PMID- 12043016
TI  - Determination of petroleum contamination in shellfish using solid phase micro
      extraction with gas chromatography-mass spectrometry.
AB  - Headspace solid phase micro-extraction (HS-SPME) has been applied as a sampling
      technique for the determination of petroleum contamination in shellfish using
      capillary gas chromatography-mass spectrometry (GC-MS). A poly(dimethylsiloxane)
      fused silica fibre (100 microm thickness) was found to be satisfactory for the
      extraction of a range of aliphatic hydrocarbons (HCs) from homogenised shellfish
      tissues. The SPME conditions, including temperature, salt content, extraction
      time and desorption temperature, were optimised for a range of aliphatic HCs (C9
      C20). A methyl silicone column GC (12 m x 0.20 mm, 0.33 microm layer thickness)
      was used with a temperature programme from 40 to 260 degrees C and the HCs were
      determined within a mass range of m/ z=50-550 in electron impact mode.
      Calibration range was from 10 to 5000 ng/g with linear correlation coefficients (
      r(2)) of 0.982 for nonane to 0.997 for octadecane. Detection limits for aliphatic
      HCs, spiked into shellfish (mussel) tissues, varied from 3.6 ng/g (tetradecane)
      to 51 ng/g (eicosane) and relative standard deviation (% RSD) values ranged from
      1.4% (hexadecane) to 24.3%(eicosane).

PMID- 12043017
TI  - Focused microwave-assisted digestion of vegetal materials for the determination
      of essential mineral nutrients.
AB  - An open focused microwave-assisted digestion procedure has been developed to
      decompose and dissolve vegetal matrices for subsequent macro- and micronutrients
      analysis. The parameters of the microwave oven were evaluated using an
      experimental design. Sulfuric acid (5 mL) and hydrogen peroxide (3 mL) were found
      to be suitable for quantitative determination of Ca, Cu, Fe, K, Mg, Mn, N, P, and
      Zn in 0.100-0.500 g of vegetal sample. The precision was better than 6% for all
      elements at different concentrations. Results for reference and laboratory
      control materials are in agreement with certified and indicative values. In
      addition, the sample digest could be used for ICP-OES of all the elements
      mentioned. The proposed microwave-assisted digestion procedure offers the ability
      to determine the most important essential plant nutrients in one unique solution
      by means of analytical techniques usually found in most laboratories.

PMID- 12043018
TI  - Competitive interaction of the antitumor drug daunorubicin and the fluorescence
      probe ethidium bromide with DNA as studied by resolving trilinear fluorescence
      data: the use of PARAFAC and its modification.
AB  - The competitive interaction with DNA of daunorubicin (DR), being present in the
      clinical anti-tumor drug daunoblastina, and the fluorescence probe ethidium
      bromide (EB) has been studied by parallel-factor analysis (PARAFAC) and full-rank
      parallel-factor analysis (FRA-PARAFAC) of a fluorescence excitation-emission
      three-way data array. The PARAFAC algorithm can furnish stable resolution results
      for the data array studied, if the estimated number of chemical components is
      consistent with the real number. The FRA-PARAFAC algorithm is not sensitive to
      the estimated number of components of the fluorescence data array if the
      estimated number is not less than the real number. Both algorithms gave identical
      resolution for the three components concerned DR, EB, and the complex EB-DNA.
      Variations of the equilibrium concentrations of free DR, EB, and the complex EB
      DNA were resolved by both algorithms. Experimental observation confirms the
      hypothesis that DR is an intercalator of DNA and that the binding interactions of
      DR and EB with DNA are a pair of parallel competitive intercalation reactions on
      same base sites of DNA. The method exemplified by this study provides a useful
      approach for studying competitive interactions of different drugs with DNA in the
      presence of interferents.

PMID- 12043019
TI  - Spectral studies of the binding of lucigenin, a bisacridinium derivative, with
      double-helix DNA.
AB  - The non-covalent binding of the cationic reagent lucigenin to DNA has been
      investigated by spectroscopic methods. Results from absorption, circular
      dichroism, and fluorescence studies revealed that lucigenin could intercalate
      into the helix of DNA. Polarization and melting studies provided further evidence
      of the intercalation binding of lucigenin with DNA. The binding constant was
      obtained by varying the DNA concentration while keeping the concentration of
      lucigenin constant. It was of the order of 10(4) mol(-1) L in DNA base pairs. The
      experiment also showed that electrostatic interaction played a significant role
      in the intercalation of lucigenin with DNA. It is suggested that lucigenin can be
      intercalated into the interior of the DNA double helix because it is initially
      attracted by the anionic DNA. This research offers a new intercalation functional
      group for DNA-targeted drug design.

PMID- 12043020
TI  - Determination of hesperidin and synephrine in Pericarpium Citri Reticulatae by
      capillary electrophoresis with electrochemical detection.
AB  - A method based on capillary electrophoresis with electrochemical detection (CE
      ED) has been developed for the determination of hesperidin (HP) and synephrine
      (SP) in the Chinese traditional herbal drug, Pericarpium Citri Reticulatae, the
      dried rind of the ripe fruits of Citrus reticulata Blanco (mandarin orange). The
      effects of some important factors such as the acidity and concentration of
      running buffer, separation voltage, and detection potential were investigated to
      determine the optimum conditions. The working electrode was a 300 microm diameter
      carbon disc electrode positioned opposite the outlet of the capillary. Both
      analytes could be well separated within 5 min in a 40 cm long capillary at a
      separation voltage of 12 kV in 50 mmol L(-1) borate buffer (pH 9.0). Excellent
      linearity was observed for the dependence of peak current on analyte
      concentration in the range from 2.5 x 10(-6) to 1.0 x 10(-3) mol L(-1) for SP and
      from 5.0 x 10(-6) to 1.0 x 10(-3) mol L(-1) for HP. The detection limits (S/N=3)
      for SP and HP were 4.96 x 10(-7) mol L(-1) and 6.54 x 10(-7) mol L(-1),
      respectively. This method has been successfully applied for the analysis of real
      samples, with satisfactory results.

PMID- 12043021
TI  - Use of a NICA-Donnan approach for analysis of proton binding to a lignocellulosic
      substrate extracted from wheat bran.
AB  - The acid-base properties of a lignocellulosic substrate extracted from wheat bran
      have been investigated. The lignocellulosic substrate was first studied by use of
      FTIR, XPS, and solid-state 13C NMR to characterize the surface-active groups.
      Major contributions arise from the presence of carboxylic and phenolic sites. The
      former are associated with long-chain fatty acids and the latter are constituent
      units of lignin. All ionizable sites were quantified by use of the Ca-acetate
      method and by potentiometric titrations in non-aqueous media. Results were
      compared with those from conductimetric titrations in water and in the presence
      of barium ions. Protometric titration curves for the lignocellulosic substrate
      were obtained at several ionic strengths. Data were also treated with the NICA
      Donnan model to determine the intrinsic ionization parameters.

PMID- 12043023
TI  - Estimation of environmental mobility of heavy metals using a sequential leaching
      of particulate material emitted from an opencast chrome mine complex.
AB  - A four-stage sequential leaching procedure was applied to assess the
      bioavailability and environmental mobility of heavy metals (Cr, Fe, Cu, Ni and
      Cd) in total suspended particulate (TSP) material emitted from an opencast chrome
      mine complex (Kemi, Northern Finland). TSP material was collected on glass fibre
      filters by a high-volume sampler, and a sequential leaching procedure was used to
      determine the distribution of heavy metals between the water-soluble fraction
      (H2O), environmentally mobile fraction (CH3COONH4), the fraction bound to
      carbonate and oxides (HONH3Cl + CH3COOH), and the fraction bound to silicates and
      organic matter, that is the environmentally immobile fraction (HNO3 + HF + HCl).
      The sequential leaching procedure was also applied to the certified reference
      materials VKI (QC Loam Soil A) and PACS-2 (Marine Sediment) to evaluate the
      accuracy and reproducibility of the leaching procedure. The heavy metals were
      determined by graphite furnace atomic absorption spectrometry (GFAAS) and flame
      atomic absorption spectrometry (FAAS). The concentrations of metals in the water
      soluble fraction (H2O) decreased in the order Fe >Cu >Cr >Ni >Cd, and in the
      environmentally mobile fraction (CH3COONH4) in the order Cu >Fe >Ni >Cr >Cd.

PMID- 12043022
TI  - Determination of Cd and Pb in food slurries by GFAAS using cryogenic grinding for
      sample preparation.
AB  - A simple method combining slurry sampling after cryogenic grinding and the use of
      a permanent modification of the integrated platform inside the transversely
      heated graphite atomizer (THGA) was proposed for the determination of Cd and Pb
      in foods. Potentialities of the cryogenic grinding were evaluated for grinding
      different materials of difficult homogenization such as high fat and high fiber
      tissues. Animal and vegetal samples were cut into small pieces and ground in
      liquid nitrogen for 2 min. Slurries were prepared directly in the autosampler cup
      after cryogenic grinding by transferring an exact amount of homogeneous powdered
      material (5-20 mg) to the cup, followed by 1.00 mL of 0.2% (v/v) HNO3 containing
      0.04% (v/v) Triton X-100 and sonication for 30 s, before transferring into the
      platform previously coated with 250 microg W and 200 microg Rh. Use of a tungsten
      carbide-rhodium permanent modifier combined with NH4H2PO4 conventional modifier
      improves tube lifetime and increases the pyrolysis temperature for Cd.
      Homogeneity tests, carried out by comparing the between- and within-batch
      precision for each kind of sample, showed no significant differences at the 95%
      confidence level, indicating good homogeneity for 5-20 mg masses. Detection
      limits were 3.3 ng g(-1) Cd and 75 ng g(-1) Pb for 1% m/v slurries. Results for
      determination of Cd and Pb in foods slurries were in agreement with those
      obtained with digested samples, since no statistical differences were found by
      the paired t-test at the 95% level.

PMID- 12043024
TI  - Quality control materials for the determination of trace elements in airborne
      particulate matter.
AB  - The development of quality control materials for the determination of selected
      trace elements in air pollution studies is described. Three types of test samples
      were prepared for proficiency testing: (1) filters loaded with PM10 fraction of
      urban air particulate matter (APM) using high-volume air samplers, which were
      subsequently divided into smaller sections, (2) a bulk sample of APM collected in
      an automobile tunnel in Prague, and (3) simulated air filters loaded with APM
      using a wet deposition process. Homogeneity of the test samples was studied using
      instrumental neutron activation analysis, proton induced X-ray emission and
      atomic absorption spectrometry, and inductively coupled plasma optical emission
      spectrometry and mass spectrometry. Sufficiently homogeneous samples were
      prepared by all three procedures. The simulated air filters appeared to be the
      most suitable test samples for proficiency testing.

PMID- 12043025
TI  - The application of ETAAS to the determination of Cr, Pb and Cd in samples taken
      during different stages of the winemaking process.
AB  - Chromium, cadmium and lead were determined in different fractions of the
      winemaking process such as in grape, pressed pomace, must deposit, deposit of
      lees, must and wine. Grape, pressed pomace, must deposit and deposit of lees were
      digested by a high-pressure microwave-assisted digestion system with a mixture of
      nitric acid and hydrogen peroxide, while for must and wine no special treatment
      was required. The temperature programs of the graphite furnace were optimised and
      different matrix modifiers were applied: Mg(NO3)2, NaVO3 for Cr and NH4H2PO4,
      Pd(NO3)2 for Pb and Cd determinations. Mg(NO3)2 and NaVO3 thermally stabilized Cr
      and enabled the increase of pyrolysis temperatures up to 1500 degrees C. NH4H2PO4
      and Pd(NO3)2 are suitable modifiers for Pb and allowed pyrolysis temperatures up
      to 800 degrees C in grape, pressed pomace and wine samples, 1100 degrees C in
      must samples and 1200 degrees C in deposit of lees. The non-specific background
      absorption of NH4H2PO4 was 1.5-2 orders of magnitude higher than that of the
      Pd(NO3)2.

PMID- 12043026
TI  - Determination of manganese in herbal medicine samples by slurry-sampling
      electrothermal atomic absorption spectrometry with a metal tube atomizer.
AB  - An ultrasonic slurry-sampling electrothermal atomic absorption spectrometry with
      a molybdenum tube atomizer has been developed for the determination of manganese
      in herbal medicine samples. Ten percent glycerol solution was used as the slurry
      medium. The optimum pyrolysis temperature was 400 degrees C. The detection limit
      was 69 fg (3xS/N). Matrix element interference was checked and it was found that
      glycerol as a chemical modifier eliminated the interference. The amounts of
      manganese in herbal medicines determined by the proposed method are in good
      accordance with those measured in dissolved acid-digested samples. The method
      enables rapid calibration, and simple and rapid analysis of manganese in herbal
      medicine samples at low cost.

PMID- 12043027
TI  - [The dynamics of infantile autism. The longitudinal studies].
AB  - 28 children diagnosed to be autistic were involved in the longitudinal studies.
      The criteria were taken from DSM-III-R. 18 children in the early stage of autism
      were chosen. The development of disorders has been observed since the period
      infancy among these children. The other group consisted of 10 children in the
      late stage of autism. The development of autism in the group was followed by
      normal development of the child until the 12-18 month of life. The research was
      conducted in the 3rd, 5th and 7th year of life. 3 areas of developments were
      taken under consideration: social relations (A), verbal vs. non-verbal
      communication (B), activity and interests (C). In the estimated group (A, B, C) 5
      criteria were achieved, each in a 5-grade scale, 1 meaning the lack of symptom
      and 5 meaning the higher intensity. At the age of 3 the intensity of disorders on
      the three evaluated areas of development did not differentiate children in early
      and late stage of autism. The future development of children in the early stage
      of autism was not successful. A visible difference was seen at the age of 5.
      Children in the late stage of autism developed in all 3 areas of investigation.
      At the age of 7, children in the late stage of autism seemed to gradually
      "withdraw from autism". Longitudinal studies conducted on autistic children
      confirmed the hypothesis about the age of child's life, when the first symptoms
      of disorders showed, as being an important predictor of the autism development
      dynamic.

PMID- 12043028
TI  - [Sense of coherence in patients of a psychiatric adolescent unit].
AB  - The sense of coherence of 72 hospitalized adolescent patients assessed by SOC 29
      was significantly lower then SOC of their siblings, mothers and fathers. SOC did
      not differentiate sensitivity subscale, which was significantly lower in a group
      of neurotic, then psychotic and eating disorders patients. SOC did not correlate
      with the number of hospitalizations. The sense of coherence of mothers of
      adolescent patients was not significantly different from SOC of mothers of
      healthy children, but SOC of patients' fathers was higher (approaching
      statistical, significance) then SOC of fathers of healthy children.

PMID- 12043029
TI  - [Family assessment measures by Manfred Cierpka].
AB  - In the first part of the paper, authors describe some research tools for the
      assessment of family functioning, concentrating mainly on self-report
      questionnaires of the family members. Advantages and methodological limitations
      of such methods are discussed. Several questionnaires of self-report type are
      described such as e.g. the Family APGAR, Family Environment Scale, Mc Master
      Family Assessment Device, as well as Family Assessment Measure (FAM) of Skinner
      and Steinhauer. Manfred Cierpka Family Assessment Measures are a modification of
      this last questionnaire. In the second part of the paper authors present in
      details Cierpka Family Assessment Measures. They describe seven dimensions of the
      family functioning such as task accomplishment, role performance, communication,
      emotionality, affective involvement, control and values and norms. Family
      Assessment Measures consist of three questionnaires such as General Scale, Dyadic
      Scale and of Self-Rating Scale. General Scale focuses on how individual member
      views the family as a whole, The Dyadic Scale assesses specific relationship
      dyads within the family and Self-Rating Scale addresses how an individual member
      views his or her functioning within the family. At the end, psychometric
      properties of these questionnaires are presented, as well as the general
      description, how they should be used in the process of the assessment of the
      family for research and in clinical practice of family therapy.

PMID- 12043030
TI  - [Some psychometric attributes of the Family Assessment Questionnaires].
AB  - In this article we present some of the more important findings from research
      aimed at the validation and normalisation of the Family Assessment Questionnaire
      (Dyadic Questionnaire, Family Questionnaire, Self-Estimation Questionnaire),
      which is the Polish adaptation of Manfred Cierpka's and Gabriele Frevert's
      "Familienboegen". In the presented study 1511 individuals from 557 families took
      part. Of these 658 individuals (including 162 children) came from 248 families
      which had no clinical health or adjustment problems, while 853 individuals
      (including 305 children) came from 309 families with problems due to
      schizophrenia, anorexia nervosa, coronary heart disease or family crisis. A new
      method of analysing raw results from the questionnaire scales was formulated and
      verified. This method was based on the criterium of sufficient satisfaction
      regarding the aspect of family life measured by the scale. The original scales of
      all the questionnaires (Task Completion, Role Performance, Communication,
      Emotionality, Affective Involvement, Control, and Values and norms) were
      characterised by average or low reliability; the general scales were
      characterised by high reliability (the Dyadic Questionnaire with very high
      reliability). As a result of factor analysis new scales were created with
      acceptable or high reliability. These were the scale of Positive statements, the
      scale of Negative statements in the dyadic and family questionnaires, and the
      scales of kindness, care and resentment in the Self-Estimation Questionnaire. The
      general scales and the factor scales generally significantly differentiated
      between the sub-samples selected due to the type of family problems present and
      relationship. On the other hand the 7 original scales did so only sporadically or
      weakly. Better results were obtained by families without health or adjustment
      problems while the worst results were obtained by families in crisis.

PMID- 12043031
TI  - [Systemic consultation--about possibilities and limitations].
AB  - The paper presents the role of systemic consultation in the diagnostic and
      therapeutic process of the people hospitalised for the first time because of a
      psychotic episode. The following questions are going to be put: What is the role
      of systemic family consultation in the diagnostic and therapeutic process on the
      inpatient ward? What are the differences between systemic consultation and others
      forms of family interventions f.e. family interviews, psycho--education, systemic
      therapy? What are possibilities and limitations of consultation? What does it
      invite to? These are only some of those questions, which are typical for daily
      clinical practice, in which the family consultation takes an important part. In
      this paper according to our clinical experience, we would like to share some of
      our thoughts on the questions put. In spite of difficulties the family
      consultation confronts us with, we are deeply convinced that it has an important
      part in therapeutic and diagnostic process.

PMID- 12043032
TI  - [Neurobiological aspects of psychotherapy theory and practice].
AB  - Psychological processes of learning may lead to biological changes in brain
      synapses, as was shown by Eric Kandel, Nobel laureate for 2000. Factors connected
      with learning (for instance, psychotherapeutic procedures) can modify the
      expression of genes occurring in brain cells. Current neurobiological research
      make it possible to explain some theoretical concepts and mechanisms of action of
      psychotherapy on the ground of basic medical sciences. Experimental and clinical
      studies point to a prominent role for early untoward life experiences in brain
      development and vulnerability for psychiatric disturbances. Neuroimaging studies
      demonstrated the existence of unconscious processes in both cognitive and
      emotional functions. In several studies, changes in brain function or in the
      biology of whole organism were measured, under the influence of psychotherapy. It
      was found that in such illnesses as depression or obsessive-compulsive disorder,
      similar changes in brain functions, as measured with neuroimaging methods, were
      observed either after pharmacotherapy or psychotherapy. The attempts have been
      also made to interpret psychotherapeutic mechanisms in the light of current
      concepts of memory processes, functioning of brain circuits or neurobiological
      theories of character and temperament.

PMID- 12043033
TI  - [Assessment of family relations by parents of patients suffering from anorexia
      nervosa--part I].
AB  - The paper presents results of research concerning the parents' perception of
      family relationships in "anorectic" families (where a daughter meets criteria of
      ICD 10) and in non-treated group. As a basic tool the Polish Version of Family
      Assessment Measure standardised on a Polish sample was used. The clinical group
      consists of 31 mothers and 32 fathers, the control group consist of 42 mothers
      and 41 fathers. The article present how parents from both groups perceived their
      marital relationship, their relationship with children, family functioning as a
      whole system and their individual functioning within the family system. The study
      revealed some interesting differences between samples. The basic conclusion is
      that perception of family relationships in the anorectic group is negative and
      incoherent in comparison with positive, congruent perception of family
      relationships in the control group. Significant differences are presented and
      discussed according to the literature.

PMID- 12043034
TI  - [Assessment of family relations by the patients suffering from anorexia nervosa-
      part II].
AB  - A lot of research indicates the importance of the family context in the
      occurrence of Eating Disorders. Authors present results of research in families
      with an adolescent suffering from Anorexia Nervosa according to ICD-10. The aim
      of this study was to examine relationships among family members. Anorectic girls
      (n = 37), their sisters (n = 16) and control girls (n = 41) completed the Polish
      version of The Family Assessment Measure standardised on a Polish sample. The
      questionnaire was constructed to measure some aspects of the family life such as
      task accomplishment, role performance, communication including affective
      expression, affective involvement, control, values and norms. The study revealed
      some interesting differences between samples. For example, anorectic girls and
      their sisters generally express dissatisfaction with the relationship with their
      parents, particularly with fathers, contrary to the control group of girls.
      Anorectic girls and their sisters more critically assess functioning of the
      family as a whole than control group girls. Anorectic girls and their sisters
      express dissatisfaction with their mutual relationship, contrary to the control
      group.

PMID- 12043035
TI  - [Some hormones secretion and personality in anorexia nervosa syndrome].
AB  - The relationship between plasma leptin, some hormones (GH, IRI, IGF-1, DHEA-S,
      LH, FSH, T, E2, TSH, fT3, fT4), glucose level, personality dispositions and
      adipose tissue content in 22 women with anorexia nervosa were evaluated. Some
      personality features as: defensiveness, domination and aggression necessities,
      high self-control, bad self-estimation, retiring, expectation of custody-
      correlated with some hormones (LH, E2, IGF-1, fT3, F, T) and leptin level. The
      ascertained relationships suggest that still unexplained causes generate
      simultaneous disturbances in the endocrine and psychic processes in central
      nervous system of anorexia nervosa patients. Probably hormonal and
      neurotransmitter derangement are the adaptive changes allowing longer survival,
      as the low leptin secretion in the severest undernutrition states is.

PMID- 12043036
TI  - [Parents of children with autism: recent research findings].
AB  - The parents of autistic children have become objects of many controversial
      studies and theories. This is a review of the studies that have been conducted in
      the nineties with this group of parents. The studies are combined into three
      categories: works on the broader phenotype, studies on the parental stress and
      the perception of the child, and finally, parents as therapists of their
      children. Although the idea of genetic determination of the cognitive, social and
      communication deficits, has been widely spread, it still has not been
      sufficiently proved. The research show that parents of children with autism
      experience profound stress. This stress response has specific profile--the most
      difficult for parents are handicaps related with atypical child behaviors, and
      the lack of knowledge about real development limitation and child problems. But
      even though, the parents supported by professionals may become the good teachers
      and therapists for their children. The partnership between parents and
      professionals is one of the conditions of the parent's success in these roles.

PMID- 12043037
TI  - [The reform of psychiatric care in Poland--2001].
AB  - Both positive and negative effects of the reform of the health care financing
      system are noted. Low prices offered by Sickness Funds for particular services (a
      bed-day, a visit) should be regarded as a negative effect of the reform.
      Particularly insufficient were the prices of services in some specialised
      psychiatric wards and in outpatient clinics. Prices in many community-based
      psychiatric facilities were also considerably underestimated. Undoubtedly, the
      reform has led to positive changes in the organization of inpatient care. These
      changes include: further reduction of beds in large hospitals organisational
      structure as well as a marked increase in the number of psychiatric wards at
      general hospitals, which should be the key units of psychiatric inpatient care.
      Increase in the number of day hospitals is another positive effect of the reform.
      The programme of psychiatric care transformation is presented mostly in the
      Mental Health Programme. The main goal of this programme is to ensure appropriate
      care for the mentally disordered people, namely comprehensive and accessible
      health care as well as other forms of help and and support necessary for living
      in family and in society. This goal will be accomplished by health care and other
      forms of help mentioned in the Mental Health Act and in the Social Help Act.
      Community-based model of psychiatric care is the key element of this system.
      Also, the Programme states desired accessibility rates for staff, number of beds
      and number of particular forms of psychiatric and alcohol treatment care.
      Separate rates for adult and children/youth population have been elaborated.

PMID- 12043038
TI  - [Physical restraint as a therapeutical procedure].
AB  - A study of 959 notices on physical restraint (Ph.R.) sent to the head of a mental
      hospital during 6 months showed that: imminent danger to the patient's own life
      or health or the life or health of others, violent destroying of ward equipment,
      grave psychomotor excitement prevail among the reasons for Ph.R. Therapeutic
      reasons are much less common. Every sixth (17%) episode of Ph.R. was used
      exclusively to perform therapeutic procedures, mainly intravenous drip. The Ph.R.
      was a therapeutic procedure is relatively seldom used without sufficient
      justification. As a rule a physician accepts nurses decision on Ph.R. with no
      further consideration. The same is true for director's acceptance of a
      physician's decision.

PMID- 12043039
TI  - [Medical services reform and changed of some patients' movement coefficients in
      psychiatric hospitals].
AB  - Selected empirical data relating psychiatric hospital morbidity from Lower
      Silesian province in the years 1998-2000 was analysed. Official statistics became
      the main source of information about occurrences and epidemiological processes,
      because of lack of population studies from the psychiatric domain. Three main
      limitations of assessing disruption of such processes were pointed: inter
      regional moving of patients; imperfection of procedures connected with
      accumulation of empirical material; influence of various administrative factors.
      These last exert essential influence on changes of patients "movement
      coefficients in hospitals during implementation of the Health Care reform in
      Poland. Number of admitted patients in general and for the first time increased,
      simultaneously time of stay in the hospital grew shorter. No reasons have been
      found, for which these observed changes would be able to have reference in real
      epidemiological processes, quality of treatment. These changes are rather caused
      by the realisation of the reform, and precisely adaptative mechanisms of the
      subjects to Health Insurances requirements.

PMID- 12043040
TI  - [Intensity of psychotic symptoms and selected demographic data as predictors of
      effectiveness of psychotherapy of schizophrenic patients in a day-hospital
      treatment].
AB  - The aim of the study was to assess the effectiveness of psychotherapy in patients
      with a diagnosis of schizophrenia in a day hospital. The presented model is based
      on the combination of group psychotherapy, individual psychotherapy and
      pharmacotherapy with respect to the individual needs of a patient. Psychotherapy
      was more effective in patients with a lower educational level and those married.
      We found that the effectiveness of psychotherapy depended on a psychopathological
      status of a patient.

PMID- 12043041
TI  - [Evaluation of clinical and psychological methods in estimating antidepressants
      efficacy in treatment of depression (preliminary report)].
AB  - The aim of the study was to evaluate the onset of action of antidepressants using
      CGI i CGI Improvement, MADRS, Self Analogue Scale and Wiener Battery Test System.
      Onset of action of antidepressants was evaluated in a group of 18 patients with
      major depression. Evaluation was assessed at 4, 8, 10, 14, 28 days of treatment.
      Significant reduction of symptoms in MADRS at day 8 was the predictor of effect
      at day 28. Reduction of symptoms in MADRS was not correlated with improvement in
      cognitive functions. Most of the psychological tests showed to be not sensitive
      enough to estimate a change in cognitive processes under pharmacotherapy.

PMID- 12043042
TI  - [Valproate in the treatment of bipolar disorder].
AB  - The paper presents the views on the use of valproate and its' derivatives in the
      treatment of mania and in the prophylactics of recurring bipolar affective
      disorder. The anti manic use of valproate has been confirmed in about half of
      those treated. Monotherapy of manic states with valproate brings about good
      results less frequently than with the use of lithium or neuroleptics. However in
      the treatment of mania, valproate is suggested equally frequent as lithium and
      carbamazepine, especially in the USA. This particularly concerns those ill in
      nonacute mania, mixed manic-depressive states, rapid cycling of manic as well as
      depressive phases--in these cases the results of treatment with valproate are
      best. Also in those where treatment with lithium proved ineffective, the addition
      of valproate can be of benefit. Valproate is also useful in the combined
      treatment with a neuroleptic. In the prevention of recurrence of bipolar
      affective disorder, the use of valproate seem to be not only equally effective as
      lithium, but also beneficial due to its' better tolerance. For the final outcome
      of the effectiveness of valproate in inhibiting recurrence, a study which would
      last longer than one year, would appear necessary. Further studies are also
      necessary in order to confirm the effectiveness of valproate in schizoaffective
      psychoses, manic patients addicted to medications or alcohol, organic disorders
      of the CNS, or the elderly patients. The more precise description of doses and
      the therapeutic concentration of the drug in the bloodstream in correlation with
      its' anti-manic and anti-recurrence action, seems to be necessary.

PMID- 12043043
TI  - [Klemens Maleszewski--the pioneer of electroshock therapy in Polish psychiatry].
AB  - On the grounds of Lithuanian and Russian archival materials unpublished so far,
      the paper presents the professional activity and psychiatric views of Klemens
      Maleszewski (1798-1873), who was the head of Vilnius's Asylum in 1837-1864. The
      time of 50s and 60s of the 19th century was a period of increasing attention
      about metallotherapy and electrotherapy. Above all, these methods were used in
      the treatment of cholera. Maleszewski conducted researches on the use of galvanic
      current and metallotherapy not only in cholera treatment, but also in the
      treatment of psychiatric disorders. He implemented successful electroshock
      therapy in a 35-year-old catatonic patient in 1861.

PMID- 12043044
TI  - [Psychiatric complications of glucocorticoid treatment].
AB  - In the article, clinical symptoms of psychiatric complications occurring during
      treatment with glucocorticoids were described, and therapeutic guidelines were
      suggested. Psychiatric symptoms are observed in approximately 25% of patients
      receiving glucocorticoid therapy. Depression, mania and mixed states are the most
      frequent, psychotic symptoms and cognitive impairments (including delirium) are
      but less frequent. Associations between clinical factors (i.e. age, sex, past
      psychiatric story, medical condition, the dose of glucocorticoids) and the
      frequency and the severity of psychiatric complications were discussed. When
      psychiatric disturbances occur, the reduction or discontinuation of
      glucocorticoids should be taken into account. Treatment of psychiatric symptoms
      is needed when psychiatric disorder is severe or the patient is suicidal or
      agitated. In such cases the use of neuroleptics, antidepressants, normothymic and
      other drugs, as well as electroconvulsive therapy was discussed. The outcome is
      generally good, the majority of patients make a good recovery, over 90% of
      patients restored to health within 6 weeks of the onset of treatment.

PMID- 12043045
TI  - [Hypothalamic-pituitary-thyroid axis in depression].
AB  - Depressed patients, although viewed as chemically euthyroid, have alterations in
      the function of hypothalamic-pituitary-thyroid axis including slight elevation of
      the serum thyroxine (T4), loss of the nocturnal TSH rise, blunted thyrotropin
      (TSH) response to thyrotropin-releasing hormone (TRH) stimulation and
      predisposition to autoimmune thyroiditis. Both hypothyroid and depressed patients
      share a number of clinical features in common. This is the reason that some
      research workers use the "brain hypothyroidism" hypothesis to explain the
      pathogenesis of depression. They suggest that depression is a state of local
      hypothyroidism in brain with normal peripheral thyroid hormone concentrations as
      a result of brain type II deiodinase inhibition and impaired transport T4 across
      the blood brain barrier. This theory seems to be compatible with the serotonin
      deficiency hypothesis of depression. Some studies confirm the existence of
      classical feedback between serotoninergic and hypothalamus-pituitary-thyroid
      systems. TRH remains under a constant inhibition by serotonin and reduced
      intracerebral serotonin concentration seen in depression will lead to increased
      TRH concentration in brain tissue. This mechanism is probably responsible for
      blunted TSH response to TRH stimulation.

PMID- 12043046
TI  - [The level of 8-iso-prostaglandin F2 alpha, 4-hydroxynonenal and malondialdehyde
      in alcohol dependent men during combined therapy].
AB  - The aim of the study was the estimation of intensity of lipid peroxidation in
      alcohol dependent male patients after three months of therapy with naltrexone or
      tianeptine and the next three months follow-up. 61 males with clinical diagnosis
      of alcohol dependence (ICD-10) have been examined. The investigated parameters
      have been determined in blood serum, the 8-iso-prostaglandin F2 alpha by means of
      immunoenzymatic assay (ELISA) and malondialdehyde with 4-hydroxynonenal by means
      of colorimetric method. In alcohol dependent men before pharmacotherapy the mean
      concentration of 8-iso-PGF2 alpha and [MDA + 4-HNE] was higher than the reference
      interval. Both, after three months of applied drugs and the next three months
      follow-up, the concentration of studied parameters decreased considerably. The
      above results show intensification of lipid peroxidation in alcohol abusers and
      advantageous influence of abstinence from alcohol and treatment of naltrexone or
      tianeptine on free-radical changes of lipids as well.

PMID- 12043047
TI  - [PAX-6 gene promoter polymorphism and other factors involved in brain atrophy in
      alcohol dependent patients].
AB  - PAX-6 gene promoter polymorphism, alcohol dependence history and CT were
      determined in the group of 68 alcoholics. We found negative correlation between
      numbers of PAX-6 gene promoter B (AC)m (AG)n repeats and atrophy of the brain and
      the cerebellum. Occurrence of these lesions was correlated with a decrease of
      alcohol tolerance, withdrawal symptoms--especially delirium tremens.

PMID- 12043048
TI  - [Triple-blind].

PMID- 12043049
TI  - [Somatization--a bad diagnosis].

PMID- 12043050
TI  - [Is alopecia areata an autoimmune disease?].

PMID- 12043051
TI  - [Hairy cell leukemia treated with cladribine].
AB  - BACKGROUND: Hairy cell leukaemia is a chronic B-cell disorder that follows an
      indolent course. Cladribine has in the last decade emerged as the drug of choice
      for treating hairy cell leukaemia. MATERIAL: We report on the long-term follow-up
      of 26 patients treated from January 1992 to June 1993 with cladribine
      administered subcutaneously. RESULTS: 25 patients were evaluable for response. 21
      patients (84%) achieved complete remission, three patients (12%) achieved partial
      remission, and one patient had no response. At a median follow-up of 6.8 years,
      24 patients (92%) were still alive. One patient died from infections four months
      after treatment, while the other patient died from a malignant melanoma 4.4 years
      after treatment. Relapse assessed by flow cytometry was diagnosed in 95% of the
      patients. 38% of those in complete and 67% of those in partial remission were
      treated by a second course of cladribine during the follow-up. Retreatment led to
      normalisation of peripheral blood count in all patients. INTERPRETATION:
      Cladribine is not a curative treatment in hairy cell leukaemia, but it induces
      long lasting remission.

PMID- 12043052
TI  - [Non-Hodgkin lymphoma in the head and neck region].
AB  - BACKGROUND: The aim of the present investigation was to describe non-Hodgkin's
      lymphoma in the head and neck region, with or without extranodal location,
      diagnosed in a regional department of otolaryngology in 1993-97. MATERIAL AND
      METHODS: Patients were identified by the Cancer Registry of Norway. Clinical data
      were obtained from patient files. Beside visible tumour the main reason for
      referral was patient complaints of symptoms from upper respiratory or
      oropharyngeal tract. Biopsy specimens were reevaluated with regard to degree of
      malignancy and related clinical staging and topographic localization of the
      lymphoma. RESULTS: 121 patients with lymphomas from Vest-Agder County (155,000
      inhabitants) were identified. In 21 of these patients (17%) the lymphoma was
      sited in the head and neck region; in 12 items extranodally located. Seven of the
      lymphomas with extranodal sites were found in pallatine tonsils and Waldeyer's
      ring. Thirteen of the 21 patients presented with a visible tumour.
      INTERPRETATION: Less than 20% of all recently discovered non-Hodgkin's lymphomas
      were located to the head and neck. Early diagnosis depends on a thorough
      otolaryngological examination and biopsies from suspected lesions.

PMID- 12043053
TI  - [Acute intermittent porphyria].
AB  - BACKGROUND: Acute intermittent porphyria is an autosomal dominant disease caused
      by a mutation in the gene coding for the porphobilinogen deaminase enzyme in the
      haem biosynthesis. The prevalence varies geographically. MATERIAL AND METHODS:
      This article presents a literature-based review of acute intermittent porphyria
      with emphasis on epidemiology and diagnostic and therapeutic strategies. RESULTS:
      The 50% reduced activity of porphobilinogen deaminase enzyme found in
      heterozygote persons is sufficient for basal conditions, but during attacks,
      stimulation of haem synthesis upstream produces toxic spillover products that
      give a purple colour to the urine. Many causes: common drugs, alcohol,
      starvation, pregnancy or menstruation, can lead to attacks of abdominal pain,
      motor and/or sensory polyneuropathy autonomic dysfunction, hyponatraemia, mental
      changes and seizures. Hepatic carcinoma may develop in older patients with acute
      intermittent porphyria. Acute attacks are treated with glucose or haem arginate
      intravenously. Preliminary results indicate a prevalence of 600/100,000 for acute
      intermittent porphyria in the municipality of Saltdal in Norway compared to 1
      2/100,000 in Europe generally. A W198X mutation is found in the porphobilinogen
      deaminase enzyme gene in members of a family in Saltdal, shared by some families
      in northern Sweden. INTERPRETATION: The high prevalence of acute intermittent
      porphyria in specific geographic areas emphasizes the importance of correct
      diagnosis, the first crucial step in avoiding attacks and associated diseases.

PMID- 12043054
TI  - [New techniques for optimization of thiopurine therapy in leukemia and
      transplantation].
AB  - BACKGROUND: The majority of chemotherapeutic agents are administered at fixed
      doses that are close to those maximally tolerated. MATERIAL AND METHODS: This
      review is based on current knowledge about the metabolism of thiopurines and the
      clinical implications of genetic polymorphism in thiopurine-S-methyltransferase
      (TPMT). RESULTS: Intracellularly thiopurines, e.g. 6-MP, are anabolized to
      cytotoxic 6-thioguanine nucleotides (6-TGN) that are incorporated into DNA and
      RNA. A competing pathway is S-methylation of 6-MP and its initial nucleotide
      metabolites by TPMT. In childhood acute lymphocytic leukaemia, high erythrocyte
      concentrations of 6-TGN correlate with the degree of leukopenia and a good
      prognosis, while low concentrations appear to be associated with higher risk of
      relapse. In most populations studied, approximately 10% have intermediate TPMT
      activity and 1/300 lacks TPMT activity due to one or two mutant TPMT alleles,
      respectively. INTERPRETATION: Phenotyping or genotyping may be used to identify
      patients as deficient or intermediate thiopurine metabolizers. This suggests that
      they should receive a profound or moderate reduction in dosage to avoid
      haematopoietic toxicity.

PMID- 12043055
TI  - [Antidote availability in Norway].
AB  - BACKGROUND: Antidotes are therapeutic substances that are used primarily to
      counteract the toxic action of poisonous agents and thus have an important role
      in the treatment of poisoning. Antidote availability is crucial for the poisoned
      patient; it is important that hospitals keep antidotes in stock to treat these
      patients. Most antidotes are expensive, infrequently used, and have short shelf
      lives. This makes hospital stocking economically difficult. In Norway, there is
      no national antidote programme. MATERIAL AND METHODS: The National Poisons
      Information Centre recently made an inquiry about antidote stocking in Norwegian
      hospitals. RESULTS AND INTERPRETATION: This survey showed that the antidote
      availability is not satisfactory. The availability of antidotes in Norwegian
      hospitals is discussed and recommendations are given.

PMID- 12043056
TI  - [Epilepsy and death].
AB  - BACKGROUND: The risk of premature death in the epilepsy population is estimated
      to be two or three times of that in the general population. Premature death is
      partly a consequence of the aetiology of the epilepsy (tumours, infections,
      cerebrovascular insults etc.), partly a direct or indirect consequence of a
      seizure: head trauma, drowning, traffic accident, suicide, status epilepticus,
      and sudden unexpected death in epilepsy (SUDEP). MATERIAL AND METHODS: On the
      basis of a review of the current literature on sudden unexpected death in
      epilepsy, we discuss incidence, risk factors and the assumed pathophysiological
      mechanisms. RESULTS: Most of these deaths are probably seizure-related. Among
      patients between 20 and 45, sudden unexpected death is the most frequently
      occurring epilepsy-related cause of death. In patients with refractory epilepsy,
      sudden unexpected death comprises about 10% of deaths; the incidence is about
      1:200-300 per year. Risk factors are symptomatic epilepsy, tonic-clonic seizures,
      early onset of the epilepsy, polytherapy, and non-compliance. Ictal central apnoe
      or ictal fatal cardioarrhythmia are probably the most plausible explanations for
      these deaths. INTERPRETATION: Some of these deaths may be prevented by better
      seizure control. Patients and their families should be given balanced information
      about this potential outcome. Family members should learn first aid and
      resuscitation.

PMID- 12043057
TI  - [Glycoprotein IIb/IIIa antagonists as antithrombotic agents].

PMID- 12043058
TI  - [Physician-patient relations in functional disorders].
AB  - The doctor-patient relationship is often problematic in relation to "functional
      disorders". A strictly biomedical understanding fails in two ways: first, because
      it does not incorporate psychosocial factors; second, because it does not take
      into account the body as a subject and carrier of meaning. A more integrated
      model would include a general understanding of the aetiology and presentation of
      symptoms (bio-psychosocial) as well as of symptoms and body as carrier of meaning
      (phenomenology). This way the patient's subjective experience, gender, social and
      cultural situation become medically valid information on par with biological
      parameters. This article describes how a bio-psychosocial and phenomenological
      understanding of symptoms can change the communication between physician and
      patient. We present some approaches that the physician may use when meeting
      patients with "functional disorders".

PMID- 12043059
TI  - [Hypochondriasis and cognitive therapy].
AB  - BACKGROUND: Hypochondriasis is an annoying disorder. Diagnostic criteria for
      primary and secondary hypochondriasis as well as comorbidity are explained.
      MATERIAL AND METHODS: Some studies of prevalence, aetiology and treatment are
      reviewed. Special emphasis is given to the cognitive model. RESULTS AND
      INTERPRETATION: The prevalence of primary hypochondriasis in population studies
      is around 1%, while the prevalence in medical outpatient clinics is 3-4.5%.
      Several controlled, clinical studies have found positive effect of cognitive
      behavioural therapy. Excessive health anxiety that is secondary to depression
      disappears when the primary disorder is treated. Controlled clinical trials of
      medication is lacking. Traditionally, hypochondriasis has been considered a
      difficult diagnosis to present to the patient and hard to treat. Research has
      increased our knowledge and understanding of the disease, and structured
      treatment protocols have led to a well founded optimism concerning prognosis.
      Central themes in the consultations are the question of life and death,
      interpretation of subjective somatic symptoms and the ability to make decisions
      when still in doubt.

PMID- 12043060
TI  - [The somatization patient in the modern society].

PMID- 12043061
TI  - [Mother-to-child transmission of HIV].

PMID- 12043062
TI  - [Guidelines concerning acute low back pain].

PMID- 12043063
TI  - [Delayed virus suppression has its price. Heart and liver are no longer secondary
      theaters].

PMID- 12043064
TI  - [Hepatotoxicity with antiretroviral therapy. The liver is affected as well].

PMID- 12043065
TI  - [Disorders of lipid and glucose metabolism. Long-term adverse effects of
      antiretroviral therapy].
AB  - In addition to readily controllable short-term side effects, highly active
      antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy
      syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance
      sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis
      remains uncertain although various hypotheses have been advanced. A number of
      approaches for the treatment of lipodystrophy are available, the effects of
      which, however, have not been confirmed by study results. Hyperlipoproteinemia
      probably means an increased cardiovascular risk, but a final pronouncement on
      this is not yet possible. Fibrates and statins are currently applied for
      treatment, but interactions with HAART medicaments have to be considered. HAART
      induced diabetes mellitus presents clinically as type 2 diabetes, and is treated
      accordingly.

PMID- 12043066
TI  - [HIV-associated lipodystrophy syndrome. Stress for the psyche and heart].
AB  - The HIV-associated lipodystrophy syndrome is a new disease entity and a result of
      the otherwise successful antiretroviral therapy. It consists of metabolic
      disorders which may in part lead to an increased cardiovascular risk or
      hyperlactatemia resulting in increased morbidity and mortality. The change in
      body shape is often disfiguring and diminishes the quality of life of the
      affected individual substantially. The present paper reviews the current options
      and limits to treat the various components of the syndrome.

PMID- 12043067
TI  - [A plea for an individualized therapy regimen. Which is the optimal dose?].

PMID- 12043068
TI  - [Promoting compliance by good advice. Practice relevant tips for managing side
      effects].

PMID- 12043069
TI  - [What is necessary besides committed research. Only a combination of measures
      will help from now on].

PMID- 12043070
TI  - [Hepatitis C and HIV coinfection. Current aspects of therapy].
AB  - HIV/HCV coinfection is characterized by a progredient course of hepatitis C. A
      more rapid development to cirrhosis, and especially in the presence of
      progredient immunodeficiency, an increased mortality due to liver failure has
      been described in coinfected patients. In addition hepatitis C has an unfavorable
      impact on the progression of HIV. The worse course of hepatitis C in HIV
      coinfected patients as well as the faster progression of HIV underline the need
      for development of treatment options for hepatitis C in HIV-coinfected patients.
      First results from trials looking at the effect of pegylated interferon and
      ribavirin for treatment of hepatitis C in HIV-coinfected patients found primary
      response rates of around 50% which were clearly better than the response rates
      observed under non-modified interferon/ribavirin therapy in HIV/HCV-coinfected
      patients so far.

PMID- 12043071
TI  - [Opportunistic diseases again on the increase? Study shows tendency for change in
      the trend].
AB  - Since the HAART, primary and secondary prophylaxis, a better understanding of HIV
      infection and, last, but not least, improved patient compliance with treatment
      due to a facilitated treatment regimen, have all contributed to achieving a
      reduction in the number of opportunistic diseases. However, they are no longer
      decreasing as rapidly as before, but appear to have leveled off. In the first
      months of HAART a so-called immune reconstitution syndrome, an acute variegated
      clinical picture may appear, which must be differentiated diagnostically from
      intolerance of HAART.

PMID- 12043072
TI  - [The effectiveness of HAART. Good planning assures long-term success].
AB  - Highly active antiretroviral therapy (HAART) leads to a reduction in the risk of
      HIV-associated disorders within a matter of months. Response to treatment and the
      permanency of optimal viral suppression, however, are clearly limited. In the
      meantime, the major factors responsible for the therapeutic effect have been
      identified. If appropriate consideration is given to these factors, effective and
      truly long-term treatment becomes possible. With foresighted treatment planning,
      an estimated 80% of the patients will experience optimal viral suppression over a
      period of at least 6 years with the currently available drugs.

PMID- 12043073
TI  - [Effective, safe and simple. The future means "once daily"].

PMID- 12043074
TI  - [Treatment of HIV infection from the neurologic viewpoint. Therapy must reach the
      brain].
AB  - An effective highly active antiretroviral therapy (HAART) can prevent the
      manifestation of HIV-1-associated encephalopathy. Also, HIV-1-associated minor
      cognitive/motor deficits--an early form of HIV-1-associated dementia--are
      improved. Clinically manifest HIV-1-associated encephalopathy is an indication
      for HAART treatment, irrespective of immune status. To date, minor cognitive
      and/or motor deficits in the presence of good immune status have not been
      identified as an indication for HAART treatment. Any CNS-effective treatment
      should be based on either zidovudine or stavudine, since these substances readily
      enter the CSF; however, NNRTI can also be applied. Side effects of HAART on the
      central and peripheral nervous system, as well as interactions with known
      neurological medicaments must be taken into account.

PMID- 12043075
TI  - [Helper cells, viral load, genetic factors, co-infections. Prognostic factors in
      HIV-1 infection].
AB  - The ideal time to initiate antiretroviral therapy in asymptomatic patients with
      chronic HIV infection remains to be defined. The most relevant laboratory
      parameter is the CD4 cell count. Therapy should be started before the CD4 cells
      drop below 200/microliter and the immune system becomes compromised. In contrast
      to past recommendations, viral load should not be used as a single laboratory
      parameter for initiation of antiretroviral therapy in asymptomatic untreated
      patients. The determination of genetic factors to assess the prognosis of HIV
      patients has not yet been incorporated into daily clinical practice. While co
      infection with GBV-C is a prognostically favorable factor for the course of the
      HIV infection, replicative hepatitis C is associated with increased mortality.

PMID- 12043076
TI  - [After 3 years no resistance development. Protease inhibitor with staying power].

PMID- 12043077
TI  - [Established and new drugs. Antiretroviral therapy 2002].
AB  - The nucleosidal reverse transcriptase inhibitors (NRTI), the protease inhibitors
      (PI) and the non-nucleosidal reverse transcriptase inhibitors remain the pillars
      of antiretroviral therapy (ART). In the spring of 2002, they were joined by a
      representative of a further class of substances, the nucleotidal reverse
      transcriptase inhibitors (NTRTI). The use of PI, but also of other substances, is
      associated with undesired effects, in particular on lipid and glucose metabolism.
      The aim of treatment is to achieve maximum reduction in the amount of virus in
      the blood. The question as to the timing of treatment--early or late--continues
      to arouse controversial discussion.

PMID- 12043078
TI  - [Nucleotide analog shows effectiveness in previously treated patients. The new
      kind of HAART].

PMID- 12043079
TI  - [No comparison with NRTI. Tenofovir is robust against resistance trouble].

PMID- 12043080
TI  - [Improving resistance profile, simplifying administration mode. New
      antiretroviral drugs].
AB  - We had some good news in the last year: Tenofovir received its FDA approval, a
      new class of antiretrovirals, the fusion-inhibitors, entered phase III trials and
      there are some promising agents in the pipeline of the pharmaceutical
      laboratories. The major issue in the development of new drugs is the
      antiretroviral activity. One of the "winners" here is TMC-125, a new NNRTI. But
      people focus also on the side-effects of the HAART, especially on long-term
      toxicity. One example is Atazanavir, a protease inhibitor which doesn't show any
      increase in cholesterin or triglycerides. But all the exciting news drugs have to
      prove their real potential in large phase III trials.

PMID- 12043081
TI  - [Current trends and research emphasis. Epidemiology, resistance testing,
      vaccination strategies].

PMID- 12043082
TI  - [Incidence of sexually transmissible diseases increases. Is prevention delegated
      to the background?].

PMID- 12043083
TI  - [European guidelines with 350 CD4 cells/microliter as the magic borderline.
      "Euro" also in HIV therapy].

PMID- 12043084
TI  - [Mobilizing the defense mechanisms of infected patients. What chance do
      immunotherapeutic approaches have?].

PMID- 12043086
TI  - [Patient-friendly therapy with long-term effectiveness. Once daily HAART is
      coming].

PMID- 12043085
TI  - [Saving on drugs, reducing side-effects. Treatment interruptions benefit acute
      and chronic HIV infected patients].
AB  - Patients with new HIV infection have been shown to benefit from therapy
      interruption. Control of the virus is better, and in some cases, further drug
      treatment can be obviated over the long term. In the case of deep-salvage
      patients, opportunistic infections may occur in some cases during the period of
      interruption. Although patients with chronic HIV infection who have already
      received lengthy periods of treatment, have no immunologic or virologic benefit
      from such interruptions, metabolic side effects are reduced, and a 20% to 50%
      drug-saving effect can be achieved. On the basis of our current knowledge, the
      question whether treatment interruption may be deleterious, for example, due to
      the development of resistance, would appear unlikely.

PMID- 12043087
TI  - [Candida infection of the skin and mucous membranes still a topic. Administering
      azoles with clinical understanding].

PMID- 12043088
TI  - [Assuring long-term success. Practicable therapy with fixed combination in a
      single tablet].

PMID- 12043089
TI  - [Thanks to automated tests. Optimized HCV therapy].

PMID- 12043090
TI  - [More transparency facilities drug choice in general practice. Booster regimens
      in direct comparison].

PMID- 12043091
TI  - [Possible cardiovascular complications. What leads to "switching"].

PMID- 12043092
TI  - [Interesting immunotherapy approach. An interferon as preload therapy].

PMID- 12043093
TI  - [First echinocandin on the market. New type of antifungal against Aspergillus &
      Co].

PMID- 12043094
TI  - [First nucleotide analog on the market. New drug for the pretreated patient].

PMID- 12043096
TI  - [Following good outcome of frequency control what has changed in therapy of
      atrial fibrillation? (interview by Dr. Ulrich Scharmer)].

PMID- 12043095
TI  - [Children and adolescents with "age-related diabetes". The number has increased
      substantially].

PMID- 12043097
TI  - [Correct nomenclature, symptom score, laboratory values and ultrasound. Your
      tools for diagnosis of benign prostatic hyperplasia syndrome].
AB  - Advances in our knowledge of prostatic disease made it necessary to amend our
      original terminology. This now takes account of the fact that the syndrome may
      differ from one patient to another, and forms the basis for the diagnostic
      approach. In particular, its intention is to show that not every patient with
      LUTS (lower urinary tract symptoms) has "BPH". The diagnostic approach to BP(H)
      (new terminology) encompasses--apart from the case history (symptom score IPSS)
      and physical examination--a laboratory work-up (among other things to exclude a
      bacterial infection, malignant tumour and renal insufficiency), uroflowmetry and
      the determination of residual urine. In proven BP(H)S ultrasonography of the
      kidneys, bladder and prostate (size) is mandatory. Conservative treatment,
      whatever form it takes, is not indicated until the diagnostic measures have been
      completed.

PMID- 12043098
TI  - [With alpha blockers, finasteride and nettle root against benign prostatic
      hyperplasia. Which patients are helped by conservative therapy?].
AB  - Symptomatic benign prostatic hyperplasia (BPH), which a man has a 50% chance of
      developing during the course of his lifetime, should receive stage-related
      treatment. While Vahlensieck stage I disease requires no therapy, stages II and
      III are indications for medication. Established medications for the treatment of
      BPH in current use are alpha-blockers, finasteride, and the phytotherapeutic
      agents pumpkin seed (cucurbitae semen), nettle root (urticae radix), the
      phytosterols contained in Hypoxis rooperi, rye pollen and the fruits of saw
      palmetto (sabalis serrulati fructus). If the patient responds, these medicaments
      can be given life-long, or intermittently. The hard criterion for the rational
      use of drug treatment of BPH is, over the long term, the reduction in the number
      of prostate operations. In stage IV disease surgical measures--after prior
      compensation of renal function--are to the fore.

PMID- 12043099
TI  - [Surgical treatment of benign prostatic hyperplasia is becoming ever more
      conservative. Soon ambulatory prostate resection?].

PMID- 12043100
TI  - [The wishes of the patient get little consideration from us. Treatment
      responsibility instead of assisted dying?].

PMID- 12043101
TI  - [Emergencies for which no one prepared you. "Heart attack" uncovered as marital
      discord].

PMID- 12043102
TI  - [New series: Diabetic autonomic neuropathy. An interdisciplinary challenge].

PMID- 12043103
TI  - [Which diagnosis--which therapy? The crux of reflux].

PMID- 12043104
TI  - On the work ethic....

PMID- 12043105
TI  - Hashimoto's thyroiditis presenting as bilateral knee arthropathy.
AB  - Hashimoto's thyroiditis is an autoimmune disease associated with antimicrosomal
      antibodies. Thyroid failure from any cause can lead to hypothyroidism which has
      numerous manifestations, including rheumatic. Rheumatic or musculoskeletal
      symptoms may be the initial presentation of hypothyroidism. A case is described
      in which knee pain was the presenting symptom in a patient with Hashimoto's
      thyroiditis without any other sign or symptom of hypothyroidism. Synovial fluid
      was non-inflammatory and lab tests were consistent with hypothyroidism secondary
      to Hashimoto's thyroiditis. The non-inflammatory arthralgia and arthritis,
      stiffness and musculoskeletal signs of hypothyroidism were completely reversible
      with adequate thyroid replacement hormone. Knee effusions are a common sign in
      hypothyroidism with a sluggish bulge sign, which is due to highly viscous
      synovial fluid. Purpose of this case is early diagnosis and treatment of
      hypothyroidism by primary care physicians, which can probably prevent many
      patients from developing polyarthritis associated with hypothyroidism.

PMID- 12043106
TI  - Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency: the case for
      screening all newborns.
AB  - Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is the most common
      inborn error of fatty acid oxidation with a frequency of 1 in 12,000, an
      estimated four new cases in the state of Oklahoma each year. The first clinical
      manifestation is a hypoglycemic episode any time between the newborn period to
      adulthood. Largely due to failure of diagnosis, the first episode can be lethal,
      with a frequency of early mortality of 25%. We report a child with MCAD
      deficiency admitted to the OU Medical Center-Children's Hospital to illustrate
      the molecular basis, clinical features, and management of the disorder and to
      present the pros and cons of instituting newborn screening in our state. Such
      screening is already part of routine newborn metabolic screening in four states.
      In Oklahoma and elsewhere, there is current discussion, which we summarize, on
      whether or not to include MCAD deficiency in the routine neonatal screening
      program. We suggest the evidence says, "Start now."

PMID- 12043107
TI  - Effect of weight loss plans on body composition and diet duration.
AB  - Are low carbohydrate high protein (LCHP) diets more effective in promoting loss
      of weight and body fat and can individuals stay on an Atkins-like diet more
      easily than on a conventional weight loss diet? A pre-test/post-test randomized
      group design composed of three cohorts was utilized to test 1) a LCHP ketogenic
      diet; 2) the Zone diet; and 3) a conventional hypocaloric diabetic exchange diet
      that supplied < 10%, 40%, and 50% of calories from carbohydrate, respectively.
      Body composition was measured before and after the intervention treatment period
      with dual energy X-ray absorptiometry. Mean weight loss was 5.1 kg for those who
      completed the 12-week program. There were no significant differences in total
      weight, fat, or lean body mass loss when compared by diet group. Attrition was
      substantial for all plans at 43%, 60%, and 36% for LCHP, Zone and conventional
      diets, respectively.

PMID- 12043108
TI  - Current treatment of cutaneous melanoma and the sentinel lymph node.

PMID- 12043109
TI  - Folic acid intake and its effects on the prevention of neural tube defects, the
      masking of vitamin B12 deficiency and the reduction of homocysteine.
AB  - The FDA's decision to require the fortification of the United State's grain
      supply with folic acid was made complex by proponents' arguments for its
      protective properties against neural tube defects (NTD) vs. opponents' concern
      regarding safety-risks in masking vitamin B12 deficiency in the elderly. Since
      this regulation mandated an effective date of January 1, 1998, research has been
      conducted to identify the impact that the fortification of 140 micrograms/100 g
      of grain in the U.S. grain supply has had on public health. Studies attempted to
      more accurately describe the minimum effective dose for prevention of NTD and to
      identify the levels at which it presents a health risk. Several studies have been
      reviewed and recommendations have been provided for altering the level of folic
      acid fortification.

PMID- 12043110
TI  - [Needles for mother and child].

PMID- 12043111
TI  - [Depression in infants and children, a clinical reality].

PMID- 12043112
TI  - [Depressive disorders in children: recognizing, caring, preventing].

PMID- 12043113
TI  - [Semeiology of children's depression].

PMID- 12043114
TI  - [When the body expresses itself].

PMID- 12043115
TI  - [Emotional security and day care admission of the small child].

PMID- 12043116
TI  - [Babies and depressed mothers].

PMID- 12043117
TI  - [Management of depressed children].

PMID- 12043118
TI  - [Psychological dimensions in a pregnancy complication service].

PMID- 12043119
TI  - [End of the Perruche legislation].

PMID- 12043120
TI  - [Reactions to the new nursing acts decree].

PMID- 12043121
TI  - [Curing children's cancers in Africa].

PMID- 12043122
TI  - [The new patients' rights, the way to use them].

PMID- 12043123
TI  - Is it dementia? Which one?
AB  - BACKGROUND: People fear losing their identity or no longer being themselves. It
      can be devastating to see someone who spent their life with you turn into someone
      who looks like your loved one but who no longer recognises you and may be
      frightened, suspicious, hostile or violent. OBJECTIVE: This article gives
      practical guidelines with a recognition, definition and differential diagnosis of
      dementia. DISCUSSION: Dementia may not be obvious to the individual, the family
      or their family doctor and should not be simply attributed to 'Alzheimer's'.
      Dementias can be confused with delirium or depression and the different dementias
      have different prognoses and different interventions.

PMID- 12043124
TI  - Alzheimer disease. Current treatment options.
AB  - BACKGROUND: In the past Alzheimer disease (AD) has been presented to elderly
      people and their families as a very frightening condition, based on media
      representation of the worst possible case scenarios. OBJECTIVE: The current
      status of pharmacological and psychosocial Intervention in Alzheimer disease is
      reviewed from the recent literature. DISCUSSION: In the last decade, the picture
      of AD has turned to one of hope and optimism as a result of advances in
      developing pharmacological and psychological management.

PMID- 12043126
TI  - S-adenosylmethionine and depression.
AB  - BACKGROUND: Depression is one on the most common psychological problems
      encountered in medical practice. Conventional antidepressants, although
      effective, have many side effects and there is a need for effective medications
      with fewer side effects. OBJECTIVE: To present all the available clinical
      evidence on the supplement, S-adenosylmethionine (SAMe) in the treatment of
      depressive symptoms as well as its safety. DISCUSSION: Recent clinical studies
      have revealed that SAMe, a naturally occurring molecule, is safe and effective in
      the treatment of mild and moderate depression. Although further research is
      required to clarify SAMe's role as a potential first line treatment for
      depression, physicians should be aware of the safety and efficacy of SAMe in
      order to advise patients on its appropriate use as complementary or as an
      alternative to traditional therapy for depression.

PMID- 12043125
TI  - Dementia. Legal issues in consent.
AB  - BACKGROUND: Doctors must generally obtain a patient's consent for a medical
      procedure before it is undertaken. When a patient has impaired mental capacity,
      the doctor may be uncertain whether the patient is competent to consent and
      decide that consent must be obtained from someone else. recent legislation gives
      legal authority to people appointed by the patient, or by the state; or a
      relative or carer, to consent (or refuse) on behalf of the patient. OBJECTIVE:
      This paper explains the general legal requirements to obtain consent; a how a
      patient's competence is assessed; and the people who may legally consent (or
      refuse) on behalf of an incompetent patient. A case study illustrates how the
      legal principles are applied in practice.

PMID- 12043127
TI  - Upper limb taping.
AB  - This is the second in the series of taping techniques for musculoskeletal
      conditions and describes taping for common upper limb problems.

PMID- 12043128
TI  - One pair must last a lifetime. Foot care and vascular disease.
AB  - This is the second in a series of articles on foot care relating to various
      clinical conditions.

PMID- 12043129
TI  - An atrophic plaque on the chest.

PMID- 12043130
TI  - Patient with a limp.
AB  - A 50 year old man, previously well, attends his general practitioner complaining
      of seven days of limping and left hip pain. Examination reveals: blood pressure
      150/85, pulse 110 and regular, temperature 37.9 degrees C. The left hip is
      irritable with decreased range of motion. The following investigations are
      arranged with subsequent results: full blood examination: white cell count 16
      (normal 4-11) with neutrophilia C-reactive protein: elevated. Left hip X-ray
      (Figure 1) shows joint space narrowing, poor definition of the articular surfaces
      and surrounding osteoporosis.

PMID- 12043131
TI  - Where is general practice heading?

PMID- 12043132
TI  - Response to 'where is general practice heading?'.

PMID- 12043133
TI  - The heroin addict! A personal view.
AB  - Heroin beckons like the sweet seductive calls of Ulysses' sirens. The alluring
      nectar of the poppy seed, once experienced is not easy to escape. The greed for
      pleasure is endless. Gratification begets gratification. This paper explores
      issues and complications of treatment intervention in heroin addiction. The
      author is a general practitioner with 25 years experience and special interest in
      substance abuse medicine.

PMID- 12043134
TI  - Wellbeing. Part 1--what is it?
AB  - This is the first in a series of articles which will explore the nondisease
      focused model of medicine--the notion of promoting wellness. The primary
      intention is to encourage the reader to reflect on their own wellbeing, and to
      gain some strategies to assist them in improving it where necessary. However, all
      the principles outlined here can also be used to help our patients in achieving
      similar outcomes.

PMID- 12043135
TI  - Enhanced primary care reforms. General practice research and leadership is
      urgently needed.

PMID- 12043136
TI  - Dementia care in general practice. What can the BEACH survey tell us?
AB  - BACKGROUND: Only a small amount of rather selective information about dementia
      care in general practice in Australia is available. AIM: To obtain a broader
      understanding of the prevalence and management of dementia in general practice.
      METHOD: An analysis of data from the Bettering the Evaluation And Care of Health
      (BEACH) study of general practice in 1998-2000 was undertaken. RESULTS: Only 21%
      of GPs reported any encounter with a patient at which dementia was treated within
      their reported 100 patient encounters. These encounters comprised only 0.43% of
      all encounters; 39% of these encounters were in a nursing home and 28% occurred
      in the GP's consulting rooms. For 7% of patients the diagnosis of dementia was
      new. Most patients with dementia were aged over 75 years, but dementia was
      treated in only 3% of all patients of this age. It was treated in 19% of patients
      seen in nursing homes. Nearly all patients (96%) with dementia had other
      conditions managed at the encounter. Medication was infrequently prescribed for
      dementia. DISCUSSION: More information is needed about dementia and its care in
      the community--its stage, extent of impairment and disability, social
      functioning, use of services, carers and their health, and progression over time.

PMID- 12043137
TI  - Health assessments of an 'at risk' population in general practice. Resource
      implications of identifying unmet health care needs--a case study.
AB  - OBJECTIVE: To estimate the resource implications associated with health care
      assessments for patients with chronic disease and those aged 75-years and over.
      SETTING: A four doctor general practice on the NSW Central Coast. METHOD:
      Examination of eligible patients according to health assessment guidelines, and
      development of health care plans where appropriate. Economic modelling of time
      and monetary resource requirements for these activities and the follow up
      management of identified health care issues. RESULTS: Eighty-four patients
      (80.8%) had a total of 181 additional health care issues identified--73 were
      geriatric specific, 32 preventive, 63 general medical and 13 of a support
      services nature. The assessments required a total of 61.5 hours (mean: 36 mins)-
      GP: 42 hours (mean: 24 mins); nurse: 20 hours (mean: 11 mins)--at a total cost to
      Medicare of $15,075 (mean: $145). Modelling of the resource requirements estimate
      a time requirement of 117.5 hours for the GP (mean: 1.1 hours), 57 hours for
      specialists (mean: 33 mins) and 140 hours for allied health providers (mean: 1.3
      hours). The costs to the community are $11,511 for the GP (mean: $111), $18,791
      for specialists (mean: $181) and $6688 for allied health care professionals
      (mean: $64). CONCLUSION: Health assessments of an 'at risk' population in general
      practice may be worthwhile. However, the resource requirements of all members of
      the health care system may be so high as to make it unsustainable.

PMID- 12043138
TI  - Usage of complementary medicine among children.
AB  - OBJECTIVE: To determine the prevalence of and parental attitudes toward the usage
      of complementary medicine among the paediatric population of a large regional
      public hospital in Victoria. Relationships between complementary medicine usage
      and sociological or medical data of the surveyed families are explored. DESIGN:
      One hundred and twenty surveys were handed out and returned from parents of
      nonsurgical inpatients of the children's ward of the Bendigo Base Hospital.
      Survey data was supplemented by information available from the hospital medical
      record. RESULTS: Thirty-three percent of respondents indicated they used
      complementary medicine for their inpatient child, and 41% for at least one of
      their children. Vitamins were more popular and acupuncture less popular than
      complementary medicine modalities used by their parents. Complementary medicine
      use was not correlated with: the patient's age; presenting complaint; duration of
      inpatient stay; or number of previous admissions. Families with children using
      complementary medicine were more likely to have skilled or professional parents
      who also used complementary medicine. There was a correlation between children
      using complementary medicine and inadequate vaccination. CONCLUSION: A
      significant proportion of children are exposed to complementary medicine. Parent,
      rather than child, characteristics were most strongly correlated with
      complementary usage.

PMID- 12043139
TI  - A Graduate Certificate and Master in General Practice Psychiatry by distance
      education--1998-2001.
AB  - BACKGROUND: The General Practice Psychiatry Program is a collaborative initiative
      between two universities and two professional colleges. Since 1998 it has offered
      general practitioners a one year part time Graduate Certificate, and a two year
      Master of General Practice Psychiatry. The learning is by distance education and
      multimode, including text packages sent out, tapes, teleconferences and two
      annual residential weekends with role plays and didactic teaching. OBJECTIVE: To
      describe the development of a Graduate Certificate and Master in General Practice
      Psychiatry. DISCUSSION: The program has been well supported with 141 general
      practitioners enrolling in the Graduate Certificate and 48 in the Masters during
      1998-2001. General practitioners have been enrolling from around Australia, with
      rural, female and more experienced GPs predominating.

PMID- 12043140
TI  - The history of the discovery of primary amoebic meningoencephalitis.
AB  - BACKGROUND: Primary amoebic meningoencephalitis was first recognised by a South
      Australian pathologist. The histopathological appearances indicated that the
      organism, Naegleria fowleri, entered the central nervous system from the nasal
      cavity via the cribriform plate. But the mode of transmission remained unknown.
      AIMS: To describe how the pathogenesis of this condition was discovered, and
      correct misinformation about the events and persons involved in this process.
      HYPOTHESIS: We hypothesised that pipeline water supplying northern centres in
      South Australia was responsible for transmitting thermophilic amoebae during the
      summer months. EVIDENCE: The evidence supporting our hypothesis was: domestic
      water pipelines were exposed to sunlight and became heated to 35-45 degrees C in
      summer which promoted the formation of vegetative forms of the amoebae; some
      patients described using tap water to flush their nasal cavities; and Naegleri
      fowleri were eventually recovered from domestic tap water supplies. CONCLUSION: A
      successful collaboration between general practitioners and laboratory scientists
      elucidated the pathogenesis of primary amoebic encephalomyelitis, a serious
      public health hazard in South Australia from 1947 until the early 1970s.

PMID- 12043141
TI  - [Aspects of Vibrio cholerae lipopolysaccharide].
AB  - In this review information on the chemical structure, biosynthesis, antigenic and
      biological properties of V. cholerae lipopolysaccharide (LPS) is presented. The
      specific structural feature of this LPS is a small size of the polysaccharide
      chain of O-antigen. In vibrios of serogroup O 139 it is oligosaccharide. The
      modification of the O-chain (methylation of individual sugars, shortened chain,
      etc.) plays an essential role in the antigenic specificity of V. cholerae LPS.
      All these factors affect of endotoxin function, the microbial resistance to
      external influences. V. cholerae LPS takes part in the formation of microcapsules
      and biofilms. The evolutional development of V. cholerae in this direction
      determines, to some extent, their increased resistance in the environment. In
      human body the heterogeneity of the LPS composition permits the preservation of
      vibrios and ensures, together with cholerogen, their pathogenetic action.

PMID- 12043142
TI  - [How poliomyelitis is to be eradicated completely].
AB  - In 1988 the World Health Assembly resolved to eradicate poliomyelitis globally by
      the year 2000. The work continues. The problem arose how to quit the system of
      mass immunization with oral poliovirus vaccine (OPV) without trouble and to
      achieve the disappearance of polioviruses worldwide. After the cessation of the
      OPV use a certain number of vaccine viruses may remain that will circulate among
      the ever growing number of nonimmune population. Live enterovirus vaccines
      prepared from nonpathogenic serotypes of ECHO virus are proposed for application
      to stop the circulation of vaccine poliovirus. These vaccines will make it
      possible to eliminate the remaining vaccine viruses from circulation and to
      complete the process of worldwide poliomyelitis eradication.

PMID- 12043143
TI  - [TT (TTV) Virus].
AB  - Characterization of TT virus (TTV), the history of its discovery, taxonomy and
      identification are reviewed as update on the diagnostics of TTV infection with
      PCR. The variability of the virus and resulting difficulties in the selection of
      a TTV DNA fragment for amplification are described. Data on the virus prevalence,
      replication and persistence are given. The pathogenetic importance of TTV is
      discussed with the account of different concepts.

PMID- 12043144
TI  - [Etiology of purulent septic diseases and the antibiotic resistance of the
      isolated causative agents].
AB  - Among the causative agents of purulent septic diseases in the surgical hospital,
      25 microbial species were isolated; of these, the prevailing species were
      Staphylococcus aureus (19.86 +/- 1.07%), Escherichia coli (16.5 +/- 0.99%) and
      Pseudomonas aeruginosa (10.06 +/- 0.8%). From environmental objects in the
      hospital 14 microbial species were isolated, among them bacteria of the genus
      Enterobacter (27 +/- 1.7%), E. coli (19.07 +/- 1.48%), S. aureus (14.7 +/-
      1.31%), Klebsiella pneumoniae (13.73 +/- 1.31%), P. aeruginosa (7.33 +/- 0.98%).
      During 3 years of observation the isolation rate of K. pneumoniae from different
      environmental objects was found to increase threefold to 24.7 +/- 2.7%. The
      results of the study of the microbial picture in surgical hospitals, as well as
      the antibiotic resistance of circulating causative agents, should be borne in
      mind while taking epidemic control measures.

PMID- 12043145
TI  - [Vibrio cholerae 01, variant eltor, in the environment].
AB  - The possibilities of the autochthonous existence of V. cholerae in open water
      reservoirs, depending on the combined effect of different biotic and abiotic
      factors are considered. The role of adaptive variability of V. cholerae O1,
      biovar eltor for its preservation in the environment is emphasized. The data on
      the duration of the V. cholerae O1 isolation from different environmental objects
      in some regions of Ukraine are presented.

PMID- 12043146
TI  - [Cholera in Kazan. Organization and implementation of cholera control
      interventions].
AB  - Data on emergent epidemiological analysis of the cholera outbreak in Kazan are
      presented. A version of the cholera focus emergence was confirmed, namely water
      route of transmission as a result of bathing in a water reservoir where sewage
      waters had penetrated. The outbreak had local and acute character. The complex of
      cholera control interventions aimed at localization and liquidation of the focus
      proved to be effective.

PMID- 12043147
TI  - [Hepatitis A in Estonia (1990-1999)].
AB  - During recent 10 years (1990-1999) essential changes occurred the epidemiology of
      viral hepatitis A (VHA) in Estonia: simultaneously with a decreased level of
      morbidity (morbidity rate per 100,000 of the population was 78.4 in 1990 and 7.7
      in 1996, or 1,241 and 112 cases, respectively), a shift in the age structure of
      patients from children of preschool age to older age groups took place. Everyday
      contacts were the main established route of VHA transmission in recent years, but
      in more than 80% of cases the risk factors of the virus transmission remained
      obscure. During the regional outbreak of VHA in North Estonia in 1998 (937 out of
      989 cases registered in the country) a rise in morbidity was observed among young
      people aged 15-29 years, when a wide spread of parenteral viral hepatitides B and
      C and drug addiction were registered in this region. During this outbreak VHA was
      transmitted mainly through everyday contacts. Still the considerable prevalence
      of injection drug users who practiced the group use of syringes and needles and
      took drugs from common containers, a sufficiently high level of the mixed forms
      of the disease (more than 18% of all registered cases of VHA), detected for the
      first time, make it possible to suggest that the parenteral transmission route
      could appear among persons belonging to the above mentioned group. Vaccination is
      regarded as the most effective measure for the prophylaxis of VHA.

PMID- 12043148
TI  - [Frequency of occurrence of Hepatitis C virus markers and risk factors among
      hospital personnel in the Novosibirsk region].
AB  - The occurrence of markers, the genotypic variety of isolates and the profile of
      risk factors with respect to viral hepatitis C among 629 employees of the
      Regional Clinical Hospital (RCH) in Novosibirsk and 1,020 employees of the
      Central District Hospital (CDH) in Iskitim were studied in a cross-sectional
      investigation. The occurrence of hepatitis C virus (HCV) markers was 5.1% in RCH
      and 2.2% in CDH. Among the risk factors in the population under study were: the
      medical history of blood transfusions (TF) with 0 TF, anti-HCV = 2.3%; 1 TF, =
      5.7% > 1 TF, = 13.5% (p < 0.001); general anesthesia (GA) with < or = 2 GA, anti
      HCV = 2.8%; > 2 GA, = 7.8% (p = 0.002); surgical interventions (SU) with 0 SU, =
      1.9%; > 0 SU, = 4.3% (p = 0.012); the intravenous use of drugs (OR = 31.8); age
      (< or = 25 years, anti-HCV IgG = 8.6% > 25 years, = 4.5%); the number of partners
      of the opposite sex < or = 4 partners, = 2.4%; > 4 partners, = 6.9%; p < 0.001).
      The probable risk factors at a working place (pricks and cuts, contamination of
      mucous membranes with blood and other biological fluids, etc.) proved to be
      faintly related with the status of HBV infection. HBV isolates detected in the
      examined persons (35 examinees) were distributed by genotypes as follows: 60% of
      subtype 1b, 28.6% of subtype 2a/2c, 11.4% of subtype 3a. HBV of genotype 1a was
      not detected in the examined specimens, while the detection rate of genotype
      2a/2c was considerably greater than in specimens obtained in the European and
      Asian parts of Russia (according to the data reported earlier).

PMID- 12043149
TI  - [Characterization of Vibrio cholerae eltor in the city of Kazan in 2001].
AB  - Information on V. cholerae eltor isolated in the focus of cholera in Kazan in
      2001 at different periods of the outbreak is presented. The identity of strains
      isolated from patients, vibriocarriers and environmental objects, including their
      antibioticograms (sensitivity to cyprofloxacin and resistance to trimethoprim-
      sulfamethoxazole, streptomycin, furazolidone and nalidixic acid, which may be
      regarded as markers), is shown. Variable tandem repetitions in the DNA of 30
      isolates strains of different origin have been determined. The results of this
      determination make it possible to classify all these strains as one genotype,
      which confirms the suggestion on the circulation of one subclone of the infective
      agent of cholera in the focus. As revealed in this investigation, the isolated
      strains are labile with respect to diagnostic phage eltor, while ctx+ strains are
      resistant to phage eltor ctx+.

PMID- 12043151
TI  - [Antibodies to iron-regulated proteins of meningococci in blood sera of healthy
      persons of different age groups].
AB  - One hundred and twenty individual sera obtained from healthy persons of different
      age groups were studied for the presence of antibodies to meningococcal iron
      regulated proteins (IRP). The study revealed that occurrence of such antibodies
      in sera under study was IRP nature- and age-dependent. Antibodies to two IRP were
      found to occur most frequently: 85 kD (TbpB) and 72 kD (FrpB). Antibodies to the
      former IRP were detected in more than 50% and antibodies to the latter IRP, in
      more than 90% of sera. This was probably due to the presence of epitopes common
      with those in protein antigens of some other microorganisms, such as Moraxella
      catarrhalis and Haemophilus influenzae. The occurrence of antibodies to
      periplasmatic IRP with 34 kD (FbpA) in blood sera varied within the range of 5 to
      30%. At the same time the occurrence of antibodies to this protein in the sera
      under study was age-depended: children until five years exhibited the minimal
      occurrence (about 5%), while in adults it reached 30%.

PMID- 12043150
TI  - [Evaluation of the immunological activity and safety of group B meningococcal
      vaccine prepared from a natural complex of specific polysaccharide and outer
      membrane proteins].
AB  - Immunological activity and safety of group B meningococcal vaccine prepared from
      a natural complex of specific polysaccharide and outer membrane proteins were
      under study. The immunological safety of the vaccine was evaluated by the absence
      of antibodies to denaturated and native DNA (d-DNA and n-DNA). As shown with the
      use of the enzyme immunoassay (EIA), the administration of the vaccine did not
      induce antibody formation to d-DNA and n-DNA during the observation period. The
      titer of bactericidal antibodies in the immune bacteriolysis assay (IBA) to the
      vaccine strain B:2b:P1.2 after immunization increased four-fold and greater in
      80% of the vaccinated persons. The significant increase of bactericidal
      antibodies to heterologous strains B:2a:P1.2 and B:15:P1.7 was registered in 20
      30% of the vaccinees, respectively. A month after the repeated vaccination an
      increase in specific IgG antibodies to the complex antigen was found to occur
      according to EIA results. The use of RIB made it possible to evaluate the
      preventive activity of group B meningococcal vaccine as a whole and to suppose
      that the vaccine induced mainly type-specific response.

PMID- 12043152
TI  - [Characterization of the immune status of patients with vaccine-associated
      poliomyelitis].
AB  - Specific humoral immunity, total immune status and typing of HLA antigens, class
      1, in loci A and B were studied in children with vaccine-associated paralytic
      poliomyelitis (VAPP). The immune status investigation revealed that changes in
      the content of serum immunoglobulins were most frequent. Out of 8 examined
      children, 5 children had IgA deficiency and 1 child had total variable
      immunodeficiency. In one case disturbances in cell-mediated immunity prevailed.
      Tissue typing revealed the presence of HLA A2 and B44 in 5 out of 6 examined
      children, which considerably exceeded their average occurrence among the
      Belorussian population. In spite of frequent detection of immunological
      disturbances in VAPP patients, out of 38 serologically examined children 36 (95%)
      were found to have virus-neutralizing serum antibodies to poliovirus, which was
      indicative of the capacity of their immune system for response to the
      administration of vaccine virus. To minimize the risk of VAPP in children and to
      achieve the goal of poliomyelitis eradication the combined immunization scheme
      consisting of 1-3 vaccinations with inactivated poliovaccine with subsequent
      administration of oral vaccine prepared from attenuated Sabin viruses is regarded
      as most promising.

PMID- 12043153
TI  - [Cholera toxin as Vibrio cholera superantigen].
AB  - Experimental data confirming our earlier suggestion, that cholerae toxin (CT)
      possesses superantigen (SA) properties are presented. When used in very small
      doses, CT has been found to induce polyclonal activation of T lymphocytes,
      essentially exceeding that observed in classical T mitogens characteristic of SA.
      CT, in contrast to mitogens and similarly to other SA, is shown to display this
      activity only in the presence of antigen-presenting cells. Experiments with the
      use of monoclonal antibodies to the variable region of the beta-chain of the T
      cell receptor (V beta TCR) have demonstrated that CT, similarly to other SA, are
      capable of inducing expression of certain types of V beta TCR and causing
      polyclonal activation of T lymphocytes carrying these types of V beta TCR. The
      presence of these properties gives grounds for regarding CT as SA. The SA
      activity of CT has been found to be linked with its subunit A.

PMID- 12043154
TI  - [Role of HLA phenotype in the formation of chronic hepatitis C virus infection].
AB  - Clinical, biochemical and immunological parameters depending on HLA-phenotypic
      features were examined in 107 patients aged 18-78 years with chronic hepatitis C
      virus (HCV) infection. Clinical and biochemical manifestations (asthenic, pain
      and cytolytic syndromes, hepatomegalia, hyperbilirubinemia, hypoprothrombin- and
      proteinemia), observed in hepatitis C, were more pronounced in patients having
      HLA-A30, B35, B41, Cw2, A1-B35, A9-B8. The carriers of B8 and B35 antigens were
      found to have inadequate immune response in HCV infection, manifested by
      progressive chronic process in the liver and the development of cirrhosis in
      patients with such specificity.

PMID- 12043155
TI  - [Mechanisms of high sensitivity of Mongolian pika spp. (Pallas) to Yersinia
      pestis].
AB  - The regularities of the infectious process of plague in a sensible Pallas' pika
      species, are presented. The specific infectious process was shown to pass a
      number of phases. These phases are characterized by certain changes in the
      composition of the leukocytic pool of the peripheral blood, the immune system and
      the activity of the bactericidal systems of professional phagocytes. The
      infectious process in sensitive animals is accompanied by the formation of
      secondary relative immunodeficiency with a pronounced hypersuppressive component,
      which leads to disturbances in the cooperative interaction of immunocompetent
      cells; in its turn, it results in dysbalance in the cytokine system and, as a
      consequence, to irreversible disturbances in homeostasis, leading to the death of
      the infected animal.

PMID- 12043156
TI  - [Diversity within a population of Shigella sonnei according to markers of
      medicinal preparations].
AB  - As revealed in this study, S. sonnei population is represented by two clusters
      with respect to the sensitivity to different antibiotics. A higher degree of
      diversity was observed with respect to the action of streptomycin, kefzol,
      ampicillin, chloramphenicol and kanamycin in comparison with the action of
      gentamicin, nevigramon, rafampicin, tetracycline and polymyxin. The level of
      diversity of S. sonnei with respect to the sensitivity to antibiotics under study
      underwent essential changes during the calendar year. The distributions obtained
      study quite closely corresponded to changes in Sonne dysentery morbidity observed
      within the year period: the first cluster corresponded to the period of morbidity
      between the seasons and the second one, to the seasonal period of morbidity. The
      minimal coefficient of diversity fell on May while the maximum--on September. The
      minimal level of S. sonnei diversity, as a rule, corresponds to the minimum
      biosystems stability.

PMID- 12043157
TI  - [Comparative efficacy of laboratory methods for cytomegalovirus detection in
      autopsy material].
AB  - Eighty eight autopsy specimens obtained from 30 fetuses, still-borns and infants
      died during the first year of life, all suspected for congenital virus infection
      at postmortem examination, were studied. The specimens were analyzed by 3
      techniques: rapid culture method (RCM) for detection of cytomegalovirus (CMV)
      infectious activity, the immunocytochemical method for detection of CMV antigen
      in prints of organs and polymerase chain reaction (PCR) for detection CMV DNA.
      CMV was detected in 16 out of 26 specimens (61.5%) by PCR, in 43 out of 88
      specimens (49%) by RCM and in 15 out of 64 specimens (23%) in prints. The
      comparison of immune reagents revealed that monoclonal antibodies (McAb) were
      more specific than polyclonal serum antibodies, as the latter yielded the
      positive reaction in 10 out of 26 cases (38%), found to be negative in PCR. The
      data thus obtained indicate that complex techniques, including PCR and RCM in
      combination with McAb, should be used for evaluation of CMV infection role in
      child mortality.

PMID- 12043158
TI  - [Level of serum tumor necrosis factor-alpha and the degree of liver fibrosis in
      children with chronic viral hepatitis B, C and B+C, treated with interferon
      alpha].
AB  - Children with chronic virus hepatitis B and C, as well as combined chronic virus
      hepatitis B + C, were found to have a higher level of tumor necrosis factor-alpha
      (TNF-alpha) in their serum than healthy children. Complete clinical and
      virological response to treatment with interferon-alpha is accompanied by a
      decreased inflammation and fibrosis of the liver, as well as by a decreased level
      of TNF-alpha, in comparison with nonresponsive patients. Positive correlation
      between the level of TNF-alpha and the degree of liver fibrosis in sick children
      was noted.

PMID- 12043159
TI  - [Microflora of the inflammatory erosive areas of the esophagus in esophagitis
      patients].
AB  - Seven patients with erosive esophagitis and reflux esophagitis were examined. In
      cases of inflammatory erosive phenomena staphylococci, Micrococcus luteus,
      Candida, bacteria of the genera Pseudomonas, Veilonella, Klebsiella and other
      bacteria of the family Enterobacteriaceae, as well as Helicobacter pylori were
      detected in different frequency. In most cases concentrations of microorganisms
      were 4.07-5.39 Ig CFU/g. Isolated microorganisms producing different
      pathogenicity enzymes--hemolysin (Streptococcus intermedius, S. sanguis,
      Staphylococcus saprophyticus, S. warneri, Bacteroides spp.), lecithinase
      (Staphylococcus xylosus), caseinase, RNAase and catalase--were detected.

PMID- 12043160
TI  - [Dynamics of growth of Haemophilus influenzae serotype B and synthesis of
      capsular polysaccharide in the process of cultivation in a synthetic nutrient
      medium].
AB  - The dynamics of H. influenzae, serotype b, growth and synthesis of their capsular
      polysaccharide in the synthetic nutrient medium, proposed by Herriot for
      noncapsular strains, was studied using 6 strains. The growth rate of H.
      influenzae, serotype b, and the amount of capsular polysaccharide, synthesized in
      the above mentioned medium, practically were not different from those in heart
      brain broth (Difco). The possibility of minimizing the composition of Herriot's
      medium without any adverse effect on the amount of synthesized capsular
      polysaccharide was shown. As the result of these studies, the expediency of the
      cultivation of H. influenzae, serotype b, in the synthetic medium, intended for
      obtaining the preparations of capsular polysaccharide, was proved.

PMID- 12043162
TI  - [Diphtheria in the Republic of North Ossetia (Alania)].
AB  - The present epidemiological situation in diphtheria in the Republic of North
      Ossetia (Alania) is analyzed. The data on diphtheria morbidity and lethality are
      given. The present stable situation resulted from mass immunization of the adult
      population which ensured the level of vaccination coverage reaching 87% in 1995.

PMID- 12043161
TI  - [Clinical and morphological aspects of shigellosis flexneri in patients with an
      aggravated premorbid state].
AB  - The analysis of 10 fatal outcomes in patients with acute shigellosis during the
      period of 1999-2000 made it possible to find out that most of deceased
      shigellosis patients belonged to the group inclined to alcohol abuse and having
      initial alimentary disturbances. In 6 cases of acute shigellosis with fatal
      outcome the causative agent was S. flexneri 2a, in 2 cases--S. flexneri 3a, in 1-
      S. flexneri 4b. The main cause of fatal outcomes was accompanying double
      pneumonia. Lesions of the intestinal tract in deceased shigellosis patients were
      of destructive character, resulting, in a number of cases, in serous and
      perforative peritonitis.

PMID- 12043163
TI  - [Opportunistic bacteria detected in cultivated mussels].
AB  - As many as 8 Listeria monocytogenes strains, 12 Pseudomonas aeruginosa strains
      and 5 Staphylococcus aureus strains were isolated from mussels Mytilus edulis,
      grown on special installations in the Trinity Bay of the Gulf of Peter the Great,
      the Sea of Japan. The isolated cultures proved to be highly resistant to a number
      of antibiotics. Many strains displayed DNAase and haemolytic activity. The
      cultures of L. monocytogenes, S. aureus and P. aeruginosa also had high lipase,
      protease and lecithinase activity. The organism of the mussels seems to be a
      confinement for these bacteria under study.

PMID- 12043164
TI  - [Detection of the endotoxin of Gram-negative bacteria in human blood].
AB  - Recent new data on the important role played by lipopolysaccharides (endotoxin)
      of Gram negative bacteria in physiology and pathogenesis of the most important
      human infectious and noninfectious diseases testify to the necessity of wide
      clinical trials of different methods for LPS detection in blood and other
      physiological fluids. Among presently available diagnostic methods for
      endotoxinemia detection, the highly sensitive LAL (Limulus Amebocyte Lysate) test
      in various modifications is most widely used. The LAL test is known to be non
      specific, however many drawbacks of this test have been successfully overcome.
      The results of clinical studies on the determination of the LPS activity in the
      systemic blood stream and antibody titers to its most common determinants, as
      well as the reserves of endotoxin binding with granulocytes give grounds for
      optimistic evaluation of the future studies on the role of LPS in human
      physiology and pathology. In clinical practice both positive sides and drawbacks
      of the presently known methods for LPS detection, including the LAL test, must be
      borne in mind for the complex evaluation of endotoxinemia levels.

PMID- 12043165
TI  - [Some mechanisms of Helicobacter pylori persistence].
AB  - The mechanisms of the pathogenesis of Helicobacter pylori infection, ensuring the
      prolonged survival of these bacteria in the aggressive medium (gastric mucosa),
      are considered. A new approach to the systematization of the mechanisms of H.
      pylori persistence is proposed: the mechanisms ensuring the stability of H.
      pylori in the presence of aggressive physical and chemical factors, the
      mechanisms ensuring antagonistic effects in biocenosis and the mechanisms
      ensuring resistance to the protective factors of the host. Data on the
      persistence potential of H. pylori in accordance with the proposed classification
      are presented.

PMID- 12043166
TI  - [Viability and virulence of Francisella tularensis subsp. Holarctica in water
      ecosystems (experimental study)].
AB  - Under conditions of artificial water biocenosis a virulent strain of F.
      tularensis could be detected in fresh water shrimps and mollusks for about a
      month, in Conepoda for up to 20 days and in Chydorus sphaericus for up to 7 days
      from the moment of the aquaria water contamination. In silt F. tularensis could
      be detected for a longer period (up to 2 months). Daphnia, Oligochaeta and C.
      sphaericus appeared to be unfavorable environment for this microorganism. The
      virulence level of F. tularensis microbial cells decreased in paralell with
      prolongation of their stay in water biocenosis. The presence of water biota
      favours F. tularensis preservation in water reservoirs for a longer time.

PMID- 12043167
TI  - [Superantigens of Group A Streptococcus].
AB  - In this review the superantigens (SAG) of group A Streptococcus, mainly pyrogenic
      toxins, and the coding genes are characterized. Specific sites on the molecules
      of the main histocompatibility complex, class II, and T-receptors, interacting
      with SAG, are described. This interaction results in hyperproduction of cytokines
      posing a systemic influence and leading to severe consequences. The data on the
      state of protective immunity in SAG-associated diseases and some approaches to
      their treatment are given.

PMID- 12043168
TI  - Got the bear market blues? Knowledge can turn fear into opportunity!
AB  - The current bear market with its economic hardships was predictable. The previous
      bull market, a seemingly never-ending bounty, brought us unrealistic
      expectations. Simply put, it spoiled us. How much did you or your advisors have
      to know to do well in that market? How many gurus were there? How many are there
      now? For the experienced and the inexperienced investor, these are worrisome
      times. However, just as the seasons and tides ebb and flow, we are surely going
      to see another bull market. It is expected that the market should retrace at
      least 50%. Remember that in the bear markets of 1929, 1974 and 1987, a 50%
      retracement ensued followed by lengthy bull markets. Also recall that bull
      markets are of much lengthier duration than bear markets. The most important
      thing to remember, according to Mark Twain, is that "Courage is resistance to
      fear, mastery of fear, but not the absence of fear." Do not panic! Knowledge
      gained from this article and others in the investment arena should give you a
      sense of direction, confidence in your decisions and some control over your
      financial future. In the long run, staying in the market has always proved to be
      the best choice (see Table 1). Most important, now is the time to educate
      yourself so that you can become proactive in making investment decisions or at
      least evaluate your financial advisor's investment choices. Start now; it's
      easier than you think!

PMID- 12043169
TI  - Transition from childhood to adulthood.

PMID- 12043170
TI  - Aging in individuals with lifelong disabilities.
AB  - The major research data and findings related to aging among persons with
      developmental disabilities are discussed. Differences between the aging processes
      noted in the general population and individuals who have developmental
      disabilities are highlighted. Topics addressed include prevalence of
      developmental disabilities and mortality rates for individuals with developmental
      disabilities. The effects of aging on the senses, the neuromusculoskeletal
      system, and the cardiopulmonary system are presented along with the clinical
      implications of these changes in individuals with developmental disabilities who
      are aging.

PMID- 12043171
TI  - A qualitative study of the transition to adulthood for youth with physical
      disabilities.
AB  - The purpose of this qualitative study was to explore the experiences,
      perceptions, and needs of youth with physical disabilities in transition from
      adolescence to adulthood. Purposeful sampling strategies were used to select 34
      study participants who lived in three regions of south-central Ontario, Canada.
      Data collection methods were individual and focus group interviews, and were
      guided by a set of open-ended questions. An editing style of analysis sorted the
      text into codes for description and interpretation. Themes emerged about context,
      the transition process, needs, and services. Participants identified a poor fit
      between young persons with disabilities and the adult world they were entering.
      They recommended that services be focused on environmental supports to enable
      them to "build their own bridges" to the adult world. Community-based transition
      services need to be planned in collaboration with youth with disabilities and
      their parents. Concepts of person-environment fit and health promotion can be
      incorporated into services to enable young persons with disabilities to
      experience a smooth transition from adolescence to adulthood.

PMID- 12043172
TI  - Secondary conditions of the musculoskeletal system in adolescents and adults with
      cerebral palsy.
AB  - Cerebral palsy (CP) is a disability that affects individuals throughout their
      lifespan. Adolescents and adults with CP are at risk for many secondary
      conditions that cause a loss of function and deterioration of quality of life.
      This article presents a review of the literature of musculoskeletal conditions of
      people with CP that can develop or worsen across the lifespan as a consequence of
      the primary neuromotor impairments. Health care behaviors of adolescents and
      adults with CP are discussed and their impact on secondary conditions is
      examined. Suggestions for how pediatric occupational therapists and physical
      therapists can assist children and adolescents to take responsibility for their
      own health and wellbeing are presented. Lastly, occupational therapists and
      physical therapists are encouraged to take responsibility for treating
      musculoskeletal impairments and disabilities in adults with CP.

PMID- 12043173
TI  - Aging adult children with developmental disabilities and their families:
      challenges for occupational therapists and physical therapists.
AB  - The purpose of this article was to review the literature about families of adult
      children with developmental disabilities, the impact of culture on access to
      health care services, and community-based health care services for adults with
      developmental disabilities to answer the following questions: (1) How do parents
      of adult children with mental retardation and other developmental disabilities
      describe their caregiving experiences?, (2) What are frequently identified unmet
      service needs by the parents/families?, (3) Does the family's culture or ethnic
      background influence how they view their caregiving experiences?, and (4) What
      are the unique challenges facing families when attempting to access health care
      services? Currently little information exists about the needs of parents and
      other family members who live with adults with developmental disabilities.
      Longitudinal studies and studies to assess the influence of culture on care
      giving are especially needed. Therapists need to use approaches that will empower
      children and their families so they can better meet their current challenges and
      provide a foundation for the skills they will need to meet future challenges as
      adults.

PMID- 12043174
TI  - Web sites related to methods for evaluating Web sites.

PMID- 12043175
TI  - [A review of intervention studies for prevention of falls in older people].
AB  - Falls are a well-known cause of hip fracture leading to hospitalization and
      bedridden status among older people. Intervention programs for prevention of
      falls in the elderly may therefor have considerable benefits in reducing
      disability and health care costs. The available literature on intervention
      programs to prevent falls by older people was here reviewed, using the Medline
      and Japana Centra Revuo Medicina databases for 1990 to 2000. The strategy used
      for the search was "falls of accident falls, intervention or intervention study,
      and cost or cost-effectiveness". Various types of interventions targeting both
      community dwelling and institutionalized elderly have been reported from western
      countries: home modification, exercise programs, and medical and behavioral
      interventions individualized according to the person's risk factors. Many
      internal and external risk factors of falls have been identified, and it has been
      proven that interventions to reduce these risk factors lower the incidence of
      falls and are cost-effective. Programs and services for the prevention of falls
      have been carried out in different regions of Japan, but few reports evaluated
      their effectiveness. Further implementation of falls prevention program should be
      accompanied by promotion of research in the efficacy area in Japan.

PMID- 12043176
TI  - [Effects of social support on the mental health of mothers with infants].
AB  - OBJECTIVE: We surmised that increase in stress in mothers having infants might be
      due to decline of social support under circumstances where nuclear family
      households now predominate. The present study was therefore conducted to analyze
      relations between stress reactions of mothers having infants, their recognition
      of social support, and negative feelings toward their baby and child care, a
      major factor in the burden of childcare. METHODS: The subject were 909 mothers
      having infants in nuclear families who lived in I city in Osaka Prefecture.
      Health examinations of infants at the ages of 4 months, 1 year and 6 months, and
      3 years and 6 months were utilized. Questionnaires titled "Survey on Childcare"
      were distributed in advance by mail to parents of the infants included in the
      health examinations and collected at the health examinations. The survey period
      was August to September 2000. Personal background variables and, psychological
      investigation items, including mental health in terms of stress reactions,
      negative feelings toward childcare as a factor in the burden of childcare, and a
      support network scale were surveyed and analyzed. RESULTS: The mothers with
      infants were judged to be in a stressful state from the average mental health
      scores in all groups. Multiparas had significantly higher negative feelings
      toward childcare scores. Regarding the age groups of children, a significantly
      decreasing recognition of a support network as well as significantly increasing
      negative feelings toward childcare were observed with the growth of children.
      There was a positive correlation between negative feelings toward childcare and
      stress reactions. The recognition of social support was negatively correlated
      with stress reactions and negative feelings toward childcare. CONCLUSION: The
      study revealed that mothers having infants are in a stressful state and that the
      recognition of stress is related to negative feelings toward childcare and the
      recognition of a support network. The feeling of sufficient support lowers the
      level of stress arising from childcare, and facilitates avoiding or coping with
      problems, thereby promoting mothers' physical and mental health. This is
      important for continuation and fulfillment of childcare.

PMID- 12043177
TI  - [An analysis of the length and costs of respirator use with observational data
      based on medical records].
AB  - OBJECTIVE: This paper documents an analysis of the impact of respirator use on
      medical expenses with observational data based on medical records from all over
      Japan. METHOD: The data set included records of medical procedures during a
      single month, but not for procedures and information extending over plural
      months. Accordingly, censoring was an important problem. To overcome this,
      samples are classified into four groups; complete, right censoring, left
      censoring and both censoring ones using length of respirator use and hospital
      stay. Then, the Gompertz model was applied to calculate the expected length of
      respirator use. Simultaneously, medical expenses for respirator use were also
      estimated. RESULTS: The estimated expected length of respirator use was from 10
      to 104 days, with expected medical expenses per case of from 30,000 to 40,000 yen
      and the number of respirator usages on aggregate of 5510. CONCLUSIONS: This means
      the impact of respirator use on medical expenses is from 18 to 250 billion yen
      per year.

PMID- 12043178
TI  - [Relationship between intake of sweet drinks and candies and oral health status
      in the adult population].
AB  - PURPOSE: The purpose of the study was to examine the relationship between intake
      of sweets (sweet drinks/candies of chewing gum) and oral health status, while
      adjusting for age and other dental health behavior. METHODS: The data used were
      based on a cross-sectional study regarding dental checkup of a worksite. Of a
      total of 7,713 workers, 5,232 (67.8%) participated in the dental checkup. From
      this population, data for only 5,034 were analyzed. The dental checkup included a
      self-reported questionnaire and oral examination by a dentist. The oral health
      status variables were the CPITN score, missing teeth/filled teeth/decayed teeth,
      and self-reported gum bleeding. We used multiple logistic regression to calculate
      odds ration (OR) and 95% confidence interval (95% CI) for each oral health status
      according to intake of sweets. RESULTS: Among males, subjects who took sweet
      drinks almost every day, compared to subjects who hardly took, had higher risk of
      missing teeth (OR = 1.4; 95% CI: 1.2-1.7), filled teeth (OR = 1.7; 95% CI: 1.4
      2.0) and gum bleeding (OR = 1.5; 95% CI: 1.2-1.8). Dose response relationships
      were also observed between intake of sweet drinks and these variables. No
      significant association was recognized between intake of candies of chewing gum
      and oral health status. CONCLUSIONS: The results indicated that intake of sweet
      drinks is a determinant of oral health status, independent of dental health
      behavior, particularly among males.

PMID- 12043179
TI  - [Effects of nutrition education for residents on intake of lipid-related
      nutrients].
AB  - OBJECTIVES: Health education for residents is now common, but only a few studies
      of its effects have been made. The purpose of this study was to investigate the
      effects of nutrition education for residents on intake of lipid-related
      nutrients. METHODS: A total of 79 females (40-64 years) who underwent a health
      examination for residents in a town, Nara Prefecture and were found to have total
      serum cholesterol levels between 220 mg/dl and 300 mg/dl were divided into two
      groups. In the first group, nutrition education was performed during the first 24
      weeks and no education was performed during the second 24 weeks as the self
      control period. In the second group, no education was given during the first 24
      weeks as the waiting period but was performed during the second 24 weeks. During
      the education period, dietary intervention for individual subjects was performed
      3 times at intervals of 8 weeks by trained dietitians. The intake of nutrients
      was estimated by the food frequency questionnaire developed by Ueshima and
      Okayama, and changes in the intake of nutrients adjusted for total energy were
      used for evaluation of the effects of the education. RESULTS: In the first group
      of 42 subjects, three discontinued during the education period and two during the
      self-control period, and in the second group of the 37 subjects, six discontinued
      during the waiting period and three during the education period. At the end of
      the education period, for the total of 67 subjects (39 and 28 in the first and
      second groups, respectively), the total energy adjusted intake of lipid,
      cholesterol and saturated fatty acid were significantly lower and the PS ratio
      was significantly higher than in the second group during the waiting period.
      During the self-control period after the education, the adjusted intake of lipid
      related nutrients remained unchanged in the 37 subjects of the first group who
      had been given the nutrition education in the first 24 weeks, and it was
      significantly lower at the end of the 48-week test period than at the baseline
      examination. The percentage of the subjects showing a desirable intake pattern of
      major lipid-related nutrients increased significantly after the education period.
      CONCLUSIONS: These results indicate that the intake of lipid-related nutrients
      can be decreased by educating individual subjects about nutrition and the effects
      are maintained for at least 24 weeks.

PMID- 12043180
TI  - [The prevalence of iron deficiency anemia among 6- to 18-month-old children in
      Japan].
AB  - BACKGROUND: Iron deficiency anemia is one of the treatable causes of
      developmental delay in infants and is therefore screened in several countries.
      However, in Japan, a screening program for anemia among infants has not been
      introduced and data on the prevalence of iron deficiency anemia and results of
      therapeutic trial with iron supplementation are limited. OBJECTIVE: To examine
      the prevalence of anemia, diagnosis was made with venipuncture blood and iron
      deficiency anemia was confirmed in a therapeutic trial of infants in Japanese
      communities. PARTICIPANTS: Six- to 18-month-old infants participated in the
      anemia screening program in Shinshiro city and Shitara districts, Aichi, and
      Fujisawa town, Iwate, Japan. METHODS: Capillary blood samples in microtubes were
      obtained by skin puncture, and centrifuged to measure the hematocrit. When the
      value was low, venipuncture blood was examined. A hemoglobin concentration under
      11 g/dl was judged as a positive result. Anemic infants were referred to
      pediatrics for prescription of ferrous sulfate. Iron deficiency anemia was
      defined as a hemoglobin concentration elevated by 1 g/dl or more with a 4-week
      regimen of ferrous sulfate (therapeutic trial). RESULTS: Of 283 eligible infants,
      161 were screened (participation rate, 57%). Mean (SD) microhematocrit by skin
      puncture was 35.9(2.2)%. Thirteen infants (8%, 95% Cl: 4 to 13%) were anemic, and
      7 infants (4%, 95% Cl: 2 to 9%) demonstrated iron deficiency anemia in the
      therapeutic trial. There was no significant difference between study sites in
      mean microhematocrit, and prevalence of anemia or iron deficiency anemia.
      CONCLUSIONS: The prevalence of anemia and iron deficiency anemia among infants in
      the study communities is high enough to warrant considering routine screening.
      Further studies are needed to determine whether a high prevalence of anemia is
      widespread in Japan.

PMID- 12043181
TI  - [A study of relation between disease and nutrition in Shiga prefecture].

PMID- 12043182
TI  - [Reference birthweight for multiple births in Japan].
AB  - PURPOSE: Intrauterine growth curves of twins, that is, birth weights according to
      gestational age, were calculated from birth certificate data. METHODS: Multiple
      births were identified by birthplace, ages of the parents, gestational age, and
      year and month of birth. There were 49,240 twin births in Japan between 1988 and
      1991. Of these, 32,232 livebirth-livebirth pairs, 679 livebirth-stillbirth pairs,
      and 278 stillbirth-livebirth pairs were included in this analysis. There were
      also 1894 triplet live births from 744 sets of triplets and 206 quadruplet live
      births analyzed. For all, access was made to the database of birth certificates
      in the form of magnetic tapes giving birthweights in hundred gram categories.
      RESULTS: For all gestational ages, median birthweights of males were ca. 0.05 kg
      0.1 kg larger than female values. Compared to singleton births in Japan, median
      birthweights of twins remained ca. 0.15 kg smaller until gestational age of 34
      weeks, the difference then increasing to ca. 0.5 kg at 42 weeks of gestation. As
      for birth order, mean birthweight of the first twin was larger than that of the
      second and the standard deviation was larger for the second. Birthweights of
      twins from multiparous mothers were greater than those from primiparous mothers.
      Among the multiple births, median birthweight for gestational age was found to be
      greatest in twins, lower in triplets and lowest in quadruplets. In triplets, the
      50th centile for boys was 0.08 kg larger than for girls. DISCUSSION: With regard
      to perinatal growth, the fetus is affected more or less by the limitation of
      uterine expansion in the late gestational weeks. Reference birthweights for
      exclusive use for multiple births are different from that for singletons.

PMID- 12043183
TI  - [The present status and future of organ transplantation].

PMID- 12043184
TI  - [Biclonal light chain gammopathy in multiple myeloma--a case report].
AB  - A 74-year-old woman was admitted to our hospital in March 1998 for low-back pain.
      In 1990, she had a chemotherapy for diffuse mixed cell lymphoma. Biochemical and
      serologic assays revealed a total protein level of 9.7 g/dl and an IgG level of
      4,530 mg/dl. Immunoelectrophoresis showed monoclonal IgG protein associated with
      two monoclonal kappa and lambda light chain components. Bone marrow examination
      showed proliferation of myeloma cells comprising up to 25% of all nucleated
      cells. Myeloma cells were immunohistochemically positive for IgG and kappa and
      lambda light chains. IgG contained equal amounts of IgG 1 and IgG 2 subtypes and
      the complementarity determining region 3 (CDR 3) of myeloma cells showed
      oligoclonality by polymerase chain reaction, suggesting the myeloma cells may
      have two components. The patient received melphalan and prednisone in
      combination, resulting in only a minor response. She eventually developed
      angioimmunoblastic T-cell lymphoma. Biclonal gammopathy associated with malignant
      lymphoma is rare in case of multiple myeloma and may provide some insight into
      the pathogenesis of plasma cell tumors.

PMID- 12043185
TI  - [A case of idiopathic fibrosing mediastinitis presented with bilateral pleural
      effusion].
AB  - A case is reported of a 56-year-old male who presented with bilateral pleural
      effusion as an initial manifestation of idiopathic fibrosing mediastinitis. The
      patient showed shortness of breath with severe loss of vital capacity and weight
      loss. A mediastinal mass surrounding the thoracic aorta and bilateral pleuritis
      was identified by the chest CT scan. The mass extended, along the abdominal
      aorta, to the upper portion of retroperitoneum. Laboratory data showed elevated
      levels of C-reactive protein (CRP), erythrocyte sedimentation ratio (ESR), and
      IgG. Biopsy of the mediastinal and the pleural mass showed adipose tissue and
      fibrosis with mild perivascular inflammatory infiltration. A diagnosis of
      idiopathic fibrosing mediastinitis was made, and 40 mg/day of prednisolone was
      administered. Although CRP and ESR was normalized, the mass size and vital
      capacity were almost unchanged.

PMID- 12043186
TI  - [A case of classical polyarteritis nodosa diagnosed by myocardial biopsy].
AB  - We experienced a girl with polyarteritis nodosa (PN) diagnosed by myocardial
      biopsy. The symptoms began with high fever and skin rash. These symptoms and
      laboratory findings temporarily improved by oral prednisolone, however, she
      flared up with chest pain about 40 days after onset of the disease.
      Electrocardiogram indicated the elevation of ST-T levels and low voltage, and
      blood examination showed remarkable elevation of creatine phosphokinase (CK),
      white blood cell count (WBC), aspartate aminotransferase (AST) and lactic
      dehydrogenase (LDH) levels. We suspected systemic vasculitis and damage of
      coronary artery or/and heart muscle. Finally, she was diagnosed with classical
      polyarteritis nodosa by myocardial biopsy. Coronary angiography revealed no
      abnormalities. The combination therapy of cyclophosphamide pulses and plasma
      exchange was very effective to suppress the disease activity.

PMID- 12043187
TI  - [Report of a patient of primary Sjogren syndrome, IgA nephropathy and chronic
      idiopathic thrombocytopenic purpura].
AB  - We describe the case of a 61-year-old woman diagnosed with primary Sjogren's
      syndrome (SS) after an 8-year history of IgA nephropathy and a 3-year history of
      recurrent purpuric rashes. Her two daughters had previously been diagnosed with
      other autoimmune diseases. One daughter had Graves' disease and the other had
      Hashimoto's disease and systemic lupus erythematosus. The diagnosis of SS was
      made based on dryness of mucous membranes, Shirmer test, and parotid sialography.
      Thrombocytopenia, high platelet-aggregated IgG (PA-IgG) level, and normal
      megakaryocytes count in bone marrow suggested that her recurrent purpuric rashes
      were due to idiopathic thrombocytopenic purpura (ITP). Patients with SS may
      develop other autoimmune diseases. This case aids understanding of the immune
      pathogenesis and genetic background of SS.

PMID- 12043188
TI  - [A case report of lymphomatoid granulomatosis (LYG) with spontaneous
      attenuation].
AB  - 70 years old woman was admitted to our hospital for the evaluation of multiple
      nodular shadows on chest X-ray. She had no clinical symptoms despite of mild
      increase of LDH and decrease of PaO2 on laboratory examination. Video associated
      thoracic surgery was performed to obtain lung tissue for the pathological
      diagnosis. Pathological findings suggested a diagnosis of lymphomatoid
      granulomatosis (LYG) for her lung nodules, which was confirmed by rearrangement
      of IgJH with nested PCR of lung tissue. Nodular shadows in her lung had a trend
      to regress in accordance with decreases of makers for lymphoma such as sIL-2 R,
      thymidine kinase, and beta 2-microglobulin without any medication. This is a rare
      case report of LYG with spontaneous attenuation in the clinical course.

PMID- 12043189
TI  - [Two cases of limited cutaneous nodular amyloidosis with primary Sjogren's
      syndrome].
AB  - We described two female patients with primary Sjogren's syndrome associated with
      localized cutaneous nodular amyloidosis (LCNA), in which amyloid protein was
      derived from immunoglobulin light chain. Case 1; a 70-year-old female had
      complained with polyarthralgia, low-grade fever and parotid gland swelling. She
      was diagnosed as primary Sjogren's syndrome. Three years later she noticed brown
      color small tumor on the thigh and yellow to brown nodules on the bilateral
      calves of legs. Skin biopsy from the left thigh revealed amyloid L protein
      deposition, which was positive for anti-lambda light chain staining, in almost
      entire dermis. Infiltration of lymphocytes and plasma cells around the amyloid
      deposit were prominent. Case 2; a 51-year-old female had noticed increasing
      eruption on the hip. Skin biopsy revealed amyloid L protein deposition in the
      dermis, which was negative for anti-lambda nor kappa light chain staining. When
      she was refereed to our hospital, she complained of xerostomia and xerophthalmia.
      She was diagnosed as primary Sjogren's syndrome. In both cases, histological
      examination of a minor salivary gland biopsy revealed infiltration of lymphocytes
      and plasma cells but not amyloid deposit. Serum M protein and urine Bence-Jones
      protein were not detected. These cases represent localized amyloidosis without
      systemic involvement. It is widely recognized that Sjogren's syndrome is
      frequently accompanied by B cell lymphoproliferative disorders. In LCNA,
      infiltration of plasma cells around the amyloid deposits was frequently
      prominent. The relation between these two disorders is discussed.

PMID- 12043190
TI  - [Mixed connective tissue disease].

PMID- 12043191
TI  - [Epidemiological study on tobacco smoking and dependence in Hokkaido Prefecture].
AB  - A 1998 national survey of smoking and health problems reported that 18 million
      Japanese over 15-years-old, 53.9% of regular smokers in Japan, have tobacco
      dependence. The survey used the Tobacco Dependence Screening Questionnaire (TDS),
      the items in which do not strictly follow the criteria for ICD-10 dependence
      syndrome. In this study, to evaluate the validity of screening with the TDS for
      ICD-10 tobacco dependence, TDS and a questionnaire, consisting of items obtained
      from the ICD-10 dependence syndrome for tobacco use were administered to 1371
      participants. The prevalence of tobacco dependence diagnosed according to the ICD
      10 criteria was 20.9%. On the other hand, the ratio of tobacco dependence
      screened by the TDS was 60.1%. Furthermore, only 26.0% of participants screened
      as tobacco dependent by the TDS were diagnosed as being tobacco dependence
      according to ICD-10 criteria. These results indicate the possibility of
      overestimation of the rate of tobacco dependence using the TDS.

PMID- 12043193
TI  - [Alcohol action and activation of NF-kappa B].
AB  - Alcohol consumption causes expression of numerous genes. The transcription
      factor, nuclear factor-kappa B (NF-kappa B), is found in essentially all types of
      cells and is involved in activation of an exceptionally large number of genes in
      response to infections, inflammation, and other stressful situations requiring
      rapid reprogramming of gene expression. Therefore, gene expression caused by
      alcohol consumption could be regulated via active NF-kappa B. This review focuses
      on the NF-kappa B signaling pathway under alcohol consumption, especially by
      acute alcohol loading.

PMID- 12043192
TI  - Changes of bcl-2 and bax mRNA expressions in the ethanol-treated mouse brain.
AB  - To characterize the biochemical mechanism of cell death induced by ethanol
      intoxication, we examined expression of mRNAs of bcl-2 and bax genes in the
      brain, which are related to apoptosis, by using the reverse transcription
      polymerase chain reaction method (RT-PCR). According to ethanol administrations,
      the expression of bcl-2 mRNA in the cerebral cortex decreased after 1 day and be
      recovered after 3 days. The expression of bcl-2 mRNA in the cerebellum was not
      changed soon after 1 day and increased after 3 days. The expression of bax mRNA
      in the cerebral cortex decreased after 1 day and be recovered after 3 days. The
      expression of bax mRNA in the cerebellum increased after 1 day and after 3 days.
      We found that bcl-2 or bax mRNA expressions in the brain were changed after short
      term ethanol exposure. These results suggest that bcl-2 or bax may have
      functional significance about ethanol intoxication.

PMID- 12043195
TI  - [Strategies for treatment of childhood leukemia].

PMID- 12043194
TI  - [Paroxysmal nocturnal hemoglobinuria (PNH) as a hematopoietic stem cell disorder-
      long-term support of hematopoiesis by a single stem cell clone in patients with
      PNH].

PMID- 12043196
TI  - [Novel molecular therapy for acute promyelocytic leukemia (APL): application of
      the green tea component, catechin].

PMID- 12043197
TI  - [Histone deacetylase-targeted anti-leukemia therapy].

PMID- 12043198
TI  - [Results of clinical studies on a selective inhibitor of ABL tyrosine kinase
      (STI571) in patients with Ph(+) leukemia].

PMID- 12043199
TI  - [Inhibition of leukemogenic signaling and its therapeutic implications].

PMID- 12043200
TI  - [Two-color FISH analysis of clonal evolution in aplastic anemia].

PMID- 12043201
TI  - [Pathophysiology of monopathic myelodysplastic syndrome, especially with
      thrombocytopenia].

PMID- 12043202
TI  - [Pathological analysis of myelodysplastic syndrome with myelofibrosis].

PMID- 12043203
TI  - [Mutation of GSTT-1 gene in MDS patients and its clinical application].

PMID- 12043204
TI  - [Treatment of myelodysplastic syndromes with immunosuppressive agents].

PMID- 12043205
TI  - [Relationship between response to cyclosporine treatment and HLA-DR in MDS].

PMID- 12043206
TI  - [Self-renewal potential of hematopoietic stem cells].

PMID- 12043207
TI  - [The process of lineage commitment in hematopoiesis].

PMID- 12043208
TI  - [Signal transduction in hematopoiesis: a functional role of Stat 1 and Stat 3 in
      erythropoiesis and megakaryopoiesis].

PMID- 12043209
TI  - [A role of chemokine SDF-1/PBSF in hematopoiesis].

PMID- 12043210
TI  - [Ex vivo expansion of human hematopoietic stem cells and their ability to
      differentiate into functional immune-competent cells].

PMID- 12043211
TI  - [Primary pancreatic lymphoma with elevated serum CA19-9 level].
AB  - We report a case of primary pancreatic lymphoma. The patient was a 71-year-old
      Japanese male who complained of upper abdominal pain. The findings on imaging
      examinations including CT scan, angiograph, and ERCP suggested pancreatic head
      adenocarcinoma. CA 19-9 levels were elevated. The patient underwent
      choledochojejunostomy and gastrojejunostomy. Histologically, swollen mesenteric
      lymphnodes biopsied intraoperatively showed lymphoplasmacytic lymphoma findings.
      Leakage occurred repeatedly postoperatively, and the patient died of sepsis.
      Retrospectively, relatively clearly defined and homogenous low density mass
      lesion seen on CT scan were more likely findings for lymphoma than for
      adenocarcinoma. It is important to consider lymphoma in a patient with suspected
      adenocarcinoma showing atypical imaging findings no matter how minor they are.

PMID- 12043212
TI  - [Successful treatment of Crow-Fukase syndrome with radiation therapy].
AB  - A 73-year-old woman was referred to our hospital because of gait disturbance. She
      had peripheral polyneuropathy which was mainly of the demyelinating type,
      splenomegaly, a skin change and M protein (IgA-lambda). A bone scinti and a CT
      scan showed a mass lesion in the thoracic vertebra, and a biopsy revealed
      plasmacytoma. She was diagnosed as Crow-Fukase syndrome, and treated with local
      radiation therapy. After the treatment, M protein became undetectable, and gait
      disturbance was improved.

PMID- 12043213
TI  - [Current status of radiation therapy--evidence-based medicine(EBM) of radiation
      therapy. Metastatic brain tumors].
AB  - The prognosis of patients with brain metastases is poor. Consequently, the
      purposes of treatment for such patients are also limited. One goal is to prevent
      the metastatic tumors from causing death, and another is to improve the
      neurological symptoms that are causing deterioration of the patient's quality of
      life. There are several treatment options for brain metastases: whole brain
      irradiation, surgery, stereotactic radiosurgery, and combinations of these. We
      reviewed recent reports that were based on the evidence obtained from various
      treatment strategies for this condition. We concluded that the final decision
      should be made by the patients themselves. We refer to the concept of narrative
      based medicine(NBM).

PMID- 12043214
TI  - [Current status of radiation therapy--evidence-based medicine (EBM) of radiation
      therapy. Radiotherapy for pharyngeal and laryngeal cancer].
AB  - Radiation therapy is the first choice of treatment for early pharyngeal and
      laryngeal cancers, especially those of the glottic larynx and nasopharynx. For
      advanced lesions without distant metastasis, more intensive treatments, i.e.,
      chemoradiotherapy, multiple fractions per day, and conformal radiotherapy are
      introduced to improve local control and survival. However, the level of evidence
      based medicine is different for each treatment modality. In this review, recent
      reports of radiotherapy for pharyngeal and laryngeal cancer are introduced from
      the point of view of the evidence level.

PMID- 12043215
TI  - [Current status of radiation therapy--evidence-based medicine (EBM) of radiation
      therapy. Current management of patients with esophageal cancer].
AB  - The best management for small mucosal esophageal cancer is generally endoscopic
      mucosal resection. However, for submucosal cancer and extensive mucosal cancer,
      either radical surgery or radiation seems to be an equally efficacious option.
      Radiation therapy concurrent with chemotherapy is more effective than radiation
      therapy alone for patients with unresectable esophageal cancer. The key drugs are
      cisplatin and 5-fluorouracil. However, for patients with poor performance status
      or for aged patients, radiation therapy alone is still a choice of treatment.
      Surgery has generally been indicated for patients with resectable esophageal
      cancer. However, outcomes of concurrent chemoradiation therapy may be comparable
      with those of surgery. Therefore, a prospective randomized study should be
      performed to determine the best management for patients with resectable
      esophageal cancer. The usefulness of intra-cavitary irradiation for esophageal
      cancer has not been clarified. A prospective randomized trial with a large number
      of patients is necessary to determine the effectiveness of intra-cavitary
      irradiation. The best management for patients with loco-regionally recurrent
      esophageal cancer after surgery has not been determined. Intensive therapy should
      be considered if the site of recurrence is limited and the time interval from
      surgery to recurrence is long. Chemotherapy is essential in the management of
      patients with small cell esophageal cancer. However, the best local therapy has
      not been determined.

PMID- 12043216
TI  - [Current status of radiation therapy--evidence-based medicine (EBM) of radiation
      therapy. Breast cancer].
AB  - Evidenced-based medicine(EBM) is undergoing rapid acceptance as a principle of
      decision making in radiation oncology clinics. Adjuvant therapy for breast cancer
      is one of the most actively researched areas, and there is a great deal of
      clinical evidence of high-quality treatment of breast cancer. The case of 47-year
      old premenopausal woman who underwent consultation for postmastectomy
      radiotherapy (PMRT) is presented, and the course of practice using EBM is
      described. Because she had one positive axillary lymph node, she received
      systemic chemotherapy with doxorubicin, cyclophosphamide, and paclitaxel. She is
      also receiving trastuzumab and tamoxifen. She underwent immediate reconstruction
      with a TRAM flap. Existing guidelines point out that PMRT significantly reduces
      the risk of local recurrence; however, none of them recommend PMRT for a patient
      with < 4 positive lymph nodes because of the lack of firm evidence for
      improvement of overall survival. There is also some evidence that PMRT after
      immediate reconstruction reduces the cosmetic result and that paclitaxel might
      increase the risk of radiation pneumonitis even in sequential administration. She
      chose PMRT, although our recommendation was not to do so. Expertise in the area
      of breast cancer as well as high-level evidence developed in Japan is essential
      to effectively implement EBM.

PMID- 12043217
TI  - [Efficacy and safety of polaprezinc as a preventive drug for radiation-induced
      stomatitis].
AB  - BACKGROUND: Radiation-induced stomatitis is one of the adverse effects of total
      body irradiation(TBI). We examined the usefulness of oral polaprezinc as a
      preventive drug for stomatitis. PATIENTS AND METHODS: The present study was
      conducted with 19 patients who were diagnosed with hematologic malignancy and who
      underwent TBI as pretreatment for bone marrow transplantation, peripheral blood
      stem transplantation, or cord blood stem cell transplantation. Eleven patients
      ingested the suspension of polaprezinc and 2% carmellose sodium
      (carboxymethylcellulose sodium: CMC) beginning the day before TBI(P-CMC group),
      while the other eight patients did not ingest P-CMC(control group). The severity
      of stomatitis was assessed in each group during a four-weeks period. RESULTS:
      Stomatitis (Grade: > or = 3) developed in one of 11 patients in the polaprezinc
      group and in 4 of 8 patients in the control group(P = 0.046). The times at which
      stomatitis development ranged between weeks 1 and 2 after the onset of TBI in the
      two groups. No adverse reaction owing to the ingestion of P-CMC was observed.
      CONCLUSIONS: These results suggested the efficacy and safety of polaprezinc as a
      preventive drug for radiation-induced stomatitis.

PMID- 12043218
TI  - [Laser-radiation therapy for T2N0M0 laryngeal-glottic cancer].
AB  - PURPOSE: To evaluate the laser-radiation combined therapy for T2N0M0 laryngeal
      glottic cancer in order to preserve the larynx. METHODS AND MATERIALS: The
      subjects consisted of 52 patients with T2N0M0 laryngeal-glottic cancer treated
      with laser-radiation combined therapy between 1980 and 1999. Patients ranged in
      age from 40-88 years, with a median of 70 years, and included 51 men and one
      woman. During this period, treatment was administered with different radiation
      devices(60Co or 4 MV-X ray), and 40-72 Gy (median, 60 Gy) of radiation therapy
      ware administered. Tumor and treatment characteristics were correlated with local
      control at a median follow-up of 61 months(range 12-210 months). Concurrent
      chemotherapy was administered to 32 patient; 29 were treated with 5-FU and
      vitamin A(FAR), and 3 were treated with low-dose CDDP. Post treatment vocal
      function was examined in 37 patients. The voice was evaluated in terms of four
      parameters: maximum phonation time (MPT), mean air flow rate during phonation
      over a comfortable duration(MFR), fundamental frequency range of phonation(F0
      range), and sound pressure level range of phonation (SPL range). RESULTS: The
      five-year cause-specific-survival rate was 98.0%, and the local control rate was
      91.8%. Three of 4 patients who had locally relapsed were administered total
      laryngectomy as salvage therapy. One patient was administered the tracheostomy
      for late complication. The actuarial laryngeal preservation rate was 92.3%. We
      did not find any significant relationship between local relapse and extent of
      disease, subglottic extension, or anterior commissure involvement. Concurrent
      chemotherapy was not a significant prognostic factor. Laser debulking followed by
      radiation therapy did not change the voice significantly except the F0 range.
      CONCLUSION: We conclude that the laser-radiation combined therapy for T2N0M0
      laryngeal-glottic cancer was effective therapy for not only preservation of the
      voice but also for vocal function.

PMID- 12043219
TI  - [Development of stereotactic irradiation system of body tumors under respiratory
      gating].
AB  - Stereotactic radiosurgery for body tumors is hampered by the difficulties in body
      fixation and respiratory motions of the tumor. We have developed a Microton-based
      system for the stereotactic irradiation of body tumors, which delivers radiation
      at a predetermined respiratory phase. The patients are fixed non-invasively in
      the custom-made bed, and CT images are obtained. The isocentor is calculated with
      reference to those images and is marked onto the patient's skin and the custom
      made bed. The patient lying on the bed is transferred to the treatment couch of
      the Microtoron. After reproducing the isocenter, actual treatment is started. The
      treatment couch as well as the gantry move automatically around the isocenter
      according to the treatment planning. The circular collimator moves by computer
      control to reduce geometrical errors to less than 0.5 mm, which is evoked by
      gantry movement. Respiratory movement of the abdominal wall is measured by laser
      displacement monitor. The Microtron delivers X-rays at a predetermined
      respiratory phase with a lag time of 20 msec after the on-signal from the
      monitor.

PMID- 12043220
TI  - [Expression of stress protein (HSP 70) in adrenalectomized mice].
AB  - We have already reported that the expression of HSP 70 in the adrenal gland was
      the most apparent among all organs in whole body-heated mice. In this paper, we
      examined the relation between the induction of HSP 70 and the adrenal gland using
      adrenalectomized mice. The expression of HSP 70 in some organs of
      adrenalectomized mice was significantly lowered in comparison with control mice.
      Adrenalectomy attenuated whole body heating-induced HSP 70 induction in some
      organs. Low expression of HSP 70 in adrenalectomized mice was a result to high
      mortality caused by endotoxin shock. These results indicate that the adrenal
      gland plays an important role in the response to stress, leading to the induction
      of HSP 70.

PMID- 12043221
TI  - [Non-small cell lung cancer (NSCLC)].
AB  - The goal of radiation therapy for non-small cell lung cancer (NSCLC) is to
      improve the survival rate of patients without increasing treatment-related
      toxicity and to improve patients' quality of life. Several prospective randomized
      trials have demonstrated a survival advantage in combined modality treatment over
      radiotherapy or chemotherapy alone when a cisplatin-based chemotherapy regimen is
      utilized in the treatment plan. Combined modality treatment of cisplatin-based
      chemotherapy and radiotherapy is standard treatment for selected patients such as
      those with better performance status with locally or regionally advanced lung
      cancer including T3-T4 or N2-N3. Determining the contribution of new agents in
      combined modality treatment will require carefully designed and conducted
      clinical trials. High-dose involved field radiation therapy using 3D-conformal
      radiation therapy potentially enables the use of higher doses than standard
      radiation therapy, because less normal tissue is irradiated, and may improve
      local control and survival. The combination of radiotherapy with chemotherapy and
      dose escalation using 3D-conformal radiation therapy is also a possibility in
      unresectable NSCLC. In surgery cases, the results of several Phase III trials of
      cisplatin-based preoperative chemotherapy have suggested survival improvement.
      But the concept needs to be tested in a larger Phase III trial.

PMID- 12043222
TI  - [Limited stage small cell lung cancer].
AB  - Recent progress in the treatment of limited stage small cell lung cancer (LD
      SCLC) is reviewed. SCLC represents 15-20% of all lung cancers. Combination
      chemotherapy is considered the treatment of choice because SCLC usually is
      widespread at diagnosis. The PE (CDDP + Etoposide) regimen and concurrent
      thoracic irradiation have yielded the best survival results in LD-SCLC. Although
      the timing of chemotherapy and thoracic radiation is still controversial, the
      early integration of chemotherapy and thoracic irradiation produces a small
      survival advantage over the late integration of chemoradiotherapy. Radiotherapy
      should be delivered to a smaller target volume based on CT planning, and twice
      daily chest irradiation (accelerated hyperfractionation) is recommended because
      of improvement in local control and survival. Meta-analysis has shown that
      prophylactic cranial irradiation reduced the rate of brain metastases and
      increased 3-year survival by 5% in patients with SCLC in complete response.

PMID- 12043223
TI  - [Uterine cervical cancer].
AB  - Most practice standards have been determined empirically in radiotherapy for
      uterine cervical cancer. On the other hand, a large volume of clinical data on
      cervical cancer has been published. A practice of evidence-based medicine (EBM)
      can offer the most suitable management for individual patients with cervical
      cancer.

PMID- 12043224
TI  - [Prostate cancer].
AB  - The incidence of prostate cancer has been increasing gradually in Japan, and the
      optimal use of radiation therapy is important to improve therapeutic outcome and
      quality of life. The clinical trials conducted by RTOG and EORTC have made it
      clear that dose escalation results in improvement of the local control rate in
      early stage localized prostate cancer and androgen ablation in combination with
      radiation therapy improves biochemical control and the progression-free survival
      rate in locoregionally advanced prostate cancer. To select optimal patients for
      dose escalation study and to determine the optimal use of androgen ablation, it
      has become clear that the Gleason score and pretreatment PSA value provide
      valuable information in addition to clinical stage. In terms of prophylactic
      irradiation to pelvic lymph nodes, there has been no definitive evidence that
      prophylactic irradiation of clinically or pathologically uninvolved pelvic lymph
      nodes improves the overall survival rate. Brachytherapy including 125-I or 103-Pd
      permanent implants and high-dose-rate brachytherapy is now widely used in the
      treatment of prostate cancer, but clear indications have not yet been determined
      because of the lack of clinical trials. In this paper, we summarize evidence
      concerning the role of radiation therapy in the treatment of prostate cancer and
      also describe the biological basis of prostate cancer, which influences the
      optimal selection of treatment modalities.

PMID- 12043225
TI  - [Non-Hodgkin's lymphoma].
AB  - Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lympho-proliferative
      disorders, mainly originating in lymphoid tissues and other extranodal organs,
      with different patterns of behavior. Prognosis depends on the histo-pathologic
      type, prognostic factors, and treatment. According to the WHO classification
      (2001), the NHLs are divided into two prognostic groups: the indolent lymphomas
      (follicular lymphoma, marginal zone B-cell lymphoma, etc.) and the aggressive
      lymphomas (diffuse large B-cell lymphoma, peripheral T-cell lymphoma, etc.).
      Indolent NHLs have a good prognosis, with median survival as long as 10 years,
      and early stage (I and II) indolent NHLs can be treated with radiation therapy
      alone, with 70% to 90% 5-year overall survival rates. The aggressive NHLs have
      shorter natural histories, but the number of patients cured with intensive
      chemotherapy currently is increasing. In general, overall survival at 5 years is
      approximately 50% to 60%. Patients with stage I and contiguous stage II
      aggressive NHLs enjoy excellent survival rates when treated with a combined
      modality including chemotherapy (CHOP) and radiation therapy. The radiation dose
      for NHLs varies from 25 to 50 Gy and is dependent on pathologic type and the
      organs at risk. Radiation fields are basically limited to involved regions or
      extended to immediately adjacent sites. Localized presentations of extranodal
      NHLs can be treated with involved-field techniques with significant success.
      However, the long-term adverse reactions must be considered carefully.

PMID- 12043226
TI  - [Hodgkin lymphoma].
AB  - In the newly published WHO classification for tumors of the hematopoietic and
      lymphoid tissues, Hodgkin's disease has been renamed Hodgkin lymphoma, which
      reflects the recent confirmation of its germinal center B-cell origin. In the
      classification, nodular lymphocyte-predominant Hodgkin lymphoma has been added as
      a new entity with an excellent prognosis. For management of the disease, a risk
      adapted classification is employed without staging laparotomy. In limited stages
      without risk factors, subtotal nodal irradiation with sophisticated techniques
      can cure more than 80% of patients. Multimodality therapy with chemo- plus
      radiotherapy can improve disease-free survival, but overall survival remains
      unchanged. In the intermediate stages with risk factors, chemo- plus radiotherapy
      is standard, with 3-4 cycles of ABVD and involved field irradiation. In advanced
      stages, chemotherapy plays a decisive role, with radiation therapy used as an
      adjuvant for bulky and/or slowly responding tumors. Long-term follow-up of cured
      Hodgkin patients has revealed increased incidences of solid malignancies and
      ischemic heart disease more than 15 years after therapy. Breast cancer and
      ischemic heart disease appear to be related to mantle irradiation, although
      sophisticated modern radiation therapy techniques are demonstrated to lower the
      incidence of these long-term morbidities. Meticulous radiation therapy remains
      the most effective tool for local control of Hodgkin lymphoma.

PMID- 12043227
TI  - [Line scan diffusion weighted imaging (LSDI) on 0.2 Tesla MRI of the normal
      cervical cord in vivo: preliminary study].
AB  - Diffusion weighted imaging(DWI) has been widely performed in the brain. However,
      DWI of the spinal cord is rarely performed because of technical and physiologic
      problems. Line scan diffusion weighted imaging(LSDI) is spin-echo based and
      relatively insensitive to susceptibility artifacts. We calculated the apparent
      diffusion coefficient(ADC) values of the normal cervical spinal cord by LSDI on a
      0.2 Tesla MR imager and compared the ADC values with those from 1.5 Tesla MRI
      previously reported in the literature. The ADC values were adequate, and LSDI on
      0.2 Tesla MRI is expected to become a useful tool for clinical application.

PMID- 12043228
TI  - [Catheter placement in the right gastroepiploic artery without fixation using a W
      spiral catheter for implantable reservoir therapy of malignant liver tumors].
AB  - Intra-arterial infusion chemotherapy using a percutaneously implanted port
      catheter system was performed in 21 patients with liver tumors. We developed a
      new procedure, the gastroepiploic method, using a W Spiral Catheter without
      embolization around/within the catheter and embolization for the right
      gastroepiploic artery distal to the catheter tip. After embolizing the
      gastroduodenal arterial branches, right gastric artery, or aberrant hepatic
      arteries, we mainly inserted the catheter tip into the right gastroepiploic
      artery. There were no complications such as peptic ulcer, hepatic artery
      obstruction, or catheter dislocation (observation time, 5.3 months). This method
      seemed to be feasible for implantable reservoir therapy of patients with
      malignant liver tumors.

PMID- 12043229
TI  - [A case of adenomyosis showing multiple large cysts on MR imaging].
AB  - Adenomyosis is a condition characterized by benign invasion of the endometrium
      into the myometrium associated with reactive hypertrophy of the surrounding
      musculature. The ectopic endometrium in adenomyosis is of the basalis type, and
      menstrual bleeding is less common than in endometriosis. We report a rare case of
      adenomyosis that had multiple, large, adenomyotic cysts. These cysts were located
      in the outer layer of adenomyosis on MR imaging. Pathologic features consisted of
      blood-filled cysts of 1 cm to 5 cm in maximum diameter of the functioning
      endometrial type.

PMID- 12043230
TI  - [Serum level of secretory phospholipase A2 (sPLA2) as a predictor of restenosis
      after coronary angioplasty].
AB  - AIM: To elucidate whether secretory phospholipase A2 (sPLA2) level in the blood
      and catalytic activity are significant predictors of restenosis after coronary
      angioplasty (CAP). MATERIAL AND METHODS: Samples of venous blood were obtained
      from 24 patients before CAP and 1, 3, 6 days and 6 months after it. sPLA2 was
      measured with enzyme immunoassay, catalytic activity--using aqueous emulsion of
      14C-labelled phosphatidylcholine. Control coronarography was performed in all the
      examinees 6 months after CAP. RESULTS: Restenosis was detected in 13 patients. In
      the serum of their blood sPLA2 rose significantly after CAP and persisted for 6
      days after it. If restenosis was not registered, this rise was insignificant and
      disappeared by day 6 after CAP. Catalytic activity of sPLA2 on day 6 after CAP
      was significantly higher in patients who later developed restenosis. CONCLUSION:
      Elevated concentrations of sPLA2 in blood serum of patients after CAP may predict
      restenosis. Moreover, sPLA2 may not only mark inflammation but directly
      participate in development of restenosis.

PMID- 12043231
TI  - [Comparison of the results of functional tests used in non-invasive examination
      of endothelial function].
AB  - AIM: To analyze results of two tests used in non-invasive assessment of
      endothelial function: D. Celermajer test (T1) and reactive hyperemia test (T2).
      MATERIAL AND METHODS: Ultrasound investigation (7.5 MHz) was employed to measure
      brachial artery (BA) diameter, blood flow rate and its volume at rest above the
      site of occlusion (T1) and under it (T2). Control group consisted of 30 men with
      risk factors for atherosclerosis. RESULTS: Peak value of the diameter dilation
      was within 10% in both tests, the difference being insignificant. The same
      dilatation of BA can be explained by different shift effect on the endothelium:
      in T1 the shift disturbance was longer while in T2 it was more intensive.
      CONCLUSION: To reveal endothelial dysfunction, the site of occlusion and location
      of the artery are not very important. However, because the shift disturbance time
      is different it is desirable to use the same test modification in one trial
      protocol.

PMID- 12043232
TI  - [Diagnostic significance of antibody detection to various hepatitis C virus
      antigens in patients with acute and chronic HCV-infection].
AB  - AIM: To examine diagnostic value of antibodies to various HCV antigens in
      patients with acute and chronic HCV-infection. MATERIAL AND METHODS: Enzyme
      immunoassay has tested blood sera from 136 patients with icteric acute hepatitis
      C (AHC) and 45 patients with chronic HCV infection for IgG antibodies to antigens
      of proteins core, NS4, NS5, HCV. Synthetic peptides core-16, NS4-20, NS5-23 were
      used as antigens. RESULTS: Patients with icteric AHC had IgG antibodies to
      antigens of both structural protein core and non-structural proteins NS4, NS5 of
      HCV as early as the first 10 days of jaundice. Occurrence of anti-core and anti
      NS4 increases with the disease duration. Incidence of anti-NS4 correlated with
      duration of previous intravenous drug addiction. In patients with AHC early in
      the icteric period anti-core, anti-NS4, anti-NS5 were present less frequently
      than in patients with chronic HCV infection having elevated levels of AlAT.
      Significant differences were found neither with the group with normal AlAt nor in
      the spectrum of the detected antibodies between patients with acute and chronic
      HCV infection. CONCLUSION: Despite different frequency of anti-core, anti-NS4,
      anti-NS5 detection in patients with icteric AHC and patients with chronic HCV
      infection and high AlAT, their high incidence rate in this or that group and
      absence of differences by the spectrum of the studied antibodies do not allow the
      fact of their detection to be a diagnostic marker differentiating acute HCV
      infection with chronic one.

PMID- 12043233
TI  - [Renal carcinoma: active detection in regular check-ups].
AB  - AIM: To improve early diagnosis of renal carcinoma (RC) in the course of check
      ups. MATERIAL AND METHODS: Regular checkups performed in 1980-1999 detected 715
      cases of renal carcinoma. Among the patients were 452 male (60.2%) and 263 female
      (39.8%) patients. Mean age was 66 years. Screening methods for healthy examinees
      and risk group examinees, RC incidence rate, 1 year lethality and survival were
      assessed. RESULTS: Mean RC incidence rate in men was 80.9, in women 34.9 per
      100,000. Early diagnosis of RC stage I and II made up 58.4 in men and 59.4% in
      women. Significantly more patients with RC stage I and II were diagnosed at
      checkup than among those seeking medical advice. 5-year corrected survival in
      males was 80%, 10-year survival--74%, in females--84 and 80%, respectively.
      CONCLUSION: Check-up raised early diagnosis of RC stage I and II up to 82.3%.
      This, in its turn, improved survival of RC patients.

PMID- 12043234
TI  - [Diagnosis of pulmonary lesions in acute respiratory insufficiency in patients
      with depressed hemopoiesis].
AB  - AIM: To analyse causes of acute respiratory failure (ARF) and methods of
      diagnosis of pulmonary lesions in patients with depressed hemopoiesis (DH).
      MATERIAL AND METHODS: 50 patients with DH and ARF were examined according to the
      protocol including x-ray, computed tomography, fibrobronchoscopy with
      bronchoalveolar lavage, cytological, bacteriological, virusological studies of
      the lavage fluid, biopsy of the lung. The algorithm of the protocol is provided.
      RESULTS: Sensitivity of the lavage fluid in diagnosis of fungal, bacterial,
      pneumocystic and cytomegaloviral infections was 84, 78, 93 and 93%, respectively.
      The cytologic examination of the lavage fluid may detect lung infiltration with
      blood tumors. In complicated diagnostic cases lung biopsy verified pulmonary
      lesion but its conduction aggravated the patients' condition. ARF patients with
      DH, bacterial flora, fungi, cytomegalovirus and pneumocystic infection, pulmonary
      tumor involvement, pulmonary lesions in ATRA-syndrome, non-infectious lesions of
      the lungs after bone marrow transplantation were found in 38, 18, 40, 18, 8 and
      4% of cases, respectively. CONCLUSION: DH patients with ARF should be examined by
      the protocol including both non-invasive and invasive diagnostic methods.
      Accurate diagnosis of ARF causes is the basic reserve in the treatment of such
      patients.

PMID- 12043235
TI  - [Various approaches to tuberculosis diagnosis in patients with hemoblastosis].
AB  - AIM: To characterize diagnosis of tuberculosis in hemoblastosis patients.
      MATERIAL AND METHODS: Diagnosis of active tuberculosis in 2.6% from 2123
      hemoblastosis patients admitted to Hematological Research Center in 1990-1999
      shows that such patients can be referred to high risk group in relation to
      tuberculosis infection. Methods and terms of tuberculosis diagnosis in
      hemoblastosis patients are analysed. RESULTS: Bacteriological and histological
      tests were positive in 27.8% examinees with hemoblastosis. In extrapulmonary
      tuberculosis location, histological diagnosis was positive in 60%. Especially
      helpful is a complex of clinical and x-ray examinations in high tuberculosis
      alertness. This allowed to suspect the infection in 51.9% patients (63.9% had
      pulmonary location). A marked positive response to antituberculosis treatment
      proved tuberculosis diagnosis. CONCLUSION: Difficulties of tuberculosis diagnosis
      in hemoblastosis patients are explained by low informative effectiveness of most
      common methods of this infection verification. Therefore, in addition to
      bacteriological and histological examinations, clinical diagnostic techniques
      should be employed keeping alert in relation of tuberculosis in hemoblastosis
      patients who are at risk to catch this infection.

PMID- 12043236
TI  - [Systemic lupus erythematosus and infectious endocarditis: similarities and
      differences].
AB  - AIM: To compare clinical laboratory data in systemic lupus erythematosus (SLE)
      and infectious endocarditis (IE) for analysis of similar and different features.
      MATERIAL AND METHODS: Clinical and laboratory findings were compared for 72 IE
      and 71 SLE patients examined for a decade. RESULTS: SLE and IE have the following
      common features: fever, pleurisy, pericarditis, hemorrhagic vasculitis, articular
      syndrome, renal disorders, anemia, rheumatoid factor (RF), cryoproteins (CP),
      elevated ESR, concentrations of circulating immune complexes (CIC), IgM.
      Characteristic of SLE were skin erythema, alopecia, Raynaud's syndrome,
      cerebrovasculitis, lymphadenopathy, pneumonitis, frequent articular lesions,
      leucopenia, high IgG levels, CP and antibodies to DNA. IE was characterized by
      thromboembolic complications, splenomegaly, pneumonia, high CIC and medium mass
      molecules concentration, high incidence rate of RF, positive hemoculture.
      CONCLUSION: In spite of known differences between IE and SLE, in some cases
      differential diagnosis is not easy to make. This leads to late etiopathogenetic
      therapy.

PMID- 12043237
TI  - [Acute phase proteins and recurrence of angina after effective coronary
      angioplasty].
AB  - AIM: Analysis of relationships between clinical characteristics of the patients,
      high concentration of acute phase proteins--fibrinogen, C-reactive protein (CRP),
      activity of the inhibitor of type 1 plasminogen activator (PAI-1)--and frequency
      of angina recurrence after successful coronary angioplasty (CA). MATERIAL AND
      METHODS: The trial included 53 patients after successful CA for a single
      hemodynamically significant stenosis. Peripheral blood was examined for plasm
      fibrinogen, CRP, activity of PAI-1 one day before and 2 days, 3 and 6 months
      after CA. After 12-month follow-up the patients were divided into two groups:
      angina-free patients (n = 37) and with recurrent angina (n = 16). RESULTS:
      Significant differences between the above groups were in PAI-1 activity 3 and 6
      months after CA, in CRP initially, on day 2, after 6 months after CA (p < 0.05)
      but multifactor analysis has found that only CRP level both initial and on day 2
      after CA is an independent predictor of recurrent angina pectoris after
      successful CA. CONCLUSION: An anginal recurrence after successful CA can be
      predicted by the initial and postoperative day 2 levels of CRP.

PMID- 12043238
TI  - [Increased expression of monocytic cell adhesion molecules and formation of
      monocyte-thrombocyte aggregates in coronary restenosis].
AB  - AIM: To examine expression of superficial antigens by blood monocytes and
      granulocytes as well as the number of leukocyte-platelet complexes forming in in
      vitro activation in patients subjected to coronary angioplasty; to analyse
      changes in these parameters in coronary restenosis. MATERIAL AND METHODS:
      Membrane expression of leukocytic antigens and the number of leukocyte-platelet
      complexes after activation in the whole blood were measured by direct
      immunofluorescence and flow cytometry in 24 patients who have undergone stenting
      of coronary arteries. 14 of them had angiographically confirmed restenosis.
      RESULTS: The tests discovered high expression of integrins Mac-1 and VLA-4 by
      monocytes and elevated relative number of monocyte-platelet complexes in patients
      with restenosis vs those free of stenosis (1425 +/- 76 and 1195 +/- 71 r.u. for
      Mac-1, 87 +/- 7 and 65 +/- 6 r.u. for VLA-4, 47 +/- 4 and 29 +/- 3%,
      respectively, for monocyte-platelet complexes; p < 0.05 for all the indices).
      CONCLUSION: Coronary restenosis may result from elevated expression of adhesion
      molecules by monocytes manifest in activation of the cells in vitro.

PMID- 12043239
TI  - [Nocturnal hypoxic episodes and structural changes in left ventricular myocardium
      in patients with mild-to-moderate arterial hypertension].
AB  - AIM: To study correlations between structural changes of the left ventricle (LV)
      in patients with mild and moderate arterial hypertension (AH) and severity of
      hypoxic night episodes. MATERIAL AND METHODS: The examination of 50 patients
      (mean age 52 +/- 1 year) with mild and moderate hypertension included
      echocardiographic measurement of LV myocardial mass, calculation of LV myocardial
      mass index. LV hypertrophy was stated in the index 125 g/m2 for men and 110 g/m2
      for women. 24-h monitoring of arterial pressure (TM-2425) and night monitoring of
      hemoglobin saturation of arterial blood with oxygen (SaO2) using pulsoxymeter
      NONIN 8500M were made. The data processing was performed with the use of original
      program ARM-SaO2. Dissaturation was stated if SaO2 fell by 4% and more compared
      to the previous stable level at initial SaO2 level above 90%. The patients were
      divided into two groups according to the number of dissaturation episodes: group
      1 (more than 20 dissaturation episodes) and group 2 (less than 20 episodes).
      RESULTS: The groups were comparable by gender, duration of hypertension, body
      mass index, systolic and diastolic arterial pressure, heart rate. In group I,
      pulse arterial pressure, systolic arterial pressure load for 14 hours, day and
      night were significantly higher. Patients with dissaturation had a significantly
      higher LV myocardial mass and more frequent LV hypertrophy (128 +/- 6 and 106 +/-
      5 g/m2 and 56 and 20%, respectively). The correlation and multifactor regression
      analysis showed a predictive value not only of the pressor parameters but also of
      indices of night hypoxia in relation to structural changes of LV myocardium.
      CONCLUSION: The presence of significant hypoxic episodes in sleep in AH patients
      indicates risk to develop structural changes of LV myocardium.

PMID- 12043240
TI  - [Diagnosis in the 21st century: clinical aspects and new perspectives].

PMID- 12043241
TI  - [The role of an overall coronary bed affection in heart remodeling in patients
      with stenocardia and arterial hypertension].
AB  - AIM: To study a possible role of coronary circulation condition in remodeling
      heart in ischemic heart disease (IHD) patients with hypertension or without it.
      MATERIAL AND METHODS: The examination (veloergometry, echo-CG and Doppler
      echocardiography, selective coronaroangiography and left ventriculography)
      covered 45 hypertensive men with angina of effort functional class III and 69
      normotensive patients. Mean age of the patients was 51.8 +/- 1.2 years, duration
      of the angina 3 to 10 years. RESULTS: Correlation analysis of the data on
      hypertensive examinees discovered a direct correlation between proportional
      overall lesion of the coronary arteries, myocardial mass index and left
      ventricular (LV) index of systolic sphericity, between the sphericity index and
      myocardial mass index. An inverse correlation--with LV ejection fraction.
      CONCLUSION: In anginal patients, coronary circulation is an independent factor
      influencing LV remodeling. With progression of coronary failure remodeling
      intensifies. In patients with angina arterial hypertension contributes to the
      same degree to an increase in the personage of overall affection of the coronary
      bed, LV systolic sphericity index and index of its myocardial mass, forms an
      integral, global risk of heart remodelling and, later, heart failure.

PMID- 12043242
TI  - [Polymorphism of the ACE gene, structural-functional state of the left ventricle
      in patients with post-infarction cardiac failure and effects of the ACE-inhibitor
      Perindopril].
AB  - AIM: To evaluate relationships between structural-functional state of the left
      ventricle (LV) and genotype of angiotensin converting enzyme (ACE) gene in
      patients with postinfarction chronic cardiac failure (CCF) and effects of ACE
      inhibitor perindopril on hemodynamics depending on ACE gene polymorphism.
      MATERIAL AND METHODS: In 52 patients with CCF (functional class III-IV by NYHA
      criteria) who had survived macrofocal myocardial infarction we studied ACE gene
      using thermostable DNA-polymerase Taq. Isolation of genome DNA from human venous
      blood was made by phenolchloroform extraction with the use of chelate polymer
      Chelex-100. Polymerase chain reaction was conducted on amplificator PHC-2 or
      PolyChain II. LV contractile function was studied on echocardiograph "Toshiba SSH
      160A (Japan). Echocardiography was performed before intake of perindopril, in the
      end of titration phase, on therapy month 6 and 12. RESULTS: Genotype II of ACE
      gene was detected in 11(21.1%) patients, ID genotype--in 20(38.5%), DD genotype-
      in 21(40.4%). Patients with ACE gene genotype II and ID have no differences by
      parameters of central hemodynamics. They were divided into two groups: group 1-
      patients with genotypes II and ID of ACE gene, group 2--patients with genotype
      DD. End diastolic volume (EDV), end systolic volume (ESV), index of LV myocardial
      mass were significantly less in group 1 than in group 2 (by 45.7, 81.6 and 31.2%,
      respectively). In group 1 ejection fraction (EF) and %delta S were higher by 35.3
      and 35.7%, respectively. The hemodynamic effect of perindopril was higher in
      group 2. A month therapy resulted in a 8.7 and 14.8% reduction in group 2 EDV and
      ESV, respectively (p < 0.05). This entailed an increase in EF and %delta S by
      18.3% (p < 0.05) and 19.8% (p < 0.05). Later, perindopril retained influence on
      central hemodynamics. Diastolic function to the end of therapy in both groups
      differed insignificantly. CONCLUSION: In CCF patients functional class III-IV
      with the history of myocardial infarction, structural-functional LV parameters
      depend on genotype of ACE gene. Perindopril is most effective in DD-genotype of
      ACE gene.

PMID- 12043243
TI  - [Ultrasound characteristics of common carotid arteries in Chernobyl clean-up crew
      members long after the accident].
AB  - AIM: Detection of early atherosclerosis and some mechanisms of dyscirculatory
      encephalopathy development late after the Chernobyl accident. MATERIAL AND
      METHODS: 57 men (mean age 45.9 +/- 1.18 years) exposed to ionizing radiation
      after the Chernobyl accident in 1986-1987 (random sample) and 28 healthy men
      (control) entered the trial. Their examination included ECG, echocardiography,
      veloergometry (on demand), 24-h monitoring of arterial pressure and Holter
      monitoring, B-mode ultrasonic scanning in combination with dopplerography and
      color mapping of blood flow (triplex scanning) of the right and left common
      carotid arteries on the unit Vingmed CFM (Diasonic Sonotron, Germany) using 7.5
      MHz sensor. Blood serum was examined for total cholesterol and triglycerides.
      RESULTS: Clinical manifestations of atherosclerosis--ischemic heart disease--were
      detected in 11 examinees (19.3%). Thickening of the complex intima-media which is
      thought an early marker of atherosclerosis was identified in 28 examinees
      (49.1%), stenoses and atherosclerotic plaques--in 17(30%) examinees. Three of
      them had hemodynamically significant stenoses. Increased blood flow in common
      carotid arteries combined with enhanced pump function of the left ventricle.
      CONCLUSION: Atherosclerotic vascular alterations detected in the Chernobyl
      wreckers were encountered 2 times more frequently than clinical symptoms of
      atherosclerosis. One of the mechanisms of dyscirculatory encephalopathy in them
      is high blood volume circulating in common carotid arteries in combination with
      left ventricular pump hyperfunction.

PMID- 12043244
TI  - [Predictive value of insulin-glucose homeostasis markers in patients with
      metabolic syndrome X].
AB  - AIM: To clarify informative value of secretory ability of pancreatic beta-cells
      and correspondence of insulin values to glycemia in the course of standard
      glucose tolerance test (GTT) in detection of insulin-resistance in patients with
      arterial hypertension (AH) to verify metabolic syndrome (MS). MATERIAL AND
      METHODS: Correlation and factor analyses were performed of correlations between
      glycemia, immunoreactive insulin (IRI), C-peptide, glucose/IRI in the course of
      GTT in 111 AH patients divided into groups by the sum of metabolic disturbances.
      RESULTS: The greatest number of correlations were seen for glucose/IRI fasting
      index. According to the factor analysis, changed sensitivity to insulin and
      hyperinsulinemia are the first stage of metabolic disturbances in AH irrespective
      of body mass. In obesity the number of the above correlations is maximal.
      Multivariance analysis has shown significant differences between AH patients and
      healthy subjects irrespective of body mass and glucose tolerance. CONCLUSION:
      Basal index glucose/IRI < 6 relative units is informative in all the studied
      variants of metabolic syndrome as regards insulin resistance.

PMID- 12043245
TI  - [A case of gastric cancer diagnosed on the basis of paraneoplastic syndrome].

PMID- 12043246
TI  - [Subacute thyroiditis as a cause of fever].

PMID- 12043247
TI  - [A clinical case of microscopic polyarteritis].

PMID- 12043248
TI  - [A case of infectious endocarditis of the aortic valve successfully treated with
      surgical operation].

PMID- 12043249
TI  - [Differential diagnosis of syncope and epileptic seizure].

PMID- 12043250
TI  - [Focal lesion in the liver: what can the ultrasound do?].

PMID- 12043251
TI  - [Recognition and treatment of malignant neurocardiogenic syncopes].

PMID- 12043252
TI  - [Diagnostic and prognostic aspects of angina pectoris preceding myocardial
      infarction in long-term follow-up].
AB  - AIM: To trace relations of premyocardial infarction (preMI) angina, myocardial
      reserves and clinical peculiarities within a year of outpatient follow-up.
      MATERIAL AND METHODS: Coronary and myocardial reserves were studied in 320 MI
      survivors using veloergometry, transesophageal pacing (TEP), 24-h ECG monitoring,
      echocardiography. Cardiac output reaction to TEP was assessed. RESULTS: Patients
      with preMI attacks of stable angina had coronary reserve 47.9% less than they had
      before MI while cardiac failure by NYHA criteria aggravated by 33.3%. Myocardial
      ischemia at bicycle exercise in these patients developed much later and its
      threshold rose by 34.2%. The degree of cardiac ejection fall in TEP in patients
      without angina before MI was 2.4 times greater than in patients without history
      of IHD. There were specific features of diastolic relaxation of the myocardium
      and variability of cardiac rhythm in the compared groups though the groups did
      not differ significantly by arrhythmia events and morphological characteristics
      of the scar zone. Survival showed a tendency to lowering of lethal outcome risk
      in the compared groups followed up since the observation month 6 without
      significant differences depending on the presence of preMI angina. CONCLUSION:
      PreMI angina contributes to formation of coronary and myocardial reserves which
      are better to assess at TEP and with analysis of hemodynamic reaction to induced
      rise in heart rate.

PMID- 12043253
TI  - [The role of "respiratory" fluoroquinolones in current antibacterial treatment of
      extrahospital pneumonia].

PMID- 12043254
TI  - [Elasticity characteristics of peripheral arteries in essential hypertension].

PMID- 12043255
TI  - [Research in emergency cardiology achievements and perspectives].
AB  - The analysis of diagnosis and treatment of myocardial infarction (MI) at a
      prehospital stage and in critical care units suggested measures how to improve
      qualification of prehospital and critical care cardiological staff. Realization
      of the measures promoted a reduction of lethality in MI patients.

PMID- 12043256
TI  - [Pathogenesis and treatment of cardiac failure in myocardial infarction].

PMID- 12043257
TI  - [Chronic HBV infection].
AB  - Chronic hepatitis B remains one of the most wide-spread and serious viral
      infections in humans worldwide and may lead to cirrhosis and cancer of the liver.
      Eradication of the virus depends primarily on T-cell immune reaction aimed at
      lysis of the infected hepatosytes and suppression of the virus replication
      without cell death due to secretion of proinflammatory cytokines. Pathogenesis of
      the disease is markedly influenced by viral mutations. Persistent hepatitis B
      virus infection can be controlled in 25-40% patients by alpha-interferon and
      nucleoside lamivudine therapy.

PMID- 12043258
TI  - [New trends in chemotherapy of systemic lupus erythematosus: treatment with
      mycophenolate mofetil].
AB  - The review covers current issues of pharmacotherapy of systemic lupus
      erythematosus (SLE) with a focus on a novel immunodepressant mofetil
      microphenolate (MM) which is not inferior in efficiency to a conventional anti
      SLE drug cyclophosphamide which has a worse tolerance.

PMID- 12043259
TI  - [Diagnostic implications of changed red cell count in low-intensity laser
      radiation of blood in elderly patients with coronary heart disease].
AB  - Intravenous laser therapy in combination with medication was conducted in 41
      elderly patients with coronary heart disease (633 nm, 1 mW, 124 mW/cm2). The
      study of qualitative and quantitative (osmotic resistance) erythrocyte indices of
      blood demonstrated the change of erythrocyte number in circulating blood by the
      third laser procedure. Frequency of these changes correlated with duration of the
      treatment course. Intravenous laser therapy had a wider spectrum of effects on
      erythrocyte number than medication. Changes in erythrocyte number in the
      peripheral blood upon intravenous laser radiation reflects efficiency of
      treatment of coronary heart disease patients.

PMID- 12043260
TI  - [Predictive value of echocardiography in infectious endocarditis].
AB  - 182 patients with infectious endocarditis (IE) were examined for correlations
      between valvular bacterial vegetations and IE activity, course, results of
      bacteriological and morphological findings. 81 of the patients had primary IE, 71
      patients had secondary IE which had developed in uncorrected valvular heart
      disease, in 30 patients secondary IE had developed after surgical correction of
      rheumatic heart disease. It is shown that echocardiographic detection of
      bacterial vegetations does not determine IE severity, course and outcome.

PMID- 12043261
TI  - [Diagnostic and therapeutic problems in adult onset Still's disease (data of a
      long-term follow-up)].
AB  - 15 patients with Still's disease of adults (SDA) were followed up for 17 years
      maximum. The disease showed a principal clinical-laboratory syndrome observed
      both in SDA debut and exacerbations (recurrences). Clinical manifestations of SDA
      do not arise stereotypically causing difficulties in its nosological
      interpretation. SDA course is represented by three variants: monophasic
      (monocyclic), recurrent and chronic persisting with development of destructive
      arthritis. Use of nonsteroid antiinflammatory drugs is analysed, indications to
      administration of glucocorticoids and basic treatment are listed. Reversibility
      of systemic SDA manifestations except the articular one is shown. About half of
      the patients develop chronic destructive arthritis. In active SDA, renal
      amyloidosis and chronic renal failure may develop with lethal outcome.

PMID- 12043262
TI  - [Functional system defining optional level of erythrocytes in the organism].
AB  - The authors propose a functional system defining an optimal level of red cells in
      the body. Reception, reverse afferentation, central and actuating mechanisms of
      the above functional system are considered. Self-regulation of the system in
      hypoxia, erythrogenesis processes are outlined.

PMID- 12043263
TI  - [Clinical variants of joint hypermobility syndrome in respect to age].
AB  - Joint hypermotility syndrome (JHMS) was studied in 304 patients (255 women, 49
      men, age 16-50 years) divided by age into four groups (16-20, 21-30, 31-40, 41
      50). It was found that the incidence rate of such symptoms as polyarthralgia,
      recurrent exudates and incomplete joint dislocations with age lowers while that
      of dorsalgia, oligoarthralgia, soft tissue rheumatic syndromes, fibromyalgia
      rises. A monosymptom variant was characteristic for patients of the age 16-20
      years. It manifested with one of the above symptoms (polyarthralgia, dorsalgia,
      recurrent exudates and incomplete joint dislocations). A syndrome variant,
      manifesting with combination of several clinical symptoms, was typical for
      patients over 30. This reflects systemic involvement of connective-tissue
      structures in the pathological process in JHMS and accumulation of degenerative
      alterations in the locomotor system with age.

PMID- 12043264
TI  - [Unstable angina: state of hemostasis and autonomic nervous system].

PMID- 12043265
TI  - [Neuroendocrine dysfunction in female patients with systemic dysplasia of the
      connective tissue].
AB  - The study covered 119 women with systemic undifferentiated dysplasia of the
      connective tissue (DCT) aged 14-39 years. All the examinees had vegetative
      disorders, 26.1% had a neuroendocrine-metabolic form of hypothalamic syndrome
      (HS), 51.3%--premenopausal syndrome, 65.5%--dysmenorrhea. It was found that women
      with DCT and HS develop symptoms of neuroendocrine disorders at earlier age than
      those with HS but free of DCT. Arterial hypertension was registered in 96.8% of
      patients with DCT and HS, 80.3% of DCT patients with premenopausal syndrome.
      Central hemodynamics was different in DCT patients without neuroendocrine
      disorders and with neuroendocrine dysfunction evidencing the role of the latter
      in development of arterial hypertension in DCT.

PMID- 12043266
TI  - [Clinical response to combined treatment with reaferon and iodantipirin in
      patients with chronic HCV- and HBV-infection].
AB  - The treatment was given to 100 patients with chronic virus hepatitis of moderate
      activity and chronicity stage I. Of them, 50 patients received reaferon (3 IU 3
      times a week) in combination with antiviral and immunomodulating drug
      iodantipirin (100 mg/d) given on the days of reaferon injections for 6 months.
      The other 50 patients received reaferon alone in the same doses and duration of
      the treatment course. Efficiency was assessed by the level of ALT, findings at
      polymerase chain reaction, index of histological activity of hepatic biopsy. The
      combined scheme demonstrated higher efficiency and tolerance.

PMID- 12043267
TI  - [Use of recombinant interleukin-2 in hemorrhagic fever with renal syndrome].
AB  - The study enrolled male patients with fever admitted to Ulyanovsk city hospital
      in November-December 2000 with diagnosis of hemorrhagic fever with renal syndrome
      (HFRS). The diagnosis was confirmed serologically. 10 patients received
      recombinant interleukin 2 (rIL-2) in a dose 250,000 IU/day for 5 days. rIL-2 was
      not given to 10 control patients. Both groups received intravenous prednisolone
      in a dose 90 mg/day. The response was assessed by minimal diuresis, maximal serum
      concentrations of urea and creatinine. No lethal outcomes occurred. Minimal
      diuresis was higher, creatinine and urea levels lower in patients on rIL-2 (647.0
      +/- 268.6 mg/day vs 422.0 +/- 198.2 ml/day, p < 0.05; 221.8 +/- 98.1 mcmol/l vs
      398.9 +/- 234.9 mcmol/l, p < 0.05; 14.9 +/- 5.1 mcmol/l vs 22.0 +/- 9.0 mmol/l, p
      < 0.05). Thus, it is evident that rIL-2 reduces symptoms of acute renal failure
      in HFRS patients. Further investigations of rIL-2 treatment in HFRS are needed.

PMID- 12043268
TI  - [Staphylococcal toxic shock syndrome in young women].
AB  - A literature review is presented on staphylococcal toxic shock syndrome. A case
      of this syndrome in a 39-year-old woman is reported. Clinical, pathology,
      treatment data on this condition are analysed.

PMID- 12043269
TI  - [Deforming hand arthropathy in systemic lupus erythematosus].
AB  - A case of systemic lupus erythematosus with deforming hand arthropathy (DHA) is
      reported in a woman observed for 15 years. DHA was presented with stable ulnar
      deviation, deformation of the fingers. This resulted in functional insufficiency
      of the hand of the third degree.

PMID- 12043270
TI  - [The art of communicating with patients].

PMID- 12043272
TI  - [Clinical forms of pulmonary tuberculosis in adults in the Romanati Plains at the
      change of millennium].
AB  - This modest study is trying to surprise the clinic shades spectrum of the
      pulmonary tuberculosis met at adults in the Romanati Plain zone, which was high
      consumption at the end of the second millennium without avoiding the new tones
      which AIDS and the MDR-TB brought. This things determined people to speak about
      the "NEW TUBERCULOSIS" of the third millennium. It had started from a number of
      393 patients suffering from pulmonary tuberculosis and age over twenty. This
      people were in hospital between 1997-2000 at the Pneumophysiology section in the
      Caracal's Municipal hospital. They were grouped after this parameters: the
      disease type, sex, environment, occupation, beginning form, clinic form,
      bacteriologic exam BK, diagnosis delay, lesion stretch and associated diseases,
      looking to discover the profile which is the most frequently used which satisfies
      in high percentage many of the studied parameters. We underline that the HIV test
      was negative to all the new cases and readmitted positive at T3 and to all the
      sick people who were registered with therapeutic failure in 1997 and 1999, so the
      AIDS impact with tuberculosis in this zone was null. Also systematic in the last
      two years we made ABG at relapses, failures and chronic; the bacillus resistance
      was not put in evidence, thing also hard to accept. The profile the most
      frequently met no matter the environments life, disease type, sex, age is the
      fibro-cases-cavitary farm (50%) followed by the infiltrative one (35%) with an
      "classic" onset in more than two third of the cases, bilaterally of the injures
      and the diagnosis delay with at least two months at 60% from all cases and a
      positively of the sputum in microscopy of about 50%. At least one third of the
      sick people are unemployed. This profile has of course epidemic consequences an
      therapeutic especially.

PMID- 12043271
TI  - [Specific features of acute renal failure in patients treated with rifampicin].
AB  - This retrospective study was performed on 92 patients diagnosed with acute renal
      failure (ARF) post discontinuous rifampicin treatment, admitted between 1974
      2000, in Hemodialysis Center of 1st Timisoara Clinical County Hospital. The
      passage from the continuous treatment (7/7) to discontinuous RMP treatment
      triggered the ARF in 77 patients and the restart of the treatment after one year
      or more of treatment arrest, lead to ARF in 15 cases. The ARF symptomatology
      appeared in the first 12 hrs of treatment resumption in 14.13% cases and in
      85.87% after 38.5 +/- 8.2 hrs. The most frequent symptoms were lumbar pain in
      76.08%, nausea and vomiting in 60.86%, abdominal pain (52.17% of cases) flu-like
      (fever, chills, myalgia), jaundice, diarrhea, hypotension, confusion and
      hypertension in only 7.6% of cases. In 94.56% of cases renal symptoms appeared in
      normal kidneys. The renal injury evolution was favorable, with significant
      improvements after 20 days in serum and urine biological parameters. The
      antibodies anti-RMP were present in serum 55.43% of patients, in 80.39% of them,
      the presence of antibodies was related to high values of gamma-globulins. In
      33.69% of patients sterile leukocyturia, considered a marker of interstitial
      nephritis, was present. The most frequent associated ARF complications were the
      hemolytic anemia emphasized by high levels of unconjugated bilirubin and positive
      Coombs' test in 93.3% of patients, and liver injuries, present in 41.69% of
      cases. Thrombocytopenia was registered in 27.7% of cases, infections in 28.6%,
      gastrointestinal complications in 11.95%, and cardiovascular complications in
      9.78% of cases, these severe forms leading to the death of patients. The ARF post
      discontinuous rifampicin treatment presents a favorable evolution even when it is
      associated with other organ or systems complications. The ARF and associated
      complications are due to the specific immune system activation by rifampicin, and
      by direct toxic effects of rifampicin at tissues level.

PMID- 12043273
TI  - [The child in tuberculosis hotbeds].
AB  - The city of Cluj-Napoca and the Cluj County, once situated in the comfortable
      zone of tuberculosis incidence, below the country, average, have registered a
      permanent and alarming increase in the both adult and child incidence of
      tuberculosis the last 5 years, which made us find the analysis of the phenomenon
      useful and constructive--having in view children mainly. Therefore we started to
      study all the adult bacillary hotbeds, bacteriologically confirmed in the city
      (150, totaling 172 cases) and having in contact between 1995-2000 with 280
      children; superposing period of the 1995-2000. Antituberculosis National
      Programme reviewed in 1997. Statistical correlation between clinical forms of
      tuberculosis identified in children has been analyzed as well as aspects
      connected to: sources (number, contagiousness, intimacy of contact etc),
      epidemiological inquiry, intradermoreaction, groups of age, bacteriological
      confirmation (of adults and children), X-ray aspects, B.C.G, treatment (place of
      application, regime), prophylaxis. In spite of the growing incidence, the
      clinical forms of tuberculosis registered in children have been benign, no death
      registered and a positive evaluation after a year (90% achieved healing and
      treatment) which demonstrates a good epidemiological, therapeutical and
      prophylactic covering of a pediatric cases from the patent hotbeds of adult
      tuberculosis, but which must be completed and sustained by a socio-economical and
      better cultural context.

PMID- 12043274
TI  - [Respiratory disorders during sleep in COPD patients].

PMID- 12043275
TI  - [Aspects of etiology and pathophysiology of sleep apnea syndrome].

PMID- 12043276
TI  - [Considerations of basic and clinical research in respiratory disorders induced
      by asbestos].

PMID- 12043277
TI  - [First experiences of non-invasive positive-pressure ventilation at home in
      chronic respiratory failure in Romania].
AB  - The authors are describing the first two cases of noninvasive positive pressure
      ventilation at home from our country, applied for chronic respiratory failure,
      demonstrating the advantages and modalities of approach to tackle this new
      concept of treatment.

PMID- 12043278
TI  - [Recurrent pleural effusion revealing a left atrial myxoma].
AB  - A 43 years old woman without any medical history was admitted 8 months before
      with a right pleural effusion, considered and treated as tuberculous pleurisy,
      with a good evolution. The recurrence of the right pleural effusion, the
      reappearance of chest pain, anxiety and nocturnal dyspnea elicited new
      investigations. The pleural fluid had a low protein content, pleural biopsy was
      irrelevant. CT scan, bronchoscopy and abdominal ultrasound were of no diagnostic
      value. Cardiac ultrasound revealed a large left atrial tumor, determining mitral
      stenosis. The patient underwent surgery, the tumor was excised, the histologic
      type was myxoma. Three weeks after surgery a right pleural effusion was noticed,
      this time with high protein content and resolving with non-steroid anti
      inflammatory treatment. Pleural effusion never reappeared in the following 6
      months. Discussions are made upon the mechanism which determined the pleural
      effusion in this case.

PMID- 12043280
TI  - [Digestive disorders with respiratory expression].

PMID- 12043279
TI  - [What is your diagnosis? What supplemental investigations would you recommend?
      What is the best attitude?].

PMID- 12043281
TI  - [Importance of bronchographic examination in the diagnosis of respiratory
      disorders].

PMID- 12043283
TI  - [Tuberculosis in the first year of the third millennium in Romania].

PMID- 12043282
TI  - [Nicotine dependence and smoking cessation].

PMID- 12043284
TI  - [Malignant melanoma of the uvea. Current status and prospects].

PMID- 12043285
TI  - [Prognostically relevant markers of malignant melanoma of the uvea].
AB  - In addition to classic risk factors such as tumor size, tumor location, and
      histological cell type, a range of other potentially prognostic parameters have
      been discovered in the past few years. Many of these have only been described
      once so that they cannot be considered established markers. A few, however, such
      as vascular patterns or monosomy 3, were independently identified by several
      groups and now constitute recognized prognostic markers. The association of these
      factors with the disease course provides us with ever-new insights into the
      biology of this tumor. In particular, with the aid of new technologies such as
      microarray analysis, researchers around the globe hope that new and exciting
      discoveries will be made that can also modify therapy concepts.

PMID- 12043286
TI  - [Choroid melanoma. Adjuvant therapy in high risk patients and new therapy
      approaches in the metastatic stage].
AB  - The treatment modality of primary uveal melanoma has up to now had no direct
      influence on the evolution of metastatic disease. Novel adjuvant treatment
      modalities are being developed on the basis of identifying significant prognostic
      factors for survival. The development of vaccination protocols targeting specific
      melanoma and/or tumor antigens has gained increasing importance and is currently
      being evaluated. Up to date the median survival of patients with metastases of
      uveal melanoma used to be approx. 5 months. In the last years median survival of
      selected patients with metastatic disease could be increased to 14 months by
      intrahepatic fotemustin influsions. Novel systemic chemotherapy protocols are
      currently being evaluated based on chemosensitivity studies. Furthermore,
      immunotherapeutical modalities are entering clinical evaluation as treatment for
      metastatic uveal melanoma.

PMID- 12043287
TI  - [Endoscopic resection of malignant melanomas of the uvea after preoperative
      stereotactic single dose convergence irradiation with the Leksell gamma knife].
AB  - In cases of large volume and highly prominent melanomas of the uvea, it is rare
      for conventional methods of radiation therapy to enable salvage of the globe or
      even residual functionality of the affected eye. Complications due to the massive
      amount of accumulated necrotic tissue often necessitate subsequent enucleation of
      the blinded eye. Tumor-destroying, single-dose convergence irradiation
      (radiosurgery) of such tumors applied shortly before endoresection can represent
      a possible therapeutic alternative in these types of cases.

PMID- 12043288
TI  - [Reproducibility of measuring retinal nerve fiber density. Comparison of optical
      coherence tomography with the nerve fiber analyzer and the Heidelberg retinal
      tomography device].
AB  - BACKGROUND: Glaucoma is associated with a progressive loss of retinal ganglion
      cell axons and the evaluation of the thickness of the retinal nerve fibre layer
      (RNFL) is important for early diagnosis and follow-up. Results of RNFL thickness
      measurements may vary according to the devices used. Therefore, the present study
      has analysed and compared the reproducibility of data obtained with three
      different instruments. METHODS: RNFL thickness was determined using a circular
      identification line around the optic nerve head by optical coherence tomography
      (OCT), a Heidelberg Retina Tomograph (HRT) and a Nerve Fiber Analyser (NFA). Each
      eye was tested six times. The values for RNFL thickness were calculated for the
      superior, inferior, nasal and temporal areas. A one-way analysis of variance with
      random effects was chosen to estimate the variance components. The intraclass
      correlation coefficient (ICC) as a measure of reliability and the coefficient of
      variation (CV%) as a measure of precision were determined to estimate the
      reproducibility of RNFL thickness measurements. RESULTS: With all three
      instruments, the reproducibility of measurements between the superior, inferior,
      temporal and nasal areas did not differ significantly suggesting that
      reproducibility does not depend on the thickness of the RNFL. Data obtained by
      NFA showed the highest ICC values (0.9) and lowest CV% values (7.0), followed by
      those obtained by HRT (reliability ICC 0.8; precision CV% 12). A markedly lower
      degree of reproducibility was found for the OCT compared to NFA and HRT
      (reliability ICC 0.5; precision CV% 15). CONCLUSION: The comparison of RNFL
      thickness measurements with OCT, NFA, and HRT showed that the NFA yielded the
      most reliable results followed by HRT.

PMID- 12043289
TI  - [Microsurgical quality assurance exemplified by cataract surgery].
AB  - BACKGROUND: The new German laws demand comprehensive quality assurance in all
      hospitals. The prerequisite for this in ophthalmic microsurgery is the complete
      documentation of all relevant surgical details including patient comorbidity.
      METHODS: Since 1989 we have documented all microsurgical procedures using a
      computer-based surgery recording system. To analyze the changing spectrum of
      cataract surgery in a university eye hospital, we evaluated 12,653 consecutive
      cataract extractions divided into 5 periods between 1990 and 1999. RESULTS:
      Within these periods the patients' age changed significantly (p < 0.001), whereas
      the gender showed no significant change (p = 0.34). Furthermore, there was an
      increase in the number of simultaneous surgical procedures (p < 0.01) as well as
      the frequency of the pseudoexfoliation syndrome (p < 0.001). In addition the mean
      duration of cataract procedures decreased (p < 0.001) and the occurrence of
      vitreous loss also decreased (p < 0.001). CONCLUSIONS: Long-term documentation of
      all relevant patient data enables valid evaluation of the patient spectrum.
      Furthermore, this monitoring helps to manage the challenge of quality assurance
      in ophthalmology.

PMID- 12043290
TI  - [Results of surgical management of abducens paralysis].
AB  - BACKGROUND: The pre- and postsurgical results after mono- and bilateral
      transposition surgery for abducens nerve palsy are reported. PATIENTS AND
      METHODS: In 13 eyes from 11 patients with 6th nerve paralysis, transposition
      surgery modified after Kaufmann was performed after a median duration of 13
      months (range 6-28 months). The actual angle of strabismus, the capability of
      abduction and the field of binocular single vision with the tangent screen
      according to Harms were measured prior to surgery, immediately after surgery (1-3
      weeks) and in the later postsurgical period (9-12 months). RESULTS: Of the
      patients 7 achieved fusion with binocular single vision, 5 of these patients had
      to accept an ocular torticollis of 10 degrees (range 5-15 degrees) and 4 patients
      had a tendency to exclusion. Of the 11 patients, 9 were treated successfully with
      one single surgical procedure 2 of which had bilateral abducens nerve palsy and 2
      patients needed 2 further operations. The median preoperative convergent angle in
      the primary position was reduced from 28 degrees (range 16 degrees-60 degrees) to
      a median angle of 0 degree, sometimes only latent (range D 7 degrees-C 4 degrees)
      in the late postoperative period. The median postoperative abduction over the
      midline was 10 degrees (range 3 degrees-25 degrees). CONCLUSIONS: Bilateral 6th
      nerve paralysis was treated effectively with simultaneous transposition surgery
      in both eyes. In most cases an additional weakening of the medial rectus muscle
      was not necessary. An initial overcorrection with exotropia in the early
      postoperative period is desired and is a predictive factor for a good late
      postoperative result.

PMID- 12043291
TI  - [Acute peripheral vestibular lesions. Monocular subjective visual vertical and
      cyclodeviation].
AB  - BACKGROUND: A deviation of the subjective visual vertical (svv) is often found in
      patients with unilateral peripheral vestibular lesions and in most cases the
      deviation is transitory and easy to compensate. The purpose of the study was to
      find out if there is a correlation between deviation of the svv and objective
      cyclodeviation of the retina. PATIENTS AND METHODS: A total of 20 patients (10
      females and 10 males aged between 16 and 78 years) with acute vestibular disease
      were enrolled. Only patients with a binocular deviation of the svv of more than 2
      degrees and/or a difference between the monocular deviation of more than 1.5
      degrees were included. The svv was examined monocular in a darkened room and
      after pupil dilatation, fundus photography was performed on each eye. The angle
      between papilla and macula was measured manually. RESULTS: We found a good
      qualitative correlation between svv (mean 7.9 degrees) and objective
      cyclodeviation (mean 10.6 degrees). CONCLUSION: In contrast to the binocular
      measurement of the svv, we found good correlation between the monocular svv and
      the objective cyclorotation measured with fundus photography. It is not yet clear
      which part of the vestibular system is responsible for cyclodeviation. Because of
      our results we recommend monocular measurement of the svv in clinical
      examinations.

PMID- 12043292
TI  - [Final clinical indications and etiology in 1,023 enucleations. Descriptive
      databank evaluation with SPSS software in variable response mode with dummy
      variables].
AB  - BACKGROUND: A new data bank developed for ophthalmopathology using a computer
      generated, multidigital data code is expected to be able to accomplish complex
      clinicopathologic correlations of diagnoses and signs, as provided by (multiple)
      clinical events and histopathologically proven etiologies, and to facilitate the
      documentation of new data. PATIENTS AND METHODS: In the ophthalmopathology
      laboratory 2890 eyes were examined between January 20, 1975 and December 12,
      1996. The main diagnoses and patient data from this 22-year period were recorded.
      To facilitate the presentation of data, a 10-year period with eyes of 976
      patients enucleated from December, 1986 to December, 1996 was chosen. Principal
      and secondary diagnoses served for establishing the data bank. The frequencies of
      successive histologic and clinical diagnoses were evaluated by a descriptive
      computing program using an SPSS-multi-response mode with dummy variables and a
      categorical variable listing of the software (SPSS version 10.0) classified as
      (a) non-filtered random, (b) filtered by multiple etiologies, and (c) filtered by
      multiple events. RESULTS: The principal groups (e.g., histologic diagnoses
      concerning etiology) and subgroups (e.g., trauma, neoplasia, surgery, systemic
      diseases, and inflammations) were defined and correlated with 798 separate
      diagnoses. From 11 diagnoses/events ascribed to the clinical cases, 11,198
      namings resulted. CONCLUSIONS: Thus, a comparative study of complex etiologies
      and events leading to enucleation in different hospitals of a specific area may
      be performed using this electronic ophthalmopathologic data bank system. The
      complexity of rare disease and integration into a superimposed structure can be
      managed with this custom-made data bank. A chronologically and demographically
      oriented consideration of reasons for enucleation is thus feasible.

PMID- 12043293
TI  - [Color vision defects in patients with arterial hypertension].
AB  - PURPOSE: In view of the generally impaired vascular condition in patients with
      arterial hypertension, we were interested in their colour perception. METHODS:
      Patients (n = 35, f:m = 14:21, mean age 52 +/- 11 years) with arterial
      hypertension without damage in end-organs and normal subjects (n = 62, :m =
      28:34, mean age 49 +/- 9 years) as a control group were included in this study.
      Exclusion criteria were other systemic or ophthalmological diseases. In addition
      to the ophthalmological examinations (visual acuity, refraction, intraocular
      pressure, slit lamp and fundus examination) the colour vision was tested by the
      colour arrangement test Roth 28-hue (E) desaturated under standard conditions:
      The background used was black cardboard, illuminated by two Osram fluorescent
      lamps (L36 W/12LDL Daylight) providing 2000 lux at the test table. RESULTS: The
      ophthalmological examinations in the patients and in the control group were
      normal. The patients with arterial hypertension had a significantly higher mean
      error score (median +/- mean absolute deviation 150 +/- 56, Mann-Witney U-test: p
      < 0.001) in the colour arrangement test than the control group (median +/- mean
      absolute deviation 72 +/- 53.4). A particular colour axis (blue-yellow or red
      green) was not found. CONCLUSION: Although the ophthalmological examinations were
      normal we found a disturbed colour vision in patients with arterial hypertension.
      This has to be taken into account in colour vision testing to avoid diagnostic
      interferences between specifically ocular diseases (e.g. glaucoma) and arterial
      hypertension.

PMID- 12043294
TI  - [Psoriasis and hypogonadism in chronic blepharokeratoconjunctivitis. A case
      report].
AB  - BACKGROUND: Ocular symptoms occur in approximately 10% of patients with psoriasis
      vulgaris. PATIENT: We report the clinical course of a 35-year-old male patient
      with obstructive meibomian gland dysfunction, keratoconjunctivitis and reduced
      reflex secretion of both eyes. Psoriasis vulgaris and hypothalamic hypogonadism
      were also present. Genetic testing (cytogenetic and DNA analysis) was performed
      because of additional facial dysmorphia, brachydactylia and obesity. No
      chromosomal anomaly was found and no genetic syndrome has yet been diagnosed. The
      therapeutic regimen included preservative-free artificial tears, occlusion of the
      puncta and a systemic dose of doxycycline. Dermatological symptoms were treated
      topically and the hypogonadism was treated with intramuscular injections of
      testosterone. CONCLUSION: Lacrimal and meibomian glands are influenced by
      androgens. Therefore hormonal dysfunction can also have contributed to the
      blepharokeratoconjunctivitis in this patient.

PMID- 12043295
TI  - [New automated microkeratome for trepanation of lamellar keratoplasty].
AB  - BACKGROUND/PURPOSE: Lamellar keratoplasty is an established therapy of corneal
      pathologies without endothelial involvement and the lack of endothelial rejection
      is one of the major advantages compared to penetrating keratoplasty. The major
      disadvantages of manually prepared lamellar corneal grafts are the limited
      mechanical and optical quality but the automated lamellar therapeutic
      keratoplasty system ALTK (MORIA) is intended to overcome these disadvantages. The
      purpose of this preliminary work is to investigate histologically and in clinical
      cases, if the ALTK system can achieve this aim. PATIENTS AND METHODS: Corneas
      from two human donors were cut with a 300 microns trephine. After fixation, the
      stromal bed and the excised cup of one specimen were stained with PAS and
      examined by light microscopy and the other specimen was analyzed by scanning
      electron microscopy. In addition, follow-up data of two patients who received
      such a lamellar graft are reported for the first 9 and 7 months postoperation,
      respectively. RESULTS: The lamellar cut of homogeneous depth revealed only minor
      stromal trauma. Both clinical cases demonstrated only minimal interface haze
      during follow-up. Despite a remarkably clear cornea, visual acuity improved only
      slowly because the precise lamellar cut tended to partially reproduce any
      preexisting irregular astigmatism. CONCLUSIONS: The ALTK system simplifies and
      standardizes the trephination of lamellar corneal grafts but a longer follow up
      is necessary with respect to visual development and preservation of a clear
      graft.

PMID- 12043296
TI  - [Transient unilateral amaurosis. Optic nerve compression in paranasal sinus
      mucositis].

PMID- 12043297
TI  - [Postoperative complication after cataract operation. Early postoperative
      capsular block syndrome, caused by viscoelastic Healon 5].

PMID- 12043298
TI  - [Differential eyelid tumor diagnosis. I].

PMID- 12043299
TI  - New approaches to improving patient safety.

PMID- 12043300
TI  - Gartner lists top 10 e-health issues for 2002.

PMID- 12043302
TI  - Splash pages that make more than a ripple.

PMID- 12043301
TI  - Group Health docs not overwhelmed by Web-based patient communications.

PMID- 12043303
TI  - Getting your FAQs right.

PMID- 12043304
TI  - [Caspases and apoptosis: die and let live].
AB  - Apoptosis (genetically programmed cell death) plays a key role in human
      physiology and pathogenesis of various diseases, including cancer. A suicide of
      cell can be initiated by many different factors, but activation of caspases,
      which are a special class of proteolytic enzymes, is always involved in this
      process. Activation of caspases may be achieved by several molecular pathways:
      the best known stimuli triggering caspase cascade are stimulation of Fas or TNF
      receptors, release of cytochrome c from the cellular mitochondria and exposure to
      granzymes, which are secreted by cytotoxic T cells. Activated caspases digest
      many cellular proteins responsible for cell cycle regulation (e.g. RB, MDM2), DNA
      damage recognition and repair (e.g. DNA-PK, P53, PARP), and regulation of the
      cellular structure (e.g. actin and lamins). All these functional and structural
      protein modifications lead directly to apoptosis. Further research on the
      mechanisms controlling caspase activity and the modes of action will provide
      better insight into pathogenesis of cancer and other disorders. It may be even
      the first step to design new and more efficient methods of conventional tumor
      treatment or gene therapy.

PMID- 12043305
TI  - [Genetic aspects of Marfan syndrome].
AB  - Pathological changes of skeleton, circulatory system and eye--typical for Marfan
      syndrome--were described in the article. Collagen abnormalities were discussed as
      well as contemporary knowledge concerning the inheritance of the syndrome.
      Special attention was paid to the gene FBN1 localized on chromosome 15 and its
      influence on fibrilline 1 synthesis. Another gene responsible for abnormality of
      fibrilline 2 is FBN2 localized on chromosome 5. The mutations (over 140) of above
      mentioned genes were shortly described.

PMID- 12043306
TI  - [Incidence of selected bacterial pathogens of the respiratory tract in patients
      with bronchial asthma].
AB  - Chronic bacterial infections intensify the reactivity of bronchi and aggravate
      the course and the control of asthma. They cause the disorders of both function
      and the structure of respiratory epithelium. Not only structural elements of
      bacteria but also their toxins intensify the release of mediators of the
      inflammatory reaction (leucotriens, histamine, IL1, IL4, IL6, IL8, TNF alpha).
      The aim of our research is to determine the prevalence of microorganisms, which
      can have an influence on the course of asthma. Moraxella catarrhalis has been the
      most frequent isolated pathogen (23.7%) in patients with bronchial asthma. We
      have received only individual isolations of Streptococcus pneumoniae and
      Haemophilus influenzae strains. Bacterial flora of the upper respiratory tract in
      patients with bronchial asthma has been more diverse in comparison with
      microflora of airways in healthy subjects. The significant percentage of Candida
      isolation in asthmatics (over 30% in bronchial tree secretion) poses the high
      risk of incidence of mycotic complications of inhaled steroids. In patients with
      asthma bronchial tree secretion is more valuable diagnostic material than
      pharyngeal swab.

PMID- 12043307
TI  - [Case report for POEMS syndrome].
AB  - The objective of this paper was the description of a case of male patient with
      POEMS syndrome. POEMS syndrome is characterized by simultaneous appearance of
      polyneuropathy, the enlargement of internal organs, endocrinopathy, monoclonal
      gammapathy and skin changes. In discussion the diagnostic difficulties and the
      therapeutic problems were emphasized.

PMID- 12043308
TI  - [Course of pregnancy in a patient with systemic lupus erythematosus--case
      report].
AB  - Authors describe a successful pregnancy outcome after prednisone and aspirin
      therapy in 19-year-old woman with systemic lupus erythematosus with the history
      of recurrent urinary tract infections, pericarditis and encephalitis.

PMID- 12043309
TI  - [Metastasis of renal carcinoma to the diaphragm].
AB  - The most common sites of metastases originating from primary renal clear cell
      carcinoma are bones and lungs. The authors present a rare case of the tumor that
      metastasized to the diaphragm. Both lesions, the primary in the kidney and the
      secondary in the diaphragm, were detected occasionally during the ultrasound
      examination of the right pleural cavity and abdominal cavity.

PMID- 12043310
TI  - [A case of postmenopausal hyperandrogenism caused by a lipid cell tumor].
AB  - Steroid-secreting neoplasms of the ovary and adrenal gland comprise a small group
      of tumors. A 76-year-old woman presented hair loss, facial hirsutism associated
      with increased serum total testosterone level. The adrenal glands and the ovaries
      were normal on radiological and ultrasonographic investigation. The patient was
      submitted to a pelvic exploratory laparotomy. Hysterectomy and salpingo
      oophorectomy were performed. A solid and circumscribed ovarian tumor of 2 cm in
      diameter was found. The pathological diagnosis was lipid cell tumor with stromal
      hyperplasia. The purpose of this report is to relate how difficult is to
      establish the diagnosis and the origin of the hyperandrogenism in a patient with
      normal image studies.

PMID- 12043311
TI  - [Microflora of gastric juice in patients after eradication of Helicobacter pylori
      and treatment with a proton pump inhibitor].
AB  - Previous studies have suggested that decrease of acidity of gastric juice leads
      to microbial overgrowth in gastric juice. AIM OF THE STUDY: Qualitative and
      quantitative evaluation of upper respiratory tract and gastric juice microflora
      depending on the change of gastric juice pH, which occurred during treatment with
      pantoprazole and eradication therapy. MATERIAL AND METHODS: 40 patients suffering
      from duodenal ulcer or reflux esophagitis have been examined. Group 1, patients
      without infection of H. pylori have received pantoprazole 40 mg/d for 4 weeks.
      Group 2, patients with infection of H. pylori have received 7-day eradication
      therapy (pantoprazole, amoxicillin, clarithromycin) and then pantoprazole 40 mg/d
      for 3 weeks. The samples of gastric juice have been taken twice: before treatment
      and in the 4th week of treatment. The assessment of gastric juice included pH
      measurement and bacteriological analysis. RESULTS: The mean values of gastric
      juice pH in the group 1 were as following--1.7 (SD +/- 0.53) before and 5.2 (SD
      +/- 2.26) during the treatment. Mean microbial counts were: 0.47 (SD +/- 1.01)
      logCFU/ml before, and 1.77 (SD +/- 1.48) logCFU/ml during the treatment. In group
      2 the increase of approximate amount of gastric juice from 1.8 (SD +/- 0.77)
      before treatment to 3.8 (SD +/- 2.43) during the treatment was noticed. The
      average titer of gastric juice microflora increased from 0.5 logCFU/ml (SD +/-
      0.83) to 1.39 logCFU/ml (SD +/- 1.52). Similarity between microflora isolated
      from gastric juice and tonsil swabs was noticed among most of the patients.
      CONCLUSIONS: The increase of gastric juice pH during the treatment with
      pantoprazole can lead to microflora growth in gastric juice. Microorganisms
      isolated from gastric juice among patients treated with antisecretive drugs
      mainly derived from the upper respiratory tract. Mostly isolated strains were: S.
      aureus, E. coli, Candida albicans.

PMID- 12043312
TI  - [The influence of isosorbide mononitrate on skin blood flow in patients with
      Raynaud's syndrome].
AB  - The influence of isosorbide mononitrate on skin blood flow in the pulp of finger
      by means of laser-Doppler flowmetry was evaluated in 19 women with Raynaud's
      syndrome. Skin blood flow changes were measured after cooling the hand.
      Isosorbide mononitrate decreased the influence of cooling on skin blood flow in
      the pulp of finger. This finding supports the theory that endothelial dysfunction
      is one of the reasons of Raynaud's syndrome. We suppose that application of
      isosorbide mononitrate should be useful in prevention and the treatment of
      Raynaud's phenomenon attacks.

PMID- 12043313
TI  - [Levels of hyaluronic acid in chronic viral C hepatitis with relationship to
      liver steatosis].
AB  - Hialuronic acid, important element of extracellular matrix, plays a significant
      role in liver fibrosis. The aim of the work is to evaluate serum hialuronic acid
      concentrations in patients with chronic viral C hepatitis (CHC) and in patients
      with alcoholic liver steatosis in correlation with liver morphology and classic
      liver function tests. MATERIAL AND METHODS: The study group consisted of 38
      persons: 17 with CHC, including 8 with coexisting steatosis, 8 with alcohol liver
      steatosis and 13 healthy subjects as a controls. Hialuronic acid (HA) was
      measured in serum with the use of enzyme-linked binding protein assay, produced
      by Chugai Diagnostics Science Co., Japan. RESULTS: The highest mean HA
      concentration was found in CHC patients with steatosis (95.5 +/- 40.3 ng/ml) and
      it was significantly higher than among controls (56.9 +/- 17.8 ng/ml). The
      biggest necrosis and inflammation changes and fibrosis were observed in this
      group. HA concentration in alcoholic liver steatosis was insignificantly higher
      than among healthy controls (72.8 +/- 45.8 ng/ml). The lowest concentrations of
      HA were found in CHC patients without steatosis (32.9 +/- 9.8 ng/ml). CONCLUSION:
      There is correlation between serum HA concentration and liver fibrosis.

PMID- 12043314
TI  - [Cold retrograde brain perfusion in repair of aortic arch dissection or
      aneurysm].
AB  - We have used hypothermic retrograde brain perfusion (RBP) as a cerebral
      protection concurrently with hypothermic circulatory arrest (HCA) since September
      1994. Till January 2000, 59 patients with ascending and arch aortic aneurysms
      were operated on (32 emergency cases with acute aortic dissection, 27 elective,
      including 5 with the chronic dissection). Cardio-pulmonary bypass (CPB) was
      established, using a common femoral artery and two venous caval cannulae, general
      hypothermia, aorta cross-clamping, and cold crystalloid intermittent cardioplegia
      via the coronary orifices. In 10 patients with De Bakey type I dissection, in
      whom the intimal tear was localised either in the arch or high in the ascending
      aorta near the orifice of the brachiocephalic trunk, and in 1 patient without
      dissection, after implementing HCA, continuous RBP was carried on with cold
      oxygenated blood via the superior caval cannula from its additional connection
      with the arterial line. After accomplishing the distal anastomosis (in 6 cases
      with the top of the arch containing the orifices of the brachiocephalic arteries
      and upper descending thoracic aorta, in 1 case using artificial arch, in 4 cases
      before the orifice of the brachiocephalic trunk) RBP was finished and CPB re
      established. The incompetent aortic valve was repaired by suspension of its
      commissures and the prosthesis was anastomosed proximally above the coronary
      orifices. Seven patients died, one (with megaaorta syndrome) during the
      operation, 2 of myocardial failure on the 2nd postoperative day, and 3 of
      multiple organ disorder (including stroke with hemiparesis in 2) in the 2nd
      postoperative week (all but one after regaining consciousness). One patient died
      suddenly at home six weeks after the operation. Four patients are alive, without
      any neurological damage. CONCLUSION: This simple and economical method
      effectively protects the brain against ischaemia and emboli, without technically
      prolonging or complicating the operation.

PMID- 12043315
TI  - [Evaluation of analgesic action of fluvoxamine compared with efficacy of
      imipramine and tramadol for treatment of sciatica--open trial].
AB  - At present time tricyclic antidepressants (TA) are important tools in therapy of
      chronic pain. However administration of TA produce a number of side effects.
      Antidepressants of new generation, selective serotonin reuptake inhibitors (SSRI)
      induce less side effects in patients than TA. The aim of the study was to
      estimate an analgetic effect of antidepressant of new generation--fluvoksamine
      (Fevarin) in treatment of ischialgia and comparison with an analgetic effect of
      impramine and tramadol--opoid receptors antagonist. 70 patients with sociatic
      neuralgia were included to the research. They were at random divided into three
      groups. First one was treated with tramadol consisted of 22 persons (18 men and 4
      women, average age--42.9 y.), second one treated with impramine consisted of 24
      persons (18 men and 6 women, average age--43.2 y.) and third one treated with
      fluvoksamine consisted of 24 persons (15 men and 9 women, average age--42.3 y.).
      Observation time was 19 days. Pain intensity was evaluated in four degree
      descriptive scale. Before and after treatment clinical symptoms of depression
      were estimated in groups of patients treated with impramine or fluvoksamine by
      Zung's Depression Scale. There were no statistically significant differences in
      analgetic effect after treatment with fluvoksamine or impiramine. There was
      meaningly few number of side effects in the group treated with fluvoksamine.
      CONCLUSION: Fluvoksamine and impramine have similar effectiveness in treatment of
      ischialgia, that is why fluvoksamine should be considered as medication when TA
      are contraindicated.

PMID- 12043316
TI  - [The value of determining vaginal secretion reaction (pH) as a screening test of
      bacterial vaginosis].
AB  - The reaction of vaginal fluid was performed in 386 women admitted to the
      Outpatient Clinic. In 120 (31.09%) cases pH value was more than 4.5. The
      frequency of abnormal results grew with the age of patients; lower percentage was
      observed in pregnant women, more educated ones and nulliparas. Much lower
      diagnostic specificity of the vaginal fluid reaction was noticed in
      postmenopausal women what was confirmed in the test on the presence of aromatic
      amines and clue cells in microscopic examination. The correct reaction (it means
      pH lower than 4.5) practically exclude the bacterial vaginosis.

PMID- 12043317
TI  - [Echocardiographic evaluation of right ventricular structure and diastolic
      function in patients with overweight and arterial hypertension].
AB  - The accelerated development of the left ventricular dysfunction due to increased
      preload and afterload is often observed in patients with systemic hypertension
      and concurrent overweight/obesity. Right ventricle is also influenced by systemic
      hypertension. The aim of the study was the echocardiographic assessment of the
      right ventricular structure and diastolic function in patients with systemic
      hypertension and overweight. The study group consisted of 31 subjects with
      untreated, mild to moderate systemic hypertension and overweight defined as a
      body mass index (BMI) above 26 kg/m2. Right ventricular diastolic diameter and
      right ventricular wall thickness were similar in study and control groups. In
      comparison with the controls patients with overweight demonstrated significantly
      shortened acceleration time of systolic flow in pulmonary artery, increased mean
      pulmonary artery pressure and decreased early to late filling wave velocity time
      integrals. These findings indicate that systemic hypertension associated with
      obesity does not cause additional morphological changes of the right ventricle
      compared to hypertensives with normal weight. Impaired right ventricular
      diastolic filling and pulmonary artery systolic flow indicate the presence of
      mild right ventricular dysfunction in subjects with overweight, however,
      diastolic and systolic parameters are within normal range both in patients with
      normal weight and overweight.

PMID- 12043318
TI  - [Multimodal evoked potentials for evaluation of diabetic encephalopathy].
AB  - The consequences of chronic diabetes mellitus in the brain are less known than
      peripheral nerves lesion. Despite of the progress in research the connections
      between these consequences and metabolic or vascular disorders which accompany
      diabetes are not univocally determined. The aim of the study is assessment of
      conduction in central afferent tracts and the velocity of blood flow in pre- and
      intracerebral arteries in patients chronically treated because of diabetes
      mellitus. We examined 63 diabetic patients at the age 48.9 +/- 12.9, treated with
      hypoglycaemic drugs for 13.5 +/- 8.2 years. The symptoms of cranial diabetic
      neuropathy (CDN) mainly in the form of eyeball motor disturbances were observed
      in 26 patients. The others had neither signs of central nervous system lesions
      nor other chronic disease. We estimated patient clinical condition of visual
      evoked potentials [VEP(s)], brainstem auditory evoked potentials [BAEP(s)]
      latency, somatosensory evoked potentials [SSEP(s)] and evaluated ultrasonically
      the mean blood flow velocity in pre- and intracerebral arteries. It was
      ascertained that the patients with CDN were older and their treatment duration
      was shorter. Moreover diabetes mellitus type 2 (76.9% p < 0.001) and insufficient
      metabolic control of the disease (80.8% p < 0.001) were significantly more
      frequently found in this group. The latencies of assessed multimodal evoked
      potentials [MEP(s)] in all patients were significantly longer than in the control
      group. In patients with CDN the lengthening of SSEP(s) latency occurred
      significantly more frequently than in the other patients. Diabetic retinopathy,
      arterial hypertension and the changes in blood flow velocity in pre- and
      intracerebral arteries were more frequently noted in the subgroup of patients
      with CDN. The difference in flow velocity in pre- and intracerebral arteries
      between both examined groups was significant. CONCLUSIONS: 1. High frequency of
      lengthened MEP(s) latency in patients suffering from diabetes indicates the
      presence of subclinical diabetic encephalopathy. 2. Cranial diabetic neuropathy
      not necessarily influence on central conduction time assessed by the EP method.
      3. Diabetic encephalopathy seems to be dependent both on metabolic disorders and
      vascular changes.

PMID- 12043319
TI  - [The fate of children from Piekary Slaskie with elevated lead concentration in
      blood].
AB  - The aim of this work is to evaluate the influence of the long-term lead-poisoning
      on children's health, achieved education level and social maturity in their youth
      and adult life. The work is based on the material collected in the Environmental
      Health Outpatient Clinic in Piekary Slaskie. The researches were carried out on
      the base of a questionnaire filled in by adults who had the average lead
      concentration in blood of 27.4 micrograms/dl +/- 9.8 micrograms/dl when they were
      7-15 years old in the period of 1986-1989. All examined subjects were inhabitants
      of Piekary Slaskie since their birth. The questionnaires were submitted to 90
      persons but only 36 responded. There were at the age of 16-26 having the
      technical, secondary or academic education. Statistical significance was stated
      only in the field of interdependence between the education level of parents of
      the surveyed group and the grades achieved by the subjects in primary school. No
      statistical significance was shown when comparing the lead concentration in blood
      in children aged 7-15 and education level achieved during next 10 years of their
      life, their health condition at the age of 16-26 and other parameters. The
      parents of the surveyed group (with high lead concentration in blood at the age
      of 7-15) have been the inhabitants of Piekary Slaskie since their birth.
      Therefore we can make a presumption about the double-generation environmental
      influence of lead concentration on the grades achieved in primary school by the
      surveyed persons.

PMID- 12043320
TI  - [Difficulties with using T lymphocyte culture as a method for diagnosing
      allergies to benzylpenicillin].
AB  - The activation of T lymphocytes upon antigen stimulation plays a crucial role in
      adverse immune responses including drug-specific hypersensitivity reactions. The
      helpfulness of conventional tritiated thymidine incorporation assay for
      penicillin allergy diagnostics is limited. Benzylpenicillin, as a reactive
      compound, constitutes typical example of hapten. Most of research on penicillin
      hypersensitivity use benzylpenicillin-albumin (BPO-HSA) conjugates. Thus in this
      study we describe an in vitro proliferation assay with benzylpenicillin or
      penicillin and autologous serum protein conjugates. Interestingly these
      conjugates enhanced incorporation of tritiated thymidyne, when benzylpenicillin
      did not exert an influence on PBMCs proliferation (correlation coefficient r = 
      0.0119). This so-called carrier-effect indicates that benzylpenicillin and serum
      globulin complexes can take part in penicillin allergy (primary immune response).
      Optimal secondary response is obtained when the benzylpenicillin bind the same
      carrier for both primary and secondary immunization. Father-proliferation assay
      with modification of responses to phytohaemagglutinin by benzylpenicilloilated
      serum protein results in significant decrease of incorporation of [3H] thymidyne.
      Otherwise benzylpenicillin did not modify postmitogenic proliferation of PBMCs.
      Our findings indicate that the use of penicillin and autologous serum protein
      conjugates is helpful. This study show the manner in which benzylpenicillin forms
      T-cell epitopes.

PMID- 12043321
TI  - [Contemporary role of scintigraphy in diagnosis, and evaluation of radioiodine
      therapy for treatment of thyroid diseases].
AB  - The paper presents a short historical outline and contemporary use of
      scintigraphic studies of thyroid gland. Appropriate recommendations and correct
      interpretations of the results of routine thyroid scans and the usefulness of
      other scintigraphic studies with 111In-octreoscan, 99mTc-MIBI, 99mTc-DMSA, 18FDG
      and radiolabeled monoclonal anti-carcinoembryonic antigen antibodies were
      discussed in the light of the present thyroid diagnostic studies. Particular
      attention was paid to the dependence of the scintigraphic thyroid images upon the
      thyroid-stimulating hormone (TSH) level in the patient's serum. The chosen
      examples of scintigraphic studies show the advantages of scintigraphic evaluation
      of efficacy of radioiodine therapy. The most often mistakes of the scintigraphy
      interpretations were showed.

PMID- 12043322
TI  - Euthanasia--at a moment of truth.

PMID- 12043323
TI  - Amoebic liver abscess: a comparative study of needle aspiration versus
      conservative treatment.
AB  - BACKGROUND: Amoebic liver abscess is a serious problem in Pakistan. Its
      management includes antimicrobial drugs, needle aspiration and surgical drainage.
      This study was done to see the therapeutic efficacy, safety and outcome of
      ultrasound guided needle aspiration of amoebic liver abscess combined with
      antiamoebic drugs. METHODS: This was a prospective study with a minimum follow up
      of six months comparing the results of needle aspiration plus antiamoebic drugs
      with drug treatment alone in Amoebic Liver Abscess. It was carried in Surgical
      'B' Unit of Ayub Teaching Hospital from July 1998 to June 2001. The patients were
      divided into two groups. Group A with abscess < 300 cm3 were treated with drugs
      alone. Group B patients with abscess > 300 cm3 or smaller abscesses which failed
      to respond to medical treatment were treated with both needle aspiration and
      drugs. Main outcome measures were abdominal pain, fever, anorexia, hepatomegaly,
      resolution of amoebic liver abscess on ultrasound, length of hospital stay and
      any complications. RESULTS: There were 46 patients in the study group. 21 (45.5%)
      patients were in Group A and 25 (54.5%) in Group B. The ages ranged from 15-70
      years. 38 patients were male and 8 were females. The right lobe was involved in
      44 (95.5%) patients and left lobe in 2 (4.5%) patients. Mean volume of abscess in
      Group A was 225 cm3 and in Group B was 560 cm3. Needle aspiration was successful
      in 24 (96.3%) patients and failed in 1 (3.7%) patient. The mean time of clinical
      improvement was 7 and 3 days respectively in Groups A and B. The mean hospital
      stay was shorter in Group B (3.5 day) than Group A (7.5 days). The resolution of
      abscess seen on ultrasound was rapid in Group B. Complications occurred in only
      one patient in Group B. No mortality was seen in any group. CONCLUSIONS: Needle
      aspiration combined with antiamoebic drugs is more effective than drug treatment
      alone in the management of amoebic liver abscess.

PMID- 12043324
TI  - Sensitivity and resistance of antibiotics in common infection of male and female.
AB  - BACKGROUND: There is increasing concern regarding antimicrobial resistance in
      Pakistan. Data are limited on the prevalence, pattern of resistance and risk
      factors associated with resistant organisms. This Study was done to address these
      issues as they relate to common infection of male/female. METHODS: Different
      clinical materials collected from 100 patients admitted in hospital or who
      attended out door clinic were used. Antibiotics like Enoxabid, Fortum, Ceporex,
      Klaricid, Maxaquin, Zenacef, Ceporexin, Urixin, Septran, Keflex. Erythrocine,
      vibramycin and tetracycline were used for culture sensitivity. RESULTS: It was
      observed that most of the pus specimens received are from females and urine
      specimens from males. Specimen of pus contains mostly Staph aureus, Urine
      specimen contain mostly E. coli whereas Pseudomonas pyrogenosa and proteases were
      also observed in urine, pus, sputum and ascitic/pleural fluids of patients. Among
      all drugs that were used, Enoxabid, Ceporex were vary sensitive against strains
      of Staph and Pseudomonas present in specimen. Strains of proteases were resistant
      against these drugs. Urixin and Septran show mixed action. In comparison of
      Enoxabid, Ceporex and Ceporexin, Zenocef and Fortum show sensitivity in fewer
      cases of Staph and E. coli. Mexaquin shows a good sensitivity against Pseudomonas
      and E. coli. It was observed that Septran, Erythrocine, Vibramycin, Tetracycline,
      Klaracid and Keflex are not very good acting drugs in infection of urine, pus,
      sputum and fluids. Finding of a low but definite level of resistance to septran,
      erythrocine, Vibramycin, Tetracycline, Klaracid and Keflex is important for
      selection of empiric therapy for infection.

PMID- 12043325
TI  - Comparison of population survey of Multan about cigarette smoking with survey of
      Abbottabad.
AB  - BACKGROUND: There are different pollutions in the environment e.g. Water
      pollution, dust pollution, pollen pollution, noise pollution and smoking
      pollution. As smoking from different sources is a pollution and injurious to
      health therefore we decided to conduct epidemiological study of smoking in
      Multan. METHODS: The study was carried out on 1100 subjects residing in different
      localities of Multan. A specifically designed questionnaire was filled and the
      responses computed. The results were then compared with similar survey conducted
      in Abbottabad and reported earlier. RESULTS: Out of the study population 40.02%
      were found to be smoking different kinds of tobacco. Out of 442 smoking persons
      36.66% are smoking for just company while 57.01% for anxiety and remaining for
      other reasons. 20-40 cigarettes of different brands per day are used by different
      occupation persons. The expenditure for cigarette smoking is in the range of
      Rs:300-2000 per month. Among smoking persons 292 (66.06%) complained of Nocturnal
      cough, 96 (21.72%) during day and 54 (12.22%) at both time. 125 smokers (28.28%)
      complained of sputum, while 43 subjects (9.73%) complained of occasional or
      frequent blood stained sputum. 24 (5.43%) smokers reported of symptoms or
      diagnosis of Ischeamic heart disease. 35 smokers (7.92%) smoke during fasting of
      Holy Ramazan. 290 smokers (65.61%) do not hesitate to smoke at public places.

PMID- 12043326
TI  - Clinical versus C.T. scan diagnosis in stroke--a comparative study of 50 cases.
AB  - BACKGROUND: Cerebrovascular disease is one of the three leading causes of death
      in the world along with cancer and heart disease. Differentiation between
      cerebral infarction and intracerebral haemorrhage is important because now a days
      proper management of the acute stroke syndrome is based on the correct diagnosis
      of the pathological type. This study compared clinical and C.T. scan diagnosis of
      stroke and determined the reliability of the clinical diagnosis in cases of
      stroke. METHODS: This study was conducted on 50 patients of stroke at
      Postgraduate Medical Institution, Lady Reading Hospital, Peshawar from Jan 1995
      to May 1996. Clinical diagnoses were made in conformity with criteria for
      clinical diagnosis of intracranial haemorrhage, cerebral infarction due to
      embolism or thrombosis. The clinical diagnosis was then compared with the CT
      diagnosis. RESULTS: We found that from careful history and clinical examination
      differentiation could be made between cerebral infarction and haemorrhage. In our
      study at Government Lady Reading Hospital, cerebral hemorrhage accounted for 42%
      of cases of stroke and cerebral infarction in 58%. CONCLUSIONS: In order to make
      a clinical diagnosis of stroke, a detailed history and thorough clinical
      examination is mandatory. As far as treatment planning is concerned clinical
      diagnosis of stroke is not safe enough as a guide for anticoagulant or
      thrombolytic therapy. In order to confirm the aetiological diagnosis of stroke
      one must rely on C.T. scan examination.

PMID- 12043328
TI  - Role of Islam in prevention of smoking.
AB  - BACKGROUND: Smoking is common all over the world. It is a pandemic pollution. In
      spite of awareness about its dangerous effects on the health, tobacco companies
      spend million of dollars on its advertisement and sales promotion. This study
      tried to see the effect of Islam on prevention of smoking. METHODS: The study was
      carried out on 1000 subjects residing in different localities of Abbottabad. The
      basic method used was a questionnaire designed specifically to give an idea of
      the religious status of person and correlate that with their smoking habits.
      RESULTS: Out of the study group 325 (32.5%) were found to be indulged in
      different kinds of smoking and we concluded that Islam has a positive effect on
      smoking prevention.

PMID- 12043327
TI  - Effect of examination stress on blood cell parameters of students in a Pakistani
      medical college.
AB  - BACKGROUND: Physiological studies show that stress can alter the blood cells
      parameters in healthy individuals. We tried to determine whether exams in medical
      schools are stressful enough to produce such changes. METHODS: A randomized
      selection of female students from Women Medical College, Abbottabad, Pakistan,
      was carried out. After preliminary medical checkup blood samples were taken
      before and during exams. Students having temperature or high blood pressure at
      the start of study were excluded. Finally 37 students were included. Estimations
      of red blood cells, hematocrit, neutrophils, lymphocytes, eosinophils, monocytes,
      basophils and platelets were carried out. RESULTS: Compared with pre-examination
      results the blood samples taken during exams showed a significant decrease in
      eosinophil, basophil, lymphocyte and monocyte count. An increase in platelet and
      neutrophil count was also observed. No significant changes were observed in red
      blood cell and hematocrit readings. CONCLUSION: It is concluded that examinations
      in medical schools are stressful enough to produce changes in blood cells
      parameters which include increase in neutrophils, and platelets, while
      eosinophils, monocytes basophils and lymphocytes decreased in number.

PMID- 12043329
TI  - Serum vitamin A levels in children under five years old.
AB  - BACKGROUND: Vitamin A deficiency is considered to be a wide spread public health
      problem among preschool children in the developing countries. A pilot study for
      the nutritional problems in Pakistan showed that majority of the children in the
      study group was suffering from vitamin A deficiency. METHODS: This study was
      carried out to assess the vitamin A status of children under five belonging to
      different socioeconomic groups. They were divided into two groups. Their weight
      for age criterion fell within the reference range set by Pakistan Pediatric
      Association in accordance with National Center for Health Statistics. The vitamin
      A levels were determined spectophotometrically by using trifluoroacetic acid.
      RESULTS AND CONCLUSION: The results suggested a significant difference in the
      levels of Vitamin A in children belonging to high and low socioeconomic groups,
      suggesting the role of socioeconomic factors in determining the vitamin A status
      of the body.

PMID- 12043330
TI  - Awareness about balanced food among unskilled human resource.
AB  - BACKGROUND: This study was carried out at Peshawar about the food habits of daily
      wages labourers working in the urban area. METHODS: One to one interview was
      conducted with 50 randomly selected daily wages labourers, using structured
      questionnaire. At the same time specimen of capillary blood was obtained from
      their fingers tips for haemoglobin measurement. RESULTS: The study revealed that
      due to lack of awareness and poor socio economic status the daily wages labourers
      are more prone to malnutrition and iron deficiency anaemia. CONCLUSION: There is
      a need of comprehensive health education and a strategy should be designed to
      provide a food locally available that could fulfill the requirement that occurs
      due to the deficiency of animal protein in the food of daily wages labourers.

PMID- 12043331
TI  - Schwann cells: leader of Nervenkitt.

PMID- 12043332
TI  - Presentation of pulmonary tuberculosis at Ayub Teaching Hospital Abbottabad.
AB  - BACKGROUND: Pulmonary tuberculosis (PTB) may be easily confused with other chest
      diseases during its initial presentation. This study was carried out to identify
      presenting clinical and laboratory features that differentiate PTB from other
      diseases and to correlate clinical features and laboratory findings. METHODS:
      This study was carried out at the Department of Pulmonology, Ayub Teaching
      Hospital Abbottabad, from September 1999 to December 2000. A total of 46 patients
      were included in the study after being clinically diagnosed as pulmonary
      tuberculosis. These patients were subjected to detailed history taking recording
      age, sex, weight, socioeconomic status and smoking habits. They were clinically
      evaluated and laboratory tests including Hemoglobin, ESR, TLC, DLC and sputum for
      AFB were done. They were put on standard antituberculous therapy and followed
      from 2 to 5 months to monitor treatment effect. Statistical analysis was
      performed by SPSS 8 computer program. RESULTS: A bimodal presentation (below age
      30 years and above age 50 years), fever, productive cough, weight loss, night
      sweats and raised ESR were the most common findings in PTB patients. Sputum AFB
      smears were positive in 50% of diagnosed cases. No correlation was found between
      clinical and laboratory parameters in establishing a confident diagnosis of the
      disease. CONCLUSIONS: The study highlights the importance of further research to
      pinpoint stronger and more reliable criteria for diagnosis.

PMID- 12043333
TI  - A clear moment. An unexpected embrace leads an emergency physician to a renewed
      sense of purpose.

PMID- 12043334
TI  - Life in medicine's fast lane. Emergency physicians thrive on the unexpected.

PMID- 12043335
TI  - Darkness and light.

PMID- 12043336
TI  - Easing the grief at ground zero.

PMID- 12043337
TI  - Caring for the caregiver.

PMID- 12043339
TI  - Foreign exchanges.

PMID- 12043338
TI  - Great needs.

PMID- 12043341
TI  - Language interpreter services in outpatient settings. Responsibilities and
      resources.

PMID- 12043340
TI  - Unrecognized torture affects the health of refugees.
AB  - Recognizing the symptoms and signs of torture and documenting their cause may be
      key to providing effective health care for refugees from countries where torture
      is known to have occurred. Generalist or primary care physicians are in a unique
      position to establish a trust relationship with patients, to identify potential
      signs and symptoms of torture, and encourage patients to talk about their
      experiences. With knowledge about, understanding of, and sensitivity toward
      torture survivors, physicians can help these patients regain their health and a
      sense of well-being.

PMID- 12043342
TI  - The MMA Alliance--putting words into action.

PMID- 12043343
TI  - Communicating uncertainty.

PMID- 12043344
TI  - Quality care. All want it; let's define it.

PMID- 12043345
TI  - Healing after horror. Joseph Wester Meyer, M.D., Ph.D., helps survivors recover
      from the psychological wounds of trauma.

PMID- 12043346
TI  - Screening--a cruel deception.

PMID- 12043347
TI  - Individualising hormone replacement therapy.

PMID- 12043348
TI  - Advances in women's health.

PMID- 12043349
TI  - Managing diabetes in pregnancy.

PMID- 12043350
TI  - Long-acting progestogen contraceptives.

PMID- 12043351
TI  - The patient with recurrent miscarriage.

PMID- 12043352
TI  - Giving health advice to travellers.

PMID- 12043353
TI  - Managing fever and febrile convulsions in children.

PMID- 12043354
TI  - When to say what: trustees and the media.
AB  - If your organization were suddenly thrust into the media's glare, and you were
      called upon for comment, would you know how to handle it? Does your board have a
      media game plan? It's important that trustees decide, before media attention
      hits, who speaks on what issues to which audience.

PMID- 12043355
TI  - Facility planning. How design can improve quality and lower costs.
AB  - Since construction and design costs can consume a significant portion of a
      hospital's budget, it makes sense to try and anticipate future needs. If your
      facilities haven't been updated in many years, you'll be pleased to learn the
      positive impact that design can have on care delivery.

PMID- 12043357
TI  - Leadership and governance: what's Enron got to do with it?

PMID- 12043356
TI  - Rebuilding physician-hospital relationships.

PMID- 12043358
TI  - Side by side. Communication is key to a successful side by side CEO-board chair
      partnership.
AB  - Great partnerships require hard work, and that goes double for the health care
      board chair and CEO, whose relationship is complicated by a whole host of issues.
      But the effort will pay off in organizational success. One essential element:
      frequent, two-way communication.

PMID- 12043359
TI  - 2000 CDC Growth Charts for the United States: methods and development.
AB  - OBJECTIVES: This report provides detailed information on how the 2000 Centers for
      Disease Control and Prevention (CDC) growth charts for the United States were
      developed, expanding upon the report that accompanied the initial release of the
      charts in 2000. METHODS: The growth charts were developed with data from five
      national health examination surveys and limited supplemental data. Smoothed
      percentile curves were developed in two stages. In the first stage, selected
      empirical percentiles were smoothed with a variety of parametric and
      nonparametric procedures. In the second stage, parameters were created to obtain
      the final curves, additional percentiles and z-scores. The revised charts were
      evaluated using statistical and graphical measures. RESULTS: The 1977 National
      Center for Health Statistics (NCHS) growth charts were revised for infants (birth
      to 36 months) and older children (2 to 20 years). New body mass index-for-age
      (BMI-for-age) charts were created. Use of national data improved the transition
      from the infant charts to those for older children. The evaluation of the charts
      found no large or systematic differences between the smoothed percentiles and the
      empirical data. CONCLUSION: The 2000 CDC growth charts were developed with
      improved data and statistical procedures. Health care providers now have an
      instrument for growth screening that better represents the racial-ethnic
      diversity and combination of breast- and formula-feeding in the United States. It
      is recommended that these charts replace the 1977 NCHS charts when assessing the
      size and growth patterns of infants, children, and adolescents.

PMID- 12043360
TI  - [The future of pathology--from the viewpoint of clinical pathology].
AB  - Pathology is one of the fundamental diagnostic fields of medicine, its position
      has changed and will undergo transformation in the 21st century due to the
      introduction of new methods. Theoretically, pathology was based upon 3 pillars:
      1. the autopsies, 2. the surgical pathology, i.e. the processing and evaluation
      of different biopsies and surgically resected specimens and 3. the cytological
      investigations. The autopsy was the dominant field till the end of the seventies
      of the 20th century but about the turn of the 20th and 21st century the cytology,
      first of all the fine needle aspiration cytology took over the leading role in
      the pathologic diagnostic activity. This displacement resulted in such a high
      decrease in the number of autopsies that it is impossible to conclude appreciable
      epidemiological statements. Meanwhile the role and position of the pathologist
      has changed also substantially. Previously he was regarded often as a prosecuting
      attorney. At present time this opinion is transformed into clinical pathologist.
      Errors in the histopathological diagnosis and reporting can occur in the surgical
      pathology but its number is not high. To detect and to avoid them is attainable
      by composition of an adequate audit-system. The number of the new investigatory
      methods is increasing nowadays wide-spreadingly in the medicine and so in the
      pathology too. The immunocytochemistry is regarded already as a conventional
      method but the PCR and FISH-technique are applied also on a large scale. At the
      same time, new tools such as the cDNA microarray technology, the micro-chip based
      analytical chemistry, the laser capture microdissection and the wireless medical
      information appear also in the pathology. The modern information technology is
      impacted more intensively into the day-to-day pathological work. This method
      enables to develop worldwide communicating systems which can make perfect the
      diagnostic work. The pathologist has traditionally functioned as a medical
      consultant to the clinician. The predominant function of the pathologist has to
      be evolved from that of medical consultant to that of information specialist.

PMID- 12043361
TI  - [Role of percutaneous tracheostomy in intensive care: a review].
AB  - INTRODUCTION: Performing early tracheostomy is a possible solution during
      prolonged ventilation in order to decrease late complications. Considering the
      duration of procedure and the hazards concerning the patient transport the risk
      of operation is high in the critically ill patients. Therefore bedside
      percutaneous tracheostomy (PCT) plays an increasing role in intensive therapy.
      AIMS: For emphasizing the widening role of PCT in intensive care the procedures
      were analysed in the mirror of international experiences. After introducing short
      history of the procedure the improvement of techniques is presented. METHODS: A
      description of the experiences with the three main techniques is presented based
      on early original publications. Analyzing the results of comparative studies the
      risks and benefits of different methods were investigated in focus of the early
      and late complications. RESULTS: Comparing the percutaneous and surgical
      techniques significantly lower number of late complications were observed in PCT
      groups by several studies but there is a debate concerning the early hemorrhagic
      complications. Among the percutaneous techniques there was no significant
      difference between the occurrence of complications. The greatest experience has
      been gathered with the sequential dilatation technique. The duration of procedure
      was the only significant difference between the sequential and forceps
      dilatational technique. CONCLUSIONS: According to the international literature
      the percutaneous tracheostomy is the procedure of choice for prolonged airway
      management for high-risk intensive care patients. Concerning the elevated risk of
      operation the percutaneous techniques have significantly shorter duration and
      lower rate of late complications. Among the different percutaneous techniques the
      only significant difference was the duration of the procedure. The shortest
      procedure was the forceps dilatational technique.

PMID- 12043362
TI  - [Extracorporeal shock wave lithotripsy of pancreatic stones as a part of complex
      endoscopic therapy].
AB  - INTRODUCTION: The authors report on ESWL treatment of 29 patients suffering from
      pancreatolithiasis. PATIENTS/METHODS: The mean age was 46.5 (23-76) years, there
      were 7 women and 22 men. The etiology of chronic calcifying pancreatitis was
      alcohol in 24 (82.7%) cases, idiopathic in 3 (10.3%) patients and there was one
      familiar and one pancreas divisum case. The indication of ESWL was abdominal pain
      in 27/29 (93.1%) cases. During ERCP pancreatic sphincterotomy was performed and a
      nasopancreatic catheter was placed for a continuous lavage with isotonic citrate
      at a rate of 0.5-1 ml/min for a mean of 6 days. The mean number of ESWLs was 2.2.
      RESULTS: Fragmentation was achieved in 28/29 (96.5%) patients. There were five
      (17.5%) complications, fever in three cases, one case of acute relapse of
      pancreatitis, and one hematuria. The mean number of therapeutic ERCPs was 2.32 (0
      7). Overall a complete duct clearance was achieved in 62% (18/29) of the
      patients, partial clearance in 13.9% (4/29) but the ESWL was unsuccessful in
      24.1% (7/29) of the cases. Early pain relief occurred in almost every case
      (28/29). Twenty four (82.7%) patients were followed for 18.7 (2-33) months. Each
      patient remained symptom free. The average weight gain was 7.6 kg. The exocrine
      pancreatic function determined by Lundh test in 7 patients had not improved (11.2
      vs. 12.2 pathological value in average). Recurrence of pancreatic duct stones was
      revealed in four (22.2%) cases among the 18 successfully treated patients after
      15 (7-22) months. CONCLUSION: The authors conclude that the ESWL treatment of
      pancreatic stones together with the endotherapy applied is an effective method
      for painful pancreatolithiasis.

PMID- 12043363
TI  - [Paroxysmal nocturnal hemoglobinuria].
AB  - The current knowledge of the history, clinical course, diagnosis and treatment of
      Paroxysmal Nocturnal Hemoglobinuria (PNH) are summarized in this article.

PMID- 12043364
TI  - [Correlations of alternative medicine, health status and health care in Hungary].
AB  - INTRODUCTION: Alternative medicine has a growing popularity in Hungary as well as
      in other Western countries. However, we are in lack of accurate empirical data on
      the use of this kind of care and its relationship toward official health care
      system. AIMS: This paper focuses on the questions of the use of, prospective
      willingness to use, and attitudes toward alternative medicine with regard to the
      demographic background, general health status and habits of visiting doctors.
      METHOD: The source of data is a Baranya county health survey from 1999 (N =
      2357). The statistical method of analysing data is regression analysis. RESULTS:
      Alternative medicine is popular mostly in groups of people with younger age,
      higher level of education and income. Preferring alternative care is connected to
      having more chronic, non-fatal illnesses while the number of fatal illnesses on
      one hand and activity restriction on the other have no significant role. Positive
      relationship to alternative medicine is connected to more overall visits of
      doctors but less of GP-s. CONCLUSIONS: Regarding the demographic background and
      health status alternative medicine in Hungary appears similar to what
      publications from Western countries have already enlighted. Data on utilization
      of official health care can refer to the possibility that alternative medicine
      might serve as an alternative of primary care but not of secondary care.

PMID- 12043365
TI  - [Performance of Thallium 201 rest-redistribution spect to predict viability in
      recent myocardial infarction].
AB  - BACKGROUND: The detection of viability after acute myocardial infarction is
      primordial to select the most appropriate therapy, to decrease cardiac events and
      abnormal remodeling. Thallium201 SPECT is one of the radionuclide techniques used
      to detect viability. AIM: To evaluate the use of Thallium201 rest-redistribution
      SPECT to detect myocardial viability in reperfused patients after a recent
      myocardial infarction. PATIENTS AND METHODS: Forty one patients with up to of 24
      days of evolution of a myocardial infarction were studied. All had
      angiographically demonstrated coronary artery disease and were subjected to a
      successful thrombolysis, angioplasty or bypass grafting. SPECT Thallium201 images
      were acquired at rest and after 4 h of redistribution. These results were
      compared with variations in wall motion score, studied at baseline and after 3 or
      4 months with echocardiography. RESULTS: The sensitivity of rest-redistribution
      Thallium201 SPECT, to predict recovery of wall motion was 91% when patient
      analysis was performed and 79% when segmental analysis was done in the culprit
      region. The figures for specificity were 56 and 73% respectively. CONCLUSIONS:
      Rest-distribution Thallium201 SPECT has an excellent sensitivity to predict
      myocardial viability in recent myocardial infarction. The data obtained in this
      study is similar to that reported for chronic coronary artery disease.

PMID- 12043366
TI  - [Seroprevalence of antibodies against hantavirus in 10 communities of the IX
      Region of Chile where hantavirus infection were diagnosed].
AB  - BACKGROUND: Thirty six cases of clinical Hantavirus Cardiopulmonary Syndrome
      occurred in the IX Region of Chile. Most of these patients were young males, farm
      or timber workers, who lived near the Andes Mountain chain. AIM: To conduct an
      epidemiological and serosurvey study to determine the seroprevalence of IgG
      antibodies against Hantavirus in the general adult population living in rural and
      urban areas of 10 endemic communities of the IX region of Chile. MATERIAL AND
      METHODS: A total of 400 subjects were included, 40 of each community, 20 rural
      residents and 20 urban residents, 20 males and 20 females. RESULTS:
      Seroprevalence was 7.5% in Melipeuco, 5.0% in Lonquimay, 2.5% in Curacautin, 2.5%
      in Pucon and 0.0% in the remaining communities. Seroprevalence was higher in
      rural population (2.5%) than in the urban areas (1%). All seropositive subjects
      worked in farms or forests and observed rodents near their homes or working
      places. Females were affected the same as males and no differences were observed
      between Chilean natives and Hispanics. CONCLUSIONS: Prevalence of Hantavirus
      antibodies correlated with the geographic zone (Andes Mountain chain), overgrowth
      of wild rodents and exposure to rodent-infested environments.

PMID- 12043367
TI  - [Diagnosis and follow up of 23 children with organic acidurias].
AB  - BACKGROUND: Propionic aciduria (PA) and Methymalonic aciduria (MMA) result from
      an inherited abnormality of the enzymes propionyl CoA carboxylase and
      methylmalonyl CoA mutase respectively. This produces marked increases in the
      amino acids methionine, threonine, valine and isoleucine (MTVI). Their clinical
      presentation can be neonatal or late onset forms. AIM: To report 23 children with
      organic acidurias. MATERIAL AND METHODS: Twenty three cases of organic acidurias
      diagnosed since 1980 (17 PA and 6 MMA) and followed at the Institute of Nutrition
      and Food Technology, are reported. RESULTS: The average age of diagnosis was 3.9
      days for the neonatal form and 8.3 months for the late onset form. The most
      frequent symptoms were hypotonia, lethargy and vomiting. Neonatal PA had mean
      ammonemias of 1089 +/- 678.3 micrograms/dl. The figure for MMA was 933 +/- 801.9
      micrograms/dl. Seven children were dialyzed and 30% died. 16 children are
      followed and 81.2% have normal weight for age. Seven children required
      gastrostomy because of anorexia and failure to thrive. The nutritional treatment
      is based on natural and artificial proteins without MTVI, with periodical
      controls, amino acid and ammonia quantification. Some patients were submitted to
      enzyme assays and molecular studies. CONCLUSIONS: An early diagnosis and a very
      strict follow up allows a normal development of children with organic acidurias.
      There is a relationship between prognosis and the presentation form, the
      nutritional status and the emergency treatment during acute episodes. The
      importance of the enzymatic and molecular studies is emphasized because they
      facilitate treatment, accurate diagnosis and allow an adequate genetic
      counseling.

PMID- 12043368
TI  - [How to attract more and better manuscripts to be published in Chilean biomedical
      journals].
AB  - A survey was addressed to 57 editors of Chilean biomedical journals, on how to
      attract more and better manuscripts to their journals. Thirty seven editors (65%)
      answered this survey. According to them the main motivation of Medical Societies
      for editing their own journals is to improve information acquisition. To
      communicate an experience, followed by getting credits in their curriculum vitae,
      were considered by the editors as the main motivations of authors to submit
      papers. The most frequent deficiencies of manuscripts received are:
      disorganization in their presentation and bad adherence to journal's requirements
      for submitting manuscripts. An improvement in the relationship between author
      editor-reviewer was mentioned by most of the editors, as the mechanism to be used
      to enhance the quality of the manuscripts. Only 14 editors (38%) agree in that
      there is a decrease in the number of original papers submitted. This decrease was
      attributed by most of them, to a high pressure for publishing in journals with
      the highest impact factor. Suggestions on how to improve the Chilean biomedical
      journals included: a) to professionalize editorial work and to increase
      meticulousness when reviewing manuscripts; b) to increase the recognition of
      articles published in Chilean biomedical journals, when applying for academic
      promotions or research grants and c) to create a "national impact factor".

PMID- 12043369
TI  - [Molecular characterization of resistance mechanisms to chloramphenicol in
      Shigella flexneri strains isolated from Chilean children with acute diarrhea].
AB  - BACKGROUND: Chloramphenicol is one of the therapeutic options for shigellosis,
      but resistance to this antimicrobial is increasing. AIM: To characterize
      molecular mechanisms conferring resistance to chloramphenicol (Cm) in Shigella
      flexneri strains isolated from Chilean children with acute diarrhea. MATERIAL AND
      METHODS: Thirty one Shigella filexneri strains, including 22 with the Cm
      phenotype were analyzed. Strains were tested for antimicrobial susceptibility by
      plate dilution and for the presence of an internal fragment of the cat gene
      encoding for chloramphenicol o-acetyl-transferase, by polymerase chain reaction
      and Southern blot analysis. RESULTS: All Cm strains had a minimal inhibitory
      concentration over 64 micrograms/ml and amplified the internal fragment of the
      cat gene. Southern blot analyses indicated that this gene was located in the
      bacterial chromosome. CONCLUSIONS: Resistance to chloramphenicol in this group of
      Shigella flexneri strains was mediated by a chromosomally located cat gene.

PMID- 12043370
TI  - [Current epidemiological situation of trichinosis in Chile. 1991-2000].
AB  - BACKGROUND: Human and animal trichinosis has been recorded in Chile since the
      late XIX century and is irregularly distributed along the country. From high
      rates of infection in the early 1900, the frequency of this parasitosis in man
      has progressively decreased. AIM: To describe and discuss the epidemiological
      situation of trichinosis in Chile during the decade 1991-2000. MATERIAL AND
      METHODS: Human infection was assessed using annual incidence and lethality
      reports provided by the Ministry of Health, periodic photostrichinoscopies in
      corpses of non selected individuals autopsied at the Medico Legal Service and
      periodic national serologic surveys. The advise of one of the authors in an
      epidemic that occurred in 1999 in the VIII Region was also used. Animal infection
      was assessed using the annual prevalence of infection in pigs slaughtered in
      abattoirs, furnished by the Ministry of Health. RESULTS: A total of 631 clinical
      cases with 4 deaths (0.6%) was recorded. A decline in the incidence, from 0.7 x
      100,000 in 1991 to 0.2 x 100,000 in 2000 was recorded. The higher frequency of
      the parasitosis was observed in the Metropolitan, VI, VIII and X regions.
      Although human trichinosis has been observed in all seasons, its frequency
      increases in close relation with the higher pork consumption in cold seasons
      (45.8% in winter and 37.5% in spring). There has been a decrease of infection
      rates in pigs from 0.17@1000 in 1991 to 0.04@1000 in 1998-2000. CONCLUSIONS: The
      incidence and prevalence of trichinosis shows a constant decline in Chile.
      Considering the geographical characteristics of Chile, it is possible that an
      undetermined number of pigs are home reared and butchered without veterinary
      control, constituting an important source of human trichinosis.

PMID- 12043371
TI  - [Sports and feeding behavior disorders].
AB  - BACKGROUND: People who work out could have an excessive concern for diet and body
      weight and thus be more prone to have eating disorders. AIM: To compare
      psychological and behavioral traits between subjects with clinically relevant
      eating disorders and subjects that work out regularly. SUBJECTS AND METHODS: The
      Eating Attitudes Test (EAT-40) and the eight items of the Eating Disorders
      Inventory were administered to 151 patients that fulfilled the DSM-IV diagnostic
      criteria for eating disorders and to 396 subjects who work out regularly in
      gymnasiums (136 males). RESULTS: Eighteen percent of subjects that worked out (5
      males and 67 females) scored within the pathological range in the EAT-40. These
      subjects were classified as having a subclinical eating disorder. When comparing
      the EDI scores of these subjects with those of patients with clinically relevant
      eating disorders, they had a similar Drive for thinness (p = 0.413), Body
      dissatisfaction (p = 0.365), Maturity fears (p = 0.190) and Perfectionism (p =
      0.907). Females had similar Interpersonal distrust (p = 0.709) scores. Males had
      similar Maturity fears (p = 0.119), Perfectionism (p = 0.253) and Interpersonal
      distrust (p = 0.767) scores. CONCLUSIONS: Subjects that work out regularly and
      have subclinical eating disorders, display similar drive for thinness, body
      dissatisfaction, immaturity and perfectionism traits, than patients suffering
      from clinically relevant eating disorders.

PMID- 12043372
TI  - [Characteristics of children and adolescents attended in a private psychiatric
      outpatient clinic].
AB  - BACKGROUND: There is a 7% up to 32% prevalence of psychiatric problems in the
      pediatric population. AIM: To study the epidemiological features of children and
      adolescents attended in a psychiatric outpatient clinic. MATERIAL AND METHODS:
      All admissions to a psychiatric outpatient clinic, of people aged 18 years old or
      less, during 1998, were reviewed. The causes of consultation and the diagnoses
      were classified according to diagnostic manuals (ICPC-WONCA and DSM-IV
      respectively), by three experienced psychiatrists. RESULTS: The files of 376
      patients were reviewed (200 males, mean age of females 12 years old, mean age of
      males 10.5 years old). Seventy three percent consulted spontaneously. The main
      causes of consultation were anxiety disorders and adolescence problems (28%). The
      main diagnoses were attention deficit disorder and disruptive behavior,
      adaptative problems, mood and anxiety disorders. There were gender differences in
      the diagnoses. Women attended a mean of 6.3 sessions and men attended a mean of 4
      sessions. Fifty nine percent abandoned treatment. CONCLUSIONS: There is a limited
      access to mental health care. The low compliance with treatments must be studied
      and improved.

PMID- 12043373
TI  - [In vitro susceptibility of streptococcus pneumoniae strains isolated from lower
      respiratory infections in Instituto Nacional del Torax (INT)].
AB  - BACKGROUND: The rising antimicrobial resistance of streptococcus pneumoniae,
      requires permanent surveillance. Antimicrobial treatments of invasive infections
      must be modified accordingly. AIM: To assess the in vitro antimicrobial
      susceptibility of streptococcus pneumoniae strains isolated from lower
      respiratory infections. MATERIAL AND METHODS: Seventy five strains isolated
      during three periods in consecutive years were studied. In vitro susceptibility
      towards penicillin, erythromycin and ceftriaxone was studied using E-test
      technique minimal inhibitory concentrations. RESULTS: Five percent of strains
      were penicillin resistant and 11% had an intermediate sensitivity. Erythromycin
      resistance was observed in 1.3% of strains. Eight percent of strains had an
      intermediate sensitivity towards ceftriaxone and no resistance was observed.
      Comparing susceptibility in the three studied periods, it remained low and
      stable. CONCLUSIONS: High and intermediate resistance of Streptococcus pneumoniae
      towards penicillin is less prevalent than in other countries. A close
      surveillance must be maintained (Rev Med Chile 2002; 130: 304-8).

PMID- 12043374
TI  - [Community acquired pneumonia. Report of 8 cases of severe pneumonia by serogroup
      1 Legionella pneumophila in Chile].
AB  - Legionella pneumophila is the second cause of severe community acquired
      pneumonia. In Chile, however, there are few reports of pneumonia caused by
      Legionella. We report eight patients (6 men, aged 42 to 72 years old) with
      community-acquired pneumonia caused by Legionella pneumophila serogroup 1,
      confirmed by the measurement of urinary antigen. Clinical presentation was
      characterized by fever or hypothermia (in one case), cough, dyspnea and
      neurological abnormalities in four patients. Cigarette smoking was the most
      frequently identified risk factor. All patients had at least one American
      Thoracic Society severity criteria. Complications observed were acute hypoxemic
      respiratory failure in seven patients, shock in four, renal failure in four and
      need for mechanical ventilation in three. No patient died.

PMID- 12043375
TI  - [Myocardial pyrophosphate uptake in cardiac amyloidosis: report of case].
AB  - We report a previously healthy 73 years old woman, who was hospitalised with
      increasing dyspnea and signs of congestive heart failure. Echocardiography showed
      a normal left ventricular cavity with increased echogenicity of its walls and
      severe pulmonary hypertension. A lung ventilation/perfusion scintigraphy
      concluded that there was a low probability for pulmonary embolism. Coronary
      angiography was normal. A restrictive cardiomyopathy due to amyloid deposits was
      suspected. Myocardial pyrophosphate scintigraphy showed intense pyrophosphate
      uptake in the left ventricle wall. An abdominal fat tissue biopsy was positive
      for amyloid deposits.

PMID- 12043376
TI  - [Tuberculosis bursitis: report of case].
AB  - We report a previously healthy 51 years old woman with a one year history of pain
      in the left hip associated with a mass without fever or local inflammatory
      changes. Magnetic resonance imaging located the mass in the medial gluteal
      muscle. The pathological examination of the mass disclosed unspecific
      inflammatory changes. Due to worsening of pain, a left throchanteric bursitis was
      diagnosed two weeks later and a throchanteric bursectomy was performed, obtaining
      a second biopsy. Aerobic, anaerobic and fungal cultures were negative. Lowenstein
      Jensen culture showed development of mycobacteria and a genetic probe confirmed
      the presence of Mycobacterium tuberculosis. The second biopsy also identified
      several granulomas with areas of caseation and the Ziehl-Nielsen stain was
      positive for acid fast bacilli. Osteoarticular tuberculosis, specially bursitis,
      should be suspected in the presence of chronic pain associated with swelling.

PMID- 12043378
TI  - [Falls and gait alterations in elderly].
AB  - There is a higher frequency of falls in the elderly than in young people, due to
      age related physiological changes in gait. There is a lower amplitude of pelvic
      movements that affects gait efficiency. Equilibrium is also disturbed since the
      trunk assumes the leadership of gait, displacing the pelvis. Many diseases of
      elderly individuals, such as Parkinson disease, spastic paraparesis,
      cerebrovascular accidents or neuropathies, further impair the gait. Therefore,
      after the age of 65, all falls must be considered symptomatic.

PMID- 12043377
TI  - [Recommendations for the management of hypertensive crisis. A Consensus document
      of the Chilean Society of Hypertension].
AB  - The management of severe hypertension in the emergency setting demands a careful
      evaluation of the different underlying clinical situations, and of the impending
      risk for the life of the patient or of acute organ damage. Hypertensive
      emergencies and urgencies have to be identified, and distinguished from chronic
      severe hypertension, a frequent presentation to the emergency services. A
      thorough clinical evaluation, and not the magnitude of the blood pressure
      elevation, should be the basis of the differential diagnosis; this will guide the
      setting required for treatment (intensive care unit, ward or ambulatory), the
      drugs of choice, as well as the velocity of blood pressure reduction. Special
      emphasis has to be given to the management of cerebrovascular accidents and
      severe preeclampsia, as the reduction of blood pressure entails a risk of
      hypoperfusion of critical territories as the brain and fetus respectively. A wide
      range of drugs permits a tailored treatment of a variety of clinical situations.
      Efforts have to be made to detect and manage chronic hypertensive patients in
      order to reduce the consultation load represented by severe hypertensives in
      emergency services, by preventing hypertensive crisis, in order to focalize on
      real situations of risk.

PMID- 12043379
TI  - [V Chilean Symposium of Biomedical Journal Editors].
AB  - In August, 2001, the Editors of over 40 Chilean journals in biological, medical
      and health issues were gathered in Santiago, Chile, by the Chilean Association of
      Biomedical Journal Editors, together with guest librarians from Chile and Brazil,
      in a 2-day symposium. The main topics discussed were: the educational role of
      biomedical journals in Chile; how can Chilean journals become included in
      international databases; requisites for authorship in scientific articles; how to
      attract more and better manuscripts; advantages and limitations of the peer
      review system; ethical problems and conflicts of interest in the editorial
      process; electronic tendencies in scientific publications. This was the fifth
      meeting on similar topics held in Chile, starting in 1972, and the interchange of
      experiences and opinions among editors, librarians and other experts was fruitful
      and stimulating.

PMID- 12043380
TI  - [Clinical importance of hypercholesterolemia].

PMID- 12043381
TI  - Probiotics and immunity. Introduction.

PMID- 12043382
TI  - The influence of yogurt/Lactobacillus on the innate and acquired immune response.

PMID- 12043383
TI  - The bifidobacterial and Lactobacillus microflora of humans.

PMID- 12043384
TI  - Probiotics in clinical conditions.
AB  - Probiotics are nonpathogenic microorganisms which, when ingested, exert a
      positive influence on the health or physiology of the host. Their mechanisms of
      action and effects are now studied using the same pharmacological approach as for
      drugs. This article summarizes and comments on evidence for the positive effects
      of probiotics in various clinical situations. Substantial evidence can be
      achieved when randomized controlled trials or meta-analyses show positive
      results. The clinical situations studied include prevention or treatment of
      antibiotic-associated disorders, gastroenteritis, and diarrhea, lactose
      intolerance, intestinal infections and colonization by pathogenic bacteria
      (including Helicobacter pylori and Clostridium difficile), traveler's diarrhea,
      irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic cancer,
      urogenital infections and tumors, allergy (especially atopic eczema),
      vaccination, and cholesterol lowering. Current probiotics have an excellent
      safety record--another topic discussed in this article.

PMID- 12043387
TI  - Perception versus reality.

PMID- 12043388
TI  - Research or payoff?

PMID- 12043385
TI  - Probiotics in the management and prevention of atopy.

PMID- 12043389
TI  - Current issues in work hours of house staff physicians.

PMID- 12043390
TI  - Proper prescription and monitoring of physical and occupational therapy.

PMID- 12043386
TI  - Probiotics and immune response.

PMID- 12043391
TI  - Short on shots.

PMID- 12043392
TI  - Living in fear. Physicians face mounting liability insurance crisis.

PMID- 12043393
TI  - Captive law firms.

PMID- 12043394
TI  - The big 4-0.

PMID- 12043395
TI  - Prenatal HIV testing in private OB-Gyn practices in Texas.
AB  - This study evaluates the prenatal human immunodeficiency virus (HIV) testing
      behaviors of private obstetrics and gynecology practitioners in Texas. A
      statewide telephone survey of 614 providers of prenatal care determined the level
      of HIV testing, how testing is offered, and patient acceptance of the test.
      Ninety-nine percent of the practices offered HIV testing to all their pregnant
      patients, and 96% of the practices included HIV testing in the routine panel of
      tests for pregnant patients. More than 95% of the practices reported that 10% or
      less of the women refused the test when offered it; 73% of the practices reported
      no refusals. Less than half of the practices, however, discussed HIV prevention
      topics, and only 29% of the practices referred high-risk pregnant patients for
      prevention counseling. Although private practices of obstetrics and gynecology
      report testing almost all their prenatal patients, survey results suggest that
      providers could improve their prevention and patient education practices.

PMID- 12043396
TI  - Blame the AMA leaders.

PMID- 12043397
TI  - AAPS is a better bet.

PMID- 12043399
TI  - [Hip fractures--is the osteoporosis prophylaxis on the correct course?].

PMID- 12043398
TI  - Let physicians write the rules.

PMID- 12043400
TI  - [Enuresis nocturna. Does alarm intervention help?].

PMID- 12043401
TI  - [Child orthopedics].
AB  - Children's fractures are a challenge to the treatment system, in that 17,000
      children are treated in Denmark each year. The true burden on patients and
      society is unknown. It is estimated that 1000 new-born infants are treated for
      hip instability in Denmark per year, and 30 are diagnosed late. Ultrasound
      scanning is recommended for secondary screening and selective screening of
      children at risk. Identification of acetabular dysplasia followed by surgical
      correction could be an important prophylactic measure, with a potential reduction
      in expenses to society. To some extent, congenital clubfoot is hereditary.
      Environmental factors are important, maternal smoking being one. Early operative
      treatment yields good results. There is a need for prospective registration.
      Perthes' disease is an idiopathic necrosis of the capital femoral epiphysis.
      Passive smoking is a significant factor. A young age (< 7 years) and limited
      necrosis carry a good prognosis, and active treatment can improve the prognosis
      for the other patients.

PMID- 12043402
TI  - [Piperacillin/tazobactam--Tazocin. A penicillin-based alternative to 3rd
      generation cephalosporins and carbapenems].
AB  - The antibiotic piperacillin/tazobactam has recently been licensed for use in
      Denmark. Piperacillin/tazobactam combines a well known beta-lactam antibiotitic,
      piperacillin, and an inhibitor of bacterial beta-lactamase, tazobactam. The
      combination of piperacillin and tazobactam compared to piperacillin alone has an
      expanded antimicrobial spectrum, which includes Klebsiellae, Escherichia coli,
      and Proteus vulgaris resistant to ampicillin, as well as beta-lactamase-producing
      Staphylococcus aureus. As piperacillin in itself possesses antimicrobial activity
      against streptococci, enterococci, and Pseudomonas aeruginosa, the antimicrobial
      activity of piperacillin/tazobactam indicates that the combination may constitute
      an alternative to third generation cephalosporins and carbapenems in the
      treatment of complicated intra-abdominal infections infections in critically ill
      patients and for the empirical treatment of acute neutropenic febrile patients,
      as indicated by clinical studies.

PMID- 12043403
TI  - [Osteoporosis prevention in general practice after hospitalization for hip
      fracture].
AB  - INTRODUCTION: The aim of the study was to assess: 1) the degree of osteoporosis
      preventative therapy initiated by general practitioners (GP) after
      hospitalisation for a hip fracture; 2) the GPs' opinion of osteoporosis
      preventative therapy, and their opinion on whether it should be initiated by the
      hospital or the GP; 3) the need for a reference programme. MATERIAL AND METHODS:
      The GPs of patients discharged after a hip fracture in 1997-1998, were sent two
      questionnaires: one concerning osteoporosis preventative therapy of the patient
      and one concerning the GPs' own opinion on prevention. RESULTS: A total of 107
      patients (80% women, 20% men) met the criteria of the study. Eighty-seven per
      cent were seen by their GP within six months of discharge, 16% were started on
      preventative therapy, which was: 53% calcium/calcium + vitamin D, 40% etidronate,
      and 27% estrogen. No one chose alendronate, raloxifen, or hip protector. Eighty
      four per cent were not treated, of these 18% did not want to be treated, poor
      patient compliance was expected in 11%, and 6% of the GPs did not find the
      scientific documentation convincing. Four per cent had been referred for a bone
      scan, and 2% to X-ray of the vertebral column. Of the GPs, 52% felt it should be
      the patients' own GP who started the therapy, 48% felt it should be the
      discharging hospital physician, 83% felt they were capable of treating this
      condition. Sixty-nine per cent of the GPs felt a need for a reference programme,
      96% wished to have access to refer patients for a bone scan. DISCUSSION: Only 16%
      were started on osteoporosis preventative therapy after a hip fracture. The study
      shows a need for better co-operation and communication between hospital
      physicians and GPs, and a need for a reference programme.

PMID- 12043404
TI  - [Positive experiences in connection with menopause].
AB  - INTRODUCTION: As a part of a larger study, "Menopause described from the woman's
      perspective," it was the aim to explore whether women have any positive
      experiences in relation to the menopause and, if so, the nature of these
      experiences. MATERIALS AND METHODS: In a questionnaire, sent to a random sample
      of 51-year-old Danish women, an open-ended question concerning the course of
      menopause was included. A qualitative approach was used in the analyses. RESULTS:
      Of 393 women who answered the open-ended question 194 women described positive
      aspects of the menopause. The total number of replies with a positive content was
      268. These varied from unspecific statements describing a period of well-being or
      simply of having no problems at all, and concrete descriptions which primarily
      dealt with the relief that menstruation had ceased with its associated problems,
      such as PMS and fear of pregnancy. Lastly, they dealt with the possibility of
      personal growth and freedom to concentrate on the women's own requirements.
      DISCUSSION: The positive aspects of the menopause are a relevant field to
      investigate further, quantitatively as well as qualitatively. It is recommended
      that, in counselling, doctors include positive aspects and women's own resources
      to avoid the use of medication and unintentionally inducing a feeling of illness
      at this time of life.

PMID- 12043405
TI  - [Fever and skin hemorrhages in children--is it meningococcal disease?].
AB  - INTRODUCTION: Our main aims were to establish criteria for early distinction
      between meningococcal disease and other conditions with similar clinical
      features, and to identify other causes of haemorrhagic rashes accompanied by
      fever. MATERIALS AND METHODS: This prospective study comprised 264 infants and
      children hospitalised with fever and skin haemorrhages. RESULTS: We identified an
      aetiological agent in 28%: 15% had meningococcal disease, 2% another invasive
      bacterial infection, 7% enterovirus infection, and 4% adenovirus infection. Five
      clinical variables discriminated meningococcal disease from other conditions on
      admission: skin haemorrhages of (1) characteristic appearance; (2) universal
      distribution and (3) a maximum diameter of > 2 mm; (4) poor general condition;
      and (5) nuchal rigidity. DISCUSSION: If any two or more of these clinical
      variables were present, the probability of identifying a patient with
      meningococcal disease was 97% and the false-positive rate was only 12%. This
      diagnostic algorithm did not identify children in whom septicaemia was caused by
      other bacterial species.

PMID- 12043406
TI  - [Functional training of enfeebled elderly in their own homes. A cross
      disciplinary and cross-sectorial model].
AB  - INTRODUCTION: Today it is a proven fact that rehabilitation of elderly people
      suffering from illness and loss of functional faculties helps. The very weakest
      group is unable to make use of existing offers of rehabilitation. The objective
      of the investigation was to develop and test a model for functional training of
      weak, elderly people in their own home. MATERIALS AND METHODS: The process was
      assessed in eight cases. The elderly were selected consecutively on discharge
      from two geriatric wards as those who could be rehabilitated, but who were too
      weak to undergo the usual process. Training was supported by the regular home
      help assigned to the old person and carried out under the supervision of a
      geriatrician and a physiotherapist. An external-qualitative evaluation of the
      programme is published elsewhere. RESULTS: In collaboration with the elderly
      people and the home help, the project team succeeded in forming and implementing
      a training scheme based on the expectations that the elderly people had to
      rehabilitation. Of the eight patients taking part in the investigation, five
      realised their wishes for a greater degree of mobility and for being able to get
      out-of-doors. DISCUSSION: The model developed, where the home help acts as the
      central figure in the implementation of the rehabilitation of enfeebled, old
      persons under the supervision of a physiotherapist and a geriatrician, is an
      interesting alternative to the existing programmes for rehabilitation of elderly
      people in their own home. The work should be investigated in monitored tests,
      with the focus on effectiveness and consumption of resources.

PMID- 12043407
TI  - [Gallbladder torsion].
AB  - We report two cases of gallbladder torsion, which were diagnosed
      intraoperatively. This rare condition should be suspected in elderly women with
      acute abdominal pain of unknown origin. The treatment is cholecystectomy.
      Promptly treated, the prognosis is good.

PMID- 12043408
TI  - [Bacteremia and meningitis caused by Streptococcus pneumoniae during treatment
      with azithromycin].
AB  - After absorption, azithromycin is concentrated intracellularly, with a
      correspondingly low serum concentration. A case of bacteriemia and meningitis
      caused by macrolide-sensitive Streptococcus pneumoniae during treatment with
      azithromycin is presented and discussed.

PMID- 12043409
TI  - [Improved surgery and radiotherapy cure more patients with rectal cancer].

PMID- 12043410
TI  - [Chemoprevention can hardly substitute for screening for colorectal cancer].

PMID- 12043411
TI  - [Genetic population screening--an ethical dilemma].

PMID- 12043412
TI  - [Genetic technology and biobanks explain disease mechanisms].

PMID- 12043413
TI  - [Improved methods for prenatal diagnosis of Down syndrome].

PMID- 12043414
TI  - [More specific analyses in neonatal screening using DNA techniques].

PMID- 12043415
TI  - [Genetic predisposition tests in adults can prevent illness].

PMID- 12043417
TI  - [Progressive aphasia. New data on an old phenomenon].
AB  - Progressive aphasias are distinct but infrequently recognized clinical
      expressions of non-Alzheimer lobar atrophy. We review and illustrate two such
      syndromes--semantic dementia (SD) and progressive nonfluent aphasia (PA). SD
      involves loss of conceptual structure due to bilateral infratemporal atrophy. PA
      is a phonetic-syntactic disorder resulting from left perisylvian atrophy. Early
      research on Pick disease--originally defined as circumscribed cerebrocortical
      atrophy--highlighted left temporal lobe atrophy and aphasia. For this reason
      (among others), Pick disease or Pick complex is still a useful and convenient
      label for progressive aphasias and other clinical manifestations of non-AD lobar
      atrophy.

PMID- 12043418
TI  - [Swedish guidelines for prevention and treatment of pain in the newborn infant].
AB  - A Swedish national consensus statement concerning prevention and management of
      pain in the newborn infant has been prepared by members of the Swedish Paediatric
      Pain Society (Svensk Barnsmartforening, SBSF). The document is based on the
      Consensus Statement for the Prevention and Management of Pain in the Newborn
      Infant by Anand et al [1].

PMID- 12043416
TI  - [How was the referral sheet interpreted? Questionnaire on priority assessment of
      patients referred to orthopedic surgeons showed great differences between
      reviewers].
AB  - A questionnaire containing 15 simulated referrals for orthopedic specialist
      treatment was distributed to physicians in charge of determining priority. They
      were asked to consider each referral in a normal way and grade them in order of
      priority. The results overall showed great divergence; units with longer waiting
      lists assigned the patients lower priority than did units with short waiting
      lists. There is a pressing need for national guidelines in order to improve the
      referral sheet as an instrument of communication.

PMID- 12043419
TI  - [Pain relief in newborn infants with oral sucrose solution. More knowledge of
      neurophysiology is required for further application].

PMID- 12043421
TI  - [Pre-, pro-, per--productive prefix].

PMID- 12043420
TI  - [Alpha-1,3-galactosyltransferase-free pigs. Whether this is the solution of the
      great rejection problem in xenotransplantation remains to be seen].

PMID- 12043422
TI  - [Jean Baptiste Lully. The man who acquired monopoly of the French opera].

PMID- 12043423
TI  - [Marketing of researchers--lack of judgment or a new trend?].

PMID- 12043424
TI  - [Marketing of the LIFE trial anticipates evaluation of the drug].

PMID- 12043425
TI  - [Reduced levels of lipids and cerebrovascular disease--benefits and risks?].

PMID- 12043426
TI  - [Surgery is no longer an obvious routine in abdominal cancer].

PMID- 12043427
TI  - [Rectal palpation in appendicitis].

PMID- 12043428
TI  - The economics of schizophrenia care in Europe: the EPSILON study.

PMID- 12043429
TI  - The conduct of successful multi-site EU collaborative research: the EPSILON
      Study.

PMID- 12043430
TI  - The use of patient-level outcomes to inform treatment.
AB  - OBJECTIVE: The assessment of outcome for any purpose is not undertaken routinely
      in European mental health services. This paper discusses the merits of using
      outcome data to inform the planning of mental health care for individual
      patients, and provides practical advice to support the implementation of this new
      approach to working. METHOD: The use of outcomes in North America and Europe is
      briefly reviewed. A conceptual basis is proposed for routine outcome assessment-
      the ongoing measurement and use of outcome data to inform decisions about whether
      to continue, change or curtail treatment. A cognitive psychology model is
      developed which indicates that the routine use of outcomes will improve mental
      health care. Perceived problems with routine outcome assessment are discussed,
      and principles for implementation are identified. RESULTS: Outcomes are used
      mainly for generating local-level (rather than patient-level) data in North
      America, and rarely used in Europe. The use of outcome data routinely may
      facilitate reflective clinical practice, a model of decision-making which leads
      to a higher quality of clinical care than automated problem-solving. One issue
      relates to the use of standardised assessments designed for research purposes in
      clinical settings, and this is being addressed through the development of a new
      generation of outcome measures which are explicitly designed for clinical use.
      However, most clinicians remain unconvinced of the benefits of routine outcome
      assessment, and relevant research is currently underway across Europe which will
      address this concern. Scientific principles to maximise quality and pragmatic
      principles to maximise the chances of successful implementation are identified.
      CONCLUSIONS: The routine use of outcomes will become increasingly prominent in
      European mental health services. This provides clinicians with an opportunity to
      improve the quality of clinical care offered to patients.

PMID- 12043431
TI  - [A systemic review of the European Agency for the evaluation of medicinal
      products (EMEA) recommendations on the conduct of clinical trials in psychiatry].
AB  - OBJECTIVE: This article critically reviews the European Agency for the Evaluation
      of Medicinal Products (EMEA) recommendations on the conduct of clinical trials in
      psychiatry. The EMEA is a regulatory body which provides the institutions of the
      European Community with the best possible scientific advice on the quality,
      safety, and efficacy of medicinal products. METHOD: Systematic review of
      recommendations, guide-lines and official documents available in the EMEA web
      site. RESULTS: Out of nearly 400 documents, we identified 4 documents on the
      conduct of clinical trials in specific psychiatric disorders and 5 on the use of
      placebo or active comparator in evaluating a new drug's efficacy and on
      methodological issues in establishing difference and equivalence of effect. The
      EMEA recommends clinical trials to detect a difference between the compound under
      investigation and placebo, and to assess at least non-inferiority against an
      active comparator. A placebo arm is intended to validate the study. The EMEA
      supports the use of placebo only when there is no serious risk for the patient.
      In schizophrenia, depression and bipolar disorder the Agency suggests that a
      three-arm study is the design of choice, to demonstrate superiority against
      placebo and a similar balance against an active comparator. CONCLUSIONS: Despite
      the many effective therapeutic options available for the pharmacological
      management of psychiatric disorders, the EMEA regulatory process still relies on
      the demonstration of efficacy in absolute terms, against a placebo. We discuss
      this position and put at issue the possibility of developing a new generation of
      trials to demonstrate superiority of effect of new compounds over reference ones.

PMID- 12043432
TI  - [Causes and psychosocial consequences of schizophrenia: opinions of mental health
      personnel].
AB  - OBJECTIVE: Description of the opinions about causes and psychosocial consequences
      of schizophrenia in a sample of psychiatric professionals, recruited in 29
      Italian Mental Health Centres (MHC). DESIGN: Each professional was asked to read
      a case-vignette describing a patient who met the ICD-10 criteria for
      schizophrenia. Referring to case-vignette, he/she was asked to fill the
      Questionnaire on the Opinions about Mental Illness--Professionals' version (QO
      P). Professionals' opinions were explored in relation to: a) their socio
      demographic variables and professional background; b) geographic location of the
      MHC. SETTING: 29 MHC stratified by geographic area (Northern, Central, Southern
      Italy) and population density of their catchment areas (> 100,000 inhabitants;
      between 100,000 and 25,000 inhabitants; < 25,000 inhabitants) and randomly
      selected. RESULTS: Data on 465 professionals were collected. 75% of the sample
      identified in the vignette a case of schizophrenia, 22% of depression/anxiety
      disorder. Factors most frequently mentioned as causes of the detected disorder
      were heredity (68%), stress (61%), family difficulties (46%). More pessimistic
      opinions about psychosocial consequences of schizophrenia were found among nurses
      and among professionals of Southern Italy, among those with lower educational
      level, older age and among those working longer in psychiatry. No statistical
      difference in the opinions about psychosocial consequences of schizophrenia was
      found among staff who referred the case-vignette to schizophrenia and those who
      did not. CONCLUSIONS: The results of this study outline the need to: a) include
      issues such as disability and psychosocial consequences of mental disorders in
      the basic training of professionals; b) increase the number of professionals
      trained in evidence-based psychosocial interventions.

PMID- 12043433
TI  - [Disability in schizophrenia. Intrinsic factors and prediction of psychosocial
      outcome. An analysis of literature].
AB  - OBJECTIVE: Many different factors, both related to the individual and illness
      ("intrinsic" factors) and to the environment ("extrinsic" factors), contribute in
      different ways to the development of disability. Basing on data of literature,
      this review focuses the main "intrinsic" factors predicting disability in
      schizophrenia. METHOD: A systematic search on Mediline of all papers published
      during the period 1965-2001 was performed, using "schizophrenia", "outcome",
      "psychosocial outcome", "social disability" and "social adjustment" as key words.
      Only papers reporting specifically data about predictive factors and psychosocial
      outcome variables were considered; prospective follow-up studies were considered,
      but retrospective and cross-sectional studies were also taken into account when
      data deriving from prospective studies were inconsistent. RESULTS: Male sex
      predicts a higher disability among demographic factors; lower social and
      occupational adjustment are premorbid personality factors associated with higher
      disability; among factors related to illness, younger age at onset of illness,
      "nuclear", "non paranoid" and in particular "deficit" forms of schizophrenia seem
      to predict more disability. The latter seems to be predicted also by higher
      levels of negative symptoms and neuropsychological deficits; the role of
      depressive symptoms seems to be less supported by follow-up data; a continuous
      course of the illness predicts more disability, although some evidences show a
      progressive reduction of disability, at least in the long term. CONCLUSIONS:
      Disability shows a largely autonomous course respect to symptoms and has to be
      considered an independent parameter of outcome. Few intrinsic factors show a
      predictive role also in the long term.

PMID- 12043434
TI  - The iceberg tip and the rest. Mental health care for people with schizophrenia in
      five European centres.

PMID- 12043435
TI  - [Suspicious circumstances on discovery of the cadaver].
AB  - The authors report on three autopsy cases in which the findings at the death
      scene gave rise to the suspect of non-natural, in two cases even violent causes
      of death. The medico-legal and criminalistic investigations led to surprising
      results: Death was due to acute intoxication with narcotics, supposed delirium
      tremens and a suicide attempt in the presence of bronchopneumonia. External force
      was ruled out in all three fatalities by cooperative work of police investigators
      and forensic medicine.

PMID- 12043436
TI  - [Modern variant of hanging: use of a time-programmed winch].
AB  - Hanging is one of the most frequent types of suicide. Descriptions of unusual
      ligatures can be read about again and again. The paper reports the suicide of a
      41-year-old electrician, who, using an electric winch, hung himself in nearly
      free suspension. The winch that was secured to the timberwork of the attic had
      been programmed by an electric time clock, the toggle switch of the remote
      control was fixed in the on-position using adhesive tape. The man had handcuffed
      his hands behind his back against any attempts to save himself. The noose was
      partly cushioned with a bike tube with the obvious aim of reducing the pain. Due
      to the state, in which he was found and the results of the post-mortem
      examination, a third party responsibility was excluded. The case shows that not
      only certain types of knots and nooses can be associated with various
      occupational groups, but the choice of a special strangulation device can
      possibly also come from the occupational sphere. As a modern variation of
      hanging, the presented casuistry can partly complete the familiar documentation
      of historical cases with the use of block and tackle and similar constructions.

PMID- 12043437
TI  - [Killing a wolf--an unusual case of forensic veterinary pathology].
AB  - During a hunt in Western Pomerania in January 1999 a wolf, injured at the left
      hind leg, was killed by a shot in the chest region. It was a 2-year-old male that
      probably came to Germany from Poland by crossing the Oder River. The hunter was
      reported to the police afterwards, because there were doubts as to the legality
      of the lethal shot. The hunter pleaded relief by reason of section 22 a German
      Hunting Law (prevention of avoidable pain or suffering of wild animals). After
      the shooting there was a number of wrong expert statements by a veterinarian and
      two zoologists concerning the age of the injury on the left hind leg and the
      direction of the shot to the chest region, which were corrected by subsequent
      medico-legal examinations performed on the order of the prosecution.

PMID- 12043438
TI  - [Suicide with exit bags: circumstances and special problem situations in assisted
      suicide].
AB  - So-called exit bags are voluminous, transparent plastic bags, each with a collar
      to go round the neck, and a Velcro fastening. In conjunction with the consumption
      of sleeping pills, the bags are recommended as an aid to commit suicide by
      organizations in favour of "humane death". It is reported on four such suicides
      by elderly people between 79 and 87 years of age. In two of these cases, there
      was assistance in committing suicide, one corresponding to a suicide protocol
      from the Swiss organization for euthanasia, EXIT. In two cases, detailed
      instructions for committing suicide were found. The morphological findings were
      not very specific in any of the cases. If the plastic bags are removed by a third
      party, this type of suicide may remain undetected even after performance of an
      autopsy. Exit bags tend to be used by older people with either real or feared
      life-threatening illnesses, in suicides which have usually been planned for some
      time. From the criminological point of view, the possible active participation of
      other persons in pulling the covering over the head can often not be proved.
      Assisting a suicide, in the sense of giving instructions on how to accomplish it,
      is not punishable in German law.

PMID- 12043439
TI  - [Cause of death in heroin users with low blood morphine concentration].
AB  - The blood morphine concentrations in cases of heroin-associated fatalities can
      vary considerably. Currently, a free-morphine concentration of > or = 100 ng/ml
      in blood is generally considered as potentially fatal. Moreover, it is a common
      observation that fatal cases of heroin-intoxication with blood morphine
      concentrations lower than 100 ng/ml occur. This poses the question of how the
      fatal cases with low blood morphine concentrations can be explained. In the study
      described here, 62 cases of morphine only intoxications were examined. The fatal
      cases were divided into two groups according to the free morphine concentrations
      measured in the blood of the heart (group I: free morphine concentration < 100
      ng/ml, n = 21 cases; group II: free morphine concentration > or = 100 ng/ml, n =
      41 cases). The two groups were compared as to circumstances of death, as well as
      to autopsy findings and histopathologic alterations. Overall, infections of the
      respiratory tract occurred significantly more often in group I (lower morphine
      concentrations) than in group II. In a second step, the group I cases were
      analyzed individually to get detailed information on the cause of death. In 19 of
      the 21 cases the authors could find a plausible explanation for death in
      combination with low free morphine concentrations in the blood.

PMID- 12043440
TI  - [Continued physical capacity after head gunshot injury].
AB  - The human brain shows a very high density of functionally important structures.
      Even small lesions may therefore cause clinical symptoms. Penetrating gunshots to
      the head are presumed to cause immediate incapacitation by subsequent disturbance
      of cerebral functions. The authors discuss anatomical and functional principles
      of the terms action, capacity to act and incapacitation and report two
      illustrative cases with lack of incapacitation following gunshots to the head.

PMID- 12043441
TI  - [Fatal outcome of poisoning with the benzodiazepines flunitrazepam and diazepam].
AB  - On a wintry day a 29-year-old woman was found dead beside her car showing head
      injuries and signs of hypothermia. Several empty packets of sedative and hypnotic
      drugs were lying inside the car. Toxicological analysis revealed the presence of
      flunitrazepam (heart blood of the left and right chamber 0.033 mg/L each),
      norflunitrazepam (left heart blood 0.029 mg/L, right heart blood 0.027 mg/L), 7
      amino-flunitrazepam (left heart blood 0.090 mg/L, right heart blood 0.104 mg/L),
      diazepam (left heart blood 0.395 mg/L, right heart blood 0.386 mg/L), nordazepam
      (left heart blood 0.112 mg/L, right heart blood 0.115 mg/L) and temazepam (left
      heart blood 0.034 mg/L, right heart blood 0.033 mg/L). Neither alcohol nor other
      drugs were found. It was concluded that benzodiazepine intake led to a
      disturbance of consciousness. Whether the woman died in this situation due to the
      icy temperature as a result of hypothermia or whether she died or would have died
      solely due to benzodiazepine overdosage could not be clarified.

PMID- 12043442
TI  - [Vulvovaginal complaints, dyspareunia and oral mucosa abnormalities: erosive
      lichen planus].
AB  - Three women, aged 46, 48 and 73 years respectively, suffered from erosive genital
      lichen planus. Vulvar irritation, dyspareunia and vaginal discharge are the
      prominent signs of this disease. Lichen planus is an inflammatory dermatosis,
      which can involve skin and oral and genital mucosa. Diagnosis and treatment are
      difficult. Prolonged local application of a corticosteroid cream, e.g.
      clobetasol, is usually warranted. Narrowing of the vagina and painful mucosal
      lesions often prevent sexual intercourse. The combination of oral and genital
      complaints can help in the diagnosis of lichen planus. Strict follow-up is
      necessary because of the possible malignant degeneration of the disease.

PMID- 12043443
TI  - [Gastrointestinal surgery and gastroenterology. XV. Polycystic liver disease].
AB  - Polycystic liver disease is a congenital disorder with an autosomal dominant
      pattern of inheritance. There are two variants. In one, liver cysts occur as an
      extra-renal phenomenon in autosomal dominant polycystic kidney disease. In the
      other, the disease is not associated with renal pathology. The cysts have to
      reach a certain diameter before becoming clinically manifest and therefore are
      generally only detected many years after birth. Polycystic liver disease causes
      symptoms in 20% of the patients. These symptoms are the consequence of the weight
      and size of the liver or of complications such as abscess formation, obstructive
      jaundice or the Budd-Chiari syndrome. Most symptoms can be treated at least
      temporarily by fenestration of the larger cysts and resection of parts of the
      liver, which are affected by large groups of small cysts. A permanent cure of the
      disease is only obtained by liver transplantation.

PMID- 12043444
TI  - [Cardiovascular effects of hyperthyroidism and their treatment].
AB  - The most striking clinical effects of hyperthyroidism are on the heart. These
      effects concern both heart rate and function. The increased contractility is
      mainly based on the indirect inotropic effect of peripheral vasodilation as a
      consequence of hyperthyroidism. Although contractility at rest is enhanced in
      hyperthyroidism, cardiac reserve is decreased due to diminished chronotropic,
      inotropic and vasodilatory reserve. In hyperthyroid patients, the clinical
      impression is often that of a hyperadrenergic circulation. However, the
      sensitivity of the heart for catecholamines is not increased. The diminution of
      palpitations by beta-adrenergic blockers in hyperthyroid patients is due to both
      a decrease in heart rate and atrial extrasystoles, and is not the consequence of
      a normalisation of cardiac contractility. Heart failure is almost exclusively
      found in patients with pre-existing cardiac disease. In the case of serious heart
      failure a rapid reduction of circulating thyroid hormone by means of
      thyreostatics is important as well. There is no consensus as to whether patients
      with thyrotoxic atrial fibrillation should be treated with oral anticoagulants.
      However, most experts recommend oral anticoagulants for elderly patients (> 60
      years) or patients with additional risk factors for embolism.

PMID- 12043445
TI  - [Diagnostic image (88). An infant with projectile vomiting].
AB  - A one-month-old infant was admitted with projectile vomiting due to a
      hypertrophic pyloric stenosis. A pyloromyotomy was successfully performed.

PMID- 12043446
TI  - [Drug-related problems in an emergency department in the center of Amsterdam,
      June-November 2000].
AB  - OBJECTIVE: To gain insight into the nature and magnitude of drug-related problems
      in the emergency department (ED) of a hospital (Onze Lieve Vrouwe Gasthuis) in
      Amsterdam, the Netherlands. DESIGN: Prospective, observational. METHOD: During
      the period from June through to November 2000, the following data were recorded
      for all patients visiting the ED with drug-related problems: age, sex,
      nationality, form of presentation, presenting complaint, drugs used, diagnostics
      performed, treatment in the ED and clinical course leaving the ED. RESULTS:
      During the study period, 214 (1%) patients were seen with drug-related problems.
      The largest group consisted mainly of young, foreign occasional users of soft
      drugs (117 patients, 55%). Their complaints were aspecific and harmless. The need
      for additional diagnostics was limited, with no additional diagnostic tests being
      carried out in 178 patients (83%). Treatment consisted of reassurance (50
      patients, 23%), observation (123 patients, 58%) and medication (85 patients,
      40%). Nineteen patients (9%) needed additional treatment (suturing, plastering,
      etc.). Ten patients (5%) were admitted to the hospital. Reasons for admission
      were psychotic episodes, prolonged unconsciousness or respiratory problems.
      CONCLUSION: The magnitude of the drug problem in an emergency department in the
      centre of Amsterdam and the use of medical resources were limited. The nature of
      the problem consisted mainly of mild symptoms following the use of soft drugs,
      usually by young, foreign occasional users.

PMID- 12043447
TI  - [Metabolic disregulation after starting feeding: "refeeding" syndrome: the
      central role of phosphate].
AB  - A 47-year-old man was admitted due to serious weight loss after several months in
      which he had not eaten and had drunk almost solely beer. Shortly after the start
      of enteral tube feeding, the patient developed serious heart failure. This was
      associated with severely disrupted electrolyte levels and in particular
      hypophosphataemia and hypomagnesaemia. This condition is termed refeeding
      syndrome. The circulating volume increases due to the hyperinsulinaemia which
      occurs during the feeding phase. Furthermore a shortage of ATP occurs and the
      heart may fail. In efforts to establish feeding, a weight increase of not more
      than 1 kg per week should be attempted; if the weight increases by more than
      this, then fluid retention is the probable cause.

PMID- 12043448
TI  - [Kernicterus in a full-term male infant a few days old].
AB  - A male baby born at term via an uncomplicated vaginal delivery was presented on
      the fourth day of life with jaundice, accompanied by neurological symptoms
      related to kernicterus. Despite extensive investigations, a clear cause for his
      hyperbilirubinaemia could not be found. After 10 days of intensive care he was
      left with deafness and a severe extrapyramidal motor disturbance. Recently
      revised practice guidelines suggest a less aggressive approach for the treatment
      of jaundice with phototherapy or exchange transfusion in newborns. However, in
      the presence of factors for kernicterus, early and, if necessary, frequent
      measurement of the serum bilirubin concentration remains important to prevent
      serious and life-long complications.

PMID- 12043449
TI  - [Airway fire, a serious complication of laser surgery of the larynx].

PMID- 12043451
TI  - [Hypoglycemia due to oral hypoglycemic agents: chance of adverse effects after
      restoration of blood glucose level].

PMID- 12043452
TI  - [Anthrax due to deliberate infection].

PMID- 12043453
TI  - [Non-scrotal testes: first line of therapy].

PMID- 12043454
TI  - [Adverse effects of passive smoking on the (unborn) child].

PMID- 12043455
TI  - Determination of amlodipine in pharmaceutical formulations by differential-pulse
      voltammetry with a glassy carbon electrode.
AB  - A differential-pulse voltammetric method was developed for the determination of
      amlodipine based on the oxidation of the dihydropyridine group on the surface of
      glassy carbon electrode under stationary and rotating conditions. The experiments
      were conducted in a supporting electrolyte consisting of 0.2 M KCl, 0.1 M
      phosphate buffer, and 10% (v/v) methanol during investigation of initial
      potential and pH effects. No adsorption effect was observed on using an initial
      potential of 0 mV and the supporting electrolyte solution at pH 5.5 under both
      stationary and rotating conditions. The factor affecting the voltammetric current
      was diffusional in the range of 200-1000 rpm for rotating, and 2-40 mV s-1 for
      stationary conditions up to a concentration of 0.04 mg mL-1 amlodipine. The limit
      of detection (LOD) and the limit of quantitative (LOQ) for the rotating and
      stationary techniques were found to be 0.004 and 0.0072 mg mL-1 (for S/N = 3.3)
      and LOQ 0.012 and 0.022 mg mL-1 (for S/N = 10), respectively. The proposed method
      was applied to the tablets containing amlodipine and according to the statistical
      evaluations acceptable results were obtained at the 95% probability level.

PMID- 12043456
TI  - Establishment and characterization of new murine breast cancer cell lines.
AB  - The establishment of two new breast cancer cell lines, MXT+ and MXT-, derived
      from the murine breast cancer models MXT-M-3,2 MC (hormone-sensitive) and MXT-M
      3,2 (ovex) MC (hormone-insensitive), is described. Characterization of the cell
      lines was performed by investigation of morphology, steroid hormone receptor
      state, growth kinetics, and drug response as well as by cytogenetic analysis.
      MXT+ contains estrogen receptors (ER; 6.9 fmol/mg protein) as well as
      progesterone receptors (PgR; 9.2 fmol/mg protein) and therefore is inhibited by
      tamoxifen (Tam). MXT- proved to be ER- but PgR+ (23.4 fmol/mg protein) and, as
      expected, resistant against Tam. The sensitivity of MXT+ and MXT- against a
      pattern of therapeutically established anti-breast cancer drugs (cDDP, cisplatin;
      JM-8, carboplatin; DX, adriamycin; 5-FU, 5-fluorouracil; MTX, methotrexate; VLB
      vinblastine) was studied by use of a computerized, kinetic chemosensitivity assay
      based on quantification of biomass by staining cells with crystal violet. For
      each compound the inhibition profile reflecting cytostatic, transient cytotoxic,
      or cytocidal drug effects as well as development of resistance was evaluated. The
      following order of activity was found: MTX > VLB > or = DX > cDDP > or = 5-FU >
      JM-8. The test data of 5-FU, VLB, cDDP, and Tam on MXT+ as well as on MXT- were
      compared with those from studies on ER+ and ER- human breast cancer cell lines
      (MCF-7, ZR-75-1, T-47-D, and MDA-MB-231, respectively). They revealed comparable
      inhibition profiles and sensitivities of human and murine breast cancer cell
      lines, an indication that the results achieved in combined in vitro-/in vivo
      tests by use of the murine test models MXT+, MXT-, MXT-M-3,2 MC, and MXT-M
      3,2(ovex) MC are relevant for therapy in humans.

PMID- 12043457
TI  - Synthesis and antihypertensive activities of new 1,4-dihydropyridine containing
      nitroimidazolyl substituent with a nitrooxy group at the 3-ester position.
AB  - New analogues of nifedipine, in which the ortho nitrophenyl group of position 4
      is replaced by 1-methyl-4-nitro-5-imidazolyl or 1-methyl-5-imidazolyl with a
      nitrooxy group at the 3-ester position were synthesized, and the antihypertensive
      activity of the compounds was examined by the tail-cuff method and compared with
      TNG and nifedipine. Compounds 11g, 11i-11m, 11o, 11r, and 11v showed activity
      similar to nifedipine and TNG.

PMID- 12043458
TI  - Photochemical study of hexahydroquinoline derivatives--a new group of calcium
      antagonists.
AB  - The photochemical stability of 2,6,6-trimethyl-3-carbmethoxy-4-phenyl-5-oxo
      1,4,5,6,7,8-hexahydroquinoline (HHQ) derivatives with different substituents on
      the phenyl ring (-Cl, -NO2, -CF3, -CH3, -OCH3) has been studied. The process of
      photodegradation was studied by UV spectrophotometry. The rate of
      photodegradation was found to depend on the type and position of the substituent
      in the phenyl ring. The compounds most susceptible to the damaging effect of
      light proved to be those containing the nitro group, in particular with the
      substituent in the ortho position of the aromatic ring. Derivatives with alkyl (
      CH3) and halo-alkyl (-CF3) substituents showed the greatest photochemical
      stability. The compounds with substituents in the ortho position were found to be
      much less photostable than the meta isomers. The quantum yield values obtained
      ranged from 10(-4) to 10(-3), indicating the occurrence of secondary
      photochemical processes initiated by the primary products of decomposition.

PMID- 12043459
TI  - Synthesis and biological evaluation of 4-(4-(alkyl- and
      phenylaminocarbonyl)benzoyl)benzoic acid derivatives as non-steroidal inhibitors
      of steroid 5 alpha-reductase isozymes 1 and 2.
AB  - The synthesis and biological evaluation of 4-(4-(alkyl- and
      phenylaminocarbonyl)benzoyl)benzoic acids (4a-4d) as non-steroidal inhibitors of
      steroid 5 alpha-reductase are described. The compounds were tested in vitro for
      inhibitory activity toward rat and human 5 alpha-reductase isozymes 1 and 2 at a
      concentration of 10 microM. The most active inhibitor for the human type 2
      isozyme was 4-(4-(phenylaminocarbonyl)benzoyl)benzoic acid, compound 4c (IC50 =
      0.82 microM).

PMID- 12043460
TI  - Hydrogels formed by crosslinked poly(vinyl alcohol) as sustained drug delivery
      systems.
AB  - Poly(vinyl alcohol) was crosslinked with ethylene glycol diglycidyl ether to
      obtain hydrogel-forming polymers. The polymers were also substituted with oleoyl
      chloride, providing hydrogels with weak solubility. These new polymeric materials
      were evaluated for the formulation of sustained drug delivery systems. Vancomycin
      hydrochloride was used as a peptidic model drug whose sustained release should
      minimize its inactivation in the upper part of the gastrointestinal tract. Spray
      dried mixtures of the drug and the polymer [at 1:4 and 1:8 (w:w) ratios] were
      prepared and the release of the drugs from the mixtures was evaluated in vitro at
      pH 2.0, 5.5, 7.4, and 8.0. The results indicated that the crosslinked polymers
      slowed down the release of the drugs with respect to the pure drug at each pH.
      The degree of crosslinking of ethylene glycol diglycidyl ether and the extent of
      substitution with oleoyl chloride were found to influence drug release.

PMID- 12043461
TI  - Synthesis and antimicrobial activity of hydroxyalkyl- and hydroxyacyl-phenols and
      their benzyl ethers.
AB  - New phenolic compounds with hydrophilic side chains were prepared from 4
      benzyloxybenzaldehyde and alkenyl magnesium bromides, followed by Sharpless
      dihydroxylation and hydrogenolytic removal of the benzyl group. The resulting
      compounds were tested in an agar diffusion assay against gram positive bacteria,
      gram negative bacteria, and against the fungi Candida glabrata and Aspergillus
      niger.

PMID- 12043462
TI  - Preparation and antibacterial activity of 3-methyl-1-p-substituted phenylpyrazole
      5-thiol.
AB  - 3-Methyl-1-phenylpyrazole-5-thiol (3a) and its p-nitro- (5) and p-fluorophenyl
      (8) derivatives were prepared as potential antimicrobial agents in relatively
      good yields. Compounds 3a and 8 showed good antibacterial activities against
      MRSA, S. aureus, S. epidermidis, E. faecalis, E. faecium, and S. pyogenes.
      Moreover, compound 3a also showed a synergistic effect with some aminoglycosides.

PMID- 12043463
TI  - [Postoperative pain in laparoscopic surgery].
AB  - The occurrence of post-operative pain, although less severe and frequent than in
      open surgery, may affect length of hospital stay and early return to normal
      activity in some patients operated on with laparoscopic surgery. Although several
      pathogenetic factors have been indicated in the literature, the mechanism
      responsible for post-operative pain after laparoscopy; still remains unclear. In
      this study the Authors evaluated post-operative pain in 90 patients submitted to
      laparoscopic cholecystectomy and correlated it to the length of operation,
      endoabdominal CO2 pressure maintained during surgery, and use of local anesthesia
      instilled din the liver bed and in the sites of introduction of trocars.
      Measuring post-operative pain by means of a modified Scott-Huskisson Visual
      Analogue Scale, no difference in the severity of the pain was noted in the two
      subgroups of patients with a length of operation inferior or superior to 60
      minutes, respectively. Conversely, a statistical significant difference (p = 0.04
      and p = 0.049 according to Fisher exact test and Pearson test, respectively) was
      observed evaluating the use of local anesthesia and the level of CO2
      endoabdominal pressure, with less pain in patients whose pressure was maintained
      under 10 mmHg and in patients treated with instillation of local anesthetic drugs
      in the liver bed and in the sites of introduction of trocars.

PMID- 12043464
TI  - [Damage control surgery: the technique].
AB  - Abdominal packing and planned reoperation is a lifesaving technique for temporary
      control of haemorrhage in severely injured patients. Morbidity and mortality,
      however, remain significant. The purpose of this study is to evaluate all
      surgical technique and our results during 31 years of trauma surgery. In the last
      12 years the Authors have performed 11 packing. They stressed fully "damage
      control technique" in trauma surgery in the last four years. Overall mortality
      was 45.5%.

PMID- 12043465
TI  - [Lipohyperplasia of the ileocecal valve: unusual cause of severe digestive
      surgery].
AB  - The lipohyperplasia of the ileocaecal valve is a condition of rare clinical
      observation mainly characterized by an abnormal accumulation of adipose tissue
      along the submucosal layer of the ileocaecal valve. This pathology presents an
      unspecific symptomatology that can make difficult the differential diagnosis with
      a local neoplastic process. Sometimes this pathology can be the cause of
      gastrointestinal bleeding of unknown origin. The Authors report a case of their
      observation that requested an emergency surgical operation for the massive
      digestive haemorrage at presentation. The definitive diagnosis could have been
      precised only after histological exam.

PMID- 12043466
TI  - [Is blood transfusion a risk factor in colorectal surgery for cancer?].
AB  - Personal experience in the treatment of 93 cases of cancer of the large bowel and
      rectal localization is reported 32 patients (A group) received blood
      transfusions, 61 patients (B group) hadn't any transfusions or autotransfusions.
      Postoperative morbidity was 34.37% in A group and 14.75% in B group. The Authors
      stress the basic importance of autotransfusions as well in patients surgically
      treated for colorectal cancer.

PMID- 12043467
TI  - [Esophageal atresia and tracheoesophageal fistula: personal contribution].
AB  - From January 1988 to December 1999, 21 new born babies, 13 boys and 8 girls, with
      esophageal atresia (EA) and tracheosophageal fistula (TEF) were treated at
      Division of Pediatric Surgery in Foggia (Italy). At birth their weight ranged
      from 1.600 to 3.000 g, the gestional age ranged from 36 to 41 weeks. Five (23%)
      of them were premature, seven (58%) SGA, seventeen (80%) associated congenital
      anomalies. Complete surgical correction was performed in all patients. In three
      AE cases with wide-gap an azygos vein flap was used to strengthen the anastomosis
      under excessive tension. The pathogenetic factors involved in these complications
      such as leak, stricture (stenosis), recurrent TEF and gastro-esophageal reflux
      are (are taken into account) and analysed. No baby died owing to anastomatic
      complication. Survival rate was 100% in Montreal I and 83% in Montreal II. A new
      born baby died but his death was due to major associated conenital anomalies and
      not to surgical complications. The Authors believe that the azygos vein flap is a
      useful technique in the treatment of esophageal atresia wide-gap.

PMID- 12043468
TI  - [Emergency treatment and diagnosis of appendix mucocele].
AB  - The Authors report a case of appendicular mucocele admitted in an emergency
      setting in the Emergency Department (DEA II). The patient, 78 y-old man, went to
      attention complaining diffuse abdominal pain: physical examination revealed mild
      tenderness and right lower quadrant pain to palpation. Rx plain and CT scan
      demonstrated a right iliac fossa cystic lesion with mural calcification, adherent
      to the caecum. On basis of imaging, clinical and laboratory findings the patient
      underwent surgery postoperative diagnosis was mucocele of the appendix. The aim
      of this report is to discuss the role of imaging and clinical approach in
      treatment of appendicular mucocele, which is known to be so aspecific in
      presentation, especially when it occurs in an emergency setting.

PMID- 12043469
TI  - [The general surgeon facing acute abdomen caused of gynecologic cause: diagnostic
      and therapeutic considerations on 2 cases].
AB  - The general surgeon has sometimes to face problems arising from an acute abdomen
      due to gynecologic causes. Such conditions are mainly found in women in
      reproductive age; the most frequent pathologies are due to complications of
      ovarian cysts, perlvic inflammatory disease and extrauterine pregnancy. Some
      short clinical commentaries are herein presented on two cases of gynecologic
      acute abdomen: the first case reported is related to an intraperitoneal rupture
      of a large uterine sarcoma and the second an ovarian neoplasm associated with a
      diffuse peritonitis from perforation of tubo-ovarian abscess.

PMID- 12043470
TI  - [Synchronous lung cancer; clinical case of triple lung carcinoma].
AB  - The case of a 57-year-old man with three synchronous malignancies of the lung
      (adenocarcinoma, small cell carcinoma, squamous carcinoma in situ) is presented.
      This is one of the few cases reported in the literature with three different
      histologic types in the same pulmonary lobe.

PMID- 12043471
TI  - [Pre- and postoperative external biliary drainage in patients with obstructive
      jaundice caused by neoplasm of the pancreatic head].
AB  - The external biliary drainage in severe jaundice secondary to pancreatic
      carcinoma acts differently in pre, intra, and postoperative period. In the
      preoperative period the drainage enables to lower the direct bilirubinemia and
      the intrahepatic biliary stasis and consequently the complications linked to the
      impaired hepatic and renal function. During the operation the catheter acts as a
      guide in performing the biliodigestive anastomosis. In the postoperative period
      the external drainage of most of daily biliary secretion protects the
      biliodigestive anastomosis during the postoperative paralytic ileus, and prevents
      the fistula development along the pancreatic jejunal anastomosis.

PMID- 12043472
TI  - [Use of ileostomy and colostomy as temporal derivation in colorectal surgery].
AB  - A retrospective study on 41 patients with primary stoma creation after low
      anterior resection of the rectum was made. Among the 41 patients 24 had a loop
      colostomy (Group A) and 17 had a loop ileostomy (Group B). The two groups were
      well matched for each of the data analysed and there was no significant
      difference in the rate of complications related to stomas creation and closure.
      In this study the Authors suggest that loop ileostomy is the best procedure to
      electively defunctionate colorectal anastomoses.

PMID- 12043473
TI  - [Radiologic features of villous adenoma of the large intestine].

PMID- 12043474
TI  - [Endoscopic prosthesis in colonic malignant pathology].
AB  - The utilization of stents in neoplastic colon pathology finds a correct location
      in the therapeutic panorama. Authors report the use of enteric stents as
      definitive treatment in acute intestinal occlusion with inoperable malignant
      neoplasia as well as palliative treatment in intestinal occlusion with non
      surgically resectable neoplasia.

PMID- 12043475
TI  - [Fear of adverse effects threatens the vaccination programs. Risk of re-emerging
      of "old-fashioned" childhood diseases with the reduced vaccination coverage].

PMID- 12043476
TI  - [Is fasting after gastrointestinal surgery necessary? Meta-analysis of early
      enteral nutrition versus traditional nutritional therapy].

PMID- 12043477
TI  - [Results from the LIFE study: promising effects of new hypertensive agents].

PMID- 12043478
TI  - [High blood lipids levels--attitudes and management. Different strategies among
      physicians create uncertainty concerning the therapeutic recommendations].
AB  - In comparing occupational health physicians, GP's and internists in 1990, the
      former screened their patients for cholesterol, unlike the others, and were more
      rigorous in their treatment of hyperlipidemia. In 1995 all groups had intensified
      secondary preventive measures. GP's had decreased primary preventive efforts. In
      the parallel population follow-up study, interest in lipids had decreased,
      perhaps echoing the lack of preventive measures in primary health care and the
      differences among the groups of doctors. Swedish doctors instituted treatment at
      higher cholesterol levels than did their Italian colleagues. GP's varied markedly
      in their strategies for treatment of moderately high cholesterol in patients who
      in addition had other risk-factors. There is a risk that varied treatment
      strategies and attitudes among doctors make it difficult for patients to adhere
      to prescribed treatment.

PMID- 12043479
TI  - [Few patients with coronary diseases are receiving lipid-lowering therapy].

PMID- 12043480
TI  - [Mucopolysaccharidoses. New therapeutic possibilities increase the need of early
      diagnosis].
AB  - The mucopolysaccharide (MPS) diseases are a group of inherited, progressive,
      lysosomal disorders due to deficiencies in various enzymes involved in the
      lysosomal degradation of cellular glycosaminoglycans (GAG). The six MPS-diseases
      share clinical features, but each has unique characteristics as well. There is a
      wide variation in clinical symptomatology even within the same enzyme deficiency.
      The MPS-diseases are very rare, with only 1-2 affected children born yearly in
      Sweden (100.000 births). Prenatal diagnosis is available for each condition. Bone
      marrow transplantation has been utilized to replace the enzyme deficiency in
      Hurler's syndrome (MPS I) and Maroteaux-Lamy's syndrome (MPS VI) for the past two
      decades. When performed before 18-24 months of age in Hurler's syndrome, mental
      development can be preserved. In this overview we present Swedish incidence and
      prevalence figures for the different forms of mucopolysaccharidosis, typical
      symptoms at onset, complications, diagnostic methods and a summary of the present
      status of research, and finally options for future treatment.

PMID- 12043481
TI  - [Cognitive outcome of childhood depression using cognitive behavior therapy].
AB  - Depressive symptoms and disorders are common among children and increase in
      prevalence, in particular among adolescent girls. The stability of these mental
      health problems, the risk of recurrence and their association with suicidality
      are important issues that underline the need for effective treatment methods to
      be used in child psychiatric services. This review focuses on the effects of
      psychological and drug treatments for depressed and suicidal children and
      adolescents, evaluated in empirical research during recent decades. It is
      concluded that cognitive-behavioural approaches have shown positive outcomes in
      most studies conducted with school samples, as well as in clinic samples of
      children and adolescents. By contrast, in only one placebo-controlled study
      fluoxetine (SSRI) has shown to be effective in the treatment of depressive
      disorders in these age groups. Preventive intervention programmes administered in
      school settings have not been successful and limited research, but also with
      negative outcomes exists, on clinic-based interventions for suicidal adolescents.
      This area needs to be further addressed in future research.

PMID- 12043482
TI  - [Low intellectual level--normal, but not without problems].

PMID- 12043483
TI  - [Pain relief in induced abortion--considerable differences between hospital
      departments].
AB  - Women undergoing medical abortions require different types of pain relief, severe
      pain being a problem. This study compared the pain relief required during a
      medical abortion at the Departments of Gynecology in Kalmar and Karlskrona. The
      case notes of 100 women at each department were examined. Considerable
      differences between the two departments were found. In Kalmar women were mainly
      given paracetamol and dextropropoxyphene at the start of the procedure, while in
      Karlskrona women were usually given suppository diclofenac. In Kalmar 42 per cent
      of the women needed some form of opiate during the abortion, while in Karlskrona
      only 8 per cent required opiates.

PMID- 12043484
TI  - [Quality of health care is threatened by physicians' insecurity in connection
      with decision making and by high costs].

PMID- 12043485
TI  - [Interactive health communication can improve the quality of health care].

PMID- 12043486
TI  - [Increased demands on the Swedish family practitioners' organizations in future.
      The DLF's delegate should organize establishment of a Family Practitioners'
      Committee].

PMID- 12043487
TI  - [Primary prevention of osteoporosis--a pharmacological dilemma?].

PMID- 12043488
TI  - [A reply concerning communication diseases: The idea of a competence center is
      fine but only if such a center is a real one!].

PMID- 12043489
TI  - [Answer of Lars Jacobsson and Marie Asberg to their critics: Why a compulsory
      training when psychotherapeutic education of future psychotherapists is wanted by
      everybody?].

PMID- 12043490
TI  - [Opportunistic screening for diabetes in primary health care. Life style changes
      can prevent diabetes mellitus among individuals at risk].

PMID- 12043491
TI  - [Somatization--a reply to elucidate the concepts].

PMID- 12043492
TI  - [Working place codes--a dreary decision].

PMID- 12043493
TI  - [Discount drugs--for the "politically correct" only?].

PMID- 12043494
TI  - [Uncritically about alternative medicine].

PMID- 12043495
TI  - [The essentials of the debate about the Expressen and publishing of names are
      missing].

PMID- 12043496
TI  - [A comment to Helle Kieler's summary of a study on ultrasound and left
      handedness].

PMID- 12043497
TI  - NHS fraud. Here's the catch.

PMID- 12043498
TI  - Open space. Ties that bind.

PMID- 12043499
TI  - Health systems. And ne'er the twain shall meet.
AB  - The differences between the English and Scottish health systems are becoming
      increasingly wide. The star-grading system in England has led to a winners and
      losers model, whereas Scotland has gone for a more collective approach. England
      has emphasised partnership with the private sector, Scotland with the voluntary
      sector and councils. Both systems will rely increasingly on staff involvement.

PMID- 12043500
TI  - [Sentinel node and breast cancer: fashion or surgical revolution?].

PMID- 12043501
TI  - [True and false hyperprolactinemia: how to discriminate one from the other in
      infertility management?].
AB  - Serum prolactin measurement is usually performed in infertility evaluation, even
      if there's no specific clinical presentation of hyperprolactinemia. High levels
      of prolactin are noted in 20 to 30% of menstrual abnormalities and in about 10%
      of regular menses. It is of importance to determine whether hyperprolactinemia is
      related to pituitary adenoma, drug administration, general diseases, or
      circulating large forms of prolactin, in order to avoid heavy, expensive, time
      consuming and unnecessary clinical investigations or therapeutic actions. We must
      first to confirm the biological diagnosis of hyperprolactinemia with few repeated
      plasmatic measurements, and, later, if necessary use TRH-metoclopramide test
      and/or pituitary magnetic resonance imaging.

PMID- 12043502
TI  - [Mechanisms of the stagnation of dilatation in the active phase of labor].
AB  - OBJECTIVE: Our study was designed to explain determinants of nonprogressive labor
      in nulliparous patients. STUDY DESIGN: One hundred consecutive nulliparous
      patients have got a cesarean section for active-phase arrest of labor after two
      hours of active management. Intrauterine pressure was monitored for all of them
      and a X-ray pelvimetry was done after surgery. RESULTS: Eighty-three percent of
      patients showed X-ray data considered as normal; hypotonic labor was found in 50%
      of cases and occiput posterior position in 60%. CONCLUSIONS: Our results suggest
      that occiput position and functional dystocia are more common in case of
      nonprogressive labor than abnormal measurements of the obstetrical pelvis.

PMID- 12043503
TI  - [Open laparoscopy: analysis of complications due to first trocar insertion].
AB  - OBJECTIVE: To evaluate the complications of open laparoscopy during the set-up of
      laparoscopy in gynecologic surgery. DESIGN: Retrospective study performed between
      February 1994 and January 2001 in a University Centre. PATIENTS AND METHODS:
      1,562 patients underwent open laparoscopies. Procedures were performed by 8
      gynaecological surgeons. Peri- and postoperative complications were assessed and
      analysed. RESULTS: Major injuries concerned gastrointestinal tract: 2
      perforations with immediate diagnosis and one postoperative occlusion treated by
      delayed laparotomy (0.19%). No death occurred. No vascular injuries and no
      bladder complications were noted. CONCLUSION: We recommend open laparoscopy
      because of its innocuity and easiness. Advantages concern decrease of major
      vascular injuries and early recognition of bowel injuries.

PMID- 12043504
TI  - [Adenocarcinoma of the cervix uteri: a retrospective study of 83 cases].
AB  - The frequency of the adenocarcinoma of cervix uteri is increasing. AIM OF THE
      STUDY: To define the characteristics of the entity. PATIENTS AND METHODS: Between
      1986 and 1992, 83 adenocarcinoma of cervix uteri, were treated at the Ibn Rochd
      Oncology Centre in Casablanca. It's a retrospective study with univariate
      analysis of the prognostic factors. This analysis was done for patients who were
      followed until the death or have 5 years or more follow up and the survival was
      calculated according the Kaplan & Meier method at 5 years. The local and regional
      recurrence factors were evaluated statically according the chi 2 and those for
      survival rate according the Logrank test. RESULTS: The frequency increased during
      the period with 2.1% in 1986 and 8.2% in 1992. The median of aged was 49 years.
      Fifty one patients have localised stage. Combined radiotherapy and surgery was
      performed in 66 cases and 17 received radiation alone. The loco-regional control
      was obtained in 83% among 73 available patients for results. The univariate
      analysis showed that the histological type was not a significant factor. However,
      age, tumor size, stage, histological grade and lymph node involvement were
      significant factors. These factors, the degree of differentiation and the lymph
      node involvement were significant for the 5-years survival. CONCLUSION: The
      prognosis factors of the cervix uteri adenocarcinoma are, size tumor more than 4
      cm, lymph node involvement, microscopic involvement to the parameters and
      positives excision merges.

PMID- 12043505
TI  - [Pregnancy, tuberculosis and inappropriate antidiuretic hormone secretion].
AB  - We report a pregnant woman presenting with seizure secondary to hyponatremia by
      inappropriate antidiuretic hormone secretion. Aetiology was unknown urinary and
      lung tuberculosis. This case report presents diagnosis strategy of inappropriate
      antidiuretic hormone secretion and the arguments for its aetiology.

PMID- 12043506
TI  - [Sex and love].
AB  - Sex is established as soon as spermatozoid and ovule have met. Except for rare
      cases of ambiguity, you clearly see at birth whether the baby is a boy or a girl.
      This mere factual difference evolves into sexual identity through childhood and
      fully blossoms in teenagers. Is sexual maturity happily completed then? Not
      always. Unrational sexual pulsions and survival instincts belong to the whole
      animal species but for man's child, as soon as he is born and until he dies,
      feelings will be intimately involved with sexuality in all its various stages.
      Teenagers' sexuality is both the end stage of childhood sexuality, being as such
      full of psychological traps, and the beginning of a search for a balance between
      sex and love, which is perhaps our modern way of trying to achieve self
      fulfilment and happiness.

PMID- 12043507
TI  - [In situ adenocarcinoma of the uterus cervix: difficulties of its
      cytohistological diagnosis].
AB  - In situ adenocarcinoma is regarded as the precursor of invasive adenocarcinoma.
      It is asymptomatic and early diagnosis relies solely on cytopathologist. It is
      usually discovered on a cone for squamous CIN. When diagnosis is made by biopsy,
      conisation is required to exclude invasive adenocarcinoma. Lesion is
      histologically characterised by epitheliomatous transformation of endocervical
      glands without invasion of the chorion. By the appearance of glandular cells,
      different histological varieties are described. They have no influence on the
      prognosis. Several benign lesions may mimic adenocarcinoma: tubal metaplasia,
      glandular atypia due to inflammation or irradiation, mesonephric remnants and
      microglandular hyperplasia. Precursor lesions (atypical hyperplasia, glandular
      dysplasia, CIGNI and II) are badly morphologically defined. Preferential location
      of in situ adenocarcinoma is the transformation zone. Because of this topography,
      if the surgical margins are disease free, conisation alone may be adequate
      therapy. HPV infection (mainly HPV 18) are incriminated in its pathogenesis.

PMID- 12043508
TI  - [Use of misoprostol in gynecology and obstetrics].
AB  - Although misoprostol is a widely used medication in gynecology and obstetrics, it
      is an off label drug that is not officially approved and used in an illegal way.
      This literature review shows its efficacy and safety in most of its indications
      in gynecology and obstetrics. Misoprostol is effective in cervical priming before
      curettage or operative hysteroscopy. Medical abortion using a combination of
      mifepristone followed 36 to 48 h by misoprostol seems efficient. The induction of
      abortion after 17 weeks gestation can be achieved also by using misoprostol. The
      cervical ripening and induction at term by misoprostol cannot be a first line
      therapy because of its sides effects on uterine contractility and fetal heart
      rate. After failure of other methods, it could be proposed. The use of
      misoprostol in prevention and management of postpartal hemorrhage seems efficient
      but more studies are needed particularly randomised contre sulfoprostone.

PMID- 12043509
TI  - [Molecular genetic testing in amniotic fluid].
AB  - The recent progress in cloning and sequencing the genes responsible for genetic
      diseases and the use of Polymerase Chain Reaction (PCR) allow to test genetic
      diseases with a few quantity of DNA. Amniotic cells are easily sampled by using
      amniocentesis. When abnormal ultrasound allows to suspect a genetic disease, PCR
      on DNA from amniotic cells is a very efficient test to confirm or exclude the
      presence of the disease. Microsatellites sequences can be used on amniotic cells
      as a rapid test for chromosomal aneuploidies.

PMID- 12043510
TI  - [It is possible to prescribe a hormonal replacement therapy for a woman with
      proliferative mastopathy with atypia].

PMID- 12043511
TI  - [It is not advisable to prescribe hormonal replacement therapy to a woman with
      proliferative mastopathy with atypia].

PMID- 12043512
TI  - [Prenatal prevention of risk factors in neonatal bacterial infections].

PMID- 12043513
TI  - [Should abortion laws in France be relaxed again?].

PMID- 12043514
TI  - ["Casual victims" TVT or Burch celioscopy?].

PMID- 12043515
TI  - [Medically assisted reproduction and the desire for a child by HIV infected
      couples: has the time come for a change in attitude?].

PMID- 12043516
TI  - [Medically assisted reproduction and the desire for a child by HIV infected
      couples: has the time for a change in attitude come?].

PMID- 12043517
TI  - Pressure-pain threshold variation in temporomandibular disorder myalgia over the
      course of the menstrual cycle.
AB  - AIMS: To evaluate the influence of the menstrual cycle on pressure-pain
      thresholds (PPTs) in patients with masticatory myalgia. METHODS: Fluctuations in
      pain sensitivity during 2 consecutive menstrual cycles were assessed in 15
      normally menstruating patients with a myogenous temporomandibular disorder (TMD).
      Muscle pain was measured by the use of pressure algometry and a visual analog
      scale (VAS). The McGill Pain Questionnaire was used to assess the sensory,
      affective, and evaluative dimensions of the pain. RESULTS: Since 5 patients
      dropped out of the study due to pregnancy, unexpected menstrual cycle
      irregularities, or personal problems, statistical analysis was performed on 10
      patients. Time had a significant influence on the pain condition. The PPTs of all
      muscle sites increased significantly and progressively over time by 16% to 42% in
      the follicular and luteal phases. PPTs remained low in the perimenstrual phase.
      The VAS pain rating did not correspond well with the PPTs, and the statistical
      analysis showed that the VAS ratings could not be used as predictors for the PPT
      measurements or detect the differences between cycle phases. The sensory,
      affective, and evaluative dimensions of the pain were significantly lower at the
      end of the trial. CONCLUSION: These data suggest a significant influence of the
      menstrual cycle on pain report and a nonspecific improvement of the chronic
      myogenous TMD.

PMID- 12043518
TI  - Temporomandibular disorders after whiplash injury: a controlled, prospective
      study.
AB  - AIMS: Whiplash injury to the neck is often considered a significant risk factor
      for development of temporomandibular disorders (TMD), and has been proposed to
      produce internal derangements of the temporomandibular joint (TMJ). Few studies,
      however, have examined TMD-related pain in acute whiplash patients compared with
      a matched control group. The aim of the present study was to assess pain and
      sensorimotor function in the craniofacial region in an unselected group of
      patients sustaining a motor vehicle accident involving a rear collision. METHODS:
      Prospectively, 19 acute whiplash patients exposed to a motor vehicle accident
      involving a rear collision participated in a study of TMD. The control group
      consisted of 20 age- and gender-matched ankle-injury patients. Participants were
      seen within 4 weeks and again at 6 months post-injury. The masticatory system was
      examined in accordance with the research diagnostic criteria. Participants
      underwent structured interviews, filled out the McGill Pain Questionnaire (MPQ),
      and had their masticatory system examined by a trained dentist, blinded to their
      diagnosis. Pain detection threshold (PDT) to pressure stimuli, and maximal
      voluntary occlusal force (MVOF) were obtained at each visit. RESULTS: One
      whiplash patient and 1 ankle-injury patient had jaw pain at the first visit.
      Palpation scores of the TMJ and the summated palpation scores only tended to be
      higher in patients sustaining a whiplash injury than in ankle-injury controls at
      the first visit. However, MPQ, TMD symptoms and signs, MVOF and PDT were not
      significantly different in whiplash-injury and ankle-injury patients after 4
      weeks and 6 months. CONCLUSION: TMD pain after whiplash injury and ankle injury
      is rare, suggesting that whiplash injury is not a major risk factor for the
      development of TMD problems. Further studies are needed to identify which other
      factors may contribute to TMD pain.

PMID- 12043519
TI  - Routine dental care in patients with temporomandibular disorders.
AB  - AIMS: While a significant number of therapeutic models have been suggested for
      management of orofacial pain and limited opening in patients experiencing
      temporomandibular disorders (TMD), little attention has been given to the issue
      of routine daily care activities, such as toothbrushing and flossing. The purpose
      of this study was to develop an understanding of the extent to which TMD patients
      experience difficulty in performing routine daily mouth care. METHODS: Forty
      patients seeking care for TMD in the Orofacial Pain Center at the University of
      Kentucky College of Dentistry were age- and gender-matched to a group of general
      dentistry patients not experiencing TMD. Participants completed a survey of oral
      health habits, and a clinical exam. RESULTS: Results indicated that TMD patients
      felt their discomfort had created more difficulty with daily mouth care as
      compared with the general dentistry patients (P < .000). Most TMD patients,
      however, continued with routine daily mouth care, except for 15% who reported an
      inability to floss on a regular basis. Also, a majority of TMD patients (63%)
      reported a change in seeking routine professional care because of their disorder
      (P < .000). CONCLUSION: The present data indicate the need for TMD patients to
      receive information concerning routine daily mouth care and visits for
      professional dental care. The results are discussed in terms of the strategies
      that dental care providers need to develop in order to address the significant
      consequences of orofacial pain on regular dental care.

PMID- 12043520
TI  - Mandibular movement characteristics of an anterior disc displacement with
      reduction.
AB  - AIMS: According to the Research Diagnostic Criteria (J Craniomandib Disord
      1992;6(4):301-355), an anterior disc displacement with reduction (ADD) is
      characterized by reciprocal clicking with the opening click occurring at a mouth
      opening at least 5 mm greater than that of the closing click. The aim of this
      study was to test whether the 5-mm criterion of the RDC is characteristic for a
      click due to an ADD. METHODS: From 30 participants with a unilateral ADD,
      recordings of mandibular movements with 6 degrees of freedom as well as joint
      sound recordings were made. The participants performed free open movements and
      loaded closing movements. RESULTS: In 8 joints (27%), the 5-mm criterion was not
      fulfilled. For 2 participants, the click while closing occurred with an even
      larger mouth opening than that while opening. Recordings of the condylar
      movements showed that the opening clicks occurred over a broad range of the
      opening movement, whereas all the closing clicks occurred just before the condyle
      reached its terminal position in the fossa. CONCLUSION: The 5-mm criterion of the
      RDC is not characteristic of all anterior disc displacements with reduction.

PMID- 12043521
TI  - Radiographic signs in the temporomandibular joint in Reiter's disease.
AB  - AIMS: To investigate whether involvement of the temporomandibular joint (TMJ) can
      occur in men with Reiter's disease (RD). METHODS: Forty-nine men with RD and 49
      individually matched (gender, age and dentition type) controls with no known
      general joint disease were screened for findings in the TMJ by panoramic
      tomography. RESULTS: Duration of subjective symptoms (e.g., pain) in the
      masticatory system correlated with duration of RD (P = .05). In the RD group,
      severity of clinical signs of symptoms correlated with the progressive form of RD
      (P = .01), number of affected joints (P = .0001), and involvement of the cervical
      (P = .0001) and lumbar spine (P = .05). Patients with RD more frequently had
      radiographic findings (33%) in the condyle of the TMJ than did controls (10%) (P
      = .002). The most characteristic radiographic sign in the condyle in the RD group
      was unilateral erosion (12%). CONCLUSION: Patients with RD often have erosion
      causing pain and dysfunction in the TMJ. Potential masticatory system problems
      for such patients should be brought to the attention of dentists and physicians.

PMID- 12043522
TI  - Magnetic resonance imaging characteristics of synovial chondromatosis of the
      temporomandibular joint.
AB  - AIMS: To determine the characteristic magnetic resonance imaging (MRI) findings
      of synovial chondromatosis of the temporomandibular joint (TMJ). METHODS: MRI was
      carried out in 11 cases of synovial chondromatosis of the TMJ, which had been
      confirmed surgically and histologically. RESULTS: Severe bony changes were not
      apparent. One or more hypointensive loose bodies were seen in 7 of the 11 cases.
      A considerable amount of synovial fluid, often with capsular expansion, was a
      common finding. CONCLUSION: A diagnosis of synovial chondromatosis of the TMJ
      must be considered when the amount of synovial fluid is abnormally large and the
      disc position is fairly normal, as seen on closed- and open-mouth MRI of the TMJ,
      without any associated severe changes in disc shape or bony structure.

PMID- 12043523
TI  - Teaching evidence-based approaches to orofacial pain.

PMID- 12043524
TI  - Complex regional pain syndrome in the head and neck: a review of the literature.
AB  - This article reviews the features of complex regional pain syndrome (CRPS),
      including its pathophysiology, diagnosis, and treatment. CRPS is a pathology that
      has been described as occurring almost always in a limb, but this review provides
      a focus on the literature reporting cases in which the face, head, and neck were
      affected. Very few cases were found that seemed to meet the International
      Association for the Study of Pain criteria for the disease. The clinical
      characteristics were similar to those of CRPS elsewhere in the body, with the
      main features being burning pain, hyperalgesia, and hyperesthesia starting after
      a trauma to the craniofacial region. Physical signs were reported less
      frequently. The treatment of choice was seen to be a series of stellate ganglion
      anesthetic blocks, which resulted in a good outcome in all the cases reviewed.

PMID- 12043525
TI  - Use risk adjusters to allocate capitation revenue.

PMID- 12043526
TI  - HMO physician incentives and trust: are patients bothered?

PMID- 12043527
TI  - Use these benchmarks to evaluate hospital cardiovascular care.

PMID- 12043528
TI  - HMO use of capitation for physicians continues to grow.

PMID- 12043529
TI  - Successful negotiating among the tribes in your organization.
AB  - As the author of Tribal Warfare in Organizations, I have spent my career
      refereeing conflicts among the tribes in organizations. Health care has more
      tribal battles than most other work settings. Although some people swear that
      health care attracts a higher percentage of cantankerous personalities, this is
      not true. Complexity breeds tribal tensions, and health care is a very complex
      environment. There are more professions, more highly complex services, and fewer
      resources.

PMID- 12043530
TI  - Social capital: the value-creating, performance-boosting phenomenon.
AB  - Does it really matter if you don't have a great relationship with your employer
      and co-workers? Hospitals are a good place to find the answer. A recent study in
      the Journal for Health Affairs indicates that less than 50 percent of nurses
      report that their hospital cares about their concerns, provides opportunities in
      decisionmaking, or acknowledges their contribution to patient care. How hospitals
      deal with these issues will determine which flourish and which flounder.

PMID- 12043531
TI  - Going to school ... at work.
AB  - The following article is the last in a series that focuses on unique and
      effective human resources recruiting and retention tactics in Michigan hospitals.
      The education of health care employees is key to having a qualified work force.
      And paying for the further education of current employees is an easy way to
      supply a hospital with the registered nurses they need.

PMID- 12043532
TI  - The foundation of business communications.
AB  - Today, consumers are directing their own health care and making their own
      decisions. They have access to vast amounts of information and education. They
      are also spending their own out-of-pocket money on health care.

PMID- 12043533
TI  - Reading, writing and good health.
AB  - At a time when Detroit's health systems are struggling with decreasing
      reimbursements, funding shortfalls and diminishing resources, the city's health
      systems have come together and put aside competition to increase access to care
      for the city's children.

PMID- 12043534
TI  - Presenting a united front in Lansing.
AB  - Over the past five fiscal years--a period of unprecedented economic prosperity
      that witnessed overall funding increases for education, corrections and other
      state programs of 19 percent--Medicaid funding for Michigan's nonprofit hospitals
      increased by a meager 3 percent. Why aren't nonprofit hospitals getting a fair
      shake from the legislature in Lansing?

PMID- 12043535
TI  - Coaching skills for employee development.
AB  - Chief nursing officers, in a national research study called the Nursing
      Leadership Edge, ranked employee coaching and development as the number one
      leadership skill required in their jobs. As one chief nursing officer said, "Our
      success depends on having a support team that is successful and perceived by
      others as being successful. We need to develop our staff to ensure their
      success."

PMID- 12043536
TI  - Taking the initiative.
AB  - Developing a 'culture of safety' is a significant undertaking that requires both
      strong leadership and multidisciplinary efforts. There are a number of internal
      and external pressures being exerted on hospitals to substantially improve
      patient safety. This article will highlight some key actions that William
      Beaumont Hospital in Troy has made in recent years with respect to improving
      patient safety.

PMID- 12043537
TI  - Controlling information technology costs, Part 3.
AB  - Health care executives are increasingly frustrated by Information Technology
      (IT). Although our industry is often accused of underinvesting in technology
      (hospitals average 2-3 percent of their costs in IT, compared to other industry's
      8-10 percent), when IT investments are made, they fail to reflect demonstrable
      return to the bottom line. Yet the effective deployment of technology is so
      critical to the success of the organization and can in itself cause the failure
      of a health care system.

PMID- 12043538
TI  - Building unity.
AB  - Changes in how we pay for health care, an increasingly rapid rate of
      technological and medical innovation, the introduction of competition, the
      development of systems, the growth of complementary medicine and a host of other
      changes have made it hard for health care leaders to maintain unity and a spirit
      of collegiality that were once hallmarks of the field.

PMID- 12043539
TI  - A child with earache.

PMID- 12043540
TI  - A child with earache.

PMID- 12043541
TI  - Comments on Malcolm Fraser.

PMID- 12043542
TI  - Redbook and PSA testing.

PMID- 12043543
TI  - Controversies in HRT.
AB  - BACKGROUND: Short term hormone replacement therapy (HRT) use is well established
      for menopausal symptom relief. However, the rates and duration of HRT use are
      increasing in Australia while the benefits and risks of long term HRT remain
      controversial. OBJECTIVE: To review the evidence for the use of HRT for the
      prevention of cardiovascular disease (CVD) and osteoporosis as well as the
      increased risks of thrombosis and, potentially, breast cancer. DISCUSSION:
      Cardiovascular disease and osteoporosis are common in western countries.
      Extensive epidemiological data suggests that HRT may protect against CVD and
      fracture, potentially offering significant long term health benefits to
      postmenopausal women. However, limited controlled trials focusing on CVD
      prevention have suggested no benefit from HRT. Also, there is limited controlled
      fracture end point data to support HRT use for the treatment of osteoporosis.
      Furthermore, potential benefits of long term HRT use need to be balanced against
      the risks of use, including increased thrombosis and potentially as suggested
      from epidemiological studies, increased breast cancer.

PMID- 12043544
TI  - Premature menopause. 'I feel like an alien'.
AB  - BACKGROUND: Those women who experience premature menopause require special needs
      as the consequences to their health, physically and emotionally, both in the
      immediate and the long term are more significant. OBJECTIVE: To present a
      management and treatment profile. DISCUSSION: The incidence of spontaneous
      premature menopause is approximately 1% of women under 40 years with an increase
      up to 8-10% when menopause is the consequence of gynaecological surgery,
      chemotherapy and radiotherapy. Diagnosis is often delayed. Careful investigation
      should occur over a number of months to confirm the diagnosis. Sensitive
      discussion of the diagnosis and management in a supportive manner will help the
      young woman to adjust to the menopause and accept appropriate hormonal therapy.
      Many other issues, including emotional, sexual, reproductive, societal and
      relationships may also need help.

PMID- 12043545
TI  - Menopause. A treatment algorithm.

PMID- 12043546
TI  - Loss of libido in menopausal women. Management issues.
AB  - BACKGROUND: Due to a complex interplay of sociocultural factors, past
      experiences, relationships and hormones, a woman's experience at menopause and
      beyond is highly individual. A variety of external, often stressful, life events
      can be occurring at this time in a woman's life, all impacting on her individual
      symptom profile. Menopause is a natural event in a woman's life cycle and loss of
      libido may be one of a multitude of symptoms experienced around this time. In
      fact, the decline in sexual interest commonly precedes the onset of a natural
      menopause, even though many women do not report their loss of libido until the
      menopause, when symptoms may be exacerbated. OBJECTIVE: To review contributing
      factors and treatment options available for menopausal women experiencing loss of
      libido. DISCUSSION: With increasing awareness, knowledge and discussion about
      sexual health issues, there are an increasing number of women seeking advice and
      treatment for low libido. The introduction of the oral contraceptive pill in the
      '60s; the increasing use of HRT for menopausal symptoms; the availability of
      drugs such as sildenafil; the recent acknowledgement and definition of the
      'female androgen insufficiency syndrome' are all factors which have contributed
      to the so-called 'sexual revolution' whereby women and their doctors--are able to
      feel more comfortable discussing their sexual concerns. Nevertheless, many women
      will not volunteer this information and it is advisable to specifically ask about
      libido and associated symptoms of mood and well being.

PMID- 12043547
TI  - Sexual desire. Menopause and its psychological impact.
AB  - BACKGROUND: Many women present with sexual dysfunction at the menopause. A number
      of researchers have considered the physiological changes that impact on sexual
      function in the menopausal woman, however, less is written about the impact of
      psychological function at the menopause. OBJECTIVE: This article describes the
      importance of psychosocial factors such as mood, past sexual behaviours, body
      image, sociocultural, partner and midlife issues in the treatment and the
      understanding of the menopausal woman who presents with sexual dysfunction.
      Questions that may be asked of patients and possible treatment options will also
      be discussed. DISCUSSION: Research has concluded the multivariate nature of human
      sexuality. It is important that in the treatment and understanding of the
      menopausal woman who presents with sexual dysfunction, that both physiological
      and psychosocial factors are considered.

PMID- 12043548
TI  - Bupropion sustained release. A therapeutic review of Zyban.
AB  - BACKGROUND: Originally developed as an antidepressant, bupropion hydrochloride is
      a selective re-uptake inhibitor of dopamine and noradrenalin which was found to
      reduce nicotine withdrawal symptoms and the urge to smoke. Bupropion came onto
      the Australian market in November 2000 as a 150 mg sustained release preparation
      to be used as an aid to smoking cessation in combination with counselling.
      Following the PBS listing in February 2001, there was a dramatic increase in
      prescribing, and considerable public and professional attention focused on this
      drug. OBJECTIVE: This review summarises the evidence on how bupropion sustained
      release (SR) works, its contraindications and risks, adverse effects, studies on
      efficacy and place in smoking cessation pharmacotherapy. DISCUSSION: Bupropion SR
      is a useful oral and non-nicotine form of pharmacotherapy for smoking cessation.
      Efficacy has been demonstrated in two key published trials. In one of these
      trials efficacy was superior to nicotine patch. There is also evidence of
      efficacy in patients with mild to moderate chronic obstructive pulmonary disease.
      Bupropion SR is contraindicated in a number of conditions where there is an
      increased risk of seizures. This includes patients with a current seizure
      disorder or any history of seizures. It must not be used concurrently with
      monoamine oxidase inhibitors and interacts with medications which can lower the
      seizure threshold. Minor adverse effects such as insomnia, headache, dry mouth
      and nausea are common. Serious adverse effects are rare but include seizures
      (risk of 1/1000) and hypersensitivity reactions. The latter can manifest as skin
      rash and a serum sickness-like reaction.

PMID- 12043549
TI  - Methaemoglobinaemia.

PMID- 12043550
TI  - Lower limb taping.
AB  - This article, the final in this series, describes taping techniques for common
      lower limb problems. Taping can be used to correct abnormal biomechanics (e.g.
      patellofemoral pain), prevent recurrent injury (e.g. ankle taping for
      instability), offload the injured tissue (e.g. acute ankle sprain) or provide
      proprioception awareness (e.g. Achilles tendonitis).

PMID- 12043551
TI  - One pair must last a lifetime. Painless ulcers.

PMID- 12043552
TI  - Aortic dissection.

PMID- 12043553
TI  - A pregnant traveller.

PMID- 12043554
TI  - New technologies. Taming the tiger!

PMID- 12043555
TI  - A matter of life and death.

PMID- 12043556
TI  - The Royal Australian College of General Practitioners. The development--Part 1.
AB  - As general practitioners developed a corporate mentality, they also saw the need
      for a body that would represent them. This led to various medical associations
      and groups of general practitioners. For a variety of reasons, these bodies
      failed to develop until the final emergence of the Royal College of General
      Practitioners....

PMID- 12043557
TI  - Self care strategies for doctors. Assessing our own wellbeing.

PMID- 12043558
TI  - Family Medical Care Education and Research Foundation.

PMID- 12043559
TI  - The presence of medical students in practice consultations. Rates of patient
      consent.
AB  - OBJECTIVE: To measure the frequency of nonconsent encountered by medical students
      and describe the influence of gender. METHOD: An observational study of general
      practice teaching consultations. RESULTS:  SUBJECTS: 63 students (40% female), 67
      general practitioners (30% female), and 2572 patients (56% female). OUTCOME: 3.4%
      of all patients (79% female) did not give consent (4.6% for male students; 1.6%
      for female; OR = 3.0, 95% CI 1.7-5.3). The rates of nonconsent did not vary
      between age groups for men but occurred mainly in the 15-44 years age group for
      women. Male students encountered more nonconsenting female patients than female
      students, particularly in consultations with female GPs. CONCLUSION: Consent to
      allow medical students to be present in general practice consultations is usually
      provided. It is typically declined for male students by young women attending
      women doctors.

PMID- 12043560
TI  - Vaccination among household contacts of chronic hepatitis B carriers by general
      practitioners.
AB  - BACKGROUND: Immunising household contacts of chronic hepatitis B carriers in
      Australia has the potential to substantially reduce the spread of this disease.
      However, little is known about this activity in Australia. METHOD: We identified
      chronic carriers from the northern Sydney area who had positive hepatitis B virus
      (HBV) status detected twice greater than six months apart. We contacted their
      general practitioners, and, with their permission, their patients to conduct
      structured telephone interviews. RESULTS: There were 52 HBV chronic carriers.
      From their 113 household contacts, 22 had current or past HBV infection, 67 had
      been vaccinated, 17 were unvaccinated, and seven had unknown HBV status. Contacts
      of younger carriers were more likely to be vaccinated (p < 0.01). CONCLUSION:
      Most household contacts of chronic hepatitis B carriers have either been exposed
      to, or vaccinated against, HBV. There is still room for improvement by general
      practice in the identification of the contacts of cases of acute HBV infections.

PMID- 12043561
TI  - Management of children after presenting to hospital with acute asthma but not
      requiring admission.
AB  - OBJECTIVE: To examine the treatment of asthma in children aged 4-15 years in the
      12 months following presentation to hospital with acute asthma but not requiring
      admission. METHOD: Questionnaire based survey addressing the child's use of
      health services, contact with general practitioners before presentation, use of
      asthma management plans, symptom frequency, and management of asthma. RESULTS:
      Sixty-six parents (response rate 50%) completed questionnaires. Children usually
      experienced infrequent episodic symptoms of asthma, and had good or excellent
      health (68%). Twenty-two children reported no medical follow up post-emergency
      department (ED). Of the 39 children who had been reviewed by their GP post-ED,
      51% (n = 20) recalled discussing the reasons for presentation to ED with the GP,
      41% (n = 16) had a lung function measurement and 64% (n = 25) had discussed ways
      to better manage the child's asthma to avoid the need for future ED attendance.
      Most parents of children with asthma (n = 57, 86%) recalled the GP explaining how
      to manage their child's asthma, but only 35 (61.4%) recalled the GP ever writing
      down these instructions. CONCLUSION: Children with acute asthma who do not
      require admission may be better managed in the community if there is greater
      recourse to GP care, use of written management guidelines and opportunities for
      additional community care are taken up. Further work is needed to identify
      strategies that will enable GPs to do this.

PMID- 12043562
TI  - [Molecular cloning, characterization, chromosomal assignment, genomic
      organization and verification of SFRS12(SRrp508), a novel member of human SR
      protein superfamily and a human homolog of rat SRrp86].
AB  - We have identified and characterized a novel human serine-arginine-rich (SR)
      splicing regulatory protein 508 (SRrp508) gene that is related to other members
      of the growing SR superfamily, but only homologous to rat (Rattus norvegicus)
      serine-arginine-rich splicing regulatory protein 86 (SRrp86) gene. The full
      length cDNA of 3811 bp for human SRrp508 was cloned through a blast search of
      public databases following the identification of a cDNA contig of 658 bp obtained
      by EST assembly with full robotization in supercomputer in large-scale.
      Structurally, human SRrp508 encodes a polypeptide of 508 amino acids, which
      contains a single amino-terminal RNA recognition motif (RRM) and two carboxy
      terminal domains rich in serine-arginine dipeptides that are highly conserved
      among other members of the SR superfamily. The conserved SR and RRM domains
      emphasize the biological importance of this gene. The SRrp508 gene, which
      contains 12 exons ranging from 0.096 to 2.093 kb and 11 introns ranging from 0.14
      to 5.153 kb, is mapped to the human cytogenetic region 5q11.2-q12.1 using the
      bioinformatic analysis, and it does not link to any other genes. Furthermore, we
      have experimentally cloned and sequenced a cDNA fragment of 1680 bp containing
      the full-length ORF of 1527 bp in this novel human gene by RT-PCR from the single
      stranded human pancreas cDNA library (Clontech), which is fully identical with
      that of the in silico cloning determined by the nucleotide sequencing. Thus, we
      in silico cloned his gene with GenBank accession number of AF459094 identified
      solely by bioinformatic analysis of the nucleotide and protein. This novel gene
      has promotors, TATA-box, several stop codons in the upstream of ORF, and PolyA
      signal in the downstream of ORF. Based on the above results, it can be concluded
      that we have obtained a complete novel human gene. The gene sequence exhibits
      good overall homology to that of rat SRrp86 gene, with 84% and 86% identity over
      the full-length nucleotide and protein, respectively, and with 96% and 86%
      identity over the serine-rich domain (RS) or arginine-rich domain (RA),
      respectively. The full-length sequence exhibits little overall homology to any
      other known protein at either the nucleotide or the amino acid level. The other
      two most closely related proteins, with 34% and 35% identity over the full-length
      protein, respectively, or with 51% and 54% identity over the full-length
      nucleotide of ORF, respectively, are drosophila serine-arginine-rich protein 54
      (SRp54) and human arginine-rich nuclear protein 54 (p54). When comparisons are
      restricted to the RS or RA domains, the percent identity increased for both SRp54
      and p54 are 44% and 54% or 38% and 43%, respectively. These results well
      demonstrate that only the novel human protein of 508 amino acids cloned is the
      human homolog of rat SRrp86, thus correcting the standpoint made by Barnard and
      Patton (Barnard DC, Patton JG. Identification and Characterization of a Novel
      Serine-Arginine-Rich Splicing Regulatory Protein. Molecular and Cellular Biology,
      2000, 20(9): 3049-3057) that human arginine-rich nuclear protein 54 (p54) is the
      human homolog of the rat SRrp86, and suggesting that human SRrp508 is a new
      member of this growing superfamily of SR proteins. SRrp508 has an extensive
      expression profile, and may be a transcriptional factor. On the basis of its
      sequence and functional properties, we have named this protein SRrp508 for SR
      related splicing regulatory protein of 508 amino acids. In summary, by combining
      bioinformatic analysis with experimental verification, we have successfully
      cloned the human cDNA homolog of rat SRrp86, which is verified by a series of
      theoretical and experimental evidence. The HGNC has just given SRrp508 gene entry
      the nomenclature information containing APPROVED SYMBOL: SFRS12; NAME: splicing
      factor, arginine/serine-rich 12; and ALIAS: DKFZp564B176, SRrp86. We have cloned
      this gene for near one year with no person landing the GenBank for registering
      the same gene. Our newly-established technique line will be helpful in
      discovering much more novel human genes.

PMID- 12043563
TI  - Analysis of DNA polymorphism at HLA-A locus by PCR amplification with sequence
      specific oligonucleotide probe in Chinese Han and Uygur populations.
AB  - To determine HLA-A genetic polymorphism in Chinese populations and establish
      ethnic genetic database, 165 Han and 162 Uygur subjects were investigated with a
      non-isotopic and sensitive method PCR-SSOP. 22 alleles were identified in Han
      with the most frequent allele being HLA-A * 1101 (19.7%), followed by * 0201
      (12.72%). Also, 22 alleles were identified in Uygur with * 2407 (17.90%) being
      the most frequent one and the frequencies of following alleles: * 0201, * 0101, *
      3301 were higher than 10%. HLA-A * 0203, * 0205, * 0210, * 0302, * 2403 and *
      3302 were only detected in Han; meanwhile * 0205, * 0211, * 2301, * 2502, * 68012
      and * 6802 were only in Uygur. According to Hardy-Weinberg equilibrium, each
      allele showed no significant (P > 0.05) deviation between the expected frequency
      and the observed one. Heterozygosity (H), discrimination power (DP) and
      probability of paternity exclusion (EPP) of HLA-A locus from Han nationality were
      computed to be 0.9029, 0.9776 and 0.8592; and those from Uygur as 0.9063, 0.9379
      and 0.7885. These results suggest that HLA-A DNA polymorphism and the database of
      two Chinese populations have useful applications in processing forensic casework
      (as personal identification, paternity test), tracing population migration and
      genetic diagnosis.

PMID- 12043564
TI  - [Studies of the deletion and expression of cytokeratin 13 gene in laryngeal
      squamous cell carcinoma].
AB  - In order to investigate the role of Cytokeratin 13(CK13) gene in laryngeal
      carcinogenesis, we detected the deletion of CK13 gene through LOH analysis
      indirectly at DNA level using 5 STR primers within and near CK13 gene in 72 cases
      of laryngeal squamous cell carcinoma, then detected the differential expression
      between 16 cases of paired normal and cancerous tissue by Northern blot, and
      performed immunohistochemistry using well characterized monoclonal antibody
      against CK13 in squamous cell carcinoma of different stages. We found that all of
      the microsatellite loci exist LOH, and the LOH frequencies were 18.03%, 28.13%,
      27.42%, 39.68% and 34.85% at D17S1964E, D17S2092, D17S791, D17S1665 and D17S808
      respectively. The LOH+ cases accounted for 77.78% (56/72), and the frequencies of
      LOH were not related to the type of laryngeal carcinoma and the lymphoid
      metastasis; but significantly related to the differentiation, P < 0.05. CK13 gene
      is expressed significantly higher in 16 cases of normal tissues than in paired
      cancerous tissues, and the immunostain revealed that CK13 was expressed in normal
      laryngeal squamous cell or high differentiation stage, and its expression
      decreased or disappeared in poor ones, P < 0.01. CK13 gene might play an
      important role in the laryngeal carcinogenesis, acting as a novel tumor
      suppressor gene, and may be relevant to laryngeal squamous cell carcinoma
      diagnosis and prognosis. Further research will contribute to conform it.

PMID- 12043565
TI  - [Expression of green fluorescent protein vector by promoter sequence of CYP21
      gene and CYP21P gene].
AB  - After amplification of PCR fragment of -770 bp(-)-1 bp in promoters of CYP21 gene
      and CYP21P gene respectively, the CMV promoter was cut off from pEGFP-N1, the
      vectors were constructed, in which contained promoter areas in CYP21 gene
      (pCYP21) and CYP21P gene (pCYP21P). All pCYP21, pCYP21P, pEGFP-N1(positive
      control) and negative control were transfected respectively into steroidogenic Y1
      cell line, and were observed by inverted fluorescent microscopy and laser
      confocal microscopy. After transient transfection, the cells placed on inverted
      fluorescent microscopy. The appearance of GFP expression observed is as follows:
      pEGFP-N1 at 3 hours; pCYP21 at 7 hours. However, neither pCYP21P nor negative
      control expressed GFP. Laser confocal microscopy showed that pEGFP-N1 and pCYP21
      produced GFP. pEGFP-N1 is stronger than pCYP21, but none of pCYP21P and negative
      control expressed GFP. Different distribution of GFP in Y1 cell could be seen of
      pEGFP-N1 and pCYP21, and the intensity of GFP in nucleus is stronger than
      cytoplasm. Our results further conform that there is a significantly difference
      of GFP expression in Y1 cell line by promoters of CYP21 and CYP21P.

PMID- 12043566
TI  - [Cloning and sequencing of four microsatellite loci in Small Tail Han Sheep].
AB  - Small Tail Han sheep is an excellent local sheep breed in China. Small Tail Han
      sheep has significant characteristics of high prolificacy. The lambing percentage
      averaged 260 percent in Small Tail Han sheep. The genetic detection of 4
      microsatellite loci OarAE101, OarHH35, BM143 and BMS2508 which were closely
      linked to the fecundity gene FecB in Booroola sheep was conducted in 159 sheep in
      Small Tail Han sheep, Dorset sheep, F1 hybzids(Dorset x Small Tail Han sheep).
      The results confirmed the genetic characteristics of codominance of
      microsatellite DNA. The PCR amplified products of microsatellites were detected
      by non-denatured (natural) polyacrylamide gel electrophoresis. The sequences of
      PCR amplification fragment of 6 clones of 4 microsatellite loci in Small Tail Han
      sheep were accepted by GenBank of National Center for Biotechnology Information,
      National Institutes of Health in USA, the GenBank accession numbers were
      AF394445, AF394446, AF394447, AF394448, AF394449, AF394450, respectively. The
      sequence homogeneity between OarAE101 in Small Tail Han sheep in this study and
      the ovine OarAE101 in GenBank was 98 percent. The sequence homogeneity between
      OarHH35 in Small Tail Han sheep in this study and the ovine OarHH35 in GenBank
      was 99 percent. The sequence homogeneity between BM143 in Small Tail Han sheep in
      this study and the bovine BM143 in GenBank was 95 percent. The sequence
      homogeneity between BMS2508 in Small Tail Han sheep in this study and the bovine
      BMS2508 in GenBank was 95 percent. OarAE101, OarHH35, BM143 and BMS2508 in Small
      Tail Han sheep were all perfect microsatellites. These results could provide
      molecular basic data for the research on the germplasm characteristics of Small
      Tail Han sheep.

PMID- 12043567
TI  - Nuclear transplantation of somatic cells of transgenic red carp (Cyprinus carpio
      haematopterus).
AB  - Nuclear transplantation was performed using kidney cells, tail fin cells and
      cultured tail fin cells of 18th passage of the F4 hGH gene transferred red carp
      (Cyprinus carpio haematopterus) as donors and the eggs of loach (Misgurnus
      anguillicaudatus) of Huanghe carp (Cyprinus carpio haematopterus) as recipients.
      Using loach unfertilized eggs as recipients 0.33% of reconstructed embryos
      developed in to neural plate from kidney cells, and 0.1% of reconstructed embryos
      developed in to muscular reaction stage from tail fin cells of F4hGH gene
      transferred red carp. A tatal of 0.4% reconstructed embryos from cultured tail
      fin cells of 18th passage and unfertilized eggs of Huanghe carp developed in to
      myotome stage. All the nuclear transfer embryos were positive for hGH gene by PCR
      analysis. The results suggest that exogenous hGH gene is stable in the F4hGH gene
      transferred red carp, hGH gene exists in all the cells of the F4 transgenic red
      carp. Somatic cell nuclear transfer is an effective pathway for producing
      homogenous transgenic fish, but with low efficiency. The reasons of low
      efficiency of somatic nuclear transplantation may be incompatibility of nuclear
      and ooplasm, incongruity of cell cycle, aberrance of chromosomes, etc.

PMID- 12043568
TI  - [Relationship of T-->A mutation in the promoter region of myostatin gene with
      growth traits in swine].
AB  - A T-->A mutation in the promoter region of porcine myostatin (MSTN) gene has been
      identified in previous work. Associations of the myostatin genotypes with growth
      traits are unknown in swine. The present study attempts to analyze the
      relationship of the mutation with the growth traits which included body weight at
      60 d (BW60), average daily gain from 25 kg to 60 kg(ADG1), average daily gain
      from 60 kg to 100 kg (ADG2) and average daily gain from 25 kg to 100 kg (ADG).
      Data from 165, 275, 276 and 276 unrelated individuals respectively were collected
      from three different swine breeding companies. Detections of the mutation were
      carried out by PCR-RFLP approach. The effect of MSTN genotypes (TT and TA) on
      growth traits was estimated by GLM procedure. The results showed that for ADG2,
      individuals with TA genotype were higher than those of TT genotype (P = 0.052),
      indicating a positive effect for A allele. For BW60, ADG1 and ADG, the effect of
      porcine MSTN genotype was non-significant (P > 0.1). Studies are still necessary
      for examining the effects in "double-muscled" pigs.

PMID- 12043569
TI  - Phylogenetic position of Chinese endemic Drosophila curviceps species subgroup in
      the Drosophila immigrans group.
AB  - In order to investigate the phylogenetic position of Chinese endemic Drosophila
      curviceps species subgroup within the D. immigrans group on DNA molecular level,
      the ITS1 region of ribosomal DNA and part of Adh gene for 12 species represented
      all the five subgroups in D. immigrans group were sequenced. Molecular
      phylogenetic trees were constructed by using parsimony and neighbor-joining
      methods based on ITS1, Adh and combined sequences. In the molecular trees,
      species of the D. curviceps subgroup cluster together, strongly supporting
      establishment of a separating subgroup suggested in an initial morphologic study.
      This subgroup is the sister taxa of the D. quadrilineata subgroup. They are the
      younger subgroups, splitting about 3.4 Mya. The D. hypocausta subgroup is located
      at the base of the molecular tree, diverged first in this group about 9.2 Mya.
      Taking the geographic distribution into account, we can conclude that D.
      curviceps subgroup originated from tropic zones, agreeing with the previous
      morphologic and biogeographic suggestions. The position of D. neohypocausta was
      also discussed in this report and it seems that it is closer to the D. immigrans
      subgroup than to the D. hypocausta subgroup.

PMID- 12043570
TI  - [Generation and characterization of chondrocyte specific Cre transgenic mice].
AB  - A chondrocyte specific transgenic construct (pcol2A1-Cre) containing the
      cartilage specific type II collagen A1 promoter, the Cre recombinase gene and the
      polyA of human growth factor gene was generated. The 9.3 kb DNA fragments were
      recovered from Not I digested fragments and microinjected into 323 fertilized
      eggs. The injected eggs were implanted into the oviduct of 14 female mice. In the
      52 offsprings, there were 10 mice carring the transgene identified by PCR, and
      the efficiency was 19.2%. The col2A1-Cre transgenic mice were crossed with a
      conditional gene targeting mice to check the Cre mediated recombination in
      multiple tissues. The results of the PCR analysis suggested that the Cre
      recombinase was expressed only in cartilaginous tissue and could mediate the
      recombination between the LoxP sites in vivo. The result was further confirmed by
      Southern-blot.

PMID- 12043571
TI  - [Effects of several microsatellite DNA loci on milk production in dairy cattle].
AB  - The amplified fragment length polymorphisms of 7 microsatellite DNA loci linked
      with weaver gene according to the comparative map of mouse and cattle were
      detected in 178 Holstein cattle. Results showed that there were 4 and 6 alleles
      at BM6438 and BMS2321 loci respectively. Two alleles at BMS4020 locus and 5
      alleles at BMS711 locus were detected. Two alleles at INRA117, 3 alleles at CA095
      and 3 alleles at TGLA116 locus were found. Among these 7 microsatellite loci,
      BM6438, BMS711 and BMS2321 were high polymorphic loci, and PIC(polymorphism
      information content) was 0.58, 0.67 and 0.67 respectively. PIC of the moderate
      polymorphic locus TGLA116 was 0.45. BMS4020, INRA117 and CA095 were low
      polymorphic loci with PIC of 0.06, 0.05 and 0.05 respectively. Effects of BM6438,
      BMS2321, BMS711 and TGLA116 on milk production traits were analyzed with PROC GLM
      of SAS. Results showed that the four loci had no significant effect on milk yield
      of Holstein cattle, effect of BM6438 and BMS711 on milk composition was not
      significant either(P > 0.05). BMS2321 had a significant effect on protein yield
      and protein percentage(P < 0.01). The effect of TGLA116 on protein yield and
      protein percentage reached a significant level at P < 0.05.

PMID- 12043572
TI  - [Studies of F1 of transgenic allotetraploid hybrids of Carassius auratus red var.
      (Female) x Cyprinus carpio (Male)].
AB  - The tetraploid fish has been developed by assortative breeding the hybrids of
      Carassius auratus red var. (Female) x cyprinus carpio (Male), which has the
      stable genetic characters and can reproduce themselves. An "all-fish" recombinant
      DNA construct (pCAgcGHc) containing common carp beta-actin gene promoter and cDNA
      for grass carp (Ctenopharyngodon idella) growth hormone gene was introduced into
      fertilized eggs of the allotetroploid fish through microinjection as soon as
      artificial insemination was done. Artificial insemination was carried out between
      the female and the male transgenic allotetraploid fish which contain the "all
      fish" recombinant DNA construct (pCAgcGHc) and are the biggest in the size. Fifty
      F1 samples of transgenic allotetraploid fish of 150 days and 50 allotetraploid
      fish (regarded as the control) were chosen, and the weight and the body length of
      each were measured, the results showed that F1 of transgenic allotetraploid fish
      of 150 days had obvious growth dominance compared with the control. Genomic DNA
      of tail fin was extracted from 20 F1 of transgenic allotetraploid fish of 150
      days and the control. Proper primers were introduced to check whether the sample
      had the transgene. Pa, the upstream primer, is located in beta-actin promoter,
      and Pg, the downstream primer, is located in growth hormone cDNA for grass carp
      (gcGHc). The transgene was detected in 90% F1 of transgenic allotetraploid fish
      in tail fin DNA by polymerase chain reaction (PCR) amplification. Sperm could be
      squeezed out from a few F1 of transgenic allotetraploid fish of 150 days,
      however, this phenomenon did not exist in the controls. The importance of forming
      the pure line of transgenic allotetraploid was elucidate in the paper.

PMID- 12043573
TI  - [Prediction of yield and yield components in hybrid rice by using molecular
      markers].
AB  - Yield and yield components in hybrid rice were investigated using AFLP, RAPD and
      SSR markers. Ten restorer and five male-sterile lines were crossed in all
      possible pairs resulting in 50 crosses. Positive loci, effect-increasing loci,
      effect-decreasing loci and non-environmental loci were selected from the 931
      marker loci surveyed in the 15 parental lines and their correlation with yield
      and yield components were analyzed. The results indicated as follows (1) The
      correlation between genetic difference and yield and yield components calculated
      on all three molecular loci failed to reach significant level for most of the
      traits investigated and can not be used to predict yield and yield components
      directly. (2) Positive loci were of limited usefulness in the prediction of yield
      and yield components for their variation with different traits investigated
      despite that they can improve the correlation coefficient in some degree. (3)
      Effect-increasing and effect-decreasing loci can greatly improve correlation
      coefficient and may be used to predict the yield and yield components for their
      consistence with the environment. (4) The coefficient based on non-environmental
      loci was high though it was a bit lower than that based on effect-increasing and
      effect-decreasing loci. It indicated that environment had great effect on yield
      and yield components in rice.

PMID- 12043574
TI  - [Genetic diversity revealed by ISSR molecular marker in common wheat, spelt,
      compactum and progeny of recurrent selection].
AB  - It is important to estimate the genetic diversity between the parents for
      improving the heterosis of hybrid wheat. In this study, ISSR(inter-simple
      sequence repeat) marker was used to measure the genetic diversity within and
      among common wheat (Triticum aestivum L.), spelt (Triticum spelta L.), compactum
      (Triticum compactum Host.) and progeny of foreign wheat-based recurrent
      selection, and the possibility of establishing the new heterotic group was also
      assessed. Forty seven genotypes were used for ISSR analysis, which included 14
      common wheat, 10 spelt wheat, 11 compactum and 12 progeny of recurrent selection.
      Eleven of 33 ISSR primers that can produce distinguishable bands were selected
      for PCR amplification. A total of 238 bands were amplified, among which 207 (87%)
      bands were polymorphic. The polymorphic bands amplified by each primer ranged
      from 11 to 38, with an averaged of 18.8. The percentage of polymorphic band
      (80.3%) in common wheat was higher than that in progeny of recurrent selection
      (78.7%), spelt (75.0%) and compactum (74.9%). The 238 polymorphic products were
      used to calculate Nei's similarity index (GS) and the genetic distance (GD). It
      was found that the mean genetic distance between different wheat types (0.3115
      0.3442) was obviously higher than that within common wheat (0.2743), spelt
      (0.2351), compactum (0.2622). In addition, progeny of recurrent selection also
      showed much higher genetic distance with other three wheat types (0.3217, 0.3256,
      0.3198). The cluster analysis was performed based on the genetic distance (GD)
      matrix by using UPGMA method. Common wheat, spelt, compactum and progeny of
      recurrent selection were classified into four different groups. In this study,
      ISSR marker was firstly used to assess genetic diversity among common wheat,
      spelt, compactum and progeny of recurrent selection, and can differentiate the
      wheat cultivars (lines) that selected from the same cross combination. It was
      concluded that spelt, compactum and progeny of recurrent selection can be used to
      diversify the genetic basis for hybrid wheat breeding and improve heterosis. It
      is possible to establish the wheat heterotic group by ISSR marker.

PMID- 12043575
TI  - [Identification, mapping, and application of a chromosome-specific RAPD marker
      from Haynaldia villosa].
AB  - Random amplified polymorphic DNA (RAPD) analysis was performed on common wheat of
      Chinese Spring, addition lines of H. villosa chromosome in CS and H. villosum
      from different accessions with 100 random 10-base primers. A chromosome-specific
      polymorphic DNA segment for H. villosa, OPF02(750), was obtained from all
      addition lines of H. villosa chromosome in CS and H. villosum which belong to
      different accessions. The result amplified by primer OPF02 of all addition lines
      of H. villosa chromosome in CS indicated that all the seven pairs of H. villosa
      chromosomes contain OPF02(750) segment. There was no OPF02(750) in all Triticum
      aestivum and T. durum tested. Using OPF02, We confirmed that NAU302, an addition
      line of H. villosa chromosome 3V, had lost its chromosome 3V of H. villosa.
      Therefore, OPF02(750) is specific to chromosomes of H. villosa, and could be used
      as a molecular marker for detection of chromosome of H. villosa in wheat.

PMID- 12043576
TI  - [Characterization of an ultra-violet inducible gene that encodes glutathione S
      transferase in Arabidopsis thaliana].
AB  - Glutathione S-transterased (GSTs) are a highly divergent gene family. They play
      important roles not only in many stress responses, but also in plant growth and
      development. To understand whether the GST can protect plant from the damage of
      ultra-violet (UV) radiation, a UV inducible GST gene was isolated from an
      Arabidopsis cDNA library. The plant expression vector containing the GST cDNA was
      constructed and transferred into Arabidopsis thaliana plants by the Agrobacterium
      mediated vacuum method. Molecular genetic analyses showed that the overexpression
      of the UV inducible GST could increase the tolerance of the transgenic plants to
      UV radiation.

PMID- 12043577
TI  - [Copia-like retrotransposon in Amaranthus].
AB  - This study analyzed the characteristics of reverse transcriptase sequences of
      copia-like retrotransposons in Amaranthus via PCR amplification and sequence
      approaches. The results are as follows: (1) The reverse transcriptase sequences
      of copia-like retrotransposons were detected in all 30 Amaranthus accessions
      studied, indicating that this class of retrotransposons is ubiquitous in
      Amaranthus; (2) Twenty-eight reverse transcriptases in A. quitensis were cloned
      and sequenced, showing extensive heterogeneity in base deletion mutation and stop
      codon mutation; (3) Cluster and alignment analyses of the 28 sequences and other
      published sequences of the reverse transcriptase from other species (such as
      rice, tomato and Drosophila) showed that the copia-like retrotransposons in A.
      quitensis have a close relationship with those in dicot and monocot plants. The
      evolution of copia-like retrotransposons in A. tricolor, which might be of the
      same origin as the copia and 1731 in Drosophila, was discussed.

PMID- 12043578
TI  - [Production and cytogenetics of hybrids of Ogura CMS Brassica campestris var.
      purpuraria x Raphanus sativus x Brassica napus].
AB  - Crosses of Ogura CMS Brassica campestris var. purpuraria x Raphanus sativus x
      Brassica napus were made and four hybrids were produced. One plant (PRN-1) was
      mosaic with yellow and milk white flowers and some flowers had both yellow and
      white petals. The others (PRN-2, -3, -4) had white flowers. PRN-4 had degenerated
      anthers, the other three had three to six anthers and could produce some pollens,
      but the pollens of PRN-2 were unstainable by I2-KI solution. PRN-2 had four
      normal honey glands, PRN-1 and PRN-3 had two, and PRN-4 had none. PRN-2 had
      normal leaf color and the other three showed different degrees of chlorophyll
      deficiency at low temperature. The chromosome number of PRN-1 was 2n = 38 and had
      the mean chromosome paring configuration of 14.67 I + 10.07 II + 1.06 III, and
      its chromosome set constitution might be AACR. This chromosome constitution may
      be due to the fertilization of female gamete of n = 19 (AR) with male gamete of n
      = 19 (AC) from B. napus. The occurrence of mosaic flower color in this plant may
      be attributed to the chromosome abnormalities caused by wide hybridization, such
      as chromosome deficiency and the formation of chromosome fragments and chromosome
      bridges. The chromosome number of PRN-2 was 2n = 35 and the mean chromosome
      paring configuration was 13.89 I + 8.33 II + 1.33 III + 0.11 IV. The chromosome
      number of PRN-3 was 2n = 33 and the mean chromosome paring configuration was
      14.00 I + 7.82 II + 1.00 III + 0.09 IV. The chromosome number of PRN-4 was not
      determined as there was no pollen mother cell formation. Chromosome bridges and
      laggards were observed in PRN-1-3. Some seeds were harvested from PRN-1-3 but
      none was harvested from PRN-4 when backcrossed with B. napus. It seems possible
      for us to overcome the chlorophyll deficiency and honey gland abnormality and
      restore the male fertility in Ogura CMS by introduction of the nucleus of R.
      sativus into this cytoplasmic male sterile line.

PMID- 12043581
TI  - Jonas Bergstrom, MD, PhD (1929-2001): scientist, physician, researcher, mentor,
      musician, and friend.

PMID- 12043582
TI  - Experimental study on apoptosis of HL-60 cell induced by arsenic trioxide.
AB  - OBJECTIVE: To explore the mechanism of arsenic (arsenic trioxide, AS2O3) in
      treating leukemia. METHODS: The in vitro effect of arsenic trioxide on HL-60
      model double-labelled with PI/AnnexinV-FITC was studied ith flow cytometry.
      Function on telomerase activity was also observed. RESULTS: After the effect of
      arsenic on HL-60 cell line, PI negative/AnnexinV-FITC positive cells increased,
      it mainly acts at the G2-M phase that suggests the apoptosis takes place, mild
      inhibition on telomerase was also found 48 hours later. CONCLUSION: Apoptosis
      induced by arsenic trioxide was the main mechanism in killing or inhibiting
      leukemic cells.

PMID- 12043583
TI  - It's a growth industry.

PMID- 12043584
TI  - [A model concept: medical-nursing patient documentation].

PMID- 12043585
TI  - Hildegard E. Peplau: her contributions. 1978.

PMID- 12043586
TI  - On semantics. 1963.

PMID- 12043587
TI  - Psychotherapeutic strategies. 1968.

PMID- 12043588
TI  - The psychiatric nurse--accountable? To whom? For what? 1980.

PMID- 12043589
TI  - Hildegard E. Peplau: leader, practitioner, academician, scholar and theorist.
      1978.

PMID- 12043590
TI  - The one-to-one nurse-patient relationship. 1980.

PMID- 12043591
TI  - [Humanization versus medicalization].

PMID- 12043592
TI  - [In search of truth as a condition for a happy existence].

PMID- 12043593
TI  - [Nursing care for newborns who are born from diabetic mothers].

PMID- 12043594
TI  - [How to manage an intensive care unit].

PMID- 12043595
TI  - [Learning to "look" at those who approach us].

PMID- 12043598
TI  - Laser ablation construction of on-column reagent addition devices for capillary
      electrophoresis.
AB  - A simple and reproducible technique for constructing perfectly aligned gaps in
      fused-silica capillaries has been developed for postcolumn reagent addition with
      capillary electrophoresis. This technique uses laser ablation with the second
      harmonic of a Nd:YAG laser (532 nm) at 13.5 mJ/pulse and a repetition rate of 15
      Hz to create these gaps. A capillary is glued to a microscope slide and
      positioned at the focal point of a cylindrical lens using the focused beam from a
      laser pointer as a reference. Gaps of 14.0 +/- 2.2 microm (n = 33) at the bore of
      the capillary are produced with a success rate of 94% by ablation with 400
      pulses. This simple method of gap construction requires no micromanipulation
      under a microscope, hydrofluoric acid etching, or use of column fittings. These
      structures have been used for reagent addition for postcolumn derivatization with
      laser-induced fluorescence detection and have been tested for the separation of
      proteins and amino acids. Detection limits of 6 x 10(-7) and 1 x 10(-8) M have
      been obtained for glycine and tranferrin, respectively. Separation efficiencies
      obtained using these gap reactors range from 38,000 to 213,000 theoretical
      plates.

PMID- 12043599
TI  - Depth profiling of heterogeneously mixed aerosol particles using single-particle
      mass spectrometry.
AB  - Infrared laser evaporation of single aerosol particles in a vacuum followed by
      vacuum ultraviolet (VUV) laser ionization and time-of-flight mass spectroscopy of
      the resulting vapor provides a depth profile of the particle's composition.
      Analyzing glycerol particles coated with 60-150-nm coatings of oleic acid using
      either a CO2 laser or a tunable optical parametric oscillator as an evaporation
      laser results in mass spectra that depend on the IR laser power. Low infrared
      laser powers incompletely vaporize particles and preferentially probe the
      composition of the surface layers of the particle, but high laser powers
      evaporate the entire particle and produce spectra representative of the
      particle's total composition. In the limit of low laser power, the fraction of
      oleic acid in the mass spectra is as much as 50 times greater than the fraction
      of oleic acid in the particle, providing a surface-layer-specific
      characterization. The OPO laser provides even more surface specificity, producing
      an [oleic acid]/[glycerol] ratio as much as four times larger (for a 60-nm
      coating) than that obtained using the CO2 laser. The infrared laser power
      required to sample the core of the particle increases with the thickness of the
      coating and is sensitive to changes in the coating thickness on the order of 10
      nm. In contrast to these intuitively appealing results, high CO2 laser powers
      (approximately 90 mJ/pulse) produce mass spectra that, at short delays between
      the CO2 and VUV lasers, show enrichment of the core material rather than the
      coating. Likewise, tuning the OPO to frequencies that are resonant with the core
      material but transparent to the coating also results in selective detection of
      the core. The results suggest that a shattering mechanism dominates the
      vaporization dynamics in these situations.

PMID- 12043600
TI  - Analysis of quantitative proteomic data generated via multidimensional protein
      identification technology.
AB  - We describe the analysis of quantitative proteomic samples via multidimensional
      protein identification technology (MudPIT). Ratio amounts of the soluble portion
      of the S. cerevisiae proteome from cultures of S. cerevisiae strain S288C grown
      in either 14N minimal media or 15N-enriched minimal media were mixed and digested
      into a complex peptide mixture. A 1 x 14N/1 x 15N complex peptide mixture was
      analyzed by single-dimensional reversed-phase chromatography and electrospray
      ionization quadrapole time-of-flight mass spectrometry in order to demonstrate
      the replacement of 14N by 15N under the growth conditions used. After
      conformation of the incorporation of 15N into the labeled sample, three separate
      samples consisting of a 1 x 14N/1 x 15N complex peptide mixture, a 5 x 14N/1 x
      15N complex peptide mixture, and a 10 x 14N/1 x 15N complex peptide mixture were
      analyzed via MudPIT. We demonstrate the dynamic range of the system by analyzing
      a 1:1, 5:1, and 10:1 data set using the soluble portion from S. cerevisiae grown
      in either 14N or 15N-enriched minimal media. The method described provides an
      accurate way to undertake a large-scale quantitative proteomic study.

PMID- 12043601
TI  - The Human Tissue Act 1987.

PMID- 12043602
TI  - Uniform Health Care Information Act 1987.

PMID- 12043603
TI  - Confidentiality of health care information.

PMID- 12043604
TI  - Laetrile.

PMID- 12043605
TI  - Abortion -- Parental Notice of Abortion Act of 1995.

PMID- 12043606
TI  - An act concerning medical treatment of persons afflicted with a terminal
      condition; authorizing a written declaration instructing a physician to withhold
      or withdraw life-sustaining procedures.

PMID- 12043607
TI  - Abortions.

PMID- 12043608
TI  - Abortion.

PMID- 12043609
TI  - Rights of patients.

PMID- 12043610
TI  - Surrogacy.

PMID- 12043611
TI  - Laetrile drug therapy.

PMID- 12043612
TI  - Amygdalin (laetrile).

PMID- 12043613
TI  - Experimental or stimulation of learning process drugs or medications;
      administration to pupils; written consent of parent or guardian and physician.

PMID- 12043614
TI  - Civil rights and medical care for mentally ill.

PMID- 12043615
TI  - Rights of patients.

PMID- 12043616
TI  - Commission on Legal and Ethical Problems in Delivery of Health Care.

PMID- 12043617
TI  - New Jersey Advance Directives for Health Care Act.

PMID- 12043619
TI  - Public policy: newborn infants--test to detect hypothyroidism; objections on
      religious grounds.

PMID- 12043618
TI  - Abortion and sterilization services, liability.

PMID- 12043620
TI  - Laetrile.

PMID- 12043621
TI  - Consent to surgical or medical procedure; requirements.

PMID- 12043622
TI  - Voluntary consent to treatment to be obtained; information to be provided.

PMID- 12043623
TI  - Medical treatment; necessary consent in order to act.

PMID- 12043624
TI  - Confidentiality of health care information act.

PMID- 12043625
TI  - Rights of patients.

PMID- 12043626
TI  - Abortion and sterilization--protection for nonparticipation--procedure.

PMID- 12043627
TI  - Informed consent for abortion.

PMID- 12043628
TI  - Treatment, rights, privileges and expenses of patients generally.

PMID- 12043629
TI  - Inmate records and statistics required of institutions--copy to patient on
      request.

PMID- 12043630
TI  - Care, treatment and rights of mental patients.

PMID- 12043631
TI  - Physician-patient privilege.

PMID- 12043632
TI  - Laetrile.

PMID- 12043633
TI  - Mandatory screening of newborns.

PMID- 12043634
TI  - Consent of patient required for abortion, etc.

PMID- 12043635
TI  - Prohibition of surrogate parenthood agreements -- status of child -- basis of
      custody -- legislative analysis and date of repeal.

PMID- 12043636
TI  - Sterilization.

PMID- 12043637
TI  - Involving hospitalization--examination of patient--hearing--power of court-
      findings--costs.

PMID- 12043638
TI  - Parental notification.

PMID- 12043639
TI  - Protection of reproductive rights.

PMID- 12043640
TI  - Abortion.

PMID- 12043641
TI  - Confidentiality.

PMID- 12043642
TI  - Appointment of special guardian to secure medical treatment for persons under
      eighteen years of age.

PMID- 12043643
TI  - Uniform brain death act.

PMID- 12043644
TI  - Sterilization of mental defectives.

PMID- 12043645
TI  - Penalty for giving away, etc., a live or viable aborted child for
      experimentation.

PMID- 12043646
TI  - Termination of life-support procedures (Natural Death Act).

PMID- 12043647
TI  - Inspection of hospital records.

PMID- 12043648
TI  - Mental health and developmental disabilities code.

PMID- 12043649
TI  - Abortion--fetus--use or sale for experimentation.

PMID- 12043650
TI  - Preservation of life and health of fetus--intentionally taking life of fetus-
      experimentation with fetus.

PMID- 12043651
TI  - Abortion Law of 1975.

PMID- 12043652
TI  - Notice to parent or guardian of minor pregnant woman.

PMID- 12043653
TI  - Informed consent; board of medical examiners standards.

PMID- 12043654
TI  - Right to decline life-prolonging procedures.

PMID- 12043655
TI  - Determination of death (Uniform Determination of Death Act of 1981); natural
      death (Natural Death Act of 1981).

PMID- 12043656
TI  - Minors' consent to diagnostic and lawful therapeutic procedures relating to care
      and treatment for pregnancy or contagious diseases.

PMID- 12043657
TI  - Donation of parts of the anatomy.

PMID- 12043658
TI  - Patient records.

PMID- 12043659
TI  - Informed consent to medical procedures.

PMID- 12043660
TI  - Nursing and intermediate care facilities--rights of patients.

PMID- 12043661
TI  - Written informed consent to electroconvulsive treatments.

PMID- 12043662
TI  - Cancer cure control.

PMID- 12043663
TI  - Natural death act.

PMID- 12043664
TI  - When person deemed medically and legally dead.

PMID- 12043665
TI  - Consent for treatment of breast tumor.

PMID- 12043666
TI  - Living wills.

PMID- 12043667
TI  - Determination of death.

PMID- 12043668
TI  - Bill of rights for residents of long-term care facilities.

PMID- 12043669
TI  - Consent for surgical or medical treatment (Georgia Medical Consent Law).

PMID- 12043670
TI  - Refusal of anitpsychotic medications.

PMID- 12043671
TI  - Legal and civil rights of persons involuntarily detained.

PMID- 12043672
TI  - Use of amygdalin (laetrile).

PMID- 12043673
TI  - Rights of persons hospitalized for mental illness.

PMID- 12043674
TI  - State psychiatric hospitals.

PMID- 12043675
TI  - Experimentation or transportation of aborted fetuses; class A misdemeanor.

PMID- 12043676
TI  - Examination of infants for phenylketonuria.

PMID- 12043677
TI  - Natural death act.

PMID- 12043678
TI  - Right to die.

PMID- 12043679
TI  - Mental health and developmental disabilities.

PMID- 12043680
TI  - Phenylketonuria; congenital hypothyroidism; meniscocytosis.

PMID- 12043681
TI  - Laetrile; effect on license.

PMID- 12043682
TI  - Rights of mental patients: enumerations of rights guaranteed.

PMID- 12043683
TI  - Voluntary admissions; general provisions.

PMID- 12043684
TI  - Human experimentation.

PMID- 12043685
TI  - Abortion.

PMID- 12043686
TI  - Consent to medical treatment.

PMID- 12043687
TI  - Laetrile.

PMID- 12043688
TI  - An act relating to death; providing a definition.  Approved 1973.

PMID- 12043689
TI  - My brilliant career--nurse management. Slice of life. Interview by Lyn Whitfield.

PMID- 12043690
TI  - Membranous laryngopharyngitis.

PMID- 12043691
TI  - [Ill due to nursing care].

PMID- 12043692
TI  - The elusive pathogenesis of von Willebrand disease Vicenza.

PMID- 12043693
TI  - Activation of occult hepatitis B from a seronegative patient after hematopoietic
      cell transplant: a cautionary tale.

PMID- 12043694
TI  - Transjugular intrahepatic portosystemic shunt for treatment of portal
      hypertension due to  extramedullary hematopoiesis in idiopathic myelofibrosis.

PMID- 12043695
TI  - Thromboembolic events during treatment with thalidomide.

PMID- 12043696
TI  - Second response to lower-dose thalidomide in a patient with multiple myeloma.

PMID- 12043697
TI  - In situ localization of tissue factor in human thrombi.

PMID- 12043698
TI  - Systemic non-Hodgkin lymphoma in HIV-infected patients in the era of highly
      active antiretroviral therapy.

PMID- 12043699
TI  - Reduced duration of cytopenias following melphalan conditioning and autografting
      for multiple myeloma.

PMID- 12043700
TI  - ACF with and without plates.

PMID- 12043701
TI  - Mandatory overtime is not going away.

PMID- 12043702
TI  - [Ophthalmology].

PMID- 12043703
TI  - Sequential FISH analysis with rDNA genes and Ag-NOR banding in the lady beetle
      Olla v-nigrum (Coleoptera: Coccinellidae).
AB  - We have characterized the meiosis of Olla v-nigrum by standard analysis,
      performed a NOR study using NOR banding, FISH of rDNA genes and sequential
      FISH/AgNOR analysis, and adapted the FISH methodology to Coccinellidae. The
      chromosome number determined at metaphase I was n = 9 + Xyp. At zygotene it was
      possible to identify the sex vesicle which presented a deeply stained
      heteropycnotic block. Chromosome X is much larger than the y and the two combine,
      forming a "parachute" in metaphase I. FISH analysis using a probe of rDNA genes
      18S, 28S and 5.8S of D. melanogaster was used to map the genes in the sex
      vesicle. The NOR band showed high gene activity in this region. These results
      were confirmed using sequential FISH/Ag NOR analysis. The data obtained for Olla
      v-nigrum agree with the classical hypothesis raised to explain the type of sex
      chromosome association in a parachute format (Xyp) as being due to the presence
      of nucleolar material. The chromosome number and parachute configuration during
      metaphase I in this species agree with the basic karyotype of most Coleopterans.
      The major adaptation of the FISH method was the simultaneous denaturation and
      hybridization that permitted preservation of chromosome morphology, an essential
      factor when the chromosomes are small.

PMID- 12043704
TI  - Cytogenetic characterization of Brazilian Paspalum accessions.
AB  - Chromosome number, pairing relationship and meiotic behavior were evaluated in 24
      Brazilian accessions of different Paspalum species as an initial screening to
      determine which of them might be useful in an interspecific hybridization
      program. The analysis showed that six were diploids, 16 tetraploids and two
      hexaploids. The pairing relationship was typical for the ploidy level and agreed
      with reported data. However, the meiotic behavior after diakinesis was much more
      abnormal than expected considering the pairing relationship. There was a high
      frequency of abnormal tetrads in the majority of accessions.

PMID- 12043705
TI  - [Radiofrequency thermoablation of primary and secondary neoplasms of the liver].

PMID- 12043706
TI  - [Systemic lupus erythematosus and pulmonary fibrosis].

PMID- 12043707
TI  - Hoarding in obsessive compulsive disorder: results from a case-control study.
AB  - Hoarding occurs relatively frequently in obsessive-compulsive disorder (OCD), and
      there is evidence that patients with hoarding symptoms have more severe OCD and
      are less responsive to treatment. In the present study, we investigated hoarding
      symptoms in 126 subjects with OCD. Nearly 30% of the subjects had hoarding
      symptoms; hoarding was twice as prevalent in males than females. Compared to the
      90 non-hoarding subjects, the 36 hoarding individuals had an earlier age at onset
      of, and more severe, obsessive-compulsive symptoms. Hoarders had greater
      prevalences of symmetry obsessions, counting compulsions, and ordering
      compulsions. Hoarders also had greater prevalences of social phobia, personality
      disorders, and pathological grooming behaviors (skin picking, nail biting, and
      trichotillomania). Hoarding and tics were more frequent in first-degree relatives
      of hoarding than non-hoarding probands. The findings suggest that the treatment
      of OCD patients with hoarding symptoms may be complicated by more severe OCD and
      the presence of co-occurring disorders. Hoarding appears to be transmitted in
      some OCD families and may differentiate a clinical subgroup of OCD.

PMID- 12043708
TI  - Reproductive options for HIV-serodiscordant couples.

PMID- 12043709
TI  - Thousands with HIV delay getting care.

PMID- 12043710
TI  - Current or past physical or sexual abuse as a risk marker for sexually
      transmitted disease in pregnant women.
AB  - CONTEXT: Previous studies suggest that a history of physical or sexual violence
      is positively associated with a history of sexually transmitted disease (STD). It
      is important to determine whetherabuse is also a risk factor for current STD
      infection. METHODS: Data were collected from 744 clients of an urban Midwestern
      prenatal clinic who gave birth in 1991-1996. Multiple logistic regression
      analyses were conducted to determine how the odds of having a history of STD or a
      current STD infection are affected by the experience of abuse. RESULTS: Overall,
      30% of the women had a history of STD, and 18% had a current STD infection.
      Results of multivariate analyses showed that compared with nonabused women, those
      who had experienced any type of abuse had nearly twice the odds of having a
      history of infection and of currently having an STD. In separate analyses by
      abuse type, women with a history of only sexual abuse had twice the odds and
      those with a history of both physical and sexual abuse had nearly three times the
      odds of having a current STD, compared with women who reported no abuse.
      CONCLUSIONS: Abused women are at significantly increased risk of having a history
      of STD; abuse is also associated with an increased risk of current infection,
      especially among those with any history of sexual abuse. Future studies should be
      undertaken to better understand the role that abuse may play in relation to STD
      risk.

PMID- 12043711
TI  - Is there a causal link between maltreatment and adolescent pregnancy? A
      literature review.
AB  - CONTEXT: Despite a sizable amount of research addressing the relationship between
      violence and women's reproductive health, it has not been shown whether there is
      sufficient evidence of a causal link between childhood maltreatment and
      subsequent adolescent pregnancy. METHODS: Three databases (Medline, PsychiNFO and
      SocioFile) were searched for studies published between 1980 and 2000 relating
      maltreatment and adolescent pregnancy. The review was limited to empirical
      studies; theoretical articles and those with no women who were aged 21 or younger
      during the research period or when they experienced maltreatment were excluded.
      RESULTS: Fifteen articles on the topic were found All were published after 1989;
      all but one were cross-sectional, were retrospective and relied on recall. All of
      the studies dealt with sexual maltreatment, either alone or in combination with
      other types of maltreatment; few covered emotional abuse or neglect. The studies
      lacked consistent definitions of the various types of maltreatment. Only one
      examined adolescent mothers' relationships with men, and none examined
      relationships with perpetrators. Few dealt with racial and ethnic differences
      related to violence. All lacked a specific theoretical approach. Ten of the
      studies supported a link between maltreatment and adolescent pregnancy, and five
      eitherdid not support a link or qualified the relationship. Substance abuse, poor
      mental health and promiscuity were among the mediating variables examined.
      CONCLUSIONS: Because recent studies have reached conflicting findings, had
      methodological weaknesses and lacked theoretical grounding, whether a causal link
      exists between maltreatment and adolescent pregnancy remains an unanswered
      question.

PMID- 12043712
TI  - HIV counseling and testing: women's experiences and the perceived role of testing
      as a prevention strategy.
AB  - CONTEXT: It is unclear why women decide to undergo testing for HIV, and how
      positive and negative testresults impact their sexual behavior. METHODS: A sample
      of 360 family planning clinic clients in New York City were randomly assigned to
      receive a four- or eight-week intervention aimed at reducing sexual risk or to
      serve as controls. Information on their HIV testing experiences was gathered
      through interviews at baseline and one month, six months and one year after the
      intervention. RESULTS: At baseline, 67% of women had been tested for HIV. The
      predominant reason for not being tested was anxiety about the result. Regardless
      of their testing status at baseline, more than 40% of the women believed that
      getting tested is a good way to prevent acquiring HIV. Women in the intervention
      who had been tested multiple times or had last been tested more than six months
      ago were more likely than women in the control group to initiate HIV testing by
      the one-month follow-up (relative risk, 2.9 and 6.1, respectively). Rates of
      mutual testing (being tested at the same time as one's partner) were
      significantly greater among women who participated in an intervention than among
      controls at the one-month and six-month interviews. CONCLUSIONS: HIV test
      counseling must emphasize that testing is not a prevention strategy in and of
      itself. Mutual testing, although not without risks, offers the safest possible
      alternative for monogamous couples who choose to forgo condoms.

PMID- 12043713
TI  - Risk of postpartum induced abortion in Finland: a register-based study.
AB  - CONTEXT: Half of Finnish abortion patients already have children, and one in 10
      pregnancies ending in abortions started within 12 months of a birth. Thus, many
      women may not practice contraception effectively during the postpartum period.
      METHODS: Data from national registers were used to create ajoint data file on
      pregnancies occurring in Finland over the period 1987-1998. The abortion risk
      (the risk of a conception that leads to an induced abortion) and abortion ratio
      (the number of conceptions leading to abortions divided by the number leading to
      deliveries) were analyzed in follow-up periods after all live births to women
      younger than 45 (684,922), using hazard regression and logistic regression.
      RESULTS: Pregnancies starting within eight months postpartum were more likely to
      end in abortion than were those starting later. Within the first eight months,
      the shorter the interval to the next pregnancy, the more likely the pregnancy was
      to end in abortion. Abortion risk was higher 6-18 months postpartum than at later
      periods and was highest at 6-8 months postpartum, particularly among unmarried
      women and teenagers. Between 1987-1988 and 1995-1996, the abortion risk within
      the first eight months postpartum rose significantly among women aged 25-29 and
      30-34 (relative risks, 1.5 and 1.2, respectively). The abortion risk and abortion
      ratio were higher among teenagers than among women in other age-groups.
      CONCLUSIONS: The findings are consistent with the hypothesis that contraceptive
      practice is less effective postpartum, suggesting room for improvement in
      postpartum contraceptive counseling in Finland.

PMID- 12043714
TI  - A model for involving youth in health planning: HIV prevention in Pennsylvania.

PMID- 12043715
TI  - The checkered history and bright future of intrauterine contraception in the
      United States.

PMID- 12043716
TI  - In-vitro susceptibility of Haemophilus influenzae to loracarbef (LY 163892) and
      other oral antibiotics. Collaborative Study Group on Pediatric Infectious Disease
      in Lombardy.
AB  - Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared
      the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other
      agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated
      from adults and children at Istituti Clinici di Perfezionamento of Milano,
      between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in
      Lombardy during 1988. In adults 72 strains were all isolated from sputum of
      patients with pneumonia or chronic bronchitis; in children 199 strains were
      isolated from conjunctiva (53% of the patients had also a concomitant respiratory
      infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal
      fluid. Minimal inhibiting concentrations (MIC) were determined by the broth
      microdilution technique. The incidence of resistance of H. influenzae to
      ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef
      (0%) and the highest for erythromycin (94% for strains isolated from children and
      97% for strains isolated from adults).

PMID- 12043717
TI  - Total anomalous pulmonary venous drainage in a dog.

PMID- 12043718
TI  - Eosinophilic meningitis in a neonate.

PMID- 12043719
TI  - Short-term physical training improves vasodilatory capacity in cardiac patients.
AB  - There have been no previous studies that clearly demonstrate the effects of
      training on the relation between exercise capacity and vasodilatory capacity in
      skeletal muscle. This study was performed to clarify the effects of short-term,
      moderate-intensity physical training on exercise tolerance and vasodilatory
      capacity in cardiac patients. We studied 21 patients after acute myocardial
      infarction, coronary artery bypass grafting, or valve replacement. Each patient
      performed symptom-limited incremental exercise tests before and after a 2-week
      training program of moderate-intensity exercise. A cycle ergometer was used for
      both the training and exercise tests. Blood pressure measurement and respiratory
      gas analysis were continuously performed during the tests. Cardiac output was
      also measured using a dye-dilution method at rest and every 2 minutes during
      incremental exercise. Reactive hyperemic calf blood flow was measured at rest.
      After the training program, the subjects attained a significant decrease in
      systemic vessel resistance and significant increases in oxygen uptake and cardiac
      output at peak exercise. Changes in reactive hyperemic calf blood flow were
      significantly correlated with the changes in cardiac output, systemic vascular
      resistance, and the kinetics of oxygen uptake during warm-up exercise. By
      improving the peripheral vasodilatory capacity in these patients, short-term,
      moderate-intensity physical training was found to improve the cardiovascular
      adaptation not only at peak exercise, but also during the onset of exercise.

PMID- 12043720
TI  - Applying HIPPA to minors.

PMID- 12043721
TI  - [Technologies used in home care services. Role of the CLSC?].

PMID- 12043722
TI  - Psychiatric patient sues for cost of bringing up child.

PMID- 12043723
TI  - Uninsured Americans are more likely to die prematurely.

PMID- 12043724
TI  - Israeli doctors warn against rubber bullets.

PMID- 12043725
TI  - High smoking rates among Aboriginal community cause financial hardship.

PMID- 12043726
TI  - Blair says science needs strong funding and public support.

PMID- 12043728
TI  - Cognitive behaviour therapy and exercise are the only effective treatments for
      chronic fatigue, says study.

PMID- 12043729
TI  - US doctors sue over "unfair" scheme for finding jobs for medical graduates.

PMID- 12043730
TI  - Getting more for their dollar: Kaiser v the NHS. Working knowledge would have
      been needed for comparison.

PMID- 12043731
TI  - Getting more for their dollar: Kaiser v the NHS. Use of OECD database has led to
      incorrect conclusions.

PMID- 12043732
TI  - Getting more for their dollar: Kaiser v the NHS. Kaiser may be model of American
      success or aberration.

PMID- 12043733
TI  - Getting more for their dollar: Kaiser v the NHS. United States is paying more and
      getting less.

PMID- 12043734
TI  - Getting more for their dollar: Kaiser v the NHS. Like should be compared with
      like.

PMID- 12043735
TI  - Getting more for their dollar: Kaiser v the NHS. Length of stay is not the
      problem.

PMID- 12043736
TI  - "Boutique medicine" in the US. Doctors are more interested in having high incomes
      than providing better health care.

PMID- 12043737
TI  - Booked inpatient admissions and hospital capacity. Variability must be managed to
      reduce waiting times and improve care.

PMID- 12043738
TI  - Being a child of donor insemination. Donor Conception Network always advises
      openness.

PMID- 12043739
TI  - Being a child of donor insemination. Consultation is in progress about whether to
      persist with donor anonymity.

PMID- 12043740
TI  - Careers in ophthalmology.

PMID- 12043741
TI  - Landing a job in a buyer's market.

PMID- 12043744
TI  - Do you trust your hospital trust?

PMID- 12043745
TI  - How overseas doctors can get a foot in the door.

PMID- 12043746
TI  - Reversal of fortune: Medicare+Choice collides with market forces.
AB  - Private health plans' participation in Medicare was envisioned as a way to save
      taxpayers money and offer Medicare beneficiaries more choices and benefits. As
      enrollment grew, there were concerns about overpayments to some private health
      plans and wide geographic variation in plan payments. The Balanced Budget Act of
      1997 (BBA) introduced significant payment changes and regulatory requirements for
      plans participating in the newly named Medicare+Choice (M+C) program. Since
      January 1999, scores of plans have reduced or ended their participation,
      disrupting coverage for more than two million seniors. While the BBA often is
      blamed for this turnabout, research by the Center for Studying Health System
      Change (HSC) indicates private market forces also played a key role in M+C's
      growing instability.

PMID- 12043747
TI  - How vulnerable is the nation's food supply? Linking food safety and food
      security.
AB  - This paper reviews the food safety regulatory apparatus in place today. It
      examines the system's strengths and vulnerabilities, particularly in light of the
      post-September 11 environment that includes the added threat of terrorism. The
      paper touches upon legislative and budgetary proposals aimed at improving food
      security, including the growing but debated interest in a single food safety
      agency.

PMID- 12043748
TI  - Ion channel are sensitive to gravity changes.
AB  - The effects of gravity on alamethicin doped planar lipid bilayers and on
      reconstituted porins of Escherichia coli outer membrane, respectively, have been
      investigated in this paper. The aim of the study was to find out whether and how
      gravity influences the highly stratified system: membrane-ion channel, in order
      to provide a novel approach to the explanation of gravity effects on living
      systems. This is necessary, as even single cells can react to gravity changes
      without having perceptive organelles. The mechanism of this detection is not
      clear yet. One possibility might be the detection of gravity by the membrane
      itself, or by the interaction of integral membrane proteins with gravity. Here we
      show for the first time that gravity directly influences the integral open state
      probability of native ion channels (porins) incorporated into planar lipid
      bilayers. Under hypergravity, especially the open state probability of porins is
      increased, whereas it is decreased in the microgravity case. The dependency is
      sigmoidal with the steepest region at 1 to 1.3 g. In the light of these
      experiments, a general effect of gravity on ion channels and membranes seems to
      be reasonable, possibly providing an explanation for several impacts of gravity
      on living systems.

PMID- 12043749
TI  - Distribution of services and supports for people with traumatic brain injury in
      rural and urban Missouri.
AB  - New paradigms of disability suggest that many variables interact to influence the
      community functioning of people with traumatic brain injury (TBI), including
      injury severity and social, psychological, and environmental factors.
      Unfortunately, the majority of TBI outcome research to date has primarily focused
      on injury severity variables (e.g., neuroradiologic findings, loss of
      consciousness, posttraumatic amnesia) to the exclusion of environmental
      variables. Limited environmental resources such as rehabilitation professionals,
      facilities, and services may be significant barriers that affect outcome for
      people with TBI, particularly for those in rural areas. Using data from Missouri,
      where 32% of the population lives in rural counties, this study researched the
      availability of rehabilitation resources for individuals with TBI, with an
      emphasis on differences between rural and urban areas. Data indicated that there
      is a scarcity of rehabilitation professionals (i.e., physiatrists, mental health
      providers, rehabilitation therapists),facilities (i.e., hospitals offering
      comprehensive rehabilitation therapies), and services (i.e., support groups) in
      rural areas of the study state. The results suggest that (1) future
      rehabilitation researchers need to evaluate the impact of accessibility to
      rehabilitation services and resources on the outcome of people with TBI and (2)
      TBI health policy administrators need to consider how to increase rehabilitation
      resources for people with TBI in rural areas, including the use of rural-based
      training programs, rural debt-forgiveness training programs, and telehealth
      systems.

PMID- 12043750
TI  - Community entry in conducting rural focus groups: process, legitimacy, and
      lessons learned.
AB  - This article explores the value of community collaboration in a qualitative study
      of diabetes. In 1999, the Appalachian Diabetes Coalition of West Virginia
      University's Prevention Research Center employed a statewide effort to conduct
      focus groups in West Virginia to elicit cultural perspectives on diabetes and its
      management. The success of this research depended on community participation at
      many levels, particularly because of the rural, often geographically isolated
      community structure of the state. The researchers' entry into small communities
      and the involvement of local residents in focus groups was possible with the
      collaboration of the West Virginia Rural Health Education Partnerships program
      and the West Virginia University Extension Service, both of which played primary
      roles as community gatekeepers in helping the research team access and involve
      rural areas. This collaboration reinforced the value of a two-tiered approach in
      enlisting local resources. These relationships resulted in beneficial outcomes to
      all partners. Researchers benefited by gaining entry to communities, and the
      community organizations benefited by gaining a better understanding of the
      diabetic population to assist in planning programs. Working with well-established
      community groups with strong community ties is crucial when gaining entry for
      research and interventions. The identification and involvement of trusted,
      accessible members of rural communities gives research local legitimacy, ensures
      adequate participation and effective data collection, and permits entry into
      remote communities.

PMID- 12043751
TI  - Strategy to increase agricultural medicine practice: an exploratory study to
      predict interest among generalists.
AB  - Across the nation, farmers, farmworkers and their families experience an
      increased risk of death, illness and disability. A major concern is to determine
      how medical education and the medical profession can realize their potential to
      benefit the agricultural community. This exploratory study was completed to
      identify factors that might predict interest in practice of agricultural medicine
      among primary care physicians. Two hundred seventy-eight Alabama primary care
      physicians, almost equally distributed as urban and rural, completed a
      questionnaire that surveyed interest in agromedicine practice, experience
      regarding 13 agromedicine topics, and other physician characteristics. Through a
      logistic regression model, interest in agromedicine practice was predicted by a
      high proportion of practice experience in smaller communities, agromedicine
      experience through personal hobby or avocation, and through professional
      literature. These three significant variables correctly predicted a moderate to
      high level of interest in agromedicine practice in 65% of the physicians in the
      study. If these results hold up with confirmatory study, the authors recommend
      that targeted efforts to produce physicians for agricultural medicine should
      prepare physicians whose backgrounds are rural and whose interests include
      agricultural and family medicine, thus predicting location and practice relevant
      to the needs of the agricultural community.

PMID- 12043752
TI  - The reported value of rural internal medicine residency electives and factors
      that influence rural career choice.
AB  - This study examines how rural electives affect medical residents' opinions about
      rural practice and which factors encourage or discourage choice of rural
      practice. Participants in a one- to two-month rural elective and a matched group
      of randomly selected nonparticipants were surveyed. Seventy percent of the
      elective participants (n = 58) and 61% of the matched nonparticipants (n = 51)
      completed the questionnaire. The groups' responses to scaled response measures
      and open-ended questions were analyzed using t , chi-square and Mann-Whitney U
      tests. A majority of participants stated that the elective was a beneficial
      experience (n = 36), and participants' interest in rural practice increased
      significantly after the elective. Elective participants were more likely than
      nonparticipants to see breadth of practice, continuity of care, quality of life
      in rural areas, and experiences with mentors as encouraging rural practice.
      Elective participation did not demonstrably increase rural career choice,
      although this finding may be attributable to small sample size. Respondents
      identified means to encourage rural practice, as well as barriers to rural
      practice: Elective participants suggested that electives may be more effective if
      they occurred earlier in medical training, lasted for longer periods of time, and
      addressed the needs of spouses or partners. Generalizability is limited by
      several factors, including small sample size and the possibility of pre-existing
      differences between elective participants and nonparticipants.

PMID- 12043753
TI  - A pilot study of oncology staff perceptions of palliative care and psycho
      oncology services in rural and community settings in Indiana.
AB  - Although there has been an increased interest in health care delivery for rural
      community populations, concerns remain regarding the lack of access to primary
      health care and specialty services (such as palliative care), particularly in
      rural areas that are medically underserved (MU). This survey was conducted to
      examine the perceptions of palliative care services in rural communities and
      toward identifying perceived barriers that interfere with accessing palliative
      care services. In conducting the study, personnel from various disciplines
      throughout the Community Cancer Care (CCC) network (the largest private provider
      of oncology services in Indiana) completed a survey that assessed their
      perceptions of the strengths and weaknesses of the available palliative care
      services in their communities. These responses, which indicate discrepancies in
      perceptions among staff within sites, suggest problems of integration of
      palliative care in given locations. Results revealed three particularly
      problematic areas: accessing pain control, accessing psychological or psychiatric
      services or both, and overcoming barriers to hospice care. Although no
      significant differences were found for any variables between MU and adequately
      medically served (AMS) areas, in general palliative care is limited and
      unintegrated into oncology care. Confusion among staff at a particular oncology
      program likely contributes to the haphazard delivery and poor integration of
      palliative care. Conclusions are tempered by important study limitations but the
      results suggest the need for programs that improve delivery of palliative care in
      rural Indiana.

PMID- 12043754
TI  - Rural-urban differences in health risks, resource use and expenditures within
      three state medicaid programs: implications for medicaid managed care.
AB  - This study uses Medicaid claims data for income-eligible enrollees in California,
      Georgia and Mississippi to compare expenditures, resource usage and health risks
      between residents of rural and urban areas of the states. Resource use is
      measured using the Resource Based Relative Value Scale (RBRVS) system for
      professional services, hospital days and outpatient facility visits; it also is
      valued at private insurance reimbursement rates for the states. Health risks are
      measured using the diagnosis-based Adjusted Clinical Group system. Resource use
      is compared on a risk-adjusted basis with the use of urban Medicaid enrollees as
      the benchmark. We find that actual expenditures for rural care users are lower
      than for urban care users. However, because the proportion of Medicaid enrollees
      who use care is higher in rural than in urban areas in all three states,
      expenditures per rural enrollee are not consistently lower. Case mix is more
      resource intensive for rural compared to urban residents in all three states.
      Although resource usage is not systematically lower overall for rural enrollees,
      on a risk-adjusted basis they tend to use less hospital resources than urban
      enrollees. Capitation rates based on historical per enrollee expenditures would
      not appear to under-reimburse managed care organizations for the care of rural as
      opposed to urban residents in the study states.

PMID- 12043755
TI  - Quality of diets consumed by older rural adults.
AB  - Older adults residing in rural communities are at risk for low dietary quality
      because of a variety of social, physical and environmental circumstances.
      Minority elders are at additional risk because of poorer health status and lower
      socioeconomic status. This study evaluated the food group intake of 130 older
      (>70 years) African American (34%), European American (36%), and Native American
      (30%) residents of two rural communities in central North Carolina. An
      interviewer-administered food frequency questionnaire was used to measure dietary
      intake. Food items were classified into food groups similar to the United States
      Department of Agriculture (USDA) Food Guide Pyramid and the National Cancer
      Institutes 5 A Day for Better Health program. None of the survey participants met
      minimum intake recommendations and most over-consumed fats, oils, sweets and
      snacks. African Americans and Native Americans consumed fewer servings of
      meats,fruits and vegetables, and fats, oils, sweets and snacks than European
      Americans. African American men consumed the fewest servings of fruits and
      vegetables of all gender/ethnic groups. Consumption of fats, oils and sweets was
      greatest among those 85 years and older and was more common among denture users.
      National strategies to educate the public about the importance of consuming a
      varied diet based on the recommendations presented in national nutrition
      education campaigns may not be reaching older adults in rural communities,
      particularly minority group members.

PMID- 12043756
TI  - Not raising a "bubble kid": farm parents' attitudes and practices regarding the
      employment, training and supervision of their children.
AB  - This article explores farm parents' attitudes and practices regarding the
      employment, training and supervision of their children among a sample of 24 farm
      couples from southeastern Washington state. The goal was to gain a greater
      understanding of parental attitudes and practices in order to devise appropriate
      and meaningful efforts to improve the safety of children and adolescents involved
      in farm work. Demographic data regarding the farm families and their farm safety
      practices were collected through a short questionnaire, and parental attitudes
      and practices regarding the employment, training and supervision of their
      children were explored through open-ended, semi-structured interviews. The
      results suggest that farm parents have developed a logical and consistent set of
      beliefs and attitudes regarding the employment, training, and supervision of
      their children that is based in part on the belief that farm work is highly
      beneficial to their children's development. Safety interventions to reduce
      childhood farm injuries will have to acknowledge farm work as important and
      beneficial for children in order to maintain legitimacy and credibility.
      Nevertheless, because farm parents' practices regarding their children's
      employment reflect cultural beliefs and values regarding children and child
      rearing, some recommended safety guidelines will be difficult to implement.

PMID- 12043757
TI  - Cervical cancer risk as a predictor of Pap smear use in rural North Carolina.
AB  - Risk for invasive cervical cancer is reported to be higher in rural areas than
      urban ones, and cervical cancer-related mortality is higher in rural women due to
      poorer utilization of preventive services and subsequent presentation at late
      stages of the disease. This cross-sectional study examined the relationship
      between prevalence of risk factors for cervical cancer and the degree of
      compliance with risk-appropriate screening guidelines for cervical cancer.
      Secondary data were analyzed for 614 women from Robeson County, NC, aged 40 and
      older, and of mainly rural and low socioeconomic status. High-risk status was
      determined by the presence of any of the following five risk factors: a history
      of more than two sexual partners, age at first sexual intercourse under 18 years,
      history of sexually transmitted disease, history of sexually transmitted disease
      in sexual partner(s), and smoking. Low-risk status was the absence of all
      factors. A high-risk participant was considered compliant if she had had at least
      three Pap smears in the 3 years prior to the interview, while a low-risk
      participant was considered compliant if she had had at least one Pap smear within
      the previous 3 years. Overall, 82% of the participants were at high risk for
      cervical cancer. However, only 41% of all participants were compliant with the
      risk-appropriate screening guidelines. Low-risk status was significantly
      associated with compliance with cervical cancer screening guidelines (adjusted OR
      = 6.7; 95% CI = 3.7 to 11.1, p = .0001). Findings in this study population
      suggest rural women at high risk for cervical cancer are less likely to be
      compliant with appropriate Pap smear screening guidelines, indicating the need to
      target educational programs.

PMID- 12043758
TI  - Disparities in mammography screening in rural areas: analysis of county
      differences in North Carolina.
AB  - The extent to which targeted mammography programs have impacted women in rural
      areas is not well defined. We investigated mammography screening rates among 843
      women age 50 and over from a population-based sample in four predominantly rural
      eastern North Carolina counties. We examined age, race, education level, county
      of residence, health insurance, and the self-reported completion of mammography
      in the past year using contingency tables and logistic regression. African
      American females aged 65 years or older had the lowest reported mammography rates
      (42%), while white females aged 50 to 64 had the highest rates (58%). Uninsured
      women and those with less education were less likely to have received a
      mammogram. Logistic regression demonstrated that age, education, and health
      insurance were significant predictors of mammography completion. A county-level
      analysis revealed that three counties had similar rates and one county had
      substantially lower rates. A higher-than-expected rate of screening-mammography
      completion among African American women was noted in one predominantly rural
      county served by a breast cancer screening program. Logistic regression analysis
      confirmed that county was a significant predictor for mammography completion. In
      separate regressions run by race, county remained a significant predictor for
      African American women but not for white women. Differences in mammography
      screening appear to persist in some predominantly rural areas and are related to
      age, race, education, and health insurance. Programs that target hard-to-reach
      women with efforts tailored specifically to their needs may be effective in
      reducing persistent racial differences.

PMID- 12043759
TI  - Are rural residents and Hispanics less satisfied with medical care? Evidence from
      the Permian Basin.
AB  - Few population-based studies of consumers' perceptions of health care quality
      have included both rural residents and Hispanics. Using data collected through a
      random-digit telephone survey of households in the Permian Basin region of west
      Texas, an area with a relatively high percentage of Mexican Americans, we tested
      for rural/urban and ethnic differences in satisfaction with medical care. The
      study had several limitations, but the findings suggest that rural residents of
      this region rate the quality of their medical care overall more negatively than
      do their urban counterparts. No ethnic differences were found when controlling
      for demographic, social, economic, and health-status characteristics. Other
      factors, including part-time employment, a lack of continuous health insurance
      coverage, and poor health status appear to have a stronger, negative relationship
      with satisfaction. The collection and reporting of more specific measures of
      interpersonal and technical quality would further enable policy-makers, managers,
      and clinicians to better serve their patient populations.

PMID- 12043760
TI  - Rural healthy people 2010: identifying rural health priorities and models for
      practice.

PMID- 12043761
TI  - Why do rural primary care physicians sell their practices?
AB  - This study evaluates why rural primary care physicians sell their practices. A
      random sample of rural primary care practices in California, Utah, Ohio, Texas,
      and Virginia were surveyed to investigate changes in ownership of the practices
      during the period 1995-1998. These five states were selected because they
      represent areas with different experiences with physician-hospital integration
      and varied rates of managed care penetration. A series of logistic regressions
      were conducted to examine the factors that led independent physicians to sell
      their practices to either nonlocal buyers, local hospitals, or local physicians.
      Findings suggest that sales to nonlocal buyers represent the majority of practice
      ownership changes. The motivations for ceding control to nonlocal buyers center
      on managed care concerns, recruitment concerns, and administrative burdens.
      Sellers were also concerned about their level of net income prior to being
      acquired. However, the preacquisition financial concerns of sellers were not
      significantly stronger than the financial concerns of practices that remained
      independent. The environmental conditions that motivate rural physicians to sell
      their practices are not expected to improve. Therefore, additional sales of rural
      primary care practices to nonlocal buyers are expected. Further research is
      necessary to determine whether this shift in control will lead to changes in the
      quality or accessibility of care.

PMID- 12043762
TI  - The operative management of displaced fractures of the proximal humerus.

PMID- 12043763
TI  - Orthopaedics, networks and computers.

PMID- 12043764
TI  - Do warming blankets increase bacterial counts in the operating field in a laminar
      flow theatre?
AB  - Patient warming systems are used routinely to prevent hypothermia under
      anaesthesia. Airflow from warming blankets may potentially influence bacterial
      counts either by pumping 'dirty air' from floor level to the operating area or by
      blowing the patients' skin cells into the operating field from airflow under the
      blanket. Using slit-air sampling we analysed the air quality within a laminar
      flow theatre at a simulated operating site. We assessed the effect of 'high
      shedding of skin' under the blanket using volunteer patients with psoriasis. We
      also simulated general theatre activity outside the laminar-flow area in order to
      determine whether the bacterial counts in the operating field were affected. No
      colonies were grown in any of the groups tested and our results suggest that the
      patient warming system does not influence bacterial counts at the operating site
      in an ultraclean air-ventilated theatre, even with patients who have high
      shedding of skin cells.

PMID- 12043765
TI  - Exsanguination of the upper limb in healthy young volunteers.
AB  - Using a scintigraphic technique based on an autologous injection of 99mTc
      labelled erythrocytes, we have evaluated the efficiency of different
      exsanguination procedures in the upper limb of ten healthy male volunteers. The
      methods were elevation alone, the use of the Esmarch bandage or a gauze bandage,
      the Pomidor roll-cuff, the squeeze method and the Urias bag. The various
      procedures gave the following median percentage reductions of blood volumes:
      elevation for 5 seconds 44%, 15 seconds 45%, 30 seconds 46%, 60 seconds 46% and 4
      minutes 42%, the Esmarch bandage 69%, a gauze bandage 63%, the Pomidor roll-cuff
      66%, the squeeze method 53%, and the Urias bag 57%. With regard to elevation
      alone no significant differences were found. All the external methods were
      significantly more effective than elevation alone. Overall, the squeeze method
      was found to be the best method of exsanguination before inflation of a
      tourniquet, because it is effective, fast, practical and inexpensive.

PMID- 12043766
TI  - Friction burns within the tibia during reaming. Are they affected by the use of a
      tourniquet?
AB  - We have carried out a prospective, randomised trial to measure the rise of
      temperature during reaming of the tibia before intramedullary nailing. We studied
      34 patients with a mean age of 35.1 years (18 to 63) and mean injury severity
      score of 10 (9 to 13). The patients were randomised into two groups: group 1
      included 18 patients whose procedure was undertaken without a tourniquet and
      group 2, 16 patients in whom a tourniquet was used. The temperature in the bone
      was measured directly by two thermocouples inserted into the cortical bone near
      the isthmus of the tibial diaphysis. Reaming was carried out to at least 1.5 mm
      above the required diameter of the nail. Blood loss was assessed by recording the
      preoperative and postoperative haemoglobin (Hb) level. The minimum clinical
      follow-up was six months. In group 1 (no tourniquet), the mean Hb dropped 2.8
      g/dl from 14.3 +/- 1.02 g/dl to 11.5 +/- 1.04 g/dl (p = 0.0001), whereas with the
      tourniquet, the mean decrease was 1.3 g/dl from 14 +/- 1 g/dl to 12.7 +/- 1.3
      g/dl (p = 0.007). This difference was not statistically significant. The mean
      initial tibial temperature was 35.6 degrees C (SD 0.6) and rose with reaming to
      levels between 36.3 degrees C and 51.6 degrees C. The highest temperatures were
      obtained with the largest reamers (11 and 12 mm, p = 0.0001) and the most rapid
      rise with the smallest diameters of medullary canal (8 or 9 mm). The rise of
      temperature was transient (20 s). We were unable to identify any effect of the
      use of a tourniquet on the temperature achieved. Reamed intramedullary tibial
      nailing induces a transient elevation of temperature which is directly related to
      the amount of reaming.

PMID- 12043767
TI  - Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone
      mineral density and clinical function after a hip fracture. A randomised study of
      63 women.
AB  - A total of 63 women who had an operation for a fracture of the hip was randomly
      allocated to one year of treatment either with anabolic steroids, vitamin D and
      calcium (anabolic group) or with calcium only (control group). The thigh muscle
      volume was measured by quantitative CT. The bone mineral density of the hip,
      femur and tibia was assessed by quantitative CT and dual-energy x-ray
      absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed
      that the anabolic group did not lose muscle volume during the first 12 months
      whereas the control group did (p<0.01). There was less bone loss in the proximal
      tibia in the anabolic group than in the control group. The speed of gait and the
      Harris hip score were significantly better in the anabolic group after six and 12
      months. Anabolic steroids, even in this moderate dose, given in combination with
      vitamin D and calcium had a beneficial effect on muscle volume, bone mineral
      density and clinical function in this group of elderly women.

PMID- 12043768
TI  - Impacted valgus fractures (B1.1) of the proximal humerus. The results of non
      operative treatment.
AB  - We present a retrospective study of 125 patients with an impacted valgus fracture
      (B1.1) of the proximal humerus. This fracture rarely occurs in young patients and
      is much more common in elderly fit subjects. All patients were documented
      prospectively and followed for one year. None was treated surgically. At one
      year, 80.6% of the patients had a good or excellent result, the quality of which
      depended on the age of the patient and the degree of displacement of the
      fracture. Mean outcome scores based on these two parameters are presented. A
      comparison with data from other studies suggests that operative fixation of these
      fractures is not necessary.

PMID- 12043769
TI  - Extracorporeal shock-wave therapy for tendonitis of the rotator cuff. A double
      blind, randomised, controlled trial.
AB  - We have performed a double-blind placebo-controlled trial of moderate doses of
      extracorporeal shock-wave therapy (ESWT) for non-calcific tendonitis of the
      rotator cuff. Adults (74) with chronic tendonitis of the rotator cuff were
      randomised to receive either active (1500 pulses ESWT at 0.12 mJ/mm2) or sham
      treatment, monthly for three months. All were assessed before each treatment, and
      at one and three months after the completion of treatment. The outcome was
      measured with regard to pain in the shoulder, including a visual analogue score
      for night pain, and a disability index. There were no significant differences
      between the two groups before treatment. The mean duration of symptoms in both
      groups was 23.3 months. Both showed significant and sustained improvements from
      two months onwards. There was no significant difference between them with respect
      to change in the Shoulder Pain and Disability Index (SPADI) scores or night pain
      over the six-month period. A mean (+/-SD; range) change in SPADI of 16.1 +/- 27.2
      (0 to 82) in the treatment group and 24.3 +/- 24.8 (-11 to 83) in the sham group
      was noted at three months. At six months the mean changes were 28.4 +/- 25.9 (-24
      to 69) and 30.4 +/- 31.2 (-12 to 88), respectively. Similar results were noted
      for night pain. We conclude that there is a significant and sustained placebo
      effect after moderate doses of ESWT in patients with non-calcific tendonitis of
      the rotator cuff, but there is no evidence of added benefit when compared with
      sham treatment.

PMID- 12043770
TI  - Resection arthroplasty of the sternoclavicular joint for the treatment of primary
      degenerative sternoclavicular arthritis.
AB  - We describe the mid-term clinical results of the surgical treatment of primary
      degenerative arthritis of the sternoclavicular joint in eight women. They had not
      responded to conservative treatment and underwent a limited resection
      arthroplasty. For pre- and postoperative clinical evaluation we used the Rockwood
      score for the sternoclavicular joint. Postoperatively, the Constant score was
      also determined. The mean follow-up was 31 months (10 to 82). The median Rockwood
      score increased from 6 to 12.5 points. The median postoperative Constant score
      was 87 (65 to 91). Four patients had an excellent, three a good, and one a poor
      result. All patients were pleased with the cosmetic result. Resection
      arthroplasty is an effective and safe treatment for chronic, symptomatic
      degenerative arthritis of the sternoclavicular joint with a high degree of
      patient satisfaction.

PMID- 12043771
TI  - Intraoperative blood loss during cervical laminoplasty correlates with the
      vertebral intraosseous pressure.
AB  - The systemic arterial pressure has been used as a guide for determining the
      susceptibility to surgical bleeding during controlled hypotensive anaesthesia.
      Arterial hypotension is not, however, necessarily accompanied by venous or
      intraosseous hypotension. The main source of bleeding during posterior spinal
      surgery is the bone and is venous rather than arterial. The intraoperative blood
      loss, the intraosseous pressure (IOP) within the first thoracic vertebral body,
      and the systemic arterial pressure were measured in 27 patients during cervical
      laminoplasty for spondylotic myelopathy. The intraoperative blood loss correlated
      significantly with the vertebral IOP (p = 0.0073, r = 0.499), but not with
      systemic arterial pressure, age, or body-weight. The systemic arterial pressure
      did not correlate with the vertebral IOP. The mean value of the mean arterial
      pressure throughout the operation varied between 74 and 110 mmHg. The findings
      suggest that the vertebral IOP parallels surgical bleeding during posterior
      spinal surgery under normotensive anaesthesia and that patients with a low
      arterial pressure do not necessarily have a low IOP.

PMID- 12043772
TI  - The surgical treatment of bony metastases of the spine and limbs.
AB  - The skeleton is the most common site to be affected by metastatic cancer. The
      place of surgical treatment and of different techniques of reconstruction has not
      been clearly defined. We have studied the rate of survival of 94 patients and the
      results of the surgical treatment of 91 metastases of the limbs and pelvis, and
      18 of the spine. Variables included the different primary tumours, the metastatic
      load at the time of operation, the surgical margin, and the different techniques
      of reconstruction. The survival rate was 0.54 at one year and 0.27 at three
      years. Absence of visceral metastases and of a pathological fracture, a time
      interval of more than three years between the diagnosis of cancer and that of the
      first skeletal metastasis, thyroid carcinoma, prostate carcinoma, renal-cell
      carcinoma, breast cancer, and plasmacytoma were positive variables with regard to
      survival. The metastatic load of the skeleton and the surgical margin were not of
      significant influence. In tumours of the limbs and pelvis, the local failure rate
      was 0% after biological reconstruction (10), 3.6% after cemented or uncemented
      osteosynthesis (28) and 1.8% after prosthetic replacement (53). The local failure
      rate after stabilisation of the spine (18) was 16.6%. There was local recurrence
      in seven patients (6.4%), and in four of these the primary tumour was a renal
      cell carcinoma. The local recurrence rate was 0% after extralesional (24) and
      8.2% after intralesional resection (85). Improvements in the oncological
      management of patients with primary and metastatic disease have resulted in an
      increased survival rate. In order to avoid additional surgery, it is essential to
      consider the expected time of survival of the reconstruction and, in bony
      metastases with a potentially poor response to radiotherapy, the surgical margin.

PMID- 12043773
TI  - Lumbar and lumbosacral tuberculous spondylodiscitis in adults. Redefining the
      indications for surgery.
AB  - We have reviewed, retrospectively, 66 adult patients who were treated for lumbar
      or lumbosacral tuberculosis. A total of 45 had a paravertebral or epidural
      abscess, 24 had clinical instability and 18 presented with a radiculopathy, of
      which six also had a motor deficit. The diagnosis was usually made on clinical
      and radiological grounds and they were followed up until there were clinical and
      radiological signs of full recovery. Conservative treatment with antituberculous
      drugs was successful in 55 patients (83%). None had persistent instability,
      radiculopathy or neurological compromise. We feel that tuberculous
      spondylodiscitis, especially in the lumbar spine, can usually be satisfactorily
      managed conservatively and that there are few indications for surgical treatment.

PMID- 12043774
TI  - Transtrochanteric valgus osteotomy for the treatment of osteoarthritis of the hip
      secondary to acetabular dysplasia.
AB  - Our study describes the mid-term clinical results of the use of transtrochanteric
      valgus osteotomy (TVO) for the treatment of osteoarthritis of the hip secondary
      to acetabular dysplasia. The operation included valgus displacement at the level
      of the lesser trochanter, and lateral displacement of the greater trochanter by
      inserting a wedge of bone. We reviewed 70 hips. The mean age of the patients at
      operation was 44 years (14 to 59). Most (90%) had advanced osteoarthritis. The
      scores for pain and gait had improved significantly at a mean follow-up of 9.4
      years. The rate of survival until an endpoint of a further operation during a
      follow-up of ten years was 82%. The survival rate was 95% in patients with
      unilateral involvement who were less than 50 years of age at operation. TVO is a
      useful form of treatment for advanced osteoarthritis of the hip, particularly in
      young patients with unilateral disease.

PMID- 12043775
TI  - Charnley low-frictional torque arthroplasty in patients under the age of 51
      years. Follow-up to 33 years.
AB  - Between November 1962 and December 1990 a group of 1092 patients, 668 women and
      424 men, under the age of 51 years at the time of surgery, underwent 1434 primary
      Charnley low-frictional torque arthroplasties and are being followed up
      indefinitely. Their mean age at operation was 41 years (12 to 51). At the latest
      review in June 2001 the mean follow-up had been for 15 years 1 month. Of the 1092
      patients 54 (66 hips) could not be traced, 124 (169 hips) were known to have died
      and 220 (248 hips) had had a revision procedure. At a mean follow-up of 17 years
      and 5 months, 759 patients (951 hips) are still attending. In this group
      satisfaction with the outcome is 96.2%. The incidence of deep infection for the
      whole group was 1.67%. It was more common in patients who had had previous
      surgery (hemi- and total hip arthroplasties excluded), 2.2% compared with 1.5% in
      those who had not had previous surgery, but this difference was not statistically
      significant (p = 0.4). There were fewer cases of deep infection if gentamicin
      containing cement was used, 0.9% compared with 1.9% in those with plain acrylic
      cement, but this was not also statistically significant (p = 0.4). There was a
      significantly higher rate of revision in patients who had had previous hip
      surgery, 24.8% compared with 14.1% in those who had not had previous surgery (p <
      0.001). At the latest review, 1.95% are known to have had at least one
      dislocation and 0.4% have had a revision for dislocation. The indication for
      revision was aseptic loosening of the cup (11.7%), aseptic loosening of the stem
      (4.9%), a fractured stem (1.7%), deep infection (1.5%) and dislocation (0.4%).
      With revision for any indication as the endpoint the survivorship was 93.7% (92.3
      to 95.0) at ten years, 84.7% (82.4 to 87.1) at 15 years, 74.3% (70.5 to 78.0) at
      20 years and 55.3% (45.5 to 65.0) at 27 years, when 55 hips remained 'at risk'.

PMID- 12043776
TI  - Revision of the femoral prosthesis with impaction allografting and a Charnley
      stem. A 2- to 12-year follow-up.
AB  - Impacted morcellised bone allograft and a Charnley stem was used to revise 59
      loose femoral components in 57 consecutive patients. Femoral bone loss was rated
      as Endo-Klinik grade 2 in nine patients, grade 3 in 41, and grade 4 in nine. The
      immediate postoperative radiographs and those taken at the most recent follow-up
      were compared for radiolucencies, subsidence and incorporation of the graft. One
      patient was lost to follow-up and two were not available for radiological
      analysis. The mean clinical follow-up in 58 procedures was 56.7 months (24 to
      144) and the mean radiological review of 56 reconstructions was 54.4 months (24
      to 144). An intraoperative femoral fracture occurred in one patient (1.7%) and
      was successfully treated by strut grafting and cerclage wiring. Extrusion of
      cement through perforations or incomplete hoop fractures was detected in the
      postoperative radiographs of ten procedures (17%); none of these patients
      sustained a complete fracture. Three patients had dislocations (5%) and two
      (3.5%) developed painful subsidence of the stem which required a further
      revision. The latest follow-up radiographs in 56 reconstructions showed a well
      fixed stem and radiological healing of the graft in 52 (93%), and definite
      loosening in four (7%). Of these four, two were revised again and two were
      asymptomatic after a follow-up of 120 months each. The mean subsidence in the 52
      successful revisions was 0.38 mm (0 to 4). Impaction allografting with a Charnley
      stem restored bone stock and provided adequate fixation of the stem in 93% of the
      hips. There was a low rate of rerevision (3.5%) and a low incidence of
      intraoperative and postoperative complications.

PMID- 12043777
TI  - The natural history and significance of radiolucent lines at a cemented femoral
      interface.
AB  - We studied 185 total hip replacements and related the identification of
      radiolucent lines (RLLs) at two years to the later development of lytic lesions
      and loosening. Linear polyethylene wear was also measured. RLLs appeared in 34
      hips at a mean of 2.0 years after operation, and lytic lesions in ten hips at 5.7
      years. Of 151 THRs without RLLs there was neither rapid migration nor loosening
      and only one developed a possible lytic lesion. Of 23 hips with non-progressive
      RLLs there was neither rapid migration nor loosening, but six developed a lytic
      lesion. By contrast, 11 THRs with progressive RLLs migrated rapidly and seven
      developed a lytic lesion. Six THRs with progressive RLLs failed. The wear rates
      were the same in all groups, although limited numbers were available for study.
      If the surgeon achieves secure initial fixation as shown by slow or no migration
      and no RLLs during the first two years, it is likely that no lytic lesions will
      develop by five years or aseptic loosening by ten years. If an imperfect, but
      adequate, interface is achieved, as shown by slow migration and non-progressive
      RLLs lytic lesions adjacent to the RLLs may develop by five years, but aseptic
      loosening will be unlikely at ten. Insecure initial fixation, as shown by more
      rapid migration and progressive RLLs at two years, is likely to lead to the
      formation of lytic lesions at five years and loosening at ten. The outcome after
      THR is therefore determined at the initial operation and may be predicted at two
      years. The presence of lytic lesions reflects soft tissue at the interface as
      shown by the RLLs which accompany and promote loosening but, in our study, did
      not cause it.

PMID- 12043778
TI  - The contour of the femoral head-neck junction as a predictor for the risk of
      anterior impingement.
AB  - Impingement by prominence at the femoral head-neck junction on the anterior
      acetabular rim may cause early osteoarthritis. Our aim was to develop a simple
      method to describe concavity at this junction, and then to test it by its ability
      to distinguish quantitatively a group of patients with clinical evidence of
      impingement from asymptomatic individuals who had normal hips on examination. MR
      scans of 39 patients with groin pain, decreased internal rotation and a positive
      impingement test were compared with those of 35 asymptomatic control subjects.
      The waist of the femoral head-neck junction was identified on tilted axial MR
      scans passing through the centre of the head. The anterior margin of the waist of
      the femoral neck was defined and measured by an angle (alpha). In addition, the
      width of the femoral head-neck junction was measured at two sites. Repeated
      measurements showed good reproducibility among four observers. The angle alpha
      averaged 74.0 degrees for the patients and 42.0 degrees for the control group (p
      < 0.001). Significant differences were also found between the patient and control
      groups for the scaled width of the femoral neck at both sites. Using standardised
      MRI, the symptomatic hips of patients who have impingement have significantly
      less concavity at the femoral head-neck junction than do normal hips. This test
      may be of value in patients with loss of internal rotation for which a cause is
      not found.

PMID- 12043779
TI  - Functional analysis of the effect of the posterior stabilising cam in two total
      knee replacements. A comparison of the Insall/Burstein and Bisurface prostheses.
AB  - The Bisurface knee prosthesis (BP) has a posterior stabilising cam (ball-and
      socket joint) in the mid-posterior region of the femorotibial joint in an attempt
      to improve the range of movement. Based on an in vitro weight-bearing study
      contact areas of the Insall/Burstein 2 (IB2) and the BP knee were compared using
      pressure-sensitive films. The stability afforded by the cam was evaluated by
      means of dislocation distances in the vertical and horizontal planes. Significant
      adverse anterior translation in mid-flexion was not observed with the BP knee
      since the cam was effective above 60 degrees of flexion. At flexion of 60 degrees
      or more, the total contact areas were larger, as the cam represented a weight
      bearing surface. The dislocation distances for the BP knee compared favourably
      with those for the IB2 knee. We conclude that the cam of the BP knee allows good
      movement, stability and wear.

PMID- 12043780
TI  - Incidence and natural history of deep-vein thrombosis after total knee
      arthroplasty. A prospective, randomised study.
AB  - We have evaluated prospectively the incidence and location of deep-vein
      thrombosis (DVT), the risk factors for pulmonary embolism, and the natural
      history of thrombosis after total knee replacement (TKR) in patients who did not
      receive prophylactic or therapeutic treatment for DVT. We studied 227 patients
      who underwent primary TKR; 116 had one-stage bilateral and 111 unilateral
      procedures. Coagulation assays, the full blood count and blood typing tests for
      the serum chemical profile were undertaken in all patients on three separate
      occasions. Bilateral simultaneous or unilateral venograms were carried out at six
      or seven days after operation. Perfusion lung scanning was undertaken before and
      at seven or eight days after operation. Bilateral simultaneous or unilateral
      venograms were repeated six months after operation in all patients who had
      thrombi. In the 116 patients with a bilateral replacement, 97 of 232 venograms
      (41.8%) were positive for fresh thrombi while there were 46 positive venograms
      (41.4%) in the 111 patients with a unilateral replacement (p = 1.000). Of the 116
      venograms in knees with a cemented replacement, 45 (38.8%) were positive for
      thrombi while 52 of the 116 venograms (44.8%) were positive in those with a
      cementless replacement (p = 0.675). Further venograms at six months after
      operation in all 143 limbs which had thrombi showed that all had completely
      resolved regardless of the size or location. No pulmonary embolism occurred as
      shown by negative perfusion lung scans and the absence of symptoms. Although the
      current prevailing opinion is that patients with thrombosis in the proximal veins
      should receive anticoagulant treatment, our study has shown that all thrombi
      regardless of their size or location resolved without causing pulmonary embolism.

PMID- 12043781
TI  - Transplantation of cartilage-like tissue made by tissue engineering in the
      treatment of cartilage defects of the knee.
AB  - We investigated the clinical, arthroscopic and biomechanical outcome of
      transplanting autologous chondrocytes, cultured in atelocollagen gel, for the
      treatment of full-thickness defects of cartilage in 28 knees (26 patients) over a
      minimum period of 25 months. Transplantation eliminated locking of the knee and
      reduced pain and swelling in all patients. The mean Lysholm score improved
      significantly. Arthroscopic assessment indicated that 26 knees (93%) had a good
      or excellent outcome. There were few adverse features, except for marked
      hypertrophy of the graft in three knees, partial detachment of the periosteum in
      three and partial ossification of the graft in one. Biomechanical tests revealed
      that the transplants had acquired a hardness similar to that of the surrounding
      cartilage. We conclude that transplanting chondrocytes in a newly-formed matrix
      of atelocollagen gel can promote restoration of the articular cartilage of the
      knee.

PMID- 12043782
TI  - An alternative to fixation of displaced fractures of the anterior intercondylar
      eminence in children.
AB  - Fractures of the anterior intercondylar eminence in children are relatively
      uncommon. There is considerable debate as to the best treatment of displaced
      fractures, but most methods described in the literature involve an open procedure
      combined with some form of fixation. Using human anatomical dissections, we have
      shown that the transverse meniscal ligament can become incarcerated within the
      fracture and act as a block to reduction. We describe an arthroscopic technique
      which requires no fixation device and report the results of its use in eight
      displaced fractures. This method gives reliable results and offers the advantage
      of less potential morbidity.

PMID- 12043783
TI  - Retroversion of the humeral head in children with an obstetric brachial plexus
      lesion.
AB  - We undertook a prospective MRI study to measure the retroversion of the humeral
      head in 33 consecutive infants with a mean age of 1 year 10 months (3 months to 7
      years 4 months) who had an obstetric brachial plexus lesion (OBPL). According to
      a standardised MRI protocol both shoulders and humeral condyles were examined and
      the shape of the glenoid and humeral retroversion determined. The mean humeral
      retroversion of the affected shoulder was significantly increased compared with
      the normal contralateral side (-28.4 +/- 12.5 degrees v -21.5 +/- 15.1 degrees, p
      = 0.02). This increase was found only in the children over the age of 12 months.
      In this group humeral retroversion was -29.9 +/- 12.9 degrees compared with -19.6
      +/- 15.6 degrees in the normal shoulder (p = 0.009), giving a mean difference of
      10.3 degrees (95% confidence interval 3.3 to 17.3). This finding is of importance
      when considering the operative treatment for subluxation of the shoulder in
      children with an OBPL.

PMID- 12043784
TI  - Limb loss following the use of heparin. A lesson to be remembered.
AB  - The optimal method of prophylaxis against venous thromboembolism after total hip
      replacement (THR) remains uncertain. Most surgeons use some form of
      pharmacological prophylaxis, most commonly heparin. The precise balance of the
      benefits and risks is unclear, and serious complications can occur. We describe a
      case of heparin-induced thrombocytopenia and thrombosis syndrome in a 62-year-old
      woman after THR.

PMID- 12043785
TI  - Meralgia paraesthetica. A complication of a patient-positioning device in total
      hip replacement.
AB  - We describe three patients who developed meralgia paraesthetica after the use of
      a well-padded and carefully-placed patient-positioning device in total hip
      replacement.

PMID- 12043786
TI  - Influence of extracorporeal shock-wave application on normal bone in an animal
      model in vivo. Scintigraphy, MRI and histopathology.
AB  - There is little information about the effects of extracorporeal shock-wave
      application (ESWA) on normal bone physiology. We have therefore investigated the
      effects of ESWA on intact distal rabbit femora in vivo. The animals received 1500
      shock-wave pulses each of different energy flux densities (EFD) on either the
      left or right femur or remained untreated. The effects were studied by bone
      scintigraphy, MRI and histopathological examination. Ten days after ESWA (0.5
      mJ/mm2 and 0.9 mJ/mm2 EFD), local blood flow and bone metabolism were decreased,
      but were increased 28 days after ESWA (0.9 mJ/mm2). One day after ESWA with 0.9
      mJ/mm2 EFD but not with 0.5 mJ/mm2, there were signs of soft-tissue oedema,
      epiperiosteal fluid and bone-marrow oedema on MRI. In addition, deposits of
      haemosiderin were found epiperiosteally and within the marrow cavity ten days
      after ESWA. We conclude that ESWA with both 0.5 mJ/mm2 and 0.9 mJ/mm2 EFD
      affected the normal bone physiology in the distal rabbit femur. Considerable
      damaging side-effects were observed with 0.9 mJ/mm2 EFD on periosteal soft tissue
      and tissue within the bone-marrow cavity.

PMID- 12043787
TI  - The temporal sequence of spontaneous repair of osteochondral defects in the knees
      of rabbits is dependent on the geometry of the defect.
AB  - Damage to articular cartilage is a common injury, for which there is no effective
      treatment. Our aims were to investigate the temporal sequence of the repair of
      articular cartilage and to define a critical-size defect. Full-thickness defects
      were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of
      the defects was varied in order to determine the effect that the size and depth
      of the defect had on its healing. The defects were made in the femoral groove of
      the knee with one defect per knee and eight knees per group. The tissues were
      fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and
      the sections stained with Toluidine Blue. These were then examined and evaluated
      for several parameters including the degree of metachromasia and the amount of
      subchondral bone which had reformed in the defect. The defects had a
      characteristic pattern of healing which differed at different days and for
      different sizes of defect. Specifically, the defects of 1 mm first peaked in
      terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of
      3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1
      mm.

PMID- 12043788
TI  - The shapes of the tibial and femoral articular surfaces in relation to
      tibiofemoral movement.
AB  - We report a study of the shapes of the tibial and femoral articular surfaces in
      sagittal, frontal and coronal planes which was performed on cadaver knees using
      two techniques, MRI and computer interpolation of sections of the articular
      surfaces acquired by a three-dimensional digitiser. The findings using MRI,
      confirmed in a previous study by dissection, were the same as those using the
      digitiser. Thus both methods appear to be valid anatomical tools. The tibial and
      femoral articular surfaces can be divided into anterior segments, contacting from
      0 degrees to 20 +/- 10 degrees of flexion, and posterior segments, contacting
      from 20 +/- 10 degrees to 120 degrees of flexion. The medial and lateral
      compartments are asymmetrical, particularly anteriorly. Posteromedially, the
      femur is spherical and is located in a conforming, but partly deficient, tibial
      socket. Posterolaterally, it is circular only in the sagittal section and the
      tibia is flat centrally, sloping downwards both anteriorly and posteriorly to
      receive the meniscal horns. Anteromedially, the femur is convex with a sagittal
      radius larger than that posteriorly, while the tibia is flat sloping upwards and
      forwards. Anterolaterally, both the femoral and tibial surfaces are largely
      deficient. These shapes suggest that medially the femur can rotate on the tibia
      through three axes intersecting in the middle of the femoral sphere, but that the
      sphere can only translate anteroposteriorly and even then to a limited extent.
      Laterally, the femur can freely translate anteroposteriorly, but can only rotate
      around a transverse axis for that part of the arc, i.e., near extension, during
      which it comes into contact with the tibia through its flattened distal/medial
      surface as against its spherical posterior surface.

PMID- 12043789
TI  - Lack of correlation between different measurements of proprioception in the knee.
AB  - Current methods of measurement of proprioceptive function depend on the ability
      to detect passive movement (kinaesthesia) or the awareness of joint position
      (joint position sense, JPS). However, reports of proprioceptive function in
      healthy and pathological joints are quite variable, which may be due to the
      different methods used. We have compared the validity of several frequently used
      methods to quantify proprioception. Thirty healthy subjects aged between 24 and
      72 years underwent five established tests of proprioception. Two tests were used
      for the measurement of kinaesthesia (KT1 and KT2). Three tests were used for the
      measurement of JPS, a passive reproduction test (JPS1), a relative reproduction
      test (JPS2) and a visual estimation test (JPS3). There was no correlation between
      the tests for kinaesthesia and JPS or between the different JPS tests. There was,
      however, a significant correlation between the tests for kinaesthesia (r = 0.86).
      We conclude therefore that a subject with a given result in one test will not
      automatically obtain a similar result in another test for proprioception. Since
      they describe different functional proprioceptive attributes, proprioceptive
      ability cannot be inferred from independent tests of either kinaesthesia or JPS.

PMID- 12043790
TI  - Low-energy extracorporeal shock-wave treatment (ESWT) for tendinitis of the
      supraspinatus.

PMID- 12043791
TI  - All-polyethylene versus metal-backed and stemmed tibial components in cemented
      total hip arthroplasty.

PMID- 12043792
TI  - Acute rupture of tendo Achillis.

PMID- 12043793
TI  - Acute rupture of tendo Achillis.

PMID- 12043794
TI  - Fuzzy rules to predict degree of malignancy in brain glioma.
AB  - The current pre-operative assessment of the degree of malignancy in brain glioma
      is based on magnetic resonance imaging (MRI) findings and clinical data. 280
      cases were studied, of which 111 were high-grade malignancies and 169 were low
      grade, so that regular and interpretable patterns of the relationships between
      glioma MRI features and the degree of malignancy could be acquired. However, as
      uncertainties in the data and missing values existed, a fuzzy rule extraction
      algorithm based on a fuzzy min-max neural network (FMMNN) was used. The
      performance of a multi-layer perceptron network (MLP) trained with the error back
      propagation algorithm (BP), the decision tree algorithm ID3, nearest neighbour
      and the original fuzzy min-max neural network were also evaluated. The results
      showed that two fuzzy decision rules on only six features achieved an accuracy of
      84.6% (89.9% for low-grade and 76.6% for high-grade cases). Investigations with
      the proposed algorithm revealed that age, mass effect, oedema, postcontrast
      enhancement, blood supply, calcification, haemorrhage and the signal intensity of
      the T1-weighted image were important diagnostic factors.

PMID- 12043795
TI  - Model-based technique for the measurement of skin thickness in mammography.
AB  - A model-based method is proposed for the measurement of breast skin thickness
      from digitised mammograms that takes into account both the geometric and
      radiographic properties of the skin region. The method initially identifies a
      salient feature that discriminates the skin from the other anatomical structures
      of the breast. Its identification is based on a multi-scale grey-level gradient
      estimation, using a wavelet decomposition of the image. The spatial distribution
      of this feature is organised as a graph, with each of its nodes associated with a
      binary set of interpretation labels. A Markov random field is defined on the set
      of labels, and the best graph labelling is finally determined with a maximum a
      posteriori (MAP) probability criterion. The method was applied on 11 mammograms
      with improved contrast characteristics at the breast periphery, obtained by an
      exposure equalisation technique during image acquisition. The validation of the
      approach was performed by calculating the root mean square (RMS) error between
      the detected skin thickness and manual measurements performed on each of the
      films. The resulting error values ranged from 0.1 mm to 0.2 mm for normal cases
      and reached a maximum of 0.5mm in pathological cases with advanced skin
      thickening.

PMID- 12043796
TI  - Novel ultrasonic fusion imaging method based on cyclic variation in myocardial
      backscatter.
AB  - Quantitative ultrasonic tissue characterisation of the myocardium based on
      integrated backscatter (IB) has the potential of becoming an effective method for
      detecting and evaluating myocardial ischaemia. To facilitate IB-based clinical
      applications, a new imaging method has been developed that combines the
      anatomical information of a B-mode image with the contractile performance of a
      selected myocardial region. To produce such a fusion image, a region of interest
      (ROI) in a B-mode cardiac image was first selected by the user. Algorithms for
      detection of the endocardium and epicardium were developed, and the resulting
      mean distance between the computer-detected curve and the manually traced curve
      was 0.83mm for the endocardium and 0.58mm for the epicardium. The cyclic
      variation of IB (CVIB) of each myocardial tissue element within the ROI was then
      calculated over one cardiac cycle. Finally, a grey-scale B-mode image at the end
      of diastole was displayed as a still image, and the pixels representing the
      myocardial tissue in the ROI colour-coded according to the corresponding CVIB
      over the past heart cycle. Both the B-mode image and the colour-coded region were
      refreshed (up-dated) at the next end-of-diastole. Preliminary results from normal
      (CVIB= 10-12dB) and ischaemic (CVIB = 5-7 dB) canine hearts are presented that
      demonstrate the utility of this new imaging method.

PMID- 12043797
TI  - Ultrasound image matching using genetic algorithms.
AB  - Image compounding reduces the artifacts inherent in ultrasound imaging, but
      accurate matching of images for compounding depends on their accurate placement
      in the compound image plane. A method is presented to reduce displacement errors
      during compounding of ultrasound B-scans of a normal human shank. A genetic
      algorithm was used to place matching B-scans in the compound image. The method
      was tested on a phantom and was shown to reduce, but not eliminate, mismatches
      due to the displacement of B-scans from their original position in the compound
      image plane. The results can be extended to applications in lower-limb
      prosthetics, where ultrasound imaging can be used to visualise the internal
      geometry of amputees' residual limbs.

PMID- 12043798
TI  - Ambulatory measurement of upper limb usage and mobility-related activities during
      normal daily life with an upper limb-activity monitor: a feasibility study.
AB  - The aim of this research was to assess the ability of an upper limb-activity
      monitor (ULAM) to discriminate between upper limb usage and non-usage in healthy
      and disabled subjects during normal daily life. The ULAM was based on ambulatory
      accelerometry and consisted of several acceleration sensors connected to a small
      recorder worn around the waist. While wearing this ULAM, four healthy and four
      disabled subjects performed an activity protocol representing normal daily life
      upper limb usage or non-usage. The motility feature (derived from the raw
      acceleration signals) was used as a measure of the extent of upper limb usage.
      Agreement scores between ULAM output and videotape recordings (reference method)
      were calculated. ULAM data that were of special interest for rehabilitation were
      detected satisfactorily (overall agreement 83.9%). There were no systematic
      differences in the agreement percentages between healthy and disabled subjects
      for mobility-related activities (p = 0.345) and the different forms of upper limb
      usage or non-usage (p= 0.715). The ULAM can be used in future studies in subjects
      with upper limb disorders to discriminate between upper limb usage and non-usage
      during performance of mobility-related activities to determine activity
      limitations.

PMID- 12043799
TI  - Biomechanical comparison of isokinetic lifting and free lifting when applied to
      chronic low back pain rehabilitation.
AB  - The study compares free and isokinetic lifting using a multivariate statistical
      analysis. Each of the 13 male subjects performed three free lifts and three
      isokinetic lifts using a CYBEX LIFTASK. The measurement variables were obtained
      from a 3D video system, two force plates and two strain-gauge transducers.
      Coupling of fuzzy space-time windowing and multiple correspondence analysis was
      used to show the links between the variables and the differences between the
      experimental situations. Isokinetic lifting had almost no points in common with
      free-lifting, but there was a similar range of extension for the different
      joints. Most free-lifting strategies could not be used in isokinetic lifting, as
      constraints between the subject and his environment were different. The main
      drawback of the isokinetic lifting was due to the necessity for individuals to
      reach the machine speed, yielding high transient efforts. The maximum vertical
      effort at the L5/S1 joint was about 1600, 1500 and 1400N for low, medium and high
      speed, whereas it was lower than 1300N, irrespective of the load, during free
      lifting. In the context of chronic low back pain rehabilitation, movement
      strategies used in free lifting could not be relearnt using an isokinetic
      machine. A better understanding of the common points and differences between
      isokinetic movement and free movement could help rehabilitation physicians to
      plan rehabilitation programmes, taking advantage of each kind of movement.

PMID- 12043800
TI  - Dynamic simulation of the natural and replaced human ankle joint.
AB  - Disappointing results for total ankle replacement have been explained by poor
      knowledge of the mechanics of the intact and replaced joints. Dynamic simulation
      tools have the capacity to simulate dynamic conditions that occur in human
      joints. The Working Model 2D tool was used to simulate the mechanics of the
      intact and replaced ankle joints, based on previously validated mathematical
      models. Elementary objects were used to model ligaments, articular surfaces,
      retinacula and muscle-tendon units. The performance of several pairs of
      prosthetic articular surfaces was also analysed. According to the results of
      these simulations, rolling as well as sliding motion occurs in the natural ankle,
      governed by a ligamentous linkage. Elongation of the tibiocalcaneal and
      calcaneofibular ligaments was found to be 1.5% and 4.8%, respectively. A 13%
      change in lever arm length occurred for both the tibialis anterior and
      gastrocnemius muscles during ankle flexion. Unlike the currently available three
      component designs, the newly proposed convex-tibial ligament-compatible
      prosthesis was found to be able to restore the original mobility and
      physiological function of the ligaments. This prosthesis combines freedom from
      restraint with congruity of the components throughout the range of flexion.

PMID- 12043801
TI  - Root canal length measurement in teeth with electrolyte compensation.
AB  - Electronic root canal length measurement devices have made it easier and faster
      to measure the root canal length of a tooth compared with the conventional
      radiographic method. Of these electronic apex locators, the frequency-dependent
      type features greater accuracy and convenience in operation. However, its
      accuracy is still influenced by the presence of blood and/or the various
      electrolytes used in root canal therapy. This study describes the development of
      a new frequency-dependent electronic apex locator featuring electrolyte
      compensation, utilising an impedance ratio and voltage difference technique to
      minimise the influence of electrolytes on the accuracy of root canal length
      measurement. The errors for distances from file tips to apical constrictions were
      determined in vivo with the device operating with electrolyte compensation. The
      measured lengths were compared with the true lengths of the extracted teeth
      determined using a microscope. The mean error was +0.14+/-0.27mm, and 95.2% of
      the measurements were within the clinical tolerance of +/-0.5mm. It was also
      found that the degree of accuracy was not dependent on the size of the apical
      foramen (p = 0.74).

PMID- 12043802
TI  - Estimation of pulmonary arterial pressure by a neural network analysis using
      features based on time-frequency representations of the second heart sound.
AB  - The objective of the study was to develop a non-invasive method for the
      estimation of pulmonary arterial pressure (PAP) using a neural network (NN) and
      features extracted from the second heart sound (S2). To obtain the information
      required to train and test the NN, an animal model of pulmonary hypertension
      (PHT) was developed, and nine pigs were investigated. During the experiments, the
      electrocardiogram, phonocardiogram and PAP were recorded. Subsequently, between
      15 and 50 S2 heart sounds were isolated for each PAP stage and for each animal
      studied. A Coiflet wavelet decomposition and a pseudo smoothed Wigner-Ville
      distribution were used to extract features from the S2 sounds and train a one
      hidden-layer NN using two-thirds of the data. The NN performance was tested on
      the remaining one-third of the data. NN estimates of the systolic and mean PAPs
      were obtained for each S2 and then ensemble averaged over the 15-50 S2 sounds
      selected for each PAP stage. The standard errors between the mean and systolic
      PAPs estimated by the NN and those measured with a catheter were 6.0 mmHg and 8.4
      mmHg, respectively, and the correlation coefficients were 0.89 and 0.86,
      respectively. The classification accuracy, using 23 mmHg mean PAP and 30 mmHg
      systolic PAP thresholds between normal PAP and PHT, was 97% and 91%,
      respectively.

PMID- 12043803
TI  - Detection of atrial-flutter and atrial-fibrillation waveforms by fetal
      magnetocardiogram.
AB  - Two cases of fetal tachycardia are reported: atrial flutter and fibrillation. The
      waveforms from each case were detected by fetal magnetocardiograms (FMCGs) using
      a 64-channel superconducting quantum interference device (SQUID) system. Because
      the magnitude of supraventricular arrhythmia signals is very weak, two
      subtraction methods were used to detect the fetal MCG waveforms: subtraction of
      the maternal MCG signal, and subtraction of the fetal ORS complex signal. It was
      found that atrial-flutter waveforms showed a cyclic pattern and that atrial
      fibrillation waveforms showed f-waves with a random atrial rhythm. Fast Fourier
      transform analysis determined the main frequency of the atrial flutter to be
      about 7Hz, and the frequency distribution of atrial fibrillation consisted of
      small, broad peaks. To visualise the current pattern, current-arrow maps, which
      simplify the observation of pseudo-current patterns in fetal hearts, of the
      averaged atrial flutter and fibrillation waveforms were produced. The map of the
      atrial flutter had a circular pattern, indicating a re-entry circuit, and the map
      of the atrial fibrillation indicated one wavelet, which was produced by a micro
      re-entry circuit. It is thus concluded that an FMCG can detect supraventricular
      arrhythmia, which can be characterised by re-entry circuits, in fetuses.

PMID- 12043804
TI  - Experimental and numerical study of the colour appearance of tattoo models.
AB  - The colour of tattooed skin has been predicted by a Monte Carlo method based on
      the optical coefficient spectra of the skin and tattoo dyes. Slices of pig skin,
      a tattoo phantom and skin phantoms with different thickness were prepared, and
      their reflectance and transmittance spectra were measured using an integrating
      sphere at wavelengths varying from 400nm to 700nm. The absorption and scattering
      coefficient spectra of skin phantoms, pig skins and the tattoo phantom were each
      calculated using the inverse Monte Carlo method. The skin phantoms and pig skins
      were overlaid on the tattoo phantom, and the reflectance spectra of the two
      layered structures were measured. The reflectance spectra of the two-layered
      structures were calculated from the optical coefficient spectra using the Monte
      Carlo method. They agreed well with the measured spectra. The colour differences
      between the calculated and measured spectra were also evaluated by the L*a*b*
      colour space distances and showed good agreement, with 3.49 for the skin phantoms
      and 8.27 for the pig skins.

PMID- 12043805
TI  - Analysis of cardiac left-ventricular volume based on time warping averaging.
AB  - The cardiac left-ventricular (LV) volume signal, obtained by acoustic
      quantification, is affected by noise and respiratory modulation, resulting in a
      large beat-to-beat variability that affects the computation of LV function
      indices. A new method is proposed to improve the evaluation of LV indices by
      applying a signal averaging technique based on dynamic time warping to
      consecutive LV volume waveforms. Volume signals obtained from ten normal young
      (NY) subjects (mean age +/- SD: 25+/-5 years) were used to evaluate the
      performance of this algorithm. To evaluate its clinical utility, the effects of
      ageing and pharmacologically induced changes on LV function were assessed by
      studying, respectively, ten normal (N) adult subjects (age 64+/-8 years) and ten
      patients with dilated cardiomyopathy during a control and low-dose dobutamine (10
      microg kg(-1) min(-1)) study. Indices of LV function were highly consistent, with
      a variability of less than 8%, even when only 16 beats were averaged,
      independently of their selection inside the whole recording. When compared with
      beat-to-beat measures, the averaging of 16 beats significantly reduced (by more
      than 50%) the interbeat variability of all indexes. Expected alterations in both
      diastolic and systolic function were evidenced both with ageing (peak filling
      atrial contraction and ejection rates: from 275+/-77 mls(-1), 76+/-30 ml s(-1)
      230+/-70 mls(-1), respectively, in NY, to 160+/-33 mls(-1), 125+/-39 mls(-1),
      163+/-54 mls(-1) in N) and with dobutamine (peak filling and ejection rates from
      160+/-72 mls(-1) and 183+/-86 mls(-1) respectively, in control, to 253+/-75 mls(
      1) and 251+/-105 mls(-1) with dobutamine). Signal averaging with time warping
      allows fast and improved assessment of LV function.

PMID- 12043806
TI  - Non-invasive Wedensky modulation within the QRS complex.
AB  - To investigate non-invasively induced Wedensky modulation, 2ms pulses of 5, 20
      and 40mA were delivered between precordial and subscapular patches synchronously
      with the ORS complex. Wavelet vector magnitude was obtained for averaged
      modulated and non-modulated complexes. The surface area of a 3D-envelope of their
      difference (WSR) was compared in 59 patients with an uncomplicated follow-up
      after myocardial infarction (MI) (42 men, 64.3+/-9.1 years), in 30 patients with
      ischaemic heart disease and a history of ventricular tachycardia/fibrillation
      (VT/VF) (29 men, 63.1+/-9.8 years), and in 53 healthy subjects (control) (22 men,
      56.6+/-10.1 years). Reproducibility of the assessment was tested by computing
      relative errors in a sub-population of 30 VT/VF patients and 47 controls.
      Wedensky modulation parameters differed significantly between control, MI and
      VT/VF subjects. In 10 ms post-modulation windows, the following WSR values were
      obtained: controls: 1184+/-496 (5mA), 1553+/-838 (20 mA) and 2092+/-1488 (40 mA);
      VT/VF: 861+/-412 (5mA), 1134+/-636 (20 mA) and 1320+/-1036 (40 mA); MI: 1305+/
      885 (5mA) and 1779+/-1169 (20 mA). With all modulating energies used, the VT/VF
      patients differed significantly from both the controls and MI patients; control
      patients against VT/VF patients: p<0.004 (5 mA), p<0.01 (20 mA) and p<0.001 (40
      mA); VT/VF patients against MI patients: p<0.02 (5mA), p<0.01 (20 mA); control
      patients against MI patients: all p=NS. The reproducibility assessment showed an
      acceptable stability of Wedensky modulation parameters. This study demonstrated
      that wavelet decomposition detects non-invasive Wedensky modulation within the
      QRS complex, and VT/VF patients are less sensitive to Wedensky modulation than
      control and MI patients.

PMID- 12043807
TI  - Joint symbolic dynamic analysis of beat-to-beat interactions of heart rate and
      systolic blood pressure in normal pregnancy.
AB  - Pregnancy induces important changes in the autonomic control. Measures of heart
      rate (HR) variability and systolic blood pressure (SP) variability are sensitive
      to those changes. The interactions between HR and SP are complex and strongly non
      linear. Therefore they cannot be completely described by linear analysis
      techniques. A study of joint symbolic dynamics is presented as a new short-term
      non-linear analysis method to investigate the interactions between HR and SP.
      Continuous, non-invasive 30 min blood pressure recordings (Portapres) of 25
      pregnant and 14 non-pregnant women were analysed. Time series of beat-to-beat HR
      and SP were extracted. Using the concept of joint symbolic dynamics, HR and SP
      changes were transformed into a bivariate symbol vector. Subsequently, this
      symbol vector was transformed into a word series (words consisting of three
      successive symbols), and the probability of occurrence of each word type was
      calculated and compared between both groups. Significant differences were found
      in five word types between pregnant and non-pregnant women: w0,4(0.021+/-0.011
      against 0.008+/-0.006; p = 0.022), w4,6(0.020+/-0.010 against 0.007+/-0.003; p =
      0.001), w3,2(0.004+/-0.003 against 0.007+/-0.003; p = 0.038), W6,5(0.009+/-0.007
      against 0.023+/-0.008; p< 0.001) and w3,6(0.011+/-0.007 against 0.023+/-0.008; p
      = 0.001). Joint symbolic dynamics provides an efficient non-linear representation
      of HR and SP interactions that offers simple physiological interpretations.

PMID- 12043808
TI  - Unconstrained and non-invasive measurement of heart-beat and respiration periods
      using a phonocardiographic sensor.
AB  - With the rapid growth in the number of elderly people in the population, interest
      in health monitoring is increasing. Therefore the development of an unconstrained
      and non-invasive vital signs measurement system could be important for monitoring
      health status at home or in hospitals or nursing facilities. A simple system is
      proposed for measuring heart-beat and respiration periods for home healthcare.
      This was achieved with a phonocardiographic (PCG) sensor set on a water-mat or
      air-mat. The PCG sensor was an acceleration sensor that extracted the vibration
      of the mat caused by heart-beat and respiration. By calculating an
      autocorrelation function of the fully rectified sensor output or by local pattern
      matching between the rectified output and a reference signal (pre-memorised for
      each subject), the system measured the average and instantaneous periods of both
      heart-beat and respiration. Results showed that these periods were measured to a
      similar level of accuracy as for the electrocardiogram and thermistor respiration
      pickup. The comparative accuracies were within the following ranges: average
      heartbeat 0.19% to 0.67%, instantaneous heartbeat 0.53% to 1.15%, average
      respiration 0.51% to 2.17%, and instantaneous respiration 2.51% to 5.20%.

PMID- 12043809
TI  - Motor unit conduction velocity distribution estimation: assessment of two short
      term processing methods.
AB  - Muscle fibre conduction velocity (MFCV) can be used as an index of the structural
      and/or functional modifications that can occur during fatigue or pathological
      processes. Current evaluation of MFCV from surface electromyography (SEMG)
      classically produces an average value. However, a single mean value is not
      sufficient when modifications affect only a small part of the conduction velocity
      distribution. In such a case, an estimation of the whole motor unit conduction
      velocity distribution (MUCV) would be advantageous. The aim of this study was the
      evaluation of the quality of two short-term methods based on cross-correlation
      (CC) and peak-to-peak (PP) estimation. A comprehensive simulation program was
      used to generate signals with known MUCV distributions. The Dmax statistic of
      Kolmogorov-Smirnov was used as an error criterion to quantify the estimation
      error and to optimise the MUCV distribution computation algorithms. The minimum
      error was observed for an analysing window of 10ms for PP and 15ms for CC. Dmax
      was significantly lower for PP (0.195+/-0.054) than for CC (0.343+/-0.073).
      Various simulations showed the strong effect of the variance of the true
      distribution on the features of the estimated ones. Clinical data measured on the
      abductor pollicis brevis were studied. MUCV was estimated on a healthy subject
      (3.63+/-0.87ms(-1)), a patient suffering from a myopathy (2.73+/-0.51ms(-1)) and
      one suffering from a neuropathy (4.38+/-0.23ms(-1)). The results demonstrate the
      overall superiority of a peak-to-peak approach.

PMID- 12043810
TI  - Effect of signal length on the performance of independent component analysis when
      extracting the lambda wave.
AB  - The aim of the study was to investigate the effect of signal length on the
      performance of a signal source separation method, independent component analysis
      (ICA), when extracting the visual evoked potential (EP) lambda wave from saccade
      related electro-encephalogram (EEG) waveforms. A method was devised that enabled
      the effective length of the recorded EEG traces to be increased prior to
      processing by ICA. This involved abutting EEG traces from an appropriate number
      of successive trials (a trial was a set of waveforms recorded from 64 electrode
      locations in a study investigating saccade performance). ICA was applied to the
      saccade-related EEG and electro-oculogram (EOG) waveforms recorded from the
      electrode locations. One spatial and five temporal features of the lambda wave
      were monitored to assess the performance of ICA applied to both abutted and non
      abutted waveforms. ICA applied to abutted trials managed to extract all six
      features across all seven subjects included in the study. This was not the case
      when ICA was applied to the non-abutted trials. It was quantitatively
      demonstrated that the process of abutting EEG waveforms was useful for ICA
      preprocessing when extracting lambda waves.

PMID- 12043811
TI  - Temperature increases associated with polymerization of irradiated PAG
      dosimeters.
AB  - Polyacrylamide gel (PAG) dosimeters show considerable promise as three
      dimensional dosimeters for the verification of complex dose distributions
      associated with conformal therapy. However, the potential of PAG dosimeters has
      not yet been borne out in clinical practice and it is apparent that basic
      investigations of these dosimeters are still required. The polymerization
      reactions in PAG dosimeters are exothermic and the heat given off by the
      reactions may influence polymerization reaction kinetics. We report the results
      of in situ measurements of local temperature increases in irradiated PAG
      resulting from heat generated by the radiation-induced exothermic polymerization
      reactions. Temperature changes proportional to the absorbed dose were observed in
      the irradiated gels, reaching a maximum of 12 degrees C under high-dose
      conditions, depending on the thermal boundary conditions. This has practical
      implications, for example, using small vials of PAG to calibrate large phantoms
      may not be appropriate since temperature differences during irradiation between
      the calibration vials and phantom may alter the morphology and quantity of the
      polymer formed, even when irradiated to the same dose. The inhibition of
      radiation-induced polymerization associated with low-level oxygen contamination
      is manifested by a delay in the onset of temperature rise during irradiation. The
      observed temperature changes are used to estimate the percentage conversion of
      double bonds from the bis/acrylamide monomers by polymerization reactions.

PMID- 12043812
TI  - Ultrasound evaluation of polymer gel dosimeters.
AB  - A new method for the evaluation of radiotherapy 3D polymer gel dosimeters has
      been developed using ultrasound to assess the significant structural changes that
      occur following irradiation of the dosimeters. The ultrasonic parameters of
      acoustic speed of propagation, attenuation and transmitted signal intensity were
      measured as a function of absorbed radiation dose. The dose sensitivities for
      each parameter were determined as 1.8 x 10(-4) s m(-1) Gy(-1), 3.9 dB m(-1) Gy(
      1) and 3.2 V(-1) Gy(-1) respectively. All parameters displayed a strong variation
      with absorbed dose that continued beyond absorbed doses of 15 Gy. The ultrasonic
      measurements demonstrated a significantly larger dynamic range in dose response
      curves than that achieved with previously published magnetic resonance imaging
      (MRI) dose response data. It is concluded that ultrasound shows great potential
      as a technique for the evaluation of polymer gel dosimeters.

PMID- 12043813
TI  - A comparison of MCNP4C electron transport with ITS 3.0 and experiment at incident
      energies between 100 keV and 20 MeV: influence of voxel size, substeps and energy
      indexing algorithm.
AB  - The condensed-history electron transport algorithms in the Monte Carlo code
      MCNP4C are derived from ITS 3.0, which is a well-validated code for coupled
      electron-photon simulations. This, combined with its user-friendliness and
      versatility, makes MCNP4C a promising code for medical physics applications. Such
      applications, however, require a high degree of accuracy. In this work, MCNP4C
      electron depth-dose distributions in water are compared with published ITS 3.0
      results. The influences of voxel size, substeps and choice of electron energy
      indexing algorithm are investigated at incident energies between 100 keV and 20
      MeV. Furthermore, previously published dose measurements for seven beta emitters
      are simulated. Since MCNP4C does not allow tally segmentation with the *F8 energy
      deposition tally, even a homogeneous phantom must be subdivided in cells to
      calculate the distribution of dose. The repeated interruption of the electron
      tracks at the cell boundaries significantly affects the electron transport. An
      electron track length estimator of absorbed dose is described which allows tally
      segmentation. In combination with the ITS electron energy indexing algorithm,
      this estimator appears to reproduce ITS 3.0 and experimental results well. If,
      however, cell boundaries are used instead of segments, or if the MCNP indexing
      algorithm is applied, the agreement is considerably worse.

PMID- 12043814
TI  - Tolerance levels for quality assurance of electron density values generated from
      CT in radiotherapy treatment planning.
AB  - Methods are described which relate the uncertainty in relative electron density
      derived from CT numbers to the uncertainty in treatment plan calculation for both
      photon and electron beams. These relationships are used to generate tolerance
      levels for electron density quality assurance measurements. These tolerance
      levels are dependent on treatment beam energy and tissue thickness, and are
      generally broader than current recommendations. The predicted treatment plan
      errors associated with these tolerance levels are shown to be consistent with
      calculations made using two commercial treatment planning systems. The tolerance
      levels are also shown to be practical by comparison against quality assurance
      measurements made on a conventional CT scanner and a treatment simulator CT
      system over a 12-month period. The results demonstrate that broader tolerances
      than are currently recommended can be justified in all situations except for
      electron beam treatments in which the therapeutic range falls within lung tissue.

PMID- 12043815
TI  - A theoretical model for prescription of the patient-specific therapeutic activity
      for radioiodine therapy of Graves' disease.
AB  - A fundamental function of the thyroid is to extract iodine from the blood,
      synthesize it into thyroid hormones, and release it into the circulation under
      feedback control by pituitary-secreted hormones. This capability of the thyroid,
      termed as functionality, can in principle be related to the severity of
      hyperthyroidism in individual patients. In this paper the uptake and release of
      131I by the thyroid following the administration of 131I therapy for Graves'
      disease has been theoretically studied. The kinetics of iodine in the thyroid and
      blood have been evaluated using a two-compartment model. This simplified model
      appears to be adequate for dosimetry purposes and allows one to correlate levels
      of increased thyroid functionality (hyperthyroidism) with clinically measurable
      kinetic parameters. An expression has been derived for the rate of change of
      thyroid mass following therapy; this has the same form as an empirical
      relationship described in an earlier work. A method is presented for calculation
      of the amount of radioiodine activity to be administered to individual patients
      in order to achieve the desired final functionality of the gland. The activity to
      be administered is based on measurements of 131I kinetics after the
      administration of a 'low-activity' (1850 kBq) tracer for treatment planning.

PMID- 12043816
TI  - Some present problems and a proposed experimental phantom for SAR compliance
      testing of cellular telephones at 835 and 1900 MHz.
AB  - This paper compares the maximum allowable powers of some typical cellular
      telephones at 835 and 1900 MHz for compliance with the limits of specific
      absorption rates (SAR) given in ANSI/IEEE, ICNIRP and the proposed modification
      of ANSI/IEEE safety guidelines. It is shown that the present ANSI/IEEE guideline
      is the most conservative with the ICNIRP guidelines allowing a maximum radiated
      powerthat is 2.5-3 times higher, and the proposed IEEE modification of treating
      pinna as an extremity tissue the least conservative allowing even higher radiated
      powers by up to 50%. The paper also expands the previously reported study of
      energy deposition in models of adults versus children to two different and
      distinct anatomically-based models of the adult head, namely the Utah model and
      the 'Visible Man' model, each of which is increased or reduced by the voxel size
      to obtain additional head models larger or smaller in all dimensions by 11.1% or 
      9.1%, respectively. The peak 1 g body-tissue SAR calculated using the widely
      accepted FDTD method for smaller models is up to 56% higher at 1900 MHz and up to
      20% higher at 835 MHz compared to the larger models, with the average models
      giving intermediate SARs. Also given in the paper is a comparison of the peak 1 g
      and 10 g SARs for two different anatomically-based models with 6 mm thick smooth
      plastic ear models used for SAR compliance testing. The SARs obtained with the
      insulating plastic ear models are up to two or more times smaller than realistic
      anatomic models. We propose a 2 mm thin shell phantom with lossy ear that should
      give SARs within +/- 15% of those of anatomic models.

PMID- 12043817
TI  - Analysis of the picosecond magneto-optical phenomena in scattering media of
      biological interest.
AB  - The behaviour of a magneto-optically active biological-like medium under
      picosecond optical excitation is analysed. The new technique is based on the fact
      that photons trapped in multiple scattering events inside the magneto-optical
      medium leave the medium with larger induced rotation angles, as they travel
      longer distances. Two- and three-dimensional displacements of the photons in the
      medium are separately analysed. The dependence of this effect on the applied
      magnetic field strength, the value of the magneto-optical constant of the medium
      and the standard deviation of the statistical distribution of the photons
      scattered inside the turbid medium are studied. The best values for the magnetic
      field and optical parameters of the biological medium are proposed for the
      experimental observation of the picosecond magneto-optical phenomena in
      scattering media of biological origin. We also make some prospective studies to
      evaluate the potential application of the magneto-optical effect as a tool for
      optical tissue biopsy. Values for the optimum magnetic field intensities and for
      the expected experimental sensitivity in diverse conditions are reported.

PMID- 12043818
TI  - In vivo sonoluminescence imaging with the assistance of FCLA.
AB  - In this paper, sonoluminescence of tissues is reported for the first time. A
      sonoluminescence image of a living animal was obtained with a high-sensitivity
      imaging system. Furthermore, to enhance biological sonoluminescence,
      fluoresceinyl Cypridina luminescent analogue (FCLA), a chemiluminescence analysis
      agent, was used in the experiment. With the assistance of FCLA we succeeded in
      observing an image of a living animal with high contrast and good signal-to-noise
      ratio. This technique has potential applications in clinical diagnosis.

PMID- 12043819
TI  - Optimizing the assessment of age-related changes in trabecular bone.
AB  - The goal of this study was to develop an optimal procedure to determine age
      related changes in trabecular bone. The investigations were based on two
      dimensional images of the human vertebral trabecular bone specimens. The
      following indices of trabecular structure were considered: bone volume/total
      volume, star volume of the marrow cavity, Euler number and the probability of
      disconnection (straightforwardly connected with the number of separated parts of
      the network). To follow precisely the changes in the trabecular structure with
      age, a computer simulation model was used. Up to 35 years of physiological
      remodelling were simulated. The validation of the model calculations was based on
      a quantitative comparison with the data measured for older individuals. The
      simulations confirmed that the description of the age-related changes in the
      trabecular bone by means of the architectural parameter (star volume) constitutes
      a promising tool for subjects older than approximately 50 years. For individuals
      younger than approximately 50 years bone mineral density (bone volume/total
      volume) seems to be the best suited descriptor. The results suggest that the
      optimal diagnostic procedure is age-dependent and should not be limited to the
      bone mineral density measurement. The clinical usefulness of the procedure has
      been validated by examination of the CT images.

PMID- 12043820
TI  - A hybrid scatter correction for 3D PET based on an estimation of the distribution
      of unscattered coincidences: implementation on the ECAT EXACT HR+.
AB  - We implemented a hybrid scatter-correction method for 3D PET that combines two
      scatter-correction methods in a complementary way. The implemented scheme uses a
      method based on the discrimination of the energy of events (the estimation of
      trues method (ETM)) and an auxiliary method (the single scatter simulation method
      (SSSI) or the convolution-subtraction method (CONV)) in an attempt to increase
      the accuracy of the correction over a wider range of acquisitions. The ETM takes
      into account the scatter from outside the field-of-view (FOV), which is not
      estimated with the auxiliary method. On the other hand, the auxiliary method
      accounts for events that have scattered with small angles, which have an energy
      that cannot be discriminated from that of unscattered events using the ETM. The
      ETM uses the data acquired in an upper energy window above the photopeak (550-650
      keV) to obtain a noisy estimate of the unscattered events in the standard window
      (350-650 keV). Our implementation uses the auxiliary method to correct the
      residual scatter in the upper window. After appropriate scaling, the upper window
      data are subtracted from the total coincidences acquired in the standard window,
      resulting in the final scatter estimate, after smoothing. In this work we compare
      the hybrid method with the corrections used by default in the 2D and 3D modes of
      the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better
      with the hybrid method, although the relative errors of quantification were
      similar. We conclude that hybrid techniques such as the one implemented in this
      work can provide an accurate, general-purpose and practical way to correct the
      scatter in 3D PET, taking into account the scatter from outside the FOV.

PMID- 12043821
TI  - Influence of hypoxia on wavelength dependence of differential pathlength and near
      infrared quantification.
AB  - Continuous wave near-infrared spectroscopy (NIRS) measurements of cardiac
      correlated changes in attenuation in the adult human head were computed using a
      Fourier analysis technique that eliminates the positive error bias associated
      with the magnitude of the Fourier coefficient. These attenuation changes were
      used to determine wavelength dependence of differential pathlength, DP(lambda),
      at four stages during progressive hypoxia (21, 17, 13 and 9% FIO2) in normal
      volunteers. The effects of incorporating DP(lambda) into NIRS algorithms to
      compute relative concentration changes and absolute concentration of
      oxyhaemoglobin and deoxyhaemoglobin are discussed. Because variations in
      DP(lambda) are restricted to wavelengths below 780 nm, absolute concentration
      calculations are influenced by hypoxia-induced changes while relative
      concentrations are unaffected. However, even accounting for changes in DP(lambda)
      did not allow computation of physiologically reasonable absolute concentrations
      of the haemoglobin species.

PMID- 12043822
TI  - Arterial embolization hyperthermia: hepatic iron particle distribution and its
      potential determination by magnetic resonance imaging.
AB  - Arterial embolization hyperthermia (AEH) consists of arterially embolizing liver
      tumours with ferromagnetic particles that generate hysteretic heating on exposure
      to an alternating magnetic field. A critical component of AEH is the
      concentration and distribution of ferromagnetic particles in the normal hepatic
      parenchyma (NHP), as well as in the tumour tissue. If the distribution of
      particles in NHP is heterogeneous, with areas of high concentration, then
      unwanted areas of necrosis may result during AEH. Using an in vivo rabbit liver
      tumour model, this study showed that hepatic arterial infusion of ferromagnetic
      particles does indeed result in a heterogeneous distribution of iron in NHP. The
      radiological technique of magnetic resonance imaging (MRI) was then evaluated as
      a potential tool for non-invasively and prospectively determining the
      concentration and distribution of particles within the hepatic tumour and NHP
      following hepatic arterial infusion. A preliminary in vitro experiment showed
      that although the concentration of iron within the tumour tissue (1.92-3.50 mg of
      iron per gram of tissue) was too great to measure, MRI was able to accurately
      determine the lower iron concentration (0.10-0.53 mg of iron per gram of tissue)
      in NHP. Further work is needed to evaluate MRI under in vivo conditions. If
      successful, MRI could become an important component of an emerging novel
      treatment for advanced hepatic malignancies.

PMID- 12043823
TI  - Theoretical evaluation of moderately focused spherical transducers and multi
      focus acoustic lens/transducer systems for ultrasound thermal therapy.
AB  - Impractically long treatment times are required for highly focused spherical
      transducers to destroy large tumours because thermal lesions generated by these
      transducers are small and a large number of such lesions are required. Moderately
      focused spherical transducers and multi-focus acoustic lens/transducer systems
      can generate larger thermal lesions compared to those produced by highly focused
      spherical transducers, and therefore shorter treatment times can be expected. The
      decrease in total treatment time by the use of moderately focused spherical
      transducers and acoustic lens/transducer systems was quantified in this study. A
      3D ultrasound thermal model was developed to predict thermal lesion volumes
      generated by ultrasound transducers. A target model was constructed in order to
      compare various transducer designs under identical treatment conditions and with
      identical treatment goals. A design method was developed to determine the
      thickness of lens elements for production of specified multi-focus fields. Then,
      a highly focused and a moderately focused spherical transducer, and an acoustic
      lens/transducer system were compared in terms of total time required to treat a
      tumour. These transducers had identical apertures and operating frequencies. The
      radius of curvature of the moderately focused spherical transducer was chosen
      such that the length of thermal lesions it generated over 10 s single exposures
      was slightly greater than that of the target. The lens/transducer system was
      designed to produce a 9 focus field. The simulation results show that for the
      treatment of a 2 x 2 x 2 cm3 tumour at a depth of 5 cm in the body, the highly
      focused spherical transducer, the moderately focused spherical transducer and the
      lens/transducer system required 150, 42 and 30 min, respectively.

PMID- 12043824
TI  - Room scatter studies in the air kerma strength standardization of the Amersham
      CDCS-J-type 137Cs source: a Monte Carlo study.
AB  - Corrections for room scatter, [kSC (d, H)]RM, as a function of source-to-detector
      distance, d, and source-to-floor-height, H, and also departure from constant room
      scatter. ks1, have been computed for rooms of various sizes using Monte Carlo
      methods for air kerma strength standardization of the Amersham CDCS-J-type 137Cs
      brachytherapy source. These corrections will also be applicable to any type of
      137Cs source that may be considered for standardization. It was found that,
      depending upon the relative position of the source with respect to the
      surrounding concrete scattering surfaces (side walls, floor and ceiling) and
      different set of d values, the assumption of constant room scatter overestimated
      the air kerma strength, Sk, by between 0.2% and 0.6%.

PMID- 12043825
TI  - The use of plane-parallel chambers in electron dosimetry without any cross
      calibration.
AB  - Current dosimetry protocols from AAPM, DIN and IAEA recommend a cross-calibration
      for plane-parallel chambers against a calibrated thimble chamber for electron
      dosimetry. The rationale for this is the assumed chamber-to-chamber variation of
      plane-parallel chambers and the large uncertainty in the wall perturbation factor
      (p(wall)60Co)pp at 60Co for plane-parallel chambers. We have confirmed the
      results of other authors that chamber-to-chamber variation of the investigated
      chambers of types Roos, Markus, Advanced Markus and Farmer is less than 0.3%.
      Starting with a calibration factor for absorbed dose to water and on the basis of
      the three dosimetry protocols AAPM TG-51, DIN 6800-2 (slightly modified) and IAEA
      TRS-398, values for (p(wall)60Co)Roos of 1.024 +/- 0.005, (p(wall)60Co)Markus of
      1.016 +/- 0.005 and (p(wall)60Co)Advanced Markus of 1.014 +/- 0.005 have been
      determined. In future this will permit electron dosimetry with the above-listed
      plane-parallel chambers having a calibration factor N(D, w)60Co without the
      necessity for cross-calibration against a thimble chamber.

PMID- 12043826
TI  - A mathematical analysis of the 4 x 100 m relay.
AB  - In this study, we examined aspects of the 4 x 100 m relay that are amenable to
      mathematical analysis. We looked at factors that affect the time required to
      complete the relay, focusing on the performance of elite male athletes. Factors
      over which the individual athletes, and the team coach, can exercise some control
      are: the starting positions of the runners on legs 2, 3 and 4, the positions at
      which baton exchanges occur, the free distances at the baton exchanges and the
      running order of the athletes. The lane draw is shown to have an important
      influence on the relay time, although it is outside the control of the team
      coach. Teams drawn in the outside lanes benefit from the inverse relation between
      bend radius of curvature and running speed. For teams composed of athletes with
      different times over 100 m, we show that the fastest relay times are achieved
      with the fastest athlete taking the first leg, with the slowest two runners
      allocated to the final two legs.

PMID- 12043827
TI  - Kinematic analysis of butterfly turns of international and national swimmers.
AB  - The aims of this study were (1) to evaluate the different turn phases of 200 m
      butterfly during competition in a 50 m pool, (2) to determine if wall contact
      times are related to swim speed and (3) to compare the turn variables of a
      European Champion with other swimmers. In the first part of the study, we
      assessed the turns of 22 swimmers ranked in three groups according to 200 m
      butterfly swim performance (fast group = 121.73+/-3.03 s, intermediate group =
      126.25+/-0.55 s, slow group = 129.24+/-2.30 s). Two turn times were recorded: the
      first before the turn (i.e. the time it takes the swimmer's head to reach the
      wall from 7.5 m away) and the second after the turn (i.e. the time from the wall
      to the point at which the swimmer's head passes 7.5 m away). The third turn was
      performed significantly faster by the fast group than by the slow group, both
      before (P< 0.01) and after (P< 0.02) the turn. In the second part of the study,
      objectives (2) and (3) were evaluated among 15 swimmers based on a specific
      protocol. Three cameras (50 Hz) simultaneously recorded the turn; these were
      placed above the water 10 m before the wall, 5 m before and just above the wall.
      Longer contact times of the feet on the wall were associated with a faster push
      off speed (P < 0. 02). The European Champion achieved an improved contact time
      while performing a rapid pull-out speed.

PMID- 12043828
TI  - Measurement of total energy expenditure by the doubly labelled water method in
      professional soccer players.
AB  - To determine the daily energy requirements of professional soccer players during
      a competitive season, we measured total energy expenditure in seven players (age
      22.1+/-1.9 years, height 1.75+/-0.05 m, mass 69.8+/-4.7 kg; mean +/- s) using the
      doubly labelled water method. Energy intake was simultaneously estimated from 7
      day self-report dietary records. Mean total energy expenditure and energy intake
      were 14.8+/-1.7 MJ x day(-1) (3532+/-408 kcal x day(-1)) and 13.0+/-2.4 MJ x day(
      1) (3113+/-581 kcal x day(-1)), respectively. Although there was a significant
      difference between total energy expenditure and energy intake (P < 0.01), there
      was a strong relationship between the two (r= 0.893, P< 0.01). Basal metabolic
      rate and recommended energy allowance calculated from the Recommended Dietary
      Allowances for the Japanese were 7.0+/-0.3 MJ x day(-1) (1683+/-81 kcal x day(
      1)) and 15.6+/-0.8 MJ x day(-1) (3739+/-180 kcal x day(-1)), respectively. A
      physical activity level (total energy expenditure/ basal metabolic rate) of
      2.11+/-0.30 indicated that, during the competitive season, professional soccer
      players undertake much routine physical activity, similar to that of competitive
      athletes during moderate training. Energy intake estimated using dietary records
      was under-reported, suggesting that its calculation from these data does not
      predict energy expenditure in soccer players.

PMID- 12043829
TI  - Influence of physiological characteristics on selection in a semi-professional
      first grade rugby league team: a case study.
AB  - The aim of this study was to determine whether the physiological characteristics
      of players influence selection in a semi-professional first grade rugby league
      team. Sixty-six semi-professional rugby league players aged 24+/-4 years (mean +/
      s) were monitored over two competitive seasons. The players underwent
      measurements of body mass, muscular power (vertical jump), speed (10, 20, 30 and
      40 m sprint), agility (Illinois agility run) and estimated maximal aerobic power
      (multi-stage fitness test) 1 week before their first competition match. After
      selection for either the first or second grade team, the results of all
      physiological tests were collated and analysed to determine if there were any
      physiological differences between players selected for the two teams. Players
      selected to play in the first grade team were significantly (P< 0.05) older (25+/
      4 vs 22+/-4 years) and heavier (93+/-10 vs 86+/-10 kg) and had more playing
      experience (18+/-6 vs 15+/-6 years) than second grade players. Muscular power,
      speed, agility and estimated maximal aerobic power were not significantly
      different (P > 0.05) between first grade and second grade players. These results
      suggest that the physiological capacities of players do not influence selection
      in a semi-professional first grade rugby league team. Rather, player selection
      appears to be based on body mass, playing experience and skill. These results
      support the need for a standardized skills performance test for semi-professional
      rugby league players.

PMID- 12043830
TI  - The influence of ventilatory control on heart rate variability in children.
AB  - The aim of this study was to determine the influence of breathing frequency and
      tidal volume on resting heart rate variability in children aged 9 years (n = 29)
      and 16 years (n = 19). Heart rate variability was measured in four conditions:
      (1) without the control of ventilation followed at random by (2) a fixed
      breathing frequency of 12 breaths x min(-1), (3) a breathing frequency of 12
      breaths x min(-1) but with a fixed tidal volume of 30% vital capacity and (4) a
      fixed breathing frequency of 6 breaths x min(-1) and a tidal volume of 30% vital
      capacity. A total of 128 RR intervals (the time between two spikes in the heart
      rate) were detected and absolute high- and low-frequency spectral components were
      calculated using autoregressive modelling. The younger children were unable to
      control ventilation to achieve conditions 3 and 4; therefore, a 2 x 2 (group x
      condition) analysis of variance was used to analyse conditions 1 and 2. There
      were significant interactions between group and heart rate variability conditions
      for the low-frequency component and the ratio of low to high frequencies (P <
      0.001). The main effect for condition showed that at 12 breaths x min(-1) with no
      fixed tidal volume there was a significantly higher standard deviation of the RR
      interval, total power and high-frequency (P< 0.01) and low-frequency spectral
      components (P < 0.05) than in the condition with no ventilatory control. Across
      the four breathing conditions for the older participants, the high-frequency
      spectral component was significantly higher in the condition at 6 breaths x min(
      1) with a fixed tidal volume than in that with no ventilatory control (P <
      0.005); the ratio of high to low frequencies was significantly lower for the
      spontaneous condition than those performed at 12 breaths x min(-1) (P < 0.001).
      The results provide evidence of the need for ventilatory control when assessing
      short-term resting heart rate variability in children.

PMID- 12043831
TI  - The effect of exercise-induced muscle damage on isometric and dynamic knee
      extensor strength and vertical jump performance.
AB  - In this study, we assessed the effect of exercise-induced muscle damage on knee
      extensor muscle strength during isometric, concentric and eccentric actions at
      1.57 rad x s(-1) and vertical jump performance under conditions of squat jump,
      countermovement jump and drop jump. The eight participants (5 males, 3 females)
      were aged 29.5+/-7.1 years (mean +/- s). These variables, together with plasma
      creatine kinase (CK), were measured before, 1 h after and 1, 2, 3, 4 and 7 days
      after a bout of muscle damaging exercise: 100 barbell squats (10 sets x 10
      repetitions at 70% body mass load). Strength was reduced for 4 days (P< 0.05) but
      no significant differences (P> 0.05) were apparent in the magnitude or rate of
      recovery of strength between isometric, concentric and eccentric muscle actions.
      The overall decline in vertical jump performance was dependent on jump method:
      squat jump performance was affected to a greater extent than countermovement
      (91.6+/-1.1% vs 95.2+/-1.3% of pre-exercise values, P< 0.05) and drop jump
      (95.2+/-1.4%, P< 0.05) performance. Creatine kinase was elevated (P < 0.05) above
      baseline 1 h after exercise, peaked on day 1 and remained significantly elevated
      on days 2 and 3. Strength loss after exercise-induced muscle damage was
      independent of the muscle action being performed. However, the impairment of
      muscle function was attenuated when the stretch-shortening cycle was used in
      vertical jumping performance.

PMID- 12043832
TI  - Effect of creatine supplementation on phosphocreatine resynthesis, inorganic
      phosphate accumulation and pH during intermittent maximal exercise.
AB  - In this study, we examined the effect of creatine ingestion on muscle power
      output, muscle phosphocreatine resynthesis, inorganic phosphate and pH during
      repeated brief bouts of maximal exercise. Nine healthy males performed maximal
      plantar flexion before and after creatine ingestion (20 g x day(-1) for 6 days).
      The experimental protocol consisted of five 8 s bouts (bouts 1-5) interspersed
      with 30 s recovery, followed by bouts 6 (8 s) and 7 (16 s) separated by 1 and 2
      min, respectively. Muscle phosphocreatine, inorganic phosphate and pH were
      estimated every 16 s by 31P magnetic resonance spectroscopy. After creatine
      ingestion, muscle power output increased by approximately 5% (P< 0.05) from bouts
      3 to 7 and muscle phosphocreatine resynthesis increased (P< 0.05) during 10 min
      recovery. The higher phosphocreatine concentration observed after only 30 s of
      recovery was accompanied by lower inorganic phosphate accumulation and higher pH.
      Strong correlations were found between exercise power restoration and the
      corresponding pre-exercise phosphocreatine and inorganic phosphate concentrations
      and muscle pH after creatine ingestion. The better maintenance of muscle power
      output observed after creatine ingestion was attributed to a higher rate of
      phosphocreatine resynthesis, lower accumulation of inorganic phosphate and higher
      pH.

PMID- 12043833
TI  - Molecular basis of neuroprotective activities of rasagiline and the anti
      Alzheimer drug TV3326 [(N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate].
AB  - Rasagiline (N-propargyl-1-(R)-aminoindan) is a selective, irreversible monoamine
      oxidase B (MAO B) inhibitor which has been developed as an anti-Parkinson drug.
      In controlled monotherapy and as adjunct to L-dopa it has shown anti-Parkinson
      activity. In cell culture (PC-12 and neuroblastoma SH-SY5Y cells) it exhibits
      neuroprotective and anti-apoptotic activity against several neurotoxins (SIN-1,
      MPTP, 6-hydroxydopamine and N-methyl-(R)-salsolinol) and ischemia. In vivo, it
      reduces the sequelae of traumatic brain injury in mice and speeds their recovery.
      The neuroprotective activity of rasagaline does not result from MAO B inhibition,
      since its S-enantiomer, TVP1022, which has 1000-fold weaker MAO inhibitory
      activity, exhibits similar neuroprotective properties. Introduction of a
      carbamate moiety into the rasagiline molecule to confer cholinesterase inhibitory
      activity for the treatment of Alzheimer's disease, resulted in compounds TV3326
      [(N-Propargyl-(3R)Aminoindan-5-YL)-Ethyl Methyl Carbamate] and its S-enantiomer
      TV3279 [(N-Propargyl-(3S)Aminoindan-5-YL)-Ethyl Methyl Carbamate], which retain
      the neuroprotective activities of rasagiline and TVP1022. They also antagonize
      scopolamine-induced impairments in spatial memory. In addition, TV3326 exhibits
      brain-selective MAO A and B inhibitory activity after chronic administration and
      has antidepressant-like activity in the forced swim test. This is associated with
      an increase in brain levels of serotonin. The anti-apoptotic activity of these
      propargylamine-containing derivatives may be related to their ability to delay
      the opening of voltage-dependent anion channels (VDAC), which are part of the
      mitochondrial permeability transition pore. The propargylamine moiety is
      responsible for the increase in the mitochondrial family of Bcl-2 proteins,
      prevention in the fall in mitochondrial membrane potential, prevention of the
      activation of caspase 3, and of translocation of glyceraldehyde-3-phosphate
      dehydrogenase from the cytoplasm to the nucleus. The latter processes are closely
      associated with neurotoxin-induced apoptosis. Rasagiline interacts with and
      prevents the binding of PKI 1195 to the pro-apoptotic peripheral benzodiazepine
      receptor, which together with Bcl-2, hexokinase, porin, and adenine nucleotide
      translocator constitutes part of the VDAC. Furthermore, rasagiline, TV3326 and
      TV3279 are able to influence the processing of amyloid precursor protein by
      activation of alpha-secretase and increasing the release of soluble alpha APP in
      rat PC-12 and human neuroblastoma SH-SY5Y cells and in rat and mice cortex and
      hippocampus. This process has been shown to involve the upregulation of PKC and
      MAP kinase. It is quite likely that the induction of Bcl-2 and activation of PKC
      by rasagiline and TV3326 is closely linked to the anti-apoptotic action of these
      drugs and their ability to process APP by activation of alpha-secretase.

PMID- 12043835
TI  - Calcium, protease activation, and cytoskeleton remodeling underlie growth cone
      formation and neuronal regeneration.
AB  - The cytoarchitecture, synaptic connectivity, and physiological properties of
      neurons are determined during their development by the interactions between the
      intrinsic properties of the neurons and signals provided by the microenvironment
      through which they grow. Many of these interactions are mediated and translated
      to specific growth patterns and connectivity by specialized compartments at the
      tips of the extending neurites: the growth cones (GCs). The mechanisms underlying
      GC formation at a specific time and location during development, regeneration,
      and some forms of learning processes, are therefore the subject of intense
      investigation. Using cultured Aplysia neurons we studied the cellular mechanisms
      that lead to the transformation of a differentiated axonal segment into a motile
      GC. We found that localized and transient elevation of the free intracellular
      calcium concentration ([Ca2+]i) to 200-300 microM induces GC formation in the
      form of a large lamellipodium that branches up into growing neurites. By using
      simultaneous on-line imaging of [Ca2+]i and of intraaxonal proteolytic activity,
      we found that the elevated [Ca2+]i activate proteases in the region in which a GC
      is formed. Inhibition of the calcium-activated proteases prior to the local
      elevation of the [Ca2+]i blocks the formation of GCs. Using retrospective
      immunofluorescent methods we imaged the proteolysis of the submembrane spectrin
      network, and the restructuring of the cytoskeleton at the site of GC formation.
      The restructuring of the actin and microtubule network leads to local
      accumulation of transported vesicles, which then fuse with the plasma membrane in
      support of the GC expansion.

PMID- 12043834
TI  - Molecular aspects of retinal degenerative diseases.
AB  - Retinal degeneration, either acquired or inherited, is a major cause of visual
      impairment and blindness in humans. Inherited retinal degeneration comprises a
      large group of diseases that result in the loss of photoreceptor cells. To date,
      131 retinal disease loci have been identified, and 76 of the genes at these loci
      have been isolated (RetNet Web site). Several of these genes were first
      considered candidates because of their chromosomal localization or homology to
      genes involved in retinal degeneration in other organisms. In this review, I will
      discuss recent advances in the identification of genes that cause retinal
      degeneration, and I will describe the mechanisms of photoreceptor death and
      potential treatments for retinal degenerative diseases.

PMID- 12043836
TI  - Melatonin-dopamine interactions: from basic neurochemistry to a clinical setting.
AB  - To review the interaction between melatonin and the dopaminergic system in the
      hypothalamus and striatum and its potential clinical use in dopamine-related
      disorders in the central nervous system. Medline-based search on melatonin
      dopamine interactions in mammals. Melatonin. the hormone produced by the pineal
      gland at night. influences circadian and seasonal rhythms, most notably the sleep
      wake cycle and seasonal reproduction. The neurochemical basis of these activities
      is not understood yet. Inhibition of dopamine release by melatonin has been
      demonstrated in specific areas of the mammalian central nervous system
      (hypothalamus, hippocampus, medulla-pons, and retina). Antidopaminergic
      activities of melatonin have been demonstrated in the striatum. Dopaminergic
      transmission has a pivotal role in circadian entrainment of the fetus, in
      coordination of body movement and reproduction. Recent findings indicate that
      melatonin may modulate dopaminergic pathways involved in movement disorders in
      humans. In Parkinson patients melatonin may, on the one hand, exacerbate symptoms
      (because of its putative interference with dopamine release) and, on the other,
      protect against neurodegeneration (by virtue of its antioxidant properties and
      its effects on mitochondrial activity). Melatonin appears to be effective in the
      treatment of tardive dyskinesia. a severe movement disorder associated with long
      term blockade of the postsynaptic dopamine D2 receptor by antipsychotic drugs in
      schizophrenic patients. The interaction of melatonin with the dopaminergic system
      may play a significant role in the nonphotic and photic entrainment of the
      biological clock as well as in the fine-tuning of motor coordination in the
      striatum. These interactions and the antioxidant nature of melatonin may be
      beneficial in the treatment of dopamine-related disorders.

PMID- 12043837
TI  - Harnessing the immune system for neuroprotection: therapeutic vaccines for acute
      and chronic neurodegenerative disorders.
AB  - Nerve injury causes degeneration of directly injured neurons and the damage
      spreads to neighboring neurons. Research on containing the damage has been mainly
      pharmacological, and has not recruited the immune system. We recently discovered
      that after traumatic injury to the central nervous system (spinal cord or optic
      nerve), the immune system apparently recognizes certain injury-associated self
      compounds as potentially destructive and comes to the rescue with a protective
      antiself response mediated by a T-cell subpopulation that can recognize self
      antigens. We further showed that individuals differ in their ability to manifest
      this protective autoimmunity, which is correlated with their ability to resist
      the development of autoimmune diseases. This finding led us to suggest that the
      antiself response must be tightly regulated to be expressed in a beneficial
      rather than a destructive way. In seeking to develop a neuroprotective therapy by
      boosting the beneficial autoimmune response to injury-associated self-antigens,
      we looked for an antigen that would not induce an autoimmune disease. Candidate
      vaccines were the safe synthetic copolymer Cop-1, known to cross-react with self
      antigens, or altered myelin-derived peptides. Using these compounds as vaccines,
      we could safely boost the protective autoimmune response in animal models of
      acute and chronic insults of mechanical or biochemical origin. Since this
      vaccination is effective even when given after the insult, and because it
      protects against the toxicity of glutamate (the most common mediator of secondary
      degeneration), it can be used to treat chronic neurodegenerative disorders such
      as glaucoma, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral
      sclerosis.

PMID- 12043838
TI  - The TRP channel and phospholipase C-mediated signaling.
AB  - Drosophila photoreceptors use a phospholipase C-mediated signaling for
      phototransduction. This pathway begins by light activation of a G-protein-coupled
      photopigment and ends by activation of the TRP and TRPL channels. The Drosophila
      TRP protein is essential for the high Ca2+ permeability and constitutes the major
      component of the light-induced current, thereby affecting both excitation and
      adaptation of the photoreceptor cell. TRP is the prototype of a large and diverse
      multigene family whose members are sharing a structure, which is conserved
      through evolution from the worm Caenorhabditis elegans to humans. TRP-related
      channel proteins are found in a variety of cells and tissues and show a large
      functional diversity although the gating mechanism of Drosophila TRP and of other
      TRP-related channels is still unknown.

PMID- 12043839
TI  - Gene therapy for glioblastoma: future perspective for delivery systems and
      molecular targets.

PMID- 12043841
TI  - Frequent blood-brain barrier disruption in the human cerebral cortex.
AB  - 1. The blood-brain barrier (BBB) protects the brain from circulating xenobiotic
      agents. The pathophysiology, time span, spatial pattern, and pathophysiological
      consequences of BBB disruptions are not known. 2. Here, we report the
      quantification of BBB disruption by measuring enhancement levels in computerized
      tomography brain images. 3. Pathological diffuse enhancement associated with
      elevated albumin levels in the cerebrospinal fluid (CSF) was observed in the
      cerebral cortex of 28 out of 43 patients, but not in controls. Four patients
      displayed weeks-long focal BBB impairment. In 19 other patients, BBB disruption
      was significantly associated with elevated blood pressure, body temperature,
      serum cortisol, and stress-associated CSF 'readthrough" acetylcholinesterase.
      Multielectrode electroencephalography revealed enhanced slow-wave activities in
      areas of focal BBB disruption. Thus, quantification of BBB disruption using
      minimally invasive procedures, demonstrated correlations with molecular,
      clinical, and physiological stress-associated indices. 4. These sequelae
      accompany a wide range of neurological disorders, suggesting that persistent,
      detrimental BBB disruption is considerably more frequent than previously assumed.

PMID- 12043840
TI  - Involvement of nuclear factor-kappaB in endothelin-A-receptor-induced
      proliferation and inhibition of apoptosis.
AB  - Endothelins have been implicated in the regulation of cell proliferation,
      differentiation, and apoptosis, but the mechanisms of these complex events are
      not yet fully understood. Although the nuclear factor-kappaB (NF-kappaB) was
      shown to play a prominent role in the above processes, its participation in
      endothelin receptor A (ET(A)R) signaling has not been previously demonstrated.
      This study provides evidence that NF-kappaB is involved in ET(A)R-induced
      proliferation and inhibition of apoptosis. Endothelin (ET)-1, ET-3, and
      sarafotoxin b induce cell proliferation and prevent apoptosis induced by serum
      deprivation in a Chinese hamster lung (CCL39) cell line that stably expresses
      ET(A)R (CCL39ET(A)). Activation of ET(A)R resulted in enhanced DNA-binding
      activity of NF-kappaB and degradation of IkappaB-alpha. Expression of the
      dominant negative form of IkappaB-alpha (IkappaB deltaN) inhibited the
      proliferative activities mediated by ET(A)R as well as its anti-apoptotic
      activities. Treatment of the cells with prostaglandin A1, an inhibitor of IkappaB
      kinase-beta, reduced ET-1-induced proliferation and its anti-apoptotic effect.
      These findings indicate that the regulation of cell proliferation and apoptosis
      by ET(A)R is mediated by the ET(A)R-activated NF-kappaB.

PMID- 12043842
TI  - Antiaggregating antibody raised against human PrP 106-126 recognizes pathological
      and normal isoforms of the whole prion protein.
AB  - Antibodies to the prion protein (PrP) have been critical to the neuropathological
      and biochemical characterization of PrP-related degenerative diseases in humans
      and animals. Although PrP is highly conserved evolutionarily, there is some
      sequence divergence among species; as a consequence, anti-PrP antibodies have a
      wide spectrum of reactivity when challenged with PrP from diverse species. We
      have produced an antibody [monoclonal antibody (mAb) 2-40] raised against a
      synthetic peptide corresponding to residues (106-126 of human PrP and have
      characterized it by epitope mapping, Western immunoblot analysis, and
      immunohistochemistry. The antibody recognizes not only human PrP isoforms but
      also pathological PrP from all species tested (i.e., sheep, hamsters, and mice).
      Together with the fact that it recognizes the whole PrP in both cellular and
      scrapie isoforms, mAb 2-40 may be helpful in studying conformational changes of
      the PrP, as well as establishing a possible connection between human and animal
      diseases.

PMID- 12043843
TI  - Evaluation of the neurotoxic activity of typical and atypical neuroleptics:
      relevance to iatrogenic extrapyramidal symptoms.
AB  - Typical neuroleptic therapy often results in extrapyramidal symptoms (EPS) and
      tardive dyskinesia (TD). Recent reports reveal neurotoxic activity in some
      neuroleptics. We hypothesized that neurotoxicity might be implicated in EPS. This
      study aims to evaluate the neurotoxic activity of typical and atypical
      neuroleptics and to determine the possible role of neurotoxicity in neuroleptic
      induced EPS. Perphenazine, haloperidol, clozapine, sulpiride, and risperidone (10
      100 microM) were administered, either alone or combined with dopamine, to primary
      mouse neuronal or intact brain culture and to a human neuroblastoma (NB) cell
      line (SK-N-SH). Cell viability (measured by neutral red and alamar blue), DNA
      fragmentation (flow cytometry-NB) were determined. Neuroblastoma: perphenazine,
      clozapine, and haloperidol (100 microM) decreased viability by 87, 43, and 34%
      respectively. Sulpiride and risperidone were not toxic. At 10 microM, toxicity
      decreased markedly. Dopamine (125 microM) potentiated the perphenazine-induced
      toxicity. Flow cytometry of NB cells treated with perphenazine (2.5-40 microM)
      showed an increase (perphenazine 20 microM, 40 microM, 48 h) in fragmented DNA
      (74.7% and 95.0% vs. 8.7% in controls). Lower concentrations increased the G1
      phase and decreased S phase in the cell cycle. In primary neurons, perphenazine,
      haloperidol, and clozapine, but not risperidone and sulpiride, induced a
      significant neurotoxic effect, which, in intact brain culture, was absent
      (haloperidol and clozapine) or lowered (perphenazine). Dopamine (0.5 mM) did not
      modify the effect of the drugs in the primary cultures. Neuroleptics possess
      differential neurotoxic activity with higher sensitivity of neoplasm tissue (NB
      compared to primary cultures). The order of toxicity was perphenazine >
      haloperidol = clozapine:sulpiride and risperidone were not toxic. Neurotoxicity
      is independent of dopamine and is associated with cell cycle arrest and
      apoptosis. With the exception of clozapine, neurotoxicity seems relevant to
      neuroleptic-induced EPS and TD.

PMID- 12043844
TI  - The voltage-gated Ca2+ channel is the Ca2+ sensor of fast neurotransmitter
      release.
AB  - Previously it demonstrated that in the absence of Ca2+ entry, evoked secretion
      occurs neither by membrane depolarization, induction of [Ca2+]i rise, nor by both
      combined (Ashery, U., Weiss, C., Sela, D., Spira, M. E., and Atlas, D. (1993).
      Receptors Channels 1:217-220.). These studies designate Ca2+ entry as opposed to
      [Ca2+]i rise, essential for exocytosis. It led us to propose that the channel
      acts as the Ca+ sensor and modulates secretion through a physical and functional
      contact with the synaptic proteins. This view was supported by protein-protein
      interactions reconstituted in the Xenopus oocytes expression system and release
      experiments in pancreatic cells (Barg, S., Ma, X., Elliasson, L., Galvanovskis,
      J., Gopel, S. O., Obermuller, S., Platzer, J., Renstrom, E., Trus, M., Atlas, D.,
      Streissnig, G., and Rorsman, P. (2001). Biophys. J; Wiser, O., Bennett, M. K.,
      and Atlas, D. (1996). EMBO J 15:4100-4110; Wiser, O., Trus, M.. Hernandez, A.,
      Renstrom, E., Barg, S., Rorsman. P., and Atlas, D. (1999). Proc. Natl. Acad. Sci.
      U.S.A. 96:248-253). The kinetics of Ca(v)1.2 (Lc-type) and Ca(v)2.2 (N-type) Ca2+
      channels were modified in oocytes injected with cRNA encoding syntaxin 1A and
      SNAP-25. Conserved cysteines (Cys271, Cys272) within the syntaxin 1A
      transmembrane domain are essential. Synaptotagmin 1, a vesicle-associated
      protein, accelerated the activation kinetics indicating Ca(v)2.2 coupling to the
      vesicle. The unique modifications of Ca(v)1.2 and Ca(v)2.2 kinetics by syntaxin
      1A, SNAP-25, and synaptotagmin combined implied excitosome formation, a primed
      fusion complex of the channel with synaptic proteins. The Ca(v)1.2 cytosolic
      domain Lc(753-893), acted as a dominant negative modulator, competitively
      inhibiting insulin release of channel-associated vesicles (CAV), the readily
      releasable pool of vesicles (RRP) in islet cells. A molecular mechanism is
      offered to explain fast secretion of vesicles tethered to SNAREs-associated Ca2+
      channel. The tight arrangement facilitates the propagation of conformational
      changes induced during depolarization and Ca2+-binding at the channel, to the
      SNAREs to trigger secretion. The results imply a rapid Ca2+-dependent CAV (RRP)
      release, initiated by the binding of Ca2+ to the channel, upstream to
      intracellular Ca2+ sensor thus establishing the Ca2+ channel as the Ca2+ sensor
      of neurotransmitter release.

PMID- 12043845
TI  - Emotion-perception interplay in the visual cortex: "the eyes follow the heart".
AB  - Emotive aspects of stimuli have been shown to modulate perceptual thresholds.
      Lately, studies using functional Magnetic Resonance Imaging (fMRI) showed that
      emotive aspects of visual stimuli activated not only canonical limbic regions,
      but also sensory areas in the cerebral cortex. However, it is still arguable to
      what extent such emotive, related activation in sensory areas of the cortex are
      affected by physical characteristic or attribute difference of stimuli. To
      manipulate valence of stimuli while keeping visual features largely unchanged, we
      took advantage of the Expressional Transfiguration (ET) of faces. In addition, to
      explore the sensitivity of high level visual regions, we compared repeated with
      unrepeated (i.e. different) stimuli presentations (fMR adaptation). Thus, the
      dynamics of brain responses was determined according to the relative signal
      reduction during "repeated" relative to "different" presentations ("adaptation
      ratio"). Our results showed, for the first time, that emotional valence produced
      significant differences in fMR adaptation, but not in overall levels of
      activation of lateral occipital complex (LOC). We then asked whether this emotion
      modulation on sensory cortex could be related to previous personal experience
      that attached negative attributes of stimuli. To clarify this, we investigated
      Posttraumatic Stress Disorder (PTSD) and non-PTSD veterans. PTSD is characterized
      by recurrent revival of trauma-related sensations. Such phenomena have been
      attributed to a disturbed processing of trauma-related stimuli, either at the
      perceptual level or at the cognitive level. We assumed that PTSD veterans would
      differ from non-PTSD veterans (who have similar combat experience) in their high
      order visual cortex responses to combat-related visual stimuli that are
      associated with their traumatic experience. An fMRI study measured the cerebral
      activation of subjects while viewing pictures with and without combat content, in
      "repeated" or "different" presentation conditions. The emotive effect on the
      visual cortex was found, again, only in the fMR-adaptation paradigm. Visual
      cortical regions showed significant differences between PTSD and non-PTSD
      veterans only in "repeated" presentations of trauma-related stimuli (i.e.
      combat). In these regions, PTSD veterans showed less decrease in signal with
      repeated presentations of the same combat-related stimuli. This finding points to
      the possibility that traumatic experience modulates brain activity at the level
      of sensory cortex itself.

PMID- 12043846
TI  - Neuregulin induces sustained reactive oxygen species generation to mediate
      neuronal differentiation.
AB  - Neuregulins (NRGs), which are highly expressed in the nervous system, bind and
      activate two receptor tyrosine kinases, ErbB-3 and ErbB-4. Recently, we have
      shown that ErbB-4 receptors expressed in PC12 cells mediate NRG-induced
      differentiation through the MAPK signaling pathway. Here we demonstrate that NRG
      induces an increase in the intracellular concentration of reactive oxygen species
      (ROS). N-acetylcysteine, a ROS scavenger, inhibited NRG-induced activation of Ras
      and Erk and PC12-ErbB-4 cell differentiation. These results suggest that ROS
      production is involved in NRG-mediated neuronal differentiation and that ROS can
      regulate activation of Ras and Erk. Constitutively active Ras enhanced ROS
      production and dominant negative Ras inhibited NRG-induced ROS production,
      suggesting, a positive regulatory loop between Ras and ROS. The mitogen, EGF,
      induced short-term ROS production whereas NRG and NGF, which induce cell
      differentiation, induced prolonged ROS production. These results strongly suggest
      that the kinetics of ROS production may determine whether the cells will
      differentiate or proliferate.

PMID- 12043847
TI  - 6-Hydroxydopamine increases ubiquitin-conjugates and protein degradation:
      implications for the pathogenesis of Parkinson's disease.
AB  - One of the hallmarks of Parkinson's disease (PD) is pathological structure,
      termed Lewy body, containing inclusions of ubiquitinated proteins in the
      dopaminergic neurons in the substantia nigra. The mechanism leading to the
      formation of these aggregates is unclear, although it has been shown that
      mutations in alpha-synuclein or in the ubiquitin-related enzyme UCH-L1 might
      induce such protein aggregation. We, therefore, examined the possible role of 6
      hydroxydopamine (6-OHDA), a dopaminergic neurotoxin used in PD experimental
      models, in causing protein degradation and its association with the ubiquitin
      system. Using antiubiquitin antibodies we found that exposure of SH-SY5Y
      neuroblastoma and PC-12 cell lines to 6-OHDA increased the levels of free
      ubiquitin and ubiquitin-conjugated proteins, in a dose-dependent manner.
      Furthermore, metabolic labeling with 35S-methionine, demonstrated that 6-OHDA
      markedly increased protein degradation, as indicated by the secretion of protein
      metabolites to the medium. Inhibition of the proteasome activity by the specific
      inhibitor MG132, attenuated the protein degradation induced by 6-OHDA and
      potentiated its toxicity. Administration of the antioxidant N-acetylcysteine to
      the 6-OHDA-treated cells, increased cell survival and reduced protein
      degradation. In conclusion, our findings suggest that 6-OHDA toxicity is
      associated with protein degradation and ubiquitin-proteasome system activation.

PMID- 12043848
TI  - Genomic dissection reveals locus response to stress for mammalian
      acetylcholinesterase.
AB  - The mammalian acetylcholinesterase (ACHE) locus was investigated using
      computational predictive methods and experiments of reverse transcription
      polymerase chain reaction (RT-PCR). Computational analysis identified two genes
      downstream to ACHE, an inversely oriented arsenite resistance gene homologue
      (ARS), and a novel previously unidentified gene (PIX), co-oriented with ACHE.
      Experimental evidence shows coregulation of murine ACHE and ARS following
      confined swim, indicating coordinated locus response to stress, that is possibly
      mediated by altered cholinergic neurotransmission.

PMID- 12043850
TI  - Studies of sick building syndrome. IV. Mycotoxicosis.
AB  - There has been increasing public attention to the potential health risks of mold
      exposure, particularly in wet buildings. A variety of molds has been isolated
      from both damaged homes and businesses, including agents that secrete toxigenic
      materials. One area that is attracting particular notice is the relative
      toxigenic potential of mycotoxins. Although exposure to molds can produce
      significant mucosal irritation, there are very few data to suggest long-term ill
      effects. More importantly, there is no evidence in humans that mold exposure
      leads to nonmucosal pathology. In fact, many of the data on toxigenic molds are
      derived from animal toxicity studies, and these are based primarily, on
      ingestion. Although every attempt should be made to improve the quality of indoor
      air, including avoidance of molds, the human illnesses attributed to fungal
      exposure are, with the exception of invasive infections and mold allergy,
      relatively rare. In this review we discuss selected aspects of the microbiology
      of mycotoxin-producing molds and their potential role in human immunopathology
      with respect to wet building environments.

PMID- 12043849
TI  - Differential effects of the antipsychotics haloperidol and clozapine on G protein
      measures in mononuclear leukocytes of patients with schizophrenia.
AB  - AIMS: Heterotrimeric G proteins play a pivotal role in postreceptor information
      transduction. These proteins were previously implicated in the pathophysiology
      and treatment of mood and other neuropsychiatric disorders. Recently we showed
      that untreated patients with schizophrenia have a significantly elevated dopamine
      induced Gs protein function which is correlated with the severity of the
      psychotic symptoms. In contrast, an inverse picture with reduction in the
      function and the immunoreactivity of Gs protein was detected in patients with
      Parkinson's disease. The present study aims at investigating the effect of
      antipsychotic medications on dopamine-induced Gs protein hyperfunction in
      schizophrenia comparing the classical antipsychotic haloperidol and the newer
      antipsychotic clozapine, which is devoid of extrapyramidal side effects, on G
      protein measures. METHODS: G protein functional measurements coupled to beta
      adrenergic, muscarinic, and dopamine receptors were undertaken through bacterial
      toxin sensitive, agonist enhanced [3H]-Gpp(NH)p binding capacity, substantiated
      by quantitative measures of Gs alpha, Gi alpha, and G beta subunit proteins
      through immunoblot analysis in mononuclear leukocytes obtained from patients with
      schizophrenia under haloperidol, or clozapine treatments in comparison with
      untreated patients with schizophrenia and healthy volunteers. RESULTS: Dopamine
      induced Gs hyperfunction characteristic of untreated patients with schizophrenia
      was not detected under antipsychotic treatment with either haloperidol or
      clozapine. Haloperidol caused a significant decrease in Gs function and
      immunoreactivity below normal levels. The extend of reduction in Gs function was
      found to be correlated with the intensity of extrapyramidal side effects. The
      pattern of G protein subunits levels in patients with schizophrenia under
      haloperidol treatment resembles the one obtained in patients with Parkinson's
      disease. CONCLUSIONS: In the present study it is shown that G protein
      measurements in patients with schizophrenia under antipsychotic treatments can be
      used to biochemically monitor effects of antipsychotic medications in living
      patients. Moreover, these measurements may be used also for monitoring
      parkinsonian side effects induced by antipsychotic medications.

PMID- 12043851
TI  - Once-daily administration of budesonide Turbuhaler was as effective as twice
      daily treatment in patients with mild to moderate persistent asthma.
AB  - In a double-blind, randomized, placebo-controlled trial, 288 patients with mild
      to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs)
      were treated with budesonide Turbuhaler, 200 microg once every night (q.n.), 100
      microg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak
      expiratory flow (PEF) increased in both groups treated with budesonide but
      decreased in placebo-treated patients. Symptom scores and bronchodilator use were
      significantly reduced in both groups receiving active treatment (p = 0.023
      0.0001) compared with patients treated with placebo. There was no significant
      difference in outcome measurements between the two budesonide regimens. Thus,
      patients with mild to moderate persistent asthma receiving b.i.d. treatment with
      inhaled GCSs can usually be switched to budesonide Turbuhaler, 200 microg, q.n.
      without loss of asthma control.

PMID- 12043853
TI  - The decline of pulmonary function among patients with chronic asthma treated with
      inhaled corticosteroid.
AB  - We analyzed the rate of decline of pulmonary function annually over 2 years in 49
      patients with chronic asthma, who were being treated with inhaled corticosteroid
      (beclomethasone). The coefficient of linear regression of pulmonary function
      based on dose of inhaled corticosteroid may be used to track the exact rate of
      the decline of pulmonary function. The declining rate of pulmonary function is
      faster in the early stages of the disease, in spite of the treatment with inhaled
      beclomethasone. In chronic asthmatics, the distal airway units appear to
      deteriorate, and the extent of deterioration probably changes with the
      progression of the disease.

PMID- 12043852
TI  - The effect of cigarette smoking on the levels of nitric oxide metabolites in the
      sputum of patients with acute asthma.
AB  - Cigarette smoking may reduce the production of endogenous nitric oxide (NO),
      which plays an important role in inflammation of the asthmatic airway. NO
      metabolites in sputum were measured in 11 cigarette smokers and five nonsmokers,
      all with acute asthma. NO metabolite levels reflected the severity of asthmatic
      exacerbation, as they were significantly higher in patients with "severe," or
      "respiratory arrest imminent" asthma than in patients with "mild" to "moderate"
      asthma. There were no significant differences in sputum NO metabolite levels
      between smokers and nonsmokers with asthma, nor were any differences observed in
      NO metabolite levels for relative cigarette pack-years in smokers. These findings
      suggest that severe airway inflammation outweighs the effect of smoking on NO in
      the sputum of patients with asthma.

PMID- 12043854
TI  - Twice-daily budesonide inhalation suspension in infants and children < 4 and > or
      = 4 years of age with persistent asthma.
AB  - A retrospective analysis, based on a randomized, placebo-controlled, 12-week
      study in children 6 months to 8 years of age with persistent asthma, was
      performed to compare the efficacy and safety of budesonide inhalation suspension
      0.25 mg and 0.5 mg twice daily vs. placebo in children < 4 and > or = 4 years of
      age. Both age groups demonstrated significant (p < or = 0.050) improvement in
      nighttime and daytime asthma symptom scores and decreased bronchodilator use
      compared with placebo. In addition, the safety profile of twice-daily budesonide
      inhalation suspension was favorable in both age groups.

PMID- 12043855
TI  - The impact of in vivo Calmette-Guerin Bacillus administration on in vitro IgE
      secretion in atopic children.
AB  - To investigate whether a preexisting T helper (T(H)) 2 type immune response could
      be suppressed by Calmette-Guerin Bacillus (BCG) immunization in atopic children
      with asthma, we determined interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and
      IL-5 and total IgE level in the supernatant of peripheral blood mononuclear cells
      (PBMC) of six atopic and five nonatopic children in response to
      phytohemagglutinin A (PHA), purified protein derivate (PPD), and Dermatophagoides
      pteronyssinus II allergen (Der p II) both before and after BCG vaccination. IL-5
      level in response to Der p II was significantly higher in the atopic group than
      in the nonatopic group both before and after BCG vaccination (p = 0.004, p =
      0.009, respectively). In the atopic group, IgE levels determined in PPD and Der p
      II stimulated and unstimulated culture supernatants decreased significantly after
      BCG vaccination (p = 0.028, p = 0.026, p = 0.046, respectively), whereas in the
      nonatopic group (p = 0.041) BCG vaccination resulted in a significant decrease in
      IgE level only in response to Der p II stimulation. We concluded that in vivo BCG
      administration can downregulate both spontaneous and stimulated in vitro IgE
      secretion from PBMC of atopic children.

PMID- 12043856
TI  - Peripheral blood Th1 and Th2 profile in patients with moderate asthma: effect of
      inhaled corticosteroid.
AB  - The peripheral blood from healthy subjects and asthma patients was stimulated
      with phorbol 12-myristate 13-acetate and ionomycin, and the cells were stained
      with anti-CD4 antibody, permeabilized, stained with anti-IFN-gamma and anti-IL-4
      antibodies, and analyzed by flow cytometry. Compared with healthy subjects,
      asthma patients showed a greater percentage of both IL-4(+) IFN-gamma(-) CD4
      cells (Th2 cells) and IFN-gamma(+) IL-4(-) CD4 cells (Th1 cells). The percentage
      of Th2 cells was correlated with serum IgE level. After treatment with inhaled
      corticosteroid, Th2 cells decreased at week 24, but not week 4. Long-term therapy
      with inhaled steroid may thus be required for improvement in lymphocytic
      inflammation.

PMID- 12043857
TI  - Assessment of bronchial wall thickening on posteroanterior chest radiographs in
      acute asthma.
AB  - A central bronchus that is readily visible end-on in approximately 50% of normal
      frontal chest radiographs is the bronchus to the anterior segment of either upper
      lobe. Bronchial wall thickening, or "cuffing," is considered to be a radiographic
      sign of an asthmatic exacerbation and is cited as a useful sign in a number of
      leading textbooks; however, to the authors' knowledge, no prior chest
      radiographic study has quantitatively assessed this specific sign in a population
      of asthmatics suffering an acute exacerbation. Posterior chest radiographs were
      reviewed retrospectively for 51 nonasthmatic, nonsmoking control subjects and for
      45 adult asthmatic subjects during an acute exacerbation of moderate to severe
      asthma. Readers were blinded as to whether the radiograph was from an asthmatic
      or control subject. If visible end-on, the bronchus to the anterior segment of
      either upper lobe was assessed by measuring the diameter of the lumen and the
      thickness of the bronchial wall. At least one clearly defined bronchus to the
      anterior segment of an upper lobe was visible end-on in 22 patients (43%) in the
      control group and in 21 patients (47%) in the asthma group (p = NS). Mean wall
      thickness was 0.7 +/- 0.1 mm in the control group and 0.8 +/- 0.1 mm in the
      asthma group (p = 0.04). Lumen/wall thickness was 3.1 +/- 0.2 (SEM) in the
      control group and 2.5 +/- 0.2 in the asthma group (p = 0.055). The presence of
      bronchial wall thickness does not reliably distinguish radiographs of acutely
      asthmatic from normal individuals.

PMID- 12043858
TI  - Seasonal variations in hospital admissions for asthma in Malta.
AB  - The seasonality of asthma exacerbations may reflect varying exposure to triggers.
      This study retrospectively analyzes the seasonality of asthma hospital
      admissions, at all ages, in a population-based study. Analysis of the seasonality
      of asthma admissions and correlation with temperature was carried out in the
      setting of a regional hospital covering all acute asthma admissions in an island
      population. Admissions were divided into pediatric (1994-8) and adult (1989-8)
      cases. Both pediatric (0-14 years; n = 2916) and adult (15-59 years; n = 1269)
      admissions showed a peak in January and a trough in August. The seasonality in
      pediatric admissions was far more pronounced than in adults. Both cohorts
      exhibited a second, smaller peak in spring. In school-aged children, the end of
      school in June was associated with a sharp (91%) drop in admissions, and
      restarting school in October was associated with an even sharper rise (165%). A
      negative correlation was found between admissions and mean monthly ambient
      temperatures, and this was most pronounced in the pediatric age groups. This
      marked seasonality may indicate that temperature is a proxy for the total time
      spent indoors. Both the start and end of school had a profound impact on
      pediatric admission rates. Prospective studies are necessary to establish the
      role of viral infections and the influence of indoor and outdoor aeroallergens on
      the seasonality of hospitalization rates for asthma in the local setting.

PMID- 12043859
TI  - CD1a-positive cells in odontogenic cysts.
AB  - Langerhans cells (LC) are bone marrow-derived cells that have a CD1a-positive
      immunophenotype and are an important portion of the cell-mediated immune
      response. The aim of this study was an immunohistochemical evaluation of CD1a
      positive cells in different types of oral cysts. Fifty-five cysts were studied:
      18 odontogenic keratocysts (OKC), of which five were orthokeratotic and 13
      parakeratotic; 19 radicular cysts; and 18 dentigerous cysts. Positive LC was 80%
      for orthokeratotic OKC, 33% for parakeratotic OKC, approximately 35% for
      radicular cysts, and approximately 20% for dentigerous cysts. The results show
      that OKC with well-differentiated epithelial linings presented a greater number
      of LC than the other cysts. However, when the cyst wall was inflamed there were
      no differences in LC expression in the different types of cysts. The data confirm
      that LC distribution seems to be associated with the degree of differentiation of
      the epithelia.

PMID- 12043860
TI  - Microbial leakage evaluation of the continuous wave of condensation.
AB  - Coronal leakage has been recognized as a cause of pulpal and periradicular
      disease. Although cleaning and shaping of the root canal system is considered
      paramount, obturation of the system is an important step in endodontic success.
      The purpose of this study was to evaluate coronal bacterial leakage in teeth
      obturated with the System B continuous wave of condensation technique, followed
      by an Obtura II backfill, versus teeth obturated using the lateral condensation
      technique. Sixty single-rooted bilaterally matched teeth were evaluated in this
      study. An anaerobic bacterial leakage model was used. Results indicate that
      microbial coronal leakage occurs more quickly using lateral condensation than
      with the System B continuous wave of condensation and Obtura II backfill. This
      difference was statistically significant (p < or = 0.05). However, there was no
      statistical difference between groups 1 and 2 in the numbers of teeth that
      demonstrated bacterial leakage at the end of the study.

PMID- 12043861
TI  - Evaluation of leakage of bacteria and endotoxins in teeth treated endodontically
      by two different techniques.
AB  - Root canal recontamination occurs after contact between oral-bacterial flora and
      the coronal extremity of the root canal. The aim of this study was to evaluate
      the time required for endotoxins and bacteria to penetrate through root-canal
      obturations performed with vertical and lateral gutta-percha condensation
      techniques. Specimens prepared by the two alternative methods were exposed to
      contaminated saliva, and leakage into the root was evaluated over time. None of
      the obturated roots was infiltrated by endotoxins after 31 days. On the contrary,
      between day 13 and day 37 bacteria had infiltrated all specimens.

PMID- 12043862
TI  - Bacteriologic evaluation of the effect of Nd:YAG laser irradiation in
      experimental infected root canals.
AB  - The aim of this study was to evaluate the efficacy of the Pumped Diodium-Nd:YAG
      laser in sterilizing contaminated root canals. After hand instrumentation, 30
      teeth were inoculated with Actinomyces naeslundii CH-12 and 30 teeth with
      Pseudomonas aeruginosa ATCC 27853 and incubated for 24 h. The teeth were divided
      into three subgroups: subgroup A received no treatment; subgroup B was irradiated
      with laser (5 Hz for 15 s or 10 Hz for 15 s); and subgroup C was irrigated with
      5.25% NaOCl. The number of viable bacteria in each group was evaluated by using
      the surface-spread plate technique. The results indicated an average of 34.0%
      decrease in colony-forming units for A. naeslundii CH-12 and 15.7% for P.
      aeruginosa ATCC 27853 with the 5 Hz/15 s laser treatment, and for the 10 Hz laser
      frequency, a decrease of the 77.4% for A. naeslundii CH-12 and 85.8% for P.
      aeruginosa ATCC 27853. No bacteria were detected in the canals treated with 5.25%
      NaOCl. The results show an antibacterial effect of the Pumped Diodium Nd:YAG
      laser, depending on the radiation frequency. However, 5.25% NaOCl was more
      effective than either laser application.

PMID- 12043863
TI  - An optimal host response to a bacterium may require the interaction of leukocytes
      and resident host cells.
AB  - Bacterial infection results in inflammatory responses that may lead to soft
      tissue damage and bone resorption. However, the mechanisms by which different
      bacteria contribute to lesions of endodontic origin are not fully understood.
      This study examined the response to Streptococcus mutans and Porphyromonas
      endodontalis in two cell types that are involved in periapical pathology,
      mononuclear and osteoblastic cells. This was accomplished by measuring the
      induction of chemokines (monocyte chemoattractant protein-1, macrophage
      inflammatory protein-2) and proinflammatory cytokines (interleukin-1beta, tumor
      necrosis factor-alpha, interleukin-6, interferon-gamma). The results demonstrated
      that S. mutans more efficiently stimulate inflammatory cytokine production by
      mononuclear cells, whereas P. endodontalis is relatively more potent in
      activating osteoblastic cells. Moreover, optimal activation of osteoblastic cells
      by S. mutans requires soluble mediators produced by mononuclear cells, whereas P.
      endodontalis does not. These results suggest that the association of different
      bacteria with specific pathologic processes may be partially explained by their
      capacities to activate specific host cells.

PMID- 12043864
TI  - Canal-centering ability of two rotary file systems.
AB  - The ability of two nickel-titanium rotary file systems to maintain the original
      path of the canal were compared by using a new split-mold design (the Endodontic
      Cube). The mesial roots of 10 mandibular first- and second-molar teeth with
      separate canals from orifice to foramen were divided into two groups based on
      canal curvature and morphology. Working lengths for each canal were determined
      1.0 mm short of where the file tip was visible on the external surface of the
      root. The teeth were embedded in composite resin by using the Endodontic Cube as
      a mold and sectioned into five pieces. ProFile Ni-Ti.06 taper Series 29 and
      ProFile GT rotary instrumentation techniques were randomly assigned to one of the
      canals and used in a crown-down fashion to a 0.217 ProFile and a 0.06 GT master
      apical file, respectively. Digital photographs were made of the middle three
      sections and software features of Adobe Photoshop were used to measure the
      movement of the canal centers by superimposing the images of the instrumented and
      uninstrumented canals. Data were analyzed using ANOVA. Both systems remained
      centered within the canal with minimal deviation from the original canal path.
      The largest mean movement was less than 0.15 mm. The Endodontic Cube was an
      effective tool for studying and comparing instrumentation techniques.

PMID- 12043865
TI  - Effect of methotrexate-induced neutropenia on pulpal inflammation in rats.
AB  - The purpose of this study was to determine the role of neutropenia in pulpal
      inflammation. We investigated the effect of methotrexate-induced neutropenia on
      pulpal inflammation in rats. Pulpal inflammation was produced by pulpal exposure.
      Thirty-six rats were divided equally into control and experimental groups. The
      control animals received no injection, whereas the experimental animals were
      injected with 7.5 mg/kg of methotrexate once a day for 3 days before the pulpal
      exposure. The pulp was exposed in the mandibular first molar of all animals, and
      the exposed areas were left open. Animals were killed at 2, 4, and 7 days
      thereafter. Before they were killed, peripheral blood was taken. The number of
      total leukocytes and neutrophils in the peripheral blood of experimental animals
      was significantly decreased compared with those of control animals. The
      methotrexate-induced neutropenia resulted in the initiation of a bacterial
      invasion into the pulpal tissue and an increase in pulpal necrosis, as well as
      lessened abscess formation. Histometrically, the area of pulpal necrosis in
      experimental animals was significantly greater than that in the control animals.
      Immunohistochemically, the neutropenia resulted in inhibition of the infiltration
      by neutrophils. These results suggest that the neutrophil plays an important role
      in the defense against bacteria in pulpal tissue.

PMID- 12043866
TI  - Resinous perforation-repair materials inhibit the growth, attachment, and
      proliferation of human gingival fibroblasts.
AB  - The choice of repair material is one of the important factors in the prognosis of
      the endodontically treated tooth with a perforation defect. The cytotoxicity of
      perforation-repair materials must be investigated to ensure a safe biological
      response. The aim of this in vitro study was to evaluate the effect of resin
      modified, glass-ionomer cement, compomer, and resin on human-gingival
      fibroblasts. Human gingival fibroblasts from crown lengthening surgery were
      cultured by using an explant technique with the consent of the patient.
      Cytotoxicity was judged by using an assay of tetrazolium bromide reduction. The
      results showed that resin-modified, glass-ionomer cement Fuji II LC, compomer
      Compoglass, and resin SpectrumTPH (TPH) were cytotoxic to primary human gingival
      fibroblast cultures by inhibiting cell growth and proliferation. TPH alone had an
      effect on cell attachment. It was found that TPH was the most cytotoxic repair
      material among those tested in all cultures. The toxicity decreased in the order
      of TPH>FLC>CG.

PMID- 12043867
TI  - Effect of irrigating solution and calcium hydroxide root canal dressing on the
      repair of apical and periapical tissues of teeth with periapical lesion.
AB  - The objective of this study was to evaluate the apical and periapical repair
      after endodontic treatment of teeth with pulp necrosis and a chronic periapical
      lesion in dogs. Seventy-two root canals from four mongrel dogs were submitted to
      biomechanical preparation, using 5.25% sodium hypochlorite or 2% chlorhexidine
      digluconate as the irrigating solution. The root canals were subsequently either
      filled immediately with Sealapex, using active lateral gutta-percha condensation,
      or a calcium hydroxide root canal dressing was applied for 15 days before filling
      with Sealapex. After 210 days, the animals were killed by anesthetic overdose,
      and the obtained histological sections were stained with hematoxylin and eosin
      for optical microscopic analysis of apical and periapical repair. There was
      better histological repair in the groups with the root canal dressing (p < 0.05)
      than the groups with immediate obturation. Comparing the immediate obturation
      groups, irrigation with chlorhexidine solution resulted in better repair than
      sodium hypochlorite.

PMID- 12043868
TI  - Evaluation of Glyde File Prep in combination with sodium hypochlorite as a root
      canal irrigant.
AB  - The purpose of this study using a scanning electron microscope was to investigate
      the efficacy of four different irrigation techniques after canal preparation with
      Profile Ni-Ti rotary instruments. A modified technique for the use of Glyde File
      Prep is proposed. Forty anterior teeth were divided into four groups,
      instrumented, and irrigated as follows: physiological solution (group A), 2.5%
      sodium hypochlorite (group B), 2.5% sodium hypochlorite and Glyde File Prep
      (group C), and 2.5% sodium hypochlorite and Glyde File Prep applied at the end of
      the preparation with sterile paper points (group D). After scanning electron
      microscopic evaluation at three different levels, debris, smear layer, and
      dentinal tubules were scored. Groups A and B had significantly more smear layer
      and less open tubules on the canal walls compared with the group C and group D
      samples. Differences in the mean amount of debris between group A samples and
      other irrigation regimes were statistically significant.

PMID- 12043869
TI  - Microbiota of periapical lesions refractory to endodontic therapy.
AB  - The periapical microbiota of 36 teeth with refractory apical periodontitis was
      investigated. None of the teeth had responded to conventional endodontic or long
      term (> 6 months), calcium-hydroxide treatment. Eight patients had received
      antibiotics systemically. After anaerobic culture, a total of 148 microbial
      strains were detected among 67 microbial species. One of the 36 lesions was
      culture-negative. Approximately half (51.0%) of the bacterial strains were
      anaerobic. Gram-positive species constituted 79.5% of the flora. Facultative
      organisms, such as Staphylococcus, Enterococcus, Enterobacter, Pseudomonas,
      Stenotrophomonas, Sphingomonas, Bacillus, or Candida species were recovered from
      27 of the lesions (75%). Sulfur granules were found in 9 lesions (25%). In these
      granules Actinomyces israelii, A. viscosus, A. naeslundii, and A. meyeri were
      identified. Other bacterial species, both gram-positive and gram-negative, were
      detected in the granules as well. Two sulfur granules did not contain
      Actinomyces. Scanning electron microscopy demonstrated rod- and spirochete-like
      cells in the granules, and transmission electron microscopy revealed organisms
      with copious amounts of extracellular material. Outer membrane vesicles were also
      seen. Some of the granules were calcified. This study demonstrated a wide variety
      of microorganisms, particularly gram-positive ones, in the periapical lesions of
      teeth with refractory apical periodontitis.

PMID- 12043870
TI  - The effect of instrumentation with two different file types, each with 2.5% NaOCl
      irrigation on the microhardness of root dentin.
AB  - The aim of this study was to measure root-dentin microhardness after
      instrumentation with two types of files and using irrigation with 2.5% sodium
      hypochlorite. Thirty roots were instrumented with irrigation: 10 roots had the
      pulp extirpated only; 10 roots were instrumented with stainless steel files, and
      10 roots were instrumented with rotary nickel-titanium (NiTi) files.
      Additionally, five roots were extirpated only without irrigation and served as a
      control. The roots were sliced and root-dentin microhardness was determined at
      depths of 500 microm and 1000 microm from the pulp-dentin interface. Significant
      differences were found between the microhardness at 500 microm and 1000 microm (p
      < 0.001) in all groups. Instrumentation with NiTi rotary files affected dentin
      microhardness significantly to a lesser extent.

PMID- 12043871
TI  - Tissue levels of matrix metalloproteinases in pulps and periapical lesions.
AB  - The purpose of this study was to evaluate the tissue levels of matrix
      metalloproteinase (MMP)-1, -2, -3 and their distributions in inflamed human
      dental pulps and periapical lesions. Samples were subjected to enzyme-linked
      immunosorbent assay and/or immunohistochemistry by using specific antibodies to
      MMP-1, -2, and -3. Results from enzyme-linked immunosorbent assay were analyzed
      by using the Mann-Whitney U test and presented as p values. The concentrations of
      MMP-1 in all experimental groups were significantly higher than in the control (p
      < 0.05). The acute pulpitis and control groups were significant different in
      terms of their MMP-2 levels (p < 0.05). The concentration of MMP-3 in acute
      pulpitis was significantly higher than the control and chronic pulpitis groups (p
      < 0.05). Immunohistochemically, MMP-1 and MMP-3 were localized in the
      infiltrating neutrophils, macrophages, and extracellular matrix of the acute
      pulpitis group. These results suggest that MMPs play an important role in the
      pulp tissue destruction of acute, inflamed pulp.

PMID- 12043872
TI  - A comparison of shaping ability using ProFile, GT file, and Flex-R endodontic
      instruments in simulated canals.
AB  - A total of 160 resin-simulated canal blocks with 20-degree or 30-degree curvature
      were prepared by ProFile rotary instruments, GT rotary files, and the balanced
      force technique with Flex-R files. Using an image analysis computer application,
      the pre- and postoperative images were stored and superimposed, and then the
      amount of material removed from the preoperative inner and outer curved walls was
      measured at five levels in the apical 5 mm of the canal. The time required for
      canal preparation, including irrigation, and the time taken to change instruments
      was recorded. At 1 mm from the apical end, the directions of canal transportation
      were most frequently toward the outer aspect of the curvature, with the only
      exception being the canals shaped by the balanced force technique in which more
      was removed from the inner aspect. The balanced force technique required more
      preparation time than the rotary instrumentation.

PMID- 12043873
TI  - Hemostatic efficacy and cardiovascular effects of agents used during endodontic
      surgery.
AB  - The hemostatic efficacy, as well as the cardiovascular effects, of two hemostatic
      agents currently used during endodontic surgery was examined. The hemostatic
      agents used were epinephrine pellets (Racellet pellets) or 20% ferric sulfate
      (Viscostat). Patients were assigned to one of two experimental groups. Blood
      pressure and pulse rate were recorded pre- and postoperatively and at three
      additional times during the surgery (root-end resection, root-end preparation,
      and filling). The adequacy of hemostasis was rated by the surgical operator.
      Results indicated that there is no significant change in cardiovascular effects
      when using either of these hemostatic agents. Except in one case where ferric
      sulfate was the agent, both agents produced surgical hemostasis that allowed for
      a dry field for root-end filling.

PMID- 12043874
TI  - Effect of magnification on locating the MB2 canal in maxillary molars.
AB  - The purpose of this study was to determine if the surgical operating microscope
      and/or dental loupes could enhance the practitioner's ability to locate the
      second mesiobuccal canal (MB2) canal of maxillary molars in an in vivo, clinical
      setting. The participating endodontists documented 312 cases of root canal
      therapy on maxillary first and second molars. Participants that used the
      microscope or dental loupes located the MB2 canal with a frequency of 57.4% and
      55.3%, respectively. Those using no magnification located the MB2 canal with a
      frequency of 18.2%. When no magnification was used, significantly fewer MB2
      canals were located based by Chi-square analysis at p < 0.01. There was no
      significant difference between the use of the microscope and dental loupes in the
      frequency of locating the MB2 canal. When the maxillary first molars were
      considered separately, the frequency of MB2 canal detection for the microscope,
      dental loupes, and no magnification groups was 71.1%, 62.5%, and 17.2%,
      respectively. The results of this study show that the use of magnification in
      combined groups leads to a MB2 detection rate approximately three times that of
      the nonmagnification group and that the use of no magnification results in the
      location of significantly fewer MB2 canals. Based on these results, more emphasis
      should be placed on the importance of using magnification for locating the MB2
      canal.

PMID- 12043876
TI  - Root-end fracture during retropreparation: a comparison between zirconium nitride
      coated and stainless steel microsurgical ultrasonic instruments.
AB  - The purpose of this study was to evaluate a stainless steel (CT-5) and zirconium
      nitride coated (KiS) microsurgical ultrasonic instrument with regard to possible
      root-end fracture production during retropreparation. Forty extracted human
      central incisors were prepared in a crown-down fashion. Canals were obturated
      with gutta-percha by lateral condensation. Root-ends were resected. Teeth were
      placed in methylene blue for 48 h and evaluated by three independent evaluators
      under microscope. Teeth with existing fractures were eliminated from the study.
      The remaining teeth were randomly divided into two equal groups. Group A was
      prepared with the CT-5 tip and Group B with the KiS tip. Preparation time was
      recorded for all roots. The teeth were again immersed in methylene blue for 48 h
      and reevaluated. No root-end fractures were produced by either the KiS or CT-5
      microsurgical ultrasonic instruments.

PMID- 12043875
TI  - Leakage of interim post and cores used during laboratory fabrication of custom
      posts.
AB  - The aim of this study was to compare coronal microleakage in two conditions.
      Twenty-eight extracted upper molars were endodontically treated and divided into
      two groups and controls: group A: prefabricated post and core permanently
      cemented; and group B: prepared for a post and restored with a temporary post
      crown cemented with a temporary cement. The teeth were thermocycled, immersed in
      black India ink for 1 week, and made transparent. Results indicated that the
      permanently cemented, prefabricated post and core produced the best seal (p <
      0.01); leakage was significantly greater with the temporary post crown and was
      similar to that of a positive control group.

PMID- 12043877
TI  - Apical pressures developed by needles for canal irrigation.
AB  - Drying instrumented canals with pressurized air may result in patient morbidity
      or even fatality. Low pressure and side vent needles have been suggested to
      lessen the danger. This study observed apical pressures from different needles
      inserted deeply into small round and ovoid canals as instrumentation progressed.
      Low-pressure (5 psi) air was injected through the needles, and apical pressures
      were recorded after each instrument. Pressures varied greatly within each test
      group. Generalities that can be drawn are that binding the needle within the
      canal gives higher pressures than with the needle slightly short of binding and
      that pressures were higher with apexes instrumented to size 30 and higher. With
      the needle tightly bound, neither needle size, needle design, nor canal shape
      resulted in statistically significant mean pressure differences. With the needle
      slightly withdrawn, larger bore needles gave higher pressures than small diameter
      needles. Caution is advised with the clinical use of pressurized air in the
      drying of root canals.

PMID- 12043878
TI  - Microscopic removal of dens invaginatus.
AB  - Endodontic treatment for teeth that exhibit the dental anomaly, dens invaginatus,
      can be difficult due to the bizarre anatomy and relative inaccessibility of the
      diseased pulp tissue. Surgical intervention or extraction are common approaches
      to dealing with this condition. This article reports the treatment of an extreme
      form of dens invaginatus, employing the dental-operating microscope and the
      ultrasonic instrument. Removal of the entire anomalous structure and pulp tissue
      was possible, and conventional orthograde obturation was accomplished. Two and 4
      yr follow-up radiographs show that healing has occurred. The article demonstrates
      that the anomalous structure of dens invaginatus is a separate entity from the
      rest of the tooth. This implies that in many instances it may be entirely removed
      to facilitate conventional endodontic therapy.

PMID- 12043879
TI  - Zebra XXIV, part 2.

PMID- 12043880
TI  - Evidence-based endodontics: what does it mean for our profession and the AAE?

PMID- 12043881
TI  - ENA: its place in medicine.

PMID- 12043882
TI  - Shwartzman phenomenon in a patient with active systemic lupus erythematosus
      preceding fatal disseminated intravascular coagulation.
AB  - The recurrence of widespread and diverse vascular lesions is a hallmark of
      systemic lupus erythematosus (SLE). Inflammatory and thrombotic mechanisms almost
      invariably associated with circulating antiphospholipid antibodies play a role in
      the pathogenesis of SLE-related vascular disease. Both mechanisms can coexist in
      the same patient. Vasculitis is most commonly induced by the local deposition of
      immune complexes. However, some SLE patients have an inflammatory complement
      mediated vascular injury in the absence of immune complex deposition. We report
      on a fatal case of disseminated intravascular coagulation (DIC) in a young woman
      with active SLE. Hemorrhagic lesions due to localized intravascular coagulation
      (Shwartzman phenomenon) preceded disseminated intravascular coagulation
      accompanied by disseminated cardiac necrosis. Immune complex 'independent' and
      other mechanisms of vascular injury and states of hypercoagulability will be
      discussed.

PMID- 12043883
TI  - Anticardiolipin antibody titre and plasma homocysteine level independently
      predict intima media thickness of carotid arteries in subjects with idiopathic
      antiphospholipid antibodies.
AB  - This study evaluated whether IgG anticardiolipin antibody (aCL) titre and
      traditional risk factors for atherosclerosis bore any relationship to the intima
      media thickness (IMT) of carotid arteries of patients with idiopathic
      antiphospholipid antibodies (aPL). IMT was assessed by high-resolution sonography
      at the common carotid, carotid bifurcation and internal carotid in 42 (13 male,
      29 female, mean age 31+/-10 years) aPL subjects, 29 with primary thrombotic
      antiphospholipid syndrome and 13 with persistence of aPL in the absence of any
      underlying disorder. In the same subjects the following were measured: plasma
      fibrinogen (FNG), von Willebrand factor (vWF), plasminogen activator inhibitor
      (PAI), homocysteine (HC), total cholesterol (CHO), triglycerides (TG), high
      density and low density lipoprotein (HDL and LDL), platelet numbers and aCL of
      IgG and IgM isotype. IMT of the internal carotid was greater in males than
      females (0.48+/-0.03 vs 0.39+/-0.01 mm, P=0.02). IMT of the carotid bifurcation
      was greater in thrombotic than nonthrombotic subjects (0.50+/-0.02 vs 0.42+/-0.02
      mm, P=0.04). By simple regression, IMT of the common carotids correlated with age
      (P< 0.0001) IgG aCL titre (P=0.001), FNG (P=0.006), LDL (0.01), CHO (0.02) and
      PAI (P=0.02). IMT of the carotid bifurcation correlated with age (P=0.002), IgG
      aCL titre (P=0.0002), FNG (P=0.0001), HC (P=0.009), CHO (P=0.02), vWF (P=0.01)
      and number of thrombotic events (P=0.03). IMT of the internal carotids correlated
      with age (P=0.002), IgG aCL titre (P=0.0001), FNG (P=0.0008), PAI (P=0.002) and
      HC (P=0.01). By stepwise multiple regression analysis, IgG aCL titre
      independently predicted IMT at all carotid segments examined (P always <0.005).
      In addition, plasma FNG and HC also resulted independent predictors of IMT at the
      carotid bifurcation (P=0.001 and P<0.0001, respectively) and internal carotid
      (P=0.03 and P<0.0001, respectively). These data strongly support an atherogenic
      role for IgG aCL in patients with aPL. Measurement of plasma HC and FNG may help
      define aPL subjects at higher vascular risk who may require lowering of HC and
      FNG by vitamin and/or pharmacologic intervention.

PMID- 12043884
TI  - Dual antibody reactivity to beta2-glycoprotein I and protein S: increased
      association with thrombotic events in the antiphospholipid syndrome.
AB  - The antiphospholipid syndrome (APS) is a thrombotic disorder leading to
      spontaneous abortions, venous thromboses, myocardial infarctions and strokes.
      Although the syndrome is associated with characteristic autoantibodies, these
      tests have poor predictive value for thrombosis. The aim of the study was to
      determine whether the combined presence of two types of antiphospholipid
      antibodies can be associated with a high-risk subset of thrombosis-prone
      patients. One hundred and thirty-four sera from a lupus clinic were tested for
      antibodies to beta2-glycoprotein I (beta2GPI), protein S and prothrombin. In a
      group of 29 patients for whom plasma was available, free (functional) protein S
      levels were also measured. Autoantibodies to beta2GPI and protein S are
      associated with each other. Dual reactivity to beta2GPI and protein S correlates
      with increased history of thrombotic events (69% of doubly reactive patients)
      when compared to either type of autoantibody alone (37% of patients with only
      anti-beta2GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively)
      or neither reactivity (37%). Among 29 patients tested for free (functional,
      anticoagulant) protein S levels, the lowest levels were found in patients with
      antibodies to beta2GPI and/or protein S, and all four patients with a history of
      thrombosis had below-normal free protein S levels. These associations were not
      found with antiprothrombin antibodies. In conclusion dual autoantibodies to
      beta2GPI and protein S are associated with increased history of thrombosis in the
      antiphospholipid syndrome.

PMID- 12043885
TI  - Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus
      erythematosus.
AB  - Thrombocytopenia is a common phenomenon in patients suffering from systemic lupus
      erythematosus (SLE). The cause of thrombocytopenia in SLE, however, is poorly
      understood. In this study, 100 patients with SLE were evaluated for serum
      thrombopoietin levels, anti-thrombopoietin antibodies and routine laboratory
      parameters such as peripheral blood counts, parameters of blood chemistry and
      immunologic parameters of SLE. The median platelet count of SLE patients was 230
      g/l and 19 were thrombocytopenic (range 8-148 g/l). Thrombopoietin levels in SLE
      patients were found to be significantly higher than in healthy controls (n = 96;
      median, 117 pg/ml vs 64 pg/ml, P < 0.01). When excluding thrombocytopenic SLE
      patients, thrombopoietin levels in SLE were still above controls (111 pg/ml, P <
      0.01). The thrombopoietin levels were correlated to erythrocyte sedimentation
      rate and ECLAM score of disease activity, and inversely correlated to complement
      factor C4, but not to the platelet count. Anti-thrombopoietin antibody reactivity
      was found in 23% of SLE patients. Interestingly, these patients had lower
      platelet counts than SLE patients without anti-thrombopoietin antibodies (median
      174 g/l and 253 g/l, respectively, P < 0.01), but thrombopoietin levels were not
      significantly different. Taken together, thrombopoietin levels are significantly
      higher in the sera of SLE patients than in healthy controls and anti
      thrombopoietin antibodies are frequently found.

PMID- 12043886
TI  - Angiotensin-converting enzyme gene polymorphism and vascular manifestations in
      Korean patients with SLE.
AB  - Systemic lupus erythematosus (SLE) is an inflammatory multisystem disease of
      unknown etiology with immunologic aberrations. Many studies have shown that
      genetic and environmental factors are implicated in the development of SLE.
      Angiotensin-converting enzyme (ACE) affects various immune phenomena through the
      renin-angiotensin and kallikrein-kininogen systems by creating angiotensin II and
      inactivating bradykinin. We investigated the correlation between insertion/
      deletion polymorphism of the ACE gene and the clinical manifestations of SLE,
      especially vascular involvement and lupus nephritis. Two-hundred and eleven
      Korean patients fulfilling the ACR criteria and 114 healthy subjects were
      enrolled. The ACE genotype was determined by polymerase chain reaction using
      genomic DNA from peripheral blood. The nephritis patients were classified by the
      WHO classification. In addition, the activity and chronicity index were used to
      assess the severity of renal involvement. We evaluated vascular involvement by
      the presence or absence of hypertension, Raynaud's phenomenon, livedo
      reticularis, antineutrophil cytoplasmic antibody and the SLICC/ACR Damage Index.
      The gene frequency of ACE gene polymorphism was as follows: II 39 vs 34%, ID 41
      vs 50%, DD 20 vs 16% in SLE patients and controls, respectively. There was no
      difference in genotype frequency between both groups. There were no significant
      differences between the distribution of ACE gene genotypes and lupus nephritis
      and its related parameters, including WHO classification, activity index,
      chronicity index, renal dysfunction and amount of 24 h urinary protein. The ACE
      genotypes and alleles did not affect the presence of vascular manifestations
      evaluated, but the frequency of DD genotype was significantly low in SLE patients
      with Raynaud's phenomenon compared to those without Raynaud's phenomenon (P =
      0.002 for ACE ID vs DD and II, OR 2.7, 95% CI 1.43-5.09; P=0.023 for ACE DD vs ID
      and II, OR 0.33, 95% CI 0.12-0.89). Also skewing from DD to II genotype was noted
      in patients with anti-Sm antibody compared to those without anti-Sm antibody (P =
      0.025 for ACE DD vs ID and II, OR 0.21, 95% CI 0.05-0.93). The onset age of
      serositis was older in patients with the ID genotype than the others (ID= 34.5+/
      10.8, II + DD = 25.6+/-10.2, P= 0.002). Also the onset age of malar rash was
      older in patients with II genotype than the others (II=26.7+/-8.4, ID+DD=21.3+/
      9.0; P=0.021). The patients with I allele showed a significantly higher frequency
      of serositis (P = 0.022). Taken together, the I/D polymorphisms of ACE gene did
      not affect susceptibility of SLE, lupus nephritis and the vascular
      manifestations, including Raynaud's phenomenon, in Korean SLE patients, although
      the DD genotype was negatively associated with Raynaud's phenomenon among SLE
      patients. However, it would be valuable to evaluate the role of other genes
      potentially related to vascular events, such as endothelin, nitric oxide or
      angiotensin II receptor as well as ACE gene.

PMID- 12043887
TI  - The nature and outcome of infection in systemic lupus erythematosus.
AB  - Infection remains a major cause of morbidity and mortality in systemic lupus
      erythematosus (SLE). To describe the nature and outcomes of infection and
      determine their associated risk factors in patients with SLE, we performed a
      nested case-control study at the University of Toronto Lupus Clinic, with
      prospective follow-up according to a standard protocol since 1970. Cases were SLE
      patients seen between January 1987 and January 1992 who had documented infections
      and controls were patients without infection from the same cohort matched for
      age, gender and time of visit. The type, site and outcome of infection were
      recorded for each case. A conditional logistic regression analysis was performed
      to compare factors associated with infection in cases and their controls. Ninety
      three patients had 148 infection episodes; the majority were bacterial, but
      viral, fungal and protozoan organisms were also identified (multiple organisms in
      seven). Forty-eight patients required hospital admission and three patients died.
      Steroids at time of infection, as well as use ever, duration and dose,
      immunosuppressives at time of infection and use ever, active renal disease, CNS
      damage, SLEDAI at the time of infection, adjusted mean SLEDAI and variability
      measure were significantly associated with infection by univariate analysis. By
      multivariate analysis one factor remained statistically significant: use of
      steroids ever (P = 0.029). Infection carries a large burden for SLE patients.
      Until new medications which will control disease activity without predisposing to
      infection are developed, careful titration of steroids and cytotoxic drugs to
      control disease activity will remain crucial.

PMID- 12043888
TI  - Fcgamma and complement receptors: expression, role and co-operation in mediating
      the oxidative burst and degranulation of neutrophils of Brazilian systemic lupus
      erythematosus patients.
AB  - We have investigated the individual role of FcgammaR and CR, as well as their
      cooperation, in mediating the oxidative burst and degranulation of neutrophils of
      Brazilian systemic lupus erythematosus (SLE) patients. Neutrophils were
      stimulated with the immune complexes (IC)-IgG or -F(ab')2, opsonized or not with
      normal or SLE human serum. The oxidative burst was decreased in neutrophils of
      active SLE patients compared to healthy controls when this response was mediated
      by FcgammaR and/or CR, while the degranulation was unaffected. The SLE
      hypocomplementemia did not affect the oxidative burst mediated only by CR.
      FcgammaRII and CR1 expression on neutrophils of active SLE patients was reduced,
      while the expression of FcgammaRIII and CR3 was unaffected. These results suggest
      that the different FcgammaR and CR may be involved or cooperate in different ways
      in the mediation of the oxidative burst and the degranulation. Moreover, the
      decreased oxidative burst of neutrophils of active SLE patients may not depend
      only on SLE hypocomplementemia for IC opsonization. These observations are
      directed at the understanding of how each of these immune system components
      (FcgammaR, CR and complement) influences the precise biological neutrophil
      responses both in physiological and pathological conditions. Since the Brazilian
      population comprises many races, these results are important because they are
      directed at a specific population of SLE patients.

PMID- 12043889
TI  - Mycobacterium haemophilum infection in an SLE patient on mycophenolate mofetil.
AB  - We describe a case of Mycobacterium haemophilum in an immunocompromised patient
      with systemic lupus erythematosus (SLE). Mycobacterium haemophilum is a recently
      described pathogen which has not been previously described either in SLE patients
      or patients on Mycophenolate Mofetil. Mycobacterium haemophilum can be difficult
      to diagnose, as it may not have the granulomas characteristic of atypical
      mycobacterial infections. Combination therapy with at least two drugs for several
      months is required and the outcome depends on the patient's underlying
      immunocompromised state. Our report highlights the need for early diagnosis and
      treatment of Mycobacterium haemophilum in immunocompromised patients with SLE.

PMID- 12043890
TI  - Hypertension as the presenting feature of the antiphospholipid syndrome.
AB  - The antiphospholipid or Hughes syndrome is the association between
      antiphospholipid antibodies (aPL), venous and arterial thromboses and pregnancy
      morbidity. Antiphospholipid syndrome (APS) commonly coexists with autoimmune
      diseases usually systemic lupus erythematosus (SLE), when it is known as
      secondary APS. When present in isolation it is known as primary APS (PAPS).
      Although the kidney may be affected in APS, its involvement is perhaps not as
      well described as that of other organs. Thrombotic microangiopathy (TMA)
      affecting the kidney has been reported as a manifestation in both primary and
      secondary APS. This report describes hypertension related to underlying renal TMA
      as a presenting symptom of APS.

PMID- 12043891
TI  - Ultraviolet light exposure is not a requirement for the development of cutaneous
      neonatal lupus.
AB  - Cutaneous neonatal lupus erythematosus (NLE) is a rare disorder, linked to the
      presence of transplacentally acquired maternal autoantibodies (anti-ENA). NLE
      skin lesions frequently appear in the second or third month of life, and
      ultraviolet exposure is thought to be an initiating factor since it can
      externalize intranuclear autoantigens at the cell surface. We report a baby who
      was born already with an extensive NLE rash, suggesting that sun exposure is not
      a requirement for the development of NLE skin lesions. A 31-year-old woman
      affected with mixed connective tissue disease gave birth to a female after 38
      weeks of gestation. Pregnancy was uneventful and no perinatal complications were
      seen. The mother was positive for anti-RNP, but negative for anti-SSA/Ro and
      SSB/La autoantibodies. Already at birth, an extensive scarring rash with a few
      erythematosus lesions was present on the baby's face and scalp; this progressed
      over the following months, and subsequently stabilized. Anti-RNP were present in
      the baby's serum. Due to the unusual features of the disease expression, a skin
      biopsy was performed at age 5 months; results were consistent with the diagnosis
      of NLE, showing mononuclear cell infiltration and immunoglobulin deposition. No
      other features of NLE were detected. This observation is unusual for: (1) the
      presence of an NLE rash in the absence of anti-SSA/Ro; (2) the scarring and
      atrophic characteristics of the lesions; and (3) the development already in
      utero. This latter finding argues against sun exposure being necessary for lesion
      induction.

PMID- 12043892
TI  - The SLICC damage index: past, present and future.

PMID- 12043893
TI  - Treatment of systemic lupus erythematosus with bromocriptine.

PMID- 12043894
TI  - Democratizing the hospital: deliberative-democratic bioethics.
AB  - The increased presence of moral consultants, or bioethicists, within hospitals
      and clinics in the last two decades has begun to raise questions about their
      sources of authority and norms of practice. Under pressure from critics in the
      social sciences, a number of bioethicists have recently raised the ideal of
      democratic deliberation to defend and reconstruct their place in the medical
      field. This article sheds light on these developments by placing bioethics in a
      historical context that shows an early tension between bioethicists as whistle
      blowers and bioethicists as incremental reformers of medical practice. This
      article also develops a conceptual framework for analysis that indicates how such
      tensions have grown more complicated for contemporary bioethicists because they
      occupy a fluid and structurally ambiguous role in which there are multiple
      sources of normative expectations and little guidance for meeting these
      expectations. The liminality of the role and the overload of expectations have
      made bioethics vulnerable to methodological criticisms from social scientists.
      This article concludes that such methodological criticisms cannot address the
      more systemic problems of liminality and overload. The ideal of democratic
      deliberation, though imperfect, does address these systemic problems because it
      shows bioethicists how to gain guidance and share responsibility for moral
      consultation.

PMID- 12043895
TI  - Courts and health policy: judicial policy making and publicly funded health care
      in Canada.
AB  - The 1982 Canadian Charter of Rights and Freedoms provided political actors with
      the opportunity to make rights-based challenges to public policy decisions. Two
      challenges launched by providers and consumers of health care illuminate the
      impact of judicial review on health care policy and the institutional capacity of
      courts to formulate policy in this field. The significant impact of rights-based
      claims on cross-jurisdictional policy differences in a federal regime is noted.

PMID- 12043896
TI  - Terrorism, guns, and public health.

PMID- 12043897
TI  - Preventing lethal violence in schools: the case for entry-based weapons
      screening.
AB  - Violence-related behavior in schools has declined in recent years, but the
      perception of risk remains high. Disturbingly high percentages of students and
      teachers report staying home out of fear, and many students bring weapons to
      school for protection. Current proposals for preventing school violence include
      punishing the violence-prone, expulsion for weapon carriers, and creating a
      culture of nonviolence through various behavioral methods like conflict
      resolution. None of these proposals address the issue of lethal violence and
      hence personal safety. The risk of lethal violence in schools (related mainly to
      firearms) could be substantially reduced by creating an effective barrier between
      firearms and people. This could be achieved by using entry-based weapons
      detection systems similar to those now used in airports and courts. Decreasing
      the risk and fear of violence by converting schools into weapons-free zones would
      also be expected to increase attendance and improve scholastic performance.
      Randomized, controlled studies should be undertaken to evaluate the efficacy and
      cost-effectiveness of entry-based weapons detection systems for achieving these
      outcomes.

PMID- 12043898
TI  - Is a weapons-screening strategy for public schools good public policy?

PMID- 12043899
TI  - Lethal violence in the schools.

PMID- 12043900
TI  - Responding to chemical, biological, or nuclear terrorism: the indirect and long
      term health effects may present the greatest challenge.
AB  - The possibility of terrorists employing chemical, biological, or nuclear/
      radiological (CBN) materials has been a concern since 1995 when sarin gas was
      dispersed in a Tokyo subway. Contingency planning almost exclusively involved
      detection. containment, and emergency health care for mass casualties. However,
      it is clear that even small-scale CBN incidents--like the recent spread of
      anthrax spores through the mail--can cause widespread confusion, fear, and
      psychological stress that have lasting effects on the health of affected
      communities and on a nation's sense of well-being. More emphasis therefore needs
      to be placed on indirect effects and on the medical, social, economic, and legal
      consequences that follow months to years afterward. To respond effectively to CBN
      attacks, a comprehensive strategy needs to be developed that includes not only
      emergency response, but also long-term health care, risk communication, research,
      and economic assistance. Organizing an effective response challenges government
      institutions because the issues involved--eligibility for health care, the
      effects of low-level exposure to toxic agents. stress-related illnesses,
      unlicensed therapeutics. financial compensation--are complex and controversial.

PMID- 12043901
TI  - On the use of age-adjusted mortality rates in studies of income inequality and
      population health.

PMID- 12043902
TI  - Singapore's medical savings accounts--beyond rhetoric and doctrine to "what
      works": a response from Singapore.

PMID- 12043903
TI  - The role of Tc-99m sestamibi imaging in predicting clinical response to
      chemotherapy in lung cancer.
AB  - Multidrug resistance (MDR) is a major problem in lung cancer. Tc-99m
      methoxyisobutyl isonitrile (MIBI) has been demonstrated to be a non-invasive
      marker to diagnose MDRI related P-glycoprotein (Pgp) and multidrug resistance
      associated protein (MRP) expression in various solid tumors. The aim of this
      study was to evaluate the relationship between the degree of Tc-99m MIBI uptake
      and its retention on delayed images and the response to chemotherapy in lung
      cancer. Twenty-three patients (1 woman and 22 men, age range 40-67 years) with
      lung cancer (9 small cell and 14 non-small cell) were examined with Tc-99m MIBI
      imaging before chemotherapy. After i.v. administration of 740 MBq Tc-99m MIBI,
      planar and SPECT imaging at 30 minutes and 2 hours was performed. Tumor to normal
      lung uptake ratio (T/N) and percent retention were measured. Response to
      chemotherapy was evaluated according to follow-up CT and grouped as complete
      responders (CR), partial responders (PR) and non-responders (NR). Clinical follow
      up and CT evaluation revealed that 12 patients had partial remission, 4 patients
      had complete remission and 7 patients had no-remission after chemotherapy.
      Statistically, there was no significant correlation between early (30 min),
      delayed (2 hr) T/N ratios and percent retention of Tc-99m MIBI with
      chemotherapeutic response of the lung cancer among the three groups (p > 0.05).
      Results of the current study imply that Tc-99m MIBI uptake and the retention
      index may not correlate with chemotherapy response in lung cancer, so that the
      accuracy of this method needs to be verified in a larger series with additional
      investigation at the molecular level.

PMID- 12043904
TI  - Prognostic values of perfusion-metabolic mismatch in Tl-201 and BMIPP
      scintigraphic imaging in patients with chronic coronary artery disease and left
      ventricular dysfunction undergoing revascularization.
AB  - OBJECTIVES: The aim of this study was to assess the prognostic value of the
      amount of perfusion-metabolic mismatch in revascularized patients with left
      ventricular (LV) dysfunction by means of Thallium (Tl)-201 and BMIPP imaging.
      METHODS: Seventy-six patients with LV dysfunction and coronary artery disease
      underwent Tl-201 and BMIPP imaging. They were revascularized with either coronary
      artery bypass graft or balloon angioplasty and were entered into this study. To
      quantify the amount of perfusion-metabolic mismatch, SPECT images were displayed
      as polar maps and analyzed semiquantitatively. The patients were followed up for
      a mean period of 32 months for cardiac mortality and non-fatal cardiac events.
      Standard follow-up left ventriculography was performed 6 to 12 months after
      revascularization. RESULTS: Thirty-two patients exhibited a large amount of
      perfusion-metabolic mismatch (> 7 segments, group A), 28 patients had a small
      amount of perfusion-metabolic mismatch (2 to 6 segments, group B), and 16
      patients were found to have no perfusion-metabolic mismatch (group C). Similar
      pre-revascularization LVEF of 35 +/- 5%, 34 +/- 8% and 36 +/- 6% increased to 45
      +/- 8% (p < 0.0001), to 38 +/- 8% (p < 0.05), and to 36 +/- 3% (n.s.),
      respectively, after revascularization. The functional improvement after
      revascularization in group A was accompanied by a low rate of cardiac events
      during follow-up and better cardiac event free survival as judged by the Kaplan
      Meier method (p < 0.05, vs. group B and C). CONCLUSION: In revascularized
      patients with severe LV dysfunction, the presence of a large amount of
      perfusionmetabolic mismatch evaluated by Tl-201 and BMIPP imaging identifies
      patients with the best prognosis.

PMID- 12043905
TI  - Salivary function in patients with chronic renal failure undergoing hemodialysis.
AB  - PURPOSE: The aim of this study was to evaluate the changes in salivary gland
      function in patients with chronic renal failure (CRF) undergoing hemodialysis.
      METHODS: The group consisted of 23 patients with CRF (13 female, 10 male; mean
      age: 40 +/- 13 yr) and 14 healthy control subjects (mean age: 40 +/- 13 yr). All
      underwent dynamic salivary gland scintigraphy with gustatory stimulation. After
      intravenous administration of 99mTc pertechnetate, first, perfusion images at 2
      seconds per frame were acquired for 1 minute, then dynamic images at 1 minute per
      frame were acquired for 45 minutes. At 30 minutes after injection, 10 ml lemon
      juice was given for 15 minutes as a gustatory stimulus. We obtained time-activity
      curves derived from regions of interest centered over the four major salivary
      glands. The following functional indices were calculated for each gland: the time
      of maximum radioactivity (Tmax) for the prestimulated period, the time of minimum
      radioactivity (Tmin), as an indicator of velocity of secretion after stimulation,
      and the Lem E5% value as an indicator of the secretion function. RESULTS: When
      the patients with CRF undergoing hemodialysis were compared to the controls,
      there were statistically significant differences in Tmax, Tmin and Lem E5% values
      for bilateral parotid glands, and Tmin values for bilateral submandibular glands
      (p < 0.05), there were no statistically significant differences in Tmax and Lem
      E5% values for bilateral submandibular glands. There were also significant
      differences in Tmax and Lem E5% values for bilateral parotid glands between mild
      oral problems and severe oral problems in patients with CRF (undergoing
      hemodialysis). CONCLUSION: In this study, prolonged Tmax and Tmin values, and
      decreased Lem E5% values for parotid glands and prolonged Tmin values for
      submandibular glands on salivary scintigraphy pointed out decreased
      parenchymatous and excretory function in patients with CRF undergoing
      hemodialysis.

PMID- 12043906
TI  - Identification of sentinel lymph node in breast cancer by lymphoscintigraphy and
      surgical gamma probe with peritumoral injection of scintimammographic agent
      "99mTc MIbI".
AB  - The purpose of this study was to evaluate the efficacy of lymphoscintigraphy and
      the surgical gamma probe (SGP) with peritumoral injection of 99mTc MIBI in
      sentinel lymph node (SLN) detection in breast cancer regardless of whether
      metastatic or not. METHOD: Thirty patients with T1/ T2 breast cancer had
      peritumoral injections of 99mTc MIBI (74 MBq/0.2 ml at 4 different locations) at
      2, 6 and 24 hours before surgery. Anterior, anterolateral, and lateral spot
      images were taken at 10, 30, 45, 60 and 120 minutes. Counts were collected from
      the injection site, affected breast tissue, internal mammaries, axillary and
      supraclavicular regions, and the contralateral side. Peritumoral blue dye was
      also injected at surgery. The first lymph nodes with counts twice the background
      tissue and/or with blue dye uptake were surgically isolated, and
      histopathological evaluations were made. Modified radical mastectomy was
      performed on all patients. RESULTS: 23/30 patients had lymph nodes in scintigrams
      and the sentinel lymph nodes were identified with SGP in 25/30 patients.
      CONCLUSION: Lymphoscintigraphy and subsequent SGP detection with peritumoral
      injection of 99mTc MIBI can be used for identifying SLN in breast cancer.

PMID- 12043907
TI  - A simplified double-injection method to quantify cerebral blood flow and vascular
      reserve using iodine-123 IMP-SPECT.
AB  - We developed and evaluated a simplified double-injection method for iodine-123 N
      isopropyl-p-iodoamphetamine (IMP) to quantify regional cerebral blood flow (rCBF)
      twice in a single SPECT session. The method enabled rapid calculations of rCBF
      with five 10-minute SPECT scans, a fixed distribution volume (Vd), and one-point
      arterial blood sampling to calibrate a standard input function (SIF). METHODS:
      Sixty neurological patients were examined to measure rCBF twice in a single
      session of IMP-SPECT. Patients underwent frequent arterial blood sampling with
      two injections of IMP and acetazolamide challenge. We generated the SIF and
      determined the optimal Vd and calibration time (t(cal)) for the SIF in 30
      patients. Validities of the fixed t(cal) and Vd were assessed in the remaining 30
      patients. Simulation studies were also performed to evaluate the error
      sensitivity of the method. RESULTS: The optimal t(cal) and Vd were 34 min and 30
      ml/ml, respectively. The method was robust in rCBF calculation with noisy SPECT
      data and yielded rCBF with negligible bias and acceptable errors compared with
      those obtained by the double-injection method previously reported. CONCLUSION:
      The method can be applied to measure rCBF twice in a single SPECT session more
      easily and less invasively.

PMID- 12043908
TI  - Hepatic and splenic uptake of Tc-99m HDP in multiple myeloma: additional findings
      on Tc-99m MIBI and Tc-99m sulfur colloid images.
AB  - The authors present a case of multiple myeloma with intense hepatic and splenic
      uptake on Tc-99m HDP bone scan and discuss its clinical implications and possible
      uptake mechanisms. Tc-99m MIBI and Tc-99m sulfur colloid were used to demonstrate
      bone marrow involvement and focal lesions of multiple myeloma.

PMID- 12043909
TI  - Extrarenal uptake of 99mTc-DTPA at the site of bone marrow biopsy.
AB  - Unexpected iliac uptake of 99mTc-DTPA was noted in a 10-year old female referred
      for evaluation of renal function prior to receiving chemotherapy for relapsed
      acute lymphocytic leukemia. This scan finding corresponded to the site of a bone
      marrow biopsy performed five days earlier. X-ray of the area revealed no
      abnormality. It is assumed that the extrarenal uptake was due to increased
      vascularity at the site of recent bone marrow biopsy, most likely due to
      increased osteoblastic reaction in the cortex of the ilium. The patient proceeded
      with the bone marrow transplant and was well at follow-up six months later.

PMID- 12043910
TI  - A case of inferior vena cava thrombosis and pulmonary embolism secondary to acute
      exacerbation of chronic pancreatitis: a rare finding in radionuclide venography.
AB  - A rare case of inferior vena cava (IVC) thrombosis and pulmonary embolism
      secondary to acute exacerbation of chronic pancreatitis was reported.
      Radionuclide venography and lung perfusion scintigraphy were performed on a 46
      year-old male with acute exacerbation of chronic pancreatitis who complained of
      mild swelling of a leg and shortness of breath. Scintigraphy showed an abnormal
      large hot spot at the level of the pancreas and a pulmonary embolism. Enhanced
      abdominal CT revealed an IVC thrombus and a cystic mass adjacent to the IVC.
      Despite the absence of severe abdominal pain, the serum amylase and elastase-1
      levels were very high. These findings indicated that a pancreatic cyst had
      penetrated into the IVC, where it triggered the formation of a thrombus and
      caused a pulmonary embolism. Scintigraphic examination was useful for the
      evaluation of this rare condition.

PMID- 12043911
TI  - "Double imaging" for the diagnostic work-up of alveolar soft part sarcoma with Tc
      99m MIBI.
AB  - The authors report a case of alveolar soft-part sarcoma with lung metastases
      demonstrated by "double imaging" with Tc-99m HDP and Tc-99m MIBI. The tumor
      originated in the soft tissue with direct invasion to the right scapula, which
      was hypoactive on bone scan and hyperactive on Tc-99m MIBI images. A focus of
      dense accumulation of Tc-99m MIBI in the lungs, suggesting metastasis was also
      demonstrated.

PMID- 12043912
TI  - Two phase imaging of 99mTc-SESTAMIBI and 123I-BMIPP for patients with angina
      pectoris.
AB  - We saw three cases of angina pectoris in which 99mTc-SESTAMIBI delayed images at
      rest were useful in diagnosing ischemia risk areas. These findings indicated that
      delayed 99mTc-SESTAMIBI images may be more sensitive to slight ischemia than 123I
      BMIPP images, and suggested that imaging with 99mTc-SESTAMIBI twice at rest may
      be more effective. The addition of 123I-BMIPP SPECT was considered to be useful
      in making an evaluation of the severity of ischemia.

PMID- 12043913
TI  - Recent advances in 99mTc radiopharmaceuticals.
AB  - 99mTc radiopharmaceuticals play an important role in widespread applications of
      nuclear medicine. When 99mTc radiopharmaceuticals first came into use, major
      efforts were directed toward the development of 99mTc radiopharmaceuticals for
      bone imaging and for the excretory functions of the liver and kidneys. In the
      past 20 years, a significant advance has been made in technetium chemistry, which
      provided 99mTc radiopharmaceuticals for assessment of regional cerebral and
      myocardial blood flow. Recent efforts have been directed toward the design of
      99mTc-labeled compounds for estimating receptor or transporter functions. A
      number of bifunctional chelating agents that provide 99mTc labeled proteins and
      peptides of high in vivo stability with high radiochemical yields have also been
      developed. More recently, organometallic technetium and rhenium compounds have
      been introduced as another class of 99mTc radiopharmaceutical design. In this
      manuscript, recent progress in 99mTc radiopharmaceuticals is reviewed with the
      major emphasis laid on key innovations in this field to provide the 99mTc
      radiopharmaceuticals available today.

PMID- 12043914
TI  - The usefulness of serum thyroglobulin levels and Tl-201 scintigraphy in
      differentiating between benign and malignant thyroid follicular lesions.
AB  - OBJECTIVE: To compare the diagnostic capabilities of various serum thyroglobulin
      levels (Tg) and Tl-201 scintigraphy with regard to thyroid follicular lesions.
      METHODS: We examined 80 thyroid follicular lesions (benign: 55, malignant: 25) in
      patients with nodular goiter for whom a pathological diagnosis was made based on
      surgical findings. Tg was measured by an I-125 (radioimmunoassay) method. In Tl
      201 scintigraphy, 74 MBq of Tl-201 chloride was intravenously injected and imaged
      after 10 minutes (early image) and after 120 minutes (delayed image), and the
      scintigrams were evaluated both visually and quantitatively, with special
      attention paid to the part of the nodule with the highest accumulation of Tl-201
      chloride. The cutoff levels of Tg for categorizing the lesions as malignant were
      set at 40, 100, 300, 500, 1,000 and 2,500 microg/l. In Tl-201 scintigraphy,
      method I involved high uptake on both early and delayed images, method 2 involved
      high uptake on only the early image, and method 3 involved high uptake on only
      the early image or the same accumulation in comparison with the normal region on
      the early image, with no washout being quantitatively judged as indicative of
      malignancy. A summary index of overall test performance can be calculated as the
      area under the receiver operating characteristic (ROC) curve (Area (Az)).
      Likelihood ratios for several cutoff levels were also calculated. RESULTS: In the
      diagnosis, Az of Tl-201 (0.95),was larger than that of Tg (0.65). The sensitivity
      and accuracy of Tg at each cutoff level (sensitivity: 4.0% to 76.0%, accuracy:
      50.0% to 72.5%) were lower than with Tl-201 scintigraphy (methods 1-3,
      sensitivity: 76.0-100%, accuracy: 77.5-88.8%). The likelihood ratio for the
      positive results of method 1for Tl-201 scintigraphy, were greatest in the present
      study (13.9), and the likelihood ratio for the negative results of method 3 for
      Tl-201 scintigraphy, (0) was smallest in the present study. CONCLUSION: Diagnosis
      based on Tl-201 washout patterns in which quantitative evaluation is combined
      with visual evaluation appears to be more useful for the differentiation of
      malignant thyroid follicular lesions than diagnosis by Tg.

PMID- 12043915
TI  - What is the diagnosis? Metastasis of right lung from osteosarcoma.

PMID- 12043916
TI  - Magnetic resonance imaging of the shoulder anatomy.
AB  - Magnetic Resonance represents the best method for shoulder study, since it
      enables us to emphasize all the parts making part of this area thanks to high
      anatomical details and a comprehensive view of it. Conventional radiographic
      techniques provide only limited evaluation of soft-tissue anatomy;
      ultrasonography, on the other hand, allows the visualization of tendons, synovial
      spaces and muscle fascicles but it is shown to be unfit above all for osseous
      structure evaluation: TC, finally, is not being employed at present in shoulder
      study.

PMID- 12043917
TI  - Postnatal development of the Syrian golden hamster pancreas--morphological and
      morphometric study.
AB  - Ponderal, morphometric and morphological assessments were used to study the
      Syrian golden hamster pancreas development during the first 70 days of postnatal
      life. The body mass increased 41.74 times in a single growth phase and a mean
      duplication time calculated by linear equation y = 1.76 x - 1.87 (r2 = 0.95), was
      13.4 days. The pancreatic mass increased 44.60 times in two growth phases, the
      first from 2 to 21 days and the second from 28 to 70 days of age. The exponential
      equation obtained by regression analysis for these periods, were: y = 5.21. e
      (0.1810.x) (r2 = 0.95) and y = 156.64. e(0.0094.x (r2 = 0.72), respectively, and
      the calculated duplication times were: 3.8 and 73.7 days, respectively. This
      marked pancreatic growth was due to the increase in all theirs morphological
      compartments, especially of the acini. An inverse relationship was observed in
      the volume density evolution between the acini and the stroma, with a 2.30 times
      increase in the fraction of pancreatic volume occupied by the acini and a 0.26
      times reduction in the connective tissue spaces during studied period. The volume
      density of pancreatic islets increased 4.47 times from 21 to 35 days of age. The
      morphological analysis showed a significant increase in the height and width of
      the acinar cells and in the size of the acini especially from 14 to 21 days of
      age, a relative reduction in the stromal volume, an increase in the size of the
      pancreatic islets and the end of parenchymal cell maturation and lobar and
      lobular organization, so glandular maturity was obtained.

PMID- 12043918
TI  - Surgical anatomy of the variations of the arrangement of the tendons of the
      muscles of the pes anserinus in male adults.
AB  - The descriptions of the morphology of the human pes anserinus (the combined
      insertions of the tendons expansions of medial muscles of the thigh) vary on the
      arrangement of the muscles and tendons that originate the so-called "goose's
      foot". Although descriptions found in the literature include up to 7 muscles,
      most of the authors indicated this anatomical structure as formed only by the
      insertions of the gracilis, sartorius and semitendinosus muscles. Our aim is to
      find out in Brazilian male adult cadavers the most frequent disposition of the
      tendons for application in the orthopedic practice. So far, 60 inferior members
      of 30 cadavers from the laboratories of the Anatomy Departments of the Medical
      Schools of the Universities of Mogi das Cruzes and Santos were studied. The
      dissection was performed in cadavers fixed in 10% formaldehyde solution. The
      specimens were then drawn and photographed. In all 30 cadavers only 3 muscles
      participated in the formation of the pes anserinus but several variations were
      found in the disposition of the tendons. Applications of the anatomical knowledge
      of this tendinous arrangement were discussed.

PMID- 12043919
TI  - Lectin histochemistry of enterocytes sugar residues in the gut of the chick
      embryo and of the newborn.
AB  - The glycoconjugates sugar residues content, distribution and changes in the
      enterocytes of different tracts of the developing intestine of the chick embryo
      and of 1-day-old chick were investigated, using a battery of seven HRP-conjugated
      lectins (DBA, SBA, PNA, WGA, ConA, LTA and UEAI). The results of the present
      research have shown the presence of a large amount of glycoconjugates sugar
      residues in the enterocytes of duodenal, ileal and colonic anlage, starting from
      the beginning of the second week of incubation. Differences were detected among
      the three investigated intestinal segments, as to the time of appearance of the
      glycoconjugates sugar residues in the enterocytes. The duodenal enterocytes
      showed the most precocious appearance of lectin-reactive material, followed by
      the ileal enterocytes and afterwards by colonic enterocytes. The duodenal
      enterocytes were characterised by the presence of SBA binding sites, which were
      not detectable in the duodenal enterocytes of the adult animal.

PMID- 12043920
TI  - Satellite cells and myonuclei in neonatally denervated rat muscle.
AB  - While it is well know that the percentage of stellite cells in relation to
      myonuclei rapidly decreases in aneurally regenerating adult muscle, the fate of
      satellite cells in neonatally denervated muscles has received little attention so
      far. In the present study, rat tibialis anterior muscles were denervated at birth
      and analysed after 5, 7 and 10 weeks. At least 400 myonuclei in each muscle were
      assessed by electron microscopy and the percentage of satellite cell nuclei in
      relation to the number of myonuclei was calculated. The results indicated that
      the percentage of satellite cells steeply declines after neonatal denervation
      and, after 10 weeks, satellite cells were practically lacking in the muscles
      under analysis. This process of exhaustion of the satellite cell pool appears to
      be more rapid in developing than in adult muscles.

PMID- 12043921
TI  - Morphological observations and morphometric analysis in three human fetuses with
      bilateral cervical cystic hygroma.
AB  - Three human fetuses (crown-rump length, CRL, ranging from 71 to 77 mm),
      presenting bilateral cervical cystic hygroma were examined. The specimens were
      cleared and double-stained with alcian blue and alizarin red S for detecting the
      ossification growth patterns in the vertebral column, ribs, ischium, limbs, and
      face. Longitudinal measurements of some long bones in the upper (humerus, ulna,
      radius) and lower (femur, tibia, fibula) limb were taken. The values of both the
      total length (TL) and the ossified part (OL) of each long bone, as well as the
      OL/TL per cent ratio were considered. Reference points were located on the
      mandible, i.e. condylar process (Pcl), coronoid process (Pco), gnathion (GN),
      gonion (GO), inferior interdental point (IDI) for measuring linear dimensions.
      All values obtained were related with those relative to a group of fetuses,
      without any detectable malformation and chromosomal abnormalities, with CRL mean
      value 75 mm, in order to assess the presence of further anomalies, besides the
      cystic hygroma, in the three fetuses considered.

PMID- 12043922
TI  - Engagement in activities revealing the body and psychosocial adjustment in adults
      with a trans-tibial prosthesis.
AB  - The purpose of this study was to examine the effects of the appearance of a
      prosthesis on social behaviour, social discomfort and psychological well-being in
      eleven amputees taking delivery of a prosthesis with a silicone cover. Two new
      scales were developed: the 'Engagement in everyday activities involving revealing
      the body' (EEARB); and the 'Discomfort-Engagement in everyday activities
      involving revealing the body' (Discomfort-EEARB) scales. The psychometric
      properties of these scales were determined using a sample of 101 able-bodied
      adults. The Hospital Anxiety and Depression Scale and the Rosenberg Self-Esteem
      Scale were also used to measure psychological well-being in the amputee sample.
      The EEARB and Discomfort-EEARB proved to have good reliability and validity.
      Comparison of amputees' scores prior to receiving the silicone cosmesis with
      those of the able-bodied adults revealed significant behavioural limitations and
      social discomfort, associated with low self-esteem, anxiety and depression. There
      was a significant increase in amputees' scores three months afier taking delivery
      of their prosthesis, indicating that amputees reported engaging in more
      activities which involved revealing their body, and that they would feel more
      comfortable in situations which involved revealing the body. As the amputee
      sample available was small and self-selected, it is not possible to generalise
      these findings to the amputee population as a whole. However, since there is
      little previous research investigating the effects of the appearance of the
      prosthesis, these findings demonstrate the need for further research in this
      area.

PMID- 12043923
TI  - Laboratory and clinical tests of a prototype pressure sensor for clincial
      assessment of prosthetic socket fit.
AB  - Lower limb prosthetic socket fabrication is a highly refined process relying on
      the prosthetist's skill and experience. Despite their best efforts, patients
      often return with complications. Additionally, clinical application of
      technological advances for the quantification of biomechanical factors at the
      socket interface has not changed in practice. Measuring pressure levels at the
      stump/socket interface could provide valuable information in the process of
      prosthetic socket fabrication, fit and modification. This paper presents findings
      on the performance of a prototype capacitance pressure sensor designed for
      prosthetic socket use. Bench tests using compressed air were performed to measure
      accuracy, hysteresis and drift responses in both a flatbed chamber and a custom
      modified pressure vessel. For the contoured testing, the sensors were placed on
      nine sites on a positive trans-tibial stump mould and enveloped with a silicone
      liner. Additionally, a preliminary clinical evaluation was performed with two
      trans-tibial amputee subjects at the nine sites during normal ambulation. Bench
      test results showed that the prototype capacitance sensor performed well in all
      categories, exhibiting a 2.42% (flatbed) and 9.96% (contoured) accuracy error, a
      12.93% (flatbed) and 12.95% (contoured) hysteresis error, and a 4.40% (flatbed)
      and 6.20% (contoured) drift error. The clinical study showed that after three
      hours of continual use, no noticeable sensor drift occurred between pre and post
      test calibration values. The results from this study were encouraging and the
      authors hope to conduct further laboratory and clinical trials to assess the
      influence of shear force and dynamic loading on sensor response.

PMID- 12043924
TI  - The biomechanical effects of the inclusion of a torque absorber on trans-femoral
      amputee gait, a pilot study.
AB  - This paper reports on a pilot study investigating the effects on the gait of two
      transfemoral amputees of to the inclusion of a torque absorber (TA) and its
      location relative to the knee unit. Both subjects carried out gait tests with a
      prosthesis with no TA with, a TA proximal to the knee unit and with a TA distal
      to the knee unit. Three-dimensional gait analysis was carried out to establish
      the kinematic and kinetic gait parameters of both the prosthetic and sound side.
      It was found that the TA did not significantly affect the sagittal kinetic and
      kinematic parameters of the sound or the prosthetic side. However, for one
      subject the axial rotation of the socket relative to the foot was significantly
      greater with the TA. It was concluded that by using the methodology of this pilot
      study, it is possible to investigate the rotations in the transverse plane within
      the prosthetic limb and pelvis. Further, including a TA may reduce the relative
      motion between the stump and the socket and therefore may decrease skin breakdown
      due to diminished shear forces.

PMID- 12043925
TI  - %VO2max as an indicator of prosthetic rehabilitation outcome after dysvascular
      amputation.
AB  - In this study, independent ambulation of at least 100 metres with/without a cane
      was regarded as successful prosthetic rehabilitation. The subjects were
      classified into two groups according to this criterion at the time of discharge.
      The successful group attained this performance, the other group failed to reach
      this level. The successful group included 8 unilateral trans-femoral amputees
      aged 72.2 +/- 2.1 years who underwent amputation at more than 70 years, and
      succeeded in walking with a prosthesis. The group which failed included 9
      unilateral trans-femoral amputees aged 63.2 +/- 2.1 years who underwent
      amputation between the ages of 60-65 years, and had great difficulty in walking
      with a prosthesis. The purpose of this research was to investigate whether or not
      %VO2max as an indicator of physical fitness is useful in predicting prosthetic
      rehabilitation outcome after dysvascular amputation by comparing these two
      groups. Evaluation of physical fitness was conducted before the subjects began
      prosthetic rehabilitation. Information about each subject before fitting with a
      prosthesis was collected retrospectively from clinical charts made during
      admission. The successful group were capable of strenuous exercise, reaching the
      intensity of 50% VO2max or more. In the group which failed only one reached the
      intensity of 50% VO2max. The working capacity of 50% VO2max or greater would
      appear to be a valid initial guideline level of physical fitness at which an
      amputee can expect to succeed in walking with a prosthesis. Apart from physical
      fitness, a lesser number of comorbidity, good ability to stand on the remaining
      leg, and a strong will to walk were found to be important factors contributing to
      successful prosthetic rehabilitation. This study also showed that age alone was
      not an important factor.

PMID- 12043926
TI  - Gait analysis in prosthetics: opinions, ideas and conclusions.
AB  - A review was performed of the literature of the last eleven years (1990-2000)
      with the topic: "clinical use of instrumented gait analysis in patients wearing a
      prosthesis of the lower limb". To this end a literature search was performed in
      Embase, Medline and Recal. Forty-five (45) articles were identified for study
      from which 34 were reviewed. The reviews were divided into five subtopics: 1)
      adaptive strategies in gait (12 studies); 2) the influence of different parts of
      the prosthesis on gait (12 studies); 3) pressure measurements in the socket in
      gait studies (4 studies); 4) the influence of the mass of the prostheses on gait
      (5 studies); 5) energy considerations in gait (2 studies). A considerable part of
      the studies concerned the adaptive strategies of the amputee in walking and
      running and the evaluation of different prosthetic feet. All aspects and outcomes
      were reviewed concerning the clinical relevance.

PMID- 12043927
TI  - The daily force pattern of spinal orthoses in subjects with adolescent idiopathic
      scoliosis.
AB  - The efficacy of orthotic treatment for children with abnormal spinal curvature
      has been hampered by the lack of comprehensive information about wear
      characteristics. A battery-powered microcomputer system was developed to monitor
      loads exerted by orthoses used to treat children with spinal deformities during
      daily living. The system not only records how well the orthosis has been used,
      but also helps to ensure that the orthosis is being worn as prescribed. Data
      acquisition is controlled by a microcontroller and can be programmed to have
      sample intervals ranging from 1 second to 1 hour. Low power control circuitry is
      designed so that the system can be operated by a battery. In a preliminary study,
      16 subjects (3M, 13F) used this system from 1 to 16 days (9.3 +/- 5.0) with the
      prescribed hours between 16 to 23 hours (22.3 +/- 1.3). This study demonstrated
      the feasibility of the approach, and that this device may increase the
      understanding of orthotic mechanics, and may help patients to wear their orthoses
      in a better way.

PMID- 12043928
TI  - Consumer satisfaction in prosthetics and orthotics facilities.
AB  - The aim of this study was to assess consumer/patient satisfaction with the
      services of the prosthetics and orthotics (P&O) facilities in the north of the
      Netherlands, using a modified SERVQUAL questionnaire. In this questionnaire,
      consumer interests and experiences are assessed on a 5-point Likert scale. The
      questionnaire consisted of 30 items covering 5 domains: tangibles, reliability,
      responsiveness, assurance and empathy and the consumers were invited to give an
      overall rating of satisfaction (scale 1-10). Consumers of four P&O facilities
      were asked to participate. In total 496 consumers (aged 0-76) participated; 279
      consumers received orthopaedic shoes and 217 consumers received either prostheses
      or orthoses. An overall satisfaction rating of 8 or higher was given by 75% of
      the consumers (mean 8.0; sd=1.2). Consumers were defined as satisfied with the
      services of the P&O facility if they rated their experiences on a certain item
      equal or better than their rating of its importance. Eighty-five percent (85%) or
      more of the consumers were satisfied with the P&O facility in 24 of the 30 (80%)
      items of the SERVQUAL questionnaire. Of the 6 less unsatisfying items, 3 were
      related to the domain "tangibles", 2 were related to the domain "empathy" and 1
      to the domain "responsiveness". The management of the P&O facility can use this
      information to increase consumer satisfaction by improving quality and service at
      these items. In general, the degree of consumer overall satisfaction was not
      related to age, gender, and type of assistive device or "length of relationship
      of consumer" and P&O facility. Only consumers who received orthopaedic shoes
      rated their overall satisfaction significantly lower (0.3) than consumers who
      received other types of devices. This difference is clinically not relevant.

PMID- 12043929
TI  - Rates and characteristics of lower limb amputations in Taiwan, 1997.
AB  - This study aims to describe the national incidence rate and characteristics of
      lower limb amputations (LLA) in 1997 from an island-wide database of the national
      health insurance programme in Taiwan. Some 117,647 discharge records from a
      sampled database (1 in 20) of the National Health Insurance Research Database
      were analysed. This study included records (n=171) containing LLA procedures. The
      LLA procedure rates were obtained by multiplying the number of identified
      procedures by 20 as the numerator and mid-year total population of Taiwan in 1997
      as the denominator. Each procedure was further analysed according to the
      demographic characteristics of the patients, cause and level of amputation.
      Summarised gender ratios of LLA procedure rates were obtained by Poisson
      regression analysis. The crude LLA procedure rate was 18.1 per 100,000 population
      per year and the crude major LLA procedure rate was 8.8 per 100,000 population
      per year in Taiwan in 1997. The major cause of LLA procedures was peripheral
      vascular disease (72%), and the toe was most frequently amputated (48%). The LLA
      procedure rates, which increased logarithmically with age of patients, were
      significantly higher in men with a summarised male to female rate ratio of 1.65.
      The age-standardised LLA procedure rate in Taiwan was lower than that reported in
      the United States, Finland, the Netherlands, the United Kingdom (Leeds,
      Middlesborough, and Newcastle), but higher than Spain, Italy, and Japan. The
      trend of an increasing proportion of PVD-related LLA procedures will prompt the
      health professionals to develop strategies for LLA prevention.

PMID- 12043930
TI  - A newly developed socket design for a knee disarticulation amputee who is an
      active athlete.
AB  - This case report describes a newly developed socket design for a world class knee
      disarticulation athlete. To meet the demands concerning especially the suspension
      of the prosthesis a new type of socket was developed. The socket is made from
      carbon fibres and polyaramid fibres and is designed with a slit in the socket
      creating a flexible flap. This allows the amputee to both increase and decrease
      the inner circumference of the socket, thereby allowing the amputee to adjust the
      socket to stump variations. According to the amputee the new design offers an
      excellent fit and enables him to concentrate fully on the technical aspects of
      the different disciplines.

PMID- 12043931
TI  - The use of snowboard boot bindings in a hip disarticulation prosthesis.
AB  - This report describes a new technique for fastening a hip disarticulation socket.
      It was developed at the request of the patient who needed to fasten his
      prosthesis using only one hand, because of a left upper limb disability.
      Snowboard boot bindings were secured to the socket of the prosthesis and allowed
      it to be securely fastened and released using his dominant hand only. The design
      of the bindings permitted a high closing force with minimum one-handed effort by
      the user.

PMID- 12043932
TI  - A wireless telemetry system for training users of upper limb prostheses.
AB  - Telemetry from prosthetic systems is useful in aiding the users and clinical team
      in setting up and training and monitoring in the use of a prosthesis. The
      different forms are discussed and a new radio frequency based telemetry system is
      described. This system uses a computer to display the data and a video mixer to
      place the information on the same screen as the image of the user so that their
      actions and control signals can be simultaneously recorded for later study.

PMID- 12043933
TI  - The influence of local capsaicin treatment on small nerve fibre function and
      neurovascular control in symptomatic diabetic neuropathy.
AB  - Topical treatment with capsaicin cream has been shown to be successful in the
      treatment of different symptomatic nerve disorders like diabetic neuropathy.
      Conflicting data exist on the effect of capsaicin on nerve function and
      neurovascular control especially in patients with diabetic neuropathy. The aim of
      this pilot study was to investigate the impact of topical capsaicin application
      on small nerve fibre function and neurovascular control. Capsaicin cream was
      applied to the feet of 13 patients with symptomatic diabetic neuropathy over a
      period of 8 weeks. Before and during the treatment period, we investigated the
      total symptoms score, the vibration, thermal (heat and cold) and pain perception
      thresholds, and the neurovascular responses to heat and acetylcholine stimuli. In
      addition, the serum plasma levels of substance P, a neurotransmitter of
      nociceptor C-fibres, were measured. A significant improvement in total symptoms
      score was observed during topical capsaicin treatment (18.3+/-3.2 vs. 14.3+/-3.3;
      p<0.05). An improvement in the heat perception threshold was also found (12.7+/
      0.4 degrees C vs. 11.4+/-0.7 degrees C: p<0.05), while other sensory nerve fibre
      functions remained unchanged. No significant change in neurovascular control was
      observed, neither after mild thermal injury nor after stimulation with
      acetylcholine. Serum substance P levels increased after initiation of topical
      capsaicin treatment (72.9+/-5.8 pg/ml vs. 81.7+/-5.0 pg/ml; p<0.05), but returned
      to baseline levels during further treatment (77.4+/-8.3 pg/ml: n.s.). In
      conclusion, topical treatment with capsaicin cream over a period of 8 weeks in
      patients with symptomatic diabetic neuropathy is effective without adverse
      effects on nerve fibre function or neurovascular control.

PMID- 12043934
TI  - Diagnostic value of fasting capillary glucose, fructosamine and glycosylated
      haemoglobin in detecting diabetes and other glucose tolerance abnormalities
      compared to oral glucose tolerance test.
AB  - New diagnostic criteria for diabetes mellitus recommend lowering of the fasting
      plasma glucose to 7.0 mmol/l. In contrast to recommendations of the American
      Diabetes Association (ADA), WHO recommends using the oral glucose tolerance test
      (OGTT) in clinical practice. In this study. based on OGTT results and WHO 1998
      criteria, we determined if measuring fasting capillary glycaemia (FCG) along with
      fructosamine and/or glycosylated haemoglobin allows the detection of glucose
      tolerance abnormalities better than FCG alone. OGTT was performed in 538
      patients. Serum fructosamine was determined in 480 of the patients, and
      glycosylated haemoglobin in 234 of the patients. According to WHO 1998 criteria,
      the patients were divided into groups due to glucose tolerance abnormalities.
      Fructosamine correlated stronger with 2-h post-load glucose concentrations than
      with FCG. HbAlc correlated stronger with FCG than with 2-h post-load glucose.
      Combined use of fructosamine and FCG predicted 2-h post-load glucose better than
      combined use of FCG and HbA1c. Receiver operating characteristic curve analyses
      showed that FCG was the best criterion in discriminating diabetes. Combined use
      of FCG and fructosamine slightly improved the ability to discriminate glucose
      tolerance abnormalities from normal glucose tolerance. FCG is the most effective
      predictor of 2-h post-load glucose and the best criterion for discriminating
      diabetes and other glucose tolerance abnormalities from normal glucose tolerance.
      Fructosamine is a potentially useful post-load glycaemia index. OGTT is
      irreplaceable in identification of patients with high post-load glycaemia.

PMID- 12043935
TI  - Time-dependent urinary bladder remodeling in the streptozotocin-induced diabetic
      rat model.
AB  - Urinary bladder dysfunction and remodeling are well-recognized phenomena in
      diabetes but detailed assessments of tissue morphological changes have not been
      conducted. We studied time-dependent morphological changes in bladders from
      diabetic rats (streptozotocin model) and evaluated the usefulness of automated
      digital imaging technology as an unbiased, reproducible, and convenient method
      for the bladder morphometric analysis. Urinary bladders were isolated from
      diabetic (3 days, 2 weeks or 5 weeks after single injection of streptozotocin, 65
      mg/kg) or control rats (0 or 5 weeks) and were processed for histochemical
      evaluations (hematoxylin/eosin and Mason's trichrome staining). Digital image
      analysis was used to quantify equatorial cross-sectional areas of bladder tissue
      and lumen, as well as relative prevalence of the three primary tissue components
      viz. smooth muscle, urothelium, and extracellular matrix. Digital imaging and
      color segmentation provided reliable and unbiased evaluations of the bladder
      tissue sections. Progressive increases in total bladder tissue and lumen area
      were observed in the diabetic animals relative to controls (p<0.05),
      demonstrating classic hypertrophy and dilation. Prevalence of smooth muscle and
      urothelium (% of total tissue) both increased significantly, but collagen content
      decreased. Average bladder wall thickness and urothelium thickness were
      unchanged. Bladder remodeling during experimental diabetes is associated with
      time-dependent chamber dilation and increased tissue mass. Changes in bladder
      wall composition also occurred in a time-dependent manner, most notably increased
      smooth muscle and urothelium and decreased collagen prevalence. Furthermore,
      automated digital imaging technologies provide an unbiased, reproducible, and
      convenient method for detailed morphometric analysis of bladder tissues.

PMID- 12043936
TI  - Polymorphonuclear leukocyte membrane fluidity, at baseline and after in vitro
      activation, in obesity with or without diabetes mellitus.
AB  - We studied a group of 28 obese subjects (mean age 38.2+/-13.5 years, body mass
      index 35.0+/-5.6 kg/m2) with insulin resistance demonstrated employing an
      euglycemic hyperinsulinemic clamp, subdivided into a subgroup with normal glucose
      tolerance (NGT) and a subgroup with type 2 diabetes mellitus (DM). We examined
      the polymorphonuclear leukocyte (PMN) membrane fluidity at baseline and after
      activation with 4-phorbol 12-myristate 13-acetate (PMA) or N-formyl-methionyl
      leucylphenylalanine (fMLP). At baseline, PMN membrane fluidity was significantly
      decreased in both subgroups compared to normals. In obese subjects with NGT no
      correlation was found between this PMN determinant and the parameters reflecting
      the insulin-resistance degree (glucose disposal [M] and metabolic clearance rate
      of glucose [MCR]), while in type 2 DM subjects the PMN membrane fluidity was
      correlated to M and MCR. After activation with PMA and fMLP, no variation in PMN
      membrane fluidity was observed in normals, while in obese subjects with NGT an
      early decrease was present only after fMLP activation, and in obese subjects with
      type 2 DM there was a constant and significant decrease of this PMN parameter
      after activation with PMA and fMLP. Our interest in the study of the PMN membrane
      fluidity emerges from its known role in PMN function, especially considering that
      PMN cells, together with monocytes, may be mediators of vascular damage.

PMID- 12043937
TI  - Glycohaemoglobin measurement: methodological differences in relation to
      interference by urea.
AB  - The aim of this study was to investigate the agreement between a cation-exchange
      HPLC method and a boronate affinity method of measuring glycohaemoglobin (HbA1c),
      with particular reference to the effect of elevated urea concentration. HbA1c was
      measured by both methods in samples from 75 subjects who were classified as
      diabetic with normal (n=36) or abnormal (n=12) renal function, and non-diabetic
      with normal (n=8) or abnormal (n=19) renal function. Urea was found to cause a
      clinically significant interference in the HPLC method at a level > or =17.0
      mmol/l. Each increase of 1 mmol/l urea in serum was associated with an absolute
      increase of 0.04% in the HbA1c value as measured by the HPLC method. The boronate
      affinity method for HbA1c did not appear to be affected by elevated urea
      concentration. There was significant correlation (r=0.97, p<0.001) between HbA1c
      results obtained by the two methods, however, results obtained by the boronate
      affinity method were generally lower. The discrepancy between results obtained by
      the two methods was particularly marked in uraemic samples from diabetic
      subjects, as the HPLC/boronate affinity difference increased as the HbA1c
      increased and also as the urea concentration increased. Results indicate that
      blood from diabetic patients with renal failure may give erroneously high HbA1c
      values by HPLC. Results also highlight the importance of choosing appropriate
      clinical samples and statistical techniques when evaluating or comparing test
      methods.

PMID- 12043938
TI  - Anion-selective amplification of glucose-induced insulin secretion.
AB  - The functional roles of anions on glucose-induced insulin secretion are poorly
      understood. We investigated the effects of the monovalent anions thiocyanate,
      iodide, bromide, nitrate and chloride on the dynamics of insulin secretion in
      isolated pancreatic islets from non-inbred Umea ob/ob mice. All anion species (12
      mM), except Cl-, significantly amplified glucose-induced (20 mM) first- and
      second-phase insulin secretion (selectivity sequence: SCN->NO3->I->Br->Cl-).
      Simultaneously, the anions reduced the lag-time prior to the initiation of the
      secretion (SCN-=I-=NO3->Br->Cl-). The results indicate that pancreatic beta-cell
      activation can be initiated and amplified by an anion-selective mechanism showing
      increasing degrees of activation in the order of the anion series of Hofmeister.
      On the basis of the strikingly similar anion selectivity of amplified secretion
      and shortened lag-phase, we suggest that both types of anion effects are caused
      by action at a single site on the beta-cell.

PMID- 12043939
TI  - Western Negev Mobile Diabetes Care Program: a model for interdisciplinary
      diabetes care in a semi-rural setting.
AB  - We describe a mobile diabetes clinic aimed to provide comprehensive,
      interdisciplinary care to patients with diabetes resident on a semi-rural area. A
      mobile, tertiary care diabetes clinic, composed of a diabetologist, a diabetes
      nurse-educator and a dietitian, was created. The clinic regularly visited the
      primary-care facilities of 3 towns of the Western Negev, a semi-rural area of
      southern Israel. A standardized, computer-based clinical protocol was applied.
      Analysis of data was performed on records of all patients who had had at least 2
      visits to the clinic. Of 492 patients who met the inclusion criteria, 93.6% were
      diagnosed with type 2 diabetes, 58% were female, the mean age was 60 years and
      the mean time after diagnosis of diabetes was 10 years. Most patients had not
      visited a diabetes center before implementation of the mobile clinic. Parameters
      of clinical practice such as nutritional advice by a dietitian, interaction with
      a diabetes nurse-educator, performance of periodic ophthalmologic examination,
      and measurement of microalbumin excretion improved dramatically after opening of
      the mobile clinic. Modifiable clinical variables such as body mass index
      (p<0.0001), systolic (p<0.001) and diastolic (p<0.05) blood pressures, fasting
      plasma glucose (p<0.001), hemoglobin A1c (p<0.01), LDL-cholesterol (p<0.01) and
      HDL-cholesterol (p<0.0001) improved significantly after implementation of the
      program. The implementation of a mobile diabetes care program in an area of low
      density population is feasible. Significant improvement in parameters of clinical
      practice and of modifiable variables of diabetes control was achieved. The mobile
      diabetes clinic brought the interdisciplinary diabetes-care team to the patients'
      area of residence. Limited manpower answered the requirement of a geographically
      spread population.

PMID- 12043940
TI  - Undiagnosed diabetes and impaired glucose regulation in adult Ghanaians using the
      ADA and WHO diagnostic criteria.
AB  - Fasting glucose and oral glucose tolerance test (OGTT) criteria for glucose
      homeostasis were compared in a cross-sectional cluster, community study in Accra,
      Ghana. A total of 4636 subjects without prior diagnosis of diabetes had fasting
      plasma glucose, 2-hour OGTT and measurement of cardiovascular risk factors. Mean
      age of subjects was 44.2 years: 39.1% of subjects were males. The overall
      prevalence of undiagnosed diabetes ascertained with both criteria was 4.5%
      (n=209). The prevalence of undiagnosed diabetes by fasting (3.2%) and OGTT (3.1%)
      criteria were similar (p>0.05). The prevalence of impaired glucose tolerance
      (IGT) (15.8%) was higher than that of impaired fasting glucose (IFG) (10.7%).
      Only 56.5% (n=83) of subjects with diabetes by fasting criteria also had diabetes
      by OGTT criteria. Sixty-two subjects (42.8%) with diabetes by OGTT had normal or
      impaired fasting glucose. There was poor agreement between the two diagnostic
      criteria (kappa=0.31). The concordant normoglycaemic group was the youngest and
      had the lowest body-mass index (BMI), waist girth, waist-hip ratio (WHR), total
      cholesterol, and systolic and diastolic blood pressures. The concordant diabetic
      group, in contrast, had the highest BMI, waist girth, WHR, total cholesterol and
      triglyceride levels. Both systems gave similar undiagnosed diabetes rates but
      dissimilar IFG and IGT rates. There was poor agreement between the two diagnostic
      criteria. Diagnostic criteria influenced cardiovascular risk factors. A case may
      be made for using both criteria in order to ascertain all "diabetes" and all "at
      risk" subjects.

PMID- 12043941
TI  - Concise synthesis and enzymatic resolution of L-(+)-homophenylalanine
      hydrochloride.
AB  - The N-acetyl-homophenylalanine ethyl ester was synthesized by a simple three-step
      reaction strategy. L-(+)-homophenylalanine hydrochloride with 98% ee was obtained
      through a kinetic resolution process using industrial enzyme alcalase. Compared
      with other methods, this strategy has the advantage of economical and simple
      procedure giving high product optical purity.

PMID- 12043942
TI  - Quantitative analysis of incomplete HPLC resolution of enantiomers. Fit of
      polarimetric detection for D- and L-phenylalanine to a gaussian function.
AB  - This report compares laser-based polarimetric and UV data for quantitating
      incompletely resolved enantiomers by HPLC. Using L- and D-phenylalanine as a
      working model, response data is shown across the entire detection region while
      emphasizing the regions at or near 100% L, 100% D and 50:50 L:D at resolutions
      between 0.4 and 1.4. In general, the poorer the resolution, the greater the
      improvement in detectability with the polarimeter when compared to UV detection.
      This is due to the inherent bipolar nature of the polarimetric signal, which
      creates a well-defined crossing point for integration of an enantiomeric pair. In
      our previous work, we described the improvement in measurement precision when
      applying a bipolar gaussian peak model to the raw chromatographic peak data. This
      study will measure the model's effect on improving accuracy. This study should be
      applicable to other chiroptical detection strategies that produce a bipolar
      signal for enantiomers, such as circular dichroism and circularly polarized
      luminescence.

PMID- 12043943
TI  - Absolute stereochemistry of chiral C60 fullerene bis-adducts.
AB  - To determine the absolute configuration of chiral fullerene bis-adducts, we have
      studied the double Bingel reaction of C60 with chiral tether (2S,3S)-(-)-9
      derived from (R,R)-(+)-tartaric acid, and have succeeded in isolating two
      possible chiral bis-adducts 10a (5%) and 10b (2%) in addition to the Cs
      symmetrically added derivative 10c (40%). The CD spectra of chiral bis-adducts
      [CD(+)281]-10a and [CD(-)281]-10b show very intense Cotton effects, which are
      almost of mirror image, indicating that their chiral C60 pi-electron systems are
      enantiomeric each other. The 1H and 13C NMR spectra of 10a and 10b indicate that
      they have C2-symmetrical structures, and the vicinal coupling constants between
      two equivalent protons H-2 and H-2' were determined as 1.2 Hz for 10a and 1.8 Hz
      for 10b, respectively by the 13C satellite band method. From the conformational
      analyses, the absolute configurations of these chiral C60 fullerene bis-adducts
      were unambiguously determined as [CD(+)281]-(S,S,fC)-10a and [CD(-)281]-(S,S,fA)
      10b, respectively.

PMID- 12043944
TI  - Optical resolution of 5-alkyl-delta-valerolactones and synthesis of optically
      active 5-fluoroalkanols.
AB  - Optical resolutions of 5-alkyl-delta-valerolactones were carried out by
      derivatization to the diastereomeric amides, in which (R)-(+)-1-(1
      naphthyl)ethylamine or (S)-(-)-1-phenylethylamine were used as resolving agents.
      Optically active 5-fluoroalkanols, useful intermediates for fluorinated
      ferroelectric liquid crystals, were derived from the resolved lactones in four
      steps without racemization.

PMID- 12043945
TI  - Real-time assessment of enantiomeric purity via a polarimetric/absorption
      detector response function.
AB  - The development of methodology appropriate for the rapid and precise assessment
      of enantiomeric purity is a critical need in the life sciences with impact in a
      number of areas including biomedical research, biotechnology, and pharmaceutical
      science. Real-time assessment of enantiomeric purity is critical to decisions
      related to possible product purity and/or the need for, and the type of
      additional processing. Recently, we have shown that laser-based polarimetric
      detection, in combination with ultraviolet detection, can be used to assess
      enantiomeric purity in real-time as an adjunct to the separation process. A mass
      independent response function is obtained from the ratio of the normalized
      polarimetric signal relative to the normalized UV signal. This response ratio
      will be shown to be equivalent to the enantiomeric excess and independent of
      concentration and chromatographic resolution. The methodology will be evaluated
      as a function of injected mass, enantiomeric excess, chromatographic resolution,
      and peak asymmetry.

PMID- 12043946
TI  - Enantiopure spiro[3.3]heptane-2,6-dicarboxylic acid.
AB  - Using chiral HPLC and 13C NMR analyses, the optical purity of (+)
      spiro[3.3]heptane-2,6-dicarboxylic acid (1) obtained by the known diastereomer
      method with brucine was first clarified to be 90% e.e., which was conventionally
      considered to be 100% e.e. Among the ester derivatives synthesized, dicinnamyl
      spiro[3.3]heptane-2,6-dicarboxylate (2) was found to show high optical separation
      ability on the chiral HPLC with cellulose phenyl carbamate stationary phase
      eluting with hexane/2-propanol (10/1, v/v) at a flow rate of 0.4 ml/min at 35
      degrees C (separation factor, a, 1.14), and the isolated optically pure (+)- and
      (-)-2 show [alpha]D26 of + 1.84 degrees (c = 1.74, CHCl3) and -1.84 degrees (c =
      1.74, CHCl3), respectively. Acidic hydrolysis of optically pure (+)-/(-)-2
      without racemization yielded optically pure (+)-/(-)-1, exhibiting [phi]405(270 =
      + 21.1 degrees ([phi]D27 = +9.1 degrees) (c = 5.33, acetone) and [phi]405(27) = 
      21.1 degrees ([phi]D27 -9.1 degrees) (c = 5.32, acetone), respectively.

PMID- 12043947
TI  - Clinical pharmacology of antimicrobial use in humans and animals.
AB  - Veterinary public health is a frontier in the fight against human disease,
      charged to control and eradicate zoonotic diseases that are naturally transmitted
      between vertebrate animals and man. Currently there is a need for clinical
      pharmacologists and all health care givers to limit the development of bacterial
      resistance in humans to contain the increased health care expenditures related to
      morbidity and mortality associated with the use of antimicrobials. The
      development of resistance predates the use of antibiotics and will always be a
      problem to the successful treatment of patients. Ongoing discussion debates the
      extent to which antibiotic use in animals contributes to the development of
      antibiotic resistance in humans. The veterinary use ofantibiotics as
      antimicrobial growth promoters is thought to influence the prevalence of
      resistance in animal bacteria and to be a risk factor for the emergence of
      antibiotic resistance in human pathogens. Transfer of antibiotic resistant
      bacteria from animals to humans may occur via contact, including occupational
      exposure and via the food chain. Resistance genes may transferfrom bacteria of
      animals to human pathogens in the intestinal flora of humans. Prevention of the
      development of resistance in humans necessitates good animal husbandry and
      hygienic measures to prevent cross contamination and a decrease in the use of
      antibiotics. Appropriate use of antibiotics for food animals will preserve the
      long-term efficacy of existing antibiotics, support animal health and welfare,
      and limit the risk of transfer of antibiotic resistance to humans. Investigators
      must also develop new antimicrobial agents. Poole (J Pharmacy Pharmacol
      2001;53:283) recommends targeting the three predominate mechanisms of development
      of resistance by antimicrobials (i.e., antibiotic inactivation, target site
      modification, and altered uptake via restricted entry and/or enhanced efflux) to
      specifically complement the development of novel agents with novel bacterial
      targets. Bacterial resistance and its selection may be evaluated by comparing the
      relationship to antibiotic pharmacokinetic (PK) values obtained from serum
      concentrations and organism MICs (minimum inhibitory concentrations;
      concentration-dependent killing) to reveal culture and sensitivity tests in
      patients. Pharmacodynamic (PD) models may be developed to identify factors
      associated with the probability that bacterial resistance will develop. Thomas et
      al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of
      PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology
      is to work with PK/PD models such as these to determine the best use of
      antibiotics in humans to minimize the development of resistance. The role of any
      regulatory body responsible for the protection of the public health and food
      safety for consumers is to assess risk and to then communicate and manage the
      risk. Scientific uncertainty must be interpreted to propose sound policy options.
      The conversion of sound science into an appropriate regulatory policy to protect
      the public health is most important.

PMID- 12043948
TI  - HIV testing in early clinical trials: who should decide whether it is warranted?
AB  - In phase I clinical trials intended for healthy volunteers, testing for human
      immunodeficiency virus (HIV) is often times part of a routine screening procedure
      to determine eligibility. The rationale is to safeguard volunteers, to protect
      the scientific integrity of a clinical trial, and/or to facilitate the process of
      drug development. Asymptomatic HIV-positive individuals are at increased risk for
      adverse events, and participating in a phase I clinical trial could also
      interfere with effective treatment for their disease. Although the Food and Drug
      Administration has not established a policy regarding HIV testing in clinical
      trials, some institutional review boards (IRBs) impose restrictions. The role of
      an IRB is to protect the rights and welfare of human subjects in clinical trials.
      Restricting testing does not protect subjects and may in fact harm them;
      therefore, an IRB should not restrict testing proposed by a pharmaceutical
      sponsor in agreement with a clinical investigator.

PMID- 12043949
TI  - Hawthorn.
AB  - A review with 54 references covers all aspects of hawthorn, the genus Crataegus,
      including its traditional uses, chemical constituents, pharmacological
      activities, and clinical effects. Although the effectiveness of hawthorn on the
      treatment of cardiovascular diseases has received extensive attention worldwide,
      further scientific research on various areas such as pharmacokinetics, mechanism
      of actions will be necessary to ensure its safe and effective usage.

PMID- 12043950
TI  - Acetylator phenotype and genotype in HIV-infected patients with and without
      sulfonamide hypersensitivity.
AB  - Adverse reactions to sulfonamides occur at a higher frequency in patients
      infected with the human immunodeficiency virus (HIV) than noninfected patients.
      Some studies have suggested that patients with the slow acetylator phenotype are
      predisposed to these reactions, whereas other studies suggest that the slow
      acetylator genotype is not a predisposing factor. To rationalize these seemingly
      contradictory observations, the authors determined the N-acetyltransferase 2
      (NAT2) genotype and phenotype in patients with and without a history of
      hypersensitivity reactions to sulfonamides. HIV-infected patients with a history
      of a delayed-type hypersensitivity reaction to trimethoprim-sulfamethoxazole were
      enrolled, along with a group of AIDS patients with no history of hypersensitivity
      (delayed or immediate). NAT2 phenotype was determined in both groups using
      dapsone, while the genotype was determined using a polymerase chain reaction
      restriction fragment length polymorphism assay. Ten of 14 patients (71%) with a
      history of hypersensitivity exhibited the slow acetylator phenotype, while 8 of
      14 patients (57%) without such a history exhibited this same phenotype (odds
      ratio [OR] = 1.9, 95% confidence interval [CI] = 0.4-9.0; p = 0.69, Fisher's
      Exact Test). While 9 of 14 patients (64%) with a history of hypersensitivity
      exhibited a slow acetylator genotype, only 4 of 14 patients (29%) without such a
      history exhibited this genotype (ns). There were more instances of discordance
      between deduced and actual phenotype in the nonhypersensitive patients (n = 4)
      than in the hypersensitive patients (n = 1). The reported higher frequency of the
      slow acetylator phenotype among patients with a history of hypersensitivity to
      sulfonamides does not appear to be explained by metabolic changes that would
      cause discordance between acetylator genotype and phenotype.

PMID- 12043951
TI  - A mechanistic approach to understanding the factors affecting drug absorption: a
      review of fundamentals.
AB  - This article provides an overview of the patient-specific and drug-specific
      variables that can affect drug absorption following oral product administration.
      The oral absorption of any chemical entity reflects a complex spectrum of events.
      Factors influencing product bioavailability include drug solubility,
      permeability, and the rate of in vivo dissolution. In this regard, the
      Biopharmaceutics Classification System has proven to be an important tool for
      predicting compounds likely to be associated with bioavailability problems. It
      also helps in identifying those factors that may alter the rate and extent of
      drug absorption. Product bioavailability can also be markedly influenced by
      patient attributes such as the integrity of the gastrointestinal tract,
      physiological status, site of drug absorption, membrane transporters, presystemic
      drug metabolism (intrinsic variables), and extrinsic variables such as the effect
      of food or concomitant medication. Through an awareness of a drug's
      physicochemical properties and the physiological processes affecting drug
      absorption, the skilled pharmaceutical scientist can develop formulations that
      will maximize product availability. By appreciating the potential impact of
      patient physiological status, phenotype, age, gender, and lifestyle, dosing
      regimens can be tailored to better meet the needs of the individual patient.

PMID- 12043952
TI  - Pharmacokinetics of cefoperazone and sulbactam in liver transplant patients.
AB  - The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9
      liver transplant patients. Cefoperazone and sulbactam were administered as an
      intravenous infusion over 30 minutes every 12 hours for six doses, and multiple
      blood samples were collected immediately after the first dose (administered
      during the surgery) and after the last dose. The concentrations of cefoperazone
      and sulbactam in serum and, when possible, in urine and bile collected over one
      dosing interval were measured by high-pressure liquid chromatography. The
      concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam
      ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative
      clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than
      the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of
      cefaperazone, although not statistically significantly different, was prolonged
      in all patients during the postoperative period. The clearance of sulbactam
      (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal
      renal function but was comparable to what has been reported in patients with
      renal impairment and in critically ill patients. There were no significant
      differences in any of the pharmacokinetic parameters of sulbactam during and
      after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were
      significantly altered in liver transplant patients compared to what has been
      reported in normal subjects but were similar to what has been reported in
      patients with liver and renal impairment. There was a significant impairment in
      the biliary excretion of cefoperazone during the postoperative period in liver
      transplant patients. Although the percentage of the dose of cefoperazone excreted
      in the bile was drastically reduced, the biliary concentrations were generally
      high and above the MIC for most organisms. Given that both renal and hepatic
      elimination of cefoperazone is decreased, leading to a lower clearance and longer
      half-life in liver transplant patients, lower doses (1-2 g per day) of
      cefoperazone may be sufficient in liver transplant patients during the immediate
      postoperative period.

PMID- 12043953
TI  - Pharmacokinetics and pharmacodynamics of extended-release glipizide GITS compared
      with immediate-release glipizide in patients with type II diabetes mellitus.
AB  - This study was designed to compare the pharmacokinetic and short-term
      pharmacodynamic profile of extended-release glipizide GITS (Glucotrol XL) given
      in a dosage of 20 mg once daily with that of immediate-release glipizide
      (Glucotrol) 10mg twice daily in patients with type II diabetes mellitus. In an
      open-label, randomized, two-way crossover study, each glipizide formulation was
      administered for 5 days. Serial blood samples were drawn at baseline and on the
      5th day of each treatment phase for measurement of glipizide, glucose, insulin,
      and C-peptide concentrations. At steady state, the mean Cmax after immediate
      release glipizide was significantly greater than after glipizide GITS, and the
      tmax was considerably shorter. Although the mean Cmin with glipizide GITS was
      about 80% higher than with immediate-release glipizide, the mean AUC0-24 was
      significantly lower. Despite the lower plasma concentrations with glipizide GITS
      in this short-term study, the two formulations had similar effects on serum
      concentrations of glucose, insulin, and C-peptide. The absence of a pronounced
      peak plasma concentration with the GITS formulation might confer advantages in
      terms of maintaining clinical effectiveness and reducing the potential to cause
      adverse effects.

PMID- 12043954
TI  - Effect of food on the pharmacokinetics of (-) and (+) dOTC when administered as
      an oral racemate.
AB  - The objective of this study was to evaluate the effect of food on the
      pharmacokinetics of racemic dOTC, a nucleoside analogue reverse transcriptase
      inhibitor, in adult male volunteers. Twelve healthy adult male subjects were
      enrolled in a randomized, open-label, single-dose crossover study. All were
      nonsmoking, within 15% of ideal body weight, and between 18 and 50 years of age.
      Subjects received single oral doses of 800mg racemic dOTC, in random order,
      either fed or fasted. The meal given to fed subjects was the standard Food and
      Drug Administration high-fat breakfast, and all subjects completed both study
      periods. Sixteen plasma samples for pharmacokinetic assessments were collected
      for 72 hours following dosing and assayed for (-) and (+) dOTC concentrations.
      Area under the plasma concentration-time curve (AUC), maximum observed plasma
      concentration (Cmax), and time to maximum concentration (tm) were determined for
      each enantiomer by standard noncompartmental techniques. Statistical hypothesis
      testing was by Wilcoxon signed rank, and the two one-sided tests procedure was
      used to determine bioequivalence between thefed and fasted study periods. The
      only effect of coadministration of racemic dOTC with food was a delay in time to
      peak concentration (t(max) of between 0.6 and 0.7 hours for both (-) and (+) dOTC
      stereoisomers (p < or =0.02). Neither AUC (p > or = 0.10) nor Cmax (p > or =
      0.35) differed significantly between the fed and fasted study periods for either
      (-) or (+) dOTC. Both AUC and Cmax were equivalent between the fed and fasted
      study periods. It was concluded that there is no clinically significant effect of
      a high-fat meal on the pharmacokinetics of either (-) or (+) dOTC when
      administered orally as a racemic mixture.

PMID- 12043955
TI  - A new solution-based intranasal triamcinolone acetonide formulation in patients
      with perennial allergic rhinitis: how does the pharmacokinetic/pharmacodynamic
      profile for cortisol suppression compare with an aqueous suspension-based
      formulation?
AB  - The present study was undertaken to describe the pharmacokinetics of a new
      solution-based intranasal triamcinolone acetonideformulation (Tri-Nasal) in
      patients with perennial allergic rhinitis and to use a
      pharmacokinetic/pharmacodynamic (PK/PD) simulation approach to compare the
      potential effects on plasma cortisol with that of an aqueous suspension-based
      nasal triamcinolone acetonide formulation (Nasacort AQ). Data from an open-label,
      randomized, three-way crossover study in patients with perennial allergic
      rhinitis receiving three doses (100, 200, and 400 microg) of a nasal solution
      based triamcinolone acetonide formulation (Tri-Nasal) over 7 days were used to
      describe the pharmacokinetics of this formulation. Available literature data for
      a suspension-based aqueous triamcinolone acetonide formulation (Nasacort AQ) were
      used to describe its pharmacokinetic profile after similar single doses of 110,
      220, and 440 microg. A PK/PD simulation approach was used to predict the
      anticipated cumulative cortisol suppression (CCS) of these two formulations.
      These simulations suggested a cortisol suppression of 8% to 16% for the single
      and steady-state doses of the solution-based product. Similar CCS estimates were
      predicted for equivalent doses of the aqueous suspension-based triamcinolone
      acetonide formulation with no difference between both formulations. Post hoc
      power analysis suggested that the predicted cortisol suppression is not likely to
      be significant for either preparation, including the clinically recommended doses
      of 200 and 220 microg of the solution-based and suspension-based formulations,
      respectively. In summary, based on the results of this PK/PD simulation, the
      plasma levels observed afternasal administration of the solution or the aqueous
      suspension are unlikely to induce a clinically relevant cortisol suppression,
      especially for the recommended dosing regimens of 200 and 220 microg/day.

PMID- 12043956
TI  - Lack of effect of sucralfate on the absorption and pharmacokinetics of
      rosiglitazone.
AB  - The aim of the present study was to investigate the effect of sucralfate
      pretreatment on the pharmacokinetics of rosiglitazone following a single oral
      dose in healthy male volunteers. After an over night fast, and according to a
      randomized schedule, each volunteer (n = 9) received a single oral dose of
      rosiglitazone 8 mg (Avandia tablets, 4 mg x 2) with or without pretreatment of
      sucralfate 2 g (Recolfate tablets, 1 g x 2) in an open-label crossover study with
      a 2-week washout period. Plasma samples were collected over a period of 24 hours
      at regular intervals. Safety assessment included monitoring of the vital signs,
      blood parameters, and ECG. No statistically significant differences (p > 0.05)
      were observed for any of the calculated rosiglitazone pharmacokinetic parameters
      in the two treatment groups. The mean parameters, AUC0-infinity and Cmax,
      following rosiglitazone administration alone were 3825.02 ng x h/ml and 664.47
      ng/ml, respectively, and for rosiglitazone administered after pretreatment with
      sucralfate were 4848.19 ng x h/ml and 624.88 ng/ml, respectively. The t(max) for
      rosiglitazone alone and for rosiglitazone after sucralfate treatments was 1.11
      and 1.67 hours, respectively. The mean elimination half-life for rosiglitazone
      and rosiglitazone after sucralfate treatment was 4.35 and 4.51 hours,
      respectively. Fraction of rosiglitazone absorbed was calculated by the Wagner
      Nelson method, and no statistically significant difference (p > 0.05) was
      observed for the two treatments. Since sucralfate pretreatment did not show any
      significant difference in the pharmacokinetics of rosiglitazone, no dose
      adjustment is warranted for rosiglitazone when it is administered with
      sucralfate.

PMID- 12043957
TI  - Progressive cholestatic liver disease associated with clarithromycin treatment.
AB  - The authors report a case of an acute toxic cholestatic reaction to
      clarithromycin, proven by liver biopsy, in a patient with comorbid diseases,
      prior exposure to erythromycin and ultimate death. No autopsy was performed. A 59
      year-old woman with diabetes mellitus and chronic renal insufficiency received
      clarithromycin 500 mg twice daily for 3 days for acute maxillary sinusitis and
      then developed a rash and jaundice. She was hospitalized 11 days after stopping
      clarithromycin. Progressive cholestatic jaundice accompanied by oligo-anuric
      renal failure requiring hemodialysis ensued. Liver biopsy showed pure
      bilirubinostasis without parenchymal inflammation. On the 22nd hospital day,
      after clinical deterioration, she died from an apparent cardiopulmonary death.
      This is the first report in the literature of a fatality associated with a short
      term, low (1 g) daily dose of drug-induced pure cholestasis, an entity not
      previously identified with severe drug-induced hepatotoxicity.

PMID- 12043958
TI  - Phylogenetic analyses of small subunit ribosomal RNA coding regions reveal a
      monophyletic lineage of euglyphid testate amoebae (Order Euglyphida).
AB  - The Testaceafilosia includes amoebae with filopodia and with a proteinaceous,
      agglutinated or siliceous test. To explore the deeper phylogeny of this group, we
      sequenced the small subunit ribosomal RNA coding region of 13 species, including
      the first sequence of an amoeba with an agglutinated test, Pseudodifflugia sp.
      Phylogenetic analyses using maximum parsimony and maximum likelihood methods as
      well as neighbor joining method yielded the following results: the order
      Euglyphida forms a monophyletic lineage with the sarcomonads as sister group. The
      next related taxa are the Chlorarachnea and the unidentified filose strain N-Por.
      In agreement with the previous studies the Phytomyxea branch off at the base of
      this lineage. The Monadofilosa (Testaceafilosia and Sarcomonadea) appear
      monophyletic. The Testaceafilosia are polyphyletic, because Pseudodifflugia sp.
      is positioned as the sister taxon to the sarcomonads. Within the order Euglyphida
      Paulinella branches off first, together with Cyphoderia followed by
      Tracheleuglypha. In maximum likelihood and neighbor joining analyses, the genus
      Euglypha is monophyletic. The branching pattern within the order Euglyphida
      reflects the evolution of shell morphology from simple to complex built test.

PMID- 12043959
TI  - Involvement of actin dephosphorylation in germination of Physarum sclerotium.
AB  - The plasmodium of Physarum polycephalum grows without cytokinesis and shows an
      active cytoplasmic streaming under wet and nutritious conditions. It can undergo
      reversible differentiation into several types of dormancy to survive in adverse
      environments. Temperature change or osmotic stress leads to cytoplasmic division
      of the plasmodium into cells containing one or more nuclei: these form a
      macrocyst, the spherule. Desiccation also induces cell division of the plasmodium
      followed by formation of a sclerotium, a dormant body resistant to dry stress.
      More than half of the actin in a sclerotium is phosphorylated at a single site,
      threonine 203, resulting in loss of its ability to polymerize into actin
      filaments. In the present study, actin phosphorylation was found in the
      sclerotium but not in either the plasmodium or in the spherule. This result
      suggests that phosphorylation of sclerotium actin may be related to the mechanism
      associated with desiccation resistance rather than morphological changes through
      cell compartmentalization in the macrocyst formation. Moreover. dephosphorylation
      of the phosphorylated form of sclerotium actin began within 5 min after addition
      of water. Dephosphorylation was not affected by sucrose and sorbitol sugars, but
      was inhibited by ammonium bicarbonate, ammonium phosphate, sodium phosphate,
      NaCl, and KCl in a dose-dependent manner. On the other hand, in germination of
      the sclerotium there was measurable sensitivity to both carbohydrates and salts.
      Actin dephosphorylation seems to be one of the important processes in the early
      phase of sclerotium germination.

PMID- 12043960
TI  - Giardia intestinalis glucosamine 6-phosphate isomerase: the key enzyme to
      encystment appears to be controlled by ubiquitin attachment.
AB  - The cyst wall of the parasitic protozoan, Giardia intestinalis, is composed of a
      polymer of N-acetylgalactosamine, the precursor of which is synthesized by an
      inducible enzyme pathway. The first enzyme in this pathway, glucosamine 6
      phosphate isomerase, is transcriptionally regulated. During encystment and in
      mature cysts this isomerase appears to be modified by ubiquitin attachment. Thus,
      it might be targeted for destruction by an ubiquitin-mediated pathway, suggesting
      that glucosamine 6-phosphate isomerase expression is tightly regulated.

PMID- 12043961
TI  - Spironucleus vortens (Diplomonadida) in the Ide, Leuciscus idus (L.)
      (Cyprinidae): a warm water hexamitid flagellate found in northern Europe.
AB  - The hexamitid flagellate Spironucleus vortens, previously reported from
      Pterophyllum scalare from Florida, was found in the intestine of Leuciscus idus
      in Norway. The flagellate was cultivated and studied by scanning and transmission
      electron microscopy. Identification was based on a suite of ultrastructural
      features unique for S. vortens: compound lateral ridges, a swirled posterior end,
      and a distinctive microtubular cytoskeleton. Microfibrillar structures with a
      periodicity of 0.13 microm in the right peripheral part of the compound lateral
      ridges were shown to be responsible for the distinctive rope-like appearance of
      the peripheral ridge seen in scanning electron micrographs, and not previously
      reported for S. vortens. The present results show a wide geographic distribution
      and a wide temperature tolerance for S. vortens. The flagellate was successfully
      cultivated at 5 degrees C and 15 degrees C, having previously been cultivated
      between 2-34 degrees C. Spironucleus vortens is believed to be endemic in
      Norwegian waters, but an introduction hypothesis is also discussed. The
      similarity is striking between S. vortens and S. elegans, previously described
      from amphibians and fish in Europe, and the possibility of conspecificity is
      believed to be high.

PMID- 12043962
TI  - New species of Balantidium and Paracichlidotherus (Ciliophora) inhabiting the
      intestines of four surgeonfish species from the Tuvalu Islands, Pacific Ocean.
AB  - Four species of adult herbivorous surgeonfishes (Family Acanthuridae) were
      collected from the remote South-Pacific island system of Tuvalu. Their intestinal
      contents were examined, and of four populations of ciliated protists, two new
      species were discovered and are described. Ciliates were examined after protargol
      staining and, in some cases, scanning electron microscopy. Members of each
      population were examined and 10 characters measured for the balantidia, and 13
      for the paracichlidotherids. A new Balantidium is described which has an
      unusually large dextr-oral field of cilia. A new species of Paracichlidotherus
      was discovered which has a macronucleus significantly smaller and well anteriad
      the cytoplasmic portion of the oral polykinetids relative to the type species.

PMID- 12043963
TI  - Brachiola algerae spore membrane systems, their activity during extrusion, and a
      new structural entity, the multilayered interlaced network, associated with the
      polar tube and the sporoplasm.
AB  - The microsporidial genus, Brachiola, contains three species: the type species
      Brachiola vesicularum (identified from an AIDS patient) and two species
      transferred from the genus Nosema, becoming Brachiola connori and Brachiola
      algerae. A developmental feature of the genus Brachiola is the "thickened"
      plasmalemma from sporoplasm through sporoblast stage. The sporoplasm has been
      reported to have a thick plasmalemma at 1-h postextrusion. The purpose of this
      investigation was to observe B. algerae spores before, during and after
      germination to determine if the plasmalemma is thick at the point of extrusion
      and if not, when and how it forms. New understandings regarding the polar
      filament position inside the spore, places it outside the sporoplasm proper with
      the sporoplasm limiting membrane invaginations surrounding it. These
      invaginations, present a possible location for aquaporins. The multilayered
      interlaced network (MIN), a new organelle (possibly of Golgi origin from the
      sporoblast), was observed inside the spore and sporoplasm; it formed an
      attachment to the end of the extruded polar tube and contributed to the
      thickening of the sporoplasm plasmalemma. A thin "unit limiting membrane",
      present on the sporoplasm at the time of extrusion, is connected to the MIN by
      many cross-connections forming the "thick blistered" surface by 30 min
      postextrusion.

PMID- 12043964
TI  - Changes in host and parasite-derived cellular and extracellular matrix components
      in developing cysts of Myxobolus pendula (Myxozoa).
AB  - Cysts of Myxobolus pendula from the gill arch of creek chub (Semotilus
      atromaculatus) were examined at various stages of development using light and
      electron microscopy. The subepithelial host connective tissue underwent dramatic
      changes, including degradation and remodelling of collagen and vascularisation,
      in response to the infection. Inflammatory cells lay in a fluid-filled space
      beneath the host's connective tissue and surrounded a distinctive parasite
      derived matrix, composed of collagen fibril bundles embedded in cellular
      processes of the underlying secretory cells. This collagen matrix was resistant
      to degradation and invasion by leukocytes. Secretion of a matrix by M. pendula as
      a structural support, and a protective barrier against the host inflammatory
      cells is a novel observation for cyst-forming Myxosporea.

PMID- 12043965
TI  - Analysis of expressed sequence tags (ESTs) in the ciliated protozoan Tetrahymena
      thermophila.
AB  - To assess the utility of expressed sequence tag (EST) sequencing as a method of
      gene discovery in the ciliated protozoan Tetrahymena thermophila, we have
      sequenced either the 5' or 3' ends of 157 clones chosen at random from two cDNA
      libraries constructed from the mRNA of vegetatively growing cultures. Of 116
      total non-redundant clones, 8.6% represented genes previously cloned in
      Tetrahymena. Fifty-two percent had significant identity to genes from other
      organisms represented in GenBank, of which 92% matched human proteins. Intriguing
      matches include an opioid-regulated protein, a glutamate-binding protein for an
      NMDA-receptor, and a stem-cell maintenance protein. Eleven-percent of the non
      Tetrahymena specific matches were to genes present in humans and other mammals
      but not found in other model unicellular eukaryotes, including the completely
      sequenced Saccharomyces cerevisiae. Our data reinforce the fact that Tetrahymena
      is an excellent unicellular model system for studying many aspects of animal
      biology and is poised to become an important model system for genome-scale gene
      discovery and functional analysis.

PMID- 12043966
TI  - Water quality implications of agricultural land runoff.

PMID- 12043967
TI  - Catalytically assisted electrochemical oxidation of dye Acid Red B.
AB  - This study focused on the degradation of dye Acid Red B in a catalytic
      electrolysis system with a semiconductor suspended in the electric field. The
      study showed that the addition of titanium dioxide substantially enhances the
      degradation of dye and that a semiconductor catalyst can improve electrolysis
      efficiency. This catalytic system has great potential to be applied commercially
      with the development of the catalyst. Analytical measurements show that some
      acidic compounds are produced in the treatment process and that biodegradability
      of the solution increases after electrolysis because of the breakdown of
      molecules. The UV-visible spectrum also indicates that the conjugated bonds of
      dye Acid Red B must be destroyed and that the molecules are broken into small
      ones. Furthermore, the results from the IR spectrum indicate that the nitrogen
      nitrogen double bond of dye Acid Red B must be oxidized to nitrate.
      Electrochemical measurements show an apparent dye oxidation peak from 0.65 to
      0.85 V (versus the saturated calomel electrode) in dye solution (10 g/L),
      confirming that dye is oxidized in this catalytic system.

PMID- 12043968
TI  - Attenuation of methyl tert-butyl ether in water using sunlight and a
      photocatalyst.
AB  - The use of methyl tert-butyl ether (MTBE) as a gasoline additive has resulted in
      increasing pollution of groundwater. Most of the conventional treatment
      technologies are inefficient or costly when the initial concentration of MTBE is
      low (< 200 microg/L). To find an ecology friendly and inexpensive method for MTBE
      remediation, we used solar radiation with titanium dioxide (TiO2) as a
      photocatalyst. For synthetic samples, almost complete degradation (99+%) of MTBE
      was observed at the end of 5-hour test run with 0.05 g/L of slurry TiO2.
      Intermediate products detected were tertiary butyl formate, tertiary butyl
      alcohol, and trace amounts of acetone. Studies conducted using contaminated
      groundwater samples with TiO2 and sunlight showed that aromatic organic species
      benzene, toluene, ethylbenzene, and xylenes (BTEX) were degraded up to a factor
      of 10 times faster than MTBE. However, dissolved metals (Fe2+) and chloride ions
      in contaminated waters decreased the photo-activity of TiO2 for the degradation
      of MTBE. Reducing the pH of the groundwater samples increased the MTBE
      degradation rate threefold. Photocatalysis accelerates the solar degradation of
      MTBE and reduces its half-life by more than 3 orders of magnitude. The study
      indicated that solar degradation is a low-cost and effective alternative to
      attenuate MTBE in drinking water supplies.

PMID- 12043969
TI  - Evaluation of Colilert and Enterolert defined substrate methodology for
      wastewater applications.
AB  - This study evaluated the utility of defined substrate methodology (DSM) for the
      enumeration of indicator bacteria in wastewater applications. Two commercial
      products, Colilert and Enterolert systems (Idexx Laboratories, Westbrook, Maine),
      were evaluated for variation, false-positive results, and method correlation in
      both surface waters and treated wastewater effluent. The DSM tests performed as
      well or better than the traditional methodology. The Colilert total coliform test
      was also evaluated for its utility in estimating fecal coliforms by incubation at
      44.5 +/- 0.2 degrees C. The modified DSM total coliform test correlated well to
      membrane filtration (Pearson correlation coefficient 0.8) for two different
      sample groups, demonstrating its utility as a screening tool to estimate fecal
      coliform densities.

PMID- 12043970
TI  - Removal of solids and oxygen demand from aquaculture wastewater with a
      constructed wetland system in the start-up phase.
AB  - A pilot-scale, constructed wetland system consisting of a free water surface
      (FWS) and a subsurface flow (SF) wetland operated in series was set up for
      treating aquaculture farm wastewater. This study examined the system start-up
      phenomena and evaluated its performance in removing suspended solids, algae, and
      chemical oxygen demand (COD) under various hydraulic loading rates (1.8 to 13.5
      cm/d). The SF wetland achieved stable effluent qualities without an adaptation
      period, while the FWS wetland required approximately 5 months to reach consistent
      removal levels for suspended solids and algae. Macrophyte density was a critical
      factor affecting the reduction of suspended solids and chlorophyll for the FWS
      wetland, but not for the SF wetland. Suspended solids removals in both of the
      wetlands and the combined system (47 to 86%) decreased significantly as the
      hydraulic loading rate increased, strongly following the first-order mass
      decrease equation. Phytoplankton solids (biomass and detritus) were a primary
      source of suspended solids in the aquaculture wastewater. Both chlorophyll
      reduction (76 to 95%) and COD removal (25 to 55%) in the constructed wetland
      system were apparently not affected by hydraulic loading. While algae died out
      because of limited sunlight in both wetlands, algae detritus probably still
      contributed fine particles that were difficult to remove from the water by either
      filtering or settling out. Removed suspended solids did not result in the
      increase of COD and nutrients, indicating that further solids stabilization
      occurred in the wetland system.

PMID- 12043971
TI  - Effect of varying solids concentration and organic loading on the performance of
      temperature phased anaerobic digestion process.
AB  - The effect of varying total solids (TS) and volatile solids (VS) concentrations
      and organic loading on the performance of a temperature phased anaerobic
      digestion (TPAD) system treating a mixture of primary and waste activated sludges
      was evaluated. An optimum volatile solids destruction of 61.5% occurred at a feed
      concentration of 4.9% (corresponding to 3.8% VS concentration) in the system
      operated at a total detention time of 20 days. At a total solids concentration of
      7.9% (5.8% VS concentration), the volatile solids destruction efficiency dropped
      to 52.5%. At all conditions (4.4 to 7.9% TS) the TPAD system was able to meet the
      requirements for Class A biosolids, including those for fecal coliform and
      volatile solids destruction. The effluent fecal coliform concentration never
      exceeded 628 most probable number (MPN)/g TS. Thermophilic biomass activity tests
      were run on both the thermophilic (55 degrees C) and the mesophilic (35 degrees
      C) sludge. Biomass from the thermophilic reactor showed much greater activity at
      55 degrees C than at 35 degrees C. However, significant activity was still
      present when the test was run at 35 degrees C. Activity tests completed on
      samples from the mesophilic reactor also had high activities at 55 degrees C,
      sometimes equal to the activity of the thermophilic biomass. These results
      suggest that the bacterial consortia in the TPAD system may be temperature
      tolerant and not necessarily two distinct communities with two distinct
      temperature regimes as had been previously assumed.

PMID- 12043972
TI  - Anaerobic digestion of aircraft deicing fluid wastes: interactions and toxicity
      of corrosion inhibitors and surfactants.
AB  - Corrosion inhibitors and surfactants are present in aircraft deicing fluids
      (ADFs) at significant concentrations (> 1% w/w). The purpose of this research was
      to study the interactions of a common nonionic surfactant with the commercially
      significant corrosion inhibitors used in modern ADF (4- and 5-methylbenzotriazole
      [MeBT]), and to determine the effects of their mixture on the conventional
      anaerobic digestion process. In mesophilic anaerobic microcosms codigesting
      wastewater solids, propylene glycol, and MeBT, increasing surfactant levels
      resulted in enhanced MeBT sorption on digester solids. As judged by anaerobic
      toxicity assays, responses from digesters containing surfactant concentrations
      below their critical micelle concentration (CMC) suggested that low nonionic
      surfactant concentrations could facilitate a reduction in the apparent toxicity
      of MeBT. In microcosms exposed to surfactant concentrations above their CMC, no
      increase in MeBT solubility was observed, and the anaerobic toxicity response
      corresponded to control systems not containing surfactant. Direct microscopic
      measurements of digesting biomass using fluorescent phylogenetic probes
      (fluorescent in situ hybridization) revealed that members of the domain Bacteria
      were more sensitive to MeBT in the presence of surfactant than were members of
      the domain Archaea.

PMID- 12043973
TI  - Disinfection of wastewater using a 20-kHz ultrasound unit.
AB  - The present study explored the application of a 20-kHz ultrasound unit for the
      disinfection of domestic wastewater. Experiments were conducted in batch with an
      ultrasound probe. The disinfection efficiency of fecal coliform increased with
      ultrasound power input from 0.003 log kill/min at 70 W/L to 1.8 log kill/min at
      1250 W/L. Disinfection data are well-described by the Chick-Watson disinfection
      model (coefficient of dilution, n = 2.0) using ultrasound power in place of
      chemical concentration. Water quality did not affect disinfection efficiency
      significantly. Temperature increases experienced with ultrasonic treatment were
      significant. Attempts to control the temperature resulted in a marked decrease in
      disinfection efficiency. Experiments devised to quantify the role of thermal
      mechanisms revealed that of the total kill produced by ultrasound approximately
      52% was attributed to heat, 36% to mechanical stresses associated with
      ultrasonically induced cavitation, and 12% to uncharacterized synergistic
      effects. Successful scale-up was demonstrated using a 9.3-L pilot-scale
      ultrasound unit, operated under flow-through conditions.

PMID- 12043974
TI  - Low-strength wastewater treatment using an anaerobic baffled reactor.
AB  - A 14.7-L, three-chamber anaerobic baffled reactor (ABR) was used to evaluate the
      treatment of low-strength synthetic wastewater (chemical oxygen demand [COD] of
      300 to 400 mg/L) and assess process reactivation after a prolonged period of
      inactivity. The reactor was inoculated with anaerobic seed and start-up was
      immediate. At 26 degrees C and hydraulic retention times (HRTs) of 24 and 12
      hours, COD removal averaged 87.2 and 91.0%, respectively, and biogas yield for
      methane (CH4) was 0.184 and 0.102 m3 CH4/kg COD removed, respectively. The ABR
      was reactivated after two years without feeding. Response was prompt and removal
      averaged 85.3% even during the initial 10-day period. Lowering temperature to 16
      degrees C did not impair removal efficiency at HRTs of 24 and 12 hours. However,
      biogas release decreased by 30% and apparent COD conversion to methane dropped by
      24 and 31%, respectively. At the end of the study, biomass was mostly in the
      bottom of the reactor and had moved from the first to the second chamber, while
      organic stabilization was occurring essentially in the first two chambers (56.1
      and 22.4%, respectively, in terms of COD).

PMID- 12043975
TI  - Occurrence and distribution of ammonium in Iowa groundwater.
AB  - Excess ammonium in groundwater may lead to nitrification or loss of chlorine
      residuals in public drinking water supplies. In Iowa, where groundwater supplies
      nearly 75% of all drinking water used in the state, naturally occurring ammonium
      is found in all major aquifers, including two unconsolidated units and five
      bedrock aquifers. An evaluation of ammonium concentrations in 841 municipal water
      supply wells indicated highest concentrations were found most often in Quaternary
      wells. More than one-half of all Quaternary wells sampled in Iowa showed ammonium
      concentrations greater than 2 mg/L, and more than 5% had concentrations greater
      than 5 mg/L. Nearly 5% of all bedrock wells used in this study showed ammonium
      concentrations greater than 2 mg/L. Aquifers overlain by carbon-rich
      Pennsylvanian strata or glacial drift seemed most vulnerable to elevated
      ammonium. Alluvial aquifers were least vulnerable to elevated ammonium
      concentrations in Iowa municipal water supplies. Ammonium concentrations tended
      to be higher in wells that screened groundwater containing more dissolved solids,
      including sulfate, chloride and iron.

PMID- 12043976
TI  - The effectiveness of bioaugmentation in nitrifying systems stressed by a washout
      condition and cold temperature.
AB  - Bioaugmentation consists of adding selected strains of microorganisms with known
      capabilities to a biological process to improve performance. In this study,
      laboratory-scale completely stirred tank reactors were bioaugmented with
      nitrifying bacteria while operated under high-stress conditions for the
      nitrifiers: a 2-day solids retention time (SRT) at 22 degrees C or a 5-day SRT at
      4 degrees C. Intensive sampling was carried out to document the effects of the
      bioaugmentation. To quantitatively interpret the effects of biomass addition on
      process performance, mathematical modeling was carried out. Experimental and
      modeling results indicate that the maximum effect of a one-time bioaugmentation
      depend on the dose and decays as bioaugmented nitrifiers are washed out. Daily
      maintenance dosing results in long-term good performance, provided that the dose
      is large enough. For severe stress, almost all of the biomass in the system must
      be added by bioaugmentation.

PMID- 12043977
TI  - Empirical equations for the limiting solids flux of final clarifiers.
AB  - Using the solids flux theory, two quantities (i.e., the dimensionless limiting
      solids flux [G = kGL/v(o)] and the dimensionless underflow velocity [U =
      FR/(Av(o))] are introduced for a final clarifier based on the Vesilind equation
      of sludge zone-settling velocity (v = v(o) exp[-kX], where X is the suspended
      solids concentration, v(o) and k are empirical coefficients, and GL, FR, and A
      are the limiting solids flux, recycle flowrate, and surface area of the settling
      tank, respectively). In this paper, the dimensionless limiting solids flux is
      shown to be a function of the dimensionless underflow velocity only and is
      accurately represented by empirical equations. The limiting solids flux can,
      thus, be easily calculated by using the empirical equations without resorting to
      tedious numerical procedures. Furthermore, using the dimensionless quantities (G
      and U), two final clarifier equations that express the relationship among
      suspended solids concentration, surface area of the clarifier, recycle flowrate,
      and wastewater flowrate are derived. Their applications to final clarifier
      analysis and to determining required surface area of final clarifier are
      illustrated.

PMID- 12043978
TI  - Discussion of: Microfiltration of municipal wastewater for disinfection and
      advanced phosphorus removal: results from trials with different small-scale pilot
      plants, R. Gnirss, J. Dittrich, 72, 602 (2000).

PMID- 12043980
TI  - Autologous osteochondral grafting for talar cartilage defects.
AB  - The purpose of this study was to evaluate the clinical results of Osteochondral
      Autograft Transfer System (OATS) for the treatment of symptomatic osteochondral
      defects of the talus using standardized outcome analysis. Nineteen patients with
      symptomatic osteochondral defect (OCD) of the talus were treated with autologous
      osteochondral grafting. There were six men and 13 women. The average age was 32
      years (range, 18 to 48 years). The average duration of symptoms prior to surgery
      was 4.2 years (range, three months to 12 years). All patients had failed
      nonoperative treatment, and 13 (68%) patients had failed prior excision,
      curettage and/or drilling of the lesion. The average size of the lesion prior to
      autografting was 12 mm x 10 mm (range, 10 x 5 mm to 20 x 20 mm). Donor plugs were
      harvested from the trochlear border of the ipsilateral femoral condyle. Ankle
      exposure was obtained with a medial malleolar osteotomy in 13 patients,
      arthrotomy in five patients and lateral malleolar osteotomy in one patient.
      Clinical evaluations were performed for both the recipient ankle and donor knee
      using the AOFAS Ankle/Hindfoot Scale and Lysholm knee scale, respectively. The
      average follow-up time was 16 months (range, 12 to 30 months). The average
      postoperative AOFAS ankle score was 88 (range, 60 to 100). Most patients had
      occasional mild pain, but excellent function, range of motion, stability and
      alignment. The average postoperative ankle score for the 13 patients who failed
      prior surgery was 91 (range, 84 to 100). The average postoperative Lysholm knee
      score was 97 (range, 87 to 100). Only two patients had mild knee pain.
      Postoperative radiographs were available for 13 patients. There was no evidence
      of graft subsidence and all grafts healed. All malleolar osteotomies united.
      Seventeen (89%) patients said that they would undergo the procedure again. The
      results of osteochondral autograft transplant for OCD lesions of the talus
      demonstrate excellent postoperative ankle scores including improvement of pain
      and function with minimal knee donor site morbidity. Also, our results indicate
      that this is an effective salvage procedure following failed previous procedures
      and for patients with longstanding symptoms.

PMID- 12043981
TI  - Arthrodesis of the ankle for non-inflammatory conditions--healing and reliability
      of outcome measurements.
AB  - This is a retrospective study of 30 consecutive primary ankle arthrodeses in 29
      patients with osteoarthrosis, operated on in our hospital between 1984 and 1994.
      Two different techniques were utilized: internal fixation with screws or external
      fixation using Charnley or Hoffman frames. Only 25 ankles in 24 patients were
      available for clinical examination. They were examined by two independent
      surgeons on an average of 51 months after surgery (13 to 187 months). Two
      radiologists separately examined the radiographs that were available--in this
      case, 29 ankles, without knowledge of clinical data, and 26/29 (89%) were
      unanimously considered as fused. This is comparable with what is reported in
      other series. Unanimity among all four observers regarding healing of the
      arthrodesis occurred in 20/25 ankles (80%). We consider that both a radiological
      and a clinical evaluation is important for a fair judgement of fusion. We found
      high consistency among the observers with respect to the clinical scores.
      However, the consistency was somewhat better for the Mazur than for the Kofoed
      system.

PMID- 12043982
TI  - Safety and efficacy of the popliteal fossa nerve block when utilized for foot and
      ankle surgery.
AB  - The popliteal fossa nerve block (PFNB) offers numerous advantages that make it a
      suitable anesthetic technique for foot and ankle surgery. In this retrospective
      study, we investigated the acute and long-term safety and efficacy of this
      relatively underutilized anesthetic technique for foot and ankle surgery. A
      review of 834 patients who underwent foot and/or ankle surgery by the coauthor
      (NAA) was conducted. Four hundred sixty-seven patients received a PFNB with the
      aid of a peripheral nerve stimulator. Variables assessed included the quality of
      surgical anesthesia, postoperative analgesia and the acute and long-term
      incidence of postoperative neuralgia and neuropraxia. The PFNBs were performed by
      anesthesiologists with various levels of training at a tertiary care hospital and
      all were supplemented with a saphenous nerve block. The PFNB was successful as
      the sole anesthetic technique in 79% of the cases; 18% were converted to general
      anesthesia and 3% required augmentation with local anesthetic. There were no
      complications associated with the PFNB. There were no incidents of postoperative
      neuralgia or neuropraxia. Only 12% of patients with a successful block required
      analgesics in the PACU, while 60% of patients with a failed block required
      systemic analgesics for surgical site pain (p<0.01). These results suggest that
      the performance of the PFNB with the guidance of a peripheral nerve stimulator is
      a safe and effective anesthetic technique for foot and ankle surgery.

PMID- 12043983
TI  - Two modifications of the Weil osteotomy: analysis on sawbone models.
AB  - Second metatarsal osteotomies (30 degrees angle to shaft) were performed in 40
      sawbones with: 1. head shifted proximally 5 mm; 2. head shifted proximally 10 mm;
      3. 5-mm slice resected and head shifted proximally 5 mm; or 4. 5-mm dorsally
      based wedge resected and head shifted proximally 5 mm. Bone slice resection
      resulted in shortening (16.4+/-1.7 mm) and mild plantar displacement of the head
      (3.5+/-0.8 mm). Bone wedge excision resulted in moderate shortening (7.8+/-0.9
      mm) and essentially no plantar displacement of the head (0.8+/-1.4 mm).

PMID- 12043984
TI  - Pulmonary embolism following operative treatment of ankle fractures: a report of
      three cases and review of the literature.
AB  - The risks of thromboembolism following operative treatment of ankle fractures are
      deep vein thrombosis (DVT) and pulmonary embolism (PE). These are potentially
      life-threatening complications. Many orthopedic surgeons fail to appreciate the
      potential complications of thromboembolic events because of their rare and
      delayed occurrence in foot and ankle operations. The purpose of this report is to
      describe the potential for DVT and PE following ankle operations. We present
      three cases in which patients who underwent operative treatment of ankle
      fractures subsequently developed PE. We also review the literature on the
      prevalence of thrombosis, risk factors, methods of prophylaxis, and use of
      prophylaxis in surgical procedures of the lower extremity.

PMID- 12043985
TI  - Incidence of DVT following surgery of the foot and ankle.
AB  - A prospective study was undertaken to establish the incidence of deep vein
      thrombosis (DVT) in patients who had undergone surgery of the foot and ankle. All
      consecutive patients who underwent foot and ankle surgery in the senior author's
      practice had duplex ultrasound performed of the bilateral calves at the first
      postoperative visit. Of 201 patients, deep calf clots were found in seven
      patients (3.5%), but none of these showed progression on follow-up ultrasound or
      extension proximal to the calf. By the authors' criteria, none of the studied
      patients required treatment. The authors feel that the rate and progression of
      DVT after foot and ankle surgery is low and does not require routine prophylaxis.
      Factors associated with risk of DVT formation were postoperative immobilization,
      hindfoot surgery, tourniquet time and advancing age.

PMID- 12043986
TI  - The surgical management of central metatarsalgia.
AB  - Seventeen patients (20 feet) underwent Weil osteotomies of the second and third
      metatarsals for the treatment of central metatarsalgia and were reviewed at an
      average of 18 months postoperatively. Fourteen patients were completely satisfied
      with the results of their surgery (85%), one patient was satisfied, one patient
      satisfied with reservations and one patient was dissatisfied. The American
      Orthopaedic Foot and Ankle Society clinical rating scale improved by an average
      of 44 points. One patient had complete recurrence of symptoms, eight out of the
      40 toes involved in surgery were floating, four toes were stiff, there were three
      cases of infection, and transfer metatarsalgia affected the fourth metatarsal in
      one case. The Weil osteotomy is an effective and safe procedure for the treatment
      of central metatarsalgia.

PMID- 12043987
TI  - The transverse dorsal approach to the Lisfranc joint.
AB  - While multiple longitudinal skin incisions can be utilized to visualize the
      joints of the midfoot, we feel that exposure can be difficult. Dorsal transverse
      and T incisions were undertaken to expose the tarsometatarsal joints (TMTJs) in
      12 patients. Five of the 12 had some form of immunosuppression, including
      diabetes, methotrexate therapy and antirejection transplant therapy. One patient
      who had a lengthening of the midfoot with a structural autograft suffered a small
      area of skin necrosis that healed by secondary intention. The remainder of
      patient's wounds healed without complication. Three to six dorsal access
      intervals are created between the neurovascular and musculotendinous structures
      that overlie the TMTJs. The transverse incision can be extended into a medially
      based T incision to apply a medial plate as required. Transverse incisions are
      not recommended for patients who require lengthening of the midfoot.

PMID- 12043988
TI  - Correcting and lengthening of metatarsal deformity with circular fixator by
      distraction osteotomy: a case of longitudinal epiphyseal bracket.
AB  - The condition known as longitudinal epiphyseal bracket or delta phalanx is a rare
      congenital anomaly that affects the tubular bones of hand or foot. Metatarsal
      epiphyseal bracket restrains longitudinal growth, causing progressive deformity
      and resulting in a short, broad metatarsal and a medially deviated
      metatarsophalangeal joint and hallux magnus. Although there are some case series
      describing metatarsal lengthening with the unilateral fixator in the literature,
      we could not find any case that combines both metatarsal lengthening and
      deformity correction with the circular external fixator. Gradual lengthening and
      deformity correction without bone grafting and soft-tissue modification were
      carried out in a case with bilateral longitudinal epiphyseal bracket of the first
      metatarsals of the foot. A literature review and treatment method for epiphyseal
      bracket in a 9-year-old boy is presented. Excellent clinical, and functional
      results were obtained with circular and semicircular fixators.

PMID- 12043989
TI  - Forefoot narrowing with external fixation for problem cleft wounds.
AB  - Healing of forefoot cleft wounds can be a difficult management problem in
      patients with peripheral vascular disease, diabetes or both. This is a
      prospective review of 15 patients with these conditions with nonhealing middle
      ray cleft wounds managed with a temporary mini-external fixator to close the
      cleft wound. Fourteen (93%) of the 15 patients had a successful obliteration of
      the cleft and skin coverage. Twelve (80%) of 15 were able to resume their
      previous level of activity with the reconstructed, mechanically sound forefoot.
      Fourteen (93%) of the 15 patients received hyperbaric oxygen treatments as an
      adjunct to wound healing. All patients avoided a transmetatarsal or higher
      amputation.

PMID- 12043990
TI  - Tendon arthroplasty for basal fourth and fifth metatarsal arthritis.
AB  - Arthritis of the fourth and fifth tarsometatarsal joints, recalcitrant to
      nonoperative treatment, presents a difficult clinical situation. As part of the
      lateral rays, these joints have considerable motion, making fusion a very
      disabling operation. Between 1990 and 1998, 12 patients, who had failed
      nonoperative treatment, underwent resection arthroplasty of the base of the fifth
      or fourth and fifth metatarsals with tendon interposition. Preoperative
      differential injections had confirmed the source of pain in eight cases. Patients
      were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS)
      midfoot scale; a visual analogue scale to assess perception of pain and
      disability; a satisfaction index; and, where possible, a comprehensive physical
      examination. At an average of 25 months follow-up, the average AOFAS score was
      64.5. On the visual analogue scale, pain improved an average of 35% and
      disability improved 10%. Six of the eight patients who participated in this study
      were satisfied with the operation and would undergo the procedure again for
      similar symptoms. Patients with a higher postoperative score on the AOFAS midfoot
      rating scale were statistically more likely to have had a positive differential
      injection preoperatively. We believe a lateral column tarsometatarsal resection
      arthroplasty is an effective salvage operation when lateral column midfoot
      arthritis is confirmed by differential injection and nonoperative measures have
      provided inadequate relief.

PMID- 12043991
TI  - Bone marrow edema of the forefoot after chevron osteotomy--a rare cause of
      metatarsalgia: a case report.
AB  - Treatment options of bone marrow edema syndrome, which is associated with
      vascular disturbances, are protracted nonoperative treatment or core
      decompression which still demands several weeks until complete recovery. We
      obtained excellent results by the use of the vasoactive drug iloprost, a stable
      prostacyclin analogue, leading to a complete relief of symptoms in cases of bone
      marrow edema which had initially suggested early avascular necrosis of the second
      metatarsal head. The bone marrow edema of the second metatarsal bone was thought
      to be due to altered biomechanics following a distal first metatarsal chevron
      osteotomy. During the five days of iloprost infusion, the patient reported relief
      of rest pain. After therapy, the pedobarogram was normalized. The AOFAS forefoot
      score improved from 44 to 85 points after one month, and to 95 points after three
      months. At that time, the marrow showed normal signals. Without additional
      intervention the patient was able to resume normal activities.

PMID- 12043992
TI  - A biomechanical study of two postoperative prostheses for transtibial amputees: a
      custom-molded and a prefabricated adjustable pneumatic prosthesis.
AB  - We evaluated an adjustable pneumatic prefabricated prosthesis and a rigid custom
      molded prosthesis for immediate postoperative use. Twelve transtibial amputations
      were performed on cadaver limbs. Differential variable reluctance transducers
      were placed subcutaneously across the wound edge medially and laterally. The
      limbs were then placed in either the pneumatic prosthesis (five limbs) or the
      rigid prosthesis (seven limbs). The specimens underwent static and cyclic loading
      to simulate weight bearing. The strain readings for static and cyclic loading
      were greater in the rigid prosthetic group. Only the mean medial strain
      measurement after cyclic loading was statistically significant. The results
      demonstrate that the pneumatic prosthesis places less strain across the wound
      than a rigid prosthesis.

PMID- 12043993
TI  - An efficient gel-phase synthesis of peptides on a high capacity flexible
      crosslinked polystyrene support: comparison with Merrifield resin.
AB  - A highly solvating copolymer was prepared in high yield by introducing a flexible
      crosslinker, 1,4-butanedioldimethacrylate, into the polystyrene matrix by a free
      radical aqueous suspension polymerization. A 2 mol% crosslinked resin showed
      rigidity and mechanical characteristics comparable to those of divinylbenzene
      crosslinked polystyrene (Merrifield resin, DVB-PS) support. Swelling and
      solvation characteristics of the new resin, BDDMA-PS, were much higher than DVB
      PS support in all solvents used for solid phase peptide synthesis. The diacrylate
      crosslinks in the resin network were found to be highly stable even after 48 h
      treatment with neat TFA, 6 N HCl and 6 N KOH at 110 degrees C. To demonstrate the
      usefulness of the new resin in high capacity peptide synthesis, a typical
      difficult peptide, acyl carrier protein (ACP) fragment (65-74), was synthesized
      on commercially available 1 mol% crosslinked DVB-PS and 2 mol% crosslinked BDDMA
      PS resins under identical conditions. A protocol using NMP/DMSO mediated coupling
      was employed for chain assembly. The yield and purity of the product from BDDMA
      PS resin was higher than when the DVB-PS resin was used. The mechanistic reason
      behind the synthetic efficiency of the new resin was found to be its ability to
      induce random coil conformation to the growing peptide chains.

PMID- 12043994
TI  - Synthesis of heterotrimeric collagen peptides containing the alpha1beta1 integrin
      recognition site of collagen type IV.
AB  - Collagen type IV provides a biomechanically stable scaffold into which the other
      constituents of basement membranes are incorporated, but it also plays an
      important role in cell adhesion. This occurs with collagen type IV mainly via the
      alpha1beta1 integrin, and the proposed epitope involved in this type of
      collagen/integrin interaction corresponds to a non-sequential R/Xaa/D motif,
      where the arginine and aspartate residues are provided by the alpha2 and alpha1
      chains of the collagen molecule, respectively. Since the stagger of the three
      alpha chains in native collagen type IV is still unknown and different alignments
      of the chains lead to different spatial epitopes, two heterotrimeric collagen
      peptides containing the natural 457-469 sequences of the cell adhesion site were
      synthesized in which the single chains were assembled via disulfide bonds into
      the two most plausible alpha1alpha2alpha1' and alpha2alpha1alpha1' registers. The
      differentiated triple-helical stabilities of the two heterotrimers suggest a
      significant structural role of the chain register in collagen, although the
      binding to alpha1beta1 integrin is apparently less affected as indicated by
      preliminary experiments.

PMID- 12043995
TI  - Conformation-dependent side reactions in interstrand-disulfide bridging of
      trimeric collagenous peptides by regioselective cysteine chemistry.
AB  - Conversion of single-chain or disulfide-bridged dimeric collagenous peptides into
      Cys(Npys) derivatives as activated species for subsequent regioselective
      thiol/disulfide exchange reactions leads to side products whose origin and nature
      was determined by HPLC and ESI-MS. In both cases the high tendency of the educts
      to self-associate into triple-helical homotrimers, as assessed by their dichroic
      properties in the reaction media, is responsible for the failure of this well
      established cysteine chemistry. Only by optimizing the synthetic strategy or by
      exploiting a kinetic control of the reaction, could these conformation-dependent
      limitations be more or less efficiently bypassed for the regioselective assembly
      of heterotrimeric collagen model peptides crosslinked with artificial cystine
      knots.

PMID- 12043996
TI  - Conformational solution studies of neuropeptide gamma using CD and NMR
      spectroscopy.
AB  - Neuropeptide gamma is one of the largest members of the tachykinin family of
      peptides, exhibiting strong agonistic activity towards the NK-2 tachykinin
      receptor. This peptide was synthesized by the solid-phase method using the Fmoc
      chemistry. Circular-dichroism spectroscopy (CD) investigations of this peptide
      were performed in phosphate buffer, in the presence of sodium dodecylsulphate
      (SDS) micelles and trifluoroethanol (TFE) solutions and in DMSO-d6 using the 2D
      NMR technique in conjunction with two different theoretical approaches. The first
      assumes multiconformational equilibrium of the peptide studied characterized by
      the values of statistical weights of low-energy conformations. These calculations
      were performed using three different force fields ECEPP/3, AMBER4.1 and CHARMM
      (implemented in the X-PLOR program). The second method incorporates interproton
      distance and dihedral angle constraints into the starting conformation using the
      Simulated Annealing algorithm (X-PLOR program). The CD experiments revealed that
      although the peptide studied is flexible in polar solvents, a tendency to adopt a
      helical structure was observed in the hydrophobic environment. The NMR data (NOE
      effects) indicate a helical or reverse structure in the Ile7-His12 fragment of
      the peptide studied in DMSO-d6 solution. The results obtained cannot be
      interpreted in terms of a single conformation. Most of the conformations obtained
      with the ECEPP/3 force field possess a high content of a helical structure. None
      of the conformers, obtained with the AMBER4.1 and CHARMM force fields, can be
      considered as the dominant one. In all conformations several beta-turns were
      detected and in some cases gamma-turns were also found. But in fact, it is rather
      difficult to select the position of the secondary element(s) present in the
      structure of NPgamma in solution. All conformers calculated with the X-PLOR
      program (with using NMR derived distance and torsion angle constraints) are
      stabilized by several beta-turns. Common structural motives are a type IV beta
      turn in the Gln6-His12 fragment. All conformations obtained using two approaches
      adopt very similar turn shapes in the middle region of molecule and a random
      structure on the N- and C-terminal fragments.

PMID- 12043997
TI  - A colorimetric enzyme-linked on-bead assay for identification of synthetic
      substrates of protein tyrosine kinases.
AB  - Protein tyrosine kinases play key roles in the progression of numerous human
      diseases including several types of cancers. We report here a simple colorimetric
      assay for tyrosine kinase activity employing synthetic peptide substrates
      prepared on Tentagel synthesis beads. Phosphorylation of compounds on beads was
      detected with an antiphosphotyrosine antibody complexed with a secondary antibody
      alkaline phosphatase conjugate. This assay may prove useful for the
      identification and characterization of synthetic substrates of this important
      class of enzymes.

PMID- 12043998
TI  - New Zealand's HIV infected population under active follow-up during 2000.
AB  - AIM: To audit New Zealand's HIV infected population currently under active follow
      up. METHODS: Multiple sources were used to determine anonymously the demographic
      and management characteristics of HIV infected individuals being monitored with
      HIV viral load measurements and/or receiving antiretroviral therapy during 2000.
      RESULTS: 593 people (480 males and 113 females) were under active follow-up. The
      most common transmission risk was male homosexual contact (56%) followed by
      heterosexual contact (28%), injecting drug use (3%) and mother to infant
      transmission (1%). Ethnicity data showed a disproportionate number of Africans
      (13%) compared to recent census figures. Anti-retroviral therapy was used in 71%
      of the cohort of whom 62% had HIV viral load measurements below 400 copies/mL. An
      upper estimate of diagnosed HIV individuals living in New Zealand at 30/9/2000
      was 801. CONCLUSIONS: This is the first time that the demographic and clinical
      state of HIV infected individuals has been assessed throughout New Zealand. The
      results suggest a slightly lower number of HIV infected individuals currently
      living in New Zealand than previously estimated. Anti-retroviral therapy is being
      used effectively within the HIV infected population. The changing demographics,
      with a higher proportion of people under care from Africa, increasing numbers of
      females, and an increase in the proportion with heterosexual risk factors are
      particular challenges.

PMID- 12044000
TI  - Ethnic and gender differences in the use of coronary artery revascularisation
      procedures in New Zealand.
AB  - AIMS: To examine ethnic and gender variations in the use of coronary artery
      revascularisation procedures in New Zealand and to determine whether the
      introduction of priority scores affected intervention trends. METHODS: Analysis
      of the National Minimum Database for coronary artery bypass graft (CABG) and
      percutaneous transluminal coronary angioplasty (PTCA) intervention rates for New
      Zealand Pacific, Maori and other men and women aged 40 years and over during the
      decade 1990-1999. RESULTS: Coronary artery revascularisation rates were lower in
      women than in men in all ethnic groups and in Pacific and Maori men compared with
      other New Zealand men. Compared to all men, the mean age-standardised CABG and
      PTCA intervention rate ratios in all women were 0.34 and 0.36. Compared to other
      New Zealand men, the mean age-standardised CABG and PTCA intervention rate ratios
      were 0.64 and 0.25 in Pacific and 0.40 and 0.29 in Maori men respectively.
      Compared to other New Zealand women, the rate ratios for CABG and PTCA were 0.73
      and 0.21 in Pacific and 0.74 and 0.43 in Maori women respectively. Introducing
      priority scores was neither associated with reduced cardiac procedures nor
      significantly reduced variation in procedures across all ethnic groups.
      CONCLUSIONS: Although Pacific and Maori peoples had higher rates of coronary
      artery disease morbidity and mortality, revascularisation rates were lower in
      both groups. Strategies beyond the use of priority scores are needed to address
      ethnic and gender disparities in coronary artery revascularisation procedures in
      New Zealand.

PMID- 12043999
TI  - Depression in patients in an Auckland general practice.
AB  - AIM: To measure the rate of detected and undetected depression in patients
      attending an Auckland general practice. METHOD: At their consultation conclusion,
      general practitioners (GPs) asked all consecutive patients over sixteen years
      attending for consultation to participate in a health and mood questionnaire. A
      researcher administered the Beck Depression Inventory (BDI) to consenting
      participants. The GPs previously recorded whether they considered these patients
      depressed. RESULTS: Response rate among patients was 81% (253/314). The BDI found
      a 13.8% (35/253) 95% CI (9.6-18.5) depression prevalence among patients. GPs
      picked up 51% of cases (sensitivity 0.51 and specificity 0.91). Maori patients
      were no more likely to be depressed than non-Maori but they were less likely to
      be receiving or have received treatment with antidepressants. CONCLUSION: The
      rate of depression in this practice was higher than an earlier study suggesting
      the true rate may be >10%. GPs see more depressed patients than other health
      professionals, therefore improvement in detection and management of depression in
      primary care is important. More work is needed on the difference between Maori
      and non-Maori in the use of antidepressants.

PMID- 12044001
TI  - Seasonal variation, hip fracture and vitamin D levels in Southern Tasmania.
AB  - AIMS: To determine the frequency of vitamin D deficiency in older patients
      admitted with a hip fracture and to look for seasonal variation in vitamin D
      levels and hip fracture in Southern Tasmania. METHODS: This was a case series of
      patients admitted to the Royal Hobart Hospital, Tasmania with a hip fracture from
      July 1996-June 1997. Information was collected on demographic data, functional
      activity, associated medical disorders and drug history. RESULTS: There were 91
      patients, 66 female with a mean age of 81.3 years. Vitamin D deficiency, defined
      as a serum 1,25 hydroxyvitamin D level <28 nmol/L was present in 67% of subjects.
      Vitamin D levels were low throughout the year without significant seasonal
      variation. There was no seasonal variation in admissions with a hip fracture. The
      majority of patients (68%) either lived in institutional care or were dependent
      on a carer and 43% reported going outdoors less than once a week. CONCLUSIONS:
      The high incidence of vitamin D deficiency in these subjects admitted with a hip
      fracture reflects reduced sunlight exposure and poor diet and is probably a
      marker of frailty. The absence of seasonal variation reflects a frailer
      population likely to be housebound, less mobile and more likely to have falls and
      sustain a fracture. Older and frailer people may benefit from routine screening
      for vitamin D deficiency, and replacement therapy should be considered for those
      found to be deficient.

PMID- 12044003
TI  - Metabolic disease: a multitude of presentations.

PMID- 12044002
TI  - Mortality and cancer incidence in New Zealand pulp and paper mill workers.
AB  - AIMS: To evaluate mortality and cancer incidence in a cohort of workers employed
      in the New Zealand pulp and paper industry, and to identify the exposures
      responsible for any increased risk. METHODS: A total of 8456 workers employed for
      at least one year in three pulp and paper mills between 1978 and 1990 were
      followed up until 1992. The observed number of deaths and cancer cases was
      compared with expected numbers calculated using five-year age-specific rates for
      the New Zealand population. RESULTS: Vital status was determined for 81% of the
      cohort, and for 93% of the total person-years at risk. Mortality from all causes
      (standardised mortality ratios (SMR) = 0.80, 95% confidence intervals [CI] 0.71
      0.89; 314 deaths), and from all malignant neoplasms (SMR = 0.95, 95% CI 0.78
      1.15, 103 deaths), was lower than expected. Mortality from lung cancer (SMR =
      1.33, 95% CI 0.94-1.83, 37 deaths) was marginally increased. CONCLUSIONS: No
      overall increase in mortality from cancer or other causes was observed in this
      cohort. A small increase in lung cancer risk is suggested, although this was not
      statistically significant. Numbers of cases were too small for detailed analyses
      of associations between disease and specific exposures.

PMID- 12044004
TI  - Positional upper airways narrowing and an apparent life threatening event.

PMID- 12044005
TI  - Screening for type 2 diabetes in non-pregnant adults in New Zealand: practice
      recommendations.

PMID- 12044007
TI  - On the death of John David Reid.

PMID- 12044006
TI  - Cardiovascular disease and lipid management in New Zealand: progress at last!

PMID- 12044008
TI  - Journal article on smoking and blindness prompts significantly more calls to the
      Quitline.

PMID- 12044009
TI  - Modelling the molecular circuitry of cancer.
AB  - Cancer arises from a stepwise accumulation of genetic changes that liberates
      neoplastic cells from the homeostatic mechanisms that govern normal cell
      proliferation. In humans, at least four to six mutations are required to reach
      this state, but fewer seem to be required in mice. By rationalizing the shared
      and unique elements of human and mouse models of cancer, we should be able to
      identify the molecular circuits that function differently in humans and mice, and
      use this knowledge to improve existing models of cancer.

PMID- 12044010
TI  - Papillomaviruses and cancer: from basic studies to clinical application.
AB  - Links between human papillomaviruses (HPVs) and cervical cancer were first
      suspected almost 30 years ago. DNA of specific HPV types has since been found in
      almost all cervical cancer biopsies. HPV oncogenes that are expressed in these
      cells are involved in their transformation and immortalization, and are required
      for the progression towards malignancy. Epidemiological studies have underlined
      that HPVs are the main aetiological factor for cervical cancer. But how has this
      knowledge been translated into the clinic to allow the prevention, screening and
      treatment of cervical cancer?

PMID- 12044011
TI  - Oncogenic tyrosine kinases and the DNA-damage response.
AB  - Oncogenic tyrosine kinases (OTKs) are involved in the induction of many types of
      tumour, including haematological malignancies and cancers of the breast,
      prostate, colon and lung. Neoplastic cells that express OTKs are usually
      resistant to apoptosis that is induced by DNA-damaging agents, such as cytostatic
      drugs and irradiation, and they display genomic instability. So, what are the
      mechanisms involved, and what is the potential for overcoming OTK-mediated
      resistance in the clinic?

PMID- 12044012
TI  - Gli and hedgehog in cancer: tumours, embryos and stem cells.
AB  - Do tumours arise from stem cells, or are they derived from more differentiated
      cells that, for some reason, begin to recapitulate developmental programmes?
      Inappropriate activation of the Sonic hedgehog-Gli signalling pathway occurs in
      several types of tumour, including those of the brain and the skin. Studies in
      these and other systems suggest that inappropriate function of the Gli
      transcription factors in stem or precursor cells might lead to the onset of a
      tumorigenic programme and that these factors are prime targets for anticancer
      therapies.

PMID- 12044013
TI  - AIDS-related malignancies.
AB  - Cancer remains a significant burden for human immunodeficiency virus (HIV)
      infected individuals. Most cancers that are associated with HIV infection are
      driven by oncogenic viruses, such as Epstein-Barr virus, Kaposi's sarcoma
      associated herpesvirus and human papillomavirus. Gaining insight into the
      epidemiology and mechanisms that underlie AIDS-related cancers has provided us
      with a better understanding of cancer immunity and viral oncogenesis.

PMID- 12044014
TI  - Effects of psychotherapy on cancer survival.
AB  - The possibility that psychotherapy could extend survival time for cancer patients
      has attracted attention among clinical investigators interested in the mind-body
      connection, among cancer patients seeking the best possible outcome and among the
      general public. A small number of randomized trials have been conducted, and they
      have produced conflicting results. Does emotional support affect the course of
      cancer? What physiological pathways might mediate such an effect? Given what we
      now know, should we change the standard of care for cancer patients?

PMID- 12044016
TI  - Scientific bases of acupuncture analgesia.
AB  - The present paper was to review the physiological bases of acupuncture analgesia
      (AA) on normal subjects, patients, and animals. Effect of acupuncture on pain
      perception in normal subjects was studied and compared with sham acupuncture. It
      was shown that the analgesic effect of acupuncture has its physiological basis.
      Using neurophysiological, neuropharmacological, neurobiochemical and
      neuromorphological methods, the neurohumoral mechanism of AA was studied from the
      peripheral neural pathway of acupuncture sensation (De-Qi sensation in Chinese
      traditional medicine) to the central neuromodulatory effect of AA. It was
      indicated that needling of acupuncture point could activate the afferent fibers
      of peripheral nerves to elicit De-Qi sensation, then ascended mainly through the
      ventro-lateral funiculi, which conducted pain and temperature sensation upward to
      the brain, activated the antinociceptive system including certain brain nuclei.
      modulators (opioid peptides), neurotransmitters, through the descending
      inhibitory pathway resulting in analgesia. Especially the clinical and laboratory
      results indicated that the endogenous opiate peptides (EOP) participated in AA
      from the presynaptic level to the receptor sites, which provided a scientific
      basis for understanding the mechanism of AA. Substantial evidences have been
      accumulated that acupuncture has prominent analgesic effect; but it fails to give
      sufficient analgesia during operation. Some effective measures to improve the
      therapeutic effect of acupuncture, such as the combination of acupuncture with
      drugs, the selection of suitable EA parameters and optimal time spacing should be
      adopted.

PMID- 12044015
TI  - A history of prostate cancer treatment.
AB  - The increased incidence of prostate cancer has led to remarkable changes in
      diagnosis and treatment over the past century. What were the first ways in which
      prostate cancer was treated, and how did these evolve into the variety of
      therapeutic strategies from which patients have to choose today?

PMID- 12044017
TI  - Neuroimmunal regulation of electroacupuncture (EA) on the traumatic rats.
AB  - EA has a wide range of function, many of them is mediated by the release of the
      endogenous opioid peptides. Using surgical traumatic stress model, it was
      observed that EA could improve the depression of cell mediated immune response.
      Based on the above results, we focused our work on the elucidation of the
      mechanism of EA in the central nervous system. The results showed that trauma
      amplified the activity of peritoneal macrophage, but inhibited Orphanin FQ and
      its receptor NP4 transcripts in the central nervous system, in the mean time, IL
      1beta transcripts in the central nervous system was also augmented. EA
      stimulation of"Zusanli" (St. 36) and "Lanwei" (Extra. 37) points could inhibit
      all the above responses, but it had no influence on the normal rat. The results
      suggested that EA could modulate immune response via the interaction between
      Orphanin FQ and IL-1beta.

PMID- 12044018
TI  - Effect of electroacupuncture on the expression of interlukin-1beta mRNA after
      transient focal cerebral ischemia.
AB  - It has been reported that interleukin-1beta (IL-1beta ) play a key role in the
      pathogenesis of cerebral ischemia. Acupuncture is an effective traditional
      medical therapy in China. The aim of present study was to evaluate the effect of
      electroacupuncture (EA) on IL-1beta mRNA expression after middle cerebral artery
      occlusion (MCAO) in rats. Using in situ hybridization technique, it was found
      that in the MCAO group the expression of IL-1beta mRNA was significantly
      increased at 2h, 6h, 12h after reperfusion in cerebral ischemic cortex compared
      with normal group. In EA+ MCAO group the expression of IL-1beta mRNA was
      significantly decreased at 2h, 6h and 12h in ischemic cortex compared with MCAO
      group. The results indicated that EA might decrease the IL-1beta protein
      expression by reducing the IL-beta mRNA expression in ischemic cortex.

PMID- 12044019
TI  - Intravaginal surface EMG probe design test for urinary incontinence patients.
AB  - Pelvic floor training is a well-established treatment for female urinary stress
      incontinence The purpose of this study was to test four different intravaginal
      surface electromyography (EMG) probes for biofeedback exercise and measurements.
      The study design was a comparison test. The study was accomplished in a referral
      on outpatient clinic. Participants were 9 urinary incontinent patients sent to
      physiotherapist for pelvic floor muscle exercise and 2 asymptomatic volunteers.
      The participants were asked to do pelvic floor contractions in supine position.
      The EMG activity of pelvic floor muscles was measured with four different types
      of intravaginal probes, and rectal pressure was measured simultaneously with a
      microtip catheter for controlling the pelvic floor muscle contraction force
      levels. Main outcome measure was the electrical activity of pelvic floor muscle
      contractions. The intraprobe correlation coefficients for comparing subsequent
      measurements ranged from 0.84-0.97, indicating adequate reliability. The results
      were affected by the location of the measuring electrodes, and the shape and size
      of the probes. No statistically significant differences were found between
      different probes. The compliance was best with L- shaped probe B and it gave
      highest mean EMG values so it was chosen for M- further development as a
      biofeedback-based home training system.

PMID- 12044020
TI  - The neuroprotective effects of electroacupuncture on focal cerebral ischemia in
      monkey.
AB  - The present study was designed to investigate whether the electro-acupuncture
      (EA) is beneficial to extenuate cerebral ischemic injuries following the middle
      cerebral artery occlusion (MCAO) in monkey. The results indicated that after
      MCAO. the EEG was severely inhibited, while the EEG recovery was slow after
      reperfusion compared with the control group. EA, given between the acupuncture
      points Baihui Point (GV. 20) and Renzhong Point (GV. 26) with a dense-sparse
      waveforms,which can be transformed into each other when dense or sparse wave is
      terminated, facilitated the recovery of EEG after ischema. The local cerebral
      blood flow (ICBF) in the striatum decreased during MCAO, whereas EA improved the
      ICBF significantly. The neurological deficit scale significantly decreased after
      ischemia but increased in EA group. The brain swelling coefficient (right/left)
      increased significantly in the ischemia group, but EA attenuated this increase.
      The neuropathological study showed that EA could significantly decrease the
      infarct area (p<0.05) and increase the percentages of the residual cells in the
      ipsilateral striatum and cortex (p<0.05 respectively). These results implied that
      EA is effective to extenuate cerebral ischemic injuries following the transient
      middle artery occlusion in monkeys.

PMID- 12044021
TI  - Bioterrorism and the Biological Weapons Convention--the wider context.

PMID- 12044022
TI  - The United Nations and the promotion of peace.
AB  - Despite the end of the cold war, many other conflicts persisted in the 1990s. The
      hope that a peace dividend would help to alleviate poverty was replaced by doubts
      regarding the effects of free market globalization and environmental constraints.
      Future concerns include the continuing aftermath of the cold war, the increased
      destructiveness of modern warfare, despite the increased sophistication of modern
      weaponry, the widening poverty gap between a wealthy elite and the majority of
      the world's population and developing global economic and environmental threats.
      The response to all this should be economic co-operation for sustainable
      development, including trade reform, and radical change in the environmental
      impact of the industrialized countries. Yet it appears that the response of the
      US, and to a lesser extent Europe, is to maintain the status quo in its own
      interests by military means, an attitude that seems to have been reinforced by
      the events of 11 September 2001. Nevertheless, these developments are opposed by
      citizen groups in the developed world and by analysts in the South. The United
      Nations and its agencies have been at the forefront of analysis and proposals for
      action in many of these fields. Its role is likely to increase in the next 30
      years and it must be made as effective a global body as possible.

PMID- 12044023
TI  - Biological warfare: the threat in historical perspective.
AB  - The story of work on biological warfare in the twentieth century is briefly
      reviewed and the history of the British programme analyzed, largely from
      documents now available in the Public Records Office. The position of the United
      Kingdom in relation to other military and political issues has varied, as has its
      overall attitude from time to time. In the 1930s a defensive stance was linked to
      the health effects of conventional war. During and after the Second World War the
      objective was to obtain a biological bomb before actual or potential enemies, but
      later the emphasis returned to a more defensive stance, with attempts to assess
      the hazard over wide areas. Any evaluation of the effects of new developments in
      genetics should take the changing nature of these past assessments into account.

PMID- 12044024
TI  - The potential for abuse of genetics in militarily significant biological weapons.
AB  - Concern has been expressed at successive Review Conferences of the Biological and
      Toxin Weapons Convention (BTWC) regarding the possible misuse of new biological
      knowledge; this article reviews some of these developments. Genetic manipulation,
      and genomics in particular, would modify existing pathogens and render previously
      harmless organisms pathogenic. Viruses could be modified as vectors to alter
      their pathogenicity in animals and man or act as carriers for genes or toxins.
      Plant pathogens, particularly fungi, could be modified as biological warfare
      agents against crops. An effective verification protocol for the BTWC is an
      essential part of the web of deterrence against these developments.

PMID- 12044026
TI  - Verification of the biological weapons convention: what is needed?
AB  - The lack of transparency and verification of the Biological Weapons Convention
      (BWC) is one factor behind the current weakening of the ban on biological
      weapons. Despite recent setbacks, governments need to fill the verification gap
      so that violations of the BWC can be detected and deterred. Continued talks on a
      strong verification mechanism for the BWC should aim for an open verification
      regime and one that is flexible enough to adapt to new technical and political
      circumstances. Effective monitoring of compliance with the BWC will require
      concerted effort by governments and civil society.

PMID- 12044025
TI  - Hope and ambition turn to dismay and neglect: the Biological and Toxin Weapons
      Convention in 2001.
AB  - The background to the failure of the December 2001 Fifth Review Conference of the
      Biological and Toxin Weapons Convention (BTWC) to agree a politically binding
      final declaration is discussed. Negotiations in the Ad Hoc Group (AHG) of the
      BTWC, which was set up after the 1994 Special Conference, are described.
      Accusations of non-compliance with the BTWC are not new and it is concluded that
      the ultimate failure of the 2001 Review Conference was principally, but not
      entirely, due to rejection by the United States that the AHG should remain in
      being. Strengthening the BTWC remains as important as ever, but it remains to be
      seen if there is the political will to achieve this.

PMID- 12044028
TI  - Landscape with dead sheep: what they did to Gruinard Island.
AB  - In the context of intensified international concern about biological weapons
      (BW), this article looks at the pioneering British research in this field during
      the Second World War, which caused the long-term contamination of Gruinard Island
      in north-west Scotland. Public Record Office documents have been examined to show
      how scientists reported on the experiments at the time and what they thought
      about their (top secret) work, as well as how politicians directed their efforts
      and used their results, leading to continued BW research post-war. In the 1960s
      the contamination became known and discussed in the media and was eventually the
      subject of a public announcement. Decontamination was not regarded as a practical
      proposition until the 1980s and was undertaken in 1986 in two areas of the
      island, which was declared safe in 1990. Some doubts remain locally about the
      extent and effectiveness of the clean-up process, along with a legacy of
      bitterness.

PMID- 12044027
TI  - Closing loopholes in the Biological Weapons Convention.
AB  - The Biological and Toxin Weapons Convention (BTWC) received two major blows in
      the past months. Negotiations for a protocol to strengthen the BTWC came to a
      halt and the Fifth Review Conference was unable to reach agreement on a final
      declaration. In addition, ongoing research projects, predominantly in the United
      States, are threatening to undermine the comprehensive ban on the development,
      production and use of biological weapons. This article provides two examples of
      research that exploit perceived loopholes in the BTWC or impinge on the scope of
      the Convention, namely the planned use of biological agents for forced drug
      eradication and the development of anti-material agents.

PMID- 12044029
TI  - Abolishing 29 February.

PMID- 12044031
TI  - Therapeutic monoclonal antibodies: trends in development and approval in the US.
AB  - Monoclonal antibodies have significant potential as therapeutic agents because of
      their ability to bind to specific antigens. To determine trends in the clinical
      development and approval processes for therapeutic mAbs, data on 199 mAbs that
      entered clinical study from 1980 to 2001 were collected and analyzed. Of the 199
      mAbs, 75 are in clinical development, two are undergoing Food and Drug
      Administration (FDA) review, and 11 are FDA approved. Approval success rates for
      murine, chimeric and humanized mAbs, and clinical and approval phase lengths for
      mAbs, are presented. In addition, mAbs that are either in phase III, FDA-review,
      or are FDA approved for antineoplastic or immunological indications are
      described.

PMID- 12044030
TI  - The Trimera mouse: a system for generating human monoclonal antibodies and
      modeling human diseases.
AB  - A Trimera mouse is constructed through a three-step process. Firstly, a normal
      mouse host is rendered immuno-incompetent by a lethal split-dose total body
      irradiation. Secondly, the myeloid and erythroid lineages are reconstituted by
      transplantation of bone marrow cells from a genetically immune-deficient mouse
      donor. Thirdly. the resulting preconditioned mouse is transplanted with human
      cells or tissues that can be maintained in the foreign, yet supporting,
      environment for a considerable period of time. Immunization of Trimera mice,
      engrafted with human immune cells, induces a strong human immune response,
      thereby enabling generation of human therapeutic monoclonal antibodies (mAbs) via
      hybridoma technology. Transplantation of infected human tissue into the
      preconditioned mice results in the creation of Trimera mouse models for human
      diseases.

PMID- 12044032
TI  - DNAzymes: cutting a path to a new class of therapeutics.
AB  - DNAzymes are synthetic catalytic deoxyribonucleic acid molecules that can be
      engineered to bind to their complementary sequence in the target nucleic acid
      through Watson-Crick base pairing and cleave at predetermined phosphodiester
      linkages. This article reviews the recent use of DNAzymes as probes of molecular
      function and their potential applications in clinical medicine.

PMID- 12044033
TI  - Towards optimal design of second-generation immunomodulatory oligonucleotides.
AB  - The goal of using of oligodeoxyribonucleotides containing CpG dinucleotides (CpG
      DNA) as immunomodulatory agents has been realized in recent years. Therapeutic
      applications of CpG DNA as monotherapies and as adjuvants in combination with
      vaccines, antibodies, antigens and allergens for a number of disease indications
      are rapidly expanding, and the safety and efficacy of several first-generation
      CpG DNA agents are being evaluated in human clinical trials. The biological
      effects of CpG DNA have been known for two decades; however, only recently has a
      specific receptor(s) that recognizes CpG DNA and activates immune cascade been
      identified. A number of sequence and structural characteristics of CpG DNA and
      chemical modifications that influence immunostimulatory activity have been
      identified. In this article we summarize the recent progress in understanding the
      structural and chemical characteristics of CpG DNA that are significant for
      molecular recognition. In addition, we describe the design of second-generation
      CpG DNA agents, and clinical applications of first-generation agents.

PMID- 12044034
TI  - Selective inhibition of DNA methyltransferase enzymes as a novel strategy for
      cancer treatment.
AB  - A common event in the development of human neoplasia is the loss of growth
      regulatory tumor suppressor functions. Methylation of 5'-CpG islands of tumor
      suppressor genes and elevated levels of the DNA-(cytosine-5)-methyltransferase
      enzymes (DNMT1, 3A and 3B) are also prevalent features of human neoplasia.
      However, direct evidence that elevated DNMT enzyme levels alter gene expression
      and influence oncogenesis has been difficult to obtain due to the lack of
      specific DNMT inhibitors. We have developed potent and selective antisense
      inhibitors of the known DNA methyltransferases. MG-98, a second-generation DNMT1
      specific antisense inhibitor currently in phase II clinical trials, reactivates
      silenced tumor suppressor genes and inhibits the growth of cancer cells in vitro
      and in preclinical in vivo models. Here, we will review the discovery and
      development of MG-98 as a cancer therapeutic.

PMID- 12044035
TI  - Prostate cancer: status of current treatments and emerging antisense-based
      therapies.
AB  - Prostate cancer, like most other solid tumors, represents a heterogeneous entity
      consisting of a mixture of androgen-dependent and androgen-independent cells.
      Although proliferation of prostate tumor cells is often initially androgen
      dependent, the inevitable development of androgen-insensitivity in late-stage
      prostate cancer renders androgen-suppressing treatments ultimately ineffective.
      Non-hormonal chemotherapy induces apoptosis in actively proliferating cells and
      is typically of little value, since prostate cancer demonstrates very slow growth
      kinetics. Objective response rates of < 10% and no improved survival rates have
      been observed in several hundred clinical studies using both experimental and
      approved chemotherapeutic agents. An improved understanding of the molecular
      mechanisms responsible for the onset of the disease, as well as the factors that
      control the proliferation of prostate cancer cells, have identified key changes
      in gene expression during cancer progression, especially from androgen-dependent
      to androgen-independent status. Manipulation of the genes implicated in disease
      progression represent an important approach for therapeutic intervention. This
      review summarizes recent progress that has been made with the use of antisense
      technology with various chemistries to modify gene expression, a strategy that
      seems to hold great promise for prostate cancer therapy.

PMID- 12044036
TI  - The role of target accessibility for antisense inhibition.
AB  - It appears that the application of antisense nucleic acids to drug development
      and gene function analysis are now established fields, and success in the use of
      antisense molecules has increased over recent years through modulating chemical
      and biological properties of oligonucleotides via the specific chemistry employed
      in their construction. In contrast, the targets of antisense nucleic acids are
      unchangeable RNA molecules, each with a defined strcuture. The local properties
      of the target represent a major limitation of the effectiveness of complementary
      nucleic acid inhibitors, and as such the search for appropriate local target
      sites for the invasion of an antisense strand is the focus of current research.
      Here, recent developments in the study of target structures and their
      accessibility for antisense nucleic acids, as well as concepts for their
      analysis, will be summarized.

PMID- 12044038
TI  - Potential therapeutic applications of decoy oligonucleotides.
AB  - Recent progress in molecular biology has provided new techniques with which to
      inhibit target gene expression. In particular, the application of DNA
      technologies, such as antisense oligonucleotide (ODN) strategies to regulate the
      transcription of disease-related genes in vivo, have significant therapeutic
      potential. Recently, transfection of cis-element double-stranded oligonucleotides
      (decoy ODNs) has been reported as a new powerful tool in a new class of anti-gene
      strategies for gene therapy. Transfection of double-stranded ODN corresponding to
      the cis sequence will result in attenuation of the authentic cis-trans
      interaction, leading to removal of trans-factors from the endogenous cis-elements
      with subsequent modulation of gene expression.

PMID- 12044037
TI  - Allosterically controllable maxizymes for molecular gene therapy.
AB  - Ribozymes are small and versatile nucleic acids that can cleave RNAs at specific
      sites. These molecules have great potential to be used as effective gene
      therapeutic agents. However, conventional ribozymes have, in some cases, failed
      to exhibit precise cleavage specificity because they require cleavable sequences
      in the target mRNA. Recently, we demonstrated that an allosterically controllable
      novel ribozyme, designated the maxizyme, is a powerful tool for disruption of an
      abnormal chimeric RNA target (BCR-ABL (b2a2) mRNA) in cells and in mice.
      Furthermore, more than five custom-designed maxizymes have demonstrated these
      allosteric functions in vitro and in vivo. Thus, maxizyme technology is not
      limited to a specific case but may have broad general applicability in molecular
      biology and in molecular gene therapy.

PMID- 12044039
TI  - The 'biased' evolution of targeted gene repair.
AB  - Targeted gene repair is a powerful yet controversial technique invented to direct
      single-base changes in chromosomal genes. The reaction mechanism has only
      recently come to light, and parameters that confer a level of control on the
      frequency of repair are still being defined in model genetic systems. Regulatory
      factors, such as strand bias, vector length, and the phase of the cell cycle in
      which targeting events take place, are now appreciated. This knowledge will lead
      to development of this technique for everyday genomics applications and,
      hopefully, gene therapeutics.

PMID- 12044040
TI  - Antisense treatment of caliciviridae: an emerging disease agent of animals and
      humans.
AB  - The Earth's oceans are the primary reservoir for an emerging family of RNA
      viruses, the Caliciviridae, which can cause a spectrum of diseases in marine
      animals, wildlife, farm animals, pets and humans. Certain members of this family
      have unusually broad host ranges, and some are zoonotic (transmissible from
      animals to humans). The RNA virus replicative processes lack effective genetic
      repair mechanisms, and, therefore, virtually every calicivirus replicate is a
      mutant. Hence, traditional therapeutics dependent on specific nucleic acid
      sequences or protein epitopes lack the required diversity of sequence or
      conformational specificity that would be required to reliably detect, prevent or
      treat infections from these mutant clusters (quasi-species) of RNA viruses,
      including the Caliciviridae. Antisense technology using phosphorodiamidate
      morpholino oligomers shows promise in overcoming these current diagnostic and
      therapeutic problems inherent with newly emerging viral diseases.

PMID- 12044041
TI  - Technology evaluation: adalimumab, Abbott laboratories.
AB  - Adalimumab (D2E7), a human monoclonal antibody that binds to and neutralizes
      TNFa, is being developed by Abbott (formerly Knoll), under license from Cambridge
      Antibody Technology (CAT), for the potential treatment of inflammatory disorders
      such as rheumatoid arthritis (RA) and Crohn's disease. It is also being
      investigated for the potential treatment of coronary heart disease. Phase II
      studies for Crohn's disease and phase III for RA were ongoing throughout 2001.
      Limited data are only available for RA. In January 2002, it was reported that
      phase III trials of adalimumab for RA had been completed, but details have not
      been published in the primary literature so far. At this time CAT and Abbott
      expected to file for US approval in the second quarter of 2002 with a launch date
      anticipated for 2003. Phase III data are expected to be presented at the European
      League Against Rheumatism meeting in June 2002. In November 2000, Lehman Brothers
      predicted a US launch in June 2002 with peak US sales of $600 million in 2007 and
      a launch in non-US markets in 2003 with peak sales in these markets of $300
      million in 2008. In December 2000, Merrill Lynch predicted regulatory clearance
      in the second half of 2003. The probability of adalimumab reaching the market is
      estimated to be 70%. In December 2000, Merrill Lynch predicted a 2003 launch,
      with estimated sales of pounds sterling 3.65 million in that year rising to
      pounds sterling 30.14 million in 2010. In March 2001, ABN AMRO predicted sales of
      $73 million in 2003 rising to $392 million in 2007.

PMID- 12044042
TI  - Simultaneous staining of cytoplasmic iron and collagen matrix in human liver
      biopsy specimens.
AB  - One of the major liver fibrogenic activators is the cellular iron overload that
      can severely damage parenchymal and non-parenchymal cells. The aim of this study
      was to investigate a histochemical staining technique that allows the
      simultaneous detection of the irregular deposition of matrix collagen and both
      the amount and distribution of iron in liver cells on the same histological
      section. The method was evaluated using 3-microm histological sections obtained
      from ten standard liver biopsy specimens taken from patients with hepatitis C
      virus-related diseases and simultaneous liver cell iron overload. The results
      indicate that the double-staining technique is simple, sensitive and rapid, and
      can be routinely applied to liver biopsy specimens for diagnostic purposes.
      Furthermore, it may also facilitate the study of the complex relationship between
      hepatic fibrosis and iron overload during common genetic or secondary liver
      metabolic disorders.

PMID- 12044045
TI  - Morpho-functional changes in human tendon tissue.
AB  - Insertion tissue biopsies of right arm common extensor tendons from 11 patients
      with chronic lateral epicondylitis were processed for light and electron
      microscopy. The subjects were aged between 38 and 54 years (only one was 25). The
      specimens showed a variety of structural changes such as biochemical and spatial
      alteration of collagen, hyaline degeneration, loss of tenocytes, fibrocartilage
      metaplasia, calcifying processes, neovascularization and vessel wall
      modifications. Tissue alterations were evident in limited zones of the tendon
      fibrocartilage in which the surgical resection was generally visible. The areas
      where the degenerative processes were localized, were restricted and in spatial
      contiguity with morphologically normal ones. The observed cases presented
      histological and electron microscopic findings that characterize lateral
      epicondylitis as a degenerative phenomenon involving all tendon components.

PMID- 12044043
TI  - CD69 expression on alpha-gliadin-specific T cells in coeliac disease.
AB  - Coeliac disease (CD) is a T-cell mediated immunological disease of the small
      intestine which is triggered in susceptible individuals by ingestion of gluten.
      The pathogenic mechanism of coeliac disease, and the role that alpha-gliadin
      specific T cells play in mucosal lesions and their involvement in peripheral
      blood is not yet explained at all. Previous studies have reported proliferative
      response to alpha-gliadin measured with the classic assay of 3HTdR incorporation.
      We analysed the activation antigen CD69 on T cells from CD patients and normal
      individuals following stimulation with alpha-gliadin and different antigens
      (tetanus toxoid, peptides unrelated to gliadin and PHA). CD69 coexpression with T
      cell CD3+ and proliferation marker Ki67 was evaluated with time. CD69
      coexpression with T cell CD3+, CD4+ and CD8+ was also evaluated. It was found
      that peripheral blood mononuclear cells (PBMC) of coeliac patients increased
      their percentage of CD69 positive T cells when stimulated with alpha-gliadin, in
      comparison with cells from controls. Significant T cell activation was found only
      in subjects not treated with the gluten free diet; a positive response was found
      also in two coeliac patients with selective IgA deficiency, anti-endomisium
      negative, without circulating IgA anti alpha-gliadin or anti-tissue
      transglutaminase antibodies. The CD69 expression after stimulation was compared
      with the standard method of 3HTdR incorporation. Our data show that CD69
      expression is useful to asses a specific T cell response to alpha-gliadin in
      coeliac disease. in a very short time. Moreover, the method allows to investigate
      T cell response at the lymphocyte subsets level, which represents a useful tool
      in the diagnosis of coeliac disease.

PMID- 12044044
TI  - Hydrophobins in ectomycorrhizas: heterologous transcription of the Pisolithus
      HydPt-1 gene in yeast and Hebeloma cylindrosporum.
AB  - Hydrophobins are fungal cell wall proteins involved in aggregation of hyphae.
      Upon the development of the ectomycorrhizal symbiosis between tree roots and
      fungal hyphae, the transcripts of hydrophobin genes markedly accumulated. As the
      precise role of these proteins in symbiosis is not yet known, we develop
      heterologous expression system of the Pisolithus hydrophobin HYDPt-1. This gene
      has been introduced in Saccharomyces cerevisiae and in the ectomycorrhizal
      basidiomycete Hebeloma cylindrosporum. Introns were required for hydPt-1
      transcript accumulation in the basidiomycete H. cylindrosporum. Heterologous
      transcript accumulation did not alter the phenotype of either species. The lack
      of altered phenotype resulted from the absence of HYDPt-1 polypeptide
      accumulation in transformed strains.

PMID- 12044046
TI  - Cytochemical localization and quantification of plasma membrane Ca2+-ATPase
      activity in mollusc digestive gland cells.
AB  - A cytochemical method allowing the localization and quantification of plasma
      membrane Ca2+-ATPase (PMCA) in frozen sections obtained from digestive gland
      cells of Mytilus galloprovincialis, Tapes tapes and Chamelea gallina, is
      presented. The method utilizes lead as a trapping agent of PO4(2-) ions released
      by Ca2+-ATPase activity. The amount of lead sulphide precipitate proportionally
      related to PMCA activity was quantified by a light microscopy digital imaging
      analysis system. The optimal assay conditions of Ca2+-ATPase activity evaluated
      at pH 7.4 were: 200 microM free Ca2+, 200 mM KCl, 2 mM ATP, and under such
      analysis conditions the enzyme showed a linear trend up to 60 min (at 20 degrees
      C). The PMCA activity was substrate specific: ADP was utilized only at a low rate
      (24% with respect to an equimolar ATP concentration), while glucose-6-phosphate
      and beta-glycerophosphate were poorly hydrolyzed. The enzyme activity was
      strongly inhibited by sodium ortho-vanadate. Our detection of a Ca2-ATPase
      activity at nanomolar concentrations of free Ca2+ suggests that we have
      identified a plasma membrane Ca2-ATPase involved in Ca2+ homeostasis. The Ca2+
      ATPase was found to be localized in the basal part of the plasma membrane in the
      digestive gland cells of Mytilus galloprovincialis and Tapes tapes, but in the
      apical plasma membrane of Chamelea gallina. The possible implications of the
      different cellular distributions of PMCA activity is discussed.

PMID- 12044047
TI  - Glycosidases during chick embryo lung development and their colocalization with
      proteoglycans and growth factors.
AB  - During development, the epithelial component of the lung goes through a complex
      orderly process of branching, following strict patterns of space and time.
      Proteoglycans, glycosaminoglycans and growth factors are fundamental components
      of the extracellular matrix and perform a key role in differentiative processes.
      The embryonic chick lung shows a specific glycosaminoglycan composition at
      different levels of branching and at different embryonic stages. Proteoglycan and
      glycosaminoglycan accumulation is the result of secretion, absorption and
      degradation processes. In this pathway, enzymes, such as glycosidases, growth
      factors and cytokines are involved. We examined the behaviour of glycosidases,
      such as beta-hexosaminidases (beta-N-acetyl-D-glucosaminidase, beta-N-acetyl-D
      galactosaminidase), beta-glucuronidase and beta-galactosidase, during the
      development of the lung bud. Our data show that the activity of the enzymes is
      closely linked to the processes of epithelial proliferation, bronchial tubule
      lengthening and infiltration of the surrounding mesenchyme. The
      glycosaminoglycans colocalize with transforming growth factor beta2 and
      interleukin-1 in the basement membrane and in the mesenchymal areas where the
      epithelium grows, and are complementary to the presence of the glycosidases. In
      conclusion, the activity of these glycosidases is spatially and temporally
      programmed and favors the release of the factors and the events which they
      influence.

PMID- 12044048
TI  - Apoptosis during chick inner ear development: some observations by TEM and TUNEL
      techniques.
AB  - In order to clarify the occurrence, distribution and possible role of apoptosis
      during inner ear development, the ultrastructural aspects (by TEM) (at 9-19
      incubation day and 1 day after hatching) and the distribution of the apoptotic
      phenomenon (by the TdT-mediated dUTP nick end-labeling technique), were studied
      in the crista ampullaris of chick embryo at 5-19 days of incubation to hatching
      and of postnatal 1-day old chick. We found, in the sensorial epithelium, dark
      supporting cells in chick embryos and mainly dark hair cells in postnatal chicks,
      both with ultrastructural features consistent with those of apoptosis. The
      presence of apoptotic phenomena was confirmed by the TUNEL technique. According
      to our findings, it is hypothesized that apoptosis in the inner ear may be
      involved: 1) at first, in macroscopic remodelling of the membranous labyrinth in
      early developmental stages, 2) later, in the correct differentiation of the hair
      and of the supporting cells, leading to characteristic cellular pattern formation
      and 3) finally, in physiological cell turnover of the postnatal chicken sensorial
      epithelium of the crista.

PMID- 12044049
TI  - Synchronized onset of nuclear and cell surface modifications in U937 cells during
      apoptosis.
AB  - In this study we investigated the relationship between nuclear and cell surface
      modifications (i.e. blebbing, phosphatidylserine [PS] and sugar residues
      exposure) in a monocytic cell line, U937, during apoptosis induced by oxidative
      stress (1 mM H2O2) or inhibition of protein synthesis (10 microg/ml puromycin).
      Dying cells were simultaneously observed for nuclear modifications, presence of
      superficial blebs and plasma membrane alterations. Morphological analysis
      performed by conventional fluorescence microscopy, or by transmission and
      scanning electron microscopy showed that the courses of nuclear and membrane
      alterations occured concomitantly, but the phenotype was dependent on the stage
      of the apoptotic process and the type of apoptogenic inducer used. The
      progression of apoptosis in U937 cells beyond early stages resulted in the
      extensive formation of blebs which concomitantly lost some typical markers of
      apoptosis, such as PS and sugar residues. Therefore, the modality by which the
      nucleus condenses, or the amount and the pattern of distribution of PS on the
      cell surface were, for each cell line, strictly related to the apoptogenic
      inducer. The morphological data reported in the present paper should lead to a
      more precise quantification of apoptosis by improving the detection of apoptotic
      cells in vivo (i.e. in tissue, organs), which is a crucial point in the
      evaluation of efficiency of antiproliferative drugs, such as antiblastic or
      immunosuppressive compounds.

PMID- 12044050
TI  - Spermiogenesis in the vermetid gastropod Dendropoma petraeum (Gastropoda,
      Prosobranchia).
AB  - The structure and maturation of the male gonad of the Mediterranean vermetid
      gastropod Dendropoma petraeum are described. Histological sections of the gonads
      were made throughout development and gonad activity was monitored at regular
      monthly intervals. During the autumn months the gonad is very small and is
      surrounded by a large quantity of connective tissue; it becomes more voluminous
      from December to August, with the highest growth peak in springtime. The stages
      of spermatogenesis were also observed and described.

PMID- 12044051
TI  - Histological and histochemical study of female germ cell development in the dusky
      grouper Epinephelus marginatus (Lowe, 1834).
AB  - The developmental stages of female germ cells were analysed in a wild population
      of the protogynous teleost Epinephelus marginatus (Lowe, 1834). 321 wild dusky
      grouper females were collected in the South Mediterranean Sea during the spawning
      season and their ovaries analysed using histological and histochemical
      techniques. Oocyte morphology, nucleus-cytoplasm ratio (N/C) range, location and
      movements of cytoplasmic inclusions during primary growth, vitellogenesis and
      final oocyte maturation were described. The distribution of proteins, lipids and
      carbohydrates through oocyte development was also investigated in 50 females.
      Lipid vesicles appeared firstly in the mid ooplasm of oocytes larger than 130
      microm, at the beginning of the secondary growth phase. Immediately afterwards,
      small carbohydrate granules (PAS and Alcian blue positive) appeared before the
      occurrence of the first yolk granules. Tyrosine-enriched proteins were especially
      evidenced in the zona radiata interna of late vitellogenic oocytes. Specific
      lectin binding patterns reflected characteristic differences in the content and
      distribution of specific sugar moieties expressed in the oocytes during
      vitellogenesis and final maturation. At the end of vitellogenesis and during
      final maturation, follicular cells, zona radiata, and cortical alveoli were
      characterised by a strong increase of specific binding for WGA.

PMID- 12044052
TI  - Genetic susceptibility to malignant diseases--ethical issues. Minireview.
AB  - Ethical problems connected with genetic testing with the intention of the
      measurement of the susceptibility or predisposition to malignant tumors are
      presented (respect for autonomy, beneficence, nonmaleficence, confidentiality,
      privacy, veracity and truth-telling, informed consent, right to know, right not
      to know, informational self-determination, etc.). Various aspects dealing with
      ethics of screening and research projects involving human subjects are discussed
      as well.

PMID- 12044054
TI  - The immunohistochemical and serological determination of p53 protein in patients
      with malignant lymphomas.
AB  - The product of mutated p53 gene is a protein with abnormal conformation, impaired
      DNA binding, and a prolonged half life, the latter of which results in
      immunohistochemically detectable levels within nuclei of malignant cells. The
      present study was aimed at the immunohistochemical determination of p53
      overexpression in patients with various histological types of nonHodgkin's
      lymphomas (NHL), with a particular interest in gastric lymphomas. In these
      patients, as well as in controls, also serological determinations of p53 protein
      were performed using an ELISA method. Immunohistochemical overexpression of p53
      protein was found in 21% of NHL patients, with the highest incidence of p53
      immunoreactivity in cases of Burkitt's lymphoma, follicle center lymphoma grade
      III, and diffuse large B-cell lymphoma. In gastric lymphomas the overall
      incidence of p53 immunoreactivity was as high as 46%. Serological ELISA
      determinations of p53 protein in NHL patients and in controls remained below the
      lowest detection limit of the method in all 128 cases. Considering that p53
      mutations are associated with poor response to therapy, and consequently with
      poor prognosis, it is of great importance to determine the subset of patients
      that are particularly at risk for an unfavorable outcome and should be treated
      more aggressively. Immunohistochemical determinations of p53 overexpression
      represent a rapid and simple, yet somewhat imperfect technique for an estimation
      of the frequency of mutational events. On the other hand, serological
      determinations of p53 protein are completely inadequate for the evaluation of p53
      status.

PMID- 12044053
TI  - Activity of some lysosomal enzymes in serum and in tumors of patients with
      squamous cell lung carcinoma.
AB  - The aim of the study was an assessment of some lysosomal enzymes activity in
      serum and in tumors of patients with lung cancer histopathologically confirmed as
      squamous cell lung carcinoma. The first group constisted of 10 patients with
      stage II of the disease and the second group consisted of 11 patients with stage
      III of the disease. Lysosomal enzymes activities were assayed in serum before
      surgery and on the 10th day after surgery in serum and in tumors. Arylsuphatase,
      cathepsin D and acid phosphatase activities were higher in the patients serum
      than in that of the control group. The decrease of arylsulphatase and cathepsin D
      activities after surgery was statistically significant in both groups of
      patients, but the cathepsin D activity was still 3 times higher in patients than
      in those from the control group. The decrease of acid phosphatase activity after
      surgery was about 50% in both groups of patients and this decrease was
      statistically significant. The arylsulphatase and acid phosphatase activity in
      tumors was nearly 3 times higher in stage III patients than it was in stage II
      patients, but the cathepsin D activity was nearly the same in both patient
      groups. Higher lysosomal enzyme activity may be a useful factor in diagnosing and
      monitoring of lung cancer. However, further investigations are needed.

PMID- 12044055
TI  - Switching (overtargeting) of estrogen effects and its potential role in hormonal
      carcinogenesis.
AB  - Peculiarities of the estrogens influence on target tissues is one of the crucial
      problems in understanding of the estrogen-induced carcinogenesis and
      anticarcinogenesis mechanisms. Conditions or factors enhancing the genotoxic
      component in total effect of estrogens (on the uterine tissue, in particular) are
      very important, since these factors may influence both the hormonal
      carcinogenesis type and biological properties of the developing hormone-dependent
      tumors. In this study female rats (3 months of age at the beginning of
      experiment) have been given plain water (group 1) or 5% ethanol solution over 4
      months. Rats which received ethanol were further divided into 6 groups (groups 2
      7). During last 2 months of the experiment N-acetylcysteine was given to rats in
      group 3, ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E)--to group 4,
      melatonin--to group 5, carnosine--to group 6; the rats in group 7 swam for 5 days
      a week according to the so called developing schedule. 2.5 weeks before the end
      of experiment all rats underwent bilateral ovariectomy, and over 11 days
      preceding the last day of the experiment they received injections of estradiol (2
      microg intramuscularly daily). When the experiment was over, estradiol and
      cholesterol blood levels, progesterone receptors content, peroxidase activity,
      proliferation index, percent of cells in S and G2/M phases, thickness of
      endometrium and rate of DNA damage in uterine tissue (COMET assay) and estradiol
      2-hydroxylase activity in liver tissue were measured. The conclusion was that
      administration of 5% ethanol combined with estrogen injections results in
      genotoxic (G) changes in the uterus, which may be prevented by giving N
      acetylcysteine or melatonin. Combination of vitamins C and E enhances some
      features of hormonal (H) estrogen effects (uterine weight, induction of
      progesterone receptors), but attenuates the other (proliferation index).
      Consequently, the combination of N-acetylcysteine and optimal doses of ascorbic
      acid and alpha-tocopherol may be recommended for prevention of the phenomenon of
      switching of estrogen effects [PSEE] (e.g. enhancement of G-component and
      decrease of H-component), observed particularly in cases of the treatment with
      tobacco smoke or ethanol consumption in more than moderate (15%) concentrations,
      which lead to the increased risk of genotoxic type of hormonal carcinogenesis.

PMID- 12044057
TI  - Determination of optimal conditions for detection of acute myeloid leukemia
      t(8;21) and t(15;17) translocations using RT-PCR.
AB  - Prognosis of patients with acute myeloid leukemia (AML) is not satisfactory. Long
      time remission can be achieved only in 25-40% children with AML. The aim of the
      study is to improve diagnosis of AML in cases characterized by specific
      chromosomal translocations t(8;21) and t(15;17). These translocations can be
      efficiently detected using reverse transcriptase-polymerase chain reaction (RT
      PCR). To determine optimal conditions for detection of the t(8;21) and t(15;17)
      translocations in human cells, we performed a detail study of experimental
      conditions for RT-PCR on human cell lines NB-4 and KASUMI-1. For detection of
      t(8;21) using Pfx polymerase, the optimal PCR conditions included magnesium ion
      concentration in the range of 0.6 to 1 mM, 0.4 microM primer concentration, 5
      degrees C annealing temperature and 1 microl of template cDNA. For detection of
      t(15;17) using the Pfx polymerase, the optimal conditions included 1 mM magnesium
      ion concentration, 0.6 microM primer concentration, 63 degrees C-66 degrees C
      annealing temperature and 2 microl of template cDNA. The results proved to be
      valid for clinical diagnostics of these chromosomal aberrations in blood and/or
      bone marrow samples of AML patients.

PMID- 12044056
TI  - Cytotoxic T lymphocyte precursor frequency analysis in the selection of HLA
      matched unrelated donors for hematopoietic stem cell transplantation: the
      correlation of CTLp frequency with HLA class I genotyping and aGVHD development.
AB  - The selection of human leukocyte antigen (HLA) compatible unrelated donors for
      hematopoietic stem cell transplantation (HSCT) is based on the direct genotyping
      of HLA class I and class II alleles (HLA-A, -B, -C, -DRB1, -DQB1 loci). The
      cellular test estimating the frequency of cytotoxic T lymphocyte precursors
      (CTLp) has been included into the selection procedure of unrelated donors to
      detect the class I alloreactivity and to predict acute graft versus host disease
      (aGVHD) occurrence and severity. The relationship between HLA-A, -B, -C
      high/medium resolution genotyping and CTLp activation was analysed in the cohort
      of 78 unrelated donor/patient pairs indicated for HSCT. The high frequency of
      CTLp (> 1:100,000) correlated significantly (p < or = 0.0002) with the
      incompatibilities in alleles of HLA-A, -B, -C loci. Nevertheless, the results of
      HLA-A, -B, -C genotyping and CTLp assay are not fully alternative, suggesting
      that the CTLp test gives its specific information. The high CTLp frequency
      (CTLpf) in 14/35 pairs fully matched by HLA class-I alleles genotyping could
      reflect the influence of another factors upon the CTLp activation. On the
      contrary, the low CTLp frequency values (< or = 1:100,000) found in 8/43 pairs
      with existing HLA class-I alleles incompatibilities could indicate the
      immunological permissivity of these particular mismatches. The clinical relevance
      of the CTLp test for aGVHD prediction has been also analysed. The relationship
      between CTLp activation in vitro and the incidence and severity of aGVHD was
      evaluated in 37 patients who underwent allogeneic HSCT. The severe form of aGVHD
      (grade III-IV) developed in 9 of 18 cases (50%) with the high pretransplant CTLpf
      value. The patients with the low CTLpf (n = 19) suffered from the severe form of
      aGVHD in 2 cases (10%) only, the remaining 17 patients from this group were
      without aGVHD symptoms or developed only the mild form of aGVHD (I-II). The
      relationship between CTLp results and the incidence and severity of aGVHD was
      found statistically significant (p < or = 0.01).

PMID- 12044058
TI  - Acetaminophen modulations of chemotherapy efficacy in MDAH 2774 human
      endometrioid ovarian cancer cells in vitro.
AB  - Epidemiological data have correlated consumption of nonsteroidal antinflammatory
      drugs with lowered risk for many types of cancer, and some recent studies
      indicate a reverse correlation with acetaminophen consumption and ovarian
      malignancy. In this study we examined effects of acetaminophen on plating, S
      phase and colony growth of MDAH 2774 human endometrioid ovarian carcinoma, as
      well as sensitivity of this cell line to carboplatin in all three tests, and
      paclitaxel to clonogenic assay. Acetaminophen significantly enhanced S-phase in
      first 72 hours and enhanced cell population in 96 hours of plating
      monitorization, but decreased one week colony growth by approximately 80%, which
      was in the range of cytotoxic drugs. Interestingly with low dose carboplatin in
      first 72 hours acetaminophen enhanced cell proliferation more profoundly, but
      only thereafter decreased cell growth synergistically with carboplatin. It did
      not effect paclitaxel colony growth inhibiting acitivity. MDAH-2774 cell line
      lack p-53 and MSH-2, which are both 'gatekeeper' apoptosis inducing genes against
      genome damaging insult. Thus, presence of lower doses of oxidizing drugs may help
      the induction of proliferative signals, but only their sustained presence may
      overcome such signals and ultimately bring to cell demise.

PMID- 12044060
TI  - Bilateral breast cancer.
AB  - The aim of this study was to evaluate the clinical and pathological features of
      breast cancer patients with bilateral breast cancer and to assess the impact of
      the second breast cancer on their prognosis. Thirty six breast cancer patients
      with bilateral (metasynchronous) cancer were treated in Greatpoland Cancer Center
      from 1983 to 1995. It constituted 4.1% of all breast cancer patients treated in
      those years. 5-year survival rates were compared with clinical data (age,
      clinical stage, histological diagnosis), methods of treatment and length of
      interval between occurring of both tumors. Five year survival of patients treated
      for second breast cancer was 55.6% (20/36), disease-free survived--15/36 (41.7%).
      5-year survival rate was greater in group of patients with clinical stage T1 or
      T2 (69.6%, 16/23) than in group with T3 or T4 (30.8%, 4/13) (p=0.009). In group
      of 20 patients without nodal involvement (N0) 5 years survived 75.0% of patients
      (15/20), in group with N1--11.1% (1/9) (p=0.01). Length of interval between both
      breast tumors influenced 5-year survival rate. In group of patients with interval
      longer than 5 years, 5-year survival rate was 73.9% (17/23), in group of patients
      with interval shorter than 2 years--0% (0/6) (p=0.002). No correlations were
      observed between survival rate and age, histological diagnosis, methods of
      treatment.

PMID- 12044059
TI  - Chemoembolization for liver metastases from colorectal carcinoma: risk or a
      benefit.
AB  - Results from clinical trials do not allow definitive conclusions about the role
      of chemoembolization (ChE) in the treatment of colorectal cancer (CRC) liver
      metastases. The aim of present phase II study was to investigate toxicity and
      efficacy of ChE for patients, with unresectable colorectal liver metastases after
      failure of 5-FU based chemotherapy. Secondary endpoint was clinical benefit
      measurement. Eleven patients were enrolled in first stage (two-stage Simon
      design), 2 males/9 females, median age 60 (46-71). Performance status was I in 8
      patients and II in 3 patients. All patients had radical surgery, 7 of them
      adjuvant chemotherapy and 4 systemic chemotherapy. The ChE regimen consisted of
      an injection of iodinated oil Lipiodol with mitomycin C (3 mg/ml). Repeated
      treatments were performed at 9- to 12-week intervals. We applied 17 ChE (median
      1/pts.). Clinical benefit was a composite of measurements of pain, ECOG
      performance status, weight and tumor fever. Study was stopped after first stage
      because non of the patients (pts) achieved objective response (RECIST). Stable
      disease occurred in 5 pts (45%). Median time to progression was 3 months (range 3
      9 months). Median survival was 9 months (range 4-16 months). A decrease of the
      baseline carcinoembryonic antigen level occurred in 0% of the cases. Clinical
      benefit was recorded in one patient. Common toxicity included a "postembolization
      syndrome," which consisted of fever, pain in the right upper quadrant, nausea,
      and vomiting. Grades 3-4 toxicity (NCI-CTC) followed transaminases 6/11, LDH
      4/11. In addition, a drop in F V levels was noted in 5 pts, F VII in 9, F IX in 2
      and F X in 10 pts. Decrease in At III levels occurred in 6 pts and FDP appeared
      in one. Thus, The ChE as performed in the present study did not appear to bring
      any benefit; furthermore, significant liver toxicity compromises the safety of
      such procedure.

PMID- 12044061
TI  - A cytochemical note on nucleoli of granulocytic precursors and granulocytes in
      patients suffering from the refractory anemia with excess blasts (RAEB) of the
      myelodysplastic syndrome (MDS).
AB  - Nucleoli were studied in the proliferation as well as maturation granulopoietic
      compartment in patients suffering from refractory anemia with excess blasts
      (RAEB) of the myelodysplastic syndrome (MDS) by means of simple cytochemical
      procedures for the demonstration of nucleolar RNA and silver stained proteins of
      nucleolus organizer regions. Regardless of the procedure used for the nucleolar
      visualization, early stages of the granulopoietic compartment and particularly
      myeloblasts of RAEB patients were characterized by reduction of the nucleolar
      number expressed by the nucleolar coefficient the values of which resembled those
      described previously in acute myeloid leukemias. The reduced values of the
      nucleolar coefficient of these cells in silver stained specimens of RAEB patients
      were accompanied by a decreased number of clusters of silver stained particles
      representing interphasic silver stained nucleolus organizer regions (AgNORs). The
      reduction of these clusters was also described previously in leukemic cells. In
      addition, the differences in the values of the nucleolar coefficient of
      granulocytic precursors between specimens stained for RNA and those stained with
      the silver reaction might reflect changing composition and proportions of
      nucleolar components in the course of the granulocytic development.

PMID- 12044062
TI  - Characteristics of nasal T/NK-cell lymphoma among Brazilians.
AB  - Nasal T/NK-cell lymphomas are highly associated with Epstein-Barr virus (EBV).
      They are more frequent in Asia than in Western countries. In Central and South
      America there are few studies about nasal T/NK-cell lymphoma and they have shown
      a strong predominance of this phenotype in Native American descents, supporting
      the hypothesis of a racial predisposition for the disease. We studied the
      lymphomas involving midline facial region at a Brazilian institution. T/NK cell
      lymphomas (16/25) were more frequently found compared to B lymphomas (9 cases,
      all B large cell). T/NK cell lymphomas involved predominantly the nasal region.
      Histologically they showed angioinvasion and necrosis. All of them were positive
      for CD3 and CD56 and showed numerous tumor cells labeled by EBER-1. Although
      disease was localized in 61% at diagnosis, there was no tendency to cure. The
      racial distribution of patients with T/NK-cell phenotype was similar to that
      found in B-cell lymphomas. EBV was more frequently found in adenoids than in
      palatine tonsils. In inflammatory lesions of the nasal and palatal regions EBV
      was not found. In the present study the relative frequency of T/NK versus B cell
      sinonasal lymphomas was high and similar to that observed in other Latin American
      countries. However, there was not any racial association with T/NK-cell phenotype
      and the tumor showed an agressive behavior similar to that reported in Asia. The
      high frequency of EBV-positive lymphocytes in nasopharyngeal lymphoid tissue
      (adenoids) suggests that they could serve as a reservoir for the virus.

PMID- 12044063
TI  - Tamoxifen therapy and hepatic steatosis.
AB  - Tamoxifen has been used for a long time as a hormonal treatment in breast cancer.
      Recent studies in pre and postmenopausal women have shown that tamoxifen exhibits
      favorable effects on the lipid profile. In this study we investigated the effects
      of tamoxifen on lipid profile and hepatic steatosis. Fifty two (31 postmenopausal
      and 21 premenopausal) women with breast cancer treated with tamoxifen at a dose
      of 20 mg daily were included in the study. Serum lipid parameters (total
      cholesterol, high and low density lipoprotein cholesterol and triglyceride) were
      measured baseline and at the 6th month of tamoxifen treatment. Upper abdominal
      ultrasonography was performed before and at the 6th month of therapy for
      assessment of liver steatosis. We obtained decreased levels of serum total
      cholesterol after 6 months of tamoxifen treatment (p < 0.05). However, we did not
      detect any changes in triglyceride and high-density lipoprotein cholesterol
      levels (p > 0.05). Increased liver steatosis was observed in 22 patients (42.3%)
      after tamoxifen treatment. We could not detect increase in lipid levels in these
      patients. There was no significant difference between the lipid levels in the
      patients with increased liver steatosis and stable or no liver steatosis. Whether
      hepatic steatosis is dependent on lipid changes in tamoxifen use should be
      further investigated.

PMID- 12044064
TI  - Inhibition of carcinogenic and clastogenic effects of N-nitrosomorpholine in rats
      immunized with tularemia vaccine.
AB  - The aim of the present work was to study whether immunization of rats with
      tularemia live vaccine (TLV) can influence carcinogenic and mutagenic action of N
      nitrosomorpholine (NNM). The experiments were performed with male albino random
      bred rats. The first group of rats was immunized with TLV 15 days before the
      start of experiment. These animals and the second group (positive control) were
      treated with NNM orally, (total dose was about 250 mg/rat). Rats including
      solvent (negative) control group were killed 12 months after the start of NNM
      treatment to study the carcinogenic effect. Experiments to study the influence of
      TLV on mutagenesis were performed with three groups of rats: the first (on 15th
      day after immunization with TLV) and the second group were injected
      intraperitoneally with NNM 100 mg/kg b.w. on 2 consecutive days, third group
      received only distilled water. The results of long-term experiment have shown
      that tumor incidence (both malignant and benign) in rats of positive control
      group was 74.2%. Immunized rats had significantly decreased incidence of tumors
      compared with the previous group--36.1%. Micronuclei level in bone marrow cells
      of non-immunized rats was statistically significantly higher than that in
      immunized rats. The inhibition of carcinogenic and clastogenic effects of NNM in
      rats immunized with TLV are probably due to a decrease in cytochrome P-450
      activity. We suggest that immunization of rats with TLV can protect them against
      the cacinogenic and clastogenic actions of some chemicals.

PMID- 12044065
TI  - The essential role of hydrodynamic shear force in the formation of biofilm and
      granular sludge.
AB  - Biofilm and granular sludge processes are promising biotechnology for wastewater
      treatment. The formation, structure and metabolism of immobilized microbial
      community are associated very closely with hydrodynamic shear force in reactors.
      Therefore, this paper attempts to review the essential role of shear force in the
      formation and performance of biofilm and granular sludge. More compact, stable
      and denser biofilms, aerobic and anaerobic granules form at relatively higher
      hydrodynamic shear force. It is clearly shown that shear force has significant
      influences on the structure, mass transfer, production of exopolysaccharides,
      metabolic/genetic behaviours of biofilms, aerobic and anaerobic granules. In an
      engineering sense, hydrodynamic shear force can be manipulated, as a control
      parameter, to enhance microbial granulation process. It can be concluded that the
      knowledge regarding the effects of hydrodynamic shear force on biofilms and
      granules is far from complete and much research is still needed to fully
      understand the relevant mechanisms. Some of these future research niches are
      therefore outlined.

PMID- 12044066
TI  - Cadmium induced adaptive responses of certain biogeochemical cycling bacteria in
      an aquatic system.
AB  - The population growth of some biogeochemical cycling bacteria (heterotrophic
      bacteria (HB), ammonifying bacteria (AB), ammonia oxidizing bacteria (AOB),
      denitrifying bacteria (DNB) and cellulose decomposing bacteria (CDB)), as well as
      ammonification, and denitrification rates were determined in simulated pond
      systems treated with full doses (FDs) and split doses (SDs) of cadmium.
      Reductions in bacterial density and nitrogen activity rates were more severe for
      the FD and SD followed by a slight recovery in both. Among the test groups,
      reductions were maximal in the AOB and DNB and lowest for the CDB populations,
      suggesting that the latter had greater potential for cadmium resistance.
      Bicarbonate alkalinity of water was found to exert a profound influence in
      counteracting cadmium stress in the system, as strong negative correlations
      between this parameter and bacterial mass were evident in the SD treatment.
      Though the aquatic microbial populations were greatly altered by cadmium stress,
      the normal operating range of the system was restored at a later time with the
      CDB population showing higher degree of adaptive responses.

PMID- 12044067
TI  - Organic colloid separation in contrasting aquatic environments with tangential
      flow filtration.
AB  - The use of tangential flow filtration (TFF) for size fractionation of natural
      dissolved organic matter was investigated. The performance of regenerated
      cellulose membrane with a nominal molecular weight cut-off of 1 kDa was examined
      on 20 samples from lake, river and estuary systems, characterised by contrasting
      dissolved organic carbon (DOC) contents and conductivity. The evaluation was
      based on absorbance, fluorescence and DOC measurements. Detailed protocols of
      membrane cleaning and conditioning nation are proposed. The ultrafiltration
      membrane can efficiently be cleaned to provide low carbon blank (<0.01 mg/L).
      Fluorescence measurements confirmed that the higher molecular weight compounds
      were isolated in the retentate and the lower molecular weight remain in the
      permeate. Mass balance for natural samples show good recovery for DOC (109 +/-
      12%, n = 20) and fluorescence measurements (106 +/- 9%, n = 13). No relation
      between factors of concentration (fc) and mass balance quality was observed for
      the fc range 1.5-11. Moreover, high ionic strength and high DOC contents did not
      enhance membrane fouling. These findings demonstrate that reliable fractionations
      by TFF of natural organic colloids in aquatic systems can be achieved.

PMID- 12044068
TI  - Trichloroethylene adsorption by activated carbon preloaded with humic substances:
      effects of solution chemistry.
AB  - Trichloroethylene (TCE) adsorption by activated carbon previously loaded
      ("preloaded") with humic substances was found to decrease with increasing
      concentrations of monovalent ions (NaCl), calcium (until solubility was
      exceeded), or dissolved oxygen in the preloading solution. For a given percentage
      of organic carbon removal during humic acid loading, greater reductions in TCE
      adsorption occurred with increasing monovalent ion concentration and calcium
      concentration at constant ionic strength. However, this effect was related
      primarily to the amount of humic material adsorbed--the reduction in TCE
      adsorption was independent of the ionic composition of the preloading solution
      when compared at similar humic acid loading. Experiments were performed which
      showed that calcium ions can associate with humic material after the humic has
      been adsorbed, which subsequently reduces TCE uptake, but this effect does not
      dominate when calcium is present during humic loading. At sufficiently high
      calcium concentrations (approaching solubility), aggregation or co-precipitation
      of humic acid mitigated the effects of preloading. In contrast to the effects of
      ionic composition, the presence of dissolved oxygen did fundamentally change the
      mechanism by which organic macromolecules compete with TCE. TCE uptake was lower
      when preloading by poly(maleic acid) (PMA) occurred in the presence of dissolved
      oxygen, even when the amount loaded was the same. One explanation invokes a
      coupling mechanism promoted by the carbon surface, which results in either
      additional blockage of TCE sorption sites, additional site competition, or both.
      In all experiments, the effects of preloading were consistent with those reported
      previously, which have been interpreted as a loss of high-energy sites available
      to TCE, causing a significant reduction in the site-energy heterogeneity, and
      reduced uptake in the low concentration region.

PMID- 12044069
TI  - Biotransformation of 2,4,6-trinitrotoluene in a continuous-flow Anabaena sp.
      system.
AB  - Reductive transformation of 2,4,6-trinitrotoluene (TNT) was observed in a
      continuous-flow system of Anabaena sp. operated for 33 d with a 5.7 d hydraulic
      retention time and a range of influent TNT concentrations of 1-58 mg/l. The TNT
      removal efficiency of the continuous-flow system at the highest influent TNT
      concentration of 58 mg/l was 96.7 +/- 1.7% (mean +/- 95% confidence interval).
      Culture chlorosis and growth inhibition were not observed during this study. The
      pseudo-first order TNT transformation rate constant values corresponding to the
      system performance range (0.14-0.46/h) were lower than the values previously
      recorded for batch Anabaena sp. cultures with less than 10 mg/l initial TNT
      concentrations, possibly due to an inhibition of the TNT transformation process
      by either TNT and/or TNT transformation products. Heterotrophic bacterial
      populations developed in the continuous-flow Anabaena sp. cultures also
      transformed TNT, but at a much lower rate than the Anabaena sp. Less than 1% of
      the overall TNT transformation observed in the continuous-flow system was
      attributed to the heterotrophic bacterial populations. The only TNT reduction
      products identified in both the culture media and in biomass extracts were
      azoxytetranitrotoluene isomers and low levels of aminodinitrotoluene isomers. TNT
      and TNT transformation products identified in the culture effluent and the
      biomass extract accounted for only about 24% of the TNT added to the system (on a
      molar basis). Production of soluble, polar metabolites, uptake, partial
      mineralization and/or sequestration of TNT and its transformation products by
      Anabaena may be responsible for the relatively low contaminant recovery and mass
      balance observed in this study.

PMID- 12044070
TI  - Biodegradation of propylene glycol and associated hydrodynamic effects in sand.
AB  - At airports around the world, propylene glycol (PG) based fluids are used to de
      ice aircraft for safe operation. PG removal was investigated in 15-cm deep
      saturated sand columns. Greater than 99% PG biodegradation was achieved for all
      flow rates and loading conditions tested, which decreased the hydraulic
      conductivity of the sand by 1-3 orders of magnitude until a steady-state minimum
      was reached. Under constant loading at 120 mg PG/d for 15-30 d, the hydraulic
      conductivity (K) decreased by 2-2.5 orders of magnitude when the average linear
      velocity of the water was 4.9-1.4 cm/h. Variable PG loading in recirculation
      tests resulted in slower conductivity declines and lower final steady-state
      conductivity than constant PG feeding. After significant sand plugging,
      endogenous periods of time without PG resulted in significant but partial
      recovery of the original conductivity. Biomass growth also increased the
      dispersivity of the sand.

PMID- 12044071
TI  - Effect of water purification on its radioactive content.
AB  - We have analyzed the dissolved activity of various radionuclides of natural
      origin (226Ra and (234,235,235)U) and artificial origins (90Sr and (239+240)Pu),
      together with other non-radioactive physico-chemical parameters (pH,
      conductivity, dry residue, [Ca2+], [Mg2+], [K+] and [Fe(2+,3+)], in both pre
      potable and potable water from 17 treatment plants in Extremadura (Spain). We
      have established a series of criteria and complementary techniques to the
      traditional methods of purification, aimed at the quantitative elimination of the
      presence in solution of the mentioned radionuclides. We highlight: (a) the
      increment of the mineral content of the water in its treatment succeeds in
      eliminating 226Ra, until reaching values close to 70%; (b) the increment of the
      mineralization of the water by addition of chemical reagents, conducted within
      the pH values 7.1 and 7.8, succeeds in eliminating up to 90% of the total uranium
      in dissolution; (c) the elimination of 90Sr during the purification is poor, in
      general, reaching average levels of only 15% when the purification process is
      practiced within concrete ranges for potable water (pH > 7, conductivity > 150
      microS/cm, dry residue > 150 mg/l, [Ca2+] > 10 mg/l and [Mg2+] > 1.2 mg/l), and
      finally, (d) the decrease of the solubility of the iron, as low as it can get
      during the purification process, together with an increase of the conductivity
      associated, in principle, to parallel increments of other variables not analyzed
      in this work, such as SO4(2-), CO3(2-), etc., the activity of dissolved
      (239+240)Pu decreases to 90%. The application of the traditional processes of
      water purification outside the ranges and criteria formulated can increase the
      presence in dissolution up to 400%, for some radionuclides, largely the
      consequence of its redissolution from the non-soluble fraction of the water.

PMID- 12044072
TI  - Faecal-indicator concentrations in waters draining lowland pastoral catchments in
      the UK: relationships with land use and farming practices.
AB  - Faecal-indicator budget studies have shown marine bathing water quality at two
      small UK coastal resorts, Staithes and Newport, to be adversely affected by
      riverine inputs from lowland pastoral catchments (J. Chartered Inst. Water
      Environ. Mangt. 12 (1998) 414). The present paper reports on presumptive coliform
      (PC), presumptive Escherichia coli (PE) and presumptive streptococci (PS)
      concentrations at 43 sampling points on watercourses within these catchments, and
      on their relationship with land use and livestock-related management practices,
      such as grazing and slurry/manure applications. The results show > 10-fold
      elevations in geometric mean faecal-indicator concentrations under high-flow
      conditions, compared with low flow, with maximum high-flow geometric mean PC, PE
      and PS concentrations of 2.6 x 10(6), 1.8 x 10(6) and 4.4 x 10(5) cfu/100 ml,
      respectively. High-flow geometric mean concentrations exhibit highly significant
      positive correlations with land use/management variables associated with
      intensive livestock farming, both within the individual catchments and in the two
      combined. Additional factors, such as antecedent weather conditions and
      topography, contribute to inter-catchment variability in water quality. Although
      inputs from diffuse and point sources of pollution were not quantified, point
      sources (e.g. runoff from farm yards) seem likely to be significant. The findings
      suggest that it may be possible to develop generic statistical models to predict
      microbial water quality from land use and farm management data. They also provide
      indirect evidence that channel bed sediment 'stores' closely reflect land use
      within their catchments and that there is little die-off of organisms along
      watercourses.

PMID- 12044073
TI  - Reduction in photosynthetic efficiency of Cladophora glomerata, induced by
      overlying canopies of Lemna spp.
AB  - The duckweeds Lemna minor L. and L. minuscula Herter reduced PSII quantum
      efficiency (F'q/F'm) of the filamentous green alga Cladophora glomerata Kutzing
      by up to 42% over seven days when floating above mats of C. glomerata in
      containers. Dissolved oxygen (DO) increased by 23% at 30 degrees C in containers
      with C. glomerata over controls. But when the water surface in the containers was
      covered with Lemna spp. floating above C. glomerata, DO was 83% lower at 30
      degrees C over seven days than in control samples with no duckweed or alga.
      Dissolved oxygen was lower beneath a thick mat (1 cm) of either Lemna spp.
      covering the surface than under a thin layer (single-frond canopy). PAM
      fluorimetry showed that maximum PSII efficiency (Fv/Fm) of C. glomerata in
      containers was reduced under a canopy of L. minor by 17% over seven days, and
      under L. minuscula by 22%. F'q/F'm of C. glomerata in containers exposed to 51
      micromol m(-2) s(-1) PPFD decreased under a canopy of L. minor by 16% over seven
      days, and under L. minuscula by 19% compared to controls. When light response
      curves were compared, F'q/F'm was significantly reduced under canopies of L.
      minor at the highest temperatures tested (28 degrees C and 30 degrees C). L.
      minor significantly reduced relative electron transport rate (rel. ETR) of the
      controls by up to 71% at 30 degrees C. Relative electron transport rate did not
      reach light saturation point (Esat) except at 28 degrees and 30 degrees C under
      mats of L. minor. Whereas the highest rate of production (rel. ETRmax) and Esat
      increased with temperature in controls, under a canopy of Lemna, decreases were
      observed. It is suggested that, during periods of high summer temperature and
      irradiance, shading inhibits oxygenic photosynthesis in mats of C. glomerata
      beneath canopies of Lenma spp. This results in less oxygen being produced by the
      C. glomerata (oxygen produced by Lemna spp. is not released into the water), and
      this may further inhibit the C. glomerata by limiting oxygen-dependent electron
      transport and/or photorespiration. This feedback loop could lead to the eventual
      senescence of the C. glomerata. The combination of low oxygen, high temperature
      and stressed filamentous algae, particularly in slow or standing water, may help
      to explain sudden collapses in DO concentration, with detrimental effects on
      water quality downstream.

PMID- 12044074
TI  - Analysis and predictive models of stormwater runoff volumes, loads, and pollutant
      concentrations from watersheds in the Twin Cities metropolitan area, Minnesota,
      USA.
AB  - Urban nonpoint source pollution is a significant contributor to water quality
      degradation. Watershed planners need to be able to estimate nonpoint source loads
      to lakes and streams if they are to plan effective management strategies. To meet
      this need for the twin cities metropolitan area, a large database of urban and
      suburban runoff data was compiled. Stormwater runoff loads and concentrations of
      10 common constituents (six N and P forms, TSS, VSS, COD, Pb) were characterized,
      and effects of season and land use were analyzed. Relationships between runoff
      variables and storm and watershed characteristics were examined. The best
      regression equation to predict runoff volume for rain events was based on
      rainfall amount, drainage area, and percent impervious area (R2 = 0.78). Median
      event-mean concentrations (EMCs) tended to be higher in snowmelt runoff than in
      rainfall runoff, and significant seasonal differences were found in yields
      (kg/ha) and EMCs for most constituents. Simple correlations between explanatory
      variables and stormwater loads and EMCs were weak. Rainfall amount and intensity
      and drainage area were the most important variables in multiple linear regression
      models to predict event loads, but uncertainty was high in models developed with
      the pooled data set. The most accurate models for EMCs generally were found when
      sites were grouped according to common land use and size.

PMID- 12044075
TI  - Nitrate removal by a combination of elemental sulfur-based denitrification and
      membrane filtration.
AB  - In this paper, a new method for removal of nitrate from groundwater, in which
      elemental sulfur-based denitrification (autotrophic denitrification) and membrane
      separation are combined, is proposed. By using a membrane, autotrophic
      denitrifiers, whose growth rate is considerably low, can be kept at a high
      concentration. The performance of the proposed process was examined through a
      long-term experiment in the laboratory using synthetic feed water. A rotating
      membrane disk module equipped with UF membrane (750,000 Da) was used in this
      study. Complete removal of nitrate (25 mg N/L) was achieved under the conditions
      of a biomass concentration of about 1000 mg protein/L and HRT of 160 min.
      Dissolved oxygen concentration and sulfur/biomass ratio in the membrane chamber
      were found to be the key factors in maintenance of high-process performance.
      Deterioration in membrane permeability was insignificant. It was found that
      membrane filtration could be continued with a water flux of 0.5 m3/m2/day for
      about 100 days without any chemical membrane cleaning. The proposed process,
      however, caused a slight increase in assimilable organic carbon. Sulfide was not
      detected in the denitrified water.

PMID- 12044076
TI  - Characterization of microbial community in granular sludge treating brewery
      wastewater.
AB  - The diversity and distribution of microbes within brewery-degrading anaerobic
      sludge granules were studied using various molecular techniques. Molecular
      cloning of small-subunit rRNA gene sequences indicated that all archaeal clones
      were affiliated with Methanosaeta concillii (>99% sequence similarity), and the
      bacterial clones were mostly affiliated with a not-yet-cultured Clostridium
      cluster (48 out of 99 clones) in the low G + C gram-positive group, Xanthomonas
      spp. in the gamma-subclass of Proteobacteria (30 clones), and Desulfovibrio spp.
      (16 clones) in the delta-subclass of Proteobacteria. Slot-blot hybridization
      indicated that archaeal cells from the Methanomicrobiales (58.4% of total rRNA),
      Methanobacterials (3.3%) and Methanococcales (1.0%) accounted for 62.4% of the
      total community rRNA. The rest of the microbial populations were the clostridial
      cluster (27.3% of total rRNA) and Desulfovibrio spp. (9.4%). Fluorescence in-situ
      hybridization with domain and group-specific oligonucleotide probes further
      revealed a multi-layer granular architecture. On the surface layer, the
      hydrolytic clostridial species and hydrogenotrophic Methanobacteriales were the
      predominant. In the middle layer, mostly H2-producing acetogens from the delta
      Proteobacteria (i.e., Desulfovibrio spp.), hydrogenotrophic Methanobacteriales
      and aceticlastic Methanosaeta were observed to presumably form a syntrophic
      association. Finally, the center core consisted of microcolonies of Methanosaeta
      cells.

PMID- 12044078
TI  - Kinetics of adsorption of Co(II) removal from water and wastewater by ion
      exchange resins.
AB  - The capacity of ion exchange resins, IRN77 and SKN1, for removal of cobalt from
      aqueous solution has been investigated under different conditions namely initial
      solution pH, initial metal-ion concentration, and contact time. The equilibrium
      data obtained in this study have been found to fit both the Langmuir and
      Freundlich adsorption isotherms. The adsorption of Co(II) on these resins follows
      first-order reversible kinetics. The film diffusion of Co(II) in these ion
      exchange resins was shown to be the main rate limiting step. The studies showed
      that these cation exchange resins can be used as efficient adsorbent material for
      the removal of Co(II) from aqueous solutions.

PMID- 12044077
TI  - Removal of paraquat dissolved in a photoreactor with TiO2 immobilized on the
      glass-tubes of UV lamps.
AB  - Experiments were performed to investigate the effects of operating parameters,
      such as air-inflow rate, UV-light intensity, and film thickness of the
      photocatalyst, on the photo-decomposition efficiency of paraquat in an immersion
      type reactor with TiO2 immobilized by three kinds of methods on the glass tube of
      UV lamps. As the number of TiO2 coating-time increased from 1 to 4, film
      thickness on the glass tube by a dip-coating method increased from 355 to 1180 A.
      The removal efficiency of paraquat using TiO2 prepared by the hydrothermal method
      was the highest, being 99% in a 12 h operation of 3-type TiO2 immobilized by a
      sol-gel method and a hydrothermal method, including a commercial product P-25,
      while that in the absence of TiO2 with only the UV light was the lowest, being
      50% in 12 h. The conversion ratios of paraquat at the volumetric flow rates of 5,
      10, and 20 mL min(-1) were 46%, 25%, and 17% in 18 h, respectively.

PMID- 12044079
TI  - Inhibition of p-cresol on aerobic biodegradation of carbazole, and sodium
      salicylate by Pseudomonas putida.
AB  - A PAH- and phenol-degrading microorganism, Pseudomonas putida (ATCC 17484), was
      used to study the substrate interactions during cell growth on carbazole
      containing mixtures with p-cresol and sodium salicylate. Both p-cresol and sodium
      salicylate could be utilised by the bacteria as the sole carbon and energy
      sources. When cells grew on the mixture of carbazole, p-cresol and sodium
      salicylate, strong substrate interactions were observed. Carbazole degradation
      started only after p-cresol was significantly or completely removed, and the
      removal of carbazole was incomplete when the initial p-cresol concentration was
      higher than 20 mg/l. No carbazole was removed at all when the initial p-cresol
      concentration in the system was higher than 120 mg/l. When cells grew on the
      ternary substrates, the specific growth rate was found to increase with p-cresol
      concentration up to 50 mg/l (from 0.33 to 0.45 h(-1)) but decreased monotonically
      with higher concentrations. At 120 mg/l p-cresol, specific growth rate fell to
      0.33 h(-1). The inhibitory effect of p-cresol was demonstrated where carbazole
      degradation was immediately halted when 50 mg/l p-cresol was spiked to a system
      containing carbazole and sodium salicylate. Besides, the addition of p-cresol was
      also found to inhibit the degradation of sodium salicylate. With p-cresol, an
      increase in lag time was observed and the utilisation of sodium salicylate as
      carbon source was severely retarded.

PMID- 12044080
TI  - Comparison of the filtration characteristics of organic and inorganic membranes
      in a membrane-coupled anaerobic bioreactor.
AB  - Comparison of filtration characteristics of organic and inorganic membranes was
      made in terms of physicochemical properties of the membrane materials, cake layer
      formation, backflushing and backfeeding effects in a membrane-coupled anaerobic
      bioreactor. For the inorganic membrane, struvite (MgNH4PO4 x 6H2O) was found to
      have accumulated inside the membrane pore and plays a key role in flux decline.
      For the organic, however, a thick cake layer composed of biomass and struvite
      formed on the membrane surface, thus causing a major hydraulic resistance. In
      order to mitigate flux decline for both membranes, backflushing and backfeeding
      modes were examined. With acidic (pH 2.0) backflushing, the flux was
      approximately doubled for the organic membrane. However, unexpectedly a negative
      effect was observed for the inorganic membrane. An alkaline backflushing instead
      of acidic backflushing gave rise to a flux improvement by a factor of two without
      any negative effect, even for the inorganic membrane. The backfeeding mode gave
      rise to a much higher flux compared with the normal mode in both types of
      membrane, although the flux returned to the same level as that with the normal
      mode after 6 days for the inorganic membrane. The differences between the two
      types of membranes were explained by membrane morphology, a ligand exchange
      reaction as well as a surface charge effect.

PMID- 12044081
TI  - Characteristics of metal removal using carboxylated alginic acid.
AB  - Carboxylated alginic acid prepared through oxidation reaction with potassium
      permanganate had a high uptake capacity of 3.1 mmol/g dry mass at pH 4 and showed
      higher affinity to heavy metals compared to alkaline metals (Ca2+, Mg2+) in mixed
      metal system. The pHzpc value of the carboxylated alginic acid was 2.31, which
      was lower than pHzpc (2.83) of natural alginic acid. The increased number of
      carboxyl groups was confirmed by IR and 13C-NMR spectrum analysis, elemental
      analysis and carboxyl group number count. Lead adsorption by carboxylated alginic
      acid is an endothermic process since binding was increased as the temperature
      increased. When the temperature of wastewater is higher than room temperature,
      carboxylated alginic acid has an advantage over general adsorbents whose uptake
      capacity decreases as the temperature increases. Also, lead adsorbed on
      carboxylated alginic acid was desorbed effectively by about 80% by
      nitrilotriaceticacid.

PMID- 12044082
TI  - Optimisation of sulphate reduction in a methanol-fed thermophilic bioreactor.
AB  - Several methods were tested to optimise sulphate reduction and minimise methane
      formation in thermophilic (65 degrees) expanded granular sludge bed reactors fed
      with a medium containing sulphate and methanol. Lowering the pH from 7.5 to 6.75
      resulted in a rapid decrease of methane formation and a concomitant increase in
      sulphate reduction. The inhibition of methane formation was irreversible on the
      short-term. Lowering the COD/SO4(2-) ratio (COD: chemical oxygen demand) from 6
      to 0.34 (g/g) rapidly favoured sulphate reduction over methanogenesis. Continuous
      addition of 2 g L(-1) 2-bromoethanesulphonate was ineffective as complete
      inhibition of methanogenesis was obtained only for two days. Inhibition of
      methanogens by sulphide at pH 7.5 was only effective when the total sulphide
      concentration was above 1200 mg S L(-1). For practical applications, a relatively
      short exposure to a slightly acidic pH in combination with operating the reactor
      at a volumetric methanol-COD loading rate close to the maximum volumetric
      sulphide-COD formation rate.

PMID- 12044083
TI  - Potential phosphorus recovery by struvite formation.
AB  - Formation of struvite (MgNH4PO4 x 6H2O) at sewage treatment works can cause
      operational problems and decrease efficiency. Struvite has a commercial value and
      the controlled formation and recovery of it would be beneficial. A mass balance
      was conducted at full scale across the whole sewage treatment plant in order to
      identify a stream to conduct bench-scale struvite crystallisation studies. The
      most suitable stream was identified as the centrifuge liquors. The average flow
      of the liquor stream was 393 m3 d(-1) and the composition was as follows: 167 mg
      L(-1) phosphorus, 44 mg L(-1) magnesium, 615 mg L(-1) ammonium, 56 mg L(-1)
      calcium and 2580 mg L(-1) of alkalinity. The pH averaged at 7.6 and the stream
      had a predicted struvite precipitation potential of 140 mg L(-1). Struvite
      crystallisation occurred quickly during the trials, by raising the pH of the
      centrifuge liquors to 9.0 and dosing with magnesium. Up to 97% phosphorus removal
      as struvite was achieved. Struvite formation occurred when the molar ratio of
      magnesium:phosphorus was at least 1.05:1. Below this ratio phosphorus removals of
      72% were observed, but not exclusively as struvite. Annual yields of struvite
      were calculated to be 42-100 tonnes a year, depending on the dose regime. Revenue
      from the sale of produced struvite could be between Pound Sterling8400 and Pound
      Sterling20,000 a year.

PMID- 12044084
TI  - Physical modelling of solute transport in porous media: evaluation of an imaging
      technique using UV excited fluorescent dye.
AB  - The development and evaluation of a 2-dimensional physical model, which is
      designed to assist in the characterisation of complex solute transport problems
      in porous media, is described. The laboratory model is a transparent 2
      dimensional porous media of nominal thickness and uses a non-invasive imaging
      technique in conjunction with a fluorescent dye tracer (sodium fluorescein) to
      monitor solute movements. Under ultraviolet (UV) illumination the dye emits
      visible light which is imaged by a CCD (Charge Coupled Device) camera. The image
      is processed to estimate the 2-dimensional distribution of tracer concentrations.
      The system can successfully model a simple contaminant plume within a homogenous
      porous matrix constructed from glass beads (60-100 microm). Experimental results
      show that transverse dispersion coefficient was 3.9 x 10(-10) m2/s when sodium
      fluorescein transported in porous matrix with a walter velocity of 5.71 x 10(-6)
      m/s. The low transverse dispersion coefficient suggests that the molecular
      diffusion of solute cannot be neglected under low velocity of the water. The
      advantages of using UV rather than an ordinary light system are a reduction in
      noise and experimental errors. Errors due to light dispersion within the model
      are shown to be negligible for the current model. Since contaminant with aromatic
      rings are usually fluorescent and biological samples can be labelled by
      fluorescent dye, this imaging technique using UV excited fluorescent dye will be
      used to investigate biodegradation process in porous media.

PMID- 12044085
TI  - Hydro-environmental modelling for bathing water compliance of an estuarine basin.
AB  - In recent years, considerable investment has been committed to sewerage
      infrastructure and new sewage treatment plants in the catchment surrounding an
      estuarine basin along the north-west coast of England. Although this capital
      investment has resulted in a marked reduction in the input of bacterial loads,
      relatively high counts of faecal indicator organisms are still being encountered
      in the coastal receiving waters, and the local bathing waters continue to fail on
      occasions to comply with the European Community (EC) Bathing Water Directive
      (1976) mandatory standards. Details are given herein of a comprehensive modelling
      study aimed at quantifying the impact of various bacterial inputs into the
      estuary and surrounding coastal waters on the bathing water quality. The model
      domain includes the coastal area and the entire estuary (namely the Ribble) up to
      the tidal limits of its tributaries. Faecal coliforms have been used as the main
      water quality indicator organisms. The numerical model developed for this study
      combines a depth integrated two-dimensional coastal model and a cross-sectionally
      integrated one-dimensional river model, and is capable of predicting water
      surface elevations, velocity fields and faecal coliform concentration
      distributions across the entire model domain. The hydrodynamic model was
      calibrated using water level and velocity measurements from three surveys and
      then validated against measured data from three other surveys. In order to
      predict the faecal coliform concentration distributions, variable faecal coliform
      decay rates were used, i.e. different values of decay rates were applied to the
      coastal and riverine waters, for day- and nighttime, and for wet and dry weather
      conditions. The maximum and minimum decay rates used were 2.32/day and 0.71/day
      for the dry and wet weather surveys, respectively. The model was then applied to
      (i) assess the impact of previous discharge strategies and investigate the
      effectiveness of future capital investment works and (ii) predict the impact of a
      range of strategic options, including: the effects of adding UV treatment,
      constructing storm water storage tanks and incorporating various combined sewer
      overflow (CSO) discharge scenarios for different weather conditions.

PMID- 12044086
TI  - Mesophilic and thermophilic activated sludge post-treatment of paper mill process
      water.
AB  - Increasing system closure in paper mills and higher process water temperatures
      make the applicability of thermophilic treatment systems increasingly important.
      The use of activated sludge as a suitable thermophilic post-treatment system for
      anaerobically pre-treated paper process water from a paper mill using recycled
      wastepaper was studied. Two lab-scale plug flow activated sludge reactors were
      run in parallel for 6 months; a thermophilic reactor at 55 degrees C and a
      reference reactor at 30 degrees C. Both reactors were operated simultaneously at
      20, 15 and 10 days SRT. The effects of temperature and SRT on sludge
      settleability and chemical oxygen demand (COD) removal efficiencies of different
      fractions were studied. Total COD removal percentages over the whole experimental
      period were 58+/-5% at 30 degrees C and 48 +/- 10% at 55 degrees C. The effect of
      the SRT on the total COD removal was negligible. Differences in total COD removal
      between both systems were due to a lesser removal of soluble and colloidal COD at
      55 degrees C compared to the reference system. At 30 degrees C, colloidal COD
      removal percentages were 65+/-25%, 75+/-17% and 86+/-22% at 20, 15 and 10 days
      SRT, respectively. At 55 degrees C, these percentages were 48+/-34%, 40+/-28% and
      70+/-25%, respectively. The effluent concentrations of colloidal COD in both
      systems were related to the influent concentration of colloidal material. The
      thermophilic sludge was not able to retain influent colloidal material as well as
      the mesophilic sludge causing a higher thermophilic effluent turbidity. Sludge
      settling properties were excellent in both reactor systems. These were neither
      temperature nor SRT dependent but were rather caused by extensive calcium
      precipitation in the aeration tanks creating a very dense sludge. For application
      in the board industry, a thermophilic in line treatment system seems feasible.
      The higher effluent turbidity is most likely offset by the energy gains of
      treatment under thermophilic conditions.

PMID- 12044087
TI  - Occurrence of Cryptosporidium in agricultural surface waters during an annual
      farming cycle in lowland UK.
AB  - A 17-month survey based on weekly testing for Cryptosporidium oocysts in surface
      waters draining a livestock farm on a Warwickshire (UK) estate has shown that the
      parasite is present throughout the year, with the highest frequency of occurrence
      and maximum concentrations during the autumn and winter. The 190 ha farm is
      managed as an exemplar for a teaching institution. There were up to 800 livestock
      present at peak times of year in the catchment of the stream draining the estate.
      Oocysts were concentrated from grab samples by a flocculation procedure, stained
      with monoclonal antibody and detected by fluorescence microscopy. Overall,
      274/418 (66%) of samples were positive for Cryptosporidium. Where the stream
      passed from the estate, the occurrence was 79%, with mean and median oocysts/l of
      0.48 and 0.2, respectively. Highest oocyst levels coincided with calving and
      increased wild animal numbers following breeding. There was no correlation of
      oocyst levels with rainfall or slurry spreading. Cryptosporidium was also
      frequently found in a pond on arable land (no livestock) indicating that wild
      animals alone contributed oocysts to surface waters. These results from a well
      managed livestock farm may represent a typical natural baseline for levels of
      occurrence and concentration of Cryptosporidium oocysts in surface waters of the
      lowland agricultural environment of the UK.

PMID- 12044088
TI  - Grey-box modelling of aeration tank settling.
AB  - A model of the concentrations of suspended solids (SS) in the aeration tanks and
      in the effluent from these during Aeration tank settling (ATS) operation is
      established. The model is based on simple SS mass balances, a model of the sludge
      settling and a simple model of how the SS concentration in the effluent from the
      aeration tanks depends on the actual concentrations in the tanks and the sludge
      blanket depth. The model is formulated in continuous time by means of stochastic
      differential equations with discrete-time observations. The parameters of the
      model are estimated using a maximum likelihood method from data from an
      alternating BioDenipho waste water treatment plant (WWTP). The model is an
      important tool for analyzing ATS operation and for selecting the appropriate
      control actions during ATS, as the model can be used to predict the SS amounts in
      the aeration tanks as well as in the effluent from the aeration tanks.

PMID- 12044089
TI  - Biodegradation of a polymeric dye in a pulsed bed bioreactor by immobilised
      phanerochaete chrysosporium.
AB  - An immobilised fungal bioreactor operated with pulsation of the gas-phase is
      proposed and operated at variable conditions for the continuous biological
      degradation of complex structures. In order to test the system, a hardly
      biodegradable dye (Poly R-478) was selected as a model compound and Phanerochaete
      chrysosporium as the ligninolytic fungus. High percentages of decolourisation-
      between 65% and 80%--under optimal conditions were achieved. Moreover, the system
      proved to have high stability with long operational periods (at least, 90 days).
      During the operation Manganese Peroxidase was the sole ligninolytic enzyme
      detected which points out this enzyme as the main substance responsible for
      decolourisation. The optimal conditions established were the following:
      temperature of 37 degrees C, use of oxygen, Mn2+ concentrations between 33 and
      330 microM and exogenous H2O2 added in periodical pulses (as chemical reagent, 1
      microM or as H2O2 enzymatically generated by 0.6 U L(-1) glucose oxidase and
      residual glucose).

PMID- 12044090
TI  - Infrared detection of chlorinated hydrocarbons in water at ppb levels of
      concentrations.
AB  - Infrared sensor, based on attenuated total reflection phenomenon, for the
      detection of chlorinated hydrocarbons (CHCs) represents a big advantage compared
      to chromatographic and mass spectroscopic techniques since it is a one step
      detector. Pre-concentration and separation take place in the polymer film with
      simultaneous identification of pollutants by the infrared beam. The analysis is
      rapid, sample does not require any initial preparation, and can be easily
      performed in the field. The main default of the latest version of the sensor was
      a low sensibility (above 1 ppm) compared to the threshold levels of the
      contaminants. In the present work, it is documented that the response dynamics of
      the optical sensor and its sensitivity depend strongly on the diffusion of
      pollutants through a boundary layer formed between polymer film and the monitored
      solution and in the polymer film. The reduction of thickness of the boundary
      layer through a controlled high flow rate, and the optimization of thickness
      (volume) of polymer films result in a tremendous improvement of the response
      dynamics. It is demonstrated that the sensor can detect simultaneously six CHCs:
      monochlorobenzene, 1,2-dichlorobenzene, 1,2,4-trichlorobenzene, chloroform,
      trichloroethylene, and perchloroethylene in their mixture with a sensitivity as
      low as a few ppb. This level of detection opens up numerous applications for the
      optical sensor.

PMID- 12044091
TI  - Determination of chlorinated pesticides in water by SPME/GC.
AB  - Solid-phase microextraction (SPME) followed by gas chromatography (GC) coupled
      with an electron capture detector has been applied for the analysis of
      chlorinated pesticides in water. Molecule adsorption on 100 microm
      polydimethylsiloxane (PDMS) fibers was activated by immersion of the whole fiber
      sample system in an ultrasonic bath. The good reproducibility, low detection
      limits and wide linear ranges obtained encourage the use of this technique in
      water control.

PMID- 12044092
TI  - Determination of zinc levels in waters from southeastern Spain by electrothermal
      atomic absorption spectrometry: relationship with industrial activity.
AB  - An efficient method for the determination of nanogram levels of zinc in waters
      (potable, irrigation, waste and sea waters) is described. Acidified water samples
      were analyzed by an accurately optimized time/temperature program for
      electrothermal atomic absorption spectrometry. The samples were previously
      treated with a matrix modifier consisting of 0.1% Mg(NO3)2 in 0.5 M HNO3 and
      injected through a graphite tube with L'Vov platform. Sample recoveries,
      repeteability, and analyses of NIST reference material demonstrated the
      reliability and accuracy of this technique. Zinc concentrations ranged from 2.0
      to 73.0 microg l(-1). No significant differences among the mean zinc levels
      determined in the four types of water considered from southeastern Spain were
      found. Zinc concentrations in waters from the zone were not affected by human and
      industrial activity.

PMID- 12044093
TI  - The head and the hands.

PMID- 12044094
TI  - Experiments on the role of painted cues in Hughes's reverspectives.
AB  - The English artist Patrick Hughes has created an extraordinary class of painted
      artpieces, most commonly referred to as 'reverspectives'. They consist of
      truncated pyramids and prisms with their smaller faces closer to the viewer, in
      such a way as to allow a realistic scene to be painted on them. The works of art
      contain rich perspective and other painted cues that conspire to elicit an
      illusory depth percept that is the reverse of the physical depth arrangement.
      This reverse depth is obtained under a wide range of viewing conditions, and
      competes with the veridical depth percept in a classical bistable paradigm that
      was found to exhibit a high degree of hysteresis. Under the illusory depth
      percept, reverspectives appear to move vividly as the viewer moves in front of
      them. This paper reports two experiments that were designed to assess the
      effectiveness of the painted cues in eliciting the illusory depth percept by
      using three different measures for the strength of the illusion. As expected, the
      illusion was favored by monocular viewing and large viewing distances. The
      results from these two experiments are in close agreement with each other, and
      they indicate that the painted cues are powerful in influencing the ultimate
      percept.

PMID- 12044095
TI  - Perceptual assignment of opacity to translucent surfaces: the role of image blur.
AB  - In constructing the percept of transparency, the visual system must decompose the
      light intensity at each image location into two components one for the partially
      transmissivc surface, the other for the underlying surface seen through it.
      Theories of perceptual transparency have typically assumed that this
      decomposition is defined quantitatively in terms of the inverse of some physical
      model (typically, Metelli's 'episcotister model'). In previous work, we
      demonstrated that the visual system uses Michelson contrast as a critical image
      variable in assigning transmittance to transparent surfaces not luminance
      differences as predicted by Metelli's model [F Metelli, 1974 Scientific American
      230(4) 90 98]. In this paper, we study the contribution of another variable in
      determining perceived transmittance, namely, the image blur introduced by the
      light-scattering properties of translucent surfaces and materials. Experiment 1
      demonstrates that increasing the degree of blur in the region of transparency
      leads to a lowering in perceived transmittance, even if Michelson contrast
      remains constant in this region. Experiment 2 tests how this addition of blur
      affects apparent contrast in the absence of perceived transparency. The results
      demonstrate that, although introducing blur leads to a lowering in apparent
      contrast, the magnitude of this decrease is relatively small, and not sufficient
      to explain the decrease in perceived transmittance observed in experiment 1. The
      visual system thus takes the presence of blur in the region of transparency as an
      additional image cue in assigning transmittance to partially transmissive
      surfaces.

PMID- 12044096
TI  - Configural face processing develops more slowly than featural face processing.
AB  - Expertise in face processing takes many years to develop. To determine the
      contribution of different face-processing skills to this slow development, we
      altered a single face so as to create sets of faces designed to measure featural,
      configural, and contour processing. Within each set, faces differed only in the
      shape of the eyes and mouth (featural set), only in the spacing of the eyes and
      mouth (spacing set), or only in the shape of the external contour (contour set).
      We presented adults, and children aged 6, 8, and 10 years, with pairs of upright
      and inverted faces and instructed them to indicate whether the two faces were the
      same or different. Adults showed a larger inversion effect for the spacing set
      than for the featural and external contour sets, confirming that the spacing set
      taps configural processing. On the spacing set, all groups of children made more
      errors than adults. In contrast, on the external contour and featural sets,
      children at all ages were almost as accurate as adults, with no significant
      difference beginning at age 6 on the external contour set and beginning at age 10
      on the featural set. Overall, the results indicate that adult expertise in
      configural processing is especially slow to develop.

PMID- 12044097
TI  - Categorical perception of race.
AB  - Traditionally, research demonstrating categorical perception (CP) has assumed
      that CP occurs only in cases where natural continua are divided categorically by
      long-term learning or innate perceptual programming. More recent research
      suggests that this may not be true, and that even novel continua between novel
      stimuli such as unfamiliar faces can show CP effects as well. Given this, we ask
      whether CP is dependent solely on the representation of individual stimuli, or
      whether stimulus categories themselves can also cause CP. Here, we test the
      hypothesis that continua between individual faces that cross the categorical
      boundary between races show an enhanced CP effect. We find that continua running
      from a black face to a white face do, indeed, show stronger CP effects than
      continua between two black faces or two white faces. This suggests that CP
      effects are enhanced when continua run between two distinctly represented
      individual stimuli, and are further enhanced when those individuals are, in turn,
      members of different stimulus categories.

PMID- 12044098
TI  - A feature-segmentation model of short-term visual memory.
AB  - A feature-segmentation model of short-term visual memory (STVM) for contours is
      proposed. Memory of the First stimulus is maintained until the second stimulus is
      observed. Three processes interact to determine the relationship between stimulus
      and response: feature encoding, memory, and decision. Basic assumptions of the
      model are twofold: (i) the STVM system divides a contour into convex parts at
      regions of concavity; and (ii) the value of each convex part represented in STVM
      is an independent Gaussian random variable. Simulation showed that the five
      parameter fits give a good account of the effects of the four experimental
      variables. The model provides evidence that: (i) contours are successfully
      encoded within 0.5 s exposure, regardless of pattern complexity; (ii) memory
      noise increases as a linear function of retention interval; (iii) the capacity of
      STVM, defined by pattern complexity (the degree that a pattern can be handled for
      several seconds with little loss), is about 4 convex parts; and (iv) the
      confusability contributing to the decision process is a primary factor in
      deteriorating recognition of complex figures. It is concluded that visually
      presented patterns can be retained in STVM with considerable precision for
      prolonged periods of time, though some loss of precision is inevitable.

PMID- 12044099
TI  - Detection performance in pop-out tasks: nonmonotonic changes with display size
      and eccentricity.
AB  - We carried out three experiments to investigate detection performance in pop-out
      tasks and analysed how performance varied as a function of display size (number
      of elements) and retinal eccentricity of the target. Results showed that when
      display size was increased from 2 to 81 elements performance first decreased and
      then increased (replicating Sagi and Julesz, 1987 Spatial Vision 2 39-49).
      Performance variations differed as a function of eccentricity and often were more
      pronounced in the periphery than in the foveal area. This retinal-eccentricity
      influence suggests that processes underlying detection performance in small
      display sizes are different from those in large display sizes. One should be
      careful when using the variation of display size as an instrument to analyse
      visual-search processes because this analysis could be based on a comparison
      between non-equivalent conditions.

PMID- 12044100
TI  - Motion versus position in the perception of head-centred movement.
AB  - Abstract. Observers can recover motion with respect to the head during an eye
      movement by comparing signals encoding retinal motion and the velocity of
      pursuit. Evidently there is a mismatch between these signals because perceived
      head-centred motion is not always veridical. One example is the Filehne illusion,
      in which a stationary object appears to move in the opposite direction to
      pursuit. Like the motion aftereffect, the phenomenal experience of the Filehne
      illusion is one in which the stimulus moves but does not seem to go anywhere.
      This raises problems when measuring the illusion by motion nulling because the
      more traditional technique confounds perceived motion with changes in perceived
      position. We devised a new nulling technique using global-motion stimuli that
      degraded familiar position cues but preserved cues to motion. Stimuli consisted
      of random-dot patterns comprising signal and noise dots that moved at the same
      retinal 'base' speed. Noise moved in random directions. In an eye-stationary
      speed-matching experiment we found noise slowed perceived retinal speed as
      'coherence strength' (ie percentage of signal) was reduced. The effect occurred
      over the two-octave range of base speeds studied and well above direction
      threshold. When the same stimuli were combined with pursuit, observers were able
      to null the Filehne illusion by adjusting coherence. A power law relating
      coherence to retinal base speed fit the data well with a negative exponent. Eye
      movement recordings showed that pursuit was quite accurate. We then tested the
      hypothesis that the stimuli found at the null-points appeared to move at the same
      retinal speed. Two observers supported the hypothesis, a third partially, and a
      fourth showed a small linear trend. In addition, the retinal speed found by the
      traditional Filehne technique was similar to the matches obtained with the global
      motion stimuli. The results provide support for the idea that speed is the
      critical cue in head-centred motion perception.

PMID- 12044101
TI  - The limited capacity of humans to identify the components of taste mixtures and
      taste-odour mixtures.
AB  - The capacity of humans to identify the components of taste mixtures and odour
      taste mixtures was investigated in two experiments. Subjects were trained to
      identify the components presented alone and to use a 'yes/no' procedure to
      identify them in mixtures. All stimuli were presented with a retronasal (by
      mouth) technique. A maximum of three tastants were identified in both types of
      mixtures, only one tastant was identified in five-component taste mixtures, and
      no component was identified in four-component odour-taste mixtures. Importantly,
      in no instance was the olfactory stimulus identified in any mixture with tastes,
      including binary mixtures. Loss of identity of the odorant in binary and ternary
      mixtures may have been due to suppression as a consequence of temporal
      processing, or to the absence of an association between the odorant and tastants
      that had established an identifiable percept. In contrast, poor identification of
      the components of the quaternary odour-taste mixture and quinternary taste
      mixture is attributed to the limited capacity of working memory. Overall, the
      poorer ability to identify components in odour-taste mixtures than in taste
      mixtures indicates that interactions occurred between the two senses, challenging
      the proposal that odours and tastes are processed independently when present in
      complex chemosensory stimuli.

PMID- 12044102
TI  - Orientation-dependent contrast.

PMID- 12044103
TI  - The long-term clinical course of generalized anxiety disorder.
AB  - Although generalized anxiety disorder (GAD) is a common disorder associated with
      significant levels of morbidity, little is known of its long-term course and
      outcomes. During the first 5 years, GAD follows a chronic course with low rates
      of remission and moderate rates of relapse/recurrence following remission.
      Retrospective studies suggest that this chronic pattern may last up to 20 years.
      It is hoped that, as with depression, long-term prospective studies in GAD will
      provide insight into the course, nature, and outcomes of the disorder over time.
      The studies will also identify any changes in the duration and severity of
      episodes of GAD over time, enabling treatments to effectively reflect the course
      of the disorder. Studies of other anxiety disorders and depression suggest that
      the course and outcome of the disorder may be influenced by certain factors such
      as stressful life events, anxiety sensitivity/negative affect, gender,
      subsyndromal symptoms, and comorbid disorders. Currently, studies are underway to
      determine the effects of these factors on the risk of relapse/recurrence,
      maintenance of full symptoms, and development of subsyndromal symptoms in GAD.
      GAD is currently underrecognized and undertreated, but it is hoped that this will
      change with the ever-increasing awareness of anxiety disorders. As treatment for
      GAD becomes more common, future prospective studies will identify the effect of
      therapy on the course and nature of the disorder, leading to increased
      understanding of GAD and the development of effective treatment strategies
      tailored for individual patients.

PMID- 12044104
TI  - Treatment of generalized anxiety disorder.
AB  - Generalized anxiety disorder (GAD) is characterized by chronic worry that may
      persist for many years. It is a debilitating disorder, and effective long-term
      treatment is required. Psychotherapy, particularly relaxation, cognitive therapy,
      and cognitive-behavioral therapy, has shown long-term benefit in GAD and may be a
      useful approach alone and as an adjunct to pharmacotherapeutic options. Available
      medications for GAD include benzodiazepine anxiolytics, buspirone, and
      antidepressants. Although benzodiazepines are effective as short-term
      anxiolytics, their use is compromised by a poor adverse event profile and, like
      buspirone, they lack the antidepressant efficacy important for addressing the
      comorbid depression experienced by many patients with GAD. Antidepressants,
      including paroxetine and the serotonin-norepinephrine reuptake inhibitor
      venlafaxine, are effective anxiolytics and resolve symptoms of depression in
      patients with GAD. The benefit of venlafaxine is sustained long term, enabling
      increased numbers of patients to attain remission from symptoms and experience
      restoration of normal functioning. Although further clinical studies are required
      to establish the use of psychosocial therapy in the treatment of GAD. preliminary
      results are encouraging. At present, the use of psychosocial therapy and second
      generation antidepressants, such as some selective serotonin reuptake inhibitors
      and venlafaxine, offer the best approach to attaining long-term benefit for
      patients with GAD.

PMID- 12044105
TI  - Generalized anxiety and depression in primary care: prevalence, recognition, and
      management.
AB  - AIMS: Determine attitudes toward patients with generalized anxiety disorder (GAD)
      and major depressive episodes (MDE) in primary care; determine prevalence of GAD,
      MDE, and comorbid GAD/MDE among primary care patients; assess physician
      recognition of GAD and MDE; and describe primary care interventions for these
      patients. METHOD: 558 primary care physicians participated in a 1-day survey.
      Over 20,000 patients completed a diagnostic-screening questionnaire for GAD and
      MDE. Physician questionnaires included a standardized clinical appraisal of
      somatic and psychosocial symptoms and information on past and current treatments
      and a prestudy questionnaire assessing experience with and attitudes toward
      patients with GAD and MDE. RESULTS: 56.9% of physicians viewed GAD as a genuine
      mental disorder with clinical management problems and considerable patient
      burden; 27.4% treated GAD patients differently from MDE patients. 5.3% of
      patients met criteria for GAD, 6.0% for MDE, 3.8% for pure GAD, 4.4% for pure
      MDE, and 1.6% for comorbid GAD/MDE. Pure GAD and MDE were associated with
      disability, high utilization of health care resources, and suicidality, which
      were even higher with comorbid GAD/MDE. Physicians recognized clinically
      significant emotional problems in 72.5% of patients with pure GAD, 76.5% with
      pure MDE, and 85.4% with comorbid GAD/MDE. However, correct diagnosis was much
      lower (64.3% for MDE and 34.4% for GAD). Although the majority of patients with
      recognized GAD or MDE were treated, only a small minority with GAD were
      prescribed medications or referred to specialists. CONCLUSION: The high
      proportion of respondents with pure GAD is inconsistent with previous reports
      that GAD is usually comorbid with depression. GAD remains poorly recognized and
      inadequately treated. Improving the recognition and treatment of GAD in primary
      care patients is discussed relative to new treatments.

PMID- 12044106
TI  - Generalized anxiety disorder in primary care: emerging issues in management and
      treatment.
AB  - Generalized anxiety disorder (GAD) is highly prevalent in primary care patients
      and is a source of major morbidity. The low rate of recognition and diagnosis of
      GAD is often the result of insufficient knowledge on the part of primary care
      physicians, time pressures, and competing demands during patients' visits.
      Patient attribution of symptoms and the stigma related to mental illness also
      contribute to underrecognition. Other contributing factors include the natural
      history of GAD, the bimodal age of presentation, a chronic but waxing and waning
      course, frequent comorbidity with other anxiety and depressive disorders, and the
      controversy regarding the best diagnostic criteria. However, proper diagnosis is
      critical to appropriate management. Primary care management of GAD and associated
      comorbidities includes education about the nature of GAD as a medical disorder
      that is amenable to treatment and counseling about treatment alternatives and
      coping strategies. Most patients with GAD suffer from insomnia, and treating
      insomnia can be of great benefit to them. While cognitive-behavioral therapy and
      relaxation therapy are effective in treating GAD, most patients in primary care
      settings are likely to require pharmacologic treatment. Although commonly used,
      benzodiazepines and their short-term benefits are overshadowed by their decreased
      long-term effectiveness, their minimal treatment of psychic symptoms, and their
      degradation of patient performance. The selective serotonin reuptake inhibitor
      (SSRI) paroxetine is indicated for the short-term treatment of GAD, although
      adequate data supporting the use of most SSRIs for GAD are not yet available. The
      serotonin-norepinephrine reuptake inhibitor venlafaxine provides a treatment
      option resulting in both short- and long-term improvement of symptoms, attaining
      not only a response but also remission from GAD and prevention of relapse.

PMID- 12044108
TI  - Tackling hunger, disease and 'internal security': official medical administration
      in colonial eastern India during the Second World War (part II).

PMID- 12044107
TI  - Patterns and correlates of generalized anxiety disorder in community samples.
AB  - BACKGROUND: Although generalized anxiety disorder (GAD) is at least twice as
      prevalent as panic disorder and is among the commonly occurring mental disorders,
      changing diagnostic criteria have hampered the cumulation of data on patterns and
      correlates. METHOD: A computer literature search was carried out for the terms
      generalized anxiety disorder and GAD in the MEDLINE and PsycLIT databases.
      Reports published in English since 1995 were reviewed to determine patterns and
      correlates of GAD in the general population. RESULTS: The literature shows
      clearly that GAD is a commonly occurring disorder associated with serious
      impairment. Although the high comorbidities of GAD with other disorders in
      clinical samples led to speculation that the impairments associated with GAD were
      due to comorbid conditions, several recent studies show that pure GAD is
      associated with serious impairments. Considerable uncertainty remains regarding
      appropriate diagnostic criteria. The requirements that the anxiety be excessive
      and persist for 6 months are the subject of the most controversy. Recently
      reported community epidemiologic data show that generalized anxiety syndromes
      that persist for shorter time periods and that are not excessive in relation to
      objective stressors are as seriously impairing as syndromes that meet full
      criteria for GAD. It is less clear whether currently available treatments are as
      useful in resolving episodes of generalized anxiety that lie outside the
      boundaries of current ICD and DSM criteria. CONCLUSION: GAD is a commonly
      occurring mental disorder that can seriously impair functioning. Coordinated
      community epidemiologic studies and treatment effectiveness studies are needed to
      resolve remaining uncertainties regarding the diagnostic boundaries of GAD.

PMID- 12044109
TI  - Surgical management of casualties in a low-intensity war.

PMID- 12044110
TI  - The Association of Rural Surgeons of India.

PMID- 12044111
TI  - It's time the twain meets.

PMID- 12044112
TI  - Communal riots: a deja vu.

PMID- 12044113
TI  - Another bridge across the digital divide.

PMID- 12044114
TI  - Ethics and public health policies.

PMID- 12044115
TI  - Maternal mortality in India: no room for complacence.

PMID- 12044116
TI  - The CRASH trial: the first large-scale randomized controlled trial in head
      injury. Corticosteroid Randomization After Significant Head injury.

PMID- 12044117
TI  - Hypertension and its risk factors in tea garden workers of Assam.
AB  - BACKGROUND: Hypertension is emerging as a major public health problem in India.
      The diversity and heterogeneity of distribution of the population makes it
      difficult to arrive at the precise prevalence. In Assam, reports from hospitals
      in tea gardens reveal a high prevalence of hypertension among workers in tea
      gardens. However, no systematic study has been carried out in this population.
      METHODS: We selected, by systematic sampling, 1015 individuals (512 men and 503
      women) 30 years or more in age, who were interviewed and clinically examined for
      hypertension. Blood pressure of all the study participants was measured using a
      standardized technique. Crude and adjusted odds ratios were estimated by
      unconditional simple and multiple logistic regression analyses. Mantel-Haenszel
      chi2 analysis was also used to test for the association of potential risk factors
      with hypertension after controlling for co-variables in a stratified analysis.
      Risk factors considered for hypertension included age, gender, marital status,
      occupation, alcohol consumption (locally prepared), extra salt intake, smoking
      history, khaini (a form of tobacco quid containing a mixture of tobacco and lime)
      intake, body mass index and waist-hip ratio. RESULTS: The overall prevalence of
      hypertension was 60.8%. Increasing age, consumption of locally prepared alcohol,
      intake of extra salt in food and beverages and the habit of taking khaini were
      found to increase the risk of hypertension. Multivariate logistic regression
      models showed that the independent determinants of hypertension were age, gender,
      consumption of locally prepared alcohol and intake of extra salt. Gender-specific
      and age-stratified analyses showed the association of increased risk with intake
      of khaini in women only, while consumption of locally prepared alcohol was an
      important risk factor for hypertension in both men and women. CONCLUSION: The
      disease burden of hypertension among workers in tea gardens is large, despite the
      community not being obese. Interventions directed at these workers as well as
      studies to determine the reasons for the high prevalence of hypertension are
      required.

PMID- 12044118
TI  - Awareness of post-exposure prophylaxis guidelines against occupational exposure
      to HIV in a Mumbai hospital.
AB  - BACKGROUND: Exposure to the human immunodeficiency virus (HIV) is a matter of
      concern for healthcare workers. We conducted a survey to determine the level of
      awareness amongst operating room personnel regarding post-exposure prophylaxis in
      case of needlestick injuries from confirmed or suspected cases of HIV. METHODS: A
      structured questionnaire was presented to 39 anaesthetists and 31 surgical
      residents. Questions were related to identification of high risk fluids, risk of
      transmission, drugs, costs and procedure to be adopted for post-exposure
      prophylaxis. RESULTS: Fourteen respondents (20%) were aware of the true risk of
      transmission. About one-third identified all high risk fluids correctly. Fifty
      five respondents (78%) correctly stated that washing the site with soap and water
      was the initial measure, but less than a third knew whom to contact immediately
      after a needlestick injury. Though 45 respondents (64%) correctly stated that
      prophylaxis should be initiated within 1 hour of injury, none knew exactly which
      drugs were to be used. Thirty respondents (42%) were aware of the use of
      zidovudine but none were aware of the second or third drugs used for post
      exposure prophylaxis. Only 4 respondents (6%) knew the correct duration of post
      exposure prophylaxis. Five respondents (7%) knew that the drugs were available in
      medical stores and 7 knew the approximate cost of therapy. CONCLUSION: There is
      surprisingly poor knowledge of post-exposure prophylaxis against HIV. Ongoing
      awareness and training programmes are necessary to improve the same.

PMID- 12044119
TI  - Parasitic diarrhoea in patients with AIDS.
AB  - BACKGROUND: Diarrhoea is a common clinical manifestation of HIV infection
      regardless of whether or not patients have AIDS. Two newly recognized
      opportunistic coccidial protozoa are parasitic pathogens in AIDS patients. We
      attempted to determine the common parasites in Indian patients with AIDS.
      METHODS: Between October 1994 and December 1996, a total of 110 stool specimens
      from 94 AIDS patients with acute or chronic diarrhoea were examined by microscopy
      of wet mounts and smears stained by a modified Ziehl-Neelsen's (cold) staining
      method. RESULTS: Isospora belli was the most frequently encountered parasite in
      17% of patients, followed by Entamoeba histolytica in 14.9% and Cryptosporidium
      in 8.5%. Strongyloides stercoralis and Giardia lamblia were detected in 5.3% and
      4.3% of patients, respectively. CONCLUSION: The presence of different parasites
      in 56.4% of stool specimens of patients with AIDS indicates that their specific
      diagnosis is essential. This will help initiate therapy to reduce the morbidity
      and mortality among such patients due to these pathogens.

PMID- 12044120
TI  - Rapid prenatal karyotyping using foetal blood obtained by cordocentesis.
AB  - BACKGROUND: Prenatal karyotyping using foetal blood samples obtained by
      cordocentesis is a useful method of detecting abnormal chromosomes in the foetus.
      METHODS: Cordocentesis was performed in 187 cases for prenatal karyotyping
      between January 1995 and September 2000. Pregnant women were between 18 and 38
      weeks of gestation and their ages ranged from 18 to 40 years. The common
      indications were ultrasonographic abnormalities (47.6%), history of previous Down
      syndrome (13.3%), advanced maternal age (11.7%), low maternal serum alpha
      foetoprotein levels (10.7%), previous child with malformation (10.7%), previous
      child with trisomy (chromosome 13/18) (2.6%), parent a balanced translocation
      carrier (1.6%) and high maternal serum alpha foetoprotein levels (1.6%). RESULTS:
      Analysis of 137 successful cultures showed 8 (5.2%) karyotype abnormalities. The
      remaining samples could not be reported due to the presence of maternal
      contamination of the sample (12.3%), inadequate sample (6.4%) or culture failure
      (9.8%). In those with an abnormal karyotype, obstetric management could be
      altered appropriately. CONCLUSION: In foetuses at high risk of a chromosomal
      aberration, a rapidly obtained karyotype is helpful in obstetric management.

PMID- 12044121
TI  - Non-haematological functions of platelets.

PMID- 12044122
TI  - Eye trauma: primary care for general physicians.

PMID- 12044123
TI  - Priority setting in the health sector: why is a good cause-of-death reporting
      system important?

PMID- 12044124
TI  - Clinical trials in India sponsored by the pharmaceutical industry: a proposal for
      reforms.

PMID- 12044125
TI  - Ethical issues in public health policy.
AB  - Ethics in public health policy is given the least importance and rarely
      discussed. Resolving ethical issues in public health is often an arduous task as
      these are complicated and require careful handling. Using four case studies, we
      discuss issues pertaining to pertussis and brain damage, water fluoridation and
      dental caries, infection with the human immunodeficiency virus and the right to
      marriage, and the debate surrounding universal salt iodization. The core issue in
      all these examples pertains to the relevance of ethics in public health policy.

PMID- 12044127
TI  - Chlorhexidine compared with povidone-iodine solution for vascular catheter-site
      care: a meta-analysis.
AB  - PURPOSE: Bloodstream infections related to use of catheters, particularly central
      line catheters, are an important cause of patient morbidity, mortality, and
      increased health care costs. This study evaluated the efficacy of skin
      disinfection with chlorhexidine gluconate compared with povidone-iodine solution
      in preventing catheter-related bloodstream infection. DATA SOURCES: Multiple
      computerized databases (1966 to 2001), reference lists of identified articles,
      and queries of principal investigators and antiseptic manufacturers. STUDY
      SELECTION: Randomized, controlled trials comparing chlorhexidine gluconate with
      povidone-iodine solutions for catheter-site care. DATA EXTRACTION: Using a
      standardized form, two reviewers abstracted data on study design, patient
      population, intervention, and incidence of catheter-related bloodstream infection
      from all included studies. DATA SYNTHESIS: Eight studies involving a total of
      4143 catheters met the inclusion criteria. All studies were conducted in a
      hospital setting, and various catheter types were used. The summary risk ratio
      for catheter-related bloodstream infection was 0.49 (95% CI, 0.28 to 0.88) in
      patients whose catheter sites were disinfected with chlorhexidine gluconate
      instead of povidone-iodine. Among patients with a central vascular catheter,
      chlorhexidine gluconate reduced the risk for catheter-related bloodstream
      infection by 49% (risk ratio, 0.51 [CI, 0.27 to 0.97]). CONCLUSIONS: These
      results suggest that incidence of bloodstream infections is significantly reduced
      in patients with central vascular lines who receive chlorhexidine gluconate
      versus povidone-iodine for insertion-site skin disinfection. Use of chlorhexidine
      gluconate is a simple and effective means of reducing vascular catheter-related
      infections.

PMID- 12044126
TI  - Mechanism of cocaine-induced hyperthermia in humans.
AB  - BACKGROUND: The lethal effects of cocaine are unique among those of other illicit
      drugs because cocaine has the propensity to cause hyperthermia. The traditional
      view is that cocaine causes a hypermetabolic state with increased heat
      production. However, because cocaine-induced hyperthermia occurs primarily in hot
      weather, it is hypothesized that cocaine also impairs thermoregulatory
      adjustments that mediate heat dissipation. OBJECTIVE: To test the effects of
      cocaine on body temperature regulation in humans. DESIGN: Randomized, double
      blind, placebo-controlled crossover trial. SETTING: A cardiovascular physiology
      laboratory in Dallas, Texas. PARTICIPANTS: 7 healthy, cocaine-naive volunteers.
      INTERVENTION: Progressive passive heat stress, during which each participant
      received intranasal cocaine (2 mg/kg of body weight) or placebo (lidocaine, 2
      mg/kg). MEASUREMENTS: Esophageal temperature, skin blood flow, sweat rate, and
      perceived thermal sensation. RESULTS: Three major new findings were noted. First,
      cocaine substantially augmented the progressive increase in esophageal
      temperature during heat stress (P < 0.001). Second, this augmentation was
      explained by a rightward shift in the esophageal temperature threshold for the
      onset of both cutaneous vasodilation (37.37 +/- 0.09 degrees C for cocaine vs.
      37.06 +/- 0.07 degrees C for lidocaine; P = 0.01) and sweating (37.38 +/- 0.09
      degrees C for cocaine vs. 37.07 +/- 0.06 degrees C for lidocaine; P = 0.002).
      Third, cocaine paradoxically impaired the perception of heating by attenuating
      the progressive increase in thermal discomfort associated with heat stress.
      CONCLUSIONS: In humans, impaired heat dissipation is a major mechanism by which
      cocaine elevates body temperature. When healthy, cocaine-naive persons are
      subjected to passive heating, pretreatment with even a small dose of intranasal
      cocaine impairs sweating and cutaneous vasodilation (the major autonomic
      adjustments to thermal stress) and heat perception (the key trigger for
      behavioral adjustments).

PMID- 12044128
TI  - Clinical assessment of function among women with a recent cerebrovascular event:
      a self-reported versus performance-based measure.
AB  - BACKGROUND: Self-reported functional status is a commonly used health measure in
      clinical settings, yet the optimal approach for assessing function is often
      debated. OBJECTIVE: To examine the agreement between a self-reported and a
      performance-based measure of function and the relative ability of each measure to
      predict long-term health outcomes. DESIGN: Prospective cohort study. SETTING: 20
      hospitals in Connecticut and Massachusetts. PARTICIPANTS: 620 postmenopausal
      women (46 to 91 years of age) who had experienced a stroke or transient ischemic
      attack. MEASUREMENTS: A self-reported and a performance-based measure of function
      were assessed at baseline (before intervention) by using the Barthel index and
      the Physical Performance Test. RESULTS: Disagreement between the self-reported
      and performance-based measure of function was common (slight disagreement, 55.0%;
      substantial disagreement, 19.3%). Most women (95.4%) overreported their level of
      function. Women who were more clinically impaired (risk ratio [RR] for more
      comorbid conditions, 1.52 [95% CI, 1.17 to 1.97]; RR for recent stroke, 2.33 [CI,
      1.45 to 3.73]; and RR for cognitive impairment, 1.76 [CI, 1.34 to 2.32]); who
      were less educated (RR = 1.30 [CI, 1.02 to 1.67]); and who were of nonwhite
      ethnicity (RR 1.43 [CI, 1.07 to 1.91]) were more likely to overreport their level
      of function. An impaired performance-based measure of function predicted
      subsequent stroke or death (hazard ratio, 1.50, [CI, 1.06 to 2.11]); however, an
      impaired self-reported measure of function was not likely to predict these
      outcomes. CONCLUSIONS: Clinicians should be aware that results of self-reported
      and performance-based measures of function can differ in women who have
      experienced a recent cerebrovascular event. Although more difficult to collect,
      results of a performance-based measure may provide information about long-term
      health outcomes that is not available from a self-reported measure.

PMID- 12044129
TI  - The reliability of medical record review for estimating adverse event rates.
AB  - BACKGROUND: The data used by the U.S. Institute of Medicine to estimate deaths
      from medical errors come from a study that relied on nurse and physician reviews
      of medical records to detect the errors. OBJECTIVE: To measure the reliability of
      medical record review for detecting adverse events and negligent adverse events.
      DESIGN: Medical record review. SETTING: Hospitalizations in Utah and Colorado in
      1992. MEASUREMENTS: After three independent reviews of 500 medical records, the
      following were measured: reliability and the effect of varying criteria for
      reviewer confidence in and reviewer agreement about the presence of adverse
      events. RESULTS: For agreements in judgments of adverse events among the three
      sets of reviews, the kappa statistics ranged from 0.40 to 0.41 (95% CIs ranged
      from 0.30 to 0.51) for adverse events and from 0.19 to 0.23 (CIs, 0.05 to 0.37)
      for negligent adverse events. Rates for adverse events and for negligent adverse
      events varied substantially depending on the degree of agreement and the level of
      confidence that was required among reviewers. CONCLUSION: Estimates of adverse
      event rates from medical record review, including those reported by the Institute
      of Medicine in its 2000 report on medical errors, are highly sensitive to the
      degree of consensus and confidence among reviewers.

PMID- 12044130
TI  - The placebo effect in alternative medicine: can the performance of a healing
      ritual have clinical significance?
AB  - In alternative medicine, the main question regarding placebo has been whether a
      given therapy has more than a placebo effect. Just as mainstream medicine ignores
      the clinical significance of its own placebo effect, the placebo effect of
      unconventional medicine is disregarded except for polemics. This essay looks at
      the placebo effect of alternative medicine as a distinct entity. This is done by
      reviewing current knowledge about the placebo effect and how it may pertain to
      alternative medicine. The term placebo effect is taken to mean not only the
      narrow effect of a dummy intervention but also the broad array of nonspecific
      effects in the patient-physician relationship, including attention; compassionate
      care; and the modulation of expectations, anxiety, and self-awareness. Five
      components of the placebo effect--patient, practitioner, patient-practitioner
      interaction, nature of the illness, and treatment and setting--are examined.
      Therapeutic patterns that heighten placebo effects are especially prominent in
      unconventional healing, and it seems possible that the unique drama of this realm
      may have "enhanced" placebo effects in particular conditions. Ultimately, only
      prospective trials directly comparing the placebo effects of unconventional and
      mainstream medicine can provide reliable evidence to support such claims.
      Nonetheless, the possibility of enhanced placebo effects raises complex
      conundrums. Can an alternative ritual with only nonspecific psychosocial effects
      have more positive health outcomes than a proven, specific conventional
      treatment? What makes therapy legitimate, positive clinical outcomes or
      culturally acceptable methods of attainment? Who decides?

PMID- 12044131
TI  - The wrong patient.
AB  - Among all types of medical errors, cases in which the wrong patient undergoes an
      invasive procedure are sufficiently distressing to warrant special attention.
      Nevertheless, institutions underreport such procedures, and the medical
      literature contains no discussions about them. This article examines the case of
      a patient who was mistakenly taken for another patient's invasive
      electrophysiology procedure. After reviewing the case and the results of the
      institution's "root-cause analysis," the discussants discovered at least 17
      distinct errors, no single one of which could have caused this adverse event by
      itself. The discussants illustrate how these specific "active" errors interacted
      with a few underlying "latent conditions" (system weaknesses) to cause harm. The
      most remediable of these were absent or misused protocols for patient
      identification and informed consent, systematically faulty exchange of
      information among caregivers, and poorly functioning teams.

PMID- 12044132
TI  - The commonality of risk factors for nosocomial colonization and infection with
      antimicrobial-resistant Staphylococcus aureus, enterococcus, gram-negative
      bacilli, Clostridium difficile, and Candida.
AB  - Recent years have witnessed a rapidly growing crisis in antimicrobial resistance,
      especially among microorganisms that cause nosocomial infection. To better
      understand common risk factors among multiresistant organisms, this review
      explores risk factors for nosocomial infection with methicillin-resistant
      Staphylococcus aureus, vancomycin-resistant enterococcus, Clostridium difficile,
      extended-spectrum beta-lactamase-producing gram-negative bacilli, and Candida.
      This review comprises data from 74 published studies; 53 (71%) were retrospective
      studies and addressed few risk factors or did not quantify risk. The analysis
      shows impressive commonality of risk factors across these diverse multiresistant
      organisms: advanced age; underlying diseases and severity of illness; inter
      institutional transfer of the patient, especially from a nursing home; prolonged
      hospitalization; gastrointestinal surgery or transplantation; exposure to
      invasive devices of all types, especially central venous catheters; and exposure
      to antimicrobial drugs, especially cephalosporins. More restricted use of
      antibiotics, especially cephalosporins, and strategies to prevent medical device
      related infection and cross-infection in the hospital would yield benefit with
      all types of resistant organisms. Preemptive isolation of all patients with risk
      factors for infection by resistant organisms would very likely reduce secondary
      spread within the hospital. Conversely, programs that focus on only one organism
      or one antimicrobial drug are unlikely to succeed. Prospective studies of
      sufficient size that address all potential risk factors, especially individual
      anti-infective agents, and that use matched controls who are shown by
      surveillance cultures to be free of colonization by resistant organisms would
      enhance understanding of the epidemiology of antimicrobial resistance in
      institutions and guide efforts to develop more effective strategies for
      prevention.

PMID- 12044133
TI  - Sedation, alimentation, hydration, and equivocation: careful conversation about
      care at the end of life.
AB  - In the recent medical ethics literature, several authors have recommended
      terminal sedation and refusal of hydration and nutrition as important, morally
      acceptable, and relatively uncontroversial treatment options for end-of-life
      suffering. However, not all authors use these terms to refer to the same
      practices. This paper examines the various ways that the terms terminal sedation
      and refusal of hydration and nutrition have been used in the medical literature.
      Although some of these practices are ethically appropriate responses to end-of
      life suffering, others (at least as they are currently described in the medical
      ethics literature) are not. This paper identifies and discusses the principles
      that morally distinguish these practices from one another and specifically
      describes different features of medical practices and moral principles that
      affect the moral acceptability of various medical treatments. These distinctions
      reveal the complexity of the issues surrounding terminal sedation and refusal of
      hydration and nutrition, a complexity that has not been adequately addressed in
      recent discussions.

PMID- 12044134
TI  - Learning from our mistakes: quality grand rounds, a new case-based series on
      medical errors and patient safety.

PMID- 12044138
TI  - The heartbreak of drug pricing.

PMID- 12044137
TI  - The heartbreak of drug pricing.

PMID- 12044140
TI  - Molecular genetic evidence of an association between nasal polyposis and the
      Peutz-Jeghers syndrome.

PMID- 12044141
TI  - Summaries for patients. Body heat management in people using cocaine.

PMID- 12044142
TI  - Summaries for patients. Antiseptics to prevent infection from intravascular
      catheters.

PMID- 12044143
TI  - Summaries for patients. Evaluating function in women after a stroke using two
      different types of measures.

PMID- 12044144
TI  - Summaries for patients. The reliability of medical record review for estimating
      the frequency of medical mistakes.

PMID- 12044145
TI  - Tobacco use in HIV-infected women.

PMID- 12044146
TI  - Effects of pravastatin in the elderly.

PMID- 12044148
TI  - Vibration spectroscopy reveals light-induced chromophore and protein structural
      changes in the LOV2 domain of the plant blue-light receptor phototropin 1.
AB  - Phototropins (phot1 and phot2), the plant blue-light receptors for phototropism,
      chloroplast movement, and stomatal opening, are flavoproteins that contain two
      approximately 12 kDa FMN-binding domains, LOV1 and LOV2, at their N-terminus, and
      a serine/threonine protein kinase domain at their C-terminus. The light-activated
      LOV2 domain forms a metastable intermediate which has been shown to be a protein
      chromophore cysteinyl adduct (Cys39) at C(4a) of FMN. This species thermally
      relaxes back to the ground state in the dark. We measured the light-minus-dark
      FTIR difference spectra for the LOV2 domain of oat phot1. These spectra show the
      disappearance of bands at 1580, 1550, and 1350 cm(-1) that originate from, or are
      strongly coupled to, the N5=C(4a) stretching vibrations, consistent with the
      perturbations expected upon C(4a) adduct formation. Assignment of these negative
      difference FTIR bands to native chromophore vibrations is based on the alignment
      with resonance Raman bands of FMN. Prominent positive bands include a doublet at
      1516 and 1536 cm(-1) and one at 1375 and 1298 cm(-1). Normal-mode vibrational
      frequency calculations for both lumiflavin and lumiflavin with a sulfur attached
      at the C(4a) position agree with many of the positive and negative bands observed
      in the difference spectra. Both calculated and experimental difference FTIR
      spectra for deuterium isotope substitutions at exchangeable positions in the
      flavin chromophore are consistent with the assignment of the above positive bands
      to vibrational modes involving both the newly formed tetrahedral geometry of
      C(4a) and the N5-H bond in the long-lived LOV2(S)(390) cysteinyl species.

PMID- 12044149
TI  - Lipid dependence of membrane anchoring properties and snorkeling behavior of
      aromatic and charged residues in transmembrane peptides.
AB  - 31P NMR spectroscopy was used to investigate the effects of transmembrane alpha
      helical peptides with different flanking residues on the phase behavior of
      phosphatidylethanolamine and phosphatidylethanolamine/phosphatidylglycerol (molar
      ratio 7:3) model membranes. It was found that tryptophan-flanked (WALP) peptides
      and lysine-flanked (KALP) peptides both promote formation of nonlamellar phases
      in these lipid systems in a mismatch-dependent manner. Based on this mismatch
      dependence, it was concluded that the effective hydrophobic length of KALP
      peptides is considerably shorter than that of the corresponding WALP peptides.
      Peptides with other positively charged residues showed very similar effects as
      KALP. The results suggest that the peptides have a well-defined effective
      hydrophobic length, which is different for charged and aromatic flanking
      residues, but which is independent of the precise chemical nature of the side
      chain. Strikingly, the effective length of KALP peptides in the lipid systems
      investigated here is much smaller than that previously found for the same
      peptides in phosphatidylcholine. This suggests that snorkeling of lysine side
      chains, as proposed to occur in phosphatidylcholine, does not occur in lipid
      systems that are prone to form nonlamellar phases by themselves. This suggestion
      was supported by using peptides with shortened lysine side chains and by
      investigating the effects of mixtures of WALP and KALP peptides. The lipid
      dependency of the snorkeling behavior is explained by considering the free energy
      cost of snorkeling in relation to the free energy cost of the formation of
      nonlamellar phases.

PMID- 12044150
TI  - Overexpression and divalent metal binding properties of the methionyl
      aminopeptidase from Pyrococcus furiosus.
AB  - The gene encoding for the methionyl aminopeptidase from the hyperthermophilic
      archaeon Pyrococcus furiosus (PfMetAP-II; EC 3.4.11.18) has been inserted into a
      pET 27b(+) vector and overexpressed in Escherichia coli. The new expression
      system resulted in a 5-fold increase in purified enzyme obtained from a 5 L
      fermentor growth. The as-purified PfMetAP-II enzyme, to which no exogenous metal
      ions or EDTA was added, was found to have 1.2 equiv of zinc and 0.1 equiv of iron
      present by ICP-AES analysis. This enzyme had a specific activity of 5 units/mg, a
      60-fold decrease from the fully loaded Fe(II) enzymes. When an additional 2 equiv
      of Zn(II) was added to the as-purified PfMetAP-II, no activity could be detected.
      The combination of these data with previously reported whole cell studies on
      EcMetAP-I further supports the suggestion that the in vivo metal ion for all
      MetAP's is Fe(II). Both Co(II)- and Fe(II)-loaded PfMetAP-II showed similar
      substrate specificities to EcMetAP-I. Substrate binding was largely affected by
      the amino acid in the P1 position and the length of the polypeptide. The
      substrates MSSHRWDW and MP-p-NA showed the smallest K(m) values while the
      substrates MGMM and MP-p-NA provided the highest turnover. The catalytic
      efficiency (k(cat)/K(m)) of PfMetAP-II for MP-p-NA at 30 degrees C was 799 500
      and 340 930 M(-1) s(-1) for Co(II)- and Fe(II)-loaded PfMetAP-II, respectively.
      Maximum catalytic activity was obtained with 1 equiv of Co(II) or Fe(II), and the
      dissociation constants (K(d)) for the first metal binding site were found to be
      50 +/- 15 and 20 +/- 15 nM for Co(II)- and Fe(II)-substituted PfMetAP-II,
      respectively. Electronic absorption spectral titration of a 1 mM sample of apo
      PfMetAP-II with Co(II) provided a dissociation constant of 0.35 +/- 0.02 mM for
      the second metal binding site, a 17500-fold increase compared to the first metal
      binding site. The electronic absorption data also indicated that both Co(II) ions
      reside in a pentacoordinate geometry. PfMetAP-II shows unique thermostability and
      the optimal temperature for substrate turnover was found to be approximately 85
      degrees C at pH 7.5 in 25 mM Hepes and 150 mM KCl buffer. The hydrolysis of MGMM
      was measured in triplicate between 25 and 85 degrees C at eight substrate
      concentrations ranging from 2 to 20 mM. Both specific activity and K(m) values
      increased with increasing temperature. An Arrhenius plot was constructed from the
      k(cat) values and was found to be linear over the temperature range 25-85 degrees
      C, indicating that the rate-limiting step in PfMetAP-II peptide hydrolysis does
      not change as a function of temperature. Co(II)- and Fe(II)-loaded PfMetAP-II
      have similar activation energies (13.3 and 19.4 kJ/mol, respectively). The
      thermodynamic parameters calculated at 25 degrees C are as follows: DeltaG++ =
      46.23 kJ/mol, DeltaH++ = 10.79 kJ/mol, and DeltaS++ = -119.72 J.mol(-1).K(-1) for
      Co(II)-loaded PfMetAP; DeltaG++ = 46.44 kJ/mol, DeltaH++ = 16.94 kJ/mol, and
      DeltaS++ = -99.67 J.mol(-1).K(-1) for Fe(II)-loaded PfMetAP. Interestingly, at
      higher temperatures (> 50 degrees C), Fe(II)-loaded PfMetAP-II is more active
      (1.4-fold at 85 degrees C) than Co(II)-loaded PfMetAP-II.

PMID- 12044151
TI  - A highly potent artificial transcription factor.
AB  - The use of synthetic chemical moieties to design fully functional analogues of
      transcription factors will give rise to novel molecular tools for targeted gene
      regulation. Here we demonstrate that a synthetic molecule based on a nonpeptidic
      DNA-binding domain can be engineered to function as a highly potent transcription
      factor in vitro and in an intracellular context. The structure of this artificial
      transcription factor (ATF) consists of three parts: (i) triple-helix-forming
      oligonucleotide as a DNA-binding domain; (ii) composite linker moiety; and (iii)
      short synthetic peptide. The direct comparison of ATFs with natural transcription
      factors in in vitro assays reveals the ability of ATFs to initiate RNA
      transcription at the correct initiation site. In addition, the transcriptional
      activation potency of ATFs in vitro matches or exceeds the potency of GAL4-VP16,
      one of the strongest natural transcriptional activators. This remarkable
      biological activity is explained as a function of ATF's chemical structure. We
      also demonstrate for the first time that ATFs possess substantial ability to
      activate transcription in tissue culture cells, thus opening a prospect for
      practical applications in basic and applied research. The specific molecular
      design employed in the synthesis of ATFs may lead to the development of novel
      gene-targeting pharmaceuticals for treatment of fatal and chronic diseases.

PMID- 12044153
TI  - Stable DNA triple helix formation using oligonucleotides containing 2'
      aminoethoxy,5-propargylamino-U.
AB  - We have prepared oligonucleotides containing the novel base analogue 2'
      aminoethoxy,5-propargylamino-U in place of thymidine and examined their ability
      to form intermolecular and intramolecular triple helices by DNase I footprinting
      and thermal melting studies. The results were compared with those for
      oligonucleotides containing 5-propargylamino-dU and 2'-aminoethoxy-T. We find
      that the bis-substituted derivative produces a large increase in triplex
      stability, much greater than that produced by either of the monosubstituted
      analogues, which are roughly equipotent with each other. Intermolecular triplexes
      with 9-mer oligonucleotides containing three or four base modifications generate
      footprints at submicromolar concentrations even at pH 7.5, in contrast to the
      unmodified oligonucleotide, which failed to produce a footprint at pH 5.0, even
      at 30 microM. UV- and fluorescence melting studies with intramolecular triplexes
      confirmed that the bis-modified base produces a much greater increase in T(m)
      than either modification alone.

PMID- 12044152
TI  - DNA gyrase interaction with coumarin-based inhibitors: the role of the
      hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose.
AB  - DNA gyrase is a major bacterial protein that is involved in replication and
      transcription and catalyzes the negative supercoiling of bacterial circular DNA.
      DNA gyrase is a known target for antibacterial agents since its blocking induces
      bacterial death. Quinolones, coumarins, and cyclothialidines have been designed
      to inhibit gyrase. Significant improvements can still be envisioned for a better
      coumarin-gyrase interaction. In this work, we obtained the crystal costructures
      of the natural coumarin clorobiocin and a synthetic analogue with the 24 kDa
      gyrase fragment. We used isothermal titration microcalorimetry and differential
      scanning calorimetry to obtain the thermodynamic parameters representative of the
      molecular interactions occurring during the binding process between coumarins and
      the 24 kDa gyrase fragment. We provide the first experimental evidence that
      clorobiocin binds gyrase with a stronger affinity than novobiocin. We also
      demonstrate the crucial role of both the hydroxybenzoate isopentenyl moiety and
      the 5'-alkyl group on the noviose of the coumarins in the binding affinity for
      gyrase.

PMID- 12044154
TI  - Adaptor protein-2 exhibits alpha 1 beta 1 or alpha 6 beta 1 integrin-dependent
      redistribution in rhabdomyosarcoma cells.
AB  - Downregulation of several signaling pathways, such as those stimulated by growth
      factor receptors, occurs by internalization of signaling receptors through
      clathrin-coated pits. The first step in internalization or endocytosis is
      interaction with AP-2, which results in coated pit formation by assembly of
      clathrin to AP-2. Changes in endocytosis are reflected in the distribution of AP
      2 molecules at the cell surface. Integrins are receptors which mediate attachment
      to the extracellular matrix and also stimulate numerous intracellular signaling
      pathways; however, it is not known how signaling through integrins is terminated
      or downregulated. Endocytosis through clathrin-coated pits offers an attractive
      mechanism for this. This work explores the relationship between AP-2 and beta(1)
      integrins. RD cells grown for 24 h on collagen or laminin exhibit a
      redistribution of AP-2 to the cell periphery relative to those grown on
      fibronectin or polylysine. The total AP-2 protein levels in the cells are
      unaffected. Blocking alpha(1)beta(1) integrin ligand binding on collagen prevents
      this redistribution fully. On laminin where alpha(1)beta(1) and alpha(6)beta(1)
      integrins are engaged, both receptors must be simultaneously blocked to prevent
      AP-2 redistribution, confirming that the redistribution depends on the specific
      engagement of the receptors. Immunofluorescence reveals that the majority of
      alpha(1)beta(1) integrins colocalize with alpha(6)beta(1) integrins in linear
      structures identified as focal adhesions. A separate fraction of alpha(1)beta(1)
      integrins colocalize with AP-2 in coated pits. Interestingly, alpha(6)beta(1)
      integrins are not located in coated pits, demonstrating that integrin
      colocalization with AP-2 is not necessary to induce redistribution of AP-2.

PMID- 12044155
TI  - Evidence of an odorant-binding protein in the human olfactory mucus: location,
      structural characterization, and odorant-binding properties.
AB  - Odorant-binding proteins (OBPs) are small abundant extracellular proteins
      belonging to the lipocalin superfamily. They are thought to participate in
      perireceptor events of odor detection by carrying, deactivating, and/or selecting
      odorant molecules. Putative human OBP genes (hOBP) have recently been described
      [Lacazette et al. (2000) Hum. Mol. Genet. 9, 289-301], but the presence of the
      corresponding proteins remained to be established in the human olfactory mucus.
      This paper reports the first evidence of such expression in the mucus covering
      the olfactory cleft, where the sensory olfactory epithelium is located. On the
      contrary, hOBPs were not observed in the nasal mucus covering the septum and the
      lower turbinate. To demonstrate the odorant binding activity of these proteins, a
      corresponding recombinant protein variant, hOBP(IIa)(alpha), was secreted by the
      yeast Pichia pastoris and thoroughly characterized. It appears as a monomer with
      one disulfide bond located between C59 and C151, a conservative feature of all
      other vertebrate OBPs. By measuring the displacement of several fluorescent
      probes, we show that hOBP(IIa)(alpha) is able to bind numerous odorants of
      diverse chemical structures, with a higher affinity for aldehydes and large fatty
      acids. A computed 3D model of hOBP(IIa)(alpha) is proposed and reveals that two
      lysyl residues of the binding pocket may account for the increased affinity for
      aldehydes. The relatively limited specificity of hOBP(IIa)(alpha) suggests that
      other human OBPs are expected to take into account the large diversity of odorant
      molecules.

PMID- 12044157
TI  - Effects of T142 phosphorylation and mutation R145G on the interaction of the
      inhibitory region of human cardiac troponin I with the C-domain of human cardiac
      troponin C.
AB  - Cardiac troponin I (cTnI) is the inhibitory component of the troponin complex,
      and its interaction with cardiac troponin C (cTnC) plays a critical role in
      transmitting the Ca(2+) signal to the other myofilament proteins in heart muscle
      contraction. The switch between contraction and relaxation involves a movement of
      the inhibitory region of cTnI (cIp) from cTnC to actin-tropomyosin. This region
      of cTnI is prone to missense mutations in heart disease, and a specific mutation,
      R145G, has been associated with familial hypertrophic cardiomyopathy. It also
      contains the unique cardiac PKC phosphorylation site at residue T142. To
      determine the structural consequences of the mutation R145G and the T142
      phosphorylation on the interaction of cIp with cTnC, we have utilized 2D [(1)H,
      (15)N]-HSQC NMR spectroscopy to monitor the binding of native cIp, cIp-R (R145G),
      and cIp-P (phosphorylated T142), respectively, to the Ca(2+)-saturated C-domain
      of cTnC (cCTnC.2Ca(2+)). We also report a strategy for cloning, expression, and
      purification of cTnI peptide, and both synthetic and recombinant peptides are
      used in this study. NMR chemical shift mapping indicates that the binding epitope
      of cIp on cCTnC.2Ca(2+) is not greatly affected, but the affinity is reduced by
      approximately 14-fold by the T142 phosphorylation and approximately 4-fold by the
      mutation R145G, respectively. This suggests that these modifications of cIp have
      an adverse effect on the binding of cIp to cCTnC.2Ca(2+). These perturbations may
      correlate with the impairment or loss of cTnI function in heart muscle
      contraction.

PMID- 12044156
TI  - Organization of the membrane domain of the human liver sodium/bile acid
      cotransporter.
AB  - Mammalian sodium/bile acid cotransporters (SBATs) are glycoproteins with an
      exoplasmic N-terminus, an odd number of transmembrane regions, and a cytoplasmic
      C-terminus. Various algorithms predict eight or nine membrane-embedded regions
      derived from nine hydrophobic stretches of the protein (H1-H9). Three methods
      were used to define which of these were transmembrane or membrane-associated
      segments in the liver bile acid transporter. The first was in vitro
      translation/insertion scanning using either single hydrophobic sequences between
      the N-terminal domain of the alpha-subunit of the gastric H,K-ATPase and the C
      terminal domain of the beta-subunit that contains five N-linked glycosylation
      exoplasmic flags or using constructs beginning with the N-terminus of the
      transporter of various lengths and again ending in the C-terminus of the H,K
      ATPase beta-subunit. Seven of the predicted segments, but not the amphipathic H3
      and H8 sequences, insert as both individual signal anchor and stop transfer
      sequences in the reporter constructs. These sequences, H3 and H8, are contained
      within two postulated long exoplasmic loops in the classical seven-transmembrane
      segment model. The H3 segment acts as a partial stop transfer signal when
      expressed downstream of the endogenous H2. In a similar manner, the other
      amphipathic segment, H8, inserts as a signal anchor sequence when translated in
      the context with the upstream transporter sequence in two different glycosylation
      constructs. Alanine insertion scanning identified regions of the transporter
      requiring precise alignment of sequence to form competent secondary structures.
      The transport activity of these mutants was evaluated either in native protein or
      in a yellow fluorescent protein (YFP) fusion protein construct. All alanine
      insertions in H3 and H8 abolished taurocholate uptake, suggesting that both these
      regions have structures with critical intramolecular interactions. Moreover,
      these insertions also prevented trafficking to the plasma membrane as assessed by
      confocal microscopy with a polyclonal antibody against either the C-terminus of
      the transporter or the YFP signal of the YFP-transporter fusion protein. Two
      glycosylation signals inserted in the first postulated loop region and four of
      five such signals in the second postulated loop region were not recognized by the
      oligosaccharide transferase, and the L256N mutation exhibited 10% glycosylation
      and was inactive. These findings support a topography with nine membrane-spanning
      or membrane-associated segments.

PMID- 12044158
TI  - Functional characterization of spectrin-actin-binding domains in 4.1 family of
      proteins.
AB  - Protein 4.1R is the prototypical member of a protein family that includes 4.1G,
      4.1B, and 4.1N. 4.1R plays a crucial role in maintaining membrane mechanical
      integrity by binding cooperatively to spectrin and actin through its spectrin
      actin-binding (SAB) domain. While the binary interaction between 4.1R and
      spectrin has been well characterized, the actin binding site in 4.1R remains
      unidentified. Moreover, little is known about the interaction of 4.1R homologues
      with spectrin and actin. In the present study, we showed that the 8 aa motif
      (LKKNFMES) within the 10 kDa spectrin-actin-binding domain of 4.1R plays a
      critical role in binding of 4.1R to actin. Recombinant 4.1R SAB domain peptides
      with mutations in this motif showed a marked decrease in their ability to form
      ternary complexes with spectrin and actin. Binary protein-protein interaction
      studies revealed that this decrease resulted from the inability of mutant SAB
      peptides to bind to actin filaments while affinity for spectrin was unchanged. We
      also documented that the 14 C-terminal residues of the 21 amino acid cassette
      encoded by exon 16 in conjunction with residues 27-43 encoded by exon 17
      constituted a fully functional minimal spectrin-binding motif. Finally, we showed
      that 4.1N SAB domain was unable to form a ternary complex with spectrin and
      actin, while 4.1G and 4.1B SAB domains were able to form such a complex but less
      efficiently than 4.1R SAB. This was due to a decrease in the ability of 4.1G and
      4.1B SAB domain to interact with actin but not with spectrin. These data enabled
      us to propose a model for the 4.1R-spectrin-actin ternary complex which may serve
      as a general paradigm for regulation of spectrin-based cytoskeleton interaction
      in various cell types.

PMID- 12044160
TI  - Crystal structure of rat apo-heme oxygenase-1 (HO-1): mechanism of heme binding
      in HO-1 inferred from structural comparison of the apo and heme complex forms.
AB  - Heme oxygenase (HO) catalyzes the oxidative cleavage of heme to biliverdin by
      utilizing O(2) and NADPH. HO (apoHO) was crystallized as twinned P3(2) with three
      molecules per asymmetric unit, and its crystal structure was determined at 2.55 A
      resolution. Structural comparison of apoHO and its complex with heme (HO-heme)
      showed three distinct differences. First, the A helix of the eight alpha-helices
      (A-H) in HO-heme, which includes the proximal ligand of heme (His25), is
      invisible in apoHO. In addition, the B helix, a portion of which builds the heme
      pocket, is shifted toward the heme pocket in apoHO. Second, Gln38 is shifted
      toward the position where the alpha-meso carbon of heme is located in HO-heme.
      Nepsilon of Gln38 is hydrogen-bonded to the carbonyl group of Glu29 located at
      the C-terminal side of the A helix in HO-heme, indicative that this hydrogen bond
      restrains the angle between the A and B helices in HO-heme. Third, the amide
      group of Gly143 in the F helix is directed outward from the heme pocket in apoHO,
      whereas it is directed toward the distal ligand of heme in HO-heme. This means
      that the F helix around Gly143 must change its conformation to accommodate heme
      binding. The apoHO structure has the characteristic that the helix on one side of
      the heme pocket fluctuates, whereas the rest of the structure is similar to that
      of HO-heme, as observed in such hemoproteins as myoglobin and cytochromes b(5)
      and b(562). These structural features of apoHO suggest that the orientation of
      the proximal helix and the position of His25 are fixed upon heme binding.

PMID- 12044159
TI  - Interhelical interactions in the gp41 core: implications for activation of HIV-1
      membrane fusion.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein complex
      (gp120-gp41) promotes viral entry by mediating the fusion of viral and cellular
      membranes. Formation of a stable trimer-of-hairpins structure in the gp41
      ectodomain brings the two membranes into proximity, leading to membrane fusion.
      The core of this hairpin structure is a six-helix bundle in which three carboxyl
      terminal outer helices pack against an inner trimeric coiled coil. Here we
      investigate the role of these conserved interhelical interactions on the
      structure and function of both the envelope glycoprotein and the gp41 core. We
      have replaced each of the eight amino acids at the buried face of the carboxyl
      terminal helix with a representative amino acid, alanine. Structural and
      physicochemical characterization of the alanine mutants shows that hydrophobic
      interactions are a dominant factor in the stabilization of the six-helix bundle.
      Alanine substitutions at the Trp628, Trp631, Ile635, and Ile642 residues also
      affected envelope processing and/or gp120-gp41 association and abrogated the
      ability of the envelope glycoprotein to mediate cell-cell fusion. These results
      suggest that the amino-terminal region of the gp41 outer-layer alpha-helix plays
      a key role in the sequence of events associated with HIV-1 entry and have
      implications for the development of antibodies and small-molecule inhibitors of
      this conserved element.

PMID- 12044161
TI  - Structural studies on phospho-CDK2/cyclin A bound to nitrate, a transition state
      analogue: implications for the protein kinase mechanism.
AB  - Eukaryotic protein kinases catalyze the phosphoryl transfer of the gamma
      phosphate of ATP to the serine, threonine, or tyrosine residue of protein
      substrates. The catalytic mechanism of phospho-CDK2/cyclin A (pCDK2/cyclin A) has
      been probed with structural and kinetic studies using the trigonal NO(3)(-) ion,
      which can be viewed as a mimic of the metaphosphate transition state. The crystal
      structure of pCDK2/cyclin A in complex with Mg(2+)ADP, nitrate, and a
      heptapeptide substrate has been determined at 2.7 A. The nitrate ion is located
      between the beta-phosphate of ADP and the hydroxyl group of the serine residue of
      the substrate. In one molecule of the asymmetric unit, the nitrate is close to
      the beta-phosphate of ADP (distance from the nitrate nitrogen to the nearest beta
      phosphate oxygen of 2.5 A), while in the other subunit, the nitrate is closer to
      the substrate serine (distance of 2.1 A). Kinetic studies demonstrate that
      nitrate is not an effective inhibitor of protein kinases, consistent with the
      structural results that show the nitrate ion makes few stabilizing interactions
      with CDK2 at the catalytic site. The binding of orthovanadate was also
      investigated as a mimic of a pentavalent phosphorane intermediate of an
      associative mechanism for phosphoryl transfer. No vanadate was observed bound in
      a 3.4 A resolution structure of pCDK2/cyclin A in the presence of Mg(2+)ADP, and
      vanadate did not inhibit the kinase reaction. The results support the notion that
      the protein kinase reaction proceeds through a mostly dissociative mechanism with
      a trigonal planar metaphosphate intermediate rather than an associative mechanism
      that involves a pentavalent phosphorane intermediate.

PMID- 12044162
TI  - Structural consequences of carboxyamidation of dermaseptin S3.
AB  - Animal-derived antimicrobial peptides are gaining increasing interest for their
      role in the innate immune system and for their potential applications in the
      antimicrobial field. Defining the factors that affect potency and selectivity is
      presently a major challenge to their effective and safe use. Since amidating the
      C-terminal carboxyl is one of the means of enhancing antimicrobial activity, we
      report here our comparative study of the solution structures of the antimicrobial
      peptide dermaseptin S3 and its amidated analogue. Circular dichroism measurements
      suggested that the peptides are basically found in an alpha-helical structure. In
      contrast, NMR measurements revealed the complete absence of alpha-helical
      elements in S3 and a single four-residue helix in the amidated analogue. Whereas
      the native peptide was found to be flexible, containing a hydrogen-bonded turn
      and bends, the amidated analogue exhibited a defined alpha-helix at the C
      terminal region, causing the latter to be significantly elongated and more
      structured. Hence, although the increased potency in amidated antimicrobial
      peptides can be attributed to the increased overall positive charge, in this
      case, amidation has had additional effects beyond modifying the net positive
      charge. It has induced and/or stabilized a helical conformation, causing the
      amidated dermaseptin to be more rigid and more extended than its nonamidated
      analogue. The possible implications on the mode of action are discussed herein.

PMID- 12044163
TI  - Structural studies of metarhodopsin II, the activated form of the G-protein
      coupled receptor, rhodopsin.
AB  - The structural changes that accompany activation of a G-protein coupled receptor
      (GPCR) are not well understood. To better understand the activation of rhodopsin,
      the GPCR responsible for visual transduction, we report studies on the three
      dimensional structure for the activated state of this receptor, metarhodopsin II.
      Differences between the three-dimensional structure of ground state rhodopsin and
      metarhodopsin II, particularly in the cytoplasmic face of the receptor, suggest
      how the receptor is activated to couple with transducin. In particular,
      activation opens a groove on the surface of the receptor that could bind the N
      terminal helix of the G protein, transducin alpha.

PMID- 12044165
TI  - Chromophore organization in the higher-plant photosystem II antenna protein CP26.
AB  - The chlorophyll a/b-xanthophyll-protein CP26 complex belongs to the Lhc protein
      family. It binds nine chlorophylls and two xanthophylls per 26.6 kDa polypeptide.
      Determination of the characteristics of each binding site is needed for the
      understanding of functional organization of individual proteins belonging to the
      photosystem II supramolecular complex. The biochemical and spectroscopic features
      of native CP26 are presented here together with identification of pigment binding
      and energy transitions in different sites. The analysis has been performed via a
      new approach using recombinant CP26 complexes in which the chromophore content
      has been experimentally modified. Data were interpreted on the basis of homology
      with CP29 and LHCII complexes, for which detailed knowledge is available from
      mutation analysis. We propose that one additional Chl b is present in CP26 as
      compared to CP29 and that it is located in site B2. We also found that in CP26
      three chlorophyll binding sites are selective for Chl a, one of them being
      essential for the folding of the pigment-protein complex. Two xanthophyll binding
      sites were identified, one of which (L1) is essential for protein folding and
      specifically binds lutein. The second site (L2) has lower selectivity and can
      bind any of the xanthophyll species present in thylakoids.

PMID- 12044164
TI  - Crystal structure of a four-copper laccase complexed with an arylamine: insights
      into substrate recognition and correlation with kinetics.
AB  - Laccases are multicopper oxidases that catalyze the oxidation of a wide range of
      phenols or arylamines, and their use in industrial oxidative processes is
      increasing. We purified from the white rot fungus Trametes versicolor a laccase
      that exists as five different isozymes, depending on glycosylation. The 2.4 A
      resolution structure of the most abundant isozyme of the glycosylated enzyme was
      solved. The four copper atoms are present, and it is the first crystal structure
      of a laccase in its active form. The crystallized enzyme binds 2,5-xylidine,
      which was used as a laccase inducer in the fungus culture. This arylamine is a
      very weak reducing substrate of the enzyme. The cavity enclosing 2,5-xylidine is
      rather wide, allowing the accommodation of substrates of various sizes. Several
      amino acid residues make hydrophobic interactions with the aromatic ring of the
      ligand. In addition, two charged or polar residues interact with its amino group.
      The first one is an histidine that also coordinates the copper that functions as
      the primary electron acceptor. The second is an aspartate conserved among fungal
      laccases. The purified enzyme can oxidize various hydroxylated compounds of the
      phenylurea family of herbicides that we synthesized. These phenolic substrates
      have better affinities at pH 5 than at pH 3, which could be related to the 2,5
      xylidine binding by the aspartate. This is the first high-resolution structure of
      a multicopper oxidase complexed to a reducing substrate. It provides a model for
      engineering laccases that are either more efficient or with a wider substrate
      specificity.

PMID- 12044166
TI  - Molecular targeting of inhibitor of apoptosis proteins based on small molecule
      mimics of natural binding partners.
AB  - An assay based on a solvent-sensitive fluorogenic dye molecule, badan, is used to
      test the binding affinity of a library of tetrapeptide molecules for the BIR3
      (baculovirus IAP repeat) domain of XIAP (X-linked inhibitor of apoptosis
      protein). The fluorophore is attached to a tetrapeptide, Ala-Val-Pro-Cys-NH(2),
      through a thiol linkage and, upon binding to XIAP, undergoes a solvatochromic
      shift in fluorescence emission. When a molecule (e.g., a natural protein known to
      bind to XIAP or a tetrapeptide mimic) displaces the dye, the emission shifts back
      to the spectrum observed in water. As emission intensity is related to the
      binding of the tetrapeptide, the intensity can be used to determine the
      equilibrium constant, K, for the displacement of the dye by the tetrapeptide. The
      results permit residue-specific analysis of the interaction. Furthermore, we show
      that hydrophobic effects in the fourth position are general and can effectively
      increase overall affinity.

PMID- 12044167
TI  - Distinct structural elements that direct solution aggregation and membrane
      assembly in the channel-forming peptide M2GlyR.
AB  - Restoration of chloride conductance via the introduction of an anion selective
      pore, formed by a channel-forming peptide, has been hypothesized as a novel
      treatment modality for patients with cystic fibrosis (CF). Delivery of these
      peptide sequences to airway cells from an aqueous environment in the absence of
      organic solvents is paramount. New highly soluble COOH- and NH(2)-terminal
      truncated peptides, derived from the second transmembrane segment of the glycine
      receptor alpha-subunit (M2GlyR), were generated, with decreasing numbers of amino
      acid residues. NH(2)-terminal lysyl-adducted truncated peptides with lengths of
      22, 25, and 27 amino acid residues are equally able to stimulate short circuit
      current (I(SC)). Peptides with as few as 16 amino acid residues are able to
      stimulate I(SC), although to a lesser degree. In contrast, COOH-terminal
      truncated peptides show greatly reduced induced I(SC) values for all peptides
      fewer than 27 residues in length and show no measurable activity for peptides
      fewer than 21 residues in length. CD spectra for both the NH(2)- and COOH
      truncated peptides have random structure in aqueous solution, and those sequences
      that stimulated the highest maximal I(SC) are predominantly helical in 40%
      trifluoroethanol. Peptides with a decreased propensity to form helical structures
      in TFE also failed to stimulate I(SC). Palindromic peptide sequences based on
      both the NH(2)- and COOH-terminal halves of M2GlyR were synthesized to test roles
      of the COOH- and NH(2)-terminal halves of the molecule in solution aggregation
      and channel forming ability. On the basis of the study presented here, there are
      distinct, nonoverlapping regions of the M2GlyR sequence that define solution
      aggregation and membrane channel assembly. Peptides that eliminate solution
      aggregation with complete retention of channel forming activity were generated.

PMID- 12044168
TI  - Bundles consisting of extended transmembrane segments of Vpu from HIV-1: computer
      simulations and conductance measurements.
AB  - Part of the genome of the human immunodeficiency virus type 1 (HIV-1) encodes for
      a short membrane protein Vpu, which has a length of 81 amino acids. It has two
      functional roles: (i) to downregulate CD4 and (ii) to support particle release.
      These roles are attributed to two distinct domains of the peptide, the
      cytoplasmic and transmembrane (TM) domains, respectively. It has been suggested
      that the enhanced particle release function is linked to the ion channel activity
      of Vpu, with a slight preference for cations over anions. To allow ion flux
      across the membrane Vpu would be required to assemble in homooligomers to form
      functional water-filled pores. In this study molecular dynamics simulations are
      used to address the role of particular amino acids in 4, 5, and 6 TM helix bundle
      structures. The helices (Vpu(6-33)) are extended to include hydrophilic residues
      such as Glu, Tyr, and Arg (EYR motif). Our simulations indicate that this motif
      destabilizes the bundles at their C-terminal ends. The arginines point into the
      pore to form a positive charged ring that could act as a putative selectivity
      filter. The helices of the bundles adopt slightly higher average tilt angles with
      decreasing number of helices. We also suggest that the helices are kinked.
      Conductance measurements on a peptide (Vpu(1-32)) reconstituted into lipid
      membranes show that the peptide forms ion channels with several conductance
      levels.

PMID- 12044169
TI  - An isotope-edited FT-IR study of a symporter, the lactose permease.
AB  - The lactose permease of Escherichia coli transports protons and lactose across
      the plasma membrane and uses a transmembrane ion gradient as the energy source to
      drive the uphill accumulation of lactose. In this report, the effect of the
      electrochemical gradient on the permease has been studied. Bacteriorhodopsin was
      co-reconstituted with the lactose permease to provide a light-triggered
      electrochemical gradient. Reaction-induced Fourier transform infrared spectra
      were acquired, and bacteriorhodopsin contributions were subtracted. In previous
      work, positive bands in the 1765-1730 cm(-1) region of the reaction-induced FT-IR
      spectrum were attributed to the perturbation of carboxylic acid residues in the
      permease [Patzlaff, J. S., Brooker, R. J., and Barry, B. A. (2000) J. Biol. Chem.
      275, 28695-28700]. In this study, we have globally labeled the permease with
      (13)C or (15)N. Isotopic labeling demonstrates that features in the reaction
      induced FT-IR spectrum arise from permease carboxylic acid, amide I, and amide II
      vibrational modes. In addition, isotope labeling leads to a tentative assignment
      of spectral features to lysine, arginine, histidine, glutamine, and/or asparagine
      in the permease. These results indicate that the electrochemical gradient causes
      changes in the environment or protonation state of carboxylic acid residues in
      the permease and suggest an interaction between these carboxylic acid side chains
      and nitrogen-containing amino acid side chains. Evidence for a change in
      secondary structure, corresponding to an interconversion of secondary structural
      elements, a change in the hydrogen-bonding strength, or coupling of peptide
      vibrational modes, is also presented. These experiments demonstrate the
      usefulness of reaction-induced spectroscopy in the study of transmembrane
      transport.

PMID- 12044170
TI  - Complex of human apolipoprotein C-1 with phospholipid: thermodynamic or kinetic
      stability?
AB  - Thermal unfolding of discoidal complexes of apolipoprotein (apo) C-1 with
      dimyristoyl phosphatidylcholine (DMPC) reveals a novel mechanism of lipoprotein
      stabilization that is based on kinetics rather than thermodynamics. Far-UV CD
      melting curves recorded at several heating/cooling rates from 0.047 to 1.34 K/min
      show hysteresis and scan rate dependence characteristic of slow nonequilibrium
      transitions. At slow heating rates, the apoC-1 unfolding in the complexes starts
      just above 25 degrees C and has an apparent melting temperature T(m)
      approximately 48 +/- 1.5 degrees C, close to T(m) = 51 +/- 1.5 degrees C of free
      protein. Thus, DMPC binding may not substantially increase the low apparent
      thermodynamic stability of apoC-1, DeltaG(25 degrees C) < 2 kcal/mol. The scan
      rate dependence of T(m) and Arrhenius analysis of the kinetic data suggest an
      activation enthalpy E(a) = 25 +/- 5 kcal/mol that provides the major contribution
      to the free energy barrier for the protein unfolding on the disk, DeltaG > or =
      17 kcal/mol. Consequently, apoC-1/DMPC disks are kinetically but not
      thermodynamically stable. To explore the origins of this kinetic stability, we
      utilized dynode voltage measured in CD experiments that shows temperature
      dependent contribution from UV light scattering of apoC-1/DMPC complexes (d
      approximately 20 nm). Correlation of CD and dynode voltage melting curves
      recorded at 222 nm indicates close coupling between protein unfolding and an
      increase in the complex size and/or lamellar structure, suggesting that the
      enthalpic barrier arises from transient disruption of lipid packing interactions
      upon disk-to-vesicle fusion. We hypothesize that a kinetic mechanism may provide
      a general strategy for lipoprotein stabilization that facilitates complex
      stability and compositional variability in the absence of high packing
      specificity.

PMID- 12044171
TI  - Interactions of amyloid beta-protein with various gangliosides in raft-like
      membranes: importance of GM1 ganglioside-bound form as an endogenous seed for
      Alzheimer amyloid.
AB  - GM1 ganglioside-bound amyloid beta-protein (GM1-Abeta), found in brains
      exhibiting early pathological changes of Alzheimer's disease (AD) plaques, has
      been suggested to accelerate amyloid fibril formation by acting as a seed. We
      have previously found using dye-labeled Abeta that Abeta recognizes a GM1
      cluster, the formation of which is facilitated by cholesterol [Kakio, A.,
      Nishimoto, S., Yanagisawa, K., Kozutsumi, Y., and Matsuzaki, K. (2001) J. Biol.
      Chem. 276, 24985-24990]. In this study, we investigated the ganglioside species
      specificity in its potency to induce a conformational change of Abeta, by which
      ganglioside-bound Abeta acts as a seed for Abeta fibrillogenesis, using a major
      ganglioside occurring in brains (GM1, GD1a, GD1b, and GT1b) in raft-like
      membranes composed of cholesterol and sphingomyelin. Abeta recognized ganglioside
      clusters, the density of which increased with the number of sialic acid residues.
      Interestingly, however, mixing of gangliosides inhibited cluster formation. In
      contrast, the affinities of the protein for the clusters were similar
      irrespective of lipid composition and of the order of 10(6) M(-)(1) at 37 degrees
      C. Abeta underwent a conformational transition from an alpha-helix-rich structure
      to a beta-sheet-rich structure with the increase in protein density on the
      membrane. Ganglioside-bound Abeta proteins exhibited seeding abilities for
      amyloid formation. GM1-Abeta exhibited the strongest seeding potential,
      especially under beta-sheet-forming conditions. This study suggested that lipid
      composition including gangliosides and cholesterol strictly controls amyloid
      formation.

PMID- 12044172
TI  - Amyloid-like features of polyglutamine aggregates and their assembly kinetics.
AB  - The repeat length-dependent tendency of the polyglutamine sequences of certain
      proteins to form aggregates may underlie the cytotoxicity of these sequences in
      expanded CAG repeat diseases such as Huntington's disease. We report here a
      number of features of various polyglutamine (polyGln) aggregates and their
      assembly pathways that bear a resemblance to generally recognized defining
      features of amyloid fibrils. PolyGln aggregation kinetics displays concentration
      and length dependence and a lag phase that can be abbreviated by seeding. PolyGln
      aggregates exhibit classical beta-sheet-rich circular dichroism spectra
      consistent with an amyloid-like substructure. The fundamental structural unit of
      all the in vitro aggregates described here is a filament about 3 nm in width,
      resembling the protofibrillar intermediates in amyloid fibril assembly. We
      observed these filamentous structures either as isolated threads, as components
      of ribbonlike sheets, or, rarely, in amyloid-like twisted fibrils. All of the
      polyGln aggregates described here bind thioflavin T and shift its fluorescence
      spectrum. Although all polyGln aggregates tested bind the dye Congo red, only
      aggregates of a relatively long polyGln peptide exhibit Congo red birefringence,
      and this birefringence is only observed in a small portion of these aggregates.
      Remarkably, a monoclonal antibody with high selectivity for a generic amyloid
      fibril conformational epitope is capable of binding polyGln aggregates. Thus,
      polyGln aggregates exhibit most of the characteristic features of amyloid, but
      the twisted fibril structure with Congo red birefringence is not the predominant
      form in the polyGln repeat length range studied here. We also find that polyGln
      peptides exhibit an unusual freezing-dependent aggregation that appears to be
      caused by the freeze concentration of peptide and/or buffer components. This is
      of both fundamental and practical significance. PolyGln aggregation is revealed
      to be a highly specific process consistent with a significant degree of order in
      the molecular structure of the product. This ordered structure, or the assembly
      process leading to it, may be responsible for the cell-specific neuronal
      degeneration observed in Huntington's and other expanded CAG repeat diseases.

PMID- 12044173
TI  - The Mycobacterium leprae hsp65 displays proteolytic activity. Mutagenesis studies
      indicate that the M. leprae hsp65 proteolytic activity is catalytically related
      to the HslVU protease.
AB  - The present study reports, for the first time, that the recombinant hsp65 from
      Mycobacterium leprae (chaperonin 2) displays a proteolytic activity toward
      oligopeptides. The M. leprae hsp65 proteolytic activity revealed a trypsin-like
      specificity toward quenched fluorescence peptides derived from dynorphins. When
      other peptide substrates were used (beta-endorphin, neurotensin, and angiotensin
      I), the predominant peptide bond cleavages also involved basic amino acids in
      P(1), although, to a minor extent, the hydrolysis involving hydrophobic and
      neutral amino acids (G and F) was also observed. The amino acid sequence
      alignment of the M. leprae hsp65 with Escherichia coli HslVU protease suggested
      two putative threonine catalytic groups, one in the N-domain (T(136), K(168), and
      Y(264)) and the other in the C-domain (T(375), K(409), and S(502)). Mutagenesis
      studies showed that the replacement of K(409) by A caused a complete loss of the
      proteolytic activity, whereas the mutation of K(168) to A resulted in a 25% loss.
      These results strongly suggest that the amino acid residues T(375), K(409), and
      S(502) at the C-domain form the catalytic group that carries out the main
      proteolytic activity of the M. leprae hsp65. The possible pathophysiological
      implications of the proteolytic activity of the M. leprae hsp65 are now under
      investigation in our laboratory.

PMID- 12044174
TI  - Site-specific cross-linking of human and bovine hemoglobins differentially alters
      oxygen binding and redox side reactions producing rhombic heme and heme
      degradation.
AB  - Chemically modified human or bovine hemoglobins (Hb) have been developed as
      oxygen-carrying therapeutics and are currently under clinical evaluation.
      Oxidative processes, which are in many cases enhanced when modifications are
      introduced that lower the oxygen affinity, can limit the safety of these
      proteins. We have carried out a systematic evaluation of two modified human Hbs
      (O-R-polyHbA(0) and DBBF-Hb) and one bovine Hb (polyHbBv). We have both measured
      the oxidative products present in the Hb preparations and followed the oxidative
      reactions during 37 degrees C incubations. Autoxidation, the primary oxidative
      reaction which initiates the oxidative cascade, is highly correlated with P(50)
      (R = 0.987; p < 0.002). However, when the results for the other oxidative
      processes are compared, two different classes of oxidative reactions are
      identified. The formation of oxyferrylHb, like the rate of autoxidation,
      increases for all modified Hbs. However, the subsequent reactions, which lead to
      heme damage and eventually heme degradation, are enhanced for the modified human
      Hbs but are actually suppressed for bovine-modified Hbs. The rhombic heme
      measured by electron paramagnetic resonance, which is the initial step that
      causes irreversible damage to the heme, is found to be a reliable measure of the
      stability of ferrylHb and has the tendency to produce degradation products. DBBF
      Hb, a Hb-based oxygen carrier (HBOC) for which toxic side effects have been well
      documented, has the highest level of rhombic heme (41-fold greater than for
      HbA(0)), even though its rate of autoxidation is relatively low. These findings
      establish the importance of these secondary oxidative reactions over autoxidation
      in evaluating the toxicity of HBOCs.

PMID- 12044175
TI  - The synergistic anion-binding sites of human transferrin: chemical and
      physiological effects of site-directed mutagenesis.
AB  - A defining feature of all transferrins is the absolute dependence of iron binding
      on the concomitant binding of a synergistic anion, normally but not necessarily
      carbonate. Acting as a bridging ligand between iron and protein, it completes the
      coordination requirements of iron to lock the essential metal in its binding
      site. To investigate the role of the synergistic anion in the iron-binding and
      iron-donating properties of human transferrin, a bilobal protein with an iron
      binding site in each lobe, we have selectively mutated the anion-binding
      threonine and arginine ligands that form an essential part of the electrostatic
      and hydrogen-bonding network holding the synergistic anion to the protein.
      Preservation of either ligand is sufficient to maintain anion binding, and
      therefore iron binding, in the mutated lobe. Arginine is a stronger ligand than
      threonine, and its loss weakens carbonate and therefore iron binding, but
      maintains the ability of nitrilotriacetate to serve as a carbonate surrogate.
      Replacement of both ligands abolishes anion binding and consequently iron binding
      in the affected lobe. Loss of anion binding in either lobe results in a
      monoferric protein binding iron in normal fashion only in the opposite lobe. Both
      monoferric proteins are capable of transferrin receptor-dependent binding and
      iron donation to K562 cells, but with diminished receptor occupancy by the
      protein bearing iron only in the N-lobe.

PMID- 12044176
TI  - Molecular cloning of the heparin/heparan sulfate delta 4,5 unsaturated
      glycuronidase from Flavobacterium heparinum, its recombinant expression in
      Escherichia coli, and biochemical determination of its unique substrate
      specificity.
AB  - The soil bacterium Flavobacterium heparinum produces several enzymes that degrade
      heparan sulfate glycosaminoglycans (HSGAGs) in a sequence-specific manner. Among
      others, these enzymes include the heparinases and an unusual glycuronidase that
      hydrolyzes the unsaturated Delta4,5 uronic acid at the nonreducing end of
      oligosaccharides resulting from prior heparinase eliminative cleavage. We report
      here the molecular cloning of the Delta4,5 glycuronidase gene from the
      flavobacterial genome and its recombinant expression in Escherichia coli as a
      highly active enzyme. We also report the biochemical and kinetic characterization
      of this enzyme, including an analysis of its substrate specificity. We find that
      the Delta4,5 glycuronidase discriminates on the basis of both the glycosidic
      linkage and the sulfation pattern within its saccharide substrate. In particular,
      we find that the glycuronidase displays a strong preference for 1-->4 linkages,
      making this enzyme specific to heparin/heparan sulfate rather than 1-->3 linked
      glycosaminoglycans such as chondroitin/dermatan sulfate or hyaluronan. Finally,
      we demonstrate the utility of this enzyme in the sequencing of heparinase-derived
      HSGAG oligosaccharides.

PMID- 12044177
TI  - Nitric oxide and peroxynitrite activate the iron regulatory protein-1 of J774A.1
      macrophages by direct disassembly of the Fe-S cluster of cytoplasmic aconitase.
AB  - Posttranscriptional regulation of iron homeostasis involves, among other factors,
      a reversible conversion of the Fe-S enzyme cytoplasmic aconitase to a mRNA
      binding iron regulatory protein (IRP-1) that lacks an Fe-S cluster. Previous
      studies have shown that aconitase/IRP-1 may be a target of *NO or peroxynitrite
      (ONOO(-)), formed after reaction of *NO with superoxide anion (O(2)(*-));
      however, the mechanisms and consequences of such interactions have remained
      uncertain. In this study, recombinant aconitase/IRP-1 was exposed to SIN-1, whose
      thermal decomposition releases *NO and O(2)(*-). Results showed that SIN-1 was
      able to induce concomitant inactivation of aconitase and activation of IRP-1,
      attributable to cluster disassembly induced by ONOO(-). SIN-1 was used also in
      lysates of J774A.1 mouse macrophages grown under control conditions, or subjected
      to iron loading or starvation by treatment with hemin or desferrioxamine,
      respectively. Three lines of evidence confirmed that ONOO(-) activated IRP-1 by
      removing iron from the Fe-S cluster of cytoplasmic aconitase. First, IRP-1
      activation was accompanied by iron release and loss of aconitase activity.
      Second, aconitase activity was recovered by reassembling Fe-S clusters with
      cysteine and ferrous ammonium sulfate. Third, iron release and IRP-1 activation
      were observed in lysates from control or iron-loaded macrophages, containing
      increasing levels of Fe-S clusters, but not in lysates from iron-starved
      macrophages, in which aconitase had already undergone cluster disassembly and
      switched to IRP-1. *NO was less efficient than ONOO(-) in attacking the Fe-S
      cluster of cytoplasmic aconitase; in fact, SIN-1-dependent iron release and IRP-1
      activation were diminished by superoxide dismutase, which scavenged O(2)(*-)
      before it reacted with *NO to form ONOO(-). Under comparable conditions, however,
      both *NO and ONOO(-) inactivated an IRP-2 unable to assemble an Fe-S cluster.
      These results indicate that *NO and ONOO(-) may activate IRP-1 by attacking the
      Fe-S cluster of cytoplasmic aconitase, while also inactivating the cluster
      deficient IRP-2. Such divergent actions offer clues to explain links between iron
      homeostasis and reactive nitrogen species in macrophages involved in inflammation
      or other pathophysiologic conditions.

PMID- 12044178
TI  - Spatial relationship between the prodan site, Trp-214, and Cys-34 residues in
      human serum albumin and loss of structure through incremental unfolding.
AB  - Prodan (6-propionyl-2-(dimethylamino)-naphthalene), a competitive inhibitor of
      warfarin binding to human serum albumin (HSA) at drug site I, was used to
      determine the inter- and intradomain distances of HSA. The fluorescence resonance
      energy transfer (FRET) distances between prodan and Trp-214, prodan and 7
      (diethyl amino)-4-methylcoumarin 3-maleimide (CM)-modified Cys-34, and Trp-214
      and CM-Cys-34 were determined to be 25.5 +/- 0.5 A, 33.1 +/- 0.8 A, and 32.4 +/-
      1 A, respectively. FRET analysis showed that low concentration of palmitic acid
      (5 microM) increased the interdomain distance between the Trp-214 in domain II
      and CM-Cys-34 in domain I by approximately 5 A without perturbing the secondary
      structure of HSA and the immediate environment of Trp-214. Palmitic acid (5
      microM) increased the prodan fluorescence by increasing the quantum yield of
      bound prodan without altering the tryptophan environment. However, palmitic acid
      (>10 microM) decreased the prodan fluorescence and increased the tryptophan
      fluorescence. Our results indicate that the high affinity palmitic acid binding
      site is located at the interface of domains I and II. On the basis of our
      measurements, a schematic model representing the drug site-1, Trp-214, and Cys-34
      along with the palmitic acid sites has been constructed. In addition, prodan
      fluorescence, FRET, and ligand binding were used to monitor guanidine
      hydrochloride-induced denaturation of HSA. An analysis of the equilibrium
      unfolding data suggests that HSA undergoes a two-state unfolding transition with
      no detectable intermediate. However, kinetic analysis using multiple probes and
      thermal denaturation studies showed that the unfolding of the prodan site in HSA
      preceded the unfolding of tryptophan environment. In addition, the separation of
      domain I and II occurred before the global unfolding of the protein. The data
      support the idea that HSA loses its structure incrementally during its unfolding.

PMID- 12044179
TI  - Raman evidence for Meisenheimer complex formation in the hydrolysis reactions of
      4-fluorobenzoyl- and 4-nitrobenzoyl-coenzyme A catalyzed by 4-chlorobenzoyl
      coenzyme A dehalogenase.
AB  - 4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolytic
      dehalogenation of 4-CBA-CoA to 4-hydroxybenzoyl-CoA by using an active site
      Asp145 carboxylate as the nucleophile. Formation of the corresponding
      Meisenheimer complex (EMc) is followed by chloride ion expulsion to form arylated
      enzyme (EAr). The EAr is then hydrolyzed to product. In this paper, we report the
      kinetics for dehalogenase-catalyzed 4-fluorobenzoyl-CoA (4-FBA-CoA) and 4
      nitrobenzoyl-CoA (4-NBA-CoA) hydrolysis and provide Raman spectral evidence for
      the accumulation of EMc in these reactions. The 4-FBA-CoA and 4-NBA-CoA substrate
      analogues were selected for the poor leaving group ability of their C(4)
      substituents. Thus, the formation of the EAr from EMc should be hindered, giving
      rise to a quasi-steady-state equilibrium between EMc and the Michaelis complex.
      Detailed kinetic studies were carried out to quantitate the composition of the
      reaction mixtures. Quench experiments demonstrated that significant populations
      of EAr do not exist in reaction mixtures involving the 4-F- or 4-N-substrates. A
      kinetic model enabled us to estimate that approximately 10-20% of the enzyme
      substrate complexes in the reaction mixtures are present as EMc. Raman difference
      spectra of 4-NBA-CoA and 4-FBA-CoA bound to WT and H90Q mutant dehalogenase have
      broad features near 1500 and 1220 cm(-1) that are absent in the free ligand.
      Crucially, these features are also absent in the Raman spectra of the complexes
      involving the D145A dehalogenase mutant that are unable to form an EMc. Quantum
      mechanical calculations, at the DFT level, provide strong support for assigning
      the novel 1500 and 1220 cm(-1) features to an EMc.

PMID- 12044180
TI  - Catalytic function and local proton structure at the type 2 copper of nitrite
      reductase: the correlation of enzymatic pH dependence, conserved residues, and
      proton hyperfine structure.
AB  - Electron nuclear double resonance (ENDOR) of protons at Type 2 and Type 1 cupric
      active sites correlates with the enzymatic pH dependence, the mutation of nearby
      conserved, nonligating residues, and electron transfer in heterologously
      expressed Rhodobacter sphaeroides nitrite reductase. Wild-type enzyme showed a pH
      6 activity maximum but no kinetic deuterium isotope effect, suggesting protons
      are not transferred in the rate-limiting step of nitrite reduction. However,
      protonatable Asp129 and His287, both located near the Type 2 center, modulated
      enzyme activity. ENDOR of the wild-type Type 2 center at pH 6.0 revealed an
      exchangeable proton with large hyperfine coupling. Dipolar distance estimates
      indicated that this proton was 2.50-2.75 or 2.25-2.45 A from Type 2 copper in the
      presence or absence of nitrite, respectively. This proton may provide a properly
      oriented hydrogen bond to enhance water formation upon nitrite reduction. This
      proton was eliminated at pH 5.0 and showed a diminished coupling at pH 7.5.
      Mutations of Asp129 and His287 reduced enzyme activity and altered the
      exchangeable proton hyperfine spectra. Mutation of Asp129 prevented a pH
      dependent change at the Type 1 Cys167 ligand as observed by Cys C(beta) proton
      ENDOR, implying there is a Type 2 and pH-dependent alteration of the Type 1
      center. Mutation of the Type 1 center ligand Met182 to Thr and mutation of Asp129
      increased the activation energy for nitrite reduction. Involvement of both the
      Type 1 center and Asp129 in modulating activation energy shows that electron
      transfer from the Type 1 center to a nitrite-ligated Type 2 center is rate
      limiting for nitrite reduction. Mutation of Ile289 to Ala and Val caused minor
      perturbation to enzyme activity, but as detected by ENDOR, allowed formate
      binding. Thus, bulky Ile289 may exclude non-nitrite ligands from the Type 2
      active site.

PMID- 12044181
TI  - Redox-coupled proton pumping activity in cytochrome b6f, as evidenced by the pH
      dependence of electron transfer in whole cells of Chlamydomonas reinhardtii.
AB  - The pH dependence of cytochrome b(6)f catalytic activity has been measured in
      whole cells of the green alga Chlamydomonas reinhardtii over the 5-8 range. An
      acid pH slowed the reactions occurring at the lumenal side of the complex
      (cytochrome b(6) and f reduction) and affected also the rate and amplitude of the
      slow electrogenic reaction (phase b), which is supposed to reflect transmembrane
      electron flow in the complex. On the other hand, a direct measurement of the
      transmembrane electron flow from the kinetics of cytochrome b(6) oxidation
      revealed no pH sensitivity. This suggests that a substantial fraction of the
      electrogenicity associated with cytochrome b(6)f catalysis is not due to electron
      transfer in the b(6) hemes but to a plastoquinol-oxidation-triggered charge
      movement, in agreement with previous suggestions that a redox-coupled proton pump
      operates in cytochrome b(6)f complex. The pH dependence of cytochrome b(6)f
      activity has also been measured in two mutant strains, where the glutamic 78 of
      the conserved PEWY sequence of subunit IV has been substituted for a basic (E78K)
      and a polar (E78Q) residue [Zito, F., Finazzi, G., Joliot, P., and Wollman, F.-A.
      (1998) Biochemistry 37, 10395-10403]. Their comparison with the wild type
      revealed that this residue plays an essential role in plastoquinol oxidation at
      low pH, while it is not required for efficient activity at neutral pH. Its
      involvement in gating the redox-coupled proton pumping activity is also shown.

PMID- 12044182
TI  - Conformational changes of the nucleotide site of the plasma membrane Ca2+-ATPase
      probed by fluorescence quenching.
AB  - Fluorescence quenching by the water-soluble ions I(-) and Cs(+) was used to probe
      solvent accessibility and polarity of the nucleotide/fluorescein isothiocyanate
      binding pocket of the purified soluble Ca(2+)-ATPase from plasma membranes. The
      E(1).Ca.CaM conformer was the least accessible state studied, presenting the
      lowest suppression constant (K(q)) for both I(-) (K(q) = 6.7 M(-)(1)) and Cs(+)
      (K(q) = 0.7 M(-)(1)). Accessibility to I(-) was similar for the E(2).VO(4) and
      E(1).Ca states (K(q) = 7.13 and 7.5 M(-)(1), respectively), whereas E(2) was
      slightly more accessible (K(q) = 9.1 M(-)(1)). The phosphorylated state E(2)-P
      presented the highest accessibility, with a K(q) of 16.5 M(-)(1), very near the
      K(q) of 20.3 M(-)(1) for free FITC. I(-) was unequivocally a better fluorescence
      quencher, being usually nearly 3-fold as efficient as Cs(+), as indicated by the
      K(q)(I(-))/K(q)(Cs(+)) ratio (R(q)). The advent of a positive charge cluster on
      the nucleotide/fluorescein binding pocket in different states was suggested by
      the increase in R(q), which reached a value as high as 9.5 for the E(1).Ca.CaM
      conformer. These results indicate (i) a very high water accessibility of the
      nucleotide/fluorescein pocket for E(2)-P that (ii) is more restricted on the free
      E(2) state and (iii) becomes rather lower for the E(1).Ca states. Additionally, a
      positive charge effect of amino acids on the nucleotide site, possibly related to
      ATP binding and phosphoryl transfer, appears in these E(1).Ca states, being
      absent in the phosphorylated and nonphosphorylated E(2) states.

PMID- 12044183
TI  - Functional and structural characterization of a synthetic peptide representing
      the N-terminal domain of prokaryotic pyruvate dehydrogenase.
AB  - A synthetic peptide (Nterm-E1p) is used to characterize the structure and
      function of the N-terminal region (amino acid residues 4-45) of the pyruvate
      dehydrogenase component (E1p) from the pyruvate dehydrogenase multienzyme complex
      (PDHC) from Azotobacter vinelandii. Activity and binding studies established that
      Nterm-E1p specifically competes with E1p for binding to the dihydrolipoyl
      transacetylase component (E2p) of PDHC. Moreover, the experiments show that the N
      terminal region of E1p forms an independent folding domain that functions as a
      binding domain. CD measurements, two-dimensional (2D) (1)H NMR analysis, and
      secondary structure prediction all indicate that Nterm-E1p has a high alpha
      helical content. Here a structural model of the N-terminal domain is proposed.
      The peptide is present in two conformations, the population of which depends on
      the sample conditions. The conformations are designated "unfolded" at pH > or =6
      and "folded" at pH <5. The 2D (1)H TOCSY spectrum of a mixture of folded and
      unfolded Nterm-E1p shows exchange cross-peaks that "link" the folded and unfolded
      state of Nterm-E1p. The rate of exchange between the two species is in the range
      of 0.5-5 s(-1). Sharp resonances in the NMR spectra of wild-type E1p demonstrate
      that this 200 kDa enzyme contains highly flexible regions. The observed dynamic
      character of E1p and of Nterm-E1p is likely required for the binding of the E1p
      dimer to the two different binding sites on E2p. Moreover, the flexibility might
      be essential in sustaining the allosteric properties of the enzyme bound in the
      complex.

PMID- 12044184
TI  - van't Hoff and calorimetric enthalpies II: effects of linked equilibria.
AB  - The complexity of binding reactions, including the linkage with other equilibria,
      is becoming increasingly apparent in biological processes such as signal
      transduction. Understanding these interactions requires obtaining thermodynamic
      profiles for each of the equilibria that occur in a binding event. Concern has
      been raised as to whether linked equilibria contribute differently to
      thermodynamics, such as DeltaH degrees and DeltaC(p), obtained from calorimetric
      and van't Hoff methods. We have previously shown that linked equilibria do not
      contribute differently to the van't Hoff and calorimetrically determined DeltaH
      degrees for processes such as linked folding or hydration. Here, examples of
      proton and ion linkage are examined. We show that there is no reason to expect
      the calorimetric and van't Hoff DeltaH degrees to be different, even without
      prior knowledge of the presence or absence of linked equilibria, as long as the
      system is permitted to equilibrate. However, it is possible to create
      experimental scenarios that result in and discrepancies. Furthermore, it is found
      that the presence of linked equilibria in all cases can result in
      "nonconventional" DeltaH degrees and DeltaC(p) profiles, making data analysis
      nontrivial.

PMID- 12044185
TI  - Peroxynitrite-induced reactions of synthetic oligo 2'-deoxynucleotides and DNA
      containing guanine: formation and stability of a 5-guanidino-4-nitroimidazole
      lesion.
AB  - Peroxynitrite is a strong oxidizing agent that is formed in the reaction of
      nitric oxide and superoxide anion. It is capable of oxidizing and nitrating a
      variety of biological targets including DNA, and these modifications may be
      responsible for a number of pathological conditions and diseases. A recent study
      showed that peroxynitrite reacts with 2',3',5'-tri-O-acetylguanosine to yield a
      novel compound, tri-O-acetyl-1-(beta-D-erythro-pentafuranosyl)-5-guanidino-4
      nitroimidazole, and, unlike other peroxynitrite-mediated guanine oxidation
      products, it is a stable and significant component formed even at low
      peroxynitrite concentrations. In this work, we studied the in vitro formation of
      the guanine-derived product, 5-guanidino-4-nitroimidazole, in synthetic
      oligonucleotides and DNA treated with peroxynitrite. When calf thymus DNA or
      oligonucleotides were reacted with peroxynitrite at ambient temperature, the
      modified base 5-guanidino-4-nitroimidazole was generated along with several other
      products. The oligonucleotides containing the 5-guanidino-4-nitroimidazole
      modification were purified by reverse-phase and anion-exchange HPLC and
      characterized by matrix-assisted laser desorption mass spectrometry. 5-Guanidino
      4-nitroimidazole formation in peroxynitrite-treated DNA was characterized after
      enzymatic digestion of the reacted DNA to the nucleoside level. HPLC purification
      and electrospray ionization mass spectrometry (with selected reaction monitoring)
      enabled the analysis of this modified nucleoside with high sensitivity. The yield
      of 5-guanidino-4-nitroimidazole formed in single-stranded DNA was approximately
      10-fold higher than that found in duplex DNA. With calf thymus DNA, 5-guanidino-4
      nitroimidazole was dose-dependently formed at low peroxynitrite concentrations.
      In stability tests, a synthetic oligonucleotide containing the 5-guanidino-4
      nitroimidazole modification was only partially cleaved by hot piperidine and was
      a weak substrate for Fpg glycosylase repair enzyme; in addition, this site was
      not cleaved by endonuclease III. These results suggest that nuclear DNA
      containing 5-guanidino-4-nitroimidazole may not be quickly repaired by DNA repair
      enzyme systems. Finally, primer extension experiments revealed that this lesion
      is a potential DNA replication blocker when polymerization is catalyzed by
      polymerase alpha and polymerase I (Klenow fragment, lack of exonuclease activity)
      but not with human polymerase beta. Replication fidelity experiments further
      showed that 5-guanidino-4-nitroimidazole may cause G-->T and G-->C transversions
      in calf thymus polymerase alpha and E. coli polymerase I.

PMID- 12044189
TI  - Psychoanalytic contributions to psychiatry.

PMID- 12044186
TI  - Thermodynamics of aminoglycoside and acyl-coenzyme A binding to the Salmonella
      enterica AAC(6')-Iy aminoglycoside N-acetyltransferase.
AB  - Kinetic and mechanistic studies on the chromosomally encoded aminoglycoside 6'-N
      acetyltransferase, AAC(6')-Iy, of Salmonella enterica that confers resistance
      toward aminoglycosides have been previously reported [Magnet et al. (2001)
      Biochemistry 40, 3700-3709]. In the present study, equilibrium binding and the
      thermodynamic parameters of binding of aminoglycosides and acyl-coenzyme A
      derivatives to AAC(6')-Iy and of two mutants, C109A and the C109A/C70A double
      mutant, have been studied using fluorescence spectroscopy and isothermal
      titration calorimetry (ITC). Association constants for different aminoglycosides
      varied greatly (4 x 10(4)-150 x 10(4)) while the association constants of several
      acyl-coenzyme A derivatives were similar (3.2 x 10(4)-4.5 x 10(4)). The
      association constants and van't Hoff enthalpy changes derived from intrinsic
      protein fluorescence changes were in agreement with independently measured values
      from isothermal titration calorimetry studies. Binding of both aminoglycosides
      and acyl-coenzyme A derivatives is strongly enthalpically driven and revealed
      opposing negative entropy changes, resulting in enthalpy-entropy compensation.
      The acetyltransferase exhibited a temperature-dependent binding of tobramycin
      with a negative heat capacity value of 410 cal mol(-1) K(-1). Isothermal
      titration studies of acetyl-coenzyme A and tobramycin binding to mutant forms of
      the enzyme indicated that completely conserved C109 does not play any direct role
      in the binding of either of the substrates, while C70 is directly involved in
      aminoglycoside binding. These results are discussed and compared with previous
      steady-state kinetic studies of the enzyme.

PMID- 12044190
TI  - Psychoanalytic treatments within psychiatry: an expanded view.

PMID- 12044191
TI  - The place of psychoanalytic treatments within psychiatry.

PMID- 12044192
TI  - The place of psychoanalytic treatments within psychiatry.
AB  - Psychoanalytic treatments may be necessary when other treatments are ineffective.
      An empirically grounded framework for the use of these treatments involves
      sources of evidence from both efficacy and effectiveness studies. Preliminary
      evidence suggests that psychoanalysis appears to be consistently helpful to
      patients with milder disorders and somewhat helpful to those with more severe
      disturbances. A greater number of controlled studies are necessary to confirm
      these impressions. A multisite process and outcome study is proposed.

PMID- 12044193
TI  - Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron
      emission tomography and [11C]WAY-100635.
AB  - BACKGROUND: Results of postmortem studies show an elevation in serotonin-1A (5
      hydroxytryptamine-1A [5-HT(1A)]) receptor density in the prefrontal and temporal
      cortices of patients with schizophrenia. This study examined 5-HT(1A) receptors
      in vivo in patients with schizophrenia using positron emission tomography and
      [carbonyl-(11)C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2
      pyridinyl)cyclohexane carboxamide ([(11)C]WAY-100635). METHODS: The 5-HT(1A)
      binding potential of 14 antipsychotic drug-naive patients with a DSM-IV diagnosis
      of schizophrenia was compared with that of 14 age-matched healthy controls.
      Positron emission tomography data were analyzed using 9 cortical regions of
      interest, which were delineated on a coregistered magnetic resonance image and
      transferred to the positron emission tomographic image, with the cerebellum as
      the reference region for a simplified reference tissue model. We also performed a
      voxel-wise comparison using statistical parametric mapping. RESULTS: The region
      of interest-based analysis revealed a significant mean +/- SD cortical 5-HT(1A)
      receptor binding potential increase of 7.1% +/- 6.4% in patients with
      schizophrenia (F = 2.975; P =.02); local differences were +20% in the left medial
      temporal cortex (F = 9.339;P =.005) and +13% in the right medio temporal cortex
      (F = 4.453; P =.045). There were no significant differences in regional tracer
      delivery or cerebellar [(11)C]WAY-100635 uptake. The voxel-based analysis also
      confirmed a group difference in the left medial temporal cortex. CONCLUSIONS: The
      biological significance of elevated 5-HT(1A) receptor density in schizophrenia
      remains unclear. Given the location of 5-HT(1A) receptors on pyramidal cells,
      this elevation may reflect an abnormal glutamatergic network. Our finding needs
      to be viewed in light of preclinical evidence supporting a role for 5-HT(1A)
      receptors in mediating antipsychotic action and extrapyramidal adverse effects of
      drugs.

PMID- 12044194
TI  - Differential hippocampal expression of glutamic acid decarboxylase 65 and 67
      messenger RNA in bipolar disorder and schizophrenia.
AB  - BACKGROUND: Expression of messenger RNA (mRNA) for the gamma-aminobutyric acid
      (GABA)-synthesizing enzyme, glutamic acid decarboxylase (GAD), in the prefrontal
      cortex and the number of GABAergic neurons in the hippocampus are reduced in
      schizophrenia and bipolar disorder. We tested the hypothesis that the expression
      of the 2 isoforms, one 65 kd (GAD(65)) and the other 67 kd (GAD(67)), is
      differentially affected in the hippocampus in schizophrenia and bipolar disorder.
      METHODS: Hippocampal sections from 15 subjects in 3 groups (control subjects and
      subjects with schizophrenia and bipolar disorder) were studied using an in situ
      hybridization protocol with sulfur 35-labeled complementary riboprobes for
      GAD(65) and GAD(67) mRNA. Emulsion-dipped slides were analyzed for the density of
      GAD mRNA-positive neurons in 4 sectors of the hippocampus and for the cellular
      expression level of both GAD mRNAs. RESULTS: The density of GAD(65) and GAD(67)
      mRNA-positive neurons was decreased by 45% and 43%, respectively, in subjects
      with bipolar disorder, but only 14% and 4%, respectively, in subjects with
      schizophrenia. The decreased density of GAD(65) mRNA-positive neurons in subjects
      with bipolar disorder was significant in sectors CA2/3 and dentate gyrus, and
      that of GAD(67) mRNA-positive neurons was significant in CA4, but not other
      hippocampal sectors. Cellular GAD(65) mRNA expression was significantly decreased
      in subjects with bipolar disorder, particularly in CA4, but not in schizophrenic
      subjects. Cellular GAD(67) mRNA expression was normal in both groups. CONCLUSION:
      We have found a region-specific deficit of GAD(65) and GAD(67) mRNA expression in
      bipolar disorder.

PMID- 12044195
TI  - The long-term natural history of the weekly symptomatic status of bipolar I
      disorder.
AB  - BACKGROUND: To our knowledge, this is the first prospective natural history study
      of weekly symptomatic status of patients with bipolar I disorder (BP-I) during
      long-term follow-up. METHODS: Analyses are based on ongoing prospective follow-up
      of 146 patients with Research Diagnostic Criteria BP-I, who entered the National
      Institute of Mental Health (Bethesda, Md) Collaborative Depression Study from
      1978 through 1981. Weekly affective symptom status ratings were analyzed by
      polarity and severity, ranging from asymptomatic, to subthreshold levels, to full
      blown major depression and mania. Percentages of follow-up weeks at each level as
      well as number of shifts in symptom status and polarity during the entire follow
      up period were examined. Finally, 2 new measures of chronicity were evaluated in
      relation to previously identified predictors of chronicity for BP-I. RESULTS:
      Patients with BP-I were symptomatically ill 47.3% of weeks throughout a mean of
      12.8 years of follow-up. Depressive symptoms (31.9% of total follow-up weeks)
      predominated over manic/hypomanic symptoms (8.9% of weeks) or cycling/mixed
      symptoms (5.9% of weeks). Subsyndromal, minor depressive, and hypomanic symptoms
      combined were nearly 3 times more frequent than syndromal-level major depressive
      and manic symptoms (29.9% vs 11.2% of weeks, respectively). Patients with BP-I
      changed symptom status an average of 6 times per year and polarity more than 3
      times per year. Longer intake episodes and those with depression-only or cycling
      polarity predicted greater chronicity during long-term follow-up, as did comorbid
      drug-use disorder. CONCLUSIONS: The longitudinal weekly symptomatic course of BP
      I is chronic. Overall, the symptomatic structure is primarily depressive rather
      than manic, and subsyndromal and minor affective symptoms predominate. Symptom
      severity levels fluctuate, often within the same patient over time. Bipolar I
      disorder is expressed as a dimensional illness featuring the full range
      (spectrum) of affective symptom severity and polarity.

PMID- 12044196
TI  - A national 5-year follow-up of treatment outcomes for cocaine dependence.
AB  - BACKGROUND: Long-term (5-year) outcomes of community treatment for cocaine
      dependence were examined in relation to problem severity at treatment entry and
      treatment exposure throughout the follow-up period. METHODS: Interviews were
      conducted at 1 and 5 years after treatment for 708 subjects (from 45 programs in
      8 cities) who met DSM-III-R criteria for cocaine dependence when admitted to
      treatment in 1991-1993. Primary outcome measures included cocaine use and
      arrests. Self-reported cocaine use showed high overall agreement with urine (79%
      agreement) and hair (80% agreement) toxicology analyses. RESULTS: Weekly cocaine
      use was reported by 25% of the sample at 5 years, slightly higher than the 21% at
      1 year. Similarly, 26% had cocaine detected in urine specimens at follow-up and
      18% reported having been arrested. Poorer long-term outcomes were related to
      higher problem severity at treatment admission and low treatment exposure.
      CONCLUSIONS: The large decreases in cocaine use 1 year after treatment discharge
      were sustained during the 5-year follow-up. Severity of drug and psychosocial
      problems at intake was predictive of long-term outcomes and outcomes improved in
      direct relation to level of treatment exposure.

PMID- 12044197
TI  - Eating disorders during adolescence and the risk for physical and mental
      disorders during early adulthood.
AB  - BACKGROUND: Data from a community-based longitudinal investigation were used to
      investigate whether adolescents with eating disorders are at an elevated risk for
      physical and mental disorders during early adulthood. METHODS: Psychosocial and
      psychiatric interviews were administered to a representative community sample of
      717 adolescents and their mothers from 2 counties in the state of New York in
      1983, 1985 to 1986, and 1991 to 1993. In 1983, the mean age of the youths was
      13.8 years. RESULTS: Adolescents with eating disorders were at a substantially
      elevated risk for anxiety disorders, cardiovascular symptoms, chronic fatigue,
      chronic pain, depressive disorders, limitations in activities due to poor health,
      infectious diseases, insomnia, neurological symptoms, and suicide attempts during
      early adulthood after age, sex, socioeconomic status, co-occurring psychiatric
      disorders, adolescent health problems, body mass index, and worries about health
      during adulthood were controlled statistically. Problems with eating or weight
      during adolescence predicted poor health outcomes during adulthood, regardless of
      whether an eating disorder had been present. Only 22% of the adolescents with
      current eating disorders had received psychiatric treatment within the past year.
      CONCLUSION: Eating disorders during adolescence may be associated with an
      elevated risk for a broad range of physical and mental health problems during
      early adulthood.

PMID- 12044198
TI  - Neurotoxicity, neuroplasticity, and magnetic resonance imaging morphometry: what
      is happening in the schizophrenic brain?

PMID- 12044199
TI  - Antidepressant effects of repetitive transcranial magnetic stimulation in the
      elderly: correlation between effect size and coil-cortex distance.

PMID- 12044200
TI  - Did Ezekiel have temporal lobe epilepsy?

PMID- 12044201
TI  - Chorion type and twin similarity for child psychiatric symptoms.

PMID- 12044202
TI  - Samson was heroic, exhausted, depressed, and in love, but he does not have
      antisocial personality disorder.

PMID- 12044203
TI  - Samson, the bible, and the DSM.

PMID- 12044205
TI  - Rhythmicity in the regulation of luteinizing hormone release.

PMID- 12044206
TI  - Response differences of spontaneous panic and fear.

PMID- 12044207
TI  - The structure of the DSM.

PMID- 12044209
TI  - Atypical antipsychotics and cognition in schizophrenia.

PMID- 12044213
TI  - Domestic violence: the challenge for nursing.
AB  - Domestic violence is a serious public health and human rights concern and an on
      going challenge for nursing. This article provides an overview of the three major
      types of domestic violence: intimate partner abuse, child abuse, elder abuse. The
      scope, history, and health consequences of each type of violence are addressed.
      Despite advances in research, public awareness, legislative initiatives, and
      public policy, these types of interpersonal violence continue to affect millions
      worldwide.

PMID- 12044210
TI  - Improvement of cognitive dysfunction after treatment with second-generation
      antipsychotics.

PMID- 12044214
TI  - Clinical screening and intervention in cases of partner violence.
AB  - Partner violence is a long-term health risk factor that can potentially have far
      reaching, negative consequences on both those abused and their loved ones. The
      term "partner" is used to define opposite and same sex couples who are in
      relationships on a continuum ranging from casually dating to marriage. Partner
      violence includes physical, sexual, psychological, and economic abuse, as well as
      stalking behaviors. Even though the American Medical Association recommends
      screening for partner violence at multiple levels, there are many shortcomings of
      the current screening and intervention practice. Several factors facilitating the
      ineffectiveness of current practice include a lack of information related to the
      prevalence, duration, and severity of partner violence; physician s misguided
      beliefs regarding a victim s desire to disclose; and barriers that the victim
      faces when deciding whether to disclose partner violence. This article addresses
      these shortcomings and identifies nurses as an invaluable resource that has been
      under-utilized for screening and responding to partner violence. Also highlighted
      is one technique know by the acronym "RADAR" that is designed to address issues
      of both screening and intervention. Finally, resources for both health care
      practitioners and victims of abuse are provided.

PMID- 12044215
TI  - Domestic violence and the criminal justice system: an overview.
AB  - It is only recently that domestic violence has been considered a violation of the
      law. Although men have battered, abused and mistreated their wives or intimate
      partners for a long time, historically, wife or partner abuse has been viewed as
      a "normal" part of marriage or intimate relationships. Only towards the end of
      the twentieth century, in the 1970 s, has domestic violence been defined a crime,
      justifying intervention by the criminal justice system. This article surveys the
      history of domestic violence as a criminal offense, and the justice system
      response to woman battering incidents. It first discusses the definition of the
      offense including debates around the offense definition, and the prevalence and
      reported frequency of the behavior termed woman battering. It then reviews the
      legal and social changes over time that have altered the criminal justice system
      s approach to domestic violence. Next it outlines the responses of the police,
      and the prosecution of domestic violence. The article also discusses research
      findings related to domestic violence and the criminal justice system, along with
      current controversies concerning the justice approach to domestic violence, its
      law enforcement, and related unfolding trends in the movement to address domestic
      violence through the criminal justice system.

PMID- 12044216
TI  - Intimate partner violence: implications for nursing.
AB  - Intimate partner violence is responsible for 30% of female homicides in the U. S.
      and has multiple negative health consequences. It is identified as one of the
      objectives in Healthy People 2010. Women are more likely to be assaulted by a
      current or former intimate partner than an acquaintance, family member, friend,
      or stranger. Universal screening is advocated as an effective approach in
      identifying affected women. There exists a few states mandating report of women
      with injuries resulting from IPV but it is only clearly mandated in California.
      Interventions to address the problem include those focused on increasing
      identification and screening, and treatment of intimate partner violence. This
      paper reviews the epidemiology, identification and screening, and interventions
      for IPV. The role for nursing is discussed concluding with directions for further
      investigation.

PMID- 12044217
TI  - Ethical issues in complementary/alternative therapies.

PMID- 12044218
TI  - The Internet as community: communication avenues for health professionals and
      health consumers.

PMID- 12044219
TI  - Intimate partner violence in African American women.
AB  - Violence against African American women, specifically intimate partner abuse, has
      a significant impact on their health and well being. Intimate partner femicide
      and near fatal intimate partner femicide are the major causes of premature death
      and disabling injuries for African American women. Yet, despite this, there is a
      paucity of research and interventions specific and culturally relevant for these
      women. This article focuses on issues relevant to intimate partner violence and
      abuse against African American women by examining existing empirical studies of
      prevalence and health outcomes of intimate partner violence against women in
      general, plus what limited research there is about African American women,
      specifically. It includes a discussion of specific recommendations for research,
      practice, education, and policy to reduce and prevent intimate partner violence
      against African American women.

PMID- 12044221
TI  - Cell separation improves the sensitivity of detecting rare human normal and
      leukemic hematopoietic cells in vivo in NOD/SCID mice.
AB  - BACKGROUND: This report describes a novel cell-separation procedure developed to
      improve detection and analysis of rare human hematopoietic populations, obtained
      from NOD/SCID mice engrafted with normal and/or leukemic stem cells. METHODS: In
      preliminary experiments, artificial mixtures of murine and human BM cells were
      labeled with a combination of Abs specific for murine hematopoietic cells, prior
      to immunomagnetic negative selection using StemSep. In subsequent experiments, BM
      was harvested from individual NOD/SCID mice transplanted 6-12 weeks earlier with
      either human cord blood or primary CML cells and a similar immunomagnetic
      selection procedure was applied to enrich human cells present. RESULTS:
      Application of this selection procedure to mixtures of murine and human
      hematopoietic cells using anti-mouse CD45 and Ter-119 allowed a > 1000-fold
      depletion of murine cells with > 50% recovery of human cells, including
      progenitors. This level of depletion and recovery were found to be reproducible
      for NOD/SCID mice transplanted and engrafted with human cord blood stem cells,
      thus facilitating detection of human progenitors, including colony-forming cells
      (CFC) and LTCIC. For NOD/SCID mice previously transplanted with CML cells, this
      procedure increased the sensitivity of detecting rare human cell subsets by up to
      > 100-fold. This, in turn, improved the sensitivity of RT-PCR for BCR-ABL and
      made possible the identification by FACS of various minor subsets of human cells,
      including CD34(-)CD19/20(+) B-lineage cells, CD34(+) progenitors, mature CD15(+)
      myeloid cells and CD3(+) T cells present in the mice. DISCUSSION: This simple
      cell-depletion procedure should facilitate future investigations of normal and
      CML stem cell populations in vitro and in NOD/SCID mice.

PMID- 12044222
TI  - An analysis of the effect of chronic GvHD on relapse and survival following
      allogeneic PBSC transplantation.
AB  - BACKGROUND: PBSC are increasingly being used as the source of stem cells in
      allogeneic transplantation. An increased incidence of chronic GvHD has been
      suggested following unmanipulated allogeneic PBSC transplantation (PBSCT),
      however, how this affects overall survival is not yet clear. Our aim was to study
      the impact of chronic GvHD on survival and relapse following allogeneic PBSCT.
      METHODS: We have analyzed data from 73 patients undergoing HLA-matched allogeneic
      PBSCT. GvHD prophylaxis was with CYA and MTX in 97% of patients. We have studied
      the incidence of chronic GvHD and its affect on relapse and survival in these
      patients. All patients were at least 100 days post-transplant at the time of
      analysis. RESULTS: Seventy-three patients were evaluable for analysis of chronic
      GvHD. The overall incidence of chronic GvHD was 55% (limited in 18% and extensive
      in 37%). Overall median survival was 991 days, with a 4 year survival rate of
      48%. Twelve patients relapsed. Patients with chronic GvHD had a significantly
      lower incidence of disease relapse (p = 0.005) with a relapse probability of 8%
      at 3 years, compared with 40% in patients with no chronic GvHD. In addition, the
      extent of chronic GvHD had a marked effect on survival, patients with limited
      chronic GvHD had a 4 year survival rate of 83%, compared with 45% in patients
      with extensive chronic GvHD and 38% in patients with no chronic GvHD. This
      difference was primarily due to the low incidence of relapse and low mortality
      seen in patients with limited chronic GvHD. DISCUSSION: The presence and extent
      of chronic GvHD is an important predictor of outcome following allogeneic PBSCT,
      in that patients who developed either limited or extensive chronic GvHD had a low
      risk of disease relapse.

PMID- 12044224
TI  - Umbilical cord blood processing with the Optipress II blood extractor.
AB  - BACKGROUND: We have previously shown that UC blood (UCB) units can be volume
      reduced manually, in a closed system, without major losses of nucleated and
      CD34(+) cells and without the addition of exogenous material. Our aim was to use
      an automated method for the separation of the UCB components using the Optipress
      II, extractor, with the 'buffy-coat' collection in a standardized volume.
      METHODS: After centrifugation, the 51 UCB units were separated into the three
      blood components, plasma, buffy coat (BC) and red cells, using the Optipress II.
      The final volume of the BC fraction, rich in nucleated and progenitor CD34(+)
      cells, was set at 30 mL. The nucleated and CD34(+) cell content of the UCB
      collections and the resulting BC were evaluated. RESULTS: The UCB units were
      grouped according to the volume collected: Group I < 80 mL and Group II > or = 80
      mL. Standardization of the BC at 30 mL resulted in significant volume reduction
      for both groups, with median values of 51% in Group I and 70% in Group II. The
      nucleated and CD34(+) cell recoveries in the BC from Group I were 88% and 99%
      respectively; for Group II they were 80% and 97%. DISCUSSION: This semi-automated
      method of volume reduction efficiently reduces low, as well as high volume UCB
      units, with good nucleated- and progenitor-cell yields. Being a closed system and
      free of external material, the risk of contamination is minimized. The resulting
      fractions are then available for validation studies of the unit, effectively
      fulfilling the main requisites for UCB banking.

PMID- 12044223
TI  - Optimized retroviral transduction protocol for human progenitor cells utilizing
      fibronectin fragments.
AB  - BACKGROUND: Retroviral transduction in the presence of fibronectin (FN) fragments
      has proven an efficient and clinically-applicable procedure for gene transfer
      into hematopoietic cells. So far, FN-based transduction protocols have been
      optimized primarily for transduction of stem cells, whereas for several
      therapeutic applications transduction of clonogenic progenitors (CFU) may be
      sufficient. METHODS: Transduction protocols for CFU were optimized by evaluating
      the effect of growth factors, timing of retroviral transduction, CD34-selection
      and heparin, using a neomycin-phosphotransferase (neo(R))-expressing retroviral
      vector. RESULTS: The presence of multiple growth factors during prestimulation
      and transduction, including the differentiating cytokines G-CSF or GM-CSF,
      substantially enhanced transduction of CFU. Best results were achieved when 24 h
      of prestimulation were followed by a 24-48 h transduction period in the presence
      of the CH-296 FN-fragment and IL-3, IL-11, SCF, erythropoietin (EPO), and GM-CSF.
      With this proto-col we observed highly efficient transduction of BM-derived CFU
      (90.7 +/- 8.8 % G 418-resistant colonies), even with retrovirus preparations of
      moderate infectious titer (5 x 10(4) - 2 x 10(5) CFU/mL). The number of CFU
      increased on average 2.6-fold (range 1.5-3.8) during the transduction procedure.
      Selection of CD34(+) cells prior to transduction did not improve transduction
      efficiency. Heparin, even in concentrations as low as 2.0 microg/mL,
      significantly inhibited transduction of CFU on FN-fragments. DISCUSSION: An
      optimized protocol for retroviral gene transfer into human clonogenic progenitor
      cells that allows highly efficient transduction, even with moderate titer
      retroviral vectors, is presented.

PMID- 12044225
TI  - In vitro and in vivo purging of B lymphoma cells from stem-cell products using
      anti-CD20 Abs.
AB  - BACKGROUND: Autologous stem-cell transplantation has proved curative therapy for
      relapsed NHL. However, recurrence of underlying disease remains the major cause
      of treatment failure in this setting. METHODS: Development of effective MAb
      therapy directed against the B cell surface antigen CD20 has added a valuable
      tool of clearing contaminating lymphoma cells from stem-cell products by either
      in vitro or in vivo application. RESULTS: Transplantation of successfully in
      vitro purged bone marrow using Mabs has been correlated with prolonged survival
      in large Phase-II study. So far, no randomized trial could demonstrate a
      therapeutic benefit for in vitro purging. The anti-CD20 Mab rituximab has been
      used for in vivo purging at the time of stem cell collection or
      peritransplantation. This method has been shown to be safe and feasible. In the
      majority of patients the combination of rituximab with anti-lymphoma chemotherapy
      meant the collected stem cell products were free of molecularly-detectable
      lymphoma cells. DISCUSSION: The increasing ability to kill all lymphoma cells in
      vivo by regimens including myeloablative therapy renders contaminating lymphoma
      cells of the autologous stem cell product the main source for disease recurrence.
      Clearing of these cells remains a prerequisite for curative stem-cell
      transplantation. Establishment of safe and effective therapeutic schedules using
      Mabs will enhance the chance for collection of lymphoma-free hematopoietic stems
      cells.

PMID- 12044226
TI  - Therapeutic uses of MAbs directed against CD20.
AB  - BACKGROUND: There are two main classes of Abs directed against the CD20 Ag that
      have been developed for therapeutic intent: unconjugated and radio-labeled Abs.
      METHODS: The clinical results available from the large clinical trials utilizing
      both the unconjugated and radiolabelled Abs are summarized in this article.
      DISCUSSION: Both of these classes of agents have shown promise in clinical trials
      both alone and in conjunction with conventional chemotherapy or high-dose
      chemotherapy and transplantation. Ongoing research with these agents will provide
      further evidence of the place in clinical practice for these agents.

PMID- 12044228
TI  - CD34(+) immunoselected cells for poor graft function following allogeneic BMT.
AB  - BACKGROUND: Poor graft function without signs of graft rejection following
      allogeneic BMT (allo-BMT) occurs in around 9% of patients. A high incidence of
      hazardous complications may be encountered, leading to life-threatening
      situations. METHODS: We describe three patients who underwent allo-BMT for acute
      leukemia in first complete remission and untreated myelodysplastic syndrome. The
      three patients experienced prolonged and profound granulocytopenia, anemia and
      thrombocytopenia, despite growth factors and transfusions. This was not corrected
      by donor leukocytes infusion. They received a boost of CD34(+) positively
      selected cells from their HLA-identical sibling donors. RESULTS: A rapid
      improvement of peripheral blood cell counts was observed in both patients who
      were in full donor chimerism status at time of boost infusion, whereas the
      patient with mixed chimerism did not show any signs of improvement. Neither
      patient suffered further exacerbation of GvHD. DISCUSSION: Allogeneic positively
      immunoselected CD34(+) cells can represent an interesting alternative treatment
      for poor graft function following allo-BMT, in the absence of graft rejection
      signs.

PMID- 12044230
TI  - Blood and marrow transplantation activities among adult patients in Turkey.
AB  - BACKGROUND: Since 1978, 856 hematopoietic stem-cell transplantations have been
      performed for adult patients in Turkey. METHODS AND RESULTS: Data were collected
      on the source of hematopoietic progenitor cells, recipient diagnosis,
      conditioning regimen, DFS and mortality. The data were analyzed by the national
      registry system of the Blood and Marrow Transplantation Subcommittee of the
      Turkish Society of Hematology. This analysis allowed the examination of national
      trends in survival, outcome and transplant-related complications in certain
      diseases. DISCUSSION: In the allogeneic setting, the results of transplants for
      acute and chronic leukemia, with the exception of severe aplastic anemia, were
      similar to those found in the European and international registries. Likewise, in
      the autologous setting, the transplant results from Turkey paralleled those in
      European and international registries.

PMID- 12044229
TI  - Comparison of three methods of CD34+ cell enumeration in peripheral blood: dual
      platform ISHAGE protocol versus single-platform, versus microvolume fluorimetry.
AB  - BACKGROUND: Quantitation of peripheral blood (PB) CD34(+) cells is now an
      established method for timing PBPC harvesting. Recent refinements to the dual
      platform ISHAGE gating strategy for CD34(+) cells has seen the introduction of
      microbeads to enable absolute counting of cells on a single instrument platform.
      This eliminates the need for total WBCC performed on an automated hematology
      analyzer and potentially increases the analytical precision of the methodology.
      At the same time, alternative methods for CD34(+) cell enumeration have started
      to emerge, notably microvolume fluorimetry, which forms the basis of the fully
      automated STELLer CD34 method using the Imagn 2000. METHODS: We performed a three
      way evaluation of these methods. Sixty-eight samples of PB from 42 patients
      undergoing PBPC mobilization were analyzed by all three methods and correlations
      between all three calculated. The two-platform ISHAGE method was used as the
      reference method. RESULTS: Precision and linearity of the single-platform and
      STELLer CD34 assays were excellent. Correlation with the dual-platform reference
      method was also excellent (single-platform method slope = 1.03, intercept = -0.03
      and R(2) = 0.9325, STELLer CD34 assay slope = 0.827, intercept = 4.27, R(2)
      =0.8215). Bias, determined by Bland-Altman analysis, was 1.16 and -1.62 for
      single platform and STELLer CD34 assay respectively. CONCLUSION: The three
      methods of CD34(+) cell enumeration gave equivalent results. The single-platform
      methodology negated the need for a separate white cell analyzer, while the
      STELLer CD34 methodology was technically the simplest.

PMID- 12044231
TI  - The Argentine experience with autologous and allogeneic stem cell
      transplantation.

PMID- 12044232
TI  - Nonhematopoietic mesenchymal stem cells: what are they?

PMID- 12044233
TI  - Current methods and new developments in graft evaluation.

PMID- 12044234
TI  - Megadose and minitransplantation: what is the biology?

PMID- 12044235
TI  - New approaches to clinical harvest manipulation.

PMID- 12044236
TI  - Stem cell enumeration by flow cytometry: current concepts and recent developments
      in CD34+ cell enumeration.

PMID- 12044237
TI  - Cancer fatigue--more data, less information?

PMID- 12044238
TI  - Soft-tissue sarcoma in childhood and adolescence.
AB  - This review summarizes and comments on the major articles that have been
      published in English concerning pediatric soft-tissue sarcomas in the past 2
      years. Studies of rhabdomyosarcoma and undifferentiated sarcoma, including late
      sequelae of treatment; nonrhabdomyosarcomatous soft-tissue sarcoma; and the
      pathology of soft-tissue sarcomas are included.

PMID- 12044239
TI  - Systemic therapy for advanced soft-tissue sarcomas.
AB  - The field of oncology is experiencing a paradigm shift from broad-spectrum
      cytotoxic therapies to more specific molecularly based targeted therapies. The
      activity of imatinib mesylate in chronic myelogenous leukemia and
      gastrointestinal stromal tumors (GIST) has reinforced our faith in translational
      research and its potential impact on the cure of cancer and improvement in
      quality of life for patients. This breakthrough has been particularly exciting
      for the field of sarcoma and for patients with advanced GIST, for whom no other
      effective therapy was available. Unfortunately, as is becoming increasingly
      clear, cancer is a very complex problem with multiple mechanisms and pathways
      that function either independently or interdependently enabling cell survival. We
      are therefore far away from having solved the problem. Attempts at refining the
      currently available therapeutic armamentarium to maximize the therapeutic index
      (dose intensification with growth factor support) must continue in parallel with
      laboratory-based research identifying critical targets to be inhibited or
      blocked. Identification of new agents with some activity, such as gemcitabine and
      ecteinascidin (ET-743), is also of paramount importance.

PMID- 12044240
TI  - Current therapy for malignant mesothelioma.
AB  - This review briefly summarizes the results of previous systemic (chemotherapy)
      and local (surgery and radiotherapy) treatment attempted to date for malignant
      mesothelioma. The prospects for newer modalities, ie molecular and biologic
      therapies, are also highlighted, including results of both preclinical and early
      clinical research.

PMID- 12044241
TI  - Targeting epidermal growth factor receptor in lung cancer.
AB  - Among the most promising agents in clinical development to treat non-small-cell
      lung cancer (NSCLC) are the epidermal growth factor receptor (EGFR) targeting
      agents. A series of recent studies have demonstrated the activity of anti-EGFR
      targeted therapies for NSCLC. In advanced NSCLC that is refractory to
      chemotherapy, antitumor responses have been reported with EGFR tyrosine kinase
      inhibitors (ZD1839 and OSI-774). The role of ZD1839 and OSI-774 as possible
      additions to standard chemotherapy in the first-line setting has also been
      evaluated, and the studies conducted to date should respond to the question of
      whether these compounds could provide a survival benefit. Other areas of research
      involve looking at the role of EGFR tyrosine kinase inhibitors in the neoadjuvant
      treatment of stage III NSCLC and the planning of chemoprevention studies. These
      exciting results and plans are further complemented by an emerging number of
      compounds in clinical development, including both monoclonal antibodies (ie, IMC
      C225) and other tyrosine kinase inhibitors, directed at the EGFR.

PMID- 12044243
TI  - p53 Gene therapy for lung cancer.
AB  - The gene transfer of the tumor suppressor p53 gene has been shown to induce tumor
      regression in preclinical models. Recent phase I and II studies have been
      completed in lung cancer with adenoviral-mediated transfer of wild-type p53 (Ad
      p53) either alone or in combination with chemotherapy or radiotherapy. These
      studies have demonstrated acceptable toxicity and evidence of tumor regression
      with intratumoral delivery of Ad-p53. The predominant clinical effect appears to
      be locoregional in the area of intratumoral delivery. Further phase III studies
      are needed to determine if Ad-p53 will play a therapeutic role as a novel agent
      to treat non-small-cell lung cancer.

PMID- 12044242
TI  - Angiogenesis inhibitors in lung cancer.
AB  - Lung cancer is a major public health problem and the leading cause of cancer
      related death worldwide. Its survival rates have changed little over the past 20
      years. The best clinical benefit (ie, survival rates) with combination cytotoxic
      therapies in non-small-cell lung cancer (NSCLC) may have been reached. The need
      for improved survival rates in NSCLC has driven the development of novel,
      rationally designed, targeted therapies. Inhibitors of angiogenesis have been
      developed and are increasingly studied. Potential targets for therapy include
      inhibitors of vascular endothelial growth factor receptor, endogenous
      angiogenesis inhibitors, and cyclooxygenase inhibitors. Combining targeted
      molecules with traditional cytotoxic therapies usually results in lower required
      chemotherapy doses and fewer, less severe side effects. A number of ongoing
      randomized studies are underway to evaluate this idea. It is anticipated that
      these new targeted therapies will play an important role, along with cytotoxic
      and radiation therapies, in the management of metastatic disease.

PMID- 12044245
TI  - Three-dimensional conformal radiotherapy for lung cancer: promises and pitfalls.
AB  - Lung cancer represents a major source of morbidity and mortality. Despite recent
      advances, long-term survival remains elusive in most patients with locally
      advanced cancer. A substantial proportion of these patients experience a relapse
      at the original site of disease within the thorax, making radiotherapy an
      important component of treatment. Of several approaches investigated to improve
      the therapeutic ratio in radiotherapy, three-dimensional conformal radiotherapy
      holds the most promise, primarily because it allows higher doses to be delivered
      to the target by improved shaping of radiation portals and conformal avoidance of
      normal structures. The rationale and evolution of this technology and its
      potential pitfalls are presented in this review.

PMID- 12044246
TI  - Current surgical management of malignant pleural mesothelioma.
AB  - Malignant pleural mesothelioma is a rare and very aggressive malignancy with an
      increasing incidence. Single-modality therapy has failed to improve median
      survival. Current surgical therapies include palliative and cytoreductive
      procedures. The rarity of the disease, the lack of randomized surgical studies,
      and the lack of a universally accepted and validated staging system make it
      difficult to reach consensus and establish stage-specific protocols. However,
      with strict criteria, subsets of patients can be identified who can benefit from
      aggressive cytoreductive surgical approaches, such as extrapleural pneumonectomy,
      and adjuvant chemoradiation protocols. Our experience with this type of protocol
      in carefully selected patients has resulted in increased median survival. The
      lack of cure in any of the published protocols demonstrates the need for new
      therapies and approaches for this disease.

PMID- 12044244
TI  - Chemoprevention of lung cancer.
AB  - Lung cancer is the leading cause of death worldwide. Its overall survival rate
      has improved only slightly, and surgery, radiotherapy, and chemotherapy remain
      the mainstays of current treatment. Therapies with novel targeted agents are
      currently under active investigation in all settings of treatment including
      chemoprevention, defined as the use of natural or synthetic agents to interrupt
      the process of carcinogenesis and to prevent or delay tumor occurrence. Thus,
      chemoprevention describes the collaborative efforts of researchers in basic
      science and clinical settings who study the biology of lung cancer with the hope
      of uncovering new mechanisms of treatment. Because lung cancer has become an
      increasingly difficult problem to treat with standard therapies, chemopreventive
      strategies have been developed. Small molecule compounds that target specific
      receptors or mutations will play an increasingly significant role in treatment of
      lung cancer because the side effect profiles of such agents are tolerable and
      they may be more effective than other treatments.

PMID- 12044247
TI  - Nonrecognition of depression in Parkinson's disease.

PMID- 12044248
TI  - Significance of the parkin gene and protein in understanding Parkinson's disease.
AB  - Mutations in the parkin gene cause autosomal recessive inherited juvenile
      parkinsonism (ARJP) and account for the majority of cases of inherited
      Parkinson's disease (PD) of young onset (<45 years of age). Patients with parkin
      mutations commonly have atypical clinical features such as dystonia at onset,
      hyper-reflexia, diurnal fluctuations, and sleep benefit; however, parkin mutation
      patients with both typical PD symptoms and older age of onset have been
      identified. Parkin is a ubiquitin protein ligase (E3), a component in the pathway
      that attaches ubiquitin to specific proteins, designating them for degradation by
      the proteasome. Several substrates for parkin have been identified (CDCrel-1, o
      glycosylated alpha-synuclein, parkin associated endothelin-like cell receptor,
      and synphilin). The role of these substrates in the pathogenesis of ARJP is under
      active study. Most patients with parkin mutations lack Lewy bodies, suggesting
      that functional parkin is involved in the formation of these highly ubiquitinated
      inclusions. Furthermore, the recognition that parkin mutations can lead to a
      disorder clinically similar to sporadic PD, but presumably lacking Lewy bodies,
      calls into question the necessity of Lewy bodies for the diagnosis of PD and
      nigral cell death. Studies of parkin are increasing the focus on the role of the
      ubiquitin-proteasome system in the pathogenesis of both familial and sporadic PD.

PMID- 12044249
TI  - Psychiatric symptoms in Parkinson's disease.
AB  - Aside from the well-known triad of resting tremor, postural instability, and
      bradykinesia, Parkinson's disease (PD) patients may also develop psychiatric
      illness as a part of their disease. The psychiatric symptoms may be as disabling
      as the movement disorder, but are often amenable to treatment. We review the most
      recent investigations of mood disorders, anxiety disorders, and hallucinations/
      psychosis in PD. We then highlight new treatment studies for
      hallucinations/psychosis in PD.

PMID- 12044250
TI  - Parkinson's disease: medical treatment of moderate to advanced disease.
AB  - Parkinson's disease, a common neurodegenerative disorder, results in significant
      morbidity 10 to 15 years after disease onset and increased mortality. Levodopa is
      the mainstay of therapy and provides benefit for the duration of the illness.
      However, within 5 years, up to 50% of individuals develop fluctuations, including
      dyskinesias, wearing off, and "on/off" effects. Optimal management of Parkinson's
      disease patients requires careful titration of medications, with use of
      polypharmacy, including levodopa, dopamine agonists, catechol-O-methyltransferase
      inhibitors, amantadine, and anticholinergics in order to maintain good motor
      function and quality of life. With advancing disease, problems such as dysphagia,
      dysarthria, and gait and balance abnormalities occur, which are not responsive to
      dopaminergic medication. Due to extradopaminergic neuronal system degeneration,
      autonomic dysfunction can also be prominent. Recognition and management of these
      problems is helpful in improving quality of life in late-stage disease. In very
      late stages, dementia may complicate treatment, requiring discontinuation of
      combination therapy and use of low-dose levodopa with atypical neuroleptics.

PMID- 12044251
TI  - Diagnosis and treatment of Wilson's disease.
AB  - Wilson's disease (WD) is an autosomal recessive disease that causes increased
      copper deposition in the liver and basal ganglia with resultant hepatic and
      neurologic sequelae. In the past few years, dramatic new discoveries have changed
      our understanding of the pathophysiology of WD. Although there are potentially
      life-saving therapies for WD, there is much controversy surrounding the optimal
      treatments of patients in the various stages of the disease. Specifically, the
      relative roles of penicillamine, trientene, and tetrathiomolybdate in the initial
      treatment of the symptomatic patient with WD remain to be defined. Zinc
      monotherapy for maintenance treatment and in the treatment of asymptomatic
      patients with WD is still controversial. It is also unclear whether neurologic
      status alone is an indication for liver transplantation in WD. This paper reviews
      the pathogenesis, genetics, clinical presentation, and diagnosis, with a special
      emphasis on the treatment controversies that arise in the care of the WD patient.

PMID- 12044253
TI  - Spinocerebellar degenerations: an update.
AB  - Over the past decade, the spinocerebellar degenerations have gone from a diverse
      group of loosely defined phenotypes to a family of diseases with many
      identifiable genotypes and the promise of gene-specific treatments. The
      evaluation of the spinocerebellar ataxias has been simplified, and the counseling
      of patients and families has been enhanced by the growing number of molecular
      diagnostic tests now available. Management strategies remain symptomatic and
      focused on rehabilitation, with empirical use of antioxidants based on research
      in other neurogenetic diseases.

PMID- 12044252
TI  - Management of essential tremor.
AB  - Essential tremor (ET) is the most prevalent tremor syndrome. It commonly affects
      the hands, head, voice, and other body parts. Appropriate management begins with
      correct diagnosis. Primidone and propranolol are the first-line medications for
      the treatment for ET, but several other medications may also provide benefit. In
      patients with medically refractory tremor, alternative therapies, including
      surgery or injections of botulinum toxin, may be considered.

PMID- 12044254
TI  - The current state of treatment of status epilepticus.
AB  - There have been many important developments in the diagnosis and treatment of
      status epilepticus in the recent past. Earlier treatment, including at home by
      caregivers and in the field by paramedics, has been shown to be safe and
      effective. Rapid-acting anesthetic agents, such as midazolam and propofol, are
      being used more often for refractory status epilepticus, though clinical trials
      are lacking. Nonconvulsive status epilepticus is being considered and recognized
      more often, including in ambulatory patients with a confusional state, after
      convulsive status epilepticus, and in critically ill patients. Modern technology
      and continuous digital electroencephalogram (EEG) recordings have taught us many
      things, but have raised at least as many questions. Much work needs to be done
      regarding the significance of certain EEG patterns (particularly periodic
      discharges) and when and how to treat them. This article reviews these issues,
      concentrating on recent advances and practical issues related to the clinical
      care of patients with status epilepticus.

PMID- 12044255
TI  - Neurostimulation therapy for epilepsy.
AB  - Neurostimulation therapy for epilepsy is growing in popularity. By appropriate
      targeting of applied electrical activation at selected nervous system sites,
      antiseizure effects may be achieved without the common sedative side effects of
      antiepileptic medications. Risks of neurostimulation therapy are those associated
      with the device implantation surgical procedures. Vagus nerve stimulation (VNS)
      reduces seizures by 45% and has been employed in over 13,000 patients worldwide.
      New reports suggest VNS is particularly beneficial for patients with Lennox
      Gastuat syndome. VNS also reduces sudden unexpected death in epilepsy. New
      publications describing small, uncontrolled case series also suggest deep brain
      stimulation and transcranial magnetic stimulation may develop into effective
      antiepileptic therapies in the future.

PMID- 12044256
TI  - Neuropsychiatric complications of epilepsy.
AB  - Psychiatric complications of epilepsy are multiple and result from the complex
      interaction between endogenous, genetic, therapeutic, and environmental factors.
      The relationship between epilepsy and psychiatric disorders may be much closer
      than previously appreciated. Recent studies have suggested the existence of a bi
      directional relationship between depression and epilepsy, whereby patients with
      epilepsy have a higher risk than the general population of suffering from
      depression, not only after, but also before the onset of epilepsy. Furthermore,
      similar neurotransmitter changes have been identified in depression and epilepsy,
      suggesting the possibility that these two disorders share common pathogenic
      mechanisms. Although the clinical manifestations of psychiatric disorders in
      epilepsy are often indistinguishable from those of nonepileptic patients, certain
      types of depression and psychotic disorders may present with clinical
      characteristics that are particular to epilepsy patients. These include the
      psychosis of epilepsy, postictal psychotic disorders, alternative psychosis (or
      forced normalization), and certain forms of interictal depressive disorders.

PMID- 12044259
TI  - Tacrolimus ointment compared with hydrocortisone acetate in children, and
      hydrocortisone butyrate in adults.

PMID- 12044258
TI  - Chronic urticaria--new concepts regarding pathogenesis and treatment.

PMID- 12044257
TI  - Neurodevelopmental effects of antiepileptic drugs.
AB  - Although the vast majority of children born to women with epilepsy are normal,
      these children are at increased risk for both anatomic and cognitive impairments.
      Current evidence suggests that the defects are the result of in utero
      antiepileptic drug (AED) exposure combined with a genetic predispositon. However,
      the exact mechanisms underlying these effects remain to be delineated. AED
      polytherapy increases the risk, but it remains uncertain if specific AEDs pose an
      overall greater threat. Most women with epilepsy cannot avoid AEDs during
      pregnancy because of the greater risks posed by seizures to the mother and fetus.
      Therefore, current recommendations emphasize definitive diagnosis and the use of
      AED monotherapy at the lowest effective dose if treatment is indicated. Prenatal
      folate and multivitamins should also be given routinely to women of childbearing
      age who require AED therapy.

PMID- 12044260
TI  - The relationship between HIV infection and atopic dermatitis.
AB  - Patients with HIV infection exhibit a wide range of skin pathology, including
      bacterial, fungal, and viral infections, skin tumors, inflammatory and eczematous
      eruptions, and drug rashes. HIV-infected adults commonly develop a condition that
      strongly resembles atopic dermatitis and is sometimes called "atopic-like
      dermatitis"; moreover, atopic dermatitis and other atopic disorders have been
      described as common manifestations of pediatric HIV infection. Conditions such as
      sinusitis, asthma, and hyper-IgE syndrome, and laboratory abnormalities, eg,
      elevated IgE levels, eosinophilia, and possible Th1-Th2 imbalances, suggest a
      predilection for atopic disorders in these patients. It is of interest to examine
      the immune perturbations intrinsic to HIV infection, and their possible role in
      triggering atopic dermatitis, and to consider whether other abnormalities, such
      as xerosis, bacterial or viral superantigens, or epidermal barrier disruption
      with altered presentation of cutaneous aeroallergens, might play a significant
      role.

PMID- 12044262
TI  - Late-phase urticaria Update.
AB  - In ordinary urticaria, individual lesions disappear within 24 hours. However, we
      sometimes encounter patients whose eruptions last longer than 24 hours, but
      without evidence of vasculitis or a history of exposure to pressure. In these
      patients, histology reveals a perivascular infiltration, predominantly of
      eosinophils, depending on the timing of the biopsy. Unlike urticarial vasculitis,
      no immunoglobulins, complement deposition, or endothelial fibrinoid degeneration
      is observed. The peripheral eosinophil counts and serum complement levels appear
      within normal range. No protein urea or joint pain is observed, and the lesions
      can be controlled only by systemic glucocorticoids. We recognize such a
      urticarial reaction as a different clinical entity than usual urticaria, which is
      presumably mediated by late-phase inflammatory reaction in immediate
      hypersensitivity.

PMID- 12044261
TI  - Skin manifestations of drug reactions.
AB  - Dermatologic manifestations of adverse drug reactions are commonly encountered in
      both hospital-based and ambulatory medical practice. Diagnosis is confounded by
      the myriad clinical presentations associated with cutaneous drug eruptions. Some
      presentations are highly characteristic, while others are not as straightforward,
      and may simulate other primary dermatoses. In many cases, patients are utilizing
      several medications and an obvious temporal relationship to a specific drug is
      not always apparent or expressed by the patient during disclosure of his or her
      medical history. A thorough medication history and a high index of suspicion are
      very important components in the diagnosis of drug eruptions.

PMID- 12044263
TI  - Effect of early or delayed insertion of tympanostomy tubes.

PMID- 12044264
TI  - Otitis media: diagnosis, management, and judicious use of antibiotics.
AB  - Otitis media continues to present a major challenge to practitioners in the
      clinical setting. With the ever-increasing trend toward the use of a sound
      research-structured approach to health care and the use of evidence-based
      guidelines, it is important to have an understanding of these findings related to
      otitis media. A review of research-supported literature regarding the diagnosis
      and management of this disease, and suggestions for the judicious use of
      antibiotics, are presented in this paper.

PMID- 12044265
TI  - The genetics of otitis media.
AB  - Almost every child will suffer at least one episode of otitis media (OM).
      Therefore, it is not immediately obvious that there is a genetic predisposition
      to the development of the disease. However, evidence from a variety of studies
      has shown that there is a clear genetic component to susceptibility to OM.
      Methodologies for discovering these genes are described within this article. The
      identification of OM susceptibility genes allows the development of molecular
      diagnostic assays that will inform the clinician as to which child is at
      increased risk and warrants more aggressive intervention. Delineating the OM
      genes not only provides a deeper understanding of the pathophysiology of this
      common disease, but also of acute and chronic bacterial disease in general.

PMID- 12044267
TI  - Nedocromil sodium and levocabastine.

PMID- 12044266
TI  - Immunologic aspects of otitis media.
AB  - The middle ear cleft is a modified gas pocket which functions normally when the
      gas contents are regulated by a normal eustachian tube, resulting in equalization
      of middle ear pressure to that of the environment. The most important regulator
      of this middle ear pressure is the eustachian tube, a critical passageway from
      the nasopharynx into the middle ear. Any alteration of eustachian tube
      mucociliary function caused by virus, allergy, pollutants, or alteration of the
      normal homeostasis of the nasopharynx will result in eustachian tube obstruction.
      This, in turn, leads to underventilation of the middle ear, and transudation of
      fluid. If bacteria or virus or viral-bacterial interaction leads to infectious
      disease of the middle ear, an immune response is produced as a result of the
      inflammatory response, allowing lymphocytes and antigen-presenting cells to enter
      into the middle-ear mucosa. This article summarizes the immunologic reactivity in
      the middle ear following a viral-bacterial inflammatory reaction in the middle
      ear mucosa. Although secretory IgA is critical for protection of the nasopharynx,
      its function in the middle ear has still not been resolved. The evidence strongly
      suggests that IgG1 and IgG3 subclasses are responsible for eradication of middle
      ear pathogens. Finally, a review of alternative approaches to the prevention of
      otitis media is briefly discussed in this critical period of emergence of
      resistant bacteria to available antibiotics.

PMID- 12044268
TI  - The clinical spectrum of ocular allergy.
AB  - Ocular allergy is a very common pathology, and its incidence has increased in
      industrial countries in combination with an increase in atopy. Many different
      clinical features characterize the ocular allergy, which can be seasonal,
      perennial, or chronic. Therefore, ocular allergy must be considered part of the
      allergic syndrome; perennial or seasonal keratoconjunctivitis appear to be
      directly related to allergic rhinitis manifestations and, less frequently, to
      asthma and eczema. The principal field of research in ocular allergy concerns
      therapeutic applications and new concepts of physiopathologic mechanisms needed
      to understand the most optimal treatment that can be delivered.

PMID- 12044269
TI  - The central role of conjunctival mast cells in the pathogenesis of ocular
      allergy.
AB  - Ocular allergic diseases are characterized by specific activation of conjunctival
      mast cells with subsequent release of preformed and newly formed mediators. Mast
      cell numbers on the ocular surface are increased in all forms of allergic
      conjunctivitis. Mast-cell activation plays a central role in the development of
      the ocular allergic reaction, which can be divided into an early and a late
      inflammatory phase. Mast-cell mediators have been measured in tears of patients
      suffering from various forms of allergic conjunctivitis, and in sensitized
      patients after specific ocular allergen challenge. Histamine and tryptase are the
      most studied mediators in tears of allergic patients. Several cytokines, such as
      IL-4 and TNF-a, are also produced and released by conjunctival mast cells, and
      probably play a role in the immunoregulation on the ocular surface. In vitro
      studies of the characteristics and biologic functions of conjunctival mast cells
      highlight their central role in the pathogenesis of ocular allergy, and have led
      to new opportunities to evaluate anti-allergic compounds. This review discusses
      the role of conjunctival mast cells in the development of ocular allergic
      diseases.

PMID- 12044271
TI  - Travel insurance claims made by travelers from Australia.
AB  - BACKGROUND: Little is known about travel insurance claims made by travelers
      returning from abroad. This study was designed to investigate travel insurance
      claims made by travelers from Australia, particularly examining demographic
      factors, type of travel insurance coverage, nature and duration of travel, when
      treatment was sought during travel or when the problem arose, use of emergency
      assistance, nature of claim, and claim outcome, including cost. METHODS: A random
      sample of approximately one in five claims reported during the period 1996 to
      1998 to a major Australian travel insurance company were examined. RESULTS: A
      total of 855 claims were examined, of which 42.6% (356/836) were made by male
      travelers and 57.1% (477/836) were made by female travelers. The majority of
      claimants were in the 55 years and over age groups (445/836, 53.2%). Medical and
      dental conditions accounted for 66.6% of claims (569/854), with the remainder
      associated with loss, theft, and damage (285/854, 33.4%). The most common medical
      conditions were respiratory (110/539, 20.4%), musculoskeletal (90/539, 16.7%),
      gastrointestinal (75/539, 13.9%), ear, nose, and throat (67/539, 12.4%), and
      dental conditions (39/539, 7.2%). Only one case of venous thrombosis was
      reported, secondary to a lower limb infection. Use of the travel insurance
      company's emergency telephone service was reported in 17.1% of claims (146/853).
      Almost two-thirds (559/853, 65.5%) of claims were fully accepted. Those who
      claimed medical treatment, assault, and theft were significantly more likely to
      have their claims accepted compared to those claiming dental conditions,
      cancellation, curtailment, loss and damage (chi2 = 127.78, df = 40, p <.00001).
      The majority of medical and dental conditions did not require further medical
      investigations (427/569, 75.0%). The mean cost of claim refunds was Australian
      dollars (AUD)991.31 (standard deviation [SD] 6 AUD5400.76) for males and
      AUD508.90 (SD 6 AUD1446.10) for females. Claims for assault, cancellation, and
      curtailment were significantly more expensive than other types of claims (Kruskal
      Wallis one way analysis of variance [ANOVA]; chi2 = 106.87, df = 8, p <.00001).
      Claims for treatment of gastrointestinal, cerebrovascular, cardiovascular,
      musculoskeletal conditions, and pyrexias of unknown origin were significantly
      more expensive than other medical and dental claims (Kruskal-Wallis one way
      ANOVA; x2 = 61.68, df = 15, p <.00001). CONCLUSIONS: This explorative study
      highlights the importance of travelers taking out appropriate travel insurance.
      Claims for medical and dental conditions represent the majority of travel
      insurance claims made by Australian travelers returning from abroad, although
      travel insurance also covers against such contingencies as loss, theft, and
      cancellation. The most common medical conditions claimed were respiratory,
      musculoskeletal, and gastrointestinal disorders. Travelers should be advised to
      take out appropriate travel insurance before departure overseas and to take care
      with preexisting medical and dental conditions, which may not be able to be
      claimed against travel insurance.

PMID- 12044270
TI  - Pathophysiology of ocular allergy: the roles of conjunctival mast cells and
      epithelial cells.
AB  - Allergic eye disease is associated with IgE-mediated conjunctival inflammation
      leading to signs of immediate hypersensitivity, including redness, itching, and
      tearing. Pathologic studies using conjunctival mast cells demonstrate that these
      cells, when sensitized with IgE antibody and exposed to environmental allergens,
      release mediators involved with allergic inflammation. The type, release
      kinetics, and concentration of these mediators in the conjunctiva have not been
      completely characterized. The ability to isolate and purify mast cells and
      epithelial cells from human conjunctival tissue has permitted the study of
      mediator release and cell-to-cell signaling in this tissue. Our laboratory has
      developed in vitro and in vivo models to better understand how inflammatory cells
      are recruited to and infiltrate conjunctival tissues. These models demonstrate
      that mast-cell activation may supply sufficient cytokine signaling to initiate
      and direct the well-orchestrated trafficking of eosinophils to the ocular
      surface, facilitate their adhesion, and cause release of potent mediators of
      ocular inflammation.

PMID- 12044273
TI  - Empiric immunization versus serologic screening: developing a cost-effective
      strategy for the use of hepatitis A immunization in travelers.
AB  - BACKGROUND: Older individuals and those born overseas are thought at increased
      risk of prior exposure and thus have naturally acquired immunity to hepatitis A.
      Whether these individuals or other groups of international travelers should be
      screened for acquired immunity or empirically immunized is not clear. Hepatitis A
      serology and risk factor data was obtained prospectively in patients presenting
      for hepatitis A immunization and used to develop a cost-effective strategy for
      the use of serologic screening and empiric immunization in our traveler
      population. METHOD: Candidates for hepatitis A immunization were routinely
      screened for total hepatitis A serum antibody. Risk factor data including country
      of birth, travel history, and history of jaundice was collected. Cost
      effectiveness was assessed by comparing the cost of serology to screen all
      patients plus cost to immunize those found to be seronegative with, the cost of
      empirically immunizing all patients. RESULTS: Analyses were conducted comparing
      age, travel history, country of birth, and history of jaundice for significance
      in predicting seropositivity in a group of 115 subjects. Country of birth was
      statistically a significant predictor of positive results with 80.0% of foreign
      born patients positive for total antibody against hepatitis A compared with 35.6%
      of patients born in the United States. Living outside of the United States
      (defined as greater than 30 days) was also correlated with a higher prevalence of
      hepatitis A positive serology. Age was not predictive for the group as a whole. A
      lower prevalence (24.3%) was noted in the group of US born individuals aged 30 to
      60. Travel and prior history of jaundice failed to demonstrate significance.
      CONCLUSIONS: Employing a simple cost-effectiveness equation using cost of
      serological testing, cost of vaccine, and prevalence of acquired immunity in the
      community, a strategy was developed. In our population it was cost-effective to
      screen all foreign-born individuals and those who had lived outside the United
      States.

PMID- 12044272
TI  - An open randomized study of inactivated hepatitis A vaccine administered
      concomitantly with typhoid fever and yellow fever vaccines.
AB  - BACKGROUND: Concomitant administration of several vaccines is a common practice
      when travel clinics prepare persons for international travel. The purpose of the
      study was to compare the immunogenicity and safety of hepatitis A, typhoid fever,
      and yellow fever vaccines administered concomitantly with hepatitis A vaccine
      administered alone and typhoid fever and yellow fever vaccines administered
      alone. METHODS: Healthy adults 18 to 55 years of age were randomized to receive
      either VAQTA, TyphimVi, and YF-VAX on day 0 and VAQTA at week 24 (Group 1);
      TyphimVi and YF-VAX on day 0 and an optional dose of VAQTA 1 month later (Group
      2); or VAQTA at day 0 and week 24 (Group 3). RESULTS: From March to December
      1997, a total of 240 subjects were enrolled, 80 in each treatment group. Most
      were female and Caucasian, and the mean age was 29.4 years. Four weeks after
      vaccine dose 1, seroconversion to protective antibody levels against hepatitis A
      was 95.9% in Group 1 and 100% in Group 3. In Group 1, 93.4% of subjects
      demonstrated at least a 4-fold rise in neutralizing antibody levels against
      typhoid, compared with 90% in Group 2. Serum neutralizing antibody against yellow
      fever developed in 98.6% of subjects in Group 1 compared with 100% in Group 2.
      CONCLUSIONS: These findings were consistent with similarity in the immune
      responses between treatment groups as defined a priori. The adverse experience
      (AE) profile did not appear to be substantially affected by concomitant
      administration of all three vaccines. Providing these three vaccines
      concomitantly can simplify the process of obtaining pretravel prophylaxis and may
      help ensure that all needed vaccines are administered.

PMID- 12044275
TI  - Traveling with infants and children. Part 2: immunizations.

PMID- 12044274
TI  - Impact of the insect biting nuisance on a British youth expedition to Alaska.
AB  - BACKGROUND: The morbidity and nuisance factor associated with bites from
      mosquitoes and other insects are one of the many hazards faced by travelers,
      including those to the Arctic. A predeparture literature review suggested that
      insect bites were such a large problem in the area to be visited that they would
      probably have a significant impact on expedition activities. Therefore, we set
      out to assess the extent of the insect biting nuisance, focussing particularly on
      interference with expedition activities, in order to make recommendations for
      future expeditions to this area. The number of bites and their effects was
      examined on a 6-week British youth expedition to Alaska in July/August 1999.
      METHODS: A weekly "Insect Biting Nuisance Questionnaire" was distributed to each
      expedition member (total 72) to record the number of bites received over the
      previous week, a subjective grading of severity and itchiness, the extent of
      interference with expedition activities, any complications from the bites, and
      details about prevention and treatment. RESULTS: The questionnaire response rate
      was 64%, which was a representative sample. The median number of bites per person
      over the entire 6-week period was 33, with females and younger expeditioners
      tending to receive more bites. Multivariate analysis suggested that younger age
      was associated with more severe and itchier bites. Sleep was disturbed by itching
      on only 4% (68/1918) of nights. Generally, the bites were thought not to
      interfere with expedition activities (median score for interference 0; range 0
      10). CONCLUSION: The number of bites and their impact on expedition activities
      were both lower than expected. Thus, it is recommended that expeditions and
      independent travelers to this area do not need to increase time spent in the
      field to compensate for expedition man days lost due to problems associated with
      the insect biting nuisance.

PMID- 12044276
TI  - Malaria in elderly nonimmune travelers.

PMID- 12044277
TI  - Single grand mal seizures provoked by altitude?

PMID- 12044278
TI  - Dermatobia hominis myiasis: an emerging disease among travelers to the Amazon
      basin of Bolivia.

PMID- 12044279
TI  - Acute Schistosoma mansoni infection with progression to chronic lesion in Italian
      travelers returning from Cameroon, West Africa: a diagnostic and prevention
      problem.

PMID- 12044280
TI  - Murine typhus poorly responsive to ciprofloxacin: a case report.

PMID- 12044281
TI  - Neck irradiation or surgery may predispose to severe acute mountain sickness.

PMID- 12044282
TI  - Rat rabies in Phetchabun Province, Thailand.

PMID- 12044283
TI  - Clinical implications of antimicrobial resistance: how big is the problem?
AB  - This presentation addresses the question of the size of the antimicrobial
      resistance problem by examining the monitoring of antimicrobial use and
      resistance. It focuses on the main sources of information, possible pitfalls of
      the data and the susceptibility of the main pathogens responsible for
      bacteraemias in England and Wales. It addresses some of the difficulties in
      establishing the link between antimicrobial resistance and antimicrobial
      prescribing and concludes with some thoughts on necessary developments.

PMID- 12044284
TI  - Regulation of antimicrobial prescribing practices--a strategy for controlling
      nosocomial antimicrobial resistance.
AB  - Approximately 10% of hospital in-patients in the UK acquire nosocomial infection,
      with an increasing number of these infections caused by multiresistant organisms.
      It is essential to halt the development and spread of antibiotic resistance among
      hospital pathogens. The relationship between antibiotic use and the development
      of antibiotic resistance in microorganisms is a subject of ongoing controversy
      and research. However, there is a general acceptance that control of antibiotic
      prescribing within hospitals is fundamental to controlling the development of
      nosocomial antibiotic resistance. In order to achieve this, there is a need to
      design and successfully implement targeted antibiotic policies based on local
      patterns of resistance. Traditional educational methods used alone for executing
      such policies have not been shown to be effective. Computer-based technology
      shows great promise but will require considerable resource allocation for its
      installation. Of equal importance, the Infection Control Team must be given a
      high profile. Robust surveillance systems to gather epidemiological data on local
      prescribing practices, hospital infection control policy compliance, antibiotic
      resistance and hospital infection rates need to be set up within individual
      hospitals. The appointment of an anti-infective pharmacist should be considered.
      Delivery of an integrated antibiotic and infection control service requires a co
      ordinated, multidisciplinary team approach with clear leadership. Finally, in
      order for any strategy to be successful, the full support of hospital management
      is essential.

PMID- 12044285
TI  - Penicillin-resistant pneumococci-implications for management of community
      acquired pneumonia and meningitis.
AB  - Penicillin-nonsusceptible Streptococcus pneumoniae isolates have become
      increasingly prevalent worldwide. They are well-known agents of community
      acquired infections such as otitis media, pneumonia and bacterial meningitis.
      Therapy of pneumococcal infections is made difficult by the emergence and spread
      of bacterial resistance to penicillin and other beta-lactams, as well as other
      antimicrobials such as macrolides. This article reviews current concepts of
      epidemiology and the implications of penicillin-nonsusceptible pneumococci for
      management of community-acquired pneumonia and meningitis.

PMID- 12044286
TI  - The diagnosis and management of multiple-drug-resistant-tuberculosis at the
      beginning of the new millenium.
AB  - Multiple-drug-resistant tuberculosis (MDRTB) is more difficult to treat and the
      treatment is less likely to produce favourable results compared to treatment of
      drug-sensitive disease. Success requires close co-operation between the
      laboratory, which defines a case as MDRTB, and the clinical team, who will treat
      it as well as the public health staff who will address aspects of contact tracing
      and institutional cross-infection. National surveys have indicated that MDRTB
      occurs at a higher rate in some countries such as Estonia and Latvia (14.1% and
      9% respectively, in 1998) and Russia (although there are only limited validated
      data). In contrast, in Western Europe and in some countries of Eastern Europe,
      such as the Czech Republic, Slovenia, Slovakia and Poland with good tuberculosis
      (TB) prevention and treatment programmes, the combined MDRTB prevalence was 1% or
      less. The early diagnosis of MDRTB and case management by experienced teams from
      the outset remains the best hope clinically for these patients. Adequately
      supervised and prolonged combination chemotherapy is essential, with drug choice
      governed mainly by quality-controlled in vitro drug susceptibility data. There is
      a more limited role for surgery, and immunomodulating therapy, such as the use of
      gamma-interferon, may have a useful adjunct role. Clearly the most important
      therapeutic modality for MDRTB is to treat drug-sensitive TB correctly in the
      first instance and prevent the emergence of resistant TB.

PMID- 12044287
TI  - Resistance in viruses other than HIV.
AB  - The aim of this brief paper is to summarize the ways in which viruses develop
      resistance to currently licensed anti-viral drugs and to comment on their
      clinical relevance. Specific examples will be chosen to emphasize basic
      principles of the development of resistance and readers are referred elsewhere to
      a summary of resistance in HIV that follows the same principles.

PMID- 12044288
TI  - Novel agents for resistant Gram-positive infections--a review.
AB  - Gram-positive infections have increased in recent years, particularly those that
      are of nosocomial origin, leading to a broad use of agents with activity against
      these pathogens. Concomitantly, antimicrobial resistance of these pathogens also
      became widespread. Among the most common Gram-positive resistant pathogens are:
      Streptococcus pneumoniae, resistant to penicillin and macrolides, methicillin
      resistant Staphylococcus aureus (MRSA), glycopeptide-intermediately-resistant S.
      aureus (GISA), methicillin-resistant S. epidermidis, glycopeptide-resistant
      enterococci and vancomycin-resistant enterococci (VRE). The response of the
      pharmaceutical industry to this challenge was the development of new antibiotics
      active against these pathogens. Among these antibiotics, this review will focus
      on: linezolid, an oxazolidinone; GAR-936, a tetracycline derivative; daptomycin,
      a lipopeptide; and ortivancin (LY-333328), a glycopeptide related to vancomycin.
      Except for linezolid, which has been recently launched in many countries, all
      other agents referred to in this review are still at various developmental
      stages. It is hoped that in the near future most of these agents will be approved
      and thus the grim outlook of patients infected with resistant Gram-positive
      bacteria may improve.

PMID- 12044289
TI  - Antifungal drug resistance: does it matter?
AB  - The objectives of this review are: to review the modes of action of currently
      available antifungal drugs; to define drug resistance and discuss the mechanisms
      by which fungi can develop resistance to antifungal drugs; to consider the
      epidemiological and host factors that contribute to the outcome of antifungal
      therapy and whether the available in vitro susceptibility test methods can
      reliably predict clinical response; and to assess the overall relevance of drug
      resistance to the outcome of fungal infections. The incidence of antifungal drug
      resistance among pathogens causing invasive fungal infections appears to be
      increasing. In the case of Candida spp., this may in part be a consequence of
      selective pressure brought about by more intensive antifungal use leading to a
      'pathogen shift'. Non-albicans Candida spp. are more likely to demonstrate
      reduced susceptibility to fluconazole compared to C. albicans. Susceptibility
      breakpoints developed by the National Committee for Clinical Laboratory Standards
      to test azoles and flucytosine against Candida spp. are helpful in guiding
      therapy. Antifungal drug resistance in yeasts is of clinical importance.
      Increasingly reliable methods of in vitro susceptibility testing can help predict
      clinical response to therapy, but other considerations, including host- and drug
      related factors, can also have an important bearing on the ultimate outcome of
      treatment.

PMID- 12044291
TI  - Towards building truly global professional associations: the role of
      international congresses.

PMID- 12044294
TI  - Varicella pneumonia in patients with HIV/AIDS.
AB  - OBJECTIVE: To determine the potential role of steroid therapy combined with early
      antiviral and supportive care in patients infected with human immunodeficiency
      virus (HIV) with varicella pneumonia. MATERIALS AND METHODS: A retrospective
      review was conducted of the incidence, clinical course, and outcome of varicella
      pneumonia in patients with HIV or acquired immunodeficiency syndrome (AIDS).
      RESULTS: Seven of 12 patients (58%) who were hospitalized with chickenpox
      developed clinically severe varicella pneumonia. All patients had advanced
      immunosuppression and all developed diffuse reticulonodular radiographic
      abnormalities, although two patients had normal chest radiographs on admission.
      All patients received antiviral therapy within 12 hours of hospital admission.
      The overall mortality rate was 43%. Six patients were treated with systemic
      corticosteroids in addition to antiviral agents, including all four of the
      survivors. CONCLUSIONS: Hospitalized patients with HIV or AIDS with chickenpox
      are at high risk for developing varicella pneumonia. There is a potentially high
      rate of death despite prompt initiation of appropriate antiviral therapy.
      Intensive care management and adjunctive use of systemic corticosteroids may
      improve outcome.

PMID- 12044295
TI  - Clinical and epidemiologic aspects of human immunodeficiency virus-1-infected
      children in Buenos Aires, Argentina.
AB  - BACKGROUND: Argentina has the sixth largest number of cumulative pediatric cases
      of acquired immunodeficiency syndrome (AIDS) in the Americas; therefore, this
      study was designed to characterize human immunodeficiency virus-1 (HIV-1)
      infection in children in Buenos Aires, Argentina. MATERIALS AND METHODS: Medical
      records of 389 children at risk and infected with HIV-1, an urban population
      followed by the AIDS Reference Center at the Hospital de Ninos "Dr. Ricardo
      Gutierrez" of Buenos Aires, from February 1990 to June 1997, were retrospectively
      reviewed. Mother-infant pairs were analyzed according to clinical and
      epidemiologic patterns. RESULTS: Perinatal transmission occurred in 94.9% of the
      389 cases classified as seroreverter (n=104, 26.7%), exposed (n=64, 16.4%),
      asymptomatic (n=13, 3.4%), and symptomatic patients (n=208, 53.5%); 132 patients
      met the Centers for Disease Control and Prevention (CDC) criteria for AIDS. The
      main maternal risk factor was sexual transmission 58.9% (73.4% of their sexual
      partners were injection drug users [IDU]). Among the AIDS patients, the most
      common AIDS-defining condition and death-related disease were severe bacterial
      infection and Pneumocystis carinii pneumonia, respectively. Death occurred in 51
      of 221 HIV-infected children. Low CD4 was related to death (P < 0.001). Mortality
      was estimated for two periods: January 1990 to December 1995 (G1) and January
      1996 to May 1997 (G2). In G1, 37 of 127 (29.1%) died compared with 14 of 154
      (9.1%) in G2 (P=0.001). The median age of death was 10 months for G1 and 29
      months for G2 (P=0.01). The 3-year survival rate was 72% for G1 and 87% for G2
      (log rank P=0.06). CONCLUSIONS: Intravenous drug use is the leading risk factor
      among parents of children exposed to HIV. Infant mortality was related to age
      less than 12 months, low CD4 count, severe bacterial infection and P. carinii
      pneumonia. In this study, P. carinii pneumonia prophylaxis and combined
      antiretroviral therapy routinely implemented since 1996 has demonstrated a trend
      toward increased survival rates (P=0.06) and a lower mortality rate (P=0.001).

PMID- 12044296
TI  - Changes in bloodstream infections in HIV-positive patients in a university
      hospital in Spain (1995-1997).
AB  - OBJECTIVES: The Hospital Universitario Germans Trias i Pujol is a 600-bed center
      serving 700,000 inhabitants including 1800 patients with HIV infection in
      Catalonia (Spain). Highly active antiretroviral therapy (HAART) became available
      at the end of 1996. Thus, the period 1995 1997 was considered appropriate for
      evaluating possible epidemiological changes in bloodstream infections (BSI) in
      HIV-infected patients. METHODS: All significant bloodstream infections, including
      mycobacteremia and fungemia, observed in HIV-positive patients from January, 1995
      to December, 1997 have been included in the study. RESULTS: One hundred and
      eighty six cases were evaluated, in whom a decrease in BSI was observed (68 in
      1995, 86 in 1996, 32 in 1997). Over time, we observed an improvement in the
      immunologic situation of the patients (1995: CD4 <50/mm3 73.8% vs 1997: CD4
      <50/mm3 45.5% (P=0.05)). The source of BSI was known in 80.7% of the episodes.
      BSI secondary to catheter and respiratory infections prevailed in 1995, whereas
      an increase in bacteremias related to intravenous drug use, with or without
      endocarditis, was seen in 1997. The most frequent isolates were Mycobacterium
      avium intracellulare (23) (MAI), M. tuberculosis (20), Staphylococcus aureus
      (20), coagulase-negative staphylococci (16), Salmonella spp. (16) and
      Streptococcus pneumoniae (15). In 1997, a decrease was observed in the isolation
      of Gram-negatives and Mycobacterium spp. with S. aureus and enterococci
      prevailing. CONCLUSIONS: The prevalence of bloodstream infections in HIV-positive
      patients has decreased since the introduction of HAART and the immunologic state
      has improved. Furthermore there is a trend to a decrease or disappearance of
      microorganisms, such as Pseudomonas spp., Mycobacterium tuberculosis, MAI or
      fungi related to severe immunosuppression. Lastly, bacteremia caused by the
      active use of intravenous drugs remains stable with the highest percentage in
      Spain.

PMID- 12044297
TI  - The role of injection drug use in the emergence of Human Immunodeficiency Virus
      infection in Estonia.
AB  - OBJECTIVE: This article reviews the marked increase in human immunodeficiency
      virus (HIV) among injection drug users (IDU) in Estonia, a former Soviet Union
      republic bordering the Baltic Sea. HIV infection associated with injecting drug
      use has been reported worldwide. In Eastern Europe large-scale HIV epidemics have
      been observed from 1995 onward, after injection drug use (IDU) communities became
      infected. MATERIALS AND METHODS: In Estonia, surveillance of HIV infection is
      based on the mandatory universal notification of newly identified cases, with the
      same reporting principles in use throughout the last decades. By legal
      regulations every sample sent for HIV testing has to be coded (on the testing
      form) to identify the transmission category it belongs to. HIV testing was
      introduced in Estonia in 1987; by now over 2 million HIV tests have been
      performed. RESULTS: To date since 1987, 1305 cases of HIV have reported in
      Estonia. The incidence of HIV infections remained very low until recently, even
      when a considerable rise occurred in the incidence of sexually transmitted
      diseases, especially syphilis. Through 1999, only 96 cases of HIV had been
      reported nationally. Since then however, a dramatic increase has occurred. The
      cumulative data, including the information recorded on HIV testing forms and
      clinical records suggest that IDU was a factor in nearly 90% of the new HIV cases
      reported in year 2000. CONCLUSIONS: HIV infection appeared in Estonia much later
      than in many other parts of the world, so the experience from other countries
      that have confronted with the challenges of HIV could be of great help and
      importance for Estonia. The IDU related HIV infection epidemic in Estonia
      emphasizes an urgent need for preventive measures for IDUs as the target group.

PMID- 12044298
TI  - Treatment failure in intestinal strongyloidiasis: an indicator of HTLV-I
      infection.
AB  - BACKGROUND: The association of severe strongyloides with HTLV-I is well known;
      however, the seroprevalence of HTLV-I in other groups with strongyloidiasis is
      still unknown. We conducted a prospective study in patients with intestinal
      strongyloidiasis without known immunodepression who failed to respond to standard
      therapy with ivermectin or thiabendazole (failure was defined as one positive
      stool examination at the post-therapy follow up). All these patients were tested
      for HTLV-I by ELISA and Western Blot. RESULTS: Forty seven patients were
      evaluated: 74.5% (35 out of 47) were HTLV-I positive, without significant
      difference between males (76%) and females (72.7%). CONCLUSIONS: We recommend
      that all patients with uncomplicated intestinal strongyloidiasis, who fail
      standard therapy, be studied for HTLV-I infection.

PMID- 12044299
TI  - Identification of Tula hantavirus in Pitymys subterraneus captured in the Cacak
      region of Serbia-Yugoslavia.
AB  - BACKGROUND: Atypical serum neutralizing antibody responses to prototype strains
      of Puumala viruses in some patients with hemorrhagic fever with renal syndrome
      (HFRS) have long suggested the existence of other hantaviruses in the Balkans.
      OBJECTIVE: To determine the presence of arvicolid rodent-borne Puumala-like
      hantaviruses in Yugoslavia. MATERIALS AND METHODS: Using reverse transcript
      polymerase chain reaction, Tula virus RNA was amplified from lung tissues of a
      European pine vole (Pitymys subterraneus) captured in 1987, following an outbreak
      of HFRS in the Cacak region of Serbia-Yugoslavia. RESULTS: Sequence analysis of
      the entire coding region of the S segment and a 948-nucleotide region of the G2
      glycoprotein-encoding M segment revealed divergence of approximately 14% from
      Tula virus strains harbored by European common voles (Microtus arvalis) captured
      in Central Russia and the Czech Republic. However, nearly complete identity was
      found in the corresponding deduced amino acid sequences. Moreover, phylogenetic
      trees constructed by the maximum parsimony and neighbor-joining methods indicated
      that this Pitymys-borne hantavirus shared a common ancestry with other Tula virus
      strains. CONCLUSIONS: The data demonstrate that Pitymys subterraneus also serves
      as a rodent reservoir of Tula virus in Serbia-Yugoslavia. To what extent this
      represents virus spillover from Microtus arvalis warrants further investigation.

PMID- 12044300
TI  - Randomized, double-blind, placebo-controlled trial of oromucosal low-dose
      interferon following prednisone withdrawal for chronic hepatitis B infection in
      Filipino patients.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oromucosal low-dose human
      lymphoblastoid interferon alpha (IFN-alpha-n1 [INS]) following steroid withdrawal
      in Filipino patients with chronic replicative hepatitis B virus (HBV) infection.
      STUDY DESIGN: Randomized, double blind, placebo-controlled trial on IFN-alpha-n1
      [INS], two tablets of 200 IU each or placebo, given sublingually once daily for
      eight months following steroid or placebo priming and withdrawal. RESULTS: A
      statistically significant clearance of hepatitis B e antigen (HBeAg) (50%) and
      seroconversion to positive antibody to HBeAg (anti-HBe) (42.9%) was noted in
      those given IFN-alpha-n1 [INS] compared with the placebo group. Clearance of
      serum HBV-DNA was not significantly different and none cleared HBsAg in both
      groups. More patients (57%) had normalization of ALT on IFN-alpha-n1 [INS]
      compared with controls (31.3%). Oromucosal IFN-alpha-n1 [INS] was devoid of any
      evidence of toxicity. CONCLUSION: This study conducted on a limited number of
      patients demonstrates the potential efficacy of oromucosal IFN-alpha-n1 [INS] in
      chronic HBV infection with therapeutic benefit equal to parenterally administered
      interferon alpha (IFNalpha) but without the side effects of myelosuppresion.
      Owing to the small population studied, we are unable to extrapolate these
      findings to the general population of patients with chronic HBV infection. A
      large-scale study is needed to confirm these findings.

PMID- 12044301
TI  - Measles IgG seroprevalence prior to mass vaccination in Taiwan.
AB  - OBJECTIVES: Measles vaccine was licensed for use in Taiwan in 1968 and mass
      vaccination has been implemented since 1978. Serological surveys were conducted
      to characterize measles seroepidemiology prior to mass vaccination. METHODS:
      Measles IgG was quantitatively measured in 1564 serum samples collected from four
      populations (nationwide, urban, rural, and mountain areas) during 1974-80 with a
      commercial EIA kit. The nationwide samples covered age groups from 3 months to 19
      years, but the other three samples only covered school-aged children. The cut-off
      value of seropositivity was set at 100 mIU/ml. RESULTS: In the nationwide
      samples, measles IgG seroprevalence decreased from 50% at 3-5 months to 13% at 6
      11 months, then increased rapidly to 55% at 1-1.9 years and reached 98% at 7-7.9
      years of age; this was maintained to young adulthood. In all four samples,
      seroprevalence also reached >97% in individuals >10 years of age.
      Semiquantitative analysis found that 24%(10/42) of 1-1.9-year-old children but
      only 4%(1/24) of 15-19-year-old adolescents had low level measles IgG (100-399
      mIU/ml). In addition, the distribution of measles IgG level in 1-1.9-year-old
      children had two peaks at 200-399 and 1600-3199 mIU/ml, whereas only one peak at
      1600-3199 mIU/ml had been found in 15-19-year-old adolescents. The median age of
      measles infection (i.e. 50% seroprevalence) in Taiwan was 1.4 and 2.1 years,
      respectively, before and after excluding individuals with measles IgG 100-399
      mIU/ml that may have resulted from vaccination. CONCLUSIONS: Measles
      seroepidemiology in Taiwan in the 1970s seemed to be more similar to that in a
      developing country rather than in an industrialized country, and there was a low
      median age of infection.

PMID- 12044302
TI  - Characterization of pyrazinamide and ofloxacin resistance among drug resistant
      Mycobacterium tuberculosis isolates from Singapore.
AB  - OBJECTIVES: To evaluate rapid molecular approaches for the detection of
      pyrazinamide (PZA) and ofloxacin resistance, by screening 100 known drug
      resistant Mycobacterium tuberculosis isolates. METHODS: Mycobacterium
      tuberculosis isolates were tested for phenotypic resistance to pyrazinamide and
      ofloxacin using the BACTEC 460 radiometric method and the E-test, respectively.
      Mutation screening was done by amplifying the pncA, gyrA, and gyrB genes by the
      polymerase chain reaction (PCR) and direct automated sequencing. RESULTS: Twelve
      isolates were PZA-resistant and 8 of 12 (66.7%) isolates had missense mutations
      or deletions at the pncA gene, suggesting that mutation or deletion at the pncA
      gene is the major molecular mechanism of PZA resistance among the Singaporean
      isolates. Using the E-test, 48 isolates were resistant to ofloxacin, with minimum
      inhibitory concentrations of 4 microg/mL or higher. No mutations were observed at
      the quinolone resistance-determining region (QRDR) of gyrA in all isolates. At
      the QRDR of gyrB, mutations were present in 1 of 48 ofloxacin-resistant isolates
      and 0 of 19 ofloxacin-susceptible isolates. CONCLUSIONS: In Singapore, genotypic
      analysis of resistance to PZA and ofloxacin is inadequate and should be
      complemented by conventional methods.

PMID- 12044303
TI  - Prognostic factors of death in leptospirosis: a prospective cohort study in Khon
      Kaen, Thailand.
AB  - OBJECTIVES: To determine the prognostic factors of death in leptospirosis.
      METHODS: A prospective cohort study was conducted. One hundred and twenty one
      patients with clinically compatible leptospirosis, serologically confirmed, were
      recruited in this study. Clinical presentations and biochemical parameters on
      admission were selected as input variables for survival analysis. Multivariable
      Cox regression model was used to identify the prognostic factors of death.
      RESULTS: Most patients were male (94.2%), with the mean +/-SD age of 38+/-13.4
      years; 77.4% of them were farmers. Among the 121 patients, 1206 patient-days were
      observed. Seventeen patients died. Overall mortality rate was 1.4 per 100 patient
      days (95% confidence interval [CI]: 0.9-2.3). The causes of death included: a)
      pulmonary hemorrhage in eight (47.1%) patients; b) complicated acute renal
      failure in three (17.6%) patients; c) multiple organ failure in three (17.6%)
      patients; d) acute respiratory distress syndrome in two (11.8%) patients, and e)
      irreversible shock in one (5.9%) patient. Four independent risk factors
      associated with the mortality were identified, including hypotension (relative
      risk [RR], 10.3; 95% CI, 1.3-83.2; P<0.05); oliguria (RR, 8.8; 95% CI, 2.4-31.8;
      P<0.01); hyperkalemia (RR, 5.9; 95% CI, 1.7-21; P<0.01), and presence of
      pulmonary rales (RR, 5.2; 95% CI, 1.4-19.9; P<0.05). CONCLUSION: The presence of
      oliguria, hyperkalemia, pulmonary rales, or hypotension on admission in patients
      with leptospirosis indicated high risk of death. Intensive care and early
      intervention should be provided for patients who present with these risk factors.

PMID- 12044304
TI  - A pilot study of treatment of Buruli ulcer with rifampin and dapsone.
AB  - OBJECTIVE: Buruli ulcer disease (BU), caused by Mycobacterium ulcerans, is
      endemic in many regions of Africa and causes substantial physical disability.
      Surgical resection, currently the mainstay of clinical management of BU, is
      impractical in many endemic areas. Therefore, the study was undertaken to
      evaluate an antibiotic regimen for medical management of BU. METHODS: A
      randomized, placebo-controlled pilot study of dapsone plus rifampin versus
      placebo was conducted. RESULTS: Forty-one participants were recruited in a BU
      endemic zone of Cote d'Ivoire. Thirty persons completed the 2-month trial: 15
      were treated with placebo and 15 with dapsone and rifampin. On blinded evaluation
      of photographs of the ulcers, clinicians with experience examining BU judged that
      82% of ulcers in the treatment group improved compared with 75% in the placebo
      group (P=0.51). The median change in ulcer size was a decrease of 14.0 cm2 in the
      treatment group and a decrease of 2.5 cm2 in the placebo group (P=0.02), but
      initial ulcer sizes were larger in the treatment group (median 26.2 cm2) compared
      with the placebo group (median 4.8 cm2) (P=0.04). CONCLUSIONS: Results of this
      study indicate that larger studies of antimycobacterial therapy of BU are
      warranted and can be successfully undertaken.

PMID- 12044305
TI  - Pediatric visceral leishmaniasis in Albania.
AB  - OBJECTIVE: Visceral leishmaniasis (VL) in children is endemic in southern Europe
      but has not been previously reported from Albania. This prospective study reports
      the clinical and laboratory findings in 50 children with visceral leishmaniasis,
      the value of a direct agglutination test (DAT), and the result of treatment with
      meglumine antimonate. MATERIALS AND METHODS: Sera obtained from 50 children with
      VL confirmed by bone marrow examination, 40 household contacts, and 30
      hospitalized children with other infections were examined using DAT. RESULTS:
      Clinical features included fever (100%), hepatosplenomegaly (100%), pallor
      (100%), weight loss (98%), vomiting (68%), diarrhea (32%), and bleeding disorders
      (8%). Laboratory findings were anemia (94%), neutropenia (85%),
      hypergammaglobulinemia (70%), and thrombocytopenia (22%). Thirty children who
      developed secondary bacterial infections had significantly lower hemoglobin and
      neutrophil counts (P<0.0001). Direct agglutination test had a sensitivity of 98%,
      a specificity of 100%, and a positive predictive value of 100%. One child with
      severe generalized bleeding died within 48 hours of admission before receiving
      treatment. CONCLUSION: The direct agglutination test was highly valuable in
      diagnosis of VL in this series. Meglumine antimonate was an effective therapeutic
      agent. Post-treatment bone marrow examination confirmed recovery in all patients.
      There were no relapses of VL during one-year follow up.

PMID- 12044307
TI  - Epidemiological observations of the judicious use of antibiotics in a pediatric
      teaching hospital.
AB  - OBJECTIVE: This study in a tertiary care teaching center with 361 beds was
      conducted to assess use, misuse, and abuse of antibiotics. MATERIALS AND METHODS:
      Every day of the study, a computer program was used to compile a list of
      patients' bedside records. On a specific day, the bedside charts of selected
      patients were reviewed to determine whether: (1) a justification for antibiotic
      prescription was recorded; (2) duration of antibiotic therapy had been defined;
      (3) suitable cultures had been obtained; and (4) treatment was appropriate for
      the infection to be treated. For 6 months, charts were evaluated 3 days per week.
      RESULTS: Of 750 bedside charts 500 (67%) were selected for review. Of the 500
      patients, 175 (35%) did not receive antibiotics. The abuses or misuses of
      antibiotics most frequently observed among the 325 treated patients were no
      record of justification for the antibiotic prescribed (130/325, 40%); no
      appropriate blood or fluid samples obtained for culture (45/325, 14%); no
      subsequent control cultures or cultures obtained before modifying therapy
      (80/175, 46%); no indication of a planned duration of therapy (180/325, 55%); and
      improper dosage prescribed in relation to weight (25/325, 8%). Abuse or misuse of
      antibiotics was more frequently observed among surgical patients than among
      nonsurgical patients (P<0.05). CONCLUSION: Rational use of antibiotics should be
      emphasized in every training program as a main strategy to control the increase
      in drug resistance and to prolong the usefulness of antibiotics.

PMID- 12044306
TI  - Bacteremias caused by Escherichia coli in cancer patients - analysis of 65
      episodes.
AB  - OBJECTIVES: The aims of this study were to evaluate risk factors, clinical
      presentation, outcome and antimicrobial susceptibility in patients with
      Escherichia coli bacteremia occurring over seven years in a single cancer
      hospital. METHODS: Sixty five episodes of bacteremia from E. coli appearing over
      seven years from 12,301 admissions in a single cancer institution were
      retrospectively analyzed. RESULTS: The proportion of bacteremia caused by E. coli
      among Gram-negative bacteremia was 20.8% (the second most common organism after
      Pseudomonas aeruginosa), and infection-associated mortality was 17%. The
      incidence in 1989-1995 varied from 14.3 to 24.7%. The most common risk factors
      were: solid tumors as the underlying disease (70.7%); central venous catheter
      insertion (32.3%); prior surgery (46.2%), and prior chemotherapy within 48 h
      (44.4%). Neutropenia and urinary catheters did not place patients at high risk in
      any of the subgroups. When we compared the two subgroups of 61 cases of
      bacteremia - monomicrobial and polymicrobial (when E. coli was isolated from
      blood culture with another microorganism) - we found that acute leukemia and
      breakthrough (recurrence while receiving antibiotics) bacteremia were more
      frequently associated with polymicrobial E. coli bacteremia. There was also a
      difference in infection-associated mortality: monomicrobial bacteremia due to E.
      coli only had a significantly lower mortality in comparison with polymicrobial E.
      coli bacteremia (8.9 vs 35.0%, respectively; P<0.03). CONCLUSION: The
      susceptibility of 115 E. coli strains isolated from 65 episodes of bacteremia was
      stable. Only two episodes caused by quinolone-resistant strains occurred, both in
      1995, after six years of using ofloxacin for prophylaxis in neutropenic patients
      in our hospital. We found that 85.2-91.3% of all strains were susceptible to
      aminoglycosides, 97.8% to quinolones, and 90-100% to third generation
      cephalosporins and imipenems. The patients most commonly infected had solid
      tumors and the mortality was only 17%.

PMID- 12044308
TI  - Extra-abdominal infections due to Gemella species.
AB  - OBJECTIVES: To understand the role of Gemella species as a pathogen causing extra
      abdominal infections in the Hospital General Universitario Gregorio Maranon.
      MATERIALS AND METHODS: Between 1994 and 1998, one or more isolates of Gemella sp.
      were found in 128 patients. The 113 patients with isolates from nonsignificant
      specimens or representing intra-abdominal infections were excluded. The clinical
      records of the remaining 15 patients were reviewed as well as the more recent
      literature. RESULTS: Mean age of patients was 41 years. The underlying conditions
      most frequently noted were intravenous drug users (n=6; 3 positive for human
      immunodeficiency virus), alcoholism (n=2), cardiovascular disease (n=2), chronic
      lung disease (n=2), diabetes (n=1), kidney transplant (n=1). The extra-abdominal
      infections were skin and soft tissue abscess (n=5), empyema (n=4), brain abscess
      (n=2), primary bacteremia (n=1), lung abscess (n=1), septic thrombophlebitis
      (n=1), complicated urinary tract infection (n=1). The infection was monomicrobial
      in six and polymicrobial in nine cases. Surgical drainage and betalactam
      antibiotics were used. The outcome was favorable in almost all cases.
      CONCLUSIONS: Gemella sp. should be included as a cause of localized soft-tissue
      abscesses, empyema, and bloodstream infection. No case of infective endocarditis
      was found. Although it is susceptible to several antibiotics, Gemella sp.
      requires a careful microbiologic diagnosis and a subtle clinical interpretation.

PMID- 12044309
TI  - Preeclampsia and cerebral palsy in low-birth-weight and preterm infants:
      implications for the current "ischemic model" of preeclampsia.
AB  - OBJECTIVE: One of the prevailing hypotheses for the pathogenesis of preeclampsia
      is the "ischemic model." It assumes that reduced uteroplacental perfusion is the
      primary step and the point of convergence of diverse pathogenic processes in the
      development of preeclampsia. One might expect a fetus under such "ischemic
      conditions" to be at an increased risk of later development of cerebral palsy
      (CP). The objective of this study was to test the hypothesis that maternal
      preeclampsia increases the risk of CP in preterm and low-birth-weight infants.
      METHODS: A meta-analysis was performed based on published articles identified by
      searching computerized databases (MEDLINE, EMBASE, CINAHL, Current Contents,
      Biological Abstracts, and Dissertation Abstracts) from 1966 through 1999. Ten
      observational studies on the association between preeclampsia and CP were
      identified based on prespecified inclusion criteria. Two independent reviewers
      extracted data and assessed the methodological quality of eligible articles. Odds
      ratios (OR) of CP for preeclampsia from individual studies were pooled. MAIN
      OUTCOME MEASURE: Cerebral palsy. RESULTS: In case-control studies, preeclampsia
      was associated with a statistically significant decreased risk of CP [pooled
      adjusted OR, 0.50; 95% confidence interval (CI), 0.33-0.81; p < 0.01). In cohort
      studies, preeclampsia was associated with a nonstatistically significant reduced
      risk of CP (pooled OR, 0.91; 95% CI, 0.35-2.41; p > 0.05). CONCLUSIONS:
      Preeclampsia may be associated with a decreased risk of CP in preterm and low
      birth-weight infants. This challenges the currently held belief that reduced
      uteroplacental perfusion is the unique pathophysiological process in
      preeclampsia.

PMID- 12044310
TI  - Long-term follow-up in patients with a history of (H)ELLP syndrome.
AB  - OBJECTIVE: To provide long-term follow-up data on women with a history of
      hemolysis, elevated liver enzymes, and low platelets [(H)ELLP] syndrome regarding
      the risk of recurrence in subsequent pregnancies and disease in later life.
      METHODS: All women admitted to the Academic Medical Centre between January 1984
      and January 1996 with (H)ELLP syndrome and a living singleton fetus in utero were
      included. Women with known preexisting diseases were excluded. The (H)ELLP
      syndrome was defined as elevated liver enzymes (serum aspartate aminotransferase
      or serum alanine aminotransferase >or= 50 U/L) and low platelet count (< 100 x
      10(9)/L). Those patients with hemolysis (LDH >or= 600 U/L) were classified as
      HELLP, the remaining ones were classified as ELLP. The participants were asked to
      fill out a questionnaire regarding their general health and their own obstetric
      and medical history and that of their first-and second-degree relatives. RESULTS:
      One hundred sixteen (94%) of 123 women responded; 4 women had died. The median
      age of the group was 36.0 years at completion of the questionnaire; the median
      interval after the index pregnancy was 5.7 years (3-12.9). The incidence of
      hypertension requiring medical treatment was three times higher than in a
      reference population of Dutch women between 20 and 40 years old. The need for
      psychological support was frequent. Thirty-nine patients (34%) refrained from
      further pregnancies. Twenty-nine percent of the first subsequent pregnancies were
      complicated by gestational hypertension (GH), but only 2% had (H)ELLP syndrome.
      Birth weight was, on average, 1385 g higher and gestational age at delivery 5
      weeks later in the first subsequent pregnancy irrespective of a recurrence of GH.
      A family history of cardiovascular disease or preeclampsia was common in the
      total group; however, this did not influence the recurrence rate. Multiparity,
      gestational age at delivery <30 weeks, and birth weight <1000 g in the index
      pregnancy increased the risk of recurrence of GH in the first subsequent
      pregnancy significantly. CONCLUSIONS: (H)ELLP syndrome is a severe complication
      of pregnancy that has not only short-term but also long-term sequelae.

PMID- 12044311
TI  - Evaluation of ambulatory and self-initiated blood pressure monitors by pregnant
      and postpartum women.
AB  - OBJECTIVE: To investigate the acceptability of an ambulatory blood pressure (ABP)
      monitor (SpaceLabs 90207) and a self-initiated blood pressure monitor (Omron HEM
      705CP) to pregnant women. METHODS: Acceptability of the SpaceLabs 90207 and Omron
      HEM- 705CP monitors was evaluated, using a modified British Hypertension Device
      assessment form, by () healthy, pregnant women at <15 weeks (n = 120), 35-37
      weeks (n = 81), and 5-9 weeks postpartum (n = 86); and () women with preeclampsia
      (n = 52). MAIN OUTCOME MEASURES: A monitor was acceptable if a woman graded the
      overall impression as "good" or "very good." RESULTS: Healthy women at <15 and 35
      37 weeks' gestation and preeclamptic women reported the SpaceLabs 90207 monitor
      caused discomfort in 54%, 52%, and 60%, interfered with activities in 38%, 40%,
      and 23%, and disturbed sleep in 62%, 52% and 31%, respectively. Fewer than 12% in
      any group reported these problems with the Omron HEM-705CP monitor. In the 78
      women who evaluated both monitors at 35-37 weeks, the SpaceLabs 90207 and Omron
      HEM-705CP were acceptable to 78% and 95% of healthy women, respectively (p =
      0.005). Women with preeclampsia rated the Space-Labs 90207 as "bad" or "fair"
      (14%), "good" (58%), and "very good" (28%) compared with "bad" or "fair" (8%),
      "good" (28%), and "very good" (64%) for the Omron HEM-705CP monitor (p = 0.009).
      CONCLUSIONS: Pregnant women found the less intensive blood pressure monitoring
      with the Omron HEM-705CP more acceptable than the 24-h ABP monitoring with the
      SpaceLabs 90207. If accurate self-initiated blood pressure devices become
      available, pregnant women would prefer this method of home blood pressure
      monitoring.

PMID- 12044312
TI  - Low-molecular-weight heparin for the prevention of obstetric complications in
      women with thrombophilias.
AB  - OBJECTIVE: To evaluate the benefit of combined low-molecular-weight (LMW) heparin
      and aspirin for prophylaxis in women carriers of thrombophilia who had previously
      suffered from severe obstetric complications. METHODS: The 33 studied women had
      an earlier pregnancy complicated by severe preeclampsia, abruptio placentae,
      intrauterine growth retardation, or intrauterine fetal death. All were
      subsequently diagnosed as carrying inherited thrombophilias. In their subsequent
      pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin,
      Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were
      found to be homozygotes for the methylenetetrahydrofolate reductase mutation also
      received folic acid supplementation throughout their pregnancy. RESULTS: Low
      molecular-weight heparin was well tolerated and none of the women or the newborns
      developed any hemorrhagic complications. Only three (9.1%) of the women developed
      pregnancy complications. The mean gestational age and the mean birth weight at
      delivery in the previously complicated pregnancies were 32.1 +/- 5.0 weeks and
      1175 +/- 590 g, respectively, compared to 37.6 +/- 2.3 weeks and 2719 +/- 526 g,
      respectively, in the treated pregnancies (p < 0.001). CONCLUSIONS: This
      uncontrolled trial suggests that patients with obstetric complications and an
      inherited thrombophilia may benefit from treatment with combined LMW heparin and
      aspirin in subsequent pregnancies. However, this needs to be verified by
      controlled trials before considering clinical application.

PMID- 12044313
TI  - Influence of reduced intracellular glutathione availability on the secretion of
      vasoactive substances by human umbilical vein endothelial cells.
AB  - OBJECTIVE: Oxidative stress might be the reason for endothelial dysfunction in
      preeclampsia. The glutathione-peroxidase system is one of the primary
      antioxidants in the endothelium. We tested the effect of oxidative stress by
      reduction of glutathione availability on the secretion of vasoactive substances
      in endothelial cells. METHODS: Endothelial cells in culture were incubated with
      different concentrations of buthionine-[S,R]-sulfoximine (BSO) or 1-chloro-2,4
      dinitrobenzene (CDNB), both leading to a reduced intracellular availability of
      glutathione. The secretion of the vasoactive substances nitric oxide (NO),
      endothelin-I (ET-1), and prostacyclin (PGI2) was measured with respect to
      vitality and proliferation rate of the endothelial cells in culture. MAIN OUTCOME
      MEASURE: Effect of oxidative stress on the secretion of vasoactive substances
      from endothelial cells. RESULTS: The oxidants CDNB and BSO have (in
      concentrations before evidence of cytotoxicity) a stimulating effect on the
      production of PGI2, they inhibit NO availability, and they do not significantly
      interfere with ET-1 production. Conclusion Oxidative stress in vitro induces an
      imbalance in the secretion of NO, ET-1, and PGI2 in endothelial cells.

PMID- 12044314
TI  - The diversity of diagnoses of preeclampsia.
AB  - OBJECTIVE: To document the diversity of definitions and diagnoses of the
      hypertensive disorders of pregnancy reported in major medical journals as a
      preliminary step from which future documents may be developed concerning the
      classification and diagnosis of the hypertensive disorders of pregnancy. METHODS:
      A systematic review was undertaken of articles published between 1997 and 1998
      researching "preeclampsia" in nine internationally recognized journals. Each
      article was assessed to establish the features used by the authors to define
      preeclampsia and its major defining variables (i.e., proteinuria and
      hypertension). Documentation of aspects of the blood pressure measurement
      technique was also noted. RESULTS: One hundred thirty-five articles were studied,
      demonstrating a wide variety in the authors' definitions of preeclampsia,
      "significant" proteinuria, and hypertension. In up to 13% of articles, one or
      more of these terms was not defined and documentation of the blood pressure
      measurement technique was generally poor. The diversity of reporting was of such
      magnitude that the groups of women in these studies could rarely be considered
      truly comparable. CONCLUSION: Scientific and clinical research groups are
      studying different preeclamptic groups as a result of using different definitions
      of this condition. As comparison of results among studies is fundamental to the
      correct elucidation of knowledge about preeclampsia, standardization of the
      classification and diagnostic criteria of the hypertensive disorders of pregnancy
      should be a major priority of societies devoted to the study of these disorders.

PMID- 12044316
TI  - Fibronectin is a marker for organ involvement and may reflect the severity of
      preeclampsia.
AB  - OBJECTIVE: We have studied whether plasma fibronectin is related to a rise in
      blood pressure during normal pregnancy, whether it can be used for the early
      prediction of preeclampsia, and whether plasma fibronectin is a marker for organ
      involvement in preeclampsia. STUDY DESIGN: Two hundred twenty-eight healthy
      pregnant nullipara women were examined prospectively during pregnancy. Analyses
      of fibronectin in plasma were performed in pregnancy weeks 16, 24, 28, 32, and
      36. During the same period, 177 patients with suspected preeclampsia and/or
      intrauterine growth retardation (IUGR) were tested for plasma fibronectin, mainly
      in the third trimester. RESULTS: In the normal population of pregnant women
      (n=222/228), fibronectin levels were 0.35 +/- 0.06 g/L in pregnancy week 16 and
      0.43 +/- 0.12 g/L in week 36. These levels showed a positive correlation to blood
      pressure elevation during pregnancy (r=0.21, p=0.006). The six patients in this
      group (n=6/228) who later developed preeclampsia had higher fibronectin values
      0.42 +/- 0.07 g/L already in week 16 (p=0.023). In the population of women with
      suspected preeclampsia (preeclampsia, n=129; IUGR alone, n=17; hypertension or
      proteinuria during pregnancy, n=31), fibronectin values were significantly
      higher, 0.75 +/- 0.27 g/L than in the normal population. Patients with
      preeclampsia and laboratory signs of organ involvement (n=56) showed
      significantly higher fibronectin values (0.85 +/- 0.27 g/L) compared to
      preeclampsia without organ involvement (n=73) [0.76 +/- 0.22 g/L (p=0.03)].
      CONCLUSION: Our data show that fibronectin is related to blood pressure in
      pregnancy. Fibronectin values in women who develop preeclampsia are elevated
      already in pregnancy week 16 and were higher in those with laboratory signs of
      organ involvement.

PMID- 12044315
TI  - Homocysteine and cellular fibronectin are increased in preeclampsia, not
      transient hypertension of pregnancy.
AB  - OBJECTIVE: The objective of this study was to confirm that endothelial
      dysfunction is present in preeclampsia and absent in transient hypertension of
      pregnancy, and to determine whether the cardiovascular risk factor homocysteine
      is associated with the degree of endothelial dysfunction. METHODS: We measured
      cellular fibronectin (as a marker of endothelial injury) and total plasma
      homocysteine in samples collected at the time of admittance to labor and delivery
      in 17 women with preeclampsia (increased blood pressure, proteinuria, and
      hyperuricemia), 16 women with transient hypertension of pregnancy (only increased
      blood pressure), and 34 normal pregnant women. Each subject with preeclampsia was
      matched by prepregnancy body mass index, race, and gestational age at delivery to
      one subject with transient hypertension of pregnancy and two controls. RESULTS:
      Cellular fibronectin was found to be significantly increased in women with
      preeclampsia compared to subjects with transient hypertension of pregnancy or
      normal pregnant women (22.9 +/- 14.1 microg/mL versus 10.9 +/- 5.4 and 10.1 +/-
      6.2 microg/mL, respectively, p<0.0001). Similarly, total plasma homocysteine was
      also significantly increased in the women with preeclampsia compared to subjects
      with transient hypertension of pregnancy or normal pregnant women (8.3 +/- 2.5
      microM versus <5.5 +/- 2.2 and 5.4 +/- 3.4 microM respectively, p<0.01). However,
      contrary to our hypothesis, there was no apparent association between cellular
      fibronectin and homocysteine. CONCLUSIONS: The increased concentrations of
      homocysteine observed in preeclampsia are not a general feature of all
      hypertensive complications of pregnancy. Furthermore, endothelial dysfunction is
      present in preeclampsia and is not evident in transient hypertension of
      pregnancy. However, the apparent endothelial dysfunction in preeclampsia is not
      explained by the increase in homocysteine concentrations observed.

PMID- 12044317
TI  - Placental expression of cytokeratin 18 and serum levels of tissue polypeptide
      antigen in women with pregnancy-induced hypertension.
AB  - OBJECTIVE: We hypothesized that placental cytokeratin (CK) 18 expression and
      serum levels of tissue polypeptide antigen (TPA), a surrogate marker for CK 18,
      are increased among women with pregnancy-induced hypertension (PIH). METHODS:
      Serum levels of TPA were measured in 46 women with PIH and 46 controls, matched
      for gestational age and parity, using an immunoradiometric assay.
      Immunohistochemical detection of CK 18 was assessed in placental specimens of 24
      women with PIH and 20 controls. Results were correlated to clinical data.
      RESULTS: Cytokeratin 18 expression was found in the syncytiotrophoblast of 7 of
      20 (35%) and 18 of 24 (75%) placental specimens of controls and women with PIH,
      respectively (p = 0.008). Median serum levels of TPA in controls and women with
      PIH were 93.0 U/L (range: 12.5-281.6) and 154.2 U/L (range: 37.3-496.6),
      respectively (p = 0.001). Serum levels of TPA significantly influenced the odds
      of presenting with PIH, as well as the odds of developing severe disease (p =
      0.003, and p = 0.001, respectively). TPA values were significantly higher among
      women with severe PIH compared with women with mild PIH and controls, independent
      of gestational age (p = 0.004). Among women with severe PIH, serum TPA was
      inversely correlated with fetal birth weight (r = -0.3; p = 0.001) CONCLUSION:
      Cytokeratin 18 is overexpressed in the syncytiotrophoblast of women with PIH.
      Serum levels of TPA are elevated among women with PIH and correlate with disease
      severity and low fetal birth weight.

PMID- 12044318
TI  - Elevated maternal serum hCG in the second trimester increases prematurity rate
      and need for neonatal intensive care in primiparous preeclamptic pregnancies.
AB  - OBJECTIVE: This study was designed to investigate the association between the
      serum concentrations of maternal second trimester human chorionic gonadotropin
      (hCG) and the severity of preeclampsia. METHODS: At Kuopio University Hospital, a
      total of 487 preeclamptic primiparas had undergone maternal serum screening for
      Down's syndrome between January 1993 and December 1998. Of these, 37 women had
      unexplained elevated serum hCG concentrations [> 2.5 multiples of the median
      (MoM)], whereas the remaining 450 preeclamptic women had normal hCG results.
      Pregnancy characteristics and outcome measures in these groups were evaluated
      using logistic regression. RESULTS: Elevated midtrimester hCG concentrations were
      associated with higher rates of low-birth-weight infants, preterm delivery, and
      need for neonatal intensive care. The adjusted odds ratios was 2.11 [95%
      confidence interval (CI): 1.03-4.32], 2.08 (95% CI: 1.10-4.30), and 2.27 (95% CI:
      1.14-4.51), respectively. CONCLUSIONS: In primiparous preeclamptic pregnancies,
      an elevated maternal serum hCG concentration is a marker of early-onset and
      severe disease with significant maternal and perinatal morbidity. This finding,
      in turn, reinforces the association between elevated hCG concentrations and
      placental damage in early pregnancy. Elevated maternal serum hCG levels identify
      a subgroup of preeclamptic patients who deserve more intensive observation.

PMID- 12044320
TI  - Connexin expression is not altered in omental resistance vessels from women with
      preeclampsia.
AB  - OBJECTIVE: To compare connexin expression in omental resistance arteries from
      preeclamptic women and normal gravidas. METHODS: Small arteries (approximately
      200-400 microm i.d.) were dissected from omental fat biopsies, taken at cesarean
      delivery from normotensive and preeclamptic women. Vessels were frozen and
      homogenized, then connexin-43 protein was detected by Western blot and
      quantitated by comparison with alpha-actin. RESULTS: Connexin-43 was detected in
      all specimens, primarily in its phosphorylated form. Abundance did not differ
      between vessels from preeclamptic and normotensive gravidas. CONCLUSIONS: Phasic
      activity in omental resistance vessels from preeclamptic women likely depends on
      abnormal genesis of an oscillatory signal rather than on more extensive gap
      junctional communication between vascular cells.

PMID- 12044319
TI  - An endothelial nitric oxide synthase gene polymorphism is associated with
      preeclampsia.
AB  - OBJECTIVE: We sought to test the hypothesis that a polymorphism of the
      endothelial nitric oxide synthase gene (NOS3) is associated with preeclampsia.
      METHODS: We collected and performed polymerase chain reaction (PCR) on genomic
      DNA from pregnant patients with and without preeclampsia. Patient history and
      clinical course were evaluated. MAIN OUTCOME MEASURE(S): Frequency of the intron
      4 polymorphism of NOS3 (designated allele A) among patients with preeclampsia
      compared with controls. Clinical features of patients with preeclampsia and the A
      allele compared with those patients with preeclampsia who did not have the A
      allele. RESULTS: The frequency of the A allele was 0.10 among controls versus
      0.39 among patients with preeclampsia (p < 0.01). The odds ratio of developing
      preeclampsia when at least one A allele was present was 6.5 [95% confidence
      interval (CI): 2.1-19.7]. After adjusting for ethnic variation, the odds ratio
      increased to 7.2 (95% CI: 2.0-25.5). Among patients with preeclampsia, systolic
      blood pressure at the time of admission was higher for patients with at least one
      A allele compared with patients homozygous for the B allele (168 versus 156 mm
      Hg; p = 0.03), independent of gestational age (p = 0.01). CONCLUSION: These data
      provide evidence for an association between NOS3 and preeclampsia. In defined
      ethnic groups, this NOS3 may offer predictive information regarding the
      subsequent development of preeclampsia and its clinical course.

PMID- 12044321
TI  - Immunocytochemical localization of endothelin-1 in human placenta from normal and
      preeclamptic pregnancies.
AB  - OBJECTIVE: The aim of this study was to examine the distribution of endothelin-1
      (ET-1) in the human placenta at different gestational ages and to determine
      whether differences in ET-1 immunoreactivity occurred in preeclamptic compared
      with uncomplicated pregnancies. METHODS: Localization of ET-1 was investigated by
      the immunoperoxidase technique in first-trimester, second-trimester, and term
      human placentas from normal pregnancies and in placentas from preeclamptic
      pregnancies. RESULTS: In normal placentas from all gestational ages studied,
      endothelin-1 immunoreactivity (ET-1 IR) was specifically detected in the
      endothelium of the fetal vessels and in the syncytiotrophoblast. ET-1 IR was also
      expressed by the villous cytotrophoblast of first- and second-trimester normal
      placentas. The extravillous cytotrophoblast of the basal and chorionic plates
      also exhibited ET-1 IR, but with varying degrees of intensity. In preeclamptic
      placentas, the expression of ET-1 IR was uneven with a negative staining in all
      placentas from pregnancies between the 29th and 32nd weeks of gestation. The
      expression of ET-1 IR was most intense in some syncytiotrophoblast tissue in the
      terminal villi after the 33rd week of gestation. In placentas from preeclamptic
      pregnancies between the 35th and the 36th weeks of gestation, strong ET-1 IR
      expression was evident in the endothelium of fetal vessels and in the
      syncytiotrophoblast. Regardless of gestational age, ET-1 IR was also observed in
      the extravillous cytotrophoblast of the basal and chorionic plates of
      preeclamptic placentas. CONCLUSION: This study demonstrates that ET-1 IR is
      widely distributed in the human placenta and provides further evidence to support
      the concept that ET-1 plays an important role as a modulator of vascular tone in
      the uteroplacental and fetoplacental units and may participate in the
      pathogenesis of preeclampsia.

PMID- 12044323
TI  - The classification and diagnosis of the hypertensive disorders of pregnancy:
      statement from the International Society for the Study of Hypertension in
      Pregnancy (ISSHP).

PMID- 12044325
TI  - Changes in vascular reactivity following subrenal aortic constriction in pregnant
      and nonpregnant rats.
AB  - OBJECTIVE: The present study was designed to determine whether or not subrenal
      aortic coarctation (SAC) is able to modify aorta reactivity in pregnant rats.
      METHODS: Wistar female rats were subjected to SAC, and the responses to
      phenylephrine and acetylcholine of aortic segments above (thoracic) and below
      (abdominal) the coarctation from pregnant and non-pregnant rats were explored.
      RESULTS: Contractile responses to phenylephrine and relaxant responses to
      acetylcholine were similar in the thoracic segment from pregnant and non-pregnant
      SAC rats, whereas both kinds of response were higher in the abdominal segment
      from pregnant rats (p < 0.05). L-NAME (a nitric oxide synthase inhibitor)
      increased the effect of phenylephrine only in the aortic rings from pregnant
      animals (p < 0.05) and in general abolished the response to acetylcholine, with
      the exception of the abdominal segment from pregnant rats, in which only a
      partial inhibition was observed (p < 0.05). Indomethacin inhibited the
      contractile response to phenylephrine and increased the relaxant activity to
      acetylcholine in both aortic segments from the two groups of animals (p < 0.05).
      CONCLUSION: The lower contractile response to adrenergic agonists and higher
      relaxant response to acetylcholine that are associated with normal pregnancy are
      lost as a consequence of the coarctation procedure. Changes in the production of
      endothelial nitric oxide and contractile prostanoids appear to be associated with
      the vascular disturbances observed in SAC rats.

PMID- 12044326
TI  - Prorenin concentration in the hypertensive disorders in pregnancy.
AB  - OBJECTIVE: To evaluate the plasma prorenin levels during the three trimesters of
      normal pregnancy, their prognostic value, and their correlation with hypertensive
      disorders of pregnancy. DESIGN: A prospective study in which plasma prorenin and
      renin levels were measured in 55 healthy pregnant women and 66 who developed
      gestational hypertension or preeclampsia. The patients were classified as mild
      preeclampsia (mild PE), severe preeclampsia (severe PE), chronic hypertension and
      superimposed preeclampsia upon chronic hypertension (superimposed PE). METHOD:
      Venous blood samples were collected in the first, second and third trimesters and
      during delivery or cesarean. Plasma renin concentration (PRC) was measured by
      radioinmmunoassay before and after incubation with trypsin solution. The
      difference gave plasma prorenin concentration (PProRC). RESULTS: PRC and PProRC
      were significantly higher in pregnant women compared with healthy non-pregnant.
      PRC was significantly increased in the first trimester in the chronic
      hypertension group and a lower value was found in the first trimester in the
      superimposed PE compared with those in healthy pregnant women. No differences in
      other groups were found. PProRC showed a significant lower value in the first and
      third trimesters in the severe PE group. In the superimposed PE a low value of
      PProRC similar to those of non-pregnant women was found. CONCLUSIONS: The results
      show that the different types of hypertension in pregnancy have different
      profiles of PProRC and PRC in relation to development of preeclampsia. The
      absence of increase of PProRC in the first trimester of superimposed PE may have
      a prognostic value.

PMID- 12044327
TI  - Amino-terminal pro-brain natriuretic peptide in normal and hypertensive
      pregnancy.
AB  - OBJECTIVES: To investigate serum levels of amino-terminal pro-brain natriuretic
      peptide (Nt pro-BNP) as an index of left-ventricular function in normal pregnancy
      and pregnancies complicated by hypertension and also to investigate levels in
      both primigravid and multigravid women. METHODS: Women with hypertension in
      pregnancy (at least two readings of systolic blood pressure > 140 mm Hg and
      diastolic blood pressure > 90 mm Hg) (n = 24) and normotensive women (n = 42)
      were included in the study. Serum Nt pro-BNP was measured using an enzyme-linked
      immunosorbent assay technique. RESULTS: The median serum Nt pro-BNP level in
      pregnancies complicated by hypertension was 420 fmol/L, which was significantly
      greater than that measured in samples obtained from normotensive women in
      pregnancy (340 fmol/L) (p = 0.03). There was a nonsignificant trend toward
      increased levels in proteinuric as compared to nonproteinuric hypertension in
      pregnancy. Multigravida had higher Nt pro-BNP levels (n = 26; median Nt pro-BNP =
      358 fmol/L) than primigravida (n = 16; median Nt pro-BNP = 278 fmol/L) (p = 0.01)
      in association with normal pregnancy. Multigravida also demonstrated a dramatic
      rise in serum Nt pro-BNP levels in association with hypertension in pregnancy (n
      = 13; median Nt pro-BNP = 572 fmol/L) as compared to normal pregnancy (n = 26;
      median Nt pro-BNP = 358 fmol/L) (p = 0.009). CONCLUSION: Serum Nt pro-BNP is
      elevated in women with hypertensive disorders of pregnancy, indicating elevated
      left-ventricular filling pressures. Measured serum levels in both normal and
      hypertensive pregnancy are higher in multigravida than in primigravida.

PMID- 12044328
TI  - Serum antibodies to oxidized low-density lipoprotein in pregnant women with
      preeclampsia and chronic hypertension: lack of correlation with lipid peroxides.
AB  - OBJECTIVES: To evaluate the circulating levels of antibodies to oxidized low
      density lipoprotein (LDL) and their correlation with the lipid peroxide/vitamin E
      ratio in pregnant women with preeclampsia and chronic hypertension. METHODS:
      Antibodies to oxidized LDL were measured by enzyme-linked immunoassay, lipid
      peroxides (malondialdehyde), and vitamin E were measured by high-pressure liquid
      chromatography. Patients were 25 healthy pregnant women, 20 previously
      nonhypertensive women diagnosed with preeclampsia, and 20 women with
      uncomplicated chronic hypertension. RESULTS: Serum levels of antibodies to LDL in
      preeclamptic patients were similar to controls, whereas women with chronic
      hypertension showed a trend for increased mean levels. Lipid peroxides in serum
      were significantly increased and vitamin E levels were significantly decreased in
      preeclampsia with respect to nonhypertensive pregnancy, but no differences were
      observed for chronic hypertensive women. CONCLUSIONS: Our results suggest that
      preeclampsia is not accompanied by increased levels of antibodies to oxidized
      LDL. By contrast, and according to previous studies in nonpregnant patients,
      chronic hypertensive patients showed a trend for elevated levels.

PMID- 12044329
TI  - Matrix metalloproteinase-2 is elevated in the plasma of women with preeclampsia.
AB  - OBJECTIVE: We have recently demonstrated that matrix metalloproteinase-2 (MMP-2)
      alters vascular function through cleavage of vasoactive peptides, resulting in
      increased vasoconstriction and reduced vasodilation. We, therefore, hypothesized
      that MMP levels are increased in women with preeclampsia. In addition, because
      vascular endothelial growth factor (VEGF) has been implicated in the
      pathophysiology of preeclampsia and is involved in angiogenesis that requires the
      release of proteases to allow for migration of endothelial cells, we hypothesized
      that VEGF increases release of MMPs from endothelial cells. METHODS: We used
      zymographic analysis to evaluate MMP-2/MMP-9 levels in plasma of women with
      preeclampsia (n=12) compared to women with uncomplicated pregnancies (n=12). In
      addition, we evaluated the changes in the levels of MMP-2 and MMP-9 as well as
      tissue inhibitors of MMPs (TIMP-1 and TIMP-2) released by cultured human
      umbilical vein endothelial cells in response to VEGF (0.1-10 ng/mL). RESULTS: Our
      data showed that plasma MMP-2 levels were significantly higher in women with
      preeclampsia compared to women with uncomplicated pregnancies (arbitrary
      intensity units: 690 +/-111 and 252 +/-56, respectively, p<0.05). MMP-9 levels
      were below the level of detection. In addition, VEGF stimulated endothelial MMP-2
      and MMP-9 release in a concentration- and time-dependent (6-24 h) manner.
      Moreover, VEGF stimulation of MMP release occurs without significantly affecting
      the release of TIMP-1 and TIMP-2. CONCLUSIONS: These data suggest that VEGF
      promotes secretion of MMPs from endothelial cells that, in turn, could alter
      vascular function in women with preeclampsia.

PMID- 12044330
TI  - Perinatal and maternal outcome following abruptio placentae.
AB  - OBJECTIVE: To characterize the maternal and fetal presentation of abruptio
      placentae and associated maternal and fetal morbidity and mortality by mode of
      delivery and fetal status on admission. STUDY DESIGN: Perinatal data (gestational
      age > 24 weeks) from women with abruptio placentae at a tertiary referral center
      were analyzed. For the purpose of evaluating fetal morbidity and mortality, group
      1 included women with hypertensive disorders of pregnancy (preeclampsia or
      chronic hypertension), PROM, cocaine abuse, and > 20% abruptio placentae without
      regard to fetal status on admission (reassuring, nonreassuring, or stillborn). In
      group 1, either umbilical artery pH < 7.0, Apgar < 3(5), or base excess > 12
      mmol/L represented perinatal hypoxia for this evaluation. Group 2 included women
      with stillborn fetuses on admission without regard to etiology or size of
      abruptio placentae. Comparisons between groups were made with one-way analysis of
      variance, Kruskal-Wallis, or chi2 tests; p < 0.05 was considered significant.
      RESULTS: Group 1 was comprised of 342 women; 58.4% of fetuses had abnormal fetal
      heart rate tracings. Overall, the sensitivity of an abnormal fetal heart rate
      tracing to predict perinatal hypoxia was 87.2%, specificity was 33.9%, positive
      predictive value was 22.2%, and negative predictive value was 92.5%. Of
      parameters suggestive for perinatal hypoxia, 17.3% of neonates had Apgar < 3(5),
      13.0% had umbilical artery pH < 7.0, and 9.9% had base excess > 12 mmol/L.
      Overall, neonatal survival was 84.7%; 12.0% of fetuses were stillborn. For those
      fetuses alive on admission, cesarean delivery was associated with a significant
      reduction in neonatal mortality: odds ratio of 0.10 (95% confidence interval:
      0.05-0.20) and p = 0.0001. Group 2 was comprised of 61 women. Women presenting
      with a stillborn infant on admission were more likely to require transfusions and
      suffer the complications (disseminated intravascular coagulopathy, acute renal
      failure, and acute respiratory distress syndrome) than women presenting with a
      live fetus. CONCLUSION: Cesarean delivery appeared to reduce neonatal mortality.
      Whether emergent cesarean delivery resulted in the birth of compromised fetus
      cannot be evaluated from this study. Composite maternal morbidity is increased
      when a stillborn fetus is present on admission.

PMID- 12044331
TI  - Effect of concentration and biochemical assay on the accuracy of urine dipsticks
      in hypertensive pregnancies.
AB  - OBJECTIVE: To assess how urine concentration and biochemical assay influence the
      assessment of proteinuria. METHODS: This was a prospective study to assess the
      accuracy of detection and quantification of proteinuria within the day assessment
      unit and antenatal ward of a teaching hospital in Leicester, United Kingdom. We
      studied hypertensive pregnancies (of mixed parity) referred to day care
      assessment or attending the antenatal hypertension clinic after 20 completed
      weeks of gestation (n = 197). Aliquots of a well-mixed 24-h urine collection were
      tested by routine dipstick urinalysis and then assayed for protein using the
      Benzethonium Chloride and the Bradford assays (n = 197). MAIN OUTCOME MEASURES:
      Total protein excretion in 24 h and protein concentration per liter of urine for
      both biochemical assays were compared to semiquantitative dipstick protein
      measurement. RESULTS: The prevalence of proteinuria in the study group varied
      according to the method used for testing. Dipstick urinalysis recorded the lowest
      prevalence (16.2%) and the Benzethonium Chloride assay measuring total protein
      excretion in 24 h recorded the highest (70.1%). When the positive and negative
      predictive values for dipstick urinalysis were calculated, performance was found
      to be dependent on both the units of measurement compared and the type of assay
      used as the "gold standard." Positive predictive values ranged from 87.5% to
      96.9% and negative predictive values ranged from 35.2% to 92.1%. CONCLUSIONS: The
      prevalence of proteinuria in hypertensive pregnancies is dependent on the method
      used to detect it. The amount of protein assessed quantitatively is further
      dependent on the biochemical assay employed. However, regardless of the
      quantitative assessment, dipstick urinalysis has a significant false-negative
      rate. This first reporting of a variation in performance between dipstick
      urinalysis and two different biochemical assays in pregnancy may be explained in
      relation to protein assay specificity and the observed protein compositions of
      the samples on electrophoretic analysis. The significance of proteinuria should
      be considered in light of the method used to detect it, but, ultimately, it must
      be related to clinical outcome.

PMID- 12044333
TI  - Vascular maternal reactivity and neonatal size in normal pregnancy.
AB  - OBJECTIVE: The purpose of the present study was to determine the associations of
      cold pressor test (CPT) cardiovascular reactivity with gestational age at birth
      and neonatal size in normotensive pregnant women. METHODS: Seventy (70) healthy
      pregnant women were enrolled. The CPT consisted of introducing the patients'
      hands in cold water (4 degrees C) for 3 min. An automatic oscillometric device
      was used to record blood pressure (BP) every minute for the following 5 min.
      Perinatal results were correlated with CPT findings. RESULTS: Vascular reactivity
      assessed by CPT was higher in pregnant hypertensive women and in women with a
      hypertensive family history. Mean BP increases caused by CPT showed a significant
      negative correlation for gestational age (r = -0.58, p < 0.001) and cephalic
      perimeter (r = -0.57, p = 0.03). Diastolic BP increases caused by CPT were
      negatively correlated with newborn weight (r = -0.78, p < 0.001). Predictable
      newborn weight, gestational age, and cephalic perimeter were 4046 (47 x diastolic
      BP increase), 40.2 (0.07 x mean BP increase), and 35.8 (0.09 x mean BP increase),
      respectively. CONCLUSIONS: Results show that every mm Hg diastolic BP increase in
      response to CPT was correlated with a 47-g decrease in the newborn normal weight.
      Furthermore, every mean mm Hg BP increase in response to CPT was associated with
      a 0.07-week decrease in the newborn normal gestational age and a 0.09-cm decrease
      in the normal cephalic perimeter at birth.

PMID- 12044332
TI  - Mishandling of copper by albumin: role in redox-cycling and oxidative stress in
      preeclampsia plasma.
AB  - OBJECTIVE: To test the hypothesis that enhanced oxidative stress during
      pregnancies complicated by preeclampsia is associated with improper copper (Cu)
      binding by plasma albumin, resulting in enhanced Cu redox-cycling activity and
      that altered Cu binding, in turn, is caused by interactions of excessive amounts
      of free fatty acids with albumin. STUDY DESIGN: We studied binding and redox
      cycling activity of Cu in 17 normal pregnancy and 17 preeclampsia plasma samples.
      Binding of exogenous Cu in plasma samples was quantified indirectly using
      spectrophotometric measurements of its complex with a specific chelator of Cu(I),
      bathocuproine disulfonate. Redox-cycling activity of Cu in plasma samples was
      estimated by electron paramagnetic resonance (EPR) spectroscopy of ascorbate
      radicals formed during one-electron oxidation of ascorbate by redox-active
      catalytic Cu. Formation of Cu/albumin complexes in model systems in the presence
      and absence of fatty acids was studied using EPR spectroscopy of Cu(II)/albumin.
      RESULTS: We found that preeclampsia plasma (as compared to normal pregnancy
      plasma) (1) displays elevated endogenous ascorbate redox-cycling that is
      normalized by a Cu(II) chelator, cuprizone I, (2) has lowered capacity to bind
      and redox-regulate exogenously added Cu, and (3) responds to treatment with fatty
      acid-free albumin by diminished ascorbate oxidizing activity. Conversely,
      addition of free fatty acid (oleic acid) to normal pregnancy plasma sample yields
      increased ascorbate redox-cycling activity. Our model experiments showed that Cu
      dependent redox-cycling activity of purified human serum albumin is significantly
      increased by excess free fatty acids. CONCLUSION: Mishandling of Cu by albumin
      contributes to oxidative stress in preeclampsia. Cu chelators may represent
      promising mechanism-based antioxidants to attenuate oxidative stress in
      preeclampsia.

PMID- 12044334
TI  - The West Midlands "Severe Hypertensive Illness in Pregnancy" (SHIP) audit.
AB  - OBJECTIVE: To study the management of a series of women presenting with acute
      onset hypertension in the 21 maternity units in the West Midlands region, in
      order to measure the standard of care and the outcomes of these patients and
      their babies. DESIGN: Multicenter audit. SETTING: Twenty-one Maternity Units in
      the West Midlands region with 85,658 births during the audit period. METHODS:
      Prospective data collection by named coordinators (multidisciplinary) in each
      unit using customized proformas. The proformas were then forwarded to the
      Research Coordinator for input onto a database and observational analyses.
      RESULTS: The total number of cases was 516. Eighty-one percent were diagnosed as
      having severe preeclampsia, 14% HELLP syndrome, and 5% eclampsia. Seven percent
      were admitted to the intensive therapy unit. Seventy percent of births were
      preterm, 62% of babies were low birth weight (< 2.5 kg), 57% of babies were
      admitted to the neonatal unit, and the perinatal mortality rate was 5%. The
      commonest antihypertensive agents were hydralazine and nifedipine. In terms of
      compliance with audit standards, 61% had both oxygen saturation and noninvasive
      blood pressure monitoring, 47% had good fluid balance documentation, and 79% had
      no fluid mismanagement. Seventy-four percent were seen by a consultant
      obstetrician, 62% were seen by a member of an "expert team," 83% adhered to local
      guidelines, and 71% of eclamptics received magnesium sulfate (MgSO4). CONCLUSION:
      Our study shows that severe hypertensive illness of pregnancy remains an
      important cause of maternal mortality and perinatal mortality. This audit
      highlights areas in which standards of care can be improved.

PMID- 12044335
TI  - Hypertensive disorders in pregnancy: frequency and associated factors in a cohort
      of Brazilian women.
AB  - OBJECTIVE: To evaluate the frequency of and risk factors associated with
      hypertensive disorders in general antenatal care in five distinct areas of
      Brazil. METHODS: We performed a cohort study of 4892 women enrolled in
      midpregnancy from 1991 to 1995. Patients were queried at enrollment about
      hypertension prior to pregnancy. Medical diagnoses of hypertensive disorders in
      pregnancy were abstracted from patient records. Hypertensive disorders in
      pregnancy were classified according to recommendations of the American College of
      Obstetrics and Gynecology (ACOG). RESULTS: Of 4892 women studied, 367 (7.5%)
      presented hypertensive disorders, 113 (2.3%) being preeclampsia/eclampsia and 198
      (4.0%) chronic hypertension. Frequencies of superimposed preeclampsia/eclampsia
      and transitory hypertension were 0.5% and 0.7%, respectively. Greater brachial
      arm circumference was strongly associated both with preeclampsia/eclampsia and
      with chronic hypertension (threefold difference across extreme quartiles, p < or
      =0.001). In adjusted analyses, being older, black, and obese were important and
      statistically significant risk factors for chronic hypertension. Similarly,
      nulliparity was a statistically significant risk factor for
      preeclampsia/eclampsia, and tendencies toward increased risk were seen for older,
      black, and obese women in adjusted analyses. Preeclampsia/eclampsia and chronic
      hypertension were notably less frequent in Manaus, although regional differences
      were statistically significant only for chronic hypertension. CONCLUSIONS:
      Hypertensive disorders commonly complicate pregnancy in Brazilian women. Risk
      factors for these disorders appear similar to those reported in other countries.
      Use of an inappropriately sized cuff to measure blood pressure may result in many
      false-positive diagnoses in more obese women. The considerably lower frequency of
      hypertensive disorders found in Manaus, in the Amazon region, warrants further
      study.

PMID- 12044336
TI  - Does a lean prepregnancy body mass index influence outcome in pregnancies
      complicated by mild preeclampsia remote from term?
AB  - OBJECTIVES: To determine the influence of a lean prepregnancy body mass index
      (BMI) on pregnancy outcome in women with mild preeclampsia. STUDY DESIGN: A
      matched cohort design was used. A total of 99 pregnant women with mild
      preeclampsia and a nonobese prepregnancy BMI (22-28 kg/m2) were matched 1 : 1 for
      gestational age at diagnosis, race, and parity to 99 women with mild
      preeclampsia, but a lean prepregnancy BMI (< or = 20 kg/m2). All patients were
      enrolled in an outpatient management program between 24 and 36 weeks' gestation
      for a minimum of 2 days, had singleton pregnancies, and exhibited proteinuria of
      > or = 1+ at the start of the program. Outpatient monitoring included automated
      blood pressure measurements and daily assessment of weight, proteinuria, and
      fetal movement. RESULTS: The mean gestational age at enrollment was 33.4 +/- 2.8
      weeks for both groups. By matching, 65% of patients in each group were
      nulliparous and 79% of patients in each group were of the white race. There were
      no patients in either group with a history of preterm delivery. The mean
      gestational age at delivery (36.8 +/- 2.3 versus 36.3 +/- 2.3 weeks, p = 0.047)
      was greater in the lean prepregnancy BMI group with a lower cesarean section rate
      (32% versus 52%, p = 0.006) but similar mean birth weights (2728 +/- 698 versus
      2679 +/- 802 g, p = 0.635). There were two perinatal deaths in the lean
      prepregnancy BMI group and one in the nonobese prepregnancy BMI group (p = 1.0).
      CONCLUSION: In patients with mild preeclampsia remote from term, a lean
      prepregnancy BMI was associated with a later gestational age at delivery and a
      reduced incidence of cesarean delivery. Neonatal outcomes, however, did not
      differ significantly between the groups.

PMID- 12044337
TI  - Prothrombin 20210 G: a mutation and Factor V Leiden mutation in women with a
      history of severe preeclampsia and (H)ELLP syndrome.
AB  - OBJECTIVE: The 20210 G-A prothrombin gene variant and the Factor V Leiden
      mutation are mutations associated with venous thrombotic risk. The aim of our
      study was to assess the prevalence of these specific mutations in women with a
      history of preeclampsia or hemolysis elevated liver enzymes, and low platelet
      count [(H)ELLP] syndrome and their influence on perinatal outcome. In addition,
      the association with venous thromboembolism was assessed. METHODS: One hundred
      fourteen (114) women with a history of preeclampsia or (H)ELLP syndrome were
      investigated at least 3 months' postpartum for the presence of 20210 G-A
      prothrombin gene variant and Factor V Leiden mutation. RESULTS: Four (3.5%) of
      the women had the 20210 G-A prothrombin gene variant, four (3.5%) women had the
      Factor V Leiden mutation, and one of these women carried both mutations. The
      prevalence of prothrombin 20210 G-A prothrombin and Factor V Leiden mutation in
      women with severe preeclampsia or (H)ELLP syndrome were comparable with the
      prevalence in the general Dutch population. The odds ratio for thromboembolism
      for carriers versus noncarriers was 22 (95% confidence interval: 1.7-303).
      Perinatal mortality was not significantly higher in women with any mutation [odds
      ratio: 1.5 (0.2-9.5)]. CONCLUSIONS: Although our study confirms that prothrombin
      20210 G-A mutation and Factor V Leiden mutation are important genetic risk
      factors associated with thrombotic risk, these mutations appear not related to
      perinatal outcome in women with preeclampsia or (H)ELLP syndrome. It is unlikely
      that these mutations are of major importance for the development of severe
      preeclampsia or (H)ELLP syndrome.

PMID- 12044338
TI  - Xanthine oxidase activation in mild gestational hypertension.
AB  - OBJECTIVE: We hypothesized that activation of the xanthine oxidase (XO) enzyme
      system is a potential source of free radicals in pregnancy-induced hypertension
      (PIH). METHODS: A prospective observational study was carried out on 16 pregnant
      women who met the criteria of gestational hypertension [rise in blood pressure
      (BP) of 30 mm Hg systolic or 15 mm Hg diastolic after 20 weeks gestation or
      BP>140/90 mm Hg if earlier pressure is unknown] without proteinuria or any signs
      of renal impairment. Fourteen women with a clinically normal pregnancy matched
      for maternal age, parity, and gestational age acted as pregnant controls.
      Nonpregnant control women were members of the laboratory staff ( n=15). MAIN
      OUTCOME MEASURES: Concentrations of free sulfhydryl (SH) groups, purine
      catabolites, lipid peroxidation products in plasma, and blood carboxyhemoglobin
      levels were used to follow oxidative stress and potential hemolysis. A
      noninvasive measurement of functional XO activity was carried out (i.e., the
      urinary ratio of the two metabolites of caffeine was estimated). RESULTS: A
      pronounced oxidative stress was demonstrated in plasma samples of patients with
      hypertension by the elevated concentrations of uric acid and lipid peroxidation
      products. A reduced level of free sulfhydryl groups and an increased
      concentration of hypoxanthine (HX) were shown in normotensive pregnant
      individuals. The XO activity index was substantially higher in overweight
      pregnant subjects with mild hypertension [0.849+/-0.096 ( p<0.01)] than in
      normotensive pregnant women or in age-matched nonpregnant subjects [0.596+/
      0.105, 0.542+/-0.049 (means+/-SD), respectively]. CONCLUSIONS: Our study of
      mildly hypertensive pregnant subjects provides additional evidence of the
      putative role of XO activation as a source of free radicals in the early stage of
      endothelial dysfunction.

PMID- 12044339
TI  - The levels of circulatory cell free fetal DNA in maternal plasma are elevated
      prior to the onset of preeclampsia.
AB  - OBJECTIVE: Elevations in cell free fetal DNA has previously been determined in
      pregnancies affected by preeclampsia. A recent report has indicated that cell
      free fetal DNA concentrations are elevated early in pregnancy before disease
      onset. As we have recently performed a prospective study to examine fetal cell
      traffic in pregnancies at risk for developing preeclampsia, we now quantify cell
      free fetal DNA concentrations in these samples. METHODS: Blood samples were
      collected in the second trimester of pregnancy from pregnancies at risk for
      preeclampsia. Cell free fetal DNA amounts were quantified by real-time PCR. These
      results were then correlated with subsequent pregnancy outcome. RESULTS: Free
      fetal DNA levels were significantly higher (median of 422.9 vs. 128.5 copies/mL
      maternal plasma; p=0.005) in plasma samples from women who developed preeclampsia
      ( n=10) when compared to those who had unremarkable pregnancies ( n=40).
      CONCLUSIONS: Our data independently confirm the finding that maternal plasma cell
      free fetal DNA levels are elevated early in pregnancies, which later develop
      preeclampsia.

PMID- 12044340
TI  - Eclampsia in Sweden.
AB  - OBJECTIVE: Assess the actual rate of eclampsia in Sweden, describe the clinical
      picture of the disease and the maternal and perinatal outcomes. METHODS: Analysis
      of data regarding incidence of eclampsia registered in the Swedish Medical Birth
      Register 1991-1992. The records of all the cases with the diagnosis of eclampsia
      in Sweden during 1991-1992 were retrospectively evaluated regarding maternal and
      fetal outcomes. RESULTS: The incidence of eclampsia after case review was
      3.3/10,000 births. There was no maternal mortality. Severe maternal complications
      occurred in 30%. Recurrent fits were reported in 41%. Antenatal eclampsia was
      usually either not preceded by symptoms or signs of preeclampsia or by just a
      very short period of prodromal symptoms. Among intrapartum and postnatal cases of
      eclampsia, preeclampsia or high blood pressure was more frequently noted when
      convulsions occurred. Perinatal mortality rate was 4/80 (4.7%). Of the infants,
      13% were small for gestational age. CONCLUSION: Compared with earlier studies,
      the incidence of eclampsia has increased significantly. It is questionable
      whether the incidence of eclampsia could be reduced by earlier diagnosis and
      treatment of preeclampsia. The risk of severe complications and recurrent fits
      was substantial, which underlines the importance of adequate treatment of
      eclampsia.

PMID- 12044341
TI  - Linkage and association studies of IL1B and IL1RN gene polymorphisms in
      preeclampsia.
AB  - OBJECTIVE: To determine whether preeclampsia is either associated with or linked
      to two polymorphisms in the IL1B gene (IL1B-TaqI and IL1B-511) and one
      polymorphism in the IL1RN gene (IL1RN-IVS2). METHODS: Genotyping was performed in
      150 affected sib-pair families and 104 healthy Dutch blood donors. Genotype and
      allele frequencies as well as allelic associations were assessed in three groups
      of unrelated women from these 150 families; 133 with either eclampsia,
      preeclampsia or the haemolysis, elevated liver enzymes, low platelets (HELLP)
      syndrome, 101 with preeclampsia only, and 63 with HELLP syndrome only. These
      frequencies were compared to those in controls. Frequencies of transmitted and
      nontransmitted haplotypes, inferred from the three polymorphisms, were compared.
      Allele sharing between affected siblings from all 150 families was assessed by
      means of multipoint nonparametric affected sib-pair analyses. RESULTS: No
      significant differences in genotype and allele frequencies were found between the
      unrelated study groups and controls. No allelic associations were apparent, nor
      were there differences in frequencies of transmitted and nontransmitted
      haplotypes within affected families. Excess allele sharing for any of the three
      polymorphic markers was absent in affected sib-pairs. CONCLUSIONS: None of the
      IL1B and IL1RN polymorphisms provided evidence for either association or linkage
      with the risk for (pre)eclampsia/HELLP syndrome, preeclampsia only or HELLP
      syndrome only.

PMID- 12044342
TI  - Ethene and other biomarkers of oxidative stress in hypertensive disorders of
      pregnancy.
AB  - OBJECTIVE: An increase in reactive oxygen species (ROS) and lipid peroxides and a
      comprised antioxidant status has been implicated in the pathophysiology of severe
      preeclampsia. This study investigates whether oxidative stress and impaired
      antioxidant systems also contribute to milder forms of hypertensive disorders in
      pregnancy. Furthermore, ethene in exhaled air, a noninvasive measure for
      oxidative stress, was evaluated and compared with two other more established
      biomarkers. METHODS: Ethene in exhaled air, plasma protein carbonyls, and the
      ratio of free glutathione/oxidized glutathione (GSHfree/GSHox) as markers for
      oxidative stress as well as the antioxidants vitamins C and E, uric acid,
      glutathione, and the oxygen radical absorbance capacity (ORAC) in plasma were
      measured in 30 healthy nonpregnant, 14 normal pregnant, 9 women with pregnancy
      induced hypertension (PIH), and 14 preeclamptic women. Pregnant participants were
      measured during pregnancy and after delivery. RESULTS: Women suffering from PIH
      and preeclampsia showed higher levels of the antioxidants vitamin E and uric
      acid, and lower levels of vitamin C compared with normal pregnant and nonpregnant
      women. All markers for oxidative stress were comparable between groups. Ethene
      levels showed a positive correlation with protein carbonyls but no correlation
      could be demonstrated with the free glutathione/oxidised glutathione ratio.
      CONCLUSIONS: PIH and preeclampsia are associated with minor alterations in
      antioxidant levels without signs of oxidative stress. Detection of ethene in
      exhaled air seems a promising noninvasive method to study lipid peroxidation but
      further research in more severe preeclampsia is needed.

PMID- 12044343
TI  - Normalization of vasoactive changes in preeclampsia precedes clinical recovery.
AB  - OBJECTIVE: The objective of this study is to compare the serum levels of
      fibronectin, nitric oxide (NO), cyclic guanosine-monophosphate, endothelin-1, and
      6-keto-prostaglandin-F 1alpha in women with and without preeclampsia before and
      after delivery. METHODS: We studied 20 singleton pregnancies complicated by
      preeclampsia, and 20 women undergoing elective cesarean delivery were selected as
      controls. The normalization of circulating concentrations of maternal plasma NO,
      cyclic guanosine-monophosphate, fibronectin, endothelin-1, thromboxane-B 2 and
      renin, and urinary 6-keto-prostaglandin-F 1alpha after delivery was evaluated.
      RESULTS: Mean systolic and diastolic blood pressure (BP) in the puerperium of
      preeclamptic women remained high after discharge from hospital, and only
      circulating fibronectin levels were found to be elevated in affected women at the
      end of hospital stay 5 days after delivery. Normalization of the imbalance in
      vasoactive substances and renal impairment in preeclampsia occur more rapidly
      than the patient's clinical recovery, within 2-3 days postpartum. CONCLUSIONS:
      Slow normalization of circulating fibronectin concentrations reflects slow
      recovery of endothelial damage in preeclampsia, which may play a major role in
      maintaining high BP in the puerperium. Plasma levels of endothelin-1 declined to
      normal levels by the third postpartum day and the finding is consistent with the
      hypothesis that endothelin-1 is not the major vasoconstrictor in the
      pathophysiology of preeclampsia.

PMID- 12044344
TI  - Comparison of Portapres with standard sphygmomanometry in pregnancy.
AB  - BACKGROUND: Continuous beat-to-beat noninvasive blood pressure (BP) measurement
      is possible with Portapres. It constructs finger arterial waveforms beat-to-beat.
      Dedicated software is used to analyze the arterial waveforms. A new technique has
      been developed to reconstruct brachial intra-arterial pressure that uses return
      to flow (RTF). This method has been validated against invasive intra-arterial
      measurements in nonpregnant individuals. OBJECTIVES: To validate Portapres in
      normal and preeclamptic pregnant women against standard aneroid sphygmomanometry
      according to Riva-Rocci-Korotkoff (RRK). METHODS: In 30 normotensive (10 in each
      trimester) and 20 preeclamptic women, two trained observers blinded from each
      other's results took BP measurements with a standard sphygmomanometer. These
      measurements were compared with sequential same-arm averaged measurements
      obtained during 30 sec by Portapres, following protocols from the Association for
      the Advancement of Medical Instrumentation (AAMI, mean accepted difference < or =
      5 mmHg, SD < or = 8) and British Hypertension Society (BHS, gradings A down to
      D). RESULTS: A total of 150 measurement pairs were analyzed. Cumulative
      percentages of absolute pressure differences for all women (BHS) and mean
      pressure differences (SD) for different trimesters and preeclampsia (AAMI)
      between sphygmomanometry and Portapres were calculated. Overall, mean difference
      (SD) for systolic BP was 5 (SD 8) and for diastolic BP was -3 (SD 8), although
      analysis of variance revealed a significant effect for preeclampsia on diastolic
      differences between the two methods of BP measurement ( p<0.001). CONCLUSIONS:
      Portapres with RTF, developed to equal intra-arterial brachial pressure, compares
      reasonably well to RRK and overall meets the criteria set by the AAMI. According
      to the BHS, Portapres receives a B-grading for diastolic BP and a C-grading for
      systolic BP. As Portapres measures BP and calculates cardiac output continuously
      and noninvasively, it would appear worthwhile to further evaluate this device in
      pathological pregnancies.

PMID- 12044345
TI  - Excretion of antihypertensive medication into human breast milk: a systematic
      review.
AB  - OBJECTIVE: To establish which antihypertensive medications are safe for use while
      breastfeeding, by reviewing the available evidence. METHODS: Reports of studies
      examining the transfer of antihypertensive medications to breastmilk were
      identified from multiple MEDLINE and EMBASE searches, manual review of
      bibliographies of articles and textbooks on drug use during lactation. The
      reports were reviewed and the results were compiled. RESULTS: Prospective cohort
      studies and case reports constituted the only available evidence. Compilation of
      these results found that the milk to plasma (M/P) ratios varied widely across the
      beta-blocker family, the beta-blockers with low protein binding having the
      highest M/P ratios. The angiotensin-converting enzyme (ACE) inhibitors,
      methyldopa, and some calcium channel blockers had low M/P ratios. CONCLUSION: The
      available data to date indicate that ACE inhibitors, methyldopa, beta-blockers
      with high protein binding, and some calcium channel blockers all appear to be
      safe treatments of hypertension in a nursing mother. The data suggest that drugs
      to be avoided are beta-blockers with low protein binding. However, the available
      evidence is limited and further studies are needed to confirm these findings.

PMID- 12044346
TI  - DNA methyltransferases get connected to chromatin.
AB  - The DNA methyltransferases (Dnmts) are responsible for the generation of genomic
      methylation patterns, which lead to transcriptional silencing. Recent studies
      have identified new protein partners for the Dnmts revealing novel mechanisms by
      which they can be targeted to specific genomic regions to silence genes. In
      particular, the links identified with histone deacetylases, histone
      methyltransferases and SNF-2-like ATPases are defining new requirements for the
      functioning of Dnmts. A picture is emerging whereby the Dnmts are intimately
      connected to the chromatin environment in which they are working.

PMID- 12044347
TI  - Evidence for cysteine clustering in thermophilic proteomes.
AB  - Through linguistic analysis, we show that the presence of an amino acid at a
      given position within a proteome positively influences the presence of identical
      amino acids at nearby positions. We call this phenomenon 'amino acid clustering'.
      Clustering extends well beyond the closest neighbouring sites and is particularly
      pronounced for cysteine and tryptophan. Cysteine clusters preferentially form
      CXXC structures, and they are often involved in metal coordination or disulfide
      bond formation. Cysteine clustering shows a clear correlation with the growth
      temperature of the organism. This seems to be a general property of living
      organisms.

PMID- 12044348
TI  - Regional similarities in polymorphism in the human genome extend over many
      megabases.
AB  - The human genome exhibits extensive regional variation both in base composition
      and in the synonymous and nonsynonymous substitution rates of protein-coding
      genes. If such regional variation is due to variation in mutation rates, then
      levels of polymorphism should also vary across the human genome. Building on
      recent advances in mapping the human genome, we demonstrate regional variation in
      single nucleotide polymorphism density extending over many megabases. The range
      of local similarity in polymorphism shown by our genome-wide study is similar to
      the range of local similarity in base composition, and occurs over much longer
      distances than the variation in polymorphism revealed by studies of linkage
      disequilibrium.

PMID- 12044349
TI  - Genotype to phenotype: associations, errors and complexity.
AB  - The Keystone Symposium on Genotype to Phenotype: Focus on Disease was held in
      Santa Fe, New Mexico, USA, from 19 to 24 February 2002.

PMID- 12044356
TI  - Cell cycle analysis and microarrays.

PMID- 12044357
TI  - Base composition bias might result from competition for metabolic resources.
AB  - The GC content of bacterial genomes varies from 25 to 75%, but the reason for
      this variation is unclear. Here, we show that genomes of bacteria that rely on
      their host for survival (obligatory pathogens or symbionts) tend to be AT rich.
      Furthermore, we have analysed bacterial phages, plasmids and insertion sequences,
      which might also be regarded as 'intracellular pathogens', and show that they too
      are significantly richer in AT than their hosts. We suggest that the higher
      energy cost and limited availability of G and C over A and T/U could be a basis
      for the understanding of these differences.

PMID- 12044358
TI  - A critical analysis of the role of growth hormone and IGF-1 in aging and
      lifespan.
AB  - Studies in Caenorhabditis elegans demonstrate that disruption of the daf-2
      signaling pathways extends lifespan. Similarities among the daf-2 pathway,
      insulin-like signaling in flies and yeast, and the mammalian insulin-like growth
      factor 1 (IGF-1) signaling cascade raise the possibility that modifications to
      IGF-1 signaling could also extend lifespan in mammals. In fact, growth hormone
      (GH)/IGF-1-deficient dwarf mice do live significantly longer than their wild-type
      counterparts. However, multiple endocrine deficiencies and developmental
      anomalies inherent in these models confound this interpretation. Here, we
      critique the current mammalian models of GH/IGF-1 deficiency and discuss the
      actions of GH/IGF-1 on biological aging and lifespan.

PMID- 12044359
TI  - Model choice in gene mapping: what and why.
AB  - The choice of an appropriate genetic model describing the genetic architecture
      underlying a character of interest is an inherent part of the gene mapping
      studies of human and other living organisms. The genetic model specifies the
      statistical parameters for the number of genes, their positions, and the types
      and magnitudes of their contributions to the phenotype. There are many
      considerations involved in model formulation (choice) ranging from the
      assumptions concerning the data, the role of environment, and the number of
      oligogenes (or quantitative trait loci) influencing the trait behavior. There are
      several model selection procedures and criteria under specific sampling designs
      in the genetic literature. These approaches often have their origin in computer
      science or in general statistical theory. Our aim here is to give an overview of
      the most popular statistical criteria and to present principles behind them.
      Bayesian model averaging is suggested as a robust alternative for such methods.

PMID- 12044360
TI  - Association analysis of candidate genes for neuropsychiatric disease: the
      perpetual campaign.
AB  - Association studies have been proposed to identify the genetic determinants of
      complex neuropsychiatric traits. Although such studies of candidate genes offer
      great potential to identify genetic variants that contribute to the expression of
      psychiatric disease, no consistent associations have been identified. Studies to
      date have focused on candidate genes that are selected for analysis on the basis
      of incomplete information about gene function in the brain, therefore the
      majority of genes expressed in the brain have been ignored. Additionally, most
      genetic determinants of psychiatric disease will probably be of modest effect and
      therefore require association studies of large samples. As genomic technologies
      advance, massive genotyping of large samples should allow identification of
      alleles that contribute to psychopathology.

PMID- 12044361
TI  - Advances in human artificial chromosome technology.
AB  - Human artificial chromosome (HAC) technology has developed rapidly over the past
      four years. Recent reports show that HACs are useful gene transfer vectors in
      expression studies and important tools for determining human chromosome function.
      HACs have been used to complement gene deficiencies in human cultured cells by
      transfer of large genomic loci also containing the regulatory elements for
      appropriate expression. And, they now offer the possibility to express large
      human transgenes in animals, especially in mouse models of human genetic
      diseases.

PMID- 12044362
TI  - How did East German genetics avoid Lysenkoism?
AB  - Lysenkoism gained favour in the Soviet Union during the 1930s and 1940s,
      replacing mendelian genetics. Opponents of Lysenko were dismissed from their
      jobs, imprisoned and, not infrequently, died. After World War II in some of the
      East European Soviet satellite states, Lysenkoism became the official genetics
      supported by the communist authorities, and thus, genetics and biology were set
      back many years. Yet the uptake of Lysenkoism was not uniform in the Eastern
      Bloc. The former East Germany (GDR) mostly escaped its influence, owing to the
      contribution of a few brave individuals and the fact that the country had an open
      border with the West (West Berlin).

PMID- 12044368
TI  - Playing the branding game.

PMID- 12044369
TI  - Sudden death in epilepsy: a wake-up call for management.

PMID- 12044370
TI  - A non-multiresistant community MRSA exposes its genome.

PMID- 12044371
TI  - Fluid restriction for postoperative patients?

PMID- 12044372
TI  - Closing the gap between psychiatric epidemiology and mental health in post
      conflict situations.

PMID- 12044373
TI  - Blunt and penetrating injuries caused by rubber bullets during the Israeli-Arab
      conflict in October, 2000: a retrospective study.
AB  - BACKGROUND: Low-velocity rubber bullets were used by Israeli police to control
      riots by Israeli-Arabs in early October, 2000. We aimed to establish the factors
      that contribute to severity of blunt and penetrating injuries caused by these
      missiles. METHODS: We analysed medical records of 595 casualties admitted. We
      assessed relation of severity of injury to type of bullet, anatomical region of
      injury, and final outcome. Severity of injury was established by the abbreviated
      injury scale, and we calculated injury severity score. FINDINGS: 151 males and
      one female (age range 11-59 years) were included in the study, in whom 201 proven
      injuries by rubber bullets were detected. Injuries were distributed randomly over
      the body surface and were mostly located in the limbs (n=73), but those to the
      head, neck, and face (61), chest (39), back (16), and abdomen (12) were also
      frequently noted. 93 (61%) patients had blunt injuries and 59 (39%) penetrating
      ones. Severity of injury was dependent on ballistic features of the bullet,
      firing range, and anatomic site of impact. Two casualties died after a
      penetrating ocular injury into the brain and one died as a result of
      postoperative aspiration after a knee injury. INTERPRETATION: Resistance of the
      body surface at the site of impact (elastic limit) is the important factor that
      ascertains whether a blunt or penetrating injury is inflicted and its severity.
      Inaccuracy of rubber bullets and improper aiming and range of use resulted in
      severe injury and death in a substantial number of people. This ammunition should
      therefore not be considered a safe method of crowd control.

PMID- 12044374
TI  - Emotional problems in Palestinian children living in a war zone: a cross
      sectional study.
AB  - BACKGROUND: Children living in war zones are at high risk of developing post
      traumatic stress and other emotional disorders, but little is known about the
      effect of traumatic events during war. We aimed to assess the nature and severity
      of emotional problems in Palestinian children whose homes had been bombarded and
      demolished during the crisis in Palestine, compared with children living in other
      parts of the Gaza strip. METHODS: 91 children exposed to home bombardment and
      demolition during Al Aqsa Intifada and 89 controls who had been exposed to other
      types of traumatic events related to political violence completed self-report
      measures of post-traumatic stress, anxiety, and fears. FINDINGS: Significantly
      more children exposed to bombardment and home demolition reported symptoms of
      post-traumatic stress (p=0.0008) and fear (p=0.002) than controls. 54 (59%) of 91
      exposed children and 22 (25%) of 89 controls reported post-traumatic stress
      reactions of clinical importance. Exposure to bombardment was the strongest
      socioeconomic predictor of post-traumatic stress reactions (odds ratio 0.25 [95%
      CI 0.12-0.53], p=0.0008). By contrast, children exposed to other events, mainly
      through the media and adults, reported more anticipatory anxiety and cognitive
      expressions of distress (p=0.001) than children who were directly exposed.
      INTERPRETATION: Children living in war zones can express acute distress from
      various traumatic events through emotional problems that are not usually
      recognised. Health professionals and other agencies coming in contact with
      children who have been affected by war and political violence need to be trained
      in detection and treatment of such presentations.

PMID- 12044375
TI  - Early revascularisation and 1-year survival in 14-day survivors of acute
      myocardial infarction: a prospective cohort study.
AB  - BACKGROUND: Randomised trials of early revascularisation in acute coronary
      syndromes have yielded conflicting results with respect to effects on survival.
      We assessed the association between revascularisation within 14 days after the
      index event and 1-year mortality in individuals who survived for at least 14 days
      after an acute myocardial infarction. METHODS: We studied a prospective cohort of
      patients admitted to the coronary care units of 61 Swedish hospitals between 1995
      and 1998. We obtained 1-year mortality data from the Swedish National Cause of
      Death Register. We assessed 21,912 individuals with first registry-recorded acute
      myocardial infarction, who were younger than age 80 years, and alive at day 14.
      Relative risk of 1-year mortality in patients who had revascularisation (n=2554)
      or those who did not (n=19,358) within 14 days was calculated by Cox regression
      analysis, adjusting for multiple covariates that affect mortality and with a
      propensity score that adjusted for covariates that affected the likelihood of
      early revascularisation. FINDINGS: At 1 year, unadjusted mortality was 9.0% (1751
      deaths) in the conservative group and 3.3% (84 deaths) in the early
      revascularisation group. In the Cox regression analysis early revascularisation
      was associated with a reduction in 1-year mortality (relative risk 0.47; 95% CI
      0.37-0.60; p<0.001). This relative reduction of mortality was similar in all
      subgroups irrespective of age, sex, baseline characteristics, previous disease
      manifestations, or treatment. INTERPRETATION: Early revascularisation in
      individuals with acute myocardial infarction is associated with substantial
      reduction in 1-year mortality. Our findings lend support to the use of an
      invasive approach early after an acute myocardial infarction.

PMID- 12044376
TI  - Effect of salt and water balance on recovery of gastrointestinal function after
      elective colonic resection: a randomised controlled trial.
AB  - BACKGROUND: Low concentrations of albumin in serum and long gastric emptying
      times have been returned to normal in dogs by salt and water restriction, or a
      high protein intake. We aimed to determine the effect of salt and water balance
      on recovery of gastrointestinal function after elective colonic resection in
      human beings. METHODS: We randomly allocated ten patients to receive
      postoperative intravenous fluids in accordance present hospital practice (> or =
      3 L water and 154 mmol sodium per day) and ten to receive a restricted intake (<
      or = 2 L water and 77 mmol sodium per day). All patients had no disease other
      than colonic cancer. The primary endpoint was solid and liquid-phase gastric
      emptying time, measured by dual isotope radionuclide scintigraphy on the fourth
      postoperative day. Secondary endpoints included time to first bowel movement and
      length of postoperative hospital stay. Analysis was by intention to treat.
      FINDINGS: Median solid and liquid phase gastric emptying times (T(50)) on the
      fourth postoperative day were significantly longer in the standard group than in
      the restricted group (175 vs 72.5 min, difference 56 [95% CI 12-132], p=0.028;
      and 110 vs 73.5 min, 52 [9-95], p=0.017, respectively). Median passage of flatus
      was 1 day later (4 vs 3 days, 2 [1-2], p=0.001); median passage of stool 2.5 days
      later (6.5 vs 4 days, 3 [2-4], p=0.001); and median postoperative hospital stay 3
      days longer (9 vs 6 days, 3 [1-8], p=0.001) in the standard group than in the
      restricted group. One patient in the restricted group developed hypokalaemia,
      whereas seven patients in the standard group had side-effects or complications
      (p=0.01). INTERPRETATION: Positive salt and water balance sufficient to cause a 3
      kg weight gain after surgery delays return of gastrointestinal function and
      prolongs hospital stay in patients undergoing elective colonic resection.

PMID- 12044377
TI  - Tumoral calcinosis.

PMID- 12044378
TI  - Genome and virulence determinants of high virulence community-acquired MRSA.
AB  - BACKGROUND: A new type of meticillin-resistant Staphylococcus aureus (MRSA),
      designated community-acquired MRSA, is becoming increasingly noticeable in the
      community, some strains of which cause fatal infections in otherwise healthy
      individuals. By contrast with hospital-acquired MRSA, community-acquired MRSA is
      more susceptible to non b-lactam antibiotics. We investigated the high virulence
      potential of certain strains of this bacterium. METHODS: We ascertained the whole
      genome sequence of MW2, a strain of community-acquired MRSA, by shotgun cloning
      and sequencing. MW2 caused fatal septicaemia and septic arthritis in a 16-month
      old girl in North Dakota, USA, in 1998. The genome of this strain was compared
      with those of hospital-acquired MRSA strains, including N315 and Mu50. FINDINGS:
      Meticillin resistance gene (mecA) in MW2 was carried by a novel allelic form
      (type IVa) of staphylococcal cassette chromosome mec (SCCmec), by contrast with
      type II in N315 and Mu50. Type IVa SCCmec did not carry any of the multiple
      antibiotic resistance genes reported in type II SCCmec. By contrast, 19
      additional virulence genes were recorded in the MW2 genome. All but two of these
      virulence genes were noted in four of the seven genomic islands of MW2.
      INTERPRETATION: MW2 carried a range of virulence and resistance genes that was
      distinct from those displayed on the chromosomes of extant S aureus strains. Most
      genes were carried by specific allelic forms of genomic islands in the MW2
      chromosome. The combination of allelic forms of genomic islands is the genetic
      basis that determines the pathogenicity of medically important phenotypes of S
      aureus, including those of community-acquired MRSA strains.

PMID- 12044379
TI  - Antibiotics for weight loss, osteolysis, hepatic and adrenal tumours.

PMID- 12044380
TI  - Carriage of serogroup C meningococci 1 year after meningococcal C conjugate
      polysaccharide vaccination.
AB  - The UK was the first place to introduce meningococcal serogroup C conjugate (MCC)
      vaccines. From November, 1999, all people younger than 18 years, about 14 million
      individuals, were offered MCC immunisation. The uptake rate was more than 70% by
      November, 2000. We compared the carriage of meningococci in isolates we obtained
      from 14,064 students aged 15-17 years during vaccination in 1999, with those from
      16,583 students of the same age surveyed 1 year later. Carriage of serogroup C
      meningococci was reduced by 66% (p=0.004). Our results show that MCC vaccines
      protect against carriage of meningococci that express serogroup C polysaccharide
      capsules.

PMID- 12044381
TI  - Expression of 25-hydroxyvitamin D-1-alpha-hydroxylase mRNA in individuals with
      colorectal cancer.
AB  - Vitamin D prevents proliferation, promotes differentiation, and induces apoptosis
      of colon cells, and reduced intake or insufficiency of the vitamin in the body
      are associated with increased risk of colorectal cancer. Results of previous
      studies have suggested that mRNA that codes for 25-hydroxyvitamin D-1-alpha
      hydroxylase (1 alpha OHase), which converts 25-hydroxyvitamin D to its active
      metabolite, might be up regulated in human colon carcinomas. We used real-time
      reverse transcription PCR assays to measure absolute 1 alpha OHase mRNA
      concentrations in the colonic mucosa of 44 individuals without cancer, and in
      paired healthy colon and cancerous colon samples taken from 27 individuals with
      the disease, to ascertain whether or not such up regulation takes place. Our
      results suggest that concentrations of 1 alpha OHase mRNA in tumour samples and
      in healthy colon samples from individuals without cancer are similar, but that
      concentrations are significantly lower in the paired, phenotypically healthy
      mucosa of individuals with cancer.

PMID- 12044382
TI  - Persistence of dual-tropic HIV-1 in an individual homozygous for the CCR5 Delta
      32 allele.
AB  - Entry of HIV-1 into a cell happens only after viral envelope glycoproteins have
      bound to CD4 and a chemokine receptor. Generally, macrophage-tropic strains use
      CCR5, and T cell-line-tropic strains use CXCR4 as coreceptors for virus entry.
      Dual-tropic viruses can use both CCR5 and CXCR4. About 1% of white people are
      homozygous for a non-functional CCR5 allele, containing a 32 base pair deletion
      (CCR5 Delta 32). We studied the persistence of dual-tropic HIV-1 in an individual
      homozygous for this deletion. Our results suggest that structural features of the
      HIV-1 envelope linked to CCR5 tropism could confer a selective advantage in vivo.

PMID- 12044387
TI  - Croatia restructures its emergency medicine system.

PMID- 12044383
TI  - Advances highlighted at US cancer meeting.

PMID- 12044389
TI  - Canadian Parliament finally agrees human reproduction research act.

PMID- 12044390
TI  - Ethics group advises caution before EC issues stem-cell line patents.

PMID- 12044391
TI  - North Korea's healthy facade hides dying nation.

PMID- 12044392
TI  - Pathogenesis of bone fragility in women and men.
AB  - There is no one cause of bone fragility; genetic and environmental factors play a
      part in development of smaller bones, fewer or thinner trabeculae, and thin
      cortices, all of which result in low peak bone density. Material and structural
      strength is maintained in early adulthood by remodelling; the focal replacement
      of old with new bone. However, as age advances less new bone is formed than
      resorbed in each site remodelled, producing bone loss and structural damage. In
      women, menopause-related oestrogen deficiency increases remodelling, and at each
      remodelled site more bone is resorbed and less is formed, accelerating bone loss
      and causing trabecular thinning and disconnection, cortical thinning and
      porosity. There is no equivalent midlife event in men, though reduced bone
      formation and subsequent trabecular and cortical thinning do result in bone loss.
      Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes
      hyperparathyroidism secondary to calcium malabsorption increases remodelling,
      worsening the cortical thinning and porosity and predisposing to hip fractures.
      Concurrent bone formation on the outer (periosteal) cortical bone surface during
      ageing partly compensates for bone loss and is greater in men than in women, so
      internal bone loss is better offset in men. More women than men sustain fractures
      because their smaller skeleton incurs greater architectural damage and adapts
      less effectively by periosteal bone formation. The structural basis of bone
      fragility is determined before birth, takes root during growth, and gains full
      expression during ageing in both sexes.

PMID- 12044393
TI  - Iatrogenic adrenergic crisis.

PMID- 12044394
TI  - HIV prevention before HAART in sub-Saharan Africa.
AB  - Data on the cost-effectiveness of HIV prevention in sub-Saharan Africa and on
      highly active antiretroviral therapy (HAART) indicate that prevention is at least
      28 times more cost effective than HAART. We aim to show that funding HAART at the
      expense of prevention means greater loss of life. To maximise health benefits,
      the next major increments of HIV funding in sub-Saharan Africa should be devoted
      mainly to prevention and to some non-HAART treatment and care. Funds should be
      allocated to HAART primarily for demonstration projects that will help prepare
      for scaled-up HAART provision following broad population coverage by prevention
      programmes. UNAIDS and the London School of Hygiene and Tropical Medicine
      recently estimated that at least US $9.2 billion annually is required to mount an
      appropriate response to the HIV pandemic, including substantial funding for
      HAART. To date, US $1.96 billion has been committed to the newly-established UN
      Global Fund to Fight AIDS, Tuberculosis, and Malaria. It is a moral imperative
      that expanded programmes to control HIV be implemented without delay, and that
      the goal of US $9.2 billion or more in annual spending be attained as rapidly as
      possible. The findings and recommendations of this analysis pertain to the
      phasing in of additional HIV-related activities during the current period of
      improved but inadequate funding.

PMID- 12044395
TI  - Effective clinical innovation: an ethical imperative.

PMID- 12044396
TI  - Health toll of the Middle East crisis.

PMID- 12044397
TI  - Health toll of the Middle East crisis.

PMID- 12044398
TI  - Health toll of the Middle East crisis.

PMID- 12044399
TI  - Health toll of the Middle East crisis.

PMID- 12044400
TI  - Health toll of the Middle East crisis.

PMID- 12044401
TI  - Health toll of the Middle East crisis.

PMID- 12044402
TI  - Health toll of the Middle East crisis.

PMID- 12044403
TI  - Health toll of the Middle East crisis.

PMID- 12044404
TI  - Microchimerism from a dizygotic twin in juvenile ulcerative lichen planus.

PMID- 12044405
TI  - Waking the dead.

PMID- 12044406
TI  - Waking the dead.

PMID- 12044407
TI  - Drug resistance and influenza pandemics.

PMID- 12044408
TI  - Apolipoproteins and prediction of fatal myocardial infarction.

PMID- 12044410
TI  - Apolipoprotiens and prediction of fatal myocardial infarction.

PMID- 12044411
TI  - Predicting the failure of amyloid-beta vaccine.

PMID- 12044412
TI  - Safety concerns about kava.

PMID- 12044413
TI  - Occupational medicine at stake in Italy.

PMID- 12044414
TI  - Stigma of mental illness in Japan.

PMID- 12044415
TI  - Mescaline use for 5700 years.

PMID- 12044420
TI  - A dentrificator's relic.

PMID- 12044423
TI  - New prostheses for use in bypass grafts with special emphasis on polyurethanes.
AB  - Vascular bypass procedures using traditional prosthetic grafts such as
      polytetrafluoroethylen (PTFE) and polyethylene tetraphthlate (Dacron) are prone
      to failure when used in low flow states such as in below knee bypass and when the
      diameter of the graft is less than 6 mm. A major factor in this is compliance
      mismatch between the graft and the diseased vessel, which may cause intimal
      hyperplasia at the distal anastomosis. PTFE and Dacron are rigid grafts with poor
      compliance. By improving the compliance of the prosthetic graft it is hoped that
      patency will improve. Recent advances in polyurethane chemistry have developed
      materials that do not degrade and which allow compliance matching of the graft to
      the patient's vasculature. It is now possible to manufacture biologically and
      haemodynamically compatible grafts with small diameter from these polyurethane
      graft materials. This review will focus on the lack of compliance in current
      vascular bypass grafts and the promise of the new polyurethane polymers in a new
      generation of small-bore bypass grafts.

PMID- 12044424
TI  - On the shoulders of giants.

PMID- 12044425
TI  - Inflammatory components in endarterectomy lesions: an immunohistological study.
AB  - The aim of this study was to characterize the immunohistological components of
      chronic inflammation in endarterectomy lesions. Therefore, in 24 patients
      endarterectomy specimens were obtained from coronary arteries during CABG surgery
      (16 from RCA and 8 from LCA) and immunohistologically analyzed using avidin
      biotin method (LSAB(R)/AP) with monoclonal antibodies. Macrophages and CD3
      lymphocytes were counted under 200x magnification but MHC class II and ICAM-1
      adhesion molecules were analyzed semi-quantitatively (scale from 0 to 3+). The
      mean macrophages density was 47.8+/-9.8 cells per mm2 and mean CD3 lymphocyte
      density was 1.3+/-0.6 cells per mm2. Lack or weak expression of HLA-DR (0-1+) on
      macrophages was found in 17 of 24 cases (70.8%). In the remaining seven cases
      (29.2%) there was a moderate and strong expression (2+ and 3+) of HLA-DR
      antigens. Similarly, no or weak ICAM-1 expression on macrophages was detected in
      19 cases (79.2%). These cells were positively stained for ICAM-1 in only five
      cases (20.8%). Our data suggest that in advanced primary atherosclerotic lesions
      chronic inflammation is still present. On the other hand, the small number of
      activated inflammatory cells and the absence of positively stained endothelium
      suggests that inflammatory process tends to be burnt-out.

PMID- 12044426
TI  - Recognition of a non-recurrent laryngeal nerve during carotid endarterectomy.
AB  - Cranial nerve injury during carotid endarterectomy (CEA), while infrequent, may
      have serious consequences. The recurrent laryngeal nerve is one of the most
      commonly injured cranial nerves. Fortunately, most of these injuries are
      temporary. Anatomic variations in the position of cranial nerves present
      challenges to surgeons during CEA. Although the occurrence of a non-recurrent
      laryngeal nerve (NRLN) is rare, proper recognition of this anatomic variation is
      critical in order to minimize complications. We present a case in which a NRLN
      was discovered intraoperatively and carefully preserved.

PMID- 12044427
TI  - Transposed saphenous vein arteriovenous fistula revisited: new technology for an
      old idea.
AB  - Patients without renal function are living longer than in the past, and the
      provision of dialysis access is a growing problem. The distal end of the greater
      saphenous vein can be anastomosed to the femoral artery, creating a transposed
      saphenous vein thigh arteriovenous fistula, which offers the theoretical
      advantages of autologous conduit and a native venous 'anastomosis.' This is a
      rarely performed procedure, however, in part because of the morbidity of vein
      harvest and the risk of groin infection. We have been favorably impressed by the
      reduction in morbidity and wound infection following endoscopic vein harvest for
      lower extremity bypass, and believe that the success of this technique merits a
      reevaluation of this procedure.

PMID- 12044428
TI  - Surgical management of left ventricular aneurysms by endoventricular pericardial
      patch plasty.
AB  - BACKGROUND: Early and late surgical outcomes of endocardial resection and
      aneursymectomy repaired with an autologous pericardial patch were studied.
      METHODS: We studied 125 patients who underwent endoaneurysmorrhaphy with
      pericardial patch during the period from June 1993 until June 2000. Preoperative,
      early and late postoperative results, annual postoperative echocardiography of
      all patients and hemodynamic controls of 35 patients within a mean follow-up of
      64+/-8 months were analyzed. RESULTS: Mean NYHA improved to postoperative 2.1+/
      0.5 from preoperative 2.8+/-0.4. Mean number of bypass grafts was 2.6+/-1.1. Left
      ventricular ejection fraction rate improved to 36.2+/-8% in one month, 39.3+/-9%
      in 6 months, 42.3+/-8% in one year versus preoperative 29.2+/-9% (P< or
      =0.05).Perioperative mortality was 6.4% (eight patients) and 11 deaths were
      observed in the late follow-up (9.4%). CONCLUSION: Endoaneurysmorrhaphy with
      pericardial patch may be an alternative option in the management of left
      ventricular aneurysms within acceptable surgical results.

PMID- 12044429
TI  - Predictors of nephrological morbidity after coronary artery bypass surgery.
AB  - AIM: The aim of this study was to analyse the nephrological morbidity after
      myocardial revascularization. METHODS AND RESULTS: We analysed the pre- per and
      postoperative data of 3815 patients who underwent a primary isolated coronary
      bypass grafting between January 1987 and December 1995. Nephrological
      complications were divided into renal dysfunction and requiring dialysis. The
      increase in nephrological complications (1.2-4%) is the result of an increase of
      patients with renal dysfunction. Unifactorial risk analysis identified age,
      diabetes, hypertension, nephrological pathology, perfusion time, aortic cross
      clamp time, emergency operation and perioperative myocardial infarction as risk
      factors. Multifactorial risk analysis identified age, diabetes, hypertension,
      nephrological pathology, perfusion time, perioperative myocardial infarction and
      the cohorts operated upon in 1990-92, 1993-95 as independent risk factors for
      renal dysfunction, and age, nephrological pathology and perioperative myocardial
      infarction for those needing dialysis. CONCLUSION: Several variables have been
      identified as risk factors for nephrological complications; especially important
      are pre-existing nephrological pathology and perioperative myocardial infarction.

PMID- 12044430
TI  - Low preoperative HSP70 atrial myocardial levels correlate significantly with high
      incidence of postoperative atrial fibrillation after cardiac surgery.
AB  - PURPOSE OF THE STUDY: Atrial fibrillation after cardiac surgery is still a
      frequent encountered complication and has been associated with increased hospital
      length of stay and numerous postoperative complications. The pathogenesis of
      atrial fibrillation involves an overall sequence of perioperative events,
      collectively termed as ischemia-reperfusion injury. Heat-shock proteins have been
      found to provide increased protection during ischemia-reperfusion as well as
      increased postischemic cardiac functional recovery. We sought to determine
      whether preoperative atrial heat shock levels were correlated with the appearance
      of postoperative atrial fibrillation. BASIC METHODS: Preoperative atrial
      myocardial samples obtained just before cannulation from 101 patients were used
      to detect immunohistochemically the expression of heat-shock proteins. The
      derived results were compared statistically with the incidence of postoperative
      atrial fibrillation, its time of appearance, duration and resistance to
      administered antiarrhythmics. PRINCIPAL FINDINGS: The overall incidence of
      postoperative atrial fibrillation was 22.3%. Of these patients, 58.3% had no
      detectable heat shock proteins in their cytoplasm, in sharp contrast with 100% of
      the patients with no atrial fibrillation who were positive for heat shock
      proteins (p<0.01). Four percent of our patient group had prolonged atrial
      fibrillation (defined as duration >48 h). These patients had significantly less
      (p<0.01) nuclear heat shock protein expression compared with the non-atrial
      fibrillation group. However, the difference of the heat shock protein expression
      between the prolonged atrial fibrillation and the rest of the atrial fibrillation
      patients was not significant (p=0.891). CONCLUSIONS: Our results indicate that
      patients with low preoperative atrial heat shock protein expression have a
      significantly greater incidence of postoperative atrial fibrillation. Heat shock
      protein expression did not, however, correlate with the onset of atrial
      fibrillation and the resistance to administered medications. Heat shock protein
      preoperative induction as a measure of myocardial preconditioning may potentially
      decrease the incidence of postoperative atrial fibrillation.

PMID- 12044431
TI  - Stentless aortic valve replacement in elderly patients.
AB  - OBJECTIVE: Seven-year clinical and hemodynamic results of the Cryolife O'Brien
      (CLOB) stentless bioprosthesis in elderly patients are reported. METHODS: From
      1993 to 2000, 36 patients aged >75 years had a CLOB implanted in the aortic
      position. Eighteen (50%) were male. All patients were monitored with serial
      echocardiograms performed preoperatively, at discharge, six months, one year and
      yearly thereafter. RESULTS: The 30-day mortality was 2.4% (1/36). Actuarial
      survival at one, five and seven years were 96.7+/-1.5, 94.8+/-2.0 and 94.8+/
      2.0%, respectively. Peak and mean gradients (PG and MG) reduced and effective
      orifice area index (EOAI) increased over time (P<0.001). Left ventricular mass
      index (LVMI) reduced by 32 g/m2 at discharge (P<0.001) and by 33 g/m2 at six
      months (P<0.001) without further significant changes. CONCLUSIONS: In our series
      CLOB xenograft resulted to be a satisfactory valve substitute in elderly
      patients.

PMID- 12044432
TI  - Mid-term follow-up in patients with Biocor porcine bioprostheses.
AB  - BACKGROUND: Prosthetic cardiac valves have increased life expectancy of patients
      (pts) with valvular heart disease. Bioprosthetic complications required devices
      replacements within 10 years of implantation; structural valve deterioration
      (SVD) has emerged as the major cause of reoperation. We reviewed survival and
      prosthetic complications of Biocor porcine bioprostheses implanted in mitral,
      aortic and mitro-aortic position. METHODS: Between January 1991 and January 2001
      446 pts (192 males; 254 females; mean age 73.4+/-6.7 year, range 40-91) received
      258 aortic, 138 mitral and 50 mitro-aortic Biocor porcine valves; of these 83 pts
      have previous different types of prosthetic devices (15 aortic, 53 mitral and 15
      double). Concomitant cardiac procedures, namely myocardial revascularization,
      were performed in 91/446 pts (20.5%). All explanted bioprostheses (BPS) were
      available for pathologic investigation. Follow-up included 1319 pt.-years and was
      98% complete with a median time of 36 pt.-months. RESULTS: Perioperative
      mortality was 6.8% (30/446 pts; 12 aortic, 17 mitral and 1 double) and was mostly
      related to reoperations. At the end of follow-up 18.5% of pts died (77/416), 12
      deaths were valve-related with freedom from valve related mortality of 94% at 9
      years. Survival was 54% at 9 years. It was 63%, 41% and 62% for aortic, mitral
      and double valve replacement, respectively. At follow-up 87% of pts. were in NYHA
      I-II class and 13% were in III-IV class; 55% were in sinus rhythm, 36% in atrial
      fibrillation and 9% had a pace-maker. Eighty-five percent of pts were
      anticoagulated. There were 6 thromboembolic and 5 anticoagulant-related
      haemorrhagic episodes with no significant difference between aortic and mitral
      position (p=0.7). The event freedom was respectively 92% and 98.5% at 9 years.
      Prosthetic valve endocarditis (PVE) and non-SVD freedom were 96% and 93% at 9
      years. SVD due to tissue degeneration, calcification and cusp's tears affected 2
      pts with 94% freedom at 9 years. Overall freedom from all valve-related
      complications was 80% at 9 years and freedom from reoperation was 92% at 9 years.
      CONCLUSIONS: (1) Our intermediate-term follow-up of the Biocor porcine valve
      (BPS) showed excellent durability in all positions. (2) The aortic patients and
      especially the oldest group had better results than the mitral patients (41% vs.
      63% 9 years survival, p=0.0004). (3) Higher mitral risk was related to higher
      prevalence of reoperations. (4) The incidence of anticoagulation-related
      complications is low in both aortic and mitral position without significant
      difference (p=0.7). 4) A longer follow-up is required to get more information
      about SVD timing.

PMID- 12044433
TI  - Heparin reversal in off-pump coronary artery bypass surgery: complete, partial,
      or no reversal?
AB  - Several clinical studies have reported that avoiding cardiopulmonary bypass
      reduces postoperative bleeding. The purpose of this study is to verify that
      protamine during off-pump coronary artery bypass surgery produces significant
      reduction of postoperative bleeding. Sixty consecutive patients undergoing off
      pump coronary artery bypass surgery were prospectively randomized in three
      groups: Group A received 1 mg of protamine every 100 IU of heparin, Group B 0.5
      mg of protamine every 100 IU of heparin, and Group C none. The three groups were
      analyzed for differences in preoperative cardiac function, pre-, intra-, and
      postoperative coagulation profile, intraoperative variables, and postoperative
      bleeding. In the three study groups, no statistically significant difference was
      found in preoperative cardiac function, pre- and intraoperative coagulation
      profile, and prothrombin time, activated partial thromboplastin time, platelet
      count in the first postoperative day. In Group A, total postoperative bleeding,
      use of packed red blood cells, and mild pericardial effusion prevalence at
      discharge were significantly lower only when compared to Group C, but they were
      not significantly different when compared to Group B. In off-pump coronary artery
      bypass surgery, heparin should be reverted with protamine, otherwise the
      postoperative bleeding risk might increase. Partial heparin reversal might not
      increase postoperative bleeding risk, but it may reduce dose-dependent protamine
      adverse effects.

PMID- 12044434
TI  - A comparison between ischemic preconditioning, intermittent cross-clamp
      fibrillation and cold crystalloid cardioplegia for myocardial protection during
      coronary artery bypass graft surgery.
AB  - The aim of this study was to compare ischemic preconditioning (IPC) with two
      established methods of myocardial protection, namely cold crystalloid
      cardioplegia and intermittent cross-clamp fibrillation (ICCF), in coronary artery
      bypass graft (CABG) surgery. This was a prospective randomised study. Thirty CABG
      patients were randomised to receive: (a) St Thomas' cardioplegia solution no. 2;
      (b) ICCF; or (c) IPC (two 3-min periods of ischemia with 2-min of reperfusion).
      Surgery was performed under standardised conditions by one surgeon (WBP). The
      primary endpoint was cardiac troponin T release during the first 72 h after
      surgery. Mean troponin T at 72 h was significantly lower in the IPC group (0.5
      microg/l; p=0.05, ANOVA) compared with the cardioplegia and ICCF groups (2.1 and
      1.3 microg/l respectively). This suggests that ischemic preconditioning is
      superior at limiting myocardial necrosis during CABG, but there is no difference
      between cold crystalloid cardioplegia and intermittent cross-clamp fibrillation.

PMID- 12044435
TI  - Early reoperation for iatrogenic left main stenosis after aortic valve
      replacement: a perilous situation.
AB  - BACKGROUND: Iatrogenic left main coronary artery (LMCA) stenosis secondary to
      direct ostial cannulation during aortic valve replacement still occurs and is a
      morbid situation due to the difficulties of early reoperation and in providing
      adequate myocardial protection. METHODS: A retrospective analysis was performed
      and identified seven patients with an iatrogenic LMCA stenosis, after 2158 aortic
      valve replacements (AVR) (0.3%) in our institution since 1987. RESULTS: All
      patients with LMCA stenosis after AVR had undergone direct ostial cannulation
      with self-inflating balloon cannulas at the time of AVR. At reoperation for LMCA
      stenosis, severe ischemia developed in one patient and injury to cardiac
      structures occurred in four patients. Four patients suffered a perioperative
      myocardial infarction and congestive heart failure developed in two patients at
      late follow-up. CONCLUSIONS: LMCA stenosis following coronary ostial cannulation
      at the time of AVR is a rare yet morbid complication. Reoperation for this
      condition is fraught with a high operative morbidity rate and poor long-term
      outcome. Prevention of this complication is quintessential, avoiding ostial
      cannulation with self-inflating balloons.

PMID- 12044436
TI  - Carney's syndrome: complex myxomas. Report of four cases and review of the
      literature.
AB  - Cardiac myxomas are rare tumors. They usually appear as a sporadic isolated
      condition in the left atrium of middle-aged women with no other coincidental
      pathology. Carney and others have described in young people a special complex
      group of cardiac myxomas associated to a distinctive complex pathology, giving
      identity to the "Syndrome Myxoma" or "Carney's Syndrome". Four additional cases
      of this syndrome, treated from 1977 to 1999 at the Hospital Clinico de la
      Universidad de Chile are presented here with a comprehensive review of the
      literature, accumulating 100 cases. The main features of our cases include the
      presence of malignant non cardiac tumors, a familial trend, follow-up of 23 years
      and an iterative recurrence in the elder case. To date all patients are tumor
      free. Reviewing the literature, patients with Carney's Syndrome were younger,
      with a mean age of 26 years and female predominance (62%). Cardiac myxomas
      affected the four chambers of the heart: 64% the left atrium; 44% the right
      atrium; 14% the left ventricle and 12% the right ventricle. They were multiple
      tumors in 41% and involved more than one chamber in 31%, being synchronous or
      metachronous. There was a marked familial trend (52%), a high incidence of
      recurrence (20%), with more than one occurring in half the cases. Extra-cardiac
      involvement consisted of: 68% pigmented skin lesions, 40% cutaneous myxomas, 37%
      adrenal cortical disease, 27% myxoid mammary fibroadenoma and 34% male patients
      with testes tumors. A low percentage had pituitary adenoma, melanotic schwannomas
      and thyroid disease. The diagnosis is made when two or more of these criteria are
      present. In agreement with these findings the four chambers of the heart should
      be examined at surgery for atypical myxoma locations, right atriotomy and
      combined superior-transseptal approach improve exposure of the cavities, careful
      screening of the first degree family members should be conducted, and closed
      short and long term follow up controls are important. Complex myxoma appears as a
      multi-systemic disorder, occasionally having an ominous prognosis and malignant
      potentiality, and is still undergoing investigation for better understanding and
      identification.

PMID- 12044437
TI  - Repair of an anomalous left coronary artery.
AB  - We describe a patient with an anomalous single coronary artery who presented with
      a syndrome of atypical chest pain. Coronary angiography revealed a single right
      coronary ostium, with a narrowed left coronary artery originating at the right
      coronary ostium. The proximal portion of the left coronary artery that was
      narrowed was noted to run in the aortic wall. We describe the operative
      management of this patient using ostial remodeling.

PMID- 12044438
TI  - Spontaneous perforation of a non-aneurysmal visceral aorta.
AB  - A 77 year-old woman with mild osteoarthritis and Sjogren's Syndrome presented to
      an outside hospital with mild abdominal and back pain. The initial computed
      tomography (CT) scan was essentially negative. The repeat CT scan after 1 week of
      medical therapy was suspicious for a contained rupture of the visceral aorta. She
      was emergently transferred to the University of Chicago. Emergent aortography
      confirmed the diagnosis and revealed wide patency of the visceral and renal
      arteries. Upon exploration, there was obvious rupture of the entire right
      posterior aortic wall at the level of the celiac axis with a large right
      retroperitoneal hematoma. Aorto-aortic bypass was performed. The visceral and
      renal vessels were revascularized using separate jump grafts to this 'parallel
      aorta'. The patient tolerated the procedure well and was discharged after 12
      days. Pathologic examination of the aortic wall was essentially negative. She is
      well on follow-up after 20 months. To our knowledge, this is the second reported
      case of spontaneous contained rupture of the visceral aorta.

PMID- 12044439
TI  - Severe hemolysis due to cloth wear 23 years after aortic valve replacement on a
      Starr-Edwards ball valve model 2320.
AB  - Despite iron substitution therapy, a patient developed severe hemolytic anemia 23
      yr after insertion of a cloth-covered Starr-Edwards model 2320 aortic valve
      prosthesis. The prosthesis showed no sign of significant dysfunction. Upon
      removal, it showed extensive cloth wear on the inner surface of all three struts;
      one strut was completely denuded of its cloth covering. Hemolysis immediately
      resolved after replacement with a St Jude aortic prosthesis.

PMID- 12044440
TI  - Triple valve replacement in a patient with severe carcinoid heart disease.
AB  - We report on the case of a 34-year-old male patient suffering from end-stage
      carcinoid heart disease with severe tricuspid, pulmonary and mitral valve
      regurgitation. In addition, a persisting foramen ovale was present. The primary
      carcinoid tumor was never discovered. However, urine 5-hydroxy-indole-acetic-acid
      (5-HIAA) were consistently elevated after the first diagnosis of carcinoid
      disease and after eight years of medication with Octreotide and Interferon alpha
      2b our patient developed significant cardiac insufficiency mainly due to severe
      valvular dysfunction. Ultimately, mechanical tricuspid, mitral and pulmonary
      valve replacement was performed. Twelve hours following the operation the patient
      had to be returned to the operating room for persisting intrathoracic hemorrhage.
      He recovered uneventfully and was discharged from hospital on day 37. Twelve
      months following triple valve replacement the cardiac status recovered from
      preoperative NYHA-IV to NYHA-I.

PMID- 12044441
TI  - Arterial compression of the right common iliac vein; an unusual anatomical
      variant.
AB  - Compression of the left common iliac vein by the right common iliac artery has
      been well described (Cockett's syndrome). The authors describe a case report of
      compression of the right common iliac vein by the right internal iliac artery.
      The patient presented with ipsilateral lower limb oedema. Venography showed
      smooth extrinsic compression of the right common iliac vein. The CT scan was
      initially interpreted as showing no extrinsic mass or obvious compressing lesion
      and lymphography was normal. It was the duplex scan which showed the bifurcation
      of the right common iliac artery crossing the right common iliac vein and causing
      significant extrinsic compression.

PMID- 12044443
TI  - Health implications of creatine: can oral creatine supplementation protect
      against neurological and atherosclerotic disease?
AB  - Major achievements made over the last several years have highlighted the
      important roles of creatine and the creatine kinase reaction in health and
      disease. Inborn errors of metabolism have been identified in the three main steps
      involved in creatine metabolism: arginine:glycine amidinotransferase (AGAT), S
      adenosyl-L-methionine:N-guanidinoacetate methyltransferase (GAMT), and the
      creatine transporter. All these diseases are characterized by a lack of creatine
      and phosphorylcreatine in the brain, and by (severe) mental retardation.
      Similarly, knockout mice lacking the brain cytosolic and mitochondrial isoenzymes
      of creatine kinase displayed a slightly increased creatine concentration, but no
      phosphorylcreatine in the brain. These mice revealed decreased weight gain and
      reduced life expectancy, disturbed fat metabolism, behavioral abnormalities and
      impaired learning capacity. Oral creatine supplementation improved the clinical
      symptoms in both AGAT and GAMT deficiency, but not in creatine transporter
      deficiency. In addition, creatine supplementation displayed neuroprotective
      effects in several animal models of neurological disease, such as Huntington's
      disease, Parkinson's disease, or amyotrophic lateral sclerosis. All these
      findings pinpoint to a close correlation between the functional capacity of the
      creatine kinase/phosphorylcreatine/creatine system and proper brain function.
      They also offer a starting-point for novel means of delaying neurodegenerative
      disease, and/or for strengthening memory function and intellectual
      capabilities.Finally, creatine biosynthesis has been postulated as a major
      effector of homocysteine concentration in the plasma, which has been identified
      as an independent graded risk factor for atherosclerotic disease. By decreasing
      homocysteine production, oral creatine supplementation may, thus, also lower the
      risk for developing, e.g., coronary heart disease or cerebrovascular disease.
      Although compelling, these results require further confirmation in clinical
      studies in humans, together with a thorough evaluation of the safety of oral
      creatine supplementation.

PMID- 12044444
TI  - Somatostatin modulates the behavioral effects of dopamine receptor activation in
      parkinsonian rats.
AB  - Somatostatin may play a role in several neuropsychiatric disorders, including
      Parkinson's disease. Although functional interactions between somatostatinergic
      and dopaminergic transmitter systems have been well documented, no study has been
      conducted in animals with experimental Parkinsonism to explore the effects of
      somatostatin on dopamine receptor-mediated behavior. In the present study, rats
      with unilateral 6-hydroxydopamine-induced destruction of the medial forebrain
      bundle were assessed following administration of the dopamine(1/2) receptor
      agonist apomorphine. Ipsilateral intrastriatal infusion of somatostatin produced
      a dose-related inhibition of apomorphine-induced rotations with maximal effect at
      a dose of 7.5 microg in 2 microl. This inhibitory effect of somatostatin was
      antagonized by the somatostatin antagonist cyclo-somatostatin (0.1 microg in 2
      microl, intrastriatally). Neither somatostatin (up to 15 microg in 2 microl) nor
      cyclo-somatostatin on its own induced rotations; similarly, this dose of cyclo
      somatostatin did not affect apomorphine-induced rotations. From these results we
      suggest that exogenous somatostatin, by directly acting on its specific receptors
      in the striatum, inhibits the effects of dopamine receptor activation in
      parkinsonian rats. We conclude that therapies based on modulation of somatostatin
      may be worth exploring in the management of Parkinson's disease and other
      disorders of the basal ganglia.

PMID- 12044445
TI  - Neuronal and inducible nitric oxide synthase expressions and activities in the
      hippocampi and cortices of young adult, aged cognitively unimpaired, and impaired
      Long-Evans rats.
AB  - Nitric oxide (NO) is a neurosignaling molecule that appears to play a significant
      role in learning and memory. This molecule has also been implicated in
      neurotoxicity due to its oxidative properties. Previous experiments from our
      laboratories have demonstrated elevated hippocampal and cortical neuronal nitric
      oxide synthase (NOS) mRNA levels in aged cognitively unimpaired and impaired Long
      Evans rats, which could represent either increased neuronal NOS activity thereby
      leading to NO-mediated neurotoxicity, or a compensatory response by aged neurones
      to maintain physiological nitric oxide output. The current study measured the
      protein expression and activity levels of neuronal and inducible NOS in young
      adult (6 months) and aged (24-26 months) Long-Evans rats by means of western
      blotting and NOS activity assay. Aged animals were assigned as either cognitively
      unimpaired or aged with moderate cognitive impairments based on their
      performances in the Morris water maze behavioural task. Our results showed that
      hippocampal and cortical neuronal NOS expressions were significantly decreased in
      aged animals. These aged animals also exhibited increased hippocampal and
      cortical inducible NOS expressions. Between the two aged animal groups,
      cognitively impaired rats showed significantly lower hippocampal and cortical
      neuronal but higher hippocampal inducible NOS expressions. Young adult rats
      exhibited significantly higher hippocampal and cortical NOS activities than the
      aged animals. Aged animals with cognitive deficits showed significantly lower
      hippocampal NOS activity than cognitively unimpaired aged rats. Our data indicate
      that aging is associated with a decline in neuronal but elevated inducible NOS
      functioning in brain areas involved in learning and memory. These phenomena could
      contribute to the cognitive deficits observed in a sub-population of aged
      animals.

PMID- 12044446
TI  - BK channel activity determines the extent of cell degeneration after oxygen and
      glucose deprivation: a study in organotypical hippocampal slice cultures.
AB  - BK channels are voltage- and calcium-dependent potassium channels whose
      activation tends to reduce cellular excitability. In hippocampal pyramidal cells,
      BK channels repolarize somatic action potentials, and recent immunogold and
      electrophysiological analyses have revealed a presynaptic pool of BK channels
      that can regulate glutamate release. Agents that modulate BK channel activity
      would therefore be expected to affect cell excitability and neurotransmitter
      release also under pathological conditions. We have investigated the role of BK
      potassium channels in a model of ischemia-induced nerve cell degeneration.
      Organotypical slice cultures of rat hippocampus were exposed to oxygen and
      glucose deprivation (OGD), and cell death was assessed by the fluorescent dye
      propidium iodide. OGD induced cell death in the CA1 region and to a lesser extent
      in CA3. Treatment with the BK channel blockers, paxilline and iberiotoxin, during
      and after OGD induced increased cell death in CA1 and CA3. Both BK channel
      blockers also sensitized the relatively resistant granule cells in fascia dentata
      to OGD. The effect of paxilline and iberiotoxin was evident from 3 h after OGD,
      indicating a role of BK channels early in the post-ischemic phase or during OGD
      itself. The BK channel opener, NS1619, turned out to be gliotoxic, and this
      effect was not counteracted by paxilline and iberiotoxin. Our data show that
      blockade of BK channels aggravates OGD-induced cell damage and suggest that BK
      channels act as a kind of 'emergency brake' during and/or after ischemia.
      Accordingly, the BK channel is a potential molecular target for neuroprotective
      therapy in stroke.

PMID- 12044447
TI  - Up-regulation of cystatin C expression in the murine hippocampus following
      perforant path transections.
AB  - Cystatins are endogenous cysteine protease inhibitors that modulate the turnover
      of intracellular and extracellular proteins. These inhibitors are strongly
      implicated in a variety of pathological processes such as tumor metastasis and
      many degenerating CNS disorders. Here we report the expression of cystatin C, a
      major cysteine protease inhibitor of mammalian animals, in the murine hippocampus
      at 3, 7, 15 and 30 days following perforant path transections. Northern blot
      analysis showed that cystatin C transcripts were up-regulated in a transient
      manner with a significant increase at 7 and 15 days post-lesion (219% and 185% of
      control, respectively) in the rat hippocampus after entorhinal deafferentation.
      In situ hybridization and immunohistochemistry confirmed the time-dependent up
      regulation of both cystatin C mRNA and protein expressions in a mouse model which
      initiated at 3 days post-lesion, reached maximal levels 7-15 days post-lesion,
      and remained slightly elevated by day 30 post-lesion. The modulation of cystatin
      C expression was observed to occur specifically in the entorhinally denervated
      zones: the stratum lacunosum-moleculare of the hippocampus and the outer
      molecular layer of the dentate gyrus. Double labeling by either a combination of
      in situ hybridization for cystatin C with immunohistochemistry for glial
      fibrillary acidic protein or double immunofluorescence staining for both proteins
      in mouse hippocampus at 7 and 15 days post-lesion revealed that most cystatin C
      expressing cells are astrocytes. From these results we suggest that the
      spatiotemporal up-regulation of cystatin C in the hippocampus is induced by
      entorhinal deafferentation and that cystatin C may be involved in the astroglia
      mediated neural plasticity events in the hippocampus following perforant path
      transections.

PMID- 12044448
TI  - Depolarizing glycine responses in Cajal-Retzius cells of neonatal rat cerebral
      cortex.
AB  - We investigated the properties of glycine-induced responses in Cajal-Retzius
      cells, a neuronal cell type essential for the establishment of neocortical
      lamination. Whole-cell and gramicidin-perforated patch-clamp recordings were
      performed on visually identified Cajal-Retzius cells in tangential slices from
      neonatal rat cortex (postnatal days 0-3). With a pipette Cl(-) concentration of
      50 mM, bath application of 1 mM glycine induced a membrane depolarization of
      32.8+/-7.4 mV and a massive decrease in membrane resistance by 88+/-1.4%. The
      membrane depolarization was abolished in the presence of the glycinergic
      antagonists strychnine (30 microM) and phenylbenzene-omega-phosphono-alpha-amino
      acid (100 microM), while the GABA(A) receptor antagonist bicuculline (100 microM)
      and the glutamatergic antagonist (+/-)-2-amino-5-phosphonopentatonic acid (60
      microM) were without effect, suggesting that the glycine-induced membrane
      responses were mediated exclusively by the strychnine-sensitive glycine receptor.
      The EC(50) for activation of glycine receptors was 0.54 mM, 1.62 mM and 2.41 mM,
      for the glycinergic agonists glycine, beta-alanine and taurine, respectively.
      Since the reversal potential of the glycine-induced currents showed a strong
      dependency on the intracellular chloride concentration and was virtually
      unaffected under HCO(3)(-)-free conditions, the activation of glycine receptors
      was probably linked to Cl(-) fluxes with little contribution of HCO(3)(-) ions.
      Perforated patch recordings from Cajal-Retzius cells demonstrated that glycine
      elicited depolarizing responses mediated by Cl(-) currents which reversed at 
      41+/-3.7 mV. In summary, from these results we suggest that Cajal-Retzius cells
      of the neonatal rat cerebral cortex express functional strychnine-sensitive
      glycine receptors that mediate depolarizing membrane responses via Cl(-) efflux.

PMID- 12044449
TI  - Immobilization stress rapidly modulates BDNF mRNA expression in the hypothalamus
      of adult male rats.
AB  - We demonstrated that short times (15 min) of immobilization stress application
      induced a very rapid increase in brain-derived neurotrophic factor (BDNF) mRNA
      expression in rat hypothalamus followed by a BDNF protein increase. The early
      change in total BDNF mRNA level seems to reflect increased expression of the BDNF
      transcript containing exon III, which was also rapidly (15 min) modified. The
      paraventricular and supraoptic nuclei, two hypothalamic nuclei closely related to
      the stress response and known to express BDNF mRNA, were analyzed by in situ
      hybridization following immobilization stress. In the parvocellular region of the
      paraventricular nucleus, BDNF mRNA levels increased very quickly as early as 15
      min. In contrast, in the two other regions examined, the lateral and ventral
      magnocellular regions of the paraventricular nucleus, as well as in the
      supraoptic nucleus, signals above control were increased later, at 60 min. After
      stress application, plasma adrenocorticotropic hormone and corticosterone levels
      were strongly and significantly increased at 15 min. These studies demonstrated
      that immobilization stress challenge very rapidly enhanced BDNF mRNA levels as
      well as the protein, suggesting that BDNF may play a role in plasticity processes
      related to the stress response.

PMID- 12044450
TI  - Adenosine A(2A) receptor facilitation of hippocampal synaptic transmission is
      dependent on tonic A(1) receptor inhibition.
AB  - Adenosine tonically inhibits synaptic transmission through actions at A(1)
      receptors. It also facilitates synaptic transmission, but it is unclear if this
      facilitation results from pre- and/or postsynaptic A(2A) receptor activation or
      from indirect control of inhibitory GABAergic transmission. The A(2A) receptor
      agonist, CGS 21680 (10 nM), facilitated synaptic transmission in the CA1 area of
      rat hippocampal slices (by 14%), independent of whether or not GABAergic
      transmission was blocked by the GABA(A) and GABA(B) receptor antagonists,
      picrotoxin (50 microM) and CGP 55845 (1 microM), respectively. CGS 21680 (10 nM)
      also inhibited paired-pulse facilitation by 12%, an effect prevented by the A(2A)
      receptor antagonist, ZM 241385 (20 nM). These effects of CGS 21680 (10 nM) were
      occluded by adenosine deaminase (2 U/ml) and were made to reappear upon direct
      activation of A(1) receptors with N(6)-cyclopentyladenosine (CPA, 6 nM). CGS
      21680 (10 nM) only facilitated (by 17%) the K(+)-evoked release of glutamate from
      superfused hippocampal synaptosomes in the presence of 100 nM CPA. This effect of
      CGS 21680 (10 nM), in contrast to the isoproterenol (30 microM) facilitation of
      glutamate release, was prevented by the protein kinase C inhibitors,
      chelerythrine (6 microM) and bisindolylmaleimide (1 microM), but not by the
      protein kinase A inhibitor, H-89 (1 microM). Isoproterenol (30 microM), but not
      CGS 21680 (10-300 nM), enhanced synaptosomal cAMP levels, indicating that the CGS
      21680-induced facilitation of glutamate release involves a cAMP-independent
      protein kinase C activation. To discard any direct effect of CGS 21680 on
      adenosine A(1) receptor, we also show that in autoradiography experiments CGS
      21680 only displaced the adenosine A(1) receptor antagonist, 1,3-dipropyl-8
      cyclopentyladenosine ([(3)H]DPCPX, 0.5 nM) with an EC(50) of 1 microM in all
      brain areas studied and CGS 21680 (30 nM) failed to change the ability of CPA to
      displace DPCPX (1 nM) binding to CHO cells stably transfected with A(1)
      receptors. Our results suggest that A(2A) receptor agonists facilitate
      hippocampal synaptic transmission by attenuating the tonic effect of inhibitory
      presynaptic A(1) receptors located in glutamatergic nerve terminals. This might
      be a fine-tuning role for adenosine A(2A) receptors to allow frequency-dependent
      plasticity phenomena without compromising the A(1) receptor-mediated
      neuroprotective role of adenosine.

PMID- 12044451
TI  - Involvement of nitric oxide, cyclic GMP and phosphodiesterase 5 in excitatory
      amino acid and GABA release in the nucleus accumbens evoked by activation of the
      hippocampal fimbria.
AB  - It is known that the nucleus accumbens contains all elements of the nitric oxide
      (NO)-cyclic GMP (cGMP) system but the role of NO in this nucleus is not well
      understood. We investigated the contribution of the NO-cGMP system in the
      neurotransmission elicited by hippocampal nerve signals which are propagated to
      the nucleus accumbens via the fornix/fimbria. This glutamatergic hippocampus
      accumbens projection was electrically stimulated for short periods in the
      urethane-anaesthetized rat. The nucleus accumbens was simultaneously superfused
      by the push-pull technique with compounds that influence the NO system and the
      released glutamate, aspartate and GABA were determined in the superfusate.
      Superfusion of the nucleus accumbens with the NO donor, PAPA/NO, enhanced basal
      release of the investigated amino acids with a complex concentration dependency.
      The release of glutamate and aspartate was also increased by the inhibitor of
      phosphodiesterase 5, UK-114,542. The PAPA/NO-elicited release of glutamate and
      aspartate was diminished by superfusion with the inhibitor of guanylyl cyclase,
      NS 2028. Basal release of amino acid transmitters was not influenced by NS 2028
      and the NO synthase inhibitor, 7-NINA.Electrical stimulation of the
      fornix/fimbria increased the outflow of aspartate, glutamate and GABA in the
      nucleus accumbens. The stimulation-evoked release was abolished by superfusion of
      the nucleus with tetrodotoxin and strongly diminished by NS 2028, 7-NINA and N(G)
      nitro-L-arginine methyl ester (L-name), while PAPA/NO facilitated stimulation
      evoked release of these neurotransmitters. UK-114,542 also enhanced the evoked
      release of glutamate and aspartate while evoked GABA release was not influenced
      by the phosphodiesterase inhibitor. These findings indicate that NO plays the
      role of an excitatory transmitter in the nucleus accumbens and that nerve signals
      from the hippocampus propagated via fornix/fimbria induce NO synthesis in the
      nucleus accumbens. NO does not exert a tonic influence on basal release but
      facilitates release of aspartate, glutamate and GABA through increased cGMP
      synthesis. Phosphodiesterase 5 seems to be involved in the termination of the NO
      effect in glutamatergic but not in GABAergic neurons.

PMID- 12044452
TI  - Regulation of mu-opioid receptors, G-protein-coupled receptor kinases and beta
      arrestin 2 in the rat brain after chronic opioid receptor antagonism.
AB  - The aim of this study was to analyse the biochemical and behavioural consequences
      of chronic treatment with opioid receptor antagonists in rats. We have evaluated
      the respiratory depressant and antinociceptive effects of the mu-opioid agonist
      sufentanil, the density of brain mu-opioid receptors, and the expression of G
      protein-coupled receptor kinases and beta-arrestin 2 in cerebral cortex and
      striatum, following sustained opioid receptor blockade. Our results demonstrate
      that 24 h after interruption of 7 days chronic infusion of naltrexone (120
      microg/h), the respiratory depressant potency of the mu-opioid receptor agonist
      sufentanil was increased to a similar extent as the antinociceptive potency
      (about three-fold). This was accompanied by mu-opioid receptor up-regulation in
      several areas of the rat brain associated with opioid control of pain perception
      and breathing. Moreover, chronic treatment with either naltrexone (120 microg/h)
      or naloxone (120 microg/h) caused significant increases in the expression levels
      of G-protein-coupled receptor kinases types 2, 3, and 6, and of beta-arrestin 2
      in brain cortex and striatum. Together our data suggest an increased constitutive
      receptor activity secondary to mu-opioid receptor up-regulation following chronic
      antagonist treatment.

PMID- 12044453
TI  - Cataplexy-related neurons in the amygdala of the narcoleptic dog.
AB  - The amygdala plays an important role in the interpretation of emotionally
      significant stimuli and has strong projections to brainstem regions regulating
      muscle tone and sleep. Cataplexy, a symptom of narcolepsy, is a loss of muscle
      tone usually triggered by sudden, strong emotions. Extracellular single-unit
      recordings were carried out in the amygdala of narcoleptic dogs to test the
      hypothesis that abnormal activity of a subpopulation of amygdala neurons is
      linked to cataplexy. Of the 218 cells recorded, 31 were sleep active, 78 were
      active in both waking and rapid-eye-movement sleep, 88 were maximally active
      during waking, and 21 were state independent. Two populations of cells showed a
      significant change in activity with cataplexy. A population of sleep active cells
      localized to central and basal nucleus increased discharges prior to and during
      cataplexy. A population of wake active cells localized to the cortical nucleus
      decreased activity prior to and during cataplexy. We hypothesize that these cell
      populations have a role in mediation or modulation of cataplexy through
      interactions with meso-pontine regions controlling atonia. The anticholinesterase
      physostigmine, at doses which increased cataplexy, did not alter the activity of
      the cataplexy-related cells or of other amygdala cells, suggesting that its
      effect on cataplexy is mediated 'downstream' of the amygdala. The alpha-1 blocker
      prazosin, at doses which increased cataplexy, increased discharge in a subgroup
      of the cataplexy active cells and in a number of other amygdala cells, indicating
      that prazosin may modulate cataplexy by its action on amygdala cells or their
      afferents.

PMID- 12044454
TI  - The auditory evoked magnetic fields to very high frequency tones.
AB  - We studied the auditory evoked magnetic fields (AEFs) in response to pure tones
      especially at very high frequencies (from 4000 Hz to 40,000 Hz). This is the
      first systematic study of AEFs using tones above 5000 Hz, the upper audible range
      of humans, and ultrasound. We performed two experiments. In the first, AEFs were
      recorded in 12 subjects from both hemispheres under binaural listening
      conditions. Six types of auditory stimulus (pure tones of five different
      frequencies: 4000 Hz, 8000 Hz, 10,000 Hz, 12,000 Hz, 14,000 Hz, and a click sound
      as the target stimulus) were used. In the second experiment, we used 1000 Hz,
      15,000 Hz, and two ultrasounds with frequencies of 20,000 Hz and 40,000 Hz. The
      subjects could detect all stimuli in the first experiment but not the ultrasounds
      in the second experiment. We analyzed N1m, the main response with approximately
      100 ms in peak latency, and made the following findings. (1) N1m responses to the
      tones up to 12,000 Hz were clearly recorded from at least one hemisphere in all
      12 subjects. N1m for 14,000 Hz was identified in at least one hemisphere in 10
      subjects, and in both hemispheres in six subjects. No significant response could
      be identified to ultrasounds over 20,000 Hz. (2) The amplitude of the N1m to the
      tones above 8000 Hz was significantly smaller than that to 4000 Hz in both
      hemispheres. There was a tendency for the peak latency of the N1m to be longer
      for the tones with higher frequencies, but no significant change was found. (3)
      The equivalent current dipole (ECD) of the N1m was located in the auditory
      cortex. There was a tendency for the ECD for the tones with higher frequencies to
      lie in more medial and posterior areas, but no significant change was found. (4)
      As for the interhemispheric difference, the N1m amplitude for all frequency tones
      was significantly larger and the ECDs were estimated to be located more anterior
      and medial in the right hemisphere than the left. The priority of the right
      hemisphere, that is the larger amplitude, for very high frequency tones was
      confirmed. (5) The orientation of the ECD in the left hemisphere became
      significantly more vertical the higher the tones. This result was consistent with
      previous studies which revealed the sensitivity of the frequency difference in
      the left hemisphere. From these findings we suggest that tonotopy in the auditory
      cortex exists up to the upper limit of audible range within the small area, where
      the directly air-conducted ultrasounds are not reflected.

PMID- 12044455
TI  - A single lipopolysaccharide administration is sufficient to induce a long-term
      desensitization of the hypothalamic-pituitary-adrenal axis.
AB  - We have previously shown that a single exposure of adult rats to a severe
      emotional stressor such as immobilization is able to exert a long-term
      desensitization of the response of the hypothalamic-pituitary-adrenal (HPA) axis
      to the same stimulus when applied days to weeks later. Surprisingly, the
      intensity of the effect increased with time elapsed between the two exposures,
      suggesting that we are dealing with a new type of stress-associated phenomenon.
      Taking into account the clinical importance of tolerance to endotoxin, in the
      present study we assessed whether a single exposure to an immunological stressor
      such as lipopolysaccharide can induce effects similar to those of immobilization.
      Rats injected with lipopolysaccharide (1 mg/kg) showed a reduction of the
      response of the corticotropin-releasing factor mRNA in the paraventricular
      nucleus of the hypothalamus after a new lipopolysaccharide injection 4, but not 2
      weeks later. In an additional experiment using a different blood sampling
      procedure, adrenocorticotropin hormone, corticosterone and tumor necrosis factor
      alpha responses were reduced approximately to the same extent by previous
      experience with lipopolysaccharide either 1 or 4 weeks before. Our data suggest
      that a previous single exposure to lipopolysaccharide induces a long-lasting
      tolerance of the HPA axis that likely involves some kind of learning-like brain
      plasticity.

PMID- 12044456
TI  - Maturational and maintenance effects of testosterone on terminal axon density and
      neuropeptide expression in the rat vas deferens.
AB  - Testosterone causes growth of many pelvic ganglion cells at puberty and their
      maintenance during adulthood. Here we have focused on two populations of pelvic
      ganglion cells that project to the rat vas deferens: noradrenergic neurons that
      innervate the smooth muscle and synthesize neuropeptide Y, and cholinergic
      neurons that primarily innervate the mucosa and contain vasoactive intestinal
      peptide. We have assessed the muscle innervation after pre- or postpubertal
      castration, using immunohistochemistry to determine axon density and
      radioimmunoassay to quantify levels of neuropeptides in tissue extracts. Our
      results show that androgen deprivation in each period causes substantial effects.
      Noradrenergic axons in the muscle increase in density after castration, partly
      due to organ size being smaller than age-matched controls. However, when
      corrected for target size, there is an overall decrease in total number of axons.
      This implies that androgen exposure at puberty has a direct effect on neurons to
      ensure that the adult pattern of innervation is attained, and that this is not
      simply by matching terminal field to target size. Similar effects of pre- and
      postpubertal castration imply that continued exposure to testosterone is
      necessary to maintain normal target innervation. Castration in both time periods
      increased the density of axons containing vasoactive intestinal peptide, however
      the effects of castration on the total number of these axons in the muscle were
      more variable. The concentration of vasoactive intestinal peptide increased
      substantially following either pre- or postpubertal castration although absolute
      amounts per vas deferens were decreased. Effects on neuropeptide Y concentration
      were less pronounced but the total amount per vas deferens was decreased after
      pre- or postpubertal castration. Our study shows that the action of testosterone
      (or a metabolite) on a pelvic ganglion cell soma is likely to reflect a change in
      its terminal field, but that these effects are not mediated simply by
      testosterone influencing the size of its target organ.

PMID- 12044457
TI  - Involvement of 5-hydroxytryptamine(1A) receptors in the descending anti
      nociceptive pathway from periaqueductal gray to the spinal dorsal horn in intact
      rats, rats with nerve injury and rats with inflammation.
AB  - Studies have shown that 5-hydroxytryptamine (5-HT) plays an important role in the
      descending pathway of pain modulation from brainstem to the spinal cord. Using
      selective 5-HT receptor antagonists, the present study investigated which type of
      5-HT receptor(s) in the spinal cord was involved in the morphine-induced anti
      nociception in intact rats, in rats with nerve injury and in rats with
      inflammation. The hindpaw withdrawal latencies decreased significantly after
      sciatic nerve injury and hindpaw inflammation compared with intact rats.
      Intrathecal administration of 25 or 10 microg of the selective 5-HT(1A) recepter
      antagonist spiroxatrine, but not 1 microg of spiroxatrine, significantly blocked
      the increased hindpaw withdrawal latencies to thermal and mechanical stimulation
      induced by intra-periaqueductal gray injection of 1 microg of morphine in intact
      rats. Intrathecal injection of the 5-HT(2) receptor antagonist RS 102221 and the
      5-HT(3) receptor antagonist MDL 72222 had no significant effects on the increased
      hindpaw withdrawal latencies to both noxious stimulations induced by intra
      periaqueductal gray injection of morphine. Furthermore, intrathecal
      administration of spiroxatrine, but not RS 102221 nor MDL 72222, significantly
      attenuated the increased hindpaw withdrawal latencies induced by intra
      periaqueductal gray administration of morphine in rats with nerve injury and in
      rats with inflammation. The results demonstrate that the 5-HT(1A) receptor, not 5
      HT(2) nor 5-HT(3) receptor, plays an important role in the descending pathway of
      anti-nociception from the brainstem to the spinal cord in intact rats, in rats
      with nerve injury and in rats with inflammation.

PMID- 12044458
TI  - Interleukin-2 gene therapy of chronic neuropathic pain.
AB  - Previous research has revealed an antinociceptive (analgesic) effect of
      interleukin-2 (IL-2) in central and peripheral nervous systems. Unfortunately IL
      2 is very short-lived in vivo, so it is impractical to apply IL-2 for analgesia
      in clinic. This study was performed to evaluate the effect of intrathecal
      delivery of human IL-2 gene on rat chronic neuropathic pain induced by chronic
      constriction injury of the sciatic nerve. Human IL-2 cDNA was cloned into pcDNA3
      containing a cytomegalovirus promoter. The paw-withdrawal latency induced by
      radiant heat was used to measure the pain threshold. The results showed that
      recombinant human IL-2 had a dose-dependent antinociceptive effect, but that this
      only lasted for 10-25 min. The pcDNA3-IL-2 or pcDNA3-IL-2/lipofectamine complex
      in contrast also showed dose-dependent antinociceptive effects, but these reached
      a peak at day 2-3 and were maintained for up to 6 days. Liposome-mediated pcDNA3
      IL-2 produced a more powerful antinociceptive effect than pcDNA3-IL-2 alone. The
      paw-withdrawal latencies were not affected by control treatments such as vehicle,
      lipofectamine, pcDNA3, or pcDNA3-lipofectamine. In the experimental groups, human
      IL-2 mRNA was detected by reverse transcription-polymerase chain reaction in the
      lumbar spinal pia mater, dorsal root ganglion, sciatic nerve, and spinal dorsal
      horn, but not in gastrocnemius muscle. The expressed IL-2 profile detected by
      western blot coincided with its mRNA profile except it was present in the spinal
      dorsal horn at a higher level. Furthermore, human IL-2 assayed by enzyme-linked
      immunosorbent assay in cerebrospinal fluid could still be detected at day 6, but
      lower than day 3. The antinociceptive effect of pcDNA3-IL-2 could be blocked by
      naloxone, showing some relationship of the antinociceptive effect produced by IL
      2 gene to the opioid receptors. It is hoped that the new delivery approach of a
      single intrathecal injection of the IL-2 gene described here may be of some
      practical use as a part of a gene therapy for treating neuropathic pain.

PMID- 12044459
TI  - The effect of excitotoxic lesions of the pedunculopontine tegmental nucleus on
      performance of a progressive ratio schedule of reinforcement.
AB  - The pedunculopontine tegmental nucleus has connections with sites in both dorsal
      and ventral striatum, and a number of studies have suggested that it has a role
      in reward-related behaviour. The present experiment aimed to investigate the
      perception of reward in pedunculopontine tegmental nucleus-lesioned rats
      responding for food under a progressive ratio schedule, which measures
      willingness to work for a given reward. Rats were trained on a progressive ratio
      5 schedule for food reward, then given ibotenic acid or sham lesions of the
      pedunculopontine tegmental nucleus. Their performance under this schedule was
      examined again following recovery from surgery. Compared with sham-lesioned rats,
      those with lesions of the pedunculopontine tegmental nucleus showed significantly
      reduced breaking points and significantly longer post-reinforcement pauses.
      However, there was no difference between the groups in their latency to collect
      food pellets once earned, suggesting that pedunculopontine tegmental nucleus
      excitotoxin and sham-lesioned rats were equally motivated by the presence of
      food. Excitotoxin-lesioned rats made significantly more responses on the control
      lever and more entries to the food hopper as progressive ratio increment
      increased, but did not differ from controls when the schedule requirement was
      low. These results are interpreted as indicating no global loss of motivation,
      since lesioned rats performed normally at low schedule requirements, and were as
      fast as controls to collect pellets. But as the schedule requirement increased,
      excitotoxin-lesioned rats showed reductions in responding on the active lever
      (that is, a reduction in breaking point) and an increase in inappropriate
      responses towards the food hopper and the control lever.We consider these data to
      indicate that the behavioural deficits in pedunculopontine-lesioned rats arise
      not from a sensory or hedonic change, but from alteration in the control of motor
      output.

PMID- 12044460
TI  - Muscarinic, adenosine A(2) and histamine H(3) receptor modulation of haloperidol
      induced c-fos expression in the striatum and nucleus accumbens.
AB  - It is generally believed that haloperidol exerts its motor side effects and
      therapeutic effects mainly by antagonizing dopamine D(2) receptors in the
      striatum and the nucleus accumbens, respectively. Several
      neurotransmitters/modulators, including glutamate, acetylcholine, adenosine and
      histamine, affect dopaminergic activity in these centers. We have recently shown
      that N-methyl-D-aspartate receptor-mediated modulation of haloperidol-induced c
      fos expression differs in functionally specific regions of the striatum and the
      nucleus accumbens. In the present study, the entire striatum and the nucleus
      accumbens were comprehensively examined for the pattern of modulation of
      haloperidol-induced c-fos expression by adenosine A(2), histamine H(3) and
      muscarinic receptor antagonists. Blockade of muscarinic and H(3) receptors
      resulted in a profound suppression of haloperidol-induced c-fos expression in the
      dorsolateral part of the striatum. In addition, the H(3) receptor antagonist
      suppressed the effects of haloperidol in the ventrolateral aspect of the striatum
      and the rostral parts of the medial striatum. Muscarinic receptor antagonists
      suppressed haloperidol-induced c-fos expression throughout the shell and in the
      mid-level of the core of the nucleus accumbens while A(2) and H(3) receptor
      antagonists did not.We found that the muscarinic and H(3) receptor antagonists
      suppress the induction of c-fos by haloperidol in the dorsolateral aspect of the
      striatum, an area implicated in the development of extrapyramidal motor symptoms
      following chronic haloperidol treatment. By contrast, haloperidol-induced c-fos
      expression in the nucleus accumbens, an area implicated in the therapeutic
      effects of haloperidol, was suppressed by the muscarinic receptor antagonist, but
      not by the H(3) receptor antagonist. Therefore we conclude that H(3) receptor
      modulation may provide a useful therapeutic target in future efforts to minimize
      neuroleptic-induced motor side effects.

PMID- 12044461
TI  - Activation and up-regulation of spinal cord nitric oxide receptor, soluble
      guanylate cyclase, after formalin injection into the rat hind paw.
AB  - Nitric oxide synthase is expressed abundantly in the spinal cord, and nitric
      oxide (NO) has been shown to play important roles in the central mechanism of
      inflammatory hyperalgesia. However, the expression and function of the NO
      receptor, soluble guanylate cyclase, is not fully understood in this processing
      at the spinal cord level. In the present study, we report that the soluble
      guanylate cyclase alpha(1) subunit but not the beta(1) subunit was expressed in
      rat spinal cord, particularly in the dorsal horn. We showed that intrathecal
      administration of a selective inhibitor of soluble guanylate cyclase, 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, produced a significant anti-nociception
      demonstrated by the decrease in the number of flinches and shakes in the formalin
      induced inflammatory pain model. This was accompanied by a marked reduction in
      formalin-induced c-fos expression in the spinal cord. During formalin-induced
      long-lasting inflammation, we found that the expression of the alpha(1) subunit
      of soluble guanylate cyclase was dramatically increased in the lumbar spinal cord
      on the second and fourth days after formalin injection into the dorsal side of a
      hind paw. Intraperitoneal pretreatment with an N-methyl-D-aspartate (NMDA)
      receptor antagonist, dizocilpine maleate (MK-801), and a neuronal NO synthase
      inhibitor, 7-nitroindazole, not only significantly blocked formalin-induced
      secondary thermal hyperalgesia but also suppressed formalin-produced increase in
      the alpha(1) subunit of soluble guanylate cyclase in the spinal cord. The present
      results indicate that peripheral inflammation not only initially activates but
      also later up-regulates soluble guanylate cyclase expression via the NMDA
      receptor-NO signaling pathway, suggesting that soluble guanylate cyclase might be
      involved in the central mechanism of formalin-induced inflammatory hyperalgesia
      in the spinal cord.

PMID- 12044462
TI  - Sensorimotor functions in transgenic mice expressing the neurofilament/heavy-LacZ
      fusion protein on two genetic backgrounds.
AB  - NFH-LacZ transgenic mice are characterized by expression of a non-endogenous
      fusion protein between a truncated form of mouse NFH (neurofilament of heavy
      molecular weight) and the complete Escherichia coli beta-galactosidase protein.
      These transgenic mice were compared to their respective controls on two
      background strains (C3H and FVB) in several sensorimotor tests. NFH-LacZ mice
      were deficient in tests requiring balance and equilibrium in a manner generally
      independent of genetic background. In particular, NFH-LacZ mice fell more quickly
      than controls from two stationary beams and had fewer rears in an open-field. The
      transgenic mice were also impaired during the initial trials of sensorimotor
      learning on the rotorod. We conclude that despite the absence of overt signs of
      sensorimotor weakness in their home cage, the disruption of the NFH gene, causing
      neurofilament accumulations in the cell body and diminished axonal calibers of
      motoneurons, is sufficient to cause motor deficits that resemble the early stages
      of amyotrophic lateral sclerosis.

PMID- 12044463
TI  - Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin
      receptor knock-out mice.
AB  - Somatostatin is implicated in a number of physiological functions in the CNS.
      These effects are elicited through the activation of at least five receptor
      subtypes. Among them, sst2 receptors appear the most widely expressed in the
      cortex and hippocampal region. However, the specific role of this somatostatin
      receptor subtype in these regions is largely undetermined. In this study, we
      investigated the role of the sst2 receptor in the hippocampus using mice
      invalidated for the sst2 gene (sst2 KO mice). Complementary experimental
      approaches were used. First, mice were tested in behavioral tests to explore the
      consequences of the gene deletion on learning and memory. Spatial discrimination
      learning in the radial maze was facilitated in sst2 KO mice, while operant
      learning of a bar-pressing task was slightly altered. Mice were then processed
      for electrophysiological study using the ex vivo hippocampal slice preparation.
      Extracellular recordings in the CA1 area showed an enhancement in glutamatergic
      (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the
      magnitude of the short-term potentiation and long-term depression. In contrast,
      long-term potentiation was not significantly altered. Taken together, these data
      demonstrate that somatostatin, acting via sst2 hippocampal receptors, may
      contribute to a global decrease in glutamate efficiency and consequently alter
      glutamate-dependent plasticity and spatial learning.

PMID- 12044464
TI  - In vivo manganese-enhanced magnetic resonance imaging reveals connections and
      functional properties of the songbird vocal control system.
AB  - Injection of manganese (Mn(2+)), a paramagnetic tract tracing agent and calcium
      analogue, into the high vocal center of starlings labeled within a few hours the
      nucleus robustus archistriatalis and area X as observed by in vivo magnetic
      resonance imaging. Structures highlighted by Mn(2+) accumulation assumed the
      expected tri-dimensional shape of the nucleus robustus archistriatalis and area X
      as identified by classical histological or neurochemical methods. The volume of
      these nuclei could be accurately calculated by segmentation of the areas
      highlighted by Mn(2+). Besides confirming previously established volumetric sex
      differences, Mn(2+) uptake into these nuclei revealed new functional sex
      differences affecting Mn(2+) transport. A faster transport was observed in males
      than in females and different relative amounts of Mn(2+) were transported to
      nucleus robustus archistriatalis and area X in males as compared to females. This
      new in vivo approach, allowing repeated measures, opens new vistas to study the
      remarkable seasonal plasticity in size and activity of song-control nuclei and
      correlate neuronal activity with behavior. It also provides new insights on in
      vivo axonal transport and neuronal activity in song-control nuclei of oscines.

PMID- 12044465
TI  - Galanin modulates the activity of proopiomelanocortin neurons in the isolated
      mediobasal hypothalamus of the male rat.
AB  - It has become apparent that galanin as well as proopiomelanocortin-derived
      peptides, such as beta-endorphin, play an important role in the hypothalamic
      circuitry that regulates neuroendocrine functions and appetite behavior. We have
      recently shown that GalR1 and GalR2 galanin receptor mRNAs are expressed in
      proopiomelanocortin neurons of the arcuate nucleus, suggesting a direct
      modulatory action of galanin on the proopiomelanocortin neuronal system. In the
      present study, we investigated the effect of galanin on beta-endorphin release
      and proopiomelanocortin mRNA expression from male rat mediobasal hypothalamic
      fragments incubated ex vivo. Galanin induced a decrease of spontaneous beta
      endorphin release within the first 30-60 min of incubation and this effect was
      blocked by the galanin receptor antagonist galantide. Co-incubation of galanin
      with FK-506 (tacrolimus), a calcineurin inhibitor, suppressed the inhibitory
      effect of galanin on beta-endorphin release, suggesting that calcineurin is
      involved in the galanin-evoked decrease in beta-endorphin release. Measurement of
      beta-endorphin levels in the tissues at the end of the incubation period (120
      min) revealed that galanin caused a two-fold increase of beta-endorphin peptide
      concentration in the mediobasal hypothalamic tissues. Concurrently, galanin
      induced an increase in the mean density of silver grains overlying
      proopiomelanocortin neurons after 60 min of incubation, an effect antagonized by
      galantide. Finally, reverse transcription-polymerase chain reaction analysis
      revealed that the mRNAs for the three galanin receptor subtypes (i.e. GalR1,
      GalR2, and GalR3) were expressed in the incubated mediobasal hypothalamic
      fragments. Taken as a whole, our results indicate that galanin plays a modulatory
      role on proopiomelanocortin neurons and this interrelation contributes to the
      elucidation of the neural circuitry that controls, among others, gonadotropin
      releasing hormone function.

PMID- 12044466
TI  - Non-classical nuclear localization signal peptides for high efficiency
      lipofection of primary neurons and neuronal cell lines.
AB  - Gene transfer into CNS is critical for potential therapeutic applications as well
      as for the study of the genetic basis of neural development and nerve function.
      Unfortunately, lipid-based gene transfer to CNS cells is extremely inefficient
      since the nucleus of these post-mitotic cells presents a significant barrier to
      transfection. We report the development of a simple and highly efficient
      lipofection method for primary embryonic rat hippocampal neurons (up to 25%
      transfection) that exploits the M9 sequence of the non-classical nuclear
      localization signal of heterogeneous nuclear ribonucleoprotein A1 for targeting
      beta(2)-karyopherin (transportin-1). M9-assistant lipofection resulted in 20-100
      fold enhancement of transfection over lipofection alone for embryonic-derived
      retinal ganglion cells, rat pheochromocytoma (PC12) cells, embryonic rat ventral
      mesencephalon neurons, as well as the clinically relevant human NT2 cells or
      retinoic acid-differentiated NT2 neurons. This technique can facilitate the
      implementation of promoter construct experiments in post-mitotic cells, stable
      transformant generation, and dominant-negative mutant expression techniques in
      CNS cells.

PMID- 12044467
TI  - Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine
      prion disease.
AB  - Peripheral infections in mammals are characterised by local, systemic and CNS
      effects. The latter give rise to sickness behaviour. Pro-inflammatory cytokines
      such as interleukin-1beta (IL-1beta) are thought to be important mediators of
      this neuro-immune signalling (Cartmell et al., 1999). There is anecdotal evidence
      suggesting that peripheral infections in patients with Alzheimer's disease have
      more severe behavioural consequences than those in otherwise healthy elderly
      subjects, and it is well known that brain microglia are activated in the elderly
      and in Alzheimer's disease (McGeer et al., 1987). Using ME7-induced murine prion
      disease as a model of chronic neurodegeneration that displays chronic microglial
      activation, and the intra-peritoneal injection of bacterial lipopolysaccharide to
      mimic a peripheral infection, we have shown that the temperature and activity
      responses of animals with pre-clinical prion disease were exaggerated compared
      with controls, and that this was associated with a significant increase in brain
      levels of IL-1beta. We hypothesise that prior priming of microglia by the
      degenerative process, followed by further activation through signalling from the
      periphery, resulted in increased brain IL-1beta synthesis and the consequent
      acute sickness behavioural responses. These findings demonstrate an interaction
      between peripheral infection and pre-existing CNS inflammation and suggest that
      further stimulation of an already primed microglial population by a peripheral
      infection may drive disease progression in chronic inflammatory conditions such
      as Alzheimer's disease and prion disease.

PMID- 12044468
TI  - Modulatory effects of norepinephrine in the lateral bed nucleus of the stria
      terminalis on behavioral and neuroendocrine responses to acute stress.
AB  - The brain noradrenergic system is activated by stress, and modulates the activity
      of forebrain regions involved in behavioral and neuroendocrine responses to
      stress, such as the lateral bed nucleus of the stria terminalis (BSTL). This
      region of the limbic forebrain receives dense noradrenergic innervation, and has
      been implicated in both anxiety and regulation of the hypothalamic-pituitary
      adrenal axis. We hypothesized that stress-induced release of norepinephrine in
      the BSTL modulates anxiety-like behavioral responses to stress and activation of
      the hypothalamic-pituitary-adrenal stress axis. Using microdialysis, we showed
      that release of norepinephrine was increased in the BSTL of male Sprague-Dawley
      rats during immobilization stress. In the next experiment, we then microinjected
      noradrenergic antagonists into the BSTL immediately prior to acute immobilization
      stress to examine noradrenergic modulation of behavioral stress reactivity.
      Either the alpha(1)-receptor antagonist benoxathian, or a cocktail of beta(1)-
      and beta(2)-receptor antagonists (betaxolol+ICI 118,551) blocked the anxiety-like
      reduction in open-arm exploration on the elevated plus-maze, but not the
      reduction in social behavior induced in the social interaction test. In a third
      experiment, benoxathian reduced plasma levels of adrenocorticotropic hormone
      following stress, but beta-receptor antagonists had no effect. From these results
      we suggest that stress-induced norepinephrine release acts on both alpha(1)- and
      beta-receptors in the BSTL to facilitate anxiety-like behavioral responses on the
      plus-maze but not the social interaction test, and modulates hypothalamic
      pituitary-adrenal axis activation via alpha(1)-receptors only. Together with
      previous results in which adrenergic antagonists in central amygdala attenuated
      behavioral responses on the social interaction test but not the plus-maze, these
      observations suggest the two behavioral tests measure different dimensions of
      stress reactivity, and that norepinephrine facilitates different components of
      the stress response by region- and receptor-specific mechanisms.

PMID- 12044469
TI  - Macrophage and lymphocyte invasion of dorsal root ganglia after peripheral nerve
      lesions in the rat.
AB  - The distribution of major histocompatibility complex class II (MHC II)-positive
      non-neuronal cells and T-lymphocytes was examined immunohistochemically in dorsal
      root ganglia (DRGs) up to 12 weeks following transection of one sciatic or lumbar
      spinal nerve in adult rats. Unlike within the brain, MHC II immunopositive (+)
      and T-cells are normally present within DRGs. After nerve transection, MHC II+
      cell density increased (by about four times after each lesion) in DRGs projecting
      into lesioned nerves. Subsequently the number declined after sciatic but not
      spinal nerve transection. MHC II+ cells did not contain glial markers, even when
      these were up-regulated after the lesions. Initially, MHC II+ cells lay outside
      the satellite glia but, by 11 weeks, they had moved through them to lie against
      the somata. T-cells invaded the lesioned DRGs earlier than the MHC II+ cells.
      They achieved greater numbers after spinal (30 x control) than after sciatic (12
      x control) nerve transection. They also increased in undamaged ganglia adjacent
      to the spinal nerve injury. T-cell density progressively declined after spinal
      but not sciatic nerve transection. Both cell types appeared to invade the DRGs
      initially through blood vessels and the meninges, particularly near the
      subarachnoid angle. At later stages, occasional neurones had dense aggregations
      of T-cell receptor+ and MHC II+ cells associated with them. We conclude that the
      magnitude and time course of changes in MHC II expression and T-cell numbers in
      lesioned DRGs differ from the responses within motor nuclei after axotomy. The
      influx of inflammatory cells may contribute to neurone survival in the short
      term. Their long-term presence has implications for patients. These cells have
      the potential to release excitatory cytokines that may generate ectopic impulse
      activity in sensory neurones after nerve injury and so may play a role in the
      generation of chronic neuropathic pain.

PMID- 12044470
TI  - Dopamine autoreceptor regulation of release and uptake in mouse brain slices in
      the absence of D(3) receptors.
AB  - The effects of the dopamine D(3) receptor, a putative autoreceptor, have been
      investigated by comparing behavioral and neurochemical properties of wild-type
      mice and mice with a genetic deletion of the D(3) receptor. The D(3) knock-out
      mice were modestly hyper-responsive to a novel environment relative to wild-type
      mice, and, consistent with this, quantitative in vivo microdialysis revealed
      elevated striatal dopamine extracellular levels. The dynamic actions of
      autoreceptors on electrically evoked dopamine release were examined in striatal
      brain slices from these animals and monitored with fast scan cyclic voltammetry
      at carbon-fiber microelectrodes. Quinpirole, a dopamine receptor agonist with
      potency at both D(2) and D(3) receptors, inhibited evoked dopamine in a dose
      dependent manner with a slightly higher dose required in the knock-out animals
      (EC(50) of 60+/-10 nM in wild-type animals and 130+/-40 in D(3) knock-out
      animals; both curves had a Hill slope near 2). Dopamine synthesis inhibition with
      alpha-methyl-p-tyrosine caused released dopamine levels to decrease in each
      genotype. However, regulation of secretion by autoreceptors was still operant.
      Dose-response curves to quinpirole were unchanged in D(3) knock-out tissue, but
      secretion-regulated release exhibited a Hill slope decreased to 1 in the wild
      type animals. In both genotypes, similar quinpirole-evoked increases in uptake
      rate were evident following synthesis inhibition. These data are consistent with
      the D(3) receptor having a small but significant role as a dopamine autoreceptor
      that partially regulates secretion, but not synthesis, in the caudate-putamen.

PMID- 12044471
TI  - NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual domain
      structure and a restricted expression pattern.
AB  - Ca(2+)-signalling plays a major role in regulating all aspects of neuronal
      function. Different types of neurons exhibit characteristic differences in the
      responses to Ca(2+)-signals. Correlating with differences in Ca(2+)-response are
      expression patterns of Ca(2+)-binding proteins that often serve as markers for
      various types of neurons. For example, in the cerebral cortex the EF-hand Ca(2+)
      binding proteins parvalbumin and calbindin are primarily expressed in inhibitory
      interneurons where they influence Ca(2+)-dependent responses. We have now
      identified a new family of proteins called NECABs (neuronal Ca(2+)-binding
      proteins). NECABs contain an N-terminal EF-hand domain that binds Ca(2+), but
      different from many other neuronal EF-hand Ca(2+)-binding proteins, only a single
      EF-hand domain is present. At the C-terminus, NECABs include a DUF176 motif, a
      bacterial domain of unknown function that was previously not observed in
      eukaryotes. In rat at least three closely related NECAB genes are expressed
      either primarily in brain (NECABs 1 and 2) or in brain and muscle (NECAB 3).
      Immunocytochemistry revealed that NECAB 1 is restricted to subsets of neurons. In
      cerebral cortex, NECAB 1 is highly and uniformly expressed only in layer 4
      pyramidal neurons, whereas in hippocampus only inhibitory interneurons and CA2
      pyramidal cells contain NECAB 1. In these neurons, NECAB 1 fills the entire
      cytoplasm similar to other EF-hand Ca(2+)-binding proteins, and is not
      concentrated in any particular subcellular compartment. We suggest that NECABs
      represent a novel family of regulatory Ca(2+)-binding proteins with an unusual
      domain structure and a limited expression in a subclass of neurons.

PMID- 12044472
TI  - Na(+)/Ca(2+) exchanger expression in the developing rat cortex.
AB  - The Na(+)/Ca(2+) exchanger (NCX) participates in the regulation of neuronal
      Ca(2+) homeostasis and is also believed to be involved in the neuronal responses
      to hypoxia. However, there are very limited data on how NCX mRNA and protein
      expression are regulated during brain development. In the present study, we
      sought to elucidate the developmental expression of NCX1 and NCX2 in the rat
      cortex from late fetal to adult stages using reverse transcription-polymerase
      chain reaction and western blot assays. The primers for NCX1 mRNA targeted the
      alternative splicing domain to allow differentiation between NCX1 splice
      variants. Our results show that: (1) only two NCX1 mRNA splice variants (NCX1.5
      and NCX1.4) are present in the cortex and their expression is age-dependent; (2)
      total NCX1 mRNA levels are low in fetal tissue, reach maximum density at
      postnatal day 8 and substantially decline with further maturation; (3) NCX2 mRNA
      density is significantly greater than total NCX1 mRNA for all ages and increases
      markedly during maturation from fetus/neonate to adult; and (4) NCX1 protein
      expression is lowest in late fetal cortex and reaches maximum levels after 2
      weeks postnatally, even though expression levels are not significantly different
      between newborn and adult animals. Also, we found a similar NCX1 protein trend in
      the subcortical and cerebellar regions during development. From these data we
      suggest that NCX1 and NCX2 are differentially expressed in the cortex with a
      predominance of NCX2 levels during postnatal development. We speculate that the
      developmental increase in NCX2 expression is responsible for the overall increase
      in Na(+)/Ca(2+) exchange capacity during maturation.

PMID- 12044473
TI  - Stereologic assessment of the total cortical volume occupied by amyloid deposits
      and its relationship with cognitive status in aging and Alzheimer's disease.
AB  - Although the presence of amyloid deposits is required to establish the
      neuropathologic diagnosis of Alzheimer's disease, from a clinical point of view,
      a direct contribution of these cerebral lesions to cognitive deficits is still
      controversial. The development and standardization of quantitative and accurate
      biochemical and neuropathologic methods may be critical to improve the postmortem
      diagnosis and clinicopathologic correlations. Here, we used a point counting
      method, based on the Cavalieri principle, to estimate the volume occupied by
      amyloid deposits in a discrete region of the prefrontal cortex and in the
      hippocampal formation, in brains from patients with cognitive status ranging from
      normal to severely demented. We demonstrate that the assessment of the total
      volume occupied by the amyloid deposits in the entorhinal cortex and subiculum
      can be considered an effective predictor of dementia severity. We also reveal the
      existence of a high degree of regional and interindividual heterogeneity in
      amyloid distribution and relative volume. Our data suggest that even though a
      correlation was observed between the stereologic point counting method and a non
      stereologic random field thresholding approach, in most cases non-stereologic
      methods may not provide adequate samples of the tissue and may lead to unreliable
      estimates of amyloid burden due to the inhomogeneous distribution of amyloid in
      the cerebral cortex and the large variability among brains.

PMID- 12044474
TI  - Developmental expression of carbonic anhydrase-related proteins VIII, X, and XI
      in the human brain.
AB  - Three cDNA homologues of carbonic anhydrase with unknown biological functions
      have been reported: carbonic anhydrase-related proteins (CA-RP) VIII, X, and XI.
      In the present study, we produced monoclonal antibodies to these CA-RPs and
      studied their regional and cellular distributions in the human adult and fetal
      brains by immunohistochemical analysis. In the adult brain, CA-RP VIII was
      expressed in the neural cell body spreading to most parts of the brain. CA-RP X
      was expressed in the myelin sheath and its expression was shown in the cytoplasm
      of cultured tumor cells by immunocytochemical analysis. CA-RP XI was expressed in
      the neural cell body, neurites, and astrocytes in relatively limited regions of
      the brain. In the fetal brain, CA-RP VIII and XI were expressed in the
      neuroprogenitor cells in the subventricular zone as early as the 84th day of
      gestation and subsequently detected in the neural cells migrating to the cortex.
      CA-RP X first appeared in the neural cells in the cortex at the 141st day. In the
      choroid plexus, the epithelial cells gave CA-RP VIII and XI expressions in both
      adult and fetal brains. From the findings in the present study on the
      distribution and the developmental expression of CA-RP VIII, X, and XI in the
      human brain we suggest that these CA-RPs play roles in various biological process
      of the CNS.

PMID- 12044475
TI  - Evolution of hippocampal epileptic activity during the development of hippocampal
      sclerosis in a mouse model of temporal lobe epilepsy.
AB  - Unilateral intrahippocampal injection of kainic acid in adult mice reproduces
      most of the morphological characteristics of hippocampal sclerosis (neuronal
      loss, gliosis, reorganization of neurotransmitter receptors, mossy fiber
      sprouting, granule cell dispersion) observed in patients with temporal lobe
      epilepsy. Whereas some neuronal loss is observed immediately after the initial
      status epilepticus induced by kainate treatment, most reorganization processes
      develop progressively over a period of several weeks. The aim of this study was
      to characterize the evolution of seizure activity in this model and to assess its
      pharmacological reactivity to classical antiepileptic drugs. Intrahippocampal
      electroencephalographic recordings showed three distinct phases of paroxystic
      activity following unilateral injection of kainic acid (1 nmol in 50 nl) into the
      dorsal hippocampus of adult mice: (i) a non-convulsive status epilepticus, (ii) a
      latent phase lasting approximately 2 weeks, during which no organized activity
      was recorded, and (iii) a phase of chronic seizure activity with recurrent
      hippocampal paroxysmal discharges characterized by high amplitude sharp wave
      onset. These recurrent seizures were first seen about 2 weeks post-injection.
      They were limited to the injected area and were not observed in the cerebral
      cortex, contralateral hippocampus or ipsilateral amygdala. Secondary propagation
      to the contralateral hippocampus and to the cerebral cortex was rare. In addition
      hippocampal paroxysmal discharges were not responsive to acute carbamazepine,
      phenytoin, or valproate treatment, but could be suppressed by diazepam. Our data
      further validate intrahippocampal injection of kainate in mice as a model of
      temporal lobe epilepsy and suggest that synaptic reorganization in the lesioned
      hippocampus is necessary for the development of organized recurrent seizures.

PMID- 12044476
TI  - Down-regulation of basal Fos expression at nucleus tractus solitarii underlies
      restoration of baroreflex response after antihypertensive treatment in
      spontaneously hypertensive rats.
AB  - Antihypertensive therapy not only normalizes the elevated blood pressure but also
      restores the reduced baroreceptor reflex response associated with hypertension,
      although the underlying mechanism is not fully understood. We assessed the
      hypothesis that a reversal of the enhanced basal Fos expression seen during
      hypertension in nucleus tractus solitarii, the terminal site of baroreceptor
      afferents, underlies the restoration of baroreceptor reflex sensitivity after
      antihypertensive treatment. Male adult spontaneously hypertensive or normotensive
      Wistar-Kyoto rats received for 3 weeks captopril (100 mg/kg/day) added to their
      drinking water. Evaluated subsequently under pentobarbital anesthesia, captopril
      treated spontaneously hypertensive rats exhibited significantly lowered systolic
      blood pressure and restoration of the sensitivity in baroreceptor reflex control
      of heart rate to levels comparable with Wistar-Kyoto rats. Reverse transcription
      polymerase chain reaction analysis and immunohistochemical evaluation revealed
      concomitant down-regulation of basal expression in nucleus tractus solitarii of c
      fos gene at both mRNA and protein levels. Captopril treatment, on the other hand,
      elicited no discernible effect on systolic blood pressure, cardiac baroreceptor
      reflex sensitivity or basal expression of Fos protein at the nucleus tractus
      solitarii of normotensive Wistar-Kyoto rats. From these findings we suggest that
      a down-regulation of basal Fos expression in nucleus tractus solitarii may
      contribute to the restoration of baroreceptor reflex sensitivity in spontaneously
      hypertensive rats that received antihypertensive treatment such as captopril.

PMID- 12044477
TI  - Endogenous opioid regulation of stress-induced oxytocin release within the
      hypothalamic paraventricular nucleus is reversed in late pregnancy: a
      microdialysis study.
AB  - Oxytocin secretion into blood in response to swim stress is differentially
      regulated by endogenous opioids in virgin and pregnant rats. Here, the influence
      of endogenous opioids on oxytocin release within the hypothalamic paraventricular
      and supraoptic nuclei was investigated using microdialysis in virgin and pregnant
      (day 19-21) rats. Rats fitted with a U-shaped microdialysis probe 3 days before
      testing were injected with naloxone (5 mg/kg body weight, s.c.) or vehicle
      (sterile saline) and, 3 min later, were forced to swim (10 min at 19 degrees C).
      Within the paraventricular nucleus, basal and stimulated oxytocin release did not
      significantly differ between vehicle-treated virgin and pregnant rats. After
      naloxone, local oxytocin release in response to swimming was lowered in virgin
      rats (P<0.01), whereas it was further increased in pregnant rats (P<0.01). Within
      the supraoptic nucleus, basal oxytocin release was significantly lower in
      pregnant compared to virgin rats (P<0.01). Forced swimming induced a similar rise
      in intranuclear oxytocin release in both vehicle-treated virgin and pregnant
      rats, but peak levels were still higher in the virgin controls. In contrast to
      the paraventricular nucleus, naloxone did not alter swim-induced oxytocin release
      within the supraoptic nucleus either in virgin or pregnant rats. Vasopressin
      release in the paraventricular nucleus was also increased by forced swimming but
      there was no effect of pregnancy or naloxone on it. In summary, in pregnancy,
      basal and stress-induced oxytocin release within the paraventricular nucleus was
      not changed, whereas it was blunted within the supraoptic nucleus. Further,
      within the paraventricular nucleus the excitatory effect of endogenous opioids on
      local oxytocin release seen in virgins was switched into an inhibitory action in
      pregnancy. In contrast, endogenous opioids were evidently not involved in the
      regulation of swim-induced oxytocin release within the supraoptic nucleus either
      in virgin or pregnant rats. Thus, pregnancy-related neuroendocrine plasticity
      also includes site-specific functional alterations in opioid receptor-mediated
      actions in the hypothalamus.

PMID- 12044478
TI  - Opioid receptor gene expression in dopamine transporter knock-out mice in adult
      and during development.
AB  - Dopamine transporter knock-out mice display locomotor hyperactivity due to
      increased extracellular striatal levels of dopamine. Hyperdopaminergic activity
      within this mesolimbic pathway is involved in the rewarding properties of
      morphine which are also increased in these mice. Due to the hyperdopaminergia,
      profound alterations in gene expression for dopamine receptors and neuropeptides
      are observed in the caudate putamen and nucleus accumbens. Here we investigated
      (1) the levels of mu-, delta- and kappa-opioid receptors mRNAs in normal mice
      from gestational day 13 (G13) to adult, and (2) the adaptive changes in the
      expression of these receptors in mice lacking the dopamine transporter. Our
      results show that, in wild-type mice, mu-opioid receptor mRNA expression appears
      early during development (G13) with a homogeneous distribution that evolves
      towards a patchy distribution in adult. Delta-opioid receptor mRNA appears only
      at G17 and kappa-opioid receptor mRNA is not observed before adulthood. The
      levels of delta-opioid receptor mRNA are not modified during development in knock
      out mice compared to wild-type, but are increased in adult caudate putamen (+39%,
      P<0.05) and nucleus accumbens (+66%, P<0.05) at a time when these receptors are
      believed to be functional. The mu- and kappa-opioid receptors mRNA levels are not
      modified in the adult knock-out mice. In addition, we observed no differences in
      any opioid receptor mRNA level in dopamine transporter knock-out mice during
      prenatal ontogeny compared to wild-type. Our results constitute a detailed
      neuroanatomical description of opioid receptor mRNA expression from the time of
      their appearance during prenatal development until adulthood. Furthermore, we
      show here that chronic constitutive hyperdopaminergia only affects delta-opioid
      receptor mRNA levels in adult. Even if the propensity of knock-out mice to show
      increased rewarding properties to morphine seems to be mainly due to the
      substantial and further increase in hyperdopaminergic activity following drug
      treatment, the involvement of increased delta-opioid receptor mRNA levels in this
      behavior remains to be elucidated.

PMID- 12044479
TI  - Regeneration of acutely and chronically injured descending respiratory pathways
      within post-traumatic nerve grafts.
AB  - Central respiratory neurons, which are acutely axotomized by peripheral nerve
      grafts implanted at the level of the descending respiratory pathways within the
      C2 spinal cord, can regenerate their axons within the grafts and still transmit
      normal physiological messages [Decherchi et al., 1996. Exp. Neurol. 137, 1-14].
      The present work investigated the extent to which mature central neurons, acutely
      or chronically axotomized by a spinal lesion, still maintain the potential to
      regenerate an axon following post-traumatic nerve grafting within supra-lesional
      spinal structures and remained functional. This study is an extension of earlier
      work employing the more chronic lesions, that investigated whether respiratory
      neurons chronically axotomized by a spinal cord injury can retain the ability to
      regenerate their axonal process within a post-traumatic peripheral nerve graft.
      Here implantation was performed into the supra-lesional ventrolateral part of the
      ipsilateral C2 spinal cord (at the level of the descending respiratory pathways)
      previously hemisected at the C3 level. In the present study, these post-traumatic
      peripheral nerve grafts were performed either acutely (group I, n=15, 2.5 h post
      injury: acute conditions) or chronically (group II, n=17, 3 weeks; group III,
      n=6, 3 months: chronic conditions) after the injury.Electrophysiological
      recording of teased filaments (n=2362) within the post-traumatic peripheral nerve
      grafts revealed the presence of regenerated nerve fibers with spontaneous unitary
      impulse traffic (graft units, n=954) in all animals. These graft units were
      respiratory (n=247) and non-respiratory (n=707). Respiratory discharges
      originated from central respiratory neurons which remained functional with
      preserved afferent connections. Except for the group III, post-traumatic C2
      peripheral nerve grafts of the groups I and II contained a significantly higher
      occurrence rate (13.2+/-2% and 11.6+/-1.9%) of respiratory units than C2 spinal
      peripheral nerve grafts (5.9+/-1.6%) realized without previous CNS injury. The
      main conclusion of our study is that for a prolonged period of 3 weeks following
      a spinal cord injury, central respiratory neurons have the potential to remain
      functional and to regenerate their axonal process within post-traumatic
      peripheral nerve grafts inserted rostrally to the spinal damage. This indicates
      that supra-lesional post-traumatic nerve grafts may constitute an efficient
      delayed strategy for inducing axonal regrowth of chronically axotomized adult
      central neurons. This suggests that surgical intervention which is not always
      possible immediately after a spinal cord injury may be satisfactorily carried out
      after an appropriate delay.

PMID- 12044480
TI  - Nociceptin/orphanin FQ receptors modulate glutamate extracellular levels in the
      substantia nigra pars reticulata. A microdialysis study in the awake freely
      moving rat.
AB  - Intracerebral microdialysis was employed in awake freely moving rats to
      investigate the effects of nociceptin/orphanin FQ receptor ligands on glutamate
      extracellular levels in the substantia nigra pars reticulata. Nociceptin/orphanin
      FQ, ineffective at 0.1 microM, induced a prolonged stimulation of nigral
      glutamate levels at 1 and 10 microM (mean effect of 137+/-9 and 167+/-13%,
      respectively, of basal values). These effects were prevented by the novel
      nociceptin/orphanin FQ receptor antagonist [Nphe(1)]nociceptin/orphanin FQ(1
      13)NH(2) (100 and 300 microM, respectively) but not by the non-selective opioid
      receptor antagonist naloxone (10 microM). [Nphe(1)]nociceptin/orphanin FQ(1
      13)NH(2) (100 microM) inhibited by itself glutamate outflow (maximal reduction to
      71+/-4%) while naloxone was ineffective. The nociceptin/orphanin FQ receptor
      ligand [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin/orphanin FQ(1-13)NH(2) also
      facilitated glutamate outflow at 10 microM (mean effect of 145+/-10%).
      Intranigral perfusion with tetrodotoxin (1 microM) or with the dopamine D(2)
      receptor antagonist raclopride (1 microM), failed to affect basal glutamate
      output and prevented the facilitatory effect of nociceptin/orphanin FQ (10
      microM). However, perfusion with the GABA(A) receptor antagonist bicuculline (10
      microM) increased local glutamate extracellular levels by itself and attenuated
      the effect of the peptide. Our data suggest that nociceptin/orphanin FQ increases
      glutamate extracellular levels in the substantia nigra pars reticulata via
      activation of nociceptin/orphanin FQ receptors located on non-glutamatergic,
      possibly dopaminergic and GABAergic, neuronal elements.

PMID- 12044481
TI  - The IkappaB kinase inhibitor sulfasalazine impairs long-term memory in the crab
      Chasmagnathus.
AB  - Evidence for the participation of Rel/NF-kappaB transcription factors in long
      term memory has recently been reported in the context-signal learning paradigm of
      the crab Chasmagnathus, in which a high correlation between long-term memory
      formation and NF-kappaB activation was observed. Two components of the NF-kappaB
      pathway in the crab brain have now been identified by cross-immunoreactivity
      using mammalian antibodies for IkappaB-alpha and IkappaB kinase alpha.
      Furthermore, IkappaB kinase-like phosphotransferase activity, which was inhibited
      by the IkappaB kinase inhibitor sulfasalazine, was detected in brain extracts. We
      have evaluated the effect of sulfasalazine administration on long-term memory
      tested at 48 h. Amnesia was found when sulfasalazine was administered pre
      training and 5 h after training but not at 0 or 24 h after training. Thus, two
      periods for sulfasalazine-induced amnesia were found in coincidence with the two
      phases of NF-kappaB activation previously described (immediately and 6 h after
      training). The cyclooxygenase inhibitor indomethacin did not induce amnesia when
      administered pre-training. Thus, the possibility that sulfasalazine induces
      amnesia by means of cyclooxygenase inhibition is unlikely to be tenable. In vivo
      sulfasalazine inhibition of basal NF-kappaB activity was found between 30 and 45
      min after injection, as assessed by electrophoretic mobility shift assay. On the
      other hand, in vivo sulfasalazine administration 6 h after training inhibited the
      second phase of training-induced NF-kappaB activation, providing evidence that
      the sulfasalazine effect on memory is due to a direct effect of the drug on the
      NF-kappaB pathway. These results provide the first evidence that IkappaB kinase
      and NF-kappaB activation are necessary for memory formation.

PMID- 12044482
TI  - The effects of galanin on long-term synaptic plasticity in the CA1 area of rodent
      hippocampus.
AB  - Learning and memory involve complex changes in neuronal excitability including
      long-lasting synaptic plasticity of glutamatergic synapses. The observation that
      the neuropeptide galanin affects performance in a number of behavioural models
      predicts that galanin should affect synaptic processes underlying learning. The
      present study in rat and mouse hippocampal slices now demonstrates that galanin
      inhibits long-term potentiation induced by both tetanic and theta-burst
      stimulation in both apical and basal dendrites of CA1 pyramidal neurones but does
      not affect long-term depression. This selective effect on long-term potentiation
      does not appear to be mediated through inhibition of N-methyl-D-aspartate or
      metabotropic glutamate receptor function, but likely resides downstream of
      receptor activation, possibly at the level of the kinase cascade that converts
      short-term into long-term potentiation. Our results indicate possible mechanisms
      by which the neuropeptide galanin may act at the molecular level to influence
      learning and memory in vertebrates.

PMID- 12044484
TI  - Spatio-temporal plasticity of cortical receptive fields in response to repetitive
      visual stimulation in the adult cat.
AB  - Many psychophysical experiments on perceptual learning in humans show increases
      of performance that are most probably based on functions of early visual cortical
      areas. Long-term plasticity of the primary visual cortex has so far been shown in
      vivo with the use of visual stimuli paired with electrical or pharmacological
      stimulation at the cellular level. Here, we report that plasticity in the adult
      visual cortex can be achieved by repetitive visual stimulation. First, spatial
      receptive field profiles of single units (n=38) in area 17 or 18 of the
      anesthetized cat were determined with optimally oriented flashing light bars.
      Then a conditioning protocol was applied to induce associative synaptic
      plasticity. The receptive field center and an unresponsive region just outside
      the excitatory receptive field were synchronously stimulated ('costimulation',
      repetition rate 1 Hz; for 10-75 min). After costimulation the receptive field and
      its adjacent regions were mapped again. We observed specific increases of the
      receptive field size, changes of the receptive field subfield structure as well
      as shifts in response latency. In 37% of the cells the receptive field size
      increased specifically towards the stimulated side but not towards the non
      stimulated opposite side of the receptive field. In addition, changes in the
      relative strength and size of the on and off subfield regions were observed.
      These specific alterations were dependent on the level of neuronal activity
      during costimulation. During recovery, the new responses dropped down to 120% of
      the preconditioning value on average within 103 min; however, the decay times
      significantly depended on the response magnitude after costimulation. In the
      temporal domain, the latency of new responses appeared to be strongly influenced
      by the latency of the response during costimulation.Twenty-nine percent of the
      units displayed no receptive field enlargement, most likely because the activity
      during costimulation was significantly lower than in the cases with enlarged
      receptive fields. An unspecific receptive field enlargement towards both the
      stimulated and non-stimulated side was observed in 34% of the tested cells. In
      contrast to the cells with specifically enlarged receptive fields, the unspecific
      increase of receptive field size was always accompanied by a strong increase of
      the general activity level. We conclude that the receptive field changes
      presumably took place by strengthening of synaptic inputs at the recorded cells
      in a Hebbian way as previously shown in the visual cortex in vitro and in vivo.
      The observed receptive field changes may be related to preattentive perceptual
      learning and could represent a basis of the 'filling in' of cortical scotomas
      obtained with specific training procedures in human patients suffering from
      visual cortex lesions.

PMID- 12044483
TI  - Group I metabotropic glutamate receptor inhibition selectively blocks a prolonged
      Ca(2+) elevation associated with age-dependent excitotoxicity.
AB  - It has been recognized for some years that a prolonged Ca(2+) elevation that is
      predictive of impending cell death develops in cultured neurons following
      excitotoxic insult. In addition, neurons exhibit enhanced sensitivity to
      excitotoxic insult with increasing age in culture. However, little is known about
      the processes that selectively regulate the post-insult Ca(2+) elevation and
      therefore, it remains unclear whether it is associated specifically with age
      dependent toxicity.Here, we tested the hypothesis that a group I metabotropic
      glutamate receptor antagonist selectively modulates the prolonged Ca(2+)
      elevation in direct association with its protective effects against
      excitotoxicity. Rat hippocampal cultures of two ages (8-9 and 21-28 days in
      vitro) were exposed to a 5-min glutamate insult (400 microM in younger and 10
      microM in older cultures) sufficient to kill >50% of the neurons, and were
      treated with vehicle or the specific group I metabotropic glutamate receptor
      antagonist 1-aminoindan-1,5-dicarboxylic acid (AIDA; 1 mM), throughout and
      following the insult. Neuronal survival was quantified 24 h after insult. In
      parallel studies, neurons of similar age in culture were imaged ratiometrically
      with a confocal microscope during and for 60 min after the glutamate insult. A
      large post-insult Ca(2+) elevation was present in older but not most younger
      neurons. The N-methyl-D-aspartate receptor antagonist, MK-801, blocked the Ca(2+)
      elevation both during and following the insult. In contrast, AIDA blocked only
      the post-insult prolonged Ca(2+) elevation in older neurons. Moreover, AIDA was
      neuroprotective in older but not younger cultures. From these results we suggest
      that the post-insult Ca(2+) elevation is regulated differently from the Ca(2+)
      elevation during glutamate insult and is modulated by group I metabotropic
      glutamate receptors. Further, the prolonged Ca(2+) elevation appears to be
      directly linked to an age-dependent component of vulnerability.

PMID- 12044485
TI  - The localization of two voltage-gated calcium channels in the pyloric network of
      the lobster stomatogastric ganglion.
AB  - Voltage-gated calcium channels are critical to all aspects of nervous system
      function, with differing roles within the neuronal somata, at synaptic terminals,
      and at the neuromuscular junction. We have developed antibodies against two
      voltage-gated Ca(2+) channel genes from the spiny lobster, Panulirus interruptus,
      which are homologous to the Drosophila Ca1A (a P/Q-type channel) and Ca1D (an L
      type channel) genes. Using these antibodies, we have found that each channel
      shows unique patterns of localization within the stomatogastric nervous system.
      Both antibodies stain somata of most of the neurons in the pyloric network to
      varying degrees. The high degree of variability in staining intensity within
      individual pyloric cell classes supports the hypothesis of Golowasch et al.
      (1999a,b) that individual cells can vary in their composition of ionic currents
      and still have similar firing properties. Anti-Ca1A stains structures in the
      neuropil, some of which are terminals of axons descending from higher ganglia;
      however, the majority of these are neither neurites nor blood vessels, but may
      instead be glial cells or other support elements. Anti-Ca1A labeling was also
      prominent in the peripheral axons of pyloric motoneurons as they enter muscles,
      indicating that this channel may be involved in regulation of synaptic
      transmission onto the foregut muscles. Anti-Ca1D does not label neurites in the
      neuropil of the stomatogastric ganglion. It stains glial cells in the
      stomatogastric ganglion in the region of their nuclei, presumably from protein
      being produced in the perinuclear rough endoplasmic reticulum, en route to the
      glial cell periphery. While anti-Ca1D labeling is seen in a patchy distribution
      along peripheral pyloric axons, it was never seen near the muscle. We conclude
      that the localization of these two calcium channels is tightly controlled within
      the stomatogastric nervous system, but we cannot conclusively demonstrate that
      Ca1A and/or Ca1D channels play roles in synaptic integration within the
      stomatogastric ganglion.

PMID- 12044486
TI  - Deltamethrin differentially affects neuronal subtypes in hippocampal primary
      culture.
AB  - The effects of deltamethrin on neuronal development and survival were studied
      using primary mouse hippocampal neurons in culture. Repeated applications of
      deltamethrin (between 2 nM and 2000 nM) decreased the number of neurons by 16
      40%, respectively. Neuronal death was accompanied by an overall decrease of
      synaptic proteins. Deltamethrin treatment increased the K(+)-stimulated release
      of amino acid transmitters, GABA and glutamate. The release of the latter might
      also contribute to neuronal damage. A considerable number of neurons survived
      treatment with high concentrations of deltamethrin (200-2000 nM) and still
      displayed characteristics of mature neurons such as synaptic contacts or the
      expression of members of the Kv1 channel family. When analyzing subtypes of
      neurons calbindin- as well as somatostatin-positive neurons decreased by 50%
      after repeated treatment with 2 nM deltamethrin. Under the same conditions
      neuropeptide Y-positive neurons were up-regulated by 250%.Taken together these
      data show that deltamethrin at concentrations relevant in human toxicology
      differentially affects survival of neuronal subtypes by exerting either
      deleterious or supportive effects. We conclude that deltamethrin disturbs fine
      tuning of neuronal efficiency in neuronal networks and might also interfere with
      the correct wiring during development.

PMID- 12044487
TI  - Rhodnius prolixus vitellin is composed of three different populations: comparison
      with vitellogenin.
AB  - Rhodnius prolixus oocyte extracts were chromatographed on an ion exchange column
      in order to purify vitellin (VT). Three VT heterogeneous populations were
      identified and named VT(1), VT(2), and VT(3) according to their order of elution
      from the column. The phosphate content of each population was determined, after
      lipid extraction, and a heterogeneous distribution was found: VT(1) being the
      less phosphorylated (50 mol P/mol protein) and VT(3) the heavily phosphorylated
      population (281 mol P/mol protein). Analysis of radioactivity associated with
      each VT population purified from animals fed with (32)Pi showed the same
      phosphorylation profile. Due to the fact that vitellogenin is the known precursor
      of VT, we have also chromatographed 32P-VG in the same way as we purified VT.
      Only one VG's population was detected and resembled to VT(3) with respect to its
      elution profile. All VT populations contain the same neutral lipids, but they
      were heterogeneous with respect to phospholipid composition. VT(1) presents
      phosphatidylcholine and phosphatidylethanolamine whereas VT(2) and VT(3) also
      showed cardiolipin and probably phosphatidylserine. Sugar composition of VT(2)
      and VT(3) includes mannose as the main associated carbohydrate but VT(1) also
      contains glucose resembling VG. Although VG and VT are similar with respect to
      the elution profile, their sugar composition is different. These results suggest
      a post-endocytosis processing on VG molecule. The possible biological function of
      VT heterogeneous populations is discussed.

PMID- 12044488
TI  - Leucine methyl ester is a powerful allosteric activator of the neutral amino acid
      cotransport system in Bombyx mori larval midgut.
AB  - We have identified three methyl esters that have a potent stimulatory effect on
      the cotransport system responsible for the absorption of most essential amino
      acids in the silkworm Bombyx mori. L-Leucine methyl ester, the most powerful
      activator, determined a large dose-dependent, K(+)-independent increase of
      leucine uptake into midgut brush border membrane vesicles. Kinetic experiments
      revealed non-essential mixed-type activation, with K(a) values of 27+/-2 and 47+/
      8 microM in the presence and in the absence of K(+), respectively. The activation
      increased K(m) twofold, and V(max) up to 18-fold depending upon the experimental
      conditions. Leucine uptake mediated by the amino acid uniport appears to be
      unaffected by the activator.

PMID- 12044489
TI  - Analysis of venom constituents from the parasitoid wasp Pimpla hypochondriaca and
      cloning of a cDNA encoding a venom protein.
AB  - Venom from Pimpla hypochondriaca, an endoparasitoid of pupae, was size
      fractionated using gel filtration chromatography and analysed by SDS-PAGE in the
      presence and absence of reducing agent. A complex mixture of more than 20 venom
      constituents was identified which ranged in M(r) between approximately 5 and 100
      kDa. Venom from a wide range of size fractions inhibited the motility of larval
      haemocytes and prevented the formation of cell aggregates when analysed in vitro,
      indicating that anti-haemocytic activity is mediated by multiple venom
      components. Sephadex A25 beads injected into the haemocoel of pupae were
      encapsulated within 24h. This reaction was abolished when the pupae were injected
      with 30 microg of venom protein, equivalent to one-fifth of a venom sac, 1h prior
      to implantation of the beads, confirming that venom suppresses encapsulation in
      pupae. Using random 5' end sequencing of a P. hypochondriaca venom gland cDNA
      library, we have isolated a cDNA encoding a 25.3 kDa protein containing a signal
      peptide and having sequence similarity to serine proteases. The N-terminal
      sequence of six residues from two venom proteins of 28 and 30 kDa was the same
      and identical to amino acids encoded by the cDNA, confirming that two mass forms
      of the protein are secreted into the venom sac. The N-terminal sequence of both
      venom proteins began nine residues towards the C terminus following the predicted
      signal sequence cleavage site, suggesting that the proteins are proteolytically
      processed before or during storage in the venom sac. The general applicability of
      using random 5' sequencing to identify cDNAs encoding secretory products is
      discussed.

PMID- 12044490
TI  - The control of BhB10-1 gene expression in the salivary gland of Bradysia hygida
      (Diptera, Sciaridae) is disrupted in vivo by a delayed effect of cycloheximide.
AB  - BhB10-1 is an amplified gene present in DNA puff B10. This gene is very active in
      the salivary gland regions S1 and S3 at the end of the larval development. Two
      transcripts of this gene, 1.3 and 1.1 kb in size, were detected. A secretory
      protein, SP23, is the product of BhB10-1. In this work, we present evidence
      supporting the hypothesis that a biphasic process of mRNA degradation is an
      important component in the control of BhB10-1 gene expression. The 1.3 kb
      transcript, by a process of poly(A) tail shortening, is converted to the inactive
      transcript of 1.1 kb which is detected during and after the period of SP23
      expression. Cycloheximide in very low concentration, if applied at a proper time,
      can disrupt this process leading to extended periods of 1.3 kb RNA detection and
      SP23 synthesis. A tentative model is proposed to explain this phenomenon.

PMID- 12044491
TI  - Cloning and partial characterization of a Boophilus microplus (Acari: Ixodidae)
      glutathione S-transferase.
AB  - A cDNA of glutathione S-transferase (GST) was isolated from a cDNA library of
      salivary glands of Boophilus microplus. The recombinant protein was purified by
      glutathione affinity chromatography and assayed upon the chromogenic substrate
      CDNB. The 864 bp cloned fragment was sequenced and showed an open reading frame
      coding for a protein of 220 amino acids. Expression of the GST gene was tested by
      RT-PCR in tick tissues and larvae mRNA. Comparison of the deduced amino acid
      sequence with GSTs from other species revealed that the enzyme is closely related
      to the mammalian class mu GSTs.

PMID- 12044492
TI  - Identification of two new cytochrome P450 genes and their 5'-flanking regions
      from the housefly, Musca domestica.
AB  - Two new cytochrome P450 cDNAs, named CYP28B1 and CYP4G13v2, and their 5'-flanking
      regions were cloned and sequenced from a housefly strain, ALHF. The cDNA
      sequences of CYP28B1 and CYP4G13v2 have open reading frames of 1449 and 1653
      nucleotides encoding proteins of 483 and 551 amino acid residues, respectively.
      Sequence analysis shows that both CYP28B1 and CYP4G13v2 putative P450 proteins
      contain: (1) a highly hydrophobic N terminus; (2) a P450 protein signature motif,
      FXXGXRXCXG, known as the important ligand for heme binding; (3) a motif,
      YXXAXXXEXXR, which is a conserved P450 sequence coinciding with Helix K; and (4)
      a typical aromatic sequence, A(1)XXPXXA(2)XPXBA(3), which is conserved within
      most P450s. The 5'-flanking regions of CYP28B1 (>2kb) and CYP4G13v2 (>1 kb) were
      isolated from adaptor-ligated ALHF genomic DNA libraries. The transcription start
      points of CYP28B1 and CYP4G13v2 were mapped to 176 and 163 nucleotides upstream
      of the ATG translation start codon within the conserved arthropod promoter
      elements of TCATT and ACAGT, respectively. Possible regulatory binding sites for
      general transcription factors, Sp1 and AP1, were mapped in the 5' promoter
      regions of CYP28B1 whereas TFIID and Oct-1 were mapped in CYP4G13v2. Five
      conserved cis-acting elements for tissue- or cell-specific transcription
      regulatory factors were identified in the promoter regions of both P450 genes. A
      structure of five 153-nucleotide (nt) highly identical repeats and two partial
      repeat sequences were found in the promoter region of CYP28B1. The homologous
      (90% identity) sequences of the 153-nt repeat were also found in the promoter
      region of CYP4G13v2. The homologous sequences of the repeat in other insect P450
      gene promoter regions are discussed.

PMID- 12044493
TI  - Molecular cloning and characterization of a greenbug (Schizaphis graminum) cDNA
      encoding acetylcholinesterase possibly evolved from a duplicate gene lineage.
AB  - An acetylcholinesterase (AChE, EC 3.1.1.7) cDNA was cloned and characterized from
      a greenbug (Schizaphis graminum (Rondani)) cDNA library. The complete cDNA (3283
      bp) contains a 2028-bp open reading frame encoding 676 amino acid residues. The
      putative AChE preproenzyme has a 17 amino acid signal peptide, a 78 amino acid
      activation peptide and a mature enzyme of 581 amino acid residues. The first nine
      amino acid residues (YTSDDPLII) that were determined by sequencing the N-terminus
      of a 72-kDa AChE purified from the greenbug matched the nine residues deduced
      from the cDNA. The key amino acid residues, including the three residues Ser206
      (200 in Torpedo), Glu332 (327) and His446 (440) forming a catalytic triad, three
      pairs of cysteine putatively forming intrachain disulfide bonds, and 10 out of
      the 14 aromatic residues lining the active site gorge of the Torpedo AChE, are
      conserved. However, Ser336 (Phe331) in the greenbug substituted an aromatic amino
      acid residue that is conserved in all other known AChEs. Northern blot analysis
      of mRNA revealed a 3.7-kb transcript, and Southern blot analysis suggested a
      single copy of this gene in the greenbug. The deduced amino acid sequence is most
      similar to AChE1 of the nematodes Caenorhabditis briggsae and C. elegans with 43%
      identity. Phylogenetic analysis showed that the greenbug AChE formed a cluster
      with those of nematodes, a squid and ticks, and grouped out of the insect
      cluster. This result suggests that the cloned gene evolved from a different
      duplicate gene lineage of insect AChEs.

PMID- 12044494
TI  - Dual cellulose-digesting system of the wood-feeding termite, Coptotermes
      formosanus Shiraki.
AB  - The distribution of endo-beta-1,4-glucanase (EG) components in the digestive
      system of the wood-feeding termite, Coptotermes formosanus Shiraki, was
      investigated by zymogram analysis using polyacrylamide gel electrophoresis,
      followed by N-terminal protein sequencing. EG components similar to glycoside
      hydrolase family (GHF) 9 members were restricted to the salivary glands, the
      foregut, and the midgut, whereas components similar to GHF7 members were confined
      to the hindgut where numerous cellulolytic flagellates were harbored. RT-PCR
      experiments revealed that five GHF9 EG mRNAs (1348 bp) homologous to other
      termite EGs were expressed in the salivary glands and the midgut. The crude
      extract prepared from the midgut as well as that from the hindgut produced
      glucose from crystalline cellulose. These data suggest that C. formosanus has two
      independent cellulose-digesting systems: one in the midgut where cellulose
      digestion is accomplished by endogenous cellulases and the other in the hindgut
      which makes use of other cellulases possibly from symbiotic flagellates.

PMID- 12044495
TI  - Identification and characterization of genes differentially expressed in the
      testis/vas deferens of the fed male tick, Amblyomma hebraeum.
AB  - Most ixodid ticks must feed for at least a few days to complete gonad maturation.
      Substances produced by the mature male gonad, and carried in the spermatophore,
      induce physiological changes in the female that lead to engorgement and
      oviposition. To begin defining the molecular phenotype at this stage of male
      development, we differentially cross-screened a cDNA library made from the testis
      and vas deferens of fed ticks (Amblyomma hebraeum Koch) and isolated 35 genes
      that were putatively up-regulated in tissues of fed compared to unfed animals.
      While the majority of these were novel, two clones, AhT/VD16 and AhT/VD146,
      yielded homologies (53 and 44%) to known genes (acylphosphatse and 9.0 kD
      Drosophila melanogaster basic protein, respectively). Results of Northern blot
      analysis of AhT/VD16 and AhT/VD146 demonstrate that both clones hybridized with
      mRNA transcripts that were up-regulated in the testis/vas deferens of fed
      compared to unfed males. In addition, hybridization of clone AhT/VD16 to water
      strider (Gerris argentatus) genomic DNA, and sequence similarities to mammalian
      acylphosphatase, suggest that it represents an evolutionarily conserved sequence.

PMID- 12044496
TI  - Trichoplusia ni gloverin, an inducible immune gene encoding an antibacterial
      insect protein.
AB  - By using differential display PCR, we obtained a cDNA clone encoding a gloverin
      homologue from the cabbage looper, Trichoplusia ni. The expression of the gene
      was induced by bacterial infections. The gene codes for a 174 amino acid residue
      protein, including a signal sequence and a prosegment. The deduced mature protein
      is 14 kDa and shows 58% and 49% identity to P2 from Helicoverpa armigera and to
      Hyalophora gloveri gloverin, respectively. The protein was detected in hemolymph
      and hemocytes from bacteria-immunized animals. We expressed gloverin using the
      baculovirus expression system. N-terminal amino acid sequence analysis showed
      that the purified protein contained a propart. This progloverin inhibited the
      growth of E. coli and the activity is comparable to that of H. gloveri mature
      gloverin. Processing of progloverin was possible in vitro, using human furin.

PMID- 12044497
TI  - Characterization of the proteolytic enzymes in the midgut of the European
      Cockchafer, Melolontha melolontha (Coleoptera: Scarabaeidae).
AB  - In previous studies we showed that the resistance of the European Cockchafer,
      Melolontha melolontha, towards the Scarab specific Cry8C toxin of Bacillus
      thuringiensis japonensis strain Buibui is due to the complexity of proteinases in
      the midgut of the pest insect. In this study these proteinases were identified
      and characterized using a combination of synthetic substrates and specific
      inhibitors in zymograms, activity blots, and photometric/fluorometric assays. In
      the midgut juice three trypsin-like and three elastase-like serine proteinases
      are predominantly present. In addition, two metalloendoproteinases were detected.
      At least one of them is most likely to belong to the astacin family, proteinases
      which normally do not play a role in general protein digestion outside the
      decapod crustacean. Furthermore, a free aminopeptidase as well as a membrane
      associated aminopeptidase, isolated from the brush boarder membrane vesicles
      (BBMV) of the midgut epithelium, were characterized.

PMID- 12044498
TI  - Analysis of the sequence and expression of a second putative acetylcholinesterase
      cDNA from organophosphate-susceptible and organophosphate-resistant cattle ticks.
AB  - The cattle tick, Boophilus microplus, is a major pest of cattle in Australia,
      Central and South America, and parts of Africa and Asia. Control of ticks with
      organophosphates (OPs) and carbamates, which target acetylcholinesterases (AChE),
      led to evolution of resistance to these pesticides. Alleles at the locus studied
      here, AChE2, from OP-susceptible female ticks from Australia and Mexico differed
      at 46 of 1689 nucleotide positions (20 putative amino acid differences) whereas
      alleles from three strains of OP-resistant ticks from Australia differed with the
      allele from the Australian susceptible ticks at six to 13 nucleotide positions
      (three to six putative amino acid differences). However, the role, if any, of
      these polymorphisms in the OP-resistance phenotype is unknown. Certainly none of
      the polymorphisms correspond to sites in AChE that are involved in catalysis or
      binding of acetylcholine in other organisms. Both of the AChE loci of B.
      microplus, AChE1 and AChE2, are apparently expressed in synganglia; AChE1 is also
      expressed in salivary glands and ovaries, in OP-susceptible and OP-resistant
      ticks. This seems to contradict studies of enzyme kinetics, which indicated that
      only one form of AChE was present in the synganglia, the site of the action of
      OPs, in this species of tick.

PMID- 12044499
TI  - Amino acid sequence and structure modeling of savignin, a thrombin inhibitor from
      the tick, Ornithodoros savignyi.
AB  - The full-length gene of savignin, a potent thrombin (E.C. 3.4.21.5) inhibitor
      from the tick Ornithodoros savignyi has been cloned and sequenced. Both 5' and 3'
      UTR's, a signal peptide from the translated amino acid sequence and an unusual
      poly-adenylation signal (AATACA) has been identified. The translated protein
      sequence shows high identity (63%) with ornithodorin, the thrombin inhibitor from
      the tick, Ornithodoros moubata. Molecular modeling using the structure of
      ornithodorin as reference gave a structure with an RMSD of 0.25 A for the full
      length protein, 0.11 A for the N-terminal BPTI-like domain and 0.11 A for the C
      terminal BPTI-like domain, indicating that maximum deviation occurs in the mobile
      bridge (0.18 A) between the two domains. Docking of savignin to thrombin shows
      that the interaction is similar to the ornithodorin-thrombin complex. The N
      terminal amino acid residues of savignin bind inside the active site cleft, while
      the C-terminal domain of savignin has a net negative electrostatic potential and
      interacts with the basic fibrinogen recognition exosite of thrombin through
      hydrogen bonds and hydrophobic interactions. These results correlate with kinetic
      data obtained, which showed that savignin is a competitive, slow, tight-binding
      inhibitor that requires thrombin's fibrinogen-binding exo-site for optimal
      inhibition.

PMID- 12044501
TI  - Current treatment of follicular non-Hodgkin's lymphoma.
AB  - 56200 new cases of NHL are expected to be diagnosed in the United States (US) per
      year. For reasons that are not fully understood, the number of new cases per year
      has nearly doubled in the past three decades. Most patients with follicular
      lymphoma are over 50 years of age and present with widespread disease at
      diagnosis. Nodal involvement is very common, often accompanied by splenic and
      bone marrow disease. Despite the advanced stage, the median survival ranges from
      8 to 12 years. The vast majority of patients with advanced stage follicular
      lymphoma are not cured using the current therapeutic options. The rate of relapse
      is fairly consistent over time, even in patients who have achieved complete
      responses (CRs) to treatment. Therapeutic options in follicular NHL include
      watchful waiting, oral alkylating agents, purine nucleoside analogues,
      combination chemotherapy, interferon and monoclonal antibodies. Radiolabelled
      monoclonal antibodies, autologous or allogeneic bone marrow or peripheral stem
      cell transplantation are under current clinical evaluation. The approval of
      rituximab, an unconjugated chimeric antibody against the CD20 antigen for the
      treatment of relapsed follicular B-cell NHL marked a milestone in the development
      of antibody treatment. In addition, newer approaches like radioimmunoconjugates
      with myeloablative activity induced response rates of 80-100% in heavily
      pretreated patients. Various clinical trials combining monoclonal antibodies with
      conventional therapies are currently ongoing to determine whether these new
      biological agents will alter the natural history of follicular lymphoma.

PMID- 12044500
TI  - Editorial comment on 'Serum markers in breast cancer management'.

PMID- 12044502
TI  - Treatment outcome studies. pitfalls in current methods and practice.
AB  - The objective of a treatment outcome study is to investigate the heterogeneity in
      outcome between patients according to factors other than treatment, such as
      country, institution or physician. Results of treatment outcome studies have
      already been extensively presented in the medical literature. However, no clear
      methodology has emerged to perform treatment outcome studies and various methods
      have been used. This paper reviews the different types of questions addressed in
      treatment outcome studies, the different methodologies and the different
      endpoints used. Statistical techniques are mainly descriptive including tables,
      estimates of survival curves, but regression models have also been used. Most of
      the studies use registry data, while only a few use discharge data or data
      available from clinical trials.

PMID- 12044503
TI  - Prognostic role of serum CA15.3 in 362 node-negative breast cancers. An old
      player for a new game.
AB  - The aims of the present investigation were to evaluate the association between
      serum CA15.3 levels and other biological and clinical variables and its
      prognostic role in patients with node-negative breast cancer. We evaluated 362
      patients operated upon primary breast cancer from 1982 to 1992 (median follow-up
      69 months). Serum CA15.3 was measured by an immunoradiometric assay. The
      association between variables was investigated by a Principal Component Analysis
      (PCA) and the prognostic role of CA15.3 on relapse-free survival (RFS) was
      investigated by Cox regression models adjusting for age, oestrogen receptor (ER),
      tumour stage, and ER x age interaction, with both the likelihood ratio test and
      Harrell's c statistic. The prognostic contribution of CA 15.3 was highly
      significant. Log relative hazard of relapse was constant until approximately 10
      (U/ml) of CA15.3 and increased thereafter with increasing marker levels. CA15.3
      showed a significant contribution using as a cut-off point a value of 31 U/ml.
      However, the contribution to the model of the marker as a continuous variable is
      much greater. From these findings, we can conclude that: (i) CA15.3 is a
      prognostic marker in node-negative breast cancer; (ii) its relationship with
      prognosis is continuous, with the risk of relapse increasing progressively from
      approximately 10 U/ml.

PMID- 12044504
TI  - Ca 15-3 in the follow-up of localised breast cancer: a prospective study.
AB  - Altogether, 243 female breast cancer patients with localised disease diagnosed
      between 1991 and 1995 in the Tampere University Hospital area were followed
      prospectively after primary treatment until the first relapse. In the follow-up
      period, the serum tumour marker Ca 15-3 was analysed every 6 months to ascertain
      the validity of this marker in detecting the first relapse. The sensitivity and
      specificity of the test were analysed in different metastatic situations. During
      the 5 years of follow-up, 59 (24%) relapses were discovered. Ca 15-3 was elevated
      in 21/59 (36%) of the relapsed cases at least once. The 59 patients were
      subjected to 199 tests, of which 25 (13%) were positive. Among the 184 patients
      without recurrence, there were 6 (3%) with a positive Ca 15-3 level. The test
      failed to detect locoregional relapse or contralateral breast cancer. It was
      elevated in approximately half of bone-only metastases and in all of the liver
      only metastases. In the pulmonary-only recurrences, the marker value was not
      elevated. We conclude that the Ca 15-3 tumour marker test is specific, but not
      sensitive enough to indicate the first relapse earlier than other methods. The
      positive predictive value especially remained poor in patients with a relatively
      good prognosis. Our results confirm that the test is not suitable alone for
      breast cancer follow-up.

PMID- 12044506
TI  - Hormone receptor status in primary breast cancer--time for a consensus?
AB  - In a previous study, we demonstrated wide variability in the access to oestrogen
      receptor (ER) measurement, patient selection, choice of technique and the cut-off
      point for positivity. The aim of this study was to update information on the
      current use of ER and progesterone receptor (PR) measurement in the United
      Kingdom (UK). Questionnaires, asking about availability, use and technique of ER
      and PR measurement, were returned from 170 (74%) units in the UK. Where ER
      positivity was determined using the percentage of cells staining positive (33%),
      the absolute cut-off point for positivity varied widely from 5 to 80% of cells.
      Of the 170 responding units, 107 (63%) felt that PR measurement was important.
      This study confirms considerable variability in both the technique of ER
      measurement and the absolute cut-off point for positivity (5-80%). It is
      essential that a consensus be reached regarding the choice of technique, as well
      as the threshold for positivity.

PMID- 12044505
TI  - Weekly chemotherapy with carboplatin, docetaxel and irinotecan in advanced non
      small-cell-lung cancer: a phase II study.
AB  - The aim of this study was to evaluate the efficacy and tolerability of
      carboplatin, docetaxel plus irinotecan given weekly to patients with locally
      advanced or metastatic non-small cell lung cancer (NSCLC). 50 patients with
      previously untreated NSCLC (stage IIIB 10; stage IV 40; 44% squamous cell
      carcinoma; median Eastern Cooperative Oncology Group (ECOG) status 1) received
      intravenous (i.v.) carboplatin area under the curve (AUC) 2, docetaxel 20 mg/m(2)
      and irinotecan 60 mg/m(2) on days 1, 8 and 15, repeated every 5 weeks.
      Prophylactic granulocyte colony-stimulating factor (G-CSF) 150 ug/m(2) was given
      from days 3 to 6 and 10 to 13. Response was evaluated every two cycles. Four
      complete responses (8%) and 24 (48%) partial responses were observed, giving an
      overall intent-to-treat response rate of 56%. 8 patients (16%) achieved stable
      disease and 14 (28%) progressed. The median time to progression (TTP) was 9.6
      months (range 2.5-21.8 months), median survival was 14.8 months (range 0.3-27+
      months) and actuarial 1-year survival time was 55%. Grade 3/4 anaemia and
      thrombocytopenia occurred in 18 and 22% of patients, respectively; 13 patients
      (26%) developed grade 3/4 neutropenia and 7 (14%) had neutropenic fever that
      required hospitalisation, but was successfully treated with antibiotics and G-CSF
      support. One patient developed a severe allergy during docetaxel administration
      and was withdrawn. Other grade 3/4 adverse events included diarrhoea (n=14; 3
      required hospitalisation), nausea/vomiting (n=9), neurotoxicity (n=5) and fatigue
      (n=5). 6 patients required a dose reduction. This combination of i.v. carboplatin
      AUC 2, docetaxel 20 mg/m(2) and irinotecan 60 mg/m(2) given weekly is highly
      effective in the treatment of chemotherapy-naive advanced NSCLC. Toxicity was
      moderate, but manageable.

PMID- 12044507
TI  - Raltitrexed in the treatment of elderly patients with advanced colorectal cancer:
      an active and low toxicity regimen.
AB  - In spite of the high prevalence of advanced colorectal cancer in the elderly, we
      have little data on the efficacy and toxicity of chemotherapy in this age group.
      Raltitrexed is a thymidylate synthetase inhibitor with known activity in the
      treatment of advanced colorectal cancer. The objective of this study was to
      analyse the efficacy and tolerance of raltitrexed in elderly patients with
      advanced colorectal cancer. 92 patients diagnosed with advanced colorectal cancer
      aged >or=70 years were entered into the study. Raltitrexed was given at a dose of
      3 mg/m(2) once every 3 weeks for a minimum of three cycles. A total of 511 cycles
      were given with a median of five cycles per patient. 20 out of the 90 patients
      evaluable for response achieved a partial response (PR) (22%, 95% Confidence
      Interval (CI): 17-36%), 43 (48%) remained stable and 27 showed progression (30%).
      The mean duration of response was 24 weeks and the progression-free interval was
      15 weeks. The overall median survival was 41 weeks. 31 patients (39%, 95% CI: 28
      50%) experienced a clinical benefit (improvement of the performance status
      without a worsening of symptoms or relief of symptoms without a worsening of the
      performance status). The main toxicities were gastrointestinal and
      haematological. 12 patients (13%) developed grade 3-4 side-effects: 7 had
      nausea/vomiting (8%), 6 a transaminase increase (7%), 4 asthenia (4%), 3
      diarrhoea (3%), 2 neutropenia (2%), 2 anaemia (2%) and 1 thrombocytopenia (1%).
      Three toxic deaths occurred (3%). The group of patients with a creatinine
      clearance <or=1.08 ml/s was found to have a higher risk of developing grade 3-4
      toxicity compared with those with adequate renal function (8/18 versus 4/72;
      P<0.001). In conclusion, raltitrexed is an active, convenient and low toxicity
      treatment for the elderly with advanced colorectal cancer. However, it must be
      used cautiously in elderly patients with a creatinine clearance <or=1.08 ml/s
      since they are at a higher risk of suffering grade 3-4 toxicity.

PMID- 12044508
TI  - Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer.
AB  - A feasibility study was performed to assess the toxicity and efficacy of a
      combination of gemcitabine-radiotherapy in patients with locally advanced
      pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable
      LAPC were included; the median age of the patients was 63 years (range 39-74
      years). The performance status ranged from 0 to 2. Gemcitabine was administered
      at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy,
      on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued
      thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the
      response and toxicity. All patients were evaluable for toxicity and response. The
      objective response rate was 29.2% (1 complete remission+6 partial remissions); 12
      patients had stable disease. However, 2 of the radiological partial remissions
      were shown to be complete remissions by pathology assessment. Median duration of
      response was 3 months (range 1-35+months). Median time to progression was 7
      months (range 2-37+months). Median survival was 10 months (range 3-37+months).
      Dose reduction or omission of gemcitabine was necessary in 10 patients. Non
      haematological toxicity consisted of 87.5% nausea and vomiting grade I-II,
      diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with
      bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months
      after treatment. Anaemia grade III-IV was observed in 8.3% of the patients.
      Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in
      16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour
      cells were found. In addition, in the patient who suddenly died of a fistula
      between the duodenum and aorta, no viable tumour cells were detectable at
      autopsy. Although the toxicity of this treatment was occasionally severe, the
      response and survival are encouraging and warrant further studies of this
      combination.

PMID- 12044509
TI  - Does the histological subtype of high-grade central osteosarcoma influence the
      response to treatment with chemotherapy and does it affect overall survival? A
      study on 570 patients of two consecutive trials of the European Osteosarcoma
      Intergroup.
AB  - Large randomised trials are mandatory when one wants to examine the effects of
      different aspects (such as the treatment modality) of a pathological condition on
      the overall outcome. This is especially true when studying a disease in which
      there is a multifactorial influence on progression and outcome such as
      osteosarcoma. Data on 570 patients with biopsy-proven primary central
      osteosarcoma of an extremity included in two consecutive studies of the European
      Osteosarcoma Intergroup (EOI) were analysed in order to evaluate if the
      histological subtype of the biopsy specimen correlated with the subtype of
      osteosarcoma represented in the resected specimen, if there was a relationship
      between the histological subtype and overall survival and if there was a
      relationship between the histological subtype and histological response to
      chemotherapy. High-grade osteosarcoma, as defined by established criteria, was
      subtyped as either conventional, chondroblastic, teleangiectatic, small cell,
      fibroblastic, osteoclast rich, anaplastic and sclerotic/osteoblastic well
      differentiated. A panel of experienced pathologists with a special interest in
      bone pathology was appointed to review the histological diagnosis and to assess
      the tumour response to chemotherapy on the resected specimen of each patient
      entered into the trials. Subtyping on the biopsy specimen proved to be highly
      representative for the subtype of the whole tumour. In 102 patients for which
      subtyping was performed on the biopsy and the resected specimens, there were only
      two discrepancies. Of the 568 patients for whom subtype was available, 404 (71%)
      were of the conventional type, 54 (10%) were chondroblastic, 53 (9%) had
      fibroblastic tumours and the remainder consisted of rare subtypes. A good
      response to preoperative chemotherapy was defined as 90% or more necrosis. The
      proportion of patients responding well to chemotherapy differed significantly
      between subtypes (Chi-square test statistics=11.44, P=0.01 on 3 degrees of
      freedom (d.f.)). In comparison with the conventional subtype, there was a higher
      proportion of good responders in the fibroblastic group and a lower proportion of
      good responders in the chondroblastic group. Good responders had a significantly
      better survival than patients who responded poorly to the pre-operative
      chemotherapy (logrank statistic=25.20, P<0.01 on 1 df). Survival did not differ
      significantly according to subtype (logrank statistic=2.72, P=0.44 on 3 df),
      although there was a suggestion that patients with chondroblastic tumours
      experienced a better long-term survival. This large set of prospectively
      collected data provides important information on the relationship between
      pathological subtype, histological response and survival. Histological response
      has a known prognostic effect on survival, and we have shown that the rates of
      response differ by subtype. There is some evidence from this study that the
      specific histological subtypes, i.e. the chondroblastic subtype, experience
      better survival. However, despite this large multi-institutional study, we have
      insufficient numbers of non-conventional tumours to examine this unambiguously
      for these subsets.

PMID- 12044510
TI  - Childhood cancer patients at school.
AB  - The aim of this study was to assess the school-related problems of childhood
      cancer patients. A cross-sectional questionnaire study for school-aged children
      with extracranial malignancies, in the area of Turku University Hospital serving
      around 1000000 people. Siblings, healthy pupils and teachers were studied as
      controls. 43 patients responded. None of the patients or controls was placed in
      special educational programmes. However, 30.8% of the patients, 15.7% of the
      controls and 3.7% of the siblings had required extra tutoring. The patients'
      results differed statistically from both the siblings' (P=0.022) and the
      controls' (P=0.041) results. The school marks in mathematics (P=0.05) and in
      foreign languages (P=0.06) tended to be worse for the patients than for the
      healthy controls. Bullying was reported by 31.7% of the patients, 10.9% of
      controls (P=0.0012) and 8.3% of the siblings (P=0.056). The biggest problem faced
      by the cancer patients was bullying-the patients reported approximately 3 times
      as much bullying as the healthy children did. It seems that there are still
      several aspects which need to be reconsidered when these children return to
      school or start their school-life as survivors of childhood cancer. Some
      proposals are presented.

PMID- 12044511
TI  - The quality of survival after childhood cancer.

PMID- 12044513
TI  - Second primary cancers in laryngeal cancer patients in Slovenia, 1961-1996.
AB  - We analysed the incidence of second primary cancers (SPC) in male laryngeal
      cancer patients in Slovenia and their survival for the period of 1961-1996. Data
      were taken from the population-based Cancer Registry of Slovenia. The person
      years approach was used and the risk for SPC was expressed as a standardised
      incidence ratio (SIR). Survival analysis was carried out using the Kaplan-Meier
      method. Of 2275 male patients, 369 developed SPC (16.2%, total SIR 2.83), most
      commonly in the head and neck region (SIR 6.07-15.97), lung (SIR 4.15),
      oesophagus (SIR 4.66), and bladder (SIR 3.0), which points to an important role
      of common risk factors of smoking and alcohol. SPC were diagnosed in significant
      excess up to 20 years after the diagnosis of laryngeal cancer. The median
      survival time from the diagnosis of laryngeal cancer was 3.25 years for patients
      without a SPC and 6.47 years for patients who developed a SPC. However, the
      median survival time from the diagnosis of a SPC was only 0.84 years. Patients
      with laryngeal cancer in Slovenia have a higher risk of developing a SPC than was
      reported in similar studies in Europe and the USA. This high risk is partly
      responsible for their relatively poor survival.

PMID- 12044514
TI  - Regulation of B16F1 melanoma cell metastasis by inducible functions of the
      hepatic microvasculature.
AB  - We have previously shown that circulating intravascular cells generally arrest by
      mechanical restriction in the hepatic sinusoids, causing rapid release of nitric
      oxide (NO) which is cytotoxic to these cells and inhibits their growth into
      metastatic tumours. Here, we present evidence that these NO-dependent cytotoxic
      mechanisms are susceptible to upregulation by lipopolysaccharide (LPS). Five x
      10(5) fluorescently labelled melanoma cells were injected into the mesenteric
      vein of C57BL/6 mice to effect their localisation in the hepatic
      microvasculature. Test mice were then given 1 mg/kg LPS intraperitoneally (i.p.)
      to activate the microvascular cells. By electron paramagnetic resonance (EPR)
      spectroscopy, the expression of NO in the liver was significantly increased by 8
      h in the LPS-treated mice. The non-selective NO synthase inhibitor L-NAME
      inhibited the induction of NO by LPS, while its inactive enantiomer D-NAME had no
      significant effect. Using immunohistochemistry (IHC), iNOS-positive microvascular
      cells were detected in the terminal portal venule (TPV) region of the liver 8 h
      after LPS stimulation. LPS treatment also increased the retention of melanoma
      cells in the liver between 8 and 24 h, especially in the TPV region. Eight hours
      after cell injection, local expression of VCAM-1 and ICAM-1 was detected by
      double-label immunohistochemistry at the sites of tumour cell arrest. Expression
      of these adhesion molecules was enhanced in mice treated with LPS. Using flow
      cytometry, 98% of the B16F1 melanoma cells expressed VLA-4, the counter receptor
      of VCAM-1, and approximately 1.5% expressed LFA-1, the counter receptor of ICAM
      1. LPS did not significantly alter the expression of either counter receptor on
      melanoma cells in vitro or in vivo. By DNA end-labelling, the rates of melanoma
      cell apoptosis were significantly increased from 8 to 24 h in the TPV region (but
      not in the sinusoids) of LPS-treated mice. Fourteen days after tumour cell
      injection, the LPS-treated mice had a significantly smaller hepatic metastatic
      tumour burden than the control mice. These data suggest that LPS can inhibit the
      metastasis of melanoma cells in the liver by inducing the expression of NO and
      adhesion molecules by the hepatic endothelium. The induction of iNOS and the
      inducible cytotoxic effect of LPS appear to be primarily located within the TPV
      region of the liver acinus.

PMID- 12044515
TI  - Enhancement of the antitumour activity of 5-fluorouracil (5-FU) by inhibiting
      dihydropyrimidine dehydrogenase activity (DPD) using 5-chloro-2,4
      dihydroxypyridine (CDHP) in human tumour cells.
AB  - The purpose of this study was to evaluate the use of 5-chloro-2,4
      dihydroxypyridine (CDHP), a potent inhibitor of dihydropyrimidine dehydrogenase
      (DPD), to enhance the antitumour activity of the fluoropyrimidines. In an in
      vitro study, CDHP did not influence cell proliferation by itself. However, CDHP
      did inhibit 5-fluorouracil (5-FU) degradation and enhanced 5-FU cytotoxicity in a
      concentration-dependent manner in two human tumour cell lines (MIAPaCa-2 and
      HuTu80) with relatively high basal DPD activity. CDHP exhibited a maximum effect
      at a molar ratio (CDHP:5-FU) of more than 0.2. However, CDHP did not have any
      effect on 5-FU cytotoxicity in the CAL27 tumour cell line, which has a relatively
      low basal DPD activity, even at concentrations where the DPD activity is almost
      completely inhibited. In an in vivo study, the maximal tolerable doses (MTD) of
      tegafur (FT) and a combination of FT and CDHP at a molar ratio of 1:0.4 (FT/CDHP)
      for nude mice were determined by oral administration for 14 consecutive days.
      After a single oral administration of either FT or FT/CDHP at the MTD, the 5-FU
      serum concentration-time profiles were almost the same for both treatment
      strategies. When nude mice bearing subcutaneous (s.c.) MIAPaCa-2 cells were
      treated with either FT or FT/CDHP at the MTD, the FT/CDHP treatment showed a
      significantly higher antitumour effect than the FT treatment (tumour growth
      inhibition: FT/CDHP, 51+/-12%; FT, 21+/-25%; P<0.05). However, the host-body
      weight suppression induced by FT/CDHP and FT was equivalent. These findings
      suggest that the combination of fluoropyrimidine and CDHP for the treatment of
      tumours with a high basal DPD elicits a greater antitumour effect than treatment
      with fluoropyrimidines alone and we suggest that CDHP inhibits the degradation of
      5-FU in the tumour.

PMID- 12044516
TI  - Therapy of rat tracheal carcinoma IC-12 in SCID mice: vascular targeting with
      [213Bi]-MAb TES-23.
AB  - In previous work, we have demonstrated that vascular targeting of [213Bi], an
      alpha-emitter, to lung blood vessels could efficiently destroy tumour colonies
      growing in the lung. In order to expand this approach to treatment of tumours
      growing in other sites, we employed the monoclonal antibody (MAb) TES-23, which
      reacts with CD44H, preferentially expressed on new blood vessels in tumours.
      Biodistribution studies of N-succinimidyl [125I] 3-iodobenzoate (SIB)
      radiolabelled MAb TES-23 in ICR-severe combined immunodeficient (SCID) mice
      bearing subcutaneous (s.c.) and intramuscular (i.m.) IC-12 tumours, demonstrated
      efficient tumour uptake. At 24 h, accumulation in small tumours was 45%ID/g for
      s.c. tumours, and 58%ID/g for i.m. tumours and in large tumours it was 25%ID/g
      for s.c. tumours and 17%ID/g for i.m. tumours. Micro-autoradiography data
      confirmed that radiolabel accumulated in or near tumour blood vessels. Normal
      tissues had very low levels of radioactivity. Treatment of mice bearing small IC
      12 tumours with [213Bi] MAb TES-23 retarded tumour growth relative to animals
      treated with cold MAb TES-23. Biodistribution and therapy experiments were also
      performed in BALB/c mice bearing both s.c. and i.m. syngeneic, lung carcinoma
      (line 498) tumours. [I(125)] SIB MAb TES-23 accumulated efficiently in both s.c.
      and i.m. tumours (14%ID/g and 15%ID/g, respectively, at 4 h); however, no
      therapeutic effect of [213Bi] MAb TES-23 treatment could be demonstrated in this
      model system. The data demonstrate that the timing of vascularisation of the
      tumours and the delivery kinetics of MAb relative to the half-life of the
      therapeutic radionuclide are critical for effective therapy.

PMID- 12044517
TI  - Trends in breast-conserving surgery in the Southeast Netherlands: comments on
      article by Ernst and colleagues. Eur J Cancer 2001, 37, 2435-2440.

PMID- 12044520
TI  - Regulation of organic anion transporters in a new rat model of acute and chronic
      cholangitis resembling human primary sclerosing cholangitis.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic liver
      disease of unknown etiology. Although the primary defect affects cholangiocytes,
      cholestatic injury of hepatocytes may promote further liver damage. Since down
      regulation of hepatocellular organic anion transporters is implicated in the
      molecular pathogenesis of cholestasis, expression of these transporters was
      determined in a novel rat model, which closely resembles human PSC. METHODS:
      Hepatic protein and mRNA expression of basolateral (Ntcp, Oatp1, 2 and 4) and
      canalicular (Mrp2, Bsep) organic anion transporters were analyzed 1, 4 and 12
      weeks after induction of experimental PSC by 2,4,6-trinitrobenzenesulfonic acid
      (TNBS). RESULTS: Specific down-regulation of basolateral and canalicular
      transport systems except Oatp4 and Bsep proteins occurred during the acute phase
      of inflammation. In chronic cholangitis 12 weeks after TNBS Mrp2 protein and mRNA
      remained down-regulated by 40-50% of controls (P<0.05). In addition Oatp1 protein
      was also reduced by 40+/-13% (P<0.05), whereas all other transporters returned to
      control values. CONCLUSIONS: In chronic cholangitis only canalicular Mrp2
      expression remained down-regulated. This might represent the first injury to
      hepatocytes in chronic cholangitis as an extension of liver injury from the level
      of cholangiocytes to hepatocytes in PSC.

PMID- 12044521
TI  - A highly specific isolation of rat sinusoidal endothelial cells by the
      immunomagnetic bead method using SE-1 monoclonal antibody.
AB  - BACKGROUND/AIMS: To develop a specific isolation method of hepatic sinusoidal
      endothelial cells (SEC), we applied the immunomagnetic method using a monoclonal
      antibody (SE-1) that recognizes a membranous antigen expressed only in rat SEC.
      METHODS: Cells were isolated by incubating mixed non-parenchymal cells, which
      were obtained by collagenase digestion of the liver, with SE-1-conjugated
      superparamagnetic polystyrene beads. The conventional Percoll method was also
      performed in parallel to compare with the immunomagnetic method. The isolated
      cells were cultured on glass coverslips coated with type I collagen in the
      presence of various growth factors for 6 days. RESULTS: Approximately 98% of the
      isolated cells were positive for SE-1 and the contamination of Kupffer cells or
      stellate cells was less than 1%. The purity was significantly better than that
      obtained by the Percoll method. The cultured cells showed typical SEC features,
      such as sieve plates and uptake of acetylated low-density lipoprotein. Although
      the cells continuously underwent apoptotic cell death after 2 days, they started
      robust cell growth after 3 days and were well maintained during the culture
      period. CONCLUSIONS: Our simple and specific isolation method enables us to
      culture SEC with high purity and should be useful for the biological analysis of
      SEC.

PMID- 12044522
TI  - Phenotypic analysis of circulating and intrahepatic dendritic cell subsets in
      patients with chronic liver diseases.
AB  - BACKGROUND/AIMS: Dendritic cells (DCs) are the most potent professional antigen
      presenting cells. Although two subsets of circulating DCs, lineage(
      )CD11c(+)CD4(low) (CD11c(+)DCs) and lineage (-)CD11c(-)CD4(+)CD123(+)
      (CD123(+)DCs) are identified in humans, the role of each DC subset in the
      immunopathogenesis of liver diseases is unknown. METHODS: We examined the numbers
      and activation status of each DC subset in the circulation and in the inflamed
      livers in patients with chronic liver diseases by flow cytometry and
      immunohistochemistry. RESULTS: The numbers of circulating CD11c(+)DCs were
      inversely correlated with serum alanine aminotransferase (ALT) levels in patients
      with chronic viral hepatitis, and that the expression of costimulatory molecules
      on circulating CD11c(+)DCs in patients with chronic viral hepatitis was
      significantly up-regulated in patients with high serum levels of ALT. Both DCs
      are also identified in the livers by flow cytometry, and the expression of
      costimulatory molecule CD40 on those DCs was significantly higher in liver DCs
      than that in circulating DCs. Moreover, the ratios of CD11c(+)DCs/CD123(+)DCs
      were higher in liver DCs (mean+/-SD, 7.2+/-6.0) than those of circulating DCs
      (4.0+/-4.6). Immunohistochemically, CD11c(+) or CD123(+) cells and CD83(+)
      activated DCs were observed mostly in portal areas with mononuclear cell
      infiltration in various liver diseases. These overall data suggest that DCs,
      especially CD11c(+)DCs, could be associated with the necroinflammatory response
      in the liver of chronic viral liver diseases. CONCLUSIONS: DCs, especially
      CD11c(+)DCs, may be involved in the immunopathogenesis of chronic liver diseases.

PMID- 12044523
TI  - Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF
      kappaB-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis.
AB  - BACKGROUND/AIMS: In acute liver failure, hepatocytes are exposed to various
      cytokines that activate both cell survival and apoptotic pathways. NF-kappaB is a
      central transcription factor in these responses. Recent studies indicate that
      blocking NF-kappaB causes apoptosis, indicating the existence of NF-kappaB
      regulated anti-apoptotic genes. In the present study the relationship between NF
      kappaB activation and apoptosis has been investigated in hepatocytes. METHODS:
      Primary rat hepatocytes were exposed to a cytokine mixture of tumor necrosis
      factor alpha, interleukin-1beta, interferon-gamma and lipopolysaccharide.
      Modulation of signalling pathways was performed by using dominant negative
      adenoviral constructs. Apoptosis and NF-kappaB activation were determined by
      caspase-3 activity, Hoechst staining and electrophoretic mobility shift assay,
      respectively. Furthermore, expression and regulation of apoptosis-related genes
      were investigated. RESULTS: (1) Inhibition of NF-kappaB activation results in
      apoptosis. (2) Inhibitor of apoptosis protein (IAP) family members, inhibitor of
      apoptosis protein1 (cIAP1), and X-chromosome-linked IAP, are expressed in rat
      hepatocytes. cIAP2 is induced by cytokines in an NF-kappaB-dependent manner and
      overexpression of cIAP2 inhibits apoptosis. (3) The anti-apoptotic Bcl-2 family
      member A1/Bfl-1 and the pro-apoptotic members Bak and Bid are induced by
      cytokines and NF-kappaB-dependent. (4) Nitric oxide inhibits caspase-3 activity
      in hepatocytes. CONCLUSIONS: In inflammatory conditions, hepatocyte survival is
      dependent on NF-kappaB activation and cIAP2 contributes significantly to this
      protection.

PMID- 12044524
TI  - Regulation of the growth hormone receptor/binding protein, insulin-like growth
      factor ternary complex system in human cirrhosis.
AB  - BACKGROUND/AIMS: The liver is the central organ of the endocrine growth
      hormone/insulin-like growth factor I (GH/IGF-I) axis and cirrhosis effects a
      state of acquired GH resistance. Low IGF-I levels are associated with adverse
      clinical outcomes in cirrhotic patients and may be pathogenic to the
      complications of cirrhosis. We examined the impact of cirrhosis on hepatic mRNA
      and serum protein levels for the GH receptor (GHR)/binding protein (GHBP), IGF-I,
      IGF binding protein (IGFBP)-3 and the acid-labile subunit (ALS). METHODS: Fifty
      patients with cirrhosis were studied and liver tissue was obtained from 18. Gene
      expression was assessed by Northern analysis and serum protein levels by
      immunoassay. RESULTS: In cirrhotic liver GHR mRNA and GH binding to microsomal
      membranes were decreased by 61 and 56%, respectively. Serum GHBP levels were
      decreased only in severe disease, not correlating with GHR mRNA or GH binding.
      Hepatic IGF-I and ALS mRNA were significantly decreased by 84 and 68%,
      respectively, in parallel with serum protein, suggesting transcriptional
      regulation. Hepatic IGFBP-3 mRNA was unchanged but low serum IGFBP-3 suggested
      post-transcriptional regulation. CONCLUSIONS: The decreased mRNA and serum levels
      for the GH-dependent, hepatocyte produced proteins IGF-I and ALS confirm the
      importance of GH receptor loss to the GH resistance of cirrhosis.

PMID- 12044525
TI  - Altered response to inflammatory cytokines in hepatic energy metabolism in
      inducible nitric oxide synthase knockout mice.
AB  - BACKGROUND/AIMS: Production of nitric oxide (NO) in the liver is believed to be a
      critical factor for carbohydrate and energy metabolism in endotoxin shock. The
      present study focuses on the involvement of NO produced by inducible nitric oxide
      synthase (iNOS) in glycogen synthesis and energy metabolism stimulated by
      insulin. METHODS: Primary hepatocytes prepared from wild-type and iNOS knockout
      (iNOS(-/-)) mice were employed. RESULTS: Incubation of wild-type hepatocytes with
      a combination of cytokines (interleukin-1beta, tumor necrosis factor-alpha and
      interferon-gamma) and lipopolysaccharide (cytokines/LPS) inhibited insulin
      stimulated glycogen synthesis and adenosine triphosphate (ATP) increase, and
      decreased the ketone body ratio (KBR) at 8-12 h, concomitant with expression of
      iNOS protein and NO production. While the glycogen synthesis was suppressed by
      cytokines/LPS, reduction of the ATP increase and a decrease in KBR by
      cytokines/LPS were not observed in iNOS(-/-) hepatocytes. Further, N(G)
      monomethyl-L-arginine, a NOS inhibitor, reversed the inhibition of ATP increase
      and decrease in KBR by cytokines/LPS, but not the inhibition of glycogen
      synthesis. Conversely, addition of S-nitroso-N-acetylpenicillamine, a NO donor,
      inhibited the insulin-stimulated ATP increase synthesis in iNOS(-/-) hepatocytes,
      but not the insulin-stimulated glycogen synthesis. CONCLUSIONS: These results
      demonstrate that NO mediates the suppression of insulin-stimulated energy
      metabolism, but not glycogen synthesis, in cytokines/LPS-treated hepatocytes.

PMID- 12044526
TI  - Antithrombin III prevents concanavalin A-induced liver injury through inhibition
      of macrophage inflammatory protein-2 release and production of prostacyclin in
      mice.
AB  - BACKGROUND/AIMS: Recently, we have reported that macrophage inflammatory protein
      2 (MIP-2) plays a pivotal role in concanavalin A (Con A)-induced liver injury. In
      this study, we investigated the effect of antithrombin III (AT-III) on liver
      damage, and production of MIP-2 and prostacyclin in this model. METHODS: Liver
      injury was induced by intravenous injection of Con A (15 mg/kg) and AT-III was
      administered (50, 250 and 500 units/kg, iv) 30 mm before Con A injection. Plasma
      levels of alanine aminotransferase (ALT), MIP-2 and 6-keto-prostaglandin F1alpha
      (6k-PG-F1alpha), stable metabolite of prostaglandin I(2) (prostacyclin), were
      determined. RESULTS: The elevated plasma ALT levels 8, 16, 24 h after Con A
      injection were inhibited by AT-III pretreatment. The elevated plasma MIP-2 levels
      were significantly inhibited by AT-III pretreatment compared with vehicle
      treatment. The inhibitory effect of AT-III on plasma ALT and MIP-2 in Con A
      induced liver injury was attenuated by indomethacin (5 mg/kg, ip). Plasma
      concentration of 6k-PG-F1alpha at 2 h after AT-III injection was significantly
      elevated compared with baseline and vehicle pretreatment. CONCLUSIONS: These
      findings suggest that AT-III prevents Con A-induced liver injury through an
      inhibition of MIP-2 release and a production of prostacyclin.

PMID- 12044527
TI  - Microwave coagulation therapy accelerates growth of cancer in rat liver.
AB  - BACKGROUND/AIMS: Although microwave coagulation therapy (MCT) has been performed
      for liver cancer, there has been no report examining the influence of this
      therapy on the growth of possible remnant cancer. METHODS: A solid cube of AH-130
      cells (ascites hepatoma cell line) was implanted into the left lateral lobe of
      the rat liver. Five days later, MCT was applied to the middle liver lobe of these
      rats. Tumor growth and cytokine levels in plasma and the liver were compared
      between rats that underwent MCT and rats that did not. RESULTS: The mean tumor
      weight in the MCT group (222.6+/-51.5 mg, mean+/-SD) was significantly greater
      than that in the control group (126.7+/-19.7 mg, P<0.01) at postoperative day
      (POD) 5. Immunohistochemistry for anti-proliferating cell nuclear antigen showed
      the labeling index in the MCT group (90.4%) to be higher than that in the control
      group (76.7%, P<0.01). Liver basic fibroblast growth factor and transforming
      growth factor-beta 1 levels in the MCT group on POD 3 were significantly higher
      than levels in the control group. CONCLUSIONS: The present study suggests the
      clinically important finding that MCT accelerates the growth of small residual
      tumors in the liver.

PMID- 12044528
TI  - Gene amplification and mRNA and protein overexpression of c-erbB-2 (HER-2/neu) in
      human intrahepatic cholangiocarcinoma as detected by fluorescence in situ
      hybridization, in situ hybridization, and immunohistochemistry.
AB  - BACKGROUND/AIMS: The human proto-oncogene c-erbB-2 (also called HER-2/neu) is
      located on chromosome 17q21-22. There have been no studies on gene amplification
      or mRNA expression of c-erbB-2 in human intrahepatic cholangiocarcinoma (CC)
      hitherto. METHODS: We investigated c-erbB-2 gene amplification by fluorescence in
      situ hybridization (FISH), c-erbB2 mRNA expression by ISH, and c-erbB-2 protein
      expression by immunohistochemistry in 22 archival cases of CC. RESULTS: FISH
      revealed that c-erbB-2 gene signals were increased in CC. ISH showed that c-erbB
      2 mRNA signals were located in the nuclei and cytoplasms of cancer cells and were
      increased in cancer cells compared with non-cancerous bile ducts where no signals
      were present. Immunohistochemistry showed that the c-erbB-2 protein was expressed
      in the cell membrane of cancer cells, and was increased compared with non
      cancerous bile ducts where no expression was found. There was a positive
      significant correlation between c-erbB-2 mRNA and protein expression.
      Clinicopathologically, there were no correlations between the c-erbB-2 expression
      and various pathological features. CONCLUSIONS: These data suggest that c-erbB-2
      gene amplification does occur in CC, and that there is an overexpressed c-erbB-2
      protein through the enhanced mRNA expression. The c-erbB-2 gene amplification may
      be related to the oncogenesis or tumor progression of CC.

PMID- 12044529
TI  - The tumor-associated antigen, RCAS1, can be expressed in immune-mediated diseases
      as well as in carcinomas of biliary tract.
AB  - BACKGROUND/AIMS: RCAS1, which is recognized by the specific antibody 22-1-1, was
      first identified as a tumor-associated antigen in gynecological carcinomas. RCAS1
      is the ligand of a putative receptor present on lymphocytes, the expression of
      which is enhanced by lymphocyte activation. RCAS1 inhibits the growth of receptor
      bearing cells and induces apoptotic death. Here we examined RCAS1 expression in
      biliary diseases. METHODS: RCAS1 expression was immunohistochemically examined on
      tissue samples. Apoptotic death was analyzed by DNA fragmentation detection
      method. RCAS1 production by cell lines was investigated by flow cytometry, enzyme
      linked immunosorbent assay, and reverse transcription-polymerase chain reaction.
      RESULTS: All cholangiocarcinoma cell lines examined clearly expressed RCAS1 at
      both the protein and RNA level. Immunohistochemically, RCAS1 was expressed in a
      high percentage of biliary adenocarcinomas (85.9% of intrahepatic
      cholangiocarcinomas, 96.4% of extrahepatic cholangiocarcinomas and gallbladder
      carcinomas). Apoptotic tumor-infiltrating lymphocytes could be found in these
      specimens. RCAS1 expression was frequently detected also in biliary epithelial
      cells in cases of immune-mediated cholangitis (74.2% in primary biliary
      cirrhosis, 66.6% in graft-versus-host disease), although the staining pattern for
      RCAS1 was different compared with cancer cells. CONCLUSIONS: RCAS1 is highly
      expressed not only in cancer cells but also in non-tumor bile duct cells
      subjected to immune attack.

PMID- 12044530
TI  - Influence of superimposed alcoholic hepatitis on the outcome of liver
      transplantation for end-stage alcoholic liver disease.
AB  - BACKGROUND/AIMS: Alcoholic cirrhosis is a common indication for liver
      transplantation. The present study was aimed to assess the influence of
      superimposed alcoholic hepatitis on the outcome of liver transplantation in
      patients with alcoholic cirrhosis. METHODS: Survival rates of 68 patients
      transplanted for alcoholic cirrhosis were compared with those of 101 patients
      transplanted for miscellaneous causes. Within the alcoholic group, explanted
      livers were searched for data of acute alcoholic hepatitis. The survival rate of
      patients with alcoholic hepatitis superimposed on liver cirrhosis was compared to
      that of patients with liver cirrhosis alone. Clinical severity of alcoholic
      hepatitis was assessed with Maddrey's score. RESULTS: Survival was similar in
      alcoholics and patients with other causes of liver disease. Among patients
      transplanted for alcoholic cirrhosis, survival was similar in patients with
      superimposed alcoholic hepatitis (n=36) and in cases with liver cirrhosis alone
      (n=32). There was no difference in survival between patients with mild (n=26) and
      severe (n=10) alcoholic hepatitis. Seven alcoholics (10%) returned to ethanol
      consumption. Recidivism was not associated with either alcoholic hepatitis in the
      explanted liver or graft loss. CONCLUSIONS: Survival after liver transplantation
      in patients with alcoholic cirrhosis plus alcoholic hepatitis detected in the
      explanted liver is similar to that of patients transplanted for other reasons.
      Even the presence of severe alcoholic hepatitis does not worsen the outcome of
      liver transplantation for end-stage alcoholic liver disease.

PMID- 12044531
TI  - Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis
      B patients: a controlled pilot study.
AB  - BACKGROUND/AIMS: In this study, lamivudine-interferon (LAM/IFN) combination
      therapy was compared to LAM monotherapy to verify if the combination treatment
      might improve efficacy and reduce the emergence of LAM-resistant mutants.
      METHODS: Fifty patients with anti-HBe-positive chronic hepatitis B were treated
      for 12 months with LAM at 100mg/day (26 pts) or with IFN at 5MU t.i.w.+LAM
      100mg/day (24 pts). Serum ALT, HBV DNA and IgM anti-HBc were monitored during
      treatment and a 6-month follow-up. The polymerase gene was amplified by PCR and
      the region coding for YMDD motif was directly sequenced. RESULTS: All patients
      normalized ALT and cleared HBV DNA during treatment. The response was maintained
      until the end of therapy in the LAM/IFN group, while in 5/26 initial responders
      treated with LAM alone, a virological and biochemical breakthrough was observed
      after 6-10 months, and selection for YMDD variants resulted. After therapy
      discontinuation, most patients relapsed; the response rate after 6 months was 17%
      in the LAM/IFN group and 19% in the LAM group. CONCLUSIONS: In anti-HBe-positive
      chronic hepatitis B, a 12-month course of LAM/IFN combination therapy is as
      beneficial as LAM monotherapy, however, the combination regimen appeared to
      prevent or delay the emergence of YMDD variants.

PMID- 12044532
TI  - Oxidative stress in chronic hepatitis C: not just a feature of late stage
      disease.
AB  - BACKGROUND/AIMS: Chronic hepatitis C infection is a major world-wide problem,
      frequently progressing to cirrhosis, liver failure or hepatoma. The pathological
      mechanisms of disease progression are unclear but oxidant stress may play a role.
      METHODS: Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis
      and liver function were measured in blood or urine from 42 chronic hepatitis C
      patients. Fibrosis was graded histologically in a subgroup of 33 patients.
      RESULTS: The lipid peroxidation marker 8-isoprostane and the ratio of oxidized to
      reduced glutathione were significantly elevated (P<0.001, P=0.006). The
      antioxidants glutathione, selenium and vitamins A, C and E were significantly
      decreased (all P<0.001) compared to age and sex matched controls. Abnormal values
      were more marked in cirrhotics, but significant changes were also observed in the
      non-cirrhotic group. The fibrosis score correlated positively with urinary 8
      isoprostane and type III procollagen peptide and negatively with vitamin A.
      CONCLUSIONS: Oxidant stress, as reflected in blood and urine by a wide range of
      pro- and antioxidant markers, is a significant feature of hepatitis C infection.
      Although more severe in the cirrhotic group, there was clear evidence of oxidant
      stress in non-cirrhotic patients. Antioxidant therapy may therefore have a role
      in slowing disease progression to cirrhosis.

PMID- 12044533
TI  - Impact of treatment on extra hepatic manifestations in patients with chronic
      hepatitis C.
AB  - BACKGROUND/AIMS: Fatigue and other extra hepatic manifestations of hepatitis C
      have never been studied prospectively in a large cohort. The aim was to assess
      the prevalence of these symptoms prior to any treatment, and on prolonged follow
      up in treated and untreated patients. METHODS: A single-center cohort of
      consecutive patients with chronic hepatitis C was investigated prior to any
      treatment. A questionnaire was completed every 6 months for 18 months of follow
      up. RESULTS: Of 1614 patients, 431 met the inclusion criteria (56% male; age 49
      years; 60% with significant fibrosis or cirrhosis; 46% with cryoglobulinemia).
      Seventy-six were untreated; of the treated patients, 83 were sustained
      responders, 47 relapsers and 225 non-responders. At baseline, fatigue and other
      extrahepatic manifestations were present in 254 (59%) and 225 (52%) patients.
      Fatigue was improved in 29 of 83 (35%) responders versus 75 of 348 (22%) patients
      with detectable hepatitis C virus (HCV)-RNA (P=0.01). The impact of virologic
      response on fatigue persisted after adjusting for age, gender, fibrosis stage,
      and depression (odds ratio: 0.34, P<0.001). A cryoglobulin was detectable in two
      of 34 (6%) responders versus 38 of 115 (33%) patients with detectable HCV-RNA
      (P<0.001). CONCLUSIONS: In hepatitis C, a sustained virologic response is
      associated with a reduction in fatigue and cryoglobulin, but fatigue frequently
      persists despite a virologic response.

PMID- 12044534
TI  - Daily or three times per week interferon alpha-2b in combination with ribavirin
      or interferon alone for the treatment of patients with chronic hepatitis C not
      responding to previous interferon alone.
AB  - BACKGROUND/AIMS: We compared the efficacy and safety of the combined therapy of
      daily interferon alpha-2b and ribavirin with those of interferon alpha-2b three
      times per week alone or in combination with ribavirin in non-responder patients
      with hepatitis C virus (HCV) infection. METHODS: A total of 376 patients were
      randomly assigned to receive interferon alpha-2b (6 MU three times per week for
      24 weeks followed by 3 MU three times per week for 24 weeks) alone (group A) or
      in combination with ribavirin for 48 weeks (group B), or daily interferon alpha
      2b (3 MU per day for 24 weeks followed by 3 MU three times per week for 24 weeks)
      and ribavirin (group C). RESULTS: After 24 weeks of therapy, HCV RNA was
      undetectable in 11.7, 24.0, and 37.8% for groups A, B, and C, respectively.
      Sustained virological response was more frequent in patients who received
      combination therapy with three times weekly interferon (20.9%) or daily
      interferon (26.0%) than in patients who received interferon alone (5.8%)
      (P<0.001). The predictive HCV parameters for sustained response were a low viral
      load on day 7 and a negative HCV RNA on week 12. CONCLUSIONS: In conclusion, in
      non-responder patients with chronic hepatitis C, virological response with daily
      interferon and ribavirin, compared to interferon monotherapy, was significantly
      improved during treatment, although sustained virological response was similar
      for both combination therapies with ribavirin and three times a week or daily
      interferon.

PMID- 12044535
TI  - Dead or alive -- NF-kappaB, the guardian which tips the balance.

PMID- 12044536
TI  - Is liver transplantation an appropriate treatment for acute alcoholic hepatitis?

PMID- 12044537
TI  - Nuclear receptor regulation of hepatic function.

PMID- 12044538
TI  - Aceruloplasminemia: new clinical, pathophysiological and therapeutic insights.
AB  - Aceruloplasminemia is an autosomal recessive disease of iron overload associated
      with mutation(s) in the ceruloplasmin gene. We report here a new case of
      aceruloplasminemia in a woman who is a compound heterozygote for two new
      mutations. Besides this novel genotypic profile, this observation provides new
      insights on: (i) iron metabolism with normal erythroid repartition, in the
      absence of serum non-transferrin-bound iron and with an increase of 59Fe plasma
      clearance; (ii) hepatic abnormalities associated with the presence of iron-free
      foci; (iii) the therapeutic management of the disease, chronic subcutaneous
      infusion of deferrioxamine being remarkably effective at reducing hepatic iron
      overload.

PMID- 12044539
TI  - Active bleeding from hepatic artery aneurysm diagnosed by magnetic resonance
      imaging.

PMID- 12044541
TI  - Role of hydroxyl radical formation in neurotoxicity as revealed by in vivo free
      radical trapping.
AB  - Reactive oxygen species have been implicated in dopaminergic toxicity caused by 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and iron. Although MPTP
      produces a parkinsonian syndrome after its conversion to 1-methyl-4
      phenylpyridine (MPP(+)) by type B monoamine oxidase (MAO-B) in the brain, the
      etiology of this disease remains obscure. MPP(+) is a highly potent dopaminbergic
      releasing agents and dopamine (DA) autoxidation catalyzed by iron and oxidative
      stress may be involved in the pathogenesis of Parkinson's disease. Neuromelanine
      synthesis from DA produce highly reactive free radicals. Although the controversy
      possible neurotoxin and/or neuroprotective roles of nitric oxide (NO) was
      discussed, NO contributes to oxidative injury to brain neurons in vivo. An
      environmental estrogen-like chemical also related to MPP(+)-induced *OH
      generation. This review describes actual mechanism of the free radicals formation
      by dialysis studies of in vivo free radical trapping in the pathogenesis of
      neurodegenerative disorders, including in the Parkinson's disease, Alzheimer
      disease and traumatic brain injuries.

PMID- 12044542
TI  - Antagonism of cyanide poisoning by dihydroxyacetone.
AB  - Dihydroxyacetone (DHA) effectively antagonized the lethal effect of cyanide in
      mice and rabbits, particularly if administered in combination with thiosulfate.
      Oral DHA (2 and 4 g/kg) given to mice 10 min before injection (i.p.) of cyanide
      increased the LD50 values of cyanide from 5.7 mg/kg to 12 and 17.6 mg/kg,
      respectively. DHA prevented cyanide-induced lethality most effectively, if given
      orally 10-15 min before injection of cyanide. A combination of pretreatment with
      oral DHA (4 g/kg) and post-treatment with sodium thiosulfate (1 g/kg) increased
      the LD50 of cyanide by a factor of 9.9. Furthermore, DHA given intravenously to
      rabbits 5 min after subcutaneous injection of cyanide increased the LD50 of
      cyanide from 6 mg/kg to more than 11 mg/kg, while thiosulfate (1 g/kg) given
      intravenously 5 min after cyanide injection increased the LD50 of cyanide only to
      8.5 mg/kg. DHA also prevented the convulsions that occurred after cyanide
      intoxication.

PMID- 12044543
TI  - Peripheral blood lymphocytes and selected serum interleukins in workers operating
      X-ray equipment.
AB  - The objective of these studies was to determine the effect of low X-ray doses on
      peripheral blood lymphocytes in the workers operating X-ray equipment. In 30
      workers and 18 persons who constituted the control group the absolute number of
      peripheral blood lymphocytes, the number of T CD4+ and T CD8+ lymphocytes, the
      ratio CD4+/CD8+ and the concentration of serum interleukins (IL-2, IL-4, IL-6)
      were tested. Subgroups with respect to sex and employment period were selected. A
      significant increase in IL-2 concentration in workers as compared to controls was
      observed and significantly decreased IL-4 level in operating X-ray equipment was
      revealed. The lowest levels of IL-4 were noted in the women subgroup. A high
      positive, statistically significant correlations between the number of
      lymphocytes and the concentration of IL-2 and the level of IL-4 were observed.
      Moreover, our studies revealed that lymphocyte number and interleukin
      concentrations in serum of X-ray operators do not depend on the assumed ranges of
      the length of employment period.

PMID- 12044545
TI  - Behavioural assessment of dimethylsulfoxide neurotoxicity in rats.
AB  - Dimethylsulfoxide (DMSO) is a solvent used to dissolve hydrophobic drugs. Recent
      studies have demonstrated that repeated administration of DMSO induces
      significant disorders of the peripheral nervous system. To address this issue, we
      have studied the behavioural effects of repeated intraperitoneal injections of
      various concentrations of DMSO (1.8-3.6-7.2%) in male Sprague-Dawley rats.
      Behavioural effects were assessed with a commonly used battery of sensory and
      motor tests. The motor tests used were actimeter and grip strength test. Sensory
      test used noxious and non-noxious mechanical (paw pressure test and von Frey
      hairs test) and thermal (plantar test and tail immersion test) stimuli. Clinical
      status of the animals was good throughout the experiment and no motor deficits
      were observed. Nevertheless, sensory assessment displayed a mechanical allodynia
      of short duration.

PMID- 12044544
TI  - DNA single strand breaks in peripheral blood lymphocytes induced by three
      nitroimidazole derivatives.
AB  - Tinidazole (TNZ), ornidazole (ONZ) and metronidazole (MTZ) are antiparasitic
      drugs (nitroimidazole derivatives) that have proven to be effective against
      Trichomonas vaginalis, Entoamoeba histolytica, Giardia lamblia and Helicobacter
      pylori. The reduction of the nitro group and the generation of short-lived
      reactive intermediates are the basis of its parasiticidal activity. This
      reduction is associated with its mutagenic activity in bacteria, although in
      mammalian cells DNA damage seems to be related to the production of reactive
      oxygen species (ROS). Using alkaline single cell electrophoresis, a significant
      increase in single strand breaks and alkali labile sites in human peripheral
      blood lymphocytes (PBL) exposed to MTZ, ONZ and TNZ at 10, 100 and 500 microg/ml
      is observed. MTZ causes less damage, especially at higher concentrations, when
      compared with TNZ, the most harmful of the drugs tested. These findings suggest
      that primary damage is induced under aerobic conditions and confirms that these
      nitroimidazoles are DNA damaging agents.

PMID- 12044546
TI  - Sister chromatid exchanges produced by imipramine and desipramine in mouse bone
      marrow cells treated in vivo.
AB  - Imipramine and desipramine are two widely used tricyclic antidepressants which
      have shown conflicting results in regard to their in vitro genotoxic evaluation.
      The aim of this investigation was to determine the capacity of these compounds to
      induce in vivo sister-chromatid exchanges (SCEs) in mouse bone marrow cells. For
      each compound, the animals were organized in five groups constituted by five
      individuals. They were intraperitoneally (ip) administered with the test
      substances as follows: a negative control group treated with 0.4 ml of distilled
      water, a positive control group administered with cyclophosphamide (70 mg/kg),
      three groups treated with imipramine (7, 20 and 60 mg/kg), and three other groups
      treated with desipramine (2, 20 and 60 mg/kg). The general procedure included the
      subcutaneous implantation to each mouse of a 5-bromodesoxyuridine tablet (45 mg),
      and 1 h later, the administration of the chemicals involved. Twenty-one hours
      after the tablet implantation, the mice received colchicine, and 3 h later their
      femoral bone marrow was obtained in KCL, fixed, and stained with the Hoechst
      Giemsa method. The results showed that both compounds were SCE inducers, starting
      from the second tested dose. The response of these compounds was dose-dependent,
      and showed that the highest tested dose increased about four times the SCE
      control level. The cellular proliferation kinetics was not affected by the
      chemicals, and the mitotic indexes were slightly diminished with the highest
      dose. These results indicate an in vivo genotoxic potential for both chemicals,
      and suggest that it is pertinent to follow their evaluation in other models.

PMID- 12044547
TI  - Effects of aluminum sulfate on erythropoiesis in rats.
AB  - The aim of this study was to investigate the effects of chronically administered
      aluminum on erythropoiesis in rats. After treatment (i.p. injections of
      Al(2)(SO(4))(3), 50 micromol/kg body weight, five times a week) for 3 months, the
      treated (Al) group showed significantly decreased hemoglobin concentration (32%)
      and hematocrit (24%) compared with the control group. Serum iron decreased
      significantly in the Al group, whereas total iron binding capacity did not
      change. Treatment did not alter the activity of hepatic, renal or cerebral delta
      ALA-D. Biochemical measurements related to 2-thiobarbituric acid-reactive
      substance (TBARS) levels from serum and hepatic, renal and cerebral homogenates
      also did not change after treatment. Hepatic concentrations of aluminum were
      higher in the Al group than in the control group. Renal and cerebral aluminum
      concentrations did not vary between groups. The present results indicate that
      exposure to aluminum sulfate promotes signs of anemia in rats as a consequence of
      alterations in iron status.

PMID- 12044548
TI  - Role of zinc ions in ricin-induced apoptosis in U937 cells.
AB  - We found that treatment of U937 cells with ZnCl(2) resulted in marked inhibition
      of ricin-induced DNA fragmentation and nuclear morphological change. Zn(2+) also
      completely inhibited the activation of caspase-3-, caspase-6-, and caspase-9-like
      proteases in ricin-treated cells, while no significant effect of Zn(2+) on these
      protease activities was observed when added directly to the lysate of ricin
      treated cells, suggesting that Zn(2+) blocks the process of the activation of
      these caspases rather than the direct inhibition of the already activated
      enzymes. Fluorescence microscopic observation with Zn(2+) specific fluorescent
      probe dansylaminoethyl-cyclen suggested that there was a substantial increase in
      probe-detectable Zn(2+) in ricin-treated cells. Since the differences in the
      total Zn(2+) contents between ricin-treated and -untreated cells as measured with
      an atomic absorption spectrophotometer were too small to explain the increase in
      probe fluorescence in ricin-treated cells, it was suggested that release of
      Zn(2+) from intracellular stores or metalloproteins may occur rather than
      enhanced uptake from the medium. The Zn(2+) probe fluorescence change was
      observed prior to the depletion of intracellular glutathione. Carbobenzoxy-Asp-1
      yl-[(2,6-dichlorobenzoyl)oxy]methane (Z-Asp-CH(2)-DCB), a caspase family protease
      inhibitor, prevented ricin-induced increase in Zn(2+) probe fluorescence. These
      results suggest that redistribution of intracellular Zn(2+) occurs during ricin
      induced apoptosis as early apoptotic event, and exogenously added Zn(2+) may
      prevent such intracellular Zn(2+) redistribution resulting in the inhibition of
      apoptosis.

PMID- 12044549
TI  - Increased production of human granulocyte-macrophage colony stimulating factor
      (hGM-CSF) by the addition of stabilizing polymer in plant suspension cultures.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that
      stimulates the production of granulocytes, macrophages, and white blood cells.
      Secretion of human GM-CSF from cell suspension cultures of genetically modified
      tobacco has been facilitated using natural mammalian leader sequences. At the mid
      exponential growth phase (day 4 after the initiation of cell suspension culture),
      GM-CSF was detected in the medium at a maximum concentration of 180 microg l(-1).
      However, the secreted GM-CSF was unstable in the medium, and rapidly degraded
      after day 5. In order to stabilize the secreted GM-CSF, three stabilizing
      polymers were tested, polyethylene glycol, polyvinylpyrrolidone and gelatin.
      Gelatin was the most effective in stabilizing the secreted GM-CSF. Following the
      addition of 5% (w/v) gelatin, the maximum GM-CSF concentration reached 783 microg
      l(-1), a 4.6-fold increase over control.

PMID- 12044550
TI  - Solid-phase genetic engineering with DNA immobilized on a gold surface.
AB  - A novel method for immobilizing large DNA fragments on a solid surface was
      developed. A mixed self-assembled monolayer of thiolated single-stranded DNA with
      inert alkanethiol was generated on a gold (Au) surface through the Au-S reaction.
      Surface-tethered DNA generated by this method was compatible with various genetic
      engineering techniques, including hybridization, polymerization, restriction
      enzyme digestion and ligation. Kinetic control of surface coverage of immobilized
      DNA was critical for optimizing genetic engineering techniques on solid-phase.
      Multi-step reaction schemes utilizing various genetic engineering techniques
      described above were employed for solid-phase gene assembly. We were able to
      immobilize DNA fragments of up to 1180 bp on a solid surface. Furthermore, we
      showed that these immobilized genes can be regenerated by PCR. The present work
      suggests that these types of assembled genes can be used to store and regenerate
      genes on solid-phase.

PMID- 12044552
TI  - Removal of surfactant solubilized polycyclic aromatic hydrocarbons by
      Phanerochaete chrysosporium in a rotating biological contactor reactor.
AB  - White rot fungi can oxidize surfactant solubilized polycyclic aromatic
      hydrocarbons (PAH). The objective of this study was to evaluate the performance
      of immobilized white rot fungus, Phanerochaete chrysosporium, to remove
      surfactant Tween 80 solubilized PAH i.e. phenanthrene, pyrene and
      benzo(alpha)pyrene in a rotating biological contactor (RBC) reactor. Results
      indicated that the immobilized P. chrysosporium in the RBC reactor system in
      continuous operation could effectively remove the three tested PAH at specific
      hydraulic loading rates and concentrations tested for each individual PAH. Batch
      operation of RBC reactor showed that the immobilized P. chrysosporium was stable
      and effective for the eight successive batch treatments of PAH in solution medium
      i.e. PAH removal was greater than 90% after 60 h, although only low levels of
      ligninolytic enzyme activity were detected. The removal of phenanthrene and
      pyrene in solution medium has been found to be a first order reaction in batch
      operation. A mass balance calculation indicated that biological oxidation was the
      main factor for removal of benzo(alpha)pyrene i.e. 95.7% in the RBC reactor.
      However, for phenanthrene and pyrene, both biological oxidation (i.e. 49 and 56%,
      respectively) and RBC disc foam adsorption (i.e. 44 and 34%, respectively) made a
      significant contribution to the removal of PAH.

PMID- 12044551
TI  - Process development and optimisation of lactic acid purification using
      electrodialysis.
AB  - Cell free sodium lactate solutions were subjected to purification based on mono-
      and bi-polar electrodialysis. Lactate concentration in the product stream
      increased to a maximum of 15% during mono-polar electrodialysis. Stack energy
      consumption averaged 0.6 kW h kg(-1) lactate transported at current efficiencies
      in the 90% range. Under optimum feed concentration (125 g l(-1)) and process
      conditions (auto-current mode with conductivity setpoints of minimum 5 and
      maximum 40 mS cm(-1)), lactate flux reached 300 g m(-2) h(-1) and water flux were
      low for mono-polar electrodialysis averaging 0.3 kg H(2)O per M lactate
      transported. Glucose in the concentrate stream solutions was reduced to < 2 g l(
      1). Acetate impurities enriched from about 0.5 g l(-1) in the feed stream to 1.5
      g l(-1) in the concentrate stream solutions. After mono-polar electrodialysis,
      the concentrated sodium lactate solutions were further purified using bi-polar
      electrodialysis. Water transport during bi-polar electrodialysis reached figures
      of 0.070 - 0.222 kg H(2)O per M lactate. Free lactic acid concentration reached
      16% with lactate flux of up to 300 g m(-2) h(-1). Stack energy consumption ranged
      from 0.6 to 1 kW h per kg lactate. Under optimised process conditions current
      efficiency during bi-polar electrodialysis was consistently around 90%. Glucose
      was further reduced from 2 to <1 g l(-1) in the free lactic acid solution. Acetic
      acid impurity remained at around 1 g l(-1). Significant reduction in colour and
      minerals in the product streams was observed during electrodialysis purification.

PMID- 12044554
TI  - Cultivation of Mycobacterium bovis BCG in bioreactors.
AB  - The Mycobacterium bovis BCG vaccine for commercial use is classically produced as
      surface pellicles by culture on synthetic medium. Under these conditions,
      reproducibility of the cultures and quality assessment are hampered by slow
      growth of the bacilli, the formation of bacterial aggregates and a high
      proportion of dead bacilli after processing and final formulation of the vaccine.
      Here, we established dispersed cultures of M. bovis BCG in synthetic media in
      small-scale bioreactors. These cultures allow recording and adjusting of culture
      parameters and give rise to single bacilli with a high degree of live bacteria.
      In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger
      replication and persistence than the vaccine produced under the classical
      conditions. The protective efficacy against challenge with M. tuberculosis was
      identical for both vaccine preparations.

PMID- 12044553
TI  - Chromatographic removal combined with heat, acid and chaotropic inactivation of
      four model viruses.
AB  - The virus removal of protein A affinity chromatography, inactivation capacity,
      acid pH and a combination of high temperature with a chaotropic agent was
      determined in this work. The model viruses studied were sendaivirus, human
      immunodeficency virus (HIV-IIIb), human poliovirus type-II, human herpesvirus I
      and canine parvovirus. The protein A affinity chromatography showed a maximum
      reduction factor of 8 logs in the case of viruses larger than 120 nm size, while
      for small viruses (18-30 nm) the maximum reduction factor was about 5 logs. Non
      viral inactivation was observed during the monoclonal antibody elution step. Low
      pH treatment showed a maximum inactivation factor of 7.1 logs for enveloped
      viruses. However, a weak inactivation factor (3.4 logs) was obtained for DNA
      nonenveloped viruses. The combination of high temperature with 3 M KSCN showed a
      high inactivation factor for all of the viruses studied. The total clearance
      factor was 23.1, 15.1, 13.6, 20.0 and 16.0 logs for sendaivirus, HIV-IIIb, human
      poliovirus type-II, human herpesvirus I and canine parvovirus, respectively.

PMID- 12044555
TI  - Development of an inducible system to assess p94 (CAPN3) function in cultured
      muscle cells.
AB  - p94 belongs to the calpain family of enzymes, also called calcium-activated
      neutral proteases and is mainly expressed in the skeletal muscle. Mutations
      affecting the gene coding for p94 are responsible for a myopathy syndrome called
      Limb Girdle Muscular Dystrophy type 2A (LGMD2A). Although the activity of p94
      seems necessary for muscle function, the biological role of the enzyme is still
      unknown. The goal of this study was to develop a muscle cell line in which the
      expression level of p94 can be regulated, by an inducible way. In this study, a
      biological system was developed which allowed mimicking, in vitro, of part of the
      events occurring in patients (i.e. a decrease of p94 activity). The first results
      indicate that the decrease in p94 activity results in a significant increase of
      myogenin level, a high specific transcription factor involved in myoblast fusion.
      This muscle specific inducible system is an interesting biological tool to assess
      specifically p94 function(s) in cultured muscle cells. According to the present
      results, p94 seems at least to be involved in a myogenesis regulation pathway via
      its action on certain proteins belonging to the myogenic regulator factor family.

PMID- 12044556
TI  - Membrane-facilitated bioproduction of 3-methylcatechol in an octanol/water two
      phase system.
AB  - Bioproduction of 3-methylcatechol from toluene by Pseudomonas putida MC2 was
      studied in the presence of an additional 1-octanol phase. This solvent was used
      to supply the substrate and extract the product, in order to keep the aqueous
      concentrations low. A hollow-fibre membrane kept the octanol and aqueous phase
      separated to prevent phase toxicity towards the bacterium. Volumetric production
      rates increased approximately 40% as compared to two-phase 3-methylcatechol
      production with direct phase contact. Preliminary investigations on downstream
      processing of 3-methylcatechol showed that 1 M of sodium hydroxide selectively
      extracted the disodium salt of 3-methylcatechol into an aqueous phase.

PMID- 12044558
TI  - Skin absorption and human risk assessment.
AB  - A common practice is to assume that percutaneous absorption does not
      significantly contribute to total bioavailability and therefore, absorption
      through other routes is more important to human risk assessment. The skin can
      represent a significant barrier to absorption, but some substances are absorbed
      to a significant extent. Since there is a potential for percutaneous penetration
      that is not consistent between species or substances, the assessment of the
      potential contribution of total body burden from dermal exposures should be
      considered. This review briefly discusses some theories, practices, and factors
      that affect percutaneous absorption with an emphasis on how percutaneous
      absorption evaluations apply to human risk assessment.

PMID- 12044557
TI  - Genotoxicity of idarubicin and its modulation by vitamins C and E and amifostine.
AB  - Idarubicin is an anthracycline anticancer drug used in haematological
      malignancies. The main side effect of idarubicin is free-radicals based
      cardiotoxicity. Using the comet assay we showed that the drug at concentrations
      from the range 0.001 to 10 microM induced DNA damage in normal human lymphocytes,
      measured as the increase in percentage of DNA in the tail (% tail DNA). The
      effect was dose-dependent. Treated cells were able to recover within a 120-min
      incubation. Recognised cell protector, amifostine at 14 mM decreased the mean %
      tail DNA of the cells exposed to idarubicin at all tested concentrations of the
      drug. So did vitamin C at 10 microM, but vitamin E (alpha-tocopherol) at 50
      microM increased the % tail DNA. Lymphocytes exposed to idarubicin and treated
      with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine
      DNA glycosylase II, enzymes recognizing oxidized and alkylated bases, displayed
      greater extent of DNA damage than those not treated with these enzymes.
      Pretreatment of lymphocytes with nitrone spin traps, N-tert-butyl-alpha
      phenylnitrone and alpha-(4-pyridil-1-oxide)-N-tert-butylnitrone decreased the
      extent of DNA damage evoked by idarubicin. To discuss the influence of vitamins
      and amifostine in cancer cells we used also murine pro-B lymphoid BaF3
      transformed with BCR/ABL oncogene. These cells can be treated as model cells of
      human acute myelogenous leukemia. The response of these cells to vitamin E was
      quantitatively the same as human lymphocytes. However, vitamin C did not exert
      any effect on DNA damage and amifostine, in spite to normal lymphocytes,
      potentiated this effect. The results obtained suggest that reactive oxygen
      species, including free radicals, may be involved in the formation of DNA lesions
      induced by idarubicin. The drug can also methylate DNA bases. Our results
      indicate that not only cardiotoxicity but also genotoxicity and in consequence
      induction of secondary malignancies should be taken into account as diverse side
      effects of idarubicin. Amifostine may potentate DNA-damage effect of idarubicin
      in cancer cells and decrease this effect in normal cells. Vitamin C can be
      considered as protective agents against DNA damage in normal cells in persons
      receiving idarubicin-based chemotherapy, but the use of vitamin E cannot be
      recommended and at least needs further research.

PMID- 12044559
TI  - Induction of epidermal proliferation and expressions of PKC and NF-kappaB by
      betel quid extracts in mouse: the role of lime-piper additives in betel quid.
AB  - Components of betel quid (BQ) have been investigated for genotoxicity,
      mutagenicity, and animal toxicity. However, little information exists regarding
      their carcinogenic characteristics. Considerable attention has already been
      focused on tumor promoters that occur environmentally for human uptake. In this
      study, the promoting effects of BQ and lime-piper additives (LPA) in BQ on
      epidermal hyperplasia in CD-1 mouse skin are investigated. In the present study,
      we found that BQ and LPA at concentrations of 25,50,75 mg/ml caused significant
      induction of hyperplasia, but only LPA caused an increase of epidermal ornithine
      decarboxylase (ODC). Treatment of mouse skin with LPA caused remarkable increases
      in the production of H(2)O(2) by 2.41-, 3.90-, and 3.76-fold (for the above
      indicated concentrations respectively); as well as marked increases of
      myeloperoxidase (MPO) by 1.43-, 2.70-, and 2.29-fold. Application of LPA or BQ
      (50,100,150 mg/ml) also caused induction of protein kinase C-alpha (PKC-alpha)
      and NF-kappaB. LPA exhibited more significant effect than BQ. Thus, LPA might
      make a major contribution to the BQ-induced expression of PKC and NF-kappaB.
      These results indicated that BQ has the potential of being promoting agents, and
      that LPA should play a major role in increasing the effects of BQ-caused skin
      hyperplasia and inflammation. The promoting effects of BQ and LPA on mouse skin
      were associated with the induction of the expressions of PKC and NF-kappaB.

PMID- 12044560
TI  - A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione
      synthetase in crude extracts from tissues and cultured mammalian cells.
AB  - An assay of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione
      synthetase (GS) in crude extracts of cultured cells and tissues is described. It
      represents a novel combination of known methods, and is based on the formation of
      glutathione (GSH) from cysteine, glutamate and glycine in the presence of rat
      kidney GS for the assay of gamma-GCS, or from gamma-glutamylcysteine and glycine
      for the assay of GS. GSH is then quantified by the Tietze recycling method. Assay
      mixtures contain the gamma-glutamyl transpeptidase (GGT) inhibitor acivicin in
      order to prevent the degradation of gamma-glutamylcysteine and of the
      accumulating GSH, and dithiothreitol in order to prevent the oxidation of
      cysteine and gamma-glutamylcysteine. gamma-GCS and GS levels determined by this
      method are comparable to those determined by others. The method is suitable for
      the rapid determination of gamma-GCS GS in GGT-containing tissues and for the
      studies of induction of gamma-GCS and GS in tissue cultures.

PMID- 12044561
TI  - Formation of 8-nitroguanine in tobacco cigarette smokers and in tobacco smoke
      exposed Wistar rats.
AB  - Our previous studies have shown that 8-nitroguanine (8-NO(2)-G) could serve as a
      specific biomarker of DNA damage induced by gaseous nitrogen oxides (NO(x))
      exposure. To evaluate the effect of tobacco cigarette smoking on the DNA damage
      in peripheral lymphocytes of cigarette smoke ones, we randomly collected and
      determined the level of 8-NO(2)-G in DNA extracted from peripheral lymphocyte of
      15 each of light-smoking healthy volunteer (L-S, less than one pack per day),
      moderate-smoking healthy volunteers (M-S, one to two pack per day for 5-10
      years), heavy-smoking healthy volunteers (H-S, over two packs per day for 10
      years), lung cancer patients with heavy smoking (cancer H-S) and non-smoking
      healthy controls. Both of the mean level of the 8-NO(2)-G levels in peripheral
      lymphocyte (0.90+/-1.0, 1.23+/-1.14, 1.43+/-0.79, 3.62+/-1.38 ng per microg DNA)
      and serum nitrite (38.99+/-9.58, 46.70+/-9.38, 55.46+/-10.45, 70.1+/-18.54
      microM) of L-S, M-S, H-S and cancer H-S groups were higher than that of non
      smoking healthy controls (0.02+/-0.04 and 18.96+/-4.31 for 8-NO(2)-G level and
      serum nitrite, respectively). Furthermore, in animal experiment, a dose-dependent
      increase in 8-NO(2)-G was observed in rat lung and peripheral lymphocyte DNA of
      Wistar rats after tobacco cigarette smoke exposure twice a day, for 1 month. The
      level of 8-NO(2)-G is 0.17+/-0.41, 1.65+/-3.15, 23.50+/-20.75 and 37.58+/-17.55
      ng per microg lung DNA for rat exposed with tobacco cigarette smoke from 0, 5,
      10, 15 cigarettes per day, respectively. It was also found that count of
      peripheral lymphocytes and nitrite concentration in serum of rat increased after
      the tobacco smoke exposure. It is postulated that tobacco cigarette smoking could
      induce DNA damage (8-NO(2)-G formation) by exo- and endogenous NO(x).

PMID- 12044562
TI  - Cytochrome P450IIE1 (CYP2E1) is induced by skatole and this induction is blocked
      by androstenone in isolated pig hepatocytes.
AB  - Skatole, a derivative of tryptophan, is produced in the hind-gut of pigs and is
      metabolised via hepatic cytochrome P4502E1 (CYP2E1). Excessive accumulation of
      skatole together with androstenone, a metabolite of testosterone, in adipose
      tissue in some pigs is a major cause of 'boar taint' and is associated with
      defective expression of CYP2E1. This phenomenon is not understood because factors
      regulating CYP2E1 expression in pig liver have not yet been characterised.
      Therefore effects of skatole and androstenone on CYP2E1 expression were studied
      using isolated pig hepatocytes as a model system. Skatole induced CYP2E1 protein
      expression to the same degree as did acetone, a known CYP2E1 inducer. Induction
      by skatole was maximum between 20 and 28 h and a half-maximum effect was obtained
      at a skatole concentration of 0.2 mM. Induction of CYP2E1 by skatole was protein
      synthesis dependent. Androstenone antagonised the effect of skatole on CYP2E1
      expression but did not affect the CYP2E1 protein level when added alone. These
      results suggest that defective expression of CYP2E1 in some pigs is due to
      excessive concentrations of androstenone which prevent CYP2E1 induction by its
      substrate skatole. As a result, skatole metabolism is reduced and skatole is
      accumulated in adipose tissue.

PMID- 12044563
TI  - Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo
      skin penetration.
AB  - The aim of this study was the comparison of two different formulations (solid
      lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for
      the molecular sunscreen oxybenzone. The influence of the carrier on the rate of
      release was studied in vitro with a membrane-free model. The release rate could
      be decreased by up to 50% with the SLN formulation. Further in vitro measurements
      with static Franz diffusion cells were performed. In vivo, penetration of
      oxybenzone into stratum corneum on the forearm was investigated by the tape
      stripping method. It was shown that the rate of release is strongly dependent
      upon the formulation and could be decreased by 30-60% in SLN formulations. In all
      test models, oxybenzone was released and penetrated into human skin more quickly
      and to a greater extent from the emulsions. The rate of release also depends upon
      the total concentration of oxybenzone in the formulation. In vitro-in vivo
      correlations could be made qualitatively.

PMID- 12044564
TI  - Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled
      by hydrophilic additives.
AB  - We investigated the controlled release of human insulin at an initial stage from
      poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA
      microcapsules were prepared by the novel solvent evaporation multiple emulsion
      process. When the crystalline insulin was dispersed in dichloromethane as solid
      in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid
      on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA
      microcapsules exhibited marked rapid release of insulin within several hours in
      both in vivo and in vitro experiments. On the other hand, the addition of
      glycerol or water in the primary dichloromethane dispersion results in
      drastically suppressed initial release. It was found by SEM observation that
      water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean
      diameter of 300-500 nm were formed in this primary solution. This phenomenon can
      be theoretically presumed to occur because insulin and PLGA molecules, having
      amphiphilic properties, converge on the interface between the hydrophilic
      additive and dichloromethane. Hence, insulin molecules heterogeneously located in
      the inside of PLGA microcapsules, not on the surface, would be gradually released
      with PLGA hydrolytic decomposition. As an additional effect of glycerol, the
      initial burst was further suppressed due to the decrease of the glass transition
      temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA
      molecules took place at around 37 degrees C, the porous structure of microspheres
      immediately disappeared after immersion in PBS or subcutaneous administration.
      The insulin diffusion through the water-filled pores would be effectively
      prevented. The strict controlled initial release of insulin from the PLGA
      microsphere suggested the possibility of utilization in insulin therapy for type
      I diabetic patients who need construction of a basal insulin profile.

PMID- 12044565
TI  - Degradation of and drug release from a novel 2,2-bis(2-oxazoline) linked
      poly(lactic acid) polymer.
AB  - The degradation rate of poly(lactic acid) (PLA) is typically modified by
      copolymerization of the glycolide with lactide. In the present study, the
      degradation rate of PDLLA was modified by a novel linking of PLA with 2,2'-bis(2
      oxazoline). This modification resulted in formation of a more rapidly degrading
      poly(ester amide) (PEA) for controlled drug release. The hydrolytic degradation
      of PDLLA and PEA films was studied in PBS (pH 7.4, USP XXIV, 37 degrees C); the
      resulting decrease in molecular weight was determined by size exclusion
      chromatography and the weight loss of films was measured. Drug releases of
      guaifenesin (mw 198.2), timolol (mw 332.4), sodium salicylate (mw 160.1) and FITC
      dextran (mw 4400) from PDLLA and PEA films and microspheres were examined in PBS
      (pH 7.4, 37 degrees C). The degradation rate of PEA was substantially greater
      than that of PDLLA. The release profiles of all small model drugs (mw <332.4)
      from PDLLA films were biphasic or triphasic, while the release profiles of small
      model drugs from PEA films varied extensively. Due to the faster weight loss of
      PEA, FITC-dextran (mw 4400) was released substantially more rapidly from PEA
      microspheres than from PDLLA microspheres. In conclusion, all model drugs, except
      guaifenesin, were released faster from PEA preparations than from PDLLA
      preparations.

PMID- 12044566
TI  - Sustained release of etanidazole from spray dried microspheres prepared by non
      halogenated solvents.
AB  - Etanidazole, a kind of radiosensitizer, was encapsulated in the spray-dried
      microspheres using biodegradable polymer PLGA 65:35 as the carrier for controlled
      release applications. Two non-halogenated solvents, e.g., ethyl acetate (EA) and
      ethanol, were tested to modify the properties of microspheres prepared by the
      commonly used solvent dichloromethane (DCM) alone. Their effects on the release
      behavior, morphology, particle size, and encapsulation efficiency of etanidazole
      loaded microspheres were determined, and results were compared with DCM. The
      particle formation process via spray drying technique was also analyzed in order
      to understand the results obtained. It was found that larger percentage of EA (in
      the solvent mixture consisting of DCM and EA) in the fabrication of PLGA 65:35
      microspheres decreases the initial burst, release rate and prolongs the release
      duration of etanidazole. In contrast to the spherical and porous microspheres
      prepared by DCM, the microspheres prepared by the solvent EA are all nonporous
      with a doughnut like surface structure due to its comparatively rapid phase
      transition (phase inversion) but slow solvent evaporation rate (longer time
      required to solidify). Increasing the polymer concentration (e.g., 4%, w/v) can
      bring about much more spherical microspheres by spray drying. Although ethanol,
      as a co-solvent, can dissolve a higher amount of etanidazole and lead to a higher
      drug encapsulation efficiency, the addition of ethanol in the DCM solvent can
      significantly increase the initial burst and the release rate of the microspheres
      due to the inhomogeneous drug distribution and structure of microspheres caused
      by phase separation. This study shows that ethyl acetate is an excellent low
      toxic solvent that can be used in the spray drying technique for decreasing the
      initial burst, prolonging the release duration of a highly water-soluble drug
      like etanidazole. The use of EA provides a promising way to develop a sustained
      release system for etanidazole and other highly water-soluble drugs.

PMID- 12044567
TI  - Behavior of mucoadhesive nanoparticles having hydrophilic polymeric chains in the
      intestine.
AB  - The behavior of nanoparticles having surface hydrophilic poly(N
      isopropylacrylamide), poly(N-vinylacetamide), poly(vinylamine) or
      poly(methacrylic acid) chains in the intestine was examined. The permeability of
      salmon calcitonin (sCT) from the mucosal to serosal side of the everted jejunum
      was enhanced in the presence of nanoparticles. This enhancement, which correlated
      with the amount of sCT incorporated in nanoparticles, disappeared completely
      after removal of the mucous layer. When fluorescein isothiocyanate-dextran (FD-4)
      was used instead of sCT, its permeability through the everted jejunum with and
      without mucous layer was not enhanced by any nanoparticles, because FD-4 was not
      incorporated in nanoparticles at all. These findings indicated that the
      accumulation of nanoparticles incorporating sCT in the mucous layer resulted in
      the enhancement of sCT permeability. Nanoparticles with poly(N
      isopropylacrylamide) or poly(vinylamine) on their surfaces did not cause any
      damage to the intestinal mucosa. Also, none of the nanoparticles opened the tight
      junction of the intestinal membrane. It was concluded that mucoadhesion of
      nanoparticles incorporating sCT to the gastrointestinal mucosa contributed to the
      absorption enhancement of sCT.

PMID- 12044568
TI  - Bioadhesive microdevices with multiple reservoirs: a new platform for oral drug
      delivery.
AB  - A variety of delivery systems have been devised, in recent years, to improve the
      oral bioavailability of drugs including enterically coated tablets, capsules,
      particles, and liposomes. Microfabrication technology may offer some potential
      advantages over conventional drug delivery technologies. This technology,
      combined with appropriate surface chemistry, may permit the highly localized and
      unidirectional release of drugs, permeation enhancers, and/or promoters. In this
      study, we demonstrate the fabrication of prototype reservoir-containing
      microdevices and a surface chemistry protocol that can be used to bind lectin via
      avidin-biotin interactions to these micromachined drug delivery vehicles. The use
      of microfabrication allows one to tailor the size, shape, reservoir volume, and
      surface characteristics of the drug delivery vehicle. In vitro studies show
      enhanced bioadhesion of these lectin conjugated silicon microdevices. This
      approach may be used to improve the absorption of pharmacologically active
      biopolymers such as peptides, proteins and oligonucleotides into circulation at
      targeted sites in the GI system via the creation of a robust hybrid
      organic/inorganic delivery system. This paper describes one of the first
      applications of microfabrication to oral drug delivery.

PMID- 12044569
TI  - Encapsulation-induced aggregation and loss in activity of gamma-chymotrypsin and
      their prevention.
AB  - Development of alternative procedures to the commonly employed water-in-oil-in
      water technique to encapsulate proteins in polymers is needed due to protein
      stability issues. Herein the model protein gamma-chymotrypsin has been
      encapsulated in poly(D,L-lactic-co-glycolic)acid (PLGA) microspheres using the
      solid-in-oil-in-water (s/o/w) encapsulation technique. The model protein was
      chosen because it has a measurable biological activity and its unfolding is
      irreversible. The latter make the protein an excellent sensor for unfolding
      events in the encapsulation procedure. While lyophilization did not cause any
      irreversible aggregation or loss in activity, encapsulation of the lyophilized
      enzyme by the s/o/w technique proved detrimental to its integrity. Specifically,
      34% of the encapsulated protein was aggregated and the specific activity of
      enzyme released within 24 h was reduced to ca. 50% of that prior to
      encapsulation. FTIR spectra demonstrated substantial encapsulation-induced
      perturbations of the secondary structure of gamma-chymotrypsin. To achieve
      stabilization of gamma-chymotrypsin during encapsulation, excipients were
      employed during the initial lyophilization process. When gamma-chymotrypsin was
      co-lyophilized with poly(ethylene glycol) (PEG) the formation of non-covalent
      aggregates inside the microspheres decreased significantly to 8%. FTIR data
      showed that PEG prevented encapsulation-induced structural perturbations. In
      contrast, the amount of aggregates remained high (34%) when gamma-chymotrypsin
      was co-lyophilized with trehalose. No additional non-soluble aggregates were
      formed during 1 week of in vitro release. Furthermore, the amount of non-soluble
      aggregates in the microspheres after encapsulation correlated with the amount of
      non-released protein. Therefore in vitro release did not cause aggregation.
      Similar results were found with respect to the retention of the specific enzyme
      activity where PEG afforded excellent stability.

PMID- 12044570
TI  - A thermodynamic study of cationic polymer-plasmid DNA complexes by highly
      sensitive differential scanning calorimetry.
AB  - The characteristics of polymer-DNA complexes formed by positively-negatively
      charged interaction have a great influence on their transfection potential. Since
      the limit changes in thermal transitions which were hardly measured in
      conventional calorimetry, now in this study they have been successfully carried
      out by highly-sensitive differential scanning calorimetry for better
      understanding the pDMAEMA-plasmid DNA complexing process. Thermal behaviors of
      plasmid DNA, polymer and their formed complexes were recorded to give insights
      into their conformational changes when temperature was raised. In results, the
      supercoiled or open-circular plasmid DNA is not thermal reversible indicated by
      the decrease of denaturation peak and disappearance of DNA conformational
      transition related to its twist status at 50-70 degrees C. The cationic polymer
      is thermally stable by showing reversible transition peaks after two heating
      processes. For the cationic polymer-plasmid DNA complexes, electrostatic forces
      lead to a higher denaturation temperature of plasmid DNA and transition
      temperature of polymer. Also, heat can cause a topological change in plasmid DNA
      and then change their mutual complexation capacity.

PMID- 12044571
TI  - Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl
      pyrrolidone) and poly(acrylic acid) prepared by template polymerization.
AB  - To develop a new mucoadhesive drug carrier, poly(vinyl pyrrolidone)
      (PVP)/poly(acrylic acid) (PAA) interpolymer complexes were prepared by the
      template polymerization of acrylic acid using PVP as a template polymer. Fourier
      transform infrared results showed that the interpolymer complexes were formed by
      hydrogen bonds between the carboxyl groups of PAA and the carbonyl groups of PVP.
      The adhesive forces of the PVP/PAA interpolymer complexes were higher than that
      of commercial Carbopol 971. Moreover, the adhesive force and the release rate can
      be controlled by changing the mole ratios of PVP and PAA. The release rates of
      ketoprofen from the PVP/PAA interpolymer complexes showed pH-dependency, and were
      slower at lower pH. The release rate of ketoprofen from the complex seemed to be
      mainly controlled by the dissolution rate of the complex above a pK(a) of PAA
      (4.75) and by the diffusion rate below the pK(a). The prepared complex appears to
      be an adequate carrier for the mucoadhesive drug delivery system.

PMID- 12044572
TI  - Controlled transport of timolol maleate through artificial membranes under
      passive and iontophoretic conditions.
AB  - The passive and iontophoretic permeability of timolol maleate (TM) through porous
      and dense artificial membranes was investigated in order to select the most
      optimal membrane for a transdermal drug delivery system. For the meso-porous
      membranes (pore diameter 2-50 nm), the TM permeability for passive diffusion and
      iontophoresis was practically the same. For the micro-porous membranes (pore
      diameter<2 nm), a significant transport contribution of iontophoresis was
      observed, which was more pronounced when higher current densities were applied.
      The electrical resistance of all the porous membranes was lower than the
      electrical resistance of human skin. For dense membranes, passive and
      iontophoretic TM permeability was significantly lower than for porous membranes
      and in most cases their electrical resistance was comparable or even higher than
      the resistance of human skin. For most of the membranes studied the average
      adsorption of TM at 37 degrees C was low (0.02-0.33 mg/cm(2)) and independent of
      the TM concentration. For the meso-porous mixed cellulose acetate-cellulose
      nitrate membrane the TM adsorption was significantly higher and increased with
      the TM concentration. Based on our results, the optimum membrane for an
      iontophoretic transdermal TM delivery system is the LFC 1 micro-porous membrane
      because it mainly controls the TM delivery (TM iontophoretic permeability: 0.86 x
      10(-6) cm/s), has very low electrical resistance (0.9-1.5 komega cm(2)) and the
      TM adsorption to it is low (0.15 mg/cm(2)). The therapeutic plasma TM
      concentration is achievable by application of this membrane in realistic sizes (5
      64 cm(2)) and by application of current densities between 0.13 and 0.5 mA/cm(2).

PMID- 12044573
TI  - Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery
      system for clotrimazole.
AB  - It was the purpose of this study to design and evaluate a new bioadhesive vaginal
      drug delivery system for clotrimazole. Chitosan, a cationic biopolymer derived by
      deacetylation of chitin, was modified by the introduction of thioglycolic acid
      (TGA). The modification was achieved by utilising a carbodiimide to link the
      carboxylic acid moieties of TGA covalently to the primary amino groups of
      chitosan. The amount of added carbodiimide was thereby varied, resulting in
      chitosan-TGA conjugates A and B with 160 microM (=micromol) and 280 microM thiol
      groups per gram polymer, respectively. In order to characterise the new polymers
      the water uptake, the disintegration behaviour, the bioadhesive properties
      utilising the rotating cylinder method, as well as the release of clotrimazole
      from tablets based on these derivatives were studied. The water uptake and
      cohesive properties of vaginal tablets consisting of these new conjugates could
      be significantly (p<0.05) improved. By adding clotrimazole the disintegration
      time of the conjugates was prolonged 1.6-fold for conjugate A and even 100-fold
      for conjugate B. Furthermore, the adhesion on vaginal mucosal tissue could be
      significantly improved. The addition of clotrimazole had also an impact on the
      adhesion time of chitosan-TGA conjugate B, which remained 26-times longer on
      vaginal mucosa than the corresponding unmodified polymer. The immobilisation of
      thiol groups guarantees a controlled drug release. Results of this study
      demonstrate that these new chitosan-TGA conjugates are very promising vehicles
      for the vaginal application of clotrimazole in treatment of mycotic infections.

PMID- 12044574
TI  - Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell
      monolayers.
AB  - The objective of this study was to investigate the influence of physiochemical
      parameters (such as size, molecular weight, molecular geometry, and number of
      surface amine groups) of poly (amidoamine) (PAMAM) dendrimers, on their
      permeability across Caco-2 cell monolayers. The permeability of a series of PAMAM
      dendrimers, generations 0-4 (G0-G4), was investigated across Caco-2 cell
      monolayers in both the apical to basolateral (AB) and basolateral to apical (BA)
      directions. The influence of PAMAM dendrimers on the integrity, paracellular
      permeability, and viability of Caco-2 cell monolayers was also monitored by
      measuring the transepithelial electrical resistance (TEER), mannitol
      permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively.
      G0, G1 and G2 demonstrated similar AB permeabilities, which were moderate several
      fold higher than the AB permeability of higher generations. The AB and BA
      permeability of G0-G4 typically increased with the increase in donor
      concentration and incubation time. Permeability values are not reported at
      generations, concentrations or incubation times that the dendrimers were toxic to
      Caco-2 cells. TEER values decreased and mannitol permeability increased as a
      function of donor concentration, incubation time, and generation number. LDH
      results for G3 and G4 indicate that Caco-2 cell viability was reduced with
      increasing donor concentration, incubation time, and generation number. The
      appreciable permeability of G0-G2, coupled with their nontoxic effects on Caco-2
      cells, suggest their potential as water-soluble polymeric drug carriers for
      controlled oral drug delivery.

PMID- 12044575
TI  - Preparation of theophylline hydrogels of atactic poly(vinyl alcohol)/NaCl/H2O
      system for drug delivery system.
AB  - Theophylline (TH) was loaded in an a-PVA/NaCl/H2O hydrogels system by one cycle
      gelation only at -20 degrees C. However, it developed some unwanted crystal-like
      structure surrounding the hydrogels while kept at room temperature. The physical,
      chemical and thermal analyses of this crystal-like structure indicated TH
      embedded with thin hydrogels of a-PVA/NaCl. Later during dissolving of feed
      mixture at least 3 h heat treatment with proper mixing at high temperature
      contributed hydrogels of almost no crystal-like structure. 3% of TH was
      successfully loaded by this way. This type of hydrogels showed Fickian type drug
      release (Higuchi Model) and it showed a more sustained effect than that of
      traditional cyclic FT. Comparatively lower release rate, diffusion coefficient
      and kinetic constant values of this system prevail over other systems studied
      here. A DSC thermogram revealed that apparently homogeneous microgel junctions
      might play the key role behind the above properties. Moreover the a
      PVA/TH/NaCl/H2O system depresses the freezing point at -30 degrees C instead of
      above this temperature. The hydrogels of this system were also prepared by
      freezing at -30 degrees C for 16 h as one cycle. Three cycles were done in cyclic
      FT (freezing at -30 degrees C for 16 h and thawing at room temperature for 8 h).
      Drug release was studied for a total of 750 min. Up to the asymptotic value, 10.5
      h TH release from the hydrogel matrices of the a-PVA/NaCl/H2O system (gelation at
      -20 degrees C) and 6.5 h from those of a-PVA/NaCl/H2O (freezing at -30 degrees C)
      and a-PVA/H2O systems (cyclic FT) were found.

PMID- 12044576
TI  - Intranasal gene delivery with a polyethylenimine-PEG conjugate.
AB  - Polyethylenimines (PEIs) are among the most efficient synthetic DNA carriers.
      High levels of reporter gene expression can be obtained with these agents on a
      variety of cells. Nevertheless, the gap between their efficiency and that
      required for therapeutic approaches is still important. With the aim to improve
      the in vivo transfection properties of PEIs, we have synthesized a conjugate
      consisting of the linear polymer of 22 kDa covalently modified with
      polyethyleneglycol (PEG) residues. The resulting conjugate was able to complex
      DNA and allowed the preparation of highly concentrated polyplexes, in contrast to
      non-modified PEIs. Administration by nasal instillation of PEI-PEG/DNA complexes
      in mice resulted in significant levels of transgene expression. Luciferase
      activity was greatest 24 h after delivery and decreased thereafter. Our results
      show that the grafting of PEGs can improve some of the properties of PEIs.

PMID- 12044578
TI  - Modern aspects of atherosclerosis and treatment of lipid disorders.

PMID- 12044579
TI  - The extracellular matrix on atherogenesis and diabetes-associated vascular
      disease.
AB  - Atherosclerosis is remarkably increased in type 2 diabetes suggesting that
      mechanisms causing arterial lesion are enhanced by the metabolic disturbances of
      insulin resistance (IR) and diabetes. Several lines of research suggest that
      processes taking place in the arterial intima extracellular matrix may be part of
      a shared pathogenic mechanism. The intima extracellular matrix is where
      atherogenesis takes place. This layer contains fibrilar macromolecules like
      collagens, proteoglycans (PGs), hyaluronate, and extracellular multi-domain
      proteins. Specific interaction of lysine, arginine-rich segments of the apoB-100
      lipoproteins, LDL, IDL and Lp (a), with the negatively charged glycosaminoglycans
      (GAGs) of PGs cause retention of the lipoproteins, one of the initiation process
      of atherogenesis. Such interactions cause structural modifications of the lipid
      and protein moieties of the lipoproteins that appear to increase their
      susceptibility to proteases, phospholipases and free radical-mediated processes.
      The association of apoB-lipoproteins, specially small and dense LDL, with intima
      PGs increases their uptake by macrophages and human arterial smooth muscle cells
      (HASMC) leading to 'foam cell' formation. In vitro, elevated levels of non
      esterified fatty acids (NEFA) alter the matrix of endothelial cells basement
      membrane making them more permeable to macromolecules. NEFA cause changes in the
      expression of genes controlling the PGs composition of the PGs secreted by HASMC
      causing formation of a matrix with high affinity for LDL. These results lead us
      to speculate that an important component of the dyslipidemia of IR and type 2
      diabetes, chronic high NEFA, may contribute to cellular alterations that cause
      changes of the arterial intima extracellular matrix. Such changes may increase
      the atherogenicity of the retention of apoB lipoproteins in the intima and
      contribute to the systemic alteration of the arterial wall frequently observed in
      IR and type 2 diabetes.

PMID- 12044580
TI  - Endothelial function in the post-prandial state.
AB  - In recent years the endothelium has emerged as an important protective barrier
      against the development of atherosclerosis. Endothelial dysfunction, often
      characterised by impaired endothelium-dependent vasodilation, is generally
      considered to be an early marker of cardiovascular disease. Recently, it has been
      noted that the post-prandial state is associated with impaired endothelium
      dependent vasodilation. Since man lives in a post-prandial state most of the day,
      prolonged exposure to dietary factors which impair endothelial function or
      delayed post-prandial recovery of the endothelium could negatively affect the
      cardiovascular risk profile. This review will focus on post-prandial endothelial
      function characterised by endothelium-dependent changes in vasomotion.

PMID- 12044581
TI  - Immunosuppressive effects of statins.
AB  - 3-Hydroxy-3-methhylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or
      statins, are effective lipid lowering agents, extensively used in medical
      practice [Circulation 2000;101:207; J Am Med Assoc 2000;283:2935]. Statins have
      never been shown to be involved in the immune response, although reports have
      suggested a better outcome of cardiac transplantation in patients under
      pravastatin therapy [New Engl J Med 1995;333:621; Circulation 1997;96:1398].
      Major histocompatibility complex class II (MHC class II) molecules are directly
      involved in the activation of T lymphocytes and in the control of the immune
      response. Whereas only a limited number of specialized cell types express MHC-II
      constitutively, numerous other cells become MHC-II positive upon induction by
      interferon-gamma (IFN-gamma) [Annu Rev Immunol 1996;14:301]. This complex
      regulation is under the control of the transactivator CIITA [Science
      1994;265:106]. Recently, we demonstrated that statins act as direct inhibitors of
      induction of MHC-II expression by IFN-gamma and thus as repressors of MHC-II
      mediated T cell activation [Nat Med 2000;6:1399; Swiss Med Wkly 2001;131:41].
      This effect of statins is due to inhibition of the inducible promoter IV of the
      transactivator CIITA. Interestingly, this inhibition is specific for inducible
      MHC-II expression and does not concern constitutive expression of CIITA and MHC
      II. In repressing induction of MHC-II, and subsequent T lymphocyte activation,
      statins therefore behave as a novel type of immunomodulator. This unexpected
      effect provides a scientific rationale for suggesting the use of statins as novel
      immunosuppressors, not only in organ transplantation but in numerous other
      pathologies as well.

PMID- 12044582
TI  - Statins and ischemic stroke.
AB  - The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors or statins are
      potent inhibitors of cholesterol synthesis. Several large clinical trials have
      demonstrated that these agents reduce serum cholesterol levels and the incidence
      of cardiovascular diseases. However, overlap and meta-analyses of these clinical
      trials suggest that the beneficial effects of statins may extend beyond their
      effects on serum cholesterol levels. Because statins also inhibit the synthesis
      of isoprenoid intermediates in the cholesterol biosynthetic pathway, they may
      have pleiotropic effects on the vascular wall. In particular, the ability of
      statins to decrease the incidence of ischemic stroke highlights some of their non
      cholesterol effects since serum cholesterol levels are poorly correlated with the
      risk for ischemic stroke.

PMID- 12044583
TI  - Coronary artery disease and dyslipidemia within Europe: genetic variants in lipid
      transport gene loci in German subjects with premature coronary artery disease.
AB  - Fifteen polymorphisms in six lipid transport genes were studied in a German
      population for relationships with dyslipidemia and coronary artery disease (CAD),
      to investigate a possible genetic basis for the marked differences in mortality
      rates from coronary heart disease within Europe. In other populations these
      polymorphisms have all been associated with CAD or with phenotypes known to
      predispose to CAD. The apoAI PstI polymorphism (P<0.005) and the lipoprotein
      lipase Ser(447)-Ter mutation (P<0.005) were associated with plasma triglyceride
      concentrations. Additionally, the apoAI PstI polymorphism (P<0.05), the apoB XbaI
      polymorphism (P<0.05) and apoE phenotypes (P<0.05) were associated with plasma
      cholesterol concentrations. However, none of the allele frequencies of the
      polymorphisms studied were related to the presence, or absence, of coronary
      artery disease. Associations between five polymorphisms representing four lipid
      transport gene loci and dyslipidemia were demonstrated in this German population.
      It is possible that predisposition to dyslipidemia in Germany involves a
      particular selection of polymorphic loci, which are different from those
      identified in other European countries.

PMID- 12044584
TI  - Pharmacological interactions of statins.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (statins) are effective in reducing the risk of coronary events, and are
      generally very well tolerated. However, simvastatin, lovastatin, cerivastatin and
      atorvastatin are biotransformed in the liver primarily by cytochrome P450 (CYP)
      3A4, and clinical experience has shown that the risk of adverse effect, such as
      myopathy, increases with concomitant use of statins with drugs that substantially
      inhibit CYP 3A4 at therapeutic doses. Indeed, pharmacokinetic interactions (e.g.
      increased bioavailability), myositis, and rhabdomyolysis have been reported
      following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin
      and cyclosporine A, mibefradil or nefazodone. In contrast, fluvastatin (mainly
      metabolized by CYP 2C9) and pravastatin (eliminated by other metabolic routes)
      are less subject to this interaction. Nevertheless, an increase in pravastatin
      bioavailability has been reported in the presence of cyclosporine A, possibly
      because of an interaction at the level of biliary excretion. In summary, some
      statins may have lower adverse drug interaction potential than others, which is
      an important determinant of safety during long-term therapy.

PMID- 12044585
TI  - Postprandial lipemia--effect of lipid-lowering drugs.
AB  - Exaggerated postprandial hyperlipidemia has been associated with cardiovascular
      disease. The mechanisms underlying this association are likely to depend on a
      multitude of effects. Potentially atherogenic remnants of triglyceride-rich
      lipoproteins (TRL) accumulate in the postprandial state. In addition, TRL may
      promote the formation of small dense LDL. There are some indications that the
      postprandial period is a hypercoagulable state and endothelial function seems to
      be hampered after acute fat intake. Conventional lipid lowering drugs such as
      statins and fibrates have the potency of reducing postprandial hyperlipidemia,
      but the fibrates seem to be more effective in this respect. There is a complete
      lack of prospective studies linking inefficient postprandial lipid metabolism
      with clinical endpoints and there is also a need to include investigations of
      postprandial lipid metabolism in the evaluation of novel drugs affecting lipid
      metabolism and insulin resistance.

PMID- 12044586
TI  - Diabetic dyslipidemia.
AB  - By the year 2025, there will be more than 300 million type 2 diabetes sufferers
      worldwide. This epidemic will be followed by a wave of cardiovascular disease.
      Diabetes is in fact a serious vascular disease with poor prognosis, and not only
      a disease characterized by elevated blood glucose. If adequate attention were
      paid to this, it would be much easier to relieve the burden of cardiovascular
      disease in type 2 diabetes patients. One important cardiovascular risk factor in
      type 2 diabetic people is dyslipidemia. This is characterized by low HDL
      cholesterol, high serum VLDL-triglycerides, and a preponderance of small, dense
      LDL. Even slight elevations of LDL-cholesterol in type 2 diabetic patients are
      associated with a substantial increase in cardiovascular risk. The composition of
      lipid particles in diabetic dyslipidemia is more atherogenic than in dyslipidemia
      in general. This means in turn that normal lipid concentrations are more
      atherogenic in diabetic than in non-diabetic patients. Retrospective analyses
      show that, in terms of protection from cardiovascular endpoints, the benefit of
      lipid lowering in type 2 diabetic patients is at least as great as in the non
      diabetic population. Lowering of LDL-cholesterol is a very attractive target for
      the reduction of coronary heart disease in type 2 diabetic people.

PMID- 12044587
TI  - The choice of hormone replacement therapy or statin therapy in the treatment of
      hyperlipidemic postmenopausal women.
AB  - Evidence based treatment of cardiovascular risk factors on outcome in women is
      still inconclusive given the very large numbers needed to achieve a significant
      difference in cardiovascular event. Although numerous studies of the effect of
      hormone replacement therapy (HRT) on risk factors have suggested benefit, the
      only data from a randomised control trial of HRT in secondary prevention was
      neutral. Coronary disease-primary prevention: (a) Statins: Air Force/Texas
      Coronary Atherosclerosis Prevention Study (AFCAPS/TEX CAPS). The only randomised
      controlled trial (RCT) to include women. There were fewer coronary heart disease
      (CHD) events in women but no difference in mortality. (b) HRT: no completed RCT
      the results from Womens Health Initiative (WHI) and Women Intervention Study of
      Long Duration of Oestrogen in the Menopause (WISDOM) are awaited, the former
      likely to complete in 2004. There are numerous reports of positive observational
      epidemiological studies for HRT. There is little evidence for statin use in women
      who will probably not qualify for treatment on global CHD risk assessment,
      familial hypercholesterolemia and type 2 diabetes excepted. HRT is, therefore,
      not only appropriate for its multiple effects on lipoproteins, vascular function
      and insulin sensitivity but also for prevention of osteoporosis. Coronary disease
      SECONDARY PREVENTION: (a) Statins: the major measurable effect of these drugs is
      to reduce total and LDL cholesterol. In RCT trials, the Scandanavian Simvastatin
      Survival Study (4S), the Cholesterol and Recurrent Event (CARE) and Long-term
      Intervention with Pravastatin in Ischaemic Disease (LIPID), approximately 20% of
      subjects were female, in whom CHD events, but not CHD or total mortality were
      reduced. (b) HRT: there is data available from a single RCT of continuous
      combined premarin and medroxyprogesterone acetate (MPA) against placebo, The
      Heart Estrogen Replacement Study (HERS). A study of 2763 women and mean duration
      of 4.1 years. This study was neutral, with no reduction in CHD events or
      mortality. There were more events in the first year, and fewer in years 3-5.
      Other studies of HRT have been observational and positive for HRT. The effects of
      treatment on lipoproteins with statins, HRT and combination of statin and HRT
      have been investigated. In secondary prevention for hyperlipidemic women to
      achieve cholesterol <5, low density lipoprotein (LDL)<3 mmol/l statins will be
      first choice, possibly with HRT additionally for its other benefits on
      cardiovascular risk factors.

PMID- 12044588
TI  - Development and preliminary validation of a silhouette satiety scale for
      children.
AB  - The purpose of this study was to determine whether young children are capable of
      using pictorial silhouettes to quantify feelings of satiety and provide
      preliminary data on the validity of this method. Subjects were 20 children, 4-6
      years old, recruited from a preschool. We hypothesized that subjects would be
      able to use the silhouettes to communicate different levels of satiety when
      imagining eating situations associated with different levels of fullness. The
      study was conducted in three stages: Stage 1 probed children's spontaneous
      definitions of hunger and fullness and identified specific eating situations they
      associated with these feelings; Stage 2 tested whether children could perform
      basic quantitative discriminations applied to food-related stimuli; Stage 3
      validated the silhouettes using an 'imagined eating situation' in which subjects
      used the silhouettes to rate how full their belly would feel in three distinct
      eating situations associated with different levels of satiety. Main results
      indicated that (1) most children readily associated the stomach with feelings of
      hunger (90%) and fullness (70%), (2) 80% of the children said they felt fullest
      after eating a meal, (3) 90-100% of the children were able to perform basic
      quantitative discriminations using food-related stimuli, and (4) children
      reported increasing feelings of satiety for situations associated with hunger,
      partial satiety, and satiety. Children were generally consistent in their ratings
      across testing sessions, although responses were less consistent for intermediary
      satiety levels. Young children may be more capable of quantitatively reporting
      feelings of satiety than is commonly believed, if appropriate experimental
      materials are used.

PMID- 12044589
TI  - Ingestion, suckling, and the problem of identity: using criteria in the
      classification of ingestive behavior.
AB  - The data reported by Nizhnikov et al. [Newborn rats first suckling experience:
      taste differentiation and suckling plasticity (2002)] do not support the authors'
      claim that they shed light on suckling mechanisms. A number of accepted criteria
      for identifying suckling are discussed in this review. The ingestion of various
      fluids through a plastic tube by neonatal or other rats does not meet any of
      these criteria. Thus, while the data reported by Nizhnikov et al. [Newborn rats
      first suckling experience: taste differentiation and suckling plasticity (2002)]
      are of interest from the perspective of infant capabilities, they do not shed
      light on the determinants of actual nipple attachment or suckling as they may
      naturally occur.

PMID- 12044590
TI  - Newborn rats' first suckling experience: taste differentiation and suckling
      plasticity.
AB  - The present study examined responsiveness of newborn rats to a surrogate nipple
      providing fluids with basic tastes (sweet, sour, bitter and salty) and assessed
      the effects of this first gustatory experience on subsequent responding to the
      nipple itself (empty nipple) or the nipple providing water. Responsiveness
      (attachment to and ingestion from a surrogate nipple providing saccharin, saline,
      quinine or ammonium chloride) was compared with that toward a nipple providing
      water. Compared to water, saline and quinine significantly reduced attachment to
      and ingestion from the nipple, while saccharin and milk significantly increased
      attachment behavior. Ammonium chloride increased attachment but not ingestive
      behavior. Suckling experience with saline, quinine and ammonium chloride
      attenuated both attachment and ingestive behaviors when subjects were tested 1 h
      later with an empty surrogate nipple or a nipple providing water. Experience with
      saccharin and milk (but not water) increased both measures. The data suggest that
      in newborn rats, as early as a few hours after birth, mechanisms of gustatory
      detection have control over suckling behavior. Initial experience with the
      tastants available from the nipple in the first suckling episode may alter
      further responsiveness to the nipple itself, mediated perhaps by mechanisms of
      appetitive and aversive conditioning.

PMID- 12044591
TI  - Cows treated with Synchromate B may cluster their sexual behaviour independent of
      follicular growth at the time of oestrus.
AB  - In order to study the relative influence of social versus hormonal influences on
      sexual behaviour, three groups were formed from a herd of 16 Brahman cows, two of
      which groups were synchronized, implanting the second group the day the first had
      the Synchromate B (SMB) withdrawn. The third group was the untreated control.
      Cows in the sexually active group (SAG) were subjected to an intensive ultrasound
      (US) schedule to monitor ovarian activity. Alternatively, US examinations and
      progesterone (P4) samples were obtained twice weekly starting one week before the
      SMB implant until one week after the last implant was removed. Twenty mounting
      series involving 13 cows were observed. All cows in Groups 1 and 2 and 50% of
      controls displayed mounting behaviour, grouped on two periods. Seven cows showed
      mounting activity on both periods (8 days apart). Three cows in Group 2 (60%)
      displayed riding behaviour when the SMB implant was in place. No differences
      (P=.39) were found between the average size of the major follicle from animals
      displaying oestrus at the expected time (6.95+/-2.6 mm), and those displaying
      oestrus outside this period in harmony with induced animals (7.79+/-1.5 mm), nor
      (P=.71) between treated (7.72+/-2.0 mm) and untreated (7.28+/-2.1 mm) cows. It is
      concluded that treated and untreated animals, and even cows with an implant in
      place, may display mounting activity concomitantly with oestrous-induced cows and
      this behaviour is not driven by follicular size at the time of the expected
      oestrus. Furthermore, the follicular development suggests that SMB treatment does
      not impede and may even enhance oestrous response in certain cows when applied
      together with exogenous estrogens.

PMID- 12044592
TI  - AP-7 into the nucleus accumbens disrupts acquisition but does not affect
      consolidation in a passive avoidance task.
AB  - The effect of the blockade of N-methyl-D-aspartic acid (NMDA)-type glutamatergic
      receptors in the nucleus accumbens septi (Acc) during different phases of a
      passive avoidance task (step-through paradigm, two chambers) of learning was
      studied in male rats which had been bilaterally cannulated into the Acc. Animals
      were trained with a punishment procedure (3 s shock of 1 mA) to avoid one of the
      chambers. The rats received either saline or (+/-)2-amino-7-phosphonoheptanoic
      acid (AP-7) solution (1 microg/1 microl) 10 min before training (pretraining
      schedule) or immediately after the shock (posttraining schedule). In the test
      phase, the animals were placed back into the white chamber after 1 and 8 days
      later. In this moment, rats stayed there for 1 min, after which the time elapsed
      between the removal of the door to the introduction into the dark chamber of the
      head (Latency 1) and body (Latency 2) and fecal boli expelled were recorded. In
      the pretraining injection schedule, the drug treatment significantly reduced
      Latency 2 (P<.05) and fecal boli (P<0.01) on Day 1, and all parameters on Day 8
      (P<.05). The posttraining injection schedule did not modify behavior. We conclude
      that a preshock NMDA-glutamatergic blockade of the Acc leads to cognitive
      disturbances during acquisition and a decrease in anxiety levels, but that the
      consolidation of a learned task is not affected by postshock administration.

PMID- 12044593
TI  - Sex differences in the acquisition of a radial maze task in the CD-1 mouse.
AB  - The purpose of the present study was to investigate spatial processing
      performance in male and female CD-1 mice. A substantial literature supports the
      existence of significant sex differences in both human and rodent models of
      learning and memory. The nature of these differences is dependent upon the
      parameters of the task, species and strain of animal. In the present study, male
      and female CD-1 mice were trained for 3 days to perform a 4/8 spatial memory task
      in an eight-arm radial maze and then tested for a total of 5 days. On the final
      day of radial maze testing, male CD-1 mice committed marginally significantly
      fewer reference memory (RM) and significantly fewer working memory (WM) errors on
      the radial maze task than female CD-1 mice. In addition, female mice obtained
      significantly fewer rewards during the final two testing sessions. The present
      data provide the first evidence for sex differences in radial maze learning in
      the CD-1 mouse, a strain known for its estrogen insensitivity. Consistent with
      the majority of literature that supports sex differences in spatial processing in
      rodents, female CD-1 mice acquired significantly fewer rewards than male CD-1
      mice during an eight-arm radial maze task.

PMID- 12044594
TI  - Effects of selective NMDA and non-NMDA blockade in the nucleus accumbens on the
      plus-maze test.
AB  - Effect of blocking N-methyl-D-aspartic acid (NMDA) and non-NMDA-glutamatergic
      receptors on performance in the plus-maze was studied in male rats bilaterally
      cannulated into the nucleus accumbens (Acc). Rats were divided into seven groups
      that received either 1 microl injections of saline, (+/-)2-amino-7
      phosphonoheptanoic acid (AP-7, 0.2, 0.5, or 1 microg) or 2,3 dioxo-6-nitro
      1,2,3,4,tetrahydrobenzo-(f)quinoxaline-7-sulphonamide disodium (NBQX, 0.2, 0.5,
      or 1 microg) 15 min before testing. Time spent in open arm, time per entry, end
      arrivals, open, closed, and total arm entries, relationship between open-, closed
      , and total arm entries, rearing, face-, head-, and body grooming, and number of
      fecal boli were recorded. Time spent in the open arm increased under AP-7 (0.5
      and 1 microg; P<.01) and NBQX (1 microg; P<.05) treatment, whereas time per entry
      was increased only with AP-7 (1 microg; P<.05). Open arm entries were increased
      by the intermediate doses of AP-7 (0.5 microg; P<.01) and NBQX (0.5 microg;
      P<.05); end arrivals were increased by the intermediate dose of AP-7 (0.5
      microg/1 microl, P<.05). The frequency of rearing, grooming, and closed arm
      entries was not affected by the treatment. We conclude that NMDA and non-NMDA
      glutamatergic blockade in the Acc lead to a behavioral disinhibition of cortical
      influences with the median doses, but that at higher doses the blockers have an
      anxiolytic-like effect.

PMID- 12044595
TI  - Individual recognition after fighting by golden hamsters: a new method.
AB  - Individual recognition is crucial for many aspects of social behavior and may be
      a specially evolved type of learning and memory. Using golden hamsters, we
      developed a behavioral method for the investigation of individual recognition.
      After a series of three brief fights, the two males were categorized as winners
      or losers. In Experiments 1 and 2, the loser was then tested in a Y-maze after
      four different intervals (30 min, 1 day, 3 days and 7 days). In Experiment 1, the
      familiar winner was confined in a stimulus compartment at the end of one arm of
      the Y, whereas no animal occupied the opposite arm. The results showed that the
      losers in the experimental group spent the most time in the base of the Y (in or
      near the start box). They also showed hesitancy to approach the winners' odors
      and spent less time near them than they spent in the same area when tested with
      no stimulus males present. In contrast, No Fight control males spent the most
      time near the stimulus males and did not hesitate in approaching them. In
      Experiment 2, losers spent less time near the odors of a familiar winner than
      control losers spent near unfamiliar winners, suggesting recognition of a
      particular winner. In Experiment 3, the losers were tested just once, 7 days
      after the last interaction. Again, they spent the most time in the base of the Y
      and avoided the arm with odors of their specific winners. These results suggest
      that losers learn to recognize individuals during brief interactions and remember
      this information for both the short term (30 min) and the long term (at least 1
      week). This behavioral method will be useful for further investigation of
      individual recognition and the neural mechanisms underlying this kind of memory.

PMID- 12044597
TI  - Odors modulate pain perception: a gender-specific effect.
AB  - Odors naturally provoke emotions that are pleasant or unpleasant. Prior studies
      have demonstrated the effects of pleasing odors on cognition and mood perception,
      but no studies have reported if they influence pain perception. In the present
      study, we measured the effect of, and relationship between, different odors on
      mood and experimental pain perception. Results show that odors significantly
      influence mood in both women and men. Compared to a neutral odor, pleasant odors
      produced a positive mood while unpleasant odors produced a negative mood.
      However, the effect of odor on pain was gender specific, as only women
      experienced the effects of odor on pain perception. Because no relationship was
      found between mood and pain perception, it could suggest that different
      mechanisms are involved in the emotional aspects of mood and pain perception.
      These results and their potential clinical implications are discussed.

PMID- 12044596
TI  - Observational analysis of feeding induced by Delta9-THC and anandamide.
AB  - Endogenous cannabinoid systems have been implicated in the physiological
      regulation of appetite by the ability of cannabinoid receptor agonists to induce
      hyperphagia. Both the exogenous cannabinoid Delta9-THC and the endocannabinoid
      arachidonoyl ethanolamide (anandamide) stimulate eating in rats. However, there
      has been no detailed analysis of the adjustments to feeding behaviour underlying
      this action. We used observational methods to determine the specific components
      of feeding affected by these compounds. Two groups (n=6) of presatiated, male,
      Lister hooded rats received either Delta9-THC (0, 0.5, 1.0 or 2.0 mg/kg) or
      anandamide (0, 1.0, 5.0 or 10.0 mg/kg sc), and their behaviour in an open field
      was recorded for 45 min. Behaviour (eating, drinking, rearing, grooming,
      sniffing, locomotion, resting/inactivity, sleeping) was continuously monitored to
      provide data on the latency, temporal distribution, duration and frequency of
      each category. Under control conditions, a minority of animals ate small
      quantities of lab chow, with feeding beginning only after a long latency. Both
      Delta9-THC and anandamide selectively stimulated feeding, with a marked reduction
      in latency. Apart from its rapid onset, cannabinoid-induced eating retained the
      normal, species-typical sequence, characteristic of untreated, free-feeding rats.
      Our data suggest that exogenously administered cannabinoids promote eating by
      increasing the incentive value of food and support a role for endocannabinoids in
      the regulation of the appetitive aspects of feeding motivation.

PMID- 12044599
TI  - Muscle jerks during behavioral sleep in a beluga whale (Delphinapterus leucas
      L.).
AB  - We conducted video recording of the behavior of one captive adult male beluga (or
      white) whale over eight nights aiming to quantify muscle jerks and to evaluate
      their relationship to the sleep-waking cycle. Presumably, the whale was asleep
      during a significant portion of the time it spent lying on the bottom of the
      pool. Individual sleep episodes lasted between 20 and 492 s and on average
      occupied 66.7+/-2.6% of the nighttime (n=8). Muscle jerks were quantified in the
      last three nights, during which an average of 144+/-24 jerks were documented per
      night. Forty-six percent of all jerks occurred within 10 s of each other. Series
      of jerks lasted 2-21 s (on average 4.8+/-0.5 s, n=97) and in total occupied 0.3
      0.7% of the rest time (0.2-0.5% of total nighttime). Jerks occurred more
      frequently at the end of rest episodes. A significant portion of rest episodes
      with jerks (62%) followed each other. These series of episodes with jerks
      alternated with periods when jerks were not recorded over 8-37 min. We conclude
      that some jerks meet the behavioral criteria of paradoxical [or rapid eye
      movement (REM)] sleep (PS). On the other hand, definitive conclusions about the
      presence and duration of this sleep stage in cetaceans cannot be reached without
      further combined electropolygraphic studies and visual observations.

PMID- 12044598
TI  - Enhancement of muscular performance by a coformulation of propionyl-L-carnitine,
      coenzyme Q10, nicotinamide, riboflavin and pantothenic acid in the rat.
AB  - A coformulation of essential factors, i.e. propionyl-L-carnitine (PLC), coenzyme
      Q10 (CoQ10), nicotinamide (NAM), riboflavin and pantothenic acid, was
      administered orally to Wistar rats for 7 weeks and its efficacy was tested
      through in vivo and in vitro techniques in improving motor functions of striated,
      cardiac and smooth musculature of the rat. In vivo experiments showed that long
      term supplementation significantly improved horizontal locomotor activity by
      about 19% in male and 26% in female rats. Maximum values of shortening velocity,
      work and power were significantly increased (P<.05) in papillary muscle isolated
      from treated rats. A positive inotropic effect was also observed on colonic
      smooth muscle strips upon treatment. Work was the most affected parameter and it
      increased by 160% in smooth muscle from treated animals. The present results
      indicate that supplementation with the combination of the above mentioned
      substances elicits positive functional changes on motor performance of skeletal,
      cardiac and smooth muscle of the rat.

PMID- 12044600
TI  - The window of opportunity for administration of magnesium therapy following focal
      brain injury is 24 h but is task dependent in the rat.
AB  - The present study was conducted to establish the window of opportunity for the
      administration of a regimen of MgCl2 pharmacotherapy following focal injury to
      the brain. Rats were subjected to unilateral electrolytic lesions of the
      sensorimotor cortex (SMC) and administered a regimen of MgCl2 (1.0 mmol/kg) or
      0.9% saline (1.0 ml/kg) beginning either 15 min, 8 h or 24 h after injury.
      Subsequent injections were administered 24 and 72 h after the initial treatment.
      Behavioral testing assessed recovery of function on several sensorimotor
      behaviors for 24 days following injury. The results of the present study suggest
      that treatment with a regimen of MgCl2 significantly facilitated recovery of
      function on the forelimb-->forelimb and vibrissae-->forelimb placing tests when
      administered 15 min, 8 h or 24 h after injury compared with saline-treated rats.
      Recovery of locomotor placing was significantly facilitated at 15 min and 8 h but
      not at 24 h compared with saline-treated rats. In addition, the ability of MgCl2
      to limit neuronal loss in the ipsilateral ventral posterior lateral (VPL) nucleus
      of the thalamus was seen at only the 15-min treatment interval. These results
      suggest that the window of opportunity for MgCl2 pharmacotherapy is 24 h, task
      dependent and is much shorter for protecting neurons in the VPL.

PMID- 12044601
TI  - The effect of social interactions on circadian self-feeding rhythms in rainbow
      trout Oncorhynchus mykiss Walbaum.
AB  - Circadian feeding rhythms have been revealed in several fish species, but whether
      or not social interactions influence the expression of the rhythms remains
      largely unexplored. This paper reported such an exploration in rainbow trout. The
      experiment was conducted in two consecutive stages in two adjacent insulated
      rooms. In Stage 1, 40 fish (146.0+/-21.7 g, mean+/-S.D.) were held individually
      in Room 1. In Stage 2, those 40 fish from Room 1 were distributed into eight
      groups of five fish according to their previous circadian properties and placed
      in Room 2. Isolated trout were generally diurnal feeders, but variability among
      the individuals was evident, with five types of diurnal self-feeding pattern
      being detected. The influence of social interactions on diel self-feeding pattern
      in a group was found to be temporary and reversible. The grouping process did not
      necessarily enhance the expression of circadian self-feeding rhythms, and the
      dominant individual(s) did not determine the properties of circadian self-feeding
      rhythms in the group.

PMID- 12044602
TI  - Heart rate and heart rate variability during a novel object test and a handling
      test in young horses.
AB  - Forty-one Dutch Warmblood immature horses were used in a study to quantify
      temperamental traits on the basis of heart rate (HR) and heart rate variability
      (HRV) measures. Half of the horses received additional training from the age of 5
      months onwards; the other half did not. Horses were tested at 9, 10, 21 and 22
      months of age in a novel object and a handling test. During the tests, mean HR
      and two heart variability indices, e.g. standard deviation of beat-to-beat
      intervals (SDRR) and root mean square of successive beat-to-beat differences
      (rMSSD), were calculated and expressed as response values to baseline measures.
      In both tests, horses showed at all ages a significant increase in mean HR and
      decrease in HRV measures, which suggests a marked shift of the balance of the
      autonomic nervous system towards a sympathetic dominance. In the novel object
      test, this shift was more pronounced in horses that had not been trained.
      Furthermore, statistical analysis showed that the increase in mean HR could not
      be entirely explained by the physical activity. The additional increase in HR,
      the nonmotor HR, was more pronounced in the untrained horses compared to the
      trained. Hence, it is suggested that this nonmotor HR might be due to the level
      of emotionality. HR variables showed consistency between years, as well as within
      the second year. These tests bring about a HR response in horses, part of which
      may indicate a higher level of emotionality; and horses show individual
      consistency of these HR variables over ages. Therefore, it is concluded that mean
      HR and HRV measures used with these tests quantify certain aspects of a horse's
      temperament.

PMID- 12044603
TI  - Behavioral responses to plant toxins by two omnivorous lizard species.
AB  - An ability to detect plant toxins and thereby avoid eating chemically defended
      plants would be very beneficial for omnivorous and herbivorous lizards. We
      studied the ability of the omnivorous Podarcis lilfordi to detect compounds
      belonging to three classes of common plant toxins, as well as responses
      indicating aversion. Solutions of the alkaloid quinine, saponin, and the phenolic
      coumarin, as well as distilled water (odorless control), were presented to
      lizards on cotton swabs. The lizards detected all three toxins as indicated by
      significantly decreased tongue-flick rates and tongue-flick attack scores in
      comparison with distilled water. Several other variables revealed aversion to
      saponin, including a low number of individuals that bit swabs, avoidance of swabs
      after tongue-flicking, performance after tongue-flicking the swab of repeated
      short-excursion tongue-flicks that were directed away from the swab and did not
      contact any substrate, failure to respond at all in the next trial, and wiping
      the snout on the floor of the terrarium. Reasons for apparent differences in
      tongue-flicking behavior between P. lilfordi and two other omnivorous lizard
      species are discussed. We also showed experimentally that saponin depresses the
      tongue-flick rate in the omnivorous Bonaire whiptail lizard, Cnemidophorus
      murinus. Tongue-flicking enables at least one lizard species to detect specific
      chemicals representing three major classes of plant toxins. It is hypothesized
      that this ability is a widespread adaptation to reduce ingestion of plant toxins.

PMID- 12044604
TI  - Social influences on cortisol and behavioral responses of preweaning,
      periadolescent, and adult guinea pigs.
AB  - In various species, the presence of an attachment figure can reduce hypothalamic
      pituitary-adrenal (HPA) responses. In the guinea pig, the mother reduces HPA
      elevations of her young both prior to and following weaning. Recently, an
      unfamiliar female was also found to reduce the HPA responses of postweaning
      guinea pigs. The present study evaluated the specificity and ontogenetic course
      of the effect of the unfamiliar female. Experiment 1 found that an unfamiliar
      adult male did not reduce the cortisol response of periadolescent subjects during
      novelty exposure. Experiment 2 showed that the effect of the unfamiliar female
      was present as early as the second week of life. Experiment 3 found that neither
      an unfamiliar adult female nor male affected the cortisol response in adult
      guinea pigs. In all experiments, the mother reduced the cortisol elevations of
      her offspring. The ability to buffer the cortisol response could not be explained
      by the amount of agonistic behavior subjects received from the stimulus animals.
      Results indicate that the mother guinea pig has a persisting ability to buffer
      HPA responses in her developing offspring; that during at least a large portion
      of the time that the mother can moderate the cortisol response of her young, so
      too can an unfamiliar adult female, but not an unfamiliar adult male; and that
      the ability of social partners to moderate HPA activity is not readily
      predictable from behavioral interactions.

PMID- 12044606
TI  - The effect of different psychological profiles and timings of stress exposure on
      humoral immune response.
AB  - The aim of this study was to analyse the effects of different timings of stress
      exposure on humoral immune response in mice previously distinguished by their own
      psychological profile. The Swiss mice were submitted to two different protocols
      of social confrontation, based on the timing of stress exposure in relation to an
      immune challenge: animals socially confronted daily for 2 weeks (SINT) and
      another group confronted daily for 3 weeks (LINT). Control groups were
      individually housed in a different room. All groups were intraperitoneally
      injected with sheep red blood cells (SRBC). The SINT group was challenged on the
      1st and 7th days of confrontation, whereas the LINT group was challenged on the
      7th and 14th days. Two days prior to the period of social conflict, the animals
      were tested in the elevated plus-maze (PM). The SINT protocol caused a more
      depressed primary immune response in the submissive mice than that observed in
      the dominants. The LINT protocol induced a marked increase in the primary immune
      response, which was more evident in the dominant mice, whilst no changes were
      observed in the secondary immune response. In the control and dominant groups,
      the correlation analysis attributed a higher anti-SRBC titre to the more anxious
      animals; by contrast, higher anti-SRBC titres were found in the less anxious
      submissive mice. These studies show that different physiological and behavioural
      adaptations to environmental demands over time, as well as different
      psychological profiles, constitute important factors to a better understanding of
      neuro-immune interactions.

PMID- 12044605
TI  - DNA fragmentation factor 45 knockout mice exhibit longer memory retention in the
      novel object recognition task compared to wild-type mice.
AB  - Apoptosis is an important process in the development and function of the central
      nervous system (CNS). To study the role of DNA fragmentation factor 45
      (DFF45/ICAD) in CNS function, we previously generated DFF45 knockout mice. We
      found that whereas they exhibit apparently normal CNS development, DFF45 knockout
      mice exhibit an increased number of granule cells in the dentate gyrus and
      enhanced spatial learning and memory compared to wild-type mice in a Morris water
      maze test. In this study, we examined the performance of the DFF45 knockout mice
      in a novel object recognition task to measure short-term nonspatial memory that
      is believed to depend on the hippocampal formation. Both wild-type and DFF45
      knockout mice exhibited novel object recognition 1 h posttraining. However,
      whereas wild-type mice no longer did so, DFF45 knockout mice were still able to
      differentiate the novel versus the familiar object 3 h posttraining. The longer
      memory retention in DFF45 knockout mice did not last up to 24 h as neither wild
      type nor DFF45 knockout mice demonstrated novel object recognition 24 h
      posttraining. These results suggest that a lack of DFF45 facilitates hippocampus
      dependent nonspatial memory, as well as hippocampus-dependent spatial memory.

PMID- 12044607
TI  - Tonin expression in the rat brain and tonin-mediated central production of
      angiotensin II.
AB  - Tonins are serine proteinases mainly found in the rat submandibular gland, which
      are capable of generating the pressor octapeptide angiotensin II (Ang II) not
      only from the classical substrate angiotensin I but also from the synthetic
      tetradecapeptide (AG(1-14)) and from angiotensinogen. In this work, tonin
      expression levels were evaluated in astrocytes and brain areas of the rat. By two
      different techniques (ribonuclease protection assay and reverse transcription
      polymerase chain reaction), we could verify the presence of tonin mRNA in
      astrocytes and in the thalamus of the rat brain. Sequencing of the amplified
      brain cDNA determined it to be identical to that found in the submandibular
      gland. Central microinjection of tonin produced a transient (10-20 min) elevation
      of blood pressure and heart rate and induced water and saline intake within the
      first 10 min after injection. Urinary volume and salt excretion increased within
      7 h after tonin injection. These effects were partially blocked by previously
      administered losartan, indicating that tonin effectively induced a central Ang II
      formation. Our data suggest that tonin may be an alternative pathway to Ang II
      generation in the brain and could participate in the physiological effects
      exerted by Ang II such as water and saline intake and blood pressure elevation.

PMID- 12044608
TI  - Gustatory responsiveness to food-associated saccharides in European rabbits,
      Oryctolagus cuniculus.
AB  - Taste preference thresholds for six food-associated saccharides and relative
      sweet-taste preferences were assessed in 12 European rabbits using two-bottle
      choice tests of brief duration (3 min). In Experiment 1, the animals were found
      to significantly prefer concentrations as low as 30 mM maltose, 50 mM polycose
      and sucrose, 75 mM glucose, 150 mM fructose, and 175 mM lactose over tap water.
      In Experiment 2, the rabbits were given a choice between all binary combinations
      of the same six saccharides presented in equimolar concentrations of 100 and 200
      mM. Preferences for individual saccharides were stable across the concentrations
      tested and indicate the following order of relative effectiveness:
      maltose=polycose>sucrose>glucose>fructose > or =lactose. The results showed
      rabbits to display a pattern of taste preference thresholds and relative taste
      preferences for food-associated saccharides similar to that found in rodents but
      differing markedly from that found in human and nonhuman primates. The results
      support the assumptions that rabbits, unlike most primates, but similar to
      rodents, may have specialized taste receptors for starch, and that the gustatory
      responsiveness of Oryctolagus cuniculus to food-associated saccharides might
      reflect an evolutionary adaptation to its dietary habits.

PMID- 12044609
TI  - Characterization and expression of the bovine growth hormone-releasing hormone
      (GHRH) receptor.
AB  - The hypothalamic hormone, growth hormone-releasing hormone (GHRH) and its
      pituitary receptor are principal regulators of pituitary growth hormone (GH)
      synthesis and release. In the present study, we cloned and sequenced a complete
      bovine pituitary GHRH receptor cDNA in order to study its expression in cattle.
      The lengths of the exons in the bovine GHRH receptor gene were determined by
      comparison of the cloned cDNA with genomic sequences obtained from a bovine
      genomic library clone. As in other species, the bovine cDNA sequence encodes a
      423-amino acid protein containing seven hydrophobic domains characteristic of a G
      protein-coupled receptor. The predicted bovine amino acid sequence shares 93, 90,
      89, 87, and 85% identity with the ovine, porcine, human, rat and mouse sequences,
      respectively. Expression of the receptor in bovine ileum, ovary, anterior
      pituitary, testis, hypothalamus, pancreas and liver was examined by RT-PCR. Of
      those tissues examined, GHRH receptor expression was detected in the anterior
      pituitary gland and hypothalamus. To gain a better understanding of GHRH receptor
      gene regulation in ruminants, we examined the effect of bovine somatotropin (bST)
      treatment on pituitary GHRH receptor expression in dairy heifers using relative
      and real-time RT-PCR. In the present study, bST treatment of dairy heifers
      resulted in no significant decline in pituitary GHRH receptor expression.

PMID- 12044611
TI  - Effect of progressive cachectic parasitism and growth hormone treatment on
      hepatic 5'-deiodinase activity in calves.
AB  - Thyroid status is compromised in a variety of acute and chronic infections.
      Conversion of thyroxine (T(4)) into the metabolically active hormone,
      triiodothyronine (T(3)), is catalyzed by 5'-deiodinase (5'D) mainly in
      extrathyroidal tissues. The objective of this study was to examine the effect of
      protozoan parasitic infection (Sarcocystis cruzi) on hepatic 5'D (type I)
      activity and plasma concentrations of T(3) and T(4) in placebo- or bovine GH
      (bGH)-injected calves. Holstein bull calves (127.5+/-2.0 kg BW) were assigned to
      control (C, ad libitum fed), infected (I, 250,000 S. cruzi sporocysts per os, ad
      libitum fed), and pair-fed (PF, non-infected, fed to intake of I treatment)
      groups placebo-injected, and three similar groups injected daily with pituitary
      derived bGH (USDA-B-1, 0.1mg/kg, i.m.) designated as C(GH), I(GH) and PF(GH). GH
      injections were initiated on day 20 post-infection (PI), 3-4 days prior to the
      onset of clinical signs of the acute phase response (APR), and were continued to
      day 56 PI at which time calves were euthanized for liver collection. Blood
      samples were collected on day 0, 28, and 55 PI. Alterations in nutritional intake
      did not affect type I 5'D in liver. Treatment with bGH increased (P<0.05) 5'D
      activity in C (24.6%) and PF (25.5%) but not in I calves. Compared to PF calves,
      infection with S. cruzi reduced 5'D activity 25% (P<0.05) and 47.8% (P<0.01) in
      placebo- and bGH-injected calves, respectively. Neither nutrition nor bGH
      treatment significantly affected plasma concentrations of T(4) and T(3) on day 28
      and 55 PI. However, plasma thyroid hormones were reduced by infection. On day 28
      PI, the average plasma concentrations of T(3) and T(4) were reduced in infected
      calves (I and I(GH)) 36.4% (P<0.01) and 29.4% (P<0.05), respectively, compared to
      pair-fed calves (PF and PF(GH)). On day 55 PI, plasma T(3) still remained lower
      (23.7%, P<0.01 versus PF) in infected calves while plasma T(4) returned to
      control values. The data suggest that parasitic infection in growing calves
      inhibits both thyroidal secretion and extrathyroidal T(4) to T(3) conversion
      during the APR. After recovery from the APR, thyroidal secretion returns to
      normal but basal and bGH-stimulated generation of T(3) in liver remains impaired.

PMID- 12044612
TI  - Castration increases pulsatile luteinizing hormone release, but fails to diminish
      mounting behavior in sexually experienced bulls.
AB  - We tested the hypothesis that mounting and chemoinvestigatory behaviors are
      testosterone-dependent in bulls. Eighteen bulls were divided into three treatment
      groups: intact (I), castrated (C) and castrated+testosterone (T). Sexual
      behaviors of all bulls were tested with an unrestrained receptive female 1 week
      prior to and weekly for 4 weeks after castration. Mounts with intromissions,
      aborted mounts and flehmen responses were quantified for each test period. In
      addition, patterns of LH and testosterone secretion were assessed at these times.
      Neither mounts with intromissions nor aborted mounts were affected by treatment.
      In contrast, numbers of flehmen responses were lower in C bulls than in the other
      groups following castration. Before castration, concentrations of LH were not
      different among groups and LH pulse frequency was approximately one pulse per
      hour. Castration resulted in a 2-fold increase in mean concentrations of LH and a
      6-fold increase in LH pulse frequency. Neither mean concentration of LH nor LH
      pulse frequency changed in I or T bulls. The data fail to support the hypothesis
      that mounting behavior is T-dependent, but supports the hypothesis that this
      steroid hormone regulates flehmen behavior in sexually experienced bulls.

PMID- 12044610
TI  - Plasma concentrations of ACTH precursors correlate with pituitary size and
      resistance to dexamethasone in dogs with pituitary-dependent
      hyperadrenocorticism.
AB  - This study was performed to determine whether in dogs with pituitary-dependent
      hyperadrenocorticism (PDH) excessive release of adrenocorticotrophic hormone
      (ACTH) is accompanied by secretion of ACTH precursor molecules. In addition, we
      investigated whether the plasma ACTH precursor concentrations were correlated
      with the size of the pituitary gland and with the degree of resistance to
      negative glucocorticoid feedback. In 72 dogs with PDH, the plasma ACTH precursor
      concentration was determined by calculating the difference between the results of
      a radioimmunoassay (RIA) in which besides ACTH, ACTH precursors were also
      measured and a highly specific immunoradiometric assay (IRMA) using a polyclonal
      antibody against ACTH. The degree of resistance to glucocorticoid feedback was
      established by determining the effect of dexamethasone administration (0.1mg/kg)
      on the urinary corticoid/creatinine ratio. The pituitary height/brain area (P/B)
      ratio, determined by computed tomography, was used as a measure for the size of
      the pituitary gland. The plasma ACTH precursors concentration ranged from 18 to
      2233ng/L (median 93ng/L). In 38 dogs, the pituitary was enlarged and plasma ACTH
      precursors concentrations in these dogs (median 130ng/L, range 24-2233ng/L) were
      significantly (P<0.05) higher than those in the dogs without pituitary
      enlargement (median 72ng/L, range 18-481ng/L). In concordance, P/B ratios
      correlated significantly with plasma ACTH precursor concentrations (r=0.35,
      P<0.01). In addition, the P/B ratios were significantly correlated with the
      degree of dexamethasone resistance (r=0.42, P<0.001). Plasma ACTH precursor
      concentrations in the dexamethasone-resistant dogs (median 210ng/L, range 24
      628ng/L) were significantly higher (P<0.01) than those in the dexamethasone
      sensitive dogs (median 72ng/L, range 18-2233ng/L). Similarly, the degree of
      dexamethasone resistance was also significantly correlated with the plasma ACTH
      precursor concentrations (r=0.33, P<0.01). Dogs with an elevated plasma alpha-MSH
      concentration (n=14) had significantly (P<0.001) higher plasma ACTH precursor
      concentrations (median 271ng/L, range 86-2233ng/L) than dogs with non-elevated
      alpha-MSH (median 73ng/L, range 18-481ng/L). In addition, the plasma
      concentrations of alpha-MSH correlated significantly with both plasma ACTH
      precursor concentrations (r=0.53, P<0.001) and P/B ratios (r=0.26, P<0.05). In
      conclusion, in all dogs with PDH the ACTH concentrations determined by the RIA
      were higher than the concentrations measured by IRMA indicating the presence of
      circulating ACTH precursors. High plasma ACTH precursor concentrations were
      especially found in dexamethasone-resistant dogs with large corticotroph
      adenomas, some of them probably of PI origin. In the association of large
      corticotroph adenoma, dexamethasone resistance and high plasma concentrations of
      ACTH precursors, the decreased sensitivity of the corticotroph cells to
      glucocorticoid feedback may play a pivotal role.

PMID- 12044613
TI  - Influence of gonadotropins on insulin- and insulin-like growth factor-I (IGF-I)
      induced steroid production by bovine granulosa cells.
AB  - To determine the effect of gonadotropins on insulin- and insulin-like growth
      factor (IGF-I)-induced bovine granulosa cell functions, granulosa cells from
      bovine ovarian follicles were cultured for 2 days in the presence of 10% fetal
      calf serum (FCS), and then cultured for an additional 2 days in serum-free medium
      with added hormones. In the presence of 0 or 1 ng/mL of insulin or IGF-I, FSH had
      little or no effect (P > 0.05) on estradiol production by granulosa cells from
      both small (1-5mm) and large (> or = 8mm) follicles. However, in the presence of
      > or = 3 ng/mL of insulin, FSH increased (P < 0.05) estradiol production by
      granulosa cells from small and large follicles such that the estimated dose
      (ED(50)) of insulin necessary to stimulate 50% of the maximum estradiol
      production was decreased by 2- to 3-fold from 22 to 28 ng/mL in the absence of
      FSH to 7-14 ng/mL in the presence of FSH. Similarly, in the presence of > or = 3
      ng/mL of IGF-I, FSH increased (P< 0.05) estradiol production by granulosa cells
      from small and large follicles such that the ED(50) of IGF-I for estradiol
      production was decreased by 4- to 5-fold from 25 to 36 ng/mL in the absence of
      FSH to 5-6 ng/mL in the presence of FSH. In the presence of FSH, the maximal
      effect of insulin on estradiol production was much greater than that of IGF-I
      (137- versus 12-fold increase) and were not additive; when combined, 100 ng/mL of
      IGF-I completely blocked the stimulatory effect of 100 ng/mL of insulin. In the
      absence of FSH, the maximal effect of insulin and IGF-I on estradiol production
      was similar. Concomitant treatment with 30 ng/mL of LH reduced (P<0.05) insulin
      stimulated estradiol production by 52% on day 1 and 19% on day 2 of treatment.
      Insulin, IGF-I and FSH also increased (P<0.05) granulosa cell numbers and
      progesterone production but their maximal effects were less (i.e., < 4-fold
      increase) than their effects on estradiol production. In conclusion, insulin and
      IGF-I synergize with FSH to directly regulate ovarian follicular function in
      cattle, particularly granulosa cell aromatase activity.

PMID- 12044614
TI  - Translational pain research: bridging the gap between basic and clinical
      research.

PMID- 12044615
TI  - Preoperative back pain is associated with diverse manifestations of central
      neuroplasticity.
AB  - Increased or decreased gain in central nervous system processing after surgery,
      i.e. neuroplasticity, may play an important role in postoperative pain.
      Identification of patient subgroups particularly vulnerable to either type of
      post-surgical neuroplasticity is thus of interest. Preoperative pain has also
      been suggested to increase vulnerability to post-surgical chronic pain
      complications due to central facilitation. To study if back pain preoperatively
      is associated with differences in central sensory processing, we measured
      transcutaneous electric sensation, pain detection and pain tolerance thresholds
      at the upper arm, lower back and lower leg in 52 consecutive patients scheduled
      for back surgery in a blinded, prospective fashion. Patients with no pain had
      significantly lower pain thresholds than patients with pain in the leg, and
      significantly higher pain thresholds than those with pain in the back. These
      results suggest that preoperative pain can induce diverse central neuroplastic
      changes, i.e. inhibition and facilitation, and that the nature of this
      neuroplasticity depends on the nature of the pain involved. The presence of
      facilitation may be the basis of the increased vulnerability described in some
      studies of patients with significant preoperative pain, whereas the implications
      of reduced pain sensitivity are less clear. The demonstration of neuroplasticity
      and its diversity are, however, likely to be of significant clinical relevance.

PMID- 12044617
TI  - Strain-dependent modification of neuropathic pain behaviour in the rat hindpaw by
      a priming painful trigeminal nerve injury.
AB  - The aim of the present study was to test the behavioural effect of infraorbital
      (IO) chronic constriction injury (CCI) on the development of neuropathic pain in
      the rat hindpaw following sciatic nerve CCI performed 7 days later. Control
      groups consisted of rats that underwent sham infraorbital surgery followed by
      sciatic CCI at identical time points. Sensory testing of the rat's face and
      hindpaw was performed at baseline and at 4, 11, 14, 17 and 21 days postoperative
      (dpo) relative to the IOCCI, at which time all rats were euthanized. To test for
      strain differences the experiment was performed on Sprague-Dawley, Sabra and
      Lewis rats. In Lewis rats the trigeminal nerve injury significantly accelerated
      the development of hindpaw mechanoallodynia (11th, 14th and 17th dpo, unpaired t
      test, P<0.05) and mechanohyperalgesia (14th and 17th dpo, unpaired t-test,
      P<0.05), following a second sciatic nerve CCI relative to the control group. This
      effect was not observed in Sprague-Dawley or Sabra rats.

PMID- 12044616
TI  - Gender, coping and the perception of pain.
AB  - Research consistently indicates that gender differences exist in pain perception,
      with females typically reporting more negative responses to pain than males. It
      also seems as if males and females use and benefit from different coping
      strategies when under stress; females seem to prefer emotion-focused coping,
      whereas males prefer sensory-focused coping. Unfortunately, experimental research
      that examines such differences in the context of pain has not yet been adequately
      investigated. The aim of the current study was, therefore, to determine whether
      gender differences would be found in the effect that sensory-focused and emotion
      focused coping instructions have on cold pressor pain experiences. Participants
      consisted of 24 male and 26 female healthy adults, all of whom reported no
      current pain. A consistent pattern of effects was found, over both behavioural
      and self-report measures of pain. Compared to females, males exhibited less
      negative pain responses when focusing on the sensory component of pain (i.e.
      increased threshold, tolerance and lower sensory pain). Furthermore, compared to
      sensory focusing, emotional focusing was found to increase the affective pain
      experience of females. Together these results confirm that important differences
      exist between men and women in the effects pain coping instructions have on the
      experience of pain. The implications of such findings for research and practice
      are discussed.

PMID- 12044618
TI  - The effect of headache pain on attention (encoding) and memory (recognition).
AB  - Memory is a key cognitive variable in pain management. This study examined the
      effect of headaches on participants' encoding of words (attention) and later
      memory for words. The dependent measures were response time during encoding and
      recognition memory; headache pain was the independent measure. Eighty
      participants were randomized to one of four groups: two groups had the same
      condition (headache pain or no headache pain) for both the encoding and memory
      tasks and two groups had mixed conditions (i.e. pain during encoding/no pain
      during recognition; no pain during encoding/pain during recognition).
      Participants with pain during encoding judged words significantly slower
      (177.53ms) than participants without pain during encoding. Participants with pain
      during the memory task recognized significantly fewer words (5.4%) than
      participants without pain during the memory task, regardless of pain condition
      during encoding. Results from this and other pain and memory studies conducted in
      this laboratory suggest that pain, as it adversely affects memory, may operate at
      a threshold level rather than on a dose-response continuum.

PMID- 12044619
TI  - Morphine responsiveness, efficacy and tolerability in patients with chronic non
      tumor associated pain - results of a double-blind placebo-controlled trial
      (MONTAS).
AB  - Efficacy, long-term effectiveness and safety of opioids in chronic non-tumor
      associated pain syndromes (NTAS) are still under debate. The study (MONTAS) was
      performed by physicians and psychologists as a multicenter prospective,
      randomized, double-blind placebo-controlled crossover trial, followed by an open
      long-term study. Patients were enrolled only when pain relief from specific
      defined pretreatment was insufficient. Patients were randomly assigned to group I
      receiving sustained-release morphine (doses: 20mg/d titrated appropriately to a
      maximum of 180mg/d) in the first week, placebo in the second week or group II
      receiving study medication in reverse order. The primary endpoint was defined as:
      (i) adequate pain relief (pain intensity of less than 50% of pretreatment
      intensity or less than 5 on a 11 point Numerical Rating Scale) and (ii) pain
      rated as tolerable and (iii) adverse effects rated as tolerable. Full responders
      (all criteria fulfilled under morphine) and partial responders (less pain relief,
      but tolerable side effects) were offered continuation of treatment with oral
      morphine in an open long-term study (LAMONTAS), to be published later. Forty-nine
      patients of 997 patients screened fulfilled the inclusion criteria for MONTAS and
      were enrolled. Mean pain intensity in all patients was reduced by morphine from
      7.8 to 5.2 (NNT: 2.2); in 17 (35.4%) responders from 7.4 to 2.9, in 17 (35.4%)
      partial responders from 7.8 to 5.6 and in 14 (29.2%) non-responders from 8.2 to
      7.7. Pain reduction correlated with improvement of physical function. Pain
      disability, depression score, mood and exercise endurance improved, particularly
      in responders. Gastrointestinal complaints increased, central nervous system
      related complaints were reduced. Efficacy and safety of morphine in NTAS were
      demonstrated in this randomized-controlled trial. Pretreatment failure was the
      indication for trying morphine treatment; predictive factors for responsiveness
      could not be identified.

PMID- 12044620
TI  - Psychophysical analysis of visceral and cutaneous pain in human subjects.
AB  - Clinical evidence suggests that cutaneous and visceral pain differ in sensory,
      affective, and motivational realms, yet there has been little comparative
      characterization of these types of pain. This study uses psychophysical measures
      to compare directly visceral and cutaneous pain and sensitivity. Healthy subjects
      (10 males, seven females, age 19-29) evaluated perceptions evoked by balloon
      distention of the distal esophagus and contact heat on the upper chest. Subjects
      gave continuous ratings of pain intensity using an on-line visual analog scale
      (VAS), reported maximum pain intensity and unpleasantness on printed VASs, chose
      phrases from the McGill Pain Questionnaire and Spielberger State-Trait Anxiety
      Inventory, and drew the area of perceived sensation. For esophageal distention,
      the threshold for pain intensity was higher than that observed for
      unpleasantness, whereas for contact heat, pain and unpleasantness thresholds did
      not differ for either phasic (10s) or tonic (36s) stimulus application. The
      relative unpleasantness, calculated as the difference between the unpleasantness
      and the intensity ratings, was higher during esophageal distention than during
      either phasic or tonic cutaneous heat; this difference in relative unpleasantness
      was seen at all intensities of esophageal stimulation. Subjects chose
      significantly more affective words and reported more anxiety during visceral pain
      than during phasic cutaneous heat pain. A similar tendency was observed when
      visceral pain was compared to tonic cutaneous heat pain. Subjects also chose a
      wider range of words to describe visceral than cutaneous pain. On-line VAS
      ratings revealed greater pain sensation after stimulus termination during
      visceral than during phasic cutaneous pain; likewise, a similar tendency was
      observed between visceral and tonic cutaneous pain. Finally, visceral pain led to
      a more spatially diffuse sensation and was referred to the entire chest and
      sometimes to the back. Our results show that visceral pain is more unpleasant,
      diffuse, and variable than cutaneous pain of similar intensity, independent of
      the duration of the presented stimuli. The data suggest the likelihood of both
      similarities and differences in the neural substrates underlying visceral and
      cutaneous pain.

PMID- 12044621
TI  - Pharmacological treatments for acute migraine: quantitative systematic review.
AB  - We wanted to compare the analgesic efficacy and adverse effects of
      pharmacological treatments for acute migraine through a systematic review of
      randomised controlled trials in patients with acute migraine pain of moderate to
      severe intensity. Trials were identified from systematic searching of
      bibliographic databases. For eletriptan information from all trials was supplied
      by Pfizer Inc. Outcomes sought were headache relief at 1 and 2h, patients pain
      free at 2h and sustained relief over 24h for treatments compared with placebo.
      Numbers-needed-to-treat (NNTs) were calculated, together with relative benefit.
      Information on adverse effects was also collected. Comparisons of relative
      efficacy used the same definition of headache, the same degree of pain at the
      start of treatment and the same definitions of outcomes, and always compared with
      placebo. Forty-eight publications reporting on 54 trials were included in the
      meta-analyses, with 79 placebo comparisons for the primary outcome of headache
      relief at 2h. Information on any outcome was available for nine oral medications,
      two intranasal medications and subcutaneous sumatriptan in 21,022 patients. For
      headache relief at 2h NNTs ranged from 2.0 for subcutaneous sumatriptan 6mg to
      5.4 for naratriptan 2.5mg. For patients pain free at 2h NNTs ranged from 2.1 for
      subcutaneous sumatriptan 6mg to 8.6 for aspirin 900mg plus metoclopramide 10mg.
      For sustained relief over 24h NNTs ranged from 2.8 for eletriptan 80mg to 8.3 for
      rizatriptan 5mg. It was not possible to systematically review adverse effects
      data. Most interventions are effective. There is considerable information on
      relative efficacy for a number of outcomes.

PMID- 12044622
TI  - ATP can enhance the proton-induced CGRP release through P2Y receptors and
      secondary PGE(2) release in isolated rat dura mater.
AB  - Trigeminal afferent neurons express ionotropic P2X receptors for extracellular
      ATP which are known to be sensitive to low interstitial pH. Both conditions - ATP
      release and tissue acidosis - may occur in the dura following the ischemia phase
      of migraine attacks. Aim of this study was to investigate whether and how ATP and
      protons may cooperate in exciting meningeal afferents. After removal of the
      cerebral hemispheres hemisected scull cavities of adult Wistar rats were used as
      organ bath of their own lining, the dura mater. The dura was chemically
      stimulated and the amounts of immunoreactive calcitonin gene-related peptide
      (iCGRP) and prostaglandin E(2) (PGE(2)) released into incubation fluid were
      measured using enzyme immunoassays. Stimulation with ATP (10(-4) and 10(-3)M)
      augmented iPGE(2) release dose-dependently whereas iCGRP secretion was minimally
      enhanced only if the dura had previously been depleted of extracellular ATP using
      hexokinase. Acid buffer solutions (pH 5.9 and 5.4) resulted in pH-dependent
      increase of iCGRP release but reduced iPGE(2) release. Purines (ATP 10(-3)>UTP
      10(-4)M>ATP 10(-4)M) and PGE(2) (10(-5)M) were found to facilitate the proton
      induced increase in iCGRP release. The proton-reduction of PGE(2) release was
      overcome by adding ATP (10(-3)M). S(+)-flurbiprofen (10(-6)M) suppressed both the
      basal and stimulated iPGE(2) release and prevented the ATP(10(-4)M)-induced
      facilitation of the proton response. The facilitating effect of ATP was also
      blocked under suramin, a non-selective P2 antagonist, and under reactive blue, an
      non-selective P2Y-antagonist, but not under pyridoxalphosphate-6-azophenyl-2',4'
      disulphonic acid, a P2X-antagonist. The present results provide evidence that ATP
      has poor, if at all, direct excitatory effects on CGRP-containing trigeminal
      nerve endings in the isolated dura and its facilitatory action seems to depend on
      G-protein coupled P2Y receptors and secondary PGE(2) release. The UTP effect and
      the antagonist profile is indicative for the P2Y(2) receptor subtype.

PMID- 12044624
TI  - A single infusion of intravenous ketamine improves pain relief in patients with
      critical limb ischaemia: results of a double blind randomised controlled trial.
AB  - We report the first double blind randomised controlled trial of regular opioids
      and an infusion of low dose (0.6 mg/kg) intravenous ketamine compared with
      opioids and placebo in patients with allodynia, hyperalgesia and hyperpathia
      secondary to critical limb ischaemia. Thirty-five patients completed the study,
      18 received regular opioids plus ketamine, while 17 received regular opioids plus
      placebo. Using the Brief Pain Inventory, the % pain relief that the patients in
      the ketamine group attributed to their medication improved significantly from 50%
      immediately pre-infusion to 65% 24 h post-infusion and 69% 5 days post infusion.
      Over the same period, the pain relief achieved by the placebo group rose from 58%
      pre-infusion to 56% 24 h post infusion and then 50% relief 5 days later. This was
      statistically significant (P<0.05) using both the t-test and the Wilcoxon Rank
      Sum test. The ketamine group also showed a statistically significant difference
      24 h post infusion of the effect of pain on their general activity (P=0.03) and
      on their enjoyment of life (P=0.004). This study shows that combining a single
      infusion of low dose ketamine with regular opioid analgesia can result in a
      significant improvement in pain relief for this patient group.

PMID- 12044623
TI  - Continual systemic infusion of lidocaine provides analgesia in an animal model of
      neuropathic pain.
AB  - We examined whether continual constant-rate infusion of lidocaine would provide
      analgesia during the initial post-injury phase in the chronic constriction injury
      model of neuropathic pain. Male Sprague-Dawley rats were divided into control and
      ligated groups and infused with saline or lidocaine (0.15, 0.33, 0.67, and
      1.3mg/kg/h) via subcutaneously implanted Alzet((R)) osmotic minipumps. Thermal
      withdrawal latencies were obtained prior (Day 0) and 3 days after loose sciatic
      ligation and pump implantation surgery. Ligated animals receiving lidocaine at
      0.67 or 1.3mg/kg/h exhibited no change in withdrawal latency on Day 3 after
      surgery, indicating that lidocaine at these doses prevented the development of
      thermal hyperalgesia as a sign of neuropathic pain. In contrast, ligated animals
      treated with saline or lidocaine at 0.15 or 0.33mg/kg/h exhibited hyperalgesia on
      Day 3 after surgery, indicating that these lower doses of lidocaine failed to
      provide analgesia. Control animals treated with saline or any of the lidocaine
      doses exhibited no change in withdrawal latencies between Day 0 and Day 3. In a
      separate group of ligated animals, lidocaine infusion (0.67mg/kg/h) that was
      started 24h after sciatic ligation surgery reversed the already present thermal
      hyperalgesia. Average plasma lidocaine concentrations were 0.11, 0.36, and
      0.45microg/ml for animals receiving 0.33, 0.67 and 1.3mg/kg/h of lidocaine,
      respectively. These results suggest that continual systemic infusion of lidocaine
      prevents or reverses the development of neuropathic pain following chronic
      constriction injury. These results add to the increasing body of evidence
      supporting the therapeutic value of preemptive and post-operative lidocaine
      administration for the relief of neuropathic pain.

PMID- 12044625
TI  - Ethanol consumption patterns and conditioned place preference in mice lacking
      preproenkephalin.
AB  - There is a great deal of evidence suggesting that endogenous opioid systems are
      involved in the control of ethanol-seeking behavior and reward. To ascertain the
      role of the enkephalinergic opioid peptide system in these processes, we examined
      voluntary ethanol consumption patterns in mice lacking the preproenkephalin
      (Penk) gene using a two-bottle choice paradigm with free access to water and
      increasing concentrations of ethanol (2, 4, 8, and 10% v/v). We also examined the
      ability of ethanol (2 g/kg i.p.) to establish a conditioned place preference in
      these mice. No differences in ethanol consumption or preference were observed
      between wildtypes and Penk null mutant mice. In addition, both genotypes
      displayed a similar conditioned place preference to ethanol. These data suggest
      that the preproenkephalin system is not involved in voluntary ethanol consumption
      patterns or ethanol reward.

PMID- 12044626
TI  - Dissociation in the effects of the D2/D3 dopaminergic agonist quinpirole on
      drinking and on vasopressin levels in the rat.
AB  - In the present study, we investigated the role of vasopressin in the development
      of quinpirole-induced hyperdipsia in the rat. We report that: (1), an acute
      intraperitoneal (i.p.) injection of 0.56 mg/kg of quinpirole increased plasma
      vasopressin (radioimmunoassay) at 15 min but not at 30 or 120 min; (2), nine
      daily injections of quinpirole (0.56 mg/kg, i.p.) progressively increased water
      intake and diuresis for a period of several hours after each treatment; (3),
      quinpirole hyperdipsia was associated with apparently normal levels of
      vasopressin (which might be considered inappropriately high in the presence of
      excessive drinking); (4), quinpirole reduced vasopressin and oxytocin, but not
      angiotensin, immunoreactivity in the supraoptic nucleus. These findings suggest
      that quinpirole hyperdipsia is a sound animal model of psychotic polydipsia.

PMID- 12044627
TI  - Localization of cAMP-dependent protein kinase in the actin and microtubule
      cytoskeletons in mouse hippocampal neurons.
AB  - Cyclic adenosine monophosphate-dependent protein kinase (PKA) is involved in
      various biological functions in neurons. To investigate the subcellular
      localization of PKA, we stained cultured hippocampal neurons with anti-PKA
      catalytic subunit antisera. PKA catalytic subunit colocalized with microtubules
      (MTs) in dendrites as well as with the actin filaments (F-actin) in growth cones.
      After treatment with cytochalasin B, the colocalization of PKA catalytic subunits
      with MTs was enhanced, whereas the colocalization with F-actin was suppressed.
      This result indicates that PKA is anchored to the actin and MT cytoskeletons, and
      disruption of F-actin releases PKA to the cytoplasm, which then leads to an
      increase in the amount of PKA in MT domains in the neuron.

PMID- 12044629
TI  - Adaptation of the circadian rhythm of 6-sulphatoxymelatonin to a shift schedule
      of seven nights followed by seven days in offshore oil installation workers.
AB  - This study evaluated circadian adaptation in a 'swing shift' schedule (seven
      nights, 18:00-06:00 h; then 7 days, 06:00-18:00 h) on North Sea oil
      installations. Eleven healthy men provided sequential urine collections for the
      study period offshore. The urinary melatonin metabolite 6-sulphatoxymelatonin
      (aMT6s) was used as an index of circadian phase. A significant difference
      (P=0.0004) was found between the mean aMT6s acrophase (calculated peak time) at
      the start (+/-SD: 05:34+/-2.42 h) and end (+/-SD: 10.95+/-3.34 h) of the night
      shift week, but not between the start (+/-SD: 11:04+/-4.03 h) and end (+/-SD:
      12:59+/-8.83 h) of the day shift week. As a group, the subjects adapted to the
      night shift but very large individual variations were seen during the day shift.
      These individual differences clearly require further study.

PMID- 12044628
TI  - Confirmation of association between D10S583 and Alzheimer's disease in a case-
      control sample.
AB  - Several independent studies have reported that loci on chromosome 10 are
      associated/linked with Alzheimer's disease (AD), including a family-based study
      demonstrating an association between the marker D10S583 and AD. We have examined
      the D10S583 polymorphic marker and apolipoprotein E (APOE) gene in a case-control
      study. We observed the expected association of the APOE allele varepsilon4 with
      AD, and an inverse association between the D10S583 allele 209 and AD. These data
      support the original findings that suggest the presence of a candidate gene for
      AD in this region of chromosome 10. The nearby insulin degrading enzyme gene has
      been previously proposed as a candidate gene; however, a number of other putative
      candidate genes are also located in this region. The ongoing investigation of the
      genetic source of association and linkage in this region is clearly warranted.

PMID- 12044630
TI  - Ethanol induces rapid lipid peroxidation and activation of nuclear factor-kappa B
      in cerebral vascular smooth muscle: relation to alcohol-induced brain injury in
      rats.
AB  - The present study was designed to test the hypothesis that acute administration
      of alcohol (ethanol) to primary cultured cerebral vascular smooth muscle cells
      will cause lipid peroxidation, inhibition of IkappaB phosphorylation, and
      inhibition of nuclear transcription factor-kappa B (NF-kappaB). Ethanol (10, 25,
      100 mM) resulted in concentration-dependent rises in malondialdehyde in as little
      as 30-45 min after exposure to the alcohol, rising to levels 2.5-10x normal after
      18-24 h. Using EMSA assays and specific antibodies, ethanol caused three DNA
      binding proteins (p50, p65, c-Rel) to rise in nuclear extracts in a concentration
      dependent manner. Using a rabbit antibody, IkappaB phosphorylation (and
      degradation) was stimulated by ethanol (in a concentration-dependent manner) and
      inhibited by a low concentration of the NF-kappaB inhibitor, pyrrolidine
      dithiocarbamate. These new biochemical and molecular data indicate that ethanol,
      even in physiologic concentrations, can elicit rapid lipid peroxidation and
      activation of NF-kappaB in cerebral vascular muscle cells. The present results
      when viewed in light of other recently published data suggest that ethanol
      induced lipid peroxidation and activation of nuclear transcription factors
      probably play important roles in alcohol-induced brain-vascular damage,
      neurobehavioral actions and stroke.

PMID- 12044631
TI  - Early detection of cognitive impairment in patients with obstructive sleep apnea
      syndrome: an event-related potential study.
AB  - Event-related potentials (ERPs) were recorded to visual stimuli in a task that
      required matching the shape and serial position of the probes against previously
      memorized items. The effects of hypoxia on ERP were investigated in 24 patients
      with obstructive sleep apnea syndrome (OSAS) and a matched control group. N2b
      late positive-going (LPC) components were elicited by probes that identically
      matched the memorized items (no-conflict condition). In contrast, N270-LPC and
      N270-N430-LPC components were elicited by probes having low-conflict and high
      conflict with the memory set. Conflict ERP effect decreased in mild, while both
      no-conflict and conflict ERP effects decreased in amplitude in severe OSAS
      patients. Conflict ERPs associated with processing of conflicting information are
      more vulnerable than no-conflict ERPs to hypoxic cerebral damage.

PMID- 12044633
TI  - Knockdown of spinal opioid receptors by antisense targeting beta-arrestin reduces
      morphine tolerance and allodynia in rat.
AB  - The development of morphine tolerance and sciatic nerve injury-induced allodynia
      after functional knockdown of spinal opioid receptors using antisense
      oligonucleotides targeting beta-arrestin was investigated. Ineffectiveness of
      morphine in neuropathic pain suggests an implication of the same mechanism in
      these two processes. The development of morphine tolerance (10 microg
      intrathecally (i.th.), every 12 h) was significantly inhibited in rats, which
      received i.th. beta-arrestin antisenses (2 nM). Acute and chronic (6 days) i.th.
      administration of antisenses antagonized the allodynia in the rat model of
      neuropathic pain. Our results demonstrated that i.th. administration of beta
      arrestin antisenses delayed development of tolerance to morphine and nerve injury
      induced cold allodynia, which suggest that both of the investigated phenomena may
      be mediated by a similar mechanism, e.g. receptor desensitization. Moreover, the
      antisense oligonucleotides targeting beta-arrestin may constitute a new approach
      to the therapy of neuropathic pain.

PMID- 12044632
TI  - Interaction of a new potent anticholinesterasic compound (+/-)huprine X with
      muscarinic receptors in rat brain.
AB  - The interaction of rac-12-amine-3-clor-6,7,10,11-tetrahydro-9-ethyl-7-11
      methanecyclo-octane[b]quinoline ((+/-)huprine X) with M(1) and M(2) receptors has
      been studied in rat brain. Specific binding of [(3)H]pirenzepine or
      [(3)H]quinuclinidylbenzylate to hippocampus preparations was inhibited by (+/
      )huprine X. This drug displayed a greater affinity for M(1) (K(i)=0.338+/-0.41
      microM) than M(2) (K(i)=4.66+/-0.32 microM) receptors. In functional studies, (+/
      )huprine X (1 microM) increased the release of [(3)H]dopamine in cortical
      synaptosomes, and this effect was partially reverted by atropine and
      mecamylamine, suggesting an agonistic effect on both M(1) and nicotinic
      receptors. The inhibitory effect of (+/-)huprine X (10 microM) on
      [(3)H]acetylcholine release and the subsequent reversion by atropine suggests
      that the drug also has an agonist effect on M(2) receptors. The present results
      demonstrate that this acetylcholinesterase inhibitor has an ample cholinergic
      profile, which suggests a potential source of interest of (+/-)huprine X in
      Alzheimer's disease therapy.

PMID- 12044635
TI  - Transient forebrain ischemia induces expression of serine/threonine protein
      phosphatase 1 mRNA in the vulnerable regions of gerbil brain.
AB  - Apoptosis is thought to be implicated in delayed neuronal cell death following
      transient forebrain ischemia. Recently, apoptosis in neurons induced by an
      inhibitor of serine/threonine (ser/thr) protein phosphatases (PPs) has been
      reported. In this study, we investigated the effect of transient forebrain
      ischemia on the expression of ser/thr PPs in the brain of Mongolian gerbils. At
      24 h after 5-min bilateral carotid artery occlusion, Northern blotting analysis
      revealed the increase of PP1 mRNA expression in the vulnerable CA1 region of the
      hippocampus and striatum, but not in the cortex and CA3 region. In contrast, the
      protein level of PP1 detected by Western blotting analysis decreased in all
      regions. We conclude that the inhibition in PPs expression in the vulnerable
      regions may affect cell death after transient forebrain ischemia.

PMID- 12044634
TI  - Reversible and irreversible components of [(3)H]-N-propylnorapomorphine
      interaction with rat striatal membranes.
AB  - The kinetics of L-(-)-[N-propyl-(3)H(N)]-norapomorphine ([(3)H]NPA) interactions
      with rat striatal membranes were studied. The analysis revealed that in addition
      to specific dopaminergic binding a substantial part of the radioligand was bound
      irreversibly to heterogeneous populations of non-specific binding sites of these
      membranes. The specific binding of [(3)H]NPA with dopamine receptors, determined
      from the differences of kinetic curves of total and non-specific binding, was
      fast, reversible, and revealed high affinity. The irreversible component was
      heterogeneous and seems to be related to oxidative degradation of the
      radioligand, as the rate of this process was substantially reduced by
      antioxidants like ascorbic acid and dithiothreitol.

PMID- 12044636
TI  - Analysis of synphilin-1 and synuclein interactions by yeast two-hybrid beta
      galactosidase liquid assay.
AB  - Synphilin-1 interacts with alpha-synuclein, which has been implicated in the
      pathogenesis of Parkinson's disease (PD). By examination of their interactions
      quantitatively, with the use of the yeast two-hybrid beta-galactosidase assay, we
      find that the synuclein amino acid (aa) 1-65 region is sufficient for an
      interaction. A central domain of synphilin-1, aa 349-555, is both necessary and
      sufficient for an interaction with alpha-synuclein. We did not observe an effect
      of the synuclein A53T mutation, which causes one familial form of PD, on
      interactions with synphilin-1. However, the A30P mutation caused an increase in
      the interaction between the synuclein aa 1-65 fragment and the synphilin-1
      central domain.

PMID- 12044637
TI  - Resistance to striatal dopamine depletion induced by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine in mice expressing human mutant Cu,Zn superoxide dismutase.
AB  - Recent data indicate that overexpression of the enzyme Cu,Zn superoxide dismutase
      (SOD1) in mice confers neuroprotection against various dopamine neurotoxins like
      1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine, 6
      hydroxydopamine and methylenedioxymethamphetamine. In the present study we
      investigated whether a mutant form of SOD1 (G93A), occurring in humans affected
      by amyotrophic lateral sclerosis, leads to a differential vulnerability of
      nigrostriatal dopaminergic neurons to the chronic dopamine depletion induced by
      the selective neurotoxin MPTP. Our results indicate that overexpression of both
      wild-type and human mutant SOD1 induces comparable neuroprotective effects
      against striatal dopaminergic depletion.

PMID- 12044639
TI  - Caudal ventrolateral medulla mediates the depressor response elicited by the
      greater splanchnic nerve afferent stimulation in rats.
AB  - Caudal ventrolateral medulla (CVLM) plays an important role in the regulation of
      reflex cardiovascular activity. In the present study, the possible involvement of
      the CVLM in mediating the depressor response elicited by the greater splanchnic
      nerve (GSPL) afferent stimulation was explored in rats anesthetized with urethane
      and alpha-chloralose. Microinjection of lidocaine, and the glutamate receptor
      antagonists, kynurenic acid and 2-amino-7-phosphonolieptanoic acid, into the CVLM
      significantly blocked the depressor response induced by the GSPL afferent
      stimulation. Electrical stimulation of the GSPL inputs excited 48 of 75 CVLM
      neurons tested (64%). Sixteen out of 21 excited CVLM neurons tested received
      baroreceptor inputs. Coherence analysis revealed a strong cardiac-related rhythm
      in the discharges of 11 out of these 21 excited neurons. These results suggest
      the involvement of CVLM neurons and activation of glutamate receptors in the CVLM
      in mediating the depressor response induced by the GSPL afferent stimulation in
      rats.

PMID- 12044638
TI  - Protective effect of ginsenosides, active ingredients of Panax ginseng, on kainic
      acid-induced neurotoxicity in rat hippocampus.
AB  - Ginsenosides are known to attenuate glutamate-induced cell injuries in vitro. We
      investigated the in vivo effect of ginsenosides on kainic acid (KA)-induced
      neurotoxicity in rat hippocampus using the methods of acid fuchsin (AF) staining
      and heat-shock protein-70 (HSP-70) immunoreactivity to detect neuronal death and
      stress, respectively. Pretreatment of ginsenosides (50 or 100 mg/kg for 7 days)
      via intraperitoneal (i.p.) administration significantly attenuated KA (10 mg/kg
      i.p.)-induced cell death by decreasing AF-positive neurons in both CA1 and CA3
      regions of rat hippocampus compared with KA treatment alone. Pretreatment of
      ginsenosides (50 or 100 mg/kg for 7 days) via i.p. administration also
      significantly suppressed KA-induced induction of HSP-70 in both regions of rat
      hippocampus. These results show that ginsenosides are effective in protecting
      hippocampal CA1 and CA3 cells against KA-induced neurotoxicity.

PMID- 12044640
TI  - Are stance ankle plantar flexor muscles necessary to generate propulsive force
      during human gait initiation?
AB  - The study examined whether the generation of the forward propulsive force (PF)
      during gait initiation resulted mainly from the electromyogram activity of stance
      ankle plantar flexor muscles (APF) which 'push' on the ground as is generally
      claimed in the literature. Six unilateral above-knee amputees performed a
      specific gait initiation protocol, i.e. they were asked to walk as fast as
      possible from an upright posture. Data from a force platform were collected and
      processed to obtain gait parameters (centre of mass (CoM) acceleration,
      anteroposterior (A/P) progression velocity, step length, etc.). The results
      showed that the A/P CoM velocity at the time of foot-off differed depending on
      the state of the lower limb (sound or prosthetic limb) performing the step.
      However, the A/P velocity of the CoM reached at the time of foot contact was
      similar whatever the state of the lower limb initiating the gait. Thus, the
      absence of ankle and knee muscles did not affect the velocity of body
      progression, i.e. the generation of the PF in gait initiation. Furthermore, the
      comparable slopes of the A/P velocity between the stance sound limb and the
      stance prosthetic limb suggest that the organization of the motor synergy
      underlying the production of the PF remained the same and did not directly
      involve the APF. However, other mechanisms could explain PF generation. PF could
      be generated by the swing leg oscillation, by the trunk movement, or by other
      mechanisms such as the energy transfer and the exchange of gravity potential
      energy into kinetic energy.

PMID- 12044642
TI  - Chronotropic response of beta-adrenergic-, muscarinic-, and calcitonin gene
      related peptide-receptor agonists in right atria from neonatal capsaicin-treated
      rats.
AB  - We evaluated the potency of isoproterenol, carbachol, pilocarpine and calcitonin
      gene-related peptide (CGRP) in the rat right atria at 30, 60 and 90 days after
      neonatal capsaicin treatment. Neonatal rats were pretreated on the second day of
      life with capsaicin (50 mg/kg). The capsaicin pretreatment caused a five-fold
      rightward shift at the pEC(50) level on the concentration-response curves to
      isoproterenol in 30-day-old rats. Propranolol (10 mg/kg, given 15 min prior to
      capsaicin treatment) prevented this subsensitivity. No changes in the potency of
      isoproterenol were observed at 60 and 90 days after capsaicin pretreatment. The
      potency and maximal responses of CGRP in the right atria in 30-day-old rats were
      significantly higher than in 60- and 90-day-old rats; however, no differences
      were found between control and capsaicin groups. The potency and maximal
      responses to carbachol and pilocarpine were not changed in all groups. The
      neonatal capsaicin treatment reduced by about 74% the CGRP content in the heart
      in all groups. In summary, capsaicin treatment in newborn rats produces a
      desensitization of chronotropic response mediated by beta-adrenoceptors in
      isolated right atria from 30-day-old rats possibly due to a massive release of
      catecholamines.

PMID- 12044641
TI  - Electrophysiological localization of the subthalamic nucleus in parkinsonian
      patients.
AB  - Deep brain stimulation of the subthalamic nucleus (STN) is becoming the procedure
      of choice to reduce symptoms of Parkinson's disease such as rigidity, akinesia
      and tremor. We present here a series of electrophysiological recordings performed
      in 34 patients along a standardized electrode trajectory. Neuronal activity along
      the trajectory consists of a first heterogeneous population of thalamic cells
      with a mean frequency of 24.8+/-1.4 Hz followed by a silent zone and a second
      population of STN neurones with a significantly higher spiking frequency
      (P<0.001) of 42.3+/-1.8 Hz. This study confirms previous findings and suggests
      that rapid measurement of neuronal spiking frequency and burst index is
      sufficient to determine precisely the vertical position of the STN.

PMID- 12044643
TI  - Vasoactive intestinal peptide attenuates cytochrome c translocation, and
      apoptosis, in rat hippocampal stem cells.
AB  - While widely distributed in the brain, one area with concentrated levels of
      vasoactive intestinal peptide (VIP) is the hippocampus. In this study, rat
      hippocampal stem cells were used to examine VIP's effects on apoptotic cell death
      induced by withdrawal of trophic support. In the apoptotic cascade, the
      translocation of cytochrome c from the mitochondria to the cytoplasm activates
      caspases, resulting in cell death. VIP decreased this translocation of cytochrome
      c in a dose-dependent manner, and reduced apoptosis. This demonstrates that VIP
      regulates neuronal apoptosis and may contribute to stem cell homeostasis.

PMID- 12044645
TI  - Sex differences in the incidence of total callosal agenesis in BALB/cCF mice.
AB  - Corpus callosum (CC) development and adult morphology seems to be affected by
      sex. Here we analyzed the incidence of total callosal agenesis in 341 adult male
      and 318 female BALB/cCF mice. This strain of mice presents total or partial
      callosal agenesis in approximately 20-30% of its population. No significant
      differences were found in overall distributions of CC lengths and in average
      callosal lengths (totally acallosal excluded) between male and female mice.
      However, a highly significant difference in the incidence of total callosal
      agenesis was demonstrated: 18% (n=56) of the female mice presented such trait as
      opposed to 10% of males (n=34). This last result suggests that sex is a relevant
      factor in callosal development in its earliest stages of formation.

PMID- 12044644
TI  - Release of gamma-[(3)H]aminobutyric acid in rat brain cortical slices by alpha
      scorpion toxin.
AB  - In this paper, the effect of the alpha-scorpion toxin tityustoxin (TsTX) in the
      release of gamma-[(3)H]aminobutyric acid ([(3)H]GABA) from rat brain cortical
      slices is described. The TsTX-stimulatory effect on the release of [(3)H]GABA was
      dependent on incubation time and TsTX concentration, having an EC(50) of 0.33
      microM. Tetrodotoxin (TTX) completely inhibited the TsTX action on [(3)H]GABA
      release. The scorpion toxin effect was calcium-dependent and involves P/Q calcium
      channels. beta-Alanine also induces the release of [(3)H]GABA that was not
      inhibited by TTX but was additive in the presence of TsTX. The data suggest a
      neuronal origin for the release of [(3)H]GABA by TsTX.

PMID- 12044646
TI  - Gaze direction affects face perception in humans.
AB  - We recorded event-related potentials (ERP) in response to images of faces with a
      straight gaze (straight eyes) and eyes averted (averted eyes). Peak latencies of
      ERP components showed no significant change between straight eyes and averted
      eyes, but amplitude for averted eyes, particularly when averted to the right, was
      significantly larger than that for straight eyes at the lateral temporal
      electrode of the right hemisphere. Single-unit recordings in monkeys and
      neuroimaging studies in humans have revealed activity in the lateral temporal
      region, mainly the superior temporal sulcus, and a clinical study demonstrated
      the importance of the right hemisphere when viewing gaze direction. This is the
      first systematic neurophysiological report to confirm these findings using ERP.

PMID- 12044647
TI  - Functional role of the preoptic area and anterior hypothalamus in
      thermoregulation in freely moving rats.
AB  - We recently reported that perfusion of tetrodotoxin (TTX) into the preoptic area
      and anterior hypothalamus (PO/AH), by using a microdialysis technique, induced an
      increase in body temperature (Tb) under normal and hot ambient temperatures (23
      and 35 degrees C) in freely moving rats. However, the procedure had no effect on
      Tb under a cold ambient temperature (5 degrees C). The present study was designed
      to determine the mechanism(s) of increases in Tb after perfusion of TTX into the
      PO/AH, by measuring tail skin temperature (Ttail) as an index of heat loss, and
      heart rate (HR) and locomotor activity (Act) as indexes of heat production, under
      three ambient temperatures. Under normal ambient temperature (23 degrees C),
      perfusion of TTX induced significant hyperthermia with increased HR, Act and
      Ttail. In a hot environment (35 degrees C), perfusion of TTX induced a greater
      increase in Tb with increased HR but no change in Ttail and Act. In a cold
      environment (5 degrees C), perfusion of TTX had no effect on Tb with a slight
      increase in Act but no change in HR and Ttail. Our results suggest that the PO/AH
      may be involved in inhibition of heat production and excitation/inhibition of the
      tail vasomotor tone.

PMID- 12044648
TI  - Changes in the distribution and density of caveolin 3 molecules at the plasma
      membrane of mdx mouse skeletal muscles: a fracture-label electron microscopic
      study.
AB  - To analyze the molecular mechanism of the increased caveolin 3 activities in
      dystrophin-deficient muscles, we investigated three-dimensionally the changes in
      caveolin 3 molecular distribution and density at the sarcolemma of mdx mice by
      the fracture-label electron microscopic technique. At the sarcolemma of skeletal
      muscles from mdx mice, the densities of gold particles associated with caveolae,
      non-associated with caveolae and arranged circularly without caveolae were higher
      than those in control mice (P<0.01, P<0.01 and P<0.05 by two-tailed t-test),
      although in mdx mice, the overall arrangement of gold particles appeared to be
      irregular. These findings may reflect the active process of caveolar formation
      and the results of the disrupted protein-protein interaction in dystrophin
      deficient muscle plasma membrane.

PMID- 12044649
TI  - The administration of complement component C9 augments post-ischemic cerebral
      infarction volume in neonatal rats.
AB  - To determine whether ischemic cerebral infarction is mediated in part by
      complement component C9, C9-deficient neonatal rats were subjected to unilateral
      cerebral ischemia. Brains were harvested 24 h later, stained with 2,3,5-triphenyl
      tetrazolium chloride, and cerebral infarct volumes were quantified by computer
      based planimetry. Compared with buffer, prophylactic intraperitoneal (i.p.)
      administration of the complement inhibitors soluble complement receptor type 1
      (sCR1), a molecular hybrid of sCR1 and the selectin inhibitor sialyl Lewis x
      (sCR1-sLex), or cobra venom factor did not affect the cerebral infarct volume. In
      contrast, i.p. human C9 (75 microg/g body weight) significantly increased the
      volume of infarct located 6 through 10 mm posterior to the frontal pole.
      Therefore, in the post-ischemic brain, C9 was neurotoxic and augmented the focal
      cerebral infarct volume.

PMID- 12044651
TI  - Amygdalofugal modulation of the vago-vagal gastric motor reflex in rat.
AB  - In experiments on urethane anaesthetized rats the influence of electrical
      stimulation of the central nucleus of the amygdala (CNA) on gastric motility and
      activity of gastric-related neurons of the dorsal vagal complex was studied.
      Stimulation of the CNA effected spontaneous gastric motility and caused both
      excitatory and inhibitory changes of vagal-induced gastric relaxation. The most
      significant effects, mainly inhibitory, were observed under stimulation of the
      medial CNA. This amygdaloid area was found to influence activity of gastric
      related neurons of the dorsal vagal complex. Excitatory and inhibitory changes of
      their vagal-induced responses under the amygdala stimulation manifested as
      general modulation of all phases of the reaction or selective modulation of some
      of them. These mechanisms may lie at the base of amygdalofugal modulation of
      gastric reflex activity.

PMID- 12044650
TI  - Inhibition of nitric oxide synthase influences the activity of striatal neurons
      in the rat.
AB  - The activity of single units in the striatum of urethane-anesthetized rats was
      recorded before and after the systemic administration of 7-nitro-indazole (7-NI;
      50 mg/kg intraperitoneally), a selective inhibitor of neuronal nitric oxide (NO)
      synthase. Two neuronal types were clearly distinguishable electrophysiologically,
      on the basis of either discharge frequency pattern or features of the individual
      spike waveform (spike duration, negative phase/total duration ratio, and negative
      phase/total amplitude ratio). Only sporadically discharging neurons (basal firing
      rate, <0.1 spikes/s) were influenced by 7-NI, which caused a statistically
      significant increase in their firing rate. In contrast, the activity of
      continuously discharging neurons (basal firing rate, 4-6 spikes/s) was not
      affected. We hypothesize that NO neurotransmission could exert a tonic inhibitory
      influence upon sporadically discharging striatal neurons, which are presumably
      striatal output neurons.

PMID- 12044652
TI  - Mismatch negativity shows that 3-6-year-old children can learn to discriminate
      non-native speech sounds within two months.
AB  - Using 3-6-year-old children as subjects, we describe the neural plasticity
      accompanying the concurrent learning of a foreign language in a natural
      environment. Children were monitored for 6 months as they either enrolled in
      schools or daycare centers where only Finnish was spoken (Control group) or as
      they joined a French school or a daycare center where French was spoken 50-90% of
      the time (Experimental group). Whereas mismatch negativity (MMN)--a brain's
      electrical change-detection response--for a French speech contrast was initially
      absent or very small in both groups, it was conspicuous 2 months after Finnish
      children had joined a French kindergarten. Consequently, the data suggest that
      youngsters can learn to distinguish non-native speech sounds in natural language
      environment without any special training in just a couple of months. Accordingly,
      these data herald the vast potential MMN may entail for studying language
      learning, especially in situations where behavioral responses cannot be readily
      elicited.

PMID- 12044653
TI  - Methamphetamine-induced increase in striatal p53 DNA-binding activity is
      attenuated in Cu,Zn-superoxide dismutase transgenic mice.
AB  - The striatal DNA-binding activities of p53 as a transcription factor were
      gradually increased at several days after a single methamphetamine (METH)
      injection, while they were more rapidly increased within several hours after
      repeated METH injections (x4 with a 2 h interval). The elevation of striatal p53
      DNA-binding after repeated METH injections was markedly attenuated in Cu,Zn
      superoxide dismutase transgenic mice, but not affected by treatments with N
      methyl-D-aspartate or D1 receptor antagonists. The present results suggest that
      METH-induced production of reactive oxygen species activates striatal p53 DNA
      binding activity; this, in turn, may activate other downstream pathways that are
      responsible for chronic neurotoxicity of METH.

PMID- 12044654
TI  - Endothelin induced cerebral vasoconstriction in rainbow trout, detected in a
      novel in vitro preparation.
AB  - We have here developed an in vitro method for examining cerebral
      vasoconstriction/vasodilation in fish brain tissue, relying on microscopic
      observation of the diameter of an artery (denoted tectal artery) on the ventral
      side of the isolated optic tectum of rainbow trout (Oncorhynchus mykiss). Using
      this technique, we show that endothelin-1 (ET-1) is a powerful vasoconstrictor in
      rainbow trout brain. When surperfused over the optic tectum, 1.0-2.5 nM of ET-1
      caused 23 and 46% reductions, respectively, in the tectal artery diameter. This
      vasoconstriction could be completely blocked by the endothelin receptor
      antagonist bosentan. ET-1 is the first substance shown to constrict cerebral
      arteries in fish.

PMID- 12044655
TI  - Changes in molecular isoform distribution of acetylcholinesterase in rat cortex
      and cerebrospinal fluid after intracerebroventricular administration of amyloid
      beta-peptide.
AB  - Previous studies have shown that an abnormal salt-soluble form of G(1)
      acetylcholinesterase (AChE) is increased in the Alzheimer's disease (AD) brain.
      The aim of the present study was to examine changes in AChE activity in an in
      vivo model of beta-amyloid peptide (A beta) administration. Rats received
      intracerebroventricular injections of A beta(25-35) (20 microg/day for seven
      days). Levels of AChE were measured in cerebral cortex and cerebrospinal fluid
      (CSF) after two months. A beta(25-35) administration did not alter total AChE
      activity in the cerebral cortex or CSF. However, analysis of salt-extractable
      AChE isoforms revealed an increase in the proportion of G(1) in both cortex and
      CSF, similar to that previously observed in AD patients. The results support the
      view that changes in AChE isoform pattern in the AD brain are a direct
      consequence of A beta accumulation.

PMID- 12044656
TI  - Human anterior cingulate cortex is activated by negative feedback: evidence from
      event-related potentials in a guessing task.
AB  - It has been controversially discussed whether the error-related negativity (ERN)
      or error negativity (N(e)), an electrophysiological index of anterior cingulate
      activation, reflects response conflict or response evaluation subserving error
      monitoring processes. We investigated event-related potentials (ERPs) in a
      guessing task which did not induce response conflict. Subjects had to guess which
      of the four aces of a French card play would be presented next and received
      feedback at random. We observed a negative ERP deflection in trials following
      negative feedback which was identified as ERN/N(e). Dipole analysis of scalp
      potentials indicated sources in the anterior cingulate and left inferior
      prefrontal cortex. The observation of the ERN/N(e) following negative feedback
      during guessing suggests that this ERP component mirrors response evaluation
      processes comparing expected and actual response outcome rather than response
      conflict.

PMID- 12044657
TI  - Insulin-like growth factor I partly prevents axon elimination in the neonate rat
      optic nerve.
AB  - Developmental neuronal death ensues after access of innervating neurons to target
      derived neurotrophic factors is restricted. Recent evidence suggests, however,
      that growth factors such as those of the insulin family modulate neuronal death
      through autocrine/paracrine mechanisms. In rats, retinal ganglion neurons (RGNs)
      undergo massive death during early postnatal life. During this same period, the
      expression of various members of the insulin-like growth factor I (IGF-I) protein
      family is down regulated. To evaluate whether ocular IGF-I might modulate RGN
      death, we administered IGF-I in the posterior chamber of the eye of newborn rats.
      Optic nerve fiber number was estimated in control and IGF-I treated animals at
      postnatal day 5 when RGN death peaks. Intraocular IGF-I treatment at birth partly
      prevented optic nerve fiber elimination. Because the axon number in the optic
      nerve correlates to some extent with the RGN number, these results suggest that
      IGF-I may modulate RGN death in vivo through local interactions.

PMID- 12044658
TI  - Saccadic dysmetria following inactivation of the primate fastigial oculomotor
      region.
AB  - The caudal part of the fastigial nucleus, or the fastigial oculomotor region
      (FOR), plays an important role in executing accurate saccades. Inactivation of a
      monkey FOR leads to dysmetric saccades. Currently available data suggest that the
      dysmetria could be described as a parametric, uniform change in saccadic gain or,
      alternatively, as a constant error in the specification of the saccadic goal. To
      discriminate between these two possibilities, we examined the effect of FOR
      inactivation in the monkey. After a unilateral injection of muscimol into the
      FOR, ipsiversive saccades overshot a target. Gains were similar for movements of
      different sizes. The overshoot increased proportionately with the target distance
      and had a very small constant component. The present study indicates that the
      hypermetria of ipsiversive saccades after inactivation of the monkey FOR is
      primarily due to a uniform gain increase for all sizes of saccades.

PMID- 12044659
TI  - Effect of acute caffeine on severity of harmaline induced tremor in rats.
AB  - Recent studies suggest an association between caffeine consumption and tremor.
      However, the available literature is scanty and inconclusive. The present study
      was undertaken to investigate the effect of acute caffeine treatment on harmaline
      induced tremors in the rat. Four groups of male Sprague-Dawley rats (six animals
      in each group) weighing 88+/-2 g were administered harmaline (10 mg/kg,
      intraperitoneally (i.p.)) for inducing experimental tremors. The rats in group 1
      served as controls and received normal saline, whereas the animals in groups 2, 3
      and 4 were given caffeine (i.p.) at doses of 50, 100 and 150 mg/kg, respectively
      60 min after harmaline administration. The latency of onset, intensity and
      duration of tremor and electromyographic (EMG) responses were recorded. Treatment
      of rats with caffeine resulted in a significant increase in the intensity and
      duration of harmaline induced tremors. Caffeine also enhanced the EMG amplitude
      in harmaline treated animals. In conclusion, the results of this study suggest
      that acute treatment with caffeine significantly potentiates the severity of
      harmaline induced tremors in rats.

PMID- 12044660
TI  - Pulse-mode scanning ion conductance microscopy--a method to investigate cultured
      hippocampal cells.
AB  - Scanning ion conductance microscopy (SICM) takes advantage of the increase in the
      resistance which occurs if a glass microelectrode is closely approached to a
      poorly conducting membrane (Science 243 (1989) 641) and has been shown to be a
      promising technique to study membranes of living cells (Biophys J 73 (1997a) 653;
      J Microsc 188 (1997b) 17). Based on a newly designed set-up on top of an inverted
      light microscope in combination with a speed optimized low noise intracellular
      amplifier, a novel mode for control of the distance between the probe and surface
      has been developed. By application of current pulses, the change in the
      resistance is monitored independently from electrode drift and parasitic DC
      currents. We demonstrate the applicability by showing first high-resolution
      images of neural cells produced with the pulse-mode operated SICM.

PMID- 12044661
TI  - Rapid and reproducible methods using fluorogold for labelling a subpopulation of
      cervical motoneurons: application in the wobbler mouse.
AB  - A murine model of motoneuron disease, the wobbler mouse, is characterized by a
      selective loss of cervical spinal cord motoneurons. To determine the number of
      motoneurons that degenerate in mice with ongoing disease, we have developed two
      rapid and reproducible methods for labelling specific pools of cervical
      motoneurons using the retrograde tracer fluorogold. The motoneurons can be
      labelled either by capsule application of the tracer onto the sectioned musculo
      cutaneous, median and ulnar nerves or by intramuscular (i.m.) injection of the
      tracer into the biceps brachii muscle and flexor muscles of the forelimb. In wild
      type animals, the largest number of retrogradely labelled motoneurons was found 4
      days following capsule application ( approximately equal 1900 motoneurons
      labelled) and 6 days after i.m. injection ( approximately equal1500 motoneurons
      labelled). Application of these techniques in 5 week-old wobbler mice showed a
      36% loss of motoneurons 4 days following tracer application to the cut nerves and
      a 16% loss 6 days after i.m. injections as compared to values obtained in age
      matched wild-type animals in the same conditions. Our results indicate that these
      procedures can be applied to any rodent model to analyse quantitatively the loss
      of specific subpopulations of cervical motoneurons and are valuable tools for
      evaluating novel therapeutics.

PMID- 12044663
TI  - The assessment of nociceptive and non-nociceptive skin sensitivity in the
      Japanese quail (Coturnix japonica).
AB  - We evaluated the efficacy of two nociceptive tests, the hot water (HWT) and the
      foot pressure tests (FPT), and one non-nociceptive test (Semmes-Weinstein test,
      SWT) in assessing skin sensitivity in conscious Japanese quail. All stimuli
      elicited a reflex-like, strongly reproducible response. Responses in the HWT and
      FPT were identified as typical nocifensive flight-fight behavior. In untreated
      birds, these responses occurred at temperatures and forces described previously
      as noxious. In the SWT, two responses were observed: a slight ruffling of the
      cloacal gland feathers due to the stimulation of the cloacal gland, and a brief
      extension of the limbs due to the stimulation of the ilium or pectoral apterium.
      These reactions occurred at intensities recognized as innocuous. Morphine
      significantly altered the response latency and threshold in the HWT and FPT, but
      had no effect in the SWT. However, the SWT response threshold was significantly
      increased by local application of xylocaine. Taken together, the pattern of the
      responses, the intensities and the effects of morphine and xylocaine allowed to
      distinguish between nociceptive and non-nociceptive tests. They also demonstrate
      the efficacy of these tests to evaluate skin sensitivity in quail and to assess
      its modulation by chemical factors that affect somatosensory processes.

PMID- 12044664
TI  - EZ-tracing: a new ready-to-use algorithm for magnetic resonance tractography.
AB  - A new algorithm for tractography based on diffusion tensor analysis (DTA) is
      presented. This method, called EZ-tracing, is based on a new algorithm for
      analyzing DTA data, lambda chart analysis (LCA), and effectively overcomes the
      main shortcomings of previous methods for tractography. EZ-tracing is written in
      MATLAB scripting language (MathWorks, Natick, MA, USA) and can be implemented on
      any of the common operating systems, such as Microsoft Windows, UNIX, and LINUX.
      The program is available in public at coe@bri.niigata-u.ac.jp.

PMID- 12044662
TI  - A gelatin in situ-overlay technique localizes brain matrix metalloproteinase
      activity in experimental focal cerebral ischemia.
AB  - To determine the activity of matrix metalloproteinases (MMP), especially MMP-2
      and MMP-9, which play an important role in ischemic stroke and intracerebral
      hemorrhage, we adapted a simple and rapid method for localizing gelatinase
      activity to a gelatin film in situ-overlay technique previously used in cancer
      research. Ten micrometer cryosections of rat brain from controls and animals
      subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient
      cerebral ischemia) were used. After thawing, a gelatin film with a polyester base
      was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S,
      and then discolored in bi-distilled water. Non-staining areas on the film
      corresponded to lysis zones, caused by activated MMPs. This was proven by MMP
      incubation at various concentrations on the plain gelatin film and pretreatment
      with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic
      brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP
      activity, and also MMP-2 immunohistochemistry to detect the possibly cellular
      origin of MMPs. Normal rat brain exhibited a low background activity, which was
      visible as a light halo-like lysis zone over and around the brain. Areas in
      normal brain with medium MMP activity were within the white matter (corpus
      callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high
      activity lysis zones within the infarcted area (detected by microtubuli
      associated protein-2 staining). These zones consisted of microscopically small
      lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed
      that especially microvessels expressed MMP antigen. SDS-PAGE zymography
      differentiated between a high level of activated MMPs in the ischemic area and a
      low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay
      technique is able to localize MMP activity in ischemic rat brain tissue on a
      microscopic level.

PMID- 12044666
TI  - Choosing a wavelet for single-trial EMG.
AB  - A wavelet analysis was developed to measure the timing of multiunit bursts in
      surface electromyograms (EMGs) from single trials. EMG data were taken from
      eleven elbow and/or shoulder muscles during reaching movements in six different
      directions, at a range of speeds. A relatively simple wavelet (db2) was chosen,
      and the analysis focused on wavelet coefficients at an intermediate scale (D3),
      where the wavelet length approximately matched the wavelengths present in EMG
      bursts. Burst times were identified from the peaks of the coefficient traces and
      were plotted as a function of movement time. Linear regression revealed
      significant relations in most cases, and thus served to validate the wavelet
      burst identification. With a few exceptions, burst timing scaled in a manner
      approximately similar to the scaling of movement time. As shown previously with
      different analytical methods, both within and across joints, EMG bursts were not
      confined to distinct 'agonist' and 'antagonist' time frames, but instead showed a
      variety of phases relative to speed or joint torque.

PMID- 12044665
TI  - High-resolution phosphor imaging: validation for use with human brain tissue
      sections to determine the affinity and density of radioligand binding.
AB  - This study investigated the suitability of high-resolution storage phosphor
      imaging for the quantitative analysis of radioligand binding to human brain
      tissue. Hence, the binding of [(3)H]mazindol to the dopamine transporter in
      caudate-putamen tissue homogenates or frozen tissue sections apposed to either
      autoradiographic film or phosphor imaging plates was measured. Estimates of
      binding affinity were similar for homogenate studies and phosphor imaging plates
      (Kd=6.44+/-0.14 and 6.91+/-0.47 nM, respectively), but higher values were
      obtained with film autoradiography (Kd=11.31+/-0.82 nM). The density of binding
      was similar for both autoradiographic techniques (Bmax=371.9+/-30.8 fmol/mg
      estimated tissue equivalent, ETE (imaging plate) and 425+/-13.77 fmol/mg ETE
      (film)), although lower values were obtained from tissue homogenates
      (Bmax=64.27+/-6.74 fmol/mg wet weight). These results suggest that high
      resolution phosphor imaging can be used to analyse radioligand binding parameters
      in human brain tissue. Moreover, the reduced exposure time of phosphor imaging
      plates (e.g. 7 days vs 5 weeks) allows results to be obtained more rapidly than
      with conventional film autoradiography.

PMID- 12044667
TI  - Classification of neural signals by a generalized correlation classifier based on
      radial basis functions.
AB  - A common problem in neuroscience is to identify the features by which a set of
      measurements can be segregated into different classes, for example into different
      responses to sensory stimuli. A main difficulty is that the derived distributions
      are often high-dimensional and complex. Many multivariate analysis techniques,
      therefore, aim to find a simpler low-dimensional representation. Most of them
      either involve huge efforts in implementation and data handling or ignore
      important structures and relationships within the original data. We developed a
      dimension reduction method by means of radial basis functions (RBF), where only a
      system of linear equations has to be solved. We show that this approach can be
      regarded as an extension of a linear correlation-based classifier. The validity
      and reliability of this technique is demonstrated on artificial data sets. Its
      practical relevance is further confirmed by discriminating recordings from monkey
      visual cortex evoked by different stimuli.

PMID- 12044668
TI  - Tracking sodium channels in live cells: confocal imaging using fluorescently
      labeled toxins.
AB  - One particularly important class of ion channels in excitable cells are the
      voltage-dependent sodium channels (VDSC). Knowledge of the distribution of VDSC
      in living cells is important for studies of neuronal excitability, development,
      and plasticity. Here, we demonstrate a new method for visualizing the spatial
      distribution of VDSC in living cells. To illustrate the capabilities of the
      technique, the distribution of VDSC in GH3 cells was revealed with fluorescent
      derivatives of the alpha-type and beta-type scorpion toxins in conjunction with
      laser scanning confocal microscopy. Cells exhibited fluorescent hot spots on the
      surface of the membrane. This characteristic staining pattern was prevented by
      pre-incubation with unlabeled native toxins and blocked by membrane
      depolarization for alpha-type toxins. Labeling was not observed in cells lacking
      sodium channels (HEK 293) after incubation with fluorescent-labeled toxins. Image
      processing techniques were applied to identify the location of each cluster of
      labeled VDSC in these cells. The proposed method eliminates artefacts commonly
      introduced during sample preparation for immunostaining and should prove to be a
      valuable research tool for investigating VDSC distribution in living specimens.

PMID- 12044669
TI  - Gait analysis as an objective measure in a chronic pain model.
AB  - The aim of this study was to investigate objective characterisation of gait as a
      marker of the chronic pain of adjuvant arthritis (AA). Video recorded images of
      spontaneous rat ambulations were analysed to quantify various temporal and
      spatial parameters and compare these between the AA and control groups. Changes
      were also recorded after the administration of a single dose of buprenorphine (15
      ?g). Individual temporal parameters were significantly reduced (velocity
      (P=0.05), stride length (P=0.007), single stance time (P<0.001), swing time
      (P=0.001)), or increased (dual stance time (P<0.001)) at 10 days in the AA group
      compared to control. The rear paws showed reduced ground contact and the fore
      paws an increase in proximal pad and decrease in digit area, although these
      changes were not all statistically significant. Some of the gait parameters
      showed significant reversal following administration of buprenorphine (velocity
      (P<0.001) and stride length (P<0.001) were increased and single stance time
      (P=0.014) reduced). It is proposed that changes in gait are a marker of AA
      chronic pain in this model. These behavioural changes were significant at a very
      early stage (day 10), before the development of physical deformities and increase
      in paw volume and might permit an earlier detection of pain than other models.

PMID- 12044670
TI  - The neuA/flmD gene cluster of Helicobacter pylori is involved in flagellar
      biosynthesis and flagellin glycosylation.
AB  - Helicobacter pylori possesses a gene (HP0326/JHP309) homologous to neuA of other
      bacteria, encoding a cytidyl monophosphate-N-acetylneuraminic acid synthetase
      homologous enzyme in its N-terminal portion. We analysed the function of this
      gene, which is controlled by a flagellar class 2 sigma(54) promoter, in flagellar
      biosynthesis. HP0326/JHP309 actually represents a bicistronic operon consisting
      of a neuA and a flmD-like putative glycosyl transferase gene. An isogenic flmD
      mutant synthesized basal bodies but no filaments, was non-motile, and expressed
      severely reduced amounts of a FlaA flagellin of reduced molecular mass. FlaA
      flagellin was found to be glycosylated in its exported form within the flagellar
      filament, but not inside the cytoplasm. Glycosylated FlaA was not detectable in
      the flmD mutant. Together with other genes in the H. pylori genome, a proposed
      function of the neuA/flmD gene products could be to provide a pathway for
      glycosylation of flagellin and other extracytoplasmic molecules during type III
      secretion.

PMID- 12044671
TI  - Identification of Brachyspira hyodysenteriae-specific DNA fragments using
      representational difference analysis.
AB  - Two novel Brachyspira hyodysenteriae-specific DNA fragments, designated as Bh100
      and Bh400, were identified using representational difference analysis. To isolate
      the fragments the combined DNA of the Brachyspira pilosicoli, Brachyspira
      intermedia, Brachyspira murdochii and Brachyspira innocens reference strains was
      subtracted from the genome of B. hyodysenteriae strain B204. Both fragments were
      present in a single copy and mapped to different positions on the genome of B.
      hyodysenteriae B78(T). Larger fragments encompassing the continuous open reading
      frames (ORF) of Bh100 and Bh400 were cloned and analysed. Whereas the ORF of 2130
      bp encompassing Bh100 did not show homology to any known bacterial protein, Bh400
      was part of a putative operon with significant homology to the phosphotransferase
      system of Bacillus subtilis.

PMID- 12044672
TI  - A liquid-based method for the assessment of bacterial pathogenicity using the
      nematode Caenorhabditis elegans.
AB  - Caenorhabditis elegans has previously been used as an alternative to mammalian
      models of infection with bacterial pathogens. We have developed a liquid-based
      assay to measure the effect of bacteria on the feeding ability of C. elegans.
      Using this assay we have shown that Pseudomonas aeruginosa strain PA14,
      Burkholderia pseudomallei and Yersinia pestis were able to inhibit feeding of C.
      elegans strain N2. An increase in sensitivity of the assay was achieved by using
      C. elegans mutant phm-2, in place of the wild-type strain. Using this assay,P.
      aeruginosa PA01 inhibited the feeding of C. elegans mutant phm-2. Such liquid
      based feeding assays are ideally suited to the high-throughput screening of
      mutants of bacterial pathogens.

PMID- 12044673
TI  - Mutagenesis of key amino acids alters activity of a Saccharomyces cerevisiae endo
      polygalacturonase expressed in Pichia pastoris.
AB  - A polygalacturonase (PG)-encoding gene from Saccharomyces cerevisiae (PGU1) was
      successfully expressed in the methylotrophic yeast Pichia pastoris. PG secretion
      was efficiently directed by the S. cerevisiae alpha-factor signal sequence, while
      the native (PGU1) leader peptide was unable to direct protein export in P.
      pastoris. The level of PGU1 activity achieved in P. pastoris was significantly
      enhanced when compared to activity using the same gene in S. cerevisiae.
      Expression of PG proteins, engineered by site-directed mutagenesis, in P.
      pastoris showed that aspartic acid residues at positions 179, 200, and 201, and
      histidine 222 were essential for enzyme activity. Mutation of the two potential
      glycosylation sites in PGU1 showed that the two residues individually (N318D,
      N330D) did not affect secreted enzyme activity, but the double mutant caused a
      50% reduction in enzyme activity when compared to the wild-type PGU1
      transformant.

PMID- 12044676
TI  - Decarboxylase activity involved in methyl ketone production by Staphylococcus
      carnosus 833, a strain used in sausage fermentation.
AB  - Staphylococcus carnosus strain 833, inoculated into sausage, increased the levels
      of methyl ketones which contributed to the cured aroma. These ketones were
      predicted to arise from incomplete beta-oxidation followed by a decarboxylation.
      To check this hypothesis, we measured the beta-decarboxylase activity in resting
      cells of S. carnosus grown in complex or in synthetic medium, using as substrate
      a beta-ketoacid, which can be an intermediate of the beta-oxidation pathway. This
      activity was present throughout the growth period. The enzyme appeared to be
      constitutive because no induction was observed. High aeration, a pH of 5 and the
      presence of nitrate promoted the production of methyl ketones.

PMID- 12044674
TI  - Identification and characterization of the Bacillus subtilis D
      glucarate/galactarate utilization operon ycbCDEFGHJ.
AB  - In the course of the Bacillus subtilis functional genomics project, an open
      reading frame called ycbG whose product is classified as a transcriptional
      regulatory protein with a helix-turn-helix motif in the putative D
      glucarate/galactarate utilization operon (ycbCDEFGHJ) was initially screened as
      the gene disruptant that exhibits a defect that blocked the early stage of
      sporulation. However, the transcription of ycbCDEFG was extremely highly induced
      in response to nutrient exhaustion by the disruption of ycbG, but inactivation of
      the transcription from upstream ycbC in the ycbG mutant restored the sporulation
      efficiency, suggesting that the inappropriate over-production of the ycbCDEFG
      gene products inhibits efficient sporulation. We further analyzed the role of the
      ycbCDEFGHJ cluster and found that (i) a unit of ycbCDEFGHJ was induced by either
      D-glucarate or D-galactarate, and (ii) the cell growth was inhibited by the
      mutation of the ycbF and ycbH genes, that respectively encode the putative
      proteins, D-glucarate dehydratase and D-galactarate dehydratase on plates
      supplemented with D-glucarate and D-galactarate, respectively, as the sole carbon
      source. Our results indicate that the ycbCDEFGHJ genes are involved in the
      utilization of D-glucarate and D-galactarate in B. subtilis.

PMID- 12044675
TI  - Pasteurella multocida exbB, exbD and tonB genes are physically linked but
      independently transcribed.
AB  - The exbB, exbD and tonB genes of the Pasteurella multocida animal pathogen have
      been cloned by complementation of an Escherichia coli tonB mutant. Despite these
      three genes being physically linked, RT-PCR analysis, lacZ transcriptional
      fusions and construction of insertional mutants have demonstrated that they do
      not constitute an operon, but rather are transcribed independently from each
      other. Furthermore, expression of these three genes is under iron control as
      revealed by lacZ fusions and Fur titration assay analysis. Moreover, each of
      these three genes is necessary for the virulence of P. multocida cells and all of
      them contribute equally to the infectious process of this microorganism.

PMID- 12044678
TI  - Succinate synthesis and excretion by Penicillium simplicissimum under aerobic and
      anaerobic conditions.
AB  - Succinate is an interesting chemical for industries producing food and
      pharmaceutical products, surfactants, detergents and biodegradable plastics.
      Succinate is produced mainly by a mixed-acid fermentation process using
      anaerobically growing bacteria. However, succinate excretion is also widespread
      among fungi. In this article we report results on the intracellular concentration
      and the excretion of succinate by Penicillium simplicissimum under aerobic and
      anaerobic conditions. The intracellular concentration of succinate increased
      slightly with the specific growth rate and strongly if the respiratory chain was
      inhibited by sodium azide or anaerobic conditions (N(2)). A strong increase of
      succinate excretion was observed if the respiratory chain was inhibited. It is
      suggested that succinate synthesis under functional (sodium azide) or
      environmental (N(2)) anaerobic conditions occurs via the reductive part of the
      tricarboxylic acid cycle. Succinate is then excreted because the oxidative part
      of the tricarboxylic acid cycle is inactive. A possible role of succinate
      synthesis in the regeneration of NAD ('fumarate respiration') is discussed.

PMID- 12044677
TI  - The effects of volatile microbial secondary metabolites on protein synthesis in
      Serpula lacrymans.
AB  - The effects of volatile secondary metabolites produced by Trichoderma
      pseudokoningii, Trichoderma viride and Trichoderma aureoviride on growth rate and
      protein synthesis in two Serpula lacrymans isolates were investigated. Mycelial
      growth was affected to differing degrees, depending on the specific interactive
      microbial couplet involved. Protein synthesis by both S. lacrymans (Forfar) and
      S. lacrymans (H28) was affected by the volatile secondary metabolites of T.
      aureoviride and T. viride, but not by those of T. pseudokoningii. Mycelial growth
      and the original pattern of protein synthesis resumed when the antagonists were
      removed. It is probable that volatile secondary metabolites have played an
      important role during the evolution of microorganisms in the context of
      community, population and functional dynamics.

PMID- 12044680
TI  - Environmental adaptation factors of two yeasts isolated from the leachate of a
      uranium mineral heap.
AB  - Two yeasts from the effluent of a uranium mineral heap were identified as Candida
      sorbophila and Rhodotorula mucilaginosa. They are well adapted to such an
      environment as shown by their tolerance to metals and acid pH. However, different
      mechanisms could be involved in the adaptation: C. sorbophila could be considered
      to be more acid-tolerant as a function of its specific growth rate and
      respiratory behavior at acidic pH in an organic medium. However, R. mucilaginosa
      was capable of growing by 1 log unit when inoculated in a sterilized leaching
      effluent or in a ferrous mineral medium, without added organic compounds. Indeed,
      the ability of R. mucilaginosa to grow in a low-nutrient environment could be as
      important a factor as its acid tolerance for coping in the isolation habitat. In
      mixed cultures with sulfide-oxidizing bacteria, no effect was observed on the
      ferrous oxidation normally carried out by these bacteria. However, a negative
      effect on both yeasts, especially in C. sorbophila, was observed, when the
      bacteria were present.

PMID- 12044679
TI  - Degradation of pyrene by indigenous fungi from a former gasworks site.
AB  - Indigenous fungi isolated from soil of a former gasworks site were investigated
      in submerged cultures with pyrene as the sole carbon source. Five fungal strains
      capable of degrading pyrene included one strain of Trichoderma harzianum and four
      strains with characteristics of the genus Penicillium. These are identified as
      Penicillium simplicissimum, Penicillium janthinellum, Penicillium funiculosum and
      Penicillium terrestre. A maximum of 75% of 50 mg l(-1) and 67% of 100 mg l(-1) of
      pyrene was removed by the fast degrading strain P. terrestre at 22 degrees C
      during 28 days of incubation. The slower degrader P. janthinellum was able to
      remove 57% of 50 mg l(-1) and about 31.5% of 100 mg l(-1) pyrene. Degradation of
      pyrene is directly correlated with biomass development. To the best of our
      knowledge, this is the first time that fungi have been reported to use pyrene as
      the sole carbon and energy source. They may be ideal candidates for effective
      bioremediation of polycyclic aromatic hydrocarbons.

PMID- 12044681
TI  - Purification and characterization of an erythromycin esterase from an
      erythromycin-resistant Pseudomonas sp.
AB  - An erythromycin esterase (molecular mass 51200 Da) was purified from Pseudomonas
      sp. GD100, which was isolated from a salmon hatchery sediment sample from
      Washington State. The pI of the protein was 4.5-4.8. The enzyme was inhibited by
      1 mM mercuric acid, and had the substrate specificity for structurally related 14
      membered macrolides, which decreased in the order of oleandomycin, erythromycin A
      and erythromycin A enol ether. The activity for erythromycin A varied with
      temperature, but the effect of pH was minimal at pH 6.0-9.0. The half-life of the
      enzyme was estimated to be 8.9 h at 35 degrees C and 0.23 h at 55 degrees C, and
      the activation energy of the catalytic reaction of erythromycin A was estimated
      at 16.2 kJ mol(-1).

PMID- 12044682
TI  - Optimization of a rapid and sensitive identification system for Salmonella
      enteritidis by capillary electrophoresis with laser-induced fluorescence.
AB  - A system coupling capillary electrophoresis (CE) with a laser-induced
      fluorescence (LIF) system for the identification of Salmonella enteritidis was
      developed. Addition of an appropriate amount of sodium alginate and NaCl to the
      running buffer made it possible to obtain a reproducible sharp peak. Two
      fluorescent staining methods using a cell-permeable nucleic acid stain and a
      salmonellae-specific polyclonal antibody were adapted to the system. The CE-LIF
      successfully detected as few as three cells per injection from a pure culture of
      S. enteritidis. The CE-LIF system can be conveniently used for rapid and highly
      sensitive identification of S. enteritidis.

PMID- 12044683
TI  - Representational difference analysis uncovers a novel IS10-like insertion element
      unique to pathogenic strains of Yersinia enterocolitica.
AB  - The method of suppressive subtractive hybridization was employed to map out
      genomic differences between the highly pathogenic Yersinia enterocolitica (Ye)
      biogroup 1B, serotype O:8 strain (WA-314) and the closely related apathogenic Y.
      enterocolitica biogroup 1A, serotype O:5 strain (NF-O). A novel IS10-like
      element, IS1330, uncovered by this technique was found to be uniquely present in
      high copy numbers among the highly pathogenic Y. enterocolitica 1B strains, while
      a single copy of the element was found in the low pathogenic Ye biogroup 4
      serotype O:3 strain. The 1321-bp repetitive element has 19-bp imperfect inverted
      terminal repeats and is bracketed by a 10-bp duplication of the target sequence.
      The predicted transposase shares high homology with the IS10 open reading frame
      of the large virulence plasmid pWR501, of Shigella flexneri, with IS10
      transposase of Salmonella typhi, and with IS1999 (tnpA) of Pseudomonas
      aeruginosa. The IS1330 tnp gene is transcribed in vitro and in vivo in HeLa
      cells. At least one copy of IS1330 flanks the recently described chromosomal type
      III secretion cluster in Y. enterocolitica WA-314, O:8, and future studies should
      shed light on whether this novel transposase mediates transposition events in
      highly pathogenic Y. enterocolitica strains, thus enhancing the genetic
      plasticity of this species.

PMID- 12044684
TI  - Rapid selection of anti-hapten antibodies isolated from synthetic and semi
      synthetic antibody phage display libraries expressed in Escherichia coli.
AB  - Antibody phage display libraries (Griffin and Tomlinson I) displaying antibody
      genes and maintained and amplified in Escherichia coli were used to isolate
      antibodies to the hapten target microcystin LR (1000 Da) conjugated to either
      bovine serum albumin or keyhole limpet haemocyanin. In competition enzyme-linked
      immunosorbent assay, bacterially expressed antibodies selected via the Griffin
      library showed at least 300 times greater sensitivity than those isolated from
      the Tomlinson library, for free microcystin. Bacterially expressed phage antibody
      libraries provide a rapid and relatively easy route for the selection of
      monoclonal antibodies specific for even the most difficult of antigenic targets
      such as free haptens.

PMID- 12044685
TI  - General expression vectors for Staphylococcus carnosus enabled efficient
      production of the outer membrane protein A of Klebsiella pneumoniae.
AB  - General expression vectors, designed for intracellular expression or secretion of
      recombinant proteins in the non-pathogenic Staphylococcus carnosus, were
      constructed. Both vector systems encode two different affinity tags, an upstream
      albumin binding protein and a downstream hexahistidyl peptide, and are furnished
      with cleavage sites for two site-specific proteases for optional affinity tag
      removal. To evaluate the novel vectors, the gene encoding the outer membrane
      protein A (OmpA) of Klebsiella pneumoniae was introduced into the vectors.
      Efficient production was demonstrated in both systems, although, as expected for
      OmpA fusions, somewhat better intracellularly, and the fusion proteins could be
      recovered as full-length products by affinity chromatography.

PMID- 12044686
TI  - Ecology of Listeria monocytogenes in the environment of raw poultry meat and raw
      pork meat processing plants.
AB  - The zoonotic Listeria monocytogenes is mainly transmitted to humans by the food
      borne route. This bacterium was often found in the environment of food processing
      plants. Therefore the aims of this study were (i) the identification of
      environmental factors associated with L. monocytogenes contamination on working
      and non-working surfaces in poultry or pork processing plants and (ii) the
      understanding of its survival in such environments. The physicochemical risk
      profiles showed that a surface in resin or plastic, rather than uneven, with
      organic residues, with a neutral pH, a low temperature and a high hygrometry was
      associated with L. monocytogenes contamination.

PMID- 12044687
TI  - Pseudomonas aeruginosa galU is required for a complete lipopolysaccharide core
      and repairs a secondary mutation in a PA103 (serogroup O11) wbpM mutant.
AB  - Insertional inactivation of wbpM in Pseudomonas aeruginosa serogroup O11 strain
      PA103 resulted in mutants exhibiting three distinct lipopolysaccharide (LPS)
      phenotypes. One mutant, PA103 wbpM-C, had a truncated LPS core and lacked O
      antigen. These defects were not complemented by the cloned wbpM gene, suggesting
      a secondary mutation was present. When the wild-type galU gene was introduced
      into strain PA103 wbpM-C containing the cloned wbpM gene, both LPS defects were
      corrected. Construction of galU mutants in P. aeruginosa serogroups O11, O5, O6
      and O17 strains led to truncation of the LPS core, indicating the involvement of
      GalU in P. aeruginosa LPS core synthesis.

PMID- 12044688
TI  - Foraging behavioural changes induced by conspecific and heterosubspecific odours
      in two strains of wild mice.
AB  - Mice in wild populations of the two subspecies Mus musculus domesticus and Mus
      musculus musculus may potentially compete for food. Because of the importance of
      olfaction in mice, we hypothesised that the presence of unfamiliar conspecific or
      heterosubspecific chemical cues could play a role in access to and use of food
      resources. We used an experimental design that tested this assumption with males
      from two strains, originated from wild populations of these subspecies, as
      subjects. Exploratory activity, latency of food approach, time and frequency on
      the food area, number of seeds eaten and foraging rate (number of seeds
      eaten/time on the food areax100) were compared for three different categories of
      odours (own, same strain and other strain odours) in both strains. In a foraging
      context, unfamiliar odours induced behavioural changes in male mice, especially
      an increase in exploratory activity from the more (same strain) to the less
      similar odour (different strain), and a reduction of time spent in the food area.
      Odour similarity related to genetic proximity in Mus and the cost-benefit ratio
      of an encounter are two possible explanations for the different processes
      involved in the treatment of odours in these two strains of mice.

PMID- 12044689
TI  - A simple spatial alternation task for assessing memory function in zebrafish.
AB  - A series of studies was initiated to examine learning and memory function in the
      zebrafish (Danio rerio) by using a simple spatial alternation paradigm for a food
      reward. Fish were fed on alternating sides of a divided fish tank, with a red
      card displayed on one side serving as a visual means of orientation. Although
      responses were recorded at cue (light tap on the tank), 5 s after cue (as food
      was delivered), and 5 s after food delivery, the learning test was choice of a
      correct side of the tank to receive food. Therefore, an accurate level of an
      animal's achievement of the spatial task was represented by responses at food
      delivery. Data collected from 11 separate experiments indicated that zebrafish
      learned to alternate for a food reward. Further, statistical analysis showed that
      the zebrafish learned the task in the first half of the experiment as exhibited
      by a calculated t1/2 of 13.9 trials. Zebrafish could recall the task after a
      short period of 10 days with no testing. The alternating behavior was
      extinguished by withholding the food reward. Thus, the spatial alternation task
      can be learned easily by zebrafish, and may be useful in addressing learning and
      memory functions in vertebrate animals using zebrafish as a model organism.

PMID- 12044690
TI  - Information in the behavior stream.
AB  - The dynamic of a series of responses for four pigeons is analyzed using a
      discrete fast Fourier transform (FFT) and a measure of behavior's predictability.
      FFTs of moment-to-moment response rates reliably exhibited a continuous
      distribution for three of the four birds, with most of the power falling in the
      low frequencies-red noise. An information analysis of the predictability of a
      series of inter-response times (IRTs) reveals that there is some gain in
      prediction by knowing past behavior; moreover, predictability increases the more
      past behaviors are taken into account. However, the further into the future these
      predictions are extended, the less reliable they become-entropy. These findings
      suggest that the dynamic controlling behavior at the level of the individual
      response is, to some extent, deterministic and probably chaotic.

PMID- 12044691
TI  - Working memory of action: a comparative study of ability to selecting response
      based on previous action in New World monkeys (Saimiri sciureus and Callithrix
      jacchus).
AB  - Working memory of the outcome of one's own action is important for organizing and
      learning appropriate behaviors in a given condition. To examine whether non-human
      primates with different neocortical sizes show different abilities regarding
      working memory for action, the performance of squirrel monkeys (Saimiri sciureus)
      and common marmosets (Callithrix jacchus) in a kind of delayed-response task was
      compared. In this task, subjects were required to select a response based on
      short-term memory of the outcome of their own prior action, which requires
      working memory of action. These monkeys have a similar phylogenetic status (i.e.
      Ceboidea), but the size of the neocortex relative to the rest of the brain
      (relative size of the neocortex) is quite different. We found that both two
      species could attend to and remember their own actions and could select a
      response based on that memory. However, the performance level was higher for
      squirrel monkeys than for marmosets. These results suggest that non-human
      primates with differentially developed neocortices have different abilities
      regarding working memory of action.

PMID- 12044692
TI  - Unequal interval time-place learning.
AB  - In time-place learning tasks food availability depends upon both spatial and
      temporal variables. For example, food might be first available at location one,
      then location two, then location three, and finally location four. To date, the
      duration of food availability at each of the locations have been identical (e.g.
      for 4 min). The major purpose of the present experiment was to determine if rats
      can successfully learn a time-place task in which four locations provided food
      for different durations. Lever 1 intermittently produced food for 6 min, then
      Lever 2 produced food for 4 min. Lever 3 and 4 provided food for 2 and 8 min,
      respectively. Rats were able to learn this unequal interval time-place task.
      However, their behavior on this unequal interval time-place task was not in
      agreement with Scalar Expectancy Theory/Weber's Law.

PMID- 12044693
TI  - Interval timing in rats: tracking unsignaled changes in the fixed interval
      schedule requirement.
AB  - The present experiment examined interval timing in rats under dynamic conditions.
      A session began with FI60 s intervals, changed to a FI20 s, FI30 s, or FI40 s
      schedule at an unpredictable point, and then returned to a FI60 s schedule after
      the rats received 1, 8, or 24 successive short FI intervals. Variations in the
      duration and number of shorter intervals occurred across sessions and conditions.
      We observed rapid control of wait time duration by the FI duration of the
      preceding interval (one-back tracking), and changes in wait time depended on the
      number and duration of the shorter intervals. Furthermore, we observed
      proportional and scalar timing effects in overall wait time duration. The results
      provide information about the relation between interval timing under dynamic and
      steady state conditions.

PMID- 12044694
TI  - Food imprinting and subsequent prey preference in the lynx spider, Oxyopes
      salticus (Araneae: Oxyopidae).
AB  - This object of this study was to determine if early feeding experience can affect
      subsequent prey choice in lynx spiderlings (Oxyopes salticus), and if so, is it
      evidence for food/olfactory imprinting. After emergence from the egg sac, three
      groups of 10 spiderlings were each fed exclusively for a 1-week period on one of
      three naturally-occurring prey species (crickets): group 1 fed on nymphs of
      Gryllotalpa hexadactyla; group 2 (Dialeurodes citrifoli); group 3 (Microcentrum
      rhombifolium). Following this, they were tested for subsequent prey preference in
      choice tests conducted in a plastic arena. Each spiderling was presented
      simultaneously with one individual of each prey species in a randomized design.
      Spiderlings exhibited a significant first preference for the original diet. Thus,
      experience with certain foods encountered by newly hatched spiderlings can affect
      subsequent prey preference in this species. Given the primacy of the early
      experience, the results are best interpreted in terms of imprinting and represent
      the first demonstration of olfactory imprinting in a spider.

PMID- 12044696
TI  - Carcinoma of esophagus: radiologic diagnosis and staging.
AB  - Esophageal carcinoma is an uncommon malignancy accounting for approximately 7% of
      gastrointestinal tract cancers and 1% of all cancers. Esophageal cancer still
      remains one of the most lethal of all cancers. Since a multimodality approach is
      presently used to treat esophageal cancer, early radiologic diagnosis and
      accurate tumor staging are essential to direct therapy toward cure or palliation.
      This article presents a review of radiologic diagnosis and staging of esophageal
      cancer.

PMID- 12044697
TI  - Carcinoma of stomach and duodenum: radiologic diagnosis and staging.
AB  - Gastric carcinoma is one of the leading causes of cancer mortality worldwide.
      Accurate preoperative staging of gastric cancer is important in planning the most
      effective therapy toward cure or palliation. This article reviews the radiologic
      diagnosis and staging of gastric cancer.

PMID- 12044698
TI  - Radiologic evaluation and staging of small intestine neoplasms.
AB  - The small intestine is an uncommon location for neoplasms in either clinical or
      radiological practice. Because of its anatomic location and morphology, diagnosis
      of the diseases that affect small intestine pose difficulties. Symptoms are
      nonspecific and endoscopy is commonly unsatisfactory. Since early and definite
      diagnosis is crucial for prompt therapy, radiological imaging plays an essential
      role. Enteroclysis is the primary and effective radiologic modality in the
      evaluation of small bowel neoplasms. On the other hand, computed tomography
      should be the complementary radiologic method as well as for staging. In this
      review, the most common neoplasms of the small intestine and their common
      radiologic findings have been discussed.

PMID- 12044700
TI  - Postoperative imaging of gastrointestinal tract cancers.
AB  - Assessment in postoperative complications of gastrointestinal cancers via imaging
      modalities is of significant importance as diagnosing the cancer. Complications
      can be considered as an indicator for the success of surgical procedure, and has
      a vital importance for the patient. In this article the implications of CT, MR,
      ultrasonography and PET in these indications and their benefits are discussed.

PMID- 12044699
TI  - Colorectal carcinoma: radiological diagnosis and staging.
AB  - Colorectal carcinomas are the most common gastrointestinal tract tumors. 50-60%
      of the colorectal carcinomas originate in rectum and sigmoid colon. The new
      developments in imaging modalities have brought improvements in therapeutic
      aspects. The survival rates in these patients depend on the tumor penetration and
      the presence of regional lymph node or distant metastasis. The recurrence rates
      have decreased with the new operation techniques and preoperative radiotherapy,
      thus increasing the importance of accurate tumor staging. Double contrast barium
      enema studies enable the diagnosis while staging and follow-up is best done by
      topographic imaging techniques.

PMID- 12044701
TI  - Virtual endoscopy.
AB  - Virtual endoscopy is a new-generation technique which combines the features of
      endoscopic viewing and cross-sectional volumetric imaging. In the evaluation of
      gastrointestinal cancers, virtual endoscopy has been most commonly used in
      colorectal carcinomas and to a much lesser extent in gastric carcinomas. In this
      review, the current status of virtual colonoscopy was reviewed together with a
      brief discussion of virtual gastroscopy.

PMID- 12044702
TI  - Intervention in gastrointestinal tract: the treatment of esophageal,
      gastroduodenal and colorectal obstructions with metallic stents.
AB  - With the development of newer stent designs and delivery systems, metallic stents
      are currently established component of nonsurgical treatment of gastrointestinal
      obstructions. The use of metallic stents is not intended to be curative but
      palliative. This palliation may be intended for the rest of the patient's life
      with unresectable disease or as a temporary procedure prior to a definitive
      surgical procedure to allow time to improve the patient's overall medical
      condition or quick and noninvasive decompression of the intestinal obstruction.

PMID- 12044703
TI  - Two-year toxicity and oncogenicity study with acrylonitrile incorporated in the
      drinking water of rats.
AB  - Sprague-Dawley rats (80 per sex per control and 48 per sex in each treatment
      group) were given drinking water formulated to contain 0, 35, 100, or 300 ppm
      acrylonitrile (AN) for up to 2-years. An additional ten rats per sex per group
      were added for a 1-year interim necropsy. The equivalent doses of AN consumed
      were 0, 3.4, 8.5, and 21.3 mg/kg per day for males and 0, 4.4, 10.8, and 25.0 for
      females. Rats were closely monitored clinically with body weight, feed and water
      consumption measured at numerous intervals. Hematology, clinical chemistry, and
      urinalysis were evaluated six times. All rats were necropsied when moribund,
      found dead, or at scheduled termination, with extensive histopathology of all
      rats. Numerous adverse toxic and oncogenic effects were observed in both sexes of
      all AN treatment groups. Decreased water consumption, feed consumption, and
      concomitant body weight suppression occurred within days of study initiation and
      persisted throughout the study in all treatment groups. An early onset of Zymbal
      gland tumors in high dose male and female rats, and in the mammary gland of all
      treated groups of females, was detected in-life. Hematology, clinical chemistry,
      and urinalysis, repeatedly evaluated, were without significant biological
      effects, except for an increased urine specific gravity due to the rats lower
      water intake. Organ weights at study termination were not significantly affected.
      Mortality was high in all female treated groups, with no surviving male or female
      300 ppm rats during the last 2 months of the study. The most significant findings
      in this study were detected following gross and microscopic examination of an
      extensive list of tissues from all rats in the study. Nontumorous and tumorous
      lesions were found at an increased and/or decreased rate in a number of tissues
      of both sexes at all treatment levels. The primary nontumorous histopathologic
      effects of AN exposure occurred in the forestomach and the central nervous system
      of rats of both sexes and involved all treatment groups. A statistically
      significant increased incidence of tumors in one or more dose levels of either
      sex occurred in the central nervous system, Zymbal gland, forestomach, tongue,
      small instestine, and mammary gland. A no-observed-effect level (NOEL) was not
      identified in this study for toxicity or oncogenicity in either sex.

PMID- 12044704
TI  - Comparative chronic toxicity and carcinogenicity of acrylonitrile by drinking
      water and oral intubation to Spartan Sprague-Dawley rats.
AB  - Groups of 100 male and 100 female Spartan Sprague-Dawley rats were administered
      lifetime oral doses of Acrylonitrile (AN) by one of two routes of dosing, either
      at 0.1 or 10 mg/kg per day, 7 day per week by intubation or continually at 1 or
      100 ppm AN in their drinking water. The doses selected were designed to
      approximate the same daily intake of AN in each of two separate studies, whether
      by a single bolus dose (intubation) or a more continuous dosing regimen in
      drinking water. Each study had its own untreated control group of 100 rats per
      sex. In the drinking water study, the equivalent mean dosage of AN administered
      to males and females were 0, 0.09, and 0.15 mg/kg per day, respectively, at the 1
      ppm level, and 0, 8.0 and 10.7 mg/kg per day, respectively, for 100 ppm dose
      groups. In both studies, groups of ten rats per sex were sacrificed at 6, 12 and
      18 months and at study term. Ophthalmoscopic, hematological, clinical
      biochemistry, urinalysis and full histopathological exams were performed on
      control and high dose groups of rats in each study. Similar tests were done in
      lower dose groups, as required, to define dose-responses of observed effects. All
      animals were necropsied and underwent microscopic examination of target tissues,
      including brain, ear canal, stomach, spinal cord and any observable tissue
      masses. High dose male and female rats in both studies exhibited statistically
      decreased body weights. Food consumption and water intake were reduced only in
      the drinking water study. Due to increased deaths in groups of high dose rats of
      both studies receiving AN, all intubation test groups were terminated after 20
      months of treatment. Surviving males and females in the drinking water study were
      terminated after 22 and 19 months, respectively. Small, sometimes statistically
      significant, reductions in hemoglobin, hematocrit and erythrocyte count were
      observed in male and female rats in both high dose (10 mg/kg per day intubation
      and 100 ppm drinking water) groups from both studies. There were increases in
      absolute or relative organ weight ratios for liver and adrenal in the high dose
      intubation study groups, but could not be correlated with AN toxicity in the
      absence of adverse clinical biochemistry or microscopic findings. Similar organ
      weight findings were not observed in the drinking water study. Again, there were
      no changes in clinical biochemistry or microscopic findings in these tissues.
      Absolute kidney weights were increased in high dose male and female rats in the
      intubation study and high dose female rats only in the drinking water study. Male
      and female rats from high dose groups in each study had a higher incidence of
      palpable masses of the head and the nonglandular stomach and, in females only,
      the mammary region. In both sexes, treatment-related tumors of the central
      nervous system (brain, spinal cord), ear canal, and gastrointestinal tract, and
      in females only, the mammary gland (intubation only) were observed in rats
      administered either 10 mg/kg per day by intubation or 100 ppm in drinking water.
      Animals from the intubation study had a substantially higher incidence of AN
      related site-specific tumors than did their drinking water study counterparts.
      While a similar spectrum of tumors was produced by both oral dosing regimens,
      there were some notable differences in organ-specific incidence of tumors.
      Astrocytomas of the brain and spinal cord were found at a higher incidence in
      those rats exposed continuously to AN administered in the drinking water versus
      bolus dosing by intubation. Conversely, a higher incidence of squamous cell
      carcinomas/papillomas of the forestomach and adenocarcinomas of the intestine
      and, in females only, carcinomas of the mammary gland were observed in high dose
      rats receiving AN by intubation. An increase in the degree of severity of
      forestomach hyperplasia was observed in all high dose groups of animals,
      irrespective of mode of administration. These effects were more pronounced, were
      correlated with a much higher incidence of forestomach tumors, and were
      identified earlier (12 months) in the intubation study in which there was direct
      tissue contact with a more concentrated AN solution. Elevations in epidermal
      cysts in high dose males and females in the intubation study and renal
      hyperplasia in high dose animals of both sexes in both studies may have a
      treatment relationship. All other clinical and microscopic findings were
      considered unremarkable. There were no discernable non-neoplastic effects
      attributable to treatment in groups of low dose male and female rats given AN by
      intubation at 0.1 mg/kg per day or 1 ppm in drinking water. The results of this
      study indicate a consistent spectrum of neoplastic and non-neoplastic effects
      produced by AN in the same rat strain, whether administered orally by bolus or by
      continuous dosing in the drinking water. While the spectrum of tumors and target
      organ toxicity produced was similar, bolus dosing clearly increased tumors
      associated with the gastrointestinal tract. Neoplasms found in several other
      tissues were most prominently displayed in groups of more continuously dosed
      rats.

PMID- 12044705
TI  - Chronic toxicity and oncogenic dose-response effects of lifetime oral
      acrylonitrile exposure to Fischer 344 rats.
AB  - Acrylonitrile (AN) was administered in the drinking water for approximately 2
      years to groups of 100 male and 100 female Fischer 344 rats at nominal
      concentrations of 1, 3, 10, 30, and 100 ppm. Two groups, each of 100 males and
      100 females, were used as untreated controls. Average daily intake was 0.1, 0.3,
      0.8, 2.5 or 8.4 mg AN per kg body weight per day, respectively, for treated male
      rats and 0.1, 0.4, 1.3, 3.7, or 10.9 mg AN per kg per body weight per day,
      respectively, for dosed females. Clinical biochemistry, interim necropsies, organ
      weights and microscopic evaluation of tissues and organs were performed on groups
      of ten rats per sex per group at months 6, 12, and 18 and at study termination.
      Females were sacrificed in the 24th month and males were terminated after 26
      months of dosing. A consistent decrease in survival, lower body weight and
      reduced water intake, as well as small reductions in hematological parameters,
      were observed in both sexes of the 100 ppm group. Elevated numbers of early
      deaths were observed in groups of males receiving 10 ppm AN and females receiving
      30 ppm AN. Organ:body weight ratios at various study intervals were consistently
      elevated in the high dose group and likely were related to lower body weights. At
      these same intervals, mean absolute weights were either comparable to controls or
      only slightly elevated and few changes in weight ratios were seen when organ
      weights were compared with brain weights. No biochemical changes suggested a
      treatment-related effect. An increase in urine specific gravity in 100 ppm male
      rats was reflective of a decrease in liquid intake at this level. The only
      significant non-neoplastic finding observed histologically was a dose-related
      increase in hyperplasia/hyperkeratosis in squamous cells of the forestomach in
      male and female rats given 3 ppm and higher AN. This observation correlated with
      the induction of treatment-related squamous cell tumors (papillomas and
      carcinomas) of the forestomach seen primarily in rats at 3 ppm AN and higher.
      Mammary gland carcinomas were observed only in female groups. Both sexes given 10
      ppm AN or more in their drinking water for their lifetime had astrocytomas of the
      brain/spinal cord and adenomas/carcinomas of the Zymbal's gland.

PMID- 12044706
TI  - Three-generation reproduction study of rats receiving acrylonitrile in drinking
      water.
AB  - Acrylonitrile, a high volume organic chemical, was tested for reproductive
      effects in a three generation drinking water study with two matings per
      generation. Sprague-Dawley rats were exposed to acrylonitrile in drinking water
      at 0, 100, or 500 ppm. This corresponds to 0, 11+/-5 and 37+/-10 mg/kg,
      respectively, for males and 0, 20+/-3 and 40+/-8 mg/kg per day for the females,
      respectively. Water consumption was reduced in F0 rats in the 100 and 500 ppm
      groups. At 500 ppm, acrylonitrile reduced body weight gain and food intake of the
      first generation parental rats (F0). These parameters were not investigated at
      subsequent generations. The pup survival (both viability and lactation indices)
      was reduced at the 500 ppm treatment level in both matings of all three
      generations. Fostering the 500 ppm pups onto untreated mothers following the
      second mating lessened mortality, suggesting a maternal effect consistent with
      decreased water consumption. There was no remarkable change in the reproductive
      capacity in any of matings in rats at the 100 ppm concentration. In contrast, in
      all three generations, the body weights of the pups of the 500 ppm treatment
      level were reduced on Day 21 at both matings. No adverse findings were observed
      in the tissues of a limited number of third generation weanlings (F3b) upon gross
      and microscopic evaluation. No effect on the sciatic nerve was evident among the
      adult female rats held for 20 weeks after weaning of the second litter. There was
      a dose-related effect of acrylonitrile on gross masses in female rats at each
      parental generation held 20 weeks after the weaning of the second litter.
      Histopathological evaluation of these dams showed an increase in astrocytomas and
      zymbal gland tumors.

PMID- 12044735
TI  - Children's predictions of consistency in people's actions.
AB  - Past research suggests that young children are often reluctant to generalize
      about people's behavior. Three experiments involving 102 4-5-year-olds, 84 7-8
      year-olds, and 107 adults explored the conditions under which inductive
      inferences about people are made. There was an age-based increase in propensity
      to predict consistency in psychological/intentional causal relations. Children
      often predicted change; people would behave differently in the future than they
      did in the past. Younger children limited predictions of consistency to non
      psychological contexts. Older children showed some appreciation of stable
      motivations (e.g. traits, preferences). The results are consistent with the
      hypothesis that children's theories of mind emphasize situational influences,
      with personal influences appearing in middle-childhood.

PMID- 12044736
TI  - Adjectives really do modify nouns: the incremental and restricted nature of early
      adjective acquisition.
AB  - By 24 months, most children spontaneously and correctly use adjectives. Yet prior
      laboratory research that has studied lexical acquisition in young children
      reports that children up to 3-years-old map novel adjectives to object properties
      only in very limited situations (Child Development 59 (1988) 411; Child
      Development 64 (1993) 1651; Child Development 71 (2000) 649; Developmental
      Psychology 36 (2000) 571; Child Development 69 (1998) 1313). In Experiments 1 and
      2 we introduced 36-month-olds (Experiment 1) and 24-month-olds (Experiment 2) to
      novel adjectives while providing rich referential and syntactic information to
      indicate what the novel words mean. Specifically, we used a given novel adjective
      to describe multiple familiar objects which shared a salient property; in
      addition we used the adjectives in full noun phrases, not in conjunction with
      pronouns. Under these conditions, both groups mapped novel adjectives onto object
      properties. In Experiment 3 we asked whether the rich referential information was
      responsible for the successful outcome of the previous two experiments; we
      introduced novel adjectives to 2- and 3-year-olds as in Experiments 1 and 2, but
      the adjectives modified nouns of vague (very general) reference ("one", or
      "thing"). Under these conditions the children failed. We suggest that young word
      learners require access to the taxonomy of the object type so that the relevant
      property can be identified. The taxonomically specific nouns of Experiments 1 and
      2 accomplish this, whereas the more general, semantically bleached nominals in
      Experiment 3 do not. Taken together with related findings in the literature,
      these findings favor an account of lexical acquisition in which layers of
      information become available incrementally, as a consequence of solving prior
      parts of the learning problem.

PMID- 12044737
TI  - Using relations within conceptual systems to translate across conceptual systems.
AB  - According to an "external grounding" theory of meaning, a concept's meaning
      depends on its connection to the external world. By a "conceptual web" account, a
      concept's meaning depends on its relations to other concepts within the same
      system. We explore one aspect of meaning, the identification of matching concepts
      across systems (e.g. people, theories, or cultures). We present a computational
      algorithm called ABSURDIST (Aligning Between Systems Using Relations Derived
      Inside Systems for Translation) that uses only within-system similarity relations
      to find between-system translations. While illustrating the sufficiency of a
      conceptual web account for translating between systems, simulations of ABSURDIST
      also indicate powerful synergistic interactions between intrinsic, within-system
      information and extrinsic information.

PMID- 12044738
TI  - The influence of attention on holistic face encoding.
AB  - We examined the influence of attention on the formation of holistic face
      representations using the composite effect (Perception 16 (1987) 747). In
      Experiment 1, stimuli composed of a face superimposed on a house were shown
      during encoding. Subjects delineated either the face or the house, thus
      manipulating attention away or toward the face. In Experiment 2, an intact face
      image was presented with letters scrolling from top to bottom. Subjects were
      asked to either ignore the letters or read them and decipher the words that they
      formed. Aligned and misaligned composites were shown at testing. Recognition
      performance was consistently better for misaligned than aligned stimuli,
      regardless of the allocation of attention during encoding. In Experiment 3, we
      show that the composite effect can be eliminated by a disruption in holistic
      processing at the time of encoding. We conclude that holistic encoding is one
      aspect of face analysis that occurs equally well with or without attention.

PMID- 12044739
TI  - Representation facilitates reasoning: what natural frequencies are and what they
      are not.
AB  - A good representation can be crucial for finding the solution to a problem.
      Gigerenzer and Hoffrage (Psychol. Rev. 102 (1995) 684; Psychol. Rev. 106 (1999)
      425) have shown that representations in terms of natural frequencies, rather than
      conditional probabilities, facilitate the computation of a cause's probability
      (or frequency) given an effect--a problem that is usually referred to as Bayesian
      reasoning. They also have shown that normalized frequencies--which are not
      natural frequencies--do not lead to computational facilitation, and consequently,
      do not enhance people's performance. Here, we correct two misconceptions
      propagated in recent work (Cognition 77 (2000) 197; Cognition 78 (2001) 247;
      Psychol. Rev. 106 (1999) 62; Organ. Behav. Hum. Decision Process. 82 (2000) 217):
      normalized frequencies have been mistaken for natural frequencies and, as a
      consequence, "nested sets" and the "subset principle" have been proposed as new
      explanations. These new terms, however, are nothing more than vague labels for
      the basic properties of natural frequencies.

PMID- 12044740
TI  - Chances and frequencies in probabilistic reasoning: rejoinder to Hoffrage,
      Gigerenzer, Krauss, and Martignon.
AB  - Do individuals unfamiliar with probability and statistics need a specific type of
      data in order to draw correct inferences about uncertain events? Girotto and
      Gonzalez (Cognition 78 (2001) 247) showed that naive individuals solve frequency
      as well as probability problems, when they reason extensionally, in particular
      when probabilities are represented by numbers of chances. Hoffrage, Gigerenzer,
      Krauss, and Martignon (Cognition 84 (2002) 343) argued that numbers of chances
      are natural frequencies disguised as probabilities, though lacking the properties
      of true probabilities. They concluded that we failed to demonstrate that naive
      individuals can deal with true probabilities as opposed to natural frequencies.
      In this paper, we demonstrate that numbers of chances do represent probabilities,
      and that naive individuals do not confuse numbers of chances with frequencies. We
      conclude that there is no evidence for the claim that natural frequencies have a
      special cognitive status, and the evolutionary argument that the human mind is
      unable to deal with probabilities.

PMID- 12044741
TI  - Prevalence of astigmatism in infant monkeys.
AB  - PURPOSE: Human infants exhibit a high prevalence of astigmatism. Although macaque
      monkeys are commonly used as animal models in experiments on early ocular growth
      and emmetropization, the prevalence of astigmatism in infant monkeys is
      unexplored. In this study we examine the prevalence and nature of astigmatism in
      infant monkeys. METHODS: Refractive and corneal astigmatism were measured in 132,
      2-5-week-old rhesus monkeys (Macaca mulatta) using cycloplegic retinoscopy and
      keratometry, respectively. Longitudinal measures of refractive development were
      obtained from 16 normal infants over the first 6 months of life. RESULTS: Infant
      monkeys exhibited a low prevalence of astigmatism. Approximately 90% of the 2-5
      week-old infants had <1.00 D of either refractive or corneal astigmatism. When
      refractive astigmatism was observed, it was well correlated with the direction
      and magnitude of corneal astigmatism. When corneal astigmatism was >1.00 D
      (n=20), it was predominantly against-the-rule in nature (70.0%). The infant
      monkeys that were followed longitudinally rarely showed significant astigmatic
      errors at any time during the observation period. When these infant monkeys
      exhibited significant astigmatism, it was usually transient and not present on
      subsequent measurements. CONCLUSIONS: Unlike human infants, infant monkeys
      exhibit relatively little astigmatism. The low prevalence of astigmatism during
      early development suggests that astigmatism does not provide an essential cue for
      vision-dependent eye growth in infant primates.

PMID- 12044742
TI  - Saccadic compression can improve detection of Glass patterns.
AB  - Around the time of saccadic eye movements, briefly presented stimuli are seen to
      be displaced from their real positions. The direction of the displacement is
      always towards the saccadic target, resulting in a compression of visual space
      (Nature 386 (1997) 598). To examine whether the compression may be used by the
      visual system to aid performance, we measured sensitivity for detecting
      horizontal and vertical Glass patterns around the time of saccades. Sensitivity
      to widely spaced horizontal Glass patterns improved slightly during the period
      just prior to making a horizontal saccade, while sensitivity to vertical patterns
      was impaired by the saccade. The results provide further evidence for compression
      in the direction of the saccade at saccadic onset, and show that it does not only
      affect the apparent position of visual stimuli, but can also improve performance
      on a visual task.

PMID- 12044743
TI  - Individual differences in chromatic (red/green) contrast sensitivity are
      constrained by the relative number of L- versus M-cones in the eye.
AB  - Many previous studies have shown that the relative number of long-wavelength
      selective (L) versus medium-wavelength-selective (M) cones in the eye influences
      spectral sensitivity revealed perceptually. Here, we hypothesize that the L:M
      cone ratio should also influence red/green chromatic contrast sensitivity. To
      test this, in each subject we derived an estimate of L:M ratio based on her
      red/green equiluminance settings (obtained with heterochromatic flicker
      photometry), and measured both red/green chromatic and luminance contrast
      sensitivity at different spatial and temporal frequencies. Factor analysis was
      applied to the data in order to reveal covariance between conditions. As
      expected, chromatic and luminance contrast sensitivity were found to be
      independent of one another, and no relationship was observed between L:M ratio
      and luminance contrast sensitivity. However, a significant relationship was
      observed between L:M ratio and chromatic contrast sensitivity, wherein subjects
      possessing the most symmetrical L:M cone ratios (i.e., near 1:1) appear to
      possess the relatively greatest chromatic contrast sensitivity. This relationship
      can be accounted for by a simple model based on the notion of random L- and M
      cone inputs to the center and surround receptive fields of chromatic (L-M)
      mechanisms.

PMID- 12044744
TI  - Suppressive and facilitatory spatial interactions in amblyopic vision.
AB  - Amblyopic vision is characterized by reduced spatial resolution, and inhibitory
      spatial interactions ("crowding") that extend over long distances. The present
      paper had three goals: (1) To ask whether the extensive crowding in amblyopic
      vision is a consequence of a shift in the spatial scale of analysis. To test this
      we measured the extent of crowding for targets that were limited in their spatial
      frequency content, over a large range of target sizes and spatial frequencies.
      (2) To ask whether crowding in amblyopic vision can be explained on the basis of
      contrast masking by remote flanks. To test this hypothesis we measured and
      compared crowding in a direction-identification experiment with masking by remote
      flanks in a detection experiment. In each of the experiments our targets and
      flanks were comprised of Gabor features, thus allowing us to control the feature
      contrast, spatial frequency and orientation. (3) To examine the relationship
      between the suppressive and facilitatory interactions in amblyopic contrast
      detection and "crowding". Our results show that unlike the normal fovea [Levi,
      Klein, & Hariharan, Journal of Vision 2 (2002a) 140] crowding in amblyopia is
      neither scale invariant, nor is it attributable to simple contrast masking.
      Rather, our results suggest that suppressive spatial interactions in amblyopic
      vision extend over larger distances than in normal foveal vision, similar to
      peripheral vision of non-amblyopic observers [Levi, Hariharan, & Klein, Journal
      of Vision 2 (2002b) 167], for targets of the same size. Observers can easily
      detect the features that comprise our targets (Gabor patches) under conditions
      where crowding is strong. Thus, our speculation is that crowding occurs because
      the target and flanks are combined or pooled at a second stage that is coarse in
      the amblyopic visual system, following the stage of feature extraction. In
      amblyopic vision, this pooling takes place over a large spatial distance.

PMID- 12044745
TI  - Chromatic input to motion processing in the absence of attention.
AB  - While several previous psychophysical and neurophysiological studies have
      demonstrated chromatic (red/green) input to motion processing, the nature of this
      input is still a matter of debate. In particular, recent controversy has
      developed regarding whether chromatic motion processing relies on lower-level
      processes [J. Neurosci. 14 (1994) 4854; 19 (1999) 6571] versus higher-level,
      attention- or salience-based mechanisms [Science 257 (1992) 1563; Proc. Natl.
      Acad. Sci. 96 (1999a) 8289; 96 (1999b) 15374]. In this study, we investigated the
      degree to which chromatic motion is influenced by attentional mechanisms by
      employing a dual-task paradigm, which allowed us to compare the strength of
      chromatic motion under conditions of poor versus full attention. Here, we found
      that for equiluminant red/green gratings, chromatic motion processing is as
      robust in poor, as in full, attention conditions. This lack of an attentional
      effect suggests that chromatic motion processing must rely, at least in part, on
      lower-level (i.e., pre-attentive) motion mechanisms. For non-equiluminant (e.g.,
      red brighter than green) gratings, however, attention significantly modulates
      chromatic motion strength. Possible explanations for this latter result are
      discussed in the context of inherent salience differences between the bright-red
      and dim-green stripes of the heterochromatic grating.

PMID- 12044746
TI  - Visual perception of planar orientation: dominance of static depth cues over
      motion cues.
AB  - We measured the ability to report the tilt (direction of maximal slope) of a
      plane under monocular viewing conditions, from static depth cues (square grid
      patterns) and motion parallax (small rotations of the plane about a
      frontoparallel axis). These two cues were presented separately, or
      simultaneously. In the latter case they specified tilts that were either
      collinear (coherent case) or orthogonal (conflict case). The field of view was
      small (8 degrees) or large (60 degrees). In small field, for motion parallax, the
      reported tilt depends strongly on the orientation of the plane relative to the
      rotation axis, being totally ambiguous when tilt is collinear with the rotation
      axis. In contrast, in large field, the reported tilt depends little on this
      variable, and is accurately specified by motion cues. In both cases static cues
      strongly dominated the tilt reports. Hence static grid patterns constitute robust
      tilt cues, which can dominate contradictory tilt indications from motion
      parallax, and should be considered as essential for the visual orientation during
      locomotion, or the immersion in virtual reality environments.

PMID- 12044747
TI  - Spatial frequency tuning of the Ouchi illusion and its dependence on stimulus
      size.
AB  - This study investigated the effects of the stimulus size on the spatial frequency
      tuning of the Ouchi illusion, which is an illusory sliding motion perceived in a
      checkerboard pattern of rectangular elements that is surrounded by a checkerboard
      pattern of orthogonally oriented elements. Two experiments were conducted to
      measure the perceived strength of illusion. The optimal size of the inner pattern
      increased proportionally with check size. In contrast, the optimal check size
      increased with the size of the inner pattern but not proportionally, and the
      range of increase was relatively small. The optimal fundamental spatial frequency
      was lower for a larger stimulus both for checkerboard patterns and simpler
      sinusoidal grating patterns, but there were differences in the tuning curves for
      the two types of stimuli. These results support the idea that two processes
      underlie the Ouchi illusion; one computes the local motion direction, and the
      other integrates motion signals across space for surface segmentation. For the
      checkerboard and grating stimuli, the former process may be different while the
      latter can be shared.

PMID- 12044748
TI  - Symmetry detection and visual attention: a "binary-map" hypothesis.
AB  - Recent research suggests that human symmetry-detection mechanisms cannot
      simultaneously compare different colors across the axis of symmetry (Nature 399
      (1999) 115). In the present study, observers were required to judge symmetry in
      arrays composed of elements varying not only in color, but also in size, spatial
      frequency and orientation. In every case, response times increased with the
      number of different levels of a given feature. It is proposed that this increase
      reflects a sequential strategy whereby coarse "binary maps" are created by
      attentional filtering, and the symmetry of each map is then checked. Experiment 2
      required observers to detect "pseudo-symmetry" (symmetry in feature values
      defined relative to an arbitrary featural boundary); the ease with which this
      task was accomplished supported the binary map hypothesis. The results suggest
      that (1) symmetry detection is spatially imprecise, and (2) attentional gating
      can operate prior to symmetry detection in the visual pathway.

PMID- 12044749
TI  - Collinearity improves alignment. Response to Keeble and Hess (1998).

PMID- 12044750
TI  - Idiosyncratic left-right asymmetries of saccadic latencies: examination in a gap
      paradigm.
AB  - Subjects were given reflexive- and voluntary-saccade tasks using five different
      gap intervals (0-500 ms) between the fixation point offset and the target onset
      and an overlap paradigm (i.e., the fixation point remained on during the target
      presentation). In the first experiment, targets were monocularly presented, and
      the latencies of reflexive saccades to a peripheral target were compared between
      the left and right visual fields in which targets were presented. The data
      averaged over subjects did not show a significant difference of saccade latencies
      between the two visual fields. However, individual subjects showed strong
      left/right asymmetries of saccade latencies: six out of the 12 subjects that
      participated made a saccade more rapidly to the right than to the left, and two
      other subjects showed the reverse result. In these cases, the left/right
      asymmetry was observed on both gap and overlap trials. The saccade latencies were
      not affected by the hemiretina to which a target was projected. The second
      experiment was conducted to identify conditions under which the left/right
      asymmetry can be reproduced. For this purpose, five subjects were given both
      reflexive-saccade and voluntary-saccade tasks. In the latter task, a cue stimulus
      for generating saccades was given at the central fixation point. Regardless of
      whether saccades were made reflexively or voluntarily, and whether the targets
      were viewed monocularly or binocularly, each subject showed the same pattern of
      left/right asymmetries of saccade latencies. The results were interpreted as
      showing that a visuo-spatial attentional bias specific to individual subjects is
      involved in generating idiosyncratic left/right asymmetries of saccade latencies.

PMID- 12044751
TI  - Eye movements in iconic visual search.
AB  - Visual cognition depends critically on the moment-to-moment orientation of gaze.
      To change the gaze to a new location in space, that location must be computed and
      used by the oculomotor system. One of the most common sources of information for
      this computation is the visual appearance of an object. A crucial question is:
      How is the appearance information contained in the photometric array is converted
      into a target position? This paper proposes a such a model that accomplishes this
      calculation. The model uses iconic scene representations derived from oriented
      spatiochromatic filters at multiple scales. Visual search for a target object
      proceeds in a coarse-to-fine fashion with the target's largest scale filter
      responses being compared first. Task-relevant target locations are represented as
      saliency maps which are used to program eye movements. A central feature of the
      model is that it separates the targeting process, which changes gaze, from the
      decision process, which extracts information at or near the new gaze point to
      guide behavior. The model provides a detailed explanation for center-of-gravity
      saccades that have been observed in many previous experiments. In addition, the
      model's targeting performance has been compared with the eye movements of human
      subjects under identical conditions in natural visual search tasks. The results
      show good agreement both quantitatively (the search paths are strikingly similar)
      and qualitatively (the fixations of false targets are comparable).

PMID- 12044752
TI  - Action-perception dissociation in response to target acceleration.
AB  - The purpose of this study was to investigate whether information about the
      acceleration characteristics of a moving target can be used for both action and
      perception. Also of interest was whether prior movement experience altered
      perceptual judgements. Participants manually intercepted targets moving with
      various acceleration, velocity and movement time characteristics. They also made
      perceptual judgements about the acceleration characteristics of these targets
      either with or without prior manual interception experience. Results showed that
      while aiming kinematics were sensitive to the acceleration characteristics of the
      target, participants were only able to perceptually discriminate the velocity
      characteristics of target motion, even after performing interceptive actions to
      the same targets. These results are discussed in terms of a two channel (action
      perception) model of visuomotor control.

PMID- 12044753
TI  - Abnormalities of the long flash ERG in congenital stationary night blindness of
      the Schubert-Bornschein type.
AB  - We investigated abnormalities of the retinal cone ON- and OFF-pathways in 24
      males with Schubert-Bornschein congenital stationary night blindness (CSNB).
      Substantial differences were found between both CSNB types. In incomplete type, a
      , b- and d-waves were reduced and delayed, whereas in complete type only the b
      wave showed significant changes. Oscillatory potentials (OPs) were not
      discernible from noise in incomplete CSNB and showed significant peak alterations
      of the ON-OPs only in complete CSNB. In the complete CSNB type, the ON pathway
      appeared to be mainly affected. In the incomplete CSNB form marked involvement of
      both the ON and the OFF pathways was noted.

PMID- 12044754
TI  - Short-term temporal recruitment in structure from motion.
AB  - Temporal integration was investigated in the minimal conditions necessary to
      perform a structure-from-motion (SFM) task. Observers were asked to discriminate
      three-dimensional (3D) surface orientations in conditions in which the stimulus
      displays simulated velocity fields providing, in each frame transition, either
      sufficient (3 moving dots) or insufficient information (1 or 2 moving dots) to
      perform the task. When only two moving dots were shown in each frame transition
      of the stimulus displays (Experiment 1), we found that performance decreased as
      dot-lifetime increased. A facilitation effect of the overall display duration was
      also found. The negative effect of dot-lifetime on performance contrasts with
      what found in Experiment 2 with three dots in each frame transition, where
      performance improved with increasing dot-lifetime up to 170 ms, and then reached
      a plateau. Finally, for an optimal dot-lifetime of 150 ms, we found that
      performance was still above chance when each frame transition specified the
      motion of only one dot (Experiment 3). These results indicate that temporal
      recruitment alone can support the recovery of 3D information from sparse motion
      signals, thus providing a strong indication for the importance of temporal
      integration in the perceptual analysis of the optic flow. Our results reveal,
      moreover, that temporal integration in SFM has different characteristics,
      depending on whether, in each frame transition, the stimulus displays provide
      either sufficient (3 or more moving dots) or insufficient information (1 or 2
      moving dots) to specify the higher-order properties of the optic flow necessary
      for 3D surface recovery.

PMID- 12044755
TI  - Binocular integration of partially occluded surfaces.
AB  - Normal binocular vision can provide a view of an object partially occluded so
      that no part of it is seen by both eyes but all of it is seen by one or other
      eye. We used two-dimensional filtered noise textures to explore the conditions
      under which the visual system can piece together the monocular fragments of such
      occluded surfaces. When the fragments seen by left and right eyes are drawn from
      a continuous texture with strong horizontal correlation, observers see coherent
      surfaces reliably located in depth. When textures are discontinuous or have
      weaker horizontal correlation, or the left and right eyes' views represent
      unnatural depth relationships, no coherent surface is perceived, and binocular
      rivalry ensues. The discovery of coherent surfaces under our conditions seems to
      reflect the operation of a high-level integration process, failures of which
      drive rivalry.

PMID- 12044756
TI  - Directional performance in motion transparency.
AB  - Motion transparency provides a challenging test case for our understanding of how
      visual motion, and other attributes, are computed and represented in the brain.
      However, previous studies of visual transparency have used subjective criteria
      which do not confirm the existence of independent representations of the
      superimposed motions. We have developed measures of performance in motion
      transparency that require observers to extract information about two motions
      jointly, and therefore test the information that is simultaneously represented
      for each motion. Observers judged whether two motions were at 90 degrees to one
      another; the base direction was randomized so that neither motion taken alone was
      informative. The precision of performance was determined by the standard
      deviations (S.D.s) of probit functions fitted to the data. Observers also made
      judgments of orthogonal directions between a single motion stream and a line, for
      one of two transparent motions against a line and for two spatially segregated
      motions. The data show that direction judgments with transparency can be made
      with comparable accuracy to segregated (non-transparent) conditions, supporting
      the idea that transparency involves the equivalent representation of two global
      motions in the same region. The precision of this joint direction judgment is,
      however, 2-3 times poorer than that for a single motion stream. The precision in
      directional judgment for a single stream is reduced only by a factor of about 1.5
      by superimposing a second stream. The major effect in performance, therefore,
      appears to be associated with the need to compute and compare two global
      representations of motion, rather than with interference between the dot streams
      per se. Experiment 2 tested the transparency of motions separated by a range of
      angles from 5 degrees to 180 degrees by requiring subjects to set a line matching
      the perceived direction of each motion. The S.D.s of these settings demonstrated
      that directions of transparent motions were represented independently for
      separations over 20 degrees. Increasing dot speeds from 1 to 10 deg/s improved
      directional performance but had no effect on transparency perception.
      Transparency was also unaffected by variations of density between 0.1 and 19
      dots/deg(2)

PMID- 12044757
TI  - Perceptual learning of luminance contrast detection: specific for spatial
      frequency and retinal location but not orientation.
AB  - Performance of a wide range of simple visual tasks improves with practice. Here
      we ask whether such learning occurs for the fundamental visual task of luminance
      contrast detection. In two experiments we find that contrast sensitivity
      increases following extensive practice at detecting briefly presented sinusoidal
      luminance gratings and that learning is maintained after six months. Learning is
      spatial frequency tuned, specific to retinal location and can be specific to one
      eye, but is not selective for orientation. The selectivity of learning implies
      that it is based on plasticity in early visual, as opposed to central cognitive,
      processing mechanisms.

PMID- 12044758
TI  - Thalamocortical dynamics of the McCollough effect: boundary-surface alignment
      through perceptual learning.
AB  - This article further develops the FACADE neural model of 3-D vision and figure
      ground perception to quantitatively explain properties of the McCollough effect
      (ME). The model proposes that many ME data result from visual system mechanisms
      whose primary function is to adaptively align, through learning, boundary and
      surface representations that are positionally shifted due to the process of
      binocular fusion. For example, binocular boundary representations are shifted by
      binocular fusion relative to monocular surface representations, yet the
      boundaries must become positionally aligned with the surfaces to control
      binocular surface capture and filling-in. The model also includes perceptual
      reset mechanisms that use habituative transmitters in opponent processing
      circuits. Thus the model shows how ME data may arise from a combination of
      mechanisms that have a clear functional role in biological vision. Simulation
      results with a single set of parameters quantitatively fit data from 13
      experiments that probe the nature of achromatic/chromatic and monocular/binocular
      interactions during induction of the ME. The model proposes how perceptual
      learning, opponent processing, and habituation at both monocular and binocular
      surface representations are involved, including early thalamocortical sites. In
      particular, it explains the anomalous ME utilizing these multiple processing
      sites. Alternative models of the ME are also summarized and compared with the
      present model.

PMID- 12044759
TI  - Attention shifts to salient targets.
AB  - To investigate the role of salience in fast visual search, time courses for the
      detection and identification of salient targets were measured in six subjects,
      using texture-like line arrays. Single lines were made salient from luminance
      contrast, motion contrast, or by an added circular cue that is known to attract
      focal attention. Three major findings are reported: (1) Identification of target
      orientation required longer presentations than detection of the saliency effect
      itself, consistent with the model that target salience attracts focal attention
      for target analysis. (2) Different saliency mechanisms produced similar effects,
      suggesting that salience from feature contrast is functionally equivalent to
      salience evoked from a visual cue. (3) Circular cues were most effective when
      presented close to the target; performance in target identification decreased
      when the diameter was enlarged so that the cue was presented farther away and on
      a different spatial scale. All together, these findings suggest that popout
      targets in visual search may be detected fast and independent of set size because
      (a) they are salient and attract focal attention, and (b) their salience is
      produced on the same spatial scale and at the same location in the visual field
      where target properties are encoded.

PMID- 12044760
TI  - The cyclopean eye in vision: the new and old data continue to hit you right
      between the eyes.
AB  - We argue against recent claims by Erkelens and van Ee (Vision Res., in press) and
      by Erkelens (Vision Res. 40 (2000) 2411) that "the concept of the cyclopean eye
      is em leader always irrelevant as far as vision is concerned" (p. 1157)
      [corrected] and that "perceived direction during monocular viewing is based on
      the signals of the viewing eye only" (p. 2411), respectively. In Experiment 1, we
      presented a pair of small lights on a visual axis and measured the absolute
      visual direction of the near light with reference to different parts of the face.
      The near light appeared in front of the bridge of the nose or very near it,
      contrary to what was expected from Erkelens and van Ee's claim that monocular
      stimuli are seen in their correct locations. In Experiment 2, we replicated
      Erkelens' experiments with measurements of phoria and analyses of eye movements.
      The results confirmed his finding that the cyclopean illusion occurred rarely in
      the monocular condition, but our phoria and eye movement data provided the basis
      for a very different interpretation. Our data show that the oculomotor signal in
      his particular monocular condition was considerably weaker than in his binocular
      condition; therefore, the rarity of the monocular cyclopean illusion is not
      surprising. Moreover, since both claims above are based on an over-generalization
      of the results of Erkelens' study, neither claim is persuasive.

PMID- 12044761
TI  - Head-free reading of horizontally and vertically arranged texts.
AB  - Parameters of eye and head movements and their coordination in reading
      horizontally and vertically arranged texts were compared. Reading was faster for
      horizontally arranged than for vertically arranged texts by 24%, primarily due to
      larger gaze amplitude for horizontal reading, and thus smaller numbers of
      saccades and fixations. The higher velocity of gaze saccades for given amplitudes
      in horizontal than vertical reading also contributed to the difference in reading
      speed. The horizontal bias in reading is at least partly due to the oculomotor
      system, because the higher velocity for given amplitude of horizontal saccade was
      also observed in a control experiment devoid of lexical load, in which a
      sequentially stepping laser target was tracked. The analysis of instantaneous
      phase of eye and head movements with a new metric derived by the Hilbert
      transform suggests that eye and head coupling is stronger for vertical than for
      horizontal direction in both reading and laser-tracking tasks. These results,
      combined with previous evidence that text familiarity modulates the timing and
      strength of head movement commands with respect to eye movements (Vis. Res. 39
      (1999) 3761), indicate that the coupling strength between eye and head movements
      is variable depending on the direction of gaze shift and cognitive context.

PMID- 12044762
TI  - Hemianopic visual field defects elicit hemianopic scanning.
AB  - Previous explanations for the variability in success of compensating for
      homonymous hemianopia (HH) has been in terms of extent of the brain injury. In
      using on-line eye movement registrations, we simulated HH in 16 healthy subjects
      and compared their scanning performance on a dot counting task to their own
      "normal" condition and to real HH patients' performance. We evidenced clear
      parallels between simulated and real HH, suggesting that hemianopic scanning
      behaviour is primarily visually elicited, namely by the visual field defect, and
      not by the additional brain damage. We further observed age-related processes in
      compensating for the HH.

PMID- 12044763
TI  - Heart and breast muscle mitochondrial dysfunction in pulmonary hypertension
      syndrome in broilers (Gallus domesticus).
AB  - This study was conducted to determine function and defects in electron transport
      in muscle mitochondria of meat chickens (broilers) with pulmonary hypertension
      syndrome (PHS). The respiratory control ratio (RCR, indicative of respiratory
      chain coupling) was higher in the control than in PHS breast and heart muscle
      mitochondria, but there were no differences in the ADP/O (an index of oxidative
      phosphorylation). Sequential additions of ADP improved the RCR in the control
      breast muscle mitochondria and the ADP/O in PHS breast and heart muscle
      mitochondria. Basal hydrogen peroxide production, (an indicator of electron
      leak), was higher in PHS breast and heart muscle mitochondria than in controls
      and differences in electron leak in PHS mitochondria were magnified by inhibiting
      electron transport at Complex I and III (cyt b(562)). Complex I activity was
      lower in PHS heart mitochondria but there was no difference in Complex II
      activity. Thus, compared to controls, PHS mitochondria exhibited site-specific
      defects in electron transport within Complex I and III that could contribute to
      lower respiratory chain coupling. Additionally, it appears that healthy broilers
      may exhibit higher basal levels of electron leak compared to other avian species.
      Together, these findings provide insight into inefficient cellular use of oxygen
      that may contribute to the development of PHS in broilers.

PMID- 12044764
TI  - Cytometric, morphologic and enzymatic characterisation of haemocytes in Anodonta
      cygnea.
AB  - The haemocytes in bivalve mussels are involved in many processes such as lesion
      repair, shell repair, elimination of small particles and toxic substances. In
      Anodonta cygnea there are two categories of haemolymph cells, the granulocytes
      and hyalinocytes. Two groups of cells were identified by flow cytometry and
      morphological studies: one with larger size and granularity representing 75%, and
      another group of cells (25%) which were approximately half the size. The
      cytochemical reactions showed peroxidase activity in the larger cells and a weak
      prophenoloxidase activity in the smaller cells. These characteristics suggest
      that the most common haemocytes are granulocytes and hyalinocytes are less
      common. Enzymatic studies showed clear activities of few enzymes in different
      compartments of the mantle. Both haemocytes presented significant variations for
      alpha-manosidase and beta-glucurosidase activities depending on the acid or
      alkaline pH. Almost all were sensitive to the pH changes, mainly the beta
      galactosidase in the haemolymph plasma. On the contrary, the same enzymatic
      analysis in the extrapallial elements showed more stabilised activities. The
      simulation of acidic and alkaline condition with the observation of significant
      morphological and enzymatic activity changes, allow us to speculate some
      functional role, mainly in the haemolymph elements. The granulocytes may be
      speculated to have intense involvement in the digestion of small residues with
      the formation of calcareous stores while the hyalinocytes are more responsible
      for the elimination of soluble cytotoxic compounds.

PMID- 12044765
TI  - Metabolic response of cerambycid beetle (Morimus funereus) larvae to starvation
      and food quality.
AB  - The response of xylophagous Morimus funereus larvae to a direct change of diet
      demonstrated that the larvae from nutrient-poor substrates, e.g. oak, are very
      sensitive to such a change. Depending on dietary protein quality and quantity, an
      increase of proteolytic activity, i.e. an intensified protein metabolism
      accompanied by changes in body mass gain, was observed. At the same time,
      amylolytic activity was usually decreased. In the larvae reared on Robert's diet,
      sensitivity to the switch in diet was lower at the level of proteolytic enzymes
      that remained at the control level, while amylolytic activity was elevated. If
      the switch to a new diet was preceded by 7-day-starvation that disturbed
      nutritional homeostasis, the response of the larvae was similar to that recorded
      upon a direct switch only after short-term feeding (24 h) upon starvation.
      Differences in the response to changes in the diet of the larvae from nature,
      those reared under laboratory conditions and those of different physiological
      status could be ascribed to plasticity in the expression of the genes coding for
      proteases and their isoenzymes, as well as to the multi-functionality of some
      neurosecretory neurons, synthetic products that participate in the regulation of
      digestive enzyme activities.

PMID- 12044766
TI  - Spermatogenesis and related plasma androgen levels in Atlantic halibut
      (Hippoglossus hippoglossus L.).
AB  - Spermatogenesis in male Atlantic halibut (Hippoglossus hippoglossus L.) was
      investigated by sampling blood plasma and testicular tissue from 15-39-month-old
      fish. The experiment covered a period in which all fish reached puberty and
      completed sexual maturation at least once. The germinal compartment in Atlantic
      halibut testis appears to be organized in branching lobules of the unrestricted
      spermatogonial type, because spermatocysts with spermatogonia were found
      throughout the testis. Spermatogenesis was characterized histologically, and
      staged according to the most advanced type of germ cell present: spermatogonia
      (Stage I), spermatogonia and spermatocytes (Stage II), spermatogonia,
      spermatocytes and spermatids (Stage III), spermatogonia, spermatocytes,
      spermatids and spermatozoa (Stage IV), and regressing testis (Stage V). Three
      phases could be distinguished: first, an initial phase with low levels of
      circulating testosterone (T; quantified by RIA) and 11-ketotestosterone (11-KT;
      quantified by ELISA), spermatogonial proliferation, and subsequently the
      initiation of meiosis marked by the formation of spermatocytes (Stage I and II).
      Secondly, a phase with increasing T and 11-KT levels and with haploid germ cells
      including spermatozoa present in the testis (Stage III and IV). Thirdly, a phase
      with low T and 11-KT levels and a regressing testis with Sertoli cells displaying
      signs of phagocytotic activity (Stage V). Circulating levels of 11-KT were at
      least four-fold higher than those of T during all stages of spermatogenesis.
      Increasing plasma levels of T and 11-KT were associated with increasing
      testicular mass throughout the reproductive cycle. The absolute level of, or the
      relation between, testis growth and circulating androgens were not significantly
      different in first time spawners compared to fish that underwent their second
      spawning season. These results provide reference levels for Atlantic halibut
      spermatogenesis.

PMID- 12044767
TI  - Comparison of the soluble matrices of the calcitic prismatic layer of Pinna
      nobilis (Mollusca, Bivalvia, Pteriomorpha).
AB  - The calcitic prisms of the outer layer of the shell of Pinna nobilis, surrounded
      by thick organic walls, contain a soluble intracrystalline matrix. The structure
      and composition of the outer interprismatic walls are not well known. The current
      viewpoint is they are composed of an insoluble matrix. Another thick organic
      structure, the interlamellar sheet of the nacreous layer, is composed of
      insoluble and soluble matrices. The composition of two sets of soluble organic
      matrices from the calcitic layer of Pinna nobilis, extracted with and without the
      organic walls are compared. According to the various analyses (SEM and AFM, UV
      and FTIR spectrometry, HPLC, electrophoreses, XANES), the main characteristics of
      the two matrices are similar, but not identical. Thus, the organic walls contain
      soluble components. However, the three-layered structure of the interlamellar
      sheet of the nacreous layer has not been observed.

PMID- 12044768
TI  - A newly developed ELISA showing the effect of environmental stress on levels of
      hsp86 in Cherax quadricarinatus and Penaeus monodon.
AB  - The induction of hsps by stress in Cherax quadricarinatus and Penaeus monodon was
      investigated using SDS-PAGE, Western blotting and ELISA techniques. Western
      blotting showed the presence of an immuno-reactive protein to mouse alpha-human
      hsp70 IgG1 monoclonal antibody at a mass of 86 kDa (hsp86) in pleopod samples but
      was not sensitive enough to detect differences in response to stress. An enzyme
      linked immunosorbent assay (ELISA) was developed using this antibody for the
      detection of hsp86 in the pleopods of C. quadricarinatus and P. monodon. Using
      this assay, significantly higher levels of hsp86 were detected in hyperthermally
      stressed C. quadricarinatus (21 to 70 g) and P. monodon (14 to 32 g) and
      hypoosmotically stressed P. monodon (14 to 32 g). Male C. quadricarinatus and P.
      monodon were thermally stressed with an increase in temperature from 24 to 33
      degrees C for a period of 2 h then a recovery period of 6 h. SDS-PAGE gels of
      thermally stressed C. quadricarinatus and P. monodon samples revealed an increase
      in protein band intensity at 97 kDa (C. quadricarinatus) and 43 and 35 kDa in P.
      monodon. A 25 kDa mass protein was induced in C. quadricarinatus when thermally
      stressed. P. monodon were osmotically stressed with a decrease from 31 to 15 ppt
      for 2 h with a recovery of 6 h. SDS-PAGE gels revealed increased intensity of
      bands at 35 and 43 kDa and a 100 kDa band was induced demonstrating a wide range
      response of protein profile to stress in these species. SDS-PAGE gels of both
      species investigated also revealed an apparent reduction in band intensity of the
      haemocyanin subunits in stressed samples. The ELISA described here constitutes
      the first quantitative assay for the detection of a hsp in crustaceans and the
      following investigations are believed to be the first to describe the response of
      hsps to stress in C. quadricarinatus and P. monodon. In doing so, they provide a
      sound basis for future studies of the role of hsps in physiological functions in
      commercially cultured crustaceans.

PMID- 12044769
TI  - Postnatal ontogeny of kinetics of porcine jejunal brush border membrane-bound
      alkaline phosphatase, aminopeptidase N and sucrase activities.
AB  - Our objectives were to determine postnatal changes in the maximal enzyme activity
      (V(max)) and enzyme affinity (K(m)) of jejunal mucosal membrane-bound alkaline
      phosphatase, aminopeptidase N and sucrase using a porcine model which may more
      closely resemble the human intestine. Jejunal brush border membrane was prepared
      by Mg(2+)-precipitation and differential centrifugation from pigs of suckling (8
      days), weaning (28 days), post-weaning (35 days) and adult (70 days) stages. p
      Nitrophenyl phosphate (0-8 mM), L-alanine-p-nitroanilide hydrochloride (0-28 mM)
      and sucrose (0-100 mM) were used in alkaline phosphatase, aminopeptidase N and
      sucrase kinetic measurements. V(max) of alkaline phosphatase was the lowest in
      the adult (4.27 micromol.mg(-1) protein.min(-1)), intermediate in the suckling
      (9.75 micromol.mg(-l) protein.min(-l)) and the highest in the weaning and post
      weaning stage (12.83 and 10.40 micromol.mg(-l) protein.min(-l)). K(m) of alkaline
      phosphatase was high in the suckling and weaning stages (5.14 and 9.93 mM) and
      low in the adult (0.66 mM). V(max) of aminopeptidase N was low in the suckling
      (7.04 micromol.mg protein(-1).min(-1)) and high in the post-weaning stage (13.36
      micromol.mg(-l) protein.min(-l)). K(m) of aminopeptidase N was the highest in the
      two weaning stages (2.96 and 3.39 mM), intermediate in the adult (2.33 mM) and
      the lowest in the suckling stage (1.66 mM). V(max) of sucrase increased from the
      suckling to the adult (0.48-1.30 micromol.mg(-l) protein.min(-l)). K(m) of
      sucrase ranged from 11.19 to 16.57 mM. There are dramatic postnatal developmental
      changes in both the maximal enzyme activity and enzyme affinity of jejunal brush
      border membrane-bound alkaline phosphatase, aminopeptidase N and sucrase in the
      pig.

PMID- 12044770
TI  - Dietary and seasonal effects on the dorsal meat lipid composition of Japanese
      (Silurus asotus) and Thai catfish (Clarias macrocephalus and hybrid Clarias
      macrocephalus and Clarias galipinus).
AB  - The effects of dietary lipids and seasonal variation on the lipids of wild and
      cultured catfish (Japanese catfish, Silurus asotus; Thai catfish, Clarias
      macrocephalus and hybrid Clarias macrocephalus x Clarias galipinus) were
      determined by analysis of the lipid content and fatty acid composition of their
      dorsal meat. The predominant fatty acids of dorsal meat were 16:0, 18:1n-9, 18:2n
      6, 20:4n-6 (arachidonic acid, AA), and 22:6n-3 (docosahexaenoic acid, DHA). The
      DHA content in the diet of Japanese catfish was higher than that in the diet of
      Thai catfish, and this was reflected in the dorsal meat of the Japanese catfish,
      which had a remarkably high percentage of DHA compared with the meat of the Thai
      catfish. Cultured Japanese catfish had a higher percentage of 18:2n-6 than Thai
      fish and a lower percentage of AA in winter than in summer season. There were
      also seasonal variations in the percentage of n-6 fatty acids in Japanese
      catfish. In summer, the fatty acid composition of the cultured Japanese catfish
      was similar to that of the wild catfish. These fatty acid changes in the lipid
      classes, triacylglycerol, phosphatidylcholine and phosphatidylethanolamine were
      similar to those observed for total lipids. These results indicate that the
      percentage of DHA in the dorsal meat of catfish is influenced by dietary fatty
      acid, and it may be that it can be increased in cultivated fish by administering
      a diet containing a large amount of DHA.

PMID- 12044771
TI  - Octanoate inhibits very low-density lipoprotein secretion in primary cultures of
      chicken hepatocytes.
AB  - The effects of octanoate, a medium-chain fatty acid, on very low-density
      lipoprotein (VLDL) secretion in primary cultures of chicken hepatocytes were
      compared with those of palmitate. Palmitate added to the incubation media at
      concentrations up to 0.36 mM increased intracellular triacylglycerol (TG)
      accumulation and VLDL-TG secretion in a concentration-dependent manner, whereas
      the addition of octanoate alone (0.21-0.6 mM) did not change these parameters.
      VLDL-TG secretion from hepatocytes cultured in media to which 0.6 or 1.0 mM
      octanoate had been added in the presence of 0.21 mM palmitate was significantly
      lower than that obtained under control incubation conditions (0.21 mM palmitate
      only). The addition of 1.0 mM octanoate to the incubation media with or without
      0.21 mM palmitate decreased VLDL apolipoprotein B (apoB) secretion. These results
      demonstrate that the addition of octanoate to primary cultures of chicken
      hepatocytes reduces VLDL secretion in respect of both TG and apoB secretion. It
      is suggested that medium-chain fatty acids are a factor modulating VLDL
      secretion, which plays a key role in fat deposition in chickens.

PMID- 12044772
TI  - mRNA expression of pancreatic enzyme precursors and estimation of protein
      digestibility in first feeding larvae of the Japanese flounder, Paralichthys
      olivaceus.
AB  - An understanding of digestibility in marine fish larvae is required to formulate
      a diet to replace zooplankton. Using flounder, this study was aimed at
      determining which digestive enzymes are synthesized in the larval pancreas, and
      how the proteins are cleaved in the digestive canal. Whole mount in situ
      hybridization indicated that the mRNA of all digestive enzyme precursors
      examined, including trypsin, chymotrypsin, elastase, carboxypeptidase A and B,
      and lipase, was expressed in the pancreas of first feeding larvae at 3 days post
      fertilization. In the larvae before differentiation of the stomach, protein
      digestion in the digestive canal mainly depends on pancreatic proteases. So, to
      evaluate protein digestibility in the larval digestive canal, the digestion of
      proteins by pancreatic extract was monitored by gel electrophoresis. It was
      indicated that thyroglobulin, albumin and lactate dehydrogenase were rapidly
      cleaved to polypeptide fragments, but ferritin and catalase exerted resistance to
      proteolysis, suggesting that digestibility in the larval digestive canal differs
      depending on protein species.

PMID- 12044773
TI  - Epithelial cells isolated from chicken jejunum: an experimental model for the
      study of the functional properties of amino acid transport system b(0,+).
AB  - The transport of lysine has been investigated in epithelial cells isolated from
      chicken jejunum. The kinetics of lysine transport and the pattern of interaction
      with zwitterionic amino acids were consistent with system b(0,+) activity, the
      broad-spectrum and Na(+)-independent amino acid transporter. The half-saturation
      constant for lysine entry (K(m)+/-S.E.) was 0.029+/-0.002 mM and the flux was not
      affected significantly by Na(+) replacement with choline. Lysine influx was
      inhibited by L-leucine both in Na(+) and choline medium with inhibition constants
      (K(i)+/-S.E.) 0.068+/-0.006 mM (in Na(+)) and 0.065+/-0.009 mM (in choline).
      Other inhibitory amino acids (K(i)+/-S.E.) were (mM): L-tyrosine (0.073+/-0.018),
      L-methionine (0.15+/-0.015), L-cystine (0.42+/-0.04), L-cysteine (1.1+/-0.07), L
      isoleucine (1.1+/-0.09), L-glutamine (1.8+/-0.16) and L-valine (2.5+/-0.13).
      Lysine exit was trans-accelerated (approx. 20 fold) by 2 mM L-lysine and L
      leucine. The flux was resistant to pretreatment of the cells with p
      chloromercuriphenylsulfonate (0.2 mM), which is an inhibitor of system y(+)L, the
      broad-spectrum and cation-modulated transporter.

PMID- 12044774
TI  - Skin morphology and humoral non-specific defence parameters of mucus and plasma
      in rainbow trout, coho and Atlantic salmon.
AB  - Susceptibility to different diseases among related species, such as coho salmon
      (Oncorhynchus kisutch), rainbow trout (Oncorhyncus mykiss) and Atlantic salmon
      (Salmo salar), is variable. The prominence of these species in aquaculture
      warrants investigation into sources of this variability to assist future disease
      management. To develop a better understanding of the basis for species
      variability, several important non-specific humoral parameters were examined in
      juvenile fish of these three economically important species. Mucous protease,
      alkaline phosphatase and lysozyme, as well as plasma lysozyme activities and
      histological parameters (epidermal thickness and mucous cell density, and size)
      were characterized and compared for three salmonids: rainbow trout, Atlantic
      salmon and coho salmon. Rainbow trout had a thicker epidermis and significantly
      more mucous cells per cross-sectional area than the other two species. Rainbow
      trout also had significantly higher mucous protease activity than Atlantic salmon
      and significantly higher lysozyme (plasma and mucus) activities than coho and
      Atlantic salmon, in seawater. Atlantic salmon, on the other hand, had the lowest
      activities of mucous lysozyme and proteases, the thinnest epidermal layer and the
      sparsest distribution of mucous cells, compared with the two other salmonids in
      seawater. Only coho salmon had sacciform cells. Atlantic and coho salmon had
      higher mucous lysozyme activities in freshwater as compared to seawater. There
      was no significant difference between mucous lysozyme activities in any of the
      three species reared in freshwater; however, rainbow trout still had a
      significantly higher plasma lysozyme activity compared with the other two
      species. All three species exhibited significantly lower mucous alkaline
      phosphatase and protease activities in freshwater than in seawater. Our results
      demonstrate that there are significant histological and biochemical differences
      between the skin and mucus of these three salmonid species, which may change as a
      result of differing environments. Variation in these innate immune factors is
      likely to have differing influences on each species response to disease
      processes.

PMID- 12044776
TI  - Protein kinase C and AKT/protein kinase B in CD4+ T-lymphocytes: new partners in
      TCR/CD28 signal integration.
AB  - T-cell biological responses appear to involve the complex interaction of T-cell
      surface receptors, intracellular signaling molecules and the cytoskeleton. Both
      the serine/threonine protein kinase families protein kinase C (PKC) and protein
      kinase B or RAC-PK (AKT/PKB) have been implicated in signal transmission leading
      to activation, differentiation as well as cellular survival of T-lymphocytes. The
      PKC gene family consists of nine diverse isotypes (PKC alpha, beta, gamma, delta,
      epsilon, xi, eta, theta; and iota), the AKT/PKB gene family includes three
      kinases (AKT1/PKB alpha, AKT2/PKB beta, AKT3/PKB gamma). Here, we attempt to
      summarize the regulation as well as downstream signaling pathways of PKC and
      AKT/PKB isotypes, that may act additive in TCR/CD28 induced proliferation and
      survival of peripheral CD4+ T-lymphocytes.

PMID- 12044777
TI  - Binding of polymeric IgG to fibronectin in extracellular matrices: an in vitro
      paradigm for immune-complex deposition.
AB  - We have previously shown a biochemical interaction between fibronectin (Fn) and
      polymeric immunoglobulins (Igs), that we localized to the fourth and fifth N
      terminal type I repeats (4F1.5F1) in Fn and the Fc portion of IgG. Therefore, we
      hypothesized that Fn, as a constituent of the extracellular matrix (ECM) may
      directly bind circulating immune complexes (ICs) causing their deposition,
      thereby contributing to the pathogenesis of IC diseases. As an in vitro paradigm
      to test this idea, we have generated Fn-containing ECMs from varied cells in
      culture and demonstrated a saturable dose-dependent binding of aggregated (agg)
      IgG, as a prototype of ICs, as well as the binding of both heat and cold
      aggregated purified type I cryoglobulins (CGs) to these ECMs. No binding was
      observed to ECMs (Matrigel) that do not contain Fn. Characteristic of our
      previous findings, polymeric but not monomeric IgG bound to the acellular Fn
      containing ECMs. To further demonstrate the specificity of the interaction and
      implicate matrix Fn in the binding of aggIgG, complete inhibition of binding of
      aggIgG to Fn was achieved by blocking Fn on the ECMs with anti-Fn antiserum and
      by preincubation of the Ig aggregates with anti-human IgG antibodies. By
      competing the binding interaction with fluid phase Fn and the Ig-binding site on
      Fn, 4F(1).5F(1), 70% inhibition was obtained. Additional experiments performed
      with purified CGs show that an identical dose-dependent increase in Fn binding
      occurred using both preformed and forming cryoprecipitates suggesting that Fn
      does not confer cryoprecipitation of CGs and that the specific association of Fn
      with cryoprecipitates probably results from their polymeric configuration. Our
      results support the notion that Fn, as it exits in expanding ECMs characteristic
      of glomerulonephropathies and rheumatoid synovial disease, specifically interacts
      with complexed/polymeric Igs, thereby perpetuating IC deposition and playing a
      role in the pathogenesis of IC diseases.

PMID- 12044778
TI  - The kappa gene repertoire of human neonatal B cells.
AB  - The kappa chain repertoire of individual IgD(+) human neonatal B cells was
      analyzed using a single cell PCR technique. A total of 104 productive and 90 non
      productive VkappaJkappa rearrangements from three cord blood B cell samples were
      sequenced and compared to the adult IgM(+) peripheral B cell VkappaJkappa
      repertoire. All six Vkappa families were present in neonatal B cells, but the
      distribution was not random. In the non-productive repertoire Vkappa2 and Vkappa6
      families were less frequent, Vkappa1 and Vkappa3 families were as frequent, and
      Vkappa4 and Vkappa5 families were more frequent than expected from random chance.
      Notably, the Vkappa2 family was negatively selected into the productive
      repertoire. In contrast, the Vkappa1 family was positively selected because of
      positive selection of three specific genes, O12/O2, L12a and L9. B3 (Vkappa4) and
      B2 (Vkappa5) were over-represented in the non-productive repertoire and then were
      expressed less frequently in the productive repertoire. In contrast, the Vkappa3
      family gene, A27, was also over-represented in the non-productive repertoire but
      not further selected into the productive repertoire. Compared to the adult
      repertoire, junctional diversity was less marked because of a diminished
      influence of TdT activity, whereas the mean CDR3 length was comparable to that of
      normal adult B cells. Comparison of the distribution of Vkappa and Jkappa genes
      with those found in normal adult subjects suggested that there was less receptor
      editing in neonatal B cells. When neonatal CD5(+) B cells were compared with CD5(
      ) IgD(+) B cells, it was noted that the Vkappa gene A30 was used only in CD5(+) B
      cells in both the productive and non-productive repertoires. The results indicate
      that the usage of Vkappa genes by neonatal B cells is biased by both intrinsic
      molecular processes and selection. The evidence of selection indicates that the
      Vkappa repertoire is shaped by self antigens, since exposure to exogenous
      antigens is limited at the time of birth.

PMID- 12044779
TI  - Myb proteins repress human Ig epsilon germline transcription by inhibiting STAT6
      dependent promoter activation.
AB  - Cytokine-dependent induction of correctly spliced germline (GL) transcripts is
      required to target the appropriate switch region for class switch recombination.
      GL transcription is linked to the cell cycle and the number of cell divisions
      through mechanisms that have not been defined. The human proximal epsilon GL
      promoter contains an IL-4 responsive element (IL-4RE) that binds STAT6 and is
      sufficient to confer IL-4 inducibility to a heterologous promoter in transient
      transfection studies. We show herein that the IL-4RE contains a novel Myb binding
      motif that overlaps the 3' end of the STAT6 palindrome. EMSA analysis showed
      binding to the IL-4RE of endogenous Myb proteins expressed in BL-2 B cells and
      Jurkat T cells. However, double occupancy of a probe spanning both STAT6 and Myb
      binding motifs could not be detected. Thus, binding of either factor may prevent
      protein/DNA interactions at the other site, raising the possibility that Myb
      binding may interfere with STAT6-dependent activation of the IL-4RE. Indeed,
      cotransfection of A-Myb or c-Myb expression vectors in HEK293 and BL-2 cells
      suppressed STAT6-dependent transcription from a reporter construct containing
      four copies of the IL-4RE cloned upstream of a minimal thymidine kinase promoter.
      Most importantly, overexpression of A-Myb was sufficient to suppress IL-4-induced
      endogenous epsilon GL transcription in BL-2 cells. Our results indicate that Myb
      proteins, which are known to act as cell cycle sensors, may play an important
      mechanistic role in the in vivo regulation of epsilon GL transcription in human B
      cells.

PMID- 12044780
TI  - Analysis of two acidic P6 pocket residues in the pH dependency of peptide binding
      by I-E(k).
AB  - Peptide binding to major histocompatibility complex (MHC) class II molecules is
      optimal at mildly acidic pH. X-ray crystal structures solved for the murine class
      II molecule I-E(k) revealed an interesting localization of negatively charged
      residues within the P6 pocket, which may have implications in the pH dependency
      of peptide binding. Protonation of these critical residues, under acidic
      conditions, has been proposed to be important for the formation of stable class
      II-peptide complexes. In this study, we address a possible role for these charged
      residues in the pH dependency of peptide binding. An I-E(k) mutant was generated
      in which two acidic residues of the P6 pocket were substituted with uncharged
      residues. This class II mutant was expressed, purified, and tested for its
      ability to bind peptides. The mutant I-E(k) was observed to load peptides
      optimally at mildly acidic pH. Peptide binding to the mutant was enhanced in the
      presence of DM, and optimal DM-enhanced binding occurred in the acidic pH range.
      These findings indicate that structural changes other than protonation of acidic
      residues in pocket 6 must play a dominant role in pH-regulated peptide binding to
      I-E(k).

PMID- 12044782
TI  - DNA methylation dominates transcriptional silencing of Pax5 in terminally
      differentiated B cell lines.
AB  - Pax5 plays a key role in the progression of B cell development. Its expression is
      observed in a wide range of cell types from early lineage-committed precursors up
      to mature B cells, but is silenced in terminal differentiated plasma cells. In
      this report, we show that DNA methylation is involved in the silencing of Pax5.
      In the Pax5-expressing cell lines 38B9 (pre-B) and 2PK-3 (mature B), all CpG
      sites in TATA-containing upstream promoter were unmethylated, whereas these sites
      were completely methylated in myeloma cell lines FO and Sp-2/0, which do not
      express Pax5. Demethylation of FO and Sp-2/0 with 5-aza-2'-deoxycytidine (5-aza
      dC) resulted in Pax5 re-expression with the concomitant expression of CD19 and mb
      1 genes, which are known to be the target genes of Pax5. Re-expression of Pax5
      was also induced by trichostatin A (TSA), which was a specific inhibitor of
      histone deacetylase. This re-expression was, however, transcribed only from the
      TATA-less downstream promoter. Taken together, we concluded that the upstream
      promoter was predominantly inactivated by DNA methylation, while the downstream
      promoter was repressed by the histone deacetylation. This synergetic inactivation
      of two promoters results in the final silencing of Pax5 expression in terminally
      differentiated B cell lines.

PMID- 12044781
TI  - Combinatorial regulation of the murine RAG-2 promoter by Sp1 and distinct
      lymphocyte-specific transcription factors.
AB  - The recombination activation genes, RAG-1 and RAG-2, encode the critical
      components of the recombinase complex responsible for the generation of
      functional antigen receptor genes. In order to gain an insight into the
      transcription factors and cis-acting elements that regulate the lymphocyte
      specific expression of RAG-2, the promoter-region of this gene was isolated and
      characterized. This analysis demonstrated that a relatively small promoter
      fragment could confer lymphocyte-restricted expression to a reporter construct.
      Our work and that of others subsequently revealed that RAG-2 promoter expression
      is positively regulated by BSAP (PAX-5) and c-Myb transcription factors in B- and
      T-lineage cells, respectively. Although BSAP and c-Myb were deemed necessary for
      lymphocyte-specific expression, our analysis also uncovered a G-rich region at
      the 5'-end of the core promoter that was essential for full activity in
      lymphocyte cell lines. Site-directed mutagenesis revealed that a GA-box within
      the G-rich region was required for full promoter activity and subsequent DNA
      binding assays demonstrated that this element was specifically recognized by Sp1.
      Apart from showing that Sp1 interacts within the RAG-2 promoter, we also
      demonstrate that the Sp1-binding site is necessary for the high-level activation
      of this promoter.

PMID- 12044784
TI  - Inhibitory effect of acetylsalicylic acid on metalloproteinase activity in human
      lung adenocarcinoma at different stages of differentiation.
AB  - The mechanism underlying the anticancer effect of nonsteroidal anti-inflammatory
      drugs (NSAIDs) is not clear. We addressed the question whether the alterations in
      collagen content in lung adenocarcinomas reported in previous studies result from
      dysregulation of gelatinolytic activity and whether the activity is altered by
      acetylsalicylic acid in vitro. Human lung adenocarcinomas were divided into three
      groups: well-differentiated (G1), moderately differentiated (G2) and poorly
      differentiated (G3) tumors. Each group was compared with normal lung tissue with
      respect to tissue collagen and collagen degradation product content
      (hydroxyproline assay), gelatinolytic activity (zymography) and the expression of
      matrix metalloproteinases, MMP-2 and MMP-9 (Western immunoblot). Moreover, in the
      studied tissues, the effect of acetylsalicylic acid on gelatinolytic activity was
      measured. The lung adenocarcinoma G1 had a similar collagen content as normal
      lung tissue but increased amounts of collagen degradation products and free
      hydroxyproline. These phenomena were accompanied by a marked increase in
      gelatinolytic activity (MMP-2 and MMP-9) in the G1 tumor. In adenocarcinoma G2,
      the free hydroxyproline content and gelatinolytic activity were increased, while
      the collagen and collagen degradation product contents were not markedly altered,
      compared to control. In contrast, adenocarcinoma G3 had an increased tissue
      collagen content (by about 60%), decreased percentage of collagen degradation
      products and similar gelatinolytic activity, compared to normal lung.
      Acetylsalicylic acid was found to inhibit gelatinolytic activity both in control
      and adenocarcinoma tissues, preferentially the active forms of gelatinases MMP-2
      and MMP-9. The results suggest that human lung adenocarcinoma G1, through an
      elevated expression of the activated forms of both MMP-2 and MMP-9, may represent
      a more invasive phenotype than less differentiated tumors G2 or G3. It indicates
      that lung adenocarcinoma G1 should be considered as a possible target for
      metalloproteinase inhibitory therapy. Acetylsalicylic acid may be such a
      therapeutical agent in cancer prevention or early stages of tumor growth.

PMID- 12044785
TI  - Effects of [(pF)Phe(4)]nociceptin/orphanin FQ-(1-13)NH(2) on GTPgamma(35)S
      binding and cAMP formation in Chinese hamster ovary cells expressing the human
      nociceptin/orphanin FQ receptor.
AB  - Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the N/OFQ receptor
      (NOP). In this study using Chinese hamster ovary (CHO) cells expressing the human
      NOP (CHO(hNOP)) and GTPgamma(35)S binding and cAMP inhibition assays, we have
      characterised a novel N/OFQ ligand, [(pF)Phe(4)]N/OFQ-(1-13)NH(2),
      ([(pF)Phe(4)]). [(pF)Phe(4)] was produced by insertion of a fluorine atom into
      the para position of the phenyl ring of Phe(4) of the truncated N/OFQ peptide
      N/OFQ-(1-13)NH(2). In CHO(hNOP) membranes [(pF)Phe(4)] and N/OFQ-(1-13)NH(2)
      stimulated GTPgamma35S binding with pEC(50) (mean+/-S.E.M.) values of 9.55+/-0.01
      and 8.94+/-0.5 (P<0.05), respectively. In whole CHO(hNOP) cells [(pF)Phe(4)] and
      N/OFQ-(1-13)NH(2) inhibited forskolin stimulated cAMP formation with pEC(50)
      values of 10.19+/-0.06 and 9.60+/-0.04, respectively (P<0.05). [(pF)Phe(4)] was
      more potent ( approximately 4 fold) than N/OFQ-(1-13)NH(2). In both assays, the
      effects of [(pF)Phe(4)] and N/OFQ-(1-13)NH(2) were pertussis toxin sensitive and
      reversed by the NOP antagonists J-113397 (pA(2)/pK(B) values 7.89-8.53) and III
      BTD (pA(2)/pK(B) values 7.27-7.96). [(pF)Phe(4)] is therefore a potent full
      agonist at NOP receptors that will be useful as pharmacological tool for defining
      the role of N/OFQ-NOP system in health and disease.

PMID- 12044786
TI  - Up-regulation of Ca(2+) channels in vas deferens after chronic treatment of
      newborn rats with nifedipine.
AB  - Radioligand binding and contraction techniques were used to verify if L-type
      Ca(2+) channels are modified in rat vas deferens after treatment with the blocker
      nifedipine (15 microg), injected at 7, 14, 21 and 28 days after birth. Vas
      deferens tissue was used 10, 30 and 90 days after the last injection, to verify
      if modifications are persistent. Binding studies with cell membranes, using
      [(3)H]isradipine, showed an increase of the density (B(max)) of Ca(2+) channels
      by more than 60%, after 10 and 30 days, without changes of affinity (K(d)).
      Maximal contractions (E(max)) of KCl, were increased by 106% and 37%,
      respectively, after 10 and 30 days, without changes of apparent affinity (pD(2)).
      After 90 days, the values of B(max), K(d), E(max) and pD(2) were not different
      from the controls. Differences were also not found for rats injected when adult.
      It is concluded that treatment of newborn, but not of adult, rats with nifedipine
      produced a long-lasting, though reversible, up-regulation of L-type Ca(2+)
      channels.

PMID- 12044788
TI  - Novel action of lignans isolated from Hernandia nymphaeifolia on Ca(2+) signaling
      in renal tubular cells.
AB  - The effect of five lignans, epi-aschantin, epi-magnolin, epi-yangambin,
      deoxypodophyllotoxin and yatein, isolated from Hernandia nymphaeifolia on Ca(2+)
      signaling in Madin-Darby canine kidney cells was examined using fura-2 as a
      Ca(2+) indicator. These lignans at concentrations between 10 and 100 microM
      increased [Ca(2+)](i) in a concentration-dependent manner. Removal of
      extracellular Ca(2+) abolished the Ca(2+) signals evoked by 50 microM of the
      lignans. La(3+)(50 microM) abolished the Ca(2+) signals induced by 100 microM of
      epi-aschantin, epi-magnolin and epi-yangambin, and 20 microM
      deoxypodophyllotoxin, but inhibited by 60% 50 microM yatein-induced responses.
      All five lignans (50-100 microM) inhibited by 42-65% thapsigargin-induced
      capacitative Ca(2+) entry, and inhibited by 23-61% thapsigargin-induced
      intracellular Ca(2+) release. Epi-yangambin (100 microM), epi-magnolin (100
      microM), and epi-aschantin (100 microM) inhibited by 8-38% 10 microM ATP-induced
      Ca(2+) release. Trypan blue exclusion revealed that incubation with
      deoxypodophyllotoxin or yatein (but not the other lignans) decreased cell
      viability in a concentration-dependent manner. Together, the results suggest
      that, in renal tubular cells, these lignans exert multiple actions on Ca(2+)
      signaling. They caused Ca(2+) influx but reduced thapsigargin-induced
      capacitative Ca(2+) entry and also thapsigargin- and ATP-induced Ca(2+) release.
      Additionally, deoxypodophyllotoxin and yatein may be cytotoxic.

PMID- 12044787
TI  - Ca(2+) channel properties in smooth muscle cells of the urinary bladder from pig
      and human.
AB  - Ca(2+) channel properties of pig and human bladder smooth muscle were
      investigated utilizing standard whole-cell patch clamp techniques. Both the
      amplitude obtained and the current density of Ca(2+) channel current evoked by
      step depolarization were larger in human than in pig myocytes. The inward
      currents were sensitive to an L-type Ca(2+) channel antagonist, nifedipine, the
      effects of which were not significantly different between species. In both
      species, prior application of ATP (0.1 mM) had no effect on activation of this
      voltage-sensitive channel current, while a muscarinic receptor agonist, carbachol
      (0.1 mM), significantly attenuated the amplitude of this current. Furthermore,
      inclusion of GDP-beta-S or Heparin in the pipette abolished or had no effect on
      the suppression of Ca(2+) current by carbachol, respectively. These results
      forward the pig as a good model for the human in detrusor Ca(2+) channel
      properties, especially with regard to neural modulation, although voltage
      sensitive Ca(2+) channels seem to make greater contribution in human bladder
      physiology.

PMID- 12044789
TI  - 2-Chloro-N(6)-cyclopentyladenosine, adenosine A(1) receptor agonist, antagonizes
      the adenosine A(3) receptor.
AB  - The potent adenosine A(1) receptor agonists, N(6)-cyclopentyladenosine (CPA) and
      2-chloro-N(6)-cyclopentyladenosine (CCPA), were studied in Chinese hamster ovary
      (CHO) cells expressing the human adenosine A(3) receptor. CPA, but not CCPA,
      induced phosphoinositide turnover. CPA inhibited forskolin-stimulated cyclic AMP
      production (EC(50) value of 242+/-47 nM). CCPA competitively antagonized the
      effects of agonist Cl-IB-MECA (2-chloro-N(6)-(3-iodobenzyl)-5'-N
      methylcarbamoyladenosine) with K(B) value of 5.0 nM. CPA competition curves
      versus the A(3) antagonist radioligand [3H]PSB-11 (8-ethyl-4-methyl-2-phenyl-(8R)
      4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one) were right-shifted four-fold by
      100 microM GTP, which had no effect on binding of CCPA or the antagonist MRS 1220
      (N-[9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-yl]benzene
      acetamide). Thus, CCPA is a moderately potent antagonist (K(i)=38 nM) of the
      human A(3) adenosine receptor.

PMID- 12044790
TI  - Cannabinoid receptor antagonism and inverse agonism in response to SR141716A on
      cAMP production in human and rat brain.
AB  - The effects of cannabinoid drugs on cAMP production were examined in mammalian
      brain. The cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4
      morpholinyl)methyl]pyrrolo[1,2,3,-d,e-1,4-benzoxazin-6-yl]-(1-naphthalenyl)
      methanone (WIN55,212-2) decreased forskolin-induced cAMP accumulation in a
      concentration-dependent manner (10(-8)-10(-5) M) in membranes from several rat
      and human brain regions, this effect being antagonized by 10(-5) M N-(piperidin-1
      yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      (SR141716A). Furthermore, high micromolar concentrations of SR141716A evoked a
      dose-dependent increase in basal cAMP in rat cerebellum and cortex, as well as in
      human frontal cortex. This effect was antagonized by WIN55,212-2 and abolished by
      N-ethylmaleimide, consistent with the involvement of cannabinoid CB(1) receptors
      through the activation of G(i/o) proteins. These results suggest a ligand
      independent activity for cannabinoid CB(1) receptor signaling cascade in
      mammalian brain.

PMID- 12044791
TI  - Cyclosporin A inhibits angiotensin II-induced c-Jun NH(2)-terminal kinase
      activation but not protein synthesis in vascular smooth muscle cells.
AB  - Angiotensin II activates three major mitogen-activated protein kinases (MAPK) in
      vascular smooth muscle cells. Although other angiotensin II-induced MAPKs
      activation require transactivation of a growth factor receptor, the detailed
      mechanism by which angiotensin II activates c-Jun NH(2)-terminal kinase (JNK)
      remains unclear. Here, an immunosuppressant, cyclosporin A but not FK506,
      selectively inhibited angiotensin II-induced JNK activation in vascular smooth
      muscle cells. However, cyclosporin A had no inhibitory effect on angiotensin II
      induced protein synthesis. Thus, angiotensin II-induced JNK activation but not
      protein synthesis is mediated by a mechanism sensitive to cyclosporin A, which is
      independent from calcineurin in vascular smooth muscle cells.

PMID- 12044792
TI  - Imipramine but not 5-HT(1A) receptor agonists or neuroleptics induces adaptive
      changes in hippocampal 5-HT(1A) and 5-HT(4) receptors.
AB  - It has been reported that the treatment with a tricyclic antidepressant
      imipramine induces an increase in the sensitivity of 5-HT(1A) receptors and a
      decrease in the sensitivity of 5-HT(4) receptors in the rat hippocampus. 5-HT(1A)
      receptor agonists and neuroleptics also affect 5-HT(1A) receptors in different
      brain areas; therefore, it was of interest to compare their effects on
      hippocampal 5-HT receptors with the influence of the well-established
      antidepressant imipramine. We studied the effects of repeated treatment with
      imipramine, the 5-HT(1A) receptor agonists 8-hydroxy-2(di-n-propylamino)tetralin
      (8-OH-DPAT) and buspirone, and the neuroleptics haloperidol and clozapine on the
      sensitivity of rat hippocampal CA1 neurons to 5-HT(1A)- and 5-HT(4) receptor
      activation. Imipramine was administered for 21 days (10 mg/kg p.o., twice daily),
      8-OH-DPAT for 7 days (1 mg/kg s.c., twice daily) and buspirone for 21 days (5
      mg/kg s.c., twice daily). The rats received haloperidol (1 mg/kg) and clozapine
      (30 mg/kg) for 6 weeks in drinking water. Hippocampal slices were prepared 2 days
      after the last treatment with imipramine, 8-OH-DPAT or buspirone, and 5 days
      after the last treatment with the neuroleptics. Using an extracellular in vitro
      recording, we studied changes in the amplitude of stimulation-evoked population
      spikes, induced by 5-HT, 8-OH-DPAT and the 5-HT(4) receptor agonist zacopride.
      Activation of 5-HT(1A) receptors decreased, while activation of 5-HT(4) receptors
      increased the amplitude of population spikes. Imipramine significantly enhanced
      the inhibitory effects of 5-HT and 8-OH-DPAT, and attenuated the excitatory
      effect of zacopride. No other treatment used in the present study changed the
      sensitivity of hippocampal CA1 neurons to 5-HT(1A) and 5-HT(4) receptors
      activation. These findings indicate that adaptive changes in the sensitivity of
      hippocampal neurons to 5-HT(1A) and 5-HT(4) receptors agonists are specific to
      imipramine and may thus-at least partly-mediate its effects.

PMID- 12044793
TI  - Effects of striatal injections of GABA(A) receptor agonists and antagonists in a
      genetic animal model of paroxysmal dystonia.
AB  - The underlying mechanisms of idiopathic dystonias are poorly understood. The
      dystonic phenotype in the dt(sz) mutant hamster, a model of paroxysmal dystonia,
      has been suggested to be based on a deficit of gamma-aminobutyric acid
      (GABA)ergic interneurons and changes of the GABA(A)-benzodiazepine receptor
      complex in the striatum. In order to confirm and extend previous observations,
      the effects of compounds which bind to different sites of the GABA(A) receptor on
      the severity of dystonia were determined after striatal microinjections in
      comparison to systemic treatments in dt(sz) mutants. The GABA(A) receptor agonist
      (muscimol) and the benzodiazepine (flurazepam) reduced the severity of dystonia
      after striatal and systemic injections. The antidystonic effects of the
      barbiturate phenobarbital were less marked both after striatal and
      intraperitoneal administration of drugs. Intrastriatal injections of GABA delayed
      the onset of dystonic attacks. Striatal and systemic treatments with the GABA(A)
      receptor antagonist, bicuculline, and with pentylenetetrazole, which reduces
      GABAergic function, accelerated the onset of dystonia at subconvulsant doses. The
      benzodiazepine receptor antagonists flumazenil aggravated dystonia after systemic
      and intrastriatal injections. In all, the present data substantiate the relevance
      of striatal GABAergic disinhibition in the pathogenesis of paroxysmal dystonia in
      dt(sz) mutants.

PMID- 12044794
TI  - Paracetamol exerts a spinal, tropisetron-reversible, antinociceptive effect in an
      inflammatory pain model in rats.
AB  - Experiments were performed in carrageenin-treated rats to study, the
      antinociceptive and anti-inflammatory effects of paracetamol intravenously (i.v.)
      or intrathecally (i.t.) injected on rats submitted to a mechanical noxious
      stimulus. The influence of intrathecal tropisetron, a 5 hydroxytryptamine(3) (5
      HT(3)) receptor antagonist, on the antinociceptive effects of paracetamol, was
      also studied. Paracetamol induced a significant antinociceptive effect after
      (100, 200 and 300 mg/kg) i.v. and (50, 100 and 200 microg/rat) i.t. injection,
      but no change occurred on edema volume. The effect of paracetamol was totally
      inhibited by tropisetron (10 microg/rat, i.t.). The foregoing results demonstrate
      that, in conditions of inflammatory pain, paracetamol exerts a central
      antinociceptive effect involving spinal 5-HT(3) receptors, without inducing any
      anti-inflammatory action. These data, give further arguments to consider
      paracetamol as a central analgesic drug which must be distinguished from non
      steroidal anti-inflammatory drugs (NSAIDs), which justifies the usual combination
      of paracetamol in post-operative pain.

PMID- 12044795
TI  - Effect of low-affinity NMDA receptor antagonists on electrical activity in mouse
      cortical slices.
AB  - The objective of this study was to investigate the effects of three low-affinity
      NMDA receptor antagonists, MRZ 2/279 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane
      HCl), AR-R 15896AR ([+]-alpha-phenyl-2-pyridine-ethanamine diHCl) and
      dextromethorphan on epileptiform activity in vitro. Epileptiform discharges were
      elicited in DBA/2 mouse cortical slices by perfusion with Mg(2+)-free artificial
      cerebrospinal fluid. MRZ 2/279, AR-R 15896AR and dextromethorphan all reversibly
      decreased the frequency of the discharges in a concentration-dependent manner.
      The IC(50)'s for MRZ 2/279, AR-R 15896AR and dextromethorphan were 5.2, 10.8 and
      55.9 microM, respectively. These low-affinity NMDA receptor antagonists may be
      proved to be clinically effective with fewer adverse effects than drugs with high
      affinity for the NMDA receptor-operated channel.

PMID- 12044797
TI  - Blockade by the cannabinoid CB(1) receptor antagonist, SR 141716, of alcohol
      deprivation effect in alcohol-preferring rats.
AB  - The present study investigated the effect of the cannabinoid CB(1) receptor
      antagonist, SR 141716 (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-3-pyrazole-carboxamide), on alcohol deprivation effect (i.e. the temporary
      increase in alcohol intake after a period of alcohol withdrawal) in Sardinian
      alcohol-preferring (sP) rats. As expected, alcohol-deprived rats virtually
      doubled voluntary alcohol intake during the first hour of re-access. Acute
      administration of SR 141716 (0, 0.3, 1 and 3 mg/kg, i.p.) completely abolished
      the alcohol deprivation effect. These results suggest that the cannabinoid CB(1)
      receptor is part of the neural substrate mediating the alcohol deprivation effect
      and that SR 141716 may possess anti-relapse properties.

PMID- 12044796
TI  - Differential effects of chronic antidepressant treatments on micro- and delta
      opioid receptors in rat brain.
AB  - We performed an autoradiographic study of [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin
      (DAMGO)-sensitive [(3)H]naloxone binding to micro-opioid receptors and of
      [(3)H][D-Pen(2),D-Pen(5)]enkephalin (DPDPE) binding to delta-opioid receptors in
      the rat brain after 4- or 21-day treatments with paroxetine, reboxetine and
      moclobemide to investigate the participation of these receptors in the adaptive
      mechanisms occurring during the delay of action of new generation
      antidepressants. Paroxetine increased micro-opioid receptor binding site density
      in cingulate and insular cortices, dorsal endopiriform nucleus (4 days) and
      olfactory tubercle (21 days) and decreased it in thalamus (21 days). Reboxetine
      increased it in amygdala (4 days), hippocampus and thalamus (21 days) and
      decreased it in dorsal raphe (4 days). Moclobemide increased it in hippocampus (4
      days) and decreased it in anterior olfactory nucleus, frontal cortex, amygdala
      and hypothalamus (21 days). Moclobemide increased delta-opioid receptor binding
      site density in frontal cortex and amygdala (4 days) and decreased it in amygdala
      and colliculi (21 days). Opioid receptors displayed distinct patterns of
      adaptations in response to the three antidepressants studied.

PMID- 12044798
TI  - Improved efficacy of fluoxetine in increasing hippocampal 5-hydroxytryptamine
      outflow in 5-HT(1B) receptor knock-out mice.
AB  - To test for the contribution of the 5-HT(1B) receptor subtype in mediating the
      effects of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), we used
      intracerebral in vivo microdialysis in awake, freely moving 5-HT(1B) receptor
      knock-out mice. We show that a single systemic administration of fluoxetine (1, 5
      or 10 mg/kg, i.p.) increased extracellular serotonin levels [5-HT](ext) in the
      ventral hippocampus and frontal cortex of wild-type and mutant mice. However, in
      the ventral hippocampus, fluoxetine, at the three doses studied, induced a larger
      increase in [5-HT](ext) in knock-out than in wild-type mice. In the frontal
      cortex, the effect of fluoxetine did not differ between the two genotypes. The
      region-dependent response to fluoxetine described here in mutants confirms data
      we recently reported for another SSRI, paroxetine. These data suggest that 5
      HT(1B) autoreceptors limit the effects of selective serotonin reuptake inhibitors
      on dialysate 5-HT levels at serotonergic nerve terminals located mainly in the
      ventral hippocampus. Alternative mechanisms, e.g., changes in 5-HT transporter
      and/or 5-HT(1A) receptor density in 5-HT(1B) receptor knock-out mice could also
      explain these findings.

PMID- 12044799
TI  - Differential neurobehavioral deficits induced by apomorphine and its oxidation
      product, 8-oxo-apomorphine-semiquinone, in rats.
AB  - Apomorphine is a potent dopamine receptor agonist, which has been used in the
      therapy of Parkinson's disease. It has been proposed that apomorphine and other
      dopamine receptor agonists might induce neurotoxicity mediated by their quinone
      and semiquinone oxidation derivatives. The aim of the present study was to
      evaluate the possible neurobehavioral effects of apomorphine and its oxidation
      derivative, 8-oxo-apomorphine-semiquinone (8-OASQ). Adult female Wistar rats were
      treated with a systemic injection of apomorphine (0.05 or 0.5 mg/kg) or 8-OASQ
      (0.05 or 0.5 mg/kg) 20 min before behavioral testing. Apomorphine and 8-OASQ
      induced differential impairing effects on short- and long-term retention of an
      inhibitory avoidance task. Apomorphine, but not 8-OASQ, dose-dependently impaired
      habituation to a novel environment. The memory-impairing effects could not be
      attributed to reduced nociception or other nonspecific behavioral alterations,
      since neither apomorphine nor 8-OASQ affected footshock reactivity or behavior
      during exploration of an open field. The results suggest that oxidation products
      of dopamine or dopamine receptor agonists might induce cognitive deficits.

PMID- 12044800
TI  - Nicotine and bupropion share a similar discriminative stimulus effect.
AB  - Bupropion is a weakly potent central nervous system (CNS) stimulant that is
      marketed both as an antidepressant and as an anti-smoking aid. The mechanism(s)
      by which it produces its effects is not well understood. In the present study,
      the effect of bupropion was examined in rats trained to discriminate the stimulus
      effect of 0.60 mg/kg of (-)-nicotine from saline in a two-lever drug
      discrimination task. In tests of stimulus generalization (substitution), the
      nicotine (ED(50)=0.17 mg/kg) stimulus completely generalized to bupropion
      (ED(50)=5.50 mg/kg). In addition, interaction studies were conducted that
      evaluated the effect of 3.0 mg/kg of bupropion, a dose that when given alone
      produced saline-appropriate responding, in combination with various doses of
      nicotine. This application resulted in an enhancement of the potency of nicotine
      (ED(50)=0.05 mg/kg), as indicated by a leftward shift of the nicotine dose-effect
      function. In tests of stimulus antagonism, various doses of bupropion were
      administered prior to the training dose of nicotine and were found to be
      ineffective as antagonists of the nicotine stimulus. In contrast, the nicotinic
      acetylcholine receptor (nicotine receptor) antagonist mecamylamine (AD(50)=0.40
      mg/kg) completely blocked the stimulus effect of nicotine. Mecamylamine did not
      attenuate the stimulus generalization of bupropion. The results demonstrated that
      bupropion can produce a nicotine-like response in nicotine-trained animals, but
      it does so via a mechanism of action that is unlike that of nicotine. It is
      speculated that bupropion may be somewhat effective as an anti-smoking treatment
      in people who are motivated to quit smoking because low doses of bupropion
      produce a nicotine-like effect(s) that serve as a suitable substitute for
      nicotine.

PMID- 12044801
TI  - Role of nitric oxide synthase inhibitors and NMDA receptor antagonist in nicotine
      induced behavioral sensitization in the rat.
AB  - Repeated injections of nicotine are well known to produce progressively larger
      increases in locomotor activity, an effect defined as behavioral sensitization.
      This study was carried out to investigate the role of nitric oxide (NO) and N
      methyl-D-aspartate (NMDA) receptors in nicotine-induced behavioral sensitization.
      Rats were given repeated injections of nicotine (0.4 mg/kg, s.c., twice daily for
      7 days) followed by one challenge injection on the fourth day after the last
      daily injection. Systemic challenge with nicotine produced a much larger increase
      in locomotor activity in nicotine-pretreated rats. Rats were pretreated with the
      nonselective nitric oxide synthase (NOS) inhibitor, N(G)-nitro-arginine-methyl
      ester (L-NAME; 75 mg/kg, i.p.), the selective constitutive NOS inhibitor, N-nitro
      L-arginine (L-NNA; 15 mg/kg, i.p.), the prototypical selective inducible NOS
      inhibitor, aminoguanidine (100 mg/kg, i.p.) or NMDA receptor antagonist, MK-801
      ((5R,10S)-(+)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine; 0.3
      mg/kg, i.p.), 30 min before injections of nicotine during a 7-day development or
      a 3-day withdrawal phase after which challenged with nicotine on day 11.
      Pretreatment with L-NAME, L-NNA and MK-801, but not aminoguanidine, blocked the
      development of nicotine-induced sensitization to subsequent nicotine challenge.
      Injections of MK-801 twice daily during 3-day withdrawal periods after a 7-day
      induction period of nicotine attenuated nicotine-induced behavioral
      sensitization, whereas injections of L-NAME, L-NNA or aminoguanidine had no
      effects on the expression of sensitization produced by repeated nicotine. This
      study demonstrates that NMDA receptors can play a major role in the expression as
      well as development of nicotine-induced behavioral sensitization, and that NO is
      also involved in the development, but not critically involved in the expression
      of behavioral sensitization to nicotine.

PMID- 12044803
TI  - Evaluation of the effects of anti-thromboxane agents in platelet-vessel wall
      interaction.
AB  - We evaluated the capacity of anti-aggregating agents to influence thromboxane
      A(2) and prostacyclin formation, arachidonic acid-endoperoxide redirection,
      platelet aggregation and vessel tone, in isolated rabbit aorta incubated with
      homologous platelets. Picotamide (N,N'bis(3-pyridinylmethyl)-4-methoxy
      isophthalamide), the only dual thromboxane A(2)-synthase inhibitor/receptor
      antagonist in clinical use, inhibited arachidonic acid-induced platelet
      aggregation with low potency, increased 180-fold by aorta presence. It inhibited
      thromboxane A(2) formation in platelets and, in aorta presence, increased
      prostacyclin formation. Ozagrel (OKY-046, (E)-3-(4-(1-imidazolylmethyl)phenyl)-2
      propenoic acid), a pure thromboxane A(2)-synthase inhibitor, behaved similarly to
      picotamide, although the aorta caused a higher (600-fold) shift. The potency of
      the antagonist SQ 29,548 (1S-(1 alpha,2 beta(5Z),3 beta,4 alpha))-7-(3((2
      ((phenylamino)carbonyl)hydrazino)methyl)-7-oxabicyclo(2.2.1)hept-2-yl)-5
      heptenoic acid) was unaffected by aorta. In coincubation experiments, arachidonic
      acid-challenge increased thromboxane A(2)-dependent vessel tone; picotamide
      increased prostacyclin and reduced thromboxane A(2) formation and
      vasoconstriction. Ozagrel mimicked picotamide; aspirin (acetylsalicylic acid)
      reduced aorta contractility, thromboxane A(2) and prostacyclin formation. SQ
      29,548 reduced vasoconstriction without affecting eicosanoids. We demonstrate the
      importance of redirection of eicosanoids in the mechanism of action of
      thromboxane A(2) inhibitors/antagonists within platelet-vascular wall
      interactions. These findings bear relevance in the development of novel anti
      thrombotic drugs.

PMID- 12044802
TI  - Comparison of contractile responses to donitriptan and sumatriptan in the human
      middle meningeal and coronary arteries.
AB  - Donitriptan is a potent, high efficacy agonist at 5-HT(1B/1D) receptors. We
      investigated the contractile effects of donitriptan and sumatriptan on human
      isolated blood vessels of relevance to therapeutic efficacy in migraine (middle
      meningeal artery) and coronary adverse events (coronary artery). Furthermore,
      using the concentration-response curves in the middle meningeal artery, we
      predicted the plasma concentration needed for the therapeutic effect of
      donitriptan. Both donitriptan and sumatriptan contracted the middle meningeal
      artery with similar apparent efficacy (E(max): 103+/-8% and 110+/-12%,
      respectively), but the potency of donitriptan (pEC(50): 9.07+/-0.14) was
      significantly higher than that of sumatriptan (pEC(50): 7.41+/-0.08). In the
      coronary artery, the contraction to donitriptan was biphasic with a significantly
      higher maximal response (E(max): 29+/-6%) than sumatriptan (E(max): 14+/-2%;
      pEC(50): 5.71+/-0.16), yielding two distinct pEC(50) values (8.25+/-0.16 and
      5.60+/-0.24). Incubation with the 5-HT(2) receptor antagonist ketanserin (10
      microM) eliminated the low affinity component of the concentration-response curve
      of donitriptan and the resultant E(max) and pEC(50) were 9+/-2% and 7.33+/-0.21,
      respectively. Ketanserin was without effect on the sumatriptan-induced
      contraction. Based on the middle meningeal artery contraction, concentrations
      (C(max)) of donitriptan that may be expected to have a therapeutic efficacy
      equivalent to that of 50 and 100 mg sumatriptan are predicted to be around 2.5
      and 4.3 nM, respectively. Such concentrations are likely to induce only a small
      coronary artery contraction of 2.9+/-1.5% and 3.8+/-2.0%, respectively; these are
      not different from those by C(max) concentrations of sumatriptan (1.7+/-0.4% or
      2.2+/-0.4%). The present results suggest that, like sumatriptan, donitriptan
      exhibits cranioselectivity and would be effective in aborting migraine attacks
      with a similar coronary side-effect profile as sumatriptan.

PMID- 12044804
TI  - Effect of a humanized monoclonal antibody to von Willebrand factor in a canine
      model of coronary arterial thrombosis.
AB  - The purpose of this study was to investigate the antithrombotic effect and
      bleeding time prolongation of AJW200, a humanized monoclonal antibody to von
      Willebrand factor (vWF), in a canine model of coronary arterial thrombosis.
      AJW200 significantly inhibited cyclic flow reductions, as well as botrocetin
      induced platelet aggregation, at 0.1 mg/kg. A significant prolongation of
      bleeding time was observed at 0.3-1 mg/kg. Approximately 50% occupancy of vWF
      (approximately 0.7 microg/ml AJW200 in plasma) and 80-100% occupancy
      (approximately 20 microg/ml AJW200 in plasma) were needed for the antithrombotic
      effect and the extensive prolongation of bleeding time, respectively. On the
      contrary, the minimal effective dose of abciximab (0.8 mg/kg) was associated with
      a significant prolongation of bleeding time. These results suggest that the
      pharmacological blockade of platelet glycoprotein (GP) Ib-vWF interaction with
      AJW200 results in a safer antithrombotic profile than platelet GPIIb/IIIa
      blockade with abciximab in dogs.

PMID- 12044805
TI  - Affinity profile at alpha(1)- and alpha(2)-adrenoceptor subtypes and in vitro
      cardiovascular actions of (+)-boldine.
AB  - The present study examines the functional and binding affinities of the aporphine
      alkaloid, (+)-boldine, at different alpha(1)- and alpha(2)-adrenoceptor subtypes,
      namely, alpha(1A) (rat vas deferens and kidney) and its L-like state (rabbit
      spleen), alpha(1B) (guinea pig spleen, mouse spleen and rabbit aorta), alpha(1D)
      (rat aorta and pulmonary artery), at possible subtypes of prejunctional alpha(2)
      adrenoceptors in rat and rabbit vas deferens and rat atrium, alpha(2D) in guinea
      pig ileum, cloned human alpha(1)-adrenoceptor subtypes A, B and D and alpha(2)
      adrenoceptor subtypes A, B and C as well as rat alpha(2D)-adrenoceptors.
      Additionally, we investigated its Ca(2+) channel antagonism in vascular and
      cardiac preparations. (+)-Boldine had higher affinity at alpha(1)-adrenoceptor
      subtype A (pA(2)=7.46, pK(i)=7.21) compared with its L-like state (pA(2)=5.63) or
      subtype B (pA(2)=5.98- 6.12, pK(i)=5.79) and subtype D (pA(2)=6.18-6.37,
      pK(i)=6.09). Its affinities at alpha(2)-adrenoceptors in rat and rabbit vas
      deferens and rat atrium (pA(2)=6.02, 6.36, 6.06, respectively) were identical,
      but lower at guinea pig ileum alpha(2D)-adrenoceptors (pA(2)=4.38). (+)-Boldine
      displayed nearly undistinguishable affinity at cloned human alpha(2)-adrenoceptor
      subtypes A, B and C (pK(i)=6.26, 5.79 and 6.35, respectively), whereas its
      affinity at rat alpha(2D)-adrenoceptors was low (pK(i)=4.70). In perfused rat
      kidney, (+)-boldine inhibited K(+)-evoked vasoconstriction at doses 70-fold
      higher than diltiazem. In guinea pig Langendorff heart, (+)-boldine (10(-5) - 2 x
      10(-4) M) was equieffective in increasing coronary flow and in depressing cardiac
      force, while lower concentrations already depressed heart rate. In papillary
      muscles from guinea pig, (+)-boldine (10(-6) - 10(-5) M) mainly prolonged the
      duration of action potential at levels >30% of repolarization. These data reveal
      that (+)-boldine, except for its moderate selectivity (15 to 25-fold) for
      alpha(1A)-adrenoceptors, does not discriminate between the alpha(1)-adrenoceptor
      subtypes B and D and alpha(2)-adrenoceptor subtypes A, B and C, at which the drug
      consistently displays micromolar affinity. In vascular and cardiac preparations,
      (+)-boldine, although being at least 50-fold weaker than diltiazem, shows Ca(2+)
      channel antagonistic properties but no specificity for coronary dilatation
      relative to cardiodepression.

PMID- 12044806
TI  - Hydrogen peroxide-induced intracellular acidosis and electromechanical inhibition
      in the diseased human ventricular myocardium.
AB  - Accumulation of oxygen free radicals is an important mediator of post
      ischemia/reperfusion cardiac dysfunction. However, oxidative injury has not been
      well characterized in human cardiac tissues. In the present study, we superfused
      hydrogen peroxide (H(2)O(2)) into the diseased human ventricle in order to assess
      the effects of oxygen free radicals on the electromechanical parameters and the
      intracellular pH (pH(i)), and to test the ability of certain potential
      cardioprotective agents, including scavengers of hydrogen peroxide
      (dibenzamidostilbene disulfonic acid; DBDS), the.OH free radical (N
      (mercaptopropionyl)-glycine; N-MPG), and the HOCl free radical (L-methionine), to
      protect against oxidative injury. Disease human ventricular tissues were obtained
      from patients undergoing heart transplantation. Electrophysiological experiments
      were performed using a traditional micropipette, while the pH(i) was measured by
      microspectrofluorimetry. We found that (a) H(2)O(2) (30 microM-3 mM) induced a
      significant dose-dependent intracellular acidosis, (b) H(2)O(2) (30 microM-3 mM)
      had a notable dose-dependent biphasic effect on the contractile force (an
      increase, followed by a decrease), while moderate concentrations of H(2)O(2) also
      inhibited the generation of action potential and increased the diastolic resting
      force significantly, and (c) N-MPG caused significant block of both the
      intracellular acidosis and the electromechanical inhibition induced by 3 mM
      H(2)O(2), whereas L-methionine and DBDS did not. Our data suggest that the toxic
      effects of H(2)O(2) are caused mainly through the generation of.OH, which is
      attributed to the intracellular acidosis seen in the diseased human ventricle.

PMID- 12044807
TI  - T-1032, a novel phosphodiesterase type 5 inhibitor, increases the survival of
      cardiomyopathic hamsters.
AB  - To evaluate the influence of T-1032 (methyl2-(4-aminophenyl)-1,2-dihydro-1-oxo-7
      (2-pyridylmethoxy)-4-(3,4,5-trimethoxyphenyl)-3-isoquinoline carboxylate
      sulfate), a potent and relatively selective phosphodiesterase 5 inhibitor, on
      chronic heart failure, we examined the acute hemodynamic profile of T-1032 and
      its chronic effect on the survival of Bio 14.6 cardiomyopathic hamsters. In the
      acute study, T-1032 (1, 10, 100 microg/kg) was administered intravenously by
      means of a dose-escalating procedure in 55-week-old hamsters. T-1032
      significantly reduced both the right and left ventricular end-diastolic pressure
      in a dose-dependent manner. T-1032 modestly reduced the systemic arterial
      pressure at the highest dose (100 microg/kg i.v.). T-1032 did not change the
      heart rate or left ventricular dp/dt(max). In the survival study, chronic
      administration of T-1032 (50 and 500 ppm in a diet) increased survival, and the
      survival rate was 24.2%, 45.4% and 48.5% in the control, 50 and 500 ppm-treated
      groups, respectively. The median survival was 55, 58 and 58 weeks in control, 50
      and 500 ppm-treated groups, respectively. Analysis of the survival curves
      revealed that T-1032 (500 ppm) significantly increased the survival of these
      hamsters (P<0.05 vs. control). It was concluded that T-1032 had beneficial
      hemodynamic effects on heart failure in Bio 14.6 cardiomyopathic hamsters, and
      the favorable hemodynamic changes induced by T-1032 were partly related to the
      increase in the survival of these hamsters. Phosphodiesterase type 5 inhibitors
      may have therapeutic potential for the treatment of chronic heart failure.

PMID- 12044808
TI  - Effect of mitragynine, derived from Thai folk medicine, on gastric acid secretion
      through opioid receptor in anesthetized rats.
AB  - Mitragynine, an indole alkaloid from Thai folk medicine Mitragyna speciosa,
      exerts agonistic effects on opioid receptors. Gastric acid secretion is proposed
      to be regulated by opioid receptors in the central nervous system (CNS).
      Previously, we reported the dual roles (inhibition via micro-opioid receptors and
      stimulation via kappa-opioid receptors) of the opioid system in the central
      control of gastric acid secretion. We investigated whether mitragynine affects
      gastric acid secretion via opioid receptors in the CNS. Injection of mitragynine
      (30 microg) alone into the lateral cerebroventricle did not have a significant
      effect on basal gastric acid secretion in the perfused stomach of anesthetized
      rats. Injection of mitragynine (3-30 microg) into the fourth cerebroventricle,
      like morphine, inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion. The
      inhibitory effect of mitragynine (30 microg) was reversed by naloxone (100
      microg). These results suggest that mitragynine has a morphine-like action on
      gastric acid secretion in the CNS.

PMID- 12044809
TI  - Piceatannol, a Syk-selective tyrosine kinase inhibitor, attenuated antigen
      challenge of guinea pig airways in vitro.
AB  - Activation of nontransmembrane protein tyrosine kinases, such as Lyn and Syk, has
      been shown to be the earliest detectable signaling response to Fc receptor (Fc
      epsilon RI) cross-linking on mast cells leading to mast cell degranulation. The
      present study examined the effects of piceatannol (3,4,3',5'-tetrahydroxy-trans
      stilbene, 10-100 microM), a Syk-selective tyrosine kinase inhibitor, on ovalbumin
      induced anaphylactic contraction of isolated guinea pig bronchi and release of
      histamine and peptidoleukotrienes from chopped lung preparations. Pretreatment
      with piceatannol slightly suppressed ovalbumin-induced peak anaphylactic
      bronchial contraction but markedly (P<0.05) facilitated relaxation of the
      anaphylactically contracted bronchi. Piceatannol did not inhibit direct histamine
      , leukotriene D(4)- or KCl-induced bronchial contraction, nor revert an existing
      anaphylactic bronchial contraction. Piceatannol, at 30 microM and above,
      significantly (P<0.05) prevented ovalbumin-induced release of both histamine and
      peptidoleukotrienes from lung fragments. Piceatannol did not inhibit exogenous
      arachidonic acid-induced release of peptidoleukotrienes from lung fragments. Our
      data show for the first time that inhibition of Syk tyrosine kinase can attenuate
      anaphylactic bronchial contraction in vitro, probably via inhibition of mast cell
      degranulation.

PMID- 12044810
TI  - Delineation of the protective action of zinc sulfate on ulcerative colitis in
      rats.
AB  - The protective action of zinc compounds in Crohn's disease-like inflammatory
      bowel disease in animals has been shown. A similar action of zinc sulfate on
      ulcerative colitis has not been defined. The present study aimed to delineate the
      protective action of zinc sulfate and the pathogenic mechanisms of 2,4
      dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc
      sulfate at different concentrations was given either orally (p.o.) or rectally
      (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic
      inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally
      to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase
      activities. The involvement of mast cell degranulation and histamine release in
      the pathogenesis of DNBS-induced colitis was determined by using a mast cell
      stabilizer (ketotifen) and histamine receptor blockers (terfenadine and
      ranitidine). DNBS given rectally produced inflammation and ulceration in rats
      with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not
      xanthine oxidase activity was sharply increased by this agent. Intrarectal
      administration of zinc solution and parenteral injection of histamine blockers
      significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase
      activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal
      injury and myeloperoxidase activity in the colon. In conclusion, mast cell
      degranulation followed by histamine release plays an important role in the
      pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a
      therapeutic effect against this colitis model, perhaps through the reduction of
      inflammation and inhibition of the above pathogenic mechanisms.

PMID- 12044811
TI  - Effect of 7-nitroindazole on drug-priming reinstatement of D-methamphetamine
      induced conditioned place preference.
AB  - The study investigated the role of nitric oxide (NO) in the relapse to drug
      seeking behavior induced by D-methamphetamine. After the induction of D
      methamphetamine (1 mg/kg) conditioned place preference, the rewarding effect
      became extinct 6 weeks later. The extinguished place preference was reinstated by
      D-methamphetamine (0.125 mg/kg) injection, an effect which was attenuated by 7
      nitroindazole (12.5 and 25 mg/kg) pretreatment. The results demonstrate that NO
      is involved in relapse primed by D-methamphetamine injection.

PMID- 12044812
TI  - sigma(2) Receptors regulate changes in sphingolipid levels in breast tumor cells.
AB  - sigma(2) Receptors induce apoptosis in various cell types. The sphingolipid,
      ceramide as well as the sphingoid bases are involved in cell proliferation.
      Sphingolipids of MCF-7/Adr- and T47D breast tumor cells were metabolically
      radiolabeled. The sigma(2) receptor agonists (+)-1R,5R-E-8-(3,4
      dichlorobenzylidene)-5-(3-hydroxyphenyl)-2-methylmorphan-7-one (CB-184) and 1S,2R
      (--)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)
      cyclohexylamine (BD737) caused dose-dependent increases in [(3)H]ceramide, with
      concomitant decreases in [(3)H]sphingomyelin. Both effects were attenuated by the
      novel sigma(2) receptor antagonist, N-phenethylpiperidine oxalate (AC927).
      sigma(2) Receptors may produce effects on cell growth and apoptosis by regulating
      the sphingolipid pathway.

PMID- 12044813
TI  - The sensory nitrergic nature of the hepatic insulin sensitizing substance
      mechanism in conscious rabbits.
AB  - Functional deterioration of sensory fibres in the anterior hepatic plexus or
      intraportal administration of 7-nitro indazole (1 mg/kg), a selective inhibitor
      of neural nitric oxide (NO) synthase, caused insulin resistance as determined by
      hyperinsulinaemic (100 micro U/ml) euglycaemic (5.5 mmol/l) glucose clamping in
      chronically instrumented conscious rabbits. Intraportal nitroglycerin restored
      insulin sensitivity in either case. We conclude that NO of sensory neural origin
      plays a major role in endogenous neurogenic insulin sensitizing mechanisms.

PMID- 12044814
TI  - Glutamine in pediatrics: where next?
AB  - OBJECTIVE: We reviewed the literature and examined the issues surrounding the use
      of glutamine in pediatrics and neonatology. METHODS: We reviewed the literature
      using Medline, Embase, Current Contents, and International Pharmaceutical
      Abstracts. Additional information was obtained from bibliographic citations and
      personal communications. RESULTS: Evidence showed that glutamine levels are
      affected in a number of life stages and conditions. Useful, indicative studies
      are emerging but many fail to demonstrate significant differences. The problems
      of researching in this patient population were demonstrated. CONCLUSION: A need
      for a great deal of further research in this area, including larger multicenter
      trials, clearly emerged.

PMID- 12044815
TI  - Hepatic glutaminase--a special role in urea synthesis?
AB  - OBJECTIVE: To investigate the relationship between hepatic glutaminase and the
      urea cycle with particular reference to the possibility of the existence of a
      metabolic channel between glutaminase and carbamylphosphate synthetase I (CPS-I).
      METHODS: Rat livers were perfused in the non-recirculating mode with 15-N labeled
      ammonia and glutamine. The incorporation of 15-N into nitrogenous products was
      determined by gas chromatography-mass spectrometry. RESULTS: We devised and
      validated a theoretical framework that described the incorporation of the 15-N
      into the various urea mass isotopomers as a function of the isotopic abundance of
      15-N in the two precursor molecules, aspartate and citrulline. We then compared
      the incorporation of 15-N from amino-labeled and amide-labeled glutamine.
      Glucagon activated incorporation of these labels into products, consistent with
      an activation of glutaminase. However, the results indicated no metabolic channel
      between glutaminase and CPS-I. CONCLUSION: We suggest that glutaminase may play a
      role in promoting urea production by virtue of N-acetylglutamate synthesis rather
      than by a channeling mechanism. Glutaminase may provide glutamate, a substrate
      for the synthesis of N-acetylglutamate which is an obligatory activator of CPS-1.

PMID- 12044817
TI  - Nutrition status in patients younger and older than 60 y at hospital admission: a
      controlled population study in 995 subjects.
AB  - OBJECTIVE: Body weight and body mass index are easily obtainable indicators of
      nutrition status but do not provide information on changes in fat-free mass (FFM)
      and fat mass with age. In this prospective controlled study, we investigated
      whether body composition measurements were useful in identifying moderately or
      severely depleted patients, as judged by the Subjective Global Assessment at
      hospital admission. In addition, the subjects were grouped by age (< or =60 and
      >60 y) to determine whether there was an effect of aging on the prevalence of
      malnutrition. METHODS: Nine hundred ninety-five consecutive patients were
      evaluated for malnutrition by body mass index, serum albumin, Subjective Global
      Assessment, and 50-kHz bioelectrical impedance analysis and compared with 995 age
      and height-matched healthy volunteers for FFM and fat mass. RESULTS: A body mass
      index less than 20 kg/m(2) was found in 17.3% of patients. Low albumin (< or
      =34.9 g/L) was found in 14.9% of all patients and 23.7% of those older than 60 y.
      In contrast, 23.1% and 38.3% of all patients were severely and moderately
      depleted, respectively, according to the Subjective Global Assessment. FFM was
      significantly lower in severely depleted men and women and moderately depleted
      women (P < or = 0.001), and fat mass was significantly higher (P < or = 0.05) in
      well-nourished patients than in volunteers. Patients older than 60 y had lower
      FFM and higher fat mass than did patients 60 y or younger or volunteers (P < or =
      0.001). CONCLUSION: The prevalence of malnutrition was greater in patients older
      than 60 y than in those 60 y and younger. Patients classified as severely
      depleted according to the Subjective Global Assessment were depleted of FFM. Body
      composition measurement can help to identify patients with low FFM and high fat
      mass.

PMID- 12044816
TI  - Effects of an alanyl-glutamine-based oral rehydration and nutrition therapy
      solution on electrolyte and water absorption in a rat model of secretory diarrhea
      induced by cholera toxin.
AB  - OBJECTIVES: Recurring diarrhea and persistent diarrhea are commonly associated
      with malnutrition and long-term functional deficits. A beneficial approach would
      be to develop an alanyl-glutamine (AlaGln)-based oral rehydration and nutrition
      therapy (ORNT). We investigated the effect of an AlaGln-ORNT solution on
      electrolyte and water absorption in a rat model of secretory diarrhea induced by
      cholera toxin. METHODS: Phenolsulfonphthalein (50 microg/mL) was used as a non
      absorbable marker for calculation of net water and electrolyte transport.
      Solutions tested were Ringer's solution, a glutamine-based ORNT (Gln-ORNT)
      solution, and an AlaGln-ORNT solution. Cholera toxin (1 microg/mL) was injected
      into lumen of rat small intestinal segments and incubated for 18 h before the
      initiation of the perfusion. RESULTS: Cholera toxin induced significant secretion
      of electrolyte and water in the control Ringer's solution. AlaGln-ORNT and Gln
      ORNT solutions reduced the sodium secretory effect of cholera toxin by 128% and
      36%, respectively. The net water secretion also was reduced by 95% and 60%,
      respectively, with the AlaGln-ORNT and Gln-ORTN solutions. CONCLUSIONS: These
      results showed that AlaGln-ORNT solution can enhance water and electrolyte
      intestinal absorption even better than glutamine or glucose and thus provide a
      potential novel approach for ORNT to break the vicious cycle of diarrhea and
      malnutrition. Clinical trials are now needed in children and adults with diarrhea
      and malnutrition.

PMID- 12044818
TI  - Multivitamin solutions for enteral supplementation: a source of peroxides.
AB  - OBJECTIVE: We investigated whether solutions of enteral vitamin supplementation
      are involved in the generation of peroxides and whether that contamination is
      biologically significant. METHODS: Peroxide contents of oral multivitamin
      preparations were measured over 3 wk after the initial opening of the containers.
      In selected premature infants (younger than 35 wk gestation), urinary peroxides
      were measured after initiating oral multivitamin supplementation. RESULTS:
      Peroxides in multivitamin solutions for enteral use are predominantly organic
      peroxides because they resist catalase. After the initial opening of the
      containers, there was a two-fold increase in total peroxides levels (P < 0.05)
      even in the preparation without riboflavin, a catalyst for the generation of
      peroxides. Initiation of oral vitamin supplementation was associated with
      increased (P < 0.05) urine peroxide levels. The high organic peroxide load did
      not correlate with its urinary excretion, mostly in the form of H(2)O(2). The
      excretion of H(2)O(2) corresponded to its oral intake from the multivitamin
      solution. CONCLUSIONS: Compared with parenteral multivitamin solutions, the
      enteral preparations contained higher organic peroxide levels starting with the
      initial opening of the bottles. The increased urinary excretion of H(2)O(2) after
      enteral multivitamin supplementation suggested a systemic diffusion of peroxides
      or of components of the multivitamin preparation responsible for the generation
      of peroxides. This oxidant load was not quenched by the immature antioxidant
      defenses of premature infants.

PMID- 12044819
TI  - Bioelectrical impedance vector in pre- and postmenarcheal females.
AB  - OBJECTIVE: To present what is to our knowledge the first study of the effects of
      puberty on the distribution of bioimpedance vectors. METHODS: Resistance and
      reactance (standard, tetrapolar analysis at 50-kHz frequency) were measured in
      143 pre- and postmenarcheal Sardinian girls aged 10 to 15 y. RESULTS: The data
      agreed well with the reference values proposed for the Italian population.
      Bioelectrical impedance vector analysis showed a clear differentiation between
      pre- and postmenarcheal girls, whereas no significant age-related differences
      were observed within groups. Postmenarcheal girls had a shorter impedance vector
      (reduced R/H and Xc/H) and a greater phase angle than did premenarcheal girls.
      CONCLUSIONS: Sexual maturity is the major cause of differentiation in the body
      composition of adolescent females. We recommend that this source of variation be
      considered in clinical and anthropologic analyses of bioelectrical variables.

PMID- 12044820
TI  - Role of oral sensory signals in determining meal size in lean women.
AB  - OBJECTIVES: Cognitive restraint exerts a limiting effect on food intake in lean
      individuals. Satiation is the process that determines meal size. Oral, gastric,
      intestinal, and postabsorptive signals might influence this process. I evaluated
      the roles of oral and gastric signals in determining meal size in lean women.
      METHODS: Nine women ate cereal when they felt hungry under baseline and three
      treatment conditions: 1) eating until the pleasantness of the flavor of the
      cereal subsided, 2) eating until the stomach felt full, and 3) eating while
      watching television. The study was done in a normal living environment. The
      amounts of cereal consumed under the four conditions were measured. RESULTS:
      Cereal consumption was similar to that of baseline when the volunteers relied on
      oral signals to terminate the act of eating. Cereal consumption was significantly
      higher than baseline when the volunteers ate until they felt full in the stomach
      and while watching television (P < 0.0001). CONCLUSIONS: Recognition of oronasal
      sensory cues while eating could be the mechanism used by some lean women to limit
      meal size, and this effect can be offset by cognitive distraction.

PMID- 12044821
TI  - Gastrointestinal tolerance of a new infant milk formula in healthy babies: an
      international study conducted in 17 countries.
AB  - OBJECTIVE: We tested the hypothesis that the gastrointestinal tolerance of a new
      infant formula equals or exceeds the tolerance of other milk-based infant
      formulas and compared the tolerance of this new formula with that of human milk.
      METHODS: This prospective, phase IV, open-label study was conducted in 17
      countries. Healthy, full-term infants, 28 to 98 d old, were enrolled on their
      current feeding (no treatment assigned). Feeding regimens included human milk
      (HM), a new infant formula (NF; Similac Advance), other infant formula (OF), HM +
      NF, and HM + OF. Data for stool frequency, stool consistency, and
      gastrointestinal symptoms were collected in study diaries for 2 wk. RESULTS:
      Gastrointestinal tolerance was evaluated in 6999 infants: 979 (14.0%) received
      HM, 1695 (24.2%) received HM + NF, 635 (9.1%) received HM + OF, 2677 (38.2%)
      received NF, and 1013 (14.5%) received OF. Infants fed HM had softer and more
      frequent stools than did those who received NF, HM + NF, or OF (P < 0.001).
      Infants fed NF had softer and more frequent stools than did those fed OF (P <
      0.001), including those fed Enfalac or S-26 (P < 0.001). Regurgitation (P <
      0.001) and colic (P = 0.006) were more frequent with OF than with NF. All feeding
      regimens were well tolerated and only 3.5% of subjects experienced adverse
      events. CONCLUSIONS: This global study demonstrated that stools of infants fed NF
      are softer and more frequent than stools from infants fed OF and are closer to
      those of breast-fed infants. Infants consuming NF also experienced less
      regurgitation and colic than did infants in other feeding groups.

PMID- 12044823
TI  - Glutamine concentration and tissue exchange with intravenously administered alpha
      ketoglutaric acid and ammonium: a dose-response study in the pig.
AB  - OBJECTIVE: We investigated the effects of an intravenous load of alpha
      ketoglutaric acid, ammonium (NH(4)(+)), and metabolic acidosis on plasma
      concentration and splanchnic and hindleg tissue exchange of glutamine, glutamate,
      alanine, and arginine in postabsorptive, anesthetized pigs. METHODS: Sixteen
      anesthetized piglets received a constant infusion of NH(4)Cl for 4 h and alpha
      ketoglutaric acid in incremental dosages for 3 h (group 1, n = 8) or a constant
      infusion of alpha-ketoglutaric acid for 4 h and NH(4)Cl in incremental dosages
      for 3 h (group 2, n = 8). Plasma amino acids were analyzed and splanchnic blood
      flow was calculated according to the indocyanine green dye infusion technique.
      Femoral artery blood flow was measured with ultrasound flowmetry. Statistical
      evaluation of within-group differences was made with the Wilcoxon signed rank
      test. RESULTS: Plasma glutamine levels increased dose-dependently in group 2 (P <
      0.05) but not in group 1. Glutamate concentration increased, mainly in group 2 (P
      < 0.05), whereas the plasma concentration of alanine decreased in both groups (P
      < 0.05). Plasma concentration of arginine increased in both groups (P < 0.05).
      Splanchnic uptake and skeletal muscle release of glutamine did not change in
      either group compared with baseline values. Splanchnic glutamate release
      decreased (P < 0.05) in group 1 at 240 min; muscular uptake was unaffected in
      both groups. Splanchnic uptake and muscular release of alanine were unaffected in
      both groups. The significance level was set at 0.05. CONCLUSION: Our findings
      indicate that the splanchnic bed or hindleg skeletal muscle was not the source of
      the increased plasma concentration of glutamine in this study.

PMID- 12044822
TI  - Effects of a soy protein diet on exercise-induced muscle protein catabolism in
      rats.
AB  - OBJECTIVE: We examined effects of dietary soy protein isolate on muscle calpain
      activity and myosin heavy chain (MHC) degradation in rats performing an acute
      running exercise. METHODS: In rats fed a 20% casein diet, the treadmill running
      exercise, fixed at 80 kg/m, transiently increased calpain activity in
      gastrocnemius muscles in parallel with the release of creatine kinase into
      plasma. The fixed running also caused an accumulation of immunoreactive
      degradation fragments of MHC in the muscle. Feeding a 20% soy protein isolate
      diet as opposed to the control casein diet to rats significantly suppressed the
      running-induced activation of mu- and m-calpains, fragmentation of MHC, and
      release of creatine kinase into plasma (P < 0.05). RESULTS: Rats fed the soy
      protein isolate diet had significantly higher calpastatin activity in
      gastrocnemius muscle than did rats fed the casein diet (P < 0.05), indicating
      that this increase inhibits the exercise-induced autoactivation of calpain.
      Activities of proteasome, cathepsin B + L, and antioxidant enzymes and the levels
      of glutathione and thiobarbituric acid-reactive substances in the muscle did not
      differ between the diet groups at the end of the exercise. CONCLUSIONS: Our
      results suggest that diets containing soy protein prevent exercise-induced
      protein degradation in skeletal muscle, possibly through inhibiting the calpain
      mediated proteolysis.

PMID- 12044824
TI  - S-propyl cysteine reduces the secretion of apolipoprotein B100 and
      triacylglycerol by HepG2 cells.
AB  - A number of sulfur-containing amino acids and peptides are found in allium plants
      such as onion and garlic that have physiologic functions. In HepG2 cells, S
      propyl cysteine decreased the secretion of apolipoprotein B100. The compound
      reduced the secretion of newly synthesized triacylglycerol and cholesterols from
      radiolabeled acetate. We associated the decrease of apolipoprotein B100 secretion
      to the length of the acyl-chain of the sulfur-containing amino acids. The present
      study suggests that foods containing S-propyl cysteine including onions have
      beneficial effects.

PMID- 12044825
TI  - The role of zinc in the growth and development of children.
AB  - This review concerns the importance of zinc in growth, development, and cognitive
      function in children and the deleterious consequences of its deficiency on
      children's health. Possible strategies to overcome zinc deficiency and the
      results of some supplementation trials are discussed.

PMID- 12044827
TI  - Recent advances in the development of infant formulas: mimicking the effects of
      breast feeding.

PMID- 12044826
TI  - Patterns of bioelectrical impedance vector analysis: learning from
      electrocardiography and forgetting electric circuit models.

PMID- 12044828
TI  - Optimal nutrition support (and the demise of the enteral versus parenteral
      controversy).

PMID- 12044829
TI  - Antioxidant activity: are we measuring it correctly?

PMID- 12044830
TI  - Insulin and inflammation: further evidence and discussion.

PMID- 12044831
TI  - Neural-immune gut-brain communication in the anorexia of disease.
AB  - Peripheral administration of toxic bacterial products and cytokines have been
      used to model the immunological, physiological, and behavioral responses to
      infection, including the anorexia of disease. The vagus nerve is the major
      neuroanatomic linkage between gut sites exposed to peripheral endotoxins and
      cytokines and the central nervous system regions that mediate the control of food
      intake, and thus has been a major research focus of the neurobiological approach
      to understanding cytokine-induced anorexia. Molecular biological and
      neurophysiologic evidence demonstrates that peripheral anorectic doses of
      cytokines and endotoxins elicit significant increases in neural activation at
      multiple peripheral and central levels of the gut-brain axis and in some cases
      may modify the neural processing of meal-related gastrointestinal signals that
      contribute to the negative feedback control of ingestion. However, behavioral
      studies of the anorectic effects of peripheral cytokines and endotoxins have
      shown that neither vagal nor splanchnic visceral afferent fibers supplying the
      gut are necessary for the reduction of food intake in these models. These data do
      not rule out 1) the potential contribution of supradiaphragmatic vagal afferents
      or 2) a modulatory role for immune-stimulated gut vagal afferent signals in the
      expression of cytokine and endotoxin-induced anorexia in the intact organism.

PMID- 12044832
TI  - Glucosamine: con or cure?

PMID- 12044833
TI  - Nitric oxide, oxidative stress, and dietary antioxidants.

PMID- 12044836
TI  - Pharmacological profile of hemokinin 1: a novel member of the tachykinin family.
AB  - Recently, the cloning of a novel preprotachykinin gene (PPT-C) has been reported.
      This gene codes for a novel peptide named hemokinin 1 (HK-1). In contrast with
      the known tachykinins, which are exclusively expressed in neuronal tissues, PPT-C
      mRNA was detected primarily in hematopoietic cells. In this study, we
      pharmacologically characterised the effects of HK-1 using three tachykinin
      monoreceptor systems, namely the rabbit jugular vein (rbJV) for NK(1), the rabbit
      pulmonary artery (rbPA) for NK(2), and rat portal vein (rPV) for NK(3) receptors.
      In all these preparations substance P (SP), neurokinin A (NKA) and neurokinin B
      (NKB) elicited concentration dependent contractions showing similar maximal
      effects and the following rank order of potency: SP > NKA = NKB in the rbJV, NKA
      > NKB >> SP in the rbPA, and NKB > NKA > SP in the rPV. In those vessels HK-1
      behaved as a full agonist displaying potencies similar (rbPA and rPV) or slightly
      higher (rbJV) than those of SP. In the rbJV, SR 140333, a selective NK(1)
      receptor antagonist, antagonised the effects of HK-1 and SP with similar high
      potencies (pK(B) 9.3 and 9.5, respectively). Similar results were obtained with
      the pseudopeptide NK(1) antagonist, MEN 11467 (pK(B) 8.8 and 8.6, respectively).
      Taken together, these data indicate that HK-1 behaves as a NK(1) preferring
      receptor agonist.

PMID- 12044837
TI  - Acute ethanol administration downregulates human immunodeficiency virus-1
      glycoprotein 120-induced KC and RANTES production by murine Kupffer cells and
      splenocytes.
AB  - Glycoprotein 120 from HIV-1, HIV-2 and SIV is known to stimulate secretion of
      chemokines by mononuclear cells. Thus, this work tests the hypothesis that acute
      ethanol intoxication suppresses HIV-1 gp120-induced chemokine production by
      murine Kupffer cells and splenocytes. Male Balb/c mice were given ethanol (1.70
      g/Kg) by intragastric gavage in 0.1 ml volume of saline. Five minutes after
      ethanol administration, mice received an intravenous injection of HIV-1 gp120 (5
      microg/Kg). After 24 hr, serum samples, splenocytes and Kupffer cells were
      obtained. Isolated cells were cultured in DMEM for 24 hr to determine production
      of chemokines and cytokines in vitro. Chemokines (MIP-2, KC, RANTES, MIP-1 alpha
      and MCP-1) and cytokines (IL-1 beta, TNF alpha, IL-10, gamma-IFN) were measured
      by ELISA. M-RNA abundance of these mediators was determined by RT-PCR. Results
      show that HIV-1 gp120 treatment was associated with significant elevations in
      serum KC and RANTES. No changes were observed with regard to other chemokines and
      cytokines. Oral administration of ethanol significantly suppressed HIV-1gp120
      induced KC and RANTES release. KC and RANTES-mRNA expression and protein release
      by splenocytes and Kupffer cells were up-regulated by HIV-1 gp120. Such up
      regulation was attenuated by ethanol treatment. These data show that acute
      ethanol administration attenuates HIV-1 gp120-induced chemokine release in vivo
      by isolated splenocytes and Kupffer cells. Through this mechanism, previous in
      vivo ethanol use may compromise the ability of HIV-1 gp120 to induce chemokine
      mediated inhibition of HIV-1 entry into target cells.

PMID- 12044838
TI  - Endomorphins 1 and 2 reduce relaxant non-adrenergic, non-cholinergic
      neurotransmission in rat gastric fundus.
AB  - It is now well established that opioids modulate cholinergic excitatory
      neurotransmission in the gastrointestinal tract. The aim of the present study was
      to characterize a possible effect of endomorphins on nonadrenergic,
      noncholinergic (NANC) relaxant neurotransmission in the rat gastric fundus in
      vitro. The drugs used in the experiments were the endogenous mu-opioid receptors
      (MORs) endomorphin 1 and 2 and the mu-opioid receptor antagonist CTAP (D-Phe-Cys
      Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2). CTAP left the basal tonus and the spontaneous
      activity of the preparation unchanged. Electrical field stimulation (EFS) under
      NANC conditions at frequencies ranging from 0.5 to 16 Hz caused a frequency
      dependent relaxant response on the 5-hydoxytryptamine (5-HT) (10(-7) M)
      precontracted smooth-muscle strip. Both endomorphin 1 and endomorphin 2
      significantly reduced this relaxation in a concentration-dependent manner.
      Endomorphin 1 proved to be more potent in reducing the relaxant responses. The
      endomorphin effects were significantly reversed by the MOR antagonist CTAP. CTAP
      itself did not influence the EFS-induced relaxation. In summary, these data
      provide evidence that the endogenous MOR agonists endomorphin 1 and 2 can reduce
      nonadrenergic, noncholinergic neurotransmission in the rat gastric fundus smooth
      muscle via a pathway involving MORs. The physiological relevance of these
      findings remains to be established, since the data presented suggest that the
      endomorphins act as neuromodulators within NANC relaxant neurotransmission.

PMID- 12044840
TI  - Vascular endothelial dysfunction associated with elevated serum homocysteine
      levels in rat adjuvant arthritis: effect of vitamin E administration.
AB  - We aimed to study the alterations in serum homocysteine levels and endothelium
      dependent and -independent vascular relaxant responses in adjuvant-induced
      arthritis of the rat and to determine the effects of vitamin E administration on
      these changes. Arthritis was induced by a single intradermal injection of
      Freund's complete adjuvant into the paw. 26 days after the induction of
      arthritis, serum homocysteine levels and relaxant responses to acetylcholine and
      sodiumnitroprusside in thoracic aortas were evaluated. The relaxant responses to
      acetylcholine were decreased in aortas from arthritic rats, whereas the responses
      to sodiumnitroprusside were not significantly different when compared to the
      aortas from control rats. A significant increase was observed in serum
      homocysteine levels of the arthritic rats in comparison to those of controls.
      Vitamin E administration (100 mg/kg/day, i.m. for 26 days) to arthritic rats
      resulted in a significant increase in endothelium-dependent aortic responses to
      acetylcholine and a significant decrease in serum homocysteine levels with
      respect to the non-treated arthritic rats. However, in healthy rats, vitamin E
      treatment significantly decreased the acetylcholine-induced relaxant responses.
      We conclude that adjuvant-induced arthritis in the rat is associated with
      increased serum homocysteine levels and this is accompanied by a reduction in
      endothelium-dependent vascular responses in the thoracic aortas. Vitamin E
      treatment leads to normalization of the increased serum homocysteine levels and
      improves the endothelium-dependent relaxant responses in this experimental model.

PMID- 12044839
TI  - Enhanced inhibitory avoidance training protects against the amnesic effect of p
      chloroamphetamine.
AB  - The contribution of acetylcholine (ACh) to memory processing is well documented,
      but it has been proposed that it is not necessary for memory consolidation after
      an enhanced learning experience. It has been suggested that serotonin (5-HT)
      interacts with ACh during memory consolidation, although the nature of this
      interaction is unknown in the case of strong learning. As an initial approach to
      the study of these interactions, we determined whether training of inhibitory
      avoidance using relatively high aversive stimulation protects against the typical
      retention deficits produced by pre-training administration of the 5-HT releaser p
      chloroamphetamine (PCA). Rats were trained after intraperitoneal administration
      of PCA or isotonic saline, using 2.0, 2.5, 3.0 or 3.5 mA and retention of the
      task was measured 24 h later. A significant amnesic state was observed only in
      the PCA groups that had been trained with the two lower intensities. These
      results indicate that 5-HT systems behave similarly to ACh systems, in the sense
      that the amnesic effect produced by interference with their physiological
      activity may be cancelled when animals are submitted to an intense learning
      situation.

PMID- 12044841
TI  - Effect of naturally occurring organosulfur compounds on nitric oxide production
      in lipopolysaccharide-activated macrophages.
AB  - Excessive nitric oxide (NO) production is involved in cellular injury and
      possibly in the multistage process of carcinogenesis. In this study, we
      investigated the effect of organosulfur compounds (S-allyl cysteine, allyl
      sulfide, diallyl disulfide, allyl isothiocyanate, phenyl isothiocyanate, and
      benzyl isothiocyanate) that are found in allium or cruciferous vegetables on NO
      production in J774.1 macrophages activated with lipopolysaccharide (LPS). Diallyl
      disulfide, allyl, phenyl, and benzyl isothiocyanates inhibited NO production, as
      evaluated by nitrite formation at 25 microM. Allyl and benzyl isothiocyanates,
      the most active of the six organosulfur compounds, exhibited dose-dependent
      inhibition and had IC(50) values of 1.6 and 2.7 microM, respectively. Western
      blot analysis suggested that suppression of the induction of inducible NO
      synthase (iNOS) expression is responsible for the inhibition of NO production by
      allyl and benzyl isothiocyanates. In contrast, these isothiocyanates increased
      LPS-stimulated tumor necrosis factor alpha (TNF-alpha) release, suggesting their
      selective action on genes activated by LPS. Our results demonstrate that certain
      organosulfur compounds inhibit NO synthesis in LPS-activated macrophages, and the
      inhibitory effect may be a significant component of their anticarcinogenic
      activity.

PMID- 12044842
TI  - Induction of apoptosis and inhibition of papilloma formation may signal a new
      role for okadaic acid.
AB  - Okadaic acid (OA), a tumor promoter in the mouse skin carcinogenesis model, has
      been shown to induce apoptosis in tumor cell lines that harbor H-ras mutations.
      We examined the effects of OA on mouse keratinocytes with (308) and without (C50)
      H-ras mutation in vitro and in an in vivo system. Following exposure to varying
      concentrations of OA over time, the effects of OA in vitro were assessed using
      microscopic, biochemical and flow cytometric techniques. OA effects on the cells
      included incorporation of propidium iodide, externalization of
      phosphatidylserine, and development of hypodiploidy. 308 cells demonstrated
      typical DNA ladder formation, rapid chromatin and nuclear condensation, while C50
      cells demonstrated delayed chromatin condensation and nuclear fragmentation, but
      no DNA ladder formation. In vivo, OA elicited delayed papilloma formation and
      reduced tumor multiplicity. Though its mechanism of action is not fully known, we
      found that OA-induced inhibition of the clonal expansion of initiated cells may
      be related to the presence or absence of H-ras mutation.

PMID- 12044843
TI  - Beneficial effects of cardiac chymase inhibition during the acute phase of
      myocardial infarction.
AB  - Recently, the presence of the chymase-dependent angiotensin (Ang) II-generating
      system in hamsters, dogs, monkeys, as well as human cardiovascular tissues has
      been identified. We have reported that the activation of cardiac chymase was more
      prominent than that of angiotensin converting enzyme (ACE) and that AT1 receptor
      antagonist treatment rather than ACE inhibitor treatment alone provided
      significant beneficial effects on cardiac function and survival after MI in
      hamsters. The aim of the present study was to determine whether this different
      effects between AT1 receptor antagonist and ACE inhibitor were due to the
      activation of cardiac chymase after MI in hamsters by using 4-[1-[[bis-(4-methyl
      pheny)-methyl]-carbamoyl]-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic
      acid (BCEAB), a novel, orally active and specific chymase inhibitor. The ACE and
      chymase activities in the infarcted left ventricle were significantly increased 3
      days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI
      significantly suppressed the cardiac chymase activity, while it did not affect
      the plasma and cardiac ACE activities 3 days after MI. A significant improvement
      in hemodynamics (maximal negative and positive rates of pressure development;
      left ventricular systolic pressure) was observed for the treatment with BCEAB 3
      days after MI. BCEAB (100 mg/kg/day, p.o.) treatment starting 3 days before MI
      significantly reduced the mortality rate during 14 days of observation following
      MI (vehicle, 61.1%, n = 18; BCEAB, 27.8%, n = 18; P < 0.05). These findings
      demonstrated for the first time that cardiac chymase participates directly in the
      pathophysiologic state after MI in hamsters.

PMID- 12044844
TI  - Differential effects of catecholamines on in vitro growth of pathogenic bacteria.
AB  - Supplementation of minimal medium inoculated with bacterial cultures with
      norepinephrine, epinephrine, dopamine, or isoproterenol resulted in marked
      increases in growth compared to controls. Norepinephrine and dopamine had the
      greatest enhancing effects on growth of cultures of Pseudomonas aeruginosa and
      Klebsiella pneumoniae, while epinephrine and isoproterenol also enhanced growth
      to a lesser extent. The growth of Escherichia coli in the presence of
      norepinephrine was greater than growth in the presence of the three other
      neurochemicals used in the study. Growth of Staphylococcus aureus was also
      enhanced in the presence of norepinephrine, but not to the same degree as was the
      growth of gram negative bacteria. Addition of culture supernatants from E. coli
      cultures that had been grown in the presence of norepinephrine was able to
      enhance the growth of K. pneumoniae. Addition of the culture supernatant fluid
      culture from E. coli cultures that had been grown in the presence of
      norepinephrine did not enhance growth of P. aeruginosa or S. aureus. Culture
      supernatant fluids from bacteria other than E. coli grown in the presence of
      norepinephrine were not able to enhance the growth of any bacteria tested. The
      results suggest that catecholamines can enhance growth of pathogenic bacteria,
      which may contribute to development of pathogenesis; however, there is no uniform
      effect of catecholamines on bacterial growth.

PMID- 12044845
TI  - Salivary cystatins influence ingestion of capsaicin-containing diets in the rat.
AB  - Dietary capsaicin consumed by rats over several days induces cystatin-like
      substances in submandibular saliva. Yet the physiological role of these salivary
      proteins has not been thoroughly investigated. Salivary cystatins in the rat
      submandibular glands are known to be induced by chronic treatment with the
      sympathetic beta-agonist, isoproterenol. In the present study, the possible roles
      of the salivary proteins on food intake were examined by comparing consumption of
      a capsaicin-adulterated (0.05%) diet in rats with and without isoproterenol
      pretreatment (0.1 and 5.0 mg/kg, 5 days). Electrophoretic analysis performed
      prior to feeding trials revealed that the group pretreated with 5 mg/kg
      isoproterenol had large amounts of cystatin in the saliva compared with the group
      pretreated with 0.1 mg/kg isoproterenol and control group. The group treated with
      5 mg/kg isoproterenol showed greater consumption of the capsaicin-adulterated
      diet than the other groups until the 3rd day of trials. Bilateral removal of the
      submandibular and sublingual glands neutralized the effects of isoproterenol.
      Induction of salivary cystatins by isoproterenol treatment was not mimicked by
      systemic and intragastric administration of capsaicin. These results suggest that
      cystatins are included in the salivary proteins induced by capsaicin and that
      they contribute to enhanced ingestion of the capsaicin diet. Induction of
      salivary cystatins may be triggered by irritation of the oral mucosa by
      capsaicin.

PMID- 12044847
TI  - Ultrasonographic prediction of patients' outcome in hyperacute ischemic stroke.
AB  - OBJECTIVE: We examined whether carotid ultrasonographic (US) findings in
      hyperacute ischemic stroke are useful to predict patients' outcome. METHODS: We
      studied 73 consecutive patients with carotid stroke using both computed
      tomography (CT) and duplex carotid ultrasonography within 6 h of stroke onset. We
      evaluated early CT findings defined as obscuration of the lentiform nucleus, loss
      of the insular ribbon and/or cortical effacement, and US findings indicating
      internal carotid artery (ICA) or middle cerebral artery trunk occlusion. The
      National Institute of Health Stroke Scale (NIHSS) at admission and modified
      Rankin scale on day 30 were assessed. RESULTS: According to multiple logistic
      regression analysis, positive US findings (P = 0.0045, odds ratio, 11.1) provided
      the best predictor of modified Rankin scale score > or =3 compared with a
      baseline NIHSS> or =16 (P = 0.036, odds ratio, 7.9) and early CT findings (P =
      0.18). CONCLUSION: US findings of hyperacute stroke may provide a better
      predictor of patients' outcome.

PMID- 12044846
TI  - Protection of oxidative damage by aqueous extract from Antrodia camphorata
      mycelia in normal human erythrocytes.
AB  - Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional
      Chinese medicine. The purpose of this study was to evaluate the ability of
      aqueous extract from A. camphorata mycelia to protect normal human erythrocytes
      against oxidative damage in vitro. Oxidative hemolysis and lipid/protein
      peroxidation of erythrocytes induced by the aqueous peroxyl radical [2,2'
      Azobis(2-amidinopropane) dihydrochloride, AAPH] were suppressed by A. camphorata
      mycelia in a time-and concentration-dependent manner. A. camphorata mycelia also
      prevented the depletion of cytosolic antioxidant glutathione (GSH) and ATP in
      erythrocytes. Moreover, cultured human endothelial cell damage induced by AAPH
      was suppressed by A. camphorata mycelia. Interestingly, A. camphorata mycelia
      exhibited significant cytotoxicity against leukemia HL-60 cells but not against
      cultured human endothelial cells. These results imply that A. camphorata mycelia
      may have protective antioxidant and anticancer properties.

PMID- 12044848
TI  - Which Doppler velocity is best for assessing suitability for carotid
      endarterectomy?
AB  - OBJECTIVE: To evaluate which velocity, or combination of velocities, from carotid
      Doppler ultrasonography (DU), achieved the closest agreement with an assessment
      of suitability for carotid endarterectomy from intra-arterial angiograms (IAA).
      METHODS: We prospectively collected data from 148 consecutive patients (288
      carotids), who had DU and IAA (blinded assessment) before possible carotid
      endarterectomy. We halved our data by randomly selecting the left or right
      carotid artery for each patient. We used one half to calibrate our DU results to
      IAA (to decide which velocity corresponded with what degree of angiographic
      stenosis). Using this analysis, each artery in the other half of the data was
      defined as suitable (80-99% stenosed) or unsuitable for carotid endarterectomy.
      We evaluated every individual, and combination of, velocities (strategies) to see
      which gave the closest agreement with IAA. RESULTS: Of all 80 strategies, six
      resulted in better agreement than others of the same or lower complexity. Five of
      these strategies gave better agreement than the internal carotid artery peak
      systolic velocity (ICA PSV) (kappa 0.78), but the improvement was small.
      CONCLUSION: Using the ICA PSV alone is adequate for assessing carotid stenosis
      before endarterectomy using DU, as long as the machine is calibrated to IAA.
      However, the addition of the ratio of the ICA PSV to the common carotid artery
      PSV adds only one further measurement, slightly increases the agreement with IAA,
      and would be reasonable to use on a daily basis.

PMID- 12044849
TI  - Asymptomatic embolisation in non-valvular atrial fibrillation and its
      relationship to anticoagulation therapy.
AB  - OBJECTIVE: A prospective study to determine the prevalence of embolic signals
      (ES) detected with transcranial Doppler ultrasound (TCD) in subjects with non
      valvular atrial fibrillation (NVAF) who were and were not taking anticoagulants.
      METHODS: Sixty-eight subjects with NVAF taking warfarin and sixty-three NVAF
      subjects not taking warfarin were recruited from the cardiology department. No
      patients had suffered a previous stroke or clinical systemic embolisation. Thirty
      subjects in sinus rhythm were recruited as controls. TCD recordings were
      performed bilaterally from the middle cerebral arteries for 1 h. In 126 subjects
      (96%) the recording was repeated 1 week later. All Doppler recordings were
      reviewed blindly by an observer for ES. RESULTS: After one recording ES were
      detected in one warfarin NVAF subject (1.5%), four non-warfarin NVAF subjects
      (6.3%) and no sinus rhythm controls. Following both recordings ES were detected
      in one warfarin NVAF subject (1.5%) and seven non-warfarin NVAF subjects (11.9%)
      P = 0.017. CONCLUSIONS: Asymptomatic ES can be detected in a minority of subjects
      with NVAF. These signals were significantly less common in NVAF subjects taking
      warfarin, and this is consistent with asymptomatic ES having clinical
      significance in this disease. TCD detection of ES may have application in
      patients with NVAF for risk stratification, and assessment of the efficacy of new
      anti-platelet and anti-thrombotic regimens in the condition. Further large
      prospective studies are required to determine whether ES predict stroke risk in
      this patient group.

PMID- 12044850
TI  - Food allergy and intolerance: response to intestinal provocation monitored by
      endosonography.
AB  - OBJECTIVE: Objective assessment of adverse reactions to food is a long-felt want.
      We report our preliminary experience with a new endosonographic allergen
      provocation test. METHODS: Twenty patients were examined, seven patients having
      food allergy and 13 having food intolerance. The duodenal mucosa was challenged
      with allergen extracts via a nasoduodenal tube. The responses were recorded using
      a miniprobe for endosonography through the tube. Thereafter, intestinal lavage
      was performed by giving 2 l PEG solution containing micro Ci (51)CrEDTA. The gut
      lavage fluid and urine for 5 h were collected. RESULTS: Increased mucosal
      thickness in response to provocation was recorded in 11 patients, but not more
      often or pronounced in the allergic than in the intolerance group. Interestingly,
      increased mucosal thickness associated with a new echogenic layer was seen in two
      patients and a sustained duodenal contraction, lasting 15-20 min associated with
      pain, in another two. Intestinal permeability and inflammatory mediators were not
      significantly different in the two groups. CONCLUSION: In patients with self
      reported adverse reactions to food abnormal responses to duodenal provocation may
      be recognised by endosonography. However, neither endosonography nor intestinal
      permeability or faecal calprotectin responses were able to distinguish between
      food allergy and intolerance. Sustained duodenal contractions in response to food
      might be a cause of abdominal pain.

PMID- 12044851
TI  - Comparison of the SonoSite and Acuson 128/XP10 ultrasound machines in the 'bed
      side' assessment of the post liver transplant patient.
AB  - Hepatic artery thrombosis after liver transplant is associated with biliary
      sepsis and irretrievable loss of the graft. Early identification of hepatic
      artery thrombosis, using a 'high-specification' ultrasound machine incorporating
      spectral Doppler, is crucial to patient management in the postoperative period
      with portable ultrasound as the first line of investigation for evaluation of the
      hepatic artery. We evaluated the efficacy of the SonoSite portable ultrasound
      machine, which uses power Doppler only, in the evaluation of the post transplant
      hepatic artery. An Acuson 128/XP10 ultrasound machine was used as the comparison
      'reference-standard' with identification of the hepatic artery by both colour and
      spectral Doppler trace. The SonoSite accurately identified the hepatic artery in
      88.4% of patients with power Doppler. The SonoSite was easier to transport and
      manage at the bedside leading to considerable time saving. In 11.6% of patients a
      repeat ultrasound using the 'reference-standard' machine would be necessary.

PMID- 12044852
TI  - Subepithelial masses of the gastrointestinal tract evaluated by endoscopic
      ultrasonography.
AB  - OBJECTIVES: To diagnose and characterize subepithelial lesions of the
      gastrointestinal (GI) tract using endoscopic ultrasonography (EUS) and search for
      markers of malignancy in stromal cell tumors. METHODS: Fifty-four patients with
      suspected subepithelial lesions at endoscopy were examined using miniature
      ultrasound probes, integrated ultrasound endoscopes, or both. Surgical treatment
      was considered if a solid lesion had a maximum diameter of at least 3 cm, mixed
      echogenicity, or an ill-defined or irregular border. RESULTS: EUS disclosed 37
      solid lesions and ten fluid-filled structures. In seven patients, including two
      with protrusion from a normal spleen, no pathology could be demonstrated.
      Thirteen patients were operated and 41 were observed clinically with (n = 9) or
      without EUS (n = 32) for a median follow-up period of 36 months. Twenty-three
      patients had an intramural stromal cell tumor. None of these were malignant, but
      increased mitotic activity was found in two medium-sized resected tumors with
      mixed echogenicity and bleeding lesions of the endoluminal surface. CONCLUSION:
      EUS can detect and characterize subepithelial masses in the GI tract. Pathologic
      lesions of the overlying mucosa may indicate malignant development in stromal
      cell tumors, but valid markers of malignant potential are still lacking.

PMID- 12044853
TI  - The effectiveness of combined clinical-sonographic screening in the treatment of
      neonatal hip instability.
AB  - OBJECTIVE: The early diagnosis of neonatal hip instability is well recognized in
      preventing possible late developmental dysplasia of the hip. The optimal scheme
      of its diagnosis is essential. The role of combined approach of clinical and
      ultrasonographic evaluation of hip instability in newborns is evaluated in the
      present study. METHODS: Hips of 9030 consecutive neonates were examined
      independently by clinical and ultrasonographic means, separately by
      neonatologists and orthopedic surgeons, without initial sharing of information.
      When hip pathology was diagnosed by one of the modalities and missed by another,
      re-examination was performed. The rate of initially undiagnosed, clinically or
      ultrasonographically unstable hips and the 1-year follow up of the effected
      newborns were recorded. RESULTS: Instability was diagnosed in 1.4% of all hips,
      but only 63% of unstable hips were diagnosed on the initial clinical examination.
      In the remainder, the clinical pathology was established on clinical re
      examination after the sonographic abnormality was recognized. Similarly, but to a
      much lesser extent, sonographic pathology was detected only on the re-examination
      in 5% of the clinically unstable hips. Although the overall initial under
      diagnosis rate of hip instability was 0.6% of all hips, the rate for treated hips
      was 0.1%. CONCLUSION: These data should be taken into consideration in planning
      an efficient DDH screening policy.

PMID- 12044854
TI  - Postoperative fistula of the abdominal wall after laparascopic cholecystectomy
      due to lost gallstones.
AB  - Abdominal fistula caused by cholesterol gallstones, which remained in the
      abdominal wall after laparascopic cholecystectomy: a laparascopic cholecystectomy
      was performed in a 60-years-old man who was diagnosed as acute necrosing
      cholecystitis due to cholecystolithiasis. After removal of the gallbladder using
      an Endocath some gallstones remained in the excision channel of the abdominal
      wall. Therefore, a fistula developed in the excision channel postoperatively. As
      the wound healing was disturbed an investigation of the abdominal wall was
      performed by ultrasound. In the former excision channel several small, oval,
      formations with high echogenicity and faint ultrasound shadows were detected,
      corresponding to additional gallstones. After excision of granulation tissue and
      removal of the cholesterol stones, complete healing of the fistula in the
      abdominal wall was achieved.

PMID- 12044855
TI  - Subcutaneous needle-tract seeding after fine needle aspiration biopsy of
      pancreatic liver metastasis.
AB  - A case of subcutaneous neoplastic seeding after fine needle aspiration biopsy of
      a pancreatic liver metastasis is reported. Neoplastic seeding is a rare
      complication after fine needle biopsy (FNB). The seeding appeared 3 months after
      the biopsy with a subcutaneous hypoechoic nodule; diagnosis was confirmed by fine
      needle aspiration of the nodule. The neoplastic seeding did not change the
      outcome of the patient.

PMID- 12044856
TI  - Meckel Gruber syndrome: a first trimester diagnosis of a recurrent case.
AB  - We report of a case of Meckel Gruber Syndrome (MGS) in a woman, who suffered
      previously from a pregnancy with the same disorder. MGS, consisting of an
      occipital encephalocele, bilateral cystic kidneys and postaxial polydactyly, is a
      rare autosomal recessive disorder, with a recurrence risk of 25%. With the
      present technology, a targeted ultrasound in the late embryonic or early fetal
      stages of pregnancy has the potential to diagnose this syndrome. Clinical
      screening in further pregnancies is of utmost importance and the management of
      such cases is presented.

PMID- 12044857
TI  - Colonic perforation and abscess following radiofrequency ablation treatment of
      hepatoma.
AB  - OBJECTIVE: Radiofrequency (RF) has been demonstrated as a relatively safe
      procedure in the treatment of hepatocellular carcinoma (HCC). METHODS: A 60-year
      old man with liver cirrhosis presented with a large, infiltrating HCC close to
      the right colon. The patient was treated with internally cooled RF. RESULTS: On
      the 8th day post-ablation, a complication of right colon perforation was
      diagnosed. CONCLUSION: RF can induce untoward thermal damage, and may not be
      indicated in large infiltrating lesions abutting the gastrointestinal tract.

PMID- 12044858
TI  - Optimal set-up for ultrasound guided punctures using new scanner applications: an
      in-vitro study.
AB  - OBJECTIVE: To investigate if US-visualisation of the needle tip echo during US
      guided punctures could be improved by use of new technological applications.
      METHOD: an US-guided 18 G Trocar needle was inserted into targets of a puncture
      phantom. The punctures were performed in series of 10 using different settings of
      the US-scanner (GE Logic 700 Expert). At 7-cm of puncture depth the quality of
      the echo was tested using four different settings; normal (N), N + automatic
      tissue optimising (ATO), coded harmonic imaging (CHI), CHI + ATO and at 13-cm of
      puncture depths six different settings; N, N + ATO, coded excitation (CE),
      CE+ATO, CHI, CHI+ATO. In total 100 (40 + 60) images were randomly numbered and
      read independently by three radiologists with regard to scoring of the quality of
      the echoes from the needle tip, needle shaft and the target. RESULTS: US
      visualisation of the needle tip was significantly (P < 0.005) improved as
      compared to normal settings (N) when the settings of ATO and CE were used. CHI
      resulted in the lowest score. A high agreement between observers was registered.
      Similar results were registered with regard to scorings from the needle shaft and
      target. CONCLUSION: Not only changes of needle designs and puncture techniques
      can enhance echoes from the needle but also changes in the settings of the US
      scanner with the use of new technological applications can improve visualisation
      of the needle echo.

PMID- 12044859
TI  - Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a
      near infrared spectroscopy and transcranial Doppler study.
AB  - OBJECTIVE: To investigate the effect of vinpocetine on cerebral blood flow (CBF)
      in the compromised circulation of a stroke affected hemisphere using transcranial
      Doppler (TCD) and near infrared spectroscopy (NIRS) methods. METHODS: 43 patients
      with ischemic stroke were randomized into vinpocetine (VP) and placebo group in a
      double blind, placebo-controlled study of the effect of a single-dose i.v.
      infusion of vinpocetine on cerebral blood perfusion and oxygenation. In the VP
      group 20 mg VP in 500 ml saline, in the placebo group 500 ml saline alone were
      administered. The concentrations of oxy-, reduced- and total hemoglobin were
      measured by NIRS frontolaterally on the side of lesion while the mean cerebral
      blood flow velocity (CBFV), the pulsatility index (PI) and Doppler spectral
      intensity (DSI) were monitored by TCD in the middle cerebral artery on the same
      side. Values were averaged for the first 5 min prior to the infusion and for the
      last 5 min of infusion and they were compared between groups. RESULTS: The
      concentration of all three chromophores increased during infusion in the VP group
      (mean dHbT = 1.03, CI(95) = 0.84, P = 0.058; mean dHbO = 0.92, CI(95) = 0.91, P =
      0.071; mean dHb = 0.10, CI(95) = 0.21, P = 0.297). The HbT and HbO showed a
      substantially smaller increase in the placebo group (mean dHbT = 0.31, CI(95) =
      0.74, P = 0.22; mean dHbO = 0.57, CI(95) = 0.80, P = 0.094) while the Hb
      decreased (mean dHb = -0.26, CI(95) = 0.29, P = 0.05). Comparing to the placebo
      group Hb increased significantly in the VP group (P = 0.027) while the increase
      of HbO and HbT did not reach the level of significance (P = 0.29 and 0.11). DSI
      showed a significantly larger increase in the VP than in placebo group (dDSI=25.8
      CI(95)=8.8 [VP]; dDSI =3.3, CI(95) = 3.7 [Placebo], P < 0.005). The CBFV and PI
      did not differ significantly between groups. (dVm = 5.0+/-2.98 cm/s [VP], dVm =
      4.1+/-2.57 cm/s [Placebo], P = 0.28; dPI = 0.08 [VP], dPI = 0.09 [Placebo]; P =
      0.47). CONCLUSION: VP increases cerebral perfusion and parenchymal oxygen
      extraction as well. The increased perfusion was indicated by NIRS and by TCD
      measurement of DSI while conventional velocity and pulsatility measurements
      failed to detect theses effects. NIRS is a sensitive, feasible method of
      measuring changes in regional blood flow and tissue oxygenation in the
      superficial cortex.

PMID- 12044860
TI  - A 3D model of the voltage-dependent anion channel (VDAC).
AB  - Eukaryotic porins are a group of membrane proteins whose best known role is to
      form an aqueous pore channel in the mitochondrial outer membrane. As opposed to
      the bacterial porins (a large family of protein whose 3D structure has been
      determined by X-ray diffraction), the structure of eukaryotic porins (also termed
      VDACs, voltage-dependent anion-selective channels) is still a matter of debate.
      We analysed the secondary structure of VDAC from the yeast Saccharomyces
      cerevisiae, the fungus Neurospora crassa and the mouse with different types of
      neural network-based predictors. The predictors were able to discriminate
      membrane beta-strands, globular alpha-helices and membrane alpha-helices and
      localised, in all three VDAC sequences, 16 beta-strands along the chain. For all
      three sequences the N-terminal region showed a high propensity to form a globular
      alpha-helix. The 16 beta-strand VDAC motif was thus aligned to a bacterial porin
      derived template containing a similar 16 beta-strand motif. The alignment of the
      VDAC sequence with the bacterial porin sequence was used to compute a set of 3D
      coordinates, which constitutes the first 3D prediction of a eukaryotic porin. All
      the predicted structures assume a beta-barrel structure composed of 16 beta
      strands with the N-terminus outside the membrane. Loops are shorter in this side
      of the membrane than in the other, where two long loops are protruding. The shape
      of the pore varies between almost circular for Neurospora and mouse and slightly
      oval for yeast. Average values between 3 and 2.5 nm at the C-carbon backbone are
      found for the diameter of the channels. In this model VDAC shows large portions
      of the structure exposed on both sides of the membrane. The architecture we
      determine allows speculation about the mechanism of possible interactions between
      VDAC and other proteins on both sides of the mitochondrial outer membrane. The
      computed 3D model is consistent with most of the experimental results so far
      reported.

PMID- 12044861
TI  - Identification of catalytically important amino acids in human ceruloplasmin by
      site-directed mutagenesis.
AB  - The involvement of amino acid residues previously proposed on the basis of
      structural data to have roles in the ferroxidase and diamine oxidase activities
      of human ceruloplasmin was investigated. Variants of human ceruloplasmin, in
      which residues proposed to be involved in electron transfer and/or iron-binding
      had been altered by site-directed mutagenesis, were expressed in HEK293 cells.
      E633A and E597A/H602A variants exhibited reduction in both activities by 50-60%
      compared to recombinant wild-type ceruloplasmin. The variant E935A/H940A had
      reduced ferroxidase activity (50%) but unaltered diamine oxidase activity,
      whereas the variant E971A exhibited enhanced diamine oxidase activity. For the
      L329M variant, both activities were identical to those of wild-type
      ceruloplasmin.

PMID- 12044862
TI  - Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate
      dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A
      resolution.
AB  - The structure of the glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH)
      from Trypanosoma cruzi complexed with chalepin, a natural product from Pilocarpus
      spicatus, has been determined by X-ray crystallography to 1.95 A resolution. The
      structure is in the apo form without cofactors in the subunits of the tetrameric
      gGAPDH in the asymmetric unit. Unequivocal density corresponding to the inhibitor
      was clearly identified in one monomer. The final refined model of the complex
      shows extensive conformational changes when compared with the native structure.
      The mode of binding of chalepin to gGAPDH and its implications for inhibitor
      design are discussed.

PMID- 12044863
TI  - Progression of dystrophic features and activation of mitogen-activated protein
      kinases and calcineurin by physical exercise, in hearts of mdx mice.
AB  - We have previously demonstrated that calcineurin and p38 mitogen-activated
      protein kinase (MAPK) are up-regulated in the hearts of mdx mice. However, the
      degree of up-regulation observed was variable, which may reflect variable levels
      of daily physical activities among the mice. To investigate whether or not
      exercise affects dystrophic features and activates intracellular signaling
      molecules in mdx hearts, we subjected mdx and C57BL/10 mice to treadmill exercise
      and examined intracellular signaling molecules in cardiac muscles, at the protein
      level. The heart to body weight ratio was significantly increased in exercised
      mdx mice. Histopathology in exercised mdx hearts showed extensive infiltration of
      inflammatory cells, together with increases in interstitial fibrosis and adipose
      tissues, all of which were not observed either in exercised C57BL/10 or non
      exercised mdx hearts. Phosphorylated p38 MAPK, phosphorylated extracellular
      signal-regulated kinase 1/2 and calcineurin, but not phosphorylated c-Jun N
      terminal kinase 1, were up-regulated in exercised mdx hearts compared to
      exercised C57BL/10 or non-exercised mdx hearts. These data suggest that physical
      exercise accelerates the dystrophic process through activation of intracellular
      signaling molecules in dystrophin-deficient hearts.

PMID- 12044864
TI  - Detection of a very rapid first phase in complex formation of DnaK and peptide
      substrate.
AB  - Complex formation of the Hsp70 chaperone DnaK with the fluorescence-labeled
      peptide ALLLSAPRR shows a very rapid first phase that has as yet not been
      observed with other peptides. This first phase is completed within the dead time
      (1-2 ms) of the stopped-flow instrument and corresponds to two thirds of the
      total increase in fluorescence. It occurs both in the presence and in the absence
      of ATP and is followed by a fast, a slow and a very slow step. These binding
      kinetics that are vastly different from those observed with other peptides might
      indicate the existence of a second substrate-binding site of DnaK.

PMID- 12044865
TI  - Identification of o-quinone/quinone methide metabolites of quercetin in a
      cellular in vitro system.
AB  - Formation of quercetin quinone/quinone methide metabolites, reflected by
      formation of the glutathionyl quercetin adducts as authentic metabolites, was
      investigated in an in vitro cell model (B16F-10 melanoma cells). Results of the
      present study clearly indicate the formation of glutathionyl quercetin adducts in
      a tyrosinase-containing melanoma cell line, expected to be representative also
      for peroxidase-containing mammalian cells and tissues. The data obtained also
      support that the adducts are formed intracellular and subsequently excreted into
      the incubation medium and reveal for the first time evidence for the pro
      oxidative metabolism of quercetin in a cellular in vitro model.

PMID- 12044866
TI  - A novel striated tropomyosin incorporated into organized myofibrils of
      cardiomyocytes in cell and organ culture.
AB  - Striated muscle tropomyosin is classically described as consisting of 10 exons,
      1a, 2b, 3, 4, 5, 6b, 7, 8, and 9a/b, in both skeletal and cardiac muscle. A novel
      isoform found in embryonic axolotl heart maintains exon 9a/b of striated muscle
      but also has a smooth muscle exon 2a instead of exon 2b. Translation and
      subsequent incorporation into organized myofibrils, with both isoforms, was
      demonstrated with green fluorescent protein fusion protein construct. Mutant
      axolotl hearts lack sufficient tropomyosin in the ventricle and this
      smooth/striated chimeric tropomyosin was sufficient to replace the missing
      tropomyosin and form organized myofibrils.

PMID- 12044867
TI  - Variant forms of upstream stimulatory factors (USFs) control the promoter
      activity of hTERT, the human gene encoding the catalytic subunit of telomerase.
AB  - It is known that Myc regulates the expression of TERT, the telomerase catalytic
      subunit gene, by binding to E box. Here we show that another E box-binding
      protein, upstream stimulatory factor (USF), also regulates TERT expression.
      Specifically, the N-terminally truncated form of USF2 is present in telomerase
      negative/resting human lymphocytes, but not in telomerase
      positive/phytohemagglutinin-activated lymphocytes. In electrophoretic mobility
      shift assay, both full-length and truncated USF2s bound to the TERT E box. In a
      transient expression assay, the truncated USF had a dominant-negative effect on
      both exogenous full-length USF and endogenous positive regulators for activating
      TERT expression. These results suggest that the differential abundance of
      truncated USF2 may regulate telomerase activity during lymphocyte activation.

PMID- 12044868
TI  - Insulators prevent transcriptional interference between two promoters in a double
      gene construct for transgenesis.
AB  - In transgenesis, the expression of two transgenes is often subject to mutual
      interference by each of the two expression cassettes when they are driven by
      different transcriptional regulatory elements in a single construct. To study
      this problem, we constructed vectors consisting of two expression units, one
      contains a strong ubiquitous promoter and the other contains a tissue-specific
      transcriptional element. The expression pattern of each transgene was examined in
      transfected cell lines and also in transgenic mice. In both cases, two expression
      units in a single construct were expressed in an independent manner and were
      controlled by their respective regulatory element only if we placed insulators at
      both ends of one expression unit. These results indicate that usage of insulators
      is a valuable tool for transfection of double gene constructs in transgenesis.

PMID- 12044869
TI  - Pretreatment with salicylic acid primes parsley cells for enhanced ion transport
      following elicitation.
AB  - Pretreatment with salicylic acid (SA), an inducer of plant disease resistance,
      enhanced the capacity of parsley cells for the induction of a rapid K(+)/pH
      response and the subsequent coumarin (phytoalexin) secretion. In SA-primed cells,
      a low elicitor dose induced these two responses to a similar extent as did a high
      elicitor dose in non-primed cells. These observations suggest that the SA
      mediated augmentation of the early K(+)/pH response may contribute to the
      enhancement of subsequent coumarin secretion. As the amphotericin B-induced
      K(+)/pH response was not enhanced in SA-primed cells, it is concluded that
      signaling components that are improved by priming are located between elicitor
      signal perception and the plasma membrane transporters mediating the K(+)/pH
      response.

PMID- 12044870
TI  - Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by
      TNF-alpha in brown adipocytes.
AB  - Extracellular regulated kinases (ERKs) mediate the inhibitory effect of tumor
      necrosis factor alpha (TNF-alpha) on uncoupling protein-1 (UCP-1), but not on
      lipid accumulation. TNF-alpha-induced ERK-dependent peroxisome proliferator
      activator receptor gamma (PPAR gamma) phosphorylation could be responsible for
      UCP-1 downregulation. Thus, the negative effect of TNF-alpha on UCP-1 mRNA
      expression at 4-5 h, under basal conditions or in cells treated with the PPAR
      gamma agonist, rosiglitazone, was reversed by the MEK1 inhibitor PD98059. In
      contrast, fatty acid synthase and malic enzyme mRNA downregulation was not
      prevented. Moreover, rosiglitazone has no positive effect on adipogenic gene
      expression or lipid accumulation. Therefore, there is a differential regulation
      of thermogenic and adipogenic differentiation by PPAR gamma, which might account
      for the differences in the TNF-alpha regulation through ERKs.

PMID- 12044871
TI  - The ATP-binding cassette (ABC) transporter Bpt1p mediates vacuolar sequestration
      of glutathione conjugates in yeast.
AB  - Vacuolar sequestration or cellular extrusion of glutathione-conjugated
      xenobiotics and catabolites by ATP-binding cassette (ABC) transporters is an
      important detoxification mechanism operating in many species. In this study, we
      show that the yeast ABC transporter Bpt1p, a paralogue of Ycf1p, acts as an ATP
      dependent vacuolar pump for glutathione conjugates. Bpt1p, which is inhibited by
      vanadate and glibenclamide, accounts for one third of the total vacuolar
      transport of glutathione conjugates. Furthermore, immunoblot analyses show that
      Bpt1p levels are strongly elevated in early stationary phase, consistent with a
      function of Bpt1p in vacuolar detoxification.

PMID- 12044872
TI  - Group B streptococcus (GBS) modifies macrophage phosphatidylserine metabolism
      during induction of apoptosis.
AB  - Group B streptococcus (GBS) induced macrophage apoptosis by which it could avoid
      host defence mechanisms. Macrophages, which constitutively express
      phosphatidylserine (PtdSer) on the outer leaflet of plasma membrane, increased
      PtdSer exposure during GBS-induced apoptosis. Induction of apoptosis decreased
      PtdSer radioactivity of macrophages incubated with [(3)H]serine. The effect
      appeared not due to increasing conversion of PtdSer to phosphatidylethanolamine
      or phosphatidylcholine nor to the release of radioactive membrane vesicles. The
      radioactivity in lysoPtdSer was also reduced. These results confirm that
      induction of apoptosis involves a modification of PtdSer metabolism and point out
      the typical features of the GBS-induced apoptosis with respect to other models of
      apoptosis.

PMID- 12044873
TI  - Deletion of nine carboxy-terminal residues of the Rubisco small subunit decreases
      thermal stability but does not eliminate function.
AB  - A recent X-ray crystal structure of ribulose-1,5-bisphosphate
      carboxylase/oxygenase from the green alga Chlamydomonas reinhardtii lacks 13
      carboxy-terminal residues of the small subunit. To determine the importance of
      this divergent region, a non-sense mutation was created that removes nine
      residues. This engineered gene was transformed into a Chlamydomonas strain that
      lacks the small-subunit gene family. The resulting holoenzyme has a normal
      CO(2)/O(2) specificity but decreased carboxylation V(max). Whereas wild-type
      enzyme retained most of its carboxylase activity after a 10-min incubation at 55
      degrees C, the mutant enzyme was inactivated. Thus, although disordered or
      divergent, the carboxy terminus is required for maximal activity and stability.

PMID- 12044874
TI  - The effect of an agglutogen on virus infection: biotinylated filamentous phages
      and avidin as a model.
AB  - To address the effect of an agglutogen on virus infection, we studied the avidin
      associated inhibition of infection by biotinylated M13 phages (BIO-phages).
      Microscopic observation of mixtures of BIO-phages and avidin-fluorescein
      conjugates revealed many aggregates. Even at low phage concentrations, avidin
      induced inhibition of infection significantly. Anti-M13 phage antibody also made
      aggregates and inhibited the infection but in a different manner from avidin. The
      inhibition by avidin was at > or = 2 microg/ml, time dependent and marked until
      10 min after the mixing of the BIO-phages and Escherichia coli. On the other
      hand, antibody inhibited the infection at > or = 0.1 microg/ml dose dependently,
      and the inhibition was time dependent and marked until 45 min after the mixing at
      moderate and low phage concentrations. These results indicate that avidin against
      BIO-phages and antibodies are agglutogens, and the inhibition of the BIO-phages
      by avidin is closely related to the tetramerization of avidin. Agglutogens may be
      novel alternative antiviral drugs.

PMID- 12044875
TI  - Induced chirality upon binding of cis-parinaric acid to bovine beta
      lactoglobulin: spectroscopic characterization of the complex.
AB  - Binding of the polyunsaturated cis-parinaric acid to bovine beta-lactoglobulin
      (BLG) was studied by circular dichroism (CD), electronic absorption spectroscopy
      and mass spectrometry methods. Upon protein binding, the UV absorption band of
      parinaric acid is red shifted by ca. 5 nm, showing hypochromism and reduced
      vibrational fine structure, suggesting that the ligand binds as a monomer in non
      planar geometry. In the CD spectra measured at pH 7.36 and 8.5 a strong, negative
      Cotton band appears centered at 310 nm (Delta epsilon = -25 M(-1) cm(-1))
      corresponding to the long-wavelength absorption band of cis-parinaric acid. The
      source of this induced optical activity is the helical distortion of the polyene
      chromophore caused by the chiral protein environment. From CD spectral data the
      value of the association constant was calculated to be 4.7 x 10(5) M(-1) at pH
      7.36. CD and mass spectrometry measurements showed that parinaric acid binds
      weakly to BLG in acidic solution, though small peaks at mass 18,559 and 18,645
      can be obtained in the reconstructed electrospray mass spectrum; these correspond
      to the binding of parinaric acid in 1:1 stoichiometry to both monomer variants of
      BLG B and A. The hydrophobic interior cavity of BLG was assigned as the primary
      binding site of cis-parinaric acid.

PMID- 12044876
TI  - Biochemical properties of the human REV1 protein.
AB  - It has been proposed that the REV1 protein plays an important role in the induced
      mutagenesis pathway. We show that purified REV1 protein inserts dCMP opposite
      template G, A, T and C, and dGMP and dTMP opposite template G in the presence of
      magnesium, while in the presence of manganese the specificity for dCMP was found
      to be relaxed and the REV1 protein acquired the ability to insert dCMP, dGMP,
      dAMP and dTMP opposite templates G, A, T, and C. Kinetic analysis provided
      evidence for high affinity for dCTP with template G, suggesting that the REV1
      protein is specialized for dCTP and template G.

PMID- 12044877
TI  - cIAP-1, but not XIAP, is cleaved by caspases during the apoptosis induced by TGF
      beta in fetal rat hepatocytes.
AB  - We have studied the expression of XIAP, cIAP-1 and cIAP-2 in fetal rat
      hepatocytes and its possible regulation by pro-apoptotic stimuli (transforming
      growth factor-beta (TGF-beta)) and survival signals (epidermal growth factor
      (EGF)). The three forms of inhibitor of apoptosis proteins (IAPs) are expressed
      in fetal hepatocytes and only cIAP-1, but not XIAP or cIAP-2, is cleaved during
      TGF-beta-induced apoptosis. The pan-caspase inhibitor Z-VAD.fmk blocked this
      effect, which indicates that cIAP-1 is a caspase substrate. EGF plays a dual role
      in the regulation of IAPs expression. On one hand, it increases cIAP-1 and cIAP-2
      basal expression and, on the other hand, it blocks the cleavage of cIAP-1 by
      caspases induced by TGF-beta.

PMID- 12044878
TI  - Identification of G protein-coupled receptor genes from the human genome
      sequence.
AB  - We have identified novel G protein-coupled receptors (GPCRs) with no introns in
      the coding region from the human genome sequence: 322 olfactory receptors; 22
      taste receptors; 128 registered GPCRs for endogenous ligands; 50 novel GPCR
      candidates homologous to registered GPCRs for endogenous ligands; and 59 novel
      GPCR candidates not homologous to registered GPCRs. The total number of GPCRs
      with and without introns in the human genome was estimated to be approximately
      950, of which 500 are odorant or taste receptors and 450 are receptors for
      endogenous ligands.

PMID- 12044879
TI  - The C-terminal domains of TACE weaken the inhibitory action of N-TIMP-3.
AB  - Tumor necrosis factor-alpha converting enzyme (TACE) is an ADAM (a disintegrin
      and metalloproteinases) that comprises an active catalytic domain and several C
      terminal domains. We compare the binding affinity and association rate constants
      of the N-terminal domain form of wild-type tissue inhibitor of metalloproteinase
      (TIMP-3; N-TIMP-3) and its mutants against full-length recombinant TACE and the
      truncated form of its catalytic domain. We show that the C-terminal domains of
      TACE substantially weaken the inhibitory action of N-TIMP-3. Further probing with
      hydroxamate inhibitors indicates that both forms of TACE have similar active site
      configurations. Our findings highlight the potential role of the C-terminal
      domains of ADAM proteinases in influencing TIMP interactions.

PMID- 12044880
TI  - Cdc48 can distinguish between native and non-native proteins in the absence of
      cofactors.
AB  - The ATPase Cdc48 is required for membrane fusion and protein degradation.
      Recently it has been suggested that Cdc48 in a complex with Ufd1 and Npl4 acts as
      an ubiquitin-dependent chaperone. Here it is shown that recombinant Cdc48 alone
      can distinguish between the native and the non-native conformation of model
      substrates. First, Cdc48 prevents luciferase from aggregating following a heat
      shock. Second, it inhibits the aggregation of rhodanese upon dilution. Third,
      Cdc48 binds specifically to heat-denatured luciferase. These chaperone-like
      functions seem to be independent of ATPase activity. Furthermore, Cdc48 can act
      as a co-chaperone in the Hsc70-Hsp40 chaperone system. These results show that
      Cdc48 possesses chaperone-like activities and can functionally interact with
      Hsc70. Cdc48's ability to recognise denatured proteins can also be a source of
      unspecific binding in biochemical interaction experiments.

PMID- 12044881
TI  - Implication of three isoforms of PLA(2) in human T-cell proliferation.
AB  - We observed that human (Jurkat) T-cells constitutively expressed the mRNA,
      encoding for the four isoforms of phospholipase A(2) (PLA(2)), i.e. two secretory
      (type IB and type V), and two cytosolic (type IV, Ca(2+)-dependent and type VI,
      Ca(2+)-independent). In order to assess whether these PLA(2) isoforms are active,
      we labeled Jurkat T-cells with [(3)H]arachidonic acid ([(3)H]AA) and determined
      its release into the extracellular medium in the presence of phorbol 12-myristate
      13-acetate (PMA) and ionomycin. The three PLA(2) isoforms seem functional as
      aristolochic acid and bromoenol lactone (BEL), the respective inhibitors of type
      IB/type V and type VI PLA(2)s, significantly inhibited the release of free
      [(3)H]AA. On the other hand, arachidonyl trifluoromethyl ketone (AACOCF(3)), an
      inhibitor of type IV PLA(2), failed to curtail significantly the release of free
      [(3)H]AA into the extracellular medium. We assessed the implication of these
      PLA(2) isoforms in transcription of the interleukin-2 (IL-2) gene, involved in T
      cell proliferation. Hence, aristolochic acid and BEL, but not AACOCF(3),
      significantly inhibited the PMA and ionomycin-induced induction of mRNA of IL-2.
      Similarly, aristolochic acid and BEL, but not AACOCF(3), significantly inhibited
      the PMA and ionomycin-induced secretion of IL-2 in the culture supernatants.
      Together these results suggest that human Jurkat T-cells possess two secretory
      and two cytosolic PLA(2) isoforms and only three of them (type IB, type V and
      type VI) are implicated in T-cell proliferation.

PMID- 12044882
TI  - Complex N-glycosylated form of nicastrin is stabilized and selectively bound to
      presenilin fragments.
AB  - The transmembrane glycoprotein nicastrin is a component of presenilin (PS)
      protein complex that is involved in gamma-cleavage of beta APP and site-3
      cleavage of Notch. PS undergoes endoproteolysis, and the proteolytic fragments
      are incorporated into the high molecular weight protein complexes that are highly
      stabilized. Here we show that Endo H-resistant, N-glycosylated form of nicastrin
      (p150-NCT) is highly stabilized and selectively bound to PS fragments. Moreover,
      loss-of-function mutations of nicastrin inhibited formation of fully glycosylated
      p150-NCT as well as stabilization of nicastrin, suggesting that glycosylation and
      stabilization of nicastrin polypeptides are tightly correlated with its function.

PMID- 12044884
TI  - A putative nuclear receptor coactivator (TMF/ARA160) associates with hbrm/hSNF2
      alpha and BRG-1/hSNF2 beta and localizes in the Golgi apparatus.
AB  - An ATP-dependent chromatin remodeling factor, SNF/SWI complex, acts as a
      coactivator for numerous transcriptional factors. One of the best-documented
      examples is nuclear receptors, although the molecular mechanism for this
      coactivation has not been sufficiently elucidated. Here we show that hbrm/hSNF2
      alpha and BRG-1/hSNF2 beta, the ATPase subunits of the human SNF/SWI complexes,
      specifically associate in vitro and in vivo with TATA element modulatory factor
      (TMF)/ARA160, which has been described as a binding protein to and coactivator
      for the androgen receptor. This interaction requires highly conserved N-terminal
      regions of hbrm/hSNF2 alpha and BRG-1/hSNF2 beta and a C-terminal region of
      TMF/ARA160. Immunofluorescence and Western blot studies revealed that the TMF
      isoforms differentially localize in the Golgi apparatus and the nucleus.

PMID- 12044883
TI  - Ascorbate inhibits iNOS expression in endotoxin- and IFN gamma-stimulated rat
      skeletal muscle endothelial cells.
AB  - Lipopolysaccharide endotoxin and interferon-gamma induced inducible nitric oxide
      synthase (iNOS) protein expression and nitrite/nitrate formation in microvascular
      endothelial cell cultures (ECs) derived from rat skeletal muscle. Pretreatment of
      ECs with ascorbate accumulated a large amount of ascorbate inside the cells and
      consequently decreased both intracellular oxidant level and iNOS induction. These
      effects of ascorbate were abolished in the presence of exogenous superoxide
      generated by xanthine oxidase/xanthine plus catalase but were not altered when N
      nitro-L-arginine methyl ester was applied to inhibit nitric oxide synthesis.
      Ascorbate also attenuated the activation of transcription factor IRF-1 but not NF
      kappa B. These results indicate that ascorbate inhibits iNOS expression in ECs by
      an antioxidant mechanism independent of both NF kappa B activation and the
      reported negative feedback effect of nitric oxide.

PMID- 12044885
TI  - Phospholipase C is required for glucose-induced calcium influx in budding yeast.
AB  - Intracellular calcium is a second messenger involved in several processes in
      yeast, such as mating, nutrient sensing, stress response and cell cycle events.
      It was reported that glucose addition stimulates a rapid increase in free calcium
      level in yeast. To investigate the calcium level variations induced by different
      stimuli we used a reporter system based on the photoprotein aequorin. Glucose
      addition (50 mM) to nutrient-starved cells induced an increase in free
      intracellular calcium concentration, mainly due to an influx from external
      medium. The increase of calcium reached its maximum 100-120 s after the stimulus.
      A concentration of about 20 mM glucose was required for a 50% increase in
      intracellular calcium. This response was completely abolished in strain plc1
      Delta and in the isogenic wild-type strain treated with 3-nitrocoumarin, a
      phosphatidylinositol-specific phospholipase C inhibitor, suggesting that Plc1p is
      essential for glucose-induced calcium increase. This suggests that Plc1p should
      have a significant role in transducing glucose signal. The calcium influx induced
      by addition of high glucose on cells previously stimulated with low glucose
      levels was inhibited in strains with a deletion in the GPR1 or GPA2 genes, which
      suggests that glucose would be detected through the Gpr1p/Gpa2p receptor/G
      protein-coupled (GPCR) complex. Moreover, the signal was completely abolished in
      a strain unable to phosphorylate glucose, which is consistent with the reported
      requirement of glucose phosphorylation for GPCR complex activation.

PMID- 12044886
TI  - The functional specificity of NeuroD is defined by a single amino acid residue
      (N11) in the basic domain.
AB  - In zebrafish, the basic helix-loop-helix (bHLH) gene neuroD specifies distinct
      neurons in the spinal cord. A preliminary experiment indicated that a related
      bHLH gene, ndr1a, normally expressed only in the olfactory organ in late embryos,
      also functions as neuroD to induce ectopic formation of spinal cord neurons in
      early embryos after introduction of its mRNA into early embryos. To define the
      functional specificity of these bHLH proteins, several mutant forms with selected
      point mutations in the basic domain were constructed and tested for inducing
      sensory neurons in the spinal cord. Our data indicate that the functional
      specificity of NeuroD to define sensory neurons is mainly due to a single residue
      (asparagine 11) in its basic domain.

PMID- 12044887
TI  - Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human
      keratinocytes: molecular mechanisms of action.
AB  - The effect of plant flavonoids on intercellular adhesion molecule-1 (ICAM-1)
      expression in human keratinocyte was investigated. ICAM-1 is known to mediate
      skin inflammation. Among the flavonoids tested, taxifolin was the most potent in
      inhibiting interferon gamma (IFN gamma)-induced ICAM-1 protein as well as mRNA
      expression in human keratinocytes. Much smaller dosages of taxifolin were
      required in primary keratinocytes compared to HaCaT (immortalized cell) to
      achieve similar levels of inhibition in the inducible ICAM-1 expression.
      Regulation of inducible ICAM-1 expression by taxifolin was at transcriptional
      level by inhibiting the activation of signal transducers and activators of
      transcription (STAT)1 and protein tyrosine phosphorylation of Janus kinase (JAK)1
      suggesting that the JAK-STAT pathway may be the molecular site of action of
      taxifolin. Finally, taxifolin pre-treatment also potently inhibited IFN gamma
      induced ICAM-1 expression in a reconstructed human skin equivalent suggesting
      therapeutic potential of taxifolin in skin pathological conditions related to
      increased cell adhesion and inflammation.

PMID- 12044888
TI  - Short-time non-enzymatic nitric oxide synthesis from L-arginine and hydrogen
      peroxide induced by shock waves treatment.
AB  - The evidence that nitric oxide (NO) production is possible by a non-enzymatic
      pathway has already been shown under restrictive experimental conditions. Here we
      show that NO can non-enzymatically be formed with short-time kinetics (min), by
      'bombing' with shock waves a solution containing 1 mM hydrogen peroxide and 10 mM
      L-arginine. This procedure is widening its medical application with surprisingly
      positive effects in tissue regeneration and our finding could be one of the first
      steps for the understanding of the biochemical responsible for these
      therapeutical effects.

PMID- 12044889
TI  - Development of photo-crosslinking reagents for protein kinase-substrate
      interactions.
AB  - The identification of relevant protein kinase-protein substrate partners remains
      a serious challenge on a genome-wide scale. The design and synthesis of a photo
      activatable nucleotide reagent to crosslink protein kinases with their substrates
      is described in which an azido group is appended to the gamma-phosphoryl and
      purine moieties of ATP. In the absence of UV, compounds of this class were shown
      to act as competitive inhibitors versus ATP and non-competitive inhibitors versus
      peptide substrate for the protein tyrosine kinase Csk, suggesting that they can
      form a ternary complex with kinase and protein substrate. In vitro experiments
      with protein kinases indicate the bifunctional reagent can induce covalent
      protein-protein crosslinking that is dependent on UV irradiation. That
      significant kinase-substrate crosslinking occurs is suggested by the fact that
      this crosslinking is competitively inhibited by ATP. The crosslinked adducts can
      be readily cleaved by phosphodiesterase which supports the model for crosslinking
      and provides a simple method to deconvolute the linked protein partners.

PMID- 12044890
TI  - Human small cell lung cancer NYH cells resistant to the bisdioxopiperazine ICRF
      187 exhibit a functional dominant Tyr165Ser mutation in the Walker A ATP binding
      site of topoisomerase II alpha.
AB  - Bisdioxopiperazine anti-cancer agents are catalytic inhibitors of topoisomerase
      II which by unknown means lock the enzyme in a closed clamp form and inhibit its
      ATPase activity. In order to demarcate a putative pharmacophore, we here describe
      a novel Tyr165Ser mutation in the enzyme's Walker A ATP binding site leading to
      specific bisdioxopiperazine resistance when transformed into a temperature
      conditional yeast system. The Tyr165Ser mutation differed from a previously
      described Arg162Gln by being heterozygous and by purified Tyr165Ser enzyme being
      drug-resistant in a kinetoplast DNA decatenation enzymatic assay. This suggested
      dominant nature of Tyr165Ser was supported by co-transformation studies in yeast
      of plasmids carrying wild type and mutant genes. These results enable a model of
      the bisdioxopiperazine pharmacophore using the proposed asymmetric ATP hydrolysis
      of the enzyme.

PMID- 12044891
TI  - Anti-neovascular therapy by liposomal DPP-CNDAC targeted to angiogenic vessels.
AB  - We previously reported that liposomalized 5'-O-dipalmitoylphosphatidyl 2'-C-cyano
      2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (DPP-CNDAC), a hydrophobized
      derivative of the novel antitumor nucleoside CNDAC, is quite useful for cancer
      therapy. On the other hand, for anti-neovascular therapy, we recently isolated
      peptides homing to angiogenic vessels from a phage-displayed random peptide
      library, and observed that peptide-modified liposomal adriamycin strongly
      suppressed tumor growth, perhaps through damaging angiogenic endothelial cells.
      In the present study, we modified DPP-CNDAC-liposomes with one of the angiogenic
      homing peptides, APRPG, and examined their antitumor activity. Three doses of
      APRPG-modified DPP-CNDAC-liposomes (15 mg/kg as CNDAC) strongly inhibited tumor
      growth compared with the same number of doses of unmodified DPP-CNDAC-liposomes.
      The life span was increased 31.8%, with one completely cured mouse out of the six
      mice treated. Since the accumulation of liposomes in the tumor tissue was not so
      much different between APRPG-liposomes and non-modified liposomes, the enhanced
      therapeutic efficacy may be explained as the alteration of targets, i.e. APRPG
      modified DPP-CNDAC-liposomes caused tumor growth suppression through damage of
      angiogenic endothelial cells. Anti-neovascular therapy promises no drug
      resistance, and should be effective against essentially any kind of solid tumor;
      and thus the present results demonstrate another benefit of the therapy, namely,
      high efficacy of cancer treatment.

PMID- 12044892
TI  - TGF-beta(1) and Smad4 overexpression induce a less invasive phenotype in highly
      invasive spindle carcinoma cells.
AB  - We have examined the effect of transforming growth factor beta(1) (TGF-beta(1))
      and overexpression of the Smad4 gene on the phenotype of Car C, a ras mutated
      highly malignant spindle carcinoma cell line. TGF-beta(1)-treated Car C cells
      overexpressing Smad4 spread with a flattened morphology with membrane ruffles
      abundant in vinculin and show a reduction in their invasive abilities. TGF
      beta(1) treatment and overexpression of Smad4 also enhanced the production of PAI
      1 measured by the activation of the p3TP-lux reporter gene containing a PAI-1
      related promoter. This activation was abolished with a dominant-negative Smad4
      construct. These results lead us to conclude that both TGF-beta(1) and Smad4
      overexpression reduce the invasive potential of Car C cells, probably via the
      Smad pathway.

PMID- 12044893
TI  - PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG
      CoA synthase and HMG-CoA reductase gene in THP-1 macrophages.
AB  - Recently it has been reported that macrophages express a nuclear receptor,
      peroxisome proliferator-activated receptor gamma (PPAR gamma). Using a ligand of
      PPAR gamma, troglitazone or pioglitazone, we have shown that the expression of
      two genes involved in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were increased by activation
      of PPAR gamma through a PPAR response element (PPRE) in THP-1 macrophages. In
      addition, treatment with troglitazone significantly increased the activity of HMG
      CoA reductase and the amount of intracellular cholesterol. Thus, we conclude that
      PPAR gamma and its agonists increase the cholesterol content of macrophages by
      the increased expression of genes involved in cholesterol biosynthesis. These
      findings suggest that PPAR gamma may play a role in cholesterol metabolism in
      macrophages.

PMID- 12044895
TI  - Evidence that BmTXK beta-BmKCT cDNA from Chinese scorpion Buthus martensii Karsch
      is an artifact generated in the reverse transcription process.

PMID- 12044894
TI  - Importance of platelets in VEGF-mediated angiogenesis in tumors.

PMID- 12044898
TI  - Glucosamine-6-phosphate synthase--the multi-facets enzyme.
AB  - L-Glutamine: D-fructose-6-phosphate amidotransferase, known under trivial name of
      glucosamine-6-phosphate synthase, as the only member of the amidotransferase
      subfamily of enzymes, does not display any ammonia-dependent activity. This
      enzyme, catalysing the first committed step in a pathway leading to the eventual
      formation of uridine 5'-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc), is an
      important point of metabolic control in biosynthesis of amino sugar-containing
      macromolecules. The molecular mechanism of reaction catalysed by GlcN-6-P
      synthase is complex and involves both amino transfer and sugar isomerisation.
      Substantial alterations to the enzyme structure and properties have been detected
      in different neoplastic tissues. GlcN-6-P synthase is inflicted in phenomenon of
      hexosamine-induced insulin resistance in diabetes. Finally, this enzyme has been
      proposed as a promising target in antifungal chemotherapy. Most of these issues,
      especially their molecular aspects, have been extensively studied in recent
      years. This article provides a comprehensive overview of the present knowledge on
      this multi-facets enzyme.

PMID- 12044899
TI  - Yeast cytochrome c peroxidase: mechanistic studies via protein engineering.
AB  - Cytochrome c peroxidase (CcP) is a yeast mitochondrial enzyme that catalyzes the
      reduction of hydrogen peroxide to water by ferrocytochrome c. It was the first
      heme enzyme to have its crystallographic structure determined and, as a
      consequence, has played a pivotal role in developing ideas about structural
      control of heme protein reactivity. Genetic engineering of the active site of
      CcP, along with structural, spectroscopic, and kinetic characterization of the
      mutant proteins has provided considerable insight into the mechanism of hydrogen
      peroxide activation, oxygen-oxygen bond cleavage, and formation of the higher
      oxidation state intermediates in heme enzymes. The catalytic mechanism involves
      complex formation between cytochrome c and CcP. The cytochrome c/CcP system has
      been very useful in elucidating the complexities of long-range electron transfer
      in biological systems, including protein-protein recognition, complex formation,
      and intracomplex electron transfer processes.

PMID- 12044900
TI  - High-molecular-weight protein hydrodynamics studied with a long-lifetime metal
      ligand complex.
AB  - [Ru(2,2'-bipyridine)(2)(4,4'-dicarboxy-2,2'-bipyridine)](2+) (RuBDc) is a very
      photostable probe that possesses favorable photophysical properties including
      long lifetime, high quantum yield, large Stokes' shift, and highly polarized
      emission. In the present study, we demonstrated the usefulness of this probe for
      monitoring the rotational diffusion of high-molecular-weight (MW) proteins. Using
      frequency-domain fluorometry with a high-intensity, blue light-emitting diode
      (LED) as the modulated light source, we compared the intensity and anisotropy
      decays of RuBDc conjugated to immunoglobulin G (IgG) and immunoglobulin M (IgM),
      which show a six-fold difference in MW We obtained slightly longer lifetimes for
      IgM (<tau>=428 ns in buffer) than IgG (<tau>=422 ns in buffer) in the absence and
      presence of glycerol, suggesting somewhat more efficient shielding of RuBDc from
      water in IgM than in IgG. The anisotropy decay data showed longer rotational
      correlation times for IgM (1623 and 65.7 ns in buffer) as compared to IgG (264
      and 42.5 ns in buffer). Importantly, the ratio of the long rotational correlation
      times of IgM to IgG in buffer was 6.2, which is very close to that of MW of IgM
      to IgG (6.0). The shorter correlation times are most likely to be associated with
      domain motions within the proteins. The anisotropy decays reflect both the
      molecular size and shape of the immunoglobulins, as well as the viscosity. These
      results show that RuBDc can have numerous applications in studies of high-MW
      protein hydrodynamics and in fluorescence polarization immunoassays (FPI) of high
      MW analytes.

PMID- 12044901
TI  - Butyrylcholinesterase-catalyzed hydrolysis of N-methylindoxyl acetate: analysis
      of volume changes upon reaction and hysteretic behavior.
AB  - Hydrolysis of the neutral substrate N-methylindoxyl acetate (NMIA) by wild-type
      human butyrylcholinesterase (BuChE) and peripheral site mutants (D70G, Y332A,
      D70G/Y332A) was found to follow the Michaelis-Menten kinetics. K(m) was 0.14 mM
      for wild-type, and 0.07-0.16 mM for D70G, Y332A and D70G/Y332A, indicating that
      the peripheral site is not involved in NMIA binding. The values of k(cat) were of
      the same order for all enzymes: 12,000-18,000 min(-1). Volume changes upon
      substrate binding (-DeltaV(K(m))) and the activation volumes (DeltaV++(k(cat))
      associated with hydrolysis of NMIA were calculated from the pressure dependence
      of the catalytic constants. Values of -DeltaV(K(m)) indicate that NMIA binds to
      an aromatic residue, presumed to be W82, the active site binding locus. Binding
      is accompanied by a release of water molecules from the gorge. Residue 70
      controls the number of water molecules that are released upon substrate binding.
      The values of DeltaV++(k(cat)), which are positive for wild-type and faintly
      positive for D70G, clearly indicate that the catalytic steps are accompanied by
      re-entry of water into the gorge. Results support the premise that residue D70 is
      involved in the conformational stabilization of the active site gorge and in
      control of its hydration. A slow transient, preceding the steady state, was seen
      on a time scale of several minutes. The induction time rapidly increased with
      NMIA concentration to reach a limit at substrate saturation. Much shorter
      induction times (<1 min) were seen for hydrolysis of benzoylcholine (BzCh) by
      wild-type BuChE and for hydrolysis of butyrylthiocholine (BuSCh) by the active
      site mutants E197Q and E197Q/G117H. This slow transient was interpreted in terms
      of hysteresis without kinetic cooperativity. The hysteretic behavior of BuChE
      results from a slow conformational equilibrium between two enzyme states E and
      E'. NMIA binds only to the primed form E'. Kosmotropic salts and hydrostatic
      pressure were found to shift the equilibrium toward E'. The E-->E' transition is
      accompanied by a negative activation volume (DeltaV++(0)= -45+/-10 ml/mol), and
      the E' form is more compact than E. Hydration water in the gorge of E' appears to
      be more structured than in the unprimed form.

PMID- 12044902
TI  - Structural basis for development of cathepsin B-specific noncovalent-type
      inhibitor: crystal structure of cathepsin B-E64c complex.
AB  - In order to elucidate the substrate specificity of the Sn subsites (n=1-3) of
      cathepsin B, its crystal structure inhibited by E64c [(+)-(2S,3S)-3-(1-[N-(3
      methylbutyl)amino]-leucylcarbonyl)oxirane-2-carboxylic acid] was analyzed by the
      X-ray diffraction method. Iterative manual rebuilding and convenient conjugate
      refinement of structure decreased R- and free R-factors to 19.7% and to 23.9%,
      respectively, where 130 water molecules were included for the refinement using
      14,759 independent reflections from 10 to 2.3 A resolution. The epoxy carbonyl
      carbon of E64c was covalently bonded to the Cys(29) S(gamma) atom and the
      remaining parts were located at Sn subsites (n=1-3). The substrate specificity of
      these subsites was characterized based on their interactions with the inhibitor.
      Base on these structural data, we developed a novel cathepsin B-specific
      noncovalent-type inhibitor, which may bind to S2'-S3. The molecular design of
      possessing structural elements of both CA074 and E64c, assisted by energy
      minimization and molecular dynamics (MD) simulation, may lead to a new lead
      noncovalent-type inhibitor.

PMID- 12044903
TI  - MALDI-TOF mass spectrometry characterization of recombinant hydrophobic mutants
      containing the GCN4 basic region/leucine zipper motif.
AB  - We used matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) to characterize hydrophobic, alanine-rich mutants of
      the basic region/leucine zipper (bZIP) protein GCN4. These bacterially expressed
      proteins were generated to probe how small, alpha-helical proteins bind specific
      DNA sites. Enzymatic digestion mapping combined with MALDI-TOF MS
      characterization of protein fragments allowed us to resolve mass discrepancies
      between the expected and observed molecular mass measurements. Changes in mass
      were attributed to posttranslational modifications (PTMs) by proteolytic cleavage
      of the initiating methionine residue, carbamylation at the amino terminus,
      oxidation of histidine side chains, and oxidative addition of beta
      mercaptoethanol (BME) at the cysteine side chain. Proteins can undergo a wide
      variety of co-translational modifications and PTMs during growth, isolation, and
      purification. Such changes in mass can only be detected by a high-resolution
      technique such as MALDI, which in conjunction with enzymatic digestion mapping,
      becomes a powerful methodology for characterization of protein structure.

PMID- 12044904
TI  - Role of arginine 292 in the catalytic activity of chondroitin AC lyase from
      Flavobacterium heparinum.
AB  - Chondroitin AC lyase (chondroitinase EC 4.2.2.5), an eliminase from
      Flavobacterium heparinum, cleaves chondroitin sulfate glycosaminoglycans (GAGs)
      at 1,4 glycosidic linkages between N-acetylgalactosamine and glucuronic acid
      residues. Cleavage occurs through beta-elimination in a random endolytic action
      pattern. Crystal structures of chondroitin AC lyase (wild type) complexed with
      oligosaccharides reveal a binding site within a narrow and shallow protein
      channel, suggesting several amino acids as candidates for the active site
      residues. Site-specific mutagenesis studies on residues within the active-site
      tunnel revealed that only the Arg to Ala 292 mutation (R292A) retained activity.
      Furthermore, structural data suggested that R292 was primarily involved in
      recognition of N-acetyl or O-sulfo moieties of galactosamine residues and did not
      directly participate in catalysis. The current study demonstrates that the R292A
      mutation affords approximately 10-fold higher K(m) values but no significant
      change in V(max), consistent with hypothesis that R292 is involved in binding the
      O-sulfo moiety of the saccharide residues. Change in chondroitin sulfate
      viscosity, as a function of its enzymatic cleavage, affords a shallower concave
      curve for the R292A mutant, suggesting its action pattern is neither purely
      random endolytic nor purely random exolytic. Product studies using gel
      electrophoresis confirm the altered action pattern of this mutant. Thus, these
      data suggest that the R292A mutation effectively reduces binding affinity, making
      it possible for the oligosaccharide chain, still bound after initial endolytic
      cleavage, to slide through the tunnel to the catalytic site for subsequent,
      processive, step-wise, exolytic cleavage.

PMID- 12044905
TI  - Improved practical usefulness of firefly luciferase by gene chimerization and
      random mutagenesis.
AB  - To improve the practical usefulness of the firefly luciferase, we performed gene
      chimerization between Photinus pyralis luciferase and a thermostable variant of
      Luciola cruciata luciferase. One chimeric luciferase showed low K(m) value for
      substrate ATP and similar stability to thermostable L. cruciata luciferase. We
      then introduced random mutations in the corresponding gene and screened for
      increased catalytic efficiency. Amino acid replacement of Thr219, Val239 and
      Val290 affected the kinetic parameters. Therefore, we combined these three
      mutations. One mutant, ABcT219I,V239I, showed high catalytic efficiency
      comparable to P. pyralis luciferase and high stability similar to thermostable L.
      cruciata luciferase. The pH-dependence of the bioluminescence emission spectra
      was also examined. In contrast to wild-type firefly luciferases characterized to
      date, the mutant did not show the pH-dependent red spectrum shift.

PMID- 12044906
TI  - Reductive unfolding and oxidative refolding of a Bowman-Birk inhibitor from
      horsegram seeds (Dolichos biflorus): evidence for "hyperreactive" disulfide bonds
      and rate-limiting nature of disulfide isomerization in folding.
AB  - Horsegram protease inhibitor belongs to the Bowman-Birk class (BBIs) of low
      molecular weight (8-10 kDa), disulfide-rich, "dual" inhibitors, which can bind
      and inhibit trypsin and chymotrypsin either independently or simultaneously. They
      have seven conserved disulfide bonds. Horsegram BBI exhibits remarkable stability
      against denaturants like urea, guanidine hydrochloride (GdmCl) and heat, which
      can be attributed to these conserved disulfide bonds. On reductive denaturation,
      horsegram BBI follows the "two-state" mode of unfolding where all the disulfide
      bonds are reduced simultaneously resulting in the fully reduced protein without
      any accumulation of partially reduced intermediates. Reduction with
      dithiothreitol (DTT) followed apparent first-order kinetics and the rate
      constants (k(r)) indicated that the disulfide bonds were "hyperreactive" in
      nature. Oxidative refolding of the fully reduced and denatured inhibitor was
      possible at very low protein concentration in the presence of "redox" combination
      of reduced and oxidized glutathiones. Simultaneous recovery of trypsin and
      chymotryptic inhibitory activities indicated the concomitant folding of both the
      inhibitory subdomains. Folding efficiency decreased in the absence of the
      glutathiones and in the presence of denaturants (6 M urea and 4 M GdmCl),
      indicating the importance of disulfide shuffling and the formation of noncovalent
      interactions and secondary structural elements, respectively, for folding
      efficiency. Folding rate was significantly improved in the presence of protein
      disulfide isomerase (PDI). A 3-fold enhancement of rate was observed in the
      presence of PDI at molar ratio of 1:20 (PDI/inhibitor), indicating that disulfide
      bond formation and isomerization to be rate limiting in folding. Peptide prolyl
      cis-trans isomerase (PPI) did not affect rate at low concentrations, but at molar
      ratios of 1:1.5 (PPI/inhibitor), there was 1.4-fold enhancement of the folding
      rate, indicating that the prolyl imidic bond isomerizations may be slowing down
      the folding reaction but were not rate limiting.

PMID- 12044907
TI  - pH, inhibitor, and substrate specificity studies on Escherichia coli penicillin
      binding protein 5.
AB  - The recent structural determination of Escherichia coli penicillin-binding
      protein 5 (PBP 5) provides the opportunity for detailed structure-function
      studies of this enzyme. PBP 5 was investigated in terms of its stability, linear
      reaction kinetics, acyl-donor substrate specificity, inhibition by a number of
      active site-directed reagents, and pH profile. PBP 5 demonstrated linear reaction
      kinetics for up to several hours. Dilution of PBP 5 generally resulted in
      substantial loss of activity, unless BSA or a BSA derivative was added to the
      diluting buffer. PBP 5 did not demonstrate a significant preference against a
      simple set of five alpha- and epsilon-substituted L-Lys-D-Ala-D-Ala derivatives,
      suggesting that PBP 5 lacks specificity for the cross-linked state of cell wall
      substrates. Among a number of active site-directed reagents, only some thiol
      directed reagents gave substantial inhibition. Notably, serine-directed reagents,
      organic phosphates, and simple boronic acids were ineffective as inhibitors. PBP
      5 was stable over the pH range 4.6-12.3, and the k(cat)/K(m) vs. pH profile for
      activity against Ac(2)-L-Lys-D-Ala-D-Ala was bell-shaped, with pK(a)s at 8.2 and
      11.1. This is the first complete pH profile, including both acidic and basic
      limbs, for a PBP-catalyzed DD-carboxypeptidase (CPase) reaction. Based on its
      structure, similarity to Class A beta-lactamases, and results from mutagenesis
      studies, the acidic and basic limbs of the pH profile of PBP 5 are assigned to
      Lys-47 and Lys-213, respectively. This assignment supports a role for Lys-47 as
      the general base for acylation and deacylation reactions.

PMID- 12044908
TI  - The role of beta-strand 5A of plasminogen activator inhibitor-1 in regulation of
      its latency transition and inhibitory activity by vitronectin.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti
      thrombotic and anti-cancer therapy. It circulates in plasma in a complex with
      vitronectin (VN). We have studied biochemical mechanisms for PAI-1 neutralisation
      and its modulation by VN, using site-directed mutagenesis and limited
      proteolysis. We demonstrate that VN, besides delaying conversion of PAI-1 to the
      inactive latent form, also protects PAI-1 against cold- and detergent-induced
      substrate behaviour and counteracts conversion of PAI-1 to inert forms by certain
      amphipathic organochemical compounds. VN protection against cold- and detergent
      induced substrate behaviour is associated with inhibition of the proteolytic
      susceptibility of beta-strand 5A. Alanine substitution of a lysine residue placed
      centrally in beta-strand 5A implied a VN-induced acceleration of latency
      transition, instead of the normal delay. This substitution not only protects PAI
      1 against neutralisation, but also counteracts VN-induced protection against
      neutralisation. We conclude that beta-strand 5A plays a crucial role in VN
      regulation of PAI-1 activity.

PMID- 12044909
TI  - Cloning, expression and mutagenesis of a subunit contact of rabbit muscle
      specific (betabeta) enolase.
AB  - The cDNA for rabbit muscle-specific (betabeta) enolase was cloned, sequenced and
      expressed in Escherichia coli. This betabeta-enolase differs at eight positions
      from that sequenced by Chin (17). Site-directed mutagenesis was used to change
      residue 414 from glutamate to leucine, thereby abolishing a salt bridge involved
      in subunit contacts. Recombinant wild-type and mutant enolase were purified from
      E. coli and compared to enolase isolated from rabbit muscle. Molecular weights
      were determined by mass spectrometry. All three betabeta-enolases had similar
      kinetics, and UV and circular dichroism (CD) spectra. The mutant enolase was far
      more sensitive to inactivation by pressure, by KCl or EDTA, and by sodium
      perchlorate. We confirmed, by analytical ultracentrifugation, that the sodium
      perchlorate inactivation was due to dissociation. DeltaG(o) for dissociation of
      enolase was decreased from 49.7 kJ/mol for the wild-type enzyme to 42.3 kJ/mol
      for the mutant. In contrast to the wild-type enzyme, perchlorate inactivation of
      E414L was accompanied by a small loss of secondary structure.

PMID- 12044910
TI  - Purine nucleoside phosphorylase from Cellulomonas sp.: physicochemical properties
      and binding of substrates determined by ligand-dependent enhancement of enzyme
      intrinsic fluorescence, and by protective effects of ligands on thermal
      inactivation of the enzyme.
AB  - Purine nucleoside phosphorylase (PNP) from Cellulomonas sp., homotrimeric in the
      crystalline state, is also a trimer in solution. Other features of the enzyme are
      typical for "low molecular mass" PNPs, except for its unusual stability at pH 11.
      Purine bases, alpha-D-ribose-1-phosphate (R1P) and phosphate enhance the
      intrinsic fluorescence of Cellulomonas PNP, and hence form binary complexes and
      induce conformational changes of the protein that alter the microenvironment of
      tryptophan residue(s). The effect due to guanine (Gua) binding is much higher
      than those caused by other ligands, suggesting that the enzyme preferentially
      binds a fluorescent, most probably rare tautomeric anionic form of Gua, further
      shown by comparison of emission properties of the PNP/Gua complex with that of
      Gua anion and its N-methyl derivatives. Guanosine (Guo) and inosine (Ino) at 100
      microM concentration show little and no effect, respectively, on enzyme intrinsic
      fluorescence, but their protective effect against thermal inactivation of the
      enzyme points to their forming weak binary complexes with PNP. Binding of Gua,
      hypoxanthine (Hx) and R1P to the trimeric enzyme is described by one dissociation
      constant, K(d)=0.46 microM for Gua, 3.0 microM for Hx, and 60 microM for R1P. The
      binding stoichiometry for Gua (and probably Hx) is three ligand molecules per
      enzyme trimer. Effects of phosphate on the enzyme intrinsic fluorescence are due
      not only to binding, but also to an increase in ionic strength, as shown by
      titration with KCl. When corrected for effects of ionic strength, titration data
      with phosphate are most consistent with one dissociation constant, K(d)=270
      microM, but existence of a very weak binding site with K(d)>50 mM could not be
      unequivocally ruled out. Binding of Gua to the PNP/phosphate binary complex is
      weaker (K(d)=1.7 microM) than to the free enzyme (K(d)=0.46 microM), suggesting
      that phosphate helps release the purine base in the catalytic process of
      phosphorolysis. The results indicate that nonlinear kinetic plots of initial
      velocity, typical for PNPs, including Cellulomonas PNP, are not, as generally
      assumed, due to cooperative interaction between monomers forming the trimer, but
      to a more complex kinetic mechanism than hitherto considered.

PMID- 12044911
TI  - Arylamidase activity of neutral proteinase from Saccharomonospora canescens.
      Comparison with other Zn-proteinases that exhibit the same activity.
AB  - The arylamidase activity of Zn-proteinase from Saccharomonospora canescens (NPS)
      was studied with series of peptide nitroanilides of varying amino acid sequence
      and N-acyl blocking groups. The partial mapping of the enzyme S(1), S(2), S(3),
      S(4) subsites shows that variations in all positions P(1) to P(4) in the
      substrate structure affect the catalytic efficiency. The importance of P(4)-S(4)
      and P(1)-S(1) interactions, which is a characteristic feature of the serine
      proteinases, is evidenced for the studied Zn-proteinases NPS and serralysin too.
      The presence of arylamidase activity in the case of Zn-proteinases-astacin EC
      3.4.24.21 and serralysin EC 3.4.24.40 is correlated with some specific
      characteristics of their active site structure: penta-coordinated Zn(2+) and a
      tyrosyl residue as a fifth ligand to the Zn(2+). It is assumed that this tyrosyl
      residue plays a role in the productive binding and stabilization of the
      tetrahedral adduct formed during the reaction of enzyme-catalysed hydrolysis of
      peptide arylamides of corresponding length and sequence.

PMID- 12044912
TI  - Origins of follicular cells and ontogeny of steroidogenesis in ovine fetal
      ovaries.
AB  - Using fetal sheep as the experimental model, we have elucidated some of the key
      events that culminate in the formation of primordial follicles. A special effort
      was made to determine the source of the somatic cells that ultimately become
      granulosa cells of primordial follicles. Between gestational days 38-100: (1)
      light and electron microscopy was used to characterize changes in ovarian
      histoarchitecture; (2) incorporation of BrdU was used to identify populations of
      proliferating cells within fetal ovaries before, during and after, follicular
      formation; and (3) in situ hybridisation was used to determine the cell-specific
      and temporal patterns of expression of mRNAs encoding for selected steroidogenic
      enzymes. At day 38 somatic (pregranulosa) cells were in contact with oogonia and
      easily distinguished from endothelial and mesenchymal cells. Between days 38 and
      45, pregranulosa cell-oogonia complexes progressively coalesced to form 'tube
      like' structures referred to as ovigerous cords. These cords consisted of
      pregranulosa cells and oogonia arranged such that pregranulosa cells formed the
      outer wall of the cords. Ovigerous cords were avascular, enveloped in a prominent
      basal lamina, open-ended where they interfaced with the ovarian surface
      epithelium, and formed a separate compartment whereby oogonia/oocytes were
      segregated from the surrounding stroma and vasculature until the time of
      follicular formation. The structural integrity of ovigerous cords was maintained
      through day 75, at which time primordial follicles (type 1 and type 1a) first
      emerged from the cords at the interface of the cortex and medulla. On the basis
      of the sequential structural changes that occurred during the differentiation and
      development of fetal ovaries and location of proliferating cells identified by
      the incorporation of BrdU, we conclude that the majority of the granulosa cells
      in primordial follicles are derived from mesothelial cells originating from the
      ovarian surface epithelium. In addition, from the cell-specific distribution and
      temporal pattern of expression of mRNAs for key steroidogenic enzymes we
      hypothesize that steroid hormones may play a pivotal paracrine/autocrine role in
      the formation and/or function of ovigerous cords as well as the development of
      the ovarian vascular network.

PMID- 12044913
TI  - Using expressed sequence tag databases to identify ovarian genes of interest.
AB  - GenBank contains 4879 expressed sequence tags (EST) derived from four non
      normalized human ovarian cDNA libraries. Of these EST, 2646 are contributors to
      UniGene clusters and have UniGene numbers. The EST map to 1206 distinct UniGenes.
      A gene expression profile was established for the human ovary by identifying the
      abundance of each UniGene cluster and its corresponding annotation. The most
      highly expressed transcripts were for proteins associated with protein synthesis
      (ribosomal proteins, elongation factors, thymosins, etc.). However, there are
      also transcripts for genes of unknown function that are ovary-specific. This
      ovarian gene expression profile provides useful data for the design of DNA
      microarrays targeted at ovarian function and highlights novel sequences that
      warrant further investigation.

PMID- 12044914
TI  - Bmp15 mutations and ovarian function.
AB  - BMP15, also known as growth and differentiation factor 9B (GDF9B), is a member of
      the transforming growth factor beta superfamily (TGFbeta) which in humans,
      rodents and sheep is expressed exclusively in the oocyte. BMP15 is closely
      related to GDF9, another oocyte-specific member of this superfamily which has
      been shown to be essential for early ovarian folliculogenesis. Inactivation of
      the BMP15 gene in mice has shown only minor effects on fertility. However,
      Inverdale and Hanna lines of sheep carry naturally occurring mutations in BMP15
      which highlight differences in the action of this gene between mice and other
      mammals. Sheep which are heterozygous show an increase in ovulation rate whereas
      homozygotes are infertile. The granulosa cell receptor which mediates the BMP15
      response has not yet been identified, but the discovery that a point mutation in
      the BMP1B receptor in Booroola sheep is responsible for increased ovulation rate
      highlights the importance of the TGFbeta signalling molecules in early
      folliculogenesis.

PMID- 12044915
TI  - Clinical disorders associated with abnormal cholesterol transport: mutations in
      the steroidogenic acute regulatory protein.
AB  - The transport of cholesterol to the inner mitochondrial membrane of steroidogenic
      cells constitutes the rate-limiting step in trophic hormone regulated steroid
      biosynthesis and requires de novo protein synthesis. Several years ago a
      candidate regulator protein was purified and its cDNA cloned from MA-10 mouse
      Leydig tumor cells. Expression of this protein resulted in an increase in
      steroidogenesis in unstimulated cells and it was named the Steroidogenic Acute
      Regulatory protein or StAR. Mutations in the StAR gene were found to be the cause
      of the potentially lethal disease in humans known as congenital lipoid adrenal
      hyperplasia (lipoid CAH), a condition characterized by an almost complete
      inability of the newborn to synthesize steroids. The defect in steroid synthesis
      in lipoid CAH is caused by the failure of affected individuals to transport
      cholesterol to the inner mitochondria membrane, thus proving the essential role
      of StAR in cholesterol transport. StAR null mice display a phenotype that is
      essentially identical to the human condition. In summary, both naturally
      occurring disorders in humans and genetic manipulation in mice have demonstrated
      that the StAR protein is an absolute requirement in the rate-limiting step in
      steroidogenesis, the transfer of cholesterol into the mitochondria.

PMID- 12044916
TI  - Ovarian steroid receptors and their role in ovarian function.
AB  - The steroidogenic pathway within the ovary gives rise to progestins, androgens
      and oestrogens, all of which act via specific nuclear receptors to regulate
      reproductive function and maintain fertility. The precise role of oestrogen in
      the ovary remains to be elucidated, hence the data presented here which arises
      from studies designed to resolve this issue. Oestrogens signal via two receptor
      subtypes ERalpha and ERbeta, both of which are present in the ovary. ERbeta, the
      most abundant mRNA, is primarily expressed by GC where it transduces signals from
      ovarian-derived and exogenous oestrogens. Specific roles for each of the ERs in
      the ovary have yet to be established, despite ER knockout studies indicating both
      are required for normal function. The ArKO mouse is a model of oestrogen
      insufficiency. These mice are infertile as a result of arrested folliculogenesis
      (at the antral stage) and a failure to ovulate. Trans/re-differentiation of
      somatic cells in the ovary gives rise to Sertoli cell-like and Leydig cell-like
      cells within abnormal follicular structures. Disruption to the balance of sex
      steroids in the ovary is likely to facilitate this phenotype. Future studies will
      focus on the regulation of somatic cell differentiation, assigning roles to
      individual ERs and establishing definitive targets of oestrogen action in the
      ovary.

PMID- 12044917
TI  - Recruitment and development of the follicle; the roles of the transforming growth
      factor-beta superfamily.
AB  - Peripheral endocrine hormones and local paracrine and autocrine factors
      contribute, in a coordinated fashion, to the processes of recruitment,
      development or atresia, selection and ovulation of follicles. Among the local
      ovarian factors, there is growing evidence from genetic and experimental data
      that many members of the transforming growth factor (TGFbeta) superfamily have a
      biological role to play in folliculogenesis. These members include activin,
      inhibin, TGFbeta, BMP, GDF9 and perhaps MIS. In this review, we discuss the
      potential roles of the TGFbeta superfamily members, in particular activin, during
      folliculogenesis. Since the actions of these factors are determined by ligand
      availability, receptor expression and modulation of their signal transduction
      pathways, we also collate information on the expression of their signalling
      components in the follicle. We conclude that the TGFbeta superfamily signalling
      pathways, in particular activin's pathway, reside in the ovary. Furthermore,
      follistatin and beta-glycan-components of the accessory binding protein system
      that modifies activin action-are also present in follicles. In the post-natal rat
      ovary, the changes in receptor/Smad expression coincide with granulosa cell
      proliferation and antrum formation. We hypothesise that these pathway components
      are expressed in a temporal and cell-specific manner to meet the changing demands
      of cells during follicular development. The analysis of the components of the
      signal transduction pathways of the TGFbeta family members in populations of
      defined follicles and the identification of activated pathways in individually
      stimulated follicles should help clarify the roles of the TGFbeta members in
      folliculogenesis.

PMID- 12044918
TI  - Ovarian tissue remodeling: role of matrix metalloproteinases and their
      inhibitors.
AB  - Follicular formation, growth or atresia, and ovulation as well as luteal
      formation and subsequent regression are dependent upon cyclical remodeling of the
      extracellular matrix (ECM). The proteinaceous and nonproteinaceous components of
      the ECM provide the tissue specific, extracellular architecture to which cells
      attach. Furthermore, the ECM modulates cellular activities through cellular
      surface receptors and serves as a reservoir for specific growth factors,
      cytokines, and binding proteins. The ability of the ECM to direct the
      proliferation, differentiation and function of cells implicates ECM remodeling in
      normal ovarian function. Specific components of the ECM are cleaved by matrix
      metalloproteinases (MMPs) whose activities are specifically inhibited by tissue
      inhibitors of metalloproteinases (TIMPs). MMPs are zinc- and calcium-dependent
      enzymes that collectively degrade proteinaceous components of the ECM. Controlled
      turnover of ECM by MMPs and TIMPs may be essential for creating and (or)
      preserving microenvironments conducive to follicular and luteal function and is
      likely dependent upon the ratio of enzyme to inhibitor. To date, most studies
      have focused upon correlating ovarian expression of MMPs and TIMPs with various
      stages of the reproductive cycle. From these studies, many potential key
      regulators of ovarian ECM remodeling have been identified. This review presents
      evidence for the involvement of MMPs and TIMPs in ECM remodeling associated with
      follicular and luteal function.

PMID- 12044919
TI  - Extracellular matrix of the bovine ovarian membrana granulosa.
AB  - Much is known about the control of the development of ovarian follicles by growth
      factors and hormones. The study of extracellular matrix in the ovary, though, is
      a relatively new area. To date much research has focused on identifying the
      matrix components present, and more recently, its production and the
      physiological roles. In this review we focus on the changes that occur in the
      follicular basal lamina from primordial follicles through to ovulation and
      formation of the corpus luteum, the changes that occur during follicular atresia,
      and we discuss our observations of a novel matrix which forms in the membrana
      granulosa. The follicular basal lamina changes considerably during follicular
      development in its expression pattern of type IV collagens. Of the laminin chains
      examined, there appears only to be an increase in amount, except for laminin
      alpha2. It is expressed only in a small proportion of healthy antral follicles
      and in the majority of atretic antral follicles. Call-Exner bodies have the same
      composition as the basal lamina, except they do not contain laminin alpha2, even
      when the follicular basal lamina does. The novel matrix that develops within the
      membrana granulosa is similar in composition to Call-Exner bodies which occur
      predominantly in preantral follicles, except that it is far more common in large
      antral follicles, does not induce polarization of the surrounding granulosa
      cells, and does not contain follicular fluid-like material as the Call-Exner
      bodies of some species do. The expression of this matrix occurs prior to and
      during the time when granulosa cells express steroidogenic enzymes. It does not
      exist in corpora lutea. In addition large luteal cells, derived from granulosa
      cells, do not appear to have a basal lamina. These findings suggest that the
      maturational changes in the membrana granulosa are accompanied by changes in the
      matrix.

PMID- 12044920
TI  - Regulation of progesterone and prostaglandin F2alpha production in the CL.
AB  - After the luteinizing hormone (LH) surge, the cells that remain from the ovulated
      follicle undergo a process of differentiation termed luteinization. Two key
      features of the cells after luteinization are the capacity for tremendous
      production of progesterone [10(16) molecules of progesterone per (min/(g of CL))]
      and the capacity to undergo regression or death of the cells at the appropriate
      time. There are two steroidogenic cell types, the small and large luteal cells
      that are regulated by different mechanisms. In small luteal cells, production of
      progesterone is stimulated by LH through the protein kinase A (PKA) pathway. The
      large luteal cells of ruminants produce large quantities of progesterone that is
      independent of LH stimulation. Although luteotrophins clearly regulate luteal
      function, much of luteal progesterone production in some species appears to be
      constitutive, consistent with the autonomous aspects of the large luteal cell.
      The key regulated step in luteal progesterone production appears to be regulation
      of transport of cholesterol to the inner mitochondrial membrane apparently
      mediated by the steroidogenic acute regulatory protein (StAR). In addition, our
      recent research indicates that PKA is tonically active in large luteal cells and
      this may be responsible for the high, relatively autonomous nature of luteal
      progesterone production. Regression of the corpus luteum (CL) in many species is
      initiated by prostaglandin (PG) F2alpha secreted from the uterus. Luteal cells
      also have the capacity for production of PGF2alpha. Luteal PGF2alpha production
      can be regulated by a variety of substances including inhibition by progesterone
      and stimulation by cytokines. We have also characterized a positive feedback
      pathway in ruminant and porcine CL in which small amounts of uterine PGF(2alpha)
      stimulate intraluteal production of PGF2alpha due to induction of the
      cycloxygenase-2 (Cox-2) enzyme in large luteal cells. This positive feedback
      pathway is only present in CL that has acquired the capacity for luteal
      regression ( approximately day 7 in cow, approximately day 13 in pig). Regulation
      by protein kinase C (PKC) of transcriptional factors interacting with an E-box in
      the 5' flanking region of the Cox-2 gene is the critical regulatory element
      involved in this positive feedback pathway. Thus, luteinization in some species
      appears to change specific gene transcription such that progesterone production
      becomes relatively independent of acute luteotrophic regulation and intraluteal
      PGF2alpha synthesis is induced by the second messenger pathways that are
      activated by PGF2alpha.

PMID- 12044921
TI  - The corpus luteum and interstitial tissue in a marsupial, the brushtail possum
      (Trichosurus vulpecula).
AB  - The Australian brushtail possum (Trichosurus vulpecula) is a nocturnal, arboreal
      marsupial. It has become a pest of significant ecological and economic importance
      in New Zealand, and thus a renewed interest in understanding the reproductive
      biology of this species has been generated. The corpus luteum (CL) in possums is
      a largely autonomous gland in that it does not rely on pituitary hormones to
      function and is not responsive to luteolytic agents for its demise. Its
      importance in regulating the oestrous cycle and pregnancy has been established;
      however, little is known regarding the mechanisms involved in its function.
      Interstitial tissue (IT) is a prominent feature found throughout the ovarian
      stroma, yet little is known regarding the origin or function of these cells.
      Based on histological examinations, our data support the hypothesis that
      interstitial tissue arises from a unique cell type called medullary cords during
      early ovarian development. Using possum-specific probes for proteins involved in
      steroidogenesis, receptors for pituitary hormones and members of the TGF-beta
      superfamily we have initiated studies investigating the expression of genes that
      may be important in the function and regulation of the CL and interstitial
      tissue. Results show that both tissues are steroidogenic and that both express
      receptors for prolactin and luteinising hormone (LH). Collectively these findings
      suggest that prolactin and LH may be important in the regulation of
      steroidogenesis in the CL and interstitial tissue in possums.

PMID- 12044922
TI  - Molecular pathogenesis of granulosa cell tumours.
AB  - Granulosa cell tumours (GCT) of the ovary arise from granulosa cells of the ovary
      on morphological, biochemical and molecular criteria. In order to understand the
      molecular pathogenesis of these tumours better we have sought to define their
      molecular phenotype, to identify activating mutations of the FSH-signalling
      pathway, to characterise their estrogen receptor expression and to explore the
      hypothesis that GCT may be resistant to inhibin. The pattern of gene expression
      observed in GCT suggests a phenotype which is similar to that of late
      preovulatory granulosa cells which would be consistent with activation of the FSH
      receptor signalling pathway, however, there is no evidence for activating
      mutations of either the FSH receptor or the associated trimeric G-proteins.
      Estrogen receptor beta is abundantly expressed in GCT. The various subunits and
      isoforms of the activin-inhibin receptor are expressed in GCT. These observations
      provide a basis for future studies of GCT, including further characterisation of
      signalling pathways known to be important in the regulation of granulosa cell
      growth and differentiation.

PMID- 12044924
TI  - Changes in the mouse ovarian surface epithelium with age and ovulation number.
AB  - The cell biology of ovarian surface epithelium (OSE) was studied in mice of
      varying age and lifetime total ovulation number (OV#), to determine the relative
      importance of these factors in control of OSE proliferation and development of
      invaginations and cysts. Ovaries from Swiss Webster mice (total OV# median: range
      [n mice]) were collected at 4 weeks of age (prepubertal; 0[9]), from 3-month
      virgins (113: 11-235 [55]), from 12-month old breeders (217: 97-386 [21]) and
      from 8-month virgin mice, housed in split cages alongside a male, to induce
      continuous oestrous cycles (629: 456-908 [16]). Scanning electron microscopy
      revealed cuboidal and squamous cells in OSE from all ages. Higher total OV#
      markedly increased the rate of OSE invagination and layering. Histology showed
      the incidence of cysts, which had the appearance of benign serous cystadenomata,
      increased with age rather than total OV#.

PMID- 12044923
TI  - Inhibins/activins as diagnostic markers for ovarian cancer.
AB  - It is widely recognised that the early detection and subsequent assessment of
      recurrence of ovarian cancers are key steps for successful treatment. Available
      serum markers (e.g. CA125) are sensitive for some epithelial carcinomas (e.g.
      serous, endometrioid, clear cell), however, these markers are less sensitive for
      granulosa cell tumours and mucinous carcinomas. Serum inhibin is an ovarian
      product which decreases to non detectable levels after menopause, however,
      certain ovarian cancers (mucinous carcinomas and sex cord stromal tumours such as
      granulosa cell tumours) continue to produce inhibin which provides a basis for a
      serum diagnostic test. Studies from this and other laboratories have investigated
      the suitability of inhibin as a diagnostic marker by identifying which inhibin
      (inhibin A (alphabetaA), inhibin B (alphabetaB), free alpha subunit) or activin
      (betaAbetaA) form is associated with these cancers. Available data show that
      inhibin assays which detect all inhibin forms, i.e. assays which detect the alpha
      subunit both as the free form and as an alphabeta subunit dimer provide the
      highest sensitivity/specificity characteristics as an ovarian cancer diagnostic
      test. This review will discuss the data supporting these observations and show
      recent studies in which a new alpha subunit monoclonal antibody-based ELISA is
      used as a potential diagnostic test. Furthermore, based on the high
      sensitivity/specificity characteristics of the respective assays for the various
      types of ovarian cancer, the combination of the inhibin assay with CA125 detects
      the majority of all ovarian cancers.

PMID- 12044925
TI  - Hyperandrogenaemia and the ovary.
AB  - Hyperandrogenaemia in women presents in a variety of ways, including problems
      with the reproductive system. The commonest cause is polycystic ovary syndrome
      (PCOS), a condition found in 5-10% of all women. PCOS has origins that are
      genetic and environmental but the end organ, the ovary, exhibits excessive
      androgen production with enhanced sensitivity to luteinising hormone and insulin.
      Interventions include approaches that target both these hormones as well as the
      ovary itself.

PMID- 12044926
TI  - DNA microarrays for assessing ovarian cancer gene expression.
AB  - Although DNA microarray analysis is presented as a revolution in gene expression
      studies, it is in fact based on the classic technique of Southern DNA
      hybridisation where a labelled DNA probe is hybridised to single stranded DNA
      that is bound to a solid support matrix. The truly revolutionary aspect of
      microarray analysis lies in the fact that, within a given cell population, the
      expression of tens of thousands of genes, and ultimately the entire genome, can
      be assayed simultaneously. This capability, when coupled with powerful data
      analysis software, allows researchers to rapidly compare gene expression between
      two cell populations. In the cancer field, this enables researchers to compare
      gene expression between normal and malignant cells and to identify genes that are
      differentially regulated during cancer development. Microarray data can also be
      used to categorize tumours on the basis of their molecular profile, which may
      provide important biological, diagnostic and prognostic information. As little as
      5 years ago identifying even a few differentially expressed genes may have taken
      several years and cost tens of thousands of dollars. Today microarrays can
      identify ten times the number of candidate genes in just a few months and at a
      tenth of the cost. Even so, microarray analysis is still in its infancy and the
      technology is advancing rapidly. There is little doubt that microarrays will
      revolutionize our ability to quantify the complex changes that occur in gene
      expression during cancer development. The greatest challenge that lies ahead is
      how to translate this knowledge into clinically useful diagnostic and therapeutic
      tools. In this review, we describe the technical aspects of DNA microarray
      analysis and some of the current and future applications of this technology for
      analysing gene expression in ovarian cancer.

PMID- 12044927
TI  - Proceedings of the Workshop on Regulation of Ovarian Function. Upper Hutt, New
      Zealand, August 23-24, 2001.

PMID- 12044928
TI  - Time, Cells, and Strehler. Special section in memory of Bernard L. Strehler.

PMID- 12044929
TI  - The life and contributions of Professor Bernard L. Strehler, founding editor-in
      chief of mechanisms of ageing and development, professor of biology at the
      University of Southern California (February 21, 1925-May 13, 2001).

PMID- 12044930
TI  - Bernard Strehler--inspiration for basic research into the mechanisms of aging.

PMID- 12044931
TI  - Bernard Strehler-inspiration for basic research into the mechanisms of aging.
AB  - Bernard Strehler, who passed away recently, has provided inspiration and
      intellectual guidance for a generation of scientists interested in the biology of
      aging. My own career in this field was launched in large part by the ideas and
      concepts discussed by Dr Strehler in his book, Time, Cells, and Aging. Much of my
      scientific career has been devoted to studying one aspect of the aging process
      the intracellular accumulation of autofluorescent lysosomal storage bodies
      (lipofuscin) during senescence. Work in my laboratory has contributed to the
      elucidation of the molecular mechanisms that underlie formation of lipofuscin in
      the retinal pigment epithelium of the eye. The challenge for the work on
      lipofuscin, and for much of the current research on aging, is to determine
      whether specific age-related changes such as lipofuscin accumulation, are
      involved in determining maximum life span. Bernard Strehler's eloquent statement
      of this challenge will hopefully continue to inspire new research to further our
      understanding of the aging phenomenon.

PMID- 12044932
TI  - Advice to an aging scientist.
AB  - Fifty years ago, Peter Medawar and George Williams developed two now-classic
      theories for the evolution of senescence. In the past 20 years, evolutionary
      biologists studying aging have developed explicit mathematical models of these
      theories, used these models to derive explicit predictions, and tested these
      predictions using a variety of approaches. But, we argue here, our singular focus
      on these models may have hindered progress in evolutionary studies of aging.
      Research in this area has not kept pace with dramatic advances in evolutionary
      theory and molecular genetics. Progress in evolutionary studies of aging will
      depend on a bold, integrative approach, incorporating evolutionary and molecular
      advances from other fields, along with the powerful statistical and mathematical
      tools now available. We discuss several specific examples where we may gain new
      insight into the causes of aging by looking to other evolutionary phenomena,
      including sexual conflict and the evolution of social behavior. In addition, we
      present new results which suggest that the analysis of gene networks may lend
      particular insight into the genetic underpinnings of the aging process.

PMID- 12044933
TI  - Fixation of deleterious alleles, evolution and human aging.
AB  - Human aging, like everything else in biology, only makes sense in the context of
      evolution. There is substantial agreement among evolutionary geneticists
      regarding the evolutionary underpinnings of one of the main questions of human
      aging i.e. 'Why do we age?', which involves the higher rate of fixation of
      alleles that cause deleterious post-reproductive phenotypes vs. alleles that
      cause deleterious pre-reproductive phenotypes. Even higher rates of fixation of
      deleterious mutations are predicted to occur on population genetic grounds in two
      non-recombinant genomes in humans i.e. the Y chromosome, and the mitochondrial
      genome. The added burden of deleterious mutations on the Y may explain the
      reduced average lifespan of males vs. females. A high predicted fixation rate of
      the mitochondrial genome may explain its fast rate of evolution, and the high
      frequency of mitochondrial disease in relationship to this genomes' small size,
      and may underlie the transfer of mitochondrial genes over evolutionary time to
      the nucleus. Thus a molecular evolutionary model of aging which focuses on
      increased fixation rates of (1) nuclear alleles which only have deleterious
      effects post-reproduction, (2) deleterious genes on the Y chromosome, and (3)
      deleterious genes on the mitochondrial genome, makes multiple testable
      predictions about the causes and mechanisms of aging.

PMID- 12044934
TI  - Paradigms and pitfalls of yeast longevity research.
AB  - Over the past 10 years, considerable progress has been made in the yeast aging
      field. Multiple lines of evidence indicate that a cause of yeast aging stems from
      the inherent instability of repeated ribosomal DNA (rDNA). Over 16 yeast
      longevity genes have now been identified and the majority of these have been
      found to affect rDNA silencing or stability. Environmental conditions such as
      calorie restriction have been shown to modulate this mode of aging via Sir2, an
      NAD-dependent histone deacetylase (HDAC) that binds at the rDNA locus. Although
      this mechanism of aging appears to be yeast-specific, the longevity function of
      Sir2 is conserved in at least one multicellular organism, Caenorhabditis elegans
      (C. elegans). These findings are consistent with the idea that aging is a by
      product of natural selection but longevity regulation is a highly adaptive trait.
      Characterizing this and other mechanisms of yeast aging should help identify
      additional components of longevity pathways in higher organisms.

PMID- 12044935
TI  - Long-lived mutants, the rate of aging, telomeres and the germline in
      Caenorhabditis elegans.

PMID- 12044936
TI  - Cell signaling in aging and apoptosis.
AB  - Alterations in apoptotic potential, due to perturbations in cell signaling
      cascades, could underlie age-related organ-specific cellular degeneration and
      death. While increased apoptosis could lead to cell loss, as in neuronal
      degeneration, loss of apoptosis competence might well result in the loss of
      phenotypic fidelity of somatic cells, which could explain to some extent, the age
      related increase in cancer incidence. Results from our laboratory indicate that
      after subjecting young and old rats to genotoxic stress in the form of methyl
      methanesulfonate (MMS), an apoptotic response is quickly mounted in the liver of
      the young animals but virtually absent in the same organ of old animals (Nature
      Med. 8 (2002) 3). To address the possible molecular signaling defect(s)
      responsible for the age-related dysfunction of apoptosis in response to MMS,
      mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases
      (ERKs), c-Jun NH(2)-terminal kinases (JNKs) and p38 MAPKs, were evaluated in the
      liver of young and old rats after MMS treatment. The results demonstrated
      distinct age-specific patterns of MMS-induced MAPKs activation, suggesting that
      the balance between cell survival and apoptosis after genotoxic stress may be
      impaired during aging. These results are discussed in terms of the relative
      importance in aging of biological redundancy, a concept put forward by the late
      Bernard Strehler, and cellular fidelity.

PMID- 12044937
TI  - mtLOH (mitochondrial loss of heteroplasmy), aging, and 'surrogate self'.
AB  - In tribute to Dr Strehler, an attempt is made to use a style of reasoning found
      in some of his later papers as an outline of this article. First, general
      arguments in favor of the involvement of somatic mutations in mtDNA in the aging
      process are presented. Second, evidence is provided in support of a general
      tendency of mitochondrial genomes to reach homoplasmic state at the cellular
      level, for which we propose the term mitochondrial loss of heteroplasmy (mtLOH).
      This process is likely to facilitate the involvement of mtDNA mutations in the
      aging process by streamlining the phenotypic expression of the mutant genotype.
      Third, preliminary evidence of the very high incidence of clonal deletions in
      pigmented neurons of substantia nigra is reported. This observation highlights
      the possibility that accumulation of mtDNA mutations specific in certain cell
      types of a complex tissue may account for the involvement of mtDNA mutations in
      the aging process despite the relatively low average incidence of these mutations
      in the tissue as a whole. High incidence of mtDNA deletions in pigmented neurons
      evokes Strehler's idea that efforts to delay aging may not be the most cost
      efficient way of preserving 'self awareness and a joyful sense of life', as he
      put it. A potential alternative suggested by Strehler, i.e. creation of a
      'surrogate self' by computer simulation may deserve more attention than it
      currently enjoys.

PMID- 12044938
TI  - In memoriam Bernard Strehler--genomic instability in ageing: a persistent
      challenge.
AB  - Genomic instability comprises a broad spectrum of mutational alterations in the
      genome, such as point mutations in DNA, microsatellite expansions or
      contractions, amplifications and deletions of DNA sequences, gene rearrangements
      and structural or numerical chromosomal aberrations. A substantial body of data
      demonstrates an increase of genomic instability during normal ageing. This
      includes cytogenetic changes; loss of rDNA; formation of extrachromosomal
      circular DNA species; loss of telomeric repeats; increased microsatellite
      instability; as well as point mutations and deletions in global nuclear and
      mitochondrial DNA. Evidence has accumulated supporting a causative role of
      genomic instability in ageing. Genomic instability can be counteracted by a
      number of proteins including antioxidant enzymes, the WRN protein (deficient in
      Werner syndrome), telomerase, poly(ADP-ribose) polymerase-1 and a range other
      others, as well as by multi-protein systems such as DNA mismatch repair, base
      excision repair and nucleotide-excision repair. Important research tasks for the
      future will be to elucidate how and what extent the various expressions of
      genomic instability contribute to the ageing process and to understand the
      molecular mechanisms and regulation of the above factors and pathways involved in
      limiting the induction of ageing-associated genomic instability.

PMID- 12044939
TI  - Large genome rearrangements as a primary cause of aging.
AB  - In his introductory chapter of the Mutation Research special issue on 'Genetic
      Instability and Aging', the late Bernard Strehler provided some historical
      perspectives on the long-standing hypothesis that aging is primarily caused by
      changes in the genome of somatic cells (Strehler, 1995, Mutat. Res. 338 (1995)
      3). Based on his own findings of a loss of ribosomal RNA gene copies in
      postmitotic tissues of dogs as well as humans during aging, his main conclusion
      was that deletional mutations are more likely than point mutations to be a main
      causal factor in aging. To directly assess the levels of different types of
      spontaneous mutations in organs and tissues during aging, we have used a mouse
      model harboring a chromosomally integrated cluster of lacZ-containing plasmids
      that can be recovered and analyzed in Escherichia coli. Our results indicate the
      accumulation of mutations in some but not all organs of the mouse with
      significant differences in mutational spectra. In addition to point mutations,
      genome rearrangements involving up to 66 Mb of genomic DNA appeared to be a major
      component of the mutational spectra. Physical characterization of the breakpoints
      of such rearrangements indicated their possible origin by erroneous, non
      homologous DNA double-strand break repair. Based on their increased occurrence
      during aging in some tissues and their often very large size, we have designed a
      model for an aging tissue in terms of a cellular mosaic with a gradual increase
      in genome rearrangements that leads to functional senescence, neoplastic
      transformation or death of individual cells by disrupting nuclear architecture
      and patterns of gene regulation.

PMID- 12044940
TI  - Functional recovery of senescent cells through restoration of receptor-mediated
      endocytosis.
AB  - The functional deterioration of an organism with age causes the major problem of
      maintaining the quality of life at old age. Degenerative changes in the organism
      may to some extent reflect alterations that can be observed in cells during in
      vitro replicative senescence. At the cellular level, the receptor-mediated
      endocytosis in the membrane might be emphasized as a responsible mechanism for
      functional decay, since the endocytosis is in charge of many important biological
      phenomena: nutrient uptake, growth factor sensitivity, immune response,
      protection from environment and pathogen uptake, etc. We found that two major
      endocytotic pathways, i.e. clathrin-mediated and caveolae-dependent endocytosis,
      are down regulated in senescent cells. For the down regulation of the clathrin
      dependent receptor-mediated endocytosis, the reduction of amphiphysin-1 was found
      responsible, which was confirmed by Western blot analysis, dominant negative
      mutant transfection and restoration of gene activity by microinjection. With
      respect to the hypo-responsiveness of senescent cells to growth factors, the
      upregulation of caveolins has been suggested to be a causal factor. The
      overexpression of caveolins caused senescent-like changes in epidermal growth
      factor (EGF) response of the young cells, while down regulation of caveolins by
      use of antisense-oligonucleotides restored the EGF response in old cells,
      suggesting that caveolin system would be one of the major mechanisms responsible
      for decreased responses to growth factors in the senescent cells. Based on these
      results, it can be suggested that the functional deterioration of the senescent
      cells may be explained in terms of the down regulation of receptor mediated
      endocytosis, at least in part, and that the restoration of endocytosis apparatus
      either with amphiphysin supplementation or with reduction of caveolins might lead
      to functional recovery of the senescent cells.

PMID- 12044941
TI  - Genetics of cellular senescence.
AB  - Cellular senescence or replicative senescence is a state of irreversible growth
      arrest that somatic cells enter as a result of replicative exhaustion. This can
      be mimicked by culture manipulations such as Ras oncogene overexpression or
      treatment with various agents such as sodium butyrate and 5-azacytidine. It is
      believed that cellular senescence is one of the protective mechanisms against
      tumor formation. Genetic analyses of cellular senescence have revealed that it is
      dominant over immortality because whole cell fusion of normal with immortal cells
      yields hybrids with limited division potential. Only four complementation groups
      for indefinite division have been identified from extensive studies fusing
      different immortal human cell lines with each other. The senescence-related genes
      for three of the complementation groups B-D have been identified on human
      chromosomes 4, 1, and 7, respectively, by microcell-mediated chromosome transfer,
      though the existence of senescence-related genes on other chromosomes has been
      suggested. MORF4 was cloned as the senescence-related gene on human chromosome 4
      and is a member of a new gene family, which has multiple transcription factor
      like motifs. This gene family may affect cell division by modulating gene
      expression. Study of this novel gene family should lead to new insights regarding
      the mechanisms and function of cellular senescence in aging and immortalization.

PMID- 12044942
TI  - Approach of evolutionary theories of ageing, stress, senescence-like phenotypes,
      calorie restriction and hormesis from the view point of far-from-equilibrium
      thermodynamics.
AB  - B. L. Strehler wrote that "Any system that is not in thermodynamic equilibrium
      will approach that state at a rate that is a function of absolute temperature and
      the energy barriers to the rearrangements of components". Far-from-equilibrium
      thermodynamics allows a global systemic description of the cellular behaviour.
      This approach transcends the genetic and stochastic considerations on ageing as
      well as some evolutionary questions about ageing. The fundamental difference
      between the processes of development and ageing could reflect the intrinsic
      differences existing between biological systems where an increase in specific
      entropy production (SEP) is, respectively, still possible or not. The increase of
      the potential of SEP which probably occurred with evolution might explain in part
      why life span could increase. However, this SEP-driven increase in life span was
      possible only in those species which did not take advantage of their increased
      potential of SEP to ameliorate their reproductive capacity at the expense of
      possible increases in repair capacity. The criteria of stability of far-from
      equilibrium open systems and the theory of attractors also help to sort the
      possible types of cellular stress responses: normal ageing, hormesis, stress
      induced premature senescence, apoptosis or necrosis.

PMID- 12044943
TI  - Brain evolution and lifespan regulation: conservation of signal transduction
      pathways that regulate energy metabolism.
AB  - Mechanisms for sensing, acquiring, storing and using energy are fundamental to
      the survival of organisms at all levels of the phylogenetic scale. Single-cell
      organisms evolved surface receptors that sense an energy source and, via signal
      transduction pathways that couple the receptors to the cell cytoskeleton move
      towards the energy source. Mutlicellular organisms evolved under conditions that
      favored species that developed complex mechanisms for obtaining food, with
      nervous systems being critical mediators of energy acquisition and regulators of
      energy metabolism. A conserved signaling system involved in regulating cellular
      and organismal energy metabolism, and in sensing and responding to energy/food
      related environmental signals, involves receptors coupled to the
      phosphatidylinositol-3-kinase-Akt signaling pathway. Prominent activators of this
      pathway are insulin, insulin-like growth factors and brain-derived neurotrophic
      factor (BDNF). Recent studies in diverse organisms including nematodes, flies and
      rodents have provided evidence that insulin-like signaling in the nervous system
      can control lifespan, perhaps by modulating stress responses and energy
      metabolism. Interestingly, the lifespan-extending effect of dietary restriction
      in rodents is associated with increased BDNF signaling in the brain, and a
      related increase of peripheral insulin sensitivity, suggesting a mechanism
      whereby the brain can control lifespan. Thus a prominent evolutionarily conserved
      function of the nervous system is to regulate food acquisition and energy
      metabolism, thereby controlling lifespan.

PMID- 12044944
TI  - The frail elderly: role of dendritic cells in the susceptibility of infection.
AB  - The decline in immunity in the elderly has largely been attributed to impairment
      of T cell mechanisms. This seems reasonable since the thymus involutes with age,
      so that the number of naive cells to respond to new foreign antigens also
      declines. However, little is known about how aging affects antigen-presenting
      cells (APC) that are responsible for the initiation and outcome of effector T
      cell immune responses. This review focuses on the age-related alterations of a
      key APC, the dendritic cell (DC). Recent findings suggest that interleukin-10, a
      key cytokine that can suppress cell mediated immunity and maturation of DC
      subsets, is elevated in the very healthy elderly. However, production of IL-12,
      required for the initiation of T cell immune responses, declines in frail elderly
      along with DC antigen presenting function. These findings suggest that shifts in
      IL-10 and IL-12 may not only directly influence immune response but may also
      alter the balance and maturation of DC subsets. Finally, study of immunologic
      differences between the very healthy and frail elderly may reveal important
      changes in DC function and regulation influenced by age and/or environment
      (disease, nutrition, medications, etc.).

PMID- 12044945
TI  - Beneficial influences of systemic cooperation and sociological behavior on
      longevity.
AB  - During his long research career in the field of aging, Dr Bernard Strehler
      developed a series of theories concerning the identity of genes that can promote
      longevity and their role in natural selection. As a tribute to Dr Strehler, we
      have taken this opportunity to summarize a selection of these theories and to
      illustrate how these insights have influenced our search for longevity genes
      within the immune system. The identification of longevity genes has proven
      difficult. We believe that, at least in part, this reflects the emphasis on the
      concept of survival of the 'physically' fittest. We have used the immune system
      as a model to demonstrate that, over and above the self-evident advantage of
      those genes that contribute the attributes commonly associated with survival of
      the 'physically' fittest, those genes that lead to a predisposition to cooperate
      also confer a competitive survival advantage. As the acquisition of cooperativity
      in a society is linked to support mechanisms provided by older individuals, the
      search for longevity genes should not be limited to those genes that are
      associated with extended expression of a youthful phenotype. Rather these studies
      should be expanded to include identification of those genes that regulate
      physiologic parameters that affect individual longevity, even if they do not
      correspond with the traditional view of reproductive competitiveness. At the
      societal level, longevity genes may encode attributes that regulate sociologic or
      psychological parameters that may contribute to a tendency to non-aggressive or
      cooperative behavior that leads to achievement of common goals necessary for the
      survival of the species. This view of the selection for longevity impacts the
      analysis of longevity genes and aging at the organismal level. Dr Strehler viewed
      organismal aging as an integrated functional state, in which he conceived the
      outcome as reflecting the net balance of functional decrementers and evolved
      compensatory features. We propose that, in more evolved species, the longevity
      genes will be those genes, or sets of genes, that counterbalance of age-related
      functional decrementers with the age-related manifestation of evolved
      compensatory features. Thus, as illustrated here through analysis of the immune
      system, the longevity genes may well be those genes that promote overall systemic
      cooperation and compensation within the immune system and associated systems,
      rather than the genes that prevent age-related alterations in only one or a
      limited number of pathways.

PMID- 12044947
TI  - Human premature aging syndromes and genomic instability.

PMID- 12044948
TI  - Proceedings of the 5th International NILS (National Institute for Longevity
      Sciences) Workshop on Longevity Sciences. Aichi, Japan, 30 November-1 December
      2000.

PMID- 12044946
TI  - Immunological memory and late onset autoimmunity.
AB  - This review will address a paradox that has long fascinated scientists studying
      the effects of aging on the immune system. Although it has been clearly
      documented that B and T lymphocytes lose the ability to respond to antigenic or
      mitogenic stimulation with age, it has nonetheless been noted that the frequency
      of autoreactive antibodies is higher in older individuals. Given that the
      majority of the age-associated defects in immune regulation target the naive T
      and B lymphocyte subsets, it has been presumed that this increase in antibodies
      specific for self antigens was due to changes in the B cell repertoire and/or to
      differences in the mechanisms responsible for generating immune tolerance in
      primary responses. However, in this review, we will address an alternative
      possibility that memory immune responses, first generated when the individual was
      young, may play a critical role in the appearance of serum autoantibodies by
      reactivation later in life (recall memory). It has recently been shown, in
      several different systems, that memory immunity can be maintained over the
      lifetime of the animal. Thus, memory B cells which are self-reactive may be
      harbored within an organism as it ages and the potential exists that they become
      re-activated at a later time, resulting in a vigorous autoreactive recall
      response. This may occur preferentially in older individuals due to several
      factors, including deficiencies in immune tolerance with age, progressive age
      associated loss of tissue integrity yielding neo-self antigens, and possible re
      exposure to an infectious agent which induces an autoimmune memory response
      through molecular mimicry. Thus, we propose that some of the autoantibodies seen
      in elderly patients and in older animals may have been produced by memory
      lymphocytes originally generated against antigens encountered during one's youth,
      but maintained in a tolerant (non reactive) state until a subsequent triggering
      event occurs. Possible implications of this model will be discussed.

PMID- 12044949
TI  - Bioavailablility of elderberry anthocyanins.
AB  - Considerable epidemiological evidence suggests a link between the consumption of
      diets rich in fruits and vegetables and a decreased risk of cardiovascular
      disease and cancers. Anthocyanins have received attention as important dietary
      constituents that may provide health benefits and contribute antioxidant capacity
      beyond that provided by essential micronutrients such as ascorbate, tocopherols,
      and selenium. The emergence of renewed interest by industrial countries in
      traditional herbal medicines and the development of 'functional foods' are
      stimulating the need for more information regarding the bioavailability and
      efficacy of plant polyphenols. Flavonoids represent a numerous group of secondary
      plant metabolites based on the structure of a pyran ring flanked by two or more
      phenyl rings and varying subtly in the degree of unsaturation and the pattern of
      hydroxylation or methylation. Flavonoids also vary in the type of sugar attached
      or the degree of polymerization. Anthocyanins, potent flavonoid antioxidants
      widely distributed in fruits, vegetables and red wines, normally occur in nature
      as glycosides, a form not usually considered as bioavailable. We have examined
      the bioavailability and pharmacokinetics of anthocyanins in humans. Anthocyanins
      were detected as glycosides in both plasma and urine samples. The elimination of
      plasma anthocyanins appeared to follow first-order kinetics and most anthocyanin
      compounds were excreted in urine within 4 h after feeding. The current findings
      appear to refute assumptions that anthocyanins are not absorbed in their
      unchanged glycosylated forms in humans.

PMID- 12044950
TI  - Reactive oxygen and nitrogen species and cellular and organismal decline:
      amelioration with melatonin.
AB  - Cellular and organismal decline is, in part, believed to be a consequence of
      oxygen and nitrogen-based reactants which persistently damage macromolecules
      throughout a lifetime. The resulting accumulation of damaged molecules eventually
      seriously compromises essential functions of cells leading to their death.
      Excessive cellular loss causes deterioration of organ function and inevitably to
      the demise of the organism. The sequence of events, known as the free radical
      theory of aging, is widely espoused by biological gerontologists. Antioxidants
      are commonly employed to combat molecular damage mediated by oxygen and nitrogen
      based reactants. One of these protective agents is melatonin. Melatonin has
      several distinct advantages as a preserver of organelle structure and function.
      It is widely distributed in organisms and within cells. It works via a number of
      mechanisms to reduce oxidative damage. Thus, melatonin scavenges a number of
      reactants including the hydroxyl radical (*OH), hydrogen peroxide (H(2)O(2)),
      nitric acid (NO*), peroxynitrite (ONOO(-)) and peroxynitrous acid (ONOOH). One of
      the products of melatonin's interaction with H(2)O(2), i.e., N(1)-acetyl-N(2)
      formyl-5-methoxykynuramine (AFMK), is also a highly efficient radical scavenger.
      The cascade of reactions where the secondary metabolites are also effective
      scavenges is believed to contribute to melatonin's high efficacy in reducing
      oxidative damage. Besides its direct scavenging actions, melatonin stimulates
      several antioxidative enzymes including superoxide dismutase, glutathione
      peroxidase and glutathione reductase in addition to inhibiting a proxidative
      enzyme, nitric oxide synthase. This combination of actions assists melatonin in
      protecting cells from the degenerative changes normally associated with aging and
      age-related diseases.

PMID- 12044951
TI  - Nitrones, their value as therapeutics and probes to understand aging.
AB  - The nitrone-based free radical traps have significant potential in the treatment
      of neurodegenerative diseases as well as in the prolongation of life span. The
      mass action free radical trapping activity of these compounds is the property,
      which first brought them to the attention of the scientific community.
      Nevertheless extensive research has demonstrated that these reactions are not
      responsible for their therapeutic mechanistic basis of activity. Rather the
      mechanism of action in the case of their neuroprotective activity appears to
      involve the inhibition of enhanced signal transduction processes that mediate the
      upregulation of genes, which produce neurotoxic products. The most widely used
      compound in this series, alpha-phenyl-tert-butyl-nitrone (PBN), has been shown to
      extend life span in three published studies, i.e. two mouse models and one rat
      model. Significant prolongation of life span was noted in all three studies. We
      report the summary of a recent study with a novel nitrone, CPI-1429, which
      demonstrated the ability to extend life span even though administration of the
      compound was begun in older animals. Despite these promising studies, much more
      rigorous research examining the anti-aging activity of the nitrones needs to be
      conducted. It is not known exactly why the nitrones possess anti-aging activity.
      They have been shown to quell enhanced signal transduction processes associated
      with enhanced pro-inflammatory cytokine mediated events. The nitrones interfere
      in some unknown steps preventing receptor triggered MAP kinase phosphorylation
      cascades. Stabilization of phosphorylation networks associated with checkpoint
      proteins could slow cell cycle processes and this could be the basis of the
      nitrones anti-senescent activity.

PMID- 12044952
TI  - Effect of red wine polyphenols on vascular smooth muscle cell function--molecular
      mechanism of the 'French paradox'.
AB  - Red wine polyphenols (RWP) have been shown to have an anti-atherogenic activity
      mainly through anti-oxidative effects on low-density lipoprotein (LDL) oxidation.
      Though proliferation of vascular smooth muscle cells (VSMC) is critical to
      atherosclerosis formation, the effect of RWP on VSMC proliferation has not been
      elucidated. In this study, we investigated whether RWP, which extracted from red
      wine using column chromatography, could affect the 10% serum-stimulated VSMC
      proliferation. Treatment with RWP showed a potent inhibitory effect on the
      proliferation and DNA syntheses is in cultured rat VSMC. In contrast, the
      inhibitory effect of RWP on the proliferation of bovine vascular endothelial
      cells (EC) was only observed at much higher doses. Moreover, RWP significantly
      inhibited the proliferation and DNA synthesis of human VSMC but no human vascular
      EC in a dose-dependent manner. To elucidate the molecular mechanisms of these
      anti-proliferative effects of RWP on VSMC, but not on vascular EC, we
      investigated the effects of RWP on the cell cycle regulation. RWP downregulated
      the expression and promoter activity of cyclin A gene, one of cell cycle
      regulators. In addition, RWP inhibited the binding of nuclear proteins to the
      activating transcription factor (ATF) site in the cyclin A promoter, and
      downregulated the expression of transcription factors, cyclic AMP-responsive
      element binding protein (CREB) and ATF-1. In conclusion, these results
      demonstrate one possible finding that the anti-proliferative effect of RWP on
      VSMC may be associated with the downregulation of cyclin A gene expression
      through the inhibition of transcription factor expression.

PMID- 12044953
TI  - Effects of antioxidants on kidney disease.
AB  - Kidney mesangial cells (MCs) and vascular smooth muscle cells (VSMCs) are closely
      related in terms of origin, microscopic anatomy, histochemistry, and
      contractility. This relationship suggests a similarity between kidney glomerular
      sclerosis and atherosclerosis. Vitamin E appears beneficial in the prevention and
      treatment of coronary disease and also inhibits the proliferation of VSMCs in
      vitro. We used vitamin E and probucol to treat glomerular sclerosis and MC
      proliferative glomerulonephritis (GN) in two animal models of glomerular disease.
      Using rats, a remnant kidney model accelerated with hyperlipidemia was employed
      to reflect progressive glomerular sclerosis leading to chronic renal failure, and
      an anti-thymocyte serum treatment was used to model acute MC-proliferative GN.
      Supplemental dietary antioxidants suppress MC proliferation and glomerular
      sclerosis in models of glomerular disease in rats. These results suggest that
      treatment with antioxidants may be a promising intervention to prevent
      progression of kidney disease.

PMID- 12044954
TI  - The pathogenesis of HIV-induced dementia.

PMID- 12044955
TI  - Animal models and possible human application of immunological restoration in the
      elderly.
AB  - Autopsy reports by pathologists in geriatric hospitals reveal that the leading
      direct cause of death in the elderly over 65 years of age are infectious diseases
      such as pneumonia and urinary tract infection, neither cancer nor vascular
      diseases in the brain and heart. This indicates that severe impairment of immune
      functions is developing in the elderly people. The impairment of immune functions
      does not occur abruptly in the elderly people. The immune function starts to
      decline as early as at the 2nd decades, showing approximately 50 and 90% decline
      at the 5th and 8th decades, respectively. Thus, immunological restoration is
      acutely needed for the improvement of their general health condition of the
      elderly. This report communicates several methods of immunological restoration
      using animal models and suggests possibilities of human application. Methods
      presented are: (1) a low dose of cyclophosphamide; (2) vitamin E; (3) Japanese
      herbal medicines; (4) caloric restriction and exercise; (5) vaccine; (6) oral
      administration of antigens; (7) grafting of cells and tissues, including a future
      program. Discussion will be made on the possibilities of these methods for human
      application.

PMID- 12044957
TI  - Novel neuroprotective anti-Alzheimer drugs with anti-depressant activity derived
      from the anti-Parkinson drug, rasagiline.
AB  - A number of studies have shown that the selective monoamine oxidase (MAO)-B
      inhibitor l-selegiline has neuroprotective activities in several cell culture
      systems and in vivo. The suggestion has been made that the propargyl moiety in
      this molecule may have some intrinsic neuroprotective activity not related to its
      ability to bind covalently to MAO B and inhibit it. We have therefore developed a
      number of novel drugs based on rasagiline (N-propargyl-1R-(+)-aminoindan), a
      potent anti-Parkinson-propargyl-containing MAO-B inhibitor drug with structural
      resemblance to selegiline, for the treatment of Alzheimer's disease. These drugs
      possess a carbamate moiety for cholinesterase (ChE), and a propargyl group for
      MAO inhibition. The R-enantiomer of these compounds (TV3326) has ChE and MAO
      inhibitory activities in vivo and retains the neuroprotective properties of
      rasagiline. It also exhibits anti-depressant activity in animal models. The S
      enantiomer does not inhibit MAO and has no anti-depressant activity, but it has
      similar ChE inhibitory and neuroprotective activities. Thus MAO inhibition by
      propargylamines is not a pre-requisite for neuroprotection. Rather,
      propargylamines have some intrinsic neuroprotective property whose mechanism of
      action requires further elucidation.

PMID- 12044956
TI  - Modulation of neuroendocrine--immune signaling by L-deprenyl and L
      desmethyldeprenyl in aging and mammary cancer.
AB  - The aging process is characterized by a decline in cellular functions of diverse
      systems of the body, including the neuroendocrine-immune network. One
      neuroendocrinological theory of aging is based on findings that the loss of
      hypothalamic neurotransmitter functions and an imbalance in hormonal secretion
      contribute to the cessation of reproductive cycles and the development of mammary
      and pituitary tumors. One potential cause of immunosenescence is an age-related
      decline in the regulatory functions of sympathetic noradrenergic nerve fibers
      whose neurotransmitters signal lymphoid cells in the bone marrow, thymus, spleen,
      and lymph nodes. In addition to impairment caused by the generation of free
      radicals during numerous biochemical processes, there is a shift in the pro
      oxidant/anti-oxidant balance resulting in cellular oxidative stress and hastening
      the aging process. Altered interactions between the neuroendocrine system and the
      immune system are associated with increased incidence, development, and growth of
      breast cancer and other neoplastic diseases. We have demonstrated that the
      disruption in the neuroendocrine-immune interactions in old rats, and in female
      rats with mammary tumors, can be reversed by deprenyl, a monoamine oxidase
      inhibitor. Deprenyl treatment leads to enhanced central and peripheral
      catecholaminergic activity and a readjustment of immunological responses. In this
      brief review, the nature and changes in the bi-directional communication between
      the neuroendocrine system and immune system and the possible mechanism(s) of
      actions of deprenyl in restoring these interactions during aging and mammary
      cancer are discussed.

PMID- 12044958
TI  - Why (--)deprenyl prolongs survivals of experimental animals: increase of anti
      oxidant enzymes in brain and other body tissues as well as mobilization of
      various humoral factors may lead to systemic anti-aging effects.
AB  - (--)Deprenyl, a monoamine oxidase B (MAO B) inhibitor is known to upregulate
      activities of anti-oxidant enzymes such as superoxide dismutase (SOD) and
      catalase (CAT) in brain dopaminergic regions. The drug is also the sole chemical
      which has been repeatedly shown to increase life spans of several animal species
      including rats, mice, hamsters and dogs. Further, the drug was recently found to
      enhance anti-oxidant enzyme activities not only in brain dopaminergic regions but
      also in extra-brain tissues such as the heart, kidneys, adrenal glands and the
      spleen. We and others have also observed mobilization of many humoral factors
      (interferone (INF)-gamma, tumor necrosis factor (TNF)-alpha, interleukine (IL)
      1beta,2,6, trophic factors, etc.) and enhancement of natural killer (NK) cell
      functions by (-)deprenyl administration. An apparent extension of life spans of
      experimental animals reported in the past may be better explained by these new
      observations that (-)deprenyl upregulate SOD and CAT activities not only in the
      brain but also in extra-brain vital organs and involve anti-tumorigenic as well
      as immunomodulatory effect as well. These combined drug effects may lead to the
      protection of the homeostatic regulations of the neuro-immuno-endocrine axis of
      an organism against aging.

PMID- 12044959
TI  - Mechanism of action of anti-aging DHEA-S and the replacement of DHEA-S.
AB  - The plasma ACTH and cortisol levels do not change during aging. On the other
      hand, the plasma dehydroepiandrosterone sulfate (DHEA-S) changes remarkably
      during aging. Before puberty, the plasma DHEA-S level both in males and females
      is very low, however, it rapidly increases at puberty, and thereafter
      significantly decreases both linearly and age-dependently. Cytochrome P450c17 has
      two enzyme activities, 17-alpha-hydroxylase and 17,20-lyase. Cortisol is
      synthesized by 17-alpha-hydroxylase, and DHEA is synthesized by 17,20-lyase. The
      mechanism of dissociation of cortisol and DHEA synthesis in aging depends on
      another regulator of 17,20-lyase of cytochrome P450c17 such as cytochrome P450
      reductase. We demonstrated significant decrease in cytochrome P450 reductase
      activity in bovine aged adrenal glands. We clarified the beneficial effects of
      DHEA as an anti-aging steroid based on both in vitro and in vivo experiments,
      such as the stimulatory effect of immune system, anti-diabetes mellitus, anti
      atherosclerosis, anti-dementia (neurosteroid), anti-obesity and anti
      osteoporosis. It is very important to identify the mechanism of action of DHEA.
      We clarified the conversion of DHEA to estrone by cytochrome P450 aromatase in
      primary cultured human osteoblasts. We indentified high affinity of DHEA binding
      with K(d)=6.6 nM in antigen and DHEA stimulated human T lymphocytes. We searched
      for the target genes that are specifically induced in activated T lymphocytes in
      the presence of DHEA by subtractive hybridization screening for differentially
      expressed transcripts. The double blind, randomized human replacement therapies
      utilizing DHEA are also reviewed.

PMID- 12044960
TI  - Dehydroepiandrosterone (DHEA) as a possible source for estrogen formation in bone
      cells: correlation between bone mineral density and serum DHEA-sulfate
      concentration in postmenopausal women, and the presence of aromatase to be
      enhanced by 1,25-dihydroxyvitamin D3 in human osteoblasts.
AB  - A significant positive correlation between bone mineral density (BMD) and serum
      dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51
      99 years old) but no correlation was seen between BMD and serum estradiol. In
      subset analysis, strong positive correlation of serum DHEA-S and estrone with BMD
      was observed in postmenopausal women aged less than 69 years old. To study a
      possible role of DHEA-S in preventing osteoporosis, we characterized aromatase
      activity converting androgens to estrogens in human osteoblasts, because
      postmenopausal women maintain considerable levels of adrenal androgens.
      Glucocorticoids at 10(-9) to 10(-7) M induced transiently the expression of and
      the enzymatic activity of aromatase cytochrome P450 (P450AROM) in primary
      cultured osteoblasts. 1,25-Dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) alone did not
      induce the aromatase activity, but enhanced and maintained the glucocorticoid
      induced P450AROM gene expression. Analysis of the activity of P450AROM gene 1b
      (I.4) promoter, which is used dominantly in human osteoblasts, indicated that the
      region from -888 bp to -500 bp, which does not contain a typical vitamin D
      responsive element, is responsible for the enhancing effect of 1,25-(OH)(2)D(3).
      These results may suggest that adrenal androgen, DHEA, is converted to estrone in
      osteoblast by P450AROM, which is positively regulated by glucocorticoid and 1,25
      (OH)(2)D(3), and is important in maintaining BMD in the sixth to the seventh
      decade, after menopause.

PMID- 12044961
TI  - AGEID: a database of aging genes and interventions.
AB  - The aging genes/interventions database (AGEID) is a database of experimental
      results related to aging. AGEID is available as part of the science of aging
      knowledge environment on the World Wide Web at
      http://sageke.sciencemag.org/cgi/genesdb. The goal of AGEID is to catalog, in one
      location, every published experiment where life span has been measured in any
      organism. AGEID also includes information on genes that influence the incidence
      of age-associated disorders such as Alzheimer's disease and Parkinson's disease.
      AGEID gene/intervention reports are formatted pages containing the organism and
      strain background in which the particular experiment was performed, the type of
      genetic or environmental perturbation, the effect on life span, a description of
      the gene function and its role in longevity, protein homologs, and references.
      The use of this database by researchers who study aging should facilitate easy
      comparison of the genes and interventions that affect life span in different
      organisms.

PMID- 12044962
TI  - Dietary restriction reduces atherosclerosis and oxidative stress in the aorta of
      apolipoprotein E-deficient mice.
AB  - Dietary restriction (DR) has been shown to inhibit almost all the age-related
      diseases, e.g. cardiomyopathy and cancers, in rodents. However, there is little
      information for the effect of DR on atherosclerosis. In the present study, we
      examined the effect of DR on the development of atherosclerosis in mice
      homozygous knockout for apolipoprotein E gene (ApoE(-/-)). The ApoE(-/-) mice
      were fed either ad libitum (AL) or 60% of the diet consumed by the mice fed AL.
      Atherosclerotic lesions in the proximal aorta of these mice were measured. Our
      results showed that ApoE(-/-) mice fed the calorie-restricted diet had smaller
      and relatively early stages of atherosclerotic lesions (e.g. foam cells and free
      lipids) when compared to ApoE(-/-) mice fed AL, who developed more advanced
      lesions (e.g. fibrous caps and acellular areas). In addition, ApoE(-/-) mice fed
      the calorie-restricted diet showed a significant decrease in the level of lipid
      hydroperoxides and the production of superoxide and hydrogen peroxide in the
      aorta as compared to ApoE(-/-) mice fed AL. These observations suggest that
      reduction of oxidative stress in the arterial wall may contribute to the anti
      atherogenic effect of DR in ApoE(-/-) mice.

PMID- 12044963
TI  - Identification of high caspase-3 mRNA expression as a unique signature profile
      for extremely old individuals.
AB  - Apoptosis, or programmed cell death, is important for maintaining tissue
      homeostasis, as it permits the elimination of damaged, functionless or unwanted
      cells. As we age, our immune system undergoes constant remodeling, during which
      age-associated changes in immune parameters, including decreased naive and
      increased memory T cells, have been reported. However, excessive immune cell
      loss, rendering the elderly more vulnerable to infections, and inappropriate
      deletion of damaged or functionless lymphocytes, can contribute to the
      development of age-associated diseases. As such, we studied the mRNA expression
      of cell death (specifically caspase) genes in nonagenarians and centenarians,
      successful models of ageing who have survived or avoided age-associated diseases,
      as well as in their younger counterparts and found that population composed of
      extremely old individuals shows a unique pattern of caspase mRNA expression,
      characterized by high levels of caspase-1 and -3, and low levels of caspase-8,
      mRNA while those composed of old individuals are characterize by high level of
      caspase-8 mRNA expression. Furthermore, we show that the described changes in
      caspases mRNA do not appear to results from age-related changes in PBMC
      composition, such as decreases in CD24. Therefore, we suggest that unique
      patterns of caspase mRNA results from the regulation of message abundance on a
      per cell basis, via a putative regulation of caspase genes at the transcription
      or RNA processing level, rather than changes in immune profiles.

PMID- 12044965
TI  - The 'intestinal-renal' arginine biosynthetic axis in the aging rat.
AB  - It has been suggested that L-arginine availability declines with advanced age,
      which could contribute to the endothelial dysfunction and decreased nitric oxide
      (NO) production that are features of aging. L-Arginine is made in the kidney and
      since the aging kidney develops progressive injury there may be decreased
      synthesis limiting availability. In this study we investigated the impact of
      aging on the regulation, at the gene level, of the various enzymes that
      synthesize L-arginine in the kidney (argininosuccinate synthetase and
      argininosuccinate lyase) and citrulline, the precursor of L-arginine made in the
      small intestine (phosphate-dependent glutaminase, carbamyl phosphate synthetase-1
      and ornithine transcarbamylase). Studies were in young (3-5 months), middle-aged
      (11-13 months) and old (18-22 months) male and female Sprague-Dawley rats aged
      under barrier conditions. The plasma, renal cortical and brain cerebellar levels
      of L-arginine are unchanged in the old male rat, and expression of the genes
      involved in renal arginine synthesis and small intestinal citrulline synthesis is
      unchanged or upregulated with age in both males and females. This study shows
      that the synthesis of L-arginine is maintained with aging despite developing
      kidney damage. Therefore, the reduced NO generating capacity that occurs in aging
      must be due to downstream changes in the NO biosynthesis pathway, such as reduced
      abundance of NO biosynthetic enzymes.

PMID- 12044966
TI  - Age-associated decrease in virus-specific CD8+ T lymphocytes during primary
      influenza infection.
AB  - The mechanism of the age-associated decrease in CD8+ T cell response of mice to
      virus infection was examined in young adult (6 months) and aged (22 months)
      C57BL/6 mice during primary pulmonary influenza A virus infection. A significant
      age-associated decrease in both the percentage (P<0.0001) and number (P<0.05) of
      CD8+ T cells binding MHC Class I tetramers containing influenza A nucleoprotein
      (NP) epitope and in virus-specific CTL activity (P<0.05) was observed with
      pulmonary lymphocytes. The percentage of NP+CD8+ cells of individual mice
      strongly correlated with NP-specific cytotoxic activity (r(2)=0.77, P<0.02) and
      with the percentage of CD8+ cells that produced interferon-gamma (r(2)=0.86,
      P<0.002) in both young and aged mice. Comparable expression of the CD28, CD25,
      and the memory CD44(hi)/CD62L(lo) phenotype was detected on NP+CD8+ lymphocytes
      from mice of both age groups. There was a delay in the maximal expansion of
      NP+CD8+ cells in aged compared to young mice that paralleled a delay in maximal
      cytotoxic activity and in virus clearance. These data suggest that the age
      related impairment of CD8+ lymphocyte activity during a primary influenza A
      infection is due to a defect in the expansion, rather than in effector activity,
      of influenza-specific CD8+ T cells.

PMID- 12044964
TI  - Age-related change in thymic T-cell development is associated with genetic loci
      on mouse chromosomes 1, 3, and 11.
AB  - Age-related decline in thymic T-cell development in 22-month-old C57BL/6J X
      DBA/2J (BXD) recombinant inbred strains of mice was functionally and
      phenotypically analyzed and genetically mapped. There was a positive correlation
      of the concanavalin A (Con A)-induced thymocyte proliferative response with the
      capability of thymocytes to mature to the CD4(+)CD8(+) stage. The accumulation of
      CD4(-)CD8(-) stage of thymocytes in 22-month-old BXD mice was further identified
      to be associated with a developmental block between the CD25(-)CD44(+) and the
      CD25(+)CD44(+) stages. The quantitative trait loci regulating the Con A-induced
      thymocyte proliferative response were mapped to mouse chromosome 1, 3, and 11,
      nearest to 32.1 centimorgan (cM), 5.6 cM, and 18.0 cM, respectively. Our results
      suggest that several genetic loci regulate the intra-thymic T-cell maturation
      process and play an important role in determining age-related decline in thymic T
      cell development.

PMID- 12044968
TI  - Effects of aging on hypothalamic-pituitary-adrenal system function in non-human
      primates.
AB  - The study was aimed at characterizing the changes in hypothalamic-pituitary
      adrenal (HPA) axis function during aging in monkey models (Papio hamadryas and
      Macaca mulatta). It has been established by specific radioimmunoassay and enzyme
      immunoassay that basal plasma levels of adrenal androgenes
      (dehydroepiandrosterone-DHEA, dehydroepiandrosterone sulfate-DHEAS) and the early
      precursors of steroid hormones (pregnenolone and 17-hydroxypregnenolone)
      progressively decrease with age in baboons and macaques, while cortisol and 11
      desoxycortisol concentrations do not change. The old female rhesus monkeys
      exhibited a higher cortisol and corticosterone response, but a lower DHEAS
      response to corticotropin-releasing hormone (CRH) administration then the young
      monkeys. The aged rhesus monkeys also exhibited a decrease of the adrenal cortex
      resiliency, that was manifested in the deceleration of the decrease of cortisol
      concentrations after the peak values had been reached in response to ACTH 1-39
      administration. At the same time the ACTH 1-24 depot test revealed no age-related
      changes in the maximum capacity of monkey adrenals to synthesize and secrete
      cortisol. The aged monkeys also developed less sensitivity of the HPA axis to
      dexametasone suppression test. The age-related hormonal changes may play an
      important role in the age-related involutive processes and in the disorders of
      the adaptive ability of old organisms.

PMID- 12044967
TI  - Age-related changes of cholesterol and dolichol biosynthesis in rat liver.
AB  - Ageing has been defined as a gradually decreased ability to maintain homeostatic
      potential and increased risk to die, associated with a tissue accumulation of
      altered proteins and lipids. Among other, increased concentration of an
      isoprenoid compound, dolichol (Dol), in mammalian tissues during ageing has been
      reported and it has been considered as a new biomarker of ageing. However, the
      mechanism and the role of this accumulation is still unknown. Aim of this work
      was to study the mechanism of age-dependent Dol accumulation in the liver
      analysing the activity of the hepatic rate-limiting enzyme of isoprenoid
      biosynthesis, the 3-hydroxy 3-methylglutaryl CoA reductase (HMGCoA reductase),
      the Dol synthesis by mevalonate (MVA), the Dol level in the plasma, and the
      cholesterol (Chol) synthesis and content of ageing rat fed ad libitum (AL) or
      subjected to the effect of food restriction. Since the caloric restrictions are
      the most reproducible way to slow ageing and to extend life span, animals on
      these nutritional regimens were used to study ageing related mechanisms. The data
      show that during ageing the hepatic Dol accumulation is associated with an
      increase of HMGCoA reductase activity, which is affected by diet restriction, and
      with an increase of MVA incorporation in Dol and Chol, which is not. In addition,
      the liver of aged rats maintains the capability to regulate its Chol content and
      to modify Chol delivery into the blood.

PMID- 12044969
TI  - Expression of Golli proteins in adult human brain and multiple sclerosis lesions.
AB  - It has been suggested that Golli proteins, structurally related to myelin basic
      proteins (MBPs), have a role in autoimmune processes. We studied the expression
      of these proteins in multiple sclerosis (MS) and determined that the number of
      Golli-immunoreactive (ir) cells was significantly higher around lesions of
      chronic MS than in control white matter. Golli proteins were expressed in the
      adult oligodendrocyte precursor cells (OPCs), activated microglia/macrophages,
      and some demyelinated axons around MS lesions. Their expression in adult OPCs
      indicates remyelination attempts, whereas the expression in the subpopulation of
      microglia/macrophages suggests roles in the immune processes of MS. In addition,
      Golli proteins may be markers of axonal transection, which is characteristic for
      MS.

PMID- 12044970
TI  - Targeting peptides for microglia identified via phage display.
AB  - Screening with a 7-mer phage display peptide library, a panel of cell-targeting
      peptides for the murine microglial cell line, EOC 20, was recognized. A number of
      similar, but not identical, sets of sequences representing more than 75% of all
      the cell line-binding clones were identified. Comparative analysis indicated that
      motif S/(T) F T/(X) Y W is present in the vast majority of the binding sequences.
      The selectivity and specificity of the dominant peptide sequence identified for
      microglia was confirmed using both phage displaying the peptide and the synthetic
      peptide alone.

PMID- 12044971
TI  - Effects of IL6 and IL1beta on aFGF expression and excitotoxicity in NT2N cells.
AB  - The interleukin-1beta (IL1beta) and interleukin-6 (IL6) have pro-inflammatory and
      neuroprotective functions and are elevated in many diseases of the brain. Here,
      mechanisms and effects of IL1beta and IL6 on neuronal survival after excitatory
      stimulation were investigated in vitro. IL6 upregulated the expression of the
      neuroprotective acidic fibroblast growth factor (aFGF) and reduced the glutamate
      induced cytotoxicity. IL1beta treatment amplified the excitotoxic effects after
      24 h, but longer treatment with IL1beta stimulated the neuronal release of IL6
      resulting in increased levels of aFGF and a decreased excitotoxicity. These data
      suggest that (1) IL6 exerts protective functions by upregulating the expression
      of aFGF and (2) the IL6/IL1beta balance in the brain may regulate neuronal
      survival during neuropathological processes.

PMID- 12044972
TI  - Stimulation of chemokine CXC receptor 4 induces synaptic depression of evoked
      parallel fibers inputs onto Purkinje neurons in mouse cerebellum.
AB  - In the present work, we studied the effects of the stimulation of the chemokine
      CXC receptor 4 (CXCR4) by the stromal-derived cell growth factor-1alpha (SDF
      1alpha) on the evoked excitatory postsynaptic current. This was generated in
      Purkinje neurons (PN) from mouse cerebellar slices by the stimulation of parallel
      fibers. It was found that the amplitude of EPSC was reversibly reduced by SDF
      1alpha application. This effect was dose-dependent (IC(50)=0.34 nM) and was
      abolished by the anti-CXCR4 monoclonal antibody (mAb) 12G5. This SDF-1alpha
      induced synaptic depression was caused by a decrease of evoked glutamate release,
      rather than a decrease in the postsynaptic glutamate receptor (GluR) sensitivity,
      as the mean amplitude of the spontaneous EPSCs was not influenced by chemokine
      application. Moreover, NMDA receptors (NMDARs) are involved in EPSC depression
      being inhibited by the NMDAR blocker 2-amino-5-phosphonopentanoic acid (AP-5).
      The mechanisms by which SDF-1alpha modulates neurotransmission in the cerebellar
      cortex are discussed.

PMID- 12044973
TI  - Cobalamin (vitamin B(12)) positively regulates interleukin-6 levels in rat
      cerebrospinal fluid.
AB  - We have previously demonstrated that the repeated intracerebroventricular
      (i.c.v.) microinjection of interleukin-6 (IL-6) prevented the myelinolytic
      lesions of cobalamin-deficient (Cbl-D) central neuropathy [or subacute combined
      degeneration (SCD)] in totally gastrectomized (TGX) rats. We therefore
      hypothesized that cobalamin (Cbl) may actually regulate IL-6 levels in rat
      cerebrospinal fluid (CSF). We measured IL-6 levels in the CSF of rats made Cbl-D
      by means of total gastrectomy (TG) or chronic feeding with a Cbl-D diet and
      killed at different times from the beginning of the experiment, and found that IL
      6 levels significantly and progressively decreased over time. Chronic 2-month Cbl
      administration started 1 week after surgery prevented the decrease in IL-6 levels
      and, when it was started 2 months after surgery, it significantly increased IL-6
      levels, but not to presurgical values. We also investigated whether IL-6 decrease
      might be ultimately due to the Cbl-deficiency-linked decrease in epidermal growth
      factor (EGF) synthesis. Repeated i.c.v. administrations of EGF to TGX rats did
      not modify CSF IL-6 levels. These results, together with those of a previous
      study showing the preventive effect of IL-6 treatment on SCD lesions, demonstrate
      that: (i) Cbl selectively regulates CSF IL-6 levels; and (ii) decreased IL-6
      availability plays a role in the pathogenesis of the experimental SCD, in which
      no evidence of inflammatory and/or immunological reaction has been observed.

PMID- 12044974
TI  - Involvement of noradrenergic nerves in the activation and clonal deletion of T
      cells stimulated by superantigen in vivo.
AB  - Superantigens, like staphylococcal enterotoxin B (SEB), induce a strong
      proliferative response followed by clonal deletion of a substantial portion of
      defined Vbeta T cells. The remaining cells display in vitro anergy. We found that
      the immune response to SEB was paralleled by biphasic changes in the activity of
      the sympathetic nervous system. Furthermore, sympathetic denervation resulted in
      decreased SEB-induced cell proliferation and IL-2 production, and impeded the
      specific deletion of splenic CD4Vbeta8 cells observed in intact animals without
      affecting anergy. These studies provide the first evidence of an immunoregulatory
      cross-talk between sympathetic nerves and superantigen-activated immune cells.

PMID- 12044975
TI  - Generation and characterization of antibodies to sulfated glucuronyl glycolipids
      in Lewis rats.
AB  - Antibodies to sulfated glucuronyl glycolipids (SGGLs) have been reported in sera
      of patients with peripheral neuropathies including patients with IgM gammopathy.
      However, the role of anti-SGGL antibodies in the pathogenesis of neuropathy
      remains unclear. In order to study the role of antibodies to SGGLs in the
      pathogenesis of neuropathy, Lewis female rats were injected with purified SGPG
      mixed with keyhole limpet hemocyanin (KLH) and emulsified with equal amount of
      complete Freund's adjuvant. High titer anti-SGPG antibodies were detected by
      ELISA in sera of all rats inoculated with SGPG. All anti-SGPG antibodies cross
      reacted with human myelin-associated glycoprotein (MAG). None of the sensitized
      rats exhibited clinical signs of neuropathy. Histological examination showed that
      there was no demyelination or axonal damage in peripheral nerves. Our data
      demonstrate that SGPG is a highly immunogenic glycolipid but high titer
      antibodies against it do not produce an experimental autoimmune neuropathy in
      Lewis rats.

PMID- 12044977
TI  - Interferon-beta directly influences monocyte infiltration into the central
      nervous system.
AB  - Interferon-beta (IFN-beta) has beneficial effects on the clinical symptoms of
      multiple sclerosis (MS) patients, but its exact mechanism of action is yet
      unknown. We here suggest that IFN-beta directly modulates inflammatory events at
      the level of cerebral endothelium. IFN-beta treatment resulted in a marked
      reduction of perivascular infiltrates in acute experimental allergic
      encephalomyelitis (EAE), the rat model for MS, which was coupled to a major
      decrease in the expression of the adhesion molecules ICAM-1 and VCAM-1 on brain
      capillaries. In vitro, IFN-beta reduced the mRNA levels and protein expression of
      adhesion molecules of brain endothelial cell cultures and diminished monocyte
      transendothelial migration. Monocyte adhesion and subsequent migration was found
      to be predominantly regulated by VCAM-1. These data indicate that IFN-beta exerts
      direct antiinflammatory effects on brain endothelial cells thereby contributing
      to reduced lesion formation as observed in MS patients.

PMID- 12044976
TI  - Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed
      central nervous system.
AB  - T-cell accumulation in the central nervous system (CNS) is considered crucial to
      the pathogenesis of multiple sclerosis (MS). We found that the majority of T
      cells within the cerebrospinal fluid (CSF) compartment expressed the CXC
      chemokine receptor 3 (CXCR), independent of CNS inflammation. Quantitative
      immunohistochemistry revealed continuous accumulation of CXCR3+ T cells during MS
      lesion formation. The expression of one CXCR3 ligand, interferon (IFN)-gamma
      inducible protein of 10 kDa (IP-10)/CXC chemokine ligand (CXCL) 10 was elevated
      in MS CSF, spatially associated with demyelination in CNS tissue sections and
      correlated tightly with CXCR3 expression. These data suggest a critical role for
      CXCL10 and CXCR3 in the accumulation of T cells in the CNS of MS patients.

PMID- 12044979
TI  - Abrupt or precipitated withdrawal from morphine induces immunosuppression.
AB  - The present studies tested the effect of withdrawal from morphine by two
      different paradigms, abrupt withdrawal (AW) or precipitated withdrawal (PW), on
      the capacity of murine spleen cells to mount an in vitro antibody response. Mice
      were made dependent by chronic treatment using s.c. implanted morphine slow
      release pellets. Splenocytes were harvested at various time points after
      withdrawal and the number of antibody-forming cells determined using a plaque
      forming cell (PFC) assay. The results indicate that induction of abstinence from
      morphine in dependent mice by either paradigm caused marked immunosuppression
      between 24 and 48 h post-withdrawal. However, the kinetics of onset and recovery
      from immunosuppression were different in AW and PW.

PMID- 12044978
TI  - Complement 3 deficiency and oral prednisolone improve strength and prolong
      survival of laminin alpha2-deficient mice.
AB  - Complement deposition and macrophages are common in biopsies of children with
      muscular dystrophy. While the presumed roles of complement and macrophages have
      been those of scavenger to remove and clear necrotic fibers, there is some
      evidence that they play a primary role in the pathogenesis of these diseases.
      Here, we explore the role of complement in the pathogenesis of the most severe
      animal model of congenital dystrophy, the dy-/- mouse, which is laminin alpha2
      deficient. We generated animals deficient in both C3 and laminin alpha2. C3 is
      the third component of the complement cascade and is required for activation of
      either the classical or alternative pathways. Thirty-three percent of the dy-/
      :C3+ mice (n=59) died before 24 weeks while only 14% of the dy-/-:C3-/- (n=29)
      mice died (p=0.04). Absolute forepaw strength was 25-30% greater for the dy-/-:C3
      /- mice up to 20 weeks of age (p<0.05 compared to complement-sufficient). Forepaw
      strength adjusted for weight also showed significant differences with C3-/- mice
      being stronger up to 20 weeks (p<0.05). However, by 24 weeks, the two groups did
      not differ for strength. Next, we treated 20 mice with twice weekly oral
      prednisolone. Survival at 24 weeks for the prednisolone treated dy-/- mice (C3-/-
      or C3+) was 90% (p=0.04). This work shows that complement insufficiency and
      weekly prednisone prolong survival and improve strength of the laminin alpha2
      deficient mouse. This work suggests that the complement system may contribute
      directly to the pathogenesis of this form of dystrophy. Because complement
      activity may be modified pharmacologically, this work may have implications for
      treatment of children with congenital muscular dystrophy secondary to laminin
      alpha2 deficiency.

PMID- 12044980
TI  - Chemokine receptor expression on MBP-reactive T cells: CXCR6 is a marker of
      IFNgamma-producing effector cells.
AB  - Cytokine-polarized T cells have distinct chemokine receptor (CKR) expression
      patterns associated with their cytokine secretion profiles. In order to
      investigate this paradigm in autoreactive human T cells, we have determined the
      CKR expression pattern of myelin basic protein (MBP)-reactive T cell lines (TCL)
      and compared these profiles to those of TCL-generated in response to tetanus
      toxoid (TT). Expression of CXCR6 and CXCR3 on TCL was significantly positively
      correlated with IFNgamma, and inversely correlated with IL-5 production. TT TCL
      had significantly higher expression of CCR7(-)/CD45RA(-) T effector memory (Tem)
      cells than MBP TCL. However, in MBP-specific TCL, CXCR6 was found to be the best
      marker of conversion to the Tem phenotype. CXCR6 and CXCR3 are likely to be
      important in the migration of effector memory T cells in Th1-mediated
      inflammatory diseases such as multiple sclerosis (MS).

PMID- 12044981
TI  - Contribution of T cells to mortality in neurovirulent Sindbis virus
      encephalomyelitis.
AB  - Intranasal inoculation of C57BL/6 mice with a neurovirulent strain of Sindbis
      virus (SV) results in fatal encephalomyelitis. Mice with selective immune
      deficiencies were studied to determine the role of the immune response in fatal
      outcome. Mortality was decreased in mice deficient in alphabeta, but not
      gammadelta, T cells demonstrating a contribution of alphabeta T cells. Mice
      lacking either CD4+ or CD8+ T cells also had reduced mortality and mice lacking
      interferon (IFN)-gamma were completely protected. Clearance of infectious virus
      was identical in mice without T cells or IFN-gamma, but clearance of viral RNA
      was delayed compared to normal mice. Mice unable to produce antibody, perforin,
      Fas, TNF-alpha receptor1, IL-6 or IL-12 were not protected. These data suggest
      that T cells contribute to fatal acute viral encephalomyelitis through the
      production of IFN-gamma.

PMID- 12044982
TI  - Expression of stromal cell-derived factor 1alpha protein in HIV encephalitis.
AB  - Analysis of the patterns of stromal cell-derived factor 1alpha (SDF-1alpha)
      expression in the brains from HIV-positive patients suggests that in neuronal
      cells, SDF-1alpha might play a role in neuroprotection and neurite extension in
      response to HIV infection. In all cases analyzed, SDF-1alpha immunoreactivity was
      primarily present in astroglial cells. Patients with HIV encephalitis (HIVE)
      showed intense somato-dendritic neuronal SDF-1alpha immunoreactivity, while HIVE
      negative patients with neurodegeneration had a significant decrease in neuronal
      SDF-1alpha immunoreactivity. Neuronal cells treated with SDF-1alpha displayed
      increased neurite outgrowth. Similarly, neurons treated with HIV-Tat, which
      induced SDF-1alpha expression, also showed neurite outgrowth. Tat-mediated
      neurite outgrowth was blocked by anti-SDF-1alpha antibody. These results suggest
      that SDF-1alpha may play a role in the neuronal response to HIV in the brains of
      AIDS patients.

PMID- 12044983
TI  - Role of anti-calcium channel and anti-receptor autoantibodies in autonomic
      dysfunction in Sjogren's syndrome.
AB  - Auto-antibodies cross-reacting with L-type voltage-gated calcium channels (VGCCs)
      have been described in primary Sjogren's syndrome (pSS), and may mediate the
      cardiac defects in neonates born to mothers with pSS. L-type VGCCs are also
      present in autonomically innervated tissues. Therefore, the aim of this project
      was to investigate a role for anti-VGCC antibodies and antibodies to alpha(1)
      adrenoceptors or P(2X)-purinoceptors in the autonomic dysfunction that occurs in
      pSS. Contraction of the sympathetically innervated vas deferens in response to
      stimulation of the muscle by an alpha(1)-adrenoceptor agonist (phenylephrine) or
      a P(2X)-purinoceptor agonist (alpha,beta-methylene ATP) was measured in the
      absence and presence of 2% serum. Contractions produced by phenylephrine and by
      alpha,beta-methylene ATP were abolished by nicardipine, demonstrating that they
      are coupled to calcium influx through L-type VGCCs. Serum from patients with pSS
      or from healthy controls did not significantly alter the L-type channel-dependent
      responses of smooth muscle to agonist stimulation. We therefore conclude that pSS
      serum does not contain autoantibodies that functionally inhibit L-type VGCCs,
      alpha(1)-adrenoceptors or P(2X)-purinoceptors in smooth muscle and that such
      autoantibodies cannot explain the autonomic dysfunction in pSS.

PMID- 12044985
TI  - The human nervous tissue in proximity to granulomatous lesions induced by Taenia
      solium metacestodes displays an active response.
AB  - In neurocysticercosis, the nervous tissue surrounding the brain lesion is
      affected as a consequence of the local immune response induced by a Taenia solium
      metacestode. In this study, a histological and immunohistochemical analysis of
      five brain specimens from patients with neurocysticercosis revealed a
      proinflammatory activity reflected by an apparently altered blood-brain barrier
      permeability, secretion of pro-inflammatory cytokines, and up-regulation of
      molecules associated with antigen presentation. There were also anti-inflammatory
      cytokines, as well as an active wound-healing process reflected by angiogenesis,
      collagen deposition and glial scar formation. This immune response displayed by
      the nervous tissue adjacent to chronic neurocysticercosis lesions appeared to be
      contributing to the local tissue damage, and hence, may be fundamental in the
      pathology of NCC.

PMID- 12044984
TI  - Selective matrix metalloproteinase inhibitor, N-biphenyl sulfonyl phenylalanine
      hydroxamic acid, inhibits the migration of CD4+ T lymphocytes in patients with
      HTLV-I-associated myelopathy.
AB  - Matrix metalloproteinases (MMPs) have been reported to be involved in various
      inflammatory disorders. Previous studies revealed that MMP-2 and MMP-9 might play
      important roles in the breakdown of the blood-brain barrier (BBB) in the central
      nervous system (CNS) of patients with HTLV-I-associated myelopathy (HAM)/tropical
      spastic paraparesis (TSP). N-Biphenyl sulfonyl-phenylalanine hydroxamic acid
      (BPHA) selectively inhibits MMP-2, -9 and -14, but not MMP-1, -3 and -7. In the
      present study, we examined whether or not the selective MMP inhibitor BPHA could
      inhibit the heightened migrating activity of CD4+ T cells in HAM/TSP patients.
      The migration assay using an invasion chamber showed that migration of CD4+ T
      cells in HAM/TSP patients was inhibited by 25 microM BPHA. In addition, the
      inhibitory ratio of migrating CD4+ lymphocytes was higher in HAM patients
      compared to normal controls. These results suggest that the selective MMP
      inhibitor BPHA has therapeutic potential for HAM/TSP.

PMID- 12044986
TI  - Ganglioside reactive antibodies in the neuropathy associated with celiac disease.
AB  - We tested patients with celiac disease (CD) for the presence of serum anti
      ganglioside antibodies. Six of twenty-seven patient sera were reactive against
      brain gangliosides by an agglutination immunoassay. Neurological examination in
      all six revealed the presence of distal sensory loss, consistent with the
      diagnosis of peripheral neuropathy. When tested by ELISA for antibodies to
      isolated GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides, all six were positive
      for IgG antibodies to at least one. The neuropathy of celiac disease may be
      autoimmune and associated with anti-ganglioside antibodies. The presence of IgG
      reactivity furthermore implicates a T cell-mediated response to ganglioside
      antigens.

PMID- 12044987
TI  - Short-term dynamics of circulating T cell receptor V beta repertoire in relapsing
      remitting MS.
AB  - To understand the short-term dynamics of the circulating T cell receptor V beta
      (TCRBV) repertoire in relapsing-remitting multiple sclerosis (MS), we monitored
      the TCRBV profiles of untreated MS patients and healthy controls. Expansions of
      TCRBV genes in MS patients were significantly more frequent than in controls
      (P<0.001), were predominantly oligoclonal (80%) and were significantly correlated
      with immune responses to myelin basic protein (MBP) (P<0.02) and with
      inflammatory disease activity detected by magnetic resonance imaging (MRI)
      (P<0.05). Autoreactive T cell responses against myelin antigens may be implicated
      in perturbations of TCR repertoire in untreated MS patients, detectable even in
      the absence of clinically evident manifestations.

PMID- 12044988
TI  - Amyloid-beta-induced chemokine production in primary human macrophages and
      astrocytes.
AB  - In Alzheimer's disease (AD), chemotaxis might be responsible for attracting glial
      cells towards the neuritic plaque. Using primary monocyte-derived macrophages and
      primary adult astrocytes as a model, amyloid-beta (Abeta) (1-42) was able to
      stimulate the production, as measured by RT-PCR, of MIP-1alpha and MIP-1beta mRNA
      in macrophages and MCP-1 in astrocytes. Cocultures showed in unstimulated as well
      as in Abeta-stimulated cells an increase in MIP-1alpha, MIP-1beta and MCP-1 mRNA.
      ELISAs of supernatant samples of stimulated macrophages and astrocytes also
      showed an increase in MIP-1alpha and MIP-1beta in macrophages and MCP-1 in
      astrocytes. Stimulated cocultures showed an increase in MIP-1alpha, MIP-1beta and
      MCP-1 protein levels in contrast to unstimulated cocultures.

PMID- 12044990
TI  - No association of vitamin D-binding protein gene polymorphisms in Japanese
      patients with MS.
AB  - Vitamin D-binding protein (DBP) is known to function as an immunomodulatory
      factor, as well as the main carrier of vitamin D. We analyzed the frequencies of
      two polymorphisms (codon 416 and codon 420) in the DBP gene through a case
      control study involving 107 Japanese patients with multiple sclerosis (MS) and
      109 healthy controls. None of these polymorphisms showed any association with the
      occurrence of MS. Furthermore, no association was observed between the DBP
      polymorphisms and the age at disease onset. These results suggest that DBP does
      not contribute to the development of MS in Japanese.

PMID- 12044989
TI  - Altered cannabinoid receptor mRNA expression in peripheral blood mononuclear
      cells from marijuana smokers.
AB  - We studied, using RT-PCR, the relative expression of cannabinoid receptor (CBR)
      mRNA in peripheral blood mononuclear cells (PBMC) from different donor groups.
      Cells from normal donors expressed a CB2 mRNA level threefold higher than CB1
      across all age, gender or ethnicity groups, and amplicons were of the same size
      in all donors. However, cells from marijuana users expressed higher levels of CBR
      mRNA, but with a preserved CB1/CB2 ratio of 1:3. CBR gene products were also
      studied following short-term mitogen activation in vitro. CB1 expression
      decreased following mitogen stimulation when compared to the time-matched medium
      only cells while the expression of CB2 mRNA remained unchanged. These studies
      suggest that marijuana smoking and immune activation can alter the basal levels
      of CB1 and CB2 in PBMCs.

PMID- 12044997
TI  - Automatic recognition of cortical sulci of the human brain using a congregation
      of neural networks.
AB  - This paper describes a complete system allowing automatic recognition of the main
      sulci of the human cortex. This system relies on a preprocessing of magnetic
      resonance images leading to abstract structural representations of the cortical
      folding patterns. The representation nodes are cortical folds, which are given a
      sulcus name by a contextual pattern recognition method. This method can be
      interpreted as a graph matching approach, which is driven by the minimization of
      a global function made up of local potentials. Each potential is a measure of the
      likelihood of the labelling of a restricted area. This potential is given by a
      multi-layer perceptron trained on a learning database. A base of 26 brains
      manually labelled by a neuroanatomist is used to validate our approach. The whole
      system developed for the right hemisphere is made up of 265 neural networks. The
      mean recognition rate is 86% for the learning base and 76% for a generalization
      base, which is very satisfying considering the current weak understanding of the
      variability of the cortical folding patterns.

PMID- 12044998
TI  - Processing and visualization for diffusion tensor MRI.
AB  - This paper presents processing and visualization techniques for Diffusion Tensor
      Magnetic Resonance Imaging (DT-MRI). In DT-MRI, each voxel is assigned a tensor
      that describes local water diffusion. The geometric nature of diffusion tensors
      enables us to quantitatively characterize the local structure in tissues such as
      bone, muscle, and white matter of the brain. This makes DT-MRI an interesting
      modality for image analysis. In this paper we present a novel analytical solution
      to the Stejskal-Tanner diffusion equation system whereby a dual tensor basis,
      derived from the diffusion sensitizing gradient configuration, eliminates the
      need to solve this equation for each voxel. We further describe decomposition of
      the diffusion tensor based on its symmetrical properties, which in turn describe
      the geometry of the diffusion ellipsoid. A simple anisotropy measure follows
      naturally from this analysis. We describe how the geometry or shape of the tensor
      can be visualized using a coloring scheme based on the derived shape measures. In
      addition, we demonstrate that human brain tensor data when filtered can
      effectively describe macrostructural diffusion, which is important in the
      assessment of fiber-tract organization. We also describe how white matter
      pathways can be monitored with the methods introduced in this paper. DT-MRI
      tractography is useful for demonstrating neural connectivity (in vivo) in healthy
      and diseased brain tissue.

PMID- 12044999
TI  - Fusing speed and phase information for vascular segmentation of phase contrast MR
      angiograms.
AB  - This paper presents a statistical approach to aggregating speed and phase
      (directional) information for vascular segmentation of phase contrast magnetic
      resonance angiograms (PC-MRA). Rather than relying on speed information alone, as
      done by others and in our own work, we demonstrate that including phase
      information as a priori knowledge in a Markov random field (MRF) model can
      improve the quality of segmentation. This is particularly true in the region
      within an aneurysm where there is a heterogeneous intensity pattern and
      significant vascular signal loss. We propose to use a Maxwell-Gaussian mixture
      density to model the background signal distribution and combine this with a
      uniform distribution for modelling vascular signal to give a Maxwell-Gaussian
      uniform (MGU) mixture model of image intensity. The MGU model parameters are
      estimated by the modified expectation-maximisation (EM) algorithm. In addition,
      it is shown that the Maxwell-Gaussian mixture distribution (a) models the
      background signal more accurately than a Maxwell distribution, (b) exhibits a
      better fit to clinical data and (c) gives fewer false positive voxels
      (misclassified vessel voxels) in segmentation. The new segmentation algorithm is
      tested on an aneurysm phantom data set and two clinical data sets. The
      experimental results show that the proposed method can provide a better quality
      of segmentation when both speed and phase information are utilised.

PMID- 12045000
TI  - BrainSuite: an automated cortical surface identification tool.
AB  - We describe a new magnetic resonance (MR) image analysis tool that produces
      cortical surface representations with spherical topology from MR images of the
      human brain. The tool provides a sequence of low-level operations in a single
      package that can produce accurate brain segmentations in clinical time. The tools
      include skull and scalp removal, image nonuniformity compensation, voxel-based
      tissue classification, topological correction, rendering, and editing functions.
      The collection of tools is designed to require minimal user interaction to
      produce cortical representations. In this paper we describe the theory of each
      stage of the cortical surface identification process. We then present
      classification validation results using real and phantom data. We also present a
      study of interoperator variability.

PMID- 12045001
TI  - Nonrigid registration of 3D tensor medical data.
AB  - New medical imaging modalities offering multi-valued data, such as phase contrast
      MRA and diffusion tensor MRI, require general representations for the development
      of automated algorithms. In this paper we propose a unified framework for the
      registration of medical volumetric multi-valued data using local matching. The
      paper extends the usual concept of similarity between two pieces of data to be
      matched, commonly used with scalar (intensity) data, to the general tensor case.
      Our approach to registration is based on a multiresolution scheme, where the
      deformation field estimated in a coarser level is propagated to provide an
      initial deformation in the next finer one. In each level, local matching of areas
      with a high degree of local structure and subsequent interpolation are performed.
      Consequently, we provide an algorithm to assess the amount of structure in
      generic multi-valued data by means of gradient and correlation computations. The
      interpolation step is carried out by means of the Kriging estimator, which
      provides a novel framework for the interpolation of sparse vector fields in
      medical applications. The feasibility of the approach is illustrated by results
      on synthetic and clinical data.

PMID- 12045002
TI  - Automatic detection and segmentation of evolving processes in 3D medical images:
      Application to multiple sclerosis.
AB  - The study of temporal series of medical images can be helpful for physicians to
      perform pertinent diagnoses and to help them in the follow-up of a patient: in
      some diseases, lesions, tumors or anatomical structures vary over time in size,
      position, composition, etc., either because of a natural pathological process or
      under the effect of a drug or a therapy. It is a laborious and subjective task to
      visually and manually analyze such images. Thus the objective of this work was to
      automatically detect regions with apparent local volume variation with a vector
      field operator applied to the local displacement field obtained after a non-rigid
      registration between two successive temporal images. On the other hand,
      quantitative measurements, such as the volume variation of lesions or
      segmentation of evolving lesions, are important. By studying the information of
      apparent shrinking areas in the direct and reverse displacement fields between
      images, we are able to segment evolving lesions. Then we propose a method to
      segment lesions in a whole temporal series of images. In this article we apply
      this approach to automatically detect and segment multiple sclerosis lesions that
      evolve in time series of MRI scans of the brain. At this stage, we have only
      applied the approach to a few experimental cases to demonstrate its potential. A
      clinical validation remains to be done, which will require important additional
      work.

PMID- 12045003
TI  - Cancer gene therapy: 'delivery, delivery, delivery' .
AB  - Gene therapy for cancer treatment represents a promising approach that has shown
      selectivity and efficacy in experimental systems as well as clinical trials. Some
      major problems remain to be solved before this strategy becomes routinely adopted
      in the clinic, one of the main challenges being the improvement of gene delivery.
      Namely, the development of DNA vectors characterized by maximum efficiency and
      minimal toxicity will define the success of gene therapy and its chances of being
      accepted by public and clinicians. A number of issues need to be considered. The
      "magic" vector should be targeted, protected from degradation and immune attack,
      and safe for the recipient and the environment. Moreover, it should express the
      therapeutic gene for as long as required, in an appropriately regulated fashion.
      Vehicles such as retroviruses, adenoviruses and liposomes have been adopted in
      clinical studies, with varying results. New therapeutic modalities are also being
      explored in order to overcome the limitation of poor gene transfer and patient
      toxicity, including bacteria, adeno-associated and herpes simplex viruses,
      lentiviruses, cationic polymer-DNA complexes and electroporation. Some of the
      delivery systems tested in preclinical and clinical models are reviewed in this
      article, with particular attention to the targeting of the tumor environment.

PMID- 12045004
TI  - GnRH and steroids in cancer.
AB  - Gonadotropin-releasing-hormone (GnRH) analogues are synthetic compounds derived
      from decapeptide neurohormones (LHRH; LH/FSH-RH). They have a key role in hormone
      dependent cancer, particularly breast and prostate cancer. GnRH analogues produce
      an efficient inhibition of gonadotropins and sex steroid hormones. Their use in
      cancer therapy result in a, pharmacological castration (i.e. ovariectomy and
      orchiectomy), providing an androgen and estrogen ablation. GnRH exert an
      inhibitory action on the growth of hormone-dependent human and canine mammary
      tumor. Mammary tumors can produce growth factor that potentially could modulate
      their own proliferation in an autocrine fashion (i.e. TGF-alpha and TGF-beta or
      with a paracrine mechanism (i.e. EGF, IGF, FGF). The expression of EGF receptors
      is related in mammary tissues to the action of oestrogen and progesteron and to
      the presence of functional receptors for oestrogen (ER) and progesteron (PR). The
      present review elucidate the role of GnRH receptors in cancer and their
      connection with steroid hormones. Besides we showed the link between GnRH and
      signal transductions pathways: Estrogen-receptors, GnRH-receptors, EGF-receptors
      signal transduction pathways. A very tight link exists between steroid hormones
      and GnRH analogues both on central pituitary gonadal axis and on tumor receptors
      peripherically. This last mechanism could be explained either locally activating
      GnRH receptors or locally interacting with EGF receptor-Intracellular NitricOxide
      system.

PMID- 12045005
TI  - The glycobiology of implantation.
AB  - Embryo implantation involves complex, coordinated interactions of cell surface
      components of embryonic (trophectoderm/trophoblast) and uterine cells.
      Oligosaccharides are common constituents of cell surface molecules. A variety of
      oligosaccharide structures have been identified at embryonic and uterine cell
      surfaces and change dynamically during progression of the implantation reaction.
      In many cases, the oligosaccharides have been shown to have biological activities
      with great relevance to the implantation process. This review summarizes the
      available information on glycoconjugates as it relates to the implantation
      process. It is suggested that carbohydrate bearing molecules at embryonic and
      uterine cell surfaces play diverse roles during the implantation process that are
      similar to the roles suggested for these molecules in other biological contexts.

PMID- 12045007
TI  - Systems analysis of matrix metalloproteinase mRNA expression in skeletal tissues.
AB  - The availability of human genome sequences provides life scientists and
      biomedical engineers with a challenging opportunity to develop computational and
      experimental tools for quantitatively analyzing biological processes. In response
      to a growing need to integrate experimental mRNA expression data with human
      genome sequences, we present here a unique analysis named "Promoter-Based
      Estimation (PROBE)" analysis. The PROBE analysis is "systems analysis" of
      transcriptional processes using control and estimation theories. A linear model
      was built in order to estimate the mRNA levels of a group of genes from their
      regulatory DNA sequences. The model was also used to interpret two independent
      datasets in skeletal tissues. The results demonstrated that the mRNA levels of a
      family of matrix metalloproteinases can be modeled from a distribution of cis
      acting elements on regulatory DNA sequences. The model accurately predicted a
      stimulatory role of cis-acting elements such as AP1, NFY, PEA3, and Sp1 as well
      as an inhibitory role of AP2. These predictions are consistent with biological
      observations, and a specific assay for testing such predictions is proposed.
      Although eukaryotic transcription is a complex mechanism, the two examples
      presented here support the potential use of the described analysis for
      elucidating the functional significance of DNA regulatory elements.

PMID- 12045006
TI  - Chronic alcohol intoxication primes Kupffer cells and endothelial cells for
      enhanced CC-chemokine production and concomitantly suppresses phagocytosis and
      chemotaxis.
AB  - Chemokines are involved in the pathogenesis of alcoholic hepatitis and are
      considered to contribute to the migration of leukocytes into the liver during
      chronic ethanol intoxication. This work tests the hypothesis that chronic ethanol
      consumption selectively enhances chemokine release by Kupffer cells and hepatic
      sinusoidal endothelial cells and migration of inflammatory cells into the liver.
      Furthermore, enhanced hepatic chemokine secretion may induce an autocrine effect
      on the ability of Kupffer cells and endothelial cells to chemotax and ingest
      microbial particles. Male Wistar rats were fed with ethanol in agar block and
      water for 32 weeks, and were allowed free access to solid food. Results show that
      after 32 weeks of feeding, leukocyte infiltration and steatosis were observed in
      the livers of ethanol-fed rats. The majority of the infiltrated cells were CD8+
      cells. Serum ALT, endotoxin, MIP-1alpha, MCP-1 and RANTES, (but not CINC and MIP
      2) were also increased in the ethanol-fed rats than in the pair-fed group.
      Isolated Kupffer cells from ethanol-fed rats were primed for enhanced MIP-1alpha,
      MCP-1, and RANTES production in vitro, while the endothelial cells were primed
      for enhanced MIP-1alpha release only. Chronic alcohol intoxication was also
      associated with increased basal H2O2 formation, enhanced nuclear translocation
      and binding of NF-kappaB, AP-1 and MNP-1 in Kupffer Cells. Chronic ethanol
      feeding significantly enhanced MNP-1 binding, but not those of NF-kappaB and AP-1
      in endothelial cells. Concomitantly, chemokine-induced chemotaxis, E.coli
      phagocytosis and f-met-leu-phe-induced superoxide anion production by Kupffer
      cells were downregulated in the ethanol-fed group. Taken together these data
      demonstrate that prolonged alcohol consumption may compromise the host to
      hepatitis as a result of increased chemokine production and at the same time may
      suppress the innate immune function of hepatic non-parenchymal cells.

PMID- 12045008
TI  - The zebrafish as a model for human disease.
AB  - Much of our current understanding of the function of genes modulating the normal
      process of embryonic development has come from mutant analysis. The availability
      of thousands of mutant lines in zebrafish that allows for identification of novel
      genes regulating various aspects of embryogenesis has been instrumental in
      establishing zebrafish as a robust and reliable genetic system. With the advances
      in genomic sequencing, the construction of several genetic maps, and cloning of
      hundreds of ESTs, positional cloning experiments in zebrafish have become more
      approachable. An increasing number of mutant genes have been cloned. Several
      zebrafish mutants are representative of known forms of human genetic diseases.
      The success of morpholino antisense technology in zebrafish potentially opens the
      door for modeling nearly any inherited developmental defect. This review
      highlights the strengths and limitations of using the zebrafish as an organism
      for elucidation of the genetic etiology of human disease. Additionally a survey
      of current and future zebrafish models of human disease is presented.

PMID- 12045009
TI  - Fungal myocarditis.
AB  - The incidence of invasive fungal disease has dramatically increased over the past
      few decades corresponding to the rising number of immunocompromised patients. The
      major risk factors for severe fungal disease include administration of broad
      spectrum antibiotics, corticosteroids and cytotoxic agents, invasive medical
      procedures, and Human Immunodeficiency Virus (HIV) infection. Invasive fungal
      infections often affect multiple organs, and involvement of the myocardium
      frequently occurs in disseminated disease. Premortem diagnosis of fungal
      myocarditis is difficult since clinical findings of myocardial involvement are
      often absent or ambiguous and blood cultures are often negative. The major fungal
      pathogens responsible for myocardial infection and the clinical settings in which
      they occur are reviewed.

PMID- 12045010
TI  - Molecular pathogenesis of mycoplasma animal respiratory pathogens.
AB  - Mycoplasmas contain the smallest genomes and are the smallest known free-living
      organisms, yet little is known about the molecular details of their pathogenic
      mechanisms. This review focuses on pathogens of production animals, but related
      species colonize and cause disease in humans, fish and other animals, plants and
      insects. The general lack of genetic tools and the inability to apply the few
      that are available to some mycoplasma-host systems has hindered studies of this
      nature. During the last decade, which was characterized by unparalleled advances
      in the understanding of bacterial virulence, studies of mycoplasma pathogenesis
      has languished behind other experimental systems. The one exception has been
      studies on mycoplasma antigenic variation. The explosion of studies in this area
      has been due primarily to the fact that they can be performed in vitro without
      genetic tools and with simple well developed biochemical approaches. Not
      withstanding that antigenic variation may play an important role in disease,
      there have been few studies establishing the importance of this phenomenon in
      vivo for a variety of reasons. The same is true for cell invasion as it has been
      defined in cell culture systems, which if it occurs in vivo may change the way we
      think about mycoplasma disease. These advances give insight to an extraordinary
      group of organisms that interact with their hosts in unique and intriguing ways.

PMID- 12045011
TI  - Animal models of ultraviolet radiation (UVR)-induced cutaneous melanoma.
AB  - The incidence of cutaneous melanoma continues to increase in many parts of the
      world including the United States. The American Cancer Society predicts that
      there will be approximately 53,600 new cases of melanoma in the United States
      during 2002 and that there will be 7,400 deaths from melanoma during the same
      time period. Increased understanding of the underlying mechanisms and risk
      factors involved in the induction of this deadly disease will require the use of
      suitable animal models of melanoma. To date, the induction of cutaneous melanoma
      with ultraviolet radiation (UVR) alone has been observed only in a few diverse
      animal models: a South American opossum, Monodelphis domestica; a hybrid fish,
      Xiphophorus; several stocks of transgenic mice; and in Angora goats. Most of
      these models are not completely suitable due to: 1) the target cell for melanoma
      formation; 2) the location of the melanocytes in the skin (i.e.- dermal as
      opposed to epidermal in humans); or 3) problems associated with husbandry and
      experimental manipulation. Recent studies have identified a mouse, the hepatocyte
      growth factor/scatter factor (HGF/SF) transgenic mouse, as an attractive model
      with which to study the induction of melanoma following a single, neonatal
      exposure to a moderate dose of UVR.

PMID- 12045012
TI  - Association of alcohol consumption and exaggerated immunopathologic effects in
      the liver induced by infectious organism.
AB  - The cause of alcoholic liver disease (ALD) is multifactorial and poorly
      understood. It is clear that alcohol alone is not responsible for most of the
      changes associated with ALD and that cofactors are involved in initiation and
      production of ALD. One cofactor that has received a great deal of attention
      recently is the concomitant infection with hepatitis C virus (HCV) and alcohol
      abuse. The interactive effects of HCV and alcohol abuse are still unclear, but
      apparently they are the result of an inability of the immune system to control
      the viral infection and exaggerated hepatocyte damage mediated by either the
      cells of the inflammatory response or factors produced by the inflammatory cells.
      A major effort in my laboratory has been focused on defining the effects of
      alcohol consumption on immunity to various infectious agents. Efforts have also
      been directed to elucidating the pathologic effects in the liver of inflammatory
      and immune responses to microorganisms that either specifically or ultimately
      infect the liver from an initial site of infection other than the liver. This
      review will focus on one aspect of the possible pathogenic effects associated
      with alcohol abuse and hepatic infections: the possible role of the immune
      system, notably the cytotoxic T lymphocyte (CTL) response. It is clear that the
      development of a CTL response is critical for the control of HCV and other
      infections, and it is also likely that this response is involved in liver damage.
      In this review, the evidence that shows the importance of the CD8+ CTL in
      bacterial and viral clearance and the role for pathogenesis will be presented.
      Findings obtained from animal studies that support the suggestion that activated
      CD8+ CTLs can induce liver damage will be presented, as will results of recent
      studies from my laboratory that provide evidence for an effect of alcohol to
      enhance the liver damage mediated by activated CD8+ T cells.

PMID- 12045013
TI  - Mechanisms of human cytomegalovirus persistence and latency.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous beta-herpesvirus that causes severe
      disease primarily in immunosuppressed individuals. A major characteristic of HCMV
      with obvious clinical importance is the ability of the virus to establish
      lifelong infection within the host following the initial acute infection. One
      strategy used by HCMV to maintain itself within the host is the establishment of
      cellular sites of persistent infection and viral latency. Recent studies have
      identified endothelial cells and monocyte-derived macrophages (MDM) as sites of
      HCMV persistence and latency. These studies show that endothelial cell origin and
      MDM differentiation pathway are critical factors that influence the
      characteristics of HCMV replication in these cell types. The specific HCMV genes
      involved in endothelial cell and MDM tropism are unknown. However, studies in the
      closely related murine cytomegalovirus (MCMV) model have provided considerable
      insight into viral genes that enable replication in these cell types. This review
      will focus on mechanisms of HCMV replication in endothelial cells and MDM, and on
      the viral genes involved in regulation of viral replication in these important
      cell types.

PMID- 12045014
TI  - Regulation of sarcoplasmic reticulum calcium release by luminal calcium in
      cardiac muscle.
AB  - The amount of Ca2+ released from the sarcoplasmic reticulum (SR) is a principal
      determinant of cardiac contractility. Normally, the SR Ca2+ stores are mobilized
      through the mechanism of Ca2+-induced Ca2+ release (CICR). In this process, Ca2+
      enters the cell through plasmalemmal voltage-dependent Ca2+ channels to activate
      the Ca2+ release channels in the SR membrane. Consequently, the control of Ca2+
      release by cytosolic Ca2+ has traditionally been the main focus of cardiac
      excitation-contraction (EC) coupling research. Evidence obtained recently
      suggests that SR Ca release is controlled not only by cytosolic Ca2+, but also by
      Ca2+ in the lumen of the SR. The presence of a luminal Ca2+ sensor regulating
      release of SR luminal Ca2+ potentially has profound implications for our
      understanding of EC coupling and intracellular Ca2+ cycling. Here we review
      evidence, obtained using in situ and in vitro approaches, in support of such a
      luminal Ca2+ sensor in cardiac muscle. We also discuss the role of control of
      Ca2+ release channels by luminal Ca2+ in termination and stabilization of CICR,
      as well as in shaping the response of cardiac myocytes to various inotropic
      influences and diseased states such as Ca2+ overload and heart failure.

PMID- 12045015
TI  - Physical variables in experimental photocarcinogenesis and quantitative
      relationships between stages of tumor development.
AB  - Solar ultraviolet (UV) radiation is a prominent environmental carcinogen, but it
      does not penetrate any deeper than the skin. The UV-related skin cancers are by
      far the most common form of cancer among white Caucasians in the USA and
      Australia, and this poses a serious public health problem. Chronic UV exposure of
      hairless mice is a well established model for squamous cell carcinomas in man. It
      is important to identify the essential physical variables, and explore fully how
      photocarcinogenesis evolves in dependence of these variables. The 3 main physical
      variables in photocarcinogenesis are (i) the wavelength of the radiation, (ii)
      the exposure and (iii) time. A good quantitative description of tumor induction
      and precursing stages can be given in terms of these variables. An analysis of
      this description shows us that the early induction of clusters of epidermal cells
      that over-express mutant p53 ('p53 patches') are closely and, most likely,
      causally linked to the eventual tumors. These p53 patches may thus serve as early
      indicators of tumor risk. The induction of an immune-tolerance toward the UV
      induced tumors precedes the actual occurrence of the tumors at high daily doses,
      but extrapolation indicates that this order of events may be reversed at low
      daily doses. This disparity between the dose-time relationships for the tumor
      tolerance and the tumors needs to be investigated further. It could imply a shift
      to non-immunogenic tumors at low daily doses.

PMID- 12045016
TI  - Three-dimensional reconstruction of ryanodine receptors.
AB  - Nearly all available information on the three-dimensional structure of the
      ryanodine receptor (RyR) class of intracellular calcium release channels has come
      from electron microscopy. This review focuses on results that have been obtained
      by cryo-electron microscopy of purified, detergent-solubilized receptors in
      combination with single-particle image processing. This approach has led to the
      most detailed 3D models of RyRs, which are currently at resolutions of 20-30  .
      All three of the known genetic isoforms show essentially identical architectures
      at this resolution: a large, 4-fold symmetric, cytoplasmic assembly that accounts
      for greater than 80% of the receptor's mass and is composed of at least 10
      discrete, loosely packed domains, and a transmembrane region whose dimensions
      lead us to conclude that very little of RyR's protein mass is present on the
      lumenal side of the sarco/endoplasmic reticulum. Three-dimensional
      reconstructions determined for RyRs that have been exposed to conditions that
      promote either open or closed states show subtle differences, some of which are
      located in the cytoplasmic assembly, at sites more distant than 100   from the
      ion channel in the transmembrane region. Several of the ligands (FK506-binding
      protein, calmodulin, dihydropyridine receptor) that interact in vivo with the
      skeletal RyR have been, or are in the process of being, mapped to various
      locations on the cytoplasmic assembly.

PMID- 12045017
TI  - Endometrial cell specific gene activation during implantation and early
      pregnancy.
AB  - Human endometrium expresses numerous genes to achieve an optimal uterine
      environment for implantation and maintaining the pregnancy. In this review, we
      will summarize our previous observations on progestin regulated gene expression,
      estrogen metabolic enzymes, nitric oxide synthase, aromatase, IGF-I and II, IGFBP
      1, prolactin and glycodelin. These genes are differentially activated in two
      types of endometrial cells during the menstrual cycle and early pregnancy.
      Multiple gene activation driven by progestin appears to be the major event
      responsible for the differentiation of endometrial cells. They play critical
      roles of endometrial cell function during implantation and pregnancy.

PMID- 12045018
TI  - The modulation of macrophage activation by tyrosine phosphorylation.
AB  - Activated macrophages are a critical component of our antimicrobial
      armamentarium. Unfortunately, the lipid mediators and free radicals that these
      cells produce are not only toxic to potential pathogens, but also to the host.
      Thus the modulation of these activities can mitigate an overzealous immune
      response and thereby prevent host cell injury. Two families of receptor tyrosine
      kinases (RTK) in macrophages, the RON/STK and the Tyro3 families of protein
      kinases, will be examined in this review with an emphasis on their roles in
      modulating the effector functions of activated macrophages. Both families of
      receptors are capable of down-regulating the inflammatory response of macrophages
      to lipopolysaccharide, and both families of RTK's are structurally related. An
      analysis of the intracellular domains of RON/STK and Tyro3 reveal a common multi
      substrate binding site, which can recruit common signaling molecules such as
      growth factor receptor bound 2 (Grb2) and phosphatidylinositol 3-kinase (PI3-K).
      The observations relating to a modulation of macrophage effector mechanisms by
      these receptors open unexplored avenues for the development of pharmacological
      immunomodulators with the potential to exploit elements of this common pathway.

PMID- 12045019
TI  - Calmodulin modulation of proteins involved in excitation-contraction coupling.
AB  - Muscle excitation-contraction coupling is, in large part, regulated by the
      activity of two proteins. These are the ryanodine receptor (RyR), which is an
      intracellular Ca2+ release channel and the dihydropyridine receptor (DHPR), which
      is a voltage gated L-type calcium channel. In skeletal muscle, the physical
      association between RyR1 and L-type Ca2+ channels is required for muscle
      excitation-contraction coupling. RyRs also regulate intracellular Ca2+
      homeostasis, thereby contributing to a variety of cellular functions in different
      tissues. A wide variety of modulators directly regulate RyR1 activity and,
      consequentially, alter both excitation-contraction coupling and calcium
      homeostasis. Calmodulin, one of these cellular modulators, is a ubiquitously
      expressed 17 kDa Ca2+ binding protein containing four E-F hands, which binds to
      RyR1 at both nanomolar and micromolar Ca2+ concentrations. Apocalmodulin (Ca2+
      free calmodulin) is a partial agonist, while Ca2+calmodulin is an inhibitor of
      RyR1. This conversion of calmodulin from an activator to an inhibitor is due to
      Ca2+ binding to the two C-terminal sites on calmodulin. Calmodulin can also
      modulate the L-type Ca2+ channel in the transverse tubule membrane, producing
      either inactivation or facilitation of the channel upon elevation of the local
      Ca2+ concentrations. Calmodulin binds to a region on RyR1 corresponding to amino
      acids 3614-3643 and to a region in the carboxy-terminal tail of the L-type Ca2+
      channel (1 subunit. However, these calmodulin binding motifs on both proteins
      bind to undetermined motifs on the other protein, suggesting that they represent
      more general protein-protein interaction motifs. These findings raise questions
      about the role of calmodulin in excitation-contraction coupling in skeletal
      muscle.

PMID- 12045020
TI  - Decoding implantation and menstruation: the tale of two opposing signals.
AB  - Human endometrium is a unique tissue that undergoes sequential phases of
      proliferation, and secretory changes followed by tissue shedding and bleeding
      during menstruation. Tissue remodeling is a distinct feature of human endometrium
      in the secretory phase which prepares endometrium for implantation during the
      "receptive phase" of the cycle. A discrete dissolution of extracellular matrix
      (ECM) by a host of enzymes called matrix metalloproteases (MMP) is required for a
      successful implantation. In the absence of implantation, as a result of
      progesterone withdrawal, human endometrium loses its receptive state in the
      premenstrual period and subsequently undergoes a generalized breakdown of ECM by
      MMPs during menstruation. The homeostasis of ECM of endometrium and the delicate
      balance between its synthesis and degradation appear to be mediated by reciprocal
      interaction between TGF-beta and ebaf (lefty) signaling. While TGF-beta acts as a
      pro-fibrogenic cytokine and maintains the integrity of ECM in endometrium,
      expression of lefty is associated with events that lead to destruction of ECM
      facilitating tissue shedding.

PMID- 12045021
TI  - Progesterone receptors and Sp/Kruppel-like family members in the uterine
      endometrium .
AB  - Sp/KLF family members, of which at least 20 distinct nuclear proteins are known
      to date, serve as transcription factors by binding to GC-enriched sites within
      target gene promoters. These molecules regulate diverse cellular processes such
      as proliferation, differentiation, and apoptosis, via their interactions with
      various other nuclear proteins in promoter- and cell-context-dependent pathways
      to effect transactivation or transrepression. Recent studies indicate that Sp
      family members may functionally interact with ligand-activated nuclear receptors,
      especially those for steroid hormones. This review provides a discussion of the
      putative mechanisms and important participants involved in the crosstalk between
      selected members of this family and the receptor for the pregnancy hormone
      progesterone, and the relevant outcomes to the control of the transcriptional
      network in the uterine endometrium.

PMID- 12045022
TI  - The motor efficacy of the artificial colonic pacemaker in colonic inertia
      patients.
AB  - We have recently demonstrated that the colon possesses at least 4 pacemakers
      which presumably generate electric waves and that colonic pacing evokes electric
      activity in colonic inertia. We tested the hypothesis that electric waves
      produced by artificial colonic pacing in colonic inertia patients may initiate
      colonic motilitiy and effect evacuation. 17 patients with constipation due to
      total colonic inertia were divided into 2 groups: 10 (age 45.6 ( 6.3 years, 7
      women) in the study group and 7 (age 43.7 ( 5.8 years, 5 women) as controls. 7
      healthy volunteers were included in the study. Colonic pacing was tested at 2
      sites of pacemakers: mid-transverse colon and colosigmoid junction. A stimulating
      electrode was hooked to the colonic mucosa at the pacemaker site and 2-3
      recording electrodes distally to it. Healthy volunteers showed resting electric
      waves in the form of pacesetter and action potentials which increased
      significantly on colonic pacing. Inertia patients exhibited no basal electric
      activity. Colonic pacing in the study group evoked electric waves and caused
      expulsion of small volume balloon. Balloon distension at pacemaker site produced
      mass movement of balloon, while away from pacemaker site step-wise movement. In
      conclusion, colonic pacing evoked electric waves in colonic inertia patients and
      effected balloon expulsion. We postulate that the pacemaker generates electric
      waves which spread along pacemaker branches that are composed of interstitial
      cells of Cajal and nerve fibers of the enteric nervous plexus and effect colonic
      mass contraction. Ex-pacemaker stimulation presumably leads to local activation
      of interstitial cells of Cajal and segmental step-wise contraction.

PMID- 12045023
TI  - Progesterone and the control of uterine cell proliferation and differentiation.
AB  - Progesterone is the only steroid hormone that is essential for the establishment
      and maintenance of pregnancy in all mammalian species that have been studied.
      Mice lacking the progesterone receptor (PR) by targeted mutagenesis exhibit
      abnormalities in all aspects of reproduction including sexual behavior, mammary
      gland development, ovulation, and implantation. Implantation in PR null mice
      fails, in part, because the uterine stromal cells cannot undergo differentiation
      (the decidual cell reaction). Uterine stromal cells do not divide without
      progesterone and proliferation is blocked by progesterone antibodies and PR
      antagonism. In spite of the preeminence of progesterone in female reproduction,
      its molecular mechanisms of action on target cell proliferation and
      differentiation are not well understood. Recent studies suggest that progesterone
      plays a direct role in regulating cell cycle transit by increasing the expression
      and activation of cell cycle regulatory complexes. Furthermore, this progesterone
      dependent regulation of cell cycle transit may provide a unique window of
      opportunity for uterine stromal cells to exit the proliferative cycle, and if
      exposed to appropriate agents, enter into the differentiation pathway.

PMID- 12045024
TI  - Age- and size-related trends in woody plant shoot development: regulatory
      pathways and evidence for genetic control.
AB  - Woody plants exhibit significant and predictable patterns of change in morphology
      and physiology as they become older and larger. Four models of potential pathways
      controlling these changes are presented: a stimulus-response model in which fully
      developed organs respond to changes in environment (defined here as everything
      external to the organ); an extrinsic model in which the attributes of developing
      organs are determined by environmental factors; an intrinsic model in which
      changes are a result of programmed changes in gene expression; and an extrinsic
      intrinsic model in which changes in gene expression are induced by environmental
      factors. We review evidence that a genetic component is involved in controlling
      age- and size-related changes in foliar morphology and physiology and discuss the
      possibility of complex interactions among model pathways.

PMID- 12045025
TI  - Stomatal conductance alone does not explain the decline in foliar photosynthetic
      rates with increasing tree age and size in Picea abies and Pinus sylvestris.
AB  - Foliar light-saturated net assimilation rates (A) generally decrease with
      increasing tree height (H) and tree age (Y), but it is unclear whether the
      decline in A is attributable to size- and age-related modifications in foliage
      morphology (needle dry mass per unit projected area; M(A)), nitrogen
      concentration, stomatal conductance to water vapor (G), or biochemical foliage
      potentials for photosynthesis (maximum carboxylase activity of Rubisco; V(cmax)).
      I studied the influences of H and Y on foliage structure and function in a data
      set consisting of 114 published studies reporting observations on more than 200
      specimens of various height and age of Picea abies (L.) Karst. and Pinus
      sylvestris L. In this data set, foliar nitrogen concentrations were independent
      of H and Y, but net assimilation rates per unit needle dry mass (A(M)) decreased
      strongly with increasing H and Y. Although M(A) scaled positively with H and Y,
      net assimilation rates per unit area (A(A) = M(A) x A(M)) were strongly and
      negatively related to H, indicating that the structural adjustment of needles did
      not compensate for the decline in mass-based needle photosynthetic rates. A
      relevant determinant of tree height- and age-dependent modifications of A was the
      decrease in G. This led to lower needle intercellular CO2 concentrations and
      thereby to lower efficiency with which the biochemical photosynthetic apparatus
      functioned. However, V(cmax) per unit needle dry mass and area strongly decreased
      with increasing H, indicating that foliar photosynthetic potentials were lower in
      larger trees at a common intercellular CO2 concentration. Given the constancy of
      foliar nitrogen concentrations, but the large decline in apparent V(cmax) with
      tree size and age, I hypothesize that the decline in Vcmax results from
      increasing diffusive resistances between the needle intercellular air space and
      carboxylation sites in chloroplasts. Increased diffusive limitations may be the
      inevitable consequence of morphological adaptation (changes in M(A) and needle
      density) to greater water stress in needles of larger trees. Foliage structural
      and physiological variables were nonlinearly related to H and Y, possibly because
      of hyperbolic decreases in shoot hydraulic conductances with increasing tree
      height and age. Although H and Y were correlated, foliar characteristics were
      generally more strongly related to H than to Y, suggesting that increases in
      height rather than age are responsible for declines in foliar net assimilation
      capacities.

PMID- 12045026
TI  - Comparing the influence of site quality, stand age, fire and climate on
      aboveground tree production in Siberian Scots pine forests.
AB  - Temporal patterns of stem and needle production and total aboveground net primary
      production (ANPP) were studied at the tree and stand level along four
      chronosequences of Siberian Scots pine (Pinus sylvestris L.) forests differing in
      site quality (poor lichen type or the more fertile Vaccinium type) and in
      frequency of surface fires (unburned, moderately burned (fire return interval of
      approximately 40 years), or heavily burned (fire return interval of approximately
      25 years)). The maximum range of variability in aboveground production was
      quantified for: (1) possible long-term changes in site quality; (2) stand age;
      (3) non-stand-replacing, recurring surface fires; and (4) interannual climate
      variability. For (1) and (2), total ANPP was low in the lichen-type
      chronosequence, reached a maximum of 170 g C m(-2) year(-1) after 100 years and
      decreased to 100 g C m(-2) year(-1) in older stands. Maximum ANPP in the
      Vaccinium-type chronosequence was 340 g C m(-2) year(-1) and occurred earlier in
      the 53-year-old stand than in the other stands. Along the lichen-type
      chronosequences, peak ANPP was paralleled by maximum carbon allocation to stem
      growth. (3) In mature trees, damage by recurrent surface fires decreased stem
      growth by 17 +/- 19% over a 10-year period relative to pre-fire values. At longer
      timescales, ANPP was hardly affected by fire-related differences in mortality.
      (4) Needle- plus stem-NPP, reconstructed for a 3-year period, varied within a
      range of 15 g C m(-2) year(-1) in the lichen-type stands and 35 g C m(-2) year(
      1) in the Vaccinium-type stands. For the same period, the coefficient of variance
      was higher for needle-NPP (20 +/- 10%) than for stem-NPP (12 +/- 7%). Needle- and
      stem-NPP did not covary in time. Most 30-year time series of stem-NPP at the tree
      level exhibited strong autocorrelation. In older trees, stem-NPP was positively
      correlated with growing season precipitation. Thus, the factors driving
      variability in ANPP ranked according to their maximum influence as: stand age
      (controlled by the frequency of stand-replacing fires) > site quality > growth
      depression because of surface fire damage approximately equal age-related
      reduction in ANPP > interannual variability approximately equal long-term effects
      of fire (stand density reduction). In lichen-type forests, we found that ANPP at
      the landscape level declined sharply when the interval between stand-replacing
      fires was less than 120 years, illustrating that fire strongly influences ANPP of
      boreal Scots pine forests.

PMID- 12045027
TI  - Hydraulic constraints in the functional scaling of trees.
AB  - I conducted a literature survey to assess the available information on
      relationships between size--expressed in terms of diameter and dry biomass--and
      hydraulic efficiency of woody structures at different scales, from stem segments
      to whole trees. Three data sets were constructed: the first described the
      relationship between segment diameter and hydraulic conductivity (k(h); kg m s(
      1) MPa(-1)) in four species; the second, for the same four species, described the
      intraspecific trajectories of change in total hydraulic conductance (G; kg s(-1)
      MPa(-1)) during ontogeny, i.e., from saplings to mature trees, thereby providing
      a comparison between allometric scaling laws at the scales of segments and whole
      trees; the third comprised pooled means for nine species that described the
      interspecific trajectory of change in G with tree size. The scaling coefficients
      obtained were compared with predictions made with an architectural fractal-like
      model incorporating tissue-specific hydraulic architecture parameters (West et
      al. 1999). When data on segment k(h) were examined, the fractal-like model
      closely predicted the scaling of k(h) with segment diameter in four species.
      However, the model failed to predict accurately in all species the intraspecific
      scaling at the branch and whole-tree levels, and consistently overestimated the
      scaling coefficients. The results suggest that ontogenetic changes in tree size
      during the life cycle of one tree may result in tradeoffs between optimal
      hydraulic supply to the existing leaf area and maintenance costs of the
      supporting xylem tissue. The model of West et al. (1999) may be useful for
      understanding broad interspecific patterns, but not for understanding more subtle
      ontogenetic changes.

PMID- 12045028
TI  - Age-related effects on leaf area/sapwood area relationships, canopy transpiration
      and carbon gain of Norway spruce stands (Picea abies) in the Fichtelgebirge,
      Germany.
AB  - Stand age is an important structural determinant of canopy transpiration (E(c))
      and carbon gain. Another more functional parameter of forest structure is the
      leaf area/sapwood area relationship, A(L)/A(S), which changes with site
      conditions and has been used to estimate leaf area index of forest canopies. The
      interpretation of age-related changes in A(L)/A(S) and the question of how
      A(L)/A(S) is related to forest functions are of current interest because they may
      help to explain forest canopy fluxes and growth. We conducted studies in mature
      stands of Picea abies (L.) Karst. varying in age from 40 to 140 years, in tree
      density from 1680 to 320 trees ha(-1), and in tree height from 15 to 30 m.
      Structural parameters were measured by biomass harvests of individual trees and
      stand biometry. We estimated E(c) from scaled-up xylem sap flux of trees, and
      canopy-level fluxes were predicted by a three-dimensional microclimate and gas
      exchange model (STANDFLUX). In contrast to pine species, A(L)/A(S) of P. abies
      increased with stand age from 0.26 to 0.48 m(2) cm(-2). Agreement between E(c)
      derived from scaled-up sap flux and modeled canopy transpiration was obtained
      with the same parameterization of needle physiology independent of stand age.
      Reduced light interception per leaf area and, as a consequence, reductions in net
      canopy photosynthesis (A(c)), canopy conductance (g(c)) and E(c) were predicted
      by the model in the older stands. Seasonal water-use efficiency (WUE =
      A(c)/E(c)), derived from scaled-up sap flux and stem growth as well as from model
      simulation, declined with increasing A(L)/A(S) and stand age. Based on the
      different behavior of age-related A(L)/A(S) in Norway spruce stands compared with
      other tree species, we conclude that WUE rather than A(L)/A(S) could represent a
      common age-related property of all species. We also conclude that, in addition to
      hydraulic limitations reducing carbon gain in old stands, a functional change in
      A(L)/A(S) that is related to reduced light interception per leaf area provides
      another potential explanation for reduced carbon gain in old stands of P. abies,
      even when hydraulic constraints increase in response to changes in canopy
      architecture and aging.

PMID- 12045029
TI  - Effects of branch height on leaf gas exchange, branch hydraulic conductance and
      branch sap flux in open-grown ponderosa pine.
AB  - Recent studies have shown that stomata respond to changes in hydraulic
      conductance of the flow path from soil to leaf. In open-grown tall trees,
      branches of different heights may have different hydraulic conductances because
      of differences in path length and growth. We determined if leaf gas exchange,
      branch sap flux, leaf specific hydraulic conductance, foliar carbon isotope
      composition (delta13C) and ratios of leaf area to sapwood area within branches
      were dependent on branch height (10 and 25 m) within the crowns of four open
      grown ponderosa pine (Pinus ponderosa Laws.) trees. We found no difference in
      leaf gas exchange or leaf specific hydraulic conductance from soil to leaf
      between the upper and lower canopy of our study trees. Branch sap flux per unit
      leaf area and per unit sapwood area did not differ between the 10- and 25-m
      canopy positions; however, branch sap flux per unit sapwood area at the 25-m
      position had consistently lower values. Branches at the 25-m canopy position had
      lower leaf to sapwood area ratios (0.17 m2 cm-2) compared with branches at the 10
      m position (0.27 m2 cm-2) (P = 0.03). Leaf specific conductance of branches in
      the upper crown did not differ from that in the lower crown. Other studies at our
      site indicate lower hydraulic conductance, sap flux, whole-tree canopy
      conductance and photosynthesis in old trees compared with young trees. This study
      suggests that height alone may not explain these differences.

PMID- 12045030
TI  - Age effects on Norway spruce (Picea abies) susceptibility to ozone uptake: a
      novel approach relating stress avoidance to defense.
AB  - Cumulative ozone (O3) uptake and O3 flux were related to physiological,
      morphological and biochemical characteristics of Norway spruce (Picea abies (L.)
      Karst.) trees of different ages. Under ambient CO2 conditions, photosynthetic
      capacity (Amax) declined in mature trees when cumulative O3 uptake into needles,
      which provides a measure of effective O3 dose, exceeded 21 mmol m-2 of total
      needle surface area. A comparable decline in Amax of seedlings occurred when
      cumulative O(3) uptake was only 4.5 mmol m-2. The threshold O3 flux causing a
      significant decline in Amax ranged between 2.14 and 2.45 nmol m-2 s-1 in mature
      trees and seedlings subjected to exposure periods of > or = 70 and > or = 23
      days, respectively. The greater O3 sensitivity of young trees compared with
      mature trees was associated with needle morphology. Biomass of a 100-needle
      sample increased significantly with tree age, whereas a negative correlation was
      found for specific leaf area, these changes parallel those observed during
      differentiation from shade-type to sun-type needles with tree ontogeny. Age
      dependent changes in leaf morphology were related to changes in detoxification
      capacity, with area-based concentrations of ascorbate increasing during tree
      ontogeny. These findings indicate that the extent of O3-induced injury is related
      to the ratio of potentially available antioxidants to O3 influx. Because this
      ratio, when calculated for ascorbate, increased with tree age, we conclude that
      the ratio may serve as an empirical basis for characterizing age-related
      differences in tree responses to O3.

PMID- 12045031
TI  - Tree- and needle-age-dependent variations in antioxidants and photoprotective
      pigments in Norway spruce needles at the alpine timberline.
AB  - To cope with environmental stress, plants are equipped with antioxidative (e.g.,
      ascorbate, glutathione and alpha-tocopherol) and photoprotective (e.g.,
      xanthophyll cycle pigments) defense systems. We investigated the defense
      capacities of three tree age classes (mature, sapling and seedling) of Norway
      spruce (Picea abies (L.) Karst.) at a field site near the timberline. Biochemical
      data were expressed on both a needle dry mass and a surface area basis. Compared
      with current-year needles, previous-year needles contained higher mass- and area
      based concentrations of chlorophylls and alpha-tocopherol, and a larger
      xanthophyll cycle pool that was in a more epoxidized state. Total glutathione
      concentration was lower, the glutathione pool was more reduced and the ascorbate
      pool was more oxidized in previous-year needles than in current-year needles.
      Needle concentrations of glutathione and alpha-tocopherol increased and
      chlorophyll concentration decreased with increasing tree age when expressed on a
      surface area basis. On a dry mass basis, these trends were reversed or
      nonexistent. The ascorbate pool was more reduced and the glutathione pool was
      more oxidized in needles of mature trees than in needles of saplings and
      seedlings. The proportion of protective xanthophyll cycle pigments decreased and
      the de-epoxidation state increased with increasing tree age. We conclude that
      tree age and the basis of expression of antioxidant concentration--surface area
      or dry mass--are important in scaling from seedlings to large trees.

PMID- 12045032
TI  - Reduced photosynthesis in old oak (Quercus robur): the impact of crown and
      hydraulic architecture.
AB  - We tested the hypothesis that changes in crown architecture of old pedunculate
      oak trees (Quercus robur L. ssp. robur Kl. et Kr. et Rol.) reduce leaf specific
      hydraulic conductance of shoots, thereby limiting stomatal conductance and
      assimilation of affected shoots. At the end of summer 1999, hydraulic conductance
      and leaf specific hydraulic conductance, measured with a high-pressure flow meter
      in 0.5- to 1.5-m long shoots, were 27 and 39% lower, respectively, in shoots of
      low vigor compared with vigorously growing shoots in a 165-year- old stand in
      southeastern Germany. Two types of bottlenecks to water transport can be
      identified in shoots of old oak trees, namely nodes and abscission zones. The
      reduction in hydraulic conductance was especially severe in shoots with diameters
      of less than 2 mm. Maximum stomatal conductance and maximum net assimilation rate
      increased significantly with hydraulic conductance and leaf specific hydraulic
      conductance. Our data support the hypothesis that changes in shoot and
      consequently crown architecture observed in aging trees can limit photosynthesis
      by reducing shoot hydraulic conductance. Thus, in addition to increasing pathway
      length and lower conductivity of xylem in old trees, structural changes in shoot
      and crown architecture need to be considered when analyzing water relations and
      photosynthesis in mature and declining trees.

PMID- 12045033
TI  - ICG-assisted peeling of the retinal ILM.

PMID- 12045034
TI  - ICG-assisted peeling of the retinal ILM.

PMID- 12045036
TI  - ICG-assisted peeling of the retinal ILM.

PMID- 12045037
TI  - "Not quite" natural history of NTG.

PMID- 12045038
TI  - Corneal flap thickness and tissue laser ablation in myopic LASIK.

PMID- 12045040
TI  - Verteporfin in Photodynamic Therapy (VIP) Study group.

PMID- 12045041
TI  - Learning from surgical failures: an argument for clinical trials.

PMID- 12045042
TI  - Five-year incidence of open-angle glaucoma: the visual impairment project.
AB  - PURPOSE: To determine the incidence of open-angle glaucoma (OAG) in Melbourne,
      Victoria, Australia. DESIGN: Population-based cohort study. PARTICIPANTS: Total
      of 3271 participants aged 40 years and older from Melbourne, Victoria, Australia.
      MAIN OUTCOME MEASURES: Five-year incidence of OAG. METHODS: Participants were
      recruited through a cluster random sampling from nine urban clusters. Baseline
      examination was conducted from 1992 through 1994, and the follow-up data were
      collected from 1997 through 1999. Each participant both at baseline and follow-up
      underwent a standardized ophthalmic examination including intraocular pressure
      measurement, visual field assessment, cup-to-disc ratio measurement, and paired
      stereo photographs of the optic disc. Glaucoma was assessed by a consensus group
      of six ophthalmologists that included two glaucoma specialists. Glaucoma was
      diagnosed as possible, probable, or definite. RESULTS: The overall incidence of
      definite OAG was 0.5% (95% confidence limits [CL], 0.3, 0.7); probable and
      definite incidence of OAG was 1.1% (95% CL, 0.8,1.4); and possible, probable, and
      definite OAG incidence was 2.7% (95% CL, 1.8, 3.7). The incidence of possible,
      probable, and definite OAG increases significantly as age increases (P < 0.001).
      The incidence of definite OAG increases from 0% of participants aged 40 to 49
      years to 4.1% of participants aged 80 years and older. The incidence of probable
      and definite OAG increases from 0.2% of participants aged 40 to 49 years to 5.4%
      of participants aged 80 years and older. The incidence of possible, probable, and
      definite OAG increases from 0.5% of participants aged 40 to 49 years to 11% of
      participants aged 80 years and older. A nonsignificant but higher incidence of
      definite OAG among men was observed in this study when compared with women (odds
      ratio, 2.2; 95% CL, 0.9, 5.9). Fifty percent of the definite OAG participants
      were undiagnosed. CONCLUSIONS: The incidence of OAG increases significantly with
      age. The undiagnosed cases suggest the need to develop novel community screening
      strategies for glaucoma.

PMID- 12045043
TI  - Sensitivity and specificity of the Swedish interactive threshold algorithm for
      glaucomatous visual field defects.
AB  - PURPOSE: To determine the sensitivity and specificity of two new visual field
      algorithms in detecting glaucomatous visual field defects: (1) Swedish
      interactive threshold algorithm (SITA) standard and (2) SITA fast. DESIGN:
      Prospective observational case series. PARTICIPANTS: Ninety normal subjects and
      82 glaucoma patients. TESTING: Central 30 degrees fields were performed with the
      Humphrey visual field analyzer 30-2 program (Humphrey Systems, Dublin, CA) using
      full threshold, SITA standard, and SITA fast algorithms on the same day for two
      or more sessions within a 1-month period. MAIN OUTCOME MEASURES: Sensitivity and
      specificity in detecting glaucomatous visual field defects with SITA standard and
      SITA fast using full threshold testing as the reference standard. RESULTS: The
      sensitivity of SITA standard and SITA fast in detecting glaucomatous defects
      overall was 98% and 95%, respectively. In the subset of mild glaucomatous field
      defects (26 patients), sensitivity of SITA standard was 92% versus 85% with SITA
      fast. Sensitivity was 100% for both algorithms in moderate to severe glaucomatous
      defects. Specificity for glaucoma defects using SITA standard and SITA fast was
      96% for both algorithms. SITA standard reduced test-taking time from full
      threshold by 52% in normal subjects and 47% in glaucoma patients (P < 0.001).
      SITA fast reduced test-taking time by 72% in normal subjects and 65% in glaucoma
      patients (P < 0.001). Mean deviation values were 0.4 dB and 0.8 dB better in SITA
      standard and SITA fast fields, respectively, in normal subjects (P < 0.001), and
      0.7 dB and 1.2 dB in SITA standard and SITA fast fields, respectively, in
      glaucoma patients (P < 0.001) compared with full threshold values. CONCLUSIONS:
      The new algorithms for measuring visual fields, SITA standard and SITA fast, have
      excellent sensitivity and specificity for glaucomatous visual field loss with
      considerable savings in time.

PMID- 12045044
TI  - Infrequent confirmation of visual field progression.
AB  - OBJECTIVE: To evaluate the effects of the repeatability criteria on the detection
      of change in visual fields by six progression algorithms used in standard
      automated perimetry. DESIGN: Retrospective, observational case series
      PARTICIPANTS: Fifty-one glaucoma patients, each with multiple visual fields
      performed between May 1990 and December 1998, were included. METHODS: Each
      patient's set of visual fields were analyzed using the glaucoma change
      probability, the Early Manifest Glaucoma Trial (EMGT) algorithm, a modified
      glaucoma change probability score, a modified EMGT score, the Advanced Glaucoma
      Intervention Study algorithm, and the Collaborative Initial Glaucoma Treatment
      Study algorithm. MAIN OUTCOME MEASURES: The effects of repeatability on the
      detection of field change, the level of agreement among algorithms, as well as
      the number of eyes identified as changed with each algorithm, were assessed.
      RESULTS: Mean follow-up was 34 months (range, 12-87 months). The average
      percentage of eyes with change based on three consecutive follow-up fields was
      8.2% (4.0%-12.5%). However, of those showing change on the initial follow-up,
      this change from baseline was observed in subsequent examinations on average in
      23% (18%-33%), depending on the algorithm. When change was based on just one
      field, four of the six algorithms noted a significantly greater number of eyes
      with change. The algorithms, however, did not differ significantly when
      confirmation of field change required two versus three consecutive follow-up
      visual fields. CONCLUSIONS: Although current algorithms may help identify change,
      there are inconsistencies among them. We found that requiring repeatable change
      from baseline significantly reduces the number of changed eyes identified with
      each subsequent follow-up field. Identification and confirmation of change in
      visual fields plays an important role in helping to identify true glaucoma
      progression; however, the specific methods to do so have yet to be determined.

PMID- 12045045
TI  - Risk profile of deep sclerectomy for treatment of refractory congenital
      glaucomas.
AB  - OBJECTIVES: To evaluate the effectiveness and risk profile of deep sclerectomy in
      surgery for refractory congenital glaucoma. DESIGN: Retrospective non-comparative
      interventional case series. PARTICIPANTS AND INTERVENTIONS: Ten eyes of eight
      consecutive patients underwent deep sclerectomy for refractory congenital
      glaucoma. The procedure was converted to a trabeculectomy in four eyes and
      supplemented by a trabeculotomy in two eyes. Six eyes had primary congenital
      glaucoma, and four eyes had secondary congenital glaucoma. The patients' ages at
      the time of surgery in our department ranged from 8 months to 14 years. All eyes
      had a history of previous glaucoma surgery. MAIN OUTCOME MEASURES: The surgical
      outcome was assessed in terms of complication rate, intraocular pressure (IOP)
      change, need for surgical revision, or additional glaucoma medication. RESULTS:
      Preoperatively, the mean IOP was 31.9 mmHg (standard deviation [SD], 5.6 mmHg).
      At first follow-up 1 week after surgery, the mean IOP for all eyes was 12.7 mmHg
      (SD, 6.8 mmHg). The average reduction of IOP was statistically significant (P <
      0.001). In accordance with the success criteria, all eyes were ultimately
      classified as failures. Average time to failure was 2.1 months (SD, 3.6 months).
      Specific complications were seen in terms of non-identification of Schlemm's
      canal (40%), choroidal deroofing (10%), and visible perforation of the
      trabeculodescemetic membrane (20%). Further complications were hyphema (40%),
      ocular hypotony (10%), vitreous hemorrhage (10%), and vitreous loss with
      subsequent retinal detachment (10%). CONCLUSIONS: Although deep sclerectomy may
      reduce the IOP in patients with refractory congenital glaucoma, this study
      indicates a specific risk profile associated with deep sclerectomy in surgery for
      refractory congenital glaucoma.

PMID- 12045046
TI  - Intraobserver and interobserver reproducibility in the evaluation of optic disc
      stereometric parameters by Heidelberg Retina Tomograph.
AB  - PURPOSE: To assess intraobserver and interobserver reproducibility of the
      measurement of stereometric parameters of the optic disc by means of the
      Heidelberg Retina Tomograph I (HRT). STUDY DESIGN: Observational study, with
      interobserver variability. PARTICIPANTS: Fifty-five volunteers (healthy subjects
      and patients with glaucoma). METHODS: HRT examination of the optic disc was
      repeated on 3 consecutive days on 1 eye of each of the 55 subjects. During each
      session, five single images were randomly acquired by two independent observers.
      One mean topography image (MTI), based on three single images, was then built at
      each session. For the intraobserver intraimage evaluation, the two observers
      traced their own contour line on one randomly chosen MTI. This procedure was
      repeated three times. For the intraobserver interimage and interobserver
      intra/interimage evaluations, the two observers traced their own contour line on
      the MTI of the first session, which was then automatically superimposed on the
      MTIs of the other two sessions. MAIN OUTCOME MEASURES: Reproducibility of the 12
      stereometric parameters was calculated for each observer by means of the
      intraclass correlation coefficient (ICC). The expected range of variability
      between two independent evaluations was calculated by the scatter-plots of each
      test-retest difference versus their mean. The standard deviation of the mean test
      retest score differences was used to describe the spread of score differences.
      RESULTS: The ICC ranged between 0.79 and 0.99 for intraobserver intraimage and
      between 0.56 and 1 for intraobserver interimage evaluation. The ICC ranged
      between 0.54 and 0.99 for interobserver intraimage and between 0.65 and 0.97 for
      the interobserver interimage evaluation. ICC was almost perfect to perfect for
      planimetric measures (0.81 < ICC < or = 1), substantial to almost perfect for
      volumetric and cup measures (0.61 < ICC < or = 0.99), and moderate to almost
      perfect for retinal nerve fiber layer related measures (0.41 < ICC < 0.99). The
      expected variability was low (95% confidence interval, < +/-9%). Interimage
      evaluation showed a higher variability than intraimage evaluation in both of
      interobserver (P = 0.012) and intraobserver evaluation (P = 0.028 and P = 0.031
      for the two observers). CONCLUSIONS: Measurement of optic disc stereometric
      parameters by HRT is highly reproducible. However, the use of retinal nerve fiber
      layer-related parameters should be taken cautiously. The image acquisition
      induced variability seems larger than the operator-induced variability.

PMID- 12045047
TI  - Supplemental transscleral diode laser cyclophotocoagulation after aqueous shunt
      placement in refractory glaucoma.
AB  - OBJECTIVE: To assess the outcome of supplemental transscleral diode laser
      cyclophotocoagulation after aqueous tube shunt placement to obtain effective
      intraocular pressure (IOP) control. DESIGN: Retrospective non-comparative case
      series. PARTICIPANTS: Twenty-one eyes in 21 subjects with uncontrolled IOP
      despite the presence of an aqueous tube shunt and maximally tolerated glaucoma
      medications. INTERVENTION: Supplemental transscleral diode laser
      cyclophotocoagulation was performed. MAIN OUTCOME MEASURES: Reduction of
      intraocular pressure and reduction of glaucoma medications. RESULTS: Twelve
      adults and nine children underwent supplemental transscleral diode
      cyclophotocoagulation and were followed postoperatively for a mean of 26.9 +/-
      13.4 (standard deviation [SD]) months (range, 7-58 months). Average IOP was
      significantly reduced from a preoperative level of 35.7 +/- 14.7 (SD) mmHg to a
      postoperative level of 13.6 +/- 7.1 (SD) mmHg (P < 0.001) with the mean number of
      medications significantly reduced to 1.5 +/- 1.3 (SD) (P < 0.001). Seven subjects
      (33%) had additional laser treatment to achieve IOP control. Six subjects who
      were therapy failures included three who developed no light perception in the
      setting of proliferative diabetic retinopathy, one subject with chronic angle
      closure glaucoma who gradually developed no light perception after refusing
      further treatment or medication, and two subjects who developed retinal
      detachments. One child who was a qualified success underwent enucleation and
      debulking of an enlarging neurofibroma that caused significant proptosis and
      disfigurement. CONCLUSIONS: In cases of glaucoma that are uncontrolled despite a
      glaucoma aqueous tube shunt and multiple medications, adjunctive transscleral
      diode cyclophotocoagulation treatment(s) is a viable option to lower IOP.

PMID- 12045048
TI  - First application of extremely high-resolution magnetic resonance imaging to
      study microscopic features of normal and LHON human optic nerve.
AB  - PURPOSE: To apply new methods in magnetic resonance imaging (MRI) in resolving
      the histoarchitecture of the human optic nerve obtained from normal individuals
      and a Leber's hereditary optic neuropathy (LHON) case. DESIGN: Small case series-
      clinicopathologic correlation. METHOD: Three optic nerves were obtained from two
      normal subjects, aged 69 and 70, and a LHON/3460 patient, aged 75. The posterior
      pole of the eye with attached optic nerves was fixed in buffered paraformaldehyde
      and placed into a 10-mm quartz tube. Images were acquired in a Bruker AMX500 12
      Tesla microimaging system. The three-dimensional data were acquired with 512 x
      256 x 256 points, yielding a final isotopic resolution of 30 microm. RESULTS: The
      sclera, choroids, and retina were easily distinguished. The nerve fiber layer was
      seen to enter the optic disc and traverse the lamina cribrosa (LC). The
      resolution of the image of the optic nerve head was such that the LC was
      visualized as multiple stacked plates. The fibers emerged from glial columns in
      the LC as distinct fascicles and could be made out to change appearance as they
      became myelinated and expanded in the more posterior nerve. The ophthalmic artery
      and vein were visualized, as were the optic nerve arachnoid and dural sheaths. In
      the Leber's case, the LC plates seemed collapsed or compressed. The axonal
      bundles were atrophic and the pial-collagen septae markedly thickened. The entire
      nerve had shrunk, creating space under the arachnoid, down and around the central
      ophthalmic artery and vein. CONCLUSIONS: These results demonstrate the
      feasibility of using extremely high-resolution magnetic resonance imaging
      (microMRI) to examine the three-dimensional (30 microm) images of the human optic
      nerve. Several atrophic lesions, normally visible only by histopathologic
      examination, were visualized in the Leber's optic nerve. microMRI may eventually
      permit the in vivo visualization of lesions in or about the optic nerve.

PMID- 12045049
TI  - Five-year incidence of age-related maculopathy lesions: the Blue Mountains Eye
      Study.
AB  - PURPOSE: To describe the 5-year incidence and progression of early and late age
      related maculopathy (ARM) lesions. DESIGN: Population-based cohort study.
      PARTICIPANTS: Three thousand six hundred fifty-four noninstitutionalized
      residents, aged 49 years or older, living in the Blue Mountains area west of
      Sydney, Australia, participated in the study during 1992 to 1994. The cohort was
      reexamined after 5 years (1997-1999). Excluding 543 participants who died since
      the baseline, 2335 (75%) survivors attended 5-year follow-up examinations.
      METHODS: Retinal photographs from both examinations were graded using the
      Wisconsin ARM Grading System. Photographs of participants with any ARM lesions at
      either examination were regraded in detail using a modification of the side-by
      side method developed for the Beaver Dam Eye Study. MAIN OUTCOME MEASURES:
      Incidence and progression of ARM lesions were defined in a similar manner to that
      used in the Beaver Dam Eye Study. RESULTS: Incidence rates for all ARM lesions
      increased significantly with age. For late ARM lesions (geographic atrophy and
      neovascular ARM), the overall 5-year incidence was 1.1%. The combined late ARM
      incidence was 0.0%, 0.6%, 2.4%, and 5.4% for participants aged 60 years and
      younger, 60 to 69 years, 70 to 79 years, and 80 years and older at baseline,
      respectively. After excluding participants with either early or late ARM in
      either eye at baseline, the overall 5-year incidence of early ARM was 8.7%,
      including 3.2%, 7.4%, 18.3%, and 14.8% for the corresponding age groups. The
      incidence of neovascular ARM in women was double that for men (P = 0.1).
      CONCLUSIONS: This study has documented the incidence of ARM lesions in an older
      Australian population. The slightly higher incidence of hyperpigmentation found
      in our population compared with the Beaver Dam Eye Study may be due to sample
      variability, or this could reflect real differences between the two populations.
      Our lower incidence of soft drusen could have resulted from our non-inclusion of
      intermediate soft drusen in the soft distinct and indistinct drusen categories.

PMID- 12045050
TI  - Early vascular changes induced by transpupillary thermotherapy of choroidal
      neovascularization.
AB  - OBJECTIVE: To study early direct effects of transpupillary thermotherapy (TTT) on
      choroidal neovascularization (CNV) and choroid. DESIGN: Retrospective,
      noncomparative interventional case series. PARTICIPANTS: Sixty-four eyes with
      subfoveal CNV. INTERVENTION: TTT was delivered using a diode laser at 810 nm
      through a contact lens. Exposure time was 60 seconds with a power/diameter ratio
      of 247 mW/mm. The end point was an invisible treatment with no color change at
      the retina level. MAIN OUTCOME MEASURES: Fluorescein and indocyanine green
      angiographic findings within 1 hour, and at 1, 2, and 4 weeks after TTT. RESULTS:
      Fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed
      within 1 hour after TTT showed increased leakage of CNV and choroidal vessels.
      Follow-up at 1 and 2 weeks demonstrated a hypofluorescent area corresponding to
      the laser spot and absence of angiographic leakage seen on FA and ICGA. At 4
      weeks after TTT, FA showed mottled hypofluorescence-hyperfluorescence of the TTT
      treated area and absence of angiographic leakage. CONCLUSIONS: TTT induces a
      characteristic dynamic sequence of vascular changes. Treatment with TTT can lead
      to absence of angiographic (FA and ICGA) leakage for 4 weeks. Determination of
      the long-term efficacy and visual implications awaits the results of clinical
      trials.

PMID- 12045051
TI  - Hyperhomocyst(e)inemia, but not methylenetetrahydrofolate reductase C677T
      mutation, as a risk factor in branch retinal vein occlusion.
AB  - OBJECTIVE: To determine whether hyperhomocyst(e)inemia and
      methylenetetrahydrofolate reductase (MTHFR) C677T mutation are associated with
      branch retinal vein occlusion (BRVO). DESIGN: Retrospective, case-control study.
      PARTICIPANTS: The study cohort consisted of 84 consecutive patients with branch
      retinal vein occlusion and 84 controls, matched for age and gender. MAIN OUTCOME
      MEASURES: Fasting plasma homocyst(e)ine, folate, and vitamin B(12) levels, MTHFR
      C677T genotypes. RESULTS: Mean plasma homocyst(e)ine levels were significantly
      higher in patients than in controls (11.4 +/- 4.3 micromol/l vs. 9.9 +/- 2.8
      micromol/l; P = 0.002). An increase of plasma homocyst(e)ine level by 1
      micromol/l was associated with an odds ratio of 1.19 (95% confidence interval
      1.06-1.34; P = 0.004). Mean plasma folate levels were significantly lower in
      patients than in the control group (4.5 +/- 2.1 ng/ml vs. 5.6 +/- 2.1 ng/ml; P =
      0.007). The prevalence of the homozygous genotype of the MTHFR C677T mutation did
      not differ significantly between patients and controls. CONCLUSIONS: Our results
      suggest that hyperhomocyst(e)inemia, but not homozygosity for the MTHFR C677T
      mutation, is associated with BRVO. Increased plasma homocyst(e)ine levels in our
      study are not the result of an increased prevalence of the homozygous genotype of
      MTHFR C677T mutation.

PMID- 12045052
TI  - Atypical presentation of pattern dystrophy in two families with peripherin/RDS
      mutations.
AB  - PURPOSE: To describe the atypical clinical presentations of pattern dystrophy
      (PD) in two unrelated families with novel peripherin/RDS mutations. DESIGN:
      Observational case reports and family genetic study with review of peripherin/RDS
      mutations. PARTICIPANTS: Affected and unaffected members of two families with PD.
      METHODS: The probands of two families, as well as other family members, underwent
      an ophthalmologic assessment including slit-lamp biomicroscopy, applanation
      tonometry, and a dilated fundus examination. Goldmann visual fields and
      fluorescein angiography were performed, wherever appropriate. Blood samples were
      obtained from affected and selected unaffected members of the families for DNA
      analysis. RESULTS: The proband of family 1 had an acute onset of decreased vision
      and a yellowish lesion in both maculae that appeared inflammatory. However,
      resolution of the acute lesion ultimately resulted in fundus changes more typical
      for PD. Moreover, the proband's sister showed more classic-appearing PD lesions.
      Screening of the peripherin/RDS gene for sequence variations showed a 2-bp
      deletion, resulting in a translational frameshift at codon 290 in affected
      members of the family. The proband's father, who showed this sequence variation,
      did not have a macular lesion. The proband of family 2 was asymptomatic and
      showed a fundus phenotype similar to fundus flavimaculatus. The patient had
      normal visual acuity and did not demonstrate a "dark choroid" on fluorescein
      angiography. Molecular screening showed a Gln331stop variation in the
      peripherin/RDS gene. CONCLUSIONS: We describe two novel mutations in the
      peripherin/RDS gene in two unrelated families with PD. Clinicians should
      recognize the atypical features that may occur in patients with PD. A suspected
      diagnosis of PD may be confirmed by the identification of a mutation in the
      peripherin/RDS gene. In isolated family members with PD, a mutation in this gene
      may occur even in the absence of a clinically discernible macular lesion.

PMID- 12045053
TI  - Luxated intraocular lens fixation using intravitreal cow hitch (girth) knot.
AB  - OBJECTIVE: To describe a technique for suturing a luxated intraocular lens (IOL)
      in the vitreous cavity to the ciliary sulcus using intraocular cow hitch (girth)
      knots without IOL extraction. DESIGN: Non-comparative interventional case series.
      PARTICIPANTS: Five patients with a luxated IOL in the vitreous cavity.
      INTERVENTION: All patients underwent surgery to fixate the IOL using this
      technique. METHODS: A three-port vitrectomy was performed in all five cases. A
      needle with looped 10-0 polypropylene was introduced into the vitreous cavity
      through a sclerotomy incision, and only the needle was passed out of the eye,
      guided by a bent 27-gauge needle from the 3-o'clock position 1.5 mm from the
      limbus. A cow hitch (girth) knot at the end of the loop was made outside the
      globe, grasped with a straight intravitreal forceps, and introduced into the
      vitreous cavity. Hooking the cow hitch (girth) knot around the haptics of the IOL
      in the vitreous cavity, the 10-0 polypropylene was pulled so that the IOL haptic
      was fixated onto the sulcus. After the opposite haptic was brought into the
      anterior chamber, the 10-0 polypropylene was looped around the haptics of the IOL
      and manipulated with a push-and-pull hook in the anterior chamber through the two
      corneal side ports to make a cow hitch (girth) knot outside the anterior chamber.
      By pulling up the suture, the knot was brought back and tied in the anterior
      chamber. It was then fixated to the ciliary sulcus at the 9-o'clock position.
      MAIN OUTCOME MEASURES: Patients were evaluated for visual acuity, refraction, and
      surgical complications associated with the procedure. RESULTS: In all five cases,
      the IOL fixated stably and remained well positioned. No significant
      intraoperative or postoperative complications occurred. CONCLUSIONS: This
      technique enables secure fixation of the luxated IOL in the vitreous without
      extracting it.

PMID- 12045054
TI  - Diagnostic yield of vitrectomy in eyes with suspected posterior segment infection
      or malignancy.
AB  - PURPOSE: To determine the yield of diagnostic pars plana vitrectomy in eyes with
      suspected posterior segment inflammation or malignancy when clinical examination
      and systemic laboratory testing did not yield a specific diagnosis. DESIGN: Non
      comparative interventional case series PARTICIPANTS: Eighty-seven consecutive
      patients (90 eyes) who underwent diagnostic pars plana vitrectomy from 1989
      through 1999. INTERVENTIONS: Vitreous samples were analyzed in a directed manner
      based on the preoperative clinical examination and systemic laboratory testing.
      MAIN OUTCOME MEASURES: Diagnosis from each test performed on the vitreous
      samples. RESULTS: Diagnostic vitrectomy was performed alone in 6 eyes (7%) and as
      part of a therapeutic procedure in the remaining 84 eyes. The diagnostic tests
      performed most frequently included cytopathology (83%), microbiologic culture and
      sensitivity (43%), polymerase chain reaction (PCR) (36%), and intraocular
      antibody levels for T. canis (14%). Of these, intraocular antibody testing and
      PCR had the highest positive yield, 46% and 39%, respectively. Overall, directed
      vitreous analysis identified a specific cause in 35 eyes (39%). Of the 65 cases
      in which an underlying infection was suspected preoperatively, the procedure
      yielded a specific diagnosis in 27 (42%). When intraocular malignancy was
      considered preoperatively (71 eyes), a diagnosis of intraocular lymphoma was
      obtained in seven (10%). This difference between these diagnostic yields was
      significant (P = 0.02, Fisher's exact test). CONCLUSIONS: Diagnostic vitrectomy
      with directed vitreous fluid analysis yields a specific cause and guides
      subsequent therapy in a high percentage of cases. This procedure is a valuable
      adjunct in cases that cannot be diagnosed by less invasive methods.

PMID- 12045056
TI  - Changes in ultrasound findings in posterior uveal melanoma after Ruthenium 106
      brachytherapy.
AB  - PURPOSE: To analyze the postbrachytherapy ultrasonographic dynamics of uveal
      melanoma tumor height and internal reflectivity. DESIGN: Prospective,
      comparative, observational case series. PARTICIPANTS: One hundred forty-seven
      patients (147 eyes) with posterior uveal melanoma having a mean age of 61 years
      (range, 29-97 years) who were treated with Ruthenium 106 brachytherapy. METHODS:
      Patients were followed-up with ultrasonography using both A and B modes of
      standardized echography every 6.7 +/- 0.3 months (mean +/- standard error of the
      mean) for a total of 1001 ultrasound examinations. On average, each patient was
      examined 5.8 times (range, 3-17 times). The echographic parameters included tumor
      base size, height, internal reflectivity, regularity, vascularity, and extra
      scleral extension. To compare the response of tumors of different sizes, each
      tumor was standardized to its initial size at brachytherapy. MAIN OUTCOME
      MEASURES: The dynamics of the tumor height and internal reflectivity. RESULTS: At
      the time of brachytherapy, the mean height of the tumors was 5.2 mm (range, 2.2
      11.8 mm). After brachytherapy, 142 tumors (96.6%) responded by a decrease in
      height. The decrease in height was at an initial rate of approximately 3% per
      month. Most of the tumors did not regress entirely; rather, their height
      stabilized on a constant value (on average 61% of the initial height) after
      approximately 18 to 24 months. The decrease in height after brachytherapy was
      best fitted by the sum of a first order exponential decay and a constant (h = 61
      + 35*e(-0.12t), in which t = time in months). The half-life of the decay was 5.8
      months. Large tumors (>8 mm) had a faster initial decrease in height, and
      stabilized on a lower percentage of their initial height (50%) compared with
      small tumors (70%). Thus, the half-life of the height exponential decay was 5.3
      months for small tumors (2-4 mm) and 3.3 months for the large tumors (>8 mm).
      Internal reflectivity increased from a mean of 40% before therapy to 70% after 2
      years. The dynamics of the reflectivity were best fitted with the function: f =
      45 + 24(1-e(-0.09t)). Larger tumors, which initially had lower internal
      reflectivity, presented with a slower increase in internal reflectivity (t() =
      8.7 months) compared with smaller tumors (t(1/2) = 5 months). CONCLUSIONS: The
      postbrachytherapy ultrasonographic dynamics of uveal melanomas resemble a
      function composed of the sum of a constant and a first order exponent, suggesting
      the possible existence of two components (cell populations), one unaffected by
      brachytherapy and the other a radiosensitive population that reacts to
      brachytherapy in an exponential decay. An exponential decay can imply that the
      postbrachytherapy death of each tumor cell is a stochastic Markovian process that
      is independent of the death of other tumor cells.

PMID- 12045055
TI  - Chemothermotherapy in the management of retinoblastoma.
AB  - OBJECTIVE: To evaluate the results of chemothermotherapy for the treatment of
      retinoblastoma. DESIGN: Non-comparative interventional case series. PATIENTS:
      Fifty-one children (65 eyes and 103 tumors) were treated with chemothermotherapy
      in a single institution from January 1995 to May 1998. METHODS:
      Chemothermotherapy consists of a combination of transpupillary thermotherapy
      delivered shortly after intravenous (IV) injection of carboplatin (560 mg/m(2)).
      Each tumor is treated separately with a diode laser using a microscope. Laser
      intensity, spot size, and duration are adapted to the size of each tumor and to
      the clinical response. After 8 days, thermotherapy alone is repeated. This cycle
      is performed from one to six times, every 28 days. The treatment data and outcome
      are analyzed separately. MAIN OUTCOME MEASURES: Assessment of local tumor
      control. RESULTS: One hundred three tumors were treated in 65 eyes of 51
      children. Age at diagnosis was 0 to 60 months (median, 7 months). Median tumor
      diameter at the time of treatment was 3.5 mm (range, 1.5-12 mm). Laser modalities
      were as follows: median intensity, 450 mW (range, 150-1000 mW); median spot size,
      1.2 mm (range, 0.3-2.0 mm); and median number of cycles required to obtain tumor
      control, three. Tumor regression was obtained for 99 tumors (96.1%) after a
      median follow-up of 30 months (17-61 months). Seven tumors relapsed after initial
      control (6.8%). Salvage treatment (external beam radiation, iodine plaques, or
      enucleation) was necessary for a total of 11 tumors (10.7%). The only risk factor
      for relapse was the initial diameter of the lesion greater than 3.5 mm, whereas
      the other tumor characteristics or treatment variables were not significantly
      correlated with relapse. Ninety-seven percent of treated eyes were able to be
      preserved, and 92% of cases were treated without external beam radiation.
      CONCLUSIONS: Chemothermotherapy is an effective technique to treat small- to
      medium-sized retinoblastomas in children, avoiding external beam irradiation.

PMID- 12045057
TI  - Bilateral ophthalmic artery occlusion in a patient with acquired immunodeficiency
      syndrome and central nervous system lymphoma.
AB  - PURPOSE: Clinical course and autopsy findings in a patient with human
      immunodeficiency virus-1 immunodeficiency, central nervous system lymphoma, and
      bilateral, simultaneous ophthalmic artery occlusions. DESIGN: Observational case
      report. METHODS: Clinical examination, fundus photography, gross and microscopic
      pathologic study. RESULTS: Fundus photographs disclosed stasis in retinal
      arterioles, the absence of a cherry-red spot; internal carotid arteriography
      disclosed bilateral ophthalmic artery occlusions; postmortem histopathologic
      examination disclosed bilateral ophthalmic artery atherosclerosis, retinal
      ischemic necrosis, ischemic optic neuropathy, diffuse large-cell lymphoma of
      multiple areas of the central nervous system, cytomegalovirus encephalitis,
      atherosclerosis, and bronchopneumonia. CONCLUSIONS: A 47-year-old male with
      acquired immunodeficiency syndrome, profound immunodeficiency, systemic
      hypertension, and central nervous system lymphoma, developed deep vein
      thrombosis, bilateral ophthalmic artery occlusions, and died of pneumonia 7 weeks
      after the onset of blindness. Postmortem study revealed bilateral ophthalmic
      artery hemorrhagic atherosclerosis, ischemic optic neuropathy, ischemic retinal
      necrosis, diffuse large-cell central nervous system lymphoma, cytomegalovirus
      encephalitis, pneumonitis, and systemic atherosclerosis.

PMID- 12045058
TI  - Effect of hyperopic laser in situ keratomileusis on ocular alignment and
      stereopsis in patients with accommodative esotropia.
AB  - OBJECTIVE: To evaluate the effect of laser in situ keratomileusis (LASIK) on
      ocular alignment and stereopsis in patients with accommodative esotropia. DESIGN:
      Retrospective, non-comparative, interventional case series. PARTICIPANTS: Since
      1998, 27 patients (mean age, 33.3 years; range, 10-52 years) with comitant
      esophoria or esotropia and hyperopia meeting eligibility requirements underwent
      bilateral LASIK for correction of refractive error. INTERVENTION: Bilateral
      hyperopic LASIK was performed using the Technolas Keracor 217 excimer laser
      (Bausch & Lomb) in 22 patients and using the Nidek 5000 excimer laser in 5
      patients. MAIN OUTCOME MEASURES: Visual acuity (best-corrected and uncorrected),
      refractive error, ocular alignment, and stereopsis were recorded before and after
      LASIK. Log transformation of each visual acuity was done before data analysis.
      RESULTS: Using paired t tests, the mean uncorrected esotropia was significantly
      reduced from 9.0 prism diopters (PD) (range, 0 [esophoria only] to 20 PD;
      standard deviation [SD], 7.39) before surgery to 3.3 PD (range, 0-15 PD; SD,
      6.20) after surgery (P < 0.0001). Most patients (14 patients, 58%) had a
      reduction in esodeviation after LASIK, but 10 patients (42%) had no response to
      surgery, and these patients could not be predicted on the basis of preoperative
      sensorimotor testing. No patient had a worsening sensorimotor status after LASIK.
      Nine patients subsequently underwent conventional eye muscle surgery.
      CONCLUSIONS: Hyperopic LASIK was effective in reducing the mean uncorrected
      esotropia in this group of patients. However, accurately determining those
      patients most likely to benefit from the procedure was difficult.

PMID- 12045059
TI  - Higher order wavefront aberrations of cornea and magnitude of refractive
      correction in laser in situ keratomileusis.
AB  - OBJECTIVE: To assess the relation between magnitude of refractive correction and
      changes in higher order wavefront aberrations of the cornea after laser in situ
      keratomileusis. DESIGN: Prospective, consecutive, nonrandomized comparative trial
      (self-controlled). PARTICIPANTS: One hundred eyes of 53 patients with myopia (
      2.0 to -13.0 diopters) were included. INTERVENTION: Laser in situ keratomileusis
      was performed. Videokeratography measurements were conducted before and 1 month
      after surgery. MAIN OUTCOME MEASURES: The videokeratography data were used to
      calculate the higher order wavefront aberrations of the cornea for both small (3
      mm) and large (6 mm) pupils. RESULTS: For a 3-mm pupil, the surgery significantly
      increased coma-like (2.4 +/- 1.3-fold, P < 0.001, paired t test) and spherical
      like (1.8 +/- 0.9-fold, P < 0.001) aberrations. For a 6-mm pupil, both coma-like
      (4.4 +/- 3.3-fold, P < 0.001) and spherical-like (9.4 +/- 5.2-fold, P < 0.001)
      aberrations were significantly increased by surgery. The amount of achieved
      correction showed significant correlations with the changes in coma-like (Pearson
      correlation coefficient r = 0.446, P < 0.001) and spherical-like (r = 0.348, P <
      0.001) aberrations for a 3-mm pupil, and coma-like (r = 0.566, P < 0.001) and
      spherical-like (r = 0.693, P < 0.001) aberrations for a 6-mm pupil. The eyes that
      lost 2 or more lines of baseline spectacle-corrected visual acuity showed
      significantly larger induced increases in coma-like (P = 0.003, Mann-Whitney U
      test) and spherical-like (P = 0.009) aberrations for a 3-mm pupil than those that
      either improved or remained within 1 line of spectacle-corrected visual acuity
      CONCLUSIONS: Laser in situ keratomileusis, performed using the current
      algorithms, increases higher order wavefront aberrations of the cornea, dependent
      on the amount of refractive correction.

PMID- 12045060
TI  - Long-term outcome of keratolimbal allograft with or without penetrating
      keratoplasty for total limbal stem cell deficiency.
AB  - PURPOSE: To evaluate the long-term outcome of ocular surface reconstruction,
      including keratolimbal allograft (KLAL) and amniotic membrane transplantation
      (AMT) with or without penetrating keratoplasty (PKP), in patients with
      nonambulatory vision secondary to total limbal stem cell deficiency (LSCD).
      DESIGN: Retrospective, non-comparative interventional case series. PARTICIPANTS:
      Thirty-nine eyes in 31 consecutive patients with total LSCD, as defined by
      impression cytology, who had a preoperative best-corrected visual acuity of less
      than 20/200 and a minimum follow-up of 12 months. Patients were divided into
      three groups: group 1 (16 eyes) with chemical burns, group 2 (9 eyes) with
      Stevens-Johnson syndrome (SJS), and group 3 (14 eyes) with other causes of LSCD,
      including ocular cicatricial pemphigoid, atopic keratoconjunctivitis, and
      aniridia. INTERVENTION: All patients underwent KLAL and AMT by one surgeon
      (SCGT). If needed, PKP was performed at the same surgical setting using tissue
      from the same donor. MAIN OUTCOME MEASURES: Cumulative rates of survival of
      ambulatory vision (> or = 20/200), survival of KLAL, survival of PKP, and
      incidence of complications. RESULTS: Fifty-three KLAL with AMT procedures were
      performed in 39 eyes, of which 23 eyes received simultaneous PKP at the time of
      the first KLAL. The mean follow-up was 34.0 +/- 21.5 months (range, 12-117.6).
      The mean period of ambulatory vision was 23.9 +/- 20.9 months (range, 0-104). The
      overall survival of ambulatory vision was 53.6% at 3 years and 44.6% at 5 years.
      The survival of ambulatory vision was significantly worse in SJS compared with
      other causes (67%, 81%, and 92% for groups 1, 2, and 3, respectively; P = 0.06
      for group 1 versus 2, P = 0.0008 for group 1 versus 3). KLAL performed alone
      resulted in higher survival of ambulatory vision at 2 years (86.1% +/- 9.1%)
      compared with KLAL with PKP (46.9% +/- 10.6%, P = 0.100). The survival of PKP was
      significantly worse in SJS compared with the other causes (20.0% +/- 17.9%
      compared with 55.6% +/- 11.7%, respectively, P = 0.028). After 2 years, the
      survival of the second KLAL was better than that of the first: 68.2% +/- 15.4%
      compared with 27.3% +/- 13.4%, respectively (P = 0.041). CONCLUSIONS: Ambulatory
      vision for a period of more than 2 years can be achieved by KLAL with or without
      PKP in eyes with severe ocular surface disorders caused by total LSCD. However, a
      progressive decline of the visual outcome and graft survival is evident with
      time. Performing PKP simultaneously with KLAL may be associated with a less
      favorable outcome. The failure of KLAL is associated with the loss of donor cells
      in the recipient. Augmentation of ocular surface defense is essential in securing
      the success of KLAL and PKP. Future modifications of the surgical procedure and
      of the immune suppressive protocols may improve survival of the allogeneic grafts
      and the final visual outcome.

PMID- 12045061
TI  - CD-34 stromal expression pattern in normal and altered human corneas.
AB  - OBJECTIVE: To test CD-34 immunoreactivity in stromal cornea cells in normal and
      pathologic samples obtained from penetrating keratoplasty. DESIGN: Prospective,
      consecutive histopathologic human tissue study. PARTICIPANTS AND CONTROLS: One
      hundred two cornea buttons from patients with different diseases, submitted for
      cornea transplant, were examined. Controls were expired corneas from healthy
      donor patients who died (n = 4), and globes enucleated for primitive intraocular
      neoplasias, that is, retinoblastomas (n = 8), and malignant choroidal melanomas
      (n = 2). METHODS: The expression of CD-34 in stromal cornea cells was examined by
      immunohistochemistry analysis. Other immunohistochemical stains included an
      endothelial cell marker (CD-31), common leukocyte antigen, and alpha-smooth
      muscle actin. MAIN OUTCOME MEASURES: Different diseases that may cause blindness
      and require penetrating keratoplasty have been tested for CD-34 immunoreactivity.
      RESULTS: In control corneas, keratocytes present strong and consistent CD-34
      immunoreactivity. Diseases leading to the loss of transparency and penetrating
      keratoplasty, such as keratoconus, herpes keratitis, trauma, and heredofamilial
      dystrophies, are associated with focal or diffuse loss of CD-34 expression,
      whereas pseudophakic bullous keratopathy and Fuchs' endothelial dystrophy show
      normal CD-34 immunoreactivity in most cases and patchy unstained stromal areas in
      a few cases. CONCLUSIONS: Scar tissue formation in the cornea, as in herpes
      keratitis and trauma, is always associated with loss of CD-34 immunoreactivity,
      which may otherwise be a primary event in keratoconus and heredofamilial
      dystrophies. Both in the pseudophakic bullous keratopathy and Fuchs' endothelial
      dystrophy, CD-34 immunoreactivity may be normal or lost, hence these two diseases
      may be considered as one and part of the same group with regard to CD-34
      expression, as revealed by immunohistochemistry analysis.

PMID- 12045062
TI  - A 1-year prospective clinical trial of balafilcon a (PureVision) silicone
      hydrogel contact lenses used on a 30-day continuous wear schedule.
AB  - PURPOSE: To evaluate silicone-hydrogel balafilcon A (PureVision, Bausch & Lomb
      Inc., Rochester, NY) contact lenses worn on a 30-day continuous wear basis when
      compared with a traditional hydrogel (Acuvue, Vistakon, Johnson and Johnson
      Vision Products, Inc., Jacksonville, FL) worn on a 7-day extended wear schedule.
      DESIGN: Prospective, comparative, paired-eye, interventional, multicenter
      clinical trial. PARTICIPANTS: Two hundred twelve ametropes with no significant
      ocular pathology. METHODS: Subjects with normal ocular health who conformed to a
      set of standard criteria were monitored at seven different sites around the
      globe. Subjects wore both study lenses simultaneously, one on each eye. Lenses
      were assigned to right and left eyes according to a randomized schedule. The
      silicone hydrogel was removed and replaced every month and the traditional
      hydrogel was removed every 7 days and replaced at 14-day intervals. Subjects were
      followed for up to 1 year with discontinuation on indication divided between lens
      related causes, unrelated factors, and loss to follow-up. MAIN OUTCOME MEASURES:
      Discontinuations, symptoms, vision, lens fit, lens surface assessment, slit-lamp
      assessment, and patient preferences. RESULTS: One hundred twenty three subjects
      completed the 12-month wearing period. There were no vision-threatening events
      with either lens type. The silicone-hydrogel lenses showed statistically superior
      performance in physiologic terms with regard to epithelial microcysts, striae,
      corneal staining, limbal injection, and bulbar injection. Inflammatory reactions,
      such as corneal infiltrates and tarsal conjunctival abnormalities occurred at
      similar rates between the lens types. Visible deposition and postlens debris with
      associated transient corneal indentation were significantly lower with the
      traditional hydrogel material at specific time points in the study. Visual acuity
      was comparable with the two lens types. Subjects rated the silicone-hydrogel
      material as preferable on subjective scales of dryness, comfort, and lens
      handling. Overall subjective performance was rated superior with the silicone
      hydrogel material. CONCLUSIONS: The high oxygen performance of the silicone
      hydrogel lenses provides a superior physiologic environment compared with a
      traditional hydrogel material during continuous wear. Despite the slightly higher
      levels of visible deposit on the silicone-hydrogels, superior subjective
      responses suggest that the plasma coating technology on these lenses is effective
      in providing comfortable lens wear. The results look promising for the success of
      silicone-hydrogels as the material of choice for continuous wear contact lenses.

PMID- 12045063
TI  - Acanthamoeba sclerokeratitis: treatment with systemic immunosuppression.
AB  - OBJECTIVE: This study describes the clinical features, management, and outcome of
      19 patients who had severe Acanthamoeba sclerokeratitis (ASK) unresponsive to
      conventional management, requiring systemic immunosuppression to control disease.
      DESIGN: Retrospective, non-comparative, interventional case series. PARTICIPANTS:
      Records of all patients with Acanthamoeba keratitis treated at Moorfields Eye
      Hospital between 1989 and 2000 were reviewed. From more than 200 patients, 19 who
      developed ASK treated with systemic immunosuppression were identified. MAIN
      OUTCOME MEASURES: Visual acuity, level of pain, and degree of inflammation were
      recorded after immunosuppressive treatment. RESULTS: ASK requiring
      immunosuppression occurred in 20 eyes of 19 patients (11 males and 8 females).
      The mean age (mean +/- standard deviation) at onset was 38.6 +/- 13.2 years. On
      presentation, best-corrected visual acuity was counting fingers or worse in 11
      eyes (55%), 6/18 to 6/60 in 5 eyes (25%), and 6/12 or better in 4 eyes (20%). The
      mean time between onset of initial symptoms of Acanthamoeba keratitis and
      commencement of systemic immunosuppression was 4.8 +/- 3.5 months. The mean
      duration of immunosuppression required to control inflammation was 7.2 +/- 3.9
      months. Severe scleritic pain remained uncontrolled in two patients and resulted
      in enucleation. Best-corrected visual acuity at final follow-up was counting
      fingers or worse in eight eyes (40%), 6/18 to 6/60 in six eyes (30%), and 20/40
      or better in six eyes (30%). The mean follow-up period after resolution of
      inflammation was 24.3 +/- 20.9 months (range, 0.2-59.7 months). CONCLUSIONS: ASK
      is an uncommon complication of Acanthamoeba keratitis. The scleritis associated
      with this infection seems to be an immune-mediated response. After topical
      amebicidal treatment, systemic immunosuppression may be required to control the
      pain and tissue destruction associated with ASK.

PMID- 12045064
TI  - Treatment of upper eyelid retraction associated with thyroid eye disease with
      subconjunctival botulinum toxin injection.
AB  - OBJECTIVE: To study the effectiveness of botulinum toxin injections, via a
      subconjunctival approach, in the management of upper eyelid retraction associated
      with thyroid eye disease. DESIGN: Prospective, non-comparative, interventional
      case series. PARTICIPANTS: Eleven patients with upper scleral exposure associated
      with thyroid eye disease who declined conservative or conventional surgical
      management. INTERVENTION: One or more treatments with injections of botulinum
      toxin into the subconjunctival space at the superior margin of the tarsal plate,
      via a conjunctival approach. MAIN OUTCOME MEASURES: Upper eyelid position in
      relation to the upper limbus, patient satisfaction, and complications. RESULTS:
      All patients experienced some improvement in the amount of lid retraction after
      injections. The amount of lid lowering varied between patients and lasted between
      1 and 40 months. A lid position acceptable to the patient was obtained in 10
      patients. Four patients had ptosis lasting from 1 to 3 weeks, and three patients
      had transient diplopia lasting 1 day to 3 weeks. CONCLUSIONS: This
      subconjunctival method of botulinum toxin injection provides an effective
      treatment for upper eyelid retraction associated with thyroid eye disease that is
      easy to administer and well tolerated by patients with few side effects.

PMID- 12045065
TI  - Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in
      patients with metastatic breast cancer.
AB  - PURPOSE: To compare the frequency of canalicular stenosis as a side effect of
      weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer.
      DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS:
      Eighteen patients enrolled in a phase II study of weekly docetaxel plus
      trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks
      docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive
      ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and,
      in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora
      (excessive tearing) was reported by the patient, its time of onset was
      documented. In patients with epiphora, presence or absence of canalicular
      stenosis was evaluated on the basis of the findings on probing and irrigation.
      The duration of treatment with docetaxel, the dose frequency, and the cumulative
      dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%)
      receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients
      had significant anatomic narrowing of the canaliculi. Bicanalicular silicone
      intubation or dacryocystorhinostomy was recommended in all nine patients. Eight
      patients underwent surgery and experienced complete or near complete resolution
      of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus
      doxorubicin reported transient symptoms of epiphora, neither patient was found to
      have narrowing of the canaliculi, and the epiphora was not severe enough to
      justify surgical intervention. The mean duration of docetaxel therapy for the
      patients in this study was 19 weeks. The mean cumulative dose of docetaxel was
      higher in patients with canalicular stenosis than in patients without this side
      effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving
      weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic
      breast cancer. Bicanalicular silicone intubation early in the course of weekly
      docetaxel therapy should be considered, because this intervention can prevent
      complete closure of the canaliculi. Once complete or near complete stenosis of
      the canaliculi occurs, placement of a permanent Pyrex glass tube may become
      necessary to overcome the blockage of tear outflow.

PMID- 12045066
TI  - A novel ophthalmic presentation of the Proteus syndrome.
AB  - PURPOSE: To report a patient with the Proteus syndrome who had ocular
      complications not previously described in the literature. DESIGN: Single
      observational case report. METHODS: Retrospective review of the medical record
      and review of the literature. RESULTS: The 26-year-old man has systemic features
      fulfilling the diagnostic criteria for the Proteus syndrome. His ocular
      abnormalities are myopia, mild calcific band keratopathy, cataract, abnormal
      vitreous structure, vitreous hemorrhage, a large chorioretinal mass, and a
      resolved serous retinal detachment. CONCLUSIONS: Ocular complications are
      frequently reported in patients with the Proteus syndrome. Few of the patients
      reported in the literature have had comprehensive ocular examination by an
      ophthalmologist. Our patient is unique because he has been examined by
      ophthalmologists from childhood, and it is clear that the ocular findings may
      change with time. As far as we are aware, calcific band keratopathy, abnormal
      vitreous structure, and chorioretinal hamartoma associated with serous retinal
      detachment and vitreous hemorrhage have not previously been described.

PMID- 12045067
TI  - Delta opiates increase ischemic tolerance in isolated rabbit jejunum.
AB  - Mammalian hibernation is mediated by humoral agonists of the delta opioid
      receptor (DOR). Moreover, transfer of either humoral or synthetic DOR agonists to
      non-hibernators reportedly induces a state of improved myocardial ischemic
      tolerance. OBJECTIVE: To determine whether the DOR agonist D-Ala 2, D-Leu 5,
      enkephalin (DADLE) similarly elicits protection in noncardiac-i.e., mesenteric
      tissue. METHODS: In Protocols 1 and 2, the authors developed and characterized an
      in vitro model of mesenteric ischemia/reperfusion in isolated rabbit jejunum by
      documenting the effect of increasing ischemic duration (0 to 120 minutes) and the
      relative importance of glucose and/or oxygen deprivation on the evolution of
      jejunal injury. In Protocol 3, jejunal segments were randomized to receive either
      no treatment (controls) or 15 minutes of pretreatment with 1 microM DADLE,
      followed by 60 minutes of simulated ischemia and 30 minutes of reperfusion.
      Jejunal injury was quantified by repeated, time-matched assessment of peak
      contractile force evoked by 1 microM acetylcholine (all protocols) and
      delineation of tissue necrosis (Protocol 1). RESULTS: Development of significant
      jejunal injury required combined oxygen/glucose deprivation. Moreover, there was
      a direct relationship between ischemic duration and tissue injury, and a
      significant inverse correlation between reperfusion contractile force (% of
      baseline) and the extent of smooth muscle necrosis (r(2) = 0.87; p < 0.01). Most
      notably, mesenteric ischemia/reperfusion injury was attenuated by DADLE:
      reperfusion contractile force was 47 +/- 5% versus 36 +/- 5% in DADLE-treated
      versus control segments (p < 0.01). CONCLUSIONS: Treatment with the delta opioid
      agonist DADLE increases ischemic tolerance of isolated rabbit jejunum.

PMID- 12045068
TI  - Validation of the Canadian clinical probability model for acute venous
      thrombosis.
AB  - OBJECTIVE: To validate the predictive value of the Canadian clinical probability
      model for acute venous thrombosis, which, to the best of the authors' knowledge,
      has not been done in emergency department (ED) settings outside of Canada.
      METHODS: Demographic and clinical information, rapid D-dimer testing, and venous
      ultrasound imaging were obtained among patients presenting with clinically
      suspected venous thrombosis at a university-affiliated ED. A diagnosis of deep
      venous thrombosis (DVT) was made based on venous ultrasound test results or
      objectively documented venous thromboembolism during a 12-week follow-up period.
      The probability of venous thrombosis was calculated using the Canadian clinical
      probability model. RESULTS: Among 102 patients, 17 (17%) were diagnosed as having
      venous thrombosis initially or during the three-month follow-up period. The
      frequency of venous thrombosis among patients categorized as having high
      probability was 10 of 17 [59%, 95% confidence interval (95% CI) = 35% to 82%], 6
      of 44 (14%, 95% CI = 4% to 24%) with intermediate probability, and 1 of 41 (2%,
      95% CI = 0.1% to 11%) with low probability. This compares with respective values
      of 49%, 14%, and 3%, reported by Canadian researchers in an ED study. Forty-one
      of 102 (40%) patients had an alternate diagnosis as likely or more likely than
      venous thrombosis, but only three (7%, 95% CI = 2% to 18%) of these had venous
      thrombosis. CONCLUSIONS: Use of the Canadian probability model for DVT in this ED
      resulted in effective risk stratification, comparable to previously published
      results.

PMID- 12045069
TI  - Evaluation of guidelines for ordering prothrombin and partial thromboplastin
      times.
AB  - OBJECTIVES: Existing clinical practice guidelines for ordering prothrombin time
      (PT) and partial thromboplastin time (PTT) tests in the emergency department (ED)
      include physician expectation of an invasive procedure as a criterion. This study
      sought to determine whether this criterion accurately identifies patients who
      undergo an invasive procedure and whether an amalgam of these guidelines
      identifies patients at low risk of an adverse medical outcome. METHODS: A
      prospective observational cohort study of adults treated in a university medical
      center ED between July 1997 and March 1998. Physicians were surveyed at order
      placement to determine the presence of guideline criteria. Adverse clinical
      outcomes defined as an International Normalized Ratio [INR] > 1.3 or PTT > 39.9
      seconds combined with consequent directed medical therapy were abstracted from ED
      and the first 24 hours of inpatient medical records. RESULTS: The sensitivity of
      ED physician expectation of an invasive procedure was 60.0%; therefore, it was
      excluded from both the PT and PTT guidelines. There were 553 patients with a PT
      test order; test order indications were absent in 190 (34.4%), of which one
      (0.5%, 95% CI = 0.1% to 2.9%) had adverse outcomes. There were 547 patients with
      a PTT test; test order indications were absent in 226 (41.3%), of which three
      (1.3%, 95% CI = 0.4 to 3.8%) had adverse outcomes. All three were taking warfarin
      when they presented to the ED. CONCLUSIONS: Emergency department physician
      expectation of an invasive procedure for patients with PT or PTT test orders is
      an insensitive predictor of patients who undergo such procedures. Clinical
      practice guidelines that exclude this criterion identify ED patients at the time
      of ED presentation at low risk for adverse medical outcomes in the ED or shortly
      after admission.

PMID- 12045070
TI  - Emergency department resuscitative procedures: animal laboratory training
      improves procedural competency and speed.
AB  - Certain resuscitative procedures can be lifesaving, but are performed
      infrequently by emergency medicine (EM) residents on human subjects. Alternative
      training methods for gaining procedural proficiency must be explored and tested.
      OBJECTIVE: To test whether animal laboratory training (ALT) is associated with
      sustained improvement in procedural competency and speed. METHODS: After watching
      an educational videotape of saphenous cutdown (SAPH), thoracotomy (THOR), and
      cricothyroidotomy (CRIC), EM residents were randomized to receive either a
      tutored ALT session on live anesthetized pigs (Group A) or no ALT session (Group
      B). Residents were tested six months later by performing procedures on live
      anesthetized pigs. Videotaped procedures were evaluated by blinded examiners for
      the number of critical steps, complications, and procedure times. RESULTS: Group
      A (n = 10) achieved a higher number of critical steps compared with Group B (n =
      8) for SAPH (15.4 +/- 0.7 vs. 9.0 +/- 1.8, p = 0.03) and THOR (17.4 +/- 0.6 vs.
      12.3 +/- 1.6, p = 0.009), but not CRIC (18.1 +/- 0.4 vs. 16.2 +/- 1.0, p = 0.1).
      Group A completed procedures in less time than Group B for SAPH (Wilcoxon chi(2)
      = 4.0, p = 0.04) and THOR (chi(2) = 4.4, p = 0.04), but not CRIC (chi(2) = 0.9, p
      = 0.3). There was no difference in the number of complications for any of the
      procedures. CONCLUSION: Residents with animal laboratory training six months
      prior to testing demonstrated improved procedural competency and speed in the
      performance of resuscitative procedures.

PMID- 12045072
TI  - The performance of procedures on the recently deceased.
AB  - OBJECTIVE: To determine the prevalence of performing procedures on the recently
      deceased for training purposes in emergency departments (EDs) with emergency
      medicine (EM) training programs. METHODS: Surveys were mailed to program
      directors of Accreditation Council for Graduate Medical Education (ACGME)
      approved residency programs in EM. A check-off system was used to identify which
      procedures were performed and who performed the procedure. The survey also
      documented whether consent was obtained and whether written policies exist that
      address this issue. A Likert scale was used to evaluate respondents' attitudes
      toward this practice. RESULTS: Ninety-six (83%) of 116 surveys were returned.
      Forty-seven percent of the respondents indicated procedures were performed on the
      recently deceased for teaching purposes in their EDs. Emergency medicine
      residents perform the procedures in all departments where this practice occurs,
      with off-service residents and medical students using this technique in half of
      those departments. Paramedics, flight nurses, and attending physicians
      occasionally use this resource. Endotracheal intubation was the most commonly
      performed procedure. Seventy-six percent stated they "almost never" obtain
      consent from family members. Only four of 96 respondents have written policies
      concerning this practice. The majority of program directors (69%) would favor a
      position statement from a national EM organization concerning this issue, while
      11% were opposed. CONCLUSIONS: The performance of procedures on the recently
      deceased is a common and important practice in EM training programs. Consent is
      infrequently obtained and policies concerning this practice are rare and
      restrictive when present.

PMID- 12045071
TI  - Radiology services in emergency medicine residency programs: a national survey.
AB  - OBJECTIVES: To determine who reads plain film radiographs, how quickly
      radiologists' interpretations are available, how many initial readings require
      correction, and how satisfied emergency physicians (EPs) are with radiology in
      emergency departments (EDs) with emergency medicine (EM) residency programs.
      METHODS: A questionnaire was sent to the chairs of all U.S. EM residencies,
      asking about EM radiology services. RESULTS: Of 120 sites surveyed, 97 (81%)
      responded. Respondents reported that, on weekday days, EM attendings or residents
      performed the radiograph interpretation used for clinical decision making at 66%
      of sites; on nights and weekends, EPs performed the clinically relevant readings
      at 79% of sites. Twenty-one percent of sites reported that no radiologist
      reviewed images before patients left the ED on nights and weekends. Only 39% of
      sites reported that all images were read within four hours on weekday days, and
      only 19% of sites reported readings within this time frame on nights and
      weekends. Median misinterpretation rates were reported as 1% on weekday days and
      1.5% at other times. Overall, EPs were satisfied with their interactions with
      radiology at 63% of EDs. CONCLUSIONS: This study summarizes the perceptions of
      EPs regarding radiology services; the findings must be interpreted with caution,
      given the lack of external validation. Nevertheless, EPs report that many EM
      residency programs depend on EPs' interpretations of radiographs. Emergency
      physicians report that attending radiologists rarely read images on nights and
      weekends and that images are misread more frequently at these times. Although EPs
      were satisfied with many aspects of radiology, EPs expressed the most
      dissatisfaction with turnaround times and misreads.

PMID- 12045073
TI  - Behavioral risk factor and preventive health care practice survey of immigrants
      in the emergency department.
AB  - OBJECTIVE: To compare the demographic profiles, behavioral risk factors, and
      preventive health care practices of adult immigrant and non-immigrant patients
      while considering the effects of various socioeconomic variables. METHODS: This
      was a prospective survey administered at a large urban emergency department in
      New York City. Study subjects were adult immigrant patients presenting in an
      eight-week period in 1998. One non-immigrant control patient was recruited
      concurrently with every two immigrant patients. Differences between immigrants
      and non-immigrants were evaluated using the chi-square test. Multivariate
      logistic regression models were used to adjust for confounding variables.
      RESULTS: Eight hundred sixty-nine immigrant patients from 80 countries and 354
      non-immigrant patients completed surveys. Immigrants were more likely not to have
      reached high school (28.9% vs 8.5%; p < 0.001), to have annual family incomes
      less than $20,000 (73.8% vs 64.5%; p < 0.01), and to have no health coverage
      (51.7% vs 30.8%; p < 0.001). Immigrant women were more likely never to have had a
      Papanicolaou test (16.1% vs 1.4%; OR 11.24, 95% CI = 2.70 to 46.8) and never to
      have performed a self-breast examination (20.8% vs 7.5%; OR 2.03, 95% CI = 1.29
      to 3.20). Immigrants were more likely not to use condoms (63.4% vs 42.8%; OR
      1.61, 95% CI = 1.20 to 2.15) and never to have visited a dentist (21.2% vs 7.8;
      OR 2.54, 95% CI = 1.60 to 4.04). Immigrants were more likely never to have
      received a purified protein derivative (PPD) skin test (30.3% vs 9.1%; OR 3.85,
      95% CI = 2.56 to 5.80) and never to have received a tetanus immunization (48.1%
      vs 13.5%; OR 3.09, 95% CI = 2.17 to 4.42). These differences were independent of
      age, gender, marital status, employment, education, income, and health insurance
      status. When analyzing the immigrant group alone, region of origin, length of
      time in the United States, and English ability were significant independent
      predictors of higher-risk behavioral profiles and poor preventive health care
      practices. CONCLUSIONS: Differences exist between the socioeconomic profiles,
      behavioral risk profiles, and preventive health care practices of immigrant and
      non-immigrant patients presenting to a large inner-city municipal emergency
      department. Different populations within a heterogeneous group of immigrants have
      distinct health risks and public health needs.

PMID- 12045074
TI  - Parents and practitioners are poor judges of young children's pain severity.
AB  - OBJECTIVE: Visual analog pain scales are reliable measures in older children and
      adults; however, pain studies that include young children often rely on parental
      or practitioner assessments for measuring pain severity. The authors correlated
      patient, parental, and practitioner pain assessments for young children with
      acute pain. METHODS: This was a prospective, descriptive study of a convenience
      sample of 63 emergency department patients aged 4-7 years, with acute pain
      resulting from acute illness or painful invasive procedures. A trained research
      assistant administered a structured pain survey containing demographic and
      historical features to all parents/guardians. Children assessed their pain
      severity using a validated ordinal scale that uses five different faces with
      varying degrees of frowning (severe pain) or smiling (no pain). Each face was
      converted to a numeric value from 0 (no pain) to 4 (severe pain). Parents and
      practitioners independently assessed their child's pain using a validated 100-mm
      visual analog scale (VAS) marked "most pain" at the high end. Pairwise
      correlations between child, parent, and practitioner pain assessments were
      performed using Spearman's or Pearson's test as appropriate. The association
      between categorical data was assessed using chi(2) tests. RESULTS: Sixty-three
      children ranging in age from 4 to 7 were included. Mean age (+/-SD) was 5.7 (+/
      1.1); 42% were female. Fifty-seven successfully completed the face scale. The
      distribution of the children's scores was 0-17%, 1-9%, 2-30%, 3-14%, and 4-30%.
      Mean parental and practitioner scores (+/-SD) on the VAS were 61 (+/-26) mm and
      37 (+/-26) mm, respectively (maximal = 100 mm). Correlation between child and
      parent scores was 0.47 (p < 0.001). Correlation between child and practitioner
      scores was 0.08 (p = 0.54). Correlation between parent and practitioner scores
      was 0.04 (p = 0.001). CONCLUSIONS: There is poor agreement between pain ratings
      by children, parents, and practitioners. It is unclear which assessment best
      approximates the true degree of pain the child is experiencing.

PMID- 12045075
TI  - Resuscitation of cells and systems: the PULSE research initiative. Post
      Resuscitative and Initial Utility of Life Saving Efforts.

PMID- 12045077
TI  - Droperidol--behind the black box warning.

PMID- 12045078
TI  - Simple but not perfect.

PMID- 12045079
TI  - Scientific priorities and strategic planning for resuscitation research and life
      saving therapy following traumatic injury: report of the PULSE Trauma Work Group.
AB  - Traumatic injury and its sequelae remain a major, unrecognized public health
      problem in North America. Traumatic injury is the principal cause of death in
      patients aged 1-44 years and the overall leading cause of life-years lost in the
      United States. Recognizing this, the National Heart, Lung, and Blood Institute
      (NHLBI), in conjunction with other federal agencies, organized a conference in
      June 2000 to discuss the basic and clinical research needs that could lead to
      improved outcomes following cardiopulmonary or post injury resuscitation. The
      Post Resuscitative and Initial Utility of Life Saving Efforts (PULSE) Workshop
      resulted and eight work groups were established to focus on various aspects,
      including organ systems, pharmacology, epidemiology, and trauma. The Trauma Work
      Group recommendations are presented in this article. Despite the recognition of
      improved survival and outcome through advancements in trauma systems and trauma
      care, the National Institutes of Health (NIH) support ratio for trauma research
      is only 0.10, compared with 1.65 for cancer research and a remarkable 3.51 for
      AIDS and HIV infection research. The successful federal HIV research program has
      significantly decreased the morbidity and mortality over the last ten years at a
      cost of $1.4 billion per year. A coordinated trauma research program should aim
      to replicate the success achieved by such programs; however, a centralized
      federal "home" for trauma research does not exist. Consequently, the existing
      limited research support is derived from NIH institutes in addition to other
      federal and state agencies. This report serves to describe some of the obstacles
      and outline various strategies and priorities for basic science, clinical, and
      translational trauma resuscitation research.

PMID- 12045080
TI  - Preventive care in the emergency department: screening and brief intervention for
      alcohol problems in the emergency department: a systematic review.
AB  - OBJECTIVE: To systematically review the medical literature in order to determine
      the strength of the recommendation for screening and brief intervention (SBI) for
      alcohol-related problems in the emergency department (ED) setting. METHODS: The
      review followed the methodology of systematic reviews and was facilitated through
      the use of a structured template, a companion explanatory piece, and a grading
      and methodological scoring system based on published criteria for critical
      appraisal. The primary outcome measure was the prevention of mortality and
      morbidity secondary to alcohol-related illnesses/injuries. The secondary outcome
      measures included: decreased consumption; fewer ED/outpatient visits and
      hospitalizations; a decrease in social consequences; and increased referrals for
      follow-up and/or treatment. Three Medline searches as well as a search of the
      Cochrane Library were performed. Two team members reviewed the abstracts and
      selected pertinent articles. References were screened for additional pertinent
      articles. RESULTS: Twenty-seven articles were identified and reviewed, in
      addition to the 14 primary articles included in the 1996 U.S. Preventive Services
      Task Force Report. The study populations were diverse, including inpatient,
      outpatient, and college settings, with ages ranging from 12 to 70 years. Four
      studies were ED-based and two included EDs as one of multiple sites. Thirty-nine
      studies on SBI, 30 randomized controlled and nine cohort, were used to formulate
      the current recommendation. A positive effect of the intervention was
      demonstrated in 32 of these studies. CONCLUSIONS: The authors recommend that SBI
      for alcohol-related problems in the ED be incorporated into clinical practice.

PMID- 12045081
TI  - Referral of medically uninsured emergency department patients to primary care.
AB  - OBJECTIVE: To examine the impact primary care referral has on subsequent
      emergency department (ED) utilization. METHODS: Uninsured ED patients who
      reported not having a primary care (PC) provider were referred to PC services at
      a community health center (CHC). The number of CHC visits completed was
      documented and the utilization rates of hospital-based services (i.e., ED visits,
      outpatient clinic visits, and admissions) were compared for patients who
      completed a CHC visit and those who did not before and after referral. RESULTS:
      Of the 655 referred patients, 22% completed at least one CHC visit. Patients who
      completed a visit were more likely to be older, to be female, and to have a
      chronic medical problem (p = 0.001). The number of visits to the CHC was
      significantly related to the payment method. Only 19% of those who were self-pay
      completed three or more CHC visits, compared with 63% of those who qualified for
      a sliding fee or insurance (p < 0.001). There was no significant difference in
      pre- or post-ED utilization between those who completed a CHC visit and those who
      did not. The only significant difference in utilization between the two study
      groups was for subsequent outpatient visits. Patients who completed a CHC visit
      were more likely to receive outpatient specialty care (23%) compared with
      patients who did not (12%) (p = 0.001). CONCLUSIONS: For uninsured patients with
      no regular health care provider, improving access to primary care services is not
      enough to reduce their visits to the ED.

PMID- 12045083
TI  - Selective use of ultrasonography for the detection of pneumoperitoneum.
AB  - OBJECTIVE: Whether ultrasonography is superior to plain radiography for the
      detection of pneumoperitoneum is unknown. The goal of this study was to determine
      the value of ultrasonography for the detection of pneumoperitoneum. METHODS: One
      hundred thirty-two patients with suspected hollow-organ perforation were
      prospectively selected for study. All 132 patients received ultrasonography,
      upright chest radiography, and left lateral decubitus abdominal radiography
      examinations. The diagnostic accuracies of chest and abdominal radiographs for
      the detection of pneumoperitoneum were compared with corresponding values from
      ultrasonography. RESULTS: Of the 125 patients who underwent laparotomy, 121
      patients had hollow-organ perforation, three patients had perforated
      appendicitis, and one patient had acute cholecystitis. For the diagnosis of
      pneumoperitoneum, ultrasonography demonstrated a sensitivity of 93%, a
      specificity of 64%, a positive predictive value of 97%, a negative predictive
      value of 44%, and an accuracy of 90%. Plain radiography revealed a sensitivity of
      79%, a specificity of 64%, a positive predictive value of 96%, a negative
      predictive value of 21%, and an accuracy of 77%. CONCLUSIONS: Ultrasonography is
      a more sensitive diagnosing modality than plain radiography for the diagnosis of
      pneumoperitoneum. The authors suggest that ultrasonography was a useful
      diagnostic modality when plain radiographs failed to reveal pneumoperitoneum
      among patients with suspected hollow-organ perforation.

PMID- 12045084
TI  - Low prevalence of Chlamydia trachomatis by urinary ligase chain reaction in women
      patients in the emergency department.
AB  - Recent studies suggest that women with acute urethral syndrome or abdominal pain,
      presenting to emergency departments (EDs), have a high prevalence of Chlamydia
      trachomatis. OBJECTIVES: To estimate the prevalence of C. trachomatis in women
      presenting to an ED and to see whether those with dysuria or abdominal pain have
      a higher prevalence of C. trachomatis. METHODS: The authors conducted a
      prospective cross-sectional study of C. trachomatis in the urine of women aged 18
      to 50 years who had a urinalysis performed at a university/county ED from
      February through May 1998. Urine specimens were labeled for the presence of
      symptoms and analyzed for C. trachomatis by ligase chain reaction (LCR).
      Polymerase chain reaction (PCR) testing of cervical swabs for C. trachomatis was
      done for usual clinical indications. Difference in proportions of positive LCR
      tests among patients was tested with Fisher's exact test. Agreement between PCR
      and LCR was measured using Cohen's kappa statistic. RESULTS: Of 397 women whose
      urine was tested, 280 had symptoms of dysuria, abdominal pain, or both, and 117
      had no symptoms. The overall prevalence of C. trachomatis by LCR was 3.8% (95% CI
      = 2.1% to 6.2%); and the combined PCR-LCR prevalence was 4.3% (95% CI = 2.5% to
      6.8%). The presence of symptoms was not associated with a positive LCR test for
      C. trachomatis (p = 0.26, power = 0.8, alpha = 0.05, difference 3% vs. 12%). In
      the 172 patients who had both a PCR cervical swab and urine LCR, agreement was
      excellent (kappa = 0.67, 95% CI = 0.45 to 0.90). CONCLUSIONS: This ED had a
      surprisingly low prevalence of C. trachomatis. Women with symptoms were not more
      likely to test positive than those without.

PMID- 12045086
TI  - A simple plan--faculty compensation in an academic department of emergency
      medicine.
AB  - An equitable and effective compensation system is essential to the smooth and
      productive operation of any academic department. While academic departments of
      emergency medicine must meet clinical, teaching, research, and administrative
      missions, they are disproportionately reliant on funds derived from clinical
      activities. The Department of Emergency Medicine at UCSD is a freestanding
      academic hospital department with responsibility and accountability for its own
      finances. The compensation system addresses the reliance on clinical income yet
      recognizes the other, largely underfunded, missions. All salaries are comprised
      of a base amount tied to the core clinical workload, scaleable stipends for
      academic rank, years of service, and administrative role, as well as a provision
      for clinical bonus and additional clinical workload. Faculty have the option of
      adjusting clinical workload with resultant formulaic modification of departmental
      salary support. Salary adjustment fosters the core value of clinical service and
      provides incentive for senior faculty to remain clinically active. The system has
      been in place for more than six years and has been associated with an excellent
      record of patient care, teaching, academic productivity, administrative service,
      faculty stability, and fiscal integrity.

PMID- 12045085
TI  - Intramuscular droperidol versus intramuscular dimenhydrinate for the treatment of
      acute peripheral vertigo in the emergency department: a randomized clinical
      trial.
AB  - OBJECTIVE: The emergency department (ED) treatment of acute peripheral vertigo
      (APV) has not been well studied. The purpose of this study was to determine the
      efficacy of intramuscular (IM) droperidol vs IM dimenhydrinate, in the treatment
      of ED patients with APV. METHODS: The study was a randomized, double-blinded
      clinical trial, performed at a suburban, teaching ED. A convenience sample of
      adult patients with symptoms and signs consistent with rigid diagnostic criteria
      for APV were randomized to one of two treatment groups. Patients more than 65
      years of age were excluded to reduce the likelihood of diagnostic
      misclassification. Demographic and historical features were recorded on a
      standardized data form. Patients recorded their initial level (t0) of discomfort
      on a 10-centimeter (cm) visual analog scale (VAS). Treatment group 1 received 2.5
      mg droperidol IM, while treatment group 2 received 50 mg dimenhydrinate IM. After
      30 minutes (t30), patients again recorded the severity of their symptoms on the
      VAS. Chi-square, t-tests, and Mann-Whitney were used for statistical comparison
      as appropriate. All tests were two-tailed, with alpha set at 0.05. Primary
      outcome parameters were the mean change in VAS score from t0 to t30, and the
      percentage of patients in each treatment group who felt well enough to go home
      after t30 without further ED intervention. RESULTS: There were 20 patients in the
      droperidol group and 20 in the dimenhydrinate group. The two groups were similar
      with respect to mean age (40 +/- 13 years droperidol vs. 42 +/- 13 years
      dimenhydrinate; p = 0.6), female sex (60% vs. 50%; p = 0.7), and mean median
      duration of symptoms [3 (interquartile range 2-12) vs 9 (interquartile range 2
      30) hours; p = 0.2]. Mean initial t0 VAS scores were 7.2 +/- 2.3 and 7.8 +/- 1.9
      (p = 0.47). Both treatment groups had mean reductions in VAS scores at t30 of 3.3
      [95% confidence interval (95% CI) = 2.3 to 4.3]. At t30, 42% of patients in the
      droperidol group and 45% of patients in the dimenhydrinate group felt well enough
      to go home without further ED intervention. CONCLUSIONS: The authors found no
      difference between the therapeutic efficacies of IM droperidol and dimenhydrinate
      for the treatment of acute peripheral vertigo.

PMID- 12045087
TI  - Patient descriptors in injection drug abuse.

PMID- 12045088
TI  - Discoveries of vitamin B12 and selenium enzymes.
AB  - My undergraduate education at Cornell University was followed by graduate studies
      on methane fermentations under the guidance of H.A. Barker at the University of
      California, Berkeley. My Ph.D. degree was granted in June 1949. Two anaerobic
      microorganisms isolated from the mud flats of San Francisco Bay served as sources
      of biochemical research material for later studies at the National Institutes of
      Health in Bethesda. These organisms, Methanococcus vannielii and Clostridium
      sticklandii, proved to be especially rich sources of selenium-dependent enzymes
      and seleno-tRNAs. New B12 coenzyme-dependent enzymes that catalyzed intermediate
      steps in the anaerobic conversion of lysine to fatty acids and ammonia were
      isolated from C. sticklandii and characterized. My research efforts since 1970
      have dealt primarily with various aspects of selenium biochemistry. We have shown
      that selenium is an essential constituent of several enzymes in prokaryotes. Se
      is present in these either as a selenocysteine residue in the protein or
      alternatively, in a few molybdoenzymes, as a component of a bound cofactor.
      Recent studies with a human adenocarcinoma cell line led to the unexpected
      discovery that selenocysteine occurs in mammalian thioredoxin reductase. The
      selenium located in a redox center of this enzyme is essential for catalytic
      activity.

PMID- 12045089
TI  - Error-prone repair DNA polymerases in prokaryotes and eukaryotes.
AB  - DNA repair is crucial to the well-being of all organisms from unicellular life
      forms to humans. A rich tapestry of mechanistic studies on DNA repair has emerged
      thanks to the recent discovery of Y-family DNA polymerases. Many Y-family members
      carry out aberrant DNA synthesis-poor replication accuracy, the favored formation
      of non-Watson-Crick base pairs, efficient mismatch extension, and most
      importantly, an ability to replicate through DNA damage. This review is devoted
      primarily to a discussion of Y-family polymerase members that exhibit error-prone
      behavior. Roles for these remarkable enzymes occur in widely disparate DNA repair
      pathways, such as UV-induced mutagenesis, adaptive mutation, avoidance of skin
      cancer, and induction of somatic cell hypermutation of immunoglobulin genes.
      Individual polymerases engaged in multiple repair pathways pose challenging
      questions about their roles in targeting and trafficking. Macromolecular
      assemblies of replication-repair "factories" could enable a cell to handle the
      complex logistics governing the rapid migration and exchange of polymerases.

PMID- 12045090
TI  - Long-distance electron transfer through DNA.
AB  - DNA molecules are able to transport electrons over long distances. In most
      experiments the process is stimulated by the oxidation of guanines (G), which
      generates guanine radical cations. The electron transport through DNA occurs in a
      multistep hopping mechanism with all Gs as carriers of the positive charge. The
      rate of each individual hopping step between the Gs decreases strongly with
      increase of the distance. If the (A:T) bridges between the guanines are long,
      adenines (A) also become charge carriers. Mismatches, single strands, and G
      oxidation products can drastically diminish the efficiency of the charge
      transport. But in triplexes and DNA/RNA duplexes, as well as in several duplex
      DNA/peptide complexes, the efficacy of the charge transport is less affected. The
      ability of DNA molecules to transport charges over long distances could provide a
      mechanism for ameliorating the harmfulness of damage to DNA under the conditions
      of oxidative stress.

PMID- 12045091
TI  - The bacterial RecA protein and the recombinational DNA repair of stalled
      replication forks.
AB  - The primary function of bacterial recombination systems is the nonmutagenic
      repair of stalled or collapsed replication forks. The RecA protein plays a
      central role in these repair pathways, and its biochemistry must be considered in
      this context. RecA protein promotes DNA strand exchange, a reaction that
      contributes to fork regression and DNA end invasion steps. RecA protein
      activities, especially formation and disassembly of its filaments, affect many
      additional steps. So far, Escherichia coli RecA appears to be unique among its
      nearly ubiquitous family of homologous proteins in that it possesses a motorlike
      activity that can couple the branch movement in DNA strand exchange to ATP
      hydrolysis. RecA is also a multifunctional protein, serving in different
      biochemical roles for recombinational processes, SOS induction, and mutagenic
      lesion bypass. New biochemical and structural information highlights both the
      similarities and distinctions between RecA and its homologs. Increasingly, those
      differences can be rationalized in terms of biological function.

PMID- 12045092
TI  - V(D)J recombination: RAG proteins, repair factors, and regulation.
AB  - V(D)J recombination is the specialized DNA rearrangement used by cells of the
      immune system to assemble immunoglobulin and T-cell receptor genes from the
      preexisting gene segments. Because there is a large choice of segments to join,
      this process accounts for much of the diversity of the immune response.
      Recombination is initiated by the lymphoid-specific RAG1 and RAG2 proteins, which
      cooperate to make double-strand breaks at specific recognition sequences
      (recombination signal sequences, RSSs). The neighboring coding DNA is converted
      to a hairpin during breakage. Broken ends are then processed and joined with the
      help of several factors also involved in repair of radiation-damaged DNA,
      including the DNA-dependent protein kinase (DNA-PK) and the Ku, Artemis, DNA
      ligase IV, and Xrcc4 proteins, and possibly histone H2AX and the Mre11/Rad50/Nbs1
      complex. There may be other factors not yet known. V(D)J recombination is
      strongly regulated by limiting access to RSS sites within chromatin, so that
      particular sites are available only in certain cell types and developmental
      stages. The roles of enhancers, histone acetylation, and chromatin remodeling
      factors in controlling accessibility are discussed. The RAG proteins are also
      capable of transposing RSS-ended fragments into new DNA sites. This transposition
      helps to explain the mechanism of RAG action and supports earlier proposals that
      V(D)J recombination evolved from an ancient mobile DNA element.

PMID- 12045093
TI  - Eukaryotic DNA polymerases.
AB  - Any living cell is faced with the fundamental task of keeping the genome intact
      in order to develop in an organized manner, to function in a complex environment,
      to divide at the right time, and to die when it is appropriate. To achieve this
      goal, an efficient machinery is required to maintain the genetic information
      encoded in DNA during cell division, DNA repair, DNA recombination, and the
      bypassing of damage in DNA. DNA polymerases (pols) alpha, beta, gamma, delta, and
      epsilon are the key enzymes required to maintain the integrity of the genome
      under all these circumstances. In the last few years the number of known pols,
      including terminal transferase and telomerase, has increased to at least 19. A
      particular pol might have more than one functional task in a cell and a
      particular DNA synthetic event may require more than one pol, which suggests that
      nature has provided various safety mechanisms. This multi-functional feature is
      especially valid for the variety of novel pols identified in the last three
      years. These are the lesion-replicating enzymes pol zeta, pol eta, pol iota, pol
      kappa, and Rev1, and a group of pols called pol theta;, pol lambda, pol micro,
      pol sigma, and pol phi that fulfill a variety of other tasks.

PMID- 12045095
TI  - Active site tightness and substrate fit in DNA replication.
AB  - Various physicochemical factors influence DNA replication fidelity. Since it is
      now known that Watson-Crick hydrogen bonds are not necessary for efficient and
      selective replication of a base pair by DNA polymerase enzymes, a number of
      alternative physical factors have been examined to explain the efficiency of
      these enzymes. Among these factors are minor groove hydrogen bonding, base
      stacking, solvation, and steric effects. We discuss the concept of active site
      tightness in DNA polymerases, and consider how it might influence steric (size
      and shape) effects of nucleotide selection in synthesis of a base pair. A high
      level of active site tightness is expected to lead to higher fidelity relative to
      proteins with looser active sites. We review the current data on what parts and
      dimensions of active sites are most affected by size and shape, based on data
      with modified nucleotides that have been examined as polymerase substrates. We
      also discuss recent data on nucleotide analogs displaying higher fidelity than
      the natural ones. The published data are discussed with a view toward testing
      this sterically based hypothesis and unifying existing observations into a
      narrowly defined range of effects.

PMID- 12045097
TI  - ATP-dependent nucleosome remodeling.
AB  - It has been a long-standing challenge to decipher the principles that enable
      cells to both organize their genomes into compact chromatin and ensure that the
      genetic information remains accessible to regulatory factors and enzymes within
      the confines of the nucleus. The discovery of nucleosome remodeling activities
      that utilize the energy of ATP to render nucleosomal DNA accessible has been a
      great leap forward. In vitro, these enzymes weaken the tight wrapping of DNA
      around the histone octamers, thereby facilitating the sliding of histone octamers
      to neighboring DNA segments, their displacement to unlinked DNA, and the
      accumulation of patches of accessible DNA on the surface of nucleosomes. It is
      presumed that the collective action of these enzymes endows chromatin with
      dynamic properties that govern all nuclear functions dealing with chromatin as a
      substrate. The diverse set of ATPases that qualify as the molecular motors of the
      nucleosome remodeling process have a common history and are part of a
      superfamily. The physiological context of their remodeling action builds on the
      association with a wide range of other proteins to form distinct complexes for
      nucleosome remodeling. This review summarizes the recent progress in our
      understanding of the mechanisms underlying the nucleosome remodeling reaction,
      the targeting of remodeling machines to selected sites in chromatin, and their
      integration into complex regulatory schemes.

PMID- 12045096
TI  - Great metalloclusters in enzymology.
AB  - Metallocluster-containing enzymes catalyze some of the most basic redox
      transformations in the biosphere. The reactions catalyzed by these enzymes
      typically involve small molecules such as N2, CO, and H2 that are used to
      generate both chemical building blocks and energy for metabolic purposes. During
      the past decade, structures have been established for the iron-sulfur-based
      metalloclusters present in the molybdenum nitrogenase, the iron-only hydrogenase,
      and the nickel-carbon monoxide dehydrogenase, and for the copper-sulfide-based
      cluster in nitrous oxide reductase. Although these clusters are built from
      interactions observed in simpler metalloproteins, they contain novel features
      that may be relevant for their catalytic function. The mechanisms of
      metallocluster-containing enzymes are still poorly defined, and represent
      substantial and continuing challenges to biochemists, biophysicists, and
      synthetic chemists. These proteins also provide a window into the union of the
      biological and inorganic worlds that may have been relevant to the early
      evolution of biochemical catalysis.

PMID- 12045098
TI  - Biological roles of proteases in parasitic protozoa.
AB  - Proteases from a variety of protozoan parasites have been characterized at the
      molecular and cellular levels, and the many roles that proteases play in these
      organisms are coming into focus. Central roles have been proposed for proteases
      in diverse processes such as host cell invasion and egress, encystation,
      excystation, catabolism of host proteins, differentiation, cell cycle
      progression, cytoadherence, and both stimulation and evasion of host immune
      responses. Detailed structural and functional characterization of parasite
      proteases has led to novel insights into the workings of these fascinating
      catalytic machines. The possibility of developing selective inhibitors of key
      proteases of pathogenic parasites into novel chemotherapeutic strategies is being
      vigorously explored.

PMID- 12045094
TI  - Eukaryotic ribonuclease P: a plurality of ribonucleoprotein enzymes.
AB  - Ribonuclease P (RNase P) is an essential endonuclease that acts early in the tRNA
      biogenesis pathway. This enzyme catalyzes cleavage of the leader sequence of
      precursor tRNAs (pre-tRNAs), generating the mature 5' end of tRNAs. RNase P
      activities have been identified in Bacteria, Archaea, and Eucarya, as well as
      organelles. Most forms of RNase P are ribonucleoproteins, i.e., they consist of
      an essential RNA subunit and protein subunits, although the composition of the
      enzyme in mitochondria and chloroplasts is still under debate. The recent
      purification of the eukaryotic nuclear RNase P has demonstrated a significantly
      larger protein content compared to the bacterial enzyme. Moreover, emerging
      evidence suggests that the eukaryotic RNase P has evolved into at least two
      related nuclear enzymes with distinct functions, RNase P and RNase MRP. Here we
      review current information on RNase P, with emphasis on the composition,
      structure, and functions of the eukaryotic nuclear holoenzyme, and its
      relationship with RNase MRP.

PMID- 12045099
TI  - Metabolism and the control of circadian rhythms.
AB  - The core apparatus that regulates circadian rhythm has been extensively studied
      over the past five years. A looming question remains, however, regarding how this
      apparatus is adjusted to maintain coordination between physiology and the
      changing environment. The diversity of stimuli and input pathways that gain
      access to the circadian clock are summarized. Cellular metabolic states could
      serve to link physiologic perception of the environment to the circadian
      oscillatory apparatus. A simple model, integrating biochemical, cellular, and
      physiologic data, is presented to account for the connection of cellular
      metabolism and circadian rhythm.

PMID- 12045100
TI  - DNA replication in eukaryotic cells.
AB  - The maintenance of the eukaryotic genome requires precisely coordinated
      replication of the entire genome each time a cell divides. To achieve this
      coordination, eukaryotic cells use an ordered series of steps to form several key
      protein assemblies at origins of replication. Recent studies have identified many
      of the protein components of these complexes and the time during the cell cycle
      they assemble at the origin. Interestingly, despite distinct differences in
      origin structure, the identity and order of assembly of eukaryotic replication
      factors is highly conserved across all species. This review describes our current
      understanding of these events and how they are coordinated with cell cycle
      progression. We focus on bringing together the results from different organisms
      to provide a coherent model of the events of initiation. We emphasize recent
      progress in determining the function of the different replication factors once
      they have been assembled at the origin.

PMID- 12045101
TI  - The La protein.
AB  - Ubiquitous in eukaryotic cells, the La protein associates with the 3' termini of
      many newly synthesized small RNAs. RNAs bound by the La protein include all
      nascent transcripts made by RNA polymerase III as well as certain small RNAs
      synthesized by other RNA polymerases. Recent genetic and biochemical analyses
      have revealed that binding by the La protein protects the 3' ends of these RNAs
      from exonucleases. This La-mediated stabilization is required for the normal
      pathway of pre-tRNA maturation, facilitates assembly of small RNAs into
      functional RNA-protein complexes, and contributes to nuclear retention of certain
      small RNAs. Studies of mutant La proteins have given some insights into how the
      La protein specifically recognizes its RNA targets. However, many questions
      remain regarding the molecular mechanisms by which La protein binding influences
      multiple steps in small RNA biogenesis. This review focuses on the roles of the
      La protein in small RNA biogenesis and also discusses data that implicate the La
      protein in the translation of specific mRNAs.

PMID- 12045102
TI  - Lipoprotein receptors in the nervous system.
AB  - The low-density-lipoprotein (LDL) receptor family is an evolutionarily ancient
      gene family of structurally closely related cell-surface receptors. Members of
      the family are involved in the cellular uptake of extracellular ligands and
      regulate diverse biological processes including lipid and vitamin metabolism and
      cell-surface protease activity. Some members of the family also participate in
      cellular signaling and regulate the development and functional maintenance of the
      nervous system. Here we review the roles of this family of multifunctional
      receptors in the nervous system and focus on recent advances toward the
      understanding of the mechanisms by which lipoprotein receptors and their ligands
      transmit and modulate signals in the brain.

PMID- 12045103
TI  - Order out of chaos: assembly of ligand binding sites in heparan sulfate.
AB  - Virtually every cell type in metazoan organisms produces heparan sulfate. These
      complex polysaccharides provide docking sites for numerous protein ligands and
      receptors involved in diverse biological processes, including growth control,
      signal transduction, cell adhesion, hemostasis, and lipid metabolism. The binding
      sites consist of relatively small tracts of variably sulfated glucosamine and
      uronic acid residues in specific arrangements. Their formation occurs in a tissue
      specific fashion, generated by the action of a large family of enzymes involved
      in nucleotide sugar metabolism, polymer formation (glycosyltransferases), and
      chain processing (sulfotransferases and an epimerase). New insights into the
      specificity and organization of the biosynthetic apparatus have emerged from
      genetic studies of cultured cells, nematodes, fruit flies, zebrafish, rodents,
      and humans. This review covers recent developments in the field and provides a
      resource for investigators interested in the incredible diversity and specificity
      of this process.

PMID- 12045104
TI  - Neuronal CA2+/calmodulin-dependent protein kinase II: the role of structure and
      autoregulation in cellular function.
AB  - Highly enriched in brain tissue and present throughout the body,
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is central to the
      coordination and execution of Ca(2+) signal transduction. The substrates
      phosphorylated by CaMKII are implicated in homeostatic regulation of the cell, as
      well as in activity-dependent changes in neuronal function that appear to
      underlie complex cognitive and behavioral responses, including learning and
      memory. The architecture of CaMKII holoenzymes is unique in nature. The kinase
      functional domains (12 per holoenzyme) are attached by stalklike appendages to a
      gear-shaped core, grouped into two clusters of six. Each subunit contains a
      catalytic, an autoregulatory, and an association domain. Ca(2+)/calmodulin (CaM)
      binding disinhibits the autoregulatory domain, allowing autophosphorylation and
      complex changes in the enzyme's sensitivity to Ca(2+)/CaM, including the
      generation of Ca(2+)/CaM-independent activity, CaM trapping, and CaM capping.
      These processes confer a type of molecular memory to the autoregulation and
      activity of CaMKII. Its function is intimately shaped by its multimeric
      structure, autoregulation, isozymic type, and subcellular localization; these
      features and processes are discussed as they relate to known and potential
      cellular functions of this multifunctional protein kinase.

PMID- 12045105
TI  - Biochemistry of Na,K-ATPase.
AB  - The Na,K-ATPase or sodium pump carries out the coupled extrusion and uptake of Na
      and K ions across the plasma membranes of cells of most higher eukaryotes. It is
      a member of the P-type ATPase superfamily. This heterodimeric integral membrane
      protein is composed of a 100-kDa alpha-subunit with ten transmembrane segments
      and a heavily glycosylated beta subunit of about 55 kDa, which is a type II
      membrane protein. Current ideas on how the protein achieves active transport are
      based on a fusion of results of transport physiology, protein chemistry, and
      heterologous expression of mutant proteins. Recently acquired high resolution
      structural information provides an important new avenue for a more complete
      understanding of this protein. In this review, the current status of knowledge of
      Na,K-ATPase is discussed, and areas where there is still considerable uncertainty
      are highlighted.

PMID- 12045106
TI  - Mammalian ABC transporters in health and disease.
AB  - The ATP-binding cassette (ABC) transporters are a family of large proteins in
      membranes and are able to transport a variety of compounds through membranes
      against steep concentration gradients at the cost of ATP hydrolysis. The
      available outline of the human genome contains 48 ABC genes; 16 of these have a
      known function and 14 are associated with a defined human disease. Major
      physiological functions of ABC transporters include the transport of lipids, bile
      salts, toxic compounds, and peptides for antigen presentation or other purposes.
      We review the functions of mammalian ABC transporters, emphasizing biochemical
      mechanisms and genetic defects. Our overview illustrates the importance of ABC
      transporters in human physiology, toxicology, pharmacology, and disease. We focus
      on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug
      conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a
      large number of substances, sometimes against a steep concentration gradient.
      Several inborn errors in liver metabolism are due to mutations in one of the
      genes for these pumps; these are discussed. (c) A rapidly increasing number of
      ABC transporters are found to play a role in lipid transport. Defects in each of
      these transporters are involved in human inborn or acquired diseases.

PMID- 12045107
TI  - Homogeneous glycopeptides and glycoproteins for biological investigation.
AB  - Protein glycosylation is widely recognized as a modulator of protein structure,
      localization, and cell-cell recognition in multicellular systems. Glycoproteins
      are typically expressed as mixtures of glycoforms, their oligosaccharides being
      generated by a template-independent biosynthetic process. Investigation of their
      function has been greatly assisted by sources of homogeneous material. This
      review summarizes current efforts to obtain homogeneous glycopeptide and
      glycoprotein materials by a variety of methods that draw from the techniques of
      recombinant expression, chemical synthesis, enzymatic transformation, and
      chemoselective ligation. Some of these techniques remove obstacles to
      glycoprotein synthesis by installing nonnative linkages and other modifications
      for facilitated assembly. The end purpose of the described approaches is the
      production of glycosylated materials for experiments relevant to the biological
      investigation of glycoproteins, although the strategies presented apply to other
      posttranslational modifications as well.

PMID- 12045110
TI  - Nuclear actin and actin-related proteins in chromatin remodeling.
AB  - The existence and function of actin in the nucleus has been hotly debated for
      forty years. Recently, beta-actin was found to be a component of mammalian
      SWI/SNF-like BAF chromatin remodeling complexes and still more recently other
      SWI/SNF-related chromatin remodeling complexes in yeast, flies, and man. Although
      the function of actin in these chromatin remodeling complexes is only starting to
      be explored, the fact that actin is one of the most regulated proteins in the
      cell suggests that control of nuclear actin may be a critical regulatory point in
      the control of chromatin remodeling. Actin rapidly shuttles between the nucleus
      and the cytoplasm offering additional sites and modes of regulation. In addition,
      actin-related proteins (Arps) are also components of these chromatin remodeling
      complexes and have been implicated in transcriptional control in yeast. The
      observation that the BAF chromatin remodeling complex in which actin was
      originally identified, is also a human tumor suppressor complex necessary for the
      actions of the retinoblastoma protein indicates that the study of nuclear actin
      is likely to contribute to understanding cell growth control.

PMID- 12045109
TI  - Formation of unusual sugars: mechanistic studies and biosynthetic applications.
AB  - Carbohydrates are highly abundant biomolecules found extensively in nature.
      Besides playing important roles in energy storage and supply, they often serve as
      essential biosynthetic precursors or structural elements needed to sustain all
      forms of life. A number of unusual sugars that have certain hydroxyl groups
      replaced by a hydrogen, an amino group, or an alkyl side chain play crucial roles
      in determining the biological activity of the parent natural products in
      bacterial lipopolysaccharides or secondary metabolite antibiotics. Recent
      investigation of the biosynthesis of these monosaccharides has led to the
      identification of the gene clusters whose protein products facilitate the unusual
      sugar formation from the ubiquitous NDP-glucose precursors. This review
      summarizes the mechanistic studies of a few enzymes crucial to the biosynthesis
      of C-2, C-3, C-4, and C-6 deoxysugars, the characterization and mutagenesis of
      nucleotidyl transferases that can recognize and couple structural analogs of
      their natural substrates and the identification of glycosyltransferases with
      promiscuous substrate specificity. Information gleaned from these studies has
      allowed pathway engineering, resulting in the creation of new macrolides with
      unnatural deoxysugar moieties for biological activity screening. This represents
      a significant progress toward our goal of searching for more potent agents
      against infectious diseases and malignant tumors.

PMID- 12045111
TI  - Mechanism of fast protein folding.
AB  - An explosion of in vitro experimental data on the folding of proteins has
      revealed many examples of folding in the millisecond or faster timescale, often
      occurring in the absence of stable intermediate states. We review experimental
      methods for measuring fast protein folding kinetics, and then discuss various
      analytical models used to interpret these data. Finally, we classify general
      mechanisms that have been proposed to explain fast protein folding into two
      catagories, heterogeneous and homogeneous, reflecting the nature of the
      transition state. One heterogeneous mechanism, the diffusion-collision mechanism,
      can be used to interpret experimental data for a number of proteins.

PMID- 12045113
TI  - Catalytic proficiency: the unusual case of OMP decarboxylase.
AB  - Enzymes are called upon to differ greatly in the difficulty of the tasks that
      they perform. The catalytic proficiency of an enzyme can be evaluated by
      comparing the second-order rate constant (kcat/Km) with the rate of the
      spontaneous reaction in neutral solution in the absence of a catalyst. The
      proficiencies of enzymes, measured in this way, are matched by their affinity
      constants for the altered substrate in the transition state. These values vary
      from approximately approximately 10(9) M(-1) for carbonic anhydrase to
      approximately 10(23) M(-1) for yeast orotidine 5'-phosphate decarboxylase
      (ODCase). ODCase turns its substrate over with a half-time of 18 ms, in a
      reaction that proceeds in its absence with a half-time of 78 million years in
      neutral solution. ODCase differs from other decarboxylases in that its catalytic
      activity does not depend on the presence of metals or other cofactors, or on the
      formation of a covalent bond to the substrate. Several mechanisms of transition
      state stabilization are considered in terms of ODCase crystal structures observed
      in the presence and absence of bound analogs of the substrate, transition state,
      and product. Very large connectivity effects are indicated by the results of
      experiments testing how transition state stabilization is affected by the
      truncation of binding determinants of the substrate and the active site.

PMID- 12045114
TI  - Catalytic strategies of the hepatitis delta virus ribozymes.
AB  - The hepatitis delta virus (HDV) ribozymes are self-cleaving RNA sequences
      critical to the replication of a small RNA genome. A recently determined crystal
      structure together with biochemical and biophysical studies provides new insight
      into the possible catalytic mechanism of these ribozymes. The HDV ribozymes are
      examples of naturally occurring small ribozymes that catalyze cleavage of the RNA
      backbone with a rate enhancement of 10(6)- to 10(7)-fold over the uncatalyzed
      rate. To achieve this level of rate enhancement, the HDV ribozymes have been
      proposed to employ several catalytic strategies that include the use of metal
      ions, intrinsic binding energy, and a novel example of general acid-base
      catalysis with a cytosine side chain acting as a proton donor or acceptor.

PMID- 12045115
TI  - Acute interstitial pneumonia: clues from the white stuff.

PMID- 12045116
TI  - Pediatric interstitial lung disease: children are not small adults.

PMID- 12045112
TI  - RNA editing by adenosine deaminases that act on RNA.
AB  - ADARs are RNA editing enzymes that target double-stranded regions of nuclear
      encoded RNA and viral RNA. These enzymes are particularly abundant in the nervous
      system, where they diversify the information encoded in the genome, for example,
      by altering codons in mRNAs. The functions of ADARs in known substrates suggest
      that the enzymes serve to fine-tune and optimize many biological pathways, in
      ways that we are only starting to imagine. ADARs are also interesting in regard
      to the remarkable double-stranded structures of their substrates and how enzyme
      specificity is achieved with little regard to sequence. This review summarizes
      ongoing investigations of the enzyme family and their substrates, focusing on
      biological function as well as biochemical mechanism.

PMID- 12045117
TI  - Childhood experiences take away your breath as a young adult.

PMID- 12045108
TI  - Lipopolysaccharide endotoxins.
AB  - Bacterial lipopolysaccharides (LPS) typically consist of a hydrophobic domain
      known as lipid A (or endotoxin), a nonrepeating "core" oligosaccharide, and a
      distal polysaccharide (or O-antigen). Recent genomic data have facilitated study
      of LPS assembly in diverse Gram-negative bacteria, many of which are human or
      plant pathogens, and have established the importance of lateral gene transfer in
      generating structural diversity of O-antigens. Many enzymes of lipid A
      biosynthesis like LpxC have been validated as targets for development of new
      antibiotics. Key genes for lipid A biosynthesis have unexpectedly also been found
      in higher plants, indicating that eukaryotic lipid A-like molecules may exist.
      Most significant has been the identification of the plasma membrane protein TLR4
      as the lipid A signaling receptor of animal cells. TLR4 belongs to a family of
      innate immunity receptors that possess a large extracellular domain of leucine
      rich repeats, a single trans-membrane segment, and a smaller cytoplasmic
      signaling region that engages the adaptor protein MyD88. The expanding knowledge
      of TLR4 specificity and its downstream signaling pathways should provide new
      opportunities for blocking inflammation associated with infection.

PMID- 12045118
TI  - The persistently troublesome cough.

PMID- 12045119
TI  - Enhancing the safety of critically ill patients by reducing urinary and central
      venous catheter-related infections.

PMID- 12045120
TI  - Risk factors for airway remodeling in asthma manifested by a low
      postbronchodilator FEV1/vital capacity ratio: a longitudinal population study
      from childhood to adulthood.
AB  - Airway remodeling may lead to irreversible loss of lung function in asthma. The
      impact of childhood asthma, airway responsiveness, atopy, and smoking on airway
      remodeling was investigated in a birth cohort studied longitudinally to age 26. A
      low postbronchodilator ratio of forced exhaled volume in 1 second (FEV1) to vital
      capacity (VC) at age 18 or 26 was used as a marker of airway remodeling. "Normal"
      study members with no history of asthma ever, no wheezing in the last year, and
      no smoking ever were used to determine sex- and age-specific reference values for
      this ratio. The lower limit of normal was defined as the mean ratio minus 1.96
      standard deviation, delimiting the 2.5% of the normal population with the lowest
      FEV1/VC ratio. A low postbronchodilator FEV1/VC ratio was found in 7.4% and 6.4%
      of study members at ages 18 and age 26 and 4.6% at both assessments. Lung
      function was low throughout childhood in those with a consistently low
      postbronchodilator FEV1/VC ratio at both ages. Those with consistently low
      postbronchodilator ratios also showed a greater decline in the prebronchodilator
      FEV1/VC ratio from ages 9 to 26 compared with those with normal
      postbronchodilator ratios at both ages (males, -12% versus -6%, p < 0.0001;
      females, -10.5% versus -5.5%, p < 0.01). Asthma, male sex, airway
      hyperresponsiveness, and low lung function in childhood were each independently
      associated with a low postbronchodilator FEV1/VC ratio, which in turn was
      associated with an accelerated decline in lung function and decreased
      reversibility. These data suggest that airway remodeling in asthma, as manifested
      by impaired lung function, begins in childhood and continues into adult life.

PMID- 12045121
TI  - Ascaris lumbricoides infection is associated with increased risk of childhood
      asthma and atopy in rural China.
AB  - There is growing international interest in the possible relationships between
      helminthic infection and allergic disease, although the nature of the
      relationships remains uncertain and controversial. The interrelationships of
      current and past infection with Ascaris lumbricoides and asthma and atopy were
      investigated in a cross-sectional sample of 2,164 children between the ages of 8
      and 18 years from Anqing Province, China. The children were sampled from a larger
      family-based study of the genetics of asthma. The prevalence of either a history
      of or a positive stool examination for Ascaris was 24.5%. Asthma was defined for
      analytic purposes using previously validated, stringent criteria including
      airways responsiveness to methacholine. Independently of the other factors
      assessed, infection with A. lumbricoides was associated with increased risk of
      asthma (p < 0.001), an increased number of skin tests positive to aeroallergens
      (p < 0.001), and an increased dose-response slope to methacholine (p = 0.003).
      The association of sensitization to common aeroallergens with increased asthma
      risk was enhanced in those children infected with Ascaris, and such infection was
      associated with an increased risk of asthma independent of sensitization to
      aeroallergens in this selected population. These data suggest a complex
      relationship between ascariasis and susceptibility to childhood asthma among
      predisposed children that may involve an interaction with the immune response to
      inhaled aeroallergens.

PMID- 12045122
TI  - The effect of augmentation therapy on bronchial inflammation in alpha1
      antitrypsin deficiency.
AB  - alpha1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema
      associated with neutrophilic airway inflammation. The efficacy of augmentation
      therapy has not been proven clinically or by demonstrating an effect on airway
      inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg)
      at weekly intervals and monitored both the serum and secretion concentrations of
      AAT as well as markers of neutrophilic inflammation, including myeloperoxidase,
      elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B(4).
      Serum AAT rose and was maintained above the protective threshold. In addition,
      AAT concentrations in the sputum rose from a mean of 0.17 microM (SEM +/- 0.04)
      before therapy to concentrations similar to nondeficient subjects (0.43 +/- 0.12)
      1 week after the first infusion (p < 0.01). This was associated with a reduction
      in elastase activity (p < 0.002) and the chemoattractant leukotriene B(4) (p <
      0.02), which fell from a median baseline value of 13.46 nM (range, 4.17-55.00) to
      8.62 nM (4.23-21.59) the day following the last infusion. Although median values
      for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve
      statistical significance. In summary, short-term therapy with AAT increased lung
      secretion concentrations and was associated with a fall in leukotriene B(4),
      which is thought to be central to the airway inflammation of AAT deficiency.

PMID- 12045123
TI  - Utility of noninvasive pharyngometry in epidemiologic studies of childhood sleep
      disordered breathing.
AB  - Measurement of pharyngeal dimensions may contribute to the characterization of
      anatomic risk factors for sleep-disordered breathing (SDB) in children. Acoustic
      pharyngometry, a noninvasive method, has been used successfully in adults, but
      application in children has been limited. We sought to evaluate the feasibility
      and utility of this technique in children, including assessment of the variation
      of pharyngeal measurements with height, sex, ethnicity, prematurity, and indices
      of SDB. Subjects were drawn from a large, community-based cohort of children of
      age 8-11 years. Demographic, morphologic, and sleep-related information were
      collected via standard questionnaires, direct measurement, and home
      cardiorespiratory monitoring during sleep. Pharyngeal dimensions were assessed in
      203 children using acoustic pharyngometry performed with an optimized mouthpiece.
      In this sample, the coefficient of variation of minimum pharyngeal cross
      sectional area (CSA) and mean CSA were similar to those in adults (8.0 and 11.1%,
      respectively). The minimum CSA, but not mean CSA, was significantly reduced in
      preterm children, habitual snorers, and children with SDB relative to unaffected
      children. Thus, minimum CSA is a useful measure for evaluating SDB risk factors
      in preadolescent children.

PMID- 12045124
TI  - Effects of increasing carboxyhemoglobin on the single breath carbon monoxide
      diffusing capacity.
AB  - Although carboxyhemoglobin (COHb) is often increased in smokers, American
      Thoracic Society recommendations for adjusting the single breath carbon monoxide
      (CO) diffusing capacity (DL(CO)(SB)) for COHb remain optional. Using a previously
      described 3-equation technique, we measured DL(CO)(SB) and an index of diffusion
      inhomogeneity (DI) in 10 healthy, nonsmoking subjects who performed DL(CO)(SB)
      maneuvers both before and after increasing COHb. CO backpressure (FA(CO)) was
      measured from the exhaled gas of a standardized deep breath of room air that
      immediately preceded each DL(CO)(SB) and was validated by measurement of FA(CO)
      from an identical "sham" maneuver without inhaling CO. Without adjustments for
      FA(CO) or COHb, DL(CO)(SB) decreased with increasing COHb. This effect persisted
      when DL(CO)(SB) was adjusted only for FA(CO), but it was eliminated with further
      adjustment for the anemia effect of increasing COHb. The anemia adjustment was
      proportional to the fractional COHb. DI, adjusted for FA(CO), was unaffected by
      increasing COHb. We conclude that DL(CO)(SB) must be adjusted for both the
      buildup of CO backpressure and the anemia effect of increasing COHb. Adequate
      corrections of DL(CO)(SB) can be implemented using FA(CO) measured during a
      standardized deep breath immediately preceding the DL(CO)(SB) maneuver. Current
      American Thoracic Society recommendations for DL(CO)(SB) standardization do not
      adequately compensate for COHb.

PMID- 12045125
TI  - Effect of adenosine triphosphate-sensitive potassium channel openers on lung
      preservation.
AB  - ATP-sensitive potassium channel (KATP) openers have been proven to be involved in
      ischemic preconditioning, which protects ischemic tissue. However, the effect of
      KATP openers on ischemia-reperfusion injury of the lungs remains unknown. We
      investigated whether a KATP opener, pinacidil, can attenuate ischemia-reperfusion
      injury using an ex vivo rat lung model. Heart-lung blocks were flushed and
      preserved with phosphate-buffered saline (control group) or with one of the
      solutions containing pinacidil (pinacidil group) or pinacidil + glibenclamide (a
      KATP blocker) (glibenclamide group). The control and glibenclamide groups showed
      significantly higher values with respect to shunt fraction, pulmonary arterial
      pressure, and peak inspiratory pressure than the pinacidil group. The
      concentrations of total adenine nucleotides and ATP in the lung after reperfusion
      became significantly lower in the control and glibenclamide groups than in the
      fresh group. Lipid peroxidation of the lungs increased significantly in the
      control and glibenclamide groups after reperfusion. State 3 mitochondrial
      respiration and State 3/4 ratios of mitochondrial respiration were significantly
      decreased in the lungs of the control and glibenclamide groups. These findings
      suggested that KATP openers would maintain the mitochondrial respiratory function
      during lung preservation, prevent lipid peroxidation after reperfusion, and
      attenuate ischemia-reperfusion injury.

PMID- 12045126
TI  - Endotoxin induces respiratory failure and increases surfactant turnover and
      respiration independent of alveolocapillary injury in rats.
AB  - Although endotoxin-induced acute lung injury is associated with inflammation,
      alveolocapillary injury, surfactant dysfunction, and altered lung mechanics, the
      precise sequence of these changes is polemic. We have studied the early
      pathogenesis of acute lung injury in spontaneously breathing anesthetized rats
      after intravenous infusion of Salmonella abortus equi endotoxin. The animals
      became hypoxic, and airway resistance, tissue resistance, lung elastance, and
      static compliance all deteriorated well before any change in alveolar
      neutrophils, macrophages, lung fluid (99mTc-labeled diethylenetriamine
      pentaacetic acid), or 125I-albumin flux, which were only appreciably increased at
      8.5 hours. Lung elastance deteriorated before airway resistance, indicating that
      the compliance change was specific rather than caused by reduced lung volume. The
      subcellular and alveolar content of surfactant proteins A and B, cholesterol,
      disaturated phospholipids, and phospholipid classes remained normal in the face
      of a dramatic increase in the synthesis and turnover of 3H-disaturated
      phosphatidylcholine. Our findings indicate that the increase in surfactant
      disaturated phospholipid turnover reflects, at least in part, an approximately
      five-fold increase in "sigh frequency." We suggest that endotoxin has direct
      effects on tissue resistance and lung elastance independent of surfactant
      composition and that the initial respiratory failure results primarily from
      endotoxin-induced ventilation/perfusion mismatch independent of edema or
      alveolocapillary injury per se.

PMID- 12045127
TI  - A prospective, randomized, double-blind study of the tolerability of rifapentine
      600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis
      treatment.
AB  - Once-weekly rifapentine 600 mg plus isoniazid (INH) during the continuation phase
      treatment of tuberculosis is associated with a relapse rate higher than that of
      twice-weekly rifampin plus INH. The safety and tolerability of higher rifapentine
      doses need to be determined. We conducted a prospective, randomized, double-blind
      trial of rifapentine at three doses (600, 900, and 1,200 mg) plus INH 15 mg/kg
      once weekly in the continuation phase treatment of culture-positive tuberculosis
      in 150 human immunodeficiency virus-seronegative adults. Outcome measures were
      discontinuation of therapy for any reason and adverse events on therapy.
      Treatment was discontinued in 3 of 52 (6%), 2 of 51 (4%), and 3 of 47 (6%) in the
      rifapentine 600-, 900-, and 1,200-mg treatment arms, respectively. Only one
      discontinuation, in the rifapentine 1,200-mg arm, was due to an adverse event
      possibly associated with study therapy. There was a trend toward more adverse
      events, possibly associated with study therapy, in the highest-dose arms (p =
      0.051). Rifapentine 900-mg, once-weekly dosing appears to be safe and well
      tolerated and is being evaluated in Phase III efficacy trials of treatment of
      latent tuberculosis. Further evaluation of the safety and tolerability of
      rifapentine 1,200 mg is warranted.

PMID- 12045129
TI  - Identification of cytokeratin 18 as a bronchial epithelial autoantigen associated
      with nonallergic asthma.
AB  - The allergic response to common environmental agents (allergens) has been
      regarded as an important mechanism in the development of airway inflammation of
      patients with asthma. However, allergic sensitization cannot be detected in a
      significant number of adult patients with asthma. The etiologic mechanism
      responsible for nonallergic asthma has not yet been identified. The idea of a
      possible involvement of autoimmunity in the pathogenesis of nonallergic asthma
      has been proposed by earlier studies. To test for the possible presence of an
      autoimmune response to bronchial epithelial cell antigens in nonallergic asthma,
      we examined circulating autoantibodies to cultured human bronchial epithelial
      cells (BEAS-2B) in sera from patients with nonallergic asthma by immunoblot
      analysis. IgG autoantibodies to the 49-kD bronchial epithelial cell antigen were
      detected in 10 of 23 patients with nonallergic asthma (43%), 3 of 27 patients
      with allergic asthma (11%), 2 of 20 patients with systemic lupus erythematosus
      (10%), and 3 of 34 healthy volunteers (9%) (p < 0.005). The 49-kD auto-antigen
      was purified and identified as cytokeratin 18 by amino acid sequencing. In this
      study, we identified cytokeratin 18 as a bronchial epithelial autoantigen
      associated with nonallergic asthma. Further studies are needed to determine the
      significance of autoimmunity in nonallergic asthma.

PMID- 12045128
TI  - Lipoxins are potential endogenous antiinflammatory mediators in asthma.
AB  - Lipoxins, endogenous eicosanoids biosynthetized in vivo at inflammation sites,
      are potential antiinflammatory mediators. Subjects with severe asthma present
      chronic inflammation of the airways despite long-term treatment with oral
      glucocorticoids. Therefore it is of interest to investigate the potential
      antiinflammatory effects of lipoxin A4 (LXA4) and lipoxin B4 (LXB4) that could
      attenuate chronic inflammation. In a first time, we detected interleukin (IL)-8
      and LXA4 in supernatants of induced sputum. IL-8 was heightened in severe asthma
      (p = 0.001), whereas high concentrations of lipoxin A4 were present in mild
      asthma (p = 0.001). We then studied the effects of LXA4 on IL-8 released in
      vitro. Nanomolar concentrations of LXA4 and LXB4 inhibited the IL-8 released by
      peripheral blood mononuclear cells from the two groups of patients with asthma: a
      maximal inhibition of 29.4% (p < 0.01) was observed for patients with mild
      asthma, and 41.5% inhibition (p < 0.001) for patients with severe asthma at 1 nM
      and 100 nM LXA4 concentrations, respectively. Polymerase chain reaction analysis
      indicated that peripheral blood mononuclear cells from patients with asthma
      expressed the LXA4 receptor mRNA. Moreover, pertussis toxin reversed LXA4- and
      LXB4-inhibited IL-8 release. These findings suggest that lipoxins have potential
      antiinflammatory action in asthma.

PMID- 12045130
TI  - Interleukin-2-induced increased airway responsiveness and lung Th2 cytokine
      expression occur after antigen challenge through the leukotriene pathway.
AB  - Previous studies have shown that the allergic late airway response (LR) is
      dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same
      model, interleukin-2 (IL-2) has been shown to increase allergic airway responses
      without increasing LT production. This study examined the relationship between
      the upregulation of cellular immunity with IL-2 and the LT pathway in ovalbumin
      sensitized BN rats. Airway responsiveness to LTD(4) was significantly increased
      in BN rats pretreated with IL-2 (20,000 U twice a day for 4.5 days). Treatment
      with montelukast, a cysteinyl LT(1) receptor antagonist, blocked IL-2's induced
      increase of the LR to ovalbumin challenge. When cytokine expression was assessed
      either by semiquantitative polymerase chain reaction or in situ hybridization, we
      found that montelukast decreased the amount of IL-4 mRNA expression in the lungs
      while increasing the amount of interferon-gamma mRNA expression 8 hours after
      challenge. These results indicate that upregulation of cellular immunity with IL
      2 can increase the sensitivity of the airways to LTD(4) and that inhibition of
      the LT pathway will block the LR and modulate cytokine expression after antigen
      challenge.

PMID- 12045131
TI  - Surfactant proteins A and D in children with pulmonary disease due to
      gastroesophageal reflux.
AB  - Children with gastroesophageal reflux often suffer from chronic, severe lung
      damage and recurrent infections. The mechanisms may involve reflux induced lung
      injury with alterations of the surfactant proteins (SP) SP-A and SP-D, which bind
      specifically to various microbes and increase their elimination by granular
      leukocytes and macrophages. In 20 children with gastroesophageal reflux disease
      (GERD) the bronchoalveolar lavage content and macromolecular organization of SP-A
      and SP-D was determined by enzyme linked immunosorbent assay and gel
      chromatography. For comparison, lavages from 17 children without respiratory
      diseases were investigated. Both, SP-A and SP-D were significantly reduced in
      children with GERD-median (25, 75 percentiles) SP-A: 362 (169, 494) ng/ml versus
      867 (656, 1,761) in control subjects and SP-D: 174 (73, 456) ng/ml versus 518
      (295, 748) ng/ml in control subjects. The more active, higher molecular weight
      oligomers of SP-A and especially those of SP-D were diminished, whereas the
      smaller sized forms of SP-D were markedly increased. In children with GERD,
      significantly reduced amounts of SP-A and SP-D and an altered structural
      organization of the surfactant protein oligomers were demonstrated. Such
      impairments of central components of the innate host defense system may
      contribute to the pathogenesis of the chronic lung disease commonly observed in
      these children.

PMID- 12045132
TI  - Acute interstitial pneumonia: comparison of high-resolution computed tomography
      findings between survivors and nonsurvivors.
AB  - This study compared high-resolution computed tomography (CT) findings between 10
      survivors and 21 nonsurvivors of acute interstitial pneumonia and evaluated
      whether the CT findings were predictive of patients' response to treatment. The
      survivor and nonsurvivor groups with pathologically or clinically diagnosed acute
      interstitial pneumonia were similar in age, sex, disease duration, and lung
      injury score. Retrospective, subjective evaluations of the CT scans were
      conducted by two independent observers without knowledge of patient outcomes. CT
      findings were graded on a one to six scale corresponding to consecutive
      pathologic phases as follows: areas of (1) normal attenuation, (2) ground-glass
      attenuation, (3) consolidation, (4) ground-glass attenuation associated with
      traction bronchiolectasis or bronchiectasis, (5) consolidation associated with
      traction bronchiolectasis or bronchiectasis, and (6) honeycombing. An overall
      score was obtained by quantifying the extent of each abnormality in three lung
      zones in each lung. The extent of ground-glass attenuation or consolidation
      associated with traction bronchiolectasis or bronchiectasis was less in survivors
      than nonsurvivors (p = 0.004 and p = 0.009, respectively). Architectural
      distortion was less frequent, and ground-glass attenuation or consolidation
      without traction bronchiolectasis or bronchiectasis was more extensive in
      survivors than in nonsurvivors (p = 0.007, p = 0.002, and p = 0.029,
      respectively). Overall CT scores of survivors were significantly lower than those
      of nonsurvivors (p = 0.0003). A CT score of less than 245 had an 80% positive and
      a 90% negative predictive value for survival. There was good interobserver
      agreement in the assessment of the CT findings (Kappa 0.75). The results indicate
      that CT assessment is potentially helpful in predicting patient prognosis in
      acute interstitial pneumonia regardless of the degree of physiologic abnormality.

PMID- 12045133
TI  - Pulmonary interstitial glycogenosis: a new variant of neonatal interstitial lung
      disease.
AB  - We present the clinical, radiologic, and pathologic findings in lung biopsies
      from seven infants with atypical neonatal lung disease. All seven infants
      presented with tachypnea, hypoxemia, and diffuse interstitial infiltrates with
      overinflated lungs on chest radiographs in the first month of life. Lung biopsies
      from all cases showed similar pathology, with expansion of the interstitium by
      spindle-shaped cells containing periodic acid-Schiff positive diastase labile
      material consistent with glycogen. Immunohistochemical staining showed these
      cells to be vimentin positive but negative for leucocyte common antigen,
      lysozyme, and other macrophage markers. Electron microscopy revealed primitive
      interstitial mesenchymal cells with few cytoplasmic organelles and abundant
      monoparticulate glycogen. Minimal or no glycogen was seen in the alveolar lining
      cells. Five cases were treated with pulse corticosteroids; hydroxychloroquine was
      added in one case. Six of seven infants have shown a favorable clinical outcome.
      One infant died from complications of extreme prematurity and bronchopulmonary
      dysplasia. Three cases that have been followed for at least 6 years have shown
      clinical resolution and radiographic improvement. We propose the term "pulmonary
      interstitial glycogenosis" of the neonate for this new entity to be
      differentiated from other forms of interstitial lung disease. Because abundant
      glycogen is not normally found in pulmonary interstitial cells, we postulate an
      abnormality in lung cytodifferentiation involving interstitial mesenchymal cells.

PMID- 12045134
TI  - Smoking and adult asthma: a healthy smoker effect?

PMID- 12045135
TI  - Volume of airway surface liquid in health and disease.

PMID- 12045136
TI  - No evidence of glucocorticosteroid-induced apoptosis of airway epithelial cells
      In vivo.

PMID- 12045137
TI  - Genomes in motion.

PMID- 12045138
TI  - Race, ethnicity, and genomics: social classifications as proxies of biological
      heterogeneity.
AB  - Over the past century, genetics has experienced a tension between the view that
      racial and ethnic categories are biologically meaningful and the view that these
      social classifications have little or no biological significance. That tension
      continues to inform genomics and is evident in the assembly of biological
      collections and sequence databases that seek to approximate the genetic variation
      found in human populations. Although social identities can be useful and
      convenient proxies of some biological features, for example, in ensuring that
      genomic resources capture a range of genetic variants found in most human
      populations, the ways in which geneticists conceptualize the relationship between
      racial and ethnic identities and genetic variation can be problematic. Inclusion
      of racial and ethnic identifiers in genomic resources can create risks for all
      members of those identified populations and influence lay perceptions of the
      nature of racial and ethnic groups. Thus, the burden of showing the scientific
      utility of racial and ethic identities in the construction and analysis of
      genomic resources falls on researchers. This requires that genetic researchers
      pay as much attention to the social constitution of human populations as
      presently is paid to their genetic composition.

PMID- 12045139
TI  - Compositional gradients in Gramineae genes.
AB  - In this study, we describe a property of Gramineae genes, and perhaps all monocot
      genes, that is not observed in eudicot genes. Along the direction of
      transcription, beginning at the junction of the 5'-UTR and the coding region,
      there are gradients in GC content, codon usage, and amino-acid usage. The
      magnitudes of these gradients are large enough to hinder the annotation of the
      rice genome and to confound the detection of protein homologies across the
      monocot-eudicot divide.

PMID- 12045140
TI  - Fourfold faster rate of genome rearrangement in nematodes than in Drosophila.
AB  - We compared the genome of the nematode Caenorhabditis elegans to 13% of that of
      Caenorhabditis briggsae, identifying 252 conserved segments along their
      chromosomes. We detected 517 chromosomal rearrangements, with the ratio of
      translocations to inversions to transpositions being approximately 1:1:2. We
      estimate that the species diverged 50-120 million years ago, and that since then
      there have been 4030 rearrangements between their whole genomes. Our estimate of
      the rearrangement rate, 0.4-1.0 chromosomal breakages/Mb per Myr, is at least
      four times that of Drosophila, which was previously reported to be the fastest
      rate among eukaryotes. The breakpoints of translocations are strongly associated
      with dispersed repeats and gene family members in the C. elegans genome.

PMID- 12045142
TI  - Pattern of organization of human mitochondrial pseudogenes in the nuclear genome.
AB  - Mitochondrial pseudogenes in the human nuclear genome have been previously
      described, mostly as a source of artifacts during the analysis of the
      mitochondrial genome. With the availability of the complete human genome
      sequence, we performed a comprehensive analysis of mtDNA insertions into the
      nucleus. We found 612 independent integrations that are evenly distributed among
      all chromosomes as well as within each individual chromosome. The identified
      pseudogenes account for a content of at least 0.016% of the human nuclear DNA. Up
      to 30% of a chromosome's mtDNA pseudogene content is composed of fragments that
      encompass two or more adjacent mitochondrial genes, and we found no correlation
      between the abundance of mitochondrial transcripts and the multiplicity of
      integrations. These observations indicate that the migrations of mitochondrial
      DNA sequences to the nucleus were predominantly DNA mediated. Phylogenetic
      analysis of the mtDNA pseudogenes and mtDNA sequences of primates indicate a
      continuous transfer into the nucleus. Because of the limited window of
      opportunity for mtDNA transfer to the germline, sperm mtDNA, which is released
      from degenerating mitochondria after fertilization, could be an important source
      of nuclear mtDNA pseudogenes.

PMID- 12045141
TI  - Multiplex three-dimensional brain gene expression mapping in a mouse model of
      Parkinson's disease.
AB  - To facilitate high-throughput 3D imaging of brain gene expression, a new method
      called voxelation has been developed. Spatially registered voxels (cubes) are
      analyzed, resulting in multiple volumetric maps of gene expression analogous to
      the images reconstructed in biomedical imaging systems. Using microarrays, 40
      voxel images for 9000 genes were acquired from brains of both normal mice and
      mice in which a pharmacological model of Parkinson's disease (PD) had been
      induced by methamphetamine. Quality-control analyses established the
      reproducibility of the voxelation procedure. The investigation revealed a common
      network of coregulated genes shared between the normal and PD brain, and allowed
      identification of putative control regions responsible for these networks. In
      addition, genes involved in cell/cell interactions were found to be prominently
      regulated in the PD brains. Finally, singular value decomposition (SVD), a
      mathematical method used to provide parsimonious explanations of complex data
      sets, identified gene vectors and their corresponding images that distinguished
      between normal and PD brain structures, most pertinently the striatum.

PMID- 12045144
TI  - Tandem repeats in protein coding regions of primate genes.
AB  - Tandem repeats in GenBank primate nucleotide sequences annotated as protein
      coding regions are analyzed. It is found that only trinucleotide repeats show
      repeat enrichment well above the threshold of statistical significance. The
      statistics are improved by a simultaneous search for repeats on both the amino
      acid and nucleotide levels. The results of the analyses of natural sequences are
      interpreted by comparing them with the results of the computer simulation of the
      model dedicated to protein coding regions. According to the simulation results, a
      limited set of trinucleotides, that is, cgg, ccg, cag, and gaa repeats coding for
      polyalanine, polyglycine, polyproline, polyglutamine, and polylysine are prone to
      proliferation. It is also found that within the repeat regions slippage is more
      frequent by a factor of 10 than point mutations, whereas the ratio of silent
      versus recognizable point mutations is approximately the same as elsewhere in
      coding regions. The trinucleotide repeats cover slightly more than 0.3% of the
      protein coding regions of genes.

PMID- 12045145
TI  - Comparison of the small molecule metabolic enzymes of Escherichia coli and
      Saccharomyces cerevisiae.
AB  - The comparison of the small molecule metabolism pathways in Escherichia coli and
      Saccharomyces cerevisiae (yeast) shows that 271 enzymes are common to both
      organisms. These common enzymes involve 384 gene products in E. coli and 390 in
      yeast, which are between one half and two thirds of the gene products of small
      molecule metabolism in E. coli and yeast, respectively. The arrangement and
      family membership of the domains that form all or part of 374 E. coli sequences
      and 343 yeast sequences was determined. Of these, 70% consist entirely of
      homologous domains, and 20% have homologous domains linked to other domains that
      are unique to E. coli, yeast, or both. Over two thirds of the enzymes common to
      the two organisms have sequence identities between 30% and 50%. The remaining
      groups include 13 clear cases of nonorthologous displacement. Our calculations
      show that at most one half to two thirds of the gene products involved in small
      molecule metabolism are common to E. coli and yeast. We have shown that the
      common core of 271 enzymes has been largely conserved since the separation of
      prokaryotes and eukaryotes, including modifications for regulatory purposes, such
      as gene fusion and changes in the number of isozymes in one of the two organisms.
      Only one fifth of the common enzymes have nonhomologous domains between the two
      organisms. Around the common core very different extensions have been made to
      small molecule metabolism in the two organisms.

PMID- 12045143
TI  - Comparative sequence analysis of the X-inactivation center region in mouse,
      human, and bovine.
AB  - We have sequenced to high levels of accuracy 714-kb and 233-kb regions of the
      mouse and bovine X-inactivation centers (Xic), respectively, centered on the Xist
      gene. This has provided the basis for a fully annotated comparative analysis of
      the mouse Xic with the 2.3-Mb orthologous region in human and has allowed a three
      way species comparison of the core central region, including the Xist gene. These
      comparisons have revealed conserved genes, both coding and noncoding, conserved
      CpG islands and, more surprisingly, conserved pseudogenes. The distribution of
      repeated elements, especially LINE repeats, in the mouse Xic region when compared
      to the rest of the genome does not support the hypothesis of a role for these
      repeat elements in the spreading of X inactivation. Interestingly, an asymmetric
      distribution of LINE elements on the two DNA strands was observed in the three
      species, not only within introns but also in intergenic regions. This feature is
      suggestive of important transcriptional activity within these intergenic regions.
      In silico prediction followed by experimental analysis has allowed four new
      genes, Cnbp2, Ftx, Jpx, and Ppnx, to be identified and novel, widespread,
      complex, and apparently noncoding transcriptional activity to be characterized in
      a region 5' of Xist that was recently shown to attract histone modification early
      after the onset of X inactivation.

PMID- 12045146
TI  - Genomic evolution of the long terminal repeat retrotransposons in
      hemiascomycetous yeasts.
AB  - We identified putative long terminal repeat- (LTR) retrotransposon sequences
      among the 50,000 random sequence tags (RSTs) obtained by the Genolevures project
      from genomic libraries of 13 Hemiascomycetes species. In most cases additional
      sequencing enabled us to assemble the whole sequences of these retrotransposons.
      These approaches identified 17 distinct families, 10 of which are defined by full
      length elements. We also identified five families of solo LTRs that were not
      associated with retrotransposons. Ty1-like retrotransposons were found in four of
      five species that are phylogenetically related to Saccharomyces cerevisiae (S.
      uvarum, S. exiguus, S. servazzii, and S. kluyveri but not Zygosaccharomyces
      rouxii), and in two of three Kluyveromyces species (K. lactis and K. marxianus
      but not K. thermotolerans). Only multiply crippled elements could be identified
      in the K. lactis and S. servazzii strains analyzed, and only solo LTRs could be
      identified in S. uvarum. Ty4-like elements were only detected in S. uvarum,
      indicating that these elements appeared recently before speciation of the
      Saccharomyces sensu stricto species. Ty5-like elements were detected in S.
      exiguus, Pichia angusta, and Debaryomyces hansenii. A retrotransposon homologous
      with Tca2 from Candida albicans, an element absent from S. cerevisiae, was
      detected in the closely related species D. hansenii. A complete Ty3/gypsy element
      was present in S. exiguus, whereas only partial, often degenerate, sequences
      resembling this element were found in S. servazzii, Z. rouxii, S. kluyveri, C.
      tropicalis, and Yarrowica lipolytica. P. farinosa (syn. P. sorbitophila) is
      currently the only yeast species in which no LTR retrotransposons or remnants
      have been found. Thorough analysis of protein sequences, structural
      characteristics of the elements, and phylogenetic relationships deduced from
      these data allowed us to propose a classification for the Ty1/copia elements of
      hemiascomycetous yeasts and a model of LTR-retrotransposon evolution in yeasts.

PMID- 12045147
TI  - Shannon information theoretic computation of synonymous codon usage biases in
      coding regions of human and mouse genomes.
AB  - Exonic GC of human mRNA reference sequences (RefSeqs), as well as A, C, G, and T
      in codon position 3 are linearly correlated with genomic GC. These observations
      utilize information from the completed human genome sequence and a large, high
      quality set of human and mouse coding sequences, and are in accord with similar
      determinations published by others. A Shannon Information Theoretic measure of
      bias in synonymous codon usage was developed. When applied to either human or
      mouse RefSeqs, this measure is nonlinearly correlated with genomic, exonic, and
      third codon position A, C, G, and T. Information values between orthologous mouse
      and human RefSeqs are linearly correlated: mouse = 0.092 + 0.55 human. Mouse
      genes were consistently placed in genomic regions whose GC content was closer to
      50% than was the GC content of the human ortholog. Since the (nonlinear)
      information versus percent GC curve has a minimum at 50% GC and monotonically
      increases with increasing distance from 50% GC, this phenomenon directly results
      in the low slope of 0.55. This appears to be a manifestation of an evolutionary
      strategy for placement of genes in regions of the genome with a GC content that
      relates synonymous codon bias and protein folding.

PMID- 12045148
TI  - Extended intermarker linkage disequilibrium in the Afrikaners.
AB  - In this study we conducted an investigation of the background level of linkage
      disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness
      of this genetic isolate for mapping complex traits. We analyzed intermarker LD in
      62 nuclear families using microsatellite markers covering extended chromosomal
      regions. The markers were selected to allow the first direct comparison of long
      range LD in the Afrikaners to LD in other demographic groups. Using several
      statistical measures, we find significant evidence for LD in the Afrikaners
      extending remarkably over a 6-cM range. In contrast, LD decays significantly
      beyond 3-cM distances in the other founder and outbred populations examined. This
      study strongly supports the appropriateness of the Afrikaner population for
      genome-wide scans that exploit LD to map common, multigenic disorders.

PMID- 12045149
TI  - Essential genes are more evolutionarily conserved than are nonessential genes in
      bacteria.
AB  - The "knockout-rate" prediction holds that essential genes should be more
      evolutionarily conserved than are nonessential genes. This is because negative
      (purifying) selection acting on essential genes is expected to be more stringent
      than that for nonessential genes, which are more functionally dispensable and/or
      redundant. However, a recent survey of evolutionary distances between
      Saccharomyces cerevisiae and Caenorhabditis elegans proteins did not reveal any
      difference between the rates of evolution for essential and nonessential genes.
      An analysis of mouse and rat orthologous genes also found that essential and
      nonessential genes evolved at similar rates when genes thought to evolve under
      directional selection were excluded from the analysis. In the present study, we
      combine genomic sequence data with experimental knockout data to compare the
      rates of evolution and the levels of selection for essential versus nonessential
      bacterial genes. In contrast to the results obtained for eukaryotic genes,
      essential bacterial genes appear to be more conserved than are nonessential genes
      over both relatively short (microevolutionary) and longer (macroevolutionary)
      time scales.

PMID- 12045150
TI  - A bioinformatics-based strategy identifies c-Myc and Cdc25A as candidates for the
      Apmt mammary tumor latency modifiers.
AB  - The epistatically interacting modifier loci (Apmt1 and Apmt2) accelerate the
      polyoma Middle-T (PyVT)-induced mammary tumor. To identify potential candidate
      genes loci, a combined bioinformatics and genomics strategy was used. On the
      basis of the assumption that the loci were functioning in the same or
      intersecting pathways, a search of the literature databases was performed to
      identify molecular pathways containing genes from both candidate intervals. Among
      the genes identified by this method were the cell cycle-associated genes Cdc25A
      and c-Myc, both of which have been implicated in breast cancer. Genomic
      sequencing revealed noncoding polymorphism in both genes, in the promoter region
      of Cdc25A, and in the 3' UTR of c-Myc. Molecular and in vitro analysis showed
      that the polymorphisms were functionally significant. In vivo analysis was
      performed by generating compound PyVT/Myc double-transgenic animals to mimic the
      hypothetical model, and was found to recapitulate the age-of-onset phenotype.
      These data suggest that c-Myc and Cdc25A are Apmt1 and Apmt2, and suggest that,
      at least in certain instances, bioinformatics can be utilized to bypass congenic
      construction and subsequent mapping in conventional QTL studies.

PMID- 12045151
TI  - A highly reproducible, linear, and automated sample preparation method for DNA
      microarrays.
AB  - DNA microarrays are powerful tools to detect changes in transcript abundance in
      multiple samples in parallel. However, detection of differential transcript
      levels requires a reproducible sample (target) preparation method in addition to
      a high-performance microarray. Therefore, we optimized a target-preparation
      method that converts the poly(A)(+) RNA fraction of total RNA into complementary
      DNA, then generates biotin-labeled complementary RNA from the cDNA. We measured
      the efficiency of incorporation of biotin-containing nucleotides by an enzymatic
      digestion, followed by resolution via analytical high-performance liquid
      chromatography (HPLC). When the target was hybridized to a sensitive and
      reproducible microarray platform, low coefficients of variation in both
      hybridization intensities and differential expression ratios across target
      preparations were observed. Nearly identical hybridization intensities and
      expression ratios are observed regardless of whether poly(A)(+)-enriched RNA or
      total RNA is used as the starting material. We show the ability to discern
      biological and production variability through the use of different lots of
      commercial samples as visualized by hierarchical clustering. Automation of the
      target-preparation procedure shows equivalence to the manual procedure,
      reproducible yields of target, and low variability as measured by hybridization
      to microarrays. Most importantly, RNA mixing experiments show a linear and
      quantitative amplification in probe hybridization signals for >6000 genes across
      the entire signal range.

PMID- 12045152
TI  - An integrated computational and laboratory approach for selective amplification
      of mRNAs containing the adenylate uridylate-rich element consensus sequence.
AB  - Messenger RNAs that have the stability determinants, adenylate uridylate-rich
      elements (AREs), in their 3' untranslated region (UTR) code for key products that
      regulate early and transient biological responses. We used a computational
      laboratory approach for amplification of large, including full-length, protein
      coding regions for ARE genes. Statistical analysis of the initiation regions in
      the 5' UTR of ARE-mRNAs was performed. Accordingly, several 5' primers and a
      single universal 3' primer that targeted the initiation consensuses and ARE
      regions, respectively, were designed. Using optimized conditions, the primers
      were able to enrich and amplify large protein-coding regions for the ARE gene
      family. The selective amplification of ARE cDNAs was verified using specific
      polymerase chain reactions (PCRs) to known ARE mRNA molecules and monitoring the
      abundance of the non-ARE beta-actin signal. A mini-library from the amplified ARE
      products was constructed for further confirmation of ARE selection. Distinct ARE
      amplified cDNA pools were selectively generated by distinct 5' primers. The
      biological utility of the method was shown with differential display. The up
      regulation of several ARE-mRNAs, including the full-length coding region of the
      small inducible cytokine A4 (SCYA4) gene, was shown in endotoxin-stimulated
      monocytic cells. The integrated computational and laboratory approach should lead
      to enhanced capability for discovery and expression analysis of early and
      transient response genes.

PMID- 12045153
TI  - The human genome browser at UCSC.
AB  - As vertebrate genome sequences near completion and research refocuses to their
      analysis, the issue of effective genome annotation display becomes critical. A
      mature web tool for rapid and reliable display of any requested portion of the
      genome at any scale, together with several dozen aligned annotation tracks, is
      provided at http://genome.ucsc.edu. This browser displays assembly contigs and
      gaps, mRNA and expressed sequence tag alignments, multiple gene predictions,
      cross-species homologies, single nucleotide polymorphisms, sequence-tagged sites,
      radiation hybrid data, transposon repeats, and more as a stack of coregistered
      tracks. Text and sequence-based searches provide quick and precise access to any
      region of specific interest. Secondary links from individual features lead to
      sequence details and supplementary off-site databases. One-half of the annotation
      tracks are computed at the University of California, Santa Cruz from publicly
      available sequence data; collaborators worldwide provide the rest. Users can
      stably add their own custom tracks to the browser for educational or research
      purposes. The conceptual and technical framework of the browser, its underlying
      MYSQL database, and overall use are described. The web site currently serves over
      50,000 pages per day to over 3000 different users.

PMID- 12045156
TI  - Sudden death predictors: an inflammatory association.

PMID- 12045157
TI  - Myocardial infarct: no one size fits all.

PMID- 12045158
TI  - Patent foramen ovale and recurrent stroke: another paradoxical twist.

PMID- 12045159
TI  - Inflammatory biomarkers, statins, and the risk of stroke: cracking a clinical
      conundrum.

PMID- 12045160
TI  - Cardiology patient page. Restenosis: repeat narrowing of a coronary artery:
      prevention and treatment.

PMID- 12045161
TI  - Circulatory support for long-term treatment of heart failure: experience with an
      intraventricular continuous flow pump.
AB  - BACKGROUND: A lifetime mechanical solution for advanced heart failure must be
      reliable, with a low risk of life-threatening complications. After extensive
      laboratory testing, we began clinical trials with an axial flow pump for long
      term treatment of New York Heart Association class IV, transplant-ineligible
      patients. METHODS AND RESULTS: The Jarvik 2000 is a continuous flow device that
      is implanted in the apex of the left ventricle with offloading to the descending
      thoracic aorta. Skull-based percutaneous power delivery was derived from cochlear
      implant technology. We used this system in 4 patients with end-stage dilated
      cardiomyopathy. Exercise capacity, quality of life, device parameters, and native
      heart function were monitored serially. One patient died from right heart failure
      at 3 months. The other patients were discharged from hospital between 3 and 8
      weeks postoperatively and are currently New York Heart Association I or II.
      Follow-up lasted between 9 and 20 months. There has been no device failure or
      hemolysis. Native heart function and quality of life were markedly improved.
      CONCLUSIONS: The Jarvik 2000 is a true assist (rather than replacement) device
      that functions synergistically with the native left ventricle and provides
      excellent quality of life. Adverse events are infrequent. This blood pump may
      provide a mechanical solution for end-stage heart failure in the community.

PMID- 12045162
TI  - Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia.
AB  - BACKGROUND: Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward
      rectifying K+ channels (Kir2.1), produce Andersen's syndrome, which is
      characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features.
      METHODS AND RESULTS: In 3 Japanese family members with periodic paralysis,
      ventricular arrhythmias, and marked QT prolongation, polymerase chain
      reaction/single-strand conformation polymorphism/DNA sequencing identified a
      novel, heterozygous, missense mutation in KCNJ2, Thr192Ala (T192A), which was
      located in the putative cytoplasmic chain after the second transmembrane region
      M2. Using the Xenopus oocyte expression system, we found that the T192A mutant
      was nonfunctional in the homomeric condition. Coinjection with the wild-type gene
      reduced the current amplitude, showing a weak dominant-negative effect.
      CONCLUSIONS: T192, which is located in the phosphatidylinositol-4,5-bisphosphate
      binding site and also the region necessary for Kir2.1 multimerization, is a
      highly conserved amino acid residue among inward-rectifier channels. We suggest
      that the T192A mutation resulted in the observed electrical phenotype.

PMID- 12045163
TI  - Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as
      predictors of sudden cardiac death.
AB  - BACKGROUND: Sudden cardiac death (SCD) is an important cause of mortality even
      among apparently healthy populations. However, our ability to identify those at
      risk for SCD in the general population is poor, and more specific markers are
      needed. METHODS AND RESULTS: To compare and contrast the relative importance of C
      reactive protein (CRP), homocysteine, and lipids as long-term predictors of SCD,
      we performed a prospective, nested, case-control analysis involving 97 cases of
      SCD among apparently healthy men enrolled in the Physician's Health Study. Of
      these plasma markers measured, only baseline CRP levels were significantly
      associated with the risk of SCD over the ensuing 17 years of follow-up (P for
      trend=0.001). The increase in risk associated with CRP levels was primarily seen
      among men in the highest quartile, who were at a 2.78-fold increased risk of SCD
      (95% CI 1.35 to 5.72) compared with men in the lowest quartile. These results
      were not significantly altered in analyses that (in addition to the matching
      variables of age and smoking status) controlled for lipid parameters,
      homocysteine, and multiple cardiac risk factors (relative risk for highest versus
      lowest quartile 2.65, 95% CI 0.79 to 8.83; P for trend=0.03). In contrast to the
      positive relationship observed for CRP, neither homocysteine nor lipid levels
      were significantly associated with risk of SCD. CONCLUSIONS: These prospective
      data suggest that CRP levels may be useful in identifying apparently healthy men
      who are at an increased long-term risk of SCD.

PMID- 12045164
TI  - Prevention of inflammation-induced endothelial dysfunction: a novel vasculo
      protective action of aspirin.
AB  - BACKGROUND: Inflammation and infection may initiate and promote atherosclerosis
      or its complications by adverse effects on the vascular endothelium. The
      mechanisms by which aspirin reduces cardiovascular risk might involve anti
      inflammatory actions or direct effects on the endothelium in addition to its
      antiplatelet action. We investigated the role of aspirin in modulating
      endothelial dysfunction induced by an experimental inflammatory stimulus. METHODS
      AND RESULTS: An inflammatory response was generated in healthy volunteers by
      Salmonella typhi vaccination. Venous occlusion plethysmography was used to assess
      resistance vessel responses (16 hours before and 8 hours after vaccination) to
      the endothelium-dependent dilator bradykinin (BK) and the endothelium-independent
      dilator glyceryl-trinitrate (GTN). Twelve subjects were randomized to receive
      either aspirin 1.2 g orally or placebo 2 hours before vaccination. After
      vaccination alone there was suppression of the response to BK in the placebo
      group (P=0.01), with no change in response to GTN. In the aspirin group there was
      no change in the response to either BK or GTN after vaccination. Aspirin
      treatment prevented vaccine-induced elevation of interleukin-1 receptor
      antagonist but enhanced the generation of tumor necrosis factor-alpha compared
      with placebo. In an additional 5 individuals, local intrabrachial aspirin (10
      mg/min for 15 minutes) failed to restore responses to BK after vaccination.
      CONCLUSIONS: Experimental inflammation produces endothelial dysfunction, which
      can be prevented by pretreatment with aspirin. Locally administered aspirin does
      not reverse vaccine-induced endothelial dysfunction once established. The
      protective effects of aspirin on inflammation-induced endothelial dysfunction may
      be through modulation of the cytokine cascade.

PMID- 12045154
TI  - A subtracted cDNA library from the zebrafish (Danio rerio) embryonic inner ear.
AB  - A database was built that consists of 4694 sequence contigs of approximately
      18,000 reads of cDNAs isolated from the microdissected otocysts of zebrafish
      embryos at 20-30 hour postfertilization, following subtraction with a pool of
      liver cDNAs from adult fish. These sequences were compared with those of public
      databanks. Significant similarity were recorded and organized in a relational
      database at http://www.genoscope.cns.fr/zie. A first group of 2067 sequences
      correspond to 1428 known zebrafish genes or ESTs present in the Danio rerio
      section of UniGene. A second group of 302 sequences encode putative proteins that
      showed significant similarity (50%-100%) with 302 nonzebrafish proteins in the nr
      databank, a public databank containing an exhaustive nonredundant collection of
      protein sequences from different species
      (ftp://ftp.ncbi.nlm.nih.gov/blast/db/nr). The remaining 2325 (49.5%) sequence
      contigs or singletons showed no significant similarity with sequences available
      in public databanks. Several genes known to be expressed in the developing inner
      ear were represented in the present database, in particular genes involved in
      hair cell differentiation or innervation The occurrence of these genes validates
      the outcome of this study as the first collection of ESTs preferentially
      expressed in the zebrafish inner ear during the period of hair cell
      differentiation and neuroblast delamination from the otic vesicle epithelium.
      Novel zebrafish genes also involved in these processes are thus likely to be
      represented among the sequences obtained herein, for which no homology was found
      in the D. rerio section of UniGene. [The sequence data from this study have been
      submitted to EMBL under accession nos. AL714032-AL731531].

PMID- 12045165
TI  - Heterogeneity in the management and outcomes of patients with acute myocardial
      infarction complicated by heart failure: the National Registry of Myocardial
      Infarction.
AB  - BACKGROUND: Heart failure (HF) is an important predictor of poor outcome after
      acute myocardial infarction (AMI). However, limited data exist about the clinical
      significance of HF in the coronary reperfusion era and the impact of its timing
      on hospital outcomes. The objective of this study was to determine the clinical
      impact of HF complicating AMI in the National Registry of Myocardial Infarction
      (NRMI). A secondary objective was to determine differences in demographic and
      clinical characteristics, treatment, and hospital death rates in patients
      presenting with HF compared with those developing HF after presentation. METHODS
      AND RESULTS: The study sample consisted of patients with AMI and without a
      history of HF included in the NRMI. Of 606 500 cases included from July 1, 1994
      to June 30, 2000, 123 938 (20.4%) patients had HF at the time of hospital
      presentation and 52 220 (8.6%) developed HF thereafter. Patients with HF were
      older, more likely female, had more comorbidities, and were less likely to
      receive effective cardiac medications compared with patients without HF. The
      multivariable adjusted odds for in-hospital death were higher for patients with
      HF at presentation and thereafter (3.1 and 5.5, respectively) than those without
      HF. CONCLUSIONS: Results from this nationwide registry suggest that the incidence
      and hospital death rates associated with HF complicating AMI remain high.
      Patients developing HF after hospital admission are at even greater risk than
      those presenting with HF. Effective cardiac therapies remain underutilized in
      these patients, and the reasons for this underutilization need to be explored.

PMID- 12045166
TI  - Celiac disease associated with autoimmune myocarditis.
AB  - BACKGROUND: Both celiac disease (CD) and myocarditis can be associated with
      systemic autoimmune disorders; however, the coexistence of the 2 entities has
      never been investigated, although its identification may have a clinical impact.
      METHODS AND RESULTS: We screened the serum of 187 consecutive patients with
      myocarditis (118 males and 69 females, mean age 41.7+/-14.3 years) for the
      presence of cardiac autoantibodies, anti-tissue transglutaminase (IgA-tTG), and
      anti-endomysial antibodies (AEAs). IgA-tTG-positive and AEA-positive patients
      underwent duodenal endoscopy and biopsy and HLA analysis. Thirteen of the 187
      patients were positive for IgA-tTG, and 9 (4.4%) of them were positive for AEA.
      These 9 patients had iron-deficient anemia and exhibited duodenal endoscopic and
      histological evidence of CD. CD was observed in 1 (0.3%) of 306 normal controls
      (P<0.003). In CD patients, myocarditis was associated with heart failure in 5
      patients and with ventricular arrhythmias (Lown class III-IVa) in 4 patients.
      From histological examination, a lymphocytic infiltrate was determined to be
      present in 8 patients, and giant cell myocarditis was found in 1 patient;
      circulating cardiac autoantibodies were positive and myocardial viral genomes
      were negative in all patients. HLA of the patients with CD and myocarditis was
      DQ2-DR3 in 8 patients and DQ2-DR5(11)/DR7 in 1 patient. The 5 patients with
      myocarditis and heart failure received immunosuppression and a gluten-free diet,
      which elicited recovery of cardiac volumes and function. The 4 patients with
      arrhythmia, after being put on a gluten-free diet alone, showed improvement in
      the arrhythmia (Lown class I). CONCLUSIONS: A common autoimmune process toward
      antigenic components of the myocardium and small bowel can be found in >4% of the
      patients with myocarditis. In these patients, immunosuppression and a gluten-free
      diet can be effective therapeutic options.

PMID- 12045167
TI  - Effects of xanthine oxidase inhibition with allopurinol on endothelial function
      and peripheral blood flow in hyperuricemic patients with chronic heart failure:
      results from 2 placebo-controlled studies.
AB  - BACKGROUND: In patients with chronic heart failure (CHF), hyperuricemia is a
      common finding and is associated with reduced vasodilator capacity and impaired
      peripheral blood flow. It has been suggested that the causal link of this
      association is increased xanthine oxidase (XO)-derived oxygen free radical
      production and endothelial dysfunction. We therefore studied the effects of XO
      inhibition with allopurinol on endothelial function and peripheral blood flow in
      CHF patients after intra-arterial infusion and after oral administration in 2
      independent placebo-controlled studies. METHODS AND RESULTS: In 10 CHF patients
      with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with
      elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion)
      and endothelium-independent (nitroglycerin infusion) vasodilation of the radial
      artery was determined. Coinfusion of allopurinol (600 microg/min) improved
      endothelium-dependent but not endothelium-independent vasodilation in
      hyperuricemic patients (P<0.05). In a double-blind, crossover design,
      hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or
      placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743
      micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean
      reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol
      improved peak blood flow (venous occlusion plethysmography) in arms (+24%,
      P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms
      (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by
      20% after allopurinol treatment (P<0.001). There was a direct relation between
      change of UA and improvement of flow-dependent flow after allopurinol treatment
      (r=0.63, P<0.05). CONCLUSIONS: In hyperuricemic CHF patients, XO inhibition with
      allopurinol improves peripheral vasodilator capacity and blood flow both locally
      and systemically.

PMID- 12045168
TI  - Effect of medical treatment in stroke patients with patent foramen ovale: patent
      foramen ovale in Cryptogenic Stroke Study.
AB  - BACKGROUND: Patent foramen ovale (PFO) is associated with stroke, but there are
      no randomized studies to evaluate the efficacy of antithrombotic therapies.
      METHODS AND RESULTS: The PFO in Cryptogenic Stroke Study was a 42-center study
      that evaluated transesophageal echocardiographic findings in patients randomly
      assigned to warfarin or aspirin in the Warfarin-Aspirin Recurrent Stroke Study.
      In this study, 630 stroke patients were enrolled, of whom 312 (49.5%) were
      randomized to warfarin and 318 (50.5%) to aspirin. Of these, 265 patients
      experienced cryptogenic stroke and 365 experienced known stroke subtypes. End
      points were recurrent ischemic stroke or death. PFO was present in 203 patients
      (33.8%). There was no significant difference in the time to primary end points
      between those with and those without PFO in the overall population (P=0.84;
      hazard ratio 0.96; 95% CI 0.62 to 1.48; 2-year event rates 14.8% versus 15.4%) or
      in the cryptogenic subset (P=0.65; hazard ratio 1.17; 95% CI 0.60 to 2.37; 2-year
      event rates 14.3% versus 12.7%). There was no significant difference among those
      with no, small, or large PFO (P=0.41 for small PFO and P=0.16 for large PFO; 2
      year event rates for no, small, and large PFO, 15.4%, 18.5%, and 9.5%,
      respectively). There was no significant difference between patients with isolated
      PFO and those with PFO in association with atrial septal aneurysm (P=0.84; 2-year
      event rates 14.5% versus 15.9%). In patients with PFO, there was no significant
      difference in the time to primary end points between those treated with warfarin
      and those treated with aspirin (P=0.49; hazard ratio 1.29; 95% CI 0.63 to 2.64; 2
      year event rates 16.5% versus 13.2%). CONCLUSIONS: On medical therapy, the
      presence of PFO in stroke patients did not increase the chance of adverse events
      regardless of PFO size or the presence of atrial septal aneurysm.

PMID- 12045169
TI  - Effects of cholesterol and inflammation-sensitive plasma proteins on incidence of
      myocardial infarction and stroke in men.
AB  - BACKGROUND: Although cholesterol is a major cardiovascular risk factor, its
      association with stroke remains controversial. This study explored whether the
      cholesterol-related incidence of stroke and myocardial infarction is modified by
      plasma markers of inflammation in a large, population-based cohort with a long
      follow-up. METHODS AND RESULTS: Plasma cholesterol and 5 inflammation-sensitive
      plasma proteins (ISP) (fibrinogen, alpha1-antitrypsin, haptoglobin,
      ceruloplasmin, and orosomucoid) were determined in 6063 healthy men, 28 to 61
      years of age. The incidence of stroke, cardiac events (fatal and nonfatal), and
      cardiovascular deaths was compared between groups defined by levels of
      cholesterol and ISP. Mean follow-up was 18.7 years. High ISP level was defined as
      2 to 5 ISP in the top quartile. High cholesterol was associated with higher
      levels of ISP. Hypercholesterolemia (> or =6.5 mmol/L, 251 mg/dL) was associated
      with an increased incidence of ischemic stroke and cardiac events and with a
      reduced incidence of intracerebral hemorrhage. The ISP levels modified these
      associations. After risk factor adjustment, men with hypercholesterolemia and
      high ISP levels had a significantly higher risk of cardiovascular death (relative
      risk [RR]=2.4; CI, 1.8 to 3.3), cardiac events (RR=2.3; CI, 1.8 to 3.0), and
      ischemic stroke (RR=2.1; CI, 1.4 to 3.3) than men with normal cholesterol and low
      ISP levels. In the absence of high ISP levels, hypercholesterolemia was
      associated with a moderately higher risk of cardiovascular death (RR=1.4; CI, 1.0
      to 2.0) and cardiac events (RR=1.5; CI, 1.2 to 1.9) but not significantly with
      ischemic stroke (RR=1.25; CI, 0.8 to 2.0). CONCLUSIONS: Hypercholesterolemia is
      associated with high plasma levels of ISP. These proteins increase the
      cholesterol-related incidence of cardiovascular diseases. In the absence of
      elevated ISP levels, no statistically confirmed association was found between
      hypercholesterolemia and ischemic stroke.

PMID- 12045170
TI  - Serum elastase activity, serum elastase inhibitors, and occurrence of carotid
      atherosclerotic plaques: the Etude sur le Vieillissement Arteriel (EVA) study.
AB  - BACKGROUND: In the last decades, interest has increased in the potential
      deleterious atherogenic effects of some cellular elastase activities. The results
      of experimental and clinical investigations were inconsistent. In this report, we
      assessed the associations of serum elastase activity and serum elastase
      inhibitors with carotid plaque occurrence during the 4-year follow-up in a
      population of 859 subjects free of coronary heart disease and stroke (age, 59 to
      71 years). METHODS AND RESULTS: Serum elastase activity and serum elastase
      inhibitors were measured at baseline examination. Carotid B-mode ultrasound
      examination was performed at baseline and 2 years and 4 years later. The
      occurrence of carotid plaques in subjects with the lowest serum elastase activity
      values (quartile 1), in those with the intermediate values (quartiles 2 to 3),
      and in those with the highest values (quartile 4) was, respectively, 24.6%,
      18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid
      plaque occurrence associated with the three groups (adjusted for major known
      cardiovascular risk factors) were, respectively, 1.00, 0.67 (CI, 0.44 to 1.02;
      P<0.06), and 0.40 (CI, 0.23 to 0.70, P<0.001). For serum elastase inhibitors, the
      occurrence of carotid plaques in quartile 1 (lowest values), quartiles 2 to 3,
      and quartile 4 (highest values) was, respectively, 11.7%, 18.8%, and 25.2% (P for
      trend<0.001). The corresponding multivariate adjusted odds ratios were 1.00, 1.98
      (CI, 1.19 to 3.31, P<0.01), and 3.18 (CI, 1.80 to 5.60, P<0.001). CONCLUSIONS:
      Low values of serum elastase activity and high values of serum elastase
      inhibitors were strongly and independently associated with increased 4-year
      carotid plaque occurrence. Further studies are necessary to elucidate the nature
      of the associations between elastase parameters and atherosclerosis.

PMID- 12045171
TI  - Roxithromycin treatment prevents progression of peripheral arterial occlusive
      disease in Chlamydia pneumoniae seropositive men: a randomized, double-blind,
      placebo-controlled trial.
AB  - BACKGROUND: Evidence has been provided that the atherosclerotic process may be
      associated with chronic infection with Chlamydia pneumoniae. The effect of
      antibiotic treatment on peripheral arterial occlusive disease has not been
      investigated yet. METHODS AND RESULTS: Forty C pneumoniae seropositive men
      suffering from peripheral arterial occlusive disease were randomly assigned to
      receive either roxithromycin (300 mg daily) or placebo for 28 days. During the
      2.7-year follow-up, the number of invasive revascularizations per patient, the
      walking distance before intervention (in patients without intervention at study
      end), and the change of carotid plaque size were assessed. Five interventions
      were performed on 4 patients (20%) in the roxithromycin group, and 29
      interventions were performed on 9 patients (45%) in the placebo group. Limitation
      of walking distance to 200 m or less was observed in 4 patients (20%) in the
      roxithromycin group and in 13 patients (65%) in the placebo group. The effect of
      macrolide treatment on the number of interventions per patient and on
      preinterventional walking distance was significant. Possible confounding
      variables such as classical vascular risk factors were excluded by multiple
      regression analyses. Carotid plaque areas monitored over 6 months decreased in
      the roxithromycin group (mean relative value, 94.4%) but remained constant in the
      placebo group (100.2%). Regression of carotid plaque size observed in
      roxithromycin-treated patients was significant for soft plaques. CONCLUSIONS:
      This study indicates that macrolide treatment for 1 month is effective in
      preventing C pneumoniae seropositive men from progression of lower limb
      atherosclerosis for several years.

PMID- 12045172
TI  - Steroid receptor coactivator-3 is required for inhibition of neointima formation
      by estrogen.
AB  - BACKGROUND: The vasoprotective effects of estrogen are mediated by estrogen
      receptors (ERs). ERs are transcription factors that require coactivators to exert
      transcriptional activity. The steroid receptor coactivator-3 (SRC-3, also known
      as pCIP, AIB1, ACTR, and TRAM-1) interacts with estrogen-bound ERs and strongly
      coactivates the transcription of target genes in cultured cells. This study has
      characterized the expression of SRC-3 in cardiovascular tissue and the role of
      SRC-3 in estrogen-dependent vasoprotection from vascular injury. METHODS AND
      RESULTS: Phenotypically normal SRC-3(+/-) mice with a knock-in LacZ reporter were
      used to characterize SRC-3 expression by X-gal staining within the cardiovascular
      system. Staining signals were specifically detected in vascular smooth muscle
      cells and endothelial cells but not in myocardial cells. The role of SRC-3 during
      vascular remodeling was analyzed using a unilateral carotid ligation model. The
      extent of neointima formation in SRC-3(-/-) mice was significantly higher than in
      wild-type mice, and this difference was diminished after depletion of estrogen by
      ovariectomy. After ovariectomy, neointimal growth in wild-type mice was almost
      completely inhibited by estrogen treatment but only partially inhibited in SRC-3(
      /-) mice. Furthermore, estrogen treatment resulted in reduced inhibition of
      intimal cell proliferation in SRC-3(-/-) mice. CONCLUSIONS: SRC-3 is highly
      expressed in vascular smooth muscle cells and endothelial cells. The loss of SRC
      3 function causes a decrease in sensitivity of estrogen-mediated inhibition of
      neointimal growth, which may be attributable to an insufficient suppression of
      vascular cell proliferation. These results indicate that SRC-3 largely
      facilitates ER-dependent vasoprotective effects under conditions of vascular
      trauma.

PMID- 12045174
TI  - Diazoxide opens the mitochondrial permeability transition pore and alters Ca2+
      transients in rat ventricular myocytes.
AB  - BACKGROUND: The mitochondrial K(ATP) channel (mitoK(ATP)) has been implicated as
      an end effector or trigger of ischemic preconditioning (IP). Although a
      mitoK(ATP) opener, diazoxide, mimics IP, mechanisms for the cardioprotective
      action remain unclear. METHODS AND RESULTS: We measured Ca2+ transients (CaTs)
      and mitochondrial inner membrane potential (Deltapsi(m)) with confocal microscopy
      and the fluorescent probes fluo-4 and tetramethylrhodamine ethyl ester
      perchlorate in rat ventricular myocytes. Diazoxide increased the amplitudes and
      diastolic levels of CaTs dose dependently. The effects of diazoxide on CaTs were
      inhibited by the mitoK(ATP) antagonist sodium 5-hydroxydecanoic acid (100
      micromol/L), whereas application of diazoxide caused little change in
      Deltapsi(m). After sarcoplasmic reticulum function was disabled with ryanodine
      and thapsigargin, the effects of diazoxide on CaTs were still observed. The
      opening of the mitochondrial permeability transition pore was monitored with
      fluorescent calcein. Diazoxide accelerated the leakage of calcein from
      mitochondrial matrix (16% of control; P<0.05), and this effect was inhibited by
      cyclosporin A (2 micromol/L). Cyclosporin A also abolished the effects of
      diazoxide on CaTs. Diazoxide oxidized flavoprotein fluorescence reversibly, and
      this effect was partially blunted by cyclosporin A (by 24%; P<0.05). CONCLUSIONS:
      We conclude that in rat ventricular myocytes, diazoxide modulates the opening of
      the mitochondrial permeability transition pore, resulting in an increase in CaTs
      independent of the changes in Deltapsi(m). The action of diazoxide on the
      mitochondrial permeability transition pore also affects the mitochondrial redox
      state.

PMID- 12045173
TI  - Atorvastatin inhibits hypercholesterolemia-induced cellular proliferation and
      bone matrix production in the rabbit aortic valve.
AB  - BACKGROUND: Despite the common occurrence of aortic stenosis, the cellular causes
      of the disorder are unknown, in part because of the absence of experimental
      models. We hypothesized that atherosclerosis and early bone matrix expression in
      the aortic valve occurs secondary to experimental hypercholesterolemia and that
      treatment with atorvastatin modifies this transformation. METHODS AND RESULTS: To
      test this hypothesis, we developed an experimental hypercholesterolemic rabbit
      model. New Zealand White rabbits (n=48) were studied: group 1 (n=16), normal
      diet; group 2 (n=16), 1% (wt/wt) cholesterol diet; and group 3 (n=16), 1% (wt/wt)
      cholesterol diet plus atorvastatin (3 mg/kg per day). The aortic valves were
      examined with hematoxylin and eosin stain, Masson trichrome, macrophage (RAM 11),
      proliferation cell nuclear antigen (PCNA), and osteopontin immunostains.
      Cholesterol and highly sensitive C-reactive protein (hsCRP) serum levels were
      obtained by standard assays. Computerized morphometry and digital image analysis
      were performed for quantifying PCNA (% area). Electron microscopy and immunogold
      labeling were performed for osteopontin. Semiquantitative RT-PCR was performed
      for the osteoblast bone markers [alkaline phosphatase, osteopontin, and
      osteoblast lineage-specific transcription factor (Cbfa-1)]. There was an increase
      in cholesterol, hsCRP, PCNA, RAM 11, and osteopontin and osteoblast gene markers
      (alkaline phosphatase, osteopontin, and Cbfa-1) in the cholesterol-fed rabbits
      compared with control rabbits. All markers except hsCRP were reduced by
      atorvastatin. CONCLUSIONS: These findings of increased macrophages, PCNA levels,
      and bone matrix proteins in the aortic valve during experimental
      hypercholesterolemia provide evidence of a proliferative atherosclerosis-like
      process in the aortic valve associated with the transformation to an osteoblast
      like phenotype that is inhibited by atorvastatin.

PMID- 12045175
TI  - Dynamic nature of atrial fibrillation substrate during development and reversal
      of heart failure in dogs.
AB  - BACKGROUND: Clinical atrial fibrillation (AF) often results from pathologies that
      cause atrial structural remodeling. The reversibility of arrhythmogenic
      structural remodeling on removal of the underlying stimulus has not been studied
      systematically. METHODS AND RESULTS: Chronically instrumented dogs were subjected
      to 4 to 6 weeks of ventricular tachypacing (VTP; 220 to 240 bpm) to induce
      congestive heart failure (CHF), followed by a 5-week recovery period leading to
      hemodynamic normalization at 5-week recovery (Wk5(rec)). The duration of burst
      pacing-induced AF under ketamine/diazepam/isoflurane anesthesia increased
      progressively during VTP and recovered toward baseline during the recovery
      period, paralleling changes in atrial dimensions. However, even at full recovery,
      sustained AF could still be induced under relatively vagotonic
      morphine/chloralose anesthesia. Wk5(rec) dogs showed no recovery of CHF-induced
      atrial fibrosis (3.1+/-0.3% for controls versus 10.7+/-1.0% for CHF and 12.0+/
      0.8% for Wk5(rec) dogs) or local conduction abnormalities (conduction
      heterogeneity index 1.8+/-0.1 in controls versus 2.3+/-0.1 in CHF and 2.2+/-0.2
      in Wk5(rec) dogs). One week of atrial tachypacing failed to affect the right
      atrial effective refractory period significantly in CHF dogs but caused highly
      significant effective refractory period reductions and atrial vulnerability
      increases in Wk5(rec) dogs. CONCLUSIONS: Reversal of CHF is followed by
      normalized atrial function and decreased duration of AF; however, fibrosis and
      conduction abnormalities are not reversible, and a substrate that can support
      prolonged AF remains. Early intervention to prevent fixed structural
      abnormalities may be important in patients with conditions that predispose to the
      arrhythmia.

PMID- 12045177
TI  - Expansive arterial remodeling is associated with increased neointimal macrophage
      foam cell content: the murine model of macrophage-rich carotid artery lesions.
AB  - BACKGROUND: Recent observations associate plaque instability with expansive
      arterial remodeling, suggesting a common driving mechanism. METHODS AND RESULTS:
      To demonstrate that macrophages, a characteristic of vulnerable plaques, also
      assist in expansive remodeling, we compared carotid artery remodeling due to
      formation of experimental macrophage-rich and macrophage-poor lesions in the flow
      cessation model in hypercholesterolemic apolipoprotein E knockout (ApoE KO) and
      wild type (WT) mice. After ligation, macrophages started to rapidly accumulate in
      ApoE KO but not in WT carotid artery lesions. Macrophage-rich ApoE KO intimal
      lesions grew fast, typically occluding within 14 days, despite a tripling of the
      vessel area. Outward remodeling of macrophage-rich ApoE KO arteries positively
      correlated with macrophage area (r2=0.600, P<0.001). To investigate potential
      mechanisms of macrophage-enabled expansive remodeling, we compared levels of
      matrix metalloproteinases in homogenates of macrophage-rich and macrophage-poor
      carotid arteries. Gelatinolytic activity of macrophage-rich lesions increased
      faster and reached maximal levels several fold higher than in the macrophage-poor
      WT lesions. CONCLUSIONS: Our results suggest that macrophages facilitate
      expansive arterial remodeling through increased matrix degradation by matrix
      metalloproteinases. This initially favorable remodeling action may eventually
      increase the vulnerability of macrophage-rich atherosclerotic plaques.

PMID- 12045176
TI  - Electrophysiology and arrhythmogenic activity of single cardiomyocytes from
      canine superior vena cava.
AB  - BACKGROUND: The superior vena cava (SVC) has been proved to be a focal point in
      the initiation of paroxysmal atrial fibrillation. The autonomic nervous system
      plays an important role in the genesis of atrial fibrillation. However, the
      arrhythmogenic potentials of SVC and its responses to autonomic agents are not
      clear. The purpose of this study was to isolate single SVC cardiomyocytes and to
      investigate their electrophysiological characteristics, as well as the direct
      effects of autonomic agents. METHODS AND RESULTS: Canine SVC cardiomyocytes were
      isolated by perfusion with digestive enzymes. The action potentials and ionic
      currents were investigated in single SVC cardiomyocytes using the whole-cell
      clamp technique. Dissociation of the SVC yielded rod-shaped single cardiomyocytes
      with (n=74, 51%) or without (n=71, 49%) pacemaker activities. There were similar
      densities of inward Ca2+, delayed rectifier K+, transient inward, inward
      rectifier K+, and pacemaker currents between SVC cardiomyocytes with and without
      pacemaker activity. SVC cardiomyocytes with pacemaker activity have, however,
      greater transient outward currents than those without pacemaker activity. In SVC
      cardiomyocytes, acetylcholine (5.5 micromol/L) abolished the spontaneous
      activities, but isoproterenol (10 nmol/L), atropine (10 micromol/L), and
      phenylephrine (10 micromol/L) accelerated the spontaneous activity and induced
      the occurrences of early or delayed afterdepolarizations. CONCLUSIONS: These
      findings suggest that SVC cardiomyocytes have distinct action potentials and
      ionic current profiles that may be responsible for the arrhythmogenic activity of
      the SVC.

PMID- 12045178
TI  - Images in cardiovascular medicine. Assessment of double chamber right ventricle
      by magnetic resonance imaging.

PMID- 12045179
TI  - Images in cardiovascular medicine. Angiographic evidence of coronary-subclavian
      steal syndrome.

PMID- 12045180
TI  - Inflammation-sensitive proteins: another ingredient in stroke?

PMID- 12045181
TI  - c-erbB-3: a nuclear protein in mammary epithelial cells.
AB  - c-erbB receptors are usually located in cell membranes and are activated by
      extracellular binding of EGF-like growth factors. Unexpectedly, using
      immunofluorescence we found high levels of c-erbB-3 within the nuclei of MTSV1-7
      immortalized nonmalignant human mammary epithelial cells. Nuclear localization
      was mediated by the COOH terminus of c-erbB-3, and a nuclear localization signal
      was identified by site-directed mutagenesis and by transfer of the signal to
      chicken pyruvate kinase. A nuclear export inhibitor caused accumulation of c-erbB
      3 in the nuclei of other mammary epithelial cell lines as demonstrated by
      immunofluorescence and biochemical cell fractionation, suggesting that c-erbB-3
      shuttles between nuclear and nonnuclear compartments in these cells. Growth of
      MTSV1-7 on permeable filters induced epithelial polarity and concentration of c
      erbB-3 within the nucleoli. However, the c-erbB-3 ligand heregulin beta1 shifted
      c-erbB-3 from the nucleolus into the nucleoplasm and then into the cytoplasm. The
      subcellular localization of c-erbB-3 obviously depends on exogenous stimuli and
      on the stage of epithelial polarity and challenges the specific function of c
      erbB-3 as a transmembrane receptor protein arguing for additional, as yet
      unidentified, roles of c-erbB-3 within the nucle(ol)us of mammary epithelial
      cells.

PMID- 12045182
TI  - Genetic analysis of the role of G protein-coupled receptor signaling in
      electrotaxis.
AB  - Cells display chemotaxis and electrotaxis by migrating directionally in gradients
      of specific chemicals or electrical potential. Chemotaxis in Dictyostelium
      discoideum is mediated by G protein-coupled receptors. The unique Gbeta is
      essential for all chemotactic responses, although different chemoattractants use
      different receptors and Galpha subunits. Dictyostelium amoebae show striking
      electrotaxis in an applied direct current electric field. Perhaps electrotaxis
      and chemotaxis share similar signaling mechanisms? Null mutation of Gbeta and
      cAMP receptor 1 and Galpha2 did not abolish electrotaxis, although Gbeta-null
      mutations showed suppressed electrotaxis. By contrast, G protein signaling plays
      an essential role in chemotaxis. G protein-coupled receptor signaling was
      monitored with PHcrac-green fluorescent protein, which translocates to inositol
      phospholipids at the leading edge of cells during chemotaxis. There was no
      intracellular gradient of this protein during electrotaxis. However, F-actin was
      polymerized at the leading edge of cells during electrotaxis. We conclude that
      reception and transduction of the electrotaxis signal are largely independent of
      G protein-coupled receptor signaling and that the pathways driving chemotaxis and
      electrotaxis intersect downstream of heterotrimeric G proteins to invoke
      cytoskeletal elements.

PMID- 12045184
TI  - Ecdysone-induced expression of the caspase DRONC during hormone-dependent
      programmed cell death in Drosophila is regulated by Broad-Complex.
AB  - The steroid hormone ecdysone regulates both cell differentiation and cell death
      during insect metamorphosis, by hierarchical transcriptional regulation of a
      number of genes, including the Broad-Complex (BR-C), the zinc finger family of
      transcription factors. These genes in turn regulate the transcription of a number
      of downstream genes. DRONC, a key apical caspase in Drosophila, is the only known
      caspase that is transcriptionally regulated by ecdysone during development. We
      demonstrate that dronc gene expression is ablated or reduced in BR-C mutant
      flies. Using RNA interference in an ecdysone-responsive Drosophila cell line, we
      show that DRONC is essential for ecdysone-mediated cell death, and that dronc
      upregulation in these cells is controlled by BR-C. Finally, we show that the
      dronc promoter has BR-C interaction sites, and that it can be transactivated by a
      specific isoform of BR-C. These results indicate that BR-C plays a key role in
      ecdysone-mediated caspase regulation.

PMID- 12045183
TI  - Ypt32 recruits the Sec4p guanine nucleotide exchange factor, Sec2p, to secretory
      vesicles; evidence for a Rab cascade in yeast.
AB  - SEC2 is an essential gene required for polarized growth of the yeast
      Saccharomyces cerevisiae. It encodes a protein of 759 amino acids that functions
      as a guanine nucleotide exchange factor for the small GTPase Sec4p, a regulator
      of Golgi to plasma membrane transport. Activation of Sec4p by Sec2p is needed for
      polarized transport of vesicles to exocytic sites. Temperature-sensitive (ts)
      mutations in sec2 and sec4 result in a tight block in secretion and the
      accumulation of secretory vesicles randomly distributed in the cell. The proper
      localization of Sec2p to secretory vesicles is essential for its function and is
      largely independent of Sec4p. Although the ts mutation sec2-78 does not affect
      nucleotide exchange activity, the protein is mislocalized. Here we present
      evidence that Ypt31/32p, members of Rab family of GTPases, regulate Sec2p
      function. First, YPT31/YPT32 suppress the sec2-78 mutation. Second,
      overexpression of Ypt31/32p restores localization of Sec2-78p. Third, Ypt32p and
      Sec2p interact biochemically, but Sec2p has no exchange activity on Ypt32p. We
      propose that Ypt32p and Sec4p act as part of a signaling cascade in which Ypt32p
      recruits Sec2p to secretory vesicles; once on the vesicle, Sec2p activates Sec4p,
      enabling the polarized transport of vesicles to the plasma membrane.

PMID- 12045185
TI  - Characterization of Tbc2, a nucleus-encoded factor specifically required for
      translation of the chloroplast psbC mRNA in Chlamydomonas reinhardtii.
AB  - Genetic analysis has revealed that the three nucleus-encoded factors Tbc1, Tbc2,
      and Tbc3 are involved in the translation of the chloroplast psbC mRNA of the
      eukaryotic green alga Chlamydomonas reinhardtii. In this study we report the
      isolation and phenotypic characterization of two new tbc2 mutant alleles and
      their use for cloning and characterizing the Tbc2 gene by genomic
      complementation. TBC2 encodes a protein of 1,115 residues containing nine copies
      of a novel degenerate 38-40 amino acid repeat with a quasiconserved PPPEW motif
      near its COOH-terminal end. The middle part of the Tbc2 protein displays partial
      amino acid sequence identity with Crp1, a protein from Zea mays that is
      implicated in the processing and translation of the chloroplast petA and petD
      RNAs. The Tbc2 protein is enriched in chloroplast stromal subfractions and is
      associated with a 400-kD protein complex that appears to play a role in the
      translation of specifically the psbC mRNA.

PMID- 12045186
TI  - Retinoic acid stimulates annexin-mediated growth plate chondrocyte
      mineralization.
AB  - Biomineralization is a highly regulated process that plays a major role during
      the development of skeletal tissues. Despite its obvious importance, little is
      known about its regulation. Previously, it has been demonstrated that retinoic
      acid (RA) stimulates terminal differentiation and mineralization of growth plate
      chondrocytes (Iwamoto, M., I.M. Shapiro, K. Yagumi, A.L. Boskey, P.S. Leboy, S.L.
      Adams, and M. Pacifici. 1993. Exp. Cell Res. 207:413-420). In this study, we
      provide evidence that RA treatment of growth plate chondrocytes caused a series
      of events eventually leading to mineralization of these cultures: increase in
      cytosolic calcium concentration, followed by up-regulation of annexin II, V, and
      VI gene expression, and release of annexin II-, V-, VI- and alkaline phosphatase
      containing matrix vesicles. Cotreatment of growth plate chondrocytes with RA and
      BAPTA-AM, a cell permeable Ca2+ chelator, inhibited the up-regulation of annexin
      gene expression and mineralization of these cultures. Interestingly, only matrix
      vesicles isolated from RA-treated cells that contained annexins, were able to
      take up Ca2+ and mineralize, whereas vesicles isolated from untreated or RA/BAPTA
      treated cells, that contained no or only little annexins were not able to take up
      Ca2+ and mineralize. Cotreatment of chondrocytes with RA and EDTA revealed that
      increases in the cytosolic calcium concentration were due to influx of
      extracellular calcium. Interestingly, the novel 1,4-benzothiazepine derivative K
      201, a specific annexin Ca2+ channel blocker, or antibodies specific for annexin
      II, V, or VI inhibited the increases in cytosolic calcium concentration in RA
      treated chondrocytes. These findings indicate that annexins II, V, and VI form
      Ca2+ channels in the plasma membrane of terminally differentiated growth plate
      chondrocytes and mediate Ca2+ influx into these cells. The resulting increased
      cytosolic calcium concentration leads to a further up-regulation of annexin II,
      V, and VI gene expression, the release of annexin II-, V-, VI- and alkaline
      phosphatase-containing matrix vesicles, and the initiation of mineralization by
      these vesicles.

PMID- 12045188
TI  - Rotation of the c subunit oligomer in EF(0)EF(1) mutant cD61N.
AB  - ATP synthases (F(0)F(1)-ATPases) mechanically couple ion flow through the
      membrane-intrinsic portion, F(0), to ATP synthesis within the peripheral portion,
      F(1). The coupling most probably occurs through the rotation of a central rotor
      (subunits c(10)epsilon gamma) relative to the stator (subunits ab(2)delta(alpha
      beta)(3)). The translocation of protons is conceived to involve the rotation of
      the ring of c subunits (the c oligomer) containing the essential acidic residue
      cD61 against subunits ab(2). In line with this notion, the mutants cD61N and
      cD61G have been previously reported to lack proton translocation. However, it has
      been surprising that the membrane-bound mutated holoenzyme hydrolyzed ATP but
      without translocating protons. Using detergent-solubilized and immobilized
      EF(0)F(1) and by application of the microvideographic assay for rotation, we
      found that the c oligomer, which carried a fluorescent actin filament, rotates in
      the presence of ATP in the mutant cD61N just as in the wild type enzyme. This
      observation excluded slippage among subunit gamma, the central rotary shaft, and
      the c oligomer and suggested free rotation without proton pumping between the
      oligomer and subunit a in the membrane-bound enzyme.

PMID- 12045187
TI  - Nuclear and cytoplasmic shuttling of TRADD induces apoptosis via different
      mechanisms.
AB  - The adapter protein tumor necrosis factor receptor (TNFR)1-associated death
      domain (TRADD) plays an essential role in recruiting signaling molecules to the
      TNFRI receptor complex at the cell membrane. Here we show that TRADD contains a
      nuclear export and import sequence that allow shuttling between the nucleus and
      the cytoplasm. In the absence of export, TRADD is found within nuclear structures
      that are associated with promyelocytic leukemia protein (PML) nuclear bodies. In
      these structures, the TRADD death domain (TRADD-DD) can activate an apoptosis
      pathway that is mechanistically distinct from its action at the membrane-bound
      TNFR1 complex. Apoptosis by nuclear TRADD-DD is promyelocytic leukemia protein
      dependent, involves p53, and is inhibited by Bcl-xL but not by caspase inhibitors
      or dominant negative FADD (FADD-DN). Conversely, apoptosis induced by TRADD in
      the cytoplasm is resistant to Bcl-xL, but sensitive to caspase inhibitors and
      FADD-DN. These data indicate that nucleocytoplasmic shuttling of TRADD leads to
      the activation of distinct apoptosis mechanisms that connect the death receptor
      apparatus to nuclear events.

PMID- 12045189
TI  - Engagement of CD43 enhances human immunodeficiency virus type 1 transcriptional
      activity and virus production that is induced upon TCR/CD3 stimulation.
AB  - Human immunodeficiency virus type 1 (HIV-1) transcriptional activity is regulated
      by several cytokines and T cell activators. CD43 (sialophorin) is a
      sialoglycoprotein expressed on the surface of a wide variety of blood cells
      including T lymphocytes. Several studies have shown that CD43 ligation induces
      proliferation and activation of human T lymphocytes. We were thus interested in
      defining whether CD43-mediated signaling events can modulate the life cycle of
      HIV-1. We demonstrate here that CD43 cross-linking potentiates HIV-1 promoter
      driven activity and virus production that is seen following the engagement of the
      T-cell receptor (TCR).CD3 complex. This effect is independent of the CD28 co
      stimulatory molecule and is mediated by both NF-kappaB and NFAT transcription
      factors. A number of signal transducers known to be involved in the TCR/CD3
      dependent signal transduction pathway, including p56(lck), p36(lat), and SLP-76,
      as well as capacitative entry of calcium, are crucial for the noticed CD43 co
      stimulatory effect. Calcium mobilization studies indicate that a synergy is
      occurring between CD43- and TCR/CD3-mediated signaling events leading to an
      augmented calcium release. These data suggest that CD43 can be seen as a co
      stimulatory cell surface constituent that can modulate HIV-1 expression in T
      lymphocytes.

PMID- 12045190
TI  - Identification of domains directing specificity of coupling to G-proteins for the
      melanocortin MC3 and MC4 receptors.
AB  - The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that
      are involved in regulating energy homeostasis. Using a luciferase reporter gene
      under the transcriptional control of a cAMP- responsive element (CRE), the
      coupling efficiency of the MC4R and MC3R to G-proteins was previously shown to be
      different. MC4R exhibited only 30-50% of the maximum activity induced by MC3R. To
      assess the role of the different MC3R and MC4R domains in G-protein coupling,
      several chimeric MC3R/MC4R receptors were constructed. The relative luciferase
      activities, which were assessed after transfecting the chimeric receptors into
      HEK 293T cells, showed that the i3 (3rd intracellular) loop domain has an
      essential role in the differential signaling of MC3R and MC4R. To reveal which
      amino acid residue was involved in the MC4R-specific signaling in the i3 loop, a
      series of mutant MC4Rs was constructed. Reporter gene analysis showed that single
      mutations of Arg(220) to Ala and Thr(232) to either Val or Ala increased the
      relative luciferase activities, which suggests that these specific amino acids,
      Arg(220) and Thr(232), in the i3 loop of MC4R play crucial roles in G-protein
      coupling and the subtype-specific signaling pathways. An examination of the
      inositol phosphate (IP) levels in the cells transfected with either MC3R or MC4R
      after being exposed to the melanocortin peptides revealed significant stimulation
      of IP production by MC3R but no detectable increase in IP production was observed
      by MC4R. Furthermore, none of the MC4R mutants displayed melanocortin peptide
      stimulated IP production. Overall, this study demonstrated that MC3R and MC4R
      have distinct signaling in either the cAMP- or the inositol phospholipid-mediated
      pathway with different conformational requirements.

PMID- 12045191
TI  - Alternative splicing of the primary transcript generates heterogeneity within the
      products of the gene for Bombyx mori chitinase.
AB  - The gene of chitinase in the silkworm, Bombyx mori, generates four mRNA products
      by alternative splicing. Nucleotide sequences of the entire gene for chitinase
      and respective cDNAs demonstrate that the pre-mRNA undergoes alternative splicing
      at both the 5' and 3' regions. At the 5' region, the pre-mRNA experienced
      differential splicing through two alternative 5'-intron consensus splicing sites.
      These products differ in the last amino acid of the signal peptide and the first
      amino acid of the mature N-terminal sequences: one with Cys(20)-Ala(21) and the
      other with Ser(20)-Asp(21). The product with Cys(20)-Ala(21) residues is one
      amino acid larger than the other with Ser(20)-Asp(21). At the 3' region the pre
      mRNA of the chitinase gene undergoes alternative splicing in three different
      fashions. It is spliced either through retaining or excluding the upstream 121-bp
      direct repeat found at the 3' region of the coding sequences or through retaining
      or excluding of an insertion of 9 bp in a combinatorial manner. Retention or
      exclusion of the upstream 121-bp direct repeat results in a protein with a
      deduced amino acid sequence similar in size to the one retaining both direct
      repeats. However, exclusion of the insert of the 9 bp from the mRNA results in a
      protein with 22 extra amino acids. All of the mRNA products appear to be
      generated from a single gene as demonstrated by testing the 3' region of the
      genomic DNA and variant chitinase mRNA products. B. mori chitinase expression in
      the fifth instar larvae epidermal tissues appears to be developmentally
      regulated, but the phenomenon of alternative splicing of the pre-mRNA is not
      stage-dependent. Furthermore, the four mRNA products showed chitinase activity
      when expressed in Escherichia coli, which demonstrates the role of the
      alternative splicing process in generating multiple isoforms of the silkworm's
      chitinase.

PMID- 12045192
TI  - The large subunit of replication factor C interacts with the histone deacetylase,
      HDAC1.
AB  - Replication factor C (RFC) is a pentameric complex of five distinct subunits that
      functions as a clamp loader, facilitating the loading of proliferating cell
      nuclear antigen (PCNA) onto DNA during replication and repair. More recently the
      large subunit of RFC, RFC (p140), has been found to interact with the
      retinoblastoma (Rb) tumor suppressor and the CCAAT/enhancer-binding protein alpha
      (C/EBP alpha) transcription factor. We now report that RFC (p140) associates with
      histone deacetylase activity and interacts with histone deacetylase 1 (HDAC1).
      This complex is functional and when targeted to promoters as a Gal4 fusion, RFC
      (p140) is a strong, deacetylase-dependent repressor of transcription. Further
      analysis revealed that RFC (p140) contains two distinct transcriptional
      repression domains. Moreover, both of these domains interact separately with
      HDAC1.

PMID- 12045193
TI  - The crystal structure of metal-free human EF-hand protein S100A3 at 1.7-A
      resolution.
AB  - S100A3 is a unique member of the EF-hand superfamily of Ca(2+)-binding proteins.
      It binds Ca(2+) with poor affinity (K(d) = 4-35 mm) but Zn(2+) with exceptionally
      high affinity (K(d) = 4 nm). This high affinity for Zn(2+) is attributed to the
      unusual high Cys content of S100A3. The protein is highly expressed in fast
      proliferating hair root cells and astrocytoma pointing toward a function in cell
      cycle control. We determined the crystal structure of the protein at 1.7 A. The
      high resolution structure revealed a large distortion of the C-terminal canonical
      EF-hand, which most likely abolishes Ca(2+) binding. The crystal structure of
      S100A3 allows the prediction of one putative Zn(2+) binding site in the C
      terminus of each subunit of S100A3 involving Cys and His residues in the
      coordination of the metal ion. Zn(2+) binding induces a large conformational
      change in S100A3 perturbing the hydrophobic interface between two S100A3
      subunits, as shown by size exclusion chromatography and CD spectroscopy.

PMID- 12045194
TI  - Soluble phosphatidylserine triggers assembly in solution of a prothrombin
      activating complex in the absence of a membrane surface.
AB  - Factor X(a) (FX(a)) binding to factor V(a) (FV(a)) on platelet-derived membranes
      containing surface-exposed phosphatidylserine (PS) forms the "prothrombinase
      complex" that is essential for efficient thrombin generation during blood
      coagulation. There are two naturally occurring isoforms of FV(a), FV(a1) and
      FV(a2). These two isoforms differ by a 3-kDa polysaccharide chain (at Asn(2181)
      in human FV(a1) (Kim, S. W., Ortel, T. L., Quinn-Allen, M. A., Yoo, L., Worfolk,
      L., Zhai, X., Lentz, B. R., and Kane, W. H. (1999) Biochemistry 38, 11448-11454))
      and have different coagulant activities. We examined the interaction of the two
      bovine isoforms with active site-labeled FX(a), finding no significant
      difference. A soluble form of PS (C6PS) bound to FV(a1) and FV(a2) with
      comparable affinities (K(d) = 11-12 microm) and changes in FV(a) intrinsic
      fluorescence. At concentrations well below its critical micelle concentration,
      C6PS binding to bovine FV(a2) enhanced its affinity for FX(a) in solution by
      nearly 3 orders of magnitude (K(d)(eff) = 40-2 nm over a C6PS range of 30-400
      microm) but had no effect on the affinity of FV(a1) for FX(a) (K(d) = 1 microm).
      This results in a soluble complex between FX(a) and FV(a2), whose expected
      molecular weight was confirmed by calibrated native gel electrophoresis. This
      complex behaved as a normal Michaelis-Menten enzyme in its ability to produce
      thrombin from meizothrombin (apparent k(cat)/K(m) congruent with 10(9) m(-1) s(
      1)). The ability of soluble PS to trigger formation of a soluble prothrombinase
      complex suggests that exposure of PS molecules during platelet activation is
      likely the key event responsible for the assembly of an active membrane-bound
      complex.

PMID- 12045195
TI  - Somatostatin, acting at receptor subtype 1, inhibits Rho activity, the assembly
      of actin stress fibers, and cell migration.
AB  - Somatostatin regulates multiple biological functions by acting through a family
      of five G protein-coupled receptors, somatostatin receptors (SSTRs) 1-5. Although
      all five receptor subtypes inhibit adenylate cyclase activity and decrease
      intracellular cAMP levels, specific receptor subtypes also couple to additional
      signaling pathways. In CCL39 fibroblasts expressing either human SSTR1 or SSTR2,
      we demonstrate that activation of SSTR1 (but not SSTR2) attenuated both thrombin-
      and integrin-stimulated Rho-GTP complex formation. The reduction in Rho-GTP
      formation in the presence of somatostatin was associated with decreased
      translocation of Rho and LIM kinase to the plasma membrane and fewer focal
      contacts. Activation of Rho resulted in the formation of intracellular actin
      stress fibers and cell migration. In CCL39-R1 cells, somatostatin treatment
      prevented actin stress fiber assembly and attenuated thrombin-stimulated cell
      migration through Transwell membranes to basal levels. To show that native SSTR1
      shares the ability to inhibit Rho activation, we demonstrated that somatostatin
      treatment of human umbilical vein endothelial cells attenuated thrombin
      stimulated Rho-GTP accumulation. These data show for the first time that a G
      protein-coupled receptor, SSTR1, inhibits the activation of Rho, the assembly of
      focal adhesions and actin stress fibers, and cell migration.

PMID- 12045196
TI  - Redundant mitochondrial targeting signals in yeast adenylate kinase.
AB  - Yeast adenylate kinase (Aky2p, Adk1p) occurs simultaneously in cytoplasm and
      mitochondrial intermembrane space. It has no cleavable mitochondrial targeting
      sequence, and the signal for mitochondrial import and submitochondrial sorting is
      largely unknown. The extreme N terminus of Aky2p is able to direct cytoplasmic
      passengers to mitochondria. However, an Aky2 mutant lacking this sequence is
      imported with about the same efficiency as the wild type. To identify possible
      import-relevant information in the interior, parts of Aky2p were exchanged by
      homologous in vitro recombination for the respective segments of the purely
      cytoplasmic isozyme, Ura6p. Import studies revealed an internal region of about
      40 amino acids, which was sufficient to direct the chimera to mitochondria but
      not for correct submitochondrial sorting. The respective Ura6p hybrid was
      arrested in the mitochondrial membrane at a position where it was inaccessible to
      protease but was released by alkaline extraction, suggesting that it had entered
      an import channel and passed the initial steps of recognition and uptake. Site
      specific mutations within the presumptive address-specifying segment identified
      the amphipathic helix 5. A Ura6 mutant protein in which helix 5 had been replaced
      with the respective sequence from Aky2p was imported, and this address sequence
      cooperates with the N terminus in the respective double mutant in a synergistic
      fashion.

PMID- 12045197
TI  - A modulatory role for the troponin T tail domain in thin filament regulation.
AB  - In striated muscle the force generating acto-myosin interaction is sterically
      regulated by the thin filament proteins tropomyosin and troponin (Tn), with the
      position of tropomyosin modulated by calcium binding to troponin. Troponin itself
      consists of three subunits, TnI, TnC, and TnT, widely characterized as being
      responsible for separate aspects of the regulatory process. TnI, the inhibitory
      unit is released from actin upon calcium binding to TnC, while TnT performs a
      structural role forming a globular head region with the regulatory TnI- TnC
      complex with a tail anchoring it within the thin filament. We have examined the
      properties of TnT and the TnT(1) tail fragment (residues 1-158) upon
      reconstituted actin-tropomyosin filaments. Their regulatory effects have been
      characterized in both myosin S1 ATPase and S1 kinetic and equilibrium binding
      experiments. We show that both inhibit the actin-tropomyosin-activated S1 ATPase
      with TnT(1) producing a greater inhibitory effect. The S1 binding data show that
      this inhibition is not caused by the formation of the blocked B-state but by
      significant stabilization of the closed C-state with a 10-fold reduction in the C
      to M-state equilibrium, K(T), for TnT(1). This suggests TnT has a modulatory as
      well as structural role, providing an explanation for its large number of
      alternative isoforms.

PMID- 12045198
TI  - Long CTG.CAG repeat sequences markedly stimulate intramolecular recombination.
AB  - Previous studies have shown that homologous recombination is a powerful mechanism
      for generation of massive instabilities of the myotonic dystrophy CTG.CAG
      sequences. However, the frequency of recombination between the CTG.CAG tracts has
      not been studied. Here we performed a systematic study on the frequency of
      recombination between these sequences using a genetic assay based on an
      intramolecular plasmid system in Escherichia coli. The rate of intramolecular
      recombination between long CTG.CAG tracts oriented as direct repeats was
      extraordinarily high; recombinants were found with a frequency exceeding 12%.
      Recombination occurred in both RecA(+) and RecA(-) cells but was approximately 2
      11 times higher in the recombination proficient strain. Long CTG.CAG tracts
      recombined approximately 10 times more efficiently than non-repeating control
      sequences of similar length. The recombination frequency was 60-fold higher for a
      pair of (CTG.CAG)(165) tracts compared with a pair of (CTG.CAG)(17) sequences.
      The CTG.CAG sequences in orientation II (CTG repeats present on a lagging strand
      template) recombine approximately 2-4 times more efficiently than tracts of
      identical length in the opposite orientation relative to the origin of
      replication. This orientation effect implies the involvement of DNA replication
      in the intramolecular recombination between CTG.CAG sequences. Thus, long CTG.CAG
      tracts are hot spots for genetic recombination.

PMID- 12045199
TI  - Photoinduced electron transfer between the Rieske iron-sulfur protein and
      cytochrome c(1) in the Rhodobacter sphaeroides cytochrome bc(1) complex. Effects
      of pH, temperature, and driving force.
AB  - Electron transfer from the Rieske iron-sulfur protein to cytochrome c(1) (cyt
      c(1)) in the Rhodobacter sphaeroides cytochrome bc(1) complex was studied using a
      ruthenium dimer complex, Ru(2)D. Laser flash photolysis of a solution containing
      reduced cyt bc(1), Ru(2)D, and a sacrificial electron acceptor results in
      oxidation of cyt c(1) within 1 micros, followed by electron transfer from the
      iron-sulfur center (2Fe-2S) to cyt c(1) with a rate constant of 80,000 s(-1).
      Experiments were carried out to evaluate whether the reaction was rate-limited by
      true electron transfer, proton gating, or conformational gating. The temperature
      dependence of the reaction yielded an enthalpy of activation of +17.6 kJ/mol,
      which is consistent with either rate-limiting conformational gating or electron
      transfer. The rate constant was nearly independent of pH over the range pH 7 to
      9.5 where the redox potential of 2Fe-2S decreases significantly due to
      deprotonation of His-161. The rate constant was also not greatly affected by the
      Rieske iron-sulfur protein mutations Y156W, S154A, or S154A/Y156F, which decrease
      the redox potential of 2Fe-2S by 62, 109, and 159 mV, respectively. It is
      concluded that the electron transfer reaction from 2Fe-2S to cyt c(1) is
      controlled by conformational gating.

PMID- 12045200
TI  - Tuberin regulates p70 S6 kinase activation and ribosomal protein S6
      phosphorylation. A role for the TSC2 tumor suppressor gene in pulmonary
      lymphangioleiomyomatosis (LAM).
AB  - Although the cellular functions of TSC2 and its protein product, tuberin, are not
      known, somatic mutations in the TSC2 tumor suppressor gene are associated with
      tumor development in lymphangioleiomyomatosis (LAM). We found that ribosomal
      protein S6 (S6), which exerts translational control of protein synthesis and is
      required for cell growth, is hyperphosphorylated in the smooth muscle-like cell
      lesions of LAM patients compared with smooth muscle cells from normal human blood
      vessels and trachea. Smooth muscle (SM) cells derived from these lesions (LAMD
      SM) also exhibited S6 hyperphosphorylation, constitutive activation of p70 S6
      kinase (p70S6K), and increased basal DNA synthesis. In parallel, TSC2-/- smooth
      muscle cells (ELT3) and TSC2-/- epithelial cells (ERC15) also exhibited
      hyperphosphorylation of S6, constitutive activation of p70S6K, and increased
      basal DNA synthesis. Re-introduction of wild type tuberin into LAMD-SM, ELT3, and
      ERC15 cells abolished phosphorylation of S6 and significantly inhibited p70S6K
      activity and DNA synthesis. Rapamycin, an immunosuppressant, inhibited
      hyperphosphorylation of S6, p70S6K activation, and DNA synthesis in LAMD-SM
      cells. Interestingly, the basal levels of phosphatidylinositol 3-kinase,
      Akt/protein kinase B, and p42/p44 MAPK activation were unchanged in LAMD-SM and
      ELT3 cells relative to levels in normal human tracheal and vascular SM. These
      data demonstrate that tuberin negatively regulates the activity of S6 and p70S6K
      specifically, and suggest a potential mechanism for abnormal cell growth in LAM.

PMID- 12045201
TI  - Cholesterol and bile acids regulate xenosensor signaling in drug-mediated
      induction of cytochromes P450.
AB  - Cytochromes P450 (CYP) constitute the major enzymatic system for metabolism of
      xenobiotics. Here we demonstrate that transcriptional activation of CYPs by the
      drug-sensing nuclear receptors pregnane X receptor, constitutive androstane
      receptor, and the chicken xenobiotic receptor (CXR) can be modulated by
      endogenous cholesterol and bile acids. Bile acids induce the chicken drug
      activated CYP2H1 via CXR, whereas the hydroxylated metabolites of bile acids and
      oxysterols inhibit drug induction. The cholesterol-sensing liver X receptor
      competes with CXR, pregnane X receptor, or constitutive androstane receptor for
      regulation of drug-responsive enhancers from chicken CYP2H1, human CYP3A4, or
      human CYP2B6, respectively. Thus, not only cholesterol 7 alpha-hydroxylase
      (CYP7A1), but also drug-inducible CYPs, are diametrically affected by these
      receptors. Our findings reveal new insights into the increasingly complex network
      of nuclear receptors regulating lipid homeostasis and drug metabolism.

PMID- 12045202
TI  - Strong aggregation and increased toxicity of polyleucine over polyglutamine
      stretches in mammalian cells.
AB  - Expansion of a Glutamine (Gln) repeat above a specific critical size in certain
      proteins gives rise to aggregation-prone proteins that cause neurodegenerative
      disorders, such as Huntington's disease. However, proteins with long hydrophilic
      polyglutamine repeats are more frequently found in nature than proteins with long
      homogeneous repeats of other amino acids, such as hydrophobic (Ala)(n) and
      (Leu)(n). To explore this finding, the effects of expression in mammalian cells
      of polyglutamine and polyleucine encoded by mixed DNA repeats were compared. It
      was found that polyleucine is significantly more toxic than polyglutamine. In
      addition, we show that polyleucine stretches display a high propensity for
      aggregation utilizing two complementary biochemical assays and that polyleucine
      stretches can also be detected by the monoclonal antibody 1C2, which specifically
      recognizes expanded pathogenic and aggregation-prone glutamine repeats. Together,
      these results suggest that polyglutamine stretches are in fact relatively well
      tolerated and that nature may select more strongly against DNA stretches that
      encode long hydrophobic homopolymeric amino acid stretches, such as polyleucine -
      possibly owing to their strong propensity for aggregation. In keeping with this
      notion, an increasing number of diseases are found to be associated with
      expansion of stretches of hydrophobic amino acids, including oculopharyngeal
      muscular dystrophy (OPMD), which is associated with expansion of a hydrophobic
      polyalanine stretch.

PMID- 12045203
TI  - Growth arrest by the LKB1 tumor suppressor: induction of p21(WAF1/CIP1).
AB  - Germline mutations of the LKB1 tumor suppressor gene lead to Peutz-Jeghers
      syndrome (PJS), with a predisposition to cancer. LKB1 encodes for a nuclear and
      cytoplasmic serine/threonine kinase, which is inactivated by mutations observed
      in PJS patients. Restoring LKB1 activity into cancer cell lines defective for its
      expression results in a G(1) cell cycle arrest. Here we have investigated
      molecular mechanisms leading to this arrest. Reintroduced active LKB1 was
      cytoplasmic and nuclear, whereas most kinase-defective PJS mutants of LKB1
      localized predominantly to the nucleus. Moreover, when LKB1 was forced to remain
      cytoplasmic through disruption of the nuclear localization signal, it retained
      full growth suppression activity in a kinase-dependent manner. LKB1-mediated G(1)
      arrest was found to be bypassed by co-expression of the G(1) cyclins cyclin D1
      and cyclin E. In addition, the protein levels of the CDK inhibitor p21(WAF1/CIP1)
      and p21 promoter activity were specifically upregulated in LKB1-transfected
      cells. Both the growth arrest and the induction of the p21 promoter were found to
      be p53-dependent. These results suggest that growth suppression by LKB1 is
      mediated through signaling of cytoplasmic LKB1 to induce p21 through a p53
      dependent mechanism.

PMID- 12045204
TI  - Polyglutamine aggregates stimulate ER stress signals and caspase-12 activation.
AB  - Accumulation of unfolded and malfolded proteins causes endoplasmic reticulum (ER)
      stress, stimulating unfolded protein response (UPR) and c-Jun N-terminal kinase
      (JNK) activation and activating caspase-12 located on the ER. Little is known
      about the relationship between the ER stress and polyglutamine [poly(Q)]
      aggregates. Poly(Q)72 repeats [poly(Q)(72)] induced the stimulation of ER stress
      signals such as JNK activation, upregulation of Grp78/Bip and caspase-12
      activation in C2C5 cells. We prepared antiserum against the cleavage site of
      mouse caspase-12 at D(318) (anti-m12D318), and showed that poly(Q)(72) with
      perinuclear aggregates, cytoplasmic inclusions and nuclear inclusions stimulated
      JNK activation and anti-m12D318 immunoreactivity, but poly(Q)(72) with dispersed
      aggregates and small nuclear aggregates showed a significantly less effect.
      Poly(Q)(72) and poly(Q)(11) dispersed in cytoplasm did not. Anti-m12D318-positive
      cells showed apoptotic features. Unlike anti-m8D387 immunoreactivity, the anti
      m12D318 immunoreactivity was not coaggregated with poly(Q). Ac-IETD-fmk (caspase
      8 inhibitor) and Ac-DEVD-CHO (caspase-3 inhibitor) did not prevent the anti
      m12D318 immunoreactivity induced by poly(Q)(72) aggregates. Anti-m12D318
      immunoreactivity was detected in caspase-8(-/-) and caspase-3(-/-) mouse
      embryonic fibroblasts expressing poly(Q)(72) aggregates. Thus, caspase-12 was
      activated by poly(Q)(72) aggregates via a pathway independent of caspase-8 and
      caspase-3 activation, and caspase-12 activation was closely associated with
      poly(Q) aggregate-mediated cell death. Stimulation of ER stress signals may be
      involved in the pathogenesis of neurodegenerative disorders with poly(Q)
      expansion.

PMID- 12045205
TI  - Functional analysis of bone morphogenetic protein type II receptor mutations
      underlying primary pulmonary hypertension.
AB  - A wide range of mutations in the type II receptor for bone morphogenetic protein
      (BMPR-II) have been shown to underlie primary pulmonary hypertension. To
      determine the mechanism of altered BMPR-II function, we employed transient
      transfection studies in cell lines and primary cultures of pulmonary vascular
      smooth muscle cells using green fluorescent protein (GFP)-tagged wild-type and
      mutant BMPR2 constructs and confocal microscopy to localize receptors.
      Substitution of cysteine residues in the ligand binding or kinase domain
      prevented trafficking of BMPR-II to the cell surface, and reduced binding of
      (125)I-BMP4. In addition, transfection of cysteine-substituted BMPR-II markedly
      reduced basal and BMP4-stimulated transcriptional activity of a BMP/Smad
      responsive luciferase reporter gene (3GC2wt-Lux), compared with wild-type BMPR
      II, suggesting a dominant-negative effect of these mutants on Smad signalling. In
      contrast, BMPR-II containing non-cysteine substitutions in the kinase domain were
      localized to the cell membrane, although these also suppressed the activity of
      3GC2wt-Lux. Interestingly, BMPR-II mutations within the cytoplasmic tail
      trafficked to the cell surface, but retained the ability to activate 3GC2wt-Lux.
      Transfection of mutant, but not wild-type, constructs into a mouse epithelial
      cell line (NMuMG cells) led to activation of p38(MAPK) and increased serum
      induced proliferation compared with the wild-type receptor, which was partly
      p38(MAPK)-dependent. We conclude that mutations in BMPR-II heterogeneously
      inhibit BMP/Smad-mediated signalling by diverse molecular mechanisms. However,
      all mutants studied demonstrate a gain of function involving upregulation of
      p38(MAPK)-dependent proproliferative pathways.

PMID- 12045206
TI  - Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32
      domain reminiscent of those at the Prader-Willi/Angelman syndrome region.
AB  - A human imprinted domain at 14q32 contains two co-expressed and reciprocally
      imprinted genes, DLK1 and GTL2, which are expressed from the paternally and
      maternally inherited alleles, respectively. We have previously shown that another
      imprinted locus, on human 15q11-q13, contains a large number of tandemly repeated
      C/D small nucleolar RNA genes (or C/D snoRNAs) only expressed from the paternal
      allele. Here we show that the region downstream from the GTL2 gene is also
      characterized by a transcription unit spanning many repeated intron-encoded C/D
      snoRNA genes, most of them arranged into two tandem arrays of 31 and 9 copies.
      Intriguingly, these snoRNAs depart from previously reported rRNA or snRNA
      methylation guides by their tissue-specific expression and by their lack of
      complementarity to rRNA or snRNA within their sequences. Analysis of the
      orthologous region in the mouse shows that the previously reported maternally
      expressed Rian gene, located downstream of Gtl2 on the distal 12 chromosome,
      encodes at least nine C/D snoRNAs. Through a systematic search in rodents, we
      could identify other C/D snoRNA genes in this domain. All snoRNAs identified on
      mouse distal 12 are brain-specific and only expressed from the maternally
      inherited allele. The human imprinted 14q32 domain therefore shares common
      genomic features with the imprinted 15q11-q13 loci. This link between tandemly
      repeated C/D snoRNA genes and genomic imprinting suggests a role for these
      snoRNAs and/or their host non-coding RNA genes in the evolution and/or mechanism
      of the epigenetic imprinting process.

PMID- 12045207
TI  - Susceptibility loci for atopic dermatitis on chromosomes 3, 13, 15, 17 and 18 in
      a Swedish population.
AB  - Atopic dermatitis is a hereditary, pruritic, inflammatory and chronic skin
      disease that typically presents in early childhood and may continue or recur
      later. The etiology of atopic dermatitis is unknown, but several lines of
      evidence indicate that it is a multifactorial disorder caused by the combined
      influence of genetic and environmental factors, even though the relative
      contributions of genes and environment are not known. To identify important loci
      that contribute to the development of atopic dermatitis, we conducted a genome
      wide linkage analysis with 367 microsatellite markers, using a non-parametric
      affected relative-pair method in 109 pedigrees. Three qualitative phenotypes and
      one semi-quantitative phenotype were studied. For the phenotype atopic
      dermatitis, linkage to chromosome region 3p24-22 was found. For another
      phenotype, atopic dermatitis combined with raised allergen-specific IgE levels, a
      suggestive linkage was found to chromosome region 18q21. For the semi
      quantitative phenotype severity score of atopic dermatitis, suggestive linkage
      was found to chromosome regions 3q14, 13q14, 15q14-15 and 17q21. Identifying
      chromosome regions linked to susceptibility genes for atopic dermatitis provides
      a platform from which the search for atopic dermatitis genes can proceed.

PMID- 12045208
TI  - The 'just-right' signaling model: APC somatic mutations are selected based on a
      specific level of activation of the beta-catenin signaling cascade.
AB  - According to the classical interpretation of Knudson's 'two-hit' hypothesis for
      tumorigenesis, the two 'hits' are independent mutation events, the end result of
      which is loss of a tumor suppressing function. Recently, it has been shown that
      the APC (adenomatous polyposis coli) gene does not entirely follow this model.
      Both the position and type of the second hit in familial adenomatous polyposis
      (FAP) polyps depend on the localization of the germline mutation. This non-random
      distribution of somatic hits has been interpreted as the result of selection for
      more advantageous mutations during tumor formation. However, the APC gene encodes
      for a multifunctional protein, and the exact cellular function upon which this
      selection is based is yet unknown. In this study, we have analyzed somatic APC
      point mutations and loss of heterozygosity (LOH) in 133 colorectal adenomas from
      six FAP patients. We observed that when germline mutations result in truncated
      proteins without any of the seven beta-catenin downregulating 20-amino-acid
      repeats distributed in the central domain of APC, the majority of the
      corresponding somatic point mutations retain one or, less frequently, two of the
      same 20-amino-acid repeats. Conversely, when the germline mutation results in a
      truncated protein retaining one 20-amino-acid repeat, most second hits remove all
      20-amino-acid repeats. The latter is frequently accomplished by allelic loss.
      Notably, and in contrast to previous observations, in a patient where the
      germline APC mutation retains two such repeats, the majority of the somatic hits
      are point mutations (and not LOH) located upstream and removing all of the 20
      amino-acid repeats. These results indicate selection for APC genotypes that are
      likely to retain some activity in downregulating beta-catenin signaling. We
      propose that this selection process is aimed at a specific degree of beta-catenin
      signaling optimal for tumor formation, rather than at its constitutive activation
      by deletion of all of the beta-catenin downregulating motifs in APC.

PMID- 12045209
TI  - Common exon duplication in animals and its role in alternative splicing.
AB  - When searching the genomes of human, fly and worm for cases of exon duplication,
      we found that about 10% of all genes contain tandemly duplicated exons. In the
      course of the analyses, 2438 unannotated exons were identified that are not
      currently included in genome databases and that are likely to be functional. The
      vast majority of them are likely to be involved in mutually exclusive alternative
      splicing events. The common nature of recent exon duplication indicates that it
      might have a significant role in the fast evolution of eukaryotic genes. It also
      provides a general mechanism for the regulation of protein function.

PMID- 12045210
TI  - Loss of phosphatase activity in myotubularin-related protein 2 is associated with
      Charcot-Marie-Tooth disease type 4B1.
AB  - Mutations in the gene encoding myotubularin-related protein 2 (MTMR2) are
      responsible for autosomal recessive Charcot-Marie-Tooth disease type 4B1
      (CMT4B1), a severe hereditary motor and sensory neuropathy characterized by
      focally folded myelin sheaths and demyelination. MTMR2 belongs to the
      myotubularin family, which is characterized by the presence of a phosphatase
      domain. Myotubularin (MTM), the archetype member of this family, is mutated in X
      linked myotubular myopathy. Although MTMR2 and MTM are closely related, they are
      likely to have different functions. Recent studies revealed that MTM
      dephosphorylates specifically phosphatidylinositol 3-phosphate. Here we analyze
      the biochemical properties of the mouse Mtmr2 protein, which shares 97% amino
      acid identity with human MTMR2. We show that phosphatidylinositol-3-phosphate is
      also a substrate for Mtmr2, but, unlike myotubularin, Mtmr2 dephosphorylates
      phosphatidylinositol 3,5-bisphosphate with high efficiency and peak activity at
      neutral pH. We demonstrate that the known disease-associated MTMR2 mutations lead
      to dramatically reduced phosphatase activity, suggesting that the MTMR2
      phosphatase activity is crucial for the proper function of peripheral nerves in
      CMT4B1. Expression analysis of Mtmr2 suggests particularly high levels in
      neurons. Thus, the demyelinating neuropathy CMT4B1 might be triggered by the
      malfunction of neural membrane recycling, membrane trafficking, and/or endocytic
      or exocytotic processes, combined with altered axon-Schwann cell interactions.
      Furthermore, the different biochemical properties of MTM and MTMR2 offer a
      potential explanation for the different human diseases caused by mutations in
      their respective genes.

PMID- 12045211
TI  - Type 2 diabetes is associated with a common mitochondrial variant: evidence from
      a population-based case-control study.
AB  - Variants in mitochondrial DNA (mtDNA) could be associated with type 2 diabetes
      because ATP plays a critical role in the production and release of insulin.
      Diabetes can be precipitated both by mtDNA mutations and by exposure to
      mitochondrial poisons. The risk of inheriting diabetes from an affected mother is
      greater than that from an affected father, but this is not explained by
      maternally inherited diabetes and/or deafness (MIDD) caused by the 3243G : C
      mtDNA point mutation, which accounts for less than 0.5% of cases of diabetes. A
      common mtDNA variant (the 16189 variant) is positively correlated with blood
      fasting insulin, but there are no definitive studies demonstrating that it is
      associated with diabetes. We demonstrated a significant association between the
      16189 variant and type 2 diabetes in a population-based case-control study in
      Cambridgeshire, UK (n=932, odds ratio=1.61 (1.0-2.7, P=0.048), which was greatly
      magnified in individuals with a family history of diabetes from the father's side
      (odds ratio=infinity; P<0.001).

PMID- 12045214
TI  - How to publish in your favorite journal. By Caveman.

PMID- 12045215
TI  - Signalling pathways in oocyte meiotic maturation.

PMID- 12045216
TI  - From Cdc2 to Cdk1: when did the cell cycle kinase join its cyclin partner?
AB  - The idea that Cdc2 and cyclins play a key role in the control of the G2/M
      transition of the cell cycle came largely from genetic analysis of fission yeast
      and physiological studies of clam, frog, sea urchin and starfish eggs and
      oocytes. However, it took a long time to realise that Cdc2 and cyclins form a
      stoichiometric complex and that a cyclin subunit is necessary for the Cdc2
      subunit to gain its protein kinase activity. Cyclins were first recognized as
      proteins whose abundance oscillates during the early cell cycles of marine
      invertebrate eggs and their connection with MPF (maturation-promoting factor),
      the entity defined in frog and starfish oocytes whose activity controls entry
      into M phase, was far from clear at first. Indeed, it was a long time before MPF
      was shown to be a protein kinase, and direct proof that MPF is a heterodimer
      comprising one molecule of cyclin and one molecule of Cdc2 was finally obtained
      only when the Cdc2-associated component of purified starfish MPF was sequenced
      and found to be cyclin B. When this fundamental discovery was confirmed in
      vertebrates and mammalian members of the Cdc2 family were also shown to bind
      cyclins, Cdc2 became Cdk1, the first cyclin-dependent protein kinase.

PMID- 12045217
TI  - Involvement of protein phosphatase-1-mediated MARCKS translocation in myogenic
      differentiation of embryonic muscle cells.
AB  - Myristoylated alanine-rich C kinase substrate (MARCKS) translocates from the
      cytosol to the plasma membrane while mononucleated myoblasts fuse to form
      multinucleated myotubes. Here, we show that protein phosphatase-1-mediated
      dephosphorylation of MARCKS largely influences its subcellular localization and
      the fusion process. Treatment with okadaic acid or tautomycin, which are potent
      inhibitors of protein phosphatases and cell fusion, was found to reversibly block
      the MARCKS translocation. Moreover, the dephosphorylating activity against MARCKS
      markedly increased during myogenesis, and this increase was closely correlated
      with the membrane fusion of the cells. In addition, protein phosphatase-1 was
      identified as a major enzyme that is responsible for dephosphorylation of MARCKS.
      Furthermore, a mutation preventing MARCKS phosphorylation and thus facilitating
      MARCKS translocation resulted in promotion of the cell fusion. In contrast,
      overexpression of MARCKS carrying a mutation that blocks myristoylation and thus
      prevents the MARCKS translocation impaired the myoblast fusion. Together with the
      fact that MARCKS regulates the cytoskeleton dynamics by crosslinking the actin
      filaments in the plasma membrane and that myoblast fusion accompanies massive
      cytoskeleton reorganization, these results suggest that protein phosphatase-1
      mediated MARCKS localization at the membrane is required for the fusion of
      embryonic muscle cells.

PMID- 12045218
TI  - Distinct signals via Rho GTPases and Src drive shape changes by thrombin and
      sphingosine-1-phosphate in endothelial cells.
AB  - Soluble mediators such as thrombin and sphingosine-1-phosphate regulate
      morphological changes in endothelial cells that affect vascular permeability and
      new blood vessel formation. Although these ligands activate a similar set of
      heterotrimeric G proteins, thrombin causes cell contraction and rounding whereas
      sphingosine-1-phosphate induces cell spreading and migration. A functional
      requirement for Rho family GTPases in the cytoskeletal responses to both ligands
      has been established, yet the dynamics of their regulation and additional
      signaling mechanisms that lead to such opposite effects remain poorly understood.
      Using a pull-down assay to monitor the activity of Rho GTPases in human umbilical
      vein endothelial cells, we find significant temporal and quantitative differences
      in RhoA and Rac1 activation. High levels of active RhoA rapidly accumulate in
      cells in response to thrombin whereas Rac1 is inhibited. In contrast, sphingosine
      1-phosphate addition leads to comparatively weak and delayed activation of RhoA
      and it activates Rac1. In addition, we show here that sphingosine-1-phosphate
      treatment activates a Src family kinase and triggers recruitment of the F-actin
      binding protein cortactin to sites of actin polymerization at the rim of membrane
      ruffles. Both Src and Rac pathways are essential for lamellipodia targeting of
      cortactin. Further, Src plays a determinant role in sphingosine-1-phosphate
      induced cell spreading and migration. Taken together these data demonstrate that
      the thrombin-induced contractile and immobile phenotype in endothelial cells
      reflects both robust RhoA activation and Rac inhibition, whereas Src- and Rac
      dependent events couple sphingosine-1-phosphate receptors to the actin
      polymerizing machinery that drives the extension of lamellipodia and cell
      migration.

PMID- 12045219
TI  - Involvement of ASIP/PAR-3 in the promotion of epithelial tight junction
      formation.
AB  - The mammalian protein ASIP/PAR-3 interacts with atypical protein kinase C
      isotypes (aPKC) and shows overall sequence similarity to the invertebrate
      proteins C. elegans PAR-3 and Drosophila Bazooka, which are crucial for the
      establishment of polarity in various cells. The physical interaction between
      ASIP/PAR-3 and aPKC is also conserved in C. elegans PAR-3 and PKC-3 and in
      Drosophila Bazooka and DaPKC. In mammals, ASIP/PAR-3 colocalizes with aPKC and
      concentrates at the tight junctions of epithelial cells, but the biological
      meaning of ASIP/PAR-3 in tight junctions remains to be clarified. In the present
      study, we show that ASIP/PAR-3 staining distributes to the subapical domain of
      epithelial cell-cell junctions, including epithelial cells with less-developed
      tight junctions, in clear contrast with ZO-1, another tight-junction-associated
      protein, the staining of which is stronger in cells with well-developed tight
      junctions. Consistently, immunogold electron microscopy revealed that ASIP/PAR-3
      concentrates at the apical edge of tight junctions, whereas ZO-1 distributes
      alongside tight junctions. To clarify the meaning of this characteristic
      localization of ASIP, we analyzed the effects of overexpressed ASIP/PAR-3 on
      tight junction formation in cultured epithelial MDCK cells. The induced
      overexpression of ASIP/PAR-3, but not its deletion mutant lacking the aPKC
      binding sequence, promotes cell-cell contact-induced tight junction formation in
      MDCK cells when evaluated on the basis of transepithelial electrical resistance
      and occludin insolubilization. The significance of the aPKC-binding sequence in
      tight junction formation is also supported by the finding that the conserved PKC
      phosphorylation site within this sequence, ASIP-Ser827, is phosphorylated at the
      most apical tip of cell-cell contacts during the initial phase of tight junction
      formation in MDCK cells. Together, our present data suggest that ASIP/PAR-3
      regulates epithelial tight junction formation positively through interaction with
      aPKC.

PMID- 12045220
TI  - RyR1 and RyR3 isoforms provide distinct intracellular Ca2+ signals in HEK 293
      cells.
AB  - Ryanodine receptors (RyRs) are expressed on the endoplasmic reticulum of many
      cells, where they form intracellular Ca2+-release channels that participate in
      the generation of intracellular Ca2+ signals. Here we report studies on the
      intracellular localisation and functional properties of transfected RyR1 or RyR3
      channels in HEK 293 cells. Immunofluorescence studies indicated that both RyR1
      and RyR3 did not form clusters but were homogeneously distributed throughout the
      endoplasmic reticulum. Ca2+ release experiments showed that transfected RyR1 and
      RyR3 channels responded to caffeine, although with different sensitivity,
      generating a global release of Ca2+ from the entire endoplasmic reticulum.
      However, video imaging and confocal microscopy analysis revealed that, in RyR3
      expressing cells, local spontaneous Ca2+ release events were observed. No such
      spontaneous activity was observed in RyR1-expressing cells or in control cells.
      Interestingly, the spontaneous release events observed in RyR3-expressing cells
      were restricted to one or two regions of the endoplasmic reticulum, suggesting
      the formation of a further subcellular organisation of RyR3 in Ca2+ release
      units. These results demonstrate that different RyR isoforms can engage in the
      generation of distinct intracellular Ca2+ signals in HEK 293 cells.

PMID- 12045221
TI  - The exosome pathway in K562 cells is regulated by Rab11.
AB  - During maturation, reticulocytes lose some membrane proteins that are not
      required on the mature red cell surface. The proteins are released into the
      extracellular medium associated with vesicles that are formed by budding of the
      endosomal membrane into the lumen of the compartment; this process results in the
      formation of multivesicular bodies (MVBs). Fusion of MVBs with the plasma
      membrane results in secretion of the small internal vesicles, termed exosomes.
      K562 cells release exosomes with similar characteristics to reticulocyte
      exosomes, in particular the transferrin receptor (TfR) is found associated with
      the vesicles. Interestingly, this cell line has been shown to possess high
      amounts of Rab11 compared with other Rab proteins. To assess the regulation of
      transferrin receptor release via exosome secretion by Rab11 in this cell type,
      K562 cells were stably transfected with GFP-Rab11wt or the GTP- and GDP-locked
      mutants. The distribution of the proteins was assessed by fluorescence
      microscopy. Transferrin recycling and the number of TfRs present on the surface
      of the transfected cells were reduced by overexpression of either Rab11wt or the
      mutants. The amount of released exosomes was analyzed by measuring different
      molecular markers present on these vesicles either biochemically or by western
      blot. Overexpression of the dominant-negative mutant Rab11S25N inhibited exosome
      release, whereas the secretion of exosomes was slightly stimulated in cells
      transfected with Rab11wt. Taken together, the results demonstrate that in K562
      cells Rab11 modulates the exosome pathway although the exact step involved is
      still not known.

PMID- 12045222
TI  - Herpes simplex virus type 2 UL14 gene product has heat shock protein (HSP)-like
      functions.
AB  - The HSV-2 UL14 gene encodes a 32 kDa protein that is a minor component of the
      viral tegument. The protein relocates other viral proteins such as VP26 and UL33
      protein into the nuclei of transiently coexpressing cells (Yamauchi et al.,
      2001). We found that the protein shared some characteristics of heat shock
      proteins (HSPs) or molecular chaperones, such as nuclear translocation upon heat
      shock, ATP deprivation and osmotic shock. Interestingly, a significant homology
      over a stretch of 15 amino acids was found between an N-terminal region of HSV
      UL14 protein and the substrate-binding domain of Hsp70 family proteins. Two
      arginine residues in this region were important for nuclear translocation of
      VP26. In addition, overexpression of UL14 protein increased the activity of
      coexpressed firefly luciferase, which suggested that the protein functioned in
      the folding of newly synthesized luciferase. We thus conclude that UL14 protein
      can act as a chaperone-like protein in a singly expressed state.

PMID- 12045223
TI  - GPI anchor transamidase of Trypanosoma brucei: in vitro assay of the recombinant
      protein and VSG anchor exchange.
AB  - GPI8 from Trypanosoma brucei was cloned and expressed in Escherichia coli. TbGPI8
      encodes a 37 kDa protein (35 kDa after removal of the putative signal sequence)
      with a pI of 5.5. It contains one potential N-glycosylation site near the N
      terminus but no C-terminal hydrophobic region. Enzyme activity assays using
      trypanosomal lysates or recombinant TbGpi8 exhibited cleavage of the synthetic
      peptide acetyl-S-V-L-N-aminomethyl-coumarine, indicating that TbGpi8 is indeed
      directly involved in the proteolytic processing of the GPI anchoring signal.
      Intracellular localization of TbGpi8 within tubular structures, such as the
      endoplasmic reticulum, was observed by using specific anti-TbGpi8 antibodies. The
      transamidase mechanism of GPI anchoring was studied in bloodstream forms of
      Trypanosoma brucei using media containing hydrazine or biotinylated hydrazine. In
      the presence of the latter nucleophile, part of the newly formed VSG was linked
      to this instead of the GPI anchor and was not transferred to the cell surface.
      VSG-hydrazine-biotin was detected by streptavidin in western blots and
      intracellularly in Golgi-like compartments.

PMID- 12045224
TI  - Influence of the centrosome in cytokinesis of brown algae: polyspermic zygotes of
      Scytosiphon lomentaria (Scytosiphonales, Phaeophyceae).
AB  - We examined the relationship between the spindle orientation and the
      determination site of cytokinesis in brown algal cells using polyspermic zygotes
      of Scytosiphon lomentaria. When two male gametes fuse with one female gamete, the
      zygote has two pairs of centrioles derived from male gametes and three
      chloroplasts from two male and one female gametes. Just before mitosis, two pairs
      of centrioles duplicate and migrate towards the future mitotic poles. Spindle MTs
      develop and three or four spindle poles are formed. In a tri-polar spindle, one
      pair of centrioles shifts away from the spindle, otherwise, two pairs of
      centrioles exist adjoining at one spindle pole. Chromosomes arrange at several
      equators of the spindle. As a result of these multipolar mitoses, three or four
      daughter nuclei developed. Subsequently, these daughter nuclei form a line along
      the long axis of the cell. Cell partition always takes place between daughter
      nuclei, perpendicular to the long axis of the cell. Three or four daughter cells
      are produced by cytokinesis. Some of the daughter cells after cytokinesis do not
      have a nucleus, but all of them always contain the centrosome and chloroplast.
      Therefore, the number of daughter cells always coincides with the number of
      centrosomes or microtubule organizing centers (MTOCs). These results show that
      the cytokinetic plane in the brown algae is determined by the position of
      centrosomes after mitosis and is not dependent on the spindle position.

PMID- 12045225
TI  - Mechanisms for targeting of the Saccharomyces cerevisiae GPI-anchored cell wall
      protein Crh2p to polarised growth sites.
AB  - The cell wall is an essential structure that preserves the osmotic integrity of
      fungal cells and determines cellular morphology during developmental programs.
      The high number of different wall components demands a variety of processes to
      deliver precursors and synthetic proteins to the proper location at the right
      time for wall development and modification. Here, the specificity of the
      mechanisms that regulate the temporal and spatial localisation of cell wall
      proteins to sites of polarised growth in Saccharomyces cerevisiae is
      investigated. For this purpose, the localisation of Crh2p, a cell wall
      glycosylphosphatidylinositol (GPI)-anchored mannoprotein that we have recently
      described as involved in cell wall construction and localised to polarised growth
      sites, was followed using a Crh2p-GFP fusion protein. Crh2p distribution was
      studied in several genetic backgrounds affected in different steps of the cell
      polarity establishment machinery or/and bud morphogenesis. Crh2p is localised at
      the mother-bud neck in bud1 cells following the random budding pattern
      characteristic of this mutant. The Crh2p distribution was greatly altered in a
      cdc42-1 mutant, indicating complete dependence on an organised actin cytoskeleton
      for polarised Crh2p distribution. The usual deposition of Crh2p in a ring at the
      base of growing buds was lacking in cdc10-11 cells growing under restrictive
      temperature conditions, whereas Crh2p deposition at the septum region was absent
      in both cdc10-11 and cdc15-lyt1 cells. These results point to the dependence of
      Crh2p localisation at the bud-neck on both septins and septum integrity.
      Furthermore, in the absence of Bni4p, a scaffold protein involved in the
      targeting of the chitin synthase III complex to the bud neck, Crh2p was not
      longer found at the neck in large-budded cells undergoing cytokinesis. Finally,
      Crh2p was not properly localised in cells deleted in CHS5, which encodes a
      protein involved in the transport of Chs3p, and was completely mislocalised in
      sbe2/sbe22 mutants, suggesting that the transport systems for Chs3p and Crh2p are
      to a certain extent coincident. The transport of other GPI-cell wall proteins,
      such as Cwp1p, however, does not depend on these systems as the localisation of
      the latter protein was not affected in either of these mutants.

PMID- 12045226
TI  - Mice overexpressing placenta growth factor exhibit increased vascularization and
      vessel permeability.
AB  - Placenta growth factor (PlGF) is a member of the vascular endothelial growth
      factor (VEGF) family, comprising at least five cytokines specifically involved in
      the regulation of vascular and/or lymphatic endothelium differentiation. Several
      lines of evidence indicate a role for PlGF in monocyte chemotaxis and in
      potentiating the activity of VEGF, but the exact function of this cytokine is not
      fully understood. To define the biological role of PlGF in vivo, we have produced
      a transgenic mouse model overexpressing this factor in the skin by using a
      keratin 14 promoter cassette. Our data indicate that PlGF has strong angiogenic
      properties in both fetal and adult life. PlGF overexpression results in a
      substantial increase in the number, branching and size of dermal blood vessels as
      well as in enhanced vascular permeability. Indeed, intradermally injected
      recombinant PlGF was able to induce vessel permeability in wild-type mice. The
      analysis of vascular endothelial growth factor receptor 1/flt-1 and vascular
      endothelial growth factor receptor 2/flk-1 indicates that the two receptors are
      induced in the skin endothelium of transgenic mice suggesting that both are
      involved in mediating the effect of overexpressed PlGF.

PMID- 12045227
TI  - Rho-dependent and -independent activation mechanisms of ezrin/radixin/moesin
      proteins: an essential role for polyphosphoinositides in vivo.
AB  - Ezrin/radixin/moesin (ERM) proteins crosslink actin filaments to plasma membranes
      and are involved in the organization of the cortical cytoskeleton, especially in
      the formation of microvilli. ERM proteins are reported to be activated as
      crosslinkers in a Rho-dependent manner and are stabilized when phosphorylated at
      their C-terminal threonine residue to create C-terminal threonine-phosphorylated
      ERM proteins (CPERMs). Using a CPERM-specific mAb, we have shown, in vivo, that
      treatment with C3 transferase (a Rho inactivator) or staurosporine (a protein
      kinase inhibitor) leads to the dephosphorylation of CPERMs, the translocation of
      ERM proteins from plasma membranes to the cytoplasm and microvillar breakdown. We
      further elucidated that ERM protein activation does not require C-terminal
      phosphorylation in A431 cells stimulated with epidermal growth factor. In certain
      types of kidney-derived cells such as MDCK cells, however, ERM proteins appear to
      be activated in the absence of Rho activation and remain active without C
      terminal phosphorylation. Interestingly, microinjection of an aminoglycoside
      antibiotic, neomycin, which binds to polyphosphoinositides, such as
      phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], affected the
      activation of ERM proteins regardless of cell type. These findings not only
      indicate the existence of a Rho-independent activation mechanism of ERM proteins
      but also suggest that both Rho-dependent and -independent activation of ERM
      proteins require a local elevation of PtdIns(4,5)P(2) concentration in vivo.

PMID- 12045228
TI  - Trimers of the fibronectin cell adhesion domain localize to actin filament
      bundles and undergo rearward translocation.
AB  - Previous studies have shown that small beads coated with FN7-10, a four-domain
      cell adhesion fragment of fibronectin, bind to cell surfaces and translocate
      rearward. Here we investigate whether soluble constructs containing two to five
      FN7-10 units might be sufficient for activity. We have produced a monomer, three
      forms of dimers, a trimer and a pentamer of FN7-10, on the end of spacer arms.
      These oligomers could bind small clusters of up to five integrins. Fluorescence
      microscopy showed that the trimer and pentamer bound strongly to the cell
      surface, and within 5 minutes were prominently localized to actin fiber bundles.
      Monomers and dimers showed only diffuse localization. Beads coated with a low
      concentration (probably one complex per bead) of trimer or pentamer showed
      prolonged binding and rearward translocation, presumably with the translocating
      actin cytskeleton. Beads containing monomer or dimer showed only brief binding
      and diffusive movements. We conclude that clusters of three integrin-binding
      ligands are necessary and sufficient for coupling to and translocating with the
      actin cytoskeleton.

PMID- 12045229
TI  - Ras induces NBT-II epithelial cell scattering through the coordinate activities
      of Rac and MAPK pathways.
AB  - Cell dissociation and cell migration are the two main components of epithelium
      mesenchyme transitions (EMT). We previously demonstrated that Ras is required for
      the accomplishment of both of these processes during the EGF-induced EMT of the
      NBT-II rat carcinoma cell line in vitro. In this study, we examined the
      downstream targets of Ras that are responsible for the dissociation and motility
      of NBT-II cells. Overexpression of activated forms of c-Raf and MEK1 (a component
      of the mitogen-activated protein kinase pathway, MAPK) led to cell dissociation,
      as inferred by the loss of desmosomes from the cell periphery. By contrast,
      active PI3K, RalA and RalB did not induce desmosome breakdown. The MEK1 inhibitor
      PD098059 inhibited EGF- and Ras-induced cell dispersion, whereas the PI3K
      inhibitor LY294002 had no effect. Accordingly, among the partial loss-of-function
      mutants of Ras (RasV12) that were used to distinguish between downstream targets
      of Ras, we found that the Raf-specific Ras mutants RasV12S35 and RasV12E38
      induced cell dissociation. The PI3K- and RalGDS-activating Ras mutants had, in
      contrast, no effect on cell dispersion. However, MEK1 was unable to promote cell
      motility, whereas RasV12S35 and RasV12E38 induced cell migration, suggesting that
      another Ras effector was responsible for cell motility. We found that the small
      GTPase Rac is necessary for EGF-mediated cell dispersion since overexpression of
      a dominant-negative mutant of Rac1 (Rac1N17) inhibited EGF-induced NBT-II cell
      migration. All stimuli that promoted cell migration also induced Rac activation.
      Finally, coexpression of active Rac1 and active MEK1 induced the motility of NBT
      II cells, suggesting that Ras mediates NBT-II cell scattering through the
      coordinate activation of Rac and the Raf/MAPK pathway.

PMID- 12045230
TI  - Mediators of innate immune recognition of bacteria concentrate in lipid rafts and
      facilitate lipopolysaccharide-induced cell activation.
AB  - The plasma membrane of cells is composed of lateral heterogeneities, patches and
      microdomains. These membrane microdomains or lipid rafts are enriched in
      glycosphingolipids and cholesterol and have been implicated in cellular processes
      such as membrane sorting and signal transduction. In this study we investigated
      the importance of lipid raft formation in the innate immune recognition of
      bacteria using biochemical and fluorescence imaging techniques. We found that
      receptor molecules that are implicated in lipopolysaccharide (LPS)-cellular
      activation, such as CD14, heat shock protein (hsp) 70, 90, Chemokine receptor 4
      (CXCR4), growth differentiation factor 5 (GDF5) and Toll-like receptor 4 (TLR4),
      are present in microdomains following LPS stimulation. Lipid raft integrity is
      essential for LPS-cellular activation, since raft-disrupting drugs, such as
      nystatin or MCD, inhibit LPS-induced TNF-alpha secretion. Our results suggest
      that the entire bacterial recognition system is based around the ligation of CD14
      by bacterial components and the recruitment of multiple signalling molecules,
      such as hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation,
      within the lipid rafts.

PMID- 12045233
TI  - Distinct mechanosensitive properties of capsaicin-sensitive and -insensitive
      sensory neurons.
AB  - Mechanical stimulation of the somata of cultured neonatal rat dorsal root ganglia
      (DRG) neurons evoked inward cationic currents that displayed distinct properties
      between different subsets of cells. The presumptive nociceptor population,
      defined by capsaicin sensitivity, showed higher thresholds for the induction of
      an inward current and lower peak currents than other mechanosensitive neurons. A
      subset of capsaicin-sensitive IB4-positive sensory neurons was refractory to
      mechanical stimulation. All mechanically activated currents were blocked by
      gadolinium (IC50 approximately 8 microm) and ruthenium red (IC50 approximately 3
      microm). Disruption of the actin cytoskeleton by acute application of 10 microm
      cytochalasin B inhibited currents much more effectively in capsaicin-insensitive
      (61%) than capsaicin-sensitive neurons (20%). Extracellular calcium also
      attenuated mechanosensitive currents and to a greater degree in capsaicin
      insensitive neurons than capsaicin-sensitive neurons. These data demonstrate that
      the somata of different types of cultured sensory neurons have distinct
      mechanosensitive phenotypes that retain properties associated with nerve terminal
      mechanosensors in vivo.

PMID- 12045234
TI  - Muscarinic M2 receptors on peripheral nerve endings: a molecular target of
      antinociception.
AB  - We recently described a novel endogenous mechanism of peripheral antinociception,
      possibly involving activation of muscarinic M2 acetylcholine receptors that are
      expressed on nociceptive nerve endings and decrease their sensitivity. In the
      present study, this mechanism was scrutinized in skin taken from mice with
      targeted deletions of the muscarinic M2 receptor gene and, for control purposes,
      of the M4 receptor gene. Two different approaches were taken.
      Electrophysiologically the effects of muscarine on nociceptive afferents were
      investigated using the mouse skin-saphenous nerve preparation, in vitro.
      Muscarine did not excite nociceptors in the wild-type littermates (WT) and M4
      knock-out (M4 KO) mice, but almost all fibers exhibited marked desensitization to
      mechanical and heat stimuli. Surprisingly, in the M2 KO mice, muscarine was able
      to excite C-nociceptors and to induce a mild sensitization to heat but caused no
      alteration in mechanical responsiveness tested with von Frey hairs. In the
      second, neurochemical approach, the heat-induced cutaneous release of calcitonin
      gene-related peptide (CGRP) was investigated to gain comparative data on the
      neurosecretory (vasodilatory) functions of the primary afferent neurons. The
      substantial increase of CGRP release evoked by noxious heat (47 degrees C) was
      diminished under muscarine by >50% in the WT and M4 KO animals but remained
      unaltered in the M2 KO mice. Together, these data provide direct evidence that M2
      receptors on cutaneous nerve endings mediate effective depression of nociceptive
      responsiveness. This observation should be of interest for the development of
      novel classes of analgesic agents.

PMID- 12045235
TI  - Two-state membrane potential transitions of striatal spiny neurons as evidenced
      by numerical simulations and electrophysiological recordings in awake monkeys.
AB  - Spontaneous membrane potential fluctuations of striatal spiny projection neurons
      play a crucial role in their spike generation. Previous intracellular recording
      studies in anesthetized rats have shown that the membrane potential of striatal
      spiny neurons shifts between the depolarized "up" state and the hyperpolarized
      "down" state. Here we report evidence for the occurrence of such two-state
      membrane potential transitions by numerical simulations and electrophysiological
      recordings in awake monkeys. Data from our simulations of a striatal spiny neuron
      model demonstrated that spike latency histograms of the model neuron displayed
      two separate (i.e., early and late) peaks in response to excitatory cortical
      input, corresponding to neuronal activity in the up or down state, respectively.
      Then, we addressed experimentally whether the latency distribution of cortically
      induced spike firing of striatal spiny neurons might show dual peaks. Striatal
      neuron activity was extracellularly recorded in response to electrical
      stimulation in the two cortical motor-related areas, the primary motor cortex and
      the supplementary motor area, of awake monkeys. Analysis of spike latency
      histograms has defined that striatal spiny neurons typically exhibit two
      temporally distinct peaks, as obtained by the numerical simulations. Thus, the
      membrane potential shifts between the up and down states appear to occur in
      striatal spiny neurons of the behaving animal.

PMID- 12045236
TI  - Essential and instructive roles of GATA factors in eosinophil development.
AB  - GATA transcription factors are major regulators of hematopoietic and immune
      system. Among GATA factors, GATA-1, GATA-2, and GATA-3 play crucial roles in the
      development of erythroid cells, hematopoietic stem, and progenitor cells, and T
      helper type 2 (Th2) cells, respectively. A high level of GATA-1 and GATA-2
      expression has been observed in eosinophils, but their roles in eosinophil
      development remain uncertain both in vitro and in vivo. Here we show that
      enforced expression of GATA-1 in human primary myeloid progenitor cells
      completely switches myeloid cell fate into eosinophils. Expression of GATA-1
      exclusively promotes development and terminal maturation of eosinophils.
      Functional domain analyses revealed that the COOH-terminal finger is essential
      for this capacity while the other domains are dispensable. Importantly, GATA-1
      deficient mice failed to develop eosinophil progenitors in the fetal liver. On
      the other hand, GATA-2 also showed instructive capacity comparable to GATA-1 in
      vitro and efficiently compensated for GATA-1 deficiency in terms of eosinophil
      development in vivo, indicating that proper accumulation of GATA factors is
      critical for eosinophil development. Taken together, our findings establish
      essential and instructive roles of GATA factors in eosinophil development. GATA-1
      and GATA-2 could be novel molecular targets for therapeutic approaches to
      allergic inflammation.

PMID- 12045237
TI  - Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter
      leads to selective loss of the eosinophil lineage in vivo.
AB  - Transcription factor GATA-1 reprograms immature myeloid cells to three different
      hematopoietic lineages-erythroid cells, megakaryocytes, and eosinophils. GATA-1
      is essential for maturation of erythroid and megakaryocytic precursors, as
      revealed by gene targeting in mice. Here we demonstrate that deletion of a high
      affinity GATA-binding site in the GATA-1 promoter, an element presumed to mediate
      positive autoregulation of GATA-1 expression, leads to selective loss of the
      eosinophil lineage. These findings suggest that GATA-1 is required for
      specification of this lineage during hematopoietic development. Mice lacking the
      ability to produce eosinophils should prove useful in ascertaining the role of
      eosinophils in a variety of inflammatory or allergic disorders.

PMID- 12045238
TI  - Identification of a mutated fibronectin as a tumor antigen recognized by CD4+ T
      cells: its role in extracellular matrix formation and tumor metastasis.
AB  - CD4+ T cells play an important role in orchestrating host immune responses
      against cancer, particularly by providing critical help for priming and extending
      the survival of CD8+ T cells. However, relatively little is known about major
      histocompatibility complex class II-restricted human tumor antigens capable of
      activating CD4+ T cells. Here, we describe the identification of a mutated
      fibronectin (FN) as a tumor antigen recognized by human histocompatibility
      leukocyte antigen-DR2-restricted CD4+ T cells. Deoxyribonucleic acid (DNA)
      sequencing analysis indicated that this gene contains a mutation that results in
      the substitution of lysine for glutamic acid and gives rise to a new T cell
      epitope recognized by CD4+ T cells. Tumor cells harboring the mutant FN resulted
      in the loss of FN matrix formation and the gain of metastatic potential based on
      the migration pattern compared with that of tumor cells that express wild-type
      FN. Additional experiments using cell lines stably expressing the mutated FN cDNA
      demonstrated that the point mutation in FN was responsible for the loss of FN
      staining in extracellular matrices and the enhancement of tumor cell migration.
      These findings represent the first demonstration that a mutated gene product
      recognized by CD4+ T cells is directly involved in tumor metastasis, which
      indicates the importance of CD4+ T cells in controlling the spread of tumor cells
      to distant anatomic sites.

PMID- 12045239
TI  - CD8(+) T cell tolerance to a tumor-associated antigen is maintained at the level
      of expansion rather than effector function.
AB  - CD8+ T cell tolerance to self-proteins prevents autoimmunity but represents an
      obstacle to generating T cell responses to tumor-associated antigens. We have
      made a T cell receptor (TCR) transgenic mouse specific for a tumor antigen and
      crossed TCR-TG mice to transgenic mice expressing the tumor antigen in
      hepatocytes (gag-TG). TCRxgag mice showed no signs of autoimmunity despite
      persistence of high avidity transgenic CD8+ T cells in the periphery. Peripheral
      CD8+ T cells expressed phenotypic markers consistent with antigen encounter in
      vivo and had upregulated the antiapoptotic molecule Bcl-2. TCRxgag cells failed
      to proliferate in response to antigen but demonstrated cytolytic activity and the
      ability to produce interferon gamma. This split tolerance was accompanied by
      inhibition of Ca(2+) flux, ERK1/2, and Jun kinase phosphorylation, and a block in
      both interleukin 2 production and response to exogenous interleukin 2. The data
      suggest that proliferation and expression of specific effector functions
      characteristic of reactive cells are not necessarily linked in CD8+ T cell
      tolerance.

PMID- 12045240
TI  - Involvement of the TCR Cbeta FG loop in thymic selection and T cell function.
AB  - The asymmetric disposition of T cell receptor (TCR) Cbeta and Calpha ectodomains
      creates a cavity with a side-wall formed by the rigid Cbeta FG loop. To
      investigate the significance of this conserved structure, we generated loop
      deletion (betaDeltaFG) and betawt transgenic (tg) mice using the TCR beta subunit
      of the N15 CTL. N15betawt and N15betaDeltaFG H-2(b) animals have comparable
      numbers of thymocytes in S phase and manifest developmental progression through
      the CD4(-)CD8(-) double-negative (DN) compartment. N15betaDeltaFG facilitates
      transition from DN to CD4(+)8(+) double-positive (DP) thymocytes in recombinase
      activating gene (RAG)-2(-/-) mice, showing that pre-TCR function remains.
      N15betaDeltaFG animals possess approximately twofold more CD8(+) single-positive
      (SP) thymocytes and lymph node T cells, consistent with enhanced positive
      selection. As an altered Valpha repertoire observed in N15betaDeltaFG mice may
      confound the deletion's effect, we crossed N15alphabeta TCR tg RAG-2(-/-) with
      N15betaDeltaFG tg RAG-2(-/-) H-2(b) mice to generate N15alphabeta RAG-2(-/-) and
      N15alphabeta.betaDeltaFG RAG-2(-/-) littermates. N15alphabeta.betaDeltaFG RAG-2(
      /-) mice show an 8-10-fold increase in DP thymocytes due to reduced negative
      selection, as evidenced by diminished constitutive and cognate peptide-induced
      apoptosis. Compared with N15alphabeta, N15alphabeta.betaDeltaFG T cells respond
      poorly to cognate antigens and weak agonists. Thus, the Cbeta FG loop facilitates
      negative selection of thymocytes and activation of T cells.

PMID- 12045241
TI  - Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of
      both IL-5 and eotaxin precludes the development of eosinophilia and airways
      hyperreactivity in experimental asthma.
AB  - Interleukin (IL)-5 and IL-13 are thought to play key roles in the pathogenesis of
      asthma. Although both cytokines use eotaxin to regulate eosinophilia, IL-13 is
      thought to operate a separate pathway to IL-5 to induce airways hyperreactivity
      (AHR) in the allergic lung. However, identification of the key pathway(s) used by
      IL-5 and IL-13 in the disease process is confounded by the failure of anti-IL-5
      or anti-IL-13 treatments to completely inhibit the accumulation of eosinophils in
      lung tissue. By using mice deficient in both IL-5 and eotaxin (IL-5/eotaxin(-/-))
      we have abolished tissue eosinophilia and the induction of AHR in the allergic
      lung. Notably, in mice deficient in IL-5/eotaxin the ability of CD4(+) T helper
      cell (Th)2 lymphocytes to produce IL-13, a critical regulator of airways smooth
      muscle constriction and obstruction, was significantly impaired. Moreover, the
      transfer of eosinophils to IL-5/eotaxin(-/-) mice overcame the intrinsic defect
      in T cell IL-13 production. Thus, factors produced by eosinophils may either
      directly or indirectly modulate the production of IL-13 during Th2 cell
      development. Our data show that IL-5 and eotaxin intrinsically modulate IL-13
      production from Th2 cells and that these signaling systems are not necessarily
      independent effector pathways and may also be integrated to regulate aspects of
      allergic disease.

PMID- 12045242
TI  - NadA, a novel vaccine candidate of Neisseria meningitidis.
AB  - Neisseria meningitidis is a human pathogen, which, in spite of antibiotic
      therapy, is still a major cause of mortality due to sepsis and meningitis. Here
      we describe NadA, a novel surface antigen of N. meningitidis that is present in
      52 out of 53 strains of hypervirulent lineages electrophoretic types (ET) ET37,
      ET5, and cluster A4. The gene is absent in the hypervirulent lineage III, in N.
      gonorrhoeae and in the commensal species N. lactamica and N. cinerea. The
      guanine/cytosine content, lower than the chromosome, suggests acquisition by
      horizontal gene transfer and subsequent limited evolution to generate three well
      conserved alleles. NadA has a predicted molecular structure strikingly similar to
      a novel class of adhesins (YadA and UspA2), forms high molecular weight
      oligomers, and binds to epithelial cells in vitro supporting the hypothesis that
      NadA is important for host cell interaction. NadA induces strong bactericidal
      antibodies and is protective in the infant rat model suggesting that this protein
      may represent a novel antigen for a vaccine able to control meningococcal disease
      caused by three hypervirulent lineages.

PMID- 12045243
TI  - The contribution of accessory toxins of Vibrio cholerae O1 El Tor to the
      proinflammatory response in a murine pulmonary cholera model.
AB  - The contribution of accessory toxins to the acute inflammatory response to Vibrio
      cholerae was assessed in a murine pulmonary model. Intranasal administration of
      an El Tor O1 V. cholerae strain deleted of cholera toxin genes (ctxAB) caused
      diffuse pneumonia characterized by infiltration of PMNs, tissue damage, and
      hemorrhage. By contrast, the ctxAB mutant with an additional deletion in the
      actin-cross-linking repeats-in-toxin (RTX) toxin gene (rtxA) caused a less severe
      pathology and decreased serum levels of proinflammatory molecules interleukin
      (IL)-6 and murine macrophage inflammatory protein (MIP)-2. These data suggest
      that the RTX toxin contributes to the severity of acute inflammatory responses.
      Deletions within the genes for either hemagglutinin/protease (hapA) or hemolysin
      (hlyA) did not significantly affect virulence in this model. Compound deletion of
      ctxAB, hlyA, hapA, and rtxA created strain KFV101, which colonized the lung but
      induced pulmonary disease with limited inflammation and significantly reduced
      serum titers of IL-6 and MIP-2. 100% of mice inoculated with KFV101 survive,
      compared with 20% of mice inoculated with the ctxAB mutant. Thus, the reduced
      virulence of KFV101 makes it a prototype for multi-toxin deleted vaccine strains
      that could be used for protection against V. cholerae without the adverse effects
      of the accessory cholera toxins.

PMID- 12045244
TI  - Treatment with soluble interleukin-15Ralpha exacerbates intracellular parasitic
      infection by blocking the development of memory CD8+ T cell response.
AB  - Interferon (IFN)-gamma-producing CD8+ T cells are important for the successful
      resolution of the obligate intracellular parasite Toxoplasma gondii by preventing
      the reactivation or controlling a repeat infection. Previous reports from our
      laboratory have shown that exogenous interleukin (IL)-15 treatment augments the
      CD8+ T cell response against the parasite. However, the role of endogenous IL-15
      in the proliferation of activated/memory CD8+ T cells during toxoplasma or any
      other infection is unknown. In this study, we treated T. gondii immune mice with
      soluble IL-15 receptor alpha (sIL-15Ralpha) to block the host endogenous IL-15.
      The treatment markedly reduced the ability of the immune animals to control a
      lethal infection. CD8+ T cell activities in the sIL-15Ralpha-administered mice
      were severely reduced as determined by IFN-gamma release and target cell lysis
      assays. The loss of CD8+ T cell immunity due to sIL-15Ralpha treatment was
      further demonstrated by adoptive transfer experiments. Naive recipients
      transferred with CD44(hi) activated/memory CD8+ T cells and treated with sIL
      15Ralpha failed to resist a lethal T. gondii infection. Moreover, sIL-15Ralpha
      treatment of the recipients blocked the ability of donor CD44(hi)
      activated/memory CD8+ T cells to replicate in response to T. gondii challenge. To
      our knowledge, this is the first demonstration of the important role of host IL
      15 in the development of antigen-specific memory CD8+ T cells against an
      intracellular infection.

PMID- 12045245
TI  - CD4+ T cells regulate surgical and postinfectious adhesion formation.
AB  - The development of adhesions in the peritoneal and pelvic cavities, which
      commonly form after surgery or infection, cause significant morbidity and
      mortality. However, the pathogenesis of adhesion formation is still poorly
      understood. Because T cells are important in orchestrating fibrinogenic tissue
      disorders, we hypothesized that they play a critical role in the pathogenesis of
      peritoneal adhesion formation. Using a cecal abrasion surgical model in rodents,
      T cell depletion and adoptive transfer experiments demonstrated that this host
      response is dependent on CD4+ alphabeta T cells. These cells were also critical
      to adhesion formation associated with experimental intraabdominal sepsis. T cell
      transfer studies with mice deficient in signal transducer and activator of
      transcription (Stat)4 and Stat6 revealed that adhesion formation was dependent on
      a T helper 1 response. Activated T cells homed to the peritoneal cavity 6 hours
      after cecal abrasion surgery and predominated at this site during adhesiogenesis.
      Increased levels of the T cell-derived proinflammatory cytokine interleukin (IL)
      17 and of neutrophil chemoattractant CXC chemokines macrophage inflammatory
      protein-2/CXCL8 and cytokine-induced neutrophil chemoattractant/CXCL1 were
      associated with adhesion formation. The production of these chemokines was
      dependent on T cells. Furthermore, the administration of neutralizing antibodies
      specific for IL-17 or the receptor that binds these CXC chemokines, CXC chemokine
      receptor 2, significantly reduced the degree of adhesion formation. These results
      demonstrate for the first time that the immunopathogenesis of adhesion formation
      is under the control of T cells and that T cell-derived cytokines and chemokines
      play important roles in the development of this deleterious host response.

PMID- 12045246
TI  - Inhibition of methylcholanthrene-induced carcinogenesis by an interferon gamma
      receptor-dependent foreign body reaction.
AB  - The foreign body reaction is one of the oldest host defense mechanisms against
      tissue damage which involves inflammation, scarring, and encapsulation. The
      chemical carcinogen methylcholanthrene (MCA) induces fibrosarcoma and tissue
      damage in parallel at the injection site. Tumor development induced by MCA but
      not due to p53-deficiency is increased in interferon-gamma receptor (IFN-gammaR)
      deficient mice. In the absence of IFN-gammaR, MCA diffusion and DNA damage of
      surrounding cells is increased. Locally produced IFN-gamma induces the formation
      of a fibrotic capsule. Encapsulated MCA can persist virtually life-long in mice
      without inducing tumors. Together, the foreign body reaction against MCA prevents
      malignant transformation, probably by reducing DNA damage. This mechanism is more
      efficient in the presence of IFN-gammaR. Our results indicates that inflammation
      and scarring, both suspected to contribute to malignancy, prevent cancer in
      certain situations.

PMID- 12045247
TI  - A unique subset of self-specific intraintestinal T cells maintains gut integrity.
AB  - Lymphocytes residing in the intestinal epithelium are exclusively T cells and
      account for one of the largest collection of T cells in the organism. However,
      their function remains obscure. We and others have shown that the development of
      intestinal intraepithelial T cells is compromised in mutant mice prone to chronic
      intestinal inflammation. These results led us to directly assess their role in
      regulating the development of colitis secondary to transfer of primary splenic
      TCRalphabeta(+)CD4(+)CD45RB(hi) T cells into severe combined immunodeficiency
      (SCID) mice. Here we demonstrate that prior reconstitution of SCID recipients
      with intraintestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells prevents
      disease, and does so in an interleukin (IL)-10-dependent fashion. In contrast,
      reconstitution with either TCRgammadelta(+) or TCRalphabeta(+)CD4(-)
      CD8alpha(+)beta(+) intestinal T cells did not prevent colitis.
      TCRalphabeta(+)CD4(-)8alpha(+)beta(-) T cells are unique to the intestinal
      epithelium of both rodents and humans. Previous repertoire analyses of
      TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells revealed a high proportion of
      cells expressing high affinity, self-specific TCR within this subset. We
      demonstrate that monoclonal, self specific TCRalphabeta(+)CD4(-)CD8alpha(+)beta(
      ) cells derived from TCR transgenic mice also prevent the onset of colitis. Thus,
      intestinal TCRalphabeta(+)CD4(-)CD8alpha(+)beta(-) T cells, selected based on
      their self-reactivity, maintain gut integrity in a IL-10-dependent fashion.

PMID- 12045248
TI  - Mechanism of transforming growth factor beta-induced inhibition of T helper type
      1 differentiation.
AB  - Regulation by transforming growth factor (TGF)-beta plays an important role in
      immune homeostasis. TGF-beta inhibits T cell functions by blocking both
      proliferation and differentiation. Here we show that TGF-beta blocks Th1
      differentiation by inhibiting the expression of T-bet, the apparent
      masterregulator of T helper (Th)1 differentiation. Restoration of T-bet
      expression through retroviral transduction of T-bet into developing Th1 cells
      abrogated the inhibitory effect of TGF-beta. In addition, we show that, contrary
      to prior suggestions, downregulation of interleukin 12 receptor beta2 chain is
      not key to the TGF-beta-mediated effect. Furthermore, we show that the direct
      inhibitory effect of TGF-beta on T cells is responsible, at least in part, for
      the inability of BALB/c mice to mount a Leishmania-specific Th1 response and to
      clear Leishmanial infection.

PMID- 12045249
TI  - Interferon-alpha and interleukin-12 are induced differentially by Toll-like
      receptor 7 ligands in human blood dendritic cell subsets.
AB  - Dendritic cells (DCs) play a crucial role in the immune responses against
      infections by sensing microbial invasion through toll-like receptors (TLRs). In
      humans, two distinct DC subsets, CD11c(-) plasmacytoid DCs (PDCs) and CD11c(+)
      myeloid DCs (MDCs), have been identified and can respond to different TLR
      ligands, depending on the differential expression of cognate TLRs. In this study,
      we have examined the effect of TLR-7 ligands on human DC subsets. Both subsets
      expressed TLR-7 and could respond to TLR-7 ligands, which enhanced the survival
      of the subsets and upregulated the surface expression of costimulatory molecules
      such as CD40, CD80, and CD86. However, the cytokine induction pattern was
      distinct in that PDCs and MDCs produced interferon (IFN)-alpha and interleukin
      (IL)-12, respectively. In response to TLR-7 ligands, the Th1 cell supporting
      ability of both DC subsets was enhanced, depending on the cytokines the
      respective subsets produced. This study demonstrates that TLR-7 exerts its
      biological effect in a DC subset-specific manner.

PMID- 12045250
TI  - Making eosinophils through subtle shifts in transcription factor expression.

PMID- 12045251
TI  - Aquaporin water channels: atomic structure molecular dynamics meet clinical
      medicine.

PMID- 12045252
TI  - The thyroid axis just got more complicated.

PMID- 12045253
TI  - Acinar-to-ductal metaplasia in pancreatic cancer development.

PMID- 12045254
TI  - Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast
      lineage and is critically involved in bone repair.
AB  - Preclinical and clinical studies suggest a possible role for cyclooxygenases in
      bone repair and create concerns about the use of nonsteroidal antiinflammatory
      drugs in patients with skeletal injury. We utilized wild-type, COX-1(-/-), and
      COX-2(-/-) mice to demonstrate that COX-2 plays an essential role in both
      endochondral and intramembranous bone formation during skeletal repair. The
      healing of stabilized tibia fractures was significantly delayed in COX-2(-/-)
      mice compared with COX-1(-/-) and wild-type controls. The histology was
      characterized by a persistence of undifferentiated mesenchyme and a marked
      reduction in osteoblastogenesis that resulted in a high incidence of fibrous
      nonunion in the COX-2(-/-) mice. Similarly, intramembranous bone formation on the
      calvaria was reduced 60% in COX-2(-/-) mice following in vivo injection of FGF-1
      compared with either COX-1(-/-) or wild-type mice. To elucidate the mechanism
      involved in reduced bone formation, osteoblastogenesis was studied in bone marrow
      stromal cell cultures obtained from COX-2(-/-) and wild-type mice. Bone nodule
      formation was reduced 50% in COX-2(-/-) mice. The defect in osteogenesis was
      completely rescued by addition of prostaglandin E2 (PGE(2)) to the cultures. In
      the presence of bone morphogenetic protein (BMP-2), bone nodule formation was
      enhanced to a similar level above that observed with PGE(2) alone in both control
      and COX-2(-/-) cultures, indicating that BMPs complement COX-2 deficiency and are
      downstream of prostaglandins. Furthermore, we found that the defect in COX-2(-/-)
      cultures correlated with significantly reduced levels of cbfa1 and osterix, two
      genes necessary for bone formation. Addition of PGE(2) rescued this defect, while
      BMP-2 enhanced cbfa1 and osterix in both COX-2(-/-) and wild-type cultures.
      Finally, the effects of these agents were additive, indicating that COX-2 is
      involved in maximal induction of osteogenesis. These results provide a model
      whereby COX-2 regulates the induction of cbfa1 and osterix to mediate normal
      skeletal repair.

PMID- 12045255
TI  - Pivotal role of the renin/prorenin receptor in angiotensin II production and
      cellular responses to renin.
AB  - Renin is an aspartyl protease essential for the control of blood pressure and was
      long suspected to have cellular receptors. We report the expression cloning of
      the human renin receptor complementary DNA encoding a 350-amino acid protein with
      a single transmembrane domain and no homology with any known membrane protein.
      Transfected cells stably expressing the receptor showed renin- and prorenin
      specific binding. The binding of renin induced a fourfold increase of the
      catalytic efficiency of angiotensinogen conversion to angiotensin I and induced
      an intracellular signal with phosphorylation of serine and tyrosine residues
      associated to an activation of MAP kinases ERK1 and ERK2. High levels of the
      receptor mRNA are detected in the heart, brain, placenta, and lower levels in the
      kidney and liver. By confocal microscopy the receptor is localized in the
      mesangium of glomeruli and in the subendothelium of coronary and kidney artery,
      associated to smooth muscle cells and colocalized with renin. The renin receptor
      is the first described for an aspartyl protease. This discovery emphasizes the
      role of the cell surface in angiotensin II generation and opens new perspectives
      on the tissue renin-angiotensin system and on renin effects independent of
      angiotensin II.

PMID- 12045256
TI  - Hypothalamic growth hormone secretagogue receptor regulates growth hormone
      secretion, feeding, and adiposity.
AB  - Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS
      receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and
      ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an
      endogenous ligand for GHS-R, has recently been purified from rat stomach.
      Although ghrelin is also expressed in the hypothalamus, the physiological
      significance of the ghrelin/GHS-R system is still unknown. We have created
      transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the
      promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R
      protein expression in the Arc. Tg rats had lower body weight and less adipose
      tissue than did control rats. Daily food intake was reduced, and the stimulatory
      effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and
      plasma insulin-like growth factor-I levels were reduced in female Tg rats. These
      results suggest that GHS-R in the Arc is involved in the regulation of GH
      secretion, food intake, and adiposity.

PMID- 12045257
TI  - Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and
      regulates acinar-to-ductal metaplasia in exocrine pancreas.
AB  - In gastrointestinal epithelium, metaplastic conversion between predominant cell
      types is associated with an increased risk of neoplasia. However, the mechanisms
      regulating metaplastic transitions in adult epithelia are largely undefined. Here
      we show that matrix metalloproteinase-7 (MMP-7) is expressed not only in the
      majority of human pancreatic ductal adenocarcinoma specimens, but also in human
      pancreatic intraepithelial neoplasia and metaplastic duct lesions in human and
      mouse. In a mouse model of pancreatic acinar-to-ductal metaplasia, MMP-7
      progressively accumulates during the metaplastic transition, resulting in a
      concomitant increase in solubilization of Fas ligand (FasL). Under identical
      conditions, mice either deficient in MMP-7 or carrying an inactive FasL gene are
      severely inhibited in development of progressive metaplasia and acinar cell
      apoptosis. Thus, MMP-7 and FasL influence the initiation and maintenance of
      metaplastic events in pancreatic epithelium, explaining the observed link between
      metaplasia and apoptosis in pancreas and other gastrointestinal tissues.

PMID- 12045258
TI  - Thyrostimulin, a heterodimer of two new human glycoprotein hormone subunits,
      activates the thyroid-stimulating hormone receptor.
AB  - Human thyrotropin (TSH), luteotropin (LH), follitropin (FSH), and chorionic
      gonadotropin are members of the heterodimeric glycoprotein hormone family. The
      common alpha subunit forms noncovalent heterodimers with different beta subunits.
      Two novel human glycoprotein hormonelike genes, alpha2 (A2) and beta5 (B5),
      recently have been identified. Using a yeast two-hybrid assay, the two subunits
      were found as potential heterodimerization partners. Immunological analyses
      confirmed the heterodimerization of A2 and B5 in transfected cells and their
      colocalization in the anterior pituitary. Recombinant A2/B5 heterodimeric
      glycoproteins, purified using cation exchange and size fractionation
      chromatography, activated human TSH receptors, but not LH and FSH receptors, and
      showed high affinity to TSH receptors in a radioligand receptor assay. The
      heterodimer also stimulated cAMP production and thymidine incorporation by
      cultured thyroid cells and increased serum thyroxine levels in TSH-suppressed
      rats in vivo. This new heterodimeric glycoprotein hormone was named as
      thyrostimulin based on its thyroid-stimulating activity. The expression of
      thyrostimulin in the anterior pituitary known to express TSH receptors suggested
      a paracrine mechanism. The present discovery of a new ligand based on genomic
      approaches could facilitate the understanding of the physiological roles of extra
      thyroid TSH receptor systems and the structural-functional basis of receptor
      signaling by related glycoprotein hormones.

PMID- 12045259
TI  - CD19-dependent B lymphocyte signaling thresholds influence skin fibrosis and
      autoimmunity in the tight-skin mouse.
AB  - The tight-skin (TSK/+) mouse, a genetic model for human systemic sclerosis (SSc),
      develops cutaneous fibrosis and autoantibodies against SSc-specific target
      autoantigens. Although molecular mechanisms explaining the development of
      fibrosis and autoimmunity in SSc patients or TSK/+ mice remain unknown, we
      recently demonstrated that SSc patients overexpress CD19, an important regulatory
      molecule expressed by B lymphocytes. B cells from CD19-deficient mice are
      hyporesponsive to transmembrane signals, while B cells overexpressing CD19 are
      hyperresponsive and generate autoantibodies. In this study, TSK/+ B cells also
      exhibited a hyperresponsive phenotype with decreased surface IgM expression,
      enhanced serum Ig production, and spontaneous autoantibody production. Moreover,
      CD19 tyrosine phosphorylation was constitutively augmented in TSK/+ B cells. CD19
      mediated [Ca(2+)](i) responses, Vav phosphorylation, and Lyn kinase activity were
      similarly enhanced. Studies of TSK/+ mice deficient in CD19 expression
      demonstrated that CD19 deficiency significantly decreased skin fibrosis in TSK/+
      mice. Additionally, CD19 loss in TSK/+ mice upregulated surface IgM expression
      and completely abrogated hyper-gamma-globulinemia and autoantibody production.
      CD19 deficiency also inhibited IL-6 production by TSK/+ B cells. Thus, chronic B
      cell activation resulting from augmented CD19 signaling in TSK/+ mice leads to
      skin sclerosis possibly through IL-6 overproduction as well as autoimmunity.

PMID- 12045260
TI  - Induction of CD4(+) T cell-dependent antitumor immunity by TAT-mediated tumor
      antigen delivery into dendritic cells.
AB  - Dendritic cell-based (DC-based) immunotherapy represents a promising approach to
      the prevention and treatment of many diseases, including cancer, but current
      strategies have met with only limited success in clinical and preclinical
      studies. Previous studies have demonstrated that a TAT peptide derived from the
      HIV TAT protein has the ability to transduce peptides or proteins into various
      cells. Here, we describe the use of TAT-mediated delivery of T cell peptides into
      DCs to prolong antigen presentation and enhance T cell responses. While
      immunization of mice with DCs pulsed with an antigenic peptide derived from the
      human TRP2 protein generated partial protective immunity against B16 tumor,
      immunization with DCs loaded with a TAT-TRP2 peptide resulted in complete
      protective immunity, as well as significant inhibition of lung metastases in a 3
      day tumor model. Although both DC/TRP2 and DC/TAT-TRP2 immunization increased the
      number of TRP2-specific CD8(+) T cells detected by K(b)/TRP2 tetramers, T cell
      activity elicited by DC/TAT-TRP2 was three- to tenfold higher than that induced
      by DC/TRP2. Furthermore, both CD4(+) and CD8(+) T cells were required for
      antitumor immunity demonstrated by experiments with antibody depletion of subsets
      of T cells, as well as with various knockout mice. These results suggest that a
      TAT-mediated antigen delivery system may have important clinical applications for
      cancer therapy.

PMID- 12045261
TI  - Th1 cytokines, programmed cell death, and alloreactive T cell clone size in
      transplant tolerance.
AB  - The Th1 cytokines IL-2 and IFN-gamma, which inhibit T cell proliferation and
      promote activation induced cell death, may be required to diminish alloreactive T
      cell numbers and to foster tolerance across full allogeneic barriers. However, we
      hypothesized that these cytokines might be dispensable when the alloreactive T
      cell clone size is relatively small, as is seen in recipients of minor-mismatched
      grafts. We show that alloreactive T cell clone size of C57BL/6 mice against
      multiple minor-mismatched 129X1/sv mice was approximately 4-9-fold smaller than
      that against MHC-mismatched BALB/c mice. In the MHC-mismatched combination, CD28
      B7 blockade by CTLA4Ig induced long-term graft survival in wild-type recipients,
      but this treatment was ineffective in IFNgamma(-/-) or IL-2(-/-) recipients. In
      contrast, in the minor-mismatched combination, CTLA4Ig induced long-term
      allograft survival in wild-type, IFNgamma(-/-), and IL-2(-/-) recipients. Bcl
      x(L) transgenic animals, which are defective in "passive" T cell death, are
      likewise sensitive to the effects of CTLA4Ig only in the setting of the minor
      mismatch grafts. Therefore, the alloreactive T cell clone size is an important
      determinant affecting the need for Th1 cytokines and T cell death in tolerance
      induction. These data have implications for the design of tolerance strategies in
      transplant recipients with varying degrees of MHC mismatching.

PMID- 12045262
TI  - p53 negatively regulates intestinal immunity by delaying mucosal T cell cycling.
AB  - To mount an effective immune response, T cells must divide in response to antigen
      contact. To maintain tolerance, mucosal lamina propria T cells (LPTs) may adapt
      their cycling to an antigen-rich gut stimulatory environment. Here, we compared
      the cell cycle kinetics of LPTs and peripheral blood T cells (PBTs) before and
      after CD3- and CD2-mediated activation. While CD3-activated naive (CD45RA(+)) and
      memory (CD45RO(+)) PBTs peaked in the S and G2/M phase at 2-3 days, CD3-activated
      LPTs peaked at 4-6 days. In contrast, CD2 activation induced modest PBT but
      vigorous LPT cycling. The doubling time of CD3-activated PBTs was 1 day, while
      that of CD3- or CD2-activated LPTs was 2 days. LPTs failed to upregulate cyclin
      dependent kinase 4 and cyclin D3, but Rb phosphorylation and cyclin A and B1
      upregulation were induced by CD2 engagement. The extents of clonal expansion in
      LPT and PBT were comparable, indicating that LPTs' slow replication delays but
      does not hinder cell division. CD2-activated LPTs displayed a striking
      upregulation of p53, whose blockade by antisense oligonucleotides accelerated
      their S phase transit time to that of CD3-activated PBTs. By slowing LPT cycling,
      p53 may act as a negative regulator of mucosal immunity, promoting immunological
      tolerance by preventing excessive T cell replication.

PMID- 12045263
TI  - Cytosolic phospholipase A(2) in hypoxic pulmonary vasoconstriction.
AB  - Cytosolic phospholipase A(2) (cPLA(2)) releases arachidonic acid (AA) from
      phospholipids in cell membranes. To assess the role of cPLA(2) in hypoxic
      pulmonary vasoconstriction (HPV), we measured the increase in left lung pulmonary
      vascular resistance (LPVR) before and during hypoxia produced by left main stem
      bronchus occlusion (LMBO) in mice with and without a targeted deletion of the
      PLA2g4a gene that encodes cPLA(2alpha). LMBO increased LPVR in cPLA(2alpha)(+/+)
      mice but not in cPLA(2alpha)(-/-) mice. cPLA(2alpha)(+/+) mice were better able
      to maintain systemic oxygenation during LMBO than were cPLA(2alpha)(-/-) mice.
      Administration of a cPLA(2) inhibitor, arachidonyl trifluoromethyl ketone,
      blocked the LMBO-induced increase in LPVR in wild-type mice, while exogenous AA
      restored HPV in cPLA(2alpha)(-/-) mice. Intravenous angiotensin II infusion
      increased PVR similarly in cPLA(2alpha)(+/+) and cPLA(2alpha)(-/-) mice.
      Inhibitors of cyclooxygenase or nitric oxide synthase restored HPV in
      cPLA(2alpha)(-/-) mice. Breathing 10% oxygen for 3 weeks produced less right
      ventricular hypertrophy in cPLA(2alpha)(-/-) than in cPLA(2alpha)(+/+) mice, but
      restored HPV in cPLA(2alpha)(-/-) mice despite the continued absence of cPLA(2)
      activity. These results indicate that cPLA(2) contributes to the murine pulmonary
      vasoconstrictor response to hypoxia. Augmenting pulmonary vascular tone restores
      HPV in the absence of cPLA(2) activity.

PMID- 12045265
TI  - Plant cell signal transduction: the emerging phenotype.

PMID- 12045264
TI  - Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO
      mutations.
AB  - NF-kappaB essential modifier (NEMO), also known as IKK-gamma, is a member of the
      I-kappaB kinase complex responsible for phosphorylating I-kappaB, allowing the
      release and activation of NF-kappaB. Boys with an expressed NEMO mutation have an
      X-linked syndrome characterized by hypohidrotic ectodermal dysplasia with immune
      deficiency (HED-ID). The immunophenotype resulting from NEMO mutation is highly
      variable, with deficits in both T and B cell responses. We evaluated three
      patients with NEMO mutations (L153R, Q403X, and C417R) and HED-ID who had
      evidence of defective CD40 signaling. All three patients had normal percentages
      of peripheral blood NK cells, but impaired NK cell cytotoxic activity. This was
      not due to a generalized defect in cytotoxicity because antibody-dependent
      cellular cytotoxicity was intact. This abnormality was partially reversed by in
      vitro addition of IL-2, which was also able to induce NF-kappaB activation. In
      one patient with recurrent cytomegalovirus infections, administration of IL-2
      partially corrected the NK cell killing deficit. These data suggest that NEMO
      participates in signaling pathways leading to NK cell cytotoxicity and that IL-2
      can activate NF-kappaB and partially overcome the NK cell defect in patients with
      NEMO mutations.

PMID- 12045266
TI  - A breakdown in defense signaling.

PMID- 12045267
TI  - Specificity and cross-talk in plant signal transduction: January 2002 Keystone
      Symposium.

PMID- 12045269
TI  - Cytokinin signaling in Arabidopsis.

PMID- 12045271
TI  - Ubiquitination and auxin signaling: a degrading story.

PMID- 12045270
TI  - Gibberellin signaling: biosynthesis, catabolism, and response pathways.

PMID- 12045268
TI  - Abscisic acid signaling in seeds and seedlings.

PMID- 12045272
TI  - Brassinosteroids and plant steroid hormone signaling.

PMID- 12045273
TI  - Control of flowering time: interacting pathways as a basis for diversity.

PMID- 12045274
TI  - Ethylene biosynthesis and signaling networks.

PMID- 12045275
TI  - The jasmonate signal pathway.

PMID- 12045276
TI  - Cell signaling during cold, drought, and salt stress.

PMID- 12045279
TI  - Self-incompatibility in the Brassicaceae: receptor-ligand signaling and cell-to
      cell communication.

PMID- 12045278
TI  - Blue light receptors and signal transduction.

PMID- 12045280
TI  - Rhizobium nod factor perception and signalling.

PMID- 12045281
TI  - Polypeptide hormones.

PMID- 12045282
TI  - Signaling in and out: control of cell division and differentiation in the shoot
      and root.

PMID- 12045277
TI  - Sugar sensing and signaling in plants.

PMID- 12045283
TI  - Signalling in plant lateral organ development.

PMID- 12045284
TI  - RNA silencing and the mobile silencing signal.

PMID- 12045285
TI  - Plasmodesmata: pathways for protein and ribonucleoprotein signaling.

PMID- 12045286
TI  - Signal transduction between the chloroplast and the nucleus.

PMID- 12045287
TI  - Consummating signal transduction: the role of 14-3-3 proteins in the completion
      of signal-induced transitions in protein activity.

PMID- 12045289
TI  - Small GTPases: versatile signaling switches in plants.

PMID- 12045288
TI  - Heterotrimeric and unconventional GTP binding proteins in plant cell signaling.

PMID- 12045290
TI  - Calmodulins and calcineurin B-like proteins: calcium sensors for specific signal
      response coupling in plants.

PMID- 12045292
TI  - Getting to the heart of the matter: focus on "microarray analysis of global
      changes in gene expression during cardiac myocyte differentiation".

PMID- 12045291
TI  - Calcium at the crossroads of signaling.

PMID- 12045293
TI  - Meeting report: Physiological Genomics of Cardiovascular Disease: from Technology
      to Physiology.

PMID- 12045294
TI  - Time-dependent changes in ARE-driven gene expression by use of a noise-filtering
      process for microarray data.
AB  - The current study was designed to identify the time-dependent gene expression
      profiles of antioxidant responsive element (ARE)-driven genes induced by tert
      butylhydroquinone (tBHQ). A set of simple noise-filtering methods was introduced
      to evaluate and minimize the variance of microarray datasets. Gene expression
      induced by tBHQ (10 microM) in IMR-32 human neuroblastoma cells was analyzed by
      means of large-scale oligonucleotide microarray. Rank analysis was used to
      determine the acceptable number of independent samples necessary to eliminate
      false positives from the dataset. A dramatic reduction in the number of genes
      passing the rank analysis was achieved by using a 3 x 3 matrix comparison.
      Reproducibility was evaluated based on the coefficient of variation for average
      difference change. Completion of these analyses revealed that 101 of the 9,670
      genes examined showed dynamic changes with treatment ranging from 4 h to 48 h.
      Since certain ARE-driven genes have been already identified, gene clustering
      would presumably group them together based on similar regulation. Self-organizing
      map grouped the genes induced by tBHQ into 12 (4x3) distinct clusters. Those
      previously identified ARE-driven genes were shown to group into different
      clusters. Since all potential ARE-driven genes did not cluster together, we
      speculate that multiple transcription factors and/or multiple signal transduction
      pathways contribute to transcriptional activation of the ARE. In conclusion, many
      novel potential ARE-driven genes were identified in this study. They function in
      detoxification and antioxidant defense, neuronal proliferation and
      differentiation, and signal transduction. The noise-filtering process applied to
      these microarray data, therefore, has proven to be very useful in identification
      of the time-dependent changes in ARE-drive gene expression.

PMID- 12045295
TI  - Microarray analysis of global changes in gene expression during cardiac myocyte
      differentiation.
AB  - Significant progress has been made in defining pathways that mediate the
      formation of the mammalian heart. Little is known, however, about the genetic
      program that directs the differentiation of cardiac myocytes from their precursor
      cells. A major hindrance to this kind of investigation has been the absence of an
      appropriate cell culture model of cardiac myocyte differentiation. Recently, a
      subline of P19 cells (P19CL6) was derived that, following dimethyl sulfoxide
      (DMSO) treatment, differentiate efficiently over 10 days into spontaneously
      beating cardiac myocytes. We demonstrate that these cells are indeed cardiac
      myocytes as they express cell type-specific markers and exhibit
      electrophysiological properties indicative of cardiac myocytes. The requirement
      for DMSO stimulation in this paradigm was shown to be limited to the first 4
      days, suggesting that critical events in the differentiation process occur over
      this interval. To uncover relationships among known genes and identify novel
      genes that mediate cardiac myocyte differentiation, a detailed time course of
      changes in global gene expression was carried out using cDNA microarrays. In
      addition to the activation of genes encoding cardiac transcription factors and
      structural proteins, increases were noted in the expression of multiple known
      genes and expressed sequence tags (ESTs). Analysis of the former suggested the
      involvement of a variety of signaling pathways in cardiac myocyte
      differentiation. The 16 ESTs whose expression was increased during the early,
      stimulus-dependent phase of cardiac myocyte differentiation may be novel
      regulators of this process. Thus this first report of large-scale changes in gene
      expression during cardiac myocyte differentiation has delineated relationships
      among the expression patterns of known genes and identified a number of novel
      genes that merit further study.

PMID- 12045296
TI  - Complexity and species variation of the kidney-type glutaminase gene.
AB  - Increased expression of rat kidney-type glutaminase (KGA) during metabolic
      acidosis results from selective mRNA stabilization. This process is mediated by
      an 8-base AU-sequence that functions as a pH-response element (pHRE). LLC-PK1
      FBPase+ cells, a pH-responsive porcine kidney cell line, express four distinct GA
      mRNAs. RNase H mapping indicated that three of the GA mRNAs are generated by use
      of alternative polyadenylation sites and are homologs of the rat KGA mRNA, while
      the fourth contains a different COOH-terminal coding and 3'-untranslated
      sequence. PCR cloning and sequencing established that the latter GA mRNA is the
      homolog of the human GAC mRNA. A rat GAC cDNA was also cloned from a rat kidney
      library. The 3'-untranslated regions of the GAC mRNAs, but not the porcine or
      human KGA mRNAs, contain identifiable pHREs. The human KGA gene spans 82 kb and
      is composed of 19 exons. The unique sequence from the hGAC cDNA is contained in a
      single exon. Thus in humans, alternative splicing of the initial transcript could
      produce two GA mRNAs, only one of which may be increased during acidosis.

PMID- 12045297
TI  - Proteinuria and glomerulosclerosis in the Sabra genetic rat model of salt
      susceptibility.
AB  - In search of an experimental model that would simulate the association between
      proteinuria and salt sensitivity in humans, we studied protein excretion in the
      Sabra rat model of salt susceptibility. Monthly measurements of urinary protein
      excretion in animals fed standard rat chow revealed that normotensive salt
      sensitive SBH/y developed proteinuria that averaged 65 +/- 7 mg/day (n = 10) at 9
      mo, whereas proteinuria in normotensive salt-resistant SBN/y was 39 +/- 4 mg/day
      (n = 10) (P < 0.01). Histopathological evaluation revealed focal and segmental
      glomerulosclerosis (FSGS) lesions grade 2 in SBH/y and normal histology in SBN/y.
      To amplify the differences between the strains, uninephrectomy was performed. At
      9 mo, proteinuria in SBH/y with one kidney (SBH/y-1K) was 195 +/- 12 mg/day (n =
      10) and in SBN/y was 128 +/- 10 mg/day (n = 10) (P < 0.001); histopathology
      revealed FSGS grade 3 in SBH/y-1K and grade 1-2 in SBN/y-1K. To determine the
      effect of salt loading, animals were provided with 8% NaCl in chow, causing
      hypertension in SBH/y but not in SBN/y. Proteinuria markedly increased in both
      SBH/y with two kidneys (SBH/y-2K) and SBH/y-1K, but not in SBN/y; histopathology
      revealed FSGS grade 1-2 in SBH/y-2K, grade 2 in SBH/y-1K, no lesions in SBN/y-2K,
      and grade 0-1 in SBN/y-1K. We concluded that the SBH/y strain is more susceptible
      to develop proteinuria and glomerulosclerosis than SBN/y. In search for the
      genetic basis of this phenomenon, we investigated the role of candidate
      proteinuric gene loci. Consomic strains were constructed by introgressing
      chromosome 1 (which harbors the rf-1 and rf-2 proteinuric loci) or chromosome 17
      (which harbors rf-5) from SBH/y onto the SBN/y genomic background. The resulting
      consomic strains developed marked proteinuria that was severalfold higher than in
      SBN/y-1K; histopathological evaluation, however, revealed FSGS lesions grade 1-2,
      similar to those found in SBN/y-1K and less severe than in SBH/y-1K. These
      results suggest a functional role of gene systems located on chromosomes 1 and 17
      in inducing proteinuria in the salt-susceptible Sabra rat strain. These genetic
      loci do not appear to harbor major genes for glomerulosclerosis.

PMID- 12045298
TI  - Patient care and the information explosion.

PMID- 12045300
TI  - Self-restraint, self-examination: a historical perspective on restraints and
      ethics in psychiatry.

PMID- 12045301
TI  - Anatomy of the mind.

PMID- 12045302
TI  - Consumer & family information. Ecstasy.

PMID- 12045303
TI  - A web-based data management system to improve care for depression in a
      multicenter clinical trial.

PMID- 12045304
TI  - Variations in mental health specialty care across metropolitan areas.

PMID- 12045305
TI  - The optimum expenditure for state hospitals and its relationship to the suicide
      rate.

PMID- 12045306
TI  - Psychiatric management of Huntington's disease in extended care settings.

PMID- 12045307
TI  - Responsibility and choice in addiction.
AB  - The treatment of patients with substance use disorders requires that providers be
      aware of their own views on the relative roles of personal responsibility and of
      forces outside personal control in the onset and progression of and recovery from
      these disorders. The authors review the role of responsibility for addiction from
      several viewpoints: biological, psychological, sociocultural, self-help,
      religious, and forensic. Factors that affect personal responsibility in addictive
      diseases include awareness of the problem, knowledge of a genetic predisposition,
      understanding of addictive processes, comorbid psychiatric or medical conditions,
      adequacy of the support network, nature of the early environment, degree of
      tolerance of substance abuse in the sociocultural context, and the availability
      of competent psychiatric, medical, and chemical dependency treatment. Factors
      that affect societal responsibility include degree of access to illicit drugs,
      society's level of tolerance of drug use, the courts' approach to deterring
      substance abuse (punishment versus treatment), individuals' refusal to obtain
      substance abuse treatment, presence of clear behavioral norms, availability of
      early assessment and prevention, presence of community education, and degree of
      access to outpatient and community treatment.

PMID- 12045308
TI  - Quality of life in social anxiety disorder compared with panic disorder and the
      general population.
AB  - OBJECTIVE: Quality of life in a treatment-seeking cohort of patients with social
      anxiety disorder was compared with that of patients with panic disorder who were
      matched for age, comorbid illnesses, and gender and with population-based norms.
      METHODS: The study participants were 33 patients with social anxiety disorder and
      33 patients with panic disorder who had participated in clinical trials and who
      had completed the Medical Outcomes Study Short-Form-36 (SF-36) as part of a
      baseline evaluation. The patients did not have significant comorbid psychiatric
      disorders. Paired t tests were used to compare baseline scores on subscales of
      the SF-36 between the two cohorts. One-sample t tests were used to compare scores
      on subscales of the SF-36 with expectation scores based on 2,474 persons from the
      general population. RESULTS: Compared with the general population, the patients
      with social anxiety disorder had significantly greater impairment as measured by
      the SF-36 social functioning and mental health subscales. Subscale scores also
      indicated poorer emotional role functioning, but the difference was not
      significant. However, they were significantly less impaired than the patients
      with panic disorder in terms of physical functioning, physical role, and mental
      health. CONCLUSIONS: Patients with social anxiety disorder who do not have
      significant comorbid depression or anxiety are substantially impaired in quality
      of life, but to a lesser extent than patients with panic disorder, who suffer
      from both mental and physical impairments in quality of life.

PMID- 12045309
TI  - Psychotic ideation and receipt of government entitlements among homeless persons
      in New York City.
AB  - OBJECTIVE: This study compared changes in receipt of government entitlements by
      homeless persons with and without psychotic ideation in New York City between
      January 1997 and July 1998, a period characterized by changing state government
      policies and greater bureaucratic monitoring of eligibility. METHODS: In
      conjunction with an experimental study of the efficacy of social work services
      provided to homeless persons in Manhattan by a mobile medical van, 25 persons who
      were assessed as having experienced psychotic ideation in the previous year and
      134 nonpsychotic persons were followed up after four months to identify changes
      in their receipt of Medicaid benefits, Supplemental Security Income (SSI) or
      Social Security Disability Insurance (SSDI), food stamps, and home relief (state
      welfare for single persons). The social work intervention was designed to help
      eligible clients gain access to entitlements and substance abuse treatment.
      RESULTS: The proportion of clients with psychotic ideation who received Medicaid,
      food stamps, or home relief decreased during the study period, while the
      proportion of nonpsychotic clients who received these entitlements increased.
      Little change was observed in receipt of SSI or SSDI by either group.
      CONCLUSIONS: Psychotic ideation among homeless persons may be a significant
      factor in access to and maintenance of government entitlements. In the context of
      an increasingly restrictive and bureaucratic welfare system, providing assistance
      to homeless persons who have severe psychopathology presents new challenges to
      service providers.

PMID- 12045310
TI  - Priorities of consumers, providers, and family members in the treatment of
      schizophrenia.
AB  - OBJECTIVE: This study explored the extent and nature of agreement on outcome and
      service priorities between consumers, their providers, and their family members
      as well as providers' and family members' awareness of consumers' priorities.
      METHODS: Interviews were conducted with members of 60 stakeholder sets that
      included a person with schizophrenia, one of his or her mental health care
      providers, and one of his or her family members. Each member of the set ranked
      seven outcomes and nine services in order of importance and rated the relative
      importance of each. Family members and providers also ranked the outcomes and
      services in the order in which they believed the consumer would rank them.
      Magnitude-estimation-preference-weight ratios and Kendall's rank-order
      correlation were used to evaluate pairwise (consumer and provider, consumer and
      family member, and family member and provider) and within-set agreement. RESULTS:
      Pairwise and within-set agreement was low. In general, no more than a third of
      the pairs agreed on outcome priorities, and no more than half agreed on service
      priorities. In about half of the 60 sets, none of the three pairs agreed on
      outcome priorities. Awareness of consumers' priorities was limited. Family
      members' and providers' estimates of consumers' outcome priorities were more
      similar to their own preferences than to consumers'. Low rates of agreement were
      also noted for providers' estimates of consumers' service priorities. Within-set
      agreement was lower than agreement by type of stakeholder. CONCLUSIONS: Current
      goal-setting in nonresearch clinical settings is generating neither consensus nor
      a shared understanding of consumers' priorities. Priorities vary widely among
      consumers, among providers, and among family members.

PMID- 12045311
TI  - Global Assessment of Functioning ratings and the allocation and outcomes of
      mental health services.
AB  - OBJECTIVE: The Global Assessment of Functioning (GAF) is an integral part of the
      standard multiaxial psychiatric diagnostic system. The purpose of including the
      GAF in DSM-IV as a tool for axis V assessment is to enable clinicians to obtain
      information about global functioning to supplement existing data about symptoms
      and diagnoses and to help predict the allocation and outcomes of mental health
      treatment. The purpose of this study was to examine the value of the GAF as part
      of a systemwide program for monitoring the allocation and outcomes of mental
      health care services. METHODS: Clinicians used the GAF to assess global
      functioning among 9,854 patients with psychiatric or substance use disorders, or
      both, who were already participating in an outcomes monitoring program of the
      Department of Veterans Affairs. A longitudinal prospective follow-up design was
      used. RESULTS: Patients' clinical diagnoses and symptoms were stronger predictors
      of GAF ratings than was their social or occupational functioning. GAF-rated
      impairment was associated with the provision of inpatient or residential care and
      outpatient psychiatric care, but patients with greater levels of impairment did
      not receive more treatment. GAF ratings were only minimally associated with
      treatment outcomes. No robust associations were found between GAF ratings and
      outcomes as assessed by clinician interview or by patients' self-report at follow
      up. CONCLUSIONS: Including GAF ratings in a program for predicting the allocation
      and outcomes of mental health care is of questionable value. Research is needed
      to determine whether systematic training and ongoing validity checks would
      enhance the contribution of the GAF in monitoring service use and outcomes.

PMID- 12045312
TI  - Chronic suicidality among patients with borderline personality disorder.
AB  - OBJECTIVE: This paper reviews research on chronic suicidality among patients with
      borderline personality disorder. METHODS: MEDLINE and PsycINFO databases were
      searched for all English-language articles published between 1984 and 2000
      containing the keywords "borderline personality disorder" and "suicide" or
      "suicidality." A total of 170 articles located through this search and additional
      key articles published before 1990 were reviewed. The most relevant articles were
      selected of review. RESULTS AND CONCLUSIONS: One in ten patients with borderline
      personality disorder completes suicide, but this outcome is not readily
      preventable and does not necessarily occur during the course of treatment. In
      outpatient psychotherapy, chronic suicidal behavior by patients with borderline
      personality disorder can be best understood as a way of communicating distress.
      Hospitalization is of unproven value in preventing suicide by these patients and
      can sometimes have negative effects. Clinicians' fear of potential litigation
      resulting from a completed suicide should not be the basis for admission. With no
      evidence that full hospitalization prevents suicide completion by patients with
      borderline personality, suicidal risk is not a contraindication for day hospital
      treatment.

PMID- 12045313
TI  - An exploratory analysis of behavioral health care use within families.
AB  - OBJECTIVES: The authors studied enrollees in employer-sponsored managed health
      plans to determine the extent of multiple behavioral health consumers within
      families, use of behavioral health services by employees who have another family
      member using such services, congruence of diagnoses between two family members
      using behavioral health services, and the effect on covered charge per behavioral
      health consumer when other family members use behavioral health services.
      METHODS: Claims data from 911 plans sold or managed by a single managed
      behavioral health care company were examined. The plans provided coverage for
      724,789 employees and covered about 1.7 million lives. Family members of
      employees were identified by the relationship codes on the claims. Service
      utilization rates were calculated for employees overall and for employees who had
      spouses or children who used behavioral health services. Mean and median covered
      charges were determined and were examined by number and type of consumers in the
      family. RESULTS: The use of behavioral health services was greater among
      employees whose children or spouses used behavioral health services. Utilization
      rates varied by the child's or spouse's diagnoses. More than 50 percent of male
      employees whose children received treatment for a depressive disorder also
      received such treatment. Congruence of diagnoses within families was noted.
      Covered charges per person generally increased with the number of family members
      who used behavioral health services. CONCLUSION: Greater knowledge about patterns
      of use of behavioral health services within families may help in improving access
      to care and developing more effective family interventions.

PMID- 12045314
TI  - Service use among patients with schizophrenia in psychoeducational multiple
      family group treatment.
AB  - OBJECTIVES: Outpatient and inpatient mental health service outcomes for
      outpatients with schizophrenia or schizoaffective disorder who received
      psychoeducational multiple-family group treatment were compared with outcomes for
      similar patients who received standard care. METHODS: A total of 106 outpatients
      with schizophrenia or schizoaffective disorder who were receiving services from a
      large community mental health center were randomly assigned to receive standard
      care or standard care plus multiple-family group treatment. The two-year multiple
      family intervention consisted of weekly group sessions designed to educate
      patients and their family members about the biological basis of mental illness
      and treatment, to improve illness management and coping skills, and to provide
      social support. The group sessions were conducted by two clinicians using a
      standardized protocol. Each multiple-family group included five to eight families
      and consumers. Service records for the year before and after random assignment to
      the study groups were examined in an intent-to-treat analysis. RESULTS: During
      the year after random assignment to study groups, multiple-family group treatment
      was associated with a lower rate of psychiatric hospitalization than standard
      care. It was only marginally associated with lower use of crisis services, and it
      was not associated with the amount of outpatient service time. CONCLUSIONS: The
      findings suggest that implementation of multiple-family group treatment in a
      capitated community mental health setting improves hospitalization outcomes
      without increasing the overall volume of outpatient mental health services.

PMID- 12045316
TI  - Screening for alcohol abuse among urban Native Americans in a primary care
      setting.
AB  - The authors examined the rate of and factors associated with alcohol abuse among
      754 urban American Indian and Alaska Native primary care patients. Data were
      collected through a self-administered survey and by abstracting medical records.
      A total of 423 respondents (56 percent) screened positive for lifetime alcohol
      abuse, and 202 (27 percent) reported current alcohol abuse. A diagnosis of
      alcohol abuse was found in the medical records of 68 of the patients who screened
      positive (16 percent). Logistic regression analysis showed that being male,
      having been a victim of violence, and feeling depressed were associated with
      alcohol abuse. Further research is warranted to help clinicians detect and treat
      alcohol abuse in this special population.

PMID- 12045315
TI  - Efficacy of olanzapine and risperidone for treatment-refractory schizophrenia
      among long-stay state hospital patients.
AB  - The authors studied the efficacy of olanzapine and risperidone among patients
      with treatment-refractory schizophrenia who had been hospitalized for more than
      five years and who were not suitable candidates for a clozapine trial. The
      patients were systematically reassessed and were given olanzapine or risperidone
      as part of a "second-chance program." The patients in both groups showed
      significant improvement in scores on the 18-item Brief Psychiatric Rating Scale
      after three months. Forty-four percent of the patients in the olanzapine group
      and 43 percent of those in the risperidone group were discharged to supervised
      residences on the basis of their clinical improvement. There is value in
      reassessing long-stay patients who have treatment-refractory schizophrenia and
      giving them systematic trials with new medications that become available.

PMID- 12045317
TI  - An exploratory study of what clients like least about assertive community
      treatment.
AB  - As part of a larger interview, clients of assertive community treatment programs
      answered an open-ended question about what they liked least about assertive
      community treatment. Of 182 clients, 44 percent reported that they disliked
      nothing; 21 percent said that they disliked features that are considered specific
      to assertive community treatment, such as home visits, or that have been
      criticized in the literature, such as intrusiveness; 16 percent said that they
      were dissatisfied with underimplementation of elements thought to characterize
      assertive community treatment, such as frequency of visits; and 19 percent said
      that they were dissatisfied with general aspects of mental health service
      delivery, such as an inconvenient office location. Compared with clients of
      programs with low levels of fidelity to assertive community treatment, clients of
      high-fidelity programs had fewer complaints overall and fewer complaints about
      features considered to be specific to assertive community treatment.

PMID- 12045318
TI  - Use of case manager ratings and weekly urine toxicology tests among outpatients
      with dual diagnoses.
AB  - Use of drugs and alcohol by 43 predominantly male outpatients who had severe
      mental illness and a comorbid substance use disorder were assessed weekly through
      the ratings of experienced dual disorder case managers and through blinded
      research urine toxicology tests. The percentage of weeks in which drugs or
      alcohol were used was calculated on the basis of one or both assessments. The
      case managers often missed drug use over the weekends, which was detected by the
      urine toxicology tests. Agreement between the two methods varied widely, even
      when the ratings were made by highly experienced case managers. These findings
      have implications for monitoring patients with dual diagnoses and provide insight
      into the accuracy of case manager ratings.

PMID- 12045319
TI  - Occupational theraphy and the multidisciplinary team.

PMID- 12045320
TI  - Occupational therapy and the multidisciplinary team.

PMID- 12045322
TI  - Reexamining therapist self-disclosure.

PMID- 12045324
TI  - Total synthesis and biosynthesis of the paraherquamides: an intriguing story of
      the biological Diels-Alder construction.
AB  - The syntheses and biosyntheses of the paraherquamide and brevianamide families of
      prenylated indole-derived alkaloids are reviewed. It has been proposed that the
      unique bicyclo[2.2.2]diazaoctan ring system that is common to this family of
      natural products, arises by a biological intramolecular Diels-Alder cycloaddition
      reaction. Both synthetic approaches and total syntheses of several members of
      this family of natural products are reviewed. The biosynthesis of these alkaloids
      has also constituted an active area of research and the current state of
      knowledge on the biosynthesis of these natural products are reviewed.

PMID- 12045325
TI  - Dissolution tests for self-setting calcium phosphate cement-containing
      nifedipine.
AB  - Nifedipine-containing calcium phosphate cement (CPC) was prepared, and nifedipine
      (NF) release from this preparation was evaluated by the shaking method (SK),
      Japanese Pharmacopoeia XIV (JPXIV) paddle method (PD), and JPXIV flow-through
      cell method (FT). The release of NF from the CPC preparation continued for 7 d or
      longer by all these methods. This suggests that the release of NF can be
      controlled by preparing NF-containing CPC. The release pattern of NF from CPC in
      these tests was found to follow the Higuchi equation. However, the Higuchi
      constant differed among the three dissolution tests, probably because the
      apparent tortuosity of capillary system (tau) varied.

PMID- 12045326
TI  - Improvement of a biomimetic porphyrin catalytic system by addition of acids.
AB  - The conditions of the use of the manganese/porphyrin/imidazole system needed to
      be improved in order to obtain larger amounts of models of metabolites. An
      increase of the oxidation yields and a better preservation of this catalytic
      system have been obtained on the examples of various alkanes, by an acid addition
      in the reaction mixture. Three manganoporphyrins were checked for evaluation of
      the reaction. These results were extended to molecules of therapeutical interest
      such as ibuprofen and phenylbutazone.

PMID- 12045327
TI  - Phospholipid deformable vesicles for buccal delivery of insulin.
AB  - To investigate the possibility of the enhancing effect of deformable vesicles on
      buccal delivery of insulin, two kinds of vesicles with and without the presence
      of sodium deoxycholate (deformable vesicles and conventional vesicles) were
      prepared by reverse phase evaporation methods. The liposomal entrapment
      efficiency was determined by column chromatography. The particle size and
      morphology of the vesicles were also evaluated. The hypoglycemic effects, insulin
      concentrations, and residual amounts of insulin deposited in the buccal membrane
      after buccal administration of insulin vesicles to rabbits were investigated.
      Compared with subcutaneous administration of insulin solution, the relative
      pharmacological bioavailability and the relative bioavailability of buccal
      administration of insulin vesicles were determined. The results showed that the
      entrapment efficiencies of the deformable and conventional vesicles were 18.87+/
      1.78% (n=3) and 22.07+/-2.16% (n=3), respectively. The particle sizes of the
      deformable and conventional vesicles were 42.5+/-20.5 nm and 59.7+/-33.8 nm,
      respectively. There were no significant differences in appearance between the two
      types of vesicle. Compared with subcutaneous administration of insulin solution,
      the relative pharmacological bioavailability and the relative bioavailability in
      the insulin-deformable vesicles group were 15.59% and 19.78%, respectively, which
      were higher than in the conventional insulin vesicles (p<0.05), blank deformable
      vesicles and insulin mixture groups (p<0.05). Deformable vesicles have an
      enhancing effect on buccal delivery of insulin and may be a better carrier than
      conventional vesicles for buccal delivery of protein drugs.

PMID- 12045328
TI  - Synthesis and cytotoxic activities of pyrrole[2,3-d]pyridazin-4-one derivatives.
AB  - 1-Methyl-2-phenyl (1) and 1,3-dimethyl-2-phenyl (2)-substituted pyrrole[2,3
      d]pyridazinones, as well as their tetracyclic analogues 3-6, were synthesized and
      evaluated in vitro by the National Cancer Institute against 60 human tumor cell
      lines derived from nine cancer cell types. Biological results showed that the
      antitumor activities of these compounds were related to the planarity of their
      ring systems with potency increasing in the order 2<4 congruent with 5<6<3. Among
      them, the most potent compound 3 showed significant cell line cytotoxicity,
      particularly against the renal cancer subpanel [GI(50) (microM) 5.07] and
      displayed significant potency [GI(50) (microM) 3.04-4.32] against MOLT-4, SR
      (leukemia), NCI-H460 (non-small cell lung), HCT-116 (colon), and SF-295 (CNS)
      cancer cells, respectively.

PMID- 12045329
TI  - Withanolide derivatives from the roots of Withania somnifera and their neurite
      outgrowth activities.
AB  - Five new withanolide derivatives (1, 9-12) were isolated from the roots of
      Withania somnifera together with fourteen known compounds (2-8, 13-19). On the
      basis of spectroscopic and physiochemical evidence, compounds 1 and 9-12 were
      determined to be (20S,22R)-3 alpha,6 alpha-epoxy-4 beta,5 beta,27-trihydroxy-1
      oxowitha-24-enolide (1), 27-O-beta-D-glucopyranosylpubesenolide 3-O-beta-D
      glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside VIII, 9), 27-O-beta-D
      glucopyranosyl (1-->6)-beta-D-glucopyranosylpubesenolide 3-O-beta-D
      glucopyranosyl (1-->6)-beta-D-glucopyranoside (withanoside IX, 10), 27-O-beta-D
      glucopyranosylpubesenolide 3-O-beta-D-glucopyranoside (withanoside X, 11), and
      (20R,22R)-1 alpha,3 beta,20,27-tetrahydroxywitha-5,24-dienolide 3-O-beta-D
      glucopyranoside (withanoside XI, 12). Of the isolated compounds, 1, withanolide A
      (2), (20S,22R)-4 beta,5 beta,6 alpha,27-tetrahydroxy-1-oxowitha-2,24-dienolide
      (6), withanoside IV (14), withanoside VI (15) and coagulin Q (16) showed
      significant neurite outgrowth activity at a concentration of 1 microM on a human
      neuroblastoma SH-SY5Y cell line.

PMID- 12045330
TI  - Effect of water content on the solid-state stability in two isomorphic clathrates
      of cephalosporin: cefazolin sodium pentahydrate (alpha form) and FK041 hydrate.
AB  - This study clearly demonstrates that clathrated water molecules can contribute to
      both chemical stabilization and destabilization of clathrates. The solid-state
      stabilities for two isomorphic clathrates of cephalosporin, cefazolin sodium and
      FK041, were investigated in terms of the effects of water content. The isomorphic
      ranges of water content were estimated to be 3.5-5 mol/mol for alpha-form
      cefazolin sodium and 2-4 mol/mol for FK041 hydrate. Upon the isomorphic
      dehydration, alpha-form cefazolin sodium was destabilized as the water content
      decreased below 4.25 mol/mol owing to the disruption of hydrogen bonding network
      in lattice channels. In this case, the hydration of clathrated water up to 4.25
      mol/mol contributed to the physical and chemical stability of the crystals. On
      the contrary, the isomorphic hydration in FK041 hydrate contributed to the
      chemical destabilization owing to the high water activity. The difference in
      water activity between alpha-form cefazolin sodium and FK041 hydrate could be
      attributed to the size of water channels.

PMID- 12045331
TI  - Structure-activity relationships (SAR) of [D-Arg(2)]dermorphin(1-4) analogues,
      N(alpha)-amidino-Tyr-D-Arg-Phe-X.
AB  - In investigating the development of compounds with potent analgesic effects after
      oral administration, 74 C-terminal analogues (N(alpha)-amidino-Tyr-D-Arg-Phe-X),
      based on the structure of N(alpha)-amidino-Tyr-D-Arg-Phe-Me beta Ala-OH (ADAMB),
      were synthesized. Their analgesic activity was evaluated using the mouse-tail
      pressure test after both subcutaneous and oral administration, and the structure
      activity relationships (SAR) were examined in detail. The results clearly
      indicated that compounds containing beta-amino acid without a side chain at the X
      position are preferable for expression of potent analgesic activity, and that the
      free carboxyl group is superior in its analgesic activity to that of the
      esterified or amidated carboxy group at the C-terminal. In addition, N
      methylation of the amide bond at the 4th position contributed to improved
      analgesic activity. These results indicated that the strong and long-lasting
      analgesic effect of ADAMB is expressed by the synergistic effects of N(alpha)
      amidination, the N-methylation of the amide bond at the 4th position and the
      carbon chain length (beta-Ala) of the residue at the 4th position, and that this
      is the most suitable structure.

PMID- 12045333
TI  - Structural requirements of flavonoids and related compounds for aldose reductase
      inhibitory activity.
AB  - The methanolic extracts of several natural medicines and medicinal foodstuffs
      were found to show an inhibitory effect on rat lens aldose reductase. In most
      cases, flavonoids were isolated as the active constituents by bioassay-guided
      separation, and among them, quercitrin (IC(50)=0.15 microM), guaijaverin (0.18
      microM), and desmanthin-1 (0.082 microM) exhibited potent inhibitory activity.
      Desmanthin-1 showed the most potent activity, which was equivalent to that of a
      commercial synthetic aldose reductase inhibitor, epalrestat (0.072 microM). In
      order to clarify the structural requirements of flavonoids for aldose reductase
      inhibitory activity, various flavonoids and related compounds were examined. The
      results suggested the following structural requirements of flavonoid: 1) the
      flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring
      (the 3',4'-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl
      moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties
      reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the
      flavones and flavonols having the catechol moiety at the B ring exhibit stronger
      activity than those having the pyrogallol moiety (the 3',4',5'-trihydroxyl
      moiety).

PMID- 12045332
TI  - New taxane diterpenoids from the roots of Taiwanese Taxus mairei.
AB  - Five new taxane diterpenoids, taxumairols G (1), H (2), I (3), J (4), and L (5)
      were isolated from extracts of the roots of Taiwanese Taxus mairei (LEMEE &
      LEVL.) S. Y. Hu. Compounds 1-4 belong to the new 11(15-->1)-abeo-taxene system,
      having a tetrahydrofuran ring along carbons C-2, C-3, C-4 and C-20. Compounds 3
      and 4 contain an isopropenyl group at C-1 while compounds 1 and 2 are attached
      with a benzoxyl group at C-15. The structures of compounds 1-5 were determined on
      the basis of two-dimensional (2D)-NMR techniques including correlation
      spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear
      multiple bond correlation (HMBC), and nuclear Overhauser effect spectroscopy
      (NOESY) experiments.

PMID- 12045334
TI  - Stilbene derivatives from two species of Gnetaceae.
AB  - Five new stilbene oligomers (gnemonols A, B and C, gnemonoside E and gnetal) were
      isolated together with 2b-hydroxyampelopsin F and gnetin E from Gnetum gnemon and
      G. gnemonoides. The structures of the compounds were elucidated on the basis of
      spectral evidence.

PMID- 12045335
TI  - Preparation of solid dispersion for ethenzamide-carbopol and theophylline
      carbopol systems using a twin screw extruder.
AB  - In the present study, we prepared solid dispersions of water-insoluble and
      soluble drugs (ethenzamide (ETZ) and theophylline (THEO)) by the twin screw
      extruder method, which made it possible to control both kneading and heating at
      the same time under the fusion point of each drug, using three types of the
      controlled-release high-molecular-weight substance Carbopol (CAR) as the carrier.
      The solid dispersions obtained were evaluated and compared with those prepared by
      the organic solvent method. These products showed significantly increased
      solubility of ETZ, but the solubility of THEO was reduced indicating that CAR
      slows the release of THEO. It is important not only to simply knead under high
      pressure but to select the optimal operation temperature to bring these drugs
      into a semi-fusion state. Solid dispersions obtained by this method showed X-ray
      diffraction and differential scanning calorimetry (DSC) patterns similar to those
      obtained by the organic solvent method indicating that the former can be used as
      a simple and effective method for preparation of solid dispersions.

PMID- 12045336
TI  - Cytotoxic and apoptosis-inducing ent-kaurane-type diterpenoids from the Japanese
      liverwort Jungermannia truncata NEES.
AB  - Five new ent-kaurane-type diterpenoids and a new gymnomitrane (=barbatane)-type
      sesquiterpenoid have been isolated from the Japanese liverwort Jungermannia
      truncata NEES, together with twelve previously known ent-kaurane-type
      diterpenoids. The structures of the new compounds were elucidated by two
      dimensional (2D) NMR experiments and chemical reaction. Some of the isolated
      compounds showed cytotoxicity against human leukemia cell lines and induced
      apoptosis.

PMID- 12045337
TI  - Release from or through a wax matrix system. III. Basic properties of release
      through the wax matrix layer.
AB  - Release property of reservoir device matrix tablet was examined. Wax matrix layer
      was prepared from physical mixture of lactose and hydrogenated castor oil to
      obtain basic release properties. Release process showed zero order kinetics in a
      steady state after a given lag times, and could be divided into two stages. The
      first stage was the formation process of water channel by dissolving the soluble
      component in the wax matrix layer. The lag time was considered to be the time
      required forming water channel and the time begun to release drug through the wax
      matrix layer at the same time. The lag time obtained by applying the square root
      law equation was well connected with the amount of matrix layer and mixed weight
      fraction of component in matrix layer. The second stage was the zero order
      release process of drug in the reservoir through the wax matrix layer. The
      release rate constants were calculated by taking into accounts of the thickness
      of matrix layer and permeability coefficient, and were well connected with the
      amount of matrix layer and mixed weight fraction of component. Also it was
      suggested that the tortuosity of matrix layer could be expressed by a function of
      the porosity defined by the mixed weight fraction.

PMID- 12045338
TI  - Y-931, a novel atypical antipsychotic drug, is less sensitive to oxidative
      phenomena.
AB  - The oxidation behavior of Y-931, a potent atypical antipsychotic drug, was
      compared with that of clozapine and olanzapine. In two enzymatic systems
      (horseradish peroxidase (HRP)/glutathione (GSH) and HRP/H(2)O(2)/GSH) which
      generate thiyl radicals, clozapine markedly strengthened the electron
      paramagnetic resonance (EPR) signal for the radical. Olanzapine, Y-931 and the
      major metabolites (compounds 1-3) had no or minimal effect on the intensity of
      this signal. In addition, the redox potential values for the three derivatives
      were in accord with the EPR spin trapping results. In toxicological experiments
      in human leukocytes, a concentration-dependent toxicity was observed when
      neutrophils were incubated with clozapine (1-10 micromol/l) and H(2)O(2) (1
      mmol/l). However, Y-931 and olanzapine did not show remarkable toxicity under the
      conditions.

PMID- 12045339
TI  - Effect of water on the molecular mobility of sucrose and poly(vinylpyrrolidone)
      in a colyophilized formulation as measured by (13)C-NMR relaxation time.
AB  - Individual molecular mobility of sucrose and poly(vinylpyrrolidone) (PVP) in a
      colyophilized mixture of 1 : 1 by weight has been determined by (13)C spin
      lattice relaxation times in the laboratory frame (T(1)) and in the rotating frame
      (T(1 rho)) for systems containing absorbed water at various levels. The T(1) of
      the PVP pyrrolidone ring carbon increased with storage relative humidity (RH) in
      lyophilized PVP alone, indicating that the MHz-order motions of PVP side chain
      increased with storage RH. However, in the colyophilized mixture, the side chain
      motions of PVP did not change with storage RH, and showed similar mobility to
      sucrose. This may be caused by hydrogen bonding between the PVP ring carbonyl
      group and hydroxyl group of sucrose, as suggested by a previous FT-Raman study.
      The mid-kHz-order motions of sucrose in the sucrose-PVP mixture as determined by
      T(1 rho) did not increase with storage RH as much as in lyophilized sucrose
      alone. This suggests that the molecular mobility of sucrose decreases in the
      presence of PVP due to hydrogen bonding between the hydroxyl group of sucrose and
      the carbonyl group of PVP. Inhibition of sucrose crystallization by PVP in the
      presence of water appears to be linked to the effect of PVP on the molecular
      mobility of sucrose.

PMID- 12045340
TI  - Lembehsterols A and B, novel sulfated sterols inhibiting thymidine phosphorylase,
      from the marine sponge Petrosia strongylata.
AB  - Lembehsterols A (1) and B (2), two novel sulfated sterols, were isolated from the
      marine sponge Petrosia strongylata. Both sterols showed inhibitory activity
      against thymidine phosphorylase, which is an enzyme related to angiogenesis in
      solid tumors. The structures of these sulfated sterols were established on the
      basis of chemical and physicochemical evidence.

PMID- 12045341
TI  - Unusual enzymatic hydrolysis of NAD by solubilized form of NAD(+) glycohydrolase.
AB  - Using solubilized form (sNADase) of membrane-bound porcine brain NAD(+)
      glycohydrolase (pNADase), the NADase-catalyzed hydrolysis and transglycosidation
      reactions of NAD (1) were examined. Unexpectedly, products in the reactions were
      found to be nicotinamide (5'-O-diphosphono)-beta-D-ribofuranoside (4) and
      adenosine (5). Adenosine 5'-diphosphate (ADP)-ribose (2) and nicotinamide (3) as
      well as a transglycosylated product, which are formed in a usual NAD/pNADase
      reaction system, were scarcely produced in the NAD/sNADase system. Setting aside
      the mechanical aspects of this unusual cleaving, it is quite interesting that the
      sNADase-catalyzed hydrolytic reaction of NAD resulted in the selective cleavage
      of the P-O bond of the adenosine side without the appreciable hydrolysis of the
      labile quaternary nicotinamide-ribose pyridinium linkage.

PMID- 12045342
TI  - A new neuroprotective pinusolide derivative from the leaves of Biota orientalis.
AB  - A new pinusolide derivative, 15-methoxypinusolidic acid (1), and another new
      isopimarane diterpene, ent-isopimara-15-en-3 alpha,8 alpha-diol (2) with three
      known diterpenes, lambertianic acid (3), isopimara-8(9),15-dien-18-oic acid (4)
      and isopimara-7(8),15-dien-3 beta,18-diol (5) were isolated from the 90% MeOH
      fraction of Biota orientalis (L.) ENDL. (Cupressaceae) leaves. Chemical
      structures of 1-5 were elucidated by analyses of their spectral data, including
      the two-dimensional (2D) NMR technique. Compound 1 showed significant protective
      activity against glutamate-induced neurotoxicity in primary cultures of rat
      cortical cells.

PMID- 12045343
TI  - New triterpene aldehydes, lucialdehydes A-C, from Ganoderma lucidum and their
      cytotoxicity against murine and human tumor cells.
AB  - Three new lanostante-type triterpene aldehydes, named lucialdehydes A-C (1-3),
      were isolated from the fruiting bodies of Ganoderma lucidum, together with
      ganodermanonol (4), ganodermadiol (5), ganodermanondiol (6), ganodermanontriol
      (7), ganoderic acid A (8), ganoderic acid B8 (9), and ganoderic acid C1 (10). The
      structures of the new triterpenes were determined as (24E)-3 beta-hydroxy-5 alpha
      lanosta-7,9(11),24-trien-26-al (1), (24E)-3,7-dioxo-5 alpha-lanosta-8,24-dien-26
      al (2), and (24E)-3 beta-hydroxy-7-oxo-5 alpha-lanosta-8,24-dien-26-al (3),
      respectively, by spectroscopic means. The cytotoxicity of the compounds isolated
      from the ganoderma mushroom was tested in vitro against Lewis lung carcinoma
      (LLC), T-47D, Sarcoma 180, and Meth-A tumor cell lines. Lucialdehydes B, C (2,
      3), ganodermanonol (4) and ganodermanondiol (6) showed cytotoxic effects on
      tested tumor cells. Of the compounds, lucialdehyde C (3) exhibited the most
      potent cytotoxicity against LLC, T-47D, Sarcoma 180, and Meth-A tumor cells with
      ED(50) values of 10.7, 4.7, 7.1, and 3.8 microg/ml, respectively.

PMID- 12045344
TI  - Two new acylated flavanone glycosides from the leaves and branches of Phyllanthus
      emblica.
AB  - Two new acylated flavanone glycosides, (S)-eriodictyol 7-O-(6"-O-trans-p
      coumaroyl)-beta-D-glucopyranoside (1) and (S)-eriodictyol 7-O-(6"-O-galloyl)-beta
      D-glucopyranoside (2) were isolated from the leaves and branches of Phyllanthus
      emblica together with a new phenolic glycoside, 2-(2-methylbutyryl)phloroglucinol
      1-O-(6"-O-beta-D-apiofuranosyl)-beta-D-glucopyranoside (3), as well as 22 known
      compounds. Their structures were determined by spectral and chemical methods.

PMID- 12045345
TI  - Patavine, a new arylnaphthalene lignan glycoside from shoot cultures of
      Haplophyllum patavinum.
AB  - A new arylnaphthalene lignan glycoside, patavine (1), together with five known
      lignans, justicidin B (2), diphyllin (3), tuberculatin (4), majidine (5), and
      arabelline (6) were isolated from shoot cultures of Haplophyllum patavinum. The
      structure of the new compound was elucidated by extensive one-dimensional (1D)
      and two-dimensional (2D) NMR experiments and mass spectrometry. The cytotoxicity
      of compounds 1, and 3-6 against LoVo human colon carcinoma cells was
      investigated.

PMID- 12045346
TI  - New pregnane glycosides from Cynanchum ascyrifolium.
AB  - Two new pregnane glycosides, cynascyrosides D and E, were isolated from the roots
      of Cynanchum ascyrifolium. The structures of these compounds were determined on
      the basis of spectroscopic and chemical evidence as cynajapogenin A 3-O-alpha-L
      cymaropyranosyl-(1-->4)-beta-D-digitoxopyranosyl-(1-->4)-beta-L-cymaropyranoside
      and cynajapogenin A 3-O-beta-D-glucopyranosyl-(1-->4)-alpha-L-diginopyranosyl-(1-
      >4)-beta-L-cymaropyranosyl-(1-->4)-beta-D-digitoxopyranoside.

PMID- 12045347
TI  - New renin inhibitors with pseudodipeptidic units in P(1)-P(1') and P(2')-P(3')
      positions.
AB  - A series of four new potential renin inhibitors has been synthesized. The
      structure of the compounds was designed in such a way as to produce agents
      resistant to enzymatic degradation, metabolically stable, possibly potent and
      with improved oral absorption. All positions of the 8-13 fragment of the human
      angiotensinogen were occupied by unnatural units (two unnatural amino acids in
      positions P(3) and P(2) and two pseudodipeptides in positions P(1)-P(1') and
      P(2')-P(3')). Both N- and C-terminal functions of the inhibitors were blocked
      with tert-Boc and ethyl ester groups. Their hydrophobicity evaluated as a log P
      value, calculated by a computer method, was 6.57 and 6.08 respectively. All
      peptides were obtained by the carbodiimide method in solution and purified by
      chromatography on the SiO(2) column. Their resistance to enzymatic degradation
      was assayed by determination of stability against chymotrypsin activity. The
      potency was measured in vitro by a spectrofluorimetric method (assay of Leu-Val
      Tyr-Ser released from the N-acetyltetradecapeptide substrate by renin in the
      presence of the inhibitor). All inhibitors were stable to chymotrypsin. Their
      IC(50) (M/l) values were: 9.6 x 10(-4) (12), 1.6 x 10(-5) (17), 1.0 x 10(-5) (22)
      and 1.0 x 10(-5) (23) respectively.

PMID- 12045348
TI  - 4-Hydroxy-6-methoxyaurones with high-affinity binding to cytosolic domain of P
      glycoprotein.
AB  - A series of 4-hydroxy-6-methoxyaurones and 4,6-dimethoxyaurones has been
      synthesised and tested for their binding affinity toward the nucleotide-binding
      domain of P-glycoprotein, an ABC (ATP-Binding Cassette) transporter which
      mediates the resistance of cancer cells to chemotherapy. These compounds differ
      from each other by the nature of the substituent on the aurone B-ring. The
      binding affinity seems to be linked to the nature of the substituent, as well as
      to the presence or the absence of a hydroxy group at position 4. The most active
      compounds were 4'-bromo-4-hydroxy-6-methoxyaurone and 4-hydroxy-4'-iodo-6
      methoxyaurone.

PMID- 12045349
TI  - New cyclic peptides from Citrus medica var. sarcodactylis SWINGLE.
AB  - Two new cyclic peptides were isolated from the fruit peels of Citrus medica var.
      sarcodactylis SWINGLE. Their structures were elucidated as cyclo(-Gly-Asp-Leu-Thr
      Val-Tyr-Phe-) and cyclo(-Gly-Leu-Pro-Trp-Leu-Ile-Ala-Ala-) by intensive two
      dimensional (2D) NMR analysis and chemical evidence.

PMID- 12045350
TI  - Cardiac glycosides from Erysimum cheiranthoides.
AB  - Three new cardiac glycosides named cheiranthoside VIII (1), cheiranthoside IX (2)
      and cheiranthoside X (3) were isolated from the seeds of Erysimum cheiranthoides.
      Based on spectroscopic data, the structures of 1-3 were characterized as
      strophanthidin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-antiaropyranoside,
      cheiranthidin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-boiviopyranoside and
      cheiranthidin 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-digitoxopyranoside,
      respectively. The aglycone moiety possessing a carboxyl group at C-10 of 2 and 3
      was regarded to be determined for the first time.

PMID- 12045351
TI  - Stilbene and 2-arylbenzofuran glucosides from the rhizomes of Schoenocaulon
      officinale.
AB  - Two stilbene glucosides, oxyresveratrol 2-O-beta-glucopyranoside and resveratrol
      3,4'-O,O'-di-beta-D-glucopyranoside, and a 2-arylbenzofuran glucoside,
      schoenoside, were isolated from the rhizomes of Schoenocaulon officinale, along
      with five known compounds, oxyresveratrol 3'-O-beta-D-glucopyranoside,
      oxyresveratrol, resveratrol 3-O-beta-D-glucopyranoside, mulberroside A and
      moracin M 3'-O-beta-D-glucopyranoside. The structural elucidations were based on
      analyses of both physical and spectroscopic data.

PMID- 12045352
TI  - A practical synthesis of L-ribose.
AB  - L-Ribose was synthesized by a simple four-step method with overall yield of 76.3%
      from a protected L-arabinose derivative, which is a compatible intermediate for
      the synthesis of L-deoxyribose. The key step of this strategy is the Swern
      oxidation and subsequent stereoselective reduction accompanied by inversion of
      the 2-hydroxy group of protected L-arabinose.

PMID- 12045353
TI  - Phenylethanoid and iridoid glycosides from Veronica persica.
AB  - A new phenylethanoid glycoside, persicoside (1) and three known phenylethanoid
      glycosides, acteoside (2), isoacteoside (3) and lavandulifolioside (4) were
      isolated from the aerial parts of Veronica persica. On the basis of spectral
      analyses, the structure of the new compound was elucidated to be 3,4-dihydroxy
      beta-phenylethoxy-O-[beta-D-glucopyranosyl-(1-->2)]-[beta-D-glucopyranosyl-(1-
      >3)]-4-O-caffeoyl-beta-D-glucopyranoside. Persicoside (1) and acteoside (2)
      exhibited radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl
      (DPPH) radical. Beside phenylethanoid glycosides, a hexitol, dulcitol (5) and
      seven known iridoid glucosides, aucubin (6), veronicoside (7), amphicoside (8), 6
      O-veratroyl-catalpol (9), catalposide (10), verproside (11) and verminoside (12)
      were isolated.

PMID- 12045354
TI  - New synthetic route to granulatimide and its structural analogues.
AB  - The Stille coupling reaction of stannylindole 12 with 4-iodoimidazole 13 (or 24)
      in the presence of PdCl(2)(PPh(3))(2) gave the corresponding indole-imidazole
      coupling product 14 (or 25), thereby affording a new synthetic approach to the
      alkaloid granulatimide (7), isolated from the Brazilian ascidian Didemnum
      granulatum, as well as its structural analogues, 10-methylgranulatimide (23), 17
      methylgranulatimide (30), 10,17-dimethylgranulatimide (31).

PMID- 12045355
TI  - Inhibitory effects of triterpene-azidothymidine conjugates on proliferation of
      human immunodeficiency virus type 1 and its protease.
AB  - The conjugates of some dicarboxylic acid hemiesters of triterpenes which show
      potent inhibition against human immunodeficiency virus type 1 protease (HIV-1 PR)
      with a reverse transcriptase inhibitor azidothymidine (AZT) or anti-HIV alkaloid
      FK 3000 were prepared, and their inhibitory activities were investigated against
      HIV-induced cytopathic effects (CPE) and HIV-1 PR. Most of the triterpene-AZT
      conjugates showed potent anti-HIV activity as well as moderate to potent PR
      inhibitory activity, though AZT itself showed no PR inhibitory activity at all.
      However, the triterpene-FK 3000 conjugates showed neither PR inhibitory activity
      nor anti-HIV activity.

PMID- 12045356
TI  - A comparison of the analysis of covariance (ANCOVA) and range-based approaches
      for assessing batch-to-batch variability of the stability of pharmaceutical
      products.
AB  - Stability data were generated by the Monte Carlo method, and batch-to-batch
      variability was evaluated by analysis of differences in slope and intercept
      according to the analysis of covariance (ANCOVA) approach recommended in the FDA
      Guidance. Using the same generated data, batch-to-batch variability was also
      evaluated by assessing the equivalence of shelf lives estimated for individual
      batches based on the range (Range-based approach) in order to compare the ability
      of the two approaches to detect stability differences among batches. The results
      of the study indicated that the Range-based approach can detect a 30% difference
      in the slope of degradation curves among batches with a similar beta error as the
      ANCOVA approach, provided that degradation data are obtained with assay errors
      below 0.5. The range-based approach appears to be useful as an alternative method
      to ANCOVA, if it is modified such that the variance of estimates is taken into
      account.

PMID- 12045357
TI  - Anti-inflammatory cytokines: expression and action in the brain.
AB  - Transforming growth factor-beta(1) (TGF-beta(1)) and interleukin (IL)-10 gene
      expression is equivocal in normal brain and upregulated in over a dozen central
      and peripheral diseases/disorders. The patterns of specific expression of
      cytokines differ in these diseases. Published data indicate that these cytokines
      are produced by and act on both neurons and glial cells. Although their actions
      are commonly viewed as 'anti-inflammatory', they protect neurons and downregulate
      the responses of glial cells to diseases/disorders in the absence of
      inflammation. Their actions counterbalance the actions of elevated IL-1 and/or
      tumor necrosis factor-alpha to maintain homeostasis. Their therapeutic potential
      will be realized by improving our understanding of their place in neural cytokine
      networks.

PMID- 12045358
TI  - Effects of social isolation on ehrlich tumor growth and tumor leukocyte
      infiltration in mice: evidence of participation of the submaxillary salivary
      gland.
AB  - OBJECTIVE: Considering previous studies on stress and Ehrlich tumor growth from
      our laboratory and also known cell growth and behavior-related properties of
      submaxillary salivary gland products, we studied the effects of stress by social
      isolation, in combination or not with sialectomy (submaxillary gland ablation),
      on growth and leukocyte infiltration into Ehrlich adenocarcinomas. METHODS: 5 x
      10(7) tumor cells/ml were inoculated into the footpads of mice and tumor growth
      was evaluated by measuring paw thickness on alternate days. Ten days after
      inoculation, tumors were harvested and processed for immunocytochemical analysis
      of tumor-infiltrating leukocytes (TIL) and nerve-like growth factor
      (NGF)/epidermal growth factor (EGF)-positive tumor cells. T and B lymphocyte, NK
      cell and macrophage percentages were calculated. RESULTS: Sialectomy slightly
      reduced tumor growth and caused a significant increase in NK cell infiltration of
      tumors (p < 0.05). Social isolation caused a highly significant enhancement of
      both tumor growth (p < or = 0.05) and percentage of macrophages infiltrating
      tumors (p < 0.05). Sialectomized isolated animals showed few significant changes
      in tumor growth rate (p < or = 0.05), but presented increased percentages of NK
      cells, macrophages and B lymphocytes (p < 0.05). A reduction in the percentage of
      NGF+ tumor cells was also observed (p < 0.05). All of these effects were seen
      only in 8-month-old mice, but not in younger animals. CONCLUSION: A possible link
      between salivary gland factors, tumor growth and TIL patterns was considered,
      suggesting that growth factors may modulate tumor leukocyte infiltration as well
      as tumor growth rate.

PMID- 12045359
TI  - Modulation of body temperature, interleukin-6 and leptin by oral contraceptive
      use.
AB  - OBJECTIVES: This study examined the hypothesis that oral contraceptives (OC)
      influence the production of thermoregulatory cytokines, i.e. interleukin-6 (IL
      6), soluble IL-6 receptor (sIL-6R), soluble glycoprotein 130 (s-gp130) and
      leptin, and that OC-induced changes in oral temperature (T(oral)) are associated
      with changes in plasma concentrations of these cytokines. To determine if
      increases in T(oral) are part of a cytokine-driven inflammatory (acute-phase)
      response, circulating concentrations of the hepatic acute-phase protein C
      reactive protein (CRP) were also measured. METHODS: Morning T(oral) were measured
      and blood samples were collected from 18 women (19- to 22-years-old) on two
      occasions: Once during active pill usage (quasi-luteal (QL) phase) and once when
      no active pills were taken (quasi-follicular (QF) phase). Plasma cytokine and CRP
      concentrations were measured by immunoassay. RESULTS: T(oral) and plasma leptin
      were higher during QL phase (36.4 +/- 0.1 degrees C, 9.3 +/- 1.0 ng/ml) than QF
      phase (36.1 +/- 0.1 degrees C, p < 0.01; 7.5 +/- 0.7 ng/ml, p < 0.01). Increases
      in T(oral) correlated with increases in plasma leptin (R = 0.55, p = 0.02) and
      with progestin dose (R = 0.47, p = 0.05) individually as well as with leptin and
      progestin combined in a multiple regression (R = 0.68, p = 0.01). Plasma IL-6
      correlated with progestin dose (R = 0.62, p = 0.006). Although there were no
      phase-related differences in plasma IL-6, sIL-6R, s-gp130, or CRP, the variation
      in CRP between individuals correlated with the IL-6 agonist/antagonist ratio
      combined with progestin dose in a multiple regression (R = 0.71, p = 0.01).
      CONCLUSIONS: These results (a) implicate leptin in basal thermoregulation; (b)
      indicate that progestins have a significant influence on circulating IL-6
      concentrations, and (c) are consistent with the concept that plasma CRP
      concentrations depend upon combined influences of progestins and bioavailable IL
      6.

PMID- 12045360
TI  - Regulation of corticotropin-releasing factor receptor type 2beta messenger
      ribonucleic acid by interleukin-1beta in rat vascular smooth muscle cells.
AB  - OBJECTIVE: Corticotropin-releasing factor receptor type 2 (CRF R2) messenger RNA
      (mRNA) expression in the rodent heart or vessels is modulated by exposure to
      urocortin and glucocorticoids. In addition, we previously found that incubation
      with a variety of cytokines, such as interleukin (IL)-1 and IL-6, and tumor
      necrosis factor-alpha also reduced CRF R2beta mRNA expression, with IL-1beta
      being the most effective. In this study, we further explored the regulation of
      CRF R2beta mRNA levels by IL-1beta in the rat vascular smooth muscle A7r5 cells.
      METHODS: A7r5 cells were incubated with IL-1beta, urocortin, or both for 6 h,
      after pre-incubating with or without anti-IL-1beta antibody (Ab) for 30 min, and
      then CRF R2beta mRNA levels were measured by RNase protection assay. Cells were
      incubated with lipopolysaccharides, IL-1beta, IL-6, dexamethasone, forskolin, or
      urocortin for 20 min, and then intracellular cAMP was measured by cAMP RIA.
      RESULTS: IL-1beta produced a significant time-dependent decrease in CRF R2beta
      mRNA levels. Combined urocortin and IL-1beta administration did not have
      synergistic effects on the decrease in CRF R2beta mRNA levels. IL-1beta Ab failed
      to block the ability of urocortin to regulate CRF R2beta mRNA levels, suggesting
      that urocortin regulated CRF R2beta mRNA levels via another pathway than IL-1beta
      production. Urocortin induced the intracellular cAMP production in A7r5 cells,
      while IL-1beta failed to induce it. CONCLUSION: The multifactorial regulation of
      CRF R2beta mRNA expression in the A7r5 cells serves to limit the inotropic and
      chronotropic effects of CRF R2 agonists such as urocortin during prolonged
      physical or immune challenge.

PMID- 12045361
TI  - Restraint stress-induced elevation of endogenous glucocorticoids decreases
      Peyer's patch cell numbers via mechanisms that are either dependent or
      independent on apoptotic cell death.
AB  - In this study, we investigated whether restraint stress induces either apoptotic
      cell death or lymphocyte migration in Peyer's patches. Exposure to stress induced
      a striking decrease in the number of CD3+CD4+, CD3+CD8+ and B220+ cells. Such
      decreases were accompanied by the enhanced induction of apoptosis in Peyer's
      patches. The apoptosis of Peyer's patch cells was completely reversed by
      pretreatment with either high or low doses of RU-486, a glucocorticoid receptor
      antagonist. In contrast, the stress-induced lymphopenia was little affected by
      administration of low doses of RU-486, although such lymphopenia was perfectly
      inhibited by treatment with high doses of RU-486. Taken together, these results
      suggest that the stress-induced lymphopenia in Peyer's patches is partly due to
      apoptotic cell death, although other systems such as lymphocyte migration, may
      contribute to such a reduction in the number of Peyer's patch cells.

PMID- 12045362
TI  - Plasma interleukin-1beta, prolactin, ACTH and corticosterone responses to
      endotoxin after damage of the anterior hypothalamic area.
AB  - This report concerns the use of an animal model described by us [J Submicrosc
      Cytol Pathol 1995;27:83-89] to investigate neural and endocrine sites for
      endotoxin (ENDO, E. coli 055:B5, 200 microg/100 g body weight in saline
      intravenously) effects on immunomodulatory hormone and cytokine release. Plasma
      interleukin-1beta (IL-1beta), prolactin (PRL), ACTH and corticosterone responses
      to ENDO after neurotoxic damage of neurons residing in the anterior hypothalamic
      area (AHA) were studied in freely behaving male rats. Excitotoxic cell damage in
      the AHA was produced by bilaterally injecting N-methyl-DL-aspartate (NMA) in
      artificial cerebrospinal fluid (aCSF) into this brain site. Injections of
      comparable volumes of aCSF alone served as controls for brain damage associated
      with the treatment. In both experimental brain manipulations before ENDO
      challenge the rise in plasma IL-1beta concentrations in response to ENDO was
      reduced by 2-fold at 1 h and 3- to 5-fold at 3 h when compared to controls.
      Nevertheless, experimental and control brain manipulations did not modulate the
      expected rise in corticosterone concentrations after ENDO exposure which rose 5
      fold above the baseline level in all animals. However, AHA manipulation did
      reduce plasma ACTH and prolactin concentrations differentially. Introduction of
      either NMA or the control injection of aCSF alone into AHA reduced plasma ACTH
      concentrations by 2-fold at 0.5 and 1 h after ENDO. However, there was a greater
      reduction in the rise of plasma PRL concentrations after ENDO found in NMA
      treated groups versus rats receiving control aCSF. These results demonstrate that
      variable-size hypothalamic damage (a larger lesion produced in AHA by NMA
      treatment vs. a smaller lesion control after aCSF) can result in a differential
      blunting of PRL, IL-1beta and ACTH release into blood in the face of robust,
      unmodulated corticosterone increases. In summary, these findings revealed a
      consistent predominant influence of ENDO on adrenal release of corticosterone as
      a concomitant to differential IL-1beta, ACTH and PRL release after AHA cell loss.
      In conclusion, these results constitute further evidence for hypothalamic
      orchestration of a balance between immunotropic and immunosuppressive
      neuroendocrine-immune events during acute bacterial infection of mammals.

PMID- 12045363
TI  - Medical education and the management of hypertension.

PMID- 12045364
TI  - The diagnosis of hypertension.
AB  - An argument can be made for modifying the recommendation in the sixth report of
      the Joint National Committee for Prevention, Detection, Evaluation, and Treatment
      of High Blood Pressure (JNC VI) for the measurement of blood pressure. If the
      blood pressure is taken in the erect position immediately after the patient
      enters the examination room, a much closer approximation of the ambulatory blood
      pressure is obtained. Another blood pressure taken immediately after assuming the
      supine position, and a third blood pressure 3-5 minutes after assuming the supine
      position, will then yield a basal equivalent to the JNC VI recommendation.
      Postural hypotension in older and diabetic patients can be unmasked by a final
      erect blood pressure. These procedures will allow a spectrum of blood pressures
      sufficient to establish the diagnosis of hypertension and monitor its treatment,
      without resorting to ambulatory blood pressure monitoring.

PMID- 12045365
TI  - Omapatrilat provides long-term control of hypertension: a randomized trial of
      treatment withdrawal.
AB  - Omapatrilat simultaneously inhibits neutral endopeptidase and angiotensin
      converting enzyme, increasing levels of vasodilatory peptides while decreasing
      production of angiotensin II. This study evaluated the clinical effects of
      withdrawal of omapatrilat after a patient's hypertension had been controlled
      (seated diastolic blood pressure <90 mm Hg) on omapatrilat for at least 6 months,
      with or without adjunctive antihypertensive medications. This double-blind study
      randomized 83 patients to receive either their established omapatrilat dose or
      placebo for 8 weeks; any concomitant antihypertensive medications were kept
      constant. Patients continuing on omapatrilat had no change in blood pressure.
      Patients whose chronic omapatrilat treatment was replaced by placebo had
      clinically important increases in both systolic (+16.5 mm Hg) and diastolic
      ((+9.6 mm Hg) blood pressures (both p<0.001). An increase in blood pressure was
      also seen in patients who were taking adjunctive antihypertensive medications
      prior to withdrawal of omapatrilat. This study demonstrates that when compared to
      withdrawal placebo, omapatrilat maintains clinically and statistically
      significant blood pressure reductions.

PMID- 12045366
TI  - Moderate sodium restriction enhances the pressor response to hyperlipidemia in
      obese, hypertensive patients.
AB  - The effect of dietary sodium restriction on insulin, lipids, and blood pressure
      has been controversial. Evidence suggests that adverse short-term effects in
      response to very low-salt diets do not persist long-term with modest sodium
      restriction. In this study, the effects of modest dietary sodium restriction (60
      and 120 mmol sodium) were measured for 3 weeks in 12 lean normotensives and 10
      obese hypertensives. Blood pressure, plasma lipids, and the pressor response to
      an infusion of Intralipid and heparin were obtained. In contrast to previous
      reports concerning very low-salt diets, obese hypertensives did not manifest a
      pressor response or an adverse lipid effect with moderate salt restriction. Obese
      hypertensives were not more salt-sensitive than lean normotensives and did not
      manifest a different hemodynamic response to 4-hour infusion of Intralipid and
      heparin while on the 120-mmol/day salt diet. During the 60-mmol/day salt diet,
      however, plasma triglycerides increased more in obese than in lean volunteers
      during the Intralipid and heparin infusion (398+/-38 vs. 264+/-18 mg/dL; p<0.05),
      and there were greater increases in mean blood pressure (12+/-2 vs. 7+/-2 mm Hg;
      p<0.05) and systemic vascular resistance (111+/-38 vs. 225+/-44 dyne.sec.cm-5) as
      well as a larger decrease in small artery compliance (22.5+/-0.6 vs. 20.4+/-0.6
      mL/mm Hg x 100; p<0.05). These data suggest that modest dietary sodium
      restriction in obese hypertensives does not adversely affect baseline blood
      pressure or lipids, but it does magnify their adverse lipid and hemodynamic
      response to fat loading.

PMID- 12045367
TI  - The quality of life of patients with hypertension.
AB  - The authors evaluated the self-reported quality of life in patients with systemic
      arterial hypertension and assessed whether clinicians and normotensive
      respondents from the general public appreciate the impact that hypertension has
      on health-related quality of life. A quality-of-life questionnaire was completed
      by 385 individuals: persons with hypertension (n=188), normotensive persons
      (n=148), and clinicians (n=49). A utility score, which represents one's self
      perceived health-related quality of life, was generated for each group by using
      standardized time tradeoff questionnaires. Quality of life with hypertension was
      judged to be significantly higher according to affected individuals (mean utility
      score, 0.980), compared with normotensive persons (mean utility score, 0.948) and
      clinicians (mean utility score, 0.942), who were asked to assume that they had
      hypertension (p<0.0005). Clinicians and normotensive individuals tend to
      overemphasize the impact that hypertension has on quality of life, as compared to
      affected patients. The relatively low impact that hypertensive individuals
      indicate high blood pressure has on their quality of life may contribute to their
      lack of compliance with treatment regimens.

PMID- 12045369
TI  - Importance of potassium in cardiovascular disease.
AB  - The pivotal role of potassium (K+) in cardiovascular disease and the importance
      of preserving potassium balance have become clinical hot points, particularly as
      relates to new and emerging cardioprotective and renoprotective therapies that
      promote potassium retention. Although clinicians may be aware of the critical
      nature of this relationship, quite frequently there is some uncertainty as to the
      best way to monitor potassium levels in the face of a host of pathologic states
      and/or accompanying drug therapies that affect serum levels and/or total body
      potassium balance. Moreover, guidelines for monitoring of serum potassium levels
      are at best tentative and oftentimes are translated according to the level of
      concern of the respective physician. To address these uncertainties, an expert
      group was convened that included representatives from multiple disciplines. They
      attempted to reach consensus on the importance of K+ in hypertension, stroke, and
      arrhythmias as well as practical issues on maintaining K+ balance and avoiding K+
      depletion. Because of the complexity of this topic, issues of hyperkalemia will
      be addressed in a forthcoming manuscript.

PMID- 12045368
TI  - Therapeutic considerations in the treatment of obesity hypertension.
AB  - Obesity, now recognized as an independent risk factor for cardiovascular disease,
      is closely associated with hypertension. Complex mechanisms link increasing body
      weight with increasing blood pressure. Treatment of the obese patient with
      hypertension requires consideration of physiologic changes related to obesity
      hypertension. Lifestyle modification, including weight reduction and increased
      physical activity, can directly influence blood pressure levels and improve blood
      pressure control in obese, hypertensive patients. Clinical trials are needed to
      determine the most effective antihypertensive drugs for the obese, hypertensive
      patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity
      hypertension, but additional long-term studies are needed to support their safety
      and efficacy.

PMID- 12045375
TI  - Premature termination of clinical trials--lessons learned.
AB  - Controlled clinical trials in cardiovascular disease are the cornerstone for
      therapeutic advances in this field of medicine. Since the introduction of the
      concept of controlled clinical trials there has been substantial progress in the
      design, conduct, and analysis of such studies. A growing awareness of ethical
      issues emerging from such trials has heightened public awareness, increased
      investigator scrutiny, and reinforced the need for interim data analysis. A
      benefit of such interim analyses is that either an entire clinical trial or a
      specific treatment limb can be stopped if the observed findings argue for
      premature termination. For example, highly positive findings, as were noted in
      the HOPE Study (Heart Outcomes Prevention Evaluation), led to its being stopped
      after 4.5 years of treatment, which was 1 year early. Alternatively, the
      doxazosin treatment limb of the ALLHAT (Antihypertensive and Lipid-Lowering
      Treatment to Prevent Heart Attack Trial) and the amlodipine treatment limb of
      AASK (African American Study of Kidney Disease and Hypertension) were stopped
      early because of negative findings with each respectively. Finally, economic
      considerations can enter into the decision to close a study early as was the case
      in the CONVINCE (Controlled Onset Verapamil Investigation of Cardiovascular End
      Points) trial. Most such decisions rely heavily on information obtained from
      independent data and safety monitoring boards. Such boards ensure patient safety
      by providing an unbiased ongoing review of data, which would otherwise be
      unavailable until a study's completion. Early termination of a clinical trial can
      have important clinical implications and, in particular, can redirect patterns of
      clinical practice.

PMID- 12045376
TI  - The history and politics of salt.

PMID- 12045377
TI  - Acupuncture in hypertension.

PMID- 12045378
TI  - Adrenal hyperplasia.

PMID- 12045380
TI  - Free radicals in heart failure: therapeutic targets for old and new drugs.

PMID- 12045381
TI  - Reactive oxygen species, mitochondria, and NAD(P)H oxidases in the development
      and progression of heart failure.
AB  - Reactive oxygen species (ROS) released acutely in large amounts have been
      traditionally implicated in the cell death associated with myocardial infarction
      or reperfusion injury. These ROS can be released from the cardiac myocyte
      mitochondria, xanthine oxidase, and the phagocytic nicotinamide adenine
      dinucleotide phosphate (NAD(P)H) oxidase. Interestingly, the chronic release of
      ROS has been recently linked to the development of left ventricular hypertrophy
      and heart failure progression. The chronic release of ROS appears to derive from
      the nonphagocytic NAD(P)H oxidase and mitochondria. Experimental data are
      accumulating suggesting that the release of ROS is required for the normal,
      physiologic activity of cardiac cells, but abnormal activation of the
      nonphagocytic NAD(P)H oxidase in response to neurohormones (angiotensin II,
      norepinephrine, tumor necrosis factor-a) has been shown to contribute to cardiac
      myocyte hypertrophy. Furthermore, the fibrosis, collagen deposition, and
      metalloproteinase activation involved in the remodeling of the failing myocardium
      are dependent on ROS released during the phenotypic transformation of fibroblasts
      to myofibroblasts associated with progression of end-stage heart failure. Future
      studies are necessary to identify the sources, mechanisms of activation of
      NAD(P)H oxidases, and downstream signaling targets implicated in the progression
      of chronic heart failure.

PMID- 12045382
TI  - The nitric oxide pathway and oxidative stress in heart failure.
AB  - Chronic heart failure is associated with pathophysiologic alterations in
      myocardial and vascular function. Accompanying these changes are increased
      oxidative stress and modulation of the nitric oxide pathway. The role of the
      nitric oxide(.) pathway in heart failure and the effect of its interaction with
      reactive oxygen species are complex, with diverse pathophysiologic implications
      in both the heart and the peripheral vasculature. This review discusses current
      information regarding the nitric oxide(.) pathway in heart failure and its
      relationship with increased oxidative stress.

PMID- 12045383
TI  - Heart failure, oxidative stress, and ion channel modulation.
AB  - The balance of reactive oxygen species (ROS) and nitric oxide, the cell redox
      state, appears to be important in the mechanisms of heart failure. This balance
      has significant impact on calcium-handling proteins, affecting excitation
      contraction coupling. Both ROS and nitric oxide appear to be elevated in heart
      failure and are accompanied by significant impairments in the number and function
      of calcium-handling proteins. These proteins contain sulfhydryl groups or
      disulfide linkages involving cysteine residues, making them susceptible to the
      action of oxidizing-reducing agents and nitrosylation, thereby altering their
      properties. Initial increases in nitric oxide may be an adaptive response to
      myocardial dysfunction, elevated cytokines, and increases in ROS, while a further
      increase in nitric oxide and overwhelming ROS can be damaging. Abundant nitric
      oxide and ROS can cause formation of peroxynitrite, a strong oxidant, or nitric
      oxide can activate alternate pathways aiding the ROS, causing impaired calcium
      handling contributing to contractile dysfunction.

PMID- 12045384
TI  - Genetic polymorphisms and oxidative stress in heart failure.
AB  - Heart failure results from various known cardiovascular diseases, such as
      coronary artery disease, or can be the result of an idiopathic dilated
      cardiomyopathy. It is of utmost importance for diagnostic, preventive, and
      therapeutic purposes to understand the cellular events that trigger the cascade
      of functional and structural changes that result in the development and
      progression of heart failure. Progress in unraveling the genetic background in
      both ischemic and nonischemic cardiomyopathies has been slow compared with that
      for monogenic diseases, such as some forms of hypertrophic cardiomyopathy or
      familial dilated cardiomyopathies. It is likely that susceptibility to and risk
      of progression of heart failure are both influenced by many genes acting in
      concert or independently. Among the diverse subcellular mechanisms implicated in
      the pathogenesis and progression of heart failure, reactive oxygen species play a
      major role. The search for genetic polymorphisms in clinical association studies
      in order to identify genotypes susceptible to develop and affect the progression
      to heart failure has been the focus of many investigations over the past several
      years. In this review, the authors summarize the current data in support of the
      role of various polymorphisms of genes related to oxidative stress in the
      susceptibility to develop heart failure, and its progression.

PMID- 12045385
TI  - Oxidative stress and endothelial dysfunction in heart failure.
AB  - The clinical syndrome of congestive heart failure (CHF) is characterized by
      abnormalities of left ventricular function and neurohormonal regulation, which
      are accompanied by effort intolerance, fluid retention, and decreased longevity.
      While an increased sympathetic tone and an activated renin-angiotensin system may
      contribute to the reduced vasodilatory capacity in patients with CHF, the
      important role of the endothelium in coordinating tissue perfusion has now been
      recognized. CHF is associated with endothelial dysfunction, as demonstrated by
      impaired endothelium-mediated vasodilation. Endothelial dysfunction in patients
      with CHF is a critical component in the systemic vasoconstriction and reduced
      peripheral perfusion that characterizes these patients. Endothelial regulation of
      vascular tone is mediated mainly by nitric oxide. Increased oxidative stress in
      patients with CHF is likely caused by decreased bioavailability of nitric oxide
      due to reduced expression of endothelial nitric oxide synthase and increased
      generation of reactive oxygen species. These react with nitric oxide in the
      setting of decreased antioxidant defenses that would normally clear these
      radicals, culminating in attenuated endothelium-dependent vasodilation in
      patients with CHF. Therapies that improve endothelial function have been shown to
      improve exercise tolerance and outcomes in patients with CHF. Endothelial
      dysfunction is thus an important target for future therapy in patients with CHF.

PMID- 12045386
TI  - Carvedilol: a nonselective beta blocking agent with antioxidant properties.
AB  - Despite advances in therapy, congestive heart failure is a major public health
      problem with a high mortality and morbidity. The benefits of beta blockers in
      slowing disease progression and decreasing mortality have recently been shown in
      large clinical trials. Oxidative stress contributes to disease progression in
      both post-myocardial reperfusion injury and dilated cardiomyopathy. Several
      medications are known to have antioxidant effects, including some angiotensin
      converting enzyme inhibitors. Carvedilol is a non-selective beta blocker with
      antioxidant properties approved for use in congestive heart failure.

PMID- 12045387
TI  - Doxazosin and congestive heart failure.
AB  - Doxazosin remains a commonly used antihypertensive medication, although its use
      has been tainted by recent findings from the Antihypertensive and Lipid-Lowering
      Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT was a large, simple
      trial, designed in a fashion to closely mimic clinical practice as it occurs in
      high-risk hypertensive patients aged 55 years or older. Its goals were to
      determine whether the incidence of the primary outcome--a composite of fatal
      coronary heart disease and nonfatal myocardial infarction--differed between
      treatment with a diuretic (chlorthalidone) (12.5-25.0 mg/day) and treatment with
      each of three other types of antihypertensive drugs-a calcium-channel blocker
      (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and a
      peripheral alpha-adrenergic blocker (doxazosin) (2-8 mg/day). Doxazosin was
      recently withdrawn from this trial after an interim analysis showed the secondary
      end point of combined cardiovascular disease to be 25% greater in patients on
      doxazosin than in those assigned to treatment with chlorthalidone. This finding
      was largely driven by congestive heart failure. The practicing clinician should
      not abandon doxazosin completely because of the ALLHAT findings, although these
      findings are indisputably important. These results represent an interim analysis
      and their application to clinical practice needs to occur carefully. A valued
      member of our therapeutic armamentarium need not be laid entirely to rest;
      rather, doxazosin should now be viewed as a secondary or tertiary
      antihypertensive therapy pending a more complete review of the ALLHAT data.

PMID- 12045390
TI  - Neonatal congenital heart disease and "complex" heart failure.
AB  - Hypoplastic left heart syndrome is a complex conglomerate of congenital cardiac
      abnormalities encountered in early life. Heart failure compensation and survival
      are intricately dependent on maintenance of ductal patency and avoidance of
      hyperoxic ventilation. While medical therapy is woefully inadequate, the staged
      Norwood procedure or cardiac transplantation remain the better options for
      treatment. Critically dependent on surgical outcomes, 5-year survival appears
      better with cardiac transplantation.

PMID- 12045391
TI  - Bone: a forgotten organ in lipidology?

PMID- 12045392
TI  - New factors in the regulation of adipose differentiation and metabolism.
AB  - Obesity and lipoatrophy are major risks for insulin resistance, type 2 diabetes
      and cardiovascular diseases. The molecular links between adipocyte dysfunction
      and metabolic disorders were elusive until the discovery that adipose tissue
      operates as an endocrine organ and releases factors targeting a wide range of
      organs. This article attempts to review the more recent advances from research on
      the transcriptional control of adipogenesis and on new adipocyte-secreted
      proteins that have been proposed as molecular links between adipose tissue and
      insulin resistance.

PMID- 12045393
TI  - Oxysterols in human circulation: which role do they have?
AB  - Oxysterols are oxygenated derivatives of cholesterol that are intermediates in
      cholesterol excretion pathways. They may also be regarded as transport forms of
      cholesterol and introduction of an additional hydroxyl group facilitates flux of
      cholesterol across cell membranes and the blood-brain barrier. According to
      current concepts, oxysterols are also mediating a number of cholesterol-induced
      metabolic effects. The recent discovery of nuclear receptors with an affinity for
      oxysterols has given support to this concept. Nuclear receptors such as liver X
      receptor alpha do have a role in cholesterol homeostasis, but there is still only
      indirect evidence that oxysterols are the physiological ligands. In this overview
      we report some recent advancements in our knowledge about the origin and
      metabolic fate of the quantitatively most important oxysterols occurring in the
      circulation. In addition, we discuss the possibility that some of these
      oxysterols may activate liver X receptors and regulate cholesterol homeostasis.

PMID- 12045394
TI  - Pathways for kidney-specific uptake of the steroid hormone 25-hydroxyvitamin D3.
AB  - Steroid hormones are believed to enter cells solely by free diffusion through the
      plasma membrane. However, recent work on the uptake of 25-hydroxyvitamin D3 into
      the kidney has identified an endocytic pathway that is responsible for the
      delivery of this steroid to renal tissues. This finding led to a new perception
      that endocytosis may play an important role in the cell-type-specific targeting
      and uptake of steroid hormones. In the present review, we describe the molecular
      components (e.g. steroid carriers, endocytic receptors and intracellular
      transport proteins) that constitute this novel pathway for tissue-specific uptake
      of vitamin D metabolites.

PMID- 12045395
TI  - Conjugated linoleic acid metabolism.
AB  - Conjugated linoleic acid (CLA) is a naturally occurring fatty acid that is
      produced by a bio-hydrogenation process in the rumen, and thus is present in
      dairy products and ruminant meat. In this case the predominant isomer formed is
      9cis,11trans. However, CLA includes 28 positional and geometrical isomers, of
      which only 9cis,11trans and 10trans,12cis have thus far been proven to possess
      biological activities. Both of these CLA isomers have been shown to undergo
      elongation and desaturation processes similar to those that occur with linoleic
      acid, maintaining the conjugated diene structure. There are evidences supporting
      the hypothesis that CLA metabolism may interfere with eicosanoid formation. Other
      metabolites with 16 carbon atoms (conjugated 16:2 and 16:3, which are probably
      derived from peroxisomal beta-oxidation of CLA and its metabolites, respectively)
      have been detected. This suggests an efficient metabolism of CLA and its
      metabolites in peroxisomes, which might be linked to their capacity to activate
      peroxisome proliferator-activated receptors.

PMID- 12045396
TI  - Recent studies on interactions between n-3 and n-6 polyunsaturated fatty acids in
      brain and other tissues.
AB  - Recent literature provides a basis for understanding the behavioral, functional,
      and structural consequences of nutritional deprivation or disease-related
      abnormalities of n-3 polyunsaturated fatty acids. The literature suggests that
      these effects are mediated through competition between n-3 and n-6
      polyunsaturated fatty acids at certain enzymatic steps, particularly those
      involving polyunsaturated fatty acid elongation and desaturation. One critical
      enzymatic site is a delta6-desaturase. On the other hand, an in-vivo method in
      rats, applied following chronic n-3 nutritional deprivation or chronic
      administration of lithium, indicates that the cycles of de-esterification/re
      esterification of docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6)
      within brain phospholipids operate independently of each other, and thus that the
      enzymes regulating each of these cycles are not likely sites of n-3/n-6
      competition.

PMID- 12045397
TI  - Cytochrome P450 pathways of arachidonic acid metabolism.
AB  - Cytochrome P450s metabolize arachidonic acid to hydroxyeicosatetraenoic acids and
      epoxyeicosatrienoic acids. These eicosanoids are formed in a tissue and cell
      specific manner and have numerous biological functions. Of major interest are the
      opposing actions of hydroxyeicosatetraenoic and epoxyeicosatrienoic acids within
      the vasculature. Regio- and stereoisomeric epoxyeicosatrienoic acids have potent
      vasodilatory properties while 20-hydroxyeicosatetraenoic acid is a potent
      vasoconstrictor. Both effects are mediated through actions on large-conductance
      Ca2+-activated K+ channels. Cytochrome P450-derived eicosanoids are also
      important in the regulation of ion transport, and have recently been shown to
      influence a number of fundamental biological processes including cellular
      proliferation, apoptosis, inflammation, and hemostasis. The formation of these
      functionally relevant eicosanoids is tightly controlled by the expression and
      activity of the cytochrome P450 epoxygenases and hydroxylases. In addition,
      soluble epoxide hydrolase catalyzes the hydrolysis of epoxyeicosatrienoic acids
      to dihydroxyeicosatrienoic acids, and the activity of this enzyme is a critical
      determinant of tissue epoxyeicosatrienoic and dihydroxyeicosatrienoic acid
      levels. The intracellular balance between epoxyeicosatrienoic,
      dihydroxyeicosatrienoic and hydroxyeicosatetraenoic acids influences the
      biological response to these eicosanoids and alterations in their levels have
      recently been associated with certain pathological conditions. The involvement of
      the cytochrome P450-derived eicosanoids in a wide array of biological functions
      and the observation that levels are altered in pathological conditions suggest
      that the enzymes involved in the formation and degradation of these fatty acids
      may be novel therapeutic targets.

PMID- 12045398
TI  - Effect of high-density lipoproteins on the expression of adhesion molecules in
      endothelial cells.
AB  - There are several potential mechanisms by which HDLs protect against
      atherosclerosis. One relates to the ability of HDLs to promote the efflux of
      cholesterol from macrophages. Another is the ability of HDLs to inhibit one of
      the earliest events in the development of atherosclerosis, namely the expression
      of vascular cell adhesion molecules in activated endothelial cells. This property
      has been reported in vitro in studies with both native and reconstituted HDLs.
      The inhibitory activity of reconstituted HDLs is influenced by the phospholipid
      composition of the particles. An inhibition of endothelial cell adhesion molecule
      expression has also been observed in some (but not all) studies conducted in vivo
      in mice and pigs. The mechanism of this potentially anti-atherogenic effect of
      HDLs remains uncertain, as does its contribution to the cardioprotective effects
      of HDLs in vivo.

PMID- 12045399
TI  - Lipid peroxidation in neurodegeneration: new insights into Alzheimer's disease.
AB  - Imbalances of oxidative homeostasis and lipid peroxidation have been revealed as
      important factors involved in neurodegenerative disorders such as Alzheimer's
      disease. The brains of patients with Alzheimer's disease contain increased levels
      of lipid-peroxidation products such as 4-hydroxy-2-nonenal or acrolein, and
      enhanced lipid peroxidation can also be detected in cerebrospinal fluid and
      plasma from such patients. Recent research revealed that the interplay of
      transition metals, amyloid-beta peptide and lipid peroxidation might be
      responsible for increased oxidative stress and cell damage in this disease. In
      particular, the contrasting roles of amyloid-beta peptide, as a possible
      transition metal-chelating antioxidant for lipoproteins and a pro-oxidant when
      aggregated in brain tissue, has been the focus of discussion recently. In this
      context, lipid peroxidation has to be seen as an important part of the
      pathophysiological cascade in Alzheimer's disease, and its measurement in body
      fluids might serve as a therapy control for Alzheimer's disease and other
      neurodegenerative diseases.

PMID- 12045400
TI  - Metabolic effects of thia fatty acids.
AB  - Thia substituted fatty acids are saturated fatty acids which are modified by
      insertion of a sulfur atom at specific positions in the carbon backbone. During
      the last few years pleiotropic effects of the 3-thia fatty acid
      tetradecylthioacetic acid have been revealed. The biological responses to
      tetradecylthioacetic acid include mitochondrial proliferation, increased
      catabolism of fatty acids, antiadiposity, improvement in insulin sensitivity,
      antioxidant properties, reduced proliferation and induction of apoptosis in
      rapidly proliferating cells, cell differentiation and antiinflammatory action.
      These biological responses indicate that tetradecylthioacetic acid changes the
      plasma profile from atherogenic to cardioprotective. As a pan-peroxisome
      proliferator-activated receptor ligand, tetradecylthioacetic acid regulates the
      adipose tissue mass and the expression of lipid metabolizing enzymes,
      particularly those involved in catabolic pathways. In contrast, circumstantial
      evidences suggest that peroxisome proliferator-activated receptor-independent
      metabolic pathways may be of importance for the antioxidant, antiproliferative
      and antiinflammatory action of tetradecylthioacetic acid.

PMID- 12045401
TI  - Roles of peroxisome proliferator-activated receptor gamma in lipid homeostasis
      and inflammatory responses of macrophages.
AB  - Monocytes play a critical role in atherogenesis by their inflammatory signals and
      differentiation into macrophage foam cells through cholesterol accumulation. The
      seminal finding of high levels of the peroxisome proliferator-activated receptor
      gamma in macrophage foam cells has opened up the prospect that its ligands, most
      importantly the thiazolidinedione class of drugs, might directly influence the
      development of atheromatous lesions. The present review weighs the growing
      evidence on regulation of both inflammatory responses and cholesterol homeostasis
      in macrophages by peroxisome proliferator-activated receptor gamma ligands with
      regard to their overall impact as antiatherogenic agents.

PMID- 12045402
TI  - Nutrition and metabolism.

PMID- 12045403
TI  - Genetics and molecular biology: peroxisome proliferator-activated receptor gamma
      still full of surprises.

PMID- 12045404
TI  - Lipid metabolism.

PMID- 12045405
TI  - Hyperlipidaemia and cardiovascular disease.

PMID- 12045406
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 12045407
TI  - Therapy and clinical trials: type 2 diabetes: lifestyle and beyond.

PMID- 12045408
TI  - All concord's born of contraries.

PMID- 12045409
TI  - Outpatient monitoring of asthma.
AB  - Monitoring asthma outcomes is an essential step to the successful implementation
      of national asthma guidelines. Symptoms, airflow obstruction and exacerbations
      can be monitored by patients with asthma and by physicians. Patients who practise
      self-monitoring in conjunction with use of a written action plan and regular
      medical review have significantly fewer hospitalizations, emergency room visits
      and lost time from work. Additional monitoring tools are under evaluation, and
      these include measures of airway responsiveness, airway inflammation, and
      Internet-based monitoring systems.

PMID- 12045410
TI  - Early predictors of asthma.
AB  - A number of recent cohort and cross-sectional studies have contributed
      substantial knowledge to factors that influence the early development of asthma.
      Here, we summarize the recent evidence for the role of early life events such as
      prenatal factors, infections, diet and allergen exposure, and discuss the
      implications for future preventative strategies.

PMID- 12045411
TI  - The diagnosis and management of asthma is much tougher in older patients.
AB  - Half the elderly individuals with asthma have not been diagnosed, yet their
      quality of life is substantially impaired. Primary care physicians should,
      therefore, be encouraged to ask about respiratory symptoms in elderly patients,
      and then perform office spirometry for those with symptoms. Airway obstruction
      increases the likelihood of asthma, but the lack of a 'significant' acute
      bronchodilator response is clinically meaningless. Methacholine challenge testing
      is safe and useful for detecting asthma in patients with normal baseline
      spirometry. Only one in five life-long smokers ever develops chronic obstructive
      pulmonary disease, so elderly smokers should also be evaluated for reversible
      airways obstruction. A normal diffusing capacity test will rule out emphysema in
      current and former smokers. Elderly individuals whose asthma has been diagnosed
      are often receiving sub-optimal treatment, resulting in poor asthma control and a
      high death rate. Co-morbidities (recognized or not) are the rule in elderly
      patients, and these conditions, or the drugs taken to treat them, may exacerbate
      asthma. Conversely, bronchodilators and corticosteroids used to treat asthma
      often worsen co-morbid conditions, such as osteoporosis, ocular disease, and
      cardiac arrhythmias. Therefore, extra caution is needed when treating elderly
      asthmatic patients, and objective monitoring of their response to each new asthma
      medication is important.

PMID- 12045413
TI  - Role of the specialist in the treatment of asthma.
AB  - The preponderance of literature supports the efficacy of specialist care for
      asthma. Not every patient with asthma needs to be treated by a specialist,
      however. An optimal health care delivery model for asthma (i.e. one that provides
      high quality care that is cost effective) requires some mix of primary and
      specialty services. A tiered model of care in which the primary care physician
      acts as the first point of contact and decision-maker with regard to referral and
      that includes asthma specialists, including allergists, pulmonologists, and other
      health care professionals with expertise in asthma, appears to be a reasonable
      solution. The number of studies that compare various models for organizing asthma
      care is limited, however. Thus, further research is needed to determine how best
      to align the roles of primary care physicians, allied health professionals, and
      subspecialists in order to ensure seamless communication and cost-effective care
      that is targeted to individual patient needs.

PMID- 12045412
TI  - Clinical pathways in treatment of asthma.
AB  - Although the number of medications for the treatment of status asthmaticus is
      relatively limited, strategies for the management of acute asthma vary widely
      both among and within institutions. The choice of drugs, doses, timing of
      administration, duration of treatment, and assessment measures are often left to
      the discretion of individual physicians; plans are often not formulated on the
      basis of data showing efficacy, but rather on local availability and the
      experience and preference of physicians. The elimination of treatment that adds
      cost but not improved quality of care can be an effective strategy to optimize
      the care of acute asthma.

PMID- 12045414
TI  - An update on the health economics of asthma and allergy.
AB  - Health economics is receiving more attention as decision-makers--whether
      purchaser, physician, or patient--are looking for a more comprehensive
      understanding of the impact of adopting new healthcare strategies. In this
      article we review the recent advances in the health economics of asthma and
      allergy. In burden of illness studies, estimates of the economic burden of asthma
      and allergy were reported from countries and regions not previously detailing
      these costs. There were economic evaluations comparing medications and those that
      evaluated disease management programs. The recent studies of pharmaceuticals have
      focused on evaluating the cost-effectiveness of various controller medications
      for the treatment of asthma. Although mostly observational, such studies increase
      the evidence that these medications are relatively cost-effective. A few recent
      economic evaluations have been published examining disease management and
      education programs. These studies are generally long-term evaluations and have
      not shown consistent health economic impact. The field of health economics in
      asthma and allergy continues to evolve and aims to provide information to aid in
      decision making.

PMID- 12045415
TI  - Monitoring adherence to the therapy of asthma.
AB  - Acceptance of current treatment guidelines by physicians and adherence to the
      recommended clinical regimens by patients are essential for effective asthma
      therapy. Treatment plans must be based on up-to-date management guidelines and
      should comprise a strategy for the evaluation and support of patient adherence.
      Monitoring of adherence with electronic devices enables physicians to base
      clinical decisions on reliable and objective data. Assessment of prescribing
      quality should be used to improve treatment of all patients.

PMID- 12045416
TI  - The impact of maternal diets during breastfeeding on the prevention of food
      allergy.

PMID- 12045417
TI  - Update on the clinical features of food-induced anaphylaxis.
AB  - Food-induced anaphylaxis has become the leading cause of anaphylactic reactions
      that occur outside hospital. We introduce the present review with a definition of
      food-induced anaphylaxis, including its prevalence and proposed etiology. Second,
      we discuss an entity that is increasingly being recognized: exercise-induced food
      anaphylaxis, which may be triggered by specific foods or at times where no
      specific food has been identified. Third, we review current attempts to identify
      specific food antigens that are responsible for anaphylaxis to well-known
      triggers (i.e. peanut, as well as more unusual antigens). Fourth, we discuss
      current treatment options available (i.e. patient education, food avoidance,
      acute symptom recognition, and early use of self-administered epinephrine).
      Additionally, we discuss outcome data regarding the morbidity and mortality
      related to food allergy and anaphylaxis. Finally, information regarding
      experimental immunomodulatory therapy is presented.

PMID- 12045418
TI  - Cow's milk allergy in infancy.
AB  - Cow's milk allergy affects approximately 2% of infants under 2 years of age. This
      review summarizes the recent advances in understanding its pathophysiology and
      immunological mechanisms. Apart from IgE-mediated atopic manifestations, T cell
      mediated reactions have been demonstrated in infants with cow's milk allergy. The
      clinical spectrum ranges from immediate-type reactions, presenting with urticaria
      and angioedema to intermediate and late-onset reactions, including atopic
      dermatitis, infantile colic, gastro-oesophageal reflux, oesophagitis, infantile
      proctocolitis, food-associated enterocolitis and constipation. The exact
      mechanisms of these disorders are still poorly understood. Double-blind, placebo
      controlled food challenge, the definitive diagnostic test for cow's milk allergy,
      is increasingly being replaced by the measurement of food-specific antibodies, in
      combination with skin-prick or atopy patch testing. The treatment of cow's milk
      allergy relies on allergen avoidance and hypoallergenic formulae, or maternal
      elimination diets in breast-fed infants.

PMID- 12045419
TI  - Recent advances in peanut allergy.
AB  - Peanut remains preeminent as the food allergen most associated with severe and
      fatal allergic reactions. Reactions are frequent despite patients' best efforts
      to avoid peanut. In the future, better information sharing and communication
      between families and both schools and restaurants may lead to a decrease in the
      rate of severe reactions induced by exposure to peanut outside the home. Reaction
      severity may increase over time but up to 25% of young peanut allergic
      individuals may outgrow their peanut allergy. Personalized care plans and
      education programmes may have an impact on avoidance of peanut and on the
      appropriate responses of caregivers. Peanut's allergenicity may be affected by
      the method of cooking, with roasted peanuts appearing more allergenic than boiled
      or fried peanuts. Immunotherapy with modified peanut allergens and DNA based
      vaccines may soon move from animal studies to clinical trials.

PMID- 12045420
TI  - Clinical features of cross-reactivity of food allergy caused by fruits.
AB  - Fruits are increasingly recognized as a cause of food allergy. The wide cross
      reactivity among these foods has been extensively studied. In this review we will
      focus on studies addressing the clinical relevance of cross-reactivity among
      fruits, the diagnostic management of patients complaining of reactions to
      multiple fruits, and adequate dietary recommendations.

PMID- 12045421
TI  - Experimental analysis of eosinophil-associated gastrointestinal diseases.
AB  - Eosinophil infiltration into the gastrointestinal tract occurs in a wide range of
      diseases. However, the underlying cellular and molecular mechanisms involved in
      eosinophil migration and the role of eosinophils in disease pathogenesis are
      largely unknown. Recent studies using experimental models of eosinophil
      associated gastrointestinal allergy have revealed differential roles for IL-5 and
      eotaxin in the modulation of eosinophil accumulation into various regions of the
      gastrointestinal tract. Furthermore, such studies have revealed a possible role
      for eosinophils in the pathogenesis of gastrointestinal disorders. The present
      review describes the clinical manifestations of various eosinophil-associated
      gastrointestinal disorders and the current understanding of the role of IL-5 and
      eotaxin in the allergic inflammatory response, and the participation of the
      eosinophilic granulocyte in the expression of disease.

PMID- 12045423
TI  - Evolving role of the atopy patch test in the diagnosis of food allergy.
AB  - The atopy patch test has developed into a valuable additional tool in the
      diagnostic work-up of food allergy in infants and children with atopic
      dermatitis. A positive atopy patch test may help to prevent imposing restrictive
      and unnecessary diets after misjudging late reactions by clinical assessment
      alone. Furthermore, the combination of positive atopy patch tests together with
      defined levels of specific IgE makes double-blind, placebo-controlled food
      challenges superfluous in some cases. However, several open questions indicate
      the need for further studies.

PMID- 12045422
TI  - Genetically engineered foods: implications for food allergy.
AB  - The products of agricultural biotechnology, including such common foods as corn
      and soybeans, are already reaching the consumer marketplace. Consumer exposure to
      such foods is already fairly significant, particularly in the USA. Thus far, no
      reports exist regarding allergic reactions to the crops that have been approved
      for introduction into the food supply. These crops have been modified to only a
      minor extent by comparison with their traditional counterparts, and the level of
      expression of new and novel proteins is quite low. Thus, consumer exposure to
      these novel proteins is very low and unlikely to result in allergic
      sensitization. Nevertheless, foods produced through agricultural biotechnology
      must be assessed for safety, including their potential allergenicity, before they
      may be approved by worldwide regulatory agencies for entry into the food supply.
      However, the adequacy of the current approach to the assessment of the potential
      allergenicity of foods produced through agricultural biotechnology has been the
      subject of considerable scientific and regulatory debate.

PMID- 12045424
TI  - Improving in-vitro tests for the diagnosis of food hypersensitivity.
AB  - Food hypersensitivity reactions affect up to 8% of children under 3 years of age
      and approximately 2.5% of the general United States population. Food allergic
      disorders may be subdivided into either IgE-mediated or cell-mediated reactions.
      The diagnostic 'gold standard' of 'symptomatic' food allergies remains the
      blinded oral food challenge because of the poor specificity of patient histories,
      skin testing and standard radioallergosorbent tests, and the outcomes of
      elimination diets. Little progress has been made in the development of in-vitro
      tests for the diagnosis of cell-mediated food hypersensitivities. However, new
      developments in in-vitro technologies have improved the capabilities of these
      tests to diagnose IgE-mediated reactivity and perhaps predict the development of
      future 'tolerance', i.e. 'outgrowing' the allergy.

PMID- 12045425
TI  - Role of probiotics in food hypersensitivity.
AB  - The definition of probiotics has evolved concomitant with a resurgence of
      research interest in host-microbe crosstalk. The original definition stated that
      the live active culture beneficially affects the host by improving its intestinal
      microbial balance, while current conceptions are based on target- and site-
      specific effects of clearly defined strains. The establishment of normal
      microbiota in the intestine represents a key process whereby the intestinal
      milieu is kept disease-free as it performs its dual function: mounting an
      inflammatory response to pathogens and maintaining hyporesponsiveness to
      innocuous antigens. Probiotic therapy is based on this concept of a healthy well
      balanced gut microbiota. The probiotic performance of strains differs, however.
      Different bacteria have clearly defined adherence sites and immunological effects
      and divergent effects in the healthy versus inflamed mucosa. Hence,
      notwithstanding recent demonstrations of the important immunoregulatory potential
      of the healthy well-balanced gut microbiota, current probiotic research is
      directed towards identification of specific strains with anti-allergenic
      potential.

PMID- 12045427
TI  - Current readings in nuclear medicine.

PMID- 12045426
TI  - Novel approaches for the treatment of food allergy.
AB  - At present there is no effective therapy for IgE-mediated food allergy, and
      patients must rely upon food-allergen avoidance. Unfortunately, the accidental
      ingestion of allergen-containing foods leading to potentially severe reactions is
      common. Definitive therapies for food allergy are desperately needed. Although
      rush immunotherapy has been reported to induce tolerance in some patients, the
      rate of maintenance of tolerance was low, and there was an undesirably high
      incidence of adverse reactions. New knowledge of the immunological mechanisms
      underlying allergic disease has expanded the potential therapeutic options for
      food allergy. The establishment of animal models of food hypersensitivity, which
      include sensitization by the oral route and anaphylaxis upon oral challenge, have
      facilitated the investigation of therapies for food allergy. Novel approaches
      under investigation include the reduction of IgE by the infusion of anti-IgE
      antibodies, vaccination with plasmid DNA, the use of anti-allergy
      immunostimulatory sequences, cytokines and bacterial agents, immunotherapy with
      mutated proteins and peptides, and complementary medicine such as Chinese herbs.

PMID- 12045428
TI  - Utility of Tc-99m human polyclonal immunoglobulin G scintigraphy for assessing
      the efficacy of yttrium-90 silicate therapy in rheumatoid knee synovitis.
AB  - PURPOSE: The aim of this study was to determine the utility of Tc-99m human
      polyclonal immunoglobulin G (HIG) scintigraphy for evaluating the efficacy of
      yttrium-90 (Y-90) silicate therapy in rheumatoid knee synovitis. MATERIALS AND
      METHODS: Fifteen patients (13 women, 2 men; mean age, 53.5 +/- 8.4 years) with
      rheumatoid arthritis had radionuclide synovectomy using 185 MBq (5 mCi) Y-90
      silicate to evaluate 24 knee joints with chronic persistent synovitis. Radiologic
      and clinical evaluations and Tc-99m HIG scans were performed in each patient
      before radionuclide synovectomy. Each patient was reassessed 3, 6, 9, and 12
      months after therapy using clinical examination and Tc-99m HIG scintigraphy.
      RESULTS: In 14 of 24 knee joints (4 Larsen stage I, 10 Larsen stage II) that had
      excellent or good clinical responses to Y-90 silicate therapy, the Tc-99m HIG
      index values 3 months after treatment were significantly lower than the
      pretreatment index values (P < 0.001). In 13 of these 14 joints, these low index
      values and clinical results remained constant throughout the 1 year of follow-up.
      One patient (1 of the 14 knee joints) experienced severe pain and swelling as a
      result of recurrent arthritis at 9 months, and the Tc-99m HIG index value
      increased at 9 months and remained high 12 months after therapy. In 10 of 24 knee
      joints (4 Larsen stage II, 6 Larsen stage III) that had a fair or poor clinical
      response, Tc-99m HIG index values were statistically similar before and after
      radionuclide therapy. CONCLUSIONS: Quantitative Tc-99m HIG scintigraphy is a
      valuable method for assessing the efficacy of Y-90 silicate therapy in rheumatoid
      knee synovitis.

PMID- 12045429
TI  - Ga-67 SPECT to detect endocarditis after replacement of an aortic valve.
AB  - Ga-67 SPECT was crucial in making the diagnosis of infectious endocarditis in a
      28-year-old man with a history of aortic valve replacement who was referred to
      the nuclear medicine service because of persistent fever. In the planar left
      anterior oblique view, an area of slight, diffuse activity was noted. The shape
      and site of the infectious focus were well defined by Ga-67 SPECT. After Ga-67
      imaging, results of a computed tomographic (CT) scan were negative and the
      patient was treated with antibiotics and discharged from the hospital after
      showing clinical improvement. However, the fever returned and he was readmitted.
      A second Ga-67 SPECT was also positive, but a spiral CT scan showed only minor
      inflammatory changes. Finally, transesophageal ultrasonographic images suggested
      vegetation on the prosthetic valve. Cultures of the graft and the valve were
      obtained surgically and showed staphylococcal endocarditis. Exaggerated
      confidence in negative CT scan results led to unnecessarily delayed surgical
      treatment of the infection. Ga-67 SPECT was a powerful noninvasive tool in the
      diagnosis of infectious complications after prosthetic valve surgery.

PMID- 12045430
TI  - Tc-99m sulfur colloid and Tc-99m tagged red blood cell methods are comparable for
      detecting lower gastrointestinal bleeding in clinical practice.
AB  - PURPOSE: The objective of this study was to determine whether the Tc-99m red
      blood cells (Tc-99m RBC) method has a true advantage over the Tc-99m sulfur
      colloid (Tc-99m SC) technique in a busy clinical practice for detecting and
      localizing lower gastrointestinal bleeding sites. METHODS: Three hundred fifty
      nine consecutive gastrointestinal bleeding studies performed during the past 4
      years were reviewed retrospectively. One hundred ninety-three scans were obtained
      with Tc-99m SC (scan duration, 30 minutes) and 138 studies were performed after
      the administration of Tc-99m RBC (scan duration, 1 hour). In addition, 28
      examinations with Tc-99m SC were followed immediately by Tc-99m RBC scans for a
      duration of several hours. The results of the two methods were analyzed and the
      performance of the two techniques was compared. RESULTS: Among 193 scans
      performed using the Tc-99m SC method, 47 (24.4%) successfully identified the
      location of the bleeding site, whereas in 138 scans performed using Tc-99m RBC,
      38 (27.5%) were successful for this purpose. In the remaining 28 scans in which
      the Tc-99m SC scan was followed by the Tc-99m RBC study, only 4 (14.3%) positive
      bleeding sites were identified after a prolonged imaging period. DISCUSSION: The
      theoretical advantages of the Tc-99m RBC technique compared with the Tc-99m SC
      method cannot be substantiated by this study. Our findings suggest that the
      efficacy of these two methods is nearly equal at a practical level. CONCLUSION:
      The simpler and cost-effective Tc-99m SC method is as efficient as the Tc-99m RBC
      method when the scanning time is limited to 1 hour and optimal imaging and
      interpretation schemes are used.

PMID- 12045432
TI  - Riedel's thyroiditis and retroperitoneal fibrosis in multifocal fibrosclerosis:
      positron emission tomographic findings.
AB  - PURPOSE: The authors describe F-18 fluorodeoxyglucose positron emission
      tomographic (FDG PET) imaging features of Riedel's thyroiditis and
      retroperitoneal fibrosis in a patient with multifocal fibrosclerosis. MATERIALS
      AND METHODS: A 41-year-old woman in whom Riedel's thyroiditis had been diagnosed
      7 months earlier was examined for fatigue, anorexia, and lower back pain,
      irradiating to the abdomen. Abdominal sonography and computed tomography showed a
      retroperitoneal mass. A biopsy of this mass showed histopathologic findings of
      retroperitoneal fibrosis. FDG PET was performed to evaluate the activity of the
      retroperitoneal fibrosis and to screen for other areas of fibrosclerosis.
      RESULTS: The FDG-PET images showed an intense hypermetabolic abdominal mass
      surrounding the aorta and increased glucose metabolism in the thyroid. No other
      sites of abnormal FDG metabolism were noted. These abnormalities disappeared
      after 4 months of steroid therapy. CONCLUSIONS: Sites of multifocal
      fibrosclerosis can be demonstrated by FDG PET, probably as a result of active
      inflammation involving lymphocytes, plasma cells, and fibroblast proliferation.
      FDG PET can help to establish the diagnosis of multifocal fibrosclerosis and
      evaluate the activity and patient response to corticosteroid therapy.

PMID- 12045431
TI  - Soft tissue metastases and lung cancer recurrence detected by Tc-99m depreotide
      scintigraphy.
AB  - A 63-year-old woman with previously treated stage I lung cancer was reexamined 5
      years later for recurrence. A conventional work-up using computed tomographic
      scanning and transbronchial biopsy showed nothing abnormal. A Tc-99m depreotide
      scan, however, led to a noninvasive diagnosis of lung cancer recurrence with
      metastases, and it directed a noninvasive tissue diagnosis.

PMID- 12045433
TI  - Bone scintigraphy in mycobacterium avium osteomyelitis: a case report.
AB  - A 30-year-old woman who had a destructive Mycobacterium avium complex infection
      in the left inguinal fossa affecting the pubic bone underwent three-phase bone
      scanning to identify other possibly affected sites. Multiple skeletal lesions
      were seen scattered throughout the vertebral column, sternum, and pelvis. This
      case is presented to describe a rare extensive metastatic M. avium complex
      infection in an immunocompromised patient.

PMID- 12045434
TI  - Radionuclide three-phase whole-body bone imaging.
AB  - PURPOSE: To describe the radionuclide three-phase whole-body bone imaging
      (TPWBBI) technique and discuss the usefulness of its application. MATERIALS AND
      METHODS: TPWBBI was performed after a single intravenous injection of 555 to 925
      MBq (15 to 25 mCi) Tc-99m MDP. Whole-body arterial flow (phase one) followed by
      blood-pool and tissue perfusion (phase two) images were obtained with the moving
      detector head speed set at 150 cm/minute and 40 cm/minute, respectively.
      Conventional whole-body static bone images (phase three) were obtained 3 hours
      later. RESULTS: When 542 consecutive TPWBBI results were reviewed, 394 (166
      extraskeletal and 228 skeletal) abnormalities were detected during phases one and
      two. The 166 extraosseous lesions included vascular diseases: abdominal aortic
      aneurysms and peripheral vascular diseases and renal abnormalities, liver
      abnormalities, ascites, and pleural effusions. Many of these were incidentally
      detected clinically significant findings and would not have been identified on
      conventional static bone images. It helps to differentiate among acute and
      chronic fractures, active and inactive inflammatory diseases such as arthritis or
      osteomyelitis, and Paget's disease. CONCLUSIONS: With a single injection of Tc
      99m MDP, whole-body images obtained in the arterial phase, the blood-pool and
      tissue perfusion phase, and the static bone phase can identify many clinically
      significant skeletal and soft tissue abnormalities. TPWBBI can differentiate
      between active and inactive phases of different disease processes and thereby
      provide a diagnosis that is more specific than a conventional single-phase bone
      scan. It may be applicable as a tool for nuclear physical examination.

PMID- 12045435
TI  - Lack of effect of a bisphosphonate (pamidronate disodium) infusion on subsequent
      skeletal uptake of Sm-153 EDTMP.
AB  - Patients who are candidates for samarium-153
      ethylenediaminetetramethylenephosphonic acid (Sm-153 EDTMP) therapy often receive
      monthly infusions of pamidronate disodium or other bisphosphonates. Because both
      drugs are related compounds that concentrate in bone, it was advisable to
      determine whether previous bisphosphonate administration has blocked subsequent
      uptake of Sm-153 EDTMP. The authors compared skeletal uptake of Sm-153 EDTMP
      before and 1 to 4 days after pamidronate infusion in three patients with breast
      cancer metastatic to bone. In two of the patients, they continued to compare Sm
      153 EDTMP uptake at approximately 1, 2, 3, and 4 weeks after pamidronate
      infusion. There was no difference in skeletal uptake of Sm-153 EDTMP before or at
      any time after pamidronate infusion. Pamidronate infusion did not interfere with
      skeletal uptake of Sm-153 EDTMP.

PMID- 12045436
TI  - Protein-losing enteropathy detected on Tc-99m HSA and Tc-99m MDP scintigraphy.
AB  - The authors describe a patient with protein-losing enteropathy in whom abnormal
      intestinal accumulation of tracer occurred during Tc-99m human serum albumin
      scintigraphy. Abnormal leakage of the radiotracer was observed in the left upper
      abdomen and was confirmed by Tc-99m MDP scintigraphy. Both Tc-99m HSA
      scintigraphy and Tc-99m MDP scintigraphy are useful in the detection of protein
      losing enteropathy.

PMID- 12045437
TI  - Regional cardiac sympathetic denervation and systolic compression of a septal
      perforator branch in a sudden death survivor with hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy is a heterogeneous primary cardiac disease with a
      broad clinical spectrum, including a high risk for sudden death in a certain
      subgroup of patients. However, the precise criteria for identifying the subgroup
      at high risk have not been established. The authors describe a 41-year-old man
      with hypertrophic cardiomyopathy who was examined after an episode of aborted
      sudden death. Extensive invasive and noninvasive investigations did not reveal a
      cardiac abnormality other than severe sympathetic denervation in the midbasal
      septal wall on iodine-123 MIBG SPECT imaging and concentric left ventricular
      hypertrophy on echocardiography. A retrospective review of the cardiac
      catheterization findings, however, revealed systolic compression of a septal
      perforator artery. The aborted sudden death of the patient was most likely
      associated with systolic compression of a septal branch or sympathetic
      denervation, which may have precipitated a ventricular arrhythmia in this
      patient.

PMID- 12045438
TI  - Symptomatic cortical desmoids detected on knee SPECT.

PMID- 12045439
TI  - Pathologic uptake in F-18 FDG positron emission tomography of the residuals of a
      surgically removed needle abscess.

PMID- 12045440
TI  - Wegener's granulomatosis causing main stem bronchial stenosis and large perfusion
      ventilation defects.

PMID- 12045441
TI  - Tc-99m MDP and Tc-99m MIBI dual imaging of photopenic bone metastases of
      carcinoma of the larynx.

PMID- 12045442
TI  - Aortic graft infection diagnosed on a Tc-99m HMPAO leukocyte scan.

PMID- 12045443
TI  - FDG positron emission tomographic imaging of pseudo-pseudo tumor.

PMID- 12045444
TI  - Contribution of an Anti-CEA Fab' scan in the detection of medullary thyroid
      cancer.

PMID- 12045445
TI  - Unusual localization of hydatid cyst: bone scintigraphy, brain SPECT, and
      magnetic resonance imaging Findings.

PMID- 12045446
TI  - Bone metastases from breast cancer localized to the pelvis.

PMID- 12045447
TI  - In-111 octreotide uptake in the thymus in a patient with Cushing's syndrome.

PMID- 12045448
TI  - A case of chylothorax diagnosed by lymphoscintigraphy using Tc-99m HSA-DTPA.

PMID- 12045449
TI  - Ga-67 scintigraphy in a patient with deep vein thrombosis as the probable cause
      of fever of unknown origin.

PMID- 12045450
TI  - Demonstration of peritonitis with Tc-99m (V) DMSA scintigraphy and negative
      results on Ga-67 scan.

PMID- 12045451
TI  - I-123 IMP pulmonary SPECT in a patient with acute pulmonary thromboembolism.

PMID- 12045452
TI  - Lick your lips: a case of salivary contamination after I-131 therapy for thyroid
      carcinoma.

PMID- 12045453
TI  - Massive ovarian cystadenoma detected solely on the blood-pool phase of a bone
      scan.

PMID- 12045454
TI  - A3 adenosine receptor as a target for cancer therapy.
AB  - Targeting the A3 adenosine receptor (A3AR) by adenosine or a synthetic agonist to
      this receptor (IB-MECA and Cl-IB-MECA) results in a differential effect on tumor
      and on normal cells. Both the adenosine and the agonists inhibit the growth of
      various tumor cell types such as melanoma, colon or prostate carcinoma and
      lymphoma. This effect is specific and is exerted on tumor cells only. Moreover,
      exposure of peripheral blood mononuclear cells to adenosine or the agonists leads
      to the induction of granulocyte colony stimulating factor (G-CSF) production.
      When given orally to mice, the agonists suppress the growth of melanoma, colon
      and prostate carcinoma in these animals, while inducing a myeloprotective effect
      via the induction of G-CSF production. The de-regulation of the Wnt signaling
      pathway was found to be involved in the anticancer effect. Receptor activation
      induces inhibition of adenylyl cyclase with a subsequent decrease in the level of
      protein kinase A and protein kinase B/Akt leading to activation of glycogen
      synthase kinase-3beta, a key element in the Wnt pathway. The oral bioavailability
      of the synthetic A3AR agonists, and their induced systemic anticancer and
      myeloprotective effect, renders them potentially useful in three different modes
      of treatment: as a stand-alone anticancer treatment, in combination with
      chemotherapy to enhance its therapeutic index and myelprotection. It is evident
      that use of the A3AR agonist for increasing the therapeutic index of chemotherapy
      may also invariably give rise to myeloprotection and vice versa. The A3AR
      agonists are thus a promising new class of agents for cancer therapy.

PMID- 12045455
TI  - Acronycine derivatives as promising antitumor agents.
AB  - Originally isolated from an Australian plant, acronycine is an antitumor alkaloid
      with poor water solubility and low potency. The modest antitumor activity of this
      compound was markedly improved by the total synthesis of original analogs
      resulting in the selection of S23906-1, a diester derivative of 1,2
      dihydrobenzo[b]acronycine. S23906-1 is characterized in vitro by a high potency
      in clonogenic assays and uncommon cell cycle pertubations. In vivo, this compound
      demonstrated a selectivity for human solid tumors as compared to murine
      transplantable tumors. The unique pharmacological profile of S23906-1 was
      particularly defined by a broad antitumor efficacy when administered i.v. or
      orally on aggressive orthotopic models of human lung, ovarian and colon models
      with comparable or better activity than clinically used anticancer drugs. The
      molecular mechanism of action of S23906-1 could involve DNA alkylation,
      modulation of cyclin E protein levels and inhibition of DNA synthesis leading to
      apoptosis. Ongoing preclinical toxicological studies will help to define the
      potential of this novel agent which is already considered as a valuable candidate
      for clinical studies.

PMID- 12045456
TI  - Docetaxel in advanced gastric cancer.
AB  - Standard chemotherapy for advanced gastric cancer remains undefined. Two of the
      most popular regimens-ECF [epirubicin-cisplatin-5-fluorouracil (5-FU)] and PELF
      (cisplatin-epirubicin-5-FU-leucovorin)-have been shown to be active, but each has
      limitations. Phase II trials show that single-agent docetaxel is an active agent
      in advanced gastric cancer, producing overall response rates (ORRs) of 17.5-24%.
      Docetaxel has also been shown to lack cross-resistance with other drugs in
      gastric cancer, and is likely to be at least additive to cisplatin and 5-FU.
      Phase II results of docetaxel combinations in advanced gastric cancer are
      encouraging. Docetaxel-cisplatin has yielded response rates similar to those
      achieved by ECF and PELF. Adding 5-FU to docetaxel-cisplatin has achieved an ORR
      of 52 versus 45% for docetaxel-cisplatin in a randomized phase II trial.
      Docetaxel-based regimens demonstrate acceptable tolerability despite predictable
      hematotoxicity. Neutropenia, the major toxicity, is manageable by dose
      modification or by using prophylactic granulocyte colony stimulating factor.
      Several phase III trials are now ongoing, including a large-scale trial of
      docetaxel-cisplatin-5-FU versus cisplatin-5-FU. Results will show whether
      docetaxel improves overall response and survival, as suggested in the phase II
      setting.

PMID- 12045457
TI  - Advanced colorectal cancer treatment in Europe: what have we achieved?
AB  - The goal of the present paper is to review how treatment of advanced colorectal
      cancer has evolved during the last 10 years and to make some suggestions on how
      that disease could be managed today. 5-Fluorouracil (5-FU) combined with folinic
      acid (FA) remains the basis for advanced colorectal cancer treatment. In Europe,
      infusional 5-FU is considered to be more active and better tolerated than bolus 5
      FU. New agents including oral 5-FU prodrugs UFT/FA, and capecitabine, tomudex,
      irinotecan and oxaliplatin have been shown active in advanced colorectal cancer.
      At presentation the combination of infusional 5-FU/FA with irinotecan or
      oxaliplatin is considered to be superior to any of these agents used alone,
      yielding a median survival of up to 16-19 months. Second-line therapy could
      further prolong survival in selected patient populations. Eventually chemotherapy
      could allow curative resection of previously unresectable hepatic and pulmonary
      metastases.

PMID- 12045458
TI  - A limited-sampling strategy to estimate individual pharmacokinetic parameters of
      vinorelbine in elderly patients with advanced metastatic cancer.
AB  - The aim of this study was to characterize the population pharmacokinetic of
      vinorelbine in elderly patients and to propose a limited-sampling strategy to
      estimate individual pharmacokinetic parameters. Vinorelbine was administered by a
      10-min continuous infusion at a dose of 20-30 mg/m2. The population parameters
      were computed, using a three-compartment model, from an initial group of 27
      patients. Twelve additional courses were used for model validation and evaluation
      of eight different limited-sampling strategies. The inter-individual variability
      of CL was explained by a linear dependency with age. The population average
      parameters and the interindividual variabilities (CV%) were: CL=47.1 l/h (31.7%),
      V=16.6 l (64%), k21=0.776 h-1 (20%), k31=0.0346 h-1 (15.2%), alpha=0.431 h-1
      (6.84%) and beta=0.0167 h-1 (25%). Bayesian estimation with three measured levels
      (end of infusion, and 6 and 48 h) can be selected, because it allows adequate
      estimation of CL, elimination half-life and vinorelbine concentrations with a non
      significant bias. Moreover, the choice of these three sampling times presents
      practicality advantages for the patient's comfort. Vinorelbine clearance
      decreasing with age and AUC being a good predictor of several toxicity end points
      during vinorelbine treatment, the limited-sampling strategy developed in this
      paper may be clinically relevant.

PMID- 12045459
TI  - Pharmacodynamics of non-break weekly paclitaxel (Taxol) and pharmacokinetics of
      Cremophor-EL vehicle: results of a dose-escalation study.
AB  - We characterized the toxicity and determined the maximum tolerated dose of non
      break weekly paclitaxel (Taxol) in chemotherapy-naive cancer patients, and
      studied pharmacokinetics of the formulation vehicle Cremophor-EL with this
      schedule. Twenty-three patients with primary refractory solid tumors received
      weekly paclitaxel at the dose range of 70-200 mg/m2. As dose-limiting toxicity we
      defined granulocytopenia grade > or =2 causing a treatment delay for more than 2
      weeks, or febrile neutropenia or grade >2 organ-specific toxicity. Plasma
      kinetics of Cremophor-EL were analyzed over the first five courses of treatment.
      Non-break weekly paclitaxel was feasible at doses up to 110 mg/m2, while
      granulocytopenia precluded scheduled administration of doses > or =130 mg/m2.
      Clinically relevant peripheral neurotoxicity tended to occur at around 1500 mg/m2
      cumulative dosage at weekly doses > or =110 mg/m2. Detectable Cremophor-EL levels
      were found in all pre-dose samples, but there was no evidence of accumulation up
      to the sixth course. Our results, discussed in the light of an overview of
      published data, suggest that chronic weekly administration of paclitaxel is
      feasible and with a lack of significant accumulation of Cremophor-EL levels at
      doses up to 90 mg/m2.

PMID- 12045460
TI  - Mitoxantrone and cisplatin in recurrent and/or metastatic salivary gland
      malignancies.
AB  - A phase II study was performed to assess the safety and efficacy of mitoxantrone
      and cisplatin in locally recurrent and/or metastatic carcinomas of the salivary
      glands. Between May 1997 and March 2001, a total of 14 patients were entered on
      this trial. All of them had previously undergone radical resection and 10 were
      subsequently treated with adjuvant radiation therapy with (n=3) or without (n=7)
      concomitant chemotherapy. Therapy according to the study protocol consisted of
      mitoxantrone given as i.v. bolus on day 1 at a dose of 12 mg/m2 and cisplatin
      given as 90-min infusion at a dose of 30 mg/m2 on days 1-3. We observed two
      partial responses (14.3%) and stabilization of disease in nine patients (64.3%);
      progression during therapy was noted in only three cases (21.4%). The median time
      to progression was 15 months (range 2-36) and the median survival time was 27
      months (range 4-54). Myelosuppression was commonly observed. Leukocytopenia
      occurred in all patients, and was grade 3 or 4 in three (21%) and four (29%)
      patients. WHO grade 3 thrombocytopenia and anemia was seen in three (21%) and
      four (29%) patients, respectively. Non-hematologic toxicity was in general mild
      to moderate except for two cases (14%) of grade 3 nausea and vomiting; overall
      incidence rates were nausea and vomiting (n=14), stomatitis (n=6), diarrhea
      (n=3), alopecia (n=11), infection (n=7), increase of serum creatinine (n=3), and
      peripheral neuropathy (n=3). The combination of mitoxantrone and cisplatin seems
      to be an active and fairly well-tolerated regimen for the treatment of advanced
      salivary gland cancers. According to the observed high rate of abrogating
      progressive disease for a long duration, and the resulting promising progression
      free and overall survival time, further investigation seems warranted.

PMID- 12045461
TI  - Phase II study of weekly paclitaxel plus 24-h continuous infusion 5-fluorouracil,
      folinic acid and 3-weekly cisplatin for the treatment of patients with advanced
      gastric cancer.
AB  - The aim of this study was to evaluate the toxicity and efficacy of combination
      chemotherapy with weekly 24-h continuous infusion of 5-fluorouracil (5
      FU)/folinic acid, weekly paclitaxel and 3-weekly cisplatin in patients with
      unresectable, locally advanced or metastatic gastric adenocarcinoma. Between
      November 1999 and November 2001, 29 chemotherapy-naive patients (13 male and 16
      female) with a median age of 56 years (range 22-72) were consecutively enrolled
      at three centers. 5-FU 2 g/m2 was given weekly over 24 h i.v. preceded by folinic
      acid 500 mg/m2 as a 2-h infusion. Paclitaxel 80 mg/m2 was administered as a 1-h
      infusion weekly and cisplatin 50 mg/m2 as 1-h infusion on days 8 and 29. Six
      weeks of therapy (days 1, 8, 15, 22, 29 and 36) followed by 1 week of rest was
      considered one cycle. A median of 3 cycles (range 1-5) was administered to 29
      patients with a total of 73 cycles applied. All patients were assessable for
      toxicity and survival, 28 patients were assessable for response (one patient
      received less than one complete cycle and could not be evaluated for response).
      Four patients (14%) obtained a complete response and 10 patients (34%) a partial
      response (overall response rate 48%, 95% CI 29-68%). Seven patients (24%) had
      stable disease. Seven patients (24%) had progressive disease during or within 4
      weeks after treatment. The median progression-free and overall survival times
      were 8 months (range 1-23) and 11 months (range 1-23), respectively. Overall
      toxicity was acceptable. Hematological toxicity was favorable with only one
      patient (3%) experiencing WHO grade 3/4 leukocytopenia and one patient (3%) WHO
      grade 3/4 anemia. Non-hematologic WHO grade 3/4 toxicities included alopecia in
      19 (66%), nausea/vomiting in six (21%), diarrhea in six (21%), neurotoxicity
      grade 3 in three (10%) and infection in three (10%) patients. A total of 42
      applications (10%) (range 0-5) had to be postponed and dose reductions of at
      least one drug was necessary in 37% of applications. In three patients (10%)
      treatment was stopped because of toxicity. All patients were treated on an
      outpatient basis. Thus, the combination of weekly paclitaxel, cisplatin and
      continuously infused 5-FU/folinic acid appears to be a highly active regimen for
      the treatment of patients with advanced gastric cancer. Compared with our
      previous experience with the same combination of drugs but using paclitaxel at
      175 mg/m2 given every 3 weeks, the protocol with weekly application of paclitaxel
      80 mg/m2 shows a reduced incidence of hematologic toxicity, particularly
      leukopenia. Other organ toxicities apart from a slightly higher incidence of
      peripheral neuropathy were comparable between the two treatment protocols.
      Efficacy with a response rate of 50% was well preserved by this weekly regimen.

PMID- 12045462
TI  - Phase I study of carboplatin, irinotecan and docetaxel on a divided schedule with
      recombinant human granulocyte colony stimulating factor support in patients with
      stage IIIB or IV non-small cell lung cancer.
AB  - A phase I study was conducted to determine dose-limiting toxicity (DLT) and
      maximum tolerated dose (MTD) of carboplatin combined with irinotecan and
      docetaxel on a divided schedule with recombinant human granulocyte colony
      stimulating factor (rhG-CSF) support in patients with stage IIIB or IV non-small
      cell lung cancer. Carboplatin was given at the dose of AUC5 on day 1. Irinotecan
      and docetaxel on days 1 and 8 were administered at a starting dose of 40 and 30
      mg/m2 as level 1. Subsequent levels were: irinotecan/docetaxel (in mg/m2), 50/30
      (level 2), 60/30 (level 3) and 60/35 (level 4). rhG-CSF was given at 50 mg/m2 on
      days 5-15. Cycles were repeated every 3 weeks. Between May 1999 and April 2001,
      31 patients were registered in this phase I study. Level 4 was judged as the MTD.
      The DLTs were considered diarrhea and febrile neutropenia. The overall response
      rate was 32.3% and median survival was 490 days with 1-year survival of 65.1%. We
      conclude that both irinotecan 60 mg/m2 and docetaxel 30 mg/m2 on days 1 and 8 in
      combination with an AUC5 of carboplatin on day 1 with rhG-CSF support is
      recommended for phase II study. The response rate and survival data in this phase
      I study are encouraging. We considered that the pathogenesis of diarrhea involved
      not only direct cytotoxic damage to the mucosa, but also bacterial overgrowth.

PMID- 12045463
TI  - DNA repair protein levels vis-a-vis anticancer drug resistance in the human tumor
      cell lines of the National Cancer Institute drug screening program.
AB  - Nucleotide excision repair (NER) is a multi-enzyme DNA repair pathway in
      eukaryotes. Several NER genes in this pathway including XPB, XPD, XPA and ERCC-1
      have been implicated in anticancer drug resistance in human tumor cells. In this
      study, we assessed the levels of the above-mentioned proteins in the NCI panel of
      60 human tumor cell lines in relation to the cytotoxicity patterns of 170
      compounds that constitute the standard agent (SA) database. The database consists
      of drugs used in the clinic for which a mechanism of action has been at least
      partially defined. The ERCC-1, XPD and XPB protein expression patterns yielded
      significant negative Pearson correlations with 13, 32 and 17 out of the 170
      compounds, respectively (using p<0.05). XPA produced a random assortment of
      negative and positive correlations, and did not appear to confer an overall
      resistance or sensitivity to these drugs. Protein expression was also compared
      with a pre-defined categorization of the standard agents into six mechanism-of
      action groups resulting in an inverse association between XPD and alkylating
      agent sensitivity. Our present data demonstrate that XPD protein levels correlate
      with resistance to alkylating agents in human tumor cell lines suggesting that
      XPD is implicated in the development of this resistance. NER activity, using the
      in vitro cell-free system repair assay, revealed no correlation between NER
      activity and the level of XPD protein in four cell lines with widely varying XPD
      protein levels. This lack of correlation may be due to the contribution of XPD to
      other functions including interactions with the Rad51 repair pathway.

PMID- 12045464
TI  - Effects of tamoxifen on human squamous cell carcinoma lines of the head and neck.
AB  - Tamoxifen (TAM) is a well-tolerated compound in the treatment of breast cancer
      and is primarily considered to act by competition with estrogen receptors (ER).
      Here we investigated the in vitro efficacy and potentially underlying mechanisms
      of TAM in established cell lines of squamous cell carcinomas of the head and neck
      (SCCHN). Using proliferation and apoptosis assays the antitumor activity of TAM
      in five SCCHN and the breast carcinoma line MCF-7 (positive control) was
      determined. MCF-7 was more sensitive to low-dose TAM (below 1 microM), whereas
      SCCHN showed significant growth inhibition at higher TAM concentrations (5-10
      microM). Growth curve analysis and apoptosis assays were indicative for a
      cytostatic effect of low-dose TAM and high-dose TAM led to cell loss by apoptosis
      in sensitive SCCHN. In order to further characterize the observed antitumor
      effects we determined the amount of steroid hormone receptors with the dextran
      coated charcoal method and immunocytochemistry. In addition, production of
      transforming growth factor (TGF-)-alpha, -beta1 and -beta2 was measured by ELISA,
      and protein kinase C (PKC) activity was assessed with a radioligand assay. Except
      MCF-7, none of the SCCHN lines was positive for ER. TAM caused decreased TGF
      alpha and increased TGF-beta levels in MCF-7, but not in SCCHN supernatants.
      Furthermore, the antiestrogen reduced PKC activity in MCF-7, but not in SCCHN. In
      the present in vitro system, the observed antitumor activity of high-dose TAM in
      SCCHN cannot be explained by estrogen antagonism, alterations of TGF-alpha/beta
      levels or decreased PKC activity.

PMID- 12045465
TI  - Dimethyladamantylmaleimide-induced in vitro and in vivo growth inhibition of
      human colon cancer Colo205 cells.
AB  - The effect of N-1-(3,5-dimethyladamantyl)maleimide (DMAMI) on the growth of
      Colo205 human colon cancer cells was examined both in vitro and in vivo. Flow
      cytometry analysis showed a decrease of G2/M Colo205 cells at 4-6 h after
      treatment with DMAMI prior to accumulation of apoptotic cells at 24 h.
      Significant changes in cell morphology, i.e. shrinkage and chromatin condensation
      of cells, were observed after treatment with DMAMI. In the analysis of the
      apoptosis markers, it was found that the increase of Annexin V binding to
      membrane, peroxide radicals, dissipation of the mitochondrial membrane potential,
      and the activation of caspase-3, -8 and -9 were all evident at 4-6 h after
      treatment with DMAMI. In vivo analysis showed that treatment of Colo205 tumor
      bearing SCID mice with DMAMI (230 mg/kg, intratumoral, once) resulted in rapid
      tumor damage that leads to significant tumor growth inhibition and no obvious
      acute toxicity. These results suggest that DMAMI has potential for local
      treatment of cancer.

PMID- 12045466
TI  - Forward, relaxed, and reverse selection for reduced and enhanced sensitivity to
      ethanol's locomotor stimulant effects in mice.
AB  - BACKGROUND: Rarely have trait markers for alcoholism risk been identified.
      However, relative sensitivity to the arousing effects of ethanol and sensitivity
      to ethanol's sedative effects have been distinguished as potentially valuable
      behavioral risk factors. Both traits are genetically influenced and have been
      modeled in mice by measuring sensitivity to ethanol-induced locomotor stimulation
      and hypnosis. Reverse selection was performed to examine the hypothesis that
      forward selection for differential sensitivity to ethanol's locomotor stimulant
      effects resulted in homozygous fixation of selection trait-relevant alleles and
      to test the hypothesis that common genes influence ethanol's stimulant and
      sedative effects. METHODS: Bidirectional selective breeding was completed for
      enhanced (FAST mice) and reduced (SLOW mice) sensitivity to ethanol's locomotor
      stimulant effects. Selection was terminated (relaxed), and the lines were tested
      to detect genetic drift. Reverse selection for enhanced sensitivity to ethanol
      induced stimulation in SLOW mice and reduced sensitivity in FAST mice was
      performed for 16 generations. Forward and reverse selected lines were tested for
      sensitivity to ethanol's sedative effects by measuring duration of ethanol
      induced loss of righting reflex. RESULTS: Differential sensitivity to the
      sedative effects of ethanol emerged with selection for differential ethanol
      stimulation, indicating a common genetic influence on these traits. SLOW mice
      developed greater sensitivity to ethanol's sedative effects relative to FAST
      mice. Reverse selection, never before reported for a pharmacogenetic trait, was
      effective in eliminating most of the difference in stimulant sensitivity between
      the FAST and SLOW lines and also eliminated the difference in loss of righting
      reflex duration. CONCLUSIONS: Residual heterozygosity persisted at trait-relevant
      loci even at the selection plateau, possibly due to heterosis, natural selection
      favoring heterozygosity, or epistatic phenomena involving differences in the sets
      of genes regulating the high- versus low-sensitivity traits. They also suggest
      that some common genes influence sensitivity to ethanol's locomotor stimulant and
      sedative effects.

PMID- 12045467
TI  - Linkage for platelet monoamine oxidase (MAO) activity: results from a replication
      sample.
AB  - BACKGROUND: Monoamine oxidase B (MAO-B) degrades catecholamines in presynaptic
      nerve endings and is also active in platelets. There is evidence to suggest that
      platelet MAO-B activity level is controlled by a major genetic locus distinct
      from the structural gene on the X chromosome. To expand on a prior report, new
      linkage analyses for platelet MAO-B activity have been performed on the
      previously analyzed sample (designated the initial sample), on a new sample of
      families (the replication sample), and on the combined sample. These families
      were recruited as part of the Collaborative Study on the Genetics of Alcoholism
      (COGA). METHODS: The initial sample consists of 105 extended families providing
      1002 nonindependent (412 independent) sib pairs that have been phenotyped for MAO
      activity and genotyped. The replication sample of 157 extended families contains
      608 nonindependent (309 independent) phenotyped and genotyped sib pairs. Analyses
      were conducted using Haseman-Elston based regression on sib pairs and variance
      component analysis on extended pedigrees, and the importance of cigarette smoking
      and gender as covariates of platelet MAO-B activity was taken into account.
      RESULTS: Regions on chromosomes 2, 9, and 12 indicated consistent evidence for
      linkage across the two distinct datasets by at least one analysis method. Under
      Haseman-Elston regression of independent sib pairs, only the chromosome 2 region
      gave lod scores above 1 in both the initial and replication samples. Using all
      possible pairs, unweighted, for the regression, chromosome 12 gave lod scores
      above 1 in both samples. For variance component analysis, only the chromosome 9
      region gave lod scores above 1 in both samples. CONCLUSIONS: The consistency
      across datasets of these findings is encouraging. In particular, variance
      component analysis of extended pedigrees supports a potential linkage of MAO-B
      activity to chromosome 9, with a lod over 3 at 115 cM near D9S261 in the combined
      sample. Sib-pair regression supports this finding with modest lod scores in the
      region. Suggestive linkage to chromosomes 2 and 12 from sib-pair analysis is only
      weakly supported by variance component analysis.

PMID- 12045468
TI  - Mapping of quantitative trait loci underlying ethanol metabolism in BXD
      recombinant inbred mouse strains.
AB  - BACKGROUND: Genetic factors are well known to play an important role in
      determining individual differences in the metabolism of ethanol (EtOH), and
      several specific polymorphic loci have been identified that significantly
      contribute to the variability of EtOH metabolism in humans. However, these
      variant genes are either alcohol or aldehyde dehydrogenases, and the
      identification of new gene products that contribute to variation in alcohol
      metabolism would be useful. METHODS: To identify quantitative trait loci (QTLs),
      we correlated variation in polymorphic markers with blood EtOH concentration and
      the rate of EtOH metabolism (beta) in C57BL/6J and DBA/2J strains and in 25 of
      their recombinant inbred strains after 2 and 3 g/kg of EtOH intraperitoneally.
      RESULTS: A QTL associated with beta values for both doses was definitively mapped
      to the proximal region of chromosome 17, syntenic with human chromosome 6q25-27.
      Seven to 12 chromosomal regions were provisionally identified for each phenotype;
      several were associated with 2 or more phenotypes. Each QTL suggests the location
      of a gene or genes affecting EtOH pharmacokinetics. Candidate genes suggested by
      these analyses included several whose gene products are known to be induced by
      EtOH (e.g., superoxide dismutase, glutathione transferase, and cytochrome P450
      2E1), as well as several whose gene products have signaling functions likely to
      contribute to this induction. CONCLUSIONS: These studies provide evidence for the
      existence of genes affecting EtOH metabolism in multiple chromosomal regions.
      Future studies will be required to identify the chromosome 17 gene product. Use
      of other genetic populations, such as B6D2F2 crosses, will be required to
      determine which of the provisional loci represent true and which represent false
      positive associations.

PMID- 12045469
TI  - Alcohol consumption promotes body weight loss in melanoma-bearing mice.
AB  - BACKGROUND: Alcohol consumption is an important risk factor for cancer. Little is
      known about its effects on cancer progression. Previously, we showed that high
      ethanol consumption inhibited metastasis of B16BL6 melanoma-bearing mice without
      affecting primary tumor growth. On the other hand, ethanol-consuming tumor
      bearing (TE) mice exhibited decreased survival and decreased body weight as
      compared to water-drinking, tumor-bearing (TW) mice. The focus of this study was
      to determine how alcohol promotes weight loss in melanoma-bearing mice. METHODS:
      Female, C57BL/6 mice were given water or 20% w/v ethanol in the drinking water
      for 3 weeks to 6 months before subcutaneous inoculation of 1 x 10(6) B16BL6
      melanoma cells. Mice continued to receive the same fluids. Biochemical parameters
      were evaluated at various times after tumor inoculation. Body weight, water
      content, tumor weight and carcass fat content were determined at necropsy.
      RESULTS: TW mice elicted a modest weight loss. This response was magnified 2-fold
      by alcohol consumption. The weight loss in TE mice is not caused by dehydration,
      decreased energy intake, or loss of skeletal muscle mass. It resulted
      specifically from loss in body fat. Other alterations associated with the fat
      loss in TE mice were: (1) decreased glucose, (2) elevated fatty acids, (3)
      elevated beta-hydroxybutyrate, (4) elevated glucagon, and (5) increased leptin
      levels in plasma. Body temperature decreased about 2.9 degrees C in TE mice.
      Metabolic rate increased in TW mice. The fat loss due to alcohol consumption in
      tumor-bearing mice was not due to increased metabolic rate. CONCLUSIONS: The
      response elicited by alcohol consumption in tumor-bearing mice is complex and
      associated with alterations in metabolism and hormones. These findings suggest
      that alcohol abuse could be a risk factor for cancer patients because it invokes
      a strong depletion of body fat. This could facilitate wasting and shorten
      survival time.

PMID- 12045470
TI  - Videotaped cue for urge to drink alcohol.
AB  - BACKGROUND: The urge to drink alcohol can be robustly and reliably induced via
      actual exposure to a person's preferred alcoholic beverage. Unfortunately, these
      exposure paradigms are unwieldy for functional magnetic resonance imaging
      studies. The goal of this study was to examine whether viewing a personalized
      videotaped cue could induce alcohol craving. The following hypotheses were
      tested: (1) individualized cue videotapes can reliably elicit the urge to drink
      alcohol in alcohol-dependent participants and (2) alcohol drinking histories can
      predict reactivity to cue. METHODS: DSM-IV criteria were used to identify an
      alcohol-dependent group (ADG). Controls included a light-drinking group and a
      moderate-drinking group. Urge to drink alcohol was assessed at baseline and after
      each of five in vivo exposure conditions: water (W), alcohol 1 (A1), mood
      induction (M), alcohol 2 (A2), and relaxation (R). The entire exposure session
      was videotaped. Each participant's video footage was digitally edited to produce
      a 17.5-min cue that was presented to the participant 24 to 72 hr later. Ratings
      of urge to drink alcohol across the five exposure conditions were compared for
      both the in vivo and the video exposure sessions. RESULTS: Fourteen participants
      (five in the light-drinking group, four in the moderate-drinking group, and five
      in the ADG) completed both sessions. Participants in each group showed
      differences between neutral cue exposure (W and R) and alcohol-related cue
      exposure (A1, M, and A2) in both the in vivo cue session (p < 0.002) and the
      videotape session (p < 0.02). Post hoc comparisons among the groups to alcohol
      related cues established that, in both sessions (p(in vivo) = 0.04; p(videotape)
      = 0.04), the ADG demonstrated the greatest urge to drink. CONCLUSIONS: Alcohol
      cue reactivity can be reliably induced and assessed in alcohol-dependent
      participants via personalized videotapes. History of alcohol consumption is
      positively correlated with the degree of cue reactivity. This study advances our
      ability to assess alcohol cue reactivity in the absence of alcohol.

PMID- 12045471
TI  - Microanalysis of ethanol self-administration: estrous cycle phase-related changes
      in consumption patterns.
AB  - BACKGROUND: Female rodent and reproductive cycle-related patterns in ethanol
      consumption have been identified grossly, but the regulatory processes that
      underlie these patterns remain to be clarified. The evaluation of consummatory
      bout dynamics may be useful in determining the effects of a changing endogenous
      state (ovarian hormone fluctuations) on ethanol consumption patterns. This study
      assessed the microstructural components of ethanol intake patterns across the
      estrus cycle. METHODS: Cumulative licking of 13 female Long-Evans rats was
      recorded during continuous access (22 hr/day) to 10% ethanol and tap water
      solutions throughout a 10 week period. Drinking bouts were defined as 20 or more
      successive licks separated by less than a 60 sec pause. Vaginal smears were
      obtained daily from each rat between 1100 and 1130 hr to assess estrus cycle
      phase. ANOVAs were conducted to evaluate estrus cycle effects on consumption
      pattern parameters. RESULTS: Total daily ethanol intakes were unaffected by
      estrus cycle phase. Ethanol bout frequency was significantly greater during
      proestrus compared with all other phases, whereas ethanol bout sizes were
      significantly attenuated during proestrus compared with estrus and diestrus.
      Experience with ethanol was associated with a significant decline in bout
      frequency and a significant elevation in bout size across all cycle phases, which
      indicated that initiation of ethanol self-administration occurred over time. A
      significant main effect of hour and a cycle phase by hour interaction were found
      for the temporal distribution of ethanol lick responses throughout the estrus
      cycle, and a progressive shift in lick patterns evolved between estrus and the
      subsequent proestrus. CONCLUSIONS: The estrus cycle phase-related changes in the
      microstructural components of ethanol intake suggest that female rats experience
      periods of altered sensitivity to the neurobiological and reinforcing effects of
      ethanol. Furthermore, these findings implicate cyclical fluctuations in ovarian
      hormones and other neuromodulators in the regulation of ethanol consumption
      patterns throughout the estrus cycle of the female rat.

PMID- 12045472
TI  - Early responsiveness to stimuli paired with different stages within the state of
      alcohol intoxication.
AB  - BACKGROUND: Infant rats quickly learn to avoid a sensory cue paired with alcohol
      as an unconditioned stimulus, particularly when the drug reaches peak blood
      concentrations. In this study, a tactile cue paired with the onset of alcohol
      intoxication preceded subsequent presentations of a gustatory conditioned
      stimulus (CS). The goal was to address the possibility of differential
      conditioning depending on when stimuli were introduced during the course of the
      toxic state. METHODS: In experiment 1, rat pups received sequential presentations
      of a salient texture (sandpaper) and a gustatory cue (saccharin) while
      intoxicated with a 2.5 g/kg alcohol dose or after receiving saline. Texture
      location tests and saccharin intake assessments were then performed. A third
      modality of assessment was defined by a saccharin intake test while pups
      simultaneously experienced sandpaper. In experiment 2, alcohol-mediated
      conditioning was followed by tests similar to those of experiment 1, but after
      pups were re-exposed to either the tactile CS or the alcohol-unconditioned
      stimulus. RESULTS: Conditioned taste aversions, due to pairing saccharin and the
      later stage of alcohol intoxication, were reliably established in both
      experiments. Also in both experiments, this excitatory aversive response was
      dramatically inhibited when the association between the texture CS and the
      earlier stage of alcohol intoxication was activated. There were no indications of
      conditioned motor responses to the tactile CS that might compete with intake
      behavior of saccharin or distort measurement of an appetitive memory derived from
      pairing the texture and the earlier stage of intoxication. CONCLUSIONS: Rat pups'
      expression of an association between a taste signaling aversive consequences of
      alcohol was eliminated by the presence of a tactile stimulus that originally had
      signaled the absence of aversive consequences of alcohol intoxication. The
      results suggest the interaction of inhibitory and excitatory conditioning
      involving the aversive properties of alcohol.

PMID- 12045473
TI  - Acamprosate has no effect on NMDA-induced toxicity but reduces toxicity induced
      by spermidine or by changing the medium in organotypic hippocampal slice cultures
      from rat.
AB  - BACKGROUND: It has been suggested that the antirelapse drug acamprosate can
      inhibit or potentiate glutamate/NMDA receptor-mediated responses via a polyamine
      site. Additionally, subchronic exposure to acamprosate increases expression of
      some NMDA receptor subunits. These effects on NMDA receptors imply that the drug
      may have neurotoxic or neuroprotective actions under different conditions, and
      these studies were undertaken to evaluate this possibility in hippocampal
      neuronal cultures. METHODS: Organotypic hippocampal cultures from 8-day-old
      neonatal rats were maintained in medium for 28 days. The effects of acamprosate
      (100 microM) alone or on neurotoxic challenges induced by either 50 microM NMDA
      or 100 microM spermidine were studied. Neurotoxicity was assessed by uptake of
      propidium iodide 24 hr after challenge. Calcium entry was measured by uptake of
      45Ca2+ into the culture during the challenge. RESULTS: Acamprosate produced no
      neurotoxicity in these cultures after acute or subchronic exposure. In contrast,
      the presence of acamprosate significantly reduced "basal" propidium iodide uptake
      caused by the medium change procedure; similar effects were obtained with
      dizocilpine (MK-801; 30 microM) and, to a lesser extent, with ifenprodil (50
      microM). Acamprosate did not significantly potentiate or inhibit NMDA-induced
      neurotoxicity, but the presence of acamprosate significantly reduced spermidine
      induced neurotoxicity. CONCLUSION: No evidence was obtained that the putative
      agonist or coagonist effects of acamprosate on the NMDA receptor are able to
      cause neurotoxicity. Similarly, no evidence for inhibitory effects of acamprosate
      on NMDA-induced toxicity was observed under any of these conditions. However,
      acamprosate significantly inhibited the toxicity associated with changing medium
      and the toxicity induced by spermidine in these hippocampal cultures. The
      mechanism is unknown but is compatible with previously reported inhibition of
      polyamine-mediated effects.

PMID- 12045474
TI  - Impairment of neuronal nitric oxide synthase-dependent dilation of cerebral
      arterioles during chronic alcohol consumption.
AB  - BACKGROUND: Although chronic alcohol consumption impairs endothelial nitric oxide
      synthase-dependent reactivity of cerebral arterioles, the effect of alcohol
      consumption on vasodilation in response to activation of neuronal nitric oxide
      synthase (nNOS) has not been examined. Thus, our first goal was to determine
      whether chronic alcohol consumption impairs nNOS-dependent reactivity of pial
      arterioles. Our second goal was to examine potential mechanisms for impaired
      responses of pial arterioles during chronic alcohol consumption. METHODS: Sprague
      Dawley rats were fed liquid diets with or without alcohol for 8 to 12 weeks. By
      using intravital microscopy, we measured the diameter of pial arterioles in
      response to nNOS-dependent agonists--NMDA and kainate (KA)--in the absence and
      presence of N(G)-monomethyl-L-arginine (L-NMMA) or 7-nitroindazole (7-NI). We
      also measured responses of pial arterioles to nitroglycerin. Next, using Western
      blot analysis, we measured protein levels of the NMDA receptor subunit, KA
      receptor subunit, and nNOS protein in cerebral microvessels, parietal cortex,
      cerebellum, and brainstem of non-alcohol-fed and alcohol-fed rats. RESULTS:
      Topical application of NMDA (100 and 300 microM) and KA (100 and 300 microM)
      produced dose-related dilation of pial arterioles in non-alcohol-fed and alcohol
      fed rats. However, the magnitude of vasodilation in response to NMDA and KA, but
      not nitroglycerin, was significantly less in alcohol-fed compared with non
      alcohol-fed rats. Topical application of L-NMMA (10 microM) or 7-NI (10 microM)
      significantly inhibited dilation of pial arterioles in response to NMDA and KA in
      non-alcohol-fed rats. In alcohol-fed rats, only NMDA-induced vasodilation was
      inhibited by L-NMMA. In addition, we found that NMDA receptor subunit and KA
      receptor subunit protein levels increased in the parietal cortex and cerebellum
      of alcohol-fed compared with non-alcohol-fed rats. However, no significant
      difference in protein level of nNOS was observed between non-alcohol-fed and
      alcohol-fed rats. CONCLUSIONS: Our findings suggest that chronic alcohol
      consumption impairs nNOS-dependent dilation of pial arterioles via a mechanism
      that appears to be unrelated to quantitative changes in NMDA receptors, KA
      receptors, or nNOS. Because the regulation of cerebral blood flow is influenced
      by neuronal activation, impaired reactivity of cerebral blood vessels to neuronal
      activation may contribute to the pathogenesis of cerebrovascular disorders
      observed during chronic alcohol consumption.

PMID- 12045475
TI  - Effects of ethanol and basic fibroblast growth factor on the transforming growth
      factor beta1 regulated proliferation of cortical astrocytes and C6 astrocytoma
      cells.
AB  - BACKGROUND: The effects of ethanol on transforming growth factor beta1 (TGFbeta1)
      regulated proliferation of primary cultured cortical astrocytes and C6
      astrocytoma cells were determined. METHODS: Cultured cells were treated with
      TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for as many as 4 days. The
      effects of these treatments on cell growth (the change in cell number) and cell
      proliferation (incorporation of [3H]thymidine) were determined. In addition, the
      effects of serum and basic fibroblast growth factor (bFGF) on TGFbeta1-affected
      cell proliferation were examined. RESULTS: Both TGFbeta1 and ethanol inhibited
      cell growth and proliferation among the two types of cells; this effect was only
      evident when the cells were grown in the presence of a mitogen, serum, or bFGF.
      When added together (either in a serum-supplemented or serum-free medium),
      however, TGFbeta1 and the mitogen effectively nullified each other. TGFbeta1
      blocked the mitogenic effect of bFGF on astrocytes and C6 cells. Ethanol did not
      affect (i.e., neither added nor nullified) this antagonistic effect. CONCLUSIONS:
      TGFbeta1, like ethanol, is a potent anti-proliferative agent; either can nullify
      the mitogenic activity of serum or bFGF. Astrocytes and astrocyte-like cells
      react to combined TGFbeta1 and ethanol treatment differently than do neurons for
      which the inhibitory effects of TGFbeta1 and ethanol are additive.

PMID- 12045476
TI  - Beer congener stimulates gastrointestinal motility via the muscarinic
      acetylcholine receptors.
AB  - BACKGROUND: Ethanol and alcoholic beverages are known to affect upper
      gastrointestinal motility in humans. Beer has been reported to accelerate gastric
      emptying compared with other beverages that contain the same ethanol
      concentrations. In this study, we investigated the mechanism that underlies the
      effects of beer congener on gastrointestinal motility. METHODS: Gastric emptying
      activity was measured by means of movement of a semisolid test meal (0.05% phenol
      red/1.5% methylcellulose) in mice. To elucidate the mechanism for the effect of
      beer congener on gastrointestinal motility, we conducted receptor binding assays
      and contraction study by using longitudinal muscle from guinea pig ileum.
      RESULTS: Beer congener (1 g/kg orally) enhanced gastric emptying of a semisolid
      meal in mice. The receptor binding assay revealed that beer congener bound to
      dopamine D2 receptor and 5-hydroxytryptamine (5-HT)3 receptor. These IC50 values
      were more than 5 mg/ml. However, beer congener bound to 5-HT2 receptor, 5-HT4
      receptor, and muscarinic M3 receptor with IC50 values of 2, 0.9, and 2 mg/ml,
      respectively. Beer congener (0.05-2 mg/ml) induced the contraction of
      longitudinal muscle from guinea pig ileum in a dose-dependent manner. This effect
      was not affected by either tetrodotoxin (10(-6)M) or ketanserin (10(-7)-10(-5)M),
      an antagonist for the 5-HT2 receptor. On the other hand, 4-DAMP (10(-8)-10(-5)M),
      an antagonist for the muscarinic M3 receptor, inhibited the contraction of the
      longitudinal muscle induced by beer congener (2 mg/ml) dose dependently.
      CONCLUSIONS: Beer congener stimulates gastrointestinal motility via the
      muscarinic M3 receptor.

PMID- 12045477
TI  - Hepatocyte growth factor, epidermal growth factor, and placenta growth factor
      concentrations in peripheral blood of pregnant women with alcohol abuse.
AB  - BACKGROUND: Alcohol abuse during pregnancy compromises fetal development not only
      directly but also by abnormal placental function. Therefore, hepatocyte growth
      factor (HGF), epidermal growth factor (EGF), and placenta growth factor (PlGF),
      expressed in the placenta, may play a role in alcohol-induced placental
      dysfunction. METHODS: Peripheral venous blood samples were collected from 40
      pregnant alcohol-abusing women and 42 abstinent pregnant women from gestational
      weeks 4 to 41. Plasma HGF and serum PlGF were assessed by enzyme-linked
      immunosorbent assays and serum EGF by an immunofluorometric assay. RESULTS:
      Plasma HGF concentrations were similar in alcohol-abusing and abstinent mothers,
      although in the latter women these concentrations increased with advancing
      pregnancy. Serum EGF concentrations were consistently higher in alcohol-abusing
      than in abstinent mothers. In the latter, these concentrations decreased with
      advancing pregnancy. Serum PlGF concentrations increased with advancing pregnancy
      in both groups and were higher in alcohol-abusing mothers during the second and
      third trimesters but not during the first. CONCLUSIONS: Alcohol abuse during
      pregnancy is associated with changes in maternal circulating EGF and PlGF but not
      HGF concentrations. The observed changes may be caused by alcohol per se or may
      be secondary to possible alcohol-induced changes in placental physiology.

PMID- 12045478
TI  - Effect of ethanol self-administration on mu- and delta-opioid receptor-mediated G
      protein activity.
AB  - BACKGROUND: This study examined the effects of ethanol self-administration on mu-
      and delta-opioid receptor-mediated G-protein activity in specific brain regions
      of male Long Evans rats. METHODS: Rats were trained to self-administer ethanol by
      using a home-cage modification of the sucrose substitution paradigm. After 30 to
      40 days of sucrose or sucrose/15% ethanol self-administration (20 min sessions,
      Monday-Friday), rats were killed for autoradiographic assays. Coronal sections of
      brains from sucrose and ethanol self-administering rats were collected and
      processed for basal and mu- and delta-stimulated [35S]guanosine-5'-O-(gamma-thio)
      triphosphate (GTPgammaS) binding. Sections were exposed to film and then analyzed
      by using computer-assisted densitometry to determine levels of basal and agonist
      stimulated [35S]GTPgammaS binding. RESULTS: Mu-opioid-stimulated [35S]GTPgammaS
      binding was decreased in the prefrontal cortex of brains from ethanol compared
      with sucrose self-administering rats. Mu-opioid-stimulated [35S]GTPgammaS binding
      was unchanged in the cingulate cortex, caudate-putamen, nucleus accumbens,
      amygdala, hypothalamus, thalamus, and locus ceruleus of ethanol compared with
      sucrose self-administering rats. Basal and delta-opioid-stimulated [35S]GTPgammaS
      binding did not differ between the two groups in the prefrontal cortex or any
      other region analyzed. CONCLUSIONS: These data demonstrate decreased mu-opioid
      mediated G-protein activity in the prefrontal cortex of ethanol self
      administering rats and suggest an interaction between ethanol and mu-opioid
      receptors in this region.

PMID- 12045479
TI  - Sex differences in ethanol-induced hypnosis and hypothermia in young Long-Evans
      rats.
AB  - INTRODUCTION: Females experience greater liver damage, have reduced brain size,
      and have greater memory deficits than do males with a similar history of
      alcoholism. Females have higher peak alcohol levels and faster elimination rates
      than males. Our goal was to study sex differences in the response of young
      ethanol-naive outbred Long-Evans rats to acute ethanol exposure so that we may
      better understand why females are more sensitive to alcohol toxicity than males.
      METHODS: Females aged 49 days and males aged 43 days, weighing 153.6 and 177.5 g,
      respectively, were tested for their initial response to ethanol. Fasted (12 hr)
      females (in diestrous) and males were given an intraperitoneal injection of 3.0
      g/kg of ethanol (v/v in 0.9% sterile saline). Body temperature, loss of the
      righting reflex (LORR), return of the righting reflex, and tail blood alcohol
      concentration (BAC) were monitored. RESULTS: LORR occurred at the same time in
      females and males. The return of the righting reflex occurred later in males than
      in females. BACs were the same in the males and females except at LORR, when BAC
      was lower in the males. Acute ethanol tolerance developed in more males than
      females. Females demonstrated a slower recovery from peak ethanol-induced
      hypothermia than males. The proportions of lean body mass, ethanol elimination,
      and ethanol metabolism were similar in the females and males. CONCLUSIONS:
      Ethanol-naive young male and female Long-Evans rats demonstrated sex differences
      in their initial responses to ethanol. Males were more sensitive than females to
      the hypnotic effect of ethanol, whereas females were more sensitive than males to
      ethanol-induced hypothermia. In addition, more males than females developed acute
      ethanol tolerance. Investigating the mechanisms underlying these differences may
      help us to understand why females experience more of the adverse effects of
      alcohol consumption than males.

PMID- 12045480
TI  - Speed and efficiency but not accuracy or timing deficits of limb movements in
      alcoholic men and women.
AB  - BACKGROUND: Lesions of the cerebellum, a concomitant of alcoholism, can disrupt
      quality and regularity of movement. Whether evidence for such dysfunction lingers
      in patients with uncomplicated alcoholism, which is known to affect cerebellar
      structural integrity, is controversial. METHODS: We used quantitative measures to
      examine component processes of five classes of movement associated with regional
      cerebellar function: limb ataxia (alternated finger tapping and variants of the
      finger-to-nose and heel-to-shin tests), paced tapping, eye-hand coordinated
      tracing, timed response reflecting preparation and execution time, and postural
      stability. The subjects examined were 39 abstinent alcoholics (13 men and 26
      women) and 21 age-matched controls (9 men and 12 women). For limb ataxia, the
      dependent measures were the trajectory deviation from the subject's own average
      movement path and the speed of travel from beginning points to endpoints.
      RESULTS: Repeated-measures analysis of variance comparing movement speed of
      finger to nose and heel to shin yielded significant interactions in all
      conditions (p < 0.007); this indicated that the alcoholics were relatively slower
      in the upper- than lower-limb tasks. Movements by the alcoholic men were
      significantly slower but less deviant from an ideal trajectory in all upper-limb
      conditions than those of the control men (p < 0.002). Although measures of lower
      limb movement trajectory did not distinguish the groups, tests of ataxia of
      stance and gait did. The groups did not differ, however, on tests of timed
      tapping or sinusoid tracing. CONCLUSIONS: Alcohol-related postural instability in
      abstinent alcoholics is functional evidence supporting the postulated damage to
      the anterior superior vermis. Altered speed or accuracy trade-offs, with
      alcoholics moving slower to attain equivalent or even smaller trajectory
      deviations, are symptomatic of cerebellar hemisphere dysfunction that is
      characterized by deliberation of otherwise automatic movements.

PMID- 12045481
TI  - The corticotropin-releasing factor/urocortin system and alcohol.
AB  - This article represents the proceedings of a symposium at the RSA meeting in
      Montreal, Canada. The organizer was Andrey E. Ryabinin, and the chair was George
      F. Koob. The presentations were (1) Introduction, by Stephen C. Heinrichs; (2)
      Role of CRF and its receptors in the hypothalamic-pituitary-adrenal response to
      alcohol, by Soon Lee and Catherine Rivier; (3) A role for CRF in the allostasis
      of alcohol dependence, by George F. Koob and Amanda J. Roberts; (4) CRF and
      alcohol: Lessons from knockouts, microinjections, and microdialysis, by M. Foster
      Olive, Kristin K. Mehmert, R. Camarini, Joseph A. Kim, Heather N. Koenig,
      Michelle A. Nannini, and Clyde W. Hodge; and (5) Selective sensitivity of
      urocortin-containing neurons to alcohol self-administration, by Andrey E.
      Ryabinin and Ryan K. Bachtell.

PMID- 12045483
TI  - Pathogenesis of alcoholic liver disease--recent advances.
AB  - The article summarizes the proceedings of a symposium on recent advances in
      research on the pathogenesis of alcoholic liver disease at the 2001 RSA meeting
      in Montreal, Canada. The chairs were Amin A. Nanji and Samuel W. French. The
      presentations were (1) Role of inflammatory mediators in alcoholic liver injury
      by Amin A. Nanji, (2) Role of endotoxin, lipopolysaccharide binding protein, CD14
      and Toll receptors in alcoholic liver injury by Grace Su, (3) Fatty acid ethyl
      esters: toxicity, metabolism and markers of ethanol intake by Michael Laposata,
      and (4) Cyclic changes in gene expression when rats are fed alcohol at a constant
      rate by Samuel W. French.

PMID- 12045482
TI  - College binge drinking: what is it? Who does it?
AB  - This article presents research included in the symposium at the 2001 Research
      Society on Alcoholism meeting in Montreal, Canada. James Lange was the organizer
      and provided the introduction of this article. Gayle Boyd was the chairperson,
      and Mary Larimer was the discussant. The presentations were (1) Defining binge
      drinking quantities through resulting BACs, by James E. Lange and Robert B. Voas;
      (2) Environmental predictors of heavy episodic drinking events, by John D. Clapp;
      (3) Parents' continuing role in college binge drinking, by Rob Turrisi, Racheal
      Taki, and James Jaccard; and (4) Motivations of binge drinkers, by Mark B.
      Johnson, Robert B. Voas, and James E. Lange. The summary and discussion were
      provided by Mary Larimer.

PMID- 12045484
TI  - Expectancy and risk for alcoholism: the unfortunate exploitation of a fundamental
      characteristic of neurobehavioral adaptation.
AB  - Psychological investigations of alcohol expectancies over the last 20 years,
      using primarily verbal techniques, have strongly supported expectancies as an
      important mediator of biological and environmental antecedent variables that
      influence risk for alcohol use and abuse. At the same time, rapid developments in
      neuroscience, cognitive science, affective science, computer science, and
      genetics proved to be compatible with the concept of expectancy and, in some
      cases, used this concept directly. By using four principles that bear on the
      integration of knowledge in the biological and behavioral sciences-consilience,
      conservation, contingency, and emergence-these developments are merged into an
      integrated explanation of alcoholism and other addictions. In this framework,
      expectancy is seen as a functional approach to adaptation and survival that has
      been manifested in multiple biological systems with different structures and
      processes. Understood in this context, addiction is not a unique behavioral
      problem or special pathology distinct from the neurobehavioral substrate that
      governs all behavior, but is rather a natural (albeit unfortunate) consequence of
      these same processes. The ultimate intent is to weave a working heuristic that
      ties together findings from molecular and molar levels of inquiry and thereby
      might help direct future research. Such integration is critical in the
      multifaceted study of addictions.

PMID- 12045485
TI  - Neurologic and psychiatric complications of antiretroviral agents.

PMID- 12045486
TI  - B cell activation in peripheral blood and lymph nodes during HIV infection.
AB  - BACKGROUND: The spontaneous in-vitro antibody synthesis observed in unstimulated
      lymphocyte cultures from HIV-infected patients closely reflects the in-vivo
      activation of the B cell compartment; however, the mechanisms underlying this
      phenomenon are far from clear. METHODS: We compared the ability of peripheral
      blood mononuclear cells (PBMC) and lymph-node cells (LNC) from 10 HIV-infected
      patients to produce in vitro HIV-specific and total Ig spontaneously, and we
      correlated these parameters with tumour necrosis factor alpha (TNF-alpha)
      expression by CD4 T cells, viral dissemination in the organism, and the extent of
      HIV spread into lymph-node germinal centres, measured by in-situ hybridization
      (ISH). RESULTS: In-vitro spontaneous synthesis of both HIV-specific and total
      antibody was significantly higher in PBMC than in LNC; the two variables showed a
      good correlation in LNC, but not in PBMC. In both compartments, no correlation
      was found between B cell activation and the percentage of CD4 T cells expressing
      TNF-alpha, which was increased compared with seronegative donors. Furthermore, no
      correlation was found between in-vitro spontaneous antibody synthesis and the
      number of T cells containing proviral HIV in PBMC and LNC, or the plasma levels
      of HIV RNA. On the contrary, a good correlation was found between HIV-specific B
      cell activation and the extent of viral spread into lymph-node germinal centres,
      evaluated by ISH. CONCLUSION: These data suggest that the adhesion of HIV virions
      to the follicular dendritic cell network in lymph-node germinal centres may
      primarily contribute to sustaining the steady B cell activation observed in HIV
      infected patients.

PMID- 12045487
TI  - Genotypic and phenotypic analyses of HIV-1 in antiretroviral-experienced patients
      treated with tenofovir DF.
AB  - OBJECTIVE: To evaluate the virologic responses and mutational profiles in
      antiretroviral-experienced patients adding tenofovir DF once-daily to their
      existing regimens. DESIGN: Resistance analyses were performed for patients in a
      phase II placebo-controlled clinical trial of tenofovir DF. METHODS: HIV-1
      reverse transcriptase and protease genes from plasma samples were analyzed
      genotypically and phenotypically at baseline, week 24, and week 48. RESULTS: Of
      184 patients, 173 (94%) had baseline HIV-1 expressing one or more nucleoside
      reverse transcriptase inhibitor-associated resistance mutation. Protease
      inhibitor and non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance
      mutations were observed in 57% and 32% of patients, respectively. Compared to
      placebo, significant reductions in HIV-1 RNA were observed for tenofovir DF
      treated patients who had thymidine analog- (TAM), lamivudine- (M184V), NNRTI- or
      protease inhibitor-associated mutations. Patients with phenotypic susceptibility
      to tenofovir within 4-fold of wild-type responded durably to tenofovir DF 300 mg
      therapy with a decline in plasma HIV-1 RNA of > or = 0.5 log10 copies/ml; few
      patients had a more than 4-fold reduced susceptibility to tenofovir at baseline.
      Four patients (2%) developed the K65R mutation (selected by tenofovir in vitro)
      and showed 3- to 4-fold reductions in tenofovir susceptibility but no evidence of
      rebound viremia. Thirty-four percent of patients developed additional TAMs,
      coincident with concurrent zidovudine or stavudine therapy, but also showed
      durable HIV-1 reductions. There was no evidence of novel resistance to tenofovir.
      CONCLUSIONS: Adding tenofovir DF 300 mg to an existing regimen in patients with
      ongoing viral replication and a wide range of genotypic resistance patterns
      resulted in significant and durable HIV-1 RNA reductions. In addition, there was
      a low incidence of genotypic or phenotypic resistance to tenofovir DF arising
      during 48 weeks of therapy.

PMID- 12045488
TI  - Adherence of different Candida dubliniensis isolates in the presence of
      fluconazole.
AB  - BACKGROUND: The recently described yeast species Candida dubliniensis is closely
      related to C. albicans and has been recovered predominantly from the oral
      cavities of HIV-infected individuals and AIDS patients who are often receiving
      fluconazole as prophylactic or therapeutic treatment for oropharyngeal
      candidiasis. Like C. albicans, C. dubliniensis secretes aspartic proteinases
      which in C. albicans have been shown to be involved in adherence. OBJECTIVE: To
      explain the increasing prevalence of C. dubliniensis in AIDS patients and to
      investigate the virulence factors of this yeast. METHODS: An in vitro assay was
      developed to compare the adherence to epithelial cells of C. dubliniensis from
      HIV-patients with that of C. albicans. RESULTS: All C. albicans isolates adhered
      better than the 22 C. dubliniensis isolates. In the presence of fluconazole, the
      C. dubliniensis isolates tested showed increased adherence as compared with
      controls without fluconazole. In contrast, all C. albicans isolates decreased in
      adherence to epithelial cells in the presence of fluconazole independently of
      their in vitro susceptibility to this drug. Proteinase antigens are present on
      the surface of C. dubliniensis cells adherent to epithelial target cells. In the
      presence of fluconazole this proteinase antigen was more strongly expressed.
      CONCLUSION: Increased adherence of C. dubliniensis strains in the presence of
      fluconazole could explain its high recovery rate from HIV-positive patients in
      recent years. The induction of proteinase secretion in the presence of
      fluconazole found for most of the C. dubliniensis isolates could be one of the
      factors involved in adherence.

PMID- 12045489
TI  - Segregation of R5 and X4 HIV-1 variants to memory T cell subsets differentially
      expressing CD62L in ex vivo infected human lymphoid tissue.
AB  - OBJECTIVE: The mechanisms of HIV-triggered immunodeficiency were examined by
      determining the segregation of R5 and X4 HIV-1 variants into memory T cell
      subsets expressing differentially a homing receptor, CD62L-selectin, in human
      lymphoid tissue. METHODS: Subpopulations of CD3 and intracellular p24 gag
      positive cells in human lymphoid tissue infected ex vivo with X4 HIV-1 variant
      NL4-3 and R5 HIV-1 variant AD8 were analysed for expression of the T cell memory
      markers CD45RO and CD45RA, the T cell homing receptor for lymphoid tissue CD62L,
      and the HIV-1 coreceptors CCR5 and CXCR4. RESULTS: Memory CD4 T cells were the
      predominant targets for productive infection of lymphoid tissue ex vivo with both
      R5 and X4 HIV-1. R5 HIV-1 predominantly infected CD62L-negative memory T cells,
      which selectively express CCR5. In contrast, X4 HIV-1 variants predominantly
      infected CD62L+ memory T cells, although CXCR4 coreceptor was equally expressed
      by memory T cells of both CD62L-positive and CD62L-negative subsets. A high
      proportion of X4 HIV-1, but not of R5 HIV-1, productively infected T cells,
      displayed a CD45RA+CD45RO+ phenotype. CONCLUSION: The selective expression of the
      CCR5 coreceptor by CD62L-negative terminally differentiated memory T cells
      correlates with the preferential productive infection of these cells with the R5
      HIV-1 variant. The predominance of X4 HIV-1 variants in less-differentiated
      memory T cells may be related to their recent activation state, as suggested by
      the coexpression of both CD45RA and CD45RO molecules on their surface.
      Differential homing of CD62L-positive and CD62L-negative cells suggests different
      routes of dissemination of X4 and R5 viruses.

PMID- 12045490
TI  - Normalization of natural killer cell function and phenotype with effective anti
      HIV therapy and the role of IL-10.
AB  - OBJECTIVES: Natural killer (NK) cell function is likely to be important in
      controlling HIV infection and opportunistic pathogens. We therefore evaluated NK
      function and phenotype over the course of antiretroviral therapy (ART) and
      examined the potential mechanisms of altered NK activity in HIV infection.
      METHODS: We measured NK cell percentage, NK cytolytic activity (both by flow
      cytometry) and plasma IL-10 concentrations (by enzyme-linked immunosorbent assay)
      in 10 HIV-seropositive patients before and over one year of effective ART. To
      examine potential mechanisms of altered NK activity, we measured NK receptor
      expression in ART treated and untreated HIV-positive individuals by flow
      cytometry. As IL-10 enhances NK activity, we studied the effect of IL-10 on NK
      receptor expression and activity in peripheral blood mononuclear cells (PBMC)
      from HIV-seronegative individuals. RESULTS: NK cytolytic activity was elevated in
      HIV infection and decreased with ART to levels observed in HIV-negative
      individuals. A greater proportion of NK cells from untreated HIV-positive
      individuals expressed the NK receptors CD158a and CD161 than either HIV-negative
      volunteers or effectively treated HIV-positive patients. NK cells from PBMC
      incubated with IL-10 demonstrated increases in CD158a, CD161 and CD94 expression
      and increases in cytolytic activity. The treatment-associated decrease in NK
      activity paralleled a decrease in IL-10 production. CONCLUSION: The observation
      that IL-10 alters NK receptor expression similar to that observed in HIV
      infection, and the fact that NK receptor expression and activity normalize in
      parallel with ART-induced reduction of circulating IL-10 levels supports a role
      for IL-10 in NK cell activity and HIV immunopathogenesis.

PMID- 12045492
TI  - Reduced intravertebral bone marrow fat in HIV-infected men.
AB  - OBJECTIVE: To measure intravertebral bone marrow fat in HIV-infected men. DESIGN:
      A cross-sectional study of HIV-positive men, subcategorized by lipodystrophy and
      antiretroviral status, and healthy age- and body mass index (BMI)-matched HIV
      negative controls. SETTING: A tertiary care academic medical institution.
      PATIENTS: Fifteen HIV-infected men and nine age- and BMI-matched healthy control
      subjects were recruited for bone density, intravertebral bone marrow fat, and
      body composition measurements. METHODS: Magnetic resonance spectroscopy was used
      to measure intravertebral marrow fat. Quantitative computed tomography was used
      to quantify visceral and subcutaneous fat. Dual energy X-ray absorptiometry was
      used to determine lumbar spine bone density. Statistical comparisons were
      performed according to HIV, lipodystrophy, and protease inhibitor (PI) exposure
      status. RESULTS: Intravertebral marrow fat was reduced in HIV-infected men (N =
      15) compared with healthy HIV-negative controls (N = 9) (28.5 +/- 8.0 versus 37.3
      +/- 12.5%, P = 0.04). Intravertebral bone marrow fat was most severely reduced in
      HIV-infected men with lipodystrophy compared with healthy HIV-negative controls
      (25.6 +/- 8.8% versus 37.3 +/- 12.5%, P = 0.04). Furthermore, nelfinavir (P =
      0.02) was associated with decreased intravertebral marrow fat and indinavir (P <
      0.05) was associated with increased intravertebral marrow fat in HIV-infected
      subjects. CONCLUSION: We demonstrated reduced intravertebral marrow fat in HIV
      infected men using magnetic resonance spectroscopy. Notably, reduced marrow fat
      occurred in the setting of reduced bone density and may be affected by specific
      PI and lipodystrophy status. Further studies are necessary to determine the
      relationship between marrow fat and osteopenia and the effect of antiretroviral
      therapy on marrow fat in this population.

PMID- 12045491
TI  - Tenofovir DF in antiretroviral-experienced patients: results from a 48-week,
      randomized, double-blind study.
AB  - OBJECTIVE: To evaluate the safety and efficacy of once daily doses of tenofovir
      DF (TDF) administered in combination with other antiretroviral therapy (ART) in
      treatment-experienced HIV-1-infected patients with incomplete virological
      suppression. DESIGN: One-hundred and eighty-nine subjects with plasma HIV-1 RNA
      levels between 400 and 100,000 copies/ml and stable ART (> or = 8 weeks) were
      randomized (2 : 2 : 2 : 1 ratio) to add TDF 75 mg, 150 mg, or 300 mg or placebo
      to existing ART in a double-blinded manner. After 24 weeks, patients initially
      randomized to placebo received blinded TDF 300 mg. METHODS: Efficacy was analyzed
      by the mean changes HIV-1 RNA levels (log10 copies/ml plasma; DAVG(xx)) from week
      0 to weeks 4, 24, and 48. Safety was analyzed by incidence of grade 3 or 4
      clinical and laboratory adverse events. RESULTS: At baseline, patients had mean
      4.6 years prior ART use with 94% having HIV-1 with nucleoside-associated
      resistance mutations. There were statistically significant decreases in DAVG(4)
      and DAVG(24) for all doses of TDF compared with placebo, with the greatest effect
      seen with TDF 300 mg (DAVG(4), -0.62, P < 0.001; DAVG(24), -0.58; P < 0.001;
      DAVG(48), -0.62). The incidence of adverse events was similar among the TDF
      groups and placebo through week 24. Throughout the 48-week study, no significant
      changes in renal function were observed. CONCLUSIONS: In treatment-experienced
      patients with baseline nucleoside resistance mutations, TDF provided dose
      related, durable reductions in HIV-1 RNA. Through 24 weeks, the safety profile of
      TDF was similar to that of placebo.

PMID- 12045494
TI  - HIV prevalence and risk behaviour in young drug users in Amsterdam.
AB  - OBJECTIVES: To assess the HIV prevalence and risk behaviour among regular young
      drug users (YDU) in Amsterdam. DESIGN: Subjects were 282 YDU (using heroin,
      cocaine, methadone and/or amphetamines at least 3 days/week) aged 30 years or
      less who participated in a cross-sectional survey in Amsterdam in 1998.
      Participants were recruited both directly (41%) through healthcare institutions,
      and indirectly (59%) by referrals from YDU already enrolled. A comparison sample
      of YDU from the Amsterdam Cohort Study recruited between 1985 and 1989 was used
      to describe trends in HIV prevalence and risk behaviour. RESULTS: Mean age was 25
      years, 22% were women, 39% had at least once injected drugs, and 22% currently
      injected in 1998. Cocaine was more often used regularly (70%) than heroin (42%).
      Of the 282 YDU, 21 (7.4%) were infected with HIV. Among those who had injected
      drugs, HIV prevalence was 16.2%. Among those who had never injected, the
      prevalence of HIV infection was 1.8%. A history of injecting declined from 83% in
      1985-1989 to 56% in 1998. Compared with 1985-1989, the lack of a recent steady
      partner appeared to be an important risk factor for a positive HIV status among
      injectors in 1998, whereas borrowing of used needles/syringes was no longer a
      risk factor. CONCLUSION: The use of cocaine among YDU is very popular in
      Amsterdam. A strong decrease in injecting behaviour has taken place, but among
      those who inject, risk behaviour is still considerable, and HIV infection is
      still widespread. Preventative activities should be expanded, specifically among
      YDU.

PMID- 12045493
TI  - HIV, syphilis and heterosexual bridging among Peruvian men who have sex with men.
AB  - OBJECTIVES: To determine prevalence of and risk factors associated with HIV and
      syphilis seropositivity and estimate incidence of HIV infection among Peruvian
      men who have sex with men (MSM) and characterize behaviors of men who report sex
      with both men and women ('bridgers'). DESIGN: Cross-sectional study of MSM in
      Lima, Peru. METHODS: Four-hundred and fifty-one MSM (of whom 442 responded to the
      question regarding sexual orientation) recruited through street outreach. Each
      was interviewed and underwent serologic testing for syphilis and HIV, including
      the less sensitive enzyme immunoassay test to estimate HIV incidence. RESULTS:
      Overall, HIV and syphilis prevalence were 18.5% and 16.0%, respectively, with
      highest prevalence among cross-dressers (33.3% and 51.1%, respectively). The
      estimated overall HIV seroincidence was 11.2% per year (95% confidence interval,
      4.8-23.6). Overall, 47.1% of men reported ever having sex with a woman: 78.6% of
      men self-identifying as heterosexuals, 85.1% of bisexuals, 35.5% of homosexuals,
      and 12.5% of cross-dressers. Of these, 26.5% were 'bridgers', of whom 55%
      reported two or more female partners during the last year. 'Bridgers' were less
      likely to have always used condoms during the past year for vaginal sex (17%)
      than for insertive anal sex with men (25.5%). CONCLUSIONS: Among MSM in Peru, HIV
      and syphilis prevalence and HIV incidence were high, especially among cross
      dressers. The high prevalence of bisexuality and low rates of consistent condom
      use, especially with female sexual partners indicates potential HIV transmission
      into the heterosexual population.

PMID- 12045495
TI  - Complete mapping of a novel HLA A*6801-restricted HIV-1 Tat epitope directly with
      a rapid modified enzyme-linked immunospot assay.
AB  - We identified a novel HLA A*6801-restricted HIV-1 Tat-derived cytotoxic T
      lymphocyte (CTL) epitope using an adapted enzyme-linked immunospot assay that
      allows the rapid ex vivo identification of CTL epitopes together with their
      associated HLA Class I restriction elements. The optimal 11 amino acid residue
      Tat epitope efficiently stabilized the refolding of monomeric peptide-HLA A6801
      complexes in vitro and fluorochrome-labelled, tetrameric peptide-HLA A6801
      complexes stained CD8 T cells specific for this epitope directly ex vivo.

PMID- 12045496
TI  - Discordant responses during antiretroviral therapy: role of immune activation and
      T cell redistribution rather than true CD4 T cell loss.
AB  - We studied T cell dynamics in four patients who initially responded well to
      highly active antiretroviral therapy (HAART) but subsequently experienced
      virological failure. Maintenance of peripheral blood CD4T cell counts was
      associated with low levels of immune activation. Low reactivity to rebounding
      virus may preserve normal T lymphocyte distribution over blood and tissues and be
      associated with stable peripheral blood T cell numbers in virological failures to
      HAART.

PMID- 12045497
TI  - Decreased recovery of replication-competent HIV-1 from peripheral blood
      mononuclear cell-derived monocyte/macrophages of HIV-positive patients after 3
      years on highly active antiretroviral therapy.
AB  - We studied the release of p24 antigen from peripheral blood mononuclear cell
      derived monocyte/macrophages obtained from 13 HIV-positive patients receiving
      highly active antiretroviral therapy (HAART). Although HIV-infected
      monocyte/macrophages were detected in 80% of patients after 36 months of
      continuous treatment, additional exposure to HAART reduced the chance of
      detecting HIV-releasing monocyte/macrophages. Therefore, after more than 3 years
      of HAART, recently infected monocytes may play a less important role as a source
      of emerging HIV-1 upon HAART interruption.

PMID- 12045498
TI  - Severe and Norwegian scabies are strongly associated with retroviral (HIV-1/HTLV
      1) infection in Bahia, Brazil.
AB  - Severe scabies has been associated with HTLV infection. To evaluate the impact of
      HTLV-I/HIV-1 co-infection on the clinical presentation of scabies, we reviewed 91
      cases of scabies in Bahia, Brazil, during a 3 year period. Infections by HIV-1
      (50%), HTLV-I (32%), and both (20%) were highly prevalent. Crusted or severe
      scabies were strongly associated with HTLV-I and, to a lesser degree, with HIV-1
      infection. Co-infected patients had a higher risk of death (P = 0.01). Severe
      forms of scabies were highly predictive of double retroviral infection.

PMID- 12045499
TI  - Association between sexual disturbances and sexual hormones with specific
      antiretroviral drugs.
AB  - Sexual disturbances have been related to protease inhibitor therapy, but the
      effect of specific protease or non-nucleoside reverse transcriptase inhibitors is
      largely unknown. We analysed the rate of sexual dysfunction and the sexual
      hormonal profile in patients undergoing antiretroviral therapy. All
      antiretroviral drugs were associated with different degrees of sexual
      dysfunction; the highest rates with indinavir and the lowest with nevirapine.
      Although these drugs were associated with increases in testosterone and 17 beta
      oestradiol, sexual disturbances were not related to alterations in the sexual
      hormonal pattern.

PMID- 12045500
TI  - Evaluating the risk of HIV transmission through unprotected orogenital sex.
AB  - We analysed a cohort of heterosexual HIV- serodiscordant couples with the aim of
      evaluating the risk of transmission ascribed to unprotected orogenital
      intercourse. A total of 135 seronegative individuals (110 women and 25 men),
      whose only risk exposure to HIV was unprotected orogenital sex with their
      infected partner, registered 210 person-years of follow-up. After an estimated
      total of over 19,000 unprotected orogenital exposures with the infected partner
      not a single HIV seroconversion occurred.

PMID- 12045501
TI  - Safety of abacavir therapy after temporary interruptions in patients without
      hypersensitivity reactions to the drug.

PMID- 12045502
TI  - HIV-1 dynamics in haemodialysis patients.

PMID- 12045504
TI  - Lymphoma developing shortly after the onset of highly active antiretroviral
      therapy in HIV-infected patients.

PMID- 12045503
TI  - Resolution of multidrug-refractory oesophageal candidiasis in an AIDS patient
      after treatment with caspofungin.

PMID- 12045505
TI  - Galactorrhoea and hyperprolactinemia associated with HIV postexposure
      chemoprophylaxis.

PMID- 12045506
TI  - Adhesive capsulitis of the shoulder in an HIV patient treated with nelfinavir.

PMID- 12045507
TI  - Improved methods and assumptions for estimation of the HIV/AIDS epidemic and its
      impact: Recommendations of the UNAIDS Reference Group on Estimates, Modelling and
      Projections.
AB  - UNAIDS and WHO produce biannual country-specific estimates of HIV/AIDS and its
      impact. These estimates are based on methods and assumptions that reflect the
      best understanding of HIV epidemiology and demography at the time. Where
      significant advances are made in epidemiological and demographic research, the
      methods and assumptions must evolve to match these advances. UNAIDS established
      an Epidemiology Reference Group in 1999 to advise them and other organisations on
      HIV epidemiology and methods for making estimates and projections of HIV/AIDS.
      During the meeting of the reference group in 2001, four priority areas were
      identified where methods and assumptions should be reviewed and perhaps modified:
      a) models of the HIV epidemic, b) survival of adults with HIV-1 in low and middle
      income countries, c) survival of children with HIV-1 in low and middle income
      countries, and d) methods to estimate numbers of AIDS orphans. Research and
      literature reviews were carried out by Reference Group members and invited
      specialists, prior to meetings held during 2001-2. Recommendations reflecting the
      consensus of the meeting participants on the four priority areas were determined
      at each meeting. These recommendations were followed in UNAIDS and WHO
      development of country-specific estimates of HIV/AIDS and its impact for end of
      2001.

PMID- 12045508
TI  - Chronic low back pain and fusion: a comparison of three surgical techniques: a
      prospective multicenter randomized study from the Swedish lumbar spine study
      group.
AB  - STUDY DESIGN: A multicenter randomized study with a 2-year follow-up period and
      an independent observer was conducted. OBJECTIVE: To compare three commonly used
      surgical techniques to achieve lumbar fusion primarily in terms of their ability
      to reduce pain and decrease disability in patients with severe chronic low back
      pain. SUMMARY OF BACKGROUND DATA: Lumbar fusion can be used to reduce pain and
      decrease disability in patients with chronic low back pain, and different
      surgical techniques are available. The reported results after fusion surgery vary
      considerably, but most studies are retrospective and/or performed on
      heterogeneous patient groups. Spine surgeons commonly use the techniques
      presented in this report. However, in the absence of randomized trials it is
      difficult to know whether any one of them is better than the others for these
      patients. METHODS: From 1992 through 1998, 294 patients referred to 19 spinal
      centers were blindly randomized into four treatment groups: three surgical groups
      (n = 222) and one nonsurgical group (n = 72). The sociodemographic and clinical
      characteristics did not differ among the groups. Eligibility included patients 25
      to 65 years of age with therapy-resistant chronic low back pain that had
      persisted for at least 2 years and radiologic evidence of disc degeneration
      (spondylosis) at L4-L5, L5-S1, or both. Only patients randomized to one of three
      surgical groups were analyzed in the current study: Group 1 (posterolateral
      fusion; n = 73), Group 2 (posterolateral fusion combined with variable screw
      placement, an internal fixation device; n = 74), and Group 3 (posterolateral
      fusion combined with variable screw placement and interbody fusion; n = 75). The
      "circumferential fusion" in Group 3 was performed either as an anterior lumbar
      interbody fusion (n = 56) or as a biomechanically similar posterior lumbar
      interbody fusion (n = 19). The groups were composed of 51%, 58%, and 40% men
      respectively, and the respective mean ages were 44, 43, and 42 years. The
      patients had experienced low back pain for at least 2 years (mean, approximately
      8 years). They had been on sick leave for approximately 3 years. Pain was
      measured by a visual analog scale, and disability was assessed by the Oswestry
      Low Back Pain Questionnaire, the Million Visual Analogue Score, and the General
      Function Score. Depressive symptoms were measured by the Zung Depression Scale.
      The global overall rating of the result was assessed by the patient and an
      independent observer after 2 years. Hospitalization data including operation
      time, blood loss, blood transfusion, and days of hospitalization in connection
      with surgery were reported, along with complications and the fusion rate. Records
      from the Swedish Social Insurance Board providing information on sick leave and
      economic compensation for Swedish residents were used to evaluate the patients'
      work status. RESULTS: An independent observer examined 201 (91%) of 222 patients
      after 2 years, after 18 "group changers" and 3 dropouts had been excluded from
      the analyses. All surgical techniques were found to reduce pain and decrease
      disability substantially, but no significant differences were found among the
      groups. In all three groups, the patients rated the overall outcome similarly, as
      did the independent observer. The more demanding techniques in Groups 2 and 3
      consumed significantly more resources in terms of operation time, blood
      transfusions, and days in hospital after surgery. The early complication rate was
      6% in Group 1, 16% in Group 2, and 31% in Group 3. The fusion rate, as evaluated
      by plain radiograph, was 72% in Group 1, 87% in Group 2, and 91% in Group 3.
      CONCLUSIONS: All the fusion techniques used in the study could reduce pain and
      improve function in this selected group of patients with severe chronic low back
      pain. There was no obvious disadvantage in using the least demanding surgical
      technique of posterolateral fusion without internal fixation.

PMID- 12045509
TI  - Effectiveness of four conservative treatments for subacute low back pain: a
      randomized clinical trial.
AB  - STUDY DESIGN: A randomized, assessor-blinded clinical trial was conducted.
      OBJECTIVE: To investigate the relative effectiveness of three manual treatments
      and back school for patients with subacute low back pain. SUMMARY OF BACKGROUND
      DATA: Literature comparing the relative effectiveness of specific therapies for
      low back pain is limited. METHODS: Among the 5925 inquiries, 206 patients met the
      specific admission criteria, and 200 patients randomly received one of four
      treatments for 3 weeks: back school, joint manipulation, myofascial therapy, and
      combined joint manipulation and myofascial therapy. These patients received
      assessments at baseline, after 3 weeks of therapy, and 6 months after the
      completion of therapy. The primary outcomes were evaluated using visual analog
      pain scales and Roland-Morris activity scales. RESULTS: All four groups showed
      significant improvement in pain and activity scores after 3 weeks of care, but
      did not show further significant improvement at the 6-month follow-up assessment.
      No statistically significant between-group differences were found either at the 3
      week or 6-month reassessments. CONCLUSIONS: For subacute low back pain, combined
      joint manipulation and myofascial therapy was as effective as joint manipulation
      or myofascial therapy alone. Additionally, back school was as effective as three
      manual treatments.

PMID- 12045510
TI  - Effectiveness and cost-effectiveness analysis of neuroreflexotherapy for subacute
      and chronic low back pain in routine general practice: a cluster randomized,
      controlled trial.
AB  - STUDY DESIGN: A cluster randomized, controlled trial was performed. OBJECTIVES:
      To assess the clinical effectiveness and cost-effectiveness of adding patients'
      referral to neuroreflexotherapy intervention to the usual management of subacute
      and chronic low back pain in routine general practice. SUMMARY OF BACKGROUND
      DATA: Neuroreflexotherapy consists of the temporary implantation of epidermal
      devices in trigger points in the back and referred tender points in the ear. The
      efficacy of this procedure for treating subacute and chronic low back pain has
      been demonstrated in previous randomized, double-blind, controlled clinical
      trials. METHODS: Twenty-one primary care physicians working in seven primary care
      centers of the Spanish National Health Service in Palma de Mallorca, Spain, were
      randomly assigned to the intervention group (n = 11) or the control group (n =
      10). The physicians recruited patients who had low back pain that had lasted for
      14 or more days despite drug treatment and who did not meet criteria for surgery.
      The 45 patients recruited by physicians from the control group were treated
      according to the standard protocol, whereas the 59 patients recruited by
      physicians from the intervention group were, in addition, referred to
      neuroreflexotherapy intervention. The analysis of variables was performed taking
      into account that physicians, not patients, were randomly assigned. RESULTS:
      Patients underwent clinical evaluations at baseline and 15, 60, and 365 days
      later. At baseline, median intensity of pain was higher in patients undergoing
      neuroreflexotherapy than in control patients (visual analogue scale, 6.07; range,
      4.67-8.80 vs. 5.15, range 4.11-8.00) and median duration of pain was also higher
      (48.1, range 28.4-211.1 vs. 17.5, range 15.0-91.5 days). At the last follow-up
      visit, patients treated with neuroreflexotherapy showed greater improvement than
      did control patients in low back pain (visual analogue scale, 5.5; range, 3.7-8.8
      vs. 1.9; range, -1.2-3.0; P < 0.001); referred pain (visual analogue scale, 3.6;
      range, 2.7-7.3 vs. 0.6; range, -1.5-2.0; P = 0.001); and disability (Roland
      Morris scale, 8.7; range, 2.0-13.3 vs. 2.0; range, -1.5-6.7; P = 0.007).
      Moreover, neuroreflexotherapy intervention was associated with a significantly (P
      < 0.035) lower number of consultations to private or public specialists, fewer
      indications of radiographs by primary care physicians, lower cost of drug
      treatment, and less duration of sick leave throughout the follow-up period. There
      were also differences in favor of neuroreflexotherapy intervention in the cost
      effectiveness ratio for pain, disability, and quality of life that persisted in
      the most optimistic, the most conservative, and the average (break-even case)
      assumptions. CONCLUSIONS: Referral to neuroreflexotherapy intervention improves
      the effectiveness and cost-effectiveness of the management of nonspecific low
      back pain.

PMID- 12045511
TI  - Internal pressure measurements during burst fracture formation in human lumbar
      vertebrae.
AB  - STUDY DESIGN: In a laboratory study, 21 human lumbar spine segments were used to
      determine whether intraosseous pressure increases occur during axial-compressive
      loading conditions under two displacement rates. OBJECTIVE: To determine whether
      an intraosseous pressure rise is associated with burst fracture formation.
      SUMMARY OF BACKGROUND DATA: Burst fractures are high-speed injuries usually
      associated with neurologic deficit. An internal pressure rise has been implicated
      as a critical factor in burst fracture formation. The authors hypothesize that
      the internal pressure increases with increasing input velocity. METHODS: The
      internal pressure changes were measured in spine segments using two displacement
      rates: 10 mm/s (slow speed) and 2500 mm/s (high speed). Failure load and energy
      absorption were determined for both groups. The resultant fracture types were
      determined from postinjury radiographs. RESULTS: The initial peak internal
      pressure decreased from slow- to high-speed tests (P < 0.01). Overall peak
      pressure, failure load, and energy absorbed at failure were not significantly
      different. Slow-speed tests resulted in compression fractures, whereas high-speed
      tests resulted in burst and compression fractures. CONCLUSIONS: The current
      research did not support the current theory of burst fracture formation. There
      was a decrease in measured internal pressure from the slow- to high-speed groups,
      and burst fractures still were produced. The theory could be potentially modified
      to suggest that the nucleus entering the vertebral body acts as a wedge,
      splitting the vertebral body apart and enabling the bony fragments to be pushed
      into the canal space.

PMID- 12045512
TI  - Point of view.

PMID- 12045513
TI  - Corpectomy versus laminoplasty for multilevel cervical myelopathy: an independent
      matched-cohort analysis.
AB  - STUDY DESIGN: Matched patient cohorts using retrospective chart and radiographic
      review with independent clinical and radiographic follow-up were reviewed.
      OBJECTIVE: To compare the clinical and radiographic outcomes of multilevel
      corpectomy and laminoplasty using an independent matched-cohort analysis. SUMMARY
      OF BACKGROUND DATA: The treatment of choice for multilevel cervical myelopathy
      remains a matter of investigation. For the decompression of three or more motion
      segments, multilevel corpectomy and laminoplasty have proven effective while
      avoiding the pitfalls of laminectomy. Direct clinical comparisons of these two
      procedures are few in number and are limited by the heterogeneity in their
      patient groups. METHODS: Medical records of all patients treated for multilevel
      cervical myelopathy with either multilevel corpectomy or laminoplasty between
      1994 and 1999 at the Emory Spine Center were reviewed. From a pool of 38 patients
      meeting stringent inclusion and exclusion criteria, 13 patients who underwent
      multilevel corpectomy were blindly matched with 13 patients who underwent
      laminoplasty based on known prognostic criteria. A single physician independently
      evaluated each patient and their radiographs at their latest follow-up
      appointment. RESULTS: The cohorts were well matched by age, duration of symptoms,
      severity of myelopathy (Nurick grade), and preoperative sagittal alignment (C2
      C7). Mean operative time, blood loss, and hospital stay were nearly identical.
      The mean follow-up for multilevel corpectomy and laminoplasty were 49 and 40
      months, respectively. Improvement in function averaged 1.6 Nurick grades after
      laminoplasty and 0.9 grades after multilevel corpectomy (P > 0.05). Subjective
      improvements in strength, dexterity, sensation, pain, and gait were similar for
      the two operations. The prevalence of axial discomfort at the latest follow-up
      was the same for each cohort, but the analgesic requirements tended to be greater
      for patients who underwent multilevel corpectomy. Sagittal motion from C2 to C7
      decreased by 57% after multilevel corpectomy and by 38% after laminoplasty. One
      complication (C6-C7 herniated nucleus pulposus [HNP] requiring anterior discetomy
      with fusion) occurred in the laminoplasty group. Multilevel corpectomy
      complications included progression of myelopathy, nonunion, persistent dysphagia,
      persistent dysphonia, and subjacent motion segment ankylosis. CONCLUSIONS: Both
      multilevel corpectomy and laminoplasty reliably arrest myelopathic progression in
      multilevel cervical myelopathy and can lead to significant neurologic recovery
      and pain reduction in a majority of patients. Surprisingly, the laminoplasty
      cohort tended to require less pain medication at final follow-up than did the
      multilevel corpectomy cohort. Given this and the higher prevalence of
      complications among multilevel corpectomy patients, it is believed that
      laminoplasty may be the preferred method of treatment for multilevel cervical
      myelopathy in the absence of preoperative kyphosis.

PMID- 12045514
TI  - The efficacy of magnetic resonance imaging in pediatric cervical spine clearance.
AB  - STUDY DESIGN: A retrospective chart analysis of pediatric trauma patients with
      suspected cervical spine injury was performed. OBJECTIVES: This study was
      designed to evaluate the efficacy and cost-efficiency of a magnetic resonance
      imaging (MRI) protocol for cervical spine clearance in pediatric trauma patients.
      SUMMARY OF BACKGROUND DATA: The evaluation of cervical spine injury in the
      pediatric trauma population can be difficult. In obtunded or uncooperative
      children, MRI can be valuable in defining injuries of the cervical spine not
      detected by plain radiographs and computed tomography. METHODS: In 1993, a
      protocol was instituted at a pediatric trauma center using MRI to evaluate the
      cervical spine of children who could not be cleared within 72 hours. Using the
      trauma registry from February 1989 through September 1996, children with
      suspected cervical spine injury who were intubated at the time of hospital
      admission and who remained in the intensive care unit for at least 3 days were
      identified. The patients were divided into two cohorts: a "preprotocol group" and
      a "postprotocol group," consisting of patients before or after institution of the
      MRI protocol in September 1993. Medical records were reviewed to determine the
      time to cervical spine clearance, the number of days in the intensive care unit,
      and hospital days for each group. Biostatistical analysis was performed by an
      independent professional statistician. RESULTS: Fifty-one patients in each group
      met the inclusion criteria. In the preprotocol group, 19 patients underwent MRI
      at an average of 6.8 days after admission. In the postprotocol group, 31 MRIs
      were performed at an average of 2.5 days from admission. Time to cervical spine
      clearance decreased from 5.1 days in the preprotocol group to 3.2 days in the
      postprotocol group (P = 0.003). The average intensive care unit stay decreased
      from 9.2 days in the preprotocol group to 7.3 days in the postprotocol group (P =
      0.122). The average hospital stay decreased from 20.1 days in the preprotocol
      group to 15.5 days in the postprotocol group (P = 0.106). Factoring charges for
      MRI, intensive care unit beds, and hospital beds, savings of $7,700 per patient
      were estimated. CONCLUSIONS: In obtunded and intubated pediatric trauma patients
      with suspected cervical spine injury, the clearance protocol using cervical spine
      MRI was effective and cost-efficient.

PMID- 12045515
TI  - Paraspinal muscle activities of patients with scoliosis after spine fusion: an
      electromyographic study.
AB  - STUDY DESIGN: This prospective study compared the electromyographic activities of
      paraspinal muscles between normal subjects and patients with scoliosis before and
      after spine fusion. OBJECTIVE: To investigate the functional changes of
      paraspinal muscles before and after spine fusion using surface electromyography.
      SUMMARY OF BACKGROUND DATA: Idiopathic scoliosis is a common spine deformity.
      Surgical correction followed by spine fusion is the basic method of treatment,
      but the functional changes in paraspinal muscles after spine fusion still are
      unknown. METHODS: For this study, 15 healthy subjects and 19 patients with
      idiopathic scoliosis were recruited. All 19 patients received posterior spine
      fusion from T2 to T5 to T12. The surface electromyography for normal subjects and
      for patients before and after spine fusion was recorded bilaterally along the
      thoracic and lumbar paraspinal muscles for different postures. Root mean square
      and median frequency values of electromyographic activities were used to compare
      results between normal subjects and patients with scoliosis before and after
      spine fusion. RESULTS: Electromyographic activities showed significant
      differences between normal control subjects and patients with pre- or
      postoperative scoliosis. After spine fusion, electromyography showed lower root
      mean square activity in the thoracic region and higher root mean square activity
      in the lumbar region. Patients with preoperative scoliosis showed lower median
      frequency in the thoracic region and higher median frequency in the lumbar region
      than normal subjects and patients with postoperative scoliosis. The group with
      preoperative scoliosis showed the least symmetrical paraspinal muscle activity,
      followed by the postoperative and normal groups. CONCLUSIONS: Patients with
      scoliosis present unbalanced electromyographic activity in the paravertebral
      muscles, which is diminished by spine fusion, but does not return to the values
      found in normal subjects. The paraspinal muscles in the thoracic region showed
      lower activity after spine fusion, probably because of atrophy. Higher muscular
      activity was found in the lumbar region, which may lead to muscle hypertrophy.

PMID- 12045516
TI  - Natural History of Untreated Scoliosis in beta-Thalassemia.
AB  - STUDY DESIGN: A prospective study was performed. OBJECTIVES: To investigate the
      natural history of untreated scoliosis in beta-thalassemia patients in a 10-year
      period. SUMMARY OF BACKGROUND DATA: Several previous studies have demonstrated
      the bone deformities, particularly the high incidence of scoliosis, that is
      associated with beta-thalassemia. However, little is known about the evolution of
      scoliosis curvatures, and almost nothing is known about the natural history of
      this type of scoliosis and its associated lateral spinal curvatures. METHODS:
      From a group of 115 patients with beta-thalassemia who were evaluated for
      scoliosis 10 years ago, 43 patients (37%) were re-evaluated 10 years later to
      study the evolution of the untreated scoliosis and lateral spinal curvatures.
      Scoliosis, thoracic kyphosis, thoracolumbar kyphosis, and lumbar lordosis were
      measured both in the initial and last observation and were compared with each
      other. All changes in scoliosis curve location, direction, and rate of resolving,
      as well as the changes in the magnitude of the lateral spine curves, were
      recorded. RESULTS: Scoliosis curves of more than 5 degrees were present in 34
      (79%) of the 43 patients who were followed. Scoliosis progressed but was not
      statistically significant in 12% of the patients with thalassemia in a 10-year
      span. Ten years ago, 12 patients (28%) showed scoliosis of 10 degrees to 14
      degrees, whereas in the last evaluation, 15 patients (35%) had scoliosis of 10
      degrees to 19 degrees. The S-shaped scoliosis curve pattern was the most common
      (29%). In 10 years, the scoliosis curve pattern remained unchanged in 38% of the
      patients, and it changed in 38%, whereas 24% of the minor curves (5-9 degrees )
      showed spontaneous "self-resolving" character. In the last evaluation, there were
      seven patients (16%) with new cases of scoliosis de novo. There was no sex
      related predominance in prevalence of scoliosis in this series. There was a
      significant skeletal mature retardation in the patients with beta-thalassemia.
      There was a significant increase of thoracic and thoracolumbar kyphosis and a
      decrease of lumbar lordosis. The changes in the sagittal profile were not
      correlated to scoliosis in this group of patients. CONCLUSIONS: Scoliosis in beta
      thalassemia appeared with increased prevalence but with small curves of 5 degrees
      to 19 degrees that did not need active orthopedic treatment. However, a few cases
      progressed to curves less than 20 degrees, and only one patient (2.9%) showed a
      severe curve that showed much progression. The behavior of scoliosis in beta
      thalassemia differs significantly from that in idiopathic scoliosis. The skeletal
      disorders that are caused by this hematologic dysfunction seem to be responsible
      for the spinal deformities and their evolution.

PMID- 12045517
TI  - Growth patterns in children with congenital vertebral anomaly.
AB  - STUDY DESIGN: Height and weight data in children with congenital vertebral
      anomaly, recorded routinely during clinical follow-up, were analyzed. OBJECTIVES:
      To determine whether these children are significantly deficient in growth or show
      an abnormality of maturation. SUMMARY OF BACKGROUND DATA: Structural
      abnormalities in the vertebral column, and surgery to prevent or correct
      deformity secondary to this, clearly have the potential to affect the
      individual's final height. It is not clear, however, whether this is the whole
      problem, or whether there are other factors to be considered. METHODS: The height
      and weight of patients with all forms of spinal deformity are routinely recorded
      at outpatient visits. Data from patients with congenital vertebral abnormalities
      were analyzed and compared with the national standards. To test the possibility
      that the observed short stature might be familial, family groups (parents and
      siblings of patients) were invited to be measured. RESULTS: At the end of growth,
      patients with congenital vertebral anomalies were smaller than average and also
      smaller than their parents and siblings. This was more marked in girls and in the
      presence of associated anomalies, especially when multiple, as in VACTERL
      association (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb
      anomalies). It was also exacerbated by surgery, which had a demonstrable stunting
      effect on the spine. DISCUSSION: Although shortening of the spine was
      demonstrated in patients with prior spinal surgery, the contributions of the fact
      of surgery and the presumed severity of anatomic abnormality could not be
      differentiated. The observations that, even without surgery, girls were generally
      on a lower percentile than boys and that both have a tendency to lose height at
      growth spurt invite further investigation. CONCLUSIONS: The shortening of the
      spine by surgery is not a contraindication to treatment, because a straight,
      balanced spine must always be preferable to a longer, crooked and unbalanced one.
      However, it is another facet to be remembered when considering the management
      plan of the whole child.

PMID- 12045518
TI  - Histologic analysis of neural elements in the human sacroiliac joint.
AB  - STUDY DESIGN: The posterior ligament of the human sacroiliac joint was examined
      for nerves and nerve endings using histologic and immunohistochemical techniques.
      OBJECTIVE: To identify nerve fibers and mechanoreceptors in the posterior
      ligament. SUMMARY OF BACKGROUND DATA: According to the findings of previous
      studies, the human sacroiliac joint receives myelinated and unmyelinated axons
      that presumably conduct pain and proprioceptive impulses derived from
      mechanoreceptors and free nerve endings in the human sacroiliac joint. METHODS:
      Tissue obtained from six patients was stained with gold chloride and that
      obtained from six additional patients was stained using antibodies specific for
      substance P and protein gene product 9.5. RESULTS: The staining of joint tissue
      using the gold chloride technique showed myelinated and unmyelinated nerve
      fibers, two morphotypes of paciniform encapsulated mechanoreceptors, and a single
      nonpaciniform mechanoreceptor. Analysis using immunohistochemical staining for
      protein gene product 9.5 did not unequivocally show axons, nerve fascicles, or
      mechanoreceptors. Similarly, analysis based on immunohistochemical staining for
      substance P, one of several neurotransmitters known to signal pain from the
      periphery, showed reactive elements that may have been nerves, but because of
      background staining, could not be positively identified as such. CONCLUSIONS: The
      presence of nerve fibers and mechanoreceptors in the sacroiliac ligament
      demonstrates that the central nervous system receives information, certainly
      proprioceptive, and possibly pain from the sacroiliac joint. Although it is not
      known how the central nervous system uses such information, it seems reasonable
      to speculate that the proprioceptive information is used to optimize upper body
      balance at this joint. In addition, because the staining techniques used
      generally to show nerves and nerve elements in periarticular connective tissue
      are nonspecific, the distinction between neural and nonneural should be made on
      the basis of both morphologic and staining characteristics.

PMID- 12045519
TI  - The contribution of aerobic fitness and back strength to lift capacity.
AB  - STUDY DESIGN: This study used a concurrent validation design with 45 healthy
      female participants. OBJECTIVE: To measure the relative contributions of aerobic
      capacity and back strength to lift capacity. SUMMARY OF BACKGROUND DATA: This was
      the first concurrent study of the relations among spine strength, aerobic
      capacity, and lift capacity. Previous research had demonstrated moderate to
      strong relations between spine strength and lift capacity and between aerobic
      capacity and lift capacity. METHODS: Multiple regression techniques were used on
      reliable and valid measures of each construct to study the individual and joint
      contributions of spine strength and aerobic capacity to lift capacity. RESULTS:
      Both spine strength and aerobic capacity make significant independent
      contributions to lift capacity, accounting for 11% and 27% of the variance,
      respectively. Taken together, the predictive power of these variables on lift
      capacity accounts for 43% of the variance. CONCLUSIONS: Lift capacity is
      dependent on both back strength and aerobic capacity. It may be inappropriate to
      use lift capacity as an indicator for the severity of spine impairment in a
      disability determination system without taking into account the individual's
      aerobic capacity. Treatment intended to improve the lift capacity of persons with
      spine impairment should anticipate that improvement in both back strength and
      aerobic capacity will improve lift capacity.

PMID- 12045520
TI  - Simplifying outcome measurement: evaluation of instruments for measuring outcome
      after fusion surgery for chronic low back pain.
AB  - STUDY DESIGN: A comparative evaluation of outcome instruments and global
      assessment was performed. OBJECTIVE: To test patient global assessment as a
      substitute for the use of more comprehensive outcome instruments in treatment
      trials of chronic low back pain. SUMMARY OF BACKGROUND DATA: Treatment outcome
      can be measured with pain scales and functional instruments. In the absence of a
      gold standard, the patient him- or herself is the basic reference for outcome,
      for which the instruments give a more or less exact measurement. Global
      assessment, which is a retrospective recording, may overestimate improvement as a
      result of recall or motivational bias. METHODS: In this study, 294 patients
      treated for chronic low back pain were evaluated with a visual analog scale for
      back pain, the Oswestry Disability Index, the Million Score and general function
      score for disease-specific disability, and the Zung Depression Scale for
      depressive symptoms. The correlation between the pretreatment and posttreatment
      scores for the outcome instruments (Delta scores) and the global assessment
      scores was calculated; effect sizes were compared; sensitivity and specificity
      with receiver operating characteristics (ROC) curves were estimated; and
      associations of global assessment with pretreatment and posttreatment scores were
      determined. RESULTS: All the Delta scores showed significant correlations with
      patient global assessment and with each other. The effect size of global
      assessment tended to be greater than that of the outcome instruments. The
      specificity and sensitivity of the disability instruments and pain scale were
      approximately 75%, whereas they were lower for depression. The associations
      between global assessment and outcome instrument scores did not produce evidence
      that global assessment was biased. CONCLUSION: Patient global assessment is a
      valid and responsive descriptor of overall effect in randomized controlled trials
      of treatment for chronic low back pain.

PMID- 12045521
TI  - Characteristics of patients with chronic low back pain selected for surgery: a
      comparison with the general population reported from the Swedish lumbar spine
      study.
AB  - STUDY DESIGN: A group of surgical candidates with chronic low back pain was
      compared with a random sample of the general population. OBJECTIVES: To compare
      the sociodemographic, physical, and psychological characteristics of patients
      enrolled in a randomized trial of fusion surgery for chronic low back pain with
      those of an age- and gender-matched general population, and to assess whether the
      results of the current study can be generalized to other groups of subjects with
      chronic low back pain. SUMMARY OF BACKGROUND DATA: The patients with low back
      pain in industry, primary care, and rehabilitation clinics are well described,
      with evidence of increased psychological distress, social disturbance, and
      occupational dissatisfaction. The characteristics of surgical candidates with
      chronic low back pain are less well described and not compared with the general
      population. METHODS: Social, occupational, psychological, and physical data from
      self-administered questionnaires completed by 294 consecutive surgical candidates
      with chronic low back pain were compared with the same data from 278 subjects in
      an age- and gender-matched random sample of the Swedish general population. Data
      were analyzed with the general population sample divided in two subgroups:
      subjects with and those without back pain. RESULTS: The surgical candidates with
      chronic low back pain differed significantly from the control subjects free of
      back pain by demonstrating more smoking, general morbidity, and depressive
      symptoms as well as heavier occupation and self-assessed workload. However, they
      did not differ from the control subjects with back pain in these respects. In a
      multiple logistic regression analysis, physical disability was the only variable
      that independently discriminated between all three groups. The groups did not
      differ in terms of depressive symptoms. Differences were more obvious between the
      two general population groups than between the two groups with back pain. The
      rate of major depression was lower (9%) among the surgical candidates than in
      other reported groups with chronic low back pain. CONCLUSIONS: The surgical
      candidates in the current study resembled the average Swedish citizen with back
      pain. Although selected for treatment because of symptom severity, they did not
      otherwise differ substantially from the general population with back pain. On the
      contrary they unexpectedly were affected only a little by depressive symptoms,
      distinguishing them from patients with chronic low back pain in pain clinics and
      rehabilitation centers. Therefore, the results of the this outcome study are not
      generally applicable to every patient with chronic low back pain.

PMID- 12045522
TI  - Point of view.

PMID- 12045523
TI  - Three-question depression screener used for lumbar disc herniations and spinal
      stenosis.
AB  - STUDY DESIGN: A depression screener was used to determine positive responses
      amongst patients with two disorders commonly treated with surgery. OBJECTIVE: To
      examine the relation between positive responses to the depression screener and
      pain characteristics, sociodemographic responses, and Short-Form 36-Item Health
      Survey subscale scores among patients with lumbar disc herniation or spinal
      stenosis. SUMMARY OF BACKGROUND DATA: Numerous studies have reported a
      correlation between depression and low back pain, but few have examined this
      relation among patients with a diagnosis of sciatica from lumbar disc herniation
      or spinal stenosis. The Health Status Questionnaire 2.0 includes both the Short
      Form 36-Item Health Survey (a validated, multidimensional, generic instrument
      measuring health-related quality of life and functional status) and the three
      question depression screener. METHODS: The database of the National Spine Network
      (a nonprofit collaboration of physicians caring for patients with back and neck
      problems that pools patient data) was queried for patients 18 to 65 years of age
      with a diagnosis of lumbar disc herniation (n = 2878) and patients 30 to 80 years
      of age with a diagnosis of spinal stenosis (n = 3801). Depression screeners
      scored positive when patients reported depressive symptoms within the year to any
      question about symptoms. RESULTS: The screener elicited positive responses from
      36.4% of the patients with spinal stenosis and 38.4% of the patients with lumbar
      disc herniation. Among the patients with spinal stenosis or lumbar disc
      herniation, those with positive depression screener responses reported longer
      duration of symptoms (>7 weeks) and failure to improve. They were more likely to
      be obese, recipients of workers' compensation, unmarried, and less educated
      (below Grade 12). In multivariate analyses, positive depression screener
      responses were significantly associated with an attorney's services and a longer
      duration of symptoms. CONCLUSIONS: A positive depression screener response is
      strongly associated with poorer functional status and health-related quality of
      life, as measured by the Short-Form 36-Item Health Survey, among patients with
      lumbar disc herniation or spinal stenosis, and higher symptom intensity.

PMID- 12045524
TI  - Point of view.

PMID- 12045525
TI  - The effect of different standing and sitting postures on trunk muscle activity in
      a pain-free population.
AB  - STUDY DESIGN: A normative, single-group study was conducted. OBJECTIVE: To
      determine whether there is a difference in electromyographic activation of
      specific lumbopelvic muscles with the adoption of common postures in a pain-free
      population. SUMMARY OF BACKGROUND DATA: Clinical observations indicate that
      adopting passive postures such as sway standing and slump sitting can exacerbate
      pain in individuals with low back pain. These individuals often present with poor
      activation of the lumbopelvic stabilizing musculature. At this writing, little
      empirical evidence exists to document that function of the trunk and lumbopelvic
      musculature are related to the adoption of standardized standing and sitting
      postures. METHODS: This study included 20 healthy adults, with equal
      representation of the genders. Surface electromyography was used to measure
      activity in the superficial lumbar multifidus, internal oblique, rectus
      abdominis, external oblique, and thoracic erector spinae muscles for four
      standardized standing and sitting postures. RESULTS: The internal oblique,
      superficial lumbar multifidus, and thoracic erector spinae muscles showed a
      significant decrease in activity during sway standing (P = 0.027, P = 0.002, and
      P = 0.003, respectively) and slump sitting (P = 0.007, P = 0.012, and P = 0.003,
      respectively), as compared with erect postures. Rectus abdominis activity
      increased significantly in sway standing, as compared with erect standing (P =
      0.005). CONCLUSIONS: The findings show that the lumbopelvic stabilizing
      musculature is active in maintaining optimally aligned, erect postures, and that
      these muscles are less active during the adoption of passive postures. The
      results of this study lend credence to the practice of postural retraining when
      facilitation of the lumbopelvic stabilizing musculature is indicated in the
      management of specific spinal pain conditions.

PMID- 12045526
TI  - New technologies in spine: nucleus replacement.
AB  - Nucleus replacement offers several benefits over other surgical options. Several
      design criteria need to be met. Nucleus prostheses can be either preformed or
      formed in situ. Preclinical evaluations should include biomechanical testing,
      biocompatibility testing, and surgical technique evaluation. Indications and
      contraindications of nucleus prosthesis are largely determined by the benefit-to
      risk ratio and benefit-to-cost ratio.

PMID- 12045527
TI  - Letters.

PMID- 12045528
TI  - Roentgenographic findings in the cervical spine in asymptomatic persons: A 10
      year follow-up.

PMID- 12045529
TI  - An unusual presentation of a lumbar synovial cyst: case report.
AB  - STUDY DESIGN: A case of intraforaminal synovial cyst is reported. OBJECTIVES: To
      stress the importance of the way intraforaminal synovial cyst, a very rare
      condition, causes a peculiar position of the nerve root in the foramen and to
      describe the required surgical approach. SUMMARY OF BACKGROUND DATA:
      Intraforaminal synovial cyst is a highly unusual finding. The existence of this
      rare entity raises the problem of differential diagnosis with other space
      occupying lesions of the neural foramen, such as herniated disc, neurinoma,
      neurofibroma, and metastatic lesions METHODS AND RESULTS: A 64-year-old woman
      suffered a right L4 radiculopathy with motor deficit. Computed tomography showed
      a space-occupying lesion in the L4-L5 foramen isodense with the disc. Magnetic
      resonance images showed a right intraforaminal cystic lesion at the L4-L5 level
      with no enhancement after intravenous infusion of gadolinium. A 3-cm cystic
      lesion, which appeared to arise from the L4-L5 facet joint without direct
      communication, was excised from the L4-L5 foramen. In contrast with
      intraforaminal disc herniation, downward displacement of the L4 nerve root was
      observed. Two months after surgery, the patient was pain-free and neurologic
      examination revealed no motor deficit. CONCLUSIONS: An unusual intraforaminal
      presentation of a lumbar synovial cyst demonstrates the importance of considering
      this entity and of adapting the surgical technique to avoid injury to the nerve
      root.

PMID- 12045530
TI  - Rapid, symptomatic enlargement of a lumbar juxtafacet cyst: case report.
AB  - STUDY DESIGN: A case is reported in which a 45-year-old man developed cauda
      equina syndrome caused by enlargement of an L4-L5 juxtafacet cyst diagnosed 4
      months earlier. OBJECTIVES: To highlight the short interval that can elapse
      between the discovery of a juxtafacet cyst and its remarkable progression.
      SUMMARY OF BACKGROUND DATA: Although juxtafacet cysts are acquired lesions, how
      long they take to develop remains unclear. Hemorrhage is a well-known cause of
      rapid or even dramatic cyst enlargement. This is the first report providing
      magnetic resonance imaging evidence of rapid, remarkable enlargement of a
      nonhemorrhagic juxtafacet cyst. METHODS: The patient underwent conservative
      treatment for an L4-L5 right juxtafacet cyst diagnosed by magnetic resonance
      imaging during evaluation of posttraumatic lower back pain. Four months later,
      the patient presented with severe pain radiating down the right lateral leg,
      urinary retention, and impaired dorsal flexion of the right foot. Repeat magnetic
      resonance imaging showed the cyst now markedly enlarged and occupying almost the
      entire width of the canal. RESULTS: The cyst was removed, and the patient's
      symptoms abated. At 15 months after surgery, he is symptom-free. CONCLUSIONS:
      Juxtafacet cyst may occasionally enlarge and cause severe symptoms within months.

PMID- 12045531
TI  - Nonteratomatous tumors in the pediatric sacral region.
AB  - STUDY DESIGN: Two institutional experiences in nonteratomatous sacral tumors of
      the child were analyzed retrospectively. OBJECTIVES: To examine noncongenital
      nonteratomatous sacral tumors, which are more common in older infants and, as a
      group, are rare. SUMMARY OF BACKGROUND DATA: Pediatric sacral tumors usually
      occur in the newborn period, with most of these tumors being sacrococcygeal
      teratomas. Other common benign congenital tumors of the sacrum include lipomas,
      dermoids, and epidermoids. METHODS: Six patients were found in a 6-year period.
      Four patients underwent posterior resection of their tumors. One underwent a
      combined anterior and posterior approach. One patient underwent a posterior
      resection and will undergo a second stage anterior approach later to allow for
      chemotherapy and radiation to shrink the intrapelvic portion of the tumor.
      RESULTS: Ages ranged from 8 to 11 years. Three were males, and three were
      females. Five of six presented with back pain, three had constipation, and two
      had gait difficulties. Pathologies were diverse. They included ganglioneuroma (n
      = 1), myxopapillary ependymoma (n = 2), primitive neuroectodermal tumor (n = 1),
      aneurysmal bone cyst (n = 1), and Ewing's sarcoma (n = 1). No progression of
      disease has occurred in the follow-up period of 1.5 to 7 years (average, 5
      years). Radical resection did not result in instability. CONCLUSIONS: In
      contradistinction to adults, in whom chordomas and metastases are the most common
      primary and secondary tumors, the pediatric group does not have a predominant
      pathology. Tumors may attain extremely large sizes and may be very vascular.
      Multiple therapeutic methods may be required, including adjuvant chemotherapy
      and, possibly, embolization. Because of the wide range of pathologies, prognosis
      is varied.

PMID- 12045532
TI  - Treatment of severe postburn kyphosis with combined plastic surgery and milwaukee
      bracing.
AB  - STUDY DESIGN: A case is reported in which severe postburn kyphosis is treated
      with combined plastic surgery and Milwaukee bracing. OBJECTIVES: To demonstrate
      that severe kyphosis can develop secondary to burn scars and that spine surgery
      can be avoided. SUMMARY OF BACKGROUND DATA: Nothing is available in the
      literature on this subject. METHODS: A 14-year-old boy had severe burns of the
      arms, anterior neck, and anterior torso with a resulting 90 degrees stiff
      kyphosis. RESULTS: The patient was treated by multiple plastic surgery procedures
      combined with a Milwaukee brace, which corrected his kyphosis to a normal
      alignment. CONCLUSIONS: Spine surgery was avoided with quality plastic surgery
      and Milwaukee brace management.

PMID- 12045533
TI  - Paradoxical air embolism from patent foramen ovale in scoliosis surgery.
AB  - STUDY DESIGN: A case was reported in which paradoxical air embolism arose from
      the patent foramen ovale in scoliosis surgery. OBJECTIVES: To present a case of
      suspected paradoxical air embolism after scoliosis surgery. SUMMARY OF BACKGROUND
      DATA: Embolic accident during scoliosis surgery may be caused by air, thrombus,
      or fat. There is growing attention on patent foramen ovale involved in
      paradoxical embolism. The devastating consequences are caused by multiple artery
      occlusions. METHODS: Details of a recent documented neurologic complication
      (paraplegia, weakness of right arm, and blurry vision) after scoliosis surgery
      have been analyzed in medical publications. RESULTS: The surgical procedure was
      not imputed. The causative role of epidural catheter for analgesia was
      considered, but it is likely that a paradoxical embolism occurred in this case,
      based on the multifocal (cerebral and spinal) neurologic dysfunction, the
      evidence of cerebral ischemia (on computed tomography), and the presence of a
      patent foramen ovale (on postoperative transesophageal echocardiography).
      Although no intraoperative embolism detection was available, air embolism was
      highly suspected because there was no absolute argument to exclude cruor or fatty
      embolism. CONCLUSIONS: It is critical to detect a patent foramen ovale before
      surgery and cerebral embolization intraoperatively. This might permit
      ascertainment of the etiologic diagnosis in case of a complication in surgery for
      scoliosis.

PMID- 12045534
TI  - Surgical treatment of migraine headaches.
AB  - This prospective study was conducted to investigate the role of removal of
      corrugator supercilii muscles, transection of the zygomaticotemporal branch of
      the trigeminal nerve, and temple soft-tissue repositioning in the treatment of
      migraine headaches. Using the criteria set forth by the International Headache
      Society, the research team's neurologist evaluated patients with moderate to
      severe migraine headaches, to confirm the diagnosis. Subsequently, the patients
      completed a comprehensive migraine headaches questionnaire and the team's plastic
      surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator
      supercilii muscle. The patients were asked to maintain an accurate diary of their
      migraine headaches and to complete a monthly questionnaire documenting pertinent
      information related to their headaches. Patients in whom the injection of Botox
      resulted in complete elimination of the migraine headaches then underwent
      resection of the corrugator supercilii muscles. Those who experienced only
      significant improvement underwent transection of the zygomaticotemporal branch of
      the trigeminal nerve with repositioning of the temple soft tissues, in addition
      to removal of the corrugator supercilii muscles. Once again, patients kept a
      detailed postoperative record of their headaches. Of the 29 patients included in
      the study, 24 were women and five were men, with an average age of 44.9 years
      (range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001)
      reported a positive response to the injection of Botox, 16 (55.2 percent, p <
      0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced
      significant improvement (at least 50 percent reduction in intensity or severity),
      and five (17.2 percent, not significant) did not notice a change in their
      migraine headaches. Twenty-two of the 24 patients who had a favorable response to
      the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001)
      observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01)
      reported elimination of migraine headaches and 11 patients (50.0 percent, p <
      0.004) noted a considerable improvement. For the entire surgical group, the
      average intensity of the migraine headaches reduced from 8.9 to 4.1 on an
      analogue scale of 1 to 10, and the frequency of migraine headaches changed from
      an average of 5.2 per month to an average of 0.8 per month. For the group who
      only experienced an improvement, the intensity fell from 9.0 to 7.5 and the
      frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent,
      not significant) did not notice any change. The follow-up ranged from 222 to 494
      days, the average being 347 days. In conclusion, this study confirms the value of
      surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited
      significantly from the surgery. It is also evident that injection of Botox is an
      extremely reliable predictor of surgical outcome.

PMID- 12045535
TI  - The use of recombinant erythropoietin in the reduction of blood transfusion rates
      in craniosynostosis repair in infants and children.
AB  - The vast majority of infants and children undergoing craniosynostosis correction
      receive a blood transfusion. The risks of blood transfusion include, but are not
      limited to, acute hemolytic reactions (approximately 1 of 250,000), human
      immunodeficiency virus (approximately 1 of 200,000), hepatitis B and C
      (approximately 1 of 30,000 each), and transfusion-related lung injuries
      (approximately 1 of 5000). This prospective, single-blinded, randomized study was
      undertaken to examine the safety and efficacy of preoperative single weekly
      dosing with erythropoietin (epoetin alfa) in reducing the rate of transfusion in
      infants and small children undergoing craniosynostosis repair. A total of 29
      patients (<8 years) undergoing craniosynostosis repair were randomized into two
      groups: one received preoperative erythropoietin (600 U/kg) weekly for 3 weeks,
      and the other served as a control. All caregivers responsible for blood
      transfusions were blinded, and strict criteria for transfusion were established.
      A pediatric hematologist monitored both groups, and all patients received
      supplemental iron (4 mg/kg). Fourteen patients were randomized to receive
      erythropoietin, and eight of these 14 patients (57 percent) required transfusion
      (mean age, 17 months; mean weight, 10.1 kg). Of the six patients not requiring
      transfusion, three were younger than 12 months old (mean, 6 months). Fourteen of
      15 patients (93 percent) in the control group (mean age, 13 months; mean weight,
      9.3 kg) required a blood transfusion during the study. The only control patient
      not requiring transfusion was the eldest (5 years old). The difference between
      the two groups was statistically significant (Fisher's exact test = 0.03). The
      control group showed no change in hemoglobin levels from baseline to preoperative
      levels, but the erythropoietin group increased their average hemoglobin levels
      from 12.1 to 13.1 g/dl. There were no adverse effects noted among children
      receiving erythropoietin, nor were there any surgical complications. The authors
      conclude that the preoperative administration of erythropoietin significantly
      raised hemoglobin levels and reduced the need for a blood transfusion with
      craniosynostosis correction. More suggestions are made that may further reduce
      the need for blood transfusions, and a cost-benefit analysis is discussed.

PMID- 12045536
TI  - Venous drainage architecture of the temporal and parietal regions: anatomy of the
      superficial temporal artery and vein.
AB  - Anatomy of the superficial temporal artery and vein was analyzed with
      arteriograms, venograms, and arteriovenograms of fresh cadavers that had been
      injected with contrast medium. The superficial temporal artery always divided
      into two major branches: the frontal and parietal branches. However, the
      superficial temporal vein divided into one, two, or three major branches. The
      distribution area of the major branches of the superficial temporal vein was
      larger than that of major branches of the superficial temporal artery, and
      arteriovenograms clearly demonstrated that, except for its proximal portion, the
      superficial temporal vein was independent of the superficial temporal artery. The
      frontal and parietal branches of the superficial temporal artery had thin venae
      comitantes that originated from the proximal portion of the superficial temporal
      vein, and the venae comitantes gave off branches toward the skin and the
      underlying soft tissue. Branches to the skin anastomosed with a superficial
      venous network in the skin layer, which was formed by ramifications of the
      superficial temporal vein. The venous architecture of the temporal and parietal
      regions consisted of cutaneous veins and venae comitantes and was basically
      similar to that of the forearm and scapular region.

PMID- 12045537
TI  - An anatomic study and clinical applications of the reversed submental perforator
      based island flap.
AB  - The authors present their experience with the reversed submental perforator-based
      island flap for nose reconstruction and their anatomic and clinical studies.
      There have been several descriptions on the reversed pattern of the submental
      flap, but its anatomic background and clinical availability are still
      questionable. The submental area was analyzed by anatomic dissection on four
      fresh cadavers that were injected with a barium mixture. The anatomic data were
      accumulated with the authors' clinical experience with eight patients treated
      with a submental island flap. On the basis of these studies, the location of
      reliable perforators was constant at the lateral and/or medial border of the
      anterior belly of the digastric muscle, but their locations were not always
      symmetric on both sides in the submental territory. Unlike the comitant submental
      vein, another larger superficial vein has a different course before reaching the
      lateral border of the anterior digastric belly, and therefore, it must be
      included in the reversed flap. The premised anatomic results and the clinical
      experience prove the reliability of the reversed submental perforator-based
      island flap as a versatile option in midface reconstruction, including the nose,
      once the dissection has been carefully done, respecting the anatomic points that
      can be found in this study.

PMID- 12045538
TI  - Technique and strategy in anterolateral thigh perforator flap surgery, based on
      an analysis of 15 complete and partial failures in 439 cases.
AB  - The free anterolateral thigh flap is becoming one of the most preferred options
      for soft-tissue defect reconstruction. Between June of 1996 and August of 2000,
      672 anterolateral thigh flaps were used in 660 patients in Chang Gung Memorial
      Hospital. A total of 439 flaps were cutaneous or fasciocutaneous flaps based on
      musculocutaneous perforators. The analysis of the flap failures was done only in
      this perforator series. In six cases, no suitable skin vessel was found during
      the dissection of the flaps. The complete success rate was 96.58 percent (424 of
      439). Of the 15 failure cases, eight were complete and seven were partial (10
      percent to 60 percent of the flap). Thirty-four flaps were reexplored, and 19 (56
      percent) were salvaged. In this study, some of the reasons for the flap failure,
      unique to the anterolateral thigh perforator flap, were identified. They include
      inadvertent division of perforator at the fascial plane as a result of inadequate
      knowledge of perforator anatomy, inadvertent injury to the perforator during
      intramuscular dissection (noted by the surgeon or ignored) as a result of
      inexperience, and twisting of the pedicle during inset of the flap at the
      recipient site. Technical pearls in the harvest of the anterolateral thigh
      perforator flap are as follows: mapping of the skin vessels with a Doppler probe
      before flap design, meticulous dissection of the perforator under surgical loupe
      or even lower-magnification microscope, inclusion of a small fascia cuff around
      the perforator, and intermittent topical use of Xylocaine during the
      intramuscular dissection of the perforators. During reexploration, one must
      search for twisting of the pedicle and small bleeders from the branches of the
      intramuscular perforators.

PMID- 12045540
TI  - Have we found an ideal soft-tissue flap? An experience with 672 anterolateral
      thigh flaps.
AB  - The free anterolateral thigh flap is becoming one of the most preferred options
      for soft-tissue reconstruction. Between June of 1996 and August of 2000, 672
      anterolateral thigh flaps were used in 660 patients at Chang Gung Memorial
      Hospital. Four hundred eighty-four anterolateral thigh flaps were used for head
      and neck region recontruction in 475 patients, 58 flaps were used for upper
      extremity reconstruction in 58 patients, 121 flaps were used for lower extremity
      reconstruction in 119 patients, and nine flaps were used for trunk reconstruction
      in nine patients. Of the 672 flaps used in total, a majority (439) were
      musculocutaneous perforator flaps. Sixty-five were septocutaneous vessel flaps.
      Of these 504 flaps, 350 were fasciocutaneous and 154 were cutaneous flaps. Of the
      remaining 168 flaps, 95 were musculocutaneous flaps, 63 were chimeric flaps, and
      the remaining ten were composite musculocutaneous perforator flaps with the
      tensor fasciae latae. Total flap failure occurred in 12 patients (1.79 percent of
      the flaps) and partial failure occurred in 17 patients (2.53 percent of the
      flaps). Of the 12 flaps that failed completely, five were reconstructed with
      second anterolateral thigh flaps, four with pedicled flaps, one with a free
      radial forearm flap, one with skin grafting, and one with primary closure. Of the
      17 flaps that failed partially, three were reconstructed with anterolateral thigh
      flaps, one with a free radial forearm flap, five with pedicled flaps, and eight
      with primary suture, skin grafting, and conservative methods. In this large
      series, a consistent anatomy of the main pedicle of the anterolateral thigh flap
      was observed. In cutaneous and fasciocutaneous flaps, the skin vessels
      (musculocutaneous perforators or septocutaneous vessels) were found and followed
      until they reached the main pedicle, regardless of the anatomic position. There
      were only six cases in this series in which no skin vessels were identified
      during the harvesting of cutaneous or fasciocutaneous anterolateral thigh flaps.
      In 87.1 percent of the cutaneous or fasciocutaneous flaps, the skin vessels were
      found to be musculocutaneous perforators; in 12.9 percent, they were found as
      septocutaneous vessels. The anterolateral thigh flap is a reliable flap that
      supplies a large area of skin. This flap can be harvested irrespective of whether
      the skin vessels are septocutaneous or musculocutaneous. It is a versatile soft
      tissue flap in which thickness and volume can be adjusted for the extent of the
      defect, and it can replace most soft-tissue free flaps in most clinical
      situations.

PMID- 12045542
TI  - First-line treatment of deep sternal infection by a plastic surgical approach:
      superior results compared with conventional cardiac surgical orthodoxy.
AB  - A majority of cardiac surgeons manage deep sternal infection with sternal wound
      debridement, rewiring, and closed drainage, with or without antibiotic saline
      tube irrigation (the traditional approach). The authors' experience with the
      traditional approach was unsatisfactory; therefore, they undertook a radical
      change in management: an immediate plastic surgical approach. Hence, deep sternal
      infection was managed by immediate debridement followed by a bilateral pectoralis
      major myocutaneous advancement flap with greater omental transposition (PMOFR).
      This is the first such study reporting the effect of this strategy on the rate of
      eradication of deep sternal infection, intensive care unit stay, total hospital
      length of stay, major complications, mortality, intermediate survival, and
      patient satisfaction, as compared with the traditional approach used by cardiac
      surgeons at the authors' institution. All patients who developed a deep sternal
      infection from 1993 through 1998 at a tertiary teaching hospital were included.
      In the PMOFR group (nine patients), after a diagnosis of clinical sternal wound
      infection, debridement was performed immediately, either if sternal dehiscence
      occurred or in the absence of clinical dehiscence, if the patient or the
      sternotomy wound did not clinically improve with medical therapy within 48 hours
      from suspected diagnosis. Open irrigation and packing for 2 to 4 days was
      followed by treatment with a PMOFR. In the group treated using the traditional
      approach (12 patients), no predetermined plan was present. Thus, at the cardiac
      surgeon's discretion, wound debridement was undertaken, followed by closed
      drainage (three patients), closed tube irrigation (six patients), and open
      granulation with delayed plastic surgery (three patients). The incidence of major
      complications (PMOFR, 22 percent; traditional approach, 92 percent; p = 0.001),
      intensive care unit readmission (PMOFR, 0 percent; traditional approach, 58
      percent; p = 0.005), total hospital length of stay (PMOFR, 32 days; traditional
      approach, 79 days; p = 0.001), reoperation rates (PMOFR, 0 percent; traditional
      approach, 100 percent; p = 0.001) and in-hospital 30-day mortality rate (PMOFR, 0
      percent; traditional approach, 33 percent; p = 0.05) were superior in the PMOFR
      group. At a mean follow-up of 2 years, freedom from recurrence of the infection
      (PMOFR, 100 percent; traditional approach, 11.5 percent; p = 0.005) and overall
      survival rate (PMOFR, 100 percent; traditional approach, 50 percent; p = 0.005)
      were also superior with PMOFR. A majority of patients in the PMOFR group (90
      percent) had no functional or cosmetic complaints secondary to the procedure.A
      predetermined plan of immediate debridement followed by treatment with PMOFR
      rapidly, reliably, and effectively eradicated deep sternal infection. This
      translated to reduced length of stay and need for additional surgery, improved
      survival, and excellent intermediate freedom from deep sternal infection, with
      minimal patient dissatisfaction. The traditional approach to managing deep
      sternal infection was thus abandoned.

PMID- 12045543
TI  - Air dissipation in saline breast implants.
AB  - Residual air within saline breast implants can cause patient discomfort due to
      the mechanical and auditory effects of sloshing. Small amounts of air have no
      clinical significance, but if larger quantities are present and audible, the
      patient is reassured that the implant shell is gas-permeable and that the air
      will dissipate/diffuse. This study examined the time necessary for air
      dissipation in saline breast implants.Twelve McGhan style #68 saline breast
      implants were divided into two groups: group A, which included six implants with
      a size of 240 cc, and group B, which included six implants with a size of 270 cc.
      The implants were filled with room-temperature, intravenous, normal saline to
      their designated volumes, plus 30 cc of overfill. All air was evacuated, and each
      implant was inoculated with 5 cc of air. The implants were then submerged in a
      single tank of normal saline at 37 degrees C, at a depth of 20.4 cm to replicate
      capillary pressure. Intragroup analysis showed the air bubble was absent in group
      A at an average of 35.3 days (variance = 4.13) and in group B at an average of
      38.0 days (variance = 0). If audible intraluminal air is present in the clinical
      setting, the patient can be reassured that the problem will resolve in
      approximately 30 days or less.

PMID- 12045544
TI  - Microbial growth in saline breast implants and saline tissue expanders.
AB  - The subject of microbial growth within the saline medium of prosthetic breast
      implants has been one of great controversy in recent years. Although several
      articles have described microbial growth within the tissue surrounding implanted
      breast prostheses, few have attempted to determine the possibility of such
      contamination of the luminal saline. The authors studied the intraluminal saline
      medium of a series of explanted breast prostheses with the objective of
      identifying any microbial contamination. Over a 6-month period, a consecutive
      series of saline-filled breast implants and tissue expanders were removed from 37
      patients. Under the supervision of a microbiologist, saline extracted from each
      implant was subjected to bacterial and fungal cultures, Gram staining, and acid
      fast staining. A total of 24 saline-filled breast implants were removed from 15
      patients, and 32 saline-filled tissue expanders were removed from 22 patients.
      The average length of implantation was 28.1 months for the implants and 7.1
      months for the expanders. None of the saline within the implants or expanders
      within our series displayed any evidence of microbial contamination. These
      results suggest that microbial contamination of the luminal saline of prosthetic
      breast implants is an extremely unlikely event.

PMID- 12045546
TI  - Ex vivo intraoperative angiography for rectus abdominis musculocutaneous free
      flaps.
AB  - In this study, the vascular architecture of rectus abdominis free flaps nourished
      by deep inferior epigastric vessels was investigated using an ex vivo
      intraoperative angiogram. Oblique rectus abdominis free flaps were elevated and
      isolated from the donor site. In 11 patients, the vascular architecture of these
      flaps was analyzed before the flap was thinned. Radiographic study identified an
      average of 2.1 large deep inferior epigastric arterial perforators in each flap.
      In nine of the 11 flaps, the axial artery was visible. In four flaps, the axial
      artery originated from the perforator of the lateral branch of the deep inferior
      epigastric artery; in five others, it originated from the medial branch. In each
      flap, the angle of the axial perforator from its anterior rectus sheath in the
      vertical plane was measured; its mean was 50.6 degrees. All flaps survived,
      although three showed partial necrosis in the distal portions. In two of these
      three flaps, the axial artery was not visible in the angiograms, and the third
      revealed a one-sided distribution of axial flap arteries. Using ex vivo
      intraoperative angiography, the architecture of the individual flap, its axial
      perforator, and its connecting axial flap vessel could be investigated. This
      information can help the surgeon safely thin and separate the flap.

PMID- 12045547
TI  - Significance of intraabdominal compartment pressures following TRAM flap breast
      reconstruction and the correlation of results.
AB  - Abdominal wall closure after transverse rectus abdominis myocutaneous (TRAM) flap
      breast reconstruction is often performed under considerable tension and may
      theoretically cause a component of abdominal compartment syndrome. This
      prospective study examined intraabdominal pressure after TRAM reconstruction and
      correlated the findings with clinical course and outcome. All patients who
      underwent pedicled TRAM flap breast reconstruction from November of 1999 to
      December of 2000 (n = 77) were included and compared with nonoperative controls
      (n = 24). Intraabdominal pressures were measured indirectly using the urinary
      catheter in the postanesthesia care unit on postoperative days 1 and 2. Outcome
      measures included vital signs, urinary output, net 24-degree fluid balance, and
      complications. The preoperative variables were age, body mass index, parity, and
      presence of an epidural. For statistical analysis, the TRAM patients were divided
      into three groups on the basis of type of closure (bipedicle, unipedicle, and
      mesh), which were compared by analysis of variance. A multivariate logistic
      regression was performed to identify risk factors for patients with
      intraabdominal pressures > or =20 mmHg who were thought to have a component of
      abdominal compartment syndrome. The incidence of complications was compared by
      chi-square, with statistical significance determined for p < 0.05. Average
      intraabdominal pressures were significantly higher in the bipedicled TRAM (14.1
      mmHg) and unipedicle TRAM (9.9 mmHg) groups when compared with the mesh group (5
      mmHg) and controls (3.7 mmHg; p < 0.001). Increased intraabdominal pressure was
      transient and peaked on postoperative day 1. Elevated pressure was associated
      with decreased urinary output, decreased net fluid balance, and increased
      respiratory rate. Patients with intraabdominal pressures > or =20 mmHg (n = 10)
      had a higher incidence of complications (60 percent) compared with patients who
      had pressures <20 mmHg (18 percent; p < 0.05). Elevated intraabdominal pressures
      were strongly associated with donor-site and general complications. Positive
      predictive factors for elevated pressure included body mass index and type of
      closure (bipedicled or bilateral). Multiple pregnancies seemed to have a
      protective effect.A transient component of abdominal compartment syndrome does
      exist after TRAM flap breast reconstruction. Bipedicle closure, nulliparous
      women, and increased body mass index were risk factors for elevated
      intraabdominal pressures. Tension-free mesh closure seemed to have a protective
      effect. Symptomatic trends and certain complications were associated with, and
      possibly explained by, an elevated intraabdominal pressure.

PMID- 12045548
TI  - Complications in postmastectomy breast reconstruction: two-year results of the
      Michigan Breast Reconstruction Outcome Study.
AB  - In this study, the effects of procedure type, timing, and other clinical
      variables on complication rates in mastectomy reconstruction were prospectively
      evaluated. Using a prospective cohort design, women undergoing first-time,
      immediate or delayed breast reconstruction were recruited from 12 centers and 23
      plastic surgeons. Complication data for expander/implant, pedicle transverse
      rectus abdominis musculocutaneous (TRAM) flap, and free TRAM flap procedures were
      evaluated 2 years after surgery in 326 patients. For each patient, the total
      number of complications was recorded and the complication data were dichotomized
      in two ways: (1) total complications and (2) major complications (those requiring
      reoperation, rehospitalization, or nonperioperative intravenous antibiotic
      treatment). The effects of procedure type, timing, radiotherapy, chemotherapy,
      age, smoking, and body mass index on complication rates were analyzed using
      logistic regression. Immediate reconstructions had significantly higher total as
      well as major complication rates, compared with delayed procedures (p = 0.011 and
      0.005, respectively). Furthermore, higher body mass indexes were associated with
      significantly higher total and major complication rates (p = 0.005 and p < 0.001,
      respectively). No significant effects on complication rates were noted for
      procedure type or for the other independent variables, although there was
      evidence of trends for higher total and major complication rates in implant
      patients who received radiotherapy and a trend for higher major complication
      rates in TRAM flap patients who received chemotherapy. It was concluded that (1)
      immediate reconstructions were associated with significantly higher complication
      rates than delayed procedures, and (2) procedure type had no significant effect
      on complication rates.

PMID- 12045549
TI  - Periumbilical rectus abdominis perforator preservation significantly reduces
      superficial wound complications in "separation of parts" hernia repairs.
AB  - Midline ventral hernia repair with bilateral sliding myofascial rectus abdominis
      flaps, or the "separation of parts" technique, has low hernia recurrence rates.
      However, this technique, as originally described, creates massively undermined
      skin and subcutaneous tissue flaps. These undermined skin flaps can suffer
      marginal skin loss, fat necrosis, and delayed wound healing. The authors propose
      that preserving the periumbilical rectus abdominis perforators to the abdominal
      skin flaps will decrease the prevalence of postoperative superficial wound
      complications. A retrospective review of 66 consecutive, large, midline hernia
      repairs using a separation of parts technique was undertaken to identify any
      correlation between the preservation of periumbilical rectus abdominis
      perforators to the skin flaps and the prevalence of postoperative wound
      complications. In 25 cases, the standard separation of parts technique was
      performed with wide undermining of the skin and subcutaneous tissues. In 41
      cases, the modified separation of parts technique was performed with maintenance
      of the periumbilical rectus abdominis perforators to the abdominal skin flaps.
      Comparison of these two groups revealed no difference in age; sex; body mass
      index; initial hernia size on physical examination; prevalence of smoking,
      diabetes, or steroid use; or prevalence of a simultaneous intraabdominal
      procedure. A statistically significant difference was noted in postoperative
      wound complications between the two groups (p < 0.05). Of patients who underwent
      the standard separation of parts technique, five of 25 patients (20 percent) had
      wound complications as compared with one of 41 patients (2 percent) who underwent
      the modified separation of parts technique with perforator preservation. The
      postoperative hernia recurrence (7 percent and 8 percent, respectively) and
      hematoma (4 percent and 2 percent, respectively) rates were similar in both
      groups. A trend of increased wound complications was noted when separation of
      parts was combined with an intraabdominal procedure (18 percent versus 3 percent,
      p = 0.08). Interestingly, within this group, the modified separation of parts
      technique with preservation of the periumbilical rectus abdominis perforators
      demonstrated a trend of fewer wound complications as compared with the standard
      separation of parts technique (7 percent versus 31 percent, p = 0.15). The
      authors conclude that preservation of the periumbilical rectus abdominis
      perforators significantly reduces the prevalence of major postoperative
      superficial wound complications in separation of parts hernia repairs.
      Simultaneous intraabdominal procedures with separation of parts hernia repairs
      seem to increase the prevalence of wound complications. This increased prevalence
      of wound complications seems to be minimized when the modified separation of
      parts technique is performed.

PMID- 12045551
TI  - Quantitation of breast sensibility following reduction mammaplasty: a comparison
      of inferior and medial pedicle techniques.
AB  - The preservation of sensitivity within the nipple-areola complex is of paramount
      importance to patients presenting for reconstructive and aesthetic breast
      procedures. Previous attempts to measure sensation in the breast before and after
      surgery have relied primarily on the Semmes-Weinstein monofilament test, which is
      an imprecise study that measures the logarithm of force necessary to bend a
      series of six to 20 filaments. Within the last 10 years, various authors have
      published normative pressure threshold data for the breast that have varied by a
      magnitude of greater than 10-fold. Recently, precise anatomic studies have been
      performed that have elucidated the innervation of the nipple-areola complex
      medially and laterally from cutaneous branches of the intercostal nerves. Despite
      this knowledge, no quantitative sensibility studies have yet been performed that
      compare postoperative sensation when medially versus laterally innervated
      pedicles have been used in reduction mammaplasty. The present study is the first
      to use computer-assisted neurosensory testing to generate normal breast sensation
      data and to compare sensory outcomes between the inferior and the medial pedicle
      techniques of reduction mammaplasty.A total of 34 patients were divided into four
      groups and underwent breast sensory testing (67 breasts total) using the Pressure
      Specified Sensory Device, a computer-assisted force transducer that measures
      static and moving one and two-point discrimination. Sensation in the nipple and
      in the four quadrants of the areola was measured. Groups I and II were composed
      of 17 unoperated controls with breast sizes ranging from 34A to 36C (group I; 18
      breasts) and 36DD to 46EE (group II; 16 breasts) who presented to a general
      plastic surgery clinic. Groups III and IV were composed of 17 patients who
      underwent either medial or inferior pedicle reduction mammaplasty between July of
      1997 and March of 1999. Pressure thresholds in the most sensitive breasts were as
      low as 0.3 g/mm2, a marked contrast to data from previous studies using Semmes
      Weinstein monofilaments documenting the lowest recordable pressure threshold as
      greater than 2 g/mm2. Several findings from previous studies using Semmes
      Weinstein monofilament testing were confirmed in unoperated controls, including
      an inverse relationship between sensitivity and breast size, superior nipple
      sensitivity when compared with the areola, and significant interpatient
      variability with respect to static and moving two-point discrimination among
      women matched according to age and breast size. When comparing medial with
      inferior pedicle reduction mammaplasty patients, it was found that despite
      significantly greater reductions using the medial pedicle technique (mean of 1.7
      kg versus 1.1 kg of breast tissue removed), there were no significant differences
      in postoperative sensory outcomes in the sample size of 17 patients. Furthermore,
      within each group of patients undergoing either the medial or inferior pedicle
      technique, the amount of breast tissue removed did not correlate with
      postoperative sensory outcomes.Computer-assisted quantitative neurosensory
      testing is a highly accurate technique for measuring sensibility. The use of this
      technology demonstrates a 10-fold difference in measurable sensory thresholds in
      normal patients from preexisting data using Semmes-Weinstein monofilaments.
      Advances in measurement methods have allowed the authors to compare postoperative
      sensory outcomes reliably using two popular techniques of reduction mammaplasty.

PMID- 12045552
TI  - Dermal suspension flap in vertical-scar reduction mammaplasty.
AB  - Reduction mammaplasty has the following goals: appropriate reduction of breast
      size, symmetric and youthful breast shape, minimal and inconspicuous scars, and
      stable, long-term results. Although the first two parameters can be obtained by
      various reduction techniques, vertical-scar mammaplasty eliminates the horizontal
      inframammary scar, thereby reducing total scar length. Dermal flaps have been
      described in various types of reduction mammaplasty. The refinement of the
      authors' method is the incorporation of a superiorly pedicled dermal flap for
      better and longer-lasting support in vertical-scar reduction mammaplasty. A total
      of 73 vertical breast reductions in 38 patients were performed with this
      technique from May of 1996 to November of 1999. Vertical-scar reduction
      mammaplasty with a dermal suspension flap combines minimal scars with an internal
      support for long-term stability of the breast shape.

PMID- 12045554
TI  - Complications of vascularized fibula graft for reconstruction of long bones.
AB  - The clinical results and complications of the vascularized fibular graft for the
      reconstruction of various long bone defects were reviewed in 60 cases. Bony
      reconstruction was achieved in 57 of the 60 cases; however, various postoperative
      complications occurred in 54 percent of the cases. One case of arterial
      thrombosis of an anastomosed vessel and nine cases of venous congestion of the
      monitoring flap occurred in the early postoperative periods. The authors managed
      the nine cases of venous congestion of the flap conservatively, and all flaps
      survived. Partial necrosis of the flap was noted in eight of these nine cases,
      but additional surgical intervention was required in only four cases. Treatment
      included a gastrocnemius musculocutaneous flap in one case and a full-thickness
      skin graft in three cases. The vascularized fibula survived and bony fusion was
      achieved in all of these cases. The one case of arterial thrombosis resulted in
      graft failure due to a delay in the decision to perform a thrombectomy. Graft
      fracture occurred in 13 cases as the mechanical stress to the graft increased. In
      two cases of femoral reconstruction, graft fracture occurred during dynamization
      of the graft, despite the use of an Ilizarov external fixator. Correct alignment
      between the recipient bone and the external fixator is a prerequisite to
      preventing graft fracture. Vascularized fibular grafting offers the patient a
      great deal of benefit; however, this graft has a concomitant high risk of
      complications. Great attention to detail must be paid to prevent postoperative
      complications.

PMID- 12045555
TI  - Super sural neurofasciocutaneous flaps in acute traumatic heel reconstructions.
AB  - Conventional reversed sural flaps have been used to cover heel defects; however,
      the experience of the authors indicates that the reach of these flaps falls just
      short of the critical area to be covered. With the limitation being the location
      of the flap (the middle third of the leg), the authors thought that if the flap
      territory were extended proximally, they would have a super flap with immense
      potential. Nevertheless, the critical question remained, "How far?" The massive
      earthquake in January of 2001 in Gujarat, India, made medical personnel pressed
      for time, manpower, resources, and other ancillary supports. The authors were
      forced to make some innovations in their management of extensive heel defects. On
      the basis of preexisting anatomic studies, they developed the possibility of
      using distally based neuroskin flaps of huge dimensions that extend well beyond
      the conventional confines. The versatility of this extended, reversed, neuro
      fasciocutaneous flap in regard to its reliability and safety, despite its huge
      dimensions, is commendable. The hallmarks of this successful extended sural flap,
      which the authors used to cover large heel defects, were basically accurate
      understanding of the anatomy and the use of Doppler to map the perforators and
      the lesser saphenous vein for inclusion in the lie of the pedicle. The authors
      share their experience of five cases of difficult heel reconstructions salvaged
      with this flap, which made them attempt to define maximum flap dimensions that
      can be harvested. The authors learned that the flap can be extended proximally to
      include the entire upper one-third of the leg posteriorly, drastically improving
      its reach and size, without compromising safety. The largest flap used measured
      17 x 16 cm, far more than ever reported in the literature. The flaps truly
      deserve the classification of "super," which is usually reserved for Ponten's
      flaps.

PMID- 12045556
TI  - Free flap reconstruction of the sole of the foot with or without sensory nerve
      coaptation.
AB  - The authors present a retrospective study on major plantar foot reconstruction to
      evaluate the role of the free fasciocutaneous flap and the importance of sensory
      nerve reconstruction in improving long-term results. Between 1995 and 1999, 20
      patients with major defects of the sole of the foot underwent free forearm flap
      reconstruction performed by the senior author (F.S.). Sensory nerve
      reconstruction was added to this technique in 1997. The age and sex of the
      patients and the cause, location, and dimensions of their defects were recorded.
      The patients were clinically and neurophysiologically evaluated at 3, 6, and 12
      months after the procedure for the following parameters: flap contour, flap
      stability, load capacity, walking ability, touch sensation, pain sensation,
      static two-point discrimination, and thermal sensibility. Dermatomic
      somatosensory-evoked potentials were also tested at 12 months. Follow-up ranged
      from 1 to 5 years. Patients were divided into two groups according to sensory
      nerve reconstruction. Group A consisted of 11 patients with nerve repair, and
      group B consisted of nine patients without nerve repair. One patient from group A
      who had an idiopathic neuropathy was excluded from the study because of
      interference with the reinnervation process. Five more patients (three from group
      A and two from group B) were lost at follow-up and excluded from the study. The
      final sample size in each group was seven. Data from both groups were compared
      and statistically analyzed with the Mann-Whitney test and the Fisher exact test.
      Long-term results confirmed in all reconstructions long-lasting stability. During
      the first postoperative year, patients with sensory nerve reconstruction showed
      better sensibility. The statistical analyses confirmed significant differences
      between the two groups to be dependent upon surgical technique at 3 and 6 months.
      Two-point discrimination and dermatomic somatosensory-evoked potentials were
      recorded. After 12 months, flaps without surgical nerve repair showed progressive
      improvement of sensitive thresholds, achieving a good protective sensibility,
      similar to that of the other group, but these flaps never regained two-point
      discrimination or dermatomic somatosensory-evoked potentials.

PMID- 12045558
TI  - The gluteal fasciocutaneous rotation-advancement flap with V-Y closure in the
      management of sacral pressure sores.
AB  - The sacral region is one of the most frequent sites of pressure sore development,
      and local flaps in the gluteal region are usually preferred when surgical closure
      is needed. The authors used the gluteal fasciocutaneous rotation-advancement flap
      with V-Y closure to manage sacral pressure sores in 15 patients. The design was a
      combination of the classic rotation and V-Y advancement flap patterns. When the
      wound was closed, the tension at the distal end of the rotation flap was relieved
      by flap advancement and the combined rotation-advancement action was supported
      laterally with V-Y closure. A wide skin pedicle was preserved at the inferomedial
      part of the flap. This pedicle augmented the blood supply to the flap skin and
      kept the surgical incision small, thus helping to reduce the risk of fecal
      contamination and associated wound-healing problems. This flap can also be
      converted to any design of fasciocutaneous or musculocutaneous V-Y advancement
      flap, should such a change be required. The largest defects that were closed with
      a unilateral rotation-advancement flap and bilateral rotation-advancement flaps
      were 12 and 18 cm in diameter, respectively. In 1.5 to 35 months of follow-up,
      none of the patients developed wound dehiscence or flap necrosis requiring
      repeated surgery. This technique is simple, can be performed quickly, has minimal
      associated morbidity, and yields a good outcome.

PMID- 12045559
TI  - The prepuce free flap in 10 patients: modifications in flap design and surgical
      technique.
AB  - The prepuce free flap was used in 10 oral and oropharyngeal reconstructions.
      During the course of this study, various modifications took place. Residual
      penile skin necrosis and skin island necrosis early in the series led to
      modification of flap design. This solved the donor-site problem by placing the
      skin island more proximally, to consist of the outer layer of the prepuce and an
      equidimensional area of penile skin proximal to the prepuce. Identification of
      the vascular pedicle was greatly facilitated by changing to retrograde
      dissection, making skin incision in the mons veneris superfluous. Incongruence
      between donor and recipient artery, together with microsurgical arrogance,
      resulted in (resolvable) inflow problems in four patients. One flap was lost.
      After modification, marginal necrosis still occurred in one flap, most likely
      because of an episode of venous congestion. Although much care was taken to not
      harvest more skin than in a regular circumcision, penile skin shortage,
      especially during erection, appeared to be the major long-term shortcoming of
      this flap. Flap thinness and pliability, both expected strongholds of the flap,
      were evident during flap inset, but less apparent during follow-up because of
      postoperative radiotherapy in the majority of the cases. The best indications for
      this flap include defects in the tonsillar area extending into the soft palate,
      tongue, lateral oropharynx, retromolar trigonum, gums, and vallecula.

PMID- 12045561
TI  - Craniosynostosis and altered patterns of fetal TGF-beta expression induced by
      intrauterine constraint.
AB  - Recent work has demonstrated that fusion of the calvarial sutures is mediated by
      locally elaborated soluble growth factors, including the transforming growth
      factor-betas (TGF-betas), leading some to speculate that external biomechanical
      forces play little role in suture development. Clinical evidence has long
      suggested, however, that fetal head constraint may play a critical role in the
      pathogenesis of many cases of nonsyndromic craniosynostosis. The purpose of these
      experiments was to test the hypothesis that intrauterine constraint leads to an
      alteration in normal patterns of TGF-beta expression and that these alterations
      are associated with craniosynostosis. Fetal constraint was induced by allowing
      C57Bl/6 murine fetuses to grow for 2.5 days beyond the normal 20-day gestation by
      performing uterine cerclage on the eighteenth day. Cranial suture morphology was
      examined in hematoxylin and eosin-stained sections and in cleared whole-mount
      specimens, double stained with alizarin red S and Alcian blue. Expression
      patterns of TGF-beta1 and TGF-beta3 were examined by immunohistochemical
      techniques. Gross and microscopic examination of the cranial sutures of 17
      constrained fetuses revealed changes that ranged from narrowing to complete
      osseous obliteration of the coronal and squamosal sutures. All sutures of 14
      nonconstrained control pups remained patent. Fetal head constraint was associated
      with increased TGF-beta1 immunoreactivity within the new bone and the underlying
      dura when compared with nonconstrained age-matched controls. TGF-beta3
      immunoreactivity was associated with the dura underlying patent, nonconstrained
      sutures, whereas constraint-induced synostosis was characterized by down
      regulation of dural TGF-beta3 expression. These experiments confirm the ability
      of intrauterine constraint to induce premature fusion of the cranial sutures and
      provide evidence that intrauterine head constraint induces the expression of
      osteogenic growth factors in fetal calvarial bone and the underlying dura.

PMID- 12045563
TI  - The fetal cleft palate: III. Ultrastructural and functional analysis of palatal
      development following in utero repair of the congenital model.
AB  - The role of fetal surgery in the management of congenital anomalies and
      intrauterine abnormalities is appropriately restricted on the basis of
      feasibility and risk-to-benefit analyses of intrauterine intervention. Recently,
      the authors demonstrated that in utero cleft palate repair of the congenital
      caprine model is technically feasible and results in scarless healing of the
      mucoperiosteum and velum, with subsequent development of a potentially functional
      bilaminar palate with distinct oral and nasal mucosal layers, following single
      layer repair of the fetal mucoperiosteal flaps. A slight indentation at the site
      of repair was the only remaining evidence of a cleft. At 6 months of age, normal
      palatal architecture, including that of mucosal, muscular, and glandular
      elements, was seen grossly and histologically. The present work investigated the
      ultrastructural and functional aspects of the palate following in utero cleft
      repair to determine what benefits might be derived from fetal intervention. Six
      goats pregnant with twins were gavaged twice daily for 10 days (gestational days
      32 to 41; term, 145 days) with dry, ground Nicotiana glauca plant delivering
      between 2.4 and 14 mg/kg per day of anabasine, doses that were adjusted in
      response to mater-nal toxicity. At 85 days' gestation, six fetuses underwent in
      utero palatoplasty using a modified von Langenbeck technique with elevation of
      bilateral mucoperiosteal flaps and lateral relaxing incisions. A single-layer
      repair of the mucoperiosteal flaps was performed using interrupted 6-0 Vicryl
      sutures. Six fetuses remained as unrepaired clefted controls. Six months after in
      utero palatoplasty, each group of goats underwent nasoendoscopy to evaluate
      palatal function; two unclefted 6-month-old goats served as controls.
      Subsequently, soft palate muscle was harvested from each of the goats and was
      evaluated by light and electron microscopy. Velar muscle was also harvested from
      the unclefted control goats and was similarly studied. Nasoendoscopy demonstrated
      functional palates capable of dynamic velopharyngeal closure following in utero
      cleft repair; this motion was similar to that observed in unclefted animals.
      Unrepaired clefted goats did not demonstrate any evidence of velar motion or
      velopharyngeal closure. Soft palate muscle from this group demonstrated evidence
      of myofibril degeneration, atrophy, and loss compared with unclefted control
      velar muscle. Ultrastructural changes included sarcomere "scalloping, " partial Z
      line degeneration and loss, and progressive I-band degeneration and loss.
      Repaired clefted soft palate muscle was remarkably similar to unclefted control
      muscle. Significantly less myofibril, Z-line, and I-band degeneration and loss
      were observed with minimal evidence of sarcomere scalloping. In utero cleft
      palate repair results in a functional soft palate with restoration of
      ultrastructural architecture of the velum. These findings were attributed to
      reconstitution of the velar muscular sling, which is disrupted during the
      clefting process and remains abnormally inserted into the posterior edge of the
      palatal bone and along the bony cleft. Although repaired velar muscle does
      demonstrate some evidence of ultrastructural change compared with control muscle,
      these findings are significantly less pronounced than those observed in the
      unrepaired clefted muscle.

PMID- 12045564
TI  - Rescue of an in vitro palate nonfusion model using interposed embryonic
      mesenchyme.
AB  - The authors previously established an in vitro palate nonfusion model on the
      basis of a spatial separation between prefusion embryonic day 13.5 mouse palates
      (term gestation, 19.5 days). They found that an interpalatal separation distance
      of 0.48 mm or greater would consistently result in nonfusion after 4 days in
      organ culture. In the present study, they interposed embryonic palatal
      mesenchymal tissue between embryonic day 13.5 mouse palatal shelves with
      interpalatal separation distances greater than 0.48 mm in an attempt to "rescue"
      this in vitro palate nonfusion phenotype. Because no medial epithelial bilayer
      (i.e., medial epithelial seam) could potentially form, palatal fusion in vitro
      was defined as intershelf mesenchymal continuity with resolution of the medial
      edge epithelia bilaterally. Forty-two (n = 42) palatal shelf pairs from embryonic
      day 13.5 CD-1 mouse embryos were isolated and placed on cell culture inserts at
      precisely graded distances (0, 0.67, and 0.95 mm). Positive controls consisted of
      shelves placed in contact (n = 6). Negative controls consisted of shelves placed
      at interpalatal separation distances of 0.67 mm (n = 6) and 0.95 mm (n = 7) with
      no interposed mesenchyme. Experimental groups consisted of embryonic day 13.5
      palatal shelves separated by 0.67 mm (n = 11) and 0.95 mm (n = 12) with
      interposed lateral palatal mesenchyme isolated at the time of palatal shelf
      harvest. Specimens were cultured for 4 days (n = 19) or 10 days (n = 23),
      harvested, and evaluated histologically. All positive controls at 4 and 10 days
      in culture showed complete histologic palatal fusion. All negative controls at 4
      days and 10 days in culture remained unfused. Five of six palatal shelves
      separated at 0.67 mm interpalatal separation distance with interposed mesenchyme
      were fused at 4 days, and all five were fused at 10 days. At an interpalatal
      separation distance of 0.95 mm with interposed mesenchyme (n = 12), no palates
      (zero of four) were fused at 4 days, but seven of eight were fused at 10 days.
      These data suggest that nonfused palatal shelves can be "rescued" with an
      interposed graft of endogenous embryonic mesenchyme to induce fusion in vitro.

PMID- 12045565
TI  - Effects of mandibular distraction osteogenesis on the inferior alveolar nerve: an
      experimental study in monkeys.
AB  - A series of experimental studies were performed in monkeys to study the effect of
      mandibular distraction osteogenesis on the inferior alveolar nerve at different
      times before and after distraction. A mandible osteotomy was performed and
      distraction was carried out unilaterally in 10 young rhesus monkeys and
      bilaterally in six. The intact nerves on the contralateral side of the 10 monkeys
      were used for the control. Care was taken to avoid destroying the integrity of
      the inferior alveolar nerve during the surgical procedure. After a 5-day latency
      period, the distraction device was activated at a rate of 0.5 mm twice each day
      for 15 days. Sensory nerve action potential testing was applied before and 1 day
      after the operation, at completion of distraction, and at 2, 4, 6, 9, and 12
      weeks of fixation. Necropsy was performed at the completion of distraction and 2,
      4, 6, and 12 weeks of fixation. The mental nerves were taken, sectioned, and
      stained with lead citrate and uranyl acetate, and examined with a transmission
      electron microscope. The inferior alveolar nerves in the distraction gap were
      obtained, and paraffin slides were made and stained with hematoxylin and eosin,
      Luxol fast blue, and Bodian methods. The authors found that immediately after the
      mandible osteotomy, most nerves showed signs of slight acute injury; the latency
      was increased by 5.553 percent, and the amplitude was decreased to 1808 microV.
      This might be caused by the surgical procedure or by compressions produced by
      swelling tissues around the nerves. When distraction was completed, the latency
      was prolonged for an average of 22.18 percent, and the amplitude average had
      attenuated to 28.54 percent (804 microV) of the preoperative value on the
      distracted side. Most nerve fibers exhibited signs of degeneration, such as
      myelin disruption, swelling of cell organs greatly increased in axoplasm, axon
      tearing, and myelin fragments engulfed by macrophages. These were nerve reactions
      to the tensions produced by mandible lengthening. As time elapsed, the nerve's
      action potential recovered gradually because of its repairing ability, the
      latency shortened, amplitude increased, Schwann cells proliferated and formed new
      myelin sheaths, and the tearing axons reconnected. After 12 weeks of
      consolidation, there was still a latency of 12.384 percent prolongation because
      of the prolonged conduction distance, and the average amplitude was restored to
      2786 microV, the approximate preoperative value. The nerve seemed to be repaired
      completely; its myelin thickness, axon diameter, and ultrastructure were all
      similar to those of the control. It was concluded that mandibular distraction
      osteogenesis can produce some degree of harmful effects on the function and
      structure of inferior alveolar nerves, but it is reversible and relatively
      slight. Along with the regeneration of the nerve's myelin and axon, the nerve
      function can gradually rehabilitate to a normal level.

PMID- 12045566
TI  - Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular
      endothelial cells: implications for fracture healing.
AB  - The endothelium is a metabolically active secretory tissue, capable of responding
      to a wide array of environmental stimuli. Hypoxia and vascular endothelial growth
      factor (VEGF) are two components of the putative fracture microenvironment. This
      study investigated the role of hypoxia and VEGF on endothelial cell activation as
      it relates to the bone repair process. It was hypothesized that endothelial cells
      may have an important osteogenic role in fracture healing through the production
      of bone morphogenetic protein-2 (BMP-2), an osteogenic cytokine at the fracture
      site. Therefore, BMP-2 mRNA and protein expression in endothelial cells under
      hypoxia and/or VEGF treatment was studied. The authors observed a 2-fold to 3
      fold up-regulation of BMP-2 mRNA expression in bovine capillary endothelial cells
      and human microvascular endothelial cells stimulated with hypoxia or rhVEGF.
      Furthermore, the combined effects of hypoxia and rhVEGF appeared to be additive
      on BMP-2 mRNA expression in bovine capillary endothelial cells. Actinomycin D and
      cycloheximide studies suggested that the increased mRNA expression was
      transcriptionally regulated. BMP-2 protein expression was up-regulated after 24
      and 48 hours of treatment with either hypoxia or rhVEGF in bovine capillary
      endothelial cells. Surprisingly, the data suggest that endothelial cells may play
      not only an angiogenic role but also an osteogenic role by a direct stimulation
      of the osteoblasts, through the enhanced expression of a potent osteogenic
      factor, BMP-2, at the fracture site.

PMID- 12045567
TI  - Ischemic preconditioning by brief extremity ischemia before flap ischemia in a
      rat model.
AB  - Ischemic preconditioning is a protective endogenous mechanism to reduce
      ischemia/reperfusion injury and is defined as a brief period of ischemia the
      authors term "preclamping." This is followed by tissue reperfusion and is
      believed to increase the ischemic tolerance. The objective of this study was to
      determine whether acute remote ischemic preconditioning, which has been reported
      to be successful for other organs, such as the heart, kidney, intestine, and
      liver, will also result in an enhancement of survival in flaps, and whether
      remote ischemic preconditioning is as effective as preclamping. Forty male Wistar
      rats were divided into four experimental groups. An extended epigastric
      adipocutaneous flap (6 x 10 cm) was raised, based on the left superficial
      epigastric artery and vein. In the control group, a 3-hour flap ischemia was
      induced. In the preclamping group, a brief ischemia of 10 minutes was induced by
      clamping the flap pedicle, followed by 30 minutes of reperfusion. Ischemia of the
      right hind limb was induced in the femoral ischemia group by clamping the femoral
      artery and vein for 10 minutes after flap elevation. The limb was then reperfused
      for 30 minutes. Thereafter, flap ischemia was induced as in the control group. A
      similar protocol was used in the tourniquet group. A tourniquet was used to
      induce hind-limb ischemia. The experiment was then performed as in the femoral
      ischemia group. Mean flap necrosis area was assessed for all groups on the fifth
      postoperative day using planimetry software. Average flap necrosis area was 68.2
      +/- 18.1 percent in the control group, 11 +/- 8.38 percent in the preclamping
      group, 12.5 +/- 5.83 percent in the femoral ischemia group, and 24 +/- 11.75
      percent in the tourniquet group. All preconditioned animals demonstrated a
      significantly lower area of flap necrosis than the control group (p < 0.001, one
      way analysis of variance, post hoc Tukey's test). The data show that ischemic
      preconditioning and enhancement of flap survival can be achieved not only by
      preclamping of the flap pedicle but also by induction of an ischemia/reperfusion
      event in a body area distant from the flap before harvest. These findings
      indicate that remote ischemic preconditioning is a systemic phenomenon, leading
      to an enhancement of flap survival. The exact mechanism is not yet completely
      understood. The data suggest that remote ischemic preconditioning could be
      performed simultaneously with flap harvest in the clinical setting, resulting in
      an improved flap survival without prolongation of the operation. This may
      decrease the rate of partial flap loss or fat necrosis, especially in high-risk
      groups such as smokers, those with irradiated tissues, and obese patients.

PMID- 12045568
TI  - The effects of rapamycin in murine peripheral nerve isografts and allografts.
AB  - The FKBP-12-binding ligand FK506 has been successfully used to stimulate nerve
      regeneration and prevent the rejection of peripheral nerve allografts. The
      immunosuppressant rapamycin, another FKBP-12-binding ligand, stimulates axonal
      regeneration in vitro, but its influence on nerve regeneration in peripheral
      nerve isografts or allografts has not been studied. Sixty female inbred BALB/cJ
      mice were randomized into six tibial nerve transplant groups, including three
      isograft and three allograft (C57BL/6J) groups. Grafts were left untreated
      (groups I and II), treated with FK506 (groups III and IV), or treated with
      rapamycin (groups V and VI). Nerve regeneration was quantified in terms of
      histomorphometry and functional recovery, and immunosuppression was confirmed
      with mixed lymphocyte reactivity assays. Animals treated with FK506 and rapamycin
      were immunosuppressed and demonstrated significantly less immune cell
      proliferation relative to untreated recipient animals. Although every animal
      demonstrated some functional recovery during the study, animals receiving an
      untreated peripheral nerve allograft were slowest to recover. Isografts treated
      with FK506 but not rapamycin demonstrated significantly increased nerve
      regeneration. Nerve allografts in animals treated with FK506, and to a lesser
      extent rapamycin, however, both demonstrated significantly more nerve
      regeneration and increased nerve fiber widths relative to untreated controls. The
      authors suggest that rapamycin can facilitate regeneration through peripheral
      nerve allografts, but it is not a neuroregenerative agent in this in vivo model.
      Nerve regeneration in FK506-treated peripheral nerve isografts and allografts was
      superior to that found in rapamycin-treated animals. Rapamycin may have a role in
      the treatment of peripheral nerve allografts when used in combination with other
      medications, or in the setting of renal failure that often precludes the use of
      calcineurin inhibitors such as FK506.

PMID- 12045569
TI  - Treatment options in extravasation injury: an experimental study in rats.
AB  - Local skin necrosis after extravasation of doxorubicin hydrochloride
      (Adriamycin), a widely used chemotherapeutic agent, is a common problem in cancer
      patients. Even though several treatment options have been proposed for
      extravasation injury, there is still controversy regarding the management of such
      lesions. The aim of this study was to compare the efficacy of saline
      infiltration, vitamin C infiltration, suction technique, and early surgical
      excision as a treatment in a rat extravasation model. The authors planned their
      study in two stages. In stage 1, the lowest effective dose of doxorubicin at
      which a homogeneous skin necrosis was formed and the method of administration
      were investigated. Intradermal and subpannicular injections were made for six
      rats, using six different concentrations of doxorubicin (0.33, 0.5, 0.66, 1.0,
      1.33, and 1.5 mg/ml). In stage 1, the intradermal injection produced homogeneous
      and uniform tissue necrosis. In stage 2, the efficacy of saline infiltration
      (group 1), vitamin C infiltration (group 2), suction (group 3), suction and
      saline washout (group 4), suction and vitamin C washout (group 5), and early
      surgical excision (group 6) was compared. The treatment options were applied 2
      hours after doxorubicin injection. At the end of the seventh day, the presence
      and size of ulcers at the injection site were calculated. Fourteen days after
      injection, a histopathologic examination was performed for each treatment and
      control group. In groups 1 and 3, there was no statistically significant
      difference in the size of necrosis compared with the control groups. In groups 2,
      4, and 5, the size of necrosis was smaller compared with the control groups, and
      this was statistically significant. Furthermore, in group 4 (suction and saline
      washout) and group 5 (suction and vitamin C washout), the calculated area of
      necrosis was smaller compared with other treatment groups, and this was
      statistically significant. The findings supported the assertion that suction and
      saline or vitamin C washout reduce necrotic tissue size in extravasation injury.

PMID- 12045570
TI  - Metachronous flaps from the same subscapular axis.

PMID- 12045571
TI  - A pedicle forearm fillet flap aided by subperiosteal proximal dissection in
      shoulder disarticulation.

PMID- 12045572
TI  - Distraction osteogenesis after toe-to-thumb transplantation.

PMID- 12045573
TI  - Use of an innervated tongue flap to rehabilitate the tongue after hypoglossal-to
      facial nerve transfer.

PMID- 12045574
TI  - New prospects in the treatment of traumatic and postoperative parotid fistulas
      with type A botulinum toxin.

PMID- 12045575
TI  - A subcostal artery perforator flap for a lumbar defect.

PMID- 12045577
TI  - The hidden art in plastic surgery...in five stages of creativity.

PMID- 12045576
TI  - Stretch and growth: the molecular and physiologic influences of tissue expansion.

PMID- 12045578
TI  - Carpal tunnel release through a limited skin incision under direct visualization
      using a new instrument, the carposcope.

PMID- 12045579
TI  - Auricular reconstruction for microtia: part I. Anatomy, embryology, and clinical
      evaluation.

PMID- 12045580
TI  - Plastic surgery: staying inside the lines.

PMID- 12045581
TI  - The prevention of emesis in plastic surgery: a randomized, prospective study.
AB  - Perhaps the most unpleasant experience following outpatient plastic surgery
      procedures is postoperative nausea and vomiting. Postoperative nausea and
      vomiting often results in delayed recovery time and unintended admission, and it
      can be a contributing factor to the formation of hematoma following rhytidectomy.
      Ondansetron (Zofran) has proven benefit in preventing postoperative nausea and
      vomiting if given before general anesthesia in a variety of surgical procedures.
      Its utility in cases performed under conscious sedation has not been determined.
      The purpose of this study was (1) to test the ability of prophylactic ondansetron
      to prevent postoperative nausea and vomiting in plastic surgery cases performed
      under conscious sedation, and (2) to determine relative risk factors for
      postoperative nausea and vomiting and a selection policy for the administration
      of antiemetic prophylaxis. This was a prospective, randomized, double-blind
      study. One hundred twenty patients were enrolled after giving informed consent.
      Patients received a single dose of either placebo or ondansetron (4 mg
      intravenously) before administration of sedation. Sedation administration
      followed a standardized institutional protocol, using midazolam and fentanyl.
      Data were recorded from a series of three questionnaires: preoperatively,
      immediately postoperatively, and at the time of the first office return. Data
      were confirmed by means of telephone interview, chart analysis, and nursing
      documentation. Multivariate analysis was conducted. Nausea and emesis occurred
      with an overall frequency of 33 percent and 22 percent, respectively.
      Postoperative nausea and vomiting was associated with statistically longer
      recovery periods. The incidence of emesis was statistically higher among women,
      among those undergoing facial rejuvenation, and among those with a history of
      opioid-induced emesis or postoperative nausea and vomiting following a previous
      operation (p < 0.05). The incidence of postoperative nausea and vomiting
      paralleled increases in case duration; the incidence of emesis was zero in cases
      less than 90 minutes in duration. Ondansetron significantly reduced the incidence
      of emesis overall (placebo, 30 percent; ondansetron, 13 percent; p < 0.05).
      Postoperative perception of nausea was significantly lower among those who had
      received ondansetron (p < 0.05). These results confirm the efficacy of
      ondansetron for the prevention of postoperative nausea and vomiting in plastic
      surgery cases under conscious sedation. In those who are at increased risk,
      prophylaxis should be considered. Such risks include female gender, facial
      rejuvenation procedures, and a patient history of opioid-induced emesis or
      postoperative nausea and vomiting following a prior operation. The zero incidence
      of emesis in cases less than 90 minutes does not support the routine use of
      prophylaxis in such cases. Patient satisfaction in plastic surgery is derived
      from the overall subjective experience of the event as much as by the final
      result. By remaining attentive to patient concerns and optimizing perioperative
      care, we can improve the subjective experience for our patients.

PMID- 12045582
TI  - The alar contour graft: correction and prevention of alar rim deformities in
      rhinoplasty.
AB  - One of the most common problems affecting both the primary and secondary
      rhinoplasty patient is deformity of the alar rim. Typically, this deformity is
      caused by congenital malpositioning, hypoplasia, or surgical weakening of the
      lateral crura, with the potential for both functional and aesthetic
      ramifications. Successful correction and prevention of alar rim deformities
      requires precise preoperative diagnosis and planning. Multiple techniques of
      varying complexity have been described to treat this common and challenging
      problem. Over the past 6 years (1994 through 2000), the authors have employed a
      simple technique in 123 patients for alar retraction that involves the
      nonanatomic insertion of an autogenous cartilage buttress into an alar-vestibular
      pocket. Among the 53 patients who underwent primary rhinoplasty in this study, 91
      percent experienced correction or prevention of alar notching or collapse.
      However, correction was achieved for only 73 percent of the patients who
      underwent secondary rhinoplasty; many of whom had alar retraction secondary to
      scarring or lining loss. In patients with moderate or significant lining loss or
      scarring, a lateral crural strut graft is recommended. The alar contour graft
      provides the foundation in the patient undergoing primary or secondary
      rhinoplasty for the reestablishment of a normally functioning external nasal
      valve and an aesthetically pleasing alar contour. This article discusses the
      anatomic and aesthetic considerations of alar rim deformities and the indications
      and the surgical technique for the alar contour graft.

PMID- 12045584
TI  - Anatomical structure of the buccal fat pad and its clinical adaptations.
AB  - Before performing plastic and aesthetic surgery around the buccal area, the
      authors reviewed the anatomical structures of the buccal fat pad in 11 head
      specimens (i.e., 22 sides of the face). The enveloping, fixed tissues and the
      source of the nutritional vessels to the buccal fat pad and its relationship with
      surrounding structures were observed in detail, with the dissection procedure
      described step by step. The dissection showed that the buccal fat pad can be
      divided into three lobes-anterior, intermediate, and posterior-according to the
      structure of the lobar envelopes, the formation of the ligaments, and the source
      of the nutritional vessels. The buccal, pterygoid, pterygopalatine, and temporal
      extensions (superficial and profound) are derived from the posterior lobe. The
      buccal fat pad is fixed by six ligaments to the maxilla, posterior zygoma, and
      inner and outer rim of the infraorbital fissure, temporalis tendon, or buccinator
      membrane. Several nutritional vessels exist in each lobe and in the subcapsular
      vascular plexus forms. The buccal fat pads function to fill the deep tissue
      spaces, to act as gliding pads when masticatory and mimetic muscles contract, and
      to cushion important structures from the extrusion of muscle contraction or outer
      force impulsion. The volume of the buccal fat pad may change throughout a
      person's life. Based on the findings of the dissections, the authors provide
      several clinical applications for the buccal fat pad, such as the mechanism of
      deepening the nasolabial fold and possible rhytidectomy to suspend the anterior
      lobe upward and backward. They suggest that relaxation, poor development of the
      ligaments, or rupture of the buccal fat pad capsules can make the buccal
      extension drop or prolapse to the mouth or subcutaneous layer. As such, the
      authors refined their methods and heightened their focus when using the buccal
      fat pad to perform a random or pedicled buccal fat pad fat flap or to correct a
      buccal skin protrusion or hollow.

PMID- 12045586
TI  - Brow suspension, a minimally invasive technique in facial rejuvenation.
AB  - People tend to prefer noninvasive or minimally invasive methods of facial
      rejuvenation, especially when it involves their face, which is the hallmark of a
      person's identity and impossible to hide. It is widely known that brow ptosis
      gives the face a "tired look" and also accentuates deformities of the upper
      eyelid. Most people who are interested in facial rejuvenation may not accept even
      a minor surgery, such as an endoscopic surgery. The senior author has developed a
      minimally invasive method of suspending the brow at a higher position. In this
      technique, there is neither surgical dissection nor a surgical incision except
      for four stab incisions and suture insertion, which is why we refer to it as a
      nonsurgical brow suspension. It is done under local anesthesia, and the brows are
      fixed in the position that they assume when the patient is supine. In the past 6
      years, we performed 387 brow suspensions on 324 female and 63 male patients. The
      youngest patient was 19 years old, and the oldest was 74 years old. A
      retrospective chart review was done. These 387 cases were reviewed by comparison
      of preoperative and postoperative photographs. This approach was not only used
      for patients who were not interested in surgical rejuvenation but was also
      combined with lipofilling, laser resurfacing, and/or upper blepharoplasty. This
      technique is useful for correcting postsurgical brow asymmetry. We present this
      technique as an adjunct to the established techniques of facial rejuvenation.
      Despite the high patient acceptance and technical ease, it is not a replacement
      for the established techniques of facial rejuvenation.

PMID- 12045588
TI  - Geometric incision designing for abdominoplasty.

PMID- 12045590
TI  - Face lifts with hidden scars: the vertical U incision.
AB  - The authors present their latest development of a strictly vertical
      retroauricular incision to minimize a sequela of a face lift, namely, a visible
      scar. The temporal preauricular vertical incision and the retroauricular vertical
      incision form two parallel arms of a U-shaped incision. Anteriorly, a downward
      rotation flap is made to maintain the horizontal temporal line at the right
      level, and posteriorly, the scalp is incised vertically, followed by extensive
      superficial retroauricular undermining. In both temporal and retroauricular
      areas, skin and scalp undergo a redistribution rather than resection, which is
      extremely limited. The authors' experience with 100 patients who were operated on
      with vertical U incisions since April of 2000 is described. A total of 35
      patients were evaluated after a 6-month follow-up by using clinical and
      photographic examinations. There were very few complications because the
      extensive retroauricular flap has good viability. There were no problems with
      sensitivity, hair loss, or scar spreading, and the hairline was not displaced.
      The quality of the scar was excellent in the majority of cases. We experienced
      only a few hypertrophic but well-hidden scars. This approach can also be used in
      secondary cases when the primary scar is of good quality. The neck pull is as
      effective as that in the classic approach with a traverse retroauricular
      incision. The nondetectability of the retroauricular scar is of special interest
      in young patients and in men. The authors believe there is no contraindication
      for this technique. It does not significantly prolong the operating time. It
      includes a large undermining in the retroauricular area (6 cm from the sulcus),
      but this dissection is easily performed in the superficial plane. In addition to
      using fibrin glue in the undermined areas, the authors drain the neck. They do
      not use dressings. Recovery was fast, and there were only two instances of
      hematomas and two instances of subcutaneous cervical fluid collections in which
      patients required treatment.

PMID- 12045592
TI  - Breast deformity caused by anatomical or teardrop implant rotation.

PMID- 12045594
TI  - The role of preoperative antibiotic prophylaxis in cosmetic surgery.
AB  - An estimated 2.7 million cosmetic procedures were performed in the United States
      in 1998, yet the role of preoperative antibiotic prophylaxis for cosmetic surgery
      is not clearly defined. Routine antibiotic prophylaxis for cosmetic procedures
      was discontinued by the senior author at the authors' institution in an effort to
      reduce use and cost in June of 1999. Subsequently, a cluster of four
      Staphylococcus aureus postoperative surgical site infections were identified. A
      case-control study to identify risk factors for surgical site infections in these
      patients was performed. All patients who underwent cosmetic surgical procedures
      by the senior author during June of 1999 and did not develop a surgical site
      infection were selected as control patients. Four case patients and 12 control
      patients were included in the study. The significant risk factors associated with
      surgical site infections were the mean duration of procedure (5 hours versus 2
      hours; p = 0.02), general anesthesia (p = 0.004), and placement of a Blake drain
      (p = 0.004). No common source of infection was identified by review and
      observation of surgical technique. Pulse-field gel analysis of the S. aureus
      isolates from the four case patients and the nares of surgical personnel revealed
      no common strain. After the reinstitution of preoperative antibiotic prophylaxis
      with cefazolin for procedures anticipated to last 3 hours or longer, no
      additional surgical site infections were identified through December of 1999
      (four of 29 versus none of 104; p = 0.002). It was concluded that targeted
      antibiotic prophylaxis for cosmetic surgery with cefazolin may be useful in
      reducing surgical site infections attributable to S. aureus.

PMID- 12045596
TI  - Why the transumbilical breast augmentation is safe for implants.

PMID- 12045597
TI  - In the vastness of time and the universe...

PMID- 12045598
TI  - The current status of tissue glues: I. For bone fixation.

PMID- 12045601
TI  - Neurofibromatosis associated with phthisis bulbi.

PMID- 12045602
TI  - Results with Furlow palatoplasty in the management of velopharyngeal
      insufficiency.

PMID- 12045603
TI  - Perceptual and instrumental assessment of velopharyngeal insufficiency.

PMID- 12045604
TI  - More on vascular malformations.

PMID- 12045605
TI  - The combined use of classic and reverse abdominoplasty on the same patient.

PMID- 12045606
TI  - Intraarticular injections of sodium hyaluronate for temporomandibular joint
      disorder.

PMID- 12045607
TI  - Entrapment neuropathy of the upper extremity in hemodialysis patients.

PMID- 12045608
TI  - Orthognathic surgery for trichorhinophalangeal syndrome type I.

PMID- 12045609
TI  - Prevention of stiff upper lip complication of lip enhancement.

PMID- 12045610
TI  - The four-point setback: a simple, objective method to satisfy patients in
      prominent ear surgery.

PMID- 12045611
TI  - EMTALA laws and the plastic surgeon in the emergency department.

PMID- 12045612
TI  - Technical refinement in breast reduction using the inferior pedicle technique.

PMID- 12045613
TI  - Crutch glasses for blepharoptosis.

PMID- 12045614
TI  - Minimizing donor-site morbidity from thoracic flaps for coverage of the upper
      limbs in women.

PMID- 12045615
TI  - Establishing the site of the A-1 pulley.

PMID- 12045616
TI  - The Buruli type ulcer.

PMID- 12045617
TI  - Successful treatment of chronic wound in Klippel-Trenaunay syndrome with
      recombinant human platelet-derived growth factor-BB.

PMID- 12045618
TI  - New treatment of steroid-induced fat atrophy.

PMID- 12045619
TI  - A new classification of palatal fracture and an algorithm to establish a
      treatment plan.

PMID- 12045620
TI  - Periareolar subpectoral breast augmentation.

PMID- 12045621
TI  - Alar nose graft.

PMID- 12045622
TI  - Use of the SpaceMaker balloon in sternal wound closure: comparison with other
      techniques.

PMID- 12045623
TI  - Unusual complication after genioplasty.

PMID- 12045624
TI  - Y-V advancement flaps for labial adhesions in postmenopausal women.

PMID- 12045625
TI  - Scientific data from clinical trials: investigators responsibilities and rights.

PMID- 12045626
TI  - Survival of seriously injured patients first treated in rural hospitals.
AB  - BACKGROUND: Patients injured in rural counties are hypothesized to have improved
      survival if local hospitals are categorized as Level III, Level IV, and Level V
      trauma centers. METHODS: Data were abstracted on patients with brain, liver, or
      spleen injuries who were first treated in 16 rural hospitals in Oregon (with
      categorized trauma centers) and 16 hospitals in Washington (without categorized
      trauma centers). Logistic regression models evaluated survival up to 30 days
      after hospital discharge. RESULTS: Among Oregon's 642 study patients, 63% were
      transferred to another hospital. Among Washington's 624 patients, a higher
      proportion, 70%, were transferred. Risk-adjusted odds of death for Washington
      patients (reference odds, 1) were the same as for Oregon patients (odds ratio,
      0.82; 95% confidence interval, 0.53-1.28). Most patients died after transfer to
      another hospital. CONCLUSION: In states with a prevailing practice of promptly
      transferring brain-injured patients, survival of these patients may not be
      enhanced by categorization of hospitals as rural trauma centers. To further
      improve the outcome of these patients, policy makers should adjust statewide
      trauma system guidelines to enhance integration and to perfect coordination among
      sequential decision makers.

PMID- 12045627
TI  - Could a regional trauma system in eastern Switzerland decrease the mortality of
      blunt polytrauma patients? A prospective cohort study.
AB  - BACKGROUND: In Europe and Switzerland, hardly any studies have been performed on
      regional trauma systems. We therefore decided to conduct a prospective study in
      our region to establish whether an organized trauma system derived from the
      American model would have a beneficial effect on the survival of blunt polytrauma
      patients. METHODS: In a prospective observational cohort study conducted between
      1990 and 1996, we compared the actual mortality in 280 blunt polytrauma patients
      admitted directly to our trauma center with the predicted mortality using the A
      Severity Characterization of Trauma score. The same comparison was made for 190
      transferred polytrauma admissions from regional hospitals. Our hypothesis was
      that for the transferred admissions, the actual mortality would be significantly
      higher than predicted, but that there would be no difference for the directly
      admitted patients. Inclusion criteria were blunt trauma of at least two body
      sites and an Injury Severity Score of 8 or more. RESULTS: Mortality in the
      patients admitted directly to the trauma center was 11.8% (33 of 280), which was
      not significantly lower than that for the transferred admissions at 14.2% (27 of
      190). There were 10% (3 of 30) more deaths than predicted among the direct
      admissions (i.e., 3 more deaths; 95% confidence interval, -5.2-11.1; p = NS).
      Among the transferred admissions, there were 46% (8.6 of 18.4) more deaths than
      predicted (i.e., 8.6 more deaths; 95% confidence interval, 2.5-14.7; p < 0.05).
      CONCLUSION: It is likely that a regional trauma system in eastern Switzerland for
      polytrauma patients with an ISS of 8 or more would have a moderately positive
      effect on mortality. During the period of observation, transferred admissions
      from regional hospitals to our trauma center had a 46% higher mortality than
      predicted. In absolute terms, therefore, with a regional trauma system, it might
      have been possible to avoid between one death every 2 to 3 years and two to three
      deaths every year.

PMID- 12045628
TI  - A protocolized approach to pulmonary failure and the role of intermittent prone
      positioning.
AB  - INTRODUCTION: We present a series of adult patients treated under a protocol for
      severe lung failure (acute respiratory distress syndrome [ARDS]) that uses
      positive end-expiratory pressure (PEEP) optimization and intermittent prone
      positioning (IPP) to reduce shunt, improve oxygen (O(2)) delivery, and reduce
      FiO(2). METHODS: Trauma, emergency vascular, and general surgical patients with
      PaO(2)/FiO)(2) (PF) ratio < 200 were entered into a protocol designed to maintain
      mixed venous saturation (SVO(2)) > 70% with FiO(2) < 0.50. Therapy involved a
      sequential algorithmic approach that included pulmonary artery oximetry, "best
      PEEP" determination, optimization of cardiac function, limitation of VO(2),
      transfusion to hematocrit of 35%, frequent bronchoscopy, rational diuresis and,
      if the FiO(2) was > 0.50, a trial of IPP with every-6-hour rotations. Unstable
      spine fractures and pelvic external fixators were the only contraindications to
      IPP. We collected data prospectively and from the charts and trauma registry.
      RESULTS: Forty adults were treated by protocol, 29 were injured and 11 had
      vascular or general surgical primary problems. The patients were 46.3 +/- 3.1
      years old (the trauma patients were 42.9 +/- 3.2, and the vascular/general
      patients were 62 +/- 7.5 years old). Average Injury Severity Score was 25.9 +/-
      3.7 and the Murray lung injury score was 2.65 +/- 0.9. IPP was used in all
      patients including those with recent tracheostomy, open abdomens, laparotomy,
      thoracotomy, leg external fixators, central nervous system injury, continuous
      venovenous hemofiltration and extracorporeal membrane oxygenation cannulae,
      vasopressor therapy, recent chest wall open reduction and internal fixation, and
      facial fractures. With the initiation of IPP therapy, the PF ratio increased from
      132.1 +/- 8.5 to 231.6 +/- 14.2 (p < 0.001), the FiO(2) was decreased from 65.9
      +/- 4.0% to 47.0 +/- 1.1% (p < 0.001), and the SVO(2) increased from 75.3 +/-
      1.8% to 78.6 +/- 1.6% (p = 0.023). PEEP and static compliance were unchanged. The
      duration of IPP was 85.6 +/- 14.9 hours (median, 55 hours; range, 12 to 490
      hours). Within 48 hours, all patients were on FiO(2) < or = 50. Mortality was 20%
      (14% for trauma) and none died of ARDS. The only complications of IPP were one
      case of partial-thickness skin loss from a malpositioned nasogastric tube and a
      case of transient lingual edema. CONCLUSION: IPP was independently responsible
      for an increase in PF ratio and SVO(2). We effectively and safely used IPP in our
      patients with ARDS, including many with issues generally considered to be
      contraindications. IPP and best-PEEP therapy enabled us to wean all of our
      patients' Fio2 to < or = 0.50 within 48 hours of ARDS onset.

PMID- 12045629
TI  - Shock mesenteric lymph-induced rat polymorphonuclear neutrophil activation and
      endothelial cell injury is mediated by aqueous factors.
AB  - BACKGROUND: After trauma and hemorrhagic shock (T/HS), mesenteric lymph (ML)
      activates polymorphonuclear neutrophils (PMNs), injures endothelial cells (ECs),
      and predisposes to lung injury. The involved mediators, however, are unknown. We
      studied the ability of aqueous (AQ) and lipid (LIP) extracts of rat T/HS ML to
      activate PMNs and injure ECs. METHODS: ML was collected from male rats undergoing
      trauma (laparotomy) plus hemorrhagic shock (30 mm Hg, 90 minutes) or sham shock.
      AQ and LIP ML fractions were separated using the Bligh-Dyer technique. Human
      umbilical vein endothelial cells were incubated 18 hours in 5% LIP or AQ lymph
      fractions and viability was assessed using the MTT assay. Rat PMNs incubated 5
      minutes with 3% LIP or AQ fractions were assessed for respiratory burst (RB) and
      cytosolic calcium ([Ca(2+)](i)) using dihydrorhodamine 123 and fura-2AM. Human
      PMN responses to AQ and LIP T/HS lymph were studied similarly. RESULTS: EC
      incubated in AQ showed 19 +/- 4% viability as compared with 65 +/- 11% in LIP (p
      < 0.001). Whole lymph affected ECs comparably to AQ T/HS lymph. Rat PMN basal
      [Ca(2+)](i) increased after exposure to AQ but not LIP T/HS lymph extracts. AQ
      T/HS lymph primed [Ca(2+)](i) responses to macrophage inflammatory protein-2 and
      platelet-activating factor; neither LIP T/HS nor any trauma and sham shock lymph
      fraction caused PMN priming. Rat PMN RB was elevated after AQ T/HS lymph
      incubation when compared with buffer (610 +/- 122 U/s vs. 225 +/- 38 U/s, p =
      0.01). Rat PMN incubation in LIP T/HS lymph caused minimal activation (289 +/- 28
      U/s, p = NS). Conversely, human PMN showed [Ca(2+)](i) and RB priming by rat T/HS
      LIP and not AQ extracts. CONCLUSION: T/HS mesenteric lymph contains multiple
      biologically active mediators. Both AQ and LIP extracts of T/HS lymph are toxic
      to human umbilical vein endothelial cells, with AQ more active than LIP. Only AQ
      T/HS lymph activates rat PMNs, although LIP rat lymph extract activates human
      PMNs. These findings demonstrate the complex nature of gut lymph-derived biologic
      factors as well as species-specific differences on PMN and EC physiology.
      Therapies directed at any one specific molecule or mediator are therefore
      unlikely to be successful.

PMID- 12045630
TI  - Rapid body cooling by cold fluid infusion prolongs survival time during
      uncontrolled hemorrhagic shock in pigs.
AB  - OBJECTIVE: The purpose of this study was to examine whether cold fluid infusion
      could rapidly decrease the core temperature and prolong survival during
      uncontrolled hemorrhagic shock in pigs. METHODS: Fourteen pigs under light
      halothane anesthesia and spontaneous breathing underwent initial blood withdrawal
      of 25 mL/kg over 15 minutes, followed by uncontrolled hemorrhage (5-mm
      aortotomy). Immediately after the aortotomy, the pigs were randomized to receive
      500 mL lactated Ringer's solution at either 4 degrees C (group 1, n = 7) or 37
      degrees C (group 2, n = 7) over 20 minutes through the internal jugular vein and
      observed until their death or for a maximum of 240 minutes. RESULTS: The
      pulmonary artery temperature of group 1 decreased to 35.5 degrees +/- 0.3 degrees
      C after the infusion, then remained at 35.5 degrees C during the observation
      period. Pulmonary artery temperature values of group 2 remained at around 37.5
      degrees C throughout the experiment. The mean survival time was 220 +/- 45
      minutes in group 1 versus 136 +/- 64 minutes in group 2 (p < 0.05, life table
      analysis). The additional intraperitoneal blood loss of group 1 was similar to
      that of group 2 (9 +/- 4 g/kg vs. 10 +/- 5 g/kg). CONCLUSION: In lightly
      anesthetized pigs during uncontrolled hemorrhagic shock, infusion with 4 degrees
      C lactated Ringer's solution (which seems to be feasible in the clinical setting)
      decreases the core temperature rapidly and prolongs survival.

PMID- 12045631
TI  - Dalteparin sodium treatment during resuscitation inhibits hemorrhagic shock
      induced leukocyte rolling and adhesion in the mesenteric microcirculation.
AB  - BACKGROUND: Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte
      (PMN) adhesion and extravasation are pivotal for the development of postinjury
      multiple organ failure. We hypothesized that the deleterious microcirculatory
      consequences of hemorrhagic shock (HS) could be altered by low-molecular-weight
      heparin (LMWH) therapy. Our aim was to investigate the effects of dalteparin
      sodium on leukocyte-endothelial cell interactions when LMWH treatment was
      initiated before HS or during resuscitation. METHODS: Anesthetized dogs underwent
      HS (40 mm Hg mean arterial pressure for 60 minutes) and resuscitation either with
      shed blood or with lactated Ringer's (LR) solution. LMWH or conventional heparin
      sodium pretreatment was administered subcutaneously before hemorrhage; or LMWH
      was given intravenously during resuscitation. Mesenteric postcapillary venules
      were observed by intravital video microscopy before and after HS, and 60 minutes,
      120 minutes, and 180 minutes after resuscitation, and leukocyte rolling and firm
      adherence were determined. RESULTS: HS significantly increased PMN rolling and
      adhesion in the mesenteric microcirculation. LMWH, but not heparin sodium
      pretreatment, significantly inhibited both primary and secondary interactions.
      LMWH treatment was also effective when initiated during resuscitation. LMWH
      exerted the same inhibitory effect regardless of the type of resuscitation.
      CONCLUSION: LMWH treatment during resuscitation effectively inhibits PMN rolling
      and adhesion.

PMID- 12045632
TI  - Injury induces increased monocyte expression of tissue factor: factors associated
      with head injury attenuate the injury-related monocyte expression of tissue
      factor.
AB  - BACKGROUND: Activated monocytes are able to express tissue factor (TF), a potent
      procoagulant. The effect of injury on monocyte TF expression is not known. We
      have found that patients with head injury (HI) have increased antithrombin
      activity and decreased platelet function compared with non-head-injured trauma
      patients. Our objective was to determine whether injury increases TF expression
      by monocytes and whether this increased TF expression is attenuated in patients
      with HI. METHODS: We prospectively enrolled 37 trauma patients (meeting the entry
      criterion of an Injury Severity Score [ISS] > or = 9) and 11 healthy control
      subjects. We sampled blood on arrival and then at 24, 48, and 72 hours. We
      performed flow cytometry with antibody markers for monocytes (CD14), platelets
      (CD42a), and TF. We compared results of patients with HI (Glasgow Coma Scale
      score < or = 9 and Abbreviated Injury Scale Head/Neck score > or = 3) with
      patients without HI and with controls. RESULTS: Patients had a mean ISS of 23.9
      +/- 2.3 (+/- SEM), mean age of 45 +/- 3 years, and mean length of stay of 17.9 +/
      3.2 days. Seventy-six percent were men, and 97% had blunt trauma. The overall
      mortality rate was 11%. Trauma patients had greater monocyte TF expression than
      controls for all time periods (p < 0.05). Trauma patients with HI had elevated
      monocyte TF expression compared with controls for the initial and 24-hour time
      periods, but they subsequently had more rapid return of monocyte TF expression to
      baseline (despite a higher ISS) than trauma patients without HI. Trauma patients
      both with and without HI had increased platelet-monocyte binding at each time
      versus controls. CONCLUSION: Trauma induces TF expression on monocytes. Patients
      with HI have attenuation of this expression by 24 hours after injury. The
      attenuation of TF expression by monocytes in HI parallels the increase in AT and
      the decrease in platelet function seen after HI. The correlation of TF expression
      with platelet-monocyte binding suggests that platelet binding may lead to
      monocyte activation.

PMID- 12045633
TI  - Evaluation of trauma team performance using an advanced human patient simulator
      for resuscitation training.
AB  - BACKGROUND: Human patient simulation (HPS) has been used since 1969 for teaching
      purposes. Only recently has technology advanced to allow application to the
      complex field of trauma resuscitation. The purpose of our study was to validate
      an advanced HPS as an evaluation tool of trauma team resuscitation skills.
      METHODS: The pilot study evaluated 10 three-person military resuscitation teams
      from community hospitals that participated in a 28-day rotation at a civilian
      trauma center. Each team consisted of physicians, nurses, and medics. Using the
      HPS, teams were evaluated on arrival and again on completion of the rotation. In
      addition, the 10 trauma teams were compared with 5 expert teams composed of
      experienced trauma surgeons and nurses. Two standardized trauma scenarios were
      used, representing a severely injured patient with multiple injuries and with an
      Injury Severity Score of 41 (probability of survival, 50%). Performance was
      measured using a unique human performance assessment tool that included five
      scored and eight timed tasks generally accepted as critical to the initial
      assessment and treatment of a trauma patient. Scored tasks included airway,
      breathing, circulation, and disability assessments as well as overall
      organizational skills and a total score. The nonparametric Wilcoxon test was used
      to compare the military teams' scores for scenarios 1 and 2, and the comparison
      of the military teams' final scores with the expert teams. A value of p < 0.05
      was considered significant. RESULTS: The 10 military teams demonstrated
      significant improvement in four of the five scored (p < or = 0.05) and six of the
      eight timed (p < or = 0.05) tasks during the final scenario. This improvement
      reflects the teams' cumulative didactic and clinical experience during the 28-day
      trauma refresher course as well as some degree of simulator familiarization.
      Improved final scores reflected efficient and coordinated team efforts. The
      military teams' initial scores were worse than the expert group in all
      categories, but their final scores were only lower than the expert groups in 2 of
      13 measurements (p < or = 0.05). CONCLUSION: No studies have validated the use of
      the HPS as an effective teaching or evaluation tool in the complex field of
      trauma resuscitation. These pilot data demonstrate the ability to evaluate trauma
      team performance in a reproducible fashion. In addition, we were able to document
      a significant improvement in team performance after a 28-day trauma refresher
      course, with scores approaching those of the expert teams.

PMID- 12045634
TI  - Two careers in one: an analysis of the earning power of certification in surgical
      critical care.
AB  - BACKGROUND: The core of general surgery supports multiple disciplines, each of
      which entails similar operative care for different diseases. The purpose of this
      study was to compare variations of practice patterns of four general surgeons to
      define the general surgical core that each shared in common, and to determine the
      effect of subspecialization in surgical critical care on the scope of practice
      and efficiency of revenue production. METHODS: The charges and collections of
      four members of the same surgical faculty were analyzed for the 6 months
      beginning July 1, 2000. Three members practiced general surgery with additional
      specialization in surgical oncology, surgical endoscopy, and trauma/critical
      care. The fourth covered all aspects of general surgery, including in-house
      trauma call, but not surgical critical care. Data were stratified by Current
      Procedural Terminology code and categorized as operative, bedside care (which
      included minor procedures), and evaluation/consultation care. Scope of practice
      was defined as the proportion of operative cases represented by the 10 most
      frequently performed procedures. General surgical core was defined as those cases
      that were preformed by all four surgeons at the same frequency. Efficiency of
      revenue generation was defined as collection rate for these procedures divided by
      the established, budgeted collection rate for each practitioner. All results were
      compared using chi(2) with significance accepted at p < 0.05. RESULTS: Fifteen
      operative procedures were performed with equal frequency by each surgeon and
      represented a broad spectrum of surgical disease. These procedures constituted a
      similar proportion of operative practice for all specialists (mean, 45.2%; 90%
      confidence limit, 3.5%), yet occupied 70% of the trauma surgeon's 10 most
      frequent surgical procedures versus 36% for the surgical oncology and surgical
      endoscopy. Charges generated by the provision of surgical critical care,
      especially in bedside procedures commonly performed in the intensive care unit,
      exceeded all of the other three surgeons and equaled the revenue generated by
      operative care. Although overall revenue-generating efficiency was less for the
      trauma surgeons (57% of eventual collections vs. 67%, chi(2) p = 0.1), immediate
      reimbursement for critical care was higher than for any other clinical services.
      CONCLUSION: These data demonstrate that subspecialization in surgical critical
      care provides valid additional earning capacity to surgical practitioners.
      Reimbursement is at least as good as for traditional operative care, and fees
      generated can actually exceed revenue from operative care. With impending
      decreases in global reimbursement, and attempts to unbundle operative fees, this
      additional capability becomes an important consideration in potential career
      choice, as well as a major component in the fiscal stability of trauma programs.

PMID- 12045635
TI  - The efficacy and limitations of transarterial embolization for severe hepatic
      injury.
AB  - BACKGROUND: The efficacy of transarterial embolization (TAE) for severe blunt
      hepatic injury has been reported. We performed a prospective study evaluating the
      efficacy and the limitation of TAE from January 1996 to December 2000. METHODS:
      All patients with blunt abdominal injury who could be stabilized by fluid
      resuscitation underwent computed tomographic (CT) scan examinations. Patients
      with CT scan evidence of hepatic injury were classified into five grades
      according to CT scan findings on the basis of the injury scale of the American
      Association for the Surgery of Trauma (Mirvis classification). All patients with
      CT scan grade 3 to 5 injury underwent angiography. When angiography showed
      extravasation of contrast medium extending from hepatic arterial branches, TAE
      was performed. RESULTS: Of 612 patients with blunt abdominal trauma, 51 had CT
      scan grade 3 to 5 injury. Thirty-seven of these patients had a CT scan grade 3
      injury and 18 underwent TAE. One of 19 patients who did not undergo TAE developed
      a delayed hemorrhage on day 6 and required a laparotomy. All 13 patients with a
      CT scan grade 4 injury had angiographic findings of the extravasation. TAE was
      successful in 11 patients and unsuccessful in 2. Five patients with a CT scan
      grade 4 injury required laparotomy. One developed a delayed hemorrhage on day 4.
      The remaining four patients had a major venous injury (a right lobectomy was
      performed in two with inferior vena cava injury, and a gauze packing in two with
      hepatic venous injury). One patient with a CT scan grade 5 injury underwent
      immediate laparotomy after TAE. Laparotomy revealed inferior vena cava injury and
      a right lobectomy was performed. Only two patients who underwent a lobectomy died
      of an uncontrollable hemorrhage. All CT scans of patients with hepatic venous or
      inferior vena cava injury showed a large low-density area (> or = 10 cm) with
      involvement of these vessels. The volumes of fluid resuscitation needed from
      admission until TAE ranged from 2,109 to 2,638 mL/h. CONCLUSION: It was
      considered that the combination of the presence of a CT scan grade 4 or 5 lesion
      and the fluid requirements of more than 2,000 mL/h to maintain normotension
      indicated the absolute necessity of surgery. We felt that these patients were not
      candidates for TAE, and should undergo immediate laparotomy.

PMID- 12045636
TI  - The need for early angiographic embolization in blunt liver injuries.
AB  - BACKGROUND: Although nonoperative management of blunt liver injury (BLI) has
      become standard practice, adjuncts to nonoperative therapy, such as angiographic
      embolization, have not been well characterized. METHODS: Patients with BLI were
      retrospectively identified at our American College of Surgeons-verified Level I
      trauma center from January 1997 through February 2001. Patients were stratified
      into four groups: those who received angiographic embolization (AE) as an early
      intervention when BLI was initially diagnosed (EARLY-AE); those who underwent AE
      after liver-related operation or later in the hospital course (LATE-AE); those
      treated with operation only (OR-ONLY); and nonoperative patients who also did not
      undergo AE (NO-OR). RESULTS: There were 126 patients with BLI, of whom 94 were NO
      OR, 20 were OR-ONLY, 6 had LATE-AE, and 6 had EARLY-AE. The NO-OR group had
      significantly lower liver Abbreviated Injury Scale scores. Liver Abbreviated
      Injury Scale scores were not different between the EARLY-AE, LATE-AE, and OR-ONLY
      groups. Liver-related mortality was not lower for those treated with AE. There
      was a trend toward lower mortality for just the EARLY-AE group compared with the
      LATE-AE and OR-ONLY groups (0% vs. 50% and 35%). The number of units of packed
      red blood cells transfused and the number of liver-related operations were lower
      in the EARLY-AE compared with the LATE-AE group, but liver-related complications
      were not different between the EARLY-AE, LATE-AE, or OR-ONLY groups. AE was
      successful in arresting hemorrhage in 83% of the cases. CONCLUSION: In this small
      series, we observed similar morbidity and mortality with AE compared with
      operative therapy. EARLY-AE did decrease blood use and the number of liver
      related operations. AE can be performed on severely injured patients with
      comparable liver-related mortality and complications. Further study of the timing
      of and outcomes from AE is needed.

PMID- 12045637
TI  - Hepatic angiography in patients undergoing damage control laparotomy.
AB  - OBJECTIVE: Patients undergoing damage control (DC) laparotomy require intensive
      and aggressive resuscitation, and may require additional maneuvers to control
      parenchymal bleeding. Those patients suffering significant liver injury are at
      high risk for arterial bleeding deep within the liver, and many require hepatic
      angiography in addition to hepatic packing. We reviewed our experience with
      hepatic angiography, and sought to determine its safety in the DC population of
      penetrating and blunt trauma patients. METHODS: A 3-year (June 1997-May 2000)
      retrospective review generated 37 DC patients. Patients sustaining hepatic trauma
      constituted the study group. Patients undergoing angiography in addition to DC
      laparotomy were compared with the group of patients not undergoing angiography.
      Data regarding mechanism of injury, patient demographics, extent of hepatic
      injury, and presence of associated injuries were collected. Physiologic
      parameters including vital signs at admission, lowest pH and base excess in the
      operating room, and lactate levels in the intensive care unit, as well as volumes
      of fluid resuscitation throughout all phases of DC were examined. Complications
      including death, intra-abdominal processes, acute respiratory distress syndrome
      and/or multiple organ dysfunction syndrome, and acute renal failure were
      reviewed. RESULTS: Nineteen patients (51%) had hepatic trauma and underwent
      perihepatic packing as a part of DC laparotomy. Eleven had sustained penetrating
      injury and 8 had blunt injury. There was 1 American Association for the Surgery
      of Trauma grade I, 5 grade II, 3 grade III, and 10 grade IV injuries. Nine
      patients in the study population underwent angiography, and eight of these were
      hepatic artery angiograms. One hepatic angiogram was obtained before operation
      and seven were obtained in the immediate postoperative period. Six underwent
      embolization of bleeding hepatic vessels, for a therapeutic liver angiography
      rate of 75%. There was no statistical difference in physiologic parameters or
      fluid requirements between the patients who underwent angiography and those who
      did not. There were no mishaps or complications from angiography or while in the
      angiography suite. CONCLUSION: Hepatic angiography is a safe adjunct to the
      principles of damage control. It has a high therapeutic ratio, with no
      significant untoward effect in this small study population.

PMID- 12045638
TI  - Comparative study of the hemostatic efficacy of a new human fibrin sealant: is an
      antifibrinolytic agent necessary?
AB  - BACKGROUND: Sustained hemostasis by fibrin sealant (FS) is critically important
      when it is used in trauma surgery. To purportedly delay fibrin degradation and
      prevent premature hemostatic failure, some FS products added an antifibrinolytic
      agent (e.g., bovine aprotinin). The purpose of this study was to compare the
      overall hemostatic efficacy of a new inhibitor-free FS obtained from the American
      Red Cross (ARC-FS) to a clinically available aprotinin-containing FS preparation
      (Tisseel). The need for addition of an antifibrinolytic agent was assessed under
      normal and high-fibrinolytic conditions. METHODS: The abdominal aortas of
      anesthetized rabbits were transected and anastomosed, end-to end, using only four
      interrupted sutures. The suture line was covered with approximately 2 mL of
      either type of FS and blood flow was restored. Blood loss was absorbed by gauze
      and measured. All rabbits were recovered and underwent histologic examination 4
      weeks after operation. The efficacy of FS was also tested under a high
      fibrinolytic state by treating the rabbits with human recombinant tissue
      plasminogen activator (0.15 mg/kg, 3-hour infusion). The investigators were
      blinded to the treatment groups. RESULTS: The majority (11 of 12) of deaths
      occurred because of bleeding at the suture line within 7 days of surgery.
      Sustained hemostasis by FS (>1 week) was required for normal tissue healing and
      long-term survival of animals. Application of ARC-FS to the suture line produced
      immediate hemostasis in 43% of animals (three of seven), with mean blood loss of
      4.8 +/- 1.8 mL, and 86% long-term survival. Tisseel application produced
      immediate hemostasis in 13% of animals (one of eight), with mean blood loss of
      26.9 +/- 7.0 mL (p < 0.05 vs. ARC-FS) and survival rate of 37% (three of eight).
      Under high-fibrinolytic conditions, ARC-FS produced immediate and complete
      hemostasis in seven of eight animals (88%), whereas the Tisseel demonstrated
      complete hemostasis in one of seven (p < 0.01). The ARC-FS rabbits had a blood
      loss of 1.9 +/- 1.9 mL and survival rate of 75% (six of eight), whereas the
      Tisseel animals had a mean blood loss of 30 +/- 6.0 mL and survival rate of 43%
      (three of seven) (p < 0.01). No detrimental effect on healing was noted with
      either product. CONCLUSION: ARC-FS provides effective and secure hemostasis
      against high-pressure arterial bleeding under both normal and high-fibrinolytic
      conditions. Addition of an antifibrinolytic agent such as aprotinin is not
      required to sustain the hemostatic function of this fibrin sealant.

PMID- 12045639
TI  - Injury rates among restrained drivers in motor vehicle collisions: the role of
      body habitus.
AB  - BACKGROUND: Previous studies have examined the independent effects of occupant
      height, obesity, and body mass index in motor vehicle collisions and identified
      related injury patterns. The hypothesis of this study was that as the driver's
      body habitus diverges from the 50% percentile male Hybrid III Crash Dummy (H3CD),
      the frequency of injury changes. METHODS: The 1995 to 1999 National Automotive
      Sampling System Crashworthiness Data System was used. Study entry was limited to
      restrained drivers who were then subdivided into height and weight categories.
      Incidence rates were calculated for injuries to selected body regions as defined
      by the Abbreviated Injury Scale for overall, frontal, and driver's side
      collisions. RESULTS: When grouped according to height and weight as descriptors
      of body habitus, injury rates for restrained drivers were increased as well as
      decreased in several subgroups. This association was seen in overall, frontal,
      and driver's side collisions. CONCLUSION: The H3CD plays a major role in
      vehicular cabin interior design and crash testing. For drivers with a body
      habitus different from that of the H3CD, the vehicle cabin/body fit changes and
      the safety features may perform differently, which could account for these
      observations.

PMID- 12045640
TI  - The effect of severe traumatic brain injury on the family.
AB  - BACKGROUND: The effects of traumatic brain injury on family dynamics and finances
      have not been extensively studied. We designed a 30-item survey to determine the
      effects of the injury on the child, parent(s), and siblings, and whether parents
      were retrospectively content with the decisions related to aggressiveness of
      care. METHODS: A questionnaire written on a sixth-grade reading level was mailed
      to 46 families of children who survived a traumatic brain injury resulting in an
      initial Glasgow Coma Scale score < or = 7. This is a descriptive study without
      statistical analysis. Human Studies Committee review and informed consent were
      obtained. RESULTS: Thirty-two of 46 (69.6%) surveys were completed by mail or
      telephone. Mean patient age at time of injury was 8.7 years, mean time since
      injury was 3 years, and mean Glasgow Coma Scale score was 3.7. Approximately one
      third of children have disabilities related to education, socialization, and/or
      self-care skills; require multiple health care visits each month; and require
      prescription medications. Over one third of families were impacted in a moderate
      to profoundly negative way; 30% of families reported a deterioration in finances
      or loss of job; and 16% reported a worsening of adult relationships. In 13 of 32
      cases, modification of current housing or new housing was required to facilitate
      home care. Siblings were adversely affected in approximately 16 of 28 families,
      exhibiting behavioral problems, increased fear, and withdrawal from the injured
      child. Only 1 of 32 families stated that they would have considered less
      aggressive treatment, even if it led to the child's death. CONCLUSION: Traumatic
      brain injury of a child had a negative impact on family dynamics and/or sibling
      behavior in more than one third of families. Despite this, most families would
      not limit or withdraw care if they could reconsider decisions regarding
      treatment. This information can be used to counsel families.

PMID- 12045641
TI  - Surgeon-performed focused assessment with sonography for trauma as an early
      screening tool for pregnancy after trauma.
AB  - BACKGROUND: Incidental pregnancy in trauma patients is associated with a high
      fetal mortality. Because of quality assurance reasons, many trauma centers have
      eliminated the rapid urine pregnancy screen. We sought to determine the utility
      and impact of the initial ultrasound examination in the diagnosis of pregnancy in
      female trauma patients. METHODS: Data were analyzed for all female trauma
      patients in whom pregnancy was diagnosed during a 5-year period. RESULTS: One
      hundred one (70%) of 144 pregnant women had an initial ultrasound examination.
      Eighteen patents had newly diagnosed pregnancies, of whom 8 of 9 patients (89%)
      at > or = 8 weeks' gestation were diagnosed by the initial ultrasound. This
      directly contributed to a significant decrease in the amount of radiation
      exposure (p < 0.001) compared with patients diagnosed by serum beta-human
      chorionic gonadotropin. CONCLUSION: An initial ultrasound examination should be
      considered in all female trauma patients of reproductive age. This may help to
      promote a reduction in fetal radiation exposure.

PMID- 12045642
TI  - Temporary intravascular shunt in complex extremity vascular injuries.
AB  - BACKGROUND: Early revascularization of ischemic limbs is an important step in the
      management of complex extremity vascular injuries (CEVIs). We present our
      experience of using a temporary intravascular shunt (TIVS) in the management of
      patients with limb-threatening vascular injuries. METHODS: Patients who had CEVIs
      at our institution from January 1996 to December 2000 were treated with early
      insertion of a TIVS at the initial phase of operations. The TIVSs were assembled
      from simple intravenous and extension tubes available in the operating room.
      Rigid stabilization of the injured bones and/or joints, debridement of the
      devitalized soft tissues, saphenous vein harvest for interposition grafts, and
      repair of any associated venous injuries were performed while the shunts were in
      place. Then, the shunts were removed and the injured arteries were repaired.
      RESULTS: There were five men and two women in this series. The preoperative time
      ranged from 120 to 450 minutes (median, 390 minutes). All TIVSs were inserted
      within the initial 30 minutes of operation. The injured arteries were popliteal
      (five patients), common femoral (one patient), and brachial arteries (one
      patient). Three patients also had associated venous injuries (i.e., two popliteal
      veins and one common femoral vein). Six injured arteries were repaired with
      reversed saphenous vein grafts and one (popliteal artery) was repaired by end-to
      end anastomosis. The shunt time ranged from 60 to 180 minutes (median, 120
      minutes). One patient had a TIVS inserted into both injured popliteal artery and
      vein. The operative time ranged from 225 to 360 minutes (median, 285 minutes). No
      complications related to shunt insertion were observed and all limbs could be
      salvaged. CONCLUSION: A self-constructed shunt is inexpensive, safe, and
      convenient to insert. Early revascularization of the injured limb with a TIVS can
      eliminate the adverse effects of prolonged ischemia and enables the surgeons to
      manage other associated injuries in an unhurried manner. We recommend early
      insertion of TIVSs in CEVIs.

PMID- 12045643
TI  - Intra-abdominal free fluid without solid organ injury in blunt abdominal trauma:
      an indication for laparotomy.
AB  - BACKGROUND: The optimal management of patients sustaining blunt abdominal trauma
      (BAT), in whom intra-abdominal free fluid but no solid organ injury is found on
      imaging, remains unclear. The purpose of this study was to determine the
      incidence and significance of this finding. METHODS: All patients presenting with
      suspected BAT to a provincial trauma center over a 30-month period were reviewed.
      A screening focused abdominal sonogram for trauma scan was obtained in every
      case. Stable patients with positive or indeterminate scans underwent computed
      tomographic scanning. Those with free fluid but without visible solid organ
      injury were studied. Radiologic interpretation, clinical management, and
      operative findings were analyzed. RESULTS: Twenty-eight of 1,367 patients (2%)
      met inclusion criteria. Twenty-one patients (75%) underwent exploratory
      laparotomy, which for 16 (76%) was therapeutic: bowel injuries were found in 10
      patients, mesentery injuries in 6, and injuries to solid organs in 3. In five
      patients, laparotomy was nontherapeutic. Those with more than a trace of free
      fluid were significantly more likely to have a therapeutic procedure. Seven
      patients (25%) were observed, of whom two failed nonoperative management and
      underwent therapeutic laparotomies within 24 hours of admission for missed colon,
      splenic, and hepatic injuries. The presence of abdominal seat belt bruising or a
      Chance-type fracture in the study patients was associated with a 90% and 100%
      therapeutic laparotomy rate, respectively. Computed tomographic scan findings
      were variable and were not able to predict injury severity or need for surgery.
      CONCLUSION: The finding of more than trace amounts of free fluid in the absence
      of solid organ injury in BAT is often associated with clinically significant
      visceral injury. Early laparotomy is recommended for these patients.

PMID- 12045644
TI  - Hypotensive resuscitation during active hemorrhage: impact on in-hospital
      mortality.
AB  - BACKGROUND: Traditional fluid resuscitation strategy in the actively hemorrhaging
      trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP).
      One human trial has demonstrated improved survival when fluid resuscitation is
      restricted, whereas numerous laboratory studies have reported improved survival
      when resuscitation is directed to a lower than normal pressure. We hypothesized
      that fluid resuscitation titrated to a lower than normal SBP during the period of
      active hemorrhage would improve survival in trauma patients presenting to the
      hospital in hemorrhagic shock. METHODS: Patients presenting in hemorrhagic shock
      were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm
      Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to
      this endpoint until definitive hemostasis was achieved. In-hospital mortality,
      injury severity, and probability of survival were determined for each patient.
      RESULTS: One hundred ten patients were enrolled over 20 months, 55 in each group.
      The study cohort had a mean age of 31 years, and consisted of 79% male patients
      and 51% penetrating trauma victims. There was a significant difference in SBP
      observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury
      Severity Score (19.65 +/- 11.8 vs. 23.64 +/- 13.8, p = 0.11) and the duration of
      active hemorrhage (2.97 +/- 1.75 hours vs. 2.57 +/- 1.46 hours, p = 0.20) were
      not different between groups. Overall survival was 92.7%, with four deaths in
      each group. CONCLUSION: Titration of initial fluid therapy to a lower than normal
      SBP during active hemorrhage did not affect mortality in this study. Reasons for
      the decreased overall mortality and the lack of differentiation between groups
      likely include improvements in diagnostic and therapeutic technology, the
      heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a
      marker for tissue oxygen delivery.

PMID- 12045645
TI  - Fluid resuscitation improves hemodynamics without increased bleeding in a model
      of uncontrolled hemorrhage induced by an iliac artery tear in dogs.
AB  - BACKGROUND: Fluid resuscitation administered before hemorrhage control for trauma
      victims sustaining penetrating abdominal injury is controversial. Our objective
      was to evaluate intra-abdominal blood loss and hemodynamic and metabolic effects
      of no fluid resuscitation, small-volume 7.5% sodium chloride/6% dextran-70 (HSD),
      or large-volume lactated Ringer's (LR) solution during intra-abdominal vascular
      injury and uncontrolled hemorrhage. METHODS: In pentobarbital-anesthetized dogs
      (n = 26, 17 +/- 0.3 kg), a suture was placed through the common iliac artery to
      produce a 3-mm tear when the exteriorized suture lines were pulled after incision
      closure. Dogs were randomized to three groups, according to the treatment used
      after 20 minutes of uncontrolled hemorrhage: controls, no fluid resuscitation (CT
      group) (n = 6); the HSD group (4 mL/kg over 4 minutes, n = 6); and the LR group
      (32 mL/kg over 15 minutes, n = 6). After 40 minutes of uncontrolled bleeding,
      animals were killed, and intra-abdominal blood loss was measured. RESULTS: Eight
      dogs died from severe hemorrhagic shock before randomization and were excluded.
      After 20 minutes, animals presented lower blood pressure (approximately 35 mm
      Hg), low cardiac output (approximately 1.0 L/min/m(2)), and metabolic acidosis
      (pH approximately 7.23, base excess approximately -9 mmol/L). After HSD and LR
      solution, arterial pressure presented a transient increase, but remained below
      baseline. Two animals died before the end of the experiment, both in the LR
      group. Cardiac index was partially improved in the LR and HSD groups, whereas the
      CT group sustained a low-flow state. There were no significant differences
      between groups regarding intra-abdominal blood loss (CT group, 47.8 +/- 5.9
      mL/kg; HSD group, 41.7 +/- 2.3 mL/kg; and LR group, 49.4 +/- 0.7 mL/kg).
      CONCLUSION: Fluid resuscitation with either large-volume LR solution or small
      volume HSD, during uncontrolled hemorrhage from intra-abdominal vascular injury,
      produced hemodynamic and metabolic benefits, without additional blood loss,
      whereas no fluid resuscitation was associated with sustained low cardiac output
      and hypotension.

PMID- 12045646
TI  - Validation of new trauma triage rules for trauma attending response to the
      emergency department.
AB  - INTRODUCTION: The American College of Surgeons Committee on Trauma has suggested
      triage criteria for the immediate attendance of a trauma surgeon to an injured
      patient in the emergency department. This study validates the accuracy of these
      criteria in identifying high-risk trauma patients and assesses the impact of
      trauma surgeon response time. METHODS: A study group of trauma patients with a
      systolic blood pressure (SBP) < 90 mm Hg, Glasgow Coma Scale (GCS) score < 8,
      airway compromise managed with endotracheal intubation (ETI) or surgical airway,
      or gunshot wound (GSW) to the neck or torso were compared with a control group of
      patients meeting none of these criteria. Outcome measurements included Injury
      Severity Score (ISS), duration of hospitalization (length of stay [LOS]),
      intensive care unit (ICU) days, direct transfer to the ICU or operating room, and
      mortality. For the study group, trauma surgeon response times, < or = 15 minutes
      and > 15 minutes, were compared for age, ISS, LOS, ICU days, mortality, and
      direct transfer to the ICU or operating room. Statistical analysis was performed
      using the t test and the Yates-corrected chi(2) test (p < 0.05), with odds ratios
      calculated on the basis of trauma activation criteria and outcome measures.
      Multiple logistic regression was used to assess the relation between the
      independent variables SBP, GCS, ETI, and GSW with direct transfer to the ICU or
      operating room and mortality. RESULTS: A total of 4,910 patients were identified,
      including 791 study group patients. The mean ISS, LOS, ICU days, and mortality
      were significantly higher in the study group (p < 0.01). Odds ratios of the study
      group for direct transfer to the ICU or operating room were 91 and 2 for ETI, 23
      and 1.4 for GCS score < 8, 8 and 2.2 for GSW, and 7 and 1.6 for SBP < 90 mm Hg,
      respectively. The odds ratios for mortality were 39 for ETI, 104 for GCS score <
      8, 12 for GSW, and 74 for SBP < 90 mm Hg. Regression analysis demonstrated that
      GSW, SBP < 90 mm Hg, and ETI predicted ICU admission; GSW, SBP < 90 mm Hg, and
      ETI predicted operative intervention; and GCS score < 8, SBP < 90 mm Hg, and ETI
      were associated with mortality. Trauma surgeon response times were available for
      658 (83%) of the study group patients. No significant differences were found
      between the two response groups. CONCLUSION: Trauma patients meeting the triage
      criteria proposed by the American College of Surgeons Committee on Trauma have
      more severe injuries, a higher mortality rate, and longer hospital and ICU stays
      than control patients. SBP < 90 mm Hg, ETI, and GSW are predictive of urgent
      operating room use and ICU admission. A significantly higher mortality rate is
      associated with SBP < 90 mm Hg, ETI, and GCS score < 8. Incorporating these
      criteria into trauma center triage rules to identify high-risk injured patients
      is warranted. However, trauma surgeon response time < or = 15 minutes was not
      associated with improved patient outcome, and optimal response time remains
      uncertain.

PMID- 12045647
TI  - Standardized outcome evaluation after blunt multiple injuries by scoring systems:
      a clinical follow-up investigation 2 years after injury.
AB  - OBJECTIVE: The objective of this study was to evaluate the state of
      rehabilitation in patients with blunt multiple injuries 2 years after their
      initial injuries, using several standardized scales and a recently described
      comprehensive scoring system, by means of a prospective clinical multicenter
      study. METHODS: Two years after the initial injury, patients with blunt multiple
      injuries (Injury Severity Score > or = 16) underwent a clinical follow-up in 5
      German Level I trauma centers. The reassessment included a complete head-to-toe
      examination of the musculoskeletal system and a neurologic examination. The
      following patient-assessed health status scores were used to determine the
      quality of life: Short-Form 12, Functional Independence Measurement, and
      Musculoskeletal Function Assessment. Moreover, a comprehensive scoring system
      developed in our department (Hannover Score for Polytrauma Outcome [HASPOC]) was
      used that includes provider-report (physician's examination) and self-report
      (score systems) criteria. RESULTS: Two hundred fifty-four of 312 patients who had
      been injured between January 1995 and July 1996 were reexamined between January
      1, 1997, and July 1, 1998. Among the remaining 58 patients, 9 had died by the
      time of follow-up, and 49 patients had not accepted the invitation. The mean age
      of those patients who underwent reexamination was 36 +/- 13 years, the mean
      Injury Severity Score was 24 +/- 6, and the mean initial Glasgow Coma Scale score
      was 11 +/- 4 (Abbreviated Injury Scale (AIS) head score of 3.3 +/- 1.1; AIS face,
      1.4 +/- 0.1; AIS chest, 3.0 +/- 0.8; AIS abdomen, 1.7 +/- 0.6; and AIS
      extremities, 3.4 +/- 0.8). The general outcome (Short-Form 12) was as follows:
      grade I, 9%; grade II, 25%; grade III, 29%; grade IV, 25%; grade V, 6%; and grade
      VI, 6%. The outcome of the injured extremity demonstrated moderate or severe
      restrictions according to the Musculoskeletal Function Assessment in 41% of
      injuries of the lower extremity and in 16% of injuries of the upper extremity.
      Among patients with injuries to the lower extremity, 52% experienced pain or
      impaired ability to walk related to an injury of the foot or ankle, 31% indicated
      pain after a knee or thigh injury, and 27% indicated pain after a femoral or hip
      injury. The most severe deficits in the range of motion occurred in the foot and
      the ankle region (13.4% deficit of range of motion < 20% of normal range, p <
      0.05 to other injuries). The results of the outcome obtained by self-report
      correlated with the clinical examination when a scoring system was used that was
      described recently, the HASPOC. CONCLUSION: In a standardized multicenter
      reexamination of patients with blunt multiple injuries, the general outcome was
      usually fair or good. Both the complaints and the objective results of specific
      extremity areas demonstrated that most limitations were because of injuries below
      the knee. These results were adequately reflected by a comprehensive scoring
      system, combining self-report and provider report (HASPOC).

PMID- 12045648
TI  - A simplified approach to the diagnosis of elevated intra-abdominal pressure.
AB  - BACKGROUND: Previous methods described to measure bladder pressure require
      additional setup, making these techniques complex and time consuming. We describe
      a simple U-tube technique and investigate its accuracy for measuring intra
      abdominal pressure (IAP). METHODS: Warm saline was infused into the peritoneum of
      five pigs to increase IAP. Indirect methods of measuring IAP included bladder,
      inferior vena cava (IVC), and gastric pressures. Bladder pressure was measured by
      both the standard and U-tube technique. IVC pressure was measured via a femoral
      line and gastric pressure was transduced through an orogastric tube. In addition,
      30 patients undergoing laparoscopy were prospectively investigated. Insufflated
      abdominal pressure readings were obtained and compared with bladder pressures
      measured by the U-tube technique (n = 20) and standard technique (n = 10).
      RESULTS: In the animal study, U-tube manometry had the highest degree of
      correlation (r(2) = 0.98) and the lowest bias (0.51 +/- 1.63 mm Hg). The bladder
      pressure measured by the U-tube technique was between 0.1 and 0.9 mm Hg less than
      the directly measured IAP (95% confidence interval). There was a high degree of
      correlation between IAP and the standard technique for bladder pressure (r(2) =
      0.93), IVC pressure (r(2) = 0.93), and gastric pressure (r(2) = 0.90). Strong
      correlation also existed between the U-tube and standard techniques for measuring
      bladder pressure (r(2) = 0.96). In humans, a strong correlation between
      insufflated abdominal pressure and bladder pressure (U-tube technique, r(2) =
      0.79; standard technique, r(2) = 0.53) was also encountered. CONCLUSION: The
      accuracy of the U-tube manometry technique for measuring intra-abdominal pressure
      is comparable to previously described techniques. The U-tube technique is simple,
      does not require additional equipment, and can be performed by any member of the
      medical team.

PMID- 12045649
TI  - Acute traumatic rupture of the thoracic aorta treated with endoluminal stent
      grafts.
AB  - BACKGROUND: Endovascular technologies provide a new therapeutic option in the
      treatment for acute traumatic rupture of the thoracic aorta. We report our
      experience with endoluminal stent graft repair of thoracic aortic ruptures.
      METHODS: Five patients underwent repair of the thoracic aorta with an endoluminal
      stent graft for acute traumatic rupture. Data from patient history, the
      procedure, hospital course, and follow-up were analyzed. RESULTS: All patient
      were involved in motor vehicle crashes. The mean Injury Severity Score was 51.8
      +/- 6.38. All procedures were technically successful. Mean operating room time
      was 111 minutes and mean estimated blood loss was 200 mL. There were no cases of
      postprocedural endoleaks or conversions. There were no procedural complications,
      paraplegia, or deaths. Average follow-up was 20.2 months. CONCLUSION: Five cases
      of successful endograft repair of thoracic aortic rupture have been demonstrated.
      This should encourage future studies to determine whether endovascular repair of
      thoracic aortic ruptures is a safe and feasible alternative to conventional open
      repair.

PMID- 12045650
TI  - Influence of gut microflora on mesenteric lymph cytokine production in rats with
      hemorrhagic shock.
AB  - OBJECTIVE: The aim of the present study was to test the hypothesis that the
      resident gut microflora play a role in modulating gut cytokine production under
      normal circumstances and in response to tissue injury with or without hemorrhagic
      shock. METHODS: The postnodal lymph was collected from the main mesenteric
      lymphatic channel 1 hour before, during (1.5 hours), and hourly for 6 hours after
      90 minutes of sham or actual hemorrhagic shock (30 mm Hg) in the following three
      groups of rats, all of which had laparotomies and vascular instrumentation: rats
      with a normal gut flora (NF), rats whose gut flora had been decontaminated with
      oral antibiotics (AD), and rats with Escherichia coli C25 intestinal overgrowth
      (MA). Interleukin (IL)-6 and TNF levels in the mesenteric lymph were measured
      using cytokine-dependent cellular assays. Endotoxin levels and endotoxin
      neutralizing capacity in the lymph were also measured. RESULTS: Mesenteric lymph
      IL-6 levels in the laparotomized MA-sham animals were significantly elevated
      compared with NF-sham animals at 2 to 4 hours (p < 0.05) and at 5 and 6 hours
      after sham shock (p < 0.01). Similarly, IL-6 levels in laparotomized AD-shock
      animals were increased when compared with NF-shock animals 3 hours after shock (p
      < 0.001). Lymph tumor necrosis factor bioactivity, although present in all
      surgically manipulated groups, was scarcely detectable in untouched animals.
      Endotoxin-neutralizing capacity was significantly impaired in shocked animals
      compared with untouched animals. CONCLUSION: Changes in the gut microflora
      modulate the gut cytokine production after tissue injury with or without
      hemorrhagic shock, with intestinal bacterial overgrowth leading to the greatest
      increase in mesenteric lymph IL-6 levels.

PMID- 12045651
TI  - Bilateral vertebral artery dissection after blunt cervical trauma: case report
      and review of the literature.

PMID- 12045652
TI  - Penetrating injury of the temporal fossa with a screwdriver with associated
      traumatic optic neuropathy.

PMID- 12045653
TI  - Complex penetrating cranial base trauma: case report demonstrating
      multidisciplinary management.

PMID- 12045654
TI  - Detection of indolent infection at the time of revision fracture surgery.

PMID- 12045655
TI  - Predictors of compliance with the evidence-based guidelines for traumatic brain
      injury care: a survey of United States trauma centers.
AB  - BACKGROUND: In 1995, evidence-based guidelines for the management of severe
      traumatic brain injury (TBI) were published and disseminated. Information
      regarding their implementation is limited. METHODS: During 1999 to 2000, we
      contacted all designated U.S. trauma centers caring for adults with severe TBI to
      determine the degree of guideline compliance and to identify predictors. RESULTS:
      Of 924 centers identified, 828 participated (90%). Four hundred thirty-three with
      intensive care units caring for severe TBI were surveyed. Three hundred ninety
      five centers transferring patients were excluded. Full guideline compliance was
      rare (n = 68 [16%]). In multivariate analyses, treatment protocols (odds ratio
      [OR], 3.6; 95% confidence interval [CI], 1.9-6.6), neurosurgery residency program
      (OR, 5.0; 95% CI, 2.6-9.8), and state (OR, 2.7; 95% CI, 0.62-12) or American
      College of Surgeons (OR, 5.1; 95% CI, 1.1-23) designation increased the
      likelihood of full compliance versus noncompliance. CONCLUSION: Although evidence
      based guidelines were published and disseminated in 1995, implementation is
      infrequent. Focus must turn to changing physician practice and transport
      decisions to provide guideline-compliant care and improve patient outcome.

PMID- 12045657
TI  - A plea for uniformity in EMS research.

PMID- 12045656
TI  - Current concepts in posttraumatic osteomyelitis: a diagnostic challenge with new
      imaging options.

PMID- 12045658
TI  - Intraluminal aortic fat as an unusual presentation of blunt traumatic aortic
      rupture.

PMID- 12045659
TI  - Traumatic rupture of the aorta: repair with a covered endovascular stent.

PMID- 12045660
TI  - Impact of age of transfused blood in the trauma patient.

PMID- 12045661
TI  - Role of mitogen- and stress-activated kinases in ischemic injury.
AB  - Protein kinase-mediated signaling cascades constitute the major route by which
      cells respond to their extracellular environment. Of these, three well
      characterized mitogen-activated protein kinase (MAPK) signaling pathways are
      those that use the extracellular signal-regulated kinase (ERK1/2) or the stress
      activated protein kinase (p38/SAPK2 or JNK/SAPK) pathways. Mitogenic stimulation
      of the MAPK-ERK1/2 pathway modulates the activity of many transcription factors,
      leading to biological responses such as proliferation and differentiation. In
      contrast, the p38/SAPK2 and JNK/SAPK (c-Jun amino-terminal kinase/stress
      activated protein kinase) pathways are only weakly, if at all, activated by
      mitogens, but are strongly activated by stress stimuli. There is now a growing
      body of evidence showing that these kinase signaling pathways become activated
      following a variety of injury stimuli including focal cerebral ischemia. Whether
      their activation, however, is merely an epiphenomenon of the process of cell
      death, or is actually involved in the mechanisms underlying ischemia-induced
      degeneration, remains to be fully understood. This review provides an overview of
      the current understanding of kinase pathway activation following cerebral
      ischemia and discusses the evidence supporting a role for these kinases in the
      mechanisms underlying ischemia-induced cell death.

PMID- 12045662
TI  - Tissue-type plasminogen activator has paradoxical roles in focal cerebral
      ischemic injury by thrombotic middle cerebral artery occlusion with mild or
      severe photochemical damage in mice.
AB  - The role of endogenous tissue-type plasminogen activator (tPA) in focal cerebral
      ischemic injury (FCII) after middle cerebral artery occlusion was studied using
      tPA gene-deficient (KO) mice and their wild-type (WT) littermates. The middle
      cerebral artery was occluded by thrombi induced by three different intensities of
      photochemical damage, a method that was newly introduced in mice. In both WT and
      KO mice, the intensity-dependent increase of FCII size was observed. The FCII
      size in tPA WT mice was smaller than in KO mice in cases of mild damage, whereas
      the FCII size was larger in WT mice than in KO mice in cases of severe damage.
      There was no difference in FCII size between WT and KO mice in cases of moderate
      damage. The number of microthrombi also increased with damage intensity in both
      WT and KO mice, but was less in WT mice at all intensities of damage. The results
      support the validity of the model of thrombotic occlusion by photochemical damage
      in mice, and suggest that endogenous tPA protects FCII through thrombolytic
      action on transient occlusion of middle cerebral artery with mild damage, but
      deteriorates on persistent occlusion with severe damage.

PMID- 12045663
TI  - Magnetic resonance angiography of thromboembolic stroke in rats: indicator of
      recanalization probability and tissue survival after recombinant tissue
      plasminogen activator treatment.
AB  - Magnetic resonance angiography (MRA) was performed in a thromboembolic stroke
      model of the rat to characterize intracranial vessel occlusion patterns and to
      test its predictive power for tissue recovery after recombinant tissue
      plasminogen activator (rt-PA) treatment. After rt-PA-treated selective middle
      cerebral artery (MCA) occlusion, full recanalization was observed in two of three
      animals, whereas additional occlusion of the circle of Willis (CW) resulted in
      full vascular flow restitution in only one of six rats. Tissue reperfusion
      markedly lagged the onset of treatment, and the delay correlated with the pattern
      of vessel occlusion (20 to 23 minutes for selective MCA occlusion vs. 71 to 79
      minutes for combined MCA/CW occlusion). In lateral cortex and striatum the
      apparent diffusion coefficient decreased to 78 +/- 15% of control after
      embolization, recovered to 80% to 85% after rt-PA treatment of selective MCA
      occlusion, but further declined to 66% to 69% after combined MCA/CW occlusion.
      Correspondingly, T2 relaxation time increased to 107% to 118% of control after
      selective MCA occlusion and to 112% to 124% after combined MCA/CW occlusion in
      these regions. The present investigation shows that MRA provides valuable
      information on the severity of thromboembolic stroke and has the power to
      predict, before the initiation of treatment, the functional tissue outcome after
      rt-PA-induced thrombolysis.

PMID- 12045664
TI  - Moment analysis of microflow histogram in focal ischemic lesion to evaluate
      microvascular derangement after small pial arterial occlusion in rats.
AB  - The authors' high-spatial-resolution optical method was used to examine
      microvascular derangement in a focal cerebral cortex lesion in 12 Sprague-Dawley
      rats anesthetized with alpha-chloralose-urethane. A pial artery (approximately 40
      to 50 microm diameter) was occluded by laser-beam cauterization (n = 6). Diluted
      carbon black suspension was injected into the internal carotid artery, and images
      in a 2-mm x 2-mm region of interest during tissue dye-dilution were recorded.
      Sequential frames were analyzed with Matlab software to evaluate blood
      distribution and mean transit time, affording a two-dimensional microflow map and
      histogram with first, second, third, and fourth moments. In the early phase of
      ischemia, blood distribution and average flow decreased (both P < 0.01), and the
      second moment (microflow heterogeneity) and third moment (skew to the left owing
      to increase in low-flow components) increased (P < 0.05 and P < 0.01,
      respectively). At approximately 2 hours, blood distribution decreased further in
      3 cases, apparently because capillary stasis prevented carbon black filling.
      However, average microflow unexpectedly increased in 4 of 5 rats, presumably due
      to exclusion of unperfused (low flow at the earlier stage) channels from the
      calculation. The authors conclude that flow in ischemic tissue is quite
      heterogeneous and that an averaged flow value tends to smear important
      information about ischemic microvascular derangement.

PMID- 12045665
TI  - Hemodynamic response in the unanesthetized rat: intrinsic optical imaging and
      spectroscopy of the barrel cortex.
AB  - Optical imaging spectroscopy was used to measure the hemodynamic response of
      somatosensory cortex to stimulation of the whiskers. Responses to brief puffs of
      air were compared in anesthetized and unanesthetized rats. The hemodynamic
      response was approximately four times larger in the unanesthetized animal than
      the corresponding anesthetized animal. In unanesthetized animals, a short-latency
      (approximately 400 milliseconds) short-duration (approximately 300 milliseconds)
      hemodynamic startle response was observed. General linear model analysis was used
      to extract this component from the time series, and revealed an underlying short
      latency increase in deoxygenated hemoglobin in response to somatosensory
      stimulation. It is proposed that anesthesia can have a marked affect on the
      relation between changes in blood volume and blood flow. This work represents a
      step in the development of an experimental model that can be used to investigate
      fundamental neurologic processes in the awake-behaving rodent.

PMID- 12045666
TI  - Nitric oxide formation during cortical spreading depression is critical for rapid
      subsequent recovery of ionic homeostasis.
AB  - Cortical spreading depression (CSD) is a temporary disruption of local ionic
      homeostasis that propagates slowly across the cerebral cortex. Cortical spreading
      depression promotes lesion progression in experimental stroke, and may contribute
      to the initiation of migraine attacks. The purpose of this study was to
      investigate the roles of the marked increase of nitric oxide (NO) formation that
      occurs with CSD. Microdialysis electrodes were implanted in the cortex of
      anesthetized rats to perform the following operations within the same region: (1)
      elicitation of CSD by perfusion of high K+ medium; (2) recording of CSD
      elicitation; (3) application of the NO synthase inhibitor, NG-nitro-l-arginine
      methyl ester (l-NAME); and (4) recording of dialysate pH changes. The primary
      effect of l-NAME (0.3 to 3.0 mmol/L in the perfusion medium) was a marked
      widening of individual CSD wave, resulting essentially from a delayed initiation
      of the repolarization phase. This change was due to NO synthase inhibition
      because it was not observed with the inactive isomer d-NAME, and was reversed by
      l-arginine. This effect did not appear to be linked to the suppression of a
      sustained, NO-mediated vascular change associated with the superposition of NO
      synthase inhibition on high levels of extracellular K+. The delayed initiation of
      repolarization with local NO synthase inhibition may reflect the suppression of
      NO-mediated negative feedback mechanisms acting on neuronal or glial processes
      involved in CSD genesis. However, the possible abrogation of a very brief, NO
      mediated vascular change associated with the early phase of CSD cannot be ruled
      out.

PMID- 12045667
TI  - Hypoxia-inducible factor-1alpha accumulation in the brain after experimental
      intracerebral hemorrhage.
AB  - Hypoxia-inducible factor-1 (HIF-1), a transcription factor composed of HIF-1alpha
      and HIF-1beta protein subunits, has been implicated in cellular protection and
      cell death in cerebral ischemia. The extent to which HIF-1 plays a role in brain
      pathology during intracerebral hemorrhage (ICH) is unknown. This study determined
      whether HIF-1alpha is upregulated at different time points in a rat model of ICH
      and the role of thrombin and red blood cell lysis in upregulation. Recently,
      thrombin has been implicated as a nonhypoxic regulator of HIF-1alpha in cultured
      smooth-muscle cells. Male Sprague-Dawley rats received intracerebral infusions of
      saline, autologous whole blood, blood plus hirudin, thrombin, thrombin plus
      hirudin, or lysed erythrocytes. Rats were killed at different time points for
      Western blot analysis, immunohistochemistry, immunofluorescent double staining,
      and reverse transcription polymerase chain reaction measurements of HIF-1alpha.
      HIF-1alpha protein levels increased without changing HIF-1alpha messenger RNA
      levels after intracerebral infusions of blood, thrombin, and lysed erythrocytes.
      HIF-1alpha positive cells, which proved to be neurons, were found in the brain
      after ICH. Hirudin, a specific thrombin inhibitor, reduced HIF-1alpha
      upregulation in response to both thrombin and blood. This study demonstrates that
      perihematomal HIF-1alpha protein is upregulated after ICH. This phenomenon is an
      early response of brain parenchyma to the clot. Thrombin and erythrocyte lysate
      are involved in HIF-1alpha upregulation through reducing HIF-1alpha degradation.

PMID- 12045668
TI  - Comet assay as a novel approach for studying DNA damage in focal cerebral
      ischemia: differential effects of NMDA receptor antagonists and poly(ADP-ribose)
      polymerase inhibitors.
AB  - The single-cell gel electrophoresis (comet assay) was used to evaluate the
      possibility of detecting single-strand breaks of brain DNA in the early phase of
      ischemia. Four hours after occlusion of the middle cerebral artery (MCAO) in
      rats, the percentage of DNA migrating into the comet tail (indicating the
      presence of breaks) increased from 11.4 +/- 4.70 to 34.7 +/- 9.2 (means +/- SD)
      in the caudate and from 9.9 +/- 4.3 to 42.8 +/- 14.1 in the cortex.
      Interestingly, a subpopulation of cells exhibiting higher resistance to the
      ischemic insult was present in the caudate putamen, but not in the cortex.
      Administration of MK801, an N-methyl-d-aspartate (NMDA) glutamate receptor
      antagonist, (1 mg/kg subcutaneously, 10 minutes before MCAO), reduced the
      ischemia-induced DNA breaks and the infarct volume, suggesting that excessive
      stimulation of NMDA receptors contributes to the formation of both DNA damage and
      infarct volume. In contrast, DPQ, an inhibitor of poly(ADP-ribose) polymerase
      (PARP) (10 mg/kg intraperitoneally, 2 hours before and 1 hour after MCAO),
      reduced the infarct volume but not DNA damage, suggesting that the
      neuroprotective actions of PARP inhibitors occur at a later step of the processes
      leading to postischemic neuronal death.

PMID- 12045669
TI  - Selective proteasomal dysfunction in the hippocampal CA1 region after transient
      forebrain ischemia.
AB  - Delayed neuronal death in the hippocampal CA1 region after transient forebrain
      ischemia may share its underlying mechanism with neurodegeneration and other
      modes of neuronal death. The precise mechanism, however, remains unknown. In the
      postischemic hippocampus, conjugated ubiquitin accumulates and free ubiquitin is
      depleted, suggesting impaired proteasome function. The authors measured regional
      proteasome activity after transient forebrain ischemia in male Mongolian gerbils.
      At 30 minutes after ischemia, proteasome activity was 40% of normal in the
      frontal cortex and hippocampus. After 2 hours of reperfusion, it had returned to
      normal levels in the frontal cortex, CA3 region, and dentate gyrus, but remained
      low for up to 48 hours in the CA1 region. Thus, the 26S proteasome was globally
      impaired in the forebrain during transient ischemia and failed to recover only in
      the CA1 region after reperfusion. The authors also measured 20S and 26S
      proteasome activities directly after decapitation ischemia (at 5 and 20 minutes)
      by fractionating the extracts with glycerol gradient centrifugation. Without
      adenosine triphosphate (ATP), only 20S proteasome activity was detected in
      extracts from both the hippocampus and frontal cortex. When the extracts were
      incubated with ATP in an ATP-regenerating system, 26S proteasome activity
      recovered almost fully in the frontal cortex but only partially in the
      hippocampus. Thus, after transient forebrain ischemia, ATP-dependent
      reassociation of the 20S catalytic and PA700 regulatory subunits to form the
      active 26S proteasome is severely and specifically impaired in the hippocampus.
      The irreversible loss of proteasome function underlies the delayed neuronal death
      induced by transient forebrain ischemia in the hippocampal CA1 region.

PMID- 12045670
TI  - Astrocytic activation and delayed infarct expansion after permanent focal
      ischemia in rats. Part I: enhanced astrocytic synthesis of s-100beta in the
      periinfarct area precedes delayed infarct expansion.
AB  - An astrocytic protein S-100beta enhances the expression of inducible nitric oxide
      synthase in cultured astrocytes at micromolar concentrations, leading to nitric
      oxide-mediated death of cocultured neurons. The present study examined whether S
      100beta production by reactive astrocytes accumulating within the periinfarct
      area was related to delayed expansion of infarct volume after permanent middle
      cerebral artery occlusion in the rat. After rapid increases during the initial 24
      hours, the increase of infarct volume then decelerated while maintaining the
      increasing tendency until 168 hours in this model, attaining a significant
      difference compared with that at 24 hours. In the periinfarct area, the number of
      reactive astrocytes expressing both S-100 and glial fibrillary acidic protein,
      the tissue level of S-100beta as measured by the sandwich enzyme-linked
      immunosolvent assay method using anti-S-100beta monoclonal antibody, and the
      number of terminal deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;
      triphosphate-biotin nick end labeling-positive cells were significantly increased
      preceding the delayed expansion of infarct volume. The CSF concentration of S
      100beta showed a biphasic increase, presumably reflecting the immediate release
      from astrocytes within the ischemic core and the subsequent production in
      reactive astrocytes within the periinfarct area. These results show for the first
      time that the enhanced synthesis of S-100beta by reactive astrocytes participates
      in the inflammatory responses within the periinfarct area, which may be related
      to the occurrence of delayed infarct expansion as a major component of the
      cytokine network.

PMID- 12045671
TI  - Astrocytic activation and delayed infarct expansion after permanent focal
      ischemia in rats. Part II: suppression of astrocytic activation by a novel agent
      (R)-(-)-2-propyloctanoic acid (ONO-2506) leads to mitigation of delayed infarct
      expansion and early improvement of neurologic deficits.
AB  - A novel agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), has a unique property in
      that it modulates functions of activated cultured astrocytes, including
      pronounced inhibition of S-100beta synthesis. The present study examined whether
      administration of this agent would mitigate the delayed expansion of infarct
      volume and the neurologic deficits after permanent middle cerebral artery
      occlusion (pMCAO) in rats. Daily intravenous administration of ONO-2506 (10
      mg/kg) abolished the delayed infarct expansion between 24 and 168 hours after
      pMCAO, whereas the acute infarct expansion until 24 hours was unaffected. The
      agent significantly reduced the expression of S-100beta and glial fibrillary
      acidic protein in the activated astrocytes and the number of terminal
      deoxynucleotidyl transferase-mediated 2;-deoxyuridine 5;-triphosphate-biotin nick
      end labeling-positive cells in the periinfarct area. The neurologic deficits were
      significantly improved, compared with the vehicle-treated groups, as early as 24
      hours after the initial administration of ONO-2506. The agent had a wide
      therapeutic time window of 0 to 48 hours after pMCAO. These results indicate that
      because of the pharmacologic modulation of astrocytic activation induced by ONO
      2506, symptoms can regress whereas delayed expansion of the lesion is arrested.
      Pharmacologic modulation of astrocytic activation may confer a novel therapeutic
      strategy against stroke.

PMID- 12045672
TI  - Correlation between cerebral blood flow, substrate delivery, and metabolism in
      head injury: a combined microdialysis and triple oxygen positron emission
      tomography study.
AB  - Microdialysis continuously monitors the chemistry of a small focal volume of the
      cerebral extracellular space. Conversely, positron emission tomography (PET)
      establishes metabolism of the whole brain, but only for the duration of the scan.
      The objective of this study was to apply both techniques to head-injured patients
      simultaneously to assess the relation between microdialysis (glucose, lactate,
      lactate/pyruvate [L/P] ratio, and glutamate) and PET (cerebral blood flow [CBF],
      cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic
      rate of oxygen) parameters. Microdialysis catheters were inserted into the
      frontal cerebral cortex and adipose tissue of the anterior abdominal wall of 17
      severely head-injured patients. Microdialysis was performed during PET scans,
      with regions of interest defined by the location of the microdialysis catheter
      membrane. An intervention (hyperventilation) was performed in 13 patients. The
      results showed that combining PET and microdialysis to monitor metabolism in
      ventilated patients is feasible and safe, although logistically complex. There
      was a significant relation between the L/P ratio and the OEF (Spearman r = 0.69,
      P = 0.002). There was no significant relation between CBF and the microdialysis
      parameters. Moderate short-term hyperventilation appeared to be tolerated in
      terms of brain chemistry, although no areas were sampled by microdialysis where
      the OEF exceeded 70%. Hyperventilation causing a reduction of the arterial carbon
      dioxide tension by 0.9 kPa resulted in a significant elevation of the OEF, in
      association with a reduction in glucose, but no significant elevation in the L/P
      ratio or glutamate.

PMID- 12045673
TI  - Effect of simple motor performance on regional dopamine release in the striatum
      in Parkinson disease patients and healthy subjects: a positron emission
      tomography study.
AB  - To investigate changes in dopamine release in the striatum during motor exercise
      in human subjects with and without striatal dopamine denervation, eight healthy
      subjects and eight patients with Parkinson disease (PD) were measured during
      unilateral foot extension/flexion movement using positron emission tomography
      with [11C]raclopride. Five subjects in each group were later scanned in the
      resting condition. Estimation of binding potential (k3/k4) of [11C]raclopride was
      based on Logan plot method. Significant reductions in [11C]raclopride k3/k4 were
      found in the dorsal putamen contralateral to the exercise side in the healthy
      group and ipsilaterally in the PD group. Spearman rank correlation analysis
      showed that [11C]raclopride k3/k4 correlated inversely with the decrease in
      performance (velocity and motion range) in the dorsal putamen contralaterally in
      the healthy group and ipsilaterally in the PD group. These results suggest that
      simple but laborious motor exercise (motor stimulation) generates significant
      dopamine release in the dorsal striatum contralateral to the motor execution in
      humans. Lack of the crossed pattern and ipsilateral increase in dopamine release
      in the dorsal striatum during the unilateral limb movement may reflect the
      pathophysiology for hypokinetic and insufficient coordinating movement in PD.

PMID- 12045674
TI  - Modeling [18 F]MPPF positron emission tomography kinetics for the determination
      of 5-hydroxytryptamine(1A) receptor concentration with multiinjection.
AB  - The selectivity of [18F]MPPF (fluorine-18-labeled 4-(2;-methoxyphenyl)-1-[2;-(N
      2"-pirydynyl)-p-fluorobenzamido]ethylpiperazine) for serotonergic 5
      hydroxytryptamine(1A) (5-HT1A) receptors has been established in animals and
      humans. The authors quantified the parameters of ligand-receptor exchanges using
      a double-injection protocol. After injection of a tracer and a coinjection dose
      of [18F]MPPF, dynamic positron emission tomography (PET) data were acquired
      during a 160-minute session in five healthy males. These PET and magnetic
      resonance imaging data were coregistered for anatomical identification. A three
      compartment model was used to determine six parameters: Fv (vascular fraction),
      K1, k2 (plasma/free compartment exchange rate), koff, kon/Vr (association and
      dissociation rate), Bmax (receptor concentration), and to deduce Kd (apparent
      equilibrium dissociation rate). The model was fitted with regional PET kinetics
      and arterial input function corrected for metabolites. Analytical distribution
      volume and binding potential were compared with indices generated by Logan-Patlak
      graphical analysis. The 5HT1A specificity for MPPF was evidenced. A Bmax of 2.9
      pmol/mL and a Kd of 2.8 nmol/L were found in hippocampal regions, Kd and
      distribution volume in the free compartment were regionally stable, and the Logan
      binding potential was linearly correlated to Bmax. This study confirms the value
      of MPPF in the investigation of normal and pathologic systems involving the
      limbic network and 5-HT1A receptors. Standard values can be used for the
      simulation of simplified protocols.

PMID- 12045675
TI  - CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally
      transmissible subtype-C, CCR5-tropic Simian/Human Immunodeficiency Virus (SHIV).
AB  - An R5-tropic SHIV(CHN19P4) was previously generated using a primary HIV-1 subtype
      C envelope. We have further characterized this SHIV in two species of macaques.
      To determine whether this isolate is transmissible vaginally, female pig-tailed
      macaques were inoculated with 2 x 10(3) TCID50 of SHIV(CHN19P4) by the vaginal
      route. Animals became infected with a high peak plasma viremia (>10(7) viral
      copies/mL) and rapid seroconversion. The viremia was accompanied by CD4+
      lymphocytopenia in the gut lamina propria lymphocyte (LPL) population. Comparable
      CD4+ T-cell loss was not seen in peripheral blood and colonic lymph nodes. These
      findings demonstrate a unique R5-tropic SHIV that can be used to study envelope
      related issues in vaginal transmission of the most prevalent subtype of HIV-1. We
      also found that rhesus macaques intravenously inoculated with 1 x 10(3) TCID50 of
      SHIV(CHN19P4) became infected and showed CD4+ lymphocytopenia in the gut LPL
      population. Despite inactivation of the vpu gene in SHIV(CHN19P4), the virus
      appears to target mainly gut-associated lymphoid tissues during the initial stage
      of infection as has been described for SHIV(SF162P), another R5-tropic (subtype
      B) recombinant virus. Our data indicate that the R5-mediated CD4+ lymphocytopenia
      in the gut is likely independent of HIV-1 genotypes and of the function of vpu at
      the acute phase of viral infection.

PMID- 12045676
TI  - Increased HLA-DR expression on peripheral blood monocytes in subsets of subjects
      with primary HIV infection is associated with elevated CD4 T-cell apoptosis and
      CD4 T-cell depletion.
AB  - Whereas T-cell activation parameters of HIV disease have been extensively
      studied, the activation status of circulating monocytes has received less
      attention. Sixty-one subjects with primary HIV infection were evaluated by
      fluorescent-activated cell sorter (FACS) analysis at baseline (pretreatment) for
      CD4 T-cell count, CD4 T-cell apoptosis, and immune activation. A subset of 15
      subjects with marked elevated (3 standard deviations above normal) monocyte DR
      expression had significantly reduced CD4 T-cell counts at baseline (p <.01) when
      compared with 46 subjects without monocyte activation. Ten subjects who presented
      with elevated levels of both CD14/DR, and CD4/CD38, had higher CD4 T-cell
      apoptosis (p <.001), and lower CD4 T-cell counts (p <.001) and higher baseline
      plasma HIV RNA (p <.01) than 21 subjects without elevated CD14/DR and CD4/CD38
      coexpression. Fifty subjects were subsequently evaluated for immune cell
      activation over 24 weeks postinitiation of highly active antiretroviral therapy
      (HAART). A subgroup of 5 subjects who had persistent CD14/DR activation showed
      continuous depression of CD4 T-cell counts persisting for up to 2 years. The CD4
      T-cell counts of this subgroup were significantly lower, at all time points, in
      comparison to 35 subjects who lacked any persistent expression of monocyte or CD4
      T-cell activation (at 24 weeks, p <.002). We conclude that monocyte activation as
      defined by elevation of CD14/DR expression correlates to CD4 T-cell depletion in
      primary HIV infection, and is predictive of a poor CD4 T-cell response to HAART
      in a subset of patients.

PMID- 12045677
TI  - Predictive value of HIV-1 viral load on risk for opportunistic infection.
AB  - OBJECTIVE: The relationship between HIV-1 viral load and the risk for
      opportunistic infection (OI) was examined in Adult AIDS Clinical Trial Group
      (AACTG) 722, a virology substudy of AACTG 323: a phase 4 randomized study
      designed to examine the use of chronic suppressive versus episodic fluconazole
      therapy. METHODS: The primary analysis used a case-control sampling scheme with
      two controls per "case" (subjects that developed an OI) matched by gender, age,
      and time on study. Forty-five cases and matched controls were identified and used
      in the analysis. RESULTS: Study 722 accrued 518 subjects between 5/97 and 11/99.
      Forty-five subjects developed serious OIs or refractory candidiasis. Median
      baseline CD4 count was 24 cell/mm3 for cases and 46 for controls (p =.003).
      Median viral load (VL) was 5.02 log10 copies/mL for cases and 4.08 for controls
      (p =.002). Multivariate analysis found four independent variables associated with
      time to OI: baseline VL and CD4 (RR = 2.2 per log increment and 6.0 per 50-cell
      increment, respectively), a one log increase in VL at any time (RR = 15), and
      history of an OI (RR = 5.2). CONCLUSIONS: VL and changes in VL were independently
      associated with risk of development of OIs in a prospective study and should be
      considered by clinicians when assessing patients for risk of OI.

PMID- 12045678
TI  - "Discordant" increases in CD4 cell count relative to plasma viral load in a
      closely followed cohort of patients initiating antiretroviral therapy.
AB  - BACKGROUND: In HIV-positive persons receiving antiretroviral therapy, CD4 cell
      responses are associated with optimal suppression of viral replication. However,
      increases in CD4 cell counts in the absence of viral suppression have been
      reported. We characterized plasma viral load (pVL) and CD4 cell count increases
      in closely followed patients to evaluate determinants and the prevalence of CD4
      cell responses at a populational level. METHODS: All HIV-positive patients in the
      province of British Columbia, Canada, who were antiretroviral naive and initiated
      therapy between August 1996 and May 1998 were eligible for the study. The
      selection criteria were that patients had to have CD4 cell counts and pVLs
      measured at baseline and at least once during eight 16-week periods after the
      initiation of therapy. We characterized CD4 cell responses and sought patients
      who had a "discordant" increase at 1 year, which was defined as an increase in
      CD4 cell count of >or=50/mm3 with a <1 log10 decrease in pVL. We also evaluated
      adherence and antiretroviral use. RESULTS: Overall, when baseline and 1-year pVLs
      and CD4 cell counts were compared, 6.2% of patients had CD4 cell count increases
      without pVL decreases of >or=1 log10. However, when all pVLs before 1 year were
      considered, 92% of the discordant increases could be attributed to prior
      transient or partial viral suppression. Furthermore, although substantial
      increases in CD4 cell counts were observed in transient virologic responders, the
      cumulative number of antiretroviral agents used by this group was significantly
      higher than that used by full virologic responders (p <.001). CONCLUSIONS: Our
      results demonstrate that virtually all CD4 cell count increases can be attributed
      to transient or partial pVL suppression. Unmeasured pVL suppression likely
      explains discordant responses that have been previously reported. Similarities
      between transient and full virologic responders also appear to be time limited
      and are often associated with greater cumulative use of antiretroviral therapy by
      transient virologic responders.

PMID- 12045679
TI  - Viral replication under combination antiretroviral therapy: a comparison of four
      different regimens.
AB  - A mathematical model of the interaction among CD4+ T-cells, HIV-1, and
      antiretroviral drugs was fitted to the viral load decline following initiation of
      combination therapy to estimate differences in the residual reproductive capacity
      of virus (R(0)) in the average patient in each group. Four regimens were studied:
      12 patients on 5-drug nucleoside reverse transcriptase inhibitor (NRTIs),
      nonnucleoside reverse transcriptase inhibitor (NNRTIs) and protease inhibitor
      (PI)-containing combination therapy, 11 patients on PI-containing triple therapy,
      10 patients on double NRTI therapy, and 10 patients on NNRTI-containing triple
      therapy. Model fits were used to estimate R(0). The NNRTI-containing triple
      therapy and the 5-drug regimen blocked viral replication to the greatest extent
      (R(0) = 0.85; 95% confidence interval [CI], 0.79-0.91; and 0.90, 95% CI, 0.82
      0.98, respectively), with the former being significantly better than the PI
      containing triple regimen (R(0) = 0.98; 95% CI, 0.92-1.03; p =.007). Both the
      NNRTI-containing and the 5-drug regimen, as well as the PI-containing triple
      therapy, were significantly better at blocking viral replication than the double
      NRTI therapy (R(0) = 1.04; 95% CI, 1.0-1.07). Measurement of viral load after
      approximately 7 days provided the most accurate measure of the degree of viral
      suppression induced by a given drug regimen.

PMID- 12045680
TI  - Changing sexual behavior among gay male repeat testers for HIV: a randomized,
      controlled trial of a single-session intervention.
AB  - CONTEXT: High-risk sexual behavior is increasingly prevalent among men who have
      sex with men (MSM) and among men with a history of repeat testing for HIV.
      OBJECTIVES: The study assessed whether one counseling intervention session
      focusing on self-justifications (thoughts, attitudes, or beliefs that allow the
      participant to engage in high-risk sexual behaviors) at most recent unprotected
      anal intercourse (UAI) is effective in reducing future high-risk behaviors among
      HIV-negative men. DESIGN, SETTING, AND PARTICIPANTS: A randomized, controlled,
      counseling intervention trial was conducted at an anonymous testing site in San
      Francisco, California, between May 1997 and January 2000. Participants were 248
      MSM with a history of at least one previous negative HIV test result and self
      reported UAI (receptive or insertive) in the previous 12 months with partners of
      unknown or discordant HIV status. Two intervention groups received standard HIV
      test counseling plus a cognitive-behavioral intervention, and two control groups
      received only standard HIV test counseling. Follow-up evaluation was at 6 and 12
      months. MAIN OUTCOME MEASURE: Number of episodes of UAI with nonprimary partners
      (of unknown or discordant HIV status) in the 90 days preceding the interview was
      measured via self-report during face-to-face interview. RESULTS: A novel
      counseling intervention focusing on self-justifications significantly decreased
      the proportion of participants reporting UAI with nonprimary partners of unknown
      or discordant HIV status at 6 and 12 months (from 66% to 21% at 6 months and to
      26% at 12 months, p =.002; p <.001) as compared with a control group when added
      to standard client-centered HIV counseling and testing. CONCLUSIONS: A specific,
      single-session counseling intervention focusing on a reevaluation of a person's
      self-justifications operant during a recent occasion of high-risk behavior may
      prove useful in decreasing individual risk behavior and thus limiting community
      level HIV transmission.

PMID- 12045681
TI  - Sexual dysfunction in 156 ambulatory HIV-infected men receiving highly active
      antiretroviral therapy combinations with and without protease inhibitors.
AB  - We conducted a cross-sectional study of 156 ambulatory HIV-infected homosexual or
      bisexual men to assess and compare the prevalence and characteristics of sexual
      dysfunction according to treatment combinations (group A, protease inhibitor [PI]
      treatment; group B, no PI treatment; and C, PI treatment interrupted >1 month
      previously). The study was based on a self-administered 163-item questionnaire
      that included a French translation of the International Index of Erectile
      Function, five sections of the Derogatis Sexual Functioning Inventory, and open
      questions. Data analysis was performed using Mann-Whitney and Kruskal-Wallis H
      nonparametric tests (quantitative values) and chi2 tests (qualitative values)
      using SPSS software (SPSS, Chicago, IL, U.S.A.). One hundred fifty-six patients
      completed the study. The median age +/- SD of the patients was 40.5 +/- 7.7
      years, and the median CD4+ cell count +/- SD was 415 +/- 236/mm3. One hundred
      eleven (71%) of 156 patients reported some degree of sexual dysfunction since the
      beginning of their treatment (65 [71%] of 91 group A patients; 15 [65%] of 23
      group B patients; and 31 [74%] of 42 group C patients), with no significant
      difference among the groups. Of the 111 patients, 99 (89%) reported decrease or
      loss of libido, 76 (68%) reported orgasmic perturbation, 96 (86%) reported
      erectile dysfunction, and 65 (59%) reported ejaculation perturbation, with no
      significant difference among the three groups. There were no significant
      differences among the three groups regarding the International Index of Erectile
      Function and Derogatis Sexual Functioning Inventory scores. These data suggest
      that PI-based therapy does not seem to increase sexual dysfunction in this
      patient population.

PMID- 12045682
TI  - Electron beam computed tomography for assessment of coronary artery disease in
      HIV-infected men receiving antiretroviral therapy.
AB  - Hyperlipidemia has been seen in patients receiving protease inhibitor-based
      antiretroviral therapy, prompting concern that such patients are at risk for
      accelerated coronary artery disease (CAD). To assess the risk of CAD in
      antiretroviral-treated HIV-infected men, we quantified coronary artery calcium
      (CAC), a sensitive and established marker of subclinical CAD, using electron beam
      computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met
      the following criteria (cases) were enrolled in the study: age of 40 years or
      older; naive to antiretroviral therapy or use of a stable antiretroviral regimen
      for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease
      inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT
      derived CAC scores, serum lipid levels, history of antiretroviral therapy, and
      risk factors for CAD were obtained. Each case was compared with three age-, sex-,
      and race-matched HIV-negative controls randomly selected from a database
      including >9000 patients who had undergone EBCT. We determined differences in the
      proportion of cases and controls with CAC scores of >0 (detectable calcium) and
      clinically significant CAC for age range. There were no statistically significant
      differences between the number of cases and controls with detectable CAC (33% and
      39%, respectively) and clinically significant CAC (18% and 17%, respectively).
      This study suggests that the rate of coronary atherosclerosis among HIV-infected
      patients who receive short-term antiretroviral therapy with or without protease
      inhibitors is not higher than that among age-, sex-, and race-matched HIV
      negative controls. These results need to be confirmed in larger long-term
      studies, with controls well matched for coronary risk factors.

PMID- 12045683
TI  - Prevention of mother-to-child HIV transmission in the context of a comprehensive
      AIDS agenda in resource-poor countries.

PMID- 12045684
TI  - Safety of antiretroviral prophylaxis of perinatal transmission for HIV-infected
      pregnant women and their infants.
AB  - Worldwide, more than 1600 infants become infected with HIV each day. Almost all
      infections are a result of mother-to-child transmission of HIV, with most of
      these infections occurring in resource-poor countries. In developed countries,
      antiretroviral prophylaxis has dramatically reduced perinatal transmission to
      <2%. The potential now exists to extend this success to resource-poor countries
      using effective but shorter and less expensive antiretroviral regimens. With the
      potential widespread use of antiretroviral therapy for perinatal HIV prevention
      in resource-limited settings, there will be exposure of increasing numbers of
      infants to in utero and postpartum antiretroviral drugs for which long-term
      toxicity data is unknown. This article focuses on a review of what is known about
      safety of antiretroviral regimens used to interrupt mother-to-child transmission
      for women and their children.

PMID- 12045685
TI  - Antiretroviral prophylaxis of perinatal HIV-1 transmission and the potential
      impact of antiretroviral resistance.
AB  - Since 1994, trials of zidovudine, zidovudine and lamivudine, and nevirapine have
      demonstrated that these antiretroviral drugs can substantially reduce the risk of
      perinatal HIV-1 transmission. With reductions in drug price, identification of
      simple, effective antiretroviral regimens to prevent perinatal HIV-1
      transmission, and an increasing international commitment to support health care
      infrastructure, antiretrovirals for both perinatal HIV-1 prevention and HIV-1
      treatment will likely become more widely available to HIV-1-infected persons in
      resource-limited countries. In the United States, widespread antiretroviral usage
      has been associated with increased antiretroviral drug resistance. This raises
      concern that drug resistance may reduce the effectiveness of perinatal
      antiretroviral prophylaxis as well as therapeutic intervention strategies. The
      purpose of this article is to review what is known about resistance and risk of
      perinatal HIV transmission, assess the interaction between antiretroviral
      resistance and the prevention of perinatal HIV-1 transmission, and discuss
      implications for current global prevention and treatment strategies.

PMID- 12045686
TI  - Breast-feeding and HIV-1 transmission in resource-limited settings.
AB  - In many international settings, transmission of the HIV virus during lactation
      accounts for one third to one half of all HIV transmission from mothers to
      infants. Reduction of HIV transmission during lactation is one of the most
      pressing public health dilemmas confronting perinatal researchers, health policy
      makers, and HIV-infected women in many areas of the world. While results of
      clinical trials, laboratory and observational studies have increased our
      understanding of risk factors for breast-feeding transmission and the timing of
      postnatal transmission, there are no proven strategies known to reduce the risk
      of HIV transmission during breast-feeding for those HIV-infected women who opt to
      breast-feed in developing countries. Approaches to decreasing transmission of HIV
      through breast-feeding that will be studied include trials of combination
      antiretrovirals given to mothers during lactation. These research efforts using
      maternal antiretrovirals for perinatal HIV prevention during breast-feeding will
      interface with emerging plans for treatment programs in developing countries.

PMID- 12045687
TI  - Higher viral loads and other risk factors associated with HIV-1 seroconversion
      during a period of high incidence among injection drug users in Bangkok.
AB  - We analyzed data from a prospective cohort study of injection drug users (IDUs)
      attending methadone treatment clinics in Bangkok, Thailand, during 1995-1998 to
      characterize factors associated with a period of high incidence (PHI) from July
      1996 through January 1997 compared with periods of lower incidence.
      Sociobehavioral characteristics were similar for all participants during and
      outside the PHI except for the following: there was more reported drug injection
      while IDUs were incarcerated during the PHI (odds ratio, 1.67; p =.02) and
      significantly higher proportions of persons reported heroin injection (91% vs.
      75%, respectively; p =.02) and higher frequencies of daily injection and sharing
      of injection equipment (40% vs. 25%, respectively; p =.05) during the PHI than
      outside the PHI. Through most of the first year after seroconversion, plasma HIV
      1 loads were significantly higher in persons who seroconverted during the PHI
      than in those who seroconverted outside the PHI. Higher viral loads may
      potentially contribute to faster disease progression and increased infectiousness
      or transmissibility to subsequent contacts. Our findings suggest that prevention
      efforts to reduce the effective size and turnover within IDU sharing networks may
      have a significant impact on the epidemic by disrupting the rapid transmission of
      HIV-1 from recently infected, highly infectious individuals.

PMID- 12045688
TI  - Genetic analysis of incident HIV-1 strains among injection drug users in Bangkok:
      evidence for multiple transmission clusters during a period of high incidence.
AB  - During 1995-1996, 1,209 HIV-1-negative injection drug users (IDUs) attending
      methadone treatment clinics operated by the Bangkok Metropolitan Administration
      in Bangkok, Thailand, were enrolled in a prospective cohort study. Through 1998,
      133 of these IDUs had seroconverted to HIV-1; 130 of these seroconverters were
      included in this study. HIV-1 CRF01_AE and subtype B strains accounted for 79%
      and 21% of the incident infections, respectively. To examine phylogenetic
      relationships among these incident HIV-1 strains, we used several phylogenetic
      inference methodologies to analyze the env (C2-V4) sequences in blood samples
      collected soon after seroconversion. These analyses consistently revealed eight
      phylogenetic clusters comprising 21 incident strains (bootstrap method, >80%; six
      CRF01_AE and two subtype B clusters). Two factors were found to be associated
      with the eight clusters. The first factor was temporal: seven of the eight
      clusters comprised 17 sequences from IDUs whose estimated dates of seroconversion
      were within a period of high incidence from July 1996 through January 1997. The
      second factor was a possible geographic association: four clusters were observed
      among IDUs who had attended the same methadone treatment clinics. These
      phylogenetic clusters likely represent subgroups within larger HIV transmission
      networks among IDUs in Bangkok. Despite prevention efforts, the incidence of HIV
      1 infection among the Bangkok IDU population continues to be high. A better
      understanding of transmission networks and factors associated with such networks
      can help guide prevention efforts.

PMID- 12045689
TI  - Response of AIDS-associated Kaposi sarcoma to highly active antiretroviral
      therapy alone.

PMID- 12045690
TI  - HIV genotype mutations evoked by nelfinavir-based regimens: frequency,
      background, and consequences on subsequent treatment options.

PMID- 12045691
TI  - Limited impact of highly active antiretroviral therapy in thrombocytopenia.

PMID- 12045693
TI  - Thoughts on celebrating nursing.

PMID- 12045692
TI  - Monitoring HIV viral loads in the United States: recent trends and methodologies.

PMID- 12045694
TI  - Remembering Florence Nightingale.

PMID- 12045695
TI  - Telenurses today: creating the new picture of home care.

PMID- 12045696
TI  - Contracted hospice services: the Joint Commission pharmaceutical services and
      home medical equipment survey process.

PMID- 12045697
TI  - Misconceptions of older adults with hypertension concerning OTC medications and
      alcohol.
AB  - Knowledge and self-efficacy concerning interactions of antihypertensives with
      over-the-counter (OTC) analgesics and alcohol were assessed in 51 adults aged 60
      and older taking antihypertensives and attending a blood pressure clinic. The
      subjects had low self-efficacy about how to prevent interactions of
      antihypertensives with OTC analgesics and alcohol. Inspection of knowledge item
      responses revealed eight general misconceptions about OTC medications. These data
      guide educating those with hypertension about potential drug interactions arising
      from self-medication.

PMID- 12045698
TI  - Have you mastered PPS?

PMID- 12045701
TI  - Nutrition and diet training for home care aides.

PMID- 12045699
TI  - What every nurse should know about mercury.
AB  - Mercury is found in many of the devices used by healthcare professionals,
      including thermometers and sphygmomanometers. The growing awareness about
      exposure to mercury demands home care nurses understand the basics to teach
      patients and families about the dangers. This article outlines core concerns and
      provides specific information and resources about mercury.

PMID- 12045702
TI  - The blessings and burdens of interdisciplinary teamwork.

PMID- 12045703
TI  - Pain management resources.

PMID- 12045708
TI  - A T-cell receptor gamma polymerase chain reaction assay using capillary
      electrophoresis for the diagnosis of cutaneous T-cell lymphomas.
AB  - Detection of clonal T-cell receptor gamma rearrangements by polymerase chain
      reaction (TCRgamma PCR) followed by high-resolution electrophoresis has now
      become a valuable tool in the diagnosis of cutaneous T-cell lymphoma (CTCL). The
      identification of clonal TCRgamma PCR products by fluorescent fragment analysis
      (FFA) on a capillary DNA sequencer is described here and compared with an
      established hetero-duplex temperature gradient gel electrophoresis (HD-TGGE). Of
      55 CTCL derived lesional skin samples, clonality was obtained in 46 samples by
      FFA (83.6%) and in 45 samples by HD-TGGE (81.8%). Of 35 control skin specimens
      from various nonmalignant dermatoses, two samples (pityriasis lichenoides
      chronica) showed clonality by both methods, one sample (chronic dermatitis) only
      by FFA. The sensitivity of FFA was established using three clonal T-cell lines
      and peripheral blood mononuclear cells. The detection limit for clonal material
      was approximately 1% to 2.5% in mixtures of DNA and 1% to 3% in cell dilutions.
      For cell dilution series, we confirmed a linear correlation between the
      clonal/polyclonal peak-size ratios and the portion of clonal cells up to about
      10%. Thus, the initial ratio between mono-and polyclonal template is correctly
      displayed by FFA within that concentration range. In conclusion, FFA on capillary
      DNA sequencer is a well-suited separation technique in TCRgamma PCR-based
      clonality analysis also exhibiting quantitative properties.

PMID- 12045709
TI  - Semireannealing, single-stranded conformational polymorphism: a novel and
      effective tool for the diagnosis of T-cell clonality.
AB  - Single-stranded conformational polymorphism (SSCP) is often used for the
      diagnosis of T-cell clonality in lymphoproliferative disorders. We introduce a
      semireannealing SSCP (SR-SSCP) protocol that is rapid, reproducible, and
      effective. By denaturing and reannealing the polymerase chain reaction (PCR)
      product before high-resolution polyacrylamide gel electrophoresis, it is possible
      to generate a diagnostic fingerprint for each case with clonal T-cell receptor
      gamma (TCR-gamma) gene rearrangement detected after PCR with TCR-gamma specific
      consensus primers. Discrete and distinct denatured single-stranded DNA band
      profiles characterize the rearranged TCR-gamma clones. In the same gel, the clone
      size may be estimated in the reannealed double-stranded PCR DNA and can be
      assessed down to the 2% clonal T-cell population level. Eighty-four cases,
      including 37 T-cell neoplasms, 29 B-cell neoplasms, and 18 reactive lymph node
      samples were analyzed by SR-SSCP. Clonal TCR-gamma rearrangement was diagnosed in
      32 out of 37 T-cell neoplasms but in none of the B-cell tumors or reactive lymph
      node samples corresponding to sensitivity and specificity of 86.5% and 100%,
      respectively. We compare the results of SR-SSCP to those obtained by capillary
      electrophoresis and direct sequence analysis with 100% correlation. This novel
      method is applicable to any system for identification and quantitation of
      microheterogeneity in PCR products.

PMID- 12045710
TI  - Diffuse large B-cell lymphoma of the stomach: assessment of microsatellite
      instability, allelic imbalance, and trisomy of chromosomes 3, 12, and 18.
AB  - Several types of genetic aberrations including microsatellite instability (MSI),
      allelic imbalance (AI), and chromosomal trisomies have been reported in low-grade
      (LG) mucosa-associated lymphoid tissue (MALT)-type gastric lymphomas. Presence of
      such genetic alterations could be a discriminator between de novo large cell
      lymphoma and high-grade (HG) MALT-type lymphoma. We investigated 17 primary
      gastric large B-cell lymphomas with and without features of MALT-type lymphoma
      for MSI, AI, and presence of trisomy of chromosomes 3, 12, and 18. We studied
      resection specimens from 17 primary gastric extranodal diffuse large B-cell
      lymphomas. Cases classified as HG MALT-type lymphoma, based on either the
      presence of LG MALT-type lymphoma component in the background (L/H MALT) or large
      cell lymphoepithelial lesions (HG MALT), and diffuse large B-cell lymphoma (DLBCL
      NOS) when no features of MALT were present. MSI was analyzed using fluorescently
      labeled polymerase chain reaction primers (D3S11, D6S262, D3S1261, D3S1262,
      D3S1265). Paired tumor and normal DNA samples were amplified, and PCR products
      were analyzed on a DNA sequencer (ABI PRISM 373XL) with GeneScan (Applied
      Biosystems, Foster City, CA). MSI was defined as a gain of a novel-length allele
      compared with the corresponding normal tissue. AI was assessed at locus 3q27
      (D3S1262 and D3S1265). The cases were analyzed for the presence of trisomy of
      chromosomes 3, 12, and 18 using interphase fluorescence in situ hybridization.
      MSI was detected in 4 out of 15 (27%) cases from which DNA was amplifiable with
      all primers and all MALT-type lymphomas. In two cases (13%), MSI was present at
      two loci sufficient to be classified as high-frequency MSI (MSI-H); this was seen
      exclusively in HG MALT lymphomas (P = 0.04). In the remaining two cases, MSI was
      detected at a single locus (low-frequency MSI). Allelic imbalance at the locus
      D3S1262 was detected in 4 out of 17 (24%) cases. It occurred more commonly in
      stage IE lymphomas when compared with higher stages (P = 0.03), regardless of
      lymphoma subtype. Trisomy 12 was detected in 3 out of 17 cases (18%) exclusively
      in stage IE lymphomas (P = 0.08). MSI was uncommon and was found exclusively in
      MALT-type lymphomas. MSI-H was even less common but occurred in HG MALT lymphomas
      only. Allelic imbalance at 3q27 (D3S1262) and trisomy 12 were found more commonly
      in low-stage disease. The latter two findings are in concordance with the recent
      suggestion that the published variation in gain of chromosomal material in high
      grade gastric lymphomas may be related to stage rather than to the subtype of
      lymphoma. Because of the relatively low frequency of MSI in the high-grade B-cell
      lymphomas of the stomach, this feature cannot be used to reliably discriminate
      between the histologic types of extranodal diffuse large B-cell lymphoma.

PMID- 12045711
TI  - Epstein-Barr virus-positive Hodgkin/Reed-Sternberg-like B cell in non-hodgkin
      lymphoma: nucleotide sequence of the amplified immunoglobulin heavy-chain
      variable region gene by the single-cell polymerase chain reaction technique.
AB  - We examined nucleotide sequences of Epstein-Barr virus (EBV)-positive
      Hodgkin/Reed-Sternberg (HRS)-like B cells in a case of diffuse large B-cell
      lymphoma (DLBCL) and a case of adult T-cell lymphoma (ATL) for single-cell
      polymerase chain reaction of the immunoglobulin heavy-chain gene variable region
      (VH gene). HRS-like B cells were scattered in the area irrelevant to the lymphoma
      infiltrates of DLBCL and in the lymphoma area of ATL. HRS-like B cells were
      positive for CD20 and CD30 but negative for CD15. EBV presented in HRS-like B
      cells in both cases but not in any lymphoma cells. VH genes of five HRS-like B
      cells analyzed in DLBCL were polyclonal and showed in-frame sequences with 0% to
      2.8% somatic mutation frequency. In an ATL, VH genes of five HRS-like B cells
      analyzed were polyclonal and somatically mutated. Four cells carried in-frame
      rearrangements with 3.5% to 17.7% mutation frequency. One of the VH genes has a
      one-codon deletion. From the fifth cell, an out-of-frame rearrangement with an
      insertion and a deletion was obtained. Thus, we showed polyclonal EBV-positive
      HRS-like B cells in both DLBCL and ATL and that whereas EBV-positive, HRS-like B
      cells in DLBCL exhibited unmutated and mutated VH gene, those in ATL were found
      to have a somatically mutated VH gene with/without deletions and/or insertions.
      The HRS-like B cells may appear because of active EBV infection in a patient who
      is immunosuppressed from the primary lymphoma.

PMID- 12045712
TI  - Effect of blood sample handling and reverse transcriptase-polymerase chain
      reaction assay sensitivity on detection of CK20 expression in healthy donor
      blood.
AB  - Data concerning the specificity of cytokeratin 20 (CK20) as a reverse
      transcriptase-polymerase chain reaction analysis (RT-PCR) marker to detect
      disseminated tumor cells in blood are conflicting. Underlying causes for these
      discrepancies need to be determined to clarify the significance of CK20
      detection. Because differences in RT-PCR assays and blood sample handling may be
      important, their influence on CK20 detection was studied. Using a series of
      healthy donor blood samples spiked with colon tumor cells, the authors compared
      the sensitivities of two conventional PCRs with different primer sets and a
      quantitative LightCycler PCR (Roche Diagnostics GmbH, Penzberg, Germany).
      Additionally, the influence of sample collection and preparation on assay
      specificity was studied by examining CK20 expression in the mononuclear cell
      fraction (MNC) of the first and the second aliquot of blood drawn from healthy
      donors and in the granulocyte cell fraction. At the concentration of one spiked
      tumor cell/mL blood, the CK20 detection frequency varied from 17% and 67% for the
      conventional to 78% for the LightCycler PCR. In the unspiked samples, CK20 was
      detected in 0% and 8% of the conventional and in 11% of the LightCycler PCR
      tests. Quantitative analysis revealed that CK20 was expressed at a high level in
      the granulocyte samples. The results demonstrate that differences in assay
      sensitivity and sample handling influence CK20 detection in blood.

PMID- 12045714
TI  - Length analysis of polymerase chain reaction products: a sensitive and reliable
      technique for the detection of mutations in KIT exon 11 in gastrointestinal
      stromal tumors.
AB  - Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the
      digestive tract. These tumors express the c-kit receptor tyrosine kinase, and
      many have activating mutations in the juxtamembrane region coded by the exon 11
      of KIT. Detection of these mutations has prognostic and therapeutic impact. The
      aim of the study was to compare a new detection method by length analysis of
      polymerase chain reaction products (LAPP) to direct sequencing. The detection of
      either deletion or insertion mutations within the exon 11 of KIT was performed on
      genomic DNA extracted from 40 paraffin-embedded samples from 38 patients. Double
      strand direct sequencing revealed a mutation in 25 of 40 samples. In two
      additional samples, a mutation was suspected but could not be determined by
      sequencing. LAPP revealed a mutation in 27 samples, corresponding to the 25
      determined and 2 suspected samples. One of these latter samples contained three
      different alleles. Mutations corresponded to either deletions (n = 24) or
      insertion (n = 1) and had the same size with sequencing and LAPP. Our results
      show that LAPP is as accurate and more sensitive than direct sequencing for the
      detection of deletion or insertion mutations of exon 11 of KIT in
      gastrointestinal stromal tumors.

PMID- 12045713
TI  - Detection procedures for neuroblastoma cells metastatic to blood and bone marrow:
      blinded comparison of chromogranin A heminested reverse transcription polymerase
      chain reaction to tyrosine hydroxylase nested reverse transcription polymerase
      chain reaction and to anti-GD2 immunocytology.
AB  - Specific and sensitive tumor cell detection is becoming increasingly important
      for diagnosing and staging as well as for the therapeutic management of
      neuroblastoma patients. We propose a chromogranin A heminested reverse
      transcription polymerase chain reaction (CgA hn RT-PCR) procedure for the
      detection of neuroblastoma minimal residual disease in peripheral blood and bone
      marrow samples. The results were checked in comparison with the presently
      available procedures (i.e., with the tyrosine hydroxylase nested RT-PCR [TH n RT
      PCR] and with the immunocytochemical approach using anti-GD2 antibodies).
      Controls from healthy patients or from people with unrelated disease (12 samples
      of bone marrow and 23 samples of peripheral blood) and serial dilution
      experiments using neuroblastoma cell lines (SKNLP, SKNFI, STA6, STA8) showed CgA
      hn RT-PCR full specificity and sensitivity ranging from 10(3) to 10(6) (depending
      on the cell line). The results compared favorably with those obtained using TH n
      RT-PCR. Preliminary data obtained analyzing bone marrow and peripheral blood
      specimens from stage IV neuroblastomas showed substantially overlapping results
      between CgA and TH n RT-PCR procedures. Our data support the potential usefulness
      of CgA heminested RT-PCR as a specific and sensitive procedure for minimal
      disease detection in neuroblastoma. A prospective evaluation of this tool in
      clinical studies might be warranted.

PMID- 12045715
TI  - Androgen and estrogen receptor mRNA status in apocrine carcinomas.
AB  - Eleven pure apocrine carcinomas (8 breast, 2 vulvar, 1 axillary) were evaluated
      for the presence of androgen and estrogen receptor mRNA. These
      immunohistochemically androgen receptor positive and estrogen receptor negative
      cases were microdissected and analyzed by the reverse transcription polymerase
      chain reaction for the presence of receptor message. Nine of these 11 estrogen
      receptor (ER) negative lesions were found to contain the ER mRNA through the
      first intron splice region. In 4 of the 11 cases, the androgen receptor (AR) mRNA
      could not be shown even though the protein was detected immunohistochemically. In
      the other seven, AR mRNA was identified. This indicates that the mechanism for
      production of the estrogen receptor is intact and functional in most cases
      through the first transcriptional splice region. Therefore, the
      immunohistochemical absence of the estrogen receptor in apocrine cells cannot be
      explained by an abnormal message at these common sites and should be sought
      beyond these points.

PMID- 12045716
TI  - In situ hybridization for the identification of filamentous fungi in tissue
      section.
AB  - Identification of fungi in tissue sections can be difficult because of limited
      biopsy tissue with only a few organisms present, or mycelial elements may be the
      only forms present, rendering common organism types indistinguishable from one
      another. In situ hybridization may assist in the rapid and accurate
      identification of such fungi. In this study, DNA probes were directed against the
      5S or 18S ribosomal RNA sequences of three groups of fungi with a high degree of
      specificity for each. Two of the three, Aspergillus and Zygomycetes species, are
      usually seen in tissue purely in their hyphal forms. The third, Candida species
      is seen less commonly as predominantly mycelial elements. Probes were tested on
      61 formalin-fixed, paraffin-embedded tissue specimens, each with culture-proven
      involvement by one of these organisms (Candida species, n = 21; Aspergillus
      species, n = 27; Zygomycetes, n = 13). Accuracy of both in situ hybridization
      (ISH) and morphology, based on the examination of Grocott methanamine silver
      (GMS)- and periodic acid-Schiff (PAS)-stained slides, was compared with culture.
      The results showed that morphologic examination (GMS and PAS) showed a slightly
      greater sensitivity in detecting the presence of fungi (98%) compared with in
      situ hybridization (95%). DNA probes, however, were more accurate in correctly
      identifying those organisms present. Although ISH specific probes showed 97%
      positive predictive value (PPV), examination of GMS-and PAS-stained slides had an
      86% PPV when compared with culture-based identification methods. These results
      show that ISH, directed against ribosomal RNA, provides a rapid and accurate
      technique for the identification of mycelial fungal organisms in histologic
      tissue sections. Its primary use lies in the ability to accurately distinguish
      between organisms that have similar or identical morphologic features by light
      microscopy.

PMID- 12045717
TI  - Pathogenesis of multiple sclerosis: an update on immunology.
AB  - Multiple sclerosis is characterized by demyelination and chronic inflammation of
      the central nervous system. Extensive studies in the animal model experimental
      autoimmune encephalomyelitis have suggested that multiple sclerosis is an
      autoimmune disorder mediated by myelin-specific CD4 T cells secreting T helper
      type 1 cytokines and tumor necrosis factor alpha. This concept has been widely
      used to develop new experimental therapies. However, recent findings in both
      experimental autoimmune encephalomyelitis and multiple sclerosis question a
      simple CD4 T helper type 1 T cell paradigm and provide evidence for the role of
      various immune cells in the pathogenesis of experimental autoimmune
      encephalomyelitis and multiple sclerosis. In this paper we review recent progress
      and discuss the implications for new therapeutic strategies.

PMID- 12045718
TI  - Immunological indicators of disease activity and prognosis in multiple sclerosis.
AB  - The need to ensure an accurate diagnosis and proper treatment for multiple
      sclerosis patients, considering the various clinical and immunopathological
      subtypes of the disease, requires the identification of biomarkers that measure
      disease activity and predict the course of disease development in individual
      patients. Moreover, the identification of effective indicators will lead not only
      to optimized patient treatment but also to the development of better tools for
      evaluating clinical trials. Recent studies focusing on the identification of
      possible immunological markers in multiple sclerosis will be reviewed.

PMID- 12045719
TI  - The clinico-radiological paradox in multiple sclerosis revisited.
AB  - The use of magnetic resonance imaging as a surrogate outcome measure in clinical
      trials, or even as a prognosticator in the assessment of the natural evolution,
      assumes a close relationship between extent and rate of development of magnetic
      resonance imaging abnormalities with the clinical status and rate of development
      of disability. While it may seem obvious that patients who develop new lesions
      are worse off than those without new lesions, the association between clinical
      findings and radiological extent of involvement is generally poor. In this
      review, various confounders are discussed, including inappropriate clinical
      rating, lack of histopathological specificity (especially for axonal loss),
      neglect of spinal cord involvement, underestimation of damage to the normal
      appearing brain tissue (both white and gray matter), and masking effects of
      cortical adaptation. It is concluded that much progression has been made in
      magnetic resonance techniques so that the clinico-radiological dissociation has
      indeed proved to be a paradox. Thus, the relevance of normal appearing brain
      tissue damage, residual brain volume, spinal cord damage and cerebral plasticity
      had to be reiterated. The increased awareness of the subtle interplay between
      these dimensions should be kept in mind when magnetic resonance is used as a
      surrogate outcome measure. This corroborates with conventional wisdom that one
      should not rely on a single magnetic resonance measure, but take full advantage
      of the fact that magnetic resonance is able to provide multidimensional
      information.

PMID- 12045721
TI  - The diagnosis of multiple sclerosis.
AB  - Multiple sclerosis is a clinical diagnosis and as such requires the integration
      of historical information with neurological examination and relevant laboratory
      and paraclinical tools, such as magnetic resonance imaging. A recent revision of
      the diagnostic guidelines for multiple sclerosis has been published that
      formalizes the use of magnetic resonance imaging information along with the
      clinical picture. These new guidelines should provide for the earlier and easier
      diagnosis of multiple sclerosis, useful for both clinical trials and neurological
      practice.

PMID- 12045720
TI  - Magnetic resonance spectroscopy in multiple sclerosis: window into the diseased
      brain.
AB  - Magnetic resonance spectroscopy provides noninvasive insight into the regional
      and global biochemical alterations that are concomitants of the dynamic processes
      that underlie the evolution of fundamental pathologic changes in multiple
      sclerosis. These include now well-recognized alterations of neuronal biochemical
      markers that accompany tissue destruction readily visualized by magnetic
      resonance imaging, but also dynamic changes in several metabolites that indicate
      pathological processes that precede the magnetic resonance imaging-defined
      lesion, or completely escape current high-resolution imaging.

PMID- 12045722
TI  - Natural history of multiple sclerosis: implications for counselling and therapy.
AB  - Recent advances in our knowledge of the natural history of multiple sclerosis
      deal with the influence of pregnancy and vaccination, the predictive value of
      magnetic resonance imaging-based criteria in terms of activity and severity of
      the disease, and the weighting of the interplay between relapses and clinical
      progression. These advances have implications for counselling of patients and
      adjusting the classification of the disease course. Thus multiple sclerosis
      should be considered to be as much neurodegenerative as inflammatory and disease
      modifying therapeutic strategies should be reconsidered by focusing on protection
      and repair of the nervous system.

PMID- 12045723
TI  - Progress in neurorehabilitation in multiple sclerosis.
AB  - Despite being acknowledged as an important component in the overall management of
      multiple sclerosis, the relatively few evaluative studies in symptomatic
      treatment and rehabilitation have meant that the evidence base is still poor. The
      encouraging work on health outcome measures, together with an improved
      understanding of the mechanisms underlying disability, provide a useful base for
      improving the lot of patients with multiple sclerosis. These advances need to be
      associated with improved models of care which provide comprehensive and
      accessible services throughout the course of the disease.

PMID- 12045724
TI  - Sexual and urological dysfunction in multiple sclerosis: better understanding and
      improved therapies.
AB  - The fundamental strategy in treating multiple sclerosis patients with unstable
      bladders involves a combination of suppressing urgency and ensuring effective
      urinary drainage. Anti-cholinergics remain the first-line treatment, but
      alternative therapies are undergoing clinical trials. With a range of new pro
      erectile oral medications available, interest has grown in treatment of multiple
      sclerosis-related erectile failure. Female sexual dysfunction is also now gaining
      some attention, with new classification criteria and methods for assessing and
      treating these patients.

PMID- 12045725
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy.
AB  - In chronic inflammatory demyelinating polyradiculopathy differing clinical
      subtypes are beginning to emerge as has already occurred with the Guillain-Barre
      syndrome. However, neither pathogenic correlates nor particular therapeutic
      approaches have yet been defined for these subgroups. The neurophysiological
      techniques of terminal latency index and of modified F ratio help differentiate
      chronic inflammatory demyelinating polyradiculopathy from IgM paraproteinaemic
      neuropathy. Diagnosis may be assisted by magnetic resonance imaging studies in
      which enlarged nerve roots and plexuses and gadolinium enhancement may be
      evident. Further insight into pathogenesis has come from studies showing
      pathogenic antibodies in a small percentage of patients. Immunohistological
      studies examining the presence of adhesion, co-stimulatory and antigen presenting
      molecules in nerve biopsies have shown that T cell activation can be initiated
      and perpetuated within nerve and that Schwann cells possess the necessary markers
      to function as antigen presenting cells. Recent clinical trials have confirmed
      the therapeutic short term efficacy of intravenous immunoglobulin and Prednisone.

PMID- 12045726
TI  - Headache.

PMID- 12045727
TI  - Chronic daily headache: nosology and pathophysiology.
AB  - Systematic scientific classification of primary headaches is inexact, relying on
      clinical features because the disorders lack diagnostic markers, although the
      International Headache Society classification has been successful in providing
      relatively homogenous clinical groups for pathophysiological and therapeutic
      studies. One area in which there have been particular difficulties and
      uncertainty is in classifying patients with frequent headache, particularly
      chronic daily headache. Clinical research on the topic is limited, and imprecise
      because of uncertainties of definition. Rigorous basic or applied clinical
      research is a rarity, attested to by a paucity of new publications in the past
      year. Accordingly, the scientific basis of chronic daily headaches remains to be
      determined. There is agreement on one issue: for headache specialists and
      neurologists this is an important clinical problem. We take the position that
      chronic daily headache is what it says--frequent headache. As hematologists make
      a diagnosis of anemia, which invites further investigation and sub
      classification, neurologists might diagnose chronic daily headache not to imply
      that all its causes are the same but simply to begin the clinical process.

PMID- 12045728
TI  - Chronic daily headache in pediatric practice.
AB  - Improving the quality of life of the patient presenting with chronic daily
      headache proves to be challenging both diagnostically and with regard to their
      short- and long-term management. Continued progress has been made in the
      classification of chronic daily headache. The extent to which an initial
      evaluation should be conducted to obtain a diagnosis is a paramount consideration
      for both the patient and the family. The introduction of disability tools
      targeted for this population, both in use and under evaluation, will assist in
      both the initial assessment and in guiding management. The chronic daily headache
      patient in most cases requires both a non-pharmacological and a pharmacological
      approach with clearly defined short- and long-term goals. The management of the
      expectations of both the patient and family are the key to a good outcome.

PMID- 12045729
TI  - The electrophysiology of migraine.
AB  - Migraine is currently regarded as a neurovascular disorder of trigeminal sensory
      processing, generated centrally, probably at the level of the brainstem. In the
      past, electrophysiological techniques have drawn no definite conclusions on
      either interictal or ictal changes in migraineurs compared with controls, largely
      because of methodological differences. Recently, two findings have been shown
      consistently: an interictal increasing lack of habituation of evoked potentials
      with a normalization at the start of the attack and strong intensity dependence
      of auditory evoked potentials. These findings substantiate migraine sufferers as
      having an abnormal trait interictally, with the attack characterized by a change
      in the state of central processing. Exploitation of these differences may be a
      useful tool to study the mechanism of action of drugs used for the treatment of
      migraine.

PMID- 12045730
TI  - Calcium channel mutations and migraine.
AB  - An increasing number of mutations in the CACNA1A gene have been identified, which
      are associated with a broad clinical spectrum, including familial hemiplegic
      migraine. Transfection studies and mouse model analyses are currently being
      undertaken to study the correlation between CACNA1A mutations and disease.

PMID- 12045731
TI  - Integrating the triptans into clinical practice.
AB  - The triptans (selective serotonin agonists) are becoming the first-line
      alternatives in the acute pharmacological treatment of migraine, at least for
      attacks of moderate-to-severe intensity. Although clinical trials demonstrate
      significant differences in efficacy between triptan tablets, they often appear
      similar in efficacy when used in clinical practice, particularly after dose
      adjustments. Most patients with migraine consider drugs that can be administered
      orally to be the most user-friendly. However, gastrointestinal absorption may be
      impaired during migraine attacks because gastric motility is inhibited, and there
      is a risk that nausea during the attack will culminate in vomiting. Furthermore,
      in addition to their antimigraine properties, triptans may prolong the gastric
      emptying time. For this reason the absorption of any triptan taken orally during
      the migraine attack will be erratic and treatment effects inconsistent. Despite
      these barriers to good efficacy and high reliability, the tablet is the most
      commonly used triptan formulation.

PMID- 12045732
TI  - How much control does the brain exert over the immune system?

PMID- 12045733
TI  - Update on rabies.
AB  - Rabies remains an important public health problem worldwide due to endemic dog
      rabies in developing countries. Rabies was a re-emerging disease in the United
      States during the 1990s due to bat rabies virus variants. Australian bat
      lyssavirus also emerged in Australian bat populations and caused two human
      deaths. There have been important recent advances in our knowledge of the
      pathogenesis of rabies and in our ability to diagnose and prevent it.

PMID- 12045734
TI  - Neurological adverse events associated with vaccination.
AB  - Public tolerance to adverse reactions is minimal. Several reporting systems have
      been established to monitor adverse events following immunization. The present
      review summarizes data on neurologic complications following vaccination, and
      provides evidence that indicates whether they were directly associated with the
      vaccines. These complications include autism (measles vaccine), multiple
      sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis
      vaccine), Guillain-Barre syndrome and giant cell arteritis (influenza vaccine),
      and reactions after exposure to animal rabies vaccine. Seizures and
      hypotonic/hyporesponsive episodes following pertussis vaccination and potential
      risks associated with varicella vaccination, as well as vaccine-associated
      paralytic poliomyelitis following oral poliovirus vaccination, are also
      described. In addition, claims that complications are caused by adjuvants,
      preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium),
      neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine
      derived materials)] are discussed.

PMID- 12045735
TI  - Immunopathogenesis of acute transverse myelitis.
AB  - Acute transverse myelitis is a group of disorders characterized by focal
      inflammation of the spinal cord and resultant neural injury. Acute transverse
      myelitis may be an isolated entity or may occur in the context of multifocal or
      even multisystemic disease. It is clear that the pathological substrate--injury
      and dysfunction of neural cells within the spinal cord--may be caused by a
      variety of immunological mechanisms. For example, in acute transverse myelitis
      associated with systemic disease (i.e. systemic lupus erythematosus or
      sarcoidosis), a vasculitic or granulomatous process can often be identified. In
      idiopathic acute transverse myelitis, there is an intraparenchymal or
      perivascular cellular influx into the spinal cord, resulting in the breakdown of
      the blood-brain barrier and variable demyelination and neuronal injury. There are
      several critical questions that must be answered before we truly understand acute
      transverse myelitis: (1) What are the various triggers for the inflammatory
      process that induces neural injury in the spinal cord? (2) What are the cellular
      and humoral factors that induce this neural injury? and (3) Is there a way to
      modulate the inflammatory response in order to improve patient outcome? Although
      much remains to be elucidated about the causes of acute transverse myelitis,
      tantalizing clues as to the potential immunopathogenic mechanisms in acute
      transverse myelitis and related inflammatory disorders of the spinal cord have
      recently emerged. It is the purpose of this review to illustrate recent
      discoveries that shed light on this topic, relying when necessary on data from
      related diseases such as acute disseminated encephalomyelitis, Guillain-Barre
      syndrome and neuromyelitis optica. Developing a further understanding of how the
      immune system induces neural injury will depend upon confirmation and extension
      of these findings and will require multicenter collaborative efforts.

PMID- 12045736
TI  - Atypical inflammation in the central nervous system in prion disease.
AB  - The inflammatory response in prion diseases is dominated by microglial
      activation. Contrary to their profile in vitro none of the pro-inflammatory
      cytokines interleukin-1beta, interleukin-6, or tumour necrosis factor-alpha are
      significantly upregulated in the ME7 model of prion disease. However, two major
      inflammatory mediators are elevated: transforming growth factor-beta1 and
      prostaglandin E2. This cytokine profile is the same as that reported for
      macrophages during phagocytosis of apoptotic cells and indeed transforming growth
      factor-beta1 and prostaglandin E2 are responsible for the downregulated phenotype
      of these macrophages. Transforming growth factor-beta1 may also have roles in
      extracellular matrix deposition and in amyloidogenesis and may play a direct role
      in disease pathogenesis. There is also now evidence to suggest that a peripheral
      infection, and its consequent systemic cytokine expression, may drive central
      nervous system cytokine expression and perhaps exacerbate disease.

PMID- 12045737
TI  - Targeting the host inflammatory response in traumatic spinal cord injury.
AB  - Both acute and chronic inflammatory processes have been shown to influence
      outcome in experimental models of spinal cord injury. Although early inflammatory
      responses may participate in secondary injury processes, more delayed
      inflammatory events may be reparative. Therapeutic strategies that target these
      events are currently based on experimental findings that have clarified the
      cellular and molecular processes involved in the inflammatory response to injury.
      An increasing body of literature supports the hypothesis that acute inflammatory
      events are attenuated by therapeutic hypothermia and other anti-inflammatory
      strategies, whereas immune neuroprotection and axonal regeneration can be
      achieved by transfer of activated T cells or by treatment with therapeutic
      vaccines. These data are summarized in the present review.

PMID- 12045739
TI  - [CT guided adrenal biopsies: remaining indications?].
AB  - The need for adrenal gland biopsy has much decreased since CT and MR criteria
      have been introduced for further characterization of adrenal lesions. Several
      diagnostic criteria have been described for characterization of benign versus
      malignant adrenal lesions based on density measurements and contrast wash-out.
      Adrenal biopsy may be indicated for lesions that remain indeterminate in nature
      after CT and MRI. Such lesions include those with a percentage of wash-out near
      the 50% threshold or lesions that have increased in size at follow-up imaging in
      spite of their benign appearance based on density measurement at prior CT
      evaluation. The location of the adrenal glands has an impact on the technical
      difficulties during biopsy and the types of complications. Ipsilateral lateral
      decubitus seems the more logical approach and can be used for right or left
      adrenal lesions; this approach is generally well tolerated by patients.
      Biochemical evaluation should be performed prior to biopsy in order to exclude
      pheochromocytoma. The overall accuracy of adrenal biopsy, considering both
      positive predictive value and negative predictive value, compared to the gold
      standard is between 80 and 95% with a complication rate of about 10%.

PMID- 12045738
TI  - Anti-inflammatory strategies to prevent axonal injury in multiple sclerosis.
AB  - Axonal injury in multiple sclerosis has attracted considerable interest during
      the past few years. It has been demonstrated in association with inflammation
      within active lesions, but it is also present in normal-appearing white matter.
      Because axonal loss appears to be responsible for persistent neurological
      deficits in patients with multiple sclerosis, treatment strategies to prevent
      damage to neurites and restore function are of paramount importance in
      controlling the disease process. Some of the currently available immunomodulatory
      therapies may also reduce axonal damage, as demonstrated using improved imaging
      technologies, but the precise mechanisms that could protect axons during the
      inflammatory attack are yet to be identified. Factors that are involved in
      functional impairment of axonal conduction and those elements that are
      responsible for direct structural damage to the axon are both potential targets
      for therapeutic interventions.

PMID- 12045740
TI  - [Preoperative evaluation of renal carcinoma using multi-detector CT].
AB  - When laparoscopic nephrectomy is performed, the limited visibility of many
      anatomical structures requires additional pre-operative information. However,
      most of this information can be highlighted by Multislice-CT which depicts all
      the vascular structures while providing an essential road mapping for the
      surgeon. Besides underlining arterial abnormalities, this technique allows to
      depict venous pathways and tumoral invasion. This review illustrates the various
      potential applications of Multislice-CT in the evaluation of renal tumors.

PMID- 12045741
TI  - [Pain management with nerve root block under ct and neurostimulator guidance].
AB  - PURPOSE: To evaluate the efficacy of nerve roots block under CT and
      neurostimulator guidance for the management of pain. MATERIAL: and method. Nerve
      root blocks were performed in 27 patients (pudendal nerve, intercostal nerve,
      ilio-hypogastric nerve, thoracic and lumbar sympatholysis). These were performed
      with corticosteroids (Altim((R))) (20 patients) or phenol (7 patients). RESULTS:
      Seventeen patients (63%) had pain reduction during at least 15 days. The pain
      relief was longer with phenol. Complications appeared in the 3 lumbar
      sympatholysis (inguinal pain) and one of the thoracic sympatholysis (Claude
      Bernard Horner syndrome). CONCLUSION: The nerve root blocks seem to have some
      efficacy and a further evaluation is necessary to assess their impact on the
      ability of patients to return to work and their need for pain medication. When
      performing these procedures, one must be careful to avoid potential complications
      and verify that the procedure is needed.

PMID- 12045742
TI  - [Imaging of meningeal hemangiopericytomas].
AB  - PURPOSE: To study the imaging findings of meningeal hemangiopericytomas.
      MATERIAL: and method: Four cases of meningeal hemangiopericytomas are reported,
      two involving the spine and two intracranial in location. RESULTS: An extra-axial
      and heterogeneous pedunculated mass, without calcification should suggested a
      diagnosis of hemangiopericytoma especially if a bone erosion is noted; meningioma
      is the main differential diagnosis. CONCLUSION: CT scan as well as MR imaging are
      not specific but may provide findings consistent with a diagnosis of
      hemangiopericytoma. A long follow up of these patients is required because of
      frequent recurrences and delayed metastases.

PMID- 12045743
TI  - [Sinonasal sarcoidosis: CT evaluation].
AB  - Sarcoidosis uncommonly occurs in the sinonasal system and rarely in the absence
      of pulmonary disease. The mucosa of the septum and inferior turbinates are mostly
      affected. The diagnosis is based on endoscopic features, CT findings and finally
      the histologic appearance of non-caseating granulomas. The characteristic CT
      appearance consists of multiple mucosal nodules, mostly associated with various
      sinus fillings and inflammatory rhinitis. Septal perforation, nasal bone
      osteoporosis or destruction, cartilage destruction and saddle nose deformity can
      occur in patients with severe disease. However the diagnosis cannot be confirmed
      solely by CT and other causes of granulomatous inflammation have to be excluded
      using biopsy.

PMID- 12045744
TI  - [Treatement of colorectal obstruction with self-expanding metallic stents under
      fluoroscopic guidance].
AB  - PURPOSE: To prospectively evaluate fluoroscopic-assisted insertion of self
      expanding metallic stents before surgery or for palliative treatment of soft
      tissue colorectal obstruction. Materials and methods. From January 1999 to
      October 2000, 18 consecutive patients with colorectal obstruction were included
      in the study. Treatment with self-expanding metallic stent was either the first
      line of treatment before surgery (n=8) (group I) or purely palliative (n=10)
      (group II). Colic stenosis was located proximal to the sigmoid in seven cases.
      RESULTS: Technical success was achieved in 83.3% of cases and colic decompression
      was observed after 48 hours in all patients with a stent. Thirty days mortality
      and stent related complications were respectively 0% and 37.5% for group I, and
      20% and 50% for group II. All complications were minor except for one colic
      perforation by a guidewire. CONCLUSION: Stent insertion was effective and
      provided relief of colic obstruction in the majority of cases. Randomized studies
      would be necessary to demonstrate a definitive reduction in mortality and
      morbidity with this technique as compared to the classical surgical approach.

PMID- 12045745
TI  - [Isolated tuberculosis of the spleen. Report of a case].
AB  - Isolated tuberculosis of the spleen is rare and difficult to diagnose. The
      features and management of this disease are discussed based on one case. A 52
      year-old woman, presented with fever of unknown origin and splenomegaly.
      Ultrasonography and computed tomography demonstrated heterogeneous areas within
      the spleen. The diagnosis was made by a pathologic study of a splenic fragment
      obtained during laparotomy. When the spleen is the only organ involved by
      tuberculosis, the diagnosis is usually made by a pathologic study of splenic
      tissue obtained during laparotomy or percutaneous needle biopsy.

PMID- 12045746
TI  - [Pitfalls of hematopoietic growth factors on MR images].
AB  - We report the effects of hematopoietic growth factors on MR signal intensity of
      bone marrow in 2 children undergoing chemotherapy for musculoskeletal
      malignancies. The two patients with initially fatty marrow had signal intensity
      changes: diffuse decreased signal of the distal femoral metaphysis and patchy
      areas in the diaphysis of both tibia and fibula, simulating metastases. These
      changes coincided with dramatic increase in neutrophil counts. Technetium 99
      skeletal scintigraphy was normal. After a three year follow-up the patients are
      in good health.

PMID- 12045747
TI  - [Intermittent ureteropelvic junction obstruction and aberrant vessel to the lower
      pole of the kidney in children].
AB  - Intermittent ureteropelvic junction obstruction in children is a distinct
      clinical syndrome, it is often associated with an anteriorly crossing aberrant
      vessel to the lower pole of the kidney. The presence of these vessels increases
      the risk of complication and requires surgical management. CT scan is already the
      best exam to find these vessels in adults before treatment. It seems to be also
      efficient in children. This case report illustrates this indication.

PMID- 12045748
TI  - [Isolated gallbladder contusion following blunt trauma: a case report].
AB  - We report a case of isolated gallbladder contusion with hemobilia. Isolated
      gallbladder injury following blunt trauma is rare and early diagnosis is
      difficult. However, ultrasonography and computed tomography are valuable for
      investigating gallbladder injuries.

PMID- 12045749
TI  - [Quid? Peri-renal subcapsular hematoma].

PMID- 12045750
TI  - [Clinical evaluation of screening and diagnostic digital mammography].

PMID- 12045751
TI  - [Clinical and economical evaluation of stereotactic intracranial radiosurgery].

PMID- 12045752
TI  - Botulinum toxin (Botox Cosmetic) for frown lines.

PMID- 12045753
TI  - Topical pimecrolimus (Elidel) for treatment of atopic dermatitis.

PMID- 12045754
TI  - Spinal manipulation.

PMID- 12045755
TI  - Inhibitory control in adults with Attention-Deficit/Hyperactivity Disorder.
AB  - OBJECTIVES: Children with Attention-Deficit/Hyperactivity Disorder (ADHD) have
      been found to be deficient in inhibitory control. The purpose of this study was
      to determine if adults with ADHD are also deficient in this domain. METHODS: The
      performance of 18 adults with ADHD and 18 normal controls was compared on the
      Stop Signal Paradigm, which is a test of inhibitory control. RESULTS: The adults
      with ADHD performed more poorly on the Stop Signal Paradigm than did the normal
      controls. The ADHD subjects exhibited a longer latency to respond to the stop
      signal than did the control subjects. CONCLUSIONS: The individuals with ADHD
      tested in this study showed an inhibitory control deficit. The results suggest
      that a deficit in inhibitory control is central to ADHD.

PMID- 12045756
TI  - Further evidence for the diagnostic continuity between child and adolescent ADHD.
AB  - OBJECTIVE: To determine if there are differences in the clinical expression and
      correlates of ADHD between children and adolescents. METHOD: Subjects were 811
      boys and girls aged 6 to 17 with ADHD, and 132 gender- and age-matched controls.
      Blind raters, using DSM-III-R structured diagnostic interviews and psychometric
      measures, assessed psychiatric diagnoses, intellectual performance, social
      disability, and school failure. RESULTS: Children and adolescents with ADHD had
      very similar patterns of outcome in multiple domains of assessment, including
      comorbidity with conduct, mood and anxiety disorders, and school functioning.
      There was some evidence that the rate of ODD was greater in adolescents compared
      to children, and that this difference was greater in the control sample.
      CONCLUSIONS: These findings document the diagnostic continuity of ADHD between
      childhood and adolescence and support the inclusion of adolescent samples in ADHD
      research protocols.

PMID- 12045757
TI  - Attention-Deficit/Hyperactivity Disorder and methylphenidate: a dose-response
      analysis and parent-child comparison of somatic complaints.
AB  - The authors examined parent and child ratings of somatic complaints in 65
      children with Attention-Deficit/Hyperactivity Disorder (ADHD) who received four
      doses (5 mg, 10 mg, 15 mg, 20 mg) of methylphenidate (MPH) in the context of a
      double-blind, placebo controlled, within-subject (crossover) experimental design.
      Results indicated that parent and child ratings of somatic complaints decreased
      in a linear fashion from baseline levels as a function of increasing MPH dose and
      showed minimal variation across MPH conditions. Statistical comparisons of
      specific somatic complaints indicated minimal agreement between parents and
      children in contrast to the nearly identical parent-child dose-response curves.
      The paradoxical findings of fewer somatic complaints associated with MPH,
      importance of obtaining children's perceptions of MPH treatment, and implications
      for measuring somatic complaints are discussed.

PMID- 12045758
TI  - Driving anger and other driving-related behaviors in high and low ADHD symptom
      college students.
AB  - This study examined differences between college students with high and low
      symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Fifty-nine
      introductory psychology students completed ADHD diagnostic measures and were
      compared on measures of driving anger and driving anger expression; accident
      related, aggressive, and risky driving behaviors; general anger; and general
      anger expression. Results indicated high ADHD symptom college students experience
      more driving anger, display such anger in more hostile/aggressive ways, are more
      aggressive and risky on the road, experience more crash-related outcomes, are
      more generally angry, and tend to display anger in socially unacceptable ways.
      Results are discussed in regard to the understanding and treatment of ADHD.

PMID- 12045759
TI  - Distal jet appliance.

PMID- 12045760
TI  - Does science matter when selecting an office partner?

PMID- 12045761
TI  - Orthodontics and temporomandibular disorder: a meta-analysis.
AB  - As the importance of evidence-based health care has grown, meta-analysis has
      become more widely used in the medical and dental fields. In this meta-analysis,
      the relationship between traditional orthodontic treatment, including the
      specific type of appliance used and whether extractions were performed, and the
      prevalence of temporomandibular disorders (TMD) was investigated. After an
      exhaustive literature search of 960 articles, we found 31 that met the inclusion
      criteria (18 cross-sectional studies or surveys and 13 longitudinal studies). We
      divided and extracted data from the 31 articles according to study designs,
      symptoms, signs, or indexes. Due to severe heterogeneity, the results were
      summarized without further statistical analysis. The heterogeneous result might
      originate from lack of a universal diagnostic system and the variability of TMD.
      Because of heterogeneity, a definitive conclusion cannot be drawn. The data
      included in this comprehensive meta-analysis do not indicate that traditional
      orthodontic treatment increased the prevalence of TMD. It is apparent that a
      reliable and valid diagnostic classification system for TMD is needed for future
      research.

PMID- 12045762
TI  - Frankel appliance therapy and the temporomandibular disc: a prospective magnetic
      resonance imaging study.
AB  - This prospective clinical study assessed the effect of the Frankel Functional
      Regulator-II (FR-II) treatment on the position and shape of the articular disc of
      the temporomandibular joint. The sample included magnetic resonance images of 112
      temporomandibular joints taken initially (T1) and after 18 +/- 1 months (T2). The
      subjects were 56 white Brazilian children who were beginning their pubertal
      growth spurt. They had Class II Division 1 malocclusions and were selected from
      800 children in neighborhood schools. They were randomly dichotomized into either
      the treated group (treated with the FR-II for 18 months) or the control group
      (not treated during the observation period). Our findings showed a low prevalence
      (3.57%) of disc displacement in the 112 temporomandibular joints. Mandibular
      propulsion with the FR-II had no unfavorable effect on the temporomandibular
      joints of the treated group; 100% of the patients kept an upper and interposed
      disc position (closed and open mouth, respectively) at T1 and T2. The control
      group had 7.1% partial anterior medial disc displacement, both at T1 and T2.
      Regarding disc morphology, the control group showed biconcave-shaped discs in
      82.1% of the joints, statistically similar to the treated group (89.3%) at the
      beginning of the observation period. At T2, the articular disc morphology of the
      control group was unchanged, but that of the treated group was significantly more
      normal (P =.016), progressing from nonbiconcave at T1 (10.7%) to biconcave at T2
      (100%). Our results showed that disc displacement is not a complication of
      functional appliance therapy; in fact, such treatment might help some children
      with incipient temporomandibular disorders.

PMID- 12045763
TI  - Comparative study of the Frankel (FR-2) and bionator appliances in the treatment
      of Class II malocclusion.
AB  - The purpose of this investigation was to compare the dentoalveolar and skeletal
      cephalometric changes produced by the Frankel (FR-2) and bionator appliances in
      persons with Class II malocclusion. Lateral cephalograms were available for 66
      patients of both sexes, who were divided into 3 groups of 22. The control group
      included untreated Class II children, with an initial mean age of 8 years 7
      months; they were followed without treatment for 13 months. The FR-2 appliance
      group had an initial mean age of 9 years; those children were treated for a mean
      period of 17 months. The bionator group initially had a mean age of 10 years 8
      months; on average, they were treated for 16 months. The results demonstrated no
      significant changes in maxillary growth during the evaluation period. Both
      appliances showed statistically significant increases in mandibular growth and
      mandibular protrusion, with greater increases in patients treated in the bionator
      group. Both experimental groups showed an improvement in the maxillomandibular
      relationship. There were no significant changes in growth direction, while the
      bionator group had a greater increase in posterior facial height. Both appliances
      produced similar labial tipping and protrusion of the lower incisors, lingual
      inclination, retrusion of the upper incisors, and a significant increase in
      mandibular posterior dentoalveolar height. The major treatment effects of
      bionator and FR-2 appliances were dentoalveolar, with a smaller, but significant,
      skeletal effect.

PMID- 12045764
TI  - Effect of steam versus dry-heat sterilization on the wear of orthodontic ligature
      cutting pliers.
AB  - The purpose of this study was to compare the wear of orthodontic ligature-cutting
      pliers after multiple cycles of cutting stainless steel ligature wire (.025 mm)
      and sterilizing with dry heat or steam autoclave. Fifty ligature-cutting pliers
      with stainless steel inserts were randomly divided into 2 equal groups to be
      sterilized in either dry heat or steam autoclave. Each plier was subjected to a
      series of ligature wire cuts followed by the assigned sterilization method. The
      amount of wear at the tip of each plier in both groups was measured with a stereo
      microscope system and digital photomicrography. Wear was defined as the
      difference in initial length from a marked reference line to the tip of the plier
      minus the length after 6 and 12 cycles of use and sterilization. There was no
      significant difference in the mean wear at the tip of the pliers between the 2
      groups. It appears that there is no need to maintain both sterilization systems,
      dry heat and steam autoclave, in the orthodontic office. Steam autoclave
      sterilization can be used with no deleterious effects on the pliers if they are
      manufactured with stainless steel inserts.

PMID- 12045765
TI  - Comparison of resistance to sliding between different self-ligating brackets with
      second-order angulation in the dry and saliva states.
AB  - Resistance to sliding was investigated for 3 self-ligating brackets having
      passive slides and 3 self-ligating brackets having active clips. Four of these
      products are currently marketed, and 2 are of historic interest. For all cases,
      an 0.018 x 0.025-in stainless steel archwire was drawn through each bracket at a
      rate of 10 mm/min over a distance of 2.5 mm. For each bracket, the resistances to
      sliding were measured at 14 second-order angulations, which ranged from -9
      degrees to +9 degrees. Both the dry and the wet (human saliva) states were
      evaluated at 34 degrees C. From dimensional measurements, the critical contact
      angles for binding were determined for all products and ranged from 3 degrees to
      5 degrees. Below each characteristic critical angle, brackets with passive slides
      exhibited negligible friction; brackets with active clips exhibited frictional
      forces as great as 50 cN (50 g). Above each critical angle, all brackets had
      elastic binding forces that increased at similar rates as angulation increased
      and were independent of bracket design. Generally speaking, at second-order
      angulations that exceeded the critical angle, brackets with active clips that had
      a low critical angle had more resistance to sliding than did brackets with active
      clips that had a higher critical angle. Brackets with passive slides that had a
      high critical angle exhibited the lowest resistance to sliding, but could do so
      at a cost of some loss of control. Nonetheless, self-ligating brackets represent
      a compromise between friction and control; ie, self-ligating brackets produce
      frictional forces that are more reproducible than do conventionally ligated
      stainless steel brackets but without the potential control problems associated
      with Begg-style brackets.

PMID- 12045766
TI  - Load-deflection characteristics of superelastic nickel-titanium orthodontic
      wires.
AB  - Previous mechanical testing of orthodontic wires has, in many cases, failed to
      simulate some key features of the clinical environment. The purpose of this study
      was to investigate the load-deflection characteristics of 7 different 0.016-in
      initial alignment archwires (Twistflex, NiTi, and 5 brands of heat-activated
      superelastic nickel-titanium [HASN]) with modified bending tests simulating a
      number of conditions encountered clinically. Load-deflection tests were carried
      out on the wires with 5 different model designs, and data from selected points on
      the unloading phase of the generated graphs were statistically analyzed. Wire
      deflection was carried out at 3 temperatures (22.0 degrees C, 35.5 degrees C, and
      44.0 degrees C) and to 4 deflection distances (1 mm, 2 mm, 3 mm, and 4 mm).
      Rankings were derived according to statistically significant differences in each
      test situation. The effects of model, wire, and temperature variation were all
      statistically significant. Twistflex and the 5 HASN wires produced a range of
      broadly comparable results, and NiTi gave the highest unloading values. Model
      rankings indicated that self-ligating Twin-Lock brackets produced lower friction
      than regular edgewise brackets. The authors recommend using the rankings from the
      mechanical test simulations to predict possible clinical performance of
      archwires.

PMID- 12045767
TI  - In vivo bracket retention comparison of a resin-modified glass ionomer cement and
      a resin-based bracket adhesive system after a year.
AB  - Glass ionomer orthodontic adhesives cause less enamel demineralization during
      fixed orthodontic appliance treatment than do traditional resin-based products.
      An in vivo randomized clinical trial was performed comparing the clinical
      performance of a resin-modified glass ionomer (RMGI) adhesive with a no-mix,
      resin-based (the control) adhesive over a 12-month period. The split-mouth
      technique was used to analyze bracket retention, bracket failure causes, and mode
      of failure for both adhesives in 61 patients. Bracket-failure rates were 10% for
      the RMGI and 4% for the resin-based adhesive. Both adhesives had 4 times more
      bracket failures when opposing occlusion was present. The resin-based product
      demonstrated a higher proportion of resin-to-enamel adhesive failures than did
      the RMGI. Compared with the resin-based adhesive, the RMGI-bracketed teeth showed
      improved clinical performance, no enamel surface loss, less enamel
      demineralization, and faster adhesive removal. However, the RMGI had a 2.6 times
      greater bracket-failure rate than did the resin-based product.

PMID- 12045768
TI  - The relationship between acid-etch patterns and bond survival in vivo.
AB  - The aim of this study was to investigate the relationship between acid-etch
      quality and bond survival in vivo. The subjects were 29 orthodontic patients.
      High-resolution silicone impressions were taken of the buccal tooth surfaces
      after etching for 30 seconds with 37% phosphoric acid. The impressions were
      replicated in epoxy resin and examined under high magnification in a scanning
      electron microscope. A 4-point classification system and histometric techniques
      were used to evaluate etch patterns on the enamel surfaces where orthodontic
      brackets were to be bonded. After impressions were made, all teeth (including
      first molars) were bonded with 0.022-in Andrews' prescription brackets ("A"
      Company, San Diego, Calif) and Right-On composite (TP Orthodontics, Leeds,
      England). The first date of bond failure for each tooth was recorded; it varied
      from 1 to 806 days. An ideal etch pattern was found on less than 5% of the
      orthodontic bonding area; type C pattern (pitted enamel surface) occupied the
      greatest area. Overall, the failure rate was 55.8% over 26 months; the greatest
      failure rate occurred in first molars. Multiple regression analysis revealed a
      positive and statistically significant relationship between the area occupied by
      ideal etch type and the length of survival of the bond (P <.001).

PMID- 12045769
TI  - A comparison of shear bond strengths of orthodontic brackets using various light
      sources, light guides, and cure times.
AB  - The objective of this study was to evaluate the effects of different cure times,
      light sources, and light guides on shear bond strength of orthodontic brackets
      bonded with Transbond XT (3M Unitek, Monrovia, Calif) to bovine enamel.
      Specifically, the Power Slot (Reliance Orthodontic Products, Itasca, Ill) light
      guide was placed on 4 visible light sources to compare shear bond strengths and
      recommended cure times with the light guides provided with each light source. We
      randomly divided 240 bovine mandibular incisors into 16 groups; each group
      consisted of 15 teeth mounted in an acrylic block. Each group of teeth was
      polymerized with a specific light and light guide combination. Eight groups were
      sheared after 5 minutes and the remaining 8 groups after 24 hours. After bonding,
      all brackets were subjected to a shear force with a testing machine. Overall,
      there was a significant increase in bond strengths of the 24-hour groups compared
      with the 5-minute shearing groups. However, there were no statistical differences
      (P =.05) within the 24-hour test groups or the 5-minute test groups. The results
      of this study indicate that, compared with standard light guides, the Power Slot
      and the Turbo Tip (Ormco Sybron Dental Specialties, Orange, Calif) light guides
      can significantly reduce the curing times (10 seconds per bracket; 5 seconds each
      from mesial and distal) without affecting their shear bond strengths. Therefore,
      the Power Slot and the Turbo Tip light guides with their collimation of visible
      light to increase its intensity can be recommended as advantageous alternatives
      for curing composite resins for orthodontic bonding procedures.

PMID- 12045770
TI  - Etching conditions for resin-modified glass ionomer cement for orthodontic
      brackets.
AB  - This study reports the tensile bond strength of orthodontic eyelets (RMO, Inc,
      Denver, Colo) bonded to human extracted teeth with a resin-modified glass ionomer
      cement (RMGIC) (Fuji Ortho LC, GC America, Alsip, Ill) and various acid etchants
      (Etch-37 and All-Etch, Bisco, Schaumburg, Ill; Ultra Etch, 3M Unitek, St Paul,
      Minn) for enamel preparation before bonding. The enamel etch conditions were as
      follows: 37% phosphoric acid with silica; 37% phosphoric acid, silica-free; 10%
      phosphoric acid, silica-free; 10% polyacrylic acid; and unetched enamel. Bond
      strength was measured by pulling in tension on the eyelet with a 0.018-in steel
      wire perpendicular to the enamel surface with a testing machine (Instron model
      1125, Canton, Mass) at a speed of 2 mm/min. A light-cured resin cement (Transbond
      XT, 3M Unitek, Monrovia, Calif) applied to enamel etched with 37% phosphoric acid
      containing silica served as a control. Each group included 30 specimens. The
      Weibull distribution (m) was used for statistical analysis with a 90% CI. The
      different etchants used with RMGIC did not affect tensile bond strength. The
      resin cement group had the highest tensile strength. Significantly lower bond
      strengths were observed when glass ionomer cement was used to bond orthodontic
      attachments to nonetched teeth. However, unlike resin cement, RMGIC can bond
      effectively to etched teeth in a moist environment without an additional bonding
      agent.

PMID- 12045771
TI  - The effect of repeated bonding on the shear bond strength of different
      orthodontic adhesives.
AB  - One problem clinicians face during treatment is bracket failure. In a busy
      orthodontic practice, a significant number of teeth will need to be rebonded. The
      purpose of this study was to evaluate the effect of repeated bonding with 2
      different adhesives, a composite and a cyanoacrylate, on the shear bond strength
      of orthodontic brackets. Thirty-one freshly extracted human molars were
      collected. Brackets were bonded with 1 of the orthodontic adhesives according to
      the manufacturer's instructions. In group I, the teeth were etched with 37%
      phosphoric acid, a sealant was applied, and the brackets were bonded with
      Transbond XT (3M Unitek, Monrovia, Calif) and light cured for 20 seconds. In
      group II, the teeth were etched with 35% phosphoric acid, and the brackets were
      bonded with SmartBond (Gestenco International, Gothenburg, Sweden). In each
      group, the teeth were bonded and debonded 3 times with the same adhesive. At each
      sequence, the brackets were removed within 30 minutes after bonding to simulate
      the clinical condition at which a newly bonded bracket is tied to the archwire.
      Student t tests and the analysis of variance repeated measure were used to
      compare the shear bond strength between adhesives and within each adhesive at
      different debonding sequences. The results indicated that, at the first debonding
      sequence, the 2 adhesives did not have significantly different shear bond
      strengths. Between debonding sequence 1 and 2, there was a significant (P
      <or=.05) decrease in the shear bond strength of both adhesives. SmartBond
      decreased from x = 5.7 +/- 3.8 MPa to x = 2.2 +/- 2.6 MPa, and Transbond
      decreased from x = 6.1 +/- 3.4 to x = 4.1 +/- 2.3 MPa. When the 2 adhesives were
      compared at the second debonding sequence, the shear bond strength of Transbond
      was significantly greater than that of SmartBond (P =.046). Between debonding
      sequences 2 and 3, there were no significant differences either between the
      adhesives or in the change within each adhesive. The highest values for shear
      bond strength were obtained after the initial bonding. Rebonded teeth had
      significantly lower shear bond strength. The composite adhesive had a higher
      shear bond strength than the cyanoacrylate adhesive at the second
      bonding/debonding sequence but not at the third. The changes in bond strength
      after repeated bonding may be related to changes in the morphologic
      characteristics of the tooth surface caused by adhesive remnants.

PMID- 12045772
TI  - A comparison of in vitro enamel demineralization potential of 3 orthodontic
      cements.
AB  - The objective of this in vitro study was to compare resistance to enamel
      demineralization after banding with 3 orthodontic cements. The 3 orthodontic
      cement groups and the nonbanded control group were evaluated for cariopreventive
      potential. One hundred twenty extracted human molars were selected for banding,
      embedded in resin blocks, and randomly assigned to the following 4 groups: zinc
      phosphate cement, zinc polycarboxylate cement, resin-modified glass ionomer
      (RMGI), and nonbanded control. Orthodontic bands were placed and cemented;
      specimens were stored in artificial saliva at 37 degrees C for 30 days,
      thermocycled for 24 hours, and then debanded with a customized band-removal
      device attached to a universal testing machine. The cement was hand removed, and
      2 coats of nail varnish were applied to the teeth, leaving a 2 x 2-mm window
      exposed on the buccal surface of the mesiobuccal cusp. The teeth were stored in
      lactic acid-gelatin solution for 4 weeks at 37 degrees C to develop simulated
      white spot decalcification in the window. The teeth were subjected to dye (10%
      methylene blue) for 24 hours and then sectioned through the window. The depth of
      dye penetration was determined and used as a measure of the cariopreventive
      effect of the banding cement. Data were analyzed with a 1-way ANOVA and a Tukey
      test for the multiple comparisons. Dye penetration occurred as follows: the zinc
      phosphate and control groups were about the same; there was less dye penetration
      with the zinc polycarboxylate, and the least with the resin-modified glass
      ionomer. The 2 fluoride-releasing cements (zinc polycarboxylate and RMGI)
      demonstrated less demineralization than the zinc phosphate in vitro and might
      provide greater protection from demineralization around a band periphery in
      clinical settings.

PMID- 12045773
TI  - Treatment of a Class II malocclusion with deep overbite.

PMID- 12045774
TI  - Invisalign A to Z.

PMID- 12045775
TI  - Litigation, legislation, and ethics. The limits of informed consent.

PMID- 12045777
TI  - Distal ulcerative colitis refractory to rectal mesalamine: role of transdermal
      nicotine versus oral mesalamine.
AB  - BACKGROUND: Distal ulcerative colitis usually responds to treatment with rectal
      mesalamine, but the management of refractory cases is poorly defined. AIM: To
      evaluate the possible therapeutic benefit of transdermal nicotine versus oral
      mesalamine. PATIENTS AND METHODS: Thirty patients with left-sided ulcerative
      colitis unresponsive to treatment with a mesalamine 4 g enema at bedtime were
      randomly allocated to additional therapy with either transdermal nicotine 15 mg
      daily or oral mesalamine 800 mg tid for four weeks. Clinical remission was
      evaluated by Rachmilewitz's activity index and confirmed by sigmoidoscopy.
      RESULTS: Remission was observed in 12 of 15 patients receiving additional
      treatment with nicotine and in five of 15 patients receiving additional treatment
      with oral mesalamine (P=0.027). CONCLUSIONS: The addition of transdermal nicotine
      to treatment with mesalamine enemas is significantly superior to combined therapy
      with oral and rectal mesalamine in patients with distal ulcerative colitis
      refractory to rectal mesalamine alone.

PMID- 12045778
TI  - Natural history of C282Y homozygotes for hemochromatosis.
AB  - PURPOSE: To study the clinical outcomes of subjects who are homozygous for the
      C282Y mutation of the hemochromatosis gene. SUBJECTS AND METHODS: All patients
      referred to a tertiary referral centre for hemochromatosis were included. The
      study also included 16 C282Y homozygotes detected in a population screening
      study. RESULTS: The study comprised 277 C282Y homozygotes, including 16
      nonexpressing C282Y homozygotes. The mean follow-up period was 7.3 years (range
      zero to 44 years). The actuarial survival rates of C282Y homozygotes at five, 10
      and 20 years were 95%, 93% and 66%, respectively. Life-threatening diseases
      (cirrhosis, hepatocellular carcinoma, diabetes, heart disease) were present in
      36% of male C282Y homozygotes and 19% of female C282Y homozygotes. Cirrhosis of
      the liver and diabetes were the major clinical symptoms affecting long term
      survival. Only one nonexpressing homozygote required venesection therapy during
      the follow-up period. CONCLUSIONS: Long term survival is excellent in C282Y
      homozygotes diagnosed and treated before the development of cirrhosis and
      diabetes.

PMID- 12045779
TI  - Nonalcoholic steatohepatitis in nondiabetic obese patients.
AB  - BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a major disorder in patients
      with persistent changes in aminotransferase activity who test negative for viral
      markers and autoantibodies. Although NASH has been correlated with obesity, no
      study has been carried out exclusively with nondiabetic obese patients.
      OBJECTIVES: To evaluate the occurrence of NASH in obese patients without diabetes
      mellitus and to assess the severity of histological involvement of the liver.
      PATIENTS AND METHODS: Serum aminotransferase levels were evaluated in 912 obese
      patients seen at an outpatient clinic in Porto Alegre, Brazil, from 1997 to 1999.
      Sixty-eight patients were found to have altered aminotransferase levels in more
      than one test. Thirty-five patients were excluded due to the presence of diabetes
      mellitus (n=12), the presence of viral markers (n=11), alcohol consumption (n=8)
      and the use of hepatotoxic drugs (n=4). NASH was diagnosed when histological
      findings revealed macrovesicular steatosis associated with lobular inflammatory
      infiltrate and hepatocellular injury. RESULTS: Of the 912 obese patients studied,
      33 patients with altered aminotransferase levels underwent liver biopsy. Four
      patients were excluded because they had steatosis only; the remaining 29 patients
      (3.18%) fulfilled the diagnostic criteria established for NASH. The mean age of
      the 29 patients was 42.2 +/- 11.9 years; 65.52% of the patients were women.
      Grading of histological findings revealed mild disease in 58.6% of cases;
      important proliferation of fibrous tissue was absent in most cases. CONCLUSIONS:
      NASH is a common disease among nondiabetic obese patients with altered
      aminotransferase levels, and it usually manifests as a mild clinical condition,
      although more severe lesions may be observed.

PMID- 12045780
TI  - Brunner's gland hamartoma: a rare cause of gastrointestinal bleeding -- case
      report and review of the literature.
AB  - An unusual cause of upper gastrointestinal bleeding is described in a previously
      healthy 45-year-old man who was admitted to hospital with weakness and fatigue,
      and had experienced an episode of melena two days before admission. His medical
      and surgical history was unremarkable. Upon admission to hospital, he showed
      evidence of iron-deficiency anemia, with a hemoglobin concentration of 61 g/L
      (normal range 135 to 175 g/L), a mean corpuscular volume of 73 fL (normal range
      85.0 to 95.0 fL) and a ferritin concentration of 1.0 microg/L (normal range in
      males 15 to 400 microg/L). Upper gastrointestinal endoscopy revealed a 3.5 cm
      ulcerated submucosal mass in the third portion of the duodenum, for which mucosal
      biopsies were nondiagnostic. A subsequent endoscopic ultrasound revealed a 2.7 x
      4.0 cm hyperechoic, cystic, submucosal tumour in the third portion of the
      duodenum. Endoscopic ultrasound-guided fine needle aspiration revealed no
      malignant cells. The patient eventually underwent a resection of the third
      portion of his duodenum. Surgical pathology revealed that this tumour was a
      Brunner's gland hamartoma, 4.5 cm in its greatest dimension.

PMID- 12045781
TI  - Nonalcoholic steatohepatitis: more than just being fat.

PMID- 12045782
TI  - When acid suppression is not enough: endoscopy and GERD.

PMID- 12045783
TI  - Evolving concepts of reflux: the ups and downs of the LES.
AB  - The common denominator for virtually all episodes of gastroesophageal reflux in
      health and disease is the loss of the barrier that confines the gastric
      environment to the stomach. Factors important in the function of the barrier are
      its pressure, length and position. In early reflux disease, overeating, gastric
      distention, delayed emptying and aerophagia lead to transient losses of the
      barrier. A permanent loss results from inflammatory injury to the muscle of the
      barrier with free flow of gastric juice into the esophageal body and its
      subsequent injury. Corrective therapy requires augmentation or restoration of
      barrier function.

PMID- 12045784
TI  - Chronic gastrointestinal inflammation and cerebrovascular events.

PMID- 12045785
TI  - A model for partnership and research between the CAG and sponsors.

PMID- 12045787
TI  - Angiotensin blockade in type 2 diabetes: what the new evidence tells us about
      renal and cardiac complications.
AB  - Diabetes has long been recognized as a risk factor for heart disease. Recent
      evidence has brought to light complex interactions that seem to influence both
      the renal and the vascular complications of diabetes. The use of angiotensin
      converting enzyme inhibitors and angiotensin receptor blockers has been shown to
      ameliorate renal and cardiac risks in both type 1 and type 2 diabetes to a degree
      that is disproportionate to blood pressure-lowering effects. The judicious use of
      these agents can materially improve the prognosis for patients with diabetes.

PMID- 12045788
TI  - Angiotensin receptor blockers: powerful evidence with cardiovascular outcomes?
AB  - Angiotensin receptor blockers (ARBs) were developed to better antagonize the
      effects of chronic overactivation of angiotensin II. In clinical studies, ARBs
      have consistently been shown to be more tolerable than angiotensin-converting
      enzyme inhibitors (ACEis). Although many studies evaluating the benefits of ARBs
      in clinical practice are underway, relatively little information exists as to
      their benefits concerning cardiovascular events. In heart failure patients with
      ACEi intolerance, ARBs may improve survival. In patients who can tolerate an
      ACEi, ARBs reduce hospitalization. Due to a possible detrimental interaction when
      an ARB is added to the treatment of patients already taking an ACEi and a beta
      blocker, the use of ARBs in such heart failure patients is not generally
      indicated. ARBs also preserve renal function and may reduce cardiovascular events
      in patients with pre-existing renal dysfunction and type 2 diabetes. However,
      there is no convincing evidence that ARBs improve the survival of these patients.
      Thus, ARBs should be used on their own merits and should not be used as
      substitutes for ACEis in this patient population. Studies to establish the status
      of ARBs in the treatment and prevention of cardiovascular diseases are ongoing,
      but until they are completed, care should be taken in extrapolating the effects
      of ARBs to those of ACEis.

PMID- 12045789
TI  - Vascular changes in hypertension in response to drug treatment: Effects of
      angiotensin receptor blockers.
AB  - Large and small arteries are remodelled in hypertension - their structure,
      function and mechanics are altered. These changes contribute to elevated blood
      pressure and to the complications of hypertension. The present paper concentrates
      on small (resistance) artery changes in hypertension. In hypertension, these
      vessels exhibit a form of remodelling known as 'eutrophic' remodelling, in which
      smooth muscle cells are restructured around a smaller lumen, without true
      hypertrophy, particularly in milder forms of hypertension. Changes in these small
      arteries are the first manifestation of target organ damage in patients with
      hypertension. In more severe forms of hypertension and in secondary hypertension,
      hypertrophic remodelling has been reported. Stiffness of the vessel wall may be
      decreased initially; later, as hypertension becomes more severe, the wall of
      resistance vessels may become stiffer. Endothelial dysfunction occurs in a
      percentage of patients, similar to the prevalence of left ventricular
      hypertrophy. Interruption of the renin-angiotensin system may correct many of
      these abnormalities. The present report investigated the effects of angiotensin
      type 1 (AT1) receptor antagonists on small arteries of hypertensive patients
      compared with the beta-blocker atenolol in different studies. Beta-blocker
      treatment did not modify either the structure or the function of small arteries
      in contrast to the AT1 antagonist losartan in a double-blind, randomized, one
      year study. Patients previously treated with atenolol to lower blood pressure,
      but whose small artery structure and function did not improve, were examined.
      These hypertensive patients were switched to the AT1 antagonist irbesartan for
      one year. Gluteal subcutaneous biopsies showed that the structure and endothelial
      function of small arteries that had remained altered by atenolol treatment were
      corrected by irbesartan treatment, although blood pressure control with
      irbesartan was identical to that previously achieved with atenolol. Improved
      outcomes in clinical trials using angiotensin-converting enzyme inhibitors and
      AT1 receptor antagonists may be a result of the vascular protective effects
      offered by these agents.

PMID- 12045791
TI  - [Attributed risk to smoking for lung cancer, laryngeal cancer and esophageal
      cancer].
AB  - OBJECTIVE: Lung, laryngeal and esophageal cancers have smoking as one of their
      main risk factors. The objective of this study was to evaluate the population
      attributed risk (PAR) of smoking for these forms of cancer. METHODS: The study
      was based in three case-control studies conducted in medium size cities in
      Brazil. Incident cases of lung cancer, laryngeal cancer and esophageal cancer
      seen at a hospital setting and diagnosed through biopsy were analyzed; controls
      were hospitalized patients with another diagnoses. Smoking was the exposure
      factor measured at three levels: non-smokers, former smokers and smokers, which
      were defined using a questionnaire applied by trained interviewers. For effect
      measure, odds ratio was used and the populational attributed risk for smoking was
      then calculated for a 95% CI. RESULTS: A total of 122 lung cancer cases and 244
      controls, 50 cases of laryngeal cancer and 48 cases of esophageal cancer, and 96
      controls for both of them were studied. The prevalence of smoking exposure was
      34%, which is the overall prevalence of smoking in this city's adult population.
      Odds ratios (OR) for the PAR analysis were the adjusted OR for confounding
      variables from each study. Lung cancer PAR was 63% (95% IC, 0.58-0.68) for former
      smokers and 71% (95%IC, 0.65-0.77) for smokers. Larynx cancer PAR was 74% (95%
      IC, 0.70-0.78) and 86% (95%IC, 0.81-0.85) for former smokers and smokers,
      respectively. Esophageal cancer PAR was 54% (95%IC, 0.46-0.62) for smokers.
      CONCLUSION: Smoking is an avoidable risk factor and smoking cessation could be
      responsible for significant reductions in the incidence of these three forms of
      cancer.

PMID- 12045792
TI  - [Diabetes mellitus mortality among elderly as an underlying or secondary cause of
      death].
AB  - OBJECTIVE: To analyze diabetes mellitus-related mortality among elderly and the
      rate of undereporting of diabetes mellitus as a cause of death when statistical
      data on diabetes exclusively on the underlying cause of death are considered.
      METHODS: A total of 2.974 death certificates of elderly people living in a
      housing project in the city of Rio de Janeiro were revised. The study period was
      1994. Of them, 291 deaths were due to diabetes mellitus, 150 as the underlying
      and 141 as the secondary cause of death. The proportion of deaths where diabetes
      was stated as the underlying cause in relation to the total of diabetes deaths
      was calculated globally and categorized by sex and age groups. RESULTS: Of the
      291 deaths studied, 138 (47.4%) were men and 153 (52.6%) were women. Mortality
      rates showed a continuous age increase and were higher among men, though sex
      difference was smaller when only the underlying cause was considered. It was
      found a higher proportion of deaths (22%) occurring at home. Overall rate of
      diabetes deaths as the underlying cause was 51.5%, with higher rates seen in
      women. CONCLUSIONS: The analysis of mortality statistics based exclusively on the
      underlying cause of death can yield misleading profiles due to unrandomized
      underreporting. There is a need of further studies with diabetic elderly cohorts
      for a more accurate mortality analysis in this population group.

PMID- 12045793
TI  - [Malnutrition mortality in the elderly, southeast Brazil, 1980-1997].
AB  - OBJECTIVE: To assess the frequency of nutritional disturbances as cause of death
      in elderly. METHODS: Female and male subjects aged 60 years and more were
      selected from municipalities of the southeastern region between 1980 and 1997.
      Data was collected from death certificates provided by the Death Data System
      (1980-1998) and the population size was estimated using data provided by the
      Center for Regional Development and Planning (Cedeplar). Death categorization was
      performed using the ICD-9 (260 to 263.9) for the period 1980 to 1995 and ICD-10
      (E40 to E46) for recent years. RESULTS: In Brazil, between 1980 and 1997, there
      were 36,955 deaths associated to malnutrition among elderly. The southeast region
      concentrates the largest number of deaths, 23,968 (64.9%). In the state of Sao
      Paulo, there were 11,067 deaths caused by malnutrition in elderly and in the
      state of Rio de Janeiro, 7,763. These two regions are responsible for the highest
      values observed for the region. There are higher death proportions and mortality
      rates among subjects aged 70 years and more than in subjects of any sex of the
      age group 60 to 69 years. CONCLUSION: The preliminary results of the study raise
      some issues as follows: the role of malnutrition as an associated cause of death;
      the trend of increased number of deaths for malnutrition among elderly people;
      distinctive death characteristics among states in the same geographic region.
      Statistical analysis such as time series analysis might explain better these
      issues. There is a need to further study the role of malnutrition among elderly
      aged 60 years and more to establish adequate intervention programs.

PMID- 12045794
TI  - [Asthma mortality in the city of Sao Paulo, Brazil].
AB  - OBJECTIVE: To quantify and compare asthma mortality rates as the main cause of
      death, taking into consideration the following variables: sex, age and
      seasonality. METHODS: Data was collected from all death certificates coded 493 of
      people aged 5 to 34 years in the periods of 1983-5 and 1993-5 in the city of Sao
      Paulo, SP, Brazil. Data analysis was performed by directly comparing death rates
      and identifying the odds ratio trend and directly comparing the numbers of asthma
      deaths. RESULTS: There was no increase in asthma mortality rates for the study
      periods. There was no difference between men and women. A greater number of
      deaths in the age group 20 to 34 years were observed. Seasonality was more
      evident in the first period studied. CONCLUSIONS: Differing from reports in other
      countries, the results did not show any increase in asthma mortality rates, The
      variable sex didn't seem to interfere with mortality. Deaths are more frequent
      among young adults, and their risk may be 9 times greater than that of young
      children. Deterioration of social and economic issues and health care services
      and even climatic changes may have been implicated in the absence of seasonality
      as a risk factor for asthma mortality. The disease by itself is not considered by
      many health professionals as critical in order to explain the chain of events
      that lead to death.

PMID- 12045795
TI  - Rash after measles vaccination: laboratory analysis of cases reported in Sao
      Paulo, Brazil.
AB  - OBJECTIVE: The clinical differential diagnosis of rash due to viral infections is
      often difficult, and misdiagnosis is not rare, especially after the introduction
      of measles and rubella vaccination. A study to determine the etiological
      diagnosis of exanthema was carried out in a group of children after measles
      vaccination. METHODS: Sera collected from children with rash who received measles
      vaccine were reported in 1999. They were analyzed for IgM antibodies against
      measles virus, rubella virus, human parvovirus B19 (HPV B19) using ELISA
      commercial techniques, and human herpes virus 6 (HHV 6) using immunofluorescence
      commercial technique. Viremia for each of those viruses was tested using a
      polimerase chain reaction (PCR). RESULTS: A total of 17 cases of children with
      exanthema after measles immunization were reported in 1999. The children, aged 9
      to 12 months (median 10 months), had a blood sample taken for laboratory
      analysis. The time between vaccination and the first rash signs varied from 1 to
      60 days. The serological results of those 17 children suspected of measles or
      rubella infection showed the following etiological diagnosis: 17.6% (3 in 17) HPV
      B19 infection; 76.5% (13 in 17) HHV 6 infection; 5.9% (1 in 17) rash due to
      measles vaccine. CONCLUSIONS: The study data indicate that infection due to HPV
      B19 or HHV 6 can be misdiagnosed as exanthema due to measles vaccination.
      Therefore, it is important to better characterize the etiology of rash in order
      to avoid attributing it incorrectly to measles vaccine.

PMID- 12045796
TI  - [Epidemiology of dengue infection in Ribeirao Preto, SP, Brazil].
AB  - OBJECTIVE: To assess dengue transmission in a correctional facility for juvenile
      delinquents in Ribeirao Preto, state of Sao Paulo, Brazil. METHODS: A serological
      and virology investigation was carried out among inmates and employees of a
      correctional facility for juvenile delinquents in Ribeirao Preto, Brazil. The
      study population consisted of 105 inmates and 91 employees representing 89% of
      the exposed. The collected blood was stored and processed using MAC-ELISA and
      virus isolation. A questionnaire was applied to each subject at the time of blood
      collection. RESULTS: Of the total of blood samples collected (n=196), 42 (21.4%)
      were positive for IgM antibodies and 43 (21.9%) for IgG antibodies; of which, 15
      were both IgM and IgG positive and 28 (14.3%) were IgG positive only. Serotype 1
      dengue virus was isolated in 5 samples. Out of 42 IgM positive samples, 14
      (33.0%) subjects did not have any physical complaints. The incidence rate was
      23.8% and 18.6% among inmates and employees, respectively. The first cases in the
      facility were reported in 1997 and the last ones in March 1997 though results are
      suggestive of an earlier onset of transmission. CONCLUSIONS: The high incidence
      rate of dengue infection can be explained by the high population density of the
      facility, high Aedes aegypti infestation, high numbers of asymptomatic subjects,
      and a higher transmission of disease in a closed setting.

PMID- 12045797
TI  - [Climate and the superimposed distribution of Aedes aegypti and Aedes albopictus
      on infestation of Sao Paulo State, Brazil].
AB  - OBJECTIVE: To study the influence of climatic factors and superimposed
      distribution of Aedes aegypti and Aedes albopictus populations on their
      geographic dispersal in the state of Sao Paulo. METHODS: Data from government
      agencies on Ae. aegypti and Ae. albopictus foci and their distribution throughout
      counties of the state of Sao Paulo year by year, from 1985 to 1995, were
      obtained. Temperatures and rainfall data were also collected. Two indicators were
      used: infestation and rate. RESULTS AND CONCLUSIONS: The analysis indicated that
      the lower the temperature, the slower the geographic dispersal of Ae. aegypti
      population. This factor predominantly influenced the macro regional dispersal
      patterns of the species in the state of Sao Paulo. There was no clear influence
      of temperature on the dispersal of Ae. albopictus. The influence of rainfall on
      dispersal patterns was seen only for Ae. aegypti in a state area. No influence
      was detected on the prior presence of Ae. albopictus on the establishment of Ae.
      aegypti.

PMID- 12045798
TI  - [Evaluation of the temperature influence on the development of Aedes albopictus].
AB  - OBJECTIVE: To verify the temperature's influence on the Aedes albopictus
      development stages under laboratory conditions. METHODS: The development period
      of eggs, larvae and pupas were assessed at constant temperatures, 15 degrees C,
      20 degrees C, 25 degrees C and 30 degrees C, inside acclimatized chambers with 70
      85% of relative humidity, and LD 12:12 h. The effect of the four constant
      temperatures was assessed using variance analysis. RESULTS: The incubation
      periods of eggs were 38.38, 19.09, 13.10, and 10.44 days. Larval periods for
      males lasted 30.13, 13.83, 7.36, and 5.57 days; for females it lasted 33.22,
      15.00, 8.06, and 6.16 days. Pupil period for males lasted 8.01, 4.92, 2.40, and
      1.76 days; and for females it lasted 8.15, 5.11, 2.60, and 1.88 days under the
      temperatures of 15 degrees C, 20 degrees C, 25 degrees C and 30 degrees C,
      respectively. In all development stages for all temperatures, significant
      differences were found at the level of 5%. The development period was inversely
      associated to the temperature, and the larval period was shorter in males than in
      females. Under the temperatures of 20 degrees C and 30 degrees C, the development
      of immature stages was shorter and their viability was greater than at 15 degrees
      C. CONCLUSIONS: In the conditions the experiment was performed, the temperature
      affected significantly and inversely proportional Aedes albopictus immature
      stages. These results show that immature stages are more susceptible at low
      temperatures due to the longer time required completing their development. This
      could be used in vector control strategies.

PMID- 12045799
TI  - [Birthweight and caffeine consumption].
AB  - OBJECTIVES: To assess the association between maternal caffeine consumption
      during pregnancy and low birth weight, prematurity and intrauterine growth
      retardation. METHODS: A case-control was carried out and 354 newborns of single
      labor with birthweight <2,500 g (cases) and 354 with birthweight >3,000 g
      (controls) were analyzed. Caffeine consumption was calculated based on daily
      consumption of coffee, soft drinks and tea. Results were adjusted using multiple
      logistic regression for the following confounders: mother's age, schooling,
      income, marital status, skin color, parity, smoking, previous low birthweight
      children, mother's pre-pregnancy weight, employment status, interval between
      pregnancies, prenatal care and high blood pressure. RESULTS: For caffeine
      consumption <300 mg/day and >300 mg/day, the adjusted odds ratios for low
      birthweight were: 0.72 (95%IC=0.45-1.25) and 0.47 (95%IC=0.24-0.92); prematurity:
      0.59 (95%IC=0.32-1.09) and 0.32 (95%IC=0.15-0.72); and intrauterine growth
      retardation: 1.16 (95%IC=0.45-3.01) and 0.64 (95%IC=0.20-1.98), respectively.
      CONCLUSION: There was no association between caffeine consumption during
      pregnancy and low birthweight, prematurity and intrauterine growth retardation.

PMID- 12045800
TI  - [Mother's ability of childcare and children malnutrition].
AB  - OBJECTIVES: To identify and measure the risk of malnutrition associated to
      determining indicators of mother's ability of childcare: familial structure,
      education level, work, maternal physical and mental health. METHODS: A case
      control study was performed. Cases (101 children whose weight/age was below 5th
      percentile) and controls (200 children whose weight/age was above 25th
      percentile) were selected using anthropometric surveys during three vaccination
      campaigns in 1996 and 1997. Data was collected by interviewing the children's
      mothers at home. To detect the net effect of each factor studied, multivariate
      hierarchical analyses were carried out. The factors investigated and possible
      control variables were grouped in blocks, arranged according to order they
      affected the child's nutritional status. In order to identify the control
      variables a p<0.20 (univariate analyses) was assumed and to identify associations
      between a given factor and malnutrition a p<0.05 was assumed. RESULTS:
      Malnutrition risk factors identified are: (a) adverse familial structure,
      indicated by single parenting (OR=2.2; 95%CI, 1.1-4.5); (b) hospitalization of
      the mother during pregnancy (OR=3.5; 95%CI, 1.6-7.7); (c) mother's poor mental
      health, determined by the presence of 3 to 4 symptoms of depression included in
      the SRQ-20 (OR=3.1; 95%CI, 0.9-10.3); and (d) family stress factors, suggestive
      signs of alcoholism in at least one family member (OR=2.1; 95%CI, 1.2-3.9). In
      addition to these factors, child's age at the time the mother resumed/started
      working was also independently associated to malnutrition. However, it produced
      mixed effects: for children aged 4 to 12 months, the mothers' resuming work
      resulted in a protection factor whereas their resuming later tended to increase
      the risk of malnutrition. CONCLUSIONS: It was evidenced that the factors that
      define the mother's ability of child care affect the child's nutritional status.

PMID- 12045801
TI  - [Waist-to-hip ratio and dietary factors in adults].
AB  - OBJECTIVES: To assess the association between diet factors and abdominal fat
      accumulation. METHODS: A household survey carried out in the city of Rio de
      Janeiro during 1995-1996. The usual diet of a sample of 2,441 individuals (42.8%
      men and 57.2% women), aged 20 to 60 years, was investigated using a food
      frequency questionnaire and data about height, weight, waist and hip perimeter
      was collected. The cut-off points for inadequate waist-to-hip ratio (WHR) for men
      and women were 0.95 and 0.80, respectively. RESULTS: Inadequate WHR was
      positively associated with age, cigarette smoking, body mass index, and inversely
      associated with education level, income and leisure physical activity in both men
      and women (p<0.05). Inadequate WHR was not associated with lipids, carbohydrates
      and total fiber intake. Positive association was found with inadequate WHR and
      spirits consumption among menopause women (p<0.001), and the consumption of four
      or more glasses of beer per day in men (p<0.001). CONCLUSION: In agreement with
      other studies, alcohol intake was associated with abdominal fat accumulation.

PMID- 12045802
TI  - [Prevalence of drug use during pregnancy: a pharmacoepidemiological approach].
AB  - INTRODUCTION: Few Brazilian papers on the use of medication in pregnancy have
      been found in the indexed medical literature. This paper describes the use of
      medication during pregnancy among women who gave birth in a teaching maternity
      hospital in the city of Campinas, Brazil. METHODS: A retrospective study on the
      pattern of drug use during pregnancy was conducted among 1,000 mothers who were
      interviewed using a structured questionnaire after delivery, while they were
      still in hospital. The following parameters were registered: sociodemographic
      characteristics, obstetric and contraceptive history, data on prenatal care and
      medications used during pregnancy. Statistical analysis was performed using ANOVA
      and chi-square test at p = 0.05. RESULTS: Among the interviewed patients, 94.6%
      had taken at least one medication during pregnancy, and 46.1% had used medication
      in the first trimester. Of 3,778 medications reported, 88.8% had been prescribed
      by a doctor. The median of medications taken was 3 (ranging from 0 to 18). The
      six most used classes of medications were: analgesics, spasmolytics,
      gynecological antiinfectious agents, antianemics, antacids and systemic
      antibiotics. The five most used medications were: butyl scopolamine, ferrous
      sulfate, dipirone, nistatin and multivitamin tablets. Only 27.7% of the patients
      had been alerted to the risk of taking medication during pregnancy. CONCLUSION:
      Knowing the profile of medications used during pregnancy may help devising
      programs to provide information to the patients and continuing education to
      health care professionals.

PMID- 12045803
TI  - [Living conditions and occupational organization associated with common mental
      disorders].
AB  - OBJECTIVE: To determine the prevalence of common mental disorders (CMD) and
      evaluate their association with living conditions and occupational organization.
      METHODS: A cross-sectional survey of a random sample of private households was
      carried out in Olinda, Brazil, in 1993. The sample consisted of 621 adults aged
      15 years or over and the participants were interviewed using the Self-Reporting
      Questionnaire (SRQ-20) and a second questionnaire on social and economic
      characteristics. Crude and adjusted odds ratios were estimated using logistic
      regression analysis. RESULTS: The overall prevalence of CMD was 35%. Only the
      variables education level (p<0.0001) and housing conditions (p=0.02) showed an
      independent association with CMD after adjustment for other living conditions
      variables, sex, age and marital status. Regarding occupational organization, non
      regulated blue-collar workers (OR=2.21; 95% CI 1.1-4.5) and subjects with the
      lowest per capita monthly household income (OR=2.87; 95%CI 1.4-5.8) showed a
      higher prevalence of CMD. CONCLUSIONS: Lower education level and income,
      exclusion from the law regulated labor market, and social class structure produce
      stressful situations increasing CMD.

PMID- 12045804
TI  - Assessment of a consultation-liaison psychiatry and psychology health care
      program.
AB  - OBJECTIVE: To investigate the relevance of subjective criteria adopted by a
      psychiatry and psychology consultation-liaison service, and their suitability in
      the evaluation of case registries and objective results. METHODS: Semi-structured
      interviews were conducted and all supervisors of the university hospital service
      were interviewed. Routinely collected case registries were also reviewed.
      Standardized assessment with content analysis for each category was carried out.
      RESULTS: The results showed distortions in the adopted service focus (doctor
      patient relationship) and consultant requests. This focus is more on consulting
      physician-oriented interventions than on patients. DISCUSSION: Evaluation of the
      relevance of service criteria could help promoting quality assessment of the
      services provided, mainly when objective criteria have not yet been established
      to assure their suitability.

PMID- 12045805
TI  - [Differences between normative criteria and self-perception in the assessment of
      malocclusion].
AB  - OBJECTIVE: To evaluate the impact of objectively defined orthodontic needs
      (normative criteria) on the external aspect and mastigation's satisfaction, and
      to compare these needs to self-perceived ones (subjective criteria) among
      adolescents. METHODS: A cross-sectional study was carried out among all 315
      students aged 14-18 years who attended a highschool in Florianopolis, Brazil. A
      single dentist collected clinical data about malocclusion (Dental Aesthetic
      Index) and a questionnaire was applied to assess perceived aesthetic and
      masticatory satisfaction and need for orthodontic treatment. Data analysis
      included frequency distribution calculation and multiple logistic regression
      modeling. RESULTS: There were high participation of 95% (n=300) and intra
      examiner agreement (Kappa 0.6-1.0). The prevalence of one form of malocclusion
      was 71.3%. Crowding in one or two incisal segments [OR=2.8 (1.6-4.9)] and overjet
      [OR=2,4 (1.4-4.3)] were risk factors associated with perceived aesthetic
      dissatisfaction. Adolescents who had anterior mandibular irregularity [OR=3.3
      (1.6-6.9)], overjet [OR=1.7 (1.1-3.0)] and anterior diastema [OR=3.1 (1.4-6.9)]
      revealed the highest self-perceived need for orthodontic treatment. CONCLUSIONS:
      There are different degrees of objectively defined occlusal problems acceptable
      in the population which interfere with their decision to seek treatment and have
      a direct impact on the need of care. Subjective measures should be incorporated
      to clinical criteria currently used.

PMID- 12045806
TI  - [Bambui Project: an evaluation of private, public and unionized dental services].
AB  - OBJECTIVE: Since one of the goals of dental services is to reduce the effects of
      social inequality on dental health, it was assessed whether there are
      inequalities among those seeking dental care from private, public and unionized
      services. METHODS: The study population consisted of adults aged 18 years or more
      living in the city of Bambui, Brazil. Participants were interviewed using a
      structured questionnaire. Data analysis was carried out using Pearson's chi
      square test, odds ratio and 95% confidence intervals (Woolf's method). RESULTS:
      There were included 656 subjects who met the study's inclusion criteria. Adjusted
      results using multiple logistic regression showed that those using private
      services were more likely to be satisfied with their teeth's looks (OR=3.03;
      95%CI =1.70-5.39) and chewing ability (OR=2.27; 95%CI=1.17-4.40) compared to
      those using public services. Also, they were less likely to perceive their need
      for dental treatment (OR=0.39; 95%CI=0.18-0.86) and were more likely to have had
      restorative (OR=9.57; 95%CI=4.72 - 19.43) and/or preventive (OR=5.57; 95%CI=2.31 
      13.40) treatment in their last visit to the dentist's. Those using unionized
      services were more likely to have had restorative (OR=8.51; 95%CI=2.80 - 25.92)
      and/or preventive treatment (OR=11.42; 95%CI=3.49 - 37.43) in their last visit to
      the dentist's when compared to those using public services. However, there were
      no differences regarding satisfaction with their teeth's looks, chewing ability,
      and perceived treatment needs. CONCLUSION: Public dental care services have not
      been able to reduce social inequalities related to oral health care.

PMID- 12045807
TI  - [Presence of Aedes aegypti in Bromeliaceae and plant breeding places in Brazil].
AB  - The frequency of Bromeliaceae and other plant breeding places where Aedes aegypti
      can be found is reported during two consecutive operational cycles (focal
      treatment) in the city of Rio de Janeiro. These cycles took place from November
      12 2000 to March 9 2001 and from March 12 2001 to June 15 2001. This study
      concentrates on the epidemiological implications resulting from the growing use
      of these plants as decorative living objects.

PMID- 12045808
TI  - [First report of Aedes albopictus in the state of Santa Catarina, Brazil].
AB  - Three adult females of Aedes (Stegomyia) albopictus (Skuse) were captured using a
      human bait in the surrounding dwelling area of the remaining rain forest in
      Itaguassu beach, island of Sao Francisco do Sul, northern coast of the state of
      Santa Catarina, Brazil.

PMID- 12045809
TI  - [Finding of Hemencyrtus herbertii (Hymenoptera: Encyrtidae) parasite breeding in
      Musca domestica (Diptera: Muscidae) in Brazil].
AB  - This is the first report of the occurrence of Hemencyrtus herbertii (Hymenoptera:
      Encyrtidae) parasitizing pupae of Musca domestica (Diptera: Muscidae) in human
      feces in Brazil.

PMID- 12045810
TI  - [Use of vitamin supplements among university students in Sao Paulo, Brazil].
AB  - With the purpose of determining the prevalence of vitamin consumption, a survey
      was conducted in a sample of 894 private university freshmen in Sao Paulo. It
      revealed that 30.4% of the students consumed vitamin supplements within the
      preceding 3 months -23.1% on a regular basis and 6.0% sporadically. Vitamin C and
      multivitamin supplements were the most consumed products. The regular consumption
      of vitamin supplements was related to the frequency of physical exercises. "To
      stay healthy" was the most cited reason for supplementation.

PMID- 12045811
TI  - [Schistosoma mansoni: a study of pathogenesis of Santa Rosa strain (Campinas, SP,
      Brasil) in mice].
AB  - The present paper reports the comparison between a newly isolated strain of S.
      mansoni in the city of Campinas (SP, Brazil) named SR, with the strains BH (Belo
      Horizonte, MG, Brazil) and SJ (Sao Jose dos Campos, SP, Brazil). The study was
      done using mice experimentally infected with 70 cercariae from sympatric snails:
      B. glabrata for the BH strain and B. tenagophila for the SJ and SR strains. The
      data obtained revealed that the new strain is less pathogenic than the other two,
      since it yielded fewer worms and shed eggs, a lower number of granulomas and a
      smaller granuloma size in the liver and intestine.

PMID- 12045812
TI  - [Comparison between the modified Ziehl-Neelsen and Acid-Fast-Trichrome methods
      for fecal screening of Cryptosporidium parvum and Isospora belli].
AB  - Due to the importance of Cryptosporidium parvum, Cyclospora cayetanensis and
      Isospora belli as opportunistic parasites, it is essential for laboratories to
      morphologically differentiate these coccidia. Among the recommended methods for
      diagnosis of C. parvum and I. belli is the Modified Ziehl-Neelsen stain (MZN) and
      recently a new technique, the Acid-Fast-Trichrome (AFT) was proposed. The purpose
      of this study was to compare the AFT and MZN techniques regarding the detection
      of C. parvum and I. belli oocysts in stool samples of HIV-positive patients.
      According to the presence (n=60) or absence of diarrhea (n=60), two groups were
      selected for inclusion in this study. The stool samples were collected in 10%
      formalin solution and the pellets, obtained without and after centrifugation
      concentration (500xg; 10 min), were submitted to both stain techniques.
      Considering the positivity of the techniques (AFT and MZN), we observed the
      superiority of MZN stain (n=19; 100% positive cases) over AFT (n=8; 42.1%). The
      identification of the 101 truly-negative cases was possible with both techniques,
      but when the AFT stain was used, the oocysts showed a variable inner stain
      degree, which resulted in false-negatives. Enteric coccidiosis was more frequent
      among the patients who presented diarrhea (26.6%) compared to asymptomatic
      individuals (5%); C. cayetanensis was not detected in these groups. We were
      interested in evaluating the employment of AFT for the Cyclospora oocyst stain.
      Based on the sensitivity and specificity obtained in this study (100%), we
      concluded that the MZN technique is still the most indicated for routine use in
      clinical analysis laboratories, for the diagnosis of cryptosporidiosis and
      isosporosis, especially when it was used together with the centrifugation
      procedure (500xg; 10 min). Our results showed that with some improvements, AFT
      would be a simple and inexpensive technique appropriate for use in the diagnosis
      of intestinal coccidia (C. parvum, C. cayetanensis and I. belli). It can also be
      extended to the detection of microsporidia.

PMID- 12045814
TI  - Education in primary school as a strategy to control dengue.
AB  - The proliferation of Aedes aegypti, a species of mosquito that is the vector of
      the dengue pathogen, is being augmented by the population's lack of care in
      allowing the formation of larval habitats. One form of controlling dengue is the
      distribution of information on the mosquito to improve awareness and to provide
      the means necessary for the elimination of its reproductive habitats. To evaluate
      a teaching method concerning the vector and dengue, students from the 5th and 6th
      years of primary education were compared before and after didactic intervention
      with a group of control students. The students who received intervention were
      more successful in identifying the stages of the cycle, biological and
      morphological characteristics of the adult insect and the importance of the
      mosquito in health issues. The didactic intervention was successful in developing
      knowledge leading to increased awareness of the importance of preventative
      measures that should be taken against the vector and the disease.

PMID- 12045813
TI  - Toxoplasma antibody and stool parasites in public school children, Rolandia,
      Parana, Brazil.
AB  - The occurrence of toxoplasmosis and enteroparasitosis was studied in 434 children
      from elementary schools in the rural and urban areas of Rolandia, Parana State,
      Brazil. Sera and fecal samples from all the students were submitted to IFA for
      Toxoplasma gondii and coproparasitological tests, respectively. The children were
      tested by Amsler grid and 72 of them were examined for the presence of lesions
      compatible with ocular toxoplasmosis. Some variables were tested but none showed
      increased risk for toxoplasmosis. The distribution according to sex and age and
      also same other variables are presented and discussed. Correlations between
      Amsler's grid test, toxoplama RIFI, occurrence of eyes lesions and
      enteroparasitosis are also considered.

PMID- 12045815
TI  - [Space expansion of the American visceral leishmaniasis in Sao Luis, Maranhao,
      Brazil].
AB  - The space occupation and the expansion of American visceral leishmaniasis (AVL)
      were described in the municipality of Sao Luis, Maranhao, Northeast Brazil. AVL
      medical notes from the Fundacao Nacional de Saude as well as official documents
      about the space occupation were analyzed from September 1982 to December 1996.
      AVL cases were more likely to occur in recently settled suburbs and tended to
      follow the same spatial pattern observed for land occupations secondary to
      migratory fluxes.

PMID- 12045816
TI  - [Yanomami children's nutritional status in the middle Rio Negro, Brazilian
      Amazonia].
AB  - The nutritional status of 290 Yanomami Amerindians children, from birth to about
      six year-olds, living in the middle Rio Negro, Brazilian Amazonia, has been
      studied in 1998 and 1999 using the weight-for-height. All of them were of low
      stature. Twenty malnourished (7%), defined as below two standard deviations of
      NCHS' data, have been observed. Five of them showed a severe malnutrition (</= -3
      SD). Differences appeared between the communities, however without evident
      connection with the practices of these groups and their contacts with the
      outside. These data indicate a lack of scarcity in this population who preserves
      a traditional way of life and disposes of a large space for gathering and
      hunting. The cases of malnutrition are probably a conjoined consequence of
      infectious attacks in children and of a special bad status in their group.

PMID- 12045817
TI  - [Triatomine: ovicidal action of some pyretroids].
AB  - The insecticidal action on eggs of triatomine have been little considered in the
      control activitys of Chagas' disease. With objective [corrected] of to compare
      the potential of three synthetic pyrethroids (deltamethrin,alphacypermethrin and
      lambdacyhalothrin) on eggs, the authors realized laboratory tests. The pyretroid
      lambdacialotrin is more efficient. The following species were used in this
      experiment: Panstrongylus megistus and Triatoma sordida. The specie Triatoma
      sordida is more susceptible with the pyrethroids utilized.

PMID- 12045818
TI  - HTLV-I associated myelopathy in the northern region of Brazil (Belem-Para):
      serological and clinical features of three cases.
AB  - Three patients (males, black, ages 37, 40 and 57) attended a university clinic
      with a progressive paraparesis of obscure origin. One patient who referred
      disease duration of more than 16 years, showed diminished deep reflexes,
      bilateral Babinski's sign, diminished sensation of vibration, abnormal bladder
      function and back pain. The other two patients (with one and six years of disease
      duration) complained of weakness in one leg, increased deep reflexes and back
      pain. Babinski's sign and bladder disturbance were also present in the patient
      with six years of disease. Blood samples tested by an enzyme immune assay and a
      discriminatory Western blot were positive for HTLV-I. The familial analysis of
      one patient showed a possible pattern of sexual and vertical transmission of the
      virus. To the best of our knowledge, these are the first cases of a proven
      association between HTLV-I and TSP/HAM in Belem, Para, and emphasize the need to
      actively look for cases of neurological disease associated to the virus.

PMID- 12045819
TI  - [Hepatitis E].
AB  - Hepatitis E virus (HEV) is the second most frequent hepatotropic virus
      transmitted via fecal-oral route, following closely behind hepatitis A virus. The
      great epidemics of hepatitis described during the 50s and 60s, in India, were
      caused by this virus. Epidemic bursts have also been described in Central Africa,
      Latin America, Middle East and in the independent Republics of the ex-Soviet
      Union. The clinical features of the disease do not differ from those reported for
      other viral hepatitides. There have been no cases of chronic hepatitis E
      reported. Around 20% of women infected during pregnancy develop a severe form of
      hepatitis which courses to liver failure. Diagnosis of hepatitis is confirmed
      when antibodies (using ELISA) of the IgM class (acute phase) and/or IgG (infected
      and cured) are found in the serum. Immunoblot and PCR-RNA may be used as
      necessary. There is no specific treatment for hepatitis E. Hyperimmune serum has
      been tried by some authors. Prevention is achieved by following the habitual
      hygienic and dietetic recommendations valid for diseases transmitted by
      contaminated water. There is no effective vaccine against the disease.

PMID- 12045820
TI  - [Brucella spondylodiscitis: case report].
AB  - Vertebral localization of Brucellosis has a low occurrence nowadays. Because of
      its rarity, it is essential to pay attention to structural modifications of the
      vertebral segment caused by bacterial spondylodiscitis. Based on a clinical case,
      with radiological, anatomicopathological and labatorial aspects related to the
      diagnostic and also the treatment of this disease, the authors underscore the
      importance and serious consequences arising from a late diagnostic definition.

PMID- 12045821
TI  - Identification of Leishmania chagasi from skin in Leishmania/HIV co-infection: a
      case report.
AB  - A case of HIV/Leishmania co-infection presenting both visceral and cutaneous
      manifestations is reported. Leishmania infection was confirmed by conventional
      methods (parasitological approach and serology) and by PCR. Leishmania chagasi
      isolated from the skin lesion was characterized by enzyme electrophoresis and by
      restriction fragment length polymorphism of the internal transcribed spacer of
      the ribosomal gene.

PMID- 12045822
TI  - Software for pattern recognition of the larvae of Aedes aegypti and Aedes
      albopictus.
AB  - Software for pattern recognition of the larvae of mosquitoes Aedes aegypti and
      Aedes albopictus, biological vectors of dengue and yellow fever, has been
      developed. Rapid field identification of larva using a digital camera linked to a
      laptop computer equipped with this software may greatly help prevention
      campaigns.

PMID- 12045823
TI  - Tuberculosis-related middle ear otitis: a rare occurrence.

PMID- 12045824
TI  - [An AIDS patient with Trichoderma].

PMID- 12045825
TI  - [Osteomyelitis by Paracoccidioides brasiliensis].

PMID- 12045826
TI  - Reaction of diphenyl diselenide with hydrogen peroxide and inhibition of delta
      aminolevulinate dehydratase from rat liver and cucumber leaves.
AB  - The interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate
      dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2
      inhibited rat hepatic delta-ALA-D with an IC50 of 10 microM but not the enzyme
      from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increased the
      inhibitory potency of the original compound and the IC50 for animal delta-ALA-D
      inhibition was decreased from 10 to 2 microM. Delta-ALA-D from cucumber leaves
      was also inhibited by the products of reaction of (PhSe)2 with H2O2 with an IC50
      of 4 microM. The major product of reaction of (PhSe)2 with H2O2 was identified as
      seleninic acid and produced an intermediate with a (lambda)max at 265 nm after
      reaction with t-BuSH. These results suggest that the interaction of (PhSe)2 with
      mammal delta-ALA-D requires the presence of cysteinyl residues in close
      proximity. Two cysteine residues in spatial proximity have been recently
      described for the mammalian enzyme. Analysis of the primary structure of plant
      delta-ALA-D did not reveal an analogous site. In contrast to (PhSe)2, seleninic
      acid, as a result of the higher electrophilic nature of its selenium atom, may
      react with additional cysteinyl residue(s) in mammalian delta-ALA-D and also with
      cysteinyl residues from cucumber leaves located at a site distinct from that
      found at the B and A sites in mammals. Although the interaction of
      organochalcogens with H2O2 may have some antioxidant properties, the formation of
      seleninic acid as a product of this reaction may increase the toxicity of organic
      chalcogens such as (PhSe)2.

PMID- 12045827
TI  - Somaclonal variation: a morphogenetic and biochemical analysis of Mandevilla
      velutina cultured cells.
AB  - Cell cultures of Mandevilla velutina have proved to be an interesting production
      system for biomass and secondary metabolites able to inhibit the hypotensive
      activity of bradykinin, a nonapeptide generated in plasma during tissue trauma.
      The crude ethyl acetate extract of cultured cells contains about 31- to 79-fold
      more potent anti-bradykinin compounds (e.g., velutinol A) than that obtained with
      equivalent extracts of tubers. Somaclonal variation may be an explanation for the
      wide range of inhibitor activity found in the cell cultures. The heterogeneity
      concerning morphology, differentiation, carbon dissimilation, and velutinol A
      production in M. velutina cell cultures is reported. Cell cultures showed an
      asynchronous growth and cells in distinct developmental stages. Meristematic
      cells were found as the major type, with several morphological variations. Cell
      aggregates consisting only of meristematic cells, differentiated cells containing
      specialized cell structures such as functional chloroplasts (cytodifferentiation)
      and cells with embryogenetic characteristics were observed. The time course for
      sucrose metabolism indicated cell populations with significant differences in
      growth and metabolic rates, with the highest biomass-producing cell line showing
      a cell cycle 60% shorter and a metabolic rate 33.6% higher than the control (F2
      cell population). MALDI-TOF mass spectrometric analysis of velutinol A in
      selected cell lines demonstrated the existence of velutinol A producing and
      nonproducing somaclones. These results point to a high genetic heterogeneity in
      general and also in terms of secondary metabolite content.

PMID- 12045828
TI  - Genomics and X-ray microanalysis indicate that Ca2+ and thiols mediate the
      aggregation and adhesion of Xylella fastidiosa.
AB  - The availability of the genome sequence of the bacterial plant pathogen Xylella
      fastidiosa, the causal agent of citrus variegated chlorosis, is accelerating
      important investigations concerning its pathogenicity. Plant vessel occlusion is
      critical for symptom development. The objective of the present study was to
      search for information that would help to explain the adhesion of X. fastidiosa
      cells to the xylem. Scanning electron microscopy revealed that adhesion may occur
      without the fastidium gum, an exopolysaccharide produced by X. fastidiosa, and X
      ray microanalysis demonstrated the presence of elemental sulfur both in cells
      grown in vitro and in cells found inside plant vessels, indicating that the
      sulfur signal is generated by the pathogen surface. Calcium and magnesium peaks
      were detected in association with sulfur in occluded vessels. We propose an
      explanation for the adhesion and aggregation process. Thiol groups, maintained by
      the enzyme peptide methionine sulfoxide reductase, could be active on the surface
      of the bacteria and appear to promote cell-cell aggregation by forming disulfide
      bonds with thiol groups on the surface of adjacent cells. The enzyme methionine
      sulfoxide reductase has been shown to be an auxiliary component in the
      adhesiveness of some human pathogens. The negative charge conferred by the
      ionized thiol group could of itself constitute a mechanism of adhesion by
      allowing the formation of divalent cation bridges between the negatively charged
      bacteria and predominantly negatively charged xylem walls.

PMID- 12045829
TI  - Identification and characterization of the two-component NtrY/NtrX regulatory
      system in Azospirillum brasilense.
AB  - Two Azospirillum brasilense open reading frames (ORFs) exhibited homology with
      the two-component NtrY/NtrX regulatory system from Azorhizobium caulinodans.
      These A. brasilense ORFs, located downstream to the nifR3ntrBC operon, were
      isolated, sequenced and characterized. The present study suggests that ORF1 and
      ORF2 correspond to the A. brasilense ntrY and ntrX genes, respectively. The amino
      acid sequences of A. brasilense NtrY and NtrX proteins showed high similarity to
      sensor/kinase and regulatory proteins, respectively. Analysis of lacZ
      transcriptional fusions by the beta-galactosidase assay in Escherichia coli ntrC
      mutants showed that the NtrY/NtrX proteins failed to activate transcription of
      the nifA promoter of A. brasilense. The ntrYX operon complemented a nifR3ntrBC
      deletion mutant of A. brasilense for nitrate-dependent growth, suggesting a
      possible cross-talk between the NtrY/X and NtrB/C sensor/regulator pairs. Our
      data support the existence of another two-component regulatory system in A.
      brasilense, the NtrY/NtrX system, probably involved in the regulation of nitrate
      assimilation.

PMID- 12045830
TI  - Lung clearance of 99mTc-DTPA in systemic lupus erythematosus.
AB  - The early demonstration of lung involvement in systemic lupus erythematosus (SLE)
      patients is a difficult but important task. In the present study we attempted to
      identify abnormalities in pulmonary clearance of 99mTc-DTPA in SLE, correlating
      their clearance data with clinical findings and disease activity. Forty-six
      consecutive SLE patients with and without active disease (LACC score) and 30
      normal volunteers were studied. All subjects were submitted to pulmonary
      scintigraphy with 99mTc-DTPA to evaluate the pulmonary clearance, and to a chest
      X-ray, and SLE patients were submitted to tests of disease activity, spirometry,
      arterial blood gases and tests to assess acute-phase proteins. Pulmonary
      clearance was faster in SLE patients with active disease when compared to normal
      controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min
      (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of
      abnormal clearance rates in patients with active disease (11 of 26 patients,
      42.3%) when compared with SLE patients without disease activity (2 of 20
      patients, 10%) (P = 0.04). A significant correlation was observed between the
      clearance rates and cough (P<0.05), but not between the clearance rates and
      dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear
      antibody titers and patterns, C-reactive protein or anti-double stranded DNA
      antibodies. We conclude that the pulmonary clearance of 99mTc-DTPA is increased
      in SLE patients with active disease.

PMID- 12045831
TI  - Effect of calcium intake on urinary oxalate excretion in calcium stone-forming
      patients.
AB  - Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption
      of dietary oxalate that is bound by intestinal calcium. The aim of the present
      study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic
      patients under different calcium intake. Fifty patients (26 females and 24 males,
      41 +/- 10 years old), whose 4-day dietary records revealed a regular low calcium
      intake (<or=500 mg/day), received an oral calcium load (1 g/day) for 7 days. A 24
      h urine was obtained before and after load and according to the calciuria under
      both diets, patients were considered as normocalciuric (NC, N = 15), diet
      dependent hypercalciuric (DDHC, N = 9) or diet-independent hypercalciuric (DIHC,
      N = 26). On regular diet, mean oxaluria was 30 +/- 14 mg/24 h for all patients.
      The 7-day calcium load induced a significant decrease in mean oxaluria compared
      to the regular diet in NC and DIHC (20 +/- 12 vs 26 +/- 7 and 27 +/- 18 vs 32 +/-
      15 mg/24 h, respectively, P<0.05) but not in DDHC patients (22 +/- 10 vs 23 +/- 5
      mg/24 h). The lack of an oxalate decrease among DDHC patients after the calcium
      load might have been due to higher calcium absorption under higher calcium
      supply, with a consequent lower amount of calcium left in the intestine to bind
      with oxalate. These data suggest that a long-lasting regular calcium consumption
      <500 mg was not associated with high oxaluria and that a subpopulation of
      hypercalciuric patients who presented a higher intestinal calcium absorption
      (DDHC) tended to hyperabsorb oxalate as well, so that oxaluria did not change
      under different calcium intake.

PMID- 12045832
TI  - Esophageal striated muscle contractions in patients with Chagas' disease and
      idiopathic achalasia.
AB  - Chagas' disease causes degeneration and reduction of the number of intrinsic
      neurons of the esophageal myenteric plexus, with consequent absent or partial
      lower esophageal sphincter relaxation and loss of peristalsis in the esophageal
      body. The impairment of esophageal motility is seen mainly in the distal smooth
      muscle region. There is no study about esophageal striated muscle contractions in
      the disease. In 81 patients with heartburn (44 with esophagitis) taken as
      controls, 51 patients with Chagas' disease (21 with esophageal dilatation) and 18
      patients with idiopathic achalasia (11 with esophageal dilatation) we studied the
      amplitude, duration and area under the curve of esophageal proximal contractions.
      Using the manometric method and a continuous perfusion system we measured the
      esophageal striated muscle contractions 2 to 3 cm below the upper esophageal
      sphincter after swallows of a 5-ml bolus of water. There was no significant
      difference in striated muscle contractions between patients with heartburn and
      esophagitis and patients with heartburn without esophagitis. There was also no
      significant difference between patients with heartburn younger or older than 50
      years or between men and women or in esophageal striated muscle contractions
      between patients with heartburn and Chagas' disease. The esophageal proximal
      amplitude of contractions was lower in patients with idiopathic achalasia than in
      patients with heartburn. In patients with Chagas' disease there was no
      significant difference between patients with esophageal dilatation and patients
      with normal esophageal diameter. Esophageal striated muscle contractions in
      patients with Chagas' disease have the same amplitude and duration as seen in
      patients with heartburn. Patients with idiopathic achalasia have a lower
      amplitude of contraction than patients with heartburn.

PMID- 12045833
TI  - Cholinergic stimulation with pyridostigmine reduces the QTc interval in coronary
      artery disease.
AB  - Parasympathetic dysfunction is an independent risk factor in patients with
      coronary artery disease; thus, cholinergic stimulation is a potential therapeutic
      measure that may be protective by acting on ventricular repolarization. The
      purpose of the present study was to determine the effects of pyridostigmine
      bromide (PYR), a reversible anticholinesterase agent, on the electrocardiographic
      variables, particularly QTc interval, in patients with stable coronary artery
      disease. In a randomized double-blind crossover placebo-controlled study,
      simultaneous 12-lead electrocardiographic tracings were obtained at rest from 10
      patients with exercise-induced myocardial ischemia before and 2 h after the oral
      administration of 45 mg PYR or placebo. PYR increased the RR intervals (pre: 921
      +/- 27 ms vs post: 1127 +/- 37 ms; P<0.01) and, in contrast with placebo,
      decreased the QTc interval (pre: 401 +/- 3 ms vs post: 382 +/- 3 ms; P<0.01). No
      other electrocardiographic variables were modified (PR segment, QT interval, QT
      and QTc dispersions). Cholinergic stimulation with PYR caused bradycardia and
      reduced the QTc interval without important side effects in patients with coronary
      disease. These effects, if confirmed in studies over longer periods of
      administration, may suggest a cardioprotection by cholinergic stimulation with
      PYR.

PMID- 12045834
TI  - Impaired regeneration of dystrophin-deficient muscle fibers is caused by
      exhaustion of myogenic cells.
AB  - Duchenne muscular dystrophy is one of the most devastating myopathies. Muscle
      fibers undergo necrosis and lose their ability to regenerate, and this may be
      related to increased interstitial fibrosis or the exhaustion of satellite cells.
      In this study, we used mdx mice, an animal model of Duchenne muscular dystrophy,
      to assess whether muscle fibers lose their ability to regenerate after repeated
      cycles of degeneration-regeneration and to establish the role of interstitial
      fibrosis or exhaustion of satellite cells in this process. Repeated degenerative
      regenerative cycles were induced by the injection of bupivacaine (33 mg/kg), a
      myotoxic agent. Bupivacaine was injected weekly into the right tibialis anterior
      muscle of male, 8-week-old mdx (N = 20) and C57Bl/10 (control, N = 10) mice for
      20 and 50 weeks. Three weeks after the last injection, the mice were killed and
      the proportion of regenerated fibers was counted and reported as a fibrosis
      index. Twenty weekly bupivacaine injections did not change the ability of mdx
      muscle to regenerate. However, after 50 weekly bupivacaine injections, there was
      a significant decrease in the regenerative response. There was no correlation
      between the inability to regenerate and the increase in interstitial fibrosis.
      These results show that after prolonged repeated cycles of degeneration
      regeneration, mdx muscle loses its ability to regenerate because of the
      exhaustion of satellite cells, rather than because of an increase in interstitial
      fibrosis. This finding may be relevant to cell and gene therapy in the treatment
      of Duchenne muscular dystrophy.

PMID- 12045835
TI  - Induction of interleukin-10 by HIV antigens in peripheral mononuclear cells of
      health care workers after occupational exposure to HIV-1-positive blood.
AB  - Evaluation of HIV-induced IL-2 production by peripheral blood mononuclear cells
      (PBMC) and HIV-specific T helper and cytotoxic T lymphocyte (CTL) responses in
      health care workers (HCW) occupationally exposed to HIV reveals a high rate of
      response to HIV among non-seroconverters. IL-10 is also known to interfere with
      HIV infection in vitro. To evaluate the induction of IL-10 by HIV antigens in HCW
      occupationally exposed to HIV, 18 HCW with percutaneous injury were enrolled in
      this study, 9 of them exposed to HIV-contaminated blood, and 9 exposed to HIV
      negative blood. PBMC were incubated on plates coated with HIV-1 antigens, and IL
      10 was measured in supernatants by ELISA. Five of nine HCW exposed to HIV
      contaminated blood presented HIV-induced IL-10. Two of nine HCW exposed to HIV
      negative source patients also had detectable levels of HIV-induced IL-10, one of
      them in the sample obtained on the day of accidental exposure. There was a
      relationship between the type of device involved in injury and IL-10 production.
      Individuals exposed to hollow needles or scalpels presented HIV-induced IL-10,
      whereas those exposed to solid needles and to digital puncture did not,
      suggesting a relationship between infectious load and IL-10. Although
      occupational exposure to HIV leads to a low rate of seroconversion, these
      individuals can develop an antigen-specific immune response characterized in our
      study by induction of IL-10 in PBMC in vitro.

PMID- 12045836
TI  - Antithrombotic effect of Lonomia obliqua caterpillar bristle extract on
      experimental venous thrombosis.
AB  - The venom of Lonomia obliqua caterpillar may induce a hemorrhagic syndrome in
      humans, and blood incoagulability by afibrinogenemia when intravenously injected
      in laboratory animals. The possible antithrombotic and thrombolytic activities of
      L. obliqua caterpillar bristle extract (LOCBE) were evaluated in this study. The
      minimal intravenous dose of the extract necessary to induce afibrinogenemia and
      anticoagulation was 3.0 and 10.0 microg protein/kg body weight for rabbits and
      rats, respectively. In rabbits, this dose induced total blood incoagulability for
      at least 10 h and did not reduce the weight of preformed venous thrombi, in
      contrast to streptokinase (30,000 IU/kg). In rats, pretreatment with 5.0 and 10.0
      microg/kg LOCBE prevented the formation of thrombi induced by venous stasis or by
      injury to the venous endothelium. The dose of 5.0 microg/kg LOCBE did not modify
      blood coagulation assay parameters but increased bleeding time and decreased
      plasma factor XIII concentration. When the extract was administered to rats at
      the dose of 10.0 microg/kg, the blood was totally incoagulable for 6 h. These
      data show that LOCBE was effective in preventing experimental venous thrombosis
      in rats, justifying further studies using purified fractions of the extract to
      clarify the mechanisms of this effect.

PMID- 12045837
TI  - Antinociceptive activity of sulfated carbohydrates from the red algae
      Bryothamnion seaforthii (Turner) Kutz. and B. triquetrum (S.G. Gmel.) M. Howe.
AB  - We report the antinociceptive activity, determined by the writhing, formalin and
      hot-plate tests in mice, of crude (F0/60), lectin and carbohydrate fractions
      isolated by ammonium sulfate precipitation (0 to 60%) from Bryothamnion
      seaforthii and B. triquetrum, species of red algae. Not only fraction F0/60 but
      also lectins from both species significantly inhibited acetic acid-induced
      abdominal contractions after intraperitoneal or oral administrations. In the
      formalin test, lectins (1 and 5 mg/kg, ip, and 5 to 20 mg/kg, po) inhibited the
      1st and 2nd phases (5 and 20 min, respectively), but the effect occurred
      predominantly on the 2nd phase. The effects of the lectins were totally or
      partially reversed by naloxone (2 mg/kg, sc) in the 1st and 2nd phases,
      respectively. Experiments performed with lectins in the absence and presence of
      avidin (1 mg/kg, ip) and D-mannose (1 mg/kg, ip) showed that avidin did not
      interfere with the effect of B. seaforthii lectin but partially reversed the
      effect of B. triquetrum lectin. D-Mannose completely reversed the effects of both
      species. F0/60 fractions from both algae significantly increased the latency time
      in response to thermal stimuli, and naloxone reversed antinociception, indicating
      the involvement of the opioid system in both the peripheral and central effects
      of the fractions. In the writhing test, the carbohydrate fractions were the most
      active, inhibiting the contractions by 71 and 79% (B. triquetrum) and by 46 and
      69% (B. seaforthii) at doses of 1 and 5 mg/kg, ip, respectively. Sulfated
      carbohydrate fractions of B. seaforthii and B. triquetrum, containing only about
      5% protein as contaminants, are probably responsible for the antinociceptive
      effects of these red algae.

PMID- 12045838
TI  - Effect of suramin on myotoxicity of some crotalid snake venoms.
AB  - We investigated the protective effect of suramin, an enzyme inhibitor and an
      uncoupler of G protein from receptors, on the myotoxic activity in mice of
      different crotalid snake venoms (A.c. laticinctus, C.v. viridis, C.d. terrificus,
      B. jararacussu, B. moojeni, B. alternatus, B. jararaca, L. muta). Myotoxicity was
      evaluated in vivo by injecting im the venoms (0.5 or 1.0 mg/kg) dissolved in
      physiological saline solution (0.1 ml) and measuring plasma creatine kinase (CK)
      activity. Two experimental approaches were used in mice (N = 5 for each group).
      In protocol A, 1 mg of each venom was incubated with 1.0 mg suramin (15 min, 37
      degrees C, in vitro), and then injected im into the mice at a dose of 1.0 mg/kg
      (in vivo). In protocol B, venoms, 1.0 mg/kg, were injected im 15 min prior to
      suramin (1.0 mg/kg, iv). Before and 2 h after the im injection blood was
      collected by orbital puncture. Plasma was separated and stored at 4 degrees C for
      determination of CK activity using a diagnostic kit from Sigma. Preincubation of
      some venoms (C.v. viridis, A.c. laticinctus, C.d. terrificus and B. jararacussu)
      with suramin reduced (37-76%) the increase in plasma CK, except for B.
      alternatus, B. jararaca or L. muta venoms. Injection of suramin after the venom
      partially protected (34-51%) against the myotoxicity of B. jararacussu, A.c.
      laticinctus and C.d. terrificus venom, and did not protect against C.v. viridis,
      L. muta, B. moojeni, B. alternatus or B. jararaca venoms. These results show that
      suramin has an antimyotoxic effect against some, but not all the North and South
      American crotalid snake venoms studied here.

PMID- 12045839
TI  - The use of protein structure/activity relationships in the rational design of
      stable particulate delivery systems.
AB  - The recombinant heat shock protein (18 kDa-hsp) from Mycobacterium leprae was
      studied as a T-epitope model for vaccine development. We present a structural
      analysis of the stability of recombinant 18 kDa-hsp during different processing
      steps. Circular dichroism and ELISA were used to monitor protein structure after
      thermal stress, lyophilization and chemical modification. We observed that the 18
      kDa-hsp is extremely resistant to a wide range of temperatures (60% of activity
      is retained at 80 degrees C for 20 min). N-Acylation increased its ordered
      structure by 4% and decreased its beta-T1 structure by 2%. ELISA demonstrated
      that the native conformation of the 18 kDa-hsp was preserved after hydrophobic
      modification by acylation. The recombinant 18 kDa-hsp resists to a wide range of
      temperatures and chemical modifications without loss of its main characteristic,
      which is to be a source of T epitopes. This resistance is probably directly
      related to its lack of organization at the level of tertiary and secondary
      structures.

PMID- 12045840
TI  - Effect of the acupoints ST-36 (Zusanli) and SP-6 (Sanyinjiao) on intestinal
      myoelectric activity of Wistar rats.
AB  - Despite its ancient use as a therapeutic tool to treat several ailments,
      acupuncture still faces the challenge of scrutiny by Western science both in
      terms of its efficacy and in terms of the characterization of its effects and
      mechanisms of actions underlying these effects. We investigated under well
      controlled and carefully characterized conditions the influence of electrical
      stimulation of acupuncture points ST-36 (Zusanli) and SP-6 (Sanyinjiao) on the
      myoelectric activity of the small intestine of 38 adult male Wistar rats.
      Electrical recordings obtained by means of four electrodes chronically implanted
      in the small intestine were used to assess the effects of acupuncture
      (electroacupuncture stimulation set at 2 Hz, intermittent stimulation, 1 V, for
      30 min). Immobilization of the animals was associated with a consistent decrease
      (-8 +/- 7%) in the myoelectric activity of the small intestine as measured by
      means of the root mean square. Conversely, acupuncture was able to significantly
      increase (overshoot) this activity compared to baseline (+44 +/- 7%). In
      contrast, immobilized animals subjected to sham acupuncture had only modest
      (nonsignificant) increases in myoelectric activity (+9 +/- 6%). Using carefully
      controlled conditions we confirmed previous noncontrolled studies on the ability
      of acupuncture to alter intestinal motility. The characterization of the
      topographic and temporal profiles of the effects observed here represents a basis
      for future dissection of the physiological and pharmacological systems underlying
      these effects.

PMID- 12045841
TI  - Effects of aerobic exercise training on heart rate variability during wakefulness
      and sleep and cardiorespiratory responses of young and middle-aged healthy men.
AB  - The purpose of the present study was to evaluate the effects of aerobic physical
      training (APT) on heart rate variability (HRV) and cardiorespiratory responses at
      peak condition and ventilatory anaerobic threshold. Ten young (Y: median = 21
      years) and seven middle-aged (MA = 53 years) healthy sedentary men were studied.
      Dynamic exercise tests were performed on a cycloergometer using a continuous ramp
      protocol (12 to 20 W/min) until exhaustion. A dynamic 24-h electrocardiogram was
      analyzed by time (TD) (standard deviation of mean R-R intervals) and frequency
      domain (FD) methods. The power spectral components were expressed as absolute (a)
      and normalized units (nu) at low (LF) and high (HF) frequencies and as the LF/HF
      ratio. Control (C) condition: HRV in TD (Y: 108, MA: 96 ms; P<0.05) and FD - LFa,
      HFa - was significantly higher in young (1030; 2589 ms2/Hz) than in middle-aged
      men (357; 342 ms2/Hz) only during sleep (P<0.05); post-training effects: resting
      bradycardia (P<0.05) in the awake condition in both groups; VO2 increased for
      both groups at anaerobic threshold (P<0.05), and at peak condition only in young
      men; HRV in TD and FD (a and nu) was not significantly changed by training in
      either groups. The vagal predominance during sleep is reduced with aging. The
      resting bradycardia induced by short-term APT in both age groups suggests that
      this adaptation is much more related to intrinsic alterations in sinus node than
      in efferent vagal-sympathetic modulation. Furthermore, the greater alterations in
      VO2 than in HRV may be related to short-term APT.

PMID- 12045842
TI  - Prevalence of Chagas' disease in Mulungu do Morro northeastern Brazil.
AB  - OBJECTIVE: The aim of this paper is to describe the prevalence of T. Cruzi
      infection in patients of from Mulungu do Morro, a rural tropical region of
      Northeastern Brazil. METHODS: A cross-sectional study was performed. After
      randomly selecting samples of the population, and obtaining their consents,
      patients completed pretested epidemiological and clinical questionnaires. Serum
      samples from all patients were collected and screened for the presence of T.
      cruzi antibodies. RESULTS: Of 694 patients examined, 174 patients (25.1%) tested
      had a positive serology for Chagas' disease. Of the study population, 341
      patients were male with 27% Chagas' disease prevalence, without a statistical
      difference. Illiteracy was the only variable related to T. cruzi infection in our
      population. CONCLUSION: In conclusion, our study points to the high prevalence of
      Chagas' disease among patients in Mulungu do Morro, suggesting that this region
      has a high frequency of infection and probably active vectorial transmission.

PMID- 12045843
TI  - Friedreich's ataxia: cardiac evaluation of 25 patients with clinical diagnosis
      and literature review.
AB  - OBJECTIVE: Cardiac evaluation (clinical, electrocardiographic and
      echocardiographic) of 25 Brazilian patients with clinical diagnosis of
      Friedreich's ataxia (FA) related to the frequency and the size of GAA repeats
      (unstable expansion of trinucleotide repeats that results in the disease).
      METHODS: Clinical and cardiac study including electrocardiogram and
      echocardiogram of all patients and molecular analysis to detect the frequency and
      the size of GAA expansion, by polymerase chain reaction analysis. RESULTS:
      Homozygous GAA expansion was detected in 17 patients (68%) - all typical cases.
      In 8 (32%) cases (6 atypical and 2 typical), no GAA expansion was observed,
      therefore it was not considered Friedreich's ataxia. All patients with GAA
      expansion (100%) had electrocardiographic abnormalities, and only 25% of the
      cases without GAA expansion had some abnormality on this exam. However, only 6%
      of all patients revealed some signals/symptoms suggestive of cardiac involvement.
      CONCLUSION: A molecular analysis is essential to confirm the diagnosis of
      Friedreich's ataxia; however, an adequate cardiac evaluation, including an
      electrocardiogram, was extremely useful to better screening the patients which
      should perform these molecular analysis.

PMID- 12045844
TI  - Consequences of the prolonged waiting time for patient candidates for heart
      surgery.
AB  - OBJECTIVE: To assess mortality and the psychological repercussions of the
      prolonged waiting time for candidates for heart surgery. METHODS: From July 1999
      to May 2000, using a standardized questionnaire, we carried out standardized
      interviews and semi-structured psychological interviews with 484 patients with
      coronary heart disease, 121 patients with valvular heart diseases, and 100
      patients with congenital heart diseases. RESULTS: The coefficients of mortality
      (deaths per 100 patients/year) were as follows: patients with coronary heart
      disease, 5.6; patients with valvular heart diseases, 12.8; and patients with
      congenital heart diseases, 3.1 (p<0.0001). The survival curve was lower in
      patients with valvular heart diseases than in patients with coronary heart
      disease and congenital heart diseases (p<0.001). The accumulated probability of
      not undergoing surgery was higher in patients with valvular heart diseases than
      in the other patients (p<0.001), and, among the patients with valvular heart
      diseases, this probability was higher in females than in males (p<0.01). Several
      patients experienced intense anxiety and attributed their adaptive problems in
      the scope of love, professional, and social lives, to not undergoing surgery.
      CONCLUSION: Mortality was high, and even higher among the patients with valvular
      heart diseases, with negative psychological and social repercussions.

PMID- 12045845
TI  - Left ventricular diastolic function in essential hypertensive patients: influence
      of age and left ventricular geometry.
AB  - PURPOSE: To evaluate diastolic dysfunction (DD) in essential hypertension and the
      influence of age and cardiac geometry on this parameter. METHODS: Four hundred
      sixty essential hypertensive patients (HT) underwent Doppler echocardiography to
      obtain E/A wave ratio (E/A), atrial deceleration time (ADT), and isovolumetric
      relaxation time (IRT). All patients were grouped according to cardiac geometric
      patterns (NG - normal geometry; CR - concentric remodeling; CH- concentric
      hypertrophy; EH - eccentric hypertrophy) and to age (<40; 40 - 60; >60 years).
      One hundred six normotensives (NT) persons were also evaluated. RESULTS: A
      worsening of diastolic function in the HT compared with the NT, including HT with
      NG (E/A: NT - 1.38+/-0.03 vs HT - 1.27+/-0.02, p<0.01), was observed. A higher
      prevalence of DD occurred parallel to age and cardiac geometry also in the
      prehypertrophic groups (CR). Multiple regression analysis identified age as the
      most important predictor of DD (r2=0.30, p<0.01). CONCLUSION: DD was prevalent in
      this hypertensive population, being highly affected by age and less by heart
      structural parameters. DD is observed in incipient stages of hypertensive heart
      disease, and thus its early detection may help in the risk stratification of
      hypertensive patients.

PMID- 12045846
TI  - Prevalence of risk factors for coronary artery disease in the Brazilian State of
      Rio Grande do Sul.
AB  - OBJECTIVE: To determine the risk factors prevalence for coronary artery disease
      in the State of Rio Grande do Sul, Brazil and to identify their relation with the
      age bracket. METHODS: We carried out an observational, cross-sectional study of
      1,066 adults older than 20 years in the Brazilian State of Rio Grande do Sul. We
      investigated the risk factors: familial antecedents, systemic arterial
      hypertension, high levels of cholesterol and glycemia, overweight/obesity,
      smoking and sedentary lifestyle. A standardized questionnaire completed at the
      patients' dwellings by health agents were used; the data were stored in an EPI
      INFO software database. The results were expressed with a 95% confidence
      interval. RESULTS: The sample composition was of 51.8% females. The risk factors
      prevalences were: 1) sedentary lifestyle 71.3%; 2) familial antecedents: 57.3%;
      3) overweight/obesity (body mass index >25): 54.7%; 4) smokers: 33.9%; 5)
      hypertension: 31.6% (considering >140/90 mm Hg) and 14.4% (considering >160/95 mm
      Hg); 6) high glycemia (>126 mg/dL): 7%; 7) high cholesterol >240 mg/dL): 5.6%.
      CONCLUSION: The prevalence of the major risk factors for coronary artery disease
      in the Brazilian state of Rio Grande do Sul could be determined in a study that
      integrated public and private institutions.

PMID- 12045848
TI  - Block of the mitral-pulmonary isthmus during ablation of a single left-sided
      accessory pathway causing different patterns of retrograde atrial activation.
AB  - The case of a 16-year-old patient with atrioventricular tachycardia caused by a
      single left anterolateral accessory pathway is reported. When the patient
      underwent radiofrequency ablation, a lesion on the mitral annulus lateral wall
      produced changes in the retrograde atrial activation pattern determined by that
      pathway; changes ranged from a delay in depolarization of the annulus posterior
      portions to full left atrium counterclockwise activation. Such phenomena were
      probably caused by a block in the isthmus between the annulus and the lower left
      pulmonary vein ostium. This case illustrates the importance of the mitral
      pulmonary isthmus in the process of left atrium activation, an alert to changes
      induced by its unintentional block during accessory pathway ablation.

PMID- 12045847
TI  - Repair of an atherosclerotic coronary artery aneurysm by implantation of a
      coronary covered stent.
AB  - An atherosclerotic aneurysm of the right coronary artery complicated by a recent
      myocardial infarction was successfully treated with coronary artery stenting,
      using a device consisting of 2 stents with a layer of expandable
      polytetrafluorethylene (PTFE) placed between them. A follow-up angiograph 5
      months after the procedure showed sustained initial results.

PMID- 12045849
TI  - Glossopharyngeal neuralgia associated with cardiac syncope.
AB  - Glossopharyngeal neuralgia is an uncommon condition that has rarely been
      described in association with syncope. We report here 2 cases of glossopharyngeal
      neuralgia in elderly patients. Both were male and underwent temporary pacemaker
      insertion to prevent syncopal episodes. We discuss the clinical and surgical
      treatment of glossopharyngeal neuralgia, the role of cardiac stimulation, and the
      possible physiopathological mechanism of the associated cardiac disturbances.

PMID- 12045850
TI  - The effect of intraoperative bupivacaine administration on parenteral narcotic
      use after laparoscopic appendectomy.
AB  - BACKGROUND: Little is known about the effect that prophylactic administration of
      local anesthesia into surgical incisions has on pain and analgesic use after
      laparoscopic appendectomy. We examined how preemptive infiltration of a local
      anesthetic affected the use of parenteral narcotics after laparoscopic
      appendectomy. METHODS: We conducted a retrospective chart review of 60 patients
      who underwent a laparoscopic appendectomy from January 2000 to April 2001 at our
      institution. We studied the association between prophylactic bupivacaine
      analgesia and patterns of postoperative parenteral narcotic use. RESULTS: Of 46
      patients who received intraoperative bupivacaine, 24 (52%) required postoperative
      parenteral narcotics as compared with 12 (86%) of 14 patients who did not receive
      bupivacaine (risk difference, 34%; 95% confidence interval [CI], 10-51%; p =
      0.02). After adjustment for other factors, the patients who received prophylactic
      bupivacaine were much less likely to receive parenteral narcotics during their
      postoperative hospital stay than the patients who did not receive prophylactic
      bupivacaine (odds ratio, 0.2; 95% CI, 0.1-0.9; p = 0.03). Furthermore, the
      patients who received prophylactic bupivacaine required fewer doses (median
      number of doses, 0.5; interquartile range [IQR], 0-2) of parenteral narcotics
      postoperatively than those who did not receive bupivacaine (median, 2; IQR, 1-4;
      p value for comparison, 0.03). CONCLUSION: Intraoperative bupivacaine infiltrated
      locally into surgical wounds is associated with both a decreased need for
      postoperative parenteral narcotics and a reduced number of doses in patients who
      have undergone a laparoscopic appendectomy.

PMID- 12045852
TI  - Lateral laparoscopic port sites should all be closed: the incisional "spigelian"
      hernia.
AB  - Incisional hernias are a recognized complication of all abdominal surgery,
      including laparoscopic surgery. Although most cases of laparoscopic port
      incisional hernias are seen in the midline, particularly around the umbilicus,
      there are several reports of herniation at laterally placed ports. Accepted
      surgical practice is to close the deep fascial layers at midline laparoscopic
      ports. However, the deep layers at the lateral ports are not usually closed. Two
      near-identical cases are reported in which incisional hernias have developed at
      the site where laterally placed 10-mm ports have pierced the spigelian fascia.
      Hernia development at an iatrogenic defect in an area that is already potentially
      weak, and therefore prone to herniation, has implications for lateral 10-mm port
      site closure. The closure of the deep layers of all lateral laparoscopic ports is
      advocated, especially if the spigelian fascia is pierced.

PMID- 12045853
TI  - Laparoscopic enucleation of an insulinoma: advantages of using the curved
      laparoscopic coagulating shears.
AB  - Laparoscopic excision is a widely accepted and well-described approach to islet
      cell tumors of the pancreas. We report the case of a patient with biochemically
      proven insulinoma who underwent successful enucleation using the curved
      laparoscopic coagulating shears. We discuss the advantages of using laparoscopy
      to manage these tumors and the increased benefit of using the curved instrument
      for this type of procedure.

PMID- 12045854
TI  - Emergency laparoscopic splenectomy for "wandering" (pelvic) spleen: case report
      and review of the literature on laparoscopic approach to splenic diseases.
AB  - Wandering spleen (WS) is a rare condition where the spleen, free from its
      ligaments, is allowed to move inside the abdomen predisposing the patient to life
      threatening complications due to torsion of the vascular pedicle; splenic
      infarction, portal hypertension, bleeding and acute abdomen may occur. WS is
      rarely suspected at presentation since symptoms are usually not specific and
      definitive diagnosis is usually reached only by imaging technologies such as
      color flow ultrasonography and angio-spiral computer tomography. A 42-year-old
      woman was referred to our institute from the Emergency and Accident ward,
      complaining of a sudden onset of sharp abdominal pain together with nausea and
      vomiting. At examination a large, painful mass was present on the left middle
      lower abdominal quadrant. A pelvic spleen was revealed at abdominal
      ultrasonography (US) and confirmed by abdominal CT. Emergency laparoscopy was
      carried out. The spleen was barely attached to the peritoneum of the anterior
      abdominal wall, covered by the greater omentum, the small bowel, and the
      transverse colon. Once mobilization of the spleen was concluded, the vascular
      pedicle appeared torted and thrombosed and laparoscopic splenectomy was
      performed. The patient was discharged on the 4th postoperative day with no
      complications. To date, only 5 cases of laparoscopic approach to WS have been
      reported. A review of the literature confirms that the reduction of postoperative
      stay, wound complications, and overall morbidity and a faster return to normal
      activity make laparoscopy the "gold standard" approach to the spleen as for
      treatment of many hematological disorders or more unusual splenic diseases.

PMID- 12045855
TI  - Scientific data from clinical trials: investigators' responsibilities and rights.

PMID- 12045856
TI  - Laparoscopic adrenalectomy for pheochromocytoma.
AB  - aparoscopic adrenalectomy is the standard for most surgical adrenal diseases. The
      aim of this study was to evaluate the safety and effectiveness of laparoscopic
      adrenalectomy for patients with pheochromocytoma. The medical records of 39
      consecutive patients who underwent laparoscopic adrenalectomy for
      pheochromocytomas from 1994 to 2000 at the University of California-San Francisco
      were reviewed. Three groups of patients were identified. The first group
      comprised 17 patients with classic symptoms and signs of pheochromocytoma. The
      second group comprised 17 patients who had minimal symptoms and incidentally
      discovered pheochromocytoma (i.e., "incidentaloma"), almost half of whom
      inappropriately underwent fine-needle biopsies before diagnosis. The third group
      consisted of 5 patients who had acute hypertensive crises and required intensive
      preoperative preparation. The mean age of the 22 men and 17 women was 46 years
      (range 20-84 years), and the mean adrenal tumor size was 4.8 cm (range 2-12 cm).
      A total of 43 laparoscopic adrenalectomies were performed for 35 patients with
      unilateral tumors and 4 patients with bilateral tumors. The retroperitoneal
      approach was used in four patients and the lateral transabdominal approach in the
      remaining patients without conversion to an open operation. There were no
      intraoperative complications or mortality. The mean duration of hospitalization
      was 1.7 days. In conclusion, patients with pheochromocytoma have a wide spectrum
      of presentations, from minimal symptoms to hypertensive crises. When evaluating
      an incidentaloma, pheochromocytoma should be excluded by metabolic testing, not
      by needle biopsy. Laparoscopic adrenalectomy is the preferred surgical approach
      for patients with pheochromocytoma because it is safe and efficacious.

PMID- 12045857
TI  - Loss of heterozygosity on the short arm of chromosome 1 in pheochromocytoma and
      abdominal paraganglioma.
AB  - Pheochromocytomas and abdominal paragangliomas are catecholamine-producing tumors
      that arise from sympathetic paraganglia within and outside the adrenal medulla,
      respectively. Deletions of the short arm of chromosome 1 have been implicated as
      important genetic events in their tumorigenesis and suggest a common genetic
      etiology. The aim of this study was to define further the chromosomal regions on
      1p that are involved in the development of these tumor types. We analyzed 46
      pheochromocytomas (1 benign, 6 malignant, 9 hereditary) and 7 paragangliomas (3
      benign, 4 malignant) from 50 patients for loss of heterozygosity (LOH) on 1p by
      genotyping 15 microsatellite markers spread over the chromosome arm. Overall, LOH
      was detected in 33 of 46 pheochromocytomas (72%) and in 6 of 7 (86%)
      paragangliomas. Three minimal regions of overlapping deletions were identified:
      one telomeric of D1S1612(1p36.2-pter), one centromeric of D1S429 (1cen-p13), and
      one in the 18 cM interval defined by D1S2134 andD1S1669 (1p32). The latter region
      harbors the leukocyte common antigen-related (LAR) gene, which shows altered
      expression in sporadic rat pheochromocytomas. In conclusion, chromosome 1p may be
      the site of at least three putative tumor-suppressor gene loci involved in the
      tumorigenesis of pheochromocytomas and abdominal paragangliomas. Further studies
      of these regions and of LARas a candidate gene would be valuable.

PMID- 12045858
TI  - Endoscopic treatment of solitary, bilateral, multiple, and recurrent
      pheochromocytomas and paragangliomas.
AB  - Because of extensive intraoperative catecholamine release, extreme
      vascularization, and demanding localization, laparoscopic and
      retroperitoneoscopic excision of pheochromocytomas and retroperitoneal
      paragangliomas is challenging. In a prospective clinical study, 61 chromaffin
      neoplasms (52 pheochromocytomas, 9 paragangliomas) were removed endoscopically
      from 52 patients (30 males, 22 females; age 44.4 +/- 16.3 years) at 55
      operations. Six patients showed multiple (two to five) tumors. Tumor size ranged
      from 1 to 7 cm (mean 3.6 +/- 1.4 cm). Twelve patients suffered from hereditary
      diseases. Seven patients had bilateral adrenal diseases; in three patients
      pheochromocytomas were removed on both sides synchronously. Four neoplasias were
      local recurrences (three pheochromocytomas, one paraganglioma). The laparoscopic
      route was chosen for six operations, and the retroperitoneoscopic technique was
      performed in 49 procedures. Partial adrenalectomy was performed in 19 operations
      (in all patients with bilateral diseases). High-dosage a-blockage with
      phenoxybenzamine was routinely used. There were no conversions to open surgery.
      Perioperative complications were minor (23%), and mortality was zero. The
      operating time for unilateral pheochromocytomas was 116 +/- 52 minutes (range 35
      285 minutes) and depended on tumor size (<3 cm vs. > or = 3 cm; p <0.01), gender
      (p <0.01), and extent of resection (partial vs. complete; p <0.05). The operating
      time for bilateral pheochromocytomas ranged from 285 to 385 minutes, and it was
      75 to 600 minutes for paragangliomas. Blood loss was 100 +/- 171 ml. Consumption
      of analgesics was low (mean 7 mg piritramide postoperatively). The median
      duration of postoperative hospitalization was 4 days. In six of seven patients
      with bilateral disease complete preservation of cortical function was achieved.
      Locoregional metastatic recurrence was found in one patient 3 years after
      retroperitoneoscopic adrenalectomy. Endoscopic removal of solitary, bilateral,
      multiple, and recurrent pheochromocytomas and retroperitoneal paragangliomas is
      feasible and safe but requires extensive experience in minimally invasive and
      endocrine surgery.

PMID- 12045859
TI  - Results of laparoscopic adrenalectomy for large and potentially malignant tumors.
AB  - Endoscopic adrenalectomy is the procedure of choice for patients with small
      functioning adrenal tumors. For most surgeons invasive adrenal carcinoma is an
      absolute contraindication for laparoscopic adrenalectomy (LA). Whether LA should
      be proposed for large (> 6 cm), potentially malignant tumors is questionable. The
      aim of this study was to evaluate the risks and outcome of LA performed in our
      department in patients with tumors > 6 cm and potentially malignant. We performed
      a retrospective study of 216 patients who underwent 233 LAs in our department
      from 1994 to 2000. We selected 19 patients with a tumor > 6 cm and potentially
      malignant: 8 nonfunctional tumors, 4 cortisol-secreting tumors, 1 virilizing
      tumor, and 6 pheochromocytomas. In none of these patients did preoperative
      investigations demonstrated invasive carcinoma. The median tumor size was 70 mm.
      LA was performed by a transperitoneal flank approach. Conversion to open
      adrenalectomy was performed in two patients owing to intraoperative evidence of
      invasive carcinoma. The median operating time was 150 minutes (range 95-240
      minutes). Capsular disruption occurred during the dissection of two
      pheochromocytomas. There was no postoperative morbidity. Six patients had an
      adrenocortical carcinoma on pathologic diagnosis: three of the eight
      nonfunctional tumors, one of the four cortisol-secreting tumors, and one
      virilizing tumor. One patient presented with liver metastases 6 months after
      surgery and died. The five other patients are disease-free with a follow-up
      ranging from 8 to 83 months. The 13 patients with benign lesions (6 cortical
      adenomas, 1 ganglioneuroma, 6 pheochromocytomas) are disease-free with a median
      follow-up of 47 months (range 10-81 months). In experienced hands LA can be
      proposed for large, potentially malignant tumors. Conversion to open
      adrenalectomy should be performed if local invasion is observed during surgery.
      At present the risk of intraabdominal recurrence is unknown.

PMID- 12045860
TI  - Importance of lymph node metastases in follicular thyroid cancer.
AB  - There are many concepts of risk and prognostic factor analysis for differentiated
      thyroid cancer. The prognostic role of lymph node metastases in follicular
      thyroid cancer (FTC), however, is still controversial. We performed a
      retrospective trial in 186 patients with FTC (124 women, 62 men; mean follow-up
      5.5 years) questioning whether lymph node metastases and radical thyroid surgery
      with neck dissection contribute to the prognosis of FTC. Univariate analysis
      demonstrated that lymph node metastasesp <0.005), tumor size (p <0.005), tumor
      stage (p <0.005), distant metastases p = 0.0063), and gender (p = 0.003) are
      significant prognostic factors for recurrence (Kaplan-Meier). Tumor size (p =
      0.004), lymph node metastases p = 0.0478), and distant metastases p = 0.0064)
      influenced mortality. Age and extent of surgery were not significant for
      recurrence nor was gender for mortality. Multivariate analysis (Cox regression
      test) characterized tumor size (p <0.005) and lymph node metastases p = 0.004) as
      prognostic factors for recurrence of FTC. No significant difference was detected
      between patients being treated by thyroidectomy when compared to patients treated
      by thyroidectomy plus neck dissection in relation to recurrence. Our data
      demonstrate lymph node metastases to be a significant prognostic factor for
      recurrence of FTC and the patient's survival. We advocate thyroidectomy plus
      central lymph node dissection as the basic surgical strategy. For T3 and T4
      tumors, unilateral modified neck dissection is an all but optional procedure.
      Whether radical surgery with thyroidectomy plus neck dissection has an impact on
      survival remains questionable.

PMID- 12045861
TI  - Complications of neck dissection for thyroid cancer.
AB  - Prophylactic and therapeutic neck dissections are used to control or eliminate
      local nodal disease in patients with thyroid cancer. The purpose of this study
      was to evaluate the results and complications of neck dissection. From 1992 to
      1999 a series of 115 consecutive neck dissections were performed in 74 patients
      (32 men, 42 women; mean age 48 years) with thyroid cancer and nodal metastases.
      Operations included central compartment, lateral modified, and suprahyoid
      dissection with and without total or completion thyroidectomy. Sixty-four percent
      of the patients had papillary, 4% follicular, and 32% medullary thyroid cancer.
      Complications included transient hypocalcemia (23%) defined by a postoperative
      serum calcium level of <2.0 mmol/L (8.0 mg/dl), one neck hematoma (0.9%), and one
      cardiac death (0.9%). There were no permanent recurrent nerve palsies.
      Hypocalcemia occurred more frequently when neck dissection was combined with
      total thyroidectomy than without it (p <0.005). In this group, the incidence of
      hypocalcemia was higher after central, than lateral, neck dissection. When neck
      dissection was performed without thyroidectomy, there was no difference in the
      rates of hypocalcemia between central, lateral, or central with lateral neck
      dissection (p = NS). Hypocalcemia did not increase with repeated neck dissections
      (p = NS). Permanent hypoparathyroidism occurred in 0.9%. There were no
      complications after suprahyoid dissection. The median duration of hospitalization
      was 1 day. Therapeutic neck dissection or repeated neck dissection can be
      performed relatively safely in patients with thyroid cancer. Hypocalcemia occurs
      most frequently when neck dissection is combined with total thyroidectomy.

PMID- 12045862
TI  - Diversification of minimally invasive parathyroidectomy for primary
      hyperparathyroidism: minimally invasive video-assisted parathyroidectomy and
      minimally invasive open videoscopically magnified parathyroidectomy with local
      anesthesia.
AB  - With the expansion of minimally invasive parathyroid surgery for primary
      hyperparathyroidism, new approaches and techniques evolved, creating new surgical
      algorithms with consequences for indication for surgery and patient selection.
      The presented methods of selective, minimally invasive parathyroidectomy
      represent this development of diversification. Minimally invasive video-assisted
      parathyroidectomy (MIVAP) has advanced to bilateral exploration, avoiding
      preoperative localization other than ultrasonography. Furthermore, a new
      technique of minimally invasive open parathyroidectomy with the option of
      videoscopic magnification under local anesthesia (MIPLA) for localizable adenomas
      is introduced. A series of 103 patients were operated on for primary
      hyperparathyroidism using minimally invasive procedures: 87 with MIVAP and 16
      with MIPLA. With MIVAP the conversion rate to cervicotomy for multiglandular
      disease or technical difficulties was 16% (n = 14). With MIPLA, conversion to
      general intubation anesthesia or additional sedation was necessary in four
      patients. A transient laryngeal nerve palsy was observed in one patient with
      MIVAP. Bilateral exploration was carried out during 29 MIVAPs and 2 MIPLAs. The
      duration of surgery differed, with a median 63 minutes for MIVAP and 39 minutes
      for MIPLA. Surgery under local anesthesia was completed in 4 patients with MIVAP
      and in 14 with MIPLA. All patients were cured of primary hyperparathyroidism.
      Preliminary results of diversified procedures demonstrate effects regarding
      omission of preoperative diagnostics, overall cost reduction, and increasing
      patient selection for selective parathyroid surgery because of primary
      hyperparathyroidism.

PMID- 12045863
TI  - Primary hyperparathyroidism revisited in menopausal women with serum calcium in
      the upper normal range at population-based screening 8 years ago.
AB  - Population-based screening showed 2.1% prevalence of primary hyperparathyroidism
      (pHPT) in postmenopausal women. Individuals with total serum (s)-calcium levels
      of 2.55 mmol/L or more at screening were diagnosed with pHPT when subsequent
      analysis supported inappropriately elevated intact parathormone (PTH) levels in
      relation to even normal s-calcium levels. The arbitrary diagnostic criteria were
      validated by parathyroidectomy. Herein we reinvestigated biochemical signs of
      pHPT in women not diagnosed with pHPT due to s-calcium 2.50 to 2.54 mmol/L (group
      A, n = 160) at screening or due to appropriate PTH levels on two occasions after
      screening (group B, n = 70). Altogether, 99 women in group A and 47 in group B
      underwent reinvestigation 8.8 years after screening when they were 65 to 84 years
      old. The s-calcium levels averaged 2.56 mmol/L and had increased in group A (mean
      0.04 mmol/L) and decreased in group B (mean 0.05 mmol/L). A total of 48 and 18
      females (48%, 38%), respectively, met the previously validated criteria of pHPT.
      Altogether 21% of them were hypercalcemic (range 2.60-3.12 mmol/L). Subgroup
      analysis showed that PTH had not increased with time (n = 47) and that
      atherogenic blood lipids, but not glucose levels, were similar in pHPT patients
      and matched controls (n = 37). Assuming the existence of pHPT already at
      screening, the prevalence of pHPT could be adjusted to 3.4%. Even the most
      liberal diagnostic criteria utilized at pHPT screening seemed to underdiagnose
      the disease by inefficient cutoff limits for s-calcium and PTH. Because one-fifth
      of the women with pHPT progressed to hypercalcemia, long-term follow-up is
      advocated for those with s-calcium in the upper normal range.

PMID- 12045864
TI  - Current national health insurance policies for thyroid cancer prophylactic
      surgery in the United States.
AB  - The efficacy of prophylactic thyroidectomy in patients with positive RET
      mutational analysis, familial thyroid cancer, or both has been reported. As cost
      has become critical to medical decision-making, this study was designed to
      evaluate currently existing coverage policies for prophylactic thyroidectomy. A
      confidential detailed cross-sectional nationwide survey of 481 medical directors
      from the American Association of Health Plans, Medicare, and Medicaid was
      conducted. Of the 150 respondents, 65% (n = 97) had 100,000 or more enrolled
      members, and 35% (n = 53) had fewer than 100,000 enrolled members. Only 9% of
      private plans have specific policies for coverage of prophylactic thyroidectomy
      for patients with a strong family history of thyroid cancer, 19% provided no
      coverage, and 72% had no policy. Only 9% of private plans have specific policies
      for patients with a known thyroid cancer genetic mutation, 12% provided no
      coverage, and 79% had no policy. Governmental carriers were less likely to
      provide coverage for prophylactic surgery: 4% for a strong family history and 6%
      for a genetic mutation. Altogether, 52% of government carriers provided no
      coverage for patients with a strong family history, and 50% provided no coverage
      in patients with a known genetic mutation; 44% of governmental carriers had no
      policy for either clinical scenario. Limited health insurance coverage for
      prophylactic thyroidectomy is offered in both private and governmental plans,
      with variations in coverage. As genetic testing becomes more widespread and with
      the potential identification of a gene predisposing to familial nonmedullary
      thyroid cancer, more uniform policies should be established to enable appropriate
      high risk candidates broader, equal coverage and access to these procedures.

PMID- 12045865
TI  - Surgical resection of unilateral lung metastases: is bilateral thoracotomy
      necessary?
AB  - Surgical resection of lung metastases is routine procedure for selected patients
      with pulmonary nodules and solid tumors. In some cases, patients present with
      unilateral pulmonary metastases amenable to surgical resection. Surgeons are
      still divided between unilateral approach directed to the radiologically detected
      nodules, or bilateral exploratory thoracotomy. This study evaluates the need for
      bilateral thoracotomy in patients diagnosed with unilateral lung metastases. A
      retrospective evaluation was made of a prospective database from a single
      institution (1990-1997) of all consecutive patients (n = 267) diagnosed on
      admission with unilateral (n = 179) or bilateral (n= 88) lung nodules.
      Ipsilateral thoracotomy was performed on all patients with unilateral disease.
      Bilateral thoracotomy was performed on all patients with bilateral lung
      metastases. HISTOLOGY: adenocarcinoma (25%), osteosarcoma (23%), squamous cell
      carcinoma (18%), soft-tissue sarcoma (18%), and other (16%). Median follow-up was
      17 months. Contralateral disease-free survival and overall survival were
      determined. Univariate and multivariate analyses were performed to determine
      prognostic factors for overall and contralateral disease-free survival. The two
      groups of patients with confirmed bilateral metastases (synchronous or
      metachronous) were compared. Actuarial overall 5-year survival was 34.9%.
      Contralateral recurrence-free 6-month, 12-month, and 5-year survival were 95%,
      89%, and 78%, respectively. Patients who experienced recurrence in the
      contralateral lung within 3, 6, or 12 months had an overall 5-year survival rate
      of 24%, 30%, and 37%, respectively. When patients with recurrence in the
      contralateral lung were compared to patients with bilateral metastases on
      admission, there was no significant difference in overall survival. Only
      histology and the number of pathologically proven metastases significantly (p <
      0.05) predicted recurrence in the contralateral lung. Bilateral exploration of
      unilateral lung metastases is not warranted in all cases. Most patients will have
      only unilateral disease, and delaying contralateral thoracotomy until disease is
      detected radiologically does not appear to affect outcome.

PMID- 12045866
TI  - Dysphagia and clinical outcome after laparoscopic Nissen or Rossetti
      fundoplication: sequential prospective study.
AB  - Laparoscopic fundoplication represents the most widely used operation in the
      surgical treatment of gastroesophageal reflux disease (GERD). Besides being
      operator-dependent, the clinical outcome (efficacy and side-effects) seems also
      to be dependent on the specific surgical technique. In this prospective trial we
      compared the results of two groups of patients who were submitted sequentially to
      the Rossetti or Nissen fundoplication procedure. Dysphagia, other side effects,
      and clinical outcome were evaluated early after surgery and at 6 and 12 months
      after the operation. Although both procedures were clinically effective, there
      was a significant trend toward less postoperative dysphagia in the Nissen group.
      In these patients the incidence of early dysphagia was significantly lower than
      that observed in those submitted to the Rossetti fundoplication. In addition,
      Nissen patients experienced a significantly smaller number of days with
      dysphagia. One year after surgery, however, the two procedures proved equally
      successful without any significant difference in dysphagia incidence. Complete
      fundic mobilization should therefore be advised to reduce the incidence of early
      troublesome dysphagia.

PMID- 12045867
TI  - Long-term surgical outcome of noninvasive and minimally invasive intraductal
      papillary mucinous adenocarcinoma of the pancreas.
AB  - The objective of this study was to clarify the long-term outcome after surgical
      resection in patients with noninvasive and minimally invasive intraductal
      papillary mucinous adenocarcinoma. We performed a retrospective review of the
      clinicopathological features and outcome in patients who underwent pancreatic
      resection for noninvasive and minimally invasive intraductal papillary mucinous
      adenocarcinoma between November 1982 and December 1997 at Chiba University
      Hospital. Minimally invasive structures were pathologically observed in five
      cases. The mean age of patients with either noninvasive (n = 16) or minimally
      invasive n = 5) adenocarcinoma was 61 years. Of the patients with minimally
      invasive adenocarcinoma, 4 had abdominal pain. Conversely, 7 patients with
      noninvasive adenocarcinoma had no complaint. The mean size of noninvasive and
      minimally invasive tumors was 2.5 cm (range 0.8 to 4.0) and 3.3 cm (range 2.5 to
      4.5), respectively. The overall 5-year and 10-year survival rates for all 21
      patients were 89% and 47%, respectively. Disease recurred in 3 patients; 2
      patients with minimally invasive adenocarcinoma and 1 with noninvasive
      adenocarcinoma. Recurrence sites were peritoneum = 2) and main pancreatic duct of
      the remnant pancreas (n = 1); 5 disease-free patients died of unrelated causes.
      The remaining 13 patients are alive and disease free 3 to 12 years after surgery.
      Noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma
      had a favorable prognosis after surgical treatment.

PMID- 12045868
TI  - Evaluation of numerical sediment quality targets for the St. Louis River Area of
      Concern.
AB  - Numerical sediment quality targets (SQTs) for the protection of sediment-dwelling
      organisms have been established for the St. Louis River Area of Concern (AOC), 1
      of 42 current AOCs in the Great Lakes basin. The two types of SQTs were
      established primarily from consensus-based sediment quality guidelines. Level I
      SQTs are intended to identify contaminant concentrations below which harmful
      effects on sediment-dwelling organisms are unlikely to be observed. Level II SQTs
      are intended to identify contaminant concentrations above which harmful effects
      on sediment-dwelling organisms are likely to be observed. The predictive ability
      of the numerical SQTs was evaluated using the matching sediment chemistry and
      toxicity data set for the St. Louis River AOC. This evaluation involved
      determination of the incidence of toxicity to amphipods ( Hyalella azteca) and
      midges (Chironomus tentans) within five ranges of Level II SQT quotients (i.e.,
      mean probable effect concentration quotients [PEC-Qs]). The incidence of toxicity
      was determined based on the results of 10-day toxicity tests with amphipods
      (endpoints: survival and growth) and 10-day toxicity tests with midges
      (endpoints: survival and growth). For both toxicity tests, the incidence of
      toxicity increased as the mean PEC-Q ranges increased. The incidence of toxicity
      observed in these tests was also compared to that for other geographic areas in
      the Great Lakes region and in North America for 10- to 14-day amphipod (H.
      azteca) and 10- to 14-day midge (C. tentans or C. riparius) toxicity tests. In
      general, the predictive ability of the mean PEC-Qs was similar across geographic
      areas. The results of these predictive ability evaluations indicate that
      collectively the mean PEC-Qs provide a reliable basis for classifying sediments
      as toxic or not toxic in the St. Louis River AOC, in the larger geographic areas
      of the Great Lakes, and elsewhere in North America.

PMID- 12045869
TI  - An evaluation of the use of colonized periphyton as an indicator of wastewater
      impact in near-coastal areas of the Gulf of Mexico.
AB  - Receiving water impacts of point source discharges to the Gulf of Mexico are
      seldom reported on indigenous flora. The objective of this research was to
      evaluate the ability of colonized periphyton to provide this information. Water
      quality and biomass and pigment concentrations of the periphyton were determined
      at 27 stations located above and below 8 wastewater discharges. Most
      physicochemical parameters and concentrations of pesticides and PCBs were either
      unchanged or below detection in the receiving waters, which contrasted occasional
      increases in concentrations of several trace metals and nutrients. The response
      of the periphyton was specific to the wastewater, colonization station, response
      parameter, and colonization period. Statistically significant differences in
      biomass and pigment content occurred for at least one colonization station
      located below each of the eight outfalls. This represented a total of 18 of the
      21 stations located in wastewater-impacted areas. Phytostimulation was more
      common than inhibition. Ash-free dry weight increased, on average, by 181% (+/- 1
      SD = 123%) and chlorophyll a increased by 356% (+/- 593%) in wastewater-impacted
      areas. The in situ phytostimulation paralleled the stimulatory trend observed in
      standardized NPDES whole effluent tests conducted with cultured microalgae for
      four of eight wastewaters. The use of colonized periphyton as an indicator of
      wastewater impact was not simple. Spatial variation in response needs
      consideration to ensure relevancy of the results if this assessment methodology
      is used for near-coastal wastewater hazard evaluations.

PMID- 12045870
TI  - Algicidal effectiveness of Clearigate, Cutrine-Plus, and copper sulfate and
      margins of safety associated with their use.
AB  - Laboratory studies of algicide toxicity to algal species provide information to
      improve the efficacy and efficiency of copper-containing algicides in actual
      field situations. The objectives of this study were (1) to measure the influence
      of copper form, initial concentration, and duration of exposure on the response
      of Raphidocelis subcapitata, a planktonic freshwater green alga; (2) to determine
      the contact time required for these copper-containing algicides (Clearigate,
      Cutrine-Plus, and copper sulfate) and the target species to obtain control; (3)
      to measure the critical burden of the three algicides required to obtain control
      of R. subcapitata; (4) to measure the residence time of the copper applied as the
      algicides in the water column of three waters having different water
      characteristics ( i.e., alkalinity, hardness, pH, and conductivity); and (5) to
      contrast exposures of copper (as algicides) required to control algae and the
      lower thresholds causing adverse effects on sensitive nontarget animal species.
      Algal control (EC(100)) was accomplished at 55.8, 117.5, and 187.5 microg Cu/L
      for CuSO(4), Cutrine-Plus and Clearigate with a contact time of 3 days in all
      cases. The critical burdens of copper (concentration sorbed by the algae) were
      4.2, 7.3, and 7.9 microg Cu/mg algae (dry weight) for CuSO(4), Cutrine-Plus, and
      Clearigate, respectively. Because algicide toxicity generally decreases as cell
      density increases, the density of cells in algal blooms may hamper algicide
      effectiveness even at maximum label application rates. Determinations of critical
      burdens for algicides and target algal species provide necessary information to
      forecast the performance of algicide applications in field situations. The margin
      of safety ( i.e., the difference between the concentration where control of algae
      was obtained and the lower threshold concentration causing adverse effects on
      nontarget species) was greatest for Cutrine-Plus. However, the margins of safety
      are minimal (< 0, 12.5, and 82.5 microg Cu/L for Ceriodaphnia dubia exposed to
      CuSO(4), Clearigate, and Cutrine-Plus, respectively) when they are applied
      according to their labels.

PMID- 12045871
TI  - Toxicity of cadmium and zinc mixtures to Diplostomum spathaceum (Trematoda:
      Diplostomidae) cercarial survival.
AB  - The toxicity of cadmium and zinc mixtures at concentrations ranging from 0.1 to
      10,000 microg/L was investigated against the survival of the free-living
      cercarial stage of the parasitic fluke Diplostomum spathaceum. Cercariae were
      exposed to metal mixtures of equal concentration, metal mixtures of unequal
      concentration, and low-dose pretreatment followed by high-dose exposure mixtures.
      Under all exposures cercarial survival was increased compared to that achieved
      with single metals. At exposures with metal mixture of equal concentration in the
      range 0.1-100 microg/L survival was increased compared to that achieved by
      controls. The mechanism of metal toxicity and their effects on cercarial survival
      are discussed.

PMID- 12045872
TI  - Indirect effects of heavy metals on parasites may cause shifts in snail species
      compositions.
AB  - We studied the direct and indirect effects of pollution on the distributions and
      abundances of two closely related species of pulmonate freshwater snails.
      Physella columbiana is more numerous at heavy metal-polluted lakes, and Lymnaea
      palustris is more numerous at reference lakes. Both species are present at all
      sites, as are predatory bluegill sunfish (Lepomis macrochirus). The direct
      effects examined included the snails' growth and reproduction in both the
      presence and absence of heavy metals and their short-term survival when exposed
      to large concentrations of heavy metals. The indirect effects were the species'
      ability to elude capture by sunfish and the diversity and abundance of parasites
      within the snails. We found that heavy metals had little direct effect on growth
      and reproduction and that both species acquired similar levels of metals in their
      tissues. Interestingly, P. columbiana (the more abundant species in polluted
      lakes) actually exhibited higher recruitment in the absence of metals than did L.
      palustris (reference lakes). L. palustris has life history characteristics that
      favor increased growth and reduced reproduction. These characteristics resulted
      in decreased predation of adults by gape-limited predators and a greater ability
      to cope with heavy parasite burdens. P. columbiana exhibited slower growth, which
      resulted in increased predation although higher reproduction rates may
      compensate.The major effect of heavy metals on species distributions was indirect
      on the snails' parasites. Parasites appeared to be very susceptible to metals,
      and this resulted in lower parasite diversity and intensities at polluted sites
      for both species of snails. P. columbiana may only be able to outcompete L.
      palustris at polluted sites due to the indirect effects of heavy metals; the
      negative effect of heavy metals on parasites, and a proposed negative effect of
      metals on the foraging ability of sunfish that favors the faster-reproducing P.
      columbiana.

PMID- 12045873
TI  - Teratogenic effects of amitraz, 2,4-dimethylaniline, and paraquat on developing
      frog (Xenopus) embryos.
AB  - Developmental effects of amitraz (acaricide), its metabolite (2,4
      dimethylaniline), and paraquat (herbicide) on embryos of a nontarget organism,
      Xenopus laevis, were investigated. Following the standard protocol of the
      American Society for Testing and Materials (ASTM), the experiments were carried
      out using native Xenopus frogs. There was a drastic increase in mortality from 24
      h to 96 h for paraquat, but 2,4-dimethylaniline showed no mortality at the
      highest concentration tested (100 mg/L). The 96-h LC(50) values were 0.67, 3.27,
      and >>100 mg/L for paraquat, amitraz, and 2,4-dimethylaniline, respectively. At
      concentrations higher than 0.2 mg/L of paraquat all the embryos were malformed,
      whereas growth reduction was apparent at all test concentrations (0.1-5 mg/L).
      The most common teratogenic effects were flexures of the notochord and stunting
      of growth. Edema was the most common effect of amitraz on the embryos, and 100%
      of the surviving embryos in 5 mg/L were edematous. The 96-h EC(50) (malformation)
      values were 1.21 (95% CI 0.48-3.03) and 0.18 (95% CI 0.16-0.20) mg/L for amitraz
      and paraquat, respectively. The ratio of 96-h LC(50) to 96-h EC(50)
      (malformation), i.e., the teratogenicity index (TI) were 2.7 and 3.72 for amitraz
      and paraquat, respectively, and for 2,4-dimethylaniline (TI > 5) all the embryos
      in 25 mg/L showed observable pigment loss and encephalomegaly. This shows that
      paraquat and the degradation product of amitraz, 2,4-dimethylaniline, should be
      classified as teratogens. Teratogenic risks of massive application of these
      pesticides on Kenyan farms should therefore be considered.

PMID- 12045874
TI  - Bisphenol A accumulation in the freshwater clam Pisidium amnicum at low
      temperatures.
AB  - Toxicokinetics of (14)C-labeled bisphenol A (BPA) was studied in the small
      freshwater clam Pisidium amnicum at four ecologically relevant low temperatures
      (2, 6, 8, and 12 degrees C). The uptake clearance (k(u)) of BPA increased from
      1.49 to 6.55 ml x g(-1) x h(-1) as temperature increased from 2 to 8 degrees C
      but decreased slightly again at the highest temperature. The depuration of BPA
      was very slow and statistically insignificant at 2 degrees C, but the depuration
      rate ( k(d)) increased linearly as temperature increased from 2 to 12 degrees C.
      The longest half-life of BPA in clam tissues, 221 h, was found at the lowest
      temperature, and the highest bioconcentration factor of 144 was measured at 8
      degrees C. Data show that P. amnicum accumulates BPA so that the bioconcentration
      factor rises over 100 at each temperature tested. Further, the data demonstrate
      the importance of temperature on the processes that control both the uptake and
      elimination of this compound.

PMID- 12045875
TI  - Toxicity of 17alpha-ethinylestradiol and bisphenol A to the freshwater Cnidarian
      Hydra vulgaris.
AB  - Estrogens and estrogen mimics that enter the environment are known to present a
      serious threat to the development and reproduction of vertebrates by disrupting
      their normal endocrine function. There is also concern that such chemicals may be
      damaging to invertebrates. In this study, Hydra vulgaris, a member of the
      Cnidaria, an evolutionarily primitive group of invertebrates present before the
      divergence of the protostomes and deuterostomes, was exposed to the synthetic
      estrogen 17alpha-ethinylestradiol (EE2) and bisphenol A (BPA), both of which are
      known to be estrogenic in fish. Effects on polyp survival, structure, and
      regeneration (and sexual reproduction for EE2) were examined and mortality was
      recorded at high concentrations, with 96-h LC(50)s of 3.8 mg/L and 6.9 mg/L for
      EE2 and BPA, respectively. The structure and physiology of polyps was adversely
      affected at concentrations greater than 58 microg/L EE2 and 42 microg/L BPA.
      There was a concentration-related inhibition of regeneration above 150 microg/L
      EE2 and 460 microg/L BPA. Sexual reproduction was only impaired at 500 microg/L
      EE2. These results clearly suggest that the signaling processes necessary for the
      control and regulation of cell movement and differentiation during normal
      development, regeneration, and sexual reproduction in H. vulgaris are not
      disrupted by estrogenic pollutants at low environmentally relevant
      concentrations.

PMID- 12045876
TI  - Accumulations of nitrite and nitrate in the tissues of Penaeus monodon exposed to
      a combined environment of elevated nitrite and nitrate.
AB  - Penaeus monodon (11.86 +/- 0.63 g) exposed individually to six different nitrite
      and nitrate regimes [nitrite at 0.002 (control), 0.360, and 1.455 mM combined
      with nitrate at 0.005 (control) and 7.275 mM] in 25 ppt sea water were examined
      for the nitrite and nitrate concentrations in tissues and nitrite uptake and
      nitrate uptake after 24 h in 25.3 degrees C. In P. monodon following exposure to
      1.455 mM nitrite only, nitrite levels increased by factors of 0.33, 1.05, 1.36,
      1.79, 2.10, 2.16, 2.21, and 3.58 in muscle, hepatopancreas, gill, foregut,
      hemolymph, heart, eyestalk, and midgut, respectively, over the ambient nitrite
      level. In P. monodon, following exposure to combined solutions of 1.455 mM
      nitrite and 7.275 mM nitrate, nitrite levels were factors of 0.34, 1.05, 1.44,
      1.86, 2.21, 2.30, 2.67, and 3.83 in muscle, hepatopancreas, gill, foregut, heart,
      hemolymph, eyestalk, and midgut, respectively, over the ambient nitrite levels,
      whereas nitrate levels were factors of 0.06, 0.11, 0.27, 0.29, 0.45, 0.51, 0.57,
      and 0.61 in muscle, hepatopancreas, foregut, heart, hemolymph, gill, midgut, and
      eyestalk, respectively, over the ambient nitrate levels. It is concluded that
      incorporation of nitrite is converted to nitrate in midgut, heart, hemolymph,
      foregut, and eyestalk, whereas incorporation of nitrate in tissues is converted
      to nitrite and accumulated in eyestalk when P. monodon are exposed to combined
      nitrite and nitrate environments.

PMID- 12045877
TI  - Environmental, biological, and methodological factors affecting cholinesterase
      activity in walleye (Stizostedion vitreum).
AB  - Organophosphorus (OP) insecticides have high acute toxicity toward many nontarget
      vertebrate and invertebrate organisms, but direct measurement of OPs in
      environmental samples is difficult because their concentrations may fall below
      detection limits within hours to days after entering aquatic ecosystems. Because
      OPs exert toxicity through cholinesterase (ChE) inhibition, which may persist for
      up to several weeks, ChE inhibition has been widely used in aquatic ecosystems as
      a biomarker for OP exposure in aquatic organisms. However, the biological,
      environmental, and methodological factors affecting ChE activity have not been
      well documented and must be considered and understood before ChE activity can be
      used as a dependable indicator of OP exposure to aquatic organisms. This study
      examined the influence of water temperature, size of larval and juvenile walleye
      (Stizostedion vitreum), stress, long-term storage, postmortem changes, and
      methods of euthanasia on ChE activity. Water temperature (17.2, 20.9, and 24.6
      degrees C), stress, long-term storage (up to 180 days), postmortem changes, and
      method of euthanasia had no effect on ChE activity of walleye. There was a strong
      positive correlation (r = 0.87) between whole body ChE activity and total length
      (7.2-17.9 mm) for larval walleye, but a negative correlation between brain ChE
      activity and total length (59-164 mm) for juvenile walleye (r = 0.75). Because
      size, age, and development may affect ChE activity, fish of similar size should
      be used when evaluating the effects of ChE inhibitors. If fish of similar size
      are not available, it is recommended that relations between size, age, and
      development be understood so estimates of variation in ChE activity can be made.

PMID- 12045878
TI  - Organochlorine chemical residues in fish from the Mississippi River basin, 1995.
AB  - Fish were collected in late 1995 from 34 National Contaminant Biomonitoring
      Program (NCBP) stations and 13 National Water Quality Assessment Program (NAWQA)
      stations in the Mississippi River basin (MRB) and in late 1996 from a reference
      site in West Virginia. Four composite samples, each comprising (nominally) 10
      adult common carp (Cyprinus carpio) or black bass (Micropterus spp.) of the same
      sex, were collected from each site and analyzed for organochlorine chemical
      residues by gas chromatography with electron capture detection. At the NCBP
      stations, which are located on relatively large rivers, concentrations of
      organochlorine chemical residues were generally lower than when last sampled in
      the mid-1980s. Residues derived from DDT (primarily p,p'-DDE) were detected at
      all sites (including the reference site); however, only traces (<or= 0.02
      microg/g) of the parent insecticide (p,p'-DDT) were present, which indicates
      continued weathering of residual DDT from past use. Nevertheless, concentrations
      of DDT (as p,p'-DDE) in fish from the cotton-farming regions of the lower MRB
      were great enough to constitute a hazard to fish-eating wildlife and were
      especially high at the NAWQA sites on the lower-order rivers and streams of the
      Mississippi embayment. Mirex was detected at only two sites, both in Louisiana,
      and toxaphene was found exclusively in the lower MRB. Most cyclodiene pesticides
      (dieldrin, chlordane, and heptachlor epoxide) were more widespread in their
      distributions, but concentrations were lower than in the 1980s except at a site
      on the Mississippi River near Memphis, TN. Concentrations were also somewhat
      elevated at sites in the Corn Belt. Endrin was detected exclusively at the
      Memphis site. PCB concentrations generally declined, and residues were detected
      (>or= 0.05 microg/g) at only 35% of the stations, mostly in the more
      industrialized parts of the MRB.

PMID- 12045879
TI  - Rainbow trout gills are a sensitive biomarker of short-term exposure to
      waterborne copper.
AB  - Hepatic copper levels may not indicate short-term exposure to waterborne copper
      in teleosts. Significantly higher copper loads were found in the gills of rainbow
      trout exposed to 105 microg x L(-1) total measured copper for a period of 24 h
      than in control animals where no differences were recorded in hepatic copper
      levels. A second experiment exposing trout to 153 microg x L(-1) total measured
      copper also demonstrated significant differences in branchial copper levels
      between control and exposed animals after 3 h exposure. The ratio of the copper
      load in the gills to the liver, and copper/zinc ratios of the gills were also
      examined. After exposure to 105 microg x L(-1) for 24 h both gill/liver copper
      ratios and Cu/Zn ratios in exposed animals were significantly greater than in
      control animals. After 12 h exposure to 153 microg x L(-1) total measured copper
      the gill Cu/Zn ratio was significantly greater than in control animals. These
      data indicate the gills may be a better indicator of short-term exposure than the
      liver.

PMID- 12045880
TI  - Cattle as biomonitors of soil arsenic, copper, and zinc concentrations in Galicia
      (NW Spain).
AB  - Determination of soil concentrations of trace and pollutant metals over large
      spatial areas requires laborious and expensive sampling effort. In this study, we
      examined the feasibility of using calves as biomonitors of soil semimetal and
      trace metal concentrations in Galicia (NW Spain), a region in which calves are
      predominantly reared on grass or locally grown forage. We determined the
      concentrations of arsenic, copper, and zinc in the liver, kidney, muscle, and
      blood of calves from across Galicia and related them to the metal concentrations
      in the soil from the areas in which the animals were reared. For each element,
      liver (but not usually kidney, muscle, or blood) concentrations were
      significantly elevated in animals from areas with higher soil concentrations.
      Liver arsenic concentrations were only markedly greater in animals from areas
      with soil arsenic levels > 20 mg/kg, and calves may not be sensitive enough
      biomonitors of background variation in soil levels, although they may be useful
      for monitoring anthropogenic arsenic contamination. Copper and zinc liver levels
      increased progressively with soil levels, and the pattern was especially marked
      for copper. The relatively unusual copper metabolism of cattle and other
      ruminants may make them particularly good biomonitors for environmental
      concentrations of this metal.

PMID- 12045881
TI  - Accumulation of heavy metals in Caspian seals (Phoca caspica).
AB  - Concentrations of heavy metals (Fe, Mn, Zn, Cu, Pb, Ni, Cd, Co, and Hg) were
      determined in the muscle, liver, and kidney of 42 Caspian seals and fishes
      collected from the Caspian Sea in 1993. Higher Mn and lower Fe and Cu
      concentrations were found in the liver in comparison with other marine pinnipeds.
      Lower Cu concentrations in the liver appear to be a common feature in small seals
      belonging to subgenus Pusa, which include ringed, Baikal, and Caspian seals.
      However, low Fe and high Mn in livers were specific to Caspian seal.
      Concentrations of toxic metals such as Hg and Cd were relatively low. Pinniped
      species can be divided into two groups, based on accumulations of Cd or Hg in the
      liver. Interestingly, it was found that Cd-accumulating groups feed on
      invertebrates, whereas the preferred diet of Hg accumulators is fish. Caspian
      seals seemed to belong to the Hg-accumulating group.Cd and Hg concentrations in
      the liver and kidney of young animals increased with age. Mercury concentrations
      in adult animals increased with age continuously, whereas Cd concentrations in
      adult animals decreased. This trend might be due to preferential feeding habits
      and shift in ratio of Hg and Cd in the diet ( i.e., invertebrates to fish).

PMID- 12045882
TI  - Levels of environmental contaminants in human follicular fluid, serum, and
      seminal plasma of couples undergoing in vitro fertilization.
AB  - Environmental chemicals are thought to adversely affect human reproductive
      function, however there are no studies that have explored the association between
      failed fertilization and exposure of both partners to environmental contaminants.
      Therefore, we collected blood and follicular fluid from the female partner and
      seminal plasma from the male partner of 21 couples attending an in vitro
      fertilization (IVF) program, in order to determine the extent of the existence of
      environmental chemicals in these fluids. Any relationship to the outcome of IVF
      was also considered. Sera and fluids were analysed for a variety of contaminants,
      including polychlorinated biphenyls, pesticides, cotinine, and the steroids
      progesterone and estradiol. Of the couples examined, 18 had fertilizations, three
      of whom became pregnant. There were no fertilizations in three other couples. The
      contaminants most frequently found in follicular fluid, more than 50% of the
      samples tested, were p,p'-DDE, mirex, hexachloroethane, 1,2,4-trichlorobenzene,
      PCB 49, PCB 153, and PCB 180. Cadmium was detected in eight of 21 (38.1%) samples
      of follicular fluid whereas cotinine was detected in 18 (85.7%). Residue levels
      of p,p'-DDE, endosulfan I, PCB 99, PCB 138, PCB 153, PCB 180 were quantified in
      more than 50% of the sera samples examined. Seminal plasma was relatively free of
      pollutants with mirex being the most frequently detected contaminant found in
      seven of 21 (33.3%) samples. Mirex could not be detected in the seminal plasma of
      the husbands whose partner's oocytes failed to fertilize whereas significant
      levels of mirex were found in the seminal plasma of all couples who had a
      pregnancy. Cadmium was also found in the follicular fluid of these pregnant
      subjects. No relationship was found between follicular fluid cotinine in pregnant
      and non-pregnant subjects. Where identical contaminants were found in both sera
      and follicular fluids, the levels were about twofold higher in serum and were
      positively correlated in both fluids. Fertilization was negatively correlated
      with serum and follicular fluid p,p'-DDE whereas pregnancy was positively
      correlated with follicular fluid PCB 49. These data reveal that more than 50% of
      the population of women attending a fertility program have had exposure to
      environmental chemicals sufficient to produce detectable concentrations in their
      serum and ovarian follicular fluid. Of the chemical contaminants detected in the
      serum and follicular fluid of these women, p,p'-DDE was the most frequently
      detected, had the highest residue levels, and was associated with failed
      fertilization.

PMID- 12045883
TI  - Risk factors for diabetic retinopathy in the Cree of James Bay.
AB  - BACKGROUND: The purpose of this project was to evaluate risk factors for diabetic
      retinopathy in the Cree population of James Bay, Ontario. METHODS: A
      retrospective cohort design was employed. The cohort was made up of all known
      individuals who had previously been diagnosed with diabetes in the communities of
      Moose Factory and Moosonee, Ontario. Hypertension, body-mass index, serum lipid
      levels, renal function status, and hemoglobin A1C were the main exposures of
      interest. Values for these variables were determined from a retrospective chart
      review and were sought for each individual for a five-year interval beginning one
      year following the diagnosis of diabetes. Relative risks for the association of
      these variables with diabetic retinopathy were determined through both univariate
      and multivariate Poisson regression. The main outcome of interest in this study
      was the presence or absence of any diabetic retinopathy in either eye, as
      determined by a retinal specialist. RESULTS: Significant univariate risks for the
      development of retinopathy included duration of diabetes, body-mass index,
      hemoglobin A1C, fasting blood glucose, insulin treatment, and serum cholesterol
      levels. In multivariate analyses, predictors of diabetic retinopathy included
      body-mass index, insulin treatment, and serum cholesterol levels. An increase in
      body-mass index reduced the risk of diabetic retinopathy (Relative Risk [RR] 0.64
      per five kg/m( 2), 95% Confidence Interval [CI] 0.04 to 1.00). Insulin therapy
      was associated with an increased risk of retinopathy when compared to individuals
      on dietary therapy alone (Relative Risk [RR] 4.71, 95% Confidence Interval [CI]
      1.16 to 19.16). For individuals with serum cholesterol levels above the average
      for the cohort, 5.2 mmol/L, the risk of retinopathy was increased (Relative Risk
      [RR] 2.38, 95% Confidence Interval [CI] 0.98 to 5.79). INTERPRETATION: Elevated
      serum cholesterol, lower body-mass index and insulin treatment were all
      associated with an increased risk of diabetic retinopathy in the Cree of James
      Bay, Ontario.

PMID- 12045884
TI  - Digital photographic screening for diabetic retinopathy in the James Bay Cree.
AB  - This study evaluates a single, 45-degree fundus image from a non-mydriatic camera
      for the triage of subjects at risk for diabetic retinopathy. A complete retinal
      assessment by a retina specialist was the main comparator for the camera. Inter
      observer agreements were calculated for the reading of digital images with
      different grades of retinopathy. Two hundred eyes of 100 consecutive subjects
      were evaluated as part of the James Bay diabetic retinopathy screening project;
      62% of subjects had no retinopathy, 12% had microaneurysms only, 24% had non
      proliferative retinopathy, 5% had clinically significant macular edema (CSME),
      and 2% had proliferative disease (PDR). The Kappa statistic for two independent
      observers was 0.85 (p < 0.001) for the identification of retinopathy from the
      digital images. The sensitivity of the digital camera for the evaluation of any
      retinopathy was 84.4%, for CSME and/or PDR it was over 90%. The use of a single
      digital retinal image for the evaluation of diabetic retinopathy was performed
      with a high degree of inter-observer concordance and a high degree of
      sensitivity.

PMID- 12045885
TI  - Postmenopausal hormone use and lens opacities.
AB  - PURPOSE: Women are at higher risk for age-related cataract than men, and it has
      been hypothesized that this difference is due in part to gender-related hormonal
      differences. METHODS: We investigated the association between postmenopausal
      hormone use and lens opacities in a population of 480 postmenopausal women from
      the Nurses' Health Study for whom we had prospectively collected exposure data.
      Participants received standardized eye exams; the Lens Opacity Classification
      System III (LOCS III) was used to measure the degree of opacification. RESULTS: A
      total of 342 women had some opacity in one or both eyes. Overall, we did not
      observe a significant association between current hormone use and presence of any
      type of opacity (compared to never users, multivariate relative risk: 0.85; 95%
      confidence interval (CI): 0.54-1.34). In ordinal logistic regression compared to
      never users, current hormone users had multivariate relative risks of cortical
      opacities of 0.80 (95% CI: 0.54-1.19) and for past users the relative risk was
      0.76 (95% CI: 0.48-1.22). For nuclear opacities, the comparable relative risk for
      current use of hormones was 0.77 (95% CI: 0.52-1.13), and for past use the
      relative risk was 1.48 (95% CI: 0.92-2.34). Current use of estrogen-only
      preparations was associated with a 49% decreased risk of nuclear opacities
      compared to never use (multivariate relative risk 0.51, 95% CI: 0.29-0.89).
      CONCLUSIONS: While the overall findings are null, they do not exclude the
      possibility of a protective effect, particularly among current estrogen users.

PMID- 12045886
TI  - Levels of agreement between parents' and children's reports of near work.
AB  - PURPOSE: To assess whether parents and children report the same information
      regarding children's near vision activities when given similar questionnaires.
      METHODS: Data from questionnaires administered to 406 children and their parents
      were analyzed to evaluate the agreement between parent and child reports. The
      questionnaires were completed during the 1994 testing of the Orinda Longitudinal
      Study of Myopia. Each child and parent was asked to categorize how often the
      child reads for pleasure. In addition, each subject was asked to estimate how
      many hours per week were spent in each of five visual activities. The weighted
      kappa statistic, paired t-tests, and polytomous logistic regression were used for
      analyses. RESULTS: A weighted kappa = 0.42 (moderate agreement) was found in the
      comparison of child-reported vs. parent-reported classification of reading.
      Agreement between parent- and child-reported number of hours spent doing homework
      (0.21), reading for pleasure (0.31), watching television (0.31), playing video
      games (0.31), and engaging in sports/outdoor activities (0.26) was fair for each
      activity. CONCLUSIONS: Although the results indicate fair to moderate levels of
      agreement, better methods of reporting near-work activities are needed for future
      myopia research.

PMID- 12045887
TI  - Prevalence of diabetic retinopathy and eye care in a rural area of Spain.
AB  - OBJECTIVE: To study the prevalence of diabetic retinopathy (DR) in a sample of
      3544 patients living in a rural area of the province of Valladolid, Spain; as
      well as to estimate the current eye care to the diabetic population. METHODS:
      Participants received a comprehensive ocular examination in their local area
      where they resided and a grading of DR was made using standard protocols.
      Physicians then provided us with the systemic and demographic data. RESULTS: The
      population studied included 175 younger-onset and 3344 older-onset patients, all
      of whom were under physicians' care, distributed in an 18-county-area far from
      the urban center. Mean duration of the disease was 7.89 +/- 7.7 years (range 0 to
      59 years). 73% of participants had not received ophthalmologic care the preceding
      year and 63.6% had not received a dilated eye examination either. The prevalence
      of DR was 20.9%; macular edema was found in 5.7% of the patients. Differences in
      participation were found among counties and these also correlated with
      differences in prevalence of DR. Prevalence of DR in the younger-onset group was
      25.6% and 14.81% in insulin- and non-insulin-dependent patients, respectively. In
      the older-onset group, it was present in 48.6% and 14.7% of insulin- and non
      insulin-dependent patients. Patients with retinopathy were older, with a longer
      duration of disease, were insulin dependent and had had less eye care.
      CONCLUSIONS: Deficient screening of ophthalmic disease in diabetic patients
      should be improved, especially in isolated areas, in order to reduce DR in this
      group. Insulin-dependent older-onset patients with a longer duration of diabetes
      had a higher frequency of these complications.

PMID- 12045888
TI  - Comparison of Goldmann applanation tonometry with the Tonopen for measuring
      intraocular pressure in a population-based glaucoma survey in rural West Bengal.
AB  - AIM: This study was undertaken to compare the measurement of intraocular pressure
      (IOP) in a population-based glaucoma survey by the Goldmann Applanation Tonometer
      (GAT) and the Tonopen with respect to IOP readings, the time required to measure
      IOP and subjects' preference for the two instruments. The purpose of the study
      was to see which of the two instruments could be more suitable in a rural survey,
      particularly house-to-house, in trying to find cases of advanced glaucoma.
      METHOD: The study was conducted on a total of 203 subjects as a part of a
      population-based glaucoma survey. The IOP of one randomly selected eye of each
      subject was measured, first with the GAT and subsequently with the Tonopen. The
      time taken for each procedure was noted and subjects' preference was ascertained.
      RESULTS: The mean of the paired differences between the readings of the two
      instruments (Tonopen minus GAT) was 1 mm Hg with a standard deviation of 2.28.
      The Tonopen readings were within +/-3 mm Hg of the GAT readings in 86.2% of eyes.
      In 7.4% of the eyes the paired differences were > or =+/-5 mm Hg. Measurement of
      IOP by the Tonopen was much quicker, the mean time difference being 38.7 sec.
      Subjects' preference for the Tonopen was higher. CONCLUSION: The overall
      agreement between the measurements of the two instruments was good but a small
      percentage of large difference (> or = +/-5 mm Hg in 7.4%) may be of concern in a
      population-based survey. The time to measure IOP and the subjects' preference
      were strongly in favour of the Tonopen.

PMID- 12045889
TI  - Control of SV-40 transformed RCE cell proliferation by growth-factor-induced cell
      cycle progression.
AB  - PURPOSE: To determine in SV40-immortalized rabbit corneal epithelial cells (RCE),
      whether there is conservation of parent tissue serum growth-factor-stimulated
      cytokine receptor activation and downstream intracellular signaling events
      mediating control of cell cycle progression and differentiation. METHODS:
      Immunostaining and Western blot analysis were used to measure cytokeratin K3 and
      K12 expression with AE5 and AK12 antibodies. Karyotype analysis was performed
      based on comparison of the RCE chromosomal complement with its parent tissue. EGF
      receptor activation was evaluated based on immunochemistry and Western blot
      analyses of EGF receptor dimerization and phosphorylation. Functional status of
      EGF receptor was determined through measurements of EGF-induced stimulation of
      ERK-2 activity, which is a component of the mitogen-activated protein kinase
      cascade (MAPK). This was done by immunocomplex and kinase assay using anti-ERK
      antibodies and a specific substrate. EGF-induced increases in proliferation and
      cell cycle progression were determined based on measurements of [(3)H]-thymidine
      incorporation, G(2)-specific cyclin B1 expression and cell cycle mapping.
      RESULTS: From days 7 to 14, K12 expression increased based on marked rises in the
      levels of a 55 kD band. At day 14, a 64 kD band also appeared indicative of K3
      expression. Karyotype analysis showed that there were no chromosomal losses due
      to SV-40 transformation. Upon exposure to EGF (5 ng/ml) for 1 min, EGF receptors
      were activated and formed clusters indicating that autophosphorylation and
      multimerization of the EGF receptor were occurred. In the presence of serum
      growth factors or EGF, ERK-2 kinase activity was markedly increased with a bell
      shaped time-dependent activation pattern. Cell cycle progression was analyzed in
      G(1)/S boundary synchronized RCE cells. After releasing the cells into modified
      Supplemented Hormonal Epithelium Medium containing 10% serum and DMEM/F-12
      medium, 80% of the cells had entered the S phase within 2 h. In addition, time
      dependent changes in [(3)H]-hymidine incorporation over 8 h confirmed RCE passage
      through the G(1)/S checkpoint. There were more RCE cells entered the G(2)/M phase
      of cell cycle in the 6-8 h interval after their release. Another indication of
      cell cycle progression into the G(2)/M phase was that at 8-10 h cyclin B(1)
      expression reached its maximal level. CONCLUSIONS: RCE in passage number 12-20
      are a physiologically relevant model for studies on growth factor receptor
      mediated control of cell cycle progression and differentiation in its parent
      tissue as each of these phenomena were conserved: 1) EGF-induced EGF receptor
      activation; 2) EGF-activated ERK signaling; 3) expression of cornea-specific
      differentiation markers; 4) karyotype profile; and 5) cell cycle control and
      progression.

PMID- 12045890
TI  - The role of IL-1beta in the regulation of IL-8 and IL-6 in human corneal
      epithelial cells during Pseudomonas aeruginosa colonization.
AB  - PURPOSE: Recent studies have shown that the levels of interleukin (IL)-1beta, IL
      6 and IL-8 are associated with the severity of infectious diseases. The purpose
      of this study was to investigate whether IL-1beta regulates the expression of IL
      6 and IL-8 in human corneal epithelial cells during Pseudomonas aeruginosa
      colonization. METHODS: Confluent immortalized human corneal epithelial cells were
      challenged with P. aeruginosa 6294 in the presence of anti-human IL-1beta
      antibody or matched control antibody. The cells were also challenged with
      recombinant IL-1beta protein without bacterial colonization. Expression of IL
      1beta, IL-6 and IL-8 mRNA and protein was detected by reverse transcription (RT)
      PCR and by enzyme-linked immunosorbent assay (ELISA), respectively. IL-1beta
      localization was determined by immunohistochemistry. RESULTS: Human corneal
      epithelial cells expressed low levels of IL-1beta and high levels of IL-6 and IL
      8 during P. aeruginosa colonization. Addition of IL-1beta Ab resulted in a
      significant decrease (P < 0.05) in IL-8 protein expression at 4 h, 8 h and 12 h.
      Addition of IL-1beta Ab reduced IL-6 protein expression at 8 h and increased IL-6
      protein expression at 12 h. Addition of recombinant IL-1beta protein alone
      strongly stimulated the expression of IL-8 and IL-6. Immunohistochemical staining
      showed that IL-1beta protein was present both intracellularly and extracellularly
      in P. aeruginosa colonized cells. CONCLUSIONS: IL-1beta is able to modulate
      expression of both IL-6 and IL-8 at transcriptional and post-transcriptional
      levels in human corneal epithelial cells.

PMID- 12045891
TI  - Effects of pseudophakic lens capsule opacification on optical coherence
      tomography of the macula.
AB  - PURPOSE: To report observations on the influence of posterior lens capsule
      opacification on optical coherence tomographic imaging quality and measurements
      of macular thickness. METHODS: The retrospective study included 13 eyes in 12
      patients of which 2 eyes had a healthy macula and 11 eyes had maculopathy. In all
      eyes posterior lens capsule fibrosis was present. A clinical examination
      including biomicroscopy of the macula and an in-vivo macular optical coherence
      tomography (OCT) before and after YAG-laser membranotomy had been performed.
      RESULTS: Foveal retinal thickness before and after membranotomy were highly
      correlated (R = 0.98), and no systematic difference was found between values
      obtained before vs. after membranotomy (mean thickness 318.7 +/- 92.7 microm vs.
      322.2 +/- 97.4 microm; p = 0.221). The signal-to-noise ratio increased in 11 out
      of 13 eyes after membranotomy (mean signal-to-noise ratio before 47.1 +/- 6.6 dB
      vs. 52.6 +/- 4.0 dB after; p = 0.004, the change ranging from -1.5 dB to 17 dB).
      CONCLUSIONS: The qualitative effect of the posterior lens capsule opacification
      on the OCT-scan consists primarily of a loss of signal and consequently of
      intraretinal detail, whereas total foveal retinal thickness seems to be reliably
      assessed even when posterior lens capsule opacification interfering with the
      biomicroscopic evaluation of retinal edema are present. YAG-laser membranotomy
      results in a measurable improvement in the OCT signal-to-noise ratio, but OCT
      seems to yield reliable measurements of foveal retinal thickness before
      treatment. Consequently the OCT seems to reliably diagnose a macular thickening
      although not the type of this until after removal of the posterior lens capsule
      opacification.

PMID- 12045892
TI  - The spatial distribution of macular pigment in humans.
AB  - PURPOSE: To estimate the distributions in width as well as in density of macular
      pigment (MP) in humans at different ages, imaging fundus reflectometry was
      employed as a tool to reach our aim. METHODS: Imaging fundus reflectometry was
      used to measure the macular pigment distribution in human eyes with a modified
      fundus camera to which a cooled CCD camera was attached. The fundus images were
      taken at 460 nm and 560 nm after the retina was light-adapted to completely
      bleach rhodopsin. The density of macular pigment was estimated using a model
      described in the text. The variation in density with retinal eccentricity was fit
      to Gaussian distribution. The width of MP in retinal eccentricity was estimated
      by 95% covering area of the distribution profile. A total of 54 normal people
      served as subjects. They were divided into three groups with ages of 24.8 +/- 2.6
      years (N = 24), 40.2 +/- 8.3 years (N = 13) and 67.5 +/- 7.1 years (N = 17)
      respectively. Statistical t-tests were employed to evaluate the differences in MP
      density, the half width of MP distributed (HWMPD) in retina with respect to age
      between the groups. Linear regression was also applied to reveal the
      relationships of HWMPD distribution with respect to age. RESULTS: The results
      indicate that the average MP densities are 0.23 +/- 0.08, 0.22 +/- 0.06 and 0.23
      +/- 0.06 density unit (DU) for the young to old age groups. The average MP
      density is 0.23 +/- 0.07. No statistical significant difference is found in the
      peak MP density between the groups (all p > 0.05). This result pretty agrees with
      the data that obtained from others by using optical methods. For the young to old
      age groups, the average estimated HWMPD are 2.6 degrees +/- 0.5 degrees, 3.1
      degrees +/- 0.5 degrees and 4.1 degrees +/- 0.6 degrees respectively. The
      differences between loci of HWMPD in the three groups are statistically
      significant with p = 0.0059, p < 0.0001 and p = 0.0001 for young vs. mid-age,
      young vs. old and mid-age vs. old respectively. Linear regressions for the HWMPD
      vs. age (r = 0.734, p < 0.001) implies that the macular pigment can gradually
      accumulate and spread out to the periphery of retina through our life span with
      an increase rate of approximately 0.03 degrees /year. CONCLUSIONS: The
      accumulation of MP is reflected by the broader area in the macula lutea due to
      age, but no significant change is observed in peak density. The cause of the
      extension in the macular area with respect to age is unknown.

PMID- 12045893
TI  - Increased severity of herpes simplex virus type 1-induced keratitis in Hox A5
      transgenic mice.
AB  - PURPOSE: Herpes simplex virus type 1 is a major cause of stromal keratitis and
      blindness in humans. Understanding of the role of host genes in the pathogenesis
      of herpes stromal keratitis is limited. We used a transgenic mouse model to
      examine the effect of a host gene, Hox A5 (which binds to the TAATGARAT sequence
      in the promoter regions of HSV-1 immediate early genes and increases HSV-1
      replication), on the pathogenesis of HSV-1 induced stromal keratitis. METHODS:
      Corneas of wildtype and Hox A5 transgenic mice were infected with HSV-1 strain F
      following corneal scarification. Clinical severity of keratitis was evaluated
      using slit-lamp biomicroscopy. Histologic severity of keratitis was determined by
      light microscopic evaluation and by computerized morphometry. Ocular viral
      replication was measured via plaque assay. RESULTS: Clinical lesions of stromal
      keratitis were more severe at 17 and 23 days post infection in Hox A5 transgenic
      mice than in wildtype mice. Histological evaluation and morphometric analysis
      confirmed that keratitis lesions were more severe in the transgenic mice. HSV-1
      replication was approximately100-fold greater in the corneas of transgenic mice
      than in wildtype mice. CONCLUSIONS: Our results demonstrate that a host gene (Hox
      A5) can increase ocular replication of HSV-1 and alter the pathogenesis of
      herpetic stromal keratitis.

PMID- 12045894
TI  - Chloride dependent intracellular pH effects of external ATP in cultured human non
      pigmented ciliary body epithelium.
AB  - PURPOSE: To examine the effects of extracellular adenosine 5-triphosphate (ATP)
      on intracellular pH ([pH](i)) in cultured human non-pigmented ciliary body
      epithelium (HNPE). METHODS: Intracellular pH was measured using
      spectrofluorescence video microscopy in isolated HNPE cells loaded with the cell
      permeable acetoxymethyl ester form of the fluorescent probe BCECF. RESULTS: In
      5%CO(2)/HCO(3)(-) buffered Ringer's the resting [pH](i) was 7.25 +/- 0.006 (mean
      +/- SEM). Application of 10 microM ATP significantly decreased [pH](i) to 7.00 +/
      0.007 (P < 10(-5), n = 14). In the presence of 1 mM suramin, a P(2) receptor
      inhibitor, this process was significantly blocked. This [pH](i) effect required
      the presence of Cl(-) and was significantly inhibited by 0.1 mM
      diisothiocyanatostilbene-2-2'-disulfonic acid or acetazolamide (500 microM),
      indicating the involvement of a Cl(-)/HCO(3)( +) exchange mechanism. This
      response exhibited little dependence on external Na(+) and remained unaffected by
      the addition of the Na(+)/H( +) exchanger inhibitor amiloride (1 mM). Clamping
      intracellular calcium levels by incubation in the cell permeable calcium
      chelator, the acetoxymethyl ester form of BAPTA (100 microM) in low extracellular
      calcium solution (pCa9) did not affect the ATP-induced [pH](i) signal. In
      addition, the vacuolar H(+)-ATPase (V-ATPase) inhibitor, bafilomycin A(1) (1
      microM), failed to alter the [pH](i) transient. CONCLUSION: We have demonstrated
      that extracellular ATP leads to a sustained increase in [H(+)](i) in HNPE cells
      via a purinergic receptor activated pathway which is independent of the
      intracellular calcium signaling system. This study demonstrates that the ATP
      induced [pH]( i) transient is mediated through an upregulation in Cl(-)/HCO( 3)(
      ) exchange across the plasmamembrane in HNPE cells.

PMID- 12045895
TI  - Extracellular ATP effects on calcium signaling in cultured human non-pigmented
      ciliary body epithelium.
AB  - PURPOSE: To determine the effects of extracellular ATP on calcium signaling in
      cultured human non-pigmented ciliary body epithelium (HNPE). METHODS:
      Intracellular calcium (Ca(2+)(i)) was measured using spectrofluorescence video
      microscopy in isolated HNPE cells loaded with the fluorescent dye Fura-2.
      RESULTS: Nucleotides caused a transient oscillatory increase in Ca(2+)(i) with a
      potency order of ATP = UTP > ADP > AMP> alpha,beta-methylene-ATP. Treatment with
      thapsigargin (100 nM), an inhibitor of endoplasmic Ca(2+)-ATPase pumps, produced
      a sustained increase in Ca(2+)(i). Subsequent exposure to ATP caused a rapid
      reduction in Ca(2+)(i) and this effect was reduced by pre-exposure to vanadate
      and to a lesser extent in sodium free solution. Prolonged exposure to ATP in the
      presence of thapsigargin caused a transient spike increase in Ca(2+)(i) which was
      prevented by exposure to low extracellular Ca(2+) (1 nmol/l), verapamil,
      nifedipine or the microfilament disrupting agent, cytochalasin B. CONCLUSIONS:
      These results provide evidence for ATP mobilisation of Ca(2+) from intracellular
      stores via P2Y2 receptor activation in HNPE cells. ATP also primarily activates a
      vanadate-sensitive Ca(2+ )-ATPase pump, in addition to having a smaller effect on
      the Na( +)/ Ca(2+) exchanger in terminating the calcium signal. Capacitative
      calcium entry, possibly via an L-type Ca(2+) channel, is implicated in generating
      a calcium signal following emptying of intracellular stores and is sensitive to
      cytoskeleton disruption. ATP can thus regulate a potent intracellular signal for
      secretion, suggest-ing that purinergic receptors may provide a therapeutic target
      in glaucoma.

PMID- 12045896
TI  - Noradrenaline receptor-mediated potentiation of caffeine-induced Ca( 2+)
      activated K(+) currents in bovine ciliary muscle cells.
AB  - PURPOSE: Adrenoceptor-mediated modulation of a caffeine (CAF)-induced [Ca(2+)](i)
      elevation and resulting Ca(2+)-activated K(+) current (I(CAF)) in bovine ciliary
      muscle (CM) cells were investigated. METHODS: The nystatin-perforated patch clamp
      technique for the measurement of membrane currents and a microscope based fura-2
      fluorescence imaging of [Ca(2+)](i) were applied to CM cells freshly dissociated
      with collagenase and identified with smooth muscle-specific alpha-isoactin.
      RESULTS: Under voltage-clamped conditions, noradrenaline (NA) potentiated I(CAF)
      in a NA concentration-dependent manner without producing current responses to NA
      when NA was applied alone. NA-induced potentiation of I(CAF) occurred within 20
      sec after the application of NA, while the NA-potentiated I(CAF) gradually
      recovered to the control level within 30 min after removal of NA. Despite the
      little current response to NA applied alone, NA elicited a [Ca(2+)](i) elevation
      in a manner similar to that induced by CAF although the NA-induced [Ca(2+ )](i)
      elevation was smaller than the CAF-induced [Ca(2+ )](i) elevation. In contrast to
      the significant potentiation of I(CAF) with NA, NA produced little potentiation
      of the CAF-induced [Ca(2+)](i) elevation. The NA-induced potentiation of I( CAF)
      was antagonized by an alpha(1) adrenoceptor antagonist, prazosin. Neither
      clonidine nor isoproterenol had an effect on I(CAF), suggesting that alpha(2) and
      beta adrenoceptor are not involved in the response to NA. CONCLUSIONS: These
      results suggest that NA potentiates I( CAF) via alpha(1) adrenoceptor activation
      and that the NA-induced potentiation occurs at Ca(2+)-activated K(+) channels but
      not CAF-induced Ca(2+) releasing sites.

PMID- 12045897
TI  - Collagens XII and XIV (FACITs) in capsular opacification and in cultured lens
      epithelial cells.
AB  - PURPOSE: We previously reported that extracellular matrix (ECM) accumulation in
      human capsular opacification included collagen types I, III, IV, V, and VI. To
      further characterize the ECM in capsular opacification we performed
      immunohistochemistry to localize collagen types XII and XIV (fibril-associated
      collagens with interrupted triple helices, or FACITs) in specimens of human
      capsular opacification and in cultures of bovine lens epithelial cells (LECs).
      METHODS: Cryosections and paraffin sections of human capsular opacification
      specimens or uninjured lens capsules, as well as cultured bovine LECs, were
      processed for immunohistochemistry using antibodies against collagen types I to
      VI, XII, and XIV. A rat crystalline lens was punctured through the central cornea
      and the eye was processed for immunohistochemistry for FACITs after healing
      intervals. RESULTS: In the absence of injury human LECs were unstained for
      FACITs, but as early as 10 days after operation, LECs in healing capsules were
      immunoreactive. Collagen types I, III, IV, V, and VI were also detected. ECM
      deposited in confluent LEC cultures stained for FACITs. Normal rat LECs were not
      stained for FACITs, but ECM accumulated in injured lens stained for them.
      CONCLUSIONS: LECs up-regulate FACITs during post-opera-tive healing. FACITs, as
      well as other collagen types, are deposited in ECM in healing injured rat lens,
      in human capsular opacification and in LEC cultures. ECM components may regulate
      LEC behavior during postoperative healing.

PMID- 12045902
TI  - Oculopharyngeal muscular dystrophy: What's new?
AB  - The authors place autosomal dominant oculopharyngeal muscular dystrophy in a
      historical perspective, look at the genealogy involved, and review the genetic
      studies. In addition to summarizing what happens at the histopathological level,
      they examine the clinical characteristics of this late-onset dystrophy. Based on
      this knowledge, they try to present their rationale for the surgical treatment of
      the eyelid ptosis, taking into account that this disease is progressive and that
      treatment should be planned for the lifetime of the patient. Three representative
      cases are illustrated. 

PMID- 12045898
TI  - Advanced glycation end products in Descemet's membrane and their effect on
      corneal endothelial cell.
AB  - PURPOSE: [corrected] The purpose of this study was to evaluate the effect of
      advanced glycation end products (AGEs) in Descemet's membrane on the attachment
      and spreading of the corneal endothelial cells. METHODS: An anti-AGEs monoclonal
      antibody (6D12), which recognizes a N(epsilon)-carboxymethyl lysine (CML)-protein
      adduct as an epitope, was used for immunohistochemistry and enzyme-linked
      immunosorbent assay (ELISA). Fresh bovine Descemet's membrane was incubated for 4
      weeks in the buffered solution with 500 mM of glucose-6-phosphate (G-6-P). In the
      incubated Descemet's membrane, the immunohistochemical localization of CML was
      examined. Type I collagen-, type IV collagen-, fibronectin-, or laminin-coated 96
      well plates were glycated by G-6-P. The amount of CML was determined by ELISA
      using 6D12. Cultured bovine corneal endothelial cells were seeded onto glycated
      or non-glycated extracellular matrix (ECM) in 96-well plates and allowed to
      attach for 3 hours. The number and the surface area of the attached cells were
      examined. RESULTS: Immunoreactivity to CML was detected in Descemet's membrane
      incubated in the buffered solution containing G-6-P. Glycation of fibronectin and
      laminin decreased the number and the surface area of the attached corneal
      endothelial cells. Aminoguanidine in the incubation mixture inhibited CML
      formation of ECM components and increased the number and the surface area of the
      attached corneal endothelial cells in a dose-dependent manner. CONCLUSIONS: AGE
      formation on fibronectin and laminin attenuated the attachment and spreading of
      the corneal endothelial cells. AGEs' formation in Descemet's membrane may be
      responsible for the corneal endothelial cell loss with aging and corneal
      endothelial abnormalities in diabetic patients

PMID- 12045903
TI  - Results of orbital decompression in Taiwan.
AB  - Orbital decompression was performed on 116 orbits with Graves' ophthalmopathy.
      The indications for decompression were dysthyroid optic neuropathy (DON),
      recalcitrant corneal exposure (EXP) and disfiguring exophthalmos (COS). All cases
      but one (in the DON group) had improved or unchanged vision. The average retinal
      sensitivity improvement in the DON group was 6.7 +/- 6.1 dB and 85% had a
      significant retinal sensitivity improvement (>5 dB). The average retroplacement
      effect was 4.4 +/- 2.1 mm and only five cases (7%) had postoperative asymmetry of
      more than 2 mm by Hertel's exophthalmometry. The most frequent sequela was
      diplopia, which tended to occur in more severely myopathic eyes. In our series,
      21% (10/48 cases without preoperative diplopia) developed diplopia after
      decompressive surgery. Hypoglobus is another complication, noted in two cases,
      which was successfully repositioned. In conclusion, decompressive surgery is a
      safe and effective procedure to restore vision and reduce exophthalmos in Graves'
      ophthalmopathy. Careful evaluation of clinical parameters, individualization of
      surgical goals and intraoperative titration of the retroplacement effect are the
      key to optimal results. 

PMID- 12045904
TI  - Methylprednisolone pulse therapy for patients with dysthyroid optic neuropathy.
AB  - purpose 1) To test the short- and long-term efficacy of Methylprednisolone Pulse
      Therapy (MPT) for patients with Dysthyroid Optic Neuropathy (DON). 2) To assess
      possible side-effects of MPT. 3) To assess whether a delay in decompressive
      surgery would influence the visual outcome. study design Retrospective,
      uncontrolled. method The records of 62 consecutive patients with DON, who
      received MPT between 1994 and 2000, were evaluated with special attention for pre
      and post treatment ophthalmic and orthoptic parameters, Clinical Activity Score
      (CAS), visual fields and visual evoked potentials, and treatment complications.
      DON-patients were hospitalized and received four times 500 mg methylprednisolone
      intravenously. Immediately afterwards they were treated with oral prednisone
      (maximal dose 60 mg) and/or orbital irradiation (10 times 2 Gy). Evaluation was
      done one day after the last bolus (T1) and when the orbitopathy had been stable
      for at least six months (T2). results Visual acuity, proptosis, elevation and CAS
      all improved significantly at T1, whereas the lid aperture did not change. At T2,
      24 out 62 (39%) DON-patients were stable with normal vision. The other 38 (61%)
      had undergone orbital decompression because of persistent or recurrent DON within
      one week to six months after MPT. Final visual acuity in the whole group (121
      eyes) was less than 0.1 in 3 eyes, between 0.1 and 0.5 in 17 and more than 0.5 in
      101 eyes. Treatment complications were: pylorus ulcer (n = 1), increased
      osteoporosis (n = 1), abcess formation (n = 1), and increase in insulin dosage (n
      = 1). conclusions 1) MPT is efficious as emergency treatment. 2) One-third of DON
      patients are spared decompressive surgery. 3) MPT causes only rare and no serious
      side-effects. 4) The final visual outcome after MPT and orbital decompression is
      comparable to the results of immediate decompression. 

PMID- 12045905
TI  - Graves' ophthalmopathy through the eyes of the patient: A state of the art on
      health-related quality of life assessment.
AB  - The negative impact of the visual limitations and disfigurement associated with
      Graves' ophthalmopathy (GO) for a patient's daily life has always been
      acknowledged in clinical practice. However, only recently have the effects of GO
      on health-related quality of life (HRQL) been quantified using validated
      questionnaires. In this article, a state of the art is presented on the aims,
      methodology and application of HRQL assessment in GO research. HRQL assessment is
      important in cross-sectional studies aimed at describing the severity of GO on
      multiple outcome levels, including the impact of GO on patients' daily
      functioning and perception of health in general, and in longitudinal studies
      aimed at the evaluation of treatment efficacy or comparison of the effects of
      different treatments on HRQL. Only a few studies have measured the effects of GO
      on HRQL directly. Patients with GO have a relatively low HRQL, not only in the
      period that they are diagnosed and treated for the disease, but their low HRQL
      persists even many years after the final treatment. Because the current therapies
      for GO are primarily directed at improving (visual) functioning and appearance,
      these treatments should be evaluated for their effectiveness on HRQL outcomes. At
      the moment, the recently developed GO-QOL questionnaire is the only validated
      disease-specific instrument available to measure HRQL in patients with GO. The GO
      QOL is recommended as an instrument to measure GO treatment effects on HRQL. 

PMID- 12045906
TI  - Hemorrhagic cavernoma or ruptured dermoid of the orbit: Diagnosis with MRI.
AB  - MRI is a useful tool to study space-occupying lesions of the orbit. We present
      two cases of intraorbital lesions that were found to be a hemorrhagic cavernous
      hemangioma and a ruptured dermoid, respectively. The difficulties in arriving at
      the diagnosis of these rare entities with MRI are discussed. In general, dermoids
      are characterized by a peripheral, extra-conal location in the immediate vicinity
      of an orbital suture, while cavernous hemangiomas tend to be intraconal.
      Secondary complications of both entities, such as hemorrhage or rupture, may
      alter the characteristic MRI signal patterns found in uncomplicated lesions.
      Inflammatory reactions may be observed. The signal of the fatty dermoid and the
      hemorrhagic part of a cavernoma are both of high intensity on the T1-weighted
      images, and this may lead to diagnostic difficulties. 

PMID- 12045907
TI  - Multifocal Rosai Dorfman disease of periorbital tissues spanning 15 years - a
      case report.
AB  - The authors report a rare case of Rosai Dorfman disease with multifocal
      involvement of periorbital tissues, beginning in a young girl at the age of 3 and
      spanning 15 years. Surgical treatment was successful. 

PMID- 12045908
TI  - The pathogenesis and treatment of lacrimal obstruction: The value of lacrimal sac
      and bone analysis.
AB  - INTRODUCTION. The cause of primary acquired nasolacrimal duct obstruction (NLDO)
      has not been fully elucidated. In an attempt to determine the role of an
      inflammatory etiology, the pathology of nasolacrimal sac and bone specimens was
      assessed and correlated with clinical lacrimal variables. MATERIALS AND METHODS.
      Lacrimal sac and bone tissues from patients with known NLDO were sampled at the
      time of external dacryocystorhinostomy (DCR). Histopathological analysis was
      carried out to determine the presence and degree of inflammatory changes present
      in the tissues, and to correlate them with the clinical presentation. RESULTS. Of
      104 cases analyzed, bony inflammatory changes were seen in 14% and lacrimal sac
      inflammatory changes in 94%. All cases of bony inflammation had accompanying
      lacrimal sac inflammation. The inflammatory changes were independent of the
      following variables: gender, duration of symptoms, a history of dacryocystitis,
      the presence of a lacrimal sac mucocele, the location of obstruction, and the
      presence of lacrimal sac calculi. CONCLUSIONS. Inflammatory changes are almost
      invariably present in all patients with NLDO. Its occurrence in bone is probably
      secondary to lacrimal sac inflammation. Although attempts are made to perform DCR
      surgery only in the absence of lacrimal sac inflammation, almost all cases
      exhibit subclinical inflammation. This may suggest that bypassing this 'critical
      area' of the sac-duct junction, as in a dacryocystorhinostomy, would be more
      reasonable than to re-canalize through an inflammatory obstruction. 

PMID- 12045909
TI  - Lacrimal drainage capacity and symptomatic improvement after
      dacryocystorhinostomy in adults presenting with patent lacrimal drainage systems.
AB  - AIM. To determine the rate of symptomatic improvement after dacryocystorhinostomy
      (DCR) in patients with epiphora and insignificant obstruction to preoperative
      lacrimal syringing, and to measure the conductance of the postoperative lacrimal
      drainage anastomosis. METHODS. Retrospective cohort study of patients with
      symptomatic epiphora and patent tear ducts, with at least two-year follow-up
      after DCR. Patients underwent structured telephone interview together with
      clinical examination for lacrimal drainage capacity using the saline drop
      test.(1) RESULTS. Thirty-seven of 383 adult patients having had DCR were noted to
      have patent tear ducts at preoperative examination. Ten patients with previous
      surgery were excluded and two other patients were excluded because of other
      factors contributory to epiphora. Of the remaining 25 patients, 22 (aged 35-75
      years at surgery; median 56 years) underwent a structured telephone interview: Of
      the 13 (60%) who felt that symptoms had improved, 9 (41%) were relieved of indoor
      epiphora and 11 (50%) thought the procedure was an overall success. Seventeen
      patients underwent clinical examination. The lacrimal drainage anastomosis was
      patent in all patients and the saline drop test result was well within the normal
      range in 3/4 patients who had persistent indoor epiphora. CONCLUSION. Of patients
      with epiphora due to minor nasolacrimal duct stenosis, open DCR produces a marked
      improvement or cure of symptoms in 50%. The lacrimal drainage capacity was well
      within the normal range in 3/4 patients with persistent postoperative lacrimal
      symptoms, suggesting that other factors (such as hypersecretion) may be
      significant in this group of patients with 'functional block'. 

PMID- 12045910
TI  - The use of the fluorescein disappearance test in the management of childhood
      epiphora.
AB  - PURPOSE. The fluorescein disappearance test (FDT) is reported to be an objective
      measure of lacrimal outflow in congenital non-canalisation of the nasolacrimal
      system. We introduced FDT into our evaluation of children with epiphora to
      investigate its sensitivity/specificity with regard to symptoms in a prospective
      study. We also examined the FDT against findings at syringing and probing (S&P)
      and persistence or resolution of symptoms on follow-up. METHODS. Over a period of
      16 months, 88 consecutive children (median age 12 months; range 2.5-192) with
      epiphora were reviewed and FDT measured at 5 and 10 minutes; 66 FDT were
      evaluated for inter-observer variation in a masked fashion. S&P were scheduled on
      the basis of symptoms, abnormal FDT and age "1 year. Normal FDT prompted review.
      Younger children were observed for natural history and possible resolution with
      repeat FDT. Equivocal symptoms and normal FDT initiated discharge and telephone
      review. RESULTS. Inter-observer correlation coefficient = 0.86.
      Sensitivity/specificity of FDT was 76/76% at 5 minutes and 63/89% at 10 minutes,
      respectively. In patients under 1 year of age undergoing follow-up (29 patients;
      38 eyes) FDT at 10 minutes correctly predicted persistence of symptoms in 65% and
      resolution in 66% of eyes (follow-up 3-14 months; mean 6); 23 patients (mean age
      27 months; range 12-72) underwent S&P with positive surgical findings in 20
      (87%). On review, symptoms had improved in 64% eyes (20/31). CONCLUSION. FDT at 5
      minutes is an objective measure of symptoms with high inter-observer agreement
      and agreement with surgical findings. FDT read at 10 minutes may be useful to
      indicate the persistence or resolution of symptoms and guide patient management. 

PMID- 12045911
TI  - Mini Monoka silicone monocanalicular lacrimal stents: Subjective and objective
      outcomes.
AB  - BACKGROUND. Canalicular injuries and anomalies are relatively common. Despite
      this, controversy still exists regarding the indications for surgery and best
      surgical methods. The most favourable intervention would be one that is simple,
      associated with a high level of subjective and objective outcome, and does not
      threaten the uninjured or unaffected part of the lacrimal drainage system. This
      study assesses outcomes of intervention with the Mini Monoka silicone
      monocanalicular lacrimal stent. METHOD. A single cohort, hospital-based study
      with retrospective and prospective components. Participants were all identifiable
      patients at Bristol Eye Hospital in whom the Mini Monoka silicone monocanalicular
      stent was used for any indication. Retrospective analysis of patient records for
      all related pre-operative, operative and postoperative data was performed.
      Prospective analysis of subjective outcome via confidential patient questionnaire
      and objective outcome via clinical examination was performed. RESULTS. Complete
      data were obtainable in 13 patients (14 canaliculi) of the identified 22 patients
      (23 canaliculi). Follow-up was from 12 to 70 months (mean 39 months). A high
      level of subjective outcome was noted with no patients experiencing significant
      or disabling symptoms. In terms of objective outcome, 79% achieved canalicular
      patency. The main complications with this technique were premature stent loss
      (29%) and stent migration (14%). CONCLUSIONS. The Mini Monoka monocanalicular
      stent is a safe, effective and simple surgical technique that, unlike
      bicanalicular procedures, does not threaten the uninjured / unaffected part of
      the lacrimal drainage system. 

PMID- 12045912
TI  - Retrograde dacryocystography (RDC) utilizing a round-tipped needle.
AB  - Because the application of conventional anterograde dacryocystography has been
      restricted in cases with an intact lacrimal punctum, the indications are rather
      limited. The authors developed a new method for retrograde dacryocystography
      (RDC) using a hand-made round-tipped needle inserted directly into the orifice of
      the nasolacrimal duct. A 60 mm long aluminum tube (3 mm in diameter) was used to
      prepare the round-tipped needle. The distal portion of the tube was bent to an
      angle of about 80 degrees. The tip was then coated with synthetic resin adhesive
      to make it round. Following the insertion of the round-tipped needle directly
      into the inferior meatus, the tip was moved back and forth to find the orifice
      without visual observation. The complete insertion of the tip of the needle into
      the nasolacrimal duct was recognized by a fixed sensation of the tip. Contrast
      medium was then injected, and PA radiography was carried out. In the present
      paper, the authors report the usefulness of RDC, which is applicable even in
      cases of injury or obstruction in the upper lacrimal system. In 16 of 20
      patients, the quality of the RDC images was judged as excellent. RDC can be
      carried out within a few seconds after acquiring the technical skills, and is
      thought to be a useful method, especially in cases of upper lacrimal injury. 

PMID- 12045913
TI  - Periocular Mohs micrographic surgery: Results of a dual-site day-surgery service.
AB  - PURPOSE. To assess the feasibility of day-surgery Mohs Micrographic Surgery (MMS)
      at dual sites. METHODS. MMS now has an established position for the management of
      skin tumour removal. The literature reports excellent results in terms of tissue
      preservation, complete tumour excision and recurrence rate. MMS involves an
      initial stage undertaken by dermatologists. The subsequent reconstructive phase
      can be undertaken either by the dermatologist or by an oculoplastic surgeon in
      cases of extensive defects. In the latter cases, special expertise is needed in
      order to achieve satisfactory cosmetic results. Centres offering MMS are few and
      are usually located in tertiary referral hospitals. In a large city of 12 million
      inhabitants like London there is only one centre offering MMS on the National
      Health Scheme. We have set up a dual-site day-surgery service since 1997, whereby
      a Mohs trained dermatologist in the first unit undertakes the initial ablative
      stage. The patient is then transferred to the second location, which is
      approximately three miles away; a trained oculoplastic surgeon then undertakes
      the reconstruction the same day. Rarely, defects are deemed too large for
      reconstruction and the patient discharged on the same day; patients are then
      admitted as inpatients for reconstruction the following day with oculoplastic,
      plastic, craniofacial and facio-maxillary services at hand. RESULTS. To date we
      have operated on 59 patients for removal of basal cell carcinomas (BCC). All
      patients had a biopsy-proven diagnosis of BCC before being referred to the
      dermatologist. Following liaison with the Dermatology Unit, surgery was scheduled
      so that the reconstruction could be undertaken in the Oculoplastic Unit at the
      second hospital on the same day. All patients' defects were reconstructed
      successfully. With the longest follow-up being 39 months so far, tumour
      recurrence has been 0%. CONCLUSIONS. A dual-site day-surgery service seems to be
      a feasible option where a MMS dermatologist is not present onsite. The logistic
      problem can be easily overcome with a proper liaison between the departments. A
      dual-site day-surgery MMS service provides a superior service compared with the 2
      mm tumour-free margin excision and delayed surgical repair following histological
      examination advocated by other authors where MMS is not available on site. It is
      only with MMS that one can ensure complete tumour excision. Day-surgery is the
      preferred choice, both for patients and for financial considerations. We would
      therefore support the establishment of dual-site day-surgery MMS services where
      the reconstruction is undertaken in hospitals located away from the MMS
      dermatology unit, provided close collaboration exists between the two units to
      ensure the smooth transfer of patients. 

PMID- 12045914
TI  - Correction of lower eyelid retraction with high density porous polyethylene: The
      Medpor((R)) Lower Eyelid Spacer.
AB  - PURPOSE. To describe the use of a new alloplastic implant for the correction of
      complex lower eyelid retraction. METHODS. A retrospective review of patient
      charts and photographs was performed to evaluate the efficacy of the first 50
      porous polyethylene lower eyelid spacers (LES) used in the correction of complex
      eyelid retraction. RESULTS. Fifty LES were implanted in 38 patients. Follow-up
      ranged from 18 to 32 months. The average number of surgical procedures attempted
      for eyelid retraction repair prior to referral to our practice and implantation
      of the LES was 5, range 0 to 16. After LES implantation, all patients had
      improvement of their lower eyelid retraction. Three LES implants were revised for
      eyelid contour deformity ('lateral winging') and one for exposure through the
      anterior eyelid margin. In two cases, full-thickness skin grafts were placed
      directly over the porous implants with good success. DISCUSSION. Lower eyelid
      spacers (LES) constructed of porous polyethylene provide a rigid, bio-integrated
      support for eyelids with severe malposition that are recalcitrant to other
      corrective efforts. 

PMID- 12045915
TI  - Facial reanimation surgery utilizing the Mitek anchor system: A case report.
AB  - A flaccid hemi-face is frequently the most noticeable and cosmetically
      unacceptable consequence of facial nerve palsy, whether due to trauma, Bell's
      palsy or other etiologies. A variety of face-lift and reanimation techniques have
      been utilized in the past, but with time, these frequently require further
      surgery. We describe the use of Mitek (Norwood, MA) suture anchors for cheek
      resuspension in a patient with facial palsy. This system is composed of a drill
      guide, drill, inserter, and anchor. Although the titanium alloy anchors come in
      multiple sizes, the Mini GII Anchor is typically most appropriate for use in
      facial procedures. The actual size of the Mini GII Anchor is 1.8 mm in diameter
      and 5.4 mm in length. Two small arched prongs extend from the body of the anchor,
      and an eyelet at the superior surface is used for suture placement. When placed
      into a pre-drilled hole with the insertion tool, the prongs extend, effectively
      fixing the anchor in place. The drill guide protects adjacent soft tissues during
      the drilling process and allows drilling to a predetermined fixed depth. Sutures
      attached to the anchor may then be used for soft tissue fixation to bone. 

PMID- 12045916
TI  - Orbital involvement as the first manifestation in classic Wegener's
      granulomatosis.
AB  - Wegener's granulomatosis (WG) is a chronic, focal, necrotizing granulomatous
      angiitis, which mainly affects the upper respiratory tract, the lungs and the
      kidneys. We present the case of a 26-year-old female patient complaining of pain
      and increasing swelling of the upper right eyelid with exophthalmos and diplopia
      as the first manifestation of a classic WG. Computer tomography revealed a
      homogeneous tumor arising from the right lacrimal gland. Chest x-ray revealed a
      tumor of the right lung. Microhematuria disclosed a slight renal involvement.
      Positive ANCA titer and C-ANCA anti-PR3, as well as a positive lung biopsy,
      confirmed the diagnosis of WG. Treatment with prednisone and cyclophosphamide was
      initiated. One year later, the patient's condition was good, and the
      ophthalmological examination was normal. WG should be considered in the
      differential diagnosis of an orbital tumor. In some rare cases, orbital disease
      can be the first clinical manifestation of the classic form of WG. 

PMID- 12045917
TI  - Rosai-Dorfman syndrome affecting the lacrimal gland.
AB  - This is a case report of Rosai-Dorfman syndrome in a 36-year-old Caucasian male,
      involving the lacrimal gland, cervical lymph nodes, nasal and sinusal mucosa. It
      was successfully treated with appropriate immunosuppression. He had initially
      presented to the ENT surgeon with nasal and sinusal mucosal thickening and
      bleeding. Cervical lymph node biopsy produced a histological diagnosis compatible
      with Rosai-Dorfman disease. Later he developed an acute red proptotic eye. He had
      severe proptosis due to an enlarged lacrimal gland. He refused surgical excision
      of the tumour, which is suggested if there is an ocular adnexal involvement.
      Conservative treatment with systemic steroid resulted in the resolution of
      lacrimal gland swelling, nasal sinusal mucosal thickening and cervical
      lymphadenopathy. Previous studies have shown that patients with Rosai-Dorfman
      syndrome are often black males1 and require surgery. 

PMID- 12045918
TI  - Orbital streptococcal gangrene and AIDS.
AB  - Streptococcal gangrene can present to the ophthalmologist as a fulminant orbital
      cellulitis involving the eyelids, globe and orbit. Compromised vision is likely,
      as well as serious systemic illness and death. It commonly affects young and
      healthy hosts and, prior to this presentation, has never been reported in a
      patient with HIV infection. We studied a case of streptococcal gangrene of the
      eyelids and orbit in a patient with AIDS. The infection was treated with
      debridement and intravenous antibiotics, and showed eventual improvement with the
      exception of visual function. A biopsy of the lesion exhibited extensive soft
      tissue necrosis with a predilection for blood vessels, resulting in thrombosis
      and infarction. Cultures grew out heavy group A beta-hemolytic Streptococcus.
      This case illustrates that streptococcal gangrene can occur with HIV, although to
      date this combination has been rare. Early diagnosis is crucial and includes
      recognition of incipient cutaneous, histopathological and anterior segment
      ischemia signs. 

PMID- 12045919
TI  - Role of the lower lid retractors in involutional ectropion repair.
AB  - AIM. To outline the role of the lower lid retractors in correction of
      involutional ectropion. METHODS. Eight eyelids with a tarsal ectropion were
      included in the study. Clinical clues to help identify weakness of the lower lid
      retractors were documented. A transconjunctival lower lid retractor reattachment
      with concommitant correction of horizontal lid laxity and lamellar dissociation
      was performed. RESULTS. Stable eyelid position was obtained in 7 of the 8 cases.
      One case had a lateral ectropion due to a wound dehiscence. CONCLUSIONS. This
      small study helps better define the clinical presentations of retractor weakness
      and provides evidence of a systematic approach in correcting involutional
      ectropion. 

PMID- 12045920
TI  - Ptosis forceps with a protected lock: A new device in oculoplastic surgery.
AB  - The authors describe a new device for oculoplastic surgery, a so-called ptosis
      forceps with a protected lock, which greatly facilitates dissection of the
      levator muscle in ptosis operations as well as in levator recession procedures.
      The instrument consists of an inferior part, including two grooved atraumatic
      flat jaws, and a superior part, including a bulging rough area and a smooth
      tapered tip. The original feature of this new device is its hidden lock
      mechanism, located between the two bulging parts of the forceps, in such a way as
      to free the instrument(1)s outer surface, thus making grasping and release of the
      levator muscle easier during surgery. 

PMID- 12045921
TI  - Cicatricial ectropion in progressive skin diseases.
AB  - PURPOSE. To report the clinical course, patient care and treatment of cicatricial
      ectropion in patients with progressive skin diseases. METHOD. Review and photo
      series of three typical cases, which were followed for up to 10 years. RESULTS.
      In certain severe progressive skin diseases, tissue shrinkage may progress
      permanently. The soft lid tissue cannot withstand the forces of vertical lid
      traction. As a result, recurrent ectropion occurs. Patients with lamellar
      ichthyosis and with eruptive Grzybowski-type keratoacanthoma were followed for up
      to 10 years. Free skin grafts of severely involved donor skin were repeatedly
      transplanted to the lids. The lid margins were fixed by traction sutures in order
      to spread out the wound and to allow rapid vascular ingrowth and undisturbed
      healing. In this way, early wound contracture could be prevented. Nevertheless,
      follow-up revealed progressive shrinkage of the transplanted lid skin. Eversion
      of the lacrimal punctum was the first sign of progression. Epiphora was the
      leading complaint of the patients. Bacterial superinfection of the deepened
      lacrimal lake was more frequent in advanced ectropion. CONCLUSION. Patients
      should understand the natural history of their disease in order to accept
      multiple surgical procedures. Ectropion should be re-operated in time in order to
      reduce epiphora, to prevent corneal complications, and to avoid metaplasia and
      keratinization of the conjunctiva and thickening of the lid margin. The
      elasticity of the lid skin should be improved pharmacologically and by increasing
      the relative humidity of the home environment, especially in winter. Consistent
      vertical lid massage can delay recurrence. 

PMID- 12045922
TI  - Orbicularis oculi muscle stripping and tarsal fixation for recurrent entropion.
AB  - This prospective study highlights the result of a new technique for correction of
      recurrent lower lid entropion. The technique was designed to address the
      aetiological factors involved based on the pre- and per-operative findings.
      MATERIAL AND METHODS. 37 eyelids of 31 consecutive patients with recurrent
      entropion were enrolled. Under local anaesthesia, a horizontal incision was made
      at the lower border of the tarsus, involving the total width of the lower eyelid.
      Anterior lamellar (skin and orbicularis oculi muscle - OOM) inferior to the
      incision was dissected towards the orbital rim. An ellipse of the excess
      overriding OOM and overlying skin inferior to the incision was excised. The OOM
      was fixed to the lower border of the tarsus with three to four 6/0 Vicryl
      subcutaneous sutures. Skin was repaired with 6/0 silk sutures, which were removed
      five days post-operatively. Five cases underwent horizontal lid shortening and 15
      had preaponeurosis fat sculpting in addition. RESULTS. 37 procedures were
      performed on 31 patients (23 M & 8 F). The mean age was 76.5 yrs. (range 63-90).
      The patients had had one to four (mean = 1.7) previous surgeries. All patients
      had OOM override. Fifteen had significant preaponeurosis fat prolapse. Lower lid
      laxity was not identified in all cases, in some due to previous lid surgery.
      There was no evidence of lower lid retractor laxity in the majority of cases.
      After a mean follow-up time of 18 months (5-36) there were three recurrences. One
      underwent further tarsal fixation and the other two had horizontal lid shortening
      with a favourable outcome. CONCLUSIONS. Excision of overriding OOM and tarsal
      fixation for recurrent entropion is simple and effective. Its success is due to
      direct tackling of the aetiological factors. 

PMID- 12045923
TI  - Transorbital craniotomy through a suprabrow approach: A case series.
AB  - Six cases of posterior orbital mass lesions are described in which a suprabrow
      approach was utilized for transorbital craniotomy. This technique offers several
      advantages over traditional supraorbital and transcranial approaches to deep
      orbital tumors. The results were anatomically and cosmetically excellent in all
      cases. The surgical technique for transorbital craniotomy, along with its
      advantages and potential complications, are explained in detail. The clinical
      presentation, radiological features of the lesions, postoperative outcome, and
      complications are discussed. 

PMID- 12045924
TI  - Primary orbital lymphoma.
AB  - BACKGROUND/AIMS. Localized orbital non-Hodgkin's lymphoma is a rare form of
      extranodal lymphoma. The aim of this study was to evaluate the outcome of 48
      patients presenting with stage I-E non-Hodgkin's lymphoma (NHL). METHODS. Out of
      118 charts of patients with lymphoproliferative lesions, those of 48 patients
      with stage I-E orbital lymphoma seen over a 22-year period from 1977 through 1999
      were reviewed. RESULTS. Twenty-five patients were male and 23 were female. Their
      mean age was 58.7 (12-85) years. The mass was localized inside the orbit in 37
      cases and in the lacrimal gland region in 11 cases; bilateral involvement was
      observed in two cases. The duration of the symptoms at the time of presentation
      ranged from 10 days to 10 years with a mean duration of 18 months. The 24 cases
      with low-grade lymphoma are all alive without disease, whatever therapeutic
      approach was performed (biopsy, radiotherapy, chemotherapy). In intermediate and
      high-grade NHL the rate of recurrence after chemotherapy has been 50% and 33%,
      respectively, compared to 75% and 50% after biopsy alone and 75% after
      radiotherapy (not administered in high-grade forms). CONCLUSION. The therapeutic
      approach to localized orbital non-Hodgkin's lymphoma must take the histologic
      grading into consideration. The 24 cases with low-grade lymphoma had a good
      prognosis. The 17 cases with the intermediate-grade form and the 7 cases with the
      high-grade form had a better prognosis when treated with chemotherapy. 

PMID- 12045925
TI  - Maximal levator resection in the treatment of unilateral congenital ptosis with
      poor levator function.
AB  - From 1994 to 1999, 1121 operations for blepharoptosis were performed in our
      department on 987 patients. In 44 cases we found a moderate to severe congenital
      ptosis with a levator function of less than 2 mm. Until today, in such cases, it
      is recommended to use a frontalis suspension in order to elevate the upper
      eyelid. Unsatisfactory cosmetic results in facial expression and lack of skin
      fold are only a few of the disadvantages of this technique. In 1994, therefore,
      we decided to perform a maximal levator resection in the treatment of unilateral
      congenital ptosis with poor levator function. All children included in our study
      were younger than six years of age. The ptosis was moderate (2-4 mm) in 36/44 and
      severe (>4 mm) in 8/44 cases. The levator function was less than 2 mm. Complete
      transsection of the medial and lateral horn of the levator aponeurosis under
      preservation of the Whitnall ligament is the most important surgical step in
      mobilizing the levator muscle. A satisfactory eyelid elevation (generally
      considered to be a difference of less than 1 mm between both eyelid fissures) was
      achieved in 36/44 cases. Our results indicate that, in contrast to established
      practice, maximal levator resection is the treatment of choice for congenital
      ptosis with poor levator function. 

PMID- 12045926
TI  - Treatment of primary lymphoma of the lacrimal gland by surgical excision alone: A
      5-year follow-up study.
AB  - PURPOSE. To evaluate the long-term efficacy of surgical excision alone in the
      treatment of non-Hodgkin(1)s lymphoma localized to the lacrimal gland. MATERIALS
      AND METHODS. Thirteen patients with primary lacrimal gland lymphoma were
      included. The presumptive diagnosis was based on: (1) The painless and relatively
      slow onset of unilateral lacrimal gland swelling, mostly in elderly adults; (2)
      The CT pattern of a soft tissue mass in the lacrimal gland region with defined
      margins and molds to the globe; (3) The negative results of systemic work-up. The
      involved lacrimal gland was excised via an anterior trans-septal approach in 12
      cases and by lateral canthotomy, upper cantholysis, and a trans-periosteal
      approach in one case. Following histopathologic confirmation of the diagnosis, no
      supplemental therapy was given. The patients were followed for a minimum of 5
      years (5-8 years). RESULTS. In all patients, the excised lacrimal gland lymphoma
      was firm, nodular and appeared encapsulated. The histologic subtypes of the
      excised masses were: low-grade lymphomas in 11 cases (7 small lymphocytic, 3
      plasmacytoid lymphocytic, 1 follicular small cleaved) and intermediate grade in 2
      cases (1 follicular large cell and 1 diffuse small cleaved). No evidence of local
      recurrence or systemic dissemination was reported during the follow-up period in
      any of the patients. CONCLUSIONS. Surgical excision of the tumor is a new
      curative technique for lymphoma localized to the lacrimal gland without any other
      orbital or systemic involvement. By this technique, orbital radiotherapy and its
      potential ocular complications can be avoided. However, more study is
      recommended. 

PMID- 12045927
TI  - The transnasal advancement flap: A technique for medial canthal area defects.
AB  - AIM. To illustrate an alternative technique for reconstructing defects in the
      medial canthal area following tumour removal. MATERIALS AND METHODS. Eight
      consecutive patients who underwent Mohs(1) micrographic surgery for removal of a
      basal cell carcinoma in the medial canthal area were prospectively recruited. An
      experienced dermatologist trained in Mohs(1) micrographic surgery removed the
      tumour, and subsequently an oculoplastic surgeon reconstructed the defect. An
      incision is made from the superior end of the defect superomedially towards the
      midline of the dorsum of the nose following one of the natural lines of the skin
      (spec name). The incision runs in arcuate fashion just medial to the eyebrow and
      then reaches the dorsum of the nose and extends on the contralateral aspect of
      the nose towards the medial canthal area. The skin is then undermined to free up
      the newly formed flap. The flap is advanced towards the lesion and fixed intra
      dermally with Vicryl Rapide(R) sutures to ensure anchoring into the concavity of
      the medial canthal region. The skin is then sutured with prolene sutures.
      RESULTS. The defects presented were oval or round in shape with diameters ranging
      from 0.5 to 2 cm. In all cases the transnasal flap covered the entire area and
      the defect was successfully reconstructed. Mean follow-up is 10.8 months (+/-4.5
      SD) (range 4-17 months); all patients had an excellent cosmetic result and were
      subjectively satisfied. CONCLUSIONS. The transnasal advancement flap seems to
      have some advantages over the usual reconstruction techniques in use to repair
      medium defects in the medial canthal area. These are the avoidance of vertical
      scars in the glabellar area, eyebrow hair is not transposed into the medial
      canthal area, the skin match is excellent, both in colour and thickness, and
      surgical scars are hidden within the natural lines of the nasal bridge. We
      advocate the use of this technique for all minor to medium skin defects. 

PMID- 12045928
TI  - Orbital rhabdomyosarcoma: Clinicopathologic correlation, management and follow-up
      in two newborns. A preliminary report.
AB  - Rhabdomyosarcoma (RMS) is the most common primary malignant tumor of the orbit in
      childhood. The average age of onset is around seven years. In the present paper,
      the authors present the clinical and radiological findings in two newborns with
      histopathologically confirmed orbital rhabdomyosarcoma. A review of the
      literature was also carried out. In both children, the first sign leading to a
      visit was a unilateral proptosis, without symptoms or any other sign. Both
      underwent a CT-scan and an MRI. Confirmation of the histology was made by an open
      sky biopsy. The children were first treated by chemotherapy but had incomplete
      resolution of the tumor after more than 11 months for the first case and 9 months
      for the second. Since the parents of both children refused exenteration,
      radiotherapy had to be resorted to because of the incomplete response to
      chemotherapy. Our therapeutic approach and the outcome of these two cases are
      discussed. 

PMID- 12045929
TI  - An indeterminate malignant soft-tissue tumour treated by exenteration.
AB  - PURPOSE. To present a case of malignant soft-tissue tumour, which has yet to be
      categorised despite review by an international panel of experts, and which was
      treated by exenteration. PATIENT & METHODS. A 15-year-old Caucasian girl
      presented with progressive, non-axial proptosis and diplopia. CT scan showed an
      extraconal mass in the supero-medial part of the orbit suggestive of a vascular
      neoplasm. After initial incisional biopsy, the pathology of the tumour was felt
      to be malignant but so unique that further tissue was required for
      classification/categorisation and that exenteration was the best way to proceed.
      RESULTS. Despite there being an adequate amount of tissue and opinions being
      sought from international experts, including the Children(1)s Soft Tissue Panel
      (of the United Kingdom), this tumour has yet to be categorised. Reports have
      suggested it to be anything from a malignant desmoplastic round-cell tumour or a
      synovial sarcoma to an epithelioid haemangioendothelioma, which is our current
      working diagnosis. CONCLUSION. This case is unique in that it has not been
      possible to classify the tumour. Categorisation is important in order to give a
      reasonably accurate prognosis to the patient. Exenteration was required to offer
      complete tumour excision and will hopefully prevent local recurrence and
      metastatic spread. 

PMID- 12045930
TI  - Exophthalmometric values in a normal Indian population.
AB  - PURPOSE. The purpose of this study was to establish a set of exophthalmometric
      values in a normal Indian population and to compute a regression equation for
      calculating these values. METHODS. Twenty-five-hundred clinically normal Indians
      of both sexes in the age group of 3-80 years, who did not have local or systemic
      disease likely to affect orbital or ocular structures, were enrolled in this
      study. Hertel's exophthalmometer was used to measure the degree of protrusion of
      the eyes. Statistical methods were used to calculate the mean values in the right
      and left eye in either sex and to compute a regression equation for calculating
      the exophthalmometric values. RESULTS. The range of exophthalmometric values in a
      normal Indian population aged 3-80 years was 7-19 mm for males and 7-21 mm for
      females. The exophthalmometric values were higher in the first decade, decreased
      in the second decade, and increased again in the third decade. They then remained
      stable for the next three to four decades. The peak was reached in the seventh
      decade in males and in the sixth decade in females. The lowest values in both
      sexes were attained in the eighth decade. The regression equations for the
      calculation of the exophthalmometric values are: In males for the right eye:
      Exophthalmometric value = 12.43 + 0.25 x age; In males for the left eye:
      Exophthalmometric value = 12.30 + 0.029 x age; In females for the right eye:
      Exophthalmometric value = 13.30 - 0.003 x age; In females for the left eye:
      Exophthalmometric value = 13.17 - 0.0003 x age. CONCLUSIONS. The trend of the
      normal exophthalmometric values for Indian subjects, by and large, was found to
      be similar to that quoted for other races. A knowledge of the normal values for
      this population subgroup can help clinicians in the early diagnosis and follow-up
      of patients with endocrine diseases, orbital tumors, craniofacial trauma and
      deformities and severe myopia. 

PMID- 12045931
TI  - Fine needle aspiration biopsy in orbital lesions.
AB  - PURPOSE. The study was performed to evaluate the efficacy of fine needle
      aspiration biopsy (FNAB) in orbital lesions. METHODS. Seventeen patients with
      orbital masses who had been fully investigated by non-invasive techniques
      participated in this study. FNAB was performed by standard technique, as an
      outpatient procedure, with ultrasound guidance in lesions posterior to the
      equator. A trained cytologist analysed all the smears. RESULTS. Specific results
      were obtained in 14 of the 17 (82%) patients studied by FNAB. Ten cases were
      neoplastic (8 malignant and 2 benign), 3 were inflammatory and 1 was a case of
      histiocytosis X. In 3/17 cases the results were non-specific. These were treated
      as pseudotumours and responded well to systemic steroids. In 7 cases the clinical
      and radiological diagnosis was confirmed by FNAB. Non-invasive investigations
      like USG, CT and MRI, however, failed to provide accurate diagnosis in the other
      7 (41%) cases. In these patients, FNAB yielded a pathological diagnosis
      (histiocytosis X, cryptococcosis, non Hodgkin's lymphoma, adenocarcinoma,
      pleomorphic adenoma, Schwannoma and cysticercosis), helping us to modify
      treatment with an excellent response. No significant complications were
      encountered following the aspiration biopsies. CONCLUSION. FNAB proved to be a
      reliable method for distinguishing between malignant and non-malignant lesions.
      It was found to be rapid, accurate, cost-effective, safe and a valuable addition
      to ultrasound, CT scan and MRI in the diagnosis of orbital lesions. This tool may
      help in avoiding a traumatic surgical intervention. 

PMID- 12045932
TI  - Orbital meningioma, the Utrecht experience.
AB  - AIMS. 1) To evaluate epidemiological data (age, gender, initial complaints, and
      ophthalmic findings) of a patient cohort with a primary or secondary orbital
      meningioma. 2) To evaluate the clinical course of these patients. 3) To evaluate
      the outcome of treatment. PATIENTS AND METHODS. All consecutive patients with a
      presumed meningioma with orbital involvement seen at the Academic Medical Center,
      Utrecht, in the period 1/1/1992-31/12/1999 were evaluated retrospectively.
      RESULTS. Sixty-three patients with either an optic nerve sheath (n = 16) or a
      sphenoid ridge or tuberculum sellae meningioma (n = 47) were seen (mean age: 41.9
      and 47.6 years, respectively); 20 of these had been treated neurosurgically
      previously. Fifty-three were females. The most frequent initial symptoms in both
      groups were proptosis and visual complaints. Thirty-three patients were followed
      without treatment, eight of them showing a lingering worsening of vision and a
      slow increase of tumor mass. Thirty patients were operated for different reasons
      (to confirm the diagnosis, or because of decreasing vision, disfiguring
      proptosis, threatening of the optic chiasm, or severe retrobulbar pain). Life
      threatening problems did not occur, cranial nerve damage being the most frequent
      complication. Macroscopic radical tumor resection was only obtained in about 50%
      of the operated patients, but immediate (partial) relief of subjective complaints
      was obtained in up to 90%. A recurrence with clinical symptoms was seen in two
      patients within the relatively short follow-up period. CONCLUSIONS. Proptosis
      and, secondly, vision complaints are the most frequent symptoms in patients with
      either a primary or a secondary orbital meningioma. Their clinical course is
      extremely variable. Loss of vision is frequently seen in both groups.
      Orbitoneurosurgical meningioma resection has a high immediate success rate.
      Damage to cranial nerves is the most frequent complication of meningioma
      resection. 

PMID- 12045933
TI  - Dynamic 3D computer-assisted reconstruction of a metallic retrobulbar foreign
      body for diagnostic and surgical purposes. [Case report of orbital injury with
      ethmoid bone involvement].
AB  - The main goal of our dynamic 3D computer-assisted reconstruction of a metallic
      retrobulbar foreign body following orbital injury with ethmoid bone involvement
      was to use 3D-information obtained from standard computed tomography (CT) data to
      explore and evaluate the nasal cavity, ethmoidal sinuses, retrobulbar region, and
      the foreign body itself by simulated dynamic computed visualization of the human
      head. A foreign body, 10 x 30 mm in size, partially protruded into the posterior
      ethmoidal cells and partially into the orbit, causing dislocation and compression
      of the medial rectus muscle and inferior rectus muscle. The other muscles and the
      optic nerve were intact. Various steps were taken to further the ultimate
      diagnosis and surgery. Thin CT sections of the nasal cavity, orbit and paranasal
      sinuses were made on a conventional CT device at a regional medical center, CT
      scans were transmitted via a computer network to different locations, and special
      views very similar to those seen on standard endoscopy were created. Special
      software for 3D modeling, specially designed and modified for 3D C-FESS purposes,
      was used, as well as a 3D-digitizer connected to the computer and multimedia
      navigation through the computer during 3D C-FESS. Our approach achieves the
      visualization of very delicate anatomical structures within the orbit in
      unconventional (non-standard) sections and angles of viewing, which cannot be
      obtained by standard endoscopy or 2D CT scanning. Finally, virtual endoscopy (VE)
      or a 'computed journey' through the anatomical spaces of the paranasal sinuses
      and orbit substantially improves the 3D C-FESS procedure by simulating the
      surgical procedure prior to real surgery. 

PMID- 12045934
TI  - Orbital amputation neuroma causing failure of prosthesis wear.
AB  - PURPOSE. To describe an orbital amputation neuroma that developed following
      enucleation and led to the patient 's inability to wear an oc- ular prosthesis.
      METHODS. This is a retrospective case report in a private practice setting. An
      elderly woman underwent enucleation of the right eye,and subsequently developed
      orbital pain and inflammation. Systemic and local steroids proved of no benefit,
      and the socket became increasingly painful,contracted and frozen. She was unable
      to wear her prosthesis. An orbital mass was noted,and subsequently biopsied.
      RESULTS. The biopsy specimen demonstrated orbital amputation neuroma. Her pain
      was relieved. CONCLUSION. Orbital amputation neuroma should be a diagnostic con-
      sideration when a patient develops a painful orbital mass following enucleation. 

PMID- 12045935
TI  - Mesenchymal chondrosarcoma of the orbit: a clinicopathological study.
AB  - Extraskeletal mesenchymal chondrosarcoma of the orbit is a rare tumour and
      generally presents in young females. We report the clinical presentation and
      histopathological features of a case of orbital mesenchymal chondrosarcoma in a
      middle-aged man. The prognosis of this tumour is poor and though rare it should
      be kept in the differential diagnosis of orbital masses. 

PMID- 12045936
TI  - Detection of Mycobacterium tuberculosis by polymerase chain reaction in a case of
      orbital tuberculosis.
AB  - Orbital tuberculosis is quite uncommon. We report a case of orbital tuberculosis
      in a 3-year-old child from Bangladesh who presented with swelling and discharging
      sinus in the lower part of the orbit. Histopathology revealed a granulomatous
      inflammation with caseation necrosis. Polymerase chain reaction (PCR) showed
      amplification of the Mycobacterium tuberculosis genome. The patient responded to
      a course of antituberculous treatment. Mycobacterium tuberculosis should be
      considered in the differential diagnosis of inflammatory orbital disease in the
      Indian subcontinent where tuberculosis is prevalent. 

PMID- 12045937
TI  - Recurrent orbital myositis and Crohn's disease.
AB  - Diagnosis of orbital pseudotumor remains rare in Crohn's disease; to the best of
      our knowledge, only six cases have been reported. In these cases, the diagnosis
      of Crohn's disease was made before or pending that of the orbital pseudotumor. In
      the present paper, we present and discuss a new case with a concomitant evolution
      between these two diagnoses. In our case, the diagnosis of orbital pseudotumor
      was made two years before that of Crohn's disease. Orbital biopsy showed a
      polyclonal monomorphous lymphoid infiltration and supported the hypothesis that
      orbital inflammation in Crohn's disease is indirect and is probably due to immune
      mediated disorders. 

PMID- 12045938
TI  - Reinjection of autologous fat in moderately deep upper lid sulci of anophthalmic
      sockets.
AB  - The purpose of this paper is to present the author 's experience with the
      transplantation of autologous adipose tissue into the moderately deep upper lid
      sulci of anophthalmic sockets. Coleman's lipostructuring technique may help
      oculoplastic surgeons with patients requiring cosmetic improvements; however,
      reinjection of autologous fat can be done only if it is known that the intra
      orbital implant is of a suitable size and that there are no orbital volume
      deficits. In this study, the patient's own adipose tissue is harvested by the
      technique of liposuction by syringe, without trauma, and then refined and
      reinjected in an intricate layering of fat tissue via microcannulae. The author
      describes the technique and results after one year of follow-up. 

PMID- 12045939
TI  - Magnetic resonance imaging of the orbit: Basic principles and anatomy.
AB  - This review article gives a basic introduction to the technical principles of
      magnetic resonance imaging for ophthalmologists and orbital surgeons and
      describes the anatomical structures that can be identified on high-resolution
      magnetic resonance images of the orbit. The meaning of general imaging
      parameters, specific weighting of the images, and the use of contrast agents, fat
      suppression techniques and surface coils is explained. Possible artifacts are
      also described. The advantages and disadvantages of MRI in comparison with
      computed tomography (CT) are discussed in order to give recommendations for the
      use of the appropriate imaging modality in patients with orbital disorders. Apart
      from delineating the course of the extraocular muscles, high-resolution MRI is
      able to depict not only all important blood vessels and cranial nerves of the
      orbit but also major septa of the orbital connective tissue system. Clinical
      applications are also mentioned to show that high-resolution MRI may contribute
      to a specific diagnosis in orbital disease. 

PMID- 12045940
TI  - Wegener's granulomatosis: The ocular manifestations revisited.
AB  - AIM. To investigate whether the extent of ocular morbidity had de-creased as a
      result of improved diagnosis, awareness and treatment of Wegener 's
      granulomatosis (WG). MATERIALS AND METHODS. A retrospective study of all patients
      with ophthalmic involvement due to WG over an 8-year period. RESULTS. Forty-nine
      patients were diagnosed to have WG. Of these, 28 had ocular involvement: 21
      patients had focal ocular involvement (conjunctivitis, episcleritis, scleritis,
      keratitis, iritis, retinitis)and 7 had orbital involvement. Permanent visual loss
      occurred in three patients with orbital involvement, but in no patients with
      focal ocular disease. Up to 90% of patients had systemic involvement. Three
      deaths oc- curred among those with ocular involvement. CONCLUSIONS. Patients with
      WG have a much improved visual prog- nosis as a result of early diagnosis and
      intervention with systemic im- munosuppression. A combination of assays for ANCA
      and tissue biop-sies were needed to establish the diagnosis of WG. Treatment with
      immunosuppressive agents (usually prednisolone and cyclophospha- mide)led to a
      good response in the majority of cases. 

PMID- 12045941
TI  - Carcinoid metastasis to extraocular muscles: case reports and review of the
      literature.
AB  - Carcinoid tumors are slow growing, low-grade malignant neoplasms that are
      believed to originate from neuroendocrine cells, usually in the gastrointestinal
      mucosa. Metastasis of carcinoid tumor to the orbit is a rare occurrence. When
      metastasis does occur, the choroid is the most common ocular structure involved.
      We report two cases of unique involvement of extraocular muscles. 

PMID- 12045942
TI  - Evaluation of lacrimal system outflow in the newborn by dye tests.
AB  - PURPOSE: The aim of this study was to evaluate the outflow from the lacrimal
      excretory system (LES) at birth. METHOD: Two-hundred LES were evaluated by the
      Milder Test (DDT) and the modified Jones I Test (JIT) in 100 newborns (NBs) from
      31 (T1) until 42 (T3) weeks of gestational age. The occurrence of obstruction was
      related to sex, weight at birth, presence of ocular discharge and the degree of
      maturity. RESULTS: Both tests were in agreement and showed LES obstruction in
      61.5% (DDT) and 78.5% (JIT), respectively, while the LES outflow increased with
      increasing maturity. CONCLUSION: Evaluation of LES outflow at birth reveals
      obstruction rates that are much higher than those clinically observed in children
      with complaints of epiphora. 

PMID- 12045943
TI  - Orbital fractures due to domestic violence: an epidemiologic study.
AB  - Domestic violence is an important cause of orbital fractures in women. Physicians
      who treat patients with orbital fractures may not suspect this mechanism of
      injury. The purpose of this study was to assess the association between domestic
      violence and orbital fractures. A medical center-based case-control study with
      matching on age and site of admission was done. Medical center databases were
      searched using ICD-9 codes to identify all cases of orbital fractures encountered
      during a three-year period. Medical records of female patients age 13 and older
      were reviewed along with those of age, gender and site of admission matched
      controls. A stratified exact test was employed to test the association between
      domestic violence and orbital fracture. Among 41 adult female cases with orbital
      fractures treated at our medical center, three (7.3%) reported domestic violence
      compared to zero among the matched controls (p = 0.037). We believe that domestic
      violence may be under-reported in both orbital fracture cases and controls. This
      may result in an underestimate of the orbital fracture versus domestic violence
      association. Domestic violence is a serious women's health and societal problem.
      Domestic violence may have a variety of presentations, including illnesses and
      injuries. Orbital fracture is an identifiable manifestation of domestic violence.
      Domestic violence is more likely to be detected in adult female hospital patients
      with orbital fracture than in matched controls with any other diagnosis.
      Physicians who treat patients with orbital fractures should be familiar with this
      mechanism of injury. 

PMID- 12045944
TI  - Orbital fibrous histiocytomas.
AB  - Orbital fibrous histiocytomas can be difficult to diagnose and manage. These
      tumors, especially those with intermediate histologic features, often recur.
      Historically, non-invasive tests to differentiate scars from recurrent disease
      have a high error rate. We present a case of recurrent orbital fibrous
      histiocytoma in which the diagnosis was established with poitron emission
      tomography (PET) scans. This technique may be helpful in difficult cases to
      differentiate scars from a recurrent mesenchymal tumor. 

PMID- 12045945
TI  - Dermatofibroma of the eyelid: a case report.
AB  - A 5-year-old girl presented with a large swelling measuring 50 x 35 mm in the
      left upper lid. The mass was firm to hard in consistency. Fine-needle aspiration
      showed a few spindle-shaped cells arranged in clusters. The mass was excised in
      toto and the histopathological examination revealed dermatofibroma, which is an
      extremely rare condition affecting the eyelid. 

PMID- 12045946
TI  - Traumatic globe luxation with optic nerve transection.
AB  - Luxation of the globe is a rare event that results from severe trauma to the
      orbit, often causing orbital rim and wall fractures. Though associated globe
      rupture often necessitates enucleation, repositioning of the globe can be
      attempted in these cases if the globe is intact. We report a case of globe
      luxation and optic nerve transection with its surgical management. A 17-year-old
      male presented with anterior luxation of the right globe and optic nerve
      transection following blunt trauma to the orbit. Computerized tomography revealed
      an anteriorly subluxated globe with complete transection of the optic nerve and
      multiple fractures of the orbital walls. The orbit was explored and the globe
      repositioned in the orbit with reattachment of the muscles. Postoperatively, the
      globe was in normal position with moderate motility and excellent overall
      cosmesis. Though the visual prognosis in these cases is usually extremely poor
      and depends on the extent and duration of injury, preservation of the globe not
      only helps the patient recover psychologically from the trauma but also allows
      better cosmesis. 

PMID- 12045947
TI  - Primary neuroendocrine carcinoma ("Merkel cell tumor") of the eyelid: a report of
      two cases.
AB  - BACKGROUND. Merkel cell tumor is an uncommon, aggressive neoplasm of the skin,
      now regarded as a neuroendocrine carcinoma. Eyelids are among the sites where it
      can develop, often mimicking a benign process. The purpose of this report is to
      describe two new cases and to discuss briefly the problems of diagnosis and
      treatment. METHODS. Two patients with Merkel cell tumor of the eyelids are
      described. In both cases, the original clinical diagnosis was chalazion.
      Progressive growth of the lesion identified it as a tumor some 2-7 months after
      it was first noticed. The patients were treated by surgical excision of the tumor
      tissue, and only one by a course of local radiotherapy. The visual acuity was
      measured with Snellen fractions. The dose of local radiotherapy is given in cGy.
      RESULTS. Histopathological and immunohistochemical studies identified the lesion
      as a neuroendocrine carcinoma, consistent with Merkel cell tumor. The natural
      history was marked by aggressive behavior in one case, and by a delayed
      recurrence in the other, requiring different therapeutic approaches. CONCLUSION.
      Merkel cell carcinoma of the eyelid is a tumor that ophthalmogists should be
      aware of, as early diagnosis is a prerequisite for successful treatment. Rapid
      recurrence of any chalazion in a middle-aged or elderly patient should therefore
      prompt its histological examination to exclude the possibility of a malignant
      tumor. 

PMID- 12045948
TI  - Role of ultrasound and CT-scan in diagnosis of hydatid cyst of the orbit.
AB  - Hydatid cyst of the orbit is a rare cause of proptosis, even in endemic countries
      like India. We report two histopathologically proven cases with ultrasonographic
      and computerized tomographic correlations. Both patients had marked dimness of
      vision and disc edema. One of them did not regain vision following cyst removal
      because of optic atrophy. The two cases indicate that hydatid cyst should be
      retained as a differential diagnosis of unilateral proptosis with disc edema. A
      combined ultrasound and CT-scan should be done to establish the diagnosis. An
      attempt should also be made at complete surgical removal of the cyst. 

PMID- 12045949
TI  - Incidence of lagophthalmos after aponeurotic ptosis repair.
AB  - This study was designed to determine the incidence of lagophthalmos following
      aponeurotic ptosis repair, and to establish any predictive factors for its
      development. Data from a prospective, interventional, non-comparative case series
      was reviewed. Of these 164 eyelids with acquired involutional ptosis, 134 eyelids
      of 75 patients had both preoperative and postoperative photographs of the eyelids
      in the primary and gently closed positions, and were therefore analyzed for this
      study. Lagophthalmos was present in 23/38 (60%) of eyelids on the first
      postoperative day; in 27/81 (33%) one week after surgery; and persisted in 12/134
      (9%) eyelids and 8/75 (11%) patients six to twenty weeks after surgery (mean 11
      weeks). The lagophthalmos of these twelve eyelids ranged from 0.5 to 1.5 mm with
      a mean of 0.6 mm. Both the pre-existing lower scleral show and the final height
      of the eyelid following surgery were significant predictors of postoperative
      lagophthalmos. Neither eyelid excursion nor the degree of change in eyelid height
      from pre- to post-surgery was significantly associated with eyelid closure. 

PMID- 12045950
TI  - Possibilities and limits of minimal invasive lacrimal surgery.
AB  - Endoscopy of the lacrimal drainage system with miniaturized endoscopes has been
      possible since 1990 and permits the direct evaluation of the lacrimal drainage
      system. Additionally, attached instruments permit recanalization in cases of
      stenosis of the lacrimal drainage system. Both an Erbium-Yag Laser and a
      miniaturized drill are available, with which a stenosis of the lacrimal drainage
      system can be opened under endoscopic control. Favorable findings for endoscopic
      recanalization are stenoses in the area of the canaliculi or the lacrimal sac,
      for which the success rate of recanalization is approximately 75%. Unfavorable
      prognostic factors are submucous scar formations due to a dacryocystitis in the
      patient's history. Endoscopic findings have also improved the understanding of
      diseases of the lacrimal drainage system. Punctal stenoses causing epiphora often
      show intact mucous membranes before and behind the stenosis and it is possible to
      cure these patients without extensive surgical procedures. Micro-surgical
      procedures and dacryocystorhinostomy complete the spectrum of the endoscopic
      surgical possibilities in the lacrimal drainage system. 

PMID- 12045951
TI  - The correlation of clinical lacrimal bone density and thickness, established at
      the time of DCR surgery, with systemic bone mineral densitometry testing.
AB  - BACKGROUND. Due to a growing concern with regard to the relationship between
      osteoporosis and fractures, we wished to examine the correlation of systemic bone
      density with lacrimal bone characteristics (thickness and density), as measured
      at the time of dacryocystorhinostomy (DCR). Significant correlation would suggest
      that oculoplastic surgeons may screen for osteoporosis during DCR. METHODS. A
      prospective study of the bone mineral density in patients (n=32) undergoing DCR
      was conducted. During DCR, the lacrimal bone thickness and density were estimated
      clinically. Postoperatively, the systemic bone density was measured by dual
      energy x-ray absorptiometry (DEXA) scanning. The data were analyzed using
      Student's t-test, Pearson correlation and Pearson chi-square methods. RESULTS.
      Analyzed in a bivariate arrangement, significant correlation (p<0.05) was
      detected between the systemic bone density (as measured at two sites, the femoral
      head and lumbar spine) and the lacrimal bone characteristics (thickness and
      density). Therefore, the lower the lacrimal bone thickness or density, the lower
      the systemic bone density. INTERPRETATION. With the finding of significant
      correlation between lacrimal bone thickness and density and systemic bone
      density, oculoplastic surgeons can screen for osteoporosis during DCR. If low
      density thin bone is encountered during DCR, the patient's general practitioner
      should be alerted. 

PMID- 12045952
TI  - The intranasal ostium after external dacryocystorhinostomy and the internal
      opening of the lacrimal canaliculi.
AB  - The purpose of this paper was to evaluate the appearance and location of the
      healed intranasal ostium and the internal aperture of the common canaliculus
      after uncomplicated external dacryocystorhinostomy (DCR). In 21 patients who
      underwent uncomplicated external DCR, the distances between the lacrimal puncta
      and the internal aperture of the common canaliculus were measured during surgery.
      The measurements were taken with a 1 mm diameter Bowman probe graded in
      millimeters. These measurements were recorded and considered the landmarks for
      the spatial localization of the internal aperture of the canaliculus. After
      surgery, under endoscopic control, the same method was used to measure the
      distance between the lacrimal puncta and the internal ostium, which was defined
      as the aperture through which it was possible to visualize the very first
      protrusion of the probe into the nose. The intra- and post-operative measurements
      were compared. Endoscopic photos of the healed endonasal ostium were also taken.
      The photos showed that when DCR procedures were not complicated by scarring or
      mucosal adhesions, the lacrimal sac became a depression perfectly integrated
      within the nasal mucosa. The scar at the site of junction between the nasal and
      the lacrimal sac mucosa appeared as a large-diameter pearl-like colored frame
      that surrounded the depression. In the context of the depression a small
      aperture, which presented a diameter of around 2 mm, could be easily visualized.
      The spatial location of this aperture corresponded to the internal aperture of
      the common canaliculus (p < 0.05). 

PMID- 12045953
TI  - Cytogenetic analysis of rare orbital tumors: further evidence for diagnostic
      implication.
AB  - INTRODUCTION. The pathologic diagnosis, and hence the management, of rare tumors
      of the orbit can represent a challenge. An increasing number of tumors have been
      shown to display specific chromosomal abnormalities detectable by cytogenetic
      analysis. MATERIALS AND METHODS. Two examples of rare primary orbital tumors are
      presented in which the correct pathologic diagnosis was either established or
      confirmed by cytogenetic analysis. Small pieces of the tumor were obtained at the
      time of biopsy and placed immediately, in a sterile fashion, in fresh culture
      medium. The cells were Giemsa stained and processed for chromosome analysis.
      RESULTS. In the first case, a 12-year-old boy was diagnosed with a sino-orbital
      mass after sustaining minor trauma. On biopsy, the pathologic examination was at
      first consistent with a Burkitt-like lymphoma, until cytogenetic analysis showed
      a t(8;21)(q22;q22) translocation, specific for granulocytic sarcoma, which
      corresponds to the localized solid form of acute myeloblastic leukemia.
      Consequently, proper chemotherapy was re-oriented and remission was achieved. In
      the second case, a 2-year-old boy presented with a well-vascularized orbital
      tumor. The histopathologic diagnosis of alveolar soft-part sarcoma of the orbit
      was confirmed by the finding of a specific t(X;17)(p11;q25) translocation. After
      two unsuccessful courses of chemotherapy, wide excision surgery with primary
      reconstruction brought remission. CONCLUSIONS. Cytogenetic analysis should be
      considered in the diagnosis of any orbital tumor which is suspected of
      malignancy. 

PMID- 12045954
TI  - Chronic inflammation in dermoid cysts: a clinicopathologic study of 115 patients.
AB  - PURPOSE. To analyze the frequency, pattern, and extent of chronic inflammation in
      orbital and periorbital dermoid cysts and to correlate these findings with
      clinical data. PATIENTS AND METHODS. We reviewed the clinical and histopathologic
      data of 115 consecutive patients with histopathologically confirmed orbital or
      periorbital dermoid cysts between 1980 and 1998. RESULTS. Sixty-one patients were
      male and 54 female. Their mean age at the time of surgery was 13 years. The
      lesion was located superotemporally in 71% of the patients. Patients presented
      most commonly with a palpable mass without clinical signs of inflammation. The
      mean cyst volume was 1276 mm(3) (range: 72 to 9900 mm(3)). Histopathologically,
      50 lesions (43%) showed chronic granulomatous inflammation of the cyst wall. In
      16% of them, the inflammatory response completely replaced the epidermal elements
      and the normal architecture of the cyst wall. Nine lesions showed spread of
      granulomatous cell infiltration to the surrounding tissue. Granulomatous
      inflammation was detected more frequently (p<0.001, chi-square test) with
      increasing age in patients younger than 30 years, being found in 25% of the
      patients aged 5 years or younger and in 80% of the patients between 16 and 30
      years of age. It was also more common (p<0.001, chi-square test) in cysts larger
      than 1000 mm(3). CONCLUSION. The frequency of chronic granulomatous inflammation
      of dermoid cysts and its correlation with patient's age and cyst volume suggest
      that patients should be operated before the age of five years and that large
      dermoid cysts (>1000 mm(3)) should be removed early. 

PMID- 12045955
TI  - Balanced orbital decompression in Graves' orbitopathy: Upper eyelid crease
      incision for extended lateral wall decompression.
AB  - INTRODUCTION. This study reports on the results and complications detected in
      patients with Graves' orbitopathy who underwent balanced medial and lateral wall
      orbital decompression through concealed incisions. MATERIALS AND METHODS. The
      medial and lateral orbital walls of nine consecutive patients (14 eyes) were
      removed. A transnasal endoscopic spheno-ethmoidectomy was performed for the
      medial wall decompression. A lateral wall decompression was performed via an
      upper eyelid crease incision which was extended laterally in a relaxed skin
      tension line. The lateral aspect of the orbit was sculpted with a high-speed
      surgical drill from the inferior orbital fissure inferiorly and frontal bone of
      the lacrimal fossa superiorly to the orbital apex posteriorly, including the
      thick bone of the greater wing of the sphenoid. RESULTS. The decompression was
      performed for cosmetic purposes in seven patients (10 orbits) and for exposure
      keratopathy and restrictive myopathy in the remaining two patients (4 orbits).
      The average follow-up period was 13.6 months. The mean reduction of proptosis was
      4.8 mm. The preoperative diplopia in two cases demonstrating restrictive myopathy
      worsened during the postoperative period. New onset diplopia was not detected in
      seven cases operated on for cosmetic purposes. All patients were satisfied with
      their eye status, visual rehabilitation and cosmetic appearance. CONCLUSIONS. The
      transnasal endoscopic approach for medial wall and extended lateral wall
      decompression with hidden eyelid crease incision provides a favorable cosmetic
      and physiologic outcome with proper retroplacement of the globe. 

PMID- 12045956
TI  - Fronto-orbital fibrous dysplasia.
AB  - Fibrous dysplasia, which is characterized by a disorganized mixture of fibrous
      and osseous elements in the affected bones, is a non-neoplastic developmental
      anomaly caused by an activating mutation. Despite an identical histological
      pattern, the clinical behavior varies according to the site of involvement.
      Fronto-orbital lesions behave more aggressively and generally continue to grow
      during adulthood. During the last 20 years, 32 cases of fronto-orbital fibrous
      dysplasia have been treated and the results of treatment have been assessed. The
      indications for surgery were mainly visual deterioration due to optic nerve
      compression, globe malposition and widespread disease causing gross facial
      deformity. The treatment of these patients consisted of radical resection of the
      fibro-osseous tissue, decompression of the optic nerve canal and reconstruction
      of the resected fronto-orbital areas with either noninvolved bone grafts or with
      dysplastic bone which was contoured down or, in one case, heated in the
      sterilizer. Recently, Pamidronate, a bone resorption inhibitor, has been added to
      the treatment protocol. During follow-up there have been two recurrences, repeat
      optic nerve decompression has not been required and overall the esthetic results
      are satisfactory. Fronto-orbital fibrous dysplasia can have a devastating outcome
      with high recurrence rates and blindness, especially following incomplete
      resection. A radical and extensive approach to treatment is recommended; this
      seems to be the best choice as witnessed by the good results achieved in this
      series. 

PMID- 12045957
TI  - Oculomotor palsy with cyclic spasms: a case report.
AB  - Oculomotor palsy with cyclic spasms is a rare, non-progressive disorder in which
      the muscles innervated by the third cranial nerve undergo alternating rhythmic
      spasm and paralysis. An 18-year-old male was referred with left upper eyelid
      ptosis present since birth. On examination we noted cyclic movements of the left
      eyelid and pupil. The cycle consisted of periods of ptosis and mydriasis
      alternating with eyelid retraction with miosis. The interpalpebral fissure
      measured 2 mm in the paralytic phase and 11 mm in the spastic phase. The pupil
      diameter varied from 3 mm to 6 mm. Six cycles were observed in 5 minutes. The
      patient had no voluntary control over his left eyelid, nor over the other muscles
      innervated by the third nerve. The affected eye was deeply amblyopic and
      exotropic. Systemic evaluation and cranial MRI gave normal results. A therapeutic
      trial with oral baclofen (30 mg/day), a central muscle relaxant drug, was
      ineffective in suppressing the cyclic movements. 

PMID- 12045958
TI  - Combined congenital dacryocoele and anterior orbital hydrencephalocoele.
AB  - The differential diagnosis of a medial canthal cystic mass in the new-born child
      includes dacryocoele, dermoid and, much more rarely, encephalocoele. We present a
      child with coexistent bilateral dacryocoeles and bifrontal anterior orbital
      hydrencephalocoeles. 

PMID- 12045959
TI  - Malignant apocrine sweat gland carcinoma of the caruncle.
AB  - A 34-year-old male presented with a mass in the medial aspect of the orbit.
      Histological examination demonstrated a malignant apocrine sweat gland carcinoma,
      which we consider to be most likely derived from the caruncle. We describe the
      clinical, radiological and histological features, with management options and a
      review of the relevant literature regarding sweat gland carcinomas. 

PMID- 12045960
TI  - Conjunctival cyst and conjunctival dermoid of the orbit.
AB  - BACKGROUND. Conjunctival dermoids and conjunctival cysts of the orbit were first
      reported by Jakobiec et al. in 1978. Communications regarding this type of cysts
      have been sporadic. PATIENTS AND METHODS. We describe the clinical and
      histopathologic findings in two patients with histopathologically confirmed
      conjunctival dermoid and conjunctival cyst of the orbit. A review of the
      literature was also carried out. RESULTS. A 27-year-old female presented with a
      slowly growing tumor in her left orbit inferomedially. Histopathologically, the
      tumor was a conjunctival cyst. A 20-year-old male was seen with a painless,
      slowly-growing mass in his right orbit nasally. The histopathologic study
      disclosed a conjunctival dermoid. Echography was useful in both cases in
      demonstrating the cystic structure of the tumors. Conjunctival dermoids and cysts
      are usually noticed in adulthood, are located nasally or superonasally, lack an
      associated osseous defect and are lined by a non-keratinizing epithelium with
      goblet cells. CONCLUSION. Conjunctival dermoids and cysts of the orbit display
      clinical, radiologic and histopathologic features that differentiate them from
      the more common dermoid cysts. Emphasis must be given to these distinctive
      features, since these lesions have probably been largely misdiagnosed. 

PMID- 12045961
TI  - Primary orbital melanoma associated with oculodermal melanocytosis.
AB  - A 29-year-old, otherwise healthy man presented with an approximately 5-months'
      history of left-sided exophthalmos. The patient had a bluish-black pigmentation
      on his left upper lid, and black pigmentation on the left conjunctiva and sclera,
      since birth. CT examination revealed a retrobulbar tumor in the left orbit, and
      the left medial rectus muscle was wider than the right one. The left orbital
      cavity and the superior orbital fissure were enlarged. All of the examinations
      were negative in respect of another primary tumor outside the orbit or of tumor
      dissemination. At surgery, a pigmented tumor was found and removed. The orbital
      tissues were darkly pigmented. Histological examination of the excised tumor
      showed it to be an encapsulated, circumscribed mass. The tumor was built up of
      fusiform and spindle-shaped cells containing black pigmentation, with very few
      mitoses and without necrosis. There has been no recurrence or metastasis in 3
      years of follow-up. The consequences of the tumorous transformation of
      oculodermal melanocytosis as reflected in the published literature and the
      special clinical and histopathological characteristics of our case are discussed.

PMID- 12045962
TI  - Adenoid cystic carcinoma of the superonasal conjunctival fornix.
AB  - The case of a 32-year-old female with a mass in the superonasal conjunctival
      fornix is described. Histological examination revealed an adenoid cystic
      carcinoma, which we consider to be most likely derived from an accessory lacrimal
      gland. The clinical presentation, histological features, management and follow-up
      are described. A literature review of orbital adenoid cystic carcinoma arising
      outside the main lacrimal gland is presented. 

PMID- 12045963
TI  - Surgical treatment of cicatricial ectropion in lamellar ichthyosis.
AB  - BACKGROUND. Lamellar ichthyosis is a skin disorder that is frequently associated
      with cicatricial ectropion and lagophthalmos. The authors present the surgical
      management of cicatricial ectropion in a case with lamellar ichthyosis. PATIENT
      AND METHODS. A 2-year-old male presented with bilateral cicatricial ectropion of
      the upper and lower eyelids. He had lagophthalmos and corneal punctuate staining.
      His skin was totally involved with the disease process except his prepuce. The
      patient was circumcised, and after the correction of horizontal eyelid laxity,
      the penile skin graft was sutured into the defects in all four eyelids. RESULTS.
      18 months following surgery the patient had no lagophthalmos or corneal exposure,
      but had slight ectropion at the temporal side of the left lower eyelid. He had no
      complications from the circumcision. CONCLUSION. Prepuce is an alternative donor
      tissue in male patients with no other available donor site. To our knowledge,
      this is the second report of cicatricial ectropion corrected with a penile skin
      graft. 

PMID- 12045964
TI  - Orbital cellulitis with gas.
AB  - Orbital cellulitis due to presumed gas-producing organisms has been associated
      with poor visual prognosis. We report successful visual recovery in a 14-year-old
      boy with orbital cellulitis and gas in the orbit on CT scan. The patient was
      treated with intravenous antibiotics and prompt orbital decompression. Pus from
      the sinus aspirate and orbital drain grew H. influenzae and Gram-negative
      bacilli. Repeat orbital surgery with drainage of residual abscess was performed
      and the patient made a complete recovery. 

PMID- 12045965
TI  - Curvularia dacryocystitis: report of two cases.
AB  - Two cases of ocular mycosis caused by the genus Curvularia are reported. In these
      cases, the infection was localised to the lacrimal sac only and presented in the
      form of acute to chronic dacryocystitis. Interestingly, neither of the hosts was
      immunocompromised. The authors have not been able to find a similar presentation
      of ocular mycosis caused by Curvularia localised to the lacrimal sac in the
      literature. The relevant literature pertaining to ocular involvement with this
      fungus is discussed. The authors recommend the use of oral fluconazole for a
      minimum of two weeks for the treatment of such infections as a good therapeutic
      response was obtained with this agent in both their cases. 

PMID- 12045966
TI  - Metastatic malignant teratoid medulloepithelioma - a case report and review of
      the literature.
AB  - Medulloepitheliomas are rare congenital tumours arising from the epithelium
      lining the medullary tube. They are usually detected in the first decade of life.
      They may be teratoid or non-teratoid. Regional and distant metastases are rare.
      Extraocular extension of disease appears to be the most important prognostic
      feature. Surgical resection is the usual mode of treatment. The role of other
      adjuvant modalities is as yet unclear. 

PMID- 12045967
TI  - "Goodbye" and "Hello"

PMID- 12045968
TI  - Use of mitomycin C and 5-fluorouracil in external dacryocystorhinostomy.
AB  - PURPOSE. To evaluate the effects of antiproliferative agents on the fibrous
      tissue responsible for the failure of external dacryocystorhinostomy at the site
      of surgical rhinostomy. METHODS. The study group consisted of 60 cases. Patients
      with primary acquired idiopathic nasolacrimal duct obstruction were divided into
      three groups according to the agent used. Each group consisted of 20 patients.
      Mitomycin C was applied to the first group (0.5 mg/ml to 10, 1 mg/ml to 10 cases)
      and 5-flourouracil to the second group (2.5 mg/ml to 10, 5 mg/ml to 10 cases).
      The third group consisted of 20 control cases. The mean follow-up period was 15.3
      +/- 2.60 (12-18) months. The tissues obtained during the revision of the cases
      with failure were evaluated by light and electron microscopic examination.
      RESULTS. External dacryocystorhinostomy failed in four cases. Of these, one was
      in the first group (0.5 mg/ml mitomycin C), one in the second group (2.5 mg/ml 5
      flourouracil), and two were in the control group. Light microscopic examination
      of the tissues revealed an increase in fibroblastic activity in the control group
      whereas hypo- and acellular areas were found to be dominant in the groups given
      antifibroblastic agents. The control group revealed more active fibroblasts with
      cytoplasms containing numerous organelles in electron microscopic examination.
      Electron microscopic examination of the cases given antifibroblastic agents
      revealed fibroblastic cells with nuclear fragmentation, necrosis or pyknosis,
      while some others had scanty cytoplasms poor in organelles. CONCLUSION. We can
      conclude that intraoperative antiproliferative agents improve the success rate of
      external dacryocystorhinostomy. 

PMID- 12045969
TI  - Evaluation of findings in Crouzon's syndrome.
AB  - PURPOSE. The purpose of this study was to investigate the ocular, facial and
      radiological signs of Crouzon's syndrome in a group of older patients who had not
      undergone previous craniofacial surgery. METHODS. Six cases of Crouzon's
      syndrome, four of whom belonged to a three-generation family, were examined
      systemically, ophthalmologically and roentgenographically; five of these cases
      were additionally evaluated with computed tomography and compared with Apert
      syndrome. RESULTS. On radiologic evaluation, all cases had synostosis of all
      cranial sutures and fontanelles and brachycephalic skulls, crowding of the upper
      teeth due to maxillary hypoplasia, and serious nasal septum deviation. Bilateral
      ethmoidal, maxillary and sphenoidal chronic sinusitis was found in 50% of cases.
      Three patients had hypertelorism and two others had a tendency toward
      hypertelorism. The typical facial appearance with shallow orbits, globe
      protrusion and exorbitism was present in all cases. Two of them had V-pattern
      exotropia while the other four were orthophoric. The single case with mental
      retardation had bilateral cataract. CONCLUSION. Crouzon's syndrome can present
      with different findings and must be evaluated multidisciplinarly. 

PMID- 12045970
TI  - Thallium-201 SPECT of orbital tumors.
AB  - Thallium-201 ((201)Tl) SPECT is utilized as a diagnostic imaging tool for a
      variety of tumors, such as lung cancer, brain tumors, etc., but there is hardly
      any literature on this type of imaging in orbital lesions. We examined 22
      patients with orbital lesions and unilateral exophthalmos to evaluate the
      usefulness of (201)Tl-SPECT in the diagnosis of orbital tumors. All 22 cases had
      a confirmed histopathological diagnosis. The patients underwent (201)Tl-SPECT
      imaging before therapy. Early images were obtained 15 minutes after the
      intravenous administration of 74 MBq (201)Tl-chloride, and delayed images were
      taken 3 hours later. The intensities of (201)Tl accumulation in the early and
      delayed images were measured. Three out of four patients with cavernous
      hemangiomas, one of two with neurinomas, all three with pleomorphic adenomas, one
      with lipoma, and one with dermoid cyst had negative scans, but the other 13
      patients all displayed ( 201)Tl accumulation in the area of the tumor. Four
      malignant lymphomas, two reactive lymphoid hyperplasias, one meningioma, one
      neurinoma, one adenoid cystic carcinoma and one plasmacytoma showed increased
      uptake, especially in the early phase. The most intense uptake was seen in the
      metastic renal cell carcinoma, in both early and delayed phases. We conclude that
      (201)Tl-SPECT can be useful in predicting the histopathological diagnosis of
      orbital tumors, especially by comparing the accumulation rate in the early and
      delayed phases. 

PMID- 12045971
TI  - Pulmonary carcinoid tumor presenting with simultaneous orbital and intracranial
      metastases: value of transnasal endoscopic orbital biopsy and decompression.
AB  - A 62-year-old woman presented with a 10-week history of blurred vision in the
      left eye. Examination revealed mild limitation of upgaze of the left eye and
      evidence of a left optic neuropathy. Magnetic resonance imaging revealed an
      enhancing mass in the posteromedial left orbit as well as an enhancing lesion in
      the inferior occipital lobe. The patient underwent a left orbital biopsy and
      partial decompression via a left nasal endoscopic approach, following which the
      optic neuropathy improved significantly. Histopathologic examination yielded a
      diagnosis of carcinoid tumor. Biopsy of the occipital lesion was also consistent
      with this diagnosis. The primary tumor was found in the lungs. 

PMID- 12045972
TI  - Orbital "shanking": a unique prison injury.
AB  - The purpose of this paper is to describe orbitocranial penetration due to
      "shanking", a common mode of assault in prison facilities. We report the case of
      a prisoner who presented with orbital apex syndrome 5 days after an assault. He
      died 9 days after surgical removal of the "shank" due to a presumed ruptured
      traumatic aneurysm. Physicians who evaluate prisoners must maintain a high index
      of suspicion for penetrating injuries. The entrance site is often inconspicuous
      and the history may be limited in this unique population. 

PMID- 12045973
TI  - Mycobacterium of an unknown strain causing a primary tumoral process of the
      orbital roof.
AB  - PURPOSE. To report an unidentified species of atypical Mycobacterium as the
      causative agent of a primary orbital roof infection. METHOD. Review of a case
      from the King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. RESULTS. The
      patient had a negative history for eye trauma. Computed tomography (CT) of the
      brain and right orbit confirmed the presence of soft tissue swelling and erosive
      changes in the orbital roof bone, with intact globe and external ocular muscles.
      Biopsy of the lesion showed non-caseating, granulomatous osteomyelitis. Various
      stains of the sample were negative. Since our institution could not identify the
      causative organism, a biopsy sample was sent to Bioscientia Laboratory in
      Germany; the culture grew an atypical Mycobacterium of unknown species. Their
      sensitivity study showed the organism to be resistant to pyrazinamide, isoniazide
      and streptomycin, but sensitive to rifampicin, ethambutol, and prothionamide.
      Systemic checkup and investigation ruled out any other systemic involvement.
      CONCLUSION. A new species of atypical Mycobacterium was recovered from a primary
      orbital infection. The infection responded to combined antituberculous therapy. 

PMID- 12045974
TI  - Orbital granulocytic sarcoma in a myelodysplastic syndrome.
AB  - PURPOSE. To report an elderly patient with a primary myelodysplastic syndrome
      (MDS) type refractory anemia with excess of blasts (RAEB) who developed an
      orbital granulocytic sarcoma (GS) as a harbinger of an acute myelogenous leukemia
      (AML). METHODS. A 77-year-old man was diagnosed as having a MDS type RAEB. Eight
      months later he developed a progressive painless proptosis in his left orbit. A
      computed tomography (CT) scan revealed a large irregular mass involving the
      orbit. It showed heterogeneous soft tissue density and no osseous cortical
      destruction was observed. A diagnostic lateral orbitotomy with an excisional
      biopsy were performed. RESULTS. Histopathology showed sheets of immature
      granulocytic cells. Immunohistochemical staining was positive for markers for
      myeloperoxidase, which supported the diagnosis of GS. CONCLUSIONS. Reports of a
      GS complicating the course of a MDS are few. Sites of detection of the
      extramedullary tumors (EMT) in MDS vary, although cutaneous sites predominate. An
      orbital site is a very rare localization of this tumor in adults. The case we
      report is the first one with an orbital granulocytic sarcoma in an MDS-type RAEB
      in an elderly patient. 

PMID- 12045975
TI  - Ossifying fibroma of the lateral orbital wall in an adult.
AB  - Orbital ossifying fibroma is an extremely rare condition, especially in adults.
      This rare tumor mostly develops at the medial wall of the orbit. We report a
      histopathologically confirmed ossifying fibroma involving the lateral orbital
      wall in an adult. This case suggests that orbital ossifying fibroma should be
      considered in the differential diagnosis of orbital bony lesions in adults and
      that unusual presentations may occur. 

PMID- 12045976
TI  - Merkel cell carcinoma: a distinct lesion of the eyelid.
AB  - Merkel cell carcinoma (trabecular cell carcinoma) is a rare, distinct, primitive,
      neuroendocrine malignancy of the skin, usually affecting elderly patients. It
      develops from Merkel cells and nearly one out of every 10 Merkel cell carcinomas
      occurs in the eyelids and periocular region. The tumor manifests itself
      clinically as a bulging lesion near the lid margin, painless, reddish colored
      with teleangiectatic blood vessels on the surface. Histologically, the tumor can
      mimic malignant lymphoma, undifferentiated melanoma, sebaceous carcinoma or
      cutaneous metastases of pulmonary microcytoma. Immunohistochemical studies with
      antibodies to neuron-specific enolase, cytokeratins and neurosecretory granules
      are necessary to differentiate these tumors. One third of all Merkel cell
      carcinomas result in death. In the present paper, we present data on the clinical
      features, treatment and long-term follow-up of three patients. 

PMID- 12045977
TI  - Ectopic brain presenting as orbital and conjunctival mass: A case report.
AB  - The presence of brain tissue in the orbit is a rare finding, whether it occurs
      isolated, in continuity with intracranial contents, or within a tumor. In this
      paper, the authors report a rare case of ectopic brain in the orbit, presenting
      as a conjunctival mass, in a 15-day-old female child. The clinical and
      histological features of the case are presented, together with a review of the
      literature. 

PMID- 12045978
TI  - Retrobulbar optic nerve cysticercosis with surgical removal: a case report.
AB  - A 15-year-old boy presented with diminution of vision which rapidly progressed to
      no perception of light. In the ocular fundus, a neuroretinitis-like picture was
      seen. On CT-scan & ultrasonography, an optic nerve swelling was detected with a
      shadow of scolex. Medical therapy in the form of steroids along with albendazole
      was ineffective. Surgical removal by lateral orbitotomy was done and a complete
      cyst with scolex was removed, which was confirmed histopathologically as a case
      of retrobulbar optic nerve cysticercosis. 

PMID- 12045979
TI  - Hydatid cysts of the orbit in Xinjiang: a review of 18 cases.
AB  - PURPOSE To review the prevalence of orbital hydatid cyst in Xinjiang, China.
      METHOD. In the records of our hospital and in the issues of Chinese medical
      journals between 1956 and 1994, we found 18 cases of orbital hydatid cyst,
      including 10 cases from our hospital, two cases from the ShiHeZi Medical College,
      three cases from the YiLi local clinical hospital, and three other cases from the
      HeTian, WuSu and Changji local hospitals. All cases were verified by operation.
      RESULTS. In our hospital, a review of 3736 cases of hydatid cyst between 1957 and
      1992 showed that hydatid cyst of the orbit accounted for 0.3%. Among the 18
      cases, 7 were males and 11 females; the age ranged from 3 to 55 years and 15
      cases were under 16 years of age (83%).The main symptom of orbital hydatid cyst
      was proptosis. Before the 1970s, the diagnosis depended on positive serological
      tests, X-ray examination and a history of infection of other parts of body with
      Echinococcus granulosus, with final confirmation by operation. In recent years,
      CT and ultrasonography have made possible a positional and qualitative diagnosis
      before surgery. With regard to the serological tests, the Intradermal test (ID)
      was positive in 77% of cases, while Indirect hemagglutination (IHA) and Counter
      immuno-electrophoresis (CIEP) were positive in two cases and negative in two
      cases, respectively. No recurrence was seen when two cases were examined by CT
      six years after the operation, nor in eight other cases followed by letter for
      between 8 and 11 years. CONCLUSIONS. Hydatid cyst is an endemic disease in
      Xinjiang, but orbital hydatid cyst is rarely seen. The diagnosis is relatively
      easy to make in endemic countries, based on the clinical features,
      ultrasonography, CT-scan and serology. The main treatment for orbital hydatid
      cyst is surgery. 

PMID- 12045980
TI  - What has become of our idiopathic inflammatory pseudo-tumors of the orbit?
AB  - OBJECTIVE. We looked for the development of specific systemic disease or
      malignant lymphoma in patients whose initial diagnosis was idiopathic
      inflammatory pseudo-tumor of the orbit (IOPT). PATIENTS AND METHODS. IOPT was
      diagnosed in 24 patients on the basis of imaging findings and surgical biopsies
      (70%). Nineteen of these 24 patients (10 men and 9 women, age range 19- 83 years)
      were reassessed 1-12 years after the initial diagnosis. RESULTS. The initial
      diagnosis described diffuse inflammation (33%), dacryoadenitis (20%) or myositis
      (47%). At reassessment, 4 patients had developed a specific disease: generalized
      lymphoma, Wegener's disease, necrotizing vasculitis, and Crohn's disease. All
      four were recognized within one year of the IOPT diagnosis. A biopsy was obtained
      in these four patients and was not contributive. One case of non-specific
      granulomatous proliferation was found 6 years after the initial diagnosis. One
      case of orbital meningioma occurred 10 years after radiotherapy of the orbit and
      could not be attributed to a definite cause. The other patients had a common non
      specific clinical course; recurrent inflammation required corticosteroid therapy
      in 55% and complementary external radiotherapy of the orbit in 22%. DISCUSSION
      AND CONCLUSION. Specific diseases that developed after an initial diagnosis of
      inflammatory pseudo-tumor of the orbit occurred early and appeared more often in
      diffuse forms, suggesting the need for more extensive histopathological
      diagnostic procedures. The clinical course tended to be more quiescent in
      patients who passed the critical period of the first year. 

PMID- 12045981
TI  - The value of nasal endoscopy after dacryocystorhinostomy.
AB  - PURPOSE To determine the value of office nasal endoscopy after
      dacryocystorhinostomy (DCR). METHODS A prospective clinical observational study
      of consecutive adult patients after primary external or endonasal surgical DCR,
      both with intubation for nasolacrimal duct obstruction. Nasal endoscopy was used
      at the time of tube retrieval and six months after surgery to evaluate nasal
      pathology and ostium function. RESULTS Sixteen patients were examined. 5/16 (31%)
      had surgically induced nasal synaechiae; in 2/5 patients transnasal synaechiae
      occluded the ostium. Granuloma adjacent to the ostia in 2/16 (12.5%) did not
      impair function. There was no difference in the incidence of synaechiae or
      granuloma after endonasal compared to external DCR. In 3/16 (19%) endoscopy aided
      retrieval of tubes concealed by transnasal synaechiae or a narrow nasal space.
      Six months after surgery ostium function was positive in 12/16 (75%) using the
      functional endoscopic dye test; 13/16 (81%) patients had relief of epiphora with
      patent syringing; one had an alternative drainage route. CONCLUSIONS Nasal
      endoscopy after DCR i) identifies surgically induced nasal mucosal pathology, ii)
      assists in difficult retrieval of tubes and iii) assesses ostium function using
      the functional endoscopic dye test. The information obtained is adding much to
      our understanding of the effects of DCR at the lacrimal / sinus / nasal
      interface. 

PMID- 12045982
TI  - Everting sutures in involutional entropion.
AB  - Involutional entropion is the commonest cause of entropion in the elderly
      population. Many surgical procedures have been described to correct it. The
      everting suture technique is simple and quick and can be undertaken in the clinic
      or even away from a medical setting. However, it has been regarded as a temporary
      cure, especially in the presence of horizontal lower lid laxity. We reviewed the
      results of everting sutures in 55 lids of 50 patients. The minimum follow-up was
      18 months. 78% of patients had no recurrence of their entropion. Our results
      suggest that horizontal eyelid laxity may not be the only major factor in
      recurrent entropion following everting sutures. Dermatochalasis with orbital fat
      prolapse may also contribute. 

PMID- 12045983
TI  - Primary orbital rhabdomyosarcoma in an adult.
AB  - PURPOSE. Rhabdomyosarcoma is the most common primary orbital malignant tumor in
      children. Though rare above the age of twenty, the authors present a case of
      primary orbital rhabdomyosarcoma in an adult and review the literature. DESIGN.
      Clinico-pathologic case report. METHODS. A 34-year-old man presented with a
      recurrent orbital tumor four years after initial excision. This tumor was
      initially misdiagnosed elsewhere as Merkel cell tumor on the basis of spurious
      immunohistochemical studies. Excision biopsy of the recurrent orbital mass was
      performed. MAIN OUTCOME MEASURES. MRI of the orbit and brain was done as well as
      histopathologic examination and immunohistochemistry of the excised mass.
      RESULTS. Histopathologic study of the excised orbital tumor revealed
      rhabdomyosarcoma. CONCLUSION. Careful microscopic evaluation and
      immunohistochemical stains are important in confirming the diagnosis of atypical
      cases of orbital tumors. 

PMID- 12045984
TI  - Teratoid malignant medulloepithelioma of the optic nerve: report of a case and
      review of the literature.
AB  - Medulloepithelioma of the optic nerve is extremely rare and can simulate an optic
      nerve glioma. We report a histopathologically proven medulloepithelioma in a 3
      year-old child with computer tomographic (CT) and magnetic resonance imaging
      (MRI) features. 

PMID- 12045985
TI  - An unusual clinical course of adenoid cystic carcinoma of the lacrimal gland.
AB  - The case of a 25-year-old woman with adenoid cystic carcinoma of the lacrimal
      gland is reported. Her complaints, including pain and localized swelling, first
      started six years earlier. She was diagnosed elsewhere as orbital pseudotumor
      based on clinical and computed tomographic features and was prescribed oral
      corticosteroids. The regimen completely relieved her signs and symptoms, which
      regularly recurred in the ensuing years. When she finally presented with rapidly
      worsening proptosis and pain, she underwent incisional biopsy followed by
      exenteration and 6000 cGy of radiotherapy. This patient is a rare example of
      adenoid cystic carcinoma of the lacrimal gland with an atypical clinical course
      of long duration during which corticosteroids completely suppressed the clinical
      signs and symptoms. 

PMID- 12045986
TI  - Orbital (desmoid type) fibromatosis.
AB  - A case of extra-abdominal fibromatosis (EF) of the orbit is described in a 35
      year-old man presenting with progressive exophthalmos, right ptosis and diplopia.
      MRI showed an orbital mass of intermediate signal in T1-weighted images (WI) and
      low signal in T2WI, which enhanced non-homogeneously after contrast injection.
      The histological diagnosis of EF was made and the lesion was surgically removed.
      No recurrence occurred in 40 months of follow-up. 

PMID- 12045987
TI  - Cicatricial entropion caused by asymptomatic allergic conjunctivitis.
AB  - Cicatricial entropion is an acquired process caused by scarring of the inner
      eyelid with mechanical shortening of the posterior lamella. We present two
      consecutive patients with cicatricial entropion as the heralding sign of allergic
      blepharoconjunctivitis. A 12-year-old girl and a 41-year-old man presented to a
      referral oculoplastics practice with ocular irritation and conjunctival
      symblepharon. Neither patient had a history of allergic ocular symptoms. Slit
      lamp examination revealed marked conjunctival scarring of all four eyelids in
      each patient. Conjunctival scraping and cell staining revealed eosinophils and
      polymorphonuclear leukocytes. No evidence of infection, including Chlamydia and
      Herpes zoster, was detected. Asymptomatic allergic blepharoconjunctivitis should
      be included in the differential diagnosis of cicatricial entropion. Conjunctival
      scraping may be helpful in the diagnosis. 

PMID- 12045988
TI  - Dacryocystorhinostomy in nasolacrimal duct obstruction secondary to sarcoidosis.
AB  - Over the past 3 years we have treated 4 patients with nasolacrimal duct
      obstruction secondary to sarcoidosis. These patients have had mixed outcomes
      following endonasal laser-assisted dacryocystorhinostomy (DCR). A literature
      search from 1966 to the present yielded a further 11 cases of patients thought to
      have sarcoid who underwent DCR. The outcome of these 15 patients indicate that
      while all were initially successful, the subsequent failure rate is high. These
      patients are older than the majority of patients with sarcoidosis and there is a
      female preponderance. Systemic steroids reversed obstruction in one patient. We
      recommend nasal examination in all patients with nasal symptoms in whom DCR is
      proposed to help identify sarcoidosis or other intranasal disease and/or to allow
      treatment of specific diseases prior to surgery. 

PMID- 12045989
TI  - Eyelid molluscum contagiosum in patients with human immunodeficiency virus
      infection.
AB  - PURPOSE. Molluscum contagiosum (MC) is a common viral infection in patients with
      human immunodeficiency virus (HIV) infection. This study aimed to describe the
      relationship between the presentation of MC and the stage of HIV infection as
      measured by T-cell subsets. METHODS. A retrospective study is presented of 11
      patients with MC of the eyelids and HIV infection in whom their CD4+ T
      lymphocytes were determined. RESULTS. Ten patients were in stage C3. The overall
      mean CD4+ count, CD4+ percentage and CD4+/CD8+ ratio were 71.63, 4.37%, and
      0.085, respectively. Seven patients have died of AIDS-related conditions; the
      mean survival time was 12 months and the median 9 months from the diagnosis of
      MC. CONCLUSIONS. MC of the eyelids appears in advanced HIV infection when the
      CD4+ counts are less than 80 cells/&mgr;l. 

PMID- 12045990
TI  - Quality of life outcomes following dacryocystorhinostomy: external and endonasal
      laser techniques compared.
AB  - AIMS/BACKGROUND. Endonasal laser dacryocystorhinostomy (ELDCR) has recently
      become established as an alternative technique to conventional external DCR
      (EXDCR) for relief of epiphora. The aim of this study was to compare quality of
      life and symptomatic outcomes in patients treated by these two methods. METHODS.
      A postal questionnaire was sent to 204 ELDCR and 78 EXDCR patients who had
      undergone surgery under our care more than 6 months previously. The questionnaire
      included the validated 18-item Glasgow Benefit Inventory (GBI) and 5 further
      questions addressing ocular symptomatology. RESULTS. Fully completed
      questionnaires were received from 156 ELDCR and 50 EXDCR patients. Mean GBI
      scores of +16.8 (ELDCR) and +23.2 (EXDCR) were obtained (Mann-Whitney U test =
      NS). Ocular symptom scores were +33 (ELDCR) and +54 (EXDCR) (p=0.005).
      CONCLUSION. Patients undergoing either ELDCR or EXDCR experience significant
      benefit in their healthcare status as detected by the GBI. There is no
      significant difference between the scores obtained by the two groups of patients.
      There were improvements in ocular symptom scores in both groups, with patients
      who had EXDCR scoring significantly better than the ELDCR group. 

PMID- 12045991
TI  - How the most common preservative affects the Meibomian lipid layer.
AB  - PURPOSE Effects of preservatives like benzalkonium chloride on the tear film are
      often hypothetized. With regard to the Meibomian lipid layer only few data are
      available. In order to receive precise information about the effect of
      benzalkonium chloride on the Meibomian lipid layer we performed in vitro
      experiments using a direct optical control of the films. METHODS Meibomian gland
      secretion was spread on a water subphase containing benzalkonium chloride in
      concentrations of 0.001%, 0.005%, 0.01%, 0.05%, and 0.1%, respectively. This
      aqueous subphase was chosen in analogy to the aqueous tear film layer. In our
      experimental assay, the pH was 5.5, the temperature was 20 degrees C. The
      spreading process and the quality of the films were controlled by the Brewster
      Angle Microscope. RESULTS Benzalkonium chloride was well tolerated up to
      concentrations of 0.005%. Concentrations > 0.005% affected the spreading process
      forming domains, and instable films. CONCLUSIONS. Thus it could be demonstrated
      that there is a critical concentration of benzalkonium chloride which destroys
      the spreading and alters the morphology of the Meibomian lipid layer. These
      results were confirmed by a modified method injecting benzalkonium chloride in
      the subphase after spreading the Meibomian lipid layer. Therefore eye drops with
      benzalkonium chloride in concentrations above 0.005% should be abandoned in
      clinical therapy. 

PMID- 12045992
TI  - Erdheim-Chester disease: a bilateral orbital mass as an indication of systemic
      disease.
AB  - A case of bilateral orbital mass and xanthelasma of the eyelids is presented.
      Histology confirmed it to be a form of histiocytosis, possibly an Erdheim-Chester
      disease. This was further confirmed by the presence of a retroperitoneal mass and
      hydronephrosis, which resolved with treatment. A review of the literature on and
      pathological features of this rare fatal disease is presented. 

PMID- 12045993
TI  - Amyloid deposition in the extraocular muscles.
AB  - Orbital involvement is frequent in generalised amyloidosis. However, primary
      localised amyloid in the orbit is rare and requires systemic investigation. We
      present a case with amyloid deposits localised to one extraocular muscle in whom
      systemic investigation has been negative. 

PMID- 12045994
TI  - Acquired lacrimal cyst: a rare entity.
AB  - The case is reported of a 37-year-old woman who complained of a gradually
      progressive mass in the left medial canthus area of one year's duration
      associated with epiphora. Although the clinical and investigative observations
      were suggestive of an acquired lacrimal sac cyst, the diagnosis was clinched by
      the operative and histopathological findings. Excision of the cyst along with
      dacryocystorhinostomy provided complete cure for this patient. 

PMID- 12045995
TI  - Idiopathic intracranial hypertension in patients with Graves' ophthalmopathy.
AB  - We report two cases of idiopathic intracranial hypertension in patients with
      Graves' ophthalmopathy. These patients, with known Graves' ophthalmopathy,
      presented with new onset optic disc edema and preserved visual function. Moderate
      enlargement of the extraocular muscles was observed in one case and moderate
      expansion of the orbital fat volume was observed in the second case. Lumbar
      puncture revealed an elevated opening pressure and normal cerebrospinal fluid
      composition in both patients. Also, no intracranial abnormalities were seen with
      neuroimaging studies. The findings in these patients suggest idiopathic
      intracranial hypertension as a second concurrent diagnosis, and should be
      considered as a possible etiology of optic disc edema in patients with Gravesp
      ophthalmopathy and preserved visual function. 

PMID- 12045996
TI  - Orbital pachymengitis secondary to Pseudomonas aeruginosa.
AB  - Pachymengitis is a very rare disorder that can present with multiple cranial
      neuropathies. The etiology can be inflammatory, infective or a combination of
      both, resulting in a thickening of the cranial dura and an obliteration of the
      individual layers of the meninges. We present a rare case of Pseudomonas
      aeruginosa pachymeningitis in the orbit that resulted in severe and permanent
      visual loss, in a patient after extensive sinus surgery. 

PMID- 12045997
TI  - Malignant melanoma of the choroid presenting as orbital cellulitis: report of two
      cases with a review of the literature.
AB  - Orbital cellulitis can be the initial presentation of malignant melanoma of the
      choroid when such tumors undergo necrosis or extrascleral extension. We report
      two unusual cases of malignant melanoma of the choroid presenting with gradual
      dimness of vision for only two months. Histopathology revealed malignant melanoma
      of the choroid with extensive necrotic hemorrhages within the tumor. There was
      extensive infiltration of the sclera with acute inflammatory cells. No evidence
      of intra- or extrascleral extension by the tumor was seen. Metastatic work-up
      revealed no evidence of secondary deposits. An unusual presentation of malignant
      melanoma of the choroid is reported, together with the pathogenic mechanisms and
      a review of the literature. 

PMID- 12045998
TI  - Sleep disordered breathing in neurologic disorders.
AB  - Wakefulness, NREM sleep, and REM sleep are accompanied by specific changes in
      breathing control, which arise from the interaction of automatic (metabolic,
      involuntary) and behavioural (voluntary and involuntary control systems.
      Considering the complexity in the neuroanatomy and neurophysiology of breathing
      control, it is not surprising that neurologic disorders are frequently
      accompanied by sleep disordered breathing. An introduction on pathophysiology,
      clinical features, diagnosis, and treatment of sleep disordered breathing in such
      diseases as stroke, epilepsy, dementia, spinal cord disease, polyneuropathies,
      and myopathies is presented.

PMID- 12045999
TI  - Severe traumatic brain injury in children--are the results improving?
AB  - QUESTIONS UNDER STUDY: Traumatic brain injury (TBI) remains an important cause of
      mortality and morbidity in children. Medical management is constantly being
      refined, and thus results should improve. The aim of the present study was to
      analyse our data of recent years and to compare them with previous series (1978
      83 and 1988-92). PATIENTS AND METHODS: The data of 51 children (1 month to 16
      years old) with severe blunt TBI treated in our unit from 1994 to 1998 were
      analyzed retrospectively. Severe TBI was defined by immediate loss of
      consciousness and an admission Glasgow coma scale (GCS) <8. Outcome was
      classified by using the Glasgow outcome scale (GOS) 6 to 12 months after injury.
      RESULTS: 35 patients (69%) showed a good outcome (GOS 4 and 5), 14 died (GOS 1),
      one survived in a permanent vegetative state (GOS 2), and another was severely
      disabled (GOS 3) (GOS 1-3 = bad outcome, 31%). Bad outcome was associated with
      low GCS (i.e. 3 and 4), fixed and dilated pupils at admission, invisible basal
      cisterns on first computerized tomography, and presence of coagulopathy. Moderate
      to severe intracranial hypertension was also significantly related to bad outcome
      in the 26 patients with intracranial pressure monitoring. Compared to our first
      series severity of TBI was unchanged, and the incidence of multiple injury and
      consumption coagulopathy was less frequent. Intubation rate prior to admission to
      the centre increased from 35% to 94%. Intensive care measures (duration of
      mechanical ventilation, use of hypothermia, mannitol, thiopentone etc.) were less
      aggressive. The rate of good outcome remained unchanged (69% vs. 60%).
      CONCLUSIONS: Despite changing management policies, results were comparable with
      those of our former series. This fact underlines the importance of primary injury
      and the secondary role of intensive care management on final outcome.

PMID- 12046000
TI  - An evaluation of patient satisfaction amongst family practice patients with
      diverse ethnic backgrounds.
AB  - OBJECTIVE: The aim of this study was to examine the impact of patients' ethnic
      diversity on the patient satisfaction rates. DESIGN: We used the methodology
      developed in an international EUROPE study. The patients were asked to fill in
      self-administered questionnaires on their evaluations of the care received in the
      year prior to the survey. The instrument consists of 23 questions regarding
      specific family physicians' tasks evaluated on a 5 point Likert scale. SETTING:
      Primary care practices of the National Railway Primary Health Care Services in
      Slovenia. STUDY PARTICIPANTS: A questionnaire was handed out to 600 patients
      cared for by 10 physicians. MAIN OUTCOME MEASURES: Percentages of highly
      satisfied patients in groups of patients with different ethnic backgrounds.
      RESULTS: We achieved 65.7% response rate. The overall satisfaction was lower in
      non-Slovenian patients, however was not significant (83.6 vs. 85.8 points, p =
      NS). Non-Slovenian patients were less satisfied with regard to: "quick relief of
      their symptoms", "helping them to feel well so as to be able to perform their
      normal daily activities", physicians'"thoroughness" and their explanations
      concerning what the patients wanted to know about their symptoms and/or illness.
      In a multivariate analysis Slovenian nationality predicted higher patient
      satisfaction with the clinical "performance" of physicians. CONCLUSIONS: As
      family practice remains an important source of primary health care for all
      patients, the providers should address the needs of all members of society
      regardless their social or cultural background. Undergraduate and postgraduate
      curricula have to address communication skills emphasising cultural differences.

PMID- 12046001
TI  - Fluoxetine-induced extrapyramidal symptoms in an adolescent: a case report.
AB  - We present a 15-year-old girl with depression, an obsessive compulsive disorder
      and conduct disorder, who developed EPS (torticollis, bradykinesia and cogwheel
      rigidity) while on fluoxetine. No other cause of EPS was present. The patient
      responded well to benztropine but re-experienced EPS when benztropine was
      stopped. Fluoxetine and benztropine were used concomitantly for 21.2 months and
      the patient has been off medication for 2 months without EPS. This case report
      shows that EPS can and does occur in youth with SSRI. Clinicians should be aware
      of the SSRIs as a potential causative factor for EPS.

PMID- 12046002
TI  - Rabies treatment of health care staff.
AB  - This article deals with post-exposure treatment of contacts of human cases of
      rabies. Experience suggests that rabies is hardly ever transmitted from person to
      person if at all. With the modern generation of vaccines against rabies, the use
      of post-exposure treatment is more widespread. A lot of contacts of patients with
      rabies in developed countries are treated, most of them being health care
      workers. This treatment is however not practised so often in developing countries
      where the supply of highly protective vaccines with a few side effects is low.
      According to reports good hygienic practice in nursing these patients is well
      established.

PMID- 12046003
TI  - Assessment of digital clubbing in medical inpatients by digital photography and
      computerized analysis.
AB  - BACKGROUND: Digital clubbing has been associated with a large number of
      disorders. To overcome the limitation of subjective clinical assessment, several
      objective measurements have been developed among which the hyponychial angle was
      considered most accurate for quantification of finger clubbing. METHODS AND
      RESULTS: Here we investigated hyponychial angles in 123 healthy subjects and 515
      medical inpatients from a tertiary hospital. Healthy subjects had a mean angle of
      178.87 +/- 4.70 degrees (range: 164.78-192.10 degrees ), a finding that is well
      in accordance with previous results obtained using other techniques, underlining
      the accuracy of the chosen method of assessment. The mean angle of patients was
      181.65 +/- 7.18 degrees (range: 162.22-209.19; p <0.0001 compared to healthy
      controls). When the upper limit of normality, i.e. 192.10 degrees, was used to
      define digital clubbing, the prevalence of digital clubbing in our patients was
      8.9%; the percentage of clubbed fingers varied substantially among the various
      disease states (up to 80% in patients with cystic fibrosis). CONCLUSION: The use
      of digital photography with computerised analysis was found to be an easy, fast
      and inexpensive method for the quantification of hyponychial angles with
      excellent intra and inter observer reliability whilst causing no discomfort to
      patients. This tool may therefore be useful in further longitudinal and cross
      sectional studies of finger morphology and may become an accepted standard in the
      diagnosis of digital clubbing.

PMID- 12046004
TI  - The presence of more than two index adenomas is the strongest predictor of
      metachronous colon adenomas.
AB  - QUESTION UNDER STUDY: To assess whether patient or adenoma characteristics at
      index colonoscopy could be predictors of metachronous adenomas and of advanced
      metachronous adenomas at first surveillance colonoscopy. METHODS: This
      retrospective study evaluated polypectomies of 372 adenomas in 214 patients who
      underwent a first follow-up colonoscopy after a median of 17 months. Logistic
      regression analysis was used to assess the association of baseline patient and
      adenoma characteristics with the development of any metachronous adenomas and of
      advanced adenomas (>1.0 cm, or villous component, or severe dysplasia, or early
      cancer). RESULTS: Eighty-one patients (38%) demonstrated 130 metachronous
      adenomas including 21 cases (10%) with advanced adenomas. The presence of more
      than 2 baseline adenomas was significantly associated with the finding of
      adenomas at follow-up (odds ratio 2.44, 95% confidence interval 1.27-4.68, p =
      0.010). Patient age (>or= 60 versus <60) and size of largest adenoma (>1.0 cm
      versus <or= 1.0 cm) demonstrated borderline significance. However, neither
      gender, most advanced histology (tubulo-villous/villous versus tubular), nor most
      advanced dysplasia (severe/early cancer versus mild/moderate) at baseline
      colonoscopy were related with the development of metachronous adenomas.
      Furthermore, none of the analysed patient and polyp characteristics demonstrated
      an association with the development of advanced metachronous adenomas.
      CONCLUSION: Patients with over 2 adenomas at baseline colonoscopy are at highest
      risk for the finding of adenomas at follow-up.

PMID- 12046005
TI  - Use of quality circles among first year medical students and impact on student
      satisfaction.
AB  - Quality circles in the classroom setting are composed of students who meet
      regularly to identify, analyse and solve problems related to a course, and
      implement solutions. We recently instituted quality circles (QCs) among
      preclinical medical students and evaluated their impact on quality of learning
      and student satisfaction. Included in the study were all 135 first-year medical
      students of Trakya University School of Medicine in the 2000-2001 academic year.
      Six students were selected randomly out of 26 volunteers as circle members.
      Circle participants met once a week for 14 45-minute sessions to discuss
      educational issues, propose solutions and prepare a report for submission to the
      dean. A questionnaire was administered to all first-year students and the replies
      provided the problem pool from which the QC chose the problem to be addressed. A
      total of 22 problems concerned education and 28 were identified in the fields of
      accommodation, social activities and other issues. To evaluate the change in the
      perceived quality of learning, circle members prepared a questionnaire designed
      to compare satisfaction at the beginning and end of the study period. This
      questionnaire was composed of 26 items and evaluated various aspects of
      education. There was a significant increase in student satisfaction after the one
      year study period (p = 0.001). In addition to enhancing quality of learning,
      quality circles improved student satisfaction as well. More studies should be
      conducted to test the impact of QCs on education in different settings and
      different classes. Our results show that the use of quality circles in first-year
      medical students improves quality of learning and student satisfaction.

PMID- 12046006
TI  - Absence of age effect on meiotic recombination between human X and Y chromosomes.
AB  - Recombination between the X and Y chromosomes is limited to the pseudoautosomal
      region and is necessary for proper segregation of the sex chromosomes during
      spermatogenesis. Failure of the sex chromosomes to disjoin properly during
      meiosis can result in individuals with a 47,XXY constitution, and approximately
      one-half of these result from paternal nondisjunction at meiosis I. Analysis of
      individuals with paternally derived 47,XXY has shown that the majority are the
      result of meiosis in which the X and Y chromosomes have failed to recombine. Our
      studies of sperm have demonstrated that aneuploid 24,XY sperm have a decreased
      recombination frequency, compared with that of normal sperm. Some studies have
      indicated a relationship of increased paternal age with 47,XXY offspring and with
      the production of XY disomic sperm, whereas others have failed to find such
      relationships. To determine whether there is a relationship between paternal age
      and recombination in the pseudoautosomal region, single-sperm genotyping was
      performed to measure the frequency of recombination between a sex-specific locus,
      STS/STS pseudogene, and a pseudoautosomal locus, DXYS15, in younger men (age < or
      =30 years) compared with older men (age > or =50 years). A total of 2,329 sperm
      cells were typed by single-sperm PCR in 20 men who were heterozygous for the
      DXYS15 locus (1,014 sperm from 10 younger men and 1,315 sperm from 10 older men).
      The mean recombination frequency was 39.2% in the younger men and 37.8% in the
      older men. There was no heterogeneity in the frequency of recombination rates.
      There was no significant difference between the recombination frequencies among
      the younger men and those among the older men, when analyzed by the clustered
      binomial Z test (Z=.69, P=.49). This result suggests that paternal age has no
      effect on the recombination frequency in the pseudoautosomal region.

PMID- 12046007
TI  - Identification of microcephalin, a protein implicated in determining the size of
      the human brain.
AB  - Primary microcephaly (MIM 251200) is an autosomal recessive neurodevelopmental
      condition in which there is a global reduction in cerebral cortex volume, to a
      size comparable with that of early hominids. We previously mapped the MCPH1
      locus, for primary microcephaly, to chromosome 8p23, and here we report that a
      gene within this interval, encoding a BRCA1 C-terminal domain-containing protein,
      is mutated in MCPH1 families sharing an ancestral 8p23 haplotype. This gene,
      microcephalin, is expressed in the developing cerebral cortex of the fetal brain.
      Further study of this and related genes may provide important new insights into
      neocortical development and evolution.

PMID- 12046009
TI  - Residual neuromuscular blockade in the immediate postoperative period.
AB  - Neuromuscular blocking agents are among the most potent and dangerous drugs
      administered in the course of a general anesthetic. Their residual actions can
      have profound effects on a patient's ability to adequately ventilate.
      Understanding the basics of their actions and the methods of monitoring the level
      of neuromuscular blockade will assist the PACU nurse in diagnosing the cause of
      postoperative muscle weakness and hypoventilation. This article will review the
      mechanisms of action and monitoring of neuromuscular blocking agents, as well as
      provide a basic overview of postoperative complications involving hypoventilation
      and motor weakness.

PMID- 12046010
TI  - Hypotension in the PACU: an algorithmic approach.
AB  - Hypotension is a common postoperative complication in the perianesthesia setting
      and contributes to increased patient morbidity and mortality rates. An
      understanding of the etiologies, diagnosis, and treatment of this complication is
      critical to successful treatment of the patient. This article presents an
      algorithm designed to provide the perianesthesia nurse with a step-by-step guide
      to the assessment and management of the patient presenting with hypotension.

PMID- 12046011
TI  - Abdominal aortic aneurysm repair: a look at the first 24 hours.
AB  - Due to the increased prevalence of risk factors associated with abdominal aortic
      aneurysms (AAA) (hypertension, atherosclerotic changes, obesity), surgical
      repairs are more predominant. As a result of changes in surgical techniques and
      issues surrounding ICU overflow and staffing problems, many of these patients
      remain in the PACU for longer periods, often bypassing the ICU altogether. This
      article concentrates on the first 24-hours of postoperative care of a patient
      with an AAA repair. Nursing actions that should be implemented are prioritized,
      and a focus on the common postoperative complications associated with AAA surgery
      is provided.

PMID- 12046012
TI  - Use of complementary and alternative medications by surgical patients.
AB  - Complementary and alternative medication (CAM) use is increasing in popularity
      across the United States. Not surprisingly, health care providers' encounters
      with patients who use these medications are increasing as well. The manufacturing
      and production of CAM are not strictly regulated in contrast to prescription and
      other over-the-counter medications. As such, it is difficult for health care
      providers to assess the likelihood of side effects, toxic effects, or drug-drug
      interactions in the perianesthesia period. Additionally, many patients and
      providers are unaware of the many complications and drug interactions associated
      with CAMs. This study explored CAM use in ambulatory surgical patients at a
      metropolitan, level 1 trauma center in the Southeast. Five hundred patients were
      randomly surveyed regarding CAM use during the 2 weeks before their surgical
      procedure. The frequency of CAM use was assessed and tabulated in relationship to
      potential pharmacodynamic effects and interactions, such as sedation,
      coagulation, blood pressure effects, cardiac effects, electrolyte alterations,
      and potential drug interactions. Descriptive statistics were used to assess
      gender, age, education, ethnicity, and surgery type. This study found that during
      the 2 weeks before surgery, 208 patients (42.7%) consumed CAMs. Ninety-two
      patients (19.8%) took CAMS that inhibit coagulation. Seventy patients (14.4%)
      used CAMs that affect blood pressure, and 36 patients (7.4%) used CAMs with
      cardiac effects. Thirty-nine patients (8%) consumed CAMs with sedative effects.
      The results of this study will assist perianesthesia nurses in patient education,
      preanesthesia patient assessment, and perianesthesia care planning.

PMID- 12046013
TI  - Postoperative nausea and vomiting: understanding the enigma.
AB  - Postoperative nausea and vomiting (PONV) remains one of the most common
      complications related to surgery and anesthesia. Referred to as the "big little
      problem," PONV complications range from minor patient discomfort to gastric
      aspiration or death. There are multiple contributing factors that stimulate the
      vomiting reflex in PONV; yet, no single component is typically the causative
      factor. It usually is a variety of factors that trigger this response. Because
      the causes of PONV are multifactorial, no single antiemetic medication has been
      100% effective for its prevention. A thorough understanding of these factors and
      the pharmacology related to PONV is essential for the effective management of
      this common postoperative complication.

PMID- 12046014
TI  - The use of contact and airborne precautions in the perianesthesia setting.

PMID- 12046015
TI  - Considering bypass of Phase I PACU?

PMID- 12046016
TI  - Grant writing: learning to climb a professional mountain.

PMID- 12046017
TI  - The next generation.

PMID- 12046019
TI  - Choosing between atypical antipsychotics: weighing the risks and benefits.

PMID- 12046020
TI  - Atypical antipsychotics: enhancing healthy outcomes.

PMID- 12046021
TI  - Improving outcomes: clinical and educational challenges for psychiatric nurses.

PMID- 12046022
TI  - Relationship between renal volume growth and renal function in autosomal dominant
      polycystic kidney disease: a longitudinal study.
AB  - In autosomal dominant polycystic kidney disease (ADPKD), renal function remains
      normal for many years into adult life while cysts form and expand progressively,
      starting in childhood. The longitudinal relationships between renal volume
      growth, hypertension, and renal function loss have not been examined in detail.
      At the University of Colorado (Denver, CO), 229 adult subjects with ADPKD
      participated in a longitudinal study from 1985 to 2001. Sequential ultrasound
      examinations were performed at a mean interval of 7.8 +/- 3.1 years (range, 2.6
      to 15.1 years). Renal volume was calculated using a standard formula for a
      modified ellipsoid. The Modified Diet in Renal Disease equation was used to
      calculate glomerular filtration rate (GFR). The mean annual increase in renal
      volume was 46 +/- 55 cm3, and mean annual decline in GFR was 2.4 +/- 2.8
      mL/min/1.73 m2. Men had faster renal growth, more severe hypertension, and a
      faster decline in GFR than women of similar ages. Multiple linear regression
      showed a significant relationship between rate of change in GFR and renal volume
      growth rate, initial renal volume, proteinuria, and age at entry. Correlational
      analysis showed a significant correlation between GFR and renal volume over time
      (R = -0.53) and between follow-up renal volume and follow-up GFR (R = -0.50) for
      both men and women. We conclude that renal volume and rate of renal volume growth
      may be useful markers for disease progression in early stages of ADPKD when GFR
      is preserved.

PMID- 12046023
TI  - Hyperuricemia, hypertension, and proteinuria associated with high-altitude
      polycythemia.
AB  - Chronic exposure to high altitude is associated with the development of
      erythrocytosis, proteinuria, and, in some cases, hyperuricemia. We examined the
      relationship between high-altitude polycythemia and proteinuria and hyperuricemia
      in Cerro de Pasco, Peru (altitude, 4,300 m). We studied 25 adult men with
      hematocrits less than 65% and 27 subjects with excessive erythrocytosis (EE;
      hematocrit > 65%) living in Cerro de Pasco, Peru and compared them with 28
      control subjects living in Lima, Peru (at sea level) and after 48 hours of
      exposure to high altitude. Serum urate levels were significantly elevated in
      patients with EE at altitude, and gout occurred in 4 of 27 of these subjects.
      Urate level strongly correlated with hematocrit (r = 0.71; P < 0.0001). Urate
      production (24-hour urine urate excretion and urine urate-creatinine ratio) was
      increased in this group compared with those at sea level. Fractional urate
      excretion was not increased, and fractional lithium excretion was reduced, in
      keeping with increased proximal reabsorption of filtrate. Significantly higher
      blood pressures and decreased renin levels in the EE group were in keeping with
      increased proximal sodium reabsorption. Serum urate levels correlated with mean
      blood pressure (r = 0.50; P < 0.0001). Significant proteinuria was more prevalent
      in the EE group despite normal renal function. Hyperuricemia is common in
      subjects living at high altitude and associated with EE, hypertension, and
      proteinuria. The increase in uric acid levels appears to be caused by increased
      urate generation secondary to systemic hypoxia, although a relative impairment in
      renal excretion also may contribute.

PMID- 12046024
TI  - Clinicopathologic correlates predict the outcome in children with steroid
      resistant idiopathic nephrotic syndrome treated with pulse methylprednisolone
      therapy.
AB  - Although pulse methylprednisolone therapy (PMT) has been used successfully in the
      management of children with steroid-resistant nephrotic syndrome (SRNS), the
      relationship between initial presenting findings and renal histological
      characteristics to the subsequent clinical response to PMT is unknown. A
      retrospective analysis was conducted in a study cohort of 42 children (30 boys,
      12 girls; mean age, 7.4 +/- 4.7 years) with SRNS administered PMT between June
      1976 and July 1994 at Stanford University (Stanford, CA). Four diagnostic
      categories were created: group I, minimal change disease with or without
      mesangial hypercellularity (n = 10); group II, mesangial proliferation (n = 7);
      group III, focal segmental glomerulosclerosis (FSGS) with or without mesangial
      hypercellularity (n = 10); and group IV, FSGS plus mesangial proliferation (n =
      15). Primary variables analyzed were remission in response to PMT with or without
      alkylating agent therapy and end-stage renal disease (ESRD). Remission rates were
      best in group I (90%) and worst in group IV (46%). With the exception of
      hematuria, presenting clinical features did not correlate with outcome. Segmental
      sclerosis, glomerular adhesion to Bowman's capsule, epithelial sloughing, corona
      (segmental scar surrounded by visceral epithelial cells), subepithelial deposits,
      inflammatory cells, and percentage of interstitium, immunoglobulin M (IgM), IgG,
      and C3 deposition univariately correlated with ESRD in univariate analysis. In a
      multivariate logistic regression model, only segmental sclerosis (P = 0.008)
      correlated with ESRD. Histological analysis is important because it identifies
      features, including segmental sclerosis, that portend a poor prognosis in
      children with SRNS.

PMID- 12046025
TI  - A prospective study of the determinants of renal functional outcome and mortality
      in atherosclerotic renovascular disease.
AB  - Atherosclerotic renovascular disease (ARVD) commonly causes renal failure and
      hypertension and is accompanied by high cardiovascular comorbidity and mortality.
      Interrelationships between these factors remain poorly understood. Patients with
      ARVD presenting to a single center between 1995 and 1999 were followed up, with
      prospective collection of clinical and biochemical data. Fifty men and 48 women
      were identified. Mean age at entry was 68.7 +/- 8.3 (SD) years, and baseline
      creatinine clearance (CrCl) was 35.5 +/- 20.7 mL/min. During follow-up (27.7 +/-
      18.7 months), 10 patients required dialysis therapy, 11 patients underwent
      revascularization, and 35 patients (36%) died. Patients in whom renal function
      deteriorated during follow-up (n = 61) had similar ages, baseline CrCls, blood
      pressures, and comorbidities compared to patients with stable function. Mortality
      (55.7% versus 27.0%; P < 0.01) and proteinuria (protein, 1.3 +/- 1.6 versus 0.3
      +/- 0.4 g/24 h; P < 0.001) were greater in patients with declining function.
      Baseline renal function was not significantly related to blood pressure,
      proteinuria, or change in renal function during follow-up (change in CrCl), but
      patients with a lower CrCl had increased mortality. There was no increase in
      cardiovascular comorbidity in groups with lower renal function. Patients with the
      most severe anatomic ARVD had worse hypertension and increased mortality, but
      severity of ARVD was unrelated to extent of renal dysfunction and proteinuria at
      baseline. Lack of correlation between renal artery anatomy and baseline renal
      function or functional outcome and correlation between renal functional outcome
      and proteinuria suggest that renal parenchymal damage is a major determinant of
      renal dysfunction and outcome in ARVD.

PMID- 12046026
TI  - Goodpasture's disease in the absence of circulating anti-glomerular basement
      membrane antibodies as detected by standard techniques.
AB  - Goodpasture's disease is characterized by rapidly progressive glomerulonephritis,
      often accompanied by pulmonary hemorrhage, in association with deposition of
      antibodies in a linear pattern on the glomerular basement membrane (GBM). The
      diagnosis of Goodpasture's disease in patients with acute renal failure often
      relies on the use of immunoassays to detect circulating anti-GBM antibodies in
      serum samples. We describe three cases of Goodpasture's disease in which no
      circulating anti-GBM antibodies were detectable in serum by well-established
      enzyme-linked immunosorbent assay or Western blotting techniques. The diagnosis
      of Goodpasture's disease was confirmed by renal biopsy, with linear deposition of
      immunoglobulin along the GBM and crescentic glomerulonephritis. In addition, an
      alternative method of antibody detection using a highly sensitive biosensor
      system confirmed that circulating antibodies were present in sera from both
      patients tested. Because this technique is not routinely available for the
      detection of anti-GBM antibodies, we suggest that diagnosis always be confirmed
      with a renal biopsy, and despite negative serological test results using
      immunoassay, the diagnosis of Goodpasture's disease should still be considered in
      the correct clinical context.

PMID- 12046027
TI  - Glomerular tip lesion in minimal change nephropathy: a study of autopsies before
      1950.
AB  - The clinical significance of the glomerular tip lesion, characterized by podocyte
      prominence, capsular adhesion, and/or intracapillary foam cells at or adjacent to
      the urinary pole, remains unclear. It has been postulated that this lesion simply
      represents a response to heavy proteinuria, and cases of nephrotic syndrome with
      tip lesions, but no other histological abnormalities, may represent a form of
      minimal change nephropathy (MCN). However, others have reported that such lesions
      have a clinical course similar to that of primary focal segmental
      glomerulosclerosis (FSGS), and the tip lesion often is included among
      histological variants of FSGS. To determine whether tip lesions may be seen in
      MCN, we examined histological slides of kidneys from pre-1950 autopsies of
      patients with a diagnosis of lipoid nephrosis, a term that at that time comprised
      MCN and FSGS. Before the introduction of antibiotics and corticosteroid therapy,
      patients with nephrotic syndrome frequently died of sepsis. Eight such cases,
      with autopsies performed from 1924 to 1943, were identified in which no glomeruli
      had changes typical of classic FSGS or membranous nephropathy. More than 400
      glomeruli were present in each case. Patient ages ranged from 3 to 45 years (six
      patients <11 years), all had marked edema (duration, 2 weeks to 21 months) and
      heavy proteinuria, and each died of sepsis and/or pneumonia (pneumococcal in six
      patients). Glomerular tip lesions were found in five of these eight cases (range,
      3 to 26 lesions per case; 0.3% to 4.4% of total glomeruli present), with no
      predilection for the deep, middle, or superficial cortex. No tip lesions were
      seen in kidneys from autopsies of age-matched patients without a history of
      glomerular disease. These findings suggest that the glomerular tip lesion can
      occur in MCN and most likely represents a response to heavy proteinuria that is
      not disease specific.

PMID- 12046029
TI  - Albumin to creatinine ratio: a screening test with limitations.
AB  - The aim of this study is to assess the effects of age on (1) the ability of a
      spot albumin-creatinine ratio (ACR) to accurately predict 24-hour albumin
      excretion rate (AER), and (2) the performance of spot ACR as a screening test for
      microalbuminuria. Three hundred fourteen patients with diabetes aged 18 to 84
      years attending a tertiary outpatient clinic underwent one 24-hour urine
      collection and, immediately after completion, provided one fasting spot morning
      urine sample. Twenty-four-hour AER and spot ACR were determined. Performance of
      spot ACR was assessed according to age and sex. Fifty-three percent of men and
      32% of women had an AER of 20 microg/min or greater. Multiple regression analysis
      showed age was an independent predictor of spot ACR. For an AER of 20 microg/min
      for patients in the age range of 40 to 80 years, there was an increase in
      corresponding values for spot ACR from 18.2 mg/g (95% confidence interval [CI],
      15.6 to 21.3) to 32.5 mg/g (95% CI, 27.5 to 38.4) in men and from 22.1 mg/g (95%
      CI, 18.0 to 27.1) to 56.4 mg/g (95% CI, 47.2 to 67.4) in women. Using ACR cutoff
      values of 22.1 mg/g or greater and 30.9 mg/g or greater in conventional units
      (equivalent to > or =2.5 and > or =3.5 mg/mmol in SI units) in men and women, the
      spot ACR provided high sensitivities (men, 95.7%; women, 93.35%) and had
      excellent receiver operator characteristic curves, respectively. However, the
      spot ACR false-positive rate increased with age from 15.9% (age, 40 to 65 years)
      to 31.8% (>65 years) in men and from 10.5% (age, 45 to 65 years) to 28.3% (>65
      years) in women. Spot ACR is a good screening test for microalbuminuria, but a
      poor predictor of quantitative AER, and should not be used as a diagnostic test.
      The increase in spot ACR relative to 24-hour AER with age supports the use of sex
      and age-adjusted ACR cutoff values.

PMID- 12046028
TI  - Antiendomysial antibodies in Berger's disease.
AB  - The finding of increased levels of immunoglobulin A (IgA) against food antigens
      in patients with IgA nephropathy prompted the hypothesis of an association
      between IgA nephropathy and celiac disease (CD). Attention was initially directed
      to antigliadin antibodies, then to IgA antiendomysial antibodies (IgA-EMA). IgG1
      EMA have been found in patients with CD with IgA-EMA-negative results. The
      presence of IgA- and IgG1-EMA was investigated in 36 patients with IgA
      nephropathy, 15 patients with other primary glomerulonephritis, and 15 patients
      with lupus nephritis. IgA-EMA and IgG1-EMA were detected by indirect
      immunofluorescence analysis. At the time of renal biopsy, the following factors
      were evaluated: history of macroscopic hematuria, serum creatinine level,
      urinalysis, 24-hour proteinuria, blood pressure, and histological classification
      of IgA nephropathy. Sixteen of 36 patients with IgA nephropathy (44.4%) showed
      EMA positivity. Among patients with positive EMA, 12 patients (75%) were IgG1-EMA
      positive, 2 patients (12.5%) were IgA-EMA positive, and 2 patients (12.5%) were
      positive for both isotypes. No significant differences were observed between the
      two groups (EMA positive versus EMA negative) concerning age, serum creatinine
      level, macroscopic hematuria, blood pressure, 24-hour proteinuria, or degree of
      renal histological involvement. IgA- and IgG1-EMA were not detected in patients
      with other primary nephropathies or lupus nephritis. These results, based on the
      finding of IgG1-EMA, suggest a common pathogenetic pathway for CD and IgA
      nephropathy. On this basis, the presence of IgG1-EMA and/or IgA-EMA should be
      investigated in patients with IgA nephropathy. Furthermore, the role of a gluten
      free diet in the natural history of IgA nephropathy, at least in EMA-positive
      patients, needs to be ascertained.

PMID- 12046030
TI  - Dipstick proteinuria: can it guide hypertension management?
AB  - Recent guidelines call for lower blood pressure targets in patients with
      proteinuria of 1 g/d or greater. Dipstick test for proteinuria is widely
      available, but no information on its sensitivity or specificity is available when
      implementing current guidelines. To determine performance characteristics of
      dipstick proteinuria, we studied 332 patients attending a Veterans Administration
      renal clinic who underwent simultaneous measurement of urine protein and
      creatinine, as well as automated urinalysis with a dipstick graded from 0 to 4+
      with a machine reader. There was increasing severity of proteinuria with each
      increment in dipstick result. When the spot urine protein-creatinine ratio was
      less than 1, a lower specific gravity was associated with greater severity of
      proteinuria. Areas under the receiver operating characteristic curve for 1 and 3
      g protein/g creatinine were 0.945 and 0.905, respectively. This attests to the
      excellent performance of the urine dipstick. The likelihood of having a protein
      creatinine ratio of 1 or greater was 7% when urine dipstick protein value was 1+
      or 2+, 62% when dipstick protein value was 3+, and 92% when dipstick protein
      value was 4+. Thus, dipstick proteinuria assessed by an automated reader remains
      a useful test to predict the severity of proteinuria and can be used to guide
      therapy. A cutoff dipstick proteinuria value of 3+ has the best combination of
      sensitivity and specificity (96% and 87%, respectively) in predicting a protein
      creatinine ratio of 1 or greater and a cutoff value of 4+ in predicting a protein
      creatinine ratio of 3 or greater (sensitivity, 94%; specificity, 83%). These
      results suggest that patients with 3+ or greater proteinuria should not only
      trigger appropriate evaluation of proteinuria, but also have mean arterial
      pressures targeted to less than 92 mm Hg.

PMID- 12046031
TI  - Studies of prognostic factors in end-stage renal disease: an epidemiological and
      statistical critique.
AB  - We reviewed prognostic studies for patients treated with renal replacement
      therapy by using an electronic database and bibliographic review for 1990 to
      1998. Using the inclusion criteria of English language, adult patients, primary
      article, minimum 50 patients, primary focus on prognostic factors, and mortality
      outcome, 104 articles were identified. The 104 articles were reviewed for eight
      epidemiological and seven statistical criteria that addressed the scientific
      validity and interpretability of results. The following percentages of the 104
      articles satisfied each of the eight epidemiological criteria: (1) a priori
      hypothesis, 6%; (2) zero time specified, 49%; (3) prognostic factors collected
      before zero time, 69%; (4) inception cohort, 59%; (5) control for treatment, 74%;
      (6) operational criteria, 82%; (7) missing variables reported, 12%; and (8) loss
      to follow-up reported, 42%. Summary analysis showed that 76% of studies satisfied
      four or fewer of the eight identified criteria. In the 77 articles (74%) that
      used the Cox proportional hazards model, the following percentages of articles
      met each of the seven statistical criteria: (1) proportional hazards verified,
      26%; (2) censoring explained, 57%; (3) multivariate analysis performed, 91%; (4)
      significance levels given, 99%; (5) age adjusted, 95%; (6) diabetes adjusted,
      66%; and (7) cardiac adjusted, 44%. Summary analysis found that 47% of the 77
      studies satisfied four or fewer of the seven identified criteria. Superficially,
      results appear to show that when the Cox proportional hazards model was used,
      statistical analysis was better than the epidemiological design. However, studies
      we examined had serious defects in both epidemiological design and statistical
      analysis. The consequent validity of results for the quantification of prognostic
      factors is questionable.

PMID- 12046032
TI  - Arterial wall properties in patients with renal failure.
AB  - Hemodialysis (HD) patients commonly show abnormalities of the arterial system.
      Only a few studies have focused on arterial wall properties in patients with
      early stages of renal insufficiency and patients on peritoneal dialysis (PD)
      therapy. In this study, the distensibility coefficient (DC), a marker of arterial
      stiffening and intima media thickness (IMT) of the common carotid artery (CCA)
      and a surrogate marker of atherosclerosis, was assessed in four age-matched
      groups of patients: 18 HD patients, 36 PD patients, 30 patients with chronic
      renal failure (CRF) not yet on dialysis therapy with a creatinine clearance (CCl)
      between 10 and 70 mL/min, and 25 normotensive controls with normal renal
      function. Arterial wall properties were assessed by an automated vessel wall
      detection system. In patients with CRF and HD patients, but not PD patients, the
      DC of the CCA was significantly reduced (P < 0.05) compared with controls (CRF,
      12.6 +/- 7.5 10(-3)/kPa; HD, 11.6 +/- 7.6 10(-3)/kPa; and PD, 14.7 +/- 6.2 10(
      3)/kPa compared with controls, 16.7 +/- 4.6 10(-3)/kPa). In patients with CRF, a
      significant relationship was found between CCl and the DC (r = 0.41; P = 0.02).
      IMT was not different among patients with CRF (589 +/- 115 microm), HD (622 +/-
      115 microm) and PD patients (585 +/- 121 microm), and controls (668 +/- 150
      microm). In conclusion, compared with controls, the DC of the CCA was
      significantly reduced in HD patients and those with CRF, but not PD patients. In
      patients with CRF, the DC correlated significantly with CCl. IMT did not differ
      between groups of renal patients and controls.

PMID- 12046033
TI  - Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin
      in hemodialysis patients.
AB  - A 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor is recommended in
      hemodialysis (HD) patients with hypercholesterolemia to improve their lipid
      profiles. We evaluated effects of simvastatin on markers for inflammation,
      oxidative stress, and coagulation in HD patients. Sixty-two maintenance HD
      patients with serum cholesterol levels of 200 mg/dL or greater were randomly
      assigned to the treatment group (n = 31; 8 men, 23 women; age, 63 +/- 11 years)
      and administered simvastatin, 20 mg/d, for 8 weeks or to the control group (n =
      31; 10 men, 21 women; age, 60 +/- 12 years). We measured cholesterol, albumin,
      high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA; an index of
      lipid peroxidation), and D-dimer (a marker of intravascular coagulation) in blood
      at baseline and again at 8 weeks. Fifty-eight of 62 patients completed the study.
      In the control group, total cholesterol, serum albumin, hs-CRP, MDA, and D-dimer
      levels did not change. In the treatment group, simvastatin administration for 8
      weeks significantly reduced total cholesterol levels from 232 +/- 25 to 165 +/-
      39 mg/dL (P < 0.001) and hs-CRP levels from a median of 0.23 mg/dL (range, 0.05
      to 1.63 mg/dL) to 0.12 mg/dL (range, <0.006 to 1.45 mg/dL; P < 0.01), whereas it
      increased serum albumin levels from 3.4 +/- 0.3 to 3.6 +/- 0.4 g/dL (P < 0.001).
      Administration of simvastatin did not affect MDA and D-dimer levels. These
      results suggest that in addition to the lipid-lowering effect, simvastatin had an
      antiinflammatory effect in HD patients. Considering that atherosclerosis is
      inflammation of the vascular wall, simvastatin may have a beneficial effect on
      cardiovascular disease, in part because it alleviates inflammation.

PMID- 12046034
TI  - Native arteriovenous fistula: preoperative evaluation.
AB  - Duplex sonography recently has been recognized as an objective and noninvasive
      method to assess morphological and functional parameters of vessels that could
      predict arteriovenous fistula (AVF) patency and time of adequate maturation. To
      prospectively study prognostic indicators of native AVFs, forearm arteries and
      veins of patients with end-stage renal disease were examined by duplex sonography
      before AVF construction. Several anatomic parameters, including feeding artery
      internal diameter (IDA), resistance index (RI), and arterial blood flow (Q(A))
      before and at reactive hyperemia (RH) and internal diameter of the vein (IDV)
      before and after proximal vein compression (PVC), were measured. Measurements of
      the feeding artery were repeated at different periods after native AVF
      construction. One hundred sixteen patients were included on the study. The
      primary patency rate (successful constructed AVF) of native AVFs was 80.2%. In
      this group, mean values for IDA were 0.264 cm; RI at RH, 0.50; and Q(A), 54.5
      mL/min. IDV increased after PVC for 59.3%. In the group with failed AVFs (19.8%),
      mean IDA was 0.162 cm; RI at RH, 0.70; and Q(A), 24.1 mL/min. IDV increased after
      PVC for only 12.4%. Patency rates after surgery in a group with IDAs greater than
      0.16 cm was 93%, and with IDAs of 0.16 cm or less, 32%. In a group with RIs at RH
      less than 0.7, the patency rate was 95.3%, and with RIs of 0.7 or greater, 38.7%.
      An AVF feeding artery Q(A) of 300 mL/min was achieved in the group with IDAs
      greater than 0.16 cm, those with RIs at RH less than 0.7 after 1 week, those with
      IDAs of 0.16 cm or less between 3 and 8 weeks, and those with RIs of 0.7 or
      greater between 8 and 12 weeks. This study shows that duplex sonography may
      provide useful data on preoperative morphological and functional characteristics
      of vessels used for AVF construction. Increase in IDA, Q(A), RI at RH, and IDV
      after PVC are important to predict AVF primary patency rate. Based on these
      measurements, the most adequate location for AVF construction, as well as time of
      optimal AVF development, can be determined, particularly for patients at greater
      risk for primary failure, such as the elderly and patients with diabetes.

PMID- 12046035
TI  - A comparison of standardized versus "usual" blood pressure measurements in
      hemodialysis patients.
AB  - Hypertension is very common and contributes to the high cardiovascular morbidity
      in patients undergoing chronic hemodialysis therapy. However, the accuracy of
      blood pressure measurement in this population has not been well studied. We
      conducted a cross-sectional study of 270 patients at seven outpatient
      hemodialysis units. Predialysis and postdialysis seated blood pressure readings
      obtained by the dialysis unit using automated blood pressure monitors were
      significantly higher than readings obtained by a research nurse following
      standard procedures for blood pressure measurement (14.3/7 mm Hg higher
      predialysis; P < 0.01; 13.6/4.4 mm Hg higher postdialysis; P < 0.05). In 55% of
      patients, the postdialysis systolic blood pressure measured in the dialysis unit
      was at least 10 mm Hg higher than the standard reading. Bland-Altman analyses
      indicated poor agreement between the two readings. This study shows a marked
      discrepancy between routine dialysis unit and standardized blood pressure
      measurements. Blood pressure is frequently overestimated by routine dialysis unit
      readings. In light of these findings, efforts should be made to standardize blood
      pressure readings in hemodialysis units based on American Heart Association
      recommendations for blood pressure measurement.

PMID- 12046036
TI  - Correction of discrepancy between prescribed and actual blood flow rates in
      chronic hemodialysis patients with use of larger gauge needles.
AB  - The blood flow rate delivered by the dialysis machine (d-BFR) may not be
      accurately reflected by the blood flow rate set on the machine (sm-BFR). High
      negative arterial pressure may lead to deformity of the blood pump-segment
      tubing, resulting in a lower stroke volume and d-BFR. The Hagen-Poiseuille law
      predicts that the use of larger gauge needles should make arterial pressure less
      negative. Twenty-two patients on chronic hemodialysis therapy with a percentage
      of reduction in urea (PRU) levels less than 65% and/or a greater than 10%
      difference between sm-BFR and d-BFR underwent dialysis using one-gauge larger
      arterial and venous needles. d-BFR increased by 23 +/- 5 mL/min. Arterial
      pressure became less negative by 58 +/- 5 mmHg, and venous pressure decreased by
      31 +/- 7 mm Hg. Changes in arterial and venous pressures allowed sm-BFR to be
      increased to 500 mL/min in all 22 patients, resulting in an increase in d-BFR of
      83 +/- 7 mL/min. This translated into an increase in PRU of 5% +/- 0.01%. All
      results were significant at P < 0.001. A survey showed that less than 5% of
      needles used in our region were 14 G. This study shows that the use of larger
      gauge needles can significantly increase d-BFR and PRU as a result of changes in
      arterial and venous pressures, resulting in a significantly increased dialysis
      dose at no additional cost.

PMID- 12046037
TI  - Patient satisfaction with care and behavioral compliance in end-stage renal
      disease patients treated with hemodialysis.
AB  - Compliance with the hemodialysis (HD) prescription is an important predictor of
      patient outcome. Although there is interest in the concept of patient
      satisfaction with medical care and caregivers, relatively few such data exist
      regarding HD patients. We examined whether associations exist between patient
      satisfaction with medical personnel and depressive affect and social support
      levels and behavioral compliance with prescribed HD treatment. Seventy-nine HD
      patients were interviewed, assessing depression, social support, and perception
      of satisfaction with dialysis staff. Medical and treatment data, Karnofsky
      functioning and severity of illness scores, and behavioral and laboratory
      compliance measures were determined. There was no association between patient
      satisfaction with care and level of depressive affect. A relationship was found
      between patient satisfaction with care with their nephrologist and attendance at
      dialysis sessions. Patients who had a poor perception of satisfaction with their
      nephrologist had poorer attendance at dialysis sessions. There was no
      relationship between behavioral compliance and patient perception of ancillary HD
      staff. In addition, patient perception of satisfaction with staff was related to
      perception of social support, protein catabolic rate, and serum albumin
      concentration, all of which have been linked to survival. We conclude that a
      nephrologist has a crucial role in patient compliance. These results suggest
      interventions that improve patient perception of physician support may improve
      patient adjustment and possibly survival.

PMID- 12046038
TI  - Risk factors and risk for mortality of mild hypoparathyroidism in hemodialysis
      patients.
AB  - Relative hypoparathyroidism (parathyroid hormone [PTH] < or = 200 pg/mL) is
      prevalent in hemodialysis (HD) patients, with unknown pathogenesis and prognosis.
      Thus, to clarify risk factors and prognosis of time-dependent relative
      hypoparathyroidism in HD patients, a retrospective cohort study was performed for
      126 HD patients with four or more PTH determinations and no previous total or
      subtotal parathyroidectomy. Values for intact PTH, ionized calcium, phosphate,
      magnesium, albumin, creatinine, urea reduction ratio (URR), glucose, hemoglobin
      A1c (HbA1c), aluminum, and 1,25(OH)2D were obtained at enrollment and at some
      time during follow-up. The prevalence of relative hypoparathyroidism at entry was
      76 of 126 patients (60.3%). Univariate analysis showed that patients with
      hypoparathyroidism were older, more likely to have diabetes, and had greater
      ionized calcium levels and lower phosphate, albumin, blood urea nitrogen (BUN),
      and creatinine levels. Patients with diabetes were older and had a shorter
      duration of dialysis therapy and lower PTH, phosphate, albumin, BUN, and
      creatinine levels and URRs. Conversely, multivariate analysis showed that PTH
      levels at entry were associated directly with creatinine levels and inversely
      with age and ionized calcium levels (but not diabetes). During follow-up, PTH
      levels fluctuated concomitantly with ionized calcium and phosphate levels over
      time in all patients. Time-dependent PTH levels were associated directly with
      duration of dialysis therapy and use of vitamin D and phosphate and albumin
      levels, but inversely with age and ionized calcium and magnesium levels (but not
      glucose or HbA1c levels). Interestingly, time-dependent PTH levels were
      independently associated with survival after adjusting for traditional risk
      factors (diabetes, age, albumin and creatinine levels, and URR) and duration of
      dialysis therapy. We conclude that in HD patients, relative hypoparathyroidism
      was not associated with diabetes per se. Time-dependent PTH levels were
      associated with age, duration of dialysis, and levels of ionized calcium,
      phosphate, albumin, and magnesium. Moreover, relative hypoparathyroidism at entry
      and lower time-dependent PTH levels predict mortality.

PMID- 12046039
TI  - Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in
      hemodialysis patients.
AB  - It is well known that genetic factors are involved in the progression of
      secondary hyperparathyroidism (HPT) in hemodialysis (HD) patients. The purpose of
      the present study is to determine the relationship between restriction fragment
      length polymorphisms (RFLPs) of the parathyroid hormone (PTH) gene and serum
      intact PTH levels in HD patients. Eighty-six HD patients not treated with vitamin
      D and 80 healthy controls were analyzed. PTH genotypes were determined by
      polymerase chain reaction and RFLPs of BstBI and DraII. The presence or absence
      of BstBI and DraII restriction sites of the PTH gene were indicated by B or b and
      D or d, respectively. There were no significant differences in frequencies of
      each genotype between HD patients and healthy controls. In HD patients, serum
      intact PTH levels in the Dd/dd genotype were significantly greater than those in
      the DD genotype (P < 0.02). However, there was no significant difference in serum
      intact PTH levels between Bb/bb and BB genotypes. Serum intact PTH levels in the
      non-BBDD haplotype were significantly greater than those in the BBDD haplotype (P
      < 0.01). Serum intact PTH levels correlated negatively with serum calcium (Ca)
      and magnesium (Mg) levels and positively with alkaline phosphatase levels in
      simple regression analysis. However, in forward stepwise multiple regression
      analysis, only serum Ca and Mg levels predicted serum intact PTH levels. We
      conclude that PTH genotypes may influence secondary HPT in HD patients.

PMID- 12046040
TI  - Impaired secretion of parathyroid hormone, but not refractoriness of osteoblast,
      is a major mechanism of low bone turnover in hemodialyzed patients with diabetes
      mellitus.
AB  - Diabetic bone disease is characterized by low bone turnover resulting from either
      impaired secretion of parathyroid hormone (PTH) or refractoriness of osteoblasts
      to PTH. The present study was performed to elucidate which factor contributes
      more to the reduction in bone turnover by comparison between 64 hemodialyzed
      patients with diabetes mellitus and 106 hemodialyzed patients without diabetes
      mellitus. Only men were enrolled to avoid the influence of the menstrual cycle on
      bone metabolism. Serum intact PTH (iPTH) levels were significantly lower in
      hemodialyzed patients with diabetes than those without diabetes, although no
      significant difference existed in age, duration of hemodialysis therapy, or serum
      calcium or phosphate levels. Of the biochemical markers measured, serum intact
      osteocalcin (iOC) and deoxypyridinoline levels were significantly lower in
      patients with diabetes, although serum bone-specific alkaline phosphatase (BAP)
      and pyridinoline levels did not differ significantly between the two groups of
      patients. When patients were restricted to those with serum iPTH levels greater
      than 180 pg/mL, this parameter correlated significantly in a positive manner with
      both serum iOC and BAP levels and negatively with bone mineral density at distal
      radius 1/3. Regression slopes between iPTH levels and these parameters were not
      significantly different between the two groups of patients, indicating the
      absence of refractoriness of bone to PTH in patients with diabetes. In
      conclusion, our findings suggest that impaired PTH secretion, but not
      refractoriness of osteoblasts to PTH, may be responsible for the low bone
      turnover in hemodialyzed patients with diabetes.

PMID- 12046041
TI  - Analysis of renal bone disease treatment in dialysis patients.
AB  - End-Stage Renal Disease Network 11 initiated a renal osteodystrophy quality
      improvement activity in 1999. One component was the collection and assessment of
      dialysis facility renal osteodystrophy protocols, whereas another component was
      the analysis of bone disease-related medication use. Two hundred eighty-eight
      facilities were invited to submit protocols. A model bone disease and mineral
      metabolism protocol was developed as the standard for comparison. From the model
      protocol, an instrument was created to evaluate eight key areas (baseline
      screening of key laboratory data, dietary intervention, phosphate-binder use,
      vitamin D use, monitoring of key laboratory indicators, management of
      hypercalcemia, oversuppression of parathyroid hormone [PTH], and guidelines for
      both hemodialysis and peritoneal dialysis patients). A bone disease-related
      prescription survey was completed for 749 randomly selected patients. Survey
      information included vitamin D and phosphate-binder use and related laboratory
      values (calcium, phosphorus, intact PTH [iPTH], and calcium x phosphorus
      product). Although 45% of facilities had six or more points on the evaluation
      tool, protocols were still incomplete compared with the model. Mean facility
      specific scores among the five states in the Network ranged from 1.0 to 5.9
      (possible scores, 0 to 8). Most patients were prescribed a phosphate binder;
      however, 31.8% had average phosphorus levels greater than 6.0 mg/dL during the 3
      month period. Only 58% of patients with average iPTH concentrations greater than
      260 pg/mL were prescribed vitamin D. Of patients treated with vitamin D, 39% had
      iPTH concentrations less than 130 pg/mL. There is opportunity to improve renal
      osteodystrophy protocols in Network 11 and reinforce potential hazards of
      sustained hyperphosphatemia and hyperparathyroidism.

PMID- 12046042
TI  - Patterns of infection in patients maintained on long-term peritoneal dialysis
      therapy with multiple episodes of peritonitis.
AB  - The causes of peritonitis in patients with end-stage renal disease maintained on
      long-term peritoneal dialysis (PD) are unclear. One possible explanation for
      peritonitis, particularly in patients with multiple episodes of infection, is the
      release of planktonic bacteria from biofilm on the walls of catheters. Bacteria
      form biofilm on the walls of catheters within 48 hours of their placement. If
      this explanation were correct, one would expect there to be reappearance of
      organisms causing infection in patients with multiple episodes of peritonitis.
      The charts of all patients starting long-term PD at New Haven CAPD from January
      1, 1990, through July 31, 2000, were reviewed. Patients were included in the
      study if they had experienced more than one episode of culture-positive
      peritonitis and complete data were available concerning cultured organisms and
      antibiotic sensitivity patterns. Episodes of infection, organisms, and
      sensitivities and catheter changes were reviewed. Of 630 patients, 198 were
      identified as meeting these criteria. There were 114 men; 104 patients were
      white. Of 198 patients, 157 (80%) had at least one repeat infection with the same
      organism. In 124 (79%) patients, more than 50% of the peritonitis episodes were
      caused by the same organism. Of 90 patients who had more than four episodes of
      infection in their history, 59 (65%) had at least half or more of their episodes
      caused by the same organism. Sequential analyses for independence revealed that
      for Staphylococcus epidermidis and for Staphylococcus aureus, there was a
      significantly increased likelihood for these organisms to follow themselves as
      causative organisms of peritonitis. When the data were analyzed using the
      Spearman correlation test, the results indicated that the likelihood of repeat
      infections occurring was significantly greater than by chance alone. Of 67
      patients with catheter changes and subsequent peritonitis, only 10 (15%)
      developed repeat infections with the same organism after the catheter change.
      Eight of these were due to yeast. These data support the hypothesis that
      bacterial biofilm on the walls of peritoneal catheters may be associated with
      peritonitis in patients maintained on long-term PD and may contribute to at least
      some of these episodes of infection.

PMID- 12046043
TI  - Dialysis adequacy and transport test for characterization of peritoneal transport
      type in Chinese peritoneal dialysis patients receiving three daily exchanges.
AB  - Dialysis adequacy and transport test (DATT) is an accurate method to classify
      peritoneal transport type for continuous ambulatory peritoneal dialysis (CAPD)
      patients with a regimen of four exchanges of 2 L/d. We examined the accuracy of
      DATT for the characterization of peritoneal transport type in patients with a
      regimen of three exchanges of 2 L/d, which is the standard CAPD regimen in Hong
      Kong Chinese. We studied 189 adult Chinese CAPD patients with a prescription of
      three exchanges of 2 L/d. Patients who had a peritonitis episode within the
      previous 30 days were excluded. Standard peritoneal equilibration test (PET) and
      DATT were performed on consecutive days. Correlation coefficients between
      dialysate-to-plasma ratios of creatinine (D/P) obtained for the PET and the DATT
      was 0.698 (P < 0.001). Peritoneal transport type was classified according to the
      reported D/P creatinine reference values obtained from the PET at 4 hours. When
      the result was compared with the transport type classified by the DATT result
      using the linear regression formula derived, the Cohen kappa was 0.433 (95%
      confidence interval, 0.329 to 0.537), which could be regarded as a moderate level
      of agreement. For classification of the low transporters, the specificity of DATT
      was 90.1%, and sensitivity was 72.3%. For classification of the high
      transporters, the specificity of DATT was 96.6%, and sensitivity was 57.1%. DATT
      and PET had a reasonable agreement in the classification of peritoneal transport
      type for Chinese CAPD patients receiving a daily schedule of three exchanges of 2
      L/d. Although DATT may be less accurate for CAPD patients with three daily
      exchanges, it remains a specific method to identify low and high transporters.

PMID- 12046044
TI  - Prevalence of constipation in continuous ambulatory peritoneal dialysis patients
      and comparison with hemodialysis patients.
AB  - Many hemodialysis patients suffer from constipation. The frequency of
      constipation has not been rigorously evaluated in continuous ambulatory
      peritoneal dialysis (CAPD) patients, however. We conducted a survey on
      constipation in CAPD patients and compared the findings with those in
      hemodialysis patients through a questionnaire. Daily dietary fiber and potassium
      intake were calculated from the patients' dietary records. In the questionnaire,
      patients were asked about bowel frequency, stool consistency, straining, and use
      of laxatives and resins. The frequency of constipation was 28.9% in 204 CAPD
      patients and 63.1% in 268 hemodialysis patients. The hemodialysis patients had a
      3.14 times higher relative risk of constipation than the CAPD patients. Only 3.4%
      of CAPD patients needed resin to avoid hyperkalemia. Of hemodialysis patients,
      49% needed resin. Among the 261 hemodialysis patients, 205 (78.5%) suppressed an
      urge to defecate during hemodialysis therapy. Potassium and total dietary fiber
      intake per day were 1.8 +/- 0.5 g and 11.0 +/- 4.0 g in CAPD patients, which were
      higher (P < 0.01) than the values in hemodialysis patients--1.3 +/- 0.5 g and 5.9
      +/- 2.7 g. The results suggest that constipation occurs less frequently in CAPD
      patients than in hemodialysis patients. The low rate of constipating drug
      administration, dialysis modality-based lifestyle, and higher total dietary fiber
      intake may cause the lower prevalence of constipation in CAPD patients.

PMID- 12046045
TI  - Assessment of quality of life after simultaneous pancreas-kidney transplantation.
AB  - It is unclear if simultaneous pancreas-kidney (SPK) transplantation adds to the
      general quality of life (QOL) achieved with kidney transplantation alone (KTA).
      This case-controlled study matched 27 successful SPK transplant recipients with
      27 successful KTA recipients. Cases were matched for gender, age (+/- 7 years),
      and year of transplant (+/- 2 years). Both groups had type 1 diabetes and end
      stage renal disease. Diabetes-related QOL was assessed using the Diabetes Quality
      of Life (DQOL) questionnaire. General QOL was assessed using Medical Outcome
      Health Survey Short Form-36 (SF-36) and Quality of Well Being (QWB)
      questionnaires. Morbidity data were obtained through chart review. There was a
      trend for a lower prevalence of coronary artery disease (5 of 27 versus 13 of 27)
      and peripheral vascular disease (5 of 27 versus 9 of 27) in SPK recipients (P =
      not significant). Satisfaction with diabetes-related QOL was significantly better
      in SPK recipients (1.8 +/- 0.5 versus 2.3 +/- 0.5; P < 0.05). SPK and KTA
      recipients' SF-36 physical (66 +/- 21 and 64 +/- 19) and mental (76 +/- 17 and 71
      +/- 22) composite scores were similar. QWB scores also were similar for SPK (0.67
      +/- 0.12) and KTA (0.63 +/- 0.10) recipients. In the first 3 months after
      transplantation, SPK recipients had a significantly higher number of hospital
      admissions per patient (1.9 +/- 0.9 versus 1.4 +/- 0.6; P < 0.05), more hospital
      days per patient (25.1 +/- 13.8 days versus 10.1 +/- 4.4 days; P < 0.005), and
      more intensive care unit days per patient (7.9 +/- 7.1 days versus 0.8 +/- 1.5
      days; P < 0.005). Although SPK transplantation enhanced diabetes-related QOL,
      there was no improvement in overall QOL.

PMID- 12046046
TI  - Hemodialysis-associated methemoglobinemia in acute renal failure.
AB  - Patients on maintenance hemodialysis are vulnerable to chloramine toxicity if
      chloramines are inadequately removed. We report two critically ill patients with
      acute renal failure who developed methemoglobinemia during hemodialysis in the
      intensive care unit. During the same period, methemoglobin levels measured from
      30 patients in the outpatient dialysis facility were undetectable. Methemoglobin
      levels normalized when the carbon filtration system of the portable dialysis
      machine was replaced with a larger unit to remove chloramines more effectively.
      Causes, treatment, and prevention of chloramine toxicity in patients receiving
      dialysis in the intensive care unit are discussed.

PMID- 12046047
TI  - Primary varicella after transplantation.
AB  - A 51-year-old white woman 6 months status post cadaveric renal transplant
      developed a mild case of primary varicella-zoster (VZ). It is hypothesized that
      the limited nature of her illness was due to infection with vaccine-type VZ virus
      instead of wild-type VZ. Approximately 1 month prior, she had daily household
      contact with a child who had developed a rash after immunization with live
      attenuated varicella vaccine. This case highlights several important questions.
      Should special precautions be undertaken with renal transplant recipients naive
      to varicella infection after vaccination of household contacts? Should
      pretransplant immunization with varicella vaccine be performed routinely in naive
      patients? Should naive patients transplanted and maintained on immunosuppressive
      therapy be vaccinated? Until there are clinical trials to answer these questions,
      it may be instructive to consider the recommendations for pediatric and
      immunocompromised patients.

PMID- 12046048
TI  - Celecoxib-induced acute interstitial nephritis.
AB  - Data about the nephrotoxicity of selective cyclooxygenase-2 inhibitors are still
      evolving. Acute interstitial nephritis is a well-described complication of
      therapy with nonselective nonsteroidal anti-inflammatory drugs. We report a case
      of biopsy-proven acute interstitial nephritis in a 73-year-old diabetic woman,
      who had taken celecoxib for more than 1 year before presentation. She presented
      with clinical findings of subnephrotic proteinuria and acute renal failure that
      required dialysis. She recovered renal function with cessation of celecoxib
      therapy after 2 weeks. Other medications were reintroduced safely, without
      recurrence of renal failure. A kidney biopsy specimen showed acute interstitial
      nephritis with a prominent eosinophilic infiltrate in the interstitium. This case
      documents the occurrence of acute interstitial nephritis with celecoxib and
      emphasizes the need for continued vigilance and care in use of cyclooxygenase-2
      inhibitors in high-risk patients.

PMID- 12046049
TI  - An opportune time to develop new strategies against repeat peritonitis in
      patients on peritoneal dialysis?

PMID- 12046050
TI  - Renal parenchymal injury as a determinant of clinical consequences in
      atherosclerotic renal artery stenosis.

PMID- 12046051
TI  - A 10-year-old girl with renal failure and granulomas.

PMID- 12046053
TI  - Primary cerebral lymphoma and membranous nephropathy: a still unreported
      association.
AB  - Paraneoplastic nephrotic syndrome (NS) in the setting of membranous nephropathy
      (MN) is a well-known and often prodromal complication of renal and extrarenal
      malignancy. Primary cerebral lymphoma is a rare neoplasm uncommonly investigated
      in the setting of NS. We describe for the first time a case of primary cerebral
      lymphoma in association with MN. An elderly woman presented for renal biopsy
      because an NS had been diagnosed previously and treated by steroid therapy.
      Primary membranous glomerulonephritis was diagnosed and immunosuppressive therapy
      was started. Twenty days later, she was readmitted because of left hemiplegia.
      Computed tomography and subsequent nuclear magnetic resonance evaluation of the
      brain documented an extensive cerebral space-occupying lesion. A cerebral
      malignant lymphoma was diagnosed at intraoperative histologic evaluation, and
      subsequent light microscopic and immunohistochemical studies allowed the
      diagnosis of peripheral T-cell lymphoma. Extensive clinical workup, including
      bone marrow biopsy, documented the lack of any neoplastic involvement outside the
      brain. Primary cerebral non-Hodgkin's lymphoma of peripheral T-cell derivation
      consequently was diagnosed. This case suggests that patients with MN,
      particularly elderly patients, should undergo complete screening for neoplasms.
      The absence of specific guidelines on this topic may be due partly to the lack of
      extensive description of all newly identified cases. All cases should be reported
      to evaluate whether this association is causal or fortuitous.

PMID- 12046054
TI  - Pheochromocytoma multisystem crisis in a patient with multiple endocrine
      neoplasia type IIB and pyelonephritis.
AB  - A patient with pyelonephritis developed multiorgan failure resulting in death.
      Clinical findings were consistent with multiple endocrine neoplasia type II, with
      bilateral pheochromocytomas identified by computed tomography scan. We
      hypothesize that either the infection or the administration of radiocontrast
      media led to a massive release of catecholamines from the pheochromocytomas. As a
      result, tissue perfusion was severely compromised, and multiorgan failure
      developed. This exceedingly rare complication of pheochromocytoma has been termed
      pheochromocytoma multisystem crisis.

PMID- 12046055
TI  - Infantile cystinosis presenting as chronic constipation.
AB  - An infant presented with persistent constipation as the first clinical symptom of
      cystinosis before evidence of renal Fanconi's syndrome. The history of muscle
      weakness, failure to thrive, polydipsia, and polyuria prompted subsequent
      clinical and laboratory evaluations, leading to the correct diagnosis of
      cystinosis. Primary and persistent constipation as an initial manifestation of
      cystinosis has not been reported previously. Although rare, cystinosis should be
      considered in the differential diagnosis of constipation if other suggestive
      signs or symptoms are present.

PMID- 12046057
TI  - Radiofrequence ablation of liver cancers.
AB  - Primary and secondary malignant liver cancer are some of most common malignant
      tumors in the world. Chemotherapy and radiotherapy are not very effective against
      them. Surgical resection has been considered the only potentially curtive option,
      but the majority of patients are not candidates for resection because of tumor
      size, location near major intrahepatic blood vessels and bile ducts, precluding a
      margin-negative resection, cirrhotic, hepatitis virus infection or multifocial.
      Radiofrequence ablation (RFA), which is a new evolving effective and minimally
      invasive technique, can produce coagulative necrosis of malignant tumors. RFA
      should be used percutaneously, laparascopically, or during the open laparotomy
      under the guidance of ultrasound, CT scan and MRI. RFA has lots of advantages
      superior to other local therapies including lower complications, reduced costs
      and hospital stays, and the possibility of repeated treatment. In general, RFA is
      a safe, effective treatment for unresectable malignant liver tumors less than 7.0
      cm in diameter. We review the principle, mechanism, procedures and experience
      with RFA for treating malignant liver tumors.

PMID- 12046056
TI  - The prognostic molecular markers in hepatocellular carcinoma.
AB  - The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although
      many advances in its clinical study have been made. It is important for tumor
      control to identify the factors that predispose patients to death. With new
      discoveries in cancer biology, the pathological and biological prognostic factors
      of HCC have been studied quite extensively. Analyzing molecular markers
      (biomarkers) with prognostic significance is a complementary method. A large
      number of molecular factors have been shown to associate with the invasiveness of
      HCC, and have potential prognostic significance. One important aspect is the
      analysis of molecular markers for the cellular malignancy phenotype. These
      include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67,
      Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its
      related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin
      E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms,
      HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas
      and FasL), as well as telomerase activity. Another important aspect is the
      analysis of molecular markers involved in the process of cancer invasion and
      metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular
      adhesion molecule-1, CD44 variants), proteinases involved in the degradation of
      extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules
      have been regarded as biomarkers for the malignant phenotype of HCC, and are
      related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to
      both the growth and metastasis of cancers including HCC, and has drawn much
      attention in recent years. Many angiogenesis-related markers, such as vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet
      derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP),
      angiogenin, pleiotrophin, and endostatin (ES) levels, as well as intratumor
      microvessel density (MVD) have been evaluated and found to be of prognostic
      significance. Body fluid (particularly blood and urinary) testing for biomarkers
      is easily accessible and useful in clinical patients. The prognostic significance
      of circulating DNA in plasma or serum, and its genetic alterations in HCC are
      other important trends. More attention should be paid to these two areas in
      future. As the progress of the human genome project advances, so does a clearer
      understanding of tumor biology, and more and more new prognostic markers with
      high sensitivity and specificity will be found and used in clinical assays.
      However, the combination of some items, i.e., the pathological features and some
      biomarkers mentioned above, seems to be more practical for now.

PMID- 12046058
TI  - Effects of histone acetylation and DNA methylation on p21( WAF1) regulation.
AB  - Cell cycle progression is regulated by interactions between cyclins and cyclin
      dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits
      CDKs activity. Increased expression of p21(WAF1) may play an important role in
      the growth arrest induced in transformed cells. Although the stability of the
      p21( WAF1) mRNA could be altered by different signals, cell differentiation and
      numerous influencing factors. However, recent studies suggest that two known
      mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region
      and changes to an inactive chromatin by histone deacetylation, seem to be the
      best candidate mechanisms for inactivation of p21( WAF1). To date, almost no
      coding region p21(WAF1) mutations have been found in tumor cells, despite
      extensive screening of hundreds of various tumors. Hypermethylation of the
      p21(WAF1) promoter region may represent an alternative mechanism by which the
      p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein
      levels also induces a corresponding rapid increase in the cell cycle regulator
      p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1)
      which is independent of methylation of DNA. Both histone hyperacetylation and
      hypoacetylation appear to be important in the carcinoma process, and induction of
      the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which
      dietary fiber prevents carcinogenesis. Here, we review the influence of histone
      acetylation and DNA methylation on p21(WAF1) transcription, and affection of
      pathways or factors associated such as p 53, E2A, Sp1 as well as several histone
      deacetylation inhibitors.

PMID- 12046060
TI  - Relationship between bilirubin free radical and formation of pigment gallstone.
AB  - In this paper, we summarize the main progresses made in our group in the field of
      the mechanism of pigment gallstone formation. It was found that after treatment
      with free radicals, bilirubin (BR) was changed into free radical itself, and a
      semiquinone free radical and a superoxide free radical bound with metal were
      recognized, which was detected by ESR (electron spin resonance). By the means of
      NMR (nuclear magnetic resonance) and IR (Infra-red spectra), it was postulated
      that bilirubin polymerized through the reaction between the vinyl group and the
      hydroxyl group under the attack of free radicals. It was also found that
      bilirubin free radical were liable to calcify in a kinetic study. Because of its
      chemical properties, bilirubin free radical was shown to be cytotoxic to
      hepatocyte, which was demonstrated based on the following facts: induction of
      phospholipid peroxidation (LPO), leakage of lactate dehydrogenase (LDH) and
      decrease of glutathione. As to the mechanism of bilirubin-induced cytotoxicity,
      it was postulated that the main target of bilirubin free radical was the cell
      membrane, including phospholipid and membrane bound proteins, especially
      spectrin, a content of cytoskeleton. Based on the results mentioned above, it was
      deduced that bilirubin free radical is the key factor that initiates and promotes
      the formation of pigment gallstone, which is consistent with other researches in
      recent years.

PMID- 12046061
TI  - Field population-based blocking treatment of esophageal epithelia dysplasia.
AB  - AIM: To confirm the value of blocking treatment by zenshengping (ZSP), a Chinese
      herb composite, and Riboflavin for esophageal epithelia dysplasia cases screened
      out in high risk area in northern china by exfoliative balloon cytology (EBC), so
      to reduce the incidence rate of esophageal cancer(EC). METHODS: Esophageal
      epithelium dysplasia cases including mind esophageal epithelium dysplasia (MEED),
      stage one severe esophageal epithelium dysplasia (SEED I), and stage two severe
      esophageal epithelium dysplasia (SEED II) were screened out from people aged 40
      years and older in the high risk area of Chixian. These cases were randomly
      divided into a treatment and control group. Subjects in the treatment and control
      groups took ZSP, riboflavin, and placebo daily for three years. EC cases
      registered by cancer registry and identified by EBC re-screening in the treatment
      and control groups were used to calculate incidence and blocking rates to
      demonstrate the effects of blocking medication. RESULTS: It was found that 31.92%
      and 24.15% of people aged 40 years and older in Cixian could been diagnosed as
      MEED and SEED cases. The severity of dysplasia increased with age. ZSP had
      blocked EC occurrence by 47.79% after 3 year medication among the SEED cases.
      CONCLUSION: ZSP can block the development from SEED I and SEED II to EC by
      47.79%. Efforts should be made to screen and treat dysplasia cases in people aged
      40 years and older in high risk areas to reduce the mortality figures.

PMID- 12046062
TI  - Tumor suppressor gene p16 and Rb expression in gastric cardia precancerous
      lesions from subjects at a high incidence area in northern China.
AB  - AIM: To further understand the molecular basis for gastric cardia carcinogenesis
      and to provide etiological clues. METHODS: Endoscopic mucosa biopsy and
      histopathological examinations were made on 37 subjects from a high incidence
      area for both esophageal and gastric cardia carcinomas in northern China. All the
      biopsy samples were fixed in 850 ml. (-1)L alcohol and embedded in paraffin. Each
      block contained one piece of tissue and was serially section at 5 microm.
      Immunohistochemistry (ABC) was carried out on these gastric cardia samples to
      determine the alterations of p16 and Rb. RESULTS: Based on the histopathlogical
      examination there were 11 cases of chronic superficial gastritis, 12 cases of
      chronic atrophic gastritis and 14 cases of dysplasia. The immunostaining
      demonstrated different levels of unclear immunostaining of p16 and Rb in normal
      gastric cardia tissue and the tissues with different severity of lesions. With
      the lesions progressing, the positive immunostaining rates for p16 protein had a
      decreasing tendency. In contrast, the positive immunostaining rate for Rb protein
      had an increasing tendency. There was a significant negative relationship between
      the two parameters. Changes of p16 was CSG 11(100%), CAG 7(58%), DYS 4(29%) and
      changes of Rb was CSG 2(18%), CAG 8(67%) and DYS 12(86%), (P<0.05). CONCLUSION:
      The alterations of p16 and Rb protein may play a role in the early stages of
      gastric cardia carcinogenesis.

PMID- 12046063
TI  - Rapid screening mitochondrial DNA mutation by using denaturing high-performance
      liquid chromatography.
AB  - AIM: To optimize conditions of DHPLC and analyze the effectiveness of various DNA
      polymerases on DHPLC resolution, and evaluate the sensitivity of DHPLC in the
      mutation screening of mitochondrial DNA (mtDNA). METHODS: Two fragments of 16s
      gene of mitochondrial DNA (one of them F2 is a mutant fragment) and an A3243G
      mutated fragment were used to analyze the UV detection limit and determine the
      minimum percentage of mutant PCR products for DHPLC and evaluate effects of DNA
      polymerases on resolution of DHPLC. Under the optimal conditions, we analyzed the
      mtDNA mutations from muscle tissues of mitochondrial encephalomyopathy with
      lactic acidosis and stroke-like episodes (MELAS) and screened blindly for
      variances in D-loop region of mtDNA from human gastric tumor specimen. RESULTS:
      Ten A3243G variants were detected in 12 cases of MELAS, no alterations were
      detected in controls and these results were consistent with the results obtained
      by analysis of RFLP with ApaI. We also identified 26 D-loop variances in 46 cases
      of human gastric cancer tissues and 38 alterations in 13 gastric cancer cell
      lines. The mutation of mtDNA at 80 ng PCR products containing a minimum of 5%
      mutant sequences could be detected by using DHPLC with UV detector. Moreover,
      Ampli-Taq Gold polymerase was equally as good as the proofreading DNA polymerase
      (e.g., Pfu) in eliminating the false positive produced by Taq DNA polymerases.
      CONCLUSION: DHPLC is a powerful, rapid and sensitive mutation screening method
      for mtDNA. Proofreading DNA polymerase is more suitable for DHPLC analysis than
      Taq polymerase.

PMID- 12046059
TI  - Influencing factors of pancreatic microcirculatory impairment in acute
      panceatitis.
AB  - Pancreatic microcirculatory disturbance plays an important role in th e
      pathogenesis of acute pancreatitis, and it involves a series of changes including
      vasoconstriction, ischaemia, increased vascular permeability, impairment of
      nutritive tissue perfusion, ischaemia/reperfusion, leukocyte adherence,
      hemorrheological changes and impaired lymphatic drainage. Ischaemia possibly acts
      as an initiating factor of pancreatic microcirculatory injury in acute
      pancreatitis, or as an aggravating/continuing mechanism. The end-artery feature
      of the intralobular arterioles suggests that the pancreatic microcirculation is
      highly susceptible to ischaemia. Various vasoactive mediators, as bradykinin,
      platelet activating factor, endothelin and nitric oxide participate in the
      development of microcirculatory failure.

PMID- 12046065
TI  - Inhibition of human telomerase in MKN-45 cell line by antisense hTR expression
      vector induces cell apoptosis and growth arrest.
AB  - AIM: To investigate the effects of antisense human telomerase RNA (hTR)on the
      biologic behavior of human gastric cancer cell line: MKN-45 by gene transfection
      and its potential role in the gene therapy of gastric cancer. METHODS: The hTR
      cDNA fragment was cloned from MKN-45 through RT-PCR and subcloned into eukaryotic
      expression vector (pEF6/V5-His-TOPO) in cis-direction or trans-direction by DNA
      recombinant methods. The constructed sense, antisense and empty vectors were
      transfected into MKN-45 cell lines separately by lipofectin-mediated DNA
      transfection technology. After drug selection, the expression of antisense hTR
      gene in stable transfectants and normal MKN-45 cells was detected by RT-PCR, the
      telomerase activity by TRAP, the apoptotic features by PI and Hoechst 33258
      staining, the cell cycle distribution by flow cytometry and the population
      doubling time by cell counting. Comparison among the stable transfectants and
      normal MKN-45 cells was made. RESULTS: The sense, antisense hTR eukaryotic
      expression vectors and empty vector were successfully constructed and proved to
      be the same as original design by restriction endonuclease analysis and
      sequencing. Then, they were successfully transfected into MKN-45 cell lines
      separately with lipofectin. The expression of antisense hTR gene was only
      detected in MKN-45 cells stably transfected with antisense hTR vector (named as
      MKN-45-ahTR) but not in the control cells. In MKN-45-ahTR, the telomerase
      activity was inhibited by 75%, the apoptotic rate was increased to 25.3%, the
      percentage of cells in the G0/G1 phase was increased to 65%, the proliferation
      index was decreased to 35% and the population doubling time was prolonged to 35.3
      hours. However, the telomerase activity, the apoptotic rate, the distribution of
      cell cycle, the proliferation index and the population doubling time were not
      different among the control cells. CONCLUSION: Antisense hTR can significantly
      inhibit telomerase activity and proliferation of MKN-45 cells and induce cell
      apoptosis. Antisense gene therapy based on telomerase inhibition can be a
      potential therapeutic approach to the treatment of gastric cancer.

PMID- 12046064
TI  - Changes of NF-kB, p53, Bcl-2 and caspase in apoptosis induced by JTE-522 in human
      gastric adenocarcinoma cell line AGS cells: role of reactive oxygen species.
AB  - AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also
      involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and
      caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy,
      agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility
      shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on
      cell proliferation and apoptosis in AGS cells and related molecular mechanisms.
      RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis.
      Lucigenin assay showed the generation of ROS in cells under incubation with JTE
      522. The increased ROS generation might contribute to the induction of AGS cells
      to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost
      completely inhibited by preventing the degradation of IkBalpha. Additionally, by
      using Western blot we confirmed that the level of bcl-2 was decreased, whereas
      p53 showed a great increase following JTE-522 treatment. Their changes were in a
      dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen
      species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the
      induction of apoptosis in AGS cells after treatment with JTE-522.

PMID- 12046066
TI  - Expression and function of classical protein kinase C isoenzymes in gastric
      cancer cell line and its drug-resistant sublines.
AB  - AIM: To investigate the expression and function of classical protein kinase C
      (PKC) isoenzymes in inducing MDR phenotype in gastric cancer cells. METHODS: Two
      cell lines were used in the study: gastric cancer cell SGC7901 and its drug
      resistant cell SGC7901/VCR stepwise-selected by vincristine 0.3, 0.7 and 1.0
      mg.L(-1), respectively. The expression of classical PKC (cPKC) isoenzymes in
      SGC7901 cells and SGC7901/VCR cells were detected using immunofluorescent
      cytochemistry, laser confocal scanning microscope and Western blot. The effects
      of anti-PKC isoenzymes antibody on adriamycin accumulation in SGC7901/VCR cells
      were determined using flow cytometric analysis. RESULTS: (1)SGC7901 cells
      exhibited positive staining of PKC-alpha. SGC7901/VCR cells exhibited stronger
      staining of PKC-alpha than SGC7901 cells. The higher dosage vincristine selected,
      the much stronger staining of PKC-alpha was observed on SGC7901/VCR cells.
      (2)Both SGC7901 and SGC7901/VCR cells exhibited positive staining of PKC-beta I
      and PKC-beta II with no significant difference. (3) Compared with SGC7901,
      SGC7901/VCR cells had decreased adriamycin accumulation and retention.
      Accumulation of adriamycin in SGC7901 was 5.21+/-2.56 mg.L(-1),in SGC7901/VCR 0.3
      was 0.85+/-0.29 mg.L(-1), in SGC7901/VCR 0.7 was 0.81+/-0.32 mg.L(-1), and in
      SGC7901/VCR 1.0 was 0.80+/-0.33 mg.L(-1); Retention of adriamycin in SGC 7901 was
      2.51+/-1.23 mg.L(-1), in SGC7901/VCR 0.3 was 0.47+/-0.14 mg.L(-1), in SGC7901/VCR
      0.7 was 0.44+/-0.15 mg.L(-1), and in SGC 7901/VCR 1.0 was 0.41+/-0.11 mg.L(-1).
      (4) Fluorescence intensity presented adriamycin accumulation in SGC7901/VCR cells
      was increased from 1.14+/-0.36 to 2.71+/-0.94 when cells were co-incubated with
      anti-PKC-alpha but not with anti-PKC-beta I PKC-beta II and PKCgamma antibodies.
      CONCLUSION: PKC-alpha, but not PKC-beta I, PKC-beta II or PKCgamma, may play a
      role in multidrug resistance of gastric cancer cells SGC7901/VCR.

PMID- 12046067
TI  - Induction of apoptosis by TPA and VP-16 is through translocation of TR3.
AB  - AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer
      cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of
      TR3 mRNA and its protein was detected by Northern blot and Western blot.
      Localization of TR3 protein was showed by immunofluorescence analysis under laser
      scanning confocal microscope. Apoptotic morphology was observed by DAPI
      fluorescence staining, and apoptotic index was counted among 1000 cells randomly.
      Stable transfection assay was carried out by Lipofectamine. RESULTS: Treatment of
      MGC80-3 cells with TPA and VP-16 resulted in apoptosis, accompanied by the
      repression of Bcl-2 protein in a time-dependent manner. At the same time, TPA and
      VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that
      expressed TR3 mRNA. When antisense-TR3 expression vector was transfected into the
      cells, expression of TR3 protein was repressed. In this case, TPA and VP-16 did
      not induce apoptosis. In addition, TPA and VP-16-induced apoptosis involved in
      translocation of TR3. In MGC80-3 cells, TR3 localized concentrative in nucleus,
      after treatment of cells with TPA and VP-16, TR3 translocated from nucleus to
      cytosol obviously. However, when this nuclear translocation was blocked by LMB,
      apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP
      16. CONCLUSION: Induction of apoptosis by TPA and VP-16 is through induction of
      TR3 expression and translocation of TR3 from nucleus to cytosol, which may be a
      novel signal pathway for TR3, and represent the new biological function of TR3 to
      exert its effect on apoptosis in gastric cancer cells.

PMID- 12046068
TI  - Effect of preoperative regional artery chemotherapy on proliferation and
      apoptosis of gastric carcinoma cells.
AB  - AIM: To study the effects of preoperative regional artery chemotherapy (PRACT) in
      inducing growth inhibition and apoptosis of gastric carcinoma (GC) cells.
      METHODS: TUNEL (terminal-deoxynucleotidyl-transferase TdT-mediated dUTP
      fluorescein and labeling) method and immunohistochemical techniques were used to
      detect the state of apoptosis and proliferation of GC cells in histopathologic
      sections. A total of 110 cases of GC and 68 cases of metastatic lymph node with
      or without PRACT were adopted. Correlations between apoptosis index (AI),
      proliferation index (PI) and PRACT and prognosis were analysed. RESULTS: The
      apoptosis index (AI) was significantly higher in the PRACT group (12.5 +/-4.33 )
      than in the untreated group (7.1 +/-3.43 , P<0.001), whereas the proliferation
      index (PI) in the PRACT group (33.8%+/-8.8%) was significantly lower than that in
      untreated group (43.6%+/-12.8%, P<0.01). Both AI and PI were correlated to the
      differentiation degree of GC in PRACT group, the AI in the differentiated group
      was higher than that in undifferentiated group (P<0.001), but the PI was lower in
      the differentiated group than that of the undifferentiated group (P<0.01). The AI
      of GC cells in metastatic lymph node was also significantly higher in the PRACT
      group (7.9 +/-3.41 ) than in the untreated group (3.6 +/-2.93 , P<0.01), though
      the PI of GC cells in metastatic lymph nodes in the PRACT group (17.2%+/-6.8%)
      was significantly lower than that in the untreated group (26.7%+/-9.3%, P<0.01).
      The severity of histopathologic changes was significantly higher in the PRACT
      group than in the untreated group (P<0.05). In addition, postoperative surveys
      demonstrated that the 5-year survival rate of GC patients in the PRACT group was
      significantly higher than that of patients in the untreated group (P<0.01).
      CONCLUSION: Preoperative regional artery chemotherapy (PRACT) showed inhibitory
      action on the growth of GC cells mainly through inhibiting proliferation and
      inducing the apoptosis of tumor cells. PRACT can improve the progno sis of GC
      patients also.

PMID- 12046069
TI  - Effects of epidermal growth factor on the growth of human gastric cancer cell and
      the implanted tumor of nude mice.
AB  - AIM: Epidermal growth factor (EGF) plays an important role in the regulation of
      gastrointestinal tissue growth and development, and it can stimulate epithelial
      proliferation, cell differentiation and growth. It has been established that the
      EGF can promote gastric cytoprotection and ulcer healing. But the potential
      ability of EGF to regulate the gastric cancer growth is unknown. This study is to
      investigate the influence of EGF on human gastric cancer cell and the implanted
      tumor growth of nude mice. METHODS: The cell growth rates of human gastric
      adenocarcinoma cell lines MKN-28, MKN-45, SGC-7901 and normal human gastric
      epithelial cells 3T3 were assessed when incubated with recombinant human EGF
      (rhEGF, 0.05, 0.1, 0.5, 1.0, 10, 50, 100 mg.L(-1)) using MTT method. The cells of
      MKN-28, MKN-45, SGC-7901 (gastric cancer tissue 1.5mm(3)) were implanted in the
      BALB/cA nude mice for 10 days. The EGF was given intraperitoneally (15, 30, 60
      microg.kg(-1)) for 3 weeks. The body weights of the tumor-bearing animals and
      their tumor mass were measured afterwards to assess the mitogenic effect of rhEGF
      in the nude mice. RESULTS: Within the concentration range of 0.05-100mg.L(-1),
      rhEGF could increase the cell growth of normal 3T3 cells (cell growth rate 100%
      vs 102.8%, P<0.05), but partially restrain the gastric cancer cell growth. The
      latter effect was related to cell differentiation. In 15-60 microg/kg rhEGF
      groups, the mean implanted tumor mass of MKN-28 cell were 1.75 g, 1.91 g, 2.08
      g/NS group 1.97 g (P>0.05), the mean tumor mass of SGC-7901 cell were 1.53 g,
      1.07 g, 1.20 g/NS group 1.07 g (P>0.05), and for MKN-45 cell, the tumor mass were
      respectively 1.92 g, 1.29 g, 1.77 /NS group 1.82 g (P>0.05). So rhEGF had no
      obvious effect on implanted MKN-28, SGC-7901 and MKN-45 tumor growth. CONCLUSION:
      EGF has no stimulating effect on the human gastric cancer cell growth neither in
      vitro nor in vivo.

PMID- 12046070
TI  - P53 immunohistochemical scoring: an independent prognostic marker for patients
      after hepatocellular carcinoma resection.
AB  - AIM: To confirm if p53 mutation could be a routine predictive marker for the
      prognosis of hepatocellular carcinoma (HCC) patients. METHODS: Two hundreds and
      forty-four formalin-fixed paraffin-embedded tumor samples of the patients with
      HCC receiving liver resection were detected for nuclear accumulation of p53. The
      percent of P53 immunoreactive tumor cells was scored as 0 to 3+ in P53 positive
      region (<10% -, 10-30% +, 31-50% ++, >50% +++). Proliferating cell nuclear
      antigen (PCNA) and some clinicopathological characteristics, including patients'
      sex, preoperative serum AFP level, tumor size, capsule, vascular invasion (both
      visual and microscopic), and Edmondson grade were also evaluated. RESULTS: In
      univariate COX harzard regression model analysis, tumor size, capsule status,
      vascular invasion, and p53 expression were independent factors that were closely
      related to the overall survival (OS) rates of HCC patients. The survival rates of
      patients with 3+ for P53 expression were much lower than those with 2+ or + for
      P53 expression. Only vascular invasion (P<0.05) and capsule (P<0.01) were closely
      related to the disease-free survival (DFS) of HCC patients. In multivariate
      analysis, p53 overexpression (RI 0.5456, P<0.01) was the most significant factor
      associated with the OS rates of patients after HCC resection, while tumor size
      (RI 0.5209, P<0.01), vascular invasion (RI 0.5271, P<0.01) and capsule (RI
      0.8691, P<0.01) were also related to the OS. However, only tumor capsular status
      was an independent predictive factor (P<0.05) for the DFS. No significant
      prognostic value was found in PCNA-LI, Edmondson's grade, patients' sex and
      preoperative serum AFP level. CONCLUSION: Accumulation of p53 expression, as well
      as tumor size, capsule and vascular invasion, could be valuable markers for
      predicting the prognosis of HCC patients after resection. The quantitative
      immunohistochemical scoring for P53 nuclear accumulation might be more valuable
      for predicting prognosis of patients after HCC resection than the common
      qualitative analysis.

PMID- 12046071
TI  - Antitumor activities of human autologous cytokine-induced killer (CIK) cells
      against hepatocellular carcinoma cells in vitro and in vivo.
AB  - AIM: To characterize the anticancer function of cytokine-induced killer cells
      (CIK) and develop an adoptive immunotherapy for the patients with primary
      hepatocellular carcinoma (HCC), we evaluated the proliferation rate, phenotype
      and the antitumor activity of human CIK cells from healthy donors and HCC
      patients in vitro and in vivo. METHODS: Peripheral blood mononuclear cells (PBMC)
      from healthy donors and patients with primary HCC were incubated in vitro and
      induced into CIK cells in the presence of various cytokines such as interferon
      gamma (IFN-gamma), interleukin-1 (IL-1), IL-2 and monoclonal antibody (mAb)
      against CD3. The phenotype and characterization of CIK cells were identified by
      flow cytometric analysis. The cytotoxicity of CIK cells was determined by (51)Cr
      release assay. RESULTS: The CIK cells were shown to be a heterogeneous population
      with different cellular phenotypes. The percentage of CD3+/CD56+ positive cells,
      the dominant effector cells, in total CIK cells from healthy donors and HCC
      patients, significantly increased from 0.1-0.13% at day 0 to 19.0-20.5% at day 21
      incubation, which suggested that the CD3+ CD56+ positive cells proliferated
      faster than other cell populations of CIK cells in the protocol used in this
      study. After 28 day in vitro incubation, the CIK cells from patients with HCC and
      healthy donors increased by more than 300-fold and 500-fold in proliferation cell
      number, respectively. CIK cells originated from HCC patients possessed a higher
      in vitro antitumor cytotoxic activity on autologous HCC cells than the autologous
      lymphokine-activated killer (LAK) cells and PBMC cells. In in vivo animal
      experiment, CIK cells had stronger effects on the inhibition of tumor growth in
      Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory
      rate, 84.7% vs 52.8%, P<0.05) or PBMC (mean inhibitory rate, 84.7% vs 37.1%,
      P<0.01). CONCLUSION: Autologous CIK cells are of highly efficient cytotoxic
      effector cells against primary hepatocellular carcinoma cells and might serve as
      an alternative adoptive therapeutic strategy for HCC patients.

PMID- 12046072
TI  - The promoting molecular mechanism of alpha-fetoprotein on the growth of human
      hepatoma Bel7402 cell line.
AB  - AIM: The goal of this study was to characterize the AFP receptor, its possible
      signal transduction pathway and its proliferative functions in human hepatoma
      cell line Bel 7402. METHODS: Cell proliferation enhanced by AFP was detected by
      MTT assay, 3H-thymidine incorporation and S-stage percentage of cell cycle
      analysis. With radioactive labeled 125I-AFP for receptor binding assay; cAMP
      accumulation, protein kinase A activity were detected by radioactive
      immunosorbent assay and the change of intracellular free calcium (Ca2+i) was
      monitored by scanning fluorescence intensity under TCS-NT confocal microscope.
      The expression of oncogenes N- ras, p 53, and p21( ras ) in the cultured cells in
      vitro were detected by Northern blotting and Western blotting respectively.
      RESULTS: It was demonstrated that AFP enhanced the proliferation of human
      hepatoma Bel 7402 cell in a dose dependent fashion as shown in MTT assay, (3)H
      thymidine incorporation and S-phase percentage up to 2-fold. Two subtypes of AFP
      receptors were identified in the cells with Kds of 1.3 x 10(-9)mol.L(-1) and 9.9
      x10(-8)mol. (-1)L respectively. Pretreatment of cells with AFP resulted in a
      significant increase (625%) in cAMP accumulation. The activity of protein kinase
      A activity were increased up to 37.5, 122.6, 73.7 and 61.2% at treatment time
      point 2, 6, 12 and 24 hours. The level of intracellular calcium were elevated
      after the treatment of alpha-fetoprotein and achieved to 204% at 4 min. The
      results also showed that AFP(20mg.L(-1)) could upregulate the expression of N-
      ras oncogenes and p 53 and p21( ras ) in Bel 7402 cells. In the later case,the
      alteration were 81.1%(12h) and 97.3%(12h) respectively compared with control.
      CONCLUSION: These results demonstrate that AFP is a potential growth factor to
      promote the proliferation of human hepatoma Bel 7402 cells. Its growth-regulatory
      effects are mediated by its specific plasma membrane receptors coupled with its
      transmembrane signaling transduction through the pathway of cAMP-PKA and
      intracellular calcium to regulate the expression of oncogenes.

PMID- 12046074
TI  - The point mutation of p53 gene exon7 in hepatocellular carcinoma from Anhui
      Province, a non HCC prevalent area in China.
AB  - AIM: In hepatocellular carcinoma (HCC) prevalent areas of China, the point
      mutation of p53 exon7 is highly correlated with Hepatitis B virus(HBV) infection
      and aflatoxin B intake. While in non-HCC-prevalent areas of China, these factors
      are not so important in the etiology of HCC. Therefore, the point mutation of p53
      exon7 may also be different than that in HCC-prevalent areas of China. The aim of
      this study is to investigate the status and carcinogenic role of the point
      mutation of p53 gene exon7 in hepatocellular carcinoma from Anhui Province, a non
      HCC-prevalent area in China. METHODS: PCR PCR-SSCP and PCR-RFLP were applied to
      analyze the homozygous deletion and point mutation of p53 exon7 in HCC samples
      from Anhui, which were confirmed by DNA sequencing and Genbank comparison.
      RESULTS: In the 38 samples of hepatocellular carcinoma, no homozygous deletion of
      p53 exon7 was detected and point mutations of p53 exon7 were found in 4 cases,
      which were found to be heterozygous mutation of codon 249 with a mutation rate of
      10.53%(4/38). The third base mutation(G-T) of p53 codon 249 was found by DNA
      sequencing and Genbank comparison. CONCLUSION: The incidence of point mutation of
      p53 codon 249 is lower in hepatocellular carcinoma and the heterozygous mutation
      of p53 exon7 found in these patients only indicate that they have genetic
      susceptibility to HCC. p53 codon 249 is a hotspot of p53 exon7 point mutation,
      suggesting that the point mutation of p53 exon 7 may not play a major role in the
      carcinogenesis of HCC in Anhui Province, a non-HCC-prevalent area in China.

PMID- 12046073
TI  - Influence of hepatic arterial blockage on blood perfusion and VEGF, MMP-1
      expression of implanted liver cancer in rats.
AB  - AIM: To investigate the influence of hepatic arterial blockage on blood perfusion
      of transplanted cancer in rat liver and the expression of vascular endothelial
      growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the
      mechanisms involved in transarterial embolization (TAE)-induced metastasis of
      liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted
      into rat liver to establish the liver cancer model. Hepatic arterial ligation
      (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood
      perfusion of tumor in control, laparotomy control, and HAL group was analyzed by
      Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the
      expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS:
      Two days after HAL, the number of Hoechst 33342 labeled cells which represent the
      blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group
      decreased significantly compared with that in control group (329+/-29 vs 384+/
      19, P<0.01). The serum VEGF level in the HAL group increased significantly as
      against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19
      ng.L(-1), P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of
      the HAL group increased significantly compared with that of the control and the
      laparotomy control groups (P<0.05). The blood perfusion data of the tumor,
      represented by the number of Hoechst 33342 labeled cells, showed a good linear
      inverse correlation with the serum VEGF level (r=-0.606, P<0.05) and the
      expression of VEGF mRNA in the tumor tissue ( r =-0.338, P<0.01). CONCLUSION:
      Blockage of hepatic arterial blood supply results in decreased blood perfusion
      and increased expression of metastasis-associated genes VEGF and MMP-1 of
      transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be
      the major cause of up-regulated expression of VEGF.

PMID- 12046075
TI  - Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721
      cells.
AB  - AIM: Cyclooxygenase-2 (COX-2) has been suggested to be associated with
      carcinogenesis. We sought to investigate the effect of the selective COX-2
      inhibitor, Nimesulide on proliferation and apoptosis of SMMC-7721 human hepatoma
      cells. METHODS: This study was carried out on the culture of hepatic carcinoma
      SMMC-7721 cell line. Various concentrations of Nimesulide (0, 200 micromol/L, 300
      micromol/L, 400 micromol/L) were added and incubated. Cell proliferation was
      detected with MTT colorimetric assay, cell apoptosis by electron microscopy, flow
      cytometry and TUNEL. RESULTS: Nimesulide could significantly inhibit SMMC-7721
      cells proliferation dose-dependent and in a dependent manner compared with that
      of the control group. The duration lowest inhibition rate produced by Nimesulide
      in SMMC-7721 cells was 19.06%, the highest inhibition rate was 58.49%. After
      incubation with Nimesulide for 72 h, the most highest apoptosis rate and
      apoptosis index of SMMC-7721 cells comparing with those of the control were
      21.20%+/-1.62% vs 2.24%+/-0.26% and 21.23+/-1.78 vs 2.01+/-0.23 (P<0.05).
      CONCLUSION: The selective COX-2 inhibitor, Nimesulide can inhibit the
      proliferation of SMMC-7721 cells and increase apoptosis rate and apoptosis index
      of SMMC-7721 cells. The apoptosis rate and the apoptosis index are dose
      dependent. Under electron microscope SMMC-7721 cells incubated with 300 micromol
      and 400 micromol Nimesulide show apoptotic characteristics. With the
      clarification of the mechanism of selective COX-2 inhibitors, These COX-2
      selective inhibitors can become the choice of prevention and treatment of
      cancers.

PMID- 12046076
TI  - Reduction of the incidence and mortality of rectal cancer by polypectomy: a
      prospective cohort study in Haining County.
AB  - AIM: To reduce the incidence and mortality of rectal cancer and address the
      hypothesis that colorectal cancer often arise from precursor lesion(s), either
      adenomas or non-adenomatous polyps, by conducting a population-based mass
      screening for colorectal cancer in Haining County, Zhejiang, PRC. METHODS: From
      1977 to 1980, physicians screened the population of Haining County using 15 cm
      rigid endoscopy. Of over 240000 participants, 4076 of them were diagnosed with
      precursor lesions, either adenomas or non-adenomatous polyps, which were then
      removed surgically. All individuals with precursor lesions were followed up and
      reexamined by endoscopy every two to five years up to 1998. RESULTS: After the
      initial screening, 953 metachronous adenomas and 417 non-adenomatous polyps were
      detected and removed from the members of this cohort. Further, 27 cases of
      colorectal cancer were detected and treated. Log-rank tests showed that the
      survival time among those cancer patients who under went mass screening increased
      significantly compared to that of other colorectal cancer patients (P<0.0001).
      According to the population-based cancer registry in Haining County, age-adjusted
      incidence and mortality of rectal cancer decreased by 41% and 29% from 1977-1981
      to 1992-1996, respectively. Observed cumulative 20-year rectal cancer incidence
      was 31% lower than the expected in the screened group; the mortality due to
      rectal cancer was 18% lower than the expected in the screened group. CONCLUSION:
      Mass screening for rectal cancer and precursor lesions with protocoscopy in the
      general population and periodical following-up with routine endoscopy for high
      risk patients may decrease both the incidence and mortality of rectal cancer.

PMID- 12046077
TI  - Effects of ursolic acid and oleanolic acid on human colon carcinoma cell line
      HCT15.
AB  - AIM: Ursolic acid (UA) and oleanolic acid (OA) are triperpene acids having a
      similar chemical structure and are distributed wildly in plants all over the
      world. In recent years, it was found that they had marked anti-tumor effects.
      There is little literature currently available regarding their effects on colon
      carcinoma cells. The present study was designed to investigate their inhibitory
      effects on human colon carcinoma cell line HCT15. METHODS: HCT15 cells were
      cultured with different drugs. The treated cells were stained with hematoxylin
      eosin and their morphologic changes observed under a light microscope. The
      cytotoxicity of these drugs was evaluated by tetrazolium dye assay. Cell cycle
      analysis was performed by flow cytometry (FCM). Data were expressed as means +/
      SEM and Analysis of variance and Student' t-test for individual comparisons.
      RESULTS: Twenty-four to 72 h after UA or OA 60 micromol/L treatment, the numbers
      of dead cells and cell fragments were increased and most cells were dead at the
      72nd hour. The cytotoxicity of UA was stronger than that of OA. Seventy-eight
      hours after 30 micromol/L of UA or OA treatment, a number of cells were
      degenerated, but cell fragments were rarely seen. The IC(50) values for UA and OA
      were 30 and 60 micromol/L, respectively. Proliferation assay showed that
      proliferation of UA and OA-treated cells was slightly increased at 24h and
      significantly decreased at 48 h and 60 h, whereas untreated control cells
      maintained an exponential growth curve. Cell cycle analysis by FCM showed HCT15
      cells treated with UA 30 and OA 60 for 36 h and 72 h gradually accumulated in
      G(0)/G(1) phase (both drugs P<0.05 for 72 h), with a concomitant decrease of cell
      populations in S phase (both drugs P<0.01 for 72 h) and no detectable apoptotic
      fraction. CONCLUSION: UA and OA have significant anti-tumor activity. The effect
      of UA is stronger than that of OA. The possible mechanism of action is that both
      drugs have an inhibitory effect on tumor cell proliferation through cell-cycle
      arrest.

PMID- 12046078
TI  - TGF beta1 expression and angiogenesis in colorectal cancer tissue.
AB  - AIM: Transforming growth factor TGF beta1 is involved in a variety of important
      cellular functions,including cell growth and differentiation, angiogenesis,
      immune function and extracellular matrix formation. However, the role of TGF
      beta(1) as an angiogenic factor in colorectal cancer is still unclear. We
      investigate the relationship between transforming growth factor beta(1) and
      angiogenesis by analyzing the expression of transforming growth factor TGF
      beta(1) in colorectal cancer, as well as its association with VEGF and MVD.
      METHODS: The expression of TGF beta(1),VEGF, as well as MVD were detected in 98
      colorectal cancer by immunohistochemical staining. The relationship between the
      TGF beta(1) expression and VEGF expression,MVD was evaluated. To evaluate the
      effect of TGF beta(1) on the angiogenesis of colorectal cancers. RESULTS: Among
      98 cases of colorectal cancer,37 were positive for TGF beta(1) 37.8% 36 for VEGF
      36.7% respectively. The microvessel counts ranged from 19 to 139.8, with a mean
      of 48.7(standard deviation,21.8). The expression of TGF beta(1) was correlated
      significantly with the depth of invasion, stage of disease, lymph node
      metastasis, VEGF expression and MVD. Patients in T3-T4, stage III-IV and with
      lymph node metastasis had much higher expression of TGF beta(1) than patients in
      T1-T2, stage I-II and without lymph node metastasis (P<0.05). The positive
      expression rate of VEGF(58.3%) in the TGF-beta(1) positive group is higher than
      that in the TGF-beta(1) negative group(41.7%, P<0.05). Also, the microvessel
      count (54+/-18) in TGF-beta(1) positive group is significantly higher than that
      in TGF-beta(1) negative group(46+/-15, P<0.05). The microvessel count in tumors
      with both TGF-beta(1) and VEGF positive were the highest (58+/-20 36-140,
      P<0.05). Whereas that in tumors with both TGF-beta(1) and VEGF negative were the
      lowest (38+/-16, 19-60, P<0.05). CONCLUSION: TGF beta(1) might be associated with
      tumor progression by modulating the angiogenesis in colorectal cancer and TGF
      beta(1) may be used as a possible biomarker.

PMID- 12046079
TI  - Full-length core sequence dependent complex-type glycosylation of hepatitis C
      virus E2 glycoprotein.
AB  - AIM: To study HCV polyprotein processing is important for the understanding of
      the natural history of HCV and the design of vaccines against HCV. The purpose of
      this study is to investigate the affection of context sequences on hepatitis C
      virus (HCV) E2 processing. METHODS: HCV genes of different lengths were expressed
      and compared in vaccinia virus/T7 system with homologous patient serum S94 and
      mouse anti-serum M( E2116) raised against E.coli -derived E2 peptide,
      respectively. Deglycosylation analysis and GNA ( Galanthus nivalus ) lectin
      binding assay were performed to study the post-translational processing of the
      expressed products. RESULTS: E2 glycoproteins with different molecular weights (
      75 kDa and -60 kDa) were detected using S94 and M( E2116), respectively.
      Deglycosylation analysis showed that this difference was mainly due to different
      glycosylation. Endo H resistance and its failure to bind to GNA lectin
      demonstrated that the higher molecular weight form (75 kDa) of E2 was complex
      type glycosylated, which was readily recognized by homologous patient serum S94.
      Expression of complex-type glycosylated E2 could not be detected in all of the
      core-truncated constructs tested, but readily detected in constructs encoding
      full-length core sequences. CONCLUSION: The upstream conserved full-length core
      coding sequence was required for the production of E2 glycoproteins carrying
      complex-type N-glycans which reacted strongly with homologous patient serum and
      therefore possibly represented more mature forms of E2. As complex-type N-glycans
      indicated modification by Golgi enzymes, the results suggest that the presence of
      full-length core might be critical for E1/E2 complex to leave ER. Our data may
      contribute to a better understanding of the processing of HCV structural proteins
      as well as HCV morphogenesis.

PMID- 12046081
TI  - Effects of Yigan Decoction on proliferation and apoptosis of hepatic stellate
      cells.
AB  - AIM: To investigate the effects of Chinese herb Yigan Decoction on proliferation
      and apoptosis of the hepatic stellate cells (HSC) in vitro. METHODS: The study in
      vitro was carried out in the culture of HSC lines. Various concentrations of
      Yigan Decoction were added and incubated. Cell proliferation was detected with
      MTT colorimetric assay. Cell apoptosis was detected by electron microscopy, flow
      cytometry and TUNEL. RESULTS: The proliferation of HSC was inhibited by Yigan
      Decoction, which depending on dose and time significantly. The HSC proliferation
      rates of groups at the end concentrations 144 and 72(g.L(-1)) were 21.62% and
      40.54% respectively, significantly lower than that of normal control
      group(P<0.01). The HSC proliferation rates of groups at the end concentrations
      36, 18 and 9(g.L(-1)) were 54.05%, 45.95% and 51.35% respectively, lower than
      that of control group (P<0.05). When the end concentration was 4.5 g.L(-1), the
      proliferation rate was 83.78%, which appeared no significant differences compared
      with control group. At the same concentrations of 18 g.L(-1), the inhibitory
      effects of Yigan Decoction at 24 h, 48 h and 72 h time point were observed, the
      effects were time-dependent, and reached a peak at 72 h. Meanwhile, it was showed
      that the inducing effects of Yigan Decoction on HSC apoptosis were dose-dependent
      and time-dependent. The apoptosis index(AI) was detected by TUNEL. After Yigan
      Decoction had been incubated for 48 h at the end concentration of 18 g.L(-1), the
      AI (14.5+/-3.1)% was significantly higher than that of control group (4.3+/-1.3)%
      (P<0.01). When visualized under transmission electron microscopy, some apoptotic
      stellate cells were found, i.e. dilated endoplasmic reticulum, irregular nuclei,
      chromatin condensation and heterochromatin ranked along inside of nuclear
      membrane. By flow cytometry detection, after HSC was treated with Yigan Decoction
      at different concentrations of 36, 18 and 9(g.L(-1)) for 48 h, AI (%) were 13.3+/
      3.2, 10.7+/-2.7 and 10.1+/-2.5 respectively, which were significantly higher than
      that of control group(4.1+/-1.9) (P<0.01). At the same concentration of 18 g. L(
      1) for 24h, 48 h and 72 h, AI (%) were 9.3+/-1.8,10.7+/-2.7 and 14.6+/-4.3
      respectively, which were significantly higher than that of control group
      (P<0.01). CONCLUSION: Yigan Decoction could significantly inhibit HSC
      proliferation and increase the apoptosis index of HSC dose-dependently and time
      dependently, which may be related to its mechanism of antifibrosis.

PMID- 12046080
TI  - DNA immunization with fusion genes encoding different regions of hepatitis C
      virus E2 fused to the gene for hepatitis B surface antigen elicits immune
      responses to both HCV and HBV.
AB  - AIM: Both Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are major causative
      agents of transfusion-associated and community-acquired hepatitis worldwide.
      Development of a HCV vaccine as well as more effective HBV vaccines is an urgent
      task. DNA immunization provides a promising approach to elicit protective humoral
      and cellular immune responses against viral infection. The aim of this study is
      to achieve immune responses against both HCV and HBV by DNA immunization with
      fusion constructs comprising various HCV E2 gene fragments fused to HBsAg gene of
      HBV. METHODS: C57BL/6 mice were immunized with plasmid DNA expressing five
      fragments of HCV E2 fused to the gene for HBsAg respectively. After one primary
      and one boosting immunizations, antibodies against HCV E2 and HBsAg were tested
      and subtyped in ELISA. Splenic cytokine expression of IFN-gamma and IL-10 was
      analyzed using an RT-PCR assay. Post-immune mouse antisera also were tested for
      their ability to capture HCV viruses in the serum of a hepatitis C patient in
      vitro. RESULTS: After immunization, antibodies against both HBsAg and HCV E2 were
      detected in mouse sera, with IgG2a being the dominant immunoglobulin sub-class.
      High-level expression of INF-gamma was detected in cultured splenic cells. Mouse
      antisera against three of the five fusion constructs were able to capture HCV
      viruses in an in vitro assay. CONCLUSION: The results indicate that these fusion
      constructs could efficiently elicit humoral and Th1 dominant cellular immune
      responses against both HBV S and HCV E2 antigens in DNA-immunized mice. They thus
      could serve as candidates for a bivalent vaccine against HBV and HCV infection.
      In addition, the capacity of mouse antisera against three of the five fusion
      constructs to capture HCV viruses in vitro suggested that neutralizing epitopes
      may be present in other regions of E2 besides the hypervariable region 1.

PMID- 12046082
TI  - Salvia miltiorrhiza monomer IH764-3 induces hepatic stellate cell apoptosis via
      caspase-3 activation.
AB  - AIM: To investigate the effects of IH764-3 on HSC apoptosis and the expression of
      caspase-3 protein in HSC apoptotic process. METHODS: HSCs were cultured in medium
      with different IH764-3 doses(10 microg.mL(-1) 20 microg.mL(-1) 30 microg.mL(-1)
      40 microg.mL(-1)) and without IH764-3 and HSC proliferation was quantitatively
      measured by (3)H-thymidine incorporation. The morphological changes of HSCs were
      observed with transmission electron microscope after exposure to the dose of 40
      microg.mL(-1) of IH764-3 for 48 hr. The apoptosis rates were detected by annexin
      V/PI and TdT-mediated dUTP nick end labeling (TUNEL). The expression of caspase-3
      protein was determined by flow cytometry. RESULTS: (1) HSC proliferation rates
      induced with different IH764-3 doses (10 microg.mL(-1) 20 microg.mL(-1) 30
      microg.mL(-1) 40 microg.mL(-1)) were significantly reduced compared with that of
      the control group (P<0.01). (2)With the doses above,IH764-3 dose-dependently
      produced HSC apoptosis rates of 6.7%(9.4%) 9.3%(21.6%) 15.1%(27.2%) and
      19.0%(28.4%) respectively by annexin V and PI-labeled flow cytometry assay or
      TUNEL while it was only 2.3%(6.7%) in the control. (3) The expression of caspase
      3 protein in IH764-3 groups was significantly higher than that of the control
      (P<0.05). CONCLUSION: Within the dose range used in present study IH764-3 can
      inhibit HSC proliferation as well as enhance HSC apoptosis. Furthermore IH764-3
      can significantly increase the caspase-3 protein expression.

PMID- 12046083
TI  - Effect of Maotai liquor in inducing metallothioneins and on hepatic stellate
      cells.
AB  - AIM: To explore the possible mechanism why drinking Maotai liquor dose not cause
      hepatic fibrosis. METHODS: After being fed with Maotai for 56 days consecutively,
      the male SD rats were decollated for detecting the biological indexes, and the
      livers were harvested to examine the liver indexes and the level of hepatic
      metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen
      generation were also observed. RESULTS: Hepatic MT contents were 216.0 ng.g(-1)+/
      10.8 ng.g(-1) in the rats of Maotai group and 10.0 ng.g(-1)+/-2.8 ng.g(-1) in the
      normal control group, which was increased obviously in Maotain group (P<0.05). In
      the rats with grade CCL(2) poisoning induced by Maotai, hepatic MT content was
      304.8 ng.g(-1)+/-12.1 ng.g(-1) whereas in the controls with grade CCL(4)
      poisoning, it was 126.4 ng.g(-1)+/-4.8 ng.g(-1) (P<0.05). MDA was 102.0 nmol.g(
      1)+/-3.4 nmol.g(-1) in Maotai group and 150.8 nmol.g(-1)+/-6.7 nmol.g(-1) in the
      control group (P<0.05). When both of the groups were suffering from grade CCL(4)
      poisoning, hepatic MT contents was negatively correlated with MDA (r=-0.8023,
      n=20, P<0.01). The 570 nmA values of each tube with HSC regeneration at
      concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai were 0.818, 0.742,
      0.736, 0.72, 0.682, and 0.604, respectively. From the concentration of 10 g.L(
      1), Maotai began to show obvious inhibitory effects against HSC, and the
      inhibition was concentration-dependent (P<0.05, P<0.01). Type I collagen contents
      in HSC were 61.4, 59.9, 50.1, 49.2, 48.7, 34.4 microg.g(-1) at concentrations of
      0, 10, 50, 100, and 200 g.L(-1) of Maotai. At the concentration of 100-200 g.L(
      1), Maotai had obvious inhibitory effect against the secretion of type I collagen
      (P<0.05). Gene expression analysis was conducted on cells with Maotai
      concentrations of 0, 50, 100g.L(-1) respectively and the ash values of beta-actin
      gene expression were 0.88, 0.74, and 0.59, respectively,suggesting that at the
      concentration of 100g.L(-1), Maotai could obviously inhibit gene expression of
      type I procollagen (P<0.05), but the effect was not obvious at the concentration
      of 50 g.L(-1) (P>0.05). At the concentration of 10 g.L(-1), HSC growth in vitro
      inhibition rates were 16.4+/-2.3 in Maotai group and -8.4+/-2.3 in the control
      group (P<0.05). CONCLUSION: Maotai liquor can increase metallothioneins in the
      liver and inhibit the activation of HSC and the synthesis of collagen in many
      aspects, which might be the mechanism that Maotai liquor interferes in the
      hepatic fibrosis.

PMID- 12046084
TI  - Characteristics and mechanism of enzyme secretion and increase in [Ca2+]i in
      Saikosaponin(I) stimulated rat pancreatic acinar cells.
AB  - AIM: This investigation was to reveal the characteristics and mechanism of enzyme
      secretion and increase in [Ca2+]i stimulated by saikosaponin(I) (SA(I)) in rat
      pancreatic acini. METHODS: Pancreatic acini were prepared from male Wistar rats.
      Isolated acinar cells were suspended in Eagle's MEM solution. After adding drugs,
      the incubation was performed at 37 degrees for a set period of time. Amylase of
      supernatant was assayed using starch-iodide reaction. Isolated acinar single cell
      was incubated with Fura-2/AM at 37 degrees, then cells were washed and
      resuspended in fresh solution and attached to the chamber. Cytoplasm [Ca2+]i of a
      single cell was expressed by fluorescence ratio F340/F380 recorded in a Nikon PI
      Ca2+ measurement system. RESULTS: Rate course of amylase secretion stimulated by
      SA(I) in rat pancreatic acini appeared in bell-like shape. The peak amplitude
      increased depended on SA(I) concentration. The maximum rate responded to 1 x 10(
      5)mol/L SA(I) was 13.1-fold of basal and the rate decreased to basal level at 30
      min. CCK-8 receptor antagonist Bt(2)-cGMP markedly inhibited amylase secretion
      stimulated by SA(I) and the dose-effect relationship was similar to that by CCK
      8. [Ca2+]i in a single acinar cell rose to the peak at 5 min after adding 5 x 10(
      6)mol/L SA(I) and was 5.1-fold of basal level. In addition, there was a secondary
      increase after the initial peak. GDP could inhibit both the rate of amylase
      secretion and rising of [Ca2+]i stimulated by SA(I) in a single pancreatic acinar
      cell. CONCLUSION: SA(I) is highly efficient in promoting the secretion of enzymes
      synthesized in rat pancreatic acini and raising intracellular [Ca2+]i. Signaling
      transduction pathway of SA(I) involves activating special membrane receptor and
      increase in cytoplasm [Ca2+]i sequentially.

PMID- 12046085
TI  - Effect of endotoxin on portal hemodynamic in rats.
AB  - AIM: To study the effects of endotoxin on portal hemodynamic of normal and
      noncirrhotic portal hypertensive rats. METHODS: Normal rats were
      intraperitoneally injected with 0.1, 0.25, 0.5, 1.0, 2.0, 4.0mg.kg(-1) of
      lipopolysaccharide(LPS) respectively, portal vein ligation(PVL) and intrahepatic
      portal occlusion (IPO) rats as well as sham-operated rats were treated with an
      intraperitoneal injection of 1.0mg.kg(-1) of LPS, the portal vein pressure(PVP),
      portal venous flow(PVF), inferior vena cava pressure(IVCP) and portal vein
      resistance(PVR) were detected 4 hours after injection. RESULTS: PVF of the 5
      groups of rats accepting intraperitoneal injection of LPS were increased from
      14.0 to 18.0, 22.2, 26.2, 34.8, 39.6, 38.8 mL.min(-1) 4 hours after injection of
      LPS(P<0.01). PVP of the 4 groups of rats accepting more than 0.1mg/kg.b.w of LPS
      was increased from 1.04 to 1.25, 1.50, 1.80, 1.95, 2.05 kPa(P<0.01). The
      increments of PVF and PVP were in a dose-dependent manner of LPS. PVR of the 5
      groups of rats was decreased from 51 to 42,44,48,45,44,47 kPa.min.L(-1) (P<0.05)
      and no dose-dependent manner was observed. PVF of PVL, IPO and sham-operated rats
      increased from 22.6 to 32.8, 22.0 to 28.0, 14.0 to 34.8 mL.min(-1) (P<0.01), and
      PVP increased from 1.86 to 2.24, 1.74 to 1.95, 1.04 to 1.80 kPa(P<0.01), PVR
      decreased from 71 to 61, 67 to 61, 52 to 44 kPa.min.L(-1) after intraperitoneal
      injection of 1mg.kg(-1) of LPS. The increments of PVF and PVP of PVL and IPO rats
      were significantly less than the sham-operated rats(P<0.01), There was no
      significant difference between the amounts of PVR decreased in the two groups of
      PHT model rats and sham-operated rats(P>0.05) after intraperitoneal injection
      1mg.kg(-1) of LPS. CONCLUSION: Endotoxin could prompt portal hypertension of the
      normal and noncirrhotic portal hypertensive rats by increasing portal blood flow
      mainly.

PMID- 12046086
TI  - The role of endotoxin, TNF-alpha, and IL-6 in inducing the state of growth
      hormone insensitivity.
AB  - AIM: Critical illnesses such as sepsis, trauma, and burns cause a growth hormone
      insensitivity, which leads to an increased negative nitrogen balance. Endotoxin
      is generously released into blood under these conditions and stimulates the
      production of proinflammatory cytokines such as TNF-alpha, IL-6, and IL-1, which
      may play a very important role in inducing the growth hormone insensitivity. The
      objective of this current study was to investigate the role of endotoxin, TNF
      alpha and IL-6 in inducing the growth hormone insensitivity at the receptor and
      post-receptor levels. METHODS: Spague-Dawley rats were injected with endotoxin,
      TNF-alpha, and IL-6, respectively and part of rats injected with endotoxin was
      treated with exogenous somatotropin simultaneously. All rats were killed at
      different time points. The expression of IGF-I, GHR, SOCS-3 and beta-actin mRNA
      in the liver was detected by RT-PCR and the GH levels were measured by
      radioimmunoassay, the levels of TNF-alpha and IL-6 were detected by ELISA.
      RESULTS: There was no significant difference in serous GH levels between
      experimental group and control rats after endotoxin injection, however, liver IGF
      I mRNA expression had been obviously down-regulated in endotoxemic rats. Liver
      GHR mRNA expression also had a predominant down-regulation after endotoxin
      injection. The lowest regulation of liver IGF-I mRNA expression occurred at 12h
      after LPS injection, being decreased by 53% compared with control rats. For GHR
      mRNA expression, the lowest expression occurred at 8h and had a 81% decrease.
      Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up
      regulated after LPS injection and had a 7.84 times increase compared with control
      rats. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it
      did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats.
      Endotoxin stimulated the production of TNF-alpha and IL-6, and the elevated IL-6
      levels was shown a positive correlation with increased SOCS-3 mRNA expression.
      The liver GHR mRNA expression was obviously down-regulated after TNF-alpha iv
      injection and had a 40% decrease at 8h, but the liver SOCS-3 mRNA expression was
      the 4.94 times up-regulation occurred at 40 min after IL-6 injection. CONCLUSION:
      The growth hormone insensitivity could be induced by LPS injection, which was
      associated with down-regulated GHR mRNA expression at receptor level and with up
      regulated SOCS-3 mRNA expression at post-receptor level. The in vivo biological
      activities of LPS were mediated by TNF-alpha and IL-6 indirectly, and TNF-alpha
      and IL-6 may exert their effects on the receptor and post-receptor levels
      respectively.

PMID- 12046087
TI  - Distribution of constitutive nitric oxide synthase in the jejunum of adult rat.
AB  - AIM: To study the distribution of the constitutive nitric oxide synthase (NOS) in
      the jejunum of adult rat. METHODS: The distribution of endothelial NOS (eNOS) was
      detected by immunohistochemistry. Immunofluorescence histochemical dual staining
      technique were used for studying the distribution of neuronal NOS (nNOS) and
      eNOS. The dual stained slides were observed under a confocal laser scanning
      microscope. RESULTS: Positive neuronal NOS (nNOS) and endothelial NOS (eNOS)
      cells were found to be distributed in lamina propria of villi, and the epithelial
      cell was not stained. eNOS was mainly located in submucosal vascular endothelia,
      while nNOS was mainly situated in myenteric plexus. Some cells in the villi had
      both nNOS and eNOS. More than 80% of the cells were positive for both nNOS and
      eNOS, the rest cells were positive either for nNOS or for eNOS. CONCLUSION: The
      two constitutive nitric oxide synthases are distributed differently in the
      jejunum of rat. nNOS distributed in myenteric plexus is a neurotransmitter in the
      non-adrenergic non-cholinergic (NANC) inhibitory nerves. eNOS distributed in
      endothelial and smooth muscle cells of blood vessels plays vasodilator role. eNOS
      and nNOS are coexpressed in some cells of lamina propria of villi. NO generated
      by those NOS is very important in the physiological and pathological process of
      small intestine.

PMID- 12046088
TI  - Evidences for vagus nerve in maintenance of immune balance and transmission of
      immune information from gut to brain in STM-infected rats.
AB  - AIM: To determine whether Salmonella Typhimurium (STM)in gastrointestinal tract
      can induce the functional activation of brain, whether the vagus nerve involves
      in signaling immune information from gastrointestinal tract to brain and how it
      influences the immune function under natural infection condition. METHODS: Animal
      model of gastrointestinal tract infection in the rat was established by an
      intubation of Salmonella Typhimurium (STM) into stomach to mimic the condition of
      natural bacteria infection. Subdiagphragmatic vagotomy was performed in some of
      the animals 28 days before infection. The changes of Fos expression visualized
      with immunohistochemistry technique in hypothalamic paraventricular nucleus (PVN)
      and superaoptic nucleus (SON) were counted. Meanwhile, the percentage and the
      Mean Intensities of Fluorescent (MIFs) of CD4+ and CD8+ T cells in peripheral
      blood were measured by using flow cytometry (FCM), and the pathological changes
      in ileum and mesenteric lymph node were observed in HE stained sections. RESULTS:
      In bacteria-stimulated groups, inflammatory pathological changes were seen in
      ileum and mesenteric lymph node. The percentages of CD4+ T cells in peripheral
      blood were decreased from 42%+/-4.5% to 34%+/-4.9% (P<0.05) and MIFs of CD8+ T
      cells were also decreased from 2.9+/-0.39 to 2.1+/-0.36 (P<0.05) with STM
      stimulation. All of them proved that our STM-infection model was reliable. Fos
      immunoreactive (Fos-ir) cells in PVN and SON increased significantly with STM
      stimulation, from 189+/-41 to 467+/-62 (P<0.05) and from 64+/-21 to 282+/-47
      (P<0.05) individually, which suggested that STM in gastrointestinal tract induced
      the functional activation of brain. Subdiagphragmatic vagotomy attenuated Fos
      expression in PVN and SON induced by STM, from 467+/-62 to 226+/-45 (P<0.05) and
      from 282+/-47 to 71+/-19 (P<0.05) individually, and restored the decreased
      percentages of CD4+ T cells induced by STM from 34%+/-4.9% to original level
      44%+/-6.0% (P<0.05). In addition, subdiagphragmatic vagotomy itself also
      decreased the percentages of CD8+ T cells (from 28%+/-3.0% to 21%+/-5.9%, P<0.05)
      and MIFs of CD4+ (from 6.6+/-0.6 to 4.9+/-1.0, P<0.05) and CD8+ T cells (from
      2.9+/-0.39 to 1.4+/-0.34, P<0.05). Both of them manifested the important role of
      vagus nerve in transmitting immune information from gut to brain and maintaining
      the immune balance of the organism. CONCLUSION: Vagus nerve does involve in
      transmitting abdominal immune information into the brain in STM infection
      condition and play an important role in maintenance of the immune balance of the
      organism.

PMID- 12046089
TI  - Relationship between lymphocyte apoptosis and endotoxin translocation after
      thermal injury in rats.
AB  - AIM: To investigate the relationship between lymphocyte apoptosis in peripheral
      blood, spleen and mesenteric lymph nodes(MLN) and endotoxin translocation after
      thermal injury in rats. METHODS: In a Wistar rat model inflicted with 30% TBSA
      III degree scalding, serum LPS levels in portal vein and vena cava were
      quantified by tachypleus amebocyte lysate (TAL) technique. The analysis of
      peripheral blood lymphocyte was employed in in situ Cell Death Detection Kit and
      evaluated by flow cytometry. Apoptotic lymphocytes in paraffin-embedded spleen
      and MLN sections were examined by histologic analysis, in situ deoxynucleotidyl
      transferase dUTP nick-end labeling (TUNEL) and peroxidase (POD) staining. The
      images were taken by Cooldccd camera system, and the count and optical density
      value (transmission light) of apoptotic lymphocytes were analyzed with software
      Spot and Imagine proplus 4.10a(IPP4.10a). RESULTS: In the period of 3 to 48
      postburn hours (PBHs) serum LPS level (x10(3) EU.L(-1)) in portal vein (2.11+/
      0.02, 5.66+/-0.20, 3.70+/-0.22, 2.56+/-0.28, 0.90+/-0.11) was higher than that in
      vena cava (0.63+/-0.01, 1.53+/-0.18, 0.83+/-0.32, 0.52+/-0.12, 0.23+/-0.02,
      P<0.01), but both increased sharply in postburn rats (P<0.01) and reached a peak
      at 6 PBH. Analysis of apoptotic lymphocytes showed that the proportion (%) of
      postburn apoptotic cells was much higher than that in healthy rats (8.34+/-1.53,
      8.13+/-1.81, 20.77+/-3.94, 23.90+/-3.92, 11.23+/-1.35 and 13.26+/-2.09 at 3, 6,
      12, 24, 48 and 72 PBH, respectively, vs 3.99+/-1.72, P<0.01), especially after 6
      PBH. The concentrations of lymphocytic apoptosis at 12 and 24 PBH were markedly
      higher than that at other time points. Meantime, few apoptotic lymphocytes were
      found in normal MLN, but increased postburn obviously (3+/-1 vs 546+/-83, 285+/
      39, 149+/-30, 58+/-10, 36+/-11 and 33+/-9 in turn, P<0.01), especially at 3 PBH,
      whereas apoptotic lymphocytes were concentrated in splenic cortex before the burn
      and decreased obviously during 72 PBHs (499+/-186 vs 12+/-8, 19+/-15, 12+/-7,
      100+/-15, 123+/-25 and 226+/-26 in turn, P<0.01) though a slight rise was found
      in the medulla after 24 PBH. Optical density of apoptotic lymphocytes was
      significantly reduced in spleen in the 24 PBHs and raised in MLN during 48 PBHs
      than that prior to the burn, respectively. CONCLUSION: Gut-origin LPS is a major
      cause of endotoxemia taken place early in rats following severe thermal injury
      and could induce extensive lymphocyte apoptosis in blood and MLN, which suggests
      an immunosuppression state could follow the initial injury and favores a septic
      state based on apoptotic mechanism.

PMID- 12046091
TI  - The effects of anisodamine and dobutamine on gut mucosal blood flow during gut
      ischemia/ reperfusion.
AB  - AIM: To determine if anisodamine is able to augment mucosal perfusion during gut
      I/R ischemia-reperfusion. METHODS: A jejunal sac was formed in Sprague Dawley
      rat. A Laser Doppler probe and a tonometer were inserted into the sac which was
      filled with saline. The superior mesenteric artery was occluded (SMAO)for 60
      minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO,
      either 0.2 mg/kg of anisodmine or dobutamine was injected into the jejunal sac.
      Laser Doppler mucosal blood flow and regional PCO2 (PrCO2)measurements were made.
      RESULTS: Mucosal blood flow was significantly increased at 30,60 and 90 minutes
      of reperfusion (R30, R60, R90) when intraluminal anisodamine or dobutamine was
      present compared to intraluminal saline only(44+/-3.3% or 48+/-4.1% vs 37+/-2.6%
      at R30, 57+/-5.0% or 56+/-4.7% vs 45+/-2.7% at R60, 64+/-3.3% or 56+/-4.2% vs
      48+/-3.4% at R90,respectively P<0.05). Blood flow changes were also reflected by
      lowering of jejunal PrCO2 measurements after intraluminal anisodamine or
      dobutamine compared with that of the saline controls (41+/-3.1 mmHg or 44+/-3.0
      mmHg vs 49+/-3.7 mmHg at R30,38+/-3.7 mmHg or 40+/-2.1 mmHg vs 47+/-3.8 mmHg at
      R60,34+/-2.1 mmHg or 39+/-3.0 mmHg vs 46+/-3.4 mmHg at R90, respectively,
      P<0.05). Most interesting finding was that there were significantly higher
      mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in
      dobutamine group at 90 minutes of reperfusion(64+/-3.3% vs 56+/-4.2% for blood
      flow or 34+/-2.1 mmHg vs 39+/-3.0 mmHg for PrCO2, respectively, P<0.05),
      suggesting that anisodamine had a more lasting effect on mucosal perfusion than
      dobutamine. CONCLUSION: Intraluminal anisodamine and dobutamine can augment
      mucosal blood flow during gut I/R and alleviate mucosal acidosis. The results
      provided beneficial effects on the treatment of splanchnic hypoperfusion
      following traumatic or burn shock.

PMID- 12046090
TI  - Expression of CD14 protein and its gene in liver sinusoidal endothelial cells
      during endotoxemia.
AB  - AIM: To observe expression of CD14 protein and CD14 gene in rat liver sinusoidal
      endothelial cells (LSECs) during endotoxemia, and the role of CD14 protein in the
      activation of lipopolysaccharide (LPS)-induced LSECs. METHODS: Wistar rat
      endotoxemia model was established first by injection of a dose of LPS (5mg/kg,
      Escherichia coli O111:B4 ) via the tail vein, then sacrificed after 0 h,3h,6h,
      12h, and 24h, respectively. LSECs were isolated from normal and LPS-injected rats
      by an in situ collagenase perfusion technique. The isolated LSECs were incubated
      with rabbit anti-rat CD14 polyclonal antibody, then stained with goat anti rabbit
      IgG conjugated fluorescein isothiocyanate(FITC) and flow cytometric analysis
      (FCM) was performed. The percentage and mean fluorescence intensity (MFI) of CD14
      positive cells were taken as the indexes. LSECs were collected to measure the
      expression of CD14 mRNA by in situ hybridization analysis. The isolated LSECs
      from normal rats were incubated firstly with anti-CD14 antibody, then stimulated
      with different concentrations of LPS, and the supernatants of these cells were
      then collected for measuring the levels of tumor necrosis factor (TNF)-a and
      Interleukin (IL)-6 with ELISA. RESULTS: In rats with endotoxemia, LSECs displayed
      a strong MFI distinct from that of control rats. CD14 positive cells in rats with
      endotoxemia were 54.32%, 65.83%, 85.64%, and 45.65% at 3h, 6h, 12h, and 24h
      respectively, there was significant difference when compared to normal group of
      animals (4.45%)(P<0.01). The expression of CD14 mRNA in isolated LSECs was
      stronger than that in control rats. In LPS group, the levels of TNF-alpha and IL
      6 were 54+/-6 ng.L(-1), 85+/-9 ng.L(-1), 206+/-22 ng.L(-1), 350+/-41 ng.L(-1),
      366+/-42 ng.L(-1) and 103+/-11 ng.L(-1), 187+/-20 ng.L(-1), 244+/-26 ng.L(-1),
      290+/-31 ng.L(-1), and 299+/-34 ng.L(-1), respectively at different concentration
      points. In anti-CD14 group, the levels of TNF-alpha and IL-6 were 56+/-5 ng.L(
      1), 67+/-8 ng.L(-1), 85+/-10 ng.L(-1), 113+/-12 ng.L(-1), 199+/-22 ng.L(-1) and
      104+/-12 ng.L(-1), 125+/-12 ng.L(-1), 165+/-19 ng.L(-1), 185+/-21 ng.L(-1), and
      222+/-23 ng.L(-1), respectively at different concentration points. There was
      significant difference between the two groups (P<0.01). CONCLUSION: LSECs can
      synthesize CD14 protein and express CD14 gene during endotoxemia. CD14 protein
      plays an important role in the activation of LPS-induced LSECs. This finding has
      important implications for the understanding of the mechanisms by which LPS may
      injure liver sinusoidal endothelial cells during sepsis.

PMID- 12046092
TI  - Presence and density of common bile duct microlithiasis in acute biliary
      pancreatitis.
AB  - AIM: Common bile duct microlithiasis (CBDM) is found in majority of patients with
      acute biliary pancreatitis (ABP) and no CBD stones in fluoroscopy during urgent
      ERCP. It is unclear, however, weather CBDM is a cause or the result of the
      disease. This prospective study was done to investigate the presence and density
      of CBDM in patients with ABP, when endoscopic retrograde cholangiopancreatography
      (ERCP) was done in different periods from the onset of the disease. METHODS: One
      hundred fifty one consecutive patients with ABP and no CBDS on ERCP, performed as
      an urgent (< 24h of admission) procedure, (101 - with gallbladder stones, 50 post
      cholecystectomy patients), treated during last 4 years were prospectively
      included to the study. The presence and density of CBDM (cholesterol monohydrate
      crystals-CMCs and calcium bilirubinate granules-CBGs) in bile collected directly
      from common bile duct during ERCP was prospectively calculated according to
      Juniper and Burson criteria. High density of crystals was considered,when we
      found >10CMCs and/or >25 clusters of CBGs on 1 slide. RESULTS: CBD microlithiasis
      was present in given number of patients: on d1-30/34 (88.2%), on d2 41/49
      (83.7%), on d3-23/33 (69.6%), on d4-7-24/35 (68.6%) ( P for trend=0.018). In
      patients with CBD microlithiasis the high density of crystals was observed in
      given number of patients:on d1-27/30 (90%), on d2-34/41 (82.9%), on d3-18/23
      (78.3%), on d4-7-16/24 (66.7%)( P for trend=0.039). CONCLUSION: In patients with
      ABP and no CBDS on ERCP, CBD microlithiasis is observed in the majority of
      patients, especially during the first day of the disease. Density of CBD
      microlithiasis is the highest in the first day of the disease. This suggests that
      CBD microlithiasis can be the cause and not the result of ABP.

PMID- 12046093
TI  - HCV-specific cytokine induction in monocytes of patients with different outcomes
      of hepatitis C.
AB  - AIM: Cytokine release by macrophages critically determines the type of immune
      response to an antigen. Therefore, we studied hepatitis C virus (HCV)-specific
      induction of interleukins-1 beta, -10, -12 (IL-1 beta, IL-10, IL-12), and tumor
      necrosis factor-alpha (TNF-alpha) in monocytes. METHODS: Intracellular cytokine
      expression was studied by flow cytometry in 23 patients with chronic hepatitis C,
      14 anti-HCV seropositives without viremia and 11 controls after stimulation of
      peripheral blood mononuclear cells with recombinant core, NS3, NS4, NS5a and NS5b
      proteins. RESULTS: Patients with HCV viremia revealed greater spontaneous
      expression of IL-1beta, TNF-alpha, and IL-10. Furthermore, greater than twofold
      higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C
      than in the other two groups (P<0.05). In contrast, neither IL-12 nor TNF-alpha
      was induced preferentially. CONCLUSION: In chronic hepatitis C antigen-specific
      cytokine induction in monocytes is apparently shifted towards predominant IL-10
      induction - not counterbalanced by antiviral type 1 cytokines. This may
      contribute to persistent viral replication.

PMID- 12046094
TI  - Coinfection of TT virus and response to interferon therapy in patients with
      chronic hepatitis B or C.
AB  - AIM: To investigate the serum positive percentage of TT virus (TTV) in patients
      with chronic hepatitis B or C and the response of the coinfected TTV to
      interferon (IFN) during IFN therapy for chronic hepatitis B and C. METHODS: We
      retrospectively studied the serum samples of 70 patients with chronic hepatitis
      who had received IFN-alpha therapy from January 1997 to June 2000, which included
      40 cases of hepatitis B and 30 hepatitis C. All the patients had been followed up
      for at least 6 months after the end of IFN therapy. The serum TTV DNA was
      detected using the polymerase chain reaction (PCR) before and every month during
      the course of IFN treatment. RESULTS: TTV infection was detected in 15% (6/40) of
      the chronic hepatitis B group and 30% (9/30) of the chronic hepatitis C group.
      Loss of serum TTV DNA during IFN therapy occurred in 3 of 6 patients (50%) and 6
      of 9 (67%) of hepatitis B and C groups, respectively. Seronegativity of TTV was
      found all during the first month of IFN therapy in the 9 patients. There was no
      correlation between the seroconversion of TTV and the biochemical changes of the
      patients. CONCLUSION: TTV is not infrequently coinfected in patients with chronic
      hepatitis B and C in Taiwan, and more than half of the TTV infections are IFN
      sensitive. However, the loss of serum TTV DNA does not affect the clinical course
      of the patients with chronic hepatitis B or C.

PMID- 12046095
TI  - Epidemiological and histopathological study of relevance of Guizhou Maotai liquor
      and liver diseases.
AB  - AIM: To explore the relevance of Maotai liquor and liver diseases. METHODS:
      Epidemiological study was conducted on groups of subjects, each consisting of 3
      subjects from the Maotai liquor group consisting of 99 individuals and one from
      the non-alcoholic control group consisting of 33 individuals. Liver biopsy was
      performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and
      long history of drinking Maotai liquor. Experimental histopathological study was
      conducted as follows: sixty male Wistar rats were divided into 3 groups randomly
      and fed with Maotai liquor, ordinary white wine, and physiological saline
      respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches,
      then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to
      measure the liver indexes, GSH, and MDA. Histopathological examinations were also
      performed. Another eighty mice were randomly divided into 4 groups and fed with
      Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and
      physiological saline. The animals were sacrificed after 4 weeks and serum ALT was
      determined. Then the livers were harvested and liver indexes and MDA were
      measured. RESULTS: The incidence rate of hepatic symptoms, splenomegaly, liver
      function impairment, reversal of Albumin/Globulin and increased diameter of
      portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 ,
      1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively.
      There was no significant difference between the Maotai group and the non
      alcoholic control group P>0.05 . Various degree of fatty infiltration of
      hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was
      no obvious hepatic fibrosis or cirrhosis. A comparison was made between the
      Maotai liquor group and the ordinary white wine group. It was found that hepatic
      MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai
      group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had
      an obvious decrease in the Maotai liquor group (P<0.05); hepatic GSH were 0.12
      mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/
      0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai
      liquor group (P<0.05). After the 20 rats had been fed with ordinary white wine
      for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of
      hepatocytes, and fibrous septa of varying widths due to hepatic connective
      tissues proliferation were observed; after 12 weeks, the fibrous tissue
      proliferation continued and early cirrhosis appeared. Compared with the ordinary
      white wine group, fatty infiltration was observed in the 8-week and 12-week
      groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor
      group (P<0.05). CONCLUSION: Maotai liquor may cause fatty liver but not hepatic
      fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.

PMID- 12046096
TI  - Clinical significance of plasma D-dimer and von Willebrand factor levels in
      patients with ulcer colitis.
AB  - AIM: To investigate the levels of D-dimer(DD) and von Willebrand factor(vWF) and
      the relationship between DD and vWF in ulcerative colitis(UC) patients. METHODS:
      A total of 29 plasma specimens were obtained from patients with ulcerative
      colitis (male 13, female 16) aged 21-47 years (33+/-11). Disease activity was
      assessed by Truelove-Writeria. Patients with a score of above 5 were regarded as
      having active colitis. Twenty healthy people(male 12, female 8) aged 19-53
      years(31+/-14) served as normal controls. Blood samples were taken from an
      antecubital vein puncture. Blood(1.8 mL) was injected into the tubes containing
      sodium citrate (0.13 mmol/L). The plasma was obtained by centrifugation at 3000
      r.min(-1) for 10 min, and stored at -80 degrees until assayed by ELISA. RESULTS:
      The mean plasma levels of DD and vWF in active UC patients were significantly
      higher than those of the controls (0.69+/-0.41 vs 0.27+/-0.11, P<0.01 143+/-46 vs
      103+/-35, P<0.01). The mean plasma levels of DD in the patients with active
      disease were higher than those with inactive disease(0.69+/-0.41 vs 0.48+/-0.29
      P<0.05). The levels of vWF were not different between active and inactive
      patients. DD levels were positively related to vWF levels( r =0.574, P<0.01).
      There was no significant difference between levels of DD and vWF and the scope of
      disease and sex of the patients. CONCLUSION: vWF is an important feature and a
      good marker of UC intravascular thrombus and endothelial cell dysfunction were
      found in UC patients and the combined test of DD and vWF is helpful to
      distinguish the activity of the UC patients.

PMID- 12046098
TI  - Abortion; liability.

PMID- 12046097
TI  - Voluntary consent to treatment to be obtained; information to be provided.

PMID- 12046099
TI  - Medical treatment; necessary consent in order to act.

PMID- 12046101
TI  - Editorial concerning nurse sedationists.

PMID- 12046100
TI  - Abortion: limitations.

PMID- 12046102
TI  - Re: dangers of intravenous sedation on children.

PMID- 12046103
TI  - Letter from the secretary.

PMID- 12046104
TI  - Employees and access to personnel files.

PMID- 12046105
TI  - Developing processes for third party reimbursement.

PMID- 12046106
TI  - Workers' compensation payment issues.

PMID- 12046108
TI  - MDA Statewide Marketing campaign: update 2002.

PMID- 12046107
TI  - Dr. John Greig: "membership is essential!" Interview by Jeff Mertens.

PMID- 12046110
TI  - Lab technicians: the real story.

PMID- 12046109
TI  - Restoring a smile with a dental implant: a case report.

PMID- 12046111
TI  - Living retiring days fully: a retrospection.

PMID- 12046112
TI  - Prescription drug benefits for seniors and public/private collaboration.

PMID- 12046113
TI  - Healing breathwork.

PMID- 12046114
TI  - Taking stock of our path, purpose and possibilities.

PMID- 12046115
TI  - Beyond ordinary nursing--current and future.

PMID- 12046116
TI  - [HIV/AIDS and hepatitis C transmission by blood transfusion: zero risk does not
      exist].

PMID- 12046117
TI  - [Pulmonary hypertension: recognizing and managing].

PMID- 12046118
TI  - [Nosocomial infections: new prevalence survey].

PMID- 12046120
TI  - [Skin structure and cutaneous scarring].

PMID- 12046119
TI  - [Hospital organ procurement coordinator. Interview by Eric Charles].

PMID- 12046121
TI  - [Different dressing products].

PMID- 12046123
TI  - [Color evaluation of wounds].

PMID- 12046124
TI  - [Pain and wounds: evaluate, prevent, treat].

PMID- 12046125
TI  - [Nutrition and wound scarring].

PMID- 12046126
TI  - [Management of leg ulcers in the elderly].

PMID- 12046127
TI  - [Community and Hospital Nurses United for the Patient: an alternative for
      patients who need dressing care].

PMID- 12046128
TI  - [Epidemiology: another tool for nurses].

PMID- 12046130
TI  - [Disclosure of acquired handicap: between pain and the therapeutic strategy].

PMID- 12046129
TI  - [A nursing care guide and an evaluation scale for better management of the
      chronic pain in neurology].

PMID- 12046131
TI  - [Law no. 2002-3 March 4, 2002 concerning the rights of patients and the quality
      of the health system].

PMID- 12046132
TI  - [Orlistat. A treatment of limited value for obese persons].

PMID- 12046133
TI  - [Dressing at home: the same needs as in the hospital].

PMID- 12046134
TI  - [Patients' rights and quality of health system: citizenship rights authorized by
      the law].

PMID- 12046135
TI  - Chronic disease guidelines and the indigenous Coordinated Care Trials.
AB  - The establishment of the NT Coordinated Care Trials in 1997 provided an
      opportunity for the funding and development of detailed guidelines, designed
      specifically for the Indigenous population, covering screening and clinical
      management of major chronic diseases. All guidelines were incorporated into the
      NT Coordinated Care Trials Information System on the Tiwi Islands and in the
      Katherine West region, and used to generate individual and population care plans.
      In contrast to what is usually written, a broad range of guidelines can be
      developed in a relatively short period of time utilising a dedicated multi
      disciplinary team and local working groups. Having a receptive service delivery
      model, such as the Coordinated Care Trials, allows for a high level of uptake and
      use. The key features were the linking of guidelines to a computerised
      information system that translated them into items of service and presented them
      to the clinician at the time of consultation, combined with ongoing education of
      clinicians and clients.

PMID- 12046136
TI  - More After Hours Medical Service: 'pillars' of success.
AB  - This study aimed to identify and explore the factors that are crucial to the
      successful operation of rural after-hours medical services. It sought to
      determine the attributes that contribute toward the successful operation of after
      hours medical services in rural towns. It drew on computer-assisted telephone
      interviews with stakeholders, and operational, demographic and financial data.
      The findings were brought together and analysed within an integrated framework
      for the guidance of policy makers. In a rural setting, the most important factors
      for a successful after-hours medical service are related to, 'place', 'process',
      'people' and 'time'. These need to be integrated through effective management of
      relationships.

PMID- 12046137
TI  - Factors influencing the utilisation of health services by rural men.
AB  - This research identified the barriers and enablers that influence the utilisation
      of health services by rural men in the Midwest region of Western Australia. The
      methodology was based on participatory action research, including qualitative
      assessments to determine the issues for a larger quantitative study. Four
      variables were identified as predictors for the use of health services: those who
      attended for preventive reasons; those not affected by seasonal work; men who
      thought a medical telephone line was not important; and those who did not
      consider privacy an important issue. Modification of health service delivery to
      men could potentially enhance appropriate utilisation of health services in rural
      areas.

PMID- 12046138
TI  - The management of change in a community mental health team.
AB  - Assertive Community Treatment (ACT) is the most widely studied and well supported
      evidence based community management model for persons with severe mental illness
      (SMI) in the mental health literature. This report details the replacement of an
      unevaluated generic model of case management with ACT in a metropolitan inner
      city area. This is work in progress and detailed patient outcomes are not yet
      available. The steps taken and the problems encountered in changing clinical
      practice are important over and above the intervention itself and are discussed.
      The main difficulty that we encountered was moving staff from focusing on and
      becoming demoralized by potential problems and obstacles to problem solving and
      implementation of the best available solution. Staff were consulted at all stages
      of the project. The use of an 'action research' strategy maximised their sense of
      ownership and ultimately enabled the project to be implemented although in a
      revised format to that originally envisaged. Flexibility in this regard was
      crucial since the budget granted was only 40% of that requested. The original aim
      of having all 3 sector teams of the Inner City Mental Health Service (ICMHS)
      involved did not eventuate due to internal organisational issues and only one
      team undertook to implement the ACT approach.

PMID- 12046139
TI  - Training in routine mental health outcome assessment: the Victorian experience.
AB  - The routine assessment of client outcomes was set as an objective in the
      Australian National Mental Health Policy in 1992. Victoria was the first
      jurisdiction to begin the implementation. This paper reports this process, and
      describes the background to outcome measurement in mental health, assembly of the
      implementation team, certain key concepts, development of the training materials,
      the approach to training, and a brief description of the evaluation. We end with
      a number of observations and recommendations that arose out of the project.

PMID- 12046140
TI  - Entry one: striving for best practice in professional assessment.
AB  - The aim of this study was to develop a best practice model of professional
      assessment to ensure efficient and effective delivery of home-based services to
      frail and disabled elders. In 2000, an innovative model of professional
      assessment was introduced by one of Australia's largest providers of home-based
      care in order to reduce multiple assessments and to reduce the utilisation of
      assessment as a gatekeeping tool for limiting access to services. Data was
      analysed from a random sample of 1500 clients drawn from a population of 5000 as
      well as through the use of a survey tool administered to the Organisation's
      assessment staff and other key stakeholders. Results revealed that, contrary to
      popular belief, carer advocacy plays a significant role in the professional
      assessment process to the point that clients with carers received significantly
      more services and service time that clients without such support. However, if not
      monitored, assessment can also be used as a gate-keeping tool as opposed to one
      that can provide significant benefits to the consumers through comprehensive need
      articulation. We argue that the "professional" approach does not preclude
      empowerment and that assessment should not be used as a gate-keeping tool.

PMID- 12046141
TI  - The nursing workforce in Canada and Australia: two sides of the same coin.
AB  - This paper compares characteristics of the nursing workforce in Canada and
      Australia and provides insights into reasons why the shortage of nurses is more
      critical today than ever before. Workplace issues are discussed in a global
      context. Factors that affect retention and recruitment are described. Factors
      that make the current shortage more serious and different than at other times are
      also presented. Despite the shortage of registered nurses, their replacement with
      unskilled workers jeopardizes the quality of care.

PMID- 12046142
TI  - A retrospective comparative study of patients with chest pain and intra-ward
      transfers.
AB  - This retrospective, comparative survey examined patients who had a discharge
      diagnosis of chest pain and were admitted to The St. George Hospital between July
      1999 to June 2000. The aim was to identify the clinical wards/units to which
      patients were admitted and the number of intra-ward transfers' patients
      experienced during their hospitalisation. Patients admitted to the cardiology
      ward/units and outlying wards were compared to determine the number of intra-ward
      transfers and length of hospital stay. The study found that older patients were
      more likely to be transferred and that the number of intra-ward transfers
      impacted upon length of hospital stay.

PMID- 12046143
TI  - Moving a hospital--a once in a lifetime experience.
AB  - It is a hugely complex task to move a 525-bed acute tertiary health facility to a
      new building whilst continuing to provide services to the public--a task that was
      undertaken at Brisbane's Princess Alexandra Hospital in March/April 2001. There
      were complex issues to manage, ranging from clinical unit interdependence across
      a split campus to the development of detailed plans for transferring telephone
      extensions/personal computers in a "live environment". The success of the
      Princess Alexandra exercise is shown by there having been no adverse effects on
      patients, the lack of negative media attention and the occurrence of only two
      staff injuries during the move. Meticulous planning and good communication with
      staff and stakeholders (other hospitals, general practitioners) supported this
      success. The decision to reduce clinical services where possible during the shift
      was helpful. Understanding the complexity and richness of the information
      technology, the work environment and the human elements on campus was also
      critical to success. One major error was the initial decision to schedule the
      move within weeks of receiving practical completion of the new building. It
      became all too clear in November 2000 that further time was required to
      commission the building. The Transition was therefore rescheduled from January to
      March 2001. This decision was critical to the success of the move.

PMID- 12046144
TI  - Killers in the bush.

PMID- 12046145
TI  - Jaggers in the pokey: understanding tattooing in prisons and reacting rationally
      to it.
AB  - The legalisation of tattooing in prisons, as well as the provision of access by
      inmates to professional tattooists during incarceration, have remained
      contentious issues between custodial and health authorities in most Western
      prisons. This article examines the arguments of both stakeholders as well as the
      attitudes of inmates vis-a-vis tattooing, and suggests a multifaceted approach
      that takes cognisance of inmates' motivation to have prison tattoos, and
      (potential) public health implications of tattooing in correctional settings.

PMID- 12046146
TI  - Why is IT important?
AB  - Healthcare organisations are under pressure to offer improved patient care while
      at the same time attempting to reduce or, at best, manage costs. Technology has
      always played an important role in medicine, helping with devices and improving
      investigations and treatments. In many cases, this technology has helped to boost
      revenues at the same time. Information Technology (IT) has been applied
      traditionally within the administrative areas of the organisation. More recently,
      it is being used within the clinical area and is therefore confronting healthcare
      professionals with both opportunities and challenges in carrying out their tasks.
      This paper attempts to cut through the jargon and hype surrounding trends in
      Information Technology and focus on aspects with which the organisation should be
      concerned.

PMID- 12046147
TI  - Supportive environments for physical activity and the local government agenda: a
      South Australian example.
AB  - In the promotion of moderate physical activity it is increasingly argued that a
      supportive physical environment is a key factor, and that local government is
      ideally placed to play an important role. This study reports on the factors that
      led one local government to take such a leading role. A semi-structured interview
      was conducted to find out why a chief executive officer of a local government
      decided that the creation of supportive environments for physical activity was
      the core business of council. The results show that key ingredients were that
      local government should take a strategic rather than an operational focus on the
      issue, that there should be open organisational structures to allow the various
      functions of local government to work together, and that there must be
      appropriate leadership. The findings suggest ways for engaging local government
      as a key partner in promoting supportive environments that are consistent with
      literature on policy, organisational structure and leadership theory.

PMID- 12046148
TI  - Qualifications and experience: how well prepared are nurse managers compared to
      health service executives?
AB  - The purpose of the paper was to compare the demographic details, educational
      qualifications, professional support and career guidance experiences of two
      groups of health managers as reported in previous research. One group comprised
      nurse managers (Duffield et al 2001) and the other comprised senior health
      administrators (Harris, Maddern & Pegg 1998). Employment and education data from
      self-administered questionnaires were compared. Nurse managers were predominantly
      female (88%), while the administrators were 50% female. The nurse managers,
      although with a relatively equal rate of managerial qualifications as their
      health service counterparts, had not attained as many senior positions in health
      care administration. Over half had not had a mentor. Nurse managers have skills
      attained through their academic studies and experience that cause them to be as
      capable as (if not in some cases better than) health service administrators.
      Increased use of mentoring may provide opportunities for professional advancement
      in wider administrative areas.

PMID- 12046149
TI  - Introducing soft systems methodology plus (SSM+): why we need it and what it can
      contribute.
AB  - There are many complicated and seemingly intractable problems in the health care
      sector. Past ways to address them have involved political responses, economic
      restructuring, biomedical and scientific studies, and managerialist or business
      oriented tools. Few methods have enabled us to develop a systematic response to
      problems. Our version of soft systems methodology, SSM+, seems to improve problem
      solving processes by providing an iterative, staged framework that emphasises
      collaborative learning and systems redesign involving both technical and cultural
      fixes.

PMID- 12046150
TI  - Corruption in the health care system: the circumstantial evidence.
AB  - Health care systems are under intense scrutiny, and there is an increasing
      emphasis on patient safety and quality of care in general. Evidence continues to
      emerge demonstrating that health systems are performing at sub-optimal levels.
      The evidence includes the under-use, over-use and mis-use of health care
      services; new standards asking for respect, dignity, honesty and transparency;
      the corporatization of health; and the existing inequalities in power and health
      outcomes. Recommendations for improving health care often refer to increasing the
      level of collaboration and consultation. These strategies are unlikely to remedy
      the root causes of our ailing health systems if we accept the circumstantial
      evidence that suggests the system is rotten.

PMID- 12046151
TI  - Ethically defensible decision-making in health care: challenges to traditional
      practice.
AB  - The concept of paternalism is deeply entrenched in health care. Decision-making
      about health care can be extremely difficult at times, and many competing
      interests may influence the outcomes. However, ethically defensible practice
      aligns itself with acknowledging the patient's prima facie right to be treated as
      an autonomous individual. This includes the patient's right to make informed
      decisions or to decide that other(s), such as the close family, should make
      decisions on his or her behalf.

PMID- 12046152
TI  - Private health insurance uptake and the impact on normal birth and costs: a
      hypothetical model.
AB  - Recent Australian government policy has encouraged large numbers of women of
      childbearing age to enter private health insurance. This paper describes how
      increased uptake of private health insurance may impact on the rate of normal
      birth, caesarean section and the costs of providing maternity care in low risk
      primiparous women in New South Wales. A hypothetical model was developed using
      data from the NSW Midwives Data Collection. Costs were calculated using data
      established from previous research in NSW (Homer et al 2001). It suggests that,
      as the proportion of low risk primiparous women with private health insurance
      increases, the rate of normal birth may decrease with a subsequent increase in
      rate of caesarean section. As the rate of caesarean section rises, the cost of
      providing intrapartum and postpartum care may also increase. I argue that
      increased rates of private health insurance membership have the potential to
      increase the rate of caesarean section and the cost of providing maternity care
      to low risk women. It is evident that government policy can impact on the outcome
      of maternity care in Australia in ways that might not have been predicted.
      Paradoxically, the care of healthy childbearing women may cost the Australian
      government more to provide in the future.

PMID- 12046153
TI  - Private health insurance: the problem child faces adulthood.
AB  - Since its election to office in 1996, reform of Private Health Insurance (PHI)
      has been the most obvious health policy focus of the Howard Government. The
      reform process has focussed on price, product, promotion, legislation and
      regulation. It has resulted in one of the largest new Commonwealth health outlays
      in recent memory. Health insurance funds have emerged as active purchasers of
      care, not just passive reimbursers of costs. PHI fund reserves have moved from
      precarious liquidity to healthy surplus. Private hospitals are busier than ever
      before, but margins are slim. Anecdotally, public hospitals report little benefit
      to date. Waiting lists have not been reduced, and their budgets are unchanged as
      a result of the $2 Bn allocated under the 30% Rebate scheme. The paper begins by
      describing the origins of the PHI reform. Its objectives, policy initiatives,
      results to date and criticisms are analysed. Criticisms include the actual and
      opportunity costs. Specific concerns remain as to its effectiveness to date in
      reducing pressure on public hospitals, and perceived lack of equity for certain
      client groups. The most significant result is that much of the reform package is
      here to stay including the expensive and much criticised 30% rebate. Like
      Medicare before it, the PHI reforms have achieved bipartisan support. The paper
      concludes by describing future implications for Government, industry, consumers
      and the medical profession.

PMID- 12046154
TI  - The effects of increased market competition on hospital services in Shandong and
      Henan Provinces.
AB  - The Chinese government began a major reform of the hospital sector in the early
      1980s. The main aim was to increase productivity by phasing out prospective
      global budgets from the government, and encouraging between-hospital competition
      for the business of user-pay and insured patients. This goal was to be achieved
      without unreasonable prejudice to the financial sustainability of hospitals or to
      the fairness of access and service provision. We explored the effects of these
      changes by analysing data for four levels of hospital in two of the most populous
      provinces between 1985 and 1999. We used data envelope analysis, and found that
      the majority of hospitals experienced a decline in productivity. Social
      efficiency (measured by the level of provision of unnecessary services) also
      declined, especially in the largest hospitals that could easily increase the use
      of expensive technologies. Most hospitals increased their economic
      sustainability, measured as the ratio between revenue and expenditures. However,
      the lowest-level hospitals experienced stable or reduced sustainability due to
      their inability to compete with marketing by higher-level hospitals. We conclude
      that, although there were many benefits, the overall impact of the introduction
      of market forces may have been negative. An important factor was that not all
      aspects (such as supplier-induced demand) were adequately controlled by
      government agencies. We suggest ways of alleviating the most problematic elements
      of current arrangements.

PMID- 12046155
TI  - Wingecarribee Health Service model for transitional care.
AB  - The Wingecarribee Health Service (WHS) has developed a program of ambulatory care
      different from the commonly accepted models. The program provides a "whole
      service" approach to care, with integration of hospital, allied health and
      community services in partnership with other key stakeholders such as general
      practitioners (GPs) and non-government organisations (NGOs). It departs from the
      medical model and embraces the health service's commitment to a wellness approach
      to care. The program is focused on providing the most appropriate care, in the
      most appropriate location by the most appropriate provider.

PMID- 12046156
TI  - Giving support to disease guidelines. A commentary.
AB  - Whether or not the co-ordinated care models are sustainable in the longer term
      will depend on ongoing funding and on overcoming some of the challenges described
      above. The use of a complete and literal model of care assessment and care
      planning for each individual may not be sustainable for all trials. They will
      require streamlining so that clients with minimal health care needs are not
      subjected to the same comprehensive assessment processes as those with more
      complex needs. Care co-ordination may only have a modest long-term effect, if
      operating problems are not overcome and if the model itself is not fully
      integrated into clinical practices. For this to occur, health centre staff need
      to drive the reform process and need to be supported during this process,
      otherwise the day to day clinical demands will take precedence over care
      planning.

PMID- 12046157
TI  - The Victorian Ambulatory Care Sensitive Conditions study: reducing demand on
      hospital services in Victoria.
AB  - Ambulatory Care Sensitive Conditions (ACSCs) are those for which hospitalisation
      is thought to be avoidable if preventive care and early disease management are
      applied, usually in the ambulatory setting. The Victorian ACSCs study offers a
      new set of indicators describing differentials and inequalities in access to the
      primary healthcare system in Victoria. The study used the Victorian Admitted
      Episodes Dataset (1999-2000) for analysing hospital admissions for diabetes
      complications, asthma, vaccine preventable influenza and pneumococcal pneumonia.
      The analyses were performed at the level of Primary Care Partnerships (PCPs).
      There were 12,100 admissions for diabetes complications in Victoria. There was a
      12-fold variation in admission rates for diabetes complications across PCPs, with
      13 PCPs having significantly higher rates than the Victorian average, accounting
      for just over half of all admissions (6114) and 39 per cent total bed days.
      Similar variations in admission rates across PCPs were observed for asthma,
      influenza and pneumococcal pneumonia. This analysis, with its acknowledged
      limitations, has shown the potential for using these indicators as a planning
      tool for identifying opportunities for targeted public health and health services
      interventions in reducing demand on hospital services in Victoria.

PMID- 12046158
TI  - Description of an early discharge post-acute care program: length of hospital
      stay, patient and carer needs and cost.
AB  - The objective of the project was to evaluate a pilot Post Acute Community Care
      (PACC) program for orthopaedic patients. A series of cross-sectional surveys
      elicited responses of patient and home carer needs and GP and hospital staff
      acceptability while a cost-minimisation analysis compared the average cost of the
      PACC program with general orthopaedic hospital care. Patients were classified
      according to Australian National Diagnosis Related Groups (DRGs). Average length
      of hospital stay in 1998/99 for PACC patients was 7.7 days compared to 12.3 for
      general orthopaedic patients. Only 3% of patients had an unplanned readmission to
      hospital. Patients and carers expressed a number of unmet needs. This study
      confirms the popularity of early discharge schemes with patients, and provides
      little evidence of adverse health outcomes or that the burden of care is shifted
      to carers in a way that is unacceptable for this older population.

PMID- 12046159
TI  - The devil is in the detail: lessons for multi-disciplinary care teams from a
      local evaluation of coordinated care.
AB  - The national evaluation report on the first round of Coordinated Care Trials
      focused on relationships of care coordination from two main perspectives: that of
      the General Practitioner (GP) as care coordinator; and the GP perception of non
      GP care coordinators. As the majority of the Tasmanian care coordinators came
      from a nursing background and dealt with a wide range of health care providers,
      in addition to GPs, a more complex local analysis was required. It was found that
      relations between care coordinators and other health providers varied
      considerably by profession and new strategies were required to ameliorate the
      resulting conflict. This aspect of the local evaluation provides useful lessons
      for analysing and avoiding some sources of conflict in the formation and
      functioning of multi-disciplinary health care teams.

PMID- 12046160
TI  - HealthConnect: a trial of an after-hours telephone triage service.
AB  - This paper describes HealthConnect, an after-hours telephone triage and advice
      service which operated for 15 months in 2000 and 2001. We describe the service,
      discuss utilisation and implementation issues, and conclude with a description of
      the key lessons learned from the trial. The service received over of 12,000
      calls, of which over half were for information rather than immediately seeking
      care. Continuing marketing appears to be required in order to ensure ongoing
      demand for services of this kind. Quality assurance is essential to ensure that
      an optimal service is provided, and staff recruitment and training are critical
      to this. A national standardised approach to services of this kind is desirable
      to provide a consistent service to consumers and realise economies of scale.

PMID- 12046161
TI  - Adolescence and body image.
AB  - Concerns about body image range from a normal desire to look attractive to a
      pathological concern with thinness or physical perfection. Today, more than ever,
      adolescents in America are prone to body image distortions and dissatisfaction.
      The reasons for this are multi-determined and include the influence of the media
      and cultural expectations, as well as a discrepancy between an adolescent's own
      physical characteristics and the expectations of his or her social environment.
      Adolescents with severe body image distortions are vulnerable to developing
      serious psychiatric disorders that can have life-threatening consequences.
      Schools can help by providing guidance and information in a time of uncertainty.

PMID- 12046162
TI  - Lesbian and gay adolescents: identity development.

PMID- 12046163
TI  - U.S. earns disappointing "C" on oral health report card.

PMID- 12046164
TI  - A school nurse perspective on lesbian and gay adolescents: identity development.

PMID- 12046165
TI  - Food allergies and label reading: a healthy relationship.

PMID- 12046166
TI  - Peanut allergy: a deadly game of keep away.

PMID- 12046168
TI  - Training the brain: a new program for struggling students.

PMID- 12046167
TI  - The practice of school nursing in the twenty-first century. Professional issues
      facing today's school nurse.

PMID- 12046169
TI  - Interventions for violence in children and adolescents.

PMID- 12046170
TI  - One in four children affected by parental substance abuse.

PMID- 12046171
TI  - Threat assessment and management.

PMID- 12046173
TI  - May--asthma awareness month.

PMID- 12046172
TI  - Blood glucose testing in the classroom. What are the pros and cons for students
      and for school nurses?

PMID- 12046174
TI  - May 5-11--Food Allergy Awareness Week--national campaign targets "ART" of
      preventing fatalities.

PMID- 12046175
TI  - Commonly asked questions about anaphylaxis.

PMID- 12046176
TI  - Meperidine or morphine for treatment of pancreatic pain?

PMID- 12046177
TI  - Ethics in action. Honoring a daughter's wish to donate her organs.

PMID- 12046178
TI  - You can help prevent falls in older patients.

PMID- 12046179
TI  - Handling chemo safely. Your concern, too.

PMID- 12046180
TI  - The spiritual side of nursing.

PMID- 12046181
TI  - Nuclear attacks.
AB  - The widespread availability of radioactive materials and advancing technology
      have made the prospect of nuclear terrorism a pressing concern. Yet few
      healthcare providers have ever had to treat radiation victims. Here's what you
      must know to manage and treat these victims in the immediate aftermath of an
      attack.

PMID- 12046182
TI  - A guide to mobile chest drains.

PMID- 12046183
TI  - How to handle that staffing predicament.

PMID- 12046184
TI  - The NHS Childcare Strategy.

PMID- 12046185
TI  - Vision 2000 into practice.

PMID- 12046186
TI  - Renewing midwifery and fulfilling our potential.

PMID- 12046187
TI  - Consultant midwives: cameos from clinical practice.

PMID- 12046188
TI  - Changing the way we care for young mothers.

PMID- 12046189
TI  - Rwanda: a personal perspective.

PMID- 12046190
TI  - Renewing midwifery: fulfilling our potential.

PMID- 12046191
TI  - Specialist support for breastfeeding: becoming a lactation consultant.

PMID- 12046193
TI  - The National Congenital Anomaly System--why it needs midwives' support.

PMID- 12046192
TI  - Measuring newborns: does size really matter?

PMID- 12046194
TI  - From grief to new life--the impact of the loss of a baby on future pregnancy.

PMID- 12046195
TI  - Pregnancy as a cause of obesity--myth or reality?

PMID- 12046196
TI  - The pressure is on: midwives and decubitus ulcers.
AB  - Research regarding pressure area care and management in nursing extends back many
      years, but remains relevant and cited today. With relevant knowledge, midwives
      can help prevent the development of pressure sores in the maternity setting.
      Clinical governance and risk management should ensure that the incidence and
      occurrence of pressure sores in the midwifery arena is reported and fed into
      appropriate audit analysis at local, regional and national levels. Midwives need
      to seriously consider the implications of modern midwifery care and management in
      relation to the development of pressure sores in our population. Labour suite,
      high dependency, ward and community areas should include guidelines for the
      prevention, treatment and management of pressure sores, including mattress
      policies. Prophylactic measures and assessment scores could be incorporated into
      partogram documentation in the labour suite and as part of postoperative
      documentation in the ward environment for women who have undergone caesarean
      section. Trusts may find that a link midwife liasing with tissue viability nurses
      proves beneficial. Community midwives should forge links with the district
      nursing services in their Primary Care Trust areas with regard to developing or
      adapting tools. Knowledge of pathophysiology, prophylaxis and subsequent
      management of decubitus ulcers in maternity care is sadly lacking in midwifery
      textbooks. Future authors and editors should include this subject and it should
      feature more prominently in midwifery education curricula. It is clear that there
      is much work to be done in this area, both educationally and clinically. Further
      research is required to evaluate pressure prevention strategies in the midwifery
      arena, including the increasing provision of one-to-one care in labour suite
      units. Improvements in the appropriate prevention and subsequent treatment and
      management of pressure sores will benefit women and help save the NHS hundreds of
      thousands of pounds in treatment and litigation costs.

PMID- 12046197
TI  - CEMD--dark initials in the maternity community.

PMID- 12046198
TI  - Supervision in action: developing a guidance paper on consent and treatment of
      minors.

PMID- 12046199
TI  - Puerperal psychosis.

PMID- 12046200
TI  - Re: Herbal medicines.

PMID- 12046201
TI  - Woman friendly: a personal view.

PMID- 12046202
TI  - [Visit to the Caritas St. Josef Home for the Aged, Cologne: meeting point for
      life].

PMID- 12046203
TI  - [Drinking from the nutrition medicine viewpoint--I: Water is the elixier of life-
      also for the aged].

PMID- 12046204
TI  - [Presenile dementia: old in a young body].

PMID- 12046205
TI  - [Communication with demented patients: speech capacity is lost].

PMID- 12046206
TI  - [Violence in nursing care of patients with dementia: with reference to human
      dignity].

PMID- 12046208
TI  - [Nursing care and dementia management structures in homes for the aged: promoting
      well-being and safety].

PMID- 12046207
TI  - [Strategies against violence in nursing care of the elderly: no power in
      helplessness].

PMID- 12046209
TI  - [Alzheimer disease: information and advice from the internet].

PMID- 12046210
TI  - [Working with relatives: preparing for discharge begins at admission].

PMID- 12046211
TI  - [Nursing care bed as potential risk factor: what industry and marketing can do].

PMID- 12046212
TI  - [Living and nursing in senior home: caught in the network of yearnings].

PMID- 12046213
TI  - [Learning in nursing care: so near and yet so far].

PMID- 12046214
TI  - [References for expert testimony: MDK--speaking the same language with the expert
      witness].

PMID- 12046215
TI  - [Ambulatory geriatric psychiatry centers: cooperation beyond institutional
      limits].

PMID- 12046216
TI  - [Graduate education for nursing in geriatric psychiatry: a curriculum involving
      interpersonal relations].

PMID- 12046217
TI  - [Hypoxic-ischemic encephalopathy in newborns].
AB  - Cerebral hypoxia-ischaemia occurring in the fetus and newborn is a major cause of
      acute mortality and chronic neurologic disability in survivors. Statistics
      suggest an incidence of systemic asphyxia in 1-2/1000 full-term infants and an
      incidence that approaches 60% in very low birth-weight newborns. Although the
      neuropathological features are not exclusively characteristic of full-term or
      preterm babies, it is well known that the gray matter is predominantly involved
      in the term baby while the white matter is damaged in the preterm newborn. In the
      premature infant encephalopathy is often accompanied by peri-intraventricular
      haemorrhage. The different distribution of neuropathologic lesions arising from
      perinatal hypoxia-ischaemia depend on several factors such as intrinsic cellular
      and regional vulnerability, vascular factors, nature and duration of the insult,
      age and maturity of the infant.

PMID- 12046218
TI  - [Current therapeutic approaches of neurologic damage in neonatal asphyxia].
AB  - Perinatal hypoxiaischaemia is a major cause of mortality and neurological
      sequelae in term newborn. Modulation of mechanisms leading to brain cell death,
      in the so-called therapeutic window, may reduce apoptosis and necrosis. Oxidative
      stress and newborn resuscitation, early postnatal pharmacological treatment and
      hypothermic neuroprotection are described. Additional controlled prospective
      trials are warranted on newborns. A combination of neuroprotective agents with
      synergistic effects could represent a potential treatment strategy.

PMID- 12046219
TI  - [Role of neurologic assessment in the evaluation and prognosis of full-term
      newborns with asphyxia].
AB  - Hypoxic-ischaemic encephalopathy, the clinical neurological syndrome that follows
      birth asphyxia, is one of the main causes of neurological sequelae in term
      newborns. Despite the advent of new imaging and neurophysiological techniques in
      the last two decades, the value of the neurological assessment of the newborn has
      not been reduced. The possibility to perform easily serial neurological
      evaluations allows a detailed and non-invasive follow up of the early
      developmental processes, providing reliable prognostic information. In this paper
      we report our experience and a more general review of the literature on the
      prognostic value of the neurological assessment in term newborns with hypoxic
      ischaemic encephalopathy.

PMID- 12046220
TI  - [Neuroimaging techniques for the diagnosis of brain damage in newborns].
AB  - Recently, magnetic resonance (MR) has become the technique of choice in
      evaluating neonatal central nervous system (CNS) diseases. It is the only imaging
      technique that can discriminate myelinated from neonatal unmyelinated white
      matter; it offers the highest sensitivity in detecting acute anoxic injury of
      neonatal brain, and, with proper coils and sequences, it can exquisitely depict
      neonatal brain anatomy and locate pathology. With new generation high-field MR
      imaging units it is now possible to obtain images of molecular diffusion.
      Preliminary reports suggest that diffusion imaging may be useful in early
      detection of perinatal brain ischemia and it is likely to become crucial in the
      effective and safe use of neuroprotective strategies.

PMID- 12046221
TI  - [Role of evoked potentials in neonatal hypoxic-ischemic encephalopathy: review of
      the literature].
AB  - Results of the studies on evoked potentials (EP) in neonates with hypoxic
      ischaemic encephalopathy and their technical feasibility support extensive
      application in neonatal intensive care units. The combined application of visual
      evoked potentials (VEP) and somestesic evoked potentials (SEP) is the method of
      choice for neurodevelopmental prognostication in full-term neonate; especially
      useful in cases with moderate encephalopathy; in preterm neonates EP are
      complementary to head ultrasound scans, particularly early on when the findings
      are in the process of evolution. Brainstem auditory evoked potentials (BAEP) are
      the technique of choice for early identification of sensorineural hearing loss
      necessitating intervention. Long term prognosis on vision and audition is based
      on VEP and BAEP. Studies devoted to definition of the role of EP in selection of
      babies and monitoring neuroprotective intervention are warranted.

PMID- 12046222
TI  - [Free radicals and brain damage in newborns with hypoxic-ischemic lesion].
AB  - Free radicals (FR) are highly reactive chemical molecules containing one or more
      unpaired electrons. Oxygen-derived free radicals, collectively termed reactive
      oxygen species (ROS), are normally produced in living organisms. When over
      produced, they are major mediators of cell and tissue injury. There is a critical
      balance between free radical generation and antioxidant defenses. Oxidative
      stress in vivo is a degenerative process due to the over production and
      propagation of FR reactions. FR reactions lead to oxidation of lipids, proteins,
      polysaccharides and to DNA damage. Newborns and particularly preterm infants are
      very susceptible to FR oxidative damage. In these subjects, there is evidence of
      an imbalance between antioxidant and oxidant-generating systems enhancing oxidant
      injury.

PMID- 12046223
TI  - [Isoprostanes and oxidative stress in brain damage in newborns].
AB  - Isoprostanes are a family of biologically active molecules recently
      characterized, which is emerging as a new class of specific and reliable markers
      of in vivo and ex vivo lipid peroxidation and oxidative damage. These molecules
      are stable, relatively abundant and easily detectable by sensitive and specific
      analytical methods. In the last years, the measurement of their levels in tissue
      homogenates or biological fluids has significantly improved our knowledge on the
      involvement of oxidative stress in several neurological diseases. Here we present
      evidence indicating that isoprostanes can be successfully used also to study the
      mechanisms involved in free radical brain damage following hypoxic-ischaemic or
      inflammatory conditions in newborns and preterm infants.

PMID- 12046224
TI  - [Cognitive and linguistic indexes in children with early hemispheric lesion].
AB  - Prospective studies of development following early focal brain injury have
      identified deficits across a range of cognitive, linguistic and affective
      domains. In most cases these deficits are quite subtle and often not detected on
      standardized behavioral tests. Nonetheless, more detailed tests of
      neuropsychological functioning have documented subtle, persistent profiles of
      impairment. These contrasting findings have been cited in defense of two
      conflicting beliefs: plasticity and hemispheric equipotentiality theories on one
      side and early hemispheric specialization on the other. This paper shows some
      experimental data concerning studies from children with an early focal brain
      lesion. Our aim is to describe the effects determined by the lesion on the
      cognitive development and possible diagnostic and rehabilitative strategies.

PMID- 12046225
TI  - [Effects of socio-environmental factors on neurocognitive performance in
      premature or low-birth weight preschoolers].
AB  - Severely preterm neonates (gestational age < or = 32 weeks) and/or very low birth
      weight (VLBW, with weight at birth < or = 1500 g) are 2% of all newborns, with a
      rising incidence due to the increase of multiple gestations and of pregnancies at
      advanced age. These neonates may be affected by severe neurological pathologies
      (6-10% of cases), but they often have minor disabilities (such as
      distractibility, hyperactivity, learning and social competence disabilities,
      deficit of motor development) difficult to be early diagnosed, and frequently
      recognized only at pre-school or school age. A review of the current knowledge
      about the effects of potential risk factors responsible for deficits of
      neurocognitive development in pre-school age and for postnatal distress of
      mothers, and their inter-correlations, is reported.

PMID- 12046226
TI  - [Animal models of hypoxic-ischemic encephalopathy].
AB  - This review presents the animal models more widely used to study neurological and
      neuropathological outcomes of perinatal asphyxia. Methods used to induce
      hypoxia/ischemia in fetal and newborn non-human primates, lambs, piglets and
      rodents are concisely described, reporting the more relevant neuropathological
      and behavioural findings. In line with human observational data, experimental
      studies indicate that motor behaviour and attentional/cognitive abilities are
      among those behavioural regulations more significantly affected by perinatal
      asphyxia.

PMID- 12046227
TI  - [Impact of socio-environmental factors on physiological processes of brain damage
      recovery: contribution of animal models].
AB  - This review presents the experimental approaches more widely used in animal
      models to investigate possible strategies aimed to stimulate plasticity in the
      nervous system and possibly to increase spontaneous recovery from
      functional/neurological diseases such as neonatal anoxia. Methods used in
      laboratory rodents are briefly described. Attention is focused on possible
      enrichments of the social and physical environment during the development.

PMID- 12046228
TI  - [Neurotrophic factors and brain damage in hypoxic-ischemic encephalopathy: a role
      of nerve growth factor?].
AB  - Hypoxic-ischaemic damage in perinatal brain is a major risk factor of a variety
      of serious human neurological disorders. The mechanisms leading to neuronal
      damage and death remain largely unknown, but animal models indicated that cell
      death via apoptotic mechanism(s) might be one important aspect of these events.
      Neurotrophic factors are protein molecules produced and released by several
      tissues which seem to play a crucial role not only in growth, differentiation and
      function of brain neurons, but also in the mechanisms of neuronal death. Indeed,
      experiments carried out on animal models support the hypothesis that the
      neurotrophins NGF and BDNF are able to prevent and/or reduce neuronal death
      induced by hypoxic-ischaemic events. In this brief review, the established and
      emerging evidences supporting this hypothesis are presented and discussed.

PMID- 12046229
TI  - [Proteic marker of hypoxic-ischemic damage].
AB  - Perinatal hypoxic injury is the major cause of normal neural developmental
      alterations. Recent studies concerning animal models show that an
      hypoxic/ischaemic event triggers a process taking to a synaptic architecture
      reorganization which induces a transient change in the synaptic (synapsin 1, SNAP
      25, APP) and neuronal (MAP2, N-CAM, GAP-43 and presenilins) protein expression.
      Here we review the post-translational modifications of some proteins after
      hypoxic-ischaemic events. A deeper study on synaptic proteins plasticity could
      give an important key for the understanding of the recovery mechanisms of the
      nervous system.

PMID- 12046230
TI  - Standardization of progenitor cell assay for cord blood banking.
AB  - Cord blood has proved itself, if correctly stored with rational criteria, an
      excellent source of stem cells for related and unrelated transplants. It has been
      recently proven that the factor which predicts the best the speed of engraftment
      in cord blood transplants in the dose of progenitor cells injected per kg of body
      weight of the recipient. This result has been obtained thanks to a careful
      standardization of the neonatal progenitor cell assay. This manuscript describes
      such a standardization realized as a joined effort by the Istituto Superiore di
      Sanita, Rome, and the pivotal cord blood bank founded as a feasibility study by
      the National Institutes of Health, Bethesda at the New York Blood Center.

PMID- 12046231
TI  - Developmental profile of serum nerve growth factor levels in Rett complex.
AB  - Rett syndrome (RS) is a progressive neurodevelopmental disorder predominant in
      females, characterised by mental deficiency, stereotyped hand-washing and
      apraxia. Notwithstanding the recent identification of the MECP2 gene likely
      involved in the pathogenesis of SR, the neurobiological bases of this syndrome
      are still largely unknown. Converging evidence shows that the brain levels of
      nerve growth factor (NGF), a neurotrophin regulating the development and
      functioning of central cholinergic neurons, are decreased in RS girls. In this
      study, the serum levels of NGF were measured in classic RS, in the preserved
      speech variant (PSV) and in normal controls. Overall analysis failed to evidence
      significant differences among the three groups. However, whereas NGF levels
      increased significantly with age in controls, the opposite profile was observed
      in classic RS, with a progressive age-dependent decrease of NGF. In PSV subjects
      NGF levels remained constant with age. These findings strengthen the hypothesis
      of NGF involvement in the pathogenesis of RS.

PMID- 12046232
TI  - Toxicity testing in environmental monitoring: the role of enzymatic biosensors.
AB  - Biological toxicity testing is a rapidly expanding field involving numerous
      bioanalytical techniques. The enzymatic biosensors are valuable screening tools
      to identify pollutants and/or toxic agents in the environment and/or in food
      matrices, thus representing a valid alternative to animal testing in analytical
      toxicology. Inhibition based biosensors here presented have been proved to
      represent alternative assays for the toxicity evaluation of warfare agents and
      endocrine disrupting chemicals as well as algal toxins (phycotoxins) in the
      contamined sea foods (mainly clams and other mollusks). Results obtained by
      inhibition studies performed by means of several enzymatic biosensors indicate
      the reliability of the proposed method and the possibility to extend such an
      experimental approach to other toxicants as a simple, rapid and cheap biotest, to
      be used easily also "on the spot".

PMID- 12046233
TI  - [Alkylphenols: assessment of risks for aquatic ecosystems and for human health
      with particular reference to endocrine effects].
AB  - (Alkylphenols: evaluation of the risk to aquatic ecosystems and human health with
      reference to endocrine effects).--Endocrine disrupting chemicals (EDC) are a
      heterogeneous group of substances that can interfere with many endocrine
      functions. Their effects have been demonstrated in different taxa and they are
      suspected to affect human health. Alkylphenols are an important group of EDC.
      They are formed from the degradation of alkylphenol polyethoxylates in the
      environment or in the sewage treatment plants. They are generally characterized
      by a high bioconcentration factor (BCF) and accumulate both in sediments and
      aquatic species. Alkylphenols (APE) show estrogenic activity: studies on fish and
      rodents put into evidence on both reproductive and developmental effects. In a
      recent study, the levels of APE detected in seafood from the Adriatic Sea showed
      a no negligible human health risk for strong fish consumers.

PMID- 12046234
TI  - Active music therapy in the rehabilitation of severe brain injured patients
      during coma recovery.
AB  - Active improvised music therapy may offer an adjuvant from of treatment in the
      early rehabilitation of severe brain-injured patients. Active music therapy
      consists of musical improvisation between patient and therapist by singing or by
      playing different musical instruments, according to the vital functions, the
      neurological conditions and the motor abilities of the patients. We studied 34
      severe brain-injured patients with a mean coma duration of 52 days +/- 37.21 and
      a mean interval from coma onset to the beginning of rehabilitation of 154 days on
      average. Our preliminary results show a significant improvement of the
      collaboration of the severe brain-injured patients and a reduction of undesired
      behaviours such as inertia (reduced psychomotor initiative) or psychomotor
      agitation.

PMID- 12046235
TI  - Do sex assault victims receive adequate care? If not, you risk fines, violations.
AB  - Failure to collect evidence, inadequate care, and delays resulted in a New York
      City hospital being fined for providing inadequate care to a rape victim. These
      problems are common in the emergency department. Avoid asking sexual assault
      victims the same questions repeatedly. Determine the patient's primary concern
      and address it immediately. Examine patients in a private area with adequate
      space.

PMID- 12046236
TI  - Can you really collect copays? Experts say yes.
AB  - Copay collections during the emergency department (ED) visit can provide
      significant additional revenue, since only 35% of copays are paid after the ED
      visit. Collecting copays is not a violation of the Emergency Medical Treatment
      and Labor Act (EMTALA). Use promissory notes, ATMs, and self-addressed stamped
      envelopes to facilitate payment. EDs can obtain $25,000 to $100,000 per month
      from collecting copays.

PMID- 12046237
TI  - Act now to improve your ultrasound program.
AB  - Emergency department ultrasound programs may be shut down if an effective quality
      assurance program is not in place. Videotape every exam so it can be reviewed
      later. Obtain confirmatory tests if you're unsure of results. Have a dedicated
      person responsible for quality assurance.

PMID- 12046238
TI  - Does your documentation satisfy irate colleagues?

PMID- 12046239
TI  - Bioterrorism watch. They don't call it bioterror for nothing: fear is the foe
      when anthrax spores are found within hospital walls.

PMID- 12046240
TI  - Bioterrorism watch. APIC: smallpox plan uses outdated infection control.

PMID- 12046241
TI  - Information technology looms large in the present and future of health care.

PMID- 12046242
TI  - What's a hospital CEO to do?

PMID- 12046243
TI  - [Phototherapeutic keratectomy in the treatment of corneal surface disorders in
      children].
AB  - Retrospective clinical trial evaluated efficacy and safety of phototherapeutic
      keratectomy (PTK) within 35 children (35 eyes) aged 8 to 18 years (mean 12.6
      years). All children had a long time postoperative follow-up ranged from 2 to 5
      years (mean 3.2 years). Indications for PTK in children were: recurrent corneal
      epithelial erosion syndrome, superficial scars after keratitis "e lagophthalmo",
      dry spots and mucous plaques after atopic- vernal eye disease, band keratopathy,
      anterior corneal dystrophies, corneal scars secondary to post-infectious
      keratitis (post-herpes simplex corneal scarring) and following trauma. The aim of
      treatment were to improve visual acuity and to reduce or eliminate subjective
      ocular discomfort-pain, lacrimation and photophobia. Fully informed parents
      consent was done at all cases. There was increased the best spectacle corrected
      visual acuity (BSCVA) in all Children, and episodes of ocular pain, lacrimation
      and photophobia diminished. The mean preoperative BSCVA 6/36 (ranged from 6/9 to
      1/60) improved to mean value 6/12 (ranged from 6/6 to 6/60) as 2-5 years follow
      up postoperatively. Seven children had 5 or more Snellen's lines gain of the
      BSCVA, ten children gained 4 lines, eight children gained 3 lines and five
      children gained 2 lines postoperatively in comparison to their preoperative
      values. At four cases were evaluated only 1 line gain of BSCVA, one eye
      unchanged, and no eye had BSCVA worsened after PTK. Phototherapeutic keratectomy
      in children seems to be an effective and safety procedure in the management of
      suitable anterior corneal disorders. Our clinical results suggest the most
      suitable diagnoses for treatment include recurrent corneal epithelial erosions,
      band keratopathy, dry spots, mucous plaques, anterior corneal dystrophies, and
      anterior post-keratitis and post-traumatic scars.

PMID- 12046244
TI  - [Cataract surgery in 2000].
AB  - The authors evaluate a questionnaire survey concern to cataract surgery in the
      Czech Republic. They present the results of all 58 ophthalmological departments
      where cataract is operated. In the CR in 2000 a total of 49,804 eyes were
      operated. In 94.4% of operations the technique of phacoemulsification was used.
      Primary implantation of an intraocular lens was used in 99% of the operated
      patients. In more than 27% for correction of aphakia a soft intraocular lens was
      used. Almost 30% of the operated patients had one-day surgery. In coming years a
      greater need for these operations may be foreseen. To avoid longer waiting
      periods more financial means will be needed for new types of materials or a
      solution of the problem of financial participation of the patient in meeting the
      costs of surgery.

PMID- 12046245
TI  - [Pseudophakic retinal detachment in relation to complications of cataract
      surgery].
AB  - The authors made a retrospective study in a group of 14 patients operated in 1999
      on account of pseudophakic detachment of the retina (D.R.). They followed up risk
      factors of development of D.R. in conjunction with complications of cataract
      surgery. The investigated factors comprised patients sex and age, type of
      cataract operation and type of implanted lens, complications of cataract surgery,
      time interval between cataract surgery and the development of D.R., pre-operative
      and postoperative visual acuity and type of operation of D.R. In the group there
      was a significant ratio of men (71.4%), the mean age was 60.28 years and 78.6% of
      the patients were referred to our department. Phacoemulsification with
      implantation of IOL was made in 57% of the patients, extracapsular extraction
      with implantation of IOL in 47%. The authors did not find a significant
      difference between the type of cataract surgery with regard to the development of
      D.R. A posterior chamber intraocular lens was implanted in 71% eyes of the group
      while an anterior chamber intraocular lens was used only in 29% of the eyes in
      the group. Complications of cataract surgery were above all ruptures of the
      posterior capsule (64%). Dislocation of the lens into the vitreous body during
      surgery was recorded only in one case (7%) a non-complicated operation of
      cataract was recorded in 28%, incl. one case (7%) where D.R. was preceded by
      laser capsulotomy. The mean time interval between cataract operation and D.R. was
      20.7 months. The visual acuity before surgery of D.R. was 0.24 while after
      surgery it was 0.31. In 50% patients a cryosurgical procedure was used in
      operation of D.R., pars plana vitrectomy as the first operation of D.R. was used
      in 50% of the group. Adherence of the retina after the first operation was
      achieved in 64.2% eyes, after re-operation in 85.7% eyes. The authors did not
      find a significant difference between the type of cataract surgery and type of
      implanted lens as regards anatomical and functional results of surgery of D.R.
      Proliferative vitreoretinopathy and dysfunction of the photoreceptors were the
      main cause of anatomical and functional failure the operation of D.R. in the
      group. The number of pseudophacic D.R. after laser capsulotomy did not exceed the
      number of D.R. after non-complicated cataract surgery in the investigated group.

PMID- 12046246
TI  - [Central serous chorioretinopathy. Treatment, differential diagnosis. Part II].

PMID- 12046247
TI  - [An ophthalmologist diagnosis botulism].

PMID- 12046248
TI  - [The photopic ERG response in diabetes mellitus].
AB  - The authors made photopic ERG examinations according to the international
      standard in 82 diabetic patients. They recorded a significant reduction of
      amplitudes of the b wave in a group of 38 patients who at the time of the
      examination did not have yet any pathological changes on the fundus. Regressive
      analysis did not prove after laser photocoagulation in these patients, contrary
      to a control group and diabetic patients with simple diabetic retinopathy, any
      correlation between the patients age and the extent of the retinal response.
      Photopic electroretinograms must be included in the electrophysiological
      diagnostic arsenal in diabetes.

PMID- 12046249
TI  - [The ocular form of larval toxocariasis in the Czech Republic].
AB  - The damage of the eye is one of the clinical syndromes of the Toxocara infection,
      caused by the migration activity of the Toxocara canis and Toxocara cati larvae.
      Ocular larva migrans (OLM) lesions mostly occur unilaterally and frequently are
      diagnosed as retinoblastoma. The typical symptoms of OLM are presented in our
      publication. The first signs of the ocular infection most often include
      diminished vision, leukocoria, red eye and strabismus. Inflammatory intraocular
      reaction, caused as a response to the antigens, released from dead or dying
      larvae is often diagnosed. The living larvae are observed very rarely. The reason
      and a way of the ocular invasion are still not sufficiently cleared. The
      supposition that the ocular syndrome is caused by migration of single larvae,
      when the immunological response is light, was not reliably verified. Sometimes if
      the infection size was heavy, the eye can be invaded with systemic complications
      as well. The most common laboratory findings include an elevation of the
      immunoglobulins in the serum of the patient and the presence of Toxocara specific
      antibodies response in the vitreous and/or aqueous humor. An analysis of the
      humor in cases of presumptive OLM was made only in 8 patients because not all
      oculists are ready to take this material, mainly in children. Highly sensitive
      assay--ELISA reaction with specific excretory-secretory antigen (TES) was used.
      For discrimination between chronic and recent infection the method of measuring
      IgG avidity was applied.

PMID- 12046250
TI  - [Surgical treatment of traumatic macular holes].
AB  - PURPOSE: To review the anatomic and visual outcomes of patients with traumatic
      macular hole, who underwent vitreoretinal surgery with membrane limitans interna
      (MLI) removal and using autologous serum. METHODS: The retrospective review
      consists of 6 eyes of 6 patients with traumatic macular hole, who underwent pars
      plana vitrectomy with the removal MLI and with using autologous serum. This study
      includes 4 male and 2 female. Ages ranged from 10 to 34 years and all patients
      underwent surgery between February 1997 to October 2000. The time between the
      injury and surgery ranged from 3 days to 3 months. The aetiollogy was 5-times
      blunt trauma with ball during field games and once it was shot injury. The
      initial visual acuity and campimetry were recived and anatomical, functional
      results and campimetry every 3 months after surgery were reviewed. RESULTS:
      Anatomical closure of the macular hole was achieved in 4 (66.6%) of the eyes (in
      1 eye the closure was with pigmented scar). Two patients who have a persistent
      macular hole, underwent this surgery 2 or 3 months after injury. In all 4 eyes
      with anatomic closure of the macular hole was reduction of central scotoma.
      Postoperative Snellen visual acuity improved 3 or mole lines in the 2 eyes.
      CONCLUSION: Our results suggest that the period between injury and vitreoretinal
      surgery is very important for final anatomical and functional results after
      traumatic macular hole.

PMID- 12046251
TI  - [Photodynamic therapy with Visudyne in macular degeneration associated with
      subfoveal classical choroidal neovascularization].
AB  - Photodynamic therapy with the preparation Visudyne (PDT) is the only treatment
      which retards statistically significantly the decline of vision in patients with
      age related and myopic macular degeneration with a subfoveal, predominantly
      classic choroidal neovascularization. The authors present their own experience
      with the treatment of the first 12 patients. During 6-month treatment a loss of
      more than 3 lines of ETDRS optotypes was recorded in two patients (17%). The
      presented results of FTV are consistent with data published abroad. As the one
      year therapeutic results in two patients are encouraging, it will be necessary in
      future to prolong the follow up time and increase the number of patients.

PMID- 12046253
TI  - [Genetically modified organisms--problems and legislation].
AB  - Genetically modified organisms are defined by law as entities capable of
      replication and/or transmission of hereditary material that had been altered by
      the insertion or removal of a DNA fragment. By the EU legal regulation as well as
      by the Czech law, such organisms are considered risky whereas other products of
      breeding, though obtained by, e.g., induced mutagenesis, are claimed as safe.
      Organisms transferred from other ecosystems are also considered safe. The Czech
      law on the use of genetically modified organisms is based on registers of users
      and organisms for specific use. Application for the registration that is valid as
      an approval should be submitted to the Ministry of Environment. The applicant is
      obliged to present the risk assessment of the particular use of genetically
      modified organisms. Genetically modified organisms are connected with certain
      risk to ecology, however health risks are brought about almost exclusively by
      microorganisms. Modified organisms used for food production are thoroughly tested
      for substantial equivalency with standard crops and with respect to health
      parameters of the protein(s) newly introduced due to genetic modification. Detail
      tests as well as their cost are close to the testing of new drugs. European as
      well as Czech rules for food labelling are motivated by the psychology of
      consumers rather than by health impact. They result to absurdities but do not
      meet the task of public psychology. This is why the EU authorities are looking
      for measures to change the present situation that other wise would bring Europe
      well behind the developed countries.

PMID- 12046252
TI  - [Optical coherence tomography in age-related macular degeneration].
AB  - INTRODUCTION: Optic coherent tomography (OCT) is a new non-contact and non
      invasive diagnostic method which visualizes biological tissues in their
      transverse section, similarly as ultrasound examination. It uses however infrared
      radiation and during examination of the posterior pole of the eye it has a
      greater differentiating capacity. THE OBJECTIVE: Of the paper is to compare
      biomicroscopic OCT and angiographic findings in different forms and developmental
      stages of age-related macular degeneration (ARMD), to evaluate the asset of OCT
      for classification and therapy of ARMD. PATIENTS AND METHODS: The authors
      examined 183 patients (266 eyes) with ARMD in different developmental stages. The
      clinical diagnosis of ARMD was established by biomicroscopic and/or angiographic
      examination with fluorescein. RESULTS: In the majority of patients the different
      manifestations of ARMD were associated, and the OCT findings were polymorphous.
      OCT defined more accurately the site and character of changes in the retina and
      adjacent structures, made it possible to assess objectively the thickness of the
      retina and surrounding structures and to detect the presence of fluid and/or
      newly formed intra- and subretinal tissue and tissue benewath the RPE. The CNVM
      classification, introduced by fluorescent angiography differentiating classical
      and occult forms did not have an accurate correlate in the OCT image in our group
      of patients. CONCLUSION: OCT is in the diagnosis and follow up of the development
      of ARMD a suitable supplement of commonly used methods. It provides information
      on spatial relations of pathologically altered tissues. Visualization of the
      retina on the section is particularly valuable when evaluating the results of
      laser or surgical treatment.

PMID- 12046255
TI  - [Carotid sonography and measurement of intima-medial thickness as indicators for
      risk of systemic atherosclerosis].
AB  - Ultrasound of carotid arteries belongs to non-invasive, safe, and comparatively
      inexpensive methods of the subclinical phase arteriosclerosis detection. It
      allows identification of atherosclerosis plaques, which can be found in higher
      numbers in elderly persons. Measurement of intima-media thickness (IMT) belongs
      to the time-proven methods and it represents an independent indicator of the risk
      of the cerebro-vascular event, coronary event including the myocardial
      infarction, and lower limbs ischaemic disease. In asymptomatic forms in persons
      over 45 years, the meticulous IMT examination can bring an additional information
      on the traditional risk factors, specify further the risks of cardio-vascular
      events, and help to elaborate the extent of preventive measures.

PMID- 12046254
TI  - [Effect of products of germ-line and somatic gene mutations on chromatin
      remodeling].
AB  - Chromatin remodeling is engaged in basic cell functions as DNA replication,
      recombination, DNA repair and transcription of genes. Chromatin is remodeled by
      ATP-dependent chromatin remodeling complexes and protein complexes covalently
      modifying histones. Germ-line mutations of the genes coding for proteins which
      participate in chromatin remodeling cause severe developmental diseases and they
      increase a risk of cancer development. Somatic mutations and translocations of
      such genes are associated with cancer development of certain tumors. Chromatin
      remodeling mechanisms can thus be targeted by special strategy of cancer therapy.

PMID- 12046256
TI  - [Treatment of acute lymphoblastic leukemia in adults with seven-drug induction
      therapy and intensive consolidation with or without autologous stem cell
      transplantation followed by maintenance therapy. Experience of a single center].
AB  - BACKGROUND: During the last few years, improvement in prognosis of the adult
      acute lymphoblastic leukaemia (ALL) has been modest. The probability of leukemia
      free survival is 20-40%. Philadelphia-chromosome positive (BCR-ABL positive) ALL
      has the worse prognosis. A single centre experience with treatment of ALL in
      adults is reported. METHODS AND RESULTS: Between April 1997 and July 2000, 15
      consecutive patients with de novo adult ALL (7 T-lineage ALL, 7 B-lineage ALL, 1
      null ALL) begin their treatment with the seven-drug induction regimen (in phase
      I, daunorubicin, vincristine, L-asparaginase, i.v., and prednisone, p.o.; in
      phase II, 6-mercaptopurine, p.o., cytosine arabinoside and cyclophosphamide,
      i.v.) and central nervous system (CNS) prophylaxis (methotrexate and CNS
      irradiation in patients without total body irradiation in conditioning regimen),
      with intensive consolidation (three times high-dose methotrexate and high-dose
      cytarabine, i.v.), and with/out autologous peripheral blood stem cell
      transplantation (PBSCT) followed by maintenance chemotherapy (6-mercaptopurine
      and methotrexate, p.o.). Seven patients received autologous PBSCT. Median patient
      age was 30 years. Three patients were BCR-ABL positive at diagnosis. With median
      follow-up 14 month (range 0.1-46 month), seven (4 T-lineage ALL, 2 B-lineage ALL,
      1 null ALL) out of 15 patients are alive in remission (four of them receiving
      autologous PBSCT). Causes of death were relapse (n = 3), chemotherapy related
      toxicity (n = 2), infection (n = 1), and acute myeloid leukaemia developed 10
      months after autologous PBSCT (n = 1). All BCR-ABL positive patients died.
      CONCLUSIONS: Chemotherapy alone and autologous PBSCT with maintenance therapy may
      be curative for adult patients with ALL. We can recommend these treatment options
      for patients without risk factors in particular.

PMID- 12046257
TI  - [Acute biochemical effects of calcium: comparison of two dosage forms of calcium
      carbonate (powder and effervescent tablets) and milk in healthy women].
AB  - BACKGROUND: The aim of this study was to assess acute biochemical changes after
      the administration of two different pharmaceutical forms of calcium carbonate or
      milk. METHODS AND RESULTS: The group of 12 young (aged 20-27 years) and 12 older
      women (aged 63-71 years). After overnight fasting, each of the volunteers
      received a 1 g of elemental calcium in either form of the tested preparation:
      powder form of calcium carbonate--Vitacalcin pulvis (Slovakofarma, SR) or
      effervescent tablet--Calcium 500 mg Pharmavit (Pharmavit, MR) or in 250 ml of
      milk enriched with the milk calcium complex. Between each test the interval of 1
      2 weeks was held. Samples of blood and urine were taken in the fasting state
      before and during 5.5 h following ingestion of the calcium load. Both calcium
      carbonate and milk induced a significant increase in the serum ionised calcium
      (iCa) and a significant decrease in plasma parathormone level (PTH) in comparison
      with the baseline levels in both groups of women. Comparison between individual
      preparations and between preparations and milk did not reveal any significant
      differences in suppression of PTH. Comparison of the effects between young and
      elderly women did not show any statistically significant difference in any
      measured parameter. CONCLUSIONS: Our results confirmed the good bioavailability
      of calcium from milk and from both calcium preparations in both age groups of
      women. Significantly more frequent hypercalcemia in the young women (p < 0.05)
      and also the slightly higher hypercalciuria occurred after the application of
      calcium in the pharmaceutical form of effervescent tablet than after the
      application of calcium in the form of powder or after the application of milk.

PMID- 12046258
TI  - [The role of protein-RNA reactions during the HIV virus life cycle].

PMID- 12046259
TI  - [Use of hammerhead ribozymes as antiviral tools].

PMID- 12046260
TI  - [Characteristics of the 5' nuclease family].

PMID- 12046262
TI  - [Professor Tomasz Borkowski--obituary].

PMID- 12046261
TI  - [Quercetin: significance in mutagenesis and carcinogenesis].

PMID- 12046263
TI  - [Structure and functions of CD36 protein].

PMID- 12046264
TI  - [Regulation of alternative oxidase activity].

PMID- 12046265
TI  - [Mechanisms for anti-resorptive action of bisphosphonates in bone diseases].

PMID- 12046266
TI  - Making finance work for you.
AB  - Every organization has a process for reviewing requests against their own
      guidelines, which are not always well defined. Normally, all requests must be
      able to demonstrate an adequate financial return on any investment of dollars
      and/or resources. Quality and service improvement benefits sometimes are
      accepted, but often must be translated into documentable dollars and cents. In
      this article, the author shows how understanding the basic concepts of revenue
      and expense is a good first step toward improving your chances of gaining
      approval. Forming an effective two-way partnership with the staff in your finance
      department will improve your chances even more.

PMID- 12046268
TI  - Moving your laboratory? 10 keys to a successful transition.
AB  - We all have been there. Moving, whether it is from one state or town, or just
      across the street, can be chaotic and exhausting. Our possessions are placed in a
      box, loaded with our furniture into a big truck, and transported from one site to
      another. Most of us use this opportunity to sort through old papers, drawers, and
      cabinets, cleaning and throwing out items we no longer will use. If we are well
      organized, things can go smoothly. However, even for the most organized person,
      items get lost or misplaced, tempers get short, and we are disoriented for a few
      days or weeks until everything gets into place and we can reestablish our
      routines. In the summer of 2001, Cleveland Clinic Florida moved their laboratory.
      This article outlines the clinic's experience, offering suggestions for when you
      face your own moving day.

PMID- 12046267
TI  - Implementing a point-of-care testing program in the critical care setting.
AB  - Clearly, there are important reasons for both the critical care area and the
      laboratory to improve efficiencies wherever possible and at the same time
      maintaining or improving quality. POCT, when implemented in a way that fits the
      individual system, can accomplish both of those objectives. By all accounts, the
      trend toward providing POCT will continue, particularly in the critical care
      units where TAT of the most important STAT tests is of the utmost importance in
      providing the best possible patient care. To support that trend, critical care
      clinicians need to closely work with experts in laboratory medicine to bring the
      expertise of the laboratory to the patient's bedside, where quick and accurate
      results are needed. By working together, critical care clinicians and
      laboratorians can create quality POCT programs in the critical care unit, which
      can meet the needs of both clinicians and laboratorians and, most of all, the
      critically ill patients in our care.

PMID- 12046269
TI  - The human genome project: exploring its progress and successes and the ethical,
      legal, and social implications.
AB  - The human genome project (HGP) began in 1990 with a projected completion time of
      15 years. In that time period, the project expects to complete the sequencing of
      the total human genome, develop genetic maps to assign genes to specific regions
      on chromosomes, to identify genes associated with disease, and to develop new
      technologies for furthering genetic research and clinical testing. The project
      also intends to investigate ethical, social, and legal issues as well as to
      provide education about genetics to professionals and to the public. The HGP has
      seen many achievements yet has much to discover before completion. This article
      attempts to review the HGP and discuss its significance and various ethical
      issues in genetics.

PMID- 12046270
TI  - Building relationships to improve quality.
AB  - When three of Canada's leading teaching hospitals merged, creating the University
      Health Network, three unique, new positions were created to improve the
      relationship between the laboratory and clinical staff: clinical liaison/quality
      coordinator, transfusion safety officer, and point-of-care testing/quality
      assurance coordinator. All were prime candidates for taking their technical
      skills and experience beyond the laboratory, and they learned to nurture the new
      relationship formed with clinical staff. In this article, the authors explain how
      some additional skills had to be learned and how new philosophies had to be
      adopted.

PMID- 12046271
TI  - Office technology for managers: keeping up in a constantly changing E-world.

PMID- 12046272
TI  - Correcting technically incorrect information.

PMID- 12046273
TI  - Common cent$ 6: the new rules!

PMID- 12046274
TI  - Laboratory design. Getting off to a good start.

PMID- 12046275
TI  - Multidisciplinary management: why me?
AB  - Laboratory professionals are being asked more and more frequently to spread their
      wings and take on additional responsibilities in the form of multidisciplinary
      management. Multidisciplinary management can be described as the management of
      multiple departments with one or more being outside of the traditional laboratory
      department, such as respiratory care, pharmacy, radiology, or cardiodiagnostics.
      Reasons behind the trend in multidisciplinary management and why laboratory
      professionals often are asked to assume these roles will be explored. This column
      will cover how laboratory managers can prepare for the challenges of
      multidisciplinary management, what skills are necessary for these new roles, and
      how to prepare yourself to be the candidate of choice for these positions when
      they develop. Challenges often encountered will be discussed, including
      suggestions on how to turn potential difficulties into positive growth
      experiences. Hopefully, at the conclusion, you will be able to answer the
      question "Why me?"--either in the form of "Why have I been asked to take on this
      role?" or "Why might I want to pursue such a role with enthusiasm?"

PMID- 12046276
TI  - Health-care managers in the complex world of health care.

PMID- 12046277
TI  - Recent advances in parathyroid disease and parathyroid hormone assays.
AB  - Parathyroid hormone (PTH) regulates extracellular calcium. The physiology and
      pathology of PTH and the many circulating fragments of PTH are reviewed. Various
      PTH assays have been used, leading to the now standard intact PTH (iPTH). The
      recently discovered 7-84 fragment may have profound implications in PTH
      measurement and management, particularly in renal-failure patients. Newer assays
      measuring true PTH, exclusive of this fragment, are appearing on the market and
      may have use in monitoring calcitriol analogue therapy and other settings. Rapid
      PTH assays have application as intraoperative measures of success during excision
      of parathyroid adenomas.

PMID- 12046278
TI  - The pros and cons of point-of-care and core laboratory testing.

PMID- 12046279
TI  - "Just do it": moving the box.

PMID- 12046280
TI  - Pattern of polycyclic aromatic hydrocarbons (PAHs) pollution in communication air
      of Hangzhou, China.
AB  - Nine PAHs were surveyed in communication air of Hangzhou. The results indicated
      that the PAHs pollution is very serious and the total sum of 9 PAHs, on the
      average are 3.39-13.82 micrograms/m3. The PAHs signatures for all streets are
      similar to each other. Multivariate statistical techniques were used to
      investigate source apportionment for PAHs. A factor analysis/multiple regression
      model was successfully applied to the study. The most important three PAHs
      sources in communication air are diesel emission, gasoline engine emission, coal
      burning accounting for 61.1 +/- 6.4%, 19.9 +/- 8.3%, 10.8 +/- 10.8% of total
      PAHs, respectively. The relationship for three source tracers and total PAHs is:
      [PAHs] = 1.471 (+/- 0.155) [Phen] + 2.538 (+/- 2.522) [1 - Mepy] + 2.254 (+/-
      0.943) [Chry] + 1.022 (+/- 1.767).

PMID- 12046281
TI  - Prediction of liquid chromatography retention factors for alpha-branched
      phenylsulfonyl acetates using quantum chemical descriptors.
AB  - The logarithms of retention factors normalized to a hypothetical pure water
      eluent (log kw) were determined on a reversed-phase high-performance liquid
      chromatography(RP-HPLC) column (Li Chrosorb RP-18 column) for 20 new alpha
      branched phenylsulfonyl acetates. The atomic charge method was applied to develop
      quantitative structure-retention relationships (QSRRs). Among the available
      geometric and electronic descriptors, surface area (S), ovality (O), and the
      charge of carboxyl group (Qoc) are significant. In the model, the contribution of
      surface area (S) is the greatest. The molecular mechanism of retention was
      demonstrated through the model. With the correlation coefficient (r2adj, adjusted
      for degrees of freedom) of 0.964, the standard error of 0.164 and the F-value of
      170.39, the model has good predictive capacity.

PMID- 12046282
TI  - Mesoscale meteorological modelling for Hong Kong-application of the MC2 model.
AB  - This paper describes the set-up and application of a non-hydrostatic Canadian
      meteorological numerical model (MC2) for mesoscale simulations of wind field and
      other meteorological parameters over the complex terrain of Hong Kong. Results of
      the simulations of one case are presented and compared with the results of
      radiosonde and aircraft measurements. The model is proved capable of predicting
      high-resolution, three-dimensional fields of wind and other meteorological
      parameters within the Hong Kong territory, using reasonable computer time and
      memory resources.

PMID- 12046283
TI  - Quantification of the effects of management factors on maize (Zea mays L.) and
      cotton (Gossypium hirsutum L.) residues decomposition rate.
AB  - Efforts to quantify management effects on decomposition rate of added substrates
      to the soil is important especially where such information is to be used for
      prediction in mathematical or simulation models. Using data from a short-term (60
      days) greenhouse simulation study, a procedure for quantifying effects of
      management on SOM and substrate decomposition is presented. Using microbial
      growth rate u(q), microbial efficiency in substrate utilization e(q), specific
      decomposition rates for added plant residues to two contrasting soils, red earth
      (Ferrasol) and black earth (Acrisol) were estimated. The treatments included
      straw addition + buried, (T1); straw addition + mineral N (T2); and straw
      addition + tillage, (T3). Sampling was done every 15 days. Straw decomposition
      rate was affected by external mineral N sources (Urea 46% N). Addition of an
      external N source significantly increased decomposition rates. The study could
      not, however, fully account for the effect of tillage on residues because of the
      limited effect of the tillage method due to the artificial barrier to mechanical
      interference supplied by the mesh bags. It is concluded that using few decomposer
      parameters, decomposition rates and consequently SOM trends in a soil system can
      be monitored and quantification of the influence of perturbations on
      decomposition rate of added substrates possible.

PMID- 12046284
TI  - Adsorption of chloroacetanilide herbicides on soil and its components. III.
      Influence of clay acidity, humic acid coating and herbicide structure on
      acetanilide herbicide adsorption on homoionic clays.
AB  - Adsorption of chloroacetanilide herbicides on homoionic montmorillonite, soil
      humic acid, and their mixtures was studied by coupling batch equilibration and FT
      IR analysis. Adsorption isotherms of acetochlor, alachlor, metolachlor and
      propachlor on Ca(2+)-, Mg(2+)-, Al(3+)- and Fe(3+)-saturated clays were well
      described by the Freundlich equation. Regardless of the type of exchange cations,
      Kf decreased in the order of metolachlor > acetolachlor > alachlor > propachlor
      on the same clay. FT-IR spectra showed that the carbonyl group of the herbicide
      molecule was involved in binding, probably via H-bond with water molecules in the
      clay interlayer. The type and position of substitutions around the carbonyl group
      may have affected the electronegativity of oxygen, thus influencing the relative
      adsorption of these herbicides. For the same herbicide, adsorption on clay
      increased in the order of Mg2+ < Ca2+ < Al3+ < or = Fe3+ which coincided with the
      increasing acidity of homoionic clays. Acidity of cations may have affected the
      protonation of water, and thus the strength of H-bond between the clay water and
      herbicide. Complexation of clay and humic acid resulted in less adsorption than
      that expected from independent adsorption by the individual constituents. The
      effect varied with herbicides, but the greatest decrease in adsorption occurred
      at a 60:40 clay-to-humic acid ratio for all the herbicides. Causes for the
      decreased adsorption need to be characterized to better understand adsorption
      mechanisms and predict adsorption from soil compositions.

PMID- 12046285
TI  - Remove volatile organic compounds (VOCs) with membrane separation techniques.
AB  - Membrane separation, a new technology for removing VOCs including pervaporation,
      vapor permeation, membrane contactor, and membrane bioreactor was presented.
      Comparing with traditional techniques, these special techniques are an efficient
      and energy-saving technology. Vapor permeation can be applied to recovery of
      organic solvents from exhaust streams. Membrane contactor could be used for
      removing or recovering VOCs from air or wastewater. Pervaporation and vapor
      permeation are viable methods for removing VOCs from wastewater to yield a VOC
      concentrate which could either be destroyed by conventional means, or be recycled
      for reuse.

PMID- 12046286
TI  - Effects of common inorganic anions on the rates of photocatalytic degradation of
      sodium dodecylbenzenesulfonate over illuminated titanium dioxide.
AB  - Experiments were carried out to study the effects of several anions on the
      photocatalytic degradation rates of sodium dodecylbenzene sulphonate (DBS) with
      TiO2 as catalyst. The anions were added as Na2SO4, NaNO3, NaCl, NaHCO3, NaH2PO4
      and Na3PO4, and two levels of anion content, i.e. 12 mmol/L and 36 mmol/L in
      terms of Na+, were studied. The results revealed that: Cl-, SO4(2-), NO3- and
      HCO3- retarded the rates of DBS degradation to different degrees; PO4(3-)
      increased the DBS degradation rate at low concentration and decreased the rate at
      high concentration; H2PO4- accelerated the rate of DBS degradation. The mechanism
      of the effects of anions on DBS degradation was concluded as the following three
      aspects: anions compete for the radicals; anions are absorbed on the surface of
      catalyst and block the active site of catalyst; anions added to the solution
      change the pH value and influence the formation of .OH radicals and the
      adsorption of DBS on catalyst.

PMID- 12046287
TI  - Description of adsorption of hydrophobic organic compounds on sediment using
      multi-component adsorption model.
AB  - A chemical sequential separation procedure for sediment has been developed for
      the adsorptive investigation of hydrophobic organic compounds(HOCs) including
      four fractions: carbonate, hydrous metallic oxide(ferric oxide, manganese oxide
      and alumina), clay and organic matter. Adsorption isotherms of these hydrophobic
      solute probes, such as hexachloroethane, lindane and 1, 2, 4, 5
      tetrachlorobenzene were measured for model sorbents, model and natural sediment,
      and the latter of which was pretreated with the simplified sequential separation
      method. The linear and Langmuir models are applied to correlate the experimental
      data of humic substance and other model sorbents respectively. Multi-component
      Adsorptive Model (MCAM) was used to simulate adsorption isotherms of model and
      natural sediment. The results reveal that(1) the separation efficiencies of
      carbonate, organic matter, ferric oxide, manganese oxide and alumina are 98.1%,
      72.5%, 82.6%, 93.5% and 83.3%, respectively; (2) except for removing metallic
      oxide, the external structure of sediment is not changed greatly after
      separation; (3) the MCAM correlates the data of adsorption isotherm rather well
      with the maximal relative deviations of 9.76%, 6.78% and 9.53% for
      hexachloroethane, lindane and 1, 2, 4, 5-tetrachlorobenaze in model sediment,
      respectively. The MCAM can clearly give expression to the different adsorptive
      mechanisms for HOCs in organic and inorganic matter, though the experimental data
      in each component are not very accurate due to the sequential separation
      efficiency.

PMID- 12046288
TI  - A novel technology for quick acclimation of an anaerobic microbial consortia used
      for biodegrading teraphthalic acid (TA).
AB  - The seed sludge originated from a methane fermentation reactor was enriched and
      acclimated with TA as sole carbon source under nitrate respiration mode first for
      6 week, and then can be turned to methane fermentation conditions. After 6 weeks
      processing, the specific rate of TA degradation under nitrate respiration mode
      reached 23.8 mgTA/(L.gVSS), more than two times of that under methane
      fermentation mode 11.4 mg TA/(L.gVSS). The TA reductive cleavers' population
      density increased about 6 times and 20 times after 30 days and 90 days
      acclimation. After a total of 90 days for the enrichment and acclimation, the
      fermentative bacteria which originally existed in the seed sludge nearly
      disappeared, and instead of them, the TA reductive and cleaving bacteria group
      was formed in the new consortia, which was confirmed by the MPN counts and roll
      tube counts. Compared with the control experiment, the acclimation period can be
      shortened by about 50%.

PMID- 12046289
TI  - Pulse cleaning flow models and numerical computation of candle ceramic filters.
AB  - Analytical and numerical computed models are developed for reverse pulse cleaning
      system of candle ceramic filters. A standard turbulent model is demonstrated
      suitably to the designing computation of reverse pulse cleaning system from the
      experimental and one-dimensional computational result. The computed results can
      be used to guide the designing of reverse pulse cleaning system, which is optimum
      Venturi geometry. From the computed results, the general conclusions and the
      designing methods are obtained.

PMID- 12046290
TI  - Joint enhancement of lead accumulation in Brassica plants by EDTA and ammonium
      sulfate in sand culture.
AB  - When EDTA was added alone in the Pb-contaminated sand, the plant biomass and the
      total Pb amount in Plant decreased in both species, Brassica pekinensis and B.
      juncea var. multiceps, though the shoot Pb amount increased. In contrast, when
      (NH4)2SO4 was added alone in the Pb-contaminated sand, little effect was observed
      on the shoot Pb amount, though the root Pb amount was significantly increased in
      B. juncea var. multiceps. When amending EDTA and (NH4)2SO4 in combination,
      however, the shoot Pb amount in both species substantially increased, being, on
      an average, 2 times and 9 times higher than that in EDTA alone or (NH4)2SO4 alone
      amended treatment, respectively. The two amendments showed antagonism for plant
      growth, but synergism for Pb bioaccumulation. B. pekinensis showed its highest
      level of shoot and total Pb amount in the treatment amended with EDTA and
      (NH4)2SO4 only a half as much as in the other treatments. It is inferred that the
      mechanisms responsible for the joint-enhanced Pb accumulation might be concerned
      with the acidification of the growth medium, cation exchange reaction and
      relieving EDTA induced toxicity as results by amending ammonium sulfate.

PMID- 12046291
TI  - Morphometric relationships and reproductive maturation of the mudskipper,
      Periophthalmus barbarus from subsistence catches in the mangrove swamps of IMO
      estuary, Nigeria.
AB  - From April 1992 and March 1993, morphometric characteristics and reproductive
      maturation were studied in Periophthalmus barbarus from subsistence catches in
      the mangrove swamps of Imo estuary. Morphometric equations for males and females
      at different stages of ovarian maturation are presented. Generally males were
      significantly heavier in weight than females, but the latter were heavier than
      the former of the same body length. Females with developing and mature ovaries
      were generally heavier than immature females of the same length. Analyses of the
      gonadosomatic index and percentage of mature males and females indicate all year
      round breeding such that: February-May was spawning, June-October postspawning
      and November to January recovery period. Fecundity varied between 900 and 23,933
      eggs per spawn and increased with fish size.

PMID- 12046293
TI  - Ecological and environmental water demand of the lakes in the Haihe-Luanhe Basin
      of north China.
AB  - The purpose of this paper is to present a brief concept of the ecological and
      environmental water demand of lake. The present situation and affecting factors
      of lake ecological system in the Haihe-Luanhe Basin of North China was analyzed.
      The calculating method of the ecological and environmental water demand of the
      lake basis on the water body and the calculating method of the ecological and
      environmental water demand of the lake basis on the aquatic ecosystem, wetland
      and vegetation were compared and discussed. As the examples of Baiyangdian Lake
      and Beidagang Lake in Haihe-Luanhe river basin, the ecological and environmental
      water demand of the two lakes was calculated to be 27 x 10(8) m3. It is 6.75
      times to the water demand according to the calculating method of the ecological
      and environmental water demand of the lake basis on the water body. The research
      result indicated: (1) The calculating methods of the ecological and environmental
      water demand of the lake basis on the aquatic ecosystem should be better than
      only basis on the water body of lake. (2) The data, such as area of the
      vegetation kind around and in the lake, the vegetation coefficient, the
      evaporating amount of the vegetation and the vegetation water demand itself
      around and in the lake are lack and urgent need. Some suggestions for controlling
      and regulating the water resource of the lake in North China were proposed.

PMID- 12046292
TI  - Effects of acid deposition on terrestrial ecosystems and their rehabilitation
      strategies in China.
AB  - South China has become the third largest region associated with acid deposition
      following Europe and North America, the area subject to damage by acid deposition
      increased from 1.75 million km2 in 1985 to 2.8 million km2 in 1993. Acid
      deposition has caused serious damage to ecosystem. Combined pollution of acid
      rain and SO2 showed the obvious multiple effects on crops. Vegetable was more
      sensitive to acid deposition than foodstuff crops. Annual economic loss of crops
      due to acid deposition damage in eleven provinces of south China was 4.26 billion
      RMB Yuan. Acid deposition caused serious damage to forest. Annual economic loss
      of wood volume was about 1.8 billion RMB Yuan and forest ecological benefit loss
      16.2 billion in eleven provinces of south China. Acid deposition in south China
      was typical "sulfuric acid type". According to the thoughts of sustainable
      development, some strategies were brought forward as follows: (1) enhancing
      environmental management, specifying acid-controlling region, controlling and
      abating the total emission amount of SO2; (2) selecting practical energy
      technologies of clean coal, for example, cleansing and selecting coal, sulfur
      fixed-type industrial briqutting, abating sulfur from waste gas and so on; (3)
      developing other energy sources to replace coal, including water electricity,
      atomic energy and the new energy such as solar energy, wind energy and so on; (4)
      in acid deposition region of south China, selecting acid-resistant type of crop
      and tree to decrease agricultural losses, planting more green fertilizer crops,
      using organic fertilizers and liming, in order to improve buffer capacities of
      soil.

PMID- 12046294
TI  - Numerical model of compressible gas flow in soil pollution control.
AB  - Based on the theory of fluid dynamics in porous media, a numerical model of gas
      flow in unsaturated zone is developed with the consideration of gas density
      change due to variation of air pressure. This model is characterized of its wider
      range of availability. The accuracy of this numerical model is analyzed through
      comparison with modeling results by previous model with presumption of little
      pressure variation and the validity of this numerical model is shown. Thus it
      provides basis for the designing and management of landfill gas control system or
      soil vapor extraction system in soil pollution control.

PMID- 12046295
TI  - Addition of anaerobic tanks to an oxidation ditch system to enhance removal of
      phosphorus from wastewater.
AB  - The oxidation ditch has been used for many years all over the world as an
      economic and efficient wastewater treatment technology. It can remove COD,
      nitrogen and a part of phosphorus efficiently. In the experiment described, a
      pilot scale Pasveer oxidation ditch system has been tested to investigate the
      removal of phosphorus from wastewater. The experimental results showed that
      influent total phosphorus(TP) was removed for 35%-50%. After this, two anaerobic
      tanks with total volume of 11 m3 were added to the system to release phosphorus.
      As a result, the TP removal efficiency increased by about 20%. At an anaerobic
      HRT of about 6 hours, a TP removal efficiency of 71% was achieved.

PMID- 12046296
TI  - Start-up strategies of UASB reactor for treatment of pharmaceutical wastewater.
AB  - Two start-up strategies of upflow anaerobic sludge blanket (UASB) reactor for
      treatment of pharmaceutical wastewater were investigated. The results showed that
      both of them were workable. Compared with the strategy that started up the
      reactor directly using chloromycetin wastewater, the strategy that started up the
      reactor first using mixed wastewater and then using chloromycetin wastewater
      could save time by 23%. When the latter strategy was adopted the development of
      sludge activity fluctuated more largely and its final activity was lower, but the
      sludge grew faster in the course of start-up.

PMID- 12046297
TI  - History, development and characteristics of lake ecological models.
AB  - This paper provides some introductory information on the history, development,
      and characteristics of various lake ecosystem models. The modeling of lake
      ecological processes began to gain importance in the early 1960s. There are a
      number of models available today, with varying levels of complexity to cope with
      the variety of environmental problems found in lake environments, e.g.
      eutrophication, acidification, oxygen depletion, wetland management, heavy metal
      and pesticide pollution, as well as hydrodynamic problems. In particular, this
      paper focuses on lake eutrophication and wetland models, as well as addressing
      strategies appropriate for the design and development of reliable lake ecological
      models.

PMID- 12046298
TI  - Composting MSW and sewage sludge with effective complex microorganisms.
AB  - The effects of complex microorganisms in composting process of the municipal
      solid waste (MSW) and sludge were examined through inspecting biomass,
      temperature, oxygen consumption, organic mater, and C/N (the ratio of carbon and
      nitrogen). The experimental results shows: complex microorganisms are effective
      to compose organic matter and speedup composting change into humus.

PMID- 12046299
TI  - Adsorption-desorption behavior of acetochlor to soils in the presence of some
      environmental substances.
AB  - The behavior of herbicide acetochlor adsorption-desorption to soil in the
      presence of humic acid (HA), anionic surfactant sodium dodecylbenzene sulfonate
      (SDBS), cationic surfactant hexadecyltrimethyl-ammonium bromide (HDAB) and NH4NO3
      as a chemical fertilizer was studied. Observed acetochlor adsorption isotherm
      were well described using Freundlich isotherm equation, from which the desorption
      isotherm equation has been deduced. The deduced equation can more directly
      describe acetochlor desorption process. The results showed that the enhance of
      acetochlor adsorption capacity by solid HA was greater than by soluble HA. The
      presence of NH4 NO3 can slightly enhance acetochlor adsorption to soil by
      comparison with that measured in NH4 NO3-free solution. In soil-water system,
      surfactant-acetochlor interaction is very complex, and the surfactant adsorptions
      as well as acetochlor adsorption need to be considered. When acetochlor-soil
      suspensions contained lower concentration SDBS or HDAB (40 mg/L), Kf for
      acetochlor adsorption was decreased in comparison to that measured in SDBS- or
      HDAB-free solution. When acetochlor-soil suspensions contained higher
      concentration SDBS or HDAB (corresponding 1400 mg/L or 200 mg/L), Kf for
      acetochlor adsorption was increased in comparison to that measured in SDBS- or
      HDAB-free solution.

PMID- 12046300
TI  - Response of photosynthesis, morphology and growth of Hedysarum mongolicum
      seedlings to simulated precipitation change in Maowusu sandland.
AB  - Response patters were investigated for seedlings of Hedysarum mongolicum, a
      dominant shrub in Maowusu sandland, to the simulated precipitation change by
      artificially controlling water supply at four levels. Plant growth characters, in
      terms of branch number and length, leaf number and area, and biomass, increased
      while water supply increased. However, the effect of water supply on leaf
      photosynthetic rate was not significant. Root/shoot biomass ratio significantly
      decreased with the increase of water supply, which was considered adaptive
      distribution of biomass investments in the different water supply. Water supply
      obviously affected branching patter. Branch section number, branch number and
      length of the same section enhanced as water supply increased. Branch number and
      length were clearly positive correlation with total and aboveground biomass in
      four water supply treatments. Branch character fully showed plant growth.

PMID- 12046301
TI  - Environmental benefits of underground coal gasification.
AB  - Environmental benefits of underground coal gasification are evaluated. The
      results showed that through underground coal gasification, gangue discharge is
      eliminated, sulfur emission is reduced, and the amount of ash, mercury, and tar
      discharge are decreased. Moreover, effect of underground gasification on
      underground water is analyzed and CO2 disposal method is put forward.

PMID- 12046302
TI  - [Vital changes in corneal structure after LASEK during the early postoperative
      period].
AB  - LASEK (Laser Epithelial Keratomileusis) is a new refractive surgery technique,
      with corneal epithelial flap formation, Excimer Laser photoablation, and
      subsequent flap reposition. Confocal microscopy facilitates in vivo evaluation of
      the corneal structure, i.e., a morphological analysis of its layers, and the
      monitoring of postoperative alterations. PURPOSE: The purpose of the present
      study is to assess the corneal structure in vivo morphological after LASEK
      procedure with the use of confocal microscopy in the early postoperative period.
      MATERIAL AND METHOD: The analyzed group of patients consisted of 50 eyes in 30
      patients who underwent correction of myopia and myopic astigmatism using the
      LASEK procedure. The epithelial flap formation was carried out with the use of a
      20% alcohol solution. The photoablation was performed with the Excimer Laser MEL
      70 G-Scan Aesculap Meditec. Postoperative observations were made using a
      Confoscan 2 (Fortune Technologies). The evaluations were performed on the first
      postoperative day, and then at 1, 2, 4 and 12 weeks following surgery. RESULTS:
      Confocal microscopy revealed some changes in the epithelium and corneal stroma.
      At the site of the photoablation the structure of collagen fibers was blurred,
      with increased reflectivity. No scar tissue was found. The pattern of keratoctic
      nuclei in the anterior corneal stroma was typical for the postphotoablation state
      during the whole observation period. Bowman's membrane and the subepithelial
      nerve plexus were absent in the central part of the cornea. The findings kept
      changing in the course of the follow up time. CONCLUSIONS: Confocal microscopy
      enables the monitoring of changes, which occur in the corneal structure after
      LASEK refractive procedures; this facilitates the evaluation of corneal healing.
      LASEK allows for prompt stabilization of the epithelial structure and the
      anterior corneal stroma. No overproduction of collagen fibers was observed at the
      photoablation area during the healing process.

PMID- 12046303
TI  - [Treatment of dislocated lenses in patients with Marfan's syndrome using
      vitrectomy and intraocular lenses].
AB  - PURPOSE: To evaluate results of surgical complex treatment of lens dislocation in
      Marfan syndrome cases. MATERIAL AND METHODS: Nineteen eyes of 13 patients were
      operatively treated for lens dislocation. Pars plana vitrectomy was done in all
      eyes. Dislocated lenses were removed by lensectomy in 5 eyes and with an
      intracapsular method in 14 eyes. The scleral fixation technique was used for
      primary posterior chamber intraocular lens implantation in 18 eyes, and one eye
      remained aphakic. Time of observation ranged between 6 and 71 months (mean 3.5
      years). RESULTS: All eyes achieved improvement in visual acuity or good
      preoperative visual acuity was maintained. The vision between 6/6 and 6/8 was
      achieved in 14 patients. There were no serious intraoperative or early
      postoperative complications. Retinal detachment appeared in two eyes in a long
      observation time and it was successfully operatively treated. The not good visual
      results were due to amblyopia (n = 2), complications of retinal detachment
      surgery (n = 2) and glaucomatous optic disc atrophy coexisting with macular
      degeneration (n = 1). CONCLUSIONS: Pars plana vitrectomy and primary scleral
      fixated IOL implantation gives quick and good visual rehabilitation in adult
      patients with Marfan's syndrome. The described surgical method is complex and
      need a prolonged operative time, but gives very good functional results and very
      few complications.

PMID- 12046305
TI  - [Results of treating retinal redetachment following silicone oil removal].
AB  - PURPOSE: The assessment of anatomical and functional results in the treatment of
      retinal redetachment after silicone oil removal (OR). MATERIALS: Between November
      1992 and October 1996 silicone oil was removed from 104 eyes (98 patients).
      Retinal redetachment occurred in 11 eyes, mostly within 1 month after silicone
      oil removal. METHOD: Revitrectomy with silicone oil tamponade was performed in
      all cases. RESULTS: Retinal attachment was achieved in 8 cases (73%)
      postoperatively, but only three eyes achieved the same visual acuity as before
      SOR. Functional results occurred worse than previous SOR in other patients.
      Visual acuity 1/60 or better was achieved in 6 cases. CONCLUSIONS: Our
      observations demonstrate that revitrectomy with silicone oil endotamponade is an
      effective treatment for retinal redetachment after SOR, even if functional
      results are not as good as anatomical.

PMID- 12046304
TI  - [Vitrectomy in treatment of idiopathic and secondary pre-retinal fibrosis].
AB  - PURPOSE: To present the results of vitrectomy in the management of preretinal
      fibrosis. MATERIAL AND METHODS: 45 patients with preretinal fibrosis treated with
      vitrectomy were analysed. 33 of them were treated from 1997 to 1998 in
      Ophthalmology Dept. University of Heidelberg (Germany) and 12 were treated from
      1998 to 1999 in the 1st Eye Hospital Lublin University School of Medicine. The
      reason for preretinal fibrosis: idiopathic-22 patients, retinal detachment--16,
      retinal vein occlusion--2, trauma--2, uveitis-1, perivasculitis--1, alopecia--1.
      RESULTS: Due to applied treatment 27 patients (60%) showed visual improvement, 13
      patients (29%) had the same visual acuity before and after vitrectomy and 5
      patients (11%) noticed a decrease of visual acuity after the treatment.
      CONCLUSIONS: Vitrectomy is an effective method of treatment of patients with
      preretinal fibrosis. In cases with no improvement of visual acuity after surgery,
      vitrectomy could reduce a metamorphopsia.

PMID- 12046306
TI  - [Use of retinotomy for retinal redetachment in the silicone oil filled eye].
AB  - PURPOSE: Retinal redetachment after primarily successful vitreous surgery with
      silicone oil tamponade is quite often observed. Extensive peripheral retinotomy
      is required. The aim of our study is to present the results of relaxing
      retinotomy. MATERIAL AND METHODS: 94 consecutive patients who underwent
      retinotomy for retinal redetachment in the silicone oil filled eyes were
      examined. Indications for this procedure were: proliferative vitreoretinopathy
      (81.1%), trauma (12.6%) and diabetic retinopathy (6.3%). These eyes were
      previously treated with scleral buckling, vitrectomy, membrane peeling and
      silicone tamponade without success. RESULTS: After a minimum of 6 months follow
      up, the retina was completely attached in 73 (76.8%) cases. Sixty three (66.3%)
      eyes achieved final visual acuity 1/50 or better, and 37 (38.9%) achieved visual
      acuity of 5/50 or better. If the size of retinotomy was < 180 degrees minimal
      visual acuity 5/50 was observed in 40% and if retinotomy size was 180 degrees-360
      degrees this visual acuity was achieved in 38.7% of cases. CONCLUSIONS:
      Retinotomy can be an effective procedure in cases of repeated retinal detachment
      in the silicone oil filled eyes. Both, timing of this procedure and extent of
      retinotomy have no influence on final functional results.

PMID- 12046307
TI  - [Evaluation of silicone oil removal from eyes treated with retinotomy].
AB  - PURPOSE: Long-term silicone oil tamponade may resulting late complications. The
      aim of our study is to find out the results of silicone oil removal in eyes
      treated with retinotomy. MATERIAL AND METHODS: Between January 1991 and December
      1999 37 patients (37 eyes) were given silicone oil removal after retinotomy. The
      indications for vitrectomy with silicone oil tamponade and retinotomy were:
      rhegmatogenous retinal detachment (78.4%) and trauma (21.6%). Completion retinal
      attachment within at least 3 months without reproliferations indicated for
      silicone oil removal. RESULTS: With a minimum of 6 months process follow-up the
      retina was attached in 36 cases (97.3%). 29 (78.4%) eyes achieving final visual
      acuity 1/50 or better. Visual acuity remained unchanged in 64.9% cases. Minimal
      visual acuity 5/50 was achieved in 47.1% of eyes with retinotomy size smaller
      than 180 ae and in 40% of eyes with retinotomy size 180ae-360ae. Visual acuity at
      least 1/50 was achieved in 72.2% of eyes where silicone oil tamponade remained
      shorter than 6 months and in 84.2% when longer than 6 months. CONCLUSIONS:
      Silicone oil removal leads to the stabilisation of visual acuity in majority of
      eyes. Final visual acuity does not correlate with either the retinotomy size or
      with the duration of silicone oil tamponade. Risk of retinal redetachment after
      silicone oil removal in eyes treated with retinotomy may result in similar
      symptom as in eyes treated without retinotomy.

PMID- 12046308
TI  - [Image of optic nerve disc with laser scanning tomography and results of static
      perimetry in children with juvenile glaucoma].
AB  - The aim of our research was to estimate the correlation between optic nerve head
      parameters examined with laser scanning ophthalmoscope and results of central,
      visual field (MD and PSD) in the youth and the evaluation the role of this
      correlation in juvenile glaucoma early diagnosis. MATERIAL: Three groups of
      patients. Group I consisted of 32 eyes (16 children) with juvenile glaucoma in
      which trabeculectomy was performed. There were 72 eyes of 32 children with
      glaucoma juvenile suspect in the group II. Control group (III) contained 20 eyes
      of 10 children without glaucoma. The age of patients ranged from 9 to 18 years.
      The mean intraocular pressure was 16 mmHg in the I group, 18 mmHg in the II group
      and 15.6 mmHg in the III group. Simple Regression Analysis of mean values of
      biomorphometric parameters of optic nerve head for Mean Defect of central visual
      field was used in all three groups. RESULTS: The statistically significant
      correlation between Vol. B and MD was observed in the I group. There was no such
      correlation in the II group, but correlation between Av. Sl. and MD was
      presented. In the III group mean value of MD was the smallest one and correlated
      with Vol. B. Statistically significant correlation between mean values of PSD and
      Vol. B was observed in the I and II group, between PSD and Vol. A in group III.
      CONCLUSION: There was the correlation between optic nerve head parameters and
      mean deviation of retinal sensitivity of central visual field in the youth. This
      examination can be helpful in early diagnosis of primary juvenile glaucoma.

PMID- 12046309
TI  - [Use of amniotic membrane transplantation for treating bullous keratopathy].
AB  - One of the complications of cataract surgery is bullous keratopathy, which is the
      result of decompensation of the corneal endothelium. The clinical signs are
      manifested in stromal and epithelial edema with bullae producing. The amniotic
      membrane, which is taken from the placenta of young mothers during the caesarean
      section, may have beneficial influence on the process of healing the corneal
      structure. The study aimed to evaluate effectiveness of bullous keratopathy
      treatment using amniotic membrane transplantation, as an alternative method of
      treatment after cataract surgery. MATERIAL AND METHODS: The amniotic membrane
      transplantation was performed in 18 eyes of 18 patients (10 females and 8 males),
      aged 62 to 85 with the bullous keratopathy. After removing the pathologically
      changed epithelium, the amniotic membrane was covered on cornea in local
      anesthesia, using interrupted sutures 10.0 nylon. A therapeutic contact lens were
      applied. Control examinations were performed 3, 6 and 12 weeks after the
      operation. The best corrected visual acuity was evaluated. The local state was
      investigated using slitbiomocroscopy and confocal microscopy. RESULTS: In all the
      patients' regression of subjective complaints was observed (pain, light
      sensitivity and tearing). In 12 cases improvement of visual acuity was achieved.
      The evaluation of corneas in slit biomicroscopy revealed greater clarity and less
      corneal edema. On confocal microscopy, decrease in blurred collagen fibers and
      background illumination were observed. The epithelium contained cystic structures
      (blisters) in 6 cases only. The endothelial cells were pleomorphic and
      polymegathic. CONCLUSION: The amniotic membrane transplantation is an effective
      method of treatment for bullous keratopathy and has beneficial influence on the
      process of corneal healing and the improvement of visual acuity and diminish
      subjective symptoms.

PMID- 12046310
TI  - [Acute ophthalmology clinic in the new system of organized health care].
AB  - PURPOSE: To analyse possibilities, needs, expenses and perspectives of the
      emergency service in ophthalmology clinic. MATERIAL AND METHODS: The number of
      patients were treated and diagnosis profile set. It has been analysed in
      emergency service in ophthalmology clinic. The calculation of patient's need and
      hospital operating costs has been performed. RESULTS: Only a few patients needed
      high specialist rescue of ophthalmology department. CONCLUSION: The system in
      which every patient has a possibility to go to the emergency service in
      ophthalmology department of hospital requires urgent changes. This system is too
      expensive for hospital and does not solve the problem who should take care of the
      patient: a general practitioner, out-patients ophthalmologist or other
      physicians.

PMID- 12046311
TI  - [Posterior uveitis in a 47-year old patient infected with HIV--case report].
AB  - PURPOSE: To report the case of posterior uveitis associated with HIV infection
      and to discuss contemporary references on the topic. CASE REPORT: A 47-years old
      woman with asymptomatic HIV infection developed acute posterior uveitis. The
      examinations for infections with CMV, Toxoplasma gondii, Treponema pallidum and
      Mycobacteria were negative. After failure of empirical treatment with
      antibiotics, ganciclovir and steroids antiretroviral treatment with three drugs
      was initiated on the patient. The ophthalmologic examination disclosed
      significant improvement after two weeks of the treatment. There have been no
      evidences of inflammatory disease in the eyes for 12 weeks from the starting of
      antiretroviral therapy. The immunologic and virologic parameters showed good
      control of HIV infection. CONCLUSIONS: Infection with HIV appears to be a cause
      of uveitis.

PMID- 12046312
TI  - [Uveal effusion syndrome--case report].
AB  - The history and clinical findings of 60-year old man with effusion syndrome are
      presented. The uveal effusion syndrome typically affects healthy middle age men
      and causes recurrent, spontaneous, serous retinal and cilio-choroidal detachments
      which, often results in significant visual impairment. In addition, to the
      general clinical examinations, indirect ophthalnoscopy, fundus fluorescein
      angiography, ultrasonography and MRI are used to make definitive diagnosis.
      Annular cilio-choroidal detachment, shifting non-rheumatogenous retinal
      detachment, unremarkable inflammation in the anterior segment and normal
      intraocular pressure are the key features of the idiopathic uveal effusion
      syndrome. The fundus change is characterized by the "leopard-spot".

PMID- 12046313
TI  - [Use of enzyme in vitreoretinal surgery].
AB  - The aim of using enzymes in vitreoretinal surgery is to facility PVD and create
      pharmacological vitrectomy. It can be achieved by liquefying the gel structure of
      the vitreous (synchisis) and weakening of adherence of the posterior vitreous
      cortex to retina (syneresis). The article reviews currently used enzymes in
      vitreoretinal surgery (plasmin, hyaluronidase, dispase, chondroitinase,
      collagenase, urokinase, TPA--tissue plasminogen activator) and presents potential
      profits and side-effects related to their use. Although the day when vitreous
      surgery is replaced by pharmacological vitreolisis remains still as a future,
      these enzymes hold great promise. Additionally it has been proved that enzymes
      can be used successfully as an intraoperative adjuvant in vitrectomy.

PMID- 12046314
TI  - [The role of light in pathogenesis of refractive errors].
AB  - PURPOSE: To present and account the results of newest experimental and clinical
      investigations on the subject of the light effect on the creation of refractive
      errors. MATERIAL AND METHODS: A review of literature concerning the role of the
      light in the refractive errors' pathogenesis has been performed. RESULTS: The
      influence of continuous light and night adaptation on the eyeball development as
      well as on the creation of refractive errors in experimental conditions are
      discussed. The anatomical and biochemical changes taking place in the course of
      experimental myopia are described. The entities of diseases predisposing to the
      creation of myopia are characterized. The results of the newest clinical
      investigations in which was shown that myopia and hyperopia might be associated
      with sleeping in lighted rooms up to the age of two are presented as well as
      accounted. CONCLUSIONS: Light and darkness play an important role in the proper
      eye development. Disturbance of the diurnal cycle over the time during which
      refraction forms may create refractive errors.

PMID- 12046315
TI  - [History of excimer laser refractive surgery in Poland].
AB  - First publication about excimer laser in 1983 became the beginning of laser
      refractive surgery. At the beginning excimer laser was used for PRK procedure for
      correction of myopia. Laser refractive surgery developed rapidly in 90-ties when
      LASIK and LASEK procedures started to be used for any kind of refractive errors.
      In Poland laser refractive surgery begun to be used in 1990.

PMID- 12046316
TI  - [LASEK--new laser refractive surgical technique. Personal experience].
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      refractive error correction LASEK. MATERIAL AND METHODS: 115 eyes were analyzed
      after LASEK. The eyes were divided into 4 groups (myopia, myopic astigmatism,
      hyperopia, hyperopic astigmatism). The follow-up has taken 3 months. The
      effectiveness of this method was evaluated on the basis of the best visual acuity
      without correction after LASEK procedure, compared to the best visual acuity with
      correction before LASEK. The course of the healing process, the state of cornea
      and subjective symptoms were also evaluated. RESULTS: After 2 weeks in whole
      group the mean UCVA was in the same range of values compared with the BCVA before
      the operation. There were no postoperative complications observed. CONCLUSION: On
      the basis of our own observations we can say that LASEK is an effective and safe
      method for correction of refractive errors.

PMID- 12046317
TI  - Ideal body image and health status in low-income Pacific Islanders.
AB  - Purpose of this descriptive study was to examine the relationship between ideal
      body image and family support in Pacific Islander. The subjects were 120
      residences (65 with diabetes and 55 without diabetes) of a housing project in
      Hawaii. Data were collected by interview using the following questionnaires: The
      Family Behavior Checklist, the Modified Body Image Questionnaire, the Diabetes
      Knowledge Scale, and demography. Variables of primary interest included the
      subjects' ideal body image, serum level of glycosylated hemoglobin, hypertension,
      family support behaviors, ethnicity, and knowledge of diabetes. Findings
      indicated that the majority of subjects perceived receiving family support in the
      diet regimen, but not in the areas of glucose self-monitoring, exercise, or
      medication. The subjects' knowledge level regarding diabetes scored low. Subjects
      perceived that families lacked knowledge of diabetes. Metabolic control
      significantly correlated with present age, sources of health insurance, presence
      of diabetes, and the feeling of ideal body image according to non-Western
      culture. Subjects had different standards of ideal body image depending on
      whether they identified with a Western culture or with a non-Western culture.
      CONCLUSIONS: Presence of hypertension and diabetes were associated multiple
      environmental factors (e.g. family support, knowledge of diabetes and number of
      children per household) as well as cultural value (e.g. ideal body image).
      Findings provide diabetes educators with information regarding the ideal body
      image among low-income Pacific Islanders. It implies the importance of assessing
      the individual's perceptions of ideal body image according to his or her cultural
      values prior to developing regimens for diabetes or hypertension.

PMID- 12046318
TI  - Birth spacing initiative in Oman.
AB  - The Sultanate of Oman, faced with the potential for a population explosion that
      would drain national educational and economic resources, has initiated a birth
      spacing program which is in its fifth year of implementation at all Ministry of
      Health facilities. The program was developed based on data from a survey of
      married Omani women of childbearing age and their spouses. Success has been
      attributed to the inclusion of Muslim religious leaders at all stages of planning
      and implementation to deflect people's concern that child spacing is forbidden,
      and to educational outreach to men.

PMID- 12046319
TI  - Health beliefs and practices in rural El Salvador: an ethnographic study.
AB  - OBJECTIVE: To investigate the health practices and lifeways of rural villagers in
      a remote area of El Salvador who had been displaced by the recent civil war. The
      purpose of the study was to explore their view on health and experiences of loss
      during the war. DESIGN: Ethnography (Spradley, 1980, 1999; Agar, 1996). METHOD:
      The participants included any resident of three rural Salvadoran villages who
      were 18 years of age and over. Participants included nine families, with a total
      of twelve participants. Data collection included participant observation,
      audiotaped interviews, demographic information, and field notes. One of the
      Spanish-speaking key informants acted as the interpreter. The content of all data
      was analyzed for recurrent themes. FINDINGS: All nine families were displaced to
      refugee camps in Honduras during the civil war. Two cultural themes that emerged
      from the data were: 1) War: "We lost everything; we had to leave running," and 2)
      Health: "It's in God's hands." CONCLUSIONS: It is a challenge to encourage
      culture-specific care that acknowledges Salvadoran herbal remedies, strength of
      spirit, and a belief that a Supreme Being controls their lives. The health
      practices of the participants were shaped by their experiences of suffering from
      loss of family members during the war, displacement from their homes, and lack of
      potable water and environmental sanitation. IMPLICATIONS: To make a positive
      impact and effect change on health services in these rural areas, efforts should
      be directed toward democratic and community-based social and economic development
      within the context of the cultural system. Recent earthquakes (2001) have
      intensified the need for improvement in environmental factors including potable
      water.

PMID- 12046320
TI  - [Diagnosis and treatment of paretic forms of lumbar osteochondrosis].
AB  - This study was based on the analysis of the results of examination and treatment
      of 85 patients with lumbar osteochondrosis with paretic disturbances. The degrees
      of neurological disorders were analyzed by distributing these patients into three
      groups including patients with monoradicular, polyradicular motor disorders and
      circulatory disturbances in the caudal portions of the spinal cord. The
      informative value of the performed techniques (X-ray study, MRI, myelography,
      myelography with computed tomography, electroneuromyography) and the necessity of
      their combination for increasing the quality of diagnosis were determined.
      Criteria for choosing this or that treatment were defined. Indications for
      surgery, the time of its performance, and its efficiency were investigated.
      Surgical outcomes were analyzed by the groups of patients. The paper shows it
      necessary to use metallic fixing devices in some cases in order to stabilize an
      altered segment degeneratively, which allows improve the outcome of a surgical
      intervention. Postoperative rehabilitative treatment is also outlined.

PMID- 12046321
TI  - [Temporary sacral and tibial neuromodulation in treating patients with overactive
      urinary bladder].
AB  - The effects of temporary sacral (S3) stimulation and posterior tibial nerve
      stimulation were studied in patients with the overactive urinary bladder.
      Unilateral temporal (10 days) electrical stimulation of the S3 sacral spinal
      nerve (32 patients) and posterior tibial nerve stimulation (18 patients) were
      used to treat this abnormality. There was a decrease in the average frequency of
      voiding, in the number of leakage episodes and used pads per day after both
      stimulations. An over 50% symptomatic improvement was achieved in 19 of the 32
      patients and after temporary sacral (S3) stimulation and in 14 of the patients
      following posterior tibial nerve stimulation. Neuromodulation is an effective
      treatment in patients with the overactive bladder.

PMID- 12046322
TI  - [Surgery for hyperostotic cranial orbital meningiomas].
AB  - The paper analyzes surgical techniques for removal of hyperostotic cranial
      orbital meningiomas in 36 patients operated on in 1998 to 2000. In 19 cases
      hyperostosis extends to the upper and lower lid slits without involving the optic
      canal. It also spreads to the ethmoidal sinus in 6 cases to the frontal sinus in
      3, and to the maxillary one in 2 patients. In 3 patients, hyperostosis was beyond
      the wing of the basic bone, by involving the temporal and frontal squamous. In 19
      cases, hyperostosis was resected and the tumor was removed without creating any
      additional bone flaps. To make an additional basal bone flap can provide a much
      wider access by reducing the traction of both orbital and cerebral tissues. An
      orbitozygomatic flap was formed in 16 cases. To create a lateral orbital flap was
      sufficient to effectively eliminate hyperostosis in 3 patients. Impaired
      postoperative visual acuity was observed in 5 patients undergone resection for
      the hyperostotic optic canal, in 2 patients of them there was a decrease in
      visual acuity from 1.0 to 0.1 and in 1 patient it reduced from 1.0 to 0.2. A year
      later, visual acuity in these patients increased up to 0.5-0.8. After resection
      of the hyperostotic optic canal, blindness occurred in 2 patients, in one of
      them, photoperception appeared on day 5 after surgery and 3 months later visual
      acuity restored up to 0.6. Thus, the use of high-speed drill and the creation of
      an orbital or orbitozygomatic flap can increase the efficiency of removal of
      hyperostotic cranial orbital meningiomas.

PMID- 12046323
TI  - [Radical surgery for removing a malignant tumor of the temporal bone with extra-
      and intracranial involvement].
AB  - The paper presents a clinical case of combined therapy for adenocystic carcinoma
      of the petrous pyramid. The basic stages of treatment were preoperative
      radiation, tumor block resection, and postoperative radiation therapy. Based on
      the discussion of data available in the literature and on the case presented,
      practical guidelines for treatment policy are given. Such basic guidelines are as
      follows:--a lingering drug-unresponsible inflammatory process may be a
      manifestation of cancer diseases;--if there are clinical and diagnostic signs of
      neoformation, biopsy of a tumor (tissue under suspicion) is the basic premedical
      measure;--treatment policy combines different methods of multimodality treatment,
      but if there is an epithelial tumor, treatment should be started with radio-
      and/or chemotherapy.

PMID- 12046324
TI  - [Transcutaneous external ventriculostomy (surgical technique)].
AB  - The paper deals with the placement of external ventricular drainage, one of the
      most common mini-invasive surgical techniques. The operation is described in the
      stepwise fashion. Photos of each of the surgical stages allow the reader to gain
      a deep insight into the specific features of the surgical technique. This
      technique can be useful particularly for emergency neurosurgeons.

PMID- 12046325
TI  - [Endoscopic endonasal diagnosis and treatment of basal liquorrhea and
      encephalocele of the anterior regions of the skull base].
AB  - Endoscopic endonasal plastic repair of cerebrospinal-fluid fistulas and
      meningocele of the anterior regions of the skull base is an effective and
      miniinvasive procedure as compared with transcranial interventions. Endoscopic
      techniques may be used to close skull base defects in the nasofrontal pocket,
      ethmoidal infundibulum, cribriform lamina, sphenoid sinus. Limitations on the use
      of this procedure are cases of a fistula located within the posterior wall of the
      frontal sinus, within the lateral wall of the large sphenoid sinus, huge or
      multiple posttraumatic defects of the skull bases, as well as a combination of
      liquorrhea basalis and acute brain injury. According to latest papers, the
      successful outcome of endoscopic plastic repair ranges from 86 to 97%.

PMID- 12046326
TI  - [Some aspects of drug- and radiation-resistance of malignant brain tumors].

PMID- 12046327
TI  - [Modern aspects of spinal surgery].

PMID- 12046328
TI  - [Complex MR-diagnosis of brain abscesses].
AB  - Early diagnosis of brain inflammatory lesion is a basic factor in choosing
      treatment policy. The paper investigates the use and informative value of diffuse
      weighed magnetic resonance imaging in the differential diagnosis of brain
      abscesses and processes of another origin. It also considers the application of
      MR spectroscopy and perfusion MRI to obtain additional information on an
      inflammatory processes. A series of observations covered 10 patients with brain
      abscesses at different sites. Diffusion-weighed image (DWI) revealed a drastic
      increase in a MR signal from the central abscess portions (a pyonecrotic area),
      which is suggestive of decreased diffusion of water molecules. The measured
      diffusion ratios (MDRs) were significantly lower in the central abscess area (p <
      0.005) than those in the capsule and white matter of the brain at all values of
      the diffuse factor b (500, 1000 sec/mm2); the capsule was better visualized at
      the DWI at b = 500 sec/mm2. In addition, MDRs were significantly different within
      the annular contrasting area of abscesses and glioblastomas, in the
      abscess/tissue capsule, and edema (p < 0.01). Proton spectroscopy of the central
      abscess area (pus) revealed succinate, acetate, alanine, peaks of lactate and
      amino acid. Perfusion MR study (bolus contrasting and estimation of the tissue
      parameters rCBV and MTT) has indicated that the central abscess in relation to
      the medulla is a decreased perfusion area; perfusion in the abscess capsule is
      close to that in the medulla in its characteristics, but medullary time in this
      area is shorter than that in brain tissues; perifocal edema is also characterized
      by hypoperfusion. The analysis of complex MRI study in patients with brain
      abscesses has demonstrated that diffuse-weighed MRI enhances diagnostic
      specificity, diagnoses the development of a pyonecrotic abscess center at early
      stages of capsule formation; MR spectroscopy is an additional method of
      differential diagnosis of brain abscess and processes of another nature whereas
      perfusion MRI provides additional information on medullary hemodynamic changes.

PMID- 12046329
TI  - [From structural to functional genomics: theoretical and applied aspects].
AB  - The paper considers the results of studies of human genome and several eukariotic
      genomes, which have led to the establishment of the new genetic subject
      Structural Genomics and some other scientific areas. Particular attention is
      given to Proteomics considered to be the most developed section of Functional
      Genomics. The systems approach is ascertained to underlie proteomic strategy to
      study the protein products of gene expression with an ultimate goal of drawing up
      complete protein indices for definite organisms, such as proteomes, human
      proteomes in particular. The studies carried out at the Research Center of
      Medical Genetics, Russian Academy of Medical Sciences, have been used as an
      example to show that advances in Functional Genomics and the data of proteomic
      studies may be employed both for solution of theoretical problems and for
      different applied purposes (for development of diagnostic methods, for control of
      products derived from genetically modified plants, as well as during cellular
      therapy).

PMID- 12046330
TI  - [Mechanism of synergism of the sympathetic and parasympathetic nervous system in
      regulating cardiac and gastric activity].
AB  - The authors studied the mechanism of the higher vagus suppression of cardiac
      performance, which occurs when irritation of the sympathetic nerve is added to
      that of the vagus and when gastric motility occurring with the irritation of the
      sympathetic trunk is stimulated. Preganglionic serotonic fibers synaptically
      connected with serotoninergic intramural neurons are involved in showing these
      mechanisms.

PMID- 12046331
TI  - [Evaluation of microecology of colonic contents in patients with chronic
      pancreatitis].
AB  - The paper deals with microbiocenosis in the colonic content in 60 patients with
      chronic pancreatitis during its exacerbation. An analysis has indicated that in
      the colonic content there are the following microorganisms: Bifidobacterium sp.,
      10(8)-10(10) CFU/g; Lactobacillus sp., 10(1)-10(5) CFU/g; Escherichia coli, 10(8)
      10(10) CFU/g; Enterococcus faecalis, 10(6)-10(10) CFU/g; Enterococcus faecium,
      10(6)-10(10) CFU/g; the family Enterobacteriaceae (mainly Klebsiella-Enterobacter
      sp.), 10(1)-10(6) CFU/g; yeasty (including the Candida genus) and mold fungi,
      10(1)-10(5)/g; Staphylococci, 10(1)-10(3) CFU/g. Comparing the findings with
      those of normal cenosis according to different authors' data suggests that there
      are no apparently impairments in the levels of some microoranisms, the
      representives of microbiocenosis in the colonic content in the examinees.

PMID- 12046333
TI  - [Immunomodulators: principles for classification and strategy for use in
      medicine].

PMID- 12046332
TI  - [Medico-biological aspects of using stem cells].

PMID- 12046334
TI  - [Contractile action of the uterus in pregnancy. Biochemical mechanisms].

PMID- 12046335
TI  - [Professional osteopathies].

PMID- 12046336
TI  - [Diseases caused by varicella zoster virus: clinical appearance, frequency and
      treatment].

PMID- 12046338
TI  - [DNA methylation as an etiologic factor in carcinogenesis].
AB  - The paper presents current data on theepigenetic regulation of gene expression in
      malignant tumors. Methylation of CpG islands in the gene promoter regions not
      accompanied by DNA structural changes leads to gene inactivation. The analytical
      methods of DNA methylation are described in detail. Methylation of certain genes
      in different tumor types are examplified. Since methylation is an early marker of
      carcinogenesis, there is an opportunity of elaborating of prospective diagnostic
      protocols.

PMID- 12046339
TI  - [Usefulness of the saliva ferning test in diagnosis of Sjogren's syndrome].
AB  - One of the characteristics of mucous is its ability to crystallize to the form of
      ferns when it is dried at room temperature and observed by polarized light
      microscopy (ferning phenomenon-FP). Several studies have shown that dry mouth can
      be diagnosed on the basis the loss of FP in dried saliva samples. The aim of our
      study was to evaluate the value of saliva ferning test (SFT) in the diagnosis of
      Sjogren's syndrome (SS). Saliva was taken from 11 patients with primary SS, 32
      patients with secondary SS as well as from 27 controls. Samples of freshly
      produced saliva were dropped on light-microscope slides and allowed to dry at
      room temperature. Crystallization was observed by polarizing light microscopy
      within 10 minutes after collection. The type of crystallization was classified
      acc. to Rolando et al. Abnormal SFT was observed in 11 (100%) patients with
      primary SS and 27 (84%) patients with secondary SS. Saliva from 5 (16%) patients
      with secondary SS and from 27 (100%) control patients yielded normal picture of
      crystallization. In our opinion SFT is a simple, reproducible, and useful non
      invasive diagnostic test in SS.

PMID- 12046340
TI  - [QT dispersion and characteristics of left ventricular hypertrophy in primary
      hypertension].
AB  - The aim of the study was to evaluate the QT dispersion and the severity of
      arrhythmias in hypertensive patients according to the asymmetry of the left
      ventricular hypertrophy. The study group consisted of 47 hypertensive patients.
      In 24 of them the left ventricular hypertrophy was symmetrical (group I) and in
      23--asymmetrical (group II). For the evaluation of the left ventricular
      hypertrophy its thickness was analyzed in 13 segments. The ratio between the
      maximum and minimum thickness from any location was determined as the asymmetry
      index (AI). The value of this index 1,3 distinguished between patients with the
      symmetrical and asymmetrical left ventricular hypertrophy. 20 healthy subjects
      were examined as a control group (group III). All subjects underwent physical
      examination, the standard 12-lead electrocardiogram (ECG), twenty-four hour
      Holter recording and echocardiography. All the results for the QT dispersion
      (QTd, QTdc, QTdR) were highest in group II, lower in patients from group I and
      the lowest were observed in the control group. The differences in all parameters
      between group I and II were statistically significant: for QTd--V p < 0.01, QTdc-
      p < 0.05, QTdR--p < 0.05. The differences between groups II and III as well as I
      and III were statistically significant for all QT dispersion parameters: for QTd-
      p < 0.001 and p < 0.01 respectively, QTdc--p < 0.001, QTdR--p < 0.001 for both
      groups. We have observed a very distinct positive correlation between the
      asymmetry index and QTd, QTdc, QTdR (p < 0.001). These values correlated also,
      but less distinctly with the left ventricular mass index--LVMI (p < 0.05). The
      frequency and severity of ventricular ectopic beats did not differ significantly
      between group I and II. The results obtained indicate the lack of connection
      between the frequency of ventricular premature complexes and (1) all QT
      dispersion parameters, (2) LVMI, (3) AI. Supraventricular premature complexes
      occurred significantly more frequently in patients with the asymmetrical left
      ventricular hypertrophy compared to the group with the regular left ventricular
      hypertrophy (p < 0.05) and control group (p < 0.01). CONCLUSIONS: The left
      ventricular hypertrophy in primary hypertension may increase the QT dispersion.
      It seems that asymmetry of the left ventricular hypertrophy reinforces this
      increase. The increased QT dispersion in primary hypertension does not influence
      significantly the occurrence of ventricular arrhythmias.

PMID- 12046341
TI  - [Blood pressures values during evaluation of 24-h ambulatory blood pressure
      monitoring and left ventricular hypertrophy in patients with chronic renal
      failure treated with hemodialysis (HD)].
AB  - Left ventricular hypertrophy (LVH) is common and important predictor of risk of
      death in end-stage renal failure. In the present study we have analysed the
      relationship between 24-h ambulatory blood pressure (BP) profile and LVH. The
      effect of parathyroid hormone (PTH) on was also assessed. From a cohort of 85
      patients with crf we selected for analysis 59 stable patients. Ambulatory BP 24-h
      monitoring, echocardiography (ECHO), body mass index (BMI), serum creatinine,
      hemoglobin, total protein, albumin, electrolytes and PTH concentrations were
      assessed in all patients. Concentric LVH was detected by ECHO in 46 patients, in
      13 patients excentric LVH was observed. Mean 24-h ambulatory sBP, dBP, mean 24-h
      ambulatory day sBP, dBP as well as night sBP and dBP were significantly higher
      than in a control group 60 healthy subjects. It was a correlation between mean 24
      h ambulatory sBP and left ventricular mas (LVM) r = 0.606 (p < 0.0001), between
      mean dBP and (LVM) r = 0.498 (p < 0.001), between mean day sBP and (LVM) r =
      0.591 (p < 0.0001), between mean day dBP and (LVM) r = 0.479 (p < 0.001), between
      mean night dBP and (LVM) r = 0.548 (p < 0.0001), between left ventricular mass
      index (LVMI) and mean sBP r = 0.428 (p < 0.05), between LVMI and mean day sBP r =
      0.442 (p < 0.05). The loss in physiological night-time BP was observed in all
      patients. It was also correlations between PTH and (LVM) r = 0.704 (p < 0.001),
      and between BMI and LVMI r = -0.451 (p < 0.05). LVH is common in crf patients.
      These results confirmed that strong correlations between BP values and LVH and
      between serum PTH concentrations and LVH indicate that both hypertension and
      hyperparathyroidism play an important role in the LVH development.

PMID- 12046342
TI  - [Lamivudine in patients with chronic HBV infection and therapeutic difficulties].
AB  - AIMS: The primary objective of this study was to determine the efficacy and
      safety of lamivudine (LAM) therapy in patients with chronic HBV infection and
      contraindications to IFN therapy, nonresponders to IFN and patients with advanced
      liver fibrosis. PATIENTS AND METHODS: In this open study, 38 patients (25 men and
      13 women, age 19-68) with chronic hepatitis B virus infection (HBsAg, HBeAg and p
      DNA HBV positive) were treated with LAM (150 mg daily) for 48 weeks. All were
      negative for HCV or HDV coinfection and had no decompensated liver disease.
      Fourteen patients (group I) were nonresponders to IFN therapy, 15 patients (group
      II) had different contraindications for IFN therapy (e.g. depression, low number
      of neutrophils and/or platelets), and 9 (group III) had advanced liver fibrosis
      (staging = 3 or 4 [Knodell]). In all cases ALT activity was at least 2 times ULN
      before the therapy. After discontinuation of therapy all patients were followed
      up for another 36 weeks. RESULTS: During first 8-12 weeks of therapy rapid
      inhibition of HBV replication (p-DNA negativization) was noticed in all cases. At
      the end of therapy seroconversion to anti-HBe was observed in 24 cases (63%): 9
      patients (64%), 10 (67%) and 5 (55.5%) from groups I, II and III, respectively.
      In one case elimination of HBsAg and appearance of anti-HBs was observed.
      Sustained normalization of ALT activity was noticed in 22 patients (58%): 9 cases
      (64%) in group I, 8 (53%) in group II and 5 (55.5%) in III, respectively. During
      24 weeks of follow-up in 4 cases (17%) reseroconversion to HBeAg with reapperance
      of p-DNA activity was observed. ALT activity in these cases was slightly elevated
      but without clinical signs of exacerbation. In no case serious side effects were
      observed. CONCLUSIONS: The results indicate that monotherapy with lamivudine (150
      mg daily) for 48 weeks induces sustained inhibition of viral replication and
      normalisation of transminases in majority of patients with chronic HBV infection
      who did not respond to IFN, had contraindications to IFN therapy, and in those
      who had advanced liver fibrosis. The absence of side effects during lamivudine
      therapy is of special importance especially in patients with advanced liver
      fibrosis.

PMID- 12046343
TI  - [Computer analysis system for scintigraphic imaging of the thyroid in patients
      with hyperthyroidism treated with radioiodine].
AB  - Computerised system for analysis of radioiodine therapy efficiacy in hyperthyroid
      patients was presented. The system is based on comparative analysis of maximal
      emission distribution recorded in scintigrams performed before and after the
      treatment. It seems that the system after improvement of its software will be
      useful for clinical practice.

PMID- 12046344
TI  - [Complications of primary hyperthyroidism as a consequence of subsitutional
      therapy interruption].
AB  - The case of a 32-year old female patient with primary hypothyroidism suffering
      from severe myxoedema as a consequence of denying thyroxin taking is presented.
      Severe expression of pathological changes in circular-respiratory system and
      uncommon skin changes are discussed.

PMID- 12046346
TI  - [Does determination of troponin levels only have significance in patients with
      various forms of coronary heart disease?].

PMID- 12046345
TI  - [Skeletal changes during the course of pustulosis palmoplantaris--report of two
      cases].
AB  - We report two cases of coincidence palmoplantar pustulosis and joint changes. Two
      patients fulfilled criteria for arthroosteitis pustulosa: pustular eruptions of
      the palms and soles and pain of sterno-clavicular joint. They also fulfills
      criteria for SAPHO syndrome: osteoarticular manifestations of palmoplantar
      pustulosis. Clinical examination and scintigraphy confirmed the diagnoses.
      Treatment was started with antibiotics and nonsteroid anti-inflammatory drugs.
      Oral corticosteroids therapy with methotrexate was given to one patient.

PMID- 12046347
TI  - [Nitric oxide donors and their potentiating effects after botulinum toxin
      application for treatment of chronic anal fissure].
AB  - Pharmacological sphincterotomy with the use of botulinum toxin (BT) that inhibits
      acetylcholine secretion from neural endings in the motor plate or of nitric oxide
      (NO) donors should be a method applied earlier than surgical treatment due to its
      safety. BT mechanism of action on internal anal sphincter is not yet fully
      understood similarly to the effect of loosening of this sphincter under influence
      of NO donors applied after BT. Likewise paradoxical vasoconstrictive reaction on
      acetylcholine in the muscular layer of coronary arteries and decrease of tonic,
      vasodilative action of NO on the vessels may be observed in the patients with
      arterial hypertension. However, the muscle tissue of coronary arteries maintains
      the right dilative reaction on the endothelium independent NO donors. Local
      application of nitroglycerin is very safe and can be used by physicians in
      general practice for chronic anal fissure.

PMID- 12046348
TI  - [Relationship between SA gene Pst1 polymorphism and predisposition to H
      gestosis].
AB  - Genetic factors have been reported to play an important role in the
      predisposition to development of pregnancy-induced hypertension (PIH). On the
      other hand, there is strong evidence that genetic factors play important role in
      the predisposition to essential hypertension. Recently, the plausible "candidate
      gene" for the development of hypertension is SA gene. The aim of our study was to
      assess the association of the SA gene with the susceptibility to PIH. For that
      purpose, the SA gene A1A2 polymorphism was studied in 124 women (median age 28
      yrs) suffering from PIH in comparison with 148 healthy pregnant women (median age
      28 yrs). Genotyping was performed using methods based on polymerase chain
      reaction. In this study we found statistically significant more frequent of
      genotype A1A1 occurrence in the patients with PIH when compared to healthy
      pregnant controls. The frequency of A1 allele was also significant higher in PIH
      in comparison with controls (chi 2 test.) Based upon the results of our study we
      can suspect that the SA gene Pst1 polymorphism is associated with the
      predisposition to PIH in caucasian women.

PMID- 12046349
TI  - [Selective estrogen receptor modulators].

PMID- 12046350
TI  - [Inhibitors of HMG-CoA reductase in prevention of osteoporosis and bone
      fractures. Similar mechanism of action of statins and bisphosphonates].

PMID- 12046352
TI  - Psychosocial aspects of common skin diseases.

PMID- 12046351
TI  - [Molecular mechanisms influenced by parathyroid hormone on metabolism of bone
      tissue].

PMID- 12046353
TI  - Reforming primary care. Ending inertia but avoiding fatigue.

PMID- 12046354
TI  - Raloxifene remains an option.

PMID- 12046355
TI  - Aboriginal health and family physicians.

PMID- 12046356
TI  - Remuneration: looking for a better way.

PMID- 12046357
TI  - Remuneration: looking for a better way.

PMID- 12046358
TI  - Remuneration: looking for a better way.

PMID- 12046359
TI  - Remuneration: looking for a better way.

PMID- 12046360
TI  - Remuneration: looking for a better way.

PMID- 12046361
TI  - Remuneration: looking for a better way.

PMID- 12046362
TI  - Remuneration: looking for a better way.

PMID- 12046363
TI  - Use of warfarin during pregnancy.
AB  - QUESTION: One of my patients, who has been taking warfarin for some time for
      treatment and prophylaxis of deep vein thrombosis, became pregnant due to failed
      contraception. I am unsure how to counsel her. Is there evidence that warfarin
      use during pregnancy is associated with fetal risk? ANSWER: If possible, warfarin
      therapy should be avoided during pregnancy. If warfarin therapy is essential, it
      should be avoided at least during the first trimester (because of teratogenicity)
      and from about 2 to 4 weeks before delivery to reduce risk of hemorrhagic
      complications. Unfractionated heparin or low molecular weight heparin could be
      substituted when appropriate because these agents do not cross the placenta and
      are considered the anticoagulant drugs of choice during pregnancy.

PMID- 12046364
TI  - Dermacase. Georgraphic tongue.

PMID- 12046365
TI  - Practice tips. Cognitive-behavioural therapy in a family practice.

PMID- 12046366
TI  - Psychosocial effect of common skin diseases.
AB  - OBJECTIVE: To increase awareness of the psychosocial effect of acne, atopic
      dermatitis, and psoriasis. QUALITY OF EVIDENCE: A literature review was based on
      a MEDLINE search (1966 to 2000). Selected articles from the dermatologic and
      psychiatric literature, as well as other relevant medical journals, were reviewed
      and used as the basis for discussion of how skin disease affects patients' lives
      and of appropriate management. Studies in the medical literature provide mainly
      level III evidence predominantly based on descriptive studies and expert opinion.
      MAIN MESSAGE: Dermatologic problems can result in psychosocial effects that
      seriously affect patients' lives. More than a cosmetic nuisance, skin disease can
      produce anxiety, depression, and other psychological problems that affect
      patients' lives in ways comparable to arthritis or other disabling illnesses. An
      appreciation for the effects of sex, age, and location of lesions is important,
      as well as the bidirectional relationship between skin disease and psychological
      distress. This review focuses on the effects of three common skin diseases seen
      by family physicians: acne, atopic dermatitis, and psoriasis. CONCLUSION: How
      skin disease affects psychosocial well-being is underappreciated. Increased
      understanding of the psychiatric comorbidity associated with skin disease and a
      biopsychosocial approach to management will ultimately improve patients' lives.

PMID- 12046367
TI  - Rosacea and atopic dermatitis. Two common oculocutaneous disorders.
AB  - OBJECTIVE: To increase awareness of the oculocutaneous manifestations of two
      common skin diseases. QUALITY OF EVIDENCE: We reviewed clinically relevant
      articles from the dermatologic and ophthalmologic literature. The PubMed database
      was searched from January 1965 to January 2001 to locate retrospective and
      prospective cohort and descriptive studies using the MeSH terms acne rosacea;
      eczema; and dermatitis, atopic. Most literature on the topic is based on
      descriptive research. MAIN MESSAGE: Several dermatologic problems are known to
      have ophthalmologic sequelae. Rosacea and atopic dermatitis are two common skin
      conditions that can have concomitant eye disease. Degrees of skin and eye disease
      vary; certain cases require specialty referral and other cases can be managed
      effectively by family physicians. CONCLUSION: Better appreciation of how rosacea
      and atopic dermatitis overlap with eye disease will result in more appropriate
      referrals and more comprehensive patient care.

PMID- 12046368
TI  - Community education on preterm birth. Does it change practice?
AB  - OBJECTIVE: To evaluate how well physicians and other prenatal care providers
      educate women about early recognition of and appropriate response to the signs
      and symptoms of preterm labour (PTL). To assess use of antenatal steroids for
      babies born at less than 34 weeks' gestation. DESIGN: Before-after study using a
      population-based approach. SETTING: Health care providers' offices, hospitals,
      and prenatal classes in Ottawa, Ont. PARTICIPANTS: Prenatal care providers, women
      in hospital after giving birth, prenatal class participants. INTERVENTIONS:
      Prenatal care providers received information and educational materials on PTL and
      preterm birth (PTB). They passed this information on to pregnant women at their
      18- to 20-week prenatal visits. Teachers of prenatal classes gave the same
      information in early-series classes. Clinical practice guidelines were developed,
      and hospital staff received education on appropriate response to PTL. MAIN
      OUTCOME MEASURES: Use of educational materials and steroid treatment. RESULTS:
      Statistically significant increases were seen in the numbers of care providers
      who had educational material about PTL and PTB, who reported giving the
      educational material to all women, and who reported discussing signs and symptoms
      of PTL and PTB with all women; women who reported that their care providers
      talked with them about PTL and PTB, and women delivering preterm (< 34 weeks)
      babies who received steroids. CONCLUSION: Providing knowledge and standardized
      educational materials to health care providers can help improve preventive
      practice for PTL and educate women about PTL.

PMID- 12046369
TI  - Dissemination of discharge summaries. Not reaching follow-up physicians.
AB  - OBJECTIVE: To discover how often hospital discharge summaries were available to
      physicians seeing patients for follow-up visits after hospitalization. DESIGN:
      Cohort study. SETTING: Teaching hospital in Ottawa, Ont. PARTICIPANTS: We studied
      792 patients discharged from an internal medicine service after treatment for
      acute illness. We determined when and by which physician each patient was seen
      during the first 6 months after discharge. We also determined the date each
      patient's discharge summary was printed and the physicians to whom it was sent.
      We confirmed that summaries were received by means of a survey or by telephoning
      physicians' offices. Patients were observed for 6 months or until they were
      readmitted to hospital. MAIN OUTCOME MEASURES: Proportion of follow-up visits to
      physicians for which discharge summaries were available. RESULTS: During the
      observation period, patients made 6619 visits (median six per patient,
      interquartile range [IQR] 2 to 9) to 914 different physicians (median three per
      patient, IQR 2 to 4). Discharge summaries were available for only 996 (15%)
      visits. Summaries were available for only 65 initial visits (8.2%); no summaries
      were available for any visit for 542 (68.4%) patients. Summaries were most
      commonly unavailable because they were not generated in time for follow-up visits
      (20.0%) or were not sent to follow-up physicians (50.8%). CONCLUSION: At our
      institution, discharge summaries often did not get to physicians seeing patients
      after discharge from hospital.

PMID- 12046370
TI  - Short report: preparing for simulated office orals. Survey of practices in 16
      family medicine departments.

PMID- 12046371
TI  - Number of births to maintain competence.

PMID- 12046372
TI  - Drug databases for users of hand-held computers.

PMID- 12046373
TI  - "Don't tread on me". Why would you go into family medicine?

PMID- 12046374
TI  - Stressful results.

PMID- 12046375
TI  - Legible charts! Experiences in converting to electronic medical records.

PMID- 12046376
TI  - Bonanza for drug companies. Quebec's public drug plan pays for biotechnology
      boom.

PMID- 12046377
TI  - [Chronic ischemic disease of the digestive system].
AB  - The group of 236 patients with the clinical pattern of chronic ischemic disease
      of digestive organs (CIDDO) is examined. It is detected that the course of CIDDO
      is characterized by localization, character of affection and degree of blood
      circulation disorders in unpaired visceral arteries and can be represented by 6
      clinical variants. The erosive-ulcerous type of CIDDO was most frequently
      presented in male. It was combined with ischemic heart disease and
      atherosclerotic affection of arteries of lower extremities. In female the CIDDO
      more often flows as pseudo-pancreatic variant on a background of hypertension,
      dislipoproteidemia and hypothyroidism. It is proposed functional classes of
      disease on which the treatment strategy depends.

PMID- 12046378
TI  - [Clinical and morphological characteristics of ulcer in elderly patients].

PMID- 12046379
TI  - [Functional and morphological characteristics of the gastric mucosa in
      duodenogastric reflux].
AB  - In patients with the chronic gastritis in a combination with opisthorchiasis and
      with duodenogastric reflux it was marked the more expressed endoscopic and
      histological changes of stomach mucosa in comparison with the patients without
      reflux. In the patients with chronic gastritis and DGR the small colonization
      degree of mucosa by H. pylori was marked. The combination of endoscopic and
      histological changes in stomach mucosa at DGR allows to recommend the endoscopy
      as the basic method in clinical practice.

PMID- 12046380
TI  - [Dyspepsia and its treatment].

PMID- 12046382
TI  - [III Congress of the Scientific Society of Russian Gastroenterologists and XXIX
      Scientific Session of the Central Research Institute of Gastroenterology of the
      Moscow Health Committee].

PMID- 12046381
TI  - [The gastric mucigenous function in the treatment of patients with ulcer with
      various antisecretory preparations].
AB  - The investigation of the gastric mucigenous function in dynamics in the treatment
      by antisecretory medications was carried out in 120 patients with peptic ulcer
      disease. The selective Mi-cholinolytic gastrocepine, H2-blockers--Ranitidin and
      Famotidin, the proton pump inhibitor--Omeprasol, were used in the complex
      therapy. The mucigenous stomach function was investigated by the biochemical
      method at the level of sialic acids fractions, glycoproteins, glycosaminoglycans
      and proteins. It was shown that at the exacerbation of the ulcerative disease the
      expressed changes in gastric mucus were observed. It was shown, that Mi
      cholinolytic gastrocepine has the most effective recovering activity on the
      gastric mucigenous function. The obtained results expand the possibilities of
      differential use of antisecretory preparations in ulcerative disease in
      connection with the gastric mucigenous function and acidity disorders.

PMID- 12046383
TI  - [Treatment of patients with ulcer associated with Helicobacter pylori (experience
      with a triple therapy regimen].
AB  - The design of the medicamental treatment of the patients with duodenal ulcer
      disease associated with Helicobacter pylori is presented. It allows, as it was
      shown by our investigations, quickly to eliminate the pain in pyloroduodenal and
      (or) in epigastric areas and to achieve an adhesion of duodenal bulb ulcers
      according to the research protocol in 6 weeks. The eradication of Helicobacter
      pylori on the data of the fast urease test was determined in 9 of 10 patients.
      For getting more complete information about possibilities of using the given
      design of the medicamental preparations in the treatment of patients with
      duodenal ulcer disease associated with Helicobacter pylori, it is expedient to
      continue investigations in great numbers of the examined and treated patients.

PMID- 12046384
TI  - [Inhibitors of proton pump in the treatment of non-ulcer functional dyspepsia of
      the reflux-like type].
AB  - The results of two treatment types of the patients with chronic gastritis and
      with non-ulcerative functional dyspepsia (NFD) at reflux-similar variant are
      represented. The patients received Omeprasol (Losec) or Rabeprasol (Pariet)
      accordingly 20 mg once per day in the morning, 30-60 minutes before the
      breakfast. The treatment course was 7 days. The investigations have shown the
      following: the level of acidity has decreased in all the patients treated by
      Rabeprasol, normal acidity is detected in the all 15 patients, the level of
      gastric acidity has decreased in the patients, treated by Omeprasol. However the
      hyperacidity was preserved in 10 from 12 patients.

PMID- 12046385
TI  - [Non-ulcer dyspepsia syndrome].

PMID- 12046386
TI  - [Regeneration of the esophagus epitheliocytes. Evaluation of pariet efficacy in
      the treatment of patients with reflux esophagitis].
AB  - In this paper the information of treatment by Pariet (Rabeprasol) in 20 patients
      with erosive reflux-esophagitis are represented. On the basis of clinico
      endoscopic, morphological and immunohistochemical investigations it was shown,
      that using Pariet in treatment of the patients with erosive esophagitis the
      clinical-endoscopic remission, the regression of inflammation and apoptosis
      processes and proliferative epithelial activity is achieved in more short terms.
      The results of observation allow to recommend Pariet as a high effective
      preparation for treatment of the patients with gastroesophagities reflux.

PMID- 12046387
TI  - [Efficacy of the one week treatment with esomeprazole (nexium), clarythromycin,
      and amoxycillin of duodenal ulcer associated with Helicobacter pylori].
AB  - The results of one-week eradication therapy of uncomplicated duodenal ulcer
      disease associated with Helicobacter pylori by Ezomeprasol, Clarithromycin and
      Amoxicillin (accordingly 20 mg, 500 mg and 1000 mg twice per day) are presented.
      The results of the adhesion of uncomplicated ulcers of duodenal bulb in 4 weeks
      after termination of eradication treatment course--the adhesion of the ulcers was
      observed in 17 of 19 patients (89.5%). The eradication of Helicobacter pylori
      according the data of fast urease test and 13C-urease respiratory test was
      determined in all 19 patients (100%), on the data of histological method--in 18
      of 19 patients (94.7%).

PMID- 12046388
TI  - [Syndrome of malabsorption and the liver (a literature review)].
AB  - In this review the main clinico-laboratory and morphological changes of a liver
      in the patients with the syndrome of suction disorder are shown on an example of
      the patients with celiac disease and the short bowel syndrome (SBS). The data on
      recognition of symptoms of liver affections in this groups of the patients are
      presented. The expediency of correction of the liver pathological changes in the
      patients with celiac and SBS is discussed.

PMID- 12046389
TI  - [Changes in local humoral immunity during stomach ulcer healing with laser and
      drug therapy].
AB  - The increase of the contents of serum IgA, IgG, IgM on the edge of long non
      cicatrizing gastric ulcer was determined. At the same time the level of SIgA
      decreased in comparison with unaltered gastric mucosa. It is shown that the
      immunoglobulin content in the healed ulcer cicatrice depended on treatment
      method. The medicamentous therapy was accompanied by lowering of the contents of
      IgG, IgA, SIgA and by some increase of IgM level. The laser therapy is
      characterized by lowering of IgA, IgG, IgM level on a background of significant
      increase of SIgA content. The local humoral immunity after laser therapy was the
      same as in persons with unaltered gastric mucosa.

PMID- 12046390
TI  - [Metabolism pathways and use of heptral in chronic liver diseases].
AB  - Heptral (Ademetionine) plays one of the main functions in the intermediate
      metabolism, takes part in the processes of methylation and transulfurization and
      aminopropylation. The use of Heptral in patients with chronic liver diseases with
      accompanying holystase and encephalopathy of different degree, at depressions,
      related to alcohol and toxic liver disorders, is pathogenically reasoned for
      prevention of liver encephalopathy.

PMID- 12046391
TI  - [Antibiotic use and toxicity in liver diseases].

PMID- 12046392
TI  - [Xanthogranulomatous cholecystitis (a literature review and an own case report)].

PMID- 12046393
TI  - [A choice of optimal vegetotropic pharmacotherapy in patients with chronic non
      calculous cholecystitis in combination with dyskinesia of the gallbladder].
AB  - The group of 117 patients (58 male and 57 female, age from 17 to 54) with chronic
      non-calculous cholecystitis was examined. The control group included 54
      practically healthy persons. The motor-evacuation function of gallbladder was
      estimated on dynamic ultrasonographic findings of biliary system sorbet. The
      character of the autonomic regulation was determined on the basis of variability
      parameters of the heart rhythm. The results of the repeated dynamic
      ultrasonography of biliary system with sorbet on a background of vegetotropic
      medications (Atropine, Propranolol, Metoclopramide) have demonstrated that the
      variability parameters of heart rhythm can be used for an estimation of the
      autonomic regulation type and can become the basis of vegetotropic
      pharmacotherapy choice for the patients with chronic non-calculous cholecystitis
      and biliary dyskinesia.

PMID- 12046394
TI  - [Age characteristics of the bile duct system functioning in the norm and in the
      gastrointestinal system pathology].
AB  - At the present the age-specific particularities of many organs and systems used
      in diagnostics are determined. The function--morphological state of the biliary
      system in different age groups is poorly studied. The age-specific
      particularities of biligenesis in norm (control group--90 persons) and in
      pathology were studied by the following traditional methods: multifractional
      chromatic duodenal catheterization, dynamic scintigraphy of gallbladder, dynamic
      ultrasonic cholecystography. There were 167 patients with gastroduodenal diseases
      (chronic gastritis, gastric, duodenal and intestinal ulcers) and 115 patients
      with calculous cholecystites and chronic hepatites. The gastroduodenal affections
      reinforced the appearnce and the course of typical age alterations of biliary
      system. Patients sufferin from hepatobiliary pathology over 5 years biliation
      ability has remained in normal values.

PMID- 12046395
TI  - [Current etiological and pathogenetic mechanisms of the commissure formation in
      abdomen].

PMID- 12046396
TI  - [Syndrome of cavernous transformation of the vein portae ( a literature review)].
AB  - The literary data on the poorly investigated syndrome of cavernoma of the portal
      vein resulting to portal hypertension is represented. Inherent and acquired forms
      have described. The mechanisms of cavernoma development, clinical manifestations,
      diagnostic methods have represented. The problems of the differential diagnostics
      and treatment have considered in detail.

PMID- 12046397
TI  - [Absorption function of the large intestine in patients with nonspecific
      ulcerative colitis].
AB  - Colon absorption function was examined in twenty fife patients with active non
      specific ulcerative colitis (15 persons with the distal form and 10 with left
      side form investigate by rectal antipyrin test. The state of absorption was
      estimated on duration of antipyrin half-absorption, on attainment of its maximal
      concentration and on level of its salivary concentration. Most of patients (n =
      19) with active non-specific ulcerative colitis had disorders of colon
      absorption. This was demonstrated by reduced antipyrin absorption and decreasing
      amount of absorbed material. But in 6 patients with expressed destructive
      inflammatory processes the antipyrin absorption was intensified. In patients with
      ulcerative colitis the disorders of colon antipyrin absorption depend on activity
      of inflammatory processes.

PMID- 12046398
TI  - [The role of hereditary factors in etiology of chronic duodenitis and duodenal
      ulcer].

PMID- 12046400
TI  - Caries has increased dramatically in recent years, particularly among preschool
      children.

PMID- 12046399
TI  - [Protective effect of a zeolite enterosorbent in fluorine intoxication].
AB  - THE PURPOSE: To reveal the structural basis of protective influence of the
      natural ceolite enterosorbents in fluorine intoxication. METHODS: Fluorine effect
      was realized by exposure of 15 rats of Vistar's line in electrolysis shops of an
      aluminium plant. 15 animals were in normal ecological conditions and consisted
      the control group. The both groups received the natural ceolite. In the all rats
      the hysto-stereo-metric structure of intestinal mucosa has studied. RESULTS: The
      use of ceolite promoted to decrease of necrosis volume and to increase of immune
      and extrasecretory structure activity in experimental animals after fluorine
      effect. THE CONCLUSION: The possibility of ceolite enterosorbent use is
      substantiated as protective means lowering the toxic fluorine effects.

PMID- 12046401
TI  - Radiographic diagnosis: how do our minds work?

PMID- 12046402
TI  - The use of x-ray film by dental professionals in the United States.

PMID- 12046403
TI  - Dental digital radiography.
AB  - Digital images offer tremendous advantages to dentistry in terms of the potential
      for lower exposure to patients, absence of darkroom or processing problems,
      convenience of image enhancement techniques and capacity for remote
      teledentistry. Digital systems are now able to acquire all types of images
      including panoramic and cephalometric. As technology continues to improve they
      may ultimately replace film as the medium of choice for dental imaging.

PMID- 12046404
TI  - The history of dental radiology.

PMID- 12046405
TI  - Image analysis of intraoral radiographs.

PMID- 12046406
TI  - The application of computed tomography to implant placement and evaluation--a
      technical note.

PMID- 12046407
TI  - Oral and maxillofacial pathology case of the month. Granulomatous (foreign-body)
      gingivitis.

PMID- 12046409
TI  - Child abuse and neglect: detection and reporting behaviors of Oklahoma dentists.

PMID- 12046410
TI  - Forewarned is forearmed: preventing practice breakdown.

PMID- 12046408
TI  - When seconds count: saving cardiac arrest victims with Automated External
      Defibrillators (AEDs).

PMID- 12046411
TI  - The great leap forward.

PMID- 12046412
TI  - Opening doors.

PMID- 12046413
TI  - How much could you earn overseas?

PMID- 12046414
TI  - Matron takes the helm.

PMID- 12046415
TI  - Work out your frustration.

PMID- 12046416
TI  - Home truths.

PMID- 12046417
TI  - Physiological observations of patients admitted from A&E.
AB  - BACKGROUND: A&E department records were collected over a four-week period for all
      patients admitted to hospital via A&E. Timing and values of recorded observations
      were collected, as was the length of time spent in the department. During the
      study period, 739 patients were admitted. Observation charts were available for
      728. Those having some observations within 15 minutes of arrival totalled 640 (88
      per cent); 378 (52 per cent) had temperature, heart rate, respiratory rate and
      blood pressure recorded; and 265 (36 per cent) had repeat observations while
      waiting for admission. The mean time in the department was three hours 43
      minutes. CONCLUSION: Recorded patient observations are carried out in an
      inconsistent pattern in this A&E department and standards should be set. Patients
      at risk of deterioration must be identified early. Complete observations should
      be carried out so that patients with abnormal physiology can be prioritized for
      treatment and repeated observation can be instituted to monitor response to
      interventions. Further work is needed to determine variables that provide the
      best prediction of outcome and whether increasing observation frequency and
      earlier activation improves outcome.

PMID- 12046418
TI  - Body adornment: piercings and tattoos.
AB  - Body adornment through tattoos and piercings is on the increase, making adverse
      side effects more common. Practitioners should be prepared to give advice, either
      before the event, or post-procedure in written and oral forms. The aim of this
      article is to inform practitioners of the sites and types of piercings, likely
      adverse side effects and estimated healing times.

PMID- 12046419
TI  - Physiology of the skin.
AB  - Knowledge of the anatomy and physiology of the skin, and its major roles in
      thermo-regulation, protection, vitamin D metabolism and control of blood pressure
      can assist nurses in assessment of skin conditions and general physiological
      disturbances. The protective roles of the skin are emphasised in discussion about
      skin cancers and the use of transdermal drug delivery mechanisms.

PMID- 12046424
TI  - [Complex plasty of the atrioventricular valve in defects with a functional single
      ventricle--surgical technic and midterm results].
AB  - Congenital heart diseases with a functionally single ventricle can be surgically
      treated using total cavopulmonary connection. Regurgitation of atrioventricular
      valves represents one of risk factors for death and unfavourable long-term result
      after this operation. During 1996-2001 total cavopulmonary connection with a
      complex plastic repair of atrioventricular valves was performed in 8 patients at
      the age from 1.4 to 13.3 years (median 7.8 years). All patients had very complex
      congenital heart diseases with severe malformation of atrioventricular valves.
      All but one had pulmonary stenosis or atresia. Six patients had common
      atrioventricular orifice, 5 patients had bilateral superior caval veins and 4
      patients had dextrocardia or mesocardia. In 6 (75%) patients one or two
      palliative operations had been performed earlier. Before surgery all patients
      were cyanotic with severe hypoxemia and polyglobulia. All patients had
      regurgitant atrioventricular valves. The surgery was performed from the midline
      sternotomy approach, in extracorporeal circulation and moderate hypothermia. The
      surgery consisted in excision of the atrial septum, construction of a direct
      connection of all superior and inferior caval veins with the pulmonary artery,
      transsection of the pulmonary trunk and complex plastic repair of
      atrioventricular valves. The inferior caval vein was derived to the pulmonary
      artery using an intraatrial lateral tunnel in 3 patients and using an external
      conduit from a Goretex vascular prosthesis in 5 patients. In 5 patients a
      fenestration in tunnel or conduit permitting decompression of the systemic venous
      return was done. Individualized plastic repair of atrioventricular valves
      consisted in the suture of the central portions of both common leaflets. Four
      patients required also commissuroplasty of one to four commissures and two
      patients required annuloplasty. All patients survived the early postoperative
      period. In the majority of them complications occurred: hypoxemia in 3, pleural
      effusions in 3, low cardiac output in 2 and bleeding in 1 patient. In two
      patients reintervention for severe hypoxemia was necessary. Postoperative
      echocardiographic examination proved good result in all patients. In 6 (75%)
      patients the grade of regurgitation of atrioventricular valves decreased
      immediately after the repair, in the two remaining patients the degree of
      regurgitation decreased during the follow up. One patient with the most severe
      residual regurgitation which progressed during the follow up died 2.5 years later
      under the signs of congestive heart failure after spontaneous closure of
      fenestration. The 7 (87.5%) living patients remain in good clinical condition in
      NYHA class I or II. Our experience proved that it is possible to perform total
      cavopulmonary connection with low mortality and good midterm results even in
      patients with hemodynamically significant regurgitation of atrioventricular
      valves. Persistent severe or progressive regurgitation, however, requires
      surgical reintervention.

PMID- 12046425
TI  - [Traumatic rupture of the diaphragm in blunt injuries].
AB  - The authors present a group of 12 casualties operated on account of a traumatic
      rupture of the diaphragm. The rupture of the diaphragm was part of an associated
      thoracoabdominal injury or multiple injury. The casualties were examined within
      the framework of the diagnostic algorithm, in 11 of them rupture of the diaphragm
      was proved by spiral computed tomography. The diaphragm was injured in 7 subjects
      on the left and in 5 on the right. In 8 casualties during injury of the diaphragm
      also a serious intrathoracic injury was treated (in 5 laceration of the lungs)
      and of intraabdominal organs (in 4 laceration of the liver and in 2 laceration of
      the spleen). On the left side injuries of the diaphragm were always treated from
      laparotomy, on the right in 4 patients from thoracotomy. In 4 patients with
      concurrent injury of the intrathoracic and intraabdominal organs a
      thoracoabdominal approach was selected. During the postoperative period one
      female patient with multiple injuries died. The cause of death was contusion of
      the brain. According to the authors' experience it is useful to apply for early
      diagnosis of diaphragmatic injuries modern non-invasive imaging methods (spiral
      post-contrast computed tomography). The surgical approach depends on the presence
      of associated intrathoracic and intraabdominal injuries. The therapeutic results
      are limited by the presence of serious associated injuries.

PMID- 12046426
TI  - [Conversion of laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy is nowadays the method of choice in treatment of
      symptomatic cholecystolithiasis, despite the fact that some operations cannot be
      completed laparoscopically and are converted. In a group of 431 patients operated
      during the last two years the authors evaluate the causes and predispositions of
      conversion which was performed in 7.4%. A significantly higher risk was found in
      subjects above 65 years of age, in those with ultrasonographic signs of
      thickening of the gallbladder wall and patients with acute cholecystitis. The
      risk of conversion is not significantly influenced by the patient's sex, obesity,
      the condition after endoscopic retrograde cholangiopancreaticography,
      pancreatitis and a previous abdominal operation.

PMID- 12046427
TI  - [Results of surgical treatment of gastric cancer].
AB  - The authors retrospectively analyse a group (1991-2000) of 129 patients with
      malignancies of the stomach operated at the Surgical Department of The District
      Hospital in Lucenec. The operated patients were: males 83 (64%), females 46
      (36%), mean age--63.4 years. Elective operations were performed in 78.2% and
      acute operations in 21.8%. We were able to make resections in 90 (69.8%) patients
      and palliative operations in 39 (30.2%) patients. On the basis of histologic
      examinations-adenocarcinomas dominated (120 patients--93%). The postoperative
      mortality was 4.65% and five-year survival 12%.

PMID- 12046428
TI  - [Indications for percutaneous endoscopic gastrostomy in patients with disorders
      of the nervous system].
AB  - Percutaneous endoscopic gastrostomy (PEG) is an efficient endoscopic method that
      ensures enteral nutrition for a longer period of time in patients who cannot take
      food per os. This method is also indicated in patients suffering from disorders
      of the central or peripheral nervous system which developed suddenly, such as a
      stroke or craniocerebral injuries, or gradually, such as amyotrophic lateral
      sclerosis (ALS), dementia, and multiple sclerosis. It has become common practice
      in the cooperation between neurologists and a gastroenterologists to use PEG in
      patients hospitalized in a neurological ward with encephalomalacy and
      haemorrhage, or craniocerebral injuries (after the patient recovers from the
      acute stage of the disease and is transferred to a neurological ICU), as well as
      in patients with ALS in a progressive stage. We gradually extend the indications
      of PEG for other patients with neurological disorders such as patients suffering
      from dementia, progressive multiple sclerosis, Parkinson's disease, and
      progressive polyneuropathy. Of 62 patients hospitalized in a neurological ward
      during a period of 4.5 years, 56 patients suffered from sudden disorders of the
      nervous system (strokes and craniocerebral injuries) and 6 patients had gradually
      progressing neurological diseases (ALS, multiple sclerosis, Parkinson's disease,
      dementia, and polyneuropathy).

PMID- 12046429
TI  - [Simultaneous bezoars in the stomach, ileum and cecum causing acute ileus in a 30
      year-old imbecile--case report].
AB  - Bezoars are concretions of foreign materials in the stomach, small intestine or
      bowel in people or animals, which impair GIT motility or cause intestinal
      obstruction. The authors describe an interesting case report of a 30-year-old
      imbecile with manifestation of simultaneous bezoar of stomach, ileum and caecum
      and its operative treatment. They describe a short characteristics of this
      clinical unit, which is reported in the literature only in a few case reports.

PMID- 12046430
TI  - [Carcinoma of the stomach and regional metastases].
AB  - The authors analyze a group of 39 patients with gastric cancer in different
      thirds of the stomach in relation to the incidence of regional nodal metastases
      and the preoperative evaluation of the proximal and distal resection line. They
      recommend lymphadenectomy of all three nodal compartments as they are regularly
      affected with metastases, and mandatory preoperative microscopic examination of
      the resection lines.

PMID- 12046431
TI  - [Bouveret's syndrome: biliary ileus manifested by acute upper gastrointestinal
      hemorrhage and impaired gastric emptying].
AB  - The authors present a very rare case of impaired gastric evacuation, known as
      Bouveret's syndrome, caused by a large biliary concrement wedged in the duodenum
      as a result of the development of a cholecystoduodenal fistula in a 77-year-old
      man. The condition was manifested clinically by developed high ileus and
      subsequent haemorrhage into the upper GIT. The diagnosis was established on the
      background of the clinical picture, passage through the upper GIT and endoscopy.
      As the attempt to remove the concrement endoscopically failed, laparotomy had to
      be used. In the conclusion of this case-record the authors discuss the method of
      assessment of the correct diagnosis endoscopically and possibilities of
      therapeutic strategy.

PMID- 12046432
TI  - [Complications of endoscopic extraction of foreign bodies and their treatment].
AB  - Endoscopic extraction of foreign bodies from the upper part of the digestive
      tract has become recently the method of choice. As this method can be associated
      with very serious complications which cannot be resolved endoscopically and which
      may have permanent sequelae, it is important to consider the indication of
      endoscopic extraction of foreign bodies from the oesophagus or stomach very
      carefully. Fore illustration the authors present the case of a young female
      patient who swallowed by mistake a fork During its extraction a serious injury of
      the oesophagus occurred which had to be treated surgically. In the discussion
      pros and cons of endoscopic extraction are considered, the main principle being
      primum non nocere.

PMID- 12046434
TI  - ["Nursing patients: society and we"].

PMID- 12046433
TI  - [Regional biochemical and hematologic changes in patients after revascularization
      of the lower extremities in ischemia of the extremities].
AB  - INTRODUCTION: Surgical treatment of PAOD is related to iatrogenic ischaemia
      caused by arterial clamping and ischaemia which is result of natural development
      of the disease. The pathway of skeletal muscle reperfusion injury is complex and
      one of the most important factors related to injury is endothelial damage. The
      expected reason of endothelial damage is increased production of oxygen free
      radicals by prematurely activated PMN (polymorphonuclear) leukocytes (direct
      injury). Non-specific tissue injury is related to releasing of PMN elastase.
      Endothelial dysfunction, hypercoagulable state and microcirculation stasis are
      responsible for indirect injury and no-reflow fenomena. STUDY DESIGN:
      Observational pilot study. METHODS: 10 patients underwent surgery because of PAOD
      (all suffering from critical limb ischaemia). During reperfusion period in
      defined intervals following parameters were measured (samples were taken from
      ipsilateral femoral vein): PMN elastase, lactate, total antioxidant status,
      malondialdehyd, minerals, acid-base balance, blood count, APTT, prothrombin time,
      fibrinogen and HTI (heparin tolerance index). RESULTS: Patients with PAOD are
      threatened by hypercoagulable state with its clinical and surgical consequences.
      Maximal grade of local acidosis is reached 2 hours from the beginning of
      reperfusion. Tissue damage is expressed by maximum activity of PMN elastase 18-24
      hours during reperfusion and represents non-specific tissue damage. Low total
      antioxidant status reveals high sensibility to oxygen free radicals. MDA does not
      achieve the pathological range in observed series. CONCLUSION: Our results
      confirmed inevitable importance of prevention of hypercoagulability, oxygen free
      radical tissue damage and PMN elastase activation to avoid of non-specific tissue
      damage.

PMID- 12046435
TI  - [Families need help. Family midwife--the Bremen model and experiences].

PMID- 12046436
TI  - [Poverty causes illness. WHO favors the family health nurse as a means for
      controlling the sequelae of poverty].

PMID- 12046437
TI  - [Family caregivers. New study finds that nurses can support these families].

PMID- 12046438
TI  - [Brain jogging. Brain training within the scope of health promotion].

PMID- 12046440
TI  - [Holistic nursing with healing touch. Experiences with an energy healing method].

PMID- 12046439
TI  - [Is there an absolute protection of Life? Bioethics concepts lexicon. 2: From E
      K].

PMID- 12046441
TI  - [Rehabilitation nursing. Thoughts on a new specialty field].

PMID- 12046442
TI  - ["The Kaiser's new clothes"].

PMID- 12046443
TI  - [Learning capacity of acute stroke patients. A pilot study].
AB  - INTRODUCTION: Acute stroke patients find themselves in a new and totally altered
      health situation. Several factors add to its complexity. In order to master the
      health situation as independently as possible, patients must possess the
      appropriate knowledge. In turn, they must be able to learn. The aim of this study
      was to answer the question, to which extent will acute stroke patients be able to
      attain and recall health related and rehabilitation related information. The
      hypotheses were, that acute stroke patients do possess the ability but that their
      performance differs, depending on the localization of the lesion and from the
      performance of non-stroke patients. METHOD: A convenience sample resulted in 12
      participants with hemispheric infarct, eight participants with lacunar infarct
      and nine participants in a comparison group. By means of structured interview the
      level of knowledge of all participants was asked, followed by structured teaching
      and the same structured interview. Five days later the structured interview was
      carried out again. RESULTS: The results show that acute stroke patients are able
      to attain and recall the information offered. Different performance related to
      the region of lesion and to non-stroke patients could not be proved. CONCLUSIONS:
      The ability of acute stroke patients as demonstrated here represents a resource
      for their rehabilitation during the acute phase. The method and content of
      structured teaching prevents occasional and inconsistent knowledge transfer. The
      specific information needs of these patients may not be left disregarded. The
      information needs of significant others must be taken into account as well.
      Further research is needed, to lighten up the learning behavior of acute stroke
      patients and to prove the effect of structured teaching for this group of
      patients.

PMID- 12046444
TI  - [Nursing personnel in inpatient rehabilitation--work satisfaction, motivation for
      interdisciplinary cooperation and for achieving psychosocial competence].
AB  - 106 nurses from eleven rehabilitation clinics were questioned by means of an
      anonymous clinical questionnaire on the issues of job satisfaction,
      interdisciplinary cooperation, and expectations towards future psychosocial staff
      training (main fields of the participants: orthopaedics, cardiology, dermatology
      and neurology). Two thirds were altogether satisfied with their jobs, primarily
      with regard to their relationships with the patients and the colleague nurses
      (76%), to some extent less so, however, with the doctors (63%). More than 90%
      expected psychosocial service to deliver feedback for the team and close
      interdisciplinary communication. Main expectations of psychosocial staff focused
      on the improvement of communication skills with strained patients, on improved
      psychological and especially psychodiagnostic knowledge as well as more
      functional coping with conflicts with patients and team-members (60% expressed
      marked expectations with regard to each issue). More than half of the staff
      indicated that they would prefer regular training sessions of one to two hours'
      duration, and more than 20% favoured each one-day- or weekend-workshops. The most
      popular ways of working in staff training were "discussion of team conflicts",
      "exchange of experience", "seeking emotional release", "discussing cases" and
      "training of communication skills" (approx. 60% each). Nearly 90% found "coping
      with aggressive patients" as well as "depression and suicide" to be the most
      important issues, followed by "ways of self-protection", "dealing with anxious
      patients", "coping with illness", "improvement of team-atmosphere" and "coping
      with death and dying". The findings of the study recommend an integration of
      psychosocial issues into education--and training--curricula for the various
      professions in rehabilitation.

PMID- 12046446
TI  - [Nursing discharge planning: from the viewpoint of patients and necessary
      consequences for hospital organization].
AB  - As the length of time that patients stay in hospital becomes shorter,
      transitional nursing care will become even more important as one of the concepts
      of integrated medical care. This means that in Germany, in the years to come, the
      viewpoint of those receiving this care--i.e. the patients and those closely
      involved with them--will also become increasingly important. The success of
      concepts relating to transitional nursing care will depend on how satisfied the
      patients are and how well they cope with living at home again after their stay in
      hospital. This article will focus on the sight of patients who received
      transitional nursing care and describe a evaluation study in Nuremberg/Germany.
      It is becoming clear that, in order to remain successful in the long term,
      concepts concerning transitional care will always additionally involve consistent
      measures in relation to organisational and staff development.

PMID- 12046445
TI  - [Nursing performance on specialty units, hospital departments and for patient
      groups--a comparison based on minimal nursing care data].
AB  - Nursing in Germany hides behind structural data like quantity and costs of
      nursing staff. This must be changed in aspect of the transparency of services in
      hospitals. The aim of this pilot study is to describe nursing services, find main
      focuses of nursing and point out significant differences between field units,
      wards and patient groups. On the basis of Belgian Nursing-Data-Sets, which was
      modified, all in all 2347 inpatient-days of 550 patients were collected.
      Analogous to the Belgian action, a Ridit Analysis was conducted, which allowed
      the construction of nursing profiles for every desired aggregation level. The
      knowledge of experience available regarding the different nursing services in
      departments and on the stations can at least be made valid, possibly even revised
      with the existing data equipment for the participating clinic. The easy to handle
      minimal Nursing Data Set allows the creation of a data basis, that can support
      decisions regarding the allocation of financial and personnel resources.

PMID- 12046447
TI  - [Case report of a granulosa-theca tumor in a cow].
AB  - A 2 year-old cow with abnormal behaviour was observed during a farm visit. Rectal
      palpation of the cow revealed the presence of a mass of at least 12 cm in
      diameter. After further examination, it appeared that 'ovarian tumour' was the
      most likely differential diagnosis. In order to confirm this diagnosis, blood
      samples were drawn and analysed for plasma progesterone and plasma oestradiol-17
      beta concentrations. Also, the gross pathology and histology of the mass were
      evaluated. The combination of the clinical presentation of the cow, the hormone
      concentrations, and the histological appearance of the mass confirmed the
      diagnosis ovarian tumour. The tumour was classified as granulosa-theca cell
      tumour.

PMID- 12046448
TI  - [Playing God? Critical consideration of biotechnology].
AB  - The ethics must do justice to the man who can freely decide and should pose to
      him the proper questions that can lead to a good choice. 'Playing God' is out of
      the question, because the biblical God has taken the enchantment out of the
      creation and produced man for him to shape and keep her. The zygote is already a
      human being in gestation. But not all stages of gestation of man have the right
      to the same reverence. The end justifies the means. Reason why this growing
      respect should be weighed against the use and meaning of the modifying action.
      The goal should be human in order to have a justifiable effect. Man is not
      determined by his genes but conditioned by them: they are pliable. Prenatal
      diagnostic tests and cloning should not be allowed to lead to the moulding of an
      'Ubermensch'. It is indeed not yet technologically possible. Germination
      technology is justifiable provided that it is safely performed. DNA-profiling for
      identification of criminals is allowed. If only the profile and not the DNA were
      kept one could consider making a profile-bank. The patenting of discoveries
      should not stop developing countries from getting cheap medicines (e.g. for
      AIDS). Not everything that is possible is also allowed. Every time the reason and
      the benefit should be weighed against the damage and there must be a humane
      authority.

PMID- 12046449
TI  - [Inbreeding].

PMID- 12046450
TI  - [Resigned minister Laurens Jan Brinkhorst: "For a total preventive vaccine
      policy, majority rule is unattainable." (Interview by Cathelijne Cras)].

PMID- 12046451
TI  - [Interview with Frits Pluimers. CVO concerning foot and mouth disease control:
      "Large initiatives in the making." (Interview by Sophie Deleu)].

PMID- 12046452
TI  - [Inflammatory bowel disease (IBD): development in the area of diagnosis and
      treatment].

PMID- 12046453
TI  - [Veterinary drug advice commission: medicated feeders with or without A, D, and J
      additives].

PMID- 12046454
TI  - [Arrangement for standardized form concerning special emergency slaughter].

PMID- 12046455
TI  - [Legislation for horses--artificial insemination].

PMID- 12046456
TI  - [Prohibition of four dog breeds seems definite].

PMID- 12046457
TI  - [Circovirus type 2 widely spread in the Dutch pig husbandry].

PMID- 12046458
TI  - [More and more veterinarians are sick. Personal attention in work disability is
      crucial].

PMID- 12046459
TI  - [Spectrum of antibodies to HCV antigens in patients with different clinical
      patterns of chronic HCV infection].
AB  - Correlations between the spectra of antibodies to HCV proteins represented by
      various antigenic determinants and clinical variants of chronic HCV infection
      were studied. Synthetic peptides core-16, NS4-20, and NS5-23 simulating the
      immunodominant regions of the core, NS4 and NS5 proteins and recombinant proteins
      core-114 and NS4-86 were used as antigens. The results indicate that if the serum
      of an HCV patients contains no IgG to both antigenic determinants of NS4 or to
      NS5 in combination with any core antigenic determinant, a clinical and
      biochemical remission is highly probable. Chronic hepatitis C is characterized by
      the presence of IgG in high titers to both antigenic determinants of NS4 protein,
      particularly in combination with anti-NS5 IgG in low titers or none at all, or
      high titers of anti-core-16 IgG in combination with high titers of anti-NS4-20
      IgG.

PMID- 12046460
TI  - [Procoagulant activity of blood cells in pestivirus infection].
AB  - An increased level of procoagulant activity (PCA) in leukocytes of pigs with
      acute classical swine fever (CSF) was observed on day 4 postinfection; PCA level
      normalized during the moribund state. CSF vaccine strain either did not induce an
      increase of PCA level or induced an increase that persisted for at least 11 days.
      Time course of PCA changes in the leukocytes from sheep infected with borderline
      sheep disease was similar to the time course of PCA in acute CSF. In vitro each
      of the pestiviruses induced an increase in PCA in homologous and heterologous
      leukocytes.

PMID- 12046461
TI  - [Propagation of hepatitis E virus in an endemic and nonendemic regions].
AB  - The role of hepatitis E (HE) in sporadic morbidity at an endemic territory
      (Southern Uzbekistan) and the incidence of anti-HEV in different populations of a
      nonendemic region (Russia) were evaluated. Antibodies to HEV were detected in
      22.1% of patients with acute HE, including mixed infections (+ HA or HB), in the
      Dekhkanabad district of Kashkadarya region in 1993. The estimated incidence of
      acute HE was 51.7 per 100,000 population. Analysis of monthly incidence of acute
      HE demonstrated a seasonal pattern of the morbidity: more than 80% of total
      recorded cases occurred in August-September. These data indicate the presence of
      group HEV infections and an important role of this infection in the structure of
      acute viral hepatitis at the endemic territory. Anti-HEV were found in some
      population groups at a nonendemic territory: in free-of-charge blood donors in
      Surgut (4%), in patients with HIV infection (1.6%), and in medical workers in
      Moscow (1.1%).

PMID- 12046462
TI  - [Changes in phospholipid components of pulmonary surfactant in experimental
      influenza infection and their correction by remantadin and deitiforine].
AB  - Changes in the levels of total phospholipids and phospholipid fractions of
      pulmonary surfactant fractions of albino mice intranasally infected with
      influenza A/Aichi/2/68(H3N2) virus in a dose of 5 LD50 were studied. Reproduction
      of influenza virus in mice is paralleled by fluctuations in the level of total
      lipids and changes in the phospholipid components of pulmonary surfactant.
      Antiviral drugs remantadin and deitiforine injected in accordance with the
      treatment and prophylaxis protocol to infected animals exerted a protective
      effect as regards the studied pulmonary surfactant phospholipids.

PMID- 12046463
TI  - [Construction and study of antigenic characteristics of recombinant salmonella
      strain producing TBI protein].
AB  - A recombinant strain producing TBI protein (artificial protein containing HIV-1 B
      and T cell epitopes) was constructed on the base of attenuated Salmonella
      typhimurium SL7207 strain and BALB/c mice were immunized with this strain in a
      dose of 10(9) live cells orally or rectally. A single immunization with the
      recombinant salmonella strain induced humoral and cellular immune response to HIV
      1; hence, this strain is a promising candidate for vaccine against HIV.

PMID- 12046464
TI  - [Immunogenic and protective characteristics of recombinant Lassa virus NP
      protein].
AB  - Recombinant fragment of Lassa virus (strain Josiah) nucleocapsid protein
      (corresponding to amino acid residues 141 + 569) constructed by Dr. Jan ter
      Meulen (Tropenmedizine, Hamburg) was used for immunizing CBA/calac mice. The
      preparation was injected intraperitoneally twice with 2-week interval in a dose
      of 10 micrograms. The parameters of the resultant specific humoral and cell
      mediated immunity were comparable to those in reference animals immunized with
      inactivated Lassa virus. Challenge with Lassa virus (10,000 PFU) resulted in 100%
      death of the reference animals, while of 15 animals immunized with the
      recombinant NP protein 8 survived.

PMID- 12046465
TI  - [Localization of tick-borne encephalitis virus protein E antigenic determinant
      recognized by antihemagglutinating monoclonal antibodies using a phage-display
      peptide library].
AB  - Bacteriophages bearing peptides reacting with antihemagglutinating monoclonal
      antibodies (MAb) 10H10 to tick-borne encephalitis (TBE) virus protein E were
      selected from a phage-display peptide library by affinity selection and enzyme
      immunoassay. The library contained randomized peptides that are 6 amino acids
      long, fused with protein pIII and exposed on the surface of the bacteriophage. No
      significant homology between the sequences of selected peptides and TBE virus
      protein E was detected. Computer software was created to locate the conformation
      epitopes on the surface of protein E. Amino acids R73, C74, T76, M77, N103, C105,
      L107, and S112 were found to form a discontinuous epitope recognized by MAb
      10H10. These amino acids are remote in the protein sequence but close in the
      tertiary structure and form a whole epitope located in the structural domain II
      of protein E. Presumably the localized amino acids bind to the cellular receptor
      for TBE virus.

PMID- 12046466
TI  - [Newly isolated mink parvovirus strain].
AB  - A new mink enteritis virus (MEV) strain, called Cherepanovo, was isolated in the
      Novosibirsk region (West Siberia). The level of this strain's accumulation in
      cell culture is lower than that of commercial MEV strains Rodniki or Beregovoi.
      Identification of Cherepanovo strain by hemagglutination inhibition test, protein
      electrophoresis in denaturing polyacrylamide gel, and PCR showed its similarity
      to the previously described MEV strains. Comparative analysis of this strain's 5'
      and 3' nucleotide sequences of VP2 gene showed its more than 98% homology with
      other feline parvoviruses. Nucleotide residues 2920, 2971, and 4245 in the
      Cherepanovo strain VP2 gene differed from those of all previously described MEV
      strains. It is noteworthy that transition at the position 4245 led to Phe-->Cys
      replacement in amino acid residue.

PMID- 12046467
TI  - [Hepatitis C virus RNA in patients with chronic hepatitis C].
AB  - Reviews recent data on the detection of genome and replicative HCV RNA in
      patients with chronic hepatitis C by PCR and in situ hybridization. Discusses the
      results of HCV RNA detection in the liver, lymphocytes, serum, and other organs
      and tissues and notes the relationship between the incidence of RNA and activity
      of the pathological process. Analyzes the results of HCV RNA detection after IFN
      treatment. Discusses the role of HCV RNA in the pathogenesis of hepatitis C.

PMID- 12046469
TI  - [Study of the effect of antiviral drugs on the reproduction of the respiratory
      syncytial virus by enzyme immunoassay].
AB  - A test system based on EIA was developed for evaluating the efficiency of drugs
      active towards the respiratory syncytial virus (RSV) in cell culture. Virasole
      and its structural analog ribamedii active towards RSV infection and arbidol
      whose activity in RSV infection is unknown were tested. Like virasole and
      ribamedil, arbidol inhibited the expression of RSV antigens, the inhibitory
      effect increasing with the drug concentration and decreased with increase of the
      multiplicity of virus infection. MIC50 for arbidol, virasole, and ribamedil were
      10, 5, and 6 micrograms/ml, respectively. These data prompt clinical trials of
      arbidol in RSV infection.

PMID- 12046468
TI  - [Relationship between interferon priming effect and functional activity of human
      blood cells].
AB  - Relationship between the priming effects of interferon (IFN)-alpha and -gamma and
      the standard IFN production by peripheral blood leukocytes was evaluated in 25
      volunteers (13 men and 12 women, mean age 35.3 years). Priming of IFN-alpha and
      IFN-gamma production positively correlated with the standard IFN-alpha and IFN
      gamma synthesis, respectively. On the other hand, primed production of IFN-alpha
      negatively correlated with that of IFN-gamma. Possible role of types I and II IFN
      interactions in the maintenance of physiological regulatory balance is discussed.

PMID- 12046470
TI  - [Sensitizing and virus-neutralizing characteristics of goat immunoglobulins to
      Ebola virus].
AB  - Sensitizing and virus-neutralizing properties of IgG isolated from the sera of
      goats immunized with Ebola virus and a relevant gammaglobulin prepared by ethanol
      fractionation were compared. The ratio of the virus-neutralizing activities of
      subclasses IgG2, IgG1a, and IgG1b was 100:10:1. Anaphylactogenic activity of IgG2
      in the immediate type hypersensitivity test in guinea pigs was 2-fold lower than
      that of IgG1a and IgG1b. Goat gammaglobulin to Ebola virus, consisting from IgG2
      antibodies by more than 50%, possessed virus-neutralizing and sensitizing
      characteristics compatible to IgG2.

PMID- 12046471
TI  - [Experimental results of using the "open lung concept"].
AB  - Several elements of the "open lung concept", like ventilation with small tidal
      volumes, were incorporated into various ventilatory strategies. Our study
      demonstrates how the whole concept can be applied in an animal model using a
      standardized protocol with the following possible results. Eighteen pigs weighing
      between 30 and 45 kg were anaesthetized, tracheotomized and ventilated. Acute
      lung injury was induced by surfactant washout. Blood gases were monitored via a
      continuous arterial sensor system (Trendcare system). After washout, the
      ventilatory pattern of the American "ARDS Network study" was applied (PEEP = 9
      cmH2O, volume controlled mode with a tidal volume of 6 ml/kg body weight and a
      respiratory rate of 25 breaths per minute). Afterwards, the opening pressure and
      the pressure at which the lung collapses were titrated. Both levels were used as
      the basis for adjusting the recruitment pressure and PEEP, which was necessary to
      keep the lung open. The respiratory rate was chosen in such a way that at a low
      intrapulmonary pressure difference between inspiration and expiration as well as
      normocapnia was reached. After induction of an acute lung injury by surfactant
      washout, the oxygenation index (OI) dropped from 556 +/- 54 to 176 +/- 89 mmHg.
      In the "ARDS Network" mode, OI increased to 285 +/- 49 mmHg. After alveolar
      recruitment with a peak pressure of 53 +/- 7 cmH2O and application of a median
      PEEP of 17 +/- 3 cmH2O, oxygenation returned close to baseline. A pCO2 of 33 +/-
      4 mmHg resulted after using a respiratory rate of 39 breaths per minute. The
      median tidal volume was 8 ml/kg body weight. Despite a short arterial systolic
      blood pressure drop of 23 +/- 11 mmHg during recruitment, no significant
      difference was detectable afterwards compared to the baseline. Using low tidal
      volumes alone, complete reopening was not achieved in an experimentally induced
      acute lung injury. After recruitment manoeuvres, it was possible to reopen the
      lung and keep it open by application of a sufficient PEEP.

PMID- 12046472
TI  - [Comparative studies of patient positioning for lumbar intervertebral disk
      operation].
AB  - For surgery on lumbar disks by the posterior route, patients are placed either on
      a Wilson frame or in genupectoral position. The aim of the prospective study was
      to record and describe the haemodynamic changes resulting from the patients'
      position. After written informed consent had been received, 80 neurosurgical
      patients undergoing lumbar disk surgery were randomly divided into two groups;
      group I--Wilson frame, group II--genupectoral position. In each group, 20
      patients received total intravenous anaesthesia (Alfentanil or Remifentanil,
      Propofol) and 20 balanced anaesthesia with Isoflurane and Alfentanil or
      Remifentanil. Haemodynamic parameters (mean arterial pressure--MAP and heart rate
      -HR) were recorded automatically at three measuring times (MT): firstly, after
      induction of anaesthesia; secondly, before re-direction; thirdly, after re
      direction on the Wilson frame or in the genupectoral position. Induction of
      anaesthesia did not lead to a significant decrease in MAP (MT 1: 92.5 +/- 15.2
      mmHg, MT 2: 89 +/- 13.4 mmHg, n = 80). In group I (n = 40), no significant
      changes were observed in MAP and HR at MT 3 (p = 0.882, p = 0.051). In comparison
      to group I, the genupectoral position was associated with significant drops in
      MAP and HR. The genupectoral position caused a significant decrease in MAP (p <
      0.001) and HR (p = 0.016) at MT 3. Our data suggest that body weight or body mass
      index do not necessarily lead to a preference for one of the two possible
      positions of the patient. Complications resulting from haemodynamic changes were
      not seen in either group. We recommend the Wilson frame for neurosurgical lumbar
      disk surgery in cases of cardiovascular or cerebrovascular disorders. The
      adaptive capacities in the genupectoral position as a result of the modifying
      distribution of blood volume are limited in these patients. Furthermore, the dose
      dependent effects of different anaesthetics on haemodynamic parameters in these
      prone positions should be explored.

PMID- 12046474
TI  - Implications of the Human Rights Act 1998.

PMID- 12046473
TI  - [Early contributions for the development of nitrous oxide-oxygen anesthesia in
      central Europe].
AB  - The American dentist Horace Wells was the first to administer nitrous oxide for
      pain relief during painful tooth extractions. Since, however, an official
      demonstration of the pain-relieving properties of the gas at Massachusetts
      General Hospital in Boston ended in failure, use of the drug was abandoned. A few
      years later, Gardner Quincey Colton, a former coworker of Wells, took up Wells'
      idea to use nitrous oxide for pain relief and this was instrumental in its
      reintroduction into daily practice. Colton's publications on the advantageous use
      of nitrous oxide caused Stanislav Klikovitch from St. Petersburg, Russia, to
      administer the drug for pain relief during labour. In order to minimize the risk
      of asphyxia during the inhalation of the gas, he used an anaesthetic mixture
      consisting of 80% nitrous oxide and 20% oxygen. Moreover, it is to Klikovitch
      that we owe the first description of effective self-administration of nitrous
      oxide mixtures for pain relief. He recommended that inhalation should start 30-60
      seconds before the expected pain and said between 2 and 6 inhalations would give
      the expected effect. Additionally, he suggested taking deep breaths and doing so
      at the beginning of subsequent pains. This is the first description of patient
      controlled analgesia. Klikovitch reported his experiences with the new
      anaesthetic method in several German-language publications. Among those who were
      fascinated by his pain-relieving concept was Paul Zweifel from Leipzig, one of
      the leading obstetricians of his time in Germany. Together with numerous of his
      pupils, he popularized the method, using new apparatus for a safer kind of
      administration. Further technical developments in the early twenties, such as the
      introduction of the circle system or the clinical use of oxygen-monitoring
      devices, were additional milestones in nitrous oxide/oxygen anaesthesia.

PMID- 12046475
TI  - Network on pain management.

PMID- 12046476
TI  - Sexual health workshops.

PMID- 12046477
TI  - Care co-ordination? The reality from a carer's perspective.

PMID- 12046478
TI  - Research priorities.

PMID- 12046479
TI  - Do children's nurses make a difference?

PMID- 12046480
TI  - Keep taking the tablets? Evidence-based approaches to AD(H)D. Part 2: Audit and
      changing practice.
AB  - The audit cycle was used to look at our practice in the light of new developments
      in the literature and the new evidence available to us. Using this new
      information we were able to refine our practice, set new standards and measure
      our practice against these new standards. This new information allowed us to
      further develop new ways of making our assessment and to implement this into our
      practice. We still need to continue the audit cycle by revisting the process, and
      auditing other parts of our service to children and young people diagnosed as
      having Attention Deficit (Hyperactivity) Disorder.

PMID- 12046481
TI  - The child first and always: the registered children's nurse over 150 years. Part
      One.

PMID- 12046482
TI  - 'Mental health should be tackled in secondary schools'. New mental health
      foundation initiatives.

PMID- 12046483
TI  - The importance of coordinating ostomy care and teaching across settings.

PMID- 12046484
TI  - No small potatoes: managing a complex wound with a stoma.

PMID- 12046485
TI  - Healing a wound with an exposed Herrington rod: a case study.

PMID- 12046486
TI  - Relieving pain during dressing changes in the elderly.

PMID- 12046487
TI  - Evaluating the effectiveness of a dressing for use in malodorous, exuding wounds.
AB  - Malodorous, exuding wounds can cause problems for patients in terms of discomfort
      and social isolation. A prospective, noncomparative, multicenter study was
      conducted to evaluate the effectiveness of an odor-controlling dressing in the
      management of patients with chronic and acute exuding, malodorous wounds. Forty
      six patients with various malodorous wounds (mean duration prior to study entry
      of 231.6 weeks) participated in the study. The majority of the patients were > 65
      years of age (mean 70.7 years). Wound characteristics, odor, and dressing exudate
      absorption were assessed at baseline and at every dressing change (total: 348
      dressing changes). Overall assessment of the dressing's ability was rated as good
      or excellent for odor control (91% of patients), exudate management (82%), and
      overall comfort (86%). Patient and nurse perception of odor were similar. While
      appropriate treatment to address the cause of exudate and wound odor remains a
      priority, the results of this study suggest that discomfort and isolation may be
      reduced through the use of odor-control dressings.

PMID- 12046488
TI  - A prospective, randomized, controlled double-blind study of a moisturizer for
      xerosis of the feet in patients with diabetes.
AB  - Xerosis is frequently noted in the feet of people with diabetes. The presence of
      xerosis increases the risk of complications, including infection and ulceration,
      making it imperative to counteract its effects. A prospective, randomized,
      controlled double-blind study was conducted to compare the efficacy of a test
      moisturizer containing 10% urea and 4% lactic acid versus its emulsion base
      vehicle in the treatment of xerosis of the feet in patients with diabetes. Forty
      patients (mean age 62 +/- 11 years) with diabetes and moderate-to-severe xerosis
      of both feet were enrolled. Xerosis severity was assessed using a nine-point
      Xerosis Assessment Scale. The tested moisturizer was applied to one foot and the
      vehicle to the other, twice a day, for 4 weeks. The regression of xerosis also
      was evaluated 2 weeks following discontinuation of the treatments. Progress was
      noted weekly with photographs and examination. Feet treated with the vehicle
      cream (control) had an initial mean xerosis grading of 6.17 (+/- 0.79) and a
      final xerosis grading of 4.38 (+/- 2.20). In the treatment group, mean xerosis
      grading diminished from 6.13 (+/- 0.73) to 3.19 (+/- 2.23) after 4 weeks (P <
      0.01). The difference between control and treatment remained statistically
      significant following discontinuation of cream application. In this study,
      regular use of a moisturizer was found to be beneficial in the treatment of
      moderate-to-severe xerosis of the feet in patients with diabetes. The cream
      containing 10% urea and 4% lactic acid provided faster and better improvement
      with significantly less xerosis regression.

PMID- 12046489
TI  - Managing wound pain in patients with vacuum-assisted closure devices.
AB  - The etiology and management of wound pain for patients with vacuum-assisted
      closure devices can be complex. Patients, such as the patient with necrotizing
      fasciitis described in this case study, may experience all three types of pain
      described in the Chronic Wound Pain Experience Model--acute noncyclic, acute
      cyclic, and chronic. Strategies that include local wound management to reduce all
      three types of pain and holistic psychological care to reduce the ache and
      anguish that may accompany dressing change procedures may help provide comfort
      and reduce pain and suffering.

PMID- 12046490
TI  - The health of home health care.

PMID- 12046491
TI  - Folic acid. Health Canada takes aim at neural tube defects.

PMID- 12046492
TI  - Screening for childhood speech-language problems.

PMID- 12046493
TI  - Community health. Sexuality and the mental health client.

PMID- 12046494
TI  - Cultural diversity. Recognizing discrimination in nursing practice.

PMID- 12046495
TI  - Prior learning assessment. Putting experience to the test.

PMID- 12046496
TI  - When a client considers surrogacy.
AB  - Although the registered nurse is not expected to have expert knowledge in all
      areas of practice, clients do ask questions in one health service area that might
      normally be handled in the context of another service area. When these sorts of
      'surprising questions' arise, it is important for registered nurses to determine
      the nature of the question and to provide as much beginning assistance and
      guidance as possible to help the client to clarify the issues/concerns. Clearly,
      the nurse should do all she can to assist Sarah to access nurses and other health
      professionals who could provide more complete information and counselling for
      Sarah.

PMID- 12046497
TI  - Nurses must recognize we're humans too.

PMID- 12046498
TI  - Working with physicians can make standardization reality. Merging perspectives.

PMID- 12046499
TI  - Green rover, come over. Hospital's environmental team efforts impact every
      department.

PMID- 12046500
TI  - Readying bioterrorism defenses. Preparations continue despite inadequate funds.

PMID- 12046501
TI  - [Relationship between the concentration of antibodies to myosin heavy chains in
      serum and symptomatic carotid atherosclerosis].
AB  - It is believed that atherosclerosis could result from inflammatory
      fibroproliferative response to various forms of injury of endothelium and smooth
      muscle cells of arterial wall. The aim of this study was to examine whether
      immunological reaction against myosin filaments of carotid artery (CA) wall
      smooth muscle cells is involved in atherogenesis. 43 patients (22 females) with
      first-ever ischaemic stroke proven by CT were investigated. The results were
      compared with those obtained in 40 (21 females) healthy sex- and age-matched
      subjects. Anti-myosin antibodies (AMA) were evaluated by solid phase
      radioimmunoassay using rabbit myosin heavy chains as an antigen. The intima-media
      thickness (IMT) of common and CA--a measure for atherosclerosis--was estimated
      with the use of high-resolution ultrasonography. The AMA serum concentration in
      stroke patients was significantly greater than in control subjects (p < 0.001).
      Mean IMT for CA in stroke patients was significantly increased compared with the
      controls (0.98 +/- 0.17 mm vs. 0.68 +/- 0.13 mm; p < 0.0001). There was a
      significant correlation between AMA serum antibodies concentration and IMT (r =
      0.51; p < 0.001). CONCLUSION: The significant correlation between AMA
      concentration and IMT of CA is the basis of the hypothesis that immunological
      reaction against myosin heavy chains of smooth muscle cells in CA is involved in
      atherogenesis.

PMID- 12046502
TI  - [Clinical and genetic study of juvenile form of Huntington's disease].
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by high instability and extension of CAG sequences within the coding
      region of IT15 gene. It affects both sexes and age at onset of the disease may be
      different but usually occurs in midlife. The term Juvenile Huntington's disease
      is generally applied to 10% of the cases with onset before 20. We present
      clinical features and results of DNA analysis in 16 patients from 14 families
      aged 9 to 36. The age of onset was between 5 to 20 years; duration of the disease
      was from 2 to 16 years. In 10 cases the mutated gene was transmitted by the
      affected father; only in two cases by the mother. In all cases anticipation
      manifested by earlier onset of the disease in subsequent generations and
      expansion of CAG repeats was documented. The number of CAG repeats was between 50
      and 92 (mean 67.3). Progressive mental deterioration, declining school
      performance, hyperactivity and emotional disturbances were the first symptoms of
      juvenile HD. Neuropsychological assessment showed mean IQ in Wechsler test 59.6
      and Mini-Mental State Examination scores 22.8. Rigidity and bradykinesia were
      predominant features in the cases with juvenile onset, the remaining ones
      developed choreatic movements. Three persons had epileptic seizures; two (both
      females) revealed behaviour and psychiatric disturbances. Amplitudes of
      somatosensory evoked potentials, visual evoked potentials and brainstem auditory
      evoked potentials were markedly reduced. MRI of the brain showed atrophy of heads
      of the caudate nuclei, putamen and globus pallidus.

PMID- 12046503
TI  - [Analysis of epileptic pregnant women delivering between 1992-1998 in obstetric
      departments of the University Medical School in Lublin].
AB  - Pregnancy in woman with epilepsy arouses several serious medical problems and
      always belongs to the group of high obstetric risks. The aim of the present
      clinical study was the evaluation of the antiepileptic treatment efficiency
      during pregnancy, including risk factor, effects on pregnancy and delivery in
      epileptic patients. The study group consisted of 84 epileptic pregnant women
      which delivered between 1992-1998 in Obstetric Departments of University Medical
      School of Lublin. A randomised group 80 healthy pregnant women constituted the
      control group. The mean age of the analysed patients was 25 years. 51 epileptic
      patients were pregnant for the first time, 23 patients for the second time and 10
      patients for the third time or more. The mean duration time of the disease was
      8.6 years. In our study group: 45 (53.8%) patients experienced primary
      generalized tonic-clonic seizures and 39 (46.6%) patients experienced partial
      seizures. 26 patients were treated with monotherapy and the rest with polytherapy
      methods. The estimation of the seizure frequency during pregnancy in 52 (61.9%)
      patients did not change, in 13 (15.4%) patients increased. Among obstetric
      complications: urinary tract infections, hypertonia (EPH-gestosis) were observed.
      In 4 newborn congenital defects have been noted. Mothers of three of them were
      treated with Phenydantin (heart lesion, developmental anomaly of fingers). The
      fourth mother used Convulex (meningoarachnided hernia, hydrocephalus).

PMID- 12046504
TI  - [Pain in the course of multiple sclerosis].
AB  - According to previous studies pain symptoms were a problem in multiple sclerosis
      (MS) patients. This is an important issue since symptom control, especially pain,
      assume high priorities in MS. The aim of study was to assess the incidence and
      type of pain symptoms in MS. In the study 104 consecutive patients with
      clinically definite MS, according to Posers criteria, were evaluated by
      questionnaire. In all patients brain MRI strongly suggested MS. 76% of patients
      had relapsing-remitting (RR) course of the disease. At any stage of the disease
      pain syndromes occurred in 70.2% of MS patients. In 8% patients pain was the
      first symptom of MS. The most common acute pain syndromes were: Lhermitte sign
      (26%) and painful tonic spasm (19%). The incidence of migraine was 8% and 26% had
      tension headache. Chronic pain occurred in 60% of MS patients. Most common were
      dysaesthetic extremity pain (45%), low back pain (34%) and painful leg spasm
      (22%). There was no correlation with age, sex, and duration of disease. Pain
      symptoms were more frequent in MS patients with higher EDSS score and spinal cord
      involvement. Pain syndromes are common in MS patients. There was no correlation
      with age, sex, and duration of the disease. Pain occurred more frequent in MS
      patients with higher EDSS score and in patients with spinal cord involvement.

PMID- 12046505
TI  - [Evaluation of surgical treatment results in extreme lateral lumbar disc
      prolapsed after 12 months of follow-up].
AB  - In 1988-1997, patients with extreme lateral disc prolaps (KBWJM) were operated on
      the Department of Neurosurgery Medical Academy of Bialystok. Females accounted
      for 4.9% (2 cases) and 95.1% were males (39 cases) with age range 41-60 years.
      During a study of clinical state 12 months after the operation, we found in 75.6%
      of patients good and very good results of the surgical treatment of KBWJM. During
      that period of time, two patients (4.9%) were reoperated out of 41 all patients.

PMID- 12046506
TI  - [Colloid cysts of the pituitary gland].
AB  - Colloid cysts of the pituitary gland are very rare pathological lesions occurring
      in sellar region. Their pathogenesis is not clear. They are located between the
      anterior and posterior lobe of the pituitary. Colloid cysts of the pituitary
      gland are space occupying lesions and induce hypopituitarism, diabetes insipidus,
      visual disturbances, etc. They cause pituitary apoplexy too. Magnetic resonance
      imaging is the preferred neurodiagnostic method in evaluating these lesions. 503
      transsphenoidal procedures were performed from January 1996 to February 2001.
      Hypothalamo-hypophyseal dysfunction was caused by colloid cyst in seven cases.
      The most frequent presenting symptoms were headaches, oligomenorrhea and loss of
      libido. Diabetes insipidus was found in two cases before surgery. Colloid cyst
      induced pituitary apoplexy in one patient. Two patients presented visual
      disturbances. All our patients were operated on. We performed six transsphenoidal
      procedures and one transcranial operation. Postoperatively, the endocrine
      function of the pituitary gland was evaluated. We concluded that transsphenoidal
      operation is a safe method for treating colloid cyst located in the sellar
      region.

PMID- 12046507
TI  - [Neuropsychological deficits after surgical repair of anterior communicating
      artery aneurysm].
AB  - Based on the review of literature we tried to establish the pattern and dynamic
      of psychoneurological disturbances as a result of rupture and surgical procedures
      of anterior communicating artery (ACoA) aneurysm in three aspects: pathoanatomy,
      pathophysiology and rehabilitation. Anterior communicating artery syndrome
      (amnesia, confabulation, personality changes) was observed in very few patients,
      especially in those after clipping of an anterior communicating artery
      (trapping). Mostly neuropsychological pattern consisted of anterograde memory
      problems, executive dysfunctions, global attention impairments, confabulations
      and personality changes. Neuropsychological deficits observed in ACoA patients
      were probably a result of basal forebrain lesions. The precise analysis of the
      disturbances is necessary especially in the early stage. Proper cognitive
      rehabilitation of attention and memory functions is recommended to improve
      professional and daily living activities.

PMID- 12046508
TI  - [Neuroprotective mechanisms of adenosine action on CNS neurons].
AB  - Adenosine is known to play a significant role as modulator of neuronal activity.
      Extracellular levels of adenosine increase during ischaemia. Adenosine has been
      reported to have beneficial effects against neurodegenerative diseases, although
      the mechanisms are not fully clarified. Adenosine A1 receptors are found on
      neurons and presumably involved in the regulation of the release of excitatory
      amino acids. Using adenosine kinase inhibitors and novel A1 agonists with potent
      CNS effects and diminished influence on the cardiovascular system offers
      therapeutic potential to the treatment of neurodegenerative brain disorders.
      Recently deleterious effects have been reported following the activation of A2A
      and A3 adenosine receptor subtypes. The selective A2A receptor antagonists have
      been demonstrated to markedly reduce cell death after brain ischaemia in the rat.
      This paper discusses the possible role of adenosine receptor subtypes and their
      agonists or antagonists in neurodegenerative diseases treatment.

PMID- 12046509
TI  - [Gait characteristics in hemiparetic patients after stroke].
AB  - The first and major criterion of success in broadly understood management of
      patients with stroke is to regain motor ability, at least minimally. It starts as
      early as possible with mobilisation of patients in bed, in a room or ward since
      the first days after stroke onset. Standing up and gait learning are subsequent,
      rapidly coming stages of rehabilitation that are of key importance in reaching
      the outcome of treatment, prevention of likely complications and change in the
      quality of life. However, reports on gait impairment have been mostly very brief
      and limited, and pathological gait of patients with hemiparesis has been thought
      to be merely "helicopod one". Physiological mechanisms of gait programming,
      following a focal brain lesion, impairment of gait steering and its clinical
      manifestation, and some practical suggestions of assessment and prognosis of gait
      impairment are presented in this article.

PMID- 12046511
TI  - [The first system of image transmission and neurosurgical telecommunication in
      Poland].
AB  - OBJECTIVE: The goal was to develop a fast and efficient neurosurgical
      teleconsulting network to improve acute neurosurgical patient care, to reduce
      transport costs and unnecessary occupation of neurosurgical beds. METHODS: Modems
      with 56 kilobits/s data transmission speed are used. CT images are transmitted
      straight from CT scanner via modem/telephone lines to receiving personal computer
      in Department of Neurosurgery. Receiving PC runs with Microsoft Windows operating
      system and the network software MultiView (EMED, Inc.). Network connects
      Department of Neurosurgery Polish Academy of Sciences in Warsaw with transmitting
      hospitals in Ciechanow and Ostroleka. RESULTS: The system is fast, one study
      consisting 18 images is transmitted in about 5 minutes and it is simple to use,
      to date more than 1000 CT images have been transmitted. Operator acceptance has
      been very high. The system has improved acute neurosurgical patient care.
      Transfer of appropriate patients has been accelerated and unnecessary transfer is
      almost eliminated. CONCLUSION: Applied Neurosurgical Teleconsulting System has
      significantly improved acute neurosurgical patient care and has reduced transport
      expenses. Better availability of neurosurgical consultation has been achieved.
      The network is simple to use and has gained physician acceptance. It has to be
      emphasized that the creation and using of the system is relatively not expensive.

PMID- 12046510
TI  - [Problems in the selection of surgical approach for the treatment of non
      traumatic deformities of the craniocervical junction].
AB  - Developmental abnormalities or inflammatory disorders provoke deformations and
      instability of the craniocervical junction. The most dangerous results of these
      lesions are: sudden brainstem compression or cervical myelopathy. The authors
      propose the guidelines for surgical management of non-traumatic deformities
      caused by: a) rheumatoid arthritis of the spine, b) congenital anatomic changes
      of the occipit and odontoid. Main goals of surgical treatment are decompression
      and stabilization. The choice of surgical approach and method depends on
      pathology. It is very important to estimate individual anatomic changes and
      mobility--possibility of reduction. The authors discuss surgical methods actually
      used for fusion and decompression of the occipitocervical junction.

PMID- 12046512
TI  - [A case of vascular malformation in vertebral artery region in a 12-year-old
      boy].
AB  - The authors present a case of cerebral vascular malformation in vertebral artery
      region which was found in 12-years old boy with hemiparesis.

PMID- 12046514
TI  - [Clinical course and evolution of lesion in MRI in central pontine myelinolysis
      in a patient abusing alcohol].
AB  - The authors report a 44-year-old patient with at least a 10-year history of
      alcohol abuse in whom an organic brain syndrome developed with cerebellar ataxia,
      left-side hemiparesis and bulbar symptoms. MR imaging of the head demonstrated a
      large hyperintense focus in T2-weighted images involving the central part of the
      pons. Central pontine myelinolysis was diagnosed. Laboratory investigations
      showed no hyponatraemia. After withdrawal treatment and motor function
      rehabilitation the neurological symptoms regressed nearly completely. After 18
      months control MR imaging demonstrated considerable reduction in the size of the
      myelinolysis area in the brainstem, despite the fact that the patient resumed
      alcohol drinking.

PMID- 12046513
TI  - [Extensive intracerebral calcifications in a patient with
      pseudohypoparathyroidism (Albright syndrome)].
AB  - The authors present a case of extensive symmetric intracerebral "calcification"
      in a patient with pseudohypoparathyroidism. Disproportion between extensive
      intracranial concrements in visual examination and poor symptomatology are
      discussed as well.

PMID- 12046515
TI  - [Vertebral canal abscess as a complication of congenital sacral sinus in a two
      year old girl].
AB  - Vertebral canal abscess is rather an uncommon disease. Since 1830, when the first
      report that spinal of abscess was published. Till to 2000, no more than 20 cases
      as a result of dermal sinus infection were reported. Dermal sinus results from an
      incomplete separation of the cutaneus ectoderm from the neural ectoderm between
      the 4 and 6 weeks of fetal development. Surgical excision of the sinus is the
      treatment of choice for prevention of infection. The authors describes a 2-year
      old girl with that abscess secondary to dorsal dermal sinus in sacral region. The
      patient presented with fever, since two weeks, flaccid paraparesis mainly in the
      right lower extremity, urinary and bowel incontinence. The child was initially
      treated conservatively, and after limitation of inflammatory process the dermal
      sinus and dermoid cyst containing a large quantity of pus were excised. The
      authors reviewed the literature of spinal cord abscesses secondary to congenital
      dermal sinus. The diagnostic and therapeutic methods presented in the literature
      are discussed in comparison with our case.

PMID- 12046516
TI  - [Posttraumatic visual agnosia and epilepsy as a consequence of gunshot injury to
      the head. Case report].
AB  - Half million people in the world, each year have a gunshot injury to the head and
      eighty thousand of them are hospitalized. Gunshot injuries to the head have
      became in Poland second most frequent cause of death from head trauma, and in
      some countries during peace became the most frequent cause of death among patient
      with head injury. Glasgow Coma Scale (GCS) is a useful prognostic factor for
      patients with gunshot injury to the head. Injury to the eloquent regions of the
      brain, commotion and contusion of the brain, intracranial hematomas, subarachnoid
      hemorrhage, cerebro-vascular spasm, injuries to the major vessels, liquorrhea,
      infections, coagulopathies and epilepsy are the most important and influential
      factors in the clinical status of the patient with gunshot injury to the head.
      The operation is the preferred treatment to all patient, no matter of their
      clinical status at the moment of the admission. The report presents the history
      of treatment of a patient with gunshot injury to the head. During the treatment
      extremely infrequently occurring posttraumatic visual agnosia and posttraumatic
      epilepsy were observed. Twenty-two months after operation the patient is
      independent and professionally active.

PMID- 12046517
TI  - [Report on the Scientific Conference "On earlier diagnosis of intracranial
      tumors." Elblag, October 4, 2001].

PMID- 12046518
TI  - Relaxation modulus of denture base resin reinforced with woven glass fibers.
AB  - This study examined the reinforcing effect of woven glass fibers on the
      relaxation modulus by three-point loading of denture base resin. Three sandwich
      type flexure test specimens polymerized by heating were used, all 3 mm thick:
      glass fibers in compression (U type); glass fibers in the center (C type); and
      glass fibers in tension (L type). Unreinforced specimens (ACR) were produced as a
      control. The relaxation modulus after 8 sec from the start of stress (Er(8)) was
      calculated from stress relaxation curves. In the glassy state, the Er(8)s of the
      U and L types were greater than those of the ACR and C types. In the rubbery
      state (plateau region), the Er(8)s of the U and L types were greater than those
      of the ACR and C types. The woven glass fibers added to the U and L type
      specimens increased the relaxation modulus of PMMA near the oral temperature;
      moreover, they inhibited stress relaxation when the temperature increased.

PMID- 12046519
TI  - A study of cavity preparation by Er:YAG laser--observation of hard tooth
      structures by laser scanning microscope and examination of the time necessary to
      remove caries.
AB  - The purpose of this study was to observe and measure the morphological changes
      that occur in the hard tissue after the application of Er:YAG laser. Another
      objective was to evaluate and compare the duration of application of both the
      laser apparatus and a conventional cutting device. In this study, sound and newly
      extracted carious tissues were used. The morphological changes in hard tooth
      structures produced by Er:YAG laser irradiation were examined by using a laser
      scanning microscope. Results showed that appropriate laser irradiation was 100
      mJ/pulse for dentin, and 200 mJ/pulse for enamel. Also, the laser scanning
      microscope images were less damaged than the SEM images due to pretreatment of
      the specimens. The time taken to remove carious enamel by laser irradiation was
      slightly longer than the compared rotary cutting device; however, no differences
      between the two methods were observed in case of carious dentin removal.

PMID- 12046520
TI  - Anisotropy of tensile strengths of bovine dentin regarding dentinal tubule
      orientation and location.
AB  - The purpose of this study was to investigate the effects of the location and
      orientation of dentinal tubules in the tooth on tensile strengths of the dentin.
      Dumbbell-shaped specimens of 12 groups from various locations and dentinal tubule
      orientations were prepared. The tensile test was performed in distilled water at
      a temperature of 37 degrees C. The tensile strengths of the parallel to the
      orientation were significantly greater than those of the perpendicular to the
      orientation; the tensile strengths of the radicular dentin were significantly
      greater than those of the coronal dentin. Nevertheless, in the radicular dentin,
      the tensile strengths of the perpendicular to dentinal tubules differ with
      respect to tensile forces. These results suggest that tensile strength of the
      dentin varies according to the location and orientation of dentinal tubules in
      the tooth.

PMID- 12046521
TI  - Quantitative analysis of dental porcelain surfaces following different
      treatments: correlation between parameters obtained by a surface profiling
      instrument.
AB  - This investigation compared, by quantitative analysis, the surface roughness of
      dental porcelain submitted to three different treatments (glaze, trimming and
      polishing), utilizing a surface profiling instrument. The parameters Ra (median
      roughness), Rz (median of the maximum profile heights of five sample lengths),
      Rpm (median of the maximum profile heights related to the median line of five
      sample lengths), Pc (peak count per centimeter) and Rpm/Rz (proportional
      parameter) were evaluated. In addition, the correlation between Ra and the other
      parameters was analyzed. Based on the results obtained, it was seen that the Ra
      parameter did not present any correlation with the other parameters in some of
      the situations evaluated. This demonstrates that complementation of the
      measurement with other parameters is always necessary, providing a better
      evaluation of the functional properties of a surface.

PMID- 12046522
TI  - Effect of denture cleaner using ozone against methicillin-resistant
      Staphylococcus aureus and E. coli T1 phage.
AB  - We examined the bactericidal and virucidal effectiveness of a denture cleaner
      that uses ozone (ozone concentration, 10 ppm) against methicillin-resistant
      Staphylococcus aureus (MRSA) and T1 phage, respectively. In the bactericidal
      activity test, with the ozone supply turned on, the number of bacteria was 3.1 x
      10(3) CFU/mL at the beginning of the experiment, fell to 1.0 x 10(0) CFU/mL 10
      min later, and was 1.0 x 10(0) CFU/mL or less afterwards. In contrast, when the
      ozone supply was cut off (air bubble only), the number of bacteria was 3.4 x
      10(3) CFU/mL at the beginning of the experiment, and had fallen to 3.0 x 10(3)
      CFU/mL 60 min later (no statistically significant difference). In the virucidal
      activity test, the number of phages was 1.2 x 10(6) PFU/mL before ozone
      treatment, fell to about 1/10 of that number 10 min later, and was 6.1 x 10(0)
      PFU/mL 40 min later. These results indicate that the use of ozone in this denture
      cleaner is effective against MRSA and viruses.

PMID- 12046523
TI  - Porcelain veneer bonding to enamel with plasma-arc light resin curing.
AB  - The resin bond strength of plasma-arc curing in restorative dentistry was
      investigated in comparison to halogen-light curing with respect to two kinds of
      thickness, shade and opacity of porcelain laminate veneers. The bond strength of
      the light-cured resin was evaluated by shear tests and SEM observations of the
      fracture surfaces, and the results were interpreted in terms of the degree of
      resin polymerization. It was found that plasma-arc curing for 6 s was sufficient
      to obtain bond strengths similar to those of specimens polymerized with halogen
      light for 40 s, whereas the plasma-arc curing time needed to be doubled to 12 s
      in order to achieve similar failure patterns for a darker-shade porcelain of 2 mm
      thickness. The bond strength achieved by plasma-arc curing was found to be
      relatively unaffected by the shade or opacity of porcelain.

PMID- 12046524
TI  - A comparative study of fluoride-releasing adhesive resin materials.
AB  - One of the most important and exciting properties of recently introduced dental
      restorative materials is their ability to release fluoride ions, as this has
      several advantageous effects on tooth structures. They have been extensively used
      as fluoride-releasing filling and luting materials. Recently, fluoride-releasing
      adhesive resins and fluoride-releasing adhesive resin cement have been developed
      and introduced for clinical use. The purpose of this study was to evaluate the
      fluoride release from these adhesive resins and the fluoride uptake by both
      enamel and dentin, as well as the acid-resistance of these tooth structures.
      Based on our results, we conclude that fluoride-releasing adhesive resins and
      luting cements are useful for the prevention of initial or secondary caries,
      especially along the margins of restorations.

PMID- 12046525
TI  - [Surgical treatment of foot diseases and injuries].

PMID- 12046526
TI  - [Distant pulse-wave lithotripsy in the Central Clinical Air Force Hospital ].
AB  - With participation of the specialists from the 7th Central Military Clinical
      Aviation Hospital 4 pulse-wave complexes "Urat-P", "Urat-P2", "Ulitho",
      "Cholelithotriptor" were developed and introduced into clinical practice of the
      hospital. Distant pulse-wave lithotripsy was conducted 3035 patients (358 persons
      from flying staff). It is the main method of urolithiasis treatment, especially
      in the flying staff. Its efficiency is more than 96%. The modern models of
      lithotriptors are effective in destruction of biliary and urinary calculi and the
      applied parameters of wave impulses don't impact on the organs and tissues. The
      sphere of use of pulse-wave effect in the clinical practice was extended.

PMID- 12046527
TI  - [Distant shock wave lithotripsy in the complex treatment of cholelithiasis].

PMID- 12046528
TI  - [Clinical expert evaluation of the cardiovascular system in pilots with
      idiopathic prolapse of the mitral valve].

PMID- 12046529
TI  - [Early diagnosis, treatment, and expert examination of sarcoidosis in the flying
      personnel].

PMID- 12046530
TI  - [Clinical course of duodenal ulcer in clean-up workers of the Chernobyl nuclear
      power plant accident: long-term follow-up study].

PMID- 12046531
TI  - [Regeneration of the gastric epitheliocytes during treatment of duodenal ulcer
      with pariet].

PMID- 12046532
TI  - [Medical support of peace keeping forces in the Georgian-Abkhazian armed conflict
      zone].
AB  - Since 1994 in the settlement of Georgian-and-Abkhazian armed conflict together
      with wide spectrum of means of political, diplomatic and economical character the
      Russian peace-making forces effectively use the operation for peace support.
      Taking into account the number of peace-making forces, the problems the solve and
      conditions of activity the staff of military medical service was presented by the
      head of medical service of united headquarters for peace support; by the medical
      platoons of battalions strengthened by physician, sanitary and medical equipment,
      additional medical things; by the medical station with infirmary (15 permanent
      beds); by the reanimation mobile group; by the emergency medical service group.
      The quality of medical support and successful solution of peace-making problems
      depend first of all on the management effectiveness, quality of medical
      specialist selection, discipline and professional training. It allows to work out
      the proposals for improvement of peace-making contingent's medical support in the
      zone of Georgian-and-Abkhazian armed conflict.

PMID- 12046533
TI  - [HIV infection in the country and armed forces of Russian Federation: problems
      and ways of their resolution].

PMID- 12046535
TI  - [Recovery physiotherapy of myopathy in flying personnel of the Air Forces].

PMID- 12046534
TI  - [Current problems in prophylaxis and treatment of acute decompression disease of
      mild degree].
AB  - The authors discuss the causes leading to the rise of acute decompression illness
      in the amateur skin-divers. They include the insufficient training of most skin
      drivers in the basis of diving physiology and medicine, the underwater dipping
      without consideration of individual sensitivity to decompression illness and
      nitrogen narcotic action, disorders in decompression regimens, non-observance of
      behavior rules after dipping, use of air transport immediately after dipping. The
      case of delayed treatment of decompression illness is described. The data
      concerning the possibility of chronic decompression illness formation due to the
      action of asymptomatic decompression gasformation and acute decompression illness
      of mild degree are presented. The authors propose the system of measures that
      would help to decrease the incidence of disease and to make the treatment of
      decompression illness more effective.

PMID- 12046536
TI  - [Methodological problems of diagnosis of color vision in flying personnel].

PMID- 12046537
TI  - [Law basis of psychohygiene and psychoprophylaxis in the military personnel].

PMID- 12046538
TI  - [Development of mobile medical facilities in the military health service].

PMID- 12046539
TI  - [Novel wound dressings in the treatment of burns and wounds].

PMID- 12046540
TI  - [The Central Clinical Air Force Hospital of the Ministry of Defence of Russian
      Federation: history landmarks].

PMID- 12046541
TI  - [History of the activity of the Central Military Hospital Committee].

PMID- 12046542
TI  - [Various medical problems in preparation of medical schools to teaching a new
      specialty "Extreme medicine physician"].

PMID- 12046543
TI  - Sequence analysis and genotypes of glutamate rich protein of Plasmodium
      falciparum isolates from different malaria endemic areas in China.
AB  - OBJECTIVE: To sequence the gene encoding glutamate rich protein (GLURP) and
      identify the genotypes of geographically different Plasmodium falciparum (P. f)
      isolates from China. METHODS: The gene of R2 repeat region of GLURP was amplified
      by nested polymerase chain reaction and cloned into T-vector. The nucleotide
      sequence of GLURP gene was determined by automatic sequencer (Dideoxy termination
      method) and analyzed by DNA Star software. RESULTS: At least 7 different GLURP
      genotypes ranging from 600 bp to 1,500 bp were found in Yunnan and Hainan
      provinces. R2 region of GLURP gene consisted of several repeat units. Each repeat
      unit was composed of 19-20 residues which were shown to be highly conserved.
      GLURP gene was also size polymorphic due to differences in the number of repeat
      units, whereas the repeat sequence was conserved. Sequence analysis showed that
      DNA sequences and deduced amino acid sequences were highly homologous among the
      geographically dispersed isolates or various isolates from the same geographical
      region. No obvious differences were found in the GLURP gene sequences among
      geographically different isolates. CONCLUSION: GLURP gene is highly structure
      conserved and size polymorphic, and so is useful in searching for malaria vaccine
      candidate antigen and developing a genotyping method for malaria research.

PMID- 12046544
TI  - Studies on hypokalemia induced by trimethyltin chloride.
AB  - OBJECTIVES: To determine the possible relationship between plasma potassium
      concentration and severity of acute trimethyltin chloride (TMT) poisoning and to
      assess the mechanism of TMT induced hypokalemia. METHODS: SD rats were treated
      with various dosages of TMT (i.p.). All the indices were measured and analysed
      for determining their possible relations with plasma K+. RESULTS: With increase
      of dosage, the plasma K+ level dropped rapidly, and deaths appeared more quickly.
      The LD50 of TMT (i.p.) was 14.7 mg/kgbw. In the low dosage group (10 mg/kgbw),
      the plasma K+ level dropped slowly with the lowest dosage on day 6 (4.85 mmol/L).
      It rose again on day 11 (5.06 mmol/L), and recovered on day 28. The poisoning
      signs corresponded with decline of the span of K+ level. The plasma Na+ level
      dropped half an hour after TMT treatment, but recovered 24 h later. In the high
      dosage group (46.4 mg/kgbw), the levels of plasma K+ and Na+ fell rapidly within
      half an hour (P < 0.05), the intracellular potassium concentration of RBC did not
      decrease obviously (P > 0.05), the activities of Na(+)-K(+)-ATPase and Mg(2+)
      ATPase in RBC membrane were depressed remarkably (P < 0.01, P < 0.05,
      respectively), the plasma aldosterone concentrations rose as high as tenfold (P <
      0.01), the arterial blood pH fell from 7.434 to 7.258 (P < 0.01), pCO2 was raised
      from 29.62 to 45.33 mmHg (P < 0.01). In the 24 h urine test, when rats were
      treated with TMT (21.5 mg/kgbw, i.p.), urine volume, urinary potassium, sodium
      and chloride increased significantly in comparison with those in the controls (P
      < 0.01). CONCLUSION: TMT could induce hypokalemia in SD rats. The available
      evidence suggests that TMT can induce acute renal leakage of potassium. At the
      same time, a significant rise of plasma aldosterone may play an important role in
      promoting potassium leakage from kidney to result in severe hypokalemia with
      inhaling acid-base abnormalities produced, which aggravate the poisoning
      symptoms. In the end the rats would die of respiratory failure.

PMID- 12046545
TI  - Evaluation of CC2 as a decontaminant in various hydrophilic and lipophilic
      formulations against sulphur mustard.
AB  - OBJECTIVE: To evaluate CC2 (N, N'-dichloro-bis [2, 4, 6-trichlorophenyl] urea) in
      various hydrophilic and lipophilic formulations as a personnel decontaminant for
      sulphur mustard (SM). METHODS: Twenty percent of CC2 was prepared as a suspension
      or ointment with various chemical agents and its stability was evaluated by
      active chlorine assay. The efficacy was evaluated in mice by recording the
      mortality after applying 29 LD50 of SM (LD50 = 8.1 mg/kg dermally) and
      decontaminating it after 2 min with 200 mg of the formulation. Studies were also
      carried out with 10% and 20% CC2 in acacia and hydroxypropyl cellulose, and the
      suspensions were stored in polyethylene containers. The stability of the
      suspensions was evaluated by active chlorine assay. The efficacy was evaluated by
      recording the mortality after applying 29 LD50 of SM in mice and 12 LD50 of SM in
      rats (LD50 = 2.4 mg/kg dermally), and decontaminating it with the formulations.
      LD50 by different routes and primary skin irritation test of CC2 were also
      carried out. RESULTS: CC2 reacted with peanut oil and neem oil, and was unstable
      in povidone iodine and Fuller's earth. Good stability was achieved with petroleum
      jelly, honey, polyvinyl pyrrolidone, calamine lotion, acacia and hydroxypropyl
      cellulose. Though CC2 was stable in lipophilic formulations, it did not protect
      the animals. The hydrophilic formulations particularly acacia and hydroxypropyl
      cellulose gave very good protection and was stable in the polyethylene containers
      for a period of 1 year. The efficacy of 20% CC2 was better than 10% CC2. The oral
      and dermal LD50 of CC2 was found to be above 5.0 g/kg. CC2 was also found to be
      nonirritant. CONCLUSION: Twenty percent of CC2 in hydroxypropyl cellulose is
      better with respect to stability, efficacy and ease of decontamination. CC2 is
      also a safe chemical.

PMID- 12046546
TI  - Yeast one-hybrid system used to identify the binding proteins for rat glutathione
      S-transferase P enhancer I.
AB  - OBJECTIVE: To detect the trans-factors specifically binding to the strong
      enhancer element (GPEI) in the upstream of rat glutathione S-transferase P (GST
      P) gene. METHODS: Yeast one-hybrid system was used to screen rat lung MATCHMAKER
      cDNA library to identify potential trans-factors that can interact with core
      sequence of GPEI(cGPEI). Electrophoresis mobility shift assay (EMSA) was used to
      analyze the binding of transfactors to cGPEI. RESULTS: cDNA fragments coding for
      the C-terminal part of the transcription factor c-Jun and rat adenine nucleotide
      translocator (ANT) were isolated. The binding of c-Jun and ANT to GPEI core
      sequence were confirmed. CONCLUSIONS: Rat c-jun transcriptional factor and ANT
      may interact with cGPEI. They could play an important role in the induced
      expression of GST-P gene.

PMID- 12046547
TI  - Antitumorigenic potential of diallyl sulfide in Ehrlich ascites tumor bearing
      mice.
AB  - OBJECTIVE: To study the effects of diallyl sulfide (DAS), an organosulfur
      compound present in garlic (Allium sativum), on the life span of ehrlich ascites
      (EA) tumor bearing Swiss albino mice, cytotoxicity and angiogenesis. METHODS: EA
      tumor cells were maintained by serial transplantation in peritoneal cavity of
      male Swiss albino mice. EA tumor cells were inoculated at concentrations of 1 x
      10(6) EA cells, 2.5 x 10(6) EA cells and 5 x 10(6) EA cells. DAS was given in 0.2
      ml normal saline i.p., daily for seven days followed one hour later by
      inoculation with EA cells in respective groups. RESULTS: The results revealed
      that administration of DAS increased the life span of EA tumor bearing animals by
      more than 25 percent. A significant dose dependant cytotoxic response of DAS was
      also observed on EA tumor cells. DAS was also found to inhibit the angiogenesis
      in EA tumor bearing mice in a dose dependent manner. CONCLUSION: It is suggested
      that DAS may exert its anticarcinogenic effects by more than one mechanism and is
      a useful chemopreventive and chemotherapeutic agent.

PMID- 12046548
TI  - Oxidative stress in patients with acute coxsackie virus myocarditis.
AB  - OBJECTIVE: To study the state of oxidative stress in patients with acute
      coxsackie virus myocarditis (ACM), and to investigate the pathological chain
      reactions of a series of free radicals and oxidative and lipoperoxidative damages
      in their bodies. METHODS: Eighty ACM patients and 80 healthy adult volunteers
      (HAV) were enrolled in a case-control study, in which concentrations of nitric
      oxide (NO) in plasma, lipoperoxides (LPO) in plasma and LPO in erythrocytes
      (RBC), vitamin C (VC), vitamin E (VE) and beta-carotene (beta-CAR) in plasma as
      well as activities of superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GSH-Px) in RBC were determined by using spectrophotometric assays.
      RESULTS: Compared with the average values (AV) of the above biochemical
      parameters (BP) in the HAV group, the AV of NO in plasma, and LPO in plasma and
      RBC in the ACM group were significantly increased (P = 0.0001), while the AV of
      VC, VE, beta-CAR, SOD, CAT and GSH-Px in the ACM group were significantly
      decreased (P = 0.0001). The values of the above BP were used to estimate the
      relative risk ratio (RR) between the ACM group and the HAV group; the RR and its
      95% confidence interval were 12.467 (5.745-27.051), 4.333 (2.126-8.834), 6.517
      (3.225-13.618), 3.310 (1.598-6.858), 31.000 (12.611-76.201), 4.663 (2.228-9.759),
      11.769 (5.440-25.462), 3.043 (1.486-6.229) and 6.594 (3.045-14.281) respectively,
      and their P levels ranged from 0.002 to 0.0001. The results were as follows: D =
      22.143 - 0.017SOD + 0.008NO + 0.244LPO in RBC, Eigenvalue = 13.659, Canonical
      correlation = 0.965, Wilks' lambda = 0.068, chi 2 = 420.212, P = 0.0001. The
      correct rate of discrimination to the ACM group and to the HAV group was 87.5%
      and 95.0%, respectively, and 91.3% of originally grouped cases was correctly
      classified. CONCLUSION: The findings in this study suggested that the oxidative
      stress in bodies of ACM patients was severely aggravated, and marked high
      oxidative constituents and low antioxidants and antioxidases in the human body
      might increase the relative risk of inducing acute coxsackie virus myocarditis,
      and measuring the values of NO in plasma, SOD and LPO in RBC might increase the
      correct rates of discriminatory analysis of the ACM.

PMID- 12046549
TI  - Improvement of chemically-activated luciferase gene expression bioassay for
      detection of dioxin-like chemicals.
AB  - OBJECTIVE: To improve the chemically-activated luciferase expression (CALUX)
      bioassay for detection of dioxin-like chemicals (DLCs) based on the toxicity
      mechanisms of DLCs. METHODS: A recombinant vector was constructed and used to
      transfect human hepatoma (HepG2). The expression of this vector was 10-100 folds
      higher than that of pGL2 used in previous experiments. The transfected cells
      showed aromatic hydrocarbon receptor (AhR)-meditated luciferase gene expression.
      The reliability of luciferase induction in this cell line as a reporter of AhR
      mediated toxicity was evaluated, the optimal detection time was examined and a
      comparison was made by using the commonly used ethoxyresoufin-O-deethylase (EROD)
      activity induction assay. RESULTS: The results suggested that the luciferase
      activity in recombinant cells was peaked at about 4 h and then decreased to a
      stable activity by 14 h after TCDD treatment. The detection limit of this cell
      line was 0.11 pmol/L, or 10-fold lower than in previous studies, with a linear
      range from 1 to 100 pmol/L, related coefficient of 0.997, and the coefficient of
      variability (CV) of 15-30%. CONCLUSION: The luciferase induction is 30-fold more
      sensitive than EROD induction, the detection time is 68 h shorter and the
      detection procedure is also simpler.

PMID- 12046550
TI  - Restorative effects of zinc and selenium on cadmium-induced kidney oxidative
      damage in rats.
AB  - OBJECTIVE: To investigate whether cadmium-induced oxidative stress in the kidney
      is influenced by zinc and selenium. METHODS: Five groups of rats were maintained:
      (A) Cd (CdCl2, 400 micrograms.kg-1.day-1 intraperitoneal injection); (B) Cd + Zn
      (ZnCl2, 20 mg.kg-1.day-1 hypodermic injection); (C) Cd + Se (Na2SeO3, 350
      micrograms.kg-1.day-1 via a stomach tube); (D) Cd + Zn + Se; (E) treated with
      physiological saline as a sham-handled control. The rats were given treatment for
      a period of 4 weeks. The activities of superoxide dismutase (SOD), glutathione
      peroxidase (GH-Px), catalase (CAT), and the level of malondialdehyde (MDA) in the
      kidney tissue were measured to assess the oxidative stress. Urinary lactate
      dehydrogenase (LDH) activity was used as an indicator of tubular cell damage
      caused by lipid peroxidation. RESULTS: In group C and D, activities of SOD (110.5
      +/- 5.2, 126.8 +/- 7.0; P < 0.05) and GSH-Px (85.7 +/- 4.9, 94.6 +/- 7.3; P <
      0.05) were higher than those in group A (84.7 +/- 3.3; 56.9 +/- 3.8); and in
      group B, only the activity of GSH-Px (80.0 +/- 4.3, P < 0.01) increased in
      comparison with that in group A (56.9 +/- 3.8). Significant increase of MDA (P <
      0.05) was seen in group B (31.1 +/- 4.7) and C (35.0 +/- 4.1) when compared with
      control values (17.2 +/- 1.8). No difference was found in the level of MDA
      between group D (18.9 +/- 2.6) and control. The activity of LDH in urine of
      control group (0.06 +/- 0.02) was lower than that of group A (0.46 +/- 0.19, P <
      0.05), B (0.10 +/- 0.05, P < 0.05) and C (0.14 +/- 0.07, P < 0.05), and there was
      no significant change between control (0.06 +/- 0.02) and group D (0.08 +/-
      0.02). CONCLUSION: Zinc or selenium could partially alleviate the oxidative
      stress induced by cadmium in kidney, but administration cadmium in combination
      with zinc and selenium efficiently protects kidney from cadmium-induced oxidative
      damage.

PMID- 12046551
TI  - Single nucleotide polymorphisms in CAPN10 gene of Chinese people and its
      correlation with type 2 diabetes mellitus in Han people of northern China.
AB  - OBJECTIVE: To investigate the distribution of single nucleotide polymorphisms
      (SNPs) in CAPN10 gene in Chinese population and their relation with type 2
      diabetes mellitus in Han people of Northern China. METHODS: CAPN10 gene was
      sequenced to detect SNPs in different nationalities of China. Five SNPs were
      chosen to perform case-control study and haplotype analysis in 156 normal Han
      people of Northern China and 173 type 2 diabetes. One SNP was also analyzed with
      transmission-disequilibrium test (TDT) and sib transmission-disequilibrium test
      (STDT) in 68 type 2 diabetes pedigrees (377 people). RESULTS: A total of 40 SNPs
      were identified in length of 8,936 bp, with an average of 1 in every 223 bp. The
      SNPs in CAPN10 gene did not distribute evenly and the SNPs in Chinese were
      different from those reported in Mexican American. There was no significantly
      statistical difference in the allele frequency of the 5 SNPs between case and
      control, and the haplotype frequencies in the two groups were not significantly
      different. No positive results was found in TDT and STDT analysis. CONCLUSIONS:
      The SNP distribution of CAPN10 gene differs in different nationalities. The
      studied SNPs in CAPN10 gene may not be the major susceptibility ones of type 2
      diabetes mellitus in Han people of Northern China.

PMID- 12046552
TI  - Methodology for the assessment of burden of smear-positive pulmonary TB and its
      infectivity.
AB  - OBJECTIVE: The study investigated the burden of smear-positive pulmonary TB and
      its infectivity using DALY (disability-adjusted life year) as an indicator.
      METHODS: An assumed cohort of 2,000 cases was set up based on the age-specific
      incidence of 794 newly registered smear-positive cases in Beijing in 1994.
      Prognostic trees and model diagrams of infectivity under natural history and
      DOTS(directly observed treatment, short-course) strategy were established
      according to the epidemiological evidence. RESULTS: The results showed that 29.6%
      of DALYs would be neglected if the burden caused by the infectivity was not
      considered. CONCLUSION: DOTS strategy may reduce 97.3% of the number of potential
      cases infected, 92.9% of DALYs related to TB-patients themselves, and 99.9% of
      DALYs caused by TB's infectivity as well.

PMID- 12046553
TI  - Predictive values of body mass index and waist circumference for risk factors of
      certain related diseases in Chinese adults--study on optimal cut-off points of
      body mass index and waist circumference in Chinese adults.
AB  - OBJECTIVE: For prevention of obesity in Chinese population, it is necessary to
      define the optimal range of healthy weight and the appropriate cut-off points of
      BMI and waist circumference for Chinese adults. The Working Group on Obesity in
      China under the support of International Life Sciences Institute Focal point in
      China organized a meta-analysis on the relation between BMI, waist circumference
      and risk factors of related chronic diseases (e.g., high diabetes, diabetes
      mellitus, and lipoprotein disorders). METHODS: 13 population studies in all met
      the criteria for enrollment, with data of 239,972 adults (20-70 year) surveyed in
      the 1990s. Data on waist circumference was available for 111,411 persons and data
      on serum lipids and glucose were available for more than 80,000. The study
      populations located in 21 provinces, municipalities and autonomous regions in
      mainland China as well as in Taiwan. Each enrolled study provided data according
      to a common protocol and uniform format. The Center for data management in
      Department of Epidemiology, Fu Wai Hospital was responsible for statistical
      analysis. RESULTS AND CONCLUSION: The prevalence of hypertension, diabetes,
      dyslipidemia and clustering of risk factors all increased with increasing levels
      of BMI or waist circumference. BMI at 24 with best sensitivity and specificity
      for identification of the risk factors, was recommended as the cut-off point for
      overweight, BMI at 28 which may identify the risk factors with specificity around
      90% was recommended as the cut-off point for obesity. Waist circumference beyond
      85 cm for men and beyond 80 cm for women were recommended as the cut-off points
      for central obesity. Analysis of population attributable risk percent illustrated
      that reducing BMI to normal range (< 24) could prevent 45%-50% clustering of risk
      factors. Treatment of obese persons (BMI > or = 28) with drugs could prevent 15%
      17% clustering of risk factors. The waist circumference controlled under 85 cm
      for men and under 80 cm for women, could prevent 47%-58% clustering of risk
      factors. According to these, a classification of overweight and obesity for
      Chinese adults is recommended.

PMID- 12046555
TI  - Profiles in professionalism: 2001 ACD awards.

PMID- 12046556
TI  - Proceedings of the 3rd International Symposium on Diabetes Mellitus and its
      Complications. Budapest, Hungary. July 2-6, 2001.

PMID- 12046554
TI  - In Memoriam. Univ.-Prof. Dr. Med. Dr. H. C. Horst Bickel, PhD, FRCP. 28 June 1918
      -1 December 2000.

PMID- 12046557
TI  - Changing the delivery of diabetes care.

PMID- 12046558
TI  - [The school health program in the municipality of Ribeirao Preto].
AB  - The present article reports on the trajectory of the Primary School Health Care
      Program (PROASE) at the municipality of Ribeirao Preto and describes some
      reflections about this proposal.

PMID- 12046559
TI  - [Faculty's behavior in undergraduate nursing teaching: the students' perception].
AB  - The purposes of the present study are: to identify faculty's predominant
      behaviors in undergraduate nursing teaching, according to the students'
      perception and to classify them in different groups of faculty, relating them to
      the teaching framework. Data were obtained through questionnaires, applied to
      fifty-two students from the Federal University of Mato Grosso do Sul. Considering
      the results obtained from both periods, we can conclude that there is a certain
      plurality in the faculty behaviors, with a predominance of teachers concerned
      about contents, methods and techniques, with characteristics of the traditional,
      behaviorist and cognitive frameworks.

PMID- 12046560
TI  - [Nursing diagnoses in a high risk pregnant woman based on Orem's self-care
      theory: a case study].
AB  - This work concerns a descriptive research with a qualitative approach which aimed
      to identify nursing diagnoses in high-risk pregnant women based on Orem's self
      care theory. The following nursing diagnoses were identified: deficit of liquid
      volume, anxiety, altered family process, handicapped communication, handicapped
      physical mobility, among others. The results showed the importance of the nursing
      process execution supported on an assistance pattern, for the identification of
      nursing diagnoses as well as the feasibility of the patient's engagement in self
      care.

PMID- 12046561
TI  - [Therapeutic use of nitric oxide: implications for nursing].
AB  - Nitric oxide (NO) is a gas that transmits signals in the organism. Such signal
      transmission takes place by means of the gas synthesis and release in different
      cell types. After it is released, the gas penetrates the membrane of a
      neighboring cell and regulates its function. Such mechanism represents an
      entirely new signaling principle in biological systems. The discoverers of NO as
      a signaling molecule were awarded the Nobel Prize in Medicine and Physiology in
      1998. This discovery has revolutionized medicine and originated new treatments
      for old problems. In this study, we review the role of NO in some pathologies
      such as sepsis, arterial hypertension and pulmonary hypertension and Nitric Oxide
      is explained in terms of its current merit for treatment and its impact on
      nursing care.

PMID- 12046562
TI  - [In search of a definition of current guidelines for outlining studies on
      children's and school-age adolescents' health].
AB  - This work is a reflection of the search for a definition of current guidelines
      for outlining studies on the assistance to the child's and school-age
      adolescent's health based on current literature and on the discussion among
      professionals in the fields of Health and Education. The guidelines: Assistance
      to the child's and school-age adolescent's health; Education, Health and Society-
      current historical transformation; Health, Education and Life Conditions lead to
      the following questions: how to promote the child's and school-age adolescent's
      health within the principles of the Unified Health System (SUS) and how to deal
      with issues such as Health and Education in an inter-sectorial, multi
      professional and interdisciplinary fashion by taking into account the New
      National Curricular Standards? In the conclusion, actions are proposed to
      eradicate the idea that students are at fault in relation to school failure as
      well as to change the vision based on current concepts and standings by
      considering all the changes that have taken place in the field of education with
      the new Law of Bases and Directives and the recent introduction and application
      of the New National Curricular Standards.

PMID- 12046563
TI  - [The work situation of nursing personnel in the context of an Argentinian
      hospital: a study from the ergonomics perspective].
AB  - The present study aimed at characterizing the work situation of the nursing
      personnel from an Argentine Hospital through the identification of the
      characteristics of the workers, the executed activities and the work environment,
      using the methodological fundamentals of ergonomics. In order to diagnose the
      work situation, the author performed 74 interviews with the workers, 17 nurses
      and 57 nursing auxiliaries. Findings showed that the work situation in the
      studied presents problems related to the work organization, tasks division, lack
      of a policy directed to improve professional capacities and safety at work,
      promotion of worker's health and adequacy of the materials, equipment. The
      authors presented suggestions based on ergonomics in order to minimize or to
      eliminate the detected problems.

PMID- 12046564
TI  - [Importance of oral health for adolescents from different social levels in the
      municipality of Ribeirao Preto].
AB  - The objective of the present study is to know the importance of buccal health for
      adolescents of different social strata, identifying the importance of dental
      aesthetics, and the care that these students take in relation to their buccal
      health. The methodological process adopted in this investigation is of
      qualitative nature, using as technique of collection of data the semistructured
      interview. We know the importance of buccal health in several contexts of their
      lives, as in their personal appearance, sexuality, employment, and general
      health. This investigation allows us to know the motivations of adolescents to
      preserve their buccal health, and we believe to be so valid to develop health
      promotion through health education.

PMID- 12046565
TI  - [Informed consent for laryngectomy: a university hospital study].

PMID- 12046566
TI  - [Nursing diagnoses in women attending a family planning service].
AB  - The purpose of this study was to identify nursing diagnoses in women enrolled in
      a family planning program. An instrument of data collection was elaborated
      according to the Functional Health Patterns. The sample consisted of 100 adult
      women. Forty-nine nursing diagnoses, of which 9 with a frequency equal or higher
      to 45.0% were identified. Further studies are still needed in institutions that
      offer assistance in the area of family planning in order to examine if the
      nursing diagnoses found in these women can be generalized to the population.

PMID- 12046567
TI  - [Protocol for the preparation of preschool children to venous puncture using
      therapeutic play].
AB  - This exploratory-descriptive study aims at elaborating a protocol, using
      therapeutic play, for the preparation of preschool children to venous puncture
      and also at testing its efficiency and applicability. The children that attended
      the play session were more cooperative when they were punctured. They understood
      the need and technical aspects of this clinical procedure; manifested their
      feelings, elaborated familiar and hospital situations that resulted in a better
      relationship with the other children and the nursing team. Authors concluded that
      this protocol is feasible and useful and suggested that it should be incorporated
      in the nursing care plan to hospitalized children.

PMID- 12046568
TI  - [Hospitalized hypertensive adults: perception about disease severity and quality
      of life].
AB  - The purpose of this descriptive study was to identify the perception of life
      quality in hospitalized hypertensive adults, confronting the data related to life
      quality with perceptions of disease gravity. The population comprised 83 patients
      hospitalized in the Medical Clinic of the University Hospital at the Federal
      University of Mato Grosso do Sul (UFMS). The data were collected by means of
      interviews using a health evaluation instrument that had been translated and
      validated in Brazil, the SF-36. The main results showed that, in view of the
      studied patients, the perception of life quality as well as the perception of
      absence of disease gravity were good.

PMID- 12046569
TI  - [Analysis of maternal mortality in the municipality of Ribeirao Preto -- SP-- in
      1991-1995].
AB  - This study aims at learning about and identifying the causes leading to maternal
      death. Data were obtained from the Ribeirao Preto Committee for Studies and
      Prevention of Maternal Death and from obituaries. It is an exploratory study in
      which 72 maternal deaths occurring in Ribeirao Preto were analyzed from 1991 to
      1995. In 1995, the maternal death rate was 60.3 in 100,000 births, with the
      predominance of avoidable causes, such as hemorrhage (33.3%), other causes
      (26.4%), hypertension (15.3%), abortion (11.1%), infection (8.3%) and puerperium
      (5.6%). Maternal death is a public health problem which must be faced by
      government authorities.

PMID- 12046570
TI  - Eighth Japanese-German Workshop on Molecular and Cellular Aspects of
      Carcinogenesis.

PMID- 12046571
TI  - [Proceedings of the XXV National Congress of the Spanish Association for the
      Study of the Liver. Madrid, Spain, 24-26 February 2000].

PMID- 12046572
TI  - The pediatric use of bilevel positive airway pressure therapy for obstructive
      sleep apnea syndrome: a retrospective review with analysis of respiratory
      parameters.
AB  - The purpose of this study was objective documentation of clinical benefits of
      bilevel positive airway pressure in pediatric patients with obstructive sleep
      apnea. We performed a retrospective chart review and data collection/analysis in
      a suburban tertiary care children's hospital. The study consisted of 10 pediatric
      patients (age range: 3 to 18 years); 3 patients had craniofacial abnormalities, 1
      patient had neuromuscular disease, and 6 patients were obese. Eleven-channel
      polysomnography and support with bilevel positive airway pressure were used. We
      measured obstructive sleep apnea indices, lowest oxygen saturation rate, and
      average breath lengths before and after bilevel positive airway pressure use. We
      found that the apnea index decreased from 19.7 +/- 26.46 to 0.82 +/- 1.01, the
      lowest oxygen saturation increased from 75.60% +/- 14.93% to 89.50% +/- 5.50%,
      and breath length increased from 3.22 +/- 0.95 to 3.68 +/- 0.82. Bilevel positive
      airway pressure may be considered as a treatment modality for pediatric patients
      with obstructive sleep apnea.

PMID- 12046573
TI  - Optimization of activated sludge designs using genetic algorithms.
AB  - We describe a framework in which a genetic algorithm (GA) and a static activated
      sludge (AS) treatment plant design model (WRC AS model) are used to identify low
      cost activated sludge designs that meet specified effluent limits (e.g. for BOD,
      N, and P). Once the user has chosen a particular process (Bardenpho, Biodenipho,
      UCT or SBR), this approach allows the parameterizations for each AS unit process
      to be optimized systematically and simultaneously. The approach is demonstrated
      for a wastewater treatment plant design problem and the GA-based performance is
      compared to that of a classical nonlinear optimization approach. The use of GAs
      for multiobjective problems such as AS design is demonstrated and their
      application for reliability-based design and alternative generation is discussed.

PMID- 12046574
TI  - Institut Philippe Pinel de Montreal v. Dion.

PMID- 12046575
TI  - Mental health and developmental disabilities confidentiality act.

PMID- 12046577
TI  - Determination of death.

PMID- 12046576
TI  - In re Alleged Mental Illness of Kinzer.

PMID- 12046578
TI  - Abstracts from the 10th Annual Scientific Meeting of the Wilderness Medical
      Society. Squaw Valley, California, USA. August 7-13, 1994.

PMID- 12046579
TI  - Buildings. Castles in the air.

PMID- 12046580
TI  - Buildings. The next generation.

PMID- 12046581
TI  - Buildings. A touch of spice.

PMID- 12046582
TI  - Nanoscience: underlying physical concepts and phenomena. Proceedings of the
      Arthur M. Sackler Colloquium of the National Academy of Sciences. May 18-20,
      2001. Washington, DC, USA.

PMID- 12046583
TI  - Practice Brief. Starting a consulting business.

PMID- 12046584
TI  - Profile. Making a commitment to privacy protection.

PMID- 12046586
TI  - Genetic versus environmental etiology of the metabolic syndrome among male and
      female twins.

PMID- 12046585
TI  - HMOs--HMO Act--coverage of basic health serices--home health care.  Juliano v.
      HMO of New Jersey.

PMID- 12046587
TI  - Idopathic acute pancreatitis: Is EUS worth doing?

PMID- 12046588
TI  - Recommendations for greater accuracy in the standard care for the detection of
      early Barrett's esophageal cancer.

PMID- 12046589
TI  - What should be the standard care for cancer surveillance, diagnosis of dysplasia,
      and the decision for colectomy in chronic inflammatory bowel disease?

PMID- 12046590
TI  - cAMP and ras signalling independently control spore germination in the
      filamentous fungus Aspergillus nidulans.
AB  - The role of cAMP signalling during germination of asexual spores (conidia) of the
      filamentous fungus Aspergillus nidulans was investigated. A. nidulans strains
      defective for adenylate cyclase (CyaA) or for the functionally overlapping cAMP
      dependent protein kinase (PkaA) and newly characterized SchA protein kinase,
      homologous to Saccharomyces cerevisiae Sch9, show altered trehalose mobilization
      and kinetics of germ tube outgrowth, in addition to other defects in colony
      formation. cAMP-dependent trehalose breakdown is triggered by the addition of a
      carbon source independently of further catabolism, suggesting that cAMP
      signalling controls early events of conidial germination in response to carbon
      source sensing. Additional results suggest that cAMP has targets other than PkaA
      and SchA and that PkaA retains activity in the absence of cAMP. Conversely, PkaA
      regulates cAMP levels in A. nidulans because these are elevated by approximately
      250-fold in a strain that lacks PkaA. Furthermore, analysis of mutant strains
      impaired in both adenylate cyclase and RasA GTPase previously implicated in the
      control of A. nidulans spore germination suggested that RasA and cAMP signalling
      proceed independently during germination in A. nidulans.

PMID- 12046591
TI  - Co-ordinate regulation of distinct host cell signalling pathways by
      multifunctional enteropathogenic Escherichia coli effector molecules.
AB  - Enteropathogenic Escherichia coli (EPEC) is a major cause of paediatric diarrhoea
      and a model for the family of attaching and effacing (A/E) pathogens. A/E
      pathogens encode a type III secretion system to transfer effector proteins into
      host cells. The EPEC Tir effector protein acts as a receptor for the bacterial
      surface protein intimin and is involved in the formation of Cdc42-independent,
      actin-rich pedestal structures beneath the adhered bacteria. In this paper, we
      demonstrate that EPEC binding to HeLa cells also induces Tir-independent,
      cytoskeletal rearrangement evidenced by the early, transient formation of
      filopodia-like structures at sites of infection. Filopodia formation is dependent
      on expression of the EPEC Map effector molecule - a protein that targets
      mitochondria and induces their dysfunction. We show that Map-induced filopodia
      formation is independent of mitochondrial targeting and is abolished by cellular
      expression of the Cdc42 inhibitory WASP-CRIB domain, demonstrating that Map has
      at least two distinct functions in host cells. The transient nature of the
      filopodia is related to an ability of EPEC to downregulate Map-induced cell
      signalling that, like pedestal formation, was dependent on both Tir and intimin
      proteins. The ability of Tir to downregulate filopodia was impaired by disrupting
      a putative GTPase-activating protein (GAP) motif, suggesting that Tir may possess
      such a function, with its interaction with intimin triggering this activity.
      Furthermore, we also found that Map-induced cell signalling inhibits pedestal
      formation, revealing that the cellular effects of Tir and Map must be co
      ordinately regulated during infection. Possible implications of the
      multifunctional nature of EPEC effector molecules in pathogenesis are discussed.

PMID- 12046592
TI  - Genetic dissection of Ralstonia solanacearum hrp gene cluster reveals that the
      HrpV and HrpX proteins are required for Hrp pilus assembly.
AB  - In both plant and mammalian Gram-negative pathogenic bacteria, type III secretion
      systems (TTSSs) play a crucial role in interactions with the host. All these
      systems share conserved proteins (called Hrc in plant pathogens), but each
      bacterium also produces a variable number of additional type III proteins either
      unique or with counterparts only in a limited number of related systems. In order
      to investigate the role of the different proteins encoded by the hrp gene cluster
      of the phytopathogenic bacterium Ralstonia solanacearum, non-polar mutants in all
      hrp genes (except for hrcQ) were analysed for their interactions with plants,
      their ability to secrete the PopA protein and their production of the Hrp pilus.
      In addition to Hrc proteins and the HrpY major component of the Hrp pilus, four
      additional Hrp proteins are indispensable for type III secretion and for
      interactions with plants. We also provide evidence that hrpV and hrpX mutants can
      still target the HrpY pilin outside the bacterial cell but are impaired in the
      production of Hrp pili, indicating that HrpV and HrpX proteins are involved in
      the assembly of this appendage.

PMID- 12046594
TI  - What's your 'fair' share?

PMID- 12046595
TI  - Physician recruitment. The value of docs.

PMID- 12046593
TI  - Contact--Wired to win. Computer-driven communication.

PMID- 12046596
TI  - Pediatric care. Ahoy, ye patients!

PMID- 12046597
TI  - Multiple chemical sensitivity (MCS) and others: allergological, environmental and
      psychological investigations in individuals with indoor air related complaints.
AB  - Clinical observations point to an expanding group of individuals attributing
      hypersensitivity phenomena to indoor air pollution. It was the aim of this study
      to characterize such subjects by an interdisciplinary approach. Sixty-five
      individuals, recruited by a public campaign, were studied by a thorough
      allergological examination and a structured psychological interview. Measurements
      of common indoor pollutants in the air and in the dust were performed in rooms of
      several selected patients. Forty-two patients (65%) revealed a sensitization to
      common allergens, out of these 32 (49%) to house dust mites. Thirty-eight (58%)
      patients showed a psychosomatic or psychotic disorder. Increased concentrations
      of at least one of the measured indoor air pollutants were found in 11 out of 13
      investigated houses. According to these results, four groups of patients could be
      identified: Seventeen patients (26%) had "classic" allergic diseases treated
      inadequately. In 19 patients (29%) allergic diseases were superimposed by strong
      psychosomatic interactions. An exclusive psychosomatic or psychotic cause of the
      complaints was found in 19 (29%). Ten subjects (16%) had "classic" allergic
      diseases (e.g. allergic rhinoconjunctivitis, urticaria), however, there were
      additional indications of hypersensitivity reactions to components other than
      classical allergens. Patients presenting with hypersensitivity phenomena
      attributed by themselves to indoor air pollution are a heterogeneous group and
      need a diligent work-up including intense allergological examination. The role of
      increased concentrations of indoor air pollutants has to be elucidated further.

PMID- 12046598
TI  - Molecular taxonomy of the suborder Bodonina (Order Kinetoplastida), including the
      important fish parasite, Ichthyobodo necator.
AB  - Ichthyobodo necator is an important fish ectoparasite with a broad host and
      ecological range. A novel method, involving the use of an anesthetic, allowed the
      collection of large numbers of parasites from the skin and gills of hybrid
      striped bass (Morone saxatilis male x M. chrysops female). Genomic DNA from these
      samples was used to amplify and clone the 18S rRNA gene. The 18S rRNA gene was
      similarly cloned from Bodo caudatus, Bodo edax, Bodo saltans, an unidentified
      Bodo species, and Dimastigella trypaniformis. The resulting sequences were
      aligned with other representative kinetoplastid species using pileup and
      similarities in secondary structure. Phylogenetic relationships within the
      suborder Bodonina and representatives of the suborder Trypanosomatina were
      determined using maximum-likelihood statistics. The phylogenetic analyses
      strongly supported the order Kinetoplastida as a monophyletic assemblage
      consisting of at least two major lineages. One lineage consisted exclusively of
      L. necator, indicating that it may represent a new suborder. The second lineage
      consisted of all other kinetoplastid species. This second lineage appeared to
      contain at least 8 bodonine sublineages, none of which correlated with currently
      recognized families. For three sublineages, there was a close correspondence
      between the 18S phylogeny and the classical taxonomy of Dimastigella,
      Rhynchobodo, and Rhynchomonas. In contrast, Bodo and Cryptobia were polyphyletic,
      containing species in two or more sublineages that may represent separate genera.

PMID- 12046599
TI  - Cattle pathogen tritrichomonas foetus (Riedmuller, 1928) and pig commensal
      Tritrichomonas suis (Gruby & Delafond, 1843) belong to the same species.
AB  - A number of reports suggest that the sexually transmitted pathogen of cattle,
      Tritrichomonasfoetus, and a gastrointestinal commensal of pigs, Tritrichomonas
      suis, are very similar and may be co-specific. A conclusive review of the
      taxonomic and nomenclatural status of these species has not been presented so
      far. Toward this end, we reexamined and compared porcine and bovine trichomonads
      with regard to their morphology, pathogenic potential, and DNA polymorphism.
      Using light and electron microscopy, no distinguishing features between T. foetus
      and T. suis strains were found in size, general morphology, and karyomastigont
      structure. Both bovine and porcine trichomonads showed pathogenic potential in
      the subcutaneous mouse assays and did not separate into distinct groups according
      to strain virulence. Three DNA fingerprinting methods (i.e. RFLP, RAPD, and PCR
      based analysis of variable-length DNA repeats) that produce species-specific DNA
      fragment patterns did not distinguish between the bovine and porcine strains.
      Sequencing of a variable 502-bp DNA fragment as well as comparison of 16S rRNA
      gene sequences did not reveal species-specific differences between the cattle and
      porcine strains. Therefore, we conclude that T. foetus and T. suis belong to the
      same species. To prevent confusion that may arise from T. foetus-T. suis
      synonymy, we propose to suppress the older name suis and maintain its accustomed
      junior synonym foetus as a nomen protectum for both cattle and porcine
      trichomonads. The case has been submitted to the International Commission on
      Zoological Nomenclature for ruling under its plenary power.

PMID- 12046600
TI  - Leukemic mantle cell lymphoma can behave in an indolent fashion.

PMID- 12046601
TI  - Leukemic phase and histologic subtypes of mantle cell lymphoma.

PMID- 12046602
TI  - The pathologist's role in the use of human tissues in research--legal, ethical,
      and other issues.
AB  - Because of their central role in examining and storing samples of human tissues
      obtained for diagnosis or therapy of diseases, pathologists frequently are
      involved in providing human tissues for a wide range of research. This is an
      important role for the pathologist that leads to increased understanding of
      disease, to potential methods of prevention, and to improved therapy. Recent
      conferences concerning uses of human tissues in research have indicated that
      there is confusion with respect to legal issues and requirements of pathologists
      who are involved in research with human tissues. This paper discusses current
      federal regulations concerning the use of human tissues and medical information
      in research as specified in Title 45, Part 46 of the Code of Federal Regulations
      (45 CFR 46) "Protection of Human Subjects." The authors also recommend approaches
      that pathologists can utilize to ensure that they are meeting all federal
      regulations with respect to the use of human tissues in research.

PMID- 12046603
TI  - Thyroid function testing: toward efficiency and effectiveness.

PMID- 12046604
TI  - Duplicate laboratory orders: a College of American Pathologists Q-Probes study of
      thyrotropin requests in 502 institutions.
AB  - OBJECTIVE: To examine the frequency and cause of duplicate thyrotropin (TSH)
      testing. METHODS: Five hundred two institutions, ranging in size from fewer than
      100 to more than 600 beds, examined consecutively processed TSH assays to
      identify duplicate orders. Duplicates were defined as two or more TSH tests
      performed within 7 days. All together, participants submitted data on 221,476 TSH
      orders. RESULTS: The median institution reported that 1.5% of TSH tests
      duplicated a TSH order that had been received from the same patient within the
      previous 7 days. Ten percent of institutions reported that 4.5% or more of their
      TSH tests were duplicates. Institutions with higher duplicate rates tended to be
      larger (ie, they had a greater number of occupied beds) and to have duplicate
      tests that were more likely to be ordered by a physician other than the one who
      ordered the initial test. Participants reported that for 19% of duplicate orders,
      physicians were unaware that the first test had been ordered. Physicians also
      indicated that duplicate assays were ordered to see if a previous result had
      changed (15%) or to check on the accuracy of a previous result (13%).
      Participants reported that 11% of duplicate TSH assays that their laboratory
      performed had apparently never been ordered. CONCLUSIONS: A large number of
      institutions are performing duplicate TSH tests that, in most cases, appear to be
      medically unnecessary. Institutions aiming to reduce the frequency of duplicate
      testing should consider policies that decrease the opportunity for different
      physicians to order tests on a single patient and should increase the accuracy
      with which physician orders are transmitted to the laboratory.

PMID- 12046605
TI  - Lung carcinoma surgical pathology report adequacy: a College of American
      Pathologists Q-Probes study of over 8300 cases from 464 institutions.
AB  - OBJECTIVE: To assess the adequacy of reporting gross and microscopic pathologic
      findings of resected lung carcinoma. DESIGN: Q-Probes study following the College
      of American Pathologists format. SETTING: Pathology laboratories, 1991.
      PARTICIPANTS: Four hundred sixty-four institutions. MAIN OUTCOME MEASURES: Rate
      of reporting gross and microscopic features. RESULTS: Information provided in
      over 8300 surgical pathology reports of resected primary lung carcinomas from 464
      institutions was reviewed. Descriptors included gross and microscopic findings.
      The rate of reporting the descriptors from the aggregate sample is listed as
      follows (the corrected rate for those descriptors in which evaluation was not
      applicable are listed in parentheses for each descriptor where appropriate):
      general findings, standard report or checklist used 20.8%, type of procedure
      stated 89.6%, and lobe or lung of origin stated 99.1% (99.5%); gross findings,
      distance of neoplasm from nearest visceral pleura 61.1%, involvement or lack of
      involvement of bronchus 68.7%, presence or absence of involvement of veins 18.3%,
      parenchyma not involved by neoplasm described 80.1% (81.4%), visceral pleural
      surface described 83.0%, tumor size stated 97.2%, and description of regional
      lymph nodes attached to specimen 74.7% (82.7%); and microscopic findings,
      microscopic description 77.6%, histologic type of tumor stated 99.3%, grade of
      carcinoma stated 80.9% (88.7%), presence or absence of lymphatic vascular
      invasion 24.3%, status of lymph nodes stated 89.0% (95.9%), presence or absence
      of venous invasion 22.6%, presence or absence of neoplasm at bronchial margin
      90.8%, presence or absence of neoplasm at vascular margin 30.9%, presence or
      absence of carcinoma in the visceral pleura 64.6% (66.9%), and presence or
      absence of abnormality in nonneoplastic parenchyma 72.8% (74.1%). CONCLUSION: The
      rate of reporting gross and microscopic features varies; recommendations for
      reporting are made and include the use of a standard report form or checklist.

PMID- 12046606
TI  - Adapting mobile robotic technology to intralaboratory specimen transport.
AB  - OBJECTIVE: To evaluate and implement two identical inexpensive robotic vehicles
      for transport of patient specimens within our clinical laboratory. DESIGN: We
      accepted delivery of the first two robotic vehicles produced by a local vendor
      and studied the vehicles for 13 months. The first 4 months of familiarization and
      customization were followed by 9 months of routine use. SETTING: Within the
      specimen-processing, hematology, and chemistry sections of a large academic
      medical center's clinical laboratory, one floor below ground. INTERVENTION: The
      vehicles replaced 1.5 individuals who transported specimens. OUTCOME MEASURES:
      The number of kilometers the vehicles traveled and the number of routes begun,
      completed, not completed, and with unknown status. In addition, we assessed the
      types of problems that occurred, employee satisfaction, and financial payback.
      RESULTS: When used on all shifts for 13 months, the vehicles traveled an average
      of over 2000 routes and 212 km per month. At any one time, at least one vehicle
      was operational. Of the 17 problems that occurred, the most frequent were
      navigational problems caused by obstacles, such as personnel, in the vehicle's
      right-of-way. For 6 of the last 9 months, navigational, mechanical, and
      electronic problems together occurred no more than two or three times per week.
      Financial payback for the vehicles occurred in less than one year. CONCLUSIONS:
      By the end of the study, the robotic vehicles completed 99.4% of their routes.
      Specimen-processing and transport personnel reported the vehicles made their jobs
      easier and improved timeliness of specimen delivery. We anticipate our potential
      savings over 5 years to be approximately $200,000 (US).

PMID- 12046607
TI  - Peripheral blood lymphocyte apoptosis: a clue to the diagnosis of acute
      infectious mononucleosis.
AB  - OBJECTIVE: To describe the morphology and significance of apoptotic lymphocytes
      in peripheral blood smears of patients with acute infectious mononucleosis. To
      our knowledge this has not been previously reported. DESIGN: Peripheral blood
      smears from 27 patients with a positive heterophile antibody test were collected
      and reviewed for the presence of apoptotic lymphocytes. Flow cytometry was
      performed on three cases to document the previously described low expression of
      bcl-2 in lymphocytes in infectious mononucleosis. Four control patient
      populations comprising 80 cases were similarly screened for the presence of
      apoptotic lymphocytes. SETTING: The specimens were collected over a 3-month
      period in two laboratories at our tertiary care hospital; all specimens were
      processed according to a standard protocol. PATIENTS: Young adult military
      recruits and their spouses, military dependent adolescents, and retired military
      personnel. RESULTS: Twenty-four (88.9%) of 27 peripheral blood smears of patients
      with acute infectious mononucleosis contained readily identifiable apoptotic
      lymphocytes. Three (3.75%) of 80 control peripheral blood smears were identified
      with rare apoptotic lymphocytes, all occurring in patients with viral upper
      respiratory infections. CONCLUSIONS: The finding of apoptotic lymphocytes in a
      peripheral blood smear is useful in the differential diagnosis of infectious
      mononucleosis and neoplastic hematolymphoid processes.

PMID- 12046608
TI  - Verrucous herpes virus infection in human immunodeficiency virus patients.
AB  - OBJECTIVE: Two cases of varicella-zoster virus infection that were clinically and
      pathologically verrucous are reported. Although this phenomenon has previously
      been described in the dermatology literature, it has not, to our knowledge, been
      described in the pathology literature. It is important that pathologists are
      aware of these uncommon but histologically distinctive lesions. DATA SOURCES: The
      patients were seen and treated at the Departments of Dermatology of the
      University of Texas Health Science Center at San Antonio and Brackenridge
      Hospital in Austin, Tex. All information was derived from the medical records and
      from the attending physicians. CONCLUSIONS: Verrucous lesions of herpes
      (varicella) zoster virus infection are rare, but they do occur in patients with
      the acquired immunodeficiency syndrome. Clinically, the lesions studied resembled
      ordinary papillomavirus-induced verrucae. Histologically, there was verrucoid
      epidermal hyperplasia and, unlike ordinary lesions of herpes (varicella) zoster,
      very little inflammation of the dermis. Diagnostic multinucleated keratinocytes
      with herpesvirus cytopathic changes were present within the stratum corneum.

PMID- 12046609
TI  - Malignant mesothelioma: immunohistochemistry and DNA ploidy analysis as methods
      to differentiate mesothelioma from benign reactive mesothelial cell proliferation
      and adenocarcinoma in pleural and peritoneal effusions.
AB  - OBJECTIVE: To determine whether malignant mesotheliomas can be differentiated
      from adenocarcinomas and benign reactive mesothelial cells in pleural and
      peritoneal fluids using immunohistochemical analysis in conjunction with DNA
      ploidy analysis. DESIGN: Sixteen cases of malignant mesothelioma, including
      epithelial, sarcomatous, and biphasic types, were collected. DNA analysis using
      flow cytometry and/or image analysis was performed on paraffin-embedded tissue
      from 15 of the mesothelioma cases, as well as on cytospin cell preparations from
      samples of pleural and peritoneal fluids from cases with either cytologically
      proven adenocarcinoma (seven cases) or benign reactive mesothelial cells (seven
      cases). Immunohistochemical studies were done in 15 mesotheliomas, 5
      adenocarcinomas, and 4 benign reactive mesothelial cell effusions. RESULTS: All
      malignant mesotheliomas tested (100%) stained positively for prekeratin, whereas
      stains for carcinoembryonic antigen, B72.3, Leu-M1, and Ber-EP4 were negative.
      Stains vimentin, epithelial membrane antigen, and CA125 were positive in 75%,
      75%, and 25% of cases tested, respectively. Benign reactive mesothelial cell
      cases stained similarly. Adenocarcinomas were more likely to react positively
      with B72.3, Ber-EP4, and carcinoembryonic antigen, and negatively with vimentin.
      DNA analysis showed that all benign cases were diploid, while all adenocarcinomas
      were nondiploid. Fifty-three percent of the malignant mesotheliomas were
      nondiploid. Sensitivity for detection of nondiploidy was greater for image
      analysis than for flow cytometry (100% vs 75%). CONCLUSIONS: B72.3, Ber-EP4,
      carcinoembryonic antigen, and vimentin are useful immunohistochemical markers in
      differentiating malignant mesotheliomas from adenocarcinomas, whereas
      immunohistochemistry does not reliably distinguish malignant from benign
      hyperplastic mesothelial cells. The addition of DNA ploidy studies is useful for
      differentiating the latter two groups.

PMID- 12046610
TI  - Sodium polystyrene sulfonate (kayexalate) aspiration: histologic appearance and
      infrared microspectrophotometric analysis of two cases.
AB  - OBJECTIVE: Sodium polystyrene sulfonate (kayexalate) is a cation-exchange resin
      given enterally for the treatment of hyperkalemia. Aspiration of this material is
      a rare occurrence, but when visualized in the alveolus, it has a characteristic
      microscopic appearance that is virtually diagnostic. In two cases, recognition of
      the characteristic morphology of the foreign material raised the question of
      sodium polystyrene sulfonate. DESIGN: We used infrared spectroscopy to
      demonstrate the presence of this material in lung biopsies of two patients by
      identifying foreign body particles. Histories of the patients were reviewed for
      exposure to sodium polystyrene sulfonate. SETTING: Two lung specimens were
      referred to the Armed Forces Institute of Pathology with an unknown foreign
      material identified within the air spaces. PATIENTS: The lung biopsies were from
      two children, one postterm female infant who died at 3 days of life and a 4-year
      old girl who underwent lung biopsy during surgical repair for tetralogy of
      Fallot. Both patients had received sodium polystyrene sulfonate previously for
      control of hyperkalemia. RESULTS: The lung specimens showed characteristic
      basophilic, amorphous foreign material in airspaces on histologic sections. The
      identity of this material was confirmed by Fourier transform infrared
      microspectrophotometry. CONCLUSIONS: To our knowledge, we report the first two
      cases of sodium polystyrene sulfonate aspiration in children. This material has a
      distinctive morphologic appearance on histologic sections, and its identity can
      be confirmed by Fourier transform infrared microspectrophotometry.

PMID- 12046611
TI  - Estrogen receptor-negative, progesterone receptor-positive breast carcinoma: poor
      clinical outcome.
AB  - OBJECTIVE: The biological significance of breast carcinomas negative (-) for
      estrogen receptor (ER), but positive (+) for progesterone receptor (PR) is
      unclear. It has been proposed that these tumors contain ER whose presence is
      masked in binding assays by endogenous estrogen. We analyzed the clinical outcome
      of 17 patients with ER-PR+ tumors. METHODS: The disease-free and overall survival
      of a series of 300 women with invasive breast carcinoma was followed for 7 to 79
      (median 41) months. RESULTS: The recurrence rate was significantly greater in ER
      PR+ tumors (8/17 [47%]) than in ER+PR+ tumors (27/177 [15%]), and it was similar
      to the high recurrence rate of ER-PR- tumors (21/57 [37%]). The cancer-related
      death rate was 3 1/2 times higher in the ER-PR+ group than in the ER+PR+ group. A
      significant association between ER-PR+ tumors and tumor recurrence or cancer
      related death persisted even after correction for other variables associated with
      poor outcome (eg, tumor size and lymph node involvement). CONCLUSIONS: Estrogen
      receptor-negative, progesterone receptor-positive breast carcinomas are
      biologically different from ER+PR+ tumors and have a poor clinical outcome.

PMID- 12046612
TI  - Splenic involvement in Wegener's granulomatosis.
AB  - OBJECTIVE: A clinicopathologic review of splenic involvement in Wegener's
      granulomatosis. DESIGN: A retrospective case review, spanning a 10-year period,
      identified five patients with Wegener's granulomatosis and splenic involvement.
      SETTING: A large teaching hospital and outpatient clinics. INTERVENTIONS:
      Cytotoxic therapy (cyclophosphamide and corticosteroids), mechanical ventilation
      in respiratory failure, renal hemodialysis in renal failure, and general
      supportive care. RESULTS: Necrotizing granulomatous inflammation and vasculitis
      with fibrinoid necrosis were found in the spleen in one antemortem case. At
      autopsy, two cases demonstrated extensive infarction; microscopic examination
      revealed parenchymal coagulative necrosis, microcalcification, and vascular
      thrombosis, but no evidence of vasculitis. Two other cases showed nonspecific
      changes of diffuse hyalinization of blood vessels, vascular congestion, and
      hemosiderin deposition. CONCLUSIONS: Splenic involvement in Wegener's
      granulomatosis is rarely diagnosed during life, occurs more frequently than once
      thought, and can occasionally lead to considerable morbidity.

PMID- 12046613
TI  - Recurrent crystal-storing histiocytosis of the lung in a patient without a clonal
      lymphoproliferative disorder.
AB  - A 54-year-old woman developed an asymptomatic solitary lung mass, which recurred
      10 years after resection. Both lesions consisted of a localized collection of
      intra-alveolar and interstitial macrophages filled with numerous eosinophilic
      cytoplasmic crystals. The crystals were non-birefringent, periodic acid-Schiff
      negative, and showed polytypic reaction with both kappa and lambda light chains,
      and alpha, mu, and gamma heavy chains. No immunoglobulin gene rearrangements were
      detected. This lesion is consistent with crystal-storing histiocytosis, which has
      been reported in association with plasmacytoma. However, in this case, the
      absence of monotypic immunoglobulin staining within the crystals or the
      surrounding plasma cells, the absence of DNA rearrangements, and the long
      asymptomatic course raise the possibility that this lesion may be reactive.
      Similar lesions are seen in the lungs of mice with immune defects. Crystal
      storing histiocytosis may represent a general reaction pattern to excess
      immunoglobulin.

PMID- 12046614
TI  - Intraductal papillary mucinous neoplasm of the pancreas presenting as acute
      pancreatitis.
AB  - Intraductal papillary mucinous neoplasms are rare pancreatic exocrine tumors with
      distinct clinicopathologic features. They usually present with a long history of
      chronic pancreatitis-like symptoms, which are often associated with weight loss,
      diarrhea, and malabsorption. We report a case of benign intraductal papillary
      mucinous neoplasm with focal squamous metaplasia presenting as acute necrotizing
      pancreatitis. The clinicopathologic features are discussed in a brief review of
      the literature.

PMID- 12046615
TI  - Why greed is good and I go to sleep disappointed every night.

PMID- 12046616
TI  - Patterns of change in mental health status during the first two years of spousal
      bereavement.
AB  - Patterns of change in mental health were identified for 118 recently widowed
      participants using the Integra Outpatient Tracking Assessment, Mental Health
      Index. Change was measured 4 times over the first 2 years of bereavement using a
      cohort sequential design. It was hypothesized that application of the
      psychotherapy phase model would have some use in understanding the various ways
      in which people grieve. The overall pattern of change in mental health was
      similar to that of the psychotherapy dosage and psychotherapy phase models and
      indicated a dramatic change in overall mental health, well-being, and symptoms
      during the beginning phases of bereavement followed by a plateau. At 24 months
      after the death, participants had not attained the same level of mental health as
      the general population. Within limitations of the design and sample, 2
      conclusions were reached: (a) the overall pattern of change in bereavement was
      similar to that of distressed patients receiving outpatient mental health
      services, and (b) the patterns of change for individuals vary, making it
      important to consider clinical characteristics that might account for individual
      differences. These findings help establish an empirical model of grief that has
      use for clinical interventions.

PMID- 12046617
TI  - Death obsession in Egyptian samples: differences among people with anxiety
      disorders, schizophrenia, addictions, and normals.
AB  - Seven groups (n = 765) of Egyptian normals (non-clinical), anxiety disorder
      patients, and patients suffering from schizophrenia (males and females), and
      addicts (males only) were selected. They were generally matched as groups
      according to age, occupation, and education. All participants responded,
      individually, to the Death Obsession Scale (DOS). Cronbach's alpha reliability
      statistics for the 7 groups ranged between .83 and .94, denoting from good to
      high internal consistency of the DOS. The most singular finding is that the
      female and male anxiety disorder patients' means were greatly and significantly
      higher than the means of the other five groups. The other salient differences
      were that female schizophrenics had a significantly higher mean than both male
      normals and male schizophrenics. Male schizophrenics and male normals had,
      respectively, the lowest mean DOS scores. The male addicts had a mean DOS score
      that was less than both male and female anxiety disorder groups. Females have
      higher mean DOS scores than their male counterparts in the normal, anxiety
      disorder patients, and patients suffering from schizophrenia groups

PMID- 12046618
TI  - Teaching thanatology in a foreign country: implications for death educators.
AB  - Although an increasing number of death educators will have the opportunity to
      teach abroad, many may not be fully aware of the issues that arise in
      intercultural instruction and are not prepared to handle the pedagogical
      challenges associated with teaching thanatology in a foreign country. On the
      basis of experience of teaching in China, the author describes the challenges of
      intercultural teaching, strategies for adapting instruction to address the
      pedagogical obstacles, and the ways an international teaching experience can
      enrich instruction.

PMID- 12046619
TI  - Opera subculture and suicide for honor.
AB  - The influence of music-based subcultures on suicidality has been the subject of
      much debate but little scholarly research. While previous work has documented
      that suicide is a remarkably frequent cause of death in opera, it has not
      explored the related consequences on opera's audience. In particular, the
      possible influence of the opera subculture on suicide acceptability has been
      largely unexplored. Suicide in the case of life without honor, the "Madame
      Butterfly Effect," is a theme in opera. Persons who are drawn into and/or
      influenced by the opera subculture of honor are hypothesized to be more accepting
      of suicide in the case of dishonor to one's family. Data are from the national
      general social surveys (N = 845). A multivariate logistic regression analysis
      finds that opera fans are 2.37 times more accepting of suicide because of
      dishonor than nonfans. Only two variables, religiosity and education, are more
      closely related to suicide acceptability than opera fanship. These are the first
      empirical results on the subject of opera and suicide acceptability.

PMID- 12046620
TI  - Bose-Einstein condensation in dilute atomic gases.
AB  - Bose-Einstein condensation is one of the most curious and fascinating phenomena
      in physics. It lies at the heart of such intriguing processes as superfluidity
      and superconductivity. However, in most cases, only a small part of the sample is
      Bose-condensed and strong interactions are present. A weakly interacting, pure
      Bose-Einstein condensate (BEC) has therefore been called the "holy grail of
      atomic physics". In 1995 this grail was found by producing almost pure BECs in
      dilute atomic gases. We review the experimental development that led to the
      realization of BEC in these systems and explain how BECs are now routinely
      produced in about 25 laboratories worldwide. The tremendous experimental progress
      of the past few years is outlined and a number of recent experiments show the
      current status of the field. Electronic supplementary material to this paper can
      be obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00114-001-0277-8.

PMID- 12046621
TI  - Where to find a mate? Resource-based sexual communication of webbing clothes
      moth.
AB  - Mate location in moths typically entails long-range attraction of males to female
      produced pheromone. Here, we show that male and female webbing clothes moths,
      Tineola bisselliella, seek larval habitats (dry carrion, animal lairs, etc) to
      encounter mates. With males seeking, and arriving at, larval habitat earlier at
      night than females, male-produced pheromonal and sonic signals enhance the
      habitat's attractiveness to females. This resource-based mating strategy of T
      bisselliella differs from that known for most other moths. It may have evolved in
      response to larval habitats that are patchy and temporary, but that disseminate
      attractive semiochemicals so abundantly that T bisselliella encounter them more
      readily than their own pheromones.

PMID- 12046622
TI  - A chemical view of the most ancient metazoa--biomarker chemotaxonomy of
      hexactinellid sponges.
AB  - Hexactinellid sponges are often considered to be the most ancient metazoans.
      Lipid biomarkers from 23 species were studied for information on their
      phylogenetic properties, particularly their disputed relation to the two other
      sponge classes (Demospongiae, Calcarea). The most prominent lipid compounds in
      the Hexactinellida comprise C28 to C32 polyenoic fatty acids. Their structures
      parallel the unique patterns found in demosponge membrane fatty acids
      ('demospongic acids') and strongly support a close phylogenetic association of
      the Demospongiae and the Hexactinellida. Both taxa also show unusual mid-chain
      methylated fatty acids (C15-C25) and irregular C25- and C40-isoprenoid
      hydrocarbons, tracers for specific eubacteria and Archaea, respectively. These
      biomarkers indicate a similar, highly conservative symbiont community, although
      some shift in the abundance of the associated microbiota was observed. The lack
      of these features in calcareous sponges further contradicts the still common view
      that Calcarea and Demospongiae are more closely related to each other than either
      is to the Hexactinellida.

PMID- 12046623
TI  - Mutations for activity level in Drosophila jambulina perturbed its pacemaker that
      controls circadian eclosion rhythm.
AB  - Mutations for activity level, designated hpa and hra, in Drosophila jambulina
      altered properties of the pacemaker controlling eclosion rhythm. Entrainment of
      eclosion rhythm was studied in light-dark (LD) cycles of 12:12 h at 28 degrees C.
      The wild type strain entrained to LD cycles but the hpa or hra strain did not.
      When these strains were released from constant light (LL) to constant darkness
      (DD), the wild type strain free-ran while other two strains were arrhythmic.
      Temperature cycles entrained the wild type and hpa strain in DD and LL, and when
      transferred to constant temperature following thermoperiodic entrainment, the
      wild type strain free-ran in DD, while the hpa strain free-ran in LL as if the
      input of LL was essential for its free-running state. Temperature cycles
      entrained the hra strain in DD but not in LL, and free-running rhythmicities were
      never established, suggesting that the hra mutation has altered the basic
      properties of its pacemaker.

PMID- 12046624
TI  - Daughters inherit colonies from mothers in the 'living-fossil' ant Nothomyrmecia
      macrops.
AB  - Newly mated queens of monogynous (single queen) ants usually found their colonies
      independently, without the assistance of workers. In polygynous (multiple queen)
      species queens are often adopted back into their natal nest and new colonies are
      established by budding. We report that the Australian 'living-fossil' ant,
      Nothomyrmecia macrops, is exceptional in that its single queen can be replaced by
      one of the colony's daughters. This type of colony founding is an interesting
      alternative reproductive strategy in monogynous ants, which maximizes fitness
      under kin selection. Successive queen replacement results in a series of
      reproductives over time (serial polygyny), making these colonies potentially
      immortal. Workers raise nieces and nephews (relatedness < or = 0.375) the year
      after queen replacement. Although N. macrops is 'primitive' in many other
      respects, colony inheritance is likely to be a derived specialization resulting
      from ecological constraints on solitary founding.

PMID- 12046625
TI  - Distal mdx muscle groups exhibiting up-regulation of utrophin and rescue of
      dystrophin-associated glycoproteins exemplify a protected phenotype in muscular
      dystrophy.
AB  - Unique unaffected skeletal muscle fibres. unlike necrotic torso and limb muscles,
      may pave the way for a more detailed understanding of the molecular pathogenesis
      of inherited neuromuscular disorders and help to develop new treatment strategies
      for muscular dystrophies. The sparing of extraocular muscle in Duchenne muscular
      dystrophy is mostly attributed to the special protective properties of extremely
      fast-twitching small-diameter fibres, but here we show that distal muscles also
      represent a particular phenotype that is more resistant to necrosis. Immunoblot
      analysis of membranes isolated from the well established dystrophic animal model
      mdx shows that, in contrast to dystrophic limb muscles, the toe musculature
      exhibits an up-regulation of the autosomal dystrophin homologue utrophin and a
      concomitant rescue of dystrophin-associated glycoproteins. Thus distal mdx muscle
      groups provide a cellular system that naturally avoids myofibre degeneration
      which might be useful in the search for naturally occurring compensatory
      mechanisms in inherited skeletal muscle diseases.

PMID- 12046626
TI  - Midgut tissue of male pine engraver, Ips pini, synthesizes monoterpenoid
      pheromone component ipsdienol de novo.
AB  - For over three decades the site and pathways of bark beetle aggregation pheromone
      production have remained elusive. Studies on pheromone production in Ips spp.
      bark beetles have recently shown de novo biosynthesis of pheromone components via
      the mevalonate pathway. The gene encoding a key regulated enzyme in this pathway,
      3-hydroxy-3-methylglutaryl-CoA reductase (HMG-R), showed high transcript levels
      in the anterior midgut of male pine engravers, Ips pini (Say)
      (Coleoptera:Scolytidae). HMG-R expression in the midgut was sex, juvenile
      hormone, and feeding dependent, providing strong evidence that this is the site
      of acyclic monoterpenoid (ipsdienol) pheromone production in male beetles.
      Additionally, isolated midgut tissue from fed or juvenile hormone III (JH III)
      treated males converted radiolabeled acetate to ipsdienol, as assayed by radio
      HPLC. These data support the de novo production of this frass-associated
      aggregation pheromone component by the mevalonate pathway. The induction of a
      metazoan HMG-R in this process does not support the postulated role of
      microorganisms in ipsdienol production.

PMID- 12046627
TI  - Molecular structures and associations of humic substances in the terrestrial
      environment.
AB  - Here we show, for the first time, evidence of the primary molecular structures in
      humic substances (HS), the most abundant naturally occurring organic molecules on
      Earth, and their associations as mixtures in terrestrial systems. Multi
      dimensional nuclear magnetic resonance (NMR) experiments show us that the major
      molecular structural components in the mixtures operationally defined as HS are
      aliphatic acids, ethers, esters and alcohols; aromatic lignin derived fragments;
      polysaccharides and polypeptides. By means of diffusion ordered spectroscopy,
      distinct diffusion coefficients consistent with relatively low molecular weight
      molecules were observed for all the components in the mixtures, and saccharides
      were the largest single class of component present. Liquid chromatography NMR
      confirmed that HS components can be easily separated and nuclear Overhauser
      effect (NOE) enhancements support the finding that the components are of
      relatively low molecular weight <approximately 2,000 Da. The widely recognized
      properties of HS, i.e., characteristics indicative of crosslinked, macromolecular
      networks, can now be explained as aggregation of mixtures, most likely instigated
      by complexation with metal cations.

PMID- 12046628
TI  - Ancient specimens and DNA contamination: a case study from the 12S rRNA gene
      sequence of the "Linh Duong" bovid (Pseudonovibos spiralis).
AB  - In 1993, several unusual horn sheaths, collected in the South of Vietnam, were
      regarded as evidence for a new mammal species, Pseudonovibos spiralis. However,
      the taxonomic status of P. spiralis remains a highly controversial subject:
      firstly, it has been related to three different groups of the family Bovidae:
      Antilopini (gazelles), Bovini (oxen, bisons, and buffaloes), and Caprini sensu
      lato (goats, sheep and allies). Secondly, certain horns have been shown to be
      faked. Most recently, it has been suggested, on the basis of 12S rRNA gene
      sequences, that P. spiralis was a new species of buffalo. I demonstrate here that
      this conclusion was inaccurate, and base this on the grounds that: (1) the
      putative sequence of P. spiralis is shown to be a chimera obtained from three
      different species: Bos taurus, Bubalus bubalis and Saiga tatarica, and (2)
      several factors indicate that the specimen used was not authentic. This new study
      confirms earlier suggestions that the horns used to formally describe P. spiralis
      were bogus and were in fact derived from the horns of domesticated cattle (Bos
      taurus). The data suggest that P. spiralis never existed.

PMID- 12046629
TI  - Nestmate recognition in social wasps: manipulation of hydrocarbon profiles
      induces aggression in the European hornet.
AB  - The influence of individual cuticular hydrocarbons on nestmate recognition in the
      European hornet, Vespa crabro L., was investigated. We observed the behavioural
      response of workers towards differently treated dead conspecifics in a bioassay.
      Dummies were extracted with dichloromethane and extracts were spiked with
      microgram amounts of synthetic hydrocarbons naturally occurring on the cuticle of
      V. crabro. These modified extracts were reapplied to extracted workers that were
      subsequently tested in the bioassay. Non-spiked nestmate dummies (negative
      control) and untreated non-nestmate dummies (positive control) were tested in
      control experiments. The addition of only heneicosane or a mixture of
      heneicosane, tricosane, and (Z)-9-tricosene to the extracts led to a significant
      increase of agonistic behaviour in workers leaving the nest for foraging flights.
      Returning workers reacted much less aggressively than those leaving. This is one
      of the first behavioural proofs that manipulation of cuticular hydrocarbon
      profiles can be perceived by a social insect species. The results support the
      hypothesis that colony-specific cuticular hydrocarbon profiles are involved in
      the phenomenon of nestmate recognition among social insects.

PMID- 12046630
TI  - Trace elements in buried human bones: intra-population variability of Sr/Ca and
      Ba/Ca ratios--diet or diagenesis?
AB  - A comparative analysis of trace element data of human skeletal material from four
      archaeological sites is presented. We show that the state of histomorphological
      preservation of bone, which is a measurement for the degree of its diagenetic
      alteration, closely corresponds to the Sr/Ca and Ba/Ca ratios at an intra
      population level. This study challenges the validity of dietary studies that are
      based on the presently used procedures for sample preparation and subsequent
      evaluation of strontium and barium concentrations.

PMID- 12046631
TI  - Bioproduction strategies for rare hexose sugars.
AB  - A new strategy for the bioproduction of all ketohexoses was developed using
      hexitols as intermediates. Biocatalysts used to employ the strategy were D
      tagatose 3-epimerase, which epimerizes ketohexoses at the C-3 position, and
      oxidoreductases, which catalyze oxidation-reduction reactions between ketohexoses
      and the corresponding hexitols. Arranging all the ketohexoses and hexitols in a
      symmetric ring and connecting them with 20 biochemical reactions, I was able to
      construct a design for the bioproduction of all the rare ketohexoses. Various
      aldose isomerases transform ketohexoses into the corresponding aldohexoses, so
      the strategy is useful for the bioproduction of all the rare hexose sugars.
      Furthermore, the design revealed that there are four routes to the L-hexose world
      from the D-hexose one.

PMID- 12046632
TI  - A secondary copulatory structure in a female insect: a clasp for a nuptial meal?
AB  - Secondary copulatory structures are well-known in male dragonflies and spiders.
      Here I report a secondary copulatory organ in female ground weta, Hemiandrus
      pallitarsis (Ensifera, Orthoptera - crickets and allies). The organ, located on
      the underside of the abdomen, appears to secure the male's genitalia during the
      transfer of a spermatophylax nuptial meal to this location, an area quite
      separate from the female's primary copulatory structures, where the sperm ampulla
      is attached.

PMID- 12046633
TI  - Transient division of labor and behavioral specialization in the ant Formica
      schaufussi.
AB  - Cooperative prey retrieval in the monomorphic ant Formica schaufussi is carried
      out by workers that perform functionally distinct roles which persist only for
      the duration of a single retrieval event. A forager (scout) that locates prey too
      large to retrieve individually organizes cooperative prey transport by recruiting
      nestmates (recruits) to assist in retrieval. The scout and recruit roles appear
      to be determined by whether a worker activates recruitment or is recruited from
      the nest. Scouts organize recruitment and play a key role in maintaining the
      cohesion of the retrieval group. If a scout that has initiated group transport is
      experimentally removed, the recruited workers composing the retrieval group
      typically abandon the prey and cooperative foraging is terminated. In this
      context, recruits are unable to function as scouts and reorganize group
      transport. Individuals marked as recruits in one prey retrieval, however, can
      switch and act as scouts in subsequent retrievals. Because the roles of
      individuals persist within but not between retrieval events, the specialization
      involved in cooperative prey retrieval cannot easily be explained as a response
      associated with age-related or genetic predispositions. This transient division
      of-labor, in which individual roles may persist only for the duration of a single
      group action, represents a novel type of short-term individual specialization.

PMID- 12046634
TI  - Levels of behavioral organization and the evolution of division of labor.
AB  - The major features of insect societies that fascinate biologists are the self
      sacrificing altruism expressed by colony members, the complex division of labor,
      and the tremendous plasticity demonstrated in the face of changing environments.
      The social behavior of insects is a result of complex interactions at different
      levels of biological organization. Genes give rise to proteins and peptides that
      build the nervous and muscular systems, regulate their own synthesis, interact
      with each other, and affect the behavior of individuals. Social behavior emerges
      from the complex interactions of individuals that are themselves far removed from
      the direct effects of the genes. In order to understand how social organization
      evolves, we must understand the mechanisms that link the different levels of
      organization. In this review, we discuss how behavior is influenced by genes and
      the neural system and how social behavior emerges from the behavioral activities
      of individuals. We show how different levels of organization share common
      features and are linked through common mechanisms. We focus on the behavior of
      the honey bee, the best studied of all social insects.

PMID- 12046635
TI  - "As needed" pharmacotherapy combined with stimulus control treatment in chronic
      insomnia--assessment of a novel intervention strategy in a primary care setting.
AB  - Discontinuous, nonnightly hypnotic therapy in the treatment of chronic insomnia
      is likely to offer benefits such as maintained efficacy while preventing
      unnecessary long-term nightly use associated with the risk of tolerance and
      dependence. Based on the favorable results seen in four zolpidem studies using
      increasing degrees of flexibility in drug intake schedule, we developed the
      concept further and investigated "as needed" zolpidem pharmacotherapy amended by
      the optional use of stimulus control in conditions close to the "real life"
      practice. In a prospective, observational open study in 550 primary care settings
      throughout Germany, 2690 patients with chronic insomnia (mean age 59 years, 66%
      female, 50% with pharmacotherapy pretreatment) were treated with zolpidem
      according to an "as-needed" (pro re nata) administration treatment schedule (up
      to five tablets per week, intake nights chosen by the patient), amended by the
      optional use of behavioral therapy (stimulus control) during drug-free nights.
      After the three weeks' treatment period, in two thirds of patients (63%) the
      weekly number of tablets used was reduced in contrast to baseline. The average
      zolpidem tablet number taken decreased by 28% (from 3.7 to 2.6 per week; p <
      0.00001) without any significant impact on the treatment efficacy assessed
      through the CGI. The subjective latency to sleep onset was reduced from a mean of
      74 27 min (p < 0.00001) and total sleep time increased from 5.0 to 6.8 h (p <
      0.00001). Efficacy of treatment was rated as very good or good in 93% by the
      investigators. Adverse events were observed only in 1.2% of patients and were
      generally of mild nature. No serious adverse event occurred. These results
      underline the validity of the zolpidem "as needed" treatment concept. It is
      feasible in a safe and effective manner also in a primary care setting and can be
      amended by stimulus control. Further research is warranted on the contributions
      of both treatment components to effectiveness and on the efficacy and safety
      issues of long-term use.

PMID- 12046636
TI  - A preliminary study of the relationship between clozapine-induced weight gain and
      menstrual irregularities in schizophrenic, schizoaffective, and bipolar women.
AB  - Controversy persists about links between psychotropic drug use, obesity, and
      consequent menstrual irregularities. Although these interrelationships have been
      suggested to possibly explain polycystic ovarian syndrome among women taking
      valproate, less is known about menstrual irregularities associated with weight
      gain caused by other psychotropics. Clozapine, sparing of prolactin-related
      menstrual effects yet often associated with weight gain, offers a model
      psychotropic from which to test such hypotheses. We studied outpatient
      premenopausal women from a clozapine clinic to preliminarily assess the
      association between menstrual cycle patterns and body mass index (BMI). Records
      were reviewed for 13 female premenopausal schizophrenic, bipolar, or
      schizoaffective outpatients who took clozapine with no conventional
      antipsychotics for >6 months. Mean 6-month menstrual cycle lengths were compared
      with BMIs and relative weight changes since starting clozapine. Subjects took
      clozapine (mean +/- SD dose 392.2 +/- 195.7 mg/day) for a mean +/- SD of 4.4 +/-
      3.2 years, with a mean preclozapine weight increase of 27%. Twenty-three percent
      had menstrual irregularities in the preceding 6 months (mean +/- SD cycle length
      = 36.4 +/- 18.1 days), although no significant associations were observed between
      cycle length and (a) mean +/- SD BMI (32.0 +/- 8.4) (r = -0.09, p = 0.78) or (b)
      weight change since starting clozapine (r = -0.10, p = 0.75). The observed lack
      of association between clozapine-induced weight gain and menstrual disturbances
      would provisionally suggest that iatrogenic weight gain does not robustly explain
      the emergence of irregular menses among premenopausal women taking clozapine.

PMID- 12046637
TI  - Somatoform disorders in children and adolescents: a comparison with other
      internalizing disorders.
AB  - A chart review of children and adolescents attending a university-based
      psychiatric outpatient clinic over a 1-year period was done. Nineteen consecutive
      patients with somatoform disorders were compared with 26 consecutive patients
      with other internalizing disorders, i.e., depressive disorders and/or anxiety
      disorders without disruptive behavior problems. Mean age, sex distribution,
      cognitive level, and duration of symptoms were not different between groups. Self
      and parent-reported levels of psychopathology, including depression, anxiety,
      suicidal ideation, and deliberate self-harm, differentiated between somatoform
      disorders and other internalizing disorders at the group level. Levels of
      adaptive functioning and functional somatic symptoms did not. High levels of
      medically unexplained symptoms should prompt the clinician for assessing
      depressive symptoms and anxiety. Findings also support the use of DSM-IV criteria
      in pediatric patients to differentiate somatoform disorders from other
      internalizing disorders.

PMID- 12046638
TI  - Folinic acid (Leucovorin) as an adjunctive treatment for SSRI-refractory
      depression.
AB  - Low folate is associated with poorer response to selective serotonin reuptake
      inhibitors (SSRIs) in major depressive disorder (MDD). Folate supplementation in
      MDD has been studied in other settings with promising results. The objective of
      this study was to assess the efficacy of methylfolate as an adjunctive treatment
      among adults with MDD and inadequate response to an SSRI. Twenty-two adults (59%
      female; mean age 45.2 +/- 11.0 years) with DSM-IV MDD, partial or nonresponse to
      an SSRI after at least 4 weeks of treatment, and a 17-item Hamilton Depression
      Rating Scale (HAM-D-17) score > or = 12 were enrolled in this 8-week prospective
      open trial. Exclusion criteria included current use of anticonvulsants or
      psychotropics other than an SSRI, or B12 deficiency. Leucovorin (folinic acid),
      which is metabolized to methylfolate, was added to SSRIs at 15-30 mg/day. Folate
      levels rose from 28 +/- 19 ng/mL to 301 +/- 203 ng/mL (p < 0.001). HAM-D-17
      scores among the 16 completers decreased from 19.1 +/- 3.9 to 12.8 +/- 7.0 (p <
      0.01). However only 31% of completers and 27% of the intent-to-treat (ITT) sample
      achieved response (> or = 50% reduction in HAM-D-17 scores), and only 19% of
      completers and 18% of the ITT sample achieved remission (HAM-D-17 < or = 7).
      Leucovorin appears to be modestly effective as an adjunct among SSRI-refractory
      depressed individuals with normal folate levels. The application of leucovorin as
      an adjunct in the setting of refractory depression deserves further study.

PMID- 12046639
TI  - Awareness of obesity and weight issues among chronically mentally ill inpatients:
      a pilot study.
AB  - Obesity in psychotic patients is a subject of increasing scrutiny, but there is a
      dearth of data regarding awareness about weight related issues among chronic
      inpatients. To assess this issue state hospital patients voluntarily completed an
      anonymous questionnaire concerning obesity, weight gain variables, concern about
      weight, and methods to control weight gain. Sex, age, weight, and height were
      collected with completed surveys. A total of 128 respondents completed the
      questionnaire of which 85% were male. Respondents' mean age was 39.8 years, mean
      BMI 30.84 kg/m2 with 46.6% obese. There was a significant correlation between BMI
      and awareness of current weight status (p = 0.005), but not between BMI and level
      of concern about weight among all respondents (p = 0.308) or in the obese
      subgroup (p = 0.693). Significantly fewer obese patients indicated no weight
      problem, or no need to control their weight compared to the nonobese (p = 0.004),
      yet only 10% of obese patients requested to be placed on a mandatory monitored
      diet. Chronically mentally ill inpatients thus accurately perceive their obesity
      status, but level of concern does not correlate with BMI, and the obese are
      reluctant to choose mandatory dieting as a remedy. These findings have
      significant implications for programmatic measures to control weight gain among
      chronic inpatients, and for use of atypicals that have a greater propensity to
      cause weight gain.

PMID- 12046640
TI  - Improving outcome in schizophrenia: the potential importance of EPS and
      neuroleptic dysphoria.
AB  - Despite half a century of antipsychotic drug treatment, the outcome of therapy in
      schizophrenia remains disappointing. Relapse, rehospitalization, limited
      fulfilment of social roles, and suicide remain frequent, and the economic costs
      are high. Current relapse rates may be two to three times higher than those that
      could be achieved with optimal use of therapy. Poor compliance with treatment is
      considered to be a significant preventable cause of poor outcome and is in turn
      likely to be influenced by the patient's experience of drug treatment. There is
      some evidence that extrapyramidal symptoms (EPS), particularly akathisia and
      neuroleptic dysphoria, are associated with poor compliance and poor treatment
      outcome. Atypical antipsychotics have a lower risk of EPS than do standard
      antipsychotics. Some (risperidone, olanzapine, and ziprasidone) show evidence of
      a dose-related increase in EPS, but clozapine and quetiapine have demonstrated a
      placebo-level incidence of EPS across the dose range. Quetiapine does not require
      the regular blood monitoring mandated for clozapine, and results from a patient
      survey indicate a high degree of patient satisfaction with treatment. While
      further research is needed, it is possible that wider use of medications with low
      EPS and high patient acceptability could promote better compliance and improve
      the outcome of schizophrenia treatment.

PMID- 12046641
TI  - Phenomenology of and risk factors for new-onset diabetes mellitus and diabetic
      ketoacidosis associated with atypical antipsychotics: an analysis of 45 published
      cases.
AB  - Case reports and small retrospective studies suggest that atypical antipsychotic
      agents may be associated with new-onset Type II diabetes mellitus (DM) or
      diabetic ketoacidosis (DKA); however, these reports often provide limited or no
      information on demographic variables such as age, gender, ethnicity, relationship
      to weight gain, and time course. We analyzed 45 published cases of new-onset DM
      or DKA for which followed initiation of atypical antipsychotic treatment. Of the
      45 patients, 20 had received clozapine, 19 olanzapine, 3 quetiapine, and 3
      risperidone. Eighty-seven percent patients were male, and 47% African American.
      Forty-two percent of these patients presented as DKA, and 50% manifested no
      weight gain at time of presentation with DM or DKA, although 84% were overweight
      before antipsychotic therapy. Eighty-four percent presented within 6 months and
      59% within 3 months of commencing atypical antipsychotics. The DKA cohort had
      significantly younger age, less overweight at baseline, and higher proportion of
      women than did those with DM alone, without significant differences in
      distribution of ethnicity, weight gain, family history of DM, or duration of
      exposure to atypical agents. Clinicians should be aware of the potential risks of
      new-onset DM and DKA in patients taking atypical antipsychotics, and utilize
      appropriate clinical and laboratory monitoring to prevent serious adverse events.

PMID- 12046642
TI  - A pilot placebo-controlled study of fluvoxamine for pathological gambling.
AB  - The objective of this study was to evaluate the efficacy of fluvoxamine in the
      treatment of pathological gambling. Thirty-two patients were treated for 6 months
      in a double-blind, placebo-controlled study of fluvoxamine 200 mg/day. Outcome
      measures included reduction in money and time spent gambling per week.
      Longitudinal mixed effects models and completers analyses were used for
      estimation and hypothesis testing. Fluvoxamine was not statistically
      significantly different from placebo in the overall sample. However, fluvoxamine
      was statistically significantly superior to placebo in males and in younger
      patients. The power of the study was limited by the high (59%) placebo-response
      rate. Fluvoxamine may be a useful treatment for certain subgroups of patients
      with pathological gambling. Several methodological recommendations are made for
      future pharmacological trials of pathological gambling.

PMID- 12046643
TI  - The effects of industrial and agricultural practices on atmospheric chemistry and
      climate during the anthropocene.

PMID- 12046644
TI  - Abatement of gas-condensate hydrocarbons in a natural wetland.
AB  - Results of a five-year research study on natural attenuation processes in a
      wetland, located downgradient of a sour gas processing plant in central Alberta,
      Canada, show that natural attenuation may present a favourable remedial solution.
      Both free-phase and dissolved phase condensate have been discharging to the
      wetland since 1984. This condensate is primarily composed of C5 to C12
      hydrocarbons, including BTEX compounds. The condensate enters the base of the
      wetland at 1 m below ground surface, resulting in contamination of the wetland
      peat and underlying clay till. The lateral extent of contamination in the wetland
      has remained stable, and apparent free product thickness and BTEX concentrations
      have decreased over time. Sorption, aerobic biodegradation, volatilization, and
      anaerobic biodegradation were identified as active attenuation processes at this
      site. Sorption and desorption processes were evaluated by laboratory testing of
      site soils using 14C-benzene. Linear sorption coefficients (Kd) for the surface
      and subsurface peat were similar (4.48-4.62 l/kg), while the Kd for the
      underlying silt was 0.096 l/kg. The significantly higher Kd values for the peat
      are attributed to the peat's higher organic content (40%), relative to the clayey
      silt (1%). No significant resistance to desorption was observed, however,
      indicating that benzene would remain mobile and bioavailable over time. Aerobic
      biodegradation and volatilization appear to be the main removal processes. They
      are enhanced by a seasonal drop in the water level from surface down to 1 m
      depth, resulting in an aerobic unsaturated zone. Respiration testing in the peat
      indicates a significant aerobic biodegradation rate of 27 mg/kg/day, equating to
      an estimated hydrocarbon removal rate of 5 kg/day across the 3600 m2 plume area.
      Surface vapour measurements indicate hydrocarbon volatilization is occurring at a
      rate of 3 x 10(-4) kg/m2/day, equating to a mass removal of 1 kg/day across the
      plume. Anaerobic biodegradation is occurring primarily in the clayey silt, based
      on geochemical indicator parameters, microbial analyses, and soil vapour
      sampling. Overall, natural attenuation appears to be a feasible remedial solution
      for this wetland, by providing continued removal and degradation of condensate
      components before they reach the downgradient surface water receptor.

PMID- 12046645
TI  - Volatile fatty acids as electron donors for the reductive dechlorination of
      chloroethenes.
AB  - Uses of a mixture of six volatile fatty acids (VFAs) including acetic, propionic,
      butyric, isobutyric, valeric and isovaleric acids as electron donors for the
      reductive dechlorination of chloroethenes have been investigated by both
      microcosm and column studies. The fates of tetrachloroethene (PCE), cis
      dichloroethene (cis-DCE) and vinyl chloride (VC) in the presence of VFAs and in
      the absence of VFAs were respectively documented. The results showed that VFAs
      stimulated complete reductive dechlorination of chloroethenes, either as direct
      substrates for the dechlorinating bacteria or via H2 formed during VFAs
      degradation. There were sequential utilizations of different VFAs by fermenting
      bacteria. In the microcosm, propionic acid was the first to be used, followed by
      acetic, butyric, isobutyric, valeric, and isovaleric acids, and their mean first
      order degradation rates obtained were 0.128, 0.048, 0.016, 0.027, 0.025 and 0.003
      day(-1), respectively. In the column, propionic acid was the first to be used,
      followed by butyric and valeric acids, and their calculated first-order
      degradation rates were 0.833, 0.403 and 0.260 day(-1), respectively.

PMID- 12046646
TI  - Distribution and transportation of polycyclic aromatic hydrocarbons in suspended
      particulate matter and surface sediment from the Pearl River Estuary.
AB  - Based on the quantitative and qualitative analysis of sixteen Polycyclic Aromatic
      Hydrocarbons (PAHs) with GC and GC-MSD, the concentrate distribution and
      transportation characteristics of PAHs in suspended particulate matter (SPM) and
      surface sediments (SS) from the Pearl River Estuary were studied. Whether in SPM
      or in SS, the concentration distribution of PAHs were characterized by
      acenaphthene (mean 55.5 microg/g in SPM, 226 ng/g in SS) with subordinate amounts
      of the tri- and tetra-cycle PAHs such as fluorene, fluoranthene, phenaphene and
      pyrene. However, PAHs had different composition and concentration in SPM and SS.
      Pentacyclic PAHs appeared in SS and seldom in SPM because of their low solubility
      and high molecular weight. The concentrations of the tri-, tetracyclic PAHs in
      SPM were 100-300 times higher than those in SS. The total PAHs varied from 12-281
      microg/g (mean 77 microg/g) in SPM and 208-1849 ng/g (mean 537 ng/g) in SS
      respectively. There were similar correlations between the concentrations of PAHs
      in SPM and salinity, and between the distance of the stations from the river
      outlet moving seawards and the concentrations of PAHs. These indicated that PAHs
      were degraded or transported along with the salinity gradient in SPM and the
      distance from the river outlet in SS. It was also suggested that the sources of
      these PAHs are from sewage and shipping discharge-pollutants. Pearl River Estuary
      had been lightly contaminated by PAHs.

PMID- 12046647
TI  - Distribution and speciation of heavy metals in surface sediments from Guanting
      Reservoir, Beijing.
AB  - Surface sediments in Guanting reservoir of Beijing were studied to evaluate the
      heavy metal pollution. The concentrations of heavy metals lie in the sequence: Zn
      > Pb > Cr > Cu > Ni > Co > Mo > Cd. Significant relationship (p<0.01) between the
      elements Cr, Ni, Co, Cu and Ni indicates that they derived from a common
      geological origin. While the elements Zn, Pb and Cd correlate each other.
      Speciation analysis showed that most of the elements were found in the residual
      fraction. Enrichment of the elements Zn, Pb and Cd were found in the entrance of
      the rivers to the reservoir and the sampling site close to the dam. The sediment
      size-dependent distribution and their speciation distribution in these two sites
      are also distinctly different from other sediment sites. All these may indicate
      potential pollution of elements Zn, Pb and Cd in Guanting reservoir.

PMID- 12046648
TI  - Diurnal variations of aerosol chemical compositions and related gaseous
      pollutants in Beijing and Guangzhou.
AB  - A new apparatus, Steam Jet Aerosol Collector (SJAC) combined with on-line Mobile
      Ion Chromatograph provides a reliable way to measure both aerosol components and
      related gas species simultaneously. The SJAC was applied in the field campaigns
      in Beijing and Guangzhou to investigate aerosol chemical compositions and related
      gaseous pollutants. The concentration levels and diurnal variations are
      discussed, which implies differences in atmospheric chemistry of gas-to-particle
      conversions in Beijing and Guangzhou.

PMID- 12046649
TI  - Adjusted active carbon fibers for solid phase microextraction.
AB  - Adjusted active carbon fiber (AACF) was evaluated for Solid Phase Microextraction
      (SPME), which showed higher sensitivity and stability than traditional coating
      fibers. The characteristics of AACF result from two different activation methods
      (chemical and water vapor) and from variable activation conditions (temperature
      and time). The fiber treated by water vapor appears to have stronger affinity to
      polar compounds, while that treated by chemical activation appears to have
      stronger affinity to non-polar compounds. For different target compounds ranged
      from non-polar to polar, AACF design could be effective with specific selections
      and sensitivities. As applications in this paper, benzoic acid in soy sauce was
      extracted onto water-vapor-activated-fiber, then analyzed using gas chromatograph
      mass spectrometer (GC-MS). The chemical-activated-fiber SPME was applied in the
      analysis of benzene series compounds (BTEX) in water matrix. Compared with
      standard carbon disulfide extraction method, chemical-activated-fiber SPME is
      more convenient due to its simple process and turns to be of relative low
      detection limits.

PMID- 12046650
TI  - Persistent organic pollutants (POPs) in surface sediments of Donghu Lake, Wuhan,
      Hubei, China.
AB  - Surface sediment samples from five different sites were collected in Donghu Lake,
      Wuhan City, Hubei Province, China during November 2000. Over 180 organic
      chemicals were detected using GC-MS controlled by a Hewlett Packard Chemstation
      after soxhlet extraction. Derivatives of benzene, phthalate esters, PAHs,
      phenols, isophorone as priority pollutants or endocrine disruptors, respectively,
      were detected. The concentration of organic pollutants were found to be highest
      at the sampling site located at Southwest Donghu Lake (Shuiguo), caused most
      probably by the untreated wastewater discharge, average at the southern and
      lowest at the northern part of the lake.

PMID- 12046651
TI  - Disrupting effects of polychlorinated biphenyls on gonadal development and
      reproductive functions in chickens.
AB  - Polychlorinated biphenyls (PCBs) are worldwide persistent pollutants that have
      produced detrimental effects on endocrine function and reproduction in a variety
      of species. The present study revealed effects of PCBs on gonadal development and
      functions in chickens of different ages. Aroclor 1254 (0-100 microg/egg) was
      injected into Hyline chicken eggs before incubation. The adult chickens received
      Aroclor 1254 by gavage (50 mg/kg BW). It was observed that in day 5 embryos, PCBs
      resulted in a dose-dependent decrease of primordial germ cell (PGC) numbers, and
      caused PGCs pyknosis and vacuolation. Clomiphen failed to block the effects of
      PCBs. In the newly hatched chicken, PCBs induced a marked decrease in area of the
      transverse sections, diameter and relative area of the testicular tubules. The
      differentiation of germ cells was retarded after PCB treatment. In contrast, the
      area of the left ovarian transverse sections, the thickness of ovarian cortex and
      the number of oocytes increased dramatically in the female chickens after PCB
      exposure. In the adult chickens, PCBs caused no significant changes in body
      weight, respiration, heart rate, body temperature, red and white blood cell
      number, but induced a marked decrease in the testicular weight, and severe damage
      of the seminiferous tubules. The number of the spermatogenic cells and serum
      testosterone level were decreased significantly by PCBs. On the contrary, in the
      laying hens there was no significant effect of PCB on egg quality except a slight
      decrease in egg weight. These results indicated that PCBs exerted its disrupting
      effects on chicken reproduction with a sex and stage-related pattern, and in vivo
      disruption of gonadal development represents a possible model for risk assessment
      of environmental endocrine disrupters by in ovo treatment.

PMID- 12046653
TI  - Bioconcentration of trace organochlorine pesticides by the rainbow trout.
AB  - Bioaccumulation of five organochlorines pesticides [lindan, aldrin, heptachlor
      epoxide, 4,4'-dichloro-diphenyl-trichloroethane (DDT) and hexachlorobenzene
      (HCB)] by the rainbow trout was studied in a laboratory continuous flow system at
      concentration level more closing to that in natural environment (ca. 2 microg/l).
      Under such conditions, bioconcentration kinetics of all the pesticides by the
      rainbow trout was almost linearly increased during the exposure period of 20 days
      for tested chemicals, excepting for lindan. For lindan, approach of an asymptote
      in curve (wet weight basis) could be observed at the end of exposure. The
      concentration factors (CFs) of the five pesticides based on whole body weight
      were in the range of 1000-7000. The difference in CFs may be attributed to the
      octanol water partition coefficients (Kow), size and steric effects of the
      chemicals. The result showed that the bioconcentration kinetics was different
      from those steady states at relatively high concentration in short period.
      Rainbow trout was a suitable kind of fish to study the concentration of organic
      pollutants for it's rather low base value, sensitive and easy to be treatment.
      Difference profile between the water and rainbow trout indicated that measurement
      of total concentration of pesticides in water is insufficient to assess
      bioavailability and toxicity of the organic pollutants to organisms.

PMID- 12046652
TI  - Toxicological effects of the herbicide oxyfluorfen on acetylcholinesterase in two
      fish species: Oreochromis niloticus and Gambusia affinis.
AB  - The alterations of the AChE activity in the brains of two fresh water fishes;
      Oreochromis niloticus and Gambusia affinis were measured after exposure to acute,
      sub-acute and chronic concentrations from the widely used herbicide; oxyfluorfen.
      Bioassays were conducted under controlled laboratory conditions. The used
      concentrations were acute: LC50 for 6 days, sub-acute 1/3 LC50 for 15 days and
      chronic 1/10 LC50 for 30 days. The obtained results showed marked inhibitory
      effects of the herbicide on the activity of AChE in both fishes. However, these
      effects were more pronounced in O. niloticus where the decline in the enzyme
      activity ranged from 19.7 to 81.28% while in case of G. affinis it ranged from
      5.7 to 36.7%. These findings demonstrate that G. affinis is most tolerant to
      oxyfluorfen toxicity compared with O. niloticus.

PMID- 12046654
TI  - The patterns of Cd-binding proteins in rice and wheat seed and their stability.
AB  - The protein-binding forms of cadmium in polluted rice and wheat seeds and their
      stability were investigated using the methods of Sephadex chromatography. Three
      absorption peaks (F-I, F-II and F-III) were identified in Tris-HCl extraction of
      rice and wheat on Sephadex G 75. The Cd in the protein extracts from rice and
      wheat seeds was distributed mainly in the fractions of F-I and F-III. The
      apparent molecular weights of Cd-binding proteins for F-I and F-III were 54.5 and
      5.5 KD, respectively. The components of amino acid for the protein bound with
      heavy metals were different. There were high contents of glutamic acid, cysteine,
      valine, isoleucine, leucine and tyrosine in the protein extracts of rice and
      wheat. After cooking, the Cd-binding proteins were destroyed. High molecular
      weight protein-binding form (54.5 KD) was broken into low molecular weight
      complex (5.5 KD) or tiny peptide chain. Simultaneously, Cd bound with protein was
      released, or mainly bound with protein of smaller molecular size. Enzyme
      treatment (pepsin and trypsin) also caused a destruction of Cd binding protein
      and a change in the distribution of Cd in the eluent. The concentrations of Cd in
      the elution of first and third peak decreased markedly, and the Cd distribution
      was observed in the elution after third peak (F-III).

PMID- 12046655
TI  - Effect and mechanism of inorganic carbon on the biodegradation of dimethyl
      phthalate by Chlorella pyrenoidosa.
AB  - The effect and mechanism of inorganic carbon (IC) on the biodegradation of
      dimethyl phthalate (DMP) by a green microalga Chlorella pyrenoidosa was
      investigated. It was indicated that DMP could be used as the sole carbon source
      to support the slow heterotrophic growth of C. pyrenoidosa, but both the growth
      of C. pyrenoidosa and the biodegradation rate of DMP were obviously increased
      when initial inorganic carbon concentration (IC) was increased from 0.6 to 23.7
      mg/l. Phthalic acid (PA) was found to be an intermediate product of DMP
      biodegradation and accumulated in the culture solution, which caused a sharp
      decrease in pH of medium and inhibited both the growth of alga and the
      biodegradation of DMP. The role of IC for improving the biodegradation of DMP was
      both to supply a favorite carbon source to support the rapid growth of alga and
      to mitigate the decrease of pH because of the production of PA. A suggested
      second-order kinetic equation of organic pollutant biodegradation by microalgae (
      dC/dt = KNr) fitted well with the experimental data and the correlation
      coefficients were all above 0.9. The second-order constant (K) apparently
      declined with the increase of initial IC because lower ratio between organic
      carbon from DMP and IC was used to support the growth of alga when initial IC
      increased.

PMID- 12046656
TI  - Quantitative structure-activity relationships for the toxicity of nitrobenzenes
      to Tetrahymena thermophila.
AB  - In this study IGC50 (50% inhibitory growth concentration) values of 26
      nitrobenzenes were determined for population growth endpoint of Tetrahymena
      thermophila. The toxicity order of the observed compounds has been found as
      follows: dinitro compounds > mono-nitro compounds; dichloronitrobenzenes >
      monochloronitrobenzenes; and meta-substituted nitrobenzenes > ortho-/para
      substituted nitrobenzenes (NT, NPh, NAnis) except for the dinitrobenzenes and
      nitroanilines (DNB, NAn). Quantitative structure activity relationships (QSARs)
      were developed using log of the inverse of the IGC50 (logIGC50(-1)) in mole liter
      as the dependent variable and six molecular descriptors--logP, 1X(V), I, K alpha,
      sigma sigma- and E(LUMO) as the independent variables. Through multiplicate
      regression analysis, one best equation was obtained: log IGC50(-1) = 2.93 +
      0.830sigma sigma- + 0.350I, n = 26, r = 0.923, r2 = 0.852, s = 0.265, f = 66.4
      The equation was used to estimate IGC50 for seven analogues.

PMID- 12046657
TI  - QSAR study on the joint toxicity of 2,4-dinitrotoluene with aromatic compounds to
      Vibrio fischeri.
AB  - The individual and joint toxicities of binary mixtures of 2,4-Dinitrotoluene (2,4
      DNT) and 8 nitrobenzenes and anilines to V. fischeri were determined respectively
      and their mixture toxicity effects were assessed using the Additivity Index (Al).
      The energy of the lowest unoccupied molecular orbital (E(LUMO)) of studied
      compounds was calculated and was used to develop QSARs. The prediction models for
      the individual and mixture toxicity data were respectively: log 1/EC50=3.213
      0.716 E(LUMO), n=9, r=0.830, s=0.545 and log 1/EC50=3.672-0.882 E(LUMO), n=8,
      r=0.925, s=0.406. The joint toxic effects derived from AI values show that the
      mixture toxicity of 2,4-DNT and the other nitrobenzenes is synergistic (AI>0),
      whilst the mixture toxicity of 2,4-DNT and the anilines is antagonistic (AI<0).
      These results confirm that the mixture toxicity is mainly related to
      intracellular oxidation and reduction. -E(LUMO) values of nitrobenzenes are
      higher. The nitrobenzenes when mixed with 2,4-DNT make the mixture systems easily
      reduced; the mixture toxicity effect is synergism. On the other hand, -E(LUMO)
      values of anilines are lower. The anilines when mixed with 2,4-DNT can make the
      mixture systems less easily reduced, and the mixture toxicity effect is
      antagonism.

PMID- 12046658
TI  - The emission soot of biomass fuels combustion as a source of endocrine
      disrupters.
AB  - Emissions of biomass fuel combustion in residential stove from Chinese
      countryside were analyzed to determine the endocrine disrupters by using
      recombinant yeast bioassay. The results showed that there were significant
      steroid modulating activities found in combustion soot of five kinds of biomass
      fuels, which were wood, crop residue, grass, bush and rice straw. The steroid
      activities in the different sub-fractions from chromatographic separation were
      also determined, and the results indicated that polar fraction extracted by
      methanol and aromatic fraction extracted by benzene had relatively high steroid
      activities, and aliphatic fraction almost had no activity. The GC/MS results
      showed that polycyclic aromatic compounds and their derivatives, substituted
      phenolic compounds and their derivatives, aromatic carbonyl compounds, and higher
      molecular weight alcohols and ketones may be the main steroid disrupters in these
      soots.

PMID- 12046659
TI  - Study on the screening of molecular structure parameter in QSAR model.
AB  - Based on the analysis of information flow through the Artificial Neural Network
      (ANN), a new screening rule of the molecular structure parameter in Quantitative
      Structure-Activity Relationship (QSAR) was presented by comparing of the values
      of connection weights and biases of the ANN model. The result showed that model
      quality and prediction ability of QSAR model, which was constructed by screening
      structural parameter with ANN, were better than by the method with MLR. The
      method established the foundation for further study in the mechanism research of
      the bio-toxicity of organic chemicals.

PMID- 12046660
TI  - Responses of legume and non-legume crop species to heavy metals in soils with
      multiple metal contamination.
AB  - Field and glasshouse investigations were conducted on the responses of two
      legumes (field pea and fodder vetch) and three non-leguminous crops (maize, wheat
      and rapeseed) to the heavy metals Cd, Cr, Zn, Pb, Cu and Mn in soil with multiple
      metal contamination. In general, the results indicate that the two legumes and
      wheat were more susceptible to soil metals than were rapeseed and maize. The dry
      matter yields of field pea, wheat, fodder vetch, rapeseed and maize decreased by
      up to 169, 123, 113, 93 and 68%, respectively, in metal-contaminated soil. Among
      the crops, maize had the highest concentrations of Mn, Zn and Cd, rapeseed had
      the highest concentrations of Cr, the concentration of Cu was highest in fodder
      vetch, and wheat was the highest accumulator of Pb. The bioconcentration factors
      (BCF) of the metals decreased as the soil metal loading rates increased except
      for Cr in fodder vetch and Cd in wheat, whose BCF increased as the metal loading
      rate increased. Significant linear correlations were found between plant and soil
      metal concentrations. Patterns of metal distribution in plant parts varied with
      different crops and metals, with more Cd and Cu accumulating in the grain of
      wheat than of maize, suggesting that growing wheat would represent a higher risk
      of food contamination than growing maize in Cd- or Cu-contaminated soil. The
      results suggest that on sites with multiple metal contamination, growing maize
      and rapeseed would be safer than growing wheat or legumes. However, maize could
      perhaps be used for phytoremediation of lightly contaminated soils, providing
      that the crop residues were safely disposed of.

PMID- 12046661
TI  - An innovative Ti/Tio2 mesh photoelectrode for methyl orange photoelectrocatalytic
      degradation.
AB  - A new type of photoelectrode was innovated by anodising titanium mesh in H2SO4
      solution and named Ti/TiO2 mesh electrode. The structural and surface morphology
      of the Ti/TiO2 mesh was examined by X-ray diffraction, Laser Raman spectra and
      scanning electronic microscopy (SEM). The results indicated that its crystal
      structure, morphology and the size of pore were affected greatly by the
      anodisation voltage, current density. The photoelectrocatalytic (PEC) oxidation
      of methyl orange (MO) solution using the Ti/TiO2 mesh was investigated. The
      results demonstrated that Ti/TiO2 mesh prepared at 160 V and 110 mA cm(-2) had
      the best PEC activity. The PEC oxidation efficiency could be significantly
      enhanced by applying an optimal electrical bias voltage between the working
      electrode and counter electrode. It was found that the best performance of PEC
      oxidation was achieved by applying an electrical bias of 0.6 V. It is suggested
      that the recombination of electrons and holes was hindered owing to applying
      electrical bias voltage.

PMID- 12046662
TI  - Photocatalytic detoxification of microcystins combined with ferrate pretreatment.
AB  - This work focuses on the development and evaluation of a combined technique
      including ferrate oxidation and photocatalytic detoxification of microcystins.
      Greater removal efficiency of the microcystins-LR (MLR) can be achieved using the
      combined process. The experimental result demonstrates that the residual Fe after
      ferrate oxidation can enhance the efficiency of photocatalytic reaction. The
      optimal dosage of ferrate 20 mg/l was determined by studying the degradations of
      total organic carbon (TOC) and MLR at different concentrations of residual Fe. As
      expected, pH had a remarkable influence on the reaction rate of detoxification of
      MLR and a low pH was beneficial to the reaction.

PMID- 12046663
TI  - Denitrification of drinking water by a combined process of heterotrophication and
      electrochemical autotrophication.
AB  - A combined two-step process of heterotrophic and electrochemical autotrophic
      denitrification was developed for the treatment of nitrate-contained drinking
      water. The water was first treated with heterotrophic biological denitrification
      and was further purified with electrochemical autotrophic denitrification. The
      two steps were carried out in a heterotrophication-electrochemical
      autotrophication combined reactor (HEAR). The lower section performed as the
      heterotrophic biological reactor and the upper section acted as the
      electrochemical autotrophic reactor. The bioreactor was a packed bed of
      anthracite particles, and the water flow was directed in an upward continuous
      mode. The total nitrate and nitrite concentration, and residual methanol in the
      effluent were monitored to evaluate the performance of the reactor. The reactor
      was operated for one year with a feed concentration of 40 mg NO3(-)-N/l. There
      was no nitrite or residual methanol accumulation in the effluent when the feed
      C:N ratios (m/m) varied from 2.2 to 2.9. However, slightly excessive methanol
      dosage could increase the denitrifying capacity of the reactor. The maximum
      denitrification load of the reactor at 24 degrees C was 10.68 g NO3-/m3 h (47 g
      NO3-) at C:N = 2.5.

PMID- 12046664
TI  - Influence of supplemental nutrient on aerobic decolorization of acid red 14 in
      activated sludge.
AB  - Azo dyes are non-biodegradable in the textile effluent under aerobic condition.
      This study demonstrates that the addition of nutrients leads to degradation of a
      selected azo dye (AR14), and the major decolorization kinetic pathway of AR14
      could be expressed as a pseudo first order kinetic model under the experimental
      conditions used in this study. An excellent correlation was obtained between the
      decolorization speed and additional nutrient concentration, as indicated by a
      coefficient of determination (r2) of 0.9899. At a higher nutrient concentration,
      the relatively high color removal rate can be reached up to 92.9% in a short
      time. The degradation ability of azodye could be changed by supplemental
      nutrient. The destroy of chromophore was the first step of degradation of azo dye
      under the aerobic conditions, and the intermediates of the dye had significant
      toxic to the activated sludge, while AR14 of 150 mg/l had slight inhibitory
      effect on sludge respiration.

PMID- 12046665
TI  - Photocatalytic decomposition of toluene by TiO2 film as photocatalyst.
AB  - This paper reports on the degradation of gaseous toluene by the photocatalytic
      oxidation process. The photocatalyst, TiO2 film, was prepared by the sol-gel
      method and was coated on porous nickel. The photocatalytic decomposition of
      toluene was carried out in a recirculating batch reactor. The factors that affect
      toluene decomposition were studied, including particle size of the catalyst,
      initial toluene concentration, flow rate of toluene in the reactor, relative
      humidity and reactive temperature. In addition, deactivation of the catalyst is
      also discussed. The experiment results showed that toluene can be decomposed
      effectively by the photocatalytic oxidation process, and that toluene degradation
      obeys the first-order reaction.

PMID- 12046666
TI  - Understanding of hazardous waste incineration through computational fluid
      dynamics simulation.
AB  - Rotary kiln incinerators are widely used in the incineration of hazardous wastes
      of various types. However, the complex transport and chemical processes within
      the kiln system are still not well understood. The complete destruction of
      hazardous compounds depends very much on gas mixing behavior of different air and
      waste streams, the distribution of gas temperature and residence time within the
      kiln and the secondary combustion chamber (SCC). Due to large variations of waste
      types and difficulties in feed characterization (physical, chemical and thermal
      properties), the incineration process meets great challenges in a smooth
      operation, with substantial fluctuations of gas temperatures within the system.
      The temperature fluctuations lead to uncertainties in the process chemistry and
      difficulties in emission control. The newly enforced regulations from the
      European Union with stricter emission levels require a better understanding of
      the incineration process and improved process control for lower emissions and a
      better environmental impact. In order to get better understanding of the
      incineration process within the rotary kiln system, research was carried out to
      study the kiln behavior in relation to better process control. One of the focuses
      was on the process simulation by using Computational Fluid-dynamics (CFD) to
      characterize gas flow, temperature distribution and waste combustion in the
      rotary kiln incinerator. Temperature measurement of the operating rotary kiln
      incinerator at AVR-Chemie, located at the Rotterdam harbor in The Netherlands,
      was conducted to validate the CFD model and to provide the information to kiln
      operators at AVR. This paper will address the environmental issues related to the
      hazardous waste incineration, and summarize the results from the current research
      project for the simulation of gas flow and mixing, combustion heat transfer, and
      new ideas to use CFD simulation results for process control of an incineration
      plant.

PMID- 12046667
TI  - Ozonation of the purified hydrolyzed azo dye Reactive Red 120 (CI).
AB  - The combination of chemical and biological water treatment processes is a
      promising technique to reduce recalcitrant wastewater loads. The key to the
      efficiency of such a system is a better understanding of the mechanisms involved
      during the degradation processes. Ozonation has been applied to many fields in
      water and wastewater treatment. Especially for effluents of textile finishing
      industry ozonation can achieve high color removal, enhance biodegradability,
      destroy phenols and reduce the COD. However, little is known about the reaction
      intermediates and products formed during ozonation. This work focuses on the
      oxidative degradation of purified (>90%), hydrolyzed Reactive Red 120 (Color
      Index), a widely used azo dye in the textile finishing processes with two
      monochlorotriazine anchor groups. Ozonation of the dye in ultra pure water was
      performed in a laboratory scale cylindrical batch reactor. Decolorization,
      determined by measuring the light absorbance at the maximum wavelength in the
      visible range (535 nm), was almost complete after 150 min with an ozone
      concentration of 12.8 mg/l. The TOC/TOC0 ratio was about 74% and the COD was
      diminished to 46% of the initial value. The BOD5/COD ratio increased from 0.01 to
      0.14. To obtain detailed information on the reaction processes during ozonation
      and the resulting oxidation products organic and inorganic anions were analyzed.
      Oxidation and cleavage of the azo group yielded nitrate. Cleavage of the sulfonic
      acid groups of aromatic rings caused an increase in the amount of sulfate. Formic
      acid and oxalic acid were identified as main oxidation products by high
      performance ion chromatography (HPIC). The concentrations of these major products
      were monitored at defined time intervals during ozonation.

PMID- 12046668
TI  - Removal of cyanide from dilute solution using a cell with three-phase three
      dimensional electrode.
AB  - The removal of cyanide from dilute solutions containing free cyanide or
      cuprocyanide was experimentally investigated using a new electrochemical reactor,
      three-phase three-dimensional electrode cell. The experimental results were
      assessed in term of removal efficiency of cyanide. The results showed that the
      reactor could efficiently remove cyanide from the two solutions. The removal
      efficiency reached as high as about 93% for the two solutions by electrolysis for
      10 min at 20 V cell voltage and 0.16 m3/h airflow. It was also observed that the
      removal efficiency depended on the applied cell voltage, airflow, interelectrode
      and initial pH value of the containing-cyanide solution. The former two factors
      have a positive effect while the latter two have a negative effect on cyanide
      removal in the experimental range.

PMID- 12046669
TI  - Application of anaerobic digested residues on safe food production.
AB  - Experiments were conducted in pot culture and field plots to study the effects of
      Anaerobic Digested Residues (ADR) on nitrate accumulation in leaf vegetables,
      which is critical for the safety of food. The results showed that compared to
      chemical fertilizer, ADR could decrease the nitrate accumulation in rape and
      spinach. Furthermore, nitrate content in plant tissue was increased with the
      increase of percentage of chemical nitrogen in the mixture of chemical fertilizer
      and ADR. A comparison of spraying digested slurry with irrigation showed that
      spraying method could reduce the nitrate content of rape, however, a reverse
      result was found in spinach. The nitrate accumulation in rape affected by ADR was
      more apparent in high fertility soil than that in low fertility one. To regulate
      the nitrate accumulation in plant, it was more apparent in rape under greenhouse
      cultivation, while more apparent in spinach under open-air cultivation. The
      results demonstrated that the ADR was effective in the safe food production and
      it may convert the technology to be more profitable.

PMID- 12046670
TI  - Reducing environmental emissions in tanneries.
AB  - Tanning, in particular chrome leather production, is still characterised by an
      inefficient use of raw material and the production of highly polluted wastewater
      and solid wastes. A part of the emissions can be prevented by introducing clean
      tanning technologies, the remaining emissions can be treated. Clean production
      technologies and waste (water) treatment technologies should have a designed
      complimentarity. Anaerobic wastewater treatment with recovery of sulfides, sulfur
      and energy (biogas) is a cornerstone in such integral clean chrome leather
      technology.

PMID- 12046671
TI  - Long-term effects of municipal sewage on soils and pastures.
AB  - Land application of municipal wastewater is widely practised worldwide as a means
      of treating wastes and obtaining a benefit from the water and nutrients by
      growing pastures, trees, and sometimes edible crops such as vegetables, fruit and
      fibre, etc. Irrigation of pastures by treated and untreated sewage near
      Melbourne, Australia, for more than a century has increased heavy metals
      concentrations in the soil, but appears not to have increased their
      concentrations in the herbage and in animal tissues of animals grazed on these
      pastures. There seem to be sound reasons why this practice may be sustainable.

PMID- 12046672
TI  - Environmental monitoring and decision-making.
AB  - This paper combines insights from public administration and statistics to discuss
      the place of water quality monitoring in the decision making process. It uses
      measured data obtained from the monitoring of the River Elbe in the Federal
      Republic of Germany to illustrate the statistical argument. It is further based
      on my experience as a board member of a Water Authority and as a governor of the
      Municipality of Delft. The literature is overviewed by a quick scan on the
      Internet and by using insights obtained from the Global Environmental Monitoring
      Network, GEMS.

PMID- 12046673
TI  - Psychiatric disorders among victims of a courthouse shooting spree: a three-year
      follow-up study.
AB  - This study examined the longitudinal course of psychiatric sequelae of a mass
      shooting incident at a courthouse. A sample of 80 individuals was examined 6-8
      weeks after the incident and 77 of these were reassessed one and three years
      later using the Diagnostic Interview Schedule/Disaster Supplement. Only 5% of the
      study sample met criteria for PTSD after this incident. Universal distress,
      however, was evident as 96% of the respondents reported PTSD symptoms and 75%
      described the incident as "very upsetting." The need for intervention among
      symptomatic individuals not meeting diagnostic criteria should not be discounted
      as subdiagnostic distress may warrant specific intervention.

PMID- 12046675
TI  - Therapist and case manager perceptions of client barriers to treatment
      participation and use of engagement strategies.
AB  - This study of 33 mental health therapists and 30 case managers examined the
      relationship between practitioners' assessments of the importance of potential
      treatment barriers and their use of engagement strategies to overcome those
      barriers and improve treatment participation. Results confirmed the hypothesis
      that workers who viewed treatment barriers as more important were significantly
      more active in their reported efforts to engage clients (r = .28, p < .05).
      Although no significant differences between the two groups were found in overall
      use of engagement strategies, we found a significant interaction effect between
      position and types of strategies used, with therapists employing more discussion
      strategies while case managers were more likely to employ practical engagement
      strategies (F = 35.79, p < .001). Findings suggest the desirability of enhancing
      mental health workers' sensitivity to the range of barriers that clients may
      experience, and expanding the repertoire of engagement strategies they use to
      encourage client retention.

PMID- 12046674
TI  - Employment histories of homeless persons with mental illness.
AB  - This study examined the work histories of 7,228 homeless persons with mental
      illness who were enrolled into the multi-site Access to Community Care and
      Effective Services and Supports (ACCESS) research demonstration program. Multiple
      logistic regression analyses suggest that use of vocational services is
      significantly associated with increased likelihood of paid employment. The role
      of vocational rehabilitation services in removing persons from homelessness and
      improving their quality of life is discussed.

PMID- 12046676
TI  - Cognitive, affective, and physiological expressions of anxiety symptomatology
      among Mexican migrant farmworkers: predictors and generational differences.
AB  - Scant research has examined the mental health of migrant farmworkers in the
      United States. The purposes of the present study were threefold: to assess the
      prevalence levels of anxiety symptoms in a sample of Mexican migrant farmworkers
      in the Midwest United States; to examine the relationship between acculturative
      stress and anxiety; and to determine the variables that significantly predict
      anxiety. High levels were found for overall anxiety and in the cognitive,
      affective, and physiological expressions of anxiety. Elevated acculturative
      stress, low self esteem, ineffective social support, lack of control and choice
      in the decision to live a migrant farmworker lifestyle, low religiosity, and high
      education were significantly related to high anxiety levels. The overall findings
      suggest that Mexican migrant farmworkers who experience high acculturative stress
      may be at risk for developing anxiety-related disorders. The findings highlight
      the necessity of establishing prevention and treatment services for migrant
      farmworkers that increase levels of emotional support, self esteem, and coping
      skills.

PMID- 12046677
TI  - Autonomy versus coercion: reconciling competing perspectives in community mental
      health.
AB  - Clinicians working in community mental health must currently attempt to reconcile
      competing practice perspectives: on the one hand consumer-driven approaches, and
      on the other hand a move to more paternalistic practices, advocated by family
      support groups, and reflected in assertive treatment programs and legislative
      initiatives such as community treatment orders. This article reviews these
      different perspectives, and offers some comments on practice guidelines for those
      working in this clinically and politically complex environment.

PMID- 12046679
TI  - The new "lower is better" lipid goals: are they achievable with today's drugs?
AB  - Both the newly revised Adult Treatment Panel (ATP III) guidelines developed by
      the National Cholesterol Education Program and prospective trials indicate that
      lowering serum low-density lipoprotein cholesterol (LDL-C) to levels of less than
      100 mg/dL is beneficial to minimize the risk of coronary heart disease (CHD).
      However, the risk of acute coronary events is related not just to lipid levels,
      but also to inflammatory pathophysiologic processes that heighten the risk of
      plaque rupture. Statin therapy effectively lowers LDL-C to target (optimal)
      levels, and the newer formulas are proving to provide greater reductions. In
      addition, research demonstrates that statins also counteract thrombosis, reduce
      inflammation, improve endothelial function, block plaque formation and
      progression, and stimulate the growth of new blood vessels in ischemic tissues.
      Global risk reduction-including diet, exercise, weight loss, and drug therapy are
      keys to minimizing CHD events.

PMID- 12046678
TI  - A family intervention program for dual disorders.
AB  - OBJECTIVE: To provide a rationale for working with families of clients with
      psychiatric and substance use disorder, and to describe a new program, family
      intervention for dual disorders (FIDD). METHOD: We developed and manualized the
      FIDD program, which includes both single-family and multiple-family group
      formats. We trained several clinicians at a local mental health center in the
      model and conducted a small pilot study. RESULTS: Clinicians were able to
      implement the program, and to successfully engage families in treatment. Most
      clients demonstrated significant improvements in substance abuse over one to two
      years of treatment. CONCLUSIONS: The FIDD program is feasible and appears to
      promote collaboration between families and professionals, thereby improving the
      course of dual disorders. Controlled research is underway to evaluate the effects
      of the FIDD program on client and family outcomes.

PMID- 12046680
TI  - Practical application of Adult Treatment Panel III guidelines: three illustrative
      case histories.
AB  - The Adult Treatment Panel III (ATP III) guidelines continue to emphasize
      intensive treatment for persons at risk for coronary heart disease (CHD). The
      newest feature is a focus on primary prevention in persons with multiple risk
      factors; the updated guidelines recognize diabetes as a CHD risk equivalent.
      These groups of people already are at high risk and can benefit from increased
      intensive treatment to lower serum low-density lipoprotein cholesterol (LDL-C)
      levels. The ATP III guidelines establish lower targets for LDL-C and triglyceride
      levels and higher targets for the high-density lipoprotein cholesterol level. The
      guidelines also combine several risk factors to estimate the probability of CHD
      with use of the Framingham risk point-scoring formula and emphasize the
      multifactorial benefits of drug therapy as an adjunct to lifestyle changes.

PMID- 12046681
TI  - Adult Treatment Panel III: do we really need another set of cholesterol
      guidelines?
AB  - Reducing high levels of plasma low-density lipoprotein cholesterol (LDL-C) is
      still the primary focus of the Adult Treatment Panel III (ATP III) guidelines
      developed by the National Cholesterol Education Program. The LDL-C goal of less
      than 100 mg/dL for those with coronary heart disease (CHD) is now extended to
      patients with diabetes and those with a Framingham risk score of greater than 20%
      in 10 years, both of which are now considered "CHD risk equivalents."
      Consequently, many more people will be considered candidates for aggressive lipid
      lowering therapy under the new ATP III guidelines. Other prominent features in
      the new guidelines include determining an individual's absolute risk category by
      using a nine-step process, instituting therapeutic lifestyle changes to reduce
      LDL-C levels, and strategies for treating patients with other forms of
      dyslipidemia such as metabolic syndrome.

PMID- 12046682
TI  - Thalidomide in multiple myeloma.
AB  - Thalidomide--removed from widespread clinical use by 1962 because of severe
      teratogenicity--has anti-angiogenic and immunomodulatory effects, including the
      inhibition of TNF alpha. It has returned to practice as an effective oral agent
      in the management of various disease states including erythema nodosum leprosum,
      for which it was FDA-approved in 1998, and more recently certain malignancies,
      including multiple myeloma. Whilst the mechanism of action of thalidomide remains
      incompletely understood, considerable insight has been generated by extensive
      preclinical studies in multiple myeloma. Moreover, clinical trials both as a
      single agent and in combination have confirmed benefit in relapsed and refractory
      disease. Thalidomide's role in treating newly diagnosed patients is currently
      under study and it is now established as an important therapeutic option in the
      treatment of multiple myeloma.

PMID- 12046683
TI  - Recent advances in multiple myeloma immunotherapy.
AB  - Multiple myeloma (MM) responds to, but is not cured by, chemotherapy and may
      therefore be amenable to tumor-specific immunization in the setting of minimal
      residual disease. The idiotype of the monoclonal immunoglobulin expressed by the
      tumor provides a clear tumor-specific antigen. Patients with follicular lymphoma
      have unequivocally established that idiotypic vaccination, administered when
      patients have minimal residual disease, has an antitumor effect and potential to
      improve the clinical outcome. This result and preclinical studies demonstrating
      that MM cells display idiotypic peptides on their surface in a form suitable for
      recognition and killing by host T cells, foster the application of idiotypic
      vaccination in MM. The current vaccine production involves idiotype protein
      purification for each patient followed by conjugation to exogenous, immunogenic
      carriers in order to break immunological tolerance. Furthermore, recent advances
      in molecular cloning and development of novel antigen delivery systems are making
      it possible to streamline the production of equally or more effective idiotypic
      vaccines. Particularly, DNA vaccines utilising genetic carriers to target
      idiotype on dendritic cells in vivo have proven successful in preclinical models.
      Additional candidate T cell antigens, such as MUC1, the cancer-testis antigens,
      and telomerase have been identified as potential targets for immunization. The
      possibility of using whole myeloma cells as a source of tumor antigens for
      immunotherapy is also being actively explored. Finally, clinical studies have
      begun in which dendritic cells are generated ex vivo, loaded with tumor
      antigen(s), and reinfused to immunize patients.

PMID- 12046684
TI  - Allogeneic hematopoietic cell transplantation for multiple myeloma.
AB  - At the present time, allogeneic hematopoetic stem cell transplantation (AHSCT) is
      the only proven treatment for multiple myeloma (MM) that is potentially curative.
      This conclusion is based on observations of patients who have undergone AHSCT and
      are living disease-free for 5-15 years. While patients who receive either
      allogeneic or autologous stem cell transplants for MM have similar 3-5 year
      survival, only allograft recipients appear to enjoy long-term disease free
      survival. This is most likely due to an allogeneic graft-versus-myeloma effect,
      demonstrated most dramatically by complete responses observed after the simple
      infusion of donor lymphocytes for patients who have relapsed after a prior
      allograft. The very high transplant related mortality associated with standard
      allogeneic stem cell transplantation is currently the major limitation to wider
      use of this potentially curative treatment modality. Complications are age
      related and thus standard AHSCT is offered only to patients under age 55; further
      limiting the utility of this treatment. The challenge for clinical investigators
      will be to reduce the incidence of post-transplant complications for patients
      receiving AHSCT for MM. These strategies include the use of non-ablative
      conditioning regimens, the use of peripheral blood stem cells rather than bone
      marrow, graft engineering and targeted conditioning therapies such as bone
      seeking radioisotopes. In one such approach, tandem autologous/non-ablative
      allogeneic transplants have been shown to result in relatively low mortality,
      high complete response rates and 1-year survivals of 81%. Further follow-up and
      randomized trials will help to define the utility of this strategy.

PMID- 12046685
TI  - Urinary proteins and renal dysfunction in patients with multiple myeloma.
AB  - Besides bone pain, pathologic fractures, anaemia, and recurrent infectious
      diseases, renal failure is one of the most serious complications in multiple
      myeloma patients. Its incidence is generally underestimated because of the low
      reliability of the parameters routinely used for the evaluation of renal
      dysfunction. Other laboratory tests in the literature are reported to be more
      suitable to better define the extension of the renal impairment, namely urinary
      proteins or creatinine clearance. We here report on the clinical implication of
      urinary parameters in defining the renal function in myeloma patients.

PMID- 12046686
TI  - Bcl-2, Bcl-xL and c-FLIP(L) potentially regulate the susceptibility of human
      peripheral blood monocyte-derived dendritic cells to cell death at different
      developmental stages.
AB  - We examined the susceptibility of human monocyte-derived dendritic cells (DCs) to
      spontaneous and CD95-mediated cell death at different developmental stages. Time
      course experiments revealed that the susceptibility of mature dendritic cells
      (mDCs) to spontaneous cell death was significantly lower than that of immature
      dendritic cells (iDCs) in a long-term culture under cytokine-free conditions, and
      the treatment with GM-CSF rescued these cells from spontaneous cell death at the
      late culture period. iDCs and mDCs expressed similar levels of CD95 whereas both
      cell types were relatively resistant to CD95-mediated cell death. Antigen (Ag)
      specific and nonspecific cognate interaction with T cells failed to cause cell
      death of iDCs and mDCs. iDCs constitutively expressed transcripts and
      intracellular products of Bcl-2 and Bcl-xL, but not cellular FLICE-inhibitory
      protein(long (c-FLIP(L)), while the increased expressions of Bcl-2, Bcl-xL and c
      FLIP(L) were observed in mDCs. These results suggest that the selective
      expressions of Bcl-2, Bcl-xL and c-FLIP(L) may be involved in the difference in
      the susceptibility to cell death between iDCs and mDCs.

PMID- 12046687
TI  - Measurements of IL-6, soluble IL-6 receptor and soluble gp130 in sera of B-cell
      lymphoma patients. Does viscum album treatment affect these parameters?
AB  - Interleukin-6 (IL-6) can be involved in several diseases including lymphoid
      malignancies. This cytokine binds to soluble IL-6 receptor (sIL-6R) circulating
      in blood, leading to signal transduction via gp130. Soluble IL-6R shows agonistic
      activity for IL-6, and the soluble form of gp130 (sgp130) an antagonistic effect
      against the complex IL-6/sIL-6R. Viscum album extract (Iscador) as an
      immunomodulator is used in the treatment of malignant disorders. In this study we
      investigated the effect of this treatment on the serum levels of IL-6, sIL-6R and
      sgp130 in B-cell lymphoma patients (n = 27), in comparison to healthy controls (n
      = 28). Twenty-one of 27 patients had been treated previously with
      chemo/radiotherapy. The patients were divided into two groups; those with short
      term (investigated before and during treatment) or those with long-term Viscum
      album (VA) therapy (investigated during therapy). The serum levels of the three
      parameters were determined by ELISA. In patients having short-term treatment IL-6
      values were similar to those of controls. During long-term therapy the values
      were significantly lower (P<0.05). The values of sIL-6R were elevated only in
      long-term treated patients (P<0.05), the values of sgp130 in both short-term
      (P<0.05) and in long-term treated patients (P=0.001). There is a significant
      correlation (P<0.05) between levels of sIL-6R and sgp130 in both therapy groups
      at 24 hours after injection. This indicates that the potent effect of sIL-6R on
      the biological activity of IL-6 could be inhibited by sgp130 as antagonist.
      Clinical data show that half of the patients (6/12) with long-term treatment had
      a continuous complete remission, whereas only 2/15 patients with short-term
      treatment had a complete remission.

PMID- 12046688
TI  - Interaction between phagocytosis and IL-1beta production by rat peritoneal
      macrophages.
AB  - The capacity of rat peritoneal macrophages to produce interleukin-1beta (IL
      1beta) following phagocytosis of latex particles in vivo and in vitro was
      examined. In both cases, a marked increase in IL-1beta secretion was observed,
      although the level of the cytokine secreted in vivo was higher than that observed
      after incubation of the cells with latex beads in vitro. It is presumed that this
      difference is due to stimulation of the peritoneal macrophages by endogenous
      produced factors/cytokines prior and during phagocytosis in vivo. Macrophages
      stimulated with LPS showed a level of IL-1beta almost identical to that obtained
      after incubation with latex. Following phagocytosis in vivo and further
      stimulation with LPS in vitro, the cells showed an additional increase in IL
      1beta production, whereas this additive effect could not be observed when
      incubation with both latex and LPS was carried out in vitro. The results suggest
      different patterns for IL-1beta production by rat peritoneal macrophages,
      depending on the way they are stimulated for phagocytosis.

PMID- 12046689
TI  - Okadaic acid increases ARNT homodimer transactivation potential.
AB  - The human aryl hydrocarbon nuclear translocator (hARNT) protein belongs to the
      family of basic helix-loop-helix (bHLH) PAS transcription factors and regulates a
      range of cellular processes by either homodimerizing or heterodimerizing with
      other bHLH-PAS proteins. hARNT has been shown to be almost exclusively
      phosphorylated on serine residues. However, regulation of hARNT with respect to
      phosphorylation remains poorly understood. The phosphatase inhibitor okadaic acid
      was used to explore whether a change in hARNT phosphorylation status could
      influence hARNT homodimer activity. The hARNT homodimer has been shown to bind to
      E boxes and E-box binding factors are believed to be important in the regulation
      of cell differentiation and proliferation. Okadaic acid significantly increased
      hARNT-mediated class B, E-box-driven reporter activity in COS-1 cells,
      transiently expressing hARNT without affecting hARNT protein levels. This
      alteration in hARNT-mediated class B, E-box-driven reporter activity correlates
      with an observed increase in [32P]orthophosphate incorporation into hARNT.
      Treatment with okadaic acid resulted in a 12-fold increase in [32P]orthophosphate
      incorporation into hARNT that was transiently expressed in COS-1 cells; an
      increase in the number of tryptic phosphopeptides generated from hARNT digests on
      two-dimensional phosphopeptide maps was also observed. Despite the significant
      increase in [32P]orthophosphate incorporation into hARNT, serine remained the
      predominantly phosphorylated residue. Clearly, increased serine phosphorylation
      does not appear to negatively regulate hARNT homodimerization or transactivation
      potential. These results demonstrate that increased hARNT homodimer signaling in
      COS-1 cells may result from a direct change in hARNT phosphorylation status.

PMID- 12046690
TI  - Degradation of IkappaBalpha in activated RAW264.7 cells is blocked by the
      phosphatidylinositol 3-kinase inhibitor LY294002.
AB  - The mechanism by which lipopolysaccharide (LPS) or phorbol 12-myristate 13
      acetate (PMA) induces production of proinflammatory cytokines in murine
      macrophages, and the role of phosphatidylinositol 3-kinase (PI3-kinase) have not
      been well investigated. Activation of nuclear factor kappaB (NF-kappaB) is
      initiated by the phosphorylation of the inhibitory subunit, IkappaB, which
      targets IkappaB for degradation and leads to the release of active NF-kappaB. In
      this study we demonstrate that 2-(4-morpholinyl)-8-phenylchromone (LY294002),
      which inhibits PI3-kinase, specifically inhibited degradation of IkappaBalpha in
      RAW264.7 cells stimulated with interferon-gamma (IFN-gamma) plus LPS or IFN-gamma
      plus PMA. To elucidate the importance of this activity in RAW264.7 cells, we
      examined tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6
      production in the activated cells. Pretreatment of the cells with LY294002
      resulted in the inhibition of TNF-alpha and IL-6 production in RAW264.7 cells
      stimulated with IFN-gamma plus LPS or IFN-gamma plus PMA. Furthermore, LY294002
      inhibited the production of nitric oxide (NO) in RAW264.7 cells stimulated with
      IFN-gamma plus LPS or IFN-gamma plus PMA. LY294002 also inhibited inducible NO
      synthase (iNOS) mRNA expression in the activated RAW264.7 cells. In conclusion,
      the present results suggest that PI3-kinase is involved in the signal
      transduction pathway responsible for LPS- or PMA-mediated TNF-alpha and IL-6
      production, and that LY294002 inhibits NO generation through blocking the
      degradation of IkappaBalpha in activated RAW264.7 cells.

PMID- 12046691
TI  - A comparative study of cytotoxic effects of N-ethyl-N-nitrosourea, adriamycin,
      and mono-(2-ethylhexyl)phthalate on mouse primordial germ cells.
AB  - Several strategies for the assessment of reproductive toxicity of chemical
      compounds has have been proposed. In the present work, we devised experimental in
      vitro assays to test the effect of potential toxicants on proliferating
      primordial germ cells (PGCs) in vitro using recently developed methods for
      isolation and culture of mouse PGCs. Primordial germ cells are the embryonic
      precursors of gametes of the adult that carry the genome from generation to
      generation. Any damage or mutations caused to these cells by potential toxicants
      might impair normal reproduction and be transmitted to next generation. Three
      representative compounds, N-ethyl-N-nitrosourea (ENU), adriamycin (ADR), and mono
      (2-ethylhexyl)phthalate (MEHP), toxic to different targets and known to affect
      germ cell development and impair fertility, were tested on PGCs in culture using
      three different experimental protocols. Survival and growth of PGCs and their
      ability to adhere to cell monolayers, were taken as endpoints for drug effects.
      For each compound, sublethal and acute toxicity doses were determined. In
      addition, information about the mechanisms of action of these compounds on PGCs
      was obtained. Whereas the effects of ENU and ADR on PGCs were attributable to
      growth inhibition and apoptosis induction, MEHP affected PGC adhesion to somatic
      cells without significantly altering their growth and survival. The results of
      our in vitro tests were not always exactly predictive of the effects of the
      tested compounds on PGCs in vivo, determined in parallel experiments in which
      pregnant mice were exposed to the same compounds. Nevertheless, they can provide
      information on the sensitivity of PGCs to the direct action of drugs or the
      mechanisms of action of such agents.

PMID- 12046692
TI  - Morphological and biochemical integrity of human liver slices in long-term
      culture: effects of oxygen tension.
AB  - We tested the effects of low (20% O2) and high (70% O2) oxygen tension on the
      morphological and biochemical integrity of human liver slices incubated for up to
      72 h in supplemented Williams' E medium in a dynamic rotating culture system.
      High oxygen tension was more effective than low oxygen tension for preserving
      morphological integrity in long-term culture (48-72 h). After 72 h of culture
      with 70% O2, the lobular pattern was well preserved, and the survival of
      hepatocytes (approximately 80%) and other cell types was good.
      Immunohistochemical studies showed good preservation of the region-specific
      expression of CYP2EI and CYP3A4 isoenzymes for up to 72 h of incubation in 70%
      O2. As compared to 20% O2, the oxidized glutathione content and reactive oxygen
      species production were slightly increased in 70% O2, suggesting that minimal
      oxidative stress occurred with the high oxygen tension. In conclusion, despite
      slight oxidative stress associated with high oxygen tension, 70% O2 appeared more
      appropriate than 20% O2 for preserving the morphological and biochemical
      integrity of human liver slices cultured in a dynamic organ culture system for up
      to 72 h.

PMID- 12046693
TI  - Enhanced expression of a novel protein in human cancer cells: a potential aid to
      cancer diagnosis.
AB  - Cap43 is a protein whose RNA is induced under conditions of severe hypoxia or
      prolonged elevations of intracellular calcium. Cap43 protein is expressed at low
      levels in normal tissues; however, in a variety of cancers, including lung,
      brain, melanoma, liver, prostate, breast, and renal cancers, Cap43 protein is
      overexpressed in cancer cells. The low level of expression of Cap43 in some
      normal tissues compared to their cancerous counterparts combined with the high
      stability of Cap43 protein and mRNA makes the Cap43 gene a new, important cancer
      marker. We hypothesize that the mechanism of Cap43 overexpression in cancer cells
      involves a state of hypoxia characteristic of cancer cells where the Cap43
      protein becomes a signature for this hypoxic state.

PMID- 12046694
TI  - In vitro cytotoxicity testing with fluorescence-based assays in cultured human
      lung and dermal cells.
AB  - An in vitro study using human cultured cells was conducted to determine the
      reliability of fluorescence-based cell viability indicators with traditional in
      vitro cytotoxicity testing methods. Human lung epithelial carcinoma (A549) cells,
      and human embryonic skin (WS1) and lung (HFLI) fibroblasts were studied in
      culture to evaluate their potential to screen for cytotoxicity and to compare to
      previous protocols conducted in our laboratory. Confluent monolayers were
      incubated in the absence or presence of increasing concentrations of test
      chemicals for 24 h, and fluorescent-labeled probes were used to assess toxicity.
      Eight chemicals, including mercuric chloride, copper sulfate, sodium fluoride,
      thioridazine HCl, paraquat, amitriptyline-HCl, verapamil-HCl and chloroquine
      sulfate, were tested with each cell line using calcein-AM and Sytox. The data
      suggest that fluorescent probes are sensitive indicators of cytotoxicity and
      contribute to understanding the mechanisms for each chemical. In combination with
      previously published reports, the similarity of results among cell lines may be
      explained by the origin of the cell lines rather than by the diversity of the
      methods and indicators employed.

PMID- 12046695
TI  - Use of the ventricular propagated excitation model in the magnetocardiographic
      inverse problem for reconstruction of electrophysiological properties.
AB  - A novel magnetocardiographic inverse method for reconstructing the action
      potential amplitude (APA) and the activation time (AT) on the ventricular
      myocardium is proposed. This method is based on the propagated excitation model,
      in which the excitation is propagated through the ventricle with nonuniform
      height of action potential. Assumption of stepwise waveform on the transmembrane
      potential was introduced in the model. Spatial gradient of transmembrane
      potential, which is defined by APA and AT distributed in the ventricular wall, is
      used for the computation of a current source distribution. Based on this source
      model, the distributions of APA and AT are inversely reconstructed from the QRS
      interval of magnetocardiogram (MCG) utilizing a maximum a posteriori approach.
      The proposed reconstruction method was tested through computer simulations.
      Stability of the methods with respect to measurement noise was demonstrated. When
      reference APA was provided as a uniform distribution, root-mean-square errors of
      estimated APA were below 10 mV for MCG signal-to-noise ratios greater than, or
      equal to, 20 dB. Low-amplitude regions located at several sites in reference APA
      distributions were correctly reproduced in reconstructed APA distributions. The
      goal of our study is to develop a method for detecting myocardial ischemia
      through the depression of reconstructed APA distributions.

PMID- 12046696
TI  - FEM analysis of predicting electrode-myocardium contact from RF cardiac catheter
      ablation system impedance.
AB  - We used the finite-element method (FEM) to model and analyze the resistance
      between the catheter tip electrode and the dispersive electrode during radio
      frequency cardiac catheter ablation for the prediction of myocardium-electrode
      contact. We included deformation of the myocardial surface to achieve accurate
      modeling. For perpendicular catheter contact, we measured the side view of
      myocardial deformation using X-ray projection imaging. We averaged the
      deformation contour from nine samples, and then incorporated the contour
      information into our FEM model. We measured the resistivity of the bovine
      myocardium using the four-electrode method, and then calculated the resistance
      change as the catheter penetrated into the myocardium. The FEM result of
      resistance versus catheter penetration depth matches well with our experimental
      data.

PMID- 12046697
TI  - Effects of stochastic sodium channels on extracellular excitation of myelinated
      nerve fibers.
AB  - The effects of the stochastic gating properties of sodium channels on the
      extracellular excitation properties of mammalian nerve fibers was determined by
      computer simulation. To reduce computation time, a hybrid multicompartment cable
      model including five central nodes of Ranvier containing stochastic sodium
      channels and 16 flanking nodes containing detenninistic membrane dynamics was
      developed. The excitation properties of the hybrid cable model were comparable
      with those of a full stochastic cable model including 21 nodes of Ranvier
      containing stochastic sodium channels, indicating the validity of the hybrid
      cable model. The hybrid cable model was used to investigate whether or not the
      excitation properties of extracellularly activated fibers were influenced by the
      stochastic gating of sodium channels, including spike latencies, strength
      duration (SD), current-distance (IX), and recruitment properties. The stochastic
      properties of the sodium channels in the hybrid cable model had the greatest
      impact when considering the temporal dynamics of nerve fibers, i.e., a large
      variability in latencies, while they did not influence the SD, IX, or recruitment
      properties as compared with those of the conventional deterministic cable model.
      These findings suggest that inclusion of stochastic nodes is not important for
      model-based design of stimulus waveforms for activation of motor nerve fibers.
      However, in cases where temporal fine structure is important, for example in
      sensory neural prostheses in the auditory and visual systems, the stochastic
      properties of the sodium channels may play a key role in the design of stimulus
      waveforms.

PMID- 12046699
TI  - A nonlinear adaptive method of elimination of power line interference in ECG
      signals.
AB  - A new method of elimination of power line noise in electrocardiogram signals is
      presented. The proposed method employs, as its main building block, a recently
      developed signal processing algorithm capable of extracting a specified component
      of a signal and tracking its variations over time. Design considerations and
      performance of the proposed method are presented with the aid of computer
      simulations. Superior performance is observed in terms of effective elimination
      of noise under conditions of varying powerline interference frequency. The
      proposed method presents a simple and robust structure which complies with
      practical constraints involved in the problem such as low computational resource
      availability and low sampling frequency.

PMID- 12046698
TI  - Spatiotemporal EEG/MEG source analysis based on a parametric noise covariance
      model.
AB  - A method is described to incorporate the spatiotemporal noise covariance matrix
      into a spatiotemporal source analysis. The essential feature is that the
      estimation problem is split into two parts. First, a model is fitted to the
      observed noise covariance matrix. This model is a Kronecker product of a spatial
      and a temporal matrix. The spatial matrix models the spatial covariances by a
      function dependent on sensor distance. The temporal matrix models the temporal
      covariances as lag dependent. In the second part, sources are estimated given
      this noise model, which can be done very efficiently due to the Kronecker
      formulation. An application to real electroencephalogram (EEG) data shows that
      the noise model fits the data very well. Simulation results show that the
      resulting source estimates are more precise than those obtained from a standard
      analysis neglecting the noise covariance. In addition, the estimated standard
      errors of the source parameter estimates are far more precise than those obtained
      from a standard analysis. Finally, the source parameter standard errors are used
      to investigate the effects of temporal sampling. It is shown that increasing the
      sampling by a factor x, decreases the standard errors of all source parameters
      with the square root of x.

PMID- 12046700
TI  - Evidence of state-dependent interhemispheric relationships in lizard EEG during
      the awake state.
AB  - The electroencephalogram (EEG) from both hemispheres of eight Canary lizards
      Gallotia galloti was registered at 25 degrees C and 35 degrees C during awake
      state with open eyes (OE) and closed eyes. The possible interdependence between
      the recorded EEGs was assessed by means of newly developed methods of
      multivariate nonlinear time-series analysis. The interdependence turned out to be
      significant and greater for the OE state at both temperatures, although it was of
      linear type in most of the cases. We conclude that the methods can be
      successfully applied to study the interdependence between noisy, low-amplitude
      EEGs.

PMID- 12046701
TI  - Nonlinear nonstationary Wiener model of infant EEG seizures.
AB  - This paper presents the estimation of a nonstationary nonlinear model of seizures
      in infants based on parallel Wiener structures. The model comprises two parts and
      is partly derived from the Roessgen et al. seizure model. The first part consists
      of a nonlinear Wiener model of the pure background activity, and the second part
      in a nonlinear Wiener model of the pure seizure activity with a time-varying
      deterministic input signal. The two parts are then combined in a parallel
      structure. The Wiener model consists of an autoregressive moving average filter
      followed by a nonlinear shaping function to take into account the non-Gaussian
      statistical behavior of the data. Model estimation was performed on 64 infants of
      whom four showed signs of clinical and electrical seizures. Model validation is
      performed using time-frequency-based entropy distance and shows an averaged
      improvement of 50% in modeling performance compared with the Roessgen model.

PMID- 12046702
TI  - Movement quantification in epileptic seizures: a new approach to video-EEG
      analysis.
AB  - It is common that epileptic seizures induce uncoordinated movement in a patient's
      body. This movement is a relevant clinical factor in seizure identification.
      Nevertheless, quantification of this information has not been an object of much
      attention from the scientific community. In this paper, we present our effort in
      developing a new approach to the quantification of movement patterns in patients
      during epileptic seizures. We attach markers at landmark points of a patient's
      body and use a camera and a commercial video-electroencephalogram (EEG) system to
      synchronously register EEG and video during seizures. Then, we apply image
      processing techniques to analyze the video frames and extract the trajectories of
      those points that represent the course of the quantified movement of different
      body parts. This information may help clinicians in seizure classification. We
      describe the framework of our system and a method of analyzing video in order to
      achieve the proposed goal. Our experimental results show that our method can
      reflect quantified motion patterns of epileptic seizures, which cannot be
      accessed by means of traditional visual inspection of video recordings. We were
      able, for the first time, to quantify the movement of different parts of a
      convulsive human body in the course of an epileptic seizure. This result
      represents an enhanced value to clinicians in studying seizures for reaching a
      diagnosis.

PMID- 12046703
TI  - Magnetic resonance diffractive imaging.
AB  - Magnetic resonance (MR) diffractive imaging is proposed as a new approach to MR
      angiography. The expression of the nuclear MR signal is similar to the equation
      for the Fresnel diffraction of a three-dimensional (3-D) object in light or sound
      waves. The proposed technique offers the possibility of fast angiographic imaging
      and the on-line reconstruction of 3-D volumetric images using the holographic
      technique. Static imaging experiments using an ultra-low-field MRI system are
      performed to verify the feasibility of the technique. It is shown that the images
      focused on an arbitrary plane can be reconstructed from data scanned in two
      dimensions, even though blurred image data is superimposed on the image.
      Moreover, the 3-D image can be observed in a coherent optical imaging system.
      This study demonstrates the possibility of the proposed method as a fast imaging
      technique for MR angiography.

PMID- 12046704
TI  - Miniature acoustic guidance system for endotracheal tubes.
AB  - Ensuring that the distal end of an endotracheal tube (ETT) is properly located
      within the trachea, and that the tube is not obstructed by mucus deposition, is a
      major clinical concern in patients that require mechanical ventilation. A novel
      acoustic system was developed to allow for the continuous monitoring of ETT
      position and patency. A miniature sound source and two sensing microphones are
      placed in-line between the ventilator hose and the proximal end of the ETT.
      Reflections of an acoustic pulse emitted into the ETT lumen and the airways are
      digitally analyzed to estimate the location and degree of lumen obstruction, as
      well as the position of the distal end of the tube in the airway. The system was
      evaluated through in vitro studies and in a rabbit model. The system
      noninvasively estimated tube position in vivo to within roughly 4.5 mm, and
      differentiated between proper tracheal, and erroneous bronchial or esophageal
      intubation in all cases. In addition, the system estimated the area and location
      of lumen obstructions in vitro to within 14% and 3.5 mm, respectively. These
      findings indicate that this miniature technology could improve the quality of
      care provided to the ventilated adult and infant.

PMID- 12046705
TI  - Characterization of micromachined spiked biopotential electrodes.
AB  - We present the characterization of dry spiked biopotential electrodes and test
      their suitability to be used in anesthesia monitoring systems based on the
      measurement of electroencephalographic signals. The spiked electrode consists of
      an array of microneedles penetrating the outer skin layers. We found a
      significant dependency of the electrode-skin-electrode impedance (ESEI) on the
      electrode size (i.e., the number of spikes) and the coating material of the
      spikes. Electrodes larger than 3 x 3 mm2 coated with Ag-AgCl have sufficiently
      low ESEI to be well suited for electroencephalograph (EEG) recordings. The
      maximum measured ESEI was 4.24 k(omega) and 87 k(omega), at 1 kHz and 0.6 Hz,
      respectively. The minimum ESEI was 0.65 k(omega) an 16 k(omega), at the same
      frequencies. The ESEI of spiked electrodes is stable over an extended period of
      time. The arithmetic mean of the generated dc offset voltage is 11.8 mV
      immediately after application on the skin and 9.8 mV after 20-30 min. A spectral
      study of the generated potential difference revealed that the ac part was
      unstable at frequencies below approximately 0.8 Hz. Thus, the signal does not
      interfere with a number of clinical applications using real-time EEG. Comparing
      raw EEG recordings of the spiked electrode with commercial Zipprep electrodes
      showed that both signals were similar. Due to the mechanical strength of the
      silicon microneedles and the fact that neither skin preparation nor electrolytic
      gel is required, use of the spiked electrode is convenient. The spiked electrode
      is very comfortable for the patient.

PMID- 12046706
TI  - Dependence of induced transmembrane potential on cell density, arrangement, and
      cell position inside a cell system.
AB  - A nonuniform transmembrane potential (TMP) is induced on a cell membrane exposed
      to external electric field. If the induced TMP is above the threshold value, cell
      membrane becomes permeabilized in a reversible process called
      electropermeabilization. Studying electric potential distribution on the cell
      membrane gives us an insight into the effects of the electric field on cells and
      tissues. Since cells are always surrounded by other cells, we studied how their
      interactions influence the induced TMP. In the first part of our study, we
      studied dependence of potential distribution on cell arrangement and density in
      infinite cell suspensions where cells were organized into simple-cubic, body
      centered cubic, and face-centered cubic lattice. In the second part of the study,
      we examined how induced TMP on a cell membrane is dependent on its position
      inside a three-dimensional cell cluster. Finally, the results for cells inside
      the cluster were compared to those in infinite lattice. We used numerical
      analysis for the study, specifically the finite-element method (FEM). The results
      for infinite cell suspensions show that the induced TMP depends on both: cell
      volume fraction and cell arrangement. We established from the results for finite
      volume cell clusters and layers, that there is no radial dependence of induced
      TMP for cells inside the cluster.

PMID- 12046707
TI  - Analysis and development of locomotion devices for the gastrointestinal tract.
AB  - The authors are developing devices for semi-autonomous or autonomous locomotion
      in the gastrointestinal (GI) tract. In this paper, they illustrate the systematic
      approach to the problem of "effective" locomotion in the GI tract and the
      critical analysis of "inchworm" locomotion devices, based on extensor and clamper
      mechanisms. The fundamentals of locomotion and the practical problems encountered
      during the development and the testing (in vitro and in vivo) of these devices
      are discussed. A mini device capable of propelling itself in the colon and
      suitable to perform, at least, rectum-sigmoidoscopy (the tract where
      approximately 60% of all colon cancers are found) is presented. This paper
      introduces preliminary, but useful, concepts for understanding, modeling and
      improving the performance of virtually any existing and novel devices for
      endoscopy of the GI tract.

PMID- 12046708
TI  - Estimation of K distribution parameters using neural networks.
AB  - The K distribution is an accurate model for ultrasonic backscatter. A neural
      approach is developed to estimate K distribution parameters. Accuracy and
      consistency of the estimates from simulated K and envelope data compare favorably
      with other techniques. Neural networks can potentially be used as a complementary
      technique for tissue characterization.

PMID- 12046709
TI  - A novel ferromagnetic thermo-stent for plaque stabilization that self-regulates
      the temperature.
AB  - The purpose of this study is to investigate the vascular wall with a thermally
      self-regulating, cylindrical stent made of a low Curie temperature ferromagnetic
      alloy. Physiologic saline was circulated in the silicone model vessel implanted
      with the stent. The stent-temperature remained nearly constant for variable
      saline flows, saline temperatures, and magnetic flux densities. Stent implants of
      this type in human blood vessels could potentially enable thermotherapy and
      temperature determination without catheterization.

PMID- 12046710
TI  - Professional self-regulation--another Enron casualty?

PMID- 12046711
TI  - Evaluation of Alabama's mandatory continuing education program for
      reasonableness, access, and value.
AB  - BACKGROUND: As a measure of quality control, the Alabama Board of Nursing
      subjected the regulations for mandatory continuing education (MCE) for licensure
      to an evaluation of their impact and effectiveness. This study focused on
      licensees' perceptions of the regulations regarding reasonableness, access, and
      value. METHOD: Evaluation research methods were used to answer research questions
      related to the rules governing continuing education (CE) requirements for nursing
      licensure. Data were obtained from a survey of a random sample (N = 406) of RNs
      and licensed practical nurses. Both qualitative and quantitative methods were
      applied to data analysis. FINDINGS: Requirements for CE were perceived as
      reasonable; however, concerns were identified related to cost, access, and
      quality of presentations. Licensees perceived CE to be of value, and applied CE
      to decision-making and action in nursing practice. Chi-square analysis was
      significant to license type related to selected variables (e.g., rights and
      responsibilities). Qualitative analysis provided insight regarding licensees'
      concerns and recommendations for change. CONCLUSION: Mandatory continuing
      education (MCE) plays a significant role in promoting competence in nursing
      practice and is a mechanism for enhancing public protection. A high noncompliance
      rate on the MCE audit has ramifications for enforcement regulations.

PMID- 12046712
TI  - A study of professional nurses' perceptions of patient education.
AB  - BACKGROUND: The purpose of this study was to describe the professional nurses'
      perception of the role of patient educator and to determine factors inhibiting
      and enhancing patient teaching. METHOD: One hundred and twenty-four hospital
      based, acute-care professional nurses were randomly selected from a State Board
      of Nursing list and surveyed by mail. RESULTS: Ninety-two percent of nurses
      reported that patient education was a priority in their nursing care. The top
      three factors inhibiting patient education were time, staffing, and receptiveness
      of the patient. The top three enhancers were providing more time to teach,
      providing inclusive teaching guidance sheets, and making resources more
      accessible. CONCLUSION: Patient education is a valuable part of professional
      nurses' practice, but many factors impede this nursing function. Key
      recommendations to enhance patient teaching were suggested, including improving
      efficiencies in patient care, supporting the staff nurse educational role, and
      providing essential resources based on survey results.

PMID- 12046713
TI  - Evidence-based education and the evaluation of a critical care course.
AB  - A critical care nursing course was designed to enhance knowledge attainment for
      RNs new to critical care, and to prepare seasoned critical care nurses for
      specialty certification. The convenience sample of nurses (N = 57) was either
      enrolled in the 16-session course (n = 27) or assigned to a control group (n =
      30). A repeated measures design allowed data collection at three time points:
      precourse, course completion, and 6 months after course completion. Mean scores
      on the Basic Knowledge Assessment Tool were significantly higher for course
      participants at the time of course completion, and scores continued to remain
      high 6 months later, demonstrating important retention of critical care
      knowledge.

PMID- 12046714
TI  - How many is too many? Collaboration of multiple nursing organizations for
      professional development.
AB  - Representatives of 11 nursing organizations developed a unique consortium to
      produce an ongoing series of annual conferences focused on promoting professional
      nursing leadership among nurses in diverse practice areas including acute care,
      long-term care, community health, and nursing education. The consortium
      strategically added members and refined the format of the conferences based on
      participant feedback. The conferences feature a keynote speaker and practice
      based breakout sessions designed to facilitate futuristic thinking among nurses.
      The conference is associated with a legislative roundtable to support interaction
      between nurses and legislators. Future expansion of the consortium will include
      representation of advanced practice nurses. The development of the consortium and
      its highly efficient methods of operation are described in this article as an
      example of multi-organizational collaboration to promote professional nursing
      leadership. Bonds have been formed between the consortium member organizations
      that are mutually beneficial to the members of all.

PMID- 12046715
TI  - Incorporating educational theory into critical care orientation.
AB  - This article describes the development and implementation of a critical care
      total education system, which includes an orientation program. The educational
      process in this unit reflects Benner's model of novice to expert integrated with
      Schon's theory of reflective practice and Cranton's transformational learning
      theory. This program reflects an educational philosophy that facilitates learning
      on entry into the new workplace, and an established continuum of expected
      acquisition of knowledge, practice skills, attitudes, and critical thinking
      abilities promoting the transition from novice to expert.

PMID- 12046716
TI  - Precepting in 2002.
AB  - Preceptorships have been used to bridge the gap between nursing education and the
      reality of the workplace. The role of preceptors to prepare new or transitioning
      nurses to function more efficiently and earlier has become increasingly important
      in recent years. To foster positive attitudes in the experienced nurses toward
      accepting and functioning in the roles of preceptors, nursing administration and
      nursing education must collaborate. Preceptors have the ability to shape,
      nurture, influence, and support novice nurses. Experienced nurses hold the
      responsibility to encourage this commitment.

PMID- 12046717
TI  - Association of maternal blood pressure and hemoglobin level with organochlorines
      in human milk.
AB  - Milk samples of women from the general population in Lucknow were analysed by gas
      liquid chromatography to determine the concentration of organochlorine pesticides
      and their possible association with maternal characteristics. p,p'-DDT (dichloro
      diphenyltrichloroethane), p,p-DDE (dichloro diphenyltrichloroethylene), p,p'-DDD
      (dichloro diphenyl dichloroethane), alpha, beta gamma and delta isomers of
      hexachlorocyclohexane (HCH) and aldrin were detected. The calculated daily intake
      of DDT and HCH by the neonates exceeded their acceptable daily intake (ADI) set
      by the WHO. A statistically significant association was noted between alpha-HCH
      residues in milk and hemoglobin (Hb) level in maternal blood (P < 0.001). Also,
      there was a significant association between gamma-HCH and p,p'-DDT levels in milk
      and diastolic blood pressure of mother (P < 0.05). An apparent negative
      relationship between p,p'-DDE level in mother's milk and birthweight of the baby
      was also noticed (P < 0.05). These results highlight the need for periodic
      monitoring to determine organochlorine contamination in human milk and assess
      their impact on mother and on neonatal health.

PMID- 12046718
TI  - Different clinical features of amitraz poisoning in children.
AB  - OBJECTIVE: To evaluate clinical experience of amitraz poisoning in children.
      METHODS: In this study, the clinical and laboratory features of amitraz poisoning
      in 14 children are presented and compared with previous studies. RESULTS: This
      study revealed that clinical manifestations of poisoning by oral and dermal
      routes appeared within 30-150 min, and that central nervous system (CNS)
      depression, which is the most important sign, improved within 6-24 hours and
      other signs within 24-72 hours. Unlike the findings in other studies, three
      severe cases in our study had reversible mydriasis and one of them required
      resuscitation because of cardiopulmonary arrest occurring as a result of serious
      respiratory depression. In addition, hepatic function test levels had increased
      in these three cases, and aspiration pneumonitis existed because of emesis in two
      of them. CONCLUSION: There is little information in the literature about dermal
      poisoning. The signs and symptoms of dermal poisoning were relatively mild
      compared with oral poisoning, and there were no topical signs. The classical
      signs of alpha2-adrenergic stimulation such as marked sinusal bradycardia and
      mydriasis as reported in many poisoning cases of animals have not been reported
      before our three severe cases among children.

PMID- 12046720
TI  - Effects of prenatal exposure to combination of acetaminophen, isopropylantipyrine
      and caffeine on intrauterine development in rats.
AB  - The common effects of acetaminophen (paracetamol), isopropylantipyrine
      (propyphenazone) and caffeine on fetal development were examined in rats. The
      mixture was given in Tween 80 solution once daily, in a constant proportion of
      5:3:1, during days 8-14 of gestation in three different doses. Dose S1 - 3.5
      mg/kg acetaminophen, 2.14 mg/kg isopropylantipyrine, 0.7 mg/kg caffeine. Dose S2
      was 10 times higher, and S3 100 times higher than dose S1. On day 21 of
      gestation, the dams were sacrificed and the fetuses were removed. The corpora
      lutea, resorptions, live and dead fetuses were counted. The pre- and
      postimplantation mortality were calculated. The weight of fetuses and placentas,
      and the length of fetuses and their tails were measured. Two-thirds of each
      litter was processed for Alizarin Red S staining. The remaining third was fixed
      in Bouin's solution for subsequent visceral examination by using modified
      Wilson's technique. A significant decrease in body weight in S1 group, and fetal
      length and placental weight in group S3 were recorded. A significant increase in
      tail length in group S2 was observed. The number of corpora lutea, fetuses,
      resorptions, preimplantation and postimplantation mortality did not exhibit any
      significant difference. Nonsignificant incidence of fetal anomalies was found.

PMID- 12046719
TI  - Effects of cigarette smoke with different tar contents on hepatic and pulmonary
      xenobiotic metabolizing enzymes in rats.
AB  - The effects of smoke from cigarettes with two different tar contents (32
      mg/cigarette, high tar, and 15 mg/cigarette, low tar) on hepatic and pulmonary
      monooxygenase (MO) activities (aniline 4-hydroxylase [AH]; aminopyrine N
      demethylase [AMND]; 7-ethoxyresorufin O-deethylase [EROD]; p-nitroanisole O
      demethylase [p-NAOD]), lipid peroxidation (LP) and reduced glutathione (GSH)
      levels and glutathione S-transferase (GST) activities toward several substrates
      (1-chloro-2,4-dinitrobenzene [CDNBI; 1,2-dichloro-4-nitrobenzene [DCNB];
      ethacrynic acid [EAA]; 1,2-epoxy-3-(p-nitrophenoxy)-propane [ENPP]) were
      determined in adult male rats. Adult male rats were exposed to smoke of high- or
      low-tar cigarettes five times a day, with 1-hour intervals, for 3 days in a
      chamber where smoke and fresh air lead alternatively and were killed 16 hours
      after the last treatment. Smoke of both high- and low-tar cigarettes (SHTCC and
      SLTCC) significantly increased hepatic and pulmonary EROD and p-NAOD activities
      compared to controls. However, the increase noted by SHTCC on pulmonary EROD
      activity was higher than that of SLTCC. Hepatic AMND and pulmonary AH activities
      were significantly increased only by SHTCC. LP level was significantly decreased
      and increased by SHTCC in liver and lung, respectively, whereas it remained
      unaltered by SLTCC. Only SHTCC significantly increased GSH level in liver. In the
      lungs, both SHTCC and SLTCC significantly increased GSH level to the same extent.
      Hepatic GST activity toward EAA was significantly increased by SHTCC but was
      significantly decreased by SLTCC. ENPP GST activity was significantly decreased
      by SHTCC and SLTCC in the livers. In the lungs, all the GST activities examined
      were significantly depressed by SHTCC whereas only GST activity toward DCNB was
      reduced significantly by SLTCC. These results reveal that the hepatic and
      pulmonary MOs and GSTs are differentially influenced by SHTCC and SLTCC in rats.

PMID- 12046721
TI  - Molybdenum in rat tissue.
AB  - Male rats were given 50 mg/kg molybdenum (Mo; as sodium molybdate) in drinking
      water for eight consecutive doses. The feeding of Mo was associated with an
      increased concentration of Mo in body tissues. The highest concentrations of
      metal were found in the kidney while it was least in blood cells. The
      accumulation was considered to be significant.

PMID- 12046722
TI  - Testicular and spermatotoxic effect of nitrate in mice.
AB  - A study was conducted with nitrate to assess the testicular and spermatotoxic
      effects in mice at doses to which human beings are exposed as well as at higher
      dose levels in the drinking water. Potassium nitrate was administered to mice at
      dose levels 90, 200, 500, 700 and 900 ppm for 35 days. There was no difference in
      the uptake of water in control and treated animals. The amount of nitrate intake/
      mouse/day calculated on the basis of water intake in the different groups ranged
      from 22.5 to 27, 50 to 60, 125 to 150, 175 to 210 and 225 to 270 mg/kg body
      weight. No changes were evident in the body weight, testicular, epididymal and
      accessory organ weight at all the dose levels tested, although a decline in sperm
      count and sperm motility along with an increase in abnormal sperm was noticed at
      900 ppm. The activity of marker testicular enzymes, mainly 17-beta hydroxysteroid
      dehydrogenase (17-betaHSD) and gamma glutamyl transpeptidase (gamma-GT),
      associated with specific cell types were altered. Histopathological changes
      including atrophy and disturbed spermatogenesis were observed only at the 900-ppm
      dose level. In conclusion, we can say that the testicular and spermatotoxic
      effects are observed only at the highest dose level, which is not likely to be
      encountered in the drinking water.

PMID- 12046723
TI  - Itraconazole- and fluconazole-induced toxicity in rat hepatocytes: a comparative
      in vitro study.
AB  - This current study was to investigate the in vitro cytotoxicity of rat
      hepatocytes induced by the antifungal drugs, itraconazole and fluconazole. Both
      antifungal drugs caused dose-dependent cytotoxicity. In vitro incubation of
      hepatocytes with itraconazole revealed significantly higher lactate dehydrogenase
      (LDH) leakage when compared to fluconazole. Phenobarbital pretreated hepatocytes
      contained significantly higher total cytochrome P450 content than the control
      hepatocytes. P450 content was reduced approximately 30% for both types of
      hepatocytes after 6 hours incubation. Interestingly, cytotoxicity of itraconazole
      was reduced significantly by phenobarbital pretreatment. Phenobarbital did not
      have any effect on the cytotoxicity induced by fluconazole. These results
      demonstrate the in vitro toxicity of hepatocytes induced by itraconazole and
      fluconazole that were expressed in a dose- and time-dependent manner.
      Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole
      induced but not fluconazole-induced cytotoxicity in vitro.

PMID- 12046724
TI  - Severe fenthion intoxications due to ingestion and inhalation with survival
      outcome.
AB  - Two cases of severe fenthion intoxication are presented. The first is a case of a
      psychiatric patient who attempted suicide with ingestion of the compound, and the
      second case was of a child exposed to the chemical agent by air spraying. Both
      patients were treated in the intensive care unit with atropine and pralidoxime
      and finally survived. Fenthion blood levels on admission were 2.7 and 0.95
      microg/mL, respectively. Different concentrations of pralidoxime were added to
      the first patient's poisoned serum in order to assess in vitro the effect of
      pralidoxime on cholinesterase reactivation. The clinical and toxicological data
      of the poisonings are discussed, as well as the potential therapeutic use of
      pralidoxime in organophosphate intoxication.

PMID- 12046725
TI  - Basic toxicological approach has been effective in two poisoned patients with
      amitraz ingestion: case reports.
AB  - Amitraz, a formamidine insecticide and acaricide used in veterinary practice,
      presents side effects in humans related to its pharmacological activity on alpha
      2-adrenergic receptors. There is little information available in the literature
      about the toxicology of the product in man and the treatment of this poisoning.
      In this report, the clinical and laboratory features of amitraz poisoning in two
      patients by a veterinary formulation also containing xylene are presented. The
      major clinical findings were unconsciousness, drowsiness, respiratory failure
      requiring mechanical ventilation, miosis, hypothermia and bradycardia. The
      laboratory findings were hyperglycemia, hypertransaminasemia and increased
      urinary output. Supportive management of this poisoning in humans is suggested in
      only a few articles and there is no specific antidote for the subsequent possible
      pharmacological effects of amitraz. In our two cases, we performed supportive
      treatment such as mechanical ventilation, atropine, gastric lavage, active
      carbon, oxygen and fluid administration. We concluded that the basic approach to
      the patient with amitraz poisoning, including initial stabilization to correct
      immediate life-threatening problems, treatment to reduce absorption and measures
      to improve elimination of the toxin, is effective.

PMID- 12046726
TI  - Inhibition of salivary enzymes by cigarette smoke and the protective role of
      glutathione.
AB  - Tobacco smoke is involved in the pathogenesis of several diseases regarding
      different body systems, mainly cardiovascular and respiratory in addition to its
      local toxic effect in the oral cavity. The noxious effects of smoke compounds
      justify the high incidence of periodontal diseases, caries, and neoplastic
      diseases of oral tissues in smokers. Some toxic components of tobacco smoke,
      unsaturated and saturated aldehydes, could interact with thiol rich compounds,
      leading to structural and functional modification of these molecules. Previous
      papers have demonstrated an in vitro significant decrease of some enzymatic
      activities, both in plasma and in saliva, following external addition of
      aldehydes or exposure to cigarette smoke (CS). Furthermore, the same studies
      underlined the protective effect exerted by the addition of glutathione (GSH)
      against the damaging role of smoke aldehydes. In this study some salivary enzymes
      (lactic dehydrogenase [LDH], aspartate aminotransferase [AST] and amylase), and
      total GSH were measured in 20 volunteers smokers, before and just after smoking a
      single cigarette. All enzymatic activities showed a significant inhibition
      following a single cigarette, probably due to the interaction between smoke
      aldehydes and -SH groups of the enzyme molecules. Moreover, the percentage of the
      enzymatic inhibition showed a negative correlation with the basal level of
      salivary GSH. Our results emphasize that not only one cigarette is sufficient to
      impair the salivary enzymatic activities but also strengthen the proposed
      protective role of GSH against the noxious biochemical effects of CS.

PMID- 12046727
TI  - A prospective study of thalamic deep brain stimulation for the treatment of
      movement disorders in multiple sclerosis.
AB  - The place for neurosurgical management of movement disorders in multiple
      sclerosis is unclear. To evaluate the potential benefits of unilateral thalamic
      deep brain stimulation (DBS) a prospective study was performed. Fifteen patients
      with confirmed MS and chronic, severe, drug-resistant movement disorders
      underwent stereotactic surgery to implant a thalamic DBS electrode using CT image
      guidance and intra-operative neurophysiological testing. The primary outcome
      measures were reduction in tremor severity and improvement in tests of hand
      function when the DBS electrode was turned on, 12 months after surgery. Secondary
      outcome measures included indices of disability, handicap, neuropsychological
      function and independence. Thirty-seven patients were assessed for treatment, but
      only 15 underwent surgery. In the 10 patients in whom implantation of the
      complete DBS system was carried out there was a significant reduction in the
      severity of tremor (p = 0.02) and improvement in hand function (p = 0.02). There
      were no benefits in any of the secondary outcome measures. Two patients had
      thalamocapsular haemorrhages at the site of electrode implantation and two had
      seizures in the follow-up period. Thalamic stimulation significantly reduced the
      tremor associated with MS and improved hand function in the targeted upper limb.
      However, there can be difficulties with identifying an optimal implantation site
      during operation, significant procedural morbidity and difficulty in predicting
      immediate outcome. It is also likely that the insignificant benefits of DBS on
      disability and handicap reflect persisting cerebeller dysmetria, and both the
      severity and diffuse nature of the disease process in this patient cohort.

PMID- 12046728
TI  - The advantages of frameless stereotactic biopsy over frame-based biopsy.
AB  - A comparison study is presented, which examines the outcome, complications and
      cost of stereotactic brain biopsy performed with a frameless versus a frame-based
      method. The technique of frameless stereotactic biopsy has been shown previously,
      in both laboratory and in vivo studies, to achieve a level of accuracy at least
      equal to frame-based biopsy. The investigators have validated the technique in a
      large clinical series. The frameless and frame-based series were concurrent,
      comprising 76 and 79 cases, respectively. The frameless stereotactic technique
      involved standard needle biopsy, targeted by an image-guidance system and
      directed by a novel rigid adjustable instrument-holder. Frame-based biopsies were
      performed with the CRW and Leksell systems. There were no significant differences
      in the demographics, lesion site, size and pathologies between the groups.
      Operating theatre occupancy and anaesthetic time were both significantly shorter
      for the frameless series than the frame-based series (p < 0.0001). In addition,
      the complication rate in the frameless biopsy series was significantly lower than
      in the frame-based series (p = 0.018). This resulted in lower ITU bed occupancy
      (p = 0.02), shorter mean hospital stay (p = 0.0013) and significant cost savings
      (p = 0.0022) for the frameless stereotactic biopsy group, despite the greater use
      of more expensive MRI in these cases. This comparison study demonstrates that the
      superior imaging, target visualization and flexibility of the technique of
      frameless stereotactic biopsy translates into tangible advantages for safety,
      time and cost when compared with the current gold-standard of frame-based biopsy.
      The principles are discussed and the authors propose a definition for the term
      'frameless stereotaxy'.

PMID- 12046729
TI  - Insertion of depth electrodes with or without subdural grids using frameless
      stereotactic guidance systems--technique and outcome.
AB  - Over recent years frameless stereotactic systems have begun replacing framed
      systems for many neurosurgical procedures. However, little has been published
      regarding the use of these systems to guide intracranial electrode implantation
      for epilepsy surgery patients. Here we report our experience utilising such a
      system to insert depth electrodes and subdural grid electrodes. The SteathStation
      Image-Guided System (SSIGS) (Sofamor Danek, Memphis TN.) was used to insert
      bilateral depth electrodes in 13 patients, of whom 5 also underwent the insertion
      of subdural grids or strip electrodes. Initially, a surgical plan based on an
      entry and target point on axial and sagittal images was performed for the
      insertion of electrodes. Navigational views, using three-planar images, were then
      performed to determine which structures the electrodes would pass through to be
      correctly placed in the amygdala and hippocampus. The correct site of electrode
      implantation was confirmed post-operatively by spiral CT scans in 4 patients
      (which were then co-registered to the pre-implantation MRI using a surface
      matching technique) and the other 9 patients by post-implantation MRI. The SSIGS
      was found to have a mean registration error of 2.0 mm (range 1.8-2.5) in 10
      cases; in the 3 cases where the error was greater than 2.5 mm a surfacemerge
      technique was used with a mean error 0.9 (0.8-1.00). The post-implantation MRI or
      CT-MRI co-registration confirmed an accurate electrode placement in the mesial
      temporal region in all cases. Seizure onset lateralisation was achieved in 11
      patients, all of whom went onto formal resections based on these results. The
      only long-term complication was a case of osteomyelitis which required removal of
      the bone flap. 73% of patients had an excellent seizure outcome. Frameless
      stereotactic systems can be safely used to intracranial electrodes, avoid the
      disadvantages of the framed system and have the added advantage of the surgeon
      being able to visualise the trajectory and to adjust this to avoid vital
      structures. As well they eliminate surgical obstruction to the insertion of
      subdural grids at the same operation, which may be caused by a framed system.

PMID- 12046730
TI  - Long-term outcome in patients with central neurocytoma following stereotactic
      biopsy and radiation therapy.
AB  - Total excision is usually the recommended treatment for central neurocytomas. The
      role of radiation therapy in their management is controversial, and is usually
      reserved for partially resected or recurrent tumours. Long-term outcome was
      studied in patients with central neurocytoma who were treated with radiation
      therapy. By retrospective chart review, eight patients with intraventricular
      tumours, who had undergone radiation therapy following stereotactic biopsy, were
      identified. The diagnosis of neurocytoma was confirmed based on positive
      immunostaining with synaptophysin. Clinical and radiological follow-up was
      obtained. Of eight patients, one died 5 years after treatment from shunt
      dysfunction and 1 had disseminated intracranial disease 15 months after
      treatment. Six patients were symptom-free at a mean follow-up period of 78 months
      and had good local control as demonstrated by CT. Since this tumour can be
      confused with an oligodendroglioma or an ependymoma on routine histopathology (as
      happened in seven of our cases); immunohistochemical studies with synaptophysin
      should be routinely performed for intraventricular glial tumours. Our study
      supports the beneficial effect of radiation therapy in the management of these
      tumours.

PMID- 12046731
TI  - Giant pituitary adenomas: clinical characteristics and surgical results.
AB  - Although most pituitary neoplasms are benign, some grow rapidly, spreading to
      extrasellar tissues. Definition of these 'giant' pituitary adenomas (PAs) is not
      clear. In order to clarify this question, we studied all pituitary macroadenomas
      operated in our hospital during the last 20 years, differentiating those with
      diameter > or = 3 cm (n = 43) and attempting to identify their typical features
      and prognosis. The reason for consultation was local in 58.3% of giant PAs,
      hormonal in 22.9% and tumour recurrence in 16.7%. Surgery was performed via a
      trans-sphenoidal approach in 92.5% of cases and succeeded in completely removing
      the tumour in only 27% of cases. In conclusion, we found that giant PAs are not a
      special type but the extreme case in the gradient of invasiveness of tumours of
      adenohypophyseal origin. They are characterized by a higher frequency of neuro
      ophthalmological symptoms and hormonal deficits, and poorer response to surgical
      treatment.

PMID- 12046732
TI  - Epidemiology of adult brain tumours in Great Britain and Ireland.
AB  - The objective of this study was to review published reports on the epidemiology
      of primary brain tumours in adults and present the body of knowledge related to
      these tumours in Great Britain and Ireland. A literature search of all published
      epidemiological data on brain tumours was conducted in Pre-Medline, Medline,
      Embase and the Cochrane databases from 1966 to the present. A hand search of all
      the references alluded to was conducted and older studies identified. The
      articles were reviewed and tabulated. The papers were subjected to descriptive
      analysis. Information available to the public and held with the Cancer Registries
      was reviewed, and cross-referenced with published evidence. To our knowledge,
      only seven papers have discussed the epidemiology of primary brain tumours in
      adults. The different methodology of the population-based studies of brain
      tumours and the different time periods they investigated makes them incomparable.
      Two papers with comprehensive and detailed strategies for case ascertainment have
      both recorded tumour incidences of 21 per 100,000 person years. The results of
      the better studies are at variance with reports from the Cancer Registries. On
      the basis of the current studies, Cancer Registries appear to under-estimate the
      incidence of such tumours in adults. It is apparent that a significant number of
      tumours especially benign varieties are not recorded by some Cancer Registries.
      The previous estimates, patterns of incidence, prevalence, and survival of brain
      tumours in Great Britain and Ireland, may thus be incorrect. Patterns of primary
      brain tumours in adults have not been widely reported in GB and Ireland and the
      aetiology remains largely unknown. The need for current estimation of
      geographical and secular variations was identified. This demands closer co
      operation between medical and allied staff, and the Cancer Registries.
      Prospective regional studies of incidence patterns and up to date epidemiological
      appraisal is deemed necessary. Meanwhile, Cancer Registries should seriously
      consider the inclusion of all primary brain tumours in their database.

PMID- 12046733
TI  - A comparison of magnetic resonance imaging and neurophysiological studies in the
      assessment of cervical radiculopathy.
AB  - Neurophysiological studies (NPS) are often used by both neurosurgeons and
      neurologists to supplement neuroimaging findings in the diagnosis of cervical
      radiculopathy and in operative decision-making. The aim of this study was to
      assess whether nerve conduction and electromyographic studies added significant
      information to that obtained from high resolution MRI to warrant routine use.
      Over the 10-year period (1991-2001), we identified 48 patients who underwent both
      preoperative NPS and MRI for cervical radiculopathy. Sensitivity of MRI and NPS
      for diagnosing cervical radiculopathy was 93 and 42%, respectively. Whilst the
      positive predictive values for MRI and NPS were similar (91% versus 86%), the
      former had a higher negative predictive value (25% versus 7%). In only one case
      was the decision to operate based on NPS despite a negative MRI. We therefore
      suggest that in patients with clinical and MRI evidence of cervical
      radiculopathy, NPS has limited additional diagnostic value.

PMID- 12046734
TI  - Expression of ET(A) and ET(B) receptor mRNA in human cerebral arteries.
AB  - The vascular effects of endothelins (ET) are in mammals mediated via two receptor
      subtypes, endothelin A (ET(A), mainly constrictive) and endothelin B (ET(B),
      mainly dilating) receptors. We have examined the presence of ET(A) and ET(B)
      receptor mRNA using the reverse transcription polymerase chain reaction (RT-PCR)
      in both normal human cerebral arteries and cerebral arteries from patients with
      cerebrovascular disease. Two vessel preparations were studied: macroscopic
      arteries and microvessels, the latter obtained through a sensitive separation
      method. In endothelial cells both ET(A) and ET(B) receptor mRNA was detected. In
      almost all samples from normal cerebral arteries only ET(A) receptor mRNA was
      detected, whereas in vessel samples from patients with cerebrovascular disease as
      well as cerebral neoplasms, additional ET(B) receptor mRNA was detected
      significantly more frequently. The pathophysiological significance of this
      difference is at present speculative, but does point to a vascular involvement of
      this receptor in cerebrovascular disease.

PMID- 12046735
TI  - Atlantoaxial rotatory subluxation in skeletally immature patients.
AB  - Treatments of atlanto-axial rotatory subluxation in children are generally
      conservative. Previous reports have proposed that surgical treatment be reserved
      for fixed rotatory subluxation of more than 3 months duration, irreducible
      deformity or cases of recurrence. Six skeletally immature patients with Fielding
      type III atlanto-axial rotatory subluxation were treated conservatively with or
      without subsequent atlanto-axial arthrodesis. The follow-up period for all the
      cases exceeded 18 months. Results and outcomes were analysed with an emphasis on
      the delay until diagnosis, causes of delays in diagnosis and factors influencing
      the necessity of surgical intervention. Neither mortality nor major morbidity was
      noted in any cases in this study. In our experience, type III fixed rotatory
      subluxation of 6 weeks duration will potentially recur. We recommend early
      surgery for type III fixed rotatory subluxation of more than than 3 months'
      duration, with atlanto-axial arthrodesis being a safe and effective procedure in
      children.

PMID- 12046737
TI  - 'Look beneath the stockings'--delayed diagnosis of ankle fractures in patients
      with thoracic cord compression.
AB  - Two patients with thoracic cord compression and ankle fractures are presented.
      The diagnosis and treatment of the ankle fractures was delayed in these patients.
      The lack of pain sensation in the lower limbs and the use of TED stockings that
      covered the area of abnormality were the reasons for the delayed diagnosis.

PMID- 12046736
TI  - Dissecting aneurysm confined to the anterior cerebral artery.
AB  - Dissecting aneurysm confined to the anterior cerebral artery (ACA) is extremely
      rare. Four patients presented with dissecting aneurysms confined to the ACA, two
      with cerebral infarctions in the territories of the ACA and two with subarachnoid
      haemorrhages. The two patients with infarction were treated by conservative
      therapy with anti-platelet therapy and the two patients with subarachnoid
      haemorrhage were treated by wrapping surgery in the early period after the ictus.
      Conservative treatment for patients with infarction and early wrapping surgery
      for patients with subarachnoid haemorrhage are recommended.

PMID- 12046738
TI  - Excision of large solid haemangioblastomas of the cerebellopontine angle by a
      skull base approach.
AB  - Solid haemangioblastomas can be difficult to treat surgically because of their
      hypervascularity and requirement for circumferential dissection. We report two
      cases of large solid cerebellopontine angle haemangioblastomas that were safely
      resected utilizing wide transtemporal posterolateral skull-base exposures. In
      both cases, good tumour exposure was achieved with trans-cochlear approaches and
      division of the sigmoid sinus. These were large tumours and we felt that the
      added complexity of the approach was justified by providing panoramic exposure to
      allow safe resection.

PMID- 12046739
TI  - Brain stem cavernoma excised by subtemporal-infratemporal approach.
AB  - Brain stem cavernomas are most safely removed through the pial surface at which
      the cavernoma is surfacing. When a lower pontine or an upper medullary cavernoma
      comes to the surface of the anterior portion of the brain stem, it is difficult
      to reach by traditional approaches. We describe a case of mid- and lower pontine
      cavernoma, surfacing anteriorly, which was completely excised by the subtemporal
      infratemporal approach. After making a small temporal craniotomy and a zygomatic
      osteotomy, the petrous carotid artery was mobilized anteriorly and the
      petroclival bone was drilled away to reach the anterior surface of the pons using
      the subtemporal-infratemporal approach. A small incision was made on the anterior
      surface of the pons, between the CN V and CN VI and the cavernoma was completely
      excised with the aid of the surgical microscope and the neuro-endoscope.
      Immediately after the operation, the patient had a complete abducens palsy and a
      mild increase of left hemiparesis, both of which resolved completely within 3
      months. The patient returned to the full time work without any neurological
      deficit. A follow-up MRI 1 year later showed the complete excision of the
      cavernoma. The subtemporal-infratemporal approach is useful for anteriorly
      located mid to lower pontine and upper medullary cavernomas.

PMID- 12046740
TI  - Episodic facial palsy due to epithelial cyst of the cerebellopontine angle: case
      report and review of the literature.
AB  - A case of cerebellopontine angle epithelial cyst is described. Lesions in this
      region usually present with hearing loss, tinnitus, dysequilibrium, headaches,
      facial numbness and occasionally trigeminal neuralgia. Our patient presented with
      the unusual phenomenon of episodic facial palsy. The literature reporting this
      lesion as well as this mode of presentation has been reviewed.

PMID- 12046741
TI  - Sacral perineural cysts: imaging and treatment options.
AB  - Perineural cysts are an uncommon radiological finding and a rare cause of
      radicular leg pain. We report the clinical findings, imaging and operative
      appearances of a patient who presented with radicular leg and perineal pain,
      which was found to be associated with multiple sacral perineural cysts. The
      diagnostic and treatment options are explored. In particular, the use of
      percutaneous fine-needle cyst drainage as a guide to the value of surgery is
      discussed. Postoperative complications, such as pseudomeningocoele can occur, but
      may be effectively treated with lumbar drainage.

PMID- 12046742
TI  - Intracranial neurenteric cysts: a report of two cases.
AB  - Neurenteric or enterogenous cysts are rare, congenital, benign lesions of the
      central nervous system. Not more than 35 case reports of neurenteric cysts
      occurring in the cranial cavity have been documented. We describe two cases of
      intracranial neurenteric cysts.

PMID- 12046743
TI  - Spontaneous extradural haematoma associated with craniofacial infections: case
      report and review of the literature.
AB  - A 17-year-old male with occult cleft palate presented with depressed
      consciousness due to spontaneous frontal extradural haematoma associated with
      sinusitis. Craniotomy, evacuation of the haematoma and drainage of the frontal
      sinuses led to a full recovery. Spontaneous extradural haematomas secondary to
      craniofacial infections are very rare; this appears to be the first described
      with a coexisting congenital palatal abnormality. The diagnosis should be
      considered when signs of infection are present with depressed consciousness as a
      delay in treatment may result in death.

PMID- 12046744
TI  - Life-threatening intra-abdominal haemorrhage following insertion of a
      lumboperitoneal shunt.

PMID- 12046745
TI  - Neurosurgical management of paediatric germ cell tumours of the central nervous
      system--a multi-disciplinary team approach for the new millennium.

PMID- 12046746
TI  - Acute subdural haematoma in a boxer.
AB  - On the basis of the judgements of the Court of First Instance, and of the Court
      of Appeal, (Michael Alexander Watson versus British Board of Control Limited) the
      causation aspects of two sequential acute subdural haematomas sustained by a
      boxer, are critically examined. The beneficial effects in this case of
      'resuscitation' at the ringside, and its feasibility, are very doubtful. So also
      are the practicability and benefit of direct transfer to a neurosurgical
      department, with the timing of operation being advanced by some 45 minutes, or
      more probably by only 15 minutes.

PMID- 12046747
TI  - Brief history of the National Committee on Radiation Protection and Measurements
      (NCRP) covering the period 1929-1946. 1958.

PMID- 12046749
TI  - History of the International Commission on Radiological Protection (ICRP). 1958.

PMID- 12046748
TI  - Radiation exposure as a reasonable calculated risk. 1958.

PMID- 12046750
TI  - Health physics instrument's shadow.

PMID- 12046751
TI  - Transfer of 131I into human breast milk and transfer coefficients for
      radiological dose assessments.
AB  - Data on transfer of radioiodine into human milk are rare in the literature. Data
      from sixteen publications were reviewed and analyzed to estimate the transfer
      coefficient (f(hm)*, having units of d L(-1)). The data on the radioiodine
      concentration in breast milk were analyzed by two methods: direct numerical
      integration and integration of a fitted exponential model. In general, the
      integrated fitted functions were greater. The fitted functions likely better
      describe the transfer into milk since few data sets sampled mothers' milk near
      the time of maximum excretion. The derived transfer coefficient values seem to
      represent two populations. The first group was those individuals who had very low
      excretions, including those where thyroid and mammary uptake was impaired by the
      administration of stable iodine or iodinated compounds. The second group included
      those with much higher excretions. The second group, termed the "normal
      excretion" group, had transfers of iodine to milk that were more than ten-fold
      higher than in the "low-excretion" group. The derived milk transfer coefficient
      data for the low- and normal-excretion groups fitted to lognormal distributions
      gave geometric means, (geometric standard deviations), of 0.043 d L(-1) (2.1, n =
      14) and 0.37 d L(-1) (1.5, n = 12), respectively. Estimates of the effective half
      time (time from maximum concentration to half the value) were determined for the
      low- and normal-excretion groups separately. There was evidence that the
      effective half-time was longer for the normal- than for the low-excretion group;
      the geometric mean (and geometric standard deviation) were 12 (1.7) and 8.5 (2.6)
      h, respectively, though the difference was not statistically significant. The
      geometric mean times to maximum milk concentration in the low- and normal
      excretion groups were nearly identical, 9.4 (3.1) and 9.0 (1.6) h, respectively.
      The data show that administration of large doses of stable iodine (commonly used
      to block uptake of iodine into the thyroid) is also an effective means to block
      radioiodine transfer into milk. Thus, protecting the mother's thyroid also
      protects the nursing infant. Despite inadequacies of available data describing
      the transfer of radioiodine to human milk within a healthy population of women,
      the values of f(hm)* provided here are believed to be the best available for use
      in radiological assessments. These values are particularly applicable to
      lactating women having normal diets and availability to stable iodine, as in the
      United States.

PMID- 12046752
TI  - Age-specific uncertainty in particulate deposition for 1 microm AMAD particles
      using the ICRP 66 lung model.
AB  - The ICRP 66 lung model may be used to determine age-specific dose estimates for
      members of the public via the inhalation pathway. A significant source of
      uncertainty in internal dosimetric modeling is due to particulate deposition in
      regions of the respiratory tract. Uncertainties in estimates of particulate
      deposition are present because of the inherent variability in the deposition
      model and its various input parameters. An improved understanding of the
      uncertainty in particulate deposition will further guide research efforts and
      improve our ability to quantify internal dose estimates. The ICRP 66 lung
      deposition model is most sensitive to breathing rate when 1 microm AMAD particles
      are inhaled by members of the public. Uncertainties in deposition fractions are
      shown to span an order of magnitude with their distributions varying by age and
      sex for a particular lung region. Age-specific uncertainties of deposition
      fraction demonstrate increased estimates of extrathoracic deposition in younger
      age groups due to the decreased size of the respiratory tract airways. This age
      specific trend becomes more pronounced for very young children and infants. The
      largest fractional deposition occurs in the alveolar and extrathoracic regions,
      regardless of age and sex.

PMID- 12046753
TI  - Dose estimate of inhaled hafnium tritide using the ICRP 66 lung model.
AB  - Metal tritide is widely used for research, purification, compression, and storage
      of tritium. The current understanding of metal tritide and its radiation
      dosimetry for internal exposure is limited, and ICRP publications do not provide
      the tritium dosimetry for hafnium tritide. The current radiation protection
      guidelines for metal tritide particles (including hafnium tritide) are based on
      the assumption that their biological behavior is similar to tritiated water,
      which is completely absorbed by the body. However, the solubility of metal
      tritide particles depends on the chemical form of the material. The biological
      half-live of hafnium tritide particles and the dosimetry of an inhalation
      exposure to those particles could be quite different from tritiated water. This
      paper describes experiments on the dissolution rate of hafnium tritide particles
      in a simulated lung fluid. The results showed that less than 1% of the tritium
      was dissolved in the simulated lung fluid for hafnium tritide particles after 215
      d. The short-term and long-term dissolution half times were 46 and 4.28 x 10(5)
      d, respectively. This indicates that hafnium tritide is an extremely insoluble
      material. Self-absorption of beta rays in the hafnium tritide particles was
      estimated by a numerical method. The dose coefficients were calculated as a
      function of particle size using in vitro solubility data and a calculated self
      absorption factor. The dose coefficient decreased with aerodynamic diameters in
      the range of 0.25 to 10 microm, mainly because the self-absorption factor
      decreased with increasing particle size. For a particle 1 microm in aerodynamic
      diameter, the dose coefficient of a hafnium tritide particle was about 10 times
      higher than that of tritiated water but was about 1.4 times lower than that
      calculated by ICRP Publication 71 for Type S tritiated particles. The ICRP
      estimate did not include a self-absorption factor and thus might have
      overestimated the dose. This finding has significant implications for current
      health protection guidelines.

PMID- 12046754
TI  - Assessment of the aversion coefficient in nuclear safety in Hungary.
AB  - The key elements of the optimization practice as applied to radiation protection
      are the monetary value of the averted person-sievert and the aversion
      coefficient. Determination of the monetary value of the unit averted person
      sievert (as alpha(base)-parameter) in Hungary was presented in a previous paper.
      The estimation of this parameter was carried out by the willingness-to-pay (WTP)
      method associated with averted occupational exposure (at the NPP Paks/Hungary).
      The aversion coefficient predicts the importance of dose reduction based on the
      magnitude of the dose. The assessment of the aversion coefficient occurred also
      by means of the WTP method in the spring of 2000. Its value has been estimated on
      the basis of individual preferences concerning the distribution of individual
      exposure in nuclear safety. The results achieved by the WTP among the radiation
      specialists from the NPP Paks, Hungary, assessed a value for the aversion
      coefficient of 1.86 over the whole range of individual exposure levels. This
      value is a bit greater than the value obtained in France (1.7) and the higher
      coefficient expresses a higher priority to reduce the highest individual
      exposures.

PMID- 12046755
TI  - External exposure model in the RESRAD computer code.
AB  - An external exposure model has been developed for the RESRAD computer code that
      provides flexibility in modeling soil contamination configurations for
      calculating external doses to exposed individuals. This model is based on the
      dose coefficients given in the U.S. Environmental Protection Agency's Federal
      Guidance Report No. 12 (FGR-12) and the point kernel method. It extends the
      applicability of FGR-12 data to include the effects of different source
      geometries, such as cover thickness, source thickness, source area, and shape of
      contaminated area of a specific site. A depth factor function was developed to
      express the dependence of the dose on the source thickness. A cover-and-depth
      factor function, derived from this depth factor function, takes into account the
      dependence of dose on the thickness of the source region and the thickness of the
      cover above the source region. To further extend the model for realistic
      geometries, area and shape factors were derived that depend not only on the
      lateral extent of the contamination, but also on source thickness, cover
      thickness, and radionuclides present. Results obtained with the model generally
      compare well with those from the Monte Carlo N-Particle transport code.

PMID- 12046756
TI  - Simulations of neutron transport at low energy: a comparison between GEANT and
      MCNP.
AB  - The use of the simulation tool GEANT for neutron transport at energies below 20
      MeV is discussed, in particular with regard to shielding and dose calculations.
      The reliability of the GEANT/MICAP package for neutron transport in a wide energy
      range has been verified by comparing the results of simulations performed with
      this package in a wide energy range with the prediction of MCNP-4B, a code
      commonly used for neutron transport at low energy. A reasonable agreement between
      the results of the two codes is found for the neutron flux through a slab of
      material (iron and ordinary concrete), as well as for the dose released in soft
      tissue by neutrons. These results justify the use of the GEANT/MICAP code for
      neutron transport in a wide range of applications, including health physics
      problems.

PMID- 12046757
TI  - Micrometer-sized short-lived radioactive aerosol particles for convenient use in
      laboratory measurements.
AB  - For calibration and testing of radioactive aerosol measuring equipment such as
      continuous air monitors and cascade impactors, and other research applications,
      it is helpful to have a convenient and relatively safe means of producing
      radioactive aerosol particles of controlled size and activity. We describe a
      technique for producing such particles in the micrometer-diameter size range
      using electrostatic deposition of radon decay products onto otherwise
      nonradioactive powders of different sizes. An electric field focuses radon decay
      products (primarily 218Po) onto the surface of a powdered substrate that is then
      suspended by a technique such as pneumatic dry dispersion. Only a modest-activity
      commercial 222Rn source (e.g., containing as little as 10(5) Bq of 226Ra) is
      required, and issues of radioactive cleanup and contamination are minimized due
      to the short half-lives (26.8 min or less) of the decay products. We report
      representative results using powders of glass beads, iron oxide, and iron and
      gold metals in the size range of 0.3 to 30 microm. Yields for the deposited
      radioactivity per unit concentration of 222Rn gas were of the order of 5 x 10(-7)
      Bq (214Bi) per milligram substrate per Bq m(-3) of 222Rn for an electrostatic
      collection time of 30 min.

PMID- 12046758
TI  - Thresholds for retinal injury from multiple near-infrared ultrashort laser
      pulses.
AB  - Multiple-pulse lasers are routinely used in the laboratory for research,
      manufacturing, medical procedures, and in military applications. In order to
      provide a safe work environment for personnel using these lasers, safety
      standards have been established and have been in use for many years. These safety
      standards have addressed laser pulses of nanosecond duration and longer.
      Recently, safety standards have been updated to address laser pulses as short as
      100 femtoseconds in duration. In order to tie these "ultrashort" laser pulses to
      hazard trends in currently established standards for multiple-pulse exposures
      with repetition rates less than several kilohertz, this experiment was conducted.
      Reported herein are minimum visible lesion thresholds in the paramacula of the
      primate retina using an 800-nm wavelength laser with 1,000 pulses per second, at
      130 femtoseconds (fs) pulse duration. The minimum visible lesion (MVL) thresholds
      were determined at 1 h and 24 h post exposure for 1, 10, 100, 1,000, and 10,000
      pulses and are compared with thresholds reported by other researchers. These new
      data are evaluated relative to the current safety standards for retinal exposure
      limits as a function of the number of pulses for femtosecond-pulse duration. Data
      from this study show that the retinal ED50 thresholds/pulse in the paramacula
      decrease by almost a factor of four as the number of pulses goes from one to ten
      and then decrease very little for an increase of three decades more in the number
      of pulses. The MVL-ED50 at the threshold decreased from 0.55 microJ for a single
      pulse to 0.15 microJ/pulse for 10 pulses and then only to 0.11 microJ/pulse for
      10,000 pulses.

PMID- 12046759
TI  - Formation and retention of organically bound deuterium in rice in deuterium water
      release experiment.
AB  - As a substitute of tritium, deuterated water (D2O) vapor release experiments were
      performed in a greenhouse to estimate the different formation and subsequent
      retention of organically bound deuterium in rice plants between daytime and
      nighttime exposure. Potted rice plants were exposed to D2O vapor in the
      greenhouse for 8 h, under day or night conditions. Deuterium concentrations in
      free water and organic matter in rice leaves and ears were investigated until
      harvest time. The formation of organically bound deuterium in the daytime was
      higher than during the nighttime by the factors of 2.4 for the ear and 2.9 for
      the leaf. The decrease of the organically bound deuterium concentration in the
      ear after the nighttime exposure was faster than that after the daytime exposure.
      Data analysis was carried out using a compartment model in which different
      generating processes of organic matter were considered. The calculated
      organically bound deuterium retention in rice agreed with the measured value.

PMID- 12046760
TI  - Measurement of outdoor terrestrial gamma radiation in the Sultanate of Oman.
AB  - The terrestrial gamma radiation level was determined throughout the Sultanate of
      Oman over a 3-y period. The dose rate at 1 m above the ground was measured at 512
      locations using a compensated Geiger-Miller detector. The activity concentration
      of soil/rock samples, collected from 112 locations, was determined by gamma
      spectrometry. Dose rates calculated from the activity concentrations compared
      well with the measured values corrected for the cosmic ray contribution. Some of
      the highest terrestrial dose rates, up to 110 nGy h(-1), were measured in shales
      (Wadi Bani Awf, Saih Hatat, and the Huqf) and exposed basement granites (Jebal
      Jalan and the Mirbat peninsula). Two small hot spots were found where the maximum
      dose rate was 1,024 nGy h(-1). The average dose rate in the main population area
      of the Batinah is 38.5 nGy h(-1) (0.29 mSv y(-1)) and Muscat 44.9 nGy h(-1) (0.34
      mSv y(-1)). The mean population weighted dose rate is 39.8 nGy h(-1) (0.30 mSv y(
      1)). Most of Oman's surface rock is limestone, which is low in concentrations of
      radionuclides from the uranium and thorium series. Hence, the average dose rate
      is well below the world average of 0.45 mSv y(-1).

PMID- 12046761
TI  - Measuring skin dose with radiochromic dosimetry film in the cardiac
      catheterization laboratory.
AB  - A new radiochromic dosimetry film was tested to determine its potential for
      patient skin dose monitoring in a fluoroscopically intensive environment such as
      the cardiac catheterization laboratory. The dose, time, energy, dose
      fractionation, dose rate, and sheet to sheet uniformity response were tested. All
      tests support the conclusion that this is a simple, noninvasive, retrospective
      method to identify skin regions at risk from high x-ray doses. The consistency
      and accuracy of dose measurements allow for an estimation of the localized skin
      dose to those patients who are susceptible to radiation induced skin injury.

PMID- 12046762
TI  - Modeling radionuclide effluxes from agricultural and natural ecosystems in
      Belarus.
AB  - A mathematical model is described which is appropriately constructed to calculate
      effluxes of radionuclides from agricultural and natural ecosystems. The
      application of this model is demonstrated by estimating effluxes in the Bragin
      region and in the Narovlya region in the Republic of Belarus both highly affected
      by the Chernobyl accident fallout. Depending on the nature of the area and the
      deposition, the total efflux and the exported radioactivity are calculated. It is
      shown that the exported radioactivity for natural foodstuffs represents more than
      64% (Bragin region) and 86% (Narovlya region) of the total 137Cs efflux, and for
      agricultural products 2.7% and 2.3%, respectively. The contribution of the
      different foodstuffs deriving from natural and agricultural used land to the
      individual and collective dose for 137Cs and 90Sr are estimated and presented. In
      the Bragin region for the collective annual dose the highest contribution is due
      to milk and meat consumption (137Cs) and flour and milk (90Sr), for individual
      annual dose milk and mushrooms (137Cs), and milk and flour (90Sr) contribute
      most. In the Narovlya region this contribution for the collective and individual
      annual dose is due to milk and mushroom consumption (137Cs) and flour and milk
      (90Sr).

PMID- 12046763
TI  - Alpha CAM alarm set points in a salt dust environment.
AB  - While considering the regulatory and site specific requirements for Continuous
      Air Monitor responses in the Waste Isolation Pilot Plant underground (which is a
      salt mine), a number of issues relating to the buildup of salt (NaCl) on the
      filters must be considered when determining the alarm set points. As the Waste
      Isolation Pilot Plant is a Department of Energy facility, alarm set point
      determination must be made in light of the regulatory drivers and physical
      limitations found when monitoring for airborne contamination in an underground
      salt mine. The use of dual alarm set points is also exploited to implement a
      graded approach to alarm responses.

PMID- 12046764
TI  - Internet-based display of remotely-acquired ambient radiation data.
AB  - The World-Wide Web is a powerful medium for disseminating radiation information
      in a readily and universally retrievable manner. Ambient monitoring of radiation
      measurements at a New York City location (Jacobi Hospital, Bronx, NY 10461), with
      automated publication of the data on the Web, has been ongoing since 1998.
      Several times daily, specialized communications software automatically retrieves
      the data by modem to a central base computer from where it is uploaded to an
      Internet-accessible Web page. The data are then accessible by standard Internet
      Web browser at the address www.aw-el.com/nyc/. This automated acquisition and
      display system has run with uninterrupted operation and minimal operator
      intervention for over 3 years. As the Internet becomes a ubiquitous conduit for
      information transmittal, the Web can serve as an effective means of display for
      radiation data, with relevance to many health physics applications discussed
      herein.

PMID- 12046765
TI  - Comments on "Risks of fatal cancer from inhalation of (239,240)plutonium by
      humans: a combined four-method approach with uncertainty evaluation".

PMID- 12046766
TI  - No depleted uranium in cruise missiles or Apache helicopter munitions--comment on
      an article by Durante and Pugliese.

PMID- 12046767
TI  - Treatment of subungual hematoma.

PMID- 12046768
TI  - Management of nail bed lacerations.

PMID- 12046769
TI  - An aspirin a day keeps the MI away (for some).

PMID- 12046770
TI  - Diagnosis and management of acute bronchitis.
AB  - Acute bronchitis is one of the top 10 conditions for which patients seek medical
      care. Physicians show considerable variability in describing the signs and
      symptoms necessary to its diagnosis. Because acute bronchitis most often has a
      viral cause, symptomatic treatment with protussives, antitussives, or
      bronchodilators is appropriate. However, studies indicate that many physicians
      treat bronchitis with antibiotics. These drugs have generally been shown to be
      ineffective in patients with uncomplicated acute bronchitis. Furthermore,
      antibiotics often have detrimental side effects, and their overuse contributes to
      the increasing problem of antibiotic resistance. Patient satisfaction with the
      treatment of acute bronchitis is related to the quality of the physician-patient
      interaction rather than to prescription of an antibiotic.

PMID- 12046771
TI  - Information from your family doctor. Acute bronchitis.

PMID- 12046772
TI  - Management of newborns exposed to maternal HIV infection.
AB  - The management of infants whose mothers are infected with the human
      immunodeficiency virus (HIV) involves minimizing the risk of vertical
      transmission of HIV, recognizing neonatal HIV infection early, preventing
      opportunistic infections, and addressing psychosocial issues. Maternal
      antiretroviral drug therapy during pregnancy and labor, followed by six weeks of
      neonatal zidovudine therapy, can significantly decrease the risk of vertical
      transmission. Additional antiretroviral drugs may be needed in some high-risk
      newborns. Elective cesarean section also may prevent vertical transmission of
      HIV. Virologic tests allow early diagnosis of HIV infection, facilitating the
      timely initiation of aggressive treatment and the prevention of opportunistic
      infections. Even when tests are negative, infants must be closely monitored until
      age 18 months to completely rule out HIV infection. Prophylaxis for Pneumocystis
      carinii pneumonia should be initiated when HIV-exposed infants are six weeks old
      and should be continued for at least four months, regardless of negative
      virologic tests, because P. carinii pneumonia is often the initial presentation
      of HIV infection in infants. Laboratory monitoring, screening for perinatal
      infections, appropriate social support, and other modifications of standard
      infant care are also necessary.

PMID- 12046773
TI  - Information from your family doctor. Preventing HIV infection in your baby.

PMID- 12046774
TI  - Double-ligature: a treatment for pedunculated umbilical granulomas in children.
AB  - Umbilical granulomas are common inflammatory reactions to the resolving umbilical
      stump. The double-ligature technique is simple to perform and provides good
      cosmetic and functional results with only minor complications. The granuloma
      becomes necrotic and drops off within seven to 14 days. The double-ligature is a
      preferable alternative to multiple topical applications of silver nitrate for the
      treatment of pedunculated umbilical granulomas in children.

PMID- 12046775
TI  - Diagnosis and treatment of Paget's disease of bone.
AB  - Paget's disease of bone (also known as osteitis deformans) is a nonmalignant
      disease involving accelerated bone resorption followed by deposition of dense,
      chaotic, and ineffectively mineralized bone matrix. The origin of the disease is
      unknown, and it is frequently asymptomatic; however, the patient may present with
      symptoms depending on the bones involved. The most common symptom is pain in the
      affected bone; neurologic, hearing, vision, cardiac, and oncologic complications
      are possible. Diagnosis is primarily made by radiographs. Bisphosphonates are the
      most common treatment.

PMID- 12046776
TI  - Abnormal uterine bleeding associated with hormonal contraception.
AB  - Millions of women in the United States use some type of hormonal contraception:
      combination oral contraceptive pills (OCPs), progestin-only pills,
      medroxyprogesterone acetate injections, or subdermal levonorgestrel implants.
      Abnormal uterine bleeding is a common but rarely dangerous side effect of
      hormonal contraception. It is, however, a major cause for the discontinuation of
      hormonal contraception and the resultant occurrence of unplanned pregnancy. The
      evaluation of abnormal uterine bleeding in women who are using hormonal
      contraception includes an assessment of compliance, a thorough history and
      complete physical examination to exclude organic causes of bleeding, and a
      targeted laboratory evaluation. Pregnancy and the misuse of OCPs are frequent
      causes of abnormal uterine bleeding. Bleeding is common during the first three
      months of OCP use; counseling and reassurance are adequate during this time
      period. If bleeding persists beyond three months, it can be treated with
      supplemental estrogen and/or a nonsteroidal anti-inflammatory drug (NSAID). Other
      options are to change to an OCP with a higher estrogen content or to a different
      formulation (i.e., a low-dose OCP containing a different progestin). Management
      strategies for women with abnormal uterine bleeding who are using progestin-only
      contraceptive methods include counseling and reassurance, as well as the
      administration of supplemental estrogen and/or an NSAID during bleeding episodes.

PMID- 12046777
TI  - Information from your family doctor. Birth control pills and bleeding.

PMID- 12046778
TI  - Proper use of child safety seats.
AB  - Motor vehicle crashes continue to be the leading cause of death in children one
      to 14 years of age. Used correctly, child safety seats significantly reduce child
      morbidity and mortality. Although many parents know child safety seats are
      important, more than 80 percent of seats are misused. Increased education of
      parents regarding proper use of child safety seats can protect children from
      potentially fatal crash forces. Parents may also be educated about community
      resources and the several types of child safety seats.

PMID- 12046779
TI  - Topical treatment of common superficial tinea infections.
AB  - Tinea infections are superficial fungal infections caused by three species of
      fungi collectively known as dermatophytes. Commonly these infections are named
      for the body part affected, including tinea corporis (general skin), tinea cruris
      (groin), and tinea pedis (feet). Accurate diagnosis is necessary for effective
      treatment. Diagnosis is usually based on history and clinical appearance plus
      direct microscopy of a potassium hydroxide preparation. Culture or histologic
      examination is rarely required for diagnosis. Treatment requires attention to
      exacerbating factors such as skin moisture and choosing an appropriate antifungal
      agent. Topical therapy is generally successful unless the infection covers an
      extensive area or is resistant to initial therapy. In these cases, systemic
      therapy may be required. Tinea corporis and cruris infections are usually treated
      for two weeks, while tinea pedis is treated for four weeks with an azole or for
      one to two weeks with allylamine medication. Treatment should continue for at
      least one week after clinical clearing of infection. Newer medications require
      fewer applications and a shorter duration of use. The presence of inflammation
      may necessitate the use of an agent with inherent anti-inflammatory properties or
      the use of a combination antifungal/steroid agent. The latter agents should be
      used with caution because of their potential for causing atrophy and other
      steroid-associated complications.

PMID- 12046780
TI  - Aspirin for the primary prevention of cardiovascular events: recommendations and
      rationale.

PMID- 12046781
TI  - Information from your family doctor. HIV: coping with the diagnosis.

PMID- 12046782
TI  - Information from your family doctor. HIV in women.

PMID- 12046783
TI  - Information from your family doctor. HIV and pregnancy.

PMID- 12046785
TI  - Prevalence of feline leukaemia virus and antibodies to feline immunodeficiency
      virus and feline coronavirus in stray cats sent to an RSPCA hospital.
AB  - A total of 517 stray cats at an RSPCA veterinary hospital were tested for feline
      leukaemia virus (FeLV), feline coronavirus (FCoV) and feline immunodeficiency
      virus (FIV). The prevalence of FeLV was 3.5 per cent in all the cats, 1.4 per
      cent in healthy cats and 6.9 per cent in sick cats. FeLV positivity was
      associated only with disease of non-traumatic origin. Antibodies to FCoV were
      present in 22.4 per cent of the cats, and their prevalence was significantly
      higher in cats over two years old and in feral/semiferal cats. The prevalence of
      antibodies to FIV was 10.4 per cent in all the cats, 4.9 per cent in healthy cats
      and 16.7 per cent in sick cats. The prevalence of FIV antibodies was
      significantly higher in entire males and neutered males than in females, in cats
      over two years old compared with younger cats, and in cats suffering disease of
      non-traumatic origin rather than in healthy cats or cats suffering only from
      trauma. Sex, age and health status were each independently highly associated with
      FIV antibodies.

PMID- 12046786
TI  - Evaluation of the portable Cepheid SmartCycler real-time PCR machine for the
      rapid diagnosis of foot-and-mouth disease.
AB  - The ability of the portable Cepheid SmartCycler real-time PCR machine to detect
      foot-and-mouth disease (FMD) virus sensitively and accurately was evaluated by
      comparing the results of the analyses of nasal swab and serum samples from
      experimentally infected animals with those obtained from the real-time PCR assay
      currently in use in the laboratory. The results indicated that the ability of the
      machine to detect viral RNA is greatly affected by the PCR reagents used for the
      assay. When it was used with PCR beads it was unable to detect weakly positive
      samples, but when TaqMan core reagents were used for the assay, its sensitivity
      was significantly increased. The machine could be used for the laboratory-based
      detection of FMD; however, as with all assays, significant optimisation of assay
      conditions as well as solid validation of the technique is required.

PMID- 12046784
TI  - ACOG practice bulletin on thyroid disease in pregnancy.

PMID- 12046787
TI  - Pathological changes of renal tubular dysplasia in Japanese black cattle.
AB  - Pathological studies were conducted on 91 Japanese Black cattle with a hereditary
      disease which induced growth retardation, long hooves and renal failure. In
      calves one to two months old, no gross abnormalities were observed in the
      kidneys, but microscopical examinations revealed immature epithelia which were
      arranged irregularly and not attached to the basement membranes in some proximal
      tubules. In animals three to 36 months old, the kidneys had shrunk perceptibly
      and had grey-white radial streaks; microscopically they showed severe
      interstitial fibrosis with round-cell infiltration in the outer zone of the
      medulla and cortex, and reductions in the numbers of glomeruli and tubules. In
      the fibrotic areas there were immature epithelia with an irregular arrangement,
      and the basement membrane of the tubules was thickened. It was concluded that
      renal tubular dysplasia was the primary lesion of the disease, and that
      interstitial fibrosis and reductions in the numbers of nephrons were secondary
      lesions.

PMID- 12046789
TI  - Survey of Johne's disease in imported animals in the Republic of Ireland.

PMID- 12046788
TI  - Use of height-specific weigh tapes to estimate the bodyweight of horses.
AB  - Two thousand horses of different ages, heights and breeds were divided into two
      height groups of up to 14.2 hands high (hh) and more than 14.2 hh, and weighed on
      a weighbridge; each horse then had its weight estimated by three weigh tapes, one
      height specific (tape 1 or 2, depending on the animal's height) and two for
      general use (tapes 3 and 4). For horses up to 14.2 hh, weigh tape 1 provided the
      most accurate estimate of mean (sd) bodyweight (100.5 [6.2] per cent), and weigh
      tapes 3 and 4 were 112 (6.8) and 97-0 (6.1) per cent accurate, respectively. For
      horses more than 14.2 hh, weigh tape 2 provided the most accurate estimate of
      bodyweight (98.6 [18.4] per cent), with weigh tapes 3 and 4 being 102.6 (17.4)
      and 90.8 (15.2) per cent accurate, respectively.

PMID- 12046790
TI  - Seroprevalence of canine monocytic ehrlichiosis on Reunion.

PMID- 12046791
TI  - Parasites and their control in South American camelids in the United Kingdom.

PMID- 12046792
TI  - Surgical repair of intermandibular fistula with protrusion of the tongue in a
      buffalo.

PMID- 12046793
TI  - Centre for tropical veterinary medicine.

PMID- 12046794
TI  - Low blood urea levels in cattle.

PMID- 12046795
TI  - National movement restrictions and FMD.

PMID- 12046796
TI  - Embodied metaphor in women's narratives about their experiences with cancer.
AB  - Many scholars and medical professionals argue over the importance of metaphor in
      thinking about, and speaking of, cancer and other illnesses. Our study presents
      an analysis of the metaphors used by 6 women in their narratives of their
      experiences with cancer. We claim from our analyses that metaphorical talk about
      cancer reflects enduring metaphorical patterns of thought. Women used multiple,
      sometimes contradictory metaphors to conceptualize their complex cancer
      experiences. Many of their metaphors used to understand cancer are actually based
      on ordinary embodied experiences such that people still refer to the healthy body
      in trying to understand cancer even when their own bodies have been disrupted. We
      discuss the importance of our findings for understanding the relation between
      language and thought in regard to human illness.

PMID- 12046797
TI  - Smoke screen: an ethnographic study of a cigar shop's collective rationalization.
AB  - It is the purpose of this ethnographic study to explain why efforts from the
      medical establishment, the press, and friends and family are unsuccessful in
      persuading a group of men at a local cigar shop to stop smoking. I also seek to
      determine how these men create a linguistic defense shield that, ironically,
      protects them from the anxiety that such messages are designed to produce. I
      argue that the regulars at the shop collectively craft and share 6 prosmoking
      arguments that (a) rebuke the findings of the medical establishment, (b)
      anesthetize the regulars from the impact of antismoking messages, and (c) relieve
      cognitive dissonance and anxiety created by the act of smoking. I establish a
      theoretical foundation for the study, describe how the regulars craft and
      converge their collective narratives, and detail the 6 collectively created
      prosmoking narratives most frequently used by the regulars in countering
      antismoking messages.

PMID- 12046798
TI  - How do conflict and communication patterns between fathers and daughters
      contribute to or offset eating disorders?
AB  - As many as 22% of young women regularly engage in eating disordered behaviors.
      Research indicates eating disorders are a result of a complex set of factors,
      including family environment. This survey research with 210 undergraduate women
      at 2 universities tests the possibility that father-daughter communication and
      conflict resolution are related to eating disordered behaviors. Results indicate
      skilled conflict resolution and open communication between father and daughter
      may offset eating disorders. A lack of those skills or attempting to resolve
      conflict in ways that do not offer long-term resolution for both father and
      daughter can lead to increased eating disordered behaviors. Implications are
      discussed.

PMID- 12046799
TI  - Cancer patients' desires for communication of prognosis information.
AB  - A mail survey was sent to cancer patients to determine how often they want,
      request, and receive a qualitativeprognosis (i.e., will they die from the
      disease?) and a quantitative estimate (how long they will survive). The survey
      included measures of social and psychological characteristics that were
      hypothesized to be associated with their desire for and willingness to request
      prognosis information (N = 352). Major findings are as follows: (a) Whereas about
      80% of patients wanted a qualitative prognosis, only about one half wanted a
      quantitative one; (b) over 90% of those who wanted a qualitative prognosis were
      given one, but only about one half of those who wanted a quantitative prognosis
      were given one; and (c) about 15% ofthose who wanted a qualitative prognosis
      failed to ask for it, and over one third of those who wanted a quantitative
      prognosis failed to ask for it. Multivariate analyses indicate that the effects
      of education on wanting, asking for, and receiving prognosis information are
      slight, and the effects of sex are essentially nil. Older people were
      significantly less likely to request and to be given prognosis information. Those
      who had greater anxiety and who needed to avoid thinking about death wanted,
      requested, and received significantly less information. Fear had significant
      nonlinear effects on desire, request, and receipt of quantitative information.
      Those whose prognosis was worse were less likely to want, ask for, and receive
      quantitative information. Those least likely to want, request, and be given
      qualitative information were those who combined a bad prognosis with a need to
      avoid thinking about death.

PMID- 12046800
TI  - The death of Loving: maternal identity as moral constraint in a narrative
      testimonial advocating physician assisted suicide.
AB  - This article considers the narrative testimonial as a rhetorical form in the
      service of public judgment, with particular attention to the witness's
      credibility and communicative competence. The author argues that a narrator and
      witness, as a participant-observer of the events recounted, must generate a story
      that does not compromise her credibility as a moral agent within the text, and
      that the capacity to do so is largely a function of communicative competence.
      Carol Loving's recent book concerning her son's physician assisted suicide is
      critically assessed to illustrate the primary argument. The critique attempts to
      show that she neither creates a substantial argument for physician assisted
      suicide, nor does she warrant her role as a spokesperson for the issue because
      her narrative violates formative features of maternal identity. Loving's
      narrative also unintentionally reveals motivational clusters that conflict with
      and compromise the primary argument, thereby subverting the process of persuasive
      appeal. Whereas mothers are often mediators for their children in health matters
      ranging from colds, to psychiatric issues, to matters of death and dying, the
      failure of Carol Loving in this text, as well as its analysis, should be
      instructive and cautionary to health professionals who rely on maternal discourse
      in handling patients, as well as audiences who rely on narrative testimonials as
      content in their deliberation of public issues.

PMID- 12046801
TI  - A complementary strategy to reduce tractor overturn fatalities: sell more new
      tractors and retire the old ones.

PMID- 12046802
TI  - Cognitive-behavioral approaches to farm community safety education: a conceptual
      analysis.
AB  - For many years, farm health and safety education efforts have focused on the
      presentation of safety rules and guidelines. This method of instruction tends to
      ignore the contingencies that influence the actual behavior of farmers.
      Consequently, while most farmers understand the safety instruction messages they
      receive, they frequently continue to engage in risky behaviors. They do so even
      when they are aware of the injury consequences that can result from engaging in
      risky behaviors during farm work. Consequently, educational programs for the
      delivery of farm health and safety knowledge have been judged to be of
      questionable effectiveness. Yet, current political, social, and economic
      realities suggest that safety and health education will remain a favored
      methodology for the foreseeable future. These observations suggest that farm
      safety education efforts may need to be reconceptualized. This article examines
      the learning of safe and unsafe work practices from three historical learning
      theory perspectives: behaviorism, constructivism, and socioculturalism. The
      conceptual analysis is illustrated through case study examples. The analysis may
      provide insights into why transmission of knowledge by itself is not effective
      for replacing risky behaviors with safe work practices. It may also assist the
      design of farm health and safety education programs that impart knowledge, as
      well as change attitudes and behavior that support safe work practices.

PMID- 12046803
TI  - Coalitions: partnerships to promote agricultural health and safety.
AB  - Throughout the 1990s, a variety of partnerships and community-based organizations
      have been formed with the primary mission to promote agricultural safety and
      health. These groups are altruistic, creative, energetic, and provide critical
      perspectives for improving the safety and health of the agricultural workforce at
      the local, regional, and national levels. These coalitions have been created as a
      result of philanthropic support, public funding, grassroots interest, and
      personal experiences with agricultural injuries andfatalities. They are playing
      important roles in collaborating with researchers and in reaching the individual
      agricultural communities. They have been instrumental in conducting needs
      assessments and are critical to the development and implementation of successful
      surveillance programs and interventions. Outreach and dissemination of research
      findings and other safety and health information to target audiences are
      strengths of these diverse coalitions. This article will focus on primarily
      community-based coalitions, providing an overview of the development, foci,
      membership activities, and contributions or impact of these groups during the
      1990s and the challenges in maintaining and sustaining the coalitions. This
      information should be useful to those seeking to understand the activities of
      existing coalitions and identify potential partnerships for future activities.

PMID- 12046804
TI  - Public health concerns for neighbors of large-scale swine production operations.
AB  - This article provides a review and critical synthesis of research related to
      public health concerns for neighbors exposed to emissions from large-scale swine
      production operations. The rapid industrialization of pork production in the
      1990s produced a generation of confined animal feeding operations (CAFOs) of a
      size previously unseen in the U.S. Recent research and results from federally
      sponsored scientific symposia consistently indicate that neighbors of large-scale
      swine CAFOs can experience health problems at significantly higher rates than
      controlled comparison populations. Symptoms experienced by swine CAFO neighbors
      are generally oriented toward irritation of the respiratory tract and are
      consistent with the types of symptoms among interior confinement workers thathave
      been well documented in the occupational health literature. However, additional
      exposure assessment research is required to elucidate the relationship of
      reported symptoms among swine CAFO neighbors and CAFO emissions.

PMID- 12046805
TI  - Tractor risk abatement and control as a coherent strategy.
AB  - The agricultural tractor was the principal source of fatal injury on American
      farms for the latter part of the 20th century, and they maintain that distinction
      today. Much has been learned about the toll of these fatalities and how to
      prevent them over the last ten years, yet public policy has generally been
      unsuccessful in reducing this toll. A policy conference entitled Tractor Risk
      Abatement and Control convened in 1997 to develop recommendations to reduce this
      death toll. Several stakeholders at the conference agreed on 25 action items,
      which if implemented would reduce the number of tractor-related deaths by more
      than 2,000 by the year 2015. These recommendations relate to tractor overturns,
      runovers, and traffic collisions as well as youth operators. This article
      addresses the completeness of a strategy for preventing tractor-related injuries
      for each of these four areas based upon an evaluation model derived from the
      Theory of Planned Behavior and an antecedent model. The ultimate result of this
      model is to influence an individual's intention to act to prevent injury. The set
      of recommendations was found to provide a coherent strategy. In addition,
      implementing the strategy at an organizational level is discussed.

PMID- 12046806
TI  - Current health effects of agricultural work: respiratory disease, cancer,
      reproductive effects, musculoskeletal injuries, and pesticide-related illnesses.
AB  - Agriculture has experienced major bio-technological advances and economic and
      socio-cultural disruptions since the publication of "Agriculture at Risk" in
      1988. At that time, it was recognized that there were acute needs in the
      prevention of musculoskeletal syndromes and injuries, agricultural respiratory
      disease, noise-induced hearing loss, pesticide-related illnesses, and concerns
      regarding the excesses of cancers noted in epidemiological studies of farmers. In
      this article, we discuss the progress made in identification of new respiratory
      syndromes related to confined animal feeding operations, pesticide-related
      illnesses, cancers implicating agricultural exposures, and ergonomics in
      agriculture. The focus is on the current state of knowledge in these areas, the
      author's recommendations for further improvement in research techniques, and the
      potential application of this information to improve human health in production
      agriculture nationwide.

PMID- 12046808
TI  - Stories or statistics? Farmers' attitudes toward messages in an agricultural
      safety campaign.
AB  - Farming is the second most hazardous occupation in the U.S. The high mortality
      rate is due in large part to farm equipment hazards, particularly tractor
      overturns. Injuries and deaths associated with tractor overturns could be
      prevented with the use of a rollover protective structure (ROPS). In spite of the
      known dangers associated with overturn incidents, farmers are reluctant to
      retrofit ROPS on older tractors. Few agricultural safety campaigns target the
      issue of ROPS retrofits, and none have been evaluated systematically. This
      article reports a study that examines a set of messages that were central to the
      Community Partners for Healthy Farming project. This study indicates that
      narrative-based messages and messages incorporating fear appeals are more
      favorably evaluated by farmers than messages that simply inform farmers or
      messages that rely on statistics.

PMID- 12046807
TI  - Agricultural machinery injuries in Ontario, 1985-1996: a comparison of males and
      females.
AB  - Males and females on farms perform different types of work. This study
      investigated whether certain injuries experienced by women and men on farms also
      differed. Gender-based comparisons were made of fatal and hospitalized
      agricultural machinery injuries that took place in Ontario, Canada, between 1985
      and 1996. Data compiled by the Canadian Agricultural Injury Surveillance Program
      (CAISP) were used. Comparisons were based on 2,333 injury records and six
      descriptors: age group, time period, agricultural season in which the injury
      occurred, machinery involved, mechanism of injury, type of machinery, and
      admission category (where applicable). Distributions of injuries between males
      and females were statistically different by age group, agricultural production
      season, and mechanism of injury. These and other differences suggest that gender
      specific injury patterns exist. Future studies should examine thefactors
      contributing to these differences, including degree and duration of exposure to
      agricultural machinery.

PMID- 12046809
TI  - Tacrolimus: a review of its use for the management of dermatoses.
AB  - The newly developed immunomodulator tacrolimus (FK506) is the first of a new
      class of agents that have enormous potential to change the way that dermatoses
      are treated and managed. Tacrolimus has been found to be active in a topical
      formulation with the latter exerting its effects by acting on the signal
      transduction pathways inside T cells and inhibiting gene transcription. The
      result is decreased responsiveness of T cells to antigens. Percutaneous
      absorption of tacrolimus is higher in diseased skin as opposed to healthy skin
      and, therefore, the drug will be taken in at progressively lower quantities as
      lesions heal. There is limited systemic absorption of tacrolimus over the course
      of therapy. The most extensive experience with tacrolimus has been in treating
      atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to
      be effective in reducing the symptoms and severity of atopic dermatitis in adults
      and the paediatric population. Furthermore, there have been no significant toxic
      effects associated with topical therapy with tacrolimus. The most common
      complaint is that of local irritation after applying the ointment. This is
      generally transient and the patient is able to continue with therapy. The other
      dermatoses where tacrolimus has been used include contact dermatitis, psoriasis
      and pyoderma gangrenosum.

PMID- 12046810
TI  - Comparison of mastocytosis with onset in children and adults.
AB  - OBJECTIVE: To compare the incidence, symptomatology and course of mastocytosis
      with onset in childhood and in adults. DESIGN: Retrospective study of 101
      patients with mastocytosis who were referred from 1980 to 1998. PATIENTS: Medical
      records of 65 cases of mastocytosis with onset in childhood and 36 in adulthood
      were analysed. The clinical course was assessed in a subgroup consisting of 33
      subjects with childhood onset who were followed up until at least adolescence and
      12 subjects with adult onset who were followed up for at least 10 years. RESULTS:
      The onset of the disease occurred before the age of 2 years in 50% and between
      the ages of 2 and 15 years in 14% of cases (childhood onset). In 36% of patients
      onset occurred at the age of 16 years and older (adult onset). An incidence peak
      of 60% was noted in the first year of life. Mast cell-mediated symptoms were not
      experienced by 21 of 36 adult onset mastocytosis patients nor by 27 of 65
      childhood onset mastocytosis patients. Complete resolution was observed in five
      of 33 children. The majority of childhood onset cases (21 of 33) showed some
      improvement. Complete resolution was achieved in three of 12 adults. The majority
      of the remaining adults (eight of 12) showed no improvement. CONCLUSIONS: We
      confirm the incidence of onset of mastocytosis previously reported in the
      literature. We conclude that childhood onset mastocytosis is much less transitory
      than generally is assumed, although improvement occurs in the majority of cases.
      Symptomatology and clinical course of adult onset mastocytosis is less severe
      than suggested in the literature.

PMID- 12046811
TI  - Which steroids for the treatment of skin disorders on the face?

PMID- 12046812
TI  - Steroid dermatitis resembling rosacea: aetiopathogenesis and treatment.
AB  - BACKGROUND: Corticosteroids were first introduced for topical use in dermatology
      in 1951. Since then uncontrolled use (abuse) has caused many different reactions,
      often with manifestations resembling those of rosacea. OBJECTIVE: The prolonged
      use of local corticosteroids (usually 2-6 months) may lead to a clinical picture
      of severe dermatitis with erythema, papules and pustules that are classified
      according their localization to three types. The treatment of choice is
      tetracycline in combination with local application of neutral ointments.
      CONCLUSIONS: Trivial skin dermatoses, especially on the face, should not be
      treated with local corticosteroids.

PMID- 12046813
TI  - Treatment of recalcitrant psoriatic arthritis with anti-tumor necrosis factor
      alpha antibody.
AB  - Currently available treatments for psoriatic arthritis are either not completely
      effective or toxic in some patients. As tumour necrosis factor (TNF)-alpha is
      involved in both the joint and skin involvement in psoriatic arthritis, blockade
      of TNF-alpha seems a reliable way to treat patients with this disease. We report
      two patients with progressive recalcitrant psoriatic arthritis treated with low
      dose methotrexate (7.5 mg, once per week) in combination with intravenous
      chimeric monoclonal anti-TNF-alpha antibody (infliximab, 3 mg/kg body weight).
      Both showed a dramatic and rapid response in the reduction of pain, followed by
      improvement of laboratory and clinical signs of joint inflammation. Skin disease
      also responds after a short delay. The observation shows that infliximab is
      effective and well tolerated in patients with recalcitrant progressive psoriatic
      arthritis. Different kinetics of symptom release during treatment suggest a
      variable role for TNF-alpha in disease pathways of pain, joint inflammation and
      skin involvement.

PMID- 12046815
TI  - Keratin-9 gene mutation in a family with epidermolytic palmoplantar keratoderma.
AB  - BACKGROUND: Epidermolytic palmoplantar keratoderma is an autosomal dominant
      inherited disorder of keratinization. METHODS: We studied five members of a
      Jewish family with epidermolytic palmoplantar keratoderma. Genomic DNA was
      extracted from leucocytes, and exon 1 of the keratin 9 gene was amplified using
      polymerase chain reaction techniques. RESULTS: The mutation was found in exon 1
      of the keratin 9 gene in codon 160. CONCLUSIONS: Like most of the other families
      with clinical features of epidermolytic palmoplantar keratoderma the mutation is
      found in exon 1 of the keratin 9 gene.

PMID- 12046814
TI  - Potential human papillomavirus reactivation following topical corticosteroid
      therapy of genital lichen sclerosus and erosive lichen planus.
AB  - Using a highly sensitive polymerase chain reaction (PCR) technique, based on
      general GP5+/GP6+ PCR primers covering 34 different human papillomavirus (HPV)
      types, the presence of HPV DNA was studied in paraffin-embedded penile biopsies
      from 20 men treated topically with corticosteroids. Clobetasol propionate was
      applied for 2-16 (mean 7) weeks by 19 men (age 18-73; mean 40) with lichen
      sclerosus. High-risk HPV was detected prior to therapy in three patients (16%)
      who lacked clinical or histopathological signs of HPV infection. Following
      therapy high-risk HPV was detected in biopsies from four men (21%), of whom three
      also exhibited clinical and/or light microscopic signs of HPV infection. Low-risk
      HPV DNA was not detected in any of these samples. Four biopsies were collected
      during a 5-year period from a 51-year-old man who was treated repeatedly with
      topical mild-moderate potent corticosteroids at intervals of up to 10 weeks for
      penile erosive lichen planus, followed by nine clinical outbreaks of typical
      condylomas that consistently showed the presence of low-risk HPV DNA only. These
      observations indicate that long-lasting topical corticosteroid therapy
      occasionally may be associated with opportunistic reactivation of a latent high-
      and low-risk mucosotrophic HPV type infection. The importance of clinical follow
      up is underlined.

PMID- 12046816
TI  - Treatment of vitiligo by topical calcipotriol.
AB  - OBJECTIVE: Evaluation of the efficiency of topical calcipotriol monotherapy in
      vitiligo. MATERIALS AND METHODS: This was a prospective, right/left comparative,
      open study at the Dermatology Department at the University Hospital in Nice,
      France. Twenty-four patients with localized or generalized vitiligo with
      symmetrical lesions were included. The main outcome measure was the evaluation of
      the percentage of repigmentation in treated target lesions and untreated control
      lesions for each patient. RESULTS AND CONCLUSIONS: Topical calcipotriol in
      monotherapy is not an effective treatment of vitiligo.

PMID- 12046817
TI  - Tinea pedis in European marathon runners.
AB  - BACKGROUND: Epidemiological studies suggest that 15% of the population in
      industrial countries suffer from tinea pedis (athlete's foot) and that persons
      who do sports are a high-risk population. OBJECTIVE: To investigate the
      responsibility of dermatophytes in interdigital lesions of the feet in European
      marathon runners and to identify associated risk factors. SUBJECTS AND METHODS:
      Runners of the 14th Medoc Marathon (n = 147) were interviewed on risk factors for
      tinea pedis and underwent physical and mycological examinations. RESULTS:
      Interdigital lesions of the feet were found in 66 runners (45%). A dermatophyte
      was isolated in 45 runners (31%), 12 of whom were asymptomatic. Trichophyton
      interdigitale and T. rubrum accounted for 49% and 35.5%, respectively, of the
      cases of tinea pedis. Thirty-three (22%) of the 102 runners free of dermatophyte
      infection had lesions resembling those of tinea pedis. Increasing age and use of
      communal bathing facilities were predictive of T. rubrum culture. CONCLUSIONS:
      Marathon runners are at high risk for tinea pedis, but dermatophytes are
      responsible for only half of the foot lesions found in runners. The existence of
      asymptomatic carriers calls for prophylactic measures.

PMID- 12046818
TI  - Childhood discoid lupus erythematosus: report of five new cases and review of the
      literature.
AB  - Discoid lupus erythematosus (DLE) is an uncommon disease in childhood. In this
      paper we present five new cases of childhood DLE. Two of them are identical twin
      brothers, who developed similar lesions during an interval of 5 years. This is in
      favour of the hypothesis that both genetic factors and somatic mutations, due to
      environmental factors, are implicated in the pathogenesis. A review of the
      English language literature is also presented. In order to have better
      epidemiological data on this disease, all cases of childhood DLE, including those
      published in non-English literature and those not yet published, should be placed
      together and analysed.

PMID- 12046819
TI  - Successful treatment of postoperative pyoderma gangrenosum with cyclosporin.
AB  - Postoperative pyoderma gangrenosum (PPG), also known as postoperative progressive
      gangrene of Cullen, is a rare and rapidly evolving complication of surgical
      procedures. Since the first description by Cullen in 1924 (Surg Gynecol Obstet
      1924; 38: 579-582) various case reports have been published. Even in typical
      cases PPG is often misdiagnosed and therefore wrongly treated; the unknown
      aetiology makes treatment difficult. The therapies used for pyoderma gangrenosum
      include systemic corticosteroids, azathioprine, dapsone, mercaptopurine,
      sulphasalazine, sulphapyridine, thalidomide, cyclophosphamide, clofazimine,
      isotretinoin, immunoglobulins and cyclosporin. We report on two patients with PPG
      following breast surgery who were successfully treated with low-dose cyclosporin
      (2.5-5 mg/kg per day).

PMID- 12046820
TI  - A case of pemphigus vulgaris possibly triggered by quinolones.
AB  - Pemphigus vulgaris is an autoimmune blistering disorder in which both genetic and
      environmental factors, mainly drugs, are thought to play a part in its
      aetiopathogenesis. Although some drugs that contain thiol groups, such as D
      penicillamine and captopril, and non-thiol drugs, such as cephalosporin, have
      been reported to trigger or induce pemphigus, there are no previous reports
      regarding the influence of quinolones in triggering this disease. Here we present
      a case of pemphigus possibly triggered by quinolones.

PMID- 12046821
TI  - Dermatofibrosarcoma protuberans with onset in early childhood: a case report.
AB  - Dermatofibrosarcoma protuberans is a tumour that grows locally, infiltrating the
      subcutaneous tissue; it is uncommon in children. We report the case of a 27-year
      old man who had had such a lesion from the age of 3 years, and it had enlarged
      during his lifetime. A wide local excision with margins of 3.0 cm was performed,
      but the lesion was not entirely removed. This is a new report of infantile
      dermatofibrosarcoma protuberans, and this case reflects the need for Mohs
      micrographic surgery.

PMID- 12046822
TI  - Facial and periorbital cellulitis with orbital involvement.
AB  - Orbital cellulitis is a rare, serious and potentially fatal condition, usually
      associated with trauma to the eyelids, external ocular infection, upper
      respiratory tract infection and, especially, sinusitis. It is distinct from the
      more common periorbital cellulitis because it involves all contents of the orbit
      and may threaten both the vision and the life of the patient. It occurs with
      greater frequency in children. We report the case of a 34-year-old woman with
      severe facial and right periorbital cellulitis who rapidly developed orbital
      involvement, as shown by computed tomography. Apart from a bilateral
      retroauricular dermatitis, present for several years, the woman had been always
      healthy. Systemic antibiotics were started without delay and she recovered very
      well, with no ocular sequelae. This case illustrates that a subset of bacterial
      skin infections is becoming more aggressive and should be recognized and treated
      early.

PMID- 12046823
TI  - Superficial granulomatous pyoderma: an idiopathic granulomatous cutaneous
      ulceration.
AB  - A 70-year-old male with a superficial granulomatous ulcer is reported.
      Histopathological findings were the same as those described for superficial
      granulomatous pyoderma, a recognized variant of classic pyoderma gangrenosum. The
      differences between pyoderma gangrenosum and its variant superficial
      granulomatous pyoderma are highlighted.

PMID- 12046824
TI  - Supravenous hyperpigmentation, transverse leuconychia and transverse melanonychia
      after chemotherapy for Hodgkin's disease.
AB  - Pigmentary abberations of the skin, mucosa and epidermal appendages are common
      side-effects after systemic treatment with chemotherapeutic agents. These pigment
      changes appear in different patterns and are partly quite typical for the applied
      chemotherapeutic drug. The pathogenesis of the different skin pigmentations are
      not well known. The most often discussed causes are the stimulation of
      melanocytes, involvement of the tyrosinase enzyme system and thrombophlebitis
      with postinflammatory hyperpigmentation by the aggressive substances. Nail
      discolorations are mainly due to direct toxic effects and stimulation of the
      matrix melanocytes. We report a rare event of supravenous hyperpigmentation,
      transverse leuconychia and melanonychia after chemotherapy of a patient suffering
      from Hodgkin's disease.

PMID- 12046825
TI  - Primary cutaneous plasmacytosis in a child. Is this a new entity?
AB  - Plasma cell proliferations represent a heterogeneous spectrum of disorders. A 7
      year-old Caucasian female had suffered an asymptomatic eruption on the trunk for
      4 years. Physical examination revealed a plaque with scattered red-brown papules
      and nodules. Chemical analysis revealed normal proteinaemia. Histological
      examination of biopsy specimens showed dense perivascular and periadnexal
      infiltrate, consisting largely of plasma cells, in the superficial and deep
      dermis. Immunohistochemical study showed that many cells of the infiltrate were
      CD20 positive. The plasma cells expressed kappa and lambda light chains. The
      girl's status (age; absence of hypergammaglobulinaemia, lymphadenopathy and
      hepatosplenomegaly; presence of an infiltrate of mature polyclonal plasma cells
      restricted only to the skin) differed from those generally seen in diseases with
      plasma cell proliferation reported in the literature. This case seems unlike any
      other described up to the present time.

PMID- 12046826
TI  - Seborrhoeic keratosis or occult malignant neoplasm of the skin?
AB  - BACKGROUND: Seborrhoeic keratosis is generally considered to be a benign lesion
      of the skin. OBSERVATION: We present the case of a 68-year-old male who presented
      with clinically typical seborrhoeic keratosis that later histological examination
      showed partially covered an occult basal cell carcinoma. OBJECTIVE: To have an
      indication of what percentage of clinically apparent seborrhoeic keratoses may be
      associated with some form of histologically proven skin malignancy. METHODS: We
      carried out a retrospective analysis of approximately 23,000 histopathological
      examinations done on specimens from dermatological lesions. RESULTS: Fifty-nine
      (11.9%) clinically apparent seborrhoeic keratoses were later histologically
      diagnosed as basal cell carcinomas, 17 (3.4%) as squamous cell carcinomas, and
      five (1.01%) as malignant melanomas. CONCLUSIONS: Although the association of
      seborrhoeic keratosis and skin malignancy appears to be relatively uncommon, the
      possibility of such an association cannot be ruled out.

PMID- 12046827
TI  - Axillary hyperhidrosis treated with botulinum toxin A exotoxin.

PMID- 12046828
TI  - Dermatomyositis without muscle weakness associated with transitional cell
      carcinoma of the bladder.

PMID- 12046829
TI  - Lichen planus actinicus treated with acitretin and topical corticosteroids.

PMID- 12046830
TI  - Perioral dermatitis successfully treated with topical adapalene.

PMID- 12046831
TI  - Poor prognosis of acute myeloid leukaemia associated with leukaemia cutis.

PMID- 12046832
TI  - Azelaic acid (20%) cream in the treatment of acne vulgaris.

PMID- 12046833
TI  - Neurofibromatosis type I and Arnold-Chiari malformation.

PMID- 12046834
TI  - Treatment with pentoxifylline in Behcet's disease.

PMID- 12046835
TI  - Toxic epidermal necrolysis due to cotrimoxazole.

PMID- 12046836
TI  - Lichen sclerosus et atrophicus of the scalp: satisfactory response to acitretin.

PMID- 12046837
TI  - Palmar telangiectases and lung carcinoma: a possible association?

PMID- 12046838
TI  - Topical immunotherapy with squaric acid dibutylester: unusual hair pigmentary
      changes in two cases of alopecia areata.

PMID- 12046839
TI  - Red fingers syndrome associated with hepatitis C virus.

PMID- 12046840
TI  - UEMS Section of Dermatology and Venereology, European Board of Dermatology and
      Venereology, Report meetings Section and Board, 19 May 2001.

PMID- 12046841
TI  - Superficial granulomatous pyoderma: who are you?

PMID- 12046843
TI  - Stem cells: a minireview.
AB  - The identification of adult-derived stem cells which maintain plasticity
      throughout the course of a lifetime, has transformed the field of stem cell
      biology. Bone marrow derived hematopoietic stem cells (HSC) are the most well
      characterized population of these multipotential cells. First identified for
      their ability to reconstitute blood lineages and rescue lethally irradiated
      hosts, these cells have also been shown to differentiate and integrate into
      skeletal muscle, cardiac myocytes, vascular endothelium, liver, and brain tissue.
      Various populations of HSC are being studied, exploiting cell surface marker
      expression, such as Sca-1, c-kit, CD34, and lin; as well as the abilityto efflux
      the vital dye Hoecsht 33342. Detection of engrafted donor derived cells into
      various tissue types in vivo is a laborious process and may involve detection of
      beta-galactosidase via colorimetric reaction or antibody labeling or green
      fluorescent protein (GFP) via fluorescence microscopy, as well as in situ
      hybridization to detect the Y-chromosome. Using these techniques, the search has
      begun for tissue specific stem cells capable of host tissue regeneration, self
      renewal, and transdifferentiation. Caution is urged when interpreting these types
      of experiments because although they are stimulating, limitations of the
      technologies may provide misleading results.

PMID- 12046844
TI  - Regulatory issues in cellular therapies.
AB  - Cellular and gene therapies offer considerable promise as new treatment
      modalities. The Food and Drug Administration has been developing strategies to
      regulate these rapidly evolving fields in a manner that sustains progress and
      also ensures minimization of potential risks. The death of a patient on a gene
      therapy study highlighted a number of potential problems that have galvanized the
      agency to examine their strategy and to review current regulations for gene
      therapy. Meanwhile, a unified regulatory approach is emerging for cell-based
      therapies. This stratifies the level of regulation based upon the potential risk
      to the donor of the cells and the recipient. In this article the history and
      status of regulation of cellular therapy is briefly reviewed.

PMID- 12046842
TI  - Borrelia burgdorferi: a protagonist in Lyme disease, a bystander in morphoea?

PMID- 12046845
TI  - Stem cells and the philosopher's stone.
AB  - Stem cell biology is now one of the most exciting and rapidly advancing areas of
      scientific endeavor. Promises of cures of a wide variety of diseases by specific
      replacement of damaged or malfunctional tissues by use of totipotent or
      multipotent stem cells is on the horizon in clinical practice. Stem cells derived
      from the embryo and from adult tissues have been shown to have extensive
      potentials for self-renewal and differentiation. In addition, the plasticities of
      phenotype exhibited in vivo by some of these cell populations challenge the
      doctrine of irreversibility of cell commitment after particular developmental
      stages. This brief review considers certain aspects of these recent findings of
      the many unexpected potentials of stem cells to differentiate into alternative
      processes, and their potential value for use in tissue reconstruction procedures
      are prominent areas that require further study. Rigorous investigation of these
      topics will lead to realistic approaches in the future for stem cell therapy in a
      variety of human diseases and other clinical problems.

PMID- 12046846
TI  - Adult bone marrow stem cells for cell and gene therapies: implications for
      greater use.
AB  - There is excitement generated almost daily about the possible uses of stem cells
      to treat human disease. Much of the interest of late is generated by embryonic
      stem cells (ESCs). As exciting as ESCs may be, they are quite controversial for
      moral reasons, given their source. They are also scientifically controversial
      since they are much less well understood than the original, long-standing, and
      clinically successful hematopoietic stem cell (HSC). HSCs have the distinct
      advantage of being reasonably well characterized and have been proven in the
      clinic. They can be isolated by simple procedures directly from the bone marrow
      or from peripheral blood after being stimulated (mobilized). They can then be
      manipulated and delivered to a patient, often producing a cure. Their biology
      provides the paradigm by which all other stem cells are judged, and they have
      little in the way of moral controversy surrounding them given they are isolated
      from adults who have consented to the procedure. Another putative stem cell has
      gained momentum in the last few years; the mesenchymal stem cell (MSC). MSCs
      appear to have much in common with HSCs. They were originally characterized from
      bone marrow, are capable of differentiating along multiple lineages and, at least
      in vitro, have significant expansion capability. Unlike HSCs, they have not yet
      been definitively shown to function as stem cells, despite their ability to
      differentiate into various mesenchymal cell types under the right culture
      conditions. Still, there is mounting evidence these cells may be useful, if not
      as true stem cells then at least as vehicles for emerging cell and gene
      therapies, especially in the field of tissue engineering. While this is an
      important endpoint, it is more important to thoroughly understand stem cell
      biology. That understanding can then be applied toward the ultimate goal of using
      these cells not just for various forms of therapy, but rather as a tool to
      discover the mechanisms and means to bring about directed repair and regeneration
      of damaged or diseased tissues and organs. The excitement of HSCs and MSCs has
      been muted somewhat by the excitement surrounding ESCs, primarily due to the fact
      HSCs and MSCs are viewed as limited to specific cell types while ESCs could
      potentially be applied to any cell type. Recent information indicates HSCs, MSCs,
      and other cells in general may have more universal differentiation abilities than
      previously thought.

PMID- 12046847
TI  - Cytokine and chemokine networks influencing stem cell proliferation,
      differentiation, and marrow homing.
AB  - The hematopoietic stem cell (HSC) is an attractive target for gene therapy of
      genetic diseases of the immune and hematopoietic system, and for drug-resistance
      strategies in which genes conferring resistance to a variety of chemotherapeutic
      agents can be transduced. Stem cells are relatively easy to obtain; e.g., by
      marrow aspiration or G-CSF mobilization into the peripheral blood, and can be
      enriched e.g., by the use of anti-CD34 + monoclonal antibody. For conventional
      retroviral transduction, normally quiescent HSC must be activated into the cell
      cycle by priming with appropriate cytokines, and it has been critical to identify
      cytokine combinations that preserve the self-renewal capacity of long-term
      repopulating HSC. It has become apparent that strategies designed to optimize HSC
      cycling and proviral integration can compromise the capacity of transduced HSC to
      compete in vivo against endogenous HSC or HSC that have not been activated into
      cell cycle. Lentiviral vectors can integrate genes into non-cycling cells but
      there is an increased efficiency of transduction if Go HSC are activated into G1
      phase of the cell cycle. This reduced efficiency of long-term engraftment of ex
      vivo cultured HSC may be due to impaired self-renewal capacity or reduced marrow
      homing efficiency. The latter may be attributed to down modulation of chemokine
      receptors necessary for chemotactic homing to the marrow. Alternatively, or in
      addition, there may be down modulation of (1) HSC adhesion molecules necessary
      for endothelial adhesion and egress from the circulation: (2) metalloproteinases
      secreted by HSC that facilitate their migration through extracellular matrix and
      promote release of critical soluble regulatory factors in the marrow
      microenvironment. A more controversial view is that cell death pathways, for
      example those involving FasR (CD95) may be activated in cycling HSC, resulting in
      their selective destruction upon transplantation and localization to sites rich
      in Fas ligand such as the liver.

PMID- 12046849
TI  - Post-transduction events in retrovirus-mediated gene therapy involving
      hematopoietic stem cells: beyond efficiency issues.
AB  - Numerous incremental technological improvements have occurred recently in the
      application of therapeutic retrovirus-mediated gene transfer into hematopoietic
      stem cells (HSCs). Improved transduction efficiencies are now reaching levels
      that may correct some inherited or acquired disorders. Novel retroviral vector
      systems likewise offer the possibility for an expanded portfolio of treatment
      approaches. Most importantly, however, investigators are now also focusing
      efforts on post-transduction events to fully impact correction. Here we describe
      recent advances in the field, with a special emphasis on the role of post
      transduction processes, for correction of disorders or treatments that involve
      HSCs or their progeny.

PMID- 12046848
TI  - Obstacles to human hematopoietic stem cell transduction by recombinant adeno
      associated virus 2 vectors.
AB  - Recombinant adeno-associated virus 2 (AAV) vectors have proven to be a
      potentially useful alternative to the more commonly used retroviral and
      adenoviral vectors for gene therapy in humans. Their safety and efficacy in Phase
      I clinical trials for gene therapy of cystic fibrosis and hemophilia B have been
      well documented, and their remarkable versatility and efficacy in a wide variety
      of pre-clinical models of human diseases have catapulted these vectors to the
      forefront. AAV vectors have been shown to be particularly well suited for
      transduction of brain and muscle cells. However, controversies exist with regard
      to their utility as a vector for gene transfer into human hematopoietic stem
      cells. On the one hand, some investigators have concluded that AAV vectors do not
      transduce hematopoietic stem cells at all, and others have reported that stem
      cell transduction requires enormously high vector-to-cell ratios. On the other
      hand, some investigators have reported high-efficiency transduction of human
      hematopoietic stem cells at low vector-to cell ratios. This article will provide
      a historical perspective as well as attempt to elaborate the reasons behind these
      controversies which have become clearer by studies focused on understanding, at
      the molecular level, the fundamental aspects of the life cycle of recombinant AAV
      vectors.

PMID- 12046850
TI  - Hematopoietic stem cell gene therapy for inherited bone marrow disorders: past
      accomplishments and continued challenges.
AB  - From the time that the genes encoding the defective proteins were cloned for a
      number of inherited diseases, it became a goal to correct those conditions by
      restoring the normal gene and thereby, its product. For the inherited disorders
      affecting the blood and its progenitor cells, the hematopoietic stem cells were
      the ideal target cells for gene transfer, because the normal gene would then be
      transferred to all of the progeny cells, theoretically for the lifetime of the
      recipient. However, the tasks of isolating the hematopoietic stem cells,
      introducing the new genes in such a manner as to preserve engraftment of the
      manipulated cells, and achieving long-term gene expression, have not been
      straightforward in the clinical trial setting, although there has been moderate
      success for cells in vitro, and in murine studies. With the report of clinical
      efficacy of gene transfer in children with X-linked severe combined
      immunodeficiency disease, the dream of clinical gene transfer to hematopoietic
      cells has become a reality. But there are still significant impediments remaining
      for a number of diseases. The innovations of introduction of synthetic receptors
      that confer growth advantage, the use of lentiviral vectors with increased stem
      cell transduction efficiency, and the addition of modified promoter/enhancer
      sequences to augment and preserve gene expression may bring wider success to gene
      therapy clinical trials for bone marrow disorders in the near future.

PMID- 12046852
TI  - Building a consensus regarding the nature and origin of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are believed to be the common precursors to
      differentiated cell lineages found in bone and bone marrow, including adipocytes,
      chondrocytes, osteoblasts, and hematopoiesis-supporting stroma. Apart from this
      fact, most aspects of MSC biology, including their ontogeny, anatomical location
      in marrow, and in vivo functions remain vague. Attempts to clarify these issues
      have produced confounding results, principally due to the fact that many
      researchers employ different methods to culture MSCs, assess their
      differentiation potential, and evaluate their capacity for self-renewal.
      Accordingly, the current status of the field appears fragmentary with no clear
      consensus on how to define the cells. In describing past and present
      contributions to the field of MSC research, I will demonstrate that the apparent
      incongruity of the literature is misleading, and that an unbiased interpretation
      reveals a fairly cohesive picture of MSC biology.

PMID- 12046851
TI  - Molecular basis of co-targeting prostate tumor and stroma.
AB  - Prostate cancer is one of the leading causes of cancer death in Northern American
      men. The lethal phenotypes of human prostate cancer are characterized by
      progression to androgen-independence (Al) and a propensity to form osseous
      metastases. In approximately 80% of cases, prostate cancer colonizes bone and
      elicits a characteristic osteoblastic reaction. The bone metastases are initially
      sensitive to androgen deprivation treatments, but with time the cancer will
      eventually progress into an Al stage for which there is currently no effective
      treatment. Once initial hormonal therapy has failed, median survival of prostate
      cancer patients with bone metastases is less than 1 year (Tu et al. [2001] Lancet
      357:336-341). Novel therapeutic and preventive strategies are needed to decrease
      morbidity and mortality of this disease.

PMID- 12046853
TI  - Mesenchymal stem cells: will they have a role in the clinic?
AB  - In addition to hematopoietic stem cells (HSC), human post natal bone marrow
      contains another stem cell capable of giving rise to multiple mesenchymal cell
      lineages. Termed mesenchymal stem cells (MSCs) based on their capacity for multi
      lineage differentiation, these cells can easily be obtained following a simple
      bone marrow aspiration procedure and subsequently expanded in culture through as
      many as 50 population doublings. This extensive capacity for expansion in vitro
      at clinical scale has recently facilitated the development of clinical trials
      designed to assess the safety, feasibility, and efficacy of transplanting MSC for
      a variety of pathological conditions. This review focuses on the background and
      rationale for performing clinical studies of MSC transplantation and will discuss
      the potential role that MSC may play in the correction or modification of human
      diseases.

PMID- 12046854
TI  - Recent advances in and therapeutic potential of muscle-derived stem cells.
AB  - Over the past few years, issues related to the commitment and potential of
      reservoir precursor cells that reside in most tissues have been revisited. Many
      reports have documented either plasticity or de-differentiation of a number of
      precursor cells isolated from several tissues, including bone marrow, brain, and
      skeletal muscle. These findings have challenged the dogma that mononuclear cells
      derived from adult, post-mitotic tissues can differentiate and contribute only to
      the tissue from which they originate. Thus, much current research in stem cells
      is testing the therapeutic potential of these cells to deliver normal genes and
      their encoded proteins into damaged or injured tissues. This review will focus on
      muscle-derived precursor cells and their apparently heterogeneous nature and
      summarize some of the most recent findings and hypotheses on their
      characterization and practical use.

PMID- 12046855
TI  - Interleukin 17: an example for gene therapy as a tool to study cytokine mediated
      regulation of hematopoiesis.
AB  - Interleukin 17 (IL-17) is an essential proinflammatory T-cell derived cytokine
      with various biological actions. IL-17 was found to have a pivotal role in
      microbial host defense by interconnecting lymphoid and myeloid host defense. It
      also acts as a stimulatory hematopoietic cytokine by expanding myeloid
      progenitors and initiating proliferation of mature neutrophils. This article
      summarizes results to date on IL-17 research and discusses gene therapy based
      strategies that were employed to determine its biological functions and
      significance. A comprehensive working model for IL-17 is introduced.

PMID- 12046856
TI  - Stem cell plasticity and blood and marrow transplantation: a clinical strategy.
AB  - The newly described phenomenon of stem cell plasticity raises interesting
      biological questions and offers exciting opportunities in clinical application.
      This review uses the well-established practice of blood and marrow
      transplantation as a paradigm to explore the clinical consequences of this
      finding. Recently proposed non-myeloablative conditioning regimens have shown
      that mixed donor-host hematolymphoid chimerism can be established with relatively
      low toxicity in both animal studies and human trials. Hematopoietic growth factor
      treatment of transplanted patients can mobilize a large number of donor stem
      cells to migrate from marrow to non-hematopoietic organs. We propose that these
      advances, in conjunction with the developmental plasticity of stem cells, can
      constitute components of a clinical strategy to use blood and marrow
      transplantation as a platform to treat systemic diseases involving non
      hematopoietic tissues.

PMID- 12046857
TI  - Comparison of outcome measures during treatment with the proprietary
      Harpagophytum extract doloteffin in patients with pain in the lower back, knee or
      hip.
AB  - Besides checking estimates of effectiveness and safety of using the proprietary
      Harpagophytum extract Doloteffin, this postmarketing surveillance compared
      various disease-specific* and generic** measures of effect. We enrolled 250
      patients suffering from nonspecific low back pain (Back group: n = 104) or
      osteoarthritic pain in the knee (Knee group: n = 85) or hip (Hip group: n = 61).
      They took an 8-week course of Doloteffin at a dose providing 60 mg harpagoside
      per day. The measures of effect on pain and disability included the percentage
      changes from baseline of established instruments (Arhus low back pain index*,
      WOMAC index*, German version of the HAQ**) and unvalidated measures (total pain
      index*, three score index*, the patient's global assessment** of the
      effectiveness of treatment). Patients also received a diary for the daily
      recording of their pain and any additional treatments for it. The three groups
      differed in age, weight and characteristics of initial pain. 227 patients
      completed the study. Multivariate analysis confirmed that several dimensions of
      effect were recorded by the several outcome measures but, in all groups, both the
      generic and disease-specific outcome measures improved by week 4 and further by
      8. In multivariable analysis, the improvement tended to be more when the initial
      pain and disability score was more: older patients tended to improve less than
      younger, the hip group tended to improve convincingly more than the back group,
      whereas the improvement in the knee group was less readily differentiated from
      that in the back group. The subgroup of Back patients who required NSAIDs during
      the 8 weeks used significantly more per patient than patients in the other two
      groups, but that requirement also declined more with time. About 10% of the
      patients suffered from minor adverse events that could possibly have been
      attributable to Doloteffin. Between 50% and 70% of the patients benefitted from
      Doloteffin with few adverse effects. Thus, Doloteffin is well worth considering
      for osteoarthritic knee and hip pain and nonspecific low back pain.

PMID- 12046858
TI  - Effect of Seihai-to, a Kampo medicine, in relapsing aspiration pneumonia--an open
      label pilot study.
AB  - Two published case reports described palliation of disease after Seihai-to
      therapy for refractory aspiration pneumonia caused by recurrent laryngeal nerve
      paralysis and cerebrovascular disease. We undertook an open-label trial in
      patients with relapsing aspiration pneumonia. Fifteen patients with relapsing
      aspiration pneumonia were randomly divided into conventional therapy group (n =
      8) or Seihai-to group (n = 7). In Seihai-to group, patients were treated with
      Seihai-to in addition to conventional therapy (Western medicines). Frequency of
      feverish days and antibiotics-use, CRP value and chest CT or X-ray findings were
      compared between the two groups during the study period of 16 weeks. In the
      Seihai-to group, the latency of swallowing reflex was measured in 6 patients
      before and after administration of Seihai-to. The mean values of fever index, CRP
      value and antibiotics-use in the Seihai-to group were decreased significantly,
      compared with those of the conventional therapy group. However, the latency of
      the swallowing reflex after 4 weeks of treatment was not significantly changed (p
      = 0.249), compared with the latency before administration of Seihai-to. No
      adverse reaction was observed in either group. Seihai-to was effective in
      reducing relapse of aspiration pneumonia in this small group. Seihai-to might not
      improve the swallowing reflex, but might instead improve a defense mechanism or
      excessive inflammation caused by pneumonia in the lower airway. Further
      evaluation of Seihai-to therapy for patients with aspiration pneumonia in a
      larger population is warranted.

PMID- 12046859
TI  - Studies on the psychopharmacological activities of Rumex nepalensis Spreng. root
      extract in rats and mice.
AB  - The methanol extract of Rumex nepalensis Spreng. (Family - Polygonaceae) was
      assessed for different psychopharmacological activities in rats and mice by
      evaluation of general behaviour, exploratory behaviour, muscle relaxant activity
      and phenobarbitone sodium-induced sleeping time. The extract at doses 200 mg/kg
      and above exhibited a reduction in spontaneous activity (general behavioural
      profile), a decrease in exploratory behavioural pattern in the Y-maze and Head
      dip tests, a reduction in muscle relaxant activity in rotarod, 30 degrees
      inclined screen and traction tests, and also potentiated phenobarbitone sodium
      induced sleeping time.

PMID- 12046860
TI  - Antidepressant activity of standardized extract of Bacopa monniera in
      experimental models of depression in rats.
AB  - Bacopa monniera Wettst. (syn. Herpestis monniera L.; Scrophulariaceae) is a
      commonly used Ayurvedic drug for mental disorders. The standardized extract was
      reported earlier to have significant anti-oxidant effect, anxiolytic activity and
      improve memory retention in Alzheimer's disease. Presently, the standardized
      methanolic extract of Bacopa monniera (bacoside A - 38.0+/-0.9) was investigated
      for potential antidepressant activity in rodent models of depression. The effect
      was compared with the standard antidepressant drug imipramine (15 mg/kg, ip). The
      extract when given in the dose of 20 and 40 mg/kg, orally once daily for 5 days
      was found to have significant antidepressant activity in forced swim and learned
      helplessness models of depression and was comparable to that of imipramine.

PMID- 12046861
TI  - Anticonvulsant activity of the leaf essential oil of Laurus nobilis against
      pentylenetetrazole- and maximal electroshock-induced seizures.
AB  - The leaf essential oil of Laurus nobilis Linn., Lauraceae, which has been used as
      an antiepileptic remedy in Iranian traditional medicine, was evaluated for
      anticonvulsant activity against experimental seizures. The essential oil
      protected mice against tonic convulsions induced by maximal electroshock and
      especially by pentylenetetrazole. Components responsible for this effect may be
      methyleugenol, eugenol and pinene present in the essential oil. At anticonvulsant
      doses, the essential oil produced sedation and motor impairment. This effect
      seems to be related in part to cineol, eugenol and methyleugenol. Although the
      essential oil had an acceptable acute toxicity, further studies are required
      before any absolute conclusions can be drawn.

PMID- 12046862
TI  - Anticonvulsant activity of aqueous extract of Leonotis leonurus.
AB  - Water extract of Leonotis leonurus was tested for anticonvulsant activity against
      seizures produced in mice by pentylenetetrazole, picrotoxin, bicuculline and N
      methyl-DL-aspartic acid (intraperitoneal injections). L. leonurus extract in the
      doses of 200 and 400 mg/kg respectively protected 37.5% and 50% of animals used
      and significantly (p < 0.05; Student's t-test) delayed pentylenetetrazole (90
      mg/kg)-induced tonic seizures. Similarly, the same doses of L. leonurus extract
      significantly (p < 0.05; Student's t-test) delayed the onset of tonic seizures
      produced by picrotoxin (8 mg/kg) and N-methyl-DL-aspartic acid (400 mg/kg).
      However, all the doses of aqueous extract of L leonurus used did not alter the
      seizures induced by bicuculline (20 mg/kg) to any significant extent. The data
      suggest that the extract of L. leonurus has anticonvulsant activity and may
      probably be acting through non-specific mechanisms, since it affects both
      gabaergic and glutaminergic systems. High performance liquid chromatography
      (HPLC) and phytochemical tests carried out respectively show a spectrum profile,
      characteristic of L. leonurus and the presence of alkaloids, saponins and tannins
      in the extract.

PMID- 12046863
TI  - Piperine modulates permeability characteristics of intestine by inducing
      alterations in membrane dynamics: influence on brush border membrane fluidity,
      ultrastructure and enzyme kinetics.
AB  - Piperine (1-Piperoyl piperidine) is a major alkaloid of Piper nigrum Linn. and
      Piper longum Linn. It is shown to possess bioavailability-enhancing activity with
      various structurally and therapeutically diverse drugs. The mechanism of
      enhancing the bioavailability, is, however, not understood. We hypothesize that
      piperine's bioavailability-enhancing property may be attributed to increased
      absorption, which may be due to alteration in membrane lipid dynamics and change
      in the conformation of enzymes in the intestine. Results of membrane fluidity
      studies using an apolar fluorescent probe, pyrene (which measures the fluid
      properties of hydrocarbon core), showed an increase in intestinal brush border
      membrane (BBM) fluidity. Piperine also stimulated Leucine amino peptidase and
      Glycyl-glycine dipeptidase activity, due to the alteration in enzyme kinetics.
      This suggests that piperine could modulate the membrane dynamics due to its
      apolar nature by interacting with surrounding lipids and hydrophobic portions in
      the protein vicinity, which may decrease the tendency of membrane lipids to act
      as stearic constrains to enzyme proteins and thus modify enzyme conformation.
      Ultra structural studies with piperine showed an increase in microvilli length
      with a prominent increase in free ribosomes and ribosomes on the endoplasmic
      reticulum in enterocytes, suggesting that synthesis or turnover of cytoskeletal
      components or membrane proteins may be involved in the observed effect. In
      conclusion, it is suggested that piperine may be inducing alterations in membrane
      dynamics and permeation characteristics, along with induction in the synthesis of
      proteins associated with cytoskeletal function, resulting in an increase in the
      small intestine absorptive surface, thus assisting efficient permeation through
      the epithelial barrier.

PMID- 12046864
TI  - Protective effect of green tea against lipid peroxidation in the rat liver, blood
      serum and the brain.
AB  - This paper reports data on the effect of green tea on the lipid peroxidation
      products formation and parameters of antioxidative system of the liver, blood
      serum and central nervous tissue of healthy young rats drinking green tea for
      five weeks. The rats were permitted free access to solubilized extract of green
      tea. Bioactive ingredients of green tea extract caused in the liver an increase
      in the activity of glutathione peroxidase and glutathione reductase and in the
      content of reduced glutathione as well as marked decrease in lipid hydroperoxides
      (LOOH), 4-hydroksynonenal (4-HNE) and malondialdehyde (MDA). The concentration of
      vitamin A increased by about 40%. Minor changes in the measured parameters were
      observed in the blood serum. GSH content increased slightly, whereas the index of
      the total antioxidant status increased significantly. In contrast, the lipid
      peroxidation products, particularly MDA was significantly diminished. In the
      central nervous tissue the activity of superoxide dismutase and glutathione
      peroxidase decreased while the activity od glutathione reductase and catalase
      increased after drinking green tea. Moreover the level of LOOH, 4-HNE and MDA
      significantly decreased. The use of green tea extract appeared to be beneficial
      to rats in reducing lipid peroxidation products. These results support and
      substantiate traditional consumption of green tea as protection against lipid
      peroxidation in the liver, blood serum, and central nervous tissue.

PMID- 12046865
TI  - Free radical scavenging action of the medicinal herb Limonium wrightii from the
      Okinawa islands.
AB  - Free radical scavenging action of Limonium wrightii O. kunthe was examined in
      vitro and in vivo by using electron spin resonance spectrometer and
      chemiluminescence analyzer. A water extract of L. wrightii showed a strong
      scavenging action for the 1,1-diphenyl-2-picrylhydrazyl, or superoxide anion and
      moderate for hydroxyl radical. The extract also depressed production of reactive
      oxygen species from polymorphonuclear leukocytes stimulated by phorbor-12
      mysistate acetate and inhibited lipid peroxidation in rat liver microsomes. When
      the extract was given intraperitoneally to mice prior to carbon tetrachloride
      (CCl4) treatment, CCl4-induced liver toxicity, as seen by an elevation of serum
      aspartate aminotransferase and alanine aminotransferase activities, was
      significantly reduced. Gallic acid was identified as the active component of L.
      wrightii with a strong free radical scavenging action. Our results demonstrate
      the free radical scavenging action of L. wrightii and that gallic acid
      contributes to these actions.

PMID- 12046866
TI  - The anti-inflammatory and analgesic effects of a crude extract of Petiveria
      alliacea L. (Phytolaccaceae).
AB  - Petiveria alliacea L (Phytolaccaceae) is a perennial bush plant that grows widely
      in Brazil. The roots and leaves of P. alliacea have been used in folk medicine
      for their antispasmodic, sedative, diuretic and antihelminthic actions. We
      recently described the anti-inflammatory properties of P. alliacea administered
      topically and orally in different animal models. In the present study, we
      investigated the anti-inflammatory activity of a crude lyophilized extract of P.
      alliacea roots administered to rats with pleurisy. The oral administration of P.
      alliacea root extract did not significantly reduce the total number of leukocytes
      at the doses tested. By contrast, the highest dose of extract tested (43.9 mg/kg
      body wt.) significantly reduced the number of migrating neutrophils, mononuclear
      cells and eosinophils; the dose of 31.4 mg/kg body wt. also reduced mononuclear
      cell migration. The P. alliacea root extract also showed a significant analgesic
      effect in the experimental model used. The results of this study provide a basis
      for the use of P. alliacea extracts in popular folk medicine, but further studies
      are necessary to elucidate the mechanism of its anti-inflammatory and analgesic
      actions.

PMID- 12046867
TI  - Bioactivity of alkamides isolated from Echinacea purpurea (L.) Moench.
AB  - Alkamides from the roots of Echinacea purpurea (L.) Moench were examined for anti
      inflammatory activity in an in vitro model system. Cyclooxygenase-I (COX-I) and
      cyclooxygenase-II (COX-II) inhibitory activities were assessed at pH 7 for
      alkamides isolated from E. purpurea roots to compare inhibitory activities
      between the two cyclooxygenase isozymes. At 100 microg/ml, several E. purpurea
      alkamides inhibited COX-I and COX-II enzymes in the range of 36-60% and 15-46%,
      respectively, as compared to controls. Mosquitocidal activity was assessed at 100
      and 10 microg/ml, with 100% mortality against Aedes aegyptii L. larvae noted for
      several E. purpurea alkamides at 100 microg/ml.

PMID- 12046869
TI  - Formulation of an effective mosquito-repellent topical product from lemongrass
      oil.
AB  - Ointment and cream formulations of lemongrass oil in different classes of base
      and the oil in liquid paraffin solution have been evaluated for mosquito
      repellency in a topical application. Mosquito repellency was tested by
      determining the bite-deterrence of product samples applied on an experimental
      bird's skin against a 2-day starved culture of Aedes aegypti L. mosquitoes. The
      1%v/v solution and 15%v/w cream and ointment preparations of the oil exhibited >
      or =50% repellency lasting 2-3 h, which may be attributed to citral, a major oil
      constituent. This activity was comparable to that of a commercial mosquito
      repellent. Base properties of the lemongrass oil formulations influenced their
      effectiveness. The oil demonstrated efficacy from the different bases in the
      order of hydrophilic base > emulsion base > oleaginous base.

PMID- 12046868
TI  - Ginseng berry reduces blood glucose and body weight in db/db mice.
AB  - In this study, we observed anti-diabetic and anti-obesity effects of Panax
      ginseng berry in adult C57BL/Ks db/db mice and their lean littermates. Animals
      received daily intraperitoneal injections of Panax ginseng berry extract at 150
      mg/kg body wt. for 12 consecutive days. On Day 5, the extract-treated db/db mice
      had significantly lower fasting blood glucose levels as compared to vehicle
      treated mice (180.5+/-10.2 mg/dl vs. 226.0+/-15.3 mg/dl, P < 0.01). On day 12,
      the extract-treated db/db mice were normoglycemic (134.3+/-7.3 mg/dl) as compared
      to vehicle-treated mice (254.8+/-24.1 mg/dl; P < 0.01). Fasting blood glucose
      levels of lean mice did not decrease significantly after treatment with extract.
      After 12 days of treatment with the extract, glucose tolerance increased
      significantly, and overall blood glucose exposure calculated as area under the
      curve (AUC) decreased 53.4% (P < 0.01) in db/db mice. Furthermore, db/db mice
      treated with extract (150 mg/kg body wt.) showed weight loss from 51.0+/-1.9 g on
      Day 0, to 46.6+/-1.7 g on Day 5, and to 45.2+/-1.4 g on Day 12 (P < 0.05 and P <
      0.01 compared to Day 0, respectively). The body weight of lean littermates also
      decreased at the same dose of extract. These data suggest that Panax ginseng
      berry extract may have therapeutic value in treating diabetic and obese patients.

PMID- 12046871
TI  - Treatment of hyperopia: a new ablation profile to reduce corneal eccentricity.
AB  - PURPOSE: Hyperopic treatment normally increases corneal eccentricity (the measure
      of corneal asphericity). Information derived from treating corneal white scars
      occurring after hyperopic ablations suggests that reducing corneal eccentricity
      through central corneal flattening followed by smoothing eliminates scarring and
      prevents its recurrence. METHODS: We treated two groups of patients; Group 1
      included 18 eyes of 18 patients with whitish corneal scar due either to
      photorefractive keratectomy (PRK) (n = 16, 88.9%) or laser in situ keratomileusis
      (LASIK) (n = 2, 11.1%). Mean preoperative spherical equivalent refraction was
      +1.20 +/- 2.30 D, and mean corneal eccentricity was +1.2 +/- 0.8. We performed
      phototherapeutic keratectomy (PTK) to achieve central corneal flattening and
      decrease corneal eccentricity, coupled with smoothing, using the Nidek EC-5000
      excimer laser. Group 2 included 27 eyes of 27 consecutive patients with mean
      preoperative spherical equivalent refraction of +2.40 +/- 1.30 D; these patients
      had laser epithelial keratomileusus (LASEK) with the Nidek EC-5000 excimer laser.
      A new Nidek aspheric ablation profile with a wider optical zone (6.7 mm) and
      transition zone (9.5 to 10.00 mm) was applied. RESULTS: In Group 1 eyes, the
      apical scar disappeared in all eyes. Postoperative spherical equivalent
      refraction was +1.8 +/- 1.02 D and mean postoperative eccentricity was +0.9. In
      Group 2 eyes after 9 months of follow-up, mean postoperative spherical equivalent
      refraction was -0.30 +/- 0.30 D, with no loss of lines of BSCVA. Low corneal
      eccentricity values were maintained, which created a gradual change in the rate
      of curvature. CONCLUSIONS: The new Nidek profile for hyperopia treatment allowed
      successful refractive correction and maintained low eccentricity values that
      approached those of a normal cornea.

PMID- 12046870
TI  - Effects of intrinsic fluorescence and quenching on fluorescence-based screening
      of natural products.
AB  - To evaluate the effects of intrinsic (natural) fluorescence and quenching as
      confounding variables in fluorescence-based enzyme inhibition assays of natural
      products, we measured the fluorescence and quenching properties of 25 components
      of popular herbal products. The analyses were performed under conditions
      typically employed in drug-drug interaction studies that use c-DNA-derived P450
      isoforms and surrogate fluorogenic substrates. Four of the 25 compounds tested
      (isorhamnetin, quercetin, vitexin, and yangonin) fluoresced or quenched
      sufficiently to interfere with these assays. Intrinsic fluorescence had a greater
      effect on these assays than quenching and for one compound, yangonin, was
      sufficient to mask inhibition and potentially produce a false negative result.
      Quenching had less of an effect on these assays, but was significant enough for
      one compound, quercetin, to mimic "weak" inhibition. Therefore, because intrinsic
      fluorescence or quenching could render some natural products unsuitable for
      testing in certain fluorometric assays, it would be prudent to include an
      evaluation of these properties in experimental protocols.

PMID- 12046872
TI  - Laser in situ keratomileusis and diode thermal keratoplasty for correction of
      hyperopia from +5.00 to +10.00 diopters.
AB  - PURPOSE: To evaluate the effects and safety of laser in situ keratomileusis
      (LASIK) and diode thermal keratoplasty (DTK) for correction of moderate to high
      hyperopia (+5.00 to +10.00 D). METHODS: This prospective study included 30 eyes
      of 15 patients who had LASIK-DTK bioptics. The median age of the patients was
      50.5 years. LASIK was performed using a Nidek EC-5000 excimer laser system and
      DTK by a Prolaser DTK laser, 2 months after LASIK. Follow-up ranged from 9 to 12
      months (mean, 10.5 mo). RESULTS: The mean preoperative spherical equivalent
      refraction was +8.25 +/- 0.25 D and mean postoperative was +1.00 +/- 0.50 D. The
      preoperative best spectacle-corrected visual acuity (BSCVA) was < or = 20/40 in
      10 eyes and > or = 20/25 in 20 eyes. Postoperatively, BSCVA was < or = 20/40 in 8
      eyes and > or = 20/25 in 22 eyes. No significant intra- or postoperative
      complications occurred. CONCLUSION: LASIK-DTK bioptics for correction of moderate
      to high hyperopia (+5.00 to +10.00 D) was safe and effective. In this method, two
      different ablative and non-ablative laser systems were used to compensate for
      regression, which is the most important concern in the correction of hyperopia.

PMID- 12046873
TI  - Laser in situ keratomileusis with the Nidek EC-5000 excimer laser for astigmatism
      greater than 4.00 D.
AB  - PURPOSE: To evaluate laser in situ keratomileusis (LASIK) performed with the
      Nidek EC-5000 excimer laser in 66 astigmatic eyes with cylinder from 4.00 to 8.00
      D. METHODS: LASIK was performed with the Nidek EC-5000 excimer laser in 66
      astigmatic eyes with cylinder from 4.00 to 8.00 D. Based on Chayet's nomogram,
      ablation zone diameters were 5.5 mm (steep meridian ablation) to 7.5 mm (flat
      meridian ablation). In eyes with simple myopic astigmatism, mixed astigmatism,
      and compound myopic astigmatism (low sphere), ablation was performed in both
      meridians. In eyes with simple hyperopic astigmatism, ablation was performed in
      the flat meridian alone. In eyes with compound hyperopic astigmatism, ablation
      zone diameter was 5.5 mm and the transition zone was 7.5 mm. RESULTS: Uncorrected
      visual acuity was 20/40 or better in 89% of eyes and was equal to preoperative
      best spectacle-corrected visual acuity in 62% of eyes. No eyes lost lines of best
      spectacle-corrected visual acuity. CONCLUSIONS: Using the Nidek EC-5000 excimer
      laser, we had satisfactory results in the treatment of astigmatic eyes with
      cylinder from 4.00 to 8.00 D, based on Chayet's nomogram.

PMID- 12046874
TI  - Nomogram for treatment of astigmatism with laser in situ keratomileusis.
AB  - PURPOSE: Laser in situ keratomileusis (LASIK) is a mainstay in refractive
      surgery. Myopes and compound myopic astigmats generally have a good result after
      LASIK. However, simple myopic astigmats are sometimes not as pleased with their
      visual outcome. METHODS: We analyzed 40 patients who underwent LASIK with the
      Nidek EC-5000 excimer laser and the Hansotome microkeratome. The key to
      successful LASIK in these patients was proper analysis of corneal topography.
      RESULTS AND CONCLUSION: We found that 37 of the 40 patients studied had an
      excellent result, but poor topographic interpretation gave a poorer result in the
      remaining three patients. We discuss how to correctly interpret corneal
      topography and proper case selection and patient counseling.

PMID- 12046875
TI  - Geometric ray tracing for design of customized ablation in laser in situ
      keratomileusis.
AB  - PURPOSE: By means of an individualized optical model of the visual system, a
      customized surgical correction is proposed to achieve emmetropia and best visual
      acuity. METHODS: The study included 64 eyes with myopia or myopic astigmatism
      that underwent LASIK with the Nidek EC-5000 excimer laser. The mean age was 33
      years (19 to 54 yr). Mean myopia was -3.70 D (0 to -7.50 D) and mean astigmatism
      was -0.90 D (0 to -4.00 D). The model included a personalized Le Grand eye model,
      a geometric ray tracing process, and a statistical study of postoperative corneal
      flattening. As a final result, the model provided an interval of corneal radius
      to be sculpted in the stroma to maximize visual acuity attainable without
      correction. The mean radius of the interval was used to obtain the sphere
      cylinder correction. RESULTS: In 100% of eyes with 0 to +0.50 D of residual
      spherical equivalent refraction (n = 39), the sculpted radius was inside the
      surgical interval and in the 30% of the "non-satisfactory" surgeries (7/25 eyes)
      the sculpted radius was outside the interval. CONCLUSIONS: An objective optical
      method has been developed to obtain a customized ablation for LASIK.

PMID- 12046876
TI  - Comparison of wavefront-guided customized ablation vs. conventional ablation in
      laser in situ keratomileusis.
AB  - PURPOSE: To compare visual outcome after applying wavefront-guided customized
      ablation with conventional ablation in laser in situ keratomileusis (LASIK)
      patients. METHODS: We performed a prospective, randomized controlled study that
      included 22 eyes of 11 patients who were treated with LASIK using the Nidek EC
      5000 excimer laser system. We applied wavefront-guided customized ablation (study
      group) in the first eye of each patient. The conventional ablation (control
      group) was performed in the other eye of the same patient. Best spectacle
      corrected visual acuity (BSCVA), spherical equivalent refraction, and high-order
      aberrations were evaluated preoperatively and at 1 month. High-order aberrations
      were measured using the Nidek OPD-Scan. RESULTS: Preoperative and 1-month
      postoperative BSCVA were better than 20/40 (100%) after LASIK with both
      conventional ablation (control) and wavefront-guided customized ablation.
      Preoperatively, mean high-order aberrations in the control group were 0.572 and
      in the study group, 0.428 (Zernike coefficient unit). One-month after LASIK, mean
      high-order aberrations in the control group were 0.496 and in the study group,
      0.476 (Zernike coefficient unit). We found no statistically significant
      difference between preoperative and 1-month postoperative high-order aberrations
      in either group. CONCLUSION: LASIK with both conventional ablation and wavefront
      guided customized ablation resulted in the same BSCVA 1 month after LASIK.
      Preoperative and 1-month postoperative high-order aberrations were not
      statistically different following LASIK between ablation types.

PMID- 12046877
TI  - Bioptics in phakic and pseudophakic intraocular lens with the Nidek EC-5000
      excimer laser.
AB  - PURPOSE: To evaluate predictability, safety, stability, and complications related
      to bioptics in patients that received phakic and those that received pseudophakic
      intraocular lenses. Both groups had LASIK with the Nidek EC-5000 excimer laser
      following IOL implantation. METHODS: We evaluated retrospectively 281 eyes of 196
      patients with posterior chamber phakic implantation (ICL) and 64 pseudophakic
      eyes of 55 patients. All patients had LASIK 1 month or more after the first
      surgery. We used a treatment zone of 5.5 mm with a 7.00-mm transition zone. The
      flap was made with the Automated Corneal Shaper (ACS). RESULTS: In the group of
      phakic ICL eyes with bioptics, preoperative mean spherical equivalent refraction
      was -5.50 D (range, -1.37 to -16.00 D). The first day after LASIK, mean spherical
      equivalent refraction was -0.06 D, and at 1 month, -0.40 D. In pseudophakic
      bioptics eyes, preoperative mean spherical equivalent refraction was -2.61 D
      (range, +0.50 to -5.50 D). The first day after LASIK it was +0.27 D, and 1 month
      after LASIK it was +0.09 D. The incidence of complications was similar in both
      groups of patients. The most frequent complication was keratitis sicca
      (approximately 10% in each group). Interstitial edema (2.1%) was present only in
      phakic bioptics eyes. No retinal complications were observed. Refraction was
      stable 4 years after surgery. Target achieved refraction was +/- 0.50 D, showing
      the predictability of the procedure. CONCLUSIONS: Predictability and safety were
      demonstrated according to results and absence of severe complications related
      with this technique. Older patients did not develop more complications than
      younger people; dry eye incidence was similar in both groups. In extreme myopia
      patients did not present retinal complications related to surgical procedures.

PMID- 12046878
TI  - Effects of laser plume evacuation on laser in situ keratomileusis outcomes.
AB  - PURPOSE: To study the effects laser plume evacuation on LASIK outcomes using a
      surgical vacuum and the Nidek EC-5000 excimer laser. METHODS: Three-month LASIK
      postoperative data were evaluated retrospectively for 117 eyes treated with a
      laser plume evacuator and 82 eyes treated without a laser plume evacuator. All
      eyes were treated with the same Moria CB microkeratome and the same Nidek-EC 5000
      excimer laser using the same nomogram. RESULTS: No statistically significant
      difference was noted in the frequency of corneal abrasions, flap slippage, or the
      level of postoperative interface debris. A statistically significant difference
      (P < .001) was noted in postoperative residual refractive error and uncorrected
      visual acuity. In the group treated without a plume evacuator, 65% (n = 53) were
      within +/- 0.50 D of the intended correction, 59% (n = 48) had an uncorrected
      visual acuity of 20/20 or better, 68% (n = 56) had an uncorrected visual acuity
      of 20/25 or better, and 90% (n = 73) had an uncorrected visual acuity of 20/40 or
      better. In the group treated with a plume evacuator, 92% (n = 108) were within +/
      0.50 D of the intended correction, 74% (n = 87) had an uncorrected visual acuity
      of 20/20 or better, 89% (n = 104) had an uncorrected visual acuity of 20/25 or
      better, and 96% (n = 112) had an uncorrected visual acuity of 20/40 or better.
      CONCLUSION: Laser plume evacuation using surgical tubing and a surgical vacuum
      improved refractive and uncorrected visual acuity outcomes following LASIK.

PMID- 12046879
TI  - Comparison of laser in situ keratomileusis outcomes with the Nidek EC-5000 and
      Meditec Mel 70 excimer lasers.
AB  - PURPOSE: To report refractive outcomes of laser in situ keratomileusis (LASIK)
      for myopia with and without astigmatism using the Nidek EC-5000 and Meditec Mel
      70 excimer laser systems. METHODS: A retrospective analysis of refractive
      outcomes with each laser was conducted. Approximately 5700 eyes treated for
      myopia and myopic astigmatism were analyzed. Preoperative sphere ranged from 
      0.25 to -15.50 D and cylinder ranged from -0.75 to -5.50 D. All statistical
      analyses were performed by Datagraph med version 2.8 refractive analysis
      software. RESULTS: With the Nidek EC-5000 at 6 months after LASIK, mean spherical
      equivalent refraction was -0.24 D with 72% of eyes within +/- 0.50 D. In the
      Meditec cohort, the mean spherical equivalent was -0.54 D with 55% of eyes +/-
      0.50 D. CONCLUSION: Eyes treated for myopia and astigmatism with either of these
      lasers showed early refractive stability and similar efficacy. Higher incidences
      of epithelial ingrowth and haze were present in the Meditec treated eyes.

PMID- 12046880
TI  - Predictability of corneal flap thickness in laser in situ keratomileusis using
      three different microkeratomes.
AB  - PURPOSE: To compare the accuracy and consistency of corneal flap thickness in the
      right and left eye created by three different widely used microkeratomes during
      consecutive laser in situ keratomileusis (LASIK). METHODS: Corneal thickness of
      132 eyes of 66 patients was measured preoperatively and intraoperatively. Corneal
      flap thickness was calculated by subtracting the corneal stromal thickness from
      the total corneal thickness. Three different microkeratomes were used for
      creating the corneal flap: Chiron Automated Corneal Shaper (ACS), Baush and Lomb
      Surgical Hansatome, and Nidek MK 2000 microkeratomes. The same surgeon performed
      all procedures on the right eye first and then on the left eye using the same
      blade and the same surgical technique. RESULTS: Mean corneal flap thickness
      created by the ACS (160-microm depth setting) microkeratome was 128.30 +/- 12.57
      microm in the right eye and 122.96 +/- 13.30 microm in the left eye. The
      Hansatome (160-microm depth plate) microkeratome created a flap of mean 141.16 +/
      20.11 microm in the right eye and 120.95 +/- 26.95 microm in the left eye, and
      the Nidek MK 2000 (130-microm depth plate) microkeratome created a flap of 127.25
      +/- 4.12 microm in the right eye and 127.54 +/- 3.7 microm in the left eye.
      CONCLUSION: Corneal flap thickness tended to be considerably thinner than
      expected on both eyes using the ACS and Hansatome. With the ACS and Hansatome,
      the difference in corneal flap thickness between the first and second operated
      eye was statistically significant. With the Nidek MK 2000 microkeratome, there
      was no statistically significant difference between the first and second operated
      eye and measurements were close to desired corneal flap thickness. Intraoperative
      pachymetry is recommended for every LASIK procedure.

PMID- 12046881
TI  - Clinical experience with the customized low spherical aberration ablation profile
      for myopia.
AB  - PURPOSE: To evaluate postoperative spherical aberration reduction and increase of
      visual acuity with new Flex Scan and custom ablation software. METHODS: We
      created a new customized low spherical aberration ablation profile for myopic
      patients (true spherical ablation). This aspheric algorithm increases ablation in
      the midperiphery and periphery to reduce surgery-induced spherical aberration.
      LASIK was performed in 143 eyes, 127 with the true spherical ablation profile,
      and 16 with the custom true spherical ablation profile. We used the Nidek OPD
      Scan and the Nidek EC-5000 excimer laser. Ablation zones of 6.0 to 6.5 mm and
      transition zones of 8.5 to 9.0 mm were used. Preoperative myopia was as much as 
      6.50 D, and astigmatism, -2.50 D. RESULTS: In the true spherical ablation profile
      group, 37.8% of eyes achieved UCVA better than 1.0 (1.2 to 2.0). In custom true
      spherical ablation profile eyes, 62.5% achieved UCVA better than 1.0 (1.2 to
      1.5). One patient had on the day after surgery (true spherical ablation profile)
      an UCVA of 3.0 (preoperative UCVA was 0.1 and BSCVA was 1.0 in each eye).
      Preoperative and postoperative OPD-Scan analysis showed reduction of spherical
      like aberrations for dilated pupil after surgery or insignificant changes for
      most patients. No patient had any complaints concerning quality of vision.
      CONCLUSION: LASIK based on our true spherical ablation profile produced good
      visual acuity results for myopic patients.

PMID- 12046882
TI  - Nidek MK 2000 microkeratome clinical evaluation.
AB  - PURPOSE: To evaluate flap dimension, flap thickness, hinge size, and cut
      deterioration with second blade use with the Nidek MK 2000 automatic
      microkeratome. METHODS: The Nidek MK 2000 with different head options (130 and
      160 microm) and suction rings (8.5 and 9.5 mm) was used during 328 consecutive
      LASIK procedures, reusing the blade for the second eye in the same patient. Flap
      diameter and hinge size were measured under microscopy with a Castroviejo caliper
      and thickness was calculated using the Pachete ultrasonic pachymeter. RESULTS:
      The mean flap thickness was 116.03 +/- 19.26 microm using the 130-microm head and
      147.7 +/- 21.74 microm using the 160-microm head. The average vertical flap size
      was 8.56 +/- 0.36 mm with the 8.5-mm suction ring and 9.45 +/- 0.32 mm with the
      9.5-mm ring. The hinge size was 4.7 +/- 0.72 mm. The second cut was thinner than
      the first; 14.7 microm average using the 130-microm head, and 19.1 microm average
      using the 160-microm head. CONCLUSION: The Nidek MK 2000 microkeratome was
      simple, safe, predictable, and reliable for LASIK.

PMID- 12046884
TI  - Antioxidant activity of tear fluid and antioxidant therapy in myopic patients
      after laser in situ keratomileusis.
AB  - PURPOSE: To study the antioxidant activity of the tear fluid after laser in situ
      keratomileusis (LASIK). METHODS: Antioxidant activity of the tear fluid was
      investigated in 12 eyes of seven patients with myopia who underwent LASIK. All
      patients were treated with the Nidek EC-5000 excimer laser using the Chiron
      Vision Hansatome HT-230 microkeratome. The hemoluminescence method for assessment
      of antioxidant activity of tear fluid was used. RESULTS: Increase in antioxidant
      activity of tear fluid was found in 50% of eyes and decrease was found in 25% of
      eyes on day 4 after surgery. In 25% of eyes, antioxidant activity did not change.
      Parameters of antioxidant activity returned approximately to preoperative levels
      in 75% of eyes on the 7th day. In eyes with increased antioxidant activity on the
      7th day, signs of epitheliopathy and light dystrophic corneal flap changes were
      found. Topical use of antioxidants led to clinical improvement. CONCLUSIONS: In
      eyes with epithelial or corneal flap problems after LASIK, we recommend 2-week
      antioxidant therapy for cornea protection from oxygen-derived free radicals.

PMID- 12046883
TI  - Cleaning solutions as a cause of diffuse lamellar keratitis.
AB  - PURPOSE: To assess the capability of two microkeratome cleaning solutions in
      causing diffuse lamellar keratitis (DLK) in a rabbit model of laser in situ
      keratomileusis (LASIK). METHODS: Two cleaning solutions (Palmolive 2:100 and
      Cidezyme 2:250) were tested. These solutions were diluted with balanced salt
      solution according to directions from the Hansatome microkeratome manual. Two
      additional solutions were prepared using an additional ten-fold dilution,
      creating a total of four study solutions. A LASIK flap was created in one eye
      each of 25 rabbits using the ALK Chiron microkeratome. The rabbits were divided
      into five study groups. The flaps were reflected and a drop of one of the study
      solutions (or BSS, control group) was placed on the interface. After 1 minute,
      the solution was washed out from the interface and the flap was repositioned. The
      eyes were examined at the slit lamp on postoperative days 1, 2, 3, 5, and 7.
      RESULTS: In 12 eyes, a flap displacement was identified. Four eyes showed flap
      retraction and five others, epithelial ingrowth in flap margins. The incidence of
      these events did not differ among groups. Thirteen eyes were then evaluated for
      DLK. No DLK-like interface inflammation was seen in the studied eyes. CONCLUSION:
      The cleaning solutions, when diluted as recommended by the microkeratome
      manufacturer, when in contact with the corneal stroma, and provided that the
      interface was washed with BSS did not cause DLK interface inflammation in rabbit
      LASIK models.

PMID- 12046885
TI  - Reduction of spherical aberration: experimental model of photoablation.
AB  - PURPOSE: Several authors have suggested that a compound ablation for myopia may
      reduce postoperative spherical aberration. This technique consists of treating
      myopic ablation by increasing the preoperative sphere 25% and applying a
      hyperopic ablation of 25% of preoperative sphere. Theoretically, this technique
      allows optical zone increase, and elimination of the peripheral red ring.
      METHODS: Eight eyes of four patients with bilateral moderate myopia received
      laser epithelial keratomileusus (LASEK) with the Nidek EC-5000 excimer laser. In
      each patient, one eye was treated with the compound ablation (Group 1), and the
      fellow eye with the standard cross-cylinder technique (Group 2). Mean
      preoperative refraction and BSCVA were comparable within the two groups. RESULTS:
      At 1 month postoperatively, UCVA was significantly better in Group 2 than in
      Group 1 eyes. In neither group was clinically important haze seen. Subjectively,
      all patients rated more satisfactorily the eye that received the standard
      ablation (Group 2) than the one treated with compound ablation (Group 1).
      Evaluation of keratorefractive indices derived from corneal topography revealed
      significantly better eccentricity in Group 2 eyes. Corneal topography showed the
      presence of a central island in all Group 1 eyes. CONCLUSION: The compound
      ablation hypothesis was not confirmed. Presence of central island in compound
      treated eyes induced significant optical aberrations.

PMID- 12046886
TI  - Butterfly laser epithelial keratomileusis for myopia.
AB  - PURPOSE: Decreased epithelial viability is a postoperative complication of
      standard laser epithelial keratomileusis (LASEK) that hampers rapid recovery, and
      causes reduced visual acuity as well as discomfort. We present a new LASEK
      technique that, by increasing epithelial viability, reduces the occurrence of
      these complications. METHODS: In a preliminary series of patients, conventional
      LASEK was performed in one eye, and "Butterfly" LASEK in the fellow eye. In
      Butterfly LASEK, a thin paracentral epithelial line, from 8 to 11 o'clock was
      removed, and 20% alcohol plus BSS 'solution was placed in contact with the cornea
      for 5 to 30 seconds. A specially designed spatula allowed separation of
      epithelium from Bowman's layer, proceeding from center to periphery on both
      sides. A special retractor was used to move the two flaps of loose epithelium
      toward the limbus. After drying the surface, excimer laser ablation was performed
      with the Nidek EC-5000 excimer laser. Smoothing with masking solution was then
      carried out, followed by flap replacement and overlapping. RESULTS: We treated 70
      eyes of 35 patients with Butterfly LASEK. Preoperative mean spherical equivalent
      refraction was -5.30 +/- 3.70 D. At 12 months after surgery, mean spherical
      equivalent refraction was -0.10 +/- 0.40 D, and no lines of BSCVA were lost.
      Ninety percent of patients preferred Butterfly LASEK to conventional LASEK
      because of increased comfort. At 12 months, no patient had more than trace haze,
      and in 96.2%, corneas were completely clear. CONCLUSIONS: Butterfly LASEK is
      aimed at preserving the limbal connection of epithelial stem cells and limbal
      vascular connections. Improved epithelial viability is thus achieved, with faster
      postoperative recovery.

PMID- 12046888
TI  - Applications of confocal microscopy in refractive surgery.
AB  - PURPOSE: To evaluate applications of the Confoscan 2.0, a computerized confocal
      optical microscopy system by Nidek, in refractive surgery. METHODS: We used the
      Confoscan 2.0 to evaluate the tissue reparative response after PRK, LASEK, and
      LASIK in 60 eyes of 40 patients. Confoscan 2.0 provided highly detailed images of
      the corneal layers, up to the cellular level. Furthermore, it measured corneal
      thickness as well as precise positioning of each single recorded corneal layer.
      The Confoscan was also used to analyse the LASIK flap. RESULTS: Findings in the
      transition zone between epithelium and anterior stroma in PRK and LASEK eyes were
      divided into two groups: Group 1, with marked hyper-reflectivity, and Group 2,
      with less hyper-reflectivity, similar to normal eyes. Group 2 eyes belonged to
      patients that underwent smoothing with a masking solution after ablation. Group 1
      eyes received no smoothing. In LASIK eyes, we evaluated the quality of the flap
      interface. Hyper-reflecting specks could be observed in the interface, showing a
      tendency to decrease over time. Depth of the LASIK flap was measured, and showed
      variable thickness with all microkeratomes tested. CONCLUSION: We hypothesize
      that a more regular corneal surface, obtained with smoothing in PRK and LASEK,
      allows a better reparative response after refractive surgery. In LASIK eyes, the
      Confoscan provided precise measurement of the residual stromal bed, information
      particularly valuable for the prevention of ectasia in retreatments.

PMID- 12046887
TI  - Use of amino acids in refractive surgery.
AB  - PURPOSE: To assess the influence of amino acid supplements on corneal fibroblast
      activity during corneal healing in patients with chronic ulcers, as well as after
      refractive surgery when delayed re-epithelialization had been observed in the
      fellow eye. METHODS: Studies were conducted in vitro on eye bank eyes, and in
      vivo. In vitro cultures of rabbit corneal fibroblasts were enriched with
      progressively higher concentrations of amino acids. The human eye bank cornea
      study involved corneal epithelium removal, with corneas kept for 7 days in
      standard storage medium, either simple or enriched with amino acids. Clinical
      studies included treatment of two groups: Group 1 included six eyes of six
      patients with chronic epithelial defects, resistant to usual treatment; Group 2
      included 21 eyes of 21 patients with delayed re-epithelialization after PRK in
      the first eye (12 +/- 3 days). Group 1 was treated for 1 month, and Group 2
      received treatment preoperatively and postoperatively after surgery in the fellow
      eye until re-epithelialization was achieved. All patients received 13 amino acids
      and Vitamin C in three tablets, three times per day. RESULTS: Cultures of rabbit
      corneal fibroblasts showed that progressively increasing amino acid supplements
      led to an increase in the percentage of fibroblasts. De-epithelialized human eye
      bank corneas incubated with amino acids showed thicker and better organized re
      epithelialization when compared to corneas incubated in simple standard storage
      media. In the clinical study, five eyes in Group 1 showed substantial
      improvement, one eyes remained unchanged. All eyes in Group 2 showed complete re
      epithelialization within 60 hours after surgery. CONCLUSION: Results suggest
      improvement of re-epithelialization when an increase of serum and tear film amino
      acids is obtained through oral administration.

PMID- 12046889
TI  - Corneal pharmacodynamics after photorefractive keratectomy and laser in situ
      keratomileusis in rabbits.
AB  - PURPOSE: To evaluate changes in corneal pharmacodynamics after PRK and LASIK in
      rabbits. METHODS: Two groups of five rabbits (10 eyes) each received PRK and
      LASIK, and an unoperated third group was used as a control. Dexamethasone,
      efflumidex, diclofenac, and tobramycin were applied. Anterior chamber aqueous was
      collected every 20 minutes and analyzed by spectrophotometry. Histological
      studies were performed to find drug deposits in the cornea. RESULTS: The
      coefficient of diffusion after PRK was determined for dexamethasone (3.2 x 10(-4)
      cm/min), efflumidex (1.4 x 10(-4)), diclofenac (7.4 x 10(-5)), and tobramycin
      (5.4 x 10(-6)). After LASIK, the coefficient of diffusion for dexamethasone was
      3.4 x 10(-5); efflumidex, 1.7 x 10(-5); diclofenac, 8.8 x 10(-6); and tobramycin,
      2.4 x 10(-6) cm/min. Total time of passing through the cornea after PRK and LASIK
      was also measured: dexamethasone 45 and 70 min, efflumidex 50 and 115 min,
      diclofenac 60 and 200 min, and tobramycin 335 and 690 min. Histologically a drug
      deposit area was found in corneas after LASIK under the flap. In the control
      group, coefficient of diffusion for dexamethasone was 1.2 x 10(-5) cm/min,
      efflumidex 1.5 x 10(-5), diclofenac 6.4 x 10(-6), and tobramycin 2.1 x 10(-6).
      Total time of passing through the cornea for the control group for dexamethasone
      was 60 min, efflumidex 105 min, diclofenac 160 min, and tobramycin 540 min.
      CONCLUSIONS: Coefficient of diffusion increased after photorefractive surgery.

PMID- 12046890
TI  - Clinical applications of the OPD-Scan wavefront aberrometer/corneal topographer.

PMID- 12046891
TI  - Pluronic block copolymers in drug delivery: from micellar nanocontainers to
      biological response modifiers.
AB  - Pluronic block copolymers are recognized pharmaceutical excipients listed in the
      US and British Pharmacopoeia. The incorporation of drugs into Pluronic micelles
      results in increased solubility and stability of drugs. Consequently, the
      micelles are used for delivery of drugs in the body. Pluronic unimers sensitize
      multidrug-resistant cells by inhibiting drug efflux transporters. This allows for
      the development of formulations for the treatment of multidrug-resistant and
      metastatic tumors. Furthermore, these formulations can be used to enhance brain
      and oral bioavailability of various drugs. Finally, Pluronic formulations were
      shown to enhance transgene expression in the body. This opens new possibilities
      for the use of Pluronic in gene therapies.

PMID- 12046892
TI  - Recent advances in the stabilization of proteins encapsulated in injectable PLGA
      delivery systems.
AB  - Injectable controlled-release systems based on biodegradable copolymers of lactic
      and glycolic acids (PLGAs) have become widely used for delivery of protein
      therapeutics and vaccine antigens. Over the last five years, great strides have
      been made toward overcoming the difficulty of stabilizing PLGA-encapsulated
      proteins. In addition to stabilizing proteins during encapsulation with anhydrous
      methods, two approaches have proven highly effective to stabilize proteins during
      1-month release incubation under physiological conditions: protein complexation
      with zinc and control of PLGA microclimate pH with antacid excipients. Described
      here are recent advances in the stabilization of proteins encapsulated in PLGA
      delivery systems.

PMID- 12046893
TI  - Mechanosensitive channels of bacteria and archaea share a common ancestral
      origin.
AB  - The ubiquity of mechanosensitive (MS) ion channels set off a search for their
      functional homologues in archaea, the third domain of life. A new MS channel was
      identified in the archaeon Methanococcus jannaschii by using the TM1
      transmembrane domain of the bacterial MS channel of large conductance, MscL, as a
      genetic probe to search the archaeal genomic database for MS channel homologues.
      The hypothetical protein MJ0170 (MscMJ) was found to harbor two MscL-like TM1
      structural motifs and showed a high degree of se quence and secondary structure
      conservation with MscS (YggB) homologues. The alignment of sequences of MscL,
      MscS and MscMJ homologues further revealed that bacterial and archaeal channels
      form a phylogenetic tree composed of three main branches and share a common
      ancestral origin. This suggests the evolution of prokaryotic MS channels via gene
      duplication of a MscL-like progenitor gene followed by divergence, fur ther
      indicating that the common ancestor of the prokaryotic MS channels most likely
      resembled MscL. When expressed in E. coli and functionally examined by the patch
      clamp, the MscMJ protein behaved as a MS channel with a conductance of 270 pS in
      200 mM KCl and a cation selectivity (PK/PC]) of approximately 6. The structural
      and functional homologue of MscMJ, MscMJLR, was identified as a second type of MS
      channel in M. jannaschii. The channel has a conductance of approximately 2 nS,
      rectifies with voltage and shares cation selectivity with MscMJ. The
      stoichiometry of both types of MS channels revealed that the free energy of
      activation, deltaG0 approximately 7kT, obtained for MscMJ matches the one
      calculated for MscS, deltaG0 approximately 5kT, whereas the free energy of
      activation approximately deltaG0 approximately 18kT of MscMJLR resembles more the
      deltaG0 = 14-19kT reported for MscL. The presence of two types of MS channels
      discovered in the cell envelope of M. jannaschii indicates that multiplicity of
      MS channels in prokaryotes is a necessary element for their survival in the
      habitats frequently challenged by sudden changes in osmolarity. Further
      functional and phylogenetic study of MS channels from all three domains of the
      universal phylogenetic tree may help to understand the evolution and common
      biophysical principles that govern mechanosensory transduction.

PMID- 12046894
TI  - The structural basis for amyloid formation by plasma apolipoproteins: a review.
AB  - The formation of amyloid and other protein deposits in vivo is synonymous with
      many pathological conditions such as Alzheimer's disease, Creutzfeldt-Jakob
      disease and Parkinson's disease. Interestingly, many plasma apolipoproteins are
      also associated with amyloid deposits, including apolipoprotein (apo) A-I, apoA
      II and apoE. Apolipoproteins share a number of structural and conformational
      properties, namely a large proportion of class A amphipathic alpha-helices and
      limited conformational stability in the absence of lipid. Other proteins that
      form amyloid such as alpha-synuclein and serum amyloid A also contain amphipathic
      alpha-helical domains similar to those found in apolipoproteins. In this review
      we develop a hypothesis to account for the widespread occurrence of
      apolipoproteins in amyloid deposits. We describe the conformational stability of
      human apoC-II and the stabilization of alpha-helical structure in the presence of
      phospholipid. We propose that lipid-free apoC-II forms partially folded
      intermediates prone to amyloid formation. Parameters that affect apolipoprotein
      lipid binding in vivo, such as protein and lipid oxidation or protein truncations
      and mutations, could promote apolipoprotein-related pathologies including those
      associated within amyloid deposits of atherosclerotic plaques.

PMID- 12046895
TI  - Amiloride derivatives block ion channel activity and enhancement of virus-like
      particle budding caused by HIV-1 protein Vpu.
AB  - The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion
      channels and enhances the process of virion budding and release. Mutagenesis
      studies have shown that the N-terminal transmembrane domain primarily controls
      both of these activities. Here we report that the Vpu ion channel is inhibited by
      the amiloride derivatives 5-(N,N-hexamethylene)amiloride and 5-(N,N
      dimethyl)amiloride but not by amiloride itself, nor by amantadine.
      Hexamethyleneamiloride also inhibits budding of virus-like particles from HeLa
      cells expressing HIV-1 Gag and Vpu proteins. These results confirm the link
      between Vpu ion channel activity and the budding process and also suggest that
      amiloride derivatives might have useful anti-HIV-1 properties.

PMID- 12046896
TI  - Fluorescence photobleaching analysis for the study of cellular dynamics.
AB  - The wide availability of the confocal microscope and the emergence of green
      fluorescent protein (GFP) transfection technology has led to the increasing use
      of photobleaching studies to examine aspects of cellular dynamics in living
      cells. In this review, we examine the theory and practice of performing
      photobleaching studies using a confocal microscope. We illustrate the application
      of photobleaching protocols using our own measurements of fluorescently labelled
      red blood cells and of malaria parasite-infected erythrocytes expressing GFP
      fusions and examine other examples from the literature.

PMID- 12046897
TI  - Kinetics of phospholipid insertion into monolayers containing the lung surfactant
      proteins SP-B or SP-C.
AB  - The lung surfactant proteins SP-B and SP-C are pivotal for fast and reversible
      lipid insertion at the air/liquid interface, a prerequisite for functional lung
      activity. We used a model system consisting of a preformed monolayer at the
      air/liquid interface supplemented with surfactant protein SP-B or SP-C and
      unilamellar vesicles injected into the subphase of a film balance. The content of
      SP-B or SP-C was similar to that found in lung lavage. In order to elucidate
      distinct steps of lipid insertion, we measured the time-dependent pressure
      increase as a function of the initial surface pressure, the temperature and the
      phosphatidylglycerol content by means of surface tension measurements and
      scanning force microscopy (SFM). The results of the film balance study are
      indicative of a two-step mechanism in which initial adsorption of vesicles to the
      protein-containing monolayer is followed by rupture and integration of lipid
      material. Furthermore, we found that vesicle adsorption on a preformed monolayer
      supplemented with SP-B or SP-C is strongly enhanced by negatively charged lipids
      as provided by DPPG and the presence of Ca2+ ions in the subphase. Hence, long
      range electrostatic interactions are thought to play an important role in
      attracting vesicles to the surface, being the initial step in replenishment of
      lipid material. While insertion into the monolayer is independent of the type of
      protein SP-B or SP-C, initial adsorption is faster in the presence of SP-B than
      SP-C. We propose that the preferential interaction between SP-B and negatively
      charged DPPG leads to accumulation of negative charges in particular regions,
      causing strong adhesion between DPPG-containing vesicles and the monolayer
      mediated by Ca2+ ions, which eventually causes flattening and rupture of attached
      liposomes as observed by in situ SFM.

PMID- 12046898
TI  - Hydration and thermal reversibility of glycolipids depending on sugar chains.
AB  - To elucidate a relationship between the structural properties and hydration
      characteristic of gangliosides, time-resolved small-angle X-ray scattering
      measurements using synchrotron radiation have been performed on aqueous
      dispersions of various types of gangliosides (GM1, GD1a, GD1b and GM3) under a
      constant heating (5-65 degrees C) and cooling (65-5 degrees C) rate. In the case
      of GM3, they formed a vesicular aggregate with a high structural reversibility in
      the heating-and-cooling process. For the micelles of GM1, GD1a and GDlb, we found
      an evident thermal hysteresis in the structural changes of their headgroups and
      evaluated quantitatively the amounts of water molecules occluded in the micellar
      hydrophilic regions by using the shell modeling method reported previously. For
      all cases of GM1, GD1a and GD1b, the thickness of the hydrophilic region of the
      micelle shrunk after the heating process, and stayed mostly constant over the
      entire cooling range. On the other hand, the amounts of water molecules and the
      behavior of the GM1, GD1a and GD1b micelles in the heating-and-cooling process
      greatly depended on the number of sialic acid residues in the sugar chain, that
      is, the penetration of water molecules was much more reversible for the GM1
      micelle compared with those for the GD1a and GD1b micelles. The observed clear
      hysteresis and the hydration characteristics of GD1 gangliosides would relate to
      their role in neuronal membranes, where GD1 gangliosides show the greatest
      concentrations.

PMID- 12046899
TI  - Cation diffusion in cartilage measured by pulsed field gradient NMR.
AB  - In this study, the pulsed field gradient (PFG) nuclear magnetic resonance (NMR)
      technique was used for the investigation of (1) concentration and compression
      effects on cation self-diffusion, and (2) restricted diffusion of cations in
      cartilage. Since physiologically relevant cations like Na+ are difficult to
      investigate owing to their very short relaxation times, the cations
      tetramethylammonium (TMA) and tetraethylammonium (TEA) were employed for
      diffusion studies in samples of explanted cartilage. Results indicated that the
      diffusion of monovalent cations shows strong similarities to observations already
      made in studies of the diffusion of water in cartilage: with increasing
      compression, i.e. decreasing water content, the diffusion coefficient of the
      cation decreases concomitantly. The diffusion coefficients also showed a decrease
      with increasing cation concentrations, basically reflecting the corresponding
      decrease in the water content. Both results could be explained by the well
      established model of Mackie and Meares. This, together with the similarity of the
      diffusion coefficient D in cartilage relative to free solution (about 50%) for
      both cations, is consistent with the view that the water content and not the
      charge is the most important determinant of the intratissue diffusivity of
      monovalent cations. Diffusion studies with increasing observation times showed
      strong evidence of restricted diffusion, allowing the estimation of the geometry
      of barriers within cartilage.

PMID- 12046900
TI  - Site-specific tryptophan fluorescence spectroscopy as a probe of membrane peptide
      structure and dynamics.
AB  - The fluorescence from tryptophan contains valuable information about the
      environment local to the indole side-chain. This environment sensitivity coupled
      with the ability to synthetically or genetically incorporate a single tryptophan
      residue at specific sites in a polypeptide sequence has provided the membrane
      biophysicist with powerful tools for examining the structure and dynamics of
      membrane peptides and proteins. Here we briefly review the use of site-specific
      tryptophan fluorescence spectroscopy to probe aspects of peptide orientation,
      structure, and dynamics in lipid bilayers, focusing on recent developments in the
      literature.

PMID- 12046901
TI  - Financing children's health care.

PMID- 12046902
TI  - Radiologic case study. Giant-cell tumor of the wrist in a skeletally immature
      girl.

PMID- 12046903
TI  - Mini-incisions: two for the price of one!

PMID- 12046904
TI  - Mini-incisions: visualization is key.

PMID- 12046905
TI  - Utilitarian shoulder approach for malignant tumor resection.
AB  - Malignant tumors involving the shoulder girdle can arise from four distinct
      locations: the proximal humerus, scapula, periscapular muscles, and axillary
      structures. This article describes a utilitarian shoulder approach that can be
      used to resect these tumors.

PMID- 12046906
TI  - Vascularized muscle pedicle flap for osteonecrosis of the femoral head.
AB  - Osteonecrosis is a devastating, locally progressive degenerative condition that
      mainly affects young adults. Osteonecrosis of the femoral head requires
      biological hip reconstruction. This article describes a technique that uses a
      vascularized muscle pedicle flap as a viable bone graft for treatment of this
      condition.

PMID- 12046907
TI  - Atrophy of semitzendinosus and gracilis and flexor mechanism function after
      hamstring tendon harvest for anterior cruciate ligament reconstruction.
AB  - The cross-sectional areas of individual knee flexors and isokinetic flexion
      measurements were evaluated using computed tomography in 13 patients following
      semitendinosus and gracilis tendon harvest for anterior cruciate ligament
      reconstruction. The atrophy of tendon-dissected muscles demonstrated variance
      with two peaks: >70% and <50%. In three patients whose semitendinosus and
      gracilis muscles displayed areas <50% of the contralateral area, the cross
      sectional area of the entire flexor group and work at >75 degrees of knee flexion
      was 88.1% and 51.9%, respectively. Therefore, hamstring tendon harvest can induce
      atrophy of tendon-dissected muscles and decrease flexor function.

PMID- 12046908
TI  - The impact of mixed components on polyethylene wear.
AB  - Wear rates were measured in 50 mixed and 71 matched total hip arthroplasties with
      > or = 3-year follow-up to determine whether implanting mixed hip components
      increased polyethylene wear. Average patient age was 61 years for the mixed group
      and 57 years for the matched group. Average radiographic follow-up was 5.8 years
      and 6.8 years, respectively. The average linear wear rate for the mixed and
      matched groups was 0.11 mm/y. Therefore, implanting same-size, total hip
      components from different manufacturers did not lead to large increases in
      polyethylene wear.

PMID- 12046909
TI  - Photoelastic and thermoelastic measurement of stress on the proximal femur before
      and after implantation of a hip prosthesis with retention of the femoral neck.
AB  - This study demonstrated the improved medial support and the transfer of load onto
      the retained neck of the femur using seven fresh frozen femurs. Results confirm
      the reliability of the thermoelastic stress analysis method, which is comparable
      to the photoelastic surface coating method, but with greater sensitivity. The
      loading pattern after stem implantation shows a homogeneous transfer of force
      onto the preserved femoral neck. After femoral neck removal, an inhomogeneous
      increase of the intertrochanteric compression loading was observed. Therefore,
      improved biomechanical conditions are created for a permanently stable
      implantation of stem prostheses with retention of the femoral neck.

PMID- 12046910
TI  - The role of proximal femoral valgus osteotomy in Legg-Calve-Perthes disease.
AB  - Proximal femoral valgus osteotomy for Legg-Calve-Perthes disease was evaluated at
      an average 5 years postoperatively in 31 consecutive patients. The indications
      for osteotomy were hinge abduction and pain. The Iowa hip scores at follow-up for
      21 patients averaged 93 points. Combined clinical and radiographic review for
      these patients yielded 6 (29%) excellent, 7 (33%) good, 5 (24%) fair, and 3 (14%)
      poor results. The 10 remaining patients had good pain relief and were satisfied
      but were unable to return for hip scale evaluation.

PMID- 12046911
TI  - Phalen's test with carpal compression: testing in diabetics for the diagnosis of
      carpal tunnel syndrome.
AB  - Phalen's test with carpal compression is a reliable clinical test for the
      diagnosis of carpal tunnel syndrome. Along with classical clinical symptoms and
      positive clinical tests there may be no need to perform additonal
      electrodiagnostic studies, thus saving time and money. However, in the diabetic
      population this test has been shown to be a less reliable clinical tool in the
      diagnosis of carpal tunnel syndrome. Therefore, Phalen's test with carpal
      compression is not a predictive indicator of carpal tunnel syndrome in the
      diabetic population.

PMID- 12046912
TI  - The effects of dynamization and destabilization of the external fixator on
      fracture healing: a comparative biomechanical study in dogs.
AB  - This study compared the effects of axial dynamization and staged destabilization
      on fracture healing. Bilateral midshafts of canine tibiae were osteotomized and
      fixed with an external fixator. The hind limbs were divided into two groups: the
      destabilized group in which the fixator's stiffness was progressively reduced
      over time and the axially dynamized group in which the fixator was axially
      dynamized. The healed tibiae were tested for 3-point bending in the
      anteroposterior plane. The biomechanical tests performed 2 months postoperatively
      revealed that the side with the destabilized fixator was more rigid than the side
      with the axially dynamized fixator, but the differences were insignificant
      (P=.20). This study showed staged destabilization of the fixator's stiffness was
      as effective on the enhancement of fracture healing as axial dynamization.

PMID- 12046913
TI  - Comparison of posteromedial and subtalar release in surgical treatment of
      resistant clubfoot.
AB  - This preliminary study evalluated two surgical techniques for the treatment of
      resistant clubfoot: the posteromedial and the subtalar release. Two groups of
      matched patients with idiopathic clubfoot who underwent surgery between 1983 and
      1995 were compared. In group 1 (12 patients, 18 feet), posteromedial release was
      performed. In this group, the results were satisfactory with a tendency to
      hypocorrection: 4 (22%) feet needed a secondary procedure (average follow-up:
      97.8 months). Group 2 (12 patients, 17 feet) underwent complete subtalar release.
      The results were clinically better for group 2 (average follow-up: 38.8 months).
      Only 1 (5.9%) patient needed a secondary procedure. These results suggest
      complete subtalar release yields better postoperative correction than
      posteromedial release.

PMID- 12046915
TI  - Posterior dislocation of a semiconstrained total knee prosthesis.

PMID- 12046914
TI  - Thrombosis of the greater saphenous vein in a collegiate football place kicker.
AB  - The greater saphenous vein is vulnerable in its superficial course overlying the
      distal tibia in the zone of impact of a kicker's foot. Minor repetitive trauma or
      a single traumatic event to this area may subject the vein to intimal trauma or
      other irregularities that may lead to vein thrombosis.

PMID- 12046916
TI  - Surgical treatment of ipsilateral pathologic femoral lesions with a proximal
      femoral replacement intramedullary rod construct.

PMID- 12046917
TI  - Isolated knee joint infection with Neisseria meningitidis.

PMID- 12046918
TI  - Protein-c deficiency in a patient with Legg-Calve-Perthes disease and recurrent
      deep vein thrombosis.

PMID- 12046919
TI  - Metal chelating properties of pyridine-2,6-bis(thiocarboxylic acid) produced by
      Pseudomonas spp. and the biological activities of the formed complexes.
AB  - We evaluated the ability of pyridine-2,6-bis(thiocarboxylic acid) (pdtc) to form
      complexes with 19 metals and 3 metalloids. Pdtc formed complexes with 14 of the
      metals. Two of these metal:pdtc complexes, Co:(pdtc)2 and Cu:pdtc, showed the
      ability to cycle between redox states, bringing to 4 the number of known redox
      active pdtc complexes. A precipitant formed when pdtc was added to solutions of
      As, Cd, Hg, Mn, Pb, and Se. Additionally, 14 of 16 microbial strains tested were
      protected from Hg toxicity when pdtc was present. Pdtc also mediated protection
      from the toxic effects of Cd and Te, but for fewer strains. Pdtc by itself does
      not facilitate iron uptake, but increases the overall level of iron uptake of
      Pseudomonas stutzeri strain KC and P. putida DSM301. Both these pseudomonads
      could reduce amorphous Fe(III) oxyhydroxide in culture. In vitro reactions showed
      that copper and pdtc were required for this activity. This reaction may derive
      its reducing power from the hydrolysis of the thiocarboxyl groups of pdtc.

PMID- 12046920
TI  - Ferric hydroxamate binding protein FhuD from Escherichia coli: mutants in
      conserved and non-conserved regions.
AB  - Uptake of iron complexes into the gram-negative bacterial cell requires highly
      specific outer membrane receptors and specific ATP-dependent (ATP-Binding
      Cassette (ABC)) transport systems located in the inner membrane. The latter type
      of import system is characterized by a periplasmic binding protein (BP), integral
      membrane proteins, and membrane-associated ATP-hydrolyzing proteins. In gram
      positive bacteria lacking the periplasmic space, the binding proteins are
      lipoproteins tethered to the cytoplasmic membrane. To date, there is little
      structural information about the components of ABC transport systems involved in
      iron complex transport. The recently determined structure of the Escherichia coli
      periplasmic ferric siderophore binding protein FhuD is unique for an ABC
      transport system (Clarke et al. 2000). Unlike other BP's, FhuD has two domains
      connected by a long alpha-helix. The ligand binds in a shallow pocket between the
      two domains. In vivo and in vitro analysis of single amino acid mutants of FhuD
      identified several residues that are important for proper functioning of the
      protein. In this study, the mutated residues were mapped to the protein structure
      to define special areas and specific amino acid residues in E. coli FhuD that are
      vital for correct protein function. A number of these important residues were
      localized in conserved regions according to a multiple sequence alignment of E.
      coli FhuD with other BP's that transport siderophores, heme, and vitamin B12. The
      alignment and structure prediction of these polypeptides indicate that they form
      a distinct family of periplasmic binding proteins.

PMID- 12046921
TI  - New synthetic catecholate-type siderophores with triamine backbone.
AB  - New analogues of triscatecholate siderophores based on linear or tripodal
      triamines with or without spacer groups or lipophilic and hydrophilic
      substituents were synthesized. The catecholate moieties were prepared in OH
      forms, as acetylated compounds or masked as 8-methoxycarbonyloxy-2,4-dioxo-1,3
      benzoxazine derivatives. Some of the new compounds were active as siderophores
      tested by growth promotion assays using various gram-negative bacteria and
      mycobacteria under iron limitation and by CAS-assay. Structure-activity
      correlations have been studied.

PMID- 12046922
TI  - Characterization of cadmium- and lead-phytochelatin complexes formed in a marine
      microalga in response to metal exposure.
AB  - Phytochelatins (PCn) are thiol-containing peptides with general structure (gamma
      Glu-Cys)n-Gly enzymatically synthesized by plants and algae in response to metal
      exposure. They are involved in the cellular detoxification mechanism for their
      capability to form stable metal-phytochelatin complexes. The speciation of Cd and
      Pb complexes with phytochelatins has been studied in laboratory cultures of the
      marine diatom Phaeodactylum tricornutum. An approach based on size-exclusion
      chromatography (SEC) with off-line detection of phytochelatins, by reverse-phase
      HPLC, and metal ion, by atomic absorption spectrometry, has been used. The
      formation of Cd- and Pb-PCn complexes with n-value from 3 to 6 was demonstrated.
      The metal-PCn complexes formed with Cd appear to be different from those formed
      with Pb for the number of molecules of peptide involved in the complex and for
      the amount of the metal ion bound. The chromatographic behaviour of metal-PCn
      complexes is consistent with Pb-PCn complexes in which only a molecule of peptide
      binds the metal ion, and with Cd-PCn complexes containing two or more molecules
      of peptide. The metal/peptide molar ratio in Cd-PCn complexes was higher that in
      Pb-PCn complexes. The formation of Cd- or Pb-PC2 complexes was not demonstrated,
      probably for a dissociation during the cellular extract preparation. The
      effectiveness of phytochelatins in the detoxification of these two metal ions in
      this alga is discussed.

PMID- 12046923
TI  - Bisucaberin--a dihydroxamate siderophore isolated from Vibrio salmonicida, an
      important pathogen of farmed Atlantic salmon (Salmo salar).
AB  - A siderophore of the bacterial fish pathogen, Vibrio salmonicida, was isolated
      from low-iron culture supernatant and structurally characterized as bisucaberin
      by FTICR- and FAB-MS, NMR and GC-MS analysis of the hydrolysis products. Although
      the cyclic dihydroxamate bisucaberin has previously been isolated from a marine
      bacterium, Alteromonas haloplanktis, its involvement in cold-water vibriosis of
      Atlantic salmon (Salmon salar) is novel. Bisucaberin production in iron-limited
      media was highest at temperatures around and below 10 degrees C, correlating well
      with temperatures at which outbreaks of cold-water vibriosis occur. Due to the
      very high stability constant of K = 32.2, bisucaberin is a most efficient iron
      scavenger which may contribute to the virulence of V. salmonicida in Atlantic
      salmon.

PMID- 12046924
TI  - Characterization of autoantibodies to ferritin in canine serum.
AB  - Ferritin-binding proteins circulating in mammalian blood are thought to be
      involved in the clearance of ferritin. The present study characterizes canine
      serum autoantibodies (IgM and IgA) that react with ferritin. Canine IgM and IgA
      bound to bovine spleen ferritin as well as canine liver ferritin. To examine the
      specificity of canine IgM and IgA to ferritin H and L subunits, we used canine
      heart ferritin and canine liver ferritin with H/L subunit ratios of 3.69 and
      0.43, respectively. Canine IgM and IgA recognized both of the H- and L-subunit
      rich isoferritins, showing that their binding activities to ferritin depend on
      the H-subunit content. Recombinant bovine H-chain ferritin homopolymer expressed
      in a baculovirus expression system bound more with IgM and IgA than the
      recombinant L-chain homopolymer expressed under the same conditions. These
      results suggest that canine IgM and IgA recognize H-subunit-rich isoferritins,
      and that H-subunit-rich isoferritins are cleared from the circulation more
      rapidly than L-subunit-rich isoferritins.

PMID- 12046925
TI  - The extremely high Al resistance of Penicillium janthineleum F-13 is not caused
      by internal or external sequestration of Al.
AB  - Penicillium janthinellum F-13 has been isolated in previous work as a fungus
      tolerating the presence of high concentrations of Al (as high as 100 mM AlCl3).
      Here its growth rate and yield in three acidic (pH 3.0) media of different
      composition with varying concentrations of Al are reported. The presence of Al
      did not affect these parameters. except that the growth yield was somewhat lower
      in GM (a glucose/peptone/yeast extract-containing medium) with the highest
      concentration tested (100 mM AlCl3). The amount of Al found in the mycelium was
      so low that it cannot lead to a significant decrease in the medium for the higher
      Al concentrations applied. Although citric acid was excreted at growth on GM, and
      the presence of Al even promoted this, the concentration of this was far too low
      to diminish (by chelation) the high Al concentrations in the medium to a non
      toxic level, i.e. the level (of approx. 1 mM) that is tolerated by low-resistance
      fungi. At growth on SLBM (a peptone/yeast extract/soil extract-containing
      medium), a rise in pH occurred. The same was found for SM (a glucose/mineral
      salts-containing medium), although in this case the picture was more complicated
      because the initial rise in pH was followed by a lowering due to the excretion of
      oxalic acid. Although both phenomena can diminish Al toxicity (by decreasing the
      external concentration of monomeric Al, regarded to be the toxic species), again
      the decrease is far too low to attain a non-toxic level when high Al
      concentrations are applied. Therefore, although in principal the metabolic
      phenomena observed for P. janthinellum F-13 at growth on different media can
      diminish Al toxicity, the tolerance of this organism for high external Al
      concentrations must be caused by another mechanism.

PMID- 12046926
TI  - Effect of dietary calcium on cadmium absorption and retention in suckling rats.
AB  - The effect of calcium supplementation on absorption and retention of cadmium in
      the suckling period was evaluated in Wistar rat pups of both sexes. Animals were
      maintained in the litters with the mother rats and supplemented with 1%, 3% or 6%
      calcium (as CaHPO4 x 2H2O) in cow's milk by artificial feeding from day of birth
      6 through 14. All rats were exposed to cadmium (as CdCl2 x H2O) either orally or
      parenterally. Oral cadmium dose of 0.5 mg/kg body weight a day was administered
      through nine-day period of calcium supplementation and parenteral cadmium dose
      was injected subcutaneously in a single dose of 0.5 mg Cd/kg body weight prior to
      calcium supplementation. On experimental day 10 (at the age of pups of 15 days)
      all animals were killed and the liver, kidneys, brain and carcass (body without
      organs and skin) were removed for element analyses. Cadmium and essential
      elements calcium, zinc and iron were analysed in the tissues by atomic absorption
      spectrometry. Results showed that after oral exposure cadmium concentrations in
      all calcium-supplemented groups were significantly decreased in the organs and
      carcass and that the effect was dose-related. No such effect of calcium was found
      after parenteral cadmium exposure. Calcium supplementation per se significantly
      increased calcium concentration in the carcass and had no effect on iron in
      organs and zinc in carcass. It was concluded that calcium supplementation during
      the suckling period could be an efficient way of reducing oral cadmium absorption
      and retention without affecting tissue essential trace element concentrations.

PMID- 12046927
TI  - Possible role of glutamate, aspartate, glutamine, GABA or taurine on cadmium
      toxicity on the hypothalamic pituitary axis activity in adult male rats.
AB  - This work was designed to evaluate the possible changes in glutamate, aspartate,
      glutamine, GABA and taurine within various hypothalamic areas the striatum and
      prefrontal cortex after oral cadmium exposure in adult male rats, and if these
      changes are related to pituitary hormone secretion. The contents of glutamine,
      glutamate, aspartate, GABA and taurine in the median eminence, anterior,
      mediobasal and posterior hypothalamus, and in prefrontal cortex in adult male
      rats exposed to 272.7 micromol l(-1) of cadmium chloride (CdCl2) in the drinking
      water for one month. Cadmium diminished the content of glutamine, glutamate and
      aspartate in anterior hypothalamus as compared to the values found in the
      untreated group. Besides, there is a decrease in the content of glutamate,
      aspartate and taurine in the prefrontal cortex. The amino acids studied did not
      change in median eminence, mediobasal and posterior hypothalamus or the striatum
      by cadmium treatment. Plasma prolactin and LH levels decreased in rats exposed to
      the metal. These results suggest that (1) cadmium differentially affects amino
      acid content within the brain region studied and (2) the inhibitory effect of
      cadmium on prolactin and LH secretion may be partially explained by a decrease in
      the content of both glutamate and aspartate in anterior hypothalamus, but not
      through changes in GABA and taurine.

PMID- 12046928
TI  - Relationship between mercury concentration in blood, cognitive performance, and
      blood pressure, in an elderly urban population.
AB  - Concentration of mercury (Hg) in whole blood in an elderly urban population with
      a mean age of 87 years was studied in relation to cognitive function, arterial
      blood pressure (arterial BP), age, gender, body mass index (BMI) and smoking
      habits. This population-based study consisted of 106 subjects both males and
      females. Clinical assessment of the subjects included medical and social history,
      physical and neurologic examination and assessment of cognitive functions with
      Mini-Mental State Examination (MMSE). Information on use of all potentially
      antihypertensive drugs was collected. Whole blood from 106 subjects were
      collected and analysed for mercury by Cold Vapour Atomic Absorption Spectrometry
      (Milton Ray ASS-CV) with Seronorm Trace Element as matrix matched quality
      control. Males and females did not differ in blood-mercury (B-Hg) concentrations
      or in any of the other studied variables. B-Hg concentrations did not differ
      between smokers and non-smokers. Females were treated more often than males with
      antihypertensive drugs. There was no relation found between B-Hg concentration
      and cognitive function, arterial BP, age, gender or BMI. In conclusion, no
      relations were found between B-Hg concentrations and the studied variables.

PMID- 12046929
TI  - Estimation and reduction of decorrelation effect due to tissue lateral
      displacement in elastography.
AB  - In cross-correlation based elastography, the quality of the strain image is
      degraded by the distortion of echo waveforms due to tissue axial and lateral
      displacement. To study the effects of tissue lateral displacement on echo
      decorrelation, a tissue axial stretching model is developed and a concept called
      correlation signal-to-noise ratio (CSNR) is introduced to quantify the
      decorrelation effect due to tissue lateral displacement. A computer simulation
      based on the tissue stretching model is carried out to study the influence of
      several important elastographic parameters on echo decorrelation due to tissue
      lateral displacement. Finally, guided by the CSNR concept, a 2-dimensional (D)
      spatial comprehensive cross-correlation method is proposed to reduce the
      decorrelation noise. Results indicate that CSNR can be used as a quality
      indicator of elastography and the 2-D spatial comprehensive cross-correlation
      method can effectively reduce the decorrelation noise while slightly decreasing
      the lateral resolution of the strain image.

PMID- 12046930
TI  - Quantitative imaging of Rayleigh wave velocity with a scanning acoustic
      microscope.
AB  - An acoustic microscope operating with impulse excitation has been used to perform
      measurements of the Rayleigh wave velocity by measuring the time difference
      between the direct reflected signal and the Rayleigh wave signal. The accuracy
      and precision of the methodology have been examined by performing measurements at
      a single location on an elastically isotropic sample of E6 glass. The accuracy of
      the Rayleigh wave velocity measurement has been determined to be better than
      0.5%. The measured Rayleigh wave velocity of (3035+/-5) m/s differs by 0.3% from
      measurements reported in the literature for a similar sample, using two different
      techniques. The methodology has been extended to acquire the Rayleigh wave
      velocity while raster scanning the sample to develop a quantitative velocity
      image. The background noise in the Rayleigh wave velocity image has been
      investigated by mapping the velocity on elastically isotropic E6 glass. Possible
      reasons for background noise in the images is discussed. The methodology has been
      extended to acquire quantitative Rayleigh wave velocity images on Ti-6Al-4V. The
      contrast in the images is attributed to the variation of the Rayleigh wave
      velocity in individual grains or regions. Applicability of the technique to
      investigate crystallographic texture in materials is discussed.

PMID- 12046931
TI  - Linear scanning array with bulk ferroelectric-integrated feed network.
AB  - Variable ferroelectric delay line technology has been utilized to implement a
      proof-of-concept, continuous scanning, ferroelectric integrated phased array
      antenna system. S21 phase shifts of up to 157 degrees have been achieved from the
      phase shifter itself via analogous variation of a DC bias. When integrated into a
      phased array, beam scanning of at least +/-12 degrees is achieved prior to any
      optimization. Some of the key material requirements, fabrication procedures,
      characterization, and assembly of the ferroelectric material will be revealed.
      The design, integration, and performance of the array system using such phased
      shifters will be presented.

PMID- 12046932
TI  - A theoretical assessment of a thermal technique to measure acoustic power
      radiated by ultrasound transducers.
AB  - The parameters affecting the temperature rise in an insonified absorber are
      studied computationally. Finite-element and analytical solutions are obtained for
      the transient energy equation in a cylindrical absorber. When the ultrasound beam
      radius is less than the radius of the absorber, the temperature field is seen to
      be considerably more complex than when the absorber cross section is uniformly
      heated. Circumstances in which power predictions based upon uniform heating would
      result in appreciable error are identified. The rise time required to achieve
      equilibrium is studied as a function of operational parameters, including
      absorber geometry and thermal properties as well as ultrasound beamwidth and
      frequency. The rise time is seen to increase approximately as the square of the
      absorber length, while optimized temperature rise increases linearly with
      absorber length, demonstrating a tradeoff in ultrasound power determination via
      equilibrium temperature measurements: longer lengths produce higher sensitivity,
      but also longer times before measurements can be made. A transient technique that
      may bypass this tradeoff is suggested.

PMID- 12046933
TI  - Piezoelectrically actuated flextensional micromachined ultrasound transducers--I:
      theory.
AB  - This series of two papers considers piezoelectrically actuated flextensional
      micromachined ultrasound transducers (PAFMUTs) and consists of theory,
      fabrication, and experimental parts. The theory presented in this paper is
      developed for an ultrasound transducer application presented in the second part.
      In the absence of analytical expressions for the equivalent circuit parameters of
      a flextensional transducer, it is difficult to calculate its optimal parameters
      and dimensions and difficult to choose suitable materials. The influence of
      coupling between flexural and extensional deformation and that of coupling
      between the structure and the acoustic volume on the dynamic response of
      piezoelectrically actuated flextensional transducer are analyzed using two
      analytical methods: classical thin (Kirchhoff) plate theory and Mindlin plate
      theory. Classical thin plate theory and Mindlin plate theory are applied to
      derive two-dimensional plate equations for the transducer and to calculate the
      coupled electromechanical field variables such as mechanical displacement and
      electrical input impedance. In these methods, the variations across the thickness
      direction vanish by using the bending moments per unit length or stress
      resultants. Thus, two-dimensional plate equations for a step-wise laminated
      circular plate are obtained as well as two different solutions to the
      corresponding systems. An equivalent circuit of the transducer is also obtained
      from these solutions.

PMID- 12046934
TI  - Piezoelectrically actuated flextensional micromachined ultrasound transducers-
      II: fabrication and experiments.
AB  - This paper presents novel micromachined two-dimensional array piezoelectrically
      actuated flextensional transducers that can be used to generate sound in air or
      water. Micromachining techniques to fabricate these devices are also presented.
      Individual unimorph array elements consist of a thin piezoelectric annular disk
      and a thin, fully clamped, circular plate. We manufacture the transducer in two
      dimensional arrays using planar silicon micromachining and demonstrate ultrasound
      transmission in air at 2.85 MHz with 0.15 microm/V peak displacement. The devices
      have a range of operating resonance frequencies starting from 450 kHz to 4.5 MHz.
      Such an array could be combined with on-board driving and addressing circuitry
      for different applications.

PMID- 12046935
TI  - SH wave propagation in piezoelectric coupled plates.
AB  - The propagation of shear horizontal (SH) wave in a piezoelectric coupled plate is
      investigated in this paper. Full account is taken of the piezoelectric coupling
      effect to the isotropic metal core in the mathematical model. One of the
      applications of this research is in the damage detection of the host metal
      structure from the wave propagation signal excited by the piezoelectric layer
      which is surface bonded on the surface of a metal core. This research is distinct
      from the previous works on SH propagation in piezoelectric structures because the
      piezoelectric materials were used as the core structure in the previous studies,
      and the potential of the studies was mainly on time-delay devices. The dispersive
      characteristics and the mode shapes of the transverse displacement and the
      electric potential of the piezoelectric layer are theoretically derived. The
      results from numerical simulations show that the phase velocity of the plate
      structure tends to the bulk shear wave velocity of the host metal core at high
      wavenumber when the shear wave velocity of host plate is larger than that of PZT
      bonded on it. Furthermore, there are three asymptotic solutions of wave
      propagation when the shear wave velocity of the host plate is smaller than that
      of PZT. The mode shape of the electric potential of the piezoelectric layer
      changes from the quadratic shape at lower wavenumber and with thinner
      piezoelectric layer to the shape with more zero nodes at higher wavenumber and
      with thicker piezoelectric layer. These findings are significant in the
      application of wave propagation in piezoelectric coupled structures.

PMID- 12046936
TI  - Effects of a liquid layer on thickness-shear vibrations of rectangular AT-cut
      quartz plates.
AB  - Thickness-shear vibrations of a rectangular AT-cut quartz with one face in
      contact with a layer of Newtonian (linearly viscous and compressible) fluid are
      studied. The two-dimensional (2-D) governing equations for vibrations of
      piezoelectric crystal plates given previously are used in the present study. The
      solutions for 1-D shear wave and compressional wave in a liquid layer are
      obtained, and the stresses at the bottom of the liquid layer are used as
      approximations to the stresses exerting on the crystal surface in the plate
      equations. Closed form solutions are obtained for both free and piezoelectrically
      forced thickness-shear vibrations of a finite, rectangular AT-cut quartz in
      contact with a liquid layer of finite thickness. From the present solutions, a
      simple and explicit formula is deduced for the resonance frequency of the
      fundamental thickness-shear mode, which includes the effects of both shear and
      compressional waves in the liquid layer and the effect of the thickness-to-length
      ratio of the crystal plate. The formula reduces to the widely used frequency
      equation obtained by many previous investigators for infinite plates. The
      resonance frequency of a rectangular AT-cut quartz, computed as a function of the
      thickness of the adjacent liquid layer, agrees closely with the experimental data
      measured by Schneider and Martin.

PMID- 12046937
TI  - Mechanical effects of electrodes on the vibrations of quartz crystal plates.
AB  - A system of approximate first-order equations is extracted from an infinite
      system of 2-D equations for piezoelectric crystal plates with thickness-graded
      material properties, which is deduced from the 3-D equations of linear
      piezoelectricity. These equations are used to study mechanical effects on the
      thickness-shear (TS), flexural (F), and face-shear (FS) vibrations of an AT-cut
      quartz plated with two identical electrodes. Dispersion curves are calculated
      from the present 2-D equations as well as the 3-D equations. The comparison of
      these curves shows that the agreement is very close for all three frequency
      branches of TS, F, and FS modes in a range up to the 1.5 times the fundamental TS
      frequency and for gold and aluminum electrodes with R, the ratio of the mass of
      the electrodes to that of the plate, equal to 0.05. without introducing any
      correction factors. In order to assess electrode effects, spectra of omega vs.
      a/bq (length-to-thickness ratio of the quartz) are computed for plates with gold
      and aluminum electrodes and different R ratios. And the spectrum of omega vs. R
      is computed for plates with aluminum electrodes and a given a/bq ratio. For a
      plate with gold electrodes, the frequencies of predominant TS, F, and FS modes
      are decreasing as R increases, but the amount of frequency changes for the TS
      mode is much greater than those for the other two modes. However, for a plate
      with aluminum electrodes, the frequencies of the TS and FS modes are decreasing,
      but those of the F modes are increasing as R increases.

PMID- 12046938
TI  - Cylindrical PVDF film transmitters and receivers for air ultrasound.
AB  - Cylindrical polyvinylidene fluoride (PVDF) film transducers for transmission and
      reception of 40-kHz ultrasonic waves in air have been investigated. A key feature
      of such transducers is their omni-directional polar response. An optimized
      structure comprises a cylindrical PVDF film element resting on a spool without a
      mechanical bond to it. Various key design equations to obtain the required
      ultrasonic performance both as transmitter and receiver are shown, which include
      resonance frequency, acoustic pressure, angle performance, back air cavity
      effect, and receiver sensitivity. Measurements of actual frequency response of
      transmitter output and receiver sensitivity, angular performance, back air space
      effect, and temperature effect are presented. The results agree well with the
      theoretical predictions. It has been shown that this device is well-suited for
      practical application as an ultrasonic ranging device.

PMID- 12046939
TI  - Fast variation method for elastic strip calculation.
AB  - A new, fast, variation method (FVM) for determining an elastic strip response to
      stresses arbitrarily distributed on the flat side of the strip is proposed. The
      remaining surface of the strip may have an arbitrary form, and it is free of
      stresses. The FVM, as well as the well-known finite element method (FEM), starts
      with the variational principle. However, it does not use the meshing of the
      strip. A comparison of FVM results with the exact analytical solution in the
      special case of shear stresses and a rectangular strip demonstrates an excellent
      agreement.

PMID- 12046940
TI  - Measurement of static and vibration-induced phase noise in UHF thin-film
      resonator (TFR) filters.
AB  - Measurements of the static phase noise and vibration sensitivity of thin-film
      resonator (TFR) filters operating at 640 and 2110 MHz have been made. They show
      that the short-term frequency instability of the filters is small compared with
      that induced in the oscillator signal by the sustaining stage amplifier PM (phase
      modulation) noise. In-oscillator measurement of filter performance under
      vibration indicates that fractional frequency vibration sensitivities
      (deltafo/fo) are on the order of several parts in 10(-9)/g. Because the
      percentage bandwidth and order (number of poles) of the filters was fairly
      constant, so was the product of the center frequency and group delay. Thus, the
      fractional frequency vibration sensitivity of the filters can be expressed
      alternatively as carrier signal phase sensitivity to vibration. The tau-omega0
      product for the filters that were tested was on the order of 300 rad, so that the
      equivalent phase sensitivity to vibration was approximately 1 microrad/g.

PMID- 12046941
TI  - Surface-related phase noise in SAW resonators.
AB  - With the advent of nanotechnologies, electronic devices are shrinking in
      thickness and width to reduce mass and, thereby, increase frequency and spe
      Lithographic approaches are capable of creating metal connections with thickness
      and lateral dimensions down to about 20 nm, approaching the molecular scale. As a
      result, the dimensions of outer particles are comparable with, or even larger
      than, those of active or passive regions in electronics devices. Therefore,
      directing our attention toward the effect of surface fluctuations is of practical
      significance. In fact, electronic device surface-related phenomena have already
      received more and more attention as device size decreases. In connection with
      surface phase noise, selection of a suitable device with high surface sensitivity
      is important. In this paper, high Q-value surface acoustic wave resonators were
      employed because of their strong sensitivity to surface perturbation. Phase noise
      in SAW resonators related to surface particle motion has been examined both
      theoretically and experimentally. This kind of noise has been studied from the
      point of view of a stochastic process resulting from particle molecular
      adsorption and desorption. Experimental results suggest that some volatile vapors
      can change flicker noise 1/f and random walk noise 1/f2. An analysis has been
      made indicating that these effects are not associated with Q value variation, but
      are generated by the change in the dynamic rate of adsorption and desorption of
      surface particles. Research on particle motion above the device substrate might
      explain the differences observed from the model based only on the substrate
      itself. Results might lead to a better understanding of the phase noise mechanism
      in micro-electronic devices and help us to build oscillators with improved
      performance.

PMID- 12046942
TI  - BAW temperature sensitivity and coupling in langanite.
AB  - One of the new materials belonging to the trigonal class 32, to which quartz
      belongs, is langanite (LGN, La3Ga5.5Nb0.5O14). High-quality LGN single crystals
      are now available, and, although similar in composition and structure to
      langasite (LGS, La3Ga5SiO14), LGN has smaller thermal expansion coefficients and
      comparable piezoelectric constants to LGS. These are desirable material
      properties for both SAW and BAW applications that require low frequency
      dependence on temperature. This paper examines in detail the LGN characteristics:
      phase velocity, temperature coefficient of frequency (TCF), electromechanical
      coupling coefficient, and power flow angle for both singly and doubly rotated
      plate cuts. Contour plots of these characteristics are constructed, revealing
      orientation regions where zero TCF and high coupling exist and suggesting
      potentially interesting cuts for practical BAW device design. Temperature
      compensated cut regions with coupling coefficients as high as 0.16 are predicted,
      which is twice the value for AT-cut quartz, along with a temperature compensated
      cut with cubic behavior around room temperature for one of the sets of material
      constants used. With such desirable properties, LGN is a promising candidate
      material for BAW applications requiring low temperature sensitivity with superior
      bandwidth characteristics due to its values of coupling coefficient larger than
      quartz. Several other orientations with low TCF and high coupling are also
      identified.

PMID- 12046943
TI  - Classification of ultrasonic B mode images of the breast using frequency
      diversity and Nakagami statistics.
AB  - The parameters of the Nakagami distribution have been utilized in the past to
      classify lesions in breast tissue as benign or malignant. To avoid the effect of
      operatorgain settings on the parameters of the Nakagami distribution, normalized
      parameters were utilized for the classification. The normalized parameter was
      defined as the ratio of the parameter at the site of the lesion to its average
      value over several regions away from the site. This technique, however, was very
      time consuming. In this paper, the application of frequency diversity and
      compounding is explored to achieve this normalization. Lesions are classified
      using these normalized parameters at the site. A receiver operating
      characteristic (ROC) analysis of the parameters of the Nakagami distribution has
      been conducted before and after compounding on a data set of 60 benign and 65
      malignant lesions. The ROC results indicate that this technique can reasonably
      classify lesions in breast tissue as benign or malignant.

PMID- 12046944
TI  - Characterization of MEMS transducer performance using near-field scanning
      interferometry.
AB  - Sophisticated ultrasonic transducer microarrays based on micro-electro-mechanical
      systems (MEMS) technologies are quickly becoming a reality. A current challenge
      for many researchers is characterizing the dynamic performance of these and other
      micro-mechanical devices. In this work, the performance characteristics of a MEMS
      ultrasonic transducer array were successfully measured using a scanning
      heterodyne interferometer system. The dynamic response of the entire transducer
      array was measured, and the results were compared with theoretical predictions.
      Individual elements were found to vibrate with Bessel-like displacement patterns,
      and they were resonant at approximately 4 MHz. The full array showed variations
      in peak out-of-plane displacement levels across the device of 16%, and isolated
      elements that were dramatically overresponsive and under-responsive. The measured
      variations across the array may have an undesirable impact on the performance of
      the transducer and its radiated field.

PMID- 12046945
TI  - Measurements of major ion concentration in settled coarse particles and aerosols
      at a semiarid rural site in India.
AB  - Deposition rates and deposition velocities of water-soluble ions (F, Cl, NO3,
      SO4, NH4, Ca, Mg, Na and K) were measured at a rural site (Gopalpura, Agra). Dry
      deposition samples were collected throughout the year from December 1995 to
      August 1997, while the aerosol samples were collected only during the winter
      season of 1996. Surrogate technique was used to collect the dry deposition
      samples, while aerosol samples were collected on PTFE membrane filter. Deposition
      velocities (Vd) of SO4 and NO3 are < or = 0.01 m s(-1) while Ca, Mg, Na, K, NH4,
      F and Cl exhibit greater than 0.01 m s(-1) Equivalent concentration ratios of
      K/Na, Ca/Na and Mg/Na conform with the corresponding ratios of local soil,
      indicating the dominant contribution of local sources. Deposition rates are
      maximum in winter, followed by summer and monsoon. No significant differences are
      found in dry deposition rates of all ions or in atmospheric concentrations of
      soil-derived elements with respect to wind direction. However, in aerosols,
      concentrations of F, Cl, NO3 and SO4 are higher with winds from southwesterly and
      westerly directions corresponding to pollution sources located in these
      directions. Deposition data have been used to calculate the critical load of S
      and N for soil with respect to Triticum vulgaris. The critical load of actual
      acidity was found to be 622.4 eq ha(-1) year(-1) within the range of 500-1,000 eq
      ha(-1) year(-1) as assessed by the RAINS-Asia model for this region. The present
      load of S and N (77.4 and 86.4 eq ha(-1) year(-1)) was much lower than the
      critical load of S and N (622.4 and 2,000 eq ha(-1) year(-1)), indicating that at
      present there is no harmful effect on ecosystem structure and function.

PMID- 12046946
TI  - Transfer of dioxin risk between nine major municipal waste incinerators in
      Taiwan.
AB  - The objective of this study was to assess site-specific carcinogenic risks of
      incinerator-emitted dioxins and risk transfers among the areas covered by nine
      municipal incinerators in Taiwan. We used actual emission data and the industrial
      source complex short-term model (ISCST3) to determine the dioxin impact areas
      within the 8 x 8-km simulation regions surrounding the incinerators. We then used
      multimedia model to estimate cancer risks in individual impact areas for two
      exposure scenarios, which were sufficient (SFP) and insufficient food production
      (IFP) for residents' consumption in each impact area. We also used information of
      food supply and consumption between impact areas to calculate risk transfers
      among these nine incinerators. We found that dioxins' carcinogenic risks ranged
      from 1.4 x 10(-8) (Incinerator F) to 7.1 x 10(-5) (Incinerator A) for the nine
      incinerators under the exposure scenario of SFP, and ranged from 8.7 x 10(-8)
      (Incinerator D) to 1.1 X 10(-6) (Incinerator E) under the exposure scenario of
      IFP. The food ingestion was the main exposure pathway, which accounted for 64-99%
      of total dioxin risks among nine impact areas. For the nine major food items
      consumed by residents in the impact areas, eggs (14-35%) and chicken (11-26%)
      were two main routes of dioxin exposure in the SFP scenario, while chicken (8
      78%) and vegetables (0.2-81%) were two main routes of dioxin exposure in the IFP
      scenario. Significant risks of dioxins were transferred among incinerators, which
      accounted for up to 88% among the incinerators. Incinerator E was the major risk
      exporting source to six Incinerators C, D, F, G, H, and I. For these six
      incinerators, Incinerator E accounted for their 51-88% imported risks. We
      concluded that risk transfers among incinerators through routes of food
      consumption should be considered in assessing health risks associated with
      incinerator-emitted dioxins in Taiwan. We should place high priority on
      implementing control measures to lower dioxin emissions in important food
      exporting areas like Incinerator E. We should also emphasize analyzing dioxin
      contents in eggs, chicken, and vegetables in order to improve dioxin-related
      health risk assessments in the future.

PMID- 12046947
TI  - Heavy metal concentrations in Squilla mantis (L.) (Crustacea, Stomatopoda) from
      the gulf of cadiz evaluation of the impact of the Aznalcollar mining spill.
AB  - After the Aznalcollar mining spill (25th April 1998), considerable social concern
      arose amongst the inhabitants of the SW Iberian Peninsula concerning the
      consumption of local seafood. Squilla mantis was collected in four regions of the
      Gulf of Cadiz with a dual objective: to analyze the heavy metal levels for human
      consumption and as part of biomonitoring program. Heavy metal concentrations (Fe,
      Mn, Zn, Cu, Cd and Pb) were analyzed in soft tissues and cuticle. The highest
      values were found in the soft tissues for zinc, copper and cadmium and in the
      cuticle for iron, manganese and lead. The mean copper concentration in the soft
      tissue, corresponding to the edible part, was 27.1 microg x g(-1) wet weight.
      Approximately 80% of stations showed values higher than 20 microg x g(-1) wet
      weight of copper, the Spanish legal limit for the concentration of this metal in
      the crustacean for human consumption. For Zn and Cu no significant differences
      were found between regions, probably related with the capacity for regulation of
      S. mantis. The highest values found for copper in the Gulf of Cadiz compared to
      other areas is likely to be related with contamination from terrestrial mining
      activities (copper and pyrites) in the region, dating back to the times of
      Tartessians and Romans, rather than the effects of mining spill which was shown
      not to create any significant increases in heavy metal concentrations of
      organisms of the Guadalquivir River or the adjacent coastal area.

PMID- 12046948
TI  - Correlations between speciation of Cd, Cu, Pb And Zn in sediment and their
      concentrations in total soft tissue of green-lipped mussel Perna viridis from the
      west coast of Peninsular Malaysia.
AB  - Total concentrations and speciation of cadmium (Cd), copper (Cu), lead (Pb) and
      zinc (Zn) in surface sediment samples were correlated with the respective metal
      measured in the total soft tissue of the green-lipped mussel Perna viridis,
      collected from water off the west coast of Peninsular Malaysia. The aim of this
      study is to relate the possible differences in the accumulation patterns of the
      heavy metals in P. viridis to those in the surface sediment. The sequential
      extraction technique was employed to fractionate the sediment into 'freely
      leachable and exchangeable' (EFLE), 'acid-reducible,' 'oxidisable-organic' and
      'resistant' fractions. The results showed that significant (P<.05) correlations
      were observed between Cd in P. viridis and Cd in the sediment (EFLE fraction and
      total Cd), Cu in P viridis and Cu in the sediment (EFLE and 'acid-reducible'
      fractions and total Cu) and Pb in P viridis and Pb in the sediment ('oxidisable
      organic' fraction and total Pb). No significant correlation (P > .05) was found
      between Zn in P viridis and all the sediment geochemical fractions of Zn and
      total Zn in the sediment. This indicated that Zn was possibly regulated from the
      soft tissue of P. viridis. The present results supported the use of P viridis as
      a suitable biomonitoring agent for Cd, Cu and Pb.

PMID- 12046949
TI  - Phytomonitoring the unique colonization of oil-contaminated saline environment by
      Limoniastrum monopetalum (L.) Boiss in Egypt.
AB  - A site that covers over 20 acres of coastal saline depression in the western
      Mediterranean coastal desert of Egypt (El-Hammra station, the main crude oil
      pipeline terminal in Al-Alamein) is contaminated with crude oil spill as a result
      of activities from refineries, oilfield blowouts, tanker and pipeline break-ups.
      This area, prior to contamination, was dominated by different common halophytes.
      However, Limoniastrum monopetalum is now the only species found growing in the
      oil-contaminated soil. A specific question addressed in the present study was:
      what are the biochemical changes occurring in a desert plant growing in oil
      contaminated soils? Major metabolites such as proline, betaine, free amino acids,
      fatty acid esters and mineral elements were studied. The plant samples were
      collected from the oil-contaminated, as well as noncontaminated, sites. The
      higher concentration in the selected organic metabolites in the plants growing in
      the contaminated site compared to those in noncontaminated site may be due to
      differences in a number of receptors. The sensitivity of such receptors for the
      environmental signal that cause differences in genetic expression leads to
      differences in physiological processes. The change in the landscape of the
      contaminated area and the elimination of the natural vegetation, except L.
      monopetalum, may explain the competitive balance toward the oil-resistant
      species.

PMID- 12046950
TI  - PCDD/F levels in the neighbourhood of a municipal solid waste incinerator after
      introduction of technical improvements in the facility.
AB  - In 1998 and 1999, the concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) were determined in soil and herbage samples collected in
      the vicinity of an old municipal solid waste incinerator (MSWI) (S. Adria del
      Besos, Barcelona, Spain). Just after the 1999 collection, an adaptation to the EU
      legislation on pollutant emissions from the stack was carried out in this
      facility. The purpose of the present study was to determine the current
      concentrations of PCDD/Fs in soil and herbage samples collected in the
      neighbourhood of the MSWI and to compare these concentrations with those obtained
      in the 1998 and 1999 surveys. During the period 1998-1999, an increase of 31%
      (P>.05) was found in the median PCDD/F levels in soils, while a reduction of 40%
      (P>.05) was observed in the period 1999-2000. Similarly, in the period 1998-1999
      an increase of 41% (P>.05) was found in the levels of PCDD/Fs in vegetation,
      while a 30% decrease (P<.05) was seen in the period 1999-2000. Although after
      introduction of the technical improvements in the MSWI a notable reduction in the
      levels of PCDD/Fs in soil and vegetation has been noted, the median decreases
      have not been as great as it could be expected according to the very pronounced
      reductions in PCDD/F emissions from the stack. It indicates that other emission
      sources of PCDD/Fs also have a notable impact on the area under direct influence
      of the MSWI.

PMID- 12046951
TI  - Removal of dyes from an artificial textile dye effluent by two agricultural waste
      residues, corncob and barley husk.
AB  - The use of a previously untried biosorbent, barley husk, for dye removal is
      compared to corncob. The effectiveness of adsorption as a means of dye removal
      has made it an ideal alternative to other more costly treatments. This paper
      deals with two low-cost, renewable biosorbents, which are agroindustrial by
      products, for textile dye removal. Experiments at total dye concentrations of 10,
      20, 30, 40, 50, 100, 150, and 200 mg l(-1) were carried out with an artificial
      effluent consisting of an equal mixture of five textile dyes. The effects of
      initial dye concentration, biosorbent particle size, dose of biosorbent,
      effective adsorbance, and dye removal kinetics were examined. One gram (per 100
      ml) of < or = 600 microm corncob was found to be effective in removing a high
      percentage of dyes at a rapid rate (92% in 48 h). One gram of I x 4 mm barley
      husk was found to be the most effective weight and particle size combination for
      the removal of dyes (92% in 48 h). The results illustrate how barley husk and
      corncob are effective biosorbents concerning the removal of textile dyes from
      effluent.

PMID- 12046953
TI  - Risk assessment at hazardous waste-contaminated sites with variability of
      population characteristics.
AB  - Risk assessment is considered to be an effective scientific tool which enables
      decisionmakers to manage hazardous waste-contaminated sites in a cost-effective
      manner while preserving public health. However, the current risk assessment
      framework proposed by the US Environmental Protection Agency (US EPA) has
      limitations in addressing the true variability of population characteristics.
      This study proposed a methodology that is different from the existing framework
      by accounting for the true variability of population characteristics. The key
      differences of the proposed methodology and the existing framework are the (1)
      use of the transient exposure concentration; (2) use of the entire population
      rather than a representative ideal individual; (3) use of age- and gender-based
      population subgroups to represent population characteristics; (4) use of a
      population growth model to represent growth dynamics; and (5) presentation of
      risk through a risk profile with risk summarized through a single indicator,
      potential cancer incidences (PCI). The proposed methodology was applied in a
      ground water contamination scenario due to benzene to determine its
      applicability. The results of the study showed that age-based variability of
      population characteristics is important in predicting the population risk while
      gender played a small role. The existing US EPA methodology and its variation
      using age-independent variability of population characteristics overestimate the
      risk given by PCI substantially, and therefore, the decisions can lead to costly
      cleanup goals. Population risk is not a single value but a distribution due to
      the contribution from ditferent individuals of the exposed population. Hence, the
      decision criterion proposed in this study, PCI, is found to be a useful indicator
      to describe population carcinogenic risk to the society under a variety of
      conditions and scenarios.

PMID- 12046952
TI  - Potential source of asbestos in non-asbestos textile manufacturing company.
AB  - Recently, a worker with lung carcinoma and a metastatic brain tumor was diagnosed
      as having a work-related disease. He had been employed in a non-asbestos textile
      company for 25 years. Consequently, to identify and explore possible causative
      agents for lung cancer in a non-asbestos textile manufacturing company and
      establish a causal relationship between exposure and lung cancer, an
      epidemiological investigative study was conducted and the work processes the
      worker was engaged in were examined. Air samples were taken from the workplace
      and during the drilling processes, and a suspected causative material was
      analyzed. The study revealed that the subject had been employed in the non
      asbestos textile manufacturing company for 25 years from 1973 and his
      responsibilities included repairing spinning machines. In particular, the subject
      was involved in drilling B-bushings that were used to protect against gear
      abrasion in the spinning machines. An analysis of the B-bushings using a
      transmission electron microscope equipped with an energy dispersive X-ray
      analyzer indicated that they contained crocidolite asbestos fibers. Air samples
      obtained when drilling the B-bushings clearly indicated that the subject had most
      likely been exposed to crocidolite fibers when installing the B-bushings in the
      spinning machines. The frequency and duration of the work suggested that there
      would be a sufficient degree of exposure to crocidolite fibers to cause lung
      cancer. Except for smoking and asbestos exposure, no other chemical exposure was
      suspected for developing lung cancer in the workplace. Smoking appeared to be
      more of a potentiating risk factor in conjunction with the asbestos exposure.
      Accordingly, this case may provide significant evidence in identifying the cause
      of the mesothelioma or lung carcinoma found among workers in non-asbestos textile
      manufacturing companies elsewhere.

PMID- 12046954
TI  - Characterization of water-soluble ion species in urban ambient particles.
AB  - Concentrations and distributions of water-soluble ion species contained in
      ambient particles were measured in a coastal urban area, Kaohsiung City, Taiwan.
      PM10 and PM2.5 samples were collected using a dichotomous sampler from November
      1998 to April 1999 and were analyzed for water-soluble ion species with ion
      chromatography. On the average, ion species measured in this study accounted for
      42.2% of the PM2.5 and 35.7% of the PM10. It was found that SO4(2-) , NO3-, and
      NH4+ dominated the identifiable components within both fine (PM2.5) and coarse
      (PM2.5-10) fractions, and occupied 90.0% and 80.6% of total dissolved ionic
      concentrations for PM2.5 and PM10. The secondary aerosol formed through the
      NOx/SO2 gas-to-particle conversion was estimated based on the oxidation ratio of
      sulfur and nitrogen (SOR and NOR, respectively), i.e., sulfate sulfur/nitrate
      nitrogen to total sulfur/total nitrogen. The average SOR/NOR values were
      0.25/0.07 and 0.29/0.12 for PM25 and PM10, respectively. The high SOR and NOR
      values obtained in this study suggested that there existed a secondary formation
      of SO4(2-) from SO2 along with NO3- from NOx in the atmosphere.

PMID- 12046955
TI  - Leaching of nickel and copper from soil contaminated by metallurgical dust.
AB  - The paper presents the results of the laboratory percolation experiment simulated
      soil contamination by emissions from a Ni-Cu smelter. Humus (Ao horizon) columns
      were transferred to lysimeters from an illuvial, humic, ferriferous forest podzol
      site. Fine metallurgical dust containing Ni and Cu was layered on the columns and
      irrigated with sulphuric acid solutions at pH 3, 4, 5, and 6. Irrigation for 19
      months indicated that the leaching of metals down the humus column was greatest
      at pH 6. Calculations indicated that it would take 160-270 years for complete
      leaching of Ni from the Ao layer, and 100-200 years for Cu, depending on the dust
      composition. Natural decontamination of affected soils will take centuries.

PMID- 12046956
TI  - Bioaccumulation of lead in Xenopus laevis tadpoles from water and sediment.
AB  - The overall objective of this research was to monitor the uptake kinetics of lead
      in an amphibian model and correlate metal content with embryo development. Based
      upon the concentration of lead found in the water and sediment of a Louisiana
      swamp adjacent to a Superfund site, a controlled laboratory experiment exploring
      lead uptake from water and sediment by Xenopus laevis tadpoles was conducted. For
      5 weeks, tadpoles were exposed to water and a simulated sediment, kaolin, spiked
      with 1, 5, or 10 times the concentration of lead found in field water and
      sediment samples. Additionally, organisms were exposed to the 5 x condition for 3
      and 6 weeks. The experimental controls consisted of unexposed tadpoles and ones
      exposed to lead originating from water or sediment exclusively. At the end of the
      exposure periods, developmental data, i.e., body weight and developmental stage,
      were recorded, and the tadpoles were analyzed for whole body lead concentration.
      Lead extraction was accomplished by dry ashing, and its amount was quantified
      polarographically. Results showed that lead inhibited the normal development of
      these amphibians, in a manner that generally was more severe as exposure level
      increased. The hindrance of tadpole development also coincided with an increase
      in whole body lead concentration at higher exposures. Temporally, at the 5 x
      exposure concentration, the mean lead level increased with time, but this
      difference was not statistically significant (P<.05). Additionally, control
      animals exposed to lead (either in water or in sediment) showed no statistical
      difference with regard to weight and lead uptake, indicating that lead
      originating from both water and sediment is incorporated into the tadpole. The
      controlled laboratory experimental protocol used here is thus capable of
      investigating the uptake of a single metal (Pb in this case) and determining its
      effect on the development of tadpoles while differentiating the significance of
      multiple sources of exposure.

PMID- 12046957
TI  - Determination of total petroleum hydrocarbons and heavy metals in soils within
      the vicinity of facilities handling refined petroleum products in Lagos
      metropolis.
AB  - This article discusses the determination of total petroleum hydrocarbons (TPH)
      and heavy-metal contamination in soils within areas of refined petroleum products
      handling in Lagos metropolis. Soil samples were collected randomly from two
      petrol stations, two auto-mechanic workshops, and a National Electric Power
      Authority (NEPA) station. Control samples were taken from two low-density
      residential areas. TPH were estimated gravimetrically following standard methods
      of TPH analysis, while the heavy metals were determined by atomic absorption
      spectrophotometry. Sites studied had higher levels of TPH and heavy metals
      compared to the control samples. For TPH, the petrol stations have mean values of
      399.83+/-106.19 and 450.83 +/- 90.58 microg/g, respectively; mechanic workshops,
      362.60 +/- 185.84 and 428.55 +/- 119.00 microg/g, respectively; while the NEPA
      station has 356.20 +/- 210.30 microg/g compared to the control mean of 26.63 +/-
      4.58. It revealed that the improper handling of refined petroleum products are
      potential sources of soil contamination in the sampled sites. This is indicated
      by the statistically significant levels of TPH and heavy metals observed between
      the control samples and those collected from the petroleum products handling
      sites. Bioremediation using microorganisms and plants is recommended.

PMID- 12046958
TI  - Transuranic biokinetic parameters for marine invertebrates--a review.
AB  - A catalogue of biokinetic parameters for the transuranic elements plutonium,
      americium, curium, neptunium, and californium in marine invertebrates is
      presented. The parameters considered are: the seawater-animal concentration
      factor (CF); the sediment-animal concentration ratio (CR); transuranic
      assimilation efficiency; transuranic tissue distribution and transuranic
      elimination rates. With respect to the seawater-animal CF, authors differ
      considerably on how they define this parameter and a seven-point reporting system
      is suggested. Transuranic uptake from sediment by animals is characterised by low
      CRs. The assimilation efficiencies of transuranic elements in marine
      invertebrates are high compared to vertebrates and mammals in general and the
      distribution of transuranics within the body tissue of an animal is dependent on
      the uptake path. The elimination of transuranics from most species examined
      conformed to a standard biphasic exponential model though some examples with
      three elimination phases were identified.

PMID- 12046959
TI  - Framework for the uncertainty assessment in the impact pathway analysis with an
      application on a local scale in Spain.
AB  - The estimation of damage estimates due to air emissions gives important basic
      knowledge for decision-making on the level of environmental politics and business
      strategies. Nowadays, a frequently applied method to estimate environmental
      damages is the Impact Pathway Analysis (IPA), which can be easily carried out
      using models such as EcoSense or PathWays. These models produce results in a
      relatively short term. However, there is a lack of reliability in the results. As
      in many other environmental software tools, the uncertainty is the key problem
      that makes it difficult to convince decision-makers by the outcomes of a study.
      Therefore, a framework that allows assessing the uncertainties within studies in
      which the IPA is applied on a local scale has been developed. In this assessment
      framework, the uncertainties of the used parameters, including their spatial and
      temporal variability, are taken into account. As the model is processing a huge
      quantity of data, one step of the assessment consists of a screening procedure to
      determine the parameters that are supposed to be fixed. For the other data,
      probability distributions have to be selected and classified into two groups:
      extensively available data for which average and standard deviation can be
      calculated and data based on little information. A quantification of the
      uncertainty can be completed by a stochastic model in the form of Monte Carlo
      (MC) simulation on the basis of the framework. As an illustration of the
      framework, we have applied it to a study on the installation of an advanced gas
      treatment in the municipal waste incinerator of Tarragona. It can be shown that
      the presented stochastic approach gives a lower geometric deviation than the
      analytical one and that the new gas treatment reduces the environmental damages
      without any doubt.

PMID- 12046960
TI  - Radon level in dwellings and its correlation with uranium and radium content in
      some areas of Himachal Pradesh, India.
AB  - LR- 115 plastic track detectors have been used to measure indoor radon level in
      some dwellings of Una district, Himachal Pradesh, India. The annual average radon
      concentration in dwellings in most of the villages falls in the range of the
      action level recommended by the International Commission on Radiological
      Protection. The radon values in some of the dwellings exceed the action level and
      may be unsafe from the health hazard point of view. The indoor radon values are
      in general higher in winter than in summer. Uranium, radium and radon exhalation
      studies have also been carried out in soil samples collected from these areas. A
      good correlation is obtained between uranium concentration in the soil and indoor
      radon in dwellings. The soil radon exhalation rate also correlates with the
      uranium concentration in soil.

PMID- 12046961
TI  - Species differences in normal brain cholinesterase activities of animals and
      birds.
AB  - The normal cholinesterase activity in brain tissue was measured in 15 mammalian
      and 44 avian species using the Ellman method. Enzyme activity exhibited
      considerable interspecies variability. In mammals, the enzyme activities ranged
      from approximately 2 to 10 micromole/min/g of wet tissue. With the exception of
      the carnivores (dog, fox, coyote), no consistency of the enzyme activity could be
      identified in related mammalian species. The range of interspecies differences
      associated with avian cholinesterase activity were approximately double when
      compared to the mammalian species tested. Enzyme activities in avian species
      ranged from approximately 10 to 30 micromole/min/g. Comparisons for uniformity of
      enzyme activity between closely related avian species were poor in most
      instances. The considerable variability of the brain cholinesterase activities in
      avian and mammalian species illustrates the need for reliable normal values for
      individual species to improve ability to monitor environmental exposure or to
      confirm acute poisonings associated with organophosphate or carbamate
      insecticides.

PMID- 12046962
TI  - Acute poisoning with psychoactive substances in the 1990-2000 period of
      socioeconomic transition and crisis in Plovdiv region, Bulgaria.
AB  - The "opening" of the post-totalitarian societies of Eastern Europe increased the
      illegal spread of psychoactive substances (PAS) in the past decade. We studied
      psychoactive substance acute poisoning (PAS AP)--types of toxic agents involved,
      incidence rates, and their changes--as indirect indicators of the
      characteristics, magnitude and development of the problem in Bulgaria during the
      1990-2000 period of socioeconomic transition and crisis after collapse of
      communism. The study analyzed retrospectively the caseload of all 571 PAS acute
      poisonings that occurred in the territory: 417 men (73%) and 154 women (27%);
      mean age 24.07y (range 10-75). The number of all AP and PAS AP showed a marked
      increase during the last 3years of the studied period, especially in 2000. The
      average PAS AP incidence rate for 1998-2000 (13.50/100,000) compared to the mean
      value for the preceding period 1990-1997 (5.76/100,000) showed a 2.34 fold
      increase. Acute alcohol intoxication was 62.7%, of all PASAP; the opioid 15.2%
      (heroin 11.0%, other opioids 4.2%); prescribed and over the counter drugs 12.6%;
      inhalants 1.1%; cannabis 1.1%; and cocaine 0.7%. Amphetamine (or amphetamine
      like), hallucinogens and phencyclidine (or phencyclidine-like) AP were not
      encountered. The average percentage of alcohol AP for 1998-2000 compared to the
      preceding 1990-1997 dropped from 78.12% to 44.72% (1.75 fold), while that of
      opioids rose from 6.59% to 26.47% (4.02 fold), and that of the other drugs group
      from 12.22% to 21.78% (1.78 fold increase). The new non-alcoholic PAS AP (heroin,
      cocaine, inhalants and cannabis AP, as indirect indicators of narcotic exposure)
      showed a rapid increase. The data showed they are expanding and catching up with
      alcohol as a new cause of substance-related problems, thus becoming one of the
      important health and social problems of post-totalitarian society.

PMID- 12046963
TI  - Effect of lonophore supplementation on selected serum constituents of sheep
      consuming locoweed.
AB  - The effects of ionophore supplementation on selected serum constituents of sheep
      consuming locoweed were investigated. Sixteen sheep were allotted by weight to a
      2x2 factorial arrangement of treatments: 1) no locoweed, no lasalocid, 2) no
      locoweed, 0.75 mg lasalocid/kg BW, 3) 0.5 mg swainsonine/kg BW, no lasalocid, 4)
      0.5 mg swainsonine/kg BW, 0.75 mg lasalocid/kg BW. Swainsonine was provided by
      locoweed (Oxytropissericea), and sheep were fed a blue grama based diet at 2.5%
      BW for a 35 d treatment period. Diets were formulated to be isocaloric and
      isonitrogenous. Blood samples were collected on d 1, 7,14, 21, 31 and 35 to
      determine serum swainsonine concentration, alkaline phosphatase, total iron,
      aspartate aminotransferase, g-glutamyltransferase, and lactate dehydrogenase
      activity and total cholesterol, and triglyceride concentrations. No lasalocid by
      locoweed interaction (P > 0.4) was noted for any response variable measured.
      Average daily gains (P = 0.4) and orts (P = 0.7) were not affected by the
      treatments. No lasalocid treatment (P = 0.7) or day (P = 0.1) effect of serum
      swainsonine was observed. A locoweed by day interaction (P < 0.0001) of serum
      alkaline phosphatase was detected. Alkaline phosphatase levels were elevated (P <
      0.01) for locoweed treated sheep at 24 h following initial exposure and remained
      elevated throughout the trail. Total iron was suppressed (P < 0.08) in locoweed
      fed sheep. A day effect (P < 0.02) was observed for serum iron. However, no
      linear, quadratic, or cubic effects of day were noted (P >0.2). A locoweed by day
      interaction (P < 0.0001) of serum aspartate aminotransferase and g
      glutamyltransferase was detected. Aspartate aminotransferase levels were elevated
      (P < 0.0001) by d 7 for locoweed treated animals and remained elevated throughout
      the trial. g--Glutamyltransferase levels were suppressed (P < 0.0001) by day 7
      for locoweed treated animals and remained suppressed throughout the trial. A
      locoweed by day interaction (P = 0.06) of serum cholesterol was detected.
      However, no linear, quadratic, or cubic effects of day were detected (P = 0.2).
      Lasalocid treatment had no effect on any serum constituent measured. Use of
      lasalocid in grazing animals should not increase the likelihood of locoweed
      intoxication.

PMID- 12046964
TI  - Hypoglycemic and hypotriglyceridemic effects of tolbutamide in triphenyltin
      chloride-induced diabetic rabbits.
AB  - Triphenyltin (TPT) induces transient hyperglycemia and hypertriglyceridemia in
      rabbits and hamsters through inhibition of the insulin release stimulated by
      glucose. The disturbed site in TPT-diabetes is a result of signal transduction
      occurring before the voltage-dependent Ca2+ channel. The ATP-sensitive K channel
      (KATP channel) is located immediately at the upstream signal of voltage dependent
      Ca2+ channels on the signaling pathway of insulin secretion. KATP channel
      produces depolarization by a signal of ATP through glucose metabolism and by
      stimulation from sulfonylurea drugs (tolbutamide, glibenclamide). To clarify if
      the insulin secretion that a KATP channel mediates is inhibited in vivo, we
      studied the effects of tolbutamide (a sulfonylurea) on changes in plasma glucose,
      triglyceride and insulin in TPT-diabetic rabbits prepared by po administration of
      100 mg TPT-chloride/kg bw. In TPT-diabetic rabbits, plasma glucose decreased to a
      minimum at about 50% and plasma triglyceride levels also decreased. Insulin
      release was detected after injecting = 10 mg tolbutamide/kg, and insulin was
      secreted much higher than in normal rabbits. These findings suggest that the
      insulin released by tolbutamide stimulus decreased the plasma glucose and
      triglyceride levels in the TPT-diabetic rabbits. Moreover, a possible mechanism
      to be considered is as follows: tolbutamide combines with sulfonylurea receptor;
      membrane depolarization is induced by a KATP channel with the signal of a
      sulfonylurea receptor; insulin is released. The inhibition of insulin secretion
      by TPT may be caused by a glucose metabolic disorder in beta cells before the
      occurrence of membrane depolarization due to closed KATP channels interacting
      directly with a sulfonylurea receptor.

PMID- 12046965
TI  - Intoxication of cattle by the fruits of Melia azedarach.
AB  - Melia azedarach fruits were administered at single doses ranging from 5 to 30
      g/kg bw to 10 calves. The animals dosed with 25 g/kg bw and 30 g/ kg bw died, as
      well as 1/2 cattle that received 15 g/kg bw. Clinical signs were depression,
      ruminal stasis, anorexia, diarrhea, incoordination, muscle tremors, difficulty to
      stand, sternal recumbence, hypothermia and dyspnea. Serum AST and CPK were
      increased. Signs appeared 4 to 24 h after dosing and the clinical manifestations
      continued for 20 to 72 h. Macroscopic findings included congestion of the
      intestine, focal or diffuseyellow discoloration of the liver, and brain
      congestion. LiQuid content was in rumen, reticulum and intestines. The liver had
      swollen and vacuolated hepatocytes, and necrotic hepatocytes were scattered
      throughout the parenchyma or concentrated in the periacinar zone. Degenerative
      and necrotic changes were in the epithelium of the forestomachs. There was also
      necrosis of lymphoid tissue. Skeletal muscles had hyaline degeneration and fiber
      necrosis.

PMID- 12046966
TI  - Endocrine and respiratory responses to ergotamine in Brahman and Hereford steers.
AB  - Ergot alkaloids are considered causative agents of fescue toxicosis, a syndrome
      experienced by cattle consuming tall fescue (Festuca arundinacea) infected with
      the fungal endophyte Neotyphodium coenophialum. One sign of fescue toxicosis in
      cattle is severe hyperthermia. This study assessed hormonal responses to
      ergotamine in heat-sensitive and heat-tolerant cattle. Seven Hereford (heat
      sensitive, Bos taurus) and 7 Brahman (heat-tolerant, Bos indicus) steers on a
      fescue-free diet received ergotamine tartrate iv. Blood was sampled every 15 min
      for 2 h before and 4 h after dosing for determination of circulating hormonal
      changes. Respiration rates were recorded hourly. Ambient temperature and relative
      humidity averaged 31C and 48%, respectively, during sampling. A breed x time
      interaction existed (p < 0.01) for plasma prolactin, LH, insulin, glucagon,
      cortisol, triiodothyronine and glucose concentrations. The breed x time
      interaction tended to affect (p = 0.14) growth hormone and influenced (p < 0.01)
      respiration rates. Ergotamine reduced (p < 0.01) plasma LH and increased (p <
      0.01) growth hormone concentrations in Brahman. Both breeds responded to
      ergotamine with increased (p < 0.01) plasma cortisol, glucagon, and glucose and
      reduced (p < 0.01) insulin concentrations. The magnitude of response for
      cortisol, insulin, and glucose were greater for the Brahman. Ergotamine increased
      (p < 0.01) plasma triiodothyronine and respiration rates in Hereford, whereas
      these traits were unaltered in Brahman. Acute ergotamine exposure generally
      resulted in similar effects on Brahman and Hereford steers. The triiodothyronine
      and respiratory comparisons revealed modified responses in Brahman that suggest a
      potential benefit of using heat-tolerant genetics to reduce the adverse effects
      of fescue toxicosis in cattle.

PMID- 12046967
TI  - Ricinus communis cake poisoning in a dog.
AB  - A fatal case of canine poisoning by castor bean (Ricinus communis L) cake used as
      fertilizer is described, heat treatment The process of R communis cake production
      should include heat treatment to reduce the risk if the product is accidentally
      ingested by pets or humans.

PMID- 12046968
TI  - Erythropoietin overdose treated with emergent erythropheresis.
AB  - Erythropoietin (EPO) is commonly used to treat anemias secondary to renal
      failure, malignancy, and AIDS. Although therapeutic complications are well
      described, overdose is rare. A 42-y-o man with AIDS confused his instructions for
      self-administration of interferon and EPO and began injecting himself daily with
      10,000 units of EPO for several weeks. He presented with confusion, pain in his
      abdomen and feet, and a hemoglobin of 23.2 g/dLwith a hematocrit of 77.1%. The
      patient was treated with iv fluids, phlebotomy and 2 sessions of erythropheresis
      which removed 898 mL and 640 mL of red blood cells, respectively; his hemoglobin
      remained between 12-14 g/dL and symptoms resolved. His only sequelae involved
      skin loss over his toes, which did not require grafting. This rare case of EPO
      overdose highlights the complications of essential erythrocytosis, with central
      nervous system, peripheral, and presumed mesenteric ischemia.

PMID- 12046969
TI  - Cattle intoxication from Enterolobium contortisiliquum pods.
AB  - Three outbreaks of hepatogenous photosensitization caused by pods of Enterolobium
      contortisiliquum are reported in cattle. Clinical signs were anorexia,
      depression, photosensitization and abortion. Most affected cattle recovered in 30
      40 d. At necropsies, liver was present, the gallbladder was enlarged and
      edematous, and numerous seeds of E contortisiliquum were in the forestomachs and
      abomasum. Fruits of the plants administrated to 2 calves produced clinical signs
      and 2/4 died. Clinical chemistry, gross necropsies and histopathology confirmed
      gastrointestinal irritation and liver degeneration. One calf dosed with only E
      contortisiliquum leaves did not develop clinical signs.

PMID- 12046970
TI  - Acute quetiapine overdose in an eleven-year-old girl.
AB  - We present a case of acute Quetiapine (SeroQuel) overdose in an 11-y-old girl who
      ingested 1,300 mg (22.2 mg/kg bw). Initial lethargy developed within I h followed
      by an episode of agitation and combativeness 3 h after ingestion. After treatment
      with lorazepam the patient experienced extended somnolence followed by return to
      normal mental status 16 h after ingestion. No cardiotoxic or laboratory
      abnormalities were found. This is the first report of acute Quetiapine overdose
      in an adolescent and suggests a relatively benign clinical course.

PMID- 12046971
TI  - Acute pancreatitis and acute renal failure complicating doxylamine succinate
      intoxication.
AB  - Doxylamine succinate is an antihistaminic drugwith additional hypnotic,
      anticholinergic and local anesthetic effects first described in 1948. In Korea
      and many other countries, it is a common-over-the counter medication frequently
      involved in overdoses. Clinical symtomatology of doxylamine succinate overdose
      includes somnolence, coma, seizures, mydriasis, tachycardia, psychosis, and
      rhabdomyolysis. A serious complication may be rhabdomyolysis with subsequent
      impairment of renal function and acute renal failure. We report a case of acute
      renal failure and acute pancreatitis complicating a doxylamine succinate
      intoxication.

PMID- 12046972
TI  - Survival after ethylene glycol poisoning in a patient with an arterial pH of
      6.58.
AB  - This ethylene glycol poisoning case had a blood pH of 6.58 and severe hypothermia
      (30.9 C). The patient received supportive care with dialysis and ethanol therapy.
      He survived in his premorbid state after 23 days in the hospital. A similar case
      survived ethylene glycol poisoning neurologicaly intact with an initial pH of
      6.46. Although severe acidosis in the presence of serious illness is usually
      associated with a poor prognosis, our case emphasized the importance of
      aggressive supportive care and antidotal therapy for ethylene glycol poisoning
      even when there is a low pH.

PMID- 12046973
TI  - A possible trend suggesting increased abuse from Coricidin exposures reported to
      the Texas Poison Network: comparing 1998 to 1999.
AB  - Coricidin products seemed to be one of the over-the-counter medications being
      reportedly abused by adolescents, as observed from the Texas Poison Center
      Network data. This retrospective chart review investigated the occurrence of
      abuse, developed a patient profile, and defined the clinical effects resulting
      from the abuse of Coricidin products. Data collected from the Texas Poison Center
      Network Toxic Exposure Surveillance System database included human exposures
      between 1998 and 1999, patients > or = 10y old, intentional use or abuse, and
      single substance ingestion of I of the tablet formulations of Coricidin. Thirty
      three cases from 1998 and 59 cases from 1999 were reviewed. Of these cases, 85%
      met the inclusion criteria. Of the 7 medications searched, only 4 substances were
      coded for: Coricidin D, Coricidin D (long acting), Coricidin D (cold, flu &
      sinus) and Coriciding HBP. These contain a combination of dextromethorphan
      hydrobromide, chlorpheniramine maleate, phenylpropanolamine hydrochloride, and
      acetaminophen. Of the 78 cases, 63% were male and 38% were female. The mean age
      was 14.67 years, 77% being between 13 to 17 years old. Eighteen different
      symptoms were reported: tachycardia 50%, somnolence 24.4%, mydriasis and
      hypertension 16.7%, agitation 12.8%, disorientation 10.3%, slurred speech 9%,
      ataxia 6.4%, vomiting 5.1%, dry mouth and hallucinations 3.9%, tremor 2.6%, and
      headache, dizziness, syncope, seizure, chest pain, and nystagmus each 1.3%; 12.8%
      of the calls originated from the school nurse. The incidence of abuse reported
      increased 60% from 1998 to 1999. This worrisome trend suggests increased abuse of
      these products.

PMID- 12046974
TI  - Utility of acetaminophen screening in unsuspected suicidal ingestions.
AB  - Acetaminophen (APAP) is a common overdosed medication. Because of the lack of
      specific symptoms associated with initial toxicity, potential unsuspected APAP
      toxicity is a concern in suicidal ingestions. To identify the likelihood of
      unsuspected APAP toxicity in suicidal ingestions, we performed a retrospective
      study of all suicidal ingestions without a history of APAP exposure reported to a
      poison control center over a 6-mo period. History, symptoms, and APAP levels to
      assessed the incidence of unsuspected APAP ingestions. In a total of 471 cases,
      151 had APAP levels requested but not documented in our records. Of the remaining
      320 cases, 23 (7.2%) had APAP levels > 10 microg/mL. Twelve patients were treated
      with Nacetylcysteine, 7 patients (2.2 %) had potentially toxic levels, and 5
      patients had non-toxic or uninterpretable levels. Although the overall risk of
      unsuspected acetaminophen toxicity in suicidal ingestions is small, the definite
      risk in this treatable entity warrants universal APAP screening in all suicidal
      ingestions.

PMID- 12046975
TI  - The safety of intravenously administered vitamin K.
AB  - Literature sources suggest that iv vitamin K is associated with significant
      adverse side effects. Systematic study and documentation is lacking. In this 2-y
      retrospective review, 100 sequential doses of iv administered vitamin K in 45
      patients were identified by computer-generated pharmacy utilization reports in an
      adult teaching hospital. Charts were reviewed for complications following
      infusion of vitamin K, including specific abnormalities during the 90-min period
      post-administration: systolic blood pressure <90, heart rate <60 or >120, rash,
      shortness of breath, and syncope. Complete post-administration data were
      available for 60/100 doses. One episode of clinically insignificant transient
      hypotension was identified. Progress notes, discharge summaries and a concurrent
      survey of adverse drug reaction reports identified no complications related to
      the use of iv vitamin K. In this series, the iv administration of vitamin K did
      not pose a clinically significant risk.

PMID- 12046976
TI  - Identification of swainsonine as a glycoside inhibitor responsible for Sida
      carpinifolia poisoning.
AB  - The indolizidine alkaloid swainsonine has been identified as the toxic
      constituent of Sida carpinifolia, a native perennial shrub-like plant, reported
      to produce neurological disorders in goats and ponies in southern Brazil.
      Swainsonine was detected in dry ground plant material after extraction and
      analysis by both liquid and gas chromatography mass spectrometry. The swainsonine
      concentration was 0.006% on a dry weight basis. The clinical and pathological
      features of this lysosomal storage disease were similar to those observed in
      Swainsona, Oxytropis, Astragalus, and Ipomoea poisonings with multiple cytoplasm
      vacuoles in neurons, acinar pancreatic cells, hepatocytes, and renal tubular
      cells.

PMID- 12046977
TI  - Wasting and death in cattle associated with chronic grazing of Brachiaria
      decumbens.
AB  - Progressive wasting was observed in 4/1000 steers grazing Brachiaria decumbens
      pastures. Yellow liver and whitish hard nodules in the mesenteric and hepatic
      lymph nodes were observed at necropsy. At histologic examination multifocal
      accumulation of foamy macrophages were in the livers, spleens, lmph nodes, and
      intestinal submucosa. It is suggested that the wasting syndrome was due to the
      intestinal granulomatous lesions of B decumbens.

PMID- 12046978
TI  - Reliability of maternal reporting in identifying major congenital malformations.
AB  - We compared maternal reports of major congenital malformations with physicians'
      reports in a teratology counseling service. The reports of women followed during
      gestation were matched to those submitted by physicians caring for the infants.
      In 153/165 cases neither the mother nor the physician described major
      malformations. There were 12 cases where both mother and physician described
      similar major malformations. In several of them the mother used non-medical terms
      (eg "hole in the heart"). Maternal reports of major anomalies were in close
      agreement with physicians' reports. This lends credibility to research based on
      pregnancy follow-up with maternal reports that are corroborated by physicians'
      reports.

PMID- 12046979
TI  - The charcoal debate: its grit and grime.

PMID- 12046980
TI  - Molecular diversity of structure and function of the voltage-gated Na+ channels.
AB  - A variety of different isoforms of voltage-sensitive Na+ channels have now been
      identified. The recent three-dimensional analysis of Na+ channels has unveiled a
      unique and unexpected structure of the Na+ channel protein. Na+ channels can be
      classified into two categories on the basis of their amino acid sequence, Nav1
      isoforms currently comprising nine highly homologous clones and Nax that
      possesses structure diverging from Nav1, especially in several critical
      functional motifs. Although the functional role of Nav1 isoforms is primarily to
      form an action potential upstroke in excitable cells, recent biophysical studies
      indicate that some of the Nav1 isoforms can also influence subthreshold
      electrical activity through persistent or resurgent Na+ currents. Nav1.8 and
      Nav1.9 contain an amino acid sequence common to tetrodotoxin resistant Na+
      channels and are localized in peripheral nociceptors. Recent patch-clamp
      experiments on dorsal root ganglion neurons from Nav1.8-knock-out mice unveiled
      an additional tetrodotoxin-resistant Na+ current. The demonstration of its
      dependence on Nav1.9 provides evidence for a specialized role of Nav1.9, together
      with Nav1.8, in pain sensation. Although Nax has not been successfully expressed
      in an exogenous system, recent investigations using relevant native tissues
      combined with gene-targeting have disclosed their unique "concentration"
      sensitive but not voltage-sensitive roles. In this context, these emerging views
      of novel functions mediated by different types of Na+ channels are reviewed, to
      give a perspective for future research on the expanding family of Na+ channel
      clones.

PMID- 12046981
TI  - Pharmacological, pharmacokinetic and clinical properties of olopatadine
      hydrochloride, a new antiallergic drug.
AB  - Olopatadine hydrochloride (olopatadine, 11-[(Z)-3-(dimethylamino)propylidene]
      6,11-dihydrodibenz[b,e]oxepin-2-acetic acid monohydrochloride) is a novel
      antiallergic/histamine H1-receptor antagonistic drug that was synthesized and
      evaluated in our laboratories. Oral administration of olopatadine at doses of
      0.03 mg/kg or higher inhibited the symptoms of experimental allergic skin
      responses, rhinoconjunctivitis and bronchial asthma in sensitized guinea pigs and
      rats. Olopatadine is a selective histamine H1-receptor antagonist possessing
      inhibitory effects on the release of inflammatory lipid mediators such as
      leukotriene and thromboxane from human polymorphonuclear leukocytes and
      eosinophils. Olopatadine also inhibited the tachykininergic contraction in the
      guinea pig bronchi by prejunctional inhibition of peripheral sensory nerves.
      Olopatadine exerted no significant effects on action potential duration in
      isolated guinea pig ventricular myocytes, myocardium and human ether-a-go-go
      related gene channel. Olopatadine was highly and rapidly absorbed in healthy
      human volunteers. The urinary excretion of olopatadine accounted for not less
      than 58% and the contribution of metabolism was considerably low in the clearance
      of olopatadine in humans. Olopatadine is one of the few renal clearance drugs in
      antiallergic drugs. Olopatadine was shown to be useful for the treatment of
      allergic rhinitis and chronic urticaria in double-blind clinical trials.
      Olopatadine was approved in Japan for the treatment of allergic rhinitis, chronic
      urticaria, eczema dermatitis, prurigo, pruritus cutaneous, psoriasis vulgaris and
      erythema exsudativum multiforme in December, 2000. Ophthalmic solution of
      olopatadine was also approved in the United States for the treatment of seasonal
      allergic conjunctivitis in December, 1996 (Appendix: also in the European Union,
      it was approved in February 2002).

PMID- 12046982
TI  - Involvement of glutamate receptors within the central nucleus of the amygdala in
      naloxone-precipitated morphine withdrawal-induced conditioned place aversion in
      rats.
AB  - Chronic use of morphine leads to physical and psychological dependence. The
      amygdala is known to be involved in the expression of emotion such as anxiety and
      fear, and several studies have shown that the central nucleus of the amygdala
      (CeA) is involved in morphine dependence. In the present study, we investigated
      the role of glutamate receptors within the CeA in the negative affective
      component of morphine abstinence by evaluating naloxone-precipitated withdrawal
      induced conditioned place aversion (CPA) in morphine-dependent rats. We found
      that microinjection of the AMPA/kainate-glutamate-receptor antagonist CNQX (30
      nmol/side) into the bilateral CeA significantly attenuated the naloxone
      precipitated withdrawal-induced CPA, as well as several somatic signs, in
      morphine-dependent rats, without preference or aversive effects by itself in non
      dependent rats. Furthermore, microinjection of the non-competitive NMDA-receptor
      antagonist MK-801 (30 nmol/side) or competitive NMDA-receptor antagonist D-CPPene
      (0.01 and 0.1 nmol/side) into the CeA significantly attenuated the naloxone
      precipitated morphine withdrawal-induced CPA, but not somatic withdrawal signs.
      These results suggest that the activation of AMPA /kainate and NMDA receptors
      within the CeA play a crucial role in the negative affective component of
      morphine abstinence.

PMID- 12046983
TI  - Involvement of adenosine A2 receptors in the changes of tissue factor-dependent
      coagulant activity induced by polymorphonuclear leukocytes in endothelial cells.
AB  - We have already reported that polymorphonuclear leukocytes (PMNs) could increase
      tissue factor-dependent coagulant activity (TF activity) in endothelial cells
      mediated by adhesion of PMNs to endothelial cells. In the present study, the role
      of adenosine receptors in the changes of TF activity and of adhesion between PMNs
      and endothelial cells was examined. The increases of the TF activity and adhesion
      were significantly reduced in a concentration-dependent manner by pretreatment of
      adenosine (0.1 and 1.0 mM); an adenosine A1/A2-receptor agonist, CGS-21680 (5, 10
      and 50 microM); and an adenosine A2-receptor agonist, 5'-(N-cyclopropyl)
      carboxamidoadenosine (CPCA; 1.0, 10 and 100 nM). An adenosine A2-receptor
      antagonist, 3,7-dimethyl-1-(2-propynyl) xanthine (DMPX; 1.0 and 100 nM),
      antagonized significantly the reduction of the TF activity and the adhesion
      induced by adenosine (1.0 mM), while 8-cyclopentyl-1,3-dimethylxanthine (CPDMX;
      1.0 and 100 nM), an adenosine A1-receptor antagonist, did not affect it. On the
      other hand, the TF activity and the adhesion were not changed by N6
      cyclohexyladenosine (CHA; 10 and 100 nM) and 2-chloro-N-cyclopentyladenosine
      (CCPA; 10 and 100 nM), adenosine A1-receptor agonists in the same conditions.
      These results suggest that the reduction in the TF activity stimulated by PMNs is
      closely related to the adhesive inhibition between PMNs and endothelial cells
      through the adenosine A2-receptor-mediated system.

PMID- 12046984
TI  - Effects of a typical I(Kr) channel blocker sematilide on the relationship between
      ventricular repolarization, refractoriness and onset of torsades de pointes.
AB  - The effects of a typical I(Kr) channel blocker sematilide on the relationship
      between ventricular repolarization, refractoriness and onset of torsades de
      pointes (TdP) were studied using the canine isolated, blood-perfused ventricular
      septum preparation with monophasic action potential (MAP) recording.
      Intracoronary infusion of sematilide (10-100 microg/min) prolonged the
      repolarization phase and effective refractory period, the extent of which was
      greater in the former than in the latter, resulting in prolongation of terminal
      repolarization process. Prolonging the basic pacing cycle length from 400 to 600
      ms and/or increasing the drug doses enhanced each of these actions. Reverse use
      dependence was obvious in the drug-induced prolongation of MAP duration, but it
      was less clear in the effective refractory period. More importantly, during
      sematilide infusion, in preparations paced at longer basic cycle length of 600 -
      2000 ms, TdP-like polymorphic ventricular tachycardia was repeatedly induced by
      an extra-stimulus applied on the terminal repolarization phase, which indicates
      the appearance of electrically vulnerable period. Prolonging the basic pacing
      cycle length and/or increasing the drug doses prolonged this electrically
      vulnerable period in parallel with the terminal repolarization phase. These
      results suggest that prolongation of the terminal repolarization process by
      sematilide would enhance the chance of conduction slowing at less complete
      repolarization levels, which may be associated with a high incidence of TdP
      induction.

PMID- 12046985
TI  - Prostate apoptosis response-4 involved in the protective effect of salvianolic
      acid B against amyloid beta peptide-induced damage in PC12 cells.
AB  - To observe the effect of salvianolic acid-B (SalB) against the cytoxicity of
      amyloid beta peptide (A-beta)(25-35) to PC12 cells, the cells were incubated with
      A-beta, and the cytoxicity was investigated by MTT, flow cytometry and a cell
      free apoptotic system. The expression of prostate apoptotic response-4 (Par-4)
      was detected by Western blot. Aged A-beta 10 micromol/L significantly inhibited
      the MTT reduction of PC12 cells, SalB1 micromol/L inhibited the toxicity induced
      by A-beta. In flow cytometric analysis, PC12 cells treated with A-beta exhibited
      degraded DNA content characteristic of apoptosis cells (1.53% vs 19.9%). PC12
      cells pretreated with SalB (10 nmol/L, 100 nmol/L, 1 micromol/L) manifested
      relatively low proportion of apoptosis (15.7%, 13.5%, 11.8%, respectively). SalB
      (10 nmol/L - 1 micromol/L) when added at the beginning of the cell free apoptotic
      reaction had no apparent effect on the nuclei apoptosis. Pretreatment of PC12
      cells with SalB largely prevented the increase in Par-4 expression of the cells
      when they were exposed to A-beta. The results suggest that Par-4 is involved in
      the protective effect of SalB against A-beta-induced damage in PC12 cells.

PMID- 12046987
TI  - Effects of angiotensin II on the renal interstitial concentrations of NO2/NO3 and
      cyclic GMP in anesthetized rats.
AB  - The present study was conducted to determine whether exogenous angiotensin II
      (Ang II) may increase the renal interstitial fluid concentrations of NO2/NO3
      (NOx) and cyclic guanosine monophosphate (cGMP) concomitantly and which Ang II
      receptor subtypes may induce these changes in anesthetized rats, using a
      microdialysis method. Ang II (50 ng/kg per min, i.v.) significantly increased
      mean blood pressure (MBP), extraction rates of renal interstitial NOx from 23.9+/
      1.0 to 31.2+/-1.9 pmol/min, and cGMP from 4.1+/-0.3 to 6.4+/-0.5 fmol/min, and
      decreased renal blood flow (RBF). The AT1-receptor antagonist CV11974 alone
      significantly increased RBF, but did not alter MBP, renal interstitial
      concentrations of NOx and cGMP. A superimposition of Ang II on CV11974 did not
      affect MBP and RBF, but significantly increased renal interstitial concentrations
      of NOx and cGMP. The AT2-receptor antagonist PD123319 alone did not change any of
      the parameters. However, superimposition of Ang II on PD123319 increased MBP and
      decreased RBF without any effects on renal interstitial concentrations of NOx and
      cGMP. These results suggest that Ang II stimulates NO production via the AT2
      receptor in the kidney.

PMID- 12046988
TI  - Dipeptidyl peptidase IV inhibition improves impaired glucose tolerance in high
      fat diet-fed rats: study using a Fischer 344 rat substrain deficient in its
      enzyme activity.
AB  - This study was performed to determine the effects of a high-fat diet on glucose
      metabolism after an oral glucose challenge in high-fat diet-fed dipeptidyl
      peptidase IV (DPP-IV) positive (+) and deficient (-) Fischer 344 (F344) rats and
      the effects of novel DPP-IV inhibitor NVP-DPP728 (1-[2-[(5-cyanopyridin-2
      yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine monohydrochloride salt) on
      glucose tolerance in high-fat diet-fed F344 rats. In DPP-IV(+) rats, a high-fat
      diet load caused impaired glucose tolerance, such as increases of plasma insulin
      and blood glucose concentrations after oral glucose challenge, compared with a
      standard chow-fed group. In contrast, no marked change in glucose tolerance was
      induced by the high-fat diet in DPP-IV(-) rats. Blood glucose concentrations in
      DPP-IV(-) rats after glucose challenge were significantly lower than in DPP-IV(+)
      rats under high-fat diet load conditions. In standard chow and high-fat diet-fed
      DPP-IV(+) rats, NVP-DPP728 significantly suppressed glucose excursions after
      glucose challenge by inhibiting the plasma DPP-IV activity, associated with the
      stimulation of early insulin secretion. NVP-DPP728 did not affect glucose
      tolerance in DPP-IV(-) rats under both conditions. These results indicate that
      the amelioration of glucose tolerance by NVP-DPP728 in DPP-IV(+) rats was
      directly due to the inhibition of plasma DPP-IV activity, which might be via the
      subsequent increase in endogenous incretin action.

PMID- 12046986
TI  - Characteristics of ATP-induced current through P2X7 receptor in NG108-15 cells:
      unique antagonist sensitivity and lack of pore formation.
AB  - ATP activates the mouse P2X7 receptor and induces a nonselective-cation current
      in NG108-15 cells. We investigated the effects of five receptor antagonists on
      the ATP-induced nonselective-cation current through P2X7 receptor (I(NS.P2X7)) in
      NG108-15 cells. Nonselective P2 receptor antagonists, RB-2, PPADS and suramin
      inhibited the I(NS.P2X7) with IC50 values of 4.3, 53 and 40 microM, respectively.
      However, KN-04, which is a potent antagonist of human P2X7 receptors but is not
      that of rat P2X7 receptors, had only a weak blocking effect. Furthermore,
      oxidized-ATP (300 microM), an antagonist of the P2X7 receptor-mediated pore
      formation, did not affect the I(NS.P2X7). Prolonged ATP application did not
      increase the membrane permeability to large molecules, N-methyl-D-glucamine or Yo
      Pro-1, indicating that pore-formation was not promoted by the P2X7 receptor
      activation in NG108-15 cells. These results suggest that antagonist sensitivities
      and pore-forming properties of the P2X7 receptors in NG108-15 cells are different
      from those of other cells types.

PMID- 12046989
TI  - Dipeptidyl peptidase IV inhibitor NVP-DPP728 ameliorates early insulin response
      and glucose tolerance in aged rats but not in aged Fischer 344 rats lacking its
      enzyme activity.
AB  - The aim of this study was to investigate the effects of aging on glucose
      metabolism after oral glucose challenge in aged dipeptidyl peptidase IV (DPP-IV)
      positive (+) Fischer 344 (F344), DPP-IV deficient (-) F344 and DPP-IV(+) Wistar
      rats and to determine the effect of a DPP-IV inhibitor NVP-DPP728 (1-[2-[(5
      cyanopyridin-2-yl)amino]ethylamino]acetyl-2-cyano-(S)-pyrrolidine
      monohydrochloride salt) on glucose tolerance in aged rats. Aging caused a
      decrease in early insulin response after an oral glucose challenge in aged Wistar
      or DPP-IV(+) F344 rats, but not in aged DPP-IV(-) F344 rats, compared with young
      control groups. Glucose tolerance after an oral glucose challenge in aged DPP-IV(
      ) F344 rats was better than in aged DPP-IV(+) F344 and Wistar rats associated
      with the preservation of the early insulin response. NVP-DPP728 improved the
      glucose tolerance after an oral glucose challenge by potentiating the early
      insulin response throughout the inhibition of plasma DPP-IV activity in aged DPP
      IV(+) Wistar and F344 rats. In contrast, NVP-DPP728 did not affect the glucose
      tolerance after an oral glucose challenge in aged DPP-IV(-) F344 rats. These
      results indicate that treatment with NVP-DPP728 ameliorated glucose tolerance in
      aged rats by the direct inhibition of plasma DPP-IV activity and presumably the
      subsequent increase in endogenous incretin action.

PMID- 12046990
TI  - Hyperpolarization-activated current I(h) in nucleus of solitary tract neurons:
      regional difference in serotonergic modulation.
AB  - The nucleus of solitary tract (NTS) contains diverse neural circuits responsible
      for basic vital functions. We examined the effect of serotonin (5-HT) on
      hyperpolarization-activated current (I(h)) in neurons acutely isolated from
      caudal, medial and rostral parts of the NTS. Caudal and medial NTS neurons showed
      a large amplitude of I(h) compared with rostral neurons. In these neurons,
      perfusion with 5-HT potentiated Ih amplitude in a concentration-dependent manner.
      The effect of 5-HT was blocked by NAN-190, a 5-HT1A receptor antagonist. Thus, 5
      HT1A receptors may regulate I(h) channel activity in caudal and medial NTS
      neurons.

PMID- 12046991
TI  - Inhibitory effect of olopatadine on antigen-induced eosinophil infiltration and
      the LFA-1 and Mac-1 expression in eosinophils.
AB  - The inhibitory effect of olopatadine, a new antiallergic drug, on antigen-induced
      eosinophil infiltration and its mechanisms were examined using the local
      sensitized rat allergic rhinitis model and isolated IL-5-stimulated rat
      peritoneal eosinophils. Olopatadine dose-dependently inhibited antigen-induced
      eosinophil infiltration in the nasal mucosa. Olopatadine dose-dependently
      repressed the IL-5-induced expressions of CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac
      1) on rat peritoneal eosinophils. However, olopatadine had no effect on IL-5
      induced CD49d/CD29 (VLA-4) expression. These results suggest that olopatadine may
      inhibit antigen-induced eosinophil infiltration through repression of LFA-1 and
      Mac-1 expression.

PMID- 12046992
TI  - Palliative care in Italy: accident or miracle?

PMID- 12046993
TI  - Current status of hospice cancer deaths both in-unit and at home (1995-2000), and
      prospects of home care services in Japan.
AB  - In Japan, the first government-approved hospice (GAH) and palliative care unit
      was established and commenced operations in 1990, and hospice medical care was
      made eligible for health insurance coverage. By 31 December 2000, the number of
      GAH institutions had increased to 86 (1,590 beds). The ratio of hospices to
      population in Japan is currently approximately 1:1.5 million, with an average of
      one hospice bed for approximately every 80,000 people. This study of institutions
      reports a survey conducted to determine the number of deaths (hospice unit and
      home) of GAH cancer patients, and to determine the servicing status of hospice
      home care for the period 1995 through 2000. The place of death of the patients
      cared for by GAHs in 2000 were: hospice units 97.7% and home 2.3%. GAH patient
      deaths (both inpatient and at home) in 2000 was 2.6% of the total number of
      cancer patients' deaths, an increase of 3.8-fold since 1995. Of the total number
      of GAH institutions, 62% are engaged in home care services and 91 % offer hospice
      care by hospice-assigned doctors. In addition, 72% offer team care with nurses
      based at Home Care Agencies. In order for the hospice (including home care
      service) to become established in a way most appropriate to each region of Japan,
      GAH institutions must assume significant promotional roles in their respective
      regions. One of the goals and assignments of establishing medical service with
      hospice home care in Japan is to develop the systematic care programs of GAH
      institutions, which include home care service in addition to the already
      established hospice unit and outpatient services.

PMID- 12046995
TI  - Decision making in terminal care: a survey of finnish doctors' treatment
      decisions in end-of-life scenarios involving a terminal cancer and a terminal
      dementia patient.
AB  - GOALS: The physicians' decision-making process in terminal care is complex:
      medical, ethical, legal and psychological aspects are all involved, particularly
      in critical situations. Here, a study was made of the association of personal
      background factors with end-of-life decisions. METHODS: A questionnaire was sent
      to 300 surgeons, 300 internists, 500 health centre practitioners (GPs) and all 82
      Finnish oncologists. The response rate was 62%. Two scenarios were presented: one
      involving a terminal cancer patient, the other a dementia patient.
      Sociodemographic factors, general life values and attitudes related to end-of
      life care were asked. MAIN RESULTS: In the cancer case (Scenario 1) 17%, and in
      the dementia case (Scenario 2) 43% of all the respondents chose active treatment.
      In a logistic regression analysis of treatment decisions in Scenario 1,
      physician's age, specialty, marital status and attitudes to assisted suicide and
      withdrawal of life-sustaining treatment (LST) entered the model. In Scenario 2,
      the variables were physician's age, physician's own experience of severe disease
      in the family, attitude to withdrawal of LST and opinion of advanced directives.
      CONCLUSIONS: Doctors' end-of-life decisions vary widely according to personal
      background factors. The findings underline the importance of advance
      communication, making these decisions in accordance with the patient's wishes.

PMID- 12046994
TI  - Family satisfaction with inpatient palliative care in Japan.
AB  - Whereas satisfaction is one of the most important outcomes in palliative care
      settings, there have been no systematic studies investigating the effects of
      family- and organization-related variables on family satisfaction with care. To
      clarify factors contributing to family satisfaction with inpatient palliative
      care services, a cross-sectional mailed survey was performed. A 60-item
      questionnaire was mailed to 1026 bereaved subjects who had lost family members at
      one of 37 palliative care units in Japan to evaluate their sociodemographic
      characteristics and satisfaction levels with care. An institution survey was
      performed to collect organization-related variables. Caregiver satisfaction was
      rated on the Satisfaction scale for Family members receiving Inpatient Palliative
      Care (Sat-Fam-IPC). A total of 640 responses were analysed (response rate = 62%).
      The responses to overall satisfaction were 'satisfied' in 41 % and 'very
      satisfied' in 47%. The mean total score of the Sat-Fam-IPC was 82.4 +/- 13.2 on
      the 0-100 scale. The mean subscale scores were: 85.8 +/- 14.5 (Nursing Care),
      81.5 +/- 18.4 (Symptom Palliation), 85.0 +/- 13.8 (Facility), 83.3 +/- 16.6
      (Information), 83.1 +/- 17.3 (Availability), 78.3 +/- 18.9 (Family Care), and
      79.8 +/- 17.3 (Cost). Significant determinants of family satisfaction identified
      were: nursing system, the number of nurses at night and presence of attending
      medical social workers (Nursing Care), patient age and the number of physicians
      (Symptom Palliation), floor space per bed (Facility), duration of admission and
      presence of attending medical social workers (Availability), patient age, family
      age, gender and occupational status (Family Care), patient age and the extra
      charge for a private room (Cost). In conclusion, informal caregivers are
      generally satisfied with inpatient palliative care services provided by members
      of the Japanese Association of Hospice and Palliative Care Units. The levels of
      satisfaction are influenced by various family- and organization-related
      variables.

PMID- 12046996
TI  - Patient-held records in cancer and palliative care: a randomized, prospective
      trialt.
AB  - OBJECTIVES: To evaluate prospectively the introduction of a patient-held record
      (PHR) in the management of patients with advanced cancer and palliative care
      needs. DESIGN: a) A prospective, parallel group, randomized controlled trial. b)
      A postal survey of the opinions of health professionals whose patients had a PHR.
      SETTING: Out-patient oncology centres in Glasgow and Edinburgh, hospice home-care
      services across the central belt in Scotland. PARTICIPANTS: A total of 244
      patients with advanced cancer recruited either from oncology outpatient clinics
      or hospice home-care services. The baseline interview was completed by 231
      patients and 117 were randomized to receive the PHR. Between 4 and 6 months
      later, 80 patients with the PHR and 97 without were interviewed. Of the 83 health
      professionals caring for patients known to have received the PHR 63 replied to a
      postal questionnaire. MAIN OUTCOME MEASURES: Subjective views of patient
      satisfaction with communication and perception of communication between patient
      and health care professionals as determined by structured interview at baseline
      and after 4-6 months. RESULTS: We could identify no improvement in the provision
      of information to patients, or patients' satisfaction with information provided
      by outpatient doctors, GPs, practice and community nurses and hospice or
      palliative home care staff. Overall, patients' perception of communication
      between all staff involved in their care with and without PHRs was excellent in
      24% and 21 %, respectively, or very good in 56% and 58% (P=0.89). The PHR made no
      difference to information passing between health professionals, or to the degree
      of family involvement. Most of those who had a record found it of some use and
      benefit. CONCLUSION: This study provides no evidence on which to base the
      widespread promotion of PHRs, although local projects with committed clinicians
      and patients may well prove popular and effective.

PMID- 12046997
TI  - The development of clinical guidelines on paracentesis for ascites related to
      malignancy.
AB  - Malignancy-related ascites gives rise to troublesome symptoms and carries a poor
      prognosis. Abdominal paracentesis is a widely used and effective procedure for
      symptom relief, but practice with regard to the procedure itself may vary
      considerably. Evidence obtained in the context of liver disease probably
      influences practice in malignancy, although the pathophysiology involved is
      different. Anecdotal evidence suggested a difference in practice between the
      Exeter and District Hospice and the adjoining hospital, and this was confirmed by
      a review of case notes. Patients undergoing paracentesis in the hospital were
      more likely to have prior ultrasound assessment and to be given intravenous
      fluids, and had longer drainage times and longer inpatient stays. It seemed that
      some practices were placing unnecessary burdens on patients whose life expectancy
      was short. A set of clinical guidelines for the procedure was drawn up, based on
      the limited evidence available and the practice within the hospice. These
      guidelines emphasise performing ultrasound investigations only in cases of
      diagnostic uncertainty, allowing up to 5 L of fluid to drain without clamping,
      leaving drains in for no more than 6 h and giving intravenous fluids only when
      specifically indicated. These guidelines were introduced on the oncology ward of
      the adjoining hospital. The impact on practice was assessed by means of a
      retrospective case note review of all procedures carried out on the ward in the 6
      months before and after the guidelines were introduced. The introduction of
      guidelines resulted in significant reductions in prior ultrasound assessment,
      mean length of time drains were left in and mean length of inpatient stay for
      planned procedures. There were no cases of symptomatic hypotension in the
      postguidelines group.

PMID- 12046998
TI  - Evaluation of the effectiveness of UK community pharmacists' interventions in
      community palliative care.
AB  - INTRODUCTION: In 1997, the Royal Pharmaceutical Society of Great Britain Working
      Party reported that UK community pharmacists had a crucial role in effective
      medicines management and effective symptom control for those receiving palliative
      care in the community. However, prior to the integration of community pharmacists
      into the community palliative team, it is necessary to evaluate the effectiveness
      of their pharmaceutical interventions. AIM: To assess the effectiveness of
      community pharmacists' clinical interventions in supporting palliative care
      patients in primary care using an independent multidisciplinary panel review.
      METHODS: Patients with a life expectancy of less than 12 months were each
      registered with a single pharmacy and their consent was obtained for the
      community pharmacists to access their general practitioner (GP) case records. The
      community pharmacists received training in palliative pharmaceutical care and
      documenting interventions. The trained community pharmacists provided palliative
      pharmaceutical care to the recruited patients. At the end of a 10-month period,
      the clinical interventions were reviewed by an independent multidisciplinary
      expert panel consisting of a palliative care consultant, a Macmillan nurse
      (community palliative care nurse) and a hospital pharmacist with special interest
      in palliative care. RESULTS: Fourteen community palliative care teams (including
      community pharmacists, GPs and community nurses) took part in the study and 25
      patients were recruited over the 10-month recording period. All but one patient
      had a diagnosis of cancer; the other patient had chronic obstructive pulmonary
      disease. By the end of the project, 14 patients had died. Community pharmacists
      recorded a total of 130 clinical interventions. Thirty interventions were
      excluded as insufficient information had been documented to allow review by the
      panel. Eighty-one per cent of the interventions were judged by the expert panel
      likely to be beneficial. However, 3% were judged likely to be detrimental to the
      patients' well-being. CONCLUSIONS: Most of the clinical interventions made by the
      community pharmacists for palliative pharmaceutical care were judged by the
      expert panel as being likely to be beneficial. The result supports the view that
      when community pharmacists are appropriately trained and included as integrated
      members of the team, they can intervene effectively to improve pharmaceutical
      care for palliative care patients.

PMID- 12046999
TI  - The homeopathic approach to symptom control in the cancer patient: a prospective
      observational study.
AB  - The aims of this study were to describe a population of patients with cancer
      referred for complementary therapies to an NHS homeopathic hospital, and to
      explore the homeopathic approach to symptom control and its impact on mood
      disturbance and quality of life. One hundred consecutive patients attending a
      designated research cancer clinic were seen for a consultation, lasting up to 60
      min, and prescription of a homeopathic remedy. A maximum of three symptoms were
      identified and rated by the patient as a problem, using a numerical self-rating
      scale. The effect these symptoms have on daily life and overall sense of well
      being were recorded using similar scales. Patients completed the Hospital Anxiety
      and Depression Scale (HADS) and the European Organization for Research and
      Treatment in Cancer--Quality of Life Questionnaire--Core 30 (EORTC QLQ-30) at the
      initial consultation and at four to six consultations later. After this time, the
      patients completed a final assessment questionnaire asking about satisfaction
      with the homeopathic approach, how helpful they had found the approach for the
      targeted symptoms and what factors they felt may have contributed to the changes
      perceived. One hundred patients were entered into the study. Thirty-nine patients
      had metastatic disease. Nine patients were refusing conventional cancer
      treatments. The most common symptoms were pain, fatigue and hot flushes. Symptom
      scores for fatigue and hot flushes improved significantly over the study period
      but not for pain scores. Side effects included a transient worsening of symptoms
      in a few cases, which settled on stopping the remedy. Fifty-two patients
      completed the study, and in those patients satisfaction was high, and 75% (n=38)
      rated the approach as helpful or very helpful for their symptoms. Results suggest
      that further research is warranted to explore the management of hot flushes in
      women with breast cancer and fatigue in the cancer diagnosis.

PMID- 12047000
TI  - Integration of acupuncture into the oncology clinic.
AB  - PURPOSE/OBJECTIVE: Patients with cancer or symptoms referable to cancer therapy
      were offered acupuncture as potential palliation of their symptoms. This paper
      describes the physical integration of the discipline into the Oncology Clinic,
      and patient perspectives on its availability and efficacy. PATIENTS AND METHODS:
      Between August 1999 and May 2000, 123 patients with varying symptoms received
      acupuncture in our Center's Radiation and Medical Oncology Clinics and Breast
      Health Center. These patients had 823 visits during this time period. A practice
      outcome analysis was performed on patients receiving therapy between 1 January
      2000 and 30 April 2000. The 89 patients treated during this interval had 444
      total visits. In June and July 2000, a questionnaire was administered by phone to
      79 of these patients (89%). Standard allopathic care continued while patients
      were receiving acupuncture. RESULTS: Major reasons for referral included pain
      (53%), xerostomia (32%), hot flashes (6%) and nausea/loss of appetite (6%).
      Patients had a mean of five acupuncture visits (range 1-9). Most patients (60%)
      showed at least 30% improvement in their symptoms. About one-third of patients
      had no change in severity of symptoms. There were no untoward effects reported
      related to the acupuncture. When analysed by diagnosis, these values persist.
      Irrespective of response to therapy, 86% of respondents considered it 'very
      important' that we continue to provide acupuncture services. CONCLUSION:
      Acupuncture may contribute to control of symptoms for cancer patients. Expansion
      of providers, continued patient follow-up, optimization of techniques and
      prospective objective measurement of response continue in our clinic.

PMID- 12047001
TI  - How and why do GPs use specialist palliative care services?
AB  - This study presents findings on the interaction of generalists and specialists
      within palliative care. General practitioners (GPs) are central to community
      palliative care as most of the last year of a patient's life is spent at home
      under the care of the primary health care team. GPs see few palliative care
      patients each year, however, and access to specialist palliative care services
      for support, advice and referral can be important particularly to support
      patients who wish to die at home. The aim of this study was to explore GP use of
      and attitudes towards specialist palliative care services through semi-structured
      interviews in inner city, urban and rural areas. It was part of a longitudinal
      evaluation of an educational intervention, and the quantitative components are
      reported elsewhere. Sixty-three GPs were interviewed, having been sampled
      randomly from inner city, urban and rural health authority district lists. While
      most interviewees reported using specialist palliative care services as a
      resource, other models of use included working together as an extended team,
      seldom using such services and handing over care or responsibility entirely.
      Availability of services clearly shaped use, but previous experience and
      expectations of easy access were also important. Patterns of use were not
      necessarily fixed, but dependent also on the differing needs of and wishes of
      patients and carers. Specialist palliative care services need to be aware of such
      variations in ways of working and to consider the implications for the capacity
      and flexibility of both primary care and specialist service provision.

PMID- 12047002
TI  - Defining patients as palliative: hospital doctors' versus general practitioners'
      perceptions.
AB  - There appears to be a lack of consensus on the classification of individual
      patients as 'for palliative care', although the extent of this is unknown.
      General practitioners (GPs) of 213 patients with a palliative diagnosis of lung
      or colo-rectal cancer were sent a one-page questionnaire to assess information
      sent by hospital doctors, and to establish the GPs' perception of patients'
      palliative status. A total of 185 questionnaires were returned (87% response
      rate). Of those GPs receiving information from the hospital, one in four rated
      the adequacy as less than positive; 26% reportedly received no information or
      received it 'too late'. In 20% of cases, GPs did not perceive patients as
      palliative, although hospital records suggested that they were, and death
      certificates received later potentially confirmed this. There was, however, no
      significant difference between GPs allocating a patient to palliative status or
      not, in terms of the promptness or adequacy of information received from the
      hospital, as rated by the GP. There was a significant difference in survival
      between patients whom GPs perceived as for palliative care and those they did not
      ('palliative' patients died, on average, 117 days earlier). Possible explanations
      of the differing perceptions of patients' palliative status are discussed. The
      findings have implications for patient care in the community, patients' informed
      choices, and palliative care research.

PMID- 12047003
TI  - General practitioners' and district nurses' views of hospital at home for
      palliative care.
AB  - Cambridge Hospital at Home (CH@H) provides 24-h nursing in a patient's own home
      to patients requiring terminal and palliative respite care. To investigate views
      of the service, we surveyed all GPs and district nurses (DNs) in the catchment
      area of the scheme. Responses were received from 85% of DNs and 65% of GPs. The
      majority of DNs (93%) and GPs (57%) had patients referred to CH@H, whereas 90% of
      DNs and 42% GPs had patients admitted. The most commonly reported reason for non
      referral was lack of availability of places (GPs 62%; DNs 63%). Ninety per cent
      DNs and 84% GPs rated continuation of the scheme as important. The most important
      reported benefits were 24-h care (GPs 84%; DNs 82%) and help in keeping patients
      at home (GPs 69%; DNs 83%). Seventy-four DNs also considered help in arranging
      discharge to be important. Almost half GPs and DNs considered CH@H worse than
      other NHS services in terms of availability and limits on the duration of care.
      Whilst 65% of DNs thought CH@H had reduced workload, 77% GPs reported it had made
      no difference or had increased it. Most indicated that CH@H made a difference in
      allowing patients to die at home (GPs 60%; DNs 68%). The CH@H scheme is viewed as
      beneficial for patients requiring palliative care at home, although GPs and DNs
      expressed realistic reservations about specific aspects of the scheme. With the
      emergence of Primary Care Trusts, NHS commissioning of hospice at home services
      will more firmly rest with primary care practitioners, who on balance clearly
      prize them.

PMID- 12047004
TI  - Population-based trends in referral of the elderly to a comprehensive palliative
      care programme.

PMID- 12047005
TI  - Nitrous oxide is not beneficial for breakthrough cancer pain.

PMID- 12047006
TI  - Efficacy of methylphenidate for fatigue in advanced cancer patients: a
      preliminary study.

PMID- 12047007
TI  - Deciding upon and refining a research question.

PMID- 12047008
TI  - Editor's introduction: antipsychotic prescribing practices.
AB  - This commentary is an introduction to a set of articles reviewing antipsychotic
      prescribing practices for individuals with schizophrenia, noting where these
      practice patterns conform to or deviate from evidence-based practice, and
      identifying the pressing research questions raised by these variations. The
      delineation of practices supported by the evidence base is crucial for the
      practical concerns of creating practice guidelines and monitoring performance, as
      well as for identifying areas where the reach of clinical practice must exceed
      the grasp of current knowledge. These gaps in knowledge should guide the
      development of a research agenda that addresses pressing questions commonly
      confronted in everyday practice. We know from the Schizophrenia Patient Outcomes
      Research Team (PORT) project and other surveys that clinically significant
      research findings are not making their way into practice. Additionally, as the
      articles assembled here indicate, questions of pressing importance in routine
      practice have yet to make their way into research agendas.

PMID- 12047009
TI  - Combination antipsychotics: pros, cons, and questions.
AB  - In prescription surveys, use of combination antipsychotics is common and is
      increasing, despite little supporting evidence. This article highlights potential
      problems with using combination antipsychotics, discusses paths to their
      maintenance use, and reviews the efficacy evidence. Paths to maintenance
      antipsychotic combinations include (1) failure or patient refusal of all
      reasonable monotherapies, (2) indefinite continuation of combinations initially
      intended to be brief, (3) trials of combinations in preference to reasonable
      monotherapy trials, and (4) addition of a second antipsychotic to counteract a
      problem (safety, tolerability, or adherence) arising during successful
      monotherapy. Virtually all of the evidence on combination antipsychotics is on
      augmentation of clozapine, with only one randomized controlled trial. Research on
      combination antipsychotics is sorely needed. Designing clinical trials is made
      difficult by the very large numbers of possible combinations and doses. It may be
      feasible to analyze existing data bases to identify combinations that appear
      particularly promising to investigate.

PMID- 12047010
TI  - "Real world" atypical antipsychotic prescribing practices in public child and
      adolescent inpatient settings.
AB  - This article examines the factors that influence antipsychotic use among youth
      treated in public inpatient facilities. By combining data from 11 focus groups, a
      survey of 43 researchers and clinicians, and a chart review of 100 closed patient
      charts, we investigated the interplay between physicians' and staff members'
      perceptions of problems related to antipsychotic prescribing, their beliefs
      concerning optimal approaches, their actual recorded prescribing behaviors, and
      the discrepancies between their beliefs and their recorded practices. We
      discovered that antipsychotics are prescribed broadly to treat a variety of
      conditions, including nonpsychotic disorders among children in public inpatient
      facilities. Despite overall expert consensus regarding "best practices,"
      physicians described systemic obstacles that prevent the application of these
      practices, and our data confirmed that best practices are not always followed.
      Future research should be done with this patient population and should
      investigate the factors that influence antipsychotic use among inpatient youth.

PMID- 12047011
TI  - Helping clozapine help: a role for support groups.
AB  - A successful clozapine support group operates from the principle that the drug is
      most successful when the person takes it as prescribed. The likelihood of initial
      and ongoing collaboration with treatment is increased when the tangible gains of
      the treatment can be experienced in the self and demonstrated in others.
      Clozapine support groups can advance the goals of collaboration and recovery.

PMID- 12047012
TI  - Can clinical practice guide a research agenda?
AB  - Articles from this issue of the Bulletin indicate that clinicians are frequently
      adopting clinical practices that have not been supported by an evidence base.
      Examples of these practices are prescribing more than one antipsychotic and
      reserving clozapine for patients who have had multiple antipsychotic trials. This
      commentary suggests that these practices can be used to define important research
      questions.

PMID- 12047013
TI  - Attributional style in schizophrenia: an investigation in outpatients with and
      without persecutory delusions.
AB  - The attributional style of outpatients with schizophrenia with and without
      persecutory delusions was investigated. Thirty individuals with schizophrenia
      were divided into persecutory-deluded and non-persecutory-deluded groups based on
      a score of 5 or higher on the suspiciousness item from the Expanded Brief
      Psychiatric Rating Scale (BPRS-E). The two resulting groups, and a nonclinical
      control group, were administered a battery of attributional measures, and their
      attributional responses were coded by both the subjects themselves and a pair of
      independent raters. The results showed evidence of a self-serving bias for
      subjects with persecutory delusions; however, this bias was not unique to those
      with persecutory delusions, and it disappeared when independent raters evaluated
      subjects' causal statements on a reliable measure of attributional style.
      Subjects with persecutory delusions tended to show a stronger bias toward blaming
      others rather than situations for negative outcomes, and there was a linear
      association between persecutory ideation and a self-serving attributional style.
      Finally, there were significant discrepancies between the attributional ratings
      of the persecutory-deluded subjects and those of independent judges. Implications
      for future research are discussed.

PMID- 12047014
TI  - Experiences of stigma among outpatients with schizophrenia.
AB  - Many individuals with schizophrenia are devalued and discriminated against
      because of their mental illness. There has been only limited study of how
      individuals with schizophrenia experience mental illness stigma. We evaluated 74
      stable outpatients with schizophrenia receiving community care. Study
      participants were interviewed with the Consumer Experiences of Stigma
      Questionnaire (CESQ), the Positive and Negative Syndrome Scale, and several
      social functioning measures. On the CESQ, all but one respondent indicated having
      at least one stigma experience. The most frequently reported CESQ items were
      respondents' worry about being viewed unfavorably because of their psychiatric
      illness (70%) and avoidance of telling others about it (58%). Many respondents
      also indicated having heard offensive statements (55%) and media accounts (43%)
      about persons with psychiatric disorders. Socioeconomic variables, but not
      symptoms or social functioning measures, were related to the extent of stigma and
      discrimination experiences. These results document the extent to which persons
      with mental illness experience negative reactions from others. Strategies are
      needed to enhance how persons with schizophrenia cope with stigma.

PMID- 12047015
TI  - Premorbid adjustment and neuropsychological performance in schizophrenia.
AB  - To examine the relationship between premorbid adjustment and neuropsychological
      deficit in schizophrenia, this report examined retrospective ratings of social
      and school adjustment during three age epochs (childhood, early adolescence, and
      late adolescence) as predictors of neurocognitive performance in 61 clinically
      and pharmacologically stabilized schizophrenia outpatients. Results indicated
      greater cognitive deficits when premorbid adjustment was unfavorable,
      particularly for measures of attention and executive functions. Premorbid number
      and quality of peer relationships and psychosocial adaptation to the school
      environment were more closely related to neuropsychological performance during
      adulthood than were premorbid withdrawal and premorbid academic performance.
      Early onset of poor premorbid adjustment rather than deterioration from childhood
      to adolescence was associated with greater neuropsychological disturbance in
      adulthood. It is suggested that childhood onset of premorbid deficits in
      selective areas of social and academic adjustment appears to influence the
      cognitive performance seen in adult schizophrenia. This study is consistent with
      findings from other related reports; it extends these findings to a larger and
      clinically stabilized sample.

PMID- 12047016
TI  - A controlled trial of cognitive remediation in schizophrenia.
AB  - A randomized, controlled trial of a 3-month cognitive remediation program was
      examined for its efficacy at ameliorating deficits in social and emotion
      perception in 42 hospitalized patients with schizophrenia. Generalization of
      training effects to attention, memory, and executive functioning was also
      examined. The program included an eclectic mix of self-instruction, memory
      enhancement, inductive reasoning, and compensatory training procedures, while the
      control condition included participation in a leisure group that was matched to
      the experimental group for staff involvement time. Patient care management,
      including type and dose of antipsychotic medication, remained constant throughout
      the study period. The results indicated that the cognitive training program
      improved emotion perception, with some evidence of generalization to measures of
      executive functioning; other areas of neurocognitive functioning were largely
      unaffected. While cognitive training programs may improve targeted areas of
      neurocognitive processing, broad generalization effects to domains outside those
      targeted for intervention are not likely concomitants.

PMID- 12047018
TI  - Response to "The prevention of schizophrenia: what interventions are safe and
      effective?".

PMID- 12047017
TI  - Antipsychotic prescribing practices in Connecticut's public mental health system:
      rates of changing medications and prescribing styles.
AB  - We characterized prescribing in Connecticut's State public mental health system
      to assess the feasibility of implementing an evidence-based medication algorithm.
      Medication records for a random sample of outpatients with diagnoses of
      schizophrenia spectrum disorders showed prescribing patterns similar to the
      entire United States. The base rate of changing antipsychotic medications was
      moderate. Over half of patients received decanoate medications, polypharmacy was
      nontrivial, and there was variability in prescribing patterns across physicians.
      Caucasian patients were more likely to receive an atypical antipsychotic and less
      likely to have a decanoate medication, and Latino patients were less likely to
      change medications. Because the base rate of changing medications was moderate
      and a considerable proportion of patients were prescribed newer antipsychotic
      medications, introducing a research-derived medication algorithm with newer
      atypical antipsychotics as first line agents may fit well with current practice.
      Further, implementing such an algorithm may reduce racial and ethnic disparities
      in prescribing patterns.

PMID- 12047019
TI  - First person account: Susan's cello.

PMID- 12047020
TI  - Antipsychotic prescribing practices in the Veterans Healthcare Administration-
      New York metropolitan region.
AB  - Most research literature concerning pharmacological treatments reports results
      from controlled clinical trials, which provide data critical to assess the
      efficacy of new treatments in research populations. Fewer studies examine how
      treatments are adopted in everyday practice settings, where comorbid disorders
      and environmental issues typically complicate patients' situations. In this
      study, we examine the evolution of antipsychotic prescribing practices in the New
      York region of the Veterans Healthcare Administration (VHA) from 1998 to 2000
      using administrative data. Second generation antipsychotic medications are now
      prescribed more frequently than the older antipsychotic medications, with a
      concomitant increase in cost. Data show low rates of clozapine use, relatively
      high rates of polypharmacy, and intersite variation in prescribing practices.
      Additional research in everyday practice settings is needed to address clinical
      questions unlikely to be answered through traditional efficacy research and to
      examine reasons for intersite differences in prescribing patterns.

PMID- 12047021
TI  - Clinical profile of an atypical antipsychotic: risperidone.
AB  - Stimulated by Dawkins and colleagues' (1999) and Remington and Kapur's (2000)
      calls to develop clinical profiles of the new atypical antipsychotic drugs and by
      Mattes's critiques (1997, 1998), we performed two sets of analyses for
      risperidone. First, we reanalyzed data from the North American risperidone trial:
      risperidone was superior to haloperidol to an equal degree in patients with and
      without the deficit syndrome, in patients with paranoid and nonparanoid
      schizophrenia, in treatment-resistant and treatment-responsive patients (patients
      hospitalized for longer and shorter periods), and in patients with or without
      weight gain. Moreover, risperidone was more effective than haloperidol on
      symptoms nonresponsive and responsive to haloperidol; its effects on negative
      symptoms were independent of its effects on extrapyramidal symptoms; and it was
      effective in treating depression in schizophrenia. Second, we performed a meta
      analysis of 18 controlled risperidone trials: risperidone was consistently more
      effective than conventional antipsychotics in treating positive and negative
      symptoms.

PMID- 12047022
TI  - The Mount Sinai conference on the pharmacotherapy of schizophrenia.
AB  - This report summarizes the recommendations from a consensus meeting that focused
      on specific questions regarding the pharmacotherapy of schizophrenia. The issues
      were selected because there was evidence that experts had recently disagreed
      about the evidence supporting a particular practice or when there were
      substantial variations in a clinical practice indicating that there was
      disagreement among clinicians. The group of experts was able to reach a consensus
      regarding the evidence base pertaining to the following issues: First generation
      (FGAs) and second generation (SGAs) antipsychotics as first line agents; the
      duration of antipsychotic trials; the effectiveness of clozapine and other agents
      for treatment refractory schizophrenia; risk of tardive dyskinesia on FGAs and
      SGAs; differences among antipsychotics for different dimensions of
      psychopathology; and side effect monitoring for various antipsychotics.

PMID- 12047023
TI  - The schizophrenia PORT pharmacological treatment recommendations: conformance and
      implications for symptoms and functional outcome.
AB  - This cross-sectional study examines conformance to four of the Schizophrenia
      Patient Outcomes Research Team (PORT) antipsychotic treatment recommendations,
      patient and treatment setting characteristics assocated with conformance, and the
      relationship of conformance with outcome. Two hundred twenty-four inpatients and
      358 outpatients with schizophrenia underwent an interview and review of their
      medical records. Demographic, clinical, and role function data were collected.
      Almost all inpatients and outpatients with schizophrenia or schizoaffective
      disorder were prescribed an antipsychotic. The majority of inpatients were
      prescribed an antipsychotic within the recommended dose range, whereas the
      majority of outpatients were prescribed an antipsychotic either below or above
      the recommended dose range. There were no consistent relationships between
      patient, geographic, and treatment characteristics and antipsychotic dose.
      Patients treated with conventional antipsychotic doses below the recommended dose
      range had significantly better role function. Prospective longitudinal studies
      are required to delineate the factors that may underlie this relationship.

PMID- 12047024
TI  - Recent trends in antipsychotic combination therapy of schizophrenia and
      schizoaffective disorder: implications for state mental health policy.
AB  - Little is known about antipsychotic combination therapy, although this practice
      is becoming increasingly common in the treatment of schizophrenia. Medicaid
      pharmaceutical claims for a cohort of 836 New Hampshire beneficiaries with
      schizophrenia or schizoaffective disorder were followed from 1995 through 1999.
      Use of traditional and atypical antipsychotic medications, antidepressants,
      anxiolytic hypnotics, and mood stabilizers was tracked monthly. The number of
      medications, frequency of coprescription, and Medicaid pharmaceutical costs are
      described. The proportion of individuals with schizophrenia and schizoaffective
      disorder treated with atypical antipsychotics grew from 43 percent in 1995 to 70
      percent in 1999. At the same time, concurrent use of two or more antipsychotic
      medications quadrupled, increasing from 5.7 percent to 24.3 percent. Persons with
      schizophrenia were also prescribed more antidepressants (increased from 18.5% in
      1995 to 35.6% in 1999), anxiolytics (increased from 19.9% to 33.5%), and mood
      stabilizers (increased from 17.7% to 30.0%). The increase in multiple agent
      therapy appears to be broad-based. Data are needed on the effectiveness and cost
      effectiveness of these practices to inform clinical decision making and health
      policy.

PMID- 12047025
TI  - Using state administrative and pharmacy data bases to develop a clinical decision
      support tool for schizophrenia guidelines.
AB  - Administrative and pharmacy data bases represent a largely untapped resource for
      clinical decision support and quality improvement. In this study, we examined the
      feasibility of using New York State Office of Mental Health (NYSOMH) data bases
      to develop an automated clinical report to support implementation of
      schizophrenia guidelines. First we reviewed the structure of existing data bases
      for capacity and limitations in supporting guideline implementation. Second, we
      identified schizophrenia guideline recommendations and adherence measures that
      would be the focus of our implementation. Third, a preliminary report was
      programmed, based on operational definitions of the guideline recommendations.
      Finally, we developed user groups to define content and format of new reports,
      through an iterative process of field testing, feedback, and revision. Our
      experience suggests that administrative and pharmacy data bases, despite their
      limitations, can be used to develop guideline-based clinical decision support
      tools for schizophrenia with high physician acceptability.

PMID- 12047026
TI  - Process measures for the assessment and improvement of quality of care for
      schizophrenia.
AB  - The development of process measures for the assessment and improvement of care
      for schizophrenia is at an early stage. As part of a national inventory of mental
      health quality measures, we identified 42 process measures developed to assess
      the quality of schizophrenia care. A greater proportion of measures assessed
      pharmacotherapy than assessed psychosocial interventions or other clinical
      processes, such as assessment, continuity, or coordination. Twenty-five measures
      (60%) were based on research evidence linking measure conformance with improved
      patient outcomes, while 17 (40%) were based on clinical consensus or opinion.
      Only 12 measures (29%) were fully operationalized. Few were tested for validity
      or reliability. A number of demonstration projects currently under way should
      expand the pool of well-developed and tested measures. Further research and
      consensus development will be needed to identify common measurement priorities,
      reduce the data collection burden, enhance the interpretability of results, and
      allow for comparisons of clinical practice across facilities and health care
      systems.

PMID- 12047028
TI  - Effects of hormone replacement therapy on left ventricular hypertrophy and growth
      promoting factors in hypertensive postmenopausal women.
AB  - We investigated the effects of hormone replacement therapy (HRT) on left
      ventricular hypertrophy (LVH) and growth-promoting factors in hypertensive
      postmenopausal women (PMW) with LVH. Twenty-one Japanese hypertensive PMW (age
      55.3+/-0.8 years) with LVH who had never received HRT volunteered to participate
      in this study. Eleven subjects received a daily dose of HRT (0.625 mg conjugated
      equine estrogen, 2.5 mg medroxyprogesterone acetate) orally for 12 months. Ten
      PMW who refused HRT were enrolled as controls. Blood pressure and serum
      angiotensin-converting enzyme (ACE) activity, plasma aldosterone, and insulin
      resistance were measured. M-mode echocardiography and blood pressure measurements
      were performed in all patients. Data obtained before and after 12 months of HRT
      were compared. No significant differences in blood pressure were observed between
      the two groups after 12 months of HRT. In the HRT group, the LV mass index
      (p<0.01), serum ACE activity (p<0.01), and plasma aldosterone (p<0.01) levels
      were reduced after 12 months of treatment. The changes in serum ACE activity and
      plasma aldosterone were not correlated with the change in LV mass index in the
      HRT group. No significant changes in blood pressure, LV mass index, serum ACE
      activity, plasma aldosterone, or insulin resistance were observed in the control
      group. HRT contributed to the reduction of LV mass in hypertensive PMW. However,
      the effect of HRT on LVH did not appear to be associated with changes in growth
      promoting factors, such as blood pressure, serum ACE activity, plasma
      aldosterone, and insulin resistance.

PMID- 12047027
TI  - New diagnostic procedure for primary aldosteronism: adrenal venous sampling under
      adrenocorticotropic hormone and angiotensin II receptor blocker--application to a
      case of bilateral multiple adrenal microadenomas.
AB  - Formerly, the incidence of primary aldosteronism (PA) among patients with
      hypertension was believed to be less than 1%. However, recent studies have
      suggested a much higher incidence of 6.59%-14.4% among such patients. These
      findings suggest that many cases of PA caused by small aldosterone-producing
      adenoma (APA) or idiopathic hyperaldosteronism (IHA) have not been properly
      diagnosed. To make a more accurate diagnosis in such cases, we developed a new
      diagnostic procedure for localization of PA, namely, adrenal venous sampling
      under continuous infusion of adrenocorticotropic hormone (ACTH) and
      administration of angiotensin II receptor blocker (AVS with ACTH and ARB). Here,
      we confirm the efficacy of this procedure in the case of a 37-year-old male
      suspected of having PA. The anticipated diagnosis of PA was based on the presence
      of hypokalemia, low plasma renin activity (PRA), elevated plasma aldosterone
      concentration (PAC) and left adrenal mass. However, AVS with ACTH and ARB
      revealed the presence of bilateral multiple adrenal microadenomas. In the new AVS
      method, neither ACTH nor the renin-angiotensin system (RAS) exert any influence
      on the plasma aldosterone level, and a more accurate aldosterone secretary state
      and a more accurate assessment of the aldosterone secretion of both adrenal
      glands can be recognized than by conventional AVS. Use of this new method should
      enable identification of additional cases of APA among patients diagnosed with
      essential hypertension.

PMID- 12047029
TI  - Leptin causes vasodilation in humans.
AB  - Leptin, a product of the ob gene, plays an important role in the regulation of
      body fat and has been suggested to cause vasodilation in rats. The purpose of
      this study was to evaluate whether leptin also has a vasodilating effect in
      humans. Using a strain-gauge plethysmography, we evaluated forearm blood flow
      (FBF) during intra-arterial infusion of leptin (1, 10 or 100 ng/kg/min for 5 min)
      in the absence and presence of the nitric oxide synthase inhibitor N(G)
      monomethyl-L-arginine (L-NMMA; 8 micromol/min for 5 min) in ten healthy men (mean
      age, 23.0+/-1.2 years). Leptin infusion significantly increased the FBF (8.5+/
      3.8, 20.3+/-7.0 and 17.7+/-5.4% at 1, 10 and 100 ng/kg/min of leptin,
      respectively; p<0.05) and the forearm vascular resistance (FVR; -6.9+/-3.1, 
      14.6+/-4.3 and -13.4+/-3.9% at 1, 10 and 100 ng/kg/min of leptin, respectively;
      p<0.05). No significant changes in blood pressure or heart rate were detected
      during infusion of leptin. The intra-arterial infusion of L-NMMA did not alter
      the FBF response (6.6+/-4.9, 22.1+/-7.5, 13.3+/-3.2% at 1, 10 and 100 ng/kg/min
      of leptin, respectively) or the FVR response (-4.3+/-4.6, -15.2+/-5.4, -11.1+/
      2.5% at 1, 10 and 100 ng/kg/min of leptin, respectively) to leptin. These
      findings suggest that leptin per se directly causes vasodilation and that leptin
      induced vasodilatation is nitric oxide-independent in healthy men.

PMID- 12047030
TI  - Relationship between home blood pressure and longitudinal changes in target organ
      damage in treated hypertensive patients.
AB  - Cross-sectional studies have shown that home blood pressure (BP) correlates with
      hypertensive target organ damage better than clinic BP. However, there have been
      few longitudinal studies regarding the predictive value of home BP on the changes
      in organ damage in treated hypertensive patients. Clinic and home BP over a 12
      month period, antihypertensive medication use, echocardiographic and
      electrocardiographic results, and serum creatinine and urinary protein levels
      were examined in 209 treated hypertensive patients in 1993. These patients were
      prospectively followed for 5 years. The patients were divided into 4 subgroups
      according to hypertension control as follows: good control (<140/90 mmHg for
      clinic BP, <135/85 mmHg for home BP), improved, worsened, and poor control. The
      average clinic BP was 147.0+/-14.9/87.0+/-7.6 mmHg (mean+/-SD) in 1993 and
      146.0+/-13.7/84.1+/-7.5 mmHg in 1998. The average home BP was 136.8+/-10.4/84.3+/
      7.6 mmHg in 1993 and 136.1+/-9.7/81.2+/-7.7 mmHg in 1998. The left ventricular
      mass index (LVMI) positively correlated with both home systolic BP and clinic
      systolic BP in 1998 but not in 1993. The correlation tended to be closer for home
      BP than for clinic BP. LVMI did not change in patients with good or improved home
      systolic BP, while it increased in those with poor or worsened home systolic BP.
      The relationship between changes in LVMI and clinic BP was not significant. In
      conclusion, Home BP was more effective than clinic BP as a predictor of changes
      in left ventricular hypertrophy in treated hypertensive patients. Home BP should
      be controlled to below 135/85 mmHg to prevent cardiac hypertrophy.

PMID- 12047031
TI  - Trends in pharmacologic management of hypertension in Japan one year after the
      publication of the JSH 2000 guidelines. First Japanese Society of Hypertension.
AB  - Hypertension, a major risk factor for cerebrovascular disease and heart disease,
      often requires drug therapy. The First Japanese Society of Hypertension
      Guidelines for the Management of Hypertension were published in June 2000. In the
      present work, we surveyed 447 doctors who attended continuing medical education
      meetings between March and July 2001 to elucidate national antihypertensive
      treatment patterns. A minimum level of 150/95 mmHg was selected by 60% and 140/90
      mmHg by 19% of respondents as thresholds for initiating drug treatment, while
      130/85 mmHg was selected by 26% of respondents as the goal blood pressure in
      middle-aged uncomplicated male patients. Sixty-nine percent of respondents
      selected a calcium antagonist as their previous drug of the first choice and 22%
      selected an ACE inhibitor. For their future first choice, 55% would prescribe an
      angiotensin II receptor antagonist (AIIA); 19% an ACE inhibitor; and 16% a
      calcium antagonist. Seventy-two percent selected a calcium antagonist + an ACE
      inhibitor and 17% selected a calcium antagonist + AIIA as their previous first
      choice drug combinations. For their future drug combinations, 56% would select an
      AIIA + a calcium antagonist and 25% a calcium antagonist + an ACE inhibitor. Four
      weeks or less was selected by 69% of respondents as the period intended to reach
      the goal blood pressure. Eight weeks or more was selected by 28%. Overall, our
      data suggest that doctors in Japan are still cautious and conservative in
      controlling blood pressure levels but want rapid achievement of the goal blood
      pressure. Their first choice drug is shifting from calcium antagonists to AIIAs.
      These findings indicate the need for continued effort to evaluate the diversity
      of clinical practice and assess the appropriateness of continuing medical
      education.

PMID- 12047032
TI  - Association of a mast cell chymase gene variant with HDL cholesterol, but not
      with blood pressure in the Ohasama study.
AB  - Two enzymes, chymase and angiotensin converting enzyme (ACE), are involved in the
      production of angiotensin II. Our previous study revealed the male-specific
      effect of the ACE DD genotype on the risk for hypertension, but the genetic role
      of chymase remains unclear. In the present study, we report the results of an
      association study involving 1,046 subjects recruited from a general population in
      Ohasama, a rural community in the northern part of Japan. In addition to casual
      blood pressure (casual BP) measurement, home BP measurements were obtained from
      all participants. There were no differences in either home or casual BP values
      according to G3255A polymorphism of the mast cell chymase gene (MCC). HDL
      cholesterol level was significantly higher among carriers of the A3255 allele
      (p<0.04). After adjustment for confounding factors, the A3255 allele was still
      shown to have an effect on HDL cholesterol metabolism (p<0.03). Multiple
      regression analysis showed that MCC polymorphism was significantly and
      independently related to serum HDL cholesterol level. In conclusion, G3255A
      polymorphism of MCC is not directly associated with blood pressure but may
      modulate the prevalence of hypertensive complications via alteration of lipid
      metabolism.

PMID- 12047033
TI  - Prevalence and correlates of diabetes mellitus in a screened cohort in Okinawa,
      Japan.
AB  - The incidence of end-stage renal disease due to diabetes mellitus (DM) is
      increasing. There have been too few epidemiological studies of the predictors of
      DM nephropathy, particularly type 2 DM, among a statistically significant
      population. We studied the prevalence and correlates of DM in a screened cohort
      in Okinawa, Japan. A total of 9,914 screenees (6,163 men and 3,751 women) over 18
      years of age underwent a 1-day health check at the Okinawa General Health
      Maintenance Association between April 1997 and March 1998. Subjects were
      considered to have DM if they showed a fasting plasma glucose > or = 126 mg/dl
      and hemoglobin A1c > or = 7.0%, or if they were receiving treatment for DM. Non
      DM subjects were followed-up until March 2000 to see whether or not they
      developed DM. Relative risk for developing DM was evaluated by Cox proportional
      hazard analysis after adjusting for confounding variables. A total of 673
      screenees (520 men and 153 women) were diagnosed with DM. The prevalence of DM
      was 67.9 per 1,000 screenees (84.4 for men and 40.8 for women). A total of 7,125
      non-DM screenees were examined a second time. Among them, 164 screenees (130 men
      and 34 women) had developed DM during the follow-up period. Over 2 years, the
      cumulative incidence of DM was 2.3% (2.9% in men and 1.3% in women). The adjusted
      relative risk (95% confidence interval) for developing DM was highest for
      proteinuria, or 1.90 (1.14-3.17). The results indicated that the prevalence and
      incidence of DM were high among this screened cohort in Okinawa, Japan. Subjects
      with proteinuria may thus be at high risk for developing DM.

PMID- 12047034
TI  - The relation between left ventricular geometric patterns and left ventricular
      midwall mechanics in hypertensive patients.
AB  - To evaluate the alteration of myocardial contractility in hypertensive patients
      with different left ventricular geometric patterns by the end-systolic stress
      midwall fractional shortening relation. Echocardiography was applied to study the
      left ventricular geometry and cardiac function among 117 cases of essential
      hypertension, with 45 normal cases as control(s). Left ventricular mass index
      (LVMI) and relative wall thickness (RWT) were calculated using echocardiographic
      data. All patients were divided into four kinds of left ventricular geometry
      pattern based on LVMI and RWT. Patients of the eccentric hypertrophy group
      suffered the most serious damage of left ventricular systolic function.
      Myocardial contractility shown by end-systolic stress-midwall fractional
      shortening relation was significantly decreased in the concentric remodeling
      group, eccentric hypertrophy group and concentric hypertrophy group, and those
      with concentric hypertrophy showed the worst contractility. The degree of
      myocardial contractility damage was different in patients with different left
      ventricular geometric patterns. Geometric changes may have compensated for the
      reduction of myocardial contractility in some phases in order to maintain the
      normal pump function.

PMID- 12047035
TI  - Impaired endothelial alpha-2 adrenergic receptor-mediated vascular relaxation in
      the fructose-fed rat.
AB  - To investigate the vascular endothelial dysfunction in the insulin resistance
      syndrome, muscarinic and alpha2-adrenergic mediated relaxations were studied in
      the fructose-fed rat. Male Sprague-Dawley rats were fed either fructose-rich chow
      (FFR, n=14) or normal chow (CNT, n=13) for 8 weeks. Systolic blood pressure (SBP)
      was measured by the tail-cuff method. A 3 mm segment of mesenteric artery was
      cannulated and pressurized, pretreated with prazosin (10(-6) mol/l) and
      propranolol (3x10(-6) mol/l), then pre-contracted with serotonin (10(-6) mol/l).
      Endothelium-dependent relaxation was induced by addition of acetylcholine (ACh,
      10(-9)-10(-4) mol/l) or a selective alpha2-agonist, B-HT 920 (10(-9)-10(-5)
      mol/l), with or without the nitric oxide (NO) synthase inhibitor, L-NAME (10(-4)
      mol/l). SBP was significantly elevated in FFR but not in CNT. Plasma triglyceride
      in FFT (241+/-115 mg/dl) was significantly (p<0.01) higher than in CNT (84+/-34
      mg/dl). Insulin and insulin/glucose ratio were higher but not significantly.
      Plasma glucose was not different between the two groups. In the dose-response
      curves to ACh, maximum relaxation and ED50 were similar between FFR and CNT.
      Moreover, L-NAME shifted the dose-response curves similarly to the right in both
      groups. Dose-response curves to B-HT 920, however, showed less relaxation in FFR
      than in CNT (p<0.05). B-HT 920-induced relaxations were mostly abolished by L
      NAME. It is concluded that endothelial alpha2-adrenergic relaxation,
      predominantly mediated by NO, is likely more sensitive to the development of
      insulin resistance than muscarinic receptor relaxation in this 8-weeks FFR model.
      This early impairment of endothelial alpha2-adrenergic relaxation may contribute
      to the development of hypertension and insulin resistance in the FFR.

PMID- 12047036
TI  - Effects of an HMG-CoA reductase inhibitor in combination with an ACE inhibitor or
      angiotensin II type 1 receptor antagonist on myocardial metabolism in ischemic
      rabbit hearts.
AB  - We investigated the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor, pravastatin, an angiotensin converting enzyme (ACE)
      inhibitor, temocaprilat, and an angiotensin II type 1 (AT1) receptor antagonist,
      CV-11974, on myocardial metabolism during ischemia in isolated rabbit hearts
      using phosphorus 31-nuclear magnetic resonance (31P-NMR) imaging. Forty-five
      minutes of continuous normothermic global ischemia was carried out. Pravastatin,
      temocaprilat, CV-11974 or a nitric oxide synthase inhibitor, L-NAME was
      administered from 60 min prior to the global ischemia. Japanese white rabbits
      were divided into the following experimental groups, a control group (n=7), a
      group treated with pravastatin (P group; n=7), a group treated with pravastatin
      and temocaprilat (P+T group; n=7), a group treated with pravastatin and CV-11974
      (P+CV group; n=7), and a group treated with pravastatin and L-NAME (P+L-NAME
      group; n=7). During ischemia, P group, as well as either P+T group or P+CV group,
      showed a significant inhibition of the decreases in adenosine triphosphate (ATP)
      and intracellular pH (pHi) (p<0.01, respectively, at the end of ischemia compared
      to the control group as well as P+L-NAME group), and a significant inhibition of
      the increase in inorganic phosphate (Pi) (p<0.01, respectively, compared with the
      control group as well as P+L-NAME group). These results suggest that pravastatin
      significantly improved myocardial energy metabolism during myocardial ischemia.
      This beneficial effect was dependent on NO synthase. However, this beneficial
      effect was not enhanced by either temocaprilat or CV-11974.

PMID- 12047037
TI  - Betaxolol inhibits extracellular signal-regulated kinase and P70S6 kinase
      activities and gene expressions of platelet-derived growth factor A-chain and
      transforming growth factor-beta1 in Dahl salt-sensitive hypertensive rats.
AB  - We evaluated the protective effects of long-term treatment with betaxolol, a
      specific beta-antagonist, on platelet-derived growth factor (PDGF) A-chain and
      transforming growth factor (TGF)-beta1 gene expression in the left ventricle of
      Dahl salt-sensitive hypertensive rats fed a high-salt diet. In addition, we
      evaluated the relations between these effects and coronary microvascular
      remodeling, expression of extracellular signal-regulated kinases (ERK) belonging
      to one subfamily of mitogen-activated protein kinases, and expression of p70S6
      kinase belonging to one subfamily of ribosomal S6 kinases. Betaxolol (0.9
      mg/kg/day, subdepressor dose) was administered for 5 weeks, from 6 weeks of age
      to the left ventricular hypertrophy stage at 11 weeks of age. Increased PDGF A
      chain and TGF-beta1 mRNA and protein expression were suppressed by betaxolol.
      Upregulated activities of ERK1/2 and p70S6 kinase phosphorylations were decreased
      by betaxolol. Betaxolol administration resulted in significant improvements in
      the wall-to-lumen ratio, perivascular fibrosis and myocardial fibrosis. Thus, we
      conclude that ERK1/2 and p70S6 kinase activities may play a key role in coronary
      microvascular remodeling of Dahl salt-sensitive hypertensive rats, and that
      beneficial effects of betaxolol on cardiovascular remodeling may be at least
      partially mediated by decreased PDGF A-chain and TGF-beta1 expression in the left
      ventricle.

PMID- 12047038
TI  - Ca2+ buffering function of the sarcoplasmic reticulum is increased in the carotid
      artery from spontaneously hypertensive rats.
AB  - To clarify whether the Ca2+ uptake function of the sarcoplasmic reticulum (SR)
      during arterial contraction is altered in hypertension, the effects of
      cyclopiazonic acid (CPA) and thapsigargin, which inhibit SR Ca2+-ATPase, on the
      contractile responses to Bay k 8644, an agonist of L-type Ca2+ channels, were
      compared in endothelium-denuded strips of carotid arteries from 13-week-old
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY).
      The addition of Bay k 8644 (1-300 nM) to the strips caused a concentration
      dependent contraction that was larger in SHR than in WKY. The contractile
      responses to Bay k 8644 were augmented by CPA (10 microM) or thapsigargin (100
      nM) in both strains. This augmentation was greater in SHR. Each of CPA and
      thapsigargin induced a relatively transient contraction, and both of these
      contractions were larger in SHR than in WKY. The basal 45Ca influx in this artery
      was larger in SHR than in WKY. The addition of caffeine (1-20 mM) caused a
      transient contraction that was larger in SHR than in WKY. Our results indicate
      that 1) the large Ca2+ influx during rest in the SHR carotid artery is strongly
      buffered by Ca2+ uptake into the superficial SR; and 2) the Ca2+ uptake function
      of the SR during the contraction with Bay k 8644 was increased in SHR compared
      with WKY. We conclude that the SHR carotid artery has an increased total capacity
      of SR for Ca2+ storage as an attempt to compensate for the large Ca2+ influx.

PMID- 12047039
TI  - Increased Ca2+ buffering function of sarcoplasmic reticulum in small mesenteric
      arteries from spontaneously hypertensive rats.
AB  - We compared the Ca2+ buffering function of the superficial sarcoplasmic reticulum
      (SR) during rest and during contraction in endothelium-denuded strips of small
      mesenteric arteries from 13-week-old spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto rats (WKY). The addition of caffeine (1-20 mM) caused a
      transient contraction in both strains, and the contraction was significantly
      larger in SHR. When the SR Ca2+ buffering function was eliminated by
      cyclopiazonic acid (CPA; 10 microM) or thapsigargin (100 nM), both of which
      inhibit SR Ca2+-ATPase, or by ryanodine (10 microM), which depletes the SR Ca2+,
      there was a larger contraction in SHR than in WKY, suggesting that the Ca2+
      buffering function of the SR during rest is more important in SHR than in WKY.
      Judging from the augmenting effects of these three agents on the contractile
      responses to Bay k 8644 (1-300 nM), an agonist of L-type Ca2+ channels, or
      norepinephrine (10(-9)-10(-4) M), an alpha-adrenoceptor agonist, the effects were
      significantly greater in SHR than in WKY. We conclude that 1) the Ca2+ influx
      during rest and during stimulation with Bay k 8644 or norepinephrine is strongly
      buffered by Ca2+ uptake into the superficial SR in the small mesenteric arteries
      from SHR and WKY; and 2) these Ca2+ buffering functions are increased in SHR
      because of the larger capacity of SR for Ca2+ storage.

PMID- 12047040
TI  - Contribution of endogenous vasopressin to regional hemodynamics in borderline
      hypertensive Hiroshima rats.
AB  - Inbred borderline-hypertensive Hiroshima rats (BHR) of the Wistar strain
      established in our laboratory are characterized by elevated plasma levels of
      vasopressin (Teranishi et al.: Jpn J Pharmacol 1999; 79: 251-255). To investigate
      the role of endogenous vasopressin in hypertension in BHR, we assessed the effect
      of a selective vasopressin V1 receptor antagonist (V1A) on regional hemodynamics
      using an electromagnetic flowmeter. The basal values of mean arterial pressure,
      heart rate, and regional resistances of renal and hindquarter vascular beds in
      conscious BHR were significantly higher than those in normotensive control rats
      (NCR). Injection of V1A (10 microg/kg) did not appreciably affect the
      hemodynamics in either animal. Successive administration of V1A after ganglionic
      blockade with hexamethonium bromide (C6; 25 mg/kg), however, significantly
      attenuated renal, mesenteric and hindquarter resistances in BHR but not in NCR.
      The hypotensive effect of V1A after sympathoinhibition was significantly greater
      in BHR than in both NCR and spontaneously hypertensive rats. However, the
      hypotensive effect induced by V1A was diminished only in BHR pretreated with a
      ganglionic blockade followed by injection of captopril (1 mg/kg). These findings
      indicate that BHR could be used as a new hypertensive model with an abnormality
      in endogenous vasopressin-mediated vasoconstriction appearing in the presence of
      angiotensin II after sympathoinhibition.

PMID- 12047041
TI  - Analyses of differential gene expression in genetic hypertensive rats by
      microarray.
AB  - We identified genes that were differentially expressed between spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) using cDNA microarray
      analysis, and analyzed the correlation between these genes and hypertension.
      Twenty four genes were found to be up-regulated and 20 were down-regulated in
      SHR. We selected 11 genes (6 up-regulated genes: SAH, Hsp70, MCT1, RBP, IDI1,
      Prion; and 5 down-regulated genes: Thrombin, Dyn, SOD3, Ela1, Gst Y(b)) and
      subjected them to an F2 cosegregation analysis. One hundred five F2 rats were
      obtained from the same strains used for microarray analysis, and blood pressure
      was measured directly with a catheter implanted in the femoral artery. The
      genotypes of monocarboxylate transporter 1 and glutathione S-transferase Y(b)
      subunit significantly affected diastolic blood pressure in F2 rats, and these two
      genes are located near each other on chromosome 2. However, quantitative trait
      loci (QTL) analysis in this region revealed that the QTL for diastolic blood
      pressure were from these two genes. Antihypertensive treatment with either
      enalapril or hydralazine only affected the expression level of Hsp70, which was
      up-regulated by hydralazine, probably through compensatory sympathetic
      activation. We were unable to associate the other 10 genes with hypertension in
      SHR. Based on these results, the identification of differentially expressed genes
      may not be an efficient method for selecting candidate genes for hypertension in
      the SHR-WKY system.

PMID- 12047042
TI  - Angiotensin II and IGF-I may interact to regulate tubulointerstitial cell
      kinetics and phenotypic changes in hypertensive rats.
AB  - Angiotensin II and insulin-like growth factor-I (IGF-I) are known to be actively
      involved in the pathogenesis of progressive renal injury, particularly in cell
      proliferation and phenotypic changes that contribute to tubulointerstitial
      injury. To investigate the possible mechanisms by which angiotensin II type 1
      receptor antagonist (AIIA) ameliorates renal injury in a renal ablation model and
      to determine the contribution of phenotypic changes and IGF-I to morphological
      changes, we examined 1) whether AIIA attenuated phenotypic changes as markers of
      alpha-smooth muscle actin (SMA) and vimentin, 2) whether AIIA altered renal IGF-I
      expression, and 3) the changes of tubulointerstitial cell kinetics between
      apoptosis (tested via terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      biotin nick end labeling, TUNEL) and cell proliferation (a test of proliferating
      cell nuclear antigen, PCNA). Following a sham operation (sham) or 5/6 nephrectomy
      (Nx), we administered E4177, a potent, selective competitive angiotensin II type
      1 receptor antagonist (AIIA), for 10 weeks. In Nx rats, SMA and vimentin
      expressions developed in injured tubulointerstitium, particularly in hypoperfused
      scar-adjacent areas, and there was an increase in renal IGF-I expressions. The
      TUNEL score increased 5-fold and PCNA increased 8-fold, compared with TUNEL and
      PCNA measurements in sham-operated rats. Renin expression in the juxtaglomerular
      apparatus was markedly suppressed in the Nx group, although de novo tubular renin
      expression appeared in Nx, compared with that in the sham group. E4177, both 10
      mg/kg (AIIA 10) and 1 mg/kg (AIIA 1), markedly ameliorated renal injury, although
      blood pressure was less affected in AIIA 1. Both AIIA 10 and AIIA 1 suppressed
      the neoexpressions of SMA and vimentin in an association with decreased IGF-I
      expression. Regarding cell kinetics, neither AIIA 10 nor AIIA 1 decreased the
      TUNEL score; rather, tended to increase, while PCNA was significantly suppressed
      by AIIA. In conclusion, one of the underlying protective mechanisms of AIIA in
      this model may be related to the modulations of angiotensin II-induced phenotypic
      changes and tubulointerstitial cell kinetics through IGF-I.

PMID- 12047043
TI  - Renoprotective effects of blockade of angiotensin II AT1 receptors in an animal
      model of type 2 diabetes.
AB  - To evaluate the efficacy of angiotensin II receptor blockers (ARBs) for use in
      the treatment of diabetic nephropathy, we examined the effects of olmesartan
      medoxomil (olmesartan), an angiotensin II type 1 (AT1) specific ARB, on the
      progression of nephropathy in Zucker diabetic fatty (ZDF) rats, an animal model
      of type 2 diabetes. We used 2 doses of olmesartan, a sub-antihypertensive dose
      and an antihypertensive dose, to specifically examine whether the drug exerts
      beneficial effects on the kidney without lowering blood pressure. Olmesartan
      mixed in the diet at a concentration of 0.001% (approximately 0.6 mg/kg/day) or
      0.01% (approximately 6 mg/kg/day) was administered for 19 weeks starting from 12
      weeks of age, when the animals developed microalbuminuria. Lean non-diabetic rats
      served as controls. ZDF rats had hyperglycemia, hyperinsulinemia, and moderate
      hypertension as compared to lean control rats. Plasma glucose and insulin
      concentrations were not affected by olmesartan, and blood pressure was lowered
      only by the high dose of olmesartan. Progressive proteinuria in ZDF rats was
      greatly (about 70%) suppressed by the high dose of olmesartan and moderately
      (about 30%) suppressed by the low dose that did not significantly lower blood
      pressure. ZDF rats exhibited hyperlipidemia and hypoalbuminemia, both of which
      were substantially corrected by treatment with olmesartan. The histological
      evidence of glomerular and tubular damage in the ZDF rats was also reduced by the
      drug. These results indicate that AT1 receptor blockade with olmesartan retards
      the progression of nephropathy associated with type 2 diabetes without affecting
      glucose metabolism, and that this renal protective effect is at least partly
      independent of the antihypertensive effect of the drug.

PMID- 12047044
TI  - Inhibition of migration and proliferation of rat vascular smooth muscle cells by
      a new HMG-CoA reductase inhibitor, pitavastatin.
AB  - The migration and proliferation of vascular smooth muscle cells (SMCs) are known
      to play roles in the pathogenesis of atherosclerosis. Therapy with a reductase
      inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) ("statin") produces
      significant alterations in various SMC functions. The objectives of the present
      study were to determine whether pitavastatin, a new chemically synthesized and
      powerful statin, can affect angiotensin II (Ang II)- and platelet-derived growth
      factor (PDGF)-induced migration and proliferation of cultured rat vascular SMCs.
      The effect of pitavastatin on cell viability was also examined in these cells.
      Migration was evaluated by the Boyden's chamber method using microchemotaxis
      chambers. As expected, Ang II and PDGF BB potently stimulated cell migration in a
      concentration-dependent manner. Pitavastatin significantly inhibited Ang II (10(
      6) mol/l)-induced migration at the concentrations of 10(-8) and 10(-7) mol/l.
      Pitavastatin also inhibited PDGF BB (1 ng/ml)-induced migration at concentrations
      between 10(-9) and 10(-8) mol/l in a relatively concentration-dependent manner.
      This statin modestly but significantly inhibited Ang II (10(-6) mol/l)- and PDGF
      BB (1 ng/ml)-induced DNA synthesis at concentrations between 10(-9) and 10(-7)
      mol/l. In addition, pitavastatin clearly inhibited Ang II (10(-6) mol/l)- and
      PDGF BB (1 ng/ml)-induced increases of cell number at concentrations between 10(
      9) and 10(-7) mol/l. Pitavastatin did not affect lactate dehydrogenase release
      from these cells at the concentrations used in this experiment. In a trypan blue
      exclusion test, dead cells stained with trypan blue were not found 24 h after
      treatment with 10(-9), 10(-8) or 10(-7) mol/l of pitavastatin. These findings
      suggest that pitavastatin suppresses the migration and proliferation stimulated
      by Ang II and PDGF BB without affecting cell viability. Pitavastatin may exert an
      anti-atherogenic effect, in part, through these mechanisms.

PMID- 12047045
TI  - Role of intrarenal angiotensin-converting enzyme in nephropathy of type II
      diabetic rats.
AB  - To examine the mechanism of nephropathy in Otsuka Long-Evans Tokushima Fatty
      (OLETF) rats, a recently developed type II diabetic model, we compared the long
      term effect of angiotensin-converting enzyme (ACE) inhibitor (imidapril, 1
      mg/kg/day), calcium channel blocker (amlodipine, 10 mg/kg/day), and insulin (5-10
      U/kg/day) on nephropathy of OLETF rats. Both imidapril and amlodipine, but not
      insulin, significantly reduced blood pressure of OLETF rats. Imidapril treatment
      significantly decreased urinary albumin excretions and improved
      glomerulosclerosis of OLETF rats, while amlodipine failed to improve nephropathy
      of OLETF rats despite lowering of blood pressure. Insulin treatment, which
      significantly decreased HbA1c throughout the treatment period, did not ameliorate
      nephropathy of OLETF rats. Serum ACE activity in OLETF rats was significantly
      lower than that in genetic control nondiabetic Long-Evans Tokushima Otsuka (LETO)
      rats. However, glomerular and aortic ACE activities in OLETF rats were
      significantly higher than those in LETO rats, and were significantly decreased by
      treatment with imidapril. Furthermore, immunohistochemical analysis of ACE in the
      kidney using specific antibodies indicated greater ACE immunostaining in the
      glomeruli and renal vessels of OLETF rats than in those of LETO rats. These
      observations demonstrate that ACE is involved in the development of nephropathy
      of OLETF rats and provide evidence that intrarenal ACE rather than circulating
      ACE may play an important role in nephropathy of this type II diabetic model.

PMID- 12047046
TI  - Enhancement of glomerular platelet-derived growth factor beta-receptor tyrosine
      phosphorylation in hypertensive rats and its inhibition by calcium channel
      blocker.
AB  - The molecular mechanism of glomerular injury in hypertension remains to be
      clarified. In this study, to examine the possible role of platelet-derived growth
      factor (PDGF) receptors in hypertensive glomerular injury, we specifically
      measured glomerular PDGF receptor tyrosine phosphorylation in various models of
      hypertensive rats using immunoprecipitation and Western blot analysis. A high
      salt diet significantly enhanced glomerular PDGF beta-receptor tyrosine
      phosphorylation of Dahl-salt sensitive rats (DS-rats) without an increase in its
      protein levels, and this enhancement was associated with an elevation of blood
      pressure and glomerular injury. Stroke-prone spontaneously hypertensive rats
      (SHRSP) at hypertensive phase also had higher glomerular PDGF beta-receptor
      tyrosine phosphorylation levels than control Wistar-Kyoto rats (WKY), while SHR
      did not. Thus, DS-rats and SHRSP, which are well known to represent severe
      glomerular injury, had the enhanced PDGF beta-receptor tyrosine phosphorylation,
      while SHR, a hypertensive model without significant glomerular injury had no
      increased tyrosine phosphorylation. Treatment of DS-rats or SHRSP with
      benidipine, a calcium channel blocker, significantly lessened the increase in
      glomerular PDGF beta-receptor tyrosine phosphorylation, reduction of urinary
      protein and albumin excretion. These results suggest that the enhanced activation
      of glomerular PDGF beta-receptors may be responsible for the development of
      hypertensive glomerular injury and that the suppression of this receptor
      activation by a calcium channel blocker may contribute to its renal protective
      effects.

PMID- 12047047
TI  - A novel cardioprotective agent, JTV-519, is abolished by nitric oxide synthase
      inhibitor on myocardial metabolism in ischemia-reperfused rabbit hearts.
AB  - We investigated the effect of a novel cardioprotective agent, JTV-519, with or
      without a nitric oxide synthase inhibitor, L-NAME, on the myocardial metabolism
      and contraction during ischemia and reperfusion by means of phosphorus 31-nuclear
      magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After 20 min
      normothermic global ischemia, postischemic reperfusion was carried out for 30
      min. JTV-519 was administered from 40 min prior to the global ischemia. Twenty
      one hearts were divided into three experimental groups consisting of 7 hearts
      each: a control group, a JTV-519 group perfused with JTV-519, and a JTV-519+L
      NAME group perfused with a combination of JTV-519 and L-NAME. During ischemia,
      the JTV-519 group showed a significant inhibition of the decrease in adenosine
      triphosphate (ATP) compared with both the control and JTV-519+L-NAME groups
      (p<0.01); the levels of ATP were 20+/-6, 56+/-9, and 40+/-4% in the control
      group, JTV-519 group, and JTV-519+L-NAME group, respectively. Both the JTV-519
      group and JTV-519+L-NAME group showed a significant inhibition of the increase in
      left ventricular end-diastolic pressure (LVEDP) compared with the control group
      (p<0.01). After postischemic reperfusion, the JTV-519 group again showed a
      significant improvement of ATP as compared with both the control and JTV-519+L
      NAME groups (p<0.01); the ATP levels were 52+/-4, 82+/-3, and 64+/-3% in the
      control group, JTV-519 group, and JTV-519+L-NAME group. In conclusion, JTV-519
      has a significant beneficial effect on myocardial energy metabolism during both
      ischemia and reperfusion. This beneficial effect was dependent on NO synthase.
      Furthermore, JTV-519 showed significant potential for improving myocardial
      relaxation during ischemia. This effect was not dependent on NO synthase.

PMID- 12047048
TI  - Antioxidant N-acetylcysteine inhibits vasoactive agents-potentiated mitogenic
      effect of mildly oxidized LDL on vascular smooth muscle cells.
AB  - Mildly oxidized LDL (mox-LDL) has been shown to induce monocyte-endothelial
      interactions and vascular smooth muscle cell (VSMC) proliferation, key events in
      the formation of the atherosclerotic lesion. Growth factors and vasoactive
      peptides are also thought to play a major role in atherogenesis. We examined the
      interaction between mox-LDL and well-known vasoactive agents such as serotonin (5
      HT), angiotensin II (Ang-II), endothelin-1 (ET-1), or urotensin II (U-II) in
      inducing DNA synthesis in VSMCs. Growth-arrested VSMCs were incubated with
      different concentrations of native LDL, mox-LDL, or highly oxidized LDL (ox-LDL)
      with 5-HT, Ang-II, ET-1, or U-II in the absence or presence of N-acetylcysteine
      (NAC), an intracellular free radical scavenger. DNA synthesis in VSMCs was
      examined by [3H]thymidine incorporation into cellular DNA. Mox-LDL and ox-LDL
      stimulated [3H]thymidine incorporation with a maximal effect at 5 microg/ml
      (211%, 154%), which values were significantly greater than that for native LDL
      (128%). 5-HT, Ang-II, ET-1, or U-II also stimulated [3H]thymidine incorporation
      in a dose-dependent manner. 5-HT had a maximal stimulatory effect at a
      concentration of 50 micromol/l (205%), Ang-II at 1.75 micromol/l (202%), ET-1 at
      0.1 micromol/l (205%), and U-II at 0.05 micromol/l (161%). When added together,
      mox-LDL (100 ng/ml)-induced [3H]thymidine incorporation was potentiated by low
      concentrations of 5-HT (1 micromol/l), Ang-II (0.5 micromol/l), ET-1 (1 nmol/l),
      or U-II (10 nmol/l) (114% to 330%, 325%, 338%, or 345%, respectively).
      Synergistic interactions of mox-LDL with 5-HT, Ang-II, ET-1, or U-II were
      significantly inhibited by NAC (400 micromol/l). Our results suggest that mild
      oxidation of LDL may enhance its atherogenic potential and exert a synergistic
      interaction with vasoactive agents in inducing DNA synthesis via the generation
      of reactive oxygen species in VSMCs.

PMID- 12047049
TI  - Is the word length effect in STM entirely attributable to output delay? Evidence
      from serial recognition.
AB  - Although it is generally accepted that the word length effect in short-term
      memory operates through output delay or interference, there is less agreement on
      whether it also influences performance through its impact on rehearsal. We
      investigated this issue by studying the effect of word length on recall and on a
      recognition task in which output delay was controlled. Word sequences were
      repeated exactly, or with one pair of words reversed. Two experiments using
      auditory presentation showed clear word length effects for both recall and serial
      recognition, although the magnitude of the effect tended to be less for
      recognition. A third experiment using visual presentation studied the effect of
      articulatory suppression during the recognition test; again we found a clear word
      length effect. It is concluded that the word length effect can influence
      retention through both rehearsal and output factors, as proposed by the
      phonological loop hypothesis.

PMID- 12047050
TI  - Inverting the modality effect in serial recall.
AB  - Differences in recall ability between immediate serial recall of auditorily and
      visually presented verbal material have traditionally been considered restricted
      to the end of to-be-recalled lists, the recency section of the serial position
      curve (e.g., Crowder & Morton, 1969). Later studies showed that--under certain
      circumstances--differences in recall between the two modalities can be observed
      across the whole of the list (Frankish, 1985). However in all these studies the
      advantage observed is for recall of material presented in the auditorily
      modality. Six separate conditions across four experiments demonstrate that a
      visual advantage can be obtained with serial recall if participants are required
      to recall the list in two distinct sections using serial recall. Judged on a list
      wide basis, the visual advantage is of equivalent size to the auditory advantage
      of the classical modality effect. The results demonstrate that differences in
      representation of auditory and visual verbal material in short-term memory
      persist beyond lexical and phonological categorization and are problematic for
      current theories of the modality effect.

PMID- 12047051
TI  - Grouping in short-term verbal memory: is position coded temporally?
AB  - The nature of the mechanisms that code item position in serial short-term verbal
      recall was investigated with reference to temporal grouping phenomena--effects
      that arise when additional pauses are inserted in a presented list to form groups
      of items. Several recent models attempt to explain these phenomena by assuming
      that positional information is retained by associating items with contextual
      information. According to two of the models--the Phonological Loop model (Hitch,
      Burgess, Towse, & Culpin, 1996) and the OSCAR model (Brown, Preece, & Hulme,
      2000)--contextual information depends critically on the timing of item
      presentation with reference to group onset. By contrast, according to the Start
      End model (Henson, 1998) and a development from it, which we label the Oscillator
      Revised Start-End model (Henson & Burgess, 1997), contextual information is
      independent of time from group onset. Three experiments examined whether coding
      of position is time dependent. The critical manipulation was to vary stimulus
      onset asynchrony from one group to the next in the same list. Lists of consonants
      were presented visually, but with vocalization in Experiment 1, auditorily in
      Experiment 2, and auditorily with articulatory suppression in Experiment 3. The
      pattern of order errors consistently favoured the predictions of the time
      independent models over those of the time-dependent models in that across-group
      transpositions reflected within-group serial position rather than time from group
      onset. Errors involving intrusions from previous lists also reflected within
      group serial position, thereby extending support for the time-independent models.

PMID- 12047052
TI  - Attention shifts and memory averaging.
AB  - When observers are asked to localize the final position of a moving stimulus,
      judgements may be influenced by additional elements that are presented in the
      visual scene. Typically, judgements arc biased toward a salient non-target
      element. It has been assumed that the non-target element acts as a landmark and
      attracts the remembered final target position. The present study investigated the
      effects of briefly flashed non-target elements on localization performance.
      Similar to landmark attraction, localization was biased toward these elements.
      However, an influence was only noted if the distractor was presented at the time
      of target disappearance or briefly thereafter. It is suggested that memory traces
      of distracting elements are only averaged with the final target position if they
      are highly activated at the time the target vanishes.

PMID- 12047053
TI  - Attentional cueing effect in the identification of words and pseudowords of
      different length.
AB  - Three experiments studied the influence of spatial attention on familiar and
      unfamiliar letter string identification. Sieroff and Posner's (1988) cueing
      procedure was used: A cue indicated in advance either the beginning (left) or the
      end (right) of a foveally presented letter string that participants were
      instructed to read aloud. Results showed that the precue had a stronger influence
      on pseudoword than on word identification. Similar results were obtained when
      participants were instructed to report the identity of the cue or not. For
      pseudowords, a cueing effect was obtained regardless of length (6, 8, and 10
      letters), whereas only 10-letter words showed such an effect, though to a lesser
      degree than pseudowords of the same length. However, results showed that shorter
      words were also influenced by the cue location when the exposure duration was
      reduced. Results are compatible with an early role of spatial attention in letter
      string processing, but they also suggest that the lexical status of a letter
      string can directly influence the distribution of attention before the
      identification process is completely achieved. Although orienting of spatial
      attention seems heavily involved in a pseudoword identification, some spatial
      attention mechanism could also take place in the case of familiar words. The
      results are discussed within two theoretical frameworks concerning the
      involvement of spatial attention in word identification: The "replacement" theory
      and the "redistribution" theory.

PMID- 12047054
TI  - Spoken language planning and the initiation of articulation.
AB  - Minimalist theories of spoken language planning hold that articulation starts
      when the first speech segment has been planned, whereas non-minimalist theories
      assume larger units (e.g., Levelt, Roelofs, & Meyer, 1999a). Three experiments
      are reported, which were designed to distinguish between these views using a new
      hybrid task that factorially manipulated preparation and auditory priming of
      spoken language production. Minimalist theories predict no effect from priming of
      non-initial segments when the initial segment of an utterance is already
      prepared; observing such a priming effect would support non-minimalist theories.
      In all three experiments, preparation and priming yielded main effects, and
      together their effects were additive. Preparation of initial segments does not
      eliminate priming effects for later segments. These results challenge the
      minimalist view. The findings are simulated by WEAVER++ (Roelofs, 1997b), which
      employs the phonological word as the lower limit for articulation initiation.

PMID- 12047055
TI  - The formation of structurally relevant units in artificial grammar learning.
AB  - A total of 78 adult participants were asked to read a sample of strings generated
      by a finite state grammar and, immediately after reading each string, to mark the
      natural segmentation positions with a slash bar. They repeated the same task
      after a phase of familiarization with the material, which consisted, depending on
      the group involved, of learning items by rote, performing a short-term matching
      task, or searching for the rules of the grammar. Participants formed the same
      number of cognitive units before and after the training phase, thus indicating
      that they did not tend to form increasingly large units. However, the number of
      different units reliably decreased, whatever the task that participants had
      performed during familiarization. This result indicates that segmentation was
      increasingly consistent with the structure of the grammar. A theoretical account
      of this phenomenon, based on ubiquitous principles of associative memory and
      learning, is proposed. This account is supported by the ability of a computer
      model implementing those principles, PARSER, to reproduce the observed pattern of
      results. The implications of this study for developmental theories aimed at
      accounting for how children become able to parse sensory input into physically
      and linguistically relevant units are discussed.

PMID- 12047056
TI  - Influences of metamemory on performance predictions for text.
AB  - When predicting future performance on tests over text material, do individuals
      estimate retention in addition to assessing comprehension? In Experiment 1,
      participants either rated their comprehension or predicted performance for each
      text, with lower ratings indicating lower confidence either in comprehension or
      in eventual performance. Judgement magnitude was significantly lower for
      performance predictions than for comprehension ratings, suggesting that
      predictions were based partly on retention estimates. In Experiment 2,
      predictions varied with anticipated test delay (15 min or 2 weeks) whereas
      comprehension ratings did not, providing further evidence that individuals
      estimate retention when predicting performance. Analyses of individual
      differences suggest that both good and poor performers incorporate retention
      estimates when predicting performance, but better performers do so in a more
      discriminative manner. Implications for theory of metacognitive judgements are
      discussed.

PMID- 12047057
TI  - Case-mixing effects on children's word recognition: lexical feedback and
      development.
AB  - Presenting words in MiXeD cAsE has previously been shown to disrupt naming
      performance of adult readers. This effect is greater on nonwords than it is on
      real words. There have been two main accounts of this interaction. First, case
      mixing may disrupt naming via non-lexical spelling-to-sound correspondences to a
      greater extent than it disrupts lexical naming. Alternatively, stored lexical
      knowledge of words may feed back to a visual analysis level during processing of
      a visually presented word, helping known words to overcome the visual disruption
      caused by case mixing. In the present study, when young children (aged 6 and 8
      years) were tested, case mixing did not disrupt nonword naming more than word
      naming. However, slightly older children (aged 9 years) demonstrated the same
      pattern of performance as adults. These results support the view that top-down
      lexical information can aid overcoming visual disruption to words, and that
      beginning readers have not developed the stored word knowledge necessary to allow
      this. In addition, a greater case-mixing effect on high-frequency words for the
      youngest age group (6-year-olds) suggests that their word recognition may be
      based more on wholistic visual features than is that of older children.

PMID- 12047058
TI  - Children's reading of words, pseudohomophones, and other nonwords.
AB  - In Experiment 1 children aged 8-9 and 9-10 years were tested for neighbourhood
      and pseudohomophone effects in nonword reading. Neighbourhood effects (N effects)
      were robust irrespective of group or type of nonword. Pseudohomophones were read
      more accurately than other nonwords but this finding was robust only for the
      younger 8-9-year-olds. High-frequency words were read more accurately than low
      frequency words, but the reverse applied to pseudohomophones based on high- and
      low-frequency words, although this was not robust. Error rates for the 9-10-year
      olds in Experiment 1 were low, and so it was difficult to interpret the lack of a
      pseudohomophone advantage for reading nonwords in this age group. Experiment 2
      was therefore carried out, which consisted of a replication of the first study
      with a further group of 9-10-year-olds, but pronunciation latencies were
      measured, as well as accuracy. All the effects obtained in Experiment 1 were
      replicated but, in addition, an advantage for pseudohomophones in terms of
      pronunciation latencies was observed. The implications for accounts of reading
      development are discussed.

PMID- 12047059
TI  - Responding to object files: automatic integration of spatial information revealed
      by stimulus-response compatibility effects.
AB  - Spatial information is assumed to play a central, organizing role in object
      perception and to be an important ingredient of object representations. Here,
      evidence is provided to show that automatically integrated spatial object
      information is also functional in guiding spatial action. In particular,
      retrieving nonspatial information about a previewed object facilitates responses
      that spatially correspond to this object. This is true whether the object is
      still in sight or has already disappeared. So, forming an object representation
      entails the integration and storage of action-related information concerning the
      action that the object affords.

PMID- 12047060
TI  - A Simon effect for stimulus-response duration.
AB  - A non-spatial variant of the Simon effect for the stimulus-response (S-R) feature
      of duration is reported. In Experiment 1 subjects were required to press a single
      response key either briefly or longer in response to the colour of a visual
      stimulus that varied in its presentation duration. Short keypresses were
      initiated faster with short than with long stimulus duration whereas the inverse
      was observed with long keypresses. In Experiment 2 subjects were required to
      press a left or right key (according to stimulus form) either briefly or longer
      (according to stimulus colour). The stimuli concurrently varied in their location
      (left or right) and duration (short or long), which were both task irrelevant.
      Approximately additive correspondence effects for S-R location and S-R duration
      were observed. To summarize, the results suggest that the irrelevant stimulus
      features of location and duration are processed automatically and prime
      corresponding responses in an independent manner.

PMID- 12047061
TI  - Motor learning by observation: evidence from a serial reaction time task.
AB  - This study sought evidence of observational motor learning, a type of learning in
      which observation of the skilled performance of another person not only
      facilitates motor skill acquisition but does so by contributing to the formation
      of effector-specific motor representations. Previous research has indicated that
      observation of skilled performance engages cognitive processes similar to those
      occurring during action execution or physical practice, but has not demonstrated
      that these include processes involved in effector-specific representation. In two
      experiments, observer subjects watched the experimenter performing a serial
      reaction time (SRT) task with a six-item unique sequence before sequence
      knowledge was assessed by response time and/or free generation measures. The
      results suggest that: (1) subjects can acquire sequence information by watching
      another person performing the task (Experiments 1-2); (2) observation results in
      as much sequence learning as task practice when learning is measured by reaction
      times (RTs) and more than task practice when sequence learning is measured by
      free generation performance (Experiment 2, Part 1); and (3) sequence knowledge
      acquired by model observation can be encoded motorically--that is, in an effector
      specific fashion (Experiment 2, Part 2).

PMID- 12047062
TI  - Attention to local form information can prevent access to semantic information.
AB  - Humphreys and Boucart (1997) have shown that when processing of local form is
      required for response, surrounding global information is automatically processed
      to a semantic level. The generality of this effect was investigated in two
      experiments in which the perceptual load of the relevant local form information
      was manipulated, as was uncertainty about perceptual load. Participants attended
      to a single line segment inside a picture of an animal or a vehicle and then
      decided which of two pictures in the target/distractor display that followed
      contained a line segment that matched the first in orientation. The perceptual
      load of the relevant local form information was either low (the matching line
      segment was one of the solitary line segments presented in the centre ofthe
      target and distractor pictures), or high (the matching line segment was part of
      one of the solitary letters presented in the centre of the target and distractor
      pictures). The semantic relations among the pictures were manipulated, and when
      perceptual load remained constant across trials, semantic relations affected
      performance in the low-load but not in the high-load condition. When perceptual
      load varied from trial to trial, there was no evidence of any semantic processing
      on either low- or high-load trials. The results suggest that in form-matching
      tasks, attentional priority can be given to local information, thus preventing
      access to semantic information derived from global shape. They further suggest
      that the distribution of attention is not dictated entirely by the actual
      perceptual demands of the relevant stimulus, indicating an important role for top
      down processing.

PMID- 12047063
TI  - Examining the activity-distribution model of visual attention with exogenous cues
      and targets.
AB  - LaBerge and his co-workers (e.g., LaBerge & Brown, 1986, 1989; LaBerge, Carlson,
      Williams, & Bunney, 1997) used an experimental method consisting of three rapid
      successive displays, each requiring a difficult letter discrimination, to show
      that visual attention is best accounted for with an activity-distribution model
      rather than a moving-spotlight model. The present study sought to further this
      line of investigation by inserting exogenous cues and targets, often used in
      studies that have found support for the moving-spotlight model, into the basic
      method used by LeBerge and colleagues. The results from three experiments were
      consistent with the activity-distribution model and not with the moving-spotlight
      model.

PMID- 12047064
TI  - Limits of rhythm perception.
AB  - To what extent are listeners sensitive to the time intervals separating non
      consecutive events in sound sequences? The subjects of Experiment 1 were
      presented with sequences of 20 identical tones in which the 10 odd-numbered tones
      or the 10 even-numbered tones made up an isochronous sub-sequence (with a
      periodicity of 0.5-1 s) whereas the other tones, acting as distractors, occurred
      at random moments. Such sequences appeared to be very difficult to discriminate
      from sequences without any timing regularity, which revealed a lack of perceptual
      sensitivity to their "second-order" intervals. Experiment 2 employed repetitive
      sequences in which the first-order intervals (separating consecutive tones) took
      two possible values, forming a ratio that subjects had to classify as larger or
      smaller than 2. The results of this experiment suggest that subjects were able to
      make use of second-order intervals in their task, but mainly due to the
      predictable nature of the sequences; the relative positions of subjective accents
      (Povel & Essens, 1985) had no significant effect on performance. It is concluded
      that the perception of subtle timing details in "ordinary" music may rest on
      nothing more than a sensitivity to the relations between first-order intervals
      (within a given auditory stream).

PMID- 12047065
TI  - Task-induced fatigue states and simulated driving performance.
AB  - States of fatigue are implicated in driver impairment and motor vehicle
      accidents. This article reports two studies investigating two possible mechanisms
      for performance impairment: (1) loss of attentional resources; and (2) active
      regulation of matching effort to task demands. The first hypothesis predicts that
      fatigue effects will be accentuated by high task demands, but the second
      hypothesis predicts that fatigue effects will be strongest in "underload"
      conditions. In two studies, drivers performed a stimulated driving task, in which
      task demands were manipulated by varying road curvature. In a "fatigue induction"
      condition, the early part of the drive was occupied by performance of a demanding
      secondary task concurrently with driving, after which the concurrent task ceased.
      Post-induction driving performance was compared with a control condition in which
      drivers were not exposed to the induction. In both studies, the fatigue induction
      elicited various subjective fatigue and stress symptoms, and also raised reported
      workload. Fatigue effects on vehicle control and signal detection were assessed
      during and after the fatigue induction. The fatigue induction increased heading
      error, reduced steering activity, and, in the second study, reduced perceptual
      sensitivity on a secondary detection task. These effects were confined to driving
      on straight rather than on curved road sections, consistent with the effort
      regulation hypothesis. The second study showed that fatigue effects were
      moderated by a motivational manipulation. Results are interpreted within a
      control model, such that task-induced fatigue may reduce awareness of performance
      impairment, rather than reluctance or inability to mobilize compensatory effort
      following detection of impairment.

PMID- 12047066
TI  - Chemical contaminants in juvenile gray whales (Eschrichtius robustus) from a
      subsistence harvest in Arctic feeding grounds.
AB  - Gray whales are coastal migratory baleen whales that are benthic feeders. Most of
      their feeding takes place in the northern Pacific Ocean with opportunistic
      feeding taking place during their migrations and residence on the breeding
      grounds. The concentrations of organochlorines and trace elements were determined
      in tissues and stomach contents of juvenile gray whales that were taken on their
      Arctic feeding grounds in the western Bering Sea during a Russian subsistence
      harvest. These concentrations were compared to previously published data for
      contaminants in gray whales that stranded along the west coast of the US during
      their northbound migration. Feeding in coastal waters during their migrations may
      present a risk of exposure to toxic chemicals in some regions. The mean
      concentration (standard error of the mean, SEM) of sigmaPCBs [1400 (130) ng/g,
      lipid weight] in the blubber of juvenile subsistence whales was significantly
      lower than the mean level [27,000 (11,000) ng/g, lipid weight] reported
      previously in juvenile gray whales that stranded in waters off the west coast of
      the US. Aluminum in stomach contents of the subsistence whales was high compared
      to other marine mammal species, which is consistent with the ingestion of
      sediment during feeding. Furthermore, the concentrations of potentially toxic
      chemicals in tissues were relatively low when compared to the concentrations in
      tissues of other marine mammals feeding at higher trophic levels. These chemical
      contaminant data for the subsistence gray whales substantially increase the
      information available for presumably healthy animals.

PMID- 12047067
TI  - Modeling the formation of PCDD/F in solid waste incinerators.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F) appear in
      unacceptable amounts in the gaseous emissions during the incineration of wastes
      containing significant quantities of chlorine and metals, such as MSW and medical
      waste. They are formed both in the gas phase at temperatures above 600 degrees C
      and on the surface of the solid phase (flyash) in the temperature range 400-225
      degrees C. Both the precursor (from existing smaller chlorinated molecules) and
      de novo (from elemental carbon) routes are involved. An empirically derived
      global model for their de novo formation on flyash in MSW and medical waste
      incinerators has now been extended to include the precursor mechanism, and a gas
      phase formation component, with separate rate expressions for PCDD and PCDF.
      Homogeneous PCDD formation is governed by the concentration of chlorophenols and
      PCDF by that of chlorophenols and chlorobenzenes. The result is more complete
      system which distinguishes between the gas and solid phase contributions to the I
      TEQ. An additional step for the adsorption of gaseous PCDD/F back onto the solid
      phase during cooling suggests this should be minimal in the gas ducts of an
      incinerator. The extended model has been tested against experimental data
      collected from a well-controlled pilot incinerator and commercial incinerators,
      and found to adequately describe the measured outputs. With the model it should
      be possible to predict the PCDD/F emissions from commercial incinerators,
      provided that the ash properties and the overall temperature-time profiles are
      known.

PMID- 12047069
TI  - Organochlorine contaminants in eggs: the influence of contaminated nest material.
AB  - Snake eggs were placed in a synthetic nest contaminated with known concentrations
      of six organochlorines (OCs) to evaluate whether OCs from contaminated nest
      material accumulate in eggs. It was hypothesized that contaminated nest material
      may have contributed to OC burdens in eggs observed previously. The six OCs
      tested included lindane, heptachlor, aldrin, dieldrin, endrin, and DDT. Eggs were
      removed at 0, 4, and 6 weeks and analyzed using gas chromatography with electron
      capture detection. Lindane was found at the highest concentration (153 ng/g at 4
      weeks and 162 ng/g at 6 weeks). The next highest uptake was for endrin (25 ng/g
      at 4 weeks and 106 ng/g at 6 weeks). Heptachlor, aldrin, and dieldrin were also
      taken up into the eggs, but DDT was not detected in any of the eggs at any
      sampling period. The concentration of OCs increased from week 4 to week 6 for all
      the OCs except DDT. Structure-activity relationships were examined to determine
      which physicochemical properties of the OCs tested could be used as predictors of
      uptake into the eggs. A variety of physicochemical properties were evaluated
      including vapor pressure and molecular connectivity (a numerical description of
      topology). Octanol-water partition coefficient (Kow) was a good predictor (r2 =
      0.63, p = 0.06) of OC uptake into the eggs using this limited data set.

PMID- 12047070
TI  - Comparison of PCDD/F and coplanar PCB concentrations in Japanese human adipose
      tissue collected in 1970-1971, 1994-1996 and 2000.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans
      (PCDFs) and coplanar biphenyls (Co-PCBs) were determined in Japanese human
      adipose tissues. Temporal trends were assessed by comparing data collected during
      1970-1971, 1994-1996 and 2000. Mean TEQ levels of PCDD/Fs in human adipose tissue
      showed a significant decrease from 31.6 +/- 9.2 pg-TEQ/g fat wt in 1970-1971 to
      11.9 +/- 7.4 pg-TEQ/g fat wt in 2000, and coplanar PCBs decreased from 35.4 +/-
      21.9 pg-TEQ/g fat wt in 1970-1971 to 15.3 +/- 8.2 pg-TEQ/g fat wt in 2000.
      However, some PCB congener concentrations did not change during this time. A
      comparison of data using the latest PCB-TEQ showed no significant changes.
      Therefore, research on source characterization and monitoring of short-term
      temporal trends on these compounds should be carried out continuously.

PMID- 12047068
TI  - PCDD/F and PCB history in dated sediments of a rural lake.
AB  - Concentrations of polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF)
      and biphenyls (PCB) were analysed from a sediment core, which had been sampled
      from a remote lake in Finland. The deepest subsamples were analysed from a depth
      of 4.0 m, and were more than 8000 years old. At the surface of the sediment core,
      low levels of industrial background contamination were detected. The sum of
      2,3,7,8-substituted PCDD/Fs was 35 ng/kg d.w. (dry weight), or 1.2 ng/kg d.w. in
      WHO's toxicity equivalent, WHO-TEQ. The annual accumulation rate of 2,3,7,8
      substituted PCDD/Fs was 1.26 ng m(-2) a(-1). Deeper in the core, PCDD/F
      concentrations ranged between 2.11 and 11.1 ng/kg d.w. (0.24 and 1.70 ng/kg d.w.
      WHO-TEQ) and the accumulation rate was 0.11 ng m(-2) a(-1). A characteristic
      PCDD/F congener profile was found in all pre-industrial sediment layers. The
      order of concentrations was OCDD > 1,2,3,4,6,7,8-HpCDD > 1,2,3,7,8,9-HxCDD >
      1,2,3,4,7,8-HxCDD > 2,3,7,8-TCDD, and concentrations of 2,3,7,8-chlorinated
      dibenzofurans were below the detection limit. Similar congener profiles have
      previously been described in samples for which natural PCDD/F formation has been
      proposed. PCBs were present at low levels in all of the sediment samples. The sum
      of the PCB concentrations of the sediment subsamples ranged between 50 and 2540
      ng/kg d.w., and the three predominant congeners in the core were PCBs 18, 52, and
      110.

PMID- 12047071
TI  - Effect of dissolved humic matters on the leachability of PCDD/F from fly ash-
      laboratory experiment using Aldrich humic acid.
AB  - The effect of dissolved humic matters (DHM) on the leachability of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F) in
      fly ash was studied theoretically and in laboratorial condition to verify the
      previous results for pilot and field experiment of incineration residues
      landfill. In theoretical review, it was shown that DHM could influence the actual
      solubility and leachability of PCDD/F. The higher concentration of DHM showed the
      higher leachability of PCDD/F. In the leaching test, three different DHM
      concentrations and pHs of solutions were adopted to fly ash samples imaging the
      various characteristics of municipal solid waste leachate. It was proved
      experimentally that the leachability of PCDD/F increased with increasing DHM
      concentration in all pH conditions. The highest leachability was shown at the
      highest pH. Isomer distribution patterns of PCDD/F in all leachates were similar
      in all pH conditions. It backed up the distribution theory of PCDD/F between DHM
      and water.

PMID- 12047072
TI  - On-fibre photodegradation studies of polychlorinated biphenyls using SPME-GC-MS
      MS: a new approach.
AB  - The known advantages of solid-phase microextraction as a simple, one-step, rapid
      and solvent free extraction technique are exploited to study the photodegradation
      kinetics of polychlorinated biphenyls "on-fibre". The obtained results show the
      possibilities of this new approach not only to monitor the photolysis pathways of
      such compounds but to determine the photoproducts produced at different
      irradiation times and/or wavelengths. Photoproducts of PCB decomposition were
      less chlorinated biphenyls, among them some coplanar congeners have been found,
      which is important from a toxicological point of view.

PMID- 12047073
TI  - Selecting chemical substances for the UN-ECE POP protocol.
AB  - In 1998 the UN-ECE POP Protocol was signed. Sixteen substances are included in
      the protocol. They can be characterised as persistent, bioaccumulating and toxic
      organic substances prone to long-range atmospheric transport. The Dutch Ministry
      of Housing, Physical Planning and the Environment started a project to select
      possible candidates for the protocol. In the first phase of the project possible
      candidates were selected using the so-called 'PTB-database' applying the criteria
      from the protocol. From the 12 substances that met the criteria four substances
      were selected for which preliminary risk profiles were drafted: polychlorinated
      naphthalenes, dicofol, hexachlorobutadiene and pentachlorobenzene. These profiles
      are presented. Revised profiles have to be prepared for the UN-ECE LRTAP Ad hoc
      Expert Group on persistent organic pollutants (POPs). Ultimately, the process
      should lead to a proposal to include additional POPs to the UN-ECE POP Protocol.

PMID- 12047074
TI  - Polybrominated diphenyl ethers (PBDEs) in marine fish and blue mussels from
      southern Greenland.
AB  - Levels of polybrominated diphenyl ethers (PBDEs) have not previously been
      reported in Greenland. In this study shorthorn sculpins (Myoxocephalus scorpius)
      were sampled at three locations in southern Greenland; Usuk (no population),
      Igaliko (population 40) and Qaqortoq (population 3200). Furthermore uvak (Gadus
      ogac), spotted wolffish (Anarhichas minor), starry ray (Raja radiata), and blue
      mussels (Mytilus edulis) were collected at Usuk. Pooled samples of fish liver and
      blue mussel were analysed for lower brominated PBDEs (BDE-47, BDE-99, BDE-100 and
      BDE-153). The highest PBDE levels were found in Qaqortoq followed by Igaliko and
      Usuk. The measured sum PBDE concentrations in shorthorn sculpin collected at
      Qaqortoq, Igaliko and Usuk, were 8.2, 3.1 and 2.1 all in units of microg kg(-1)
      wet weight. In female and male uvak collected at Usuk PBDE levels of 7.1 and 12.0
      microg kg(-1) wet weight were measured, while the concentrations were 1.2 microg
      kg(-1) in spotted wolffish, 1.4 microg kg(-1) in starry ray and 0.11 microg kg(
      1) in blue mussels from the same locality all measured on a wet weight basis. The
      highest concentrations were measured in uvak, a top-predator on fish indicating
      that PBDEs are biomagnifying. The level of tetra-hexa BDEs is 15-24 times lower
      than PCB levels measured in the same samples, except for shorthorn sculpin
      collected at Qaqortoq, where the level of PBDEs was 40 times lower than the level
      of PCBs. The high concentration of PCBs relative to PBDEs in shorthorn sculpin
      collected at Qaqortoq signifies a local emission of PCBs, which is higher than
      the local emission of PBDEs.

PMID- 12047075
TI  - Tracking chlordane compositional and chiral profiles in soil and vegetation.
AB  - The cycling of chlordane and other persistent organic pollutants through the
      environment must be comprehensively elucidated to assess adequately the human
      health risks posed from such contaminants. In this study the compositional and
      chiral profiles of weathered chlordane residues in the soil and vegetative
      compartments were investigated in order to provide details of the fate and
      transport of this persistent pesticide. Zucchini was planted in a greenhouse in
      three bays containing chlordane-contaminated soil. At harvest the vegetation and
      soil were extracted and analyzed for chlordane content using chiral gas
      chromatography/ion trap mass spectrometry. Both achiral and chiral chlordane
      components were quantified. The chlordane concentration in the rhizosphere (soil
      attached to roots) was significantly less than that in the bulk soil. However,
      the enantiomeric ratio of the chiral components and overall component ratios had
      changed little in the rhizosphere relative to the bulk soil. Significant levels
      of chlordane were detected in the vegetation, the amount varying in different
      plant tissues from a maximum in roots to a minimum in fruit. In addition to the
      chlordane concentration gradient in plant tissues, significant shifts in
      compositional profile, as indicated by the component ratios, and in chiral
      profile, as indicated by the enantiomeric ratio, of the contaminant were observed
      in the plant tissues. The data indicate that abiotic processes dominate the
      transport of the chlordane components through the soil to the plant. This is the
      first report of the effect of rapid biotic processes within the plant compartment
      on chlordane compositional and chiral profiles.

PMID- 12047076
TI  - A study of polychlorinated dibenzo-p-dioxins and dibenzofurans in the atmosphere
      of Hong Kong.
AB  - A total of 27 ambient air samples of were collected from six locations in Hong
      kong during the period of January-August, 2000 and analysed for polychlorinated
      dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). In all sampling locations,
      higher concentrations of PCDDs/PCDFs, ranging from 0.03 to 0.43 pg I-TEQ/m3 were
      measured in winter months (January and March) than in the summer months (July and
      August) of concentrations at 0.018-0.025 pg I-TEQ/m3. These concentrations are
      similar to annual ranges reported earlier for two Hong Kong urban sites and other
      urban cities in Asia. Europe, and the United States. Despite significant seasonal
      variations in ambient air concentrations of PCDD/Fs (expressed in I-TEQ) were
      observed, the congener profiles of all the samples in this study period were
      similar, with OCDD, 1,2,3,4,6,7,8-HpCDD, OCDF and 1,2,3,4,6,7,8-HpCDF being the
      predominant species. However, the homologue profiles for the samples collected at
      the six locations of this study were found to display significantly different
      spatial and seasonal trends.

PMID- 12047077
TI  - Environmental risk assessment of phosphonates, used in domestic laundry and
      cleaning agents in The Netherlands.
AB  - In the long-term cooperative project Voluntary Plan of Action (1990) between the
      Dutch Soap and Detergent Association (NVZ) and the Dutch Ministry of Housing,
      Spatial Planning and the Environment (VROM) environmental risk assessments of
      several main components of laundry cleaning formulations were completed. As a
      part of that project the environmental risk assessment of HEDP, ATMP, EDTMP and
      DTPMP phosphonates used in detergent applications has been carried out according
      to the EU Technical Guidance Document for Environmental Risk Assessment for New
      and Existing Chemicals. All PEC/PNEC ratios were well below 1. Results of this
      assessment based on the total industry volumes from 1995 and 1998 indicate that
      the environmental risk of these phosphonates is low in The Netherlands with
      properly functioning sewage treatment plants.

PMID- 12047078
TI  - Effects of restricted feeding on physiological stress parameters in growing
      broiler breeders.
AB  - 1. In previous studies, a lack of agreement in measurements of plasma
      corticosterone concentrations and heterophil:lymphocyte (H/L) ratio as
      physiological indices of stress, caused by hunger and frustration in restricted
      fed broiler breeders, was observed. It could be suggested that the differences
      between previous studies were caused by differences in duration of restriction
      and time of the day of the measurements. Therefore, in the present study the
      plasma corticosterone concentration and the H/L ratio were again determined in
      restricted- and ad libitum-fed growing broiler breeders, taking possible causes
      of disagreement between previous studies into account. In addition, we measured
      the daily rhythm in body temperature and heart rate, and the corticosterone
      responses to an acute stressor as physiological indices of stress. 2. Female
      broiler breeders (64 per treatment, housed in groups of 4 birds) were used in the
      experiment. Behaviour, baseline plasma corticosterone concentrations and H/L
      ratio were determined at 21 d of age (immediately after the start of food
      restriction), and at 42 and 63 d of age. Body temperature, heart rate and
      activity were measured by radiotelemetry for 36 h at 49 and 70 d of age. In
      addition, the plasma corticosterone response to acute stress (5 min manual
      restraint) was measured at 77 or 78 d of age. 3. Restricted broiler breeders had
      higher plasma corticosterone concentrations at 42 and 63 d of age, but no
      differences in H/L. ratio were found between restricted birds and unrestricted
      control birds. Restricted broiler breeders had a higher corticosterone response
      to 5 min manual restraint than unrestricted birds. Restricted birds displayed a
      clear day-night rhythm in body temperature, heart rate and activity whereas such
      a rhythm was blunted in ad libitum-fed birds. 4. It is discussed that some
      physiological differences (plasma corticosterone concentrations, body temperature
      and heart rate) between ad libitum-fed and restricted broiler breeders may have
      been caused by differences in metabolic rate as well as by differences in the
      level of stress. It is concluded that a combination of behavioural measurements
      and a wide range of physiological parameters should be used for the assessment of
      stress in growing broiler breeders.

PMID- 12047079
TI  - Behaviour of laying hens in two types of aviary systems on 25 commercial farms in
      Sweden.
AB  - 1. Fifty-one flocks of laying hens in two high-density loose-housing systems were
      studied on 25 commercial farms in Sweden as part of a government test programme
      for evaluating new systems for laying hens. Six different hybrids were used in
      group sizes ranging from 250 to 5 000 birds. Stocking-densities varied from 10.2
      to 19.1 birds per m2 floor area. No birds were beak trimmed. 2. The distribution
      of birds in the system, the frequency and location of aggressive pecks and
      feather pecks, the dust bathing activity and the birds' fear reaction to the
      keeper and to a novel object were measured. Direct behaviour observations were
      carried out twice per flock, at weeks 35 and 55. 3. The proportion of birds at
      the different locations was relatively constant across the 8-h observation period
      in the tiered system, but changed over time in the perch system, which may
      reflect a difference in access to resources between the systems. At night the top
      perches/tiers were preferred although when stocking-density increased, other
      sites were also used. 4. Aggression occurred mainly on the litter or in the nest
      areas. It did not differ between hybrids, but increased with age in the tiered
      system. Feather pecks occurred mainly on the litter. Brown hybrids feather pecked
      more than white ones, while white hybrids reacted more both to the keeper and to
      a novel object than did the brown hybrids. 5. It was concluded that access to
      nests was insufficient in both systems, as was litter space. Feed space was
      insufficient in the tiered system if food requirements increased. Design of the
      top perches, in the perch system, should be improved to allow birds to perch high
      up in the system without blocking access to feed etc. for others.

PMID- 12047080
TI  - Ontogeny of behaviour in intact and beak trimmed layer pullets, with special
      reference to preening.
AB  - 1. The effects of commercial beak trimming on layer pullet behaviour were
      investigated, with special reference to preening. 2. One-d-old chicks, 96 in all,
      were housed in 12 litter floor pens, with 8 birds in each, to 20 weeks of age.
      Approximately one quarter of the beak was trimmed in all birds in half of the
      pens (BT) at 8 d of age using a hot blade debeaker. The birds in the other pens
      remained intact (NBT). 3. There was no significant effect of beak trimming on
      body weight at any age. At the end of the study, upper mandible lengths were
      shorter in BT birds. 4. Beak trimming had very little effect on behaviour. NBT
      birds showed more litter-directed behaviour than did BT birds, and BT birds spent
      more time in preening directed at the preen gland, and at the back while sitting.
      5. Feather damage was minimal and there was no difference in mean feather damage
      scores between treatments at any age. 6. The young age and small amount of beak
      removed during beak trimming may be at least partly responsible for the lack of
      effects of beak treatment on behaviour and plumage condition.

PMID- 12047081
TI  - Preference and motivation of laying hens to eat under different illuminances and
      the effect of illuminance on eating behaviour.
AB  - 1. In experiment 1, 10 laying hens were given the choice to eat food pellets from
      any of 4 food bowls illuminated by overhead, incandescent luminaires at <1, 6, 20
      or 200 lux. During a trial hens were allowed to eat for 5 min. After each minute
      had elapsed (from the start of eating) the light sources were extinguished and
      the illuminances re-assigned to the food bowls in a random manner. Each hen
      received two trials, one where the food was freely available and another where it
      was hidden in a sand and gravel mix. 2. The hens chose to eat for most time in
      the brightest (200 lux) and least in the dimmest (<1 lux) environments for both
      free and hidden food (free: 5.9, 10.5, 10.4, 15.7s for increasing illuminance;
      Hidden: 5.5, 9.8, 9.1 and 15.7s. 3. In experiment 2, 9 hens were trained to peck
      at either an illuminated or unilluminated panel to access a food reward behind a
      guillotine door for 3 s. Five hens were trained to peck the illuminated panel to
      access food brightly lit (200 lux) or the unilluminated panel to access food
      dimly lit (<1 lux); 4 hens were trained vice versa. The flock was then divided
      into three groups of three, and three treatments imposed on each group in a Latin
      square arrangement. In treatment 1, one peck at either panel allowed access to
      the chosen light environment (F1:F1). In treatment 2, 5 pecks were required to
      access food brightly lit on a variable ratio, but only one to access food dimly
      lit (ratio V5:F1). In treatment 3, the variable ratio was increased to V10:F1 to
      access food in the light. 4. Over 40 trials for each hen, the mean number of
      attempts to eat food in the light (where the panel which allowed access to food
      brightly lit was pecked at least once) was 34.5 for F1:F1, 12.1 for V5:F1 and 8.5
      for V10:F1. The mean number of food rewards taken in bright light was 34.5, 3.1
      and 1.8, respectively. For both variables, the difference between F1:F1 and V5:F1
      was significant but not between V5:F1 and V10:F1. By interpolation of the
      'attempts' data, it was estimated that hens would work 2.3 times harder to gain
      access to food brightly lit than for food dimly lit. 5. In experiment 3, the
      influence of the same illuminances applied over a food bowl as in experiment 1
      (<1, 6, 20 or 200 lux) on the number of pecks/min, food consumed/min, food
      consumed/peck and the force of pecks was examined. 6. The amount of food consumed
      was lowest in the dimmest environment (3.1 vs 7.5, 7.4 and 7.1 g/ min for
      increasing illuminance, respectively); as was the number of pecks (35.6 vs.
      125.0, 123.1, and 125.4 pecks/min respectively for increasing illuminance). The
      amount consumed per peck did not vary significantly with illuminance. The mean
      peck force showed a trend to be lowest in the dimmest environment (5.3 vs. 6.6,
      7.0 and 6.6 N respectively, for increasing illuminance). 7. Overall, the hens
      showed a preference and appeared motivated to eat in bright as opposed to dim
      light. The hens were unwilling to eat at low illuminances although the
      'efficiency' of eating (g/peck) was not impaired significantly. These data may
      have implications for novel lighting systems and those where hens are required to
      eat in the dark or in very dim light.

PMID- 12047083
TI  - Detection of early embryonic development in chicken eggs using visible light
      transmission.
AB  - 1. In two separate experiments, the possibility of detecting embryonic
      development in chicken eggs was assessed using the same spectrophotometric method
      used to detect blood in Table eggs, using a combination of two wavelengths (577
      and 610 nm) of the transmission spectrum. 2. In the first experiment, during the
      first 10 d of incubation, transmission spectra of 30 Hisex White eggs and 30
      Hybro eggs were measured daily. 3. In the second experiment, 292 Hisex White eggs
      were incubated. Seven groups were randomly assigned. Six received an injection of
      sodium azide (NaN3) at different times during incubation in order to stop
      embryonic development, and during the first 12 d of incubation the transmission
      spectrum was measured daily. The acoustic resonance analysis method was also used
      on a group of uninjected eggs. 4. In the first experiment, it was possible to
      detect embryonic development from 120 h of incubation onwards in fertile eggs. In
      the second experiment changes in light transmission due to embryonic development
      were detected from 108 h of incubation. Detection of embryonic development using
      the acoustic resonance analysis method in the second experiment was possible only
      from 120 h of incubation. 5. It was concluded that the detection of embryonic
      development using visible light transmission is not directly linked with the
      formation of blood, but with the formation of sub-embryonic fluid, which takes
      place from 72 h of incubation onwards. This fluid makes the yolk sac translucent
      so that absorption of light at 577 nm can be detected.

PMID- 12047082
TI  - Ontogeny of 5-aminolevulinic dehydratase and porphobilinogen deaminase activities
      in the yolk sac membrane and liver of chick embryos.
AB  - 1. Chick embryos of 7, 9, 11, 12, 13, 14, 15, 17 and 19 d of embryonic
      development were examined to determine the activities of 5-aminolevulinic
      dehydratase (ALA-D, EC 4.2.1.24) and porphobilinogen deaminase (PBG-D, EC
      4.3.1.8). 2. Liver and yolk sac membrane ALA-D specific activities showed a
      maximum between 12 and 13 d of embryonic development, yolk sac membrane PBG-ase
      activity a maximum at 9 d and at 7 d in liver. Total activities of ALA-D and PBG
      D were not constant during the course of embryonic development but probably
      related to the changes of intensity of haem synthesis. 3. ALA-D and PBG-ase
      activities were higher in yolk sac membrane than in liver, showing the importance
      of the yolk sac membrane as erythropoietic tissue. PBG-D catalysed the rate
      limiting reaction of the cytosolic steps in the biosynthetic pathway in both
      tissues.

PMID- 12047085
TI  - Manufacture of spent hen ayami and its utilisation in meatloaf and fresh sausage.
AB  - 1. Spent hens were slaughtered, hand deboned and then further processed into a
      surimi-like material, ayami, which was used to manufacture meatloaf and fresh
      sausage as value-added products. 2. Yields of deboned muscle and of ayami (% of
      deboned muscle) were 34.4 to 43.7% and 63.6%, respectively. 3. The ayami
      composition was: moisture 78.3%, ash 0.28%, fat 3.7%, protein 15.3% and
      carbohydrate 2.4%. Its pH value ranged from 5.65 to 6.10, and the water-holding
      capacity from 35.6 to 37.8. 4. Three formulations of meatloaf were prepared with
      0, 7.5 and 15% chicken fat and with a blend of herbs and spices. The most
      acceptable of the three was used for the manufacture of meatloaf and fresh
      sausage. 5. Microbial testing was conducted on freshly prepared formulation of
      the meatloaf (15% fat) and sausage, and on frozen stored samples (-18 degrees C,
      10 d). All had acceptable microbial quality. 6. Sensory analysis showed that the
      15% fat formulation of the meatloaf was the most liked and the fresh sausage was
      consumer acceptable.

PMID- 12047084
TI  - Evaluation of an early granulocytic response of chick embryos inoculated with
      herpesvirus of turkeys.
AB  - 1. Early granulocytic response was evaluated in chick embryos inoculated with
      herpesvirus of turkeys (HVT). 2. Fifty 10-d-old specific pathogen-free embryos
      were divided into two groups, inoculated via yolk sac. Group 1 were inoculated
      with a complete dose of HVT and group 2 with vaccinediluent only. 3. Samples were
      taken for histological evaluation of yolk sac, liver, chorioallantoic membrane,
      brain and heart from 5 embryos per group on days 12, 14, 16, 18 and 20 of
      embryonic life. 4. Increases in numbers of granulocytes were detected on days 14
      and 16 in the yolk sac, and on d 14 and 20 in the liver of in embryos, which
      received HVT. In addition, the chorioallantoic membrane was infiltrated with
      granulocytes. 5. The results confirm that granulopoiesis in the yolk sac is
      stimulated in the early stages of incubation if a viral antigen is present. The
      virus also appears to trigger the presence of granulocytes in embryonic liver and
      chorioallantoic membranes.

PMID- 12047087
TI  - Effect of frequency of the stunning current waveform on carcase and meat quality
      of turkeys processed in a commercial plant in the UK.
AB  - 1. This study compared the effects of electrical stunning delivered using high
      and low frequency waveforms on carcase and meat quality of turkeys processed
      under commercial conditions. 2. The use of a high frequency waveform (1400 Hz)
      resulted in a faster bleedout and an improvement in carcase quality associated
      with a substantial reduction in haemorrhagic downgrading conditions. 3. Frequency
      of the applied waveform influenced breast muscle pH and colour although the
      magnitude of the differences was considered to be of minimal significance in
      influencing consumer perception.

PMID- 12047086
TI  - Effect of dietary oregano essential oil on performance of chickens and on iron
      induced lipid oxidation of breast, thigh and abdominal fat tissues.
AB  - 1. We studied the effect of dietary oregano essential oil (50 and 100 mg/kg of
      feed) on the performance of broilers, and determined the susceptibility of the
      resulting broiler meat to iron-induced lipid oxidation. 2. Performance of the
      birds was unaffected by the experimental diets. Therefore, dietary oregano oil
      exerted no growth-promoting effect on broilers. 3. Iron-induced lipid oxidation
      showed that as oregano oil increased in the diet, malondialdehyde values
      decreased in tissue samples, suggesting that the oil, particularly at 100 mg/kg
      of feed, exerted an antioxidant effect on chicken tissues. 4. Dietary alpha
      tocopheryl acetate supplementation at 200 mg/kg of feed displayed greater
      antioxidant activity than oregano oil at either supplementation rate. 5. Thigh
      muscle was more susceptible to oxidation than breast muscle, although the former
      contained alpha-tocopherol at higher concentration. Muscle alpha-tocopherol is an
      important factor influencing lipid oxidation, but the influence of
      polyunsaturated fatty acids and content of pro-oxidants must be taken into
      consideration too.

PMID- 12047088
TI  - Measuring the eggshell strength of 6 different genetic strains of laying hens:
      techniques and comparisons.
AB  - 1. Eggshell quality was compared in 6 different strains of laying hens. Three
      strains were commercial; the three others were experimental. 2. Four different
      variables describing the strength of eggshells were investigated. Three of them
      were the classical ones eggshell thickness, shell stiffness measured during quasi
      static compression and breaking force. Dynamic stiffness, introduced by Coucke
      (Ph.D. Thesis, KU Leuven, 1998), was the 4th. The fact that this measurement is
      dynamic could be helpful in genetic selection for eggshell breakage, because
      forces applied to the egg in practice are dynamic, rather than static. 3. Hisex
      White hens produce eggs with the strongest eggshell, in terms of all 4 eggshell
      variables. However, their shell quality in terms of breaking force did not remain
      constant over the laying period, unlike 4 other strains. 4. All strains showed a
      decline in quasi-static stiffness over time. 5. The eggshell thickness of three
      strains showed a decline over time. 6. Dynamic stiffness remained constant or
      improved in all strain. 7. All variables describing the mechanical eggshell
      strength gave different information.

PMID- 12047089
TI  - Effects of the rate of muscle post mortem pH fall on the technological quality of
      turkey meat.
AB  - 1. This experiment evaluated the influence of the rate of post mortem pH fall on
      the processing ability of turkey meat. 2. Four hundred and twenty male turkeys
      from a selected pure line (grand-parental female line, BUT Ltd) were slaughtered
      at 16 weeks of age in a commercial plant and pH was measured in the Pectoralis
      superficialis (PS) and Ilio tibialis (IT) muscles, at 20 min post mortem. Three
      groups of PS muscle differing in pH20 and two groups of IT muscle differing in
      pH20 were constituted and processed as cured-cooked white meat and turkey ham,
      respectively. 3. The technological yield was lower in the groups showing the
      lowest pH20 (97.4% at pH20 5.90 vs 98.6 and 98.3% at pH20 6.24 and 6.55,
      respectively, for white meat and 97.2% (pH20 6.28) vs 98.3% (pH20 6.56) for
      turkey hams). The groups showing the lowest pH20 also showed higher drip loss in
      commercially packed products. 4. Acceptability tests of processed products were
      carried out in the commercial plant. Texture and taste of white meat were better
      in the highest pH group but the overall impression was similar in the lowest and
      the highest pH groups (mean scores of 4.2 and 4.1, respectively), due to better
      colour in the former (mean scores of 4.4 for the lowest pH20 group vs 4.0 and 3.9
      for the medium and highest pH20 groups, respectively). 5. For turkey hams, the
      meat processed from the highest pH group got the best score for all items.

PMID- 12047090
TI  - Effects of wheat variety and specific weight on dietary apparent metabolisable
      energy concentration and performance of broiler chicks.
AB  - 1. This study used 4 wheat cultivars (Brigadier, Chaucer, Consort, Reaper) from
      three locations (Crossnacreevy, C; Downpatrick, D; Limavady, L), which had given
      rise to differences in wheat specific weight (SW), to examine the relationships
      between apparent metabolisable energy (AME) concentration, broiler performance
      and wheat SW. 2. The diets contained (g/kg): wheat 744, casein 142, blended
      vegetable fat 50, dicalcium phosphate 22, potassium bicarbonate 10.8, sodium
      bicarbonate 7.5, arginine 5, methionine 2, binder 8, trace minerals/vitamins 7.2,
      titanium dioxide 1.5. The diets were heat-treated (80 degrees C for 2 min) prior
      to pelleting (3 mm die). 3. SW ranged from 63 to 77 kg/hectolitre (hl), averaging
      66, 69 and 76 kg/hl at D, C and L, respectively. In vitro viscosity of the wheat
      samples ranged from 5.2 to 17.5 cps and thousand grain weight (TGW) from 33.4 to
      47.3 g. Mean TGW was similar at C and D (38.7, 37.0 g) but higher at L (43.1 g).
      In vitro viscosity was similar at C and L (11.2, 10.2 cps) but somewhat higher at
      D (14.4 cps). Crude protein (6.25 N) ranged from 116 to 147 g/kg and tended to be
      higher at D. Starch, which ranged from 612 to 656 g/kg, was least at D (617 g/kg)
      and greatest at L (641 g/kg). 4. Crude protein, crude fibre and total non-starch
      polysaccharide (NSP) were negatively correlated with SW, the R2 being
      respectively 0.38 (P<0.05), 0.16 (NS) and 0.45 (P<0.05). TGW and starch
      concentration were positively correlated with SW (R2=0.70, 0.44, respectively).
      There was a weak (NS) negative relationship (R2=0.19) between in vitro viscosity
      and SW. For both TGW and in vitro viscosity, correlations improved when variety
      was taken into account (R2=0.95, 0.92, respectively). 5. There were no
      significant effects of variety on dry matter (DM) intake or live weight gain
      (LWG). Gain: food was significantly higher (P<0.05) for Consort than for the
      other three varieties and the metabolisable energy ratio (ME:GE) just failed to
      attain significance (P=0.062). Calculated wheat AME (MJ/kg DM) was significantly
      (P<0.05) higher for Consort than for the other three wheats. There was a good
      correlation (R2=0.49) for the total data set between gain:food and ME:GE. In vivo
      viscosity varied from 13.6 to 28.6 cps for individual treatments and was
      significantly affected by variety (P<0001). 6. Although there were no significant
      differences in DM intake or LWG due to site the values for L (SW 76) were 6 and
      5% lower, respectively, than for D (SW 66). Gain:food was lower (P<0.05) for C
      (SW 69) than for D. ME:GE, wheat AME and ME:gain were not significantly different
      between sites. 7. There was a weak (R2=0.18) positive relationship between ME:GE
      and SW corresponding to a 2.5% increase in energy value for a 10 kg/hl increase
      in SW and no relationship between gain:food and SW. When variety was taken into
      the regression the slope was similar but R2 increased to 0.82. 8. ME:GE and wheat
      AME concentration were negatively correlated with wheat in vitro viscosity
      (R2=0.64, 0.55, respectively). 9. It was concluded that in vitro viscosity
      appears to provide a better basis than SW for prediction of the nutritive value
      of wheats of unknown variety. If the variety is known then SW could be used to
      predict energy value. However, the effect of quite a large change in SW (10
      kg/hl) was relatively small.

PMID- 12047091
TI  - Re-evaluation of calcium and phosphorus requirements in aged laying hens.
AB  - 1. A series of 5 trials was conducted with 401- to 650-d-old Lohmann, Yafa (local
      breed with brown eggshells) and Yarkon (local breed with white eggshells) hens
      fed for 56 to 84 d with diets containing 25 to 50 g/kg calcium (Ca) and 4.5 to
      7.6 g/kg phosphorus (P). 2. Increasing dietary Ca from 24-25 to 36-40 g/kg
      improved egg production, shell weight (SW) and shell thickness (ST), and
      decreased mortality. 3. Increasing dietary Ca to 48 to 50 g/kg did not affect egg
      production but increased SW and/or ST. In one out of the 4 trials, this effect
      was not significant, most likely because of the high shell quality of the eggs
      from the Yafa hens used for this trial. 4. Dietary P content of 4.5 g/kg (1.0
      g/kg added inorganic P) appears to be sufficient for maintaining egg production
      and shell quality in aged laying hen given 36 to 40 g/kg Ca. 5. Increasing
      dietary Ca above 40 g/kg may require a higher dietary P content.

PMID- 12047092
TI  - Effects of dietary chitosan on fat deposition and lipase activity in digesta in
      broiler chickens.
AB  - 1. The effect of dietary chitosan on fat deposition and lipase activity in the
      small intestinal contents was investigated in broiler chickens fed an adequate or
      high metabolisable energy (ME) diet. 2. Male broiler chickens at 14 d old were
      fed on the adequate or high ME diet supplemented with 0 or 50 g/kg chitosan,
      which has a low viscosity, for 3 weeks. 3. Dietary chitosan did not affect food
      intake, body weight gain or food efficiency in either dietary ME groups. 4.
      Dietary chitosan reduced the excessive abdominal fat deposition induced by the
      high ME diet. 5. Dietary chitosan increased the weight of intestinal contents
      irrespective of dietary ME concentration. 6. Dietary chitosan decreased the
      lipase activity per g of small intestinal contents. 7. These results suggest that
      dietary chitosan with low viscosity decreases lipase activity and fat absorption
      in the small intestine, consequently resulting in a reduction of fat deposition
      in broiler chickens. 8. It was concluded that dietary chitosan with low viscosity
      can decrease body fat deposition without reducing food intake and body weight
      gain in broiler chickens.

PMID- 12047093
TI  - Effect of enzyme supplementation of a rye-based diet on xylanase activity in the
      small intestine of broilers, on intestinal crypt cell proliferation and on
      nutrient digestibility and growth performance of the birds.
AB  - 1. A study was undertaken to investigate the susceptibility to peptic digestion
      of exogenous xylanase (EC 3.2.1.8) from Trichoderma longibrachiatum, added to a
      rye-based diet for broiler chickens, in order to elucidate its possible site of
      action. 2. It was also designed to investigate the effects of the enzyme (plus
      exogenous protease EC 3.4-24.28) when added to a rye-containing diet (60% rye/kg
      diet) on crypt cell proliferation in the mucosa of the small intestine, on short
      chain fatty acid (SCFA) concentrations in the small intestine digesta and in
      portal blood and on nutrient digestibilities. 3. In Experiment 1, the enzymes
      were added at activities 10x and 30x those recommended in commercial practice,
      but in Experiment 2 the activities were the recommended levels. 4. A significant
      proportion (estimated to be 15 to 20%) of the xylanase added at the higher
      concentration (15,000 and 45,000 units/kg diet) remained active in the small
      intestine of the growing chicken. 5. The crypt cell proliferation rate in birds
      fed on the control diet (45 cells/2 h) was significantly higher than in birds fed
      on the diets supplemented with enzyme at the higher level (29 and 33 cells/ 2 h),
      but there was no significant effect on SCFA. In birds fed on the diet
      supplemented with enzyme at the commercial level there was no clear-cut effect on
      crypt cell proliferation but exogenous xylanase could be detected in the small
      intestine. Intestinal fluid viscosity was reduced and growth performance of the
      birds was improved by the supplementation with exogenous enzymes. 6. Part of the
      improvement in growth performance could be ascribed to a 25% increase in the
      digestibility of nitrogen and a doubling of the digestibility of fat.

PMID- 12047094
TI  - Dietary levels of chia: influence on hen weight, egg production and sensory
      quality, for two strains of hens.
AB  - 1. Laying hens, 225 white and 225 brown, were fed for 90 d to compare a control
      diet with diets containing 70, 140, 210 and 280 g/kg chia (Salvia hispanica L.)
      seed. 2. Hen weight was not significantly affected by diet; however, manure
      production was less for the hens fed on chia. 3. Egg weight and production, yolk
      weight, and yolk percentage were determined at d 0, 30, 43, 58, 72 and 90. 4. A
      sensory evaluation was conducted on eggs produced during the last week of the
      trial. 5. No significant differences in egg production were found among
      treatments for the brown hens. 6. With the 280 g/kg chia diet, the white hens
      produced fewer and lighter eggs than did the hens fed on the control diet. 7. No
      significant differences were detected in yolk weight until d 90. 8. On this date
      the yolks produced by the white hens fed on the 70 g/kg chia diet were
      significantly lighter in weight, whereas the brown hens produced significantly
      heavier yolks, compared with the hens fed on the control diet. 9. Yolk weight as
      a percentage of egg weight was lower for white hens throughout the trial except
      on d 58 with the 140 g/kg chia diet. Significant differences, however, were
      detected only with the 70 g/ kg chia diet on d 90 and with the 210 g/kg chia diet
      on d 58, 72 and 90. 10. No significant differences in taste preference or flavour
      were found among any of the chia treatments and the control.

PMID- 12047095
TI  - Response of broiler chicks to dietary Rhazya stricta and Nigella sativa.
AB  - 1. Rhazya stricta leaves and Nigella sativa seeds were fed to 7-d-old Hibro
      broiler chicks at 20 and 100 g/kg of the diet for 7 weeks. Although 20 and 100
      g/kg N. sativa seed diets did not adversely affect growth, a decrease in body
      weight and feed efficiency and hepatonephropathy were observed in the chicks fed
      on the 100 g/kg R. stricta diet. 2. These changes, associated with macrocytic
      hypochromic anaemia, were correlated with alterations in serum aspartate
      transaminase' (AST) and alanine transaminase (ALT) activities and concentrations
      of total protein, albumin, globulin, cholesterol, calcium and other serum
      constituents. 3. The effect of 20 g/kg R. stricta diet on chicks was not
      associated with development of biliary hyperplasia or catarrhal enteritis after 7
      weeks of treatment.

PMID- 12047096
TI  - Interactions of dietary polyunsaturated fatty acids and vitamin E with regard to
      vitamin E status, fat composition and antibody responsiveness in layer hens.
AB  - 1. Effects of dietary polyunsaturated fatty acids (PUFA) and vitamin E (VE) on an
      immune response may interact because VE may protect PUFA from in vivo oxidation.
      The present study was designed to study the presence of such an interaction in
      growing layer chickens. 2. Three dietary concentration of linoleic acid (LA, 3.3,
      6.6 and 10%), in combination with 4 concentration of dietary VE (5, 20, 40 and 80
      mg/kg) were used. Effects of LA and VE on circulating VE concentration, fatty
      acid composition of bursal and adipose fat, and antibody kinetics against keyhole
      limpet hemocyanin and Mycobacterim butyricum were established. 3. At high dietary
      LA concentration, bursal and adipose LA were higher but bursal arachidonic acid
      and long chain n-3 PUFA decreased. The dietary VE level did not consistently
      affect the deposition of PUFA in tissue. Plasma VE concentrations were affected
      by the dietary VE and LA content, but not by their interaction. Antibody
      responses before and 7 d after immunisation were affected by the dietary
      treatments. Antibody concentration were not affected by tissue fatty acid
      content. 4. In conclusion, the interaction effects of dietary PUFA and VE on fat
      deposition and immune responses are of minor importance compared to separate PUFA
      and VE effects. This implies that, within the studied range, adding extra VE to
      preserve or affect the effects of dietary PUFA on antibody responsiveness is
      unnecessary.

PMID- 12047097
TI  - Pulmonary arterial pressure and electrocardiograms in broiler chickens infused
      intravenously with L-NAME, an inhibitor of nitric oxide synthase, or sodium
      nitroprusside (SNP), a nitric oxide donor.
AB  - 1. Broilers were divided at 42 to 44 d of age into a Control group (n=30) and a
      Treatment group (n=30). The mean pulmonary arterial pressure (mPAP) and
      electrocardiogram (ECG) leads II and aV(F) were measured 1, 2 and 4 h after an
      intravenous injection of 0.9% saline (Control group) or Nomega-nitro-L-arginine
      methyl esther (L-NAME), an inhibitor of nitric oxide synthase and thus an
      inhibitor of endothelial nitric oxide (NO) production (Treatment group). 2. At 1
      and 2 h but not 4 h post-injection, L-NAME significantly increased the mPAP and
      the amplitudes of the ECG S-wave and RS-wave leads II and aVF when compared with
      Control values. 3. The correlation coefficients between the mPAP and the ECG S
      wave and RS-wave amplitudes for lead II within the Treatment group were -0.848
      and -0.553 at 1 h and -0.798 and -0.512 at 2 h, respectively. The corresponding
      coefficients for lead aVF were -0.735, -0.596, -0.663 and -0.724, respectively.
      4. After suitable mPAP and ECG values had been recorded at each time interval,
      sodium nitroprusside (SNP), which acts as a short-lived NO donor molecule, was
      injected intravenously via a right-cardiac catheter. Within 5 min after the SNP
      injection, the mPAP and the ECG lead II S-wave and RS-wave amplitudes were
      transiently reduced to levels that, at 1 and 2 h after L-NAME injection, did not
      differ from Control values. Within 10 min after the SNP injection, all values
      returned to the levels previously induced by L-NAME. 5. These results demonstrate
      that L-NAME increased the myocardial contractility and PAP, whereas SNP
      transiently reversed the effects of L-NAME on myocardial contractility and PAP.
      It appears likely from these results that the pulmonary vascular endothelium
      releases NO that in turn reduces the pulmonary vascular resistance or attenuates
      myocardial contractility in broiler chickens.

PMID- 12047098
TI  - Assessment of factor V, VII and X activities, the key coagulant proteins of the
      tissue factor pathway in poultry plasma.
AB  - 1. Assay methods were developed for key components of the tissue factor pathway
      of blood coagulation, namely Factor V, Factor VII and Factor X. Using these
      assays, plasma from healthy laying hens, cockerels and broilers was shown to
      contain functional and equivalent amounts of each of these clotting factors. 2.
      The plasma activities for Factor V, Factor VII and Factor X can only be
      accurately determined when chicken tissue factor is used to initiate the
      coagulation mechanism in poultry plasma. Neither human tissue factor nor rabbit
      tissue factor forms a fully functional enzyme reactive complex with chicken
      Factor VII. 3. The overall tissue factor pathway coagulation mechanism was
      evaluated in plasma from laying hens, cockerels and broilers using the one-stage
      prothrombin time assay. As long as sufficient tissue factor was used, the overall
      clotting time results obtained with human recombinant tissue factor were not
      significantly different from those obtained with chicken tissue factor. 4. We
      conclude that poultry plasma does possess a fully functional tissue factor
      coagulation mechanism, but homologous chicken tissue factor must be used for in
      vitro assays of the components of this pathway.

PMID- 12047099
TI  - Quantification of digesta flow into the caeca.
AB  - 1. A caecal intubation technique was developed to determine the amount of digesta
      that enters the caeca of fed and feed-deprived chickens. 2. Dry matter intakes
      per day for control and caecostomised chickens were not significantly different.
      3. For fed and feed-deprived roosters, water intake was significantly increased
      by caecostomy in control birds and was significantly increased by feeding. 4.
      Amount of caecal dry matter excretion was significantly increased by feeding, but
      no difference in caecal water excretion was observed. 5. The ratio of caecal
      excretion (caecal/total excretion) of dry matter and water tended to decrease in
      response to feeding. 6. It is concluded that dry matter entry into the caeca
      represents 18% or 25% of the total dry matter excretion in fed or feed-deprived
      birds, respectively. Corresponding values for water entry are 17 and 26%.
      Therefore, the caeca play an important role in water balance.

PMID- 12047100
TI  - Complement factor B and the alternative pathway of complement activation in
      bovine milk.
AB  - The contribution of the alternative pathway of complement activation to the
      capacity of normal milk to deposit C3 fragments on bacteria was tested by
      attempting to block C3 deposition with antibodies to the alternative pathway
      component factor B (fB). Factor B was purified and antibodies of the IgY class,
      which does not activate mammalian complement, were obtained from the egg yolk of
      immunized laying hens. These antibodies specifically inhibited the deposition of
      C3. This inhibition and the absence of deposition of C4 demonstrated that C3
      deposition in normal milk resulted from the activation of the alternative
      pathway. Antibodies raised in rabbit were used to develop an ELISA for measuring
      fB concentrations in milk. The mean concentration of fB was 2.06 microg/ml (+/-
      0.18, SEM), 0.57% of the mean value found in serum (360 microg/ml). This
      proportion was comparable to that of serum albumin (0.63% of serum value) but
      less than the proportion of C3 in milk (2.71%). Nevertheless, fB was apparently
      not a limiting factor for the functioning of the alternative pathway, since
      addition of purified fB to normal milk did not improve C3 deposition. In serum,
      mild heat-treatment (56 degrees C for 3 min or 50 degrees C for 45 min) blocked
      the alternative pathway and destroyed fB, as shown by loss of antigenicity in
      ELISA. In milk, mild heat-treatment did not abrogate C3 deposition, and fB was
      protected, retaining its functionality and antigenicity. Heating at 56 degrees C
      for at least 45 min was necessary to completely inhibit C3 deposition in normal
      milk.

PMID- 12047101
TI  - Effect of long-term intake of milk products on blood pressure in hypertensive
      rats.
AB  - The effect of long-term intake of two fermented milk products on the development
      of hypertension was compared in young spontaneously hypertensive rats (SHR). The
      products contained tripeptides isoleucine-proline-proline (IPP) and valine
      proline-proline (VPP), which have been shown to possess angiotensin converting
      enzyme (ACE) inhibitory activity. Six-week-old SHR were divided into four groups
      to receive orally ad libitum water, skim milk or two fermented milk poducts
      (fermented milk A or fermented milk B; the latter is commercially available in
      Japan with trade name Calpis) for 14 weeks. The calculated intake of IPP was 0.4
      mg/d and 0.2 mg/d in the groups receiving fermented milk A and B, respectively,
      whereas the corresponding amounts for VPP were 0.6 mg/d and 0.3 mg/d. Systolic
      blood pressure (SBP) was monitored weekly by tail-cuff method. The development of
      hypertension was significantly attenuated in both groups receiving fermented milk
      products, whereas skim milk did not affect blood pressure. The effect was
      detectable after 6 weeks of treatment. At the end of the experiment, the lowest
      blood pressure level was found in the group receiving fermented milk A: the SBP
      was 21 mm Hg lower than in the group receiving water and 10 mm Hg lower than in
      the group receiving fermented milk B. This difference could be explained by
      larger intake of ACE inhibitory tripeptides in the group receiving fermented milk
      A as compared with fermented milk B.

PMID- 12047102
TI  - Effect of high intensity pulsed electric fields and heat treatments on vitamins
      of milk.
AB  - The effects of high intensity pulsed electric field (HIPEF) treatments at room or
      moderate temperature on water-soluble (thiamine, riboflavin, ascorbic acid) and
      fat-soluble vitamins (cholecalciferol and tocopherol) were evaluated and compared
      with conventional thermal treatments. Vitamin retention was determined in two
      different substrates, milk and simulated skim milk ultrafiltrate (SMUF). Samples
      were subjected to HIPEF treatments of up to 400 micros at field strengths from
      18.3 to 27.1 kV/cm and to heat treatments of up to 60 min at temperatures from 50
      to 90 degrees C. No changes in vitamin content were observed after HIPEF or
      thermal treatments except for ascorbic acid. Milk retained more ascorbic acid
      after a 400 microstreatment at 22.6 kV/cm (93.4%) than after low (63 degrees C-30
      min; 49.7% retained) or high (75 degrees C-15s; 86.7% retained) heat
      pasteurisation treatments. Retention of ascorbic acid fitted a first-order
      kinetic model for both HIPEF and thermal processes. First-order constant values
      varied from 1.8 x 10.4 to 1.27 x 10(-3) micros(-1) for the HIPEF treatments (18.3
      27.1 kV/cm) and, for thermal processing ranged from 5 x 10(-3) to 8 x 10(-2) min(
      1) (50-90 degrees C). No significant differences were found between the results
      obtained after applying HIPEF treatments at room or moderate temperature.
      However, results depended on the treatment media. A beneficial effect of natural
      skim milk components, mainly proteins, was observed on the preservation of
      ascorbic acid, since skim milk retained more ascorbic acid than SMUF after HIPEF
      treatments.

PMID- 12047103
TI  - Evolution of carbohydrate fraction in carbonated fermented milks as affected by
      beta-galactosidase activity of starter strains.
AB  - The influence of carbonation on the evolution of lactose, galactose and glucose
      in fermented milks with added probiotic bacteria (Lactobacillus casei,
      Lactobacillus acidophilus and/or Bifidobacterium bifidum) was evaluated and
      related to beta-galactosidase activity of starter strains. During incubation and
      first days of refrigeration, lactose hydrolysis resulting in the liberation of
      galactose and glucose occurred in CT (Streptococcus thermophilus/Lb. casei), AT
      (Str. thermophilus/Lb. acidophilus) and ABT fermented milks (Str.
      thermophilus/Lb. acidophilus/Bifid. bifidum). Levels of galactose were higher
      than those of glucose and could be related to the preferential consumption of
      glucose by actively growing bacteria. Through the incubation, lactose and
      monosaccharide levels were not affected by milk carbonation. However, during
      refrigerated storage the presence of this gas was associated with slightly lower
      content of lactose and higher levels of galactose and glucose in AT and ABT
      products but not in CT fermented milks. Through the refrigeration galactose was
      moderately utilised by Lb. acidophilus in AT products whereas the presence of
      Bifid. bifidum seems to prevent the consumption of this sugar in ABT fermented
      milks. Glucose remained constant, with minor variations in CT products but a
      continuous increase of this sugar occurred in carbonated AT and ABT fermented
      milks during storage. Beta-galactosidase activity displayed by Str. thermophilus
      strains was similar at pH 6.5 (initial pH of non-carbonated samples) and pH 6.3
      (initial pH of carbonated samples) whereas Lb. acidophilus LaA3 showed greater
      beta-galactosidase activity at pH 6.3 than at higher pH values. Thus, the
      enhanced metabolic activity of Lb. acidophilus caused by the low initial pH of
      carbonated milk also promoted higher cellular beta-galactosidase activity that
      could have released greater amounts of galactose and glucose from lactose in AT
      and ABT fermented milks through the refrigerated period. In CT fermented milks,
      similar beta-galactosidase activity levels of Str. thermophilus at pH 6.5 and 6.3
      together with the absence of beta-galactosidase activity in Lb. casei could
      explain the lack of differences on glucose and galactose content between
      carbonated and non-carbonated samples.

PMID- 12047104
TI  - Developmental expression of pIgR gene in sheep mammary gland and hormonal
      regulation.
AB  - Secretory IgA found in external secretions are constituted by polymeric IgA
      (pIgA) bound to the extra-cellular part of the polymeric immunoglobulin receptor
      (pIgR). The receptor mediates transcytosis of pIgA across epithelial cells. The
      aim of the present study was to analyse the evolution of pIgR expression in the
      sheep mammary gland during the development of the mammary gland and to analyse
      its hormonal regulation. Gene expression of the pIgR was analysed in sheep
      mammary gland during pregnancy and lactation. By Northern Blot analysis, we
      observed that low levels of pIgR mRNA are expressed until day 70 of pregnancy.
      Accumulation of pIgR mRNA started during the third part of pregnancy and
      intensified 3 d after parturition to reach highest levels during established
      lactation (day 70). In situ hybridization analysis was used to confirm the
      increase in pIgR gene expression per mammary epithelial cell. In order to examine
      the hormonal regulation of the pIgR expression, virgin ewes were hormonally
      treated. Treatment with oestradiol and progesterone increased pIgR mRNA levels
      slightly. Subsequent addition of gluocotricoids induced a significant
      accumulation of pIgR mRNA in the mammary gland of the treated animals.
      Immunohistochemical analysis was performed to verify that the increase of pIgR
      mRNA level was associated with enhancement of the pIgR protein in mammary cells.
      No increase of pIgR mRNA levels were observed if PRL secretion was blocked by
      bromocryptine injections throughout the hormonal procedure. In conclusion, the
      present experiments suggest that the enhancement of pIgR levels during lactation
      result from combined effects of both prolactin and glucocorticoids.

PMID- 12047105
TI  - A polyphasic approach to highlight genotypic and phenotypic diversities of
      Lactobacillus helveticus strains isolated from dairy starter cultures and
      cheeses.
AB  - In the present work, 67 strains of Lactobacillus helveticus isolated from whey
      starter cultures and cheeses were identified and grouped by genotypic and
      phenotypic methods. Strains were identified by sugar fermentation pattern, by
      cell-wall protein profile, and by probe hybridisation. Phenotypic diversity was
      evaluated by a chemometric model taking into account biochemical characteristics
      (i.e. acidifying and peptidase activities) of technological interest. Genotypic
      diversity was evidenced by RAPD-PCR, which provided stran-specific patterns and
      revealed the occurrence of different strains. The RAPD-PCR profiles were
      clustered according to their similarities: the groups obtained, together with the
      cell-wall protein profiling and the chemometric information, could be sometimes
      correlated with the type of cheese and/or dairy niches used as sources of
      strains. A computerised analysis of genotypic and phenotypic information could be
      successfully applied for rapid and reliable differentiation and characterisation
      of Lb. helveticus isolates occurring in different dairy products.

PMID- 12047106
TI  - Comparison of electromyographic pattern of sensory experts and untrained subjects
      during chewing of Mahon cheese.
AB  - Use of electromyography (EMG) to monitor mastication is a relatively new concept
      in assessing food physical and sensory properties. Although expert assessment of
      cheese characteristics is widely used, the effect of training in sensory analysis
      on mastication patterns, as assessed using EMG is not well known. Nine samples of
      the same Mahon cheese (60 days ripening) were given to 24 subjects (8 experts, 16
      untrained) and EMG recorded for each chewing sequence. Three samples were tested
      in a single session by each subject, and three sessions carried out on different
      days. EMG was recorded from four masticatory muscles for each subject. From EMG
      records the following was extracted: number of chews, chewing time, mean and
      maximum voltage of EMG bursts (i.e. chews) across chewing sequence, chewing work
      and chewing rate. No gender bias was found for the EMG parameters considered,
      therefore, as regards gender, each group was considered to be homogeneous.
      Variability within-subjects across samples was greater for experts than untrained
      subjects. Significant differences in chewing time, chewing work and chewing rate
      were found between the expert and untrained groups. Data analysis of the three
      sessions showed an influence of cognitive constructs, mediating states, on the
      chewing process. The experts were found to be goal driven as to their mastication
      process. Experts showed no significant differences between sessions, untrained
      subjects were found to vary their EMG output in successive sessions for number of
      chews, chewing time, mean voltage, and chewing work.

PMID- 12047107
TI  - Evaluation of volatile compounds in different types of ghee using direct
      injection with gas chromatography-mass spectrometry.
AB  - Desi ghee (DG) was prepared from fermented cream followed by heat clarification
      (desi method) in the laboratory and butter oil (BO) was prepared from fresh
      butter by melting and centrifugation. Fresh samples of three brands of industrial
      ghee (IG-1, IG-2, IG-3) were collected from the local market. Volatile compounds
      of desi and industrial ghee and butter oil were isolated and concentrated using
      direct injection and cryofocussing techniques; separation and identification was
      by Gas Chromatography Mass Spectrometry (GCMS). A maximum of 36 compounds were
      detected in desi ghee whereas compounds detected in three industrial ghee samples
      varied from 22-29. The lowest number of compounds (16) was detected in butter
      oil. Of the identified compounds, maltol, 5-hydroxymethyl furfuraldehyde,
      dihydrodihydroxypyranone, 1,3-butanediol and 1-octanol were identified only in
      desi ghee volatiles. The concentration of acetic acid was found to be remarkably
      higher in desi ghee volatiles than in industrial ghee. Also the levels of
      identified fatty acids, methyl ketones, aldehydes, lactones and alcohols were
      high in desi ghee volatiles compared with industrial ghee and butter oil. In
      total, 62 compounds were detected, which included 6 aldehydes, 12 ketones, 8 each
      of fatty acids, alcohols and lactones, 4 each of esters and hydrocarbons or other
      compounds, and 12 compounds remained unidentified.

PMID- 12047108
TI  - Development and validation of a nephelometric immunoassay for IgG1 in milk.
AB  - A nephelometric immunoassay, with a detection range of 0.3 to 5 g IgG1/l, was
      (leveloped for the determination of immunoglobulin in bovine milk. The assay
      exhibited no significant cross-reactivity with alphas1-casein, alphas2-casein,
      beta-casein, K-casein or beta-lactoglobulin and 39% cross-reactivity with IgG2.
      The nephelometric assay was compared with ELISA and RID (24 h and 48 h
      incubations) assays using 105 duplicate milk samples covering IgG1 values ranging
      from 0.45 to 1.8 g. The results obtained from all assays showed good agreement
      with the exception of those obtained by the RID assay (24 h incubation) which
      gave lower results in samples containing more than 1.2 g IgG1/l. It was concluded
      that the nephelometric assay is a reliable, rapid and convenient method suitable
      for the quantification of IgG1 in milk. The assay can be configured for routine
      high-throughput milk quality assurance for IgG1 in dairy laboratories.

PMID- 12047109
TI  - Mammary apoptosis and lactation persistency in dairy animals.
AB  - The decline in milk yield after peak lactation in dairy animals has long been a
      biological conundrum for the mammary biologist, as well as a cause of
      considerable lost income for the dairy farmer. Recent advances in understanding
      the control of the mammary cell population now offer new insights on the former,
      and a potential means of alleviating the latter. The weight of evidence now
      indicates that a change in mammary cell number, the result of an imbalance
      between cell proliferation and cell removal, is a principal cause of declining
      production. Further, it suggests that the persistency of lactation, the rate of
      decline in milk yield with stage of lactation, is strongly influenced by the rate
      of cell death by apoptosis in the lactating gland. Mammary apoptosis was first
      demonstrated during tissue involution after lactation, but has now been detected
      during lactation, in mammary tissue of lactating mice, goats and cattle. Those
      factors that determine the rate of cell death by apoptosis are as yet poorly
      characterized, but include the frequency of milking in lactating goats. Initial
      evidence suggests that nutrition also is likely to influence cell survival after
      peak lactation, an important factor being the degree of oxidative stress imposed
      by feed and the tissue's ability to deal with, and prevent damage by, reactive
      oxygen species. Comparison of cows in calf or not pregnant during declining
      lactation also indicates a likely influence of reproductive hormones, with
      oestradiol and progesterone acting to preserve mammary ductal and alveolar
      integrity during the dry period, while allowing a degree of apoptosis and cell
      replacement. In each case, the molecular mechanisms controlling mammary cell
      survival (or otherwise) are as yet poorly defined. On the other hand, more
      persistent lactations are likely to benefit animal welfare through fewer calvings
      and by placing less emphasis on maximal production at peak lactation, and
      modelling of persistent lactation with longer calving intervals indicates their
      likely economic benefits. In these circumstances, there is considerable incentive
      to elucidate the determinants of mammary apoptosis, and the factors controlling
      the dynamic balance between cell proliferation and cell death in the lactating
      mammary gland.

PMID- 12047110
TI  - Factors affecting test-day milk composition in dairy ewes, and relationships
      amongst various milk components.
AB  - A total of 7492 test-day observations for mean contents of fat, protein, casein,
      serum protein and lactose and individual laboratory cheese yield (ILCY) were
      obtained, at approximately monthly intervals, from 1119 ewes belonging to eight
      Churra dairy flocks. The effect of various factors on these variables was
      examined and phenotypic correlations among all traits were estimated. Least
      squares analyses showed significant effects of flock test-date, stage of
      lactation, age of ewe, and number of lambs weaned on almost all variables.
      Protein content and composition were not affected by the number of lambs weaned.
      ILCY had an unadjusted mean (26-55 kg cheese/100 l milk) close to those reported
      for real cheese yield in dairy ewes and was affected similarly to the main milk
      components. Fat, protein, casein, and serum protein contents, and ILCY, showed a
      generally increasing trend as lactation progressed. These components reached a
      minimum at 1 month into lactation, when milk yield was highest, and increased for
      the remainder of the lactation. ILCY depended mainly on fat, protein and casein
      contents. Protein and casein contents were closely related and equally correlated
      with ILCY. An increase in somatic cell count (SCC) was associated with decreased
      milk yield and decreased lactose content.

PMID- 12047111
TI  - Inhibition of oxytocin release during repeated milking in unfamiliar
      surroundings: the importance of opioids and adrenal cortex sensitivity.
AB  - The aim of this study was to test if the opioid antagonist naloxone has a
      beneficial effect on normalization of oxytocin (OT) release during repeated
      milking of cows in unfamiliar surroundings. One control milking without naloxone
      treatment in all cows was performed in the familiar parlour. For four successive
      evening milkings, cows were transported to, and milked in, the operating theatre
      of the research station without (control group) or with naloxone administration
      (1 mg/kg BW) (naloxone group) before milking. After cessation of spontaneous milk
      flow, but not before 3 min of milking, vaginal stimulation was applied for 2 min.
      After milk flow ceased again, 10 IU of OT was injected intravenously to remove
      the remaining milk including residual milk. Milk flow was recorded continuously
      and blood samples were collected via a jugular vein cannula at 1-min intervals
      from 1 min before the start of milking until i.v. injection of OT. The inhibition
      of milk ejection and its normalization during repeated milking in unfamiliar
      surroundings was not influenced by naloxone treatment. Concentrations of cortisol
      and beta-endorphin during control milking and all relocations were similar in the
      naloxone and control groups, although their concentrations were higher after
      relocations than in the control. Therefore, a role of endogenous opioids in the
      inhibition of milk ejection in unfamiliar surroundings could not be demonstrated.
      In addition, the effect of exogenous ACTH1-24 (8 IU, i.v.) on the release of
      cortisol related to the response of cows milked in unfamiliar surroundings was
      studied. Cows with totally inhibited milk ejection in response to vaginal
      stimulation during milking after first relocation had numerically, but not
      significantly lower cortisol levels (8.8+/-3.4 ng/ml; AUC/min) in response to
      ACTH than did cows with at least partial milk ejection (38.7+/-12.9 ng/ml). Thus
      animals with a higher adrenal response to ACTH seemed to have less severe
      inhibition of milk ejection.

PMID- 12047113
TI  - Effect of over-milking on teat condition.

PMID- 12047112
TI  - Performance differences and cow responses in new milking parlours.

PMID- 12047114
TI  - Structural features of bovine caseinomacropeptide A and B by 1H nuclear magnetic
      resonance spectroscopy.
AB  - Samples of bovine caseinomacropeptide (CMP) were isolated from kappa-casein A and
      kappa-casein B and fractionated to give aglycosylated CMP A and CMP B and
      monoglycosylated CMP A. The secondary structures of these three peptides were
      compared under neutral and acidic (pH 4.2) conditions, using two-dimensional (2D)
      1H nuclear magnetic resonance (NMR) spectroscopy. The differences between the
      spectra at pH 4.2 and 7.0 and the spectra of the aglycosylated and glycosylated
      CMP A were subtle, indicating little change in backbone conformation with these
      changes. These results Suggest that differences in the coagulation properties of
      milks containing either kappa-casein A or kappa-casein B are more likely to be
      related to factors, such as micelle size or charge, than to structural
      differences arising from altered backbone conformation of the macropeptide
      segments of the kappa-caseins.

PMID- 12047115
TI  - 15N as a marker to assess portal absorption of nitrogen from milk, yogurt and
      heat-treated yogurt in the growing pig.

PMID- 12047117
TI  - The tragedy behind the wounds.

PMID- 12047116
TI  - Are we guilty of unethical selling?

PMID- 12047118
TI  - Maintaining standards.

PMID- 12047119
TI  - Maintaining standards II.

PMID- 12047120
TI  - Toss-up over the euro.

PMID- 12047122
TI  - Crowns and other extra-coronal restorations: cores for teeth with vital pulps.
AB  - Cores for teeth with vital pulps is the seventh in the series of crowns and other
      extra-coronal restorations. A core is defined as 'that part of a preparation for
      an indirect restoration consisting of restorative material'. This article
      questions the need for routine pin placement and addresses the following issues-
      removal of existing restorations, the need for a core, core materials, core
      retention, and problem solving.

PMID- 12047123
TI  - An investigation of paediatric dentists' attitudes towards parental accompaniment
      and behavioural management techniques in the UK.
AB  - OBJECTIVE: Good behavioural management techniques are essential for treating
      children. Recent research has investigated parental and paediatric attitudes
      towards various behavioural management techniques. However, in the UK, very
      little is known about paediatric attitudes towards such issues. Accordingly, the
      aim of this investigation was to conduct a survey in order to provide insight
      into the current thinking of paediatric dentists across the UK. STUDY DESIGN: A
      questionnaire was developed for this study on the basis of previous surveys
      investigating the attitudes of paediatric dentists towards the use of various
      behavioural management techniques in Australia and the USA. Areas covered in the
      questionnaire included: attitudes towards parental accompaniment; attitudes
      regarding parental expectations; and attitudes towards the use of various
      different child management techniques. The questionnaire was sent out to all
      registered members of the British Society of Paediatric Dentistry (n = 304).
      RESULTS: 245 responses (80.5%) were returned, of which 218 provided valid and
      useable information (72%). A majority of 80% of respondents supported parental
      accompaniment of the child during the course of treatment. Separate analysis of
      variance (ANOVA) procedures revealed significant differences between
      acceptability of parental accompaniment and the year in which dentists had
      qualified (P < 0.05). More recently qualified dentists were less accepting of
      parental accompaniment. Only a minority of dentists reported feeling pressured by
      parental expectations with regard to their child's treatment. However, an
      independent sample t-test revealed that male dentists experienced greater
      perceived conflict between dental and parental expectations, than female dentists
      (P < 0.05). In terms of specific behavioural management techniques, the most
      favoured was 'tell-show-do' with 87% of respondents citing this as their most
      commonly used method. Least acceptable were 'hand over mouth' techniques,
      followed closely by active restraint and papoose board. CONCLUSION: In general,
      paediatric dentists in the UK favoured less 'restraining' methods of behavioural
      management. There was widespread support for parental accompaniment in the dental
      operatory and a desire to work in participation with parents in order to
      facilitate the child's good behaviour and more effective dental treatment.
      Further studies comparing the effectiveness of various techniques used with
      regard to treatment time and clinical outcomes, are now required.

PMID- 12047121
TI  - The York review--a systematic review of public water fluoridation: a commentary.
AB  - Following the election of the British government in May 1997, a policy document
      outlining proposals to improve the health of the nation was published. This
      document placed a major emphasis on reducing inequalities in health and
      recognised the continuing poor state of oral health in deprived communities.
      However, whilst acknowledging the benefits of water fluoridation as a caries
      preventive measure, the Department of Health suggested that most of the research
      had been carried out some years ago and furthermore, recognised that strong views
      were held both for and against fluoridation.

PMID- 12047124
TI  - Physiognomy and teeth: an ethnographic study among young and middle-aged Hong
      Kong adults.
AB  - OBJECTIVES: To determine knowledge and beliefs about traditional physiognomy
      (judging an individual's character from their facial appearance) concerning teeth
      among young (17-26) and middle-aged (35-44) Hong Kong adults. METHODS: In a cross
      sectional ethnographical telephone survey, 400 adults were interviewed about 16
      traditional physiognomy concerning teeth (in consultation with a Feng Shui
      specialist). RESULTS: Most completed the interview (93%, 373). Over half the
      study group (63%, 234) claimed they had heard of aspects of physiognomy
      concerning teeth, and a quarter (24%, 88) believed in such ideologies. Variations
      in knowledge and beliefs were apparent among people of different age (P < 0.01),
      gender (P < 0.05), educational attainment (P < 0.01), economic status (P < 0.01),
      place of birth (P < 0.01) and religion (P < 0.01). Their knowledge and belief in
      aspects of physiognomy concerning teeth was also associated with reported use of
      dental services (P < 0.01). CONCLUSION: Among young and middle-aged adults in
      Hong Kong, knowledge and beliefs concerning traditional physiognomy regarding
      teeth is strong, and socio-demographic variations exist in these perceptions.
      These findings have implications for all those involved in the delivery of dental
      care in multicultural societies and in raising cultural awareness about
      traditional health beliefs.

PMID- 12047126
TI  - Ooh! Grab one of those, quick.
AB  - It is unlikely that you will ever have come away from a dental congress,
      conference or even the most humble of meetings without something 'free' in your
      hand. But what do you do with it then?

PMID- 12047127
TI  - Population and health: achievements and challenges.

PMID- 12047125
TI  - Dental erosion in a group of British 14-year-old, school children. Part III:
      Influence of oral hygiene practises.
AB  - OBJECTIVES: The aims of this study were firstly to describe the dental history
      and oral hygiene practises in a cluster random sample of 14-year-old children in
      Birmingham, UK. The second aim was to determine whether the oral hygiene
      practises are associated with dental erosion. METHOD: A total of 418, 14-year-old
      schoolchildren from a cluster random sample in Birmingham, UK were assessed for
      dental erosion (209 males and 209 females). Data on the dental history and oral
      hygiene practises were obtained from a self-reported questionnaire supplemented
      by a structured interview. The data were analysed using SPSS with Mann-Whitney U
      analyses and odds ratios. RESULTS: 74% of the teenagers claimed to attend the
      dentist on a six-monthly basis; 60% brushed their teeth twice a day ie before
      breakfast and last thing at night, 25% once a day, 12% three times or more a day
      and 3% less than once a day. It was a so found that 28% of the children brushed
      their teeth after meals; 92% of the children used a manual toothbrush and 56% of
      them replaced their toothbrush every three-months. The most common technique used
      by the children was a circular brushing movement; 44% of them used a mouthwash
      and 40% used other interdental cleaning. Girls brushed their teeth more
      frequently than boys. Associations were found between dental erosion and brushing
      teeth last thing at night, after meals, techniques of brushing teeth, and type of
      toothbrush and frequency of brushing. It was concluded that reported oral hygiene
      practises in teenage schoolchildren in Birmingham, UK complied with generally
      recommended guidelines. However, there was an association between dental erosion
      and some of these oral hygiene practises. Advice concerning the impact of some
      oral hygiene procedures needs to be given to those who are susceptible to dental
      erosion.

PMID- 12047128
TI  - Deficit of women in India: magnitude, trends, regional variations and
      determinants.

PMID- 12047129
TI  - Basic amenities and health in urban India.
AB  - We have examined the findings from various studies and corroborated other
      evidence that the large and continuous increase in India's urban population, and
      the concomitant growth of the population residing in slums and shanty towns, has
      resulted in over-straining of infrastructure and a deterioration in public
      health. Inadequate civic amenities, lack of purchasing power, and lack of
      knowledge and awareness among the urban poor have resulted in urban poverty which
      is very different from its rural counterpart. While a few policies have
      specifically targeted the urban poor, these have been neither sufficient nor
      effective. Also, the deteriorating health status of urban people needs urgent
      attention because many of the recent health problems can take an epidemic form if
      neglected. A resurgence of malaria, dengue and tuberculosis indicates that much
      of the poor health emanates from a lack of basic amenities such as sanitation,
      clean water and housing, coupled with a lack of awareness about the need to take
      precautionary measures against preventable and infectious diseases. To tackle
      these problems effectively, it is important for policy-makers to recognize that
      certain groups are more susceptible to ill health than others; they are
      vulnerable to the severe impact of illnesses and also the likely sources of
      infection for the population at large. There is an urgent need for research on
      the factors that prevent the urban poor from availing the services provided to
      them. It is possible that this is due to the lack of awareness-generating
      policies which should accompany any supply-side policies such as the provision of
      basic facilities (e.g. Sulabh Sauchalaya). To reduce the private costs as well as
      the negative externalities of ill health, it may be necessary to target such
      populations by cost-effective strategies based on holistic research on all the
      factors that determine well-being.

PMID- 12047130
TI  - Demographic trends: the last 50 years.

PMID- 12047131
TI  - Avoidable mortality in India: past progress and future prospects.

PMID- 12047132
TI  - Health transition in India: issues and challenges.

PMID- 12047133
TI  - Population policy in India: evolution, performance and challenges.

PMID- 12047134
TI  - Thrombopoietin administered during induction chemotherapy to patients with acute
      myeloid leukemia induces transient morphologic changes that may resemble chronic
      myeloproliferative disorders.
AB  - Thrombopoietin (TPO), a potent stimulator of megakaryocyte and platelet
      production, has been used in clinical trials to reduce thrombocytopenia after
      chemotherapy in patients with acute myeloid leukemia (AML). We report that TPO
      therapy is associated with peripheral blood and bone marrow findings that can
      mimic myeloproliferative disorders. Peripheral blood and bone marrow samples of
      13 patients with AML who received TPO were examined. A subset of bone marrow
      samples exhibited hypercellularity, megakaryocytic hyperplasia, and reticulin
      fibrosis after TPO administration. Cases demonstrated as many as 58.4
      megakaryocytes per high-powerfield (MHPF) compared with 3.7 MHPF in the control
      group. Megakaryocytic atypia, increased mitoses, emperipolesis, intrasinusoidal
      megakaryocytes, and thickened trabeculae also were seen. Peripheral blood
      findings included leukoerythroblastosis, leukocytosis, thrombocytosis, and
      circulating megakaryocyte nuclei. Changes resolved within 3 months after
      discontinuation of TPO. This rapid resolution of the morphologic abnormalities
      induced by TPO distinguishes these findings from those seen in true chronic
      myeloproliferative disorders.

PMID- 12047135
TI  - Probability-based construction of reference ranges for ratios of log-gaussian
      analytes: an example from automated leukocyte counts.
AB  - Reference ranges (RRs) are frequently used for interpreting laboratory values in
      clinical trials, assessing abnormality of laboratory results, and combining
      results from different laboratories. When a clinical laboratory measure must be
      derived from other tests, eg, the WBC differential percentage from the WBC count
      and WBC differential absolute count, a derivation of the RR may also be required.
      A naive method for determining RRs calculates the upper and lower limits of the
      derived test from the upper and lower limits of the measured values using the
      same algebraic formula used for the derived measure. This naive method and any
      others that do not use probability-based transformations do not maintain the
      distributional characteristics of the RRs. RRs derived in such a manner are
      deemed uninterpretable because they do not contain a specific proportion of the
      distribution. We propose a probability-based approach for the interconversion of
      RRs for ratios of 2 log-gaussian analytes. The proposed method gives a simple
      algebraic formula for calculating the RRs of the derived measures while
      preserving the probability relationships. The nonparametric method and a
      parametric method that takes the log transformation, estimates an RR, and then
      exponentiates are provided as comparators. An example that compares the commonly
      used naive method and the proposed method is provided on automated leukocyte
      count data. This provides evidence that the proposed method maintains the
      distributional characteristics of the transformed RR measures while the naive
      method does not.

PMID- 12047136
TI  - Flow cytometric measurement of hemoglobin F in RBCs: diagnostic usefulness in the
      distinction of hereditary persistence of fetal hemoglobin (HPFH) and hemoglobin S
      hPFH from other conditions with elevated levels of hemoglobin F.
AB  - The cellular distribution of hemoglobin F is important for evaluating
      persistently elevated hemoglobin F levels, such as in hereditary persistence of
      fetal hemoglobin (HPFH) or delta/beta-thalassemia, and for differentiating
      homozygous hemoglobin S (or hemoglobin S-beta(0)-thalassemia) from hemoglobin S
      HPFH, traditionally done by using the Kleihauer-Betke (K-B) acid elution test. We
      evaluated a flow cytometric method using an anti-hemoglobin F antibody as a
      replacement for the K-B test. We used 172 specimens representing a variety of
      conditions: HPFH trait, 19 cases; delta/beta-thalassemia trait, 8 cases;
      hemoglobin S-HPFH, 10 cases. By flow cytometry, all cases of HPFH trait gave a
      hemoglobin F pattern comparable to the homocellular pattern obtained by the K-B
      test; all cases of delta/beta-thalassemia tested gave a pattern comparable to a K
      B heterocellular pattern. Most cases of hemoglobin S-HPFH gave a homocellular
      distribution of hemoglobin F whereas all cases of homozygous hemoglobin S with
      elevated hemoglobin F levels gave a heterocellular pattern. Flow cytometry
      provides a more rapid and objective method for assessing cellular distribution of
      hemoglobin F and is useful for patient evaluation when HPFH trait, delta/beta
      thalassemia trait, or hemoglobin S-HPFH trait is suspected.

PMID- 12047137
TI  - Clonal heterogeneity assessed by flow cytometry in B-cell lymphomas arising from
      germinal centers.
AB  - Patients with mature follicular B-cell lymphomas develop aggressive non-Hodgkin
      lymphomas (NHLs) during disease progression. It is controversial whether most
      diffuse large B-cell lymphomas (DLBCLs) and Burkitt lymphomas (BLs) emerge as de
      novo lymphomas or from an original follicular lymphoma. To distinguish clonally
      related populations in aggressive NHL, we studied the immunophenotypic features
      of 18 consecutive samples from 16 patients. Three flow cytometric patterns were
      distinguished: (1) a homogeneous neoplastic population of large B cells with
      phenotypic features of follicular center cells; (2) 2 atypical populations of B
      cells, small monoclonal B cells, and large B cells with loss of some surface
      antigens; and (3) 2 clonal populations of small and large B cells sharing the
      same light-chain isotype. The 3 flow cytometric patterns were observed,
      respectively, in de novo DLBCL and BL, transformation into BL, and transformation
      into DLBCL. Flow cytometric data can provide valuable information about the
      natural history of NHL.

PMID- 12047138
TI  - Five fully automated methods for performing immature reticulocyte fraction:
      comparison in diagnosis of bone marrow aplasia.
AB  - We performed a parallel evaluation of 5 automated reticulocyte counters to
      produce the immature reticulocyte fraction (IRF). We analyzed 225 samples from
      healthy control subjects, 115 from patients with various diseases, 38 with
      advanced aplasia, and 22 in early erythropoietic recovery after chemotherapy or
      bone marrow transplantation. The reference intervals were different for each
      instrument (ADVIA 120, 0.04-0.25; CELL DYN 4000, 0.15-0.35; GEN-S, 0.20-0.37; SE
      9500 RET 0.05-0.21; VEGA RETIC: 0.06-0.23). The imprecision, obtained by 1-way
      analysis of variance on duplicates, was satisfactory for clinical use for all
      methods (coefficient of variation, 7.6%-20.5% in healthy subjects), although it
      was higher than the analytic goal based on biologic variability within subjects.
      The comparison of different methods shows that agreement is good only between SE
      9500 RET CELL DYN 4000, and VEGA RETIC (r2 = 0.72-0.78). The study of diagnostic
      performance in distinguishing aplasia from early bone marrow recovery shows
      slightly different results (area under the curve from 0.70 for ADVIA 120 to 0.96
      for SE 9500 RET). Even with slight differences, the fluorescence-based methods
      seem to be more robust than other methods for IRF measurement.

PMID- 12047139
TI  - Fine-needle aspiration in non-Hodgkin lymphoma: evaluation of cell size by
      cytomorphology and flow cytometry.
AB  - We studied 48 non-Hodgkin lymphoma (NHL) fine-needle aspiration (FNA) specimens
      with initial cytomorphology (CM) and flow cytometry (FC) and subsequent surgical
      biopsy of the same lesion to determine whether a reliable diagnosis of large cell
      lymphoma or large cell transformation could be made. CM was evaluated by
      examining 200 lymphocytes in each specimen. FC was performed by analyzing
      monoclonal or abnormal B-cell populations. Percentages of large cells were
      evaluated by CM and FC and results correlated with the histologic diagnosis. All
      small cell NHLs showed fewer than 40% large cells by CM and FC; 100% (9/9; FC)
      and 67% (6/9; CM) of diffuse large B-cell lymphomas demonstrated greater than 40%
      large cells. Variable numbers of large cells were detected in grade III
      follicular lymphoma, low-grade lymphoma with partial large cell transformation,
      and large B-cell lymphoma containing fewer than 10% neoplastic cells. By using
      combined CM and FC, large cell lymphoma and large cell transformation can be
      diagnosed reliably by FNA if greater than 40% large cells are present. Surgical
      biopsy is necessary when there is necrosis, fewer than 10% neoplastic cells by
      FC, or fewer than 40% large cells with clinical signs of transformation.

PMID- 12047140
TI  - Minimum numbers of fresh whole blood and plasma samples from patients and healthy
      subjects for ISI calibration of CoaguChek and RapidPointCoag monitors.
AB  - The international sensitivity index (ISI) calibration of point-of-care-test
      (POCT) prothrombin time (PT) whole blood monitors is complex, requiring manual PT
      testing of 60 patients' and 20 healthy subjects' plasma samples. The possibility
      of reducing these numbers was studied by a Monte Carlo Bootstrap study for 2 POCT
      PT systems. For reduced sample numbers, this consisted of 50,000 calibrations
      using whole blood and plasma samples tested on the monitors with manual PT
      testing of plasma samples from the same blood donations. There was little effect
      on mean ISI by reduction of sample numbers to a total of 7, but there was
      progressively less certainty regarding the reliability of the calibration.
      Precision of the calibrations and international normalized ratio deviation were
      not affected markedly by reducing numbers to half As ISI calibration with the 2
      POCT systems was less precise than conventional manual testing, for maximum
      confidence, reduction of numbers is not advised.

PMID- 12047141
TI  - Development of a high-pressure liquid chromatography method for diagnosis of
      heparin-induced thrombocytopenia.
AB  - Owing to the disadvantage of radioactivity of the carbon 14 serotonin release
      assay and the time-consuming procedure of the enzyme immunoassay, we developed a
      high-pressure liquid chromatography (HPLC) method to detect serotonin released
      from donor platelets in the presence of heparins and serum samples from patients
      with heparin-induced thrombocytopenia (HIT). Samples were analyzed from 60
      healthy control subjects, 19 patients with HIT, and 20 patients without HIT after
      incubation with heparin, low-molecular-weight heparin (LMWH), and danaparoid.
      Serotonin release was measured from platelets, 300 x 10(3)/microL, by HPLC.
      Serotonin eluted as a single peak from the HPLC column. Serum samples from
      patients with HIT released 5.5 to 352.5 and 6.6 to 1,533.3 ng/mL of serotonin
      from platelets in the presence of 0.2 IU/mL of heparin and LMWH, respectively. In
      the presence of 0 IU/mL of heparin, LMWH, danaparoid, and control samples, less
      than 2.5 ng/mL of serotonin were released. The HPLC method permits a rapid,
      sensitive, and quantitative determination of serotonin released from donor
      platelets for laboratory confirmation of HIT.

PMID- 12047142
TI  - High apoptotic activity and low epithelial cell proliferation with
      underexpression of p21(WAF1/CIP1) and p27Kip1 of mucinous carcinomas of the
      colorectum: comparison with well-differentiated type.
AB  - We comparatively assessed 41 mucinous colorectal carcinomas (MUCs) and 620 non
      MUC (well-, moderately, and poorly differentiated adenocarcinoma) cases for
      clinicopathologic findings; and 41 MUCs and 115 randomly selected non-MUCs also
      were studied for the following: (1) apoptotic activity and Ki-67
      immunoreactivity; (2) immunohistochemical expression of p21(WAF1/CIP1), p27Kip1,
      p53, and bcl-2; and (3) c-Ki-ras mutations. The rates for lymph node involvement
      and peritoneal dissemination were higher in MUCs than in non-MUCs. Multivariate
      analysis showed MUCs to have a worse prognosis than well-differentiated
      adenocarcinomas. The Ki-67 labeling for MUCs was significantly lower than that
      for non-MUCs, whereas the apoptotic index was significantly higher than for the
      well-differentiated type. The labeling for p21(WAF1/CIP1) and p27Kip1 was lower
      in MUCs (2.7% and 35.3%, respectively) than in well-differentiated
      adenocarcinomas (4.2% and 48.6%, respectively). MUCs can be considered a
      different tumor from the well-differentiated type, with a poor prognosis owing to
      frequent lymph node metastasis and peritoneal dissemination, and characterized by
      high apoptotic and low proliferative activities associated with low
      p21(WAF1/CIP1) and p27Kip1 expression.

PMID- 12047143
TI  - HER2/neu amplification in breast cancer: stratification by tumor type and grade.
AB  - The presence of HER2/neu gene amplification is prognostically and therapeutically
      significant for patients with breast cancer. We sought to determine whether a
      relationship exists between HER2/neu gene amplification and the histologic type
      and grade of tumor. The histologic features and corresponding HER2/neu
      amplification results of 401 cases of invasive breast carcinoma were reviewed.
      Lobular carcinomas were less likely than ductal carcinomas to have HER2/neu
      amplification. Amplification was less frequent in Scarff-Bloom-Richardson grade I
      ductal carcinomas than in grades 2 and 3. Metastatic carcinomas frequently
      displayed HER2/neu amplification (6/20 [30%]). Our results support a correlation
      between HER2/neu amplification and the histologic type and grade of breast
      cancer. We suggest reexamination of tumors diagnosed as Scarff-Bloom-Richardson
      grade I invasive ductal carcinomas or lobular carcinomas if the lesion displays
      HER2/neu amplification to assure the exclusion of a higher grade of lesion or of
      missed ductal components.

PMID- 12047144
TI  - Urinary cytology associated with human polyomavirus and indinavir therapy in HIV
      infected patients.
AB  - We retrospectively analyzed 155 urine cytology samples (78 from patients treated
      with indinavir; 77, no indinavir) from 90 HIV+ patients to evaluate possible
      association between human polyomavirus and hematuria and to describe indinavir
      associated urinary cytologic findings. The CD4 count also was recorded. Variables
      studied included the presence of cellular viral changes consistent with
      polyomavirus infection (PVCs), microscopic hematuria, multinucleated cells,
      indinavir crystals, neutrophils, and eosinophils. Twenty-two samples (15.8%) from
      patients with CD4 counts of more than 200/microL (>200 x 10(6)/L) showed PVCs.
      Multinucleated cells, of presumed histiocytic origin based on morphologic
      features and selective immunocytochemical findings, were present in a higher
      percentage of samples from indinavir-treated patients. Neutrophils were present
      in a higher percentage of indinavir-treated patients. Indinavir crystals were
      identified in 9 samples (12%) from patients receiving indinavir The lower
      percentage of PVCs in HIV+ patients with high CD4 counts likely represents an
      indirect antipolyomavirus indinavir effect by boosting immunity. Multinucleated
      cells (presumably histiocytic) and acute inflammation are associated with
      indinavir therapy. Indinavir crystals have a characteristic fan or circular
      lamellate appearance. Because indinavir crystals may be associated with
      genitourinary disease, recognizing and reporting them is clinically relevant in
      HIV+ patients.

PMID- 12047145
TI  - The influence of percentage of preradiation needle biopsies with adenocarcinoma
      and total radiation dose on the pathologic response of unfavorable prostate
      adenocarcinoma.
AB  - We studied relationships among clinicopathologic factors in 78 patients with
      unfavorable prostate adenocarcinoma treated in a dose-escalation radiation
      therapy (RT) study using pre- and 18-month protocol post-RT biopsy specimens. Pre
      RT factors analyzed were serum prostate-specific antigen (PSA) level, Gleason
      score, and percentage of needle cores with adenocarcinoma; post-RT factors were
      percentage of needle cores with adenocarcinoma and amount of radiation effect on
      the adenocarcinoma. Of 78 patients, 42 (54%) had residual adenocarcinoma in the
      post-RT biopsy specimen. Lower total RT dose and dose per implant and greater
      serum PSA level were associated with an increasing percentage of needle cores
      with residual post-RT adenocarcinoma. Lower RT dose, an increasing percentage of
      pre-RT needle cores with adenocarcinoma, and a greater serum PSA level were
      associated with an increasing percentage of post-RT needle cores with no to
      moderate RT effect scores in adenocarcinoma. The mean percentage of pre-RT and
      post-RT needle cores with adenocarcinoma was greater in patients with post-RT
      biopsy specimens with no to moderate RT effect. The percentage of pre-RT needle
      cores with adenocarcinoma (a surrogate marker of adenocarcinoma volume), serum
      PSA level, and RT dose are the key components in the dose-response relationship.
      Gleason score and gland volume did not contribute significantly to this
      relationship.

PMID- 12047146
TI  - HER2 assessment by immunohistochemical analysis and fluorescence in situ
      hybridization: comparison of HercepTest and PathVysion commercial assays.
AB  - We determined HER2 protein overexpression by immunohistochemical analysis and
      HER2 gene amplification by fluorescence in situ hybridization (FISH) in 215
      formalin-fixed, paraffin-embedded breast tumors. Pathologist concordance for
      immunohistochemical scoring, and HER2 status concordance, as determined by
      immunohistochemistry and FISH, were high for immunohistochemical 3+, 1+, and 0
      tumors but poor for 2+ tumors. Consensus immunohistochemical scores correlated
      with absolute and chromosome 17 (CEPI 7)-corrected HER2 gene copy number Among
      HER2-nonamplified tumors, the immunohistochemical score and mean absolute
      chromosome 17 (CEP17) copy number were weakly correlated. Seventeen tumors were
      HER2-amplified using absolute HER2 gene criteria but nonamplified when corrected
      for chromosome 17 polysomy (8 of these were immunohistochemical 2+). Assessment
      of benign epithelium within the immunohistochemical slides revealed either no
      staining or basolateral membrane staining, suggesting normal HER2 protein
      expression. Twenty tumors showing similar basolateral HER2 immunostaining were
      all low-moderate grade, tubule-forming, and HER2-nonamplified (17) or borderline
      amplified (3). Additional studies relating changes in HER2 gene content due to
      amplification or chromosome 17 polysomy and HER2 protein expression may be
      helpful to pathologists who interpret HER2 immnuohistochemical slides. Breast
      tumors scored at 2+ should be analyzed by FISH, preferably using a dual-probe
      FISH assay capable of distinguishing HER2 gene amplification from chromosome 17
      polysomy.

PMID- 12047147
TI  - Expression of cytokeratins 7 and 20 in ovarian neoplasia.
AB  - To further delineate specific staining patterns and refine the differential
      usefulness of cytokeratin (CK) 7/20 staining, we studied multiple ovarian tumors
      and primary nongynecologic neoplasms likely to metastasize to the ovary.
      Immunohistochemical analysis with semiquantitative grading to give quartile
      scores (0-4) was performed on 127 cases. Subsequent analysis indicated that a
      more informative diagnostic segregation could be achieved with a biphasic grading
      system (>50% staining, positive; 50% or less, negative). Lower intestinal tumors
      were CK7- and usually CK20+, while upper gastrointestinal tumors, including those
      of pancreatobiliary origin, were mostly CK7+ and CK20-. Serous papillary ovarian
      tumors were all CK7+ and CK20-. Mucinous ovarian carcinomas were all CK7+ and
      slightly more often CK20-, whereas the small number of ovarian borderline
      mucinous tumors studied were the most problematic, with no clear pattern.
      Multiple different tumor types from all nonovarian gynecologic sites were fairly
      consistently CK7+ and almost always CK20-. Differential CK staining of mucinous
      tumors of the female genital tract using CK7 and CK20 is useful for predicting
      the site of origin, provided samples are adequate in size. The most specific
      usefulness is the identification of lower gastrointestinal vs "other" neoplasms.

PMID- 12047148
TI  - Flow cytometric analysis of cerebrospinal fluid samples and its usefulness in
      routine clinical practice.
AB  - Low volume and few cells have hampered the use of flow cytometry for studying
      cerebrospinal fluid (CSF) in routine clinical practice, although information
      about the cellular phenotypes present in this type of sample is of great value in
      many diseases. We developed a novel flow cytometric strategy capable of
      identifying total CSF T lymphocytes and the CD4+ subset, even in CSF samples with
      as few as 1 leukocyte per 3 microL of sample. We also showed that identification
      of CD8+ T cells could be achieved in most samples, while B lymphocytes are
      detectable only in samples with more than 5 cells per microliter. These findings
      demonstrate the reliability of this method to improve the diagnostic accuracy of
      classic cytologic studies in many neurologic disorders.

PMID- 12047151
TI  - trans-RuH(eta1-BH4)(binap)(1,2-diamine): a catalyst for asymmetric hydrogenation
      of simple ketones under base-free conditions.
AB  - Reaction of a chiral RuCl2(diphosphine)(1,2-diamine) complex and NaBH4 forms
      trans-RuH(eta1-BH4)(diphosphine)(1,2-diamine) quantitatively. The TolBINAP/DPEN
      Ru complex has been characterized by single crystal X-ray analysis as well as NMR
      and IR spectra. The new Ru complexes allow for asymmetric hydrogenation of simple
      ketones in 2-propanol without an additional strong base. Various base-sensitive
      ketones are convertible to chiral alcohols in a high enantiomeric purity with a
      substrate/catalyst ratio of up to 100 000 under mild conditions.
      Configurationally unstable 2-isopropyl- and 2-methoxycyclohexanone can be
      kinetically resolved with a high enantiomer discrimination. This procedure
      overcomes the drawback of an earlier method using RuCl2(diphosphine)(diamine) and
      an alkaline base, which sometimes causes undesired reactions such as ester
      exchange, epoxy-ring opening, beta-elimination, and polymerization of ketonic
      substrates.

PMID- 12047149
TI  - Juxtaglomerular cell tumor.

PMID- 12047150
TI  - Solvent-induced aggregation through metal...metal/pi...pi interactions: large
      solvatochromism of luminescent organoplatinum(II) terpyridyl complexes.
AB  - A dramatic color change and tremendous emission enhancement have been "switched
      on" upon increasing diethyl ether ratio in acetonitrile or acetone solution of
      [Pt(tpy)(CC-CCH)]OTf, attributed to the formation of Pt...Pt and pi-pi
      interactions. Two crystal forms (dark-green and red) of [Pt(tpy)(CC-CCH)]OTf,
      together with [Pt(tBu3-tpy)(CC-CCH)]OTf, show different crystal-packing modes as
      revealed by X-ray crystallography.

PMID- 12047152
TI  - A new ruthenium-catalyzed hydrogen-transfer reaction: transformation of 3-benzyl
      but-1-ynyl ethers into 1,3-dienes and benzaldehyde.
AB  - We report a ruthenium-catalyzed reaction for various 3-benzyl but-1-ynyl ethers
      with suitable functionalities. Treatment of these substrates with
      TpRu(PPh3)(CH3CN)2PF6 (8.0 mol %) catalyst in 1,2-dichloroethane (80 degrees C,
      12 h) afforded functionalized 1,3-dienes and benzyl aldehyde in good yields. This
      process is considered to be a tandem dealkoxylation and transfer hydrogenation.
      Deuterium-labeling experiments reveal that the migration of different hydrogen
      atoms proceeds regiospecifically. A plausible mechanism is proposed on the basis
      of the results of isotope experiment.

PMID- 12047153
TI  - Stereoselectivity of the benzannulation reaction: efficient central-to-axial
      chirality transfer.
AB  - High diastereoselectivity is observed in the preparation of configurationally
      stable allocolchicinoids 5 from Fischer carbene complexes 4 and 1-pentyne. The
      analogous reaction of complexes 8 gives 9 with moderate diastereoselectivity for
      the opposite atropisomer and this selectivity can be taken to high levels under
      thermodynamic conditions.

PMID- 12047154
TI  - Cobalt-catalyzed Heck-type reaction of alkyl halides with styrenes.
AB  - A cobalt complex, CoCl2[1,6-bis(diphenylphosphino)hexane], catalyzes an
      alkylation reaction of styrenes in the presence of Me3SiCH2MgCl in ether to yield
      beta-alkylstyrenes. A variety of alkyl halides including alkyl chlorides can be
      employed as an alkyl source. A radical mechanism is strongly suggested for this
      alkylation reaction.

PMID- 12047155
TI  - First anionic micelle with unusually long lifetime: self-assembly of fluorocarbon
      hydrocarbon hybrid surfactant.
AB  - The exchange of a fluorocarbon-hydrocarbon hybrid surfactant between monomer and
      micelle states in deuterium oxide has been investigated through 19F NMR and 1H
      NMR experiments. The CF3 group in the surfactant gives two kinds of 19F NMR
      signals corresponding to the monomer and micelle states, indicating slow
      surfactant exchange on NMR time scale. The lifetime (taumic) of micelle,
      estimated by line shape analysis of the signals, is 2.0 ms at cmc, 102 to 103
      times longer than that of general surfactant micelles. Pulsed-gradient spin-echo
      (PGSE) experiments show that the hybrid surfactant forms considerably small
      micelles with a hydrodynamic radius of 0.6 nm. In contrast, at a higher
      concentration where no slow surfactant exchange is observed, the micelle radius
      increases to 1.1 nm. The interdigitation between the surfactant molecules in the
      micelle will contribute to the unusually long lifetime, in other words, slow
      surfactant exchange on the NMR time scale.

PMID- 12047156
TI  - Asymmetric synthesis of syn- and anti-1,3-amino alcohols.
AB  - The first application of metalloenamines derived from N-sulfinyl imines is
      reported for the highly diastereoselective addition to aldehydes. Reduction of
      the beta-hydroxy-N-sulfinyl imine products with catecholborane and LiBHEt3
      provides syn- and anti-1,3-amino alcohol derivatives, respectively, with very
      high diastereomeric ratios.

PMID- 12047157
TI  - Femtosecond excitation energy transport in triarylamine dendrimers.
AB  - The search for a model that can be used to describe the optical excitation
      migration in dendrimers has attracted great attention. In most cases in a
      dendrimer the conjugation is disrupted at the branching point; however, the
      excitation is delocalized. The strength of interactions among neighboring
      chromophores plays a key role in determining the energy migration mechanism.
      Conversely, having many identical chromophores held tightly together in an
      ordered macromolecular architecture will allow for many dipoles to be accessible
      for optical excitation. Therefore, the relative orientation of dipoles will be
      important in determining the mechanism of energy migration. Here we report the
      synthesis and photo-physical investigation of triarylamine-based dendrimers. Two
      important synthetic steps were utilized in the synthesis. First, we employed
      diphenylmethyl protective groups on the amines to assist in deprotective
      hydrogenolysis of the larger structures. Second, highly active catalysts for
      formation of both di- and triarylamines that are based on a 1:1 ratio of P(t-Bu)3
      and Pd(dba)2 improved reaction yields of the C-N bond formation and decreased
      reaction times The energy migration processes in the dendrimers were investigated
      utilizing ultrafast time-resolved fluorescence anisotropy measurements. The
      fluorescence anisotropy of all three dendrimers decayed to a residual value
      within approximately 100 fs. This fluorescence anisotropy decay showed a general
      trend in decreasing with increasing dendrimer generation. The residual anisotropy
      value also showed a gradual decrease with an increase in the dendrimer
      generation. This fast energy depolarization is discussed through a coherent
      excitonic mechanism among dipoles oriented in different directions. We believe
      that the formation of coherent domains leads to fast energy migration extending
      over a large part of the dendrimer.

PMID- 12047158
TI  - Structure and ion exchange properties of a new cobalt borate with a tunnel
      structure "templated" by Na+.
AB  - The new anhydrous borate Na2Co2B12O21 has been synthesized by flux methods and
      studied by single-crystal X-ray diffraction (space group I2/a with a =
      17.1447(15) A, b = 4.5530(5) A, c = 19.4408(15) A, beta = 103.212(5) degrees , V
      = 1477.4(2) A3, Z = 4). Refinement of its structure reveals it is the first
      metaborate exhibiting a tunnel network, with internal dimensions of 4.5 x 8.8 A2.
      Further single-crystal diffraction studies show that the Na+ ions within the
      tunnels are exchangeable with Li+ along with the absorption of water molecules to
      form Li2(H2O)2Co2B12O21, making this compound a unique non-siliceous zeotype.

PMID- 12047159
TI  - Diastereoselective silacyclopropanations of functionalized chiral alkenes.
AB  - Lithium reduction of di-tert-butyldichlorosilane and thermal silylene transfer
      (105-125 degrees C) are complementary methods for the highly diastereoselective
      silacyclopropanations of a range of functionalized chiral olefins to afford
      complex silacycles. We have shown that functionalized cyclohexenes,
      cyclopentenes, norbornenes, and 1,1-disubstituted alkenes undergo
      silacyclopropanation with excellent diastereoselectivity (92:8 to >99:1). Our
      results demonstrate that steric interactions, rather than oxygen-directing
      effects, control the approach of the silylene or silylenoid intermediate to the
      olefin. We believe that the sterically demanding nature of the di-tert
      butylsilylene species prevents coordination to the oxygen functionality. Thermal
      silylene transfer conditions exhibit broad functional group tolerance; the
      elevated temperatures for silylene transfer, however, cannot be employed for the
      silacyclopropanation of substituted cyclohexenes and 1,1-disubstituted alkenes.
      Elaboration of the resulting functionalized silacyclopropanes provides an
      efficient route to polyoxygenated products.

PMID- 12047160
TI  - Novel strategy for the design of a new zinc finger: creation of a zinc finger for
      the AT-rich sequence by alpha-helix substitution.
AB  - In this communication, a novel strategy for the design of a zinc finger peptide
      on the basis of alpha-helix substitution has been demonstrated. Sp1HM is a helix
      substituted mutant for the wild-type Sp1(zf123) and its alpha-helix of each
      finger is replaced by that of fingers 4-6 of CF2-II. The circular dichroism
      spectrum of Sp1HM suggests that Sp1HM has an ordered secondary structure similar
      to that of Sp1(zf123). From the analyses of the DNA binding affinity and
      specificity by gel mobility shift assay, it is clearly indicated that Sp1HM
      specifically binds to the AT-rich sequence (5'-GTA TAT ATA-3') with 3.2 nM
      dissociation constants. Moreover, the zinc finger peptides for the sequence
      alternating between the AT- and GC-rich subsites can also be created by the alpha
      helix substitution. This strategy is evidently effective and is also more
      convenient than the phage display method. Consequently, our design method is
      widely applicable to creating zinc finger peptides with novel binding
      specificities.

PMID- 12047161
TI  - Syntheses and skeletal transformations of NCNH- and NCN-bridged tetrairidium(III)
      cages.
AB  - The diiridium complex [Cp*IrCl2]2 (Cp* = eta5-C5Me5) reacts with 2 equiv of
      Na(NCNH) at room temperature to afford the 16-membered macrocyclic tetrairidium
      complex [Cp*IrCl(mu2-NCNH-N,N')]4 (1a). Treatment of 1a with 4 equiv of
      triethylamine at room temperature leads to the formation of the "C3-elongated
      cubane-like" tetrairidium complex [Cp*Ir(mu3-NCN-N,N,N')3(IrCp*)3(mu3-NCN-N,N,N)]
      (2) as the major product, which is further converted into the cubane-type complex
      [Cp*Ir(mu3-NCN-N,N,N)]4 (3) on refluxing in p-xylene. The molecular structures of
      [Cp*IrI(mu3-NCNH-N,N')]4.C7H8 (1b.C7H8), 2.0.5C7H8, and 3 have been determined by
      X-ray analyses.

PMID- 12047162
TI  - Helical self-assembly of substituted benzoic acids: influence of weaker X...X and
      C-H...X interactions.
AB  - The X-ray crystal packing analyses of the sterically encumbered halogen
      substituted benzene carboxylic acids 1-4 reveal a novel and unprecedented crystal
      packing in that the association of the carboxyl groups through O-H...O bonds
      results in the generation of a helix along the 41-screw axis. Such an
      organization of the acids is shown convincingly to be a result of the close
      packing, which exploits the weaker X...X and C-H...X interactions in conjunction
      with the stronger O-H...O hydrogen bonds. In contrast, the chloro- and bromo
      substituted durene carboxylic acids 6 and 7 exhibit a pattern that is akin to
      tape/ribbon involving the centrosymmetric-dimer motif and X...X short
      intermolecular interactions. The structural investigations demonstrate the
      ability of the weaker interactions in modifying the supposedly "robust"
      centrosymmetric-dimer motif of the carboxyl groups in a decisive manner.

PMID- 12047163
TI  - Stepwise cycloreversion of oxetane radical cations with initial C-O bond
      cleavage.
AB  - 2,4,6-Triaryl(thia)pyrylium salts have been used as electron-transfer
      photosensitizers for the cycloreversion of the oxetane ring system. The radical
      cation of 2,3-diphenyl-4-hydroxymethyloxetane (1) undergoes stepwise splitting
      via initial O-C2 cleavage. Spin and charge in the resulting intermediate are
      located in the oxygen and carbon atoms, respectively. Subsequent intramolecular
      nucleophilic attack produces 2,3-diphenyl-4-hydroxytetrahydrofuran (4a).
      Formation of this product occurs in the submicrosecond time scale, competing with
      C3-C4 cleavage to the detectable (lambdamax = 470 nm) trans-stilbene radical
      cation.

PMID- 12047164
TI  - Regiospecific synthesis of bicyclo- and heterobicyclo-gem-difluorocyclobutenes
      using functionalized fluoroallenes and a novel Mo-catalyzed intramolecular [2 +
      2] cycloaddition reaction.
AB  - The first synthesis of functionalized gem-difluoroallenes 4 served as platform
      for an unprecedented molybdenum-catalyzed intramolecular allene-alkyne [2 + 2]
      cycloaddition that produced 6, a hitherto unknown class of bicyclo- and
      heterobicyclo-CF2-containing cyclobutenes.

PMID- 12047165
TI  - A general catalytic allylation using allyltrimethoxysilane.
AB  - A general and mild catalytic allylation of carbonyl compounds, applicable to
      aldehydes, ketones, and imines is developed using allyltrimethoxysilane as the
      allylating reagent. The reaction proceeds smoothly with 1-10 mol % of CuCl and
      TBAT in THF at ambient temperature. Mechanism studies indicated that the copper
      alkoxide, allylfluorodimethoxysilane, and allyltrimethoxysilane are essential to
      promote the reaction efficiently. Preliminary extension of the reaction to the
      first catalytic enantioselective allylation of ketones using an allylsilane
      produced the product with 61% ee from acetophenone, using a CuCl-p-tol-BINAP-TBAT
      catalyst (15 mol %).

PMID- 12047166
TI  - Stereoselective synthesis of trifluoromethylated vicinal ethylenediamines with
      alpha-amino N-tert-butanesulfinimines and TMSCF3.
AB  - Isolable alpha-amino N-tert-butanesulfinimines were prepared through the
      condensation of Reetz's alpha-amino aldehydes (prepared from alpha-amino acids)
      with Ellman's (R)-N-tert-butanesufinamide without any racemization, and these
      were trifluoromethylated with TMSCF3 and TMAF (tetramethylammonium fluoride) to
      the corresponding vicinal ethylenediamines derivatives. Imines derived from l
      amino acids gave exclusively one diastereomer with a very high yield.

PMID- 12047167
TI  - On the electronic character of localized singlet 2,2-dimethoxycyclopentane-1,3
      diyl diradicals: substituent effects on the lifetime.
AB  - Photodenitrogenation of the diazenes 4 affords exclusively the housanes 5 through
      intramolecular cyclization of the spectrally detected and characterized singlet
      diradicals 3. The lifetime of singlet diradical 3, determined by transient
      absorption measurements, depends on the Y and Z substituents at the para position
      of the phenyl ring and has the following order: Y, Z = OMe, OMe > OMe, CN > CN,
      CN > OMe, H > Cl, Cl approximately CN, H approximately Me, Me > H, H. This
      unprecedented substituent effect reveals stabilization of the singlet 2,2
      dimethoxycyclopentane-1,3-diyl diradicals 3 through radical, zwitterionic, pi
      bonding, and hyperconjugative structures.

PMID- 12047168
TI  - Concerning the antileukemic agent jatrophatrione: the first total synthesis of a
      [5.9.5] tricyclic diterpene.
AB  - The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione
      (1) has been synthesized. The route begins with the tandem anionic oxy-Cope
      rearrangement/methylation/transannular ene cyclization of 5 and subsequent
      introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction
      of this functionality in 6 with LiAlH4/CuI/HMPA/THF sets the stage for the
      implementation of a Grob fragmentation and rapid generation of 8.
      Stereocontrolled intramolecular hydrosilylation allows for the subsequent
      introduction of a cyclic carbonate as in 11. This intermediate undergoes a
      remarkably smooth Treibs reaction to generate 12, thus serving as a pivotal step
      for making 1 available five steps later.

PMID- 12047169
TI  - Identification of asm19 as an acyltransferase attaching the biologically
      essential ester side chain of ansamitocins using N-desmethyl-4,5
      desepoxymaytansinol, not maytansinol, as its substrate.
AB  - The potent antitumor activity of the ansamitocins, polyketides isolated from
      Actinosynnema pretiosum, is absolutely dependent on a short acyl group esterified
      to the C-3 oxygen of the macrolactam ring. Asm19, a gene in the ansamitocin
      biosynthetic gene cluster with homology to macrolide O-acyltransferase genes, is
      thought to encode the enzyme catalyzing this esterification. A mutant carrying an
      inactivated asm19 no longer produced ansamitocins but accumulated N-desmethyl-4,5
      desepoxymaytansinol, rather than maytansinol, indicating that the acylation is
      not the terminal step of the biosynthetic sequence. Bioconversion experiments and
      in vitro studies with recombinant Asm19, expressed in Escherichia coli, showed
      that the enzyme is very specific toward its alcohol substrate, converting N
      desmethyl-4,5-desepoxymaytansinol (but not maytansinol) into ansamitocins, but
      rather promiscuous toward its acyl substrate, utilizing acetyl-, propionyl-,
      butyryl-, isobutyryl-, as well as isovaleryl-CoA.

PMID- 12047170
TI  - Gas-phase ion unimolecular dissociation for rapid phosphopeptide mapping by IRMPD
      in a Penning ion trap: an energetically favored process.
AB  - This communication discusses the efficient detection of the most important and
      common protein modification, phosphorylation, using ESI-FTICR-MS and IRMPD.
      Preliminary studies have demonstrated that within a complex protein digest, all
      phosphopeptides can be identified by a single IR laser irradiation event due to
      preferential dissociation of the modified peptides. This research demonstrates
      that the energy of activation for dissociation of the phosphopeptides is lower
      than that of the unmodified analogues providing the basis for the success of this
      technique. However, the P-O stretch (9.6-11 mum or 1042-909 cm-1) of this
      posttranslational modification is in direct resonance with the CO2 IR laser (10.6
      mum or 943 cm-1) used for IRMPD. Therefore, the vibrational frequency of the
      phosphate moiety may be an additional factor in the rapid first-order decay of
      phosphopeptides. Based upon the energetics of dissociation discussed in this
      manuscript, IRMPD of ions in a Penning ion trap is an ideal platform for rapid
      phosphopeptide mapping.

PMID- 12047171
TI  - Cation-recognized photosensitization in E-Z isomerization of 1,2-dichloroethylene
      by crowned benzophenones.
AB  - Photosensitized isomerization of 1,2-dichloroethylene with 15- and 18-membered
      ring crowned benzophenones (1a and 1b) as triplet sensitizers resulted in the
      cation-dependent increase in the Z/E isomer ratios up to ca. 10 by addition of
      alkali and alkaline earth metal ions in comparison with the metal-free reactions
      (Z/E = 1.5-2.1). The highest Z/E values were attained for 1a with Li+ (2.9) and
      Mg2+ (5.3), and for 1b with Na+ (8.2) and Ca2+ (9.8), respectively, among each
      family of alkali and alkaline earth metal ions. It was found that the cation
      recognized sensitization brought about the change of the inherent triplet energy
      ET as well as the PhiE/Phiz ratio to raise the Z/E isomer ratio of 1,2
      dichloroethylene.

PMID- 12047172
TI  - Preparation of helical transition-metal oxide tubes using organogelators as
      structure-directing agents.
AB  - We prepared novel transition-metal (Ti, Ta, V) oxide fibers with chiral, helical,
      and nanotubular structures. The nanostructured metal oxide materials were
      provided by the sol-gel polymerization of metal alkoxides using chiral self
      assemblies of organogelators as structure-directing agents. The chiral structures
      of the metal oxide fibers can be created by the formation of chiral self
      assemblies constructed by organogelators and the transcription of the organogel
      superstructure into metal oxides.

PMID- 12047173
TI  - Total synthesis of ecteinascidin 743.
AB  - The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor
      agent, has been accomplished. The synthesis features Ugi's 4CC reaction,
      intramolecular Heck reaction, phenol-aldehyde cyclization, and acid-induced
      intramolecular sulfide formation.

PMID- 12047174
TI  - Improvement and biological applications of fluorescent probes for zinc, ZnAFs.
AB  - The development and cellular applications of novel fluorescent probes for Zn2+,
      ZnAF-1F, and ZnAF-2F are described. Fluorescein is used as a fluorophore of
      ZnAFs, because its excitation and emission wavelengths are in the visible range,
      which minimizes cell damage and autofluorescence by excitation light. N,N-Bis(2
      pyridylmethyl)ethylenediamine, used as an acceptor for Zn2+, is attached directly
      to the benzoic acid moiety of fluorescein, resulting in very low quantum yields
      of 0.004 for ZnAF-1F and 0.006 for ZnAF-2F under physiological conditions (pH
      7.4) due to the photoinduced electron-transfer mechanism. Upon the addition of
      Zn2+, the fluorescence intensity is quickly increased up to 69-fold for ZnAF-1F
      and 60-fold for ZnAF-2F. Apparent dissociation constants (K(d)) are in the
      nanomolar range, which affords sufficient sensitivity for biological
      applications. ZnAFs do not fluoresce in the presence of other biologically
      important cations such as Ca2+ and Mg2+, and are insensitive to change of pH. The
      complexes with Zn2+ of previously developed ZnAFs, ZnAF-1, and ZnAF-2 decrease in
      fluorescence intensity below pH 7.0 owing to protonation of the phenolic hydroxyl
      group of fluorescein, whose pKa value is 6.2. On the other hand, the Zn2+
      complexes of ZnAF-1F and ZnAF-2F emit stable fluorescence around neutral and
      slightly acidic conditions because the pKa values are shifted to 4.9 by
      substitution of electron-withdrawing fluorine at the ortho position of the
      phenolic hydroxyl group. For application to living cells, the diacetyl derivative
      of ZnAF-2F, ZnAF-2F DA, was synthesized. ZnAF-2F DA can permeate through the cell
      membrane, and is hydrolyzed by esterase in the cytosol to yield ZnAF-2F, which is
      retained in the cells. Using ZnAF-2F DA, we could measure the changes of
      intracellular Zn2+ in cultured cells and hippocampal slices.

PMID- 12047175
TI  - Peptide loop-closure kinetics from microsecond molecular dynamics simulations in
      explicit solvent.
AB  - End-to-end contact formation rates of several peptides were recently measured by
      tryptophan triplet quenching (Lapidus et al. Proc. Natl. Acad. Sci. U.S.A. 2000,
      97, 7220). Motivated by these experiments, we study loop-closure kinetics for two
      peptides of different lengths, Cys-(Ala-Gly-Gln)n-Trp (n = 1, 2), in multiple all
      atom explicit-solvent molecular dynamics simulations with different initial
      conditions and force fields. In 150 simulations of approximately 20 ns each, we
      collect data covering 1.0 and 0.8 micros for the penta-peptide simulated with the
      AMBER and CHARMM force fields, respectively, and about 0.5 micros each with the
      two force fields for the octa-peptide. These extensive simulations allow us to
      analyze the dynamics of peptides in the unfolded state with atomic resolution,
      thus probing early events in protein folding, and to compare molecular dynamics
      simulations directly with experiment. The calculated lifetimes of the tryptophan
      triplet state are in the range of 50-100 ns, in agreement with experimental
      measurements. However, end-to-end contacts form more rapidly, with characteristic
      times less than 10 ns. The contact formation rates for the two force fields are
      similar despite differences in the respective ensembles of peptide conformations.

PMID- 12047176
TI  - Guest encapsulation and self-assembly of molecular capsules in polar solvents via
      multiple ionic interactions.
AB  - Herein we report the formation and characterization of a novel type of capsules
      resulting from the self-association between oppositely charged complementary
      building blocks in MeOH/H2O. The assembly is based on the interaction between
      tetraamidinium calix[4]arenes 1a-d and tetrasulfonato calix[4]arene 2. Evidence
      for the formation of the expected 1:1 assemblies is provided by proton NMR, ESI
      MS, and ITC. The association process is fast on the NMR time scale and strongly
      entropy driven, with association constants in the range of 10(6) M-1. The system
      1a.2 shows binding affinity toward acetylcholine, tetramethylammonium, and N
      methylquinuclidinium cations.

PMID- 12047177
TI  - Total synthesis of the anticancer natural product OSW-1.
AB  - The highly potent anticancer natural saponin OSW-1 has been successfully
      synthesized from commercially available 5-androsten-3beta-ol-17-one 79 in 10
      operations with 28% overall yield. The key steps in the total synthesis included
      a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation
      of 80 and a highly stereoselective 1,4-addition of alpha-alkoxy vinyl cuprates 68
      to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total
      synthesis demonstrated once again the versatile synthetic applications of alpha
      halo vinyl ether chemistry developed in our laboratories.

PMID- 12047178
TI  - Solid-phase synthesis and biochemical studies of O-boranophosphopeptides and O
      dithiophosphopeptides.
AB  - Signal transduction cascades maintain control over important cellular processes
      such as cell growth and differentiation by orchestrating protein phosphorylation
      and dephosphorylation. Specific control of these processes in vivo and in vitro
      can be achieved with peptide analogues that mimic the binding properties of
      phosphoproteins. We present here the solid-phase synthesis of two novel classes
      of phosphopeptide mimetics, O-boranophosphopeptides and O-dithiophosphopeptides,
      derivatized on tyrosine, serine, and threonine. The use of H-phosphonate and H
      phosphonothioate monoesters containing the base labile 9-fluorenemethyl
      protecting group was key to the synthesis of both phosphopeptide mimetics. O
      Boranophosphopeptides were synthesized by condensing O-(9-fluorenemethyl)-H
      phosphonate to the peptide hydroxylic component (tyr, ser, or thr) followed by
      oxidation with borane complexes. Similarly, the synthesis of O
      dithiophosphopeptides used the O-(9-fluorenemethyl)-H-phosphonothioate synthon
      and oxidation with elemental sulfur. Base elimination of the Fmol protecting
      group and cleavage from the solid support with concentrated ammonium hydroxide
      afforded the boranophosphopeptide and dithiophosphopeptide target compounds. Ac
      YIIPLPG-NH2, having either dithiophosphoryl tyrosine or boranophosphoryltyrosine
      but no sequence specificity for Yersinia protein tyrosine phosphatase (PTP), was
      found to competitively inhibit this enzyme with KI values of 430 +/- 50 and 670
      +/- 50 microM, respectively. In addition, both phosphopeptide analogues were
      resistant toward Yersinia PTP enzymatic hydrolysis. Under conditions (pH 8.0)
      where the phosphopeptide was rapidly dephosphorylated, the boranophosphopeptide
      hydrolyzed slowly (t1/2 = 15 h) and the dithiophosphopeptide was completely
      stable over 24 h.

PMID- 12047179
TI  - Estimating pKa values for pentaoxyphosphoranes.
AB  - pKa values are estimated independently, by two entirely different methods, for
      the ionizations of the apical and equatorial OH groups of two representative
      hydroxyphosphoranes. A bond length-pKa correlation based on crystal structures of
      cyclohexanol derivatives gives values of 13.5 +/- 1.5 and 8.62 +/- 1.87,
      respectively, for the apical and equatorial OH groups of
      tetracyclohexyloxyhydroxyphosphorane, and an ab initio molecular dynamics
      calculation gives values of 14.2 and 9.8 for the corresponding first ionizations
      of pentahydroxyphosphorane.

PMID- 12047180
TI  - Synthesis of poly(vinylene-arsine)s: alternating radical copolymerization of
      arsenic atomic biradical equivalent and phenylacetylene.
AB  - Novel organoarsenic polymers, poly(vinylene-arsine)s, were synthesized by a free
      radical alternating copolymerization of phenylacetylene with cyclooligoarsines as
      an atomic biradical equivalent. The polymerization between
      pentamethylpentacycloarsine (1a) or hexaphenylhexacycloarsine (1b) with
      phenylacetylene (2) in the presence of a catalytic amount of AIBN (in benzene;
      refluxing; for 12 h) gave the corresponding poly(vinylene-arsine)s. The obtained
      polymers were soluble in common organic solvents such as THF, chloroform, and
      benzene. From gel permeation chromatographic analysis (chloroform, PSt
      standards), the number-average molecular weights of the polymers from 1a and 1b
      were found to be 11500 and 3900, respectively. The structures of the polymers
      were supported by 1H and 13C NMR spectroscopies. The corresponding polymer was
      also obtained by irradiation of a benzene solution of 1a and 2 with xenon lamp at
      room temperature. After the polymer from 1a was stirred vigorously with 30% H2O2,
      the 1H NMR spectrum of the polymer showed the methyl proton that was assigned to
      As(III)-Me, suggesting the insensitivity of the trivalent state arsenic in the
      main chain to the oxidation. The structures and the molecular weights of the
      polymers were insensitive to the feed ratio of the monomers. This result
      indicates that the addition of the arsenic radical to phenylacetylene was a rate
      determining step in the copolymerization.

PMID- 12047181
TI  - Supramolecular fullerene-porphyrin chemistry. Fullerene complexation by metalated
      "jaws porphyrin" hosts.
AB  - Porphyrins and fullerenes are spontaneously attracted to each other. This new
      supramolecular recognition element is explored in discrete, soluble,
      coordinatively linked porphyrin and metalloporphyrin dimers. Jawlike clefts in
      these bis-porphyrins are effective hosts for fullerene guests. X-ray structures
      of the Cu complex with C60 and free-base complexes with C70 and a pyrrolidine
      derivatized C60 have been obtained. The electron-rich 6:6 ring-juncture bonds of
      C60 show unusually close approach to the porphyrin or metalloporphyrin plane.
      Binding constants in toluene solution increase in the order Fe(II) < Pd(II) <
      Zn(II) < Mn(II) < Co(II) < Cu(II) < 2H and span the range 490-5200 M-1.
      Unexpectedly, the free-base porphyrin binds C60 more strongly than the metalated
      porphyrins. This is ascribed to electrostatic forces, enhancing the largely van
      der Waals forces of the pi-pi interaction. The ordering with metals is ascribed
      to a subtle interplay of solvation and weak interaction forces. Conflicting
      opinions on the relative importance of van der Waals forces, charge transfer,
      electrostatic attraction, and coordinate bonding are addressed. The
      supramolecular design principles arising from these studies have potential
      applications in the preparation of photophysical devices, molecular magnets,
      molecular conductors, and porous metal-organic frameworks.

PMID- 12047182
TI  - Engineering the structure and magnetic properties of crystalline solids via the
      metal-directed self-assembly of a versatile molecular building unit.
AB  - We report the supramolecular chemistry of several metal complexes of N-(4
      pyridyl)benzamide (NPBA) with the general formula [Ma(NPBA)2AbSc], where M =
      Co2+, Ni2+, Zn2+, Mn2+, Cu2+, Ag+; A = NO3-, OAc-; S = MeOH, H2O; a = 0, 1, 2; b
      = 0, 1, 2, 4; and c = 0, 2. NPBA contains structural features that can engage in
      three modes of intermolecular interactions: (1) metal-ligand coordination, (2)
      hydrogen bonding, and (3) pi-pi stacking. NPBA forms one-dimensional (1-D) chains
      governed by hydrogen bonding, but when reacted with metal ions, it generates a
      wide variety of supramolecular scaffolds that control the arrangement of periodic
      nanostructures and form 1- (2-4), 2- (5), or 3-D (6-10) solid-state networks of
      hydrogen bonding and pi-pi stacking interactions in the crystal. Isostructural 7
      9 exhibit a 2-D hydrogen bonding network that promotes topotaxial growth of
      single crystals of their isostructural family and generates crystal composites
      with two (11) and three (12) different components. Furthermore, 7-9 can also form
      crystalline solid solutions (M,M')(NPBA)2(NO3)2(MeOH)2 (M, M' = Co2+, Ni2+, or
      Zn2+, 13-16), where mixtures of Co2+, Ni2+, and Zn2+ share the same crystal
      lattice in different proportions to allow the formation of materials with
      modulated magnetic moments. Finally, we report the effects that multidimensional
      noncovalent networks exert on the magnetic moments between 2 and 300 K of 1-D
      (4), 2-D (5), and 3-D (7, 8, 10, and 13-16) paramagnetic networks.

PMID- 12047183
TI  - The development of the first catalyzed reaction of ketenes and imines: catalytic,
      asymmetric synthesis of beta-lactams.
AB  - We report practical methodology for the catalytic, asymmetric synthesis of beta
      lactams resulting from the development of a catalyzed reaction of ketenes (or
      their derived zwitterionic enolates) and imines. The products of these asymmetric
      reactions can serve as precursors to a number of enzyme inhibitors and drug
      candidates as well as valuable synthetic intermediates. We present a detailed
      study of the mechanism of the beta-lactam forming reaction with proton sponge as
      the stoichiometric base, including kinetics and isotopic labeling studies.
      Stereochemical models based on molecular mechanics (MM) calculations are also
      presented to account for the observed stereoregular sense of induction in our
      reactions and to provide a guidepost for the design of other catalyst systems.

PMID- 12047185
TI  - Mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters
      catalyzed by BINAP-ruthenium(II) diacetate.
AB  - The mechanism of asymmetric hydrogenation of alpha-(acylamino)acrylic esters with
      Ru(CH(3)COO)(2)[(S)-binap] (BINAP = 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl),
      giving the S saturated products in >90% ee, has been investigated by means of a
      kinetic study, deuterium labeling experiments, isotope effect measurements, and
      NMR and X-ray analysis of certain Ru complexes. The hydrogenation in methanol
      under a low H2 pressure proceeds via a monohydride-unsaturate mechanism that
      involves the initial RuH formation followed by a reaction with an olefinic
      substrate. The migratory insertion in the enamide-RuH chelate complex occurs
      reversibly and endergonically in an exo manner, giving a five-membered
      metallacycle intermediate. The cleavage of the Ru-C bond is achieved with either
      H2 (major) or CH3OH (minor). Both of the pathways result in overall cis
      hydrogenation products. The hydrogen at C3 is mainly from an H2 molecule, and the
      C2 hydrogen is from another H2 or protic CH3OH. The major S and minor R
      enantiomers are produced via the same mechanism involving diastereomeric
      intermediates. The turnover rate is limited by the step of hydrogenolysis of a
      half-hydrogenated metallacyclic intermediate. The participation of two different
      hydrogen donor molecules is in contrast to the pairwise dihydrogenation using a
      single H2 molecule in the RhI-catalyzed reaction which occurs via a dihydride
      mechanism. In addition, the sense of asymmetric induction is opposite to that
      observed with S-BINAP-RhI catalysts. The origin of this phenomenon is interpreted
      in terms of stereocomplementary models of the enamide/metal chelate complexes. A
      series of model stoichiometric reactions mimicking the catalytic steps has
      indicated that most NMR-observable Ru complexes are not directly involved in the
      catalytic hydrogenation but are reservoirs of real catalytic complexes or even
      side products that retard the reaction.

PMID- 12047184
TI  - Is the corrolate macrocycle innocent or noninnocent? Magnetic susceptibility,
      Mossbauer, 1H NMR, and DFT investigations of chloro- and phenyliron corrolates.
AB  - In an attempt to determine the electron configuration of (anion)iron corrolates,
      i.e., whether they are S = 1 Fe(IV)-corrolate(3-) or S = 3/2 Fe(III)-corrolate(2
      *), with antiferromagnetic coupling between the iron and macrocycle electrons to
      yield overall S = 1, two axial ligand complexes of an iron octaalkylcorrolate
      have been studied by temperature-dependent magnetic susceptibility, magnetic
      Mossbauer, and 1H NMR spectroscopy, and the results have been compared to those
      determined on the basis of spin-unrestricted DFT calculations. Magnetic
      susceptibility measurements indicate the presence of a noninnocent macrocycle
      (corrolate (2-*)) for the chloroiron corrolate, with strong antiferromagnetic
      coupling to the S = 3/2 Fe(III) center, while those for the phenyliron corrolate
      are not conclusive as to the electron configuration. Temperature- and field
      dependent Mossbauer spectroscopic investigations of these two complexes yielded
      spectra that could be simulated with either electron configuration, except that
      the isomer shift of the phenyl-iron complex is -0.10 mm/s while that of the
      chloroiron complex is +0.21 mm/s, suggesting that the iron in the former is
      Fe(IV) while in the latter it is Fe(III). 1H NMR spectroscopic studies of both
      axial ligand complexes show large negative spin density at the meso carbons, with
      those of the chloroiron complex (Cai, S.; Walker, F. A.; Licoccia, S. Inorg.
      Chem. 2000, 39, 3466) being roughly four times larger than those of the
      phenyliron complex. The temperature dependence of the proton chemical shifts of
      the phenyliron complex is strictly linear. DFT calculations are consistent with
      the chloroiron complex being formulated as S1 = 3/2 Fe(III)-corrolate (2-*) S2 =
      1/2, with negative spin density at all nitrogens and meso carbons, and a net spin
      density of -0.79 on the corrolate ring and positive spin density (+0.17) on the
      chloride ion and +2.58 on the iron. In contrast, the phenyliron complex is best
      formulated as S = 1 Fe(IV)-corrolate (3-), but again with negative spin density
      at all nitrogens and meso carbons of the macrocycle, yet with the net spin
      density on the corrolate ring being virtually zero; the phenyl carbanion carbon
      has relatively large negative spin density of -0.15 and the iron +2.05. On the
      basis of all of the results, we conclude that in both the chloroiron and
      phenyliron complexes the corrolate ring is noninnocent, in the chloroiron complex
      to a much larger extent than in the phenyliron complex.

PMID- 12047186
TI  - Arresting butterfly-like intermediate nanocrystals of beta-Co(OH)2 via
      ethylenediamine-mediated synthesis.
AB  - A synthesis of beta-Co(OH)2 nanocrystalline materials has been investigated with
      the assistance of chelating agent ethylenediamine. By controlling precipitation
      processes, various forms of beta-Co(OH)2 crystallites can be prepared at
      different stages. The crystallite morphologies include two-dimensional hexagonal
      sheet platelets, one-dimensional nanorods, and butterfly-like nanocrystallite
      intermediates. In particular, a triangular construction unit for beta-Co(OH)2
      crystallites has been revealed with the ethylenediamine mediation in the
      synthesis. With the successful arrest of these butterfly-like intermediate
      crystallites, especially of linearly aligned "butterflies", the formation
      mechanism of one-dimensional nanorods or nanoribbons has been experimentally
      explained. The chemical composition of solution precursors and resultant beta
      Co(OH)2 crystallites has been analyzed with UV-vis/FTIR/CHN /XRD/TGA/TEM/SAED
      methods. The relationships among various observed crystallite morphologies have
      also been discussed on the basis of the experimental findings.

PMID- 12047187
TI  - Comprehensive study of the methyl effect on the solvolysis rates of bridgehead
      derivatives.
AB  - The effect of a bridgehead methyl group on the hydride ion affinity in the gas
      phase of bicyclo[1.1.1]pent-1-yl (1+), 1-norbornyl (3+), cubyl (5+), 1-adamantyl
      (7+), bicyclo[2.2.2]oct-1-yl (9+),and bicyclo[3.1.1]hept-1-yl (11+) cations has
      been studied using density functional theory and ab initio methods. It is
      concluded that the methyl group always increases the stability of the substituted
      cations. The effect of the solvent on the stability of methyl-substituted cations
      in relation to the unsubstituted cations has been studied using the polarizable
      continuum model of the self-consistent reaction field theory. In the case of
      rearranging cations, the nucleophilic assistance of the solvent is determined by
      means of the interaction energy of the corresponding water complexes. It is
      concluded that the solvent causes the relative stabilization of the parent
      cations. As a consequence, most of the methyl-substituted bridgehead derivatives
      show a lower solvolysis rate than the corresponding unsubstituted compounds. A
      nonqualitative explanation of the methyl effect on the relative stability of
      bridgehead cations in both gas phase and solution is given for the first time.
      The ratios of solvolysis products in the case of rearranging bridgehead cations
      have also been computed from the relative stability of the intermediate water
      complexes.

PMID- 12047189
TI  - Predictive concept for lone-pair distortions - DFT and vibronic model studies of
      AXn-(n-3) molecules and complexes (A = NIII to BiIII; X = F-I to I-I; n = 3-6).
AB  - The stereochemical and energetic consequences of the lone-pair effect in the
      title molecules and complexes have been studied by DFT calculations based on a
      vibronic coupling concept. The anionic complexes were examined as bare entities
      and, more realistically, in a polarizable charge-compensating solvent continuum.
      The tendency for distortions of AX3 compounds away from the high-symmetry parent
      geometry becomes more pronounced the larger the chemical hardness of a molecule
      and its constituents is; on the other hand, anionic complexes AXn-(n-3) (n = 4-6)
      become softer and less susceptible to distortion as compared to the corresponding
      AX3 molecule, the larger the coordination number and the anionic charge are.
      Thus, while all AX(3) compounds adopt the distorted C3v structure, only very few
      AX6(3-) species are calculated to deviate from the parent Oh geometry. If a
      complex possesses a low stabilization energy due to an unfavorable central
      ion/ligand size ratio, vibronic coupling may even lead to complete dissociation
      of one (SbF6(3-) --> SbF5(2-) + F-) or more (PF6(3-) --> PF4- + 2F-) ligands. The
      derived hardness rule perfectly covers the reported structural findings. The
      calculations indicate that the lone-pair effect is an orbital overlap phenomenon.
      The interpair repulsion within the valence shell, keeping the average bond
      distances constant, does not stabilize the distorted with respect to the parent
      geometry, in disagreement with the VSEPR model.

PMID- 12047188
TI  - Photoinduced charge-transfer dehydrogenation in a gas-phase metal-DNA base
      complex: Al-cytosine.
AB  - An Al-cytosine association complex has been generated via laser ablation of a
      mixture of aluminum and cytosine powders that were pressed into a rod form. The
      ionization energy of the complex is found to be 5.16 +/- 0.01 eV. The
      photoionization efficiency spectrum of Al-cytosine has also been collected. DFT
      calculations indicate that binding of Al to cytosine manifests a significant
      weakening of the N-H bond, predicted to have a strength of 1.5 eV in the complex,
      and a significant stabilization of the oxo tautomeric form relative to the
      hydroxy forms. The predicted ionization energy of 5.2 eV agrees well with the
      experimental value. The threshold for dehydrogenation/ionization of Al-cytosine,
      forming (Al-cytosine-H)+, is found to occur at photoexcitation energies between
      11.4 and 12.8 eV. This is a two-photon process that is proposed to occur via
      photoinduced electron transfer from Al to an antibonding (sigma) orbital
      localized on N-H. In the context of this mechanism, this work constitutes the
      first time charge transfer between a metal and DNA base has been photoinitiated
      in the gas phase.

PMID- 12047190
TI  - Conformational dynamics of tetraisopropylmethane and of tetracyclopropylmethane.
AB  - Tetraisopropylmethane (1) exists in solution as a mixture of two types of
      conformers (D2d and S4 time-averaged symmetry) in the ratio 93:7 at -110 degrees
      C, interconverting with a barrier of 9.7 kcal mol-1. Molecular mechanics
      calculations and the multiplicity of NMR signals at low temperature allow the
      assignment of these conformations. The only conformation populated in
      tetracyclopropylmethane (2) is the same type as the minor conformation (S4 time
      averaged symmetry) populated in 1. 13C NMR spectra at about -180 degrees C show
      that degenerate versions of this conformation interconvert with a barrier of 4.5
      kcal mol-1. Molecular mechanics calculations that characterize the six possible
      conformational types for these molecules, and the most important interconversion
      pathways, are reported. Calculated and experimental barriers match satisfactorily
      well.

PMID- 12047192
TI  - Experimental and theoretical studies of the products of laser-ablated thorium
      atom reactions with H2O in excess argon.
AB  - Reactions of laser-ablated Th atoms with H2O during condensation in excess argon
      have formed a variety of intriguing new Th, H, O species. Infrared absorptions at
      1406.0 and 842.6 cm-1 are assigned to the H-Th and Th=O stretching vibrations of
      HThO. Absorptions at 1397.2, 1352.4, and 822.8 cm-1 are assigned to symmetric H
      Th-H, antisymmetric H-Th-H, and Th=O stretching vibrations of the major primary
      reaction product H2ThO. Thorium monoxide (ThO) produced in the reaction inserts
      into H2O to form HThO(OH), which absorbs at 1341.0, 804.0, and 542.6 cm-1. Both
      HThO(OH) and ThO2 add another H2O molecule to give HTh(OH)3 and OTh(OH)2,
      respectively. Weaker thorium hydride (ThH1(-4)) absorptions were also observed.
      Relativistic DFT and ab initio calculations were performed on all proposed
      molecules and other possible isomers. The good agreement between experimental and
      calculated vibrational frequencies, relative absorption intensities, and isotopic
      shifts provides support for these first identifications of Th, H, O molecular
      species.

PMID- 12047191
TI  - An approach based on quantum chemistry calculations and structural analysis of a
      [2Fe-2S] ferredoxin that reveal a redox-linked switch in the electron-transfer
      process to the Fd-NADP+ reductase.
AB  - [2Fe-2S] ferredoxins act as electron carriers in photosynthesis by mediating the
      transfer of electrons from photosystem I to various enzymes such as
      ferredoxin:NADP(+):reductase (FNR). We have analyzed by density functional theory
      the possible variations of the electronic properties of the [2Fe-2S] ferredoxin,
      from the cyanobacterium Anabaena, depending on the redox-linked structural
      changes observed by X-ray diffraction at atomic resolution (Morales, R.; et al.
      Biochemistry 1999, 38, 15764-15773). The present results point out a specific and
      concerted role of Ser47, Phe65, and Glu94 located at the molecule surface, close
      to the iron-sulfur cluster. These residues were already known to be crucial for
      efficient electron transfer to FNR (e.g., Hurley, J. K.; et al. Biochemistry
      1997, 36, 11100-11117). Our calculations suggest that the Glu94 carboxylate
      negative charge regulates the electron charge delocalization between the Ser47 CO
      group and the Phe65 aromatic ring, depending on the redox state. The Glu94
      carboxylate is stabilized by a strong hydrogen bond implicating a hydroxyl
      containing side chain (i.e., Ser or Thr) at location 47. We propose that the
      Phe65 ring acts as an intermediary carrier receiving the reducing electron prior
      to its transfer from the reduced Fd to FNR, in view of its central role in the Fd
      FNR interaction.

PMID- 12047193
TI  - Solvent triggering between conformational states in amphiphilic shape-persistent
      macrocycles.
AB  - The amphiphilic shape-persistent macrocycle 1 containing four phenol-OH groups as
      polar side groups and four hexyloxy groups as nonpolar side groups in an
      adaptable arrangement was recrystallized from solvents of different polarity. X
      ray crystallography reveals that the conformation of the macrocycle is solvent
      dependent such that in the pyridine solvate only two of the nonpolar side groups
      point outward while in the THF solvate all four of them point outward. Moreover,
      in the latter case the three-dimensional packing leads to the formation of a
      supramolecular channel structure with a large pore size.

PMID- 12047194
TI  - Electric susceptibility of unsolvated glycine-based peptides.
AB  - The DC electric susceptibilities of unsolvated glycine-based peptides, WGn (W =
      tryptophan and G = glycine) with n = 1-5, have been measured by deflection of a
      molecular beam in an electric field. These are the first electric deflection
      measurements performed on peptides. At 300 K the susceptibilities are in the
      range of 200-400 A(3). By far the largest contribution to the susceptibilities is
      from the permanent dipole moment of the peptides. The results indicate that the
      peptides do not have rigid conformations with fixed dipoles. Instead the dipole
      is averaged as the peptides explore their energy landscape. For a given WGn
      peptide, all molecules have almost the same average dipole, which suggests that
      they all explore a similar energy landscape on the microsecond time scale of the
      measurement. The measured susceptibilities are in good overall agreement with
      values calculated from the average dipole moment deduced from Monte Carlo
      simulations.

PMID- 12047195
TI  - In search of covalently bound tetra- and penta-oxygen species: a photoelectron
      spectroscopic and Ab initio investigation of MO4- and MO5- (M = Li, Na, K, Cs).
AB  - Although neutral and ionic O4(0/-/+) species have been observed experimentally
      and considered for energetic materials, O4(2-) and O5(2-) dianions have not yet
      been explored. O4(2-) is valent isoelectronic to the well-known ClO3- and SO3(2-)
      anions, and O5(2-) is valent isoelectronic to ClO4- and SO4(2-). All are stable,
      common anions in solutions and inorganic salts. In this article, we explore the
      possibility of making covalently bound O4(2-) and O5(2-) species stabilized in
      the forms of M+O4(2-) and M+O5(2-) (M = Li, Na, K, Cs) in the gas phase. Laser
      vaporization experiments using M-containing targets and an O2-seeded carrier gas
      yielded very intense mass peaks corresponding to MO4- and MO5-. To elucidate the
      structure and bonding of the newly observed MO4- and MO5- species, we measured
      their photoelectron spectra and then compared them with ab initio calculations
      and the spectra of ClO3-, Na+SO3(2-), ClO4-, and Na+SO4(2-). Careful analyses of
      the experimental and ab initio results showed, however, that the observed species
      are of the forms, O2-M+O2- and O2-M+O3-. The more interesting M+O4(2-) and M+O5(2
      ) species were found to be higher-energy isomers, but they are true minima on the
      potential energy surfaces, which suggests that it might be possible to synthesize
      bulk materials containing covalently bound tetra- and pentatomic oxygen building
      blocks.

PMID- 12047196
TI  - Resonance Raman evidence for protein-induced out-of-plane distortion of the heme
      prosthetic group of mammalian lactoperoxidase.
AB  - Resonance Raman spectra have been acquired for resting state mammalian
      lactoperoxidase, LPO(N), and its six-coordinate, low-spin (6CLS) cyanide complex,
      LPO(CN), as well as for various heme l containing fragments resulting from
      partial or complete proteolytic digestion. These proteolytic fragments provide a
      useful set of reference compounds for analysis of the LPO(N) and LPO(CN) enzymes,
      using various ligands to generate well-defined five-coordinate and six-coordinate
      high-spin (5CHS and 6CHS) species. In addition, these model compounds, which
      contain zero, one, or two covalently attached ester linkages to polypeptide
      chains, are quite useful for determining the extent to which the presence of the
      ester linkages at the heme periphery affects the characteristic heme resonance
      Raman marker bands. The spectral results not only provide strong evidence for the
      formulation of the resting state enzyme as a 6CHS species, but also confirm the
      previously documented anomalous intensities of several low-frequency resonance
      Raman bands, which are most reasonably interpreted to arise from a protein
      induced out-of-plane distortion of the heme l macrocycle mediated by the covalent
      ester linkages to the associated polypeptide residues of the intact protein.

PMID- 12047198
TI  - Large-scale resonance amplification of optical sensing of volatile compounds with
      chemoresponsive visible-region diffraction gratings.
AB  - Micropatterning of the vapochromic charge-transfer salt,
      [Pt(CNC6H4C10H21)4][Pd(CN)4], on transparent platforms yields transmissive
      chemoresponsive diffraction gratings. Exposure of the gratings to volatile
      organic compounds (VOCs) such as chloroform and methanol leads to VOC uptake by
      the porous material comprising the grating lattice or framework, and a change in
      the material's complex refractive index, n. The index change is accompanied by a
      change in the degree of index contrast between the lattice and the surrounding
      medium (in this case, air), and a change in the diffraction efficiency of the
      grating. When a monochromatic light source that is not absorbed by the lattice
      material is employed as a probe beam, only changes in the real component of n are
      sensed. Under these conditions, the grating behaves as a nonselective, but
      moderately sensitive, sensor for those VOCs capable of permeating the porous
      lattice material. When a probe color is shifted to a wavelength coincident with
      the vapochromic charge-transfer transition of the lattice material, the sensor
      response is selectively amplified by up to 3.5 orders of magnitude, resulting in
      greatly enhanced sensitivity and some degree of chemical specificity. On the
      basis of studies at four probe wavelengths, the amplification effect is dominated
      by resonant changes in the imaginary component of the refractive index. The
      observed wavelength- and analyte-dependent amplification effects are
      quantitatively well described by a model that combines a Kramers-Kronig analysis
      with an effective-medium treatment of dielectric effects.

PMID- 12047197
TI  - Factors governing the protonation state of cysteines in proteins: an Ab
      initio/CDM study.
AB  - The detailed mechanism of metal-cysteine binding is still poorly understood. It
      is not clear if every metal cation can induce cysteine deprotonation, how the
      dielectric medium affects this process, and the extent to which other ligands
      from the metal's first and second coordination shell influence cysteine
      ionization. It is also not clear if the zinc cation, with its positive charge
      reduced by charge transfer from the first two bound cysteinates, could still
      assist deprotonation of the next one or two cysteines in Cys3His and Cys4 zinc
      finger cores. Here, we elucidate the factors governing the cysteine protonation
      state in metal-binding sites, in particular in Zn.Cys4 complexes, using a
      combined ab initio and continuum dielectric approach. Transition metal dications
      such as Zn2+ and Cu2+ and trivalent cations such as Al3+ with pronounced ability
      to accept charge from negatively charged Cys- are predicted to induce cysteine
      deprotonation, but not "hard" divalent cations such as Mg2+. A high dielectric
      medium was found to favor cysteine deprotonation, while a low one favored the
      protonated state. Polarizable ligands in the metal's first shell that can
      competitively donate charge to the metal cation were found to lower the
      efficiency of the metal-assisted cysteine deprotonation. The calculations predict
      that the zinc cation could assist deprotonation of all the cysteines during the
      folding of Cys4 zinc-finger cores and the [Zn.(Cys-)4]2- state is likely to be
      preserved in the final folded conformation of the protein provided the binding
      site is tightly encapsulated by backbone peptide groups or lysine/arginine side
      chains, which stabilize the ionized cysteine core.

PMID- 12047199
TI  - Interpreting molecular crystal disorder in plumbocene, Pb(C5H5)2: insight from
      theory.
AB  - Plane-wave density functional theory has been applied in a novel way to help
      interpret the molecular crystal structure disorder observed in the orthorhombic
      zigzag phase of plumbocene, Pb(C5H5)2. A crystal lattice comprising uniformly
      staggered C5H5 rings was found to be lower in energy by 2.8 kJ mol-1 per unit
      cell, compared to a uniformly eclipsed packing arrangement. This energy
      difference has been attributed to the difference in the strength of
      intermolecular interactions between the Pb(C5H5)2 chains for the two different
      lattices. The calculations performed allowed the determination of the
      crystallographic occupancy factors by a quantum mechanical technique for the
      first time.

PMID- 12047200
TI  - Do aurophilic interactions compete against hydrogen bonds? Experimental evidence
      and rationalization based on ab initio calculations.
AB  - [M(C6F5)(N(H)=CPh2)] (M = Ag (1) and Au (2)) complexes have been synthesized and
      characterized by X-ray diffraction analysis. Complex 1 shows a ladder-type
      structure in which two [Ag(C6F5)(N(H)=CPh2)] units are linked by a Ag(I)-Ag(I)
      interaction in an antiparallel disposition. The dimeric units are associated
      through hydrogen bonds of the type N-H...F(ortho). On the other hand, gold(I)
      complex 2 displays discrete dimers also in an antiparallel conformation in which
      both Au(I)-Au(I) interactions and N-H.F(ortho) hydrogen bonds appear within the
      dimeric units. The features of these coexisting interactions have been
      theoretically studied by ab initio calculations based on four different model
      systems in order to analyze them separately. The interactions have been analyzed
      at HF and MP2 levels of theory showing that, in this case, even at larger
      distances. The Au(I)-Au(I) interaction is stronger than Ag(I)-Ag(I) and that N
      H.F hydrogen bonding and Au(I)-Au(I) contacts have a similar strength in the same
      molecule, which permits a competition between these two structural motifs giving
      rise to different structural arrangements.

PMID- 12047201
TI  - Water rotational relaxation and diffusion in hydrated lysozyme.
AB  - This paper is concerned with the dynamics of water around a small globular
      protein. Dipolar second-rank relaxation time and diffusion properties of surface
      water were computed by extensive molecular dynamics simulations of lysozyme in
      water which lasted a total of 28 ns. Our results indicate that the rotational
      relaxation of water in the vicinity of lysozyme is 3-7 times slower than that in
      the bulk depending on how the hydration shell is defined in the calculation. We
      have also verified that the dynamics of water translational diffusion in the
      vicinity of lysozyme have retardations similar to rotational relaxation. This is
      a common assumption in nuclear magnetic relaxation dispersion (NMRD) studies to
      derive residence times. In contrast to bulk water dynamics, surface water is in a
      dispersive diffusion regime or subdiffusion. Very good agreement of dipolar
      second-rank relaxation time with NMRD estimates is obtained by using appropriate
      dimensions of the hydration shell. Although our computed second-rank dipolar
      retardations are independent of the water model, SPC/E describes more
      realistically the time scale of the water dynamics around lysozyme than does
      TIP3P.

PMID- 12047204
TI  - More than skin deep.

PMID- 12047205
TI  - Are bed exercises necessary following hip arthroplasty?
AB  - This study investigated whether a program of bed exercises increased the
      effectiveness of a mobility regimen during the acute period of hospitalisation,
      for patients who had undergone primary hip arthroplasty. Forty-two patients were
      randomly allocated, using a concealed allocation procedure, to one of two groups.
      Patients in the control group were mobilised according to a standard post
      operative protocol. Patients in the exercise group were also mobilised using this
      protocol but in addition received a program of bed exercises. Severity of pain,
      range of active hip flexion and hip abduction, and a functional assessment were
      measured by a blinded assessor on the third or fourth post-operative day and
      again on the seventh or eighth post-operative day. Significant improvements were
      found in all outcome measures from the third or fourth post-operative day to the
      seventh or eighth post-operative day. No significant differences were seen
      between groups for any outcome measures at either measurement time. Bed exercises
      do not appear to be of additional benefit to a mobility regimen during the period
      of acute hospitalisation after primary hip arthroplasty.

PMID- 12047206
TI  - Non-steroidal anti-inflammatory drugs (NSAIDs): physiotherapists' use, knowledge
      and attitudes.
AB  - This paper reports on a survey regarding physiotherapists' knowledge, use and
      attitudes to non-steroidal anti-inflammatory drugs (NSAIDs), some of which have
      recently been re-scheduled to non-prescription dispensing. A written survey
      instrument was developed and administered to 750 physiotherapists in South
      Australia, Tasmania and the Australian Capital Territory (50% of the registered
      physiotherapists). Responses were received from 285 physiotherapists. The survey
      identified opportunities for patient misuse and misadventures with NSAIDs in
      conjunction with physiotherapy management. Differences in physiotherapist
      understanding of the dosage and actions of oral and topic administrations of
      NSAIDs were highlighted, as were the moral and ethical responsibilities of
      physiotherapists to patients considering taking NSAIDs. The study identified the
      need for regular professional updates on quality use of NSAIDs.

PMID- 12047207
TI  - The effect of body position on maximal expiratory pressure and flow.
AB  - Positioning combined with coughing and huffing is frequently used to promote
      secretion clearance. Maximum expiratory pressure (MEP) and peak expiratory flow
      rate (PEFR) have been used as surrogate measures of cough and huff strength. This
      study investigated the effect of body position on MEP and PEFR. Repeated measures
      of MEP and PEFR were performed across seven randomised positions (standing, chair
      sitting, sitting in bed with backrest vertical, sitting in bed with backrest at
      45 degrees, supine, side lying, and side lying with head down tilt 20 degrees) on
      25 adults with normal respiratory function (NRF) and 11 adults with chronic
      airflow limitation (CAL). For the NRF group, MEP in standing (143+/-10cmH2O,
      mean+/-SEM) was significantly higher than MEP in chair sitting (133+/-10cmH2O)
      which in turn was significantly higher than in the remaining positions. The MEP
      in head down tilt (108+/-9cmH2O) was significantly lower than in all other
      positions. The PEFR in standing (571+/-24L/min) was significantly higher and head
      down tilt (486+/-23L/min) was significantly lower than in all other positions.
      For the CAL group, MEP in standing (134+/-18cmH2O) was significantly higher,
      while in head down tilt (96+/-15cmH2O) was significantly lower, than in most
      other positions. For the CAL group, PEFR in standing (284+/-40ml/sec) was
      significantly higher, while in head down tilt (219+/-38ml/sec) was significantly
      lower, than in most other positions. Body position has a significant effect on
      MEP and PEFR in NRF and CAL subjects, with the lowest values in the head down
      position. Thus, to maximise the strength of expiratory manoeuvres during
      treatments that use the head down position, patients should be encouraged to
      adopt a more upright position when coughing or huffing.

PMID- 12047208
TI  - Professional issues for physiotherapists in family-centred and community-based
      settings.
AB  - This paper reports results from a qualitative study of physiotherapists in a
      community-based and family-centred setting in which a growing awareness of the
      family-centred approach accompanied the transition from an institutional
      structure to a predominantly community-based structure. The goal was to gain
      insight into how a family-centred philosophy was working and to explore the
      benefits and dilemmas for physiotherapists in such a setting. Semi-structured
      interviews were conducted with 10 physiotherapists working with children with
      disabilities. Analysis of the results against a continuum of family control
      versus physiotherapist control showed that physiotherapists saw their roles as
      working with the family to discuss shared goals. However, qualitative analyses
      showed tensions between the policy of family involvement and another influential
      policy in physiotherapy: evidence-based practice. Further, there were tensions if
      the desires of the family could not be matched with available resources. The
      results show benefits and barriers to working in a community-based, family
      centred approach. Barriers included practical dilemmas, policy dilemmas, and
      career dilemmas. This paper argues that, while family-centred practice is
      supported by the literature and physiotherapists, significant policy and
      professional issues need to be addressed before such practice can be fully
      adopted.

PMID- 12047209
TI  - Hospital stay and discharge outcomes after knee arthroplasty: implications for
      physiotherapy practice.
AB  - Patient outcomes at discharge from acute care after knee arthroplasty were
      investigated in a prospective observational outcome study at three Melbourne
      public acute care hospitals during a five-month period from November 1999 to
      March 2000. The participants were 105 consecutive patients (35 at each hospital),
      with a mean age of 71 years. Outcome measures were length of stay, destination
      (home or rehabilitation), knee range of movement, and functional mobility at
      discharge from the acute care facility. During the study period, mean hospital
      length of stay across the three hospitals was 6.5 days, more than 30% less than
      the Victorian average for the preceding year. In that time, 56% of patients had
      achieved functional independence sufficient for discharge directly home, however
      only 36% were actually discharged home. The reasons identified for discharge to
      rehabilitation despite the achievement of sufficient functional independence
      included pressure on clinicians to decrease length of stay and the need to make
      decisions regarding discharge early in the post-operative recovery when the
      eventual patient outcome may still be unclear. Unnecessary discharges to
      rehabilitation increase the overall length of stay in the health care system and
      costs per patient. This finding suggests a method of risk screening is required
      to assist clinical decision making with regard to discharge.

PMID- 12047210
TI  - Multidimensional scaling analysis of techniques used by physiotherapists in
      Southeast Australia: a cross-national replication.
AB  - Much of the research concerning techniques used by physiotherapists has focused
      upon electrothermal agents, so neglecting fundamental questions concerning
      practice and differences in technique use. A recent study in England addressed
      these deficits, and determined that techniques were used in ordered combinations,
      which differentiate the profession into 'typologies' or specialities. The purpose
      of the present study was to determine whether a similar picture would emerge in
      Australia, and to determine the type and extent of technique use amongst
      Australian physiotherapists. This replication study comprised a questionnaire
      survey of 141 hospital physiotherapists working in Southeast Australia.
      Information concerning the range and frequency of techniques used over the
      preceding six months was obtained. Descriptive analyses indicated high frequency
      use of exercise therapy, manipulation, heat packs, massage and ultrasound.
      Multidimensional scaling revealed a clear structure concerning combination use of
      techniques, and a coherent typology based on this usage. Differentiation of the
      profession according to the typologies supports the specialist areas identified
      in England, namely respiratory, neurological and orthopaedic/musculoskeletal
      physiotherapy. A further subdivision of the latter was possible in Australia,
      with the emergence of both a manipulative speciality, and an exercise
      rehabilitation speciality. While this study confirms the findings of the earlier
      research, it identifies important differences in practice between Australia and
      England.

PMID- 12047211
TI  - Vertebral artery complications following gentle cervical treatments. (Comment on
      Mann T and Refshauge KM, Australian Journal of Physiotherapy 47: 255-266.).

PMID- 12047212
TI  - Sustainable graduate education and professional competency. (Comment on Crosbie J
      et al, Australian Journal of Physiotherapy 48: 5-7.).

PMID- 12047213
TI  - Change or disappear--a critical point for our profession. (Comment on Crosbie J
      et al, Australian Journal of Physiotherapy 48: 5-7.).

PMID- 12047214
TI  - Physiotherapists risk losing their identity. (Comment on Crosbie J et al,
      Australian Journal of Physiotherapy 48: 5-7.).

PMID- 12047215
TI  - Conclusions of Superthumb study may have clouded the issue of manual handling
      stress. (Comment on Maher CG et al, Australian Journal of Physiotherapy 48: 25
      30.).

PMID- 12047216
TI  - Criticism of Superthumb may be invalid. (Comment on Maher CG et al, Australian
      Journal of Physiotherapy 48: 25-30.).

PMID- 12047218
TI  - The Bobath concept has changed. (Comment on Critically Appraised Paper,
      Australian Journal of Physiotherapy 48: 59.).

PMID- 12047221
TI  - Precise mapping of breakpoints in conserved synteny between human chromosome 1
      and pig chromosomes 4, 6 and 9.
AB  - Previous comparative mapping suggested that at least five pig chromosomes (Sscr4,
      6, 9, 10 and 14) share homology with human chromosome 1 (Hsap1). A significant
      quantitative trait loci (QTL) for fat deposition has been identified on Sscr4
      that appears to be near the junction region between Sscr4 and Sscr9 relative to
      Hsap1. It is of interest to define the boundaries of conserved synteny between
      pig chromosomes and Hsap1 to use human map information to identify putative
      comparative positional candidates for this QTL. Eleven genes, including Janus
      kinase 1 (JAK1), Prostaglandin E receptor3 (PTGER3), urate oxidase (UOX),
      coagulation factor 3 (F3), vascular cell adhesion molecule 1 (VCAM1), ribosomal
      protein L5 (RPL5), POU domain, class 2, transcription factor 1 (POU2F1),
      coagulation factor 5 (F5), Prostaglandin endoperoxide synthase-2 (PTGS2), myosin
      binding protein H (MYBPH) and Antithrombin III (SERPINC1), were selected to
      refine the boundaries of the blocks of conserved synteny between Hsap1 and pig
      chromosomes. Pig sequence tagged sites (STSs) were developed and used to
      physically map these 11 genes using a somatic cell hybrid panel. Eight loci have
      been mapped by using fluorescent in situ hybridization (FISH) to improve map
      resolution. Heterologous FISH was used to refine the location of VCAM1 on human
      chromosomes. In addition, human yeast artificial chromosomes (YACs) were mapped
      by heterologous FISH on pig metaphases to refine the boundaries of the regions of
      homology between Sscr4 and Sscr9 on Hsap1. Results from this study suggest the
      precise break in conserved synteny on Hsap1 corresponding to the Sscr4/6 and
      Sscr4/9 transitions are most likely on the Hsap1p22 and Hsap1q24-25 regions,
      respectively. Further, our data predict that Hsap1q21-24 is a candidate region
      for the backfat QTL localized to Sscr4.

PMID- 12047222
TI  - A genome scan for quantitative trait loci affecting resistance to
      Trichostrongylus colubriformis in sheep.
AB  - A genome linkage scan was carried out using a resource flock of 1029 sheep in six
      half-sib families. The families were offspring of sires derived by crossing
      divergent lines of sheep selected for response to challenge with the intestinal
      parasitic nematode Trichostrongylus colubriformis. All animals in the resource
      flock were phenotypically assessed for worm resistance soon after weaning using a
      vaccination/challenge regime. After correcting for fixed effects using a least
      squares linear model the faecal egg count data obtained following the first
      challenge and the faecal egg count data obtained after the second challenge were
      designated Trait 1 and Trait 2, respectively. A total of 472 lambs drawn from the
      phenotypic extremes of the Trait 2 faecal egg count distribution were genotyped
      with a panel of 133 microsatellite markers covering all 26 sheep autosomes.
      Detection of quantitative trait loci (QTL) for each of the faecal egg count
      traits was determined using interval analysis with the Animap program with
      recombination rates between markers derived from an existing marker map. No
      chromosomal regions attained genome-wide significance for QTL influencing either
      of the traits. However, one region attained chromosome-wide significance and five
      other regions attained point-wise significance for the presence of QTL affecting
      parasite resistance.

PMID- 12047223
TI  - Mapping of the bovine blood group systems J, N', R', and Z show evidence for
      oligo-genetic inheritance.
AB  - Genes determining the bovine erythrocyte antigens were mapped by linkage
      analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a
      grand-daughter design were elucidated for the genes determining the erythrocyte
      antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ
      according to standard paternity testing procedures in the blood typing
      laboratories. Linkage analyses were performed with 248 microsatellite markers,
      eight SSCP markers and four polymorphic proteins and enzymes covering the 29
      autosomes and the pseudoautosomal region of the sex chromosomes. The number of
      informative meioses for the blood group systems ranged from 76 to 947. Blood
      group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen
      loci showed significant linkage to a single chromosome and were mapped
      unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and
      EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score
      values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to
      chromosome 17. However, the EAN' system previously known as part of the EAF
      system could be mapped to chromosome 5. In addition, the blood group systems EAJ,
      the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers
      on various chromosomes and also to other blood groups. The appearance of a single
      blood group system might be therefore either dependent on the existence of other
      blood group systems or because of an interaction between different loci on
      various chromosomes as is known in humans and in pigs.

PMID- 12047220
TI  - Role of synaptotagmin in Ca2+-triggered exocytosis.
AB  - The Ca(2+)-binding synaptic-vesicle protein synaptotagmin I has attracted
      considerable interest as a potential Ca(2+) sensor that regulates exocytosis from
      neurons and neuroendocrine cells. Recent studies have shed new light on the
      structure, biochemical/biophysical properties and function of synaptotagmin, and
      the emerging view is that it plays an important role in both exocytosis and
      endocytosis. At least a dozen additional isoforms exist, some of which are
      expressed outside of the nervous system, suggesting that synaptotagmins might
      regulate membrane traffic in a variety of cell types. Here we provide an overview
      of the members of this gene family, with particular emphasis on the question of
      whether and how synaptotagmin I functions during the final stages of membrane
      fusion: does it regulate the Ca(2+)-triggered opening and dilation of fusion
      pores?

PMID- 12047224
TI  - A new deletion mutation in bovine Claudin-16 (CL-16) deficiency and diagnosis.
AB  - Bovine claudin-16/paracellin-1 (CL-16/PCLN-1) deficiency is an autosomal
      recessive disorder caused by a 37-kb deletion mutation containing the first four
      exons of the CL-16 gene, which leads to the absence of the CL-16 transcript (type
      1 mutation). A PCR-based DNA test for the CL-16 mutation (type-1) was used to
      screen a herd of Wagyu cattle. A recent report suggested that affected cattle can
      be bred by dams diagnosed as normal, suggesting the presence of a new mutation in
      the CL-16 locus. We identified the new mutation as a 56-kb deletion containing
      exon-1 to -4 and 21-bp of exon-5 of CL-16, and refer to this as a type-2
      mutation. A DNA test for specific for this mutation was then established.

PMID- 12047225
TI  - Investigation of candidate genes for meat quality in dry-cured ham production:
      the porcine cathepsin B (CTSB) and cystatin B (CSTB) genes.
AB  - Excessive softness is a serious defect of dry cured hams which seems related to
      high activity of lysosomal cysteine proteinases, such as cathepsin B, in fresh
      pork muscles a few days after slaughtering. As it has been shown that cathepsin B
      activity has a moderate heritability in Italian Large White pigs we started a
      candidate gene approach to identify the gene(s) that affect(s) this parameter.
      Here, we studied two candidate genes: cathepsin B (CTSB) and cystatin B (CSTB).
      We amplified and sequenced porcine DNA fragments for these two genes that were
      used to identify polymorphisms by SSCP and polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis. Four and two alleles were
      detected at the CTSB and CSTB loci, respectively. Sequencing of the CSTB alleles
      showed a missense mutation that changes a codon for aspartic acid into a codon
      for asparagine in exon 3 of the gene. Allele frequencies for the two loci
      differed among the pig breeds studied (Large White, Landrace, Duroc, Belgian
      Landrace, Hampshire, Pietrain, Meishan, Cinta Senese, Casertana, Calabrese and
      Nero di Sicilia). Linkage, somatic cell hybrid panel and radiation hybrid panel
      analyses assigned CTSB to porcine chromosome (Sscr) 14 and CSTB to Sscr 13. The
      markers identified at the CTSB and CSTB loci were used in association studies
      with several traits of economic importance including parameters that may indicate
      the suitability of pig meat to produce dry-cured hams. Significant associations
      were observed between CTSB and back-fat thickness and between CSTB and average
      daily gain. In this study, cathepsin B activity was not associated with the
      polymorphisms identified at the CTSB and CSTB loci.

PMID- 12047226
TI  - DNA markers and crossbreeding scheme as means to select sires for heterosis in
      egg production of chickens.
AB  - Genotypes for 24 microsatellite markers, dispersed across the chicken genome,
      were used to predict progeny performance and heterosis for egg production (number
      and mass) in 'layers' (egg-type chickens). These markers were used to evaluate
      genetic distance between each of 39 sires sampled from two-layer male-lines;
      Rhode Island Red (RIR) and White egg Leghorn (Leghorn), and a DNA pool of 30
      randomly sampled females from a Brown-egg female line (Silver). Each sire was
      analysed for egg production across months in the laying period and cumulatively
      in each of three subperiods; onset (2 month), mid (9 month) and late (1 month).
      The average Reynolds' genetic distance between Leghorn sires and the Silver
      female line (theta;=0.6) was significantly higher than that between RIR sires and
      the Silver female line (theta;=0.5). Neither performance nor heterosis values in
      the RIR sire's daughters were associated with genetic distance values between
      sires and the Silver female line. On the other hand, performance as well as
      heterosis values of Leghorn's daughters were positively associated with genetic
      distance. This association was particularly evident in the mid-subperiod. If 25%
      of the most genetically distant Leghorn sires from the Silver female line had
      been selected in a single generation on the basis of DNA markers information
      only, average egg production of the crossbred daughters would have been improved
      by about nine eggs (3%). In principle, further improvement is possible if
      selection to increase genetic distance between the parental lines is carried on.

PMID- 12047227
TI  - Rapid isolation of CA microsatellites from the tilapia genome.
AB  - We have developed (CA)n microsatellite markers for the cichlid fish, Oreochromis
      niloticus using a variation of the hybrid capture method. The resulting genomic
      library was highly enriched in repetitive DNA with 96% of clones containing CA
      repeats. The number of repeats ranged from four to 45 with an average of 19. Two
      thirds of the sequenced clones had 12 or more repeats and sufficient flanking
      sequence to design primers. The resulting markers were tested in an F2 cross of
      O. niloticus x O. aureus. Nearly 90% of the markers amplified in this cross and
      74% of these were informative. This work demonstrates the importance of
      minimizing the number of polymerase chain reaction (PCR) amplification cycles
      before and after the enrichment steps to reduce PCR recombination and the
      generation of chimaeric clones.

PMID- 12047228
TI  - Assignment of porcine cyclin-dependent kinase 4 (CDK4) and oncogene c-mos (MOS)
      by nonradioactive nonfluorescence in situ hybridization.
AB  - Two pig genes, cyclin-dependent kinase 4 (CDK4) and the oncogene c-mos (MOS) were
      mapped by means of nonradioactive nonfluorescence in situ hybridization. Our
      approach was based on the detection of hybridized biotinylated probe by
      peroxidase conjugated extravidin and the reaction of peroxidase with its
      substrate diaminobenzidine (DAB) resulting in a dark precipitate. To increase the
      sensitivity of the method in single-copy gene mapping, two amplifications of the
      peroxidase signal were used: immunological amplification by biotinylated
      antiavidin, and peroxidase-catalysed deposition of biotinylated tyramide. Using
      this method, two 2-kb-long probes for the porcine genes CDK4 and MOS were mapped
      to pig chromosomes 5p12 and 4q14-15, respectively. Non-radioactive
      nonfluorescence in situ hybridization described here is a method of choice for
      gene mapping of short probes.

PMID- 12047229
TI  - A set of cattle microsatellite DNA markers for genome analysis of riverine
      buffalo (Bubalus bubalis).
AB  - One hundred and eight microsatellite primer pairs, originally identified from
      cattle, were evaluated for their applicability in buffalo. Eighty-one primer
      pairs (75%) amplified discrete products, and of these, 61 pairs (56%) gave
      polymorphic band patterns on a panel of 25 buffaloes. The mean number of alleles
      per polymorphic marker was 4.50 +/- 0.20, and the mean heterozygosity per
      polymorphic marker was 0.66 +/- 0.02. Successful genotyping of buffaloes using
      cattle specific primers suggests that the latter can be a valuable resource for
      genome analysis in bubaline species.

PMID- 12047230
TI  - Melanocortin-4 receptor (MC4R) genotypes have no major effect on fatness in a
      Large White x Wild Boar intercross.
AB  - The melanocortin-4 receptor (MC4R), a G-protein coupled receptor, is implicated
      in mediating the effect of leptin on food intake and energy balance. A previous
      candidate gene study reported an association between an MC4R missense mutation
      (Asp298Asn) and fatness, growth and feed intake in pigs. To assess this
      association further, we analysed the segregation of this missense mutation in
      relation to variation in fatness traits using a Wild Boar x Large White
      intercross. The Wild Boar and Large White founders were homozygous for different
      MC4R alleles. The MC4R was assigned to the expected region on pig chromosome 1.
      The statistical evaluation did not reveal any indication of a significant effect
      on fatness related traits in this pedigree.

PMID- 12047231
TI  - Genetic identity of two Indian pig types using microsatellite markers.

PMID- 12047232
TI  - PZE46 and PZE114: two bovine polymorphic microsatellite loci isolated from a
      placenta cDNA library.

PMID- 12047233
TI  - Seven SNPs in the porcine INSL3 gene encoding Leydig cell insulin like hormone.

PMID- 12047235
TI  - Linkage and cytogenetic mapping of the BCL9 gene to porcine chromosome 4.

PMID- 12047234
TI  - Cloning of the canine delta tubulin cDNA (TUBD) and mapping to CFA9.

PMID- 12047236
TI  - CSY234: a SINE-associated genetic and physical marker on bovine chromosome X.

PMID- 12047237
TI  - Assignment of the 2,4-dienoyl-CoA reductase (DECR) gene to porcine chromosome 4.

PMID- 12047238
TI  - BMP15 maps to the X chromosome in swine.

PMID- 12047239
TI  - Assignment of the porcine epidermal growth factor (EGF) gene to SSC8q2.3-q2.4 by
      fluorescence in situ hybridization and radiation hybrid mapping.

PMID- 12047241
TI  - Level of superoxide dismutase, glutathione peroxidase and uric acid in
      thioacetamide-induced cirrhotic rats.
AB  - Levels of superoxide dismutase and glutathione peroxidase were determined in
      blood and hepatic tissues of thioacetamide-induced cirrhotic rats and compared to
      levels in age-matched control animals. The plasma level of uric acid was also
      determined in these animals. A general decrease was noticed in the level of all
      the antioxidants examined as compared to the control. This decrease was
      statistically significant in the level of all the antioxidants studied, except
      for the level of superoxide dismutase in blood. A decrease in the antioxidant
      level may indicate an increase in free radical level and thereby an increase in
      cellular damage in cirrhotic rats. The changes in the level of antioxidants
      showed a direct correlation with the changes in the level of trace elements
      observed in our previous studies. These studies suggest that antioxidants alone
      or in combination with trace elements may have beneficial effects in treating
      liver cirrhosis.

PMID- 12047242
TI  - Distribution of beta-endorphin and substance P in the shoulder joint of the dog
      before and after a low impact exercise programme.
AB  - Beta-endorphin and substance P were immunolocalized in the articular cartilage,
      synovial membrane and fibrous joint capsule of dogs. Twelve adult greyhounds were
      randomly assigned to one of three groups: control, limited exercise, or
      regimented exercise. On day 0, biopsies of articular cartilage and joint capsule
      were obtained from the left shoulder joints of dogs receiving limited and
      regimented exercise. On day 72, biopsies of joint capsule from right and left
      shoulders and articular cartilage from the right shoulder joint were analysed for
      the presence of glycosaminoglycans (GAG) and for immunolocalization of substance
      P and beta-endorphin. Regimented exercise increased the presence of GAGs and
      immunolocalization of substance P and beta-endorphin in articular cartilage and
      synovial membrane compared to day 0 biopsies and untreated controls. Localization
      of beta-endorphin became prominent in and around the chondrocytes. Substance P
      was increased in chondrocytes and extracellular matrix. Concomitant changes in
      localization of beta-endorphin and substance P may have a role in the modulation
      of the microphysiological environment, metabolism, or function of joint tissues
      in response to low-impact exercise.

PMID- 12047243
TI  - The regional distribution and relative frequency of gastrointestinal endocrine
      cells in SHK-1 hairless mice: an immunohistochemical study.
AB  - The regional distributions and relative frequencies of some gastrointestinal
      endocrine cells in the eight portions (fundus, pylorus, duodenum, jejunum, ileum,
      caecum, colon and rectum) of the gastrointestinal tract of SKH-1 hairless mice
      were investigated using immunohistochemical methods and seven types of specific
      antisera against somatostatin, serotonin, glucagon, cholecystokinin (CCK)-8,
      secretin, pancreatic polypeptide (PP) and gastrin. In this study, somatostatin-,
      serotonin-, glucagon-, CCK-8-, secretin- and gastrin-immunoreactive (IR) cells
      were identified. Most of these IR cells in the intestinal portion were generally
      spherical or spindle-shaped (open-type cell) while cells that were round in shape
      (close-type cell) were occasionally found in the stomach regions. Their relative
      frequencies were varied according to each portion of gastrointestinal tract.
      Somatostatin-IR cells were found throughout the gastrointestinal tract except for
      the large intestine. Serotonin-IR cells were detected throughout the whole
      gastrointestinal tract and were the most predominant endocrine cell types in this
      species of mouse. Glucagon-IR cells were restricted to the fundus, occurring
      rarely. CCK-8-IR cells were observed in the pylorus, duodenum and jejunum with
      frequencies that were numerous, moderate and few, respectively. Peculiarly,
      secretin-IR cells were demonstrated in the whole intestinal tract with either few
      or rare frequencies. Gastrin-IR cells were restricted to the pylorus and were
      numerous. However, no PP-IR cells were found in this study. In conclusion, some
      peculiar distributional patterns of gastrointestinal endocrine cells were found
      in SKH-1 hairless mouse.

PMID- 12047244
TI  - Horse lumbrical muscle: possible structural and functional reorganization in
      regressive muscle.
AB  - An anatomical study of horse lumbrical muscle (Lm) was carried out by light and
      electron microscopy in combination with immunochemical and cytochemical methods.
      Paraffin sections were subjected to haematoxylin and eosin (H & E) and Masson's
      trichrome staining for morphometric analysis. Paraffin sections were also used
      for immunostaining by anti-PGP 9.5 for reaction with nerve-protein associated
      structures, anti-heat-shock protein 70 (hsp 70) for detection of gene expression
      changes, anti-fast myosin for the determination of muscle fibre types, and for
      detection of apoptotic gene expression of muscle fibres by the TUNEL method. The
      distribution of muscle fibre types on frozen sections was also examined by
      assaying ATPase (pH 4.2). We found that the proximal end of the tendon of the
      unipennate-shaped Lm binds to the deep digital flexor tendon, and the distal end
      of the Lm tendon connects to the medial surface of the palmar annular ligament.
      The Lm was not always present, but when found it varied in length greatly, up to
      8 cm (muscle part alone), and weighed less than 1 g. The Lm was white, pale, or
      reddish in colour depending on the ratio of muscle fibre and connective tissue
      contents. The semi-tendinized regressive Lm was composed of rich vasculature,
      peripheral nerves, and nerve-like organs similar to the neuromuscular spindle
      (NMS). The extrafusal muscle fibres (e-lm) that surround the NMS were replaced
      with a thick outer capsule of connective tissues (CT) in the Lm nerve-like organ,
      which we named the neurotendinous capsule (NTC) organ. NTC organs exist alone or
      as multiple structures (up to eight) surrounded by a common outer capsule at the
      outermost CT ring. The NTC possesses several intrafusal muscle fibres (ifm) just
      as the NMS does. That the ifm was associated with nerve endings was confirmed by
      anti-PGP 9.5 and electron microscopic observation. Some muscle fibres in ifm and
      e-lm reacted with anti-fast twitch myosin and with anti-hsp 70. The e-lm
      exhibited at least two fibre types, determined by ATPase (pH 4.2) assay. The ifm
      exhibited mainly type I (slow twitch) fibres. No apoptotic gene expression was
      detected in either ifm or e-lm, suggesting the Lm is a vital organ. The
      degenerating fibres observed in ifm and e-lm indicate that the turnover rate of
      cytoplasmic components is accelerated. We attribute this phenomenon to the
      necessity for adaptation to new environmental demands. The surprising finding of
      tubular aggregates (TAs) in ifm of the NTC organ suggests that the Lm is
      continuously adapting. Some results related to variation in diameter of the
      collagen fibrils, isolation of the NTC organ and the myofibrillar protein
      constituents are also discussed. In conclusion, the so-called regressive Lm has
      rich vasculature, many peripheral nerves, and newly described NTC organs. The
      induction of heat-shock protein, lack of apoptotic gene expression in ifm and e
      lm fibres, and TA formation in ifm suggest that horse Lm responds to
      environmental stress through reorganization and/or remodelling of cell
      constituents. We hypothesize that the horse Lm has lost its original role as a
      contractile element and changed to another function, likely as a vital nerve
      organ.

PMID- 12047245
TI  - The influence of stomach volume on the liver topography in cats.
AB  - The aim of this study has been to describe the effect of varying degrees of
      fullness of the stomach on liver topography in cats by means of the sectional
      anatomy of the abdominal cavity. Twenty-four adult healthy cats of both sexes and
      of different ages were used. The cats were divided into two groups. The first
      group had empty stomachs and the second group had filled stomachs. Eight cats
      were dissected. The remaining cats were frozen at - 20 degrees C, eight of these
      were then sectioned paramedially and the other eight were sectioned transversely.
      In the dissection and sections, it was observed that the liver shifted
      considerably to the right and craniodorsally in cats with full stomachs. In this
      article, the topographical anatomy of the liver according to varying stomach
      volumes is described in a manner that is useful to veterinary surgeons and
      clinicians. The sectional findings obtained from the paramedial and transverse
      sections provide information for computed tomography and magnetic resonance
      imaging.

PMID- 12047246
TI  - Characteristics of myofibres in the masseter muscle of mice during postnatal
      growth period.
AB  - Functional maturation of muscles is related to the constitutional proportion of
      muscle protein isoforms during development and growth. Although the mouse
      masseter muscle (MS) is classified as a fast limb muscle, its functions are
      different from those of a limb muscle. This study investigated the
      differentiation of myosin heavy chain (MHC) isoforms during the postnatal
      development periods in mouse MS and mouse tibialis anterior (TA), which is a fast
      limb muscle. Many anti-MHC slow-type-positive fibres were observed in neonatal MS
      and TA; these fibres decreased during development. Adult MS was composed of anti
      MHC fast-type-positive fibres. MHC isoforms in MS were composed of MHC-2a and MHC
      2d soon after birth. MHC-2b was expressed, but MHC-2a was not seen after 21 days.
      Expression of MHC-2b agreed with the weaning period, that is 2-3 weeks after
      birth. This fact suggested that the transformation from suckling to mastication
      changed the MHC isoforms during this period. In this study, the expressions of
      MHC-2b agree with the weaning period.

PMID- 12047247
TI  - Cyclical reproductive changes in the non-ciliated epithelia of the epididymis of
      birds.
AB  - The epididymis of two species of domestic birds, the domestic fowl (Gallus
      domesticus), duck (Anas platyrhynchos), and of domestic and feral guinea-fowl
      (Numida meleagris) was studied during the three main phases of the reproductive
      cycle (prepuberal, sexually mature and active, and sexually mature but inactive
      or resting) with a view to identifying major histological and ultrastructural
      changes associated with and distinctive for each phase. Rete testis cells
      accumulated numerous variably sized lipid droplets in all birds, as well as large
      heterogeneous and lipofuscin-containing dense bodies in the guinea-fowl, during
      the resting but not in the other phases. The principal or Type III cells of the
      connecting and epididymal ducts exhibited profound structural changes, including,
      but not limited to, rarefied cytoplasm, inconspicuous and general loss of
      sparsely granular endoplasmic reticulum, loss of secretory vesicles in the drake,
      and an enhanced and conspicuous presence of lipid droplets in the guinea-fowl.
      The rete cells appeared to be less sensitive than the Type III cells to a reduced
      level or absence of lumenal androgens. These phase-dependent changes may help to
      prevent or minimize discrepancies in the interpretation of the normal structure
      of the epididymis in birds during the sexually active phase, as distinct from the
      other two phases and their intermediate phases.

PMID- 12047248
TI  - Embryo transfer and embryonic capsules in the bobcat (Lynx rufus).
AB  - Bobcats (Lynx rufus) (n=22) were used to test a surgical embryo transfer protocol
      for wild felines. Five blastocysts were collected 8-14 days post-initial
      copulation (PIC). Translucent capsule-like structures were recovered at 12 days
      PIC and are the first report of such a structure in a felid. Endometrial fibrosis
      was observed in one cat but, in general, post-surgical fibrosis of the uterus did
      not seem to impede ova or embryo transport. One embryo underwent cryopreservation
      and this embryo plus two other transferrable embryos were placed in recipient
      cats during the course of the study. No pregnancies were maintained; but one non
      cryopreserved embryo was detected by ultrasound examination at 2 weeks post
      transfer. This study provides valuable groundwork for future studies and warrants
      optimism for continued research in this area.

PMID- 12047249
TI  - Musculus extensor digiti medii proprius and musculus extensor digitorum brevis
      manus - a case report of a rare variation.
AB  - The musculus extensor digiti medii proprius and musculus extensor digitorum
      brevis manus are anomalous extensor muscles of the hand. During the routine
      dissection of a white male cadaver a musculus extensor digiti medii proprius was
      seen on both hands and a musculus extensor digitorum brevis manus was seen on the
      left hand. The extensor medii proprius has a belly originating from the distal
      third of the ulna near the extensor indicis proprius and its tendon is inserted
      into the dorsal aponeurosis of the middle finger on both hands. On the left hand
      there was another anomalous muscle (musculus extensor digitorum brevis manus)
      which originated from the distal end of the radius, carpal ligaments and carpal
      joint capsule and inserted on the tendon of the extensor digiti medii proprius.
      This case is a multivariation of the hand extensor muscles and a musculus
      extensor digitorum brevis manus inserting on the musculus extensor digiti medii
      proprius has not been reported previously.

PMID- 12047251
TI  - Proceedings of the 8th Luigi Barbara Educational Training Workshop in Upper and
      Lower Gastrointestinal Diseases. Bologna, Italy, 26-27 October 2001.

PMID- 12047252
TI  - Review article: monitoring activity in ulcerative colitis.
AB  - The monitoring of patients with ulcerative colitis is easier than in patients
      with Crohn's disease for several reasons: the severity of symptoms and activity
      of inflammation tend to run parallel in ulcerative colitis when involvement of
      the large bowel is more extensive. The easy accessibility of the colonic mucosa
      by endoscopic and histologic examination provides further information concerning
      the degree of inflammation. In severe attacks, the patient must be admitted to
      hospital and monitored carefully. Clinical and laboratory parameters (such as
      daily stools, CRP, fever, haemoglobin, albumin, etc.) and plain abdominal X-ray
      are useful in monitoring the activity of the disease and to predict the outcome.
      In mild to moderate attacks, endoscopic and histologic evaluation are the best
      methods for choosing the appropriate treatment and for assessing response.

PMID- 12047253
TI  - Review article: medical treatment of severe ulcerative colitis.
AB  - Approximately 15% of patients with ulcerative colitis have a severe attack
      requiring hospitalization at some time during their illness. This treatment leads
      to a remission in 60-80% of patients and non-responders may require a total
      colectomy. Mortality in severe episodes of ulcerative colitis decreased from 31
      61% in the 1950s to 5-9% in the 1960s thanks to the introduction of steroids and
      to a policy of early colectomy. Recently, some new drugs have been shown to be
      effective in the treatment of severe steroid-refractory ulcerative colitis. This
      review concentrates on the clinical evaluation, prognostic factors and new
      developments in medical therapy in severe ulcerative colitis. A retrospective
      evaluation of a consecutive series of patients with severe ulcerative colitis
      admitted to a Gastroenterology Department in Torino, Italy, is also reported.

PMID- 12047254
TI  - Review article: treatment of mild to moderate ulcerative colitis and pouchitis.
AB  - The meta-analyses of published trials have shown topical therapy with 5
      aminosalicylic acid (5-ASA) to be the treatment of choice in active distal
      ulcerative colitis. Oral aminosalicylates are effective for both distal and
      extensive ulcerative colitis, but in distal colitis the rates of improvement and
      remission are usually lower than those reported for rectal 5-ASA therapy. An
      alternative to 5-ASA therapy is represented by the new steroids; budesonide and
      beclometasone dipropionate (BDP) enemas, the most extensively studied, have been
      shown to be as effective as conventional steroids but with a significantly lower
      inhibition of plasma cortisol. Patients who do not respond to 5-ASA or new
      steroids should be treated with oral steroids. Azathioprine or 6-mercaptopurine
      may be effective in patients who do not respond or cannot be weaned off steroids.
      Treatment of pouchitis is largely empirical and few controlled studies have been
      carried-out. Antibiotics are the treatment of choice and most patients make a
      good response to metronidazole or ciprofloxacin. Chronic refractory pouchitis may
      benefit from a prolonged course of a combination of antibiotics. Highly
      concentrated probiotics (VSL#3) are effective both for the prevention of
      pouchitis onset and the prevention of relapses.

PMID- 12047255
TI  - Review article: maintenance of remission in ulcerative colitis.
AB  - Seventy percent of patients with ulcerative colitis can expect to experience a
      relapse over a 12 month period. Sulfasalazine was the first drug demonstrated to
      reduce this relapse rate to 21 percent. Subsequent studies have demonstrated that
      5-aminosalicylic acid (5-ASA) is the main active component, and preparations
      containing only 5-ASA have similar efficacy to sulfasalazine. 5-ASA is readily
      absorbed from the small intestine; to achieve high a colonic lumenal
      concentration therefore requires special release formulation. A variety of 5-ASA
      preparations is available, differing in their release mechanism, efficacy and
      side effect profile. Most patients can be maintained in remission using oral 5
      ASA medication. For patients with distal or left sided disease the use of rectal
      5-ASA is also of proven benefit in maintaining remission. Some patients with
      frequent or severe relapses require stronger immunosuppression, and in these
      patients azathioprine or 6-mercaptopurine (6-MP) are of proven benefit.
      Azathioprine is also invaluable for maintaining remission in patients who have
      been treated with cyclosporin for a fulminant acute episode of colitis. The
      exciting spectre of natural bacterial therapies (probiotics) deserves further
      exploration.

PMID- 12047256
TI  - Review article: ulcerative colitis--surgical indications and treatment.
AB  - The indication for surgery is a balance between the severity of the disease
      despite full medical treatment and the potential disadvantages of surgery. The
      decision requires cooperation between gastroenterologist and surgeon. Colectomy
      with ileostomy and preservation of the rectum in the emergency setting is the
      accepted procedure and can rapidly restore the patient to normal health allowing
      withdrawal of anti-inflammatory medication. After recovery all surgical
      possibilities are then open for the future. The elective indications for surgery
      include failure of medical treatment, retardation of growth in a child or
      adolescent and neoplastic transformation. The choice of operation includes
      conventional proctocolectomy, restorative proctocolectomy (RPC) and colectomy
      with ileo-rectal anastomosis. Each has relative advantages and disadvantages. RPC
      is the commonest procedure. It offers a satisfactory outcome in 70-90% of
      patients with a cumulative failure rate of 10-15% over a 10 year period. Causes
      of failure include sepsis (50%), dysfunction (30%) and pouchitis (10%). In
      selected cases salvage surgery to avoid failure can be successful with rates of
      around 70% for outlet obstruction and fistulation and 50% for pelvic sepsis.

PMID- 12047257
TI  - Review article: monitoring the activity of Crohn's disease.
AB  - Crohn's disease is characterized by a chronic inflammation of the intestine of
      unknown aetiology. One of the main problems when treating patients with Crohn's
      disease, is the identification of patients undergoing early clinical relapse, for
      timely treatment and the possible prevention of complications. No sub-clinical
      markers are currently available that predict relapse during remission. Several
      parameters have been proposed for this purpose. Although none have proven useful,
      growing evidence suggests a possible benefit in the clinical management of
      Crohn's disease. Among these, we may identify: clinical behaviour, the
      characteristics of the host, clinical activity, markers of intestinal
      inflammation and markers of immune activation. In particular, the possible
      relationship between cytokine pattern and the clinical behaviour of Crohn's
      disease has been addressed. Overall, these observations suggest that mucosal
      immune activation is a feature of Crohn's disease, and may persist in the form of
      activated immunocompetent cells during remission. On the basis of this evidence,
      studies are currently investigating whether the down-regulation of immune
      activation markers is associated with clinical remission in Crohn's disease. It
      has been shown that higher mucosal levels of TNF-alpha and an increased state of
      activation of lamina propria mononuclear cells in patients with inactive Crohn's
      disease, are significantly associated with an earlier clinical relapse of the
      disease. These observations suggest that a persistent local immune activation
      during remission may represent a marker of early clinical relapse of Crohn's
      disease.

PMID- 12047258
TI  - Review article: medical treatment of active Crohn's disease.
AB  - Crohn's disease, a heterogeneous inflammatory process that can affect various
      sites in the gut, presents an ongoing management challenge for the clinician. The
      treatment of active disease and complications is one of the main goals in the
      therapy of this disease. New therapies are aimed at delivering the active
      compounds to the diseased site, reduction or suppression of enteral flora and
      modulation of more focal targets within the immune response. The use of
      antibiotics in the therapy of Crohn's disease is gaining popularity, on the
      grounds that intestinal bacteria may play a role in the pathogenesis of Crohn's
      disease lesions. Metronidazole is one of the most widely used antibiotics,
      especially in the treatment of perianal disease. Corticosteroids are the
      mainstays of medical treatment in active Crohn's disease and induce the remission
      of symptoms in about 60-80% of patients. The use of immunosuppressive agents,
      such as cyclosporine and methotrexate, in patients with active disease resistant
      to standard therapy has gained acceptance in recent years. With new therapies the
      outlook for patients with Crohn's disease is more optimistic than it has been for
      a long time.

PMID- 12047259
TI  - Review article: the management of refractory Crohn's disease.
AB  - Refractoriness to conventional therapy is a common and intriguing problem in
      Crohn's disease patients. At the present time there is no agreement on its
      definition and several mechanisms are involved in its determination.
      Immunosuppressors, such as azathioprine (AZA), 6-mercaptopurine (6MP) and
      methotrexate (MTX) are effective drugs for controlling the inflammatory process
      and avoid chronic glucocorticosteroid treatment and its related side-effects.
      Recently, the introduction of tumour necrosis factor antibodies (infliximab) has
      dramatically changed the natural history of Crohn's disease and its therapeutic
      approach. Several studies have determined the efficacy, mechanisms and safety of
      infliximab. However, this molecular approach has also left several questions
      unanswered about the mechanisms of refractoriness, possible concomitant
      treatments and long-term safety and efficacy.

PMID- 12047260
TI  - Review article: Crohn's disease--the role of nutritional therapy.
AB  - Maintenance of adequate nutrition is of obvious importance in the management of
      patients with Crohn's disease. Exclusive parenteral nutrition can achieve high
      rates of remission, but this is not usually necessary since exclusive elemental
      and polymeric enteral regimes can yield similarly good results. Comparison of
      exclusive enteral formula feeding with steroid treatment favours steroids only
      because compliance is less complete for the restrictive nutritional regimes, and
      formula feeds should always be the first choice in the growing child with active
      Crohn's disease. It is probable that the nature of the lipid provided in Crohn's
      diets is clinically important, and there is some evidence that the n-3 fatty
      acids are beneficial. Continuation of nutritional supplements once remission has
      been obtained appears valuable even when malnutrition is not a major
      consideration.

PMID- 12047261
TI  - Review article: a critical approach to new forms of treatment of Crohn's disease
      and ulcerative colitis.
AB  - Most patients with inflammatory bowel disease can be managed with conventional
      immunosuppressive therapy. The choice of agents to prevent relapses of
      inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies
      in animal models of inflammatory bowel disease indicate that chronic intestinal
      inflammation results from enhanced immune responses to bacteria that are present
      normally in the lumen. Loss of tolerance, an abnormal function or defective
      healing of the mucosal barrier may all give raise to chronic intestinal
      inflammation. This hypothesis is the basis of new therapies aimed at either
      decreasing the levels of luminal bacterial antigens and/or selectively blocking
      detrimental mucosal immune responses. Anti-TNF is an example of this novel
      approach that is very effective in Crohn's disease. The use of biological therapy
      is costly, however, and the long-term complications are not yet known. The recent
      increase of tuberculosis in patients treated with anti-TNF indicates that careful
      monitoring is necessary. It is clear that the new forms of treatment may play an
      important role in tailoring the appropriate drug to a specific group of patients.
      However, for the time being, fine-tuning in the use of conventional
      immunosuppression is necessary. New knowledge in the pharmacogenetics of these
      compounds allows improvements to be made in their use. It is to be hoped that a
      critical approach in the use of current and future drugs, taking into account the
      advances in the aetiopathogenesis of inflammatory bowel disease, will contribute
      to the quality of life of patients with inflammatory bowel disease.

PMID- 12047262
TI  - Review article: indication and type of surgery in Crohn's disease.
AB  - The large majority of patients affected by Crohn's disease require surgery during
      their clinical history. Radical resection originally advocated for Crohn's
      disease does not decrease the recurrence rate, and repeated resections predispose
      patients to the development of short-bowel syndrome. Over the last few years,
      conservative surgery has become accepted by many authors as a safe means of
      treating obstructive Crohn's disease. In this review article we analyse the
      efficacy and safety of conservative techniques, in comparison with resective
      surgery. Indications, advantages and technical aspects of resective and
      conservative surgery are reported. The experience with 489 patients treated for
      complicated or treatment refractory Crohn's disease in our Institution suggests
      that strictureplasty is a safe and effective procedure in many cases, as reported
      by other authors. The risk of cancer in areas of active disease as in stenosis
      treated with strictureplasty seems to be negligible. Resective surgery still
      represents the 'gold standard' in patients with perforating Crohn's disease;
      however, conservative surgery, usually contraindicated in perforating Crohn's
      disease, can be advocated in patients with localized perforating disease
      presenting an actual risk of short bowel syndrome.

PMID- 12047263
TI  - Review article: gastro-oesophageal reflux disease--pathophysiological issues of
      clinical relevance.
AB  - Gastro-oesophageal reflux disease is a multifactorial disorder in which the
      pathophysiological mechanisms are variably combined in different patients. Motor
      dysfunction of the lower oesophageal sphincter (LOS) and, possibly, the proximal
      stomach is a major cause of the increase in the number of reflux episodes.
      Transient LOS relaxation is the main mechanism of reflux in many patients with
      endoscopically negative disease, whereas a hypotensive LOS becomes relevant only
      in patients with oesophagitis. Alterations in primary and secondary peristalsis
      contribute to the increased oesophageal acid exposure by delaying clearance. The
      presence of a hiatus hernia, especially when voluminous and/or non-reducible,
      increases the number of reflux episodes by mechanically weakening the oesophago
      gastric junction, and impairs oesophageal clearance. Hypersensitivity to acid is
      often present and contributes to the clinical manifestations of the disease,
      whereas oesophageal hypersensitivity, both to chemical and mechanical stimuli,
      plays a predominant role in a subset of patients. Increased concentrations of
      noxious compounds in the oesophageal refluxate may contribute to the development
      of anatomical lesions, but this is still a matter for debate. The clinical
      relevance of Helicobacter pylori infection and of mucosal defensive factors still
      needs to be fully elucidated.

PMID- 12047264
TI  - Review article: treatment of mild and severe cases of GERD.
AB  - GERD prevalence continues to rise in contrast to peptic ulcer disease. The
      spectrum contains reflux esophagitis and so-called 'endoscopy-negative GERD' or
      'non-erosive GERD' (NERD) or S-GERD and patients with 'normal' overall 24-h
      esophageal acidification but with a high 'symptom-index'. The majority of reflux
      patients will not need endoscopy initially. Prompt referral for endoscopy is
      indicated only if the patient has atypical symptoms or alarm symptoms such as
      dysphagia, anemia, weight loss, severe abdominal pain, or pain that does not
      respond to acid neutralization or suppression, or develops symptoms after the age
      of 50 years. Antireflux therapy consist of raising the head of the bed,
      maintaining normal weight, and avoidance of foods and drugs that precipitate
      symptoms, together with antacids or over-the-counter H(2) receptor antagonists
      (H(2)RAs). If symptoms persist after these simple measures or if antacids or
      H(2)RAs are needed quite often, then a more formal first-line treatment should be
      started. Many experts feel that a stepdown approach instead of a stepup approach
      is clinically and economically a more appropriate way of installing such first
      line therapy. Physicians increasingly consider prescribing a (low- or standard
      dose) once-a-day proton pump inhibitor (PPI) as firstline therapy. If symptoms
      recur after 4-week trial or are in sufficiently relieved, then the patient should
      be referred for endoscopy. Endoscopy may reveal no abnormalities (NERD) or
      evidence of reflux-induced damage. Treatment of endoscopy-negative reflux disease
      should be directed towards rapid relief of symptoms and then maintenance of
      relief using minimum effective therapy. Responses to PPIs are somewhat lower in
      endoscopy-negative patients compared to esophagitis. Some form of long-term
      therapy is needed in the majority of patients. 'On demand' PPI therapy to control
      reflux symptoms is a new and attractive option. The goal of treatment of GERD
      should be to relieve symptoms and to heal lesions. Symptom severity and much less
      endoscopic abnormalities, drives the therapy. When symptoms are mild or
      intermittent and when esophagitis is absent or minimal, standard dose PPI is
      usually reinstituted. If there is moderate or severe esophagitis or if symptoms
      are particularly troublesome, then the patient should start again with standard
      dose PPI therapy once a day, but not uncommonly a b.i.d. dosage maybe necessary.
      Once a dose of the acid suppressant that relieves symptoms is found, this dose
      should be maintained for a period of 3 months. After this time, an attempt should
      be made to reduce the dose. A plan should be formulated for long-term treatment.

PMID- 12047265
TI  - Review article: cost-effectiveness of different GERD management strategies.
AB  - Recent data on gastro-oesophageal reflux disease management strategies suggest
      that the indirect costs of reflux disease are high, and that inadequate treatment
      is associated with significant out-patient costs for patients. Long-term
      management strategies now focus on discontinuous therapy for some subgroups of
      patients. On-demand therapy is particularly attractive for patients who have no
      mucosal disease.

PMID- 12047266
TI  - Review article: gastric cancer and Helicobacter pylori.
AB  - Gastric cancer is the second commonest cause of death from malignancy in the
      world. Its pathogenesis is comparatively well understood and its aetiology
      multifactorial. Non-cardia gastric cancer usually arises in a stomach that has
      been inflamed over a long period and where atrophy and intestinal metaplasia have
      supervened. The commonest cause of gastric inflammation is infection with
      Helicobacter pylori. Colonization with this organism increases the relative risk
      of developing this cancer by about six [Helicobacter and Cancer Collaborative
      Group. Gut 2001; 49: 347-53]. Its likelihood increases with the severity and
      extent of the gastritis. Severity is influenced by the virulence of the infecting
      organism, the genetics of the host, bile reflux, dietary factors and the presence
      of hypochlorhydria which influences the extent, as well as the severity, of the
      inflammation. The only predisposing factor which can easily be manipulated is H.
      pylori infection, which can be successfully treated in 80-90% of cases using a 1
      week therapeutic regimen.

PMID- 12047267
TI  - Review article: after gastritis--an imaginary journey into a Helicobacter-free
      world.
AB  - This article explores the consequences of the world-wide trend that may result-
      at different times for different populations--in the disappearance of
      Helicobacter pylori and gastritis. After a brief historical introduction, some of
      the factors that contribute to the decrease in the prevalence of H. pylori are
      presented. The most apparent results of this trend in the industrialized world
      have been a decrease in the incidence of peptic ulcer and distal gastric
      adenocarcinoma. However, some other conditions of the upper digestive tract, such
      as acid reflux disease and adenocarcinoma of the cardio-oesophageal junction have
      been increasing. This simultaneous increase has led to the speculation that it
      may be causally related to the decreased prevalence of gastritis, and currents of
      thought supporting a laissez faire attitude with regards to H. pylori infection
      have developed. If these trends continue, future research aimed at understanding
      the pathogenesis of H. pylori-related conditions, including gastric
      carcinogenesis, will hinge on access to populations in which H. pylori is still
      highly prevalent, and on further refinement of the recently introduced Mongolian
      gerbil model.

PMID- 12047268
TI  - Review article: dyspepsia: how to manage and how to treat?
AB  - Recent guidelines for dyspepsia, defined as pain or discomfort centred in the
      upper abdomen, emphasize that in younger patients with no alarm features and not
      taking nonsteroidal anti-inflammatory drugs, testing for Helicobacter pylori and
      treatment of the infection if present is a standard of care. If H. pylori is not
      present, empirical management (e.g. acid suppression) is often prescribed. It is
      further recommended that if patients relapse or fail to respond to treatment then
      upper endoscopy be undertaken. However, these guidelines have become
      controversial for a number of reasons. Firstly, the prevalence of H. pylori
      infection is falling as is the incidence of peptic ulcer disease due to the
      infection. Idiopathic peptic ulcer disease is also being increasingly recognized.
      Furthermore, the cost-effectiveness of endoscoping treatment failures has been
      questioned, as the yield is low and patient management is usually not altered.
      Finally, it remains controversial whether the treatment of H. pylori infection in
      functional dyspepsia is of value, and two recent high quality meta-analyses have
      reached diametrically opposite conclusions. Alternative strategies, such as
      initially treating with acid suppression and then considering H. pylori infection
      in those who fail have been suggested, as has in low H. pylori prevalent regions
      the abandonment of a test-and-treat strategy. However, appropriate management
      trials of these alternative strategies in primary care are lacking. The
      management of patients with functional dyspepsia who fail initial antisecretory
      therapy is now difficult; prokinetics have fallen into some disrepute. Tricyclic
      antidepressants (at a low dose) may be useful in a subset, but adequate trials
      are lacking.

PMID- 12047269
TI  - Review article: Helicobacter pylori infection from pathogenesis to treatment--a
      critical reappraisal.
AB  - The main areas of this review are Helicobacter pylori and disease pathogenesis;
      the relationship of H. pylori to lower gastrointestinal diseases, liver disease
      and extra-gastrointestinal conditions; the relationship of H. pylori to gastro
      oesophageal reflux disease; infection in the very young and very old; diagnostic
      techniques; and management of H. pylori infections with particular emphasis on
      eradication regimens and antibiotic resistance.

PMID- 12047299
TI  - Hormonal replacement therapy and ovarian cancer.

PMID- 12047270
TI  - Review article: esomeprazole in the treatment of Helicobacter pylori.
AB  - Proton pump inhibitor-based triple therapy is the most commonly used treatment
      for eradication of Helicobacter pylori, with pooled eradication rates of
      approximately 90%. In the USA, per protocol eradication rates with 10-day proton
      pump inhibitor-based triple therapy are approximately 85%. Esomeprazole, a new
      proton pump inhibitor that is the S-isomer of omeprazole and produces a greater
      inhibition of acid secretion than omeprazole, has recently been evaluated in the
      treatment of H. pylori. Seven-day twice daily triple therapy with esomeprazole 20
      mg, amoxicillin 1 g and clarithromycin 500 mg provided intention-to-treat
      eradication rates of 86-90% and per protocol eradication rates of 90-91% in
      duodenal ulcer patients in Europe and Canada. Ten-day triple therapy with
      esomeprazole 40 mg q.d.s., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d.
      achieved intention-to-treat eradication rates of 77-78% and per protocol
      eradication rates of 84-85% in USA duodenal ulcer patients. Thus, esomeprazole
      triple therapy with amoxicillin and clarithromycin is effective in the treatment
      of H. pylori, with eradication rates comparable to previously studied proton pump
      inhibitor-based triple therapies.

PMID- 12047300
TI  - Can changes in sex hormone binding globulin predict the risk of venous
      thromboembolism with combined oral contraceptive pills?
AB  - BACKGROUND: Recent studies have indicated that the risk of thromboembolic disease
      (VTE) in users of combined oral contraceptive pills (COCs) varies not only with
      estrogen dose, but also with the progestogen in pills with the same estrogen
      dose. The aim of this article is to discuss sex hormone binding globulin (SHBG)
      as a marker of estrogenicity and as a surrogate indicator for the potential risk
      of VTE in users of COC. MATERIAL AND METHODS: Using data from the literature, we
      investigated the relationship between the risk of VTE with various COCs and their
      effects on SHBG. We also collected data on the effects on SHBG by some combined
      preparations, where there are no VTE data. RESULTS: There appears to be a
      relationship between the risk of VTE and the effect on SHBG. Monophasic
      preparations containing levonorgestrel, having the lowest risk of VTE, cause an
      average SHBG increase of around 50%. COCs containing desogestrel or gestodene
      cause an average SHBG increase of 200-300%. A preparation with cyproterone
      acetate, carrying a higher risk of VTE than desogestrel and gestodene, cause a
      300-400% SHBG increase. With the recently developed combined preparations, there
      is a 150% SHBG increase with norgestimate and a 250-300% increase with
      drosperinone and dienogest. CONCLUSIONS: We propose that the change in SHBG with
      a COC could be interpreted as a measure of total estrogenicity and used as a
      predictor of the risk of VTE. Preparations containing drosperinone, dienogest,
      cyproterone acetate and norgestimate are equally or more estrogenic than the more
      thoroughly studied COCs, containing desogestrel or gestodene and should not be
      considered a safer substitute.

PMID- 12047301
TI  - Mother and child health care in Kabul, Afghanistan with focus on the mother:
      women's own perspective.
AB  - BACKGROUND: The study examined the pattern of utilization of Maternal and Child
      Health (MCH)-services of women with child-bearing experience in a suburb of city
      Kabul. METHODS: A semi-structured questionnaire administered to 100 women in the
      community and 40 in the maternal hospital. Interviews and observations in the
      local MCH-clinic were used to collect the relevant information. RESULTS: Sixty
      one of the 100 women in the community delivered at home exclusively, 35 having
      experienced both home and institutional deliveries, four women had hospital
      childbirths only. Approximately half of the women decided about utilizing the
      modern MCH services themselves. Women valued in the MCH-clinic mainly medical
      care and vaccinations. Delivery was seen primarily as a technical event, but when
      probed more deeply it was obvious, that fear of death was the driving power for
      decisions made. With at-home deliveries female relatives were preferred as birth
      assistants. If outside assistance was required, trained midwives were preferred
      rather than traditional birth attendants. Institutional delivery was seen as the
      last resource for complicated deliveries, but was also esteemed by many because
      of the security and cleaness. Professional skill, but also empathy and justice
      were appreciated in professionals. CONCLUSIONS: Promoting rooming-in and early
      breast feeding in the maternity wards, ongoing education of the MCH-staff about
      communication skills, ethics and teaching methods, dialogue with decision makers
      on all levels in the society about MCH including family planning, ongoing
      training and support of community midwives (dayas) in the community by local MCH
      staff, adequate supplies, inexpensive services, incentive money for the competent
      staff members are recommended.

PMID- 12047303
TI  - Self-reported reproductive outcome and implications in relation to use of care in
      women in rural Zimbabwe.
AB  - BACKGROUND: In order to assess morbidity and health care utilization in
      developing countries, health interview surveys are often used. The aim of this
      paper is to explore morbidity, health care utilization during pregnancy and
      pregnancy outcome as reported by women in rural Gutu district, Zimbabwe. METHODS:
      The study was cross-sectional, performed 1992-93 in 12 villages selected at
      random. Women aged 15-44 years (n = 1213) were interviewed concerning their
      reproductive history, use of maternity care and complications during
      pregnancy/labor during their latest pregnancy. RESULTS: The perinatal mortality
      rate (PMR) for all the completed pregnancies (889 women had completed 3601
      pregnancies) was 23/1000 total births. The attendance rate for antenatal care was
      high (94%). Elevated blood pressure was the most commonly reported late pregnancy
      complication, and a prolonged labor, i.e. 24 h or more, the most common
      complication during delivery. Out of women whose latest pregnancy did not end in
      an early or late abortion (n = 831) the cesarean section rate was 6.3%. The PMR
      was 8.4/1000 for their latest pregnancy. Institutional deliveries were preferred
      by the majority of women, with hospital and clinic deliveries constituting 58%
      and 27% of deliveries, respectively, while 15% delivered at home. Long-term
      complications were few, and only 14 (1.6%) women reported a current health
      problem, which they related to previous pregnancies. CONCLUSIONS: Antenatal
      attendance rate was high. The majority of women preferred institutional
      deliveries. Few women reported complications, which were not taken care of in the
      health service. Long-term complications related to previous pregnancies were few.

PMID- 12047302
TI  - Maternal height, birthweight and cephalo pelvic disproportion in urban Nigeria
      and rural Malawi.
AB  - BACKGROUND: Cephalo pelvic disproportion (CPD) has been attributed to short
      stature. It has been suggested that nutritional supplementation to promote linear
      growth would increase birthweight and the risk of CPD. The objective of this
      study was to examine the factors associated with CPD, with particular reference
      to birthweight, stature, parity and maternal age. DESIGN: Factors associated with
      CPD were analyzed using data abstracted from a detailed early hospital report
      from Ibadan, Nigeria and from a recent rural pregnancy study conducted in the
      Shire Valley, Malawi. RESULTS: In Nigeria, of 107 CPD cases admitted to hospital
      in Ibadan during 1953-54, 79% were women > 20 years. Birthweight values increased
      significantly with age and parity. In 19.6% of cases, the baby had a low
      birthweight (< 2500 g). In Malawi, among the 1523 women delivering, the incidence
      of CPD was 2.3%. Of the 35 cases of CPD, only four were adolescents. Birthweights
      increased with increasing parity, age and height (p < 0.001). In 6.4% of CPD
      cases, the baby had a low birthweight. Nulliparity (OR 4.0; CI 1.7-9.3; p =
      0.0001), birthweight >or= 3400 g (OR 4.6; CI 2.1-10.0; p = 0.0001) and height
      <or= 154 cm (OR 3.8; CI 1.8-7.9; p = 0.0003) were associated with an increased
      risk of CPD. Adolescent mothers were less likely to experience CPD (OR 0.3; C.I.
      0.8-0.9; p = 0.03). CONCLUSIONS: Adolescents are not at high risk of CPD.
      Nutritional supplementation of girls and adolescents should not be discouraged
      for fear of increasing the risk of CPD by improving birthweight. When CPD is
      present, it may result from childhood rickets and calcium deficiency.

PMID- 12047304
TI  - Pregnancy outcome after suicide attempt by drug use: a Danish population-based
      study.
AB  - BACKGROUND: It is important to study the side-effects of drugs taken during
      pregnancy, however the findings are difficult to interpret because of a low
      exposure level, uncertainty of actual drug consumption and confounding by
      indication. Experience from accidental or intended drug intoxications may bypass
      some of these methodological shortcomings. Our aim was to examine reproductive
      failures and child health following a single drug overdose taken prior to or
      during pregnancy. METHODS: Women diagnosed with a drug intoxication during
      pregnancy were identified in the Regional Hospital Discharge Registry of North,
      Jutland from 1977 to 1999 by linkage of diagnoses for abortion and delivery with
      diagnoses for intoxication. Hospital medical records were reviewed to obtain data
      on drug use, dosage, and pregnancy outcome (legally induced
      abortion/miscarriages/data on birth outcome). The hospitalization history of the
      children was followed for a mean of 9 years with a maximum of 20 years. RESULTS:
      Of 122 women studied, 44 wanted an elective abortion, 17 experienced miscarriage,
      and 61, exposed mainly to weak analgesics and psychotropic drugs, gave birth to
      62 infants. We estimated the proportion of miscarriage to be almost doubled,
      whereas there was no increased risk of congenital abnormalities or prematurity in
      women exposed to a drug overdose compared with the background population.
      CONCLUSIONS: A drug overdose shortly before or during pregnancy seems to be
      associated with a substantially increased risk of miscarriage, but there was no
      increase in fetal pathology at birth among fetuses surviving till birth.

PMID- 12047305
TI  - Termination of third-trimester pregnancy before term with gemeprost vaginal
      pessaries.
AB  - OBJECTIVE: Determination of the efficacy and side-effects of the synthetic
      prostaglandin analog gemeprost for termination of pregnancy in the third
      trimester. PATIENTS: Retrospective record study of 40 women who had undergone
      third trimester termination of pregnancy before term by serial administration of
      gemeprost because of intrauterine fetal death or hopeless fetal prognosis.
      Patients with multiple pregnancy, a Bishop score > 5, contractions or
      contraindications to prostaglandins were excluded. METHODS: Gemeprost vaginal
      pessaries (1-mg) were given at 6-hourly intervals until labor intervened. The
      main parameter studied was the induction-delivery interval, the length of time
      between administration of the first dose and delivery. Statistical analysis was
      performed with the chi-square and the Mann-Whitney U-test. RESULTS: The median
      induction-delivery interval was 14.4 h (range 3-48 h). Delivery occurred within
      12 h in 17 women (42.5%), within 24 h in 27 women (67.5%) and within 36 h in 37
      women (92.5%). An average of 2.6 doses were given per patient. Multigravidae had
      a significantly shorter induction-delivery interval than primigravidae (p <
      0.01). A total of 87.5% women required analgesia. Side-effects were infrequent.
      CONCLUSIONS: The administration of gemeprost vaginal pessaries represents an
      efficient method with few side-effects for the induction of labor in the third
      trimester, provided patients are chosen carefully and monitored closely.

PMID- 12047306
TI  - Longitudinal umbilical vein blood flow changes in normal and growth-retarded
      fetuses.
AB  - OBJECTIVE: To explore whether the umbilical vein blood flow of growth-retarded
      fetuses with normal Doppler parameters changes over time differently to that of
      normally grown fetuses. METHODS: Fifteen consecutive women whose fetus was
      diagnosed to be growth restricted were compared with 30 women whose fetus was
      normally grown. Two ultrasonographic evaluations were conducted at 2-weekly
      intervals (+/- 2 days) in all cases. At each sonographic evaluation, umbilical
      vein blood flow parameters were obtained by digital color Doppler velocity
      profile integration. To allow comparisons among fetuses, the umbilical vein blood
      flow per minute was normalized for abdominal circumference. RESULTS: The absolute
      vein blood flow was lower in growth-retarded than in normally grown fetuses (209
      ml/min +/- 73 vs. 313 ml/min +/- 72, p < 0.01). The median (range) umbilical vein
      blood flow normalized for abdominal circumference was significantly lower in
      growth-retarded than in normally grown fetuses at the first [0.70 (0.32; 1.15)
      vs. 1.11 (0.65; 2.07), p < 0.05] and at the second [0.71(0.30; 1.09) vs. 1.14
      (0.69; 2.05), p < 0.05] sonographic evaluation. The difference in umbilical vein
      blood flow normalized for abdominal circumference between the second and the
      first examination was significantly lower in growth-retarded than in appropriate
      for gestational age fetuses [-0.005 (- 0.08; 0.06) vs. 0.02 (- 0.08; 0.1), p <
      0.05]. CONCLUSION: This study demonstrates that umbilical vein blood flow
      normalized for biometric parameters is lower in growth-retarded fetuses than in
      healthy fetuses even in the absence of umbilical artery Doppler abnormalities.

PMID- 12047307
TI  - Doppler ultrasonography in singleton pregnancies at risk of intrauterine growth
      retardation-- a national estimate.
AB  - BACKGROUND: In order to assess the organizational and economical implications of
      Doppler ultrasonography used in high risk pregnancies, a national estimate of the
      use in singleton pregnancies with risk of small for gestational age (>2 SD below
      mean birthweight) (SGA) or intrauterine growth retardation (IUGR) was needed.
      METHODS: Through retrospective analyzes of both national registry data, and local
      clinical and ultrasonic records from Copenhagen University Hospital annual
      populations of singleton pregnant women with suspected IUGR and/or infants born
      SGA were described. The antenatal care program for assessing pregnancies with
      suspected IUGR was described. RESULTS: In 1996 2.8% of all singleton infants were
      born SGA. The population had increased risk of perinatal mortality and morbidity,
      and about 40% had labor induced or were delivered by caesarean section, compared
      to 15% of the infants with normal birthweight. In the local population 79 (3.3%)
      of singleton infants were born SGA and 2/3 of these were considered SGA or IUGR
      before delivery. Of all singleton pregnancies, a total of 88 (3.7%) were assessed
      by ultrasonic fetometry because of a risk or clinical suspicion of SGA, and 49
      (55.7%) of these pregnancies resulted in a SGA infants. Combining national and
      local data it is estimated that in Denmark, about 2000 women (3.1%) will be
      referred for ultrasonic fetometry each year because of a risk or clinical
      suspicion of SGA and have a mean of 2.5 fetometries. About 75% (1500) will be
      further assessed by Doppler ultrasonography and have a mean of 3.4 Doppler
      examinations. CONCLUSION: The annual number of Doppler ultrasonography
      examinations in singleton pregnancies with increased risk of or signs of IUGR is
      estimated to be about 5000.

PMID- 12047308
TI  - Is mid-trimester maternal serum inhibin-A a marker of preeclampsia or
      intrauterine growth restriction?
AB  - BACKGROUND: To evaluate maternal serum Multiple of Median inhibin-A in mid
      trimester blood samples of women who subsequently developed preeclampsia,
      gestational hypertension and intrauterine growth restriction and controls. Also,
      to verify whether this marker is related to these pathological conditions.
      METHODS: Retrospective analysis of serum samples from a bank of stored serum,
      originally taken for Down's syndrome screening over 15-18 weeks, was performed.
      The sample consisted of 20 patients with gestational hypertension, 20 patients
      with preeclampsia, 10 patients with intrauterine growth restriction and 40
      controls. RESULTS: No statistically significant difference of inhibin-A Multiple
      of Median values between the control group and the preeclamptic or gestational
      hypertension groups was found. There was a statistically significant elevation in
      the intrauterine growth restriction group in comparison with the control group,
      and the same was true for each subgroup of gestational hypertension and
      preeclampsia complicated by intrauterine growth restriction. CONCLUSION: Elevated
      maternal inhibin-A concentrations in the second trimester are strongly associated
      with intrauterine growth restriction and not with preeclampsia, as previously
      stated.

PMID- 12047309
TI  - The term breech presentation. A retrospective study with regard to the planned
      mode of delivery.
AB  - BACKGROUND: To analyze retrospectively a large group of term breech and vertex
      deliveries, with regard to the influence of the mode of delivery on the frequency
      of fetal and maternal complications. METHODS: All singleton breech deliveries
      after completed 36 weeks of pregnancy, with a live fetus, delivered at Rogaland
      Central Hospital, from September 1 1996 to the May 10 2001 were included (n =
      575). Correspondingly as a control group, 582 cases in vertex presentation were
      analyzed. RESULTS: Planned vaginal delivery (VD) for the fetus in breech
      presentation (n = 448) in comparison with elective caesarean section (CS) (n =
      127) increased early neonatal morbidity (3.6% vs. 0%). The frequency of Apgar
      scores < 7 at 5 min also increased (4.2% vs. 0.8%), as well as umbilical artery
      pH < 7.0 (4.4% vs. 0%), and referrals to the neonatal intensive care unit (NICU)
      (15.8% vs. 6.3%). Corresponding figures for planned VD of the fetus in vertex
      presentation were: 0.5% neonatal morbidity, 0.2% Apgar scores < 7 at 5 min, 8.1%
      admissions to NICU and 1.5% pH < 7.0 in umbilical arteries. Results comparing
      maternal morbidity in the different breech groups were inconclusive, but there
      were more maternal complications in the breech group planned for VD than in the
      corresponding vertex group (5.1% vs. 1.9%). CONCLUSIONS: Elective CS for breech
      presentation will significantly decrease the risks for the fetus in comparison
      with planned VD.

PMID- 12047310
TI  - The value of routine estradiol monitoring in assisted conception cycles.
AB  - BACKGROUND: Traditional monitoring of an in vitro fertilization (IVF) treatment
      cycle includes regular estradiol levels and ultrasound scans in an attempt to
      reduce the risk of ovarian hyperstimulation syndrome (OHSS). The need for
      estradiol monitoring remains controversial. METHODS: We reviewed 538 consecutive
      cycles of IVF that were carried out in our unit to ascertain whether routine
      estradiol monitoring was of help in preventing OHSS and could be used to predict
      treatment outcome. Two hundred and sixty-eight patients had their ovarian
      response monitored with ultrasound (USS) and estradiol levels on the day of hCG
      administration. The following 270 had USS monitoring but only had an estradiol
      level checked if they were deemed to be at high risk of OHSS (> 20 follicles on
      USS or symptomatic). RESULTS: Pregnancy rates per treatment cycle and per embryo
      transfer were similar in the two groups (all p > 0.05). There were two patients
      in each group requiring admission to hospital for OHSS. CONCLUSIONS: Estradiol
      levels did not correlate with IVF outcome. In summary therefore estradiol levels
      are a poor predictor of treatment success and done routinely do not reduce the
      incidence of OHSS. It is only necessary to measure the estradiol level in those
      patients at risk of OHSS on USS monitoring.

PMID- 12047311
TI  - Ovarian tumor cell detection in peripheral blood progenitor cells harvests by RT
      PCR.
AB  - BACKGROUND: To evaluate the frequency of tumor cell contamination in autologous
      peripheral-blood progenitor cells from patients with ovarian cancer, and to
      determine the impact of infusing such cells on relapses after high-dose
      chemotherapy. METHODS: Seventy-three samples of peripheral-blood progenitor cells
      from 24 ovarian cancer patients were studied for contaminated tumor cells by
      cytokeratin 7 and cytokeratin 20 reverse transcriptase polymerase chain reaction.
      RESULTS: Tumor cell contamination in peripheral-blood progenitor cells was
      detected in 11 of 24 patients (46%) and, among these, in four of 11 patients who
      received transplantations of peripheral-blood progenitor cells. There was no
      trend towards longer relapse-free survival in patients infused with cytokeratin
      negative peripheral-blood progenitor cells as compared with positive ones.
      Interestingly, two of four patients who received transplantations of peripheral
      blood progenitor cells containing tumor cells were free from progression at 20
      and 41 months after transplantation. CONCLUSION: Tumor cell contamination of
      peripheral-blood progenitor cells was frequently noted by transcriptase
      polymerase chain reaction in patients with ovarian cancer. The biological and
      clinical significance of this finding remains to be elucidated.

PMID- 12047312
TI  - Gestational diabetes mellitus and fetal death in Mozambique: an incident case
      referent study.
AB  - BACKGROUND: Third trimester fetal death is a common problem in Mozambique,
      occurring in approximately 5% of parturient women. OBJECTIVE: To elucidate the
      magnitude of the gestational diabetes mellitus problem, and to estimate its
      prevalence in a group of women with unexplained late fetal deaths and in women
      with live fetuses (referents). METHODS: An incident case-referent study of 109
      pregnant Mozambican women with fetal deaths and 110 women delivering liveborns,
      regarding fasting B-glucose, oral glucose tolerance test and glycosylated
      hemoglobin. RESULT: The difference in gestational diabetes mellitus prevalence in
      the two groups is not significant. The prevalence of gestational diabetes
      mellitus was high in both groups: 11% and 7%, respectively.

PMID- 12047313
TI  - Lymphoepithelioma-like carcinoma of the cervix with prominent eosinophilic
      infiltrate: an HPV-18 associated case.

PMID- 12047314
TI  - Vertebral osteomyelitis after abdominal colposacropexy.

PMID- 12047315
TI  - Complete resolution of cervical spinal tuberculosis with paraplegia in pregnancy.

PMID- 12047316
TI  - Pyomyoma after a cesarean section.

PMID- 12047317
TI  - Massive feto-maternal hemorrhage: an early presentation of women with gestational
      choriocarcinoma.

PMID- 12047318
TI  - Scalp metastasis of a serous ovarian cancer.

PMID- 12047319
TI  - Long-term Helicobacter pylori infection in Japanese monkeys induces atrophic
      gastritis and accumulation of mutations in the p53 tumor suppressor gene.
AB  - BACKGROUND: Helicobacter pylori is accepted as a definite human gastric
      carcinogen from an epidemiological point of view despite insufficient
      experimental data. Although we previously showed that the number of p53
      immunopositive cells in the atrophic gastric mucosa of H. pylori-infected
      Japanese monkeys gradually increased over time, data on p53 gene mutations were
      not obtained in that study. To obtain direct evidence of carcinogenesis
      associated with H. pylori infection, we investigated whether p53 gene mutations
      are present in the gastric mucosa of a nonhuman primate model susceptible to H.
      pylori. MATERIALS AND METHODS: Using the DNA from gastric tissues obtained from
      six H. pylori-uninfected monkeys of different ages, nucleotide sequence of the
      wild-type p53 gene was determined by amplification of exons (Ex) 5, 6, 7 and 8
      and sequencing. Gastric specimens obtained from eight Japanese monkeys that had
      been infected with H. pylori for different lengths of time (1.5-7.5 years), were
      analyzed for mutations in exons 5-8 of p53. RESULTS: In the six H. pylori
      uninfected monkeys, nucleotide sequences of p53 Ex 5-8 were completely common and
      no mutations were noted. However, among the monkeys that were infected with H.
      pylori over various periods of time, there was an accumulation of p53 nucleotide
      (amino acid) substitutions as the gastric atrophy score increased. CONCLUSIONS:
      We conclude that the appearance of p53 gene mutation may be closely associated
      with the degree of gastric mucosal atrophy, which depends on the duration of H.
      pylori infection. Searching for p53 gene mutations may be useful for studying the
      progression of gastric carcinogenesis associated with H. pylori.

PMID- 12047320
TI  - Enhanced expression of transcription factor E2F in Helicobacter pylori-infected
      gastric mucosa.
AB  - OBJECTIVE: Helicobacter pylori is implicated in gastric carcinogenesis through
      increased gastric epithelial cell turnover. In fact, high proportions of
      proliferating and apoptotic epithelial cells are found in H. pylori-infected
      gastric mucosa. E2F, a transcription factor, induces coordinated transactivation
      of a set of genes involved in cell cycle progression. The aim of this study was
      to investigate the expression of E2F in H. pylori-infected gastric mucosa and
      examine the correlation between such expression and gastric epithelial cell
      proliferation and apoptosis. METHODS: Twenty-five patients with H. pylori
      associated gastritis (HAG) and 13 control subjects negative for H. pylori were
      examined. E2F expression was studied in situ by Southwestern histochemistry, a
      method used to localize transcription factors. Labeled double-stranded oligo-DNA
      with specific consensus sequence for E2F binding sites was reacted with frozen
      sections from antral biopsy specimens obtained at endoscopy. Gastric epithelial
      cell proliferation was assessed by immunostaining of proliferating cell nuclear
      antigen (PCNA), while apoptosis was detected by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL). The percentages of
      epithelial cells with nuclear staining for PCNA and E2F were expressed as a
      positivity index (PI). The percentage of TUNEL-positive epithelial cells was
      defined as apoptotic index. RESULTS: E2F was expressed in the nuclei of gastric
      epithelial cells within gastric pits. E2F PI in H. pylori-infected gastric mucosa
      was significantly higher than that in noninfected. Expression of E2F correlated
      well with PCNA-positive epithelial cells. We also demonstrated colocalization of
      PCNA with E2F expression in the same epithelial cells. Apoptotic index was also
      high in H. pylori-infected mucosa, and correlated with E2F PI. CONCLUSION: Our
      results demonstrated a significant increase in the expression of E2F in H. pylori
      infected mucosa, which correlated with both the percentages of PCNA- and TUNEL
      positive cells. Our results suggest that enhanced E2F expression in gastric
      mucosa may be involved in H. pylori-related gastric carcinogenesis through
      accelerated cell turnover.

PMID- 12047321
TI  - Helicobacter pylori does not mediate the formation of carcinogenic N
      nitrosamines.
AB  - BACKGROUND: Both N-nitroso compounds and colonization with Helicobacter pylori
      represent known risk-factors for the development of gastric cancer. Endogenous
      formation of N-nitroso compounds is thought to occur predominantly in acidic
      environments such as the stomach. At neutral pH, bacteria can catalyze the
      formation of N-nitroso compounds. Based on experiments with a noncarcinogenic N
      nitroso compound as end product, and using only a single H. pylori strain, it was
      recently reported that H. pylori only displays a low nitrosation capacity. As H.
      pylori is a highly diverse bacterial species, it is reasonable to question the
      generality of this finding. In this study, several genetically distinct H. pylori
      strains are tested for their capacity to form carcinogenic N-nitrosamines.
      MATERIALS AND METHODS: Bacteria were grown in the presence of 0-1000 microM
      morpholine and nitrite (in a 1 : 1 molar ratio), at pH 7, 5 and 3. RESULTS:
      Incubation of Neisseria cinerea (positive control) with 500 microM morpholine and
      500 microM nitrite, resulted in a significant increase in formation of N
      nitrosomorpholine, but there was no significant induction of N-nitrosomorpholine
      formation by any of the H. pylori strains, at any of the three pH conditions.
      CONCLUSION: H. pylori does not induce formation of the carcinogenic N
      nitrosomorpholine in vitro. The previously reported weak nitrosation capacity of
      H. pylori is not sufficient to nitrosate the more difficulty nitrosatable
      morpholine. This probably also holds true for other secondary amines. These
      results imply that the increased incidence of gastric cancer formation that is
      associated with gastric colonization by H. pylori is unlikely to result from the
      direct induced formation of carcinogenic nitrosamines by H. pylori. However, this
      has to be further confirmed in in vivo studies.

PMID- 12047322
TI  - Production of chemokines and reactive oxygen species by human neutrophils
      stimulated by Helicobacter pylori.
AB  - BACKGROUND: Bacteria have different characteristics in stimulation of human
      neutrophils to produce reactive oxygen species (ROS) and chemokines. This study
      examined the ability of Helicobacter pylori to induce production of ROS and
      chemokines by human neutrophils. METHODS: H. pylori strains (1.5 x 108 CFU/ml)
      were cocultured with 5 x 104 neutrophils isolated from healthy subjects. Samples
      were incubated with human serum with or without IgG antibodies to H. pylori. ROS
      production was measured using luminol-dependent chemiluminescence (LmCL), and the
      concentrations of chemokines (IL-8, RANTES, MIP-1alpha and MCP-1) were measured
      by ELISA. RESULTS: The mean of the highest LmCL (peak height; PH) value
      stimulated by H. pylori was 3318 in the absence of serum. PH increased to 4687
      when incubated with anti-H. pylori antibody-positive sera (p <.001) but antibody
      negative sera did not affect LmCL response. The mean final concentration of IL-8
      produced in the absence of serum was 142.6 pg/ml. Increased IL-8 production was
      seen by addition of antibody positive serum (p <.01). IL-8 production was not
      significantly correlated with production of ROS. On the other hand, H. pylori
      stimulation did not induce neutrophil production of RANTES, MIP-1alpha or MCP-1.
      CONCLUSIONS: H. pylori was capable of inducing IL-8 production by human
      neutrophils, but not C-C chemokines. Production of C-X-C dominant chemokine by
      neutrophils is consistent with the pathological characteristics of H. pylori
      induced gastritis, where persistent neutrophil infiltration is present.

PMID- 12047323
TI  - Proteome analysis of highly immunoreactive proteins of Helicobacter pylori.
AB  - BACKGROUND: Identification of the immunoreactive proteins of Helicobacter pylori
      is important for the development of both diagnostic tests and vaccines relating
      to the organism. Our aim was to determine whether there are significant
      differences between human IgG and IgA reactivities to individual H. pylori
      proteins, and whether patterns of immunoreactivity are sustained across different
      strains of H. pylori. METHOD: The total complement of protein from seven strains
      of H. pylori was resolved by two-dimensional polyacrylamide gel electrophoresis
      (2D-PAGE). Proteins were transferred electrophoretically onto polyvinylene
      difluoride (PVDF) membranes, which were probed with sera pooled either from H.
      pylori-infected patients, or noninfected (control) patients. Highly
      immunoreactive proteins were detected using chromogenic enzyme-antibody
      conjugates recognising either serum IgG or IgA. These proteins were then
      characterised by tryptic peptide-mass fingerprinting using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS:
      Highly immunoreactive proteins were detected which were common to all seven
      strains, and recognised by both immunoglobulin subclasses. The proteins appear to
      be localised in five groups. Protein analysis established that these groups
      encompass multiple isoforms of chaperonin HspB (two subgroups); urease beta
      subunit UreB; elongation factor EF-Tu; and flagellin FlaA. The pattern of highly
      immunoreactive proteins was strongly conserved across the seven strains.
      CONCLUSION: These results suggest that within a tightly defined region on the H.
      pylori proteome map there are five groups of proteins that are highly reactive to
      both IgG and IgA. Our analysis suggests it is unlikely that the highly
      immunoreactive clusters harbour any significant proteins other than isoforms of
      HspB, UreB, EF-Tu and FlaA, and that, with the partial exception of FlaA, these
      clusters are strongly conserved across all seven strains.

PMID- 12047324
TI  - Additive effect of pronase on the efficacy of eradication therapy against
      Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori (H. pylori) colonizes not only the surface of the
      surface mucous cells but also the surface mucous gel layer (SMGL). Thus, we
      examined the possible value of pronase, a mucolytic agent, as a potential
      eradication therapy. MATERIALS AND METHODS: One hundred and thirty-five patients
      were randomly assigned to two treatment groups. Sixty-eight patients received 30
      mg of lansoprazole once daily, 500 mg of amoxicillin and 250 mg of metronidazole
      thrice daily for 2 weeks (LAM group), while the other 67 patients received the
      same dosage of those agents plus 18,000 tyrosine units of pronase thrice daily
      for 2 weeks (LAMP group). Eradication was assessed 4-6 weeks after treatment by
      immunohistochemical tests and cultures. We also determined the in vitro activity
      of pronase against H. pylori, and evaluated the synergistic effects between
      pronase and the other three drugs. To investigate the effect of pronase on the
      structure of the SMGL, surgically removed stomachs obtained from patients who had
      taken pronase were examined histopathologically. RESULTS: The cure rates for H.
      pylori infection in the LAMP group were significantly higher than those in the
      LAM group (intention to treat analysis: 94.0 vs. 76.5%, p =.0041). Pronase
      exhibited no antibacterial activity against H. pylori., and no in vitro
      synergistic effects were observed. In the patients who took pronase before
      surgery, the SMGL was thinner than in the patients who did not take pronase, and
      the structure of the SMGL was markedly disrupted. CONCLUSIONS: Pronase has an
      additive effect in curing H. pylori infection. Pronase has no apparent in vitro
      activity against H. pylori, but may improve the local delivery of antibiotics by
      virtue of its removal and disruption of the SMGL.

PMID- 12047325
TI  - Aberrant expression of CDX2 in the gastric mucosa with and without intestinal
      metaplasia: effect of eradication of Helicobacter pylori.
AB  - BACKGROUND: The intestine-specific transcription factor CDX2 plays an important
      role in differentiation and maintenance of intestinal epithelial cells.
      Development and progression of intestinal metaplasia (IM) in the stomach is
      closely associated with Helicobacter pylori-gastritis. We investigated expression
      of CDX2 protein in the gastric mucosa with and without IM before and after
      eradication of H. pylori. MATERIALS AND METHODS: The subjects comprised five
      normal controls and 29 H. pylori-positive patients (15 with antral IM and 14
      without IM), who were followed for 12 months after eradication of H. pylori.
      Biopsies were taken from the greater curvatures of the antrum and middle body.
      Expression of CDX2 was evaluated immunohistochemically using anti-CDX2 antibody.
      RESULTS: CDX2 expression was not found in controls. Strong nuclear staining was
      observed extensively in IM, but rarely in the gastric epithelium, except for the
      focal area in only four antral biopsies (three with and one without IM). Fine
      granular cytoplasmic staining was also observed in the perinuclear regions of IM
      and the gastric epithelial cells in half of the patients. In 13 of the 15
      patients with IM, IM did not regress after eradication of H. pylori, and the
      extent of nuclear staining in IM did not change. The extent of cytoplasmic
      staining did not change either. CONCLUSIONS: Our results indicate that CDX2
      expression in the gastric mucosa is found in patients with chronic gastritis and
      is closely associated with IM. CDX2 expression in IM or the gastric epithelial
      cells did not disappear after eradication of H. pylori.

PMID- 12047326
TI  - Stool antigen assay to screen H. pylori infection and to assess the success of 3
      Day and 7-Day eradication therapy in the patients with partial gastrectomy.
AB  - BACKGROUND: Even after partial gastrectomy, Helicobacter pylori may persist in
      the residual stomach but be less abundant in the bacterial load. H. pylori stool
      antigen is a reliable noninvasive tool to detect H. pylori infection in patients
      without gastrectomy. We thus test whether [1] the course of H. pylori eradication
      therapy could be diminished [2]; stool antigen can effectively detect H. pylori
      infection for the patients with gastrectomy. METHODS: One hundred and eight
      patients who had undergone partial gastrectomy were enrolled to receive
      panendoscopy and provided stool samples for H. pylori stool antigen within 3 days
      after endoscopy. The H. pylori-infected patients were then randomized to receive
      either a 3- or 7-day triple therapy for H. pylori eradication. Six weeks later,
      to evaluate the success of H. pylori eradication, patients received a follow-up
      endoscopy and again provided stool samples for H. pylori stool antigen. RESULTS:
      Seventy out of 108 patients, proven to have H. pylori infection, were evenly
      randomized into 3-day and 7-day therapy groups. The H. pylori eradication rates
      were similar between the 3-day and 7-day triple therapy (90.9 vs. 93.8%, p >.05).
      Before therapy, the H. pylori stool antigen was 93% sensitive and 100% specific
      to detect H. pylori. After therapy, H. pylori stool antigen remain 100% sensitive
      and 88.3% specific to detect the failure of eradication therapy. CONCLUSION: H.
      pylori stool antigen is a highly reliable tool to screen H. pylori infection
      before therapy and to assess the success of eradication therapy in partial
      gastrectomy patients. To eradicate H. pylori infection for patients with partial
      gastrectomy, the duration of triple therapy can be shortened.

PMID- 12047327
TI  - Accuracy of office-based immunoassays for the diagnosis of Helicobacter pylori
      infection in children.
AB  - BACKGROUND: Rapid non-invasive diagnostic tests that can reliably document the
      presence or absence of Helicobacter pylori infection are urgently required. The
      aim of this study was to determine the accuracy of two immunoassays (Flex-Sure
      and MedMira), developed for use outside the laboratory setting by practitioners,
      in the setting of a low prevalence of H. pylori infection. METHODS: Serum samples
      collected in four previous studies (n = 349) were employed to detect the presence
      of H. pylori-specific immunoglobulin G, compared to previous results obtained
      using endoscopic biopsies, serology, flow cytometry, and urease breath testing.
      Serum samples included 52 obtained from adults (parents and grandparents of
      symptomatic children), 123 sera collected from children and adolescents
      undergoing diagnostic upper endoscopy for upper gastrointestinal tract symptoms,
      and 174 samples drawn from children in the primary care setting with or without
      recurrent abdominal pain. RESULTS: Overall, 16% of subjects were infected by the
      gastric pathogen. Both the specificity (%) and negative predictive value (%) of
      the two tests were high (FlexSure: 91 and 92; Medmira: 97 and 94, respectively).
      In adults, both tests also demonstrated high sensitivity (83% and 86%) and
      positive predictive values (79% and 83%, respectively). However, in children
      where the prevalence of infection was 12% (37 of 297 subjects), the sensitivity
      (59% and 71%) and positive predictive values (55% and 88%, respectively) of the
      immunoassays were lower. CONCLUSIONS: These findings indicate that, in the
      setting of a low prevalence of H. pylori infection, the MedMira office-based test
      provides satisfactory results and utility. However, the low positive-predictive
      value of the FlexSure kit may limit applicability of this test in children.

PMID- 12047328
TI  - Evaluation of a Western blot test, Helico blot 2.1, in the diagnosis of
      Helicobacter pylori infection in a pediatric population.
AB  - BACKGROUND: Noninvasive diagnostic tests are useful as screening tools for
      Helicobacter pylori infection in pediatric populations. The aim of this study was
      to evaluate performance of the immunoblot assay, Helico Blot 2.1, for the
      diagnosis of H. pylori infection in symptomatic children. MATERIALS AND METHODS:
      Immunoblot assay was used for detection of IgG antibodies to specific H. pylori
      proteins and to a recombinant H. pylori antigen, CIM marker. The study was
      performed on sera collected from 134 symptomatic, untreated children (mean age,
      9.1 +/- 3.2 years; range, 1-14 years). H. pylori infection status was determined
      by culture, histology and rapid urease test. RESULTS: Immunoblot assay yielded a
      positive result in 71 of the 72 infected patients (sensitivity 98.6%) and in
      eight of the 62 noninfected ones (specificity 87.1%). The predictive values for a
      positive and a negative result were 89.9% and 98.2%, respectively. The
      performance of the CIM band alone, as a marker for H. pylori infection status,
      was also evaluated. This band was present on the blot of 71 infected patients and
      on four of the 62 H. pylori-negative patients. The sensitivity, specificity, PPV
      and NPV of the CIM antigen were 98.6%, 93.5%, 94.7% and 98.3%, respectively.
      CONCLUSIONS: The immunoblot assay Helico Blot 2.1 is a suitable noninvasive test
      for the serodiagnosis of H. pylori infection in children. The good level of
      performance demonstrated by the novel recombinant antigen CIM suggests it may be
      a useful contribution to the qualitative and quantitative performance of the
      Helico Blot 2.1 in pediatric populations.

PMID- 12047329
TI  - Costs of managing Helicobacter pylori-infected ulcer patients after initial
      therapy.

PMID- 12047331
TI  - Migraine without aura and migraine with aura are distinct disorders. A population
      based twin survey.
AB  - OBJECTIVE: To investigate the co-occurrence of migraine without aura (MWOA) and
      migraine with aura (MWA) in a population-based twin survey. BACKGROUND: Migraine
      without aura and MWA are multifactorial disorders. If MWOA and MWA share common
      genes, co-occurrence should be observed more frequently than expected, ie, the
      product of the prevalence in the general population. MATERIAL AND METHODS: The
      study population included all living Danish monozygotic (MZ) and same-gender
      dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334
      DZ). The sample included 2840 men and 2520 women. All received a posted
      questionnaire, and those with possible migraine were interviewed via telephone by
      trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire
      and who had a co-twin with possible migraine were contacted by telephone. The
      questionnaire response rate was 87% (4660 of 5360), and the telephone interview
      was participated in by 90% (2035 of 2272). The physician interviewers were
      unaware of questionnaire answers, zygosity, and the clinical diagnosis of the co
      twin. The criteria of the International Headache Society were used to establish a
      diagnosis of migraine. RESULTS: Lifetime prevalence in the twin sample: 7% of men
      and 19% of women had MWOA, while 7% of men and 8% of women had MWA. Lifetime
      prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ women, 6% (5
      of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182). Lifetime prevalence
      of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ women, 5% (3 of 58); DZ
      men, 9% (4 of 44); and DZ women, 13% (10 of 76). The observed and the expected
      numbers of twins with co-occurrence of MWOA and MWA based on the prevalence in
      the general population were not significantly different in either men or women
      (men, P=.1 and women, P=.5). CONCLUSION: The results strongly suggest that MWOA
      and MWA are distinct disorders, and identification of common genes for MWOA and
      MWA, thus, should not be expected to result from future genetic research.

PMID- 12047333
TI  - Tumor necrosis factor gene polymorphism in migraine.
AB  - OBJECTIVE: To better define the involvement of human leukocyte antigen region
      (HLA) genes in migraine via an association study of the tumor necrosis factor
      (TNF) genes, located in the HLA class III region, with migraine with and without
      aura. BACKGROUND: Migraine without aura and migraine with aura are disorders
      involving multiple factors-environmental and genetic. In a previous study, we
      hypothesized a protective role for the HLA-DR2 antigen, providing additional
      basis for the proposed genetic heterogeneity between migraine without aura and
      migraine with aura. The cytokines produced by TNF genes are polypeptide effectors
      of inflammatory reaction and endothelial function. METHODS: Tumor necrosis factor
      (TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and
      TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain
      reaction-amplified fragments in 47 patients with migraine without aura, 32
      patients with migraine with aura, and 101 migraine-free controls. RESULTS: The
      frequency of TNFB*2 allele was significantly increased in our patients with
      migraine without aura as compared with the control group (78.72% versus 61.4%, Pc
      =.004), but no significant differences were found between patients with migraine
      with aura and controls. Additionally, there was a significant decrease of TNFB*1
      homozygotes in patients with migraine without aura compared with the control
      group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a
      high risk for the development of migraine without aura. No significant
      association was found at TNF-308 polymorphism. CONCLUSION: These data support the
      hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine
      without aura and confirm previous data indicating that migraine with and without
      aura are distinct entities with different genetic backgrounds.

PMID- 12047334
TI  - Dopamine receptor genes and migraine with and without aura: an association study.
AB  - OBJECTIVE: To investigate the role of the dopamine receptor genes, DRD1, DRD3,
      and DRD5 in the pathogenesis of migraine. BACKGROUND: Migraine is a chronic
      debilitating disorder affecting approximately 12% of the white population. The
      disease shows strong familial aggregation and presumably has a genetic basis, but
      at present, the type and number of genes involved is unclear. The study of
      candidate genes can prove useful in the identification of genes involved in
      complex diseases such as migraine, especially if the contribution of the gene to
      phenotypic expression is minor. Genes coding for proteins involved in dopamine
      metabolism have been implicated in a number of neurologic conditions and may play
      a contributory role in migraine. Hence, genes that code for enzymes and receptors
      modulating dopaminergic activity are good candidates for investigation of the
      molecular genetic basis of migraine. METHODS: We tested 275 migraineurs and 275
      age- and sex-matched individuals free of migraine. Genotypic results were
      determined by restriction endonuclease digestion of polymerase chain reaction
      products to detect DRD1 and DRD3 alleles and by Genescan analysis after
      polymerase chain reaction using fluorescently labelled oligonucleotide primers
      for the DRD5 marker. RESULTS: Results of chi-square statistical analyses
      indicated that the allele distribution for migraine cases compared to controls
      was not significantly different for any of the three tested gene markers (chi2 =
      0.1, P =.74 for DRD1; chi2 = 1.8, P =.18 for DRD3; and chi2 = 20.3, P =.08 for
      DRD5). CONCLUSIONS: These findings offer no evidence for allelic association
      between the tested dopamine receptor gene polymorphisms and the more prevalent
      forms of migraine and, therefore, do not support a role for these genes in the
      pathogenesis of the disorder.

PMID- 12047332
TI  - A polymorphism in the interleukin-1alpha gene influences the clinical features of
      migraine.
AB  - OBJECTIVE: To evaluate whether a particular genotype of the interleukin-1alpha
      (IL1A) gene affects the clinical features of migraine. BACKGROUND:
      Proinflammatory mediators have been reported to play a role in the
      pathophysiology of migraine. Recent studies suggest that polymorphisms in the
      interleukin-1 genes influence the age at onset and subsequent course of several
      chronic inflammatory diseases. METHODS: In a group of 269 patients with migraine,
      we tested the association of the -889 C/T biallelic polymorphism of the IL1A gene
      with several clinical features of the disease. RESULTS: Patients with migraine
      carrying the T/T genotype show an age at onset of the disease that is
      significantly (P <.01) lower than IL1A C/C or C/T carriers. In addition, the same
      genotype was significantly (P <.05) more frequent in patients with migraine with
      aura than in patients with migraine without aura. CONCLUSIONS: The results of our
      study suggest a role for the IL1A gene in modifying the clinical features of
      migraine.

PMID- 12047335
TI  - Livedo reticularis and migraine: a marker for stroke risk?
AB  - BACKGROUND AND PURPOSE: Livedo reticularis is a dermatopathy characterized by an
      irregular, violaceous, netlike pattern which spares the face. Associated with a
      variety of conditions, it occurs consequent to pathological or physiological
      narrowing of small and medium arteries at the dermis-subcutis border. Sneddon
      syndrome refers to the idiopathic coupling of livedo reticularis and stroke in
      the absence of traditional vascular risk factors. Over 50% of persons with
      Sneddon syndrome describe a history of headache. We undertook this study to
      determine the frequency of livedo reticularis in our headache clinic. METHODS: We
      performed a retrospective chart review of consecutive patients attending a
      headache clinic over a period of 6 months. The patients had all been seen by one
      physician (G.E.T.) who noted the presence or absence of livedo reticularis. The
      charts were reviewed for age, sex, and vascular risk factors, including current
      use of oral contraceptives, and history of smoking, coronary artery disease,
      hypertension, diabetes mellitus, stroke, or arthritis. RESULTS: Charts from 133
      patients with headache were reviewed (24 men [18%], 109 women [82%]; mean age, 42
      +/- 13 years). Livedo reticularis was observed in 29 patients (22%) and in a
      similar proportion in men (25%) and women (21%). When we stratified the migraine
      population by presence or absence of livedo, we found no significant difference
      in age (44.5 versus 41.7 years, P =.16). There was a higher frequency of stroke
      diagnosis in the cohort with livedo reticularis (28%[8 of 29] versus 7%[7 of
      104], P =.005), but we found no significant differences in frequency of
      hypertension, oral contraceptive use, diabetes mellitus, coronary artery disease,
      arthritis, or cigarette smoking. CONCLUSIONS: In our headache clinic, livedo
      reticularis is present in more than one fifth of patients. A history of stroke is
      more frequent in this subset of migraineurs, raising the possibility that livedo
      reticularis can be used as a clinical marker to identify those migraineurs with
      an increased risk of stroke.

PMID- 12047336
TI  - Disappearance of migraine attacks during long-lasting postdural puncture
      headache: a case report.
AB  - We report a patient with a history of frequent migraine attacks who developed
      postdural puncture headache that persisted for 3 months. His migraine attacks
      ceased during the period of his postdural puncture headache, but resumed 3 days
      after disappearance of that headache. This case suggests an interrelationship
      between the mechanisms of postdural puncture headache and migraine.

PMID- 12047337
TI  - Spontaneous intracranial hypotension: quick clinical and magnetic resonance
      imaging response to corticosteroids. A case report.

PMID- 12047338
TI  - Headache with prolonged focal neurologic symptoms and cerebrospinal fluid
      pleocytosis: a case report.

PMID- 12047339
TI  - Genetics of migraine: possible links to neurophysiological abnormalities.

PMID- 12047340
TI  - Sympathetic look at genetic basis of migraine.

PMID- 12047341
TI  - A rare cause of cough headache in an adult.

PMID- 12047342
TI  - Management of basilar migraine.

PMID- 12047343
TI  - High prevalence of antiendothelial cell antibodies in migraine.

PMID- 12047344
TI  - Stadol nasal spray for headache.

PMID- 12047345
TI  - A temporal approach to headache.

PMID- 12047346
TI  - The sky is falling: head injuries in warehouse retail stores.

PMID- 12047348
TI  - Circadian rhythm of aromatic L-amino acid decarboxylase in the rat
      suprachiasmatic nucleus: gene expression and decarboxylating activity in clock
      oscillating cells.
AB  - BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible
      for the decarboxylation step in both the catecholamine and indoleamine synthetic
      pathways. In the brain, however, a group of AADC containing neurones is found
      outside the classical monoaminergic cell groups. Since such non-monoaminergic
      AADC is expressed abundantly in the suprachiasmatic nucleus (SCN), the mammalian
      circadian centre, we characterized the role of AADC in circadian oscillation.
      RESULTS: AADC gene expression was observed in neurones of the dorsomedial
      subdivision of the SCN and its dorsal continuant in the anterior hypothalamic
      area. These AADC neurones could uptake exogenously applied L-DOPA and formed
      dopamine. AADC was co-expressed with vasopressin and the clock gene Per1 in the
      neurones of the SCN. Circadian gene expression of AADC was observed with a peak
      at subjective day and a trough at subjective night. The circadian rhythm of AADC
      enzyme activity in the SCN reflects the expression of the gene. CONCLUSIONS: Non
      monoaminergic AADC in the SCN is expressed in clock oscillating cells, and the
      decarboxylating activity of master clock cells are under the control of the
      circadian rhythm.

PMID- 12047349
TI  - ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of
      epithelial cells.
AB  - BACKGROUND: ERBIN, an ErbB2 receptor-interacting protein, belongs to a recently
      described family of proteins termed the LAP [leucine-rich repeats and PSD-95/dLg
      A/ZO-1 (PDZ) domains] family which has essential roles in establishment of cell
      polarity. RESULTS: To identify new ERBIN-binding proteins, we screened a yeast
      two-hybrid library, using the carboxyl-terminal fragment of ERBIN containing PDZ
      domain as the bait, and we isolated p0071 (also called plakophilin-4) as an ERBIN
      interacting protein. p0071 is a member of the p120 catenin family, which are
      defined as proteins with 10 armadillo repeats, and localizes along the cell-cell
      border. The ERBIN PDZ domain binds the COOH-terminus of p0071 containing the PDZ
      domain-binding sequence. Endogenous ERBIN was co-immunoprecipitated with p0071.
      In fully polarized Madin-Darby canine kidney (MDCK) cells, ERBIN co-localized
      largely with beta-catenin and partly with desmoplakin along the lateral plasma
      membrane domain. At these cell-cell contact regions, ERBIN co-localizes with
      p0071. Over-expression of the dominant active forms of Cdc42, Rac1 or RhoA, Rho
      family small GTPases, resulted in a marked accumulation of ERBIN at the cell-cell
      contacts of MDCK and HeLa cells. CONCLUSION: These results show that ERBIN
      interacts in vivo with p0071 and that it may be involved in the organization of
      adherens junctions and the desmosomes of epithelia. In addition, we demonstrated
      that the subcellular localization of ERBIN might be regulated by Rho family small
      GTPases.

PMID- 12047350
TI  - Involvement of NLK and Sox11 in neural induction in Xenopus development.
AB  - BACKGROUND: The Wnt signal transduction pathway regulates various aspects of
      embryonal development and has been implicated in promoting cancer. Signalling by
      Wnts leads to the stabilization of cytosolic beta-catenin, which then associates
      with TCF transcription factors to regulate expression of Wnt-target genes. The
      Wnt pathway is further subject to cross-regulation at various levels by other
      components. RESULTS: Recent evidence suggests that a specific MAP kinase pathway
      involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt
      signalling. In particular, it has been shown that TAK1 activates NLK, which
      phosphorylates TCFs bound to beta-catenin. This phosphorylation down-regulates
      the DNA-binding activity of a TCF-4/beta-catenin complex, and blocks activation
      of their target genes. To investigate the role of NLK in Xenopus development, we
      isolated xNLK, a Xenopus homologue of NLK. Our findings indicate that xNLK is
      expressed in neural tissues and induces the anterior-neural marker gene, Otx-2.
      Moreover, xSox11, which is induced by the expression of Chordin, co-operates with
      xNLK to induce neural development. These molecules also interact in mammalian
      cells, and expression of a mutant of xNLK lacking kinase activity was found to
      suppress the induction of neural marker gene expression by xSox11. CONCLUSIONS:
      Our findings indicate that xNLK may play a role in neural development together
      with xSox11 during early Xenopus embryogenesis.

PMID- 12047351
TI  - Genome-wide analysis of changes in early gene expression induced by oestrogen.
AB  - BACKGROUND: The sex hormone 17beta-oestradiol (E2) has profound effects on many
      aspects of reproduction, development, as well as behaviour. Although the
      oestrogen receptor is well characterized on a molecular level, relatively few
      genes affected by E2 have been identified, and the mechanisms underlying the
      physiological changes caused by E2 are largely unknown. In order to identify
      oestrogen-regulated genes in vivo, early uterine gene expression profiles were
      developed using DNA microarrays. RESULTS: Ovariectomized mice were exposed to
      17beta-oestradiol for 6 h, and mRNA expression analysis for 9977 genes was
      performed. Although a large number of genes was affected by oestrogen
      administration, the genes that showed higher reproducibility in repetitive
      experiments were selected and further examined. For most of the selected genes,
      expression was induced in a dose-dependent manner, and gene expression was not
      altered following oestrogen treatment in oestrogen receptor-alpha (ER(alpha))
      deficient mice. In combination with the estimation of gene expression levels
      using quantitative PCR, it was revealed that multiple genes related to sterol
      biosynthesis, tRNA synthesis, RNA processing, and growth signalling were
      activated. Based on the microarray data, we selected additional genes related to
      sterol biosynthesis and tRNA synthesis and confirmed that these genes are also
      activated by oestrogen. CONCLUSION: Genes suggesting a basis for the drastic
      uterotrophic effect observed several days following oestrogen administration were
      identified. These findings not only reveal the diverse effect of oestrogen
      signalling on transcript levels in vivo but also demonstrate the ability of DNA
      microarrays to identify cellular pathways affected by oestrogen.

PMID- 12047354
TI  - Rapid and simultaneous HLA class I (-A, -B and -C loci) DNA typing using the
      microtitre plate-reverse hybridization assay (MRHA).
AB  - We have established a precise, rapid, simple and practical HLA class I DNA typing
      method using the microtitre plate-reverse hybridization assay (MRHA), which
      enables us to perform simultaneous DNA typing of the HLA-A, -B and -C loci using
      the same PCR parameters and hybridization conditions. PCR-amplified products for
      the HLA-A, -B and -C loci were hybridized, respectively, with sequence-specific
      oligonucleotide (SSO) probes, which were immobilized covalently onto a microtitre
      plate, in hybridization buffer containing formamide at 37 degrees C. After
      washing at room temperature, the bound PCR products were detected by peroxidase
      conjugate streptavidine followed by colour development such as enzyme immunoassay
      (EIA). In addition to the simple thermoregulation for hybridization and
      postwashing, strong positive signals, low background and high reproducibility,
      this DNA typing method enabled simultaneous typing of the HLA-A, -B and -C loci
      using a single microtitre plate as in HLA serotyping. The assignment of the HLA
      genotype was easily achieved by automated colorimetric reading and computer
      software, based on the cut-off value (threshold) established for each probe. For
      routine HLA class I typing, it may be possible to replace serological typing with
      the HLA class I DNA typing system using our MRHA method.

PMID- 12047352
TI  - Bacterial SsrA system plays a role in coping with unwanted translational
      readthrough caused by suppressor tRNAs.
AB  - BACKGROUND: Bacterial SsrA RNA (also known as tmRNA or 10Sa RNA) mediates the
      addition of a short peptide tag to the C-terminus of the nascent polypeptide when
      a ribosome is stalled at the 3' end of an mRNA lacking a stop codon. This
      process, called trans-translation, rescues the stalled ribosome and ensures
      degradation of tagged polypeptides by ATP-dependent proteases. To fully
      understand the physiological roles of SsrA RNA, it is essential to know how
      endogenous mRNA targets for the SsrA system are generated in cells. The aim of
      the present study is to examine how translational readthrough by suppressor tRNAs
      affects trans-translation in Escherichia coli. RESULTS: We demonstrated that SsrA
      tagging of bulk cellular proteins was significantly enhanced by an ochre or an
      amber suppressor tRNA. Western blot analysis of proteins produced from specific
      genes possessing a Rho-independent terminator revealed that readthrough at the
      normal stop codon leads to an efficient tagging and proteolysis of the extended
      proteins. Size analyses of both protein and mRNA suggested that tagging of
      extended proteins occurs because ribosome passing through the normal stop codon
      presumably reach the 3' end of mRNA defined by the transcription terminator
      hairpin. The inhibitory effect of ssrA mutation on cell growth was markedly
      amplified in cells with an ochre suppressor tRNA. CONCLUSION: The present finding
      suggests that the SsrA system contributes to scavenge errors and/or problems
      caused by translational readthrough that occurs typically in the presence of a
      suppressor tRNA.

PMID- 12047355
TI  - HLA class I polymorphism in a Moroccan population from Casablanca.
AB  - We have studied the distribution of HLA-A and -B alleles and haplotypes by
      sequence-specific primer amplification in a sample of 100 unrelated healthy
      individuals belonging to both Berber and Arabic-speaking groups from the region
      of Casablanca in Morocco. Among the 17 HLA-A and 23 HLA-B alleles observed, the
      most frequent were HLA-A2 (21%), -A1 (11%), -A3 (10%), -B44 (11.4%), -B50 (9.9%),
      -B5(8.5%) and -B35 (6.5%). Six two-locus haplotypes were observed with a
      frequency above 5%: A2-B50 (9.6%), A23-B44 (7.4%), A2-B15 (6.4%), A68-B39 (5.3%),
      A1-B51 (5.3%) and A68-B44 (4.3%). Our data confirm that, on the basis of genetic
      distances, the majority of present-day North Africans from Morocco are closely
      related to Berbers and also to Iberians. They cluster apart from Middle-Eastern
      Mediterranean populations, and show greater genetic distances to Eastern and
      other Mediterranean populations. This study will serve as a reference for further
      anthropological studies, as well as studies of HLA and disease associations.

PMID- 12047356
TI  - Characterization of Peromyscus MHC class II beta sequences by ligation-anchored
      RT-PCR and denaturing gradient gel electrophoresis.
AB  - We characterized MHC class II beta sequences in deermice (genus Peromyscus),
      which are amongst the most common mammals in North America. We find evidence for
      two different families of class II beta loci, most closely related to either the
      A-type or E-type loci in Mus. Population studies suggest the presence of more
      than one A-type locus but only one E-type locus for the species investigated.

PMID- 12047357
TI  - The CTLA4 +49 A/G dimorphism is not associated with type 1 diabetes in Czech
      children.
AB  - We investigated the association of the CTLA4 +49 A/G dimorphism with type 1
      diabetes in Czech children. Genotyping of 305 diabetic children and 289 controls
      by a novel PCR-ARMS assay revealed no significant differences in the genotypic or
      allelic frequencies. This may be another piece of evidence against the +49 A/G
      transition as the aetiological polymorphism within the CTLA4 gene.

PMID- 12047358
TI  - Distribution of bovine lymphocyte antigen (BoLA-DRB3) alleles in Brazilian dairy
      Gir cattle (Bos indicus).
AB  - Brazilian dairy Gir (Bos indicus) cattle are a tropical, well-adapted breed, for
      which no information on the major histocompatibility complex (MHC) is presently
      available. The second exon of the bovine lymphocyte antigen (BoLA-DRB3) was
      amplified by polymerase chain reaction (PCR) of DNA samples from 28 Brazilian
      dairy Gir cows. Two experimental genotyping approaches were used: direct
      sequencing of PCR gene products (PCR-DS) and sequencing of cloned PCR fragments
      (S-CLO). Results demonstrate the viability of both typing approaches. PCR-DS
      allowed typing of 39% of the animals while the remainder were genotyped by S-CLO.
      Seventeen BoLA-DRB3 alleles were assigned, including some that were only recently
      described for zebu cattle. Allelic frequencies ranged from 0.02 to 0.18. The most
      frequent alleles were *3601 (frequency = 0.18), *2201 (0.14) and *2101 (0.11).

PMID- 12047359
TI  - Sequence similarity matching: proposal of a structure-based rating system for
      bone marrow transplantation.
AB  - Recent advances in DNA-based typing have led to the detection of a continuously
      growing number of HLA alleles. For this reason, HLA matching in transplantation
      of hematopoietic stem cells from unrelated donors has become increasingly
      complicated. When there is no genotypically identical sibling and there are
      several alternative potential donors that all have a mismatch at a relevant HLA
      locus, until now no rating system has existed indicating different levels of
      allogenicity. In order to find a theoretical approach to this problem we propose
      a rating system ('dissimilarity index') based on structural data of HLA class I
      molecules, and on published data about frequencies of naturally occurring amino
      acid exchanges. For demonstration we employ our rating system for the comparison
      of the HLA-A*23 and A*24 groups, both of which allelic products are subdivisions
      of the serological HLA-A9 family. Remarkable differences between the subtypes
      were revealed, which were superior to a simple sequence comparison. More
      surprisingly, it was uncovered that some alleles of the A*24 group showed fewer
      differences to A*2301 than to alleles within their own subtype group. Sequence
      similarity matching may serve as a starting point for the clinical evaluation of
      acceptable mismatches within the HLA-A9 family and serve as a model for other HLA
      class I groups.

PMID- 12047360
TI  - Allele frequencies of polymorphisms of TNFA, IL-6, IL-10 and IFNG in an Italian
      Caucasian population.
AB  - Polymorphisms in the regulatory and intronic regions of several cytokines have
      been associated with differential cytokine production. In this paper we
      genotyped, using the polymerase chain reaction-sequence-specific primers (PCR
      SSP) method, a series of 363 healthy Italian Caucasians with the aim of obtaining
      a reference population for further studies on the role of cytokines in the
      inflammatory and immune responses. We also compared the results to those for
      other populations. The polymorphisms analysed were those of tumour necrosis
      factor alpha (TNFA), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon
      gamma (IFNG). We found that the frequency of allele TNFA*1 at position -380 was
      87.7% and that of TNFA*2 was 12.4%, significantly different from those of the UK
      and Japanese populations but not different from that of a population in Gambia.
      For IL-10 the frequencies of alleles -1082A and -1082G were 63.0% and 37.0% and
      those of alleles -819C, - 819T, -592C and -592A were 70.8, 29.2, 70.8 and 29.2%,
      respectively, significantly different from those observed in south-east England,
      in Manchester and in an Oriental population from southern China. The frequencies
      of IL-6 alleles - 174C and -174G were 29.0 and 71.0%, respectively; for IFNG
      polymorphisms at position -874, in the population under evaluation, the alleles 
      874T and -874A were present in 44.7 and 55.3% of the subjects, respectively.
      Genotype frequencies of IL-6 were significantly different from those observed in
      populations from Germany and from the UK. The analysis carried out by our group
      indicates that there is heterogeneity in the frequencies of the cytokine
      polymorphisms among the different Caucasian populations, and this underlines the
      importance of a 'local' reference population when evaluating the clinical
      relevance of cytokine gene polymorphisms.

PMID- 12047361
TI  - TAP1 and TAP2 gene polymorphism in rheumatoid arthritis in a population in
      eastern France.
AB  - The 'transporter associated with antigen processing' (TAP) gene products are
      involved in the processing of endogenous peptides that bind to class I molecules.
      Polymorphism within these genes could alter the level of the immune response, a
      phenomenon relevant to the development of autoimmune diseases. In this study, we
      examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid
      arthritis (RA). TAP1 and TAP2 typing was performed for 138 Caucasian RA patients
      and 100 healthy controls, all originating from eastern France. TAP1 polymorphic
      residues at positions 333 and 637 and amino acid variants 379, 565, 651 and 665
      in the TAP2 gene were found using amplification refractory mutation system
      polymerase chain reaction (ARMS-PCR). This method enabled us to determine four
      TAP1 alleles (TAP1A to TAP1D) and eight TAP2 alleles (TAP2A to TAP2H). All
      patients and controls had been HLA-DRB1* genotyped. The polymorphic residues
      TAP1333 and TAP1637 did not show any difference in their distribution between
      patients and controls. Similar findings were obtained for TAP2379 and TAP2665.
      However, we found an increased frequency of Thr homozygosity and heterozygosity
      at position 565 in the TAP2 gene in RA patients (RA vs. controls: 25.3 vs. 14%; P
      = 0.032; OR = 2.09; CI = 1.01-4.38). Similarly, the prevalence of subjects who
      were homozygote and heterozygote for Cys651 was increased in the RA group (RA vs.
      controls: 36.8 vs. 11%; P = 0.02). The dimorphic site TAP2565 defines TAP2D and
      TAP2E alleles, while the site at position 651 characterizes TAP2F. Thus, we found
      that TAP2D and TAP2E alleles were more prevalent in RA, but not significantly so
      (RA vs. controls: TAP2D: 10 vs. 3.6%; P = 0.24; TAP2E: 3.6 vs. 0%; P = 0.19).
      Similarly, the frequency of TAP2F was higher in RA patients (24.5%) than in
      controls (11.3%), but this was not significant after correction (P = 0.029; Pcorr
      = 0.17). Finally, we found no linkage disequilibrium between DRB1* RA-associated
      alleles and amino acid substitution Thr565 or TAP2D and TAP2E alleles, whereas
      Cys651 (and TAP2F) was not independent of DRB1*04, a strongly RA-associated
      allele. Finally, Thr at position 565 in the TAP2 gene was associated with
      manifestations of disease severity in only a few patients. Examination of TAP1
      and TAP2 gene polymorphisms in RA patients revealed an association between a
      particular amino acid residue, namely Thr565 in the TAP2 gene, and RA. This
      association was found to be weak and did not seem to be a predictor for the
      severity of the disease.

PMID- 12047362
TI  - CTLA-4 49 A/G dimorphism and type 1 diabetes susceptibility: a French case
      control study and segregation analysis. Evidence of a maternal effect.
AB  - Several studies have demonstrated an association of cytotoxic T lymphocyte
      associated molecule 4 (CTLA-4) (IDDM 12) alanine 17 with type 1 diabetes, but we
      wished to study the parental effect of CTLA-4 49 A/G dimorphism in diabetic
      families. The CTLA-4 exon 1 polymorphism (49 A/G), HLA-DRB1 and insulin gene
      (INS) variable number tandem repeats (VNTR) were analysed in 134 type 1 diabetic
      patients vs. 273 control subjects. The segregation analysis for transmission was
      carried out in 70 informative diabetic families using the transmission distortion
      test (TDT). All genotyping was performed by PCR-RFLP. CTLA-4 49 G allele
      frequency was not increased in diabetic patients compared to controls (41 vs.
      38%, not significant). The distribution of GG, AG and AA CTLA-4 genotypes was
      similar in the two groups (13, 57 and 30% vs. 11, 54 and 35%, respectively) and
      was independent of HLA-DRB1 or INS VNTR polymorphism. The CTLA-4 49 G allele
      showed weak distorted transmission to the diabetic offspring, whereas random
      transmission was observed in unaffected offspring. This distortion is
      attributable to a maternal effect (71% compared to the 50% expected ratio; tdt =
      4.8; P < 0.03). The combined transmission of maternal CTLA-4 G with HLA-DRB1*03
      (90%; tdt = 6.4; P < 0.01) and VNTR class I (80%; tdt = 5.4; P < 0.02) enhanced
      the susceptibility effect of each marker separately. We noted a slight CTLA-4 49
      G and HLA-DRB1*04 distortion of transmission shared in paternal and maternal
      diabetic meiosis. In non-diabetic offspring, the CTLA-4 49 A allele confers a
      protective effect in the presence of maternal HLA-DRB1*03 and paternal HLA
      DRB1*04 alleles. Despite the absence of a positive association of the CTLA-4 49 G
      allele with type 1 diabetes, our segregation analysis supports the hypothesis of
      a modulation by CTLA-4 49 G/A dimorphism of the susceptibility conferred by
      maternal HLA-DRB1*03 inheritance. This potential parental effect needs to be
      confirmed in a larger data set.

PMID- 12047363
TI  - HLA-DPB1 allelic frequency of the Pumi ethnic group in south-west China and
      evolutionary relationship of Pumi with other populations.
AB  - A sequencing-based typing of the HLA-DPB1 gene was carried out in 51 unrelated
      healthy individuals from the Yunnan Pumi ethnic minority. A total of 18 DPB1
      alleles, in which DPB1*0501 (52.0%) and DPB1*0402 (15.7%) greatly predominated,
      were found, of which alleles DPB1*20011, 2201, 3601, 3701, 3801, 4901, 5001 and
      8001 were recorded for the first time in the Chinese population. This may be
      because the typing methods used in previous genotyping of Chinese populations
      were of lower sensitivity than that used in our study. A dendrogram constructed
      by the maximum likelihood method showed that the Pumi ethnic minority belongs to
      the Asian/Australasian cluster and has the closest relationship to Trobriander,
      implying an unusual relationship between Australasian and South China
      populations. However, the Yi ethnic minority, which also comes from the ancient
      Qiang, did not show a very close relationship with the Pumi. This is probably
      because the Pumi were historically assimilated by local south-west China
      populations.

PMID- 12047364
TI  - Asthma and IL-4 receptor alpha gene variants.
AB  - Linkage of allergy to chromosome 16 has been described in several studies,
      together with a positive association with interleukin 4 receptor alpha gene
      variants. Our aim was to replicate these findings in a sample of German and
      Swedish families recruited through sib-pairs affected by bronchial asthma. None
      of the markers showed linkage with the main phenotype of asthma or with total
      serum IgE. Seropositivity to D. pteronyssinus showed borderline significance in a
      region flanking the IL4Ralpha location. Single nucleotide polymorphisms (SNPs)
      leading to the protein exchanges I50V, E375A, C406R, S478P and Q551R in the IL-4
      receptor alpha were examined for allele sharing in sibs with asthma. Multiple
      regression analysis was performed for association with total serum IgE and
      specific IgE. Allele sharing of IL4Ralpha SNPs in asthmatic children was not
      significantly increased for any of the examined SNPs except for the
      intracytoplasmatic polymorphism 551R (0.79 vs. 0.84 expected, P = 0.044). The
      variants 50V, 478P and 551R were associated with slightly increased, and 375A and
      406R with decreased total IgE levels, all at a non-significant level. None of the
      examined IL4Ralpha variants were correlated to asthma severity. In summary, a
      single gene effect of IL4Ralpha variants or any other gene on chromosome 16 could
      not be shown in this selected population of children with asthma. As there could
      be interactions with multiple genetic and environmental factors, IL4Ralpha could
      still be involved in asthma pathogenesis.

PMID- 12047365
TI  - No linkage of the interleukin-4 receptor locus on chromosome 16p11.2-12.1 with
      sarcoidosis in German multiplex families.
AB  - We typed 241 members of 62 sarcoidosis families with 136 affected siblings for
      three single nucleotide polymorphisms of the interleukin-4 receptor alpha-chain
      gene (IL4R). Allele frequencies in patients were compared to those of healthy
      unrelated control individuals. The segregation of the three-point IL4R haplotypes
      completed by two flanking highly polymorphic microsatellite polymorphisms
      revealed no evidence for linkage of the IL4R gene locus with sarcoidosis.

PMID- 12047366
TI  - Guidelines for nomenclature usage in HLA reports: ambiguities and conversion to
      serotypes.

PMID- 12047367
TI  - Nomenclature for factors of the HLA system, update January 2002.

PMID- 12047368
TI  - Nomenclature for factors of the HLA system, update February 2002.

PMID- 12047369
TI  - Nomenclature for factors of the HLA system, update March 2002.

PMID- 12047371
TI  - Purification and characterization of novel kininogens from spotted wolffish and
      Atlantic cod.
AB  - Kininogens are multifunctional proteins found so far mainly in mammals. They
      carry vasoactive kinins as well as participate in defense, blood coagulation and
      the acute phase response. In this study, novel kininogens were isolated from
      Atlantic cod (Gadus morhua L.) and spotted wolffish(Anarhichas minor) by papain
      affinity chromatography. The molecular mass of cod kininogen determined by MALDI
      TOF mass spectrometry to be 51.0 kDa and it had pI values of 3.6, 3.9 and 4.4.
      The molecular mass of wolffish kininogen was 45.8 kDa and it had pI values of
      4.1, 4.3, 4.35 and 4.4. Partial amino-acid sequences determined from both
      kininogens showed clear homology with previously determined kininogen sequences.
      Both kininogens were found to inhibit cysteine proteinases like papain and ficin
      but they had no effect on trypsin, a serine proteinase. Wolffish kininogen
      carried alpha2,3-sialylated biantennary and triantennary N-glycans with extensive
      sialic acid O-acetylation. Cod kininogen carried similar glycan structures but
      about 1/3 of its glycans carried sulfate at their N-acetylglucosamine units.

PMID- 12047372
TI  - Human immunoglobulin A (IgA)-specific ligands from combinatorial engineering of
      protein A.
AB  - Affinity reagents capable of selective recognition of the different human
      immunoglobulin isotypes are important detection and purification tools in
      biotechnology. Here we describe the development and characterization of affinity
      proteins (affibodies) showing selective binding to human IgA. From protein
      libraries constructed by combinatorial mutagenesis of a 58-amino-acid, three
      helix bundle domain derived from the IgG-binding staphylococcal protein A,
      variants showing IgA binding were selected by using phage display technology and
      IgA monoclonal antibodies (myeloma) as target molecules. Characterization of
      selected clones by biosensor technology showed that five out of eight
      investigated affibody variants were capable of IgA binding, with dissociation
      constants (K(d)) in the range between 0.5 and 3 microm. One variant (Z(IgA1))
      showing the strongest binding affinity was further analyzed, and showed that
      human IgA subclasses (IgA(1) and IgA(2)) as well as secretory IgA were recognized
      with similar efficiencies. No detectable cross-reactivity towards human IgG, IgM,
      IgD or IgE was observed. The potential use of the Z(IgA1) affibody as a ligand in
      affinity chromatography applications was first demonstrated by selective recovery
      of IgA protein from a spiked Escherichia coli total cell lysate, using an
      affinity column containing a divalent head-to-tail Z(IgA1) affibody dimer
      construct as a ligand. In addition, efficient affinity recovery of IgA from
      unconditioned human plasma was also demonstrated.

PMID- 12047373
TI  - Role of critical charged residues in reduction potential modulation of ferredoxin
      NADP+ reductase.
AB  - Reduction potential determinations of K75E, E139K and E301A ferredoxin-NADP+
      reductases provide valuable information concerning the factors that contribute to
      tune the flavin reduction potential. Thus, while E139 is not involved in such
      modulation, the K75 side-chain tunes the flavin potential by creating a defined
      environment that modulates the FAD conformation. Finally, the E301 side-chain
      influences not only the flavin reduction potential, but also the electron
      transfer mechanism, as suggested from the values determined for the E301A mutant,
      where E(ox/rd) and E(sq/rd) shifted +41 and +102 mV, respectively, with regard to
      wild-type. Reduction potentials allowed estimation of binding energies
      differences of the FAD cofactor upon reduction.

PMID- 12047374
TI  - Two independent, light-sensing two-component systems in a filamentous
      cyanobacterium.
AB  - Two ORFs, cphA and cphB, encoding proteins CphA and CphB with strong similarities
      to plant phytochromes and to the cyanobacterial phytochrome Cph1 of Synechocystis
      sp. PCC 6803 have been identified in the filamentous cyanobacterium Calothrix sp.
      PCC7601. While CphA carries a cysteine within a highly conserved amino-acid
      sequence motif, to which the chromophore phytochromobilin is covalently bound in
      plant phytochromes, in CphB this position is changed into a leucine. Both ORFs
      are followed by rcpA and rcpB genes encoding response regulator proteins similar
      to those known from the bacterial two-component signal transduction. In
      Calothrix, all four genes are expressed under white light irradiation conditions,
      albeit in low amounts. For heterologous expression and convenient purification,
      the cloned genes were furnished with His-tag encoding sequences at their 3' end
      and expressed in Escherichia coli. The two recombinant apoproteins CphA and CphB
      bound the chromophore phycocyanobilin (PCB) in a covalent and a noncovalent
      manner, respectively, and underwent photochromic absorption changes reminiscent
      of the P(r) and P(fr) forms (red and far-red absorbing forms, respectively) of
      the plant phytochromes and Cph1. A red shift in the absorption maxima of the
      CphB/PCB complex (lambda(max) = 685 and 735 nm for P(r) and P(fr), respectively)
      is indicative for a noncovalent incorporation of the chromophore (lambda(max) of
      P(r), P(fr) of CphA: 663, 700 nm). A CphB mutant generated at the chromophore
      binding position (Leu246-->Cys) bound the chromophore covalently and showed
      absorption spectra very similar to its paralog CphA, indicating the noncovalent
      binding to be the only cause for the unexpected absorption properties of CphB.
      The kinetics of the light-induced P(fr) formation of the CphA-PCB chromoprotein,
      though similar to that of its ortholog from Synechocystis, showed differences in
      the kinetics of the P(fr) formation. The kinetics were not influenced by ATP
      (probing for autophosphorylation) or by the response regulator. In contrast, the
      light-induced kinetics of the CphB-PCB complex was markedly different, clearly
      due to the noncovalently bound chromophore.

PMID- 12047375
TI  - Effects of ATP depletion and phosphate analogues on P-glycoprotein conformation
      in live cells.
AB  - P-glycoprotein (Pgp), a membrane pump often responsible for the multidrug
      resistance of cancer cells, undergoes conformational changes in the presence of
      substrates/modulators, or upon ATP depletion, reflected by its enhanced
      reactivity with the UIC2 monoclonal antibody. When the UIC2-shift was elicited by
      certain modulators (e.g. cyclosporin A or vinblastine, but not with verapamil or
      Tween 80), the subsequent binding of other monoclonal anti-Pgp Ig sharing
      epitopes with UIC2 (e.g. MM12.10) was abolished [Nagy, H., Goda, K., Arceci, R.,
      Cianfriglia, M., Mechetner, E. & Szabo Jr, G. (2001) Eur. J. Biochem. 268, 2416
      2420]. To further study the relationship between UIC2-shift and the suppression
      of MM12.10 binding, we compared, on live cells, how ATP depletion and treatment
      of cells with phosphate analogues (sodium orthovanadate, beryllium fluoride and
      fluoro-aluminate) that trap nucleotides at the catalytic site, affect the two
      phenomena. Similarly to modulators or ATP depleting agents, all the phosphate
      analogues increased daunorubicin accumulation in Pgp-expressing cells.
      Prelabeling of ATP depleted cells with UIC2 completely abolished the subsequent
      binding of MM12.10, in accordance with the enhanced binding of the first mAb.
      Vanadate and beryllium fluoride, but not fluoro-aluminate, reversed the effect of
      cyclosporin A, preventing UIC2 binding and allowing for labeling of cells with
      MM12.10. Thus, changes in UIC2 reactivity are accompanied by complementary
      changes in MM12.10 binding also in response to direct modulation of the ATP
      binding site, confirming that conformational changes intrinsic to the catalytic
      cycle are reflected by both UIC2-related phenomena. These data also fit a model
      where the UIC2 epitope is available for antibody binding throughout the catalytic
      cycle including the step of ATP binding, to become unavailable only in the
      catalytic transition state.

PMID- 12047376
TI  - Expression and distribution of penaeidin antimicrobial peptides are regulated by
      haemocyte reactions in microbial challenged shrimp.
AB  - Penaeidins are a family of antimicrobial peptides constitutively produced and
      stored in the haemocytes of penaeid shrimp. In response to microbial stimulation,
      they are released into the blood circulation and they further attach to shrimp
      cuticle surfaces through a chitin-binding property. In the present paper, we have
      analysed their expression, regulation and distribution in shrimp tissues in
      response to experimental microbial challenge. We have shown that penaeidin mRNA
      and protein are restricted to granular haemocytes and that their expression and
      distribution are regulated through dramatic changes in haemocyte populations,
      both circulating and infiltrating shrimp tissues. Two distinct phases in the
      immune reactions were evidenced: (a) a migration of haemocytes towards the
      infection site within the first 12 h following microbial injection, with a local
      and massive release of peptides; (b) the appearance into the blood circulation
      and tissues of a haemocyte population displaying increased penaeidin
      transcriptional activity, which may correspond to a systemic reaction involving
      haemocyte proliferation process. Finally, in vitro confrontation of haemocytes
      and bacteria revealed that penaeidins are released from granular haemocytes by a
      novel phenomenon of intracellular degranulation, probably followed by the lysis
      of the cells. Furthermore, penaeidins were shown covering bacterial surfaces
      suggesting that the peptides could be involved in opsonic activity. Penaeidin
      positive bacteria were observed to be phagocytosed mainly by hyaline cells, a
      population that does not express penaeidins.

PMID- 12047377
TI  - Cloning of the manganese lipoxygenase gene reveals homology with the lipoxygenase
      gene family.
AB  - Manganese lipoxygenase was isolated to homogeneity from the take-all fungus,
      Gaeumannomyces graminis. The C-terminal amino acids and several internal peptides
      were sequenced, and the information was used to obtain a cDNA probe by RT/PCR.
      Screening of a genomic library of G. graminis yielded a full-length clone of the
      Mn-Lipoxygenase gene. cDNA analysis showed that the gene spanned 2.6 kb and
      contained one intron (133 bp). Northern blot analyses indicated two transcripts
      (2.7 and 3.1 kb). The deduced amino-acid sequence of the Mn-Lipoxygenase
      precursor (618 amino acids, 67.7 kDa) could be aligned with mammalian and plant
      lipoxygenases with 23-28% identity over 350-400 amino-acid residues of the
      catalytic domains. Lipoxygenases have one water molecule and five amino acids as
      Fe ligands. These are two histidine residues in the highly conserved 30 amino
      acid sequence WLLAK-X15-H-X4-H-X3-E of alpha helix 9, one histidine and usually
      an asparaine residue in the sequence H-X3-N-X-G of alpha helix 18, and the
      carboxyl oxygen of the C-terminal isoleucine (or valine) residue. The homologous
      sequence of alpha helix 9 of Mn-Lipoxygenase [WLLAK-X14-H(294)-X3-H(297)-X3-E]
      contained two single-amino-acid gaps, but otherwise His294 and His297 aligned
      with the two His residues, which coordinate iron. Mn-Lipoxygenase [H(478)-X3
      N(482)-X-G] could be aligned with the two metal ligands of alpha helix 18, and
      the C-terminal residue was Val618. We conclude that Mn-Lipoxygenase belongs to
      the lipoxygenase gene family and that its unique biochemical properties might be
      related to structural differences in the metal centre and alpha helix 9 of
      lipoxygenases rather than to the metal ligands.

PMID- 12047378
TI  - Group IID heparin-binding secretory phospholipase A(2) is expressed in human
      colon carcinoma cells and human mast cells and up-regulated in mouse inflammatory
      tissues.
AB  - Group IID secretory phospholipase A(2) (sPLA(2)-IID), a heparin-binding sPLA(2)
      that is closely related to sPLA(2)-IIA, augments stimulus-induced cellular
      arachidonate release in a manner similar to sPLA(2)-IIA. Here we identified the
      residues of sPLA(2)-IID that are responsible for heparanoid binding, are and
      therefore essential for cellular function. Mutating four cationic residues in the
      C-terminal portion of sPLA(2)-IID resulted in abolition of its ability to
      associate with cell surface heparan sulfate and to enhance stimulus-induced
      delayed arachidonate release, cyclooxygenase-2 induction, and prostaglandin
      generation in 293 cell transfectants. As compared with several other group II
      subfamily sPLA(2)s, which were equally active on A23187- and IL-1-primed cellular
      membranes, sPLA(2)-IID showed apparent preference for A23187-primed membranes.
      Several human colon carcinoma cell lines expressed sPLA(2)-IID and sPLA(2)-X
      constitutively, the former of which was negatively regulated by IL-1. sPLA(2)
      IID, but not other sPLA(2) isozymes, was expressed in human cord blood-derived
      mast cells. The expression of sPLA(2)-IID was significantly altered in several
      tissues of mice with experimental inflammation. These results indicate that
      sPLA(2)-IID may be involved in inflammation in cell- and tissue-specific manners
      under particular conditions.

PMID- 12047379
TI  - Cloning and characterization of novel snake venom proteins that block smooth
      muscle contraction.
AB  - In this study, we isolated a 25-kDa novel snake venom protein, designated
      ablomin, from the venom of the Japanese Mamushi snake (Agkistrodon blomhoffi).
      The amino-acid sequence of this protein was determined by peptide sequencing and
      cDNA cloning. The deduced sequence showed high similarity to helothermine from
      the Mexican beaded lizard (Heloderma horridum horridum), which blocks voltage
      gated calcium and potassium channels, and ryanodine receptors. Ablomin blocked
      contraction of rat tail arterial smooth muscle elicited by high K+-induced
      depolarization in the 0.1-1 microm range, but did not block caffeine-stimulated
      contraction. Furthermore, we isolated three other proteins from snake venoms that
      are homologous to ablomin and cloned the corresponding cDNAs. Two of these
      homologous proteins, triflin and latisemin, also inhibited high K+-induced
      contraction of the artery. These results indicate that several snake venoms
      contain novel proteins with neurotoxin-like activity.

PMID- 12047380
TI  - A functional role of the membrane-proximal extracellular domains of the signal
      transducer gp130 in heterodimerization with the leukemia inhibitory factor
      receptor.
AB  - gp130 is the common signal transducing receptor subunit of interleukin (IL)-6
      type cytokines. gp130 either homodimerizes in response to IL-6 and IL-11 or forms
      heterodimers with the leukemia inhibitory factor (LIF) receptor (LIFR) in
      response to LIF, oncostatin M (OSM), ciliary neurotrophic factor (CNTF),
      cardiotrophin-1 (CT-1) or cardiotrophin-like cytokine resulting in the onset of
      cytoplasmic tyrosine phosphorylation cascades. The extracellular parts of both
      gp130 and LIFR consist of several Ig-like and fibronectin type III-like domains.
      The role of the membrane-distal domains of gp130 (D1, D2, D3) and LIFR in ligand
      binding is well established. In this study we investigated the functional
      significance of the membrane-proximal domains of gp130 (D4, D5, D6) in respect to
      heterodimerization with LIFR. Deletion of each of the membrane-proximal domains
      of gp130 (Delta 4, Delta 5 and Delta 6) leads to LIF unresponsiveness.
      Replacement of the gp130 domains by the corresponding domains of the related GCSF
      receptor either restores weak LIF responsiveness (D4-GCSFR), leads to
      constitutive activation of gp130 (D5-GCSFR) or results in an inactive receptor
      (D6-GCSFR). Mutation of a specific cysteine in D5 of gp130 (C458A) leads to
      constitutive heterodimerization with the LIFR and increased sensitivity towards
      LIF stimulation. Based on these findings, a functional model of the gp130-LIFR
      heterodimer is proposed that includes contacts between D5 of gp130 and the
      corresponding domain D7 of the LIFR and highlights the requirement for both
      receptor dimerization and adequate receptor orientation as a prerequisite for
      signal transduction.

PMID- 12047381
TI  - Importin alpha binds to an unusual bipartite nuclear localization signal in the
      heterogeneous ribonucleoprotein type I.
AB  - The heterogeneous nuclear ribonucleoprotein (hnRNP) type I, a modulator of
      alternative splicing, localizes in the nucleoplasm of mammalian cells and in a
      discrete perinucleolar structure. HnRNP I contains a novel type of bipartite
      nuclear localization signal (NLS) at the N-terminus of the protein that we have
      previously named nuclear determinant localization type I (NLD-I). Recently, a
      neural counterpart of hnRNP I has been identified that contains a putative NLS
      with two strings of basic amino acids separated by a spacer of 30 residues. In
      the present study we show that the neural hnRNP I NLS is necessary and sufficient
      for nuclear localization and represents a variant of the novel bipartite NLS
      present in the NLD-I domain. Furthermore, we demonstrate that the NLD-I is
      transported into the nucleus by cytoplasmic factor(s) with active transport
      modality. Binding assays using recombinant importin alpha show an interaction
      with NLD-I similar to that of SV40 large T antigen NLS. Deletion analysis
      indicates that both stretches of basic residues are necessary for binding to
      importin alpha. The above experimental results lead to the conclusion that
      importin alpha acts as cytoplasmic receptor for proteins characterized by a
      bipartite NLS signal that extends up to 37 residues.

PMID- 12047382
TI  - The role of arginine residues in substrate binding and catalysis by
      deacetoxycephalosporin C synthase.
AB  - Deacetoxycephalosporin C synthase (DAOCS) catalyses the oxidative ring expansion
      of penicillin N, the committed step in the biosynthesis of cephamycin C by
      Streptomyces clavuligerus. Site-directed mutagenesis was used to investigate the
      seven Arg residues for activity (74, 75, 160, 162, 266, 306 and 307), selected on
      the basis of the DAOCS crystal structure. Greater than 95% of activity was lost
      upon mutation of Arg-160 and Arg266 to glutamine or other residues. These results
      are consistent with the proposed roles for these residues in binding the
      carboxylate linked to the nucleus of penicillin N (Arg160 and Arg162) and the
      carboxylate of the alpha-aminoadipoyl side-chain (Arg266). The results for
      mutation of Arg74 and Arg75 indicate that these residues play a less important
      role in catalysis/binding. Together with previous work, the mutation results for
      Arg306 and Arg307 indicate that modification of the C-terminus may be profitable
      with respect to altering the penicillin side-chain selectivity of DAOCS.

PMID- 12047383
TI  - Purification and characterization of VanXY(C), a D,D-dipeptidase/D,D
      carboxypeptidase in vancomycin-resistant Enterococcus gallinarum BM4174.
AB  - VanXY(C), a bifunctional enzyme from VanC-phenotype Enterococcus gallinarum
      BM4174 that catalyses D,D-peptidase and D,D-carboxypeptidase activities, was
      purified as the native protein, as a maltose-binding protein fusion and with an N
      terminal tag containing six histidine residues. The kinetic parameters of His(6)
      VanXY(C) were measured for a variety of precursors of peptidoglycan synthesis
      involved in resistance: for D-Ala-D-Ala, the K(m) was 3.6 mm and k(cat), 2.5 s(
      1); for UDP-MurNAc-L-Ala-D-Glu-L-Lys-DAla-D-Ala (UDP-MurNAc-pentapeptide[Ala]),
      K(m) was 18.8 mm and k(cat) 6.2 s(-1); for D-Ala-D-Ser, K(m) was 15.5 mm and
      k(cat) 0.35 s(-1). His(6)-VanXYC was inactive against the peptidoglycan precursor
      UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ser (UDP-MurNAc-pentapeptide[Ser]). The rate
      of hydrolysis of the terminal D-Ala of UDP-MurNAc-pentapeptide[Ala] was inhibited
      30% by 2 mm D-Ala-D-Ser or UDP-MurNAc-pentapeptide[Ser]. Therefore preferential
      hydrolysis of substrates terminating in D-Ala would occur during peptidoglycan
      synthesis in E. gallinarum BM4174, leaving precursors ending in D-Ser with a
      lower affinity for glycopeptides to be incorporated into peptidoglycan. Mutation
      of an aspartate residue (Asp59) of His-tagged VanXY(C) corresponding to Asp68 in
      VanX to Ser or Ala, resulted in a 50% increase and 73% decrease, respectively, of
      the specificity constant (k(cat)/K(m)) for D-Ala-D-Ala. This situation is in
      contrast to VanX in which mutation of Asp68-->Ala produced a greater than 200,000
      fold decrease in the substrate specificity constant. This suggests that Asp59,
      unlike Asp68 in VanX, does not have a pivotal role in catalysis.

PMID- 12047384
TI  - Substrate specificity of human kallikrein 2 (hK2) as determined by phage display
      technology.
AB  - Human glandular kallikrein 2 (hK2) is a trypsin-like serine protease expressed
      predominantly in the prostate epithelium. Recently, hK2 has proven to be a useful
      marker that can be used in combination with prostate specific antigen for
      screening and diagnosis of prostate cancer. The cleavage by hK2 of certain
      substrates in the proteolytic cascade suggest that the kallikrein may be involved
      in prostate cancer development; however, there has been very little other
      progress toward its biochemical characterization or elucidation of its true
      physiological role. In the present work, we adapt phage substrate technology to
      study the substrate specificity of hK2. A phage-displayed random pentapeptide
      library with exhaustive diversity was generated and then screened with purified
      hK2. Phages displaying peptides susceptible to hK2 cleavage were amplified in
      eight rounds of selection and genes encoding substrates were transferred from the
      phage to a fluorescent system using cyan fluorescent protein (derived from green
      fluorescent protein) that enables rapid determination of specificity constants.
      This study shows that hK2 has a strict preference for Arg in the P1 position,
      which is further enhanced by a Ser in P'1 position. The scissile bonds identified
      by phage display substrate selection correspond to those of the natural
      biological substrates of hK2, which include protein C inhibitor, semenogelins,
      and fibronectin. Moreover, three new putative hK2 protein substrates, shown
      elsewhere to be involved in the biology of the cancer, have been identified thus
      reinforcing the importance of hK2 in prostate cancer development.

PMID- 12047385
TI  - Isolation and characterization of MUC15, a novel cell membrane-associated mucin.
AB  - The present work reports isolation and characterization of a highly glycosylated
      protein from bovine milk fat globule membranes, known as PAS III. Partial amino
      acid sequencing of the purified protein allowed construction of degenerate
      oligonucleotide primers, enabling isolation of a full-length cDNA encoding a
      protein of 330 amino-acid residues. N-terminal amino-acid sequencing of derived
      peptides and the purified protein confirmed 76% of the sequence and demonstrated
      presence of a cleavable signal peptide of 23 residues, leaving a mature protein
      of 307 amino acids. Database searches showed no homology to any other proteins. A
      survey of the human genome indicated the presence of a corresponding gene on
      chromosome band 11p14.3. Isolation and sequencing of the complete cDNA sequence
      of the human homologue proved the existence of the gene product (334 amino-acid
      residues). This novel mucin-like protein was named MUC15 by appointment of the
      HUGO Gene Nomenclature Committee. The deduced amino-acid sequences of human and
      bovine MUC15 demonstrated structural hallmarks characteristic for other membrane
      bound mucins, such as a serine, threonine, and proline-rich extracellular region
      with several potential glycosylation sites, a putative transmembrane domain, and
      a short cytoplasmic C-terminal. We have shown the presence of O-glycosylations,
      identified N-glycosylations at 11 of 15 potential sites in bovine MUC15, and a
      splice variant encoding a short secreted mucin. Finally, analysis of human and
      bovine cDNA panels and libraries showed MUC15 gene expression in adult human
      spleen, thymus, prostate, testis, ovary, small intestine, colon, peripheral blood
      leukocyte, bone marrow, lymph node, tonsil, breast, fetal liver, bovine lymph
      nodes and lungs of both species.

PMID- 12047386
TI  - In vitro gene therapy of mucopolysaccharidosis type I by lentiviral vectors.
AB  - Mucopolysaccharidosis type I (MPS I) results from a deficiency in the enzyme
      alpha-L-iduronidase (IDUA), and is characterized by skeletal abnormalities,
      hepatosplenomegaly and neurological dysfunction. In this study, we used a late
      generation lentiviral vector to evaluate the utility of this vector system for
      the transfer and expression of the human IDUA cDNA in MPS I fibroblasts. We
      observed that the level of enzyme expression in transduced cells was 1.5-fold the
      level found in normal cells; the expression persisted for at least two months. In
      addition, transduced MPS I fibroblasts were capable of clearing intracellular
      radiolabeled glycosaminoglycan (GAG). Pulse-chase experiments on transduced
      fibroblasts showed that the recombinant enzyme was synthesized as a 76-kDa
      precursor form and processed to a 66-kDa mature form; it was released from
      transduced cells and was endocytosed into a second population of untreated MPS I
      fibroblasts via a mannose 6-phosphate receptor. These results suggest that the
      lentiviral vector may be used for the delivery and expression of the IDUA gene to
      cells in vivo for treatment of MPS I.

PMID- 12047387
TI  - The porcine trophoblastic interferon-gamma, secreted by a polarized epithelium,
      has specific structural and biochemical properties.
AB  - At the time of implantation in the maternal uterus, the trophectoderm of the pig
      blastocyst is the source of a massive secretion of interferon-gamma (IFN-gamma),
      together with lesser amounts of IFN-delta, a unique species of type I IFN. This
      trophoblastic IFN-gamma (TrIFN-gamma) is an unprecedented example of IFN-gamma
      being produced spontaneously by an epithelium. We therefore studied some of its
      structural and biochemical properties, by comparison with pig IFN-gamma from
      other sources, either natural LeIFN-gamma (from adult leucocytes), or
      recombinant. Biologically active TrIFN-gamma is a dimeric molecule, of which
      monomers are mainly composed of a truncated polypeptide chain with two
      glycotypes, unlike LeIFN-gamma which is formed of at least two polypeptide chains
      and four glycotypes. TrIFN-gamma collected in the uterus lumen was enzymatically
      deglycosylated and analysed by mass spectrometry (MALDI-TOF). The data revealed
      that the more abundant polypeptide has a mass of 14.74 kDa, corresponding to a C
      terminal cleavage of 17 residues from the expected 143-residue long mature
      sequence. A minor polypeptide, with a mass of 12.63 kDa, corresponds to a C
      terminal truncation of 36 amino acids. MALDI-TOF analysis of tryptic peptides
      from the glycosylated molecule(s) identifies a single branched carbohydrate
      motif, with six N-acetylgalactosamines, and no sialic acid. The only glycan
      microheterogeneity seems to reside in the number of l-fucose residues (one to
      three). The lack of the C-terminal cluster of basic residues, and the presence of
      nonsialylated glycans, result in a very low net charge of TrIFN-gamma molecule.
      However, the 17-residue truncation does not affect the antiproliferative activity
      of TrIFN-gamma on different cells, among which is a porcine uterine epithelial
      cell line. It is suggested that these specific properties might confer on TrIFN
      gamma a particular ability to invade the uterine mucosa and exert biological
      functions beyond the endometrial epithelium.

PMID- 12047388
TI  - Azidothymidine causes functional and structural destruction of mitochondria,
      glutathione deficiency and HIV-1 promoter sensitization.
AB  - Mitochondrial functional and structural impairment and generation of oxidative
      stress have been implicated in aging, various diseases and chemotherapies. This
      study analyzed azidothymidine (AZT)-caused failures in mitochondrial functions,
      in redox regulation and activation of the HIV-1 gene expression. We monitored
      intracellular concentrations of ATP and glutathione (GSH) as the indicators of
      energy production and redox conditions, respectively, during the time-course
      experiments with U937 and MOLT4 human lymphoid cells in the presence of AZT (0.05
      mg x mL(-1)) or H(2)O(2) (0.01 mm) for 15-25 days. Mitochondrial DNA integrity
      and NF-kappa B-driven HIV-1 promoter activity were also assessed. ATP
      concentration began to decrease within several days after exposure to AZT or
      H(2)O(2), and the decrease continued to reach 30-40% of the normal level.
      However, decline of GSH was detectable after a retention period for at least 5-6
      days, and progressed likewise. PCR analyses found that mitochondrial DNA
      destruction occurred when the ATP and GSH depletion had progressed, detecting a
      difference in the deletion pattern between AZT and H(2)O(2)-treated cells. The
      GSH decrease coincided with HIV-1 promoter sensitization detected by enhanced DNA
      binding ability of NF-kappa B and induction of the gene expression upon H(2)O(2)
      rechallenge. Our results suggest that, in the process of AIDS myopathy
      development, AZT or oxidative agents directly impair the energy-producing system
      of mitochondria, causing dysfunction of cellular redox control, which eventually
      leads to loss of the mitochondrial DNA integrity. The mechanism of cellular redox
      condition-mediated NF-kappa B activation is discussed.

PMID- 12047389
TI  - Suppression of apolipoprotein C-II amyloid formation by the extracellular
      chaperone, clusterin.
AB  - The effect of the extracellular chaperone, clusterin, on amyloid fibril formation
      by lipid-free human apolipoprotein C-II (apoC-II) was investigated. Sub
      stoichiometric levels of clusterin, derived from either plasma or semen, potently
      inhibit amyloid formation by apoC-II. Inhibition is dependent on apoC-II
      concentration, with more effective inhibition by clusterin observed at lower
      concentrations of apoC-II. The average sedimentation coefficient of apoC-II
      fibrils formed from apoC-II (0.3 mg.mL-1) is reduced by coincubation with
      clusterin (10 microg x mL(-1)). In contrast, addition of clusterin (0.1 mg x mL(
      1)) to preformed apoC-II amyloid fibrils (0.3 mg x mL(-1)) does not affect the
      size distribution after 2 days. This sedimentation velocity data suggests that
      clusterin inhibits fibril growth but does not promote fibril dissociation.
      Electron micrographs indicate similar morphologies for amyloid fibrils formed in
      the presence or absence of clusterin. The substoichiometric nature of the
      inhibition suggests that clusterin interacts with transient amyloid nuclei
      leading to dissociation of the monomeric subunits. We propose a general role for
      clusterin in suppressing the growth of extracellular amyloid.

PMID- 12047390
TI  - Analysis of flux estimates based on (13)C-labelling experiments.
AB  - Modelling of the fluxes in central metabolism can be performed by combining
      labelling experiments with metabolite balancing. Using this approach, multiple
      samples from a cultivation of Saccharomyces cerevisiae in metabolic and isotopic
      steady state were analysed, and the metabolic fluxes in central metabolism were
      estimated. In the various samples, the estimates of the central metabolic
      pathways, the tricarboxylic acid cycle, the oxidative pentose phosphate pathway
      and the anaplerotic pathway, showed an unprecedented reproducibility. The high
      reproducibility was obtained with fractional labellings of individual carbon
      atoms as the calculational base, illustrating that the more complex modelling
      using isotopomers is not necessarily superior with respect to reproducibility of
      the flux estimates. Based on these results some general difficulties in flux
      estimation are discussed.

PMID- 12047391
TI  - Refolding of the Escherichia coli expressed extracellular domain of alpha 7
      nicotinic acetylcholine receptor.
AB  - Heterologous expression of the extracellular domains (ECDs) of the nicotinic
      acetylcholine receptor (AChR) subunits may give large amounts of proteins for
      studying the functional and spatial characteristics of their ligand-binding
      sites. The ECD of the alpha 7 subunit of the homo-oligomeric alpha 7 neuronal
      AChR appears to be a more suitable object than the ECDs of other heteromeric
      neuronal or muscle-type AChRs. The rat alpha 7 ECDs (amino-acid residues
      approximately 1-210) were recently expressed in Escherichia coli as fusion
      proteins with maltose-binding protein [Fischer, M., Corringer, P., Schott, K.,
      Bacher, A. & Changeux, J. (2001) Proc. Natl Acad. Sci. USA 98, 3567-3570] and
      glutathione S-transferase (GST) [Utkin, Y., Kukhtina, V., Kryukova, E., Chiodini,
      F., Bertrand, D., Methfessel, C. & Tsetlin, V. (2001) J. Biol. Chem. 276, 15810
      15815]. However, these proteins exist in solution mostly as high-molecular mass
      aggregates rather than monomers or oligomers. In the present work it is found
      that refolding of GST-alpha 7-(1-208) protein in the presence of 0.1% SDS
      considerably decreases the formation of high-molecular mass aggregates. The C116S
      mutation in the alpha 7 moiety was found to further decrease the aggregation and
      to increase the stability of protein solutions. This mutation slightly increased
      the affinity of the protein for alpha-bungarotoxin (from Kd approximately 300 to
      150 nm). Gel-permeation HPLC was used to isolate the monomeric form of the GST
      alpha 7-(1-208) protein and its mutant almost devoid of SDS. CD spectra revealed
      that the C116S mutation considerably increased the content of beta structure and
      made it more stable under different conditions. The monomeric C116S mutant
      appears promising both for further structural studies and as a starting material
      for preparing the alpha 7 ECD in an oligomeric form.

PMID- 12047392
TI  - Phosphorylation of initiation factor-2 alpha is required for activation of
      internal translation initiation during cell differentiation.
AB  - The long uORF-burdened 5'UTRs of many genes encoding regulatory proteins involved
      in cell growth and differentiation contain internal ribosomal entry site (IRES)
      elements. In a previous study we showed that utilization of the weak IRES of
      platelet-derived growth factor (PDGF2) is activated during megakaryocytic
      differentiation. The establishment of permissive conditions for IRES-mediated
      translation during differentiation has been confirmed by our demonstration of the
      enhanced activity of vascular endothelial growth factor, c-Myc and
      encephalomyocarditis virus IRES elements under these conditions, although their
      mRNAs are not naturally expressed in differentiated K562 cells. In contrast with
      the enhancement of IRES-mediated protein synthesis during differentiation, global
      protein synthesis is reduced, as judged by polysomal profiles and radiolabelled
      amino acid incorporation rate. The reduction in protein synthesis rate correlates
      with increased phosphorylation of the translation initiation factor eIF2 alpha.
      Furthermore, IRES use is decreased by over-expression of the dominant-negative
      form of the eIF2 alpha kinase, PKR, the vaccinia virus K3L gene, or the eIF2
      alpha-S51A variant which result in decreased eIF2 alpha phosphorylation. These
      data demonstrate a connection between eIF2 alpha phosphorylation and activation
      of cellular IRES elements. It suggests that phosphorylation of eIF2 alpha, known
      to be important for cap-dependent translational control, serves to fine-tune the
      translation efficiency of different mRNA subsets during the course of
      differentiation and has the potential to regulate expression of IRES-containing
      mRNAs under a range of physiological circumstances.

PMID- 12047393
TI  - Role of leptin in glucose metabolism in type 2 diabetes.

PMID- 12047394
TI  - Hormonal influences on lipoprotein(a) metabolism.

PMID- 12047395
TI  - Cardiovascular effects of raloxifene: the potential for cardiovascular protection
      in women.

PMID- 12047396
TI  - Nateglinide improves glycaemic control when added to metformin monotherapy:
      results of a randomized trial with type 2 diabetes patients.
AB  - AIMS/HYPOTHESIS: This study evaluated the addition of nateglinide, a d
      phenylalanine derivative that restores early phase insulin release, to metformin
      in type 2 diabetes patients stabilized on high-dose metformin. METHODS: This
      multicentre, double-blind, parallel group trial included 467 metformin-treated
      patients with glycosylated haemoglobin (HbA1c) between 6.8% and 11%. Patients
      were randomized to add nateglinide 60 mg, 120 mg or placebo before three meals to
      metformin 1000 mg b.i.d. for 24 weeks. RESULTS: HbA1c was significantly reduced
      with nateglinide 60 mg and 120 mg plus metformin compared with metformin control
      (-0.36%, p = 0.003; -0.59%, p < 0.001 respectively). Greater benefits occurred if
      patients had elevated HbA1c at baseline (-1.38% with nateglinide 120 mg in
      patients with HbA1c > 9.5%). A modest fasting plasma glucose reduction was
      observed. Most symptoms suggestive of hypoglycaemia occurred in patients with low
      HbA1c levels (<or= 8%) at baseline, although no confirmed cases of hypoglycaemia
      occurred with nateglinide 60 mg in this patient group. Events suggestive of
      hypoglycaemia were confirmed in 1.1% of cases (plasma glucose <or= 3.3 mmol/l).
      Weight gain over 24 weeks was 0.9 kg with nateglinide 120 mg vs. metformin alone,
      and plasma lipids remained unchanged. CONCLUSIONS/INTERPRETATION: In patients
      stabilized on high-dose metformin, the addition of nateglinide improved glycaemic
      control. The combination of these agents was well tolerated and both doses of
      nateglinide proved effective. The efficacy of nateglinide 60 mg and the low rate
      of hypoglycaemia observed at this dose make it suitable for patients close to
      their therapeutic target on metformin monotherapy.

PMID- 12047397
TI  - Effects of gemfibrozil on insulin resistance to fat metabolism in subjects with
      type 2 diabetes and hypertriglyceridaemia.
AB  - AIM: To examine whether lowering of plasma triglyceride concentrations using the
      fibrate peroxisome proliferator-activated receptor (PPAR)alpha agonist
      gemfibrozil would influence insulin sensitivity to various aspects of
      intermediary metabolism among subjects with type 2 diabetes mellitus. METHODS: A
      randomized placebo-controlled double-blind study in 12 subjects with type 2
      diabetes were treated for 12 weeks after a 12-week dietary run-in. Insulin
      sensitivity was assessed using a low-dose incremental intravenous insulin
      infusion. RESULTS: Gemfibrozil significantly reduced fasting serum triglyceride
      concentrations (p < 0.001) but had no effect on measures of diabetic control.
      Neither gemfibrozil nor placebo treatment altered insulin sensitivity of glucose
      or glycerol metabolism during low-dose insulin infusion, but significant falls in
      both non-esterified fatty acid (NEFA) (p = 0.003) and ketone concentrations (p =
      0.002) were observed after treatment with gemfibrozil. CONCLUSIONS: Gemfibrozil
      does not affect insulin sensitivity to glucose or fat metabolism in type 2
      diabetes but enhances the lowering of plasma NEFA concentrations by insulin,
      probably by reducing hepatic fatty acid synthesis.

PMID- 12047398
TI  - Effect of misoprostol (PGE1) on glucose metabolism in type-2-diabetic and control
      subjects.
AB  - In vitro and in vivo studies have demonstrated that prostaglandins of the E
      series enhance muscle glucose uptake. We examined the effect of acute misoprostol
      (PGE1) administration on whole body insulin-mediated glucose disposal, as well as
      the major intracellular pathways of glucose metabolism in type 2 diabetic (n =
      10) and non-diabetic (n = 4) subjects. Each subject received two 240-min
      euglycaemic insulin (40 mU/m2/min) clamp studies with tritiated glucose and
      indirect calorimetry. During one of the insulin clamp studies, 200 microg of
      misoprostol was ingested at 90 and 150 min after the start of the insulin
      infusion. Insulin-mediated total body glucose disposal, glycolysis, glycogenesis
      and glucose oxidation were similar during the insulin clamp studies performed
      without and with misoprostol in both the diabetic and non-diabetic groups. These
      results demonstrate that the acute administration of misoprostol does not enhance
      insulin-mediated glucose disposal in either type-2-diabetic or non-diabetic
      subjects.

PMID- 12047399
TI  - Simultaneous glyburide/metformin therapy is superior to component monotherapy as
      an initial pharmacological treatment for type 2 diabetes.
AB  - OBJECTIVE: To evaluate whether simultaneous initial treatment of both insulin
      resistance and impaired beta-cell insulin secretion with glyburide/metformin
      tablets is superior to monotherapy with each component agent. RESEARCH DESIGN AND
      METHODS: In this randomized, parallel-group, placebo-controlled, multicentre
      study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed
      diet and exercise were randomly assigned to 4 weeks of therapy with placebo,
      glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or
      glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks
      based on glycaemic response. The primary outcome measure was change from baseline
      in mean HbA1c after 20 weeks. Changes in fasting plasma glucose, lipids and body
      weight were also assessed along with 2-h postprandial glucose and insulin values
      after a standardized meal. RESULTS: At week 20, patients taking
      glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in
      HbA1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both
      p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin
      (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more
      in both glyburide/metformin groups compared with placebo and metformin (p <
      0.001); patients in both combination therapy groups also had significantly lower
      postprandial glucose concentrations compared with placebo, glyburide and
      metformin. CONCLUSIONS: Initial combination treatment with glyburide/metformin
      tablets produces greater improvements in glycaemic control than either glyburide
      or metformin monotherapy. The superiority of initial therapy with
      glyburide/metformin tablets may arise from simultaneous treatment of both
      pathophysiological defects of type 2 diabetes.

PMID- 12047400
TI  - The regulation of HSL and LPL expression by DHT and flutamide in human
      subcutaneous adipose tissue.
AB  - Clinical observations suggest a role for testosterone in the accumulation of
      central adiposity and with an associated increased risk of disease. To date, no
      human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue
      mass regulation in vitro. This study investigated the role of DHT and androgen
      receptors (AR) in the regulation of lipolysis and lipogenesis by examining the
      key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL)
      respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were
      treated with either DHT (10(-7)-10(-9) m), an antiandrogen, flutamide (FLT: 10(
      7)-10(-9) m) or a combination of DHT (10(-7)-10(-9) m) with FLT (10(-8) m).
      Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT
      inhibited HSL expression maximally at 10(-9) m (0.7 +/- 0.4**; p < 0.01**)
      compared with control (control: 1.0 +/- (s.e.m.) 0.0), whereas LPL protein
      expression was stimulated at DHT10(-9) m (2.22 +/- 0.48*; p < 0.05*). Glycerol
      release assay results correlated with HSL expression data. LPL expression was
      reduced at all doses with combinations of DHT + FLT compared with DHT alone.
      Androgen receptor expression studies showed an inverse correlation with DHT,
      whereas DHT + FLT reduced AR expression. These studies indicate that DHT may
      alter HSL and LPL expression, whereas only LPL expression appears mediated by AR.
      These findings suggest a physiological role for DHT in the control of adipose
      tissue mass in women, and indicate that androgens may also play an important role
      in regulating lipid metabolism.

PMID- 12047401
TI  - Intravascular catheter-related infections: a growing problem, the search for
      better solutions.

PMID- 12047402
TI  - Pathogenesis of catheter-related infections: lessons for new designs.
AB  - In the last decade, two main strategies have been employed in the prevention of
      catheter-related infections: the creation of anti-adhesive biomaterials using
      physicochemical methods, and the incorporation of antimicrobial or antiseptic
      agents into current polymer biomaterials. There has been limited success with the
      first approach. Intravascular catheters and cuffs with an antimicrobial coating
      have been developed in recent years. Nevertheless, preventive strategies should
      avoid the use of therapeutic antibiotics. Exposure to antimicrobial agents could
      favor the development of resistance or the expression of genes responsible for
      biofilm formation. The use of these catheters should be restricted to situations
      where the rate of infection is high despite adherence to other strategies that do
      not incorporate antimicrobial agents. Better knowledge of the pathogenesis of
      catheter-related infections will facilitate the design of new devices that avoid
      the use of antimicrobial agents and decrease the risk of associated bloodstream
      infections. This could include the use of 'biospecific polymers' coated with anti
      adhesive molecules or the use of agents which might block the expression of genes
      controlling biofilm formation for the most prevalent pathogens.

PMID- 12047403
TI  - Catheter-related infections: diagnosis and intravascular treatment.
AB  - The diagnosis of catheter-related infections relies on the presence of clinical
      manifestations of infection and the evidence of colonization of the catheter tip
      by bacteria, mycobacteria, or fungi. The reference method to confirm the latter
      requires the withdrawal of the catheter for culturing, which frequently turns out
      to be inconvenient, unnecessary and costly. New methods try to avoid these
      drawbacks and to assess the presence of tip colonization without withdrawal.
      Comparative quantitative blood cultures with a marked increase (> or = 5) in
      colony counts between blood obtained from the catheter lumen and from a
      peripheral vein simultaneously is one of those methods. It has a high sensitivity
      (>80%) and specificity (94-100%) but it is cumbersome and requires both an easy
      backflow of blood in the catheter and the existence of bacteremia.
      Cytocentrifugation and acridine orange staining of blood withdrawn from an
      infected catheter lumen has a sensitivity and a specificity of over 90% for the
      diagnosis of tip colonization. 'Superficial cultures' comprise the
      semiquantitative culture of the hub, of the skin surrounding the catheter
      entrance and of the first subcutaneous portion (1 cm) of the catheter after
      swabbing. The sensitivity of this method is >90%, specificity is >80%, and
      positive and negative predictive values for catheters (considering together those
      with and without clinical data of infection) are 66 and 97%, respectively.
      Endoluminal brushing has proved to be an impractical and unreliable procedure, at
      least in our experience. New methods based on the speed of bacterial growth to
      detectable levels of micro-organisms in conventional blood cultures are a new and
      interesting way of assessing catheter-related infections. Moreover, as the use of
      antimicrobial-coated catheters becomes more prevalent, the existing definitions
      of catheter colonization and catheter-related infection may need to be modified,
      because such coatings may lead to false-negative culture results. Many catheter
      infections, diagnosed without catheter withdrawal, can be handled nowadays with
      the so-called 'antibiotic lock-in technique', which consists in 'locking' the
      infected catheter lumen with a solution containing antibiotics. A high proportion
      of infected catheters, mainly those with coagulase-negative staphylococci, can be
      maintained in place and sterilized with this technique, including catheters in
      patients with therapeutic failure after receiving conventional intravenous
      antibiotic therapy. New diagnostic and therapeutic techniques may avoid the
      unnecessary withdrawal of thousands of efficient, difficult to replace and
      expensive intravascular lines.

PMID- 12047404
TI  - Selection of empiric therapy in patients with catheter-related infections.
AB  - Catheter-related infections (CRI) are frequent and manifest in a wide range of
      clinical situations. A rational approach is necessary for the adequate management
      of these infections. Whenever a CRI is suspected, two main questions have to be
      addressed: whether to remove the catheter and whether to initiate empiric
      antimicrobial treatment. As the clinical diagnosis of CRI has a low specificity,
      the catheter should be removed only in circumstances such as severe or ongoing
      sepsis, persistent bacteremia, pulmonary or peripheral embolization,
      endocarditis, signs of tunnel infection, when the catheters or when the CRI is
      caused by fungi, Staphylococcus aureus or Pseudomonas aeruginosa are easy to
      replace among others. Exchanging the catheter through a guidewire is a frequent
      practice but is not recommended by some authors. Empiric antimicrobial treatment
      should be administered in any of the following situations: when the catheter is
      not removed, in the case of central venous or surgically implanted catheters and
      prosthetic implants, in the presence of severe sepsis, neutropenia or other
      immunodepressed status, suppurative phlebitis, embolization and acute
      endocarditis. Empriic antimicrobial treatment should include a glycopeptide
      (vancomycin or teicoplanin) as staphylococci are the most frequent cause of CRI.
      Adding an antipseudomonal agent, such as amikacin, aztreonam, ceftazidime,
      cefepime, piperacillin/tazobactam, or a carbapenem (depending on the local
      antimicrobial susceptibility data or antibiotic policy) is necessary in cases of
      neutropenia, burn patients, severe sepsis, or suspicion of contaminated infusate.
      Empiric treatment against Candida is not initially necessary in most cases.
      Empiric treatment should be replaced by specific therapy whenever possible.

PMID- 12047405
TI  - The antibiotic-lock technique for therapy of 'highly needed' infected catheters.
AB  - Catheter-related bacteremia is a major complication in patients with long-term
      surgically implanted central venous catheters, which are difficult and expensive
      to remove. Conventional treatment fails in a significant number of cases,
      resulting in removal of the device. The antibiotic-lock technique involves
      instilling a high concentration of antibiotic into the catheter lumen, and
      allowing it to remain for a period of time. Results of several open studies,
      mainly involving patients receiving home parenteral nutrition, indicate that this
      method may be regarded as an alternative to the conservative treatment of
      noncomplicated intraluminal catheter-related bacteremia, in which infection may
      be treated without catheter removal. However, many questions about this
      therapeutic method remain to be resolved, including appropriate concentration of
      antibiotics, duration of treatment, and whether or not concomitant systemic
      antibiotic therapy is necessary. Prospective studies comparing the antibiotic
      lock technique with conventional treatment are needed.

PMID- 12047406
TI  - Treatment of the afebrile patient after catheter withdrawal: drugs and duration.
AB  - Catheter-related infections constitute 10-15% of all nosocomial infections, and
      constitute a relevant and growing problem, with an impact that is far from
      irrelevant, especially in the intensive care unit. The most frequent pathogens
      implicated come from the skin flora; Gram-positive cocci are responsible for
      about two-thirds of the infections, and Candida has emerged as another important
      cause. Questions about drug, route of administration, dosage and duration of
      antibiotherapy for patients who have become apyretic and with no signs of sepsis
      after catheter removal are still under debate, and far from being definitively
      answered. Decisions regarding these questions are based on three main factors:
      namely, which is the microoorganism responsible for the infection, what was the
      time to response, and what kind of patient are we dealing with? However, the
      microorganism is clearly the main factor in making a decision. In summary, all
      catheter-related infections should be treated with appropriate antibiotics,
      regardless of the removal of the catheter, with parenteral drugs, using high
      doses and short courses, namely 1 week, and de-escalating to narrow-spectrum
      drugs on the basis of susceptibility tests as soon as possible. Staphylococcus
      aureus catheter-related infections constitute an exception, needing longer
      courses, as it is difficult to predict who will be high-risk patients.

PMID- 12047407
TI  - Overview of catheter-related infections with special emphasis on prevention based
      on educational programs.
AB  - Intra-vascular access is an unavoidable tool in sophisticated modern medical
      practice, and catheter-related infection remains a leading cause of nosocomial
      infections, particularly in intensive care units where it is associated with
      significant patient morbidity, mortality, and additional hospital costs. The
      incidence of catheter-related bloodstream infection ranges from 2 to 14 episodes
      per 1000 catheter-days. On average, microbiologically documented, device-related
      bloodstream infections complicate the use of a central venous line in three to
      five per 100 cases. But this represents only the visible part of the iceberg and
      most episodes of clinical sepsis are nowadays considered to be catheter-related.
      We briefly review the pathophysiology of these infections, highlighting the
      importance of the skin insertion site and the intravenous line hub as principal
      sources of colonization and infection. Principles of therapy are briefly
      addressed. A large proportion of these infections are preventable and this has
      been the objective of creating precise guidelines. It was recently suggested that
      the situation may evolve with the introduction of antibiotic/antiseptic-coated
      devices, whose impact on the epidemiology of antibiotic resistance remains to be
      determined. Recently, educational programs and/or a global preventive strategy
      based on the strict application of specific preventive measures and careful
      control of all factors associated with infection proved to be even more effective
      than coated devices in reducing rates of infection. Practical aspects regarding
      educational approaches will help clinicians to adapt and incorporate educational
      programs into clinical practice.

PMID- 12047408
TI  - The role of glycopeptides in the treatment of intravascular catheter-related
      infections.
AB  - There is increasing concern over multiresistant staphylococcci in catheter
      associated infections. Local infections due to coagulase-negative staphylococci
      are usually resolved by removal of the intravascular catheter. However, if the
      device should remain for a certain period of time, e.g. to complete a course of
      chemotherapy, the antibiotic lock technique with a glycopeptide should be
      considered. In case of septic embolism to the lung caused by a multiresistant
      Staphylococccus aureus or Enterococcus faecium, systemic therapy with
      glycopeptides, streptogramins or linezolid must be employed.

PMID- 12047409
TI  - Has cytomegalovirus infection any role in the development of atherosclerosis?
AB  - An interesting aspect of infection with several infectious agents is the possible
      association with some diseases apparently not associated with infections. One of
      the most exciting examples of this is the association of cardiovascular diseases
      with infection involving several different infectious agents. Cytomegalovirus
      (CMV) is one of the chief candidates that have been studied. Several
      epidemiologic reports indicate a possible association of various forms of
      vascular disease with the presence and titer of viral antibodies. Other studies
      show the presence of virus, viral antigens or nucleic acid in atherosclerotic
      lesions. Studies in animal models and cell-culture studies present attractive
      mechanisms by which the virus may play a role in the etiology of these diseases.
      However, negative results have also been reported, and more research is needed
      before the final verdict on this exciting question is presented.

PMID- 12047410
TI  - Birth outcome of 1886 pregnancies after exposure to phenoxymethylpenicillin in
      utero.
AB  - OBJECTIVE: To examine the risk of congenital abnormalities, preterm birth and low
      birth weight after exposure to phenoxymethylpenicillin in utero. METHODS: A
      population-based follow-up study in the County of North Jutland, Denmark. Birth
      outcome for 1886 women, who redeemed prescriptions for phenoxymethylpenicillin
      during pregnancy was compared with the outcome for 9263 women who did not redeem
      any prescription during pregnancy. RESULTS: The prevalence of congenital
      abnormalities in 654 users of phenoxymethylpenicillin with or without other drugs
      during the first trimester was 4.6% compared with 3.6% in the reference group,
      giving a prevalence odds ratio of 1.25 (95% CI: 0.84-1.86). The prevalence odds
      ratio was 1.35 (95% CI: 0.59-3.08) in 131 women who were exposed to
      phenoxymethylpenicillin only. Nine cardiovascular abnormalities were found,
      giving an adjusted prevalence odds ratio of 1.74 (95% CI: 0.83-3.65). The
      prevalence odds ratios of preterm birth and low birth weight were 0.83 (95% CI:
      0.66-1.04) and 1.02 (95% CI: 0.71-1.47), respectively. CONCLUSION: We found no
      significantly increased risk of congenital abnormalities, including
      cardiovascular abnormalities, preterm birth, or low birth weight in women who
      purchased phenoxymethylpenicillin during pregnancy.

PMID- 12047411
TI  - The characteristics of infections in crush syndrome.
AB  - OBJECTIVE: To analyze the results of clinical and bacteriological examinations of
      crush syndrome patients admitted to our institute after the Marmara earthquake.
      METHODS: Data were collected retrospectively from patients' files. Forty patients
      are included. Their mean age was 31.5 +/- 13.5 years and 18 were male. Their mean
      time under the rubble was 13.1 +/- 14.4 h. Fasciotomies were performed on 41
      extremities of 30 patients. One hundred and twelve (mean 2.9 +/- 1.9
      samples/patient) bacteriological samples were collected from wounds (51), blood
      (23), urine (25) and catheters (13). RESULTS: Microbial growth was detected in 67
      samples from 38 (95%) patients. Non-fermenting Gram-negative bacilli, Gram
      positive cocci, Enterobacteriaciace and yeast-like fungi were isolated in 67%,
      17%, 12% and 4% of the samples, respectively. Acinetobacter (36%) and Pseudomonas
      aeruginosa (21%), the major bacterial isolates from wound infections, were
      resistant to carbapenems and sensitive to quinolones. As the hospitalization
      period increased, other infections supervened. Gram-positive cocci and non
      fermenting Gram-negative bacilli were detected in six blood and seven catheter
      samples and methicillin-resistant Staphylococcus aureus was the major isolate.
      Nine (22%) of the patients died due to sepsis despite all supportive therapies.
      CONCLUSIONS: Infections are still major factors in crush syndrome-related deaths.

PMID- 12047412
TI  - Susceptibility of Enterobacteriaceae to beta-lactam agents and fluoroquinolones:
      a 3-year survey in France.
AB  - OBJECTIVE: To assess trends in the susceptibility to beta-lactam agents and to
      fluoroquinolones of clinically relevant Enterobacteriaceae isolated over a 3-year
      period in 14 French hospital laboratories. METHODS: During the second quarter of
      1996, 1997 and 1998, 180 consecutive non-duplicate isolates of Enterobacteriaceae
      were collected in each center. Sixteen beta-lactams and four quinolones were
      tested by the disk diffusion method. In addition, the double-disk synergy test
      was used to screen for the production of extended-spectrum beta-lactamase (ESBL).
      RESULTS: Totals of 2507, 2312 and 2506 clinical isolates were obtained in each
      period, respectively. The distribution of Enterobacteriaceae species according to
      clinical specimens and wards was similar in each study period. No significant
      variation in the susceptibility rates to beta-lactams and fluoroquinolones was
      observed, except in Klebsiella pneumoniae and Enterobacter aerogenes. The
      prevalence of ESBL-producing isolates decreased from 18% to 9% in the former,
      while it increased from 32% to 54% in the latter. At the same time, the
      susceptibility to ofloxacin and pefloxacin increased for K. pneumoniae (P <
      0.003) and cephalosporinase-producing species (P < 0.05), except Enterobacter
      spp. CONCLUSION: Over the 3-year study period beta-lactams and fluoroquinolones
      remained highly active against Enterobacteriaceae clinical isolates, with the
      exception of E. aerogenes, probably as a result of the dissemination of
      multiresistant clones in French hospitals.

PMID- 12047413
TI  - In vitro activity of levofloxacin against contemporary clinical isolates of
      Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae from North
      America and Europe.
AB  - OBJECTIVE: To assess the activities of levofloxacin and the comparator agents
      erythromycin, clarithromycin, azithromycin and doxycycline against atypical
      respiratory pathogens. METHODS: One hundred and forty-six Legionella pneumophila,
      41 Mycoplasma pneumoniae and nine Chlamydia pneumoniae isolates were procured
      from various culture collections in North America and Europe and tested for
      susceptibility to the above agents by broth microdilution. The isolates came
      primarily from clinical sources and were collected from patients between 1995 and
      1999. RESULTS: Against L. pneumophila, levofloxacin was the most active agent,
      with an MIC(90) of 0.03 mg/L, twofold more active than clarithromycin (0.06
      mg/L), 16-fold more active than erythromycin and azithromycin (0.5 mg/L) and 64
      fold more active than doxycycline. Against M. pneumoniae, azithromycin (MIC(90) <
      or = 0.0005 mg/L) was the most active agent. However, two isolates of M.
      pneumoniae, one from the USA and one from Finland, were macrolide resistant (MIC
      > or = 4 mg/L), but levofloxacin susceptible (MIC 0.25 mg/L). The geographic
      origin of L. pneumophila and M. pneumoniae did not affect the MIC range for any
      antimicrobial agent tested. Against C. pneumoniae, clarithromycin was the most
      active agent, with an MIC range of < or =0.008-0.03 mg/L. CONCLUSIONS:
      Levofloxacin had comparable activity to the other agents tested against the
      atypical respiratory pathogens, confirming its potential as an alternative for
      empirical therapy of community-acquired pneumonia.

PMID- 12047414
TI  - Evaluation of the VITAL (bioMerieux) automated blood culture system using blind
      subculture.
AB  - OBJECTIVE: This study was performed to determine the ability of the VITAL system
      to detect and allow recovery of microorganisms that are difficult to grow, such
      as Brucella spp., yeasts, or anaerobes, as well as to determine the need for
      blind subcultures after the incubation period. METHODS: A prospective evaluation
      of the system was performed, and 8247 blood culture bottles were processed. The
      standard was blind subculture from all the bottles after 5 days of incubation.
      RESULTS: There were 3.2% false-positive and 0.6% false-negative results (72% of
      clinical importance). The system sensitivity for yeasts was 41%. The mean time
      for detection of Neisseria meningitidis was 31.9 +/- 2.8 h, for Brucella spp.
      119.7 +/- 2 h, and for yeast 51.5 +/- 27.8 h. CONCLUSIONS: The VITAL system poses
      has serious difficulties in the detection of N. meningitidis, Brucella spp.,
      yeast and methicillin- and aminoglycoside-resistant Staphylococcus aureus
      (MARSA). The low system sensitivity for yeast detection makes the blind
      subculture necessary after the incubation period.

PMID- 12047415
TI  - Ecological impact of the des-F(6)-quinolone, BMS-284756, on the normal intestinal
      microflora.
AB  - OBJECTIVE: BMS-284756 (T-3811ME) is a novel des-F(6)-quinolone effective against
      a broad spectrum of aerobic and anaerobic pathogens. The aim of this study was to
      investigate the ecological effect of BMS-284756 on the intestinal microflora.
      METHODS: Forty healthy subjects participated in the trial. Eight subjects were
      assigned to each of five dose panels (100, 200, 400, 800 and 1200 mg BMS-284756)
      and received daily oral dosing with either BMS-284756 (n = 6) or placebo (n = 2)
      for 14 days. Fecal samples were collected before (days -2 and -1), during (days 7
      and 14), and after (days 21, 28, and 45) completion of the administration period.
      RESULTS: In subjects receiving 100 or 200 mg BMS-284756, no significant changes
      in the intestinal aerobic and anaerobic microflora occurred. The number of
      enterococci, bacilli, corynebacteria, bifidobacteria, lactobacilli, clostridia
      and bacteroides decreased in subjects receiving 400 or 800 mg BMS-284756, whereas
      the number of eubacteria increased. Subjects who received 1200 mg BMS-284756 had
      significant changes in the microflora: enterococci, bacilli, corynebacteria,
      enterobacteria, bifidobacteria, lactobacilli, clostridia and bacteroides were
      suppressed, whereas eubacteria and yeasts were increased. Regardless of dose, the
      microflora returned to normal levels at day 28 (2 weeks after the administration
      of BMS-284756 was discontinued). Fecal concentrations of BMS-284756 increased
      with the higher doses, from 35.7 mg/kg (100 mg) to 262.8 mg/kg (1200 mg). These
      ecological findings should be considered if 800- or 1200-mg doses of BMS-284756
      are to be used for longer periods than 14 days. CONCLUSION: The ecological impact
      of BMS-284756 is selective, with results similar to those described for other
      quinolones.

PMID- 12047416
TI  - In vitro activities of new quinolones against Brucella melitensis isolated in a
      tertiary-care hospital in Turkey.
AB  - We have evaluated the in vitro activities of seven fluoroquinolones against 69
      strains of Brucella melitensis. According to their minimum inhibitory
      concentration for 90% growth (MIC(90)) values, the most active agent was found to
      be sparfloxacin (MIC(90) 0.12 mg/L) followed by levofloxacin, ciprofloxacin,
      ofloxacin (MIC(90) 0.50 mg/L) and grepafloxacin (MIC(90) 1 mg/L), gemifloxacin
      (MIC(90) 2 mg/L) and gatifloxacin (MIC(90) 4 mg/L).

PMID- 12047417
TI  - Clinical microbiological case: cardiac tamponade due to hemorrhagic pericarditis
      in a non-immunocompromised woman from south-eastern United States.

PMID- 12047418
TI  - Clinical microbiological case: a 22-year-old-man with fever and maculopapular
      rash.

PMID- 12047419
TI  - A case of an abscess due to Salmonella serotype enteritidis behind the eye: a
      unique event as part of a growing food-borne problem in Belgium?

PMID- 12047422
TI  - Myeloid dendritic cells make it to the top.

PMID- 12047423
TI  - Eosinophil-epithelial cell interactions: an important facet of asthmatic
      inflammation.

PMID- 12047424
TI  - Cellular mechanisms of chronic cell-mediated allergic conjunctivitis.

PMID- 12047425
TI  - Rapid response of circulating myeloid dendritic cells to inhaled allergen in
      asthmatic subjects.
AB  - BACKGROUND: Dendritic cells (DC) are thought to play a key role in the initiation
      and maintenance of T cell immunity to inhaled antigens. While the density of DC
      within the bronchial mucosa is increased in stable asthma, there is little
      information currently available concerning the effects of allergen inhalation on
      DC in subjects with asthma. OBJECTIVES: To enumerate changes in the numbers of
      circulating CD33(+) myeloid DC in asthmatics, before and after allergen
      challenge. METHODS: Blood DC numbers were enumerated by flow cytometry before and
      at 3, 6 and 24 h after inhaled allergen and diluent in 10 mild, allergic
      asthmatic subjects. RESULTS: Blood DC numbers rapidly fell from 3.42 +/- 0.30 x
      10(7)/L at baseline, to 2.10 +/- 0.17 x 10(7)/L by 3 h post-challenge (P < 0.01),
      and remained significantly below baseline values at both 6 and 24 h following
      allergen challenge. No such changes in DC numbers were noted after diluent
      challenge. A similar, early fall in circulating lymphocytes was also noted post
      allergen challenge, whereas changes in circulating eosinophil and neutrophil
      numbers occurred more slowly. CONCLUSIONS: A significant proportion of myeloid DC
      rapidly 'disappear' from the circulation following allergen inhalation,
      suggesting that margination of circulating myeloid DC, and their recruitment into
      the airway mucosa, is an important feature of the immune response to inhaled
      allergen.

PMID- 12047426
TI  - Provocation with adenosine 5'-monophosphate as a marker of inflammation in
      asthma, allergic rhinitis and chronic obstructive pulmonary disease.

PMID- 12047427
TI  - Association of body mass index with respiratory symptoms and atopy: results from
      the European Community Respiratory Health Survey.
AB  - BACKGROUND: There are several reports showing that obese adults report more
      respiratory symptoms suggestive of asthma than those who are not obese.
      OBJECTIVE: To determine the association of body mass index with respiratory
      symptoms and atopy in young adults METHOD: Information collected from 15,454
      participants in the European Community Respiratory Health Survey, a multicentre
      cross-sectional survey of young adults, was analysed to determine the association
      of body mass index with respiratory symptoms and atopy. RESULTS: Men and women
      with a body mass index of greater than 30 were at an increased risk of wheeze
      with shortness of breath compared with those with a body mass of 20-24.99 (OR in
      men 1.85, 95% confidence interval 1.41-2.42; OR in women 2.03, 95% confidence
      interval 1.59-2.58). Similar associations were observed for other symptoms
      suggestive of asthma. Body mass index was not associated with 'hayfever or nasal
      allergies', specific IgE to house dust mite, grass or cat or with total IgE in
      men or women. CONCLUSION: Reported associations of body mass index with symptoms
      suggestive of asthma are unlikely to be explained by a higher risk of atopy in
      the obese. Alternative explanations must be sought.

PMID- 12047428
TI  - Associations of Fc epsilon R1-beta polymorphisms with immunoglobin E antibody
      responses to common inhalant allergens in a rural population.
AB  - BACKGROUND: Polymorphisms within the beta subunit of the high-affinity receptor
      for IgE (Fc epsilon R1-beta ) on chromosome 11q13 have been related to atopy and
      asthma and the lymphotoxin alpha (LT alpha) gene on chromosome 6 is implicated in
      asthma. OBJECTIVE: To elucidate the association of polymorphisms in the Fc
      epsilon R1-beta and LT alpha genes to IgE responses and asthma in a family
      orientated rural population. METHODS: A total of 461 adult farmers, who
      participated in an epidemiological follow-up study on respiratory symptoms among
      farmers on the Swedish island of Gotland, were examined. The traits assessed
      included serum total IgE, IgE antibody responses to 21 common inhalant allergens
      and asthma. RESULTS: The 237G mutation was only detected in seven persons. Atopy
      was found to be associated with the RsaI-ex7 AB-genotype (OR = 1.9; P = 0.04).
      The RsaI-ex7 B allele had a significant influence on IgE responses to pollens and
      dust mites (OR = 5.5; P = 0.03 and OR = 5.2; P = 0.049, respectively). The
      influence of this allele was stronger when the association towards single dust
      mite species (Lepidoglyphus destructor) was estimated (OR = 7.1, P = 0.03) and
      the association increased even more when the major allergen of L. destructor
      (rLep d 2) was analysed (OR = 11.2, P = 0.02). These associations were
      independent of sex, age and smoking, and the estimates of RsaI-in2 independent of
      RsaI-ex7. RsaI-in2, RsaI-ex7 and LT alpha genotypes were unassociated with total
      serum IgE. No significant difference in the distribution of RsaI-in2, RsaI-ex7
      and LT alpha genotypes was found among subjects with atopy or asthma compared to
      healthy controls. CONCLUSION: This study supports the notion that polymorphisms
      in the Fc epsilon R1-beta gene have significant effects on IgE responsiveness.
      Secondly, dust mites in rural populations influence the expression of genes on
      chromosome 11q13.

PMID- 12047430
TI  - Mite avoidance can reduce air trapping and airway inflammation in allergic
      asthmatic children.
AB  - BACKGROUND: We investigated the effects of prolonged allergen avoidance in 18
      house dust mite-sensitized asthmatic children during a prolonged residential
      period at a high altitude, allergen-free environment. METHODS: Evaluations of
      residual volume (RV) and exhaled nitric oxide (eNO) were performed (i) at
      admission to the residential house in September, (ii) in December after 3 months
      of stay, (iii) in January after 15 days at home, exposed to allergens, and (iv)
      in June after 9 months of stay. RESULTS: During the study period RV showed a
      significant decrease in December (from 117.5 +/- 7.7% to 96.5 +/- 3.2%) (P <
      0.02) and a following increase in January (126.2 +/- 17.2%), after allergen re
      exposure (P < 0.03). RV decreased again in June at the end of the study period
      (91.1 +/- 6.0%) (P = 0.001). FEV(1), FEF(25-75) and VC values did not present
      significant variations. ENO showed a significant decrease in December after 3
      months at high altitude (from 21.3 +/- 3.9 p.p.b. to 11.9 +/- 1.7 p.p.b.) (P =
      0.03), but no further significant change. No correlation was found between lung
      volumes and eNO, probably reflecting different aspects of asthma. CONCLUSIONS:
      Results suggest that RV may be more sensitive than other respiratory function
      parameters in identifying children with air trapping, being influenced
      significantly as the inflammatory indices by effective allergen
      avoidance/exposure regimen.

PMID- 12047429
TI  - Prevention of sensitization to house dust mite by allergen avoidance in school
      age children: a randomized controlled study.
AB  - BACKGROUND: Sensitization to dust mites predisposes to asthma and allergic
      rhinitis, and prevention of this sensitization might reduce the rising prevalence
      of these disorders. OBJECTIVE: To test the effectiveness of dust mite avoidance
      measures on the development of sensitization to dust mites in children. METHODS:
      As part of a multicentre study (Study of Prevention of Allergy in Children of
      Europe), 242 children, aged 5-7 years, in three European countries (United
      Kingdom, Greece and Lithuania), were randomized to prophylactic group (n = 127)
      and control group (n = 115). At randomization these children were required to
      have a family history of atopy and positive skin test to an aeroallergen but not
      to house dust mite. Children in the prophylactic group were provided with dust
      mite impermeable mattress covers and advice on environmental measures to reduce
      exposure to dust-mite allergen. Control group children were given non-specific
      advice. After 12 months a standardized questionnaire was completed and skin prick
      tests were performed. RESULTS: Ten children in the prophylactic group and 19 in
      the control group were lost to follow-up. Three of 117 (2.56%) children in the
      prophylactic group and nine of 96 (9.38%) in the control group developed
      sensitization to dust mites. Logistic regression analysis confirmed an
      independent effect of prophylactic measures (adjusted odds ratio (OR): 0.14, 95%
      confidence interval (CI): 0.03-0.79, P = 0.03). Fifteen children need to be
      treated to prevent sensitization in one child. CONCLUSION: Dust mite
      sensitization can be reduced in school age children with simple mite avoidance
      measures.

PMID- 12047431
TI  - Personal exposure to house dust mite allergen in bed: nasal air sampling and
      reservoir allergen levels.
AB  - BACKGROUND: Assessment of personal exposure to dust mite allergen has relied on
      proxy measures. Only recently has a means to directly measure inhaled allergen
      particle number become available (the intra-nasal air sampler). OBJECTIVE: To
      quantify inspired dust mite group 1 and group 2 allergen-bearing particles in bed
      in undisturbed conditions prior to sleep by nasal air sampling and to investigate
      the relationship between inhaled particles and reservoir allergen levels.
      METHODS: Twelve volunteers wore nasal samplers in bed for 6 evenings, nose
      breathing in undisturbed conditions. Allergen-bearing particles ('halos') were
      detected by immunostaining for Der p 1, Der p 2, or Der p 1 and Der p 2 together,
      and counted by light microscopy. Count data were square root transformed for
      analysis of variance. Mattress dust samples were assayed for Der p 1 and Der p 2
      concentrations. RESULTS: Square root detransformed mean particle counts per 30
      min sample were: Der p 1, 4.22; Der p 2, 5.9; Der p 1 + Der p 2, 4.87; and for
      all samples, 5.01, with no difference between the groups. With replicate samples,
      halo number correlated significantly with mattress allergen concentrations (Der p
      1 r = 0.80, P < 0.01; Der p 2 r = 0.68, P < 0.02). CONCLUSION: Nasal air sampling
      can be used to quantify nocturnal Der p exposure in undisturbed conditions in an
      area with moderate exposure to mite allergen and can provide a direct measure of
      inhaled mite allergen. The choice of either Der p 1 or Der p 2 is appropriate for
      this purpose.

PMID- 12047432
TI  - Increases in collagen type I synthesis in asthma: the role of eosinophils and
      transforming growth factor-beta.
AB  - BACKGROUND: Collagen type I is one of the major deposits in thickening of the
      reticular basement membrane of asthma. OBJECTIVE AND METHODS: In this study, we
      assessed turnover of collagen type I in asthma by measuring procollagen type I C
      terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in
      induced sputum. RESULTS: PICP but not ICTP was found to be significantly higher
      in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was
      inversely correlated with %FEV(1.0) (r = -0.539), and its levels significantly
      increased upon exacerbation (P < 0.05), indicating that collagen synthesis
      increases during asthma exacerbation. Additionally, PICP was found to
      significantly correlate with eosinophil counts in sputum (r = 0.539), indicating
      that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF
      beta, a potent stimulator of collagen synthesis, we immunocytochemically examined
      TGF-beta-positive cells in sputum. TGF-beta-positive cells significantly
      correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting
      that TGF-beta released from eosinophils is involved in collagen synthesis.
      CONCLUSIONS: The results of the present study suggest that collagen synthesis is
      stimulated in asthmatic airways by eosinophils through TGF-beta, while collagen
      degradation is not, and that PICP in sputum can act as a new marker for airway
      inflammation in asthma.

PMID- 12047433
TI  - Elevated expression of interleukin-9 mRNA in the bronchial mucosa of atopic
      asthmatics and allergen-induced cutaneous late-phase reaction: relationships to
      eosinophils, mast cells and T lymphocytes.
AB  - BACKGROUND: Interleukin-9 is a T cell-derived Th2-type cytokine that has been
      linked to airway hyper-responsiveness, mucus hypersecretion and mast cell
      infiltration in animal models. We recently demonstrated the potential for IL-9 to
      act in human eosinophil development and survival. OBJECTIVES: The aims of this
      study were: (i) to compare IL-9 mRNA expression in bronchial biopsies between
      atopic asthmatics and normal controls, (ii) to investigate kinetic expression of
      IL-9 mRNA in skin biopsies after allergen challenge; and (iii) to relate IL-9
      expression to infiltration of eosinophils, mast cell and T lymphocytes in local
      tissue. METHODS: Bronchial biopsies were obtained from atopic asthmatics (n = 12)
      and normal non-asthmatics (n = 12) at baseline. Skin biopsies were obtained from
      atopic subjects (n = 11) at 1, 3, 6, 24, 48 and 72 h after allergen challenge.
      Diluent challenge sites at 24 h were used as controls. IL-9 mRNA was identified
      using the technique of in situ hybridization. The numbers of eosinophils, mast
      cells and T cells were evaluated by immunohistochemistry. RESULTS: The numbers of
      IL-9 mRNA(+) cells present in the bronchial mucosa were significantly greater in
      atopic asthmatics than those in normal controls (P = 0.003). The numbers of
      eosinophils, but not mast cells, were also significantly higher in asthmatics (P
      < 0.005). The numbers of IL-9 mRNA(+) cells present in the airway of asthmatics
      significantly correlated with the numbers of eosinophils (r = 0.623, P = 0.03),
      but not mast cells or T cells. Compared with diluent challenge, the numbers of IL
      9 mRNA(+) cells were significantly elevated at all allergen-challenged sites in
      the skin, with maximal signals at 48 h (P < 0.005). At 72 h, the numbers of IL-9
      mRNA(+) cells significantly correlated with the numbers of eosinophils (r =
      0.707, P = 0.015). CONCLUSION: Elevated expression of IL-9 in allergic
      inflammation may contribute to local eosinophil infiltration and survival in
      asthma and other allergic atopic diseases.

PMID- 12047434
TI  - Characterization of 'adult-type' mast cells derived from human bone marrow
      CD34(+) cells cultured in the presence of stem cell factor and interleukin-6.
      Interleukin-4 is not required for constitutive expression of CD54, Fc epsilon RI
      alpha and chymase, and CD13 expression is reduced during differentiation.
AB  - BACKGROUND: In vitro-derived human mast cells exhibit different properties,
      depending in part on the source of progenitor cells. Most investigations have
      used fetal liver, cord blood or peripheral blood. Few have used adult bone
      marrow. OBJECTIVE: Human mast cells derived in vitro from the CD34(+) progenitors
      in bone marrow and cord blood that had been cultured with recombinant human stem
      cell factor (rhSCF) and recombinant human interleukin-6 (rhIL-6) were compared.
      METHODS AND RESULTS: After 12 weeks of culture, nearly all of the cells were mast
      cells, and nearly all of these had cytoplasmic granules containing both tryptase
      and chymase (MCTC type), stained metachromatically with acidic toluidine blue,
      and expressed CD117 on the cell surface. Both tryptase protein and mRNA were
      detected by two weeks of culture. Chymase mRNA and protein were detected at 4
      weeks but not at 2 weeks of culture. By 12 weeks, chymase content per cell,
      measured by ELISA, was significantly higher (P < 0.05) in human bone marrow
      derived mast cells (HBMMC) (5.6 +/- 0.9 pg) than in cord blood-derived mast cells
      (CBMC) (2.4 +/- 0.9 pg), whereas histamine and tryptase levels were not
      significantly different. Of the cluster designations tested, CD29, CD49d, CD51
      and CD61 were strongly expressed on HBMMC. CD54 and Fc epsilon RI alpha also were
      expressed constitutively. Approximately half of CD34-sorted cells at day 0 were
      CD13(+) and this diminished as mast cell maturation occurred. Electron microscopy
      revealed that 12-week-old HBMMC had many secretory granules that contained
      spherical electron dense cores surrounded by electron lucent space, consistent
      with previous reports of immature MCTC cells developing in vivo. CONCLUSIONS:
      CD34(+) progenitors of human bone marrow are a rich source of mast cell
      progenitors capable of expressing granule and surface markers of mature mast
      cells in the presence of rhSCF and rhIL-6.

PMID- 12047435
TI  - Matrix metalloproteinase-2 from bronchial epithelial cells induces the
      proliferation of subepithelial fibroblasts.
AB  - BACKGROUND: In bronchial asthma, subepithelial fibrosis in the conducting airways
      is associated with increased numbers of subepithelial fibroblasts. OBJECTIVE:
      This study examined the hypothesis that MMP-2 from airway epithelial cells
      induces the proliferation of subepithelial fibroblasts. METHODS: Using primary
      bronchial epithelial cells MMP-2, MT1-MMP and TIMP-2 mRNA expression were
      assessed by Northern blotting and RT-PCR. Primary bronchial epithelial cells
      transfected with constructs encoding pro-MMP-2 and MT1-MMP (MMP-14). RESULTS:
      Transfected cells showed enhanced expression of the appropriate mRNA species by
      RT-PCR and enhanced MMP-2 or MT1-MMP activity by zymography. Active MMP-2 levels
      in epithelial supernatants were increased most by cotransfection with pro-MMP-2
      and MT1-MMP encoding constructs. By measuring tritiated thymidine incorporation,
      supernatants from transfected cells were found to enhance DNA synthesis of
      primary airway fibroblast cultures compared with controls. There was a strong
      correlation (r = 0.9, P < 0.01) between MMP-2 levels in epithelial cell
      conditioned media and fibroblast proliferation as indicated by DNA synthesis. The
      MMP inhibitor 1,10-phenanthroline attenuated the increased proliferation, while
      the addition of exogenous purified MMP-2 alone also increased fibroblast
      proliferation. CONCLUSIONS: Our results support a role for MMP-2 in mediating
      cross-talk between epithelial cells and myofibroblasts.

PMID- 12047436
TI  - Airway epithelial cells promote transmigration of eosinophils in a new three
      dimensional chemotaxis model.
AB  - BACKGROUND: Prominent infiltration of eosinophils in airway mucosa is the
      pathognomonic sign of asthma. The role of airway epithelial cells in eosinophil
      infiltration, however, has not been fully elucidated. OBJECTIVE: The aim of this
      study is to develop a new in vitro transmigration system composed of airway
      epithelial cells and extracellular matrix, and to investigate the role of airway
      epithelial cells in eosinophil infiltration. METHODS: A layer of type I collagen
      gel was formed in Netwell, and BEAS-2B bronchial epithelial cells were cultured
      on the gel. Then the wells covered with epithelial monolayer were filled with
      medium, inverted, and new upper chambers were constructed on the gel side by
      applying a ring cap. After further incubation with or without exogenous cytokines
      for 48 h, eosinophils or neutrophils were loaded in upper chambers (the gel side)
      and cells transmigrated to lower chambers (the epithelial cell side) were
      counted. Immunohistochemical analyses were also performed. RESULTS: While a
      simple collagen gel hardly promoted eosinophil migration even in the presence of
      eotaxin or RANTES, significant numbers of eosinophils migrated to lower chambers
      in the presence of the epithelial cells. Replacement of medium in the lower
      chamber (the epithelial cell side) with fresh medium, addition of exogenous
      eotaxin or RANTES in the upper chamber (the gel side), or pre-treatment of
      eosinophils with anti-CCR3 all inhibited transmigration. We found that the
      epithelial cells produced and deposited extracellular matrix proteins such as
      type IV collagen onto the type I collagen gel. Separately, we found that type IV
      collagen itself was capable of enhancing eotaxin-induced eosinophil migration in
      a standard chemotaxis assay. Neutrophils also efficiently migrated in the present
      transmigration system. Pre-treatment of epithelial cells with TNF-alpha and IL-4
      enhanced eosinophil transmigration, while that of neutrophils was enhanced by TNF
      alpha but suppressed by IL-4. CONCLUSION: By utilizing a new in vitro
      transmigration system mimicking the airway mucosa, we have demonstrated that
      airway epithelial cells play an essential role in transmigration of eosinophils
      and that multiple factors such as chemokines, extracellular matrix proteins and
      exogenous inflammatory cytokines are involved in efficient transmigration.

PMID- 12047437
TI  - Migration through basement membrane modulates eosinophil expression of CD44.
AB  - BACKGROUND: Tissue eosinophils express more membrane receptors and release more
      mediators than blood eosinophils, suggesting that migration from blood to tissue
      modulates eosinophil phenotype and functions. OBJECTIVE: We postulated that
      eosinophil passage through endothelial basement membrane, an important step of
      eosinophil migration into tissue, may be responsible for some of these changes.
      METHOD: We previously showed that 5-oxo-6, 8, 11, 14-eicosatetraenoic acid (5-oxo
      ETE) in combination with IL-5 promotes eosinophil migration through Matrigel, a
      mouse tumour cell-derived basement membrane. Using this model, we evaluated the
      effect of trans-Matrigel migration on purified human blood eosinophil expressions
      of CD44, CD69 and HLA-DR that either increase or appear on activated eosinophils,
      and releases of peroxidase (EPO), leukotriene (LT) C(4) and granulocyte-monocyte
      colony stimulating factor (GM-CSF). RESULTS: IL-5, but not 5-oxo-ETE, increased
      eosinophil expression of CD44 and CD69. Migration of eosinophils through Matrigel
      significantly increased CD44 expression level over the one induced by IL-5 (P =
      0.0001). Migration through Matrigel did not modify CD69 expression compared with
      the one obtained in the presence of IL-5 alone; however, incubation of
      eosinophils on Matrigel decreased IL-5-induced CD69 (P = 0.0001). Trans-Matrigel
      migration did not modify HLA-DR expression, nor EPO, LTC(4) and GM-CSF releases.
      CONCLUSION: These data show that in vitro trans-Matrigel migration and Matrigel
      contact modulate eosinophil membrane receptor expression. Consequently, they
      suggest that migration through basement membrane mediates changes in cell-surface
      phenotype observed on activated eosinophils and probably prepares them for
      interactions with tissue components and cells.

PMID- 12047438
TI  - Dexamethasone inhibits maturation, cytokine production and Fc epsilon RI
      expression of human cord blood-derived mast cells.
AB  - BACKGROUND: Mast cells are responsible for eliciting the early phase and for
      contributing to the development of the late phase of allergic reactions, through
      the release of cytokines and other inflammatory mediators. OBJECTIVE: To assess
      whether the glucocorticoid dexamethasone has a direct effect on mast cell
      progenitor maturation and on mature cord blood-derived mast cell properties.
      METHODS: Mast cells were obtained by culturing human umbilical cord blood
      mononuclear cells with stem cell factor, IL-6 and prostaglandin E2. Mast cell
      numbers were assessed by Toluidine Blue staining and immunocytochemistry of
      tryptase positive cells. The expression of Fc epsilon RI, CD49d and c-kit was
      assessed by flow cytometry. Histamine release was determined by a radioenzymatic
      assay. Cys-LT, GM-CSF and TNF-alpha production and release were determined by
      ELISA. RESULTS: Dexamethasone (10(-6) M-10(-9) M) time- and dose-dependently
      inhibited the maturation of the mast cell progenitors. Dexamethasone did not
      affect the basal expression of Fc epsilon RI, CD49d and c-kit, but it inhibited
      the IgE-dependent enhanced expression of Fc epsilon RI. Dexamethasone (10(-6) M
      10(-9) M) had no significant effect on Fc epsilon RI-dependent histamine release
      or the synthesis and release of Cys-LT from the mature mast cells. However, pre
      incubation of the mast cell cultures with dexamethasone for 1 h, prior to cross
      linking of Fc epsilon RI, dose-dependently inhibited the production and secretion
      of both GM-CSF and TNF-alpha. CONCLUSIONS: From these in vitro data we propose
      that glucocorticosteroids are effective drugs in the management of allergic
      inflammation due to their capacity to inhibit mast cell development, IgE
      dependent Fc epsilon RI expression and mast cell production of GM-CSF and TNF
      alpha.

PMID- 12047439
TI  - Fluticasone inhibits the progression of allergen-induced structural airway
      changes.
AB  - BACKGROUND: Inhaled corticosteroids are widely used as first-line therapy in
      patients with asthma. The concept of early introduction is more and more
      accepted. OBJECTIVE: In our rat model of airway remodelling, we investigated
      whether treatment with inhaled fluticasone propionate can inhibit further
      progression of established structural airway changes. METHODS: Sensitized Brown
      Norway rats were exposed to aerosolized ovalbumin (1%) from day 14 to 42. From
      day 28 to 42, animals were treated with inhaled fluticasone or placebo 30 min
      before each allergen challenge. One control group was exposed to PBS from day 28
      to 42, a second control group throughout the whole experiment. RESULTS: Exposure
      to ovalbumin during 2 weeks induced structural airway changes, including
      epithelial cell proliferation, increase in airway wall area and fibronectin
      deposition. Goblet cell number was increased, although not significantly compared
      with PBS. Continuing allergen exposure for 2 weeks further enhanced each of these
      features. In addition, the amount of collagen in the airway wall was enhanced by
      4 weeks allergen exposure compared with PBS-exposed animals. These additional
      increases were inhibited by treatment with fluticasone during the last 2 weeks.
      CONCLUSION: The progression of established allergen-induced structural airway
      changes in sensitized rats can be inhibited by treatment with fluticasone.

PMID- 12047440
TI  - The importance of maximal airway response to methacholine in the prediction of
      asthma development in patients with allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is a known predictor and correlate of asthma
      incidence. However, it is not clear which patients with allergic rhinitis are at
      greater risk of the development of asthma. OBJECTIVE: The aim of this study was
      to investigate whether airway hypersensitivity and/or increased maximal response
      on the dose-response curve to methacholine would predict the development of
      asthma in subjects with allergic rhinitis. METHODS: One hundred and forty-one
      children with allergic rhinitis were prospectively studied for 7 years. At the
      initiation of the study, bronchial provocation test with methacholine using a
      stepwise increasing concentration technique was performed to measure PC(20)
      (provocative concentration causing a 20% fall in FEV(1)) and maximal response.
      Each subject was evaluated at least every 6 months and details of asthmatic
      symptoms or signs experienced during the intervening period were taken. RESULTS:
      Twenty of 122 subjects available for the follow-up developed asthma. Nine (19.6%)
      of 46 hypersensitive (PC(20) < 18 mg/mL) subjects developed asthma, compared with
      11 (14.5%) of 76 normosensitive subjects (P = 0.462). Eight (32%) of 25 subjects
      without maximal response plateau developed asthma, compared with 12 (12.4%) of 97
      subjects with maximal response plateau (P = 0.018). Score test for trend revealed
      a significant association between the level of maximal response (P = 0.007), but
      not the degree of methacholine PC(20) (P = 0.123), and the future development of
      asthma. CONCLUSION: An increased maximal airway response to methacholine is shown
      to be a better predictor for the future development of asthma in patients with
      allergic rhinitis, than airway hypersensitivity to methacholine.

PMID- 12047441
TI  - A double-blind, placebo-controlled study on the diagnostic accuracy of an
      electrodermal test in allergic subjects.
AB  - BACKGROUND: Many unconventional diagnostic procedures based on bioelectrical skin
      responses are presently widely used for allergic diseases, but rigorous
      experimental evaluations of their accuracy are still lacking. AIM: We assessed
      whether an electrodermal device can correctly diagnose respiratory allergy.
      METHODS: The diagnostic accuracy of the electrodermal device was assessed in
      double-blind fashion in 72 allergic patients and 28 healthy volunteers. A random
      sequence of substances in sealed vials, including histamine, allergens,
      immunoglobulins at various dilutions and physiological saline, were tested in
      duplicate in each subject. RESULTS: A wide variability of the measurements was
      found in most patients irrespective of their allergy status and of the substance
      tested. Allergic patients showed more negative skin electrical response at the
      second trial, compared to normal controls, independent of the tested substance.
      No significant difference in skin electrical response between allergens and
      negative controls could be detected. CONCLUSION: We conclude that the studied
      bioelectrical method, under blind testing, cannot correctly detect respiratory
      allergy.

PMID- 12047442
TI  - The allergen profile of ash (Fraxinus excelsior) pollen: cross-reactivity with
      allergens from various plant species.
AB  - BACKGROUND: Ash, a wind-pollinated tree belonging to the family Oleaceae, is
      distributed world-wide and has been suggested as a potent allergen source in
      spring time. OBJECTIVE: The aim of this study was to determine the profile of
      allergen components in ash pollen in order to refine diagnosis and therapy for
      patients with sensitivity to ash pollen METHODS: The IgE reactivity profile of 40
      ash pollen-allergic patients was determined by immunoblotting. Antibodies raised
      to purified pollen allergens from tree and grass pollens were used to identify
      cross-reactive structures in ash pollen extract. IgE immunoblot inhibition
      studies were performed with recombinant and natural pollen allergens to
      characterize ash pollen allergens and to determine the degree of cross-reactivity
      between pollen allergens from ash, olive, birch, grasses and weeds. RESULTS: The
      allergen profile of ash pollen comprises Fra e 1, a major allergen related to the
      major olive allergen, Ole e 1, and to group 11 grass pollen allergens, the
      panallergen profilin, a two EF-hand calcium-binding protein, a pectinesterase
      like molecule and an allergen sharing epitopes with group 4 grass pollen
      allergens. Thus, the relevant allergens of ash are primarily allergens that share
      epitopes with pollen allergens from other tree, grass and weed species.
      CONCLUSIONS: Allergic symptoms to ash pollen can be the consequence of
      sensitization to cross-reactive allergens from other sources. The fact that ash
      pollen-allergic patients can be discriminated on the basis of their specific IgE
      reactivity profile to highly or moderately cross-reactive allergens has
      implications for the selection of appropriate forms of treatment.

PMID- 12047443
TI  - Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1.
AB  - BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to
      study the mechanisms of allergic sensitization and the development of new types
      of immunotherapy. Many of the studies require a knowledge of the T cell epitopes,
      and because Der p 1 is polymorphic, the effect of natural amino acid substitution
      in the allergen. The intranasal administration of peptides containing T cell
      epitopes can induce a mucosal tolerance but it is not known if the major activity
      is limited to stimulatory peptides and if, as found for autoimmunity, some
      epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of
      Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H
      2(q) mice and the sequences which induce tolerance by intranasal administration
      of peptides. METHODS: T cell responses of mice immunized with Der p 1 were
      measured by in vitro T cell stimulation assays so an extensive study of epitope
      recognition and intranasal tolerance could be made. Synthetic peptides were used
      to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to
      map the major H-2(b) epitope in detail. This included the effect of the common
      polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three
      and two regions, respectively, were found to contain stimulatory T cell epitopes
      for H-2(b) and H-2(q) mice. The peptides in these regions were also the most
      active at inducing intranasal tolerance for the responding haplotype. The
      correspondence between inhibitory and stimulatory peptides was maintained for the
      fine mapping of the major H-2(b) epitope. This was found about a core region of
      118-126 which was overlapping but separate to a consensus sequence for the
      binding of endogeneous peptides. Peptides with alanine at the naturally
      polymorphic residue 124 stimulated and inhibited responses to Der p 1 more
      effectively, while peptides with the valine 124 variant were immunogenic but
      poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides
      representing each of five epitopes recognized by two strains of mice were able to
      induce mucosal tolerance and the major tolerizing activity was limited to these
      epitopes. The position of the core major epitope for C57 mice, which differs from
      a previously predicted epitope, and its specificity for the natural alanine 124
      variant is described.

PMID- 12047445
TI  - Pulmonary function changes and immunomodulation of cytokine expression by
      zafirlukast after sensitization and allergen challenge in brown Norway rats.
AB  - BACKGROUND: The cysteinyl leukotrienes are known important mediators in bronchial
      asthma. OBJECTIVE: Our purpose was to evaluate the effect of zafirlukast on the
      late-phase reaction, bronchial hyper-responsiveness (BHR) and T cell-related
      cytokine mRNA expression in ovalbumin (OA)-sensitized brown Norway rats (BNRs).
      METHODS: Thirty BNRs were equally divided into three groups. Group I and II
      animals were sensitized and then provoked with OA. Zafirlukast was given
      intraperitoneally (i.p.) to group I animals prior to provocation. Group II
      animals received i.p. normal saline. Group III animals (controls) were not
      sensitized and breathed aerosolized saline. After OA provocation, the animals
      were anaesthetized. Pulmonary function tests (PFT) were performed at baseline and
      after varying doses of acetylcholine. Thereafter, bronchoalveolar lavage (BAL)
      was performed and the lungs were examined histologically. Total RNA was extracted
      from lung tissue and reverse transcriptase-polymerase chain reaction (RT-PCR) was
      performed using primers for IL-2, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IFN-gamma,
      iNOS and beta-actin. RESULTS: Group II OA-treated BNRs had worse PFT results,
      more severe bronchoconstriction in response to acetylcholine, and more severe
      inflammation in lung tissue than the other two groups. Group II had higher IL-2,
      IL-4, IL-10 and IFN-gamma cytokine levels in BAL fluid and higher IL-2, IL-4, IL
      5, IL-6, IL-10, IFN-gamma, TNF-alpha and iNOS mRNA levels when compared with
      group I. CONCLUSION: Zafirlukast is effective in preventing late-phase
      bronchoconstriction and BHR, reducing inflammatory response, and decreasing IL-2,
      IL-4, IL-5, IL-6, IL-10 and IFN-gamma and iNOS mRNA expression.

PMID- 12047444
TI  - Intranasal application of purified protein derivative suppresses the initiation
      but not the exacerbation of allergic rhinitis in mice.
AB  - BACKGROUND: Several epidemiological and experimental studies have demonstrated
      that exposure to pathogens such as those from the genus Mycobacterium leads to
      the suppression of allergic sensitization and inflammation. However, little is
      known as to whether pathogen-derived soluble antigens have the potential to
      modulate the pathogenesis of allergic rhinitis. OBJECTIVE: We sought to determine
      whether application of purified protein derivative (PPD) from Mycobacterium
      tuberculosis can suppress the initiation and/or exacerbation of allergic rhinitis
      using a recently developed murine model. METHODS: First, we investigated whether
      a single intranasal application of PPD could elicit cytokine production in the
      nose by RT-PCR. BALB/c mice were repeatedly sensitized with Schistosoma mansoni
      egg antigen (SEA) intranasally without an adjuvant. PPD was applied through
      different routes either before or after sensitization. The production of SEA
      specific antibodies, nasal eosinophilia and cytokines by nasal lymphocytes was
      compared among mice that had or had not received PPD treatment. RESULTS: IFN
      gamma, but not IL-4, was detected in the nasal tissue 12 to 48 h after a single
      intranasal application of 10 microg PPD. Repeated intranasal application of PPD
      prior to and during sensitization with SEA significantly inhibited the production
      of both SEA-specific IgE/IgG1 and nasal eosinophilia. Moreover, it partially
      inhibited the production of IL-4 by nasal lymphocytes in response to SEA.
      Conversely, this treatment led to a significant increase in IFN-gamma production.
      On the other hand, PPD applied through the footpad had no effect over the same
      period. Repeated intranasal application of PPD after sensitization with SEA had
      no exacerbative effect on allergic inflammation. CONCLUSION: These results
      indicate that the local application of PPD, and the subsequent induction of IFN
      gamma, inhibits the initiation, but not the exacerbation, of allergic rhinitis in
      mice. This suggests that pathogen-derived antigens have potential for use in the
      prevention and prophylaxis of allergic rhinitis.

PMID- 12047446
TI  - The tryptase inhibitor APC-366 reduces the acute airway response to allergen in
      pigs sensitized to Ascaris suum.
AB  - BACKGROUND: Tryptase is a mast cell serine protease that is released during mast
      cell degranulation. It has been implicated as an important enzyme in the
      pathophysiology of asthma, but its role in this disease is not fully elucidated.
      OBJECTIVE: In this study, we investigated the effects of a tryptase inhibitor,
      APC-366, on the acute allergic airway reaction in specific pathogen-free pigs
      sensitized to the antigen Ascaris suum. METHODS: APC-366 (5 mg in 1 mL of water,
      each dose) was given as an aerosol to seven pigs two times (t); at t = - 60 min
      and t = - 15 min Control pigs received water. Ascaris antigen (in 2 mL saline)
      was nebulized to the airways over approximately 5 min at t = 0. All aerosols were
      generated with an ultrasonic nebulizer. RESULTS: The allergen challenge caused an
      acute reaction with a significant increase in airway resistance (R(aw)) in the
      control pigs from 3.3 +/- 0.6 cmH20/l/s to 10.2 +/- 2.3 cmH20/l/s, while in the
      APC-366-treated pigs, the R(aw) increased from 2.6 +/- 0.4 cmH20/l/s to 4.5 +/-
      0.7 cmH20/l/s (P < 0.05 compared to controls). The dynamic lung compliance
      (C(dyn)) decreased significantly in the control pigs, but not in the APC-366
      treated animals. The histamine concentration in urine in the control pigs was
      elevated immediately after allergen challenge, while this release was markedly
      reduced in the APC-366-treated pigs. CONCLUSION: The tryptase inhibitor APC-366
      reduces the acute airway response to allergen significantly. There is also a
      reduced elevation in urine histamine concentration after challenge in the treated
      pigs, compared to controls. These results indicate that inhibition of mast cell
      tryptase might be a useful anti-allergic treatment in asthma.

PMID- 12047452
TI  - Cervicogenic headache (CEH) after whiplash injury.
AB  - The main objective of the present investigation was to search for cervicogenic
      headache (CEH) after whiplash injury. Whiplash patients (n= 587), were followed
      for a year after their emergency service consultation. A total of 222 patients
      with headache after 1 month went through interview and examinations at 6 weeks, 6
      months and 1 year. All included persons received a questionnaire after 1 year. De
      novo CEH seemed to be present in 8% at 6 weeks and in 3% at 1 year. Previous car
      accidents, pre-existing headache and neck pain were more frequent in chronic CEH
      individuals than in those in the cohort without CEH. Range of motion in the neck
      was reduced in 65% of chronic CEH individuals hours after the accident, compared
      with 41% in the cohort. Cybex inclinometer, at 6 weeks and 1 year, demonstrated
      reduced extension in the neck. CEH seems to be present after whiplash injury,
      particularly in the early phase. It seems similar to, but probably not identical
      to, non-whiplash CEH.

PMID- 12047453
TI  - A comparison of disability and psychological factors in migraine and transformed
      migraine.
AB  - The classification of patients with migraine who develop chronic daily headache
      is controversial, with some classifying such patients as 'transformed migraine'.
      We compared patients with intermittent migraine attacks and patients with
      transformed migraine in terms of mean headache intensity on days with headache,
      depression, pain-related anxiety and headache-related disability. Patients
      classified clinically as also having tension-type headache were excluded. Aside
      from the number of days with headache per month, patients with intermittent
      migraine attacks and patients with transformed migraine were very similar in
      terms of all parameters studied. Our results support the concept that these two
      headache groups are closely related.

PMID- 12047454
TI  - Changes in headache prevalence between pre-school and pre-pubertal ages.
AB  - The prevalence rates of headache in first-born children were determined at the
      ages of 6 and 12 years in over 1000 families. A headache questionnaire was mailed
      to 1132 families when the children were 6 years old, and to 1126 families when
      the children were 12 years old. Seven hundred and ninety-eight families responded
      to both questionnaires. The prevalence of headache before the 6 months preceding
      the questionnaire ('previous headache') was 19% when the children were 6 years of
      age and 31% when the children were 12 years of age. The corresponding prevalences
      of headache during the 6 months immediately proceeding the questionnaire
      ('present headache') were 16% and 19%. Variation in occurrence of headache was
      high during follow-up years. Maternal frequent headache (> or = 1/month) was
      significantly associated with the increase in prevalence of present headache in
      boys between the ages of 6 and 12 years. Frequent headache in mothers, fathers
      and siblings, and the occurrence of chronic illness, were also significantly
      associated with headache in the 12-year-old children.

PMID- 12047455
TI  - Treatment of cluster headache with topiramate: effects and side-effects in five
      patients.
AB  - We report on clinical experience with topiramate in the prophylactic treatment of
      three patients with chronic and two patients with episodic, otherwise therapy
      resistant, cluster headache. Patients were treated with daily doses of 75-200 mg
      topiramate. Topiramate was effective in three patients but proved ineffective and
      also caused intolerable side-effects in two patients. Topiramate may have
      prophylactic properties for treating cluster headache at lower doses than needed
      in epilepsy therapy, but its clinical value is limited due to central nervous
      system side-effects.

PMID- 12047456
TI  - Blood pressure behaviour in chronic daily headache.
AB  - The objective was to examine the association between high blood pressure (BP) and
      chronic daily headache using 24-h ambulatory blood pressure monitorization (24-h
      ABPM). This was a cross sectional study in an out-patient clinic. Women were
      selected among patients referred for first evaluation, 62 with chronic daily
      headache and 57 without chronic daily headache. The main outcome measures were
      mean office systolic and diastolic blood pressure (BP), mean systolic and
      diastolic daytime and night-time BP and BP load, and mean systolic and diastolic
      nocturnal fall. Office systolic BP was 138.2 mmHg for women with chronic daily
      headache and 141.7 mmHg for women without headache (P = 0.36). Office diastolic
      BP was 88.9 mmHg for women with headache and 92.7 mmHg for women without headache
      (P = 0.17). Mean daytime and mean night-time systolic BP was, respectively, 122.2
      mmHg and 108.8 mmHg for women with headache and 122.9 mmHg and 109.5 for women
      without headache (P = 0.82 and P = 0.80, respectively). Mean daytime and mean
      night-time diastolic BP was, respectively, 78.6 mmHg and 65.4 mmHg for women with
      headache and 79.9 mmHg and 67.1 mmHg for the women without headache (P = 0.80 and
      P = 0.45, respectively). There was no difference between the two groups regarding
      systolic and diastolic BP load and nocturnal systolic and diastolic fall. No
      significant difference in BP values was observed in women with chronic daily
      headache compared with women without headache using 24-h ABPM.

PMID- 12047457
TI  - Intractable eye pain: indication for triptans.
AB  - Management of pain is difficult in many eye diseases. Particularly in patients
      undergoing surgical procedures, postoperative intractable pain is a major concern
      and severely influences the patient's comfort. We present 13 patients (eight
      male, five female, mean age 36 years) in whom sumatriptan, a highly selective 5
      HT1B/1D agonist that is normally used as a specific anti-migraine drug, was used
      for the treatment of pain following photorefractive keratectomy (PRK). In two
      patients both eyes were operated on different days, resulting in a total of 15
      operated eyes. A positive clinical response was achieved in all patients. In
      particular, in four patients, who received a second dose prophylactically 4 h
      following the first dose and before the recurrence of pain, we achieved excellent
      efficacy and stable control of pain. Further controlled studies are needed to
      investigate the usefulness of 5-HT1B/1D agonists in painful eye conditions.

PMID- 12047459
TI  - Two cases of medically and surgically intractable SUNCT: a reason for caution and
      an argument for a central mechanism.
AB  - We report two cases of SUNCT that demonstrate the medically and surgically
      refractory nature of this disorder and support the hypothesis that the causative
      'lesion' lies within the central nervous system. After both patients had failed
      medical therapies, the first underwent a glycerol rhizotomy, gammaknife
      radiosurgery and microvascular decompression of the trigeminal nerve. The second
      patient underwent gammaknife radiosurgery of the trigeminal root exit zone and
      two microvascular decompression surgeries. Neither patient benefited from these
      procedures. Currently, the first patient suffers from anaesthesia dolorosa and
      the second patient from unilateral deafness, chronic vertigo and dysequilibrium
      as a result of surgical trauma. These cases of SUNCT highlight the uncertainty
      regarding the role of surgery given the potential for significant morbidity.
      These cases also suggest that SUNCT originates and may be maintained from within
      the CNS and this central locus explains why SUNCT is not typically amenable to
      interventions aimed at the peripheral portion of the trigeminal nerve.

PMID- 12047458
TI  - COX-2 inhibitor for the treatment of idiopathic stabbing headache secondary to
      cerebrovascular diseases.
AB  - The idiopathic stabbing headache (ISH) is characterized by a stabbing pain of
      short duration, variable localization and an errant evolution pattern. As its
      biological mechanisms are unknown and the treatment options are little effective,
      this disorder shows a strong impact on the patient's life. Two females and one
      male, aged 76, 66 and 72 years, respectively, started presenting ISH within 20
      days after the onset of a stroke. All the patients were treated for the ISH with
      celecoxib, a COX-2 specific inhibitor, with full recovery from ISH up to 6 days
      after it was first administered. The interruption of the drug 60 days after the
      treatment with celecoxib induced again the appearance of algic symptoms in two
      patients. We concluded that cerebrovascular diseases (CD) can lead to ISH and
      that the COX-2 inhibitor can be an effective prophylactic drug for ISH after CD.

PMID- 12047460
TI  - A negative trial of sodium valproate in cluster headache: methodological issues.
AB  - We report the result of a double-blind placebo controlled study of sodium
      valproate (SV) (1000-2000 mg/day) in the prophylaxis of cluster headache CH.
      Episodic and chronic CH were defined according to the International Headache
      Society classification. Ninety-six patients were included, 50 in the SV group and
      46 in the placebo group. After a 7-day run-in period, patients were treated for 2
      weeks. The primary efficacy criterion was the percentage of patients successfully
      improved, i.e having an at least 50% reduction in the average number of attacks
      per week between the run-in period and the last week of treatment. Whatever the
      type of CH, there was no difference between the two groups: 50% of subjects in
      the SV group and 62% in the placebo group were successfully improved (P = 0.23).
      This high success rate observed in the placebo group, which is likely to be due
      to the spontaneous remission of the episode, does not allow us to draw any valid
      conclusion with regard to the true efficacy of SV in the prophylaxis of CH.

PMID- 12047461
TI  - Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced
      doses: a comparison with propranolol 160 mg daily.
AB  - This was a phase-IV double-blind equivalence trial designed to assess the
      efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5
      mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release
      propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment
      period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly
      because of adverse events (n=58). The mean attack frequency in the double-blind
      period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for
      the propranolol group. The mean attack frequency in the last 28 days of the
      double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for
      propranolol. Both flunarizine groups were at least as effective as propranolol
      (P<0.001 in one-sided test). The percentage of responders (defined as subjects
      for whom attack frequency decreased by at least 50% compared to run-in) in the
      last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53%
      (141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis
      showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and
      showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No
      statistically significant differences between the treatment groups were found for
      any of the secondary parameters. Overall, 190 subjects reported one or more
      adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76
      (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The
      results of this equivalence trial show that 10 mg flunarizine daily with a drug
      free weekend is at least as effective as 160 mg propranolol in the prophylaxis of
      migraine for all evaluated parameters (one-sided equivalence tests) after 16
      weeks of treatment. In addition, 5 mg flunarizine proves to be at least as
      effective as 160 mg propranolol when looking at the mean attack frequency for
      both the whole double-blind period and the last 28 days of treatment. However, in
      the analysis of responders, 160 mg propranolol seems to be slightly better than 5
      mg flunarizine. In addition, no significant differences between the three
      treatments were found with regard to safety: all three treatments were generally
      well-tolerated and safe.

PMID- 12047462
TI  - Helicobacter pylori infection and migraine.
AB  - The study is aimed to ascertain whether the Helicobacter pylori (Hp) infection is
      responsible for the vulnerability to oxidative stress observed in migraineurs. Hp
      serological positivity was assessed by ELISA evaluation of specific IgA and IgG
      antibodies in 30 subjects (11 males and 19 females) suffering from migraine
      without aura during the headache-free period. The Hp infection was detected in
      16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an
      index of systemic oxidative status, was increased in migraineurs without Hp
      infection with respect to controls (P< 0.001), while no significant differences
      of TBA-RS were found in migraineurs with or without Hp infection. Unmodified
      values of plasma nitrite/nitrate concentrations, expression of systemic nitric
      oxide (NO), were obtained in migraineurs in comparison to controls indicating
      that Hp infection does not modify the plasma oxidative status and the systemic NO
      bioavailability of migraineurs. In conclusion, our results do not support any
      specific correlation between Hp infection and migraine.

PMID- 12047463
TI  - Nitroglycerin-induced activation of monoaminergic transmission in the rat.
AB  - When administered to migraine patients, nitroglycerin induces a spontaneous-like
      migraine attack, with a latency of several hours. Nitroglycerin acts directly
      and/or indirectly on the central nervous system, through the release of nitric
      oxide (NO). Systemic administration of the drug to the rat causes neuronal
      activation in selected subcortical areas, particularly in monoaminergic nuclei of
      the brainstem. In this study, we sought to investigate whether this activation
      correlates with changes in monoaminergic neurotransmission. For this purpose, we
      evaluated the tissue levels of catecholamines and serotonin in the hypothalamus,
      mesencephalon, pons and medulla of rats treated with systemic nitroglycerin or
      vehicle, at different time points (1, 2 and 4 h). We also evaluated the
      peripheral sympathetic response to the drug by measuring the concentrations of
      plasma catecholamines. Nitroglycerin caused an early (1 h) increase in cerebral
      (pons) and plasma levels of norepinephrine, followed by a delayed (4 h) decrease
      in medullary and pontine levels of serotonin. The initial noradrenergic
      activation may reflect the autonomic response to the rapid cardiovascular effects
      of the drug, while the delayed response may result from the interaction of
      nitroglycerin-released NO and 5-HT in central areas devoted to the modulation of
      nociception. These data might therefore help to clarify the mechanisms underlying
      the delayed migraine attack observed in migraine sufferers after systemic
      administration of nitroglycerin.

PMID- 12047464
TI  - Increase in meningeal blood flow by nitric oxide--interaction with calcitonin
      gene-related peptide receptor and prostaglandin synthesis inhibition.
AB  - This study addresses possible interactions of the vasodilators nitric oxide (NO),
      calcitonin gene-related peptide (CGRP) and prostaglandins, which may be
      implicated in the generation of vascular headaches. Local application of the NO
      donator diethylamine-NONOate (NONOate) to the exposed dura mater encephali of the
      rat caused dose-dependent increases in meningeal blood flow recorded by laser
      Doppler flowmetry. Pre-application of the CGRP receptor antagonist CGRP8-37
      significantly attenuated the evoked blood flow increases, while the
      cyclooxygenase inhibitors acetylsalicylic acid and metamizol were only marginally
      effective. Stimulation of rat dura mater with NONOate in vitro caused increases
      in CGRP release. NADPH-diaphorase activity indicating NO production was
      restricted to the endothelium of dural arterial vessels. We conclude that
      increases in meningeal blood flow caused by NO depend partly on the release and
      vasodilatory action of CGRP from dural afferents, while prostaglandins are not
      significantly involved.

PMID- 12047465
TI  - Hemicrania continua: comparison between two different classification systems.
AB  - Hemicrania continua is an uncommon primary headache disorder. This study of nine
      patients compares two different classification systems, proposed by Pareja et al.
      and Goadsby and Lipton. Although it seems logical to position the nosologic
      status of hemicrania continua under group 3 of the International Headache Society
      Classification, as proposed by Pareja et al., the Goadsby and Lipton
      classification is more clinically useful and should be included in future
      International Headache Society reclassification.

PMID- 12047466
TI  - Hemicrania continua with aura.
AB  - Hemicrania continua is a primary headache disorder that is characterized by a
      continuous unilateral headache of moderate severity, exacerbations of severe pain
      and complete responsiveness to indomethacin. We report four patients with a
      unique variant of hemicrania continua: visual auras that precede or accompany the
      pain exacerbations.

PMID- 12047467
TI  - Gabapentin (neuronetin) in the treatment of SUNCT syndrome.

PMID- 12047468
TI  - Consensus on sentinel node biopsy.

PMID- 12047469
TI  - Ductal carcinoma in situ of the breast: a comparative analysis of histology,
      nuclear area, ploidy, and neovascularization provides differentiation between low
      and high-grade tumors.
AB  - Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions that has been
      subdivided into three types: well differentiated (grade I), moderately
      differentiated (grade II), and poorly differentiated (grade III). Forty-five
      cases of DCIS were analyzed for image analysis: nuclear area, DNA ploidy, and
      vascularization in order to establish a more precise correlation between the
      histologic grade and these morphometric parameters. Our results confirm that the
      mean nuclear area, DNA ploidy, and microvessel density (MVD) progressively
      increased from DCIS grade I to DCIS grade III. The analysis of the nuclear area
      in relationship to DCIS grading demonstrated a progressive increase of values
      between grades I/II to grade III, but these data have no statistical
      significance. An analysis of DNA ploidy demonstrated significant differences
      between grades I/III (p < 0.05), but there was no statistical significance
      between grades I/II, grades II/III, or both (p > 0.005). The analysis of MVD was
      extremely significant between grades I/III (p < 0.001) and grades II/III (p <
      0.001), but between grades I/II, these values showed no significant differences
      (p > 0.05). Based on this study, it can be concluded that image analysis
      techniques confirm how DCIS presents morphometric values that increase from DCIS
      grade I to DCIS grade III and that within this spectrum, DCIS grade III can be
      identified as a group of tumors presenting a large nuclear area, aneuploid DNA,
      and abundant vascular neogenesis, confirming that this neoplasm displays more
      aggressive patterns than the other two types. These criteria should justify a
      higher rate of tumor progression to DCIS grade III.

PMID- 12047470
TI  - Occult contralateral breast carcinoma incidentally detected by breast magnetic
      resonance imaging.
AB  - The incidence of synchronous bilateral breast cancers has been reported to be
      between 3.4% and 7.4%, as detected on mammography, physical examination, or both.
      We undertook a study to determine how often magnetic resonance (MR) imaging
      detects a contralateral abnormality in patients with known breast carcinoma. As
      part of an institutional review board (IRB) -approved research protocol, 17
      patients with pathologically proven invasive carcinoma underwent preoperative MR
      imaging of both breasts using a T1-weighted, high-resolution gradient echo
      sequence (precontrast and postcontrast), an echo-planar sequence during
      administration of gadolinium, and a T2-weighted, fast-spin echo sequence. The
      morphology and dynamic enhancement of lesions in both breasts were assessed.
      Biopsy was recommended for any lesion meeting set criteria. MR imaging identified
      all 17 known invasive cancers in the breast of concern on mammography or physical
      examination. Five of 17 patients (29%) had 10 contralateral lesions identified on
      MR, for which biopsy was recommended. One of these lesions proved to represent a
      fibroadenoma. The other 9 lesions proved to represent a malignancy (6 invasive
      lobular, 2 infiltrating ductal, and 1 tubular). Four of the 17 patients (24%)
      with invasive cancer had contralateral synchronous cancers occult to physical
      examination, mammography, and ultrasonography. In this series, breast MR imaging
      of the breasts was more sensitive than mammography or physical examination in the
      detection of early breast cancer. Breast MR imaging of the contralateral breast
      may be of value as a routine screen in those patients with a known or suspected
      malignancy.

PMID- 12047471
TI  - Acute and subacute toxicity associated with concurrent adjuvant radiation therapy
      and paclitaxel in primary breast cancer therapy.
AB  - The purpose of this study was to describe the toxicity of concurrent standard
      dose adjuvant radiation therapy (RT) and paclitaxel in a series of patients
      receiving primary breast cancer therapy. From June 1998 to April 1999, 20
      patients with breast cancer received concurrent adjuvant radiation and
      paclitaxel. There were 16 patients (80%) with American Joint Committee on Cancer
      (AJCC) stage II disease and 4 with stage III disease. Eighteen patients, 12
      postmastectomy and 6 breast conservation, were treated with definitive surgery
      followed by concurrent RT and paclitaxel. Two received concurrent neoadjuvant
      radiation and paclitaxel. All patients received a doxorubicin-containing
      combination prior to radiation and paclitaxel. RT was delivered concurrently with
      paclitaxel after the completion of all doxorubicin therapy, with all patients
      receiving at least two cycles of paclitaxel (175 mg/m2) every 3 weeks during RT.
      Toxicity was graded weekly according to Radiation Therapy Oncology Group
      criteria. Thirteen patients (65%) developed grade 2 or higher cutaneous toxicity.
      In the postmastectomy group, 6 of 12 patients (50%) developed grade 2 cutaneous
      toxicity, and 4 of 12 patients (33%) developed grade 3. RT was discontinued in 1
      and placed on hold in 3 of these patients. In the breast-conservation group, 2 of
      6 patients (33%) developed grade 3 toxicity. In the neoadjuvant group, 1 of 2
      patients (50%) developed grade 3 toxicity. Four patients (20%) developed
      radiation pneumonitis, 2 of 12 (17%) in the postmastectomy group and 2 of 6 (33%)
      in the breast conservation group, with 2 requiring hospitalization and 1 a
      diagnostic open-lung biopsy. In this group of patients, standard dose concurrent
      radiation and paclitaxel resulted in a high incidence of cutaneous and pulmonary
      toxicity. Concurrent radiation and paclitaxel with these doses and schedule
      should be approached cautiously until further studies documenting its safety are
      completed.

PMID- 12047472
TI  - Lumpectomy and breast radiotherapy in breast cancer patients with a family
      history of breast cancer, ovarian cancer, or both.
AB  - This article presents an outcomes review of breast cancer patients identified
      from the cancer registries of four area hospitals. These patients had family
      histories of breast cancer, ovarian carcinoma, or both and were treated with
      conservative surgery and radiation to the involved breast. Patients were as
      follows: group 1, one first-degree relative ( n = 165, one synchronous bilateral
      breast cancer); group 2, > or =2 first-degree relatives ( n = 21); group 3, one
      second-degree relative ( n = 20); and group 4, > or =2 second-degree relatives (
      n = 18). The total of patients and breast cancer events was 224 and 225,
      respectively. Group 5 was a subgroup of 53 patients with a substantial risk
      (>10%) of a BRCA1 or BRCA2 mutation. After a median follow-up of 3.9 years, 5
      patients had local failure (2%), and 5 developed a contralateral breast cancer
      (2%). There were no significant differences in local failure rates between groups
      (p = 1.0): group 1, 5 of 166 (3%); group 2, 0 of 21 (0%); group 3, 0 of 20 (0%);
      and group 4, 0 of 18 (0%). Local failure for group 5 was 2% (1 of 53). Four of
      143 patients (3%) with a minimum 3 years of follow-up (median, 5.6 years) had
      local failure, and 5 (4%) developed a contralateral breast cancer. A univariate
      analysis was statistically significant for differentiation only (well, 0 of 67;
      moderately, 1 of 57 [1.8%]; poor, 3 of 26 [11.5%], p = 0.008). Overall survival
      for groups 1-4 did not differ significantly. Although follow-up has been
      relatively short, we have not found that breast cancer patients with various
      degrees of family histories of breast/ovarian carcinoma have had a detrimental
      outcome when treated with conservative therapy.

PMID- 12047473
TI  - Benign-appearing mammographic abnormalities in women aged 40-49.
AB  - The ongoing debate was addressed concerning the appropriateness of mammographic
      screening for women aged 40-49 years, with particular emphasis on those patients
      with benign-appearing mammographic abnormalities (BMA), and whether findings
      differed from those of successive age decades. A review was conducted of 2,482
      patients presenting for surgical consultation with a mammographic abnormality as
      a chief complaint, with particular emphasis on the 1,632 patients with BMA and
      more specifically those aged 40-49 years. Surgical interventions and risk factors
      for breast cancer were evaluated. Although 16% of 393 patients with BMAs biopsied
      were proven to have breast cancer, only 2.7% of all patients with BMAs were found
      to have breast cancer as a result of biopsy or short-term follow-up. Women aged
      40-49 years represented 48% of patients with BMAs, and only 1.5% of these
      patients had breast cancer. The finding of breast cancer in the BMA population
      was progressive by decade of age, as would be expected, and in a cut-point
      analysis of those biopsied, age 60 best divided patients into high- and low-risk
      groups. Women aged 40-49 years with BMAs should not be excluded from mammographic
      screening, as they represented part of a continuum when successive decades were
      compared. Efforts should be directed at minimizing patient and physician
      anxieties as well as diagnostic interventions related to a BMAs.

PMID- 12047474
TI  - Gemcitabine and vinorelbine combination in patients with metastatic breast
      cancer.
AB  - Both gemcitabine and vinorelbine as single agents have significant activity
      against metastatic breast cancer, with an overall response rate ranging from 14%
      to 40%. Because each drug has different mechanisms of action and toxicity
      profile, we have evaluated the activity and tolerability as a combined regimen in
      metastatic breast cancer patients. Thirty-two breast cancer patients with prior
      chemotherapy for metastatic disease received a combination of gemcitabine and
      vinorelbine at 1,200 and 30 mg/m2, respectively. The drugs were administered on
      days 1 and 8 of every 21-day cycle. The study was designed to evaluate the
      response rate, the duration of response, the time to progression, and overall
      survival. Toxicity and tolerability of this combination were also evaluated. Out
      of 32 patients analyzed, a complete response was achieved in 2 patients (6.3%)
      and a partial response in 12 patients (37.5%), with an overall response rate of
      43.8%. After a median follow-up of 7 months, the median duration of response was
      5.3 months, and the time to progression was 5.0 months. Overall survival was not
      reached because the majority of the patients were alive at the time of analysis.
      The gemcitabine and vinorelbine combination was tolerable, with hematologic
      toxicity being the most common side-effect. Three patients suffered from grade 4
      neutropenia, and none suffered from grade 4 thrombocytopenia. Nonhematologic
      toxicity was minimal and transient, with nausea and phlebitis being the most
      common. The gemcitabine and vinorelbine combination at the previously specified
      doses shows significant activity in metastatic breast cancer patients. The
      treatment is well tolerated and has an acceptable toxicity profile. In patients
      previously treated with anthracyclines and taxanes, this combination regimen
      offers an alternative treatment with preservation of a good quality of life.

PMID- 12047475
TI  - Cyclosporine and the development of multiple mammary nodules.
AB  - We report here the case of an immunosuppressed patient who developed multiple
      nodules in both breasts while on cyclosporine therapy. In this case, the benign
      appearance on imaging and benign clinical course made possible conservative
      management, thus avoiding invasive diagnostic procedures. For evaluation of these
      nodes, after cyclosporine was discontinued, the nodules involuted.

PMID- 12047476
TI  - Mucinous breast cancer and ovarian thecofibroma: case report.

PMID- 12047477
TI  - Radiological appearances of mammary angiolipoma.

PMID- 12047481
TI  - Dose-dependent increase of saquinavir bioavailability by the pharmaceutic aid
      cremophor EL.
AB  - AIMS: Bioavailability of orally administered drugs depends on several factors
      including active excretion, e.g. by P-glycoprotein (PGP), and presystemic
      metabolism, e.g. by cytochrome P450 3A (CYP3A), in both gastrointestinal tract
      and liver. Many drugs including saquinavir are substrates of both PGP and CYP3A.
      It was the aim of this study to test whether the extremely low bioavailability of
      saquinavir can be increased dose-dependently in vivo by cremophor EL, an
      'inactive' pharmaceutic aid known to inhibit PGP in vitro. METHODS: In a
      randomized, placebo-controlled, double-blind, four phase cross-over design single
      doses of oral saquinavir (Invirase, 600 mg, without food) were administered with
      increasing single doses of oral cremophor EL (up to 5000 mg) to eight healthy,
      male individuals. Saquinavir plasma concentrations were determined by LC/MS/MS up
      to 48 h after intake. Main outcome measures were area under the plasma
      concentration time curve (AUC), peak concentration (Cmax), time to reach Cmax
      (tmax) and terminal elimination half-life (t(1/2)). RESULTS: Cremophor EL dose
      dependently increased Cmax, AUC(0,4 h), and AUC(0,infinity) of saquinavir. As
      compared with placebo, the increment observed after 5000 mg cremophor EL was 13
      fold for both Cmax and AUC(0,4 h) and 5-fold for AUC(0,infinity). The terminal
      half-life and the time to reach Cmax (tmax) were unchanged. CONCLUSIONS:
      Cremophor EL increased the systemic availability of saquinavir without affecting
      its elimination suggesting that cremophor EL is not devoid of pharmacological
      action and acts as a modulator of the absorption process, probably by inhibiting
      intestinal PGP.

PMID- 12047482
TI  - The effect of food on the pharmacokinetics of nifedipine in two slow release
      formulations: pronounced lag-time after a high fat breakfast.
AB  - AIMS: The aim of this study was to investigate the effect of concomitant food
      intake on the bioavailability of two nifedipine containing modified release
      dosage forms for once daily administration. The clinical study was performed to
      investigate the in vivo relevance of pH-dependent differences in the in vitro
      release properties of the two dosage forms. METHODS: This was a randomized, open,
      4-way crossover study in 24 healthy, male subjects. Following an overnight fast
      of 12 h single doses of Adalat OROS or Slofedipine XL were administered either in
      the fasted state or immediately after a high fat American breakfast. Nifedipine
      plasma concentrations in samples obtained until 48 h after drug administration
      were determined using a validated LC-MS/MS method. Calculation of pharmacokinetic
      parameters was conducted model-independently. The two dosage forms as well as the
      two administration conditions were compared by calculating point estimates and
      90% confidence intervals for the relevant pharmacokinetic parameters. In vitro
      dissolution tests were performed using a paddle apparatus 3 acc. USP, a
      pharmacopoeial dissolution system consisting of reciprocating cylinders in flat
      bottomed glass vessels, with various buffer systems covering the entire
      physiological pH-range of the gastrointestinal tract. RESULTS: After fasted
      administration the extent of bioavailability of nifedipine as characterized by
      AUC(0,infinity) was slightly lower for Slofedipine XL compared with Adalat OROS
      with a point estimate of 82.3% primarily resulting from pronounced differences in
      nifedipine concentrations during the first 15 h after administration.
      Accordingly, maximum plasma concentrations were lower after administration of
      Slofedipine XL compared with Adalat OROS (point estimate: 84.3%). Under fed
      conditions the differences in bioavailability between the two products as
      characterized by the pharmacokinetic parameters AUC(0,tn) and Cmax were greater
      than after fasting conditions with point estimates of 69.6% and 81.0%,
      respectively. However, most striking was a pronounced delay in nifedipine
      absorption observed under fed conditions after administration of Slofedipine XL
      which resulted in lag-times of more than 15 h in 15 out of 24 subjects. Owing to
      this lag-time under fed conditions the relative bioavailability of nifedipine
      from Slofedipine XL compared with Adalat OROS was only 28% over the intended
      dosing interval of 24 h. CONCLUSIONS: In this study a dosage form-dependent food
      interaction was observed which, under fed conditions, resulted in pronounced
      differences in the relative bioavailability of nifedipine between Slofedipine XL
      and Adalat OROS over the intended dosing interval of 24 h. The delay in
      nifedipine absorption when Slofedipine XL is administered after a high-fat
      breakfast may be explained by the formulation properties. Slofedipine XL is an
      erosive tablet with an acid resistant coating whereas Adalat OROS is designed
      with an osmotic push-pull system. Under fed conditions drug from the single unit
      enteric coated dosage form exhibits a delayed absorption probably due to an
      extensively prolonged gastric residence time which does not allow drug release,
      on the other hand the osmotically driven push-pull system is not sensitive to
      concomitant food intake. The observed phenomenon might be of therapeutic
      relevance. For example a change from taking Slofedipine XL in the fed to the
      fasted state might result in increased systemic concentrations of nifedipine.

PMID- 12047483
TI  - Single- and multiple-dose pharmacokinetics of bosentan and its interaction with
      ketoconazole.
AB  - AIMS: The present study was conducted to characterize the single- and multiple
      dose pharmacokinetics of bosentan, a dual endothelin receptor antagonist, and to
      investigate a possible pharmacokinetic interaction with ketoconazole. METHODS: In
      a randomized, two-way crossover study, 10 healthy male subjects received
      treatments A and B. Treatment A consisted of a single dose of 62.5 mg bosentan on
      day 1 followed by 62.5 mg twice daily for 5.5 days. Treatment B consisted of
      bosentan (62.5 mg twice daily) for 5.5 days plus concomitant ketoconazole (200 mg
      once daily) for 6 days. Plasma concentrations of bosentan and its three
      metabolites were measured on days 1 and 7 of treatment A and on day 6 of
      treatment B. RESULTS: Bosentan was absorbed and eliminated with a tmax of 4.5 h
      (range 3.5-6.0 h) and a t(1/2) of 5.4 h (95% CI; 4.5, 6.6). Upon multiple dosing,
      the exposure to bosentan was reduced by 33% without change in tmax and t(1/2).
      Concomitant administration of ketoconazole increased the Cmax and AUC of bosentan
      2.1- (95% CI; 1.5, 2.7) and 2.3-fold (95% CI; 1.8, 2.9), respectively. Exposure
      to the metabolites was low and represented less than 25% of that to bosentan both
      after single and multiple doses. In the presence of ketoconazole, formation of
      the metabolites was inhibited. DISCUSSION: The multiple-dose pharmacokinetics of
      bosentan are consistent with the phenomenon of auto-induction. In the presence of
      CYP3A4 inhibitors, bosentan concentrations may be increased 2-fold.

PMID- 12047480
TI  - Invasive assessment of the coronary circulation: intravascular ultrasound and
      Doppler.

PMID- 12047484
TI  - Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19,
      CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian population.
AB  - AIMS: The goal of this study was to determine the frequencies of important
      allelic variants of CYP2C9, CYP2C19, CYP2E1 and DPYD in the Egyptian population
      and compare them with the frequencies in other ethnic populations. METHODS:
      Genotyping of CYP2C9 (*2 and *3), CYP2C19 (*2 and *3), c2 variant of CYP2E1 and
      DPYD alleles (*2 A-*6 ) was carried out in a total of 247 unrelated Egyptian
      subjects. An allele-specific fluorogenic 5' nuclease chain reaction assay was
      applied for detection of CYP2C9 and CYP2C19 variants. Other variants of the
      CYP2E1 and DPYD genes were determined using polymerase chain reaction (PCR)
      restriction fragment length polymorphism and allele-specific PCR based assays.
      RESULTS: CYP2C9 allele frequencies in 247 Egyptian subjects were 0.820 for
      CYP2C9*1, 0.120 for CYP2C9*2 and 0.060 for CYP2C9*3. For CYP2C19, the frequencies
      of the wild type (CYP2C19*1) and the nonfunctional (*2 and *3) alleles were
      0.888, 0.110 and 0.002, respectively. CYP2C19*3, which is considered an Asian
      mutation, was detected in one subject (0.40%) who was heterozygous (*1/*3). Two
      subjects (0.80%) were homozygous for *2/*2, while no compound heterozygotes
      (*2/*3) or homozygotes for *3 were detected. For CYP2E1, only four subjects
      (1.70%) had the rare c2 variant, expressed heterozygously, giving an allele
      frequency of 0.009. Five variants of DPYD were analysed, with no splice sites (*2
      A) or DeltaC1897 (*3) found in this population. The frequencies of other variants
      were 0.028, 0.115 and 0.090 for *4, *5 and *6, respectively. CONCLUSIONS:
      Comparing our data with that obtained in several Caucasian, African-American and
      Asian populations, we found that Egyptians resemble Caucasians with regard to
      allelic frequencies of the tested variants of CYP2C9, CYP2C19, CYP2E1 and DPYD.
      Our results may help in better understanding the molecular basis underlying
      ethnic differences in drug response, and contribute to improved individualization
      of drug therapy in the Egyptian population.

PMID- 12047485
TI  - Assessment of the effect of dextromethorphan and ketamine on the acute
      nociceptive threshold and wind-up of the second pain response in healthy male
      volunteers.
AB  - AIMS: The aim of this study was to assess the efficacy of dextromethorphan and
      ketamine relative to placebo on the acute nociceptive threshold and wind-up of
      second pain response in healthy male volunteers. METHODS: The trial was a
      randomized, double-blind, placebo-controlled, three period crossover, double
      dummy design in 12 healthy male volunteers. During each of the three periods
      (which were separated by a 1 week washout period) each volunteer received either
      a single oral dose of 0.7 mg kg(-1) dextromethorphan and placebo to ketamine, or
      placebo to dextromethorphan followed by a single intravenous injection of 0.375
      mg kg(-1) ketamine, or placebo to both dextromethorphan and ketamine. The trial
      did not schedule administration of both ketamine and dextromethorphan together.
      Acute nociceptive thresholds and wind-up of second pain were measured in the skin
      of the thenar eminence of the ventral surfaces of the right and left hands, using
      a SOMEDIC thermotest apparatus, before and at the estimated tmax for
      dextromethorphan (i.e. 2.15 h). Blood pressure and heart rate were also monitored
      before dosing and after the dosing regimen. RESULTS: Neither dextromethorphan nor
      ketamine had any significant effect on acute nociceptive thresholds on either
      hand (P>0.05). Moreover, dextromethorphan was without any significant effect
      (P>0.05) on the wind-up of the second pain response on either hand. The lsmean
      number of stimuli tolerated vs placebo (95% confidence intervals of the
      difference in number of stimuli in parentheses) were 15.84 vs 16.48 (-5.52, 4.24)
      and 11.75 vs 15.25 (-11.89, 4.90) for left- and right-hand, respectively,
      following dextromethorphan administration. In contrast ketamine produced
      significant reductions in wind-up to second pain in both the left and right hands
      (P=0.0002 and 0.0386, respectively). The lsmean numbers of stimuli tolerated vs
      placebo (95% confidence intervals of the difference in number of stimuli in
      parentheses) were 28.41 vs 16.48 (6.60, 17.25) and 25.00 vs 15.25 (0.58, 18.93)
      for left- and right-hand, respectively. CONCLUSIONS: Wind-up of second pain
      induced by noxious heat is sensitive to intervention by ketamine, which is known
      to block the NMDA receptor. These data infer that the wind-up phenomenon evoked
      by noxious heat involves the activation of NMDA receptors. This volunteer model
      of pain may have utility in the evaluation of agents that modulate their
      antinociceptive actions via NMDA mechanisms.

PMID- 12047486
TI  - Topographic pharmaco-EEG mapping of the effects of the South American
      psychoactive beverage ayahuasca in healthy volunteers.
AB  - AIMS: Ayahuasca is a traditional South American psychoactive beverage used in
      Amazonian shamanism, and in the religious ceremonies of Brazilian-based syncretic
      religious groups with followers in the US and several European countries. This
      tea contains measurable amounts of the psychotropic indole N,N-dimethyltryptamine
      (DMT), and beta-carboline alkaloids with MAO-inhibiting properties. In a previous
      report we described a profile of stimulant and psychedelic effects for ayahuasca
      as measured by subjective report self-assessment instruments. In the present
      study the cerebral bioavailability and time-course of effects of ayahuasca were
      assessed in humans by means of topographic quantitative-electroencephalography (q
      EEG), a noninvasive method measuring drug-induced variations in brain electrical
      activity. METHODS: Two doses (one low and one high) of encapsulated freeze-dried
      ayahuasca, equivalent to 0.6 and 0.85 mg DMT kg(-1) body weight, were
      administered to 18 healthy volunteers with previous experience in psychedelic
      drug use in a double-blind crossover placebo-controlled clinical trial. Nineteen
      lead recordings were undertaken from baseline to 8 h after administration.
      Subjective effects were measured by means of the Hallucinogen Rating Scale (HRS).
      RESULTS: Ayahuasca induced a pattern of psychoactive effects which resulted in
      significant dose-dependent increases in all subscales of the HRS, and in
      significant and dose-dependent modifications of brain electrical activity.
      Absolute power decreased in all frequency bands, most prominently in the theta
      band. Mean absolute power decreases (95% CI) at a representative lead (P3) 90 min
      after the high dose were -20.20+/-15.23 microV2 and -2.70+/-2.21 microV2 for
      total power and theta power, respectively. Relative power decreased in the delta
      (-1.20+/-1.31% after 120 min at P3) and theta (-3.30+/-2.59% after 120 min at P3)
      bands, and increased in the beta band, most prominently in the faster beta-3
      (1.00+/-0.88% after 90 min at P3) and beta-4 (0.30+/-0.24% after 90 min at P3)
      subbands. Finally, an increase was also seen for the centroid of the total
      activity and its deviation. EEG modifications began as early as 15-30 min,
      reached a peak between 45 and 120 min and decreased thereafter to return to
      baseline levels at 4-6 h after administration. CONCLUSIONS: The central effects
      of ayahuasca could be objectively measured by means of q-EEG, showing a time
      pattern which closely paralleled that of previously reported subjective effects.
      The modifications seen for the individual q-EEG variables were in line with those
      previously described for other serotonergic psychedelics and share some features
      with the profile of effects shown by pro-serotonergic and pro-dopaminergic drugs.
      The q-EEG profile supports the role of 5-HT2 and dopamine D2-receptor agonism in
      mediating the effects of ayahuasca on the central nervous system.

PMID- 12047488
TI  - Clinical risk factors for venous thromboembolus in users of the combined oral
      contraceptive pill.
AB  - AIMS: To estimate the risk of venous thromboembolism among women prescribed the
      oral contraceptive pill who have acute clinical conditions such as lower limb
      fractures, compared with women with idiopathic venous thromboembolism. METHODS: A
      nested case-control analysis using the General Practice Research Database,
      January 1993 to December 1999 was carried out. The participants were women aged
      15-39 years, prescribed third generation oral contraceptives (gestodene and
      desogestrel) or oral contraceptives containing levonorgestrel. The main outcome
      measures were odds ratios as a measure of the relative risk estimate for venous
      thromboembolism in women with clinical conditions that predispose to VTE.
      RESULTS: The adjusted relative risk estimate for venous thromboembolism among
      patients with the acute clinical conditions, compared with those without such
      illness, and adjusted for oral contraceptive use, was 17 (95% CI 6.5, 46).
      CONCLUSIONS: This paper documents the strong independent association between
      certain acute clinical conditions and venous thromboembolism in women prescribed
      oral contraceptives. Failure to accurately identify and exclude such patients
      from a study of the effect of oral contraceptives on the risk of venous
      thromboembolism would result in an underestimate of the risk of venous
      thromboembolism associated with oral contraceptives.

PMID- 12047487
TI  - Analgesic efficacy of sustained release paracetamol in patients with
      osteoarthritis of the knee.
AB  - AIMS: Paracetamol is widely recommended as the initial treatment for pain
      associated with osteoarthritis (OA). A sustained release (SR) paracetamol
      formulation (Panadol Extend) was compared with standard immediate release (IR)
      paracetamol (Panadol) in patients with knee pain secondary to OA. The primary
      parameter for assessment of efficacy was patient-assessed global pain relief as
      determined on day 8 of the treatment period. METHODS: A double-blind, double
      dummy, randomized study was conducted. Patients (n=403) were treated for 7 days
      with paracetamol 4 g day(-1) (SR paracetamol, two 665 mg tablets taken three
      times daily; IR paracetamol, two 500 mg tablets taken four times daily). Patients
      completed daily pain measurements and assessed global pain relief at the end of
      the study. Therapeutic noninferiority was defined on the basis of achieving
      statistical noninferiority for global pain relief. RESULTS: Analysis of the
      primary parameter for the intention to treat population showed that the
      difference in proportion of patients (SR-IR paracetamol) achieving a successful
      response on day 8 was -0.7%; 90% CI (-8.82%, 7.45%), P=0.890. For the per
      protocol population the difference in proportion was -3.0%; 90% CI (-11.61%,
      5.66%), P=0.571. As the lower bound of the 90% CI for the treatment difference in
      each case was greater than the prespecified value (-15%), SR paracetamol was
      considered to be statistically noninferior to IR paracetamol in terms of pain
      relief. The treatments were not significantly different for any of the secondary
      parameters in either populations. CONCLUSIONS: SR paracetamol taken three times
      daily was statistically and therapeutically noninferior to IR paracetamol taken
      four times daily in patients with knee pain due to OA. SR paracetamol may be more
      convenient for patients with chronic pain and has the potential to enhance
      compliance and therefore pain relief.

PMID- 12047489
TI  - Effects of oral monosodium (L)-glutamate on insulin secretion and glucose
      tolerance in healthy volunteers.
AB  - AIMS: To investigate the effects of glutamate on insulin secretion and glucose
      tolerance in humans. METHODS: Monosodium (L)-glutamate (10 g) was given orally in
      a double-blind placebo-controlled cross-over study to 18 healthy volunteers, aged
      19-28 years, with an oral (75 g) glucose load. RESULTS: The 75 min insulin
      response (AUC(0,75 min)), up to tmax of glutamate kinetics, was significantly
      correlated with the AUC(0,75 min) of glutamate concentrations (r=0.485, P=0.049).
      Glucose tolerance was not affected. CONCLUSIONS: Oral (L)-glutamate enhances
      glucose-induced insulin secretion in healthy volunteers in a concentration
      dependent manner.

PMID- 12047490
TI  - A comparison of the effects of nabumetone vs meloxicam on serum thromboxane B2
      and platelet function in healthy volunteers.
AB  - AIMS: To compare the effects of nabumetone and meloxicam, two cyclo-oxygenase-2
      (COX-2) preferential nonsteroidal anti-inflammatory drugs (NSAIDs), on platelet
      COX-1 activity and platelet function. METHODS: Twelve healthy volunteers (3 male,
      9 female, median age 22 years) participated in an open, randomized, cross-over
      trial of nabumetone 1000 mg twice daily vs meloxicam 7.5 mg twice daily during 1
      week with 2 weeks wash-out. After a second 2 week wash-out period, one dose of
      indomethacin 50 mg was given as a positive control to check for NSAID induced
      inhibition of platelet function. COX-1 inhibition was measured as percentage
      inhibition of serum TXB2 generation in clotting whole blood, and as closure time
      with use of the platelet function analyser PFA-100. Data are reported as median
      with range. Paired variables were analysed using Wilcoxons signed rank test.
      RESULTS: TXB2 levels decreased significantly after all three medications, but
      percentage inhibition after nabumetone and indomethacin (88% and 97%,
      respectively) was significantly higher than after meloxicam (63%) (P<0.05).
      Closure times increased significantly after administration of all three
      medications (P<0.05). Increases in closure time after administration did not
      differ between nabumetone and meloxicam (24% and 14%, respectively), but were
      significantly larger after indomethacin administration (63%) (P<0.01).
      CONCLUSIONS: In the maximum registered dosage, nabumetone inhibits thromboxane
      production much more than meloxicam, signifying less COX-2 selectivity of the
      former. However, both nabumetone and meloxicam cause only minor impairment in
      platelet function in comparison with indomethacin and the difference between them
      is not significant.

PMID- 12047491
TI  - Ethical issues in bipolar disorders pedigree research: privacy concerns, informed
      consent, and grounds for waiver.
AB  - Focusing on bipolar disorders research, this article considers ethical issues of
      informed consent and privacy arising in genetic pedigree research at two stages:
      the construction of tentative pedigrees to determine family eligibility for study
      and, subsequently, the enrollment of subjects in and conduct of the family study.
      Increasing concern to protect the privacy of family members of primary subjects
      or probands, following ethical controversy over a survey study at Virginia
      Commonwealth University, has led some researchers and Institutional Review Boards
      (IRBs) to apply informed consent requirements to those represented on a tentative
      pedigree at the initial stage of research. This article analyzes the possible
      benefits, risks, and burdens to prospective subjects of seeking prospective
      consent for pedigree construction at this initial stage. It argues that the
      likely risk-benefit ratio favors granting a waiver of consent requirements for
      this stage of pedigree research and presents grounds for IRBs to grant such a
      waiver. The article closes by considering particular ethical concerns that should
      be addressed in the informed consent discussion when enrolling subjects in
      pedigree studies of bipolar disorder, including concerns about subjects'
      competence to consent, management of interim and incidental findings, and issues
      particular to psychiatric research.

PMID- 12047492
TI  - Regulation of adult hippocampal neurogenesis - implications for novel theories of
      major depression.
AB  - Major depression, whose biological origins have been difficult to grasp for
      decades, might result from a disturbance in neuronal plasticity. New theories
      begin to consider a fundamental role of adult hippocampal neurogenesis in this
      loss of plasticity. Could depression and other mood disorders therefore be 'stem
      cell disorders'? In this review, the potential role of adult hippocampal
      neurogenesis and of neuronal stem or progenitor cells in depression is discussed
      with regard to those aspects that are brought up by recent research on how adult
      hippocampal neurogenesis is regulated. What is known about this regulation today
      are mosaic pieces and indicates that regulation is complex and is modulated on
      several levels. Accordingly, emphasis is here laid on those regulatory feedback
      mechanisms and interdependencies that could help to explain how the pathogenic
      progression from a hypothesized disruptive cause can occur and lead to the
      complex clinical picture in mood disorders. While the 'neurogenic theory' of
      depression remains highly speculative today, it might stimulate the generation of
      sophisticated working hypotheses, useful animal experiments and the first step
      towards new therapeutic approaches.

PMID- 12047493
TI  - Clinical decision-making using the General Behavior Inventory in juvenile
      bipolarity.
AB  - OBJECTIVE: The General Behavior Inventory (GBI) is a questionnaire that has
      utility in the assessment of mood disorders in adults. The purpose of this study
      was to examine how the GBI might optimally be used in the assessment of youths.
      METHOD: Children and adolescents between the ages of 5 and 17 years participated
      in this study. All youths were evaluated with the Schedule for Affective
      Disorders and Schizophrenia for School-Age Children (K-SADS). Based on the K-SADS
      results, subjects were then assigned to one of four groups: a bipolar spectrum
      group, a depressive disorders group, a disruptive behaviors disorders group, and
      a no diagnosis group. Guardians completed a version of the GBI modified for
      parent reporting. Patients 10 years old or greater also completed the GBI as a
      self-report measure. RESULTS: There were 196 subjects who participated. Both
      parent report and youth self-report assigned patients to the appropriate
      diagnostic group with better than 74% accuracy. Combining information from
      multiple informants did not significantly improve diagnostic group assignment.
      CONCLUSIONS: These data suggest that the GBI may be a useful adjunct in the
      diagnosis of mood disorders in youths, particularly when diagnostic specificity
      is more important than sensitivity.

PMID- 12047494
TI  - The impact of response to previous mood stabilizer therapy on response to
      olanzapine versus placebo for acute mania.
AB  - OBJECTIVES: A clinically important question for any new treatment for bipolar
      disorder is whether its efficacy extends to patients who have both responded and
      failed to respond to other mood stabilizers. In this secondary analysis of a
      placebo-controlled trial demonstrating olanzapine's efficacy for acute mania, we
      explore whether its usefulness extends to those patients with a history of poor
      response to other mood stabilizers. METHODS: This 4-week, double-blind, placebo
      controlled trial studied olanzapine monotherapy 5-20 mg/day for hospitalized
      patients in acute manic or mixed bipolar episodes. The primary outcome variable
      was beginning to endpoint change in the Young-Mania Rating Scale (Y-MRS) total
      score. We investigated whether prospectively identified history of recent failure
      to respond to other mood stabilizers predicted response to olanzapine. RESULTS:
      As previously reported, olanzapine-treated patients experienced significantly
      greater improvement in Y-MRS total score and higher remission rates relative to
      placebo-treated patients. The current analysis compared these outcome parameters
      in patients with known poor prior response to lithium and/or valproate with all
      other patients and found no significant group by treatment interactions, i.e.,
      treatment effects were not significantly diminished in non-responders to older
      mood stabilizing agents. CONCLUSIONS: Olanzapine has been shown to be superior to
      placebo for the treatment of mania. This secondary analysis suggests that
      olanzapine monotherapy is similarly effective for patients whether or not they
      previously have failed to respond to another mood stabilizer for mania. A study
      limitation is that response to lithium or valproate was determined
      retrospectively.

PMID- 12047495
TI  - Coping and its correlates among caregivers of patients with bipolar disorder: a
      preliminary study.
AB  - OBJECTIVES: In contrast to schizophrenia, coping patterns of caregivers of
      bipolar patients have not received much attention. Previous evidence suggests
      that demographic factors, illness variables, caregiver burden, appraisal, etc can
      significantly influence coping styles. This study thus attempted to examine
      coping and its correlates in caregivers of bipolar patients, in comparison with
      schizophrenia. METHOD: Structured assessments of dysfunction, burden, appraisal,
      social support available, and coping styles were carried out in caregivers of 38
      bipolar patients and 20 patients with schizophrenia (ICD - 10 diagnoses).
      RESULTS: Caregivers used a wide variety of coping strategies, both problem and
      emotion-focused. In bipolar disorder, demographic parameters, illness duration,
      levels of dysfunction, burden and social support, and appraisal by caregivers
      demonstrated significant associations with coping styles of caregivers. Problem
      focused coping strategies were more common in caregivers of bipolar patients and
      emotion-focused strategies in caregivers of schizophrenic patients. These
      differences appeared to be linked to differences in caregiver-burden and
      appraisal between the two groups. CONCLUSIONS: Appraisal by, and burden on
      caregivers play a major role in determining their style of coping. These factors
      largely accounted for the differences in coping observed between caregivers of
      patients of bipolar disorder and schizophrenia, in this study. Reducing burden on
      caregivers and enhancing their awareness of illness could lead to adoption of
      more adaptive coping styles by them.

PMID- 12047496
TI  - 31P-MRS study of acetyl-L-carnitine treatment in geriatric depression:
      preliminary results.
AB  - OBJECTIVE: This 12-week study of two elderly, depressed subjects investigated the
      effect of acetyl-L-carnitine (ALCAR) treatment on the Hamilton Depression Rating
      Scale (HDRS) and on measures of high-energy phosphate and membrane phospholipid
      metabolism. METHODS: Two mildly depressed (HDRS 15-20), non-demented male
      subjects 70 and 80 years old were compared with six non-demented controls (all
      males, mean age of 73.6 +/- 3.6 years). High-energy and membrane phospholipid
      metabolites were measured by phosphorus magnetic resonance spectroscopic imaging
      (31P MRSI) analysis. HDRS and 31P MRSI measurements were taken at entry, 6 and 12
      weeks for the depressed subjects. RESULTS: 31P MRSI analysis revealed elevated
      levels of phosphomonesters [PME(s - tau(c))] in the prefrontal region of these
      mildly depressed subjects, which decreased with ALCAR treatment and showed a
      trend for correlation of the PME(s - tau(c)) levels with HDRS. ALCAR treatment
      also resulted in increasing levels of the prefrontal phosphocreatine (PCr), which
      correlated with HDRS. CONCLUSIONS: In the prefrontal region, the mildly depressed
      subjects compared with controls had elevated PME(s - tau(c)) levels which
      normalized after 12 weeks of ALCAR and increased PCr levels after ALCAR
      treatment. These preliminary findings suggest further studies are warranted.

PMID- 12047499
TI  - Ketogenic diet in bipolar illness.

PMID- 12047497
TI  - Reduced inositol content in lymphocyte-derived cell lines from bipolar patients.
AB  - OBJECTIVES: The study aimed to determine whether low inositol content and uptake
      previously reported in brain and peripheral tissue of bipolar patients are also
      reflected in lymphocyte-derived cell lines from these patients. METHODS: Inositol
      content and uptake were studied in lymphocyte-derived cell lines grown in vitro
      for at least five generations to eliminate influences of drug treatment. Inositol
      content was studied gas chromatographically and inositol uptake by following 3H
      inositol incorporation at various concentrations. RESULTS: Inositol levels of
      cell lines derived from bipolar patients were significantly lower than those of
      cell lines from controls. CONCLUSIONS: Low inositol content in lymphocyte-derived
      cell lines from bipolar patients corroborates previous findings in frontal cortex
      and in lymphoblastoid cell lines and are consistent with the notion that the
      phosphatidylinositol signaling system is involved in the pathophysiology of this
      disorder.

PMID- 12047498
TI  - Oxcarbazepine treatment of refractory bipolar disorder: a retrospective chart
      review.
AB  - OBJECTIVE: To determine if oxcarbazepine is effective as treatment for refractory
      bipolar illness in a naturalistic setting. METHODS: All charts of out-patients
      treated with oxcarbazepine (n=13) were reviewed and clinical response assessed
      retrospectively using the Clinical Global Impression of Improvement (CGI-I)
      rating scale. All patients had failed treatment with at least one previous mood
      stabilizer. RESULTS: Mild improvement was seen in 46% (n=6) and moderate
      improvement in 16% (n=2). Fifty-four percent (n=7) of the total sample
      discontinued treatment because of adverse effects. CONCLUSION: Oxcarbazepine may
      possess mild to moderate mood-stabilizing properties in this refractory, mostly
      depressed, bipolar sample. This naturalistic study is limited by its uncontrolled
      nature.

PMID- 12047500
TI  - Rural health around the world.

PMID- 12047501
TI  - Short term locum tenens for rural practice: a trial of a Japanese medical school.
AB  - This study investigated locum tenens dispatch to rural practices organised by a
      medical school. Locum tenens has not been studied previously in rural general
      practice, and little has been reported about locum dispatch from an academic
      institution. Since 1990, Jichi Medical School (JMS) has sent faculty members as
      locum tenens to rural practices where its graduates have been working. The
      details of all locum dispatches between 1990 and 1996 were reviewed and analyzed.
      Locum dispatches were performed 486 times for a total of 1233 days from April
      1990 to March 1996. Locum relief was supplied to 15 group practices and 42 solo
      practices which are located throughout most of Japan. Most locum reliefs (98.1%)
      were short and less than one week. There was a wide variety of reasons for
      requesting a locum, ranging from official to personal. The three main reasons
      were practice support (30.5%), continuing medical education (13.8%) and physician
      absence (13.8%). These reasons were different between solo and group practices.
      Solo practices had a more diverse range of inquiries than group practices. In
      group practices, practice support amounted to over half of the inquiry reasons.
      Rural practices face a wide range of circumstances which necessitate locum
      dispatch. Organised locum dispatch by a medical school can provide practical
      support of rural practices through locum tenens dispatch.

PMID- 12047502
TI  - Disease surveillance in rural communities is compromised by address geocoding
      uncertainty: a case study of campylobacteriosis.
AB  - This study illustrates the impact of address geocoding uncertainty on rural
      estimates of reportable disease incidence using campylobacteriosis as an example.
      After all cases of campylobacteriosis notified from 1993 to 1997 had been
      geocoded, the minimum and maximum disease notification rates were calculated for
      rural and urban areas of New Zealand. The estimated maximum rural rates were four
      times higher than estimated minimum rural rates, whereas estimated minimum and
      maximum urban rates varied minimally. The impact of address geocoding on the
      estimation of disease notification rates across Public Health Service Regions
      showed considerable variation. The relative proportions of ungeocoded
      notifications to rural notifications ranged from 1.3:1 to 10.2:1, reflecting the
      range of uncertainty in estimated rural rates of campylobacteriosis. Unless the
      reliability of captured rural address data is improved significantly, disease
      surveillance systems will underestimate rural rates of disease and limit small
      area analyses.

PMID- 12047503
TI  - A comparison of metropolitan and rural medical schools in China: which schools
      provide rural physicians?
AB  - To compare the role of metropolitan and rural medical schools in the provision of
      rural physicians, a survey was conducted in 12 metropolitan and 10 rural medical
      schools. Rural medical schools enrolled fewer students (P = 0.019), and produced
      fewer graduates (P = 0.023) than metropolitan medical schools. Students in rural
      medical schools were mainly from surrounding regional cities and counties,
      whereas those in metropolitan schools were from cities nationwide (P < 0.001).
      All rural medical schools produced rural physicians; one rural school reported
      that of its 256 graduates, 88 (34.4%) entered rural practice. Ten of the 12
      metropolitan medical schools did not produce any rural physicians, whereas the
      remaining two metropolitan schools registered a total of 73 graduates who
      selected a rural practice location. These results indicate that rural medical
      schools may play a key role in overcoming the shortage of physicians in rural
      communities in China.

PMID- 12047504
TI  - Rural health care in Malaysia.
AB  - Malaysia has a population of 21.2 million of which 44% resides in rural areas. A
      major priority of healthcare providers has been the enhancement of health of
      'disadvantaged' rural communities particularly the rural poor, women, infants,
      children and the disabled. The Ministry of Health is the main healthcare provider
      for rural communities with general practitioners playing a complimentary role.
      With an extensive network of rural health clinics, rural residents today have
      access to modern healthcare with adequate referral facilities. Mobile teams, the
      flying doctor service and village health promoters provide healthcare to remote
      areas. The improvement in health status of the rural population using universal
      health status indicators has been remarkable. However, differentials in health
      status continue to exist between urban and rural populations. Malaysia's
      telemedicine project is seen as a means of achieving health for all rural people.

PMID- 12047505
TI  - International perspectives on rural nursing: Australia, Canada, USA.
AB  - This article compares and contrasts nursing practice in rural areas based on
      selected publications by nurse scholars from Australia, Canada and the USA. By no
      means is the analysis complete; rather this preliminary effort is designed to
      provoke interest about rural nursing in the global village. The information can
      be used to examine the rural phenomenon in greater depth from an international
      perspective and challenges nurses to collaborate, study, develop and refine the
      foundations of rural practice across nations and cultures.

PMID- 12047506
TI  - Building the new Northern Ontario Rural Medical School.
AB  - The new Northern Ontario Rural Medical School is to be developed to have a
      significant impact on the education, recruitment, and retention of physicians in
      rural and northern Ontario and Canada. It will be a collaborative partnership
      between Laurentian University, Sudbury and Lakehead University, Thunder Bay (1000
      km apart), and will have a network of learning sites throughout Northern Ontario
      (almost 1,000,000 km2). The curriculum will be patient-centred, clinical problem
      based, and systems-organised, with a significant health determinant focus, and
      Aboriginal health content and context. Small group learning will be used in a
      distributed learning network with advanced information technology support. The
      new Northern Ontario Rural Medical School will aim to graduate highly qualified
      physicians with state-of-the-art medical education, with enhanced knowledge,
      skills, and interest, in Aboriginal, rural, northern, and under serviced health
      care.

PMID- 12047507
TI  - Rural health care in New Zealand: poised for renaissance?
AB  - Despite the idyllic potential, many parts of New Zealand's rural health services
      have continued to struggle for want of a workforce whose retention is not
      threatened by demanding rosters, heavy workloads and overwhelming bureaucracy.
      There may now be a basis for cautious optimism that a plan to integrate
      recommendations and trialled initiatives from the past decade may attract
      sufficient government funding to see a renaissance for rural primary health care.
      This paper outlines the elements contributing to what may be a last hope before
      crisis takes over.

PMID- 12047508
TI  - Project to develop family medicine in rural India.
AB  - The need to develop Family Medicine in the Mayurbhanj region of India is urgent
      and extreme. Among the poorest areas of India, the Mayurbhanj, has an under-5
      mortality twice that of the rest of India. Family physicians in the region are
      severely restricted by the absence of a basic infrastructure for family medicine.
      Supported by a WONCA Foundation Award, this project attempts to address the
      overwhelming healthcare problems of the region and develop a family practice
      network appropriate to the needs of the communities. Working with local Indian
      doctors, specific, achievable goals were set, which included developing a
      maternity protocol and a childhood immunisation program. Community clinics were
      set up in the villages of the project area to enable the scattered remote peoples
      to access medical care. The initiatives of this project are now being continued
      by local Indian family physicians without further outside support.

PMID- 12047509
TI  - Current health scenario in rural India.
AB  - India is the second most populous country of the world and has changing socio
      political-demographic and morbidity patterns that have been drawing global
      attention in recent years. Despite several growth-orientated policies adopted by
      the government, the widening economic, regional and gender disparities are posing
      challenges for the health sector. About 75% of health infrastructure, medical man
      power and other health resources are concentrated in urban areas where 27% of the
      population live. Contagious, infectious and waterborne diseases such as
      diarrhoea, amoebiasis, typhoid, infectious hepatitis, worm infestations, measles,
      malaria, tuberculosis, whooping cough, respiratory infections, pneumonia and
      reproductive tract infections dominate the morbidity pattern, especially in rural
      areas. However, non-communicable diseases such as cancer, blindness, mental
      illness, hypertension, diabetes, HIV/AIDS, accidents and injuries are also on the
      rise. The health status of Indians, is still a cause for grave concern,
      especially that of the rural population. This is reflected in the life expectancy
      (63 years), infant mortality rate (80/1000 live births), maternal mortality rate
      (438/100 000 live births); however, over a period of time some progress has been
      made. To improve the prevailing situation, the problem of rural health is to be
      addressed both at macro (national and state) and micro (district and regional)
      levels. This is to be done in an holistic way, with a genuine effort to bring the
      poorest of the population to the centre of the fiscal policies. A paradigm shift
      from the current 'biomedical model' to a 'sociocultural model', which should
      bridge the gaps and improve quality of rural life, is the current need. A revised
      National Health Policy addressing the prevailing inequalities, and working
      towards promoting a long-term perspective plan, mainly for rural health, is
      imperative.

PMID- 12047511
TI  - Polymorphism of the TT virus and its frequency in Polish blood donors.
AB  - OBJECTIVE: To determine, in Polish blood donors, the frequency of TT virus (TTV)
      using different primers and the sequence diversity of TTV genotypes. MATERIALS
      AND METHODS: Two-hundred blood donors were studied. TTV DNA was detected by the
      polymerase chain reaction (PCR) using primers for the coding (ORF1) and non
      coding (NC) regions. Twenty isolates were genotyped by sequencing the ORF1
      fragment. RESULTS: TTV DNA was detected in 78% of donors using NC primers and in
      10% using ORF1 primers. The frequency of TTV DNA detection by NC primers was
      observed to increase with donor age, whereas the frequency of detection by ORF
      primers did not differ between various age-groups. The nucleotide sequence
      homology of Polish TTV isolates ranged from 59 to 99%. Three genotypes (1b, 2b
      and 2c) were identified. CONCLUSIONS: The frequency of TTV detection depends on
      the primers used for the PCR. Using the NC primers the virus is detected in the
      majority of donors, whereas the ORF1 primers strongly underestimate the
      prevalence of TTV. The frequency of TTV DNA increases with age. Polish TTV
      isolates are highly polymorphic and are classified as 1b, 2b and 2c.

PMID- 12047510
TI  - Automated screening of blood donations for hepatitis C virus RNA using the Qiagen
      BioRobot 9604 and the Roche COBAS HCV Amplicor assay.
AB  - BACKGROUND AND OBJECTIVES: In order to reduce the potential for transmission of
      hepatitis C virus (HCV) from an RNA-positive, anti-HCV-negative blood donation,
      the National Blood Service (NBS) introduced nucleic acid amplification technology
      (NAT) testing for HCV in England and Wales. The objective of this study was to
      develop an automated assay using commercial components for the detection of HCV
      RNA in blood donations for transfusion. MATERIALS AND METHODS: The Qiagen QIAamp
      96 'Viral RNA' and 'Virus' BioRobot kits for HCV RNA extraction, and the Roche
      COBAS HCV Amplicor v2.0 and AmpliScreen v2.0 assays for polymerase chain reaction
      (PCR) amplification and detection, were investigated. RESULTS: QIAamp technology
      and the BioRobot 9604 allow automation of the viral RNA extraction process. By
      combining the automated silica-membrane based QIAamp 96 Virus extraction and
      automated reverse transcription-polymerase chain reaction (RT-PCR) set-up with
      COBAS HCV AmpliScreen v2.0 amplification and detection it is possible to achieve
      a 95% detection level for HCV of 12.8 IU/ml. Cross-contamination studies have
      shown that use of the BioRobot 9604 does not pose a detectable contamination
      risk. Between 1999 and 2001, approximately 6.8 x 106 donations were tested in
      England and Wales, of which only four were found to contain RNA without anti-HCV.
      CONCLUSIONS: This combination of methods results in an assay with a high sample
      throughput, little 'hands-on' time and fast turnaround time that is also
      sufficiently sensitive to allow testing of pools of up to 96 samples at a time.
      These methods have been successfully introduced into routine use within the NBS
      for release of blood components with a shelf-life of longer than 24 h.

PMID- 12047512
TI  - Evidence for de novo synthesis of cytokines and chemokines in platelet
      concentrates.
AB  - BACKGROUND AND OBJECTIVES: Inflammatory cytokines in platelet concentrates (PC)
      may cause side-effects such as febrile non-haemolytic transfusion reactions. The
      maximum white blood cell (WBC) content tolerable to avoid the accumulation of
      cytokines, and whether these cytokines originate from degranulating leucocytes or
      de novo synthesis during storage, had not been investigated prior to this study.
      MATERIAL AND METHODS: We investigated the secretion of interleukin (IL)-1beta, IL
      2, IL-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) and quantified the appropriate expression of corresponding mRNA in PC with
      regard to different levels of WBC contamination and storage times. In addition we
      tested the viability of WBCs during PC storage (by staining with 7
      aminoactinomycin D) and their ability to perform de novo cytokine synthesis (by
      using superantigen stimulation). RESULTS: We detected a statistically significant
      increase of IL-1beta, IL-6, IL-8 and TNF-alpha in PC with > or = 108 WBCs.
      Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed
      increasing mRNA expression of the respective cytokines depending on the number of
      WBC present. On day 5 of storage, WBC viability was > 80% and the leucocytes were
      still able to produce cytokines de novo. CONCLUSIONS: These data show clear
      evidence for de novo synthesis of cytokines in PC. The cytokine pattern supports
      the hypothesis that activated monocytes are responsible for this cytokine
      synthesis. PC with a WBC contamination of > or = 108 contain inflammatory
      mediators in clinically relevant concentrations.

PMID- 12047513
TI  - Influence of prestorage leucocyte depletion and storage time on rheologic
      properties of erythrocyte concentrates.
AB  - BACKGROUND AND OBJECTIVES: Rheological blood properties were studied during
      storage. MATERIALS AND METHODS: Blood viscosity, erythrocyte morphology and ATP
      levels were determined in filtered samples (Leukotrap WB filter system) and their
      unfiltered counterparts during storage with saline-adenine-glucose-mannitol (SAG
      M) for 42 days. RESULTS: Prestorage leucocyte depletion decreased blood viscosity
      at a high shear rate and reduced the degree of anisocytosis of erythrocytes.
      During storage, erythrocytes underwent a time-dependent echinocytic shape
      transformation, which increased the suspension viscosity at high and low shear
      rates. On day 42, high shear viscosity in filtered units remained lower than in
      unfiltered counterparts, the mean cellular volume and red blood cell distribution
      width (RDW) were lower and erythrocytic ATP levels were higher. CONCLUSIONS:
      Prestorage leucocyte depletion by Leukotrap WB filters improves biophysical
      properties of erythrocyte concentrates throughout storage, which is, however,
      outweighed by a time-dependent echinocytic shape transformation and deterioration
      of these properties.

PMID- 12047514
TI  - A novel true volumetric method for the determination of residual leucocytes in
      blood components.
AB  - BACKGROUND AND OBJECTIVES: Accurate determination of residual leucocytes [white
      blood cells (WBC)] in blood components is of high clinical importance. To date,
      several labour-intensive, time-consuming or expensive techniques have been used
      for this purpose. MATERIALS AND METHODS: A method for the determination of
      residual WBC is described using a novel low-cost flow-cytometric cell counter and
      analyser (CCA). The DNA in WBC was stained using 4'-6-diamidino-2-phenylindole
      (DAPI) and WBC were automatically analysed by true volumetric counting of 200
      microl samples (prepared from a 20-microl undiluted sample). RESULTS: Dilution
      experiments over a range of 0.5-50 WBC/microl showed a linearity of r = 0.998.
      The detection limit of this method was 0.83 WBC/microl of red blood cell
      concentrate (RCC) and 0.67 WBC/microl of platelet concentrate (PC), with an
      accuracy of 95.5%. CONCLUSION: Residual WBC (< 1 WBC/microl) can be accurately
      counted using the CCA within 2 min and at a total cost of less than euro 1 per
      sample.

PMID- 12047516
TI  - Further evidence on the high proficiency of laboratories involved in plasma pool
      testing for HCV RNA by nucleic acid amplification technology.

PMID- 12047515
TI  - Acute haemolytic transfusion reactions due to weak antibodies that in vitro did
      not seem to be clinically significant.
AB  - BACKGROUND AND OBJECTIVES: In the present article, we report on two patients with
      acute haemolytic transfusion reactions (AHTRs), and whom we were unable to
      transfuse, owing to alloantibodies that in vitro did not seem to be clinically
      significant. MATERIALS AND METHODS: The patients were a 67-year-old male and a 64
      year-old female, both of whom developed antibodies to red blood cells (RBCs)
      after repeat blood transfusions. Serological analyses were carried out using
      standard techniques. RESULTS: Both patients developed an AHTR of the
      intravascular type following blood transfusions. Serological re-examination
      revealed weakly reactive alloantibodies with anti-JMH specificity in one patient,
      and with unclear specificity in the second. Rechallenging the patients with 15-30
      ml of packed RBCs caused AHTRs, and blood transfusion became impossible in both
      cases. CONCLUSION: Weak alloantibodies that in vitro do not seem to be clinically
      significant may cause severe AHTRs.

PMID- 12047517
TI  - Regarding 'Effectiveness of a protocol to improve transfusion practice in knee
      replacement surgery' by Boralessa et al.

PMID- 12047518
TI  - Massive intravascular haemolysis in a patient with Clostridium perfringens
      sepsis.

PMID- 12047519
TI  - Perioperative triggers for red cell transfusions.

PMID- 12047529
TI  - Pregnancy at high altitude.

PMID- 12047530
TI  - When is seeing believing? The use of color Doppler ultrasound to diagnose
      placenta accreta in the first trimester of pregnancy.

PMID- 12047532
TI  - Lactacidosis in the neonate is minimized by prenatal detection of congenital
      heart disease.
AB  - OBJECTIVES: To investigate the impact of prenatal detection of congenital heart
      disease on preventing severe preoperative lactacidosis. DESIGN: Patients operated
      upon for congenital heart disease during the first 31 days of life (n = 209) were
      studied retrospectively, 21 were diagnosed prenatally and 188 patients had not
      been diagnosed prenatally. Preoperative lactate, pH and base excess were
      evaluated. RESULTS: Differences were noted in preoperative pH (7.28 +/- 0.03 vs.
      7.24 +/- 0.01, P = 0.29), base excess (-5.83 +/- 0.64 vs. -6.93 +/- 0.46 mmol/L,
      P = 0.10) and lactate (3.05 +/- 0.35 vs. 6.08 +/- 0.45 mmol/L, P < 0.001),
      indicating a significant difference in blood lactate values in favor of the
      prenatally diagnosed group. CONCLUSIONS: Prenatal diagnosis of congenital heart
      disease and the resulting immediate postnatal care prevent lactate increase in
      the preoperative period of these patients. This may decrease the risk of cerebral
      damage and result in the patient being in better condition at surgery.

PMID- 12047533
TI  - Normal values of fetal ductus venosus blood flow waveforms during the first stage
      of labor.
AB  - OBJECTIVE: To present normal values of fetal ductus venosus blood flow waveforms
      during the first stage of labor during and between contractions. MATERIALS AND
      METHODS: Seventy-eight women between the 37th and 41st weeks of gestation were
      included in the study. At distinct stages of cervical dilation, blood flow
      velocity waveforms of the fetal ductus venosus during and between contractions
      were visualized in fetuses with a normal non-stress test. The pulsatility index
      for veins, peak velocity index for veins and fetal heart rate were calculated off
      line. The means +/- standard deviations (SD) during and between contractions were
      compared using the Wilcoxon test. RESULTS: Ductus venosus blood flow velocity
      waveforms were visualized during 331 contractions and 375 episodes of uterine
      quiescence in 74 of 78 fetuses (95%) during normal labor. The mean +/- standard
      deviation values of pulsatility and peak velocity indices for veins during
      contractions were 1.66 +/- 0.85 (median: 1.56, range: 0.29-4.69) and 1.46 +/-
      0.65 (median: 1.34, range: 0.26-3.13), respectively. Between contractions the
      values were 0.48 +/- 0.19 (median: 0.46, range: 0.14-1.00) for the pulsatility
      index and 0.44 +/- 0.18 (median: 0.42, range: 0.14-1.00) for the peak velocity
      index for veins. These differences during and between contractions were highly
      significant (P-value < 0.0001), whereas the fetal heart rate showed no
      significant differences. CONCLUSION: There are significant differences in fetal
      ductus venosus blood flow waveforms during and between labor contractions.
      Further studies should evaluate whether these normal values of the fetal ductus
      venosus are beneficial for risk evaluation in fetuses with an abnormal non-stress
      test and/or intrauterine growth restriction.

PMID- 12047531
TI  - Two-dimensional ultrasound is accurate in the diagnosis of fetal craniofacial
      malformation.
AB  - OBJECTIVE: To assess the accuracy of antenatal ultrasound in the diagnosis of
      craniofacial malformations and to compare two-dimensional with three-dimensional
      ultrasound. METHODS: This was a retrospective study in which the archives of our
      ultrasound laboratory were searched for cases with an ultrasound diagnosis of
      craniofacial malformation in the period 1986-2001. No attempt was made to look
      for false-negative diagnoses. RESULTS: Sixty cases with an antenatal diagnosis of
      a craniofacial malformation were found: 37 with cleft lip/palate; 17 with
      heterogeneous dysmorphisms (including mostly micrognathia and craniosynostosis)
      and 6 with miscellaneous craniofacial malformations. Associated anomalies were
      present in 48/60 (80%) cases, and holoprosencephaly (25 cases) was the most
      frequent of these. In 43 (72%) cases the diagnosis was made before 24 weeks'
      gestation. Postnatal follow-up was available for 43 cases and there was always
      complete correlation between antenatal and postnatal diagnoses. Cleft lip/palate
      was always accurately differentiated from cleft lip. Three-dimensional ultrasound
      was performed in 12 cases and was successful in 11. However, it did not provide
      further diagnostic information with regard to the two-dimensional scan.
      DISCUSSION: Current two-dimensional ultrasound in expert hands allows an accurate
      diagnosis of craniofacial abnormalities from early gestation. In our hands, three
      dimensional ultrasound did not add any valuable diagnostic information. Three
      dimensional ultrasound may facilitate the understanding of the lesion by the
      parents and facilitate communication with the plastic surgeons. However, these
      potential benefits need to be carefully weighed against the costs of the
      ultrasound instrumentation, increased examination time and training of personnel.

PMID- 12047534
TI  - Persistent right umbilical vein: incidence and significance.
AB  - OBJECTIVES: To conduct a prospective evaluation of the incidence and neonatal
      outcome of fetuses with persistent right umbilical vein. This condition had
      traditionally been considered to be extremely rare and to be associated with a
      very poor neonatal prognosis, but later evidence has raised some doubts about the
      veracity of these contentions. METHODS: Between August 1995 and November 1998,
      8950 low-risk patients were prospectively evaluated at two medical centers. The
      sonographic diagnosis of a persistent right umbilical vein was made in a
      transverse section of the fetal abdomen when the portal vein was curved toward
      the stomach, and the fetal gall bladder was located medially to the umbilical
      vein. RESULTS: Persistent right umbilical vein was detected in 17 fetuses during
      the study. Four of them had additional malformations, of which three had been
      detected antenatally. CONCLUSIONS: We established that the incidence of
      persistent right umbilical vein in a low-risk population is 1 : 526. We believe
      that the sonographic finding of this anomaly is an indication for conducting
      targeted fetal sonography and echocardiography. When the persistent right
      umbilical vein is connected to the portal system and other anomalies are ruled
      out, the prognosis can generally be expected to be favorable.

PMID- 12047535
TI  - Ultrasonographic evaluation of cervical length in pregnancies complicated by
      preterm premature rupture of membranes.
AB  - OBJECTIVE: To evaluate the usefulness of transvaginal ultrasonography in the
      determination of the risk of preterm delivery and chorioamnionitis in pregnancies
      affected by preterm premature rupture of membranes preterm premature rupture of
      membranes. DESIGN: One hundred and one singleton pregnancies with preterm
      premature rupture of membranes were included in this prospective study over a 3
      year period. Patients underwent cervical length measurement by transvaginal
      ultrasonography at admission and thereafter, in the absence of chorioamnionitis,
      were managed expectantly. RESULTS: The median time interval between admission and
      delivery (latency period) was 48 h. A cervical length of less than 20 mm was
      associated with a significant risk of early delivery (mean latency period was
      59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation
      between cervical length and occurrence of chorioamnionitis or neonatal sepsis.
      CONCLUSIONS: These data suggest that the use of transvaginal ultrasonography for
      cervical length measurement during preterm premature rupture of membranes may
      predict an early delivery but cannot anticipate the risk of chorioamnionitis or
      neonatal sepsis.

PMID- 12047536
TI  - Early fetal anomaly scanning in a population at increased risk of abnormalities.
AB  - OBJECTIVES: To determine the effectiveness of early fetal anomaly scanning in a
      population at risk of fetal anomalies. DESIGN: A prospective study in a tertiary
      center of 101 consecutive fetuses at risk of congenital anomalies at 11-14 weeks
      of gestation. RESULTS: The principal (93/101 = 92%) reason for referral was
      having a previously affected infant. Nine (9/101 = 9%) fetuses were shown to have
      structural anomalies at the 11-14-week scan. In five of nine structurally
      affected fetuses, the nature of the anomalies was similar to that established in
      a previously affected pregnancy, four of which had a recurrence of an autosomal
      recessive syndrome. In two fetuses with a normal 11-14-week scan, anomalies were
      detected at the 18-21-week (arthrogryposis) or 30-week (cardiomyopathy) scans.
      CONCLUSIONS: The majority of fetal anomalies can be diagnosed in the late
      first/early second trimesters of pregnancy. This will be of particular advantage
      to those women who are at high risk of having affected offspring. However, as
      fetal anomalies may present at varying gestational ages, the standard 18-21-week
      scan cannot be abandoned. The effectiveness of the early pregnancy scan depends
      on the natural history of anomalies (gestational age at onset) and the variable
      phenotypic expression of anomalies/syndromes.

PMID- 12047537
TI  - First-trimester, three-dimensional transvaginal ultrasound volumetry in normal
      pregnancies and spontaneous miscarriages.
AB  - OBJECTIVE: The aim of this study was to perform three-dimensional ultrasound
      volumetry of intrauterine contents in cases of normal and failed pregnancies and
      correlate these with conventional two-dimensional measurements. METHODS: This was
      a cross-sectional observational study. Three-dimensional volumetric data were
      collected from a total of 111 patients with first-trimester singleton pregnancies
      together with conventional two-dimensional measurements. A single investigator
      performed all ultrasound scans and volume measurements. RESULTS: Among 111
      participants, 30 had an ongoing pregnancy and 81 had a miscarriage (anembryonic
      pregnancy 30, missed miscarriage 30, and incomplete miscarriage 21). There were
      no significant differences in age, parity, or gestational age between groups. A
      positive linear correlation was demonstrable between the crown-rump length and
      gestational sac volume in normal pregnancies (r = 0.962) and between gestational
      sac volume and gestational age, but the correlation was weaker in cases of missed
      miscarriage (r = 0.561). The volume of the retained products of conception as
      measured by three-dimensional ultrasound volumetry in cases of incomplete
      miscarriage also showed a strong linear correlation (r = 0.938) to their maximum
      anterior-posterior diameter. There was an exponential correlation between the
      mean gestational sac diameter and gestational sac volume and the crown-rump
      length and embryonic volume in cases of both normal and failed pregnancies. The
      mean gestational sac diameter:crown-rump length ratio (P = 0.008) and gestational
      sac volume:embryonic volume ratio (P = 0.023) in missed miscarriages were
      significantly higher than those in ongoing pregnancies. CONCLUSION: Three
      dimensional ultrasound volumetry of intrauterine contents in normal and failed
      pregnancies correlates well with conventional two-dimensional measurements.
      Volumetric assessment does not seem to improve the diagnosis of miscarriage.
      However, its potential to predict pregnancies that will fail and determine the
      appropriate management regime for individual patients merits further research.

PMID- 12047538
TI  - Prenatal age-specific reference intervals for measuring all five digits of the
      fetal hand.
AB  - OBJECTIVE: To construct prenatal age-specific reference intervals for measurement
      of five digits in normal fetuses. PATIENTS AND METHODS: Prospective cross
      sectional study of fetuses assessed at an antenatal ultrasound unit in a
      university-affiliated general hospital. The study cohort comprised 302 pregnant
      women attending our clinic for routine fetal biometry or anomaly scan between
      December 1997 and June 2000. They all fulfilled the study inclusion criteria:
      singleton fetuses with normal anatomy, accurate gestational age and no medical
      complications of pregnancy. Each fetus was scanned once only and the finger
      measurements of one hand were obtained. Electronic calipers were placed on the
      outer margin of the proximal phalanx to the outer margin of the distal phalanx
      level. Those measurements and the relevant gestational age were registered in a
      computerized database. RESULTS: The linear increase of size of each of the five
      fingers was plotted across the evaluated range of gestation (P < 0.001; r2
      between 0.85 and 0.86 for fingers I to V). Tables showing the 5th, 50th and 95th
      centiles of finger lengths between 14 and 27 weeks' gestation were created based
      on the reference interval charts. CONCLUSIONS: Second-trimester measurement of
      all five digits of the fetal hand is feasible. This may assist in the evaluation
      of fetuses that are primarily suspected of having genetic abnormalities that
      might be expressed by deviation in finger length.

PMID- 12047539
TI  - Reference values for fetal limb biometry at 10-14 weeks of gestation.
AB  - OBJECTIVES: To calculate reference ranges for fetal limb measurements obtained by
      transabdominal ultrasound at 10-14 weeks of gestation. METHODS: Six hundred and
      six normal fetuses were examined transabdominally in a cross-sectional study by a
      single observer. The crown-rump length of the fetuses ranged from 31 to 78 mm.
      Measurement of the length of the humerus, ulna, femur, tibia and foot was
      attempted from the longest section of each structure. To assess intraobserver
      repeatability, three sets of repeated measurements were obtained in 26 fetuses.
      RESULTS: An appropriate ultrasound measurement was obtained in a percentage of
      cases ranging from 93.2% to 97.9%. A significant correlation was found between
      crown-rump length measurements and humerus length (r = 0.74, P < 0.001), ulna
      length (r = 0.70, P < 0.001), femur length (r = 0.77, P < 0.001), tibia length (r
      = 0.69, P < 0.001) and foot length (r = 0.58, P < 0.001). Crown-rump length
      specific reference ranges for each measurement were calculated with the method of
      scaled absolute residuals. The study of intraobserver variability showed
      coefficients of variation ranging from 7.9 to 10.0% and intraclass correlation
      coefficients ranging from 0.89 to 0.94. CONCLUSIONS: Fetal limb size is strongly
      correlated with crown-rump length. Despite a significant biological variability
      of the measurements, the availability of reference ranges could be of help in the
      early diagnosis of fetal skeletal dysplasias.

PMID- 12047540
TI  - Determination of gestational age after the 24th week of gestation from fetal
      kidney length measurements.
AB  - OBJECTIVE: To evaluate the application of kidney length measurement to the
      determination of gestational age between the 24th and 38th weeks and to compare
      its accuracy with that of other fetal biometric indices. STUDY DESIGN: Seventy
      three women with singleton uncomplicated pregnancies underwent standard
      ultrasound fetal biometry and kidney length measurement every 2 weeks between 24
      and 38 weeks' gestation. These measurements were used to date the pregnancies
      relative to crown-rump length dating between 8 and 10 weeks' gestation. Linear
      regression models for estimation of gestational age were derived from the
      biometric indices and kidney length. In addition, stepwise regression models were
      constructed to determine the best model for determining gestational age between
      24 and 38 weeks. Comparisons were then made between the accuracy of these models
      in the determination of gestational age. RESULTS: The best model for estimating
      gestational age in late pregnancy included the variables kidney length,
      biparietal diameter, head circumference, femur length and abdominal
      circumference. This model accurately predicted gestational age with a standard
      error of +/- 8.48 days. A model including kidney length, biparietal diameter,
      head circumference and femur length accurately predicted gestational age with a
      standard error of +/- 8.57 days. These models were slightly more accurate than
      models derived from the biometric indices of biparietal diameter, head
      circumference and femur length (+/- 9.87 days), biparietal diameter, head
      circumference, femur length and abdominal circumference (+/- 9.45 days) and
      biparietal diameter and femur length (+/- 9.9 days). Kidney length and femur
      length were the most accurate single parameters for predicting gestational age
      using simple linear regression models (+/- 10.29 and 10.96 days, respectively);
      the abdominal circumference was the least accurate (+/- 14.54 days). CONCLUSION:
      Kidney length is a more accurate method of determining gestational age than the
      fetal biometric indices of biparietal diameter, head circumference, femur length
      and abdominal circumference between 24 and 38 weeks' gestation. When combined
      with biparietal diameter, head circumference and femur length, the precision of
      dating is improved by 2 days. This measurement is easy to make and could
      therefore be easily incorporated into the model for dating pregnancies after 24
      weeks of gestation, in particular when measurements of the biparietal diameter
      and head circumference are difficult.

PMID- 12047541
TI  - Reproducibility of pulsed Doppler measurements of the maternal renal circulation
      in normal pregnancies and those with pregnancy-induced hypertension.
AB  - OBJECTIVE: To assess the inter- and intraobserver reproducibilities of pulsed
      Doppler measurements of the maternal renal circulation in normal pregnancies and
      those affected by pregnancy-induced hypertension. MATERIALS AND METHODS: Color
      and pulsed Doppler ultrasound was used to measure acceleration time and
      resistance index in the renal segmental and interlobar arteries. For the
      investigation of interobserver reproducibility, two sonographers performed
      measurements blindly in six normal pregnant women and 14 women with pregnancy
      induced hypertension between 28 and 36 weeks' gestation. A second group of 10
      patients between 30 and 35 weeks' gestation were examined by one sonographer to
      assess the level of intraobserver reproducibility of measurements. For each
      patient in this group, the flow waveform was measured three times in succession.
      Calculations of the intraclass correlation coefficient Ri were used to determine
      the level of reproducibility. RESULTS: The interobserver Ri and intraobserver Ri
      for acceleration time in the segmental artery were 0.95 and 0.96 and for the
      interlobar artery they were 0.97 and 0.98, respectively. For the resistance
      index, these values were 0.01 and 0.01 in the segmental artery and 0.52 and 0.29
      in the interlobar artery. CONCLUSION: Both the inter- and intraobserver
      reproducibility of acceleration time measurements in the renal segmental and
      interlobar arteries were clinically acceptable but the equivalent
      reproducibilities of resistance index measurements were poor.

PMID- 12047543
TI  - Prenatal diagnosis and perinatal management of left coronary artery to right
      atrium fistula.
AB  - Serious complications due to coronary artery fistulae have been described. Most
      authors recommend early intervention at the time of diagnosis. We present a case
      of a fistula originating from a dilated left coronary artery and draining into
      the right atrium, which was diagnosed prenatally by color Doppler
      echocardiography. During pregnancy, the echocardiographic findings remained
      unchanged, and there were no signs of heart failure. After birth, the fistula was
      confirmed by angiography. Additionally, a persistent left superior vena cava
      draining into the coronary sinus and a very small ventricular septal defect were
      detected. The fistula was closed successfully by transcatheter coil embolization.
      At 17 months old the child was in good clinical condition. Prenatal diagnosis of
      coronary artery fistulae may be possible and may improve perinatal management and
      outcome.

PMID- 12047542
TI  - Recurrent cytomegalovirus infection during pregnancy: ultrasonographic diagnosis
      and fetal outcome.
AB  - Fetal infection as a consequence of recurrent disease is uncommon. We present a
      case of recurrent cytomegalovirus infection in the second trimester of pregnancy.
      Fetal infection was detected through severely abnormal findings on ultrasound
      examination and verified by detecting cytomegalovirus DNA in the amniotic fluid
      and cytomegalovirus-specific immunoglobulin M antibodies in the fetal blood and
      associated pancytopenia. Because of the severity of the infection, a fatal
      outcome was predicted. A Cesarean section was performed at 33+5 weeks of
      gestation; the child died shortly after birth.

PMID- 12047544
TI  - Conservative management of two ectopic pregnancies implanted in previous uterine
      scars.
AB  - Cesarean section scar pregnancy is rare. A variety of interventions have been
      implemented to terminate the pregnancy and preserve the uterus; however, the
      optimal treatment is unknown. We describe two cases of this rare condition
      diagnosed by transvaginal ultrasound. In the first case the diagnosis of an 8
      week non-viable gestation in a uterine scar was made sonographically in a 40-year
      old woman. The patient was treated with intramuscular methotrexate. Myometrial
      integrity was suggested both by ultrasound findings and laparoscopic findings. In
      the second case, an early cervicoisthmic pregnancy in a uterine scar was
      diagnosed by sonography in a 39-year-old woman. This patient was treated
      successfully with a full course of intramuscular methotrexate. Complete
      disappearance of the gestational sac took place 4 months following beta-human
      chorionic gonadotrophin normalization. Intramuscular methotrexate may be a
      treatment alternative for Cesarean section scar pregnancies.

PMID- 12047545
TI  - Placenta accreta diagnosed at 9 weeks' gestation.
AB  - The majority of cases of placenta accreta are unanticipated and initially
      identified intraoperatively. Although color Doppler ultrasound is adequate for
      the evaluation of placenta accreta in the third trimester, ultrasound diagnosis
      in the first trimester has never been reported. To our knowledge, this is the
      first case of placenta accreta detected at 9 weeks' gestation by ultrasound.
      Placenta accreta with intraplacental lacunae can be identified together with a
      loss of the hypoechogenic retroplacental myometrial zone. Based on this case, we
      found that early diagnosis of placenta accreta in the first trimester by
      ultrasound is possible.

PMID- 12047547
TI  - The application of three-dimensional color power Doppler ultrasound in the
      depiction of abnormal uteroplacental angioarchitecture in placenta previa
      percreta.

PMID- 12047546
TI  - Power Doppler evidence of placenta accreta appearing in the first trimester.

PMID- 12047548
TI  - Prenatal diagnosis of fetal face hemangioma in a case of Kasabach-Merritt
      syndrome.

PMID- 12047549
TI  - Sonographic detection of situs inversus, ventricular septal defect, and short-rib
      polydactyly syndrome type III (Verma-Naumoff) in a second-trimester fetus not
      known to be at risk.

PMID- 12047550
TI  - Cesarean delivery scar.

PMID- 12047552
TI  - Clathrin-dependent or not: is it still the question?
AB  - Whether the endocytic uptake of a given molecule is mediated through clathrin
      coated pits or not is a classical criterion used to characterize its endocytic
      pathway(s). Hence, clathrin-dependent endocytosis has been associated with highly
      selective and efficient uptake, whereas clathrin-independent endocytosis appeared
      to be confined to bulk uptake of fluid-phase markers. This scholastic view has
      recently been challenged using newly developed molecular tools that allow for the
      first time a functional and mechanistic analysis of these less well-characterized
      clathrin-independent pathways, including caveolar uptake and macropinocytosis.
      Furthermore, several studies point to a critical role of lateral lipid asymmetry-
      lipid rafts/microdomains--in membrane sorting. We will discuss the potential role
      of these structures in endocytosis and the possibility that differential sorting
      at the plasma membrane predisposes the ensuing intracellular fate of a given
      molecule as well as its physiological function.

PMID- 12047553
TI  - Amphiphysins: raising the BAR for synaptic vesicle recycling and membrane
      dynamics. Bin-Amphiphysin-Rvsp.
AB  - Amphiphysins, members of the BAR (Bin-Amphiphysin-Rvsp) protein super family,
      have been postulated to play a key role in clathrin-mediated endocytosis of
      synaptic vesicles (SVs). This review focuses on recent genetic studies of the
      role of amphiphysins in SV recycling and membrane morphogenesis. In the mouse,
      brain-specific amphiphysin I and II regulate, but are not essential for, SV
      recycling. The role of this regulation appears important, as mice deficient in
      these proteins have seizures and are deficient in learning and memory. In the
      fruit fly Drosophila melanogaster, amphiphysin is found in muscles and is
      enriched at postsynaptic membranes of neuromuscular junctions (NMJs); however, it
      does not play a role in SV recycling. Rather, amphiphysin in fly muscles appears
      to regulate the organization and structure of the muscle T-tubule system and
      possibly the subsynaptic reticulum. Amphiphysin is also involved in membrane
      organization in both neurons and non-neuronal cells in Drosophila. These studies
      reveal pleiotropic functions for amphiphysins in clathrin-mediated endocytosis
      and the regulation of membrane dynamics, perhaps through the actin cytoskeleton.

PMID- 12047554
TI  - Imaging secretory vesicles by fluorescent protein insertion in propeptide rather
      than mature secreted peptide.
AB  - We combined confocal and live-cell imaging with a novel molecular strategy aimed
      at revealing mechanisms underlying glucose-regulated insulin vesicle secretion.
      The 'Ins-C-GFP' reporter monitors secretory peptide targeting, trafficking, and
      exocytosis without directly tagging the mature secreted peptide. We trapped a
      green fluorescent protein (GFP) reporter in equimolar quantity within the
      secretory vesicle by fusing it within the C peptide of proinsulin which only
      after nascent vesicle sealing and acidification is cleaved from the mature
      secreted A and B chains of insulin. Ins-C-GFP expression in mouse islets without
      fail exhibited punctate distribution of green fluorescence by confocal
      microscopy. Ins-C-GFP colocalized GFP with insulin at vesicle dense cores by
      immuno-electron microscopy. Glucose stimulation decreased vesicle fluorescence
      coordinately with enhanced secretion from islets of C-GFP detected by anti-GFP
      Western blots, and of insulin detected by anti-insulin radioimmunoassay. An
      insulin secretagogue with a red fluorescent label, glibenclamide BODIPY TR, was
      applied to islets expressing Ins-C-GFP. The stimulus response was imaged as a
      rise in red secretagogue leading to marked loss in green granules. Since
      neuropeptides as well as peptide hormones are processed from propeptides after
      sealing of secretory granules, vesicle trapping likely is widely applicable for
      studies on targeting, trafficking, and regulated release of secretory peptides.

PMID- 12047555
TI  - Induction of autophagy causes dramatic changes in the subcellular distribution of
      GFP-Rab24.
AB  - Rab GTPases comprises a large family of proteins, with more than 50 gene products
      localized in distinct subcellular compartments. Rab24 is a member of this family
      whose function is not presently known. In order to elucidate the role of this
      protein we have generated a GFP-tagged Rab24 and studied the distribution of this
      chimera by fluorescence microscopy. GFP-Rab24 showed a perinuclear reticular
      localization that often encircled the nucleus. This reticular pattern partially
      overlapped with ER markers, cis-Golgi, and the ER-Golgi intermediate compartment.
      Surprisingly, when GFP-Rab24-transfected cells were starved to induce autophagy
      the distribution of the protein changed dramatically. GFP-Rab24 localized in
      large dots, cup-shaped structures and ring-shaped vesicles. Some of these
      vesicles were labeled with monodansylcadaverine, a specific autophagosome marker.
      In the presence of vinblastine, an agent that induces the formation of very large
      autophagic vesicles, GFP-Rab24 accumulated in the large vacuoles that were also
      labeled by monodansylcadaverine. Furthermore, Rab24 colocalized with LC3, a
      mammalian homolog of the yeast protein Apg8/Aut7, an essential gene for
      autophagy. This is the first report indicating that Rab24 localizes on
      autophagosomes, suggesting that this Rab protein is involved in the autophagic
      pathway.

PMID- 12047556
TI  - GBF1, a guanine nucleotide exchange factor for ADP-ribosylation factors, is
      localized to the cis-Golgi and involved in membrane association of the COPI coat.
AB  - Formation of coated carrier vesicles, such as COPI-coated vesicles from the cis
      Golgi, is triggered by membrane binding of the GTP-bound form of ADP-ribosylation
      factors. This process is blocked by brefeldin A, which is an inhibitor of guanine
      nucleotide exchange factors for ADP-ribosylation factor. GBF1 is one of the
      guanine nucleotide-exchange factors for ADP-ribosylation factor and is localized
      in the Golgi region. In the present study, we have determined the detailed
      subcellular localization of GBF1. Immunofluorescence microscopy of cells treated
      with nocodazole or incubated at 15 degrees C has suggested that GBF1 behaves
      similarly to proteins recycling between the cis-Golgi and the endoplasmic
      reticulum. Immunoelectron microscopy has revealed that GBF1 localizes primarily
      to vesicular and tubular structures apposed to the cis-face of Golgi stacks and
      minor fractions to the Golgi stacks. GBF1 overexpressed in cells causes
      recruitment of class I and class II ADP-ribosylation factors onto Golgi
      membranes. Furthermore, overexpressed GBF1 antagonizes various effects of
      brefeldin A, such as inhibition of membrane recruitment of ADP-ribosylation
      factors and the COPI coat, and redistribution of Golgi-resident and itinerant
      proteins. These observations indicate that GBF1 is involved in the formation of
      COPI-coated vesicles from the cis-Golgi or the pre-Golgi intermediate compartment
      through activating ADP-ribosylation factors.

PMID- 12047557
TI  - SNAP-25 and synaptotagmin 1 function in Ca2+-dependent reversible docking of
      granules to the plasma membrane.
AB  - In neuroendocrine cells, Ca2+ triggers fusion of granules with the plasma
      membrane and functions at earlier steps by increasing the size of the readily
      releasable pool of vesicles. The effect of Ca2+ at early steps of secretion may
      be due to the recruitment at the plasma membrane of granules localized in the
      cytoplasm. To study the mechanism of granule docking, a new in vitro assay is
      designed using membrane fractions from mouse pituitary AtT-20 cells. By using
      this assay, it is found that granule docking to the plasma membrane is controlled
      by Ca2+ concentrations in the micromolar range, is reversible and requires intact
      SNAP-25, but not VAMP-2. In the docking assay, addition of Ca2+ induces the
      formation of a SNAP-25-Synaptotagmin 1 complex. The cytosolic domain C2AB of
      Synaptotagmin 1 and anti-Synaptotagmin 1 antibodies block granule docking. These
      results show that Ca2+ modulates dynamic docking of granules to the plasma
      membrane and that this process is due to a Ca2+-dependent interaction between
      SNAP-25 and Synaptotagmin 1.

PMID- 12047562
TI  - Monitoring sleep hours using a sleep diary and errors in rotating shiftworkers.
AB  - The sleep hours of male workers on rotating shift schedules were measured using a
      sleep diary. The mean age of workers was 40.3 years. Work shifts were rotated on
      a weekly basis and fell into three periods: morning, evening, and night. One
      working week consisted of 5 days. Errors that occurred during the work were also
      evaluated. A significant difference in the mean length of sleep was observed for
      each of the three shifts. Compared with the morning shift, the length of sleep
      for workers working evening and night shifts were significantly longer. The error
      of workers was not recognized in three rotating shift schedules in the survey
      period. Rotating shiftwork affects the amount of sleep, but not the event of
      error.

PMID- 12047563
TI  - Phase shift of coupled oscillator model with feedbacks in response to multiple
      bright light exposure.
AB  - Human temperature rhythm was reported to have type 0 phase response curve (PRC)
      to multiple bright light exposure; however, mechanisms underlying this finding
      could not be clarified easily in a theoretical framework, and has not yet been
      confirmed by other researchers. In this paper, under reproduced photic exposure,
      phase response properties of a coupled three oscillator model were investigated
      to identify the possible mechanism underlying the experimental finding. The
      resulting phase shift of an oscillator reached approximately 12 h, and changed
      its sign acutely at the cross-over point of an original PRC of the oscillator.
      This type 0-like phase shift was produced by an accumulated phase response during
      the oscillator's re-entrainment process to the photic exposure. The organization
      of coupled oscillators affected the total amount of this phase shift.

PMID- 12047564
TI  - Loss of circadian behavioural rhythms in rats kept in constant darkness.
AB  - Ten male Sprague-Dawley rats were exposed to 1-h light and 1-h dark (LD 1 : 1)
      cycles for 50 days. They were then released into constant darkness (DD) for 104
      days. Exposure to LD 1 : 1 caused gradual disruption of circadian rhythms in
      their ambulatory and drinking activities until, finally, all the animals lost
      their circadian behavioural rhythms. After their release into DD, eight rats
      showed free-running circadian behavioural rhythms, whereas the remaining two rats
      showed circadian arrhythmicity for approximately 50 days in DD before they
      restored their free-running rhythms spontaneously.

PMID- 12047565
TI  - Physical symptoms under forced-phase advance treatment in a patient with delayed
      sleep phase syndrome: a case report.
AB  - The physical symptoms that are observed with forced waking in patients with
      delayed sleep phase syndrome (DSPS) often prevent the successful treatment of
      patients. Better understanding of these symptoms will assist in providing
      appropriate treatment in such patients. Herein, a 19-year-old female patient with
      DSPS is described, in whom headache, fatigue, and dizziness were observed under
      forced-phase advance treatment. Statistical analysis showed that her headache was
      dependent on the therapeutic week, and her fatigue was dependent on the period of
      the day. There was no association between dizziness and either factor. Experience
      with this patient indicates that the fatigue observed with forced waking is
      related to the circadian system. This relationship should be explored for other
      physical symptoms as well.

PMID- 12047566
TI  - Alteration of circadian periodicity in core body temperatures of patients with
      acute stroke.
AB  - The effect of brain damage on body temperature rhythm was investigated by
      spectral analysis using the maximum entropy method. The rectal temperatures of 56
      patients with acute stroke were recorded for 1-3 days by actigraphy. Many
      patients with disturbance of consciousness showed infradian rhythm. Ambulatory
      patients tended to have circadian rhythm, and non- ambulatory patients tended to
      show infradian rhythm. The study's findings suggest that impaired physical
      activity and disturbance of consciousness affect body temperature rhythm in
      patients with acute stroke.

PMID- 12047567
TI  - Comparison of sleep/wake habits of university students with or without a habit of
      self-awakening.
AB  - Several studies have reported that some people have the ability to awaken from
      sleep without using external means. This ability is called 'self-awakening'. The
      present study investigated the sleep/wake habits of university students with or
      without a habit of self-awakening. Of the 643 university students, 66 students
      (10.3%) habitually self-awakened in daily life. In comparison with those who did
      not self-awaken (n = 577, 89.7%), self-awakening students went to bed and woke up
      approximately 30 min earlier, felt better when they woke up in the morning, and
      dozed off less in the daytime. Moreover, self-awakening students showed a higher
      morningness score.

PMID- 12047568
TI  - Effect of daytime light conditions on sleep habits and morningness-eveningness
      preference of Japanese students aged 12-15 years.
AB  - The effect of daytime light conditions on the sleep habits and morning-evening
      preference of Japanese junior high school students (415 girls and 411 boys; age
      range, 12-15 years old) was studied. Students who were outdoors during the short
      break between classes or their lunch-time break were more morning-type people
      than those who remained indoors. Students who shut out the light from outside
      showed longer subjective sleep latency and appealed more shallow sleep rather
      than those who did not. Sunlight can be an important factor for the timing of
      sleep based on the circadian system of Japanese young students.

PMID- 12047569
TI  - Morningness-eveningness preference and mood in Japanese junior high school
      students.
AB  - The relationship between morningness-eveningness (M-E) preference and mood in
      Japanese students aged 12-15 years (690 boys and 649 girls) was investigated. No
      significant difference in M-E preference was seen between genders. Girls became
      gloomy more frequently than boys, whereby the girls who experienced melancholy
      more frequently tended to prefer evening. The correlation between mood and M-E
      preference, which was demonstrated only by girls, might be linked to a rapid
      shift to evening preference by girls in the past couple of years.

PMID- 12047570
TI  - Routine evening naps and night-time sleep patterns in junior high and high school
      students.
AB  - This study investigated the relationship between napping and night-time sleep
      patterns in junior high and high school students. A questionnaire concerning
      sleep-related lifestyle was given to about 10,000 junior high and high school
      students. Approximately 50% of the junior high and high school students take at
      least one nap per week. More than 30% of students take naps later than 17.00
      hours. The late naps delayed students' bedtime; that is, onset of night-time
      sleep. The bedtime of students of university-bound high schools was later than
      that of students of vocation-bound high schools. The more frequently students
      took naps, the later they went to bed. Frequent late naps delayed bedtime and,
      hence, shortened the length of night-time sleep.

PMID- 12047571
TI  - Napping predicts responsiveness to hypnotics in patients with primary circadian
      rhythm disorder.
AB  - It is hypothesized that one of the primary abnormalities of primary circadian
      rhythm disorder (PCRD) is the strong link between any episode of sleep and
      circadian rhythm. To test this hypothesis, the relationship between napping and
      responsiveness to hypnotics was examined in 12 patients with PCRD. A significant
      association was found (P = 0.04, chi2 test). Patients with PCRD who napped were
      all responders to hypnotics. The results suggest a strong link between episodes
      of sleep and circadian rhythm in some patients with PCRD, and might also suggest
      the heterogeneity of PCRD. Napping in patients with PCRD may be a predictor for
      responsiveness to hypnotics. In addition, napping and responsiveness to hypnotics
      might have a clinical value to differentiate PCRD from secondary CRD.

PMID- 12047572
TI  - Short naps and exercise improve sleep quality and mental health in the elderly.
AB  - The effects of short naps and exercise on the sleep quality and mental health of
      elderly people was investigated. 'Interventions' by short naps after lunch and
      exercise of moderate intensity in the evening were carried out for 4 weeks. After
      the 'intervention', awake time after sleep onset decreased significantly and
      sleep efficiency increased significantly, demonstrating that sleep quality had
      improved. Also, the frequency of nodding in the evening decreased significantly.
      These results demonstrate that proper awakening maintenance in the evening was
      effective in improving sleep quality. After the 'intervention', mental health and
      volition and physical health had also improved with improving sleep quality.

PMID- 12047573
TI  - An examination of sleep health, lifestyle and mental health in junior high school
      students.
AB  - The factors that influence sleep health and mental health in junior high school
      students' lifestyles was examined. The proportion of students who replied that
      they feel bad in the morning, and who do not have breakfast was significantly
      higher in poor sleepers. The proportion of students who regularly take exercise
      was significantly lower among poor sleepers. Compared with good sleepers, poor
      sleepers had a higher number of illnesses and their General Health Questionnaire
      score was worse. The study's results suggest that sleep health is closely related
      to both physical and mental health, and that habits such as exercise, and regular
      sleeping and eating, are important for maintaining and improving students' sleep
      health.

PMID- 12047574
TI  - A sleep disorders centre in the United Kingdom.
AB  - The demographic features of 296 patients who consulted a sleep disorders centre
      in the United Kingdom were reviewed. Diagnosis after a sleep study was mainly
      that of sleep-related breathing disorders; however, various other sleep disorders
      were also diagnosed. Considering that most sleep disorders are diagnosed only
      after sleep investigations, it should be emphasized that such a facility should
      be well prepared in undertaking not only polysomnography but also various sleep
      investigations, including multiple sleep latency testing and actigraphy. In
      addition, several treatment options, including sleep hygiene, light therapy, and
      behavioural therapy, should be available. Therefore, a sleep disorders centre
      needs to be operated by sleep specialists.

PMID- 12047575
TI  - Prevalence of insomnia in various psychiatric diagnostic categories.
AB  - Sixty percent of 536 new referrals to a psychiatric clinic at a general hospital
      complained of insomnia. Prevalence was high in all psychiatric categories,
      especially in physiologic disorders, somatoform disorders and mood disorders,
      followed by epilepsy. Complaints of difficulty in falling asleep were high in the
      physiologic and somatoform disorder groups. Complaints of nocturnal awakening
      were high in the anxiety and physiologic disorder groups, while complaints of
      early morning awakening were high in the organic and mood disorder groups.
      Prescription rates of hypnotics was most prevalent in the mood and adjustment
      disorder groups, whereas a non-pharmacological approach, including psychological
      education and behavioral therapy, was applied mainly to the physiologic disorder
      group.

PMID- 12047576
TI  - Sleep habits of students attending elementary schools, and junior and senior high
      schools in Akita prefecture.
AB  - It is widely accepted that students in Japan sleep fewer hours than what they
      actually need. However, epidemiological data on sleep habits among students are
      scarce. The sleep habits and related problems among 1650 students in Akita
      prefecture were studied. The results revealed that schoolchildren attending
      elementary schools seemed to sleep for a sufficient number of hours, whereas
      students attending junior or senior high schools were not sleeping enough. In
      particular, approximately half of the students attending senior high schools
      answered that they slept 6 h or less on weekdays and nodded off during classes
      more than twice a week.

PMID- 12047577
TI  - Sleep health and lifestyle of elderly people in Ogimi, a village of longevity.
AB  - The study was conducted in the Prefecture of Longevity, Okinawa, on the elderly
      living in the village of Ogimi. It was revealed that those in the good sleep
      health group took short naps, a significantly fewer number fell into dozes, and a
      significantly greater number exercised regularly or walked. A significantly
      greater number of this group maintained regular eating habits over a 10-year
      span, and consumed more seaweed and fish. Participation in senior citizens' clubs
      was higher, reflecting high emotional adaptability. The study's results indicates
      a relationship between lifestyle and sleep health among the elderly, and suggest
      that deterioration of sleep health is related to physical and mental health.

PMID- 12047578
TI  - Comparative study on sleep health and lifestyle of the elderly in the urban areas
      and suburbs of Okinawa.
AB  - The sleep health and lifestyles of the elderly living in the urban and suburban
      areas of Okinawa prefecture, which is well known for the longevity of its
      inhabitants, were compared. The study revealed that sleep health and activities
      of daily living (ADL) were significantly better among the elderly living in
      suburban areas. There were more complaints of sleep problems from the elderly
      living in urban areas and their bedtimes were significantly later, indicating
      that a nocturnal lifestyle was related to sleep deterioration. In the suburbs, a
      significantly greater number of elderly people regularly took short naps and
      exercised in the evening. The study also suggested that daily habits such as
      short naps and taking appropriate exercise in the evenings contributed to good
      sleep, and that sleep health was related to the ADL of the elderly.

PMID- 12047579
TI  - Analysis of the influence of diurnal variation in maternal movements on fetal
      heart rate acceleration.
AB  - To determine the influence of diurnal variation in maternal movements (MM) on
      fetal heart rate (FHR) accelerations, 24-hour maternal heart rates (MHR), MM and
      FHR recordings were made simultaneously on nine healthy pregnant women at 36-39
      weeks of gestation. Correlations between the diurnal variations in maternal
      factors and FHR parameters; that is, baseline FHR, amplitude, duration and hourly
      percentage of time spent in accelerations, were examined. Only a few cases showed
      a significant correlation between acceleration parameters and the diurnal
      variation of MHR or MM, while most cases indicated a high correlation between the
      diurnal variation in baseline FHR and that of maternal factors. In conclusion,
      the occurrence and form of accelerations might be independent of maternal
      activity.

PMID- 12047580
TI  - Effects of acupuncture to the sacral segment on the bladder activity and
      electroencephalogram.
AB  - Using urethane-anaesthetized rats, the effects of acupunctural stimulation to the
      sacral segment on the urinary bladder activity and cortical electroencephalogram
      (EEG) were examined. The acupuncture suppressed urinary bladder activity in 36 of
      68 trials. On many occasions (22/36 trials), suppression was accompanied by an
      increase in EEG amplitude. In such cases, the EEG power increased in all
      frequency bands after stimulation. The same EEG changes could be induced when the
      bladder was empty with no contraction. The results suggest that acupuncture
      stimulation affects both the bladder activity and sleep-arousal system.

PMID- 12047581
TI  - Longitudinal study for sleep-wake behaviours of mothers from pre-partum to post
      partum using actigraph and sleep logs.
AB  - To understand the sleep-wake behaviours from the fifth pre-partum week to the
      15th post-partum week by the number of actigraphic activities and sleep logs were
      evaluated in 10 women. It was found that total sleep time shortened, sleep
      efficiency decreased, and wake after sleep onset (WASO) increased in the weeks
      immediately after delivery. Compared with late pregnancy, total sleep time and
      sleep efficiency deteriorated significantly from the delivery week to the 12th
      post-partum week and there was a longer period of WASO until the 11th postpartum
      week. The after-delivery sleep parameters estimated by the actigraph were worse
      than those estimated from sleep logs.

PMID- 12047582
TI  - Relationship between amount of sleep and daytime sleepiness in three cases.
AB  - The effect of sleep amount on daytime sleepiness was investigated, and the
      appropriate amount of sleep for each subject was evaluated. Three children were
      longitudinally evaluated for three conditions: control, sleep extension, and
      sleep reduction. A sleep latency test was conducted five times for each condition
      at 2-h intervals from 10.00 hours. The results showed that the effects of sleep
      loss increased sleepiness at 10.00 hours and 18.00 hours, and there were positive
      correlations between sleep amount and sleep latency for each subject (r = 0.590
      0.903). Whether or not the amount of sleep for each subject was sufficient was
      evaluated from the relationship between the two measures.

PMID- 12047583
TI  - Case of head banging that continued to adolescence.
AB  - Head banging is a rhythmic movement disorder (RMD) along with headrolling and
      bodyrolling. The average age of onset is 9 months, and by 10 years of age the
      majority of subjects no longer complain of head banging. A case of head banging
      in which the symptoms continued to adolescence is reported. The RMD involved the
      patient abnormally rolling his body or head and hitting his head on walls during
      sleep. His head bangings were observed during sleep stage 2 and REM sleep. Doses
      of clonazepam ranging from 0.5 mg to 2 mg were administered for the RMD, which
      diminished when treated with 2 mg of clonazepam.

PMID- 12047584
TI  - Comparison of the event-related potentials between tonic and phasic periods of
      rapid eye movement sleep.
AB  - The event-related potentials (ERP) of eight young healthy volunteers were
      recorded during wakefulness and rapid eye movement (REM) sleep using an auditory
      discrimination task. REM sleep was classified into phasic and tonic periods
      according to the presence or absence of REM. In wakefulness, deviant stimuli
      elicited a P300 that was maximal over parieto-central areas. During the tonic
      period of REM sleep, deviant stimuli elicited a P200 and a P400. The P200 was
      distributed more anteriorly and the P400 was distributed more posteriorly than
      the P300; however, no prominent ERP components were observed during the phasic
      period. The study's findings suggest that the brain is less sensitive to external
      stimuli during the phasic period than during the tonic period of REM sleep.

PMID- 12047585
TI  - Brain potentials associated with the onset and offset of rapid eye movement (REM)
      during REM sleep.
AB  - The relationship between dreaming and rapid eye movements (REM) during REM sleep
      is still controversial. This study records the brain potentials time-locked to
      the onset and offset of REM in 11 healthy young volunteers. Before the onset of
      REM, no presaccadic readiness potential was found. Conversely, two positive
      potentials (P1 and P2) appeared following the offset of REM. The latter
      potentials were dominant in the parieto-occipital area. These findings suggest
      that REM is initiated without preparation but elicits some information-processing
      activities that were speculated to occur in the cortical visual area. The data
      support the activation-synthesis or association hypothesis of dreaming rather
      than the scanning hypothesis.

PMID- 12047586
TI  - Nocturnal heart rate and volitional lifestyle in the elderly.
AB  - The relationship between the level of volitional lifestyle and nocturnal heart
      rate (HR) in the elderly was investigated. Twenty high- and low-volitional
      elderly individuals (n = 10 each; mean age 73.2 years) participated in the study.
      Heart rate during nocturnal sleep was recorded at their homes using an ambulatory
      polysomnographic system. High-volitional individuals showed a lower HR throughout
      the night and less variability during rapid eye movement sleep. These findings
      suggest that a volitional lifestyle of the elderly has a beneficial effect on
      autonomic activity during sleep.

PMID- 12047587
TI  - Influence of kappa-rhythm when assessing drowsiness.
AB  - Kappa-rhythm appears at the highest amplitude on a bipolar T3-T4 derivation and
      its frequency range is 7-10 Hz. When a contra-lateral earlobe is used as a
      reference, the kappa-rhythm causes serious problems in assessing drowsiness.
      Assessment of drowsiness using contra- and ipsi-lateral earlobes as references in
      129 subjects who showed kappa-rhythm was compared. Drowsiness could be assessed
      properly in only 26% of subjects using the contra-lateral earlobe and in 90% of
      subjects using the ipsi-lateral earlobe. These results suggest that the ear on
      the ipsi-lateral earlobe should be used as a reference in subjects who show kappa
      rhythm.

PMID- 12047588
TI  - Interhemispheric differences of the correlation dimension in a human sleep
      electroencephalogram.
AB  - The interhemispheric differences of the correlation dimension (D2) in the sleep
      electroencephalogram (EEG) of eight healthy right-handed students was
      investigated. During slow wave sleep (SWS) the D2 of the central EEG and the
      temporal left hemisphere (LH) EEG were significantly higher than those in the
      right hemisphere (RH) EEG; but during rapid eye movement (REM) sleep, the D2 of
      the central EEG and the occipital RH EEG were significantly higher. The D2 of EEG
      in the left temporal site during REM sleep were significantly higher than in the
      right during the first and third sleep cycles, but these were significantly lower
      during the fourth and fifth sleep cycles. During REM sleep, temporal brain
      activity may shift from the LH to the RH as morning approaches.

PMID- 12047590
TI  - Clinical significance of sleep-related breathing disorder in narcolepsy.
AB  - Both the influence of comorbid obstructive sleep apnea-hypopnea syndrome (OSAHS)
      on daytime sleepiness and its pathological mechanism in 10 narcoleptic patients
      was studied. Mild elevation of esophageal negative pressure and obstruction in
      the velopharyngeal area, as observed by upper airway magnetic resonance imaging,
      during apneic episodes was observed in the subjects. Severity of the disorder was
      correlated positively with body mass index, and the latencies of the multiple
      sleep latency tests were not improved with nasal continuous positive airway
      pressure treatment in subjects. Pathogenesis of OSAHS in narcolepsy was thought
      to be almost similar to typical OSAHS, and that the disorder seemed to lack a
      pathological influence on daytime sleepiness.

PMID- 12047589
TI  - Sleep patterns during 30-m nitrox saturation dives and in a confined atmospheric
      environment.
AB  - Sleep patterns during saturation dives equivalent to a 30-m depth (pressurized
      condition) and habitation in a confined environment at 1 atm absolute pressure
      (non-pressurized condition) were studied to determine the effects of
      environmental pressure. Eight inexperienced divers experienced the pressurized
      condition of the saturation dives, and nine healthy subjects experienced the non
      pressurized condition. Standard polysomnographs were recorded for 262 nights. For
      both conditions, reductions in total sleep time accompanied by lengthening in
      sleep latency and reduction in sleep efficiency were observed from the latter
      part of the experiments through to the recovery periods. These findings suggest
      that changes were related to psychological and physiological stresses caused by
      long stays in a confined environment and not by the environmental pressure.

PMID- 12047591
TI  - Methylphenidate hydrochloride for excessive daytime sleepiness in a patient with
      myotonic dystrophy.
AB  - A 28-year-old man with a history of myotonic dystrophy (MyD) is described. His
      progressively worsening excessive daytime sleepiness (EDS) was treated with
      methylphenidate hydrochloride. Polysomonography (PSG), the multiple sleep latency
      test (MSLT), middle latency-evoked response, and auditory event-related
      potentials were used to assess the cause of EDS. The PSG detected small numbers
      of central sleep apneic episodes. Mean sleep latency, which was determined by
      MSLT, increased from 5 min before treatment to 14 min after treatment. The Pa,
      P1, and N1 amplitudes at the Cz site increased after treatment, but P3 latency
      remained unchanged. These observations suggest that EDS and impairment of
      cognitive and information processing seen in a patient with MyD may be caused by
      a central nervous system disorder.

PMID- 12047593
TI  - Analysis of onset location, laterality and propagation of cataplexy in canine
      narcolepsy.
AB  - Hypocretin deficiency is involved in most cases of human narcolepsy. Although
      cataplexy is pathognomonic of narcolepsy, mechanisms of induction of cataplexy
      are largely unknown. Patterns of occurrence of cataplectic attacks (i.e. onset
      location, laterality, and propagation of attacks) in hypocretin receptor 2
      mutated narcoleptic Dobermans were characterized in order to understand the basic
      mechanism of this abnormal sleep-related atonia. Most cataplexy attacks were
      bilateral (98%) and were initiated in the hind legs (80%). Progression of attacks
      was also seen (49%) and atonia during propagation was most often bilateral (94%).
      Involvement of abnormal inactivation of bilateral pathways to the spinal
      motoneurones due to a deficiency in hypocretin neurotransmission is suggested in
      the occurrence of cataplexy.

PMID- 12047592
TI  - Hypocretin-1 (orexin-A) concentrations in cerebrospinal fluid are low in patients
      with Guillain-Barre syndrome.
AB  - It is reported that cerebrospinal fluid (CSF) hypocretin-1 (orexin-A)
      concentrations in patients with narcolepsy are significantly low. Human
      narcolepsy is also known to be closely associated with a specific human
      histocompatibility leukocyte antigen (HLA), suggesting that autoimmunity is
      involved in the pathophysiology of the disease. Thus, it is important to know
      whether hypocretin changes are found in definite neuroimmunological diseases such
      as multiple sclerosis and Guillain-Barre syndrome (GBS). The results of the
      present study indicate that some patients with GBS have lower levels of CSF
      hypocretin-1.

PMID- 12047594
TI  - Decreased blood flow of the left thalamus during somnolent episodes in a case of
      recurrent hypersomnia.
AB  - A 24-year-old male with recurrent hypersomnia associated with decreased blood
      flow in the thalamus on single photon emission computed tomography (SPECT) is
      reported. In the hypersomnolent period, the decrease of blood flow in the left
      thalamus was revealed in the SPECT and slow waves appeared sporadically or
      sometimes as a burst on the electroencephalogram (EEG). In a phase of insomnia in
      the convalescent period there were almost no slow waves in the resting EEG but
      many slow waves appeared on hyperventilation EEG and the power spectrum at this
      hyperventilation resembled the power spectrum at the resting EEG in the
      hypersomnolent period. In the remission period there was no abnormal data in
      these testings.

PMID- 12047595
TI  - Clinical significance of cataplexy and HLADR1501 in narcolepsy.
AB  - Clinical symptoms and multiple sleep latency test (MSLT) measures among
      narcoleptic patients with both cataplexy and HLADR1501 were compared with
      cataplexy-free narcoleptic patients with a positive finding of HLADR1501 and
      cataplexy-free patients without HLADR1501. Both mean sleep onset latencies and
      rapid eye movement (REM) latencies on MSLT were shorter in the patients with
      cataplexy compared with the cataplexy-free patients. In four cataplexy-free
      patients without HLADR1501, nocturnal sleep was remarkably long and their
      excessive daytime sleepiness did not respond to treatment. The findings suggest
      that the severity and disease mechanism of narcolepsy might become heterogenous
      when cataplexy and HLADR1501 are considered.

PMID- 12047596
TI  - Differences in fractal structure of adult heart rate fluctuation between
      successive rapid eye movement sleeps: case report.
AB  - The dynamics of fractal structures of heart rate (HR) fluctuations in successive
      rapid eye movement sleeps (REMS) was investigated in a healthy male. Fractal
      analysis using a purposely-devised method was carried out at 10-min time series
      of HR, which were being recorded simultaneously by an electroencephalogram at
      night. Scaling relationships showed three slopes (alpha(s)). The mean alphas
      below one cross-over point (< 6.0 s), mean alpha(m) between two cross-over
      points, and mean alpha1 above another cross-over point (> 12.0 s) during REMS
      changed from 2.0, 1.0, and 0.3 in the third cycle to 2.0, 0.9, and 1.2 in the
      fourth cycle. The present study demonstrates the differences in multiscaled
      fractal structures of HR fluctuations between the successive REMS in a particular
      case.

PMID- 12047597
TI  - Use of ambulatory skin conductance recording for monitoring psychophysiological
      arousal in the elderly staying in care facilities.
AB  - To monitor the psychophysiological arousal level in the elderly, 24 h recordings
      of skin conductance change (SCC) were done during their stay in care facilities.
      The mean and maximum SCC levels in 17 awake elderly subjects were significantly
      lower than those of levels in 20 healthy, young control subjects (P < 0.05 and P
      < 0.001, respectively). The mean SCC levels during sleep did not differ between
      groups. The SCC trend graph reflected a degree of daily activity. The daytime SCC
      profile of elderly individuals who could walk independently was comparable to
      that of healthy young subjects. In contrast, the SCC profile of the bedridden
      elderly were generally flattened with poor SCC responses that were evoked only by
      nursing procedures.

PMID- 12047598
TI  - Use of an infrared sensor system to take long-term bedside measurements of rest
      activity patterns in the elderly with dementia.
AB  - In order to study long-term rest-activity patterns of elderly residents in care
      facilities, an infrared sensor system was developed. This sensor system detects a
      resident's presence or absence from their bed and their activity with little
      inconvenience. Using this system, the rest-activity patterns of two elderly
      people with dementia was assessed over a period of 3 months. For both subjects,
      frequent activity peaks and absences from their beds were often observed during
      the night. Such a sensor system will be useful for evaluating the sleep-wake
      rhythms of people with sleep disorders.

PMID- 12047599
TI  - Influence of arousal level for functional magnetic resonance imaging (fMRI)
      study: simultaneous recording of fMRI and electroencephalogram.
AB  - Simultaneous recording of functional MRI (fMRI) and electroencephalogram (EEG)
      has been applied to several clinical fields, making it possible to monitor the
      arousal level of the subject during a cognitive task. The study confirmed that
      activated cerebral areas were different between high and low arousal levels
      during the smooth-pursuit eye movement task. When arousal level was high,
      activations in the parietal eye field, frontal eye field (FEF), supplementary eye
      field (SMA), visual fields (V1) and occipito-temporal junction (V5) were found.
      In contrast, when arousal level was low, activations were found only in V1 and
      FEF. The results indicate that the monitoring of the arousal level of subjects
      using fMRI and EEG recordings simultaneously is crucial for detecting cortical
      activations during a cognitive task.

PMID- 12047600
TI  - Study of image findings in rapid eye movement sleep behavioural disorder.
AB  - To elucidate the cause of idiopathic rapid eye movement (REM) sleep behavior
      disorder (RBD), magnetic resonance imaging and single-photon emission computed
      tomography of the brain were conducted on 20 patients with RBD. Blood flow in the
      upper portion of both sides of the frontal lobe and pons was significantly lower
      in patients with RBD than in the normal elderly group. Among the patients with
      RBD, decreased blood flow in the frontal lobe showed no correlation with the
      extent of frontal lobe atrophy. Decreased blood flow in the upper portion of the
      frontal lobe and pons might be associated with the pathogenesis of idiopathic
      RBD.

PMID- 12047601
TI  - Subjective sleep quality and suggested immobilization test in restless leg
      syndrome and periodic limb movement disorder.
AB  - The severity of restless leg syndrome (RLS) and/or periodic limb movement
      disorder (PLMD) was investigated by using a suggested immobilization test (SIT)
      and by measuring the influence of these disorders on the subjective sleep quality
      as assessed by the Pittsburgh Sleep Quality Index (PSQI). Patients with RLS and
      those with both RLS and PLMD showed remarkably high values for PSQI and SIT,
      whereas patients with PLMD only showed normal values for PSQI. These findings
      suggest that there is only a small pathological significance for periodic limb
      movements, and demonstrate the efficacy of SIT and PSQI for evaluating the
      severity of these disorders.

PMID- 12047603
TI  - The study of polysomnography and sleepiness the morning after administration of
      triazolam and brotizolam.
AB  - Using polysomnography, sleep effect was studied, then the sleep latency test
      (SLT), Stanford Sleepiness Scale (SSS), and Kwansei Gakuin Sleepiness Scale (KSS)
      were studied the next morning after administration of either an inactive placebo
      (PL), 0.125 mg triazolam (TL), 0.25 mg triazolam (TH), or 0.25 mg brotizolam
      (BR). Ten healthy male volunteers were used for the double-blind crossover
      design. TL increased the percentage of stage 2 sleep significantly compared with
      PL, whereas TH decreased the number of stage shifts significantly. TH and BR
      increased the percentage of stage 2 sleep significantly and decreased the
      percentage of rapid eye movement sleep significantly. Although no drug had any
      effect on SSS and KSS, BR decreased the sleep latency in SLT significantly.

PMID- 12047602
TI  - Situation and problem of administration methods and the intermission of
      hypnotics.
AB  - The results of a questionnaire survey suggested four problems that might prolong
      the administration of benzodiazepine hypnotics without suspending the medication.
      First, psychiatrists did not actively consider the necessity of suspension of
      medication with hypnotics. Second, the period between improvement of insomnia and
      initiation of dose reduction was long, whereas the period between initiation of
      dose reduction and discontinuation was short. Third, to suspend medication of a
      hypnotic, every-other-day administration was used for the very short-acting and
      short-acting types, and substitution of the intermediate-acting or long-action
      type for the drugs with a short half-life were performed frequently. Finally,
      dose reduction and intermission of medication induced rebound insomnia,
      withdrawal symptoms, and recurrence of insomnia.

PMID- 12047604
TI  - Effects of aroma on sleep and biological rhythms.
AB  - The polysomnogram (PSG), blood melatonin concentration, rectal temperature, and
      answers to a self-evaluation questionnaire about the effects of agarwood (jinkoh
      in Japanese), which has been reported to have sleep-promoting effects were
      examined. The subjects tested were male medical students, who were free of
      otorhinolaryngological diseases and were non-smokers. The results of sleep stage
      and other sleep variables, and those of rectal temperature rhythm and blood
      melatonin concentrations showed no significant differences between the baseline
      nights, experimental nights, and recovery nights.

PMID- 12047605
TI  - Melatonin alleviates jet lag symptoms caused by an 11-hour eastward flight.
AB  - The effect of 3 mg of melatonin on the rate of re-entrainment of plasma melatonin
      rhythm after an 11-h eastward flight was assessed. Eight subjects participated in
      the study, and underwent 24-h blood samplings once before the flight and twice
      after the flight. Subjects were exposed to natural zeitgeber outdoors and took 3
      mg of malatonin at 20:00 h local time on the days when no blood sampling was
      done. Antidromic re-entrainment was dominant whereby melatonin administration in
      the evening promoted re-entrainment. Melatonin accelerated the rate of re
      entrainment by 15 min per day and alleviated the jet lag symptoms.

PMID- 12047606
TI  - Effects of Yoku-kan-san-ka-chimpi-hange on the sleep of normal healthy adult
      subjects.
AB  - Yoku-kan-san-ka-chimpi-hange (YKCH) is a drug used for insomnia in Japanese
      traditional herbal medicine. The present study evaluated the effects of YKCH on
      sleep by all-night polysomnography using the double-blind method. Yoku-kan-san-ka
      chimpi-hange increased the total sleep time significantly, and tended to cause an
      increase in sleep efficiency and of stage 2 sleep, as well as a decrease of sleep
      latency and of stage 3 + 4 sleep. There was no apparent influence on rapid eye
      movement (REM) sleep. In terms of non-REM sleep, the effects of YKCH exhibit a
      profile similar to those of benzodiazepines.

PMID- 12047607
TI  - Hypnotic prescriptions in a university hospital: Analysis of data from the
      computer-ordering system.
AB  - The computer-ordering system (COS) database was used to investigate hypnotic
      prescriptions issued to outpatients at various medical departments at the Dokkyo
      University School of Medicine. Hypnotics were prescribed for 3428 patients (1613
      men, 1815 women), with a mean age of 56 years (range 8-91 years). The number of
      prescriptions was 3.5% of the total number of prescriptions (123 518). Although
      hypnotics were prescribed most often to patients in their 60s, generally, the
      incidence was higher for younger-aged patients. Physicians in all specialty areas
      tended to prescribe short-acting benzodiazepine hypnotics. The issuance of
      hypnotic prescriptions should be investigated to determine the prevalence of
      insomnia in various medical specialties.

PMID- 12047608
TI  - Effects of donepezil (Aricept) on the rapid eye movement sleep of normal
      subjects.
AB  - Donepezil (Aricept) is a therapeutic drug for the treatment of Alzheimer's
      disease (AD). However, there have been only two reports describing the effects of
      donepezil on sleep as assessed by nocturnal polysomnography (PSG). With this in
      mind, the effects of donepezil on the sleep of healthy subjects was evaluated
      using PSG. The results indicated that the percentage of rapid eye movement sleep
      to total sleep time was increased significantly by a single dose of 5 mg of
      donepezil when given to healthy subjects immediately before retiring to bed.

PMID- 12047609
TI  - Hypnotic effects of total aqueous extracts of Vervain hastata (Verbenaceae) in
      rats.
AB  - The in vivo sedative property of the total aqueous extract of the aerial portion
      of Vervain hastata (Verbenaceae) (TAEV) was studied in male rats to establish its
      scientific basis in herbal medicine. The investigation was conducted using
      electroencephalogram (EEG) analysis, and the barbituric-hypnosis test. The
      results showed that TAEV potentiated the pentobarbital-induced hypnosis
      significantly by reducing sleep latency and increased sleeping time in a dose
      dependent manner that was reversed by flumazenil. The EEG data demonstrated that
      extract administration augmented total sleep time, rapid eye movement (REM) sleep
      and non-REM sleep at the expense of wakefulness. The study's results clearly
      showed the scientific validity for the use of this plant as a sedative and
      possibly as a nerve tonic substance.

PMID- 12047610
TI  - Pulmonary hypertension in patients with severe obstructive sleep apnea.
AB  - Thirty-seven patients (35 men and two women) with obstructive sleep apnea
      hypopnea syndrome (OSAHS) without any known cardiovascular and lung diseases were
      examined by Doppler echocardiography. Eight of the 37 (21.6%) patients
      experienced daytime pulmonary hypertension (PH), and all of them had severe OSAHS
      with an apnea-hypopnea index of > 30. The study suggested that one-third of
      patients with severe OSAHS had daytime PH.

PMID- 12047611
TI  - Evaluating mental fatigue in patients with obstructive sleep apnea syndrome by
      the Maastricht Questionnaire.
AB  - Mental fatigue in patients with obstructive sleep apnea syndrome (OSAS) was
      investigated and compared with subjects without OSAS. The study series comprised
      189 habitual snoring patients and 75 controls. To measure subjective mental
      fatigue and somnolence, subjects were asked to complete the Maastricht
      Questionnaire (MQ) and the Epworth Sleepiness Scale (ESS), respectively, and
      patients also underwent diagnostic polysomnography. According to the apnea and
      hypopnea index, patients were classified into the following groups: primary
      snorers, or having mild, moderate, or severe OSAS. The lowest MQ and highest ESS
      scores were found in those patients with severe OSAS. It is proposed that the
      lowest MQ score is due to mental fatigue impairing awareness in patients with
      severe OSAS, probably because of attention loss.

PMID- 12047612
TI  - Using an air-pad sensor for the diagnosis of sleep apnea: a trial study.
AB  - An air-pad sensor (APS) was developed to record respiratory effort non
      invasively. The APS is placed under the subjects' bodies and acoustic signals
      received by the pad are analysed. Nine patients with obstructive sleep apnea
      (OSA) and two healthy subjects were examined using an APS and daytime
      polysomnography, including intraesophageal pressure (Peso), simultaneously. The
      agreement ratio in terms of the central apnea time between the APS and the Peso
      was 93.4%, although the ratio between the Peso and an abdominal strain gauge was
      40.7%. The agreement ratio in terms of respiratory rate among the Peso, APS, and
      abdominal strain gauge in patients with OSA was high; but the agreement ratio was
      low (74.4%) between the Peso and the strain gauge in mixed apnea.

PMID- 12047613
TI  - Endoscopic classification of pharyngeal stenosis pattern in obstructive sleep
      apnea hypopnea syndrome.
AB  - Twenty-one patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) were
      classified into three categories according to their pharyngeal stenosis patterns
      during sleep, as determined from endoscopic findings: (i) a falling type (n = 6);
      (ii) an all-round type (n = 11); and (iii) a bilateral type (n = 4). In all
      patients with the bilateral type, the palatine tonsils were hypertrophied, and
      the apnea-hypopnea indexes (AHI) were improved markedly by surgery. Conversely,
      the AHI of patients with the falling and all-round types were reduced by a
      smaller percentage. Surgical therapy is only to be recommended to patients with
      OSAHS whose pharynx is bilaterally stenotic.

PMID- 12047614
TI  - Diurnal variation in daytime sleepiness of patients with sleep apnea syndrome.
AB  - Diurnal variations in daytime sleepiness were studied in 26 men with sleep apnea
      syndrome (SAS) [age, 41.7 +/- 9.9 years (mean +/- SD); body mass index, 30.0 +/-
      6.2 kg/m2; Epworth Sleepiness Score, 8.7 +/- 4.1; apnea-hypopnea index, 50.2 +/-
      22.0]. Sleep latencies measured at 09.00 h, 11.00 h, 13.00 h, 15.00 h, and 17.00
      h were 3.4 +/- 3.6 min, 4.7 +/- 5.5 min, 5.2 +/- 4.4 min, 5.3 +/- 5.4 min, and
      9.3 +/- 7.2 min, respectively (ANOVA, P < 0.05). Daytime sleepiness in patients
      with SAS was more pronounced in the morning than in the afternoon and evening.

PMID- 12047615
TI  - Rapid eye movement-localized apnea in a female patient with chronic insomnia.
AB  - A middle-aged female patient with chronic insomnia showed rapid eye movement
      (REM)- localized obstructive sleep apnea. She visited the Sleep Disorders Clinic
      and complained of insomnia with loud snoring. Once, in the past, her sleep
      complaints had disappeared after weight reduction but, 6 months later, she
      complained of excessive daytime sleepiness. Overnight polysomnography revealed
      REM-localized apnea. Careful follow up is strongly recommended for a female
      patient with chronic insomnia who shows REM-localized apnea.

PMID- 12047616
TI  - Polysomnographic features of idiopathic central sleep apnea.
AB  - Two patients with idiopathic central sleep apnea (ICSA), which is an uncommon
      condition, were recently encountered. This study examines the polysomnographic
      features of ICSA. The characteristic findings of ICSA are summarized as follows:
      (i) central apneas and hypopneas are progressively less frequent as sleep state
      deepens from stage 1 to stage 2 to stage 3 + 4 to stage REM (rapid eye movement);
      (ii) desaturation related to apneas and hypopneas is mild; and (iii) periodic
      breathing is commonly observed. However, the two patients demonstrated apparently
      different findings. It is suggested that the mechanisms underlying apnea and
      hypopnea in ICSA are heterogeneous.

PMID- 12047617
TI  - A case of sleep choking syndrome improved by the Kampo extract of Hange-koboku
      to.
AB  - A case of sleep choking syndrome with typical symptoms is presented. A 44-year
      old Japanese male suffered from multiple episodes of choking, which suddenly
      appeared with fear of impending death about 30 min after falling asleep almost
      every night. Overnight polysomnography showed an apnea index of 0.92 events/h, an
      apnea-hypopnea index of 2.77 events/h, and normal respiration during sleep with
      the exception of the episodes of apnea and hypopnea. No choking episode occurred
      in the sleep laboratory. The administration of 500 mg of acetazolamide was
      ineffective, but the choking episode improved after the administration of Kampo
      extract of Hange-koboku-to (Ban-xia-hou-pu-tang). Hange-koboku-to may be
      effective in treating choking sensation during sleep as well as during
      wakefulness.

PMID- 12047618
TI  - Facial pattern categories of sleep breathing-disordered children using Ricketts
      analysis.
AB  - The facial patterns of 29 children under the age of 15 years with tonsil and/or
      adenoid and sleep disorder problems was analysed. The lateral-cephalograms of
      these patients was digitized in a zero-based computer program using Ricketts
      analysis to examine facial patterns. Results of the analysis were compared with
      the mean of the control group, n = 41 (9-year-old Japanese children). There were
      significant differences (P < 0.01-0.001) between the patient group and the
      control group when comparing the facial axis, lower facial height, mandibular
      arc, total facial height, and McNamara-Pogonion. The facial pattern of children
      with sleep breathing disorders was discovered to be the dolico facial pattern.

PMID- 12047619
TI  - Effectiveness of a tongue-retaining device.
AB  - The effectiveness of a tongue-retaining device (TRD) was examined at the baseline
      without any TRD [TRD(-)] and then with a TRD [TRD(+)] in eight patients with
      obstructive sleep apnea (OSA). In terms of the 3+ % oxygen desaturation index
      (ODI3), lowest percutaneous oxygen saturation (SpO2), and time spent SpO2 < 90%,
      there were significant differences (P < 0.01-0.05) between the findings for TRD(
      ) and TRD(+). The ODI3 dropped below the baseline by more than 50% in five
      patients (63%) and dropped to fewer than 10 events/ h in six patients (75%). The
      results indicate that oral appliances help patients with mild to moderate OSA;
      however, patients with more severe OSA may also be treated effectively with a
      TRD.

PMID- 12047620
TI  - Falling asleep while driving and automobile accidents among patients with
      obstructive sleep apnea-hypopnea syndrome.
AB  - Among 448 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), 40
      patients (8.9%) had been involved in one or more automobile accidents during the
      preceding 5 years. The main cause of these accidents was falling asleep while
      driving. Excessive sleepiness during driving was associated with an Epworth
      sleepiness scale (ESS) score of > 11 and/or an apnea-hypopnea index (AHI) of >
      15. The automobile accident rate among 182 patients with severe OSAHS (AHI > 30)
      was significantly higher than the rate among 106 simple snorers (AHI < 5).
      Although four of the simple snorers were involved in automobile accidents, their
      ESS scores were all very high (15 or more).

PMID- 12047621
TI  - Effects of orexin on the laterodorsal tegmental neurones.
AB  - Orexin, a hypothalamic neuropeptide, has been revealed to be involved in sleep
      regulation. To elucidate functions of orexin in brainstem sleep regulation
      mechanism, we examined the effects of orexin applied from micropipettes with air
      pressure on neurones in and around the laterodorsal tegmental nucleus (LDT). In
      five of seven cholinergic neurones and six of nine non-cholinergic neurones
      orexin induced long-lasting excitation. These results suggest that hypothalamic
      orexin neurones may affect the LDT neurones directly, and thereby participate in
      control of sleep.

PMID- 12047622
TI  - Involvement of granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      pregnancy-enhanced sleep.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a crucial cytokine
      for establishing pregnancy. It has been demonstrated previously in rats that
      sleep increases during early pregnancy and that centrally administered GM-CSF
      promotes both rapid eye movement (REM) and non-REM sleep. Therefore, whether GM
      CSF is involved in pregnancy-enhanced sleep was investigated using the anti-GM
      CSF antibody. Female rats received an intracerebroventricular infusion of either
      anti-GM-CSF or control IgG (10 microg each) for four nights from the first day of
      pregnancy (PD1-PD4). Although sleep amounts on PD1 were not affected, anti-GM-CSF
      decreased non-REM and REM sleep significantly during PD2-PD4 compared with the
      control baseline of the IgG group. The results demonstrated that anti-GM-CSF
      treatment suppresses pregnancy-enhanced sleep, suggesting that GM-CSF contributes
      to sleep regulation during pregnancy.

PMID- 12047623
TI  - Firing properties of neurones in the laterodorsal hypothalamic area during sleep
      and wakefulness.
AB  - In undrugged, head-restrained rats, neuronal activity was recorded in and around
      the laterodorsal hypothalamic area where orexin neurones are distributed. Among
      22 neurones observed across whole sleep-waking states, half (n = 11) were most
      active during paradoxical sleep and least active during waking. Others were
      equally more active during paradoxical sleep and waking than during slow-wave
      sleep (n = 6), or were most active during waking and least active during
      paradoxical sleep (n = 3). The majority of neurones started to increase firing
      activity prior to the transition of sleep-waking states. These results suggest
      that the area of the hypothalamus containing orexin neurones plays a role in
      sleep-waking regulation.

PMID- 12047624
TI  - Elicited ponto-geniculo-occipital waves by auditory stimuli are synchronized with
      hippocampal theta-waves.
AB  - The study demonstrated that ponto-geniculo-occipital (PGO) waves are phase-locked
      with hippocampal theta-waves during rapid eye movement (REM) sleep. A possible
      mechanism for influencing a PGO wave generator by hippocampal theta-waves was
      hypothesized. The generator is known to receive afferent inputs such as auditory
      input. To test this hypothesis, the temporal relationship between hippocampal
      theta-waves and elicited PGO waves (PGO(E)) by auditory stimuli was analysed. The
      analysis showed that PGO(E) were synchronized with theta-waves, but did not reset
      the phase of a theta-wave. Because the occurrence of PGO(E) and spontaneous PGO
      waves shared the same phase-dependency on theta-waves, the results strongly
      suggest that the PGO wave generator was driven by theta-waves, as originally
      hypothesized.

PMID- 12047625
TI  - Mechanism of cell death and disease resistance induction by transgenic expression
      of bacterio-opsin.
AB  - One of the earliest signal transduction events that trigger the hypersensitive
      response (HR) of plants against pathogen attack is thought to be an alteration of
      proton flux across the plasma membrane (PM). However, no direct genetic evidence
      for the involvement of PM-localised proton channels or pumps in the induction of
      this response has been reported. We previously showed that expression of the
      bacterial proton pump bacterio-opsin (bO) in transgenic plants resulted in the
      spontaneous activation of the HR. Here we show that the bO protein is likely
      localised to the PM in transgenic tobacco plants. Furthermore, mutational
      analysis shows that induction of the HR by bO expression is dependent upon the
      capability of bO to translocate protons. Although bO functions as a light-driven
      proton pump in Halobacteria when assembled with retinal, we also show by
      mutational analysis that this chromophore binding is unnecessary for its in
      planta activity. Taken together, our results suggest that expression of bO in
      plants leads to the insertion of a passive proton channel into the PM. The
      activity of this channel in the PM results in spontaneous activation of cell
      death and HR-associated phenotypes including enhanced resistance to a broad
      spectrum of plant pathogens. Our work provides direct molecular evidence to
      support a working model in which alterations in ionic homeostasis at the level of
      the PM may work as one of the critical steps in the signalling pathway for the
      activation of the HR.

PMID- 12047626
TI  - Expression of Arabidopsis SR-like splicing proteins confers salt tolerance to
      yeast and transgenic plants.
AB  - Searching for novel targets of salt toxicity in eukaryotic cells, we have
      screened an Arabidopsis thaliana cDNA library to isolate genes conferring
      increased tolerance to salt stress when expressed in the yeast Saccharomyces
      cerevisiae. Here we show that expression of the 'alternating arginine-rich' (or
      RS) domains of two different SR-like, putative splicing proteins from Arabidopsis
      allows yeast cells to tolerate higher lithium and sodium concentrations.
      Protection against salt stress appears to require the in vivo phosphorylation of
      these plant polypeptides, since the yeast SR protein kinase Sky1p, which was able
      to phosphorylate in vitro at least one of them, also proved to be essential for
      the observed salt tolerance phenotype. In addition, a clone encoding the U1A
      protein, a previously characterised Arabidopsis splicing factor, was also
      isolated in the screening. No significant decrease in the intracellular
      concentration of lithium was observed in yeast cells incubated in the presence of
      LiCl upon expression of any of the Arabidopsis proteins, suggesting that their
      effects are not mediated by the stimulation of ion transport. In support of the
      general significance of these data, we also show that the expression of the RS
      domain of one of the SR-like proteins in transgenic Arabidopsis plants increases
      their tolerance to LiCl and NaCl. These results point to an important role of pre
      mRNA splicing and SR-like proteins in the salt tolerance of eukaryotic cells,
      offering a novel route to improve this important trait in crop plants.

PMID- 12047627
TI  - Nitric oxide mediates iron-induced ferritin accumulation in Arabidopsis.
AB  - Nitric oxide (NO) is a signaling molecule that plays a critical role in the
      activation of innate immune and inflammatory responses in animals. During the
      last few years, NO has also been detected in several plant species and the
      increasing number of reports on its function in plants have implicated NO as an
      important effector of growth, development and defense. Analogously to animals, NO
      has been recently shown to inhibit tobacco aconitase. This suggests that NO may
      elevate free iron levels in the cells by converting tobacco cytoplasmic aconitase
      into a mRNA binding protein that negatively regulates accumulation of ferritin.
      We investigated the possible role of NO as a regulator of ferritin levels in
      Arabidopsis and found that the NO-donor sodium nitroprusside (SNP) induces
      accumulation of ferritin both at mRNA and protein level. Iron is not necessary
      for this NO-mediated ferritin transcript accumulation, since SNP is still able to
      induce the accumulation of ferritin transcript in Arabidopsis suspension cultures
      pre-treated with the iron chelants DFO or ferrozine. However, NO is required for
      iron-induced ferritin accumulation, as the NO scavenger CPTIO prevents ferritin
      transcript accumulation in Arabidopsis suspension cultures treated with iron. The
      pathway is ser/thr phosphatase-dependent and necessitates protein synthesis;
      furthermore, NO mediates ferritin regulation through the IDRS sequence of the
      Atfer1 promoter responsible for transcriptional repression under low iron supply.
      NO, by acting downstream of iron in the induction of ferritin transcript
      accumulation is therefore a key signaling molecule for regulation of iron
      homeostasis in plants.

PMID- 12047628
TI  - Differential expression and function of Arabidopsis thaliana NHX Na+/H+
      antiporters in the salt stress response.
AB  - The Arabidopsis thaliana vacuolar Na+/H+ antiporter AtNHX1 is a salt tolerance
      determinant. Predicted amino acid sequence similarity, protein topology and the
      presence of functional domains conserved in AtNHX1 and prototypical mammalian NHE
      Na+/H+ exchangers led to the identification of five additional AtNHX genes
      (AtNHX2-6). The AtNHX1 and AtNHX2 mRNAs are the most prevalent transcripts among
      this family of genes in seedling shoots and roots. A lower-abundance AtNHX5 mRNA
      is present in both shoots and roots, whereas AtNHX3 transcript is expressed
      predominantly in roots. AtNHX4 and AtNHX6 mRNAs were detected only by RT-PCR.
      AtNHX1, 2 or 5 suppress, with differential efficacy, the Na+/Li+-sensitive
      phenotype of a yeast mutant that is deficient in the endosomal/vacuolar Na+/H+
      antiporter ScNHX1. Ion accumulation data indicate that these AtNHX proteins
      function to facilitate Na+ ion compartmentalization and maintain intracellular K+
      status. Seedling steady-state mRNA levels of AtNHX1 and AtNHX2 increase similarly
      after treatment with NaCl, an equi-osmolar concentration of sorbitol, or ABA,
      whereas AtNHX5 transcript abundance increases only in response to salt treatment.
      Hyper-osmotic up-regulation of AtNHX1, 2 or 5 expression is not dependent on the
      SOS pathway that controls ion homeostasis. However, steady-state AtNHX1, 2 and 5
      transcript abundance is greater in sos1, sos2 and sos3 plants growing in medium
      that is not supplemented with sorbitol or NaCl, providing evidence that
      transcription of these genes is negatively affected by the SOS pathway in the
      absence of stress. AtNHX1 and AtNHX2 transcripts accumulate in response to ABA
      but not to NaCl in the aba2-1, mutant indicating that the osmotic responsiveness
      of these genes is ABA-dependent. An as yet undefined stress signal pathway that
      is ABA- and SOS-independent apparently controls transcriptional up-regulation of
      AtNHX5 expression by hyper-saline shock. Similar to AtNHX1, AtNHX2 is localized
      to the tonoplast of plant cells. Together, these results implicate AtNHX2 and 5,
      together with AtNHX1, as salt tolerance determinants, and indicate that AtNHX2
      has a major function in vacuolar compartmentalization of Na+.

PMID- 12047630
TI  - Zinc-dependent intermembrane space proteins stimulate import of carrier proteins
      into plant mitochondria.
AB  - Mitochondrial inner membrane carrier proteins are imported into mitochondria from
      yeast, fungi and mammals by specific machinery, some components of which are
      distinct from those utilized by other proteins. Import of two different carriers
      into plant mitochondria showed that one contains a cleavable presequence which
      was processed during import, while the other imported in a valinomycin-sensitive
      manner without processing. Mild osmotic shock of mitochondria released
      intermembrane space (IMS) components and impaired carrier protein import. Adding
      back the released IMS proteins as a concentrate in the presence of micromolar
      ZnCl2 stimulated carrier import into IMS-depleted mitochondria, but did not
      stimulate import of a non-carrier control precursor protein, the alternative
      oxidase. Anion-exchange separation of IMS components before addition to IMS
      depleted mitochondria revealed a correlation between several 9-10 kDa proteins
      and stimulation of carrier import. MS/MS sequencing of these proteins identified
      them as plant homologues of the yeast zinc-finger carrier import components Tim9
      and Tim10. Stimulation of import was dependent on either Zn2+ or Cd2+ and
      inhibited by both N-ethylmalamide (NEM) and a divalent cation chelator,
      consistent with a functional requirement for a zinc finger protein. This
      represents direct functional evidence for a distinct carrier import pathway in
      plant mitochondria, and provides a tool for determining the potential function of
      other IMS proteins associated with protein import.

PMID- 12047629
TI  - Antisense suppression of l-galactose dehydrogenase in Arabidopsis thaliana
      provides evidence for its role in ascorbate synthesis and reveals light modulated
      l-galactose synthesis.
AB  - l-Galactose dehydrogenase (l-GalDH), a novel enzyme that oxidizes l-Gal to l
      galactono-1,4-lactone (l-GalL), has been purified from pea seedlings and cloned
      from Arabidopsis thaliana. l-GalL is a proposed substrate for ascorbate
      biosynthesis in plants, therefore the function of l-GalDH in ascorbate
      biosynthesis was investigated by overexpression in tobacco and antisense
      suppression in A. thaliana. In tobacco the highest expressing lines had a 3.5
      fold increase in extractable activity, but this did not increase leaf ascorbate
      concentration. Arabidopsis thaliana, transformed with an antisense l-GalDH
      construct, produced lines with 30% of wild-type activity. These had lower leaf
      ascorbate concentration when grown under high light conditions. l-Gal pool size
      increased in antisense transformants with low l-GalDH activity, and l-Gal
      concentration was negatively correlated with ascorbate. The results provide
      direct evidence for a role of l-GalDH in ascorbate biosynthesis. Ascorbate pool
      size in A. thaliana is increased by acclimation to high light, but l-GalDH
      expression was not affected. l-Gal accumulation was higher in antisense plants
      acclimated to high light, indicating that the capacity to synthesize l-Gal from
      GDP-mannose is increased. Because the only known function of l-GalL is ascorbate
      synthesis, these antisense plants provide an opportunity to investigate ascorbate
      function with minimal effects on carbohydrate metabolism. Measurements of other
      antioxidants revealed an increase in ascorbate- and pyrogallol-dependent
      peroxidase activity in low-ascorbate lines. As ascorbate is the major hydrogen
      peroxide-scavenging antioxidant in plants, this could indicate a compensatory
      mechanism for controlling hydrogen peroxide concentration.

PMID- 12047631
TI  - Mitochondrial oxidative burst involved in apoptotic response in oats.
AB  - Apoptotic cell response in oats is induced by victorin, a host-selective toxin
      secreted by Cochliobolus victoriae and thought to exert toxicity by inhibiting
      mitochondrial glycine decarboxylase (GDC) in Pc-2/Vb oats. We examined the role
      of mitochondria, especially the organelle-derived production of reactive oxygen
      species (ROS), in the induction of apoptotic cell death. Cytofluorimetric
      analysis showed that victorin caused mitochondrial deltaPsim breakdown and
      mitochondrial oxidative burst. Ultrastructural analysis using a cytochemical
      assay based on the reaction of H2O2 with CeCl3 detected H2O2 eruption at
      permeability transition pore-like sites on the mitochondrial membrane in oat
      cells treated with victorin. ROS generation preceded the apoptotic cell responses
      seen in chromatin condensation and DNA laddering. Both aminoacetonitrile (a
      specific GDC inhibitor) and antimycin A (a mitochondrial complex III inhibitor)
      also induced mitochondrial H2O2 eruption, and led to the apoptotic response in
      oat cells. ROS scavengers such as N-acetyl-l-cysteine and catalase suppressed the
      mitochondrial oxidative burst and delayed chromatin condensation and DNA
      laddering in the victorin- or antimycin A-treated leaves. These findings indicate
      possible involvement of mitochondria, especially mitochondrial-derived ROS
      generation, as an important regulator in controlling apoptotic cell death in
      oats.

PMID- 12047632
TI  - Downregulation of a chloroplast-targeted beta-amylase leads to a starch-excess
      phenotype in leaves.
AB  - A functional screen in Escherichia coli was established to identify potato genes
      coding for proteins involved in transitory starch degradation. One clone isolated
      had a sequence very similar to a recently described chloroplast-targeted beta
      amylase of Arabidopsis. Expression of the gene in E. coli showed that the protein
      product was a functional beta-amylase that could degrade both starch granules and
      solubilized amylopectin, while import experiments demonstrated that the beta
      amylase was imported and processed into pea chloroplasts. To study the function
      of the protein in transitory starch degradation, transgenic potato plants were
      generated where its activity was reduced using antisense techniques. Analysis of
      plants reduced in the presence of this beta-amylase isoform showed that their
      leaves had a starch-excess phenotype, indicating a defect in starch degradation.
      In addition, it was shown that the antisense plants degraded only 8-30% of their
      total starch, in comparison with 50% in the wild type, over the dark period. This
      is the first time that a physiological role for a beta-amylase in plants has been
      demonstrated.

PMID- 12047633
TI  - Improvement of the movement and host range properties of a plant virus vector
      through DNA shuffling.
AB  - Virus expression vectors based on the tobacco mosaic virus (TMV) genome are
      powerful tools for foreign gene expression in plants. However, the inclusion of
      increased genetic load in the form of foreign genes limits the speed of systemic
      plant invasion and host range of these vectors due to reduced replication and
      movement efficiencies. To improve these properties of TMV vectors, the gene
      encoding the 30-kDa movement protein was subjected to mutagenesis and DNA
      shuffling. A vector that expresses the green fluorescent protein was used to
      allow simple visual discrimination of mutants with enhanced movement phenotypes.
      An initial round of mutagenesis produced 53 clones with a faster local movement
      phenotype. Two subsequent rounds of DNA shuffling produced additional clones that
      showed further increased rates of cell-to-cell movement and degrees of systemic
      invasion in restrictive hosts. Surprisingly, sequence analysis of the best
      performing shuffled genes revealed alterations resulting in coding and silent
      changes in the movement protein gene. Separation of these coding and silent
      alterations into distinct gene backgrounds revealed that each contributes to
      improved movement protein function to differing degrees. The resulting vectors
      demonstrate that the complex activities of the movement protein genes of viruses
      can be evolved to have improved movement phenotypes, as evidenced by cell-to-cell
      and systemic invasion. The experiments produced improved vectors that will be of
      use both for in planta functional screening and for therapeutic protein
      production and demonstrated the power of shuffling for plant virus vector
      improvement.

PMID- 12047634
TI  - Use of infrared thermal imaging to isolate Arabidopsis mutants defective in
      stomatal regulation.
AB  - In response to drought, plants synthesise the hormone abscisic acid (ABA), which
      triggers closure of the stomatal pores. This process is vital for plants to
      conserve water by reducing transpirational water loss. Moreover, recent studies
      have demonstrated the advantages of the Arabidopsis stomatal guard cell for
      combining genetic, molecular and biophysical approaches to characterise ABA
      action. However, genetic dissection of stomatal regulation has been limited by
      the difficulty of identifying a reliable phenotype for mutant screening. Leaf
      temperature can be used as an indicator to detect mutants with altered stomatal
      control, since transpiration causes leaf cooling. In this study, we optimised
      experimental conditions under which individual Arabidopsis plants with altered
      stomatal responses to drought can be identified by infrared thermography. These
      conditions were then used to perform a pilot screen for mutants that displayed a
      reduced ability to close their stomata and hence appeared colder than the wild
      type. Some of the mutants recovered were deficient in ABA accumulation, and
      corresponded to alleles of the ABA biosynthesis loci ABA1, ABA2 and ABA3.
      Interestingly, two of these novel aba2 alleles were able to intragenically
      complement the aba2-1 mutation. The remaining mutants showed reduced ABA
      responsiveness in guard cells. In addition to the previously known abi1-1
      mutation, we isolated mutations at two novel loci designated as OST1 (OPEN
      STOMATA 1) and OST2. Remarkably, ost1 and ost2 represent, to our knowledge, the
      first Arabidopsis mutations altering ABA responsiveness in stomata and not in
      seeds.

PMID- 12047637
TI  - Pityriasis rotunda in childhood.
AB  - Pityriasis rotunda is a rare disease characterized by round or oval patches,
      localized mainly on the trunk, arms, and legs. The patches are usually lighter
      than the surrounding skin, but sometimes may be darker, and are covered by fine,
      adherent scales. Two types of pityriasis rotunda have been described. Type I has
      been observed mainly in oriental and black patients older than 60 years of age,
      and is often associated with systemic disease or malignancy. Type II has been
      observed in white patients younger than 40 years of age, is often familial, and
      has never been observed in association with malignancy or internal disease. On
      Sardinia, a cluster of patients with type II pityriasis rotunda has been
      described. From 1981 until 1998, 51 cases of this disease have been observed in
      the Department of Dermatology, University of Sassari; 32 of them were children.
      The great prevalence of pityriasis rotunda on Sardinia, an island which until 40
      years ago had limited contact with the Italian mainland, and the presence of a
      large number of familial cases suggest that type II pityriasis rotunda should be
      considered a genetically determined disease. The trend toward spontaneous
      resolution after the age of 20 years suggests that pityriasis rotunda should be
      considered a genodermatosis with a temporary phenotypic expression.

PMID- 12047636
TI  - What's new in the treatment of viral warts in children.

PMID- 12047638
TI  - Lichen planus in children: a possible complication of hepatitis B vaccines.
AB  - Lichen planus (LP) has been reported as a complication of hepatitis B vaccination
      in both adults and children. According to published observations, an autoimmune
      reaction may be triggered by the viral S epitope. In children, LP is uncommon
      and, because of its atypical clinical presentation, definitive diagnosis may
      require biopsy. We investigated the possible association of recombinant hepatitis
      B virus (HBV) vaccines with childhood LP or LP-like eruptions seen in our
      hospital over the last 3 years. Only biopsy-confirmed cases in which the clinical
      history could be thoroughly scrutinized were included. We report five patients
      less than 16 years of age in whom such an association could be supported by
      relevant data. Thirteen similar pediatric and 15 adult cases have been reported
      from various countries in the last 5 years. The data indicate that LP is a
      complication that rarely occurs in children receiving the HBV vaccine. It appears
      without known predisposing factors and has variable clinical presentations while
      the histologic findings are consistent and, with minor variations, typical of LP.

PMID- 12047639
TI  - Analytical study of pustular eruptions in neonates.
AB  - Pustular eruptions are commonly encountered in neonatal practice. Much confusion
      exists among clinicians because of the similarity in clinical lesions, paucity of
      relevant literature, and varied nomenclature used for these diseases. This often
      results in inappropriate diagnoses and therapies, besides subjecting the neonates
      to invasive and traumatic investigative procedures. We conducted a comprehensive
      study of pustular eruptions in 100 neonates, using the clinical examination and
      simple laboratory tests to arrive at a practical diagnostic and therapeutic
      approach to this problem. Of the 100 neonates with pustular eruptions, 36% were
      in the early neonatal period (first week of life). A slight male preponderance
      with a male:female ratio of 1:0.79 was observed. The majority of the families of
      these infants had poor socioeconomic status (96%) and were living in slums (71%).
      A study of their educational status revealed that 54% of the mothers were
      uneducated. Fifty-seven percent of the neonates were born at home. The clinical
      pattern of diseases among these neonates was that 58% of them had infections
      [impetigo (23%), intertrigo (14%), scabies (6%), and viral diseases (6%)].
      Noninfectious diseases (42%) included miliaria pustulosa, erythema toxicum
      neonatorum, epidermolysis bullosa, and contact dermatitis. Simple laboratory
      investigations helpful in establishing the diagnosis were smears processed with
      Gram (24%) and Giemsa (39%) stains and wet mounts with 10% potassium hydroxide
      (KOH) solution (27%) for direct microscopic examination. More than half (53%) of
      the patients required no specific treatment except for counseling and medications
      to alleviate symptoms, while others with an infectious etiology responded to
      topical and or systemic antibiotics/antifungals. Pustular eruptions in neonates
      include both infectious and noninfectious diseases. Simple laboratory tests such
      as Gram- and Giemsa-stained smears, direct microscopy with 10% KOH wet mounts,
      bacterial and fungal cultures are helpful in establishing the diagnosis and
      occasionally skin biopsy is needed. A practical diagnostic and therapeutic
      approach to this problem is discussed.

PMID- 12047640
TI  - Fixed drug eruption in the genital area in 15 boys.
AB  - Fixed drug eruption (FDE) is manifested as localized, circumscribed, round or
      oval plaques that characteristically recur in the same site with each use of the
      offending drug. The drugs most commonly implicated are phenolphthalein,
      barbiturates, antibiotics, salicylates, contraceptives, and anticonvulsants. FDE
      can appear on different parts of the body. The sites of predilection are the
      lips, genitalia, and sacral area. There are no reports of large series of
      pediatric patients with FDE involving the genitalia. We describe 15 boys with
      genital FDE associated with several drugs. Their average age at diagnosis was
      3.2+/-2.2 years (range 6 months-8 years). The clinical presentation usually
      consisted of swelling and erythema of the penis and/or scrotum associated with
      pruritus, restlessness, urinary retention, and painful micturation. The diagnosis
      was supported by clinical history. The causative drugs were identified and
      confirmed by a provocation test, resolution after the drug was stopped, and a
      positive migration inhibiting factor (MIF) test. Genital FDE in children is
      uncommon, but the drugs associated with this entity are in such widespread use in
      pediatric practice that its recognition may be important, especially considering
      its easy treatability.

PMID- 12047642
TI  - Cutis laxa in seven members of a north-Indian family.
AB  - Congenital cutis laxa, characterized by cutaneous laxity and loose skin, may be
      autosomal dominant or autosomal recessive. The autosomal dominant variety is
      usually not associated with any systemic defects and has a good prognosis. We
      report an unusual family in which seven members were affected by the autosomal
      dominant variant of this disorder. We suggest that close monitoring of the
      cardiorespiratory systems may be worthwhile to detect any systemic complications,
      although these complications are rare in the autosomal dominant variant of cutis
      laxa.

PMID- 12047641
TI  - Recurring staphylococcal scalded skin syndrome-like bullous mastocytosis: the
      utility of cytodiagnosis and the rapid regression with steroids.
AB  - We report a male infant with onset of an extensive bullous eruption at the age of
      45 days. Staphylococcal scalded skin syndrome (SSSS) was suspected. Bullous
      mastocytosis was diagnosed by cytodiagnosis and confirmed by histologic
      examination. Three serious relapses were noted in a 2-year follow-up, and SSSS
      was again suspected because of high fever and leukocytosis with neutrophilia in
      an infectious context. Cytodiagnosis revealed the presence of mast cells and
      permitted rapid diagnosis of recurrences of bullous mastocytosis. Systemic
      corticotherapy dramatically improved the cutaneous lesions and general symptoms.
      This case report emphasizes the utility of cytodiagnosis in extensive blistering
      diseases in infancy and the possibility of obtaining rapid healing by using
      steroids.

PMID- 12047643
TI  - Fatal septicemia in an infant with keratitis, ichthyosis, and deafness (KID)
      syndrome.
AB  - Keratitis, ichthyosis, and deafness (KID) syndrome is a rare congenital disorder
      of unknown etiology in which increased susceptibility to viral, bacterial, and
      mycotic infections has been observed. We report an infant with KID syndrome who
      died from overwhelming systemic infection. To date, investigations into the
      immune function of patients with this syndrome have not revealed a common
      underlying systemic immune deficit. However, the severity of infections and
      multiplicity of organisms observed in this syndrome suggest that a primary
      immunodeficiency is present in addition to an impaired cutaneous barrier to
      microorganisms.

PMID- 12047644
TI  - Neurocutaneous melanosis in association with the Dandy-Walker complex,
      complicated by melanoma: report of a case and literature review.
AB  - Neurocutaneous melanosis is a rare congenital neurocutaneous syndrome in which
      benign and malignant melanocytic tumors of the leptomeninges with large or
      numerous congenital melanocytic nevi develop. The Dandy-Walker malformation
      occurs as a broad posterior fossa with high insertion of the tentorium,
      hypoplasia or aplasia of the cerebellar vermis, and cystic dilation of the fourth
      ventricle communicating with the posterior fossa. Association of these entities
      is very unusual and only 10 previous reports were found in the literature. Our
      patient had multiple, medium-size to small melanocytic nevi present since birth.
      At 5 years of age the patient has intracranial pressure secondary to
      hydrocephalus. A diagnosis of Dandy-Walker malformation and suspected
      neurocutaneous melanosis was established after a skull computed tomography (CT)
      scan. Three months later the patient developed a right frontal tumor shown on the
      CT scan. The histologic finding was nevomelanocytic infiltration with strong
      pleomorphism. The tumor grew rapidly, producing neurogenic shock and death. The
      postmortem report indicated malignant melanoma.

PMID- 12047645
TI  - Eruptive pseudoangiomatosis.
AB  - Eruptive pseudoangiomatosis is a rare, benign, spontaneously regressive disease.
      The term was recently coined to describe a dermatosis characterized by the sudden
      onset of a few to several bright red angioma-like papules with histopathologic
      findings distinct from that of true angiomas. We describe a 7-year-old patient
      with the typical lesions of eruptive pseudoangiomatosis.

PMID- 12047646
TI  - Congenital postauricular swelling in a child.
AB  - First branchial cleft cysts develop as a result of incomplete fusion of the cleft
      between the first and second branchial arches. In 1972, Work introduced a
      modified classification of these anomalies that recognized the existence of two
      types. Type I lesions, which are extremely rare, present as a cystic mass
      posterior to the pinna and concha. Type II lesions represent a duplication of
      both the membranous and cartilaginous portions of the external ear canal. They
      are associated with fistulas in the concha or in the external ear canal. Clinical
      and surgical management is often difficult because these anomalies have a
      variable relationship to the facial nerves. We describe a rare localization of a
      type I first branchial cleft cyst in a child and the clinical management with
      successive surgical treatment.

PMID- 12047647
TI  - Marie Unna hypotrichosis in a Chinese family.
AB  - Marie Unna hypotrichosis is a rare, autosomal dominant hypotrichosis
      characterized by sparse or absent hair at birth with regrowth of coarse, wiry
      hair from childhood, followed by progressive loss on approaching puberty. We
      report a Chinese mother and child seen at our skin center with features of Marie
      Unna hypotrichosis. The family pedigree showed two affected sisters and one
      affected brother, consistent with an autosomal dominant mode of inheritance. The
      clinical, genetic, histologic, and ultrastructural features were consistent with
      the diagnosis of Marie Unna hypotrichosis. This is the first Chinese family
      reported.

PMID- 12047648
TI  - Skin physiology of the neonate and young infant: a prospective study of
      functional skin parameters during early infancy.
AB  - Although neonatal and adult epidermis are similar with respect to thickness and
      lipid composition, skin development is not complete at birth. Previous studies
      indicate that the skin undergoes a process of adaptation and maturation
      postnatally. Postnatal skin physiology has not yet been evaluated comprehensively
      in a prospective study. We assessed skin function parameters prospectively in a
      cohort of 202 healthy term neonates (98 boys) of Caucasian descent. Measurements
      were performed at 3 days, 4 weeks, and 12 weeks of age and at four different body
      sites (frontal area, cheek, volar forearm, and gluteal surface). The following
      parameters were assessed: skin surface pH, corneal layer hydration (capacitance),
      epidermal desquamation, and surface roughness. Data were presented in box and
      whisker plots. Our results were as follows. Surface pH decreased by 0.3-1.1 units
      (p < 0.001), while desquamation increased significantly during the observation
      period (p < 0.001), but only on the facial areas. There was a significant
      increase in stratum corneum hydration (p < 0.001) which was paralleled by
      decreasing skin roughness, indicating smoothing of the skin surface (p < 0.001).
      No significant differences were found between male and female infants. These
      findings reflect significant cutaneous adaptation processes, particularly during
      the neonatal period. Reference values for functional skin parameters may be
      helpful in delineating normal from pathologic skin conditions such as ichthyosis
      or atopic dermatitis at an early stage when intervention might help to prevent
      exacerbations. The usefulness of these reference values will have to be evaluated
      in clinical practice.

PMID- 12047649
TI  - Efficacy of imiquimod 5% cream in the treatment of recalcitrant warts in
      children.
AB  - Long-lasting cutaneous warts are a therapeutic challenge, especially widespread
      or symptomatic recalcitrant warts in children. It can be speculated that natural
      immunity to these human papillomavirus (HPV)- induced lesions is extremely poor.
      Therefore ideally treatment should focus on increasing local immune response.
      Recently imiquimod, a topical immune modifier, has been successfully used in the
      treatment of external genital warts. Our purpose is to report on our experiences
      with imiquimod 5% cream applied to therapy-resistant, long-lasting (duration 2-7
      years) common warts in children. In 18 children, imiquimod cream was self-applied
      by the patients or by their parents to the warts twice a day. Assessment for
      response and occurrence of adverse effects was performed every 4 weeks until
      clinical cure. Follow-ups could be arranged in 14 of the 18 patients 1-2 years
      after total clearance. Sixteen of 18 patients experienced total clearance of
      their warts; 2 showed partial improvement but were lost to follow-up. The mean
      duration of treatment was 5.8 months. Two of the 14 patients in whom a follow-up
      was performed showed a small number of new warts after a period of at least 1
      year without recurrence. Our data demonstrate that the topical application of
      imiquimod 5% cream is an effective treatment for long-lasting cutaneous warts in
      children.

PMID- 12047650
TI  - What syndrome is this? Rabson-Mendenhall syndrome.

PMID- 12047651
TI  - White papules in a child with Down syndrome.

PMID- 12047653
TI  - Early congenital syphilis in the new millennium.

PMID- 12047654
TI  - Subcutaneous granuloma annulare of the scalp in a diabetic child.

PMID- 12047655
TI  - An infant with gigantic subcutaneous calcium deposition following extravasation
      of calcium gluconate.

PMID- 12047659
TI  - Medical education research: is there virtue in eclecticism?

PMID- 12047661
TI  - Back to the future: history and humanism in medical education.

PMID- 12047660
TI  - Towards more empathic medical students: a medical student hospitalization
      experience.

PMID- 12047662
TI  - Reflections on the humanities in medical education.
AB  - BACKGROUND: In recognition of the views advanced by the philosopher Maurice
      Merleau-Ponty, this paper considers some of the implications for medical practice
      and, hence, medical education, of recognizing the human body as an 'intertwining'
      of the natural (or physical) and the existential (or experiential) - something
      which is taken for granted in ordinary experience, but which becomes the medium
      through which disease can manifest itself in illness and disability. Our
      condition is the condition of creatures of frail flesh. Perhaps because this
      'intertwining' is taken for granted, we tend to overlook the extent to which it
      is metaphysically astounding, even though it constitutes the daily arena and
      phenomena of clinical medicine. Clinical medicine is, among other things, the
      routine intervention in this intertwining. This fact is largely discounted by
      biomedical science, which concentrates on 'the natural' at the expense of
      neglecting 'the existential'. Such neglect arguably underlies the perceived
      deficiencies in medical education that the GMC sought to redress in its landmark
      document Tomorrow's Doctors. PROPOSAL: If the humanities disciplines concern
      themselves with recording and interpreting human experiences, the 'medical
      humanities' do so for the human experiences of illness, disability and medical
      intervention. This paper argues for an integrated conception of the medical
      humanities, and for their incorporation into the core medical curriculum. The
      paper concludes by outlining a proposed core module in medical humanities, based
      around a syllabus divided not into the characteristic enquiries of constituent
      disciplines, but rather into groups of topics relating to key philosophical
      questions prompted by the 'intertwining' in embodied human nature.

PMID- 12047663
TI  - Total internal reflection: an essay on paradigms.
AB  - INTRODUCTION: This paper presents a personal view of the relationship between
      science and the humanities within medical education, arguing for a more even
      balance between the two. This view stems from the author's recent experience of
      exploring the literature of learning theory and the social sciences. BACKGROUND:
      For historical reasons, medical education is dominated by a positivistic paradigm
      which assumes the existence of a single objective external reality. This can
      seduce us into believing that positivism is not a paradigm at all, but simply how
      the universe really is. Clinical practice, however, takes place in a much less
      certain world, where reconciling different interpretations of truth is an
      everyday necessity. This paper outlines the perils of uncritical adherence to a
      traditionally 'scientific' mode of thinking. TOTAL INTERNAL REFLECTION: In
      physics, total internal reflection is a phenomenon whereby light is reflected
      from the surface of a liquid without penetrating it, thereby making it impossible
      for anyone within a pool of water to see outside it. The author uses this concept
      as a metaphor to describe a limitation of perspective which characterises
      orthodox medical training, cutting students off from valuable sources of insight
      and understanding. CONCLUSIONS: Medical education often fails to provide learners
      with the tools they need to interpret the literature of other disciplines. In
      particular, it ignores the importance of recognising different perspectives. The
      paper ends by pleading for a more inclusive approach to alternative paradigms
      within our educational system.

PMID- 12047664
TI  - Creativity and medical education.

PMID- 12047665
TI  - Empathy in medical students as related to academic performance, clinical
      competence and gender.
AB  - CONTEXT: Empathy is a major component of a satisfactory doctor-patient
      relationship and the cultivation of empathy is a learning objective proposed by
      the Association of American Medical Colleges (AAMC) for all American medical
      schools. Therefore, it is important to address the measurement of empathy, its
      development and its correlates in medical schools. OBJECTIVES: We designed this
      study to test two hypotheses: firstly, that medical students with higher empathy
      scores would obtain higher ratings of clinical competence in core clinical
      clerkships; and secondly, that women would obtain higher empathy scores than men.
      MATERIALS AND SUBJECTS: A 20-item empathy scale developed by the authors
      (Jefferson Scale of Physician Empathy) was completed by 371 third-year medical
      students (198 men, 173 women). METHODS: Associations between empathy scores and
      ratings of clinical competence in six core clerkships, gender, and performance on
      objective examinations were studied by using t-test, analysis of variance, chi
      square and correlation coefficients. RESULTS: Both research hypotheses were
      confirmed. Empathy scores were associated with ratings of clinical competence and
      gender, but not with performance in objective examinations such as the Medical
      College Admission Test (MCAT), and Steps 1 and 2 of the US Medical Licensing
      Examinations (USMLE). CONCLUSIONS: Empathy scores are associated with ratings of
      clinical competence and gender. The operational measure of empathy used in this
      study provides opportunities to further examine educational and clinical
      correlates of empathy, as well as stability and changes in empathy at different
      stages of undergraduate and graduate medical education.

PMID- 12047666
TI  - Towards more empathic medical students: a medical student hospitalization
      experience.
AB  - OBJECTIVE: We designed a curricular exercise intended to expose healthy medical
      students, near the end of their basic science training, to the experience of
      hospitalization. We attempted to assess how a standardized hospitalization, for
      medical students just about to start their clinical rotations, was experienced by
      student participants. DESIGN: A qualitative observational design was used, both
      to explore the perceptions of the hospitalized students and to generate
      hypotheses for further exploration. SETTING: University and affiliated hospitals.
      PARTICIPANTS: Second-year medical students, towards the end of their basic
      science training. OUTCOME MEASURES: Qualitative assessment of hospitalization
      experience. RESULTS: Among key themes expressed by student participants were the
      following: they felt a profound loss of privacy; they found the nursing staff to
      be caring, attentive and professional, and repeatedly commented about how much
      time the nurses took to talk and listen to them and to take a complete history;
      in contrast they were particularly upset about the distance and coldness they
      felt from the medical staff; they expect this experience to affect their own
      future practice as physicians. When asked how this might change their attitudes
      in the future, students' comments generally reflected a primary concern with
      improving the human aspects of the patient experience. CONCLUSIONS: Student
      participants in a standardized inpatient hospitalization generally experienced
      strong feelings about issues of privacy, and about interactions with medical and
      nursing staff, which they expect to have an important impact on their own
      professional development.

PMID- 12047667
TI  - Comparison between medical students' experience, confidence and competence.
AB  - OBJECTIVES: This study was undertaken to determine whether or not breadth of
      clinical experience and student levels of confidence were indicators of
      competency on standardized simulator performance-based assessments. METHODS: All
      students (n=144) attending an educational session were asked to complete a 25
      point questionnaire regarding specific clinical experiences and levels of
      confidence in their ability to manage patient problems. For enumeration of
      clinical experiences, students were asked to estimate the number of times a
      situation had been encountered or a skill had been performed. For level of
      confidence, each response was based on a 5-point Likert scale where 1=novice and
      5=expert. Students then participated in a standardized simulated performance
      test. Median and range were calculated and data analysed using Spearman rank
      correlations. A P-value <0.05 was considered significant. Level of confidence
      data were compared to performance during clinical rotation and to marks in the
      anaesthesia final examination. RESULTS: A total of 144 students attended the
      session, completed the questionnaire and participated in the standardized test.
      There were wide ranges of experience and confidence in the 25 listed items.
      Analysis of data showed good correlation between clinical experience and level of
      confidence. There was no correlation between clinical experience, level of
      confidence and performance in a standardized simulation test. Neither was there
      any correlation between level of confidence and clinical grades or written
      examination marks. CONCLUSIONS: Clinical experience and level of confidence have
      no predictive value in performance assessments when using standardized
      anaesthesia simulation scenarios.

PMID- 12047668
TI  - The earlier, the better: the effect of early community contact on the attitudes
      of medical students to older people.
AB  - BACKGROUND: Early clinical contact for medical students is an important
      curricular innovation. We wished to determine if early contact with older people
      in the second year of a more vertically integrated medical undergraduate
      programme influenced attitudes to older people and if any effect was synergistic
      with the effect of an existing fourth year course. SUBJECTS: Second and fourth
      year medical students. METHODS: We used a modified version of the Rosencranz
      McNevin semantic differential on ageing to assess attitudes of medical students
      before and after a one-week early community contact week. Some second-year
      students were followed into fourth year and the effect on their attitudes of a
      health care of the elderly course was measured. We compared these data with
      attitude scores from an earlier cohort of students who had undertaken the fourth
      year but not the second-year component. RESULTS: Contact with older people during
      second-year had a significantly favourable effect on attitudes to older people,
      especially for students who saw older people in the community rather than in rest
      homes. The attitudes towards older people of students who had undertaken a fourth
      year clinical health care of the elderly attachment were significantly better on
      two of three subscales than those of fourth-year students who had not seen older
      people during their second year. CONCLUSION: Contact with older people early in a
      medical student's training, and within a more vertically integrated programme,
      has a positive effect on attitudes to older people. This effect may be
      synergistic with contact later in training.

PMID- 12047669
TI  - Stress in doctors and dentists who teach.
AB  - OBJECTIVE: To explore the relationship between a teaching role and stress in
      doctors and dentists who teach. METHODS: Medline, PubMed, BIDS database for
      social sciences literature, and the ERIC database for educational literature were
      searched using the key words 'stress' or 'burnout' with the terms doctor,
      physician, dentist, teacher, lecturer, academic staff, and university staff.
      Other books and journals known to the authors were also used. RESULTS: Many
      studies have shown high levels of stress in doctors, dentists, teachers, and
      lecturers. A large number of factors are implicated, including low autonomy, work
      overload, and lack of congruence between power and responsibility. Doctors and
      dentists who take on a teaching role in addition to their clinical role may
      increase their levels of stress, but there is also evidence that this dual role
      may reduce job-related stress. CONCLUSIONS: Working as a doctor or dentist may
      entail higher levels of stress than are experienced by the general population. In
      some situations adding in the role of teacher reduces this stress, but more
      research is needed to explain this finding.

PMID- 12047670
TI  - Assessing the emotional impact of cadaver dissection on medical students.
AB  - AIM: The study's first aim was to assess the emotional impact of cadaver
      dissection on first year medical students using the newly developed Appraisal of
      Life Events Scale (ALE). Its secondary aim was to evaluate the validity of the
      ALE by comparing it with the Impact of Events Scale (IOE). SETTING: Division of
      Biomedical Sciences, School of Biology, University of St. Andrews. SUBJECTS AND
      METHOD: Appraisal of Life Events and Impact of Events data were obtained from 114
      UK medical students 4 weeks after their first cadaver dissecting class. Main
      outcome measures referred to the ALE and IOE scales. RESULTS: The students rated
      the experience as largely positive, registering significantly higher scores on
      the ALE challenge factor than on ALE threat or ALE loss. Significant correlations
      between ALE threat and loss scores and IOE intrusions and avoidance scores were
      noted. CONCLUSION: The results indicate that medical students do not report their
      first exposure to cadaver dissection as an aversive experience. Instead, as the
      ALE results confirm, they found it to be a positive and challenging life event.
      The ALE appears to be a useful instrument in assessing positive and negative
      emotional reactions to significant life events.

PMID- 12047671
TI  - Serious, frightening and interesting conditions: differences in values and
      attitudes between first-year and final-year medical students.
AB  - CONTEXT AND OBJECTIVE: During medical education and training, the values and
      attitudes of medical students are shaped both by knowledge and by role models. In
      this study, the aim was to compare the views of first- and final-year students
      concerning patients with different medical conditions. PARTICIPANTS AND METHOD:
      In the spring of 1998 all first- and final-year medical students at Goteborg and
      Lund Universities, Sweden, were invited to answer a questionnaire. A total of 20
      medical conditions were to be rated on visual analogue scales, according to three
      aspects: their perceived seriousness, the student's own fear of them and interest
      in working with these conditions in the future. RESULTS: The overall response
      rate was 75%. Concerning seriousness, there was a high degree of concordance
      between the first- and final-year students. Concerning their own fear, the
      concordance was less pronounced. When the conditions were rated from the aspect
      of interest, for the final-year students, gastric or duodenal ulcer replaced
      infection with Ebola virus for the first-year students, among the five highest
      ranked conditions. The correlations between seriousness and fear were lower among
      the final-year students, but this reached statistical significance only in a few
      cases. DISCUSSION: A reasonable interpretation of the results is that the values
      and attitudes of the students were influenced by increased knowledge, as well as
      by role models encountered during the clinical parts of the training. Conditions
      less likely to be contracted become less feared, and conditions with effective
      treatment become more interesting; and the converse was true for each of these
      changes.

PMID- 12047672
TI  - Preparation for palliative care: teaching about death, dying and bereavement in
      UK medical schools 2000-2001.
AB  - AIM: To examine changes in formal teaching about death, dying and bereavement in
      undergraduate medical education in UK medical schools. METHODS: A short
      questionnaire based on one used in 2 previous surveys in 1983 and 1994 was sent
      to all UK medical schools. FINDINGS: All schools with clinical teaching provided
      teaching in this area. The amount of such teaching varied widely and appeared in
      the curriculum in a variety of manners, times and places. Specialists in
      palliative medicine, general practitioners and nurse specialists were most
      frequently involved in teaching, with decreased involvement of non-practitioners
      since 1983. Most schools covered a wide range of topics, with all addressing
      attitudes towards death and dying and symptom relief in advanced terminal
      illness. Some schools used terminally ill patients directly in their teaching and
      most included hospice participation. As the surveys conducted in 1983 and 1994
      indicated, many schools do not address the evaluation of palliative care
      learning. ANALYSIS: Changes in undergraduate medical education, especially in
      terms of more integrated curricula, mean that for many schools, palliative care
      teaching is integrated into learning in other areas. This should help students
      apply their palliative care learning to other contexts. The increase in teaching
      about the management of physical symptoms that has occurred since the previous
      surveys seems to reflect the establishment of palliative medicine as a speciality
      and the current emphases within palliative care practice in the UK. CONCLUSION:
      The preparation for palliative care work provided for current undergraduate
      medical students appears to be of a better quality than that provided in 1983.

PMID- 12047673
TI  - Medical student attitudes toward the doctor-patient relationship.
AB  - CONTEXT: Medical educators have emphasized the importance of teaching patient
      centred care. OBJECTIVES: To describe and quantify the attitudes of medical
      students towards patient-centred care and to examine: (a) the differences in
      these attitudes between students in early and later years of medical school; and
      (b) factors associated with patient-centred attitudes. METHODS: We surveyed 673
      students in the first, third, and fourth years of medical school. Our survey
      utilized the Patient-Practitioner Orientation Scale (PPOS), a validated
      instrument designed to measure individual preferences towards various aspects of
      the doctor-patient relationship. Total PPOS scores can range from patient-centred
      (egalitarian, whole person oriented) to disease- or doctor-centred
      (paternalistic, less attuned to psychosocial issues). Additional demographic data
      including gender, age, ethnicity, undergraduate coursework, family medical
      background and specialty choice were collected from the fourth year class.
      RESULTS: A total of 510 students (76%) completed data collection. Female gender
      (P < 0.001) and earlier year of medical school (P = 0.03) were significantly
      associated with patient-centred attitudes. Among fourth year students (n = 89),
      characteristics associated with more patient-centred attitudes included female
      gender, European-American ethnicity, and primary-care career choice (P < 0.05 for
      each comparison). CONCLUSION: Despite emphasis on the need for curricula that
      foster patient-centred attitudes among medical students, our data suggest that
      students in later years of medical school have attitudes that are more doctor
      centred or paternalistic compared to students in earlier years. Given the
      emphasis placed on patient satisfaction and patient-centred care in the current
      medical environment, our results warrant further research and dialogue to explore
      the dynamics in medical education that may foster or inhibit student attitudes
      toward patient-centred care.

PMID- 12047675
TI  - Facing the challenges of competency-based assessment of postgraduate dental
      training.

PMID- 12047674
TI  - Appraising and assessing reflection in students' writing on a structured
      worksheet.
AB  - BACKGROUND: A variety of teaching and learning techniques intended to engage
      students in reflection are either in use or are being developed in medical and
      dental education. In line with evidence-based practice in education, research is
      needed to appraise the utility and effectiveness of these techniques, so that
      they may be used with confidence. AIM: To assess whether students completing a
      'reflective' learning activity based on a structured worksheet really were
      reflecting. METHOD: A qualitative, multi-method approach was taken. Worksheets
      completed by students were examined for evidence of reflection by researchers
      using two sets of criteria for the assessment of reflection derived from the
      literature, and by peer judges using their own criteria. The opinions of students
      completing the activity, regarding its acceptability and utility, were elicited
      by a questionnaire incorporating a 5-point Likert scale. RESULTS: Results from
      all methods suggest that students completing the activity were reflecting.
      Students' opinions of the activity were mainly positive. CONCLUSION: The methods
      employed may be of use to educators wishing to appraise reflective learning
      activities or, possibly, to assess student reflection.

PMID- 12047676
TI  - Students benefit from experience of hospitalization.

PMID- 12047677
TI  - Sheffield Assessment Instrument for Letters (SAIL).

PMID- 12047679
TI  - Holding on to the philosophy and keeping the faith.

PMID- 12047680
TI  - The assessment tool is only as good as the assessors.

PMID- 12047683
TI  - Training of Doctors project.

PMID- 12047685
TI  - Dehydration in acute gastroenteritis.

PMID- 12047684
TI  - Diagnosis and management of paediatric hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection in children is uncommon and there are few
      guidelines indicating optimal management. It is estimated that 125-250 children
      are infected vertically with HCV in Australia each year and very few of these
      children are diagnosed and followed medically. Without accurate diagnosis and
      follow up, these children cannot be offered optimal care, and are at risk of
      presenting in adult life with significant liver pathology and long-term sequelae.

PMID- 12047686
TI  - Rheumatic fever in Aboriginal children.

PMID- 12047687
TI  - Evaluation of laboratory tests in dehydrated children with acute gastroenteritis.
AB  - OBJECTIVE: The aim of the present study was to demonstrate the utility of
      laboratory tests in predicting dehydration severity. METHODOLOGY: We evaluated
      retrospectively 168 dehydrated children aged 1-21 months with acute
      gastroenteritis. The degree of dehydration in each patient was calculated as the
      percentage change in weight from admission to after rehydration. The associations
      between degree of dehydration, urea, bicarbonate and serum sodium were examined.
      RESULTS: Dehydration severity was significantly related to concentrations of urea
      (P < 0.00001) and bicarbonate (P = 0.01), but not to serum sodium or age.
      Children were divided into three groups on the basis of blood urea: (i) normal (<
      6.7 mmol/L or < 40 mg/dL); (ii) intermediate (6.8-16.6 mmol/L); and (iii) high
      (>or=16.7 mmol/L or >or=100 mg/dL). Groups 1 and 3 had statistically significant
      associations with the degree of dehydration and combining the urea groups with
      plasma bicarbonate levels enhanced the accuracy of predictions. Group 1 had only
      mild to moderate dehydration, but if bicarbonate was 15 mmol/L or higher, there
      was a positive predictive value (PPV) of 93% for mild dehydration. Group 3 had
      moderate to severe dehydration, but if bicarbonate was 15 mmol/L or higher,
      moderate dehydration could be predicted (PPV 100%). Sixty per cent of mildly
      dehydrated children (32/53) had low bicarbonate, but only 7% (2/29) with
      bicarbonate 15 mmol/L or higher had severe dehydration. Serum sodium did not have
      any significant association with the degree of dehydration, or the levels of
      bicarbonate or urea. CONCLUSIONS: The results suggest that serum urea and
      bicarbonate concentrations can be helpful in the estimation of fluid deficit
      independently from serum sodium concentration, and may be considered to be
      adjuncts to clinical evaluation in assessing the degree of dehydration.

PMID- 12047688
TI  - Systematic review of rheumatic heart disease prevalence in children in developing
      countries: the role of environmental factors.
AB  - OBJECTIVES: To consider the worldwide prevalence of rheumatic heart disease in
      children in developing countries using surveys with uniform methodologies, and to
      consider the effect of environmental factors including socio-economic status,
      overcrowding, urbanization, nutrition and access to medical services on the
      distribution of rheumatic heart disease in developing countries. METHODS: Sixty
      one surveys of the prevalence of rheumatic heart disease in developing countries
      were found using a systematic review of MEDLINE from January 1976 to July 1999.
      Twenty-four studies were selected for comparison based on their uniform
      methodological and diagnostic techniques. RESULTS: There is a high prevalence of
      rheumatic heart disease in the Pacific region with a lower prevalence in the
      Indian subcontinent, Asian, sub-Saharan African, Mediterranean, Latin American
      and Caribbean regions. However, aside from the Indian subcontinent, these regions
      have not been well studied, and it may be that the true prevalence is actually
      higher. CONCLUSIONS: There is a lack of good quality prevalence surveys of
      rheumatic heart disease in developing countries. It appears that a threshold
      level where higher socio-economic status is associated with reduced prevalence of
      rheumatic heart disease is not reached in developing countries. Therefore,
      differences in prevalence between socio-economic groups in the one area cannot be
      detected. A similar case can be made for overcrowding. Many regions need well
      designed studies of rheumatic heart disease that incorporate assessment of
      environmental factors as well as the study of the microbiological epidemiology of
      rheumatic heart disease and group A streptococci.

PMID- 12047689
TI  - Variation in mortality and intraventricular haemorrhage in occupants of Pacific
      Rim nurseries.
AB  - OBJECTIVE: A network of neonatal intensive care units in Pacific Rim countries
      was formed to compare infant risk factors, clinical practices, and outcomes for
      very low birthweight infants. METHODOLOGY: A multicentre, prospective study
      compared outcomes for infants born smaller than 1501 g or at less than 31 weeks
      gestation. RESULTS: Gestational age-specific survival and incidence of
      intracranial haemorrhage varied for infants born in these nurseries. We found
      differences in infant risk factors among the nurseries. There were also
      significant differences in the use of antenatal steroids, but similar rates for
      Caesarean section and surfactant treatment. The factor most predictive of
      neonatal death and severe intracranial abnormality was an elevated Clinical Risk
      Index for Babies (CRIB) score. Antenatal steroid treatment (>24 h prior to
      delivery) was associated with improved survival and decreased incidence of severe
      intracranial abnormalities. Antenatal steroid treatment for less than 24 h prior
      to delivery was not associated with improved survival. Caesarean delivery was
      associated with improved survival, but showed no benefit regarding the incidence
      of severe intracranial abnormality. CONCLUSIONS: Our Pacific Rim nursery network
      found differences in neonatal outcomes that correlated best with measures of
      neonatal risk at birth, antenatal steroid treatment, and Caesarean delivery.
      These data emphasize the importance of obstetric care to improve postnatal
      outcomes in premature infants, and highlight the usefulness of CRIB scores in
      these patients.

PMID- 12047690
TI  - Improvement in resuscitation knowledge after a one-day paediatric life-support
      course.
AB  - OBJECTIVE: To assess the effect of a one-day paediatric life-support course on
      the knowledge of paediatric trainees. METHODS: A telephone survey was performed
      prior to and at set intervals following the course. Responses to individual
      questions before and after the course were analysed and an overall test score was
      calculated. The acquisition and retention of knowledge was measured by comparing
      test scores for the same group of trainees at time intervals after the course.
      RESULTS: All candidates were surveyed. The median duration of paediatric training
      prior to the course was 3 years. Eighteen candidates (78%) had previously
      intubated a child and 13 (57%) had previously used an intraosseous needle. Prior
      to the course, few of the 23 candidates had adequate knowledge of either the
      management of the cervical spine in the seriously injured child (17%), fluid
      resuscitation in meningococcal septicemia (52%), shock dose in ventricular
      fibrillation (61%), or the management of anaphylactic shock (35%). There was a
      significant improvement in the knowledge of the group after the course, with
      median test scores increasing from 19 to a maximum of 22 (P < 0.001). This
      knowledge was retained at 4 months after the course. CONCLUSION: Despite a high
      level of experience and previous training in paediatric resuscitation, many
      candidates lacked the basic knowledge necessary for the resuscitation of
      seriously ill or injured children. There was a significant improvement in this
      knowledge after the course, and this was maintained for 4 months. The paediatric
      life-support course is an important means of resuscitation training for junior
      doctors.

PMID- 12047691
TI  - Sepsis in neonatal intensive care in the late 1990s.
AB  - AIM: To determine the incidence and clinical characteristics of sepsis in
      ventilated infants from an Australian neonatal intensive care unit (NICU) in the
      late 1990s. METHODS: Demographic data was collected from babies requiring
      assisted ventilation (AV) over the 6-month period from 1 July to 31 December
      1998. Sepsis was divided into early onset sepsis (EOS; " 72 h of age) and late
      onset sepsis (LOS; >72 h of age), including both definite (culture-proven +
      abnormal markers) and probable (culture negative + abnormal markers) episodes.
      RESULTS: Two hundred and eleven babies required AV over this period. Of these, 64
      (30.3%) had at least one infection, with 85 episodes of sepsis (40.3 episodes per
      100 admissions requiring AV). There were 22 babies with 22 episodes of EOS, and
      45 with 63 episodes of LOS. Three babies had both EOS and LOS. The rate of EOS
      was 10.4 infected infants (10.4 infections per 100 admissions requiring AV). The
      rate of LOS was 21.3 infected infants (29.9 infections per 100 admissions
      requiring AV). The rates of both EOS and LOS were higher than previously reported
      by Australian studies in the early 1990s. In both EOS and LOS, risk factors for
      infection were common. Group B streptococcus was the commonest cause of definite
      EOS. The mortality rate from sepsis in the EOS group was 14% (3/22). Coagulase
      negative staphylococci were the commonest cause of LOS. The mortality rate from
      sepsis in the LOS group was 11% (5/45). CONCLUSIONS: EOS and LOS are significant
      problems in ventilated NICU infants in the late 1990s.

PMID- 12047692
TI  - Survey of the use of complementary medicines and therapies in children with
      asthma.
AB  - OBJECTIVE: To survey the frequency of use of complementary medicines (CM) and
      complementary therapies (CT) in asthmatic children. METHODOLOGY: A 3-month survey
      of asthmatic inpatients and outpatients of a teaching hospital respiratory
      paediatrician was undertaken. Parents answered a structured questionnaire about
      their past and present usage and opinions of CM and CT. Parents and the physician
      independently assessed overall asthma control. 'Users' and 'non-users' of CM and
      CT were compared for characteristics of asthma, usage of conventional medications
      and parental demographics. RESULTS: One hundred and seventy-four children with
      331 parents were enrolled in the study. All of the children were on
      bronchodilators and 150 (86.2%) were on disodium cromoglycate or inhaled
      steroids. Control was assessed by a physician as good in 95 children (54.6%),
      fair in 65 (37.4%) and poor or very poor in 13 (7.5%). Ninety (51.7%) of the
      children had used at least one CM in their lifetime. Out of the 145 preparations
      used, 90 (62.1%) were in current use. Vitamins and minerals (53.2%) and herbal
      preparations (29%) were used most commonly. Only 47.8% of parents had told their
      doctors about the use of CM. Costs ranged from $A2-$A200 (median $A10) per month.
      Forty-three (24.7%) of the children had been taken to an alternative practitioner
      at a cost of $A25-$A400 (median $A40) per month. Users of CM and CT were
      significantly more likely than non-users to have persistent asthma (P < 0.02), be
      on high-dose inhaled or oral steroids (P < 0.05), to have poor or very poor
      control of symptoms (P < 0.04), and more frequent doctor visits (P < 0.05). They
      also had more adverse reactions to relieving bronchodilators (P < 0.02) and were
      significantly older than non-users (P < 0.02). The most common reasons for using
      CM and CT were dissatisfaction with conventional therapies and concerns about
      steroid side-effects. CONCLUSIONS: Health professionals should be aware of the
      high rates of usage of CM and CT in asthmatic children and of parental attitudes
      to conventional and alternative therapies.

PMID- 12047693
TI  - Tracheobronchography and angiocardiography of paediatric cardiac patients with
      airway disorders.
AB  - OBJECTIVE: We report our experience in combining tracheobronchography and
      angiocardiography in the assessment of a selected cohort of paediatric cardiac
      patients with problematic airway disorders. METHODOLOGY: The clinical records of
      11 patients who underwent 17 studies at a median age of 5.5 months (range 3
      months to 10.8 years) were reviewed. Tracheobronchography and angiocardiography
      were performed under general anaesthesia using a non-ionic contrast agent. The
      findings were compared with those of flexible bronchoscopy and magnetic resonance
      imaging (MRI). RESULTS: Seven patients had cardiac lesions associated with
      vascular anomalies potentially compressing the airway, while four had no
      identifiable aberrant or enlarged vessels. All examinations but one were
      performed without complications. Tracheobronchography demonstrated extrinsic
      vascular compression with secondary airway malacia in three (27%), intrinsic
      tracheobronchial stenosis in five (45%), and airway malacia in three patients
      (27%). Precise measurement of the airway calibre and real-time fluoroscopic
      monitoring facilitated transcatheter tracheobronchial interventions (six balloon
      dilations, three stent implantations) in four patients. In conjunction with
      angiocardiography, cine-tracheobronchography provided detailed information on the
      spatial relationship between vascular and airway structures in all patients;
      allowed dynamic assessment of airway malacia; and facilitated preoperative
      planning in six patients. In contrast, bronchoscopy failed to differentiate
      malacia from extrinsic compression in four patients (36%), while MRI, performed
      in six patients, was unsatisfactory in one due to a motion artefact and failed to
      diagnose airway malacia and extrinsic compression in three patients. CONCLUSIONS:
      Tracheobronchography is relatively safe in paediatric cardiac patients. Combined
      tracheobronchography and angiocardiography, a less operator-dependent imaging
      modality compared to bronchoscopy and MRI, delineated the airway and vascular
      anatomy in detail; facilitated preoperative planning; and permitted transcatheter
      tracheo-bronchial interventions. The dynamic capability of tracheobronchography
      supplements that of flexible bronchoscopy and MRI in the diagnosis of airway
      malacia.

PMID- 12047694
TI  - Transfusion in premature infants impairs production and/or release of red blood
      cells, white blood cells and platelets.
AB  - OBJECTIVE: To examine whether red blood cell transfusion in infants with anaemia
      of prematurity alters peripheral counts of red blood cell precursors, total white
      blood cells and white cell differential and platelets. METHODOLOGY: In 18
      consecutive stable premature infants with anaemia of prematurity, peripheral cell
      counts were prospectively recorded immediately before transfusion of 20 mL/kg
      packed red blood cells (given over 6 h), and at 48 h after completion of the
      transfusion. RESULTS: The median (interquartile range) haematocrit increased from
      22.0% (21.3-24.0%) pre-transfusion to 37.0% (36.0-38.0%) post-transfusion (P <
      0.001). Red-cell precursors decreased: median (interquartile range) reticulocytes
      from 3.7% (3.0-7.7%) to 3.7% (2.6-4.1%) (P = 0.03); and median (interquartile
      range) nucleated red blood cells from 0 G/L (0-0.2 G/L) to 0 G/L (0-0 G/L) (P =
      0.03). The mean (SD) platelet count decreased from 420 G/L (154 G/L) to 313 G/L
      (101 G/L) (P = 0.001). The total white blood cell count and neutrophils did not
      change significantly; however, median (interquartile range) immature neutrophils
      decreased from 0.12 G/L (0.06-0.74 G/L) to 0.08 G/L (0.01-0.24 G/L) (P = 0.03).
      Lymphocytes, eosinophils, basophils and plasma cells remained unchanged.
      Monocytes increased (P = 0.01). CONCLUSIONS: Forty-eight hours after red blood
      cell transfusion to premature infants, there is an absolute decrease in red blood
      cell precursors, immature white blood cells and platelets, probably due to
      erythropoietin-suppression.

PMID- 12047695
TI  - Effect of low versus normal birthweight on menarche in 14-year-old Polish girls.
AB  - OBJECTIVE: The relationship between intrauterine growth retardation and sexual
      maturation has not been completely established. The aim of the present study was
      to compare menarche in 14-year-old Polish girls of low and normal birthweight,
      along with an evaluation of the impact of socio-economic status and body mass
      index (BMI). METHODS: We studied 1060 girls (177 pre- and 883 post-menarche) aged
      13.5-14.5 years. These girls attended the 7th grade of randomly selected primary
      schools in Wroclaw, Poland. The BMI was used as a measurement of general
      adiposity. The cut-off value of the 10th percentile of birthweight for
      gestational age was used to differentiate between girls born small for
      gestational age (SGA) and girls with a birthweight appropriate to gestational age
      (AGA). Parental education level and other measures were used to assess socio
      economic status (SES). RESULTS: Birthweight (OR = 2.54; 95% CI 1.22-5.28) and BMI
      at the age of 14 years (OR = 7.93; 95%CI 4.67-13.48) were factors affecting the
      onset of menarche among the 14-year-old girls. CONCLUSION: Polish girls born
      small for gestational age are more likely to have experienced menarche by the age
      of 14 years, compared with their peers of normal weight at birth. These findings
      seem to be consistent with the hypothesis that the age of menarche is, to some
      extent, set by patterns of gonadotropin release, established prior to birth.
      Additionally, the age of menarche varies depending on levels of fat accumulation
      during childhood and adolescence.

PMID- 12047697
TI  - Symptomatic fracture incidence in those under 50 years of age in southern
      Tasmania.
AB  - OBJECTIVE: To document symptomatic fracture incidence in those aged under 50
      years of age. METHODS: Fractures were ascertained from X-ray reports containing
      the word 'fracture' from all radiology providers for the geographically defined
      population of southern Tasmania (n = 165 175) for the period 1 July 1997 to 30
      June 1999. RESULTS: In the 2-year study frame there were 2943 fractures in 164
      730 person years in males and 1348 fractures in 165 620 person years in females.
      This represents a fracture incidence of 1787 per 100 000 person years in males
      and 819 per 100 000 person years in females. Peak fracture incidence was 10-14
      years in females and 15-19 years in males although different fracture types had
      varying peak incidence suggesting different fracture-specific causes. The most
      common fractures were those of the hand (24%), forearm (17%), wrist (10%) and
      foot (9%). All fractures (including vertebral) were more common in males with
      relative risks ranging from 1.34 to 4.50. The estimated probability of at least
      one fracture between birth and 50 years of age was 59% for males and 34% for
      females. CONCLUSION: There are threefold as many fractures in this age group
      compared to those due to osteoporosis in the elderly in any given year. More
      research priority needs to be given to understanding the causes of these
      fractures so that preventive strategies can be formulated.

PMID- 12047696
TI  - Early-onset neonatal group B streptococcal infections in New Zealand 1998-1999.
AB  - OBJECTIVE: To determine in New Zealand infants the attack rates, risk factors,
      preventive policies, strain serotype and antibiotic susceptibilities of early
      onset neonatal group B streptococcus (GBS) infection. METHOD: A 2-year
      prospective active surveillance study was conducted in New Zealand's 19 neonatal
      units. Cases had to present within 48 h of delivery, be unwell, possess abnormal
      haematological indices and have GBS isolated from sterile sites. RESULTS: Of the
      112 402 infants born in New Zealand during 1998-1999, 56 had early-onset GBS
      infection, an attack rate of 0.5 per 1000 live births (95% confidence interval
      [CI] 0.38, 0.65). Seven had meningitis and there was one death (case fatality
      rate of 1.8%; upper 95% CI 9.5%). Univariate analysis identified young maternal
      age, parity, preterm labour, prolonged membrane rupture, maternal fever and
      assisted delivery as risk factors. Preventive policies for GBS were reported by
      14 (74%) obstetric centres associated with neonatal units. Of the 56 cases, five
      (9%) were born to mothers receiving intrapartum antibiotics, 32 (57%) had mothers
      with risk factors but were not treated with antibiotics, and 19 (34%) were born
      to mothers without identifiable risk factors for GBS prevention. Serotypes Ia and
      III predominated, while two isolates were resistant to erythromycin and/or
      clindamycin. CONCLUSIONS: Rates of early-onset GBS infection are similar to other
      countries following the introduction of prevention policies. Further reductions
      are possible with full implementation of these guidelines. Meanwhile, emergence
      of antibiotic resistance complicates the management of women with penicillin
      allergy. Vaccine development therefore remains a priority.

PMID- 12047698
TI  - Asthma in children: gaps between current management and best practice.
AB  - OBJECTIVES: To determine the extent to which steps three to six of the Australian
      six-step asthma management plan are being implemented in the community and to
      identify barriers to the adoption of best practice asthma management. METHODS: A
      cross-sectional descriptive study was conducted at the Royal Children's Hospital
      and Sunshine Hospital, Melbourne. Two hundred and thirty-one 2-5-year old
      children who visited the emergency department for asthma were enrolled in the
      study. Main outcome measures were frequency of asthma management practices and
      barriers, as measured by parent-completed questionnaire. RESULTS: Gaps: 51% of
      parents do not feel they have enough information about asthma triggers, more than
      60% of children with persistent or frequent episodic asthma are not using regular
      preventive medication, 48% do not have a written action plan, 39% have not had
      their asthma reviewed in the last 6 months, and 38% of parents do not feel that
      they have enough information about their child's asthma. Areas where current
      practice was close to best practice: 83% of doctors had talked to parents about
      what causes or 'triggers' their child's asthma, less than 1% of children are
      using puffers without a spacer, 83% of parents who had an action plan used it for
      the current visit to the emergency department. CONCLUSIONS: Large gaps still
      exist between current management and best practice in this group of emergency
      department attenders. Improvements in asthma management could be achieved if the
      child's asthma doctor requested review visits for asthma, provided an action plan
      and followed best practice in relation to asthma medications.

PMID- 12047699
TI  - Staphylococcus aureus bacteraemia in children: a 5-year retrospective review.
AB  - OBJECTIVE: The clinical presentation of Staphyloccocus aureus bacteraemia has
      been well described in adults, but there is a paucity of published data on the
      presentation of S. aureus bacteraemia in children. This review sought to compare
      the presentation of S. aureus in children with that of adults. METHODS: We
      conducted a 5-year retrospective chart review of S. aureus bacteraemia at the
      Royal Alexandra Hospital for Children between 1994 and 1998. RESULTS: Of the 140
      episodes of S. aureus bacteraemia, 53% were community acquired and 47%
      nosocomially acquired. The clinical presentation of S. aureus bacteraemia in the
      children in the present study differed significantly from published studies of
      adult patients. Of children with community-acquired bacteraemia without pre
      existing medical conditions, 59% had a bone or joint infection, which is higher
      than adult series. Endocarditis has been associated with up to 30% of community
      acquired bacteraemia in adults but was much less frequent (1.4%) in the present
      study. Despite the infrequent use of empiric antibiotic therapy (34% of
      episodes), the case fatality rate (1.4%) was significantly lower than the
      published literature relating to adults (11-32%). CONCLUSION: The present study
      highlights the differences between S. aureus bacteraemia in adults and children.

PMID- 12047700
TI  - Chronic fatigue syndrome: successful outcome of an intensive inpatient programme.
AB  - OBJECTIVE: To study the outcome of adolescents with chronic fatigue syndrome
      (CFS) following an intensive multi-disciplinary inpatient programme. METHODS: A
      follow-up questionnaire was distributed to all 57 adolescents who had completed
      the CFS inpatient programme at the Austin and Repatriation Medical Centre.
      RESULTS: Forty-two adolescents (74%) returned follow-up questionnaires.
      Immediately following the programme and up to five years after the programme, the
      majority of participants had returned to school and were functioning better in
      terms of physical activity and social interactions as compared with before the
      programme. Before the programme, 94% of adolescents were attending school half
      time or less. Up to 5 years after the programme, 78% of adolescents were
      attending school full-time or with occasional absences only. CONCLUSIONS: A
      multidisciplinary inpatient programme for CFS was successful in helping to
      rehabilitate this group of adolescents who were significantly incapacitated prior
      to entering the inpatient programme.

PMID- 12047701
TI  - Sample size.

PMID- 12047702
TI  - Lemierre syndrome due to non-multiresistant methicillin-resistant Staphylococcus
      aureus.

PMID- 12047703
TI  - Bone marrow transplantation for beta-thalassaemia major by an HLA-mismatched
      parent.
AB  - A six-year-old boy was diagnosed with beta-thalassaemia major during infancy.
      Since then, he required monthly blood transfusion and irregular iron chelation
      therapy. He had hepatosplenomegaly and elevated liver enzymes; the serum ferritin
      was up to 3800 ng/mL. An echocardiogram showed left-ventricular enlargement. His
      one-antigen-mismatched mother was chosen as a bone marrow donor. He was
      pretreated with intensive red blood cell transfusion and hydroxyurea for 6 weeks
      prior to conditioning. The conditioning included total body irradiation (300
      cGy), busulfan (14 mg/kg), cyclophosphamide (160 mg/kg) and anti-thymocyte
      globulin (rabbit; 90 mg/kg). Marrow cell dose was 5.4 x 108/kg. Graft versus host
      disease (GVHD) prophylaxis included cyclosporine A (CSA) and methylprednisolone.
      Neutrophil engraftment occurred on day 23. Grade II acute GVHD occurred on day
      45. The patient developed complications including septicaemia, haemorrhagic
      cystitis, intracranial haemorrhage and heart failure. He subsequently recovered
      from the complications without sequelae. The patient remained transfusion
      independent at a follow-up examination after 18 months. This case suggested that
      a mismatched family member may be considered as a bone marrow donor for beta
      thalassaemia major. In places where conventional treatment is not feasible, for
      example, in China, this approach may be an alternative option. A more intensive
      immunosuppressive regimen and a higher marrow cell dose may be important for
      successful engraftment. High-dose anti-thymocyte globulin may also prevent severe
      GVHD.

PMID- 12047704
TI  - Mycobacterium ulcerans infection diagnosed by polymerase chain reaction.
AB  - Mycobacterium ulcerans infection is the third most important mycobacterial
      infection world-wide affecting immunocompetent individuals and causes chronic
      progressive skin ulcers. It has been described in many different regions world
      wide. The diagnosis of M. ulcerans infection is often delayed because the
      diagnosis is difficult to make when new cases appear outside known endemic areas.
      However, molecular methods are now available to diagnose and distinguish M.
      ulcerans from other mycobacteria, allowing rapid diagnosis. Presented here is the
      case of a previously well girl from Townsville, Queensland, with extensive M.
      ulcerans infection involving the elbow joint, triceps tendon and underlying bone.
      Rapid diagnosis by polymerase chain reaction confirmed M. ulcerans infection.
      This is the first known case of M. ulcerans infection from Townsville in over 25
      years, highlighting the changing epidemiology of this disease.

PMID- 12047705
TI  - Familial parathyroid carcinoma in a child.
AB  - Familial hyperparathyroidism and parathyroid carcinoma are rare diseases. A case
      of parathyroid carcinoma in an 8-year-old girl whose mother had previously
      undergone parathyroidectomy for primary hyperparathyroidism is reported.
      Parathyroid carcinoma in a preadolescent child has not been described previously,
      and may have a familial basis.

PMID- 12047706
TI  - Fryns syndrome: a surviving case with associated Hirschsprung's disease and
      hemidiaphragmatic agenesis.
AB  - Fryns syndrome is a rare autosomal recessive disorder of multiple congenital
      abnormalities. Major diagnostic criteria include congenital diaphragmatic hernia,
      distal limb and nail hypoplasia and abnormal facies. More than 70 cases have been
      reported since the first report in 1979, 86% of which have been associated with
      an early lethal outcome. We report the case of a survivor who also has associated
      Hirschsprung's disease. On review of previously reported cases, defects of
      neuronal migration may be more common than previously recognized. The
      diaphragmatic hernia was repaired in two stages with a silastic patch followed by
      a reversed latissimus dorsi muscle flap.

PMID- 12047707
TI  - The Western Australian register for autism spectrum disorders.

PMID- 12047708
TI  - Nasogastric rehydration does have a role in acute paediatric bronchiolitis.

PMID- 12047709
TI  - A prospective study of children with community-acquired needlestick injuries in
      Melbourne.

PMID- 12047717
TI  - Leptin uptake by serotonergic neurones of the dorsal raphe.
AB  - The effects of leptin on food intake, metabolism, sleep patterns and reproduction
      may be mediated, in part, by the midbrain serotonergic systems. Here, we report
      on the distribution of neurones that accumulate leptin in the raphe nuclei of
      male and female rats after intracerebroventricular administration of mouse
      recombinant leptin labelled with digoxigenin. Direct leptin-targeted cells were
      present in the periventricular grey, pontine and raphe nuclei. Confocal
      microscopy revealed that raphe neurones which accumulated leptin were
      predominantly serotonergic. The temporal pattern of leptin accumulation by raphe
      neurones showed a marked gender difference: 6 h after leptin administration, all
      male and female rats showed massive leptin binding in the dorsal raphe, while 30
      min after leptin treatment, only 10% of male rats exhibited leptin-labelled cells
      in contrast to 50% of females. The present observations reveal that leptin can be
      selectively accumulated by serotonergic neurones in the raphe nuclei and that
      this mechanism is gender specific. These findings support the idea that the
      midbrain serotonergic system is an important mediator of the effects of leptin on
      brain function and may provide an explanation for gender differences in
      metabolism regulation and its coordination with higher functions of the brain.

PMID- 12047718
TI  - Increased galanin synapses onto activated gonadotropin-releasing hormone neuronal
      cell bodies in normal female mice and in functional preoptic area grafts in
      hypogonadal mice.
AB  - Galanin synaptic input onto gonadotropin-releasing hormone (GnRH) neuronal cell
      bodies was analysed in female mice using the presynaptic vesicle-specific
      protein, synaptophysin (Syn) as a marker. In the first experiment, forebrain
      sections from normal ovariectomized ovarian steroid-primed mice exhibiting a
      surge of luteinizing hormone were processed for immunohistochemical labelling for
      GnRH, synaptophysin, galanin and Fos. Two representative sections from each
      brain, one passing through the anterior septum (anterior section) and the other
      through the organum vasculosum lamina terminalis-preoptic area (posterior
      section), were analysed under the confocal microscope. None of the GnRH cells
      analysed in the anterior sections were Fos immunoreactive (IR) or received input
      from galanin-IR fibres. In contrast, the majority of GnRH cells in the posterior
      sections analysed were Fos-positive. The number of galanin synapses onto the Fos
      positive GnRH cells was significantly higher than that in the Fos-negative cells
      in this area of the brain, even though the number of Syn-IR appositions was
      comparable to each other. Transplantation of preoptic area (POA) into the third
      cerebral ventricle of hypogonadal (HPG) mice corrects deficits in the
      reproductive system. In the second experiment, synaptic input to GnRH cells was
      compared between HPG/POA mice with (functional graft) or without (nonfunctional
      graft) gonadal development. The mean numbers of Syn-IR appositions and galanin
      synapses per GnRH cell and the proportion of GnRH cells with galanin input were
      significantly higher in the functional than in the nonfunctional grafts. The
      results suggest that galanin can act directly on the GnRH cell bodies and may
      have an important regulatory role on the GnRH system.

PMID- 12047719
TI  - Response to male odours in progestin receptor- and oestrogen receptor-containing
      cells in female rat brain.
AB  - Sensory cues from male rats, such as odours and vaginal-cervical stimulation
      (VCS), play a modulatory role in female rat sexual behaviour. For example,
      exposure to male odours and VCS appears to be at least partially responsible for
      increases in sexual behaviour following repeated mating of oestradiol-primed
      female rats. Although there is evidence that VCS influences sexual behaviour via
      a ligand-independent progestin receptor (PR)-dependent mechanism, the mechanism
      by which odours influence sexual behaviour is not known. We tested the hypothesis
      that, similar to VCS, the effects of male odours on sexual behaviour are mediated
      by progestin receptors. Female rats were injected with the progestin antagonist,
      RU486, or oil vehicle and were then exposed to male-soiled bedding or clean
      bedding. Although exposure to male-soiled bedding resulted in higher levels of
      Fos immunoreactivity in brain areas associated with female sexual behaviour, the
      progestin antagonist did not reduce this effect. Furthermore, there was minimal
      coexpression of odour-induced Fos and progestin receptors in brain areas
      associated with female sexual behaviour. Together, these results suggest that the
      effects of male odours are not mediated by a PR-dependent mechanism. Therefore,
      we tested the hypothesis that oestrogen receptor (ER)-containing cells are
      involved in the effects of olfactory cues. Although there was virtually no
      coexpression of ERbeta and odour-induced Fos in brain areas associated with
      female sexual behaviour, exposure to male odours slightly increased the number of
      cells coexpressing ER(alpha) and odour-induced Fos in the posterodorsal medial
      amygdala. Although, these results do not support the hypothesis that the effects
      of odours are mediated by a PR-dependent mechanism, they suggest that integration
      of male odours and hormonal cues may occur in ER(alpha)-containing cells in the
      posterodorsal medial amygdala.

PMID- 12047720
TI  - Maternal regulation of the hypothalamic-pituitary-adrenal axis in the 20-day-old
      rat: consequences of laboratory weaning.
AB  - There is a large body of evidence that the development of the hypothalamic
      pituitary-adrenal (HPA) system in the rat is under maternal regulation. One
      method used to study the influence of the dam-pup interaction in neonates and
      weanlings is the separation of mother and litter for 24 h. Previous studies
      showed that, even at the time of weaning, maternal deprivation results in a
      dysregulation of the HPA axis at multiple levels. However, the maternal
      deprivation paradigm usually includes deprivation of food and water, and it was
      not clear to which extent the observed effects are due to either maternal cues or
      dehydration and fasting. The primary purpose of the present study was to
      determine the role of fasting and/or maternal separation on the HPA axis at the
      time of weaning. Pups at 20 days after parturition are capable of self-feeding
      and no longer require tactile stimulation to induce eliminative functions. The
      results indicated that 24 h of fasting led to increased basal levels and further
      increases in stress induced corticosterone secretion. Fasting also appeared to
      contribute to the down regulation of basal glucocorticoid receptor mRNA in the
      hippocampus. In contrast, abrupt weaning irrespective of fasting or dehydration
      resulted in a suppressed adrenocorticotropin hormone response to an injection of
      isotonic saline. Although there was an effect of maternal separation on
      corticotropin-releasing factor mRNA in the paraventricular nucleus, this effect
      was further exacerbated by the absence of food. Finally, all rats that were
      separated from their dams showed more efficient negative-feedback. Thus,
      different aspects of the HPA system appear to respond differentially to either
      the absence of food or the absence of the mother or both.

PMID- 12047721
TI  - Comparison of somatostatin receptor expression in human gliomas and
      medulloblastomas.
AB  - The expression of the five somatostatin receptor subtypes, sst1-5 was compared on
      tissue containing glial tumours (glioblastomas or oligodendrogliomas),
      medulloblastomas, and on normal human cortex. By semiquantitative reverse
      transcription coupled to polymerase chain reaction, the receptor expression
      profiles were high in cortex and in tissue containing oligodendrogliomas. It was
      moderate in medulloblastomas. Tissue containing glioblastomas displayed lower
      expression of somatostatin receptor subtypes, sst1 and sst3 being mostly
      expressed. By 125I-Tyr0DTrp8 somatostatin-14 or 125I-Leu8DTrp22 Tyr25
      somatostatin-28 autoradiography combined with synaptophysin immunohistochemistry,
      it was possible to differentiate between isolated tumoral cell component
      infiltrating the cerebral parenchyma (cortex or white matter) and tumoral tissue
      (without residual parenchyma) in glioblastomas or oligodendrogliomas. Glial
      tumoral tissue per se presented few somatostatin receptors. By contrast,
      medulloblastoma tumoral cells exhibited numerous octreotide sensitive
      somatostatin receptors. sst2 immunocytochemistry demonstrated immunostaining of
      neuronal cells and neuropile; sst2 and sst3 immunostaining was identified on
      glioblastoma proliferating vessels endothelial cells and on medulloblastomas
      tumoral cells. Faint sst2 immunostaining among glial tumoral cells was due to
      microglia, while glioma cells did not significantly stain. In summary,
      medulloblastoma tumoral cells express sst2/sst3 receptors at a high level while
      glioma cells do not. In gliomas, sst expression is restricted to endothelial
      cells on proliferating vessels (displaying both sst2 and sst3 receptors),
      including parenchyma and reactive microglia (only sst2). The differential
      expression of sst2/sst3 receptors on gliomas and medulloblastomas has
      implications for the therapy of these tumours.

PMID- 12047722
TI  - The affinity and activity of the multiple hormone response element in the
      proximal promoter of the human oxytocin gene.
AB  - In vivo there appears to be a marked association between oestrogen levels and the
      expression of the oxytocin (OT) gene in most tissues. Transfection and DNA
      protein binding experiments using high levels of either oestrogen receptor
      (ER)alpha or ERbeta imply a direct interaction of these transcription factors
      with the multiple hormone response element (HRE) at approximately -160 from the
      transcription start site of the OT gene in most species. In an extensive set of
      experiments, we show, using both transfection and protein-DNA binding, that low
      to moderate amounts of either oestrogen receptor, while being able to interact
      directly with a classic oestrogen response element (ERE) fail to interact with
      the human OT -160 HRE. Instead, this element, similar to its bovine counterpart,
      has a high affinity for the orphan receptors steroidogenic factor 1 and chicken
      ovalbumin upstream promoter transcription factor. Second, the human and bovine OT
      promoter can be made artificially responsive towards oestrogen in a
      cotransfection system over-expressing ERalpha or ERbeta, but not in cells
      expressing natural levels of these steroid receptors. Interestingly, nuclear
      extracts from both ERalpha-positive MCF7 cells and ERalpha-negative MDA-MB231
      cells both contain a transcription factor which binds specifically to both the
      hOT-HRE element and to a classic ERE, and which has orphan receptor-like binding
      properties rather than those of an oestrogen receptor. Together, these and other
      results suggest that oestrogen action in vivo on the OT gene in all species is
      more likely to involve a DNA-independent mechanism than classic direct
      interactions with dimeric oestrogen receptors.

PMID- 12047723
TI  - Butyl benzyl phthalate, an endocrine disrupter, inhibits pulsatile luteinizing
      hormone secretion under an insulin-induced hypoglycaemic state in ovariectomized
      rats.
AB  - Butyl benzyl phthalate (BBP) and bisphenol A (BPA), termed endocrine disrupters,
      are known to mimic oestrogen in their actions, and therefore there is concern
      about their effect on reproductive functions. Since it is reported that the
      inhibitory action of oestrogen on the pulsatile secretion of luteinizing hormone
      (LH) is enhanced under insulin-induced hypoglycaemia, whether this also applies
      to BBP and BPA was examined in the present study. In adult ovariectomized (OVX)
      rats, the pulsatile LH secretion 24 h after subcutaneous injection of 10 mg BBP
      (BBP-treated), 10 mg BPA (BPA-treated) or 100 ng 17beta-oestradiol (E2-treated),
      all of which were dissolved in sesame oil, was not changed significantly compared
      to that after the injection of sesame oil only. Furthermore, in oil-treated OVX
      rats, the pulsatile LH secretion immediately after intravenous injection of
      insulin (1.0 U) was not changed compared to that after saline injection. In BBP
      treated OVX rats, the injection of insulin (1.0 U) significantly decreased the
      number of LH pulses as in E2-treated OVX rats. The injection of insulin did not
      significantly affect the amplitude of LH pulses in BBP-, BPA- and E2-treated OVX
      rats. The results indicate that the oestrogenic action of BBP is significantly
      enhanced by insulin-induced hypoglycaemia and thus the pulsatile LH secretion is
      inhibited. We suggest that weak oestrogenic endocrine disrupters may become
      harmful to reproductive functions even in adult female rats, if acting under a
      low energy state.

PMID- 12047724
TI  - Chronic neuropeptide Y Y5 receptor stimulation suppresses reproduction in virgin
      female and lactating rats.
AB  - Continuous infusion of neuropeptide Y (NPY) disrupts cyclicity and delays the
      onset of puberty in female rats indicating that NPY can suppress reproduction.
      Central application of NPY also reliably increases food intake in rats. States
      with heavy demands on energy resources where reproduction is also inhibited, such
      as lactation, are similarly accompanied by elevations in central NPY expression.
      In previous studies, we have shown that, compared to lactating rats fed ad
      libitum, food-restricted lactating rats exhibit a longer period of lactational
      diestrus that is correlated with increased central NPY expression. These studies
      link NPY to the inhibition of reproduction that is mediated by low availability
      of energy resources. Here, we examine the effect of chronic 7-day infusion of the
      mixed Y1/Y4/Y5 agonist (Leu31, Pro34) NPY and selective agonists to the Y2 (NPY13
      36) and Y5 (D-Trp32 NPY and D-Trp34 NPY) receptors on food intake and the
      oestrous cycle of virgin female rats. We also investigated the effect of chronic
      infusion from day 8-15 postpartum (pp) of D-Trp32 NPY and D-Trp34 NPY on food
      intake and the length of lactational diestrus in lactating rats fed ad libitum.
      In virgin females, infusion of (Leu31, Pro34) NPY and both the Y5 agonists
      lengthened the period between consecutive oestrus days while the Y2 agonist NPY13
      36 was without effect. Selective Y5 receptor activation alone caused an increase
      in food intake in virgin females. In lactating females, D-Trp32 NPY extended the
      length of lactational diestrus, while D-Trp34 NPY had no effect on this
      parameter. These data suggest that Y5 receptor activation suppresses the
      reproductive axis in both virgin and lactating rats and that Y5 receptor
      activation enhances food-intake in virgin females.

PMID- 12047725
TI  - Coregulator proteins and corticosteroid action in the brain.
AB  - The corticosteroid hormones cortisol and corticosterone are secreted by the
      adrenal gland in response to stress. They have profound effects on brain
      function, which are mediated by the related mineralocorticoid (MR) and
      glucocorticoid (GR) receptors. The MR and GR are ligand-activated transcription
      factors and exert different, sometimes opposing effects on the brain. The balance
      between these two receptor activities is considered essential for appropriate
      corticosteroid signalling and health. An exciting recent insight in steroid
      biology is that the nature and magnitude of steroid receptor-mediated responses
      depend not only on ligand and receptor availability, but also in a critical
      manner on the presence of downstream mediator proteins (coregulators), such as
      the steroid receptor coactivators and nuclear receptor corepressors. Members of
      the coregulator families differ in their specific interactions with steroid
      receptors, as well as in their distribution throughout the brain and pituitary.
      The activity of these proteins can be regulated both at the expression level, and
      by post-translational modifications. These characteristics make coregulator
      proteins of outstanding interest as determinants of receptor, cell and state
      dependent effects of MR and GR signalling (and steroid receptor signalling in
      general) in the brain.

PMID- 12047726
TI  - Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal
      axes.
AB  - Under normal conditions, the adrenal glucocorticoids, the endproduct of the
      hypothalamic-pituitary-adrenal (HPA) axis, provide a frontline of defence against
      threats to homeostasis (i.e. stress). On the other hand, chronic HPA drive and
      glucocorticoid hypersecretion have been implicated in the pathogenesis of several
      forms of systemic, neurodegenerative and affective disorders. The HPA axis is
      subject to gonadal influence, indicated by sex differences in basal and stress
      HPA function and neuropathologies associated with HPA dysfunction. Functional
      cross-talk between the gonadal and adrenal axes is due in large part to the
      interactive effects of sex steroids and glucocorticoids, explaining perhaps why
      several disease states linked to stress are sex-dependent. Realizing the
      interactive nature by which the hypothalamic-pituitary-gonadal and HPA systems
      operate, however, has made it difficult to model how these hormones act in the
      brain. Manipulation of one endocrine system is not without effects on the other.
      Simultaneous manipulation and assessment of both endocrine systems can overcome
      this problem. This dual approach in the male rat reveals that testosterone can
      act and interact on different aspects of basal and stress HPA function. Basal
      adrenocorticotropic hormone (ACTH) release is regulated by testosterone-dependent
      effects on arginine vasopressin synthesis, and corticosterone-dependent effects
      on corticotropin-releasing hormone (CRH) synthesis in the paraventricular nucleus
      (PVN) of the hypothalamus. In contrast, testosterone and corticosterone interact
      on stress-induced ACTH release and drive to the PVN motor neurones. Candidate
      structures mediating this interaction include several testosterone-sensitive
      afferents to the HPA axis, including the medial preoptic area, central and medial
      amygdala and bed nuclei of the stria terminalis. All of these relay homeostatic
      information and integrate reproductive and social behaviour. Because these
      modalities are affected by stress in humans, a dual systems approach holds great
      promise in establishing further links between the neuroendocrinology of stress
      and the central bases of sex-dependent disorders, including psychiatric,
      cardiovascular and metabolic disease.

PMID- 12047727
TI  - Alcohol-related discussions during general medicine appointments of male VA
      patients who screen positive for at-risk drinking.
AB  - OBJECTIVE: This study describes primary care discussions with patients who
      screened positive for at-risk drinking. In addition, discussions about alcohol
      use from 2 clinic firms, one with a provider-prompting intervention, are
      compared. DESIGN: Cross-sectional analyses of audiotaped appointments collected
      over 6 months. PARTICIPANTS AND SETTING: Male patients in a VA general medicine
      clinic were eligible if they screened positive for at-risk drinking and had a
      general medicine appointment with a consenting provider during the study period.
      Participating patients ( N = 47) and providers ( N = 17) were enrolled in 1 of 2
      firms in the clinic (Intervention or Control) and were blinded to the study
      focus. INTERVENTION: Intervention providers received patient-specific results of
      positive alcohol-screening tests at each visit. MEASURES AND MAIN RESULTS: Of 68
      visits taped, 39 (57.4%) included any mention of alcohol. Patient and provider
      utterances during discussions about alcohol use were coded using Motivational
      Interviewing Skills Codes. Providers contributed 58% of utterances during alcohol
      related discussions with most coded as questions (24%), information giving (23%),
      or facilitation (34%). Advice, reflective listening, and supportive or affirming
      statements occurred infrequently (5%, 3%, and 5%, of provider utterances
      respectively). Providers offered alcohol-related advice during 21% of visits.
      Sixteen percent of patient utterances reflected "resistance" to change and 12%
      reflected readiness to change. On average, Intervention providers were more
      likely to discuss alcohol use than Control providers (82.4% vs 39.6% of visits; P
      =.026). CONCLUSIONS: During discussions about alcohol, general medicine providers
      asked questions and offered information, but usually did not give explicit
      alcohol-related advice. Discussions about alcohol occurred more often when
      providers were prompted.

PMID- 12047728
TI  - Mutual mistrust in the medical care of drug users: the keys to the "narc"
      cabinet.
AB  - OBJECTIVE: Caring for patients who are active drug users is challenging. To
      better understand the often difficult relationships between illicit drug-using
      patients and their physicians, we sought to identify major issues that emerge
      during their interactions in a teaching hospital. DESIGN: Exploratory qualitative
      analysis of data from direct observation of patient care interactions and
      interviews with drug-using patients and their physicians. SETTING: The inpatient
      internal medicine service of an urban public teaching hospital. PARTICIPANTS:
      Nineteen patients with recent active drug use, primarily opiate use, and their 8
      physician teams. RESULTS: Four major themes emerged. First, physicians feared
      being deceived by drug-using patients. In particular, they questioned whether
      patients' requests for opiates to treat pain or withdrawal might result from
      addictive behavior rather than from "medically indicated" need. Second, they
      lacked a standard approach to commonly encountered clinical issues, especially
      the assessment and treatment of pain and opiate withdrawal. Because patients'
      subjective report of symptoms is suspect, physicians struggled to find criteria
      for appropriate opiate prescription. Third, physicians avoided engaging patients
      regarding key complaints, and expressed discomfort and uncertainty in their
      approach to these patients. Fourth, drug-using patients were sensitive to the
      possibility of poor medical care, often interpreting physician inconsistency or
      hospital inefficiency as signs of intentional mistreatment. CONCLUSION:
      Physicians and drug-using patients in the teaching hospital setting display
      mutual mistrust, especially concerning opiate prescription. Physicians' fear of
      deception, inconsistency and avoidance interacts with patients' concern that they
      are mistreated and stigmatized. Medical education should focus greater attention
      on addiction medicine and pain management.

PMID- 12047729
TI  - Outpatient treatment entry and health care utilization after a combined
      medical/substance abuse intervention for hospitalized medical patients.
AB  - CONTEXT: Drug-abusing patients utilize extensive amounts of health services
      resources, yet the acute medical hospitalization has typically not been used
      effectively to engage patients in substance abuse treatment. OBJECTIVES: To
      assess the effect of an integrated substance abuse/acute medical care day
      hospital (DH) intervention. DESIGN AND SETTING: Prospective, consecutive chart
      review of patients referred to a day hospital program from the medicine service
      at an urban tertiary care teaching hospital. From the referral cohort, a
      comparison group receiving usual care was identified. PARTICIPANTS: One hundred
      twenty adult medicine inpatients with active substance abuse and self-identified
      motivation to enter treatment. MAIN OUTCOME MEASURES: Outpatient substance abuse
      treatment entry and post-intervention health services utilization. RESULTS:
      Following DH treatment, 50.6% entered further outpatient substance abuse
      treatment (vs 2.4% comparison patients; P <.001). There was a significant
      increase in ambulatory medical visits for DH patients (pre-6 month 0.49 vs post-6
      month 3.46; P <.001), greater than the change noted for comparison patients.
      However, there was no difference noted in pre-post hospitalization or emergency
      department utilization following the DH intervention. CONCLUSIONS: A DH program
      for substance abusing hospitalized medicine patients that introduces substance
      abuse treatment during treatment for an acute medical illness does appear to
      improve outpatient substance abuse treatment entry and ambulatory care
      utilization after hospital discharge.

PMID- 12047730
TI  - The impact of needle exchange-based health services on emergency department use.
AB  - OBJECTIVE: To examine the impact of the New Haven Community Health Care Van
      (CHCV), a mobile needle exchange-based health care delivery system, in reducing
      emergency department (ED) use among out-of-treatment injection drug users (IDUs)
      between January 1, 1996 and December 31, 1998. DESIGN: A pre-post comparison of
      ED utilization was performed using linked medical records from New Haven's only
      two emergency departments. Fixed-effect negative binomial regression analysis was
      used to explore the impact of the CHCV on ED use within a longitudinal cohort.
      SETTING: Mobile health clinic in New Haven, Conn. PARTICIPANTS: Out-of-treatment
      IDUs. INTERVENTION: Acute care, linkages to medical, drug treatment, and social
      services. MEASUREMENTS AND MAIN RESULTS: Among 373 IDUs, 117 (31%) were CHCV
      clients, and 256 had not used CHCV services. At baseline, CHCV users were more
      frequent users of ED services (P <.001). After full-scale implementation, mean ED
      utilization declined among CHCV clients and increased within the non-CHCV group.
      CHCV use is associated with statistically significant reductions in ED use, with
      an incidence rate ratio (IRR) of 0.79 (95% confidence interval [95% CI], 0.66 to
      0.95). Subgroup analyses demonstrated significant IRR reductions, notably among
      Hispanics (0.65; 95% CI, 0.47 to 0.90), men (0.79; 95% CI, 0.64 to 0.98], HIV
      negative IDUs (0.79; 95% CI, 0.63 to 0.98), and those with mental illness (0.75;
      95% CI, 0.60 to 0.94). CONCLUSION: Needle exchange-based health care services can
      reduce ED utilization among high-risk injection drug users. Such services may
      have an important role within communities with high rates of drug use and
      HIV/AIDS.

PMID- 12047732
TI  - Investigation of a brief teaching encounter using standardized patients: teaching
      residents alcohol screening and intervention.
AB  - OBJECTIVE: To investigate a brief teaching intervention using standardized
      patients (SPs) trained to improve residents' detection and advising of problem
      drinkers. DESIGN: Pretest-posttest design assessing resident behavior and skills.
      SUBJECTS: Nineteen internal medicine residents in a University Hospital General
      Internal Medicine Clinic. INTERVENTION: Announced SPs were interviewed by
      residents and presented to faculty who provided brief instruction on the National
      Institute on Alcohol Abuse and Alcoholism guidelines for screening and brief
      counseling of problem drinkers. MEASURE: Unannounced SPs assessed resident
      behavior and skills. RESULTS: Following the teaching intervention, 2 times more
      residents screened for alcohol use and nearly 3 times more residents did brief
      counseling. Residents reported that the intervention was informative and
      valuable. CONCLUSION: A single, 1-hour teaching intervention lead to a 2- to 3
      fold increase in resident detection and advising of problem drinkers. SPs provide
      effective teaching encounters and a useful measure of resident behavior.

PMID- 12047731
TI  - The effects of carbamazepine and lorazepam on single versus multiple previous
      alcohol withdrawals in an outpatient randomized trial.
AB  - OBJECTIVE: Benzodiazepines are the mainstay of treatment for mild-to-moderate
      alcohol withdrawal in outpatient settings, but they can interact with alcohol,
      cause motor incoordination, or be abused. This study compared the therapeutic
      responses of the benzodiazepine lorazepam and the anticonvulsant carbamazepine
      for the outpatient treatment of acute alcohol withdrawal in terms of patients'
      previous detoxification histories, and compared the effects of these 2
      medications on drinking behaviors in the immediate postdetoxification period.
      DESIGN: This was a randomized double-blind trial comparing patient responses to
      carbamazepine and lorazepam across 2 levels of detoxification histories (0-1 or
      >or=2 previous medicated detoxifications). SETTING: A university medical center
      substance abuse clinic in Charleston, SC. PATIENTS: One hundred thirty-six
      patients in moderate alcohol withdrawal were randomized. Major exclusions were
      significant hepatic or hematologic abnormalities and use of medications that
      could alter withdrawal symptoms. INTERVENTIONS: Patients received 600-800 mg of
      carbamazepine or 6-8 mg of lorazepam in divided doses on day 1 tapering to 200 mg
      of carbamazepine or 2 mg of lorazepam. MAIN OUTCOME MEASURES: The Clinical
      Institute Withdrawal Assessment for Alcohol-Revised was used to assess alcohol
      withdrawal symptoms on days 1 through 5 and postmedication at days 7 and 12.
      Daily drinking was measured by patient report using a daily drinking log and a
      breath alcohol level with each visit. Side effects were recorded daily. RESULTS:
      Carbamazepine and lorazepam were equally effective at decreasing the symptoms of
      alcohol withdrawal. In the post-treatment period, 89 patients drank on at least 1
      day; on average, carbamazepine patients drank less than 1 drink per drinking day
      and lorazepam patients drank almost 3 drinks per drinking day (P =.003). Among
      those with multiple past detoxifications, the carbamazepine group drank less than
      1 drink per day on average and the lorazepam group drank about 5 drinks per day
      on average (P =.033). Lorazepam-treated patients had a significant rebound of
      alcohol withdrawal symptoms post-treatment (P =.007) and the risk of having a
      first drink was 3 times greater (P =.04) than for carbamazepine-treated patients.
      Twenty percent of lorazepam-treated patients had dizziness, motor incoordination,
      or ataxia and did not recognize their impairment. Twenty percent of carbamazepine
      treated patients reported pruritus but no rash. CONCLUSIONS: Carbamazepine and
      lorazepam were both effective in decreasing the symptoms of alcohol withdrawal in
      relatively healthy, middle-aged outpatients. Carbamazepine, however, was superior
      to lorazepam in preventing rebound withdrawal symptoms and reducing post
      treatment drinking, especially for those with a history of multiple treated
      withdrawals.

PMID- 12047734
TI  - Smoking cessation in a homeless population: there is a will, but is there a way?
AB  - This cross-sectional study sought to determine the prevalence of smoking,
      readiness to quit, and preferences for smoking cessation treatments among a
      sample of 236 homeless adults attending 9 sites serving homeless persons (mean
      age 41.8 years; 73% male). Two thirds (69%) were current smokers, of whom 37%
      reported readiness to quit smoking within the next 6 months. In bivariate
      analyses, persons were significantly (P <.05) more likely to be ready to quit if
      they had tried to quit in the past and if they had social support to quit
      smoking. Nicotine replacement was the most commonly preferred assistance method
      (44%), and self-efficacy to quit (10-point scale) was significantly greater if
      assistance was available (7.3 vs 4.9; P <.001). The findings suggest an urgent
      need to develop and implement smoking cessation programs for homeless persons.

PMID- 12047733
TI  - Policy progress for physician treatment of opiate addiction.
AB  - Medical treatment of heroin addiction with methadone and other pharmacotherapies
      has important benefits for individuals and society. However, regulatory policies
      have separated this treatment from the medical care system, limiting access to
      care and contributing to the social stigma of even effective addiction
      pharmacotherapy. Increasing problems caused by heroin addiction have added
      urgency to the search for policies and programs that improve the access to and
      quality of opiate addiction treatment. Recent initiatives aiming to reintegrate
      methadone maintenance and other addiction pharmacotherapies into medical practice
      may promote both expanded treatment capacity and increased physician expertise in
      addiction medicine. These initiatives include changes in federal oversight of the
      opiate addiction treatment system, the approval of physician office-based
      methadone maintenance programs for stabilized patients, and federal legislation
      that could enable physicians to treat opiate addiction with new medications in
      regular medical practice.

PMID- 12047735
TI  - Professional satisfaction experienced when caring for substance-abusing patients:
      faculty and resident physician perspectives.
AB  - This survey aimed to describe and compare resident and faculty physician
      satisfaction, attitudes, and practices regarding patients with addictions. Of 144
      primary care physicians, 40% used formal screening tools; 24% asked patients'
      family history. Physicians were less likely (P <.05) to experience at least a
      moderate amount of professional satisfaction caring for patients with alcohol
      (32% of residents, 49% of faculty) or drug (residents 30%, faculty 31%) problems
      than when managing hypertension (residents 76%, faculty 79%). Interpersonal
      experience with addictions was common (85% of faculty, 72% of residents) but not
      associated with attitudes, practices, or satisfaction. Positive attitudes toward
      addiction treatment (adjusted odds ratio [AOR], 4.60; 95% confidence interval
      [95% CI], 1.59 to 13.29), confidence in assessment and intervention (AOR, 2.49;
      95% CI, 1.09 to 5.69), and perceived responsibility for addressing substance
      problems (AOR, 5.59; CI, 2.07 to 15.12) were associated with greater
      satisfaction. Professional satisfaction caring for patients with substance
      problems is lower than that for other illnesses. Addressing physician
      satisfaction may improve care for patients with addictions.

PMID- 12047736
TI  - Impact of active drug use on antiretroviral therapy adherence and viral
      suppression in HIV-infected drug users.
AB  - Despite a burgeoning literature on adherence to HIV therapies, few studies have
      examined the impact of ongoing drug use on adherence and viral suppression, and
      none of these have utilized electronic monitors to quantify adherence among drug
      users. We used 262 electronic monitors to measure adherence with all
      antiretrovirals in 85 HIV-infected current and former drug users, and found that
      active cocaine use, female gender, not receiving Social Security benefits, not
      being married, screening positive for depression, and the tendency to use alcohol
      or drugs to cope with stress were all significantly associated with poor
      adherence. The strongest predictor of poor adherence and, in turn, failure to
      maintain viral suppression, was active cocaine use. Overall adherence among
      active cocaine users was 27%, compared to 68% among subjects who reported no
      cocaine use during the 6-month study period. Consequently, 13% of active cocaine
      users maintained viral suppression, compared to 46% of nonusers. Interventions to
      improve adherence should focus on reducing cocaine use, developing adaptive
      coping skills, and identifying and treating depression.

PMID- 12047737
TI  - Decreased alcohol consumption in outpatient drinkers is associated with improved
      quality of life and fewer alcohol-related consequences.
AB  - This study's objective was to determine whether changes in alcohol consumption
      are associated with changes in quality of life and alcohol-related consequences
      in an outpatient sample of drinkers. Two hundred thirteen subjects completed the
      Short Form 36-item (SF-36) Health Survey and the Short Inventory of Problems at
      baseline, 6 months, and 12 months. Subjects who sustained a 30% or greater
      decrease in drinks per month reported improvement in SF-36 Physical Component
      Summary (P =.058) and Mental Component Summary (P =.037) scores and had fewer
      alcohol-related consequences (P <.001) when compared to those with a <30%
      decrease. These findings suggest another benefit of alcohol screening and
      intervention in the primary care setting.

PMID- 12047739
TI  - Substance abuse: the expanding role of general internal medicine.

PMID- 12047740
TI  - Internal medicine and alcohol: time to move forward.

PMID- 12047738
TI  - Alcohol use disorders in primary care: do gender-specific differences exist?
AB  - OBJECTIVE: To describe how alcohol use disorders (AUDs) affect women, focusing on
      gender-specific implications for primary care physicians (PCPs). DESIGN: An
      overview of literature from 1966 to 2000 identified by a medline, PsychINFO and
      HealthSTAR/Ovid Healthstar database search using key words "women,""alcohol" and
      "alcoholism." MEASUREMENTS AND MAIN RESULTS: Although the prevalence of AUDs is
      greater in men than in women, women with AUDs are more likely to seek help, but
      less likely to be identified by their physicians. Psychiatric comorbidities
      (especially depression and eating disorders) are more common in women with AUDs
      than in men with AUDs. A past history of sexual and/or physical abuse places a
      woman at increased risk for AUDs. Women have a greater sensitivity to alcohol,
      have an accelerated progression from alcohol toxicity, and have increased
      mortality at lower levels of consumption compared to men. Women and men who are
      light-to-moderate drinkers have lower coronary artery disease mortality than do
      abstainers or heavy drinkers. Risk of breast cancer is increased in women who
      drink >or=1 drinks daily. Common barriers to treatment include: fear of
      abandonment by partner; fear of loss of children; and financial dependency. Brief
      interventions have been shown to be effective in reduction of alcohol consumption
      in women with at-risk drinking. It is unclear if women-only treatment programs
      improve outcomes. CONCLUSION: PCPs should be alert to gender-specific differences
      for women with AUDs.

PMID- 12047743
TI  - Getting to the guts of immune regulation.

PMID- 12047742
TI  - Qualitative differences between naive and memory T cells.

PMID- 12047744
TI  - T-cell activation occurs simultaneously in local and peripheral lymphoid tissue
      following oral administration of a range of doses of immunogenic or tolerogenic
      antigen although tolerized T cells display a defect in cell division.
AB  - How the mucosal immune system promotes active immunity against harmful organisms
      but tolerance to commensal bacteria or dietary antigens is poorly understood.
      Thus, the antigen-presenting cell (APC), site of antigen presentation, and
      effector mechanisms responsible for oral priming and tolerance remain unclear.
      Characterizing differences between oral priming and tolerance may improve the
      exploitation of oral tolerance for therapeutic applications and aid the design of
      oral vaccines. To address these questions we compared the mucosal and systemic
      activation and localization of antigen-specific T cells during the induction of
      oral priming and tolerance. Activation marker expression and cell division by tg
      T cells was determined in conjunction with their anatomical location. These
      studies show that after feeding, T cells are activated in both peripheral and
      local lymphoid tissues within 6 hr, irrespective of the presence of adjuvant.
      Subsequently, T-cell accumulation can be detected simultaneously in peripheral
      and mesenteric lymph nodes and Peyer's patches within 24 hr of feeding, but only
      after 3 days post feeding in the lamina propria. Primed and tolerized T cells
      adopted similar phenotypes as assessed by activation marker expression. However,
      within the mesenteric lymph nodes (MLN) tolerized T cells underwent significantly
      fewer divisions than primed T cells. Thus, T-cell activation and expansion occurs
      throughout the animal after feeding a range of doses of antigen, irrespective of
      whether priming or tolerance is the eventual outcome. However, the presence of an
      adjuvant enhances clonal expansion in the MLN while tolerized T cells display
      defective cell division.

PMID- 12047745
TI  - Characterization of guinea-pig group 1 CD1 proteins.
AB  - CD1 molecules are cell-surface glycoproteins with strong structural similarities
      to major histocompatibility complex (MHC) class I molecules, and studies in
      humans and mice have demonstrated that CD1 proteins perform the unique role of
      presenting lipid antigens to T lymphocytes. Our previous studies have shown that
      guinea-pigs, unlike the muroid rodents, have an extended family of group 1 CD1
      genes. In the current study, we raised monoclonal anibodies (mAbs) against guinea
      pig CD1 proteins and generated transfected cell lines expressing individual
      members of the guinea-pig CD1 family. Our results indicated that multiple members
      of the guinea-pig CD1 family, including members that are homologous to the human
      CD1b and CD1c proteins, are expressed at the protein level in transfected cells
      and in specialized antigen-presenting cells such as monocyte-derived dendritic
      cells. In addition, CD1 proteins, especially guinea-pig CD1b3, were expressed on
      a large number of B cells in the guinea-pig, and CD1 expression appeared to be
      regulated by B-cell maturation or differentiation. Interestingly, three different
      patterns of intracellular localization were observed for the various guinea-pig
      CD1 isoforms, a finding that is reminiscent of the distinct patterns of
      intracellular localization that have been previously demonstrated for human CD1a,
      CD1b and CD1c. Taken together, these results provide further evidence for
      substantial similarities between the guinea-pig and human CD1 systems, thus
      supporting the possibility that the guinea-pig may offer significant advantages
      as an animal model for the study of the in vivo role of CD1 proteins in
      infectious and autoimmune diseases.

PMID- 12047746
TI  - Murine NFX.1: isolation and characterization of its messenger RNA, mapping of its
      chromosomal location and assessment of its developmental expression.
AB  - We have previously isolated (by expression cloning) a human cDNA, termed NFX.1,
      encoding a nucleic acid-binding protein that interacts with the conserved X1 box
      cis-element first discovered in class II major histocompatibility complex (MHC)
      genes. Functional studies involving expression of NFX.1 and assessment of
      expression from class II reporter constructs and endogenous class II MHC genes
      indicated that the factor could repress transcription of class II MHC genes.
      Subsequent studies have extended the biological significance of the factor,
      indicating that it plays an important role in neuronal development. Indeed, the
      reiterated RING finger motifs in the central domain of the polypeptide strongly
      suggest that NF-XI is a probable E3 ubiquitin protein ligase, indicating that the
      protein may have multiple activities. Here we report the cloning of the mouse
      homologue of the human NfX.1 cDNA: m-Nfx.1. Comparison of the deduced primary
      sequence of mouse and human NFX.1 proteins shows very high homology and confirms
      that m-NFX.1 contains the conserved cysteine-rich DNA-binding motif first
      described in human NFX.1 (95% homology). Expression of MHC class II genes is
      substantially reduced following expression of m-NFX.1, which confirms that we
      have isolated the functional murine homologue of human NfX.1 cDNA. Further
      evidence comes from the mapping of m-Nfx.1 gene to the proximal region of mouse
      chromosome 4, a region syntenic to the location of human Nfx.1 (short arm of
      chromosome 9). Expression profiling shows that m-NFX.1 is expressed ubiquitously
      in both adult tissues and during development, supporting the hypothesis that it
      may have yet-undescribed roles in distinct biological processes.

PMID- 12047747
TI  - Interactions formed by individually expressed TAP1 and TAP2 polypeptide subunits.
AB  - The transporter associated with antigen processing (TAP) supplies peptides into
      the lumen of the endoplasmic reticulum (ER) for binding by major
      histocompatibility complex (MHC) class I molecules. TAP comprises two
      polypeptides, TAP1 and TAP2, each a 'half-transporter' encoding a transmembrane
      domain and a nucleotide-binding domain. Immunoprecipitation of rat TAP1 and TAP2
      expressed individually in the human TAP-deficient cell line, T2, revealed that
      both bound the endogenously expressed HLA-A2 and -B51 class I molecules. Using
      HLA-encoding recombinant vaccinia viruses HLA-A*2501, -B*2704, -B*3501 and 
      B*4402, alleles also associated with both TAP1 and TAP2. Thus, TAP1 and TAP2 do
      not appear to differ in their ability to interact with MHC class I alleles.
      Single TAP polypeptide subunits also formed MHC class I peptide-loading
      complexes, and their nucleotide-binding domains retained the ability to interact
      with ATP, and may permit the release of peptide-loaded MHC class I molecules in
      the absence of a peptide transport cycle. It is also demonstrated by chemical
      cross-linking that TAP2, but not TAP1, has the ability to form a homodimer
      complex both in whole cells and in detergent lysates. Together these data
      indicate that single TAP polypeptide subunits possess many of the features of the
      TAP heterodimer, demonstrating them to be useful models in the study of ATP
      binding cassette (ABC) transporters.

PMID- 12047748
TI  - Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood.
AB  - CD4(+) CD25(+) regulatory T cells prevent organ-specific autoimmune diseases in
      various animal models. We analysed human lymphoid tissues to identify similar
      CD25(+) regulatory T cells. Adult peripheral blood contained two populations of
      CD4(+) T cells that expressed CD25 at different densities. The larger population
      (approximately 40%) expressed intermediate levels of CD25 (CD25(+)) and displayed
      a memory T-cell phenotype (CD45RA-/RO(+), CD45RB(low), CD95(+), CD62L(low),
      CD38(low)). The smaller population of cells (approximately 2%) expressed very
      high levels of CD25 (CD25(++)). In addition to the activation/memory T-cell
      antigens mentioned above they also expressed intracellular CD152 (CTLA-4) as well
      as enhanced levels of cell-surface CD122, similar to the murine CD4(+) CD25(+)
      regulatory counterpart. To exclude that the CD25(++) cells had not been recently
      primed by external antigen we analysed cord blood and thymus. CD25(++), CD152(+)
      and CD122(++) cells were present in paediatric thymus (10% of CD4(+) CD8(-)
      thymocytes) expressing signs of recent selection (CD69+) and in cord blood (5% of
      CD4(+) cells) where they showed a naive phenotype. In addition, cord blood
      contained a small population of CD25(+) cells (approximately 2% of CD4 T cells)
      that were CD152(-) and CD122(low) and displayed signs of activation. Together
      with published data that CD25(+) CD25(++) cells from the thymus and peripheral
      blood are regulatory, our results suggest that regulatory CD25(+) T cells leave
      the thymus in a naive state and become activated in the periphery.

PMID- 12047749
TI  - Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB
      gene in Escherichia coli.
AB  - Activation of human Vgamma9/Vdelta2 T cells by many pathogens depends on the
      presence of small phosphorylated non-peptide compounds derived from the 2-C
      methyl-d-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. We here
      demonstrate that in Escherichia coli mutants deficient in lytB, an essential gene
      of the MEP pathway, a potent Vgamma9/Vdelta2 T-cell activator accumulates by a
      factor of approximately 150 compared to wild-type E. coli. The compound
      responsible for the strong immunogenicity of this E. coli mutant was subsequently
      characterized and identified as a small pyrophosphorylated metabolite, with a
      molecular mass of 262 Da, derived from the MEP pathway. Stimulation of human
      peripheral blood mononuclear cells (PBMC) with extracts prepared from the lytB
      deficient E. coli mutant led to upregulation of T-cell activation markers on the
      surface of Vgamma9/Vdelta2 T cells as well as proliferation and expansion of
      Vgamma9/Vdelta2 T cells. This response was dependent on costimulatory growth
      factors, such as interleukin (IL)-2, IL-15 and IL-21. Significant levels of
      interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were
      secreted in the presence of IL-2 and IL-15, but not in the presence of IL-21,
      demonstrating that proliferating phosphoantigen-reactive Vgamma9/Vdelta2 T cells
      do not necessarily produce proinflammatory cytokines.

PMID- 12047750
TI  - Interleukin-7 inhibits pre-T-cell differentiation induced by the pre-T-cell
      receptor signal and the effect is mimicked by hGM-CSF in hGM-CSF receptor
      transgenic mice.
AB  - We have previously reported that human granulocyte-macrophage colony-stimulating
      factor (hGM-CSF) causes a stage-specific inhibition of T-cell receptor (TCR)
      alphabeta cell development in the thymus of transgenic mice constitutively
      expressing the hGM-CSF receptor. Since it has been reported that the addition of
      interleukin-7 (IL-7) to fetal thymic organ culture (FTOC) has similar effects, we
      compared the effects of IL-7 and hGM-CSF on TCR(alphabeta) cell development in
      hGM-CSF receptor transgenic mice. We reconstituted fetal lobes with sorted pre-T,
      or post pre-T CD4(-)CD8(-) precursor cells. The addition of either IL-7 or hGM
      CSF to these cultures suppressed further differentiation of pre-T cells but not
      post pre-T cells. At the same time, the cell number was increased, suggesting
      that pre-T-cell proliferation is stimulated by these cytokines. Furthermore, the
      differentiation of recombination-activating gene-1 (RAG-1)-deficient pre-T cells
      in response to anti-CD3 antibody stimulation was suppressed by either IL-7 or hGM
      CSF, suggesting that these cytokines inhibit the pre-T-cell receptor (pre-TCR)
      signal. This inhibition is unexpected because the pre-TCR signal and the IL-7
      signal have previously been considered to be co-operative. Recent analysis of the
      downstream events of IL-7 receptor and GM-CSF receptor revealed that they share
      common signal transduction molecules. Our results show that IL-7 is able to
      promote pre-T cell proliferation and to suppress differentiation induced by the
      pre-TCR signal. GM-CSF can mimic these biological activities of IL-7 when the pre
      T cells express GM-CSF receptors. Our data suggest that both timing and level of
      activation of the IL-7 signalling pathway must be precisely regulated to
      facilitate the differentiation of thymocytes.

PMID- 12047751
TI  - Impaired germinal centre formation and humoral immune response in the absence of
      CD28 and interleukin-4.
AB  - The generation of an optimal humoral immune response requires fully activated T
      cells. For complete activation at least two signals are needed. The first one is
      an antigen dependent one via the T cell receptor, the second one is a
      costimulatory signal which can be delivered by the CD28 molecule after binding to
      CD80 (B7.1) or CD86 (B7.2). Fully activated T helper cells are competent to
      deliver help to B-cells by secreting cytokines (e.g. interleukin (IL)-4) or up
      regulating CD40 ligand for proliferation and differentiation of B cells. These
      interactions mainly take place in germinal centres (GC) that arise after antigen
      stimulation in B cell-follicles of peripheral lymphatic tissues and are the sites
      of massive B-cell proliferation, affinity maturation and class switch. The roles
      of CD28 and IL-4 were investigated in GC formation and antibody production. A
      markedly diminished humoral immune response was observed in IL-4(-/-) xCD28(-/-)
      mice whereas in CD28(-/-) and IL-4(-/-) mice the defect was less severe.
      Especially the formation of germinal centres was significantly reduced in CD28(-/
      ) or IL-4(-/-) mice and almost undetectable in IL-4(-/-) xCD28(-/-) mice. Taken
      together these data indicate that CD28 and IL-4 are synergistically involved in
      GC formation and immunoglobulin production.

PMID- 12047752
TI  - Regulation of major histocompatibility complex class II synthesis by interleukin
      10.
AB  - We have shown previously that interleukin-10 (IL-10) blocks the development and T
      cell stimulatory capacity of human monocyte-derived dendritic cells, without
      apparently down-regulating the surface expression of co-stimulatory molecules or
      human leucocyte antigen (HLA) molecules. In the majority of donors (60%), the
      cell surface levels of HLA-DR actually increased upon IL-10 treatment. Here we
      have shown that IL-10 does not regulate HLA-DR transcription as assessed by
      polymerase chain reation. Epifluorescence microscopy analysis showed that IL-10
      primarily increased the intracellular pool of HLA-DR. In fact, IL-10 directly
      increased HLA-DR protein synthesis. However, IL-10 did not significantly alter
      the synthesis of invariant chain (Ii), which plays a crucial role in the
      assembly, transport and loading of newly formed HLA class II molecules, nor the
      amount of Ii reaching the cell-surface. In contrast, IL-10 increased the amount
      of HLA-DR-bound Iip33 shortly after the HLA-DR complex assembly. We postulate
      that, upon IL-10 treatment, immature Ii-associated HLA II molecules can still
      transit to the cell surface as they do in immature dendritic cells and recycle to
      the intracellular space, where they accumulate. A higher proportion of Ii
      associated HLA-DR, coupled to increased membrane recycling, may contribute to the
      lower T-cell stimulatory capacity of IL-10-treated dendritic cells.

PMID- 12047753
TI  - Genetic fusion of human insulin B-chain to the B-subunit of cholera toxin
      enhances in vitro antigen presentation and induction of bystander suppression in
      vivo.
AB  - The pentameric B-subunit of cholera toxin (CTB) can be used as an efficient
      mucosal carrier of either immunogenic or tolerogenic T-cell epitopes. In this
      study a series of fusions was constructed between the genes encoding CTB and the
      B-chain of human insulin (InsB). The resulting fusion proteins were expressed in
      Escherichia coli and isolated as cytoplasmic inclusion bodies that were then
      dissolved and assembled in vitro. GM1 enzyme-linked immunosorbent assay (ELISA),
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western
      blot analyses showed that the protein construct in which InsB was fused to the C
      terminus of a CTB monomer (CI) assembled into structures that both bound to the
      receptor GM1 ganglioside and reacted with monoclonal antibodies to CTB and
      insulin. Fusion of InsB to the N-terminus of CTB resulted in protein that could
      not assemble into pentameric CTB. In vitro assays showed that the CI fusion
      protein was 300-fold more potent than native insulin at inducing interleukin-2
      (IL-2) production by an insulin-specific T-cell hybridoma. When administered
      orally, the CI fusion protein induced efficient immunological suppression of
      ovalbumin-specific T-cell responses in mice co-immunized parenterally with
      insulin and ovalbumin. These results demonstrate the stability, GM1 receptor
      binding activity and antigenic authenticity of the CI fusion protein as well as
      its ability to elicit insulin-specific T-cell responses in vitro. In addition, we
      demonstrate that the CI fusion protein induces efficient immunosuppression after
      oral administration, raising the possibility of using such constructs in the
      treatment of type-1 diabetes.

PMID- 12047754
TI  - The 52 000 MW Ro/SS-A autoantigen in Sjogren's syndrome/systemic lupus
      erythematosus (Ro52) is an interferon-gamma inducible tripartite motif protein
      associated with membrane proximal structures.
AB  - The 52 000 MW Ro/SS-A (Ro52) protein is a major target of autoantibodies in
      autoimmune conditions such as systemic lupus erythematosus and Sjogren's
      syndrome. Recent genomic and bioinformatic studies have shown that Ro52 belongs
      to a large family of related RING/Bbox/coiled-coil (RBCC) tripartite motif
      proteins sharing overall domain structure and 40-50% identity at the amino acid
      level. Ro52 also has a B30.2 domain at the C-terminus. Using the human genome
      draft sequence, the genomic organization of the Ro52 gene on human chromosome
      11p15.5 has been deduced and related to the protein domain structure. We show
      that the steady-state levels of Ro52 mRNA are normally very low but are induced
      by cell activation with interferon-gamma. In transient transfection of HeLa
      cells, epitope-tagged Ro52 protein was localized to unidentified membrane
      proximal rod-like structures. Using in vitro coupled transcription/translation
      followed by immunoprecipitation, the autoimmune response to Ro52 protein was
      investigated and two distinct interactions were resolved. The Ro52 C-terminal
      B30.2 domain interacts with human immunoglobulin independently of antibody
      specificities. Sera derived from patients with Sjogren's syndrome and systemic
      lupus erythematosus, in addition, contained specific autoantibodies directed
      towards the rest of the Ro52 molecule. The majority of these autoimmune sera also
      immunoprecipitated the Ro52-related molecule RNF15. A possible role for Ro52
      protein in alterations of plasma membranes during cellular activation or
      apoptosis is discussed.

PMID- 12047755
TI  - The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary
      tuberculosis.
AB  - Prostaglandins (PG) are potent mediators of intercellular communication, and PGE2
      at high concentration is immunosuppressive for T-cell-mediated immunity. We
      studied the kinetics of PGE2 production and the expression of the enzymes related
      to its synthesis during the course of experimental pulmonary tuberculosis.
      Secondly, we analysed the pathological and immunological changes produced by the
      pharmacological suppression of PG production. In BALB/c mice infected via the
      trachea with Mycobacterium tuberculosis H37Rv there is an initial phase of
      partial resistance, dominated by type 1 cytokines plus tumour necrosis factor
      alpha (TNF-alpha) and expression of the inducible form of nitric oxide synthase
      (iNOS), followed by a phase of progressive disease. During the early phase of the
      infection some activated macrophages located in the alveolar-capillary
      interstitium and in granulomas showed strong PGE2 immunostaining. However, PGE2
      concentrations were relatively low and stable. Animals in this early phase of
      infection were treated with niflumic acid, a potent and specific blocker of cyclo
      oxygenase 2, the rate-limiting enzyme of PG production. In comparison with
      control animals, the suppression of PG synthesis produced higher inflammation and
      expression of TNF-alpha, interleukin-1alpha and interferon-gamma (IFN-gamma), but
      almost complete disappearance of iNOS expression, which coexisted with a
      significant increment of bacterial load. The late progressive phase in this
      experimental model is characterized by progressive pneumonia, small granulomas
      and diminished expression of IFN-gamma, TNF-alpha and iNOS in coexistence with
      high expression of IL-4. Strong PGE2 immunostaining was seen in foamy macrophages
      localized in the pneumonic areas, and the PGE2 concentration was four-fold higher
      in this late phase of infection than during the early phase. When PG production
      was suppressed in animals suffering advanced phase infection, a significant
      reduction of pneumonia and bacillus load with striking increment of granuloma
      size was seen, and the expression of IFN-gamma, TNF-alpha and iNOS was also
      improved. These findings demonstrate a significant participation of PGE2 in the
      pathogenesis of pulmonary tuberculosis, showing that during the early phase of
      the infection there are low PGE2 concentrations which contribute to iNOS
      expression permitting the temporal control of bacillus growth, while the high
      PGE2 concentrations during the late phase of the disease contribute to down
      regulate cell-mediated immunity, permitting disease progression.

PMID- 12047756
TI  - Antibody to Cryptococcus neoformans capsular glucuronoxylomannan promotes
      expression of interleukin-12Rbeta2 subunit on human T cells in vitro through
      effects mediated by antigen-presenting cells.
AB  - The results reported herein show that T cells responding to encapsulated
      Cryptococcus neoformans cells had reduced expression of interleukin-12 receptor
      beta2 (IL-12Rbeta2) in comparison to those responding to non-encapsulated cells.
      This suggested that encapsulation with glucuronoxylomannan (GXM), the principal
      constituent of the C. neoformans polysaccharide antiphagocytic capsule, inhibited
      expression of the IL-12Rbeta2 subunit on T cells responding to cryptococcal
      antigens. Addition of GXM-binding monoclonal antibody (mAb) overcame this effect
      by promoting IL-12Rbeta2 expression and by decreasing IL-1R expression on T
      cells. This effect may be a consequence of mAb-induced changes on antigen
      presenting cells (APC) that are closely related to increased phagocytosis.
      Blocking of phagocytosis with monoiodacetic acid (MIA) precluded up-regulation of
      B7 expression on APC and was associated with diminished IL-12Rbeta2 expression on
      T cells. The observed effects on T cells were interpreted as a consequence of
      increased APC function due to enhanced phagocytosis. These findings suggest a
      mechanism by which specific antibody can promote the polarization of the cellular
      immune response towards a Th1-like response and thus contribute to an enhanced
      cellular immune response against C. neoformans.

PMID- 12047759
TI  - Lymph nodes in gastric B-cell lymphoma: pattern of involvement and early
      histological changes.
AB  - AIMS: This study aims to analyse the histological pattern of nodal involvement in
      gastric B-cell lymphoma and to detect early involvement of the lymph nodes.
      METHODS AND RESULTS: Histological findings of 37 resected primary gastric
      lymphomas with 1313 regional lymph nodes were analysed. The primary tumour was
      classified into four groups: MALT lymphoma, MALT lymphoma with a minor large B
      cell lymphoma (<20%), large B-cell lymphoma with MALT lymphoma, and large B-cell
      lymphoma without MALT lymphoma. Histological patterns of nodal involvement were
      divided into sinusoidal, subsinusoidal/marginal, follicular, and diffuse
      patterns. Semi-nested polymerase chain reaction (PCR) analysis for IgH gene
      rearrangement was performed. Nodal involvement was found in 2/13 (15%) MALT
      lymphomas, 5/6 (83%) MALT lymphomas with a minor large B-cell lymphoma, 9/12
      (75%) large B-cell lymphomas with MALT lymphoma, and 6/6 (100%) large B-cell
      lymphomas without MALT lymphoma. The MALT lymphoma and MALT lymphoma with a minor
      large B-cell lymphoma showed a predominantly sinusoidal and subsinusoidal
      pattern, whereas diffuse pattern predominated in large B-cell lymphomas without
      MALT lymphoma and large B-cell lymphomas with MALT lymphoma. The follicular
      pattern was least common, being observed in 10.2% of large B-cell lymphomas
      without MALT lymphoma and large B-cell lymphomas with MALT lymphoma. Sinusoidal
      obliteration with permeation of small monocytoid cells into subsinusoidal zone is
      a characteristic finding suggesting early nodal involvement of MALT lymphoma.
      CONCLUSIONS: Histological patterns of nodal involvement in gastric B-cell
      lymphoma vary according to the histological grade. Immunostaining for CD20 with
      or without PCR analysis for IgH gene rearrangement would be a useful ancillary
      method to confirm lymphomatous involvement.

PMID- 12047757
TI  - Host responses to Renibacterium salmoninarum and specific components of the
      pathogen reveal the mechanisms of immune suppression and activation.
AB  - During infection, Renibacterium salmoninarum survives within the pronephric
      macrophages of salmonid fish. Therefore, to study the initial phases of the
      interaction we infected macrophages with live bacteria and analysed the responses
      of host and pathogen. It was found that the expression of msa encoding the p57
      antigen of R. salmoninarum, was constitutive, while the expression of hly and
      rsh, encoding haemolysins, and lysB and grp was reduced after infection.
      Macrophages showed a rapid inflammatory response in which the expression of
      interleukin-1beta (IL-1beta), major histocompatibility complex class II (MHC II),
      inducible cyclo-oxygenase (Cox-2), and inducible nitric oxide synthase (iNOS) was
      enhanced, but tumour necrosis factor-alpha (TNF-alpha) expression was greatly
      reduced initially and then increased. After 5 days, except for TNF-alpha and MHC
      II, expression returned to levels approaching those of uninfected macrophages. We
      propose that R. salmoninarum survives initial contact with macrophages by
      avoiding and/or interfering with TNF-alpha-dependent killing pathways. The
      effects of specific R. salmoninarum components were studied in vivo by injecting
      fish with DNA vaccine constructs expressing msa, hly, rsh, lysB, or grp. We found
      that msa reduced the expression of IL-1beta, Cox-2, and MHC II but stimulated TNF
      alpha while hly, rsh and grp stimulated MHC II but down-regulated TNF-alpha.
      Constructs expressing hly or lysB stimulated iNOS expression and additionally,
      lysB stimulated TNF-alpha. The results show how p57 suppresses the host immune
      system and suggest that the immune mechanisms for the containment of R.
      salmoninarum infections rely on MHC II- and TNF-alpha-dependent pathways.
      Moreover, prolonged stimulation of TNF-alpha may contribute to the chronic
      inflammatory pathology of bacterial kidney disease.

PMID- 12047760
TI  - Lipoblastoma-like tumour of the vulva: report of three cases of a distinctive
      mesenchymal neoplasm of adipocytic differentiation.
AB  - AIMS: We sought to delineate and describe three cases of a distinctive
      mesenchymal neoplasm of the vulva showing adipocytic differentiation and
      affecting young patients. METHODS AND RESULTS: In three patients between 13 and
      38 years of age, the vulvar tumours had well-circumscribed borders and ranged in
      size from 35 to 100 mm. Histologically, they were well circumscribed and
      lobulated. The lobules were separated by thin fibroconnective tissue septa and
      were composed of slender spindle cells showing slightly eosinophilic cytoplasm
      with indistinct boundaries, uniform nuclei with finely granular chromatin, and no
      nucleoli. The cells were embedded in a richly myxoid stroma. The background in
      all three tumours was a 'chicken-wire', capillary vascular network resembling
      that seen in myxoid liposarcomas. Two tumours had scattered signet-ring-type
      lipoblasts and the third a large number of such lipoblasts. Clusters of mature
      adipocytes were entrapped in the tumours. None had mitotic figures, necrosis, or
      pleomorphism. The neoplastic cells stained positively for vimentin and were
      negative for other immunohistochemical markers. Treatment for all three tumours
      was enucleation alone. After follow-up of 10 years, 7 years, and 1 year, all
      patients are well with no evidence of disease. CONCLUSIONS: The benign behaviour
      of these neoplasms militates against the diagnosis of liposarcoma. We believe
      these are benign lesions of adipocytic differentiation akin to infantile
      lipoblastomas.

PMID- 12047761
TI  - Sinonasal haemangiopericytoma-like tumour: a sinonasal glomus tumour or a
      haemangiopericytoma?
AB  - AIMS: Sinonasal haemangiopericytoma-like tumour is controversial with regard to
      its nosologic nature. This study aims to investigate its relationship with glomus
      tumour and haemangiopericytoma. METHODS AND RESULTS: Six cases of sinonasal
      haemangiopericytoma-like tumours identified in our files were reviewed for
      clinicopathological features, and compared with five cases each of soft tissue
      glomus tumour and meningeal haemangiopericytoma. Immunohistochemical studies for
      muscle-specific actin, smooth muscle actin, desmin and CD34 were performed.
      Sinonasal haemangiopericytoma-like tumour demonstrated a uniform histological
      appearance with bland-looking short, spindly cells forming sheets and short
      fascicles. The tumour cells were interspersed with slit-like, round and ectatic
      blood vessels. Actin immunoreactivity was demonstrated in all six cases, although
      occasionally patchy. The histological appearance and immunohistochemical
      phenotype of sinonasal haemangiopericytoma-like tumour were very similar to and
      focally indistinguishable from glomus tumour. Meningeal haemangiopericytoma, in
      contrast, was characterized by high tumour cellularity, random nuclear
      orientation, presence of staghorn vasculature and lack of immunohistochemical
      evidence of myogenic differentiation. CONCLUSIONS: We conclude that sinonasal
      haemangiopericytoma-like tumour is biologically close to or identical to glomus
      tumour, but is not related to haemangiopericytoma.

PMID- 12047762
TI  - Leiomyosarcoma of the head and neck: a clinicopathological study.
AB  - AIMS: The behaviour of leiomyosarcoma is site-related and there are few data on
      such tumours located in the head and neck. We studied the clinicopathological
      features of these lesions. METHODS AND RESULTS: Cases diagnosed as leiomyosarcoma
      of the head and neck were retrieved from the archives of three institutions.
      Immunohistochemistry was performed and follow-up information was obtained. There
      were seven men and six women, aged 21-73 years, and lesions involved the neck
      (n=3), maxilla (n=4), buccal area (n=3), and maxillary sinus, nose, and pharynx
      (n=1 each). Tumours ranged from 10 to 80 mm. All tumours showed at least focally
      typical histological features of leiomyosarcoma with perpendicularly arranged
      fascicles of smooth muscle cells with blunt-ended nuclei, eosinophilic cytoplasm
      and paranuclear vacuoles. They expressed muscle-specific actin (8/9), smooth
      muscle actin (7/9), and desmin (10/12). Follow-up information was available on
      nine patients. All had surgery, with radiation and/or chemotherapy in seven.
      Three (27%) recurred at 6-24 months; in one case twice. Five (56%) had
      metastases, including the three with prior recurrences at 1-128 months. Five
      (including two who received adjuvant therapy) were disease-free at a median of 47
      months, one was alive with metastatic disease at 24 months), and three were dead
      of disease (median 13 months). CONCLUSIONS: Head and neck leiomyosarcomas are
      rare and aggressive neoplasms which metastasize. Adjuvant therapy has limited
      effect.

PMID- 12047763
TI  - PTEN is not altered in sporadic vestibular schwannomas.
AB  - AIMS: To investigate the role of the tumour suppressor gene PTEN in the
      tumorigenesis and growth of sporadic vestibular schwannomas, and to characterize
      the cellular distribution of the PTEN protein in relation to the MIB-1
      proliferation index in these tumour. METHODS AND RESULTS: Immunoexpression of the
      PTEN protein was observed within the neoplastic Schwann cells in 21 out of 30
      sporadic schwannomas examined (70%). PTEN expression was consistently stronger in
      Antoni A areas than in Antoni B areas. High levels of PTEN immmunoexpression in
      schwannomas were associated with an increased MIB-1 labelling index.
      Occasionally, vascular endothelial cells also showed PTEN immunoreaction. By
      polymerase chain reaction-single strand conformation polymorphism screening, no
      mutations were found in the complete protein coding region of the PTEN gene.
      CONCLUSIONS: The PTEN tumour suppressor gene is expressed in the majority of
      sporadic schwannomas. The maintained expression of the PTEN protein, together
      with the lack of detectable mutations in this gene, suggests that the function of
      the PTEN tumour suppressor gene is not altered in sporadic vestibular
      schwannomas.

PMID- 12047764
TI  - Immunohistochemical detection of 8-hydroxydeoxyguanosine, a marker of oxidative
      DNA damage, in human chronic cholecystitis.
AB  - AIMS: Recent studies suggest that oxidative DNA damage induced during chronic
      inflammation may play a role in carcinogenesis in some organs. Although
      gallbladder carcinomas are frequently observed with a background of chronic
      cholecystitis, little is known about oxidative DNA damage in chronic
      cholecystitis. The aims of this study were to investigate the expression of 8
      hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal
      and chronically inflamed human gallbladder mucosa and compare its expression with
      clinicopathological findings. METHODS AND RESULTS: 8-OHdG expression was
      immunohistochemically examined using a monoclonal antibody against 8-OHdG in
      human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression
      was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of
      31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The
      positive cells were predominantly observed in the areas of active inflammation
      with prominent cell infiltration. Quantitative analysis revealed that the number
      of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated
      with the degree of the activity of mucosal inflammation, while gender, age, and
      the presence of gallstones did not influence the index. CONCLUSIONS: Oxidative
      DNA damage is common in chronic cholecystitis, suggesting a possible link between
      chronic inflammation and gallbladder carcinogenesis.

PMID- 12047765
TI  - Abnormal alpha-catenin expression in invasive breast cancer correlates with poor
      patient survival.
AB  - AIMS: alpha-Catenin is a member of the E-cadherin-catenin family of adhesion
      molecules whose role is essential for the function of the E-cadherin complex. In
      this study, we have evaluated the expression of alpha-catenin but also of the
      other catenins (beta-, gamma- and p120-catenin) and E-cadherin in invasive breast
      cancer and statistically analysed these expressions with known
      clinicopathological parameters, c-erbB-2 oncoprotein expression and patient
      survival. METHODS AND RESULTS: Abnormal E-cadherin and beta-catenin expression,
      especially loss of expression, was associated with lobular histological type of
      breast carcinomas (P=0.03 and P=0.01, respectively). Abnormal E-cadherin and
      alpha-catenin expression was associated with high histological grade ductal
      carcinomas (P=0.01 and P=0.03, respectively). Abnormal E-cadherin and beta
      catenin expression was correlated with lymph node metastases (P=0.02 and P=0.05,
      respectively), while abnormal alpha- and beta-catenin were correlated with the
      advanced stage of the disease (P=0.04 and P=0.05, respectively). Abnormal p120
      catenin expression was associated with loss of PR (P=0.008). Survival analysis
      demonstrated a statistically significant association between abnormal alpha
      catenin expression and poor patient survival (P=0.02). When survival analysis was
      performed according to the different patterns of abnormal expression,
      statistically significant associations were seen between cytoplasmic alpha- and
      beta-catenin expression and poor survival (P=0.006 and P=0.04, respectively).
      CONCLUSIONS: alpha-Catenin, especially its cytoplasmic expression, seems to be a
      more sensitive prognostic marker than the other members of the E-cadherin complex
      in invasive breast cancer.

PMID- 12047766
TI  - Genomic imbalances detected by comparative genomic hybridization are prognostic
      markers in invasive ductal breast carcinomas.
AB  - AIMS: The aim of this work is the study of the prognostic significance of the
      chromosomal aberrations described in a series of invasive ductal breast
      carcinomas. METHODS AND RESULTS: We analysed by comparative genomic hybridization
      a group of 70 formalin-fixed paraffin-embedded invasive ductal breast carcinomas.
      Aberrations showed a frequency similar to previous studies using frozen tumours.
      Interestingly, we identified gains involving 6q16-q24 more frequently than in
      other series. We analysed the association among the chromosomal imbalances, 11
      histopathological factors, relapse rate and overall survival of patients.
      Associations showed 16q losses as a potential marker of good prognosis, as they
      were more frequent in node-negative (P=0.025) and in oestrogen-positive tumours
      (P < 0.001). Furthermore, 100% of bcl-2+ tumours presented this aberration
      compared with 29.3% in bcl-2- (P=0.014). 1q, 11q, 17q and 20q gains were
      associated with poor prognosis: 95% of cases with 1q gains were bigger than 20 mm
      (P=0.041). Tumours with 1q and 11q gains showed a higher relapse rate (P=0.063;
      P=0.066). Within the good prognosis group of lymph node-negative patients, 17q
      and 20q gains identify a subgroup with increased relapse rate (P=0.039).
      CONCLUSIONS: Chromosomal imbalances, together with histopathological factors, may
      help to predict outcome in breast cancer patients.

PMID- 12047768
TI  - Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell
      carcinoma.
AB  - AIMS: The histopathological diagnosis of chromophobe renal cell carcinoma can
      present a diagnostic challenge, as these tumours can resemble either conventional
      renal cell carcinoma or oncocytoma. The aim of this study was to determine
      whether cytokeratin 7 expression is of practical use in the distinction of these
      three entities. METHODS AND RESULTS: A total of 40 cases previously diagnosed as
      either chromophobe renal cell carcinoma, conventional renal cell carcinoma or
      oncocytoma were identified. A representative section of each was stained with H&E
      and cytokeratin 7. Following independent review of the cases by three
      pathologists, a consensus diagnosis for each case was reached and the pattern of
      cytokeratin 7 staining was assessed. There were 12 cases of chromophobe renal
      cell carcinoma in the study, all of which showed a characteristic peripheral
      membrane pattern of staining for cytokeratin 7. Seventeen of the 18 cases of
      conventional renal cell carcinoma studied were negative for cytokeratin 7, while
      one case showed weak focal staining of <5% of the cells. The 10 cases of
      oncocytoma showed patchy weak to moderate cytoplasmic expression of cytokeratin
      7, without the characteristic peripheral membrane accentuation seen in the
      chromophobe carcinomas. CONCLUSIONS: Immunohistochemical staining for cytokeratin
      7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell
      carcinoma, and in distinguishing this tumour from both oncocytoma and
      conventional renal cell carcinoma.

PMID- 12047767
TI  - Wide spectrum screening keratin as a marker of metaplastic spindle cell carcinoma
      of the breast: an immunohistochemical study of 24 patients.
AB  - AIMS: Metaplastic spindle cell carcinomas may be difficult to distinguish
      histologically from other spindle cell lesions in the breast. Variable staining
      with cytokeratin immunomarkers has been reported for metaplastic carcinomas. We
      evaluated the diagnostic utility of anti-cytokeratin polyclonal antibody, wide
      spectrum screening keratin, to assess spindle cell breast lesions. METHODS AND
      RESULTS: Twenty-four patients with spindle cell breast carcinoma and 31 patients
      with benign or malignant spindle cell tumours were studied using a panel of
      antibodies directed against multiple cytokeratins (AE1/AE3, CAM5.2, wide spectrum
      screening keratin), epithelial membrane antigen (EMA), and vimentin. Sites of
      origin for the 31 controls included breast, bone, and soft tissue. All but one
      (95.8%) metaplastic carcinomas stained positively with wide spectrum screening
      keratin. Only rare or focal immunoreactivity was observed with AE1/AE3 in four
      cases; however, sensitivity of AE1/AE3 was improved in 13 cases using steam EDTA
      as an antigen retrieval technique. Three cases were immunoreactive with CAM5.2
      and eight cases were immunoreactive with EMA. All control cases lacked
      immunoreactivity with the cytokeratin panel and EMA. The spindle cells in the
      metaplastic breast tumours (88%) and in the controls (97%) stained with vimentin.
      CONCLUSIONS: Wide spectrum screening keratin may be the most useful and
      convenient antibody in differentiating metaplastic spindle cell carcinoma from
      other spindle cell lesions in the breast.

PMID- 12047769
TI  - p53 expression related to the aggressive infiltrative histopathological feature
      of basal cell carcinoma.
AB  - AIMS: To determine whether the p53 protein expression which is involved in the
      genesis and progression of various malignant tumours may relate to age, sites or
      the aggressive histopathological feature of the basal cell carcinoma. METHODS ADN
      RESULTS: One hundred and fifty-eight basal cell carcinoma specimens from
      Songklanakarind Hospital, southern Thailand, collected from January 1992 to
      December 2000, were examined by immunohistochemistry using polyclonal anti-p53
      CM1 (Novocastra Laboratories, Newcastle, UK; dilution 1:700). p53 protein
      expression was demonstrated in 48.7% of cases. The multivariate analysis showed
      that the aggressive infiltrative histopathological type was significantly
      associated with p53 expression (odds ratio 2.95, 95% confidence interval 1.10
      7.90), whereas age, sun-exposure site, cellular response and fibrosis were not.
      CONCLUSIONS: The p53 expression is found to be related to the aggressive
      histopathological feature, which may be of predictive value for the behaviour of
      basal cell carcinoma. However, this result does not support the relation between
      sun exposure inducing basal cell carcinoma and p53 protein expression.

PMID- 12047772
TI  - Myxoglobulosis-like change in a lower lip mucocele.

PMID- 12047773
TI  - Osteoblastic differentiation from atypical myoepithelial cells.

PMID- 12047774
TI  - Lymphoid-associated neoplasia in herniated colonic mucosa.

PMID- 12047775
TI  - Granulomas in hepatocellular carcinoma induced by lipiodolized SMANCS, a polymer
      conjugated derivative of neocarzinostatin.

PMID- 12047776
TI  - The myocardial performance index in patients with aortic stenosis.
AB  - OBJECTIVES: This study was designed to determine the effect of chronic afterload
      on a Doppler-derived myocardial performance index (MPI) combining both systolic
      and diastolic left ventricular dysfunction. METHODS: The study included 36
      patients with a diagnosis of aortic stenosis and 36 normal subjects. Doppler
      derived myocardial performance index (MPI), defined as the sum of the isovolumic
      contraction time and isovolumic relaxation time divided by ejection time, was
      measured from the mitral valve inflow and left ventricular outflow velocity
      patterns and was then related to the aortic valve area, valve gradient, and other
      echocardiographic variables. RESULTS: The values of the Doppler-derived MPI in
      the patients with aortic stenosis were significantly higher than those in the
      controls (0.54 +/- 0.20 vs 0.38 +/- 0.04, respectively; P < 0.001). Transmitral
      deceleration time and the E/A ratio ( r = 0.47 and r = 0.35, respectively; P <
      0.05) were significant univariate correlates, and mitral deceleration time was
      the only significant correlate of MPI. However the index did not correlate with
      aortic valve area, peak and mean valve gradients, left ventricular mass, or age.
      CONCLUSIONS: Doppler-derived MPI reflects severity of global left ventricular
      dysfunction in patients with aortic stenosis and may be of clinical value in this
      patient population.

PMID- 12047777
TI  - Importance of the index of myocardial performance in evaluation of left
      ventricular function.
AB  - The index of myocardial performance (MPI) has been used as an easily obtainable
      parameter that reflects both systolic and diastolic functions of the myocardium
      and correlates closely with invasive measurements. This study investigated the
      importance of MPI on assessment of left ventricular function in patients with
      critical coronary artery disease. METHODS: We studied 82 patients who had
      coronary angiography and echocardiography. Patients in Group A were without
      critical coronary stenosis (n = 37, 17 females, 20 males, mean age 54 +/- 11
      years) and patients in Group B had critical coronary stenosis (> 70%) without
      previous myocardial infarction (n = 45, 18 female, 27 male, mean age 57 +/- 10
      years). Using echocardiographic parameters, left ventricular isovolumetric
      relaxation time (IRT), isovolumetric contraction time (ICT), ejection time (ET),
      ratio of velocity time integrals (vti) of early and late diastolic mitral flow
      (E/Avti), E deceleration time (EDT), MPI [(IRT + ICT) / ET], ejection fraction
      (EF), and fractional shortening (FS) were calculated. During cardiac
      catheterization, Dp/Dt [(diastolic blood pressure - left ventricular end
      diastolic pressure) / ICT] was calculated. RESULTS: There were significant
      differences in IRT, EDT, E/Avti, and the MPI between Groups A and B (95.9 +/-
      14.7 and 113.4 +/- 14.3 msec, P < 0.001; 164.5 +/- 44.8 and 186.2 +/- 33.6 msec,
      P < 0.05; 1.51 +/- 0.45 and 1.24 +/- 0.80 msec, P < 0.05; and 0.45 +/- 0.08 and
      0.53 +/- 0.07 msec, P < 0.001, respectively), but there were no significant
      differences in ICT, ET, EF, FS, and Dp/Dt between the two groups. Both groups
      showed a close correlation between MPI and Dp/Dt (r = - 0.78 for Group A and r = 
      0.82 for Group B). There were no significant differences in heart rate and
      systolic and diastolic blood pressure between the two groups. CONCLUSION: These
      data suggest that MPI may be a useful parameter and an early indicator of left
      ventricular dysfunction in patients with critical coronary artery disease and
      normal systolic function.

PMID- 12047779
TI  - Ventricular interdependence in patients with dual-chamber pacing: a Doppler
      tissue imaging study.
AB  - PURPOSE: To analyze pulsed-Doppler tissue imaging (DTI) of the right ventricular
      (RV) tricuspid annulus and left ventricular (LV) mitral annulus in patients paced
      in the DDD mode at three different pacing modes as compared with healthy
      subjects, and to investigate possible physiologic interaction between the RV and
      LV in this subgroup of patients. METHODS: We selected a population of 22 subjects
      with pacemakers (PM) for atrioventricular (AV) block and/or sick sinus syndrome
      and compared them to 20 healthy subjects. Standard echo Doppler and DTI
      parameters were measured at baseline (heart rate [HR] 70 beats/min; AV delay 125
      msec) and after at least 5 minutes of constant stimulation at two different
      pacing modes: (1) HR 70 beats/min, AV delay 188 msec, and (2) HR 89 beats/min, AV
      delay 125 msec. LV stroke volume was obtained by LV outflow Doppler method.
      RESULTS: In the PM group, RV and LV annulus exhibited significantly higher peak
      systolic (S(m)) and early (E(m)) diastolic wall velocities than controls. In the
      PM population, LV stroke volume was strongly associated to RV E(m) peak velocity
      (r = 0.83; P < 0.00001) and RV S(m) peak velocity (r = 0.81; P < 0.0001). These
      associations between LV stroke volume and RV DTI parameters remained significant
      even after increase of HR and AV delay in the pacing modalities. Moreover,
      univariate relations were found in the PM group between DTI indexes of RV
      tricuspid annulus and the homologous indexes of LV mitral annulus. In a multiple
      linear regression analysis, both RV E(m) (P < 0.001) and RV S(m) (P < 0.001) were
      related independently to LV stroke volume (cumulative R(2) = 0.85, P < 0.00001).
      CONCLUSIONS: Our findings suggest the usefulness of pulsed-DTI to display
      physiologic ventricular interaction in patients with PM. Therefore, DTI may be
      taken into account as a valuable supporting tool to predict LV systolic
      performance and to select the most appropriate pacing mode in individual PM
      patients.

PMID- 12047778
TI  - Use of cyclic variation of integrated backscatter to assess contractile reserve
      and myocardial viability in chronic ischemic left ventricular dysfunction.
AB  - The detection of viable myocardium has important implications for management, but
      use of stress echocardiography to detect this is subjective and requires exposure
      to dobutamine. We investigated whether cyclic variation (CV) of integrated
      backscatter (IB) from the apical views could provide a resting study for
      detection of contractile reserve (CR) and prediction of myocardial viability in
      27 patients with chronic ischemic left ventricular (LV) dysfunction. Repeat
      echocardiography was performed after 6.7 +/- 3.8 months of follow-up; 14 patients
      underwent revascularization and 13 were treated medically. Using a standardized
      dobutamine echocardiography (DbE) protocol, images from three apical views were
      acquired at 80-120 frames/sec at rest and during stress. CR was identified if
      improvement of wall motion was observed at low dose (5 or 10 microg/kg/min) DbE.
      Myocardial viability was characterized by improvement at follow-up
      echocardiography in patients with revascularization. CVIB at rest and low dose
      dobutamine were assessed in 194 segments with resting asynergy (severe
      hypokinesis or akinesis), of which 88 (45%) were in patients who underwent
      revascularization. Of these, CVIB could be measured in 190 (98%) segments at rest
      and 185 (95%) at low dose dobutamine. Sixty-two (33%) segments had CR during low
      dose DbE and 50 (57%) segments showed wall-motion recovery (myocardial viability)
      at follow-up echocardiography. Segments with CR had significantly higher CVIB at
      rest (P < 0.001) and low dose dobutamine (P = 0.005) than segments without CR.
      Using optimal thresholds of CVIB (> 8.2 dB) at rest, the accuracy of CVIB for
      detecting CR was 70%. Compared with nonviable segments, viable segments had
      significantly higher CVIB at rest (P < 0.001) and low dose dobutamine (P <
      0.001). Using optimal thresholds of CVIB (> 5.3 dB) at rest, the accuracy of CVIB
      for detecting myocardial viability was 85%, which was higher than that in
      conventional DbE (62%, P < 0.01). Thus, assessment of CVIB from the apical views
      is a feasible and accurate tool for detecting CR and predicting myocardial
      viability in chronic LV dysfunction.

PMID- 12047780
TI  - Feasibility of pulsed-Doppler tissue imaging of the interventricular septum
      during exercise echocardiography.
AB  - BACKGROUND: A limitation of exercise echocardiography (EE) is its
      semiquantitative approach in analyzing wall-motion abnormalities. However, pulsed
      Doppler tissue imaging is capable of a systolic and diastolic regional
      quantitative assessment. METHODS: To investigate the feasibility of performing
      pulsed-Doppler tissue imaging sampling of the basal left ventricular (LV) septum
      during EE, we studied 105 consecutive patients (71 men, 34 women, aged 61 +/- 11
      years). Harmonic two-dimensional (2-D) echocardiography was performed at rest and
      peak EE, whereas pulsed-Doppler tissue imaging was performed at rest and
      immediately after EE. Adequate recordings for peak systolic velocity (Vs) were
      possible in all patients, but peak early diastolic (Ve) and peak late diastolic
      (Va) velocities were possible in 78 (74%) patients. Positive 2-D echocardiography
      was considered as infarction or an ischemic response. RESULTS: Forty-five (43%)
      patients (Group 1) had wall-motion abnormalities involving the left anterior
      descending artery (LAD) territory (29 with ischemia, 11 with ischemia and
      necrosis, and 5 with necrosis), 21 (20%) (Group 2a) had wall-motion abnormalities
      involving the left circumflex (LCX) and/or the right coronary artery (RCA)
      territories, and 39 (37%) (Group 2b) had normal EE. Heart rate increased from 72
      +/- 17 beats/min to 143 +/- 18 beats/min (P < 0.0001) and systolic blood pressure
      from 129 +/- 19 mmHg to 174 +/- 26 mmHg (P < 0.001). Coronary angiography was
      performed in 30 (29%) patients, 29 of whom had positive findings on EE. LAD or
      diagonal branch coronary artery disease (CAD) (> or = 50% luminal narrowing) was
      present in 22 patients, 10 of whom had proximal severe stenosis (> or = 70%
      luminal narrowing). Vs increase was significatively lower in Group 1 (40 +/- 35%,
      from 6.0 +/- 1.5 cm/sec to 8.1 +/- 2.2 cm/sec) than Group 2a (75 +/- 35%, from
      6.3 +/- 1.4 cm/sec to 10.8 +/- 2.1 cm/sec, P < 0.0001) and Group 2b (64 +/- 27%,
      from 6.7 +/- 1.3 cm/sec to 10.9 +/- 2.0 cm/sec, P < 0.001). Ve was not different
      at rest and at postexercise between groups. Va was similar at rest but higher at
      postexercise in Group 2b than Group 1 (11.8 +/- 2.3 cm/sec vs 10.3 +/- 3.0
      cm/sec, P < 0.05). Failure to achieve Vs > or = 9.5 cm/sec after exercise was
      found to be the more accurate limit to detect necrosis or ischemia in the LAD
      territory according to EE criteria (sensitivity 76%, specificity 78%). When
      analysis was limited to the 30 patients who underwent angiography, we found that
      the 10 patients with proximal severe LAD or diagonal branch stenosis showed
      blunted increases in Vs (increase 9.4 +/- 19%, from 6.5 +/- 1.2 cm/sec at rest to
      7.4 +/- 1.7 cm/sec at post-EE; P = 0.17) in contrast to the 20 patients having
      moderate or nonsignificant stenosis (increase 31 +/- 20%, from 6.2 +/- 1.5 cm/sec
      at rest to 9.3 +/- 1.8 cm/sec at post-EE, P < 0.0001). A failure to increase Vs >
      or = 30% had a sensitivity of 90% and a specificity of 80% in detecting proximal
      severe stenosis. CONCLUSION: Pulsed-Doppler tissue imaging sampling of the LV
      septum is feasible technically during EE and allows quantification of the
      regional response. This method may be accurate for detecting proximal severe
      stenosis in vessels supplying the LAD territory.

PMID- 12047781
TI  - Prognostic value of dobutamine echocardiography in elderly patients with
      suspected coronary artery disease and an abnormal resting electrocardiogram.
AB  - The prognostic value of dobutamine stress echocardiography (DE) in elderly
      patients over 70 years of age with suspected coronary artery disease (CAD) and an
      abnormal electrocardiogram (ECG) at rest has not been well documented. We
      investigated 158 consecutive outpatients (97 men) aged 76 +/- 4 years presenting
      with right bundle branch block with or without a left anterior hemiblock (41%),
      left bundle branch block (23%), or repolarization abnormalities (36%). The basic
      clinical and echocardiographic data were analyzed and correlated with the DE
      results. The patients were followed for a mean of 24 +/- 13 months. Twenty-three
      (14.5%) patients presented with a nonfatal cardiac event (CE). According to
      univariate analysis, the parameters associated with the onset of a CE included
      arterial hypertension, angina pectoris, anti-angina therapy, the presence of
      calcifications on the aortic valve and the ascending walls of the aorta, and the
      presence of segmental-contraction abnormalities of the left ventricle (LV) at
      rest during echocardiography. According to a Cox regression model, the only
      independent predictive parameter for the onset of a CE was the appearance of
      segmental-contraction abnormalities of the LV and their severity during peak dose
      administration during DE (odds ratio [OR] = 2.58, P < 0.001). This parameter
      remains independent when spontaneous CEs (myocardial infarction and unstable
      angina) were considered as endpoints (OR = 2.31, P < 0.001). CONCLUSIONS: DE is a
      safe and reliable method for investigating CAD in patients over 70 years of age
      with an abnormal resting ECG. In our study, the most predictive independent
      parameter for the onset of a CE was the appearance of segmental-contraction
      abnormalities of the LV and their severity during DE.

PMID- 12047782
TI  - Comparative prognostic significance of transesophageal versus transthoracic
      stress echocardiography.
AB  - Patients with a negative transthoracic stress echocardiographic study (TTE-SE)
      are at low risk for adverse cardiac events. Because of a higher sensitivity for
      detection of coronary artery disease, transesophageal dobutamine stress
      echocardiography (TEE-DSE) might permit identification of an even lower risk
      population. We compared the relative prognostic values of TTE-SE and TEE-DSE in
      236 patients with negative stress echocardiograms. Baseline and follow-up
      information on 236 consecutive subjects who had a negative stress
      echocardiographic study during the period of October 1996 to December 1997 was
      obtained. Baseline cardiac risk factors and major cardiac events (nonfatal
      myocardial infarct or cardiac death) were identified. Follow-up was obtained in
      233 subjects for a mean duration of 25 months. At baseline, the TEE-DSE group had
      more hypertensives (85% vs 67%, P = 0.02) and more baseline wall-motion
      abnormalities (41% vs 26%, P = 0.03). At 34 months of follow-up, there was no
      significant difference in the occurrence of major cardiac events between the two
      groups (8% vs 8.6%, P = NS). In the TEE-DSE group, there were more than twice as
      many events in the second year of follow-up as compared with the first year,
      indicating that a negative TEE-DSE has lessened prognostic value 1 year after the
      test. Standard TTE-SE provides prognostic data in patients at high risk for major
      cardiac ischemic events that is equivalent to that obtained by TEE-DSE. While
      advances in ultrasound techniques may improve our ability to detect coronary
      artery disease, it remains to be seen whether this will have an impact on
      prognostication.

PMID- 12047783
TI  - Prevalence and clinical significance of left atrial spontaneous echo contrast
      detected by transesophageal echocardiography.
AB  - The prevalence and clinical significance of left atrial spontaneous echo contrast
      (SEC) were studied in patients undergoing transesophageal echocardiography (TEE).
      The study group included 290 consecutive patients (186 male and 104 female, aged
      17-86 years, mean age 56.1 +/- 12.8 years). Left atrial SEC was found in 50
      (17.2%) patients, and was significantly associated with atrial fibrillation,
      mitral stenosis, absence of mitral regurgitation, and left atrial dimension.
      Atrial fibrillation was recorded in 44 (88%) patients, mitral stenosis or mitral
      valve replacement in 21 (42%) patients, and left atrial thrombus or previous
      embolism in 23 (46%) patients with SEC. Univariate analysis showed a significant
      association between the presence of SEC and atrial fibrillation, mitral stenosis
      or mitral valve replacement, and left atrial size. Multivariate analysis showed
      the presence of left atrial SEC and atrial fibrillation to be independent factors
      for thrombus formation and/or thromboembolism. Since left atrial SEC associated
      with atrial fibrillation, left atrial enlargement, mitral stenosis, or mitral
      valve prosthesis was found in 17.2% of patients undergoing TEE, it might be
      considered a marker of left atrial thrombus or previous thromboembolism.

PMID- 12047784
TI  - Continuous ultrasonic monitoring of balloon valvuloplasty.
AB  - A novel ultrasound transducer developed in our laboratory (CONTISON) was used for
      monitoring catheter balloon commissurotomy (CBC). The transducer was placed at
      the cardiac apex to obtain an apical four-chamber view and attached to the chest
      wall using an adhesive ring. During the procedure, the tip of the needle was
      imaged first in the right atrium and was seen to traverse the interatrial septum
      and enter the left atrium. Mitral valve gradients were measured before and after
      CBC.

PMID- 12047785
TI  - Constrictive pericarditis localized to left ventricle presented with left pleural
      effusion: a case report.
AB  - An 18-year old woman presented with progressive dyspnea and cough. Physical
      examination revealed decreased breath sounds at the left hemithorax and distant
      heart sounds with no murmurs or rub. Electrocardiogram revealed low voltage.
      Chest X-ray showed unilateral left-sided pleural effusion with no cardiomegaly.
      Transthoracic echocardiogram showed thickened pericardium localized throughout
      the left ventricle impairing the diastolic filling. Doppler waveforms were
      suggestive of localized constrictive pericarditis. A computerized tomographic
      scan of the chest confirmed the presence of unilateral pleural effusion with
      thickened pericardium surrounding the left ventricle. The patient's symptoms and
      signs were related to localized constrictive pericarditis and improved following
      surgery.

PMID- 12047786
TI  - Cardiac echinococcosis causing acute dissection of the left ventricular free
      wall.
AB  - Cardiac echinococcosis is a rare condition, and its manifestations are protean
      depending upon its site of infestation. We report a case of hydatid heart disease
      presenting like an acute cardiac ischemic episode associated with a rise in serum
      cardiac enzymes secondary to left ventricular free wall dissection caused by
      ruptured intramyocardial echinococcal cyst. The resultant complex cardiac anatomy
      was characterized fully by echocardiographic examination.

PMID- 12047787
TI  - Three-dimensional reconstruction of heart defects associated with Williams-Beurer
      syndrome.
AB  - Williams-Beurer syndrome is an unusual genetic alteration associated with
      congenital heart defects. We present the capabilities of three-dimensional
      echocardiography in the study of the cardiopathy associated with this syndrome.

PMID- 12047789
TI  - Transesophageal contrast echocardiography distinguishes a left atrial appendage
      thrombus from spontaneous echo contrast.

PMID- 12047788
TI  - Is it open or is it closed? Thrombosis of a St. Jude's tricuspid valve
      prosthesis.
AB  - A 49-year-old woman with mitral and tricuspid mechanical valve prostheses
      developed marked weight gain with increasing abdominal girth and facial plethora
      4 weeks after anticoagulation was temporarily interrupted for abdominal surgery.
      Transthoracic and transesophageal echocardiography documented severe tricuspid
      stenosis and regurgitation. The two discs of the tricuspid prosthesis were
      immobilized, half open and half closed. The prosthesis was replaced and the
      patient did well.

PMID- 12047790
TI  - Transesophageal two- and three-dimensional echocardiographic diagnosis of
      combined left ventricular pseudoaneurysm and ventricular septal rupture.
AB  - Two- (2-D) and three-dimensional (3-D) transesophageal echocardiography (TEE)
      were useful in making the diagnosis of combined left ventricular pseudoaneurysm
      and ventricular septal rupture in an elderly patient presenting with
      mediastinitis and worsening heart failure following coronary artery bypass graft
      surgery. The diagnosis was not suspected clinically. Three-dimensional TEE served
      to increase the confidence level with which the diagnosis of this combined lesion
      was made. Additionally, 3-D TEE proved superior to 2-D TEE in assessing the size
      of the left ventricular rupture site.

PMID- 12047791
TI  - Clinical management of the obese hypertensive patient.
AB  - Despite years of investigation our fundamental and clinical knowledge of the
      major public health problem, obesity-hypertension, is relatively meager and
      certainly inadequate. We are at a loss to explain why the pathophysiological
      mechanisms of obesity and hypertension are so inextricably intertwined. Adding to
      this frustration is the inadequacy of the treatment for obesity. Hemodynamically,
      we recognize that the expanded plasma volume caused by obesity imparts a
      significant volume overload on the heart, thereby increasing cardiac output,
      while the hypertension compounds this ventricular stress by an associated
      pressure overload. Thus, the ventricle has an eccentric as well as a concentric
      adaptive hypertrophy. Associated with obesity is an increased burden of pressor
      (e.g., catecholamine, angiotensin II); peptide (e.g., endothelin, insulin,
      leptin, natriuretic); hormonal (e.g., growth, steroids, thyroid); and neural
      mechanisms. Further complicating these alterations are electrolytic, lipid, uric
      acid, and other metabolic factors. Both diseases (obesity and hypertension) are
      exacerbated by frequently encountered comorbid pathophysiological disorders
      including atherosclerosis, ventricular dysfunction, diabetes mellitus,
      hyperlipidemias, and sleep apnea. To add to these issues, therapy for obesity
      hypertension is suboptimal. Behavioral modification (of overweight and obesity)
      is commonly characterized by recidivism, and pharmacotherapy of obesity is
      woefully inadequate; the present agents either raise arterial pressure or are
      fraught with adverse effects. Fortunately, there are no contraindications
      imparted by obesity that complicate the drug treatment of the associated
      hypertension. Each of the lifestyle modifications and seven classes of
      antihypertensive therapy that is discussed herein is done in light of the
      coexistent hypertension and comorbid diseases.

PMID- 12047792
TI  - Interventions for aortic coarctation.
AB  - The standard treatment of coarctation of the aorta is surgical. In the last 2
      decades, however, treatment by catheter intervention has become more widespread,
      using either balloon angioplasty or primary stent implantation. Balloon
      angioplasty was originally used for recurrent coarctation after surgical repair
      but has now been shown equally effective for unoperated coarctation. The
      procedure produces a satisfactory gradient reduction in approximately 80% of
      patients, with transverse arch hypoplasia the main predictor of poorer outcome.
      Rates of restenosis and aneurysm formation are less than 10%. Primary stent
      implantation has been suggested as an option potentially superior to angioplasty
      alone. Stent implantation limits elastic recoil and potentially reduces aneurysm
      formation by reducing the amount of balloon stretch required. The incidence of
      suboptimal gradient reduction is low, probably 5% or less, as is the rate of
      restenosis. Aneurysm formation, vascular complications, and stent migration also
      occur in less than 5%. Catheter interventions are now an established treatment
      strategy for coarctation, with a good success rate and safety profile. The
      outcome for native and recurrent coarctation appears similar. The authors believe
      that for most adult patients with coarctation of the aorta, catheter intervention
      should be offered as initial therapy.

PMID- 12047793
TI  - Cardiac imaging in women: use of radionuclide myocardial perfusion imaging and
      echocardiography for acute chest pain.
AB  - Evidence for the value of noninvasive cardiac imaging in patients for the
      detection of ischemic heart disease has traditionally come from trials using male
      patients. The application of such technology for women is often presumptive.
      Because there is an overall lower prevalence of ischemic heart disease in women,
      difference in body habitus, and smaller heart size, cardiac imaging in women
      presents unique challenges for imaging specialists and cardiologists. With the
      introduction of technetium-99 meters perfusion agents, gated single-photon
      emission computed tomography, and attenuation correction, myocardial perfusion
      imaging (MPI) in women has achieved a high sensitivity and specificity for the
      detection of coronary artery disease similar to that observed in men. With
      harmonic imaging and myocardial contrast agents, two-dimensional echocardiography
      offers comparable diagnostic accuracy in women. More importantly, MPI and stress
      echocardiography have prognostic value in predicting future cardiovascular
      events. The severity and extent of the single-photon emission computed tomography
      myocardial perfusion defects independently predict future cardiovascular events.
      Myocardial perfusion rest imaging during acute chest pain has a 99% negative
      predictive value of subsequent cardiovascular events, and a positive study MPI is
      the most important predictor for future cardiac events. Both MPI and stress
      echocardiography can direct high-risk patients to more invasive management or
      selectively identify lower-risk patients, allowing safe discharge from the
      emergency department and unnecessary hospitalization. Using a triage approach
      incorporating MPI or rest echocardiography in patients with acute chest pain
      results in significant cost savings. However, data on rest imaging in women
      during acute chest pain are still lacking.

PMID- 12047794
TI  - Hypertriglyceridemia: a review beyond low-density lipoprotein.
AB  - Hypertriglyceridemia is made up of a complex array of dyslipidemias. Difficulties
      in establishing the independent predictive value of elevated triglycerides in
      coronary artery disease arise because the triglyceride-rich lipoprotein particles
      that accumulate are diverse, with differential atherogenic potential, and because
      hypertriglyceridemia states are typically associated with low high-density
      lipoprotein cholesterol. When high-density lipoprotein cholesterol is considered
      in multivariate analysis of the role of hypertriglyceridemia in coronary artery
      disease, the importance of elevated triglycerides pales, emerging as a
      statistical second fiddle. However, recent data have affirmed the primary role of
      triglycerides in the genesis of atherosclerosis. This process involves the
      overabundance of triglyceride-rich lipoprotein particles, which, paradoxically,
      can be enriched with cholesterol through the action of cholesterol ester transfer
      protein. These particles appear to be especially atherogenic. Also, low-density
      lipoproteins become smaller and denser-small, dense phenotype or pattern B-in
      hypertriglyceridemia states. This profile is associated with a threefold increase
      in coronary artery disease risk and is not evident on routine lipid testing.
      Aggressive management of hypertriglyceridemia requires more detailed lipid
      analyses to identify patients at risk. In treating hypertriglyceridemia, a risk
      factor beyond low-density lipoprotein would allow a broader definition of
      patients at risk for coronary artery disease so that more people would benefit
      from lipid-lowering initiatives.

PMID- 12047795
TI  - Risk stratification and prevention of sudden death in hypertrophic
      cardiomyopathy.
AB  - Sudden unexpected death, often occurring in young, asymptomatic patients, is the
      most devastating facet of the natural history of hypertrophic cardiomyopathy, and
      appears to be the consequence of primary ventricular tachyarrhythmias arising in
      an electrically unstable myocardial substrate characterized by disorganized
      cellular architecture, ischemia, cell death, and replacement scarring. Although
      precise identification of all hypertrophic cardiomyopathy patients at high risk
      for a catastrophic event is a clinical challenge, effective treatment strategies
      for the prevention of sudden death with the implantable cardioverter
      defibrillator are now available.

PMID- 12047796
TI  - Mechanical or metabolic treatment for coronary disease: synergistic, not
      antagonistic, approaches.
AB  - Cardiologists have traditionally focused on coronary narrowing as seen on
      angiography and have orientated treatment towards bypassing these lesions or
      widening them with angioplasty. In patients with stable coronary artery disease,
      percutaneous coronary interventions reliably relieve angina and myocardial
      ischemia, but do not prevent myocardial infarction or reduce mortality.
      Cholesterol lowering therapy has been shown, in several large, randomized trials
      reported over the past decade, to reduce mortality and coronary events, including
      the need for revascularization in a broad spectrum of patients. Mechanical and
      metabolic treatments for coronary disease should be used synergistically.

PMID- 12047797
TI  - High-output congestive failure in a patient with pulmonary arteriovenous
      malformations.
AB  - Pulmonary arteriovenous malformations are rare vascular malformations that
      usually present with dyspnea and cyanosis in young adults. With the exception of
      infants and newborns, pulmonary arteriovenous malformations rarely cause
      congestive heart failure. The authors describe an unusual case in which an
      elderly female presented with severe dyspnea, hypoxemia, and high-output heart
      failure. Spiral CT of the chest and pulmonary angiography revealed three large,
      lower-lobe arteriovenous malformations that were successfully embolized, leading
      to resolution of her hypoxemia and symptoms.

PMID- 12047798
TI  - Squirrel monkeys and space motion sickness.
AB  - Studies of the vestibular system in squirrel monkeys in consideration of space
      motion sickness (SMS) or space adaptation syndrome (SAS) were reviewed. First,
      the phylogenetic position of the squirrel monkey was considered. Then the
      anatomico-physiological studies of both the peripheral and the central vestibular
      systems were described, because the vestibular system is crucially important in
      the genesis of SMS (SAS). In this connection, the ablation studies of labyrinth,
      semicircular canals, and other SAS-related areas were referred to, and
      consideration was made for experiments about caloric irrigation of the ear. A
      hypothetic model was then proposed for the genesis of SAS.

PMID- 12047799
TI  - Estimation of baroreflex gain using a baroreflex equilibrium diagram.
AB  - Two types of closed-loop perturbations can be applied to the arterial baroreflex
      system. The first (P(D1)) is introduced into the baroreceptors without a direct
      effect on arterial pressure (AP), whereas the second (P(D2)) initially affects
      AP. Neck suction and hemorrhage are examples of P(D1) and P(D2), respectively. To
      estimate the baroreflex open-loop gain (G(Baro)) without knowing the absolute
      magnitudes of P(D1) and P(D2), we explored a new strategy to estimate G(Baro) by
      combining P(D1) and P(D2) in a baroreflex equilibrium diagram. In this diagram,
      the neural arc presents the input-output relationship between baroreceptor
      pressure input and sympathetic nerve activity (SNA). The peripheral arc presents
      the input-output relationship between SNA and AP. In 8 anesthetized rabbits, we
      estimated G(Baro) by multiplying the slopes of the peripheral arc determined from
      P(D1) and the neural arc determined from P(D2). We also estimated G(Baro) by a
      conventional open-loop analysis. The G(Baro) values estimated by the equilibrium
      diagram and the open-loop analysis showed a positive correlation (y = 0.80x +
      0.22, r(2) = 0.95) and a standard error of estimate of 0.21 across the animals.
      We conclude that G(Baro) was estimated well by combining P(D1) and P(D2) in the
      equilibrium diagram.

PMID- 12047800
TI  - Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating
      delayed rectifier K(+) current.
AB  - Cell swelling enhances a slowly activating delayed rectifier K(+) current (I(Ks))
      in cardiac cells. This investigation was undertaken to determine which of the two
      structural units reconstituting the I(Ks) channel, KCNQ1 (KvLQT1) and KCNE1
      (minK/IsK), plays a key role in the cell swelling-induced I(Ks) enhancement and
      to dissect a possible involvement of tyrosine phosphorylation therein. KCNQ1 was
      transiently expressed alone or together with KCNE1 in a heterologous mammalian
      cell line. Two distinct whole-cell membrane currents were separately observed
      during the exposure of transfected cells to various degrees of hyposmotic
      solutions. A hyposmotic challenge (0.7 times control osmolarity) resulted in
      about a twofold increase not only in the heteromeric KCNQ1/KCNE1, but also in the
      homomeric KCNQ1 channel currents. There was no significant difference in the
      incremental ratio of current amplitude in response to hyposmotic stress between
      the two KCNQ1-related currents, and the cells expressing the heteromeric channels
      swelled less than those with the homomeric channels or without the exogenous
      ones. The cell swelling-induced I(Ks) enhancement was not affected by a protein
      tyrosine kinase (PTK) inhibitor, by genistein (50 microM), or by an inhibitor of
      phosphotyrosine phosphatase (PTP), orthovanadate (500 microM), or a
      nonhydrolyzable ATP analogue, AMP-PNP (5 mM). Taken together, it is very likely
      that KCNQ1 might primarily participate in the I(Ks) enhancement by osmotic cell
      swelling. The obligatory dependence of the I(Ks) augmentation on PTK activity
      remained to be demonstrated, at least, in this expression system.

PMID- 12047801
TI  - Frequency distribution, variance, and moving average of left ventricular rhythm
      and contractility during atrial fibrillation in dog.
AB  - Mean levels of left ventricular rhythm and contractility averaged over arrhythmic
      beats would characterize the average cardiac performance during atrial
      fibrillation (AF). However, no consensus exists on the minimal number of beats
      for their reliable mean values. We analyzed their basic statistics to find out
      such a minimal beat number in canine hearts. We produced AF by electrically
      stimulating the atrium and measured left ventricular arrhythmic beat interval
      (RR) and peak isovolumic pressure (LVP). From these, we calculated instantaneous
      heart rate (HR = 60,000/RR), contractility (E(max) = LVP/isovolumic volume above
      unstressed volume), and beat interval ratio (RR1/RR2). We found that all their
      frequency distributions during AF were variably nonnormal with skewness and
      kurtosis. Their means +/- standard deviations alone cannot represent their
      nonnormal distributions. A 90% reduction of variances of E(max) and RR1/RR2
      required a moving average of 15 and 24, respectively, arrhythmic beats on the
      average, whereas that of RR and HR required 60 beats on the average. These
      results indicate that a statistical characterization of arrhythmic cardiodynamic
      variables facilitates better understanding of cardiac performance during AF.

PMID- 12047802
TI  - Reserved higher vagal tone under acute hypoxia in Tibetan adolescents with long
      term migration to sea level.
AB  - Tibetans are known as one of the largest and oldest high-altitude natives in the
      world and are among the best high-altitude-adapted ethnic groups. They exhibit
      greater vagal tone and less sympathetic stimulation than acclimatized lowlanders
      at high altitudes. Whether young native Tibetans who had spent long-term
      residence (more than 3 years) at sea level still reserved their unique autonomic
      characteristics was the main aim of this study. Heart rate variability (HRV) of
      10 native young Tibetan male students and 12 Han counterparts were measured at
      resting supine position at sea level and 1 h after ascent to 3,700 m in a
      hypobaric chamber (PO(2) = 13.4 kPa). At sea level, Tibetans showed lower heart
      rate (HR) and greater HRV. At 3,700 m, the increase of HR was greater in the Hans
      than in the Tibetans, and the HRV was significantly diminished in the Han group
      but not in the Tibetan group. The results suggested that Tibetans had a greater
      parasympathetic dominance over the heart at rest, and acute moderate (3,700 m)
      hypoxia did not influence their HRV significantly, but it did on the Han
      subjects. We concluded that the long-term residence of the Tibetans at sea level
      did not change their unique characteristics of the autonomic systems.

PMID- 12047803
TI  - Model for the regulation of Ca(2+) release from the sarcoplasmic reticulum in
      heart muscle.
AB  - To elucidate the essential features of Ca(2+) release from the terminal sac (TS)
      of the sarcoplasmic reticulum (SR) in heart muscle, a model for Ca(2+) release
      from the TS was constructed based on the mechanism of Ca(2+)-induced Ca(2+)
      release by assuming a small TS volume. For numerical computation, we divided the
      cytoplasm in a half sarcomere into 50 compartments, one end of which faced the TS
      and determined the open probability of the Ca(2+) release channel in the TS.
      Ca(2+) moves from compartment to compartment by simple diffusion and is taken up
      from each compartment by the tubular SR via Ca(2+)-ATPase. Simulation based on
      one-dimensional diffusion of Ca(2+) showed that TS Ca(2+) release is smoothly
      graded over a wide range of levels of Ca(2+) influx when the TS is moderately
      loaded with Ca(2+), and it occurs in an all-or-none manner when the TS is heavily
      loaded with Ca(2+). The graded TS Ca(2+) release was generated with both local
      and uniform Ca(2+) influx into the cytoplasm. The propagation of the Ca(2+) wave
      was simulated by the use of a model consisting of several longitudinally
      consecutive sarcomeres with TS heavily loaded with Ca(2+). Mechanical alternans,
      characterized by an alternation of small and large twitches, was also simulated
      by applying Ca(2+) influx at an appropriate interval during which Ca(2+) was
      replenished to the TS at a constant rate. Thus the present model reflects several
      important aspects of TS Ca(2+) release in heart muscle.

PMID- 12047805
TI  - Age-related influences of leg vein filling and emptying on blood volume
      redistribution and sympathetic reflex during lower body negative pressure in
      humans.
AB  - To test the hypothesis that leg vein filling and emptying functions could be
      impaired with advancing age, which would produce less blood volume redistribution
      toward the lower body and smaller sympathetic reflex response during mild
      gravitational stress, 9 young and 10 elderly healthy males were exposed to a
      lower body negative pressure (LBNP) of 15 mmHg. Venous occlusion plethysmography
      was used to determine the functions of the leg veins. We found that the baseline
      venous distensibility index (VDI) was lower (0.057 +/- 0.004 vs. 0.048 +/- 0.003
      ml x 100 ml(-1) x mmHg(-1), young vs. elderly; p < 0.05), and half-emptying time
      (T(1/2)) was shorter (1.6 +/- 0.1 vs. 1.3 +/- 0.1 s, young vs. elderly; p < 0.05)
      in the elderly. At 15 mmHg-LBNP, VDI was decreased and T(1/2) was shortened
      significantly in the young group, but only slightly in the elderly group. Neither
      blood pressure nor heart rate changed significantly in either group. The
      reduction in peripheral venous pressure, which was recorded from the left
      antecubital vein at the cubital fossa, was less in the elderly, indicating a
      smaller decrease in central blood volume during LBNP; however, the enhancement of
      muscle sympathetic nerve activity was nearly the same as that in the young. We
      conclude that leg vein filling and emptying functions are impaired in elderly
      people, producing less blood pooling in the legs and smaller reduction in
      peripheral venous pressure during LBNP; the maintained sympathetic reflex
      response might be attributable to the well-preserved baroreflex function control
      of sympathetic outflow to the muscle in the elderly.

PMID- 12047804
TI  - Age-related changes in vasomotor reflex control of calf venous capacitance
      response to lower body negative pressure in humans.
AB  - The present study was performed to test the hypothesis that calf venous
      capacitance would be reduced by mild gravitational stress through a vasomotor
      reflex in humans, and this response could be diminished with advancing age. Nine
      young (31 +/- 1 years, mean +/- SE) and 9 elderly (69 +/- 1 years) healthy males
      were exposed to a lower body negative pressure (LBNP) of 15 mmHg. Venous
      occlusion plethysmography was used to measure calf venous capacitance and calf
      blood flow. Muscle sympathetic nerve activity (MSNA) was recorded
      microneurographically from the tibial nerve along with cardiovascular variables.
      It was found that baseline MSNA was higher [21 +/- 4 (mean +/- SE) vs. 37 +/- 5
      bursts x min(-1), young vs. elderly; p < 0.05] and calf venous capacitance was
      lower (1.71 +/- 0.12 vs. 1.44 +/- 0.10, ml x 100 ml(-1), young vs. elderly; p <
      0.05) in the elderly group. At 15 mmHg-LBNP, heart rate and mean arterial
      pressure both remained unchanged, MSNA was enhanced, and calf blood flow was
      reduced in all subjects. Calf venous capacitance during LBNP decreased in the
      young, but did not change in the elderly. A significant negative correlation
      between percent changes in MSNA and percent changes in calf venous capacitance
      existed in the young group (y = 20.171x-11.863, r = 20.682; p = 0.0432), but
      disappeared in the elderly group. The ratio of percent changes in calf venous
      capacitance to percent changes in MSNA was markedly lower in the elderly (p <
      0.01). In conclusion, these results substantiate our hypothesis that calf venous
      capacitance is reduced by mild LBNP through the vasomotor reflex, and this
      response is diminished in the elderly.

PMID- 12047806
TI  - Effects of long-term cold exposure on contractile muscles of rats.
AB  - The effects of 20-week cold exposure on contractile properties of soleus and
      extensor digitorum longus (EDL) muscles and plasma hormone levels were studied in
      rats. Twenty male Wistar rats (5 week old) were randomly divided into 2 groups (n
      = 10 each): cage-control and cold-exposed. The rats in the cold-exposed group
      were immersed in shoulder-deep water (approximately 18 degrees C) for 1 h/d, 5
      d/week, for 20 weeks. The temperature and humidity of the animal room with 12:12
      h light-dark cycle were maintained at approximately 23 degrees C and 55%,
      respectively. The rats were pair-fed powdered diets. The electromyogram
      activities in soleus and EDL were elevated by cold exposure. The body weight and
      absolute soleus wet weight of the cold-exposed group were significantly less than
      controls at the end of experiment. The one-half relaxation time and contraction
      time of EDL were significantly longer in the cold-exposed group than in the
      control group. The rate of twitch tension development, normalized by the maximum
      twitch tension, in EDL of the cold-exposed group was less than in the control
      group. Further, the fatigue resistance of EDL, but not of soleus, in response to
      train stimulation at 10 Hz was improved by cold exposure. The plasma levels of
      thyroid hormones, 3,5,3'-triiodothyronine and thyroxine, were significantly
      greater in cold-exposed group. Similar changes were also seen in the plasma
      catecholamine levels in the cold-exposed group (p > 0.05). It is suggested that
      long-term cold exposure causes a shift of the contractile properties of fast
      twitch EDL muscle toward the slow-twitch type. The results also indicated that
      the characteristics of muscles responded more strongly to an increased activity
      level than to the elevation of plasma hormones.

PMID- 12047807
TI  - Curvilinear VO(2):power output relationship in a ramp test in professional
      cyclists: possible association with blood hemoglobin concentration.
AB  - The purpose of this study was to determine (1) if there exists an additional,
      nonlinear increase (DeltaVO(2)) in the oxygen uptake observed (VO2 (obs)) at the
      maximal power output reached during a ramp cycle ergometer test and that expected
      (VO2 (exp)) from the linear relationship between VO(2) and power output below the
      lactate threshold (LT) in professional riders, and (2) the relationship between
      DeltaVO(2) and possible explanatory mechanisms. Each of 12 professional cyclists
      (25 +/- 1 years; VO(2 max): 71.3 +/- 1.2 ml x kg(-1) x min(-1)) performed a ramp
      test until exhaustion (power output increases of 25 W x min(-1)) during which
      several gas-exchange and blood variables were measured (including lactate,
      HCO(3)(-) and K(+)). VO(2) was linearly related to power output until the LT in
      all subjects. Afterward, a nonlinear deflection was observed in the VO(2):power
      output relationship (DeltaVO(2) = 2492 +/- 55 ml x min(-1) and p < 0.05 for VO2
      (obs) vs. VO2 (exp)). A significant negative correlation was encountered between
      DeltaVO(2) and resting hemoglobin levels before the tests (r = 20.61; p < 0.05).
      In conclusion, professional cyclists exhibit an attenuation of the VO(2) rise
      above the LT.

PMID- 12047808
TI  - Effects of head-down tilt on cerebral blood flow and somatosensory-evoked
      potentials in rabbits.
AB  - Changes in cerebral blood flow (CBF) and somatosensory-evoked potentials (SEPs)
      were studied in rabbits exposed to head-down tilt (HDT) at 45 degrees and 75
      degrees. The animals were anesthetized with alpha chloralose and the lungs were
      artificially ventilated. CBF was continuously measured by laser Doppler flowmetry
      (LDF), and SEPs were recorded as responses of the cortex to median nerve
      stimulation. In the 45 degrees HDT rabbits, CBF did not change significantly in
      the parietal cortex during 1 h of HDT. In contrast, in the 75 degrees HDT
      rabbits, CBF did not change significantly within 5 min after the onset of HDT,
      but decreased gradually to 79% of the pre-HDT baseline value at the end of 1 h of
      HDT. The latency and amplitude of SEPs did not change significantly throughout
      the experiment in any group. These results suggest that CBF and SEPs do not
      change significantly during 1 h of 45 degrees HDT and that 75 degrees HDT
      disturbs the regulation of the cerebral circulation but does not affect cortical
      somatosensory response, at least for 1 h.

PMID- 12047809
TI  - Effect of zinc-carnosine chelate compound on muscle function in mdx mouse.
AB  - The effect of antioxidant Z-103, catena-(S)-[mu-[N(alpha)-(3
      aminopropinyl)histidinnato-(2-)N(1),N(2),O:N(tau)]-zinc], on muscle function in
      the muscular dystrophy (mdx) mouse was examined by repetitive intraperitoneal
      administration in subjects aged 4 to 12 weeks. Z-103 administration at a dose of
      150 mg/kg increased the load resistant time (LRT), during which the animal with a
      load holds itself upright on a wire net. The Z-103 administration reduced
      hypertrophy, the ratio of centronucleated myofibers, and the rate of decay for
      magnitude of twitch force elicited by 0.5 Hz of electricity to the extensor
      digitorum longus (EDL) muscle of 12-week-old mdx mice, with little effect on the
      magnitude of twitch force. The administration of Z-103 (100 mg/kg) had a lesser
      effect on LRT and the other characteristics examined for EDL muscles. The
      constituent of Z-103, Zn(2+) applied in the form of ZnSO(4) (5 mg/kg), carnosine
      (100 mg/kg), and the combination of the two had no beneficial effect on mdx mice.
      Z-103 (150 mg/kg) administered to normal mice increased LRT with little effect on
      the contractile properties of EDL muscles. These results suggest that the
      administration of Z-103 ameliorates muscle function in the mdx mouse.

PMID- 12047811
TI  - Cellular signaling mechanisms underlying pharmacological action of Bak Foong
      Pills on gastrointestinal secretion.
AB  - Bak Foong Pills (BFP, also known as Bai Feng Wan) is an over-the-counter
      traditional Chinese medicine that has long been used for treating gynecological
      disorders and improving overall body functions, including gastrointestinal (GI)
      function. However, the cellular signaling mechanism underlying BFP action,
      especially on the GI tract, has not been elucidated. In the present study, the
      human colonic epithelia cell line T(84) was used as a model to investigate the
      effect of BFP ethanol extract on ion transport in conjunction with the short
      circuit current (I(SC)) technique. The results showed that the apical addition of
      BFP extract produced a concentration-dependent (10-1,000 microg/ml, EC(50) = 120
      microg/ml) increase in I(SC). The maximal response was observed at 500 microg/ml
      with an increase in I(SC) of 24.4 +/- 2.3 microA/cm(2) and apical conductance.
      The BFP-induced I(SC) was not observed when extracellular Cl(-) was replaced or
      when treated with Bumetanide (100 microM), an inhibitor of the Na(+)-K(+)-2Cl(-)
      cotransporter. The BFP-induced I(SC) was insensitive to the Na(+) channel
      blocker, amiloride, but partially inhibited by the Cl(-) channel blocker, DIDS
      (100 microM), and completely blocked by DPC (2 mM) or glibenclamide (1 mM) with a
      significant reduction in the apical conductance. The BFP-induced I(SC) could be
      mimicked by forskolin (10 microM), but inhibited by a pretreatment of the cells
      with adenylate cyclase inhibitor, MDL-12330A (10 microM). Pretreatment with EGTA
      (5 mM) and thapsigargin (10 microM) decreased the BFP-induced I(SC) by 10%. These
      results demonstrated that BFP ethanol extract exerted a stimulatory effect on
      gastrointestinal Cl(-) secretion by predominantly activating adenylate cyclase
      and apical cAMP-dependent Cl(-) channels, with minor contributions from calcium
      dependent Cl(-) channels. The effect of BFP may be explored to treat GI disorders
      such as constipation.

PMID- 12047810
TI  - Use of tetanus to investigate myofibrillar responsiveness to Ca(2+) in isolated
      mouse ventricular myocytes.
AB  - We used the relation between intracellular Ca(2+) concentration ([Ca(2+)](i)) and
      cell shortening during tetanus to evaluate the endogenous characteristics of
      Ca(2+) responsiveness of myofibrils in mouse ventricular myocytes. Enzymatically
      isolated myocytes were loaded with fura-2 AM (4 microM for 10 min), and the fura
      2 fluorescence ratio at 340 and 380 nm excitation wave length [F(340)/F(380)] and
      cell length were measured simultaneously. Following treatment with thapsigargin
      (0.2 microM) (an inhibitor of the Ca(2+) pump of sarcoplasmic reticulum),
      myocytes were stimulated at 10 Hz for 10 s to produce a tetanic contraction and
      an instantaneous plot of the fluorescence ratio signal versus cell length (R-L
      trajectory) was constructed. An increase in the extracellular Ca(2+)
      concentration ([Ca(2+)](o)) from 0.5 to 2 mM extended the R-L trajectory without
      a substantial shift of the relation. The R-L trajectory was shifted rightward by
      the nonselective phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xantine (IBMX,
      200 microM) (desensitization of the myofibrils to Ca(2+)), and shifted leftward
      by the Ca(2+) sensitizing thiadiazinone derivative, EMD-57033 (0.5 microM)
      (sensitization of the myofibrils to Ca(2+)). Beta-adrenergic stimulant,
      isoproterenol (5 nM), also shifted the R-L trajectory to the right, suggesting
      that the membrane receptor could be preserved. These results suggest that the R-L
      trajectory is a useful method to estimate the myofibrillar responsiveness to
      Ca(2+) in isolated mouse myocytes and can be applied to various mouse models of
      heart disease.

PMID- 12047814
TI  - Food security stakeholders in Hawaii: perceptions of food security monitoring.
AB  - OBJECTIVE: The purpose of this study was to document Hawai'i's food security
      stakeholders' perceptions of (1) definitions of food insecurity and hunger, (2)
      what should be measured, (3) how stakeholders interpret the Core Food Security
      Module (CFSM) and Face Valid Food Security Measure (FVFSM), and (4) the value of
      specific items in the CFSM. DESIGN: Perceptions were gathered through focus
      groups and interviews. SUBJECTS: The 43 stakeholders included 19 WIC
      nutritionists, 10 food pantry providers, 4 Hawaii foodbank board members, 4
      social workers, 3 legislators, and 3 homeless food providers. ANALYSIS PERFORMED:
      Transcripts were analyzed using constant comparative analysis of each question
      asked, comparisons between groups, and comparisons with the research literature.
      RESULTS: Stakeholders desired more detailed information than the CFSM currently
      yields and also a simple tool to measure the entire range of food insecurity that
      could be used to "help the needy." Participants favored the FVFSM over the CFSM
      because "it is more accurate as far as seeing the picture properly."
      IMPLICATIONS: A "Simple Food Security Monitoring Tool," which is based on the
      FVFSM, was created as an alternative tool for local food security monitoring.

PMID- 12047815
TI  - Preschool children's perceptions of food and their food experiences.
AB  - OBJECTIVE: Developmental theory suggests that children learn from their
      experiences. However, little is known about preschool children's interpretation
      of their daily food experiences. Therefore, the purpose of this research was to
      describe the criteria preschool children use to classify foods and their
      interpretation of their daily food experiences. DESIGN: Semistructured interviews
      and observations of children's play in toy kitchens were conducted with children
      enrolled in public preschool programs. SUBJECTS: Data were collected over a 2
      year period. During the first year of the study, observations and interviews were
      collected from 24 children. Interviews with an additional 79 children were
      conducted the following year. VARIABLES MEASURED: The variables measured included
      the children's criteria for food classification and their play behaviors in a toy
      kitchen. RESULTS: The children relied primarily on physical characteristics such
      as color, shape, and texture to classify foods. The activities that children
      demonstrated during play sessions included meal planning, food preparation, table
      preparation, serving food, eating, and cleaning. Pattern coding of the
      observational data revealed variability in (1) boys' and girls' kitchen play, (2)
      children's food selection and preparation methods and postmeal clean-up
      activities, and (3) children's responses to picky eating. IMPLICATIONS: These
      data may be used to develop a play-based nutrition education program.

PMID- 12047816
TI  - Perspectives of volunteers in emergency feeding programs on hunger, its causes,
      and solutions.
AB  - OBJECTIVE: To understand the social beliefs of volunteers in emergency feeding
      programs (EFPs) regarding hunger and whether volunteer experiences broadened
      understanding of hunger. DESIGN: An interpretivist paradigm and qualitative
      methods were used. SUBJECTS: Seventeen volunteers were recruited and interviewed
      from three EFPs. ANALYSIS: Interviews were analyzed using the constant
      comparative method. RESULTS: Volunteering in EFPs increased volunteers' awareness
      of the prevalence of hunger in their communities. More involved volunteers had a
      greater understanding of the life situations of the hungry. The volunteers felt
      that increasing self-sufficiency and private responses were appropriate solutions
      to hunger. The volunteers' attitudes and social beliefs were similar to those of
      the general public. IMPLICATIONS: Interventions that facilitate interaction
      between volunteers and clients, promote reflection on volunteer experiences, and
      provide alternative viewpoints on poverty are needed to broaden volunteers'
      understanding of hunger and food insecurity.

PMID- 12047817
TI  - Gender role preference and family food chores.
AB  - OBJECTIVE: To learn how couples stratified by gender role preference (GRP) manage
      food chores. DESIGN: One-time, individual semistructured qualitative interview
      with each partner in a couple representing 1 of 3 GRP pairings.
      SUBJECTS/SETTINGS: Volunteers were recruited using advertising and snowball
      sampling and met the criteria of (1) both parents living at home, (2) wife no
      older than 40, and (3) at least one child under age 6 and, if present, all others
      under age 18. Both partners in volunteer couples completed a 31-item GRP scale,
      and the scores of each partner were categorized as traditional (lowest 25% of
      possible scores), transitional (middle 50%), or egalitarian (top 25%). No
      traditional couples volunteered. A purposeful sample of 10 transitional and 10
      egalitarian wives representing 20 couples were interviewed. VARIABLES MEASURED:
      Each partner was asked to describe their current food chore responsibility, their
      opinion of the balance of responsibility, and how this role assignment had
      changed since first married. ANALYSIS METHODS USED: Thematic content analysis,
      constant comparison, and consensus produced the final thematic analysis. RESULTS:
      Couples in which both partners were transitional assigned food chore
      responsibility primarily to accommodate the breadwinner's role. Couples in which
      both partners were egalitarian used three different strategies to handle food
      chores. IMPLICATIONS: Educators should consider the differences found when
      designing interventions for recently married couples and parents of young
      children.

PMID- 12047818
TI  - The Team Nutrition pilot study: lessons learned from implementing a comprehensive
      school-based intervention.
AB  - Team Nutrition (TN) is an educational and promotional initiative developed by the
      US Department of Agriculture to change children's eating behaviors through social
      marketing techniques. This article reports on the process evaluation of a TN
      pilot project targeting students in kindergarten to grade 4 and systematically
      documents the implementation experience. Even with a very short start-up period,
      schools implemented most components of this multichannel nutrition intervention
      and formed new, supportive relationships with local media and community partners.
      School teachers and administrators, along with foodservice professionals,
      generally expressed support for and satisfaction with TN, citing the positive
      experience and gains for students. The lessons learned from this study highlight
      the management and organizational issues involved in a comprehensive
      intervention. These include the importance of local coordinators to support and
      create a bridge between teachers and cafeteria staff and to forge links with key
      external partners. To function effectively, coordinators themselves may need
      training in coalition building and working with media. Relationships formed with
      parents, local businesses, other educational institutions, health organizations,
      and the media offer promise for helping to sustain nutrition education efforts.
      The TN process evaluation identified multiple ideas for pursuing these
      partnerships more successfully.

PMID- 12047819
TI  - Nutrition jeopardy.

PMID- 12047820
TI  - Food safety for the pediatric population: the "Handle With Care" project.

PMID- 12047823
TI  - The nutrient and anthropometric status of physically active and inactive older
      adults.
AB  - OBJECTIVE: To assess nutrient intake, anthropometrics, and biochemical indicators
      in physically active and inactive older adults. DESIGN: A cross-sectional sample
      of older adults who participated in the Third National Health and Nutrition
      Examination Survey, 1988-94, was divided into two groups based on activity level.
      PARTICIPANTS/SETTING: A national sample of men (n = 1876) and women (n = 2009) 65
      years of age and older who reported diet and exercise information and were
      medically examined. MAIN OUTCOME MEASURES: Association of activity level with
      nutrients, anthropometrics, and biochemistries. ANALYSIS: Means were calculated
      for each of the variables observed by activity category. T tests were used to
      determine if the differences in the means were statistically significant at P
      <.05. RESULTS: Older adults reported intakes of food energy, calcium, magnesium,
      and zinc below recommendation. Nutrient intakes and anthropometrics for active
      and inactive women were similar; those for active and inactive men differed
      significantly for many nutrients and for anthropometrics associated with
      activity. CONCLUSIONS ANS IMPLICATIONS: Inadequate intakes of food energy and
      micronutrients are of concern because of the metabolic stresses associated with
      activity. Future research is needed to determine the impact of increased physical
      activity on nutrient needs and body composition in the elderly.

PMID- 12047824
TI  - Exercise as a gateway behavior for healthful eating among older adults: an
      exploratory study.
AB  - CONTEXT: The relationship between eating and exercise behavior change may
      influence effectiveness of interventions for older adults. OBJECTIVE: To
      determine whether exercise is a potential gateway behavior for healthful eating
      behavior among older adults. DESIGN: The Transtheoretical Model was applied to
      eating and exercise behaviors through the administration of a cross-sectional
      survey. SETTING/PARTICIPANTS: 205 older adults (the majority were white women)
      participating in congregate dining programs in a large Midwestern city. VARIABLES
      MEASURED: Perceived benefits and barriers, self-efficacy, and stage of change
      related to exercise and eating habits. ANALYSIS: Differences in responses to
      survey items based on stage of change were determined by analysis of variance, P
      <.05. RESULTS: Subjects in later stages for exercise behavior were also likely to
      be in later stages for eating adequate servings of fruit and dairy products but
      not for vegetables and avoiding fat. CONCLUSIONS AND IMPLICATIONS: Exercise is a
      potential gateway behavior for some dietary behaviors for older adults,
      justifying further controlled, longitudinal research.

PMID- 12047825
TI  - Use and reliability of the World Wide Web version of the Block Health Habits and
      History Questionnaire with older rural women.
AB  - OBJECTIVE: To estimate the parallel forms reliability of the paper and pencil and
      World Wide Web versions of the 1998 Block Health Habits and History Questionnaire
      (HHHQ) and to examine the feasibility of older women using the Web version.
      DESIGN: Within a 2-week period, participants completed both the paper and pencil
      and Web versions of the HHHQ and pre- and postsurveys about their comfort level
      and experience in using the computer. SUBJECTS: A convenience sample of 31 white
      women, aged 58.2 6.3 years, from a rural location were recruited via direct mail,
      public service announcements, and public posters. VARIABLES MEASURED: The
      parallel forms reliability of the HHHQ administered in two different ways and the
      perceptions of the women on their computer use were measured. ANALYSIS: Dietary
      data were analyzed using Pearson correlations and paired t tests. Alpha
      significance level was set at P <or=.05. RESULTS: The Web HHHQ had adequate
      reliability when compared with the paper and pencil version; paired sample
      correlations approximated acceptable coefficients (r >.70), with only vitamin C
      (r =.54) and iron (r =.65) falling below the acceptable standard. Eleven women
      indicated initial discomfort with the computer, but after the study, only three
      said they were uncomfortable completing the on-line survey. IMPLICATIONS:
      Internet dietary assessment tools could be a feasible assessment tool for older
      women to self-administer.

PMID- 12047826
TI  - Use of the Health Belief Model to examine older adults' food-handling behaviors.
AB  - OBJECTIVE: To measure the association among Health Belief Model (HBM) variables
      and safe food-handling behaviors among older adults. DESIGN: A mail survey using
      Dillman's Total Design Method. SETTING: In October 1999, a survey was sent to
      volunteers from a preexisting cohort of noninstitutionalized older adults living
      throughout Nevada. Data collection continued through January 2000. PARTICIPANTS:
      With a 56% response rate, the sample (n = 266) was composed mainly of women (73%)
      and individuals from urban counties (74%). The mean age was 68.09 years (SD =
      8.27). Except for gender, sample characteristics were similar to those of the
      preexisting cohort. VARIABLES MEASURED: Perceived threat of foodborne illness
      (ie, perceived severity and perceived susceptibility), cues to action (ie, media
      cues and educational cues), and safe food-handling behaviors (ie, sanitation and
      cross-contamination). ANALYSIS: Rank order correlation coefficients were computed
      to measure the association among variables. Significance was set at P <.05.
      RESULTS: Cues to action were positively related to perceived threat of foodborne
      illness and safe food-handling behaviors. Perceived severity of foodborne illness
      was positively related to one dimension of safe food-handling behaviors (ie,
      sanitation). CONCLUSIONS AND IMPLICATIONS: The HBM is a useful framework for
      examining food-handling behaviors among older adults.

PMID- 12047827
TI  - Overview of the diets of lower- and higher-income elderly and their food
      assistance options.
AB  - With the elderly becoming an ever-larger proportion of the American population,
      their dietary well-being is of increasing concern. In particular, lower-income
      elderly may face special challenges in maintaining a healthful diet. This group
      makes up a sizeable proportion of the elderly population; we estimate that almost
      1 in 5 (19%) of the elderly have household incomes at or below 130% of the
      federal poverty level, the income level that generally qualifies a household to
      participate in the federal Food Stamp Program. Here we examine the dietary
      intakes and related behaviors, as well as the food security status, of lower- and
      higher-income elderly and review major US government food and nutrition
      assistance programs that can be of benefit to the elderly, particularly those of
      low income. Our subjects are individuals 60 years of age and over, living in
      community (noninstitutionalized) settings. Data on dietary intakes and behaviors
      were obtained from the US Department of Agriculture's Continuing Survey of Food
      Intakes by Individuals (CSFII), 1994-96. Food security data were obtained from
      the 1999 Current Population Survey (CPS), conducted by the US Census Bureau. For
      both the CSFII and the CPS, sampling weights were used to generate nationally
      representative estimates. We found that lower-income elderly consume
      significantly fewer calories than higher-income elderly, fewer servings of major
      Food Guide Pyramid food groups, and most nutrients. Approximately 6% of elderly
      households report some degree of food insecurity. Although food and nutrition
      assistance programs can benefit elderly individuals, many do not participate.
      Many lower-income elderly also face physiological and social obstacles to
      obtaining a healthful diet. How best to meet these varied needs is a challenge
      for nutrition educators, researchers, and policy makers.

PMID- 12047828
TI  - Nutrition education for the healthy elderly population: isn't it time?
AB  - In the United States, people are living longer, healthier lives. A major goal of
      our public health system is to maintain health among successful agers and prevent
      or delay chronic disease morbidity. Major strides are being made in identifying
      the dietary needs of elderly people that are different from those of younger
      adults. However, nutrition education programs to promote those dietary needs have
      lagged behind. This report reviews dietary needs, demographic information, and
      recent nutrition policies for older adults as a basis for nutrition education
      programs. This report suggests that it is time to keep pace with recent findings
      and develop national and state-sponsored programs that will provide nutrition
      education and information transference to older people in the communities.

PMID- 12047829
TI  - Extending the reach of nutrition education for older adults: feasibility of a
      Train-the-Trainer approach in congregate nutrition sites.
AB  - Low-income older adults are difficult to reach with nutrition education. This
      study examines the feasibility of a Train-the-Trainer approach using congregate
      nutrition site (CNS) managers to deliver nutrition education. The study suggests
      that CNS managers were receptive to the role of trainer, CNS participants were
      satisfied with this method, and the acceptability of managers as trainers did not
      vary with participants' levels of risk of malnutrition. Although the sample size
      (53 participants and 4 managers) and convenience sampling method limit
      generalizability, the promising results suggest the potential benefits of this
      method and the need for further study.

PMID- 12047832
TI  - Caregiver connections: a caregiver support and continuing education system.

PMID- 12047830
TI  - Nutrition education may reduce burden in family caregivers of older adults.
AB  - The chronic, demanding nature of family caregiving for frail older adults creates
      a high degree of stress for caregivers, called caregiver burden. Caregiver burden
      compromises caregivers' emotional and physical health and health-promoting
      behaviors. Deterioration in caregivers' health and nutritional status may put
      caregivers at risk for chronic disease, diminish the ability of caregivers to
      provide care, and impair the quality of life experienced by caregivers and care
      recipients. Nutrition education may help reduce caregiver stress and maintain
      caregivers' health and well-being. Mediating caregiver stress may allow family
      caregivers to meet their societal role, which has intensified because of health
      care cost containment.

PMID- 12047833
TI  - Seniors Surf the Web: enhancing older adults' computer skills through a Website
      incorporating nutrition, health, and aging issues.

PMID- 12047834
TI  - Nutrition To Go: a nutrition newsletter for older, limited-resource, home
      delivered meal participants.

PMID- 12047837
TI  - Who we are and how we eat: a qualitative study of identities in food choice.
AB  - OBJECTIVE: The study sought to develop a theoretical understanding of identities
      related to eating. DESIGN: A grounded theory approach and open-ended, in-depth
      interviews were used to examine identity and eating from the perspectives of
      adults. PARTICIPANTS: Seventeen middle-class, white adults (nine women, eight
      men) were purposely recruited to vary in gender, age, household composition, and
      ways of eating using convenience and snowball sampling. DATA ANALYSIS: Interview
      transcripts were analyzed using the constant comparative method. RESULTS:
      Identities involved in participants' food choices related to usual or preferred
      eating behaviors, personal traits, reference groups, and social categories.
      Participants varied in the number, type, and complexity of identities involved in
      eating. Identities were reported to be both stable and dynamic over time and were
      shaped by participants' life course experiences. Participants varied in the
      attention they paid to evaluation and monitoring of identities related to eating,
      the extent to which they enacted identities in eating, and how they managed
      identity conflicts. IMPLICATIONS: The concept of identity may help researchers
      understand food choice processes and assist practitioners in recognizing the
      multiple meanings that people bring to and derive from eating.

PMID- 12047838
TI  - Role of food prepared away from home in the American diet, 1977-78 versus 1994
      96: changes and consequences.
AB  - OBJECTIVE: To examine changes, between 1977-78 and 1994-96, in the quantity and
      quality of food Americans consumed that was prepared at home versus away from
      home. DESIGN: Data were obtained from nationwide surveys of food consumption
      conducted by the US Department of Agriculture (USDA) in 1977-78 and 1994-96. To
      maximize comparability, we used "day 1" dietary data, which both surveys
      collected via 24-hour recall. SUBJECTS/SETTINGS: Individuals 2 years of age and
      over were selected. USDA sampling weights were used to generate nationally
      representative estimates. VARIABLES MEASURED: We categorized foods by preparation
      at home or at restaurants, fast-food establishments, schools/day care, and other
      non-home locations. We assessed percent calories from total fat and saturated
      fat, and the cholesterol, sodium, fiber, calcium, and iron densities of foods
      prepared at home versus those prepared away from home. STATISTICAL ANALYSES: T
      tests were calculated using accepted procedures to adjust for survey design
      effects. RESULTS: Between 1977-78 and 1994-96, consumption of food prepared away
      from home increased from 18% to 32% of total calories. Meals and snacks based on
      food prepared away from home contained more calories per eating occasion, and
      "away" food was higher in total fat and saturated fat on a per-calorie basis than
      at-home food. "Away" food contained less dietary fiber, calcium, and iron on a
      per-calorie basis. Among adults but not children, food prepared away from home
      was more sodium and cholesterol dense. IMPLICATIONS: When developing intervention
      messages and strategies, nutrition educators need to be aware of the increasing
      role of "away" food in Americans' diets.

PMID- 12047839
TI  - Culturally relevant nutrition education improves dietary quality among WIC
      eligible Vietnamese immigrants.
AB  - OBJECTIVE: To provide culturally appropriate nutrition education to improve the
      diets of Vietnamese women. DESIGN: A total of 152 homemakers were recruited to
      participate in a nutrition education project, with 76 receiving the intervention
      and 76 serving as the control group. SUBJECTS/SETTING: Non-English-speaking women
      eligible for the Special Supplemental Nutrition Program for Women, Infants and
      Children (WIC) with incomes below 185% of the poverty level living in 5
      California counties. INTERVENTION: Bicultural, bilingual Vietnamese-American
      nutrition education assistants taught 5 to 7 lessons in the Vietnamese language
      using nutrition education materials written in the Vietnamese language by 2
      bilingual, bicultural nutritionists. MAIN OUTCOME MEASURES: Twenty-four-hour food
      recalls were obtained before and after the 8-week interval on the treatment and
      control groups. STATISTICAL ANALYSIS: To examine if there were changes over time
      in nutrient intake and nutrient density within groups, matched pair t tests were
      done. Analysis of covariance techniques determined differences between groups.
      McNemar tests determined if, within groups, there were changes over time in food
      groups consumed. Chi-square techniques determined changes between groups.
      RESULTS: Over time, the number of treatment group participants who had at least
      one serving from each food group (P <.01), and who had the recommended number of
      servings from each food group (P <.05), significantly increased in comparison to
      the control group. Over time, the dietary nutrient density of calcium,
      riboflavin, and vitamin B6 (P <.05), as well as potassium (P <.01), of treatment
      group participants significantly improved in comparison to the control group.
      IMPLICATIONS: With training, bilingual, bicultural women can effectively deliver
      culturally relevant nutrition education to their peers.

PMID- 12047840
TI  - Which fourth-grade children participate in school breakfast and do their parents
      know it?
AB  - OBJECTIVE: To explore fourth-graders' school breakfast participation by gender
      and race (black, white) and examine the extent to which parents' responses to
      "Does this child usually eat school breakfast?" reflected their children's
      participation. DESIGN: Parents answered "yes" or "no" to the questions printed on
      consent forms. Observers documented which children participated in school
      breakfast on 26 to 51 randomly selected days per school during 24 weeks in the
      1999-2000 school year. SUBJECTS: 357 children recruited from all 22 fourth-grade
      classes from 6 schools in 1 public school district. VARIABLES MEASURED:
      Participation rate, participation rate grouping [usually participated (>or=50% of
      days observed), did not usually participate (< 50% of days observed)].
      STATISTICAL ANALYSES PERFORMED: Komolgorov-Smirnov tests, McNemar's test.
      RESULTS: Median participation rate was 37.5% overall. Distribution of
      participation rates differed significantly by race (K-S test, P <.001) but not
      gender. There was a significant difference in the percentage of parents who said
      "yes" or "no" compared to children's usual participation grouping (McNemar test,
      P <.001). Of parents who said "yes," 66% of children usually participated; of
      parents who said "no," 92% of children did not usually participate. IMPLICATIONS:
      Children, not parents, must be the source for learning about what children eat at
      school.

PMID- 12047841
TI  - Fourth-grade children's consumption of fruit and vegetable items available as
      part of school lunches is closely related to preferences.
AB  - OBJECTIVE: To use data from observations and interviews to document fourth
      graders' preferences for, and consumption of, fruits compared to vegetables
      available as part of school lunches. DESIGN: Observations and interviews were
      conducted for studies regarding the impact of time interval between eating and
      reporting on the accuracy of children's school lunch recalls. SUBJECTS/SETTINGS:
      Children were recruited from up to 4 schools in one district during 3 school
      years; 63% agreed to participate. Randomly selected children (n = 237) were each
      observed eating school lunch once and were interviewed (regarding items eaten and
      preferences for items eaten) within 11/2 hours or the next morning. MAIN OUTCOME
      MEASURES: Observed consumption of servings of items available as part of school
      lunch was recorded as none, taste, little bit, half, most, and all. Response
      options for preferences for items available as part of school lunch were liked
      not at all, a little, and a lot. STATISTICAL ANALYSES PERFORMED: Mixed-model
      analysis of variance. RESULTS: Preferences were higher for fruits than
      vegetables. As preferences increased, consumption increased (P <.0001).
      Consumption of fruits compared to vegetables was similar after adjusting for
      preferences. IMPLICATIONS: Research is needed to understand how to increase
      children's preferences for vegetables as a means of increasing consumption.

PMID- 12047842
TI  - Development of a body image program for adult women.

PMID- 12047843
TI  - Nutrition to grow on: a garden-enhanced nutrition education curriculum for upper
      elementary schoolchildren.

PMID- 12047844
TI  - How to escape the bottleneck of medicinal chemistry.

PMID- 12047845
TI  - Enzyme clicks together its own inhibitor.

PMID- 12047846
TI  - New assays for measuring prions reassure FDA.

PMID- 12047847
TI  - Novel templates for rapid protein separation.

PMID- 12047850
TI  - Case study: The London Biotechnology Network - a people thing.

PMID- 12047851
TI  - Dynamite approach to delicate complex scaffolds.

PMID- 12047852
TI  - Don't underestimate the power of VS.

PMID- 12047853
TI  - Conquering the proteome.

PMID- 12047855
TI  - Whole-animal cellular and molecular imaging to accelerate drug development.
AB  - In the past decade, new technologies (genomics), chemistries and high-throughput
      (HT) in vitro assays have played a large role in changing the paradigm of drug
      discovery and development. These technologies have enabled many more targets and
      potential lead compounds to be introduced into drug development. However, since
      1996, the number of drug approvals per year has been decreasing. This reduced
      pipeline has now compromised the ability of biopharmaceutical companies to
      deliver the double-digit growth levels that investors expect. This review
      explores what is lacking in the drug discovery and development process that has
      caused such a dearth of new chemical entities (NCEs), and looks at how new in
      vivo imaging technologies might provide an answer in the form of more predictive
      animal models.

PMID- 12047856
TI  - Discovery, innovation and the cyclical nature of the pharmaceutical business.
AB  - Unlike many recent articles, which paint the future of the pharmaceutical
      industry in gloomy colours, this article provides an optimistic outlook. It
      explores the foundations on which the pharmaceutical industry has based its
      outstanding successes. Case studies of important drug classes underpin the
      arguments made and provide the basis for the authors' argument that recent
      technological breakthroughs and the unravelling of the human genome will provide
      a new wave of high quality targets (substrate) on which the industry can build.
      The article suggests that in a conducive environment that understands the
      benefits that pharmaceuticals provide to healthcare, those players who can base
      their innovation on a sufficient scale and from a large capital base will reshape
      the industry.

PMID- 12047857
TI  - Hydrogels: from controlled release to pH-responsive drug delivery.
AB  - Hydrogels are one of the upcoming classes of polymer-based controlled-release
      drug delivery systems. Besides exhibiting swelling-controlled drug release,
      hydrogels also show stimuli-responsive changes in their structural network and
      hence, the drug release. Because of large variations in physiological pH at
      various body sites in normal as well as pathological conditions, pH-responsive
      polymeric networks have been extensively studied. This review highlights the use
      of hydrogels (a class of polymeric systems) in controlled drug delivery, and
      their application in stimuli-responsive, especially pH-responsive, drug release.

PMID- 12047860
TI  - Transforming the genome to drug discovery.

PMID- 12047861
TI  - Electroporation and ultrasound for gene and drug delivery.

PMID- 12047862
TI  - Vaccinating against ticks.

PMID- 12047863
TI  - A vaccine against atherosclerosis.

PMID- 12047866
TI  - Buttered bread, odd socks and knotted rope--urban myths or scientifc fact?

PMID- 12047867
TI  - Toxicoproteomics: learning to walk before it can run.

PMID- 12047868
TI  - The feedback cycle of conventional and virtual screening.

PMID- 12047871
TI  - Structural biology in drug design: selective protein kinase inhibitors.
AB  - Protein kinases have a fundamental role in signal transduction pathways, and
      aberrant kinase activity has been observed in many diseases. In recent years,
      kinase inhibition has become a major area for therapeutic intervention and a
      variety of kinase inhibitor pharmacophores has been described. This review
      illustrates some of the efforts and results in the field of structure-based
      design of protein kinase inhibitors. The methods and results discussed here
      illustrate the power of structure-based design in lead discovery, for example via
      virtual screening and in guiding the optimization of the pharmacological
      properties of these molecules.

PMID- 12047873
TI  - Metabolic modeling: a tool of drug discovery in the post-genomic era.
AB  - The Human Genome Project, DNA microarrays, proteome chips and metabolic profiles,
      among others, are generating unprecedented amounts of valuable information about
      the genetic and metabolic responses of organisms to stimuli. This wealth of
      information poses a great scientific challenge, namely the development of novel,
      effective methods for functional analysis and interpretation. It is proposed here
      that biomathematical systems models must accompany data generation and
      management. A particularly effective framework for this purpose is canonical
      modeling based on Biochemical Systems Theory. The key concept of this theory is
      the formulation of biological phenomena as systems of differential equations, in
      which all processes are represented as products of power-law functions.

PMID- 12047872
TI  - Engineering cellular microenvironments to improve cell-based drug testing.
AB  - Recent progress in the biology of cell adhesion is enabling cell culture models
      to better reproduce in vivo functions. Cues from adhesion to extracellular matrix
      and neighboring cells are important regulators of cell behaviors. The recent
      adaptation of semiconductor tools to spatially organize cells and their adhesions
      has enhanced our ability to engineer cell functions ex vivo. By using these tools
      to create more in vivo-like cultures, cell-based drug discovery and target
      validation could be improved. This review explores the biological advances made
      by these microfabrication tools and discusses how they could enable high
      throughput cell-based assays.

PMID- 12047878
TI  - Bioinformatics and information technology: reshaping the drug discovery process.

PMID- 12047879
TI  - Bio- and chemo-informatics beyond data management: crucial challenges and future
      opportunities.
AB  - Bio- and chemo-informatics are now thought to be crucial to the success and
      integration of biotechnology and drug discovery. Research in this area has
      expanded to go beyond data- and information-management. Here, we review exemplary
      areas, such as target identification and validation, virtual screening, and
      prediction of downstream characteristics of leads, where further research will
      play a key role in progressing the field.

PMID- 12047880
TI  - Protein-interaction networks: from experiments to analysis.
AB  - Functional proteomics approaches aim to characterize comprehensively the function
      of gene products, and provide a first-level understanding of cellular mechanisms.
      Here, we review recent techniques for the construction and prediction of large
      scale protein-interaction networks, with a particular emphasis on computational
      processing steps and comparative assessment of the reliability and completeness
      of the various approaches. We also discuss the use of protein-interaction network
      information in functional annotation and in the generation of higher-level
      biological hypotheses on pathways.

PMID- 12047881
TI  - Statistical intelligence: effective analysis of high-density microarray data.
AB  - Microarrays enable researchers to interrogate thousands of genes simultaneously.
      A crucial step in data analysis is the selection of subsets of interesting genes
      from the initial set of genes. In many cases, especially when comparing genes
      expressed in a specific condition to a reference condition, the genes of interest
      are those which are differentially regulated. This review focuses on the methods
      currently available for the selection of such genes. Fold change, unusual ratio,
      univariate testing with correction for multiple experiments, ANOVA and noise
      sampling methods are reviewed and compared.

PMID- 12047882
TI  - In silico identification of novel therapeutic targets.
AB  - The availability of the human genome sequence is a 'once in a lifetime'
      opportunity for scientists to uncover all possible human drug-targets. As the
      sequence is very large, the best way to identify new genes rapidly is by
      computational (in silico) methods. There are now many examples in which
      pharmaceutical companies have identified genes of interest initially by in silico
      analysis. High-throughput data-generation techniques, such as microarray
      analysis, are key to the generation of human genome data. Bioinformatics
      techniques are therefore certain to play an increasingly important role in drug
      discovery.

PMID- 12047883
TI  - Genome annotation techniques: new approaches and challenges.
AB  - As more of the human genome draft sequence is finished, and genomes from other
      organisms begin to be sequenced, the demand for accurate and reliable genome
      annotation will increase significantly. To facilitate this industrial-scale
      genome annotation, automated bioinformatics solutions are increasingly required.
      As a result, automatic genome annotation systems have become more important in
      gene discovery within recent years. The design of such large-scale bioinformatics
      systems is an evolving and dynamic field, based on central cores of
      bioinformatics software tools and relational databases. Not only must these
      systems efficiently manage and integrate large volumes of genomic data, but they
      must also deliver accurate gene predictions and effectively distribute annotation
      data to the biosciences community.

PMID- 12047884
TI  - Bioinformatics: the role and limitations of patents.
AB  - The worldwide market for bioinformatics tools and services is estimated, by some,
      to exceed US$40 billion within the next five years. As with other biotech
      companies, patent protection will be key to survival in the marketplace. Although
      the total number of issued bioinformatics patents is still small, virtually all
      aspects of bioinformatics constitute patentable subject matter, and the
      opportunity to generate intellectual property value from investment in
      bioinformatics should not be neglected.

PMID- 12047885
TI  - Predicting ADME properties in silico: methods and models.
AB  - Unfavourable absorption, distribution, metabolism and elimination (ADME)
      properties have been identified as a major cause of failure for candidate
      molecules in drug development. Consequently, there is increasing interest in the
      early prediction of ADME properties, with the objective of increasing the success
      rate of compounds reaching development. This review explores in silico approaches
      and selected published models for predicting ADME properties from chemical
      structure alone. In particular, we provide a comparison of methods based on
      pattern recognition to identify correlations between molecular descriptors and
      ADME properties, structural models based on classical molecular mechanics and
      quantum mechanical techniques for modelling chemical reactions.

PMID- 12047886
TI  - Text-based knowledge discovery: search and mining of life-sciences documents.
AB  - Text literature is playing an increasingly important role in biomedical
      discovery. The challenge is to manage the increasing volume, complexity and
      specialization of knowledge expressed in this literature. Although information
      retrieval or text searching is useful, it is not sufficient to find specific
      facts and relations. Information extraction methods are evolving to extract
      automatically specific, fine-grained terms corresponding to the names of entities
      referred to in the text, and the relationships that connect these terms.
      Information extraction is, in turn, a means to an end, and knowledge discovery
      methods are evolving for the discovery of still more-complex structures and
      connections among facts. These methods provide an interpretive context for
      understanding the meaning of biological data.

PMID- 12047887
TI  - The potential of Internet computing for drug discovery.
AB  - Large-scale, high precision drug discovery calculations, such as predicting
      protein folding or small-molecule protein inhibitors, have frustrated
      computational chemists because the supercomputers currently available are
      insufficiently powerful. The increasing power of PCs offers an alternative
      approach by harnessing 'idle time' from corporate and home computers that are
      connected to the Internet or an intranet. However, although the approach has the
      potential of offering hundreds or thousands of years of computer time per elapsed
      day, the architecture constraints require computational chemists to choose their
      methods and applications with care. Some algorithms, such as those for molecular
      simulations, are generally not appropriate, whereas virtual screening of
      molecules for protein inhibition works well.

PMID- 12047895
TI  - A colorimetric assay for 7-dehydrocholesterol with potential application to
      screening for Smith-Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS; MIM 270400) is a genetic disorder characterized
      by hypocholesterolemia and elevated 7-dehydrocholesterol (7DHC) levels resulting
      from mutations affecting 7-dehydrocholesterol reductase. We describe a
      colorimetric assay for 7DHC with potential application to large-scale screening
      for SLOS. Reaction of 7DHC and its esters with the Liebermann-Burchard reagent
      resulted in a brief initial absorbance at 510 nm (pink color) followed by an
      absorbance at 620 nm (blue color) after 2 min, while cholesterol samples were
      essentially colorless. The assay could identify typical SLOS blood samples by
      their pink color and increased absorbance at 620 nm after 2 min. Colorimetric
      identification of mild SLOS cases requires monitoring of the transient absorbance
      at 510 nm, which must be detected immediately after rapid, consistent mixing of
      the reagents. The need for special mixing devices and rigorous validation
      precludes sporadic use of the assay for diagnosing suspected SLOS cases. We also
      studied the stability of 7DHC in dried SLOS blood spots on Guthrie cards, which
      are widely used for archiving neonatal blood. Decomposition of 7DHC was
      effectively retarded by storage at low temperature and by precoating of the cards
      with antioxidants. The combined results provide a foundation for development of a
      simple, automated test for SLOS screening.

PMID- 12047896
TI  - Stabilization of polymerized vesicular systems: an application of the dynamic
      molecular shape concept.
AB  - A series of glycolipid surfactants derived from
      Tris(hydroxymethyl)acrylamidomethane (THAM) and bearing hydrocarbon or
      perfluorocarbon tails and an acryloyl group attached to their polar head was
      prepared to explore the aqueous behavior of the supramolecular systems they form.
      The dispersion of surfactants was achieved in water under ultrasonication
      conditions. Hydrocarbon compounds give heterogeneous vesicular assemblies. In the
      case of perfluorocarbon derivatives homogeneous vesicles were obtained. However
      after 1-day storage, all these systems fuse. To stabilize these vesicles,
      polymerization by ultra violet (UV) irradiation was carried out. During this
      reaction, a precipitation in water was observed for the hydrocarbon surfactants,
      whereas fluorocarbon structures provide stable vesicles without any alteration of
      their size. According to these results, the polymerization process was achieved,
      in the case of hydrocarbon glycolipid, in the presence of different cosurfactants
      bearing a single hydrocarbon tail or a polyhydroxylated head and a cholesterol
      terminus. In such conditions, homogeneous stable vesicles were prepared.
      Moreover, the THAM derived telomers bearing a cholesterol terminus were able to
      stabilize and reduce the size of vesicles formed with synthetic glycolipid
      surfactants. The drug encapsulation ability of these systems was investigated by
      measurement of the release kinetics of a fluorescent dye, carboxyfluorescein
      (CF), before and after polymerization.

PMID- 12047897
TI  - The effect of metal cations on the phase behavior and hydration characteristics
      of phospholipid membranes.
AB  - To characterize the specificity of ion binding to phospholipids in terms of
      headgroup structure, hydration and lyotropic phase behavior we studied 1
      palmitoyl-2-oleoyl-phosphatidylcholine as a function of relative humidity (RH) at
      25 degrees C in the presence and absence of Li+, Na+, K+, Be2+, Mg2+, Ca2+, Sr2+,
      Ba2+, Zn2+ and Cu2+ ions by means of infrared (IR) spectroscopy. All divalent
      cations and Li+ shift the gel-to-liquid crystalline phase transition towards
      bigger RH values indicating stabilization of the gel state. The observed shift
      correlates in a linearly fashion with the electrostatic solvation free energy for
      most of the ions in water that in turn, is inversely related to the ionic radius.
      This interesting result was interpreted in terms of the excess chemical potential
      of mixing of hydrated ions and lipids. Calcium, zinc and partially lithium, cause
      a positive deviation from the linear relationship. IR spectral analysis shows
      that the carbonyl groups become more accessible to the water in the presence of
      Mg2+, Ca2+, Sr2+ and Ba2+ probably because of their involvement into the
      hydration shell of the ions. In contrast, Be2+, Zn2+ and Cu2+ dehydrate the
      carbonyl groups at small and medium RH. The ability of the lipid to take up water
      is distinctly reduced in the presence of Zn2+ and, partially, of Cu2+ meaning
      that the headgroups have become less hydrophilic. The binding mode of Be2+ to
      lipid headgroups involves hydrolyzed water. Polarized IR spectra show that
      complex formation of the phosphate groups with divalent ions gives rise to
      conformational changes and immobilization of the headgroups. The results are
      discussed in terms of the lyotropic Hofmeister series and of fusogenic activity
      of the ionic species.

PMID- 12047898
TI  - Preparation and physical characterization of pure beta-carotene.
AB  - Pure all-trans beta-carotene has been prepared on the 10's of grams scale by
      isothermal Fractional Dissolution (FD) of commercial laboratory samples in
      tetrahydrofuran (THF). beta-Carotene purified in this way is black, with a faint
      brownish tinge. The electronic spectra of black samples extend into the near
      infrared, with end-absorption past 750 nm. Black samples react directly with
      dioxygen under mild conditions to yield the familiar orange or red powders. Pure
      beta-carotene rigorously obeys Beer's Law in octane over the entire UV-Vis
      spectral range, while commercial laboratory samples and recrystallized samples do
      not. NMR self-diffusion coefficient data demonstrate that beta-carotene exists as
      simple molecular solutions in octane and toluene. The anomalously high
      crystallinity of beta-carotene can be attributed (from analysis using molecular
      mechanics) to the facts that: (1) the number of theoretically possible conformers
      of beta-carotene is extremely small, and (2) only a small fraction of these (ca.
      12%, or 127) may actually exist in fluid phases.

PMID- 12047899
TI  - Activation of N-acylethanolamine-releasing phospholipase D by polyamines.
AB  - N-acylethanolamines including anandamide (an endogenous ligand of cannabinoid
      receptors) are biosynthesized from N-acyl-phosphatidylethanolamine (PE) by a
      phosphodiesterase of the phospholipase D type. The enzyme partially purified from
      the particulate fraction of rat heart hydrolyzed N-palmitoyl-PE to N
      palmitoylethanolamine with a specific activity of 50 nmol/min per mg protein at
      37 degrees C in the presence of 10 mM CaCl2. We found that the enzyme was highly
      activated in dose-dependent manner by polyamines like spermine, spermidine, and
      putrescine. Spermine was the most potent with an EC50 value around 0.1 mM, and
      increased the specific enzyme activity 27 fold up to 53 nmol/min per mg protein.
      However, a synergistic effect of spermine and the known activator (Ca2+ or Triton
      X-100) was not observed. The spermine-stimulated enzyme was also active with N
      arachidonoyl-PE (a precursor of anandamide). Thus, polyamines may function as
      endogenous activators to control the biosynthesis of anandamide and other N
      acylethanolamines.

PMID- 12047900
TI  - Synthesis and characterization of long-chain 1,2-dioxo compounds.
AB  - A series of long-chain methyl esters with vicinal oxo groups (1,2-diones; 1,2
      diketones) were synthesized by potassium permanganate-based oxidation of methyl
      esters of mono-unsaturated fatty acids. The presence of two additional carbonyl
      groups may facilitate the synthesis of other derivatives. The starting materials
      were selected in such a fashion to give the 1,2-dioxo moiety in consecutive
      positions from the methyl ester group. The compounds were characterized by mass
      spectrometry and nuclear magnetic resonance spectroscopy. In mass spectrometry,
      both electron and chemical ionization (methane as reagent gas) were investigated.
      The position of the dioxo moiety can be determined in both ionization modes,
      however, in electron ionization mode the corresponding fragment ions are
      considerably stronger. In electron ionization mode, a fragmentation mechanism
      depending on the position of the 1,2-dioxo moiety occurs while the spectra
      derived from chemical ionization mode are mainly characterized by peaks around
      the molecular ion with both ionization modes appearing suitable.

PMID- 12047901
TI  - Interaction among molecules in mixtures of ceramide/stearic acid,
      ceramide/cholesterol and ceramide/stearic acid/cholesterol.
AB  - To elucidate the interaction among the molecules which constitute intercellular
      lipids of stratum corneum, the phase diagrams in the binary mixtures of N
      octadecanoyl-phytosphingosine (CER)/stearic acid (SA) and CER/cholesterol (CHOL)
      were studied by differential scanning calorimetry and by small- and wide-angle X
      ray diffraction. These phase diagrams are mostly expressed by a eutectic type
      one. However, from their detailed analyses, it was revealed that in the phase
      diagram of CER/SA a new solid structure is formed just above the eutectic
      temperature. The lamellar spacing of the new structure is nearly equal to the
      length given by the sum of the two molecules of CER and/or SA, that is, in the
      lipid bilayer the hydrocarbon chains of CER and SA lie almost perpendicular to
      the lipid bilayer surface and the two kinds of molecules distribute
      homogeneously. On the other hand, in the binary mixture of CER/CHOL, CHOL
      molecules are apt to be isolated from the mixture. In a ternary mixture composed
      of equimolar lipids of CER, CHOL and SA, it was found that a pseudo-hexagonal
      structure takes place even in the solid state. This fact indicates that the three
      components are miscible and the hydrocarbon chains lie perpendicular to the lipid
      bilayer surface. We can draw the conclusion that the multi-component mixtures
      containing ceramide are apt to form the lamellar structure where even in the
      solid state the hydrocarbon chains lie perpendicular to the lipid bilayer surface
      and the components with hydrocarbon chains distribute homogeneously.

PMID- 12047902
TI  - An index of lipid phase diagrams.
AB  - There is a growing awareness of the utility of lipid phase behavior data in
      studies of membrane-related phenomena. Such miscibility information is commonly
      reported in the form of temperature-composition (T-C) phase diagrams. The current
      index is a conduit to the relevant literature. It lists lipid phase diagrams,
      their components and conditions of measurement, and complete bibliographic
      information. The main focus of the index is on lipids of membrane origin where
      water is the dispersing medium. However, it also includes records on
      acylglycerols, fatty acids, cationic lipids, and detergent-containing systems.
      The miscibility of synthetic and natural lipids with other lipids, with water,
      and with biomolecules (proteins, nucleic acids, carbohydrates, etc.) and non
      biological materials (drugs, anesthetics, organic solvents, etc.) is within the
      purview of the index. There are 2188 phase diagram records in the index, the bulk
      (81%) of which refers to binary (two-component) T-C phase diagrams. The remainder
      is made up of more complex (ternary, quaternary) systems, pressure-T phase
      diagrams, and other more exotic miscibility studies. The index covers the period
      from 1965 through to July, 2001.

PMID- 12047903
TI  - Toward a theory of intracrine hormone action.
AB  - A growing body of evidence indicates that in some cases, peptide hormones can
      function in the intracellular space. These findings are reviewed. In addition,
      this laboratory has made proposals regarding the origin, nature and function of
      intracrines--that is, intracellularly acting peptide hormones that also function
      in an autocrine, paracrine or endocrine manner. Here, these hypotheses are
      developed, and potential implications/applications of this point of view are
      discussed. Possible implications for cellular differentiation, cellular memory
      and hormonal responsiveness, as well as for the assumption of novel functions by
      intracellular regulatory proteins are discussed.

PMID- 12047904
TI  - Pharmacological comparison of rat and human melanocortin 3 and 4 receptors in
      vitro.
AB  - The melanocortin 3 and 4 receptors are G-protein-coupled receptors found in the
      hypothalamus with important role in regulation of the energy balance. In this
      study, we performed pharmacological comparison of the rat and human melancortin
      (MC) 3 and MC4 receptors. We transiently expressed the genes for these receptors
      individually in a mammalian cell line and determined the binding affinities to
      several MSH peptides. The results showed no major difference between the rat and
      human MC3 receptors while the rat MC4 receptor had higher affinity to several
      peptides compared with the human MC4 receptor. NDP-, alpha-, beta-, gamma-MSH,
      ACTH(1-24), HS014 and MTII had from 5- to 34-fold higher affinity for the rat MC4
      receptor, while SHU9119, HS024 and HS028 had similar affinity for both the MC4
      receptors. Pharmacological species difference have earlier been reported for the
      MC1 and MC5 receptors but this is the first report showing important differences
      between the rat and human MC4 receptors.

PMID- 12047905
TI  - Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat
      oxyntic mucosa on cAMP and IP(3) in rat osteoblast-like cells.
AB  - The existence of an osteotropic hormone (referred to as gastrocalcin) in the ECL
      cells of the gastric mucosa has been suggested. Both gastrin and an extract of
      the oxyntic mucosa lower blood Ca(2+) and stimulate Ca(2+) uptake into bone. The
      ECL cells are known to operate under gastrin control and, conceivably, gastrin
      lowers blood Ca(2+) indirectly by releasing the hypothetical ECL cell hormone. We
      have shown earlier that extracts of isolated ECL cells or of the granule/vesicle
      fraction of the oxyntic mucosa evoke a typical Ca(2+)-mediated second messenger
      response in osteoblastic cells. In the present study, we characterize this
      response further. An increase in intracellular inositol 1,4,5-trisphosphate
      (IP(3)) concentration was observed after treatment of UMR-106.01 osteoblast-like
      cells with extracts of ECL cells or granule/vesicle-enriched fractions from
      oxyntic mucosa. Intracellular cyclic adenosine monophosphate (cAMP)
      concentrations were not affected. Inhibition of phospholipase C (PLC) by U-73122
      abolished the increase in [Ca(2+)](i). Preincubation of UMR-106.01 cells with
      pertussis toxin, which blocks many G-proteins, did not prevent the increases in
      IP(3) and [Ca(2+)](i). It was also found that the novel peptide hormone ghrelin,
      produced in the A-like cells of the oxyntic mucosa, did not evoke any Ca(2+)
      signal in osteoblastic cells. The results indicate that the extracts mediate
      their effects through a pertussis toxin-insensitive mechanism, and that binding
      to a receptor leads to activation of PLC and production of IP(3) resulting in
      increased [Ca(2+)](i). The putative osteotropic hormone is distinct from ghrelin.

PMID- 12047906
TI  - Atrial natriuretic peptide inhibits iodide uptake and thyroglobulin messenger
      ribonucleic acid expression in cultured bovine thyroid follicles.
AB  - The involvement of atrial natriuretic peptide (ANP) in the regulation of thyroid
      gland is supported by the presence of high-affinity ANP receptors and the
      identification of the peptide in thyroid follicular cells. The aim of this work
      was to study the action of ANP on parameters of thyroid hormone biosynthesis and
      analyze the intracellular mechanism of the ANP action in cultured bovine thyroid
      follicles. The addition of ANP (0.1-10 nM) to the culture medium for 24 h
      inhibited the TSH (thyroid-stimulating hormone)-stimulated iodide uptake with a
      maximal inhibition at 1 nM ANP. When thyrocytes were incubated with 10 nM ANP the
      inhibitory effect slightly increased from 24 to 72 h. Thyroglobulin (Tg) mRNA
      expression was reduced by 1 and 10 nM ANP. After 24 h of treatment with the cGMP
      analogue, N(2),2'-O-dibutyrylguanosine 3':5'-cyclic monophosphate [(Bu)(2)cGMP]
      (0.1 and 1 mM), an inhibition of iodide uptake and Tg mRNA expression was
      obtained, evidencing a cGMP-mediated inhibitory signal in the thyroid cell. A
      reduction of the cAMP production was induced by incubation of thyroid follicles
      with 1 and 10 nM ANP for 24 h. Under a similar treatment the cGMP accumulation
      was increased only by 10 nM ANP. The inhibitory effect of ANP on Tg mRNA level
      was reverted in the presence of pertussis toxin, an inhibitor of the G(i)-protein
      mediated reduction of the adenylate cyclase activity. These results indicate an
      inhibitory action of ANP on parameters of thyroid hormone biosynthesis. A G(i)
      protein-mediated reduction of the cAMP production seems to be the main factor
      involved in the ANP action although a role of the cGMP pathway should not be
      discarded specially at high ANP levels.

PMID- 12047907
TI  - Effects of dehydration on renal aminopeptidase activities in adult male and
      female rats.
AB  - Aminopeptidases (APs) are important regulators of peptides directly involved in
      water homeostasis such as angiotensins (Ang) and vasopressin (AVP). Sex
      differences in water balance and differences in the effects of gonadal steroids
      on osmotic stimulation of vasopressin secretion have been reported. Since sex
      steroids may be involved, the gonadotropin response to osmotic stimuli may be
      different between males and females. The purpose of this study was to determine
      the behavior of angiotensinases, vasopressin-degrading activity and gonadotropin
      releasing hormone (GnRH)-degrading activity in the cortex and medulla of the
      kidney of dehydrated male and female rats. In the renal cortex, our results
      demonstrated an increase in Ang III-degrading activity in dehydrated males but
      not in females. This response may lead to an increased formation of Ang IV. This
      occurs with an increase in AspAP activity (which metabolizes Ang I to des-Asp(1)
      Ang I), with no changes in Ang II-degrading activity and also with increased
      levels of AVP-degrading activity in dehydrated animals. These results may suggest
      an increased cortical blood flow due to enhanced formation of Ang IV together
      with reduced availability of the vasoconstrictor agents Ang II and AVP in the
      renal cortex of dehydrated males. The results obtained in the renal medulla
      suggest the inhibition of the metabolism of Ang I to des-Asp(1)-Ang I, together
      with a reduced metabolism of Ang II and AVP in dehydrated males but not in
      females. These results suggest a prolonged action of Ang II and AVP, which could
      stimulate sodium and water reabsorption in the medulla of dehydrated males.
      Changes in APs after dehydration occur preferentially in males, which may explain
      in part the reported sex differences in water homeostasis. The present results
      suggest a physiologically relevant role for AP activities in water homeostasis.

PMID- 12047908
TI  - Aliphatic amino acids in helix VI of the AT(1) receptor play a relevant role in
      agonist binding and activity.
AB  - Angiotensin II (AII) AT(1) receptor mutants with replacements of aliphatic amino
      acids in the distal region of helix VI and the adjoining region of the third
      extracellular loop (EC-3) were expressed in Chinese hamster ovary (CHO) cells to
      determine their role in ligand binding and activation. The triple mutant [L262D,
      L265D, L268D]AT(1) (L3D) showed a marked reduction in affinity for AII and for
      non-peptide (losartan) and peptide ([Sar(1)Leu(8) ]AII) antagonists; in
      functional assays using inositol phosphate (IP) accumulation, the relative
      potency and the maximum effect of AII were reduced in L3D. Replacement of
      Leu(268) (in EC-3) and Leu(262) (in the transmembrane domain) by aspartyl
      residues did not cause significant changes in the receptor's affinity for the
      ligands and in IP production. In contrast, the point mutation L265D, at helix VI,
      markedly decreased affinity and ability to stimulate phosphatidylinositol
      turnover. Molecular modeling of the AT(1) receptor based on a recent crystal
      structure of rhodopsin, suggests that the side chain of Leu(265) but not that of
      Leu(262) is facing a cleft between helices V and VI and interacts with the lipid
      bilayer, thus helping to stabilize the receptor structure near the Lys(199)
      residue of helix V in the agonist binding site which is necessary for full
      activity.

PMID- 12047909
TI  - Structure-activity and structure-binding studies of des-Asp(1)-angiotensin I
      analogues on the rabbit pulmonary artery.
AB  - Structural modification of des-aspartate-angiotensin I (DAA-I), a
      pharmacologically active peptide, affected its actions on the precontracted
      cardiac and pulmonary sections of the rabbit pulmonary artery. The displacement
      of [125I]-Sar(1)-Ile(8)-angiotensin II by the DAA-I analogues from membrane
      homogenates of the whole pulmonary artery was also markedly reduced. Analogues
      that retained similar responses as DAA-I in the functional assays exhibited
      binding affinities of similar magnitude as DAA-I. Analogues that had no effect in
      the functional assay showed markedly reduced binding affinities. The first and
      fifth positions on DAA-I were identified as critical positions for activity as
      the replacement of Arg(2) and His(6) at these positions with alanine completely
      abolished activity and sharply reduced binding affinities. In contrast, the last
      two N-terminal amino acids of DAA-I can be modified substantially (D-amino acid
      and alanine substitution) without loss of activity or binding affinity. The
      identification of critical and noncritical amino acids would offer useful leads
      in the design of specific DAA-I antagonists.

PMID- 12047910
TI  - Food intake inhibition and reduction in body weight gain in lean and obese
      rodents treated with GW438014A, a potent and selective NPY-Y5 receptor
      antagonist.
AB  - Numerous reports have implicated theY5 receptor as the 'feeding' receptor
      mediating the orexigenic action of neuropeptide Y (NPY). This notion is supported
      by the correlation between the in vitro functional and binding activities of
      different peptide agonists and their potent stimulation of food intake in
      rodents. We have discovered a series of small molecule heterocycles with high
      affinity, selectivity, and functional antagonism for Y5 receptors.
      Intraperitoneal (i.p.) administration of GW438014A into rodents, resulted in a
      potent reduction of NPY-induced and normal overnight food intake. Brain levels of
      GW438014A were detected well in excess of its binding IC(50) for up to 3 h post
      dosing. Daily (i.p., BID, 10 mg/kg) administration of this compound to Zucker
      Fatty rats for a period of 4 days resulted in a marked decrease in the rate of
      weight gain and a reduction in fat mass. No effect on food intake was observed
      following oral administration of GW438014A (25-100 mg/kg), consistent with the
      poor oral bioavailability (<3%) and low brain levels observed.

PMID- 12047911
TI  - Effects of vasopressin on isolated rat adrenal chromaffin cells.
AB  - It has been demonstrated that arginine vasopressin (AVP) is synthesized not only
      in specific hypothalamic nuclei, but also in the adrenal medulla where it is
      thought to regulate adrenal functions by autocrine and paracrine mechanisms. In
      order to further characterise the effects of AVP on rat adrenal chromaffin cells,
      we examined: (a) the mRNA expression for V(1a) and V(1b) AVP receptors in these
      cells; (b) the effects of AVP on the membrane potential and membrane currents
      measured with the whole-cell patch-clamp technique; and (c) effect of AVP on
      catecholamine release from single adrenal chromaffin cells measured with carbon
      fibre microelectrodes. Reverse transcription-polymerase chain reaction (RT-PCR)
      on tissue punch samples obtained from the adrenal medulla demonstrated message
      for both the V(1a) and V(1b) receptors, while material obtained from the adrenal
      cortex showed expression of the V(1a) receptor only. Single-cell RT-PCR conducted
      on acutely isolated chromaffin cells showed message for the V(1a) receptor in 84%
      of cells, while 38% of cells also contained message for the V(1b) receptor
      (n=45). Under current-clamp recording, responses to AVP application (4-40 microM)
      were variable; 22/34 (65%) tested cells were depolarised, 29% hyperpolarised, and
      the remaining cells showed a biphasic response. Changes in membrane potential of
      either direction were dose-dependent and accompanied by a decrease in cell
      membrane resistance. Under voltage-clamp (V(hold)=-60 mV), AVP evoked inward
      current in 27/52 (52%) and outward current in 16/52 (31%) chromaffin cells. Both
      types of AVP-evoked responses were blocked by co-application of a nonselective
      V(1a)/V(1b) antagonist. Application of AVP evoked prolonged bursts of
      amperometric currents (indicative of catecholamine release) in 4/9 tested cells,
      but reduced the currents evoked by ACh application in all tested cells (n=7).
      These findings demonstrate a complex action of AVP on adrenal chromaffin cells,
      with individual adrenal chromaffin cells responding with either excitation or
      inhibition. This response pattern may be related to the expression of V(1)
      receptor subtypes.

PMID- 12047912
TI  - Angiotensin-(1-7) stimulates oxidative stress in rat kidney.
AB  - The effect of two different doses of angiotensin-(1-7) and angiotensin II on the
      oxidative stress generation was analyzed in rat kidney. Animals were injected
      intraperitoneally with a single dose of angiotensin-(1-7) or angiotensin II (20
      or 50 nmol/kg body weight) and killed 3 h after injection. Production of
      thiobarbituric acid reactive substances (TBARS), measured as indicator of
      oxidative stress induction, was significantly increased in rat kidney after Ang
      (1-7) administration up to 30% and 50% over controls, at 20 and 50 nmol/kg,
      respectively. Reduced glutathione (GSH), the most important soluble antioxidant
      defense in mammalian cells, showed a significant decrease of 13% and 20% at 20
      and 50 nmol/kg of angiotensin-(1-7), respectively. When the antioxidant enzyme
      activities were determined, it was found that catalase activity was not altered
      by the assayed angiotensin-(1-7) doses while superoxide dismutase and glutathione
      peroxidase activities were significantly reduced by injection of 20 nmol/kg (34%
      and 13%, with respect to controls) and 50 nmol/kg of angiotensin-(1-7) (54% and
      22%, respectively). In contrast, angiotensin II injections did not produce
      significant changes neither in TBARS levels nor in soluble and enzymatic defense
      parameters at the two doses used in this work. These results suggest that
      angiotensin-(1-7) is undoubtedly related to oxidative stress induction.

PMID- 12047913
TI  - Presence and release of SR-17 (chromogranin B(586-602)) in the porcine splenic
      nerve and its enzymatic degradation by CD26/dipeptidyl peptidase IV.
AB  - Using the pig splenic nerve as a model, we investigated the proteolytic
      processing of porcine chromogranin B (CgB) during its axonal transport. An ELISA
      was developed for SR-17 (CgB(586-602)), a novel CgB-derived peptide, originally
      found in the adrenal medulla. The results demonstrate that CgB is processed in an
      early stage during its axonal transport. Immunohistochemical data, based on a
      rabbit anti-SR-17 antiserum, show that the spleen CgB/SR-17 is exclusively
      present in the nerve endings. No SR-17 immunoreactivity (IR) was found in
      splenocytes. We also provide evidence that SR-17 is co-released with
      noradrenaline (NA) upon electrical stimulation of the splenic nerve. Its release
      is frequency-dependent and strongly enhanced in the presence of the alpha
      blocking agent phentolamine. In addition, we show that the new CgB-peptide can
      serve as a substrate for the lymphocyte surface glycoprotein CD26, also known as
      dipeptidyl peptidase IV (DPP IV), generating a new peptide ER-15 (CgB(588-602)).

PMID- 12047914
TI  - Healing-promoting effect of bombesin treatment on chronic gastric ulcer in rats.
AB  - To evaluate whether bombesin treatment has a facilitatory effect on the healing
      of chronic gastric ulcer, following the induction of ulcer by serosal application
      of acetic acid, rats were given bombesin (30 microg/kg/day; subcutaneously) or
      vehicle three times a day for 7, 14 or 21 days until they were decapitated.
      Neither food intake nor gastric emptying rate in either vehicle-treated or
      bombesin-treated groups was not statistically different from control rats.
      Similarly, ulcer indices and gastric myeloperoxidase (MPO) activities at the
      first and second weeks of injury were not different among the groups. However, in
      the 3-week ulcer group, bombesin treatment reduced tissue MPO level significantly
      back to control levels. Moreover, the analysis of the surface epithelium by
      scanning electron and light microscopy demonstrated a significant reduction in
      the severity of ulcers by bombesin treatment. Pretreatment with CCK antagonists
      (L-364,718 or L365,260; 25 micromol/kg/day) before bombesin treatment showed that
      neither of the CCK antagonists had a significant effect on the bombesin-mediated
      healing process, suggesting that CCK receptors are not involved in the action of
      bombesin. In accordance with the previous studies that show its acute
      gastroprotective effects, bombesin is also effective in promoting the healing
      process of chronic gastric ulcer in rats.

PMID- 12047915
TI  - Glucagon-like peptide-1 analogue LY315902: effect on intestinal motility and
      release of insulin and somatostatin.
AB  - LY315902 is an analogue of GLP-1 that yields a reduced clearance and longer half
      life. The aim of the study is to assess the effect of LY315902 on fasting
      gastrointestinal motility, somatostatin and insulin release. Sprague-Dawley rats
      were fitted with three bipolar electrodes, 15, 25 and 35 cm distal to the
      pylorus. The effect of LY315902 and GLP-1 on migrating myoelectric complex (MMC)
      cycle length, duration and propagating velocity of activity fronts was studied
      for 60 min in conscious animals. The effect of LY315902 and GLP-1 on fasting
      small bowel motility was dose-dependent and treatment with exendin (9-39)amide, a
      GLP-1 receptor antagonist, together with LY315902 and GLP-1 completely
      antagonised the inhibitory effect of LY315902 and GLP-1 on fasting small bowel
      motility. Pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)
      nitro-L-arginine (L-NNA) partly blocked the action of both LY315902 and GLP-1.
      Plasma insulin concentrations were not different from controls during infusion of
      LY315902 or GLP-1, while somatostatin concentrations were significantly higher
      during LY315902 and GLP-1 compared to saline. LY315902 has a longer duration of
      inhibitory action on the MMC than GLP-1, albeit similar effects on plasma insulin
      and somatostatin concentrations. The effect of LY315902 on motor control is
      mediated through the GLP-1 receptor and seems partly dependent on the L
      arginine/NO pathway.

PMID- 12047916
TI  - The influence of nitric oxide on basal and cholecystokinin-8-induced
      proliferation and apoptosis in the rat pancreas.
AB  - Nitric oxide (NO) is formed by different cell types in the pancreas. In this
      study, inhibition of endogenous nitric oxide by N(omega)-nitro-L-arginine (L-NNA)
      reduced the urinary excretion of NO(2)/NO(3) and raised serum L-arginine and the
      NO donator S-nitroso-N-acetylpenicillamine (SNAP) increased the urinary excretion
      of NO(2)/NO(3). The peptide cholecystokinin-8 (CCK-8) has a strong influence on
      exocrine pancreatic proliferation. Rat pancreas was excised and studied with
      regard to tissue weight, protein and DNA contents after 3 days of treatment with
      saline, L-NNA or SNAP given separately or combined with CCK-8. Further,
      proliferation of different pancreatic cells was studied with [3H]-thymidine
      incorporation and apoptotic activity was studied by analysing caspase-3 activity
      and histone-associated DNA fragments. The effects of L-NNA indicate that
      endogenous nitric oxide formation has a tonic inhibition on apoptosis in the
      pancreas during both basal condition and growth stimulation by CCK-8. In CCK
      induced hyperplasia, NO inhibits the proliferation of acinar cells but stimulates
      ductal cells. Endogenous NO may regulate the balance between proliferation and
      apoptosis and in a situation of growth stimulation by CCK-8, it has a tonic
      inhibition on both mitogenesis and apoptosis thus slowing down the acinar cell
      turnover in the pancreas.

PMID- 12047917
TI  - Altered secretion and processing of epidermal growth factor in adrenergic-induced
      growth of the rat submandibular gland.
AB  - The granular convoluted tubule (GCT) cells of the submandibular glands represent
      a major production site for epidermal growth factor (EGF). This study
      investigates EGF production in the submandibular glands in relation to beta
      adrenergic stimulation. Rats were treated with isoproterenol (beta-agonist),
      which caused up to a 400% increase in submandibular tissue weight after 3 weeks.
      The weight increase coincided with marked morphologic changes, with degranulation
      and an apparent decrement in the number of the GCT cells. Immunostaining against
      EGF revealed a reduction in the number of EGF-immunoreactive cells.
      Concomitantly, the glandular contents of 6-kDa EGF decreased from 12.86+/-3.42
      nmol/gland (mean+/-S.E.M.) in controls to 0.26+/-0.03 nmol/gland. EGF mRNA
      levels, expressed relative to total RNA levels, only tended to be reduced after 3
      weeks as judged from RT-PCR and in situ hybridization (ISH). The isoproterenol
      treated rats had increased output of EGF in the saliva, but the salivary
      secretion of protein was also increased. In both glandular tissue and saliva, gel
      filtration revealed partially processed high molecular weight forms of EGF in the
      isoproterenol-treated rats. These data indicate that isoproterenol treatment
      leads to a hyperstimulatory state of the GCT cells, which then causes depletion
      of the cellular stores of mature EGF, and most likely due to a shortened
      posttranslational transit, incomplete peptide processing.

PMID- 12047919
TI  - Stochastic models of some endemic infections.
AB  - Stochastic models are established and studied for several endemic infections with
      demography. Approximations of quasi-stationary distributions and of times to
      extinction are derived for stochastic versions of SI, SIS, SIR, and SIRS models.
      The approximations are valid for sufficiently large population sizes. Conditions
      for validity of the approximations are given for each of the models. These are
      also conditions for validity of the corresponding deterministic model. It is
      noted that some deterministic models are unacceptable approximations of the
      stochastic models for a large range of realistic parameter values.

PMID- 12047918
TI  - Immunochemical characterization and measurement of neuronal type nitric oxide
      synthase in human neuroblastoma NB-OK-1 cell using novel anti-synthetic peptide
      antibody and specific immunoassay system.
AB  - We developed a sensitive and specific immunoassay system for human neuronal
      nitric oxide synthase (hnNOS) using synthetic hnNOS(998-1024) peptide and anti
      hnNOS(998-1024) antibody. The novel antibody and radioimmunoassay system revealed
      a typical nNOS protein in human neuroblastoma NB-OK-1 cell (160 kDa, 180
      fmol/10(6) cells). The kinetic parameters of the enzyme were K(m)=4.88 microM and
      V(max)=4.34 pmol/min/mg protein for L-arginine. On incubation of NB-OK-1 cell for
      24 h, betamethasone phosphate decreased both nNOS-immunoreactivity (nNOS-IR) and
      enzymatic activity in the cell dose-dependently. On the other hand, pituitary
      adenylate cyclase activating polypeptide(1-38) (PACAP38) increased both nNOS-IR
      and enzymatic activity at concentrations of 10(-10) and 10(-9) M, but inversely
      decreased both at 10(-7) M. These suggest the positive and negative implications
      of endogenous NO in proliferation and differentiation of the cell, which support
      mitogenic activity of NO generated by nNOS in the cell. The present findings also
      provided evidence that the quantitative change of nNOS protein controls the
      integrated activity of the enzyme in the cell and, in turn, substantiate the
      validity and reliability of the present immunoassay system for hnNOS and its
      practical usefulness.

PMID- 12047920
TI  - Analysis of logistic growth models.
AB  - A variety of growth curves have been developed to model both unpredated,
      intraspecific population dynamics and more general biological growth. Most
      predictive models are shown to be based on variations of the classical Verhulst
      logistic growth equation. We review and compare several such models and analyse
      properties of interest for these. We also identify and detail several associated
      limitations and restrictions.A generalized form of the logistic growth curve is
      introduced which incorporates these models as special cases. Several properties
      of the generalized growth are also presented. We furthermore prove that the new
      growth form incorporates additional growth models which are markedly different
      from the logistic growth and its variants, at least in their mathematical
      representation. Finally, we give a brief outline of how the new curve could be
      used for curve-fitting.

PMID- 12047921
TI  - Stability properties of pulse vaccination strategy in SEIR epidemic model.
AB  - The problem of the applicability of the pulse vaccination strategy (PVS) for the
      stable eradication of some relevant general class of infectious diseases is
      analyzed in terms of study of local asymptotic stability (LAS) and global
      asymptotic stability (GAS) of the periodic eradication solution for the SEIR
      epidemic model in which is included the PVS. Demographic variations due or not to
      diseased-related fatalities are also considered. Due to the non-triviality of the
      Floquet's matrix associate to the studied model, the LAS is studied numerically
      and in this way it is found a simple approximate (but analytical) sufficient
      criterion which is an extension of the LAS constraint for the stability of the
      trivial equilibrium in SEIR model without vaccination. The numerical simulations
      also seem to suggest that the PVS is slightly more efficient than the continuous
      vaccination strategy. Analytically, the GAS of the eradication solutions is
      studied and it is demonstrated that the above criteria for the LAS guarantee also
      the GAS.

PMID- 12047922
TI  - Mathematical analysis of delay differential equation models of HIV-1 infection.
AB  - Models of HIV-1 infection that include intracellular delays are more accurate
      representations of the biology and change the estimated values of kinetic
      parameters when compared to models without delays. We develop and analyze a set
      of models that include intracellular delays, combination antiretroviral therapy,
      and the dynamics of both infected and uninfected T cells. We show that when the
      drug efficacy is less than perfect the estimated value of the loss rate of
      productively infected T cells, delta, is increased when data is fit with delay
      models compared to the values estimated with a non-delay model. We provide a
      mathematical justification for this increased value of delta. We also provide
      some general results on the stability of non-linear delay differential equation
      infection models.

PMID- 12047923
TI  - Optimal parametric sensitivity control for the estimation of kinetic parameters
      in bioreactors.
AB  - In this paper the well-known problem of optimal input design is considered. In
      particular, the focus is on input design for the estimation of kinetic parameters
      in bioreactors. The problem is formulated as follows: given the model structure
      (f,g), which is assumed to be affine in the input, and the specific parameter of
      interest theta;(k) find a feedback law that maximizes the sensitivity of the
      model output to the parameter under different flow conditions in the bioreactor
      and, possibly, minimize the input or state costs. Analytical solutions to these
      problems are presented. As an example a bioreactor with a biomass that grows
      according to the well-known Monod kinetics is considered.

PMID- 12047924
TI  - Effects of oocyte quality on development and transcriptional activity in early
      bovine embryos.
AB  - The objective of this study was to evaluate the effects of oocyte quality on in
      vitro development and the level of transcriptional activity in early bovine
      embryos. Cumulus-oocyte complexes (COC) were divided into six classes based on
      their cumulus investment and on the texture of the ooplasm. Embryos originating
      from oocytes with more than five layers of cumulus cells and with slight
      expansion of the cumulus and/or granulation in the ooplasm (class II) developed
      to the blastocyst stage as frequently as embryos originating from oocytes of
      class I which showed no signs of atresia (13.9 and 13.7% for classes I and II,
      respectively). Oocytes with fewer than five layers of cumulus cells and
      homogeneous ooplasm (class III) had lower cleavage (63.1%) than oocytes with more
      than five layers of cumulus cells (77.2 and 83.6% for classes I and II,
      respectively); however, development to the blastocyst stage was similar (12.7%).
      More advanced atresia such as the presence of granulations in oocytes with less
      than five layers of cumulus cells (class IV), the absence of cumulus (class V),
      or the presence of expanded cumulus with dark clumps (class VI) reduced cleavage
      (57.4, 35.9 and 56.3% for classes IV-VI, respectively) and blastocyst formation
      (3.5, 0.5 and 1.9% for classes IV-VI, respectively). We examined the effects of
      oocyte quality on the level of transcriptional activity in in vitro produced
      embryos at the 2-, 4-, 8-, 16-cell stage and in embryos remaining at the 8-cell
      stage while the majority had progressed to the 16-cell stage (8-cell delayed
      embryos) by labeling with 3H-uridine followed by RNA precipitation and
      scintillation counting. For each developmental stage, there was no significant
      effect of oocyte class on uptake and incorporation of 3H-uridine into embryos,
      with the exception of uptake at the 8-cell stage which was higher (P<0.05) in
      embryos from class V-VI oocytes. Labeled uridine uptake (in embryos from classes
      I-II and III oocytes) and incorporation (in embryos from oocytes of all classes)
      increased significantly at the 16-cell stage compared to earlier stages. Eight
      cell delayed embryos originating from classes I to IV oocytes incorporated
      significantly more 3H-uridine than normally developing 8-cell embryos. In
      conclusion, these results expand on previous work showing that oocytes with early
      signs of atresia have good development potential. No differences in
      transcriptional activity in embryos originating from different classes were
      detected. However, the results obtained with 8-cell delayed embryos indicated
      that transcriptional activity was determined by the interval after fertilization
      rather than the number of cell cycles.

PMID- 12047925
TI  - Effect of climate on the response to three oestrous synchronisation techniques in
      lactating dairy cows.
AB  - The reproductive efficiency of Friesian dairy cows was investigated in a three
      (oestrous synchronisation technique) x two (seasons of the year) factorial
      design. The 90 primiparous and multiparous cows (winter, n=42; summer, n=48) were
      allocated at random to three synchronisation treatments (n=30 cows per
      treatment). In treatment 1 (GPG), the cows were administered 15 mg PGF(2alpha)
      i.m. at 30 +/- 3 days postpartum, 100 microg GnRH i.m. at 51 +/- 3 days and 15 mg
      PGF(2alpha) 7 days later. A second 100 microg dose of GnRH was given after,
      further 2 days and fixed time AI occurred 16-20 h later. In treatment 2 (PG-PG),
      15 mg PGF(2alpha) was administered i.m. to each cow on three occasions at
      successive 14 days interval starting at 30 +/- 3 days postpartum and the cows
      were inseminated at observed oestrus following the third dose of PGF(2alpha).
      Cows in treatment 3 (PG) had a single administration of 15 mg PGF(2alpha) i.m. at
      57+/-3days postpartum and were inseminated as in treatment 2. Mean daily ambient
      temperature was 10.9 degrees C in winter (November-March) and 20.2 degrees C in
      summer (June-October). The cows were confined in an open-fronted shed and had ad
      libitum access to a complete diet with a 37:63 forage to concentrate ratio. Body
      condition score was assessed at 57 +/- 3 days postpartum. Cow rectal temperature
      at insemination, milk yield, reproductive data and climatic variables were
      recorded. Blood samples were collected for progesterone assay on days 4, 11, 18,
      25, 32, 39 and 46 post-AI from 54 of the cows (19 GPG; 17 PG-PG; 18 PG).
      Pregnancy rate to first AI was 36.7% (11/30) for GPG and 16.7% (5/30) for both PG
      PG and PG treatments. The difference was not significant. The cumulative
      pregnancy rate after third AI were GPG 83.3% (25/30), PG-PG 60.0% (18/30) and PG
      60.0% (18/30; P<0.057). The cumulative pregnancy rate for cows inseminated in the
      winter (81.0%; 34/42) was higher (P<0.01) than for those inseminated in the
      summer (56.3%; 27/48). The interval from calving to first service was shorter
      (P<0.05) in treatment PG-PG (65.4+/-1.3 days) than in PG (69.2+/-1.3 days). Mean
      plasma progesterone concentrations post-AI of pregnant cows were higher (P<0.001)
      for GPG cows than those for PG-PG and PG cows. Plasma progesterone levels of
      pregnant cows tended to be higher (P=0.087) in winter than in summer. In
      conclusion, although the cumulative pregnancy rate was higher for GPG cows, it
      may be appropriate to correct the nutrition and management of the herd before
      resorting to synchronisation techniques to improve animal reproductive
      performances.

PMID- 12047926
TI  - In vitro maturation and fertilization of bovine oocytes and in vitro culture of
      presumptive zygotes in the presence of bovine pestivirus.
AB  - A pathogen which has been shown to commonly contaminate in vitro bovine embryo
      production system is bovine pestivirus (bovine viral diarrhea virus). Three
      experiments were designed to evaluate the in vitro maturation (experiment I),
      fertilization (experiment II) and embryo development (experiment III) of immature
      oocytes, inseminated oocytes and presumptive zygotes in the presence of a bovine
      pestivirus (non-cytopathic, nCP type 1). The virus inoculum used was derived from
      a persistently infected cow. In experiment I, follicular oocytes (n=1257)
      recovered from slaughterhouse derived ovaries were randomly assigned to either a
      control group (n=578) which did not become exposed to bovine pestivirus and a
      treatment group (n=679) which was inoculated with bovine pestivirus (2.20-3.69
      log(10) TCID(50)/50 microl) at the time of commencement of in vitro maturation.
      Overall, there was no significant difference between the control and pestivirus
      inoculated oocytes in either the cumulus cell expansion rate (79+/-7.5% versus
      74+/-10.7%) or the nuclear maturation rate (89+/-4.8% versus 85+/-7.4%),
      respectively. In experiment II, in vitro matured oocytes (n=607) were inseminated
      either in the absence (control; n=301) or the presence of bovine pestivirus (4
      4.6 log(10) TCID(50)/50 microl; n=306). A significant (P<0.01) reduction in the
      overall number of fertilized oocytes with two well formed male and female
      pronuclei was observed in the treatment group compared to the control group
      (58.5+/-5.8% versus 73.3+/-3.6%, respectively). In experiment III, after in vitro
      maturation and fertilization, presumptive zygotes were randomly assigned to
      either a control group (n=139) which was not exposed to bovine pestivirus or a
      treatment group which was inoculated with bovine pestivirus (2.97-4.47 log(10)
      TCID(50)/30 microl; n=139). The zygotes were then cultured under mineral oil in
      an atmosphere of 88% N(2), 7% O(2) and 5% CO(2) at 39 degrees C. The morphologic
      appearance of the embryos was assessed 48 h after the commencement of culture,
      and then every 48 h up to days 7-8 after insemination. The 22% (31/139) and 3.6%
      (5/139) of the presumptive zygotes developed to the morula or blastocyst stage in
      the control and the bovine pestivirus inoculated groups, respectively (P<0.001).
      This study demonstrates that bovine pestivirus has a significant detrimental
      effect on in vitro fertilization and early in vitro embryo development.

PMID- 12047927
TI  - Effects of fetuin on zona pellucida hardening, fertilization and embryo
      development in cattle.
AB  - Mammalian oocytes can undergo spontaneous meiotic maturation when they are
      liberated from their follicles and cultured in vitro; however, the zona pellucida
      (ZP) becomes resistant to chymotrypsin digestion, or hardens, when spontaneous
      maturation occurs in serum-free medium. Schroeder et al. [Biol. Reprod. 43 (1990)
      891] described that fetuin, a component of fetal calf serum (FCS), inhibits ZP
      hardening during oocyte maturation. The aim of this experiment was to study the
      effect of the presence of cumulus cells and addition of hormones to maturation
      media on bovine zona hardening and embryo development in medium with and without
      fetuin. In Experiment I, different concentrations of fetuin were added to the
      maturation medium. The time necessary for digestion of 50% of the ZP (d50) was
      not different when oocytes were matured in presence of 10% FCS, 1mg/ml polyvinyl
      alcohol (PVA), or 4, 1 and 0.25mg/ml of fetuin; cleavage rates were also similar.
      However, significantly more blastocysts (P<0.05) were formed when FCS was used
      compared to PVA and 0.25mg/ml of fetuin. In Experiment II, we examined the
      influence of the presence of cumulus cells and hormones during the maturation of
      oocytes in media with PVA, BSA, FCS and fetuin. The d50 was significantly higher
      (P<0.05) when oocytes were matured in presence of cumulus cells. The cleavage
      rate of cumulus-intact oocytes was similar for all groups. However, when oocytes
      were partially stripped before maturation, the cleavage rate was significantly
      higher (P<0.05) when FCS or fetuin was used. In both stripped and non-stripped
      groups, significantly more blastocysts (P<0.05) were formed when oocytes were
      matured with FCS compared to BSA and PVA. These results indicate that zona
      hardening, as described for mouse and human oocytes, does not have a large effect
      on bovine cumulus-intact oocytes. Apparently fetuin can be used as a substitute
      for FCS during bovine oocyte maturation, since it leads to similar developmental
      rates as FCS in intact and partially stripped oocytes.

PMID- 12047928
TI  - Effects of beta-mercaptoethanol on formation of pronuclei and developmental
      competence of swamp buffalo oocytes.
AB  - This study was conducted to determine the effect of supplementing maturation
      medium with beta-mercaptoethanol (betaME) on pronuclei formation and
      developmental competence of swamp buffalo oocytes. Buffalo oocytes were matured
      in TCM199 medium either with 10mM betaME or without betaME supplementation for
      24h. In Experiment 1, oocytes were fixed and stained for cytological evaluation
      after in vitro fertilization (IVF). In Experiment 2, presumptive zygotes were
      cultured and their developmental competency was assessed. It was found that
      betaME significantly improved the proportion of oocytes that exhibited
      synchronous pronuclei formation (31.8+/-5.1% versus 17.9+/-3.3%, P<0.05). There
      were no significant differences between oocytes matured with or without betaME in
      their capability of developing into blastocyst-stage embryos (3.0+/-1.3% versus
      1.8+/-0.9%). However, blastocysts produced from oocytes matured in the presence
      of betaME appeared to develop faster than those from oocytes matured in the
      absence of betaME (P<0.05). Cavitation of embryos from oocytes matured in the
      presence of betaME occurred at 156 hpi, whereas those matured in the absence of
      betaME occurred at 180 hpi. Although in vitro production of blastocysts did not
      increase by addition of betaME to maturation medium, quality of blastocysts
      produced from oocytes matured in the presence of betaME was improved. This study
      provides information for further investigations on optimizing a system for in
      vitro production of swamp buffalo embryos.

PMID- 12047929
TI  - Passive immunization of rams (Ovis aries) against GnRH: effects on antibody
      titer, serum concentrations of testosterone, and sexual behavior.
AB  - The effect of immunoneutralization of gonadotropin-releasing hormone (GnRH) on
      serum concentrations of testosterone and sexual behavior was evaluated in
      sexually mature male sheep. In Experiment 1, GnRH1 rams (n=16) were passively
      immunized against GnRH (300 ml antiserum), control rams were either passively
      immunized against keyhole limpet hemocyanin (KLH, n=15) or surgically castrated
      (Wethers1, n=4). Sexual performance of the rams was assessed weekly for 3 weeks
      before and 6 weeks after immunization, using ovarihystertomized ewes actively
      immunized against GnRH. Experiment 2 evaluated the effects of repeated
      immunization. Rams were immunized with two aliquots (400 and 300 ml,
      respectively) of anti-GnRH sera (GnRH, n=5) or normal sheep serum (NSS, n=4), 2
      weeks apart. Surgically castrated animals were used as a second control group
      (Wethers2). Administration of anti-GnRH sera, but neither anti-KLH nor NSS sera,
      resulted in marked reduction (P<0.05) in serum concentrations of testosterone.
      Sexual behavior was not consistently affected by administration of one aliquot of
      anti-GnRH sera, however repeated immunizations resulted in more persistent
      reduction in serum concentrations of testosterone and more consistent suppression
      of sexual behavior.

PMID- 12047930
TI  - Effect of 2-deoxy-D-glucose on gonadotropins, prolactin and serum glucose
      concentrations in the mare.
AB  - In a variety of species, glucoprivation results in the suppression of the
      reproductive axis. Two experiments were performed to test the hypothesis that
      blockade of glucose metabolism via administration of the glucose inhibitor 2
      deoxy-D-glucose (2DG) to mares would cause a modification in gonadotropin and
      prolactin secretion. Long-term ovariectomized mares (Experiment 1, n=4) or ovary
      intact mares during the follicular phase of a synchronized estrous cycle
      (Experiment 2, n=4 per dose) were treated with 2DG. The dose of 2DG used in
      Experiment 1 was 100mg 2DG/kg BW, but because severe behavioral responses
      occurred, lower doses (50, 25, and 12.5mg 2DG/kg BW) were used for Experiment 2.
      In addition to the effects of 2DG, the pituitary responsiveness after
      glucoprivation was determined by an injection of gonadotropin-releasing hormone
      (100 microg) 6h post-treatment. In both experiments, treatment with 2DG was
      unaccompanied by changes in gonadotropin secretion or pituitary responsiveness.
      Mares treated with 100 mg 2DG/kg BW exhibited a significant increase in prolactin
      and mares treated with 100mg 2DG or 50mg 2DG/kg BW exhibited a significant
      increase in serum glucose concentrations, suggesting that glucoprivation was
      detected at these doses. Lower doses of 2DG did not cause significant alterations
      in prolactin or glucose levels. These results indicate that 2DG inhibits glucose
      utilization, but short-term glucoprivation via this metabolic inhibitor does not
      alter gonadotropin secretion in the mare. This lack of response to glucoprivation
      may reflect species differences in the response to glucoprivation or may be due
      to metabolic responses to the inhibition of glucose availability.

PMID- 12047931
TI  - Differential expression of cyclooxygenase-2 around the time of elongation in the
      pig conceptus.
AB  - Alterations in uterine luminal fluid composition as a result of conceptus
      estradiol-17beta production are believed to play a significant role in the loss
      of 30-40% of potential pig conceptuses. Shortly after the initiation of conceptus
      estradiol-17beta synthesis and secretion, the conceptuses are transformed from
      1cm spheres to 2-5cm tubular forms and finally to filamentous threads of variable
      length via a process known as elongation. We have attempted to characterize gene
      products whose expression is either initiated or terminated as the conceptus
      elongates. Using RNA fingerprinting, we determined that the inducible form of the
      rate-limiting enzyme in prostaglandin synthesis, cyclooxygenase-2, is expressed
      in the filamentous pig conceptus, but not in either the spherical or transitional
      morphologies. Furthermore, increased expression of cyclooxygenase-2 by the
      filamentous conceptus was associated with increases in the content of
      prostaglandins (particularly prostaglandin E(2)) found in uterine luminal fluid.

PMID- 12047932
TI  - The influence of pre- and post-ovulatory insemination on sperm distribution in
      the oviduct, accessory sperm to the zona pellucida, fertilisation rate and embryo
      development in sows.
AB  - The aim of present study was to investigate the influence of pre-compared with
      post-ovulatory insemination, on the distribution of spermatozoa in the oviduct,
      the accessory sperm counts on the zona pellucida and early embryonic development.
      Thirty-six crossbred multiparous sows (Swedish Landrace x Swedish Yorkshire) were
      artificially inseminated once either at 20-15 h before (group AIB) or at 15-20 h
      after (group AIA) ovulation by using a pooled semen of two boars. Thereafter,
      they were randomly allocated to one of five groups: slaughter at 5-6h after AI
      (group I-AIB), at 20-25 h after ovulation (groups II-AIB and II-AIA), at 70 h
      after ovulation (groups III-AIB and III-AIA), on day 11 (groups IV-AIB and IV
      AIA, first day of standing oestrus=day 1) and on day 19 (groups V-AIB and V-AIA).
      The plasma levels of oestradiol-17beta and progesterone differed significantly
      (P<or=0.05 and P<or=0.001, respectively) between AI before (group AIB) and after
      (group AIA) ovulation. All sows inseminated before ovulation (group I-AIB) had
      spermatozoa in the UTJ but this was found only in one of the late inseminated
      sows (group II-AIA). The number of oocytes with spermatozoa in the ZP differed
      significantly (P<or=0.001) between 'group II-AIB' and 'group II-AIA'. Comparing
      fertilisation rate, the fertilisation rate in 'group III-AIB' was significantly
      (P<or=0.001) higher than in 'group III-AIA'. A larger number of recovered embryos
      (on days 11 and 19) per sow in groups IV-AIB and V-AIB compared with IV-AIA and V
      AIA were found. The embryos in group IV-AIB were also larger than embryos in
      group IV-AIA. In group V-AIA, no embryos were found.In conclusion, the results of
      this study showed that if insemination was performed at 15-20 after ovulation in
      sows that still were in standing oestrus, the transport of spermatozoa to the UTJ
      and oviduct was impaired and a lower proportion of oocytes with accessory
      spermatozoa to the zona pellucida was found compared with insemination before
      ovulation. In the late inseminated sows, fertilised oocytes and developed embryos
      were observed up to day 11 but no embryos were found at day 19.

PMID- 12047933
TI  - Raman spectroscopy and imaging of beta-carotene in live corpus luteum cells.
AB  - Raman spectroscopy has been used to identify and locate beta-carotene within
      individual living luteal cells. The cells were either freshly prepared or
      cultured; the latter was incubated in the presence or absence of beta-carotene in
      the form of enriched bovine high-density lipoprotein. Luteal cells were
      investigated using several Raman spectroscopic and imaging techniques. These
      techniques did not give accurate concentration levels of beta-carotene within
      parts of the cell but illustrated the distribution of the molecule. Freshly
      prepared luteal cells were found to contain an appreciable concentration of beta
      carotene. Over a period of several days, the concentration gradually reduced to a
      nearly undetectable level; similar results were found for cells cultured in the
      absence of the beta-carotene. For cells cultured in the presence of beta
      carotene, the molecular concentration was maintained for as long as 2 weeks. The
      Raman spectra of fragmented cells showed that the beta-carotene is predominantly
      localised in the lipid-rich cell components, with the concentration highest in
      the microsomal fraction. The Raman imaging techniques revealed that beta-carotene
      was spread over the entire volume of the luteal cells with higher levels
      occurring at distinct sites, including the surface.

PMID- 12047935
TI  - Genetics of social behaviour in fire ants.
AB  - A recent study is the first to sequence a gene known to underlie a complex social
      phenotype. In the fire ant, Solenopsis invicta, a single allelic difference at
      the Gp-9 locus specifies the number of queens a colony has, and hence the social
      structure of the colony. Gp-9 appears to encode a protein implicated in chemical
      recognition of nestmates, consistent with workers determining queen number by
      selectively executing queens as a function of workers' and queens' Gp-9
      genotypes. Other Solenopsis species exhibit the same social and genetic
      polymorphism. This study pioneers the integrated understanding of the evolution
      of social behaviour at molecular, individual and social levels.

PMID- 12047936
TI  - Antisense RNAs everywhere?
AB  - In recent years, systematic searches of both prokaryote and eukaryote genomes
      have identified a staggering number of small RNAs, the biological functions of
      which remain unknown. Small RNA-based regulators are well known from bacterial
      plasmids. They act on target RNAs by sequence complementarity; that is, they are
      antisense RNAs. Recent findings suggest that many of the novel orphan RNAs
      encoded by bacterial and eukaryotic chromosomes might also belong to a
      ubiquitous, heterogeneous class of antisense regulators of gene expression.

PMID- 12047937
TI  - Haplotype diversity and the block structure of linkage disequilibrium.
AB  - Several recent studies indicate that patterns of linkage disequilibrium in the
      human genome cannot be reconciled with a uniform distribution of recombination
      events, but crossovers appear to be localized in short hot-spots that separate
      longer stretches of DNA. Markers within these low-recombination blocks show
      increased levels of linkage disequilibrium and very low haplotype diversity. This
      could simplify study of the genetic basis of complex diseases if causal variants
      are common.

PMID- 12047938
TI  - Purifying and directional selection in overlapping prokaryotic genes.
AB  - In overlapping genes, the same DNA sequence codes for two proteins using
      different reading frames. Analysis of overlapping genes can help in understanding
      the mode of evolution of a coding region from noncoding DNA. We identified 71
      pairs of convergent genes, with overlapping 3' ends longer than 15 nucleotides,
      that are conserved in at least two prokaryotic genomes. Among the overlap
      regions, we observed a statistically significant bias towards the 123:132 phase
      (i.e. the second codon base in one gene facing the degenerate third position in
      the second gene). This phase ensures the least mutual constraint on
      nonconservative amino acid replacements in both overlapping coding sequences. The
      excess of this phase is compatible with directional (positive) selection acting
      on the overlapping coding regions. This could be a general evolutionary mode for
      genes emerging from noncoding sequences, in which the protein sequence has not
      been subject to selection.

PMID- 12047939
TI  - Growth and decline of introns.
AB  - To gauge the processes that might direct the length of introns, I studied the
      balance of indels (insertions or deletions, determined using Alu and LINE1
      retroposon repeats) and the density of these repeats in the introns of the human
      genome. The indel balance is biased in favour of deletions and correlated with
      the divergence of repeats. At fixed repeat divergence, the indel bias correlated
      with the intron size: the shorter the intron, the more deletions were favoured
      over insertions. This correlation with the intron size was stronger than with the
      gene-wide or isochore-wide parameters. The density of repeats (the number of
      repeats in a unit of intron length) correlated positively with the intron size.
      Thus, quite different mechanisms, the indel bias and the integration and/or
      persistence of retroposons, act in the same direction in regards to intron size,
      which suggests selection for the size of individual introns.

PMID- 12047940
TI  - A hot story from comparative genomics: reverse gyrase is the only
      hyperthermophile-specific protein.
AB  - I have looked for proteins that are present in all hyperthermophile genomes, but
      absent from all mesophile or thermophile genomes by using the phylogenetic
      pattern search program of the COG database. Surprisingly, this search retrieved
      only one such hyperthermophile-specific protein: reverse gyrase. This result
      emphasizes the importance of reverse gyrase in the adaptation of life to very
      high temperatures, and strengthens the idea that evolution of this enzyme was
      crucial in the origin of hyperthermophiles.

PMID- 12047941
TI  - Chick gene frenzy.
AB  - The BBSRC Chick Genomics and Biology Workshop was held at UMIST, Manchester UK
      from 15 to 16 December 2001.

PMID- 12047942
TI  - Evolutionary genomics: molecular evolution at the genomic scale.
AB  - The Symposium on Evolutionary Genomics was held in Atami, Japan, from 4 to 6
      November 2001.

PMID- 12047948
TI  - Recent emergence of the modern genetic code: a proposal.
AB  - This article proposes that the genetic code was not fully formed before the
      divergence of life into three kingdoms. Rather, at least arginine and tryptophan
      evolved after the diversification of archaea, bacteria and eukaryotes, and were
      spread by horizontal gene transfer. Evidence for this hypothesis is based on data
      suggesting that enzymes for biosynthesis of arginine and tryptophan, and for
      arginine tRNA ligase, have shorter divergence times than the underlying lineages.
      Also, many of these genes display "star" phylogenies. This proposal is an
      extension of the idea that the genetic code was unified because of the
      evolutionary pressure from horizontal gene transfer. These considerations further
      undermine the need to postulate the existence of a "last common ancestor"; a
      simpler model would be that multiple lineages gave rise to life today.

PMID- 12047949
TI  - The case of the monarch butterfly: a verdict is returned.
AB  - A publication reporting the harmful effects on the monarch butterfly of maize
      genetically modified to express insecticidal delta-endotoxins from the soil
      bacterium Bacillus thuringiensis (Bt) caused much public interest. A series of
      ecologically based studies were subsequently carried out to evaluate rigorously
      the impact of pollen from such crops and to quantify the risks. The results
      demonstrated that the commercial large-scale cultivation of current Bt-maize
      hybrids did not pose a significant risk to the monarch population. Further
      studies also demonstrated that Bt-expressing crops posed little risk to other
      nontarget insects, including beneficial insects such as pollinators and natural
      enemies.

PMID- 12047950
TI  - Unravelling heterochromatin: competition between positive and negative factors
      regulates accessibility.
AB  - Heterochromatin mediates many diverse functions in the cell nucleus, including
      centromere function, gene silencing and nuclear organization. The condensed
      structure of pericentromeric heterochromatin is associated with the presence of a
      regular arrangement of nucleosomes, which might be due in part to the underlying
      sequence of the satellite repeats. Recent studies identified methylation of the
      histone H3 tail as an epigenetic mark that affects acetylation and
      phosphorylation of histone tail residues and also acts as a recognition signal
      for binding of heterochromatin protein 1 (HP1). The decision to silence or
      activate heterochromatic genes appears to be the result of a balance between
      negative factors that promote the formation of condensed higher-order chromatin
      structure, and positively acting transcription factors that bind to regulatory
      sequences and activate gene expression.

PMID- 12047951
TI  - The rise and fall of SRY.
AB  - Comparisons between species reveal when and how SRY, the testis-determining gene,
      evolved. SRY is younger than the Y chromosome, and so was probably not the
      original mammal sex-determining gene that defined the Y. SRY is typical of genes
      on the Y chromosome. It arose from a gene on the proto-sex chromosome pair with a
      function (possibly brain-determination) in both sexes. It has been buffeted in
      evolution, and shows variation in copy number, structure and expression. And it
      is dispensable, having been lost at least twice independently in different rodent
      lineages. At the observed rate of attrition, the human Y chromosome will be gone
      in 5-10 million years. This could lead to the extinction of our species or to a
      burst of hominid speciation.

PMID- 12047952
TI  - Statistical issues with microarrays: processing and analysis.
AB  - The study of gene expression with printed arrays and prefabricated chips is
      evolving from a qualitative to a quantitative science. Statistical procedures for
      determining quality control, differential expression, and reproducibility of
      findings are a natural consequence of this evolution. However, problems inherent
      to the technologies have raised important issues of how to apply adequate
      statistical tests. As a consequence, statistical approaches to microarray
      research are not yet as routine as they are in other sciences. Statistical
      methods, tailored to microarrays, continue to be adapted and developed. We
      present an overview of these methods and of outstanding issues in their use and
      validation.

PMID- 12047956
TI  - Mouse models of prostate carcinogenesis.
AB  - In recent years, numerous mouse models have been generated that recapitulate
      salient features of prostate carcinogenesis in humans. Here we review progress in
      the generation and validation of mouse models for prostate cancer, discuss
      current limitations of these models, and highlight directions of future research.

PMID- 12047957
TI  - Genomics and health inequalities.

PMID- 12047958
TI  - Abnormal heart-rate recovery after exercise.

PMID- 12047959
TI  - Metastatic colorectal cancer: treatment challenges and quality of life.

PMID- 12047960
TI  - Magnetic-resonance imaging to assess Alzheimer's disease.

PMID- 12047961
TI  - Nitric oxide, phosphodiesterase inhibition, and adaptation to hypoxic conditions.

PMID- 12047962
TI  - Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial.
AB  - BACKGROUND: We did a randomised controlled trial to assess the benefit of
      maintenance infliximab therapy in patients with active Crohn's disease who
      respond to a single infusion of infliximab. METHODS: 573 patients with a score of
      at least 220 on the Crohn's disease activity index (CDAI) received a 5 mg/kg
      intravenous infusion of infliximab at week 0. After assessment of response at
      week 2, patients were randomly assigned repeat infusions of placebo at weeks 2
      and 6 and then every 8 weeks thereafter until week 46 (group I), repeat infusions
      of 5 mg/kg infliximab at the same timepoints (group II), or 5 mg/kg infliximab at
      weeks 2 and 6 followed by 10 mg/kg (group III). The prespecified co-primary
      endpoints were the proportion of patients who responded at week 2 and were in
      remission (CDAI <150) at week 30 and the time to loss of response up to week 54
      in patients who responded. Analyses of the co-primary endpoints were by intention
      to treat. FINDINGS: 335 (58%) patients responded to a single infusion of
      infliximab within 2 weeks. At week 30, 23 of 110 (21%) group I patients were in
      remission, compared with 44 of 113 (39%) group II (p=0.003) and 50 of 112 (45%)
      group III (p=0.0002) patients. Thus, patients in groups II and III combined were
      more likely to sustain clinical remission than patients in group I (odds ratio
      2.7, 95% CI 1.6-4.6). Throughout the 54-week trial, the median time to loss of
      response was 38 weeks (IQR 15 to >54) and more than 54 weeks (21 to >54) for
      groups II and III, respectively, compared with 19 weeks (10-45) for group I
      (p=0.002 and p=0.0002, respectively). Infliximab safety was consistent with that
      seen in other trials of infliximab in Crohn's disease and rheumatoid arthritis.
      In particular, the incidence of serious infections was similar across treatment
      groups. INTERPRETATION: Patients with Crohn's disease who respond to an initial
      dose of infliximab are more likely to be in remission at weeks 30 and 54, to
      discontinue corticosteroids, and to maintain their response for a longer period
      of time, if infliximab treatment is maintained every 8 weeks.

PMID- 12047963
TI  - Pentoxifylline for treatment of venous leg ulcers: a systematic review.
AB  - INTRODUCTION: Venous ulcers are usually treated with compression therapy, but,
      because this treatment may not be effective for some people, adjuvant therapy
      could be beneficial. We did a systematic review of randomised controlled trials
      that compared pentoxifylline (with and without compression treatment) with
      placebo, or other treatments, in patients with venous leg ulcers. METHODS: We
      identified eight trials (547 adults), five of which compared pentoxifylline and
      compression with placebo and compression (n=445), and three of which compared
      pentoxifylline alone with placebo (102). Our main aim was to determine whether
      pentoxifylline, with or without compression, was effective in treatment of venous
      leg ulcers. Analysis was by intention to treat. FINDINGS: Pentoxifylline was more
      effective than placebo in complete healing or substantial improvement of venous
      leg ulcers (relative risk 1.49, 95% CI 1.11-2.01). Pentoxifylline with
      compression was also more effective than placebo and compression in complete
      healing (1.30, 1.10-1.54). Patients taking pentoxifylline had no more adverse
      events than those on placebo (1.25, 0.87-1.80). The most frequent adverse event
      was mild gastrointestinal disturbance (43%). INTERPRETATION: Our results suggest
      that pentoxifylline gives additional benefit to compression for venous leg
      ulcers, and is possibly effective for patients not receiving compression.

PMID- 12047964
TI  - Comparison of survival, palliation, and quality of life with three chemotherapy
      regimens in metastatic colorectal cancer: a multicentre randomised trial.
AB  - BACKGROUND: This randomised trial compared three chemotherapy regimens in the
      first-line treatment of advanced colorectal cancer, in terms of their effect on
      overall and progression-free survival; other endpoints included toxicity, symptom
      palliation, and quality of life. METHODS: 905 patients were randomly assigned the
      de Gramont regimen (n=303; folinic acid 200 mg/m(2), fluorouracil bolus 400
      mg/m(2), and infusion 600 mg/m(2) on days 1 and 2, repeated every 14 days), the
      Lokich regimen (n=301; protracted venous infusion of fluorouracil 300 mg/m(2)
      daily), or raltitrexed (n=301; 3 mg/m(2) intravenously every 21 days). Analyses
      were by intention to treat. FINDINGS: Median follow-up of survivors was 67 weeks.
      For the de Gramont, Lokich, and raltitrexed groups, respectively, median survival
      was 294, 302, and 266 days. The hazard ratios for overall survival were 0.88 (95%
      CI 0.70-1.12, p=0.17) for de Gramont versus Lokich, and 0.99 (0.79-1.25, p=0.94)
      for de Gramont versus raltitrexed. An increase in treatment-related deaths was
      seen on raltitrexed (de Gramont one, Lokich two, raltitrexed 18) due to combined
      gastrointestinal and haematological toxicity. Patients' assessment of quality of
      life showed that raltitrexed was inferior to the fluorouracil-based regimens,
      especially in terms of palliation and functioning. INTERPRETATION: The deGramont
      and Lokich regimens were similar in terms of survival, quality of life, and
      response rates. The Lokich regimen was associated with more central line
      complications and hand-foot syndrome. Raltitrexed showed similar response rates
      and overall survival to the de Gramont regimen and was easier to administer, but
      resulted in greater toxicity and inferior quality of life.

PMID- 12047965
TI  - Ischaemic ulcer from a chemical burn.

PMID- 12047966
TI  - First 5 years of measles elimination in southern Africa: 1996-2000.
AB  - BACKGROUND: Measles is the leading cause of vaccine-preventable death in Africa.
      Regional measles elimination is considered feasible using current vaccines and a
      series of WHO-recommended strategies. We aimed to interrupt transmission of
      measles, and to use case-based surveillance to show the effect of such
      interruption. METHODS: In southern Africa from 1996, seven countries with a total
      population of approximately 70 million and with relatively high routine
      vaccination coverage implemented measles elimination strategies. In addition to
      routine measles immunisation at 9 months of age, these included nationwide catch
      up campaigns among children aged 9 months to 14 years, then follow-up campaigns
      every 3-4 years among children aged 9-59 months, and the establishment of case
      based measles surveillance with serological diagnostic confirmation. RESULTS:
      Nearly 24 million children aged 9 months to 14 years were vaccinated, with
      overall vaccination coverage of 91%. Reported clinical measles cases declined
      from 60000 in 1996 to 117 laboratory-confirmed measles cases in 2000. Reported
      measles deaths declined from 166 in 1996 to zero in 2000. No increase in adverse
      events was noted after the measles vaccination campaign. CONCLUSION: A reduction
      in measles mortality and morbidity can be achieved in very low-income countries,
      in countries that split their vaccination campaigns by geographical area or by
      age-group of the target population, and where initial routine measles vaccination
      coverage among infants was <90%, even when prevalence of HIV/AIDS was extremely
      high. Continued high-level national commitment will be crucial to implementation
      and maintenance of proven strategies in southern Africa.

PMID- 12047967
TI  - MBL genotype and risk of invasive pneumococcal disease: a case-control study.
AB  - BACKGROUND: Streptococcus pneumoniae is a major cause of morbidity and mortality
      in developed and developing countries. No common genetic determinants of
      susceptibility have been defined. Mannose-binding lectin (MBL) is a key mediator
      of innate host immunity that activates the complement pathway and directly
      opsonises some infectious pathogens. Mutations in three codons in the MBL gene
      have been identified, and individuals homozygous for a mutant genotype have very
      little or no serum MBL. We did a case-control study in the UK to assess whether
      these mutant genotypes were associated with invasive pneumococcal disease.
      METHODS: The frequencies of genotypes defined by the three mutations in codons
      52, 54, and 57, and a functional promoter polymorphism at -221, were compared in
      a two-stage study of 337 patients with invasive pneumococcal disease and 1032
      controls. All individuals were recruited from an ethnically homogeneous white
      population in Oxfordshire, UK. Patients had S pneumoniae isolated from a normally
      sterile site. FINDINGS: In our initial set of participants, 28 (12%) of 229
      patients and 18 (5%) of 353 controls were homozygotes for MBL codon variants
      (odds ratio 2.59 [95% CI 1.39-4.83], p=0.002). Neither heterozygosity for these
      codon variants nor the promoter polymorphism was associated with susceptibility.
      In a confirmatory study, 11 (10%) of 108 patients were MBL homozygotes compared
      with 36 (5%) of 679 controls (p=0.046). INTERPRETATION: Homozygotes for MBL codon
      variants, who represent about 5% of north Europeans and north Americans and
      larger proportions of populations in many developing countries, could be at
      substantially increased risk of invasive pneumococcal disease.

PMID- 12047968
TI  - Phosphine poisoning in a German office.

PMID- 12047969
TI  - Proteinuria and prenatal diagnosis of congenital nephrosis in fetal carriers of
      nephrin gene mutations.
AB  - High concentrations of alpha-fetoprotein (AFP) are used for prenatal diagnosis of
      the Finnish type of congenital nephrotic syndrome (NPHS1). We investigated the
      validity of this test. We retrospectively established fetal NPHS1 genotype and
      assessed renal pathology in 21 pregnancies that had been terminated because of
      raised concentrations of AFP in amniotic fluid. 12 fetuses were homozygous and
      nine were heterozygous (carriers) for NPHS1 mutations. Raised concentrations of
      AFP and similar proteinuric features in fetal kidneys were seen in both groups,
      indicating that these signs are unreliable for prenatal diagnosis of congenital
      nephrosis. We strongly recommend the use of mutation analysis of the NPHS1 gene
      to confirm the AFP results in prenatal diagnosis of NPHS1.

PMID- 12047970
TI  - Treatment of hypereosinophilic syndrome with imatinib mesilate.
AB  - Patients with hypereosinophilic syndrome show persistent eosinophilia without
      recognised cause. We treated five such patients with 100 mg imatinib mesilate
      (formerly STI-571) daily; four male patients with normal serum interleukin 5
      showed complete haematological responses; a female patient who did not respond
      had raised serum interleukin-5 concentrations. One patient developed leucopenia
      after 4 days of treatment; counts returned to normal when treatment was stopped.
      After 1 month, eosinophilia recurred; with further treatment for 2 days,
      eosinophil counts again became normal. All patients who responded stopped other
      treatments and reduced imatinib mesilate to 200 mg per week. This drug
      effectively controls eosinophilia in patients with hypereosinophilic syndrome and
      normal interleukin-5 concentrations.

PMID- 12047971
TI  - Diagnosis of susceptibility to malignant hyperthermia by use of a metabolic test.
AB  - Susceptibility to malignant hyperthermia is diagnosed by contracture test, which
      requires an open muscle biopsy sample. We postulated that intramuscular injection
      of caffeine increases local carbon dioxide pressure (pCO(2)) in individuals
      susceptible to malignant hyperthermia but not in those who are non-susceptible or
      in healthy individuals. We measured pCO(2) in the rectus femoris muscle during
      local stimulation with 500 microL caffeine 80 mmol/L in 12 patients susceptible
      to malignant hyperthermia, eight non-susceptible individuals, and seven healthy
      controls. In susceptible individuals, pCO(2) temporarily increased to a maximum
      of 63 mm Hg (IQR 61-69) compared with 44 mm Hg (43-47) in non-susceptible
      participants (p=0.003) and 42 mm Hg (41-46) in controls (p=0.003). There were no
      systemic side-effects. Metabolic monitoring of the highly diffusible CO(2)
      stimulated by caffeine might allow a minimally invasive test for susceptibility
      to malignant hyperthermia.

PMID- 12047972
TI  - Global Fund makes historic first round of payments.

PMID- 12047976
TI  - Is there an infectious component behind headaches and SIDS?

PMID- 12047977
TI  - US Senate weighs proposal on medical privacy.

PMID- 12047979
TI  - Australian court rules against tobacco company in lung-cancer case.

PMID- 12047980
TI  - Canadian spending on prescription drugs is increasing.

PMID- 12047981
TI  - India's new health policy aims to increase public investments.

PMID- 12047982
TI  - Europe and Africa forge new alliance against poverty-related disease.

PMID- 12047983
TI  - Treatment interventions for Parkinson's disease: an evidence based assessment.
AB  - We did a systematic review, with a uniform method of assessment of efficacy and
      safety, to assess the different interventions available for the management of
      Parkinson's disease (drugs, surgical interventions, and physical treatments) with
      respect to the following indications: prevention of disease progression,
      symptomatic treatment of motor features (parkinsonism), symptomatic control of
      motor complications, prevention of motor complications, and symptomatic treatment
      of non-motor features. Our aim was not to define practice guidelines, but rather
      to improve clinicians' knowledge of the presently available published clinical
      evidence, based mainly on randomised controlled trials. We hope that our review
      will help doctors to incorporate this background into their own decision-making
      strategy to make appropriate choices with respect to the treatment of individual
      patients with Parkinson's disease.

PMID- 12047984
TI  - Bearing witness: ethics in domestic violence research.
AB  - Epidemiological research involving people has inherent risks. The Council for
      International Organization of Medical Sciences provides guidance on the ethical
      principles of epidemiological research, including respect for people, non
      maleficence, beneficience, and justice. In this article we discuss the challenges
      of applying each principle to population research on domestic violence, an issue
      in which poorly designed research could put women in violent relationships at
      substantial risk. Main concerns include ensuring safety of respondents in a
      context in which many live with their abuser, protecting confidentiality when
      breaches could provoke an attack, and ensuring the interview process is affirming
      and does not cause distress. The inherent risks entailed in research can only be
      justified if the interview is used to provide information on available services
      and is a source of immediate referral when necessary, if high-quality data are
      obtained, and if findings are used to raise awareness of, and improve services
      for, women who experience domestic violence.

PMID- 12047985
TI  - A slice of bread.

PMID- 12047986
TI  - WHO: the casualties and compromises of renewal.
AB  - The World Health Organization is the leading international agency in health.
      WHO's reputation reached a peak in the 1970s with the then director-general
      Halfdan Mahler's advocacy of Health for All by the Year 2000 and the successful
      worldwide eradication of smallpox. The 1980s and 1990s saw WHO lose much of its
      authority. Too easily, the blame was put on one man-Mahler's successor, Hiroshi
      Nakajima. In 1998, Gro Harlem Brundtland, Figure 1 a former Prime Minister of
      Norway, took office and WHO began a period of major strategic and structural
      reform. Almost 4 years into her first term as director-general, I visited WHO's
      headquarters in Geneva to learn about Dr Brundtland's successes and failures.
      Figure 2 The ground rules of my visit were that I could talk with anybody and
      attend almost any meeting (budget discussions were excluded). I interviewed Dr
      Brundtland, executive directors, members of the staff association, and directors
      and project managers of programmes such as StopTB, Roll Back Malaria, HIV-AIDS,
      violence prevention, polio eradication, essential drugs and medicines, and
      sustainable development. At senior levels, WHO is confident and clear about its
      purpose-in a way that matches Mahler's vision and goes beyond it in results.
      Brundtland told me that her most important achievements were to have
      "strengthened the credibility of WHO" and to have "raised the awareness of health
      on to the political and global development agendas". But there is a troubling
      schism between the aspirations of its leadership and the realities faced by the
      organisation on the ground. Rapid change during the past 4 years has
      reinvigorated WHO's mandate, but poor management has created new tensions that
      the organisation's leadership seems unwilling to address.

PMID- 12047987
TI  - Hepatic pseudocapillarisation and atherosclerosis in ageing.
AB  - Cardiovascular disease secondary to atherosclerosis is the main cause of death
      and disability in industrialised countries, and ageing is the foremost risk
      factor for atherosclerosis. We present a hypothesis linking age-specific
      structural change in the liver with accepted pathogenic mechanisms leading to
      atherosclerosis. Ageing in the liver is associated with pseudocapillarisation of
      the sinusoidal endothelium, which is characterised by thickening of endothelium,
      basement membrane formation, and defenestration (loss of pores). Fenestrations
      (pores) normally form a liver sieve that allows passage of chylomicron remnants
      for subsequent uptake and metabolism by hepatocytes. Ageing is associated with
      impaired clearance of chylomicron remnants, postprandial hypertriglyceridaemia,
      and hence, atherosclerosis, which we propose is linked directly to loss of
      permeability of the liver sieve because of defenestration associated with
      pseudocapillarisation. Development of methods to maintain fenestrations of
      sinusoidal endothelium or to facilitate refenestration might be a new therapeutic
      strategy for management of cardiovascular disease in old people.

PMID- 12047988
TI  - Effects of MDMA (ecstasy) use and abstention on serotonin neurons.

PMID- 12047989
TI  - Effects of MDMA (ecstasy) use and abstention on serotonin neurons.

PMID- 12047992
TI  - IOU surgery and obese patients.

PMID- 12047990
TI  - Effects of MDMA (ecstasy) use and abstention on serotonin neurons.

PMID- 12047993
TI  - Depression and outcome after coronary artery bypass surgery.

PMID- 12047995
TI  - HIV-1 and tuberculosis infection.

PMID- 12047997
TI  - Asymmetrical dimethylarginine and risk of acute coronary events.

PMID- 12047998
TI  - Improvement of neonatal care and child survival in developing countries.

PMID- 12047999
TI  - The cloning debate and the cycle of evolution.

PMID- 12048000
TI  - Epidemiology and profit for pharmaceutical companies.

PMID- 12048001
TI  - Global fund for AIDS, tuberculosis and malaria.

PMID- 12048002
TI  - Are we promoting health?

PMID- 12048004
TI  - The spleen.

PMID- 12048015
TI  - Crinum L. (Amaryllidaceae).
AB  - Alkaloids isolated from Crinum species have been reviewed for the period 1985
      2000. Non-nitrogenous compounds have been surveyed for the first time. Botanical
      classification and biological activity are discussed. Spectral data literature
      sources are listed.

PMID- 12048016
TI  - Glucosinolates of seven medicinal plants from Thailand.
AB  - Nasturtium montanum was shown to contain glucobrassicin, 9-methylthionyl
      glucosinolate, oct-7-enyl glucosinolate, non-7-enyl glucosinolate, dec-7-enyl
      glucosinolate, methylsulfonyloctyl glucosinolate, methylsulfonylnonyl
      glucosinolate, methylsulfonyldecyl glucosinolate, benzyl glucosinolate, and
      Cleome chelidonii contained glucocapparin and glucocleomin. Raphanus sativus
      contained sulforaphene, plus sulforaphane, glucodehydroerucin, and gluconapin;
      Lepidum sativum contained benzyl glucosinolate and glucotropaeolin; Eruca
      versicaria contained glucoerucin; Cleome viscosa contained glucocapparin and
      glucocleomin, while Gynandropsis gynandra contained glucocapparin.

PMID- 12048017
TI  - Ethnopharmacy of the ethnic Albanians (Arbereshe) of northern Basilicata, Italy.
AB  - Intercultural studies about the methods of use and perceptions of traditional
      remedies in Europe are strategically important in understanding how
      pharmaceutical means in our multicultural modern societies are differently
      accepted by diverse ethnic groups. In this survey, we analysed the biological
      means traditionally used in the ethnomedicine of three Arbereshe (ethnic
      Albanians) communities in the Vulture area (northern Lucania, southern Italy).
      The majority of remedies are represented by plants belonging to 54 botanical
      taxa. A few of the recorded species have a traditional therapeutic use that has
      never previously been reported in southern Italy. Other means-especially used in
      the past-are comprised of mineral, animal and industrial derived materials. In
      specific cases, some of these materials and even plants are neither applied
      externally or internally, but are instead utilised as symbolic ritual objects in
      spiritual healing ceremonies. Ethnopharmacological and anthropological
      considerations about these usages are discussed.

PMID- 12048018
TI  - Preliminary evaluation of cytotoxic properties of Laurus nobilis leaf extracts.
AB  - n-Hexane, ethanol and water extracts of Laurus nobilis L. leaves were evaluated
      for cytotoxic properties using the Brine shrimp bioassay. Only the n-hexane
      extract exhibited cytotoxic activity.

PMID- 12048019
TI  - Antibacterial properties of Thymus pubescens and Thymus serpyllum essential oils.
AB  - Antibacterial properties of essential oils of Thymus pubescens and Thymus
      serpyllum collected at pre and flowering stages were studied. The oils were found
      to possess bactericidal activities.

PMID- 12048020
TI  - Antibacterial activity of Hygrophila stricta and Peperomia pellucida.
AB  - The crude methanolic extracts of Hygrophila scricta and Peperomia pellucida were
      fractionated into petrol, dichloromethane, ethyl acetate and butanol. All the
      crude extracts and the fractions exhibited a very good level of broad spectrum
      antibacterial activity. The fractions were more active than the crude extracts.
      The petrol fraction of H. stricta and the butanol fraction of P. pellucida were
      particularly good. No activity was noticed for the moulds tested.

PMID- 12048021
TI  - Antibacterial, antifungal activities of Barringtonia asiatica.
AB  - The crude methanolic extract of Barringtonia asiatica (leaves, fruits, seeds,
      stem and root barks) and the fractions (petrol, dichloromethane, ethyl acetate,
      butanol) exhibited a very good level of broad spectrum antibacterial activity. A
      number of fractions demonstrated antifungal activity against a number of fungi.

PMID- 12048022
TI  - Antifungal activity of the volatile oil of Eucalyptus citriodora.
AB  - The volatile oil extracted from the leaves of Eucalyptus citriodora showed a wide
      spectrum of antifungal activity.

PMID- 12048023
TI  - Organic carbonate from Calotropis procera leaves.
AB  - The leaves of Calotropis procera yielded an organic carbonate (1), along with
      stigmasterol and beta-sitosterol, identified by spectroscopic methods.

PMID- 12048024
TI  - Arteminin, a new coumarin from Artemisia apiacea.
AB  - The isolation of 6,7-dimethoxycoumarin (1), 6-methoxy-7,8-methylenedioxycoumarin
      (2), 5,6-dimethoxy-7,8-methylenedioxycoumarin (3), 6-hydroxy-7,8
      methylenedioxycoumarin (4) and 5-hydroxy-6,8-dimethoxycoumarin (arteminin) (5) is
      reported.

PMID- 12048026
TI  - Ginkgo biloba L.

PMID- 12048025
TI  - Constituents of aromatic plants: eucalyptol.
AB  - The subacute toxicity studies reported up to now in rats and mice suggested that
      mice were less susceptible than rats to the toxicity of eucalyptol. In fact,
      after gavage, it was found toxic in male rats at doses higher than 600 mg/kg
      while no effect was seen in mice up to 1200 mg/kg. However, the limitations and
      the quality of the study do not allow the extrapolation of a 'no effect level'.
      Several reports in rat and brushtail possum show the formation of hydroxylated
      bicycled products of eucalyptol as main metabolites. Moreover, metabolites which
      require ring opening have been also detected. Following the accidental exposure
      of human beings, death was reported in two cases after ingestion of 3.5-5 ml of
      essential eucalyptus oil, but a number of recoveries have also been described for
      much higher amounts of oil.

PMID- 12048027
TI  - Expression variance, biochemical and immunological properties of Toxoplasma
      gondii dense granule protein GRA7.
AB  - During intracellular stay, Toxoplasma gondii secretes dense granule proteins
      (GRA) which remodel the parasitophorous vacuole and are considered functional in
      parasite-host interrelation. Comparative analysis of parasites from mouse
      virulent strain BK and an in vitro attenuated variant revealed that the level of
      GRA7 expression correlates with T. gondii virulence: proteome analysis and
      quantitation by immunoblot demonstrated a massive decrease in GRA7 steady-state
      synthesis parallel to the loss of virulence. Properties of GRA7 that are
      pertinent to its membrane targeting and to GRA7-directed immune resistance were
      studied in detail. GRA7 is exclusively membrane-associated in both parasites and
      infected host cells as demonstrated by subcellular fractionations. Triton X-114
      partitioning of isolated parasites substantiated that GRA7 is an integral
      membrane protein, the hydrophobic stretch from amino acid 181 to 202 providing a
      possible membrane anchor. A fraction enriched for membranous material from
      infected host cells contained additional forms of GRA7 with reduced mobility in
      gel electrophoresis, indicating that the protein is modified after exocytosis
      from the parasite. By flow cytometric analysis, GRA7 was detected on the surface
      of intact host cells. An intracellular origin of surface-associated GRA7 seems
      likely since GRA7 released from extracellular parasites failed to label the host
      cell surface. Consistent with a role at a parasite-host interface, GRA7 proved to
      be a target antigen of the intracerebral immune response as evidenced by the
      presence of GRA7-specific antibodies in mouse cerebrospinal fluid during chronic
      infection.

PMID- 12048028
TI  - Mouse resident peritoneal macrophages partially control in vitro infection with
      Coxiella burnetii phase II.
AB  - Coxiella burnetii, the agent of Q fever in man and of coxiellosis in other
      species, is a small, dimorphic, obligate intracellular bacterium, sheltered
      within large, acidified, and hydrolase-rich phagosomes. Although several primary
      and established cell lines, macrophage-like cells, and primary macrophages from
      other species have been infected with C. burnetii, the infection of mouse primary
      macrophages has not been sufficiently characterized. In this report
      quantification of DAPI (4', 6-diamino-2-phenylindole) fluorescence images
      acquired by confocal microscopy, and transmission electron microscopy were used
      to compare the infection of three mouse-derived cells, L929 fibroblasts, J774
      macrophage-like cells, and resident peritoneal macrophages, with a phase II clone
      of C. burnetii known to be non-virulent for mammals. Infected peritoneal
      phagocytes differed from L929 or J774 cells in that: (a) large vacuoles took
      longer to appear (3-5 d instead of 2), and were only found in a subset (20-30%)
      of macrophages, as opposed to in more than 70% of the other cells; (b) total and
      vacuole-associated relative bacterial loads in L929 and J774 cells were several
      fold higher than in peritoneal macrophages; (c) estimated doubling times of the
      bacteria were about 68 h in the primary macrophages, 18 h in J774 and 22 h in
      L929 cells. Thus, mouse resident peritoneal macrophages control both the
      formation of the large vacuoles and the intracellular proliferation of C.
      burnetii phase II.

PMID- 12048029
TI  - Apoptosis during ectromelia orthopoxvirus infection is DEVDase dependent: in
      vitro and in vivo studies.
AB  - Ectromelia virus (EV), which causes mousepox, is a member of the orthopoxviruses
      that are defined as being able to suppress apoptosis. Caspase-3 is one of the key
      effector proteases which regulates the apoptotic cascade and which is responsible
      for DNA fragmentation observed during apoptosis. It is well known that viruses,
      especially poxviruses, can inhibit caspase activity. Here, we report that EV can
      regulate apoptosis in vitro, suppressing the activity of caspases recognizing the
      DEVD (Asp-Glu-Val-Asp) motif (caspase-3 and -7) before successful virus
      replication is completed. Caspase-3 activity measurement showed that an increase
      in caspase-3 activity preceded the peak of DNA fragmentation demonstrated by
      TUNEL staining of L929 and RK-13 cells. By using specific caspase inhibitors (Ac
      DEVD-CHO, Ac-IETD-CHO and zVAD-fmk), we showed that caspase-3 and -7 (DEVDases)
      are major effector caspases during EV-induced apoptosis in permissive L929 and RK
      13 cell cultures. Apoptosis in vivo seems to play an important role during
      viraemia as well as during the clearance of EV from genetically susceptible
      BALB/c (H-2(d)) mice. However, as shown by measurement of caspase-3 activity,
      caspase-3 protein detection and M30-antibody staining, both DEVDases seem to play
      an important role during EV clearance from draining lymph nodes and conjunctivae
      at 15 days p.i. up to 20 days p.i., whereas in the liver and spleen DNA
      fragmentation coexisted with viral multiplication and secondary viraemia.
      Apoptosis was DEVDase dependent only in the liver, while spleen DNA fragmentation
      observed between 5 and 10 days p.i. was caspase independent. Therefore, we
      conclude that DEVDase- (caspase-3- and caspase-7-) dependent apoptosis is an
      important mechanism regulating the resolution of EV infection.

PMID- 12048030
TI  - Antibiotic resistance and virulence properties of Pseudomonas aeruginosa strains
      from mechanically ventilated patients with pneumonia in intensive care units:
      comparison with imipenem-resistant extra-respiratory tract isolates from
      uninfected patients.
AB  - We investigated the epidemiology of antibiotic resistance and virulence
      properties among Pseudomonas aeruginosa clinical isolates collected in 1999 from
      patients hospitalized in the intensive care units of the centre hospitalier
      d'Orleans, in France. We compared the totality of the strains from mechanically
      ventilated patients with pneumonia (33 non-duplicate isolates, group 1) to 15
      randomly chosen, imipenem-resistant, extra-respiratory tract isolates, collected
      from non-infected patients hospitalized in the same units (group 2). The isolates
      were serotyped, typed by random amplified polymorphic DNA (RAPD), and screened
      for their pneumocyte cell adherence, cytotoxicity, and antibiotic resistance. A
      total of 35 RAPD profiles were found, and only two profiles were encountered in
      both groups, demonstrating a high genetic diversity. 84.8% of the group 1 and
      93.3% of the group 2 isolates adhered to A549 cells. Three non-exclusive adhesive
      patterns were observed: a diffuse adhesion in 38 isolates, a localized adhesion
      in 14 isolates, and an aggregative adhesion in seven isolates. 78.8% of the group
      1 and 93.3% of the group 2 isolates were cytotoxic. Considering all 48 isolates,
      there was a strong and statistically significant correlation between cytotoxicity
      and adherence. Among the three dominant serotypes, O:12 isolates were in majority
      avirulent, but the great majority of O:1 and all the O:11 isolates were found
      adherent and cytotoxic. Gentamicin was the least active antibiotic for both
      groups, and ceftazidime was the most active antibiotic for group 1 and amikacin
      for group 2. The penicillinase production phenotype was significantly correlated
      with a decrease in P. aeruginosa virulence.

PMID- 12048031
TI  - Subtle mutations in the cysteine region of HIV-1 Vif drastically alter the viral
      replication phenotype.
AB  - Mutations were introduced into the region encoding the two cysteine and nearby
      amino acid residues of human immunodeficiency virus type 1 (HIV-1) Vif protein
      and, 12 single-amino-acid viral mutants were constructed. Determination of their
      growth characteristics in two lymphocytic cell lines revealed that only a single
      amino acid change in the cysteine region greatly altered the replication
      phenotype. In particular, the four mutants of amino acid 132 of Vif were grouped
      into three categories on the basis of their growth potentials. These results
      indicate that the cysteine region of Vif is critical for the cell-dependent
      replication efficiency of HIV-1.

PMID- 12048032
TI  - Mechanisms of immunity against rickettsiae. New perspectives and opportunities
      offered by unusual intracellular parasites.
AB  - Investigation of the biology, pathology and immunology of rickettsial diseases
      offers new insights useful not only for the field of rickettsiology, but more
      importantly for the understanding of general principles of host-intracellular
      parasite relationships and, in particular, the immune interaction between
      endothelial cells and immune cells in the context of infection.

PMID- 12048033
TI  - Tuberculosis unleashed: the impact of human immunodeficiency virus infection on
      the host granulomatous response to Mycobacterium tuberculosis.
AB  - The granuloma plays a critical role in the host immune response to Mycobacterium
      tuberculosis, containing the organism and confining it in a latent state in most
      infected individuals. Indeed, approximately one-third of the world's population
      has latent M. tuberculosis infection. However, over the past decade, the human
      immunodeficiency virus type 1 (HIV-1) pandemic has profoundly affected the
      incidence and clinicopathological features of tuberculosis. This review examines
      the immunological mechanisms whereby HIV-1 impairs the establishment, maintenance
      and function of the tuberculous granuloma.

PMID- 12048034
TI  - Mechanisms of inhibition of the host interferon alpha/beta-mediated antiviral
      responses by viruses.
AB  - Complex multicellular organisms have evolved sophisticated mechanisms to prevent
      and control infection by pathogens. Among these mechanisms, the type I interferon
      or interferon alpha/beta system represents one of the first lines of defense
      against viral infections. Typically, viral infection induces the synthesis and
      secretion of interferon alpha/beta by the infected cell, which in turn activates
      signaling pathways leading to an antiviral state. As a counter measure, many
      viruses have developed intriguing mechanisms to evade the interferon alpha/beta
      system of the host. In this review, we will summarize recent research
      developments in this interesting field of virus-host cell interactions.

PMID- 12048035
TI  - Hepatitis E: an overview.
AB  - The hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded
      RNA virus with icosahedral symmetry. Although it is related to the alpha-virus
      superfamily, the HEV is classified as a separate Hepatitis E-like viruses genus.
      Infection in humans occurs in sporadic and epidemic forms and can cause an acute,
      self-limited, icteric hepatitis. Recent studies indicate the existence of a
      reservoir in animals.

PMID- 12048036
TI  - Humoral immune responses to microbial infections in the genital tract.
AB  - Human reproductive tracts represent components of the mucosal immune system with
      unique features. Although secretory IgA is present, IgG is more abundant, and
      typical mucosa-associated lymphoid tissue for generating common mucosal immune
      responses is absent. Antibody responses to genital infections or to locally
      applied vaccines are usually modest, but alternative strategies for eliciting
      genital tract antibodies are being developed.

PMID- 12048037
TI  - Correlation between oral malodor and periodontal bacteria.
AB  - Volatile sulfur compounds (VSCs), including hydrogen sulfide, methyl mercaptan,
      and dimethyl sulfide, are primarily responsible for oral malodor. Recently, the
      mgl gene encoding L-methionine-alpha-deamino-gamma-mercaptomethane-lyase, which
      produces methyl mercaptan, was cloned from Porphyromonas gingivalis. This article
      discusses the mechanism and pathogenic role of the formation of VSCs by oral
      bacteria.

PMID- 12048038
TI  - Brain-computer interfaces for communication and control.
AB  - For many years people have speculated that electroencephalographic activity or
      other electrophysiological measures of brain function might provide a new non
      muscular channel for sending messages and commands to the external world - a
      brain-computer interface (BCI). Over the past 15 years, productive BCI research
      programs have arisen. Encouraged by new understanding of brain function, by the
      advent of powerful low-cost computer equipment, and by growing recognition of the
      needs and potentials of people with disabilities, these programs concentrate on
      developing new augmentative communication and control technology for those with
      severe neuromuscular disorders, such as amyotrophic lateral sclerosis, brainstem
      stroke, and spinal cord injury. The immediate goal is to provide these users, who
      may be completely paralyzed, or 'locked in', with basic communication
      capabilities so that they can express their wishes to caregivers or even operate
      word processing programs or neuroprostheses. Present-day BCIs determine the
      intent of the user from a variety of different electrophysiological signals.
      These signals include slow cortical potentials, P300 potentials, and mu or beta
      rhythms recorded from the scalp, and cortical neuronal activity recorded by
      implanted electrodes. They are translated in real-time into commands that operate
      a computer display or other device. Successful operation requires that the user
      encode commands in these signals and that the BCI derive the commands from the
      signals. Thus, the user and the BCI system need to adapt to each other both
      initially and continually so as to ensure stable performance. Current BCIs have
      maximum information transfer rates up to 10-25bits/min. This limited capacity can
      be valuable for people whose severe disabilities prevent them from using
      conventional augmentative communication methods. At the same time, many possible
      applications of BCI technology, such as neuroprosthesis control, may require
      higher information transfer rates. Future progress will depend on: recognition
      that BCI research and development is an interdisciplinary problem, involving
      neurobiology, psychology, engineering, mathematics, and computer science;
      identification of those signals, whether evoked potentials, spontaneous rhythms,
      or neuronal firing rates, that users are best able to control independent of
      activity in conventional motor output pathways; development of training methods
      for helping users to gain and maintain that control; delineation of the best
      algorithms for translating these signals into device commands; attention to the
      identification and elimination of artifacts such as electromyographic and electro
      oculographic activity; adoption of precise and objective procedures for
      evaluating BCI performance; recognition of the need for long-term as well as
      short-term assessment of BCI performance; identification of appropriate BCI
      applications and appropriate matching of applications and users; and attention to
      factors that affect user acceptance of augmentative technology, including ease of
      use, cosmesis, and provision of those communication and control capacities that
      are most important to the user. Development of BCI technology will also benefit
      from greater emphasis on peer-reviewed research publications and avoidance of the
      hyperbolic and often misleading media attention that tends to generate
      unrealistic expectations in the public and skepticism in other researchers. With
      adequate recognition and effective engagement of all these issues, BCI systems
      could eventually provide an important new communication and control option for
      those with motor disabilities and might also give those without disabilities a
      supplementary control channel or a control channel useful in special
      circumstances.

PMID- 12048039
TI  - Neurophysiological correlate of clinical signs in Parkinson's disease.
AB  - Clinical diagnosis of Parkinson's disease (PD) is not always coincident with
      pathological findings. A better characterization of the disease from the results
      of studies in various areas of neuroscience can help in improving the rate of
      diagnostic certainty. Neurophysiology is among the techniques with better chances
      to furnish specific diagnostic cues on motor aspects of the disease.
      Neurophysiology provides quantifiable data using non-invasive, relatively
      inexpensive, methods. Neurophysiological tests can be applied with no previous
      preparation, and repeated many times without dangerous consequences. To be
      rewarding, however, neurophysiological examination should be done in close
      cooperation between the clinician who detects relevant specific signs, and the
      neurophysiologist who devises the most demonstrative methods to document those
      signs. In this review, we describe the neurophysiological correlate of symptoms
      and signs in patients with PD, and particularly their pathophysiological meaning,
      with special focus on those that could be more helpful to the neurologists in
      establishing differences with respect to other diseases presenting with
      parkinsonism.

PMID- 12048040
TI  - Task-related EEG and ERP changes without performance impairment following a
      single dose of phenytoin.
AB  - OBJECTIVES: The acute effects of a single, low dose of phenytoin on behavioral
      and neurophysiological measures of cognitive function were examined in healthy
      adults. METHODS: Electroencephalograms (EEGs) were recorded from 7 healthy
      volunteers while they performed spatial working memory tasks and while they
      rested quietly. Behavioral measures, EEG power spectra, and event-related
      potentials (ERPs) were compared between separate sessions in which subjects
      ingested either 10mg/kg of phenytoin or placebo. RESULTS: Peak serum levels of
      phenytoin were in the low therapeutic range. Although participants reported
      subjective effects of the drug, task accuracy and response time were not
      affected. In the resting EEG, phenytoin decreased power in the alpha band. In the
      task-related EEG, the frontal midline theta signal was enhanced in response to
      increased task difficulty following placebo but not following phenytoin. An
      attention-related augmentation of the N160 ERP to matching stimuli was also
      reduced by phenytoin. CONCLUSIONS: Neurophysiological measures displayed
      sensitivity to subtle alterations in attentional processing even in response to a
      dose of phenytoin too low to produce behavioral impairment. Such results indicate
      that EEG and ERP measures can provide information about the neurocognitive side
      effects of medications that cannot be inferred from cognitive task performance
      measures alone.

PMID- 12048041
TI  - Assessing cerebral dysfunction with probe-evoked potentials in a CNV task -- a
      study in alcoholics.
AB  - OBJECTIVES: Contrary to event-related potential (ERP) components N1, N2 and P3,
      slow ERPs have rarely been used in assessing cerebral dysfunction in mental
      disorders. Focussing on slow waves (SWs) and on patients with mild cerebral
      dysfunction, we recorded ERPs in alcoholics using a dual task design. METHODS:
      ERPs to auditory probes presented either 1s before the warning or 1s before the
      imperative stimulus of a visual contingent negative variation (CNV) paradigm were
      recorded from 33 scalp electrodes in 27 alcoholics following detoxification and
      12 healthy controls. Independent component analysis (ICA) was used to separate
      potentially overlapping spatial components. RESULTS: In alcoholics compared to
      controls, probe ERPs showed increased N2, decreased P3 and increased negative SWs
      of two types appearing pre- and post-P3, respectively. Both negative SWs
      significantly correlated with neuropsychological indices reflecting verbal
      intelligence and memory functions. The increase in probe-evoked N1 and P3
      potentials during CNV, putatively associated with enhanced cortical excitability,
      significantly correlated with clinical features of protracted alcohol withdrawal
      syndrome in alcoholics. CONCLUSIONS: Our experimental approach revealed two types
      of negative SWs which strongly correlated with neuropsychological deficits of
      mildly impaired patients. It is suggested that our methods might enhance
      diagnostic efficiency of ERPs. An electrophysiological measure of protracted
      alcohol withdrawal might be useful for managing central nervous system
      dysfunction in alcoholics.

PMID- 12048042
TI  - Probability interrelations between pre-/post-stimulus intervals and ERD/ERS
      during a memory task.
AB  - OBJECTIVES: To investigate the functional relationship between oscillatory
      electroencephalographic (EEG) components (pre-/post-stimulus intervals) with
      audio-event-related desynchronization/synchronization (ERD/ERS). METHODS: In an
      experimental study (9 subjects), the probability-classification analysis of
      single-trial spectral EEG changes was utilized. Results were compared with
      auditory ERD/ERS. RESULTS: It was shown that (1) variability of EEG spectral
      patterns was considerable, (2) EEG activity was different at various task stages,
      (3) probability measures were different from the results of conventional
      frequency analysis, (4) probability of trials with alpha- and theta-patterns was
      characteristically different in various task stages, (5) the occurrence of alpha-
      and theta-trials were most probable, but not frequent enough to characterize all
      the trials. The results suggest that the ERD/ERS responses are influenced by EEG
      characteristics in the pre-stimulus interval, which also have a strong influence
      on the EEG in the post-stimulus interval. CONCLUSIONS: Alpha- and theta-ERD/ERS
      responses during memory task performance are not typical for all trials. They
      reflect EEG changes only in approximately 39% for alpha-activity and
      approximately 43% for theta-oscillations of all trials, what reflects piecewise
      stationary EEG structure.

PMID- 12048043
TI  - The costs of freedom: an ERP -- study of non-canonical sentences.
AB  - OBJECTIVES: The present investigation explored the electrophysiological
      correlates of working memory during sentence comprehension. METHODS: Event
      related brain potentials (ERP) were recorded from 29 channels in 22 subjects,
      while they read German sentences having subject-first (canonical) or object-first
      (non-canonical) word orders. RESULTS: Three different ERP effects were observed:
      a negativity (maximum at Fc5) differentiating unambiguous object-first and
      subject-first sentences, interpreted as reflecting the demands of the object
      first sentences on working memory; a second negativity (maximum at F7) to the
      subject noun-phrase in object-first sentences, interpreted as indicating
      retrieval of verbal material. Finally, a parietal positivity was found for
      ambiguous sentences that turned out to have a non-canonical word order, which was
      interpreted as indicating revision and reevaluation processes. CONCLUSIONS: The
      present data underscore the different roles of working memory in comprehension.

PMID- 12048044
TI  - Visual and auditory event-related potentials in sporadic amyotrophic lateral
      sclerosis.
AB  - OBJECTIVES: To investigate the relationship between amyotrophic lateral sclerosis
      (ALS) and cognitive function by means of oddball event-related potentials (ERPs)
      and to determine the usefulness of this methodology in the cognitive status
      assessment of physically disabled patients. METHODS: Visual and auditory oddball
      ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive
      battery of neuropsychological (NP) tests assessed intelligence, executive
      functions, attention, memory, word fluency, visuo-motor and visual-constructive
      skills. RESULTS: All patients performed visual and auditory ERPs and 75% of cases
      showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the
      entire psychometric evaluation with significant impairment on tests of executive
      function and attention. A significant correlation between delayed visual (P<0.04)
      and auditory (P<0.04) P300 latency and impaired NP tests was found. CONCLUSIONS:
      In agreement with literature data, our findings confirm the hypothesis of
      cognitive impairment in ALS patients especially on attention and executive
      functions suggesting a more extensive degeneration beyond the motor areas. ALS
      causes severe physical disabilities and such a condition may interfere with NP
      testing. Thus, the P300 seems to be a useful tool for the assessment of cognition
      and attention when severe physical deficits are present.

PMID- 12048045
TI  - Electric brain responses to inappropriate harmonies during listening to
      expressive music.
AB  - OBJECTIVES: Recent studies with event-related brain potentials (ERPs)
      investigating music processing found (early) negativities with right-hemispheric
      predominance as a response to inappropriate harmonies within sequences of chords.
      The stimuli used in those studies were fairly artificial in order to control the
      experimental factors (e.g. variations in tempo and loudness were eliminated).
      This raises the question of whether these ERPs can also be elicited during
      listening to more naturalistic stimuli. METHODS: Excerpts from classical piano
      sonatas were taken from commercial CDs and presented to the participants while
      recording the continuous electroencephalogram. Expected chords and unexpected
      (transposed) chords were presented at the end of chord-sequences. RESULTS:
      Unexpected chords elicited a negativity which was maximal around 250 ms, visible
      over both hemispheres, and preponderant over right temporal leads. CONCLUSIONS:
      The found negativity is strongly reminiscent to both early right anterior
      negativity and right anterior-temporal negativity, suggesting that cognitive
      processes underlying these ERP components are not only elicited with fairly
      artificial experimental stimuli but also when listening to expressive music.

PMID- 12048046
TI  - Maturation of cortical sound processing as indexed by event-related potentials.
AB  - OBJECTIVES: Children's auditory event-related potentials (ERPs) are dominated by
      the P1 and N2 peaks, while the N1 wave emerges between 3 and 4 years of age. The
      neural substrates and the behavioral correlates of the protracted N1 maturation,
      as well as of the 10-year long predominance of the N2 are unclear. The present
      study utilized high-resolution electroencephalography to study the maturation of
      auditory ERPs from age 4 to adulthood and to compare the sources of the N1 and
      the N2 peaks in 9-year-old children and adults. METHODS: Three partial harmonic
      tones were delivered with short (700 ms) and long (mean of 5s) stimulus onset
      asynchrony (SOA), with only 700 ms SOA used with 4-year-olds. RESULTS: With a
      short SOA, 4- and 9-year-old children displayed P1 and N2 peaks, whereas adults
      showed P1, N1, P2, and N2 waves. With a long SOA, 9-year-olds also displayed an
      N1 peak, which was frontal in scalp distribution to that in adults who showed P1,
      N1, and P2 peaks. After filtering out the slow N2 activity, the N1 wave was also
      revealed in the short-SOA data in 9-year-old but not in 4-year-old children. In
      adults and in 9-year-olds, the neural sources of the N2 and N1 mapped onto the
      superior aspects of the temporal lobes, the sources of the N2 being anterior to
      those of the N1. CONCLUSIONS: The results indicated that children's N1 is
      composed of differently weighted components as that in adults, and that in both
      children and adults the N1 and N2 are generated by anatomically distinct
      generators. A protracted ontogeny of the N1 could be linked with that of auditory
      sensitivity and orienting, whereas the P1 and N2 peaks are suggested to reflect
      auditory sensory processes.

PMID- 12048047
TI  - Time-dependent variation in cerebral and autonomic activity during periodic leg
      movements in sleep: implications for arousal mechanisms.
AB  - OBJECTIVES: A hierarchy in arousal response has been proposed for spontaneous
      arousal by analyzing the temporal changes in heart rate (HR) and
      electroencephalographic (EEG) activity. To address the question as to whether the
      same continuum may be proposed in sleep disorders, we performed temporal spectral
      EEG and HR analyses during periodic leg movements (PLM) associated or not with
      microarousal (MA). METHODS: Data were obtained in 12 patients with restless leg
      syndrome and/or PLM syndrome. PLMs were classified into 3 types including PLM
      associated with MA, PLM without MA, and PLM associated with delta or K-complex
      bursts. HR and EEG spectral analyses were done for 10s before and 10s after the
      PLM onset. RESULTS: Each type of PLM was associated with a typical EEG and
      autonomic pattern consisting of an increase in HR and delta band activity before
      the PLM, regardless of the presence or absence of MA. Thereafter, a rise in
      delta, alpha and beta(2) activity was noted associated with tachycardia. This was
      greater when MA or bursts of slow wave activity were present. In the period
      following the PLM, HR, delta and alpha power showed a long-lasting decrease with
      values significantly below the baseline. CONCLUSIONS: From these data, we can
      conclude that: (1) cardiac and cerebral changes occur in association with PLM
      even when MA cannot be detected; (2) the combined increase in delta activity and
      HR before the onset of PLM suggests that these changes are part of the arousal
      response during PLM; (3) the graded arousal response during PLM confirms that the
      human arousal response involves a progression of central nervous system
      activation from brainstem to cortical level.

PMID- 12048048
TI  - Spontaneous sleep interruptions during extended nights. Relationships with NREM
      and REM sleep phases and effects on REM sleep regulation.
AB  - OBJECTIVES: There is no agreement in the literature as to whether sleep
      interruption causes rapid eye movement (REM) pressure to increase, and if so,
      whether this increase is expressed as shortened REM latency, increased REM
      density, or increased duration of REM sleep. The purpose of the present study was
      to examine the effect of different durations of spontaneous sleep interruptions
      on the regulation of REM sleep that occurs after return to sleep. METHODS: The
      occurrence of spontaneous periods of wakefulness and their effects on subsequent
      REM sleep periods were analysed in a total sample of 1189 sleep interruptions
      which occurred across 364 extended nights in 13 normal subjects. RESULTS:
      Compared with sleep interruptions that last less than 10 min, sleep interruptions
      that last longer than 10 min occur preferentially out of REM sleep. In both the
      short and long types of sleep interruptions, the duration of REM periods that
      ended in wakefulness were shorter than the duration of those that were not
      interrupted by wakefulness. REM densities of the REM periods that terminated in
      periods of wakefulness were higher than those of uninterrupted REM periods. The
      proportion of episodes of wakefulness following REM sleep that were long-lasting
      progressively increased over the course of the extended night period. The sleep
      episodes that followed the periods of wakefulness were characterised by a short
      REM latency. REM duration was increased in episodes that followed long sleep
      interruptions compared to those that followed short sleep interruptions. REM
      density did not appear to change significantly in the episodes that followed
      sleep interruption. CONCLUSIONS: REM sleep mechanisms appear to be the main force
      controlling sleep after a spontaneous sleep interruption, presumably because
      during the second half of the night, where more sleep interruptions occur, the
      pressure for non-rapid eye movement sleep is reduced and the circadian rhythm in
      REM sleep propensity reaches its peak. Processes promoting REM sleep at the end
      of the night are consistent with the Pittendrigh and Daan dual oscillator model
      of the circadian pacemaker.

PMID- 12048049
TI  - Age effects on visual EEG responses reveal distinct frontal alpha networks.
AB  - OBJECTIVES: The present study aimed to describe the effect of aging on single
      trial visual alpha responses. METHODS: Visual evoked potentials were recorded at
      F3, Cz, P3, and O1 in 12 young (20-30-year-olds) and in 10 middle-aged adults (50
      55-year-olds). Slow (7-10 Hz) and fast (10-15 Hz) alpha frequency bands were
      analyzed. Three parameters of single alpha responses were assessed for the 0-300
      ms period after stimulus: (i) maximal single-sweep amplitude; (ii) phase-locking
      with stimulus, and (iii) enhancement of post-stimulus relative to pre-stimulus
      alpha activity. RESULTS: Ongoing alpha activity at anterior sites was larger in
      middle-aged subjects. Age differences in response amplitude depended on the
      anterior shift of ongoing alpha activity. Over fronto-central areas, the phase
      locking of fast alpha responses was significantly increased, whereas the phase
      locking of slow alpha responses was decreased in middle-aged compared to young
      adults, independently of amplitude. In contrast to slow alpha responses, frontal
      and occipital fast alpha responses were interrelated. CONCLUSIONS: These
      observations are in accordance with previous findings from the auditory modality
      implying that the age-related changes in frontal alpha oscillations are modality
      independent. Slow and fast frontal alpha responses were affected differentially
      by the age, which might reflect the activations of functionally distinct alpha
      networks.

PMID- 12048050
TI  - Relative utility of sphenoidal and temporal surface electrodes for localization
      of ictal onset in temporal lobe epilepsy.
AB  - OBJECTIVES: To compare localization of ictal onsets in patients with possible
      temporal lobe epilepsy (TLE) using true temporal electrodes (TE), at positions T1
      and T2, and sphenoidal electrodes (SpE). METHODS: A total of 101 ictal tracings
      in 31 patients with possible TLE were independently reviewed by two readers and
      graded as meeting (TE+, SpE+) or not meeting (TE-, SpE-) strictly-defined mesial
      temporal onset criteria. TE and SpE were reviewed in separate montages, with ad
      lib adjustment of filters and sensitivity. Discrepancies between TE and SpE were
      noted, with inter-reader disagreements resolved by a third reviewer. RESULTS: All
      seizures scored as SpE+ were also scored as TE+, with one exception. The sole
      SpE+/TE- seizure did not add incremental useful information in that patient, who
      had other, similar seizures which were TE+. Five seizures in 4 patients were
      scored as TE+ and SpE-, most due malfunction of SpE prior to seizure onset. One
      of these seizures was scored TE+/SpE- in a patient believed to have neocortical
      epilepsy. CONCLUSIONS: In this series, SpE were unnecessary to detect seizures
      which meet strict mesial temporal onset criteria and did not yield useful
      information for surgical evaluation beyond that provided by TE. It remains
      unclear if SpE are more helpful than TE in distinguishing lateral from mesial
      ictal onset. Digital review of ictal tracings may resolve discrepancies between
      TE and SpE.

PMID- 12048052
TI  - High voltage electrical stimulation of the proximal hypoglossal nerve in normal
      subjects.
AB  - OBJECTIVES: It is often difficult to stimulate the proximal hypoglossal nerve by
      magnetic occipital stimulation, even in normal subjects. Therefore, we tested an
      improved method of stimulating the proximal hypoglossal nerve, using high voltage
      electrical stimulation. METHODS: The proximal hypoglossal nerve was activated by
      high voltage electrical stimulation using surface electrodes over the occipital
      skull. The compound muscle action potential (CMAP) was recorded from the lingual
      muscles using surface electrodes in 10 normal subjects. CMAP and F waves produced
      by distal hypoglossal nerve stimulation and motor evoked potentials produced by
      transcranial magnetic stimulation were also recorded. RESULTS: When the anode
      electrode was placed at the mastoid process and the cathode below the inion, the
      unilateral proximal hypoglossal nerve was readily stimulated supramaximally in
      all the subjects. The CMAP latency was the same as that obtained with magnetic
      occipital stimulation. The central motor conduction time (CMCT) calculated from
      the proximal CMAP was 4.1+/-0.4 ms in the contralateral corticobulbar tract and
      4.4+/-0.4 ms in the ipsilateral. The CMCT calculated from the minimal F wave
      latency was 3.3+/-0.2 ms. CONCLUSIONS: The high voltage electrical stimulation is
      a useful method for stimulating the proximal hypoglossal nerve to estimate the
      CMCT of the corticobulbar tract.

PMID- 12048051
TI  - Reproducibility of hemispheric blood flow increases during line bisectioning.
AB  - OBJECTIVES: To determine if attention-related changes of hemispheric perfusion
      increases, as assessed by blood-flow sensitive techniques, are as reliable as
      language-related hemispheric perfusion increases. METHODS: The reproducibility of
      hemispheric blood flow velocity increases during a line bisection task was
      assessed with functional transcranial Doppler sonography. RESULTS: Over repeated
      examinations, the index of lateralization of 20 healthy subjects showed a high
      test-retest reproducibility (r=0.9, P<0.01). No practice effects were detected
      over the course of 10 re-assessments of one subject. CONCLUSIONS: Hemispheric
      lateralization of visuospatial attention is a robust phenomenon and can be
      reliably determined using perfusion sensitive measurements. Future studies should
      focus on investigating lesion-related reorganization of attentional processing
      with blood-flow sensitive techniques.

PMID- 12048053
TI  - Prediction of movement following noxious stimulation during 1 minimum alveolar
      anesthetic concentration isoflurane/nitrous oxide anesthesia by means of middle
      latency auditory evoked responses.
AB  - This paper investigates the applicability of generalized dynamic neural networks
      for the design of a two-valued anesthetic depth indicator during
      isoflurane/nitrous oxide anesthesia. The indicator construction is based on the
      processing of middle latency auditory evoked responses (MLAER) in combination
      with the observation of the patient's movement reaction to skin incision. The
      framework of generalized dynamic neural networks does not require any data
      preprocessing, visual data inspection or subjective feature extraction. The study
      is based on a data set of 106 patients scheduled for elective surgery under
      isoflurane/nitrous oxide anesthesia. The processing of the measured MLAER is
      performed by a recurrent neural network that transforms the MLAER signals into
      signals having a very uncomplex structure. The evaluation of these signals is
      self-evident, and yields to a simple threshold classifier. Using only evoked
      potentials before the pain stimulus, the patient's reaction could be predicted
      with a probability of 81.5%. The MLAER is closely associated to the patient's
      reaction to skin incision following noxious stimulation during 1 minimum alveolar
      anesthetic concentration isoflurane/nitrous oxide anesthesia. In combination with
      other parameters, MLAER could contribute to an objective and trustworthy movement
      prediction to noxious stimulation.

PMID- 12048054
TI  - Motor disinhibition in affected and unaffected hemisphere in the early period of
      recovery after stroke.
AB  - OBJECTIVES: To investigate motor disinhibition in affected and unaffected motor
      areas in the acute stage after stroke and during the early period of recovery.
      METHODS: Fifteen patients with moderate to severe hemiparesis after acute
      unilateral stroke were compared with 10 healthy age-matched controls. We used
      paired transcranial magnetic stimulation to study intracortical inhibition and
      facilitation from the thenar eminence muscles on both sides. F-wave from the
      median nerve on both sides were recorded. The recordings were performed 5-7 days
      (T1) and 30 days after stroke. RESULTS: In 10 patients who showed the presence of
      reliable motor evoked potentials on the affected side, intracortical inhibition
      was significantly reduced. On the unaffected side intracortical inhibition (ICI)
      was significantly reduced in all patients. Patients who presented significant
      motor recovery after 30 days showed persistence of abnormal disinhibition in the
      affected hemisphere but a return to normal ICI in the unaffected hemisphere.
      Patients with poor motor recovery showed persistence of abnormal disinhibition on
      both sides. No significant changes were observed in F-wave amplitude.
      CONCLUSIONS: Motor disinhibition occurs on both sides after stroke in all acute
      stage patients. Changes in motor disinhibition on unaffected side also are
      related to motor recovery.

PMID- 12048055
TI  - Repetitive paired-pulse transcranial magnetic stimulation affects corticospinal
      excitability and finger tapping in Parkinson's disease.
AB  - OBJECTIVES: To study the effect of long trains of a recently established
      conditioning-test paired-pulse repetitive transcranial magnetic stimulation
      (rTMS) paradigm on corticospinal excitability and finger tapping speed. METHODS:
      We applied 900 inhibiting or facilitating paired-pulses or 900 real or sham
      single stimuli at 1Hz over the motor cortex contralateral to the dominant hand of
      9 healthy subjects and contralateral to the more affected hand of 11 patients
      with Parkinson's disease. RESULTS: In both groups, motor evoked potentials (MEPs)
      from suprathreshold pulses were larger after facilitating paired-pulses than
      after inhibiting paired-pulses. After real single-pulse rTMS and after either
      type of paired-pulse rTMS patients showed an increase in finger tapping frequency
      on the stimulated hand. Tapping was unchanged contralaterally, after sham
      stimuli, and in controls. Tremor and tapping frequencies were not correlated, nor
      was the change in MEP size correlated to the change in tapping frequency.
      CONCLUSIONS: Repetitive paired-pulses allow selective induction of corticospinal
      inhibition or facilitation, but do not enhance the transient improvement of
      finger motility induced by conventional single-pulse rTMS.

PMID- 12048056
TI  - Decrease of middle cerebral artery blood flow velocity after low-frequency
      repetitive transcranial magnetic stimulation of the dorsolateral prefrontal
      cortex.
AB  - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) has been tried
      therapeutically in a variety of neuropsychiatric disorders. Both, inhibition and
      activation of cortical areas may be achieved using different stimulation
      parameters. Using low-frequency rTMS (0.9 Hz), inhibition of cortical areas can
      be observed. METHODS: In the present study, 38 right-handed, healthy,
      normotensive subjects (aged 21-50 years, mean 30.2 years, SD=4.9; 17 women) were
      enrolled. Twenty-five participants received active rTMS (5 min of 0.9 Hz rTMS,
      stimulus intensity 90% of motor threshold) of the right dorsolateral prefrontal
      cortex. Sham stimulation (n=13 subjects) occurred in the same manner as active
      rTMS, except that the angle of the coil was at 45 degrees off the skull.
      Simultaneously, ipsilateral and contralateral maximal middle cerebral artery
      (MCA) flow velocity (and pulsatility index, PI) was monitored using transcranial
      Doppler sonography. RESULTS: In the group with active rTMS, maximal MCA flow
      velocity decreased from a baseline (before rTMS) of 101.6 cm/s (SD=26.0) to a
      mean of 92.6 cm/s (SD=23.7) immediately after rTMS, T=5.06, P<0.001. This equals
      a mean decrease of 9.0 cm/s (SD=8.3) or approximately 8.9% of baseline flow. Five
      and 10 min after rTMS, there was a return to baseline. PI significantly decreased
      10 min after rTMS (mean difference -0.05, SD=0.05, T=2.29, P<0.05). In the
      contralateral MCA, maximal flow velocity tended to increase 10 min after rTMS
      (mean difference +7.4 cm/s, SD=17.5; T=-2.03, P=0.054). With sham rTMS, no
      significant changes occurred. CONCLUSIONS: The results from our study support the
      hypothesis that low-frequency rTMS may influence cerebral blood flow (CBF) over
      short periods of time, inducing a temporary decrease of maximal CBF in the
      ipsilateral MCA followed by an increase in the contralateral MCA.

PMID- 12048057
TI  - High-resolution EEG mapping: a radial-basis function based approach to the scalp
      Laplacian estimate.
AB  - OBJECTIVES: The present study addressed a new scalp Laplacian mapping (LM)
      algorithm. METHODS: Using a radial-basis function (RBF) as the interpolation
      basis function, and the smallest arc length on the surface of a spherical head
      model as the distance measure between two measurement sites, a new RBF based
      approach to LM is formulated. RESULTS: With simulated data and empirical data,
      comparison between the new RBF based approach and the spherical spline function
      (SSF) based approach was conducted in a 4-concentric spheres head model, and the
      results show that the RBF based approach is better than the SSF based approach to
      LM. CONCLUSIONS: The new RBF based approach to LM provides an additional
      efficient way for the neural electrical activities imaging.

PMID- 12048061
TI  - Fulminant hepatic failure in a pediatric patient with active GB virus C (GBV
      C)/hepatitis G virus (HGV) infection.
AB  - We describe a rare case of a pediatric patient with active GB virus C (GBV
      C)/hepatitis G virus (HGV) infection who died of fulminant hepatic failure within
      less than a month after the onset of jaundice. The child tested negative for all
      other known hepatitis viruses and had no history of blood transfusions. This
      observation suggests that although GBV-C/HGV is usually not pathogenic to the
      liver, it may be associated with certain idiopathic forms of fulminant hepatitis.
      Whether this association is etiological or circumstantial remains to be seen.

PMID- 12048062
TI  - Measurement of HCV RdRp activity with C-terminal 21 aa truncated NS5b protein:
      optimization of assay conditions.
AB  - The non-structural protein 5b (NS5b) of hepatitis C virus (HCV), bearing an RNA
      dependent RNA polymerase (RdRp) activity, is considered as a new target of
      antiviral therapy. We expressed and purified the C-terminal 21 amino acid
      truncated NS5b protein fused with glutathione S-transferase (GST-5bC21) using
      Escherichia coli. With the highly purified GST-5bC21 protein, we established an
      in vitro assay system for RdRp activity by using poly(C) as the template and a 12
      mer oligo(rG) as the primer. The optimal conditions for testing various
      concentrations of template, primer and proteins were determined to 22 degrees C
      and a pH of 7.5. The addition of 2.5 mM Mn(2+) increased the activity profoundly,
      to a level fivefold higher than that in the presence of 10 mM Mg(2+). At higher
      concentrations of Mn(2+), GST-5bC21 is stable as compared with previously
      reported full-length NS5b expressed using insect cells or NS5b protein with the C
      terminal 18 amino acids deleted. This sensitive and easy to use quantitative
      assay system will provide a stable system for the screening of inhibitors for HCV
      RdRp.

PMID- 12048063
TI  - Randomized, controlled trial of natural interferon-alpha therapy for e-antigen
      positive chronic hepatitis B patients.
AB  - We evaluated the efficacy of long-term interferon (IFN) therapy in patients with
      e-antigen-positive chronic hepatitis B. The study design was a prospective,
      randomized controlled clinical trial. Fifty-three patients were randomly assigned
      into one of two groups, treated with 3 million units (MU) of IFN (low dose group;
      n=27) or 6 MU IFN (high dose group; n=26), administered twice weekly for 52
      weeks. Responders were defined as patients whose hepatitis B virus (HBV)-DNA
      level, determined by branched DNA signal amplification and hepatitis B e-antigen
      (enzyme immunoassay) were negative and whose serum alanine transaminase (ALT)
      levels fell to within the normal range (ALT<50 IU/l) at 6 month after termination
      of IFN therapy. One patient in high dose group was dropped out because of
      transfer. Remainder 52 patients were examined by intention-to-treat (ITT)
      analysis. The response rates by ITT analysis were 40.7% (11/27) in low dose group
      and 20% (5/25) in high dose group. The difference between low and high dose group
      was not statistically significant. Univariate analysis of clinical factors that
      contribute to the response demonstrated that IFN therapy had a significant effect
      when, (1) the serum HBV-DNA level was <200 Meq/ml prior to the commencement of
      IFN therapy (P=0.0327). (2) Transient acute exacerbation of ALT was present
      during or after IFN therapy (P=0.0311). Multivariate analysis showed that the
      risk ratio for the development of response in patients with serum HBV-DNA level
      of less than 200 Meq/ml was 3.60 compared with patients with that of 200 Meq/ml
      or more than 200 Meq/ml (95% CI, 1.012-12.81). In conclusion, the results of this
      trial show that: (1) long-term twice weekly IFN therapy could be a worthwhile
      strategy for e-antigen-positive chronic hepatitis B patients with serum HBV-DNA
      level of less than 200 Meq/ml and (2) patients with transient acute exacerbation
      of ALT during or after IFN therapy could often respond well after exacerbation of
      ALT.

PMID- 12048064
TI  - TT virus of certain genotypes may reduce the platelet count in patients who
      achieve a sustained virologic response to interferon treatment for chronic
      hepatitis C.
AB  - The platelet count increases after a sustained response to interferon (IFN)
      treatment for chronic hepatitis C (CH-C). However, the extent of the increase
      differs by patient. We investigated whether concurrent TT virus (TTV) infection
      interferes with the improvement of thrombocytopenia. Serial serum samples were
      obtained from 85 noncirrhotic CH-C patients who achieved a sustained virologic
      response for hepatitis C virus (HCV) upon IFN treatment, and tested for TTV DNA
      by three polymerase chain reaction (PCR) methods (UTR, N22 and TTV genotype-1).
      UTR PCR can detect essentially all TTV genotypes, whereas N22 PCR primarily
      detects four major TTV genotypes (1-4). Eighty-four patients (84/85, 99%) were
      positive for TTV DNA by UTR PCR, 27 (32%) by N22 PCR and 18 (21%) by TTV genotype
      1 PCR just before IFN treatment was started (baseline). A sustained virologic
      response for TTV was observed in 6% (5/84) by UTR PCR, 52% (14/27) by N22 PCR and
      56% (10/18) by TTV genotype-1 PCR. The platelet count was significantly lower in
      the N22 PCR-positive group than in the N22 PCR-negative group not only at
      baseline (14.9+/-3.8 vs. 18.1+/-6.4x10(4)/&mgr;l, P<0.05), but also at the non
      HCV-viremic state one year after the completion of IFN treatment (15.5+/-2.8 vs.
      18.6+/-5.5x10(4)/&mgr;l, P<0.05), the differences also being statistically
      significant by TTV genotype-1 PCR, but not by UTR PCR. These results suggest that
      certain TTV genotypes including genotype 1 may play a role in aggravating the
      thrombocytopenia of CH-C patients, either alone or in concert with HCV.

PMID- 12048065
TI  - Thrombopoietin receptor (c-Mpl) is constitutively expressed on platelets of
      patients with liver cirrhosis, and correlates with its disease progression.
AB  - Thrombocytopenia is one of the major complications of liver cirrhosis. Except for
      hypersplenism associated with portal hypertension, it is not known which
      abnormalities of thrombopoiesis cause thrombocytopenia. To evaluate
      thrombopoiesis in liver cirrhosis, we analyzed thrombopoietin (TPO) and its
      receptor c-Mpl levels in cirrhotic patients. Expression of c-Mpl on platelets and
      the serum level of TPO were investigated from 38 patients with various stages of
      liver cirrhosis by flow-cytometric analysis and enzyme-immuno assay. Samples
      obtained from 22 individuals without evidence of liver disease were used as
      controls. Neither platelet counts nor TPO levels correlated with disease
      progression defined by the Child-Pugh classification. c-Mpl was constitutively
      expressed on the platelets of cirrhotic patients, and its expression level was
      reduced with disease progression defined by the Child-Pugh classification. In
      this study, serum TPO did not fluctuate according to the grade of cirrhosis.
      However, its receptor c-Mpl, which is expressed on platelets, was decreased
      significantly in severely cirrhotic patients with thrombocytopenia. Thus, a
      correlation between reduced c-Mpl expression and the progression of liver
      cirrhosis was demonstrated. We conclude that, in addition to hypersplenism, the
      reduced expression of c-Mpl may play a significant role in the thrombocytopenia
      observed in severe liver cirrhosis.

PMID- 12048066
TI  - Portal-systemic encephalopathy in two patients without liver cirrhosis and portal
      hypertension.
AB  - The portal-systemic venous shunt is uncommon in patients without portal
      hypertension. We present two cases of portal-systemic encephalopathy due to
      extrahepatic shunt without liver cirrhosis and portal hypertension. Two women in
      their seventies were admitted to our hospital because of recurrent episodes of
      altered sensorium, drowsiness, slurred speech, disorientation, asterexis and high
      blood ammonia levels. There was no history of abdominal surgery or abdominal
      trauma. Clinical examination revealed no signs of portal hypertension or stigmata
      of chronic liver diseases. Brain CT and MRI scanning were unremarkable except for
      a high intensity signal in the basal ganglia on T1 weighted MRI images.
      Laboratory tests were almost normal except for the hyperammonemia occurring on
      several occasions. There was no evidence of liver cirrhosis by imaging. However,
      color Doppler showed an extra-hepatic shunt in both patients and pulsed Doppler
      showed decreased velocity and volume of the portal venous flow. These sonographic
      findings were confirmed during percutaneous transhepatic portography (PTP).
      Portal pressures measured during PTP were 9 and 11 mmHg. Needle biopsy ruled out
      idiopathic portal hypertension and liver cirrhosis. The diagnosis was portal
      systemic encephalopathy due to extra-hepatic portosystemic venous shunting. Both
      patients were treated by embolization of the shunting vessel with metallic coils.

PMID- 12048067
TI  - Acute ethanol administration down-regulates toll-like receptor-4 in the murine
      liver.
AB  - Acute ethanol administration temporarily decreases the sensitivity to endotoxin
      (lipopolysaccharide, LPS) in the liver. The purpose of this study was to
      investigate the changes of toll-like receptor (TLR)-4, a newly identified LPS
      receptor in macrophages, in the liver following acute ethanol administration.
      Male C57BL/6N mice were given a bolus intragastric administration of ethanol (5
      mg/g BW) through a gastric canula, and liver samples were obtained 2-48 h later.
      RAW264.7 macrophages were cultured in the presence of ethanol (100 mM) or LPS (10
      ng/ml) for up to 4 h. TLR-4 mRNA in the liver and RAW264.7 cells was detected by
      RNase protection assay. As expected, TLR-4 mRNA was clearly detected in the
      control liver; however, it was barely detectable in the liver 2-6 h after ethanol
      administration, followed by the gradual increase to the basal levels 48 h later.
      Interestingly, LPS (10 ng/ml), but not ethanol (100 mM), decreased TLR-4 mRNA in
      RAW264.7 macrophages in 4 h. Indeed, gut-sterilization by oral antibiotics
      pretreatment prevented the decrease in TLR-4 mRNA caused by acute ethanol
      administration, supporting the hypothesis that gut-derived endotoxin is involved
      in the mechanism. These findings clearly indicated that acute ethanol
      administration in vivo down-regulates TLR-4 expression in the liver. This
      phenomenon most likely explains the mechanism by which acute ethanol blunts the
      response of Kupffer cells to LPS transiently.

PMID- 12048068
TI  - Enhanced GLUT2 gene expression in an oleic acid-induced in vitro fatty liver
      model.
AB  - Previous reports have shown that the liver-type glucose transporter GLUT2 gene
      expression is upregulated in the liver of obese and diabetic animals and in human
      subjects. This phenomenon is correlated with an increased glucose output from the
      liver; however, the regulatory mechanism is not clear. To investigate the
      relationship between hepatic steatosis, frequently found in obese and diabetic
      patients, and GLUT2 gene expression, we developed an oleic acid-induced in vitro
      fatty liver model. Lipid-accumulated cells morphologically mimicking hepatic
      steatosis were successfully induced in the human HepG2 cell line by 24-h culture
      with oleic acid at 1 mM. The cells with steatosis showed increased levels of
      intracellular triglycerides and apolipoprotein B, which were reduced in the
      presence of bezafibrate at 100 &mgr;g/ml. GLUT2 mRNA expression estimated by semi
      quantitative reverse transcription polymerase chain reaction was increased in the
      cells with steatosis. Bezafibrate inhibited GLUT2 mRNA expression in the cells
      with and without steatosis. These results suggest that hepatic steatosis causes
      the enhancement of hepatic GLUT2 mRNA expression, which may be associated with
      gluconeogenesis and insulin resistance.

PMID- 12048069
TI  - Intrahepatic huge hematoma due to rupture of small hepatocellular adenoma: a case
      report.
AB  - Hepatocellular adenoma sometimes causes intraperitoneal hemorrhage. It is,
      however, rare for small hepatocellular adenoma to cause intrahepatic huge
      hemorrhage without intraperitoneal bleeding. Here we describe such a rare case of
      hepatocellular adenoma with huge intrahepatic hemorrhage in a 25-year-old female,
      who had taken oral contraceptives for the last 2 weeks. She was admitted to our
      hospital with a sudden onset of right-upper-quadrant abdominal pain and
      temporally fell in shock state. Plain CT depicted low density area measuring more
      than 13 cm in diameter in the right lobe of the liver. Huge tumor was also
      suggested by abdominal ultrasound, contrast enhanced CT, magnetic resonance
      imaging (MRI) and angiography. The patient was diagnosed as intrahepatic rupture
      of hepatic tumor. Because of the risk of re-hemorrhage and malignancy, she
      underwent right hepatic lobectomy. Histopathologial examination of the resected
      specimen showed a typical small hepatocellular adenoma with the surrounding huge
      hematoma in the liver. The case presented here is very rare but seems to be
      suggestive to the natural course and management of hepatocellular adenoma.

PMID- 12048070
TI  - Acute traumatic aortic rupture: early stent-graft repair.
AB  - OBJECTIVE: Prospective evaluation of early stent-graft repair of acute traumatic
      aortic rupture. METHODS: Twelve patients with acute traumatic aortic rupture of
      the descending aorta, out of a series of 337 endovascular aortic procedures, were
      treated by implantation of self-expanding stent-grafts. The procedures were
      performed within a mean post-injury time-period of 5+/-7 days (median: 1 day).
      The feasibility of stent-grafting was assessed by CT scanning and echography.
      Implantation was performed under local (n=6), or general anesthesia (n=6) if
      patients were already intubated (n=5) or required a common iliac artery access
      (n=1). RESULTS: The immediate technical success rate was 100%. There were no post
      procedure complications in all but one patient, who died 12 h postoperatively (8%
      mortality). Complete sealing of the aortic rupture in the remaining 11 patients
      was confirmed by postoperative CT scans. There were no intervention-related
      morbidity or mortality during the mean follow-up of 17 months. One patient with
      peri-graft leakage was successfully repaired with an additional stent-graft 12
      months postoperatively. CONCLUSION: Non-delayed or early stent-grafting in acute
      traumatic rupture of the descending aorta is feasible. This technique seems to be
      a valuable option, in particular when associated lesions may interfere with the
      surgical outcome. Immediate post-procedural CT scanning and/or echography should
      be performed, in order to rule out residual leakage.

PMID- 12048071
TI  - Endoluminal stent-graft placement in patients with acute aortic dissection type
      B.
AB  - OBJECTIVES: This study was performed to evaluate the feasibility, safety and
      effectiveness of endovascular stent-grafting in treating Stanford type B acute
      aortic dissection. We describe our first clinical experiences and initial results
      with stent-grafting across the primary entry tear in patients with acute aortic
      dissection type B. METHODS: Between March 2000 and August 2001, nine patients
      with acute type B dissection were treated endoluminally by stent-graft
      implantation. There were seven male and two female patients with a mean age of 63
      years (between 48 and 85 years). In all nine patients aortic dissection was
      diagnosed by multislice computed tomography (CT) angiography. All nine patients
      had a maximal aortic diameter of 5.5 cm or more and recurrent pain, one patient
      showed hemoptysis. This patient with signs of a contained rupture was treated
      under emergency condition, the eight remaining patients were in hemodynamic
      stabile condition at the time of intervention. The GORE Excluder stent-graft
      system was used in eight patients (mean 1.8 stents/patient) and the TALENT stent
      graft system in one patient, which were introduced transfemorally. RESULTS: The
      primary entry tear could be sealed successfully in all nine patients. Complete
      thrombosis of the false thoracic aortic lumen was obtained in two patients, in
      the remaining seven patients the false lumen was obliterated in the area of the
      thoracic aorta but perfused via re-entries in the abdominal region. No severe
      intraoperative complications occurred. One patient developed bilateral incomplete
      paraplegia with motor and sensory deficits affecting completely the right leg and
      partially the left leg, 14 h after intervention. A cerebrospinal fluid drainage
      was initiated by inserting a lumbar catheter. All nine patients, including the
      patient with the transient paraplegia, could be discharged from the hospital in
      excellent condition and without remaining neurologic deficits. Control CT scans
      showed a reduction of the false lumen from 2.34+/-0.58 to 0.7+/-0.44 cm and an
      increase of the true lumen from 1.56+/-0.5 to 4.10+/-0.6 cm in the thoracic
      aortic region. Mean ICU stay was 1.8 days, mean postoperative hospital stay was
      7.6 days. CONCLUSIONS: Stent-grafting of acute type B dissections may represent a
      very effective and promising new method by closure of the primary entry tear,
      thereby minimizing the risk of rupture of the thoracic aorta and optimizing
      distal perfusion by decompression of the true lumen.

PMID- 12048072
TI  - Thoracoabdominal or descending aortic aneurysm repair after preoperative
      demonstration of the Adamkiewicz artery by magnetic resonance angiography.
AB  - OBJECTIVE: The outcome of thoracoabdominal or descending aortic aneurysm repair
      after preoperative demonstration of the artery of Adamkiewicz (ARM) by magnetic
      resonance angiography (MRA) was investigated. METHODS: Between January 2000 and
      December 2001, 40 consecutive patients who had aneurysms of the thoracoabdominal
      or descending aorta underwent preoperative MRA to visualize the ARM. Thirty-two
      patients underwent replacement of the aneurysms, and 25 patients (TAAA, 11; TAA,
      14) underwent replacement of the aneurysms with preoperative detection of the
      ARM. Only intercostal or lumbar arteries in aneurysms, which were detected as the
      origin of the ARM, were reattached to the graft. The results of thoracoabdominal
      aortic aneurysm operations in 11 patients in whom the ARM was preoperatively
      detected (group I) were compared with the results of TAAA operations in 26
      patients in whom the ARM was not preoperatively detected (group II). RESULTS: MRA
      demonstrated the ARM in 29 (73%) of the 40 patients. The laterality of the
      arteries originated from the left side in 29 (100%) and between Th9 and Th12 in
      25 (86%), between Th9 and L1 in 28 (97%) of the 29 patients. No spinal cord
      injury occurred in patients (TAAA and TAA) in whom the ARM had been
      preoperatively detected. Major complications following TAAA operations included
      paraplegia (0% in group I and 8% in group II), respiratory failure (9% in group I
      and 23% in group II), and renal failure requiring hemodialysis (18% in group I
      and 22% in group II). Operation times were 439+/-99 min in group I and 620+/-200
      min in group II (P=0.008). CONCLUSIONS: Preoperative detection of the ARM is
      possible by MRA and is very useful for reducing the incidence of ischemic injury
      of the spinal cord and for reducing the time of an operation for repair of an
      aneurysm of the thoracoabdominal or descending aorta.

PMID- 12048073
TI  - Hemodynamic analysis of descending versus ascending aortomyoplasty, and
      comparison with intra-aortic balloon pump.
AB  - OBJECTIVE: Descending and ascending aortomyoplasty are two surgical procedures
      intended to induce hemodynamic benefits similar to those of the intra-aortic
      balloon-pump (IABP). To date, there have been no studies comparing the two
      surgical techniques. The objective of this study was to compare coronary blood
      flow augmentation and afterload reduction as produced by descending and ascending
      aortomyoplasty counterpulsation METHODS: Twenty-two mongrel dogs (18-35 kg)
      underwent IABP application (n=7), descending (n=8), or ascending (n=7)
      aortomyoplasty. Left anterior descending (LAD) coronary artery blood flow was
      measured using a Transonic Doppler flow probe. Left ventricular pressure as well
      as aortic pressures proximal and distal to either the aortomyoplasty site or the
      IABP position were monitored continuously. RESULTS: Descending aortomyoplasty
      induced higher elevation in the LAD blood flow during assisted beats (27% from
      10.8+/-4 to 13.8+/-6 ml/min, P<0.001) than that induced by either ascending
      aortomyoplasty (19% from 11.7+/-5 to 14+/-5 ml/min, P<0.001) or IABP
      counterpulsation (18% from 8.6+/-3 to 10.2+/-4 ml/min, P<0.001). Conversely,
      while ascending aortomyoplasty reduced the left ventricular end-diastolic
      pressure by 16% (from 60+/-18 to 50+/-22 mmHg, P<0.001), similar to the 16% after
      load reduction achieved by the IABP counterpulsation, descending aortomyoplasty
      failed to induce afterload reduction. CONCLUSIONS: Descending aortomyoplasty
      produces higher coronary blood flow augmentation than either ascending
      aortomyoplasty or IABP. However, afterload reduction comparable to that achieved
      by IABP was observed only with ascending aortomyoplasty and not with descending
      aortomyoplasty.

PMID- 12048074
TI  - Acceptance of gene therapy by the heart surgery patient.
AB  - OBJECTIVE: The aim of the present study was to evaluate the attitude of cardiac
      surgery patients towards gene therapeutic approaches to heart disease. METHODS:
      One hundred and fifty patients having undergone coronary artery bypass grafting
      (n=97), valvular operations (n=40) or combined procedures (n=13) were personally
      interviewed prior to discharge using a self designed questionnaire. RESULTS:
      Seventeen percent of the surveyed patients were unable to complete the interview
      because of total non-understanding of the topic. Of the remaining patients, 33%
      could basically define the term 'gene'. After explanation of gene therapy
      principles 70% believed that gene therapy protocols had already been started
      clinically. Fifty-two percent would accept enrollment in a clinical trial (85% in
      cases of otherwise incurable disease). If clinical gene transfer would be carried
      out 73% of patients would accept adenovirus as a vector, 94 and 80%,
      respectively, would accept catheter-based intervention or surgery for performance
      of gene therapy. Fifty-four percent would agree to a prophylactic gene therapy
      protocol. CONCLUSIONS: We conclude that the general attitude of heart surgery
      patients regarding gene therapy is positive. A considerable number of patients
      are unable to understand the basic principles of gene therapy. These data can be
      useful for planning of clinical gene therapy trials and show potential
      difficulties in obtaining informed consent.

PMID- 12048075
TI  - Cardioprotection by breathing hyperoxic gas-relation to oxygen concentration and
      exposure time in rats and mice.
AB  - OBJECTIVES: Breathing a hyperoxic gas (> or =95% O(2)) protects against ischaemia
      reperfusion injury in rat and mouse hearts. The present study investigated how
      oxygen concentration and duration of hyperoxic exposure influenced
      cardioprotection, and whether hyperoxia might induce delayed cardioprotection
      (after 24 h). METHODS: Animals were kept in normal air or in a hyperoxic
      environment, and their hearts were isolated and Langendorff-perfused immediately
      or 24 h thereafter. Global ischaemia was induced for 25 min in rats and 40 min in
      mice, followed by 60 min of reperfusion. Infarct size was determined by triphenyl
      tetrazolium chloride staining. RESULTS: In rats exposure to > or =95, 80, and
      60%, but not to 40% of oxygen immediately before heart isolation and perfusion
      improved postischaemic functional recovery. Eighty or more percent of oxygen also
      reduced infarct size. A preconditioning-like effect could be evoked by 60 or 180
      min of hyperoxia, giving both immediate and delayed protection. In the mouse
      heart protection could be induced by pretreatment for 15 or 30, but not by 60 min
      with > or =95% oxygen. The protective effect of hyperoxia in mice could be evoked
      in the immediate model only. CONCLUSIONS: Hyperoxia protects the isolated rat and
      mouse heart against ischaemia-reperfusion injury, but some species-different
      responses exist. The protection depends on both oxygen concentration in inspired
      air, and duration of hyperoxic exposure.

PMID- 12048076
TI  - Continuous monitoring of myocardial acid-base status during intermittent warm
      blood cardioplegia.
AB  - OBJECTIVE: Intermittent warm blood cardioplegia (IWBC) is a well-established
      technique for myocardial protection during cardiac operations. According to
      standardized protocols, IWBC administration is currently performed every 15-20
      min regardless of any individual variable and in the absence of any instrumental
      monitoring. We devised a new system for continuous measurement of the acid-base
      status of coronary sinus blood for on-line evaluation of myocardial oxygenation
      during IWBC. METHODS: In 19 patients undergoing cardiac surgery for coronary
      artery bypass graft and/or valve surgery and receiving IWBC (34-37 degrees C) by
      antegrade induction (3 min) and retrograde or antegrade maintenance (2 min) every
      15 min, continuous monitoring of myocardial oxygenation and acid/base status was
      performed by means of a multiparameter PO(2), PCO(2), pH, and temperature sensor
      (Paratrend7 (R), Philips Medical System) inserted into the coronary sinus.
      RESULTS: Mean cross-clamping time was 76+/-26 min; ischemic time was 13+/-0.2
      min. pH decline was not linear, showing an initial fast decline, a point of
      flexus, and a progressive slow decline. After every ischemic period, the pH
      adaptation curve showed a complex pattern reaching step-by-step lower minimum
      levels (7.28+/-0.14 during the first ischemic period, to 7.16+/-0.19 during the
      third ischemic period - P=0.003). PO(2) decreased rapidly at 90% in 5.0+/-1.2 min
      after every reperfusion. During ischemia, PCO(2) increased steadily at 1.6+/-0.1
      mmHg per minute, with progressively incomplete removal after successive
      reperfusion, and progressive increase of maximal level (42+/-12 mmHg during the
      first ischemic period, to 53+/-23 mmHg during the third ischemic period -
      P=0.05). CONCLUSIONS: Myocardial oxygen, carbon dioxide, and pH show marked
      changes after repeated IWBC. Myocardial ischemia is not completely reversed by
      standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH
      after each reperfusion. Progressive increase of reperfusion durations or direct
      monitoring of myocardial oxygenation could be advisable in cases of prolonged
      cross-clamping time.

PMID- 12048077
TI  - Insulin and local growth factor PDGF induce intimal hyperplasia in bypass graft
      culture models of saphenous vein and internal mammary artery.
AB  - OBJECTIVE: In arteriosclerosis and bypass graft stenosis, intimal proliferation
      is controlled by local and systemic growth factors, such as platelet derived
      growth factor (PDGF) or insulin. Intimal hyperplasia can be produced in organ
      culture models. Our aim was to compare neointima formation in two organ culture
      models of internal mammary artery (IMA) and saphenous vein (SV), with special
      reference to the influence of systemic and local growth stimuli. METHODS: Rings
      of freshly isolated human SV and IMA were cultured over a 3-, 6- or 8-day period.
      They were distributed into five groups of incubation protocols: incubation with
      10% serum; insulin 50 ng/ml and 100 ng/ml; PDGF-BB 5 ng/ml and 10 ng/ml. Frozen
      sections of cultured rings and pre-culture segments were subjected to elastic
      stain and immunohistochemistry. Antibodies directed against beta-actin and smooth
      muscle alpha-actin were used to characterize smooth muscle cell phenotype and
      against proliferating cell nuclear antigen (PCNA) to demonstrate proliferating
      cells. RESULTS: Growth factor incubation caused massive intimal hyperplasia with
      increased elastic fibers in SV and intimal smooth muscle cell as well as matrix
      accumulation in IMA. Intimal thickening, PCNA and beta-actin expression reached
      their maximum on day 6 of culture. In both culture models, serum, insulin and
      PDGF caused increasing intimal thickening, with more pronounced effects in SV.
      CONCLUSIONS: These organ culture models demonstrate the effects of insulin and
      PDGF on intimal hyperplasia in IMA and SV representing models for
      arteriosclerosis and bypass graft stenosis and stressing the role of insulin and
      growth factors for neointima development.

PMID- 12048078
TI  - Randomized comparative study of radial artery and right gastroepiploic artery in
      composite arterial graft for CABG.
AB  - OBJECTIVES: Arterial grafts have been used to achieve better long-term results
      and improve graft patency in coronary artery bypass grafting. Composite graft was
      proposed to overcome inconveniences of proximal anastomoses to the aorta and
      increase the use and surgical options of arterial grafts. However, lack of
      prospective randomized studies with this kind of grafts is evident. We compare
      the results of composite Y-grafts of the radial artery (RA) and the right
      gastroepiploic artery (RGEA) proximally anastomosed to the left internal thoracic
      artery (LITA) for CABG, evaluated through angiography, in a prospective
      randomized study. METHODS: Between August 1998 and November 1999, 60 patients
      were randomly divided into two groups: group I (GI) received RGEA graft and group
      II (GII), RA graft. LITA was used to graft the left anterior descending artery
      and RGEA or RA was placed to obtuse marginal or first diagonal branch. The right
      coronary artery branches was grafted with saphenous vein graft (SVG) when
      necessary. All coronary arteries receiving arterial grafts had > or =75% proximal
      stenosis and diameter > or =1.5 mm. RESULTS: GI and GII preoperative data were
      similar, 63 distal anastomoses were performed with the LITA, 32 with the RA and
      32 with the RGEA. There were two perioperative deaths (3.3%), one in each group,
      none related to cardiac causes. Four (6.6%) q-wave myocardial infarctions were
      found and two (3.3%) patients showed low cardiac output syndrome. Angiography was
      performed in all surviving patients from the 8th to 15th postoperative day and
      showed a patency rate of 96.5% (56/58) for LITA, 89.6% (26/29) for RA and 68.9%
      (20/29) for RGEA, with a statistically significant difference between RGEA and RA
      (P=0.025). CONCLUSIONS: Radial artery had better early results than right
      gastroepiploic artery. Use of the LITA as inflow graft seems not to affect its
      good patency. Use of the RGEA as composite graft should not be encouraged. Long
      term follow-up with objective investigation and randomized trials is required to
      confirm better results of composite conduits.

PMID- 12048079
TI  - Bilateral pedicled internal thoracic artery grafting.
AB  - BACKGROUND: Pedicled bilateral internal thoracic artery grafting (BITA) has been
      discouraged in historical high-risk groups such as diabetes mellitus (DM), renal
      failure, old age, and obesity because of reported high incidence of
      mediastinitis. However, considering the fact that there are abundant short and
      long-term results including angiography study about the conventional pedicled
      grafts, it might be worthwhile reassessing the results of pedicled BITA grafting
      with modern techniques by a disciplined surgical team before abandoning the
      method. METHODS: Between September 1989 and September 1999, 1371 patients
      underwent isolated coronary artery bypass grafting (CABG) in Kumamoto central
      hospital. Of these patients, 558 patients who had bilateral ITA strategy (mean
      age 63.0+/-9.2 years, 13-79) were studied. The method of harvest of ITAs is
      consistently the use of conventional pedicled grafts. The use of bone wax and
      unnecessary electrocautery injury to the periostium or cartilage were avoided as
      much as possible. The only change in the surgical technique in the study period
      is the application of the pinpoint hemostasis for the presternal tissues from
      August 1997 (late period). RESULTS: In late period, there were significantly more
      patients with sternal sepsis risk factors such as diabetes mellitus (early: late;
      19.3% vs. 34.8%, P<0.00003), and renal failure (0.3 vs. 9.7%, P<0.0001) as well
      as patients who had gastroepiploic artery grafting (16.9 vs 48.5%, P<0.0001) and
      those who required aortic non-touch technique (2.1 vs. 7.9%, P<0.001). The
      percentage of the patients receiving BITA grafting among the isolated CABG
      patients increased in the late period from 31.7% (331/1043) to 69.2% (227/328)
      (P<0.001), reflecting that a more aggressive approach towards bilateral ITA and
      arterial grafting has been taken in the late period. Overall operative mortality
      was 1.1% (n=6). Mediastinitis occurred in seven patients (1.3%). Of these, only
      one mediastinitis occurred in late period (0.4%). No mediastinitis occurred in 23
      chronic renal dialysis patients. Among the 143 DM patients, there were three
      mediastinitis (2.1%). Of three, only one occurred in late period, yielding 1.3%
      mediastinitis rate. There was one mediastinitis (0.7%) among 134 elderly patients
      more than 70 years of age. Univariate analysis identified obesity as a risk
      factor for mediastinitis. And there was a trend of decreasing mediastinits in
      late period but did not reached a statistical significance (P<0.2). Multivariate
      analysis identified obesity and arteriosclerosis obliterates as independent risk
      factors. Neither diabetes mellitus, dialysis, female gender, nor old age were
      significant independent predictors of mediastinitis. Despite the significantly
      high percentage of high-risk patients in late group, there were no significant
      difference in mortality and morbidity between the two groups. CONCLUSION:
      Pedicled BITA grafting is feasible with acceptable morbidity and shouldn't be
      abandoned even in high-risk patients such as DM, old age, and dialysis,
      especially combined with pinpoint-hemostasis, avoiding excessive use of bone wax,
      and strict aseptic technique. These point require a surgical team familiar with
      these techniques to maintain adequate skills in conduit procurement.

PMID- 12048080
TI  - Mid-term results after extensive vein patch reconstruction and internal mammary
      grafting of the diffusely diseased left anterior descending coronary artery.
AB  - OBJECTIVE: To analyze the results of extensive reconstruction of the left
      anterior descending coronary artery (LAD) by an autologous vein patch, with or
      without endarterectomy (EA), associated with left internal mammary artery
      grafting onto the patch. METHODS: Between January 1994 and April 2001, among 5871
      myocardial revascularizations, 83 patients (1.4%), 77 male (93%), with a mean
      age+/-SD of 64+/-8 years (range 44-84) underwent the above mentioned procedure.
      Seventy-three of them (88%) were in Canadian Cardiovascular Society (CCS) Class
      III or IV, and 78 (94%) had a three-vessel disease. Mean preoperative ejection
      fraction was 58+/-12%. Risk factors included hypertension (63%), family history
      (51%), hyperlipidemia (41%), smoking (38%), diabetes (19%). Mean number of
      anastomoses/patient was 3+/-0.6. Mean length of vein patch was 2.8+/-0.9 cm
      (range 2-6 cm). A total of 16% of the patients underwent associated LAD-EA (mean
      cardiopulmonary bypass time: 132+/-21 min; mean aortic crossclamp time: 81+/-15
      min). RESULTS: There was one hospital death (recurrent MI, 1.2%). Seven patients
      (8%) had a perioperative myocardial infarction, in three cases in the region
      supplied by the LAD (none after associated LAD-EA). Mean follow-up period was
      47+/-20 months (range 5-90) and is 99% complete. There were five late cardiac
      deaths (6%). A total of 74% survivors have no symptoms, 12% are in CCS Class I
      II, and 14% in III-IV. Actuarial freedom from recurrent angina at 3 and 5 years
      is 77 and 69%, respectively. Follow-up angiograms (49 patients, 60%) revealed a
      full patent LAD graft in 82% of the cases (GI), versus poor run-off/occluded
      graft in the remaining 18% (GII). Anginal status was significantly worse in GII
      patients (P<0.05). CONCLUSIONS: Extended reconstruction of the LAD coronary
      artery increases surgical risk. The procedure however enhances the probability
      for a complete revascularization in patients with an unfavourable anatomical
      substrate, with acceptable mid-term results.

PMID- 12048081
TI  - Early extubation does not increase complication rates after coronary artery
      bypass graft surgery with cardiopulmonary bypass.
AB  - BACKGROUND: With the evolution of anesthesia and surgical procedures, fast track
      extubation has gained an increased interest, mainly based on the possibility of
      reducing health costs seemingly without compromising patient care. AIM: To
      compare two groups of patients submitted to a non-fast track extubation and a
      fast track extubation protocol after coronary artery bypass graft surgery with
      cardiopulmonary bypass, regarding their times of ventilation and intubation and
      their complication rates in the postoperative period. METHODS: During the year of
      1998, 323 sequential patients scheduled for isolated coronary artery bypass graft
      surgery with cardiopulmonary bypass were enrolled in the study. Fifty-nine
      patients were excluded due to preoperative use of emergent mechanical and/or
      inotropic hemodynamic support, low body mass index (< or =18-20 kg/m(2)),
      reoperations for acute surgical complications, off-pump coronary artery bypass
      graft surgery, severe respiratory disease, recent myocardial infarction (< or =7
      days) and absence of relevant data. Previous myocardial infarction (> or =7
      days), prophylactic intraaortic balloon pump and use of postoperative vasoactive
      drugs were not exclusion criteria. We compared 76 patients sequentially submitted
      to anesthesia by one of the authors with a fast track extubation protocol and 188
      patients sequentially submitted to anesthesia by others in the same period and
      using a conventional anesthetic protocol. RESULTS: Demographic data, previous
      medical and cardiac history, preoperative medication and operative data were all
      similar between the two groups. The mean ventilation and intubation times were
      significantly shorter in the fast track extubation group than in the non-fast
      track extubation patients (30 min vs. 7 h and 50 min vs. 8 h, respectively).
      Forty-two percent of patients in the fast track extubation group were extubated
      on arrival at the intensive care unit. Morbidity and mortality were similar in
      both groups. CONCLUSIONS: The study shows that a very fast track extubation
      protocol may be safely implemented in patients submitted to coronary artery
      bypass graft surgery with cardiopulmonary bypass.

PMID- 12048082
TI  - Preoperative prediction of early mortality in redocoronary artery surgery.
AB  - OBJECTIVES: Construct a predictive model for early mortality in coronary
      reoperations (RECABG). METHODS: Five hundred and forty one RECABG (1987-1998)
      were studied by univariate and multivariate analysis. Stepwise selective
      procedure (p<0.05) was used to identify a subset of variables with prognostic
      value for early mortality. This subset was used to calculate a prognostic score
      'S' and a predicted probability 'P' for early mortality, P=1/1+e(-S). Sensitivity
      analysis was used for evaluation. RESULTS: The best predictive variables for
      early mortality were diabetes, vascular-, lung-disease, a myocardial infarction
      between the primary and the RECABG, acute- and emergency operation and the
      operative period. The prognostic accuracy (receiver operating characteristics
      curve (ROC) area) was 80%. Observed probabilities compare well with the predicted
      probabilities, and patients were classified in low risk (5%), intermediate risk
      (15%), high risk (30%) and very high risk (40%). A predicted probability of > or
      =0.40 was used as cut-off point for the prognostic test. The specificity of this
      test was 97%, sensitivity 33%, predictive value of a positive test 63% and 90%
      for a negative test. CONCLUSIONS: The results show that individual patients
      presented for RECABG, can be stratified according to their early mortality risk.
      This information can be used to inform the patient, and also to discus the
      opportunity of the RECABG.

PMID- 12048083
TI  - Thyroid hormone metabolism in pediatric cardiac patients treated by continuous
      povidone-iodine irrigation for deep sternal wound infection.
AB  - OBJECTIVE: The purpose of this study was to assess the influence of povidone
      iodine mediastinal irrigation used for the treatment of deep sternal wound
      infection (DSWI) on thyroid function. METHODS: Thyroid function was studied in 18
      pediatric cardiac patients treated with continuous povidone-iodine irrigation for
      DSWI. The median age of patients was 8 months (18 days-5.3 years). Serum
      concentrations of total triiodothyronine (TT3), total thyroxine (TT4), free
      triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH),
      reverse triiodothyronine (rT3) and thyroxine-binding globulin (TBG) were measured
      at three time points: (a) prior to mediastinal reexploration (before povidone
      iodine exposure); (b) immediately after discontinuation of povidone-iodine
      irrigation; (c) 2 weeks after discontinuation of mediastinal irrigation. Urinary
      iodine excretion was examined on the last day of povidone-iodine exposure.
      RESULTS: Prior to the mediastinal reexploration, the median TT3 and TT4 levels
      were below the normal range, then increased significantly to concentrations
      within the normal range. The median serum FT3 levels were within the normal range
      throughout the observation period, though a significant increase of FT3 levels
      was observed after discontinuation of irrigation. The median serum FT4
      concentrations were within the normal range prior to irrigation and did not
      change significantly. The median rT3 levels were within the normal range, close
      to upper normal limit. The median TBG levels were within the normal range
      throughout the observation period, though a significant increase of TBG levels
      was observed during the period of mediastinal irrigation. The median TSH level
      was within the normal range prior to mediastinal irrigation and did not change
      significantly. Urinary iodine concentrations in infants with povidone-iodine
      irrigation were significantly higher 6700 microg/l (range, 1600-15000 microg/l)
      than in the group of 53 healthy infants 200 microg/l (range, 20-780 microg/l,
      P<0,001). CONCLUSIONS: Our data showed that the use of povidone-iodine irrigation
      in the patients with DSWI has not lead to any significant alteration in thyroid
      function within the study period.

PMID- 12048084
TI  - Biventricular repair of double outlet right ventricle with non-committed
      ventricular septal defect (VSD) by VSD rerouting to the pulmonary artery and
      arterial switch.
AB  - OBJECTIVES: Biventricular repair of double outlet right ventricle non-committed
      ventricular septal defect (DORVncVSD) is usually achieved by a VSD rerouting to
      the aorta. This technique can be limited by the presence of tricuspid chordae and
      by the pulmonary artery to tricuspid valve distance. Furthermore, there is an
      important risk of late subaortic obstruction related to the long patch required
      that creates a potential akinetic septal area. Presented here is another
      technique; by VSD rerouting to the pulmonary infundibulum and arterial switch.
      METHODS: Ten patients, with DORVncVSD, underwent a VSD rerouting to the pulmonary
      infundibulum followed by arterial switch. Seven had a previous pulmonary artery
      banding and one a moderate infundibular stenosis. The median age at surgery was
      16 months (range 3 weeks to 4.5 years). All patients had a bilateral
      infundibulum, with a large persistent subaortic conus, D malposition of the
      aorta, side-by-side vessels and double loop coronary patterns. The VSD was
      perimembranous with inlet or trabecular extension. Subaortic obstruction was
      constant. The VSD was severely distant from both the aortic and the pulmonary
      annulus. The operation was conducted through a combined approach. The VSD was
      constantly enlarged superiorly. The almost permanent subaortic obstruction was
      released. The VSD was always found quite close to the pulmonary infundibular
      ostium. The arterial switch technique was adapted to the complex coronary
      anatomy. RESULTS: There was one non-cardiac death. At a mean follow-up of 20
      months, all nine survivors are in NYHA class I, in sinus rhythm, and have no
      subaortic gradient greater than 15 mm. CONCLUSION: This technique of VSD
      rerouting to the pulmonary artery and arterial switch limits greatly the size of
      the rerouting patch, respects the tricuspid chordae and is independent of the
      pulmonary artery-tricuspid valve distance. In this early series of biventricular
      repair of DORVncVSD, the VSDs were always found close to the pulmonary artery,
      allowing this new type of repair.

PMID- 12048085
TI  - Anatomical mismatch of the pulmonary autograft in the aortic root may be the
      cause of early aortic insufficiency after the Ross procedure.
AB  - OBJECTIVE: Early aortic insufficiency can be a problem after the Ross procedure.
      Anatomical mismatch and an inexact surgical technique may lead to distortion of
      the normal pulmonary valve geometry and subsequent incorrect leaflet coaptation
      and valve insufficiency. In this study, we assessed the efficacy of changing and
      improving the surgical technique to minimize the early pulmonary autograft valve
      failure. The modifications and the strategy are discussed. METHODS: From January
      1995 to February 1999, a total of 77 adults underwent the Ross procedure for
      aortic valve replacement at Sahlgrenska University Hospital. The operative
      technique used was full free-standing aortic root replacement with a pulmonary
      autograft in all cases. In the first 24 cases, the diameter of the pulmonary
      roots was seldom measured, eye-balling was used to exclude anatomical mismatch
      due to a dilated aortic root, and only one attempt of correction was made, which
      failed. In the other 53 cases, the technique was improved by: (1) reducing the
      aortic anulus diameter in cases with moderate dilatation; (2) excluding cases
      with severe dilatation of the aortic annulus; (3) adjusting the diameter of the
      sinotubular junction of the aorta to the diameter of the sinotubular junction of
      the pulmonary artery; (4). reimplanting the left ostium in the autograft, and (5)
      changing the proximal anastomosis technique. RESULTS: In this study, we had an
      early aortic incompetence of grade 2 in eight patients among the first 24
      patients. In the other 53 patients, postoperative echocardiography at 1 week
      revealed aortic insufficiency of grade 2 in two patients. CONCLUSIONS: Aortic
      insufficiency after the Ross procedure can be minimized by patient selection,
      intraoperative correction of anatomical mismatch and improved surgical technique.

PMID- 12048086
TI  - A new source for cardiovascular tissue engineering: human bone marrow stromal
      cells.
AB  - OBJECTIVE: Vascular-derived cells represent an established cell source for tissue
      engineering of cardiovascular constructs. Previously, cell isolation was
      performed by harvesting of vascular structures prior to scaffold seeding. Marrow
      stromal cells (MSC) demonstrate the ability to differentiate into multiple
      mesenchymal cell lineages and would offer an alternative cell source for tissue
      engineering involving a less invasive harvesting technique. We studied the
      feasibility of using MSC as an alternative cell source for cardiovascular tissue
      engineering. METHODS: Human MSC were isolated from bone marrow and expanded in
      culture. Subsequently MSC were seeded on bioabsorbable polymers and grown in
      vitro. Cultivated cells and seeded polymers were studied for cell
      characterization and tissue formation including extracellular matrix production.
      Applied methods comprised flow cytometry, histology, immunohistochemistry,
      transmission (TEM) and scanning electron microscopy (SEM), and biochemical
      assays. RESULTS: Isolated MSC demonstrated fibroblast-like morphology. Phenotype
      analysis revealed positive signals for alpha-smooth muscle actin and vimentin.
      Histology and SEM of seeded polymers showed layered tissue formation. TEM
      demonstrated formation of extracellular matrix with deposition of collagen
      fibrils. Matrix protein analysis showed production of collagen I and III. In
      comparison to vascular-derived cell constructs quantitative analysis demonstrated
      comparable amounts of extracellular matrix proteins in the tissue engineered
      constructs. CONCLUSIONS: Isolated MSC demonstrated myofibroblast-like
      characteristics. Tissue formation on bioabsorbable scaffolds was feasible with
      extracellular matrix production comparable to vascular-cell derived tissue
      engineered constructs. It appears that MSC represent a promising cell source for
      cardiovascular tissue engineering.

PMID- 12048087
TI  - Short- and long-term results of open heart surgery in patients with abdominal
      solid organ transplant.
AB  - OBJECTIVES: Cardiac disease is a common cause of mortality and morbidity in
      patients with abdominal solid organ transplant. Improvement of the results of
      abdominal organ transplantation has contributed to an increasing pool of patients
      who require open heart surgery. We investigated short- and long-term results of
      open heart surgery in patients with functioning abdominal solid organ
      transplants. METHODS: We retrospectively examined 60 patients (52.5 years in
      average) undergoing coronary artery bypass grafting and/or valve surgery since
      July 1988 after abdominal organ transplantation. There were 22 females (37%).
      They consisted of 46 kidney, nine kidney-pancreas and five liver recipients.
      Cardiac surgery was performed 68.9 months after transplantation. Preoperative
      serum creatinine level was 2.1 mg/dl, and 11 patients (18%) had creatinine level
      more than 3.0 mg/dl. Eleven patients (18%) were operated upon on non-elective
      basis. Twelve patients (20%) were not given stress-dose steroids postoperatively.
      RESULTS: Three patients died early after surgery (5.0%). Twenty-six major
      complications were seen in 17 patients (28%), including deterioration of renal
      function in seven (three patients required temporary hemodialysis), three major
      infections, two bleeding complications, and two strokes. No graft loss was
      encountered. No differences were seen in mortality and morbidity between patients
      with or without stress-dose steroids. Multivariate analysis identified
      cardiopulmonary bypass time (P<0.05) as a risk factor for operative death,
      preoperative creatinine level (P<0.05), cardiopulmonary bypass time (P<0.05) and
      the amount of fresh frozen plasma used (P<0.05) for major complication, non
      elective surgery (P<0.01) for deterioration of renal function. Thirteen patients
      died and five kidney allografts failed late after surgery. Three- and 5-year
      patient and graft survivals were 70.8 and 66.8, 84.5 and 84.5%, respectively.
      Multivariate regression analysis identified female gender (P<0.05), body mass
      index (P<0.001) and non-elective surgery (P<0.001) as risk factors for late
      death, and preoperative creatinine level (P<0.05) for late graft loss.
      CONCLUSIONS: Open heart surgery can be performed with acceptable short- and long
      term results in patients with functioning abdominal transplants. Stress-dose
      steroid may be unnecessary in selected patients. Aggressive use of open heart
      surgery in this patient population to avoid non-elective surgery may further
      improve early and late surgical outcomes.

PMID- 12048088
TI  - Pulmonary preservation with Bretscheider's HTK and Celsior solution in minipigs.
AB  - BACKGROUND: Pulmonary preservation with high potassium/low oncotic pressure Euro
      Collins (EC) solution is associated with endothelial dysfunction and reduced
      surfactant function. We compared two low potassium solutions, histidine
      tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion
      injury. METHODS: In 19 minipigs, the left lung was perfused in situ with cold
      preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started
      after 90 min of warm ischemia. The right pulmonary artery and main bronchus were
      clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h
      of reperfusion. Surfactant activity was determined from the BAL in a pulsating
      bubble surfactometer. RESULTS: Animals in the EC group survived 3.7+/-1.4 h. Six
      Celsior and five HTK treated animals survived the observation period of 7 h
      (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior
      and HTK groups (P<0.001). In EC and HTK animals, the pO(2)/FiO(2) ratio was lower
      (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior
      animals. Surfactant function was impaired after reperfusion in all groups.
      CONCLUSIONS: Compared to EC, HTK solution showed moderate and Celsior distinct
      improvement of post-ischemic pulmonary function. However, surfactant function was
      not well preserved in any group.

PMID- 12048089
TI  - Superior vena cava resection with prosthetic replacement for non-small cell lung
      cancer: long-term results of a multicentric study.
AB  - OBJECTIVES: Superior vena cava (SVC) resection with prosthetic replacement for
      non-small cell lung cancer (NSCLC) is infrequently performed and oncological
      results are unclear. To establish a historical benchmark for this extended
      surgery, we have updated and reviewed data from four international centers.
      METHODS: Data were obtained through retrospective chart review. Prognostic
      factors were analyzed using first univariate techniques and subsequently multiple
      regression (logistic regression). Kaplan-Meier overall survival was calculated
      and prognostic factors examined by log-rank test and the estimation of hazard
      ratios using Cox regression. RESULTS: From 1985 to 2000, 28 patients underwent
      SVC resection with prosthetic replacement for NSCLC. During the same period, 65
      patients underwent partial SVC resection. Induction treatment was performed in
      25% of patients. The resection was done for T involvement in 22 patients (79%),
      and for N2 involvement in the remaining. There were 12 tracheal sleeve
      resections, four pneumonectomies, and 12 lobar or sublobar resections with or
      without bronchoplasty. The median clamping time was 40 min. The median diameter
      of the prosthesis used was No. 14. Pathological examination showed direct SVC
      invasion (T4) in 79% of patients, whereas N2 disease was present in 50% of
      patients. Median intensive care unit and hospital stay were 3 and 20 days,
      respectively. The postoperative morbidity and mortality were 39 and 14%,
      respectively. The overall 5-year probability of survival was 15% (median of 9
      months, range 0-105 months). Patients who underwent partial SVC resection during
      the same period had a significantly higher probability of survival (P=0.03).
      Induction chemotherapy was associated with a significant increase of
      postoperative morbidity in multivariate analysis. None of the potential
      prognostic factors analyzed in multivariate analysis were associated with
      survival, but the type of resection (sleeve pneumonectomy/pneumonectomy) were
      borderline significant. CONCLUSIONS: SVC resection with prosthetic replacement
      should not be considered an absolute contraindication in patients with NSCLC;
      however, the poor oncological results suggest more restrictive and severe
      criteria of patient selection (mediastinoscopy, induction treatment, no
      pneumonectomy, no N2 disease).

PMID- 12048090
TI  - Solitary fibrous tumors of the pleura: clinical characteristics, surgical
      treatment and outcome.
AB  - OBJECTIVE: The aim of this paper is to study clinical characteristics, surgical
      treatment and outcome of patients with solitary fibrous tumor of the pleura
      operated in our institutions in a 20-year period. METHODS: Clinical records of
      all patients operated for solitary fibrous tumors of the pleura between 1981 and
      2000 were reviewed retrospectively. Tumors were classified as malignant in the
      presence of at least one of the following criteria: (1) high mitotic activity;
      (2) high cellularity with crowding and overlapping of nuclei; (3) presence of
      necrosis; (4) pleomorphism; otherwise they were considered as benign. RESULTS:
      Sixty patients (mean age 55 years) were operated in this period. None had
      asbestos exposure. Symptoms were present in 31 cases. Surgical approaches
      included thoracotomy (n=53), video-assisted thoracoscopy (n=6), and median
      sternotomy (n=1). Tumors originated from visceral pleura in 48 cases, from
      parietal, mediastinal or diaphragmatic pleura in seven, two and three cases,
      respectively; their mean diameter was 8.5 cm. Tumors could be resected with their
      implantation basis in 49 patients. In the remaining 11, extended resections were
      performed, including lung parenchyma (lobectomy, n=4, pneumonectomy, n=2),
      osteomuscular chest wall structures (n=2), diaphragm (n=2), and pericardium
      (n=1). Two postoperative deaths (due to myocardial infarction and pulmonary
      embolism, respectively) occurred. Tumors were pathologically benign in 38 cases
      and malignant in 22 cases. Mean follow-up was 88 months. Resection was complete
      in all the patients with benign tumors and no recurrence occurred. Resection was
      considered as complete in 21/22 malignant tumors. Local recurrence was observed
      in two cases. Both could be successfully managed by iterative exeresis (no
      extended resection had been initially performed). Metastatic disease (responsible
      for patient's death) was observed following the only incomplete resection.
      Actuarial 5- and 10-year survival rates were 97% for benign tumors and 89% for
      malignant ones. CONCLUSIONS: Surgical resection provided cure in all the patients
      with benign tumors. As insufficiency of exeresis is associated with all
      recurrences in malignant tumors, completeness of resection is in our experience
      the best prognostic factor in these forms.

PMID- 12048091
TI  - VATS is an adequate oncological operation for stage I non-small cell lung cancer.
AB  - OBJECTIVES: This study was designed to determine the long-term prognosis of video
      assisted thoracic surgery (VATS) vs. open lung resections for patients with
      pathological stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      The medical records of all patients who underwent lung resection for a
      pathological stage I NSCLC were reviewed for the period from 1990 to 1999, by
      screening of a database into which data were entered prospectively. There were
      511 patients (430 males and 81 females) whose age averaged 63+/-10 years who
      underwent 515 lung resections. Our VATS experience began in 1993 with selected
      stage I patients, and since that date an average of one patient on four was
      managed with VATS. Lung resections consisted of 25 wedge resections or
      segmentectomies (seven VATS), 390 lobectomies (92 VATS), 19 bilobectomies (one
      VATS) and 81 pneumonectomies (ten VATS). Lymph node dissection was performed in
      all cases. RESULTS: There were significantly more females (P=0.01) and
      adenocarcinoma (P=0.02) in the VATS group (n=110) when compared to the open group
      (n=405). Tumour size averaged 4+/-2 cm in the open group and 3+/-2 cm in the VATS
      group (P=0.04). The distribution of T1/T2 tumours was 97/308 and 50/60,
      respectively (P=0.0001). At follow-up, cancer recurrence could be documented in
      117 patients, with no difference of incidence between the two groups (22.5 vs.
      24.5%; P=0.64). Estimated Kaplan-Meier 5-year survival rates, including the
      operative mortality as well as any cancer-related and unrelated death, were 62.8%
      (confidence interval (CI): 56.8-68.7%) vs. 62.9% (CI: 51.4-74.4%), respectively
      (P=0.60). The advent of VATS did not influence the patients' survival: 5-year
      survival rate was 63.9% (CI: 55.3-72.5%) for the period from 1990 to 1992, and
      58.8% (CI: 51.7-65.9%) for the period from 1993 to 1999 (P=0.65). Subgroups
      survival analysis according to the T status did not show any statistically
      significant difference between the two groups. CONCLUSIONS: VATS lung resection
      with lymph node dissection achieved a 5-year survival similar to that achieved by
      the conventional approach. VATS is a valuable option for the management of
      selected patients with an early-stage NSCLC.

PMID- 12048092
TI  - Therapeutic strategy in patients with non-small cell lung cancer associated to
      satellite pulmonary nodules.
AB  - OBJECTIVES: In patients with non-small cell lung cancer (NSCLC) the presence of
      satellite metastatic nodules may be considered a contraindication to surgical
      treatment. The use of spiral computed tomography (CT) scan has improved the
      accuracy of the diagnostic assessment of pulmonary diseases, but has also led to
      the detection of a consistent number of indeterminate satellite lesions.
      Obtaining a differential diagnosis of these lesions is extremely important in
      defining the therapeutic strategy. The aim of the study was to assess the
      characteristics of satellite nodules in patients with NSCLC and to examine the
      diagnostic and therapeutic approach used in the presence of indeterminate
      satellite lesions. METHODS: From November 1995 to February 2001, 29 patients
      (mean age 64 years) who underwent surgery for NSCLC had indeterminate satellite
      pulmonary lesions at the preoperative spiral CT scan. A differential diagnosis of
      the nodules was obtained by histological examination in 27 patients and by follow
      up (62 and 64 months, respectively) in two patients. Positron emission tomography
      (PET) scan was selectively performed in the preoperative evaluation. RESULTS:
      Thirty-two satellite nodules were analyzed in the group of 29 patients. The size
      of the lesions varied from 2 to 15 mm (mean 8mm). The nodules were ipsilateral to
      the primary tumor in 25 patients and contralateral in four. They were benign in
      22 cases and malignant in ten (metastases from NSCLC in seven patients and second
      primary lung cancer in three). Nodules with a size equal to or less than 5mm were
      more frequently benign. Patients with stage III tumors had a higher incidence of
      malignant satellite nodules in comparison to earlier stages, although the data
      did not reach statistical significance. PET scan correctly differentiated benign
      and malignant satellite nodules in six patients. CONCLUSIONS: Obtaining a
      differential diagnosis of indeterminate pulmonary nodules associated to NSCLC is
      of great importance in defining the therapeutic strategy. The results of this
      study show that indeterminate satellite lesions may be benign or represent a
      second primary lung cancer, and should not therefore be considered a
      contraindication to surgical exploration when a preliminary differential
      diagnosis by other means cannot be obtained.

PMID- 12048093
TI  - Small cell lung carcinoma (SCLC): the angiogenic phenomenon.
AB  - OBJECTIVES: Tumor angiogenesis, expressed by the microvessel count (MVC), and its
      mediators (i.e. vascular endothelial growth factor) significantly correlate with
      metastases in surgically treated non-small cell lung carcinoma/cancer (NSCLC).
      SCLC is rarely treated by surgery, as a consequence, few specimens are available
      to perform a biological characterization. We reviewed our experience in the
      surgical treatment of SCLC with particular reference to the angiogenetic
      expression and its correlation to the stage of disease and prognosis. METHODS: We
      retrospectively investigated a homogenous cohort of 87 patients with SCLC, who
      were primarily operated on and then underwent adjuvant chemotherapy between 1980
      and 1998. Their median age was 62 years (range 34-73). All the patients were
      completely staged. The surgical procedures included: 32 pneumonectomies and 55
      lobectomies. There were 46 N0, 17 N1 and 24 N2-disease. The adjuvant chemotherapy
      consisted of four to six courses of cyclophosphamide, epidoxorubicine and
      etoposide. The MVC was determined highlighting the microvessels with anti-CD34
      monoclonal antibodies. Immunostaining for VEGF was performed using the ABC method
      with anti-VEGF monoclonal antibodies. The p53 protein expression was assessed by
      NCL-DO7 anti-p53 monoclonal antibody. RESULTS: With a median follow-up of 109.6
      months (range 25-238), 37 patients are alive and well, two are alive with
      systemic metastases. Forty-four patients died of local (n=5) or systemic (n=39)
      relapse, while four patients died from other causes. The median MVC was 59 (range
      18-145). Among the clinico-pathological parameters, metastatic nodal-involvement
      (P=0.002) and advanced stage of disease (P=0.005) were associated with a worse
      overall survival (OS). MVC and VEGF protein expression significantly affected the
      survival (P<0.001 and P=0.0008, respectively). No statistical association was
      found between p53 alterations and OS as well as no association was found among
      p53 alterations, MVC and VEGF expression. On multivariate analysis only the VEGF
      expression (P=0.003) was an independent prognostic factor. CONCLUSIONS:
      Angiogenesis plays a role in the metastatic process of the SCLC as well as NSCLC.
      SCLC has a higher vascularization than NSCLC as results from the higher number of
      microvessels; however, tumor angiogenesis tested by the MVC and the VEGF protein
      expression correlates with the prognosis also in SCLC. SCLC may be an ideal field
      to test new antiangiogenic drugs associated to chemotherapy.

PMID- 12048094
TI  - Pulmonary metastases: can accurate radiological evaluation avoid thoracotomic
      approach?
AB  - OBJECTIVES: To evaluate the effectiveness of radiological assessment (high
      resolution CT (HRCT), helical CT (HCT) scan) of lung metastases and to verify if
      a complete manual exploration by thoracotomy is necessary. MATERIALS AND METHODS:
      From 1/96 to 1/00, 166 consecutive patients presenting with lung metastases were
      treated. Preoperative CT scan (HRCT in 78 patients, group A; HCT in 88 patients,
      group B) to assess the number, size and location of the lesions (slice thickness
      5 mm; reconstruction interval 3-5 mm) was always performed. All patients
      underwent axillary thoracotomy (staged when lesions were bilateral); accurate
      palpation of the lung parenchyma was always performed to identify any undetected
      lesion. Non-metastatic lesions were excluded. RESULTS: We performed 356 wedge
      resections in 161 patients (113 monolateral, 70.2%; 48 bilateral, 29.8%) and five
      lobectomies. In group A, primary neoplasm was epithelial in 44 patients, sarcoma
      in 26 and germ cell in eight, and in group B, epithelial in 61 patients, sarcoma
      in 20 and germ cell in seven. Three hundred and sixty-one histologically proven
      metastases were resected (188 in group A and 173 in group B). HRCT correctly
      identified 142/188 lesions (sensitivity 75%); HCT revealed 142/173 metastases
      (sensitivity 82.1%). Sensitivity for lesions less than 6 mm in maximum diameter
      was 48% (30/58 false negative) in group A and 61.5% (20/52 false negative) in
      group B. CONCLUSIONS: The sensitivity of HCT exceeds that of HRCT. However,
      complete manual exploration by thoracotomy remains the procedure of choice for
      patients undergoing pulmonary metastasectomy, because of limitation in
      preoperative radiological assessment of lung lesions smaller than 6 mm.

PMID- 12048095
TI  - Is intercostal block for pain management in thoracic surgery more successful than
      epidural anaesthesia?
AB  - OBJECTIVE: Currently epidural anesthesia is the gold standard for postoperative
      pain management in thoracic surgery. In a prospective randomised study, the
      effect of an intercostal nerve block applied at the end of the operation was
      compared to that of epidural anesthesia. METHODS: Thirty patients undergoing
      thoracotomy were randomised to each group. Patients with resection of the
      parietal pleura, rib resection and rethoracotomy were excluded from the study.
      Both groups received non-steroidal anti-inflammatory drugs every 8h as a baseline
      analgesic medication and were allowed to ask for supplemental subcutaneous opiate
      injection, limited to four injections per day. The patients in the epidural
      catheter group (group I) were provided with a motor pump allowing continuous
      infusion of bupivacain 0.125% and 2mg fentanyl/ml at a dosage of 6-10 ml per
      hour, dependent on the pain level over a period of 5 days. The patients of the
      second group (group II) received an intercostal nerve block at the end of the
      operation reaching from the third to the ninth intercostal space with 20 ml 0.5%
      bubivacaine. Pain was evaluated with a pain score ranging from 1 (no pain) to 10
      (worst pain) twice daily in relaxed position and during physical activity like
      coughing. On the fifth postoperative day, the patients were asked specific
      questions concerning the subjective pain experience. Costs of both treatments
      were calculated. Mean pain values and costs of both groups were compared by t
      tests for independent samples. A P value of less than 0.05 was considered
      significant. RESULTS: Eighteen male and 12 female patients, aged between 35 and
      71 years (mean 59) were included in the study. Nineteen patients had lobectomy,
      five bilobectomy, two decortication and three wedge resection. There were 22
      right sided and eight left sided procedures. In group I, the mean pain score on
      the operation day was 3.95 in relaxed position and 6.33 during physical activity
      like coughing. The mean pain score during the following 4 days was 2.19 in
      relaxed position and 4.28 with activity. Three patients required additional
      subcutaneous opiate injection. In group II, the mean score on the operation day
      was 2.0 in relaxed position and 3.5 during activity. The mean pain score during
      the next 4 days was 2.84 in relaxed position and 5.65 with activity. Twelve
      patients received subcutaneous opiates. In both groups, no complications were
      observed. COSTS: The costs for treatment of one patient was 105 in group I and 33
      in group II. Patients' satisfaction was equal in both groups, there were no
      differences in terms of outcome and recovery. CONCLUSION: Pain management by
      intercostal block was superior during the first 24h after surgery whereas on the
      second day after surgery pain control was significantly better achieved by the
      epidural catheter in relaxed position. A combination of both forms of anaesthesia
      seems to be an ideal pain management in patients undergoing thoracic surgery.

PMID- 12048096
TI  - Cardiac papillary fibroelastoma.

PMID- 12048097
TI  - 'Shunt shuffle'-a simple technique of introducing intracoronary shunts for off
      pump coronary artery bypass.
AB  - Intracoronary shunting is a useful method for maintaining distal perfusion as
      well as providing a bloodless field during off-pump coronary revascularization.
      Intracoronary shunts require insertion of both ends through a limited
      arteriotomy, which sometimes can be troublesome. We describe the 'shunt shuffle'
      as a simple technique, which allows rapid, atraumatic and easy insertion of
      intracoronary shunts.

PMID- 12048098
TI  - Repair of aorto-right ventricular tunnel with pulmonary stenosis and an anomalous
      origin of the left coronary artery.
AB  - A 5-month-old infant with aorto-right ventricular tunnel, pulmonary stenosis and
      a sole supply of the left coronary artery from the tunnel underwent closure of
      the ventricular end of the tunnel, subsequent to balloon pulmonary valvuloplasty.
      Care was taken not to obstruct the aortic end of the tunnel in order to maintain
      the left coronary artery perfusion.

PMID- 12048101
TI  - A novel dissemination pathway of hydatid cyst.

PMID- 12048099
TI  - Ectopic ACTH-producing tumors of the chest and octreotide scintigraphy.

PMID- 12048103
TI  - Palliative surgery for malignant pleural mesothelioma.

PMID- 12048106
TI  - Molecular dissection of dopamine receptor signaling.
AB  - The use of genetically engineered mice has provided substantial new insights into
      the functional organization of the striatum. Increasing evidence suggests that
      specific genes expressed within the striatum contribute to its functional
      activity. We studied the dopamine (DA) D1 receptor gene and one of its downstream
      targets, the transcription factor c-Fos. We have evaluated the functional
      interaction between the D1 and D2 DA receptor subtypes at the cellular and
      behavioral levels. Our results show that haloperidol, a DA D2-class receptor
      antagonist, activates c-Fos predominantly in enkephalin-positive striatal
      neurons, which project to the globus pallidus and are thought to mediate motor
      inhibition. Deletion of the DA D1 receptor increased the responsiveness of
      enkephalin neurons to haloperidol, in that haloperidol-induced increases in c-Fos
      and catalepsy were enhanced in D1 receptor knockout mice. These results suggest a
      functionally opposing role of the D1 receptor against the D2 DA-class receptors
      in the striatum.

PMID- 12048107
TI  - Polymer hydrogels usable for nervous tissue repair.
AB  - The implantation of non-resorbable biocompatible polymer hydrogels into defects
      in the central nervous system can reduce glial scar formation, bridge the lesion
      and lead to tissue regeneration within the hydrogel. We implanted hydrogels based
      on crosslinked poly hydroxyethyl-methacrylate (pHEMA) and poly N-(2
      hydroxypropyl)-methacrylamide (pHPMA) into the rat cortex and evaluated the
      cellular invasion into the hydrogels by means of immunohistochemical methods and
      tetramethylammonium diffusion measurements. Astrocytes and NF160-positive axons
      grew similarly into both types of hydrogels. We found no cell types other than
      astrocytes in the pHEMA hydrogels. In the pHPMA hydrogels, we found a massive
      ingrowth of connective tissue elements. These changes were accompanied by
      corresponding changes in the extracellular space volume fraction and tortuosity
      of the hydrogels.

PMID- 12048108
TI  - Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor
      profile suggestive of vulnerability to excitotoxicity.
AB  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors
      mediate excitatory neurotransmission in the central nervous system, and contain
      combinations of four subunits (GluR1-4). We developed a GluR3-specific monoclonal
      antibody and quantified the cellular distribution of GluR3 in rat hippocampus.
      GluR3 immunoreactivity was detected in all pyramidal neurons and most
      interneurons. In addition, we found a subset of parvalbumin (PV)-containing
      interneurons in the hippocampus and neocortex that was notable for its intense
      GluR3 immunoreactivity and lack of GluR2 immunoreactivity. Such an expression
      pattern of AMPA receptor subunits is likely to make these interneurons
      selectively vulnerable to excitotoxicity.

PMID- 12048109
TI  - Developmental expression of three different prepro-GnRH (gonadotrophin-releasing
      hormone) messengers in the brain of the European sea bass (Dicentrarchus labrax).
AB  - In this study, we have analyzed the ontogenic expression of three gonadotrophin
      releasing hormones (GnRH) systems expressed in the brain of a perciform fish, the
      European sea bass, using in situ hybridization. The riboprobes used correspond to
      the GnRH-associated peptide (GAP) coding regions of the three prepro-GnRH cDNAs
      cloned from the same species: prepro-salmon GnRH, prepro-seabream GnRH and prepro
      chicken GnRH II. On day 4 after hatching, the first prepro-chicken GnRH-II mRNA
      expressing cells appeared in the germinal zone of the third ventricle. They
      increased in number and size from 10 to 21 days, reaching at day 30 their adult
      final position, within the synencephalic area, at the transitional zone between
      the diencephalon and the mesencephalon. First prepro-salmon GnRH mRNA-expressing
      cells became evident on day 7 arising from the olfactory placode and migrating
      towards the olfactory nerve. On day 10, this cell group reached the olfactory
      bulb, being evident in the ventral telencephalon and preoptic area from days 15
      and 45, respectively. Weakly labeled prepro-seabream GnRH mRNA-expressing cells
      were first detected at 30 days in the olfactory area and ventral telencephalon.
      On day 45, prepro-seabream GnRH mRNA-expressing cells were also present in the
      preoptic region reaching the ventrolateral hypothalamus on day 60. The results
      obtained in sea bass indicate that sGnRH and sbGnRH cells have a common origin in
      an olfactory primordium suggesting that both forms might arise from a duplication
      of a single ancestral gene, while cGnRH-II cells develop from a synencephalic
      primordium.

PMID- 12048110
TI  - Sex differences in the densities of alpha 2-adrenergic receptors in the song
      control system, but not the medial preoptic nucleus in zebra finches.
AB  - In songbirds, song is regulated by a specialized group of brain nuclei known as
      the song system. Other aspects of courtship, such as male sexual interest in a
      female, are likely regulated by the medial preoptic nucleus (POM). The song
      control system and the POM are rich in norepinephrine, which appears to regulate
      courtship behaviors, including song. Zebra finches (Taeniopygia guttata) exhibit
      an extreme sexual dimorphism in song behavior; males sing, primarily to attract
      or maintain mates, and females do not. We explored possible sex differences in
      the distribution and density of the alpha(2)-adrenergic receptors in the song
      system and POM of zebra finches. Receptors were labeled with the selective
      ligand, [(3)H] RX821002, via autoradiographic procedures. In males, dense
      alpha(2)-receptors were observed in the song system (Area X, the high vocal
      center (HVc), the lateral portion of the magnocellular nucleus of the anterior
      neostriatum, and the robust nucleus of the archistriatum). In contrast, in
      females neither the lateral portion of the magnocellular nucleus of the anterior
      neostriatum nor the HVc could be identified based on alpha(2)-receptor binding.
      Females lack Area X and indeed differential alpha(2)-binding was not observed
      within the female lobus parolfactorius. The robust nucleus of the archistriatum
      contained less dense alpha(2)-binding in females compared to males. Alpha(2)
      binding in the POM was similar in males and females. The dimorphism in alpha(2)
      binding in nuclei of the song system likely relates to the dimorphism in song
      behavior observed in male and female zebra finches.

PMID- 12048111
TI  - The intralaminar nuclei assigned to the medial pain system and other components
      of this system are early and progressively affected by the Alzheimer's disease
      related cytoskeletal pathology.
AB  - The intralaminar nuclei of the human thalamus are integrated into the ascending
      reticular activating system and into limbic, oculomotor and somatomotor loops. In
      addition, some of them also represent important components of the medial pain
      system. We examined the occurrence and severity of the Alzheimer's disease (AD)
      related cytoskeletal pathology and beta-amyloidosis in the seven intralaminar
      nuclei (central lateral nucleus, CL; central medial nucleus, CEM; centromedian
      nucleus, CM; cucullar nucleus, CU; paracentral nucleus, PC; parafascicular
      nucleus, PF; subparafascicular nucleus, SPF) in 27 autopsy cases at different
      stages of the cortical neurofibrillary pathology (cortical NFT/NT-stages I-VI)
      and beta-amyloidosis (cortical phases 1-4). The CEM, CL, PF, and SPF are slightly
      affected at stage II (corresponding to preclinical AD). They are markedly
      involved at stages III and IV (i.e. incipient AD) and severely affected at stages
      V and VI (i.e. clinical AD). In the PC and CU, the cytoskeletal pathology is mild
      at stage III, marked at stage IV, and severe at stages V-VI, whereas the CM is
      only mildly affected at stages IV-VI. In all of the intralaminar nuclei, deposits
      of the protein beta-amyloid occur for the first time during the final phase of
      cortical beta-amyloidosis. Functionally, the cytoskeletal pathology encountered
      in the intralaminar nuclei may contribute to the memory and affective symptoms,
      attention deficits, and dysfunctions related to horizontal saccades and smooth
      pursuits seen in AD patients. Equally important, however, are the findings that
      the cytoskeletal pathology developing within the intralaminar nuclei assigned to
      the medial pain system (CEM, CL, CU, PC, PF) as well as within other components
      of this system begins already during the preclinical or incipient phases of AD.
      Given this fact, the question arises as to whether non-discriminative aspects
      mediated by the medial pain system could be employed to identify individuals in
      the very earliest stages of AD.

PMID- 12048112
TI  - Expression of glycogen synthase kinase-3 isoforms in mouse tissues and their
      transcription in the brain.
AB  - Glycogen synthase kinase-3alpha and -3beta (GSK-3alpha and -3beta) are multi
      substrate, serine/threonine-specific kinases that can phosphorylate microtubule
      associated protein tau and other neuronal proteins. In this study, the expression
      level and mRNA distribution of two GSK-3 isoforms, GSK-3alpha and -3beta in mice
      were investigated. Northern blot analyses indicated that GSK-3alpha mRNA is
      encoded by a 2.5-kb transcript in adult tissues, whereas a 4.1-kb transcript was
      found in neonatal tissues. The GSK-3beta mRNA is encoded by a 1.6-kb transcript
      in the testis and a 7.6-kb transcript in the brain, and in many other adult
      tissues, but not neonatal tissues. Western blot analyses demonstrated that GSK
      3beta protein was mainly expressed in the brain and heart, whereas GSK-3alpha was
      highly expressed in the brain, heart, and testis. A non-radioactive in situ
      hybridization study using specific digoxigenin-labeled RNA probes showed that GSK
      3alpha and -3beta mRNAs were found in many brain regions, and were especially
      abundant in the hippocampus, cerebral cortex, and the Purkinje cells of the
      cerebellum. This implies the importance of GSK-3alpha and -3beta for brain
      function. The differential expression of GSK-3alpha and -3beta mRNAs as well as
      proteins in other tissues indicate that they play different roles in cellular
      functions and the developmental process.

PMID- 12048116
TI  - Cellular cholesterol flux studies: methodological considerations.
AB  - Reverse cholesterol transport (RCT) is the process in which peripheral cells
      release cholesterol to an extracellular acceptor such as high-density lipoprotein
      (HDL) which then mediates cholesterol delivery to the liver for excretion. RCT
      represents a physiological mechanism by which peripheral tissues are protected
      against excessive accumulation of cholesterol. The first step in RCT is the
      interaction of the cell with lipoprotein particles, a process that results in
      both the cellular uptake and release of cholesterol. The various components of
      this cholesterol flux can be viewed as efflux, influx and net flux. Experimental
      protocols for measuring each of these components of cholesterol flux are very
      different, and a number of considerations are required to design experimental
      approaches for the quantitation of flux parameters. Although many flux studies
      have been conducted in the past, the recent discoveries of the scavenger receptor
      B1 (SR-B1) and ATP binding cassette 1 (ABCA1), which mediate the movement of
      cholesterol between cells and extracellular acceptors, has led to increased
      interest in studies of cellular cholesterol flux. The aim of this review is to
      present a discussion of the methodological considerations that should be
      evaluated during the design and analysis of cellular cholesterol flux
      experiments.

PMID- 12048117
TI  - Induction of cyclooxygenase-2 and enhanced release of prostaglandin E(2) and I(2)
      in human endothelial cells by engagement of CD40.
AB  - OBJECTIVES: The hypothesis was tested that CD40-CD154 interaction is involved in
      the induction of cyclooxygenase-2 and the release of prostanoids in human
      endothelial cells. METHODS AND RESULTS: In a coculture model of human endothelial
      cells and a transfected CD154 positive cell line, engagement of CD40 on
      endothelial cells dramatically increased the synthesis of prostacyclin,
      prostaglandin E(2) and thromboxane A(2). This upregulation was mediated through
      an induction of cyclooxygenase-2 (Cox-2), as it was blocked by Cox-2-selective
      inhibitors. Western blot analysis demonstrated that Cox-2 protein was markedly
      increased in endothelial cells following CD40 engagement, an effect that was
      inhibited by pretreatment of cells with an anti-CD154 antibody. CONCLUSION: The
      data indicate that signaling via CD40 constitutes a major pathway in human
      endothelial cells for the induction of Cox-2 and release of prostanoids. The CD40
      Cox-2 axis thus may represent an important pathway for initiating or maintaining
      an inflammatory process at the vessel wall.

PMID- 12048118
TI  - Increased macrophage glutathione content reduces cell-mediated oxidation of LDL
      and atherosclerosis in apolipoprotein E-deficient mice.
AB  - We used the apolipoprotein E deficient (apo e-/-) mice to analyze the role of
      macrophage reduced glutathione (GSH) content in cell-mediated oxidation of LDL
      and in atherosclerotic lesion development. Apo e-/- mice were supplemented with L
      2-oxo-4-thiazolidin carboxylate (OTC, which supplies cysteine residues, 500
      mg/kg/day), or with buthionine sulfoximine (BSO, a specific inhibitor of GSH
      synthesis, 400 mg/kg/day) for 6 weeks. Then mouse peritoneal macrophages (MPM)
      and the mice aortas were collected. MPM from apo e-/- mice contained decreased
      GSH levels (by 58%), and a four-fold increased lipid peroxides content compared
      to control macrophages from C57BL6 mice. These MPM demonstrated increased
      capability to release superoxide anions and to oxidize LDL in comparison to
      control MPM. OTC supplementation resulted in a 26% increase in macrophage GSH,
      paralleled by a 25% reduction in cellular lipid peroxides content. Decrement by
      30% in superoxide anion release and LDL oxidation by MPM, and also in the
      atherosclerotic lesion size by 25%, was found in the OTC-treated mice, compared
      to placebo-treated apo e-/- mice. In contrast, in BSO-treated mice MPM a further
      depletion of cellular GSH by 22% was found, paralleled by a two-fold increase in
      lipid peroxides content, and a 41% increased superoxide anion release and cell
      mediated LDL oxidation, compared to placebo-treated apo e-/- mice MPM. Most
      important, BSO supplementation to apo e-/- mice caused a 59% increase in the
      atherosclerotic lesion area. An additional way to increase cellular GSH content
      was the use of dietary antioxidants. Vitamin E (40 mg/kg/day) or the isoflavan
      glabridin (25 microg/kg/day) administration for 2 months to apo e-/- mice
      resulted in the accumulation of these antioxidants in their MPM, and increased
      MPM GSH content by 24 and 80%, respectively. MPM lipid peroxides content was
      reduced by 31 or 60% upon vitamin E or glabridin supplementation, paralleled by a
      30 or 60% decrease in cell-mediated oxidation of LDL, respectively. Finally, a
      significant inverse correlation (R=0.83) was found between macrophage GSH content
      and cell-mediated oxidation of LDL. We conclude that enrichment in vivo of
      macrophages with GSH, significantly decreases cellular oxidative stress, leading
      to reduced capability of the macrophages to oxidize LDL, and hence GSH may
      attenuate the development of atherosclerosis.

PMID- 12048119
TI  - Gender and hormonal status affect the regulation of hepatic cholesterol 7alpha
      hydroxylase activity and mRNA abundance by dietary soluble fiber in the guinea
      pig.
AB  - Dietary soluble fiber (SF) consistently lowers plasma LDL cholesterol (LDL-C)
      concentrations, however, secondary mechanisms governing this reduction are not
      completely defined. Moreover, these mechanisms appear to differ with gender.
      Male, female and ovariectomized (to mimic menopause) guinea pigs were used to
      assess effects of gender, hormonal status and SF on activity and expression of
      hepatic cholesterol 7alpha-hydroxylase (CYP7). Diets were identical except for
      fiber source (control 10% cellulose, SF 5% psyllium/5% pectin). SF intake
      resulted in 44% lower plasma total cholesterol, 51% lower plasma LDL-C and 22%
      lower plasma triacylglycerol (TAG) concentrations. However, ovariectomized guinea
      pigs fed either the control or SF diets, had the highest plasma LDL-C and TAG
      levels (P<0.01). SF altered hepatic cholesterol metabolism by effectively
      reducing hepatic free cholesterol, TAG and microsomal free cholesterol, while
      activity of CYP7, the rate-limiting enzyme of cholesterol catabolism, was up
      regulated. Hepatic CYP7 mRNA abundance paralleled the increase in enzyme
      activity. Ovariectomized guinea pigs had lowest activity and expression of
      hepatic CYP7 even after intervention with SF. These results suggest that
      induction of hepatic CYP7 activity may account, in large part, for the
      hypocholesterolemic effect of SF. Gender and hormonal status influence metabolic
      responses to dietary SF with estrogen deprivation leading to the most detrimental
      lipid profile.

PMID- 12048120
TI  - Rho/Rho-kinase is involved in the synthesis of tissue factor in human monocytes.
AB  - Monocytes and macrophages synthesize tissue factor (TF) which plays a role in
      thrombogenicity in coronary artery disease. This study was conducted to
      investigate the effect of Rho/Rho-kinase inhibition on the synthesis of TF in
      cultured human monocytes. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors (statins), C3 exoenzyme and Rho-kinase inhibitors were added
      to isolated peripheral blood monocytes and the synthesis of TF was assessed by
      reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting and
      immunohistochemistry. Rho activity was determined by measuring the GTP-bound form
      of Rho A. Cerivastatin and pravastatin reduced the levels of TF antigen and mRNA.
      The suppressive effect of statins on TF synthesis was reversed by
      geranylgeranylpyrophosphate (GGPP) and the restoring effect of GGPP was
      eliminated by C3 exoenzyme and Y-27632. Pravastatin decreased the activity of Rho
      A, suggesting that the suppression of TF synthesis by statins is mediated via
      inhibition of the geranylgeranylation of Rho. Moreover, inhibition of Rho and Rho
      kinase downregulated the synthesis of TF. Our results suggest that Rho/Rho-kinase
      signaling is involved in the synthesis of TF in human monocytes and that
      inhibition of Rho/Rho-kinase may be useful for treating thrombogenicity in
      coronary artery disease.

PMID- 12048121
TI  - Analysis of apolipoprotein A-I, lecithin:cholesterol acyltransferase and
      glucocerebrosidase genes in hypoalphalipoproteinemia.
AB  - Hypoalphalipoproteinemia (HALP) is a dyslipidemia characterized by low HDL
      cholesterol (HDL-C) levels with important genetic contribution. However, no
      common genetic mutations have been found to be associated with this disorder. We
      screened the promoter and coding sequence of apolipoprotein (apo) A-I and
      lecithin:cholesterol acyltransferase (LCAT) genes and the 5' apo C-III region by
      SSCP and heteroduplex analysis, and DNA sequencing in 66 unrelated subjects with
      recurrent low HDL-C levels. We also analyzed the N370S and L444P variants, in the
      glucocerebrosidase (GBA) gene by restriction fragment analysis. Three mutations
      in the apo A-I gene (L144R, W108R, g.1833C>T) and 3 mutations in the LCAT gene
      (S208T, I178T, IVS3-23C>A) were detected, in six heterozygous subjects. In
      addition, a novel polymorphic site in LCAT gene (g.4886C>T) has been identified.
      Allelic frequencies of polymorphisms g.(-636)C>A, g.(-625)G>A, g.(-620)T>del, g.(
      479C>T and g.(-452)T>C, located upstream of the apo C-III gene, were in normal
      range, and no other mutation was found in this region. Two HALP subjects were
      found to carry the N370S mutation at GBA locus. In conclusion, 12% of HALP
      subjects were found to carry mutations in apo A-I, LCAT, or GBA genes, which
      could explain this phenotype. Our results confirm the molecular, genetic and
      phenotypic heterogeneity of HALP.

PMID- 12048122
TI  - Simvastatin, an HMG-CoA reductase inhibitor, induces the synthesis and secretion
      of apolipoprotein AI in HepG2 cells and primary hamster hepatocytes.
AB  - Clinical studies have recently suggested that statin treatment may beneficially
      elevate plasma concentrations of high density lipoprotein (HDL)-cholesterol in
      patients with hyperlipidemia. Here, we have investigated the effect of a potent
      inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase on the
      synthesis and secretion of apolipoprotein AI (apoAI) in two model systems, HepG2
      cells and primary hamster hepatocytes. Cultured cells were incubated with
      different doses of simvastatin (0.1-10 microM) for a period of 18 h. A dose
      dependent increase in synthesis and secretion of apoAI was observed in both cell
      types. There was a significant increase in the synthesis of apoAI in HepG2 cells
      (44.3+/-12.1%), and hamster hepatocytes (212+/-2%) after treatment with 10 microM
      of the statin. The increase in apoAI synthesis appeared to result in a higher
      level of apoAI secreted into the culture media in both cell types (49.2+/-7.8% in
      HepG2, 197+/-0.2% in hamster hepatocytes). ApoAI mRNA levels were also
      significantly increased in both cell types in response to statin treatment.
      Control experiments with transferrin confirmed specificity of the effect on apoAI
      secretion. Analysis of a density fraction containing HDL particles in culture
      media revealed an increase in HDL-associated apoAI of 94.3+/-2.1% in HepG2 cells
      and 27.0+/-0.03% in hamster hepatocytes following 10 microM simvastatin
      treatment. Comparative studies of simvastatin and lovastatin indicated a
      differential ability to induce apoAI synthesis and secretion, with simvastatin
      having a more significant effect. Thus, acute statin treatment of cultured
      hepatocytes (transformed as well as primary) resulted in a significant
      upregulation of apoAI mRNA and apoAI synthesis, causing oversecretion of apoAI
      and HDL extracellularly. The stimulatory effect on apoAI synthesis and secretion
      may thus explain the clinical observation of an elevated plasma HDL-cholesterol
      level in hyperlipidemic patients treated with certain statins.

PMID- 12048123
TI  - Hypercholesterolaemia and circulating levels of CXC chemokines in apoE*3 Leiden
      mice.
AB  - Hyperlipidaemia may accelerate the development of atherosclerosis by enhancing
      the expression of chemokines by cells within the arterial wall. Chemokines of the
      CC subfamily are clearly implicated in atherogenesis; however, recent reports
      suggest that CXC chemokines may play a hitherto unrecognised role in monocyte
      recruitment into atheromatous lesions expressing these molecules. Here, we
      examine whether circulating levels of CXC chemokines may reflect the pathogenic
      changes occurring during early atherogenesis. ApoE*3 Leiden mice developed marked
      hypercholesterolaemia, and early Type I 'fatty streak' lesions, following
      consumption of an atherogenic diet high in saturated fat and cholesterol, and
      containing sodium cholate, for up to 4 weeks. By contrast, their non-transgenic
      littermates (C57BL/6J) exhibited a much less pronounced hypercholesterolaemia and
      did not develop fatty streak lesions, when fed the same diet. Under these
      conditions, serum concentrations of CXC chemokines, KC and Macrophage
      Inflammatory Protein-2 (MIP-2) were significantly (P<or=0.0005) elevated in
      apoE*3 Leiden mice consuming HFC/C diet, compared with apoE*3 Leiden mice
      consuming a chow diet. Further, serum concentrations of KC were significantly
      (P<0.02) higher at 4 weeks in apoE*3 Leiden mice fed HFC/C diet compared with
      their non-transgenic littermates consuming the same diet. Expression of KC mRNA
      was detected in both aortic and hepatic tissues of apoE*3 Leiden mice, and the
      non-transgenic controls. Thus, hypercholesterolaemia is associated with elevated
      serum concentrations of CXC chemokines, KC and MIP-2 that probably reflect
      chronic inflammation during atherogenesis.

PMID- 12048124
TI  - Taurine suppresses development of atherosclerosis in Watanabe heritable
      hyperlipidemic (WHHL) rabbits.
AB  - While the hypocholesterolemic effects of taurine have extensively been studied
      using experimental animals, the anti-atherosclerotic effects of taurine have been
      given less attention. We examined the effect of taurine on atherosclerotic
      lesions in Watanabe heritable hyperlipidemic (WHHL) rabbits. Treatment of WHHL
      rabbits with taurine (0.3% in drinking tap water) for 24 weeks decreased aortic
      lesions by 31%, estimated as intimal thickening. Taurine significantly decreased
      cholesteryl ester content of aortic arch, thoracic aorta, and abdominal aorta by
      35, 43, and 54%, respectively. Concomitantly, activity of acyl-CoA:cholesterol
      acyltransferase (ACAT), an enzyme responsible for cholesterol esterification, was
      also significantly decreased. Immunohistochemical analysis revealed decreased
      macrophages in the intima of taurine-treated rabbits. Taurine had no apparent
      effect on blood pressure and serum cholesterol levels. Contents of thiobarbituric
      acid reactive substances (TBARS), a marker of lipid peroxidation, was reduced in
      serum and aorta by 29 and 50%, respectively, when taurine was ingested. In
      addition, LDL from taurine-treated rabbits was resistant to copper-induced
      oxidative modification. These results revealed that taurine prevents development
      of atherosclerosis and that the anti-atherosclerotic effects of taurine are
      independent of serum cholesterol levels. The anti-oxidant action of taurine may
      be involved in inhibiting atherosclerosis in these rabbits.

PMID- 12048125
TI  - Macrophages, myofibroblasts and neointimal hyperplasia after coronary artery
      injury and repair.
AB  - Macrophages participate in the restenosis process through the release of
      cytokines, metalloproteinases and growth factors. Studies of peritoneal
      granulation tissue suggest that macrophages may be precursors of myofibroblasts.
      This study examined the contribution of monocyte/macrophage lineage cells to
      neointimal cellular mass in a porcine model of thermal vascular injury. Thermal
      coronary artery injury caused medial smooth muscle cell necrosis and
      transformation of the media into an extracellular matrix barrier. The neointimal
      hyperplasia that developed over the injury sites was evaluated by light
      microscopy, electron microscopy and immunohistochemistry. At day 3, blood
      monocytes were adhered to the vessel wall and infiltrated the fibrotic media. At
      day 14, 42+/-3.9% of neointimal cells had a monocytic nuclear morphology and
      expressed macrophage-specific antigen SWC3 (identified by monoclonal antibody
      DH59B). Moreover, 9.2+/-1.8% of neointimal cells co-expressed SWC3 and alpha
      smooth muscle actin and had ultrastructural characteristics intermediate between
      macrophages and myofibroblasts. At day 28, 10.5+/-3.5% of cells expressed SWC3
      and 5.2+/-1.8% of cells co-expressed SWC3 and alpha-smooth muscle actin. This
      study indicates that hematopoietic cells of monocyte/macrophage lineage
      abundantly populate the neointima in the process of lesion formation and may be
      precursors of neointimal myofibroblasts after thermal vascular injury.

PMID- 12048126
TI  - Spontaneous atherosclerosis in the proximal aorta of LPA transgenic mice on a
      normal diet.
AB  - Serum levels of Lp(a) lipoprotein are under genetic control and a high level is a
      risk factor for atherosclerotic disease. We have examined the aorta of LPA
      transgenic mice and their non-transgenic litter mates who had all been given a
      regular, not lipid fortified diet. When sacrificed, the animals had an average
      age of 66 weeks. Lipid lesions were observed in the aorta of 13 out of 18 LPA
      transgenic mice and in five out of 21 non-transgenic animals. The difference is
      statistically significant. We conclude that LPA transgenic mice develop lipid
      lesions in aorta more frequently than non-transgenic animals, even on a diet with
      a low fat content. LPA transgenic mice on a normal diet could be a useful animal
      model for the study of spontaneous human atherosclerosis, its treatment and
      prevention.

PMID- 12048127
TI  - Effect of folic acid and vitamin C supplementation on folate status and
      homocysteine level: a randomised controlled trial in Italian smoker-blood donors.
AB  - BACKGROUND: This trial sought to examine the effects of high dosage of folic acid
      and vitamin C supplementation on red blood cell folate (RCF), serum folate (SF)
      and homocysteine (Hcy) levels in subjects who smoke more than 15 cigarettes per
      day. METHODS: A prospective study of 100 Italian repeat blood donors was
      undertaken to measure RCF, SF and Hcy levels before and after 45 days of vitamin
      supplementation. All subjects were randomised into four groups: [A] folic acid
      (FA) 5 mg/day, [B] vitamin C 500 mg/day, [C] FA 5 mg/day plus vitamin C 500
      mg/day [D] no supplementation. RESULTS: Before supplementation the median RCF, SF
      and Hcy levels were similar in the four groups; 32 (40%) subjects had an RCF
      level below 340 nmol/l, 15 (18.8%) had an SF level below 6.8 nmol/l and 21
      (26.3%) had an Hcy level above 16 micromol/l. After 45 days the median RCF and SF
      levels were significantly (P<0.01) increased in all supplemented subjects. The
      median Hcy level was significantly (P=0.008) reduced in subjects supplemented
      with FA and significantly (P=0.01) increased in those supplemented with vitamin C
      alone. CONCLUSION: The supplementation with 5 FA mg/day is able to increase
      significantly both RCF and SF levels and reduce Hcy level in Italian smoker-blood
      donors.

PMID- 12048128
TI  - Change in saturated fat intake is associated with progression of carotid and
      femoral intima-media thickness, and with levels of soluble intercellular adhesion
      molecule-1.
AB  - BACKGROUND: A high saturated fat (SFA) intake may stimulate progression of
      atherosclerosis, and may be positively associated with expression of adhesion
      molecules. METHODS: In moderately hypercholesterolaemic participants of a dietary
      intervention study (n=103; 55+/-10 years), we examined associations between
      reported changes in SFA intake and changes in carotid and femoral intima-media
      thickness (IMT) and soluble intercellular adhesion molecule-1 (sICAM-1) levels
      after 2 years. The carotid and femoral IMT was assessed by high-resolution B-mode
      ultrasound images. RESULTS: After 2 years, dietary intake of SFA decreased with
      1.8+/-2.6% of energy (P<0.01). In the lowest quintile of change in SFA intake (
      5.9+/-1.4% of energy), changes in carotid and femoral IMT were +0.03 mm (SEM
      0.03) and -0.09 mm (SEM 0.07), respectively, versus +0.10 mm (SEM 0.03), +0.17 mm
      (SEM 0.07) in the top quintile (+1.6+/-0.7% of energy) (P linear trend 0.07
      (carotis), 0.02 (femoralis)). Changes in sICAM-1 were -19.0 ng/nl (SEM 5.6) in
      the lowest quintile, versus +8.6 ng/ml (SEM 5.3) in the top quintile (P linear
      trend <0.001), adjusted for baseline level, SFA intake, body mass index, age,
      changes in intake of fruit, polyunsaturated fat, and dietary cholesterol.
      Adjustments for changes in established risk factors did not alter these results.
      CONCLUSIONS: Decreased SFA intake may reduce progression of atherosclerosis, as
      assessed by IMT, and is associated with reduced levels of sICAM-1 after 2 years.
      Further research using randomised placebo-controlled trials is necessary to
      exclude potential confounding variables and to confirm causality.

PMID- 12048129
TI  - Urinary albumin excretion is related to cardiovascular risk indicators, not to
      flow-mediated vasodilation, in apparently healthy subjects.
AB  - Based on studies in diabetic and hypertensive populations it has been postulated
      that early endothelial dysfunction is the mechanism responsible for the increased
      cardiovascular risk in microalbuminuric subjects. We evaluated the relation
      between microalbuminuria and endothelial dysfunction, assessed as flow-mediated
      dilation of the brachial artery, in an apparently healthy population. Within the
      framework of the PREVEND Intervention Trial non-hypertensive and non
      hypercholesterolemic subjects were recruited on the basis of reproducible
      microalbuminuria. Using high-resolution ultrasound, flow-mediated dilation and
      nitroglycerin-mediated dilation of the brachial artery was assessed to measure
      endothelium-dependent and endothelium-independent responses, respectively. For
      the current study subjects with diabetes mellitus, clinical atherosclerosis, and
      macroalbuminuria were excluded from the analyses. We studied 421 men and 233
      women (mean age (SD) 50 (12)). Increasing levels of urinary albumin excretion
      were accompanied by a significant increase in age, percentage men, systolic and
      diastolic blood pressure, body mass index, and serum triglycerides, whereas there
      was no decrease of flow-mediated vasodilation or nitroglycerin-mediated
      vasodilation. Adjusted for age and sex, urinary albumin excretion was
      significantly related to systolic (r=0.19, P<0.001) and diastolic (r=0.16,
      P<0.001) blood pressure, body mass index (r=0.18, P<0.001), and triglycerides
      (r=0.13, P=0.001), but not to flow-mediated vasodilation (r=-0.01, P=0.8). In
      contrast to blood pressure, body mass index, and triglycerides, there was no
      relation between urinary albumin excretion and flow-mediated vasodilation in
      apparently healthy subjects. These data suggest that the presence of atherogenic
      risk factors precedes the development of endothelial dysfunction in
      microalbuminuric, but otherwise healthy subjects.

PMID- 12048130
TI  - Activity and concentration of lipoprotein lipase in post-heparin plasma and the
      extent of coronary artery disease.
AB  - Numerous studies have found polymorphisms in the lipoprotein lipase (LPL) gene to
      be associated with the risk of coronary artery disease (CAD), implicating LPL in
      the development of atherothrombotic disease. It remains controversial, however,
      whether LPL acts in a pro- or anti-atherogenic fashion. We quantitated activity
      and concentration of LPL in post-heparin plasma from 194 male patients undergoing
      coronary angiography. HDL cholesterol was significantly associated with LPL
      activity quartiles (1.09+/-0.26 the highest vs. 0.96+/-0.25 mmol/l the lowest
      quartile, P<0.01). There was also a trend towards higher total (5.61+/-1.33 vs.
      5.16+/-1.44 mmol/l, P=0.059) and LDL cholesterol (3.92+/-1.39 vs. 3.46+/-1.06
      mmol/l, P=0.09) with higher LPL activity. In contrast, measures of CAD extent
      showed no differences between LPL quartiles (P>0.30 for prior myocardial
      infarction, number of diseased vessels, Gensini and extent scores). Additionally,
      there was no difference in LPL activity (CAD: n=158, 168+/-70 nmol/ml/min, no
      CAD: n=36, 180+/-89 nmol/ml/min, P=0.47) or concentration (280+/-121 ng/ml and
      288+/-111 ng/ml, P=0.72) between patients with and without CAD. Our data show
      that, in spite of an association with lipoprotein parameters, LPL in post-heparin
      plasma is unrelated to the presence or the extent of CAD. Therefore, lipoprotein
      lipase determination in plasma does not appear to be a useful marker in the
      assessment of CAD risk.

PMID- 12048131
TI  - Arterial wall thickness and the risk of recurrent ischemic events in carriers of
      the prothrombin G20210A mutation with clinical manifestations of atherosclerosis.
AB  - The G20210A mutation in the prothrombin gene is an established risk factor for
      venous thrombosis. There is controversy about the role of this mutation in
      arterial thrombotic disease and atherosclerosis. We determined the presence of
      the prothrombin mutation and examined its influence on carotid and femoral artery
      intima-media thickness (IMT) and the occurrence of new ischemic events during
      follow-up in 277 patients with clinically manifest atherosclerotic disease:
      ischemic stroke, myocardial infarction or peripheral arterial disease. The mean
      age at entry was 63 years. Mean IMT was significantly higher in carriers of the
      prothrombin mutation (1.17 (SD 0.29) mm versus 0.97 (SD 0.25) mm:
      (delta)IMT=0.20, P=0.02). The increase in IMT was not attributable to differences
      in age, type of arterial disease or cardiovascular risk factors between carriers
      and non-carriers. During a mean follow-up of 3.5 years, a strong trend for more
      ischemic events was observed: 4 of the 11 carriers suffered from a recurrent
      ischemic event, compared with 30 of the 164 male non-carriers (36 versus 18%;
      P=0.06). These results suggest that the G20210A mutation contributes to the
      process of arterial wall thickening and is associated with the occurrence of
      ischemic events in a cohort of elderly persons with established atherosclerosis.

PMID- 12048132
TI  - Size at birth and carotid atherosclerosis in later life.
AB  - Several studies have shown that low birthweight is associated with a higher risk
      of stroke and coronary heart disease in later life. Increased atherogenesis may
      be one underlying mechanism, but few studies have examined this directly. We used
      duplex ultrasonography to assess the extra-cranial carotid arteries of 389
      elderly men and women born and still living in Sheffield, UK, whose recorded
      birth measurements were available. Men and women who had weighed 6.5 lbs or less
      at birth had a higher risk of having carotid stenosis >30% than those who weighed
      over 7.5 lbs, but this trend was not statistically significant (OR 1.8, 95% CI
      1.0-3.3). Women who had been lighter or who had a smaller head circumference at
      birth tended to have an increased intima-media thickness, but these relations
      ceased to be statistically significant after adjustment for gestational age and
      cardiovascular risk factors. In men, by contrast, an increased intima-media
      thickness was associated with having been heavier at birth (P=0.049) or having
      had a larger abdominal circumference at birth (P=0.040), after adjustment for
      gestational age and cardiovascular risk factors. These results provide little
      evidence that impaired fetal growth increases susceptibility to atherogenesis.

PMID- 12048133
TI  - Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus infections and the
      risk of peripheral arterial disease in young women.
AB  - Sero-epidemiological case control studies have observed positive relations
      between infections with Chlamydia pneumoniae, Helicobacter pylori or
      cytomegalovirus (CMV) and the occurrence of coronary artery disease (CAD) and
      stroke. Moreover, positive relations between 'infection burden' and CAD and the
      role of inflammation have recently been described. However, the relations between
      infection, inflammation and the occurrence of peripheral arterial disease (PAD)
      have not been reported so far. We performed a multi-centre population-based case
      control study, using serum samples of 228 young female PAD patients and 643
      control women to determine IgG antibody titres and C-reactive protein. The odds
      ratios for PAD in women with serological evidence for infection with C.
      pneumoniae, H. pylori or CMV were 2.0 (95% CI; 1.3-3.1), 1.6 (95% CI; 1.1-2.2)
      and 1.6 (95% CI; 1.1-2.3), respectively. The cumulative number of infections was
      positively related to the risk of PAD; the odds ratio was 1.5 (95% CI; 1.0-2.4),
      2.7 (95% CI; 1.6-4.4) and 3.5 (95% CI; 1.5-8.1) for women with one, two or three
      infections, respectively. This increased risk, related to the 'infection burden',
      was found again in the subgroup of women with a high CRP level, but not in the
      subgroup with a low CRP level. Infections might be a causal component in the
      development of PAD. The risk of PAD is not only related to a single pathogen in
      particular, but also to the cumulative number of infections. The positive
      relation between 'infection burden' and PAD was only found in women with a high
      CRP level, which indicates that inflammation might be involved in the process
      that leads to PAD.

PMID- 12048134
TI  - Long-term treatment with pitavastatin (NK-104), a new HMG-CoA reductase
      inhibitor, of patients with heterozygous familial hypercholesterolemia.
AB  - The clinical efficacy and safety of pitavastatin (NK-104), a novel HMG-CoA
      reductase inhibitor, during long-term treatment, were examined in 25 patients
      (male/female=11/14, mean age=53+/-13 (mean+/-SD) years) with heterozygous
      familial hypercholesterolemia (FH). After a period on placebo of >4 weeks, 2
      mg/day of pitavastatin was administered for 8 weeks, and the dose was increased
      to 4 mg/day for up to 104 weeks. Total cholesterol (TC) decreased by 31% from the
      initial value of 340+/-57 to 237+/-40 mg/dl (P<0.0001) at week 8. During
      treatment with the higher dose, TC decreased even further to 212+/-35 mg/dl at
      week 12; it decreased by 37% from the initial value (P<0.0001). Similarly, the
      baseline low-density lipoprotein (LDL)-cholesterol (LDL-C) decreased by 41% at
      week 8, and by 49% at week 12, from 267+/-61 mg/dl at baseline. These findings
      indicate a dose-dependent effect of the drug on TC and LDL-C concentrations. To
      examine whether the levels of circulating matrix metalloproteinases (MMPs) and
      their endogenous inhibitors (tissue inhibitors of metalloproteinases: TIMPs) are
      altered during lipid-lowering therapy, we also measured their plasma levels. The
      mean levels of MMP-2 and -3 were significantly increased. No significant
      alteration was found in MMP-9, TIMP-1 and -2 levels. As for the safety of
      pitavastatin, adverse reactions were observed in one case (4%) of subjective and
      objective symptoms. The effects of pitavastatin on TC and LDL-C were stable
      during long treatment of patients with heterozygous FH.

PMID- 12048135
TI  - Chlamydia pneumoniae infection is not involved in carotid artery stenosis.
AB  - Recent studies have suggested the existence of a close relationship between
      Chlamydia pneumoniae infection and atherosclerosis. However, it has been
      speculated that C. pneumoniae infection is not associated with early
      atherosclerosis but with advanced atherosclerosis. In the present study, we test
      this hypothesis. In 524 consecutive patients who underwent cerebral angiography
      were recruited for the study. From the films obtained during angiography, percent
      stenosis of neck internal carotid artery was calculated according to the method
      of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Serum C.
      pneumoniae IgG and IgA antibodies were measured by a commercial ELISA enzyme
      immunoassay kit. Cerebrovascular risk factors such as age, gender, hypertension,
      diabetes mellitus, hyperlipidemis and smoking were assessed by interview. Old age
      above 60 years and diabetes mellitus were found to be independent risk factors
      for carotid artery stenosis in this study after adjustment for cerebrovascular
      risk factors. When we defined carotid artery stenosis as the presence of greater
      than 30% stenosis of one artery, there was no association after adjustment for
      other risk factors between C. pneumoniae IgG and IgA seropositivity and the
      presence of carotid artery stenosis for any cut-off value of seropositivity. When
      we defined carotid artery stenosis as the presence of greater than 70%, there was
      also no association between C. pneumoniae IgG and IgA seropositivity and the
      presence of carotid artery stenosis for any cut-off value of seropositivity.
      These results suggest that C. pneumoniae infection is not associated with carotid
      artery atherosclerosis.

PMID- 12048136
TI  - The frequency of the cholesteryl ester transfer protein-TaqI B2 allele is lower
      in African Americans than in Caucasians.
AB  - Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl
      ester for triglyceride between high density lipoprotein (HDL) and very low
      density lipoprotein. The B2 allele of the TaqIB polymorphism located in the first
      intron of the CETP gene occurs with an allele frequency of about 0.40 in
      Caucasians and is associated with decreased CETP levels and activity and with
      higher HDL-cholesterol (HDL-C) levels in this racial group. We hypothesized that
      the higher levels of HDL-C seen in African Americans compared with Caucasians
      could be in part explained by a higher frequency of the TaqI B2 allele. We
      determined the distribution of this polymorphism in a total of 395 African
      Americans and 362 Caucasian ascertained as two independent cohorts: one of
      healthy volunteers (NORM) and the other of patients undergoing cardiac
      catheterization (CATH). Of the 244 NORM-African Americans studied, 56% were B1B1,
      37% B1B2 and 7% B2B2, compared with the 224 NORM-Caucasians of which 33% were
      B1B1, 45% B1B2 and 22% B2B2. In the CATH-African American group (n=151) 51% were
      B1B1, 41% B1B2 and 8% B2B2 compared with 35% CATH-Caucasians B1B1, 54% B1B2 and
      11% B2B2. The frequency of the B2 allele in the Caucasian subjects in both
      cohorts was similar to that reported in the literature. The frequency of the B2
      allele was significantly lower in African Americans than in Caucasians in the
      NORM group (0.26 vs 0.44; chi(2)=36.5, P<0.001) and in the CATH group (0.28 vs
      0.38, chi(2)=4.7, P=0.01). Carriers of the B2 allele had higher HDL-C levels
      compared with B1B1 subjects in Caucasians (NORM: 57 vs 53 mg/dl, P=0.035; CATH:
      47 vs 42 mg/dl, P=0.049) and in CATH-African Americans (48 vs 43 mg/dl, P=0.028),
      but not in NORM-African Americans (55 vs 54 mg/dl, P=0.494). There were no other
      significant associations between this polymorphism and other lipids and
      lipoproteins in the subjects studied. These results suggest that, in contrast to
      our hypothesis, the B2 allele of the TaqIB polymorphism is less frequent in
      African Americans compared with Caucasians and that this polymorphism is unlikely
      to contribute to the higher levels of HDL-C reported in the African American
      population.

PMID- 12048137
TI  - Leukocyte count and vascular function in Type 2 diabetic subjects with treated
      hypertension.
AB  - BACKGROUND: Traditional cardiovascular risk factors may only partially explain
      abnormal vascular function in Type 2 diabetic patients. This study examined the
      associations between vascular function and markers of inflammation in Type 2
      diabetic subjects with treated hypertension. METHODS: Flow-mediated dilatation
      (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) of the brachial artery
      were used to assess endothelium-dependent and -independent function,
      respectively, in 29 hypertensive Type 2 diabetic subjects (HbA1c <9%), and 17
      healthy control subjects. Plasma C-reactive protein (CRP), fibrinogen,
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and leukocyte
      count were used as markers of inflammation. Soluble L-selectin, P-selectin, and
      von Willebrand factor (vWf) were measured to assess leukocyte, platelet and
      endothelial cell activation, respectively. RESULTS: Compared with controls,
      diabetic subjects had impaired FMD (3.9+/-3.0 vs. 5.5+/-2.4%, P=0.07) and GTNMD
      (11.4+/-4.8% vs. 15.4+/-7.1%, P=0.04). They also had higher levels of CRP (2.7+/
      2.6 vs. 1.4+/-1.1 mg/l, P=0.03), fibrinogen (3.4+/-0.7 vs. 2.7+/-0.3 g/l,
      P<0.001) and TNF-alpha (20.9+/-13.4 vs. 2.5+/-1.7 pg/l, P<0.001). In diabetic
      subjects, after adjustment for age and gender, leukocyte count was an independent
      predictor of FMD (P=0.02), accounting for 17% of total variance. Similarly,
      leukocyte count (P<0.001) accounted for 23% and IL-6 (P=0.03) for 12% of the
      variance in GTNMD. vWf was correlated with leukocyte count (r=0.38, P=0.04), FMD
      (r=-0.35, P=0.06) and GTNMD (r=-0.47, P=0.009), whilst P-selectin correlated with
      fibrinogen (r=0.58, P=0.001). CONCLUSION: These cross-sectional observations are
      consistent with the hypothesis that reduced FMD and GTNMD in Type 2 diabetes is
      at least in part secondary to increased inflammation, with associated endothelial
      and platelet activation.

PMID- 12048138
TI  - Genetic determinants of the response to bezafibrate treatment in the lower
      extremity arterial disease event reduction (LEADER) trial.
AB  - Genetic determinants of baseline levels and the fall in plasma triglyceride and
      fibrinogen levels in response to bezafibrate treatment were examined in 853 men
      taking part in the lower extremity arterial disease event reduction (LEADER)
      trial. Three polymorphisms in the peroxisome proliferator activated receptor
      alpha (PPARalpha) gene were investigated (L162V, G>A in intron 2 and G>C in
      intron 7), two in the apolipoprotein CIII (APOC3) gene (-482C>T and -455T>C) and
      one in the beta-fibrinogen (FIBB) gene (-455G>A). The presence of diabetes
      (n=158) was associated with 15% higher triglyceride levels at baseline compared
      to non-diabetics (n=654) (P<0.05). Among the diabetic group, carriers of the
      PPARalpha intron 7 C allele had 20% lower triglyceride levels compared to
      homozygotes for the common G allele (P<0.05), with a similar (non-significant)
      trend for the L162V polymorphism, which is in linkage disequilibrium with the
      intron 7 polymorphism. For the APOC3 gene, carriers of the -482T allele had 13%
      lower baseline triglyceride levels compared to -482C homozygotes (P<0.02), but no
      effect was observed with the -455T>C substitution. In the non-diabetic patients,
      the PPARalpha V162 allele was significantly associated with 9% higher baseline
      triglyceride levels (P<0.03) and a similar, but non-significant trend was seen
      for the intron 7 polymorphism. Overall, triglyceride levels fell by 26% with 3
      months of bezafibrate treatment, and current smokers showed a poorer response
      compared to ex/non-smokers (23% fall compared to 28% P=0.03), but none of the
      genotypes examined had a significant influence on the magnitude of response.
      Carriers of the -455A polymorphism of the FIBB gene had, as expected, marginally
      higher baseline fibrinogen levels, 3.43 versus 3.36 g/l (P=0.055), but this
      polymorphism did not affect response to treatment. Overall, fibrinogen levels
      fell by 12%, with patients with the highest baseline fibrinogen levels showing
      the greatest decrease in response to bezafibrate. For both the intron 2 and the
      L162V polymorphisms of the PPARalpha gene there was a significant interaction
      (both P<0.01) between genotype and baseline levels of fibrinogen on the response
      of fibrinogen levels to bezafibrate, such that individuals carrying the rare
      alleles in the lowest tertile showed essentially no overall decrease compared to
      a 0.18 g/l fall in homozygotes for the common allele. Thus while these genotypes
      are a minor determinant of baseline triglyceride and fibrinogen levels, there is
      little evidence from this study that the magnitude of response to bezafibrate
      treatment in men with peripheral vascular disease is determined by variation at
      these loci.

PMID- 12048139
TI  - Family history of cardiovascular events and endothelial dysfunction in children
      with familial hypercholesterolemia.
AB  - OBJECTIVES: in patients with familial hypercholesterolemia (FH), the propensity
      towards atherosclerosis may vary considerably. In the general population, a
      positive family history is associated with an increased risk for cardiovascular
      events. Since endothelial dysfunction is predictive for future cardiovascular
      events, we evaluated whether FH-children with a positive family history of
      premature cardiovascular disease have more pronounced endothelial dysfunction
      compared to children with a negative family history. STUDY DESIGN: 50 FH
      children, 10-18 years, participated in this study. Thirty-one children had a
      positive family history for cardiovascular events (fh(+)) and 19 children had no
      events in the family (fh(-)). Nineteen matched siblings participated as controls.
      Endothelial function was assessed by testing the flow mediated dilatation (FMD)
      of the brachial artery. RESULTS: baseline characteristics were comparable for
      fh(+), fh(-) and controls. Lipid levels were significantly higher in FH children.
      In FH, FMD was impaired compared to controls (11.7+/-4.4 vs. 15.6+/-6.8%,
      P<0.03). In addition, FMD was significantly lower in fh(+) compared to fh(-)
      (10.7+/-9.9 vs. 13.3+/-4.6%, P<0.05). CONCLUSION: In FH-children, endothelial
      function is impaired compared to matched controls. This impairment is most
      pronounced in FH children with a positive family history of premature
      cardiovascular disease.

PMID- 12048141
TI  - On the coronary heart disease mortality in Turkey.

PMID- 12048140
TI  - The macrophage hemoglobin scavenger receptor (CD163) as a genetically determined
      disease modifying pathway in atherosclerosis.

PMID- 12048142
TI  - Long-term treatment with atorvastatin in adolescent males with heterozygous
      familial hypercholesterolemia.

PMID- 12048144
TI  - Heterogeneity in functional status among older outpatients with schizophrenia:
      employment history, living situation, and driving.
AB  - Schizophrenia and aging are both risk factors for deficits in independent
      functioning, yet relatively few studies have examined the level and predictors of
      functional status of older outpatients with schizophrenia. We compared employment
      history, current living situation, and driving status of 83 middle-aged and
      elderly outpatients with schizophrenia (mean age 59 years), and 46
      demographically equivalent normal comparison subjects. We also examined the
      relationships of neuropsychological functioning and psychiatric symptoms to these
      aspects of everyday functioning. The schizophrenia patient group had consistently
      worse functional status than the normal comparison group, but 30% of the patients
      were employed at least 50% of the time during their post-schizophrenia-onset
      adult lives, 73% were living in a house or apartment and responsible for meeting
      most of their own daily needs, and 43% were current drivers. Severity of negative
      symptoms (but not that of positive symptoms) was inversely correlated with
      functional status. Worse performance on a neuropsychological battery was
      generally associated with worse functional status. These findings counter notions
      that functional impairment is inevitable in older schizophrenia patients, and
      highlight the importance of assessment of functional skills and possibly
      targeting them as a treatment focus.

PMID- 12048145
TI  - Neuropsychological functioning in elderly patients with schizophrenia and
      Alzheimer's disease.
AB  - Cognitive functioning was compared in elderly patients with schizophrenia,
      elderly patients with probable Alzheimer's disease (AD), and matched healthy
      controls using a brief neuropsychological battery. Both schizophrenia and AD
      patients demonstrated marked impairment as compared to controls, with the profile
      of neuropsychological deficits in both disorders appearing remarkably similar.
      Only visual confrontation naming, verbal delayed recall, and rate of forgetting
      (i.e. savings score) significantly differentiated between the two patient groups,
      with AD patients showing poorer overall recall and more rapid forgetting of
      verbal information over delay. In addition, schizophrenia subjects showed a
      significantly greater deficit in visual confrontation naming than the AD group.
      The relationship of neuropsychological function and clinical symptoms of
      schizophrenia subjects was also examined. Results showed that word list learning,
      delayed recall, and rate of forgetting correlated most strongly with positive and
      negative symptoms. Recent neuropathological studies have indicated abnormalities
      in specific subfields of the hippocampal formation in schizophrenia that are also
      severely affected in AD. Though the specific histopathology of the two disorders
      differs, abnormalities in the common sites may underlie the common
      neuropsychological profile.

PMID- 12048146
TI  - Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms
      and neurocognitive rate-limiters for the development of social behavior skills.
AB  - Neurocognitive deficits are believed to be important predictors of functional
      outcome in chronic psychotic disorders, but few supporting studies have utilized
      prospective designs and adequate control. The aim of this study was to estimate
      the relative influence of symptoms and neurocognitive deficits on the development
      of social behavior skills in a cohort of individuals with schizophrenia or
      schizoaffective disorder recovering from acute symptom exacerbations. Forty-six
      individuals were recruited upon discharge from an inpatient unit and completed
      assessments of symptoms, neurocognitive function, and social behavior at 3-month
      intervals for 1 year. Correlational analyses and random regression models were
      used to model social behavioral capacities longitudinally. Social behavior
      improved modestly (10% improvements in ratings) over the follow-up period for the
      group as a whole. Disorganized and negative symptoms, as well as neurocognitive
      deficits in short-term and working memory predicted changes in social behavior
      over time. Individuals with better working memory function showed significantly
      greater abilities to recover social behavior skills, whereas those with working
      memory deficits showed no functional improvement over time. Both symptoms and
      neurocognitive deficits are important determinants of functional outcome in
      schizophrenia. It is proposed that clinicians should consider neurocognitive
      thresholds for treatment response when developing rehabilitation plans.

PMID- 12048147
TI  - Personality dimensions and neuropsychological performance in first-degree
      relatives of patients with schizophrenia and affective psychosis.
AB  - Several studies have found a significant increase in the prevalence of some
      personality disorders in the first-degree relatives of patients with
      schizophrenia; other studies have found subtle neuropsychological deficits in
      these relatives. However, little is known about the specificity of the
      personality traits reported or about the relationship between these traits and
      the neuropsychological deficits.One-hundred first-degree relatives of patients
      with schizophrenia (SR) and 88 first-degree relatives of affective psychotic
      patients (APR) completed the Eysenck Personality Questionnaire which measures
      extraversion, neuroticism, and psychoticism; they were also administered the
      National Adult Reading Test (NART), the Trail Making Test (TMT) and a Verbal
      Fluency Test (VFT). The male relatives of patients with schizophrenia scored
      significantly higher on the psychoticism scale than the male relatives of
      affective psychotic patients. In the SR group, there were significant
      correlations between the TMT performance and the extraversion scores and, between
      the IQ scores and the psychoticism scores. However, when logistical regression
      analyses were performed, none of the three personality scores predicted any of
      the neuropsychological performance in either the SR or the APR group. These
      results indicate some specificity as well as sex differences in the psychoticism
      dimension. Moreover, the relationship between the personality dimensions and the
      neuropsychological performance could indicate that psychoticism increases
      vulnerability to psychosis whereas extraversion decreases it.

PMID- 12048148
TI  - Decision making deficits in patients with first-episode and chronic
      schizophrenia.
AB  - A considerable body of evidence suggests that the dorsolateral prefrontal cortex
      is dysfunctional in schizophrenia. However, relatively few studies have explored
      the involvement of other areas of the frontal cortex. Research suggests that the
      orbitofrontal cortex (OFC) plays an important role in decision making processes.
      We assessed the decision making cognition of first-episode and chronic
      schizophrenic patients with a novel task sensitive to orbitofrontal dysfunction.
      Both first-episode and chronic patients with schizophrenia took longer than
      matched controls to make decisions, and both groups were also impaired on a
      measure of risk adjustment. The impairment in these measures was more severe in
      the chronic patients than in the first-episode patients, and only the chronic
      patients made significantly fewer optimal decisions than controls. These results
      contribute to increasing evidence of orbitofrontal dysfunction in schizophrenia,
      and suggest that disease progression or the effects of long term antipsychotic
      medication may influence performance on this task.

PMID- 12048149
TI  - The relationship between cognitive dysfunction and coping abilities in
      schizophrenia.
AB  - Cognitive dysfunction is a core feature of schizophrenia [Psychiatr. Clin. North
      Am., 16 (1993) 295; Psychopharmacology: The fourth generation of progress, Raven
      Press, New York (1995) 1171; Clinical Neuropsychology, Oxford University Press,
      New York (1993) 449] and is related to psychosocial functioning in this
      population [Am. J. Psychiatry, 153 (1996) 321]. It is unclear whether cognitive
      dysfunction is related to specific areas of functioning in schizophrenia, such as
      coping abilities. Individuals with schizophrenia have deficient coping skills,
      which may contribute to their difficulties dealing with stressors [Am. J.
      Orthopsychiatry, 62 (1992) 117; J. Abnorm. Psychol., 82 (1986) 189]. The current
      study examined the relationship between coping abilities and cognitive
      dysfunction in a community sample of individuals with schizophrenia. It was
      hypothesized that executive dysfunction and mnemonic impairments would be
      positively related to deficiencies in active coping efforts involving problem
      solving and self-initiation (e.g. advocating for oneself and others with mental
      illness and becoming involved in meaningful activities, such as work),
      independent of the contributions of the general intellectual deficits associated
      with the disorder and psychiatric symptoms. The results indicated that both
      executive dysfunction and mnemonic impairments were related to decreased usage of
      active coping mechanisms after controlling for general intellectual deficits.
      Further, recognition memory made independent contributions to the prediction of
      coping involving action and help seeking after controlling for the effects of
      negative symptoms. These findings suggest that individuals with schizophrenia may
      be less flexible in their use of coping strategies, which may in turn contribute
      to their difficulties in coping with mental illness and its consequences.

PMID- 12048150
TI  - The effects of stereotype suppression on psychiatric stigma.
AB  - The effects of stereotype suppression on psychiatric stigma were investigated in
      two studies. In experiment 1, 52 participants were presented with a photograph of
      someone labeled with schizophrenia and instructed to write a passage describing a
      day in that person's life. Half of the participants were instructed to avoid
      using schizophrenia-related stereotypes in their passages (the stereotype
      suppression condition). Participants were then presented with a photograph of a
      different individual labeled with schizophrenia and asked to write another
      passage with stereotype suppression instructions omitted. The results showed that
      while stereotype suppression occurred for the first passage, the expected rebound
      effects were not observed in the second passage. Furthermore, the results were
      unchanged when participants' prior experience with persons with mental illness
      was considered. In a second study, the effects of stereotype suppression on
      behavior (i.e. seating distance from a person with schizophrenia) were examined
      in 58 participants. While the stereotype suppression instructions resulted in
      less stereotypical passages, replicating the results of study 1, no rebound
      effects on behavior were observed. A non-significant trend was observed whereby
      previous contact with persons with mental illness was associated with less social
      distance from someone with schizophrenia. Implications of the findings for
      reducing psychiatric stigma are discussed.

PMID- 12048151
TI  - Changes in body mass index for individuals with and without schizophrenia, 1987
      1996.
AB  - The advent of the novel or atypical antipsychotic drugs has improved the
      treatment and quality of life for many individuals. However, many of these newer
      agents confer a degree of weight gain that is both greater than conventional
      antipsychotics and of a clinically meaningful magnitude. To better place this
      issue into perspective, we evaluated body mass index (BMI; kg/m2) levels and the
      prevalence of overweight and obesity among schizophrenic versus non-schizophrenic
      individuals among nationally representative samples of the US adult population
      and evaluated whether there were changes in these rates during the decade from
      1987 to 1996, a period in which use of novel/atypical agents increased. Results
      showed that mean BMI for individuals with schizophrenia is significantly higher
      than individuals who are not schizophrenic. The non-schizophrenic population
      shows steady and significant gains in BMI from 1987 to 1996 both as a whole and
      when stratified by gender and age. In contrast, time trends among the population
      of schizophrenic individuals show a more complex pattern. Specifically, for most
      groups, there is little evidence of a general trend in BMI over time. However,
      among females with schizophrenia ages 18-30, BMI has increased dramatically and
      significantly causing a much higher obesity rate among young women with
      schizophrenia in recent years relative to their non-schizophrenic counterparts.
      The mechanism that underlies this weight age and sex specific time trend is
      unclear.

PMID- 12048152
TI  - Gender differences in premorbid adjustment of patients with first episode
      psychosis.
AB  - Gender differences in premorbid adjustment, clinical presentation, and
      longitudinal course have been considered increasingly in explanatory models of
      psychotic disorders, such as the schizophrenias. Indeed, findings of a male
      propensity to poor premorbid adjustment, negative and non-affective symptoms, and
      poor outcome relative to their female counterparts, has led to suggestions that
      males are more prone to an early-onset dementia praecox type of schizophrenic
      disorder. The current study investigated a sample of 38 male and 20 female
      patients presenting with their first episode of psychosis (broadly defined, but
      excluding obvious drug-induced disorders) from a defined catchment area
      population, which had been systematically ascertained without prejudice to
      diagnostic subtype or illness duration. The study investigated gender, diagnosis
      and interaction of gender and diagnosis on differences within the three
      developmental age categories of childhood, early adolescence and late
      adolescence, to identify where, within these age categories, differences lie. The
      second part of the study was to investigate the relationship between premorbid
      adjustment, gender, and psychopathology as measured by the PANSS and SCL-90.
      General linear modelling revealed that males were reported to have had poorer
      premorbid adjustment in late adolescence when compared to females, notably in
      items examining school performance, adaptation to school, social interests and
      sociosexual development. Males were observed to have higher levels of negative
      symptoms but not for positive or general symptoms on the PANSS. This finding is
      independent from the effect of diagnosis or of the interaction effect between
      gender and diagnosis on premorbid adjustment. There were no gender effects for
      the self reported global indices on the SCL-90. The results suggest that in
      comparison with their female counterparts, males who develop a psychotic illness
      have significantly poorer premorbid adjustment at the late adolescent stage and
      that this may contribute to higher levels of negative symptoms.

PMID- 12048153
TI  - Cerebral signs of altered adaptability in females with acute psychosis.
AB  - In psychosis, behavior is not guided by sensory cues from surroundings. Novel,
      meaningful behaviors require intact integrative functions such as short-term
      memory and motor planning, as well as an optimized level of arousal. In this
      study, we monitored markers of automatic auditory processing in 15 female never
      medicated psychotic patients. Fifty-eight channels of EEG were recorded
      simultaneously with sympathetic skin responses while arousing auditory stimuli
      were delivered. Neuropsychological tests concentrating on frontal lobe functions
      were also performed. Prominent neurophysiological and behavioral signs of
      increased cortical activation were observed in psychotic patients. This
      widespread disinhibition may attempt to compensate for the impairment of neuronal
      processing of sensory input from surroundings in the earliest stages of a
      psychotic illness.

PMID- 12048154
TI  - Sinistrality in schizophrenia.
AB  - Sinistrality characterized by an excess of non-right handedness has been reported
      in schizophrenic patients. Two factors, sex and kind of evaluation of handedness
      have contributed to major discrepancies across studies. AIM: The hypothesis
      tested was that schizophrenic patients show a sinistral shift in handedness
      compared to controls taking into account the sex and using a continuum scoring
      system for evaluating handedness. METHODS: Seventy-three (73.1% males)
      schizophrenic patients (DSMIV) and 81 (64.2% males) controls were evaluated with
      the Edinburgh Handedness Inventory (EHI [Neuropsychologia, 9 (1971) 97]).
      RESULTS: The EHI score mean difference between patients with schizophrenia and
      control group was not significant when sex was taken into account. CONCLUSION:
      Schizophrenic patients taken as a whole did not show a sinistral shift in
      handedness even if the sex and the continuum score for handedness were
      considered.

PMID- 12048155
TI  - Aminopeptidase inhibitors bestatin and actinonin inhibit cell proliferation of
      myeloma cells predominantly by intracellular interactions.
AB  - The antiproliferative effects of bestatin and actinonin on U937 and K562 cells
      have been compared with their inhibitory activity on cell surface
      aminopeptidases. The results strongly suggest that the inhibition of cell surface
      aminopeptidases cannot be the main reason for the inhibition of cell
      proliferation. This was confirmed by studying the effect of buthionine
      sulfoximine (BSO), MK-571 (3-([[3-(2-[7-chloro-2-quinolinyl]-ethenyl)-phenyl]-[(3
      dimethyl-amino-3-oxopropyl)-thio]-methyl]thio)propanoic acid) and verapamil on
      the inhibition of cell proliferation by bestatin and actinonin. BSO and MK-571,
      which inhibit the efflux of drugs mediated by multidrug resistance-associated
      protein (MRP), increased the action of both inhibitors, indicating that the
      latter enter the cells and that their export is mediated by MRP in both cell
      lines. Verapamil significantly increased the inhibitory activity of bestatin on
      K562 cells, indicating that the intracellular concentration of bestatin can be
      mediated also by P-glycoprotein.

PMID- 12048156
TI  - Inducible nitric oxide synthase expression of tumor and stromal cells is
      associated with the progression of 7,12-dimethylbenz[a]anthracene-induced rat
      mammary tumors.
AB  - The purpose of this study was to investigate the alteration of inducible nitric
      oxide synthase (iNOS) expression in rodent mammary tumors. We examined iNOS
      expression by immunohistochemistry and Western blot analysis in 7,12
      dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumors. In Western blot
      analysis, invasive carcinomas showed strong expression of iNOS; however,
      carcinomas in situ, atypical tumors and normal mammary tissue revealed
      insignificant expression. In immunohistochemistry, tumors revealed positive
      immunoreactivity in either tumor epithelial, stromal or endothelial cells. In
      particular, invasive carcinomas showed strong expression at the tumor cells
      bordering on glandular lumen containing necrotic or apoptotic nuclear debris.
      Invasive carcinomas showed higher positive immunoreactivity of iNOS compared with
      normal mammary tissue, atypical tumors, and carcinomas in situ. Stromal iNOS
      expression was correlated with apoptotic count. These results suggest that iNOS
      expression of tumor and stromal cells is associated with the progression of DMBA
      induced rat mammary tumors.

PMID- 12048158
TI  - Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis.
AB  - In continuation of our works of natural and synthetic products as cancer
      chemopreventive agents, we have examined emodin and cassiamin B, which were
      isolated from Cassia siamea. These compounds exhibited the remarkable anti-tumor
      promoting effect on two-stage carcinogenesis test of mouse skin tumors induced by
      7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13
      acetate (TPA) as a promoter by both topical application. Furthermore, emodin
      exhibited potent inhibitory activity on two-stage carcinogenesis test of mouse
      skin tumors induced by nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]
      5-nitro-6-methoxy-3-hexeneamide as an initiator and TPA as a promoter.

PMID- 12048157
TI  - Effects of N-methyl-N'-nitro-N-nitrosoguanidine on the human colorectal polyps
      consecutively maintained in SCID mice.
AB  - N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatments for a long period induced
      morphological and molecular alterations in the benign human colorectal polyps
      which were maintained in the severe combined immunodeficient C.B17/N-scid/scid
      mice. Thirty four xenografts of colorectal polyps from five solitary polyp and
      three familial polyposis patients were examined for K-ras and p53 mutations. Six
      K-ras mutations were induced in 16 grafts treated with MNNG more than five times,
      while no K-ras mutations were detected in 14 untreated grafts (P<0.05).
      Additional and new K-ras mutations were also induced in two polyps in which K-ras
      mutation had pre-existed. p53 mutations were not observed in both MNNG-treated
      and untreated groups. The mutations in K-ras gene were induced at codon 12 (GGT-
      >GAT) except one at codon 13 (GGC-->GGT). The results indicate that K-ras
      mutation plays an important role in human colorectal carcinogenesis as is the
      case in experimental animals.

PMID- 12048159
TI  - FCLA chemiluminescence from sonodynamic action in vitro and in vivo.
AB  - In this work, the chemiluminescence method was engaged for the first time to
      detect the active oxygen species during sonodynamic action in vitro and in vivo.
      We used FCLA (3,7-dihydro-6-[4-[2-[N'-(5-fluoresceinyl)thioureido]-ethoxy]phenyl]
      2-methylimidazo[1,2-a]pyrazin-3-one sodium salt), which can selectively react
      with singlet oxygen ((1)O(2)) or superoxide anion (O(2)(-)) to emit photons, to
      detect in real time oxygen free radical formation in the sonosensitization of
      hematoporphyrin derivative. The results show that (1)O(2) is involved in the
      sonosensitization. In in vivo experiments, a tumor-imaging method by sonodynamic
      chemiluminescence detection was established. This method could have potential
      applications in clinics for tumor diagnosis.

PMID- 12048160
TI  - Growth suppression and immunogenicity enhancement of Hep-2 or primary laryngeal
      cancer cells by adenovirus-mediated co-transfer of human wild-type p53,
      granulocyte-macrophage colony-stimulating factor and B7-1 genes.
AB  - Co-transfer of immunomodulatory and antiproliferative genes may be the basis for
      new strategies to potentiate tumor regression. In this study, we evaluated the in
      vitro effect of the introduction of human wild-type p53, granulocyte-macrophage
      colony-stimulating factor (GM-CSF), and B7-1 genes via recombinant adenovirus on
      the growth and immunogenicity of Hep-2 or primary laryngeal cancer cells. By the
      introduction of wild-type p53 gene, the growth of Hep-2 cells was inhibited via
      enhanced apoptosis. By the introduction of GM-CSF and B7-1 genes, the
      immunogenicity of cancer cells was enhanced. Significant proliferation of tumor
      infiltrating lymphocytes (TILs) and tumor-specific cytotoxicity of cytotoxic T
      lymphocytes (CTLs) were induced in vitro. Furthermore, the combinative effect of
      GM-CSF and B7-1 was even more evident than that of any one of them singly. These
      results suggest that the co-transfer of human wild-type p53, GM-CSF and B7-1
      genes into tumor cells via recombinant adenovirus may be further developed into a
      potential combination gene therapy strategy for cancer.

PMID- 12048161
TI  - Antitumor activity of the sporoderm-broken germinating spores of Ganoderma
      lucidum.
AB  - The inhibitory effects of the dormant spores, the germinating spores, the
      sporoderm-broken germinating spores (SBGS), and the lipids extracted from the
      germinating spores of Ganoderma lucidum on the growth of mouse hepatoma, sarcoma
      S-180, and reticulocyte sarcoma L-II cells were investigated, respectively. The
      dormant spores could be activated by germination, and thus the bioactivities of
      the spores might be enhanced. The sporoderm-broken spores could show much higher
      bioactivities than the whole spores. Both the lipids extracted from the
      germinating spores and the SBGS of G. lucidum had remarkable antitumor effects in
      a dose-dependent manner, and could significantly inhibit three tumors with an
      inhibition of 80-90%.

PMID- 12048162
TI  - Combination effects of alkylphosphocholines and gemcitabine in malignant and
      normal hematopoietic cells.
AB  - Cytosine arabinoside (ara-C) and 2',2'-difluorodeoxycytidine (Gem) were compared
      in leukemia cells, with Gem being more potent than ara-C. Gem was combined with
      hexadecylphosphocholine (HPC) or erucylphospho-N,N,N-trimethylpropanolamine
      (ErPC(3)) in resistant CML cells. Supra-additive effects were seen in K-562 cells
      after concomitant and sequential exposure of Gem followed by HPC. The reverse
      sequence resulted in antagonism. Both effects were more significant when HPC was
      exchanged for ErPC(3). Gem or HPC failed to induce DNA laddering in K-562 cells,
      but apoptotic signals were transferred by the Gem-exposed SKW-3 cytosolic
      fraction to K-562 nuclei. HPC did not increase the clastogenicity of Gem and
      counteracted its mitotic inhibition in murine bone marrow. Thus, the combination
      of Gem and an alkylphosphocholine is advantageous in terms of their complementary
      mode of action, resulting in increased cytotoxicity and lowered myelotoxicity.

PMID- 12048163
TI  - Expression of cytosolic and group X secretory phospholipase A(2) genes in human
      colorectal adenocarcinomas.
AB  - Gene expression of cytosolic phospholipase A(2) (cPLA(2)) and protein level of
      secretory PLA(2) group X (sPLA(2)-X) are upregulated in human colorectal cancer
      and provide cyclooxygenase-2 (COX-2) with arachidonic acid, resulting in
      increased levels of PGE(2). Mutated ras-genes are suggested to be involved in the
      regulatory pathway of cPLA(2) in lung cancer cells. We analysed the gene
      expression of cPLA(2) and sPLA(2)-X in 42 and 38 primary colorectal tumours,
      respectively, with and without K-ras mutations. We found an up-regulation of
      cPLA(2) mRNA but the induction in tumour tissues does not correlate with Ras-gene
      mutations. Moreover, our results cannot consistently reflect an overexpression of
      sPLA(2)-X gene in colorectal cancer tissues.

PMID- 12048164
TI  - Failure to activate caspase 3 in phorbol ester-resistant leukemia cells is
      associated with resistance to apoptotic cell death.
AB  - The protein kinase C (PKC)-specific inhibitor, Ro-31-8220, has been shown to
      induce anti-proliferation and apoptosis of human cancer cell lines. In the
      present study, we determined the molecular pathways that lead to apoptosis after
      treatment of cells with the PKC-specific inhibitor RO-31-8220. For this, we used
      the U937 human leukemia cell line and a phorbolmyristate acetate (PMA)-resistant
      derivative cell line, R-U937. Ro-31-8220 treatment of U937 cells leads to
      apoptosis, which is accompanied by activation of caspase 3 (as measured by
      decreased levels of the 32kDa inactive form and increased proteolytic cleavage of
      phospholipase C (PLC)-gamma1). The broad-range caspase inhibitor z-VAD-fmk
      inhibits this induction of apoptosis, supporting a direct link between caspase
      activation and Ro-31-8220 induction of apoptosis. This activation of apoptosis is
      also accompanied by release of cytochrome c, but not by altered expression of Bcl
      2 family protein or IAP family proteins. In R-U937 cells, Ro-31-8220 fails to
      cause release of cytochrome c, activation of caspase 3, or apoptosis. Activation
      of Akt occurs to a greater extent in the R-U937 cells than the U937 cells and
      thus might be related to protection from Ro-31-8220-induced apoptosis.

PMID- 12048165
TI  - Assessment of chromosomal losses and gains in hepatocellular carcinoma.
AB  - We examined the chromosomal changes of 22 hepatocellular carcinomas (HCCs) by
      comparative genomic hybridization (CGH) analysis and compared the results with
      that of allelotype by polymerase chain reaction based loss of heterozygosity (PCR
      LOH) analysis. By CGH analysis, frequent chromosomal losses were noted in the
      chromosomal region of 4q (59%), 8p (77%), and 16q (50%), whereas gains were noted
      in 1q (86%) and 8q (77%). All of these chromosomal arms were revealed to have
      frequent allelic imbalances by PCR-LOH analysis, however, 9% of chromosomal
      aberrations were detected only by CGH analysis and 2% were detected only by PCR
      LOH analysis. Our results suggest that CGH analysis gives more precise results
      for the screening of chromosomal aberrations in HCCs than that of PCR-LOH
      analysis with randomly selected microsatellite markers.

PMID- 12048167
TI  - On the occurrence of Leydig cell tumors in the F344 rat.
AB  - Dunning began inbreeding, what is now the Fischer F344 rat, in 1931. Because of
      her publications showing a low incidence of spontaneous tumors to 35 months of
      age, we selected the F344 rat for most of the studies in the National Cancer
      Institute (NCI) Bioassay Program, beginning in 1964. We were surprised by the
      finding that untreated male F344 rats displayed a high incidence of Leydig cell
      tumors of the testes beginning at about 17 months of age. The key difference
      between the results of Dunning and the NCI Bioassay Program was that her animals
      were retired breeders, whereas the NCI studies utilized virgin rats. The question
      of breeding was, therefore, examined as a possible protective factor. Groups of
      male F344 CDF/Crl rats were kept as virgin animals, or permitted access to
      bilaterally tube ligated female F344/Crl rats that were replaced twice over a 52
      week period. At that time, all males from both groups were housed three per cage
      to 85 weeks when they were killed in a CO(2) atmosphere and necropsied. Sections
      were prepared from the fixed tissues, stained and studied by histopathology. The
      results were evaluated by appropriate statistical methods. Virgin and sexually
      active F344 rats displayed monolateral or bilateral Leydig cell tumors. There was
      no statistical difference between the two groups. Despite the early difference
      between breeding and virgin F344 rats, a control experiment failed to disclose an
      effect of sexual activity on the occurrence of Leydig cell cancers. This disease
      displays some difference in incidence in various parts of the world, with the
      higher socioeconomic groups having a greater incidence. Etiological factors on
      the occurrence of this disease in animals and in humans remain to be discovered.

PMID- 12048166
TI  - Morphological and biological heterogeneity of three tumorigenic cell lines
      derived from a single p53-/- osteoblast-like cell line, MMC2.
AB  - Osteosarcoma is a malignant tumor with heterogeneous features both in
      histological and biological aspects. We have established three tumorigenic cell
      lines, MMOS1, MMOS2, and MMOS3, from three independent tumors that developed in
      nude mice after the inoculation of MMC2, an osteoblast-like cell line derived
      from p53-/- mice. Expression patterns of the osteoblast-related genes showed a
      marked difference between MMOS2 and the other two cell lines, and were correlated
      well with the features of the original tumors, ranging from an osteoblastic
      osteosarcoma (MMOS2) to tumors with scarce or no osteoid formation (MMOS1 and
      MMOS3). The properties of malignant cells also varied in the three cell lines.
      MMOS1, which was the most serum-dependent in vitro, developed markedly larger
      tumors in vivo than the other two cell lines. MMOS3 showed the fastest growth in
      low-serum conditions and produced the largest number of colonies in soft agar,
      but did not develop lung metastases, whereas MMOS1 and MMOS2 developed lung
      metastases with a frequency of 30 and 50%. These data suggest that the biological
      activities in vivo do not necessarily reflect those in vitro. Because the three
      tumorigenic cell lines share MMC2 as a common precursor, our data showed an
      example that the heterogeneity of osteosarcoma was created by genetic alterations
      that took place during the transformation process of each tumor.

PMID- 12048168
TI  - The relationship between (99m)Tc-MIBI uptakes and tumor cell death/proliferation
      state under irradiation.
AB  - To evaluate the potential of 99mTc-MIBI imaging to monitor cellular viability of
      tumor post-irradiation, Ehrlich carcinoma tissues were exposed to 60Co at
      different single dose (0, 5, 10, 15 and 20 Gy, respectively) and the following
      protocol were performed at 6 h pre-irradiation and 24, 72 and 144 h post
      irradiation, respectively: (1) 99mTc-MIBI planar scintigraphy was performed.
      Uptake of 99mTc-MIBI was expressed as differential uptake ratio (DUR) and tumor
      to-non-target ratio (T/NT). (2) Apoptosis index (AI), percent of necrosis area
      (PNA) and Proliferating cell nuclear antigen integral absorbance (PCNA-IA)were
      measured. DUR and T/NT decreased with radiation dose escalating and post
      irradiation time prolonging. At 24 h post-irradiation, DUR or T/NT was inversely
      correlated with AI or PNA (r=-0.849, -0.829, -0.883, -0.855, respectively, n=33,
      P<0.01) and positively correlated with PCNA-IA (r=0.789, 0.742, respectively,
      n=33, P<0.01). At 72 and 144 h post-irradiation, DUR or T/NT was only inversely
      correlated with PNA (r=-0.967, -0.956, -0.915, -0.886, respectively, n=33,
      P<0.01). It is suggested that 99mTc-MIBI uptake of tumor cell correlated with the
      changes of cell viability after irradiation. 99mTc-MIBI imaging may be a
      potential method to monitor tumor cell viability or therapeutic response after
      irradiation.

PMID- 12048169
TI  - Deep layer prefrontal cortex unit discharge in a cue-controlled open-field
      environment in the freely-moving rat.
AB  - The activity of single units in prefrontal cortex (prelimbic and anterior
      cingulate subregions) was recorded as rats performed a 'pellet-chasing' task in a
      cue-controlled, open-field environment in which the position of a single salient
      cue card was manipulated. Spike train analyses revealed three different types of
      unit. The first type was characterized by rhythmic bursts of spiking with inter
      burst intervals of approximately 200 ms (66% of units), the second by bursts with
      inter-burst intervals of approximately 80 ms (33% of units), and the third by non
      rhythmic firing characteristics (33% of units). None of the units had spatially
      selective firing characteristics, nor were their discharge patterns affected by
      manipulation of the cue card. Instead, the firing of the units had multiple
      behavioural correlates that occurred as the rat explored the environment. These
      results are in line with previous studies that suggest that prefrontal cortex
      unit discharge is not related to spatial processing but to behaviours necessary
      for exploration.

PMID- 12048170
TI  - Daily infusion of melatonin entrains circadian activity rhythms in the diurnal
      rodent Arvicanthis ansorgei.
AB  - The effect of exogenous melatonin (MEL) on the circadian system in nocturnal
      species has been extensively studied, but little is known about its chronobiotic
      effect in diurnal mammals. The present study investigated the effect of exogenous
      MEL on the circadian locomotor activity rhythm in the diurnal rodent Arvicanthis
      ansorgei. Male animals (n=34) were fitted with a subcutaneous catheter for daily
      infusion of MEL (1 h; 100 microg) and their running wheel activity was recorded.
      The results showed that administration of MEL to animals free-running in DD
      entrained their activity rhythm by phase advances at circadian time (CT) 10.62,
      and by phase delays at CT -0.40 (CT 0, activity onset). The range of entrainment
      was 17 and 11.5 min for advance and delay stimuli, respectively. Interestingly,
      in the nocturnal rat and the A. ansorgei, entrainment of the activity rhythm to
      exogenous MEL by phase advances occurs at exactly the same phase of the circadian
      cycle. In both nocturnal and diurnal species, the sensitivity window for
      exogenous MEL is located near the activity/rest transition points. It is
      concluded that the functional properties of entrainment to exogenous MEL are
      similar to those of other nonphotic stimuli. Furthermore, A. ansorgei might be an
      interesting animal model for studies on the chronobiotic effects of exogenous MEL
      in diurnal mammals including humans.

PMID- 12048171
TI  - Anabolic androgenic steroid affects competitive behaviour, behavioural response
      to ethanol and brain serotonin levels.
AB  - The present study investigated whether anabolic androgenic steroid (AAS)
      treatment (daily subcutaneous injections during 2 weeks with nandrolone
      decanoate; 15 mg/kg) affects competitive behaviour, and locomotor activity
      response to a sedative dose of ethanol (0.5 g ethanol/kg). In addition, levels of
      brain monoamines were assessed. The results showed that AAS treated animals
      exhibited enhanced dominant behaviour in the competition test compared to
      controls. The AAS groups' locomotor activity was not affected by ethanol in
      contrast to the controls who showed a sedative locomotor activity. AAS animals
      had significant lower levels of serotonin in basal forebrain and dorsal striatum
      compared to controls. These findings further strengthen the fact that AAS affects
      behaviour, as well as biochemical parameters. Based on previous studies and
      results from the present study, we hypothesize that AAS abuse may constitute a
      risk factor for disinhibitory behaviour, partly by affecting the serotonergic
      system.

PMID- 12048172
TI  - Social change affects the survival of new neurons in the forebrain of adult
      songbirds.
AB  - Many new neurons are added to the adult avian brain. Most of them die 3-5 weeks
      after they are born (Nature (Lond.) 335 (1988) 353; J. Comp. Neurol 411 (1999)
      487). Those that survive replace, numerically, older ones that have died (Neuron
      25 (2000) 481). It has been suggested that the new neurons enhance the brain's
      ability to acquire new long-term memories (review in Sci. Am. 260 (1989) 74). If
      so, perhaps an increase in social complexity affects the survival of new neurons
      in a social species. To test this hypothesis, we treated adult zebra finches
      (Taeniopygia guttata) with [3H]-thymidine immediately before introducing them
      into one of three different social environments that differed in complexity and
      killed them 40 days later. There was a significant difference between
      experimental groups in the number of [3H]-labeled neurons in neostriatum caudale
      (NC), high vocal center (HVC) and Area X, three forebrain regions that are
      involved in vocal communication. In these regions, birds placed in a large
      heterosexual group had more new neurons than birds kept singly or as male-female
      pairs. Regulation of new neuron survival by extent of circuit use may be a
      general mechanism for ensuring that neuronal replacement is closely attuned to
      environmental change.

PMID- 12048173
TI  - Metabotropic glutamate receptors in the hippocampus and nucleus accumbens are
      involved in generating seizure-induced hippocampal gamma waves and behavioral
      hyperactivity.
AB  - The involvement of metabotropic glutamate receptor (mGluR) subtypes in the
      generation of hippocampal EEG (30-100 Hz) and behaviors induced by a hippocampal
      afterdischarge (AD) was examined in freely behaving rats. A hippocampal AD
      induced an increase in gamma waves (30-100 Hz) for 20 min, accompanied by
      behavioral hyperactivity. Bilateral intracerebroventricular (i.c.v.) infusion of
      (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR
      antagonist, 30 min before a hippocampal AD, significantly suppressed both the
      increase in gamma waves and the behavioral hyperactivity. The hippocampal theta
      rhythm, the spontaneous hippocampal gamma waves, and evoked field potential
      oscillations of approximately 40 Hz were not affected by MCPG. Pre-infusion
      (i.c.v.) of (2S)-alpha-ethylglutamic acid (EGLU; a group II mGluR antagonist),
      but not (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; a group I mGluR
      antagonist), suppressed the postictal increase of both hippocampal gamma waves
      and behaviors. MCPG was infused locally into different brain structures in order
      to specify its target sites. Intra-hippocampal infusion of MCPG, or EGLU, blocked
      the increase in both gamma waves and behaviors. Infusion of MCPG into the nucleus
      accumbens suppressed the postictal behavioral hyperactivity without affecting the
      increase in hippocampal gamma waves. MCPG injected into the medial septum blocked
      neither postictal gamma activity nor behavioral hyperactivity. It is suggested
      that the group II mGluRs in the hippocampus are involved in generation of the
      postictal hippocampal gamma waves, while behavioral hyperactivity is partly
      mediated by mGluRs in the nucleus accumbens. However, spontaneous gamma and theta
      waves in the normal hippocampus are not mediated by mGluRs.

PMID- 12048174
TI  - Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery.
AB  - Mice received cytotoxic lesions which selectively removed all of the hippocampus
      and dentate gyrus except the most ventral portions. They were impaired on both
      spontaneous and rewarded discrete-trial alternation in T-mazes. Acquisition of
      reference memory for the location of a hidden platform in the Morris water maze
      was impaired in lesioned mice. On an elevated Y-maze reference memory task, in
      which only one arm was rewarded, lesioned mice showed no evidence of learning. In
      a Lashley III maze task, however, where maze rotation demonstrated that control
      performance was independent of distal spatial cues, acquisition in the lesioned
      mice was unimpaired. Control levels of continuous spontaneous alternation in a Y
      maze were too low to reveal a hippocampal deficit. A small impairment in
      acquisition of a multiple-trial passive avoidance task was seen in lesioned mice,
      despite a small but significant increase in reactivity to the footshock. These
      results are largely consistent with findings in hippocampal lesioned rats on the
      same or similar tasks, and reflect a major impairment of spatial cognition, with
      relative sparing of non-spatial task performance.

PMID- 12048175
TI  - Effect of excitotoxic lesions of rat medial prefrontal cortex on spatial memory.
AB  - The involvement of medial prefrontal cortex (mPFC) in spatial learning was
      examined in two memory tasks using spatial components, the Morris water maze and
      the three-panel runway. Using the Morris water maze task, with an invisible
      platform, the effects of NMDA mPFC lesions were assessed in a procedure
      reflecting spatial learning and memory, including a spatial reversal. In the
      three-panel runway, a delayed matching-to-position procedure was used in which
      rats were required to find food at the end of the runway after passing through
      one of three panel gates set into four barriers spaced equally apart along the
      maze. In addition, mPFC lesions were assessed behaviorally in two behavioral
      tests known to be sensitive to mPFC dysfunction: the food hoarding paradigm and
      spontaneous locomotion in the open field. Consistent with the documented effects
      of mPFC damage, NMDA mPFC lesions impaired food hoarding behavior and increased
      spontaneous exploratory locomotion. In the Morris water maze and the three-panel
      runway, mPFC-lesioned rats showed relatively few effects, supporting the
      conclusion that the damage inflicted to the mPFC had no consequence for the
      processing of spatial information. However, mPFC lesioned animals showed slower
      acquisition during both the training trial in the three-panel runway and the
      reversal training in the Morris water maze. These results suggest that spatial
      memory did not depend on mPFC integrity in the Morris water maze and the three
      panel runway experiments, and address the issue of deficits induced by mPFC
      lesions in memory tasks dependent on non-mnemonic processes such as attentional
      processes and/or a reduced behavioral flexibility to environmental changes.

PMID- 12048176
TI  - Association between experience of aggression and anxiety in male mice.
AB  - The sensory contact technique increases aggressiveness in male mice and allows an
      aggressive type of behavior to be formed as a result of repeated experience of
      social victories in daily agonistic confrontations. In the low aggressive and
      high emotional mice of CBA/Lac strain, repeated positive fighting experience
      leads to increased plus maze anxiety in the winners after 10 days of experience
      of victories and much more after 20 days. Behavioral reactivity to other
      conspecifics was significantly increased as revealed by the parameters of
      partition test, which measures aggressive motivation in the winners. Thus,
      anxiety as a consequence of repeated experience of aggression is associated with
      the increase of aggressive motivation in CBA/Lac mice. It is concluded, that: (1)
      Repeated experience of aggression provokes the development of anxiety in male
      mice. (2) The level of anxiety as well as its behavioral realization depends on
      the duration of aggressive experience and genetic strain. Genetically defined
      features of innate anxiety (trait or state) in individuals may determine the kind
      of association between aggressive experience, aggressive motivation and anxiety.

PMID- 12048177
TI  - Circadian modulation of learning and memory in fear-conditioned mice.
AB  - Endogenous processes referred to as circadian oscillators generate many of the
      daily rhythms in physiology and behavior of a variety of animals including
      humans. We investigated the possible circadian regulation of acquisition, recall
      and extinction in two strains of mice (C-57/6J and C-3H). Mice were trained in
      either the day or night with a tone and context fear conditioning protocol. The
      mice were then tested over the course of several days for their ability to recall
      the training. When comparing the performance of animals in the day and night, the
      mice acquired the conditioning faster in the day than in the night. Furthermore,
      the recall for context and tone consistently peaked during the day for at least 3
      days after training, irrespective of the time of training. Finally, the loss of
      this training (or extinction) exhibited a rhythm in that mice trained in night
      exhibited a greater degree of extinction than mice trained in the day. For all of
      these rhythms in acquisition, recall, and extinction the phase of the rhythm was
      controlled by the prior light-dark (LD) cycle. When we reversed the phase of the
      LD cycle, the phase of the rhythm also reversed. Importantly, all three of the
      rhythms also continued in constant darkness demonstrating the endogenous, and
      presumably circadian nature, of the rhythms.

PMID- 12048178
TI  - Orienting visuospatial attention generates manual reaction time asymmetries in
      target detection and pointing.
AB  - Right-handers exhibit a left hand advantage in response preparation when pointing
      to targets. These manual asymmetries are generally attributed to a right
      hemisphere specialization for spatial processing. More precisely, the left hand
      reaction time (RT) advantage was recently supposed to reflect specifically the
      right hemisphere superiority for movement planning. This study proposes to
      investigate a possible attentional origin for manual RT asymmetries. In a first
      experiment, we used the covert orienting of attention paradigm to measure
      subjects' RTs when reaching at targets (pointing task) both in valid, neutral and
      invalid conditions, either in the left or in the right visual fields and with the
      left and the right hand. In a second experiment, we applied the same paradigm to
      a detection task (key-pressing). Results revealed that orienting of attention to
      spatial locations was more time consuming when responding with the right than
      with the left hand, whether movement planning was required or not. It is
      suggested that the right hemisphere dominance for orienting of visuospatial
      attention account, partly at least, for the RT asymmetries classically observed
      in manual aiming.

PMID- 12048179
TI  - T-lymphocyte epitope identification and their use in vaccine development for HIV
      1.
AB  - Cellular immune responses mediated by CD8+ cytotoxic T-lymphocytes (CTL) and CD4+
      helper T-lymphocytes (HTL) are needed to effectively control and clear many viral
      pathogens, including HIV-1. Thus, vaccines for HIV-1 capable of inducing CTL and
      HTL responses are now the focus of multiple academic and industry-based research
      and development programs. The use of defined, minimal CTL and HTL epitopes in
      vaccines has several potential advantages. Firstly, it is possible to use
      epitopes that are conserved thus targeting the majority of viral variants within
      a given clade or across clades. Secondly, epitopes from multiple viral structural
      or accessory gene products can be included in vaccines, which supports the
      induction cellular immune responses with significant breadth. Finally, dominance
      relationships between epitopes can be altered to increase immune recognition of
      subdominant epitopes. HTL and CTL epitopes from HIV-1 have recently been
      identified and characterized in numbers that are large enough to support their
      use in experimental vaccines. Initial studies with prototype DNA vaccines
      encoding epitopes indicate the need to include intracellular targeting sequences,
      to direct the encoded gene products to different cellular compartments, and amino
      acid spacer sequences between epitopes to optimize the processing, and subsequent
      presentation, of individual epitopes. Vaccines composed of CTL or HTL epitopes
      are now being developed for clinical testing.

PMID- 12048180
TI  - FOXO forkhead transcription factors induce G(2)-M checkpoint in response to
      oxidative stress.
AB  - Members of the FOXO family of mammalian forkhead transcription factors, including
      AFX, FKHRL1, and FKHR, are homologs of DAF-16, which regulates genes that
      contribute both to longevity and to resistance to various stresses (including
      oxidative stress) in Caenorhabditis elegans. We have generated mouse myoblastic
      C2C12 cell lines in which expression of a constitutively active form of AFX (AFX
      TM) is inducible by Cre-mediated recombination at loxP sites. Here we show that
      forced expression of AFX-TM blocked cell cycle progression at the G(1) and G(2)
      phases and that FOXO family members regulated the expression of stress-inducible
      genes such as GADD45. AFX and FKHRL1 each directly activated the GADD45 promoter
      through interaction with FOXO binding motifs. Oxidative stress activated the
      GADD45 promoter in a FOXO-dependent manner, resulting in an increased abundance
      of GADD45 mRNA and protein as well as G(2) arrest. These responses were evident
      in cells in which the tumor suppressor protein p53 was inactivated. Our results
      suggest that the FOXO family of transcription factors plays an important role in
      the regulation of GADD45 in response to oxidative stress and thereby contributes
      to G(2)-M checkpoint.

PMID- 12048181
TI  - Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by
      the Aurora B Kinase stimulates Aurora B kinase activity.
AB  - How the events of mitosis are coordinated is not well understood. Intriguing
      mitotic regulators include the chromosomal passenger proteins. Loss of either of
      the passengers inner centromere protein (INCENP) or the Aurora B kinase results
      in chromosome segregation defects and failures in cytokinesis. Furthermore,
      INCENP and Aurora B have identical localization patterns during mitosis and
      directly bind each other in vitro. These results led to the hypothesis that
      INCENP is a direct substrate of Aurora B. Here we show that the Caenorhabditis
      elegans Aurora B kinase AIR-2 specifically phosphorylated the C. elegans INCENP
      ICP-1 at two adjacent serines within the carboxyl terminus. Furthermore, the full
      length and a carboxyl-terminal fragment of ICP-1 stimulated AIR-2 kinase
      activity. This increase in AIR-2 activity required that AIR-2 phosphorylate ICP-1
      because mutation of both serines in the AIR-2 phosphorylation site of ICP-1
      abolished the potentiation of AIR-2 kinase activity by ICP-1. Thus, ICP-1 is
      directly phosphorylated by AIR-2 and functions in a positive feedback loop that
      regulates AIR-2 kinase activity. Since the Aurora B phosphorylation site within
      INCENP and the functions of INCENP and Aurora B have been conserved among
      eukaryotes, the feedback loop we have identified is also likely to be
      evolutionarily conserved.

PMID- 12048182
TI  - Regulation of Raf-Akt Cross-talk.
AB  - We have recently shown that the Ras-Raf-MEK-ERK and phosphatidylinositol 3-kinase
      (PI3K)-Akt signaling pathways can cross-talk in the human breast cancer cell line
      MCF-7. High Raf activity induces growth arrest and differentiation in these
      cells, whereas high PI3K/Akt activity correlates with cell survival and
      proliferation. Here we show that the Raf-Akt cross-talk is regulated in a
      concentration- and ligand-dependent manner. High doses of insulin-like growth
      factor I (IGF-I) activate Akt quickly and strongly enough to suppress Raf kinase
      activity via phosphorylation of Ser-259, whereas low doses of IGF-I do not
      trigger this cross-talk but are still mitogenic. Phorbol 12-myristate 13-acetate,
      a differentiation-inducing stimulus, potently activates the Ras-Raf-MEK-ERK
      pathway but only weakly activates PI3K/Akt and does not trigger the cross-talk.
      Thus, the herein analyzed parameters such as ligand type, concentration, and time
      course may contribute to the cellular response of either proliferation or
      differentiation. This is highly relevant to understanding cellular transformation
      and may be of use in areas like tissue engineering.

PMID- 12048183
TI  - Specific phosphorylation of exogenous protein and peptide substrates by the human
      cytomegalovirus UL97 protein kinase. Importance of the P+5 position.
AB  - Human cytomegalovirus UL97 is an unusual protein kinase that can phosphorylate
      nucleoside analogs such as ganciclovir but whose specificity for exogenous
      protein substrates has remained unknown. We found that purified, recombinant
      glutathione S-transferase-UL97 fusion protein can phosphorylate histone H2B.
      Phosphorylation was abrogated by substitution of glutamine for a conserved lysine
      in subdomain II and inhibited by a new antiviral drug, maribavir. Sequencing and
      mass spectrometric analyses of purified (32)P-labeled tryptic peptides of H2B
      revealed that the sites of phosphorylation were, in order of extent, Ser-38, Ser
      87, Ser-6, Ser-112, and Ser-124. Phosphorylation of synthetic peptides containing
      these sites, analyzed using a new, chimeric gel system, correlated with their
      phosphorylation in H2B. Phosphorylation of the Ser-38 peptide by UL97 occurred on
      Ser-38 and was specifically sensitive to maribavir, whereas phosphorylation of
      this peptide by cAMP-dependent protein kinase occurred on Ser-36. The extent of
      phosphorylation was greatest with peptides containing an Arg or Lys residue 5
      positions downstream (P+5) from the Ser. Substitution with Ala at this position
      essentially eliminated activity. These results identify exogenous protein and
      peptide substrates of UL97, reveal an unusual dependence on the P+5 position, and
      may abet discovery of new inhibitors of UL97 and human cytomegalovirus
      replication.

PMID- 12048184
TI  - Kinetic and affinity predictions of a protein-protein interaction using
      multivariate experimental design.
AB  - We measured the influence of 14 mutations and 5 environmental variables (buffer
      perturbation) on the association and dissociation rate of a camel single domain
      antibody (cAb-Lys3) interacting with hen egg white lysozyme using a surface
      plasmon resonance-based biosensor. Based on this data set, we constructed
      quantitative predictive models for both kinetic (k(a) and k(d)) constants as for
      the affinity constant (K(d)). Mutations, after parameterization by quantitative
      descriptors, and buffers were selected using multivariate experimental design.
      These models were able to predict the corresponding parameters of four new
      variants of cAb-Lys3. Moreover, the models provide insights to the important
      chemical aspects of the interacting residues, which are difficult to deduce from
      the crystal structure. Our approach provides useful physicochemical information
      of protein-protein interactions in general. The information obtained from this
      kind of analysis complements and goes beyond that of conventional methods like
      alanine scanning and substitution by closely related amino acids. The
      mathematical modeling may contribute to a rational approach in the optimization
      of bio-molecules of biotechnological interest.

PMID- 12048185
TI  - Structural basis and mechanism of the inhibition of the type-3 copper protein
      tyrosinase from Streptomyces antibioticus by halide ions.
AB  - The inhibition of the type-3 copper enzyme tyrosinase by halide ions was studied
      by kinetic and paramagnetic (1)H NMR methods. All halides are inhibitors in the
      conversion of l-3,4-dihydroxyphenylalanine (l-DOPA) with apparent inhibition
      constants that follow the order I(-) < F(-) << Cl(-) < Br(-) at pH 6.80. The
      results show that the inhibition arises from the interaction of halide with both
      the oxidized (affinity F(-) > Cl(-) > Br(-) >> I(-)) and reduced (affinity I(-) >
      Br(-) > Cl(-) >> F(-)) enzyme. The paramagnetic (1)H NMR of the oxidized enzyme
      complexed with the halides is consistent with a direct interaction of halide with
      the type-3 site and shows that the (Cu-His(3))(2) coordination occurs in all
      halide-bound species. It is surmised that halides bridge both of the copper ions
      in the active site. Fluoride and chloride are shown to bind only to the low pH
      form of oxidized tyrosinase, explaining the strong pH dependence of the
      inhibition by these ions. We further show that p-toluic acid and the bidentate
      transition state analogue, Kojic acid, displace chloride from the oxidized active
      site, whereas the monodentate substrate analogue, p-nitrophenol, forms a ternary
      complex with the enzyme and the chloride ion. On the basis of the experimental
      results, a model is formulated for the inhibitor action and for the reaction of
      diphenols with the oxidized enzyme.

PMID- 12048186
TI  - Control of mitotic exit in budding yeast. In vitro regulation of Tem1 GTPase by
      Bub2 and Bfa1.
AB  - The elimination of mitotic kinase activity at the end of mitosis is essential for
      progression to the next stage of the eukaryotic cell cycle. In budding yeast,
      this process is controlled by a regulatory cascade called the mitotic exit
      network. Extensive genetic data indicate that mitotic exit network activity is
      determined by a GTP-binding protein, Tem1, and its putative regulators, Bub2,
      Bfa1, and Lte1. Here we describe the purification and in vitro activities of
      Tem1, Bub2, and Bfa1. We describe the nucleotide binding properties of Tem1 and
      characterize its intrinsic GTPase activity. The combination of Bfa1 and Bub2 acts
      as a two-component GTPase-activating protein for Tem1. In the absence of Bub2,
      Bfa1 inhibits the GTPase and GTP exchange activities of Tem1. This inhibition is
      elicited by either the N- or C-terminal regions of Bfa1, which also retain some
      ability to co-activate GTPase activity in the presence of Bub2. Although the C
      terminal region of Bfa1 binds to Bub2, no interaction of the N-terminal half of
      Bfa1 with Bub2 was detected despite their combined GAP activity. Therefore, we
      propose that Bfa1 acts both as an adaptor to connect Bub2 and Tem1 and as an
      allosteric effector that facilitates this interaction.

PMID- 12048187
TI  - Crystal structure of type II peptide deformylase from Staphylococcus aureus.
AB  - The first crystal structure of Class II peptide deformylase has been determined.
      The enzyme from Staphylococcus aureus has been overexpressed and purified in
      Escherichia coli and the structure determined by x-ray crystallography to 1.9 A
      resolution. The purified iron-enriched form of S. aureus peptide deformylase
      enzyme retained high activity over many months. In contrast, the iron-enriched
      form of the E. coli enzyme is very labile. Comparison of the two structures
      details many differences; however, there is no structural explanation for the
      dramatic activity differences we observed. The protein structure of the S. aureus
      enzyme reveals a fold similar, but not identical to, the well characterized E.
      coli enzyme. The most striking deviation of the S. aureus from the E. coli
      structure is the unique conformation of the C-terminal amino acids. The
      distinctive C-terminal helix of the latter is replaced by a strand in S. aureus
      which wraps around the enzyme, terminating near the active site. Although there
      are no differences at the amino acid level near the active site metal ion,
      significant changes are noted in the peptide binding cleft which may play a role
      in the design of general peptide deformylase inhibitors.

PMID- 12048188
TI  - Crystal structure of bacterial morphinone reductase and properties of the C191A
      mutant enzyme.
AB  - The crystal structure of the NADH-dependent bacterial flavoenzyme morphinone
      reductase (MR) has been determined at 2.2-A resolution in complex with the
      oxidizing substrate codeinone. The structure reveals a dimeric enzyme comprising
      two 8-fold beta/alpha barrel domains, each bound to FMN, and a subunit folding
      topology and mode of flavin-binding similar to that found in Old Yellow Enzyme
      (OYE) and pentaerythritol tetranitrate (PETN) reductase. The subunit interface of
      MR is formed by interactions from an N-terminal beta strand and helices 2 and 8
      of the barrel domain and is different to that seen in OYE. The active site
      structures of MR, OYE, and PETN reductase are highly conserved reflecting the
      ability of these enzymes to catalyze "generic" reactions such as the reduction of
      2-cyclohexenone. A region of polypeptide presumed to define the reducing coenzyme
      specificity is identified by comparison of the MR structure (NADH-dependent) with
      that of PETN reductase (NADPH-dependent). The active site acid identified in OYE
      (Tyr-196) and conserved in PETN reductase (Tyr-186) is replaced by Cys-191 in MR.
      Mutagenesis studies have established that Cys-191 does not act as a crucial acid
      in the mechanism of reduction of the olefinic bond found in 2-cyclohexenone and
      codeinone.

PMID- 12048189
TI  - Studies of a positive supercoiling machine. Nucleotide hydrolysis and a
      multifunctional "latch" in the mechanism of reverse gyrase.
AB  - Reverse gyrase, the only topoisomerase known to positively supercoil DNA, has an
      N-terminal ATPase domain that drives the activity of a topoisomerase domain. This
      study shows that the N-terminal domain represses topoisomerase activity in the
      absence of nucleotide, and nucleotide binding is sufficient to relieve the
      repression. A "latch" region in the N-terminal part was observed to close over
      the topoisomerase domain in the reverse gyrase crystal structure. Mutants lacking
      all or part of the latch relax DNA in the absence of nucleotide, indicating that
      this region mediates topoisomerase repression. The mutants also show altered DNA
      dependent ATPase activity, suggesting that the latch may be involved in coupling
      nucleotide hydrolysis to supercoiling. It is not required for this process,
      however, because the mutants can still positively supercoil DNA. Nucleotide
      hydrolysis is essential to the specificity of reverse gyrase for increasing the
      linking number of DNA. Although with ATP the enzyme performs strand passage
      always toward increasing linking number, it can increase or decrease the linking
      number in the presence of a nonhydrolyzable ATP analog. This suggests that the
      mechanism of reverse gyrase is best described by a combination of recently
      proposed models.

PMID- 12048190
TI  - Arginine/lysine-rich nuclear localization signals mediate interactions between
      dimeric STATs and importin alpha 5.
AB  - Interferon stimulation results in tyrosine phosphorylation, dimerization, and
      nuclear import of STATs (signal transducers and activators of transcription).
      Proteins to be targeted into the nucleus usually contain nuclear localization
      signals (NLSs), which interact with importin alpha. Importin alpha binds to
      importin beta, which docks the protein complex to nuclear pores, and the complex
      translocates into the nucleus. Here we show that baculovirus-produced and 
      activated STAT1 homodimers and STAT1-STAT2 heterodimers directly interacted with
      importin alpha 5 (NPI-1). This interaction was very stable and was dependent on
      lysines 410 and 413 of STAT1. Only STAT dimers that had two intact NLS elements,
      one in each monomer, were able to bind to importin alpha 5. STAT-importin alpha 5
      complexes apparently consisted of two STAT and two importin alpha molecules. STAT
      NLS-dependent colocalization of importin alpha 5 with STAT1 or STAT2 was seen in
      the nucleus of transfected cells. gamma-Activated sequence DNA elements
      efficiently inhibited STAT binding to importin alpha 5 suggesting that the DNA
      and importin alpha binding sites are close to each other in STAT dimers. Our
      results demonstrate that specific NLSs in STATs mediate direct interactions of
      STAT dimers with importin alpha, which activates the nuclear import process.

PMID- 12048191
TI  - Nongenomic testosterone calcium signaling. Genotropic actions in androgen
      receptor-free macrophages.
AB  - Steroid hormones exert genotropic actions through members of the nuclear receptor
      family. Here, we have demonstrated genotropic actions of testosterone that are
      independent of intracellular androgen receptors (iAR). Through plasma membrane
      androgen receptors (mAR), testosterone induces a rapid rise in the intracellular
      free Ca(2+) concentration of iAR-free murine RAW 264.7 macrophages. This
      nongenomic testosterone signaling, which is independent of both iAR and estrogen
      receptors, does not in itself activate either the mitogen-activated protein
      kinase (MAPK) families ERK1/2, p38, and JNK/SAPK, the stably and transiently
      transfected c-fos promoter, or NO production. In the context of
      lipopolysaccharide (LPS) signaling, however, testosterone attenuates LPS
      activation of the c-fos promoter and NO production, which is abolished by the
      intracellular Ca(2+) chelator BAPTA. Testosterone also attenuates the LPS
      activation of p38 but not that of ERK1/2 and JNK/SAPK, and this attenuation is
      abrogated by BAPTA. Moreover, the p38 inhibitor, SB 203580, largely reduces LPS
      activation of the c-fos promoter and NO production, and the remaining levels are
      no longer regulated by testosterone. This study is the first to provide
      information on genotropic actions of mAR-mediated nongenomic testosterone Ca(2+)
      signaling by cross-talk with the LPS signaling pathway through p38 MAPK with
      impact on cell function.

PMID- 12048192
TI  - Mouse very long-chain acyl-CoA synthetase in X-linked adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder
      characterized by accumulation of very long-chain fatty acids (VLCFA). This
      accumulation has been attributed to decreased VLCFA beta-oxidation and
      peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity. The X-ALD gene,
      ABCD1, encodes a peroxisomal membrane ATP binding cassette transporter, ALDP,
      that is hypothesized to affect VLCS activity in peroxisomes by direct interaction
      with the VLCS enzyme. Recently, a VLCS gene that encodes a protein with
      significant sequence identity to known rat and human peroxisomal VLCS protein has
      been identified in mice. We find that the mouse VLCS gene (Vlcs) encodes an
      enzyme (Vlcs) with VLCS activity that localizes to peroxisomes and is expressed
      in X-ALD target tissues. We show that the expression of Vlcs in the peroxisomes
      of X-ALD mouse fibroblasts improves VLCFA beta-oxidation in these cells, implying
      a role for this enzyme in the biochemical abnormality of X-ALD. X-ALD mice, which
      accumulate VLCFA in tissues, show no change in the expression of Vlcs, the
      subcellular localization of Vlcs, or general peroxisomal VLCS activity. These
      observations imply that ALDP is not necessary for the proper expression or
      localization of Vlcs protein, and the control of VLCFA levels does not depend on
      the direct interaction of Vlcs and ALDP.

PMID- 12048193
TI  - Novel interaction between the M4 muscarinic acetylcholine receptor and elongation
      factor 1A2.
AB  - The activation of the muscarinic acetylcholine receptor (mAChR) family,
      consisting of five subtypes (M1-M5), produces a variety of physiological effects
      throughout the central nervous system. However, the role of each individual
      subtype remains poorly understood. To further elucidate signal transduction
      pathways for specific subtypes, we used the most divergent portion of the
      subtypes, the intracellular third (i3) loop, as bait to identify interacting
      proteins. Using a brain pull-down assay, we identify elongation factor 1A2
      (eEF1A2) as a specific binding partner to the i3 loop of M4, and not to M1 or M2.
      In addition, we demonstrate a direct interaction between these proteins. In the
      rat striatum, the M4 mAChR colocalizes with eEF1A2 in the soma and neuropil. In
      PC12 cells, endogenous eEF1A2 co-immunoprecipitates with the endogenous M4 mAChR,
      but not with the endogenous M1 mAChR. In our in vitro model, M4 dramatically
      accelerates nucleotide exchange of eEF1A2, a GTP-binding protein. This indicates
      the M4 mAChR is a guanine exchange factor for eEF1A2. eEF1A2 is an essential GTP
      binding protein for protein synthesis. Thus, our data suggest a novel role for M4
      in the regulation of protein synthesis through its interaction with eEF1A2.

PMID- 12048194
TI  - Adaptor protein Shc is an isoform-specific direct activator of the tyrosine
      kinase c-Src.
AB  - The activity of c-Src protein-tyrosine kinase is up-regulated under a number of
      receptor signaling pathways. However, the activation mechanism of c-Src under
      physiological conditions has remained unclear. We show here that the Shc adaptor
      protein is a novel direct activator of c-Src in epidermal growth factor receptor
      signaling in A431 human epidermoid carcinoma cells. Among the three Shc isoforms,
      P66 and P52, but not P46, were found to interact with and activate c-Src in vitro
      and in vivo. Activation of c-Src accompanied autophosphorylation of c-Src in the
      activation segment, but the carboxyl-terminal dephosphorylation was not observed.
      We have identified the interaction sites between Shc and c-Src and constructed a
      point mutant of Shc that abolishes the c-Src activation. Using this mutant, we
      have confirmed that the Shc-mediated c-Src activation triggers Stat-p21/WAF1/Cip1
      pathway that has been implicated in the cell cycle arrest and apoptosis of
      epidermal growth factor-stimulated A431 cells.

PMID- 12048195
TI  - Kinetic and structural analysis of a new group of Acyl-CoA carboxylases found in
      Streptomyces coelicolor A3(2).
AB  - Two acyl-CoA carboxylases from Streptomyces coelicolor have been successfully
      reconstituted from their purified components. Both complexes shared the same
      biotinylated alpha subunit, AccA2. The beta and the epsilon subunits were
      specific from each of the complexes; thus, for the propionyl-CoA carboxylase
      complex the beta and epsilon components are PccB and PccE, whereas for the acetyl
      CoA carboxylase complex the components are AccB and AccE. The two complexes
      showed very low activity in the absence of the corresponding epsilon subunits;
      addition of PccE or AccE dramatically increased the specific activity of the
      enzymes. The kinetic properties of the two acyl-CoA carboxylases showed a clear
      difference in their substrate specificity. The acetyl-CoA carboxylase was able to
      carboxylate acetyl-, propionyl-, or butyryl-CoA with approximately the same
      specificity. The propionyl-CoA carboxylase could not recognize acetyl-CoA as a
      substrate, whereas the specificity constant for propionyl-CoA was 2-fold higher
      than for butyryl-CoA. For both enzymes the epsilon subunits were found to
      specifically interact with their carboxyltransferase component forming a beta
      epsilon subcomplex; this appears to facilitate the further interaction of these
      subunits with the alpha component. The epsilon subunit has been found genetically
      linked to several carboxyltransferases of different Streptomyces species; we
      propose that this subunit reflects a distinctive characteristic of a new group of
      acyl-CoA carboxylases.

PMID- 12048197
TI  - A molecular basis for stabilization of the von Hippel-Lindau (VHL) tumor
      suppressor protein by components of the VHL ubiquitin ligase.
AB  - The multiprotein von Hippel-Lindau (VHL) tumor suppressor (CBC(VHL), Cul2-Elongin
      BC-VHL) and SCF (Skp1-Cul1/Cdc53-F-box protein) complexes are members of
      structurally related families of E3 ubiquitin ligases that use a heterodimeric
      module composed of a member of the Cullin protein family and the RING finger
      protein Rbx1 (ROC1/Hrt1) to activate ubiquitylation of target proteins by the E2
      ubiquitin-conjugating enzymes Ubc5 and Cdc34. VHL and F-box proteins function as
      the substrate recruitment subunits of CBC(VHL) and SCF complexes, respectively.
      In cells, many F-box proteins are short lived and are proposed to be
      ubiquitylated by an autocatalytic mechanism and destroyed by the proteasome
      following assembly into SCF complexes. In contrast, the VHL protein is stabilized
      by interaction with the Elongin B and C subunits of CBC(VHL) in cells. In this
      report, we have presented direct biochemical evidence that unlike the F-box
      protein Cdc4, which is ubiquitylated in vitro by Cdc34 in the context of the SCF,
      the VHL protein is protected from Ubc5-catalyzed ubiquitylation following
      assembly into the CBC(VHL) complex. CBC(VHL) is continuously required for
      negative regulation of hypoxia-inducible transcription factors in normoxic cells
      and of SCF complexes, many of which function only transiently during the cell
      cycle or in response to cellular signals. Our findings provide a molecular basis
      for the different modes of cellular regulation of VHL and F-box proteins and are
      consistent with the known roles of CBC(VHL).

PMID- 12048196
TI  - ILPIP, a novel anti-apoptotic protein that enhances XIAP-mediated activation of
      JNK1 and protection against apoptosis.
AB  - We have previously described a new aspect of the Inhibitor of Apoptosis (IAP)
      family of proteins anti-apoptotic activity that involves the TAK1/JNK1 signal
      transduction pathway (1,2). Our findings suggest the existence of a novel
      mechanism that regulates the anti-apoptotic activity of IAPs that is separate
      from caspase inhibition but instead involves TAK1-mediated activation of JNK1. In
      a search for proteins involved in the XIAP/TAK1/JNK1 signaling pathway we
      isolated by yeast two-hybrid screening a novel X chromosome-linked IAP (XIAP)
      interacting protein that we called ILPIP (hILP-Interacting Protein). Whereas
      ILPIP moderately activates JNK family members when expressed alone, it strongly
      enhances XIAP-mediated activation of JNK1, JNK2, and JNK3. The expression of a
      catalytically inactive mutant of TAK1 blocked XIAP/ILPIP synergistic activation
      of JNK1 thereby implicating TAK1 in this signaling pathway. ILPIP moderately
      protects against interleukin-1beta converting enzyme- or Fas-induced apoptosis
      and significantly potentiates the anti-apoptotic activity of XIAP. In vivo co
      precipitation experiments show that both ILPIP and XIAP interact with TAK1 and
      tumor necrosis factor receptor-associated factor 6. Finally, expression of ILPIP
      did not affect the ability of XIAP to inhibit caspase activation, further
      supporting the idea that XIAP protection against apoptosis is achieved by two
      separate mechanisms: one requiring JNK1 activation and a second involving caspase
      inhibition.

PMID- 12048198
TI  - Tropomyosin and gelsolin cooperate in controlling the microfilament system.
AB  - Tropomyosin has been shown to cause annealing of gelsolin-capped actin filaments.
      Here we show that tropomyosin is highly efficient in transforming even the
      smallest gelsolin-actin complexes into long actin filaments. At low
      concentrations of tropomyosin, the effect of tropomyosin depends on the length of
      the actin oligomer, and the cooperative nature of the process is a direct
      indication that tropomyosin induces a conformational change in the gelsolin-actin
      complexes, altering the structure at the actin (+) end such that capping by
      gelsolin is abolished. At increased concentrations of tropomyosin, heterodimers,
      trimers, and tetramers are converted to actin filaments. In addition, evidence is
      presented demonstrating that gelsolin, once removed from the (+) end of the
      actin, can reassociate with the newly formed tropomyosin-decorated actin
      filaments. Interestingly, the binding of gelsolin to the tropomyosin-actin
      filament complexes saturates at 2 gelsolin molecules per 14 actin and 2
      tropomyosins, i.e. two gelsolins per tropomyosin-regulatory unit along the
      filament. These observations support the view that both tropomyosin and gelsolin
      are likely to have important functions in addition to those proposed earlier.

PMID- 12048199
TI  - Cyclin D1 Is a Ligand-independent Co-repressor for Thyroid Hormone Receptors.
AB  - Thyroid hormone receptors (TRs) are critical regulators of growth,
      differentiation, and homeostasis. TRs function by regulating the expression of
      thyroid hormone (T3) target genes in both ligand-dependent and -independent
      pathways. Distinct classes of co-regulatory proteins modulate these two pathways.
      We show here a novel role of cyclin D1 as a T3-independent co-repressor for TRs.
      Cyclin D1 interacted with TR in vitro and in cells in a ligand-independent
      manner. Cyclin D1 acted to repress both the silencing activity of the unliganded
      TR and the transcriptional activity of the liganded TR. The repression was not
      due to the inhibition of the binding of TR to the thyroid hormone response
      element but by serving as a ligand-independent bridging factor to selectively
      recruit HDAC3 to form ternary complexes. The repression was augmented by
      increasing expression of HDAC3 but not by HDAC1 and was alleviated by
      trichostatin A. Thus, cyclin D1 is a novel ligand-independent co-repressor that
      opens a new paradigm to understand the molecular basis of the silencing action of
      TR.

PMID- 12048200
TI  - Rpf2p, an evolutionarily conserved protein, interacts with ribosomal protein L11
      and is essential for the processing of 27 SB Pre-rRNA to 25 S rRNA and the 60 S
      ribosomal subunit assembly in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae Rrs1p is a nuclear protein that is essential for the
      maturation of 25 S rRNA and the 60 S ribosomal subunit assembly. In two-hybrid
      screening, using RRS1 as bait, we have cloned YKR081c/RPF2. Rpf2p is essential
      for growth and is mainly localized in the nucleolus. The amino acid sequence of
      Rpf2p is highly conserved in eukaryotes from yeast to human. Similar to Rrs1p,
      Rpf2p shows physical interaction with ribosomal protein L11 and appears to
      associate with preribosomal subunits fairly tightly. Northern, methionine pulse
      chase, and sucrose density gradient ultracentrifugation analyses reveal that the
      depletion of Rpf2p results in a delayed processing of pre-rRNA, a decrease of
      mature 25 S rRNA, and a shortage of 60 S subunits. An analysis of processing
      intermediates by primer extension shows that the Rpf2p depletion leads to an
      accumulation of 27 SB pre-rRNA, suggesting that Rpf2p is required for the
      processing of 27 SB into 25 S rRNA.

PMID- 12048201
TI  - In situ phage screening. A method for identification of subnanogram tissue
      components in situ.
AB  - We have established a novel method, in situ phage screening (ISPS), to identify
      proteins in tissue microstructures. The method is based on the selection of
      repertoires of phage-displayed antibody fragments with small samples of tissues
      microdissected using a laser. Using a human muscle frozen section with an area of
      4800 microm2 as a model target, we successfully selected monoclonal antibody
      fragments directed against three major (myosin heavy chain, actin, and
      tropomyosin-alpha) and one minor (alpha-actinin 2) muscle constituent proteins.
      These proteins were present in the sample in amounts less than one nanogram, and
      the antibodies were used to visualize the proteins in situ. This shows that the
      use of ISPS can obtain monoclonal antibodies for histochemical and biochemical
      purposes against minute amounts of proteins from microstructures with no
      requirement for large amounts of samples or biochemical efforts.

PMID- 12048202
TI  - The polycystic kidney disease-1 promoter is a target of the beta-catenin/T-cell
      factor pathway.
AB  - Polycystic kidney disease (PKD) results from loss-of-function mutations in the
      PKD1 gene. There are also reports showing abnormally high levels of PKD1
      expression in cystic epithelial cells. At present, nothing is known about the
      molecular mechanisms regulating the normal expression of the PKD1 gene or whether
      transcriptional disregulation of the PKD1 gene has a role in cyst formation. We
      have analyzed a 3.3-kb 5'-proximal portion of the human PKD1 gene. Sequence
      analysis revealed the presence of consensus sequences for numerous
      transactivating factors, including four T-cell factor (TCF) binding elements
      (TBEs). Transcriptional activity of the 3.3-kb fragment and a series of deletion
      constructs was assayed in HEK293T cells. A 2.0-kb proximal promoter region
      containing one of the four TBEs (TBE1) was inducible up to 6-fold by
      cotransfection with beta-catenin. beta-catenin-mediated induction was inhibited
      by dominant-negative TCF and by deletion of the TBE1 sequence. 15- or 109-bp
      sequences containing the TBE1 site, when cloned upstream of a minimal promoter,
      were shown to respond to beta-catenin induction. Gel shift assays confirmed that
      the TBE1 site is capable of forming complexes with TCF and beta-catenin. To
      determine whether expression of the endogenous PKD1 gene responds to beta
      catenin, HT1080 cells were treated with LiCl, and HeLa cells were stably
      transfected with beta-catenin. In both cases, endogenous PKD1 mRNA levels were
      elevated in response to these treatments. Taken together, these studies define an
      active PKD1 promoter region and suggest that the PKD1 gene is a target of the
      beta-catenin/TCF pathway.

PMID- 12048203
TI  - Inhibition of JNK by cellular stress- and tumor necrosis factor alpha-induced
      AKT2 through activation of the NF kappa B pathway in human epithelial Cells.
AB  - Previous studies have demonstrated that AKT1 and AKT3 are activated by heat shock
      and oxidative stress via both phosphatidylinositol 3-kinase-dependent and 
      independent pathways. However, the activation and role of AKT2 in the stress
      response have not been fully elucidated. In this study, we show that AKT2 in
      epithelial cells is activated by UV-C irradiation, heat shock, and
      hyperosmolarity as well as by tumor necrosis factor alpha (TNFalpha) through a
      phosphatidylinositol 3-kinase-dependent pathway. The activation of AKT2 inhibits
      UV- and TNF alpha-induced c-Jun N-terminal kinase (JNK) and p38 activities that
      have been shown to be required for stress- and TNF alpha-induced programmed cell
      death. Moreover, AKT2 interacts with and phosphorylates I kappa B kinase alpha.
      The phosphorylation of I kappa B kinase alpha and activation of NF kappa B
      mediates AKT2 inhibition of JNK but not p38. Furthermore, phosphatidylinositol 3
      kinase inhibitor or dominant negative AKT2 significantly enhances UV- and TNF
      alpha-induced apoptosis, whereas expression of constitutively active AKT2
      inhibits programmed cell death in response to UV and TNFalpha -induced apoptosis
      by inhibition of stress kinases and provide the first evidence that AKT inhibits
      stress kinase JNK through activation of the NF kappa B pathway.

PMID- 12048204
TI  - Melanocyte-specific microphthalmia-associated transcription factor isoform
      activates its own gene promoter through physical interaction with lymphoid
      enhancing factor 1.
AB  - Waardenburg syndrome type 2 (WS2) is associated with heterozygous mutations in
      the gene encoding microphthalmia-associated transcription factor (MITF) and
      characterized by deafness and hypopigmentation due to lack of melanocytes in the
      inner ear and skin. Melanocyte-specific MITF isoform (MITF-M) is essential for
      melanocyte differentiation and is transcriptionally induced by Wnt signaling that
      is mediated by beta-catenin and LEF-1. Here we show that MITF-M transactivates
      its own promoter (M promoter) by interacting with LEF-1, as judged by transient
      expression assays and in vitro protein-protein binding assays, whereas no
      transactivation of the M promoter was detected with MITF-M alone or with the
      combination of MITF-M and dominant-negative LEF1 that lacks the beta-catenin
      binding domain. This synergy depends on the three LEF-1-binding sites that are
      clustered in the proximal M promoter. Importantly, MITF-M recruited on the M
      promoter could function as a non-DNA-binding cofactor for LEF-1. Thus, MITF-M may
      function as a self-regulator of its own expression to maintain a threshold level
      of MITF-M that is required for melanocyte development. We suggest that MITF-M
      haploinsufficiency may impair the dosage-sensitive role of MITF-M or the correct
      assembly of multiple transcription factors, involving MITF-M, on the M promoter,
      which could account for dominant inheritance of WS2.

PMID- 12048205
TI  - Distinct dimer interaction and regulation in nitric-oxide synthase types I, II,
      and III.
AB  - Homodimer formation activates all nitric-oxide synthases (NOSs). It involves the
      interaction between two oxygenase domains (NOSoxy) that each bind heme and (6R)
      tetrahydrobiopterin (H4B) and catalyze NO synthesis from L-Arg. Here we compared
      three NOSoxy isozymes regarding dimer strength, interface composition, and the
      ability of L-Arg and H4B to stabilize the dimer, promote its formation, and
      protect it from proteolysis. Urea dissociation studies indicated that the
      relative dimer strengths were NOSIIIoxy >> NOSIoxy > NOSIIoxy (endothelial NOSoxy
      (eNOSoxy) >> neuronal NOSOXY (nNOSoxy) > inducible NOSoxy (iNOSoxy)). Dimer
      strengths of the full-length NOSs had the same rank order as judged by their urea
      induced loss of NO synthesis activity. NOSoxy dimers containing L-Arg plus H4B
      exhibited the greatest resistance to urea-induced dissociation followed by those
      containing either molecule and then by those containing neither. Analysis of
      crystallographic structures of eNOSoxy and iNOSoxy dimers showed more
      intersubunit contacts and buried surface area in the dimer interface of eNOSoxy
      than iNOSoxy, thus revealing a potential basis for their different stabilities. L
      Arg plus H4B promoted dimerization of urea-generated iNOSoxy and nNOSoxy
      monomers, which otherwise was minimal in their absence, and also protected both
      dimers against trypsin proteolysis. In these respects, L-Arg alone was more
      effective than H4B alone for nNOSoxy, whereas for iNOSoxy the converse was true.
      The eNOSoxy dimer was insensitive to proteolysis under all conditions. Our
      results indicate that the three NOS isozymes, despite their general structural
      similarity, differ markedly in their strengths, interfaces, and in how L-Arg and
      H4B influence their formation and stability. These distinguishing features may
      provide a basis for selective control and likely help to regulate each NOS in its
      particular biologic milieu.

PMID- 12048206
TI  - Characterization of a hyperthermophilic P-type ATPase from Methanococcus
      jannaschii expressed in yeast.
AB  - We report on the biochemical and structural properties of a putative P-type H(+)
      ATPase, MJ1226p, from the anaerobic hyperthermophilic Archaea Methanococcus
      jannaschii. An efficient heterologous expression system was developed in
      Saccharomyces cerevisiae and a four-step purification protocol, using n-dodecyl
      beta-d-maltoside, led to a homogeneous detergent-solubilized protein fraction
      with a yield of over 2 mg of protein per liter of culture. The three-dimensional
      structure of the purified detergent-solubilized protein obtained at 2.4 nm
      resolution by electron microscopy showed a dimeric organization in which the size
      and the shape of each monomer was compatible with the reported structures of P
      type ATPases. The purified MJ1226p ATPase was inactive at 40 degrees C and was
      active at elevated temperature reaching high specific activity, up to 180
      micromol of P(i) x min(-1) x mg(-1) at 95 degrees C. Maximum ATPase activity was
      observed at pH 4.2 and required up to 200 mm monovalent salts. The ATPase
      activity was stable for several days upon storage at 65 degrees C and was highly
      resistant to urea and guanidine hydrochloride. The protein formed catalytic
      phosphoenzyme intermediates from MgATP or P(i), a functional characteristic
      specific of P-type ATPases. The highly purified, homogeneous, stable, and active
      MJ1226p ATPase provides a new model for further structure-function studies of P
      type ATPases.

PMID- 12048207
TI  - Insulin and sterol-regulatory element-binding protein-1c (SREBP-1C) regulation of
      gene expression in 3T3-L1 adipocytes. Identification of CCAAT/enhancer-binding
      protein beta as an SREBP-1C target.
AB  - We evaluated the hypothesis of sterol-regulatory element-binding protein (SREBP)
      1c being a general mediator of the transcriptional effects of insulin, with a
      focus on adipocytes, in which insulin profoundly influences specific gene
      expression. Using real time quantitative reverse transcriptase-PCR to monitor
      changes in the expression of about 50 genes that cover a wide range of adipocyte
      functions, we have compared the impact of insulin treatment with that of
      adenoviral overexpression of either dominant positive or dominant negative SREBP
      1c mutants in 3T3-L1 adipocytes. As expected, insulin up-regulated, dominant
      positive stimulated, and dominant negative decreased previously characterized
      direct SREBP targets (FAS, SCD-1, and low density lipoprotein receptor). We also
      identified three novel SREBP-1c transcriptional targets in adipocytes, which were
      confirmed by run-on assays: plasminogen activator inhibitor 1, CCAAT/enhancer
      binding protein delta (C/EBPdelta), and C/EBPbeta. Because most insulin-regulated
      genes were also modulated by SREBP-1c mutants, our data establish that 1) SREBP
      1c is an important mediator of insulin transcriptional effects in adipocytes, and
      2) C/EBPbeta is under the direct control of SREBP-1c, as demonstrated by the
      ability of SREBP-1c to activate the transcription from C/EBPbeta promoter through
      canonical SREBP binding sites. Thus, some of the effects of insulin and/or SREBP
      1c in mature fat cells might require C/EBPbeta or C/EBPdelta as transcriptional
      relays.

PMID- 12048208
TI  - Characterization of Drosophila hemoglobin. Evidence for hemoglobin-mediated
      respiration in insects.
AB  - In contrast to previous assumptions, the fruit fly Drosophila melanogaster
      possesses hemoglobin. This respiratory protein forms a monomer of about 17 kDa
      that is not exported into the hemolymph. Recombinant Drosophila hemoglobin
      displays a typical hexacoordinated deoxy spectrum and binds oxygen with an
      affinity of 0.12 torr. Four different hemoglobin transcripts have been
      identified, which are generated by two distinct promoters of the hemoglobin
      (glob1) gene but are identical in their coding regions. Putative binding sites
      for hypoxia-regulated transcription factors have been identified in the gene.
      Hemoglobin synthesis in Drosophila is mainly associated with the tracheal system
      and the fat body. This suggests that oxygen supply in insects may be more complex
      than thought previously and may depend on hemoglobin-mediated oxygen transport
      and storage in addition to simple diffusion.

PMID- 12048209
TI  - Vesicle-associated membrane protein-2/synaptobrevin binding to synaptotagmin I
      promotes O-glycosylation of synaptotagmin I.
AB  - Synaptotagmin I (Syt I), an evolutionarily conserved integral membrane protein of
      synaptic vesicles, is now known to regulate Ca2+-dependent neurotransmitter
      release. Syt I protein should undergo several post-translational modifications
      before maturation and subsequent functioning on synaptic vesicles (e.g. N
      glycosylation and fatty acylation in vertebrate Syt I), because the apparent
      molecular weight of Syt I on synaptic vesicles (mature form, 65,000) was much
      higher than the calculated molecular weight (47,400) predicted from the cDNA
      sequences both in vertebrates and invertebrates. Common post-translational
      modification(s) of Syt I conserved across phylogeny, however, have never been
      elucidated. In the present study, I discovered that dithreonine residues (Thr-15
      and Thr-16) at the intravesicular domain of mouse Syt I are post-translationally
      modified by a complex form of O-linked sugar (i.e. the addition of sialic acids)
      in PC12 cells and that the O-glycosylation of Syt I in COS-7 cells depends on the
      coexpression of vesicle-associated membrane protein-2 (VAMP-2)/synaptobrevin. I
      also showed that a transmembrane domain of Syt I directly interacts with isolated
      VAMP-2, but not VAMP-2, in the heterotrimeric SNARE (SNAP receptor) complex
      (vesicle SNARE, VAMP-2, and two target SNAREs, syntaxin IA and SNAP-25). Since di
      Thr or di-Ser residues are often found at the intravesicular domain of
      invertebrate Syt I, and VAMP-dependent O-glycosylation was also observed in squid
      Syt expressed in COS-7 cells, I propose that VAMP-dependent O-glycosylation of
      Syt I is a common modification during evolution and may have important role(s) in
      synaptic vesicle trafficking.

PMID- 12048210
TI  - Functional inactivation of the mouse nucleolar protein Bop1 inhibits multiple
      steps in pre-rRNA processing and blocks cell cycle progression.
AB  - Bop1 is a conserved nucleolar protein involved in rRNA processing and ribosome
      assembly in eukaryotes. Expression of its dominant-negative mutant Bop1 Delta in
      mouse cells blocks rRNA maturation and synthesis of large ribosomal subunits and
      induces a reversible, p53-dependent cell cycle arrest. In this study, we have
      conducted a deletion analysis of Bop1 and identified a new mutant, Bop1N2, that
      also acts as a potent inhibitor of cell cycle progression. Bop1N2 and Bop1 Delta
      are C-terminal and N-terminal deletion mutants, respectively, and share only 72
      amino acid residues. Both mutant proteins are localized to the nucleolus and
      strongly inhibit rRNA processing, suggesting that activation of a cell cycle
      checkpoint by Bop1 mutants is linked to their inhibitory effects on rRNA and
      ribosome synthesis. By using these dominant-negative mutants as well as antisense
      oligonucleotides to interfere with endogenous Bop1, we identified specific rRNA
      processing steps that require Bop1 function in mammalian cells. Our data
      demonstrate that Bop1 is required for proper processing at four distinct sites
      located within the internal transcribed spacers ITS1 and ITS2 and the 3' external
      spacer. We propose a model in which Bop1 serves as an essential factor in
      ribosome formation that coordinates processing of the spacer regions in pre-rRNA.

PMID- 12048211
TI  - Role of MAP kinases in the 1,25-dihydroxyvitamin D3-induced transactivation of
      the rat cytochrome P450C24 (CYP24) promoter. Specific functions for ERK1/ERK2 and
      ERK5.
AB  - The current study investigated the action of 1,25-dihydroxyvitamin D(3) (1,25D)
      at the genomic and signal transduction levels to induce rat cytochrome P450C24
      (CYP24) gene expression. A rat CYP24 promoter containing two vitamin D response
      elements and an Ets-1 binding site was used to characterize the mechanism of
      actions for the 1,25D secosteroid hormone. The Ets-1 binding site was determined
      to function cooperatively with the most proximal vitamin D response element in a
      hormone-dependent fashion. Evidence was obtained for distinct roles of ERK1/ERK2
      and ERK5 in the 1,25D-inductive actions. Specifically, 1,25D stimulated the
      activities of ERK1/ERK2 and ERK5 in a Ras-dependent manner. Promoter induction
      was inhibited by mitogen-activated protein (MAP) kinase inhibitors (PD98059 and
      U0126) and a dominant-negative Ras mutant (Ras17N). Induction of CYP24 by 1,25D
      was also inhibited by overexpression of dominant-negative mutants of ERK1 and
      MEK5 (ERK1K71R and MEK5(A)). The p38 and JNK MAP kinases were not required for
      the action of 1,25D. 9-cis retinoid X receptor alpha (RXR alpha) interacted with
      ERK2 but not ERK5 in intact cells, whereas Ets-1 interacted preferentially with
      ERK5. Increased phosphorylation of RXR alpha and Ets-1 was detected in response
      to 1,25D. Activated ERK2 and ERK5 specifically phosphorylated RXR alpha and Ets
      1, respectively. Mutagenesis of Ets-1 (T38A) reduced CYP24 promoter activity to
      levels observed with the dominant-negative MEK5(A) and inhibited ERK5-directed
      phosphorylation. Mutated RXR alpha (S260A) inhibited 1,25D-induced CYP24 promoter
      activity and abolished phosphorylation by activated ERK2. The 1,25D-inductive
      action through ERK5 involved Ets-1 phosphorylation at threonine 38, whereas
      hormone stimulation of ERK1/ERK2 required RXR alpha phosphorylation on serine
      260. The ERK1/ERK2 and ERK5 modules provide a novel mechanism for linking the
      rapid signal transduction and slower transcription actions of 1,25D to induce
      CYP24 gene expression.

PMID- 12048212
TI  - Ameliorated hepatic insulin resistance is associated with normalization of
      microsomal triglyceride transfer protein expression and reduction in very low
      density lipoprotein assembly and secretion in the fructose-fed hamster.
AB  - To determine whether reduction of insulin resistance could ameliorate fructose
      induced very low density lipoprotein (VLDL) oversecretion and to explore the
      mechanism of this effect, fructose-fed hamsters received placebo or rosiglitazone
      for 3 weeks. Rosiglitazone treatment led to normalization of the blunted insulin
      mediated suppression of the glucose production rate and to a approximately 2-fold
      increase in whole body insulin-mediated glucose disappearance rate (p < 0.001).
      Rosiglitazone ameliorated the defect in hepatocyte insulin-stimulated tyrosine
      phosphorylation of the insulin receptor, IRS-1, and IRS-2 and the reduced protein
      mass of IRS-1 and IRS-2 induced by fructose feeding. Protein-tyrosine phosphatase
      1B levels were increased with fructose feeding and were markedly reduced by
      rosiglitazone. Rosiglitazone treatment led to a approximately 50% reduction of
      VLDL secretion rates (p < 0.05) in vivo and ex vivo. VLDL clearance assessed
      directly in vivo was not significantly different in the FR (fructose-fed +
      rosiglitazone-treated) versus F (fructose-fed + placebo-treated) hamsters,
      although there was a trend toward a lower clearance with rosiglitazone. Enhanced
      stability of nascent apolipoprotein B (apoB) in fructose-fed hepatocytes was
      evident, and rosiglitazone treatment resulted in a significant reduction in apoB
      stability. The increase in intracellular mass of microsomal triglyceride transfer
      protein seen with fructose feeding was reduced by treatment with rosiglitazone.
      In conclusion, improvement of hepatic insulin signaling with rosiglitazone, a
      peroxisome proliferator-activated receptor gamma agonist, is associated with
      reduced hepatic VLDL assembly and secretion due to reduced intracellular apoB
      stability.

PMID- 12048213
TI  - A novel strategy to engineer functional fluorescent inhibitory G-protein alpha
      subunits.
AB  - Signaling studies in living cells would be greatly facilitated by the development
      of functional fluorescently tagged G-protein alpha subunits. We have designed
      G(i/o)alpha subunits fused to the cyan fluorescent protein and assayed their
      function by studying the following two signal transduction pathways: the
      regulation of G-protein-gated inwardly rectifying K(+) channels (Kir3.0 family)
      and adenylate cyclase. Palmitoylation and myristoylation consensus sites were
      removed from G(i/o) alpha subunits (G(i1)alpha, G(i2)alpha, G(i3)alpha, and
      G(oA)alpha) and a mutation introduced at Cys(-4) rendering the subunit resistant
      to pertussis toxin. This construct was fused in-frame with cyan fluorescent
      protein containing a short peptide motif from GAP43 that directs palmitoylation
      and thus membrane targeting. Western blotting confirmed G(i/o)alpha protein
      expression. Confocal microscopy and biochemical fractionation studies revealed
      membrane localization. Each mutant G(i/o) alpha subunit significantly reduced
      basal current density when transiently expressed in a stable cell line expressing
      Kir3.1 and Kir3.2A, consistent with the sequestration of the Gbetagamma dimer by
      the mutant Galpha subunit. Moreover, each subunit was able to support A1-mediated
      and D2S-mediated channel activation when transiently expressed in pertussis toxin
      treated cells. Overexpression of tagged G(i3)alpha and G(oA)alpha alpha subunits
      reduced receptor-mediated and forskolin-induced cAMP mobilization.

PMID- 12048215
TI  - Beta-adrenergic receptor-mediated DNA synthesis in cardiac fibroblasts is
      dependent on transactivation of the epidermal growth factor receptor and
      subsequent activation of extracellular signal-regulated kinases.
AB  - Cardiac hypertrophy often leads to heart failure and is associated with abnormal
      myocardial adrenergic signaling. This enlargement of myocardial mass can involve
      not only an increase in cardiomyocyte size, but increased proliferation of
      cardiac fibroblasts. A potential key player in the cardiac hypertrophic response
      is the ERK family of MAPKs. To gain mechanistic insight into adrenergic
      regulation of myocardial mitogenic signaling, we examined beta-adrenergic
      receptor (beta-AR) stimulation of ERK activation and DNA synthesis in cultured
      adult rat cardiac fibroblasts, including the involvement of tyrosine kinases in
      this signaling pathway. Addition of the beta-AR agonist isoproterenol (ISO) to
      serum-starved cells induced DNA synthesis in a dose-dependent manner, and this
      was inhibited by selective inhibitors of the epidermal growth factor receptor
      (EGFR). Importantly and in agreement with the involvement of MAPKs and the EGFR
      in this response in cardiac fibroblasts, the EGFR inhibitor AG1478 attenuated ISO
      induced ERK phosphorylation. Moreover, pretreatment with PP2, a selective
      inhibitor of the Src tyrosine kinase, attenuated both ISO-mediated EGFR
      phosphorylation and ERK activation. Furthermore, studies in these cardiac
      fibroblasts showed that phosphatidylinositol 3-kinase contributed to beta-AR
      mediated ERK activation, but not to EGFR activation. Finally, studies using
      selective inhibitors of matrix metalloproteases indicated that they and heparin
      bound EGF shedding were involved in beta-AR-induced ERK activation and subsequent
      DNA synthesis in cardiac fibroblasts. Because these cells primarily express the
      beta(2)-AR subtype, our findings indicate that beta(2)-AR-mediated EGFR
      transactivation of intracellular tyrosine kinase signaling pathways is the major
      signaling pathway responsible for the adrenergic stimulation of mitogenesis of
      cardiac fibroblasts.

PMID- 12048216
TI  - The Escherichia coli cytochrome c maturation (Ccm) system does not detectably
      attach heme to single cysteine variants of an apocytochrome c.
AB  - Cytochromes c are typically characterized by the covalent attachment of heme to
      polypeptide through two thioether bonds with the cysteine residues of a Cys-Xaa
      Xaa-Cys-His peptide motif. In many Gram-negative bacteria, the heme is attached
      to the polypeptide by the periplasmically functioning cytochrome c maturation
      (Ccm) proteins. Exceptionally, Hydrogenobacter thermophilus cytochrome c(552),
      which has a normal CXXCH heme-binding motif, and variants with AXXCH, CXXAH, and
      AXXAH motifs, can be expressed as stable holocytochromes in the cytoplasm of
      Escherichia coli. By targeting these proteins to the periplasm using a signal
      peptide, with or without co-expression of the Ccm proteins, we have assessed the
      ability of the Ccm system to attach heme to proteins with no, one, or two
      cysteine residues in the heme-binding motif. Only the wild-type protein, with two
      cysteines, was effectively processed and thus accumulated in the periplasm as a
      holocytochrome. This is strong evidence for disulfide bond formation involving
      the two cysteine residues of apocytochrome c as an intermediate in Ccm-type Gram
      negative bacterial cytochrome c biogenesis and/or that only a pair of cysteines
      can be recognized by the heme attachment apparatus.

PMID- 12048214
TI  - Cooperative binding of the cytoplasm to vacuole targeting pathway proteins, Cvt13
      and Cvt20, to phosphatidylinositol 3-phosphate at the pre-autophagosomal
      structure is required for selective autophagy.
AB  - Autophagy is a catabolic membrane-trafficking mechanism involved in cell
      maintenance and development. Most components of autophagy also function in the
      cytoplasm to vacuole targeting (Cvt) pathway, a constitutive biosynthetic pathway
      required for the transport of aminopeptidase I (Ape1). The protein components of
      autophagy and the Cvt pathway include a putative complex composed of Apg1 kinase
      and several interacting proteins that are specific for either the Cvt pathway or
      autophagy. A second required complex includes a phosphatidylinositol (PtdIns) 3
      kinase and associated proteins that are involved in its activation and
      localization. The majority of proteins required for the Cvt and autophagy
      pathways localize to a perivacuolar pre-autophagosomal structure. We show that
      the Cvt13 and Cvt20 proteins are required for transport of precursor Ape1 through
      the Cvt pathway. Both proteins contain phox homology domains that bind PtdIns(3)P
      and are necessary for membrane localization to the pre-autophagosomal structure.
      Functional phox homology domains are required for Cvt pathway function. Cvt13 and
      Cvt20 interact with each other and with an autophagy-specific protein, Apg17,
      that interacts with Apg1 kinase. These results provide the first functional
      connection between the Apg1 and PtdIns 3-kinase complexes. The data suggest a
      role for PtdIns(3)P in the Cvt pathway and demonstrate that this lipid is
      required at the pre-autophagosomal structure.

PMID- 12048217
TI  - p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase
      in glial cells. Roles of nuclear factors, nuclear factor kappa B, cAMP response
      element-binding protein, CCAAT/enhancer-binding protein-beta, and activating
      transcription factor-2.
AB  - Previous studies have shown that mitogen-activated protein kinase (MAPK) cascades
      signal the induction of inducible nitric-oxide synthase (iNOS) in glial cells
      (Bhat, N. R., Zhang, P., Lee, J. C., and Hogan E. L. (1998) J. Neurosci. 18, 1633
      1641; Bhat, N. R., Zhang, P., and Bhat, A. N. (1999) J. Neurochem. 72, 472-478).
      This study further investigates the role of p38 MAPK in the transcriptional
      activation of the iNOS gene by transient transfection with constitutively active
      upstream kinases in the pathway (i.e. MAPK kinase 3 (MKK3b(E)) and MAPK kinase 6
      (MKK6b(E)). Expression in C-6 glial cells of either MKK3b(E) or MKK6b(E) resulted
      in an induction of the activity of a cotransfected rat iNOS promoter-reporter
      (iNOS-luciferase (Luc)) gene and an enhancement of cytokine-induced expression of
      iNOS mRNA, both of which were inhibitable by the p38 MAPK inhibitor SB203580. The
      MKK constructs also induced cAMP response element-mediated (CRE-Luc) and nuclear
      factor kappa B-dependent (nuclear factor kappa B-Luc) transcriptional activities.
      Transfection with dominant negative (dn) forms of CRE-binding protein (CREB) and
      CCAAT/enhancer-binding protein (C/EBP), the two CRE-binding transcription factors
      targeted by the p38 MAPK pathway, resulted in opposite effects; dnCREB enhanced
      and dnC/EBP inhibited iNOS-Luc parallel to their effects on CRE-Luc. In addition,
      the induction, by MKK3b(E) and MKK6b(E), of iNOS promoter activity was enhanced
      by a wild-type activating transcription factor (ATF-2), whereas a phosphorylation
      defective form of ATF-2 had a suppressive effect. The results of these molecular
      studies provide evidence for an important role for the p38 MAPK pathway in the
      transcriptional activation of the iNOS gene in rat glial cells involving the
      transcription factors nuclear factor kappa B, C/EBP, and ATF-2.

PMID- 12048218
TI  - Muscle expression of human retinol-binding protein (RBP). Suppression of the
      visual defect of RBP knockout mice.
AB  - Mice lacking retinol-binding protein (RBP) have low circulating retinol levels.
      They have severe visual defects due to a low content of retinol or retinyl esters
      in the eye. A transgenic mouse strain that expresses human RBP under the control
      of the muscle creatine kinase promoter in the null background was generated. The
      exogenous protein bound retinol and transthyretin in the circulation and
      effectively delivered retinol to the eye. Thus, RBP expressed from an ectopic
      source suppresses the visual phenotype, and retinoids accumulate in the eye. No
      human RBP was found in the retinal pigment epithelium of the transgenic mice,
      indicating that retinol uptake by the eye does not entail endocytosis of the
      carrier RBP.

PMID- 12048219
TI  - p38 kinase-dependent and -independent Inhibition of protein kinase C zeta and 
      alpha regulates nitric oxide-induced apoptosis and dedifferentiation of articular
      chondrocytes.
AB  - In articular chondrocytes, nitric oxide (NO) production triggers
      dedifferentiation and apoptotic cell death that is regulated by the converse
      functions of two mitogen-activated protein kinase subtypes, extracellular signal
      regulated kinase (ERK) and p38 kinase. Since protein kinase C (PKC) transduces
      signals that influence differentiation, survival, and apoptosis of various cell
      types, we investigated the roles and underlying molecular mechanisms of action of
      PKC isoforms in NO-induced dedifferentiation and apoptosis of articular
      chondrocytes. We report here that among the expressed isoforms, activities of
      PKCalpha and -zeta were reduced during NO-induced dedifferentiation and
      apoptosis. Inhibition of PKCalpha activity was independent of NO-induced
      activation of ERK or p38 kinase and occurred due to blockage of expression. On
      the other hand, PKCzeta activity was inhibited as a result of NO-induced p38
      kinase activation and was observed prior to proteolytic cleavage by a caspase
      mediated process to generate enzymatically inactive fragments. Inhibition of
      PKCalpha or -zeta activities potentiated NO-induced apoptosis, whereas ectopic
      expression of these isoforms significantly reduced the number of apoptotic cells
      and blocked dedifferentiation. Ectopic expression of PKCalpha or -zeta did not
      affect p38 kinase or ERK but inhibited the p53 accumulation and caspase-3
      activation that are required for NO-induced apoptosis of chondrocytes. Therefore,
      our results collectively indicate that p38 kinase-independent and -dependent
      inhibition of PKCalpha and -zeta, respectively, regulates NO-induced apoptosis
      and dedifferentiation of articular chondrocytes.

PMID- 12048220
TI  - Sphingolipid metabolism and signaling minireview series.

PMID- 12048221
TI  - Late-life engagement in social and leisure activities is associated with a
      decreased risk of dementia: a longitudinal study from the Kungsholmen project.
AB  - Recent findings suggest that a rich social network may decrease the risk of
      developing dementia. The authors hypothesized that such a protective effect may
      be due to social interaction and intellectual stimulation. To test this
      hypothesis, data from the 1987-1996 Kungsholmen Project, a longitudinal
      population-based study carried out in a central area of Stockholm, Sweden, were
      used to examine whether engagement in different activities 6.4 years before
      dementia diagnosis was related to a decreased incidence of dementia. Dementia
      cases were diagnosed by specialists according to Diagnostic and Statistical
      Manual of Mental Disorders, Third Edition, Revised, criteria. After adjustment
      for age, sex, education, cognitive functioning, comorbidity, depressive symptoms,
      and physical functioning at the first examination, frequent (daily-weekly)
      engagement in mental, social, or productive activities was inversely related to
      dementia incidence. Adjusted relative risks for mental, social, and productive
      activities were 0.54 (95% confidence interval (CI): 0.34, 0.87), 0.58 (95% CI:
      0.37, 0.91), and 0.58 (95% CI: 0.38, 0.91), respectively. Similar results were
      found when these three factors were analyzed together in the same model. Results
      suggest that stimulating activity, either mentally or socially oriented, may
      protect against dementia, indicating that both social interaction and
      intellectual stimulation may be relevant to preserving mental functioning in the
      elderly.

PMID- 12048222
TI  - Depression and cancer risk: a register-based study of patients hospitalized with
      affective disorders, Denmark, 1969-1993.
AB  - The authors investigated the cancer risk of patients hospitalized for depression
      in a nationwide Danish cohort study. All 89,491 adults in Denmark who had been
      admitted to a hospital with depression, as defined in the International
      Classification of Diseases, Eighth Revision, between 1969 and 1993 were
      identified. There were 1,117,006 person-years of follow-up. Incidence rates of
      all cancers and of site-specific cancers were compared with national incidence
      rates for first primary cancers, with data being adjusted for sex, age, and
      calendar time. A total of 9,922 cases of cancer were diagnosed in the cohort,
      with 9,434.6 having been expected; this yielded a standardized incidence ratio of
      1.05 (95% confidence interval (CI): 1.03, 1.07). The risk of cancer was increased
      for the first year after hospital admission, with brain cancer especially
      occurring more frequently than expected. When the first year of follow-up was
      excluded, the increase was attributable mainly to an increased risk of tobacco
      related cancers: Standardized incidence ratios for non-tobacco-related cancers
      were 1.00 (95% CI: 0.97, 1.03) after 1-9 years of follow-up and 0.99 (95% CI:
      0.95, 1.02) after 10 or more years of follow-up. These data provide no support
      for the hypothesis that depression independently increases risk of cancer, but
      they emphasize the deleterious effect that depression can have on lifestyle
      factors.

PMID- 12048223
TI  - Adult and childhood leukemia near a high-power radio station in Rome, Italy.
AB  - Some recent epidemiologic studies suggest an association between lymphatic and
      hematopoietic cancers and residential exposure to high-frequency electromagnetic
      fields (100 kHz to 300 GHz) generated by radio and television transmitters.
      Vatican Radio is a very powerful station located in a northern suburb of Rome,
      Italy. In the 10-km area around the station, with 49,656 residents (in 1991),
      leukemia mortality among adults (aged >14 years; 40 cases) in 1987-1998 and
      childhood leukemia incidence (eight cases) in 1987-1999 were evaluated. The risk
      of childhood leukemia was higher than expected for the distance up to 6 km from
      the radio station (standardized incidence rate = 2.2, 95% confidence interval:
      1.0, 4.1), and there was a significant decline in risk with increasing distance
      both for male mortality (p = 0.03) and for childhood leukemia (p = 0.036). The
      study has limitations because of the small number of cases and the lack of
      exposure data. Although the study adds evidence of an excess of leukemia in a
      population living near high-power radio transmitters, no causal implication can
      be drawn. There is still insufficient scientific knowledge, and new epidemiologic
      studies are needed to clarify a possible leukemogenic effect of residential
      exposure to radio frequency radiation.

PMID- 12048224
TI  - Fruits, vegetables, and adenomatous polyps: the Minnesota Cancer Prevention
      Research Unit case-control study.
AB  - Although high vegetable intakes have been associated with a lower risk of
      colorectal cancer, this relation is less well established for the precursor
      lesions, adenomatous polyps. With a case-control design involving adenomatous
      polyp cases (n = 564), colonoscopy-negative controls who were polyp free at
      colonoscopy (n = 682), and community controls (n = 535), this 1991-1994 Minnesota
      Cancer Prevention Research Unit study investigated the relation between fruit and
      vegetable consumption and first incident adenomatous polyps. Dietary intake was
      assessed using a food frequency questionnaire. For women, adenoma risk was
      approximately halved in the highest versus lowest quintile of juice consumption
      (cases vs. colonoscopy-negative controls: odds ratio (OR) = 0.50, 95% confidence
      interval (CI): 0.27, 0.92; cases vs. community controls: OR = 0.56, 95% CI: 0.30,
      1.06). The association was stronger for adenomas with moderate or severe
      dysplasia compared with mild dysplasia. Juice was not associated with adenoma
      risk in men. The results for fruits, vegetables, total fruits and vegetables,
      green leafy vegetables, and several botanically and phytochemically defined
      subgroups generally were not statistically significant. Because elevated
      vegetable consumption has been associated with a lower risk of colorectal cancer,
      vegetables may have a stronger role in preventing the progression of adenomas to
      carcinomas rather than in preventing the initial appearance of adenomas.

PMID- 12048225
TI  - Gender- and race-specific determination of albumin excretion rate using albumin
      to-creatinine ratio in single, untimed urine specimens: the Coronary Artery Risk
      Development in Young Adults Study.
AB  - Although albumin excretion rate is commonly estimated by using albumin/creatinine
      ratio (A/C), gender and race differences in creatinine excretion may bias this
      estimate. The authors optimize the use of an untimed (spot) urine specimen among
      3,371 Blacks and Whites aged 28-40 years in the Coronary Artery Risk Development
      in Young Adults Study in 1995-1996. Using three 24-hour collections during the
      year 5 examination, they determined k = 0.68 x 0.88 in Black men, 0.88 in Black
      women, 0.68 in White men, and 1.0 in White women to reflect gender and race
      differences in creatinine excretion. The authors then computed A/C adjusted for
      race and sex differences in creatinine excretion (A/kC) by using an untimed urine
      sample in the year 10 examination. A/kC >or= 25 mg/g (194 cases of
      microalbuminuria and 26 cases of clinical grade albuminuria) was more common
      among Blacks (9.1%) than among Whites (4.2%) and among men (8.2%) than among
      women (5.0%). Use of the unadjusted A/C underestimated the prevalence of
      microalbuminuria among men by 52% and among Blacks by 26%. Adjustment of A/C
      permitted more accurate estimation of albumin excretion rate. Men and Blacks have
      a higher albumin excretion rate than do women and Whites and may thereby have an
      increased risk of microvascular and macrovascular disease.

PMID- 12048226
TI  - Lyme disease incidence in Wisconsin: a comparison of state-reported rates and
      rates from a population-based cohort.
AB  - Few studies have assessed the accuracy and completeness of Lyme disease
      surveillance systems. Lyme disease cases were identified through review of
      medical records for residents of the Marshfield Epidemiologic Study Area (MESA),
      a population-based cohort of nearly 80,000 in north-central Wisconsin for which
      comprehensive medical care data are available through the Marshfield Clinic.
      These cases were compared with cases reported to the Wisconsin Division of Public
      Health to estimate the completeness of reporting. Annual incidence rates were
      calculated for MESA using the cases identified from chart review. Division of
      Public Health data were used to calculate statewide reported incidence rates, as
      well as rates for an eight-county region that surrounds and includes the MESA
      region. Of Lyme disease cases meeting the national case definition identified in
      MESA, 34% were reported to the state. The average incidence of Lyme disease (1992
      1998) was 19.1 per 100,000 per year in MESA, 17.0 in the surrounding eight-county
      region, and 9.0 statewide. Trends in reported incidence across time, gender, and
      age in the surrounding eight-county region were generally comparable with those
      observed in MESA. These findings suggest that the passive surveillance system
      monitored trends in Lyme disease incidence reasonably well despite underreporting
      of cases.

PMID- 12048227
TI  - How good are parents at assessing melanocytic nevi on their children? A study
      comparing parental counts, dermatologist counts, and counts obtained from
      photographs.
AB  - The objective of this study was to evaluate agreement among counts of melanocytic
      nevi made by parents, counts made by a dermatologist, and counts made by
      assessment of photographs. In 1990, 421 schoolchildren aged 6-15 years from
      Townsville, Queensland, Australia (latitude 19.16 degrees S), participated in the
      Eastern Australian Childhood Nevus Study. In an agreement study, parents were
      asked to mark on an anatomic diagram any melanocytic nevi greater than or equal
      to 2 mm in diameter and greater than or equal to 5 mm in diameter they observed
      on their child's back prior to the child's examination by a dermatologist; 324
      parents responded (a 77% response rate). Standardized slide photographs of each
      child's back were taken, and melanocytic nevi were counted by an experienced non
      medical-examiner upon projection. Agreement was assessed graphically and with the
      concordance correlation coefficient (r(c)). Parental counts of melanocytic nevi
      were similar to counts made by the dermatologist (n = 77; for nevi >or=2 mm, r(c)
      = 0.51; for nevi >or=5 mm, r(c) = 0.78) and counts obtained from the photographs
      (n = 324; for nevi >or=2 mm, r(c) = 0.68; for nevi >or=5 mm, r(c) = 0.68). Few
      parents reported false-positive lesions. Parents tended to underestimate the
      number of melanocytic nevi greater than or equal to 2 mm in diameter (mean
      difference from dermatologist: -3.2, standard deviation 6.8; mean difference from
      photographs: -1.1, standard deviation 5.1), particularly when the density of
      melanocytic nevi was high. Agreement between dermatologist counts and photograph
      counts was high (for nevi >or=2 mm, r(c) = 0.80; for nevi >or=5 mm, r(c) = 0.87).
      The authors conclude that parents are capable of counting melanocytic nevi on
      their children's skin with some validity. In epidemiologic studies of children,
      counts of melanocytic nevi obtained from standardized photographs have the
      potential to replace counts made by physicians.

PMID- 12048228
TI  - Racial misclassification of American Indians in Oklahoma State surveillance data
      for sexually transmitted diseases.
AB  - The burden of sexually transmitted diseases (STDs) is high in American
      Indian/Alaska Native (AI/AN) populations. In addition, race is often
      misclassified in surveillance data. This study examined potential racial
      misclassification of American Indians in STD surveillance data in Oklahoma.
      Oklahoma State STD surveillance data for 1995 were matched with the Oklahoma
      State Indian Health Service Patient Registry to determine the number of AI/AN
      women who had one of three STDs but were not listed in Oklahoma surveillance data
      as AI/AN. Accounting for racial misclassification increased the rate of chlamydia
      for AI/AN women in Oklahoma by 32% (342/100,000 vs. 452/100,000) in the overall
      population. For gonorrhea, the rate increased by 57% (94/100,000 vs. 148/100,000)
      and for syphilis by 27% (15/100,000 vs. 19/100,000). Misclassified AI/AN women
      most often were classified as "White," and the likelihood of misclassification
      increased with a lower percentage of AI/AN ancestry. These findings indicate that
      STD rates may be underestimated for AI/AN populations nationwide. Racial
      misclassification in state surveillance data causes inaccuracies in
      characterizing the burden of infectious diseases in minorities.

PMID- 12048229
TI  - Re: "The river: a journey to the source of HIV and AIDS".

PMID- 12048230
TI  - Re: "Tracking of cardiovascular risk factors: the Tromso Study, 1979, 1995".

PMID- 12048231
TI  - Ligand binding and protein dynamics in neuroglobin.
AB  - Neuroglobin (Ngb) is a recently discovered protein in vertebrate brain tissue
      that belongs to the globin family of proteins. It has been implicated in the
      neuronal response to hypoxia or ischemia, although its physiological role has
      been hitherto unknown. Ngb is hexacoordinate in the ferrous deoxy form under
      physiological conditions. To bind exogenous ligands like O(2) and CO, the His E7
      endogenous ligand is displaced from the sixth coordination. By using infrared
      spectroscopy and nanosecond time-resolved visible spectroscopy, we have
      investigated the ligand-binding reaction over a wide temperature range (3-353 K).
      Multiple, intrinsically heterogeneous distal heme pocket conformations exist in
      NgbCO. Photolysis at cryogenic temperatures creates a five-coordinate deoxy
      species with very low geminate-rebinding barriers. The photodissociated CO is
      observed to migrate within the distal heme pocket even at 20 K. Flash photolysis
      near physiological temperature (275-353 K) exhibits four sequential kinetic
      features: (i) geminate rebinding (t < 1 micros); (ii) extremely fast bimolecular
      exogenous ligand binding (10 micros < t < 1 ms) with a nontrivial temperature
      dependence; (iii) endogenous ligand binding (100 micros < t < 10 ms), which can
      be studied by using flash photolysis on deoxy Ngb; and (iv) displacement of the
      endogenous by the exogenous ligand (10 ms < t < 10 ks). All four processes are
      markedly nonexponential, suggesting that Ngb fluctuates among different
      conformations on surprisingly long time scales.

PMID- 12048232
TI  - Quantitative prediction of NF-kappa B DNA-protein interactions.
AB  - We describe a general method based on principal coordinates analysis to predict
      the effects of single-nucleotide polymorphisms within regulatory sequences on DNA
      protein interactions. We use binding data for the transcription factor NF-kappaB
      as a test system. The method incorporates the effects of interactions between
      base pair positions in the binding site, and we demonstrate that such
      interactions are present for NF-kappaB. Prediction accuracy is higher than with
      profile models, confirmed by crossvalidation and by the experimental verification
      of our predictions for additional sequences. The binding affinities of all
      potential NF-kappaB sites on human chromosome 22, together with the effects of
      known single-nucleotide polymorphisms, are calculated to determine likely
      functional variants. We propose that this approach may be valuable, either on its
      own or in combination with other methods, when standard profile models are
      disadvantaged by complex internucleotide interactions.

PMID- 12048233
TI  - Localized expression of a dpp/BMP2/4 ortholog in a coral embryo.
AB  - As the closest outgroup to the Bilateria, the Phylum Cnidaria is likely to be
      critical to understanding the origins and evolution of body axes. Proteins of the
      decapentaplegic (DPP)/bone morphogenetic protein (BMP) 2/4 subfamily are central
      to the specification of the dorsoventral (D/V) axis in bilateral animals, albeit
      with an axis inversion between arthropods and chordates. We show that a
      dpp/BMP2/4 ortholog (bmp2/4-Am) is present in the reef-building scleractinian
      coral, Acropora millepora (Class Anthozoa) and that it is capable of causing
      phenotypic effects in Drosophila that mimic those of the endogenous dpp gene. We
      also show that, during coral embryonic development, bmp2/4-Am expression is
      localized in an ectodermal region adjacent to the blastopore. Thus, a
      representative of the DPP/BMP2/4 subfamily of ligands was present in the common
      ancestor of diploblastic and triploblastic animals where it was probably
      expressed in a localized fashion during development. A localized source of
      DPP/BMP2/4 may have already been used in axis formation in this ancestor, or it
      may have provided a means by which an axis could evolve in triploblastic animals.

PMID- 12048234
TI  - Minimal principle for rotor filaments.
AB  - Three-dimensional rotors, or scroll waves, provide essential insight into the
      activity of excitable media. They also are a suspected cause in the formation and
      maintenance of ventricular fibrillation, whose lethality is well known. It is
      therefore of considerable interest to find out what configurations can be adopted
      by such pathologies. A scroll's behavior is embodied in its organizing center or
      filament, a largely quiescent tube about which the scroll rotates. Predicting
      filament shape has normally required computer-intensive simulations of the whole
      scroll in time. We have found a fast and robust principle that yields the
      prediction for stationary filaments on a purely geometrical basis, blind to the
      reaction parameters of the medium. The procedure is to calculate the filament
      shape as a minimal path. We work in singly diffusive media whose diffusivity
      tensor--and no other feature--varies spatially. Mathematical and numerical
      evidence is presented for the proposition that a stable filament is a geodesic in
      a three-dimensional space whose metric is given by the inverse diffusivity tensor
      of the medium. Away from the boundaries, a stable filament is unaffected by the
      reaction parameters. The algorithmic aspects of this work are subsidiary to our
      main purpose of drawing attention to the universal and unexpectedly exact fit of
      an elementary geodesic principle within reaction-diffusion theories.

PMID- 12048235
TI  - Constitutive activation of Stat5a by retrovirus integration in early pre-B
      lymphomas of SL/Kh strain mice.
AB  - We found that the second intron of Stat5a was one of the common integration sites
      of the endogenous ecotropic murine leukemia virus, i.e., SL/Kh virus integration
      1 (Svi1), in early pre-B lymphomas in SL/Kh mice. The high expression of STAT5A
      induced by Svi1 integration and activation accelerated the transcription of its
      target genes such as c-Myc. Transfection of the constitutively active Stat5a
      mutant cDNA, but not of the wild-type cDNA, to the bone marrow cells induced
      colony formation of pre-B cells in a methylcellulose medium and escaped from
      dependence on IL-7. Such growth depended on a genetic factor in the SL/Kh strain.
      Consitutively high expression of Stat5a either by retrovirus integration or
      transfection of active mutant cDNA can be lymphomagenic to early pre-B cells in
      collaboration with a certain genetic background factor of mice.

PMID- 12048236
TI  - Chromosome translocations and covert leukemic clones are generated during normal
      fetal development.
AB  - Studies on monozygotic twins with concordant leukemia and retrospective scrutiny
      of neonatal blood spots of patients with leukemia indicate that chromosomal
      translocations characteristic of pediatric leukemia often arise prenatally,
      probably as initiating events. The modest concordance rate for leukemia in
      identical twins ( approximately 5%), protracted latency, and transgenic modeling
      all suggest that additional postnatal exposure and/or genetic events are required
      for clinically overt leukemia development. This notion leads to the prediction
      that chromosome translocations, functional fusion genes, and preleukemic clones
      should be present in the blood of healthy newborns at a rate that is
      significantly greater than the cumulative risk of the corresponding leukemia.
      Using parallel reverse transcriptase-PCR and real-time PCR (Taqman) screening, we
      find that the common leukemia fusion genes, TEL-AML1 or AML1-ETO, are present in
      cord bloods at a frequency that is 100-fold greater than the risk of the
      corresponding leukemia. Single-cell analysis by cell enrichment and
      immunophenotype/fluorescence in situ hybridization multicolor staining confirmed
      the presence of translocations in restricted cell types corresponding to the B
      lymphoid or myeloid lineage of the leukemias that normally harbor these fusion
      genes. The frequency of positive cells (10(-4) to 10(-3)) indicates substantial
      clonal expansion of a progenitor population. These data have significant
      implications for the pathogenesis, natural history, and etiology of childhood
      leukemia.

PMID- 12048237
TI  - Adhesion induced by mobile binders: dynamics.
AB  - We consider a vesicle bilayer loaded with molecules that can bind (upon contact)
      with a solid surface, following the classical model of Bell, Dembo, and Bongrand.
      We are interested in situations where the contact area varies with time: we
      assume that binders can then migrate via diffusion. The resulting dissipation and
      lag create a retarded force on the contact line, which could be significant in
      squeezing or rolling experiments. However, there are two cases where we expect
      the lag force to be ineffective: (i) separation by shrinking of an adhesive patch
      (where the Evans "tear out" process turns out to be less costly) and (ii)
      spontaneous growth of a patch from a point contact. In this last case, the lag
      force is weak, and we give detailed predictions for the growth laws.

PMID- 12048238
TI  - Neuronal loss and brain atrophy in mice lacking cathepsins B and L.
AB  - Cathepsins B and L are widely expressed cysteine proteases implicated in both
      intracellular proteolysis and extracellular matrix remodeling. However, specific
      roles remain to be validated in vivo. Here we show that combined deficiency of
      cathepsins B and L in mice is lethal during the second to fourth week of life.
      Cathepsin B(-/-)/L(-/-) mice reveal a degree of brain atrophy not previously seen
      in mice. This is because of massive apoptosis of select neurons in the cerebral
      cortex and the cerebellar Purkinje and granule cell layers. Neurodegeneration is
      accompanied by pronounced reactive astrocytosis and is preceded by an
      accumulation of ultrastructurally and biochemically unique lysosomal bodies in
      large cortical neurons and by axonal enlargements. Our data demonstrate a pivotal
      role for cathepsins B and L in maintenance of the central nervous system.

PMID- 12048239
TI  - Presenilin-1 mutations of leucine 166 equally affect the generation of the Notch
      and APP intracellular domains independent of their effect on Abeta 42 production.
AB  - The Alzheimer's disease (AD)-associated presenilin (PS) proteins are required for
      the gamma-secretase cleavages of the beta-amyloid precursor protein and the site
      3 (S3) protease cleavage of Notch. These intramembrane cleavages release amyloid
      beta peptide (Abeta), including the pathogenic 42-aa variant (Abeta(42)), as well
      as the beta-amyloid precursor protein and the Notch intracellular domains (AICD,
      NICD). Whereas Abeta is generated by endoproteolysis in the middle of the
      transmembrane domain, AICD and NICD are generated by cleavages at analogous
      positions close to the cytoplasmic border of the transmembrane domain. Numerous
      mutations causing familial AD (FAD) that all cause increased production of
      Abeta(42) have been found in the PS1 gene. Here we have investigated the
      previously uncharacterized, very aggressive FAD mutation L166P that causes onset
      of AD in adolescence. Strikingly, the PS1 L166P mutation not only induces an
      exceptionally high increase of Abeta(42) production but also impairs NICD
      production and Notch signaling, as well as AICD generation. Thus, FAD-associated
      PS mutants cannot only affect the generation of NICD, but also that of AICD.
      Moreover, further analysis with artificial L166 mutants revealed that the gamma
      secretase cleavage at position 40/42 and the S3-like gamma-secretase cleavage at
      position 49 of the Abeta domain are both differentially affected by PS1 L166
      mutants. Finally, we show that PS1 L166 mutants affect the generation of NICD and
      AICD in a similar manner, supporting the concept that S3 protease and S3-like
      gamma-secretase cleavages are mediated by identical proteolytic activities.

PMID- 12048240
TI  - RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA
      are edited by adenosine deaminases that act on RNA.
AB  - Adenosine deaminases that act on RNA (ADARs) constitute a family of RNA-editing
      enzymes that convert adenosine to inosine within double-stranded regions of RNA.
      We previously developed a method to identify inosine-containing RNAs and used it
      to identify five ADAR substrates in Caenorhabditis elegans. Here we use the same
      method to identify five additional C. elegans substrates, including three mRNAs
      that encode proteins known to affect neuronal functions. All 10 of the C. elegans
      substrates are edited in long stem-loop structures located in noncoding regions,
      and thus contrast with previously identified substrates of other organisms, in
      which ADARs target codons. To determine whether editing in noncoding regions was
      a conserved ADAR function, we applied our method to poly(A)+ RNA of human brain
      and identified 19 previously unknown ADAR substrates. The substrates were
      strikingly similar to those observed in C. elegans, since editing was confined to
      3' untranslated regions, introns, and a noncoding RNA. Also similar to what was
      found in C. elegans, 15 of the 19 substrates were edited in repetitive elements.
      The identities of the newly identified ADAR substrates suggest that RNA editing
      may influence many biologically important processes, and that for many metazoa, A
      to-I conversion in coding regions may be the exception rather than the rule.

PMID- 12048241
TI  - Preferential cleavage of plasmid-based R-loops and D-loops by Drosophila
      topoisomerase IIIbeta.
AB  - The topoisomerase (topo) III enzymes are found in organisms ranging from bacteria
      to humans, yet the precise cellular function of these enzymes remains to be
      determined. We previously found that Drosophila topo IIIbeta can relax plasmid
      DNA only if the DNA is first hypernegatively supercoiled. To investigate the
      possibility that topo IIIbeta requires a single-stranded region for its
      relaxation activity, we formed R-loops and D-loops in plasmids. In addition to
      containing a single-stranded region, these R-loops and D-loops have the advantage
      of being covalently closed and supercoiled, thus allowing us to assay for
      supercoil relaxation. We found that topo IIIbeta preferentially cleaves, rather
      than relaxes, these substrates. The cleavage of the R-loops and D-loops, which is
      primarily in the form of nicking, occurs to a greater extent at a temperature
      that is lower than the optimal temperature for relaxation of hypernegatively
      supercoiled plasmid. In addition, the cleavage can be readily reversed by high
      salt or high temperature, and the products fail to enter the gel in the absence
      of proteinase K treatment and are not observed with an active-site Y332F mutant
      of topo IIIbeta, indicating that the cleavage is mediated by a topoisomerase. We
      mapped the cleavage to the unpaired strand within the loop region and found that
      the cleavage occurs along the length of the unpaired strand. These studies
      suggest that the topo III enzyme behaves as a structure-specific endonuclease in
      vivo, providing a reversible DNA cleavage activity that is specific for unpaired
      regions in the DNA.

PMID- 12048242
TI  - Mechanism of calcium/calmodulin inhibition of rod cyclic nucleotide-gated
      channels.
AB  - Rod cyclic nucleotide-gated (CNG) channels are heterotetramers comprised of both
      CNGA1 and CNGB1 subunits. Calcium/calmodulin (Ca(2+)/CaM) binds to a site in the
      N-terminal region of CNGB1 subunits and inhibits the opening conformational
      change in CNGA1/CNGB1 channels. Here, we show that polypeptides derived from an N
      terminal region of CNGB1 form a specific interaction with polypeptides derived
      from a C-terminal region of CNGA1 that is distal to the cyclic nucleotide-binding
      domain. Deletion of the Ca(2+)/CaM-binding site from the N-terminal region of
      CNGB1 eliminated both Ca(2+)/CaM modulation of the channel and the intersubunit
      interaction. Furthermore, the interaction was disrupted by the presence of
      Ca(2+)/CaM. These results suggest that Ca(2+)/CaM-dependent inhibition of rod
      channels is caused by the direct binding of Ca(2+)/CaM to a site in the N
      terminal region in CNGB1, which disrupts the interaction between this region and
      a distal C-terminal region of CNGA1. The mechanism underlying Ca(2+)/CaM
      modulation of rod channels is distinct from that in olfactory (CNGA2) CNG
      channels.

PMID- 12048243
TI  - Direct, activating interaction between glycogen synthase kinase-3beta and p53
      after DNA damage.
AB  - Glycogen synthase kinase-3beta (GSK3beta) is a central figure in Wnt signaling,
      in which its activity is controlled by regulatory binding proteins. Here we show
      that binding proteins outside the Wnt pathway also control the activity of
      GSK3beta. DNA damage induced by camptothecin, which activates the tumor
      suppressor p53, was found to activate GSK3beta. This activation occurred by a
      phosphorylation-independent mechanism involving direct binding of GSK3beta to
      p53, which was confined to the nucleus where p53 is localized, and mutated p53
      (R175H) bound but did not activate GSK3beta. Activation of GSK3 promoted
      responses to p53 including increases in p21 levels and caspase-3 activity. Thus,
      after DNA damage there is a direct interaction between p53 and GSK3beta, and
      these proteins act in concert to regulate cellular responses to DNA damage.

PMID- 12048244
TI  - A negative feedback system between oocyte bone morphogenetic protein 15 and
      granulosa cell kit ligand: its role in regulating granulosa cell mitosis.
AB  - Although the existence of a regulatory paracrine feedback system between oocytes
      and follicular somatic cells has been postulated for some time, there has not yet
      been any definitive evidence that such a communication system exists. Herein we
      present a previously undescribed oocyte-granulosa cell (GC) feedback
      communication system involving an oocyte-derived factor, bone morphogenetic
      protein-15 (BMP-15) and a GC-derived factor, kit ligand (KL), both of which have
      been shown to be crucial regulators of female reproduction. We used a coculture
      system of rat oocytes and GCs and found that BMP-15 stimulates KL expression in
      GCs, whereas KL inhibits BMP-15 expression in oocytes, thus forming a negative
      feedback loop. Moreover, KL, like BMP-15, exhibited mitotic activity on GCs in
      the presence of oocytes. Because c-kit (KL receptor) is expressed in oocytes but
      not GCs, the oocytes must be involved in mediating the KL-induced GC mitosis.
      Furthermore, the blockage of c-kit signaling in oocytes by using a c-kit
      neutralizing antibody markedly suppressed BMP-15-induced GC mitosis, suggesting
      that the oocyte must play a role in the GC responses to BMP-15. In contrast, the
      c-kit antibody had no effect on the mitotic activities of two other known GC
      mitogens, activin-A and BMP-7. Altogether, this study presents direct evidence of
      a negative feedback system governed by oocyte-derived BMP-15 and GC-derived KL,
      and demonstrates that the mitotic activities of BMP-15 and KL for GCs depend on
      this oocyte-GC communication system. We hypothesize that the negative feedback
      system most likely plays a pivotal role in early folliculogenesis.

PMID- 12048245
TI  - MEKK1 plays a critical role in activating the transcription factor C/EBP-beta
      dependent gene expression in response to IFN-gamma.
AB  - IFN-gamma induces a number of genes to up-regulate cellular responses by using
      specific transcription factors and the cognate elements. We recently discovered
      that CCAAT/enhancer-binding protein-beta (C/EBP-beta) induces gene transcription
      through an IFN-response element called gamma-IFN-activated transcriptional
      element (GATE). Using mutant cells, chemical inhibitors, and specific dominant
      negative inhibitors, we show that induction of GATE-driven gene expression
      depends on MEK1 (mitogen-activated protein kinase kinase/extracellular signal
      regulated protein kinase kinase) and ERKs (extracellular signal-regulated protein
      kinases) but is independent of Raf-1. Interestingly in cells lacking the MEKK1
      gene or expressing the dominant negative MEKK1, ERK activation, and GATE
      dependent gene expression is inhibited. A dominant negative MEKK1 blocks C/EBP
      beta-driven gene expression stimulated by IFN-gamma. These studies describe an
      IFN-gamma-stimulated pathway that involves MEKK1-MEK1-ERK1/2 kinases to regulate
      C/EBP-beta-dependent gene expression.

PMID- 12048246
TI  - Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and
      vascular endothelial growth factor (VEGF).
AB  - Multiple classes of factors contribute to angiogenesis. In past years, the
      primary focus has been to understand the functions of individual classes of
      angiogenic factors. However, few studies have focused on the combinatorial roles
      of multiple classes of factors in angiogenesis. In this report, we have
      investigated the in vivo angiogenic processes regulated by two major classes of
      angiogenic factors, the angiopoietins and vascular endothelial growth factor
      (VEGF). Here we show that angiopoietin-1, a factor previously considered to be
      proangiogenic, can offset VEGF-induced angiogenesis in vivo. We also provide
      direct in vivo evidence for the synergistic effect of angiopoietin-2 and VEGF on
      the induction of angiogenesis. Furthermore, we show that these two classes of
      factors control the ratio of arterial and venous blood vessel types during
      angiogenesis. We believe that our study is a step toward understanding how
      multiple classes of factors harmonize angiogenesis and blood vessel types.

PMID- 12048247
TI  - TAR RNA loop: a scaffold for the assembly of a regulatory switch in HIV
      replication.
AB  - Replication of HIV requires the Tat protein, which activates elongation of RNA
      polymerase II transcription at the HIV-1 promoter by interacting with the cyclin
      T1 (CycT1) subunit of the positive transcription elongation factor complex b (P
      TEFb). The transactivation domain of Tat binds directly to the CycT1 subunit of P
      TEFb and induces loop sequence-specific binding of P-TEFb onto nascent HIV-1
      trans-activation responsive region (TAR) RNA. We used systematic RNA-protein
      photocross-linking, Western blot analysis, and protein footprinting to show that
      residues 252-260 of CycT1 interact with one side of the TAR RNA loop and enhance
      interaction of Tat residue K50 to the other side of the loop. Our results show
      that TAR RNA provides a scaffold for two protein partners to bind and assemble a
      regulatory switch in HIV replication. RNA-mediated assembly of RNA-protein
      complexes could be a general mechanism for stable ribonucleoprotein complex
      formation and a key step in regulating other cellular processes and viral
      replication.

PMID- 12048249
TI  - The change in oceanic O(2) inventory associated with recent global warming.
AB  - Oceans general circulation models predict that global warming may cause a
      decrease in the oceanic O(2) inventory and an associated O(2) outgassing. An
      independent argument is presented here in support of this prediction based on
      observational evidence of the ocean's biogeochemical response to natural warming.
      On time scales from seasonal to centennial, natural O(2) flux/heat flux ratios
      are shown to occur in a range of 2 to 10 nmol of O(2) per joule of warming, with
      larger ratios typically occurring at higher latitudes and over longer time
      scales. The ratios are several times larger than would be expected solely from
      the effect of heating on the O(2) solubility, indicating that most of the O(2)
      exchange is biologically mediated through links between heating and
      stratification. The change in oceanic O(2) inventory through the 1990s is
      estimated to be 0.3 +/- 0.4 x 10(14) mol of O(2) per year based on scaling the
      observed anomalous long-term ocean warming by natural O(2) flux/heating ratios
      and allowing for uncertainty due to decadal variability. Implications are
      discussed for carbon budgets based on observed changes in atmospheric O(2)/N(2)
      ratio and based on observed changes in ocean dissolved inorganic carbon.

PMID- 12048248
TI  - Crystal structures of the vitamin D-binding protein and its complex with actin:
      structural basis of the actin-scavenger system.
AB  - Actin is the most abundant protein in eukaryotic cells, but its release from
      cells into blood vessels can be lethal, being associated with clinical situations
      including hepatic necrosis and septic shock. A homeostatic mechanism, termed the
      actin-scavenger system, is responsible for the depolymerization and removal of
      actin from the circulation. During the first phase of this mechanism, gelsolin
      severs the actin filaments. In the second phase, the vitamin D-binding protein
      (DBP) traps the actin monomers, which accelerates their clearance. We have
      determined the crystal structures of DBP by itself and complexed with actin to
      2.1 A resolution. Similar to its homologue serum albumin, DBP consists of three
      related domains. Yet, in DBP a strikingly different organization of the domains
      gives rise to a large actin-binding cavity. After complex formation the three
      domains of DBP move slightly to "clamp" onto actin subdomain 3 and to a lesser
      extent subdomain 1. Contacts between actin and DBP throughout their extensive
      3,454-A(2) intermolecular interface involve a mixture of hydrophobic,
      electrostatic, and solvent-mediated interactions. The area of actin covered by
      DBP within the complex approximately equals the sum of those covered by gelsolin
      and profilin. Moreover, certain interactions of DBP with actin mirror those
      observed in the actin-gelsolin complex, which may explain how DBP can compete
      effectively with gelsolin for actin binding. Formation of the strong actin-DBP
      complex proceeds with limited conformational changes to both proteins,
      demonstrating how DBP has evolved to become an effective actin-scavenger protein.

PMID- 12048250
TI  - A new form of cerebellar long-term potentiation is postsynaptic and depends on
      nitric oxide but not cAMP.
AB  - Long-term depression (LTD) at cerebellar parallel fiber (PF)-Purkinje cell
      synapses must be balanced by long-term potentiation (LTP) to prevent saturation
      and allow reversal of motor learning. The only previously analyzed form of
      cerebellar LTP is induced by 4-8 Hz PF stimulation and requires cAMP but not
      nitric oxide. It is a poor candidate to reverse LTD because it is presynaptically
      expressed whereas LTD is postsynaptic. We now characterize a new form of LTP
      induced by 1 Hz PF stimulation for at least 300 s. This LTP is postsynaptically
      expressed, enhanced by chelating postsynaptic Ca(2+), and depends on nitric oxide
      but not cAMP or cGMP, making it a plausible anti-Hebbian counterpart to Hebbian
      LTD.

PMID- 12048251
TI  - Dendritic K+ channels contribute to spike-timing dependent long-term potentiation
      in hippocampal pyramidal neurons.
AB  - We investigated the role of A-type K(+) channels for the induction of long-term
      potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal
      neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were
      paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl
      d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back
      propagating action potentials were boosted in the dendrites only when they were
      coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD
      098059 or U0126 shifted the activation of dendritic K(+) channels to more
      hyperpolarized potentials, reduced the boosting of dendritic action potentials by
      EPSPs, and suppressed the induction of LTP. These results support the hypothesis
      that dendritic K(+) channels and the boosting of back-propagating action
      potentials contribute to the induction of LTP in CA1 neurons.

PMID- 12048252
TI  - In vitro trans-differentiation of adult hepatic stem cells into pancreatic
      endocrine hormone-producing cells.
AB  - Although organ-specific stem cells possess plasticity that permit differentiation
      along new lineages, production of endocrine pancreas and insulin-secreting beta
      cells from adult nonpancreatic stem cells has not been demonstrated. We present
      evidence that highly purified adult rat hepatic oval "stem" cells, which are
      capable of differentiation to hepatocytes and bile duct epithelium, can trans
      differentiate into pancreatic endocrine hormone-producing cells when cultured in
      a high-glucose environment. These differentiated cells can self-assemble to form
      three-dimensional islet cell-like clusters that express pancreatic islet cell
      differentiation-related transcripts detectable by reverse transcription
      PCR/nested PCR (e.g., PDX-1, PAX-4, PAX-6, Nkx2.2 and Nkx6.1, insulin I, insulin
      II, glucose transporter 2, and glucagon) and islet-specific hormones detectable
      by immunocytochemistry (e.g., insulin, glucagon, and pancreatic polypeptide). In
      addition, these cells concomitantly lose expression of the hepatocyte protein Hep
      par. When stimulated with glucose, these cells synthesize and secrete insulin, a
      response enhanced by nicotinamide. In a pilot study, the oval cell-derived islet
      cell-like clusters displayed the ability to reverse hyperglycemia in a diabetic
      NOD-scid mouse. These results indicate that primary adult liver stem cells can
      differentiate in a nonlineage-restricted manner. Trans-differentiation into
      endocrine pancreas could have significant implications for future therapies of
      diabetes.

PMID- 12048253
TI  - The RecA proteins of Deinococcus radiodurans and Escherichia coli promote DNA
      strand exchange via inverse pathways.
AB  - The RecA protein of Escherichia coli, and all filament-forming homologues
      identified to date, promote DNA strand exchange by a common, ordered pathway. A
      filament is first formed on single-stranded DNA, followed by uptake of the duplex
      substrate. These proteins are thereby targeted to single-strand gaps and tails
      where recombinational DNA repair is required. The observed course of DNA strand
      exchange promoted by the RecA protein from the extremely radioresistant bacterium
      Deinococcus radiodurans is the exact inverse of this established pathway. This
      reaction lies at the heart of a remarkably efficient system for the repair of DNA
      damage.

PMID- 12048254
TI  - Identification of the enzymatic mechanism of nitroglycerin bioactivation.
AB  - Nitroglycerin (glyceryl trinitrate, GTN), originally manufactured by Alfred
      Nobel, has been used to treat angina and heart failure for over 130 years.
      However, the molecular mechanism of GTN biotransformation has remained a mystery
      and it is not well understood why "tolerance" (i.e., loss of clinical efficacy)
      manifests over time. Here we purify a nitrate reductase that specifically
      catalyzes the formation of 1,2-glyceryl dinitrate and nitrite from GTN, leading
      to production of cGMP and relaxation of vascular smooth muscle both in vitro and
      in vivo, and we identify it as mitochondrial aldehyde dehydrogenase (mtALDH). We
      also show that mtALDH is inhibited in blood vessels made tolerant by GTN. These
      results demonstrate that the biotransformation of GTN occurs predominantly in
      mitochondria through a novel reductase action of mtALDH and suggest that nitrite
      is an obligate intermediate in generation of NO bioactivity. The data also
      indicate that attenuated biotransformation of GTN by mtALDH underlies the
      induction of nitrate tolerance. More generally, our studies provide new insights
      into subcellular processing of NO metabolites and suggest new approaches to
      generating NO bioactivity and overcoming nitrate tolerance.

PMID- 12048255
TI  - Documenting a significant relationship between macroevolutionary origination
      rates and Phanerozoic pCO2 levels.
AB  - We show that the rates of diversification of the marine fauna and the levels of
      atmospheric CO(2) have been closely correlated for the past 545 million years.
      These results, using two of the fundamental databases of the Earth's biota and
      the Earth's atmospheric composition, respectively, are highly statistically
      significant (P < 0.001). The strength of the correlation suggests that one or
      more environmental variables controlling CO(2) levels have had a profound impact
      on evolution throughout the history of metazoan life. Comparing our work with
      highly significant correlations described by D. H. Rothman [Rothman, D. H. (2001)
      Proc. Natl. Acad. Sci. USA 98, 4305-4310] between total biological diversity and
      a measure of stable carbon isotope fractionation, we find that the rates of
      diversification rather than total diversification correlate with environmental
      variables, and that the rate of diversification follows the record of CO(2)
      projected by R. A. Berner and Z. Kothavala [Berner, R. A. & Kothavala, Z. (2001)
      Am. J. Sci. 301, 182-204] more closely than that predicted by Rothman.

PMID- 12048256
TI  - Coactivator/corepressor ratios modulate PR-mediated transcription by the
      selective receptor modulator RU486.
AB  - Selective receptor modulators, such as the antiprogestin RU486, are known to
      exhibit partial agonist activities in a cell-type-dependent manner. Employing an
      in vitro chromatin transcription system that recapitulates progesterone receptor
      (PR)-mediated transcription in vivo, we have investigated the molecular basis by
      which the antiprogestin RU486 regulates transcription in a cell-type-specific
      manner. We have compared the effects of RU486 on PR-dependent transcription in
      vitro using T47D and HeLa cell nuclear extracts. RU486 exhibits a differential
      ability to activate transcription within these two cell types. The differential
      effect on transcription correlates with different ratios of endogenous
      coactivators/corepressors in these cells. Unlike agonist-bound PR that interacts
      only with coactivators such as steroid receptor coactivator-1 (SRC-1), RU486
      bound PR binds to both coactivator SRC-1 and corepressor silencing mediator for
      retinoid and thyroid hormone receptor (SMRT) in vitro. Both SRC-1 and SMRT have
      the capacity to modulate RU486-dependent activity. Moreover, a change in the
      relative levels of SRC-1 and SMRT contained in our chromatin transcription system
      modulates agonist/antagonist effects of RU486 on transcription by PR. Our data
      indicate that the ability of RU486 to activate transcription is modulated by the
      ratio of coactivators to corepressors and substantiate the important roles of
      coregulators in the regulation of steroid receptor mediated transactivation in
      response to selective receptor modulators.

PMID- 12048257
TI  - 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced
      proliferation of mesangial cells via modulation of Rho GTPase/ p21 signaling
      pathway: Implications for diabetic nephropathy.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase, also known as
      statins, are lipid-lowering agents widely used in the prevention of coronary
      heart disease. Recent experimental and clinical data, however, indicate that the
      overall benefits of statin therapy may exceed its cholesterol-lowering
      properties. We postulate that statins may ameliorate the detrimental effects of
      high glucose (HG)-induced proliferation of mesangial cells (MCs), a feature of
      early stages of diabetic nephropathy, by preventing Rho isoprenylation. Rat MCs
      cultured in HG milieu were treated with and without simvastatin, an HMG-CoA
      reductase inhibitor. Simvastatin inhibited HG-induced MC proliferation as
      measured by [(3)H]thymidine incorporation. This inhibitory effect was reversed
      with geranylgeranyl pyrophosphate, an isoprenoid intermediate of the cholesterol
      biosynthetic pathway. At the cell-cycle level, the HG-induced proliferation of
      MCs was associated with a decrease in cyclin dependent kinase (CDK) inhibitor p21
      protein expression accompanied by an increase in CDK4 and CDK2 kinase activities.
      Simvastatin reversed the down-regulation of p21 protein expression and decreased
      CDK4 and CDK2 kinase activities. Exposure of MCs to HG was associated with an
      increase in membrane-associated Ras and Rho GTPase protein expression.
      Cotreatment of MCs with simvastatin reversed HG-induced Ras and Rho membrane
      translocation. Immunofluorescence microscopy revealed that the overexpression of
      the dominant-negative RhoA led to a significant increase in p21 expression. Our
      data suggest that simvastatin represses the HG-induced Rho GTPase/p21 signaling
      in glomerular MCs. Thus, this study provides a molecular basis for the use of
      statins, independently of their cholesterol-lowering effect, in early stages of
      diabetic nephropathy.

PMID- 12048258
TI  - A gene network model accounting for development and evolution of mammalian teeth.
AB  - Generation of morphological diversity remains a challenge for evolutionary
      biologists because it is unclear how an ultimately finite number of genes
      involved in initial pattern formation integrates with morphogenesis. Ideally,
      models used to search for the simplest developmental principles on how genes
      produce form should account for both developmental process and evolutionary
      change. Here we present a model reproducing the morphology of mammalian teeth by
      integrating experimental data on gene interactions and growth into a
      morphodynamic mechanism in which developing morphology has a causal role in
      patterning. The model predicts the course of tooth-shape development in different
      mammalian species and also reproduces key transitions in evolution. Furthermore,
      we reproduce the known expression patterns of several genes involved in tooth
      development and their dynamics over developmental time. Large morphological
      effects frequently can be achieved by small changes, according to this model, and
      similar morphologies can be produced by different changes. This finding may be
      consistent with why predicting the morphological outcomes of molecular
      experiments is challenging. Nevertheless, models incorporating morphology and
      gene activity show promise for linking genotypes to phenotypes.

PMID- 12048260
TI  - Prevention and treatment of lymphatic metastasis by antilymphangiogenic therapy.

PMID- 12048261
TI  - "Build quality in"--HER2 testing in the real world.

PMID- 12048259
TI  - Presenilin and nicastrin regulate each other and determine amyloid beta-peptide
      production via complex formation.
AB  - Amyloid beta-peptide (Abeta) is generated by the consecutive cuts of two membrane
      bound proteases. Beta-secretase cuts at the N terminus of the Abeta domain,
      whereas gamma-secretase mediates the C-terminal cut. Recent evidence suggests
      that the presenilin (PS) proteins, PS1 and PS2, may be gamma-secretases. Because
      PSs principally exist as high molecular weight protein complexes, biologically
      active gamma-secretases likely require other cofactors such as nicastrin (Nct)
      for their activities. Here we show that preferentially mature Nct forms a stable
      complex with PSs. Furthermore, we have down-regulated Nct levels by using a
      highly specific and efficient RNA interference approach. Very similar to a loss
      of PS function, down-regulation of Nct levels leads to a massive accumulation of
      the C-terminal fragments of the beta-amyloid precursor protein. In addition,
      Abeta production was markedly reduced. Strikingly, down-regulation of Nct
      destabilized PS and strongly lowered levels of the high molecular weight PS1
      complex. Interestingly, absence of the PS1 complex in PS1(-/-) cells was
      associated with a strong down-regulation of the levels of mature Nct, suggesting
      that binding to PS is required for trafficking of Nct through the secretory
      pathway. Based on these findings we conclude that Nct and PS regulate each other
      and determine gamma-secretase function via complex formation.

PMID- 12048262
TI  - Collaboration to play key role in NCI's future, director says. Interview by
      Katherine Arnold.

PMID- 12048263
TI  - Silence of the genes: cancer epigenetics arrives.

PMID- 12048265
TI  - Movies of metastasis shed light on how cells move in the body.

PMID- 12048266
TI  - Government sets compensation guidelines for radiation exposure.

PMID- 12048267
TI  - Risk charts: putting cancer in context.

PMID- 12048268
TI  - Cancer immunotherapy with peptide-based vaccines: what have we achieved? Where
      are we going?
AB  - Many human tumor-associated antigens (TAAs) have recently been identified and
      molecularly characterized. When bound to major histocompatibility complex
      molecules, TAA peptides are recognized by T cells. Clinical studies have
      therefore been initiated to assess the therapeutic potential of active
      immunization or vaccination with TAA peptides in patients with metastatic cancer.
      So far, only a limited number of TAA peptides, mostly those recognized by CD8(+)
      T cells in melanoma patients, have been clinically tested. In some clinical
      trials, partial or complete tumor regression was observed in approximately 10%
      30% of patients. No serious side effects have been reported. The clinical
      responses, however, were often not associated with a detectable T-cell-specific
      antitumor immune response when patients' T cells were evaluated in ex vivo
      assays. In this review, we analyze the available human TAA peptides, the
      potential immunogenicity (i.e., the ability to trigger a tumor-specific T-cell
      response) of TAA peptides in vitro and ex vivo, and the potential to construct
      slightly modified forms of TAA peptides that have increased T-cell stimulatory
      activity. We discuss the available data from clinical trials of TAA peptide-based
      vaccination (including those that used dendritic cells to present TAA peptides),
      identify possible reasons for the limited clinical efficacy of these vaccines,
      and suggest ways to improve the clinical outcome of TAA peptide-based vaccination
      for cancer patients.

PMID- 12048269
TI  - Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking
      vascular endothelial growth factor receptor 3 signaling.
AB  - BACKGROUND: Vascular endothelial growth factor C (VEGF-C) stimulates tumor
      lymphangiogenesis (i.e., formation of lymphatic vessels) and metastasis to
      regional lymph nodes by interacting with VEGF receptor 3 (VEGFR-3). We sought to
      determine whether inhibiting VEGFR-3 signaling, and thus tumor lymphangiogenesis,
      would inhibit tumor metastasis. METHODS: We used the highly metastatic human lung
      cancer cell line NCI-H460-LNM35 (LNM35) and its parental line NCI-H460-N15 (N15)
      with low metastatic capacity. We inserted genes by transfection and established a
      stable N15 cell line secreting VEGF-C and a LNM35 cell line secreting the soluble
      fusion protein VEGF receptor 3-immunoglobulin (VEGFR-3-Ig, which binds VEGF-C and
      inhibits VEGFR-3 signaling). Control lines were transfected with mock vectors.
      Tumor cells were implanted subcutaneously into severe combined immunodeficient
      mice (n = 6 in each group), and tumors and metastases were examined 6 weeks
      later. In another approach, recombinant adenoviruses expressing VEGFR-3-Ig (AdR3
      Ig) or beta-galactosidase (AdLacZ) were injected intravenously into LNM35 tumor
      bearing mice (n = 14 and 7, respectively). RESULTS: LNM35 cells expressed higher
      levels of VEGF-C RNA and protein than did N15 cells. Xenograft mock vector
      transfected LNM35 tumors showed more intratumoral lymphatic vessels (15.3 vessels
      per grid; 95% confidence interval [CI] = 13.3 to 17.4) and more metastases in
      draining lymph nodes (12 of 12) than VEGFR-3-Ig-transfected LNM35 tumors (4.1
      vessels per grid; 95% CI = 3.4 to 4.7; P<.001, two-sided t test; and four lymph
      nodes with metastases of 12 lymph nodes examined). Lymph node metastasis was also
      inhibited in AdR3-Ig-treated mice (AdR3-Ig = 0 of 28 lymph nodes; AdLacZ = 11 of
      14 lymph nodes). However, metastasis to the lungs occurred in all mice,
      suggesting that LNM35 cells can also spread via other mechanisms. N15 tumors
      overexpressing VEGF-C contained more lymphatic vessels than vector-transfected
      tumors but did not have increased metastatic ability. CONCLUSIONS: Lymph node
      metastasis appears to be regulated by additional factors besides VEGF-C.
      Inhibition of VEGFR-3 signaling can suppress tumor lymphangiogenesis and
      metastasis to regional lymph nodes but not to lungs.

PMID- 12048270
TI  - Household stove improvement and risk of lung cancer in Xuanwei, China.
AB  - BACKGROUND: Lung cancer rates in rural Xuanwei County, Yunnan Province, are among
      the highest in China. Residents traditionally burned "smoky" coal in unvented
      indoor firepits that generated very high levels of air pollution. Since the
      1970s, most residents have changed from firepits to stoves with chimneys. This
      study assessed whether lung cancer incidence decreased after this stove
      improvement. METHODS: A cohort of 21 232 farmers, born from 1917 through 1951,
      was followed retrospectively from 1976 through 1992. All subjects were users of
      smoky coal who had been born into homes with unvented firepits. During their
      lifetime, 17 184 subjects (80.9%) changed permanently to stoves with chimneys. A
      hospital record search detected 1384 cases of lung cancer (6.5%) during follow
      up. Associations of stove improvement with lung cancer incidence were analyzed
      with product-limit plots and multivariable Cox models. In 1995, indoor
      concentrations of airborne particles and benzo[a]pyrene were compared in Xuanwei
      homes during smoky coal burning in stoves with chimneys and in unvented stoves or
      firepits. RESULTS: A long-term reduction in lung cancer incidence was noted after
      stove improvement. In Cox models, risk ratios (RRs) for lung cancer after stove
      improvement were 0.59 (95% confidence interval [CI] = 0.49 to 0.71) in men and
      0.54 (95% CI = 0.44 to 0.65) in women (for both, P<.001). Incidence reduction
      became unequivocal about 10 years after stove improvement. Levels of indoor air
      pollution during burning with chimneys were less than 35% of levels during
      unvented burning. CONCLUSION: Changing from unvented to vented stoves appears to
      benefit the health of people in China and may do so in other developing countries
      as well.

PMID- 12048271
TI  - Validity of cancer registry data for measuring the quality of breast cancer care.
AB  - BACKGROUND: Various groups have called for a national system to monitor the
      quality of cancer care. The validity of cancer registry data for quality of
      cancer care has not been well studied. We investigated the validity of such
      information in the California Cancer Registry. METHODS: We compared registry data
      associated with care with data abstracted from the medical records of patients
      diagnosed with breast cancer. We also calculated a quality score for each subject
      by determining the proportion of four evidence-based quality indicators that were
      met and then compared overall quality scores obtained from registry and medical
      record data. All statistical tests were two-sided. RESULTS: Records of 304
      patients were studied. Compared with the medical record data gold standard, the
      accuracy of registry data was higher for hospital-based services (sensitivity =
      95.0% for mastectomy, 94.9% for lumpectomy, and 95.9% for lymph node dissection)
      than for ambulatory services (sensitivity = 9.8% for biopsy, 72.2% for radiation
      therapy, 55.6% for chemotherapy, and 36.2% for hormone therapy). On average,
      quality scores calculated from registry data were 11 percentage points (95%
      confidence interval [CI] = 9 to 13 percentage points, P<.001) lower than those
      calculated from medical record data. Quality scores calculated from registry data
      were 5 percentage points (95% CI = 3 to 7 percentage points) lower for patients
      with stage I breast cancer, 16 percentage points (95% CI = 12 to 20 percentage
      points) lower for patients with stage II breast cancer, and 20 percentage points
      (95% CI = 8 to 32 percentage points) lower for patients with stage III breast
      cancer than were corresponding scores calculated from medical record data (all
      P<.001). The greater difference in quality scores for stage II and III patients
      revealed that disease severity and setting of care affected the validity of
      registry data. CONCLUSIONS: Cancer registry data for quality measurement may not
      be valid for all care settings, but registries could provide the infrastructure
      for collecting data on the quality of cancer care. We urge that funding be
      increased to augment data collection by cancer registries.

PMID- 12048272
TI  - Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer
      model BRCAPRO.
AB  - BACKGROUND: Because BRCA gene mutation testing is costly, occasionally
      uninformative, and frequently associated with ethical and legal issues, careful
      patient selection is required prior to testing. Estimation of BRCA gene mutation
      probability is an important component of pretest counseling, but the accuracy of
      these estimates is currently unknown. We measured the performance of eight cancer
      risk counselors and of a computer model, BRCAPRO, at identifying families likely
      to carry a BRCA gene mutation. METHODS: Eight cancer risk counselors and the
      computer model BRCAPRO estimated BRCA gene mutation probabilities for 148
      pedigrees selected from an initial sample of 272 pedigrees. The final sample was
      limited to pedigrees with a proband affected by breast or ovarian cancer and
      BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or
      positive for a deleterious mutation. Sensitivity, specificity, negative
      predictive value, positive predictive value, and areas under receiver operator
      characteristics (ROC) curves were calculated for each risk counselor and for
      BRCAPRO. All statistical tests were two sided. RESULTS: Using a greater-than-10%
      BRCA gene mutation probability threshold, the median sensitivity for identifying
      mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and
      92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was
      16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for
      BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk
      counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for
      BRCAPRO (P =.04). There was a slight, but not statistically significant,
      improvement in all counselor performance measures when BRCAPRO-assigned gene
      mutation probability information was included with the pedigrees. CONCLUSIONS:
      Sensitivity for identifying BRCA gene mutation carriers is similar for
      experienced risk counselors and the computer model BRCAPRO. Because the computer
      model consistently demonstrated superior specificity, overall discrimination
      between BRCA gene mutation carriers and BRCA gene mutation noncarriers was
      slightly better for BRCAPRO.

PMID- 12048273
TI  - Real-world performance of HER2 testing--National Surgical Adjuvant Breast and
      Bowel Project experience.
AB  - Trastuzumab (Herceptin) provides clinical benefits for patients diagnosed with
      advanced breast cancers that have overexpressed the HER2 protein or have
      amplified the HER2 gene. The National Surgical Adjuvant Breast and Bowel Project
      (NSABP) Protocol B-31 is designed to test the advantage of adding Herceptin to
      the adjuvant chemotherapeutic regimen of doxorubicin and cyclophosphamide
      followed by paclitaxel (Taxol) in the treatment of stage II breast cancer with
      HER2 overexpression or gene amplification. Eligibility is based on HER2 assay
      results submitted by the accruing institutions. We conducted a central review of
      the first 104 cases entered in this trial on the basis of immunohistochemistry
      (IHC) results. We found that 18% of the community-based assays, which were used
      to establish the eligibility of patients to participate in the B-31 study, could
      not be confirmed by HercepTest IHC or fluorescence in situ hybridization (FISH)
      by a central testing facility. This report provides a snapshot of the quality of
      HER2 assays performed in laboratories nationwide.

PMID- 12048275
TI  - Loss of heterozygosity in benign breast epithelium in relation to breast cancer
      risk.
AB  - The multistage model of breast carcinogenesis suggests that errors in DNA
      replication and repair generate diversity in the breast epithelium (the mutator
      phenotype), resulting in selection and expansion of premalignant clones with an
      acquired survival advantage. We measured loss of heterozygosity (LOH) in breast
      epithelial cells obtained by random fine-needle aspiration (FNA) biopsy from 30
      asymptomatic women whose risk of breast cancer had been defined by the Gail
      model. Polymorphic microsatellite markers were selected on the basis of their
      relevance to breast cancer. Breast epithelium of 11 (37%) of 30 women had normal
      cytology, and that of 19 (63%) had proliferative cytology (eight with atypia and
      11 without atypia). LOH was detected in two women with normal cytology and in 14
      women (seven with atypia and seven without atypia) with proliferative cytology (P
      =.007). The frequency of LOH was associated with the cytological diagnosis, as
      well. The mean proportion (range) of informative markers demonstrating LOH was
      0.02 (0-0.20) for the 11 women with normal cytology, as compared with 0.15 (0
      0.50) for the 19 women with proliferative cytology (P =.02). Mean lifetime risk
      for developing breast cancer, as calculated by the Gail model, was 16.7% for
      women with no LOH compared with 22.9% for women with any LOH (P =.05). These
      observations support a multistage model of breast carcinogenesis where the
      initiating events are those that result in genomic instability. Accurate
      individualized breast cancer risk assessment may be possible based on molecular
      analysis of breast epithelial cells obtained by random FNA.

PMID- 12048274
TI  - Concordance between local and central laboratory HER2 testing in the breast
      intergroup trial N9831.
AB  - The efficacy of trastuzumab for metastases coupled with the relatively poor
      prognosis of patients with node-positive, HER2-positive breast cancer has led to
      the evaluation of trastuzumab as an adjuvant therapy. A prospective, randomized,
      three-arm, phase III trial is being conducted by the Breast Intergroup (N9831)
      for women with primary, operable, histologically confirmed, node-positive breast
      carcinoma that strongly overexpresses (3+) HER2 protein and/or displays HER2/neu
      gene amplification, as determined by local laboratory testing. The protocol
      requires confirmatory central testing of HER2 status using the HercepTest
      immunohistochemistry and the Vysis PathVysion fluorescence in situ hybridization
      (FISH) assays. Tumor specimens from the first 119 patients enrolled in N9831 were
      centrally tested; 74% were found to be HercepTest 3+ and 66% were found to have
      HER2 gene amplification. Only six of nine (67%) of the specimens submitted by
      local laboratories as FISH positive could be confirmed by central assays. The
      concordance for central HercepTest and central FISH assays was 92%. The poor
      concordance (74%) between local and central testing for HER2 status has led to
      modifications in the eligibility criteria for N9831.

PMID- 12048276
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048277
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048278
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048279
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048280
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048281
TI  - Re: All-cause mortality in randomized trials of cancer screening.

PMID- 12048284
TI  - Mapping cellular signaling.

PMID- 12048285
TI  - The merits of monitoring: should we follow all our rheumatoid arthritis patients
      in daily practice?

PMID- 12048286
TI  - The central nervous system in systemic lupus erythematosus. Part 1. Clinical
      syndromes: a literature investigation.
AB  - OBJECTIVES: To establish the central nervous system (CNS) manifestations of
      systemic lupus erythematosus (SLE) as described in the literature and to compare
      the results with two previously published classifications. METHODS: Using PUBMED,
      a systematic search was performed for publications from 1980 onwards on CNS
      syndromes of patients with SLE. A distinction was made between CNS syndromes
      induced by SLE and the CNS autoimmune diseases associated with SLE. Criteria were
      defined for inclusion of CNS syndromes or diseases as SLE-induced or SLE
      associated. RESULTS: The literature search yielded names of 30 syndromes and two
      diseases, but only 16 syndromes and one disease fulfilled the set of predefined
      criteria. Two syndromes-depression and anxiety-were predominantly psychological
      in origin in most patients; other syndromes were biological. DISCUSSION:
      Strengths and weaknesses of two classifications of CNS syndromes are evaluated.
      The older of the two is long and has not been accepted fully. Brevity is an
      advantage of the American College of Rheumatology (ACR) nomenclature system. A
      disadvantage of this system is the concealment of differences in health risks by
      the pooling of items. Furthermore, the items of the system do not all belong to
      the same dimension: one is pathological and the others are clinical. To remedy
      these drawbacks, we suggest the rephrasing and subdivision of items and that the
      predominantly psychopathological syndromes should be dealt with separately in
      epidemiological studies. CONCLUSIONS: SLE may induce 16 different clinical
      syndromes of the CNS and is occasionally associated with one other CNS autoimmune
      disease. A modification of the ACR nomenclature system is proposed.

PMID- 12048287
TI  - The central nervous system in systemic lupus erythematosus. Part 2. Pathogenetic
      mechanisms of clinical syndromes: a literature investigation.
AB  - OBJECTIVES: To identify the pathogenetic mechanisms of central nervous system
      (CNS) syndromes of systemic lupus erythematosus (SLE) as described in the
      literature. METHODS: Using PUBMED, we performed a systematic search of
      publications from 1980 onwards. Studies were eligible if they had been performed
      on patients or material from patients with CNS manifestations and definite SLE
      and when the CNS manifestations were not secondary. Criteria were formulated for
      the identification of pathogenetic mechanisms. RESULTS: The single most important
      cause of the CNS syndromes of SLE is ischaemia due to narrowing or occlusion of
      small vessels, arteries and veins. Antiphospholipid antibodies and premature
      atherosclerosis play roles in these processes, but they have not been delineated
      definitely. Intracranial and intraspinal haemorrhages are much less frequent than
      ischaemia and are presumably in part due directly to SLE. Vasculitis may cause
      ischaemia or haemorrhage in the CNS and is involved occasionally, as shown by
      imaging and histological findings. White matter damage is heterogeneous and ill
      understood. It includes white matter degeneration and myelin vacuolation of the
      spinal cord, and reversible leucoencephalopathy due to oedema. Antibody-induced
      neuronal dysfunction in the CNS is a realistic hypothesis and may involve anti
      ribosomal P antibodies and several other antibodies. Deficiency of psychological
      reactions forms a separate and entirely different category of mechanisms.
      CONCLUSIONS: Causes have been identified or possible causes have been suggested
      for most of the CNS syndromes of SLE, thus offering rationales for different
      forms of prevention and therapy.

PMID- 12048288
TI  - Infliximab and leflunomide combination therapy in rheumatoid arthritis: an open
      label study.
AB  - OBJECTIVE: To study the safety and efficacy of infliximab plus leflunomide
      combination therapy in adult rheumatoid arthritis (RA). METHODS: Twenty patients
      with active RA received leflunomide 100 mg for 3 days followed by 20 mg daily for
      32 weeks. At week 2 all patients started infliximab 3 mg/kg, and received a
      further four infusions at weeks 4, 8, 16 and 24. RESULTS: Adverse events led to
      11 patients being withdrawn before the end of the study. The commonest adverse
      event was pruritus associated with an eczematous rash. Other serious reactions
      included infliximab infusion reactions in four patients and Stevens-Johnson
      syndrome in one. There was no relationship between the serum concentration of A77
      1726, the active metabolite of leflunomide, and adverse events. The mean Disease
      Activity Score (DAS28) fell from 7.18 at week 0 to 5.18 (P<0.0001, paired t-test)
      at week 4 and remained between 3.85 and 4.85 up to week 32. In those patients
      remaining on treatment, more than 80% achieved an ACR20 response from week 8 to
      week 28, and up to 46% achieved an ACR70 response. CONCLUSION: Infliximab plus
      leflunomide combination therapy appears to be highly efficacious in the treatment
      of adult RA. However, widespread use may be limited by adverse events, which were
      common and in some cases severe.

PMID- 12048289
TI  - Dose titration using the Disease Activity Score (DAS28) in rheumatoid arthritis
      patients treated with anti-TNF-alpha.
AB  - OBJECTIVE: Anti-tumour necrosis factor alpha (TNF-alpha) therapy yields high
      response rates shortly after institution of therapy in patients with rheumatoid
      arthritis (RA), and on theoretical grounds large differences in the effective
      dose between patients can be expected. Together with the high costs, these
      differences warrant new approaches to the way patients are dosed. METHODS: We
      used the Disease Activity Score (DAS28), a composite disease activity index, to
      titrate the dose of anti-TNF-alpha (adalimumab, D2E7; Knoll) in 21 patients with
      low disease activity in an open extension study lasting 40 weeks. The dose of
      anti-TNF-alpha was reduced stepwise and dosing intervals were kept stable.
      Disease activity and flares were assessed using the DAS28. Patients who flared
      received the previous effective dose. RESULTS: Dose reduction was accomplished in
      15 patients. The total amount of anti-TNF-alpha given to the patients was reduced
      by 67%. At the end of the study the mean DAS28 had not changed and no patients
      dropped out because of persistent worsening of the RA. CONCLUSION: Dose titration
      of anti-TNF-alpha treatment using the DAS28 is feasible and leads to overall dose
      reduction while maintaining clinical efficacy. This approach will save costs and
      possibly prevent long-term side-effects.

PMID- 12048290
TI  - Clinical predictors of fetal and maternal outcome in systemic lupus
      erythematosus: a prospective study of 103 pregnancies.
AB  - OBJECTIVE: Our aim was to assess the outcome of pregnancy in a cohort of patients
      with SLE and to evaluate clinical and laboratory markers for fetal outcome and
      maternal flares. METHODS: Sixty patients with 103 pregnancies were evaluated
      prospectively between 1984 and 1999. RESULTS: There were 68 live births, 15
      spontaneous abortions, 12 stillbirths and eight therapeutic abortions. Of
      liveborn infant births, 19 were premature, 24 had suffered intrauterine growth
      restriction and one had neonatal lupus. Maternal lupus flares occurred in 33% of
      pregnancies, mostly in the second trimester (26%) and in the post-partum period
      (51%). Flares during pregnancy showed a statistically significant association
      with discontinuation of chloroquine treatment, a history of more than three
      flares before gestation, and a SLEDAI (Systemic Lupus Erythematosus Disease
      Activity Index) score of >or=5 in these flares. Antiphospholipid antibodies, C3
      hypocomplementaemia and hypertension during pregnancy were significantly
      associated with fetal loss, prematurity and intrauterine growth restriction.
      CONCLUSIONS: Patients with more active SLE and those with aPL antibodies and
      hypertension should be monitored and managed carefully during pregnancy.

PMID- 12048291
TI  - Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA
      B27.
AB  - OBJECTIVE: To investigate the influence of the major histocompatibility complex
      (MHC) class I molecule HLA-B27 on (i) the invasion of Salmonella and Yersinia
      into human intestinal epithelial cells, (ii) the survival of intracellular
      Salmonella in these cells, and (iii) the production of certain inflammatory
      cytokines by the cells after Salmonella infection. METHODS: The human intestinal
      epithelial cell line Henle-407 was transfected with HLA-B27 DNA. These cells and
      HLA-B27-negative control cells were infected with Salmonella or Yersinia, and
      viable intracellular bacteria were determined as colony-forming units. Cytokine
      production was assayed with ELISA. RESULTS: Salmonella invaded HLA-B27-positive
      Henle cells in higher numbers than HLA-B27-negative control cells. However, HLA
      B27 did not affect the invasion of Yersinia or the survival of the intracellular
      bacteria in these intestinal epithelial cells. Salmonella infection induced
      production of interleukin-8 (IL-8), IL-6 and monocyte chemotactic protein 1 (MCP
      1) by Henle cells that was not affected by HLA-B27 in a specific way.
      CONCLUSIONS: These findings suggest that HLA-B27 enhances the invasion of
      Salmonella into intestinal epithelial cells. The interaction between bacteria and
      intestinal epithelial cells plays an important role during the early phases of
      ReA. HLA-B27-linked modulation of Salmonella invasion may lead to an increased
      load of Salmonella in intestinal tissue and thus increased susceptibility to
      reactive arthritis.

PMID- 12048292
TI  - Homocysteine and folate status in methotrexate-treated patients with rheumatoid
      arthritis.
AB  - OBJECTIVE: To study (i) the influence of methotrexate (MTX) therapy on
      homocysteine and folate metabolism in patients with rheumatoid arthritis (RA),
      (ii) the influence of the C677T mutation in the methylenetetrahydrofolate
      reductase gene (MTHFR) on the change in plasma homocysteine levels during MTX
      treatment, and (iii) the interference of folate and homocysteine metabolism with
      the efficacy and toxicity of treatment with MTX. METHODS: The 113 patients
      enrolled in this study were participating in a 48-week, multicentre, double
      blind, placebo-controlled study comparing the efficacy and toxicity of MTX
      treatment with and without folic or folinic acid supplementation. The MTX dose
      was 7.5 mg/week initially and increased to a maximum of 25 mg/week if necessary.
      Concentrations of total folate, 5-methyl tetrahydrofolate (in serum and in
      erythrocytes) and of homocysteine, cysteine and cysteine-glycine and the MTHFR
      genotype were determined before the start of the study, after 6 weeks, and after
      48 weeks or on withdrawal from the study. Blood was drawn from fasting patients
      at a standardized time in the morning, 16 h after intake of MTX. The laboratory
      results were related to parameters of efficacy and toxicity of MTX treatment.
      RESULTS: Baseline values were distributed equally in the three treatment groups.
      The mean plasma homocysteine level (normal range 6-15 micromol/l) before the
      start of MTX was relatively high in all groups: 15.4 micromol/l [95% confidence
      interval (CI) 13.5 to 17.2] in the MTX plus placebo group (n=39), 14.3 micromol/l
      (95% CI 12.2 to 16.4) in the MTX plus folic acid group (n=35) and 15.9 micromol/l
      (95% CI 13.7 to 18.1) in the MTX plus folinic acid group (n=39). After 48 weeks
      of MTX therapy, the mean homocysteine level showed an increase in the placebo
      group (+3.6 micromol/l, 95% CI 1.7 to 5.6). In contrast, a decrease was observed
      in the groups supplemented with folic or folinic acid (folic acid, -2.7
      micromol/l, 95% CI -1.4 to -4.0; folinic acid, -1.6 micromol/l, 95% CI -0.1 to 
      3.0). The differences in the change in plasma homocysteine level between the
      placebo group and each of the two folate-supplemented groups were statistically
      significant (P<0.0001), contrary to the difference between the folic and folinic
      acid groups (P=0.26). Linear regression analysis showed that the change in plasma
      homocysteine level was statistically significantly associated with folic or
      folinic acid supplementation (P=0.0001) but not with the presence or absence of
      the C677T mutation in the MTHFR gene. Homozygous mutants had a higher plasma
      homocysteine concentration at baseline. No relationship was found between the
      change in disease activity and the change in homocysteine concentration or the
      mean homocysteine concentration after 48 weeks of MTX therapy. Toxicity-related
      discontinuation of MTX treatment was not associated with the change in
      homocysteine concentration. CONCLUSIONS: Low-dose MTX treatment in RA patients
      leads to an increased plasma homocysteine level. Concomitant folate
      supplementation with either folic or folinic acid decreases the plasma
      homocysteine level and consequently protects against potential cardiovascular
      risks. No relationship was found between the change in homocysteine concentration
      and the presence or absence of the C677T mutation in the MTHFR gene. Homocysteine
      metabolism was not associated with efficacy or toxicity of MTX treatment.

PMID- 12048293
TI  - Association of HLA-DRB1*02 with osteoarthritis in a cohort of 106 patients.
AB  - OBJECTIVE: We have previously shown that the inflammatory cytokines tumour
      necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 or IL-1beta are up
      regulated in chondrocytes of patients with osteoarthritis (OA). However, the
      inflammatory responses associated with OA are of low grade and restricted. To
      investigate the involvement of the immune system in the pathogenesis of OA, we
      analysed patients for their HLA-DRB1 haplotypes. METHODS: Combining single
      stranded oligo or sequence-specific primer typing procedures, 139 randomly
      selected controls and 106 OA patients were typed for their HLA-DRB1 alleles.
      RESULTS: The OA cohort showed statistically significant differences in the
      frequencies of the DR2 and DR5 alleles compared with the controls. While the
      frequency of the DR2 allele was elevated among the OA patients, the DR5 allele
      was negatively associated with the disease. The P values for differences from the
      controls were 0.0431 for DR2 and 0.0386 for DR5 and the odds ratios for the two
      alleles were 1.58 and 0.54 respectively. CONCLUSION: The association of DR2 and
      DR5 with OA hints at linkage disequilibrium between HLA-DRB1 genes and genes
      involved in the pathogenesis of OA. Alternatively, DR2 has a direct role in
      restricting immunological responses to the low-grade inflammation characteristic
      of OA.

PMID- 12048294
TI  - Usefulness of basal and pilocarpine-stimulated salivary flow in primary Sjogren's
      syndrome. Correlation with clinical, immunological and histological features.
AB  - OBJECTIVES: To examine salivary function in patients with primary Sjogren's
      syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of
      pilocarpine in a 5% solution, in order to define their clinical usefulness in the
      evaluation of xerostomia in patients with primary SS as well as to identify those
      factors related to the increase in salivary flow after pilocarpine stimulation.
      METHODS: We investigated the clinical and immunological characteristics of 60
      consecutive patients with primary SS. All patients fulfilled four or more of the
      preliminary diagnostic European criteria for SS. We measured unstimulated (basal)
      salivary flow (BSF) in all patients. In patients with BSF </=1.5 ml, stimulated
      salivary flows (SSF) were also measured after stimulation with an ophthalmic 5%
      pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also
      measured after oral administration of 50 mg anetholetrithione (ANTT) in the same
      patients. These stimulated salivary flows were measured 1, 2 and 3 h after the
      stimulus. RESULTS: Of the 60 patients, 55 were women and five men, with a mean
      age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was
      1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The
      stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57
      in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group
      and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the
      pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or
      immunological differences were found between SS patients with BSF more or less
      than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid
      scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with
      a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3
      months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%,
      P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV
      (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001).
      CONCLUSION: The study of xerostomia using basal and pilocarpine SSF is simple to
      perform, acceptable to patients and needs no special equipment. We describe a
      significant increase in SSF using a solution of 5% pilocarpine in comparison with
      salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients
      with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed
      a shorter duration of sicca symptoms, a lower frequency of positive immunological
      markers and milder grades of scintigraphic patterns and lymphocytic infiltrates
      in salivary gland biopsies. This subset of patients probably maintain a residual
      capacity of their salivary glands, as opposed to the 'non-responder' patients,
      who had a longer duration of sicca syndrome evolution with more severe
      involvement of the salivary glands.

PMID- 12048295
TI  - The impact of coexisting connective tissue disease on survival in patients with
      fibrosing alveolitis.
AB  - OBJECTIVES: Previous reports have suggested that patients who have fibrosing
      alveolitis in association with a connective tissue disease (FA-CTD) have a better
      prognosis than patients with 'lone' cryptogenic fibrosing alveolitis (LCFA). The
      present study was designed to compare the survival of a general population-based
      sample of patients with FA-CTD and LCFA both with each other and with the general
      population. METHODS: A survival analysis was performed using data for 107
      patients with FA-CTD, 872 with LCFA and 5958 controls matched for age, sex and
      general practice, drawn from the General Practice Research Database. The data
      were analysed using Cox regression, adjusting for a number of potential
      confounders, including age, gender, smoking habit and use of oral
      corticosteroids. RESULTS: The median follow-up period was 2.1 yr and during this
      time 54 (50%) patients with FA-CFA, 386 (44%) patients with LCFA and 601 (10%)
      controls died. The mortality rates for patients with FA-CTD, LCFA and the
      controls were 284, 270 and 41 per 1000 person-yr respectively. After adjusting
      for age, gender, smoking habit and exposure to oral corticosteroids, patients
      with FA-CTD had a marginally worse survival than patients with LCFA (hazard ratio
      1.20, 95% confidence interval 0.90-1.61). Compared with the general population
      controls, patients with either LCFA or FA-CTD had a considerably worse prognosis
      (hazard ratio 5.56, 95% confidence interval 4.77-6.49). CONCLUSIONS: The median
      survival in patients with fibrosing alveolitis is less then 3 yr. We found no
      evidence to support previous reports of a better prognosis amongst patients with
      FA-CTD.

PMID- 12048296
TI  - Consultant rheumatology workforce in the UK: changing patterns of provision 1997
      2001.
AB  - OBJECTIVES: To summarize the changes in rheumatology provision and working
      practice that have occurred on the basis of the results of the 1997, 1999 and
      2001 surveys carried out to update the British Society for Rheumatology/Arthritis
      Research Campaign Rheumatology Workforce Register. METHODS: The Workforce
      Register includes all consultant rheumatologists in the UK who do at least one
      NHS clinical session per week. Questionnaires were sent to all consultants on the
      register at the beginning of 1997, 1999 and 2001. The questionnaires asked about
      clinical commitments and workload. RESULTS: The response rates for 1997, 1999 and
      2001 surveys were 85, 86 and 92% respectively. Scotland, Wales and Northern
      Ireland all had fewer consultant rheumatologists per capita than any English
      region. Within England, the London region had 60% more rheumatologists per capita
      than any other English region. CONCLUSION: There are ongoing inequalities in the
      provision of rheumatology, especially between London and Scotland, Wales and
      Northern Ireland.

PMID- 12048297
TI  - When typical is atypical: mycobacterial infection mimicking cutaneous vasculitis.
AB  - Patients with systemic lupus erythematosus (SLE) who present with skin disease
      pose the clinician with diagnostic challenges. The skin disease can reflect an
      increase in systemic disease activity suggested by other features of active lupus
      and, as such, usually responds well to more aggressive immunosuppressive therapy.
      Other possibilities of skin disease include drug eruptions, skin disease
      unrelated to SLE and, more rarely, opportunistic skin infection. In patients who
      show a poor response to more aggressive immunosuppressive therapy, consideration
      must be given to the possibility of opportunistic infection. A high index of
      suspicion will allow prompt treatment. We describe two patients with SLE who
      developed cutaneous atypical mycobacterial infection during immunosuppressive
      therapy. The diagnosis of cutaneous vasculitis was considered in both cases, but
      subsequent skin biopsy revealed the correct diagnosis. This report illustrates
      the importance of skin biopsy in patients with suspected cutaneous lupus who are
      not responding to immunosuppressive therapy.

PMID- 12048298
TI  - Serum and synovial fluid concentration of vascular endothelial growth factor in
      juvenile idiopathic arthritides.
AB  - OBJECTIVE: To evaluate the role of vascular endothelial growth factor (VEGF) in
      the pathogenesis of local joint inflammation in juvenile idiopathic arthritis
      (JIA). METHODS: Sera from 50 patients affected with JIA and 10 age-matched
      healthy controls were tested with a commercial ELISA for VEGF. Corresponding
      synovial fluid (SF) concentrations of VEGF and p75 soluble tumour necrosis factor
      receptor (sTNFR) were evaluated in 20 active JIA patients. RESULTS: Serum
      concentrations of VEGF were significantly higher in patients with active
      polyarticular disease than in patients with active and inactive oligoarticular
      disease and healthy controls. In JIA patients, serum concentrations of VEGF
      displayed a significant correlation with a number of clinical and laboratory
      parameters of disease activity. VEGF concentrations in SF were significantly
      higher than those detected in corresponding sera. Moreover, a clear correlation
      was found between corresponding SF and serum VEGF concentrations. In SF, VEGF
      showed a strong positive correlation with p75 sTNFR. CONCLUSIONS: Concentrations
      of VEGF in SF in patients with JIA are higher than corresponding serum
      concentrations, suggesting that this pro-angiogenic factor may have a major role
      in the outgrowth of hyperplastic pannus and tissue damage at the site of tissue
      inflammation.

PMID- 12048299
TI  - Antiphospholipid syndrome in an eight-month-old infant with sickle cell trait.

PMID- 12048300
TI  - Juvenile dermatomyositis and Sjogren's syndrome occurring concurrently in an
      adolescent male.

PMID- 12048301
TI  - Re: Chehata et al. Mortality in rheumatoid arthritis: relationship to single and
      composite measures of disease activity.

PMID- 12048302
TI  - Carpal tunnel syndrome secondary to uraemic tumoral calcinosis.

PMID- 12048303
TI  - Lethal medium-vessel panarteritis mimicking deep sepsis following etanercept and
      minocycline therapy in a patient with severe rheumatoid arthritis.

PMID- 12048304
TI  - Rheumatoid corneal melt.

PMID- 12048305
TI  - The measurement of serum salivary isoamylase as a clinical parameter in Sjogren's
      syndrome.

PMID- 12048306
TI  - Renal microaneurysms in three cases of hepatitis C virus-related vasculitis.

PMID- 12048307
TI  - Rheumatology telephone helpline services.

PMID- 12048308
TI  - Tc-DTPA clearance and rheumatoid arthritis-associated fibrosing alveolitis.

PMID- 12048314
TI  - Coronary heart disease risk between active and inactive women with multiple
      sclerosis.
AB  - PURPOSE: Physical activity is strongly recommended as a principal component of
      coronary heart disease (CHD) risk factor management aimed at favorably lowering
      abdominal fat accumulation, lowering levels of triglyceride (TG), raising levels
      of high-density lipoprotein-cholesterol (HDL-C), and improving insulin
      sensitivity. Although physical activity practices are reported to be low in women
      with multiple sclerosis (MS), some women with MS remain physically active despite
      their disability. Thus, the primary aim of the study was to determine whether
      abdominal fat accumulation and levels of TG, HDL-C, and glucose differ between
      active and inactive women with MS. METHODS: The study sample consisted of 123
      women with MS, aged 23-72 yr. Venous blood was collected for measurement of
      lipids, lipoprotein-cholesterol, and glucose. Skin-fold thicknesses and girth
      circumferences were obtained for estimation of total and abdominal body fat.
      Leisure-time physical activity (LTPA) during the last 12 months was assessed by
      the physical activity questionnaire used in the Postmenopausal
      Estrogens/Progestins Intervention (PEPI) Study. Eating habits were assessed by
      the Block Food Frequency Questionnaire. RESULTS: LTPA was significantly
      associated with lower waist circumference (P = 0.0001), lower TG levels (P =
      0.0005), and lower glucose levels (0.002). After adjusting for several
      covariates, women participating in low- to moderate-intensity LTPA had
      significantly lower waist circumferences, TG levels, and glucose levels relative
      to inactive women. CONCLUSION: Low- to moderate-intensity LTPA was significantly
      associated with less abdominal fat accumulation, lower levels of TG, and lower
      levels of glucose in the present sample of women with MS. These findings suggest
      that exercise levels attainable by women with MS may improve CHD risk and
      contribute to important health-related benefits.

PMID- 12048315
TI  - Physical activity and colon cancer: confounding or interaction?
AB  - PURPOSE: Although physical activity has been consistently inversely associated
      with colon cancer incidence, the association of physical activity with other diet
      and lifestyle factors that may influence this association is less well
      understood. Confounding and effect modification are examined to better understand
      the physical activity and colon cancer association. METHODS: Based on
      hypothesized biological mechanisms whereby physical activity may alter risk of
      colon cancer, we evaluated confounding and effect modification using data
      collected as part of a case-control study of colon cancer (N = 1993 cases and
      2410 controls). We examined associations between total energy intake, fiber,
      calcium, fruit and vegetables, red meat, whole grains as well as dietary patterns
      along with cigarette smoking, alcohol consumption, BMI, and use of aspirin and/or
      NSAIDs and physical activity. RESULTS: No confounding was observed for the
      physical activity and colon cancer association. However, differences in effects
      of diet and lifestyle factors were identified depending on level of physical
      activity. Most striking were statistically significant interactions between
      physical activity and high-risk dietary pattern and vegetable intake, in that the
      relative importance of diet was dependent on level of physical activity. The
      predictive model of colon cancer risk was improved by using an interaction term
      for physical activity and other variables, including BMI, cigarette smoking,
      energy intake, dietary fiber, dietary calcium, glycemic index, lutein, folate,
      vegetable intake, and high-risk diet rather than using models that included these
      variables as independent predictors with physical activity. In populations where
      activity levels are high, the estimate of risk associated with high vegetable
      intake was 0.9 (95% CI 0.6-1.3), whereas in more sedentary populations the
      estimate of risk associated with high vegetable intake was 0.6 (95% CI 0.5-0.9).
      CONCLUSIONS: Physical activity plays an important role in the etiology of colon
      cancer. Its significance is seen by its consistent association as an independent
      predictor of colon cancer as well as by its impact on the odds ratios associated
      with other factors. Given these observations, it is most probable that physical
      activity operates through multiple biological mechanisms that influence the
      carcinogenic process.

PMID- 12048317
TI  - Effects of exercise training on cardiovagal and sympathetic responses to
      Valsalva's maneuver.
AB  - PURPOSE: We tested the hypothesis that a strictly-controlled program of aerobic
      conditioning would increase vagal and decrease sympathetic responses to Valsalva
      straining. METHODS: Eleven young men performed a maximal aerobic capacity test,
      controlled frequency breathing (0.25 Hz), and three Valsalva maneuvers before and
      after 4 wk of exercise training on a cycle ergometer (30 min at > or = 70% max
      heart rate, 3 sessions. week-1). During controlled breathing and Valsalva
      straining, we recorded the electrocardiogram, noninvasive beat-by-beat arterial
      pressure, and peroneal nerve muscle sympathetic traffic at the popliteal fossa
      (pre- and postexercise sympathetic recordings were obtainable in 7 of 11
      subjects). Vagal-cardiac tone was estimated from R-R interval standard deviations
      during controlled frequency breathing. Cardiovagal baroreflex sensitivity was
      derived from increases of R-R intervals as functions of increases in systolic
      pressures with linear regression analysis during phase IV pressure increases, and
      sympathetic sensitivity was derived from the quotient of total muscle sympathetic
      nerve activity and diastolic pressure changes during phase II pressure
      reductions. RESULTS: Exercise training increased VO2 max (3.38 +/- 0.10 pre-, and
      3.64 +/- 0.11 L. min-1 postexercise; mean +/- SE; P = 0.04), R-R interval
      standard deviations (75 +/- 0.12 pre- and 94 +/- 0.14 ms postexercise; mean +/-
      SE; P = 0.03), and cardiovagal baroreflex sensitivity (15.0 +/- 1.1 pre-, and
      25.0 ms. mm Hg-1 +/- 4.0 postexercise; mean +/- SE; P = 0.03). Exercise training
      did not change baseline sympathetic traffic (P = 0.31) or sympathetic nerve
      responses to diastolic pressure reductions (P = 0.12). CONCLUSIONS: Exercise
      training affects vagal and sympathetic mechanisms differently: cardiovagal
      baroreflex sensitivity is increased, but sympathetic responses to arterial
      pressure decreases are unchanged.

PMID- 12048316
TI  - Muscle damage and soreness after endurance exercise of the elbow flexors.
AB  - PURPOSE: This study investigated changes in indirect markers of muscle damage
      after endurance exercise of the elbow flexors and compared the changes with those
      after maximal eccentric actions (Max-ECC) of the elbow flexors. METHODS: Eighteen
      male students rhythmically lifted (1 s) and lowered (1 s) a light dumbbell (1.1
      1.8 kg: 9% of MIF) in 60-180 degrees of elbow joint angle for 2 h (2-h Ex).
      Maximal isometric force (MIF), relaxed (RANG) and flexed elbow joint angles
      (FANG), upper-arm circumference (CIR), muscle soreness (SOR), B-mode ultrasound
      (US), and plasma creatine kinase (CK) activity were assessed before and
      immediately after, and up to 96 h after exercise. RESULTS: All measures were
      altered significantly (P < 0.05) after 2-h Ex in a similar time course to Max
      ECC; however, changes in RANG, FANG, CIR, US, and CK (peak: 356 +/- 121 IU.L-1)
      were significantly (P < 0.05) smaller compared with those after Max-ECC. SOR
      developed immediately after 2-h Ex and peaked 24-48 h after exercise. MIF dropped
      to 44.1% of the preexercise level, which was significantly (P < 0.05) lower than
      that after Max-ECC (58.1%), immediately postexercise. MIF recovered to 79.8% at
      24 h, and 97.8% at 96 h postexercise, which was a significantly (P < 0.05) faster
      recovery compared with that of Max-ECC (73.1% at 96 h). CONCLUSION: These results
      showed low-intensity continuous muscle contractions (3600 times) resulted in
      muscle damage; however, the magnitude of the muscle damage was less severe, and
      the recovery was faster compared with 12 maximal eccentric muscle actions.

PMID- 12048318
TI  - Unaltered insulin sensitivity after resistance exercise bout by postmenopausal
      women.
AB  - PURPOSE: The major aims of this study were to determine whether a single session
      of resistance exercise would alter insulin sensitivity, glucose effectiveness,
      and C-peptide response to glucose challenge in a group of previously sedentary,
      postmenopausal women. METHODS: Ten postmenopausal women (aged 57.5 +/- 1.6 yr)
      were studied. Each participant underwent two frequently sampled intravenous
      glucose tolerance tests (FSIVGTT): without prior exercise (no exercise), and
      postexercise (15 h after a session of resistance exercise: three sets of 10
      repetitions performed at 50%, 75%, and 100% of 10-repetition maximum for 7
      exercises). Insulin sensitivity and glucose effectiveness were determined
      according to Bergman's minimal model procedure. In addition, C-peptide
      concentration and glucose disappearance were measured. RESULTS: There was no
      significant difference between trials for insulin sensitivity, glucose
      effectiveness, glucose disappearance, or area under the curve (AUC) for glucose
      or insulin during the glucose challenge. AUC for C-peptide tended (P = 0.059) to
      be 10% higher in the postexercise versus no exercise trial, and C-peptide values
      were significantly (P < or = 0.02) higher at several time points (60, 70, 140,
      and 180 min) during the postexercise compared with no exercise trial.
      CONCLUSIONS: In contrast to previously reported results with young men and women
      after a single bout of endurance exercise, insulin sensitivity was unaltered by a
      single session of resistance exercise in postmenopausal women. Higher plasma C
      peptide values concomitant with unchanged insulin values provide evidence that
      resistance exercise may have induced a slightly higher insulin secretion and a
      proportional increase in insulin clearance.

PMID- 12048319
TI  - The effect of mouthguard design on stresses in the tooth-bone complex.
AB  - PURPOSE: Mouthguards protect the tooth-bone complex from impact loads that occur
      during sporting activity. The aim of this study is to investigate the effects of
      varying mouthguard thickness and stiffness on the magnitude of tensile stresses
      in the tooth-bone-complex. METHODS: A two-dimensional, plane stress, finite
      element representation of a central maxillary incisor (CMI) is created. For
      validation purposes, displacements of the incisal edge of the unprotected tooth
      model are compared with in vivo displacements under similar loads. A protective
      mouthguard is then superimposed over the model with varied labial thickness (1-6
      mm) and stiffness (9-900MPa) representing a range of designs available. A large
      horizontal static load of 500N is then applied to the anterior surface of the
      mouthguard and the resulting stresses in the tooth-bone complex are presented. It
      is suggested that this loading condition most accurately represent the situation
      occurring when a guarded tooth collides with a soft object (e.g. boxing glove).
      RESULTS: It is generally found that mouthguard thickness and stiffness are both
      desirable in terms of reducing stresses. However, the protection offered by the
      low-stiffness guards, regardless of thickness, is minimal. Since this low
      stiffness (9MPa) is representative of the most common choice of material in
      mouthguard fabrication, such findings may cast doubt on the ability of popular
      mouthguards to redistribute stress. CONCLUSION: While few would disagree that
      these low-stiffness guards absorb shock during hard-object collisions (e.g.
      baseballs), they may not protect the tooth-bone during soft-object collisions
      (e.g. boxing gloves). In order to optimize their protective capabilities for a
      range of loads, the range of materials used in mouthguard construction may have
      to be reconsidered.

PMID- 12048320
TI  - Myocardial perfusion and perfusion reserve in endurance-trained men.
AB  - PURPOSE: This study was undertaken to determine whether endurance training is
      associated with changes in myocardial perfusion in humans. METHODS: Myocardial
      perfusion was measured in eleven trained and nine sedentary men at rest and
      during adenosine-stimulated hyperemia using positron emission tomography (PET).
      Left ventricular (LV) dimensions and mass were measured using echocardiography.
      Myocardial work per gram of tissue was calculated as (cardiac output. mean
      arterial blood pressure)/LV mass. RESULTS: LV mass was significantly higher and
      myocardial work per gram of tissue lower in the trained than in the untrained
      subjects. Basal (0.78 +/- 0.10 and 0.76 +/- 0.15 mL. min-1. g-1, P = NS) and
      adenosine-stimulated perfusion (3.46 +/- 0.91 and 3.14 +/- 0.70 mL. min-1. g-1, P
      = NS) were similar between trained and untrained men, respectively. Consequently,
      myocardial perfusion reserve was similar in both groups (4.4 +/- 1.2 and 4.1 +/-
      0.7, P = NS). In addition, coronary resistance at baseline (115 +/- 17 vs 119 +/-
      22, mm Hg. mL. min-1. g-1, P = NS) and during adenosine infusion (28 +/- 8 vs 30
      +/- 8, mm Hg. mL. min-1. g-1, P = NS) were similar in both groups. Resting
      myocardial work correlated with resting myocardial perfusion in both groups, but
      the relationship between perfusion and work was different between the groups so
      that perfusion for a given myocardial work was significantly higher in trained
      subjects (0.56 +/- 0.04 and 0.34 +/- 0.05 mL. (mm Hg. L)-1, P < 0.001).
      CONCLUSIONS: These findings suggest that endurance trained subjects do not have
      different resting or adenosine-stimulated myocardial perfusion. However, the
      relationship between myocardial perfusion and work appears altered in the
      athletes.

PMID- 12048321
TI  - Circulating white blood cells affect red cell pulmonary transit times in
      endurance athletes during intense exercise.
AB  - PURPOSE: The aim of this study was to determine the relationship between the
      right-to-left ventricular red cell pulmonary transit times (PTT) during intense
      exercise and circulating white blood cell (WBC) counts in highly trained
      endurance athletes. We postulated that high levels of WBCs preexercise would slow
      PTT. Eleven endurance-trained athletes (VO2max = 69.6 +/- 7.7 mL.kg-1.min-1;
      weight = 75.0 +/- 6.2 kg; height = 181.0 +/- 7.1 cm) performed 6.5 min constant
      load, near-maximal cycling exercise (approximately 92% VO2max) on two different
      days. Preexercise WBC counts were measured in arterial blood drawn from the
      radial artery 30 min before exercise. PTT was measured during the 3rd min of
      exercise by first-pass radionuclide cardiography using centroid and deconvolution
      analysis, whereas cardiac output (Q) was measured during the last 2.5 min of
      exercise via a count-based ratio method from the MUGA technique. RESULTS:
      Combined mean PTT from both deconvolution and centroid analysis at minute three
      of exercise was 2.45 +/- 0.21 s, whereas the preexercise WBC count was 5.3 +/-
      1.6 x 109.L-1. Cardiopulmonary blood volume at minute three of exercise was 1.22
      +/- 0.13 L, VO2 was 4.58 +/- 0.44 L.min-1, and Q was 30.2 +/- 4.2 L.min-1. We
      found that PTT was negatively correlated with circulating WBC (r = -0.61;
      adjusted r2 = 0.30; P = 0.04; N = 11) but not with the dispersion (spread) of
      transit times around the mean (r = 0.19; P = 0.57). CONCLUSION: This suggests
      that athletes with higher circulating numbers of WBCs preexercise have faster
      (shorter) red cell transit times through the lung during intense exercise.

PMID- 12048322
TI  - Stability and reproducibility of brachial artery flow-mediated dilation.
AB  - PURPOSE: Brachial artery flow-mediated dilation (BAFMD) is a noninvasive
      technique, which has been suggested as a potential means of identifying patients
      with early atherosclerosis and therefore has enormous clinical appeal. Despite
      this, the stability and reproducibility of this technique are not yet clear.
      Therefore, the purpose of this study was to establish the stability and
      reproducibility of BAFMD after 5 min of forearm occlusion and to produce power
      calculations to aid in clinical trial design. METHODS: Twenty-six healthy
      volunteers underwent high-resolution ultrasonographic brachial artery assessments
      before, during, and after 5 min of forearm occlusion. The study design involved
      three scans on 2 d, performed by two ultrasonographers and analyzed by two
      readers. All subjects were tested between 7 and 11 a.m. after refraining from
      food and exercise. The nondominant arms were scanned, in longitudinal view,
      approximately 4 cm proximal to the olecranon process, in the anterior/medial
      plane. Blood draws were performed on each visit. The SAS MIXED restricted maximum
      likelihood (REML) procedure for an unbalanced design was used to calculate
      variance components and provide power calculations. RESULTS: Average baseline
      artery diameter for all studies was 3.48 +/- 0.53 mm. This increased to 3.71 +/-
      0.57 mm (6.58 +/- 4.15%) at peak dilation. Intraclass correlation coefficients
      (ICCC) for days, testers, and readers were 0.92, 0.94, and 0.90, respectively. To
      detect a difference in vasoreactivity of 60% (two-tailed), e.g., 5% vasodilation
      versus 8% vasodilation, at 90% power, 23 and 10 subjects would be required for
      cross-sectional and pre-post designs, respectively. CONCLUSIONS: These data
      indicate adequate stability and reproducibility of the BAFMD technique under
      controlled conditions. Additionally, BAFMD appears useful to differentiate
      between groups, although its prognostic value for the examination of individuals
      is unclear.

PMID- 12048323
TI  - High VO2max with no history of training is primarily due to high blood volume.
AB  - PURPOSE: To investigate the high VO2max observed occasionally in young men who
      have no history of training. METHODS: VO2max, blood volume (BV), maximal stroke
      volume (SVmax), maximal cardiac output (Qmax), and related measurements (reported
      as mean +/- SEM) were studied in six men (mean age 20.0 +/- 0.5 yr) with no
      history of training, who all had a VO2max below 49 mL.kg-1.min-1 (LO group) and
      six age- and weight-matched men (mean age 19.5 +/- 0.5 yr) with no history of
      training, who all had a VO2max above 62.5 mL.kg-1.min-1 (HI group). RESULTS:
      Compared with the LO group, the HI group had a higher SVmax (149 +/- 5 vs 102 +/-
      5 mL), higher Qmax (28.9 +/- 0.9 vs 20.0 +/- 1.0 L.min-1) and higher BV (88.1 +/-
      3.8 vs 76.7 +/- 0.9 mL.kg-1). The BV of four participants in the HI group (mean =
      92.3 +/- 4.3 mL.kg-1) was substantially higher than the BV of all participants in
      the LO group, but two participants in the HI group had a BV (mean = 79.7 +/- 0.8
      mL.kg-1) that was similar to the mean BV of the LO group. CONCLUSION: The primary
      explanation for the high VO2max observed occasionally in young men who have no
      history of training is a naturally occurring (perhaps genetically determined)
      high BV that brings about a high SVmax and Qmax. However, some young men with no
      history of training have a high VO2max, SVmax, and Qmax possibly because a
      greater portion of their BV is hemodynamically active.

PMID- 12048325
TI  - Rapid carbohydrate loading after a short bout of near maximal-intensity exercise.
AB  - PURPOSE: One limitation shared by all published carbohydrate-loading regimens is
      that 2-6 d are required for the attainment of supranormal muscle glycogen levels.
      Because high rates of glycogen resynthesis are reported during recovery from
      exercise of near-maximal intensity and that these rates could in theory allow
      muscle to attain supranormal glycogen levels in less than 24 h, the purpose of
      this study was to examine whether a combination of a short bout of high-intensity
      exercise with 1 d of a high-carbohydrate intake offers the basis for an improved
      carbohydrate-loading regimen. METHODS: Seven endurance-trained athletes cycled
      for 150 s at 130% VO2peak followed by 30 s of all-out cycling. During the
      following 24 h, each subject was asked to ingest 12 g.kg-1 of lean body mass (the
      equivalent of 10.3 g.kg-1 body mass) of high-carbohydrate foods with a high
      glycemic index. RESULTS: Muscle glycogen increased from preloading levels (+/-
      SE) of 109.1 +/- 8.2 to 198.2 +/- 13.1 mmol.kg-1 wet weight within only 24 h,
      these levels being comparable to or higher than those reported by others over a 2
      to 6-d regimen. Densitometric analysis of muscle sections stained with periodic
      acid-Schiff not only corroborated these findings but also indicated that after 24
      h of high-carbohydrate intake, glycogen stores reached similar levels in Type I,
      IIa, and IIb muscle fibers. CONCLUSION: This study shows that a combination of a
      short-term bout of high-intensity exercise followed by a high-carbohydrate intake
      enables athletes to attain supranormal muscle glycogen levels within only 24 h.

PMID- 12048324
TI  - Heritability of HR and BP response to exercise training in the HERITAGE Family
      Study.
AB  - PURPOSE: The heritability of the response to exercise training in resting blood
      pressure (BP) and heart rate (HR) was assessed in 482 Caucasian individuals
      comprising 98 families participating in the HERITAGE Family Study. METHODS: All
      individuals were sedentary at the baseline visit (time 1 measurement). After
      completing a 20-wk exercise-training program, subjects were measured again (time
      2). A familial correlation model was used to assess the heritability (genetic
      plus familial environmental) of the response in resting systolic BP (SBP),
      diastolic BP (DBP), and HR, computed as the difference between the two
      measurement times. This response was adjusted for the effects of baseline levels
      and age within sex and generation groups. Analyses were conducted separately in a
      subsample of families in which at least one family member was considered to have
      elevated BP (95th percentile; SBP > or = 135 or DBP > or = 80). RESULTS: Several
      novel findings emerged from this study. First, the SBP and HR response may be
      influenced by genetic factors. The maximal heritabilities were 20% (SBP) and 36%
      (HR) in the elevated BP, 18% and 24% in the complete, and not significant in the
      normotensive samples. For DBP, there were cohort effects (significant sibling and
      spouse but not parent-offspring correlations) in the complete and normotensive
      samples that may be due to generation-specific environmental influences.
      CONCLUSION: The trainability of SBP and HR in families with elevated BP appears
      to be determined in part by genetic factors, whereas DBP trainability may be more
      a function of environmental effects.

PMID- 12048326
TI  - Validity and reproducibility of a physical activity questionnaire in women.
AB  - PURPOSE: To determine the validity and reproducibility of a self-administered
      physical activity questionnaire that assesses the frequency, intensity, and
      duration of recreational, household, and occupational activity in women. METHODS:
      The questionnaire was administered by mail twice to 131 participants 1 yr apart.
      During this interval, participants completed four 1-wk activity logs
      corresponding to different seasons throughout the year. RESULTS: The intraclass
      correlation coefficients used to measure reproducibility were 0.82 for total
      activity, 0.79 for moderate activity, 0.86 for vigorous activity, 0.80 for
      recreational activity, and 0.73 for household activity. The distribution of
      activity scores was similar between the questionnaires and the average of the
      four logs, indicating the participants' ability to incorporate seasonal variation
      into their recall on a questionnaire. The correlations between the questionnaire
      based activity scores and log-based activity scores, indicating validity, were
      0.26 for total activity, 0.15 for moderate activity, and 0.52 for vigorous
      activity. Women younger than age 50 tended to have higher validity scores than
      women aged 50 yr and older (r = 0.31 vs r = 0.19, respectively, for total
      activity). CONCLUSION: These data indicate that this physical activity
      questionnaire is reproducible and provides a useful measure of current activity,
      particularly vigorous activity, over a 1-yr period.

PMID- 12048327
TI  - Injuries in competitive youth bandy: an epidemiological study of a league season.
AB  - PURPOSE: Bandy, with a century-long tradition in northern Europe, is a winter
      team-sport similar to ice hockey. To investigate the occurrence of injuries
      during competitive youth bandy games, injury incidence, injury types, and age
      related risks were analyzed for one youth league season. METHODS: The National
      Athletic Injury/Illness Reporting System (NAIRS) definition of sports injury was
      used for the injury registration. All 416 games during the 1999-2000 season in
      the Swedish southeastern youth bandy league were included in the study. Primary
      data was collected by a questionnaire and completed by the team coaches after
      each game. At the end of the season, physician interviews with each team coach
      were performed to assure that no injuries had been missed as well as to ascertain
      whether there was any remaining disability. RESULTS: In total, 2.0 injuries (95%
      confidence interval 1.2-2.9 injuries) per 1000 player game hours were recorded.
      Sixty-eight percent of the injuries caused the injured player to be absent from
      bandy play for more than a week. Collision was the most common cause of injury
      (36%), and contusion was the most common injury type (41%). The injury incidence
      in the leagues for older players (Youth 14 -Youth 16) was slightly higher than in
      the leagues for the younger players (Youth 12 -Youth 13), while participation by
      under-aged players in games organized for older players led to an almost four
      fold increase of injury risk. For severe injuries, the mean rehabilitation time
      away from bandy practice or competition was 27 d (range 8-56 d). CONCLUSION: The
      overall injury incidence during youth bandy games is low, but the injuries that
      occur cause extensive absences from the only four months long bandy season. From
      a public health perspective, bandy can be recommended for consideration when
      physical exercise is to be promoted among school-age children in countries with a
      winter climate.

PMID- 12048328
TI  - Impacts and kinematic adjustments during an exhaustive run.
AB  - PURPOSE: To examine the kinematic adjustments that runners make during an
      exhaustive run and to look at the effects these adjustments have on shock and
      shock attenuation. METHODS: Ten recreational runners ran to volitional exhaustion
      on a treadmill at a velocity equal to their average 3200-m running velocity at
      maximal effort (average time: 15.7 +/- 1.7 min). Head and leg accelerometers, a
      knee electrogoniometer, and a rearfoot electrogoniometer were attached to each
      subject. The data were sampled at 1000 Hz at the start, middle, and end of the
      run. RESULTS: The knee became significantly more flexed at heel impact (start:
      164.9 +/- 2.3 degrees; end: 160.5 +/- 2.9 degrees; P < 0.05). The rearfoot angle
      became more inverted at impact (start: 12.2 +/- 1.6 degrees; end: 13.6 +/- 1.9
      degrees; P < 0.05). These kinematic changes resulted in a lower extremity that
      that had a lower effective mass during the impact. This decreased effective mass
      allowed the leg to accelerate more easily; thus, peak leg impact accelerations
      (start: 6.11 +/- 0.96 g; end: 7.38 +/- 1.05 g; P < 0.05) and impact attenuation
      (start: 74.5 +/- 5.4%; end: 77.5 +/- 4.1%; P < 0.05) increased during the
      progression of the run. CONCLUSIONS: The increase in peak impact accelerations at
      the leg was not considered an increased injury risk because of the decreased
      effective mass. The altered kinematics may have resulted in increased metabolic
      costs during the latter stages of the exhaustive run.

PMID- 12048329
TI  - Is eccentric exercise-induced torque decrease contraction type dependent?
AB  - PURPOSE: This study was designed to determine whether torque decrease following
      an acute eccentric exercise is contraction type dependent. METHODS: Ten active
      males performed an exercise session consisting of five sets of ten maximal
      eccentric muscle actions of the elbow flexors. Before and immediately after the
      exercise, maximal voluntary eccentric (-60 degrees.s-1; Ecc60), isometric (0
      degrees.s-1; Iso) and concentric (60 degrees.s-1; Con60 and 240 degrees.s-1;
      Con240) torque were measured. In order to distinguish central from peripheral
      factors involved in torque decrement, activation level (twitch interpolation
      technique), myoelectrical activity (RMS) of biceps brachii, as well as
      electrically evoked M-wave and peak twitch torque (Pt) were recorded. RESULTS:
      The eccentric exercise induced a significant torque reduction (P < 0.01),
      whatever the muscular contraction type [mean (SD): -22.3 (8.1)% for Ecc60; -20.8
      (11.2)% for Iso; -18.5 (6.1)% for Con60 and -12.5 (8.9)% for Con240]. Relative
      torque decrement was however significantly less for Con240 compared with Ecc60,
      Iso, and Con60 (P < 0.05). Torque decreases were associated with a reduction of
      both M-wave amplitude (P < 0.01) and Pt (P < 0.001), probably related to an
      impairment of the excitation-contraction coupling. Concurrently, activation level
      was reduced (P < 0.01), therefore indicating the occurrence of central fatigue,
      as also confirmed by RMS decreases for all the conditions (P < 0.05), except
      Con240. DISCUSSION: An acute eccentric exercise induced a significant voluntary
      maximal torque reduction during eccentric, isometric, and concentric muscle
      actions ascribed to both peripheral and central failure of force production
      capacity. It can be concluded that eccentric exercise-induced torque decrease is
      not contraction type dependent.

PMID- 12048330
TI  - A dimensional paradigm for identifying the size-independent cost of walking.
AB  - PURPOSE: The purpose of this investigation was to present an alternative paradigm
      to that of dividing the rate of oxygen consumption by body mass (VO2.M-1, mL.min
      1kg-1) for comparing walking economy in humans. METHODS: The paradigm used
      dimensional analysis and similarity theory to derive a measure of size
      independent cost (SIC), defined as the net oxygen cost to move a mass of one
      kilogram a distance equal to stature. Mass-specific gross oxygen cost per
      kilometer, mass-specific net oxygen cost per kilometer, and SIC were used to
      analyze results from 184 subjects who performed level treadmill walking. Subjects
      were 63 children, 40 adolescents, 42 adults, and 39 seniors (approximately equal
      numbers of male and female subjects) walking at treadmill speeds from 0.9 to 1.8
      m.s-1. RESULTS: Comparisons of metabolic cost between children and the older
      groups were dependent on the measure of metabolic cost and speed. At each speed,
      VO2gross.M-1 was higher in children than in older groups, whereas VO2net.M-1 of
      children was higher at 1.1 and 1.3, but similar at 0.9 m.s-1. SIC of children was
      similar at 1.1 and 1.3 m.s-1 but lower than the older groups at 0.9 m.s-1.
      CONCLUSIONS: Higher mass-specific metabolic costs of children were explained by
      differences in standing metabolism and stature. When these variables were
      considered, children had similar or lower metabolic costs than older subjects.
      Alternatives to using mass alone to normalize locomotor economy are warranted.

PMID- 12048331
TI  - Minimum rest period for strength recovery during a common isokinetic testing
      protocol.
AB  - PURPOSE: The intent of this investigation was to determine the minimal time for a
      between sets rest period during a common isokinetic knee extension strength
      testing protocol. Based on a review of the literature, a set was considered a
      group of four maximal coupled contractions at a specific velocity. METHODS:
      Eleven normal, healthy college-age men underwent unilateral knee extension
      testing to determine their individual isokinetic peak torque at 60, 120, 180,
      240, and 300 degrees.s-1. Velocities were administered in ascending order.
      Between sets, rest periods of 15, 60, 180, and 300 s were assigned to subjects in
      a counterbalanced fashion. RESULTS: There were no differences in peak torque at
      the beginning velocity of 60 degrees.s-1 among any of the rest periods. At 120
      degrees.s-1, peak torque production during the 15-s rest period trial was similar
      to 60 s but lower than 180 and 300 s. Peak torques at 180, 240, and 300 degrees.s
      1 produced during the 15-s rest period test were significantly lower than
      measured torques at the same velocities during the 60, 180, and 300-s rest period
      tests (P < 0.05). There were no differences in peak torque production between the
      60, 180, and 300-s rest period tests. CONCLUSION: These data demonstrate that
      during a common isokinetic strength testing protocol a between set rest period of
      at least 60 s is sufficient for recovery before the next test set.

PMID- 12048333
TI  - The 4000-m team pursuit cycling world record: theoretical and practical aspects.
AB  - Due to constant competition conditions, track cycling can be accurately modeled
      through physiological and biomechanical means. Mathematical modeling predicts an
      average workload of 520 W for every team member for a new team pursuit world
      record. Performance in team pursuit racing is highly dependent on aerobic
      capacity, anaerobic skills, and aerodynamic factors. The training concept of the
      2000 record-breaking team pursuit team was based on unspecific training of these
      qualities and periodical, short-term recall of previously acquired track specific
      skills. Aerobic performance was trained through high overall training mileage
      (29,000-35,000 km.yr-1) with workload peaks during road stage races. Before major
      track events, anaerobic performance, and track-specific technical and motor
      skills were improved through discipline-specific track training. Training
      intensities were monitored through heart rate and lactate field tests during
      defined track-training bouts, based on previously performed laboratory exercise
      tests. During pursuit competition, analysis of half-lap split times allowed an
      estimation of the individual contribution of each rider to the team's performance
      and thereby facilitated modifications in team composition to optimize race speed.
      The theoretically predicted performance necessary for a new world record was
      achieved through careful planning of training and competition schedules based on
      a concise theoretical concept and the high physiological capacities of the
      participating athletes.

PMID- 12048332
TI  - Resistance training and intra-abdominal adipose tissue in older men and women.
AB  - PURPOSE: Little is known concerning the effects of resistance-exercise training
      (RT) on older adult's intra-abdominal adipose tissue (IAAT). The purpose of this
      study was to determine the effects of RT on fat distribution in 12 women and 14
      men, aged 61-77 yr. METHODS: Computed tomography IAAT and abdominal subcutaneous
      adipose tissue (SAT), densitometry-determined body composition, one-repetition
      maximum (1-RM), and isometric strength were measured before and after 25 wk of
      RT. Training consisted of two sets of 10 repetitions at 65-80% of 1-RM, three
      times each week. RESULTS: There were similar increases in strength for both the
      men and women. Women improved 22% and 38% in the isometric strength test and 1-RM
      test, respectively, whereas the men improved 21% and 36%, respectively. A
      significant increase in fat-free mass (FFM) was found for both men and women.
      However, there was a significant gender x time interaction, which indicated that
      men increased FFM more than women (2.8 kg vs 1.0 kg, respectively). Similar
      decreases in fat mass (FM) were found for the men (1.8 kg) and women (1.7 kg).
      However, women lost a significant amount of IAAT (131 to 116 cm2), whereas the
      men did not (143 to 152 cm2). Similarly, women also lost a significant amount of
      SAT (254 to 239 cm2), but men did not (165 to 165 cm2). CONCLUSION: Despite
      similar decreases in FM after a 25-wk RT program, older women lost significant
      amounts of IAAT and SAT, whereas the older men did not.

PMID- 12048334
TI  - Handgrip contribution to lactate production and leg power during high-intensity
      exercise.
AB  - PURPOSE: The purpose of this study was to examine the upper-body contribution via
      handgrip to power profiles and blood lactate concentrations during high-intensity
      cycle ergometry. METHODS: Nine trained male subjects each completed a 20-s high
      intensity cycle ergometer test twice, in a random manner, using two protocols,
      with a handgrip (WG), and without handgrip (WOHG). Capillary (earlobe) blood
      samples were obtained pre- and post-exercise. Blood samples were corrected for
      plasma volume changes and analyzed to determine blood lactate concentrations.
      RESULTS: In the WG protocol, mean (+/-SEM) blood lactate concentrations sampled
      over the three conditions were 0.98 +/- 0.33 mmol.L-1, 5.68 +/- 0.46 mmol.L-1,
      and 9.14 +/- 0.38 mmol.L-1, respectively. During the WOHG protocol, blood lactate
      values recorded were 0.99 +/- 0.26 mmol.L-1, 5.58 +/- 0.58 mmol.L-1, and 7.62 +/-
      0.65 mmol.L-1, respectively. Differences were found (P < 0.05) from rest to 4 min
      after exercise for both groups. Differences in concentrations were also observed
      between groups at the 4-min postexercise blood-sampling stage. Peak power output
      values recorded using the WG protocol were also greater (1461 +/- 94 W vs 1136 +/
      88 W; P < 0.05). No differences were recorded for mean power output (MPO),
      fatigue index (FI), or work done (WD). CONCLUSION: Results indicate significant
      differences in power output and blood lactate concentrations between protocols.
      These findings suggest that the performance of traditional style leg-cycle
      ergometry requires a muscular contribution from the whole body. As such,
      researchers should consider this, both in terms of the allocation of ergometer
      loads, and in the analysis of blood-borne metabolites.

PMID- 12048335
TI  - The influence of pacing strategy on VO2 and supramaximal kayak performance.
AB  - PURPOSE: The purpose of this study was to investigate the effects of manipulating
      pacing strategy on VO2 and kayak ergometer performance in well-trained paddlers.
      METHODS: Eight well-trained kayak paddlers (500-m time = 115-125 s) first
      performed a graded exercise test for determination of VO2max and lactate (La-)
      parameters. On subsequent days and in a random, counterbalanced order, subjects
      performed a 2-min, kayak ergometer test using either an all-out start or even
      pacing strategy. RESULTS: There was a significantly greater peak power (747.6 +/-
      152.0 vs 558.3 +/- 110.1 W) and average power (348.5 +/- 47.6 vs 335.5 +/- 44.8
      W) using the all-out start strategy, when compared with the even-paced strategy.
      There was however, no significant difference between the two pacing strategies
      for peak VO2, accumulated oxygen deficit (AOD), peak [La-], or posttest pH. Using
      the all-out start, total VO2 was significantly greater (7.3 +/- 0.8 vs 6.9 +/-
      0.8 L). CONCLUSION: The results of this study indicate that 2-min kayak ergometer
      performance is significantly greater following an all-out start strategy when
      compared with an even-paced strategy. The improved performance appears to be
      attributable to faster VO2 kinetics, without a significant change in the total
      AOD (although the AOD distribution was altered).

PMID- 12048336
TI  - Total energy expenditure during arduous wildfire suppression.
AB  - PURPOSE: The purpose of this investigation was to determine the total energy
      expenditure (TEE) by using the doubly labeled water (DLW) methodology during 5 d
      of wildfire suppression in Montana, California, Florida, Washington, and Idaho.
      METHODS: Seventeen wildland firefighters (from three Interagency Hot Shot crews,
      N = 8 men, height = 177 +/- 7 cm, weight = 74.6 +/- 6.4 kg, age = 24.5 +/- 1.8
      yr; N = 9 women, height = 170 +/- 7 cm, weight = 65.2 +/- 8.0 kg, age = 25.0 +/-
      1.3 yr) served as subjects. Before wildland fire suppression, each subject was
      given an oral dose of 2H2O and H218O (approximately 0.23 g 2H2O.kg estimated TBW
      1 and 0.39 g H218O.kg estimated TBW-1). Urine samples were collected between 0400
      and 0600 daily. TEE was calculated using the two-point method for days 1-3 and 1
      5, with the TEE for days 4-5 calculated by extrapolation. Urine samples from
      other crew members not participating in the DLW protocol were collected at the
      same times and used to adjust calculations of isotopic elimination for background
      shifts. RESULTS: TEE was 17.4 +/- 3.7 and 17.5 +/- 6.9 MJ.d-1 during days 1-3 and
      4-5, respectively. The energy expenditure associated with physical activity (EEA)
      was 8.8 +/- 3.0 and 8.9 +/- 6.1 MJ.d-1 for days 1-3 and 4-5, respectively.
      CONCLUSION: The current data demonstrate consistently high daily energy
      expenditure in the wildland firefighter. These data also demonstrate that the
      doubly labeled water methodology is an appropriate methodology for the measure of
      TEE during unpredictable field operations if adjustments are made for changes in
      background enrichment and elevated water turnover.

PMID- 12048338
TI  - Measuring success in case management.

PMID- 12048339
TI  - Strengthening patient-provider relationships.
AB  - In support of the Veterans Health Administration commitment to the promotion of
      shared decision-making between providers and patients, this study investigated
      the relationship between the provision of a patient appointment guidebook,
      designed to promote and support patient participation in the health care visit,
      and patient perceptions of primary care visit effectiveness. This study compared
      perceptions among 277 randomly selected patients randomly assigned to one of two
      groups. Patients assigned to an intervention group received a patient appointment
      guidebook along with the standard appointment reminder letter prior to the
      scheduled routine visit. Patients assigned to a control group received only the
      standard appointment reminder letter. Patient perceptions were assessed with a
      follow-up questionnaire designed to measure patient agreement with six statements
      pertaining to primary care visit effectiveness. No significant differences were
      noted in the proportion of patients in the two groups that agreed with any of the
      six statements pertaining to primary care visit effectiveness. Significant
      differences were noted, however, in the proportion of patients in the groups who
      received preventive health care interventions of influenza vaccination,
      pneumococcal vaccination, and gender-specific cancer screening. Approximately 37%
      of the patients in the intervention group provided positive comments about the
      patient appointment guidebook, while only 7% provided negative comments. Although
      statistically inconclusive, the narrative comments indicate that a patient
      appointment guidebook may assist veterans in preparing for primary care
      appointments. The lack of significant difference between the two groups on the
      measures of primary care visit effectiveness may be due, in part, to positive
      perceptions among the sample in general, as reflected by high levels of agreement
      and predominantly positive comments for both control and intervention groups.

PMID- 12048341
TI  - Using a physician-aligned case management model to influence hospital length of
      stay and payer denials.
AB  - The need for physician-hospital alignment is increasingly important with evolving
      managed care relationships among physicians, health plans, and hospitals. A 310
      bed community hospital implemented a physician-centric case management model in
      October 1999 due to the increasing pressure from managed care to lower hospital
      lengths of stay, payer denial rates, and overall costs. The medical-surgical
      inpatient population was chosen as the study group for examining the influence of
      the new model. Comparative data on average length of stay and payer denied days
      were reviewed pre- and postimplementation of the new model. The analyzed results
      showed a decrease in the number of payer-denied days by nearly one third with a
      relatively stable average length of stay.

PMID- 12048340
TI  - Improving pregnancy outcome and reducing avoidable clinical resource utilization
      through telephonic perinatal care coordination.
AB  - The effects of telephonic nursing case management and standard care in a low
      income, high-risk pregnancy population, controlling for gestational age at
      referral and risk factors (medical, demographic, and behavioral) were compared.
      The hypothesis was that a program of telephonic perinatal nursing care
      coordination and case management would increase mean gestational ages and mean
      birth weights and would reduce clinical resource utilization, compared with
      standard nursing care. The methods focused on a telephonic model developed during
      the past 16 years that included risk assessment, patient education, coordination
      of care for home services and clinic appointments, coordination of interventions
      requested by care providers, and patient advocacy. The patient population,
      primarily of minority cultural and racial backgrounds, obtained prenatal care
      from two large obstetric clinics and delivered at a level-3 tertiary care center.
      They were randomly assigned to treatment (N = 61) and control (N = 50)
      conditions. Interpreters were used for any contacts with non-English-speaking
      patients. The results demonstrated increased mean birth weights for the treatment
      group when intervening variables were controlled. Mean gestational age at
      delivery was not significantly different between groups. Telephonic case
      management saved an average of 501.31 dollars per patient in inpatient and
      outpatient costs combined. In the treatment group, for every dollar spent on case
      management costs, the savings were 4.08 dollars.

PMID- 12048342
TI  - Emergency department case management: the dyad team of nurse case manager and
      social worker improve discharge planning and patient and staff satisfaction while
      decreasing inappropriate admissions and costs: a literature review.
AB  - A model of emergency department (ED) case management consisting of a social
      worker and a nurse case manager can prevent inappropriate admissions, improve
      discharge planning, decrease cost, and enhance patient satisfaction.3 The
      individual and combined roles of the dyad team of social worker and nurse case
      manager are discussed. A literature review includes how a case management dyad
      team of social worker and nurse case manager in the ED can decrease utilization
      of the ED for nonemergent visits, promote the use of community resources, and
      improve discharge planning to avoid excessive costs. The importance of the dyad
      team working with the interdisciplinary team in the ED, the primary care
      physician (PCP), and other community health care providers in order to provide a
      holistic approach to care is addressed. A discussion about the improvement of
      both patient and staff satisfaction demonstrates the results of case management
      strategies that support and advocate for patients to receive quality, cost
      effective care across the health care continuum, while decreasing the use of the
      ED for nonemergent care.

PMID- 12048343
TI  - An empowerment model for social welfare consumers: its effectiveness and
      implications for welfare reform.
AB  - There is no uniformly accepted social work case management treatment model for
      use with impoverished consumers of social welfare services. Differences in
      intervention models vary greatly across the spectrum of social welfare agencies.
      There is even marked variance among providers within these agencies. This article
      summarizes the results of a study of the effects of an empowerment model with
      public welfare consumers based upon task-centered case management practice. The
      results of this intervention were assessed over a period of 7 months using ten
      professional social workers and a sample of 174 public social welfare consumers.
      The basic research design was a two-group field experiment. Community adjustment
      was conceptualized and operationalized along eight problem areas. Repeated
      measures, multivariate analysis of variance identified improvement in six of
      eight areas of community adjustment when the task-centered case management model
      was implemented. Given both time parameters and required outcomes of the efficacy
      of welfare reform under the 1996 Personal Responsibility and Work Opportunity
      Reconciliation Act, the task-centered model facilitates rapid involvement of
      public welfare consumers with a systematic, outcome-oriented process.

PMID- 12048344
TI  - Interleukin-18 as a novel, distinct, and distant member of the interleukin-1
      family promoting development of the adaptive immune response: the interleukin-18
      issue of the Journal of Immunotherapy.

PMID- 12048345
TI  - Roles of interleukin-18 in tissue destruction and compensatory reactions.
AB  - Interleukin (IL)-18 is a member of the IL-1 cytokine family. Pro-IL-18 is cleaved
      by caspase-1 (IL-1beta-converting enzyme) to yield biologically active 18-kDa IL
      18. Interleukin-18 is recognized by a heterodimeric receptor, consisting of a
      ligand-binding alpha-chain (IL-18Ralpha/IL-1Rrp) and an associating beta-chain
      (IL-18Rbeta/AcPL), which transmits signals through MyD88/IRAK/TRAF-6 molecules.
      Interleukin-18 is expressed in various types of cells, including macrophages,
      keratinocytes, intestinal epitherial cells, osteoblastic cells, chondrocytes, and
      adrenal cortex cells. Interleukin-18 promotes IFN-gamma production and Th1 helper
      T-cell development, synergistically with IL-12. However, IL-18 itself shows
      capabilities to induce IL-4, IL-5, IL-10, and IL-13 from T and natural killer
      cells. It also induces PGE2 production from activated macrophages. Moreover, many
      diseases are characterized by the production of IL-18 in the lesion. Taking these
      data together, our working hypothesis on how IL-18 is involved in "destructive"
      and "compensatory" pathways is proposed in this issue.

PMID- 12048346
TI  - Interleukin-18 and host defense against infectious pathogens.
AB  - Host defense to infectious pathogens is largely mediated by neutrophil-,
      cellular, or humoral immunity or eosinophil-dependent mechanism. Each mechanism
      preferentially acts against extracellular or intracellular microbial pathogens,
      viruses, or helminthes. These host defense responses are strictly regulated by
      two different categories of cytokines, T helper (Th)1 and Th2 cytokines.
      Interleukin-18, originally found as interferon-gamma-inducing factor, has now
      been identified to be involved in the development of Th1 and Th2 cells, which
      suggests the considerable involvement of this cytokine in the protective immune
      responses against infection. This review focuses on the role of interleukin-18 in
      the development and regulation of host resistance to infectious pathogens, with
      an emphasis on the infection with Cryptococcus neoformans, an intracellular
      fungal pathogen, as determined by recent studies from our laboratory.

PMID- 12048347
TI  - High-dose recombinant interleukin-18 induces an effective Th1 immune response to
      murine MOPC-315 plasmacytoma.
AB  - Interleukin (IL)-18 has profound antitumor activity when administered at high
      doses as a single agent for prolonged periods in BALB/c mice bearing late, well
      established MOPC-315 tumors. Management with a qD x 27 schedule resulted in
      regression of tumors in all animals receiving 5 mg/kg/d. A protracted daily
      management regimen appears to be necessary to induce regression in this advanced
      tumor model. Biologic markers were assessed and appear to be potentially useful
      in evaluating the immunologic and antitumor activity of IL-18. The biomarkers of
      IL-18's immunologic activity include, but are not limited to, IL-1alpha, IL-2, IL
      8, IL-10, IL-12, IL-13, interferon-gamma, tumor necrosis factor-alpha, and
      granulocyte-macrophage colony-stimulating factor. The profile of these
      circulating cytokines and their expression levels at baseline, and after IL-18
      delivery, can be measured in the serum, as well as from splenocytes of mice or
      human peripheral blood mononuclear cells derived from either normal subjects or
      patients with cancer. We compared IL-18 and IL-12 alone or in combination for
      their ability to induce cytokine production and natural killer cytolytic
      activity. Our data support the notion that IL-18 induces a predominantly Th1
      response, and that the mechanism of IL-18 activity differs from that of IL-12.
      The biologic activity of IL-18 management revealed by increases in serum levels
      of cytokines and enhancement of natural killer cytolytic activity will be useful
      as clinical trials initiate in 2002. Expression of interferon-gamma and
      granulocyte-macrophage colony-stimulating factor serum levels correlates directly
      over a broad dose escalation with the level of IL-18. Therefore, this provides a
      convenient pharmacodynamic reference to the biologic response to IL-18 that may
      serve to guide the conduct of clinical trials.

PMID- 12048348
TI  - Antitumor activity of interleukin-18 against the murine T-cell leukemia/lymphoma
      EL-4 in syngeneic mice.
AB  - Interleukin (IL)-18 induces interferon (IFN)-gamma production by T cells and
      natural killer (NK) cells, and augments NK cell activity in mouse spleen cell
      cultures. It has recently been demonstrated that in vivo administration of IL-18
      to mice results in considerable antitumor effects against syngeneic Meth A
      sarcoma. In this study, the antitumor effects of IL-18 against murine T-cell
      leukemia (EL-4) were evaluated. EL-4 proliferation was resistant in vitro to IL
      18 and IFN-gamma. When 4 x 10(6) EL-4 cells were transplanted intravenously, the
      antitumor effects of IL-18 were not pronounced, and only a slight prolongation of
      the mean survival times was observed. The antitumor effects of IFN-gamma were
      even less apparent than those of IL-18. However, when mice were transplanted
      intravenously with 5 x 10(5) EL-4 cells, the extent of experimental visceral
      dissemination of EL-4 was markedly reduced in mice treated subcutaneously with IL
      18, resulting in an increase in survival time with some mice even cured. Although
      IL-18 was highly effective at inhibiting the development of EL-4 lymphoma
      dissemination in C57BL/6 mice, it could not inhibit the development of
      dissemination in mutant C57BL/6 beige (bg/bg) mice lacking NK cell activity. The
      efficacy of IL-18 was also significantly reduced in nude mice lacking T cells.
      These results suggest that antitumor efficacy of IL-18 is mediated primarily by
      NK cells, but that T cells are also required for the complete antitumor efficacy
      of IL-18.

PMID- 12048349
TI  - Construction and analysis of new vector systems with improved interleukin-18
      secretion in a xenogeneic human tumor model.
AB  - Interleukin (IL)-18 plays an important role in enhancing cellular immunity
      against cancer and bacteria. We constructed retroviral and adenoviral vectors
      that show improved secretion of bioactive murine IL-18 that could further enhance
      antitumor immunity in a murine model. Secretion of bioactive IL-18 was
      facilitated by fusing the leader sequences of prepro-parathyroid hormone (PTH) or
      IL-1 receptor antagonist (IL-1ra) to the 5; end of the mature murine IL-18 cDNA.
      Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid
      showed about 100-fold more IL-18 production and interferon (IFN)-gamma induction
      from splenocytes when compared with those carrying PTH/IL-18 hybrid. Repeated
      intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid
      ligated to IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human
      colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.IL
      18 was associated with significantly elevated levels of serum IL-18 and IFN-
      gamma. IL-18 administration also enhanced the cytostatic activity of peritoneal
      exudate cells against cancer cells. These improved viral vectors, which
      efficiently produce bioactive IL-18, could be used as a useful tool for cancer
      gene therapy.

PMID- 12048350
TI  - Cytokine-induced injury of the lacrimal and salivary glands.
AB  - Damages to the lacrimal and salivary glands that accompany various autoimmune
      diseases are categorized as secondary Sjogren syndrome. Cytokines and free
      radicals are thought to be responsible for the pathologic changes, but the
      precise mechanisms are not clear. We evaluated whether cytokines alone can cause
      the damages in these exocrine tissues, and whether gaseous molecules such as
      nitric oxide (NO) play a role in these injuries. Various knockout (KO) mice as
      well as wild-type mice were injected intraperitoneally (i.p.) with the
      proinflammatory cytokines, IL-12 and IL-18, singly or in combination. Concurrent
      administration of IL-12 and IL-18 to mice caused serious atrophy in the lacrimal
      and salivary glands, which was spared when each cytokine was singly administered.
      Microscopically, there were apparently no infiltrating cells; nonetheless,
      numerous apoptotic cells were observed in the epithelium, which was confirmed by
      DNA ladder formation on gel electrophoresis. Serum levels of IFN-gamma and
      NO2/NO3 were markedly elevated. Combined injections of IL-12 and IL-18 caused the
      same changes in Fas-deficient and Fas-ligand deficient mice, as well as in
      perforin-KO mice, but the same changes were not detected in inducible NO synthase
      KO mice or IFN-gamma KO mice. Thus, the synergistic effect of IL-12 and IL-18 was
      dependent on production of IFN-gamma and NO, but independent of Fas/Fas ligand
      system and perforin-dependent cytotoxic T cells. IL-18 together with IL-12 caused
      destructive changes in the glandular tissues without apparent lymphocyte
      infiltration. It is suggested that these cytokines can mediate apoptosis in
      glandular epithelial cells and that the elevated NO production is responsible for
      the change.

PMID- 12048351
TI  - Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells
      possibly through suppression of osteoclastic bone-resorption in nude mice.
AB  - Interleukin (IL)-18 exhibits antitumor as well as antiosteoclastogenic
      activities. These findings suggest that IL-18 is a potential tool for the
      treatment of cancers with associated osteolytic bone metastasis. We have
      previously shown that systemic daily administration of recombinant (r) IL-18
      inhibits the development of osteolytic bone metastasis by human breast cancer
      cells. Here we demonstrate that systemic daily administration of rIL-18 (1
      microg/mouse/d) for 21 days significantly inhibited the number and the total area
      of osteolytic bone metastasis by RWGT2 human lung cancer cells in nude mice. No
      severe adverse effects were observed. Natural killer (NK) cells did not increase
      in splenocytes from rIL-18-treated mice, and the in vitro NK activity of
      splenocytes against RWGT2 cells was only weakly enhanced in the presence of IL
      18. The administration of rIL-18 made no difference in the growth of subcutaneous
      tumors, histologic indices (mitotic index, apoptotic index, and Ki-67-labeling
      index) of subcutaneous tumors or metastatic bone foci, or in the number of
      osteoclasts along the bone surface adjacent to tumors. Moreover, serum levels of
      cytokines including interferon-gamma, IL-1alpha, IL-6, tumor necrosis factor
      alpha, and granulocyte/macrophage colony-stimulating factor, which regulate bone
      resorbing activity of osteoclasts, were evaluated. Among them, IL-6 was
      remarkably downregulated in rIL-18-treated mice. These findings suggest that IL
      18 inhibits osteolytic bone metastasis possibly through suppression of
      osteoclastic bone-resorption mediated in part by IL-6.

PMID- 12048352
TI  - Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a
      potential therapeutic target of cartilage degradation.
AB  - Osteoarthritis (OA) is characterized by articular cartilage degradation and
      hypertrophic joint changes. Interleukin (IL)-18 is a potent inducer of
      prostaglandin (PG) E2 in vitro. We determined the relation between IL-18 and PGE2
      in synovial fluid (SF) of human OA, and discussed the role of IL-18 in the
      pathogenesis of OA and also its therapeutic consequences. SF was collected from
      30 patients with knee OA. The concentrations of IL-18 and other cytokines
      including IL-1beta, tumor necrosis factor (TNF)-alpha, IL-6, and IL-8 were
      measured by enzyme-linked immunosorbent assay (ELISA). The concentration of PGE2
      was also assessed by inhibitory ELISA. The average value of IL-18 was 248 +/- 310
      pg/mL. The average value of PGE2 was 93 +/- 103 pg/mL. There was a relatively
      strong correlation between IL-18 and PGE2 (r = 0.78, p = 0.0001). In contrast, IL
      1beta was undetectable (cutoff point of 20 pg/mL), except for one case. TNF-alpha
      was also undetectable (cutoff point of 20 pg/mL), except for two cases. The
      average value of IL-6 was 1,310 +/- 2,623 pg/mL (n = 17), whereas IL-8 was 5,208
      +/- 6,031 pg/mL (n = 5). Furthermore, IL-6 and IL-8 correlated with IL-18 (r =
      0.69, p = 0.0024 and r = 0.87, p = 0.0527, respectively). Our results suggest
      that IL-18 could play a major role in vivo in inducing the production of PGE2,
      which in turn can cause cartilage degradation in OA pathogenesis. Thus, targeting
      this cytokine appears to be an important therapeutic approach in OA.

PMID- 12048353
TI  - Serum interleukin-18 concentrations in patients with inflammatory bowel disease.
AB  - Elevated expression of interleukin (IL)-18 mRNA and protein in intestinal mucosa,
      attributable to activated monocytes and macrophages in that site, has been
      reported in patients with inflammatory bowel disease (IBD). However, changes in
      serum IL-18 concentrations in patients with IBD have not been reported. We
      measured bioactive IL-18 in serum from patients with IBD, using an enzyme-linked
      immunosorbent assay (ELISA). Mean serum IL-18 concentrations in 5 patients with
      Crohn disease (CD) were 400 pg/mL, approximately 1.7 times higher than
      concentrations in 21 control subjects (p < 0.01). However, serum IL-18 was not
      increased in patients with ulcerative colitis (UC). These results suggest that
      like other T-helper type 1 (Th1) cytokines IL-18 may play a key pathogenetic role
      in Th1-mediated disorders, such as CD. Regulation and expression of IL-18 appears
      to differ between CD and UC, and serum IL-18 may be a useful clinical marker for
      CD.

PMID- 12048354
TI  - Plasma interleukin-18 levels in patients with psychiatric disorders.
AB  - There are an increasing number of reports on an association between the
      alteration of circulating cytokine levels and pathophysiology of psychiatric
      disorders. Plasma concentrations of interleukin (IL)-18 were measured in 13
      nonmedicated patients with psychiatric disorders. There was a significant
      elevation of IL-18 levels in patients with major depression (n = 8) and panic
      disorder (n = 5), compared with normal controls. The mean IL-18 value of our
      psychiatric patients was comparable with that of various somatic disorders
      reported. We suggest that the elevation of plasma IL-18 levels reflects the
      increased production and release of IL-18 in the central nervous system under
      stressful settings. We propose that the measurement of IL-18 plasma levels may
      provide a useful index for the involvement of immune system in psychiatric
      disorders.

PMID- 12048355
TI  - Hepatic injury induced by interleukin-18 administration: importance of preceding
      priming effect.
AB  - The priming effects of obstructive jaundice by bile duct ligation on interleukin
      (IL)-18-induced hepatic injury are investigated. The production of IL-12 and
      tumor necrosis factor-alpha increased 3 days after bile duct ligation. Subsequent
      IL-18 injection to rats with obstructive jaundice caused by BDL resulted in
      prominent interferon-gamma production and hepatic injury. These results suggest
      that IL-18 with IL-12 and/or tumor necrosis factor-alpha have synergistic effects
      on the induction of hepatic injury via interferon-gamma production on this model.

PMID- 12048356
TI  - Increased concentrations of plasma interleukin-18 in patients with hepatic
      failure 1 week after surgery.
AB  - We investigated the dynamic aspects of circulatory interleukin (IL)-18 in
      patients who underwent a hepatectomy. In patients with hepatic failure after
      surgery, plasma concentrations of IL-6 and IL-10 increased in the early phase;
      however, the plasma concentrations of IL-18 increased in the later phase after 1
      week. Interestingly, the increase in the plasma IL-18 concentration was
      correlated with that in serum bilirubin levels in hepatectomized patients. Hence,
      the decrease in the hepatic metabolism of IL-18 may cause the plasma accumulation
      of IL-18. This mechanism was confirmed using rat experiments. Intravenously
      administrated human IL-18 was excreted in bile. Furthermore, the plasma clearance
      of human IL-18 was prolonged in bile-duct-ligated rats. These results suggest
      that IL-18 is metabolized in the liver and excreted in bile, and an increase in
      plasma IL-18 in patients with hepatic failure reflects the decreased metabolism
      in the liver.

PMID- 12048357
TI  - gp120-Independent infection of CD4(-) epithelial cells and CD4(+) T-cells by HIV
      1.
AB  - Infection of CD4- cells by HIV-1 is well documented, but the mechanism
      responsible remains a matter of discussion. Previously we modified an HIV-1 virus
      strain, NL4-3, by deleting the Env proteins (gp41 and gp120) and inserting the
      enhanced green fluorescent protein (EGFP), and found that the Env(-) virus
      infects several types of CD4- cells. Here, we have prepared Env(-) virus from
      both the CD4- cell line, 293T, and the CD4+ cell lines, CEM and SUPT1, and found
      that HIV-1 Env(-) virus from either cell type is infectious for both CD4+ and
      several CD4- cell lines. Replication of HIV-1 Env(-) virus-infected cells was
      demonstrated by p24 gag protein assays and real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) of the culture medium from infected cells.
      Virus collected from the HIV-1-Env(-) infected cultures proved infectious to
      several CD4- cell lines. Our results suggest that HIV-1 infects both CD4- and
      CD4+ cells using a gp120-independent mechanism. This infection mechanism may
      provide new explanations for HIV-1 latency and persistent infection in patients.

PMID- 12048358
TI  - Inhibition of morphine-potentiated HIV-1 replication in peripheral blood
      mononuclear cells with the nuclease-resistant 2-5A agonist analog, 2-5A(N6B).
AB  - Opioids potentiate HIV-1 infection in vitro at least partly by suppressing
      immunoresponsive processes in human lymphocytes and monocytes. For example, it
      appears that morphine inhibits the interferon (IFN)-alpha, -beta, and -gamma
      mediated natural antiviral defense pathways in human peripheral blood mononuclear
      cells (PBMC). In this study, we show that restoration of a key component of the
      antiviral pathway reverses morphine-potentiated HIV-1 infection of human PBMC.
      The data show that HIV-1 replication is potentiated and RNase L activity is
      inhibited after morphine administration. Because HIV-1 inhibits the antiviral
      pathway at the level of 2',5'-oligoadenylate (2-5A) synthetase and p68 kinase,
      antiviral enzymes that require double-stranded RNA, we overcame this blockade by
      the addition of the nuclease-resistant, nontoxic 2-5A agonist, 2-5A(N6B), to PBMC
      in culture. Addition of 2-5A(N6B), but not zidovudine or saquinavir, to morphine
      treated PBMC completely reversed the morphine-induced potentiation of HIV-1
      infection. Further, 2-5A(N6B) significantly enhanced expression of both IFN-alpha
      and IFN-gamma. Also, increased expression of IFN-gamma was associated with a
      significant increase in expression of RANTES and monocyte chemotactic protein
      (MCP)-1, chemokines that may inhibit HIV-1 infection by blocking viral attachment
      to CCR2 and CCR5 co-receptors. Our results suggest that reactivation of the
      antiviral pathway by 2-5A agonists may be useful to inhibit opioid-potentiated
      HIV-1 replication.

PMID- 12048359
TI  - Hospital and outpatient health services utilization among HIV-infected patients
      in care in 1999.
AB  - BACKGROUND: The evolving epidemiology and therapeutic management of HIV disease
      has important implications for health care resource utilization in HIV-infected
      patients, and health care resource use data are also needed to support policy and
      financial decision making. METHODS: Demographic, clinical, and resource
      utilization data were collected from 9 U.S. HIV primary and specialty care sites
      in calendar year 1999. Rates of resource use were calculated for hospital
      admission, length of hospital stay, and outpatient clinic/office visits. RESULTS:
      The sample included 5255 patients from HIV primary care sites in 3 eastern, 3
      midwestern, and 3 western areas of the United States. Hospital admissions
      accounted for an annual mean of 297 days per 100 persons/y in 1999. Hospital days
      ranged from a low of 165 per 100 persons/mo for a CD4 > 500 cells/mm(3) to 840
      per 100 persons/mo for a CD4 < 50 cells/mm(3) (p <.01). Mean annual outpatient
      clinic/office visits were 10.7 per person in 1999. A declining CD4 level and an
      increasing HIV-1 RNA level were both associated with higher hospital and
      outpatient utilization. HAART use was associated with fewer hospital days, and a
      higher outpatient visit rate. Injecting drug use risk was associated with an
      increase in hospital days. African American race was associated with a higher
      number of hospital days, but a lower outpatient visit rate. Female gender was
      associated with higher outpatient utilization. Mean monthly inpatient and
      outpatient expenditures in 1999 were $423 and $168, respectively. CONCLUSION: As
      HIV care continues to evolve, data from our network of HIV providers will be
      useful in quantifying changes in HIV health services utilization to guide policy
      makers, as well as HIV care payers and providers.

PMID- 12048360
TI  - Male sexual dysfunction associated with antiretroviral therapy.
AB  - To determine whether treatment with protease inhibitors (PIs) is associated with
      male sexual dysfunction, we conducted a retrospective, cohort study of 254 adult
      male PI recipients who received care from the staff-model division of a large
      managed care organization in New England between 1993 and 1998. After a median of
      5.0 years of observation, 80 incident cases of sexual dysfunction were observed.
      Relative to unexposed individuals, the rate of sexual dysfunction adjusted for
      confounding was most elevated with use of ritonavir (hazard ratio [HR], 2.83; 95%
      confidence interval [CI], 1.34-5.97; p =.006) followed by indinavir (HR, 1.69;
      95% CI, 0.84-3.37; p =.14), nelfinavir (HR, 1.53; 95% CI, 0.66-3.54; p =.32) and
      saquinavir (HR, 1.25; 95% CI, 0.53-2.96; p =.60). We conclude that PIs,
      especially ritonavir, appear to increase the risk of sexual dysfunction.

PMID- 12048361
TI  - Impact of suppression of viral replication by highly active antiretroviral
      therapy on immune function and phenotype in chronic HIV-1 infection.
AB  - We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type
      hypersensitivity (DTH) responses in 28 male antiretroviral treatment-naive and
      experienced HIV-1-infected patients, matched pair-wise according to age and CD4+
      T-lymphocyte count. Median CD4+ T-lymphocyte counts were 441 cells/microL and 483
      cells/microL and median CD4+ T-lymphocyte nadirs were 435 cells/microL and 150
      cells/microL in both groups, respectively. Absolute numbers of circulating T
      lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were
      comparable in the two groups. Untreated patients had greater proportions of
      activated CD4+ (p <.05) and CD8+ (p <.01) T-cells expressing human leukocyte
      antigen (HLA)DR and CD38 and fewer CD8+ cells expressing CD28 (p <.05). DTH and
      LP responses were comparable in both groups except for HIVp24, LP responses, and
      mumps DTH responses, which were of greater magnitude in the group treated with
      highly active antiretroviral therapy (HAART) (p <.05). Thus, HIV-1-infected
      patients who experienced substantial increases in CD4+ T-lymphocyte counts after
      suppression of viral replication on HAART had fewer activated lymphocytes and
      similar immune function when compared with findings in untreated patients with
      similar CD4+ T-cell counts. HIV replication has minimal real-time effect on CD4+
      T-cell function in response to non-HIV antigens but helper T-cell responses to
      HIV-gag antigen are impaired during ongoing viral replication and may be restored
      by antiretroviral therapy.

PMID- 12048362
TI  - Dynamics of naive and memory CD4+ T lymphocytes in HIV-1 disease progression.
AB  - Understanding the dynamics of naive and memory CD4+ T cells in the immune
      response to HIV-1 infection can help elucidate typical disease progression
      patterns observed in HIV-1 patients. Although infection markers such as CD4+ T
      cell count and viral load are monitored in patient blood, the lymphatic tissues
      (LT) have been shown to be an important viral reservoir. Here, we introduce the
      first comprehensive theoretical model of disease progression based on T-cell
      subsets and virus circulating between the two compartments of LT and blood. We
      use this model to predict several trademarks observed in adult HIV-1 disease
      progression such as the establishment of a setpoint in the asymptomatic stage.
      Our model predicts that both host and viral elements play a role in determining
      different disease progression patterns. Viral factors include viral infectivity
      and production rates, whereas host factors include elements of specific immunity.
      We also predict the effect of highly active antiretroviral therapy and treatment
      cessation on cellular and viral dynamics in both blood and LT.

PMID- 12048363
TI  - On the use of magnitude of reduction in HIV-1 RNA in clinical trials: statistical
      analysis and potential biases.
AB  - Clinical trials endpoints based on magnitude of reduction in HIV-1 RNA levels
      provide an important complement to endpoints based on either virologic failure or
      a proportion of patients having HIV-1 RNA levels below a threshold value.
      However, reductions in HIV-1 RNA often are not completely observed, because many
      patients have HIV-1 RNA levels below the limit of quantification at the primary
      follow-up visit. The crude method of analyzing such data is to define all HIV-1
      RNA levels that fall below the limit of quantification as being equal to that
      limit of quantification. This method is widely used even though the
      underestimation inherent in such a method may also lead to underestimation of
      treatment difference in terms of HIV-1 RNA reduction. Analyses based on Kaplan
      Meier method and censored regression can be used to estimate such a reduction.
      When a high percentage of patients have HIV-1 RNA levels below the limit of
      quantification at the time of primary follow-up, which corresponds to censored
      observations, the Kaplan-Meier method does not always provide an estimate of the
      median HIV-1 RNA reduction. We discuss a statistical method to provide lower and
      upper limits of such median reduction or of other percentiles of reduction. We
      found that when the percentage of censoring is high, the censored method may
      overestimate the HIV-1 RNA reduction and then may also overestimate the treatment
      difference. Although the censored method is preferable to the crude method, when
      the level of censoring is high, we suggest computation of the upper and lower
      limits either to provide a range of potential values of HIV-1 RNA reduction or to
      detect overestimation by the censored method.

PMID- 12048364
TI  - Role of hepatitis C virus genotype in the development of severe transaminase
      elevation after the introduction of antiretroviral therapy.
AB  - OBJECTIVE: To assess the role of different hepatitis C virus (HCV) genotypes in
      the development of transaminase elevation after treatment with highly active
      antiretroviral therapy (HAART). DESIGN: Retrospective cohort study at one
      referral HIV outpatient clinic. METHODS: HCV genotype was determined in plasma
      samples from all consecutive HCV-HIV coinfected patients initiating HAART between
      March 1998 and January 2000. Clinical and laboratory data were recorded during
      the following 9 months. Severe transaminase elevation was defined as > or =
      fivefold increase over upper normal limits (AIDS Clinical Trials Group grades 3
      or 4) when baseline alanine transaminase (ALT) and aspartate transaminase (AST)
      values were normal, and as > or = 3.5-fold increase above baseline ALT and AST
      values if they were abnormal. RESULTS: Twelve of 70 subjects (17%) developed
      severe transaminase elevation. Their HCV genotypes were distributed as follows:
      type 1, 5/39 (13%); type 2, 0/3 (0%); type 3, 7/21 (33%); and type 4, 0/7 (0%).
      The incidence of severe transaminase elevation was significantly higher among
      subjects with HCV genotype 3 (HCV-3) compared with those with non-type 3 (OR, 4.4
      [95%CI, 1.2-16.1]; P =.02). In the multivariate analysis, HCV-3 remained
      associated with severe transaminase elevation when adjusted for baseline HCV
      viral load and degree of immune recovery seen during follow-up evaluation.
      CONCLUSIONS: HCV-3 is an independent risk factor for developing severe
      transaminase elevation after HAART. HCV genotyping before initiating
      antiretroviral therapy may be useful for assessing the risk of hepatotoxicity and
      for choosing the most appropriate drugs to prescribe for HIV-HCV coinfected
      patients. Given that the best response to interferon plus ribavirin occurs in
      patients with HCV-3, treatment should be specially encouraged in coinfected
      persons carrying HCV-3.

PMID- 12048365
TI  - Reduced HIV risk-taking and low HIV incidence after enrollment and risk-reduction
      counseling in a sexually transmitted disease prevention trial in Nairobi, Kenya.
AB  - There is an urgent need in sub-Saharan Africa to develop more effective methods
      of HIV prevention, including improved strategies of sexually transmitted
      infection (STI) prevention or an HIV vaccine. The efficacy of these strategies
      may be tested through clinical trials within cohorts at high risk for STI and
      HIV, such as female commercial sex workers. For ethical reasons, standard HIV
      prevention services, including access to free condoms, risk-reduction counseling,
      and STI therapy, will generally be offered to all study subjects. Because study
      subjects would often not otherwise have access to these prevention services, it
      is possible that enrollment in such clinical trials will itself reduce incidence
      rates of STI and HIV below expected levels, reducing the power to test the
      efficacy of the randomized intervention. We show that the provision of standard
      HIV prevention services as part of a randomized STI/HIV prevention trial is
      temporally associated with a dramatic reduction in sexual risk-taking, and that
      this reduction is directly associated with reduced STI incidence. This finding
      should be considered in the design of clinical trials with an endpoint of HIV
      incidence, in particular HIV preventive vaccine trials.

PMID- 12048366
TI  - Incidence of HIV infection in stable sexual partnerships: a retrospective cohort
      study of 1802 couples in Mwanza Region, Tanzania.
AB  - OBJECTIVE: To describe the dynamics of HIV transmission in stable sexual
      partnerships in rural Tanzania. DESIGN: Retrospective cohort study nested within
      community-randomized trial to investigate the impact of a sexually transmitted
      disease treatment program. METHODS: A cohort of 1802 couples was followed up for
      2 years, with the HIV status of each couple assessed at baseline and follow-up.
      RESULTS: At baseline, 96.7% of couples were concordant-negative, 0.9% were
      concordant-positive, 1.2% were discordant with the male partner being HIV
      positive, and 1.2% were discordant with the female partner being HIV-positive.
      Individuals living with an HIV-positive partner were more likely to be HIV
      positive at baseline (women: odds ratio [OR] = 75.7, 95% confidence interval
      [CI]: 33.4-172; men: OR = 62.4, CI: 28.5-137). Seroincidence rates in discordant
      couples were 10 per 100 person-years (py) and 5 per 100 py for women and men,
      respectively (rate ratio [RR] = 2.0, CI: 0.28-22.1). In concordant-negative
      couples, seroincidence rates were 0.17 per 100 py in women and 0.45 per 100 py in
      men (RR = 0.38, CI: 0.12-1.04). Individuals living in discordant couples were at
      a greatly increased risk of infection compared with individuals in concordant
      negative couples (RR = 57.9, CI: 12.0-244 for women; RR = 11.0, CI: 1.2-47.5 for
      men). CONCLUSION: Men were more likely than women to introduce HIV infection in
      concordant-negative partnerships. In discordant couples, incidence in HIV
      negative women was twice as high as in men. HIV-negative individuals in
      discordant partnerships are at high risk of infection, and preventive
      interventions targeted at such individuals are urgently needed.

PMID- 12048367
TI  - Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of
      infection.
AB  - To estimate the change in AIDS incubation time during three periods characterized
      by different availability of antiretroviral treatments, data from the French
      Hospital Database on HIV of 4702 HIV-1-positive subjects with a documented date
      of infection were analyzed. Times from seroconversion to AIDS were compared in
      three periods: period 1 from January 1992 to June 1995 (monotherapy); period 2
      from July 1995 to June 1996 (dual therapy); and period 3 from July 1996 to June
      1999 (triple therapy). Nonparametric survival analyses were performed to account
      for staggered entries in the database and during each period. From periods 1 to
      3, antiretroviral treatments were initiated earlier after infection, more
      subjects were treated, and the nature of regimens changed (25.6% of subjects were
      treated with monotherapy in period 1, 34.6% were treated with dual therapy in
      period 2, and 53.4% were treated with triple therapy in period 3). Compared with
      period 1, the relative hazard (RH) of AIDS was 0.31 in period 3 (95% confidence
      interval [CI]: 0.24-0.39). When comparing period 3 with period 2, the RH of AIDS
      was 0.36 (CI: 0.29-0.45). Assuming a log normal distribution, the median time to
      AIDS was estimated as 8.0 years in period 1 (CI: 6.0-10.6), 9.8 years in period 2
      (CI: 8.5, 11.2), and 20.0 years in period 3 (CI: 17.1-23.3). This lengthening in
      time to AIDS from 1992 to 1999 was particularly marked in the period after the
      introduction of triple therapy, including protease inhibitors.

PMID- 12048368
TI  - Association of HIV-1 viral phenotype in the MT-2 assay with perinatal HIV
      transmission.
AB  - A case-control design study was used to investigate the association of maternal
      HIV-1 phenotype in MT-2 cells at or near the time of delivery with perinatal
      transmission of HIV-1, controlling for maternal CD4 percentage and duration of
      rupture of membranes, in 48 transmitting and 96 non-transmitting HIV-1-infected
      mothers who gave birth between 1990 and 1995. The non-syncytium-inducing (NSI)
      phenotype was more commonly seen in transmitting mothers compared with non
      transmitting mothers (90% vs. 75%, p =.04). In a multivariable logistic
      regression model, the following maternal characteristics were significantly
      associated with HIV transmission: NSI phenotype (odds ratio [OR] = 6.08; 95%
      confidence interval [CI]: 1.73-21.35) and log(10) viral load (OR = 2.11; CI: 1.19
      3.74). Finally, the association of NSI phenotype with transmission was stronger
      in transmitting women who received azidothymidine during pregnancy compared with
      transmitters who did not.

PMID- 12048369
TI  - Risk networks and racial/ethnic differences in the prevalence of HIV infection
      among injection drug users.
AB  - Studies among injection drug users (IDUs) find a higher prevalence of HIV
      infection among black and Puerto Rican IDUs than among white IDUs. Risk behaviors
      seldom explain these differences. We examine how risk networks contribute to
      racial/ethnic variations in HIV prevalence. Six hundred sixty-two IDUs were
      recruited on the street in Bushwick (New York City), interviewed, and tested for
      HIV. Risk behaviors and networks were analyzed to explain racial/ethnic
      variations in HIV. Forty percent of IDUs were infected with HIV. HIV prevalence
      was greater for Puerto Ricans (45%) and blacks (44%) than for whites (32%).
      Egocentric sexual and drug risk networks were predominantly racially/ethnically
      homogeneous. After multivariate adjustments for risk behaviors and risk networks,
      black-white differences in HIV prevalence were no longer significant. Although
      differences between Puerto Ricans and whites persisted, post hoc analyses
      suggested that network partner characteristics might explain these differences.
      In Bushwick, racially/ethnically discordant risk partnerships involving black
      IDUs may function as potential bridges of transmission between groups.

PMID- 12048370
TI  - Impact of adherence and highly active antiretroviral therapy on survival in HIV
      infected patients.
AB  - OBJECTIVES: To assess the effect of antiretroviral therapy (ART) adherence on
      survival in HIV-infected patients. DESIGN: Cohort study at a single hospital in
      Barcelona, Spain. METHODS: Data on HIV-infected patients older than 18 years of
      age who began ART during the period 1990 to 1999 were analyzed. Patients were
      considered nonadherent if the total dose of antiretroviral drug was less than 90%
      of that prescribed. Adherence was assessed through self-report and hospital
      pharmacy appointments. Cox regression with time-dependent variables was used.
      RESULTS: A total of 1219 patients were included. The first ART was with
      monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy
      in 45.8%. In multivariate analysis, the variables that presented significant
      differences with respect to mortality were clinical stage at the beginning of
      treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14
      4.13), CD4 cell count (<200 cells/microL: RH = 5.89; CI: 3.44-10.10), type of
      treatment (monotherapy: RH = 9.76; CI: 4.56-20.90; bi-therapy: RH = 9.12; CI:
      4.23-19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77-8.46). CONCLUSIONS:
      The modifiable factors most strongly associated with survival were type of
      treatment and adherence. It would be desirable to accompany therapy with
      intervention strategies intended to improve adherence.

PMID- 12048371
TI  - Survival rates in NYC in the era of combination ART.
AB  - BACKGROUND: Since the advent of combined antiretroviral therapy in 1996,
      substantial decreases in HIV-related morbidity and mortality have been observed
      in the United States and other developed countries. To assess the effects on
      overall survival and for specific AIDS-defining illnesses (ADIs), survival among
      persons with AIDS (PWAs) in New York City (NYC) before and after the introduction
      of combination therapy was investigated. METHODS: Survival among 79,878 PWAs
      diagnosed between 1990 and 1998 and reported through March 2001 was estimated.
      Cumulative survival at 24 months among PWAs was estimated by actuarial methods,
      and Cox proportional hazards model adjusted for covariates was used to estimate
      the relative hazard (RH) of death for specific ADIs over time. RESULTS: Overall
      cumulative survival at 24 months increased from 43% among PWAs diagnosed during
      1990-1995 to 76% for those diagnosed 1996-1998. Improving survival for all ADIs
      was found among PWAs diagnosed after 1995, but changes for immunoblastic
      lymphoma, primary lymphoma of the brain, and invasive cervical cancer were only
      moderate and were statistically (p >.05) insignificant. Burkitt lymphoma,
      immunoblastic lymphoma, invasive cervical cancer, and primary lymphoma of the
      brain had the highest RH of death among PWAs diagnosed after 1995. CONCLUSIONS:
      Substantial improvements in survival after 1995 were found for all PWAs but
      varied by gender, race, risk, socioeconomic status, and specific ADIs. Consistent
      with other studies, neoplastic ADIs have shown less improvement than other
      diseases after 1995. The relatively poor outcome of PWAs with neoplastic diseases
      requires further investigation.

PMID- 12048372
TI  - Dropouts in a long-term follow-up study involving voluntary counseling and HIV
      testing: experience from a cohort of police officers in Dar Es Salaam, Tanzania.
AB  - BACKGROUND: Results of most population-based studies primarily are derived from
      people who responded positively and thereby continued to participate in such
      studies. It is, however, equally important to know the characteristics of study
      subjects who drop out to learn the reasons that kept them from continuing to
      participate in the study, especially because they had initially agreed to
      participate in such a study. In studies with long-term follow-up, reasons for
      nonresponse may provide invaluable information that may be gathered through
      continued contact with study subjects who have withdrawn from the study.
      OBJECTIVES: To determine characteristics of study participants who withdrew from
      an ongoing study of police officers, which involved counseling and HIV testing,
      and to determine reasons for their discontinued participation. METHODS:
      Demographic characteristics of a cohort of police officers who had been
      participating in a study to determine their suitability for HIV vaccine trials
      were analyzed. Characteristics of those who did not return for the second survey
      of appointments for HIV testing were compared with those who continued their
      participation. A randomly selected sample of 132 police officers who did not
      participate in the second survey of HIV testing were asked why they did not
      return. Answers were obtained from 84 people who had discontinued their
      participation. RESULTS: Of eligible police officers, 2087 (72.1%) responded to
      the call for follow-up appointments, whereas 807 (27.9%) did not return. Those
      who did not return to participate in the second survey had significantly higher
      rates of HIV seropositivity (17.2%) than those who did return (13.5%) (p <.05).
      The rate of return in unmarried participants was worse (p <.05) than the rate
      among married participants. Rates of sexual contacts with partners other than
      their spouses and levels of alcohol consumption did not differ between the two
      groups. Reasons for dropping out of the study included fear of knowing results of
      HIV testing in 54.6%, lack of time to continue in 34.5%, and fears about job
      security in 3.6%. CONCLUSION: Fears of finding out that one might be seropositive
      need to be answered at recruitment, and practical arrangements must be made to
      facilitate further follow-up. A bias for lower incidence might be introduced in
      vaccine trials if participants thought to be at highest risk for HIV infection
      discontinue participation.

PMID- 12048373
TI  - Reanalysis of the HIV-1 circulating recombinant form A/E (CRF01_AE): evidence of
      A/E/G recombination.
AB  - Circulating recombinant form (CRF) 01_AE caused an extensive HIV-1 epidemic in
      Thailand and Southeast Asia. Reanalysis of the recombination pattern of CRF01_AE
      suggested a more complicated pattern of mosaicism consisting of subtypes A, G,
      and E. These findings provide evidence that CRF01_AE originated from
      recombination between at least three different subtypes.

PMID- 12048374
TI  - Methodological approach used by Skowron et al.

PMID- 12048375
TI  - Bone mineral density abnormalities in patients with HIV infection.

PMID- 12048392
TI  - Acute complications of preeclampsia.

PMID- 12048394
TI  - Shoulder dystocia: an evidence-based evaluation of the obstetric nightmare.

PMID- 12048393
TI  - Postpartum hemorrhage: new management options.

PMID- 12048395
TI  - Pregnancy-related venous thromboembolism.

PMID- 12048396
TI  - Acute pulmonary complications during pregnancy.

PMID- 12048397
TI  - Maternal cardiac arrest in pregnancy.

PMID- 12048398
TI  - Obstetric infectious disease emergencies.

PMID- 12048399
TI  - The acute abdomen during pregnancy.

PMID- 12048400
TI  - Trauma in pregnancy.

PMID- 12048402
TI  - Urinary tract injury in pelvic surgery.

PMID- 12048403
TI  - Unexpected cancer diagnosed at gynecologic surgery.

PMID- 12048404
TI  - Preoperative management of the medically at-risk patient.

PMID- 12048405
TI  - Complications of laparoscopic surgery.

PMID- 12048406
TI  - Prevention and management of acute intraoperative bleeding.

PMID- 12048407
TI  - Intraoperative injury to the gastrointestinal tract and postoperative
      gastrointestinal emergencies.

PMID- 12048408
TI  - Abdominal incision wound breakdown.

PMID- 12048410
TI  - Fluid electrolyte and nutritional problems in the postoperative period.

PMID- 12048409
TI  - Cardiorespiratory emergencies associated with pelvic surgery.

PMID- 12048411
TI  - Thromboembolic complications in gynecologic surgery.

PMID- 12048412
TI  - Acute abdominal emergencies associated with pregnancy.

PMID- 12048413
TI  - Postoperative infection.

PMID- 12048414
TI  - A preliminary study of multidimensional pain inventory profile differences in
      predicting treatment outcome in a heterogeneous cohort of patients with chronic
      pain.
AB  - OBJECTIVE: The objective was to evaluate whether the Multidimensional Pain
      Inventory (MPI) is effective for predicting response to interdisciplinary
      treatment in a heterogeneous group of patients with chronic pain. Changes in
      patients' profiles to a predominantly adaptive coping status after treatment also
      were assessed. DESIGN: A prospective study was conducted of patients with an
      array of pain conditions. A standard evaluation battery, including measures of
      self-reported pain and disability, psychosocial functioning, helpfulness of the
      program, and medication use, was used for all patients before and after
      treatment. The MPI status of patients was evaluated and differential response to
      treatment was assessed. METHODS: Sixty-five consecutive patients with chronic
      pain were evaluated before and immediately after participation in an
      interdisciplinary pain treatment program. This heterogeneous pain-condition
      cohort was also differentiated on the basis of the MPI to evaluate potential
      differential response to treatment. RESULTS: Results revealed significant
      improvement among these patients with chronic pain when a comprehensive
      interdisciplinary pain-management program was administered. This improvement was
      seen across the variety of outcomes evaluated, including narcotic medication use.
      Most important, the MPI subgroup classification did not significantly predict the
      degree of positive treatment outcome; all subgroups improved. CONCLUSIONS:
      Although there were major differences in psychosocial functioning before
      treatment, the MPI was not found to significantly predict response to
      interdisciplinary treatment in a heterogeneous group of patients with chronic
      pain. Thus, a comprehensive interdisciplinary treatment program may achieve its
      full effectiveness across a wide array of pain/disability-related outcome
      variables, regardless of initial MPI profile categorization.

PMID- 12048415
TI  - Sex hormone suppression by intrathecal opioids: a prospective study.
AB  - OBJECTIVE: Sexual dysfunction and low testosterone levels have been observed
      previously in males with chronic noncancer pain treated with intrathecal opioids.
      To investigate the hypothesis that intrathecal opioids suppress the hypothalamic
      pituitary-gonadal axis, a prospective nonrandomized investigation of the function
      of this axis was undertaken. DESIGN: Ten males with chronic noncancer pain were
      evaluated for clinical and biochemical evidence of hypogonadism at baseline and
      during the first twelve weeks of intrathecal opioid therapy. RESULTS: Intrathecal
      opioid administration resulted in a significant (p <0.0001) reduction in serum
      testosterone, from 7.7 +/- 1.1 (mean +/- SEM) nmol/L at baseline to 2.0 +/- 0.7,
      2.8 +/- 0.5, and 4.0 +/- 0.9 nmol/L at 1, 4, and 12 weeks, respectively. This was
      associated with a reduction in libido and potency. Luteinizing hormone and
      follicle-stimulating hormone levels remained within reference ranges, indicating
      central rather than peripheral suppression. CONCLUSIONS: Administration of
      intrathecal opioids may result in hypogonadotrophic hypogonadism. As part of the
      consent for therapy process, patients should be informed about this effect and
      its management. With long-term intrathecal opioid administration, the
      hypothalamic-pituitary-gonadal axis should be monitored. Where indicated,
      testosterone replacement should be undertaken to improve sexual function and
      prevent the potential metabolic effects of hypogonadism, in particular,
      osteoporosis.

PMID- 12048416
TI  - Comparison of superficial and deep acupuncture in the treatment of lumbar
      myofascial pain: a double-blind randomized controlled study.
AB  - OBJECTIVE: The aim of the study was to compare the therapeutic effect of the
      superficial and in-depth insertion of acupuncture needles in the treatment of
      patients with chronic lumbar myofascial pain. DESIGN: A prospective randomized
      double-blind study of superficial and deep acupuncture was conducted. SETTING:
      The study was conducted in the Pain Service Unit of the University of Padova.
      PATIENTS: The study comprised 42 patients with lumbar myofascial pain who were
      divided into two equal groups (A and B). INTERVENTION: In group A, the needle was
      introduced in the skin at a depth of 2 mm, whereas in group B the needle was
      placed deeply into muscular tissue. The treatment was planned for a cycle of
      eight sessions. OUTCOME MEASURES: The intensity of pain was evaluated with the
      McGill Pain Questionnaire before and after treatment and at the 3-month follow-up
      examination. RESULTS: Although at the end of the treatment there was no evidence
      of significant statistical differences between the two different groups, pain
      reduction was greater in the group treated with deep acupuncture. A statistical
      difference existed between the two groups at the 3-month follow up, with a better
      result in the deeply stimulated group. CONCLUSIONS: Clinical results show that
      deep stimulation has a better analgesic effect when compared with superficial
      stimulation.

PMID- 12048417
TI  - Treatments for chronic pain associated with spinal cord injuries: many are tried,
      few are helpful.
AB  - OBJECTIVE: The objective was to investigate, in two community samples of people
      with spinal cord injuries, the frequency of use of different pain treatments and
      the perceived helpfulness of these treatments. DESIGN AND SETTING: A postal
      survey was conducted in the community. PARTICIPANTS: The participants were 471
      persons aged 18 years or older who had spinal cord injuries and pain. There were
      2 separate samples (n = 308 and n = 163). OUTCOME MEASURES: The pain treatments
      used, the helpfulness of these treatments, and the Chronic Pain Grade
      questionnaire answers were assessed. RESULTS: Respondents reported multiple pain
      treatments (range of 0-14 and median of 4 in sample 1; range of 0-16 and median
      of 4 in sample 2). The most commonly reported treatments were oral medications
      and physical therapy. Medication types most commonly reported were nonsteroidal
      anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. The treatments
      rated as most helpful were opioid medications, physical therapy, and diazepam
      therapy, and those rated as least helpful were spinal cord stimulation,
      counseling or psychotherapy, administration of acetaminophen, and administration
      of amitriptyline. Alternative treatments reported as most helpful were massage
      therapy and use of marijuana. Acupuncture was tried by many but was rated as only
      moderately helpful. CONCLUSIONS: This survey of two large samples of community
      dwelling individuals with spinal cord injury-related chronic pain indicates that
      multiple pain treatments are tried but only a few are rated as more than somewhat
      helpful. Furthermore, the treatments that are most commonly reported are not
      always those that are rated as most helpful. The findings point to a number of
      potentially fruitful directions for future research.

PMID- 12048418
TI  - Associations between pain, grip strength, and manual tests in the treatment
      evaluation of chronic tennis elbow.
AB  - OBJECTIVE: The objective was to assess the associations between changes in pain
      and grip strength and manual tests among patients with chronic tennis elbow.
      DESIGN: Measurements for 45 consecutive patients with unilateral tennis elbow
      were made before and after an exercise intervention. SETTING: The setting was a
      physiatric outpatient clinic. PATIENTS: The patients were 45 persons with chronic
      unilateral tennis elbow: 32 women and 13 men. The mean age was 44 (31-54) years;
      mean duration of symptoms was 35 (10-66) weeks. OUTCOME MEASURES: Manual tests,
      pressure pain thresholds at three cubital points, a pain questionnaire, a pain
      drawing, and grip strength measurements were assessed. RESULTS: Grip strength
      became normal during the treatment. Pressure pain thresholds reached 66% of that
      of the healthy arm. Lowered pain thresholds and changes in pain thresholds of the
      lateral epicondyle were strongly associated with the findings in the manual
      tests. Mills test and resisted wrist extension tests were associated with
      perceived pain, and resisted wrist extension tests also were associated with
      decreased grip strength. Pain on palpation was associated with lowered pain
      thresholds at the lateral epicondylus and with perceived pain under physical
      load. After the treatment, for 13 patients all 4 manual tests were still
      positive; for 17 patients, 3 were still positive; and for 5 patients, all were
      negative. Positive clinical tests were associated with lowered pain thresholds,
      decreased grip strength, and high perceived pain scores. CONCLUSIONS: Pain
      thresholds at the lateral epicondyles are strongly associated with pain on
      palpation and with a positive Mills test. Resisted wrist extension test results
      reflect decreased grip strength. Impaired function of the hand is associated with
      the number of positive clinical tests. Pain threshold evaluation is a simple,
      easy, inexpensive method that provides useful additional quantitative data on
      pain and disability among patients with chronic tennis elbow.

PMID- 12048419
TI  - Functional abnormalities of the cervical cord and lower medulla and their effect
      on pain: observations in chronic pain patients with incidental mild Chiari I
      malformation and moderate to severe cervical cord compression.
AB  - OBJECTIVE: Abnormalities of central sensory processing may play a role in the
      pathogenesis of chronic pain. The Chiari I malformation is a congenital hindbrain
      anomaly characterized by protrusion of the cerebellar tonsils into the upper
      cervical canal, with variable effects on the lower brain stem and cervical cord.
      The purpose of this study was to compare sensory function and pain among patients
      with chronic pain who had these disorders incidentally diagnosed, to assess the
      effect on pain in these patients in comparison with those without central nervous
      system disease. DESIGN: Retrospective study in which pain, mood, and sensory
      function in 32 patients with chronic pain who had mild Chiari I malformation were
      compared with that in 53 patients with chronic pain who had moderate to severe
      compression of the cervical spinal cord and 52 patients with chronic pain who had
      no apparent central nervous system disorder. Data had been collected previously
      as part of standard clinical assessments, including clinical neurological
      examinations, quantitative sensory testing, pain drawings, and psychometric
      testing with the Symptom Checklist 90. PATIENTS: All subjects were patients of a
      hospital-based pain management practice who had been accepted for treatment over
      a 5-year period. RESULTS: Both the Chiari I and cervical compression groups had
      long tract signs evident on clinical neurological examination. Quantitative
      sensory testing indicated elevations in the trigeminal territory among patients
      with Chiari I malformation and on the neck, hands, and feet in both the Chiari I
      and cervical compression groups. The extent of pain and mood disturbance was
      greatest in the Chiari I group and least in the group with no central nervous
      system disorder. Complex regional pain syndrome, fibromyalgia, and temporal
      mandibular joint disorder were more common among the Chiari I malformation group
      than among the other groups. CONCLUSIONS: Quantitative sensory analysis indicates
      sensory dysfunction associated with Chiari I malformation and cervical cord
      compression. The pattern of sensory abnormality is consistent with medullary
      dysfunction among the patients with Chiari I malformation and cervical cord
      dysfunction among cord compression patients. There were differences in the types
      and extent of pain and the associated disorders of mood observed among the
      cohorts defined above. These differences may be partly due to the presence and
      location of central sensory dysfunction.

PMID- 12048420
TI  - A comparison of modality-specific somatosensory changes during menstruation in
      dysmenorrheic and nondysmenorrheic women.
AB  - OBJECTIVE: The objective was to evaluate somatosensory thresholds to a
      multimodality stimulation regimen applied both within and outside areas of
      referred menstrual pain in dysmenorrheic women, over four phases of confirmed
      ovulatory cycles, and to compare them with thresholds in nondysmenorrheic women
      during menstruation. DESIGN: Twenty dysmenorrheic women with menstrual pain
      scoring 5.45 +/- 0.39 cm (mean +/- standard error of mean) on a visual analog
      scale (10 cm) participated. Fifteen nondysmenorrheic women with a menstrual pain
      score of 0.4 +/- 0.2 cm participated as controls. Ovulation was confirmed by an
      enzyme-multiplied immunoassay technique. Menstrual pain was described with the
      McGill Pain Questionnaire. Areas within menstrual pain referral were two
      abdominal sites and the midline of the low back, and the arm and thigh were the
      control areas. The pressure pain threshold (PPT) and pinch pain threshold were
      determined by a hand-held electronic pressure algometer, the heat pain threshold
      (HPT) by a contact thermode, and the tactile threshold with von Frey hairs.
      RESULTS: In dysmenorrheic women the McGill Pain Questionnaire showed a larger
      sensory and affective component of pain than the evaluative and miscellaneous
      groups. The HPT and PPT were lower in the menstrual phase than in the ovulatory,
      luteal, and premenstrual phases, both within and outside areas of referred
      menstrual pain (p <0.01), with a more pronounced decrease at the referral pain
      areas. The pinch pain threshold was lower in the menstrual phase than in the
      ovulatory phase (p <0.02), and the tactile threshold did not differ significantly
      across the menstrual phases or within any site. Dysmenorrheic women had a lower
      HPT at the control sites and a lower PPT at the abdomen, back, and control sites,
      than in those of nondysmenorrheic women in the menstrual phase. CONCLUSIONS: The
      results show reduced somatosensory pain thresholds during menstruation to heat
      and pressure stimulation, both within and outside areas of referred menstrual
      pain in dysmenorrheic women. Dysmenorrheic women showed a lower HPT at the
      control sites and a lower PPT at all the sites than those for nondysmenorrheic
      women in the menstrual phase. The altered somatosensory thresholds may be
      dependent on a spinal mechanism of central hyperexcitability, induced by
      recurrent moderate to severe menstrual pain.

PMID- 12048421
TI  - Disruption of thermal perception in a multiple sclerosis patient with central
      pain.
AB  - OBJECTIVE: To investigate integrative thermal perception in a patient with
      multiple sclerosis. DESIGN: Quantitative thermosensory testing was used to
      evaluate pain and other sensations produced by heat, cold, and the thermal grill
      pain illusion. PATIENT: The authors report on a 43-year-old patient with central
      pain manifest most strongly in her left arm and hand, contralateral to an upper
      cervical spinothalamic lesion due to multiple sclerosis. OUTCOME MEASURES AND
      RESULTS: Quantitative thermosensory testing showed that the patient had heat
      hypalgesia (no pain with stimuli of 45-50 degrees C) and cold allodynia (pain
      with innocuous cool temperatures, 25-10 degrees C). Whereas healthy subjects
      rated 20 degrees and 40 degrees C as nonpainful, but the thermal grill
      (intermixed 20 and 40 degrees C stimuli) as painful, the patient rated the
      thermal grill as less painful than 20 degrees C. CONCLUSIONS: The absence of
      thermal grill-evoked pain is consistent with the hypothesis that in some cases of
      central pain the loss of the thermosensory pathway results in disruption of the
      normal cold inhibition of burning pain.

PMID- 12048422
TI  - Long-term pain control in trigeminal neuralgia with local anesthetics using an
      indwelling catheter in the mandibular nerve.
AB  - OBJECTIVE: The authors sought to determine the usefulness of long-term continuous
      trigeminal nerve block with local anesthetics using an indwelling catheter in a
      patient with trigeminal neuralgia. DESIGN: The study design included pain control
      in a patient with trigeminal neuralgia until the time of neurosurgical operation.
      SETTING: The study was conducted in the Dental Hospital of Tokyo Medical and
      Dental University. PATIENT: The patient was a 78-year-old woman with trigeminal
      neuralgia in the right maxillary region. Her pain could not be controlled by
      carbamazepine and was unbearable. INTERVENTION: The authors estimated the
      patient's pain intensity, quality, and locality using a visual analog scale to
      determine the effectiveness of continuous nerve block. OUTCOME MEASURES: Visual
      analog scores were measured during treatment. The treatment term was divided into
      three periods according to the difference of the catheter location and injection
      protocol (premandibular nerve block, infuser injection, and patient-controlled
      analgesia [PCA] pump injection). The authors also examined the patient's general
      condition and blood concentration of drugs. RESULTS: The visual analog values
      were 44.8 +/- 3.6, 26.7 +/- 3.5, and 11.9 +/- 3.1 mm in each period,
      respectively. The value in the PCA pump infusion period was significantly lower
      than that in the other periods. No side effects of the local anesthetics were
      observed on the patient's systemic condition. CONCLUSIONS: The authors controlled
      trigeminal neuralgia pain by blocking the mandibular nerve with local anesthetics
      administered through an indwelling catheter. Because the continuous nerve block
      with local anesthetics is reversible and only mildly toxic, this method is
      beneficial for pain control in patients with trigeminal neuralgia scheduled to
      undergo microvascular decompression.

PMID- 12048423
TI  - A novel treatment of postherpetic neuralgia using peppermint oil.
AB  - BACKGROUND: Postherpetic neuralgia remains a difficult problem to treat. A number
      of therapies have been shown to be effective, but some patients have intractable
      pain. PATIENT: The case of a 76-year-old woman whose pain had been resistant to
      standard therapies is described. The pattern of quantitative sensory testing
      results for this patient led the authors to believe that she had an "irritable
      nociceptor" type of pathophysiology. INTERVENTION: The patient was instructed to
      apply neat peppermint oil (containing 10% menthol) to her skin, resulting in an
      almost immediate improvement in her pain. This pain relief persisted for 4-6
      hours after application of the oil. RESULTS: The patient was successfully treated
      with topical peppermint oil. During 2 months of follow-up she has had only a
      minor side effect, with continuing analgesia. The authors believe this is the
      first evidence of peppermint oil (or menthol) having a strong analgesic effect on
      neuropathic pain. The possible mechanisms of action of peppermint oil are
      discussed.

PMID- 12048425
TI  - Ambulatory monitoring of blood pressure in growth hormone-deficient adults.
AB  - The aim of this study was to evaluate the 24-h pattern of blood pressure in
      adults with growth hormone deficiency using ambulatory blood pressure monitoring.
      We therefore evaluated the mean systolic and diastolic blood pressures, systolic
      and diastolic blood pressure loads and diurnal blood pressure rhythm. We used an
      auscultatory-type monitor, the measurements being made at 10-15 min intervals
      during the day and 20-30 min intervals at night. We included patients with a
      growth hormone peak of less than 3 ng/ml in at least two stimulation tests: the
      insulin tolerance and glucagon tests. The exclusion criteria were mental
      illnesses, pregnancy, diabetes mellitus, blood pressure higher than 160/90 mmHg,
      the use of growth hormone in the previous 12 months, severe acute illnesses,
      chronic liver or kidney disease and a history of malignancy. The results were
      interpreted according to the II Brazilian Consensus for the utilization of
      ambulatory monitoring. The study population comprised 27 adult patients with
      growth hormone deficiency, 11 male and 16 female, with an age range of 21-62
      years. Five had developed the condition during childhood, whereas the remainder
      had adult-onset growth hormone deficiency. The mean systolic (115 +/- 16.7 mmHg)
      and diastolic blood pressure loads (75.51 +/- 1.90 mmHg) were normal. There was a
      tendency towards a lower blood pressure in patients with childhood-onset growth
      hormone deficiency when compared with their adult-onset counterparts. Men had a
      lower systolic blood pressure than women, the same pattern being found for mean
      diastolic blood pressure. Multiple regression analysis showed that age was the
      only independent variable with the statistical power to explain the variance of
      blood pressure in this group of patients. The incidence of non-dippers was
      37.03%. Growth hormone deficiency thus seems to be associated with a change in
      the 24-h blood pressure pattern, with a high incidence of non-dippers.

PMID- 12048424
TI  - Methadone for phantom limb pain.
AB  - OBJECTIVE: The objective of this case series was to determine if severe phantom
      limb pain could be reduced with oral methadone. DESIGN: Four cases of phantom
      limb pain refractory to multiple treatment modalities were treated with oral
      methadone. SETTING: Pain clinic at a major university medical center. PATIENTS:
      Four patients with severe, intractable phantom limb pain. INTERVENTION: Oral
      methadone was administered, starting with a low dose of 2 to 5 mg twice a day or
      three times a day and slowly titrated upward to achieve pain relief. OUTCOME
      MEASURES: Repeated administration of a visual analog scale for pain. RESULTS AND
      CONCLUSIONS: Administration of oral methadone may be of value in the treatment of
      phantom limb pain; controlled clinical trials would be appropriate to verify this
      observation.

PMID- 12048426
TI  - The effect of differences in measurement procedure on the comparability of blood
      pressure estimates in multi-centre studies.
AB  - The procedures for obtaining blood pressure measurements, and their quality of
      performance, should be similar between epidemiological studies to allow a valid
      comparison of blood pressure distribution and prevalence of hypertension between
      study populations. However, considerable methodological variation currently
      exists as there are several international guidelines on blood pressure
      measurement and a standard method of measurement has not yet been agreed. This
      paper reviews the literature in order quantitatively to define systematic
      differences between blood pressure measurements resulting from differences in arm
      used, body position, number of measurements, verbal communication, cuff size
      applied and measuring device used. The results were applied to differences in
      procedure between European Prospective Investigation into Cancer and Nutrition
      (EPIC) study centres, showing that blood pressure measurements may systematically
      differ between centres by as much as 10 mmHg for procedural reasons alone. For
      most reviewed methodological differences, it was possible to at least estimate a
      range of systematic error. There are, however, additional possible causes of
      systematic variation, for example arm position, postprandial hypotension and
      diurnal blood pressure variation, that could not be taken into account. It may be
      possible to make only a partial correction for the systematic inter-centre
      variation of the EPIC blood pressure measurements. This study highlights the
      importance of standardized protocols for blood pressure measurements in
      epidemiological studies.

PMID- 12048427
TI  - Diurnal blood pressure patterns in long-term care settings.
AB  - BACKGROUND: Some research suggests that individuals whose blood pressure does not
      decline at night may be at increased risk of end-organ damage. Few studies have
      examined ambulatory blood pressure among elders, particularly those living in
      institutions. This study therefore evaluates ambulatory blood pressure variation
      in two groups of institutionalized elderly, independent living and nursing home
      residents. It was suggested that the nursing home sample would have a higher rate
      of non-dipping than the independent-living residents. DESIGN AND METHODS: Twenty
      seven residents (aged 87 +/- 8 years) of a nursing home facility and 29 residents
      (aged 80 +/- 6 years) from two independent living facilities wore ambulatory
      monitors for approximately 24 h. Several definitions of dipping were examined.
      RESULTS: Neither mean daytime nor mean night-time systolic blood pressure
      differed between the two groups. Daytime diastolic blood pressure was
      significantly higher in the independent living sample, as was night-time
      diastolic pressure in the nursing home residents. Neither asleep nor awake blood
      pressure varied significantly between groups. The decline in night-time blood
      pressure and sleep blood pressure was significantly greater among the independent
      living residents (P < 0.05). Ratios of night-time/daytime and asleep/awake blood
      pressure were significantly higher in the nursing home group. Non-dippers were
      significantly more frequent among the nursing home residents. CONCLUSIONS:
      Nursing home residents were significantly more likely to be non-dippers. Both
      groups of resident were more frequently non-dippers than were individuals in
      community-dwelling samples. The high prevalence of non-dipping among
      institutionalized elderly people may be a result of age, health status or
      institutional activity patterns.

PMID- 12048428
TI  - Uncontrolled early morning blood pressure in medicated patients: the ACAMPA
      study. Analysis of the Control of Blood Pressure using Abulatory Blood Pressure
      Monitoring.
AB  - BACKGROUND: A blood pressure surge during the early morning may help to
      precipitate cardiovascular events. The objective of this study was thus to assess
      the blood pressure behaviour profile of early morning blood pressure in patients
      receiving antihypertensive treatment. DESIGN: The ACAMPA study is a multi-center,
      open, prospective, observational study that was carried out by 24 investigators
      in Spain. METHODS: Two hundred and ninety patients with essential hypertension
      who had been receiving the same antihypertensive treatment for at least 2 months
      were included in the study. Office blood pressure was measured before taking
      medication in the morning, and 24-h ambulatory blood pressure monitoring was
      performed. In addition to the automatic measurements, patients were instructed to
      take a blood pressure measurement after waking. RESULTS: The group analysis used
      240 patients (mean age 54 years, including 101 males). Good clinical control (a
      blood pressure of less than 140/90 mmHg) was found in 53 cases (22%). The
      differences between the clinical and ambulatory readings during the period of
      activity were minimal in the group with good control (127 +/- 9/81 +/- 7 versus
      127 +/- 10/81 +/- 7 mmHg; non-significant) but were significant in the group with
      poor control (155 +/- 16/93 +/- 10 versus 138 +/- 14/86 +/- 11 mmHg; P < 0.001).
      The blood pressure values were synchronized according to the moment of awakening.
      In almost half of the patients with good control, systolic and diastolic blood
      pressure values were higher than normal (135/85 mmHg); in those patients with
      poor control, this fraction rose to over 70%. The proportion of patients
      presenting high blood pressure values became even greater during the second hour
      after waking (62% in patients with good blood pressure control and 82% in those
      with poor control). CONCLUSIONS: In a large number of antihypertensive patients
      receiving treatment, blood pressure values remain high during the early-morning
      hours. At least half of those patients with an apparently well-controlled office
      blood pressure do not have their blood pressure under control for the period
      shortly after waking.

PMID- 12048429
TI  - Improved automatic analysis of ambulatory blood pressure data based on precise
      detection of individual night-time from diurnal profile of heart rate.
AB  - BACKGROUND: Software programs sold with ambulatory blood pressure monitoring
      (ABPM) devices are designed to use some set 'typical' night-time (e.g. 2300-0700)
      to estimate daytime/night-time blood pressure (BP) with limited accuracy.
      Alternative use of individual periods of sleep/wakefulness from patient diaries
      is time consuming and subjective. We developed a simple mathematical algorithm
      for the detection of the 'night-time' as a period of low values in diurnal
      profiles of heart rate (HR) allowing accurate automatic analysis of daytime/night
      time blood pressure. To test this technique we designed a software application
      allowing automatic analysis of ABPM data based on the different night-time
      definitions, including the developed algorithm and compared reproducibility of
      the degree of BP dipping produced by the different methods across two days of 48
      h ABPM. METHODS: A 48-h ABPM study was performed in 33 patients with
      uncomplicated stage II hypertension. Means and standard deviations (SD) of the
      differences in the degree of BP dipping between two 24-h periods of 48-h ABPM
      were obtained separately for three methods of night-time definition: automatic
      detection from individual HR profiles, fixed 2300-0700 h interval and sleep time
      from patient diaries. RESULTS: Reproducibility of the BP dip estimation across 2
      days of BP monitoring was significantly better for night-time detected from
      individual HR profiles than for the fixed 2300-0700 h interval or sleep time from
      diary. The SD of the differences was 6.7/8.2 compared with 13.5/18.3 and
      13.0/14.8 respectively (systolic BP/diastolic BP, mmHg). CONCLUSIONS:
      Implementation of the developed method of night-time definition may significantly
      improve automatic analysis of ABPM data.

PMID- 12048430
TI  - Determination of accuracy in neonates for non-invasive blood pressure device
      using an improved algorithm.
AB  - BACKGROUND: New software (SuperSTAT(R) algorithm) with enhancements aimed at
      shorter determination times was developed for a non-invasive blood pressure
      (NIBP) device and a clinical evaluation was conducted to verify accuracy.
      OBJECTIVE: To determine the accuracy of the new algorithm according to ANSI/AAMI
      SP10-1992 and SP10A-1996 American National Standard for Electronic or Automated
      Sphygmomanometers. METHODS: The blood pressure values obtained from the test
      device were compared to the intra-arterial blood pressure reference standard
      (IBP). RESULTS: The NIBP and IBP comparisons for systolic, diastolic, and mean
      arterial pressure met the 1992 ANSI/AAMI accuracy standards by being within a
      mean difference of +/- 5 mmHg and standard deviation of < or = 8 mmHg.
      CONCLUSION: Non-invasive blood pressure determinations taken with the new
      algorithm, developed to provide greater patient comfort due to faster
      determinations, were accurate when compared to neonatal IBP.

PMID- 12048431
TI  - Systematic error in the determination of nocturnal blood pressure dipping status
      by ambulatory blood pressure monitoring.
AB  - BACKGROUND: Vertical displacement of the arm relative to the heart causes inverse
      changes in blood pressure of approximately 0.8 mmHg for every centimetre change
      in arm position. Therefore a potential confounding issue in assessing diurnal
      variation in blood pressure during ambulatory blood pressure monitoring (ABPM) is
      arm position during sleep. An increase in the number of patients with 'excessive'
      nocturnal dipping (> 20% decrease in night/day blood pressure) was observed
      following the creation of an instructional videotape in which patients were
      advised to muffle the noise of the monitor with a pillow at night. This raised
      the possibility that patients were placing their arm on top of the pillow
      reducing nocturnal blood pressure readings. DESIGN: Ambulatory blood pressure
      monitoring data from 184 patients prior to and from 193 patients following
      specific instructions not to put their arm on top of the pillow was examined.
      RESULTS: Following the instructions, the percentage of patients with 'excessive'
      nocturnal dipping in blood pressure decreased (excessive systolic dipping 17.4
      versus 8.8%, P = 0.014; excessive diastolic dipping 37 versus 24.4%, P = 0.01).
      Consistent with an increase in the ratio of nocturnal/day pressures, there was an
      increase in the percentage of patients with inadequate nocturnal dipping (< 10%
      decrease in night/day blood pressure; systolic dipping 33.7 versus 45.6%, P =
      0.02; diastolic dipping 13.0 versus 31.6%, P < 0.001) CONCLUSION: Instructing
      patients to avoid resting their arm on a pillow at night has a substantial effect
      on the classification of nocturnal dipping status. Patients need clear
      instructions not to place their arm on a pillow at night during blood pressure
      monitoring.

PMID- 12048443
TI  - Palliative care in district general hospitals: the nurse's perspective.
AB  - Most patients with a terminal illness die in hospital, yet the opinions of their
      prime carers are largely ignored. This study investigated registered nurses'
      perceptions of palliative care in district general hospitals. A random sample of
      263 nurses was surveyed, using a pre-piloted questionnaire, and results showed
      that 70% of general ward nurses believe that managing care of the dying is an
      integral part of hospital care. However, their dissatisfaction with the care they
      give is reflected in the mere 8% who consider hospital an ideal setting for
      patients who are dying. Although nurses are confident in their physical/clinical
      role, dealing with psychosocial issues is more problematic. A minority feel
      confident in discussing death and dying with the patient. Barriers to optical
      palliative care on general wards were perceived as lack of appropriate education
      and training, work pressures, and lack of support from medical colleagues and
      managers.

PMID- 12048432
TI  - An ambulatory blood pressure monitoring study of the comparative antihypertensive
      efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan.
AB  - BACKGROUND: The primary objective of this study was to compare the change from
      baseline in mean diastolic ambulatory blood pressure (ABP) at 24 h post dose
      (trough measurement) after 8 weeks of treatment with irbesartan or valsartan in
      subjects with mild-to-moderate hypertension. Secondary objectives included
      comparing the mean changes from baseline in systolic ABP at trough; 24-h ABP;
      morning and night-time ABP; self-measured systolic blood pressure (SBP) and
      diastolic blood pressure (DBP); and office-measured SBP and DBP at trough.
      DESIGN: After a 3-week, single blind, placebo lead-in period, 426 subjects were
      randomized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks.
      METHODS: Ambulatory blood pressure measurements were obtained at baseline and at
      week 8. Self-measured morning and evening DBP and SBP readings were obtained at
      home over a 7-day period at baseline and at week 8. Office-measured seated DBP
      and SBP measurements were obtained at trough, at baseline, and at week 8.
      RESULTS: Irbesartan demonstrated significantly greater reductions than valsartan
      for mean change from baseline in diastolic ABP at trough (-6.73 versus -4.84
      mmHg, respectively; P = 0.035). Irbesartan produced significantly greater
      reductions than valsartan for mean systolic ABP at trough (-11.62 versus -7.5
      mmHg, respectively; P < 0.01) and for mean 24-h diastolic ABP (-6.38 versus -4.82
      mmHg, respectively; P = 0.023) and systolic ABP (-10.24 versus -7.76 mmHg; P <
      0.01). Irbesartan also produced significantly greater reductions than valsartan
      for office-measured seated DBP (-10.46 versus 7.28 mmHg, respectively; P < 0.01)
      and SBP (-16.23 versus -9.96 mmHg, respectively; P < 0.01) and for self-measured
      morning DBP (-6.28 versus -3.75 mmHg, respectively; P < 0.01) and SBP (-10.21
      versus -6.97 mmHg, respectively; P < 0.01). Both drugs were well tolerated.
      CONCLUSION: Irbesartan was more effective than valsartan in reducing DBP and SBP
      at trough and in providing greater overall 24-h blood pressure-lowering efficacy.

PMID- 12048444
TI  - The dilemmas of resource allocation.

PMID- 12048445
TI  - Hospice at home 1: the development of a crisis intervention service.
AB  - This article is the first in a series of two which report on the development and
      evaluation of a rapid response crisis intervention service for patients in the
      advanced stages of cancer. A number of recent studies have identified the need
      for rapid response teams who are able to provide palliative and specialist
      palliative care in the home setting (King et al, 2000; Mantz, 2000; Thomas,
      2001). By providing an overview of the relevant literature and describing the
      experience of developing this scheme the authors' aim is to share good practice
      with interested professionals who may be contemplating setting up similar
      schemes. This article outlines the development of a 'hospice at home' scheme
      until its launch and identifies the strategies used to ensure the early success
      of the project.

PMID- 12048446
TI  - Using philosophy, knowledge and theory to assess a patient with lymphoedema.
AB  - The way that the world around us is interpreted, the selective use of knowledge
      to inform patients and different theories to support nursing practice are
      concepts outlined in this article that have great importance in the holistic
      nature of the assessment of all patients. The development of lymphoedema is a
      unique experience for any patient and one that is interpreted by the patient
      according to previous experiences and knowledge. Patients bring to the assessment
      their own thoughts, beliefs and understanding of the world around them, together
      with knowledge acquired from many sources. In order to plan the most appropriate
      management for a patient's lymphoedema, the nurse is challenged to recognize
      his/her own thoughts and beliefs and the role they play in understanding the
      meaning that lymphodema has for each patient. Relevant knowledge, together with a
      theoretical background to practice can then be incorporated into a holistic
      framework for assessment of the patient with lymphodema.

PMID- 12048447
TI  - A patient-held record for cancer patients from diagnosis onwards.
AB  - This article presents the findings of a qualitative study looking at the content
      and use of a personally held record for cancer patients. The study was conducted
      in the York area of the UK over a 1-year period and the record was introduced to
      patients as near to diagnosis as possible. The record had three main sections:
      general information, communication sheets and a health diary. Users were invited
      to complete questionnaires and volunteer patients took part in independently
      facilitated focus group discussions. Patients liked the record and placed
      importance on access to information early in their treatment process. They valued
      the health diary as a means of therapy and personal reflection and shared
      information in the records with family and friends. The steering group
      coordinating the study believed there was sufficient positive feedback to warrant
      further work. However, the findings of regional and national working groups must
      be assessed before progressing to the next stage of development.

PMID- 12048448
TI  - Palliative sedation therapy: a review of definitions and usage.
AB  - Palliative care clinicians are faced with the challenge of managing a multitude
      of complex symptom combinations in patients for whom they care. Although many
      symptoms respond favourably to established protocols, others may remain
      refractory to such intervention. It is within the context of trying to manage
      such symptoms that the issue of palliative sedation therapy arises. The use of
      sedation in such circumstances is one that has prompted considerable debate in
      the palliative care literature. Discourse has been hampered, however, by a lack
      of consensus regarding the meaning and intent of palliative sedation therapy,
      when it should be used clinically and how it is to be achieved pharmacologically.
      There is a dearth of research examining the meanings ascribed to its use from the
      perspective of patients, families, and health-care providers. This article will
      provide an overview of these identified issues, and provide suggestions for ways
      in which palliative sedation therapy might further be examined and understood.

PMID- 12048449
TI  - Nurses' bedside manner: is it deteriorating?

PMID- 12048451
TI  - Introduction of a new nursing 'Code of Professional Conduct'.

PMID- 12048450
TI  - Should elderly patients with heart failure be in hospital?

PMID- 12048452
TI  - Overseas registered nurse who was found to be incompetent.

PMID- 12048453
TI  - Day surgery preoperative anxiety reduction and coping strategies.
AB  - Hospitalization, even in patients who are not faced with the prospect of surgery,
      is known to cause anxiety. One may, therefore, expect some degree of anxiety in
      patients attending for day surgery. Anxiety provokes a physiological stress
      response, which impedes the healing process. Thus, the reduction of preoperative
      anxiety is widely accepted as part of nursing care. This article investigates the
      coping strategies that patients adopt and the suitability of current anxiety
      reduction interventions. It argues that individual coping styles do not remain
      static but adapt according to need and proposes that, as a result of lack of
      awareness, the therapeutic potential of the nurse-patient relationship in anxiety
      reduction is being overshadowed by uncertainty-reduction approaches which place a
      disproportionate emphasis on the provision of information.

PMID- 12048454
TI  - Parents with colorectal cancer: 'What do I tell the children?'.
AB  - Whatever the age of the child, there is no easy way for a parent to explain
      serious, life-threatening illness. For children to hear that their parent is ill
      is devastating, especially if the parent has cancer and needs a permanent
      colostomy. The diagnosis of cancer can produce feelings of fear, confusion and
      uncertainty in patients and their close relatives. How difficult does this then
      become for the child battling to understand long medical words, alien hospital
      environments and an ill parent? The social taboos that surround body matter
      elimination are legion and therefore the surgical outcome of having a permanent
      stoma changes the individual's body image perception long-term. The two case
      studies presented in this article highlight this problem as well as the lack of
      suitable available literature.

PMID- 12048455
TI  - Setting up a multidisciplinary journal club in learning disability.
AB  - This article presents an account of how a journal club with a multidisciplinary
      membership from learning disability practice was set up. It presents a review of
      the literature which discusses the purpose, function and setting up of journal
      clubs. It outlines how topics were selected, the appraisal tool used to review
      articles and how findings from the reviews were disseminated to practice areas.
      The article in identifies the lack of research in the areas of learning
      disability practice. It demonstrates the positive aspects of working in
      collaboration with other members of the multidisciplinary team and how this
      provides opportunities for professional development. It identifies that support
      from management is essential in enabling staff to take time to attend and
      participate in the journal club.

PMID- 12048456
TI  - Health facilitation in learning disability: a new specialist role.
AB  - This article attempts to examine the important role of the health facilitator in
      learning disability and recommends that the specialist community learning
      disability nurse already has the appropriate skills and knowledge to carry out
      competently the role across the acute, primary and secondary care sectors. A
      model for community specialist learning disability practice already exists
      (Bollard and Jukes, 1999) but for health facilitation to have an impact a model
      of leadership and charge is recommended to be aligned to a model for practice. A
      CALECT model (a mnemonic which represents essential core roles and skills of a
      health facilitator) is proposed as a complementary vehicle to make facilitation
      work.

PMID- 12048457
TI  - Workplace stress and bullying: liabilities of the employer.

PMID- 12048458
TI  - Benefits of a course in behavioural analysis for health visitors.
AB  - Twenty-four health visitors participated in a 12-week course in behavioural
      intervention methods for work with children with behavioural difficulties. Each
      health visitor identified a family with child behavioural problems and worked
      with this family while attending the weekly training sessions. The course was run
      in 1998/99 and in 2000/01 for 12 health visitors. The 1998/99 trainees
      established a control group by identifying a second family experiencing similar
      difficulties. These families received the standard service for the same duration
      as the course. After the course, all health visitors demonstrated a significant
      increase in knowledge of behavioural techniques. Significant improvements were
      seen in measures of child behaviour and maternal mental health for both groups of
      intervention families, compared with non-significant improvements in the control
      families. The course's success in giving health visitors the skills and practice
      to develop effective behavioural strategies in work with child behavioural
      problems is also discussed.

PMID- 12048459
TI  - Vicair Academy Mattress in the prevention of pressure damage.
AB  - There are many costs associated with the development of pressure ulcers, both in
      terms of the patient experience and those associated with healing. If patients
      who are deemed to be at risk are identified and suitable preventive equipment is
      provided, incidence of pressure ulcer development can be reduced significantly.
      Pressure-reducing mattresses are primarily used to prevent pressure ulcers from
      occurring, in conjunction with other preventive measures, such as repositioning.
      The Vicair Academy Mattress, manufactured by Vicair BV and distributed by Gerald
      Simonds, uses Vicair's 'dry air' flotation system to offer maximum pressure and
      shear protection to patients who are at high risk of developing pressure ulcers.

PMID- 12048460
TI  - Gap in the level of support for mental health clients.

PMID- 12048461
TI  - Matrons are not going to solve all the problems.

PMID- 12048462
TI  - Cases involving nurses who abuse alcohol and drugs.

PMID- 12048463
TI  - Hirschsprung's disease: diagnosis and management in children.
AB  - Hirschsprung's disease is a congenital abnormality of the bowel that results in
      loss of peristalsis, and is one of the main reasons why an infant may require a
      stoma soon after birth. Various stages of surgery may be required to resect the
      affected part of the bowel, including formation and closure of the stoma.
      Following surgery, the perception of many families is that their child is now
      "normal" and that all previous problems of managing their child are now resolved.
      However, there are a variety of postoperative complications and issues relating
      to bowel control which can affect the child in the long term. This article looks
      at how potential postoperative long-term problems can be identified early, and
      thus minimized, by healthcare staff being aware of possible problems, taking a
      proactive approach to management and advising families about the issues involved.

PMID- 12048464
TI  - Legal aspects of consent 6: the mentally incapacitated adult.

PMID- 12048465
TI  - Does seclusion have a role to play in modern mental health nursing?
AB  - The seclusion of patients with mental health problems is a controversial and
      emotive subject, and is a practice that was condemned by the Ashworth Inquiry
      (Department of Health (DoH), 1992). Despite this condemnation, it is still widely
      practised today. Opinions on the practice of seclusion vary greatly.
      Consequently, there is a need to review the theoretical and empirical literature
      regarding the use of seclusion in order to gain an understanding of the current
      state of the knowledge base in this substantive and controversial area. This
      article systematically reviews research published between 1994 and 1999 and
      discusses the findings under three headings: staff/patient attitudes to
      seclusion; the alternatives to seclusion; and the efficacy of seclusion. The
      reviewed material shows that seclusion is seen as a legitimate intervention by
      some hospital staff, but is "dreaded" by mental health patients. What is also
      evident is that seclusion is largely believed to be effective and that no true
      alternatives to its use exist. However, there appears to be no formal means of
      determining what constitutes an effective intervention in the management of
      violent incidents. Implications for practice and areas for future study are also
      discussed.

PMID- 12048466
TI  - Assessing therapeutic intervention used by NHS Direct nurse advisers.
AB  - The National Service Framework for Mental Health has identified NHS Direct as a
      "new point of access" to appropriate mental health services. Mental health calls
      account for approximately 4% of all calls received by NHS Direct but raise the
      greatest level of anxiety among advisers and take twice as long to deal with as
      other calls. In order to provide adequate advice, it is essential to ensure nurse
      advisers can deal with this type of call. As a first step in meeting these needs
      this short research article reports on the types of interventions deployed by 18
      nurse advisers during role-plays with a mental health "client" expressing self
      harm.

PMID- 12048467
TI  - Neonatal intensive care: communication and attachment.
AB  - Birth has traditionally been recognized as a family-centred event where immediate
      exposure to the infant occurs and where the family begins, through direct
      contact, touch and voice, to form an attachment to the infant. In high-risk
      pregnancy and delivery, medical and technological advances distance the family
      from the birth event. This article describes some aspects of a research project
      with identified factors that facilitate and hinder family and mother attachment
      to the infant during periods of separation subsequent to premature delivery or
      other problems which require management in a neonatal intensive care unit (NICU).
      The project was exploratory. It involved observation of care, participation in
      care, individual unstructured interviews, focus group interviews and also use of
      Leske's (1986, 1991a,b) critical care family needs inventory, which was modified
      and responded to by family members (n = 109) in an attempt to quantify and
      validate their needs. Six constructs were derived from the inventory and then
      ranked by mothers (n = 100). The findings from this process were triangulated to
      observation and interview data in order to confirm factors that facilitate and
      hinder the process of attachment during family and mother-infant separation. The
      results of the study imply that when the family and mother are supported by an
      individualized approach to care and appropriate communication is used, attachment
      can be facilitated.

PMID- 12048468
TI  - Impact on professional carers of structured interviews with families.
AB  - This article describes a Swedish study exploring the impact of a structured
      assessment process on both family and professional carers. A total of 20
      professional carers conducted in-depth assessments with 245 family carers and
      were later interviewed about their experiences. The interviews indicated that the
      assessment process had provided valuable new insights and had challenged many
      existing preconceptions. They also afforded carers the opportunity to explore
      difficult emotional issues, suggesting the need to develop services to help
      carers deal with their feelings.

PMID- 12048470
TI  - Should there be random drug tests for nurses?

PMID- 12048469
TI  - Biogel Skinsense N: surgical glove management for latex allergies.
AB  - Healthcare staff with a high occupational exposure to latex gloves, such as those
      who work in the operating theatre, have a higher than average incidence of latex
      allergies. Certain patient groups are also known to be considered "high risk" for
      latex allergies. When wearing gloves, staff allergic to latex and those working
      with patients allergic to latex must wear latex-free gloves to protect themselves
      and their patients. Of all the different types of gloves available--examination,
      medical or diagnostic--surgical gloves have to meet the highest standards,
      offering both protection and comfort. However, latex-free surgical gloves have
      previously lacked some of the "comfort" qualities of natural latex. This article
      describes appropriate glove management for latex allergies and looks at the new
      generation of latex-free surgical gloves.

PMID- 12048471
TI  - Nurses will only get more pay if they take on new roles.

PMID- 12048472
TI  - Should Diane Pretty's husband be allowed to help her to die?

PMID- 12048473
TI  - Nurse who failed to recognize the serious condition of a patient.

PMID- 12048474
TI  - Improving diagnosis of malignant leg ulcers in the community.
AB  - Over 80% of all leg ulcer patients are cared for in the community by district and
      practice nurses, or by a relative who may or may not be adequately instructed or
      supervised. Many patients have never been referred for a specialist opinion,
      although their ulcers have been in existence for many years. This article
      discusses the current lack of community leg ulcer nurse specialists who could
      perform biopsies on non-healing wounds and thus reduce the amount of unnecessary
      hospital referrals. In turn this would speed referral times to hospital of
      patients with malignant leg ulcers.

PMID- 12048475
TI  - Violence: the duty of the employer and remedies by the employee.

PMID- 12048476
TI  - MMR and autism: an overview of the debate to date.
AB  - The ongoing controversial debate about the measles mumps rubella (MMR) vaccine
      and its links to regressional autism and specific bowel disorders appears to
      experience 'peaks and table troughs' of public interest correlated with specific
      media attention at any one time. It is not the intention of this article to
      either refute or substantiate the ongoing controversy, as this is obviously a
      scientific debate, but rather to offer an overview of the studies to date in the
      interest of helping practitioners in the frontline to engage in informed debate
      with concerned parents. The conclusions from this review stem from two major
      studies conducted by the Institute of Medicine (IoM, 2001) in the USA, and
      Medical Research Council (MRC, 2001) in the UK. Both conclude that although
      epidemiological studies so far do not support a link between MMR and autism,
      nonetheless the studies have been too imprecise to rule out the prospect of the
      vaccination being involved in a small number of cases, and the need for further
      research has been pointed out.

PMID- 12048477
TI  - Paediatric oncology research nursing: improving the service.
AB  - This article focuses on a paediatric oncology research nursing team, who
      highlighted potential gaps in their service provision because of the fact that
      both team members were part time. It discusses the processes undertaken once
      issues that were essential to maintain the smooth running of the service were
      highlighted. In today's climate of clinical governance, which facilitates the
      improvement and maintenance of high standards of patient care, nurses are
      required to demonstrate evidence of providing a high-quality service. By
      producing new documentation and consequently two standards, the oncology research
      team provided evidence of its endeavour to not only deliver a high level of care
      to children and families partaking in research studies, but also show written
      evidence of so doing. This evidence could be audited as a way of measuring
      service provision, to allow the team to make further developments and changes.

PMID- 12048478
TI  - Multiple sclerosis: the Treetops model of residential care.
AB  - This article describes the model of care that has been developed to promote
      empowerment, self-determination and hope for those with multiple sclerosis (MS)
      in residential care, while providing expert management of the clinical problems
      and resultant disability associated with MS. The model has been successful in
      improving the quality of life of MS patients in many tangible ways. Most
      significantly, the model has helped both staff and residents to realize the
      profound disability caused by MS can be managed more successfully if the unique
      clinical/psychosocial profiles of each person are explored, understood and
      accounted for in the management of their MS.

PMID- 12048479
TI  - The ACCESS model: a transcultural nursing practice framework.
AB  - As transcultural nursing is beginning to be a feature of health care in
      multiethnic and multicultural Britain, the need for transcultural health practice
      models is increasing. The focus of this article, the ACCESS model (Narayanasamy,
      1999), was developed to offer nurses a framework to deliver transcultural nursing
      care. Since its introduction there has been increasing interest about it from
      practitioners, nurse educators and students of nursing. The aim of this study was
      to ascertain the usefulness of the ACCESS model by a questionnaire study. In the
      institution where this study took place, pre- and post-registration nursing
      students are introduced to this model along with other models of transcultural
      health care. Participants (n = 166) who received transcultural healthcare
      education completed questionnaires with statements about the usefulness of this
      model. A significant number of participants found the model to be very useful
      with respect to its various features. The conclusion of this study is that the
      ACCESS model offers a useful framework for nurses implementing transcultural care
      practice. It appears that students and practitioners are interested in this model
      because of its practice implications.

PMID- 12048480
TI  - Transfoam Visco: evaluation of a viscoelastic foam mattress.
AB  - It is both a massive financial commitment and a huge financial decision to
      standardize mattresses in a large trust. It should only be undertaken after
      evaluation of the evidence of efficacy supplied by relevant companies, together
      with independent research and reports by healthcare professionals. In addition,
      evaluation of the equipment should be made by back care advisers, from a user
      safety viewpoint and physiotherapists, occupational therapists concerning
      rehabilitation. Ward-based nurses and patients need to assess equipment for
      comfort, ease of repositioning individual, and ability to relieve pressure. This
      article outlines the process by which a static mattress was evaluated for ease of
      movement, pressure relief and comfort by patients and healthcare professionals.
      The possible longevity of the mattress was considered as secondary relevance;
      however, cost-effectiveness and quality of product are essential in today's acute
      healthcare setting.

PMID- 12048481
TI  - Giving and serving are key elements in nursing.

PMID- 12048482
TI  - Stoicism does not make nursing a profession.

PMID- 12048483
TI  - People with learning difficulties need control.

PMID- 12048484
TI  - Maintaining and improving professional competence.

PMID- 12048485
TI  - Nutritional awareness of critically ill surgical high-dependency patients.
AB  - It has been recognized that malnutrition in hospital is a serious problem that
      may go undetected. There is growing evidence that early nutritional support in
      high-risk patients helps reduce postoperative complications; however,
      malnutrition is often diagnosed only once it is well established. This study
      showed that, both retrospectively and prospectively; there were no formal
      nutritional assessments of patients in a high-dependency unit (HDU), that time to
      feeding was generally within the recommended 5-7 day postoperative period, and
      that the most common form of supplementary feeding was total parenteral nutrition
      (TPN). Prospectively, the choice of supplementary feeding was dependent on the
      type of surgery and the individual patient's condition. Since this study was
      completed, a dietician has been allocated to the HDU and carries out formal
      nutritional assessments on a daily basis. Further research is required to assess
      the impact of the dietician on patient nutrition.

PMID- 12048486
TI  - What constitutes good care for people with dementia?
AB  - Person-centred care for people with dementia is an aspiration of both family and
      professional carers, but what constitutes person-centred care and how it can be
      achieved is less clear. This article describes a Swedish study in which in-depth
      interviews were completed with both family and professional carers of people with
      dementia with the purpose of exploring what they considered to be "best care".
      Important areas of similarity and difference were identified and the results
      suggest that both groups of carers need to work closely together if person
      centred care is to become a reality.

PMID- 12048487
TI  - Specialist nurses must understand clinical negligence litigation.

PMID- 12048488
TI  - Pregnancy anxieties and natural recognition in baby-switching.
AB  - Recent media reports in the USA of baby-switching at birth have caused anxiety
      for a number of maternity patients. Although alternative precautionary procedures
      are being implemented by hospitals to prevent baby-switching, ways to allay the
      maternity patient's anxiety must also be considered. While maternity patients can
      be expected to recognize their neonates, it is less clear how well they perform
      recognition under specified conditions. An American team of researchers noted
      postpartum mothers' anxiety levels and their natural cues to recognize crying
      sounds and garment smells of their babies as preventive measures against baby
      switching. An experimental study design was used to conduct this research.
      Participants completed a demographic form and Levin's pregnancy anxiety
      instrument, followed by three recognition challenges for hearing and smelling
      cues. Ten per cent of mothers reported anxiety about baby-switching, 65.9%
      recognized their babies from recorded crying, and 52.3% recognized their babies
      by smell. Mothers do have the natural ability to recognize the cries or smells of
      their babies, even when anxious about baby-switching. Educating new mothers,
      acknowledging their natural ability for baby recognition, and promoting the use
      of private rooms with same-room (couplet) care can serve as extra safeguards.

PMID- 12048489
TI  - Transjugular liver biopsy: method of choice for taking a biopsy.
AB  - A transjugular liver biopsy is a route of obtaining a biopsy of the liver for the
      diagnosis and management of patients with hepatic disease. In this article the
      author will demonstrate how a liver biopsy via the transjugular route is taken
      using X-ray guidance and will describe the method step-by-step as it is performed
      at the Royal Free Hospital. Finally, the indications and advantages of using this
      method will be considered. This article should increase awareness of what a
      transjugular liver biopsy is and inform the reader of how a tissue sample is
      taken, thus enabling further understanding of the procedure. It is concluded that
      the transjugular route of obtaining a liver biopsy enables a good size and
      quality of sample to be taken in a safe and effective manner with only one pass
      (one attempt) being required. This method involves minimal complications and has
      many advantages.

PMID- 12048490
TI  - Legal aspects of consent 7: young persons of 16 and 17 years.

PMID- 12048492
TI  - Inappropriate hospital admissions: patient participation in research.
AB  - Although political interest in reducing the number of inappropriate hospital
      admissions is mounting, methods for researching the rate of inappropriate
      admissions have several major limitations. Whereas traditional studies have
      tended to be predominantly subjective, more recent studies using clinical review
      instruments also have a number of limitations. Chief among these is the failure
      to consider the potential input of the individual patient. To illustrate some of
      the possible benefits of patient participation, this article cites findings from
      a study in Birmingham, which sought to involve individual older people in a
      research study into emergency hospital admissions.

PMID- 12048491
TI  - Improving self-management skills: a whole systems approach.
AB  - This article outlines the rationale behind an approach developed at the National
      Primary Care Research and Development Centre (NPCRDC) to improve patients'
      abilities to self-manage their conditions with the support of services provided
      by the NHS. The approach is systematic and requires involvement of patients in
      the development of information, changing access arrangements to health services
      and promoting a patient-centred approach to care. A programme of research and
      development is currently being undertaken at The University of Manchester by
      researchers based at NPCRDC to investigate the effectiveness of this approach.
      The evidence base for the strategy under investigation is discussed and proposals
      are made for the role of nurses as facilitators for the self-management agenda in
      the NHS.

PMID- 12048493
TI  - SuperSkin: the management of skin susceptible to breakdown.
AB  - Few studies have been undertaken in the area of skin protection, even though
      maintaining tissue viability in the event of incontinence, shear forces and the
      potential for exudate to macerate periwound areas remains a challenge for any
      nurse caring for patients. This article outlines and discusses the problems
      associated with overhydrated tissues and shear forces and the potential for
      SuperSkin liquid film dressing, marketed by CliniMed, to provide a solution.

PMID- 12048495
TI  - Let's lift district nursing out of the doldrums.

PMID- 12048494
TI  - Inadequate staffing leads to poor nursing care.

PMID- 12048496
TI  - The assessment and management of burns.
AB  - Each year many people seek medical advice or hospital treatment for burn or scald
      injuries. There is limited data on the number of burns patients seen in primary
      care, however a recent national survey suggested that there are 250,000
      presentations of burn injuries to primary care teams in the UK per year (National
      Burn Care Review, 2001). This article discusses the nursing management of burns
      in the community, outlining the initial assessment of the burns patient in terms
      of trauma management, and focusing primarily on those patients with non-complex
      burns. A full patient assessment incorporates the patient's general condition,
      the type, cause, depth and extent of the burn and the effects on the individual
      patient. Good patient management is an essential element of care and the focus of
      this is the management of pain, prevention of infection, provision of evidence
      based wound care and onward referrals as appropriate. However not all patients
      can be managed solely in the community and the nurse needs to know when to refer
      and to whom to refer. The article outlines the recommendations from the National
      Burn Care Review in terms of patient referral.

PMID- 12048497
TI  - Marie Curie nurses: enabling patients with cancer to die at home.
AB  - Marie Curie Cancer Care established its nursing service in 1958; however, the
      service has had little formal evaluation. This study aimed to describe and
      evaluate the care provided by Marie Curie nurse, and in particular to determine
      whether patients in their care remained and died at home. Two existing data sets
      were used: data on all patients referred to the Marie Curie Nursing Services in
      147 areas of England, Wales, Scotland and Northern Ireland for 26 months, and
      data on cancer death registrations in England. A request for a Marie Curie nurse
      was made for 26,632 patients, 97% of whom had cancer and 11% of whom lived alone.
      The amount of care provided varied enormously (<1 hour-2862 hours), although the
      vast majority of patients less than 300 hours of nursing care. Place of death was
      recorded for only half these patients; 94% died at home, 2.5% in a hospice, 2.3%
      in a hospital, 0.2% in a nursing home and 0.6% other. Home death was most often
      associated with patients receiving medication via a syringe driver, patients
      living with other people, patients with cancer, other than prostate cancer,
      shorter time between referral and death and younger age. The results lend support
      to the theory that the care given to patients in their homes by Marie Curie
      nurses facilitated home death for many patients. Services need to ensure that
      mechanisms are in place to achieve data collection. Rigorous prospective
      evaluation is needed in the future.

PMID- 12048498
TI  - Nutritional advice for obesity management and health.
AB  - Obesity is one of the fastest developing public health problems in the world and
      is associated with increased risks in morbidity and mortality. Any treatment
      programme for overweight and obese people should place equal importance on weight
      reduction and the maintenance of the weight loss. The National Service Framework
      for Coronary Heart Disease (Department of Health, 2000) identified the vital role
      of primary care teams in tackling overweight and obesity. The aim of this article
      is to give a basic overview of some of the issues and principles of weight
      management in primary care and to ensure nurses are equipped to provide good
      quality, evidence-based nutritional advice on weight management.

PMID- 12048499
TI  - Fungal nail infections: far more than an aesthetic problem.
AB  - Onychomycosis (fungal nail infection) is common and causes considerable
      discomfort and pain for many otherwise health patients. However, onychomycosis is
      especially prevalent in some patient groups seen regularly by community nurses
      (e.g. the elderly and people with diabetes, human immunodeficiency virus (HIV)
      infection or psoriasis). This article discusses the causes and types of
      onychomycosis, and examines in detail the various treatments available. Both the
      infection and its treatment can cause several clinical problems including drug
      interactions, difficulties with differential diagnosis and compromise of clinical
      outcomes. In particular, onychomycosis can undermine foot care in people with
      diabetes. The role of community nurses in treating and preventing onychomycosis
      is discussed.

PMID- 12048500
TI  - Community leg ulcer clinics vs home visits: which is more effective?
AB  - District nurses manage the care of the majority of patients with leg ulcers, but
      there have been reports of variations in the practice and effectiveness of
      treatment provided by district nurses (Audit Commission, 1999). Evidence-based
      health care aims to promote clinical and cost-effective care/treatment through
      the explicit, conscientious, and judicious use of the currently available best
      evidence from research to guide decisions (Sackett et al, 1996). Following the
      method of Griffiths (2002), a mini-systematic review was undertaken, to find out
      whether leg ulcer clinics provide more effective treatment to patients with leg
      ulcers than care provided in patients' homes by district nurses. Five databases
      were searched to find valid randomised controlled trials (RCTs) or systematic
      reviews to answer the question. The search was supplemented by hand searching of
      relevant publications. Only one trial met the inclusion criteria of the review.
      Although it concluded that leg ulcer clinics delivered improved outcomes the
      evidence provided was limited due to the comparison treatment being outdated,
      inadequate information regarding costs, and that as a relatively small isolated
      RCT it provided insufficient evidence to answer the question.

PMID- 12048501
TI  - Health and society in Finland: public health nurses' daily practice.
AB  - The role of public health nursing in Europe is changing as an ageing population
      and increasing social exclusion make new demands on health and social services.
      The purpose of this study was to describe how Finnish public health nurses (PHNs)
      practise in their daily work in order to meet the needs of this changing society.
      The knowledge base of the PHNs' work strongly emphasised experiential knowledge.
      However, on a theoretical level, medical knowledge dominated their work. The
      target of the PHNs' work was most frequently an individual, and perspectives of
      population or community were less common. The methods used in interactions with
      clients were participatory and empowered individuals to enhance their own health,
      and multiprofessional collaboration focused on joint decision-making and working
      towards the shared health goals of the client. However, PHNs need to employ a
      more reflective approach to their daily practice and take a more active role as
      an influential person in community and policy level.

PMID- 12048502
TI  - Tuberculosis: the silent epidemic.

PMID- 12048503
TI  - Are we using the users?

PMID- 12048504
TI  - An audit of pressure ulcer incidence in a palliative care setting.
AB  - This article reports a continuous audit of pressure ulcer incidence within a
      specialist palliative care unit over 2 years. Details of every patient admission
      were considered (542 patients). Of these, 26.1% were admitted with pressure
      ulcers while 12.0% developed pressure damage during their stay. The retrospective
      audit looked at the ulcers developing in the unit and found these patients were
      older, stayed 12 days longer and more of them died than the average for all
      patients admitted to the unit. In total, 95.3% were accurately assessed at 'high'
      or 'very high' risk using the Waterlow (1985) Pressure Sore Risk Assessment Tool
      and 89.2% of ulcers were Grade 1 or 2 measured using the Stirling Pressure Sore
      Severity Scale (Reid and Morrison, 1994). Of all developing ulcers, 78.4% were
      sacral and the position of the tumour, as well as comfort and positioning
      difficulties were considered most often responsible. Despite this knowledge and
      many 'improvements' introduced, the incidence did not improve with superficial
      ulcers often developing in the last days of life.

PMID- 12048505
TI  - The palliative care needs of people with intellectual disabilities: a case study.
AB  - This article describes a case study that aimed to consider the unique needs of a
      client who has intellectual disabilities and a terminal illness. Data collection
      included semi-structured interviews with the client and professionals involved in
      his care. Five broad sets of themes emerged from these interviews. Although these
      are not unique to the rapidly evolving field of palliative care, they are less
      familiar within the specialism of intellectual disabilities, i.e. difficulties
      and delays around diagnosing the illness, consent issues, conflicts between the
      carers and the family, truth-telling, and the need for professional support.
      Professionals who work with a person with intellectual disabilities and a
      terminal illness need to be aware that special issues may arise. The effects of
      potential problems with comprehension and communication need to be assessed
      individually. A close collaboration between all professionals, carers, family and
      the client, and the mutual sharing of expertise, is essential to ensure the best
      possible care.

PMID- 12048506
TI  - A practice-based evaluation of a liquid barrier film.
AB  - In palliative care it is often the little things such as being comfortable that
      help to improve a patient's quality of life. When the opportunity arose in our
      hospice to take part in a practice-based evaluation of a product that promised to
      make patients more comfortable, we were pleased to take part. Our small-scale
      evaluation was part of a wider study of SuperSkin, a liquid barrier film designed
      to protect skin at risk of damage. Information was collected from the patient,
      patient's medical notes and the nursing staff - a patient daily diary record was
      used in addition to normal information recordings. We evaluated the efficacy of
      the product and found this liquid barrier film to have a positive effect in
      several ways. It appeared to assist in the healing of skin damaged by friction
      and shearing forces, and from excoriation from wound exudates, urine and faeces.
      In addition, it appeared to protect healthy, 'at risk' skin from the same
      problems.

PMID- 12048507
TI  - Culture, palliative care and multiculturalism.
AB  - The frequently asked question, 'Why do minority ethnic groups not access
      palliative care?' needs closer analysis. This article sets out to revisit the
      context and principles of palliative care and discuss why palliative care
      services are not accessed equally by all cultural groups in western, particularly
      UK, society. The conceptual basis of culture, together with cultural diversity,
      will be discussed to foster greater understanding of multiculturalism with a view
      to offering recommendations for the provision of culturally sensitive palliative
      care. These recommendations will seek to be challenging but realistic, both for
      practitioners providing such care and for educationalist disseminating
      'knowledge'. I will highlight what I believe are the challenges of providing
      palliative care that is acceptable to minority ethnic groups based on personal
      experience and literature, and emphasize that these challenges should be seen as
      potential opportunities. It is hoped that this article will set a platform for
      honest and open discussion about the way forward in providing culturally
      sensitive palliative care for minority ethic groups. I will pose a challenging
      call to all members of minority ethnic groups to adopt a more proactive approach
      to their own care by preparing themselves to be in an influential position in
      palliative care provision through academic and clinical endeavours.

PMID- 12048508
TI  - Developing an integrated care pathway to manage cancer pain across primary,
      secondary and tertiary care.
AB  - Throughout the palliative care journey, the patient encounters many different
      health professionals in a variety of settings so good channels of communication
      between these professionals is a prerequisite for successful continuity of care
      (Scottish Partnership Agency for Palliative and Cancer Care (SPA), 1994). Pain
      control has also long been documented as being ineffective and it has been
      indicated that pain affects up to 88% of cancer patients in the last year of
      their life (Addington-Hall and McCarthy, 1995). In order to attempt to resolve
      these important issues, a joint project was established between primary,
      secondary and tertiary care in the south sector of Glasgow to establish an
      integrated care pathway (ICP) for the management of chronic cancer pain. This
      article discusses how the joint project was successfully established, was
      instrumental in breaking down existing barriers across the traditional boundaries
      and developed a uniform system of assessing and managing chronic cancer pain with
      ICP documentation held in a patient-held record.

PMID- 12048509
TI  - [Automated analyser of organ cultured corneal endothelial mosaic].
AB  - PURPOSE: Until now, organ-cultured corneal endothelial mosaic has been assessed
      in France by cell counting using a calibrated graticule, or by drawing cells on a
      computerized image. The former method is unsatisfactory because it is
      characterized by a lack of objective evaluation of the cell surface and
      hexagonality and it requires an experienced technician. The latter method is time
      consuming and requires careful attention. We aimed to make an efficient, fast and
      easy to use, automated digital analyzer of video images of the corneal
      endothelium. METHODS: The hardware included a PC Pentium III ((R)) 800 MHz-Ram
      256, a Data Translation 3155 acquisition card, a Sony SC 75 CE CCD camera, and a
      22-inch screen. Special functions for automated cell boundary determination
      consisted of Plug-in programs included in the ImageTool software. Calibration was
      performed using a calibrated micrometer. Cell densities of 40 organ-cultured
      corneas measured by both manual and automated counting were compared using
      parametric tests (Student's t test for paired variables and the Pearson
      correlation coefficient). RESULTS: All steps were considered more ergonomic i.e.,
      endothelial image capture, image selection, thresholding of multiple areas of
      interest, automated cell count, automated detection of errors in cell boundary
      drawing, presentation of the results in an HTML file including the number of
      counted cells, cell density, coefficient of variation of cell area, cell surface
      histogram and cell hexagonality. The device was efficient because the global
      process lasted on average 7 minutes and did not require an experienced
      technician. The correlation between cell densities obtained with both methods was
      high (r=+0.84, p<0.001). The results showed an under-estimation using manual
      counting (2191+/-322 vs. 2273+/-457 cell/mm(2), p=0.046), compared with the
      automated method. CONCLUSIONS: Our automated endothelial cell analyzer is
      efficient and gives reliable results quickly and easily. A multicentric
      validation would allow us to standardize cell counts among cornea banks in our
      country.

PMID- 12048510
TI  - [Results of strontium-yttrium-90 for pterygia].
AB  - MATERIAL AND METHODS: [corrected] In the Institute of Radio-Oncology in Lucerne
      we reviewed the records of 75 patients with 97 pterygia in a retrospective study.
      All patients had the same number of fractions (4), the same single fraction dose
      (1250cGy) and the same total dose (5000cGy). The operation technique used was the
      bare sclera technique. Patients were treated following three different concepts.
      The first group was treated prior to the operation, 1 fraction weekly, at least 2
      months before operation. The second group was treated postoperatively, also one
      fraction weekly, immediately after operation. The third group received 2
      fractions prior to and 2 fractions following operation. RESULTS: We observed only
      2 out of 97 (2%) recurrences in the second group. Because of their clinically
      inactive behavior these two cases required no further treatment. Three patients
      showed teleangiectasia as a moderate reaction. As a severe complication we
      observed one ulcus corneae, which was successfully treated with a lamellar
      keratoplasty, for a complication rate of 1%. CONCLUSION: Beta irradiation has
      proved to prevent pterygium recurrence. Severe late complications after excision
      and B-irradiation may partly be caused by other factors than irradiation alone.
      But it seems unequivocal that there is a relation with the high single-dose
      procedure of more than 2200cGy or re-irradiation. Fractionation must therefore be
      used.

PMID- 12048511
TI  - [Diagnostic approach for acquired and isolated third cranial nerve palsy: 18 case
      reports].
AB  - PURPOSE: The aim of this work was to establish a clinical diagnostic flow chart
      for third nerve palsy. MATERIAL AND METHODS: [corrected] We report a series of 18
      patients with third nerve palsy seen at the department of ophthalmology in the
      Marseille North Hospital between 1997 and 1999. All patients had a complete
      clinical examination and were classified into four clinic types. An etiological
      diagnosis was given in all cases after a systematic approach, including first
      intention MRI. RESULT: Three patients presented abnormal pupil reflex secondary
      to an aneurysm diagnosed by carotid angiography; the MRI was pathological in two
      cases. The 15 other patients had pupil sparing. Among them, eight patients had a
      total external involvement secondary to diabetes mellitus; the MRI suggested an
      ischelic origin in four cases (50%) showing nuclear infarctus. In seven cases the
      external involvement was incomplete secondary to multiple etiologies:
      demyelinating illness, traumatic lesions, orbital tumor, metastasis or myasthenia
      gravis. The MRI contributed to diagnosing four cases. CONCLUSION: The MRI must be
      systematically used in all the patients with isolated third nerve palsy, except
      for patients with pupil sparing associated with total external involvement.
      Ischemic etiology was the rule: simple clinical surveillance is proposed, total
      spontaneous regression being the norm.

PMID- 12048512
TI  - [Corneal asphericity in myopes].
AB  - PURPOSE: To study the variations of corneal asphericity in a population of myopic
      patients. METHODS: One hundred consecutive myopic patients were included in this
      study. The EyeSys videokeratoscope was used to assess the corneal topography of
      these patients seeking refractive surgery. We compared the results of cycloplegic
      refractions with the values of the corneal asphericity and mean central
      keratometry. RESULTS: Mean corneal asphericity was -0.09. Eighty per cent of the
      myopic patients had a prolate corneal contour, whereas 20% had an oblate corneal
      contour. No significant relationship was found between the corneal asphericity
      value and the mean keratometry value or the mean refractive error. CONCLUSION:
      The mean corneal asphericity in our myopic population was -0.09. This is slightly
      more than previously reported data in similar studies. No statistically
      significant relationship was found between corneal asphericity, mean refractive
      error, and mean keratometry.

PMID- 12048513
TI  - [Ophthalmic manifestations of masticulatory system dysfunctions].
AB  - Temporomandibular joint dysfunctions may involve ophthalmic symptoms such as
      orbital pain, asthenopia, or anisocoria. These ophthalmic manifestations may be
      the first signs or the complications of masticatory system dysfunctions.
      Treatment of these ophthalmic symptoms begins with treatment of the
      temporomandibular joint dysfunctions.

PMID- 12048514
TI  - [Spontaneous clearing of the cornea with detachment of Descemets membrane].
AB  - Detachment of Descemet's membrane (DM) is a rare complication of cataract and
      glaucoma surgery. Although permanent corneal edema is the usual outcome of a
      large detachment, spontaneous clearing of the cornea may occur. CASE REPORT: A 55
      year-old man underwent trabeculectomy in 1991 under local anesthesia. One day
      later the cornea was edematous, with a large superior DM detachment curling
      inward in the anterior chamber, limited by a thin blood pigmented line. Two
      months after cornea had cleared, and remained clear for ten years, with 20/20
      visual acuity and intraocular pressure of 14mmHg. DISCUSSION: Small detachments
      of DM after surgery are not rare and usually reattach spontaneously. However,
      extensive detachment results in overlying corneal edema and may require surgical
      reapposition. In our case, the cornea cleared spontaneously in the absence of DM
      repositionning, as denuded corneal stroma may be covered by newly regenerated DM.
      Before any surgical repair of DM detachment, one should consider spontaneous
      clearing of the cornea as a possible outcome.

PMID- 12048515
TI  - [Posterior vitrectomy for dislocated nuclear fragments during
      phakoemulsification: incidence, risk factors and prognosis of postoperative
      retinal detachment].
AB  - INTRODUCTION: Dislocated nuclear fragments during phakoemulsification are a well
      known complication. The treatment is often surgical, and serious complications,
      among which a retinal detachment may occur. The purpose of this study was to
      evaluate its incidence, risk factors, and prognosis. METHODS: This retrospective
      study included a consecutive series of 24 eyes undergoing posterior vitrectomy
      for dislocated nuclear fragments during phakoemulsification. The main outcome
      measures were the postoperative retinal detachment (incidence, risk factors,
      prognosis). RESULTS: Two retinal detachments occurred after vitrectomy, an
      incidence of 8%. In both cases, a significant inflammation of the anterior
      chamber and corneal decompensation were noted before vitrectomy. More than 50% of
      the nucleus was dislocated. Intraocular implant manipulation did not intervene in
      either case. Two tears occurred during vitrectomy in one case. The prognosis of
      the detachment, with proliferation, was poor in both cases. DISCUSSION: and
      conclusion: The high incidence of retinal detachment compares with that observed
      after phakoemulsification complicated by vitreous loss. Anterior segment
      deterioration, which compromises posterior segment visualization, and dislocation
      of more than 50% of the nucleus, that increases the risk of fragments falling on
      the retina during vitrectomy, may increase the occurrence of retinal detachment
      with a poor prognosis because of periretinal proliferation.

PMID- 12048516
TI  - [Corneal acid burning after facial peeling].
AB  - We describe the case of a 66-year-old woman who had previously undergone facial
      peeling and developed severe bilateral corneal burn due to direct contact
      Exopeel((R)) with her eyes. Despite medical treatment and an amniotic membrane
      graft, deep stromal opacity persisted in one eye.

PMID- 12048517
TI  - [Factors of recurrence of basal cell carcinomas of the eyelid].
AB  - Basal cell carcinomas of the eyelids can recur, although these recurrences are
      uncommon. In this retrospective study, all basal cell carcinomas treated at Reims
      Regional Hospital since 1985 were studied to determine the frequency of
      recurrence and the factors for recurrence. MATERIAL: and methods: All basal cell
      carcinomas treated at Reims Regional Hospital since 1985 were studied. A total of
      more than 200 patients had been operated on for basal cell carcinoma during this
      period. Those with orbital extension or a location on 2 eyelids were excluded.
      Epidemiological factors such as sex, age, tumor location, tumor size, and
      treatment were noted. Recurrences were uncommon, presenting in ten patients.
      These recurrences were studied in relation to the existing epidemiological data
      and the treatment provided, particularly the histological results. DISCUSSION:
      Basal cell carcinomas located on only 1 eyelid or 1 canthus can usually be
      treated with one surgical intervention. Extemporaneous histological study can
      preclude a local recurrence in most cases, but in some cases the condition may
      recur some years later. Factors favoring recurrence are difficult to determine.
      CONCLUSION: The authors report the number of recurrences after surgical treatment
      of basal cell carcinomas of the eyelids. The recurrences are relatively uncommon
      when the treatment has been done with extemporaneous histological examination of
      the resected edges. These recurrences arise particularly in relatively young
      patients with no other obvious risk factor.

PMID- 12048518
TI  - [Idiopathic polypoidal vasculopathy: 2 case reports].
AB  - Idiopathic polypoidal choroidal vasculopathy (IPVC), is a particular vascular
      abnormality of the inner choroid, composed of 2 components, a network of
      branching vessels of variable dimension, terminating in an aneurysm-like
      enlargement with sometimes episodic serosanguineous detachment of the retinal
      pigment epithelium and neurosensory retina. We report two cases of female
      patients with a peripapillary location of IPVC. None of the eyes had any drusen
      characteristic of age-related macular degeneration.

PMID- 12048519
TI  - [Cutaneous leishmaniasis of the lid].
AB  - We report 3 cases of patients presenting with lid cutaneous leishmaniasis in
      which clinical presentation was a true diagnostic problem. The patients were 3
      women aged 46, 36, and 60 years. The first patient presented with an ulceration
      of the superior eyelid that had been treated as chalazion. The second patient had
      a chronic lesion of the eyelid, present for 1 year, fitting the criteria for
      tuberculosis, syphilis, or sarcoidosis. The last patient had an erosive lesion of
      the internal canthus, which was suspicious of basal cell carcinoma. The presence
      of other cutaneous lesions and the chronic progression led to a biopsy for
      anatomopathology and parasitology analysis. These analyses confirmed the
      diagnosis of cutaneous leishmaniasis. The patients were then treated with
      antimony derivatives. Progression of the disease was marked by the appearance of
      a pigmented nonretractile scar. The different clinical characteristics,
      epidemiology, and treatment of this affection are reviewed.

PMID- 12048520
TI  - [Non penetrating filtering surgery, evolution and results].
AB  - Trabeculectomy is currently the standard filtration procedure for glaucoma
      surgical treatment. Despite several advantages over full-thickness procedures,
      trabeculectomy can be responsible for early postoperative complications related
      to sudden ocular decompression that can lead to hypotony with its sight
      threatening complications. Nonpenetrating glaucoma surgeries, namely
      viscocanalostomy and deep sclerectomy with external trabeculectomy, have been
      developed in recent years in order to improve the safety of conventional
      filtering procedures. The goal of these procedures is to reduce intraocular
      pressure (IOP) by enhancing the natural aqueous outflow channels, while reducing
      outflow resistance, attributed for 75% to the trabecular meshwork and for 25% to
      the outer wall of Schlemm's canal (SC) or tissue surrounding it. In these
      procedures, the anterior chamber is not opened so that complications related to
      full thickness procedures are mainly avoided. In the last few years,
      viscocanalostomy and deep sclerectomy with external trabeculectomy have become
      the most popular nonpenetrating filtering procedures. Both involve the removal of
      a deep scleral flap, the external wall of SC, and corneal stroma behind the
      anterior trabecula and Descemet membrane, thus creating a scleral lake. The
      aqueous humor leaves the anterior chamber through the intact trabeculodescemetic
      membrane and reaches the scleral lake, from where it will egress into different
      pathways. In viscocanalostomy, a high-molecular viscoelastic substance is
      injected into the ostia of the SC in order to enlarge the SC and its collector
      channels. In deep sclerectomy with external trabeculectomy, the main goal is to
      remove the inner wall of the SC and the adjacent trabecular layers involved in
      aqueous outflow resistance, while leaving the innermost trabecular layers intact
      so that the anterior chamber does not open during operation. Different surgical
      adjuvants designed to maintain the scleral lake open are commercially available.
      Retrospective and prospective published studies have reported similar midterm
      results with trabeculectomy and nonpenetrating filtering procedures in terms of
      IOP control, with fewer postoperative complications and better visual acuity
      recovery with the nonpenetrating procedures. This article reviews the current
      nonpenetrating surgical procedure techniques, their mechanism of action, and
      their outcome.

PMID- 12048522
TI  - [Coloboma of the optic disk complicated by macular NESD].

PMID- 12048521
TI  - [Drug delivery systems to target the anterior segment of the eye: fundamental
      bases and clinical applications].
AB  - The development of new drug delivery systems to target the anterior segment of
      the eye may offer many advantages: to increase the biodisponibility of the drug,
      to allow the penetration of drug that cannot be formulated as solutions, to
      obtain constant and sustained drug release, to achieve higher local
      concentrations without systemic effects, to target more specifically one tissue
      or cell type, to reduce the frequency of instillation and therefore increase the
      observance and comfort of the patient while reducing side effects of frequent
      instillation. Several approaches are developed, aiming to increase the corneal
      contact time by modified formulation or reservoir systems, or by increasing the
      tissue permeability using iontophoresis. To date, no ocular drug delivery system
      is ideal for all purposes. To maximize treatment efficacy, careful evaluation of
      the specific pathological condition, the targeted Intraocular tissue and the
      location of the most severe pathology must be made before selecting the method of
      delivery most suitable for each individual patient.

PMID- 12048523
TI  - [Primary signet ring cell carcinoma of the eccrine sweat gland in the eyelid.
      Immunohistochemical and ultrastructural study of a case].
AB  - We report a case of a 45-year-old woman who exhibited a primitive eccrine sweat
      gland carcinoma of the eyelid. Histological study showed cellular proliferation
      with an Indian file pattern and some signet ring cells with sialomucin secretion.
      Immunohistochemical study demonstrated these cells to be positive with the
      anticytokeratin, anti-EMA, anti-HMFG, antiestrogen receptor and antiprogesterone
      receptor antibodies. Ultrastructural study showed intracytoplasmic vacuoles with
      numerous microvilli at the apical side. Differential diagnosis with a metastasis
      from a mammary adenocarcinoma is difficult and a complete staging is necessary to
      confirm the primitive origin of the tumor. The behavior of this tumor is marked
      by locoregional recurrence.

PMID- 12048524
TI  - [Monitoring synthetic antimalarial treatment].

PMID- 12048525
TI  - Editorial: Systematic reviews of criminological interventions.

PMID- 12048526
TI  - Quality of life for patients with a personality disorder comparison of patients
      in two settings: an English special hospital and a Dutch TBS clinic.
AB  - INTRODUCTION: There are differing approaches to the management of people with a
      severe personality disorder in the UK and The Netherlands. Few comparative
      studies exist. This study describes the use of an adapted version of the
      Lancashire Quality of life profile as a patient based-outcome measure. METHOD: A
      cross-sectional sample of 37 patients was interviewed at each site. RESULT:
      Patients in the Dutch service reported a significantly higher quality of life
      which could not be explained by better objective circumstances. DISCUSSION: The
      data collected do not explain why the Dutch patients reported a higher quality of
      life. It is suggested that this finding was related to more extensive therapeutic
      activity and greater therapeutic optimism in the Dutch service. There is a need
      for critical scrutiny of the appropriateness of quality of life measures in
      offender patients before they are accepted for use as an outcome measure.

PMID- 12048527
TI  - The Forensic Inpatient Observation Scale (FIOS): development, reliability and
      validity.
AB  - INTRODUCTION: Re-offending, as a measure of success in forensic psychiatry, gives
      no information about other behaviours that may have changed. The development of
      the Forensic Inpatient Observation Scale (FIOS), an observation instrument to
      assess the non-offending functioning of forensic patients, is described. STUDY 1:
      In the first study the development of the initial item pool of the FIOS is
      described. This resulted in an instrument consisting of 78 items and seven
      scales. The internal reliability of the scales ranged from 0.78 to 0.91. The
      inter-rater reliability of the scales varied from 0.50 to 0.85 and the test
      retest reliability over a period of three weeks was high for most scales, ranging
      from 0.74 to 0.89. STUDY 2: In the second study the FIOS was developed further in
      another sample of forensic patients. This time exploratory factor analysis with
      Varimax rotation and post hoc reliability analysis were applied to determine the
      factor structure among the items. This resulted in an item pool of 35 items,
      among which six factors could be distinguished that closely resemble the factor
      structure of the FIOS in study one: (1) self-care, (2) social behaviour, (3)
      oppositional behaviour, (4) insight offence/problems, (5) verbal skills and (6)
      distress. Most items have high loadings on the factor they are assigned; 29 items
      have a loading of 0.60 or higher. The internal consistency of the scales ranges
      from 0.73 to 0.91 and the scales appear to be measuring independent constructs.
      Twenty-five out of the 35 items have an inter-rater correspondence of 90% or
      higher and 30 out of 35 items have an inter-rater correspondence of 87.5% or
      higher. The inter-rater reliability on the scale level, however, was somewhat
      less satisfying with correlations ranging from 0.50 to 0.69. DISCUSSION: It is
      argued that training the observers on a more regular basis will improve the inter
      rater reliability. There is some evidence for the convergent validity of the
      FIOS. The FIOS has some advantages over existing inpatient scales in that it is
      developed specifically for forensic patients, it does not particularly focus on
      axis 1 symptoms but includes oppositional behaviour and attitudes to offending.

PMID- 12048528
TI  - Psychosis and offending in British Columbia: characteristics of a secure hospital
      population.
AB  - INTRODUCTION: There is an increased likelihood of violence in the mentally ill
      although the risk is small. AIMS: The study aimed to ascertain the features in a
      secure hospital population that linked offending and mental illness. METHOD: A
      survey of patients in the high security hospital serving the province of British
      Columbia in Canada was carried out. Information on 175 mentally disordered
      offenders was extracted and included demographic data and specific
      characteristics of their offences, diagnoses and psychotic symptoms. RESULTS: The
      most prevalent offences were crimes of violence, but 39% of patients were not
      primarily violent offenders. Almost two-thirds (61%) had two or more diagnoses. A
      large majority of the patients were psychotic, schizophrenia being the most
      common diagnosis. There was a highly significant association between psychosis
      and violence, but the strength of the association was not increased by the
      presence of imperative hallucinations or delusions. The sample comprised various
      ethnic groups, one of which, Native Americans, was over-represented. However, no
      association was found between violent offending and ethnicity, or age or years of
      illness. DISCUSSION: The study replicates previous findings of the link between
      violent offending and psychosis, but not a specific link between violent
      offending and psychotic drive. A surprising finding was a lack of association
      between violent offences and substance misuse.

PMID- 12048529
TI  - A typology of adolescent delinquency: sex differences and implications for
      treatment.
AB  - BACKGROUND: This paper presents a test of Moffitt's theory (1990, 1993a)
      regarding offending trajectories as it applies to a population of adolescent
      offenders. This study is novel since few studies have empirically explored
      Moffitt's theory (1990, 1993a) with adolescent populations. METHOD: Data were
      collected retrospectively on 174 adolescents (101 males and 73 females), aged 13
      to 18. Three groups of offenders were identified based on a two-step cluster
      analysis: well adjusted, internalizing and externalizing groups. RESULTS:
      Consistent with Moffitt's theory, a sub-sample of offenders (externalizing group)
      engaged in more problem behaviours than the other offending groups. Additionally,
      female offenders in the internalizing group evidenced more psychopathology than
      males in this offending group as well as females in the other offending groups.
      Offending rates, in terms of offending frequency and variety of criminal
      offences, were not distinguished between the groups. CONCLUSIONS: These results
      provide evidence for Moffitt's theory (1990, 1993) regarding trajectories in
      adolescent offending. This study also provides support for the theory developed
      by Silverthorn and Frick (1999) regarding female offending. This was particularly
      evident in the rates of psychopathology evidenced by a sub-sample of adolescent
      females in the internalizing group.

PMID- 12048530
TI  - Editorial: Post-traumatic stress disorder as a bodily injury.

PMID- 12048531
TI  - Risk factors for adult male criminality in Colombia.
AB  - OBJECTIVES: This study sought to establish, in Colombia, the importance of
      factors alleged to be causes or correlates of adult criminality according to the
      published literature from other countries. METHODS: A comparison was made of
      arrested male offenders from ages 18 to 30 (n = 223) and similar community
      controls (n = 222) selected from five cities in Colombia as to their family
      background, exposure to abuse, family stressors, perceived care and history of
      childhood disruptive behaviour problems. RESULTS: Compared with neighbourhood
      controls from similar social classes, offenders were significantly more likely to
      report having had parents with less education, a mother under the age of 18 or
      over the age of 35 at time of birth, family members involved in crime,
      experiencing extreme economic deprivation, parental absence, family conflict,
      severe punishments, physical abuse, and maternal unavailability, rejection and
      lack of supervision. Prevalence of childhood disruptive behaviour problems was
      similar among offenders and controls. These findings appear to be independent of
      economic status, family size or type, birth order, or primary caregiver. Although
      the independent contribution of most of these factors is small, once all others
      have been controlled for, their cumulative effect is strong. CONCLUSIONS: The
      findings obtained in this Latin American setting do not support the generalized
      view that adult antisocial behaviour is necessarily preceded by a history of
      childhood behaviour problems. However, they do add evidence for the importance of
      family factors in the risk for adult criminality.

PMID- 12048532
TI  - A survey of female patients in high security psychiatric care in Scotland.
AB  - BACKGROUND: The State Hospital, Carstairs, is the sole high security psychiatric
      facility for Scotland and Northern Ireland. METHOD: This study compares the
      female (n = 28) and male (n = 213) patients resident there between 1992 and 1993
      using data derived from case-note reviews and interviews with patients and staff.
      RESULTS: Nearly three-quarters of both the male and female populations had a
      primary diagnosis of schizophrenia, and secondary diagnoses of substance abuse
      and antisocial personality disorder were common. Female patients were more
      frequently admitted from other psychiatric hospitals, had less serious index
      offences and more minor previous convictions, and were less likely to be subject
      to a restriction order. They had more often experienced depressive symptoms and
      had significantly greater histories of self-harm, physical and sexual abuse. At
      interview, nearly three-quarters had active delusions and over half had recently
      behaved in an aggressive manner. Almost 90% were said not to require the security
      of the State Hospital. CONCLUSIONS: It was concluded that mental illness and
      adverse social circumstances had combined to create a very disadvantaged group of
      women in high security psychiatric care in Scotland. As a group these women were
      inappropriately placed and their requirement was for intensive, rather than high
      security psychiatric care.

PMID- 12048533
TI  - Alcohol expectancies in convicted rapists and child molesters.
AB  - BACKGROUND: Previous findings suggest that cognitive factors and expectancies
      related to drinking can mediate subjective sexual arousal as well as aggression
      in men. Our aim was to investigate the drinking habits and alcohol-related
      expectancies that might predispose men to sexually aggress in two groups of
      sexual offenders. METHOD: Men convicted of rape (n = 10) were compared with men
      convicted of child molesting (n = 10) and with control subjects (n = 31). Current
      drinking habits (while not in prison) were assessed by self-report, and the
      extent of alcohol abuse was mapped by the Michigan Alcoholism Screening Test
      (MAST; Selzer, 1971). Cognitive expectancies related to alcohol use were explored
      by the standard Alcohol Expectancy Questionnaire (AEQ; Brown et al., 1980).
      RESULTS: The majority of the men who committed rape (70%) but only a third of the
      men convicted of child molesting were diagnosed with antisocial personality
      disorder. Alcohol abuse was common in men convicted of both rape and child
      molesting and the men convicted of rape expected significantly more positive
      effects from drinking than the control group. Both sex offender groups were the
      only groups to express significant alcohol-related cognitive expectancies linked
      to arousal and aggression. Expectancy patterns were directly linked to the
      antisocial personality characteristics. CONCLUSION: Alcohol abuse is common in
      men who commit both rape and child molesting. Heavy drinking and the anticipation
      of alcohol effects such as sexual enhancement, arousal and aggression may
      facilitate sexual aggression in offenders with antisocial personality disorder.

PMID- 12048535
TI  - Editorial - A state of siege: the English high security hospitals.

PMID- 12048534
TI  - Violence and the prior victim-stalker relationship.
AB  - INTRODUCTION: Previous research has suggested that stalkers who are ex-partners
      are more likely to be violent towards their victims than acquaintance or stranger
      stalkers. A survey was conducted in Britain of 95 individuals who had contacted
      the Suzy Lamplugh Trust because they were being stalked. METHOD: Eighty-seven of
      the victims were female and seven were male. They were put into three categories:
      ex-intimates, former acquaintances and strangers. RESULTS: Ex-intimates were the
      most aggressive of the three groups. Ex-partners were overall the most intrusive
      in their behaviour and were also the most likely to threaten and assault third
      parties as well as their principal victim. Stranger stalkers, however, were
      significantly more likely than ex-partners to be convicted of stalking-related
      offences. CONCLUSION: The experiences of our sample would suggest that being
      stalked carries a high violence risk. Across relational subtypes, over 40% of
      respondents had experienced physical assault, including attempted murder, sexual
      assault, or a combination of these acts.

PMID- 12048536
TI  - Homicide and schizophrenia: maybe treatment does have a preventive effect.
AB  - BACKGROUND: Persons with schizophrenia have been found to be at increased risk
      for homicide as compared with the general population. The increased risk may be
      associated with the implementation of the policy of deinstitutionalization.
      METHOD: Persons with schizophrenia who had committed or attempted homicide in the
      German state of Hessen from 1992 to 1996 and in the Federal Republic of Germany
      from 1955 to 1964 were compared. RESULTS: Schizophrenia increased the risk of
      homicide 16.6 times (95% CI 11.2-24.5) in the recent cohort and 12.7 times (95%
      CI 11.2-14.3) in the older cohort. These odds ratios are not statistically
      different. The lack of appropriate services for chronic high-risk patients and
      the non-use of mental health services by first episode, acutely psychotic
      patients were associated with homicide. CONCLUSION: There has been no increase in
      the risk of homicide among persons with schizophrenia since the implementation of
      the policy of deinstitutionalization. The examination of the recent period
      suggests that the provision of specialized long-term care to persons with
      schizophrenia who are at high risk for violent behaviour and the use of mental
      health services by acutely psychotic persons may reduce the risk of homicide.

PMID- 12048537
TI  - Casenote assessment of psychopathy in a high security hospital.
AB  - INTRODUCTION: There is now a large amount of data demonstrating the internal
      reliability and construct validity of the Hare Psychopathy Checklist (PCL/PCL-R)
      when used in the assessment of psychopathy in male forensic populations. It has
      well-established psychometric properties when scored following a review of
      collateral information and a subsequent interview. However, its internal
      reliability and factor structure, when casenote information alone has been used,
      have not been examined outside North America. METHOD: A sample of 89 patients
      from a British high security hospital, with the legal classification of
      psychopathic disorder, was scored retrospectively on the PCL-R from their medical
      files only. The psychometric properties of the PCL-R were analysed. Results The
      PCL-R ratings showed a high level of internal reliability. The factor structure
      was very similar to that found in Hare's North American sample of forensic
      psychiatric patients. DISCUSSION: The findings support the application of the PCL
      R, when scored using existing file data alone, to a British high security
      hospital population.

PMID- 12048538
TI  - Relapse prevention with sex offenders: practice, theory and research.
AB  - INTRODUCTION: Relapse prevention (RP) is now applied to sex offending. It has
      been questioned as to whether RP is worthwhile. This paper aims to evaluate this
      technique. THE ROCHESTER RP PROGRAMME: The purpose of the Rochester RP programme
      is to refine and strengthen skills gained in the prison department's sex offender
      treatment programme. The objective of the programme is to teach prisoners to
      recognize the chain of events leading up to their current offences and to
      practise strategies to interrupt this chain. THEORETICAL BASIS FOR RP: Stopping
      an undesired behaviour and maintaining abstinence are two different problems. RP
      aims to address the maintenance problems. At the centre of RP theory is a study
      of the conditions that can turn lapse into relapse. Yet RP has been criticized as
      a lot of jargon saying very little. Ward and Hudson criticize RP constructs and
      their interaction. Such debates have few implications for clinical work and most
      of the criticism flies in the face of clinical experience. RESEARCH BASIS FOR RP:
      Risk factors for sex offenders are being identified. Local evaluation of the
      Rochester programme suggests that prisoners do learn to identify risk factors and
      to develop coping strategies. As yet, however, there is no evidence as to whether
      RP works or not. DISCUSSION: A way to improve the efficacy of an RP programme may
      be to augment it with additional modules, e.g. behaviour therapy, drug treatment,
      continued work with the same prison staff and relaxation training. CONCLUSION: RP
      theory is sound in essence but suffers from an overlay of cumbersome vocabulary.
      Reliable research is emerging.

PMID- 12048539
TI  - The use of trial leave for restricted special hospital patients.
AB  - INTRODUCTION: For England and Wales, Section 17 of the Mental Health Act 1983
      allows for compulsorily detained patients to have trial leave (TL) between
      hospitals or from hospital to community to allow a period of testing readiness
      for a change in residency and/or legal status. The aim of this study was to
      document the use of TL for the largest sub-group of such patients within two
      discharge cohorts from one high security hospital and to test for correlates.
      METHOD: Data were collected from the special hospitals' case register for two
      Broadmoor Hospital discharge cohorts, 1984 and 1990-94, of offender patients with
      hospital orders under Home Office restrictions on discharge (Section 37/41).
      RESULTS: In 1984, only two of the 29 people leaving special hospital did so under
      trial leave arrangements, but by 1990 to 1994, 71% of restricted hospital order
      departures were under trial leave (92/130), a significant change in practice.
      Focusing on only the later cohort, women were disproportionately more likely to
      leave in this way. Trial leave was used more for patients with an index offence
      of homicide, similarly for violent offences but less so for sex offences. Nature
      of disorder did not have any bearing on the use of trial leave. Use of trial
      leave did not significantly shorten length of stay within the special hospital.
      CONCLUSION: Trial leave has become the most usual route out of special hospital,
      and is the departure route used almost exclusively for women patients, yet there
      appears to be no obvious advantage for the patient in shortening length of stay
      in high security. However, there is no way of knowing how long patients would
      have stayed had the option of trial leave not been available to them.
      Furthermore, no advantage for the public was found in the preferential use of TL
      for discharges to the community.

PMID- 12048541
TI  - No evidence of vertical transmission of HTLV-I in bottle-fed children.
AB  - The most frequent pathway of vertical transmission of HTLV-I is breast-feeding,
      however bottle fed children may also become infected in a frequency varying from
      4 to 14%. In these children the most probable routes of infection are
      transplacental or contamination in the birth canal. Forty-one bottle-fed children
      of HTLV-I seropositive mothers in ages varying from three to 39 months (average
      age of 11 months) were submitted to nested polymerase chain reaction analysis
      (pol and tax genes). 81.5% of the children were born by an elective cesarean
      section. No case of infection was detected. The absence of HTLV-I infection in
      these cases indicates that transmission by transplacental route may be very
      infrequent.

PMID- 12048540
TI  - Age-related seroprevalence study for St. Louis encephalitis in a population from
      Cordoba, Argentina.
AB  - A serological screening was performed in 615 individuals aged 0-87 years, living
      in the city of Cordoba, Argentina to study the relationship between antibody
      prevalence for the SLE virus and age. A 13.98% prevalence of neutralizing
      antibodies was obtained and its relation to age was significantly high (p =
      0.045). The highest seroprevalence was noted on individuals over 60 years old
      (>20%), whereas no subject under 10 was seropositive for this virus. Our results
      confirm that the agent is endemic in this area and neurological pathology studies
      should be performed on those individuals aged 60 since they represent the most
      susceptible group to SLE virus.

PMID- 12048542
TI  - Liver histology in co-infection of hepatitis C virus (HCV) and hepatitis G virus
      (HGV).
AB  - As little is known about liver histology in the co-infection of hepatitis C virus
      (HCV) and hepatitis G virus (HGV), HGV RNA was investigated in 46 blood donors
      with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6)
      and HCV isolated infection (n = 16). Besides staging and grading of inflammation
      at portal, peri-portal and lobular areas (Brazilian Consensus), the fibrosis
      progression index was also calculated. All patients had no symptoms or signs of
      liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients
      had mild liver disease and fibrosis progression index, calculated only in
      patients with known duration of infection, was 0.110 for co-infection and 0.130
      for isolated HCV infection, characterizing these patients as "slow fibrosers". No
      statistical differences could be found between the groups, although a lesser
      degree of inflammation was always present in co-infection. In conclusion co
      infection HCV / HGV does not induce a more aggressive liver disease, supporting
      the hypothesis that HGV is not pathogenic.

PMID- 12048543
TI  - Hepatitis C viral load does not predict disease outcome: going beyond numbers.
AB  - The analysis of 58 patients with chronic hepatitis C without cirrhosis and
      treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does
      not correlate with the histological evolution of the disease (p = 0.6559 for
      architectural alterations and p = 0.6271 for the histological activity index).
      Therefore, the use of viral RNA quantification as an evolutive predictor or
      determinant of the severity of hepatitis C is incorrect and of relative value. A
      review of the literature provided fundamental and interdependent HCV (genotype,
      heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and
      treatment variables (dosage, time of treatment, type of interferon) within the
      broader context of viral kinetics, interferon-mediated immunological response (in
      addition to natural immunity against HCV) and the role of interferon as a
      modulator of fibrogenesis. Therefore, viral load implies much more than numbers
      and the correct interpretation of these data should consider a broader context
      depending on multiple factors that are more complex than the simple value
      obtained upon quantification.

PMID- 12048544
TI  - Leptospirosis severity may be associated with the intensity of humoral immune
      response.
AB  - Leptospirosis severity may be increasing, with pulmonary involvement becoming
      more frequent. Does this increase result from an intense immune response to
      leptospire? Notice that renal failure, thrombocytopenia and pulmonary
      complications are found during the immune phase. Thirty-five hospitalized
      patients with Weil's disease had 5 blood samples drawn, from the 15th day to the
      12th month of symptoms, for ELISA-IgM, -IgG and -IgA specific antibody detection.
      According their 1st IgG titer, the patients were divided into: group 1 (n = 13)
      titer > 1:400 (positive) and group 2 (n = 22) titer < or =1:400 (negative). Early
      IgG antibodies in group 1 showed high avidity which may indicate reinfection.
      Group 1 was older, had worse pulmonary and renal function, and fever for a longer
      period than group 2. Throughout the study, IgG and IgA titers remained higher in
      group 1. In conclusion, the severity of Weil's disease may be associated with the
      intensity of the humoral immune response to leptospire.

PMID- 12048545
TI  - Evaluation of hemostasis disorders and anticardiolipin antibody in patients with
      severe leptospirosis.
AB  - A prospective study was designed to evaluate disorders of hemostasis and levels
      of anticardiolipin antibodies (ACL) in 30 patients with severe leptospirosis and
      acute renal failure (ARF) (ARF was defined as serum creatinine > or =1.5 mg/dL).
      The patients had been admitted to the Walter Cantidio University Hospital, Sao
      Jose Infectious Diseases Hospital and General Hospital of Fortaleza, Ceara, from
      August 1999 to July 2001. They all were male, with a mean age of 32 +/- 14 years
      and with clinical and laboratory diagnoses of ARF leptospirosis. The time elapsed
      between onset of symptoms and the first hemorrhagic manifestation was 9 +/- 4
      days. Bleeding was observed in 86% of the patients. Laboratory tests showed
      significantly high levels of urea (181 +/-95 mg/dl), fibrinogen, (515 +/- 220
      mg/dl), prothrombin time (13.3 +/- 0.9 seconds) and low platelet counts (69 +/-
      65 x 10(3)/mm3) on admission. There was no elevation in activated partial
      thromboplastin time or thrombin time. Levels of IgM and IgG ACL concentrations
      were significantly increased (p < 0.05) in leptospirosis patients when compared
      to control patients (28.5 +/- 32.4 vs. 11.5 +/- 7.9MPL U/ml and 36.7 +/- 36.1 vs.
      6.5 +/- 2.5 GPL U/ml), respectively. Vasculitis, thrombocytopenia and uremia
      should be considered important factors for the pathogenesis of hemorrhagic
      disturbances and the main cause of death in severe leptospirosis.

PMID- 12048546
TI  - Antigenic typing of Brazilian rabies virus samples isolated from animals and
      humans, 1989-2000.
AB  - Animal and human rabies samples isolated between 1989 and 2000 were typified by
      means of a monoclonal antibody panel against the viral nucleoprotein. The panel
      had been previously established to study the molecular epidemiology of rabies
      virus in the Americas. Samples were isolated in the Diagnostic Laboratory of the
      Pasteur Institute and in other rabies diagnostic centers in Brazil. In addition
      to the fixed virus samples CVS-31/96-IP, preserved in mouse brain, and PV-BHK/97,
      preserved in cell culture, a total of 330 rabies virus samples were isolated from
      dogs, cats, cattle, horses, bats, sheep, goat, swine, foxes, marmosets, coati and
      humans. Six antigenic variants that were compatible with the pre-established
      monoclonal antibodies panel were defined: numbers 2 (dog), 3 (Desmodus rotundus),
      4 (Tadarida brasiliensis), 5 (vampire bat from Venezuela), 6 (Lasiurus cinereus)
      and Lab (reacted to all used antibodies). Six unknown profiles, not compatible
      with the panel, were also found. Samples isolated from insectivore bats showed
      the greatest variability and the most commonly isolated variant was variant-3
      (Desmodus rotundus). These findings may be related to the existence of multiple
      independent transmission cycles, involving different bat species.

PMID- 12048547
TI  - Oral transmission of Chagas disease: importance of Trypanosoma cruzi biodeme in
      the intragastric experimental infection.
AB  - Oral transmission of Trypanosoma cruzi has been suspected when epidemic episodes
      of acute infection were observed in areas devoid of domiciled insect vectors.
      Considering that the distribution of T. cruzi biodemes differs in sylvatic and
      domestic cycles, results of studies on biodemes can be of interest regarding oral
      transmission. The infectivity of T. cruzi strains of different biodemes was
      tested in mice subjected to infection by the digestive route (gavage). Swiss mice
      were infected either with the Peruvian strain (Biodeme Type I, Z2b) or the
      Colombian strain (Biodeme Type III, Z1, or T. cruzi I); for control,
      intraperitoneal inoculation was performed in a group of mice. The Colombian
      strain revealed a similar high infectivity and pathogenicity when either route of
      infection was used. However, the Peruvian strain showed contrasting levels of
      infectivity and pathogenicity, being high by intraperitoneal inoculation and low
      when the gastric route was used. The higher infectivity of the Colombian strain
      (Biodeme Type III) by gastric inoculation is in keeping with its role in the
      epidemic episodes of acute Chagas disease registered in the literature, since
      strains belonging to Biodeme III are most often found in sylvatic hosts.

PMID- 12048548
TI  - Leishmaniasis in the genital area.
AB  - Two patients from the gold mines of Bolivar State, Venezuela, presenting
      cutaneous leishmaniasis in the genital region, an unusual location, are
      described. The first patient showed an ulcerated lesion of the glans penis.
      Leishmanin skin test was positive. A biopsy specimen revealed a granulomatous
      infiltrate containing Leishmania parasites. In the second patient, Leishmanin
      skin test was positive, HIV and VDRL were negative. Leishmania parasites were
      present in a biopsy of an ulcerated lesion in the scrotum, with an indurated
      base, infiltrative borders with an yellowish exudate. Patients were treated with
      meglumine antimoniate and the lesions healed.

PMID- 12048549
TI  - Anti-trypanosomal activity of pentacyclic triterpenes isolated from
      Austroplenckia populnea (Celastraceae).
AB  - Four pentacyclic triterpenes isolated from Austroplenckia populnea and four
      compounds of known anti T. cruzi or anti-malarial activity were tested. Of those
      triterpenes tested 20alpha-hydroxy-tingenone showed high activity, epikatonic
      acid was less active, while populnilic and populninic acids were inactive against
      the trypanosome of the subgenus Schizotrypanum tested. Benzonidazole, nifurtimox,
      ketoconazole and primaquine presented a remarkable dose-dependent inhibitory
      effect reaching practically to a total growth inhibition of the parasite at the
      end of incubation time. The trypanosome tested appear to be a suitable model for
      preliminary screen for anti T. (S.) cruzi compounds.

PMID- 12048550
TI  - Inflammatory paradoxical reaction occurring in tuberculosis patients treated with
      HAART and rifampicin.

PMID- 12048551
TI  - P system epithopes in Ascaris lumbricoides.

PMID- 12048552
TI  - Abundance of Mepraia spinolai in a Periurban zone of Chile.
AB  - Mepraia spinolai is a silvatic species of Triatominae which prefers microhabitats
      near to or in rock piles. It is also able to maintain similar or higher size
      populations near houses. The density of bugs in quarries near Santiago, Chile,
      differed within microhabitats and varied significantly within sites according to
      season. M. spinolai was not found in sites characterized by human perturbation of
      quarries. Our results confirm M. spinolai as a silvatic triatomine whose
      importance as a vector of Chagas disease will depend on contact with humans. This
      could occur if the habitats where populations of this species are found become
      exploited for the building of urban areas.

PMID- 12048553
TI  - Integrate study of a Bolivian population infected by Trypanosoma cruzi, the agent
      of Chagas disease.
AB  - A cross section of a human population (501 individuals) selected at random, and
      living in a Bolivian community, highly endemic for Chagas disease, was
      investigated combining together clinical, parasitological and molecular
      approaches. Conventional serology and polymerase chain reaction (PCR) indicated
      an active transmission of the infection, a high seroprevalence (43.3%) ranging
      from around 12% in < 5 years to 94.7% in > 45 years, and a high sensitivity
      (83.8%) and specificity of PCR. Abnormal ECG tracing was predominant in chagasic
      patients and was already present among individuals younger than 13 years. SAPA
      (shed acute phase antigen) recombinant protein and the synthetic peptide R-13
      were used as antigens in ELISA tests. The reactivity of SAPA was strongly
      associated to Trypanosoma cruzi infection and independent of the age of the
      patients but was not suitable neither for universal serodiagnosis nor for
      discrimination of specific phases of Chagas infection. Anti-R-13 response was
      observed in 27.5% only in chagasic patients. Moreover, anti-R13 reactivity was
      associated with early infection and not to cardiac pathology. This result
      questioned previous studies, which considered the anti-R-13 response as a marker
      of chronic Chagas heart disease. The major clonets 20 and 39 (belonging to
      Trypanosoma cruzi I and T. cruzi II respectively) which circulate in equal
      proportions in vectors of the studied area, were identified in patients' blood by
      PCR. Clonet 39 was selected over clonet 20 in the circulation whatever the age of
      the patient. The only factor related to strain detected in patients' blood, was
      the anti-R-13 reactivity: 37% of the patients infected by clonet 39 (94 cases)
      had anti-R13 antibodies contrasting with only 6% of the patients without clonet
      39 (16 cases).

PMID- 12048554
TI  - Domiciliation trend of Panstrongylus rufotuberculatus in Colombia.
AB  - The present paper presents evidence of the domiciliation of Panstrongylus
      rufotuberculatus in La Gardenia, Colombia through the collection of 2 unhatched
      eggs, 81 nymphs and 10 adults (4 males and 6 females), from 2 rural houses. The
      transmission risk indicators of Trypanosoma cruzi by P. rufotuberculatus in La
      Gardenia, were: domiciliary infestation 7.5%, density 2.35, colonization 66.6%,
      overcrowding 31.33, natural infection 4.6%, and relative infection 2.5%. These
      results and findings in Peru and Argentina, show that P. rufotuberculatus has a
      potential success in domiciliation and could some day become an alternate vector
      of American trypanosomiasis.

PMID- 12048555
TI  - Hepatitis a outbreak in a public school in Rio de Janeiro, Brazil.
AB  - From June 1 to July 1 1999, an outbreak involving 25 cases of hepatitis A
      occurred in a public school in Rio de Janeiro, Brazil. Since these cases were
      notified to the State Health Department, the National Reference Center for
      Hepatitis Viruses (CNRHV) was required to investigate the extent of hepatitis A
      virus (HAV) dissemination. Blood samples from all students were tested for IgM
      and total anti-HAV antibodies using a commercial enzyme-linked immunoassay
      (ELISA). At the same time, a questionnaire was completed in order to identify
      possible risk factors for HAV infection. The environmental investigation showed
      that there was no fecal contamination of the water supply. The epidemiological
      investigation demonstrated that almost 50% of this population was susceptible to
      HAV infection and probably person-to-person transmission was the principal mode
      of virus dissemination. In this situation, a massive vaccination campaign could
      control the HAV infection.

PMID- 12048557
TI  - A new species of Kritskyia (Dactylogyridae, Ancyrocephalinae) parasite of urinary
      bladder of Prochilodus lineatus (Prochilodontidae, Characiformes) from the
      Floodplain of the High Parana river, Brazil.
AB  - A new species of Kritskyia inhabits the urinary bladder of the "curimba",
      Prochilodus lineatus in the floodplain of the high Parana river. The new species
      resembles others members of Kritskyia in the following features: haptor lacking
      anchors and with 14 hooks marginal, posterior male copulatory organ non
      articulated with the accessory piece and vagina a sclerotized tube. However, it
      differs from the known species mainly by the shape of the copulatory complex.
      This is the third endoparasitic monogenean species reported from freshwater
      Neotropical fish.

PMID- 12048556
TI  - Ultrastructural, antigenic and physicochemical characterization of the Mojui dos
      Campos (Bunyavirus) isolated from bat in the Brazilian Amazon region.
AB  - The Mojui dos Campos virus (MDCV) was isolated from the blood of an unidentified
      bat (Chiroptera) captured in Mojui dos Campos, Santarem, State of Para, Brazil,
      in 1975 and considerated to be antigenically different from other 102 arboviruses
      belonging to several antigenic groups isolated in the Amazon region or another
      region by complement fixation tests. The objective of this work was to develop a
      morphologic, an antigenic and physicochemical characterization of this virus.
      MDCV produces cytopathic effect in Vero cells, 24 h post-infection (p.i), and the
      degree of cellular destruction increases after a few hours. Negative staining
      electron microscopy of the supernatant of Vero cell cultures showed the presence
      of coated viral particles with a diameter of around 98 nm. Ultrathin sections of
      Vero cells, and brain and liver of newborn mice infected with MDCV showed an
      assembly of the viral particles into the Golgi vesicles. The synthesis kinetics
      of the proteins for MDCV were similar to that observed for other bunyaviruses,
      and viral proteins could be detected as early as 6 h p.i. Our results reinforce
      the original studies which had classified MDCV in the family Bunyaviridae, genus
      Bunyavirus as an ungrouped virus, and it may represent the prototype of a new
      serogroup.

PMID- 12048558
TI  - Description of Pintomyia limafalcaoae and Pintomyia antioquiensis, two new
      species of phlebotomine sand fly (Diptera, Psychodidae) from the Colombian Andes.
AB  - Two new species of phlebotomine sand fly from Colombian Andes are described,
      belonging to the subgenus Pifanomyia of the genus Pintomyia. P. (P.) limafalcaoae
      sp. nov. for which both sexes are described, is assigned to the series pia while
      P. (P.) antioquiensis sp. nov., known only from the male, is included in the
      series verrucarum. The subgenus Pifanomyia is characterized and identification
      keys presented for the two new species.

PMID- 12048559
TI  - Neyraiella distinctus n. sp. (Oxyurida, Blattophilidae) parasite of nymphs of
      Gryllodes laplatae Sauss (Orthoptera, Gryllidae) in Argentina.
AB  - Neyraiella distinctus n. sp. was found parasitizing nymphs of the cricket
      Gryllodes laplatae Sauss in City Bell, Argentina. This species was characterized
      by having the excretory pore in the posterior end of the basal bulb, vulva
      protruding with one lip well developed in the 1/3 end of the body, anus of the
      female with wings, male with a single spicule without any sculpture, gubernaculum
      and bursa are absent, six pairs of genital papillae arranged in two preanal
      pairs, one adanal pair and three postanal pairs, and the tail appendage in both
      sexes was short and conic.

PMID- 12048560
TI  - Identification of human T-lymphotropic virus type I (HTLV-I) subtypes using
      restricted fragment length polymorphism in a cohort of asymptomatic carriers and
      patients with HTLV-I-associated myelopathy/tropical spastic paraparesis from Sao
      Paulo, Brazil.
AB  - Although human T-lymphotropic virus type I (HTLV-I) exhibits high genetic
      stability, as compared to other RNA viruses and particularly to human
      immunodeficiency virus (HIV), genotypic subtypes of this human retrovirus have
      been characterized in isolates from diverse geographical areas. These are
      currently believed not to be associated with different pathogenetic outcomes of
      infection. The present study aimed at characterizing genotypic subtypes of viral
      isolates from 70 HTLV-I-infected individuals from Sao Paulo, Brazil, including 42
      asymptomatic carriers and 28 patients with HTLV-1-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP), using restricted fragment length polymorphism
      (RFLP) analysis of long terminal repeat (LTR) HTLV-I proviral DNA sequences.
      Peripheral blood mononuclear cell lysates were amplified by nested polymerase
      chain reaction (PCR) and amplicons submitted to enzymatic digestion using a panel
      of endonucleases. Among HTLV-I asymptomatic carriers, viral cosmopolitan subtypes
      A, B, C and E were identified in 73.8%, 7.1%, 7.1% and 12% of tested samples,
      respectively, whereas among HAM/TSP patients, cosmopolitan A (89.3%),
      cosmopolitan C (7.1%) and cosmopolitan E (3.6%) subtypes were detected. HTLV-I
      subtypes were not statistically significant associated with patients' clinical
      status. We also conclude that RFLP analysis is a suitable tool for descriptive
      studies on the molecular epidemiology of HTLV-I infections in our environment.

PMID- 12048561
TI  - Molecular modeling approaches for determining gene function: application to a
      putative poly-A binding protein from Leishmania amazonensis (LaPABP).
AB  - The great expansion in the number of genome sequencing projects has revealed the
      importance of computational methods to speed up the characterization of unknown
      genes. These studies have been improved by the use of three dimensional
      information from the predicted proteins generated by molecular modeling
      techniques. In this work, we disclose the structure-function relationship of a
      gene product from Leishmania amazonensis by applying molecular modeling and
      bioinformatics techniques. The analyzed sequence encodes a 159 amino acids
      polypeptide (estimated 18 kDa) and was denoted LaPABP for its high homology with
      poly-A binding proteins from trypanosomatids. The domain structure, clustering
      analysis and a three dimensional model of LaPABP, basically obtained by homology
      modeling on the structure of the human poly-A binding protein, are described.
      Based on the analysis of the electrostatic potential mapped on the model's
      surface and conservation of intramolecular contacts responsible for folding
      stabilization we hypothesize that this protein may have less avidity to RNA than
      it's L. major counterpart but still account for a significant functional activity
      in the parasite. The model obtained will help in the design of mutagenesis
      experiments aimed to elucidate the mechanism of gene expression in
      trypanosomatids and serve as a starting point for its exploration as a potential
      source of targets for a rational chemotherapy.

PMID- 12048562
TI  - Charaterization of Leishmania major Friedlin telomeric terminus.
AB  - Here we have characterized Leishmania major (Friedlin) telomeric terminus (the
      very end) using recombinants obtained by a vector-adaptor cloning protocol. As in
      L. donovani, the last nine nucleotides of L. major terminus are 5'-GGTTAGGGT-OH
      3', differing from Trypanosoma cruzi and T. brucei terminus 5'GGGTTAGGG-OH 3',
      thus indicating that these sequences are genus specific. We have also made a
      comparative analysis between L. major and L. donovani telomere-associated
      sequences, and described a novel non-repeated telomeric associated sequence
      common to L. major low molecular weight chromosomal bands.

PMID- 12048563
TI  - Comparison of a recombinant-antigen enzyme immunoassay with Treponema pallidum
      hemagglutination test for serological confirmation of syphilis.
AB  - A recombinant-antigen enzyme immunoassay (EIA), BioSCREEN anti-Treponema
      pallidum, was compared favorably with the T. pallidum hemagglutination test, in
      the detection of specific antibodies in different groups of sera from patients
      with primary (n = 38), secondary (n = 10), early latent (n = 28) and congenital
      syphilis (n = 2), patients with leptospirosis ( n= 8), infectious mononucleosis
      (n = 7), hepatitis (n = 9), diabetes mellitus (n = 11), rheumatoid arthritis (n =
      13), leprosy (n = 11), tuberculosis (n = 9), HIV/Aids ( n= 12), systemic lupus
      erythematosus (n = 4), rheumatic fever (n = 3), old-persons (n = 9), pregnant
      women (n = 29) and blood donors (n = 164). The coincidence between them was
      95.1%. The sensitivity and specificity of the EIA were 93.3% and 95.5%,
      respectively. Fifteen serum specimens belonging to old-persons, pregnant women,
      blood donors, and patients with human leptospirosis, hepatitis, diabetes
      mellitus, tuberculosis and rheumatic fever gave false-positive results by
      Venereal Disease Research Laboratory and/or Rapid Plasma Reagin. The EIA can be
      used as alternative method for the serological confirmation of syphilis.

PMID- 12048564
TI  - Comparison of the proportion method with mycobacteria growth indicator tube and E
      test for susceptibility testing of Mycobacterium tuberculosis.
AB  - The aim of this study was to investigate the correlation between proportion
      method with mycobacteria growth indicator tube (MGIT) and E-test for
      Mycobacterium tuberculosis. Forty clinical isolates were tested. MGIT and E-test
      with the first line antituberculous drugs correlated with the proportion method.
      Our results suggested that MGIT and E-test methods can be routinely used instead
      of the proportion method.

PMID- 12048565
TI  - Activity and residual effect of two formulations of lambdacyhalothrin sprayed on
      palm leaves to Rhodnius prolixus.
AB  - The insecticidal activity and residual effect of two formulations of
      lambdacyhalothrin were evaluated with Rhodnius prolixus; laboratory and field
      tests were conducted in the State of Chiapas, Mexico. The results indicate that
      the lethal concentrations of the active ingredient of SC (LC50 = 2.37 and LC90 =
      8.5 mg, a.i./m2) were 4-8 times than those with the insecticide WP applied on R.
      prolixus bugs in palm leaves, a common building material for thatched roofs.
      Other investigators in South America recommended applying 30 mg a.i./m2 in porous
      materials; we obtained that the products WP and SC were 3.5 and 16 times more
      effective on palm leaves. Regarding the evaluation of the residual effects in
      field spraying, there was up to 15 months persistence after the application of WP
      in two doses (8.6 mg a.i./m2 and 3.752 mg a.i./m2) with SC. We consider R.
      prolixus highly susceptible to the employed pyrethroids; they could be used to
      control this vector in the state of Chiapas, Mexico.

PMID- 12048566
TI  - Oviposition attractancy of bacterial culture filtrates: response of Culex
      quinquefasciatus.
AB  - Oviposition attractants could be used for monitoring as well as controlling
      mosquitoes by attracting them to lay eggs at chosen sites. In the present study,
      culture filtrates of seven bacterial species were tested for their attractancy
      against gravid females of Culex quinquefasciatus. When their oviposition active
      indices (OAI) were studied, the culture filtrates of Bacillus cereus and
      Pseudomonas fluorescens exhibited oviposition attractancy (OAI = > 0.3) at 100
      ppm and the OAI were respectively 0.70 and 0.47. Culture filtrates of B.
      thuringiensis var. israelensis (wild type), B. t. var. israelensis (mutant) and
      B. sphaericus showed attractancy at 2000 ppm with OAI of respectively 0.71, 0.59
      and 0.68. However, the OAI of B. megaterium as well as Azospirillum brasilense
      was 0.13 (at 2000 ppm), which was less than 0.3 required to be considered them as
      attractants. When the oviposition attractancy of the bacterial culture filtrates
      were compared with that of a known oviposition attractant, p-cresol (at 10 ppm),
      the culture filtrates of B. t. var. israelensis (wild type) and B. cereus were
      found to be more active than p-cresol, respectively with 64.2 and 54.3%
      oviposition.

PMID- 12048567
TI  - Interaction between the intermediate host of Schistosomiasis in Brazil
      Biomphalaria glabrata (Planorbidae) and a possible competitor Melanoides
      tuberculata (Thiaridae): I. Laboratory experiments.
AB  - The biological control of Biomphalaria glabrata, intermediate host of Schistosoma
      mansoni, is one the accepted options to fight schistosomiasis. One of the most
      promising candidates to control B. glabrata is the snail Melanoides tuberculata,
      a potential competitor. However, the mechanisms of interaction between the two
      species are not clear. Our objective is to determine if M. tuberculata indeed
      compete with B. glabrata, using two laboratory experiments. In Experiment 1, we
      tested the effect of the presence of M. tuberculata on the fecundity and
      mortality rates of B. glabrata. In Experiment 2, we tested if there was a direct
      or indirect interaction between the two species. In Experiment 1, M. tuberculata
      was eliminated after the peak in reproductive activity of B. glabrata. In
      Experiment 2, B. glabrata produced more egg masses when raised with M.
      tuberculata. The conditions leading to this unexpected positive effect of M.
      tuberculata on the fecundity of B. glabrata need further clarification, but
      emphasize that detailed studies of the interaction between these species in the
      conditions of the local environment should be considered.

PMID- 12048568
TI  - Effect of antimalarial drugs on plasmodia cell-free protein synthesis.
AB  - A cell-free system from Plasmodium falciparum able to translate endogenous mRNA
      was used to determine the effect of artemisinin, chloroquine and primaquine on
      the protein synthesis mechanism of the parasite. The antimalarial drugs did not
      inhibit the incorporation of [3H] methionine into parasite proteins even at
      concentrations higher than the ones found to strongly inhibit the parasite
      growth. Results clearly indicate that these compounds do not have a direct effect
      on protein synthesis activity of P. falciparum coded by endogenous mRNA.

PMID- 12048569
TI  - Altered response of strain of Schistosoma mansoni to oxamniquine and
      praziquantel.
AB  - The susceptibility of a fourth generation Ouh strain (Paranapanema Valley, Sao
      Paulo, Brazil) of Schistosoma mansoni to oxamniquine (OXA) and praziquantel (PZQ)
      was studied. Ten groups of 13 female albino mice each were infected with 70
      cercariae per animal. These mice were medicated orally on the 50th day after
      infection. Five groups were given OXA doses of 0, 100, 200, 300 and 400 mg/kg
      (single doses) and the rest were treated with PZQ doses of 0, 100, 200, and 250
      mg/kg/5 days. Each group was sub-divided: 8 animals underwent perfusion after 15
      days treatment, 5 mice followed up for oviposition and their feces were tested
      every 15 days for miracidia hatching. The efficacy of the OXA doses of 100 and
      200 mg/kg was 66% and 91.4%, respectively and for the 100 mg/kg PZQ dose it was
      90.1%. The follow-up groups with 100 and 200 mg/kg of OXA and PZQ, 100 and 150
      mg/kg, showed that they re-established the oviposition after a period of 60 to 75
      days of treatment. The ED50 was 69.6 mg/kg OXA and 39.4 mg/kg PZQ. The results
      show the tolerance of the Ouh strain to a dose of 100 mg with both drugs and they
      appoint the need for a dose review during the follow up of the oviposition and in
      monitoring phenomena in the field.

PMID- 12048571
TI  - Nematode infections are risk factors for staphylococcal infection in children.
AB  - Nematode infection may be a risk factor for pyogenic liver abscess in children
      and we hypothesized that the immunomodulation induced by those parasites would be
      a risk factor for any staphylococcal infection in children. The present study was
      designed to compare, within the same hospital, the frequency of intestinal
      nematodes and Toxocara infection in children with and without staphylococcal
      infections. From October 1997 to February 1998, 80 children with staphylococcal
      infection and 110 children with other diseases were submitted to fecal
      examination, serology for Toxocara sp., evaluation of plasma immunoglobulin
      levels, and eosinophil counts. Mean age, gender distribution, birthplace, and
      socioeconomic conditions did not differ significantly between the two groups.
      Frequency of intestinal nematodes and positive serology for Toxocara, were
      remarkably higher in children with staphylococcal infections than in the non
      staphylococcal group. There was a significant correlation between intestinal
      nematodes or Toxocara infection and staphylococcal infection in children,
      reinforced by higher eosinophil counts and higher IgE levels in these children
      than in the control group. One possible explanation for this association would be
      the enhancement of bacterial infection by the immunomodulation induced by
      helminth infections, due to strong activation of the Th2 subset of lymphocytes by
      antigens from larvae and adult worms.

PMID- 12048570
TI  - Pseudomonas aeruginosa: study of antibiotic resistance and molecular typing in
      hospital infection cases in a neonatal intensive care unit from Rio de Janeiro
      City, Brazil.
AB  - This study had the objective of to analyze the demographic and bacteriologic data
      of 32 hospitalized newborns in an neonatal intensive care unit of a public
      maternity hospital in Rio de Janeiro city, Brazil, seized by Pseudomonas
      aeruginosa sepsis during a period ranged from July 1997 to July 1999, and to
      determine the antimicrobial resistance percentage, serotypes and pulsed field gel
      electrophoresis (PFGE) patterns of 32 strains isolated during this period. The
      study group presented mean age of 12.5 days, with higher prevalence of hospital
      infection in males (59.4%) and vaginal delivery (81.2%), than females (40.6%) and
      cesarean delivery (18.8%), respectively. In this group, 20 (62.5%) patients
      received antimicrobials before positive blood cultures presentation. A total of
      87.5% of the patients were premature, 62.5% presented very low birth weight and
      40.6% had asphyxia. We detected high antimicrobial resistance percentage to b
      lactams, chloramphenicol, trimethoprim/sulfamethoxazole and tetracycline among
      the isolated strains. All isolated strains were classified as multi-drug
      resistant. Most strains presented serotype O11 while PFGE analysis revealed seven
      distinct clones with isolation predominance of a single clone (75%) isolated from
      July 1997 to June 1998.

PMID- 12048572
TI  - Resistance of Plamodium falciparum to antimalarial drugs in Zaragoza (Antioquia,
      Colombia), 1998.
AB  - Plasmodium falciparum sensitivity to chloroquine (CHL), amodiaquine (AMO) and
      sulfadoxine/pyrimethamine (SDX/PYR) was assessed in vivo and in vitro in a
      representative sample from the population of Zaragoza in El Bajo Cauca region
      (Antioquia-Colombia). There were 94 patients with P. falciparum evaluated. For
      the in vivo test the patients were followed by clinical examination and
      microscopy, during 7 days. The in vitro test was performed following the
      recommendations of the World Health Organization. The in vivo prevalence of
      resistance to CHL was 67%, to AMO 3% and to SDX/PYR 9%. The in vitro test showed
      sensitivity to all antimalarials evaluated. Concordance for CHL between the in
      vivo and in vitro tests was 33%. For AMO and SDX/PYR, the concordance was 100%.
      We conclude that a high percentage of patients are resistant to CHL (in vivo). A
      high rate of intestinal parasitism might explain in part, the differences
      observed between the in vivo and the in vitro results. Therefore, new policies
      and treatment regimens should be proposed for the treatment of the infection in
      the region. Nationwide studies assessing the degree of resistance are needed.

PMID- 12048573
TI  - Aspects of the maintenance of the life cycle of Fasciola hepatica in Lymnaea
      columella in Minas Gerais, Brazil.
AB  - Fascioliasis is a parasitic disease of domestic ruminants that occurs worldwide.
      The lymnaeid intermediate hosts of Fasciola hepatica include Lymnaea columella,
      which is widely distributed in Brazil. A colony of L. columella from Belo
      Horizonte, MG, was reared in our laboratory to be used in studies of the F.
      hepatica life cycle, the intermediate host-parasite relationship and development
      of an anti-helminthic vaccine. In the first experiment 1,180 snails were exposed
      to miracidia of F. hepatica eggs removed from the biliary tracts of cattle from
      the State of Rio Grande do Sul. In the second and third experiments the snails
      were exposed to miracidia that had emerged from F. hepatica eggs from Uruguay,
      maintained in rabbits. The rates of infection in the first, second and third
      experiments were 0, 42.1 and 0% respectively. Over 15,806 metacercariae were
      obtained and stored at 4 degrees C. Four rabbits weighing 1.5 kg each were
      infected with 32-44 metacercariae and two with 200. Three rabbits begin to
      eliminate eggs of the parasite in the feces from 84 days after infection onwards.
      The biological cycle of F. hepatica in L. columella and the rabbit was completed
      within 124 days.

PMID- 12048574
TI  - Prevalence of Trypanosoma lewisi in Rattus norvegicus from Belo Horizonte, State
      of Minas Gerais, Brazil.
AB  - From April 1984 to March 1985, a Trypanosoma lewisi prevalence of 21.7% was found
      in 429 Rattus norvegicus trapped in Belo Horizonte, State of Minas Gerais,
      Brazil. The infection rates were higher in male and young rats and could be
      attributed to ecological and behavioral factors. T. lewisi was observed in rats
      measuring between 60 and 250 mm. Data about monthly T. lewisi infections
      throughout the year are presented for the first time in Brazil, with the highest
      prevalences observed in the warm-rainy season (October to March).

PMID- 12048576
TI  - Streblidae (Diptera) of phyllostomid bats from Minas Gerais, Brazil.
AB  - Eight streblid species were collected from eight phyllostomid bat species, from
      April to November 1997, at or near the Reserve "Parque Estadual do Rio Doce",
      Minas Gerais, Southeastern Brazil. In total, 48 specimens of streblid were
      removed from 57 phyllostomid bats. Most of batflies species were associated with
      a single species of the host, and only Paratrichobius longicrus (Miranda Ribeiro)
      and Trichobius joblingi Wenzel were recorded on three bat species. Trichobius
      lonchophyllae Wenzel represents a new record for the Brazilian Southeastern
      region.

PMID- 12048575
TI  - Variation of the oviposition preferences of Aedes aegypti in function of
      substratum and humidity.
AB  - Two Aedes aegypti (L.) populations were studied in the laboratory regarding the
      preference for three types of breeding sites, i.e., flasks containing only water,
      flasks with a plant and flasks with a stick. Each of these breeding units was
      placed in one cage and the choice of the oviposition sites was determined for
      individual females and three females per experimental unit at two humidity
      levels. Preference for ovipositing on the water surface was observed and varied
      according to experimental unit and humidity. Mean hatching of eggs in water
      surface was 46.6%. Experiments with three females showed a more marked difference
      than when only one female was used. Inter and intrapopulation variability
      regarding oviposition sites was observed. The discrimination between the
      different oviposition substrates, hatching in water surface and its implication
      for mosquito control are discussed.

PMID- 12048577
TI  - Trichomycete fungi (Zygomycota) associated with the digestive tract of Simulium
      goeldii Cerqueira & Nunes de Mello and Simulium ulyssesi (Py-Daniel & Coscaron)
      (Diptera: Simuliidae) larvae, in Central Amazonia, Brazil.
AB  - Trichomycete fungi are associated with digestive tract of black fly larvae. These
      fungi have not been studied in Brazil, knowing them and their relationship with
      black flies could be an alternative to control vector populations. The objectives
      of this study were to survey the Trichomycete fungi associated with larvae of
      Simulium goeldii and S. ulyssesi, and to determine if there is specificity and/or
      difference in the infection rates in these species. Black flies were collected in
      Central Amazonia, Brazil. Three genera of Trichomycetes were found: Harpella,
      Genistellospora and Smittium. All these fungi were common to both black fly
      species.

PMID- 12048579
TI  - The histopathology of the infection of Tilapia rendalli and Hypostomus regani
      (Osteichthyes) by lasidium larvae of Anodontites trapesialis (Mollusca,
      Bivalvia).
AB  - It is described the histopathology of the infection of Tilapia rendalli
      (Osteichthyes, Perciformes, Cichlidae) and Hypostomus regani (Osteichthyes,
      Siluriformes, Loricariidae) by lasidium larvae of Anodontites trapesialis
      (Mollusca, Bivalvia, Mycetopodidae). The larvae were encysted within the
      epidermis of the host, being surrounded by a thin hyaline membrane, 3-6 microm
      thick, of parasite origin. A proliferative host cell reaction did not occur. The
      histopathology of the infection shows that the lesions induced by the parasites
      are minimal. However, the numerous small lesions produced by the release of the
      larvae may provide optimal conditions for the infection by opportunistic
      pathogens, namely fungus, which may eventually cause the death of the host.

PMID- 12048578
TI  - Triatoma patagonica (Hemiptera, Reduviidae), a new host for Triatoma virus.
AB  - Previous authors demonstrated that Triatoma virus (TrV) is able to infect several
      species of triatomines when injected with viral inoculum obtained from its
      original host, T. infestans. Both vertical (transovarian) and horizontal (faecal
      oral) mechanisms of viral transmission were also described. In this paper we
      report the experimental TrV infection of a wild species from southern Argentina,
      T. patagonica. The inoculum consisted of clarified gut contents of infected T.
      infestans rubbed on the chicken skin whereupon T. patagonica individuals were
      fed. The results demonstrate that this is another potential host for the virus,
      and that the oral route is also effective for experimental interspecific
      infections.

PMID- 12048580
TI  - Isolation and identification of 9-methylgermacrene-B as the putative sex
      pheromone of Lutzomyia cruzi (Mangabeira, 1938) (Diptera: Psychodidae).
AB  - Lutzomyia (Lutzomyia) cruzi has been named as a probable vector of Leishmania
      chagasi in Corumba, Mato Grosso do Sul, Brazil. Taxonomically L. cruzi is closely
      related to the L. longipalpis species complex. Females of L. cruzi and L.
      longipalpis are morphologically indistinguishable and associated males must be
      examined carefully to confirm identifications. Chemical analysis hexane extracts
      of male L. cruzi has revealed the presence of a 9-methylgermacrene-B (C16), a
      homosesquiterpene (mw 218) previously shown to be the sex pheromone of one of the
      members of the L. longipalpis species complex.

PMID- 12048581
TI  - Oral susceptibility to yellow fever virus of Aedes aegypti from Brazil.
AB  - The oral susceptibility to yellow fever virus was evaluated in 23 Aedes aegypti
      samples from Brazil. Six Ae. aegypti samples from Africa, America and Asia were
      also tested for comparison. Mosquito samples from Asia showed the highest
      infection rates. Infection rates for the Brazilian Ae. aegypti reached 48.6%, but
      were under 13% in 60% of sample tested. We concluded that although the low
      infection rates estimated for some Brazilian mosquito samples may not favor the
      establishment of urban cycle of yellow fever in some parts of the country, the
      founding of Ae. aegypti of noteworthy susceptibility to the virus in cities
      located in endemic and transition areas of sylvatic yellow fever, do pose a
      threat of the re-emergence of the urban transmission of the disease in Brazil.

PMID- 12048583
TI  - Genomics and public health.

PMID- 12048584
TI  - Similarities in mortality patterns from influenza in the first half of the 20th
      century and the rise and fall of ischemic heart disease in the United States: a
      new hypothesis concerning the coronary heart disease epidemic.
AB  - The classic risk factors for developing coronary heart disease (CHD) explain less
      than 50% of the decrease in mortality observed since 1950. The transition
      currently under way, from the degenerative to the infectious-inflammatory
      paradigm, requires a new causal interpretation of temporal trends. The following
      is an ecological study based on data from the United States showing that in men
      and women an association between the age distribution of mortality due to
      influenza and pneumonia (I&P) associated with the influenza pandemic in 1918-1919
      in the 10-49-year age bracket and the distribution of CHD mortality from 1920 to
      1985 in survivors from the corresponding birth cohorts. It further shows a
      significant negative correlation (r = -0.68, p = 0.042) between excess mortality
      from I&P accumulated in epidemics from 1931 to 1940 (used as indicator for
      persistent circulation of H1N1 virus combined with vulnerability to infection)
      and the order of the beginning in the decline in CHD mortality in nine geographic
      divisions in the United States. In light of current biological knowledge, the
      data suggest that the 1918 influenza pandemic and the subsequent epidemics up to
      1957 might have played a determinant role in the epidemic of CHD mortality
      registered in the 20th century.

PMID- 12048585
TI  - [Survival analysis techniques].
AB  - Statistical methods known as survival analyses are useful for analyzing time
      related events, in which time from a benchmark event to an endpoint is the focus
      of interest. Survival analysis describes not only patient survival statistics (as
      suggested by the name), but also other dichotomous outcomes such as time of
      remission, time of breastfeeding, etc. This paper discusses survival analysis
      techniques, commenting and comparing their utilization, especially in the field
      of oncology. It also presents and discusses types of epidemiological studies and
      data sources to which this type of analysis is applied. The authors take into
      account the difference between hospital-based or clinical series and population
      based approaches. Interpretation of results is also discussed.

PMID- 12048586
TI  - [Politicized sexualities: AIDS activism and sexual orientation in Portugal].
AB  - This article analyzes how both the Portuguese state and civil society have
      addressed the AIDS issue, focusing on participation by the lesbian, gay,
      bisexual, and transsexual community (LGBT) in the struggle against AIDS. The
      article begins by describing the situation of LGBT individuals in Portugal during
      the 1990s, when the Portuguese LGBT movement emerged and grew, and then
      characterizes the evolution of HIV/AIDS in Portugal, analyzing the relationship
      between civil society and sexuality in general and the situation of the epidemic
      in the country in particular, considering key facts, nongovernmental
      organizations, and state initiatives. Special attention is given to the role
      played by LGBT organizations in the struggle against HIV. Finally, the article
      reflects on the future of the struggle against both AIDS and discrimination in
      the 21st century, considering recent events in the country and the guidelines
      recommended by international policies.

PMID- 12048587
TI  - [Prevalence of breast-feeding in Brasilia, Brazil].
AB  - This article presents the findings of a population-based cross-sectional survey
      carried out during a mass immunization campaign. A group of 3,305 mothers whose
      babies were 0 to 180 days old was selected by systematic sampling and interviewed
      with a pretested questionnaire. The prevalence of exclusive breast-feeding among
      0-15 day-old children was 62% (IC 95%: 58.5-65.3) and 12.8% (11.0-14.7), among
      151-180 day-old children. The average duration of exclusive breast-feeding was
      39.4 days. The prevalence of predominant breast-feeding was invariable along the
      age intervals showing a mean of 33.1% (31.4-34.7). The prevalence of partial
      breast-feeding among 0-15 day-old children was 4.5% (3.1-6.4) and 28.4% (25.8
      31.0) for the mentioned age groups. For maternal breast-feeding, the overall
      prevalence varied from 96.8% (95.8-97.7) to 70.9% (67.7-73.9). In conclusion,
      although the overall prevalence of breast-feeding in Brasilia is relatively high,
      the period that children are exclusively breast-fed is short.

PMID- 12048588
TI  - [Avoidable perinatal deaths and the environment outside the health care system: a
      case study in a city in Greater Metropolitan Rio de Janeiro].
AB  - This paper focuses on the role of environmental factors external to the health
      care system in the occurrence of perinatal deaths in maternity hospitals
      belonging to the local health system in a city in Greater Metropolitan Rio de
      Janeiro in 1994. Elements from the political and administrative context that
      contribute to an understanding of the relationship between failures in health
      care and structural deficiencies in these maternity hospitals were divided into
      four groups of variables: distribution of resources, spatial and temporal
      factors, organizational and managerial features, and action by interest groups.
      Semi-structured interviews were conducted. The study concluded that poor
      performance in four groups of variables may have contributed to perinatal
      mortality: distribution of resources was insufficient to provide quality in
      health care, especially in private maternity hospitals; there was no formal or
      informal regional or hierarchical organization of obstetric care in the city;
      Ministry of Health guidelines were ignored in all four maternity hospitals, while
      in three of the hospitals there were no admissions procedures and delivery and
      fetal follow-up listed in their own rules; and the level of actual participation
      was low.

PMID- 12048589
TI  - Spatial modeling using mixed models: an ecologic study of visceral leishmaniasis
      in Teresina, Piaui State, Brazil.
AB  - Most ecologic studies use geographical areas as units of observation. Because
      data from areas close to one another tend to be more alike than those from
      distant areas, estimation of effect size and confidence intervals should consider
      spatial autocorrelation of measurements. In this report we demonstrate a method
      for modeling spatial autocorrelation within a mixed model framework, using data
      on environmental and socioeconomic determinants of the incidence of visceral
      leishmaniasis (VL) in the city of Teresina, Piaui, Brazil. A model with a
      spherical covariance structure indicated significant spatial autocorrelation in
      the data and yielded a better fit than one assuming independent observations.
      While both models showed a positive association between VL incidence and
      residence in a favela (slum) or in areas with green vegetation, values for the
      fixed effects and standard errors differed substantially between the models.
      Exploration of the data's spatial correlation structure through the semivariogram
      should precede the use of these models. Our findings support the hypothesis of
      spatial dependence of VL rates and indicate that it might be useful to model
      spatial correlation in order to obtain more accurate point and standard error
      estimates.

PMID- 12048590
TI  - [Evaluation of operational conditions in the Adolescent Health Care Program, Rio
      de Janeiro].
AB  - This study focuses on conditions in the public health centers providing
      comprehensive care to the adolescent population in the city of Rio de Janeiro. A
      structured questionnaire was administered to the coordinators of 70 public health
      centers (70/78). Based on the data, the public health centers were stratified
      according to basic conditions for providing full care to adolescents. The authors
      developed a spatial study of the demographic concentration and main problems,
      producing thematic maps. Of the 49 public health centers that participate in the
      Adolescent Health Program, 12% were classified in "good" condition and 45% were
      considered "fair". Among the administrative regions with the highest
      concentration of adolescents, only six (6/17) were in good or fair condition. The
      authors conclude that to increase the effectiveness of the city's Adolescent
      Health Program it is necessary to improve the working conditions of their health
      staff, taking local health problems, the concentration of adolescents, and their
      demands for services into account.

PMID- 12048591
TI  - HIV/AIDS in South Africa: an overview.
AB  - This paper presents an overview of the development of HIV/AIDS in South Africa,
      taking into consideration the social context and analyzing the factors most
      likely to have influenced its spread as well as the societal response to it. The
      authors argue that macro factors such as social and political structures, in
      addition to behavioral ones, have combined to shape the course of the epidemic.
      Since various factors linked to social inequalities have combined to shape the
      pattern and growth of the HIV/AIDS epidemic in South Africa, it is inappropriate
      to focus on only one dimension in an attempt to combat the epidemic. Following
      the psycho-socio- environmental model, all potential contributing elements need
      to be addressed simultaneously. This calls for a true interdisciplinary and multi
      sectorial approach. It also requires great commitment as well as strong political
      will.

PMID- 12048592
TI  - [Insecticide resistance in Simulium populations (Diptera, Simuliidae)].
AB  - Populations of Simulium (Chirostilbia) pertinax Kollar, 1832 from Southern and
      Southeastern States of Brazil were analyzed for temephos susceptibility
      considering control historical information and possible resistance. In situ
      bioassays were carried out for populations from the states of Parana (Tibaji and
      Rolandia), Rio de Janeiro (Muriqui) and Sao Paulo (Barra do Una, Ilhabela and
      Morungaba). The populations were characterized as susceptible (S) or resistant
      (R) by submitting larvae in the last instars to an operational concentration
      (0.1ppm a.i./10min) of temephos (Abate 500E) as diagnostic. The possible
      mechanisms for the organophosphorus resistance development are discussed
      considering old and new control strategies.

PMID- 12048593
TI  - Suicide among young people in selected Brazilian State capitals.
AB  - This study analyzes suicide among young Brazilians (15-24 years old) in nine
      metropolitan areas. Mortality data for 1979-1998 were obtained from the Mortality
      Information System of the Ministry of Health. External causes are the main causes
      of death among youth, and suicide is the sixth most frequent of these causes. The
      distribution is heterogeneous, varying according to the social stratum, specific
      age group, sex, and means used to commit suicide. All cities analyzed showed
      increased suicide rates from 1979 to 1998 (from 3.5 to 5.0 per 100,000
      inhabitants 15-24 years old). Salvador and Rio de Janeiro had the lowest suicide
      rates, while Porto Alegre and Curitiba had the highest. The principal means used
      by youth to commit suicide were hanging, strangling, and suffocation (Porto
      Alegre), followed by firearms and explosives (Belo Horizonte).

PMID- 12048594
TI  - [Factors in training and participation in childbirth care by non-physicians].
AB  - This study aimed to characterize midwives according to current concepts among
      health professionals and to identify the ideological premises underlying
      proposals for their training. Data from interviews with nine midwives, nurses,
      and physicians were interpreted using discourse analysis. The resulting empirical
      categories were "The Situation of Maternity Care in Brazil", "The Ideal (or
      Necessary) Midwife and the Possible Midwife". When these empirical categories
      were interpreted, it was possible to "construct" an "emerging midwife" by
      dialectically overcoming the concept of "the ideal midwife".

PMID- 12048595
TI  - [Dental caries and socioeconomic conditions: a cross-sectional study among 18
      years-old male in Florianopolis, Santa Catarina State, Brazil].
AB  - The aim of this study was to assess the prevalence and severity of dental caries
      and need for treatment among 18 years-old males in Florianopolis, Southern
      Brazil. In addition, the associations between dental caries and socioeconomic
      conditions were tested. A cross sectional study was carried out. A random sample
      of 300, was selected from a list of Brazilian Army conscripts. Clinical data were
      collected according to World Health Organization criteria. Socioeconomic data
      (years of education of the subjects, their fathers and mothers and family income)
      were collected through interviews. The statistical significance of associations
      between socioeconomic indicators and dental caries prevalence were tested using
      the chi-square test whilst for severity of dental caries Mann-Whitney test was
      used. The prevalence of dental caries was 81% and the mean DMF-T was 4.5. The
      mean number of teeth that needed treatment was 1.2. Both dental status and
      treatment need were statistically significantly associated with socioeconomic
      indicators. Those with low levels of education and income experienced more
      disease and needed more treatment than those from high levels of education and
      income.

PMID- 12048596
TI  - [Why are children abused? A bibliographical review of the explanations for child
      abuse].
AB  - This article analyzes the factors related to child abuse that have been published
      in three of the main Brazilian pediatrics journals. The literature was assessed
      by content analysis. Fourteen studies were analyzed. The main explanatory factors
      were: (a) reproduction of violence; (b) family and psychological disorders and
      alcohol abuse; and (c) the structural or macro-social order. The authors conclude
      that prevention or intervention policies can be more successful if a
      theoretical/practical understanding is achieved, and that it is necessary to
      integrate each unique case with the knowledge based on care for thousands of
      families involved in child abuse both in Brazil and worldwide.

PMID- 12048597
TI  - [Childbirth and live newborns of adolescent and young adult mothers in the
      municipality of Feira de Santana, Bahia State, Brazil, 1998].
AB  - Data from the Brazilian Ministry of Health and the literature indicate that
      adolescents may be overrepresented in the prevalence of maternal morbidity and
      mortality and neonatal complications. This study focused on childbirth and live
      newborns among adolescent and young adult mothers in the municipality of Feira de
      Santana, Bahia, identifying risk factors for morbidity and mortality. A cross
      sectional cohort study was conducted based on data from the Information System on
      Live Births (SINASC) in the municipality in 1998, totaling 5,279 live births
      among adolescent (10 to 19 years) and young adult mothers (20 to 24 years).
      Variables were age, schooling, prenatal care, gestational care, form of delivery,
      and birthweight. The authors measured the association between maternal age and
      the child's birthweight, while controlling potential confounders. Some 21.6% of
      live births were to adolescent mothers, 51.2% of whom had not finished primary
      school; there was an association between the 10 to 16-year age bracket and
      incomplete primary schooling, lack of prenatal care, and low and insufficient
      birthweight as compared to the other age brackets; there was also a high rate of
      underrecording in the SINASC. The results suggest the need for specific measures
      focusing on the reproductive health of adolescents in the municipality.

PMID- 12048599
TI  - [Recording of venomous bites and stings by National Information Systems in
      Brazil].
AB  - This paper highlights the epidemiological surveillance of venomous bites and
      stings according to four national information systems: SINAN (National Databank
      of Major Causes of Morbidity), SINITOX (National Information System on
      Poisoning), SIH-SUS (Hospital Information System of the Unified Health System),
      and SIM (Mortality Information System). The authors conclude that each
      information system has specific characteristics and addresses different demands.
      Although they contain large amounts of data, even if combined they fail to
      reflect the real magnitude of disorders caused by venomous bites and stings in
      the country.

PMID- 12048598
TI  - [Epidemiology of schoolchildren's cognitive development in Jequie, Bahia State,
      Brazil: assessment procedures and general results].
AB  - This paper describes the methodology, applicability and utility of the Raven
      Progressive Matrix (Raven Test) and the Brazilian Intellectual Probe (TSI),
      comparing them with school achievement in a typical medium-size urban community
      of Northeastern Brazil. 388 schoolchildren (7-17 years old) were examined, with
      371 Raven tests applied. Only 231 TSIs were completed, since 106 students were
      illiterate. School grades were obtained for all participants. A questionnaire
      evaluating school resources, and teacher profiles was answered by 200 teachers.
      Raven and TSI test scores were highly correlated (r = 0.53, p < 0.001), but both
      correlated weakly with overall school grade (r = 0.22, p < 0.001 and r = 0.12, p
      < 0.07 respectively). For individual school grades, the Raven scores showed
      statistically significant correlation with all subjects, while the Brazilian TSI
      presented statistically significant correlation only with geography, history and
      sciences. Boys' mean scores were higher than girls' for both the Raven and the
      TSI Tests, but for the school grades girls performed better. In general, level of
      cognitive development was below that expected for children in the age-group
      analyzed.

PMID- 12048600
TI  - [Hospitalization due of infectious diarrhea in Rio de Janeiro State].
AB  - Diarrhea is an important cause of hospitalization among infants. There are many
      complex factors that influence hospital use: socioeconomic and cultural
      characteristics, access, medical needs, and supply. The objective was to measure
      hospitalization rates from diarrhea among infants in Rio de Janeiro in 1996 and
      the association with demographic, geographical, and clinical data comparing
      differentials between public/university and private/philanthropic hospital care
      under the Unified National Health System (SUS). The authors used data from the
      Hospital Information System. Private/philanthropic hospitals admitted
      approximately four times more children than public/university hospitals. Analysis
      shows that variation in age, length of hospital stay, and use of pediatric
      intensive care may reflect differences in physicians' practice styles. This may
      in turn influence the respective health care unit's capacity to prevent death
      associated with diarrhea. The authors conclude that it is necessary to continue
      the analysis of hospital utilization under the SUS due to implications for the
      cost and quality of pediatric care.

PMID- 12048601
TI  - [Dental caries and socioeconomic conditions in the State of Parana, Brazil,
      1996].
AB  - The aim of this research was to determine the correlation between dental caries
      and socioeconomic conditions in the State of Parana, Brazil. Caries prevalence
      was estimated for each city in the State by gathering data on the DMFT index (in
      12-year-old schoolchildren) supplied by the State Health Department. Official
      socioeconomic data for the municipalities were also presented. Ordinary least
      squares regression analysis was performed, and significant correlation
      coefficients were observed between the dental caries index and various social
      development indicators. Maps highlighting the overlapping areas with poor
      outcomes for most of these variables were presented. The results showed a
      significantly lower DMFT index in cities with fluoridated water supply and a
      negative correlation between the caries index and the proportion of households
      with running water in cities with fluoridated water supply. This observation
      highlights the importance of fluoridated drinking water for the prevention of
      dental caries and as a measure to reduce the impact of socioeconomic inequalities
      on the prevalence of tooth decay.

PMID- 12048602
TI  - Evaluation of waist circumference to predict general obesity and arterial
      hypertension in women in Greater Metropolitan Belo Horizonte, Brazil.
AB  - This study examined the capacity of waist circumference (WC) to identify subjects
      with overweight (BMI >/=25) and obesity (BMI >/=30), in agreement with
      internationally recommended levels of action. Data were obtained from 791 women,
      15-59 years old. After identifying overweight and obesity according to WC values,
      sensitivity and specificity were calculated to verify whether WC could be a good
      risk predictor for hypertension. Associations were tested by linear regression
      and logistic regression, controlling for confounding. WC cut-off points of 80cm
      and 88cm correctly identified 89.8% and 88.5% of women with overweight and
      obesity, respectively. Abdominal obesity (WC >/=88cm) was statistically
      associated with hypertension in the multivariate analysis (OR = 2.88; 95% CI:
      1.77-4.67). Hypertension was identified with a sensitivity of 63.8% and 42.8%,
      and with a specificity of 68.0% and 83.3%, for WC >/=80 and >/=88, respectively.
      The proposed cut-off points for abdominal obesity can potentially distinguish
      individuals at risk for future obesity, but has only moderate power to predict
      individuals with high blood pressure.

PMID- 12048603
TI  - Risk and prognostic factors for diarrheal disease in Brazilian infants: a special
      case-control design application.
AB  - The aim of this study was to examine the effect of demographic, socioeconomic,
      environmental, maternal reproductive, dietary, and nutritional variables on
      diarrhea risk and prognosis using a hierarchical framework. A case-control study
      of children aged 0-23 months in Greater Metropolitan Porto Alegre was conducted
      during the peak season for diarrhea in 1987-1988. Three groups were investigated,
      with 192 children each. The first group included hospitalized children with an
      episode of acute diarrhea complicated by moderate to severe dehydration. The
      second group included children with acute mild diarrhea without signs of
      dehydration who were identified in the same neighborhood as hospitalized cases.
      The third group consisted of controls without diarrhea. Mothers were interviewed
      by trained interviewers using a standardized questionnaire. Data analysis
      included a hierarchical approach to control for confounding, using conditional
      logistic regression. Comparison of the three groups aimed to identify risk
      factors for diarrhea complicated by dehydration, prognostic factors for
      dehydration, and risk factors for mild diarrhea. Low birth weight, stunting, and
      lack or breastfeeding acted simultaneously as risk and prognostic factors for
      diarrhea.

PMID- 12048604
TI  - Cross-cultural measurement equivalence of the Revised Conflict Tactics Scales
      (CTS2) Portuguese version used to identify violence within couples.
AB  - Following a previous evaluation of concept, item and semantic equivalences, this
      paper assesses the measurement equivalence between a Portuguese version of
      Revised Conflict Tactics Scales (CTS2) and the original instrument conceived in
      English. The CTS2 has been widely used to tap violence between couples. An intra
      observer reliability evaluation involved 165 replications carried out within a 24
      48 hour period. Kappa point-estimates were above 0.75 for all scales except
      sexual coercion. The analysis of internal consistency concerned 768 subjects with
      complete sets of items. Kuder-Richardson-20 estimates ranged from 0.65 to 0.86.
      Results were similar to those found in the original instrument in English for the
      negotiation, psychological aggression and physical violence scales, yet not so
      for the sexual coercion and injury scales. Factor analysis identified factors
      with a recognizable correspondence to the underlying dimensions, although a few
      inconsistencies were detected. For the assessment of construct validity (n = 528)
      associations between the instrument's scales were evaluated, as well as the
      relationships between violence and putative underlying dimensions. Overall, the
      findings suggest that the version can be used in the Brazilian context, although
      further investigation should be carried out to unveil some important remaining
      issues.

PMID- 12048605
TI  - [Reproductive health and risk as perceived by low-income Brazilian men].
AB  - Studies in the field of reproductive health discuss existing gaps in traditional
      research models, which neglect not only social and cultural aspects but also
      ethical and philosophical ones. Such aspects cut cross over the definition of
      essential themes for reproductive health research, like sexuality, reproduction,
      and gender. The search for connections between the two disciplines (Social
      Science and Public Health) relates to how people and social groups limit and deal
      with the risks they face. In this study, we analyze the perception of risk in
      reproductive health among a group of low-income men from Rio de Janeiro. The
      group was interviewed during a study on male contraception. The objective was to
      identify the situations and contexts from which the problem (and the contents
      ascribed to it) emerge. One can conclude from the interviews that there is a risk
      hierarchy which is modified according to cultural values and relational,
      institutional, and social contexts.

PMID- 12048607
TI  - [Prevalence and severity of dental caries and treatment needs in small Brazilian
      counties].
AB  - The aim of this study was to assess the prevalence and severity of dental caries
      and the need for dental treatment among schoolchildren in two small Brazilian
      counties. WHO criteria (1986) for the diagnosis of dental caries and treatment
      needs were adopted. All 6 to 12-year-old schoolchildren in both Sao Joao do Sul
      (n = 803) and Treviso (n = 382), both in the State of Santa Catarina, were
      invited to participate in the study. The response rate was 96% and 91%
      respectively. All kappa values for inter- and intra-examiner agreement were
      greater than 0.62. Prevalence of caries among 6 to 12-year-old children was 62.1%
      in Sao Joao do Sul and 63.6% in Treviso. Mean DMF-T for the same age group was
      1.91 and 1.84 respectively. Need for treatment was high in both counties, however
      it was mainly related to simple clinical procedures. In conclusion, prevalence of
      dental caries among 6 to 12-year-old schoolchildren was lower in the two small
      counties studied than in other small communities in Brazil. The need for
      treatment was great, but it was related to simple clinical procedures. In
      addition, there is a need to collect further data from small towns to develop an
      oral health strategy appropriate to such areas.

PMID- 12048606
TI  - [Work in the prison system: a study of correctional officers in Greater
      Metropolitan Salvador, Brazil].
AB  - A cross-sectional study was conducted to identify possible associations between
      working conditions and health among correctional officers in Salvador, Bahia,
      Brazil. The study used a stratified proportional random sample of 311 individuals
      who answered a non-identifiable self-applied questionnaire. The following results
      were obtained by logistic regression: (a) psychologically inadequate workplace,
      insufficient basic work conditions, no leisure time, lack of sports practice,
      >/=nine years working in the prison system, excessive work hours, >/=48 hours
      work/week, and inadequate organizational conditions at work were associated with
      minor psychological disorders; (b) lack of specific training, female gender,
      >/=48 hours work/week, psychologically inadequate workplace, no leisure time, and
      lack of sports practice were associated with persistent stress, (c) age >/=45
      years, >/=nine years working in the prison system, excessive work hours, lack of
      sports practice, inadequate basic and organizational work conditions, and minor
      psychological disorders were associated with health complaints.

PMID- 12048608
TI  - [Vertical stratification of phlebotomine sandfly fauna (Diptera, Psychodidae) in
      a primary non-flooded forest of the Central Amazon, Amazonas State, Brazil].
AB  - Studies on the vertical stratification of phlebotomine sandfly fauna were
      conducted in a non-flooded primary forest at a Tropical Forest Experimental
      Station of the National Institute of Amazonian Research from October 1998 to
      March 1999. CDC light traps were placed at one, 10, and 20 meters above ground. A
      total of 2,859 sandflies were captured, belonging to the Lutzomyia (99.93%) and
      Brumtomyia (0.07%) genera, represented by 38 species. In the Lutzomyia gender,
      the most frequent sub-gender was Nyssomyia (43.4%), followed by Psychodopygus
      (22.8%). Lutzomyia umbratilis, L. anduzei, L. rorotaensis, L. trichopyga, and L.
      olmeca nociva predominated at one meter above ground, while L. davisi, L.
      infraspinosa, L. umbratilis, L. trichopyga, and L. anduzei predominated at 10
      meters. L. anduzei, L. tuberculata, L. dendrophyla, and L. dreisbachi were the
      most abundant species at 20 meters. L. umbratilis, which appeared at all three
      levels of vertical stratification, has great epidemic significance as a vector of
      Leishmania (Viannia) guyanensis.

PMID- 12048609
TI  - [Neonatal screening for hemoglobinopathies: a pilot study in Porto Alegre, Rio
      Grande do Sul, Brazil].
AB  - This study was conducted to establish the frequency of hemoglobinopathies among
      newborns undergoing screening tests for metabolic diseases at the University
      Hospital (Hospital de Clinicas) in Porto Alegre, Rio Grande do Sul, Brazil.
      Testing for abnormal hemoglobins was performed by isoelectric focusing
      electrophoresis on agarose gel with blood obtained by heel stick and applied to
      filter paper. For confirmatory testing of abnormal neonatal screening, a
      venopuncture blood sample was obtained from the infant and parents and then
      submitted to hemoglobin electrophoresis on cellulose acetate at pH 8.6 and
      citrate agar at pH 6.2. A total of 1,615 subjects were studied: 20 samples showed
      the Hb S pattern and six samples showed Hb C. Thus, frequency of the sickle cell
      gene was 1.2% and that of the Hb C gene was 0.4%, regardless of race or origin.
      These data suggest that the inclusion of universal neonatal screening for
      hemoglobinopathies in the ongoing projects for the detection of phenylketonuria
      and congenital hypothyroidism has many advantages and should be considered in
      health programs.

PMID- 12048610
TI  - [Work and psychological distress among bank tellers in Rio de Janeiro].
AB  - This article discusses key relations between psychological distress and bank
      tellers' working conditions in various bank offices in Rio de Janeiro. Different
      theoretical models are discussed: stress, the psychodynamics of the work, and the
      psychopathology of the work. The aim of this case study was to elucidate the role
      of the work process as a source of psychological distress among tellers in a
      large bank company. Analysis of the work process with its variability and
      difficulties showed that two highly stressful situations are 1) discrepancies in
      the amounts of money counted at the teller's window and 2) customer complaints or
      insults directed against the teller. Such situations arise from the work
      organization that forces tellers to streamline or skip security rules and blames
      them for "discrepancies" in the till. The form of work organization also fails to
      support tellers in answering customer demands appropriately. The context of low
      wages and major transformations favoring workers' isolation generates insecurity
      over their future, viewed as lack of individual recognition. An approach to
      tellers' actual working conditions allowed for an understanding of stress factors
      and their determinants.

PMID- 12048611
TI  - [Spatial distribution of tegumentary leishmaniasis in the city of Rio de
      Janeiro].
AB  - The authors analyze the historical and spatial determinants of the implantation,
      persistence, and spread of cutaneous leishmaniasis in the municipality of Rio de
      Janeiro and the links between the disease and the organization of urban space and
      occupation processes on the periphery of the city beginning in the early 20th
      century through the 1980s. A pattern of outbreaks that was restricted and
      spatially discontinuous but sequenced was observed and seen to be linked to a
      dynamic process of urban real estate appreciation, comprising a large endemic
      area for cutaneous leishmaniasis. An analysis of the occupation and organization
      of urban space in the so-called Western Zone of Rio de Janeiro was conducted,
      considering new functions of spatial elements expressed through changing work
      relations, land use, and land value. Urbanization of the area produced the
      necessary conditions to intensify an endemic pattern of well-defined outbreaks
      where human mobility and the work process increased contact between susceptible
      individuals and vectors. Analysis showed spatial units with differentiated risk
      levels.

PMID- 12048612
TI  - [Critical aspects of dengue control in Brazil].
AB  - Dengue is now the main reemerging disease in the world. In the absence of an
      efficacious preventive vaccine and effective etiologic treatment and
      chemoprophylaxis, the only vulnerable link for reducing dengue transmission is
      the mosquito Aedes aegypti, its principal vector. There are many difficulties in
      combating this mosquito in large and medium-sized cities. The complexity of
      contemporary urban life generates factors that facilitate the mosquito's
      proliferation and constraints on the reduction of its infestation rates. The
      objectives of dengue control should be based on available scientific and
      technical knowledge. Thus, while it is not possible to avoid dengue in areas
      infested with A. aegypti, it is possible to prevent major epidemics by improving
      epidemiological surveillance, and it is both possible and feasible to reduce the
      disease's case fatality from the current 5 to 6% to some 1% in the severe forms.
      The elaboration and execution of strategic plans for the organization of medical
      care for suspected dengue cases have proven to be a highly useful instrument to
      reduce case fatality both in other countries and in some cities of Brazil.

PMID- 12048613
TI  - [What is the source of mycelial fungi in expressed human milk?].
AB  - The authors characterized the genera of mycelial fungi found in samples of
      expressed human milk received through home collection by the Human Milk Bank of
      the Instituto Fernandes Figueira in Rio de Janeiro. A total of 821 samples of
      expressed human milk were taken randomly from bottles collected at home by the
      milk donors themselves and were investigated for molds, yeasts, and mesophilic
      microorganisms. The analyses showed the occurrence of molds and yeasts in 43
      (5.2%) of the samples, with counts reaching 103CFU/ml. Some 48 strains of
      mycelial fungi were identified by standard laboratory techniques, including:
      Aspergillus Niger group (6.3%), Aspergillus sp. (4.2%), Paecilomyces sp. (12.6%),
      Penicillium sp. (60.4%), Rhizopus sp. (2.0%), and Syncephalastrum sp. (14.5%).
      The authors discuss the importance of donor hands' asepsis prior to collecting
      human milk.

PMID- 12048615
TI  - [Instructions from teaching hospital maternity wards to parents concerning the
      sleeping position of newborns].
AB  - The prone sleeping position has been causally linked to sudden infant death
      syndrome (SIDS). This survey aimed to determine whether maternity hospitals in
      Brazil were promoting the prone sleeping position for newborns. Information was
      also collected on SIDS prevention messages. The study adopted a multicenter
      collaborative approach in hospitals with training in pediatrics, using
      questionnaires. Correctly completed questionnaires were received from 55
      hospitals. The number of deliveries/year varied at the hospitals from 240 to
      11,000 (median 2,750). The majority of hospitals encouraged the lateral (side)
      sleeping position in the normal care nurseries (44.4%) and at discharge (67%). In
      conclusion, the majority of hospitals surveyed are not promoting the supine
      sleeping position or any other intervention for SIDS prevention, although verbal
      information is provided to parents about breastfeeding (100%), immunization
      (100%), and smoking (85%).

PMID- 12048614
TI  - [Prevalence of dental fluorosis in school children from Marinopolis, Sao Paulo].
AB  - The purpose of this study was to determine the frequency and severity of dental
      fluorosis in 5 to 12 and 15 year-old school children in the city of Marinopolis,
      Sao Paulo, Brazil, with the purpose of obtaining a baseline data for the
      monitoring dental fluorosis in this population. All of the school children in the
      both sexes, in the mentioned ages, enrolled in educational institutions and
      having the pre-requirement condition of to live in Marinopolis from their birth
      were involved, totaling 320 school children. The exams were made by one examiner
      previously calibrated to use the Dean Index. According to the results, the
      frequency of dental fluorosis in the studied group was 17.2%, however just
      considering the fluorosis levels that determine aesthetic compromising (mild,
      moderate and severe), this percentile was 7.19%. The predominant level was the
      very mild (10.0%) followed for the mild (5.3%), moderate (1.3%) and severe
      (0.6%). Concluding that the dental fluorosis in the studied population doesn't
      constitute in a problem with wide dimensions, however, subsequent studies are
      necessary in the attempt of identifying the causes of moderate and severe
      fluorosis cases.

PMID- 12048617
TI  - [The effect of psychosocial factors on risk of dementia].
AB  - In the etiology of dementia several genetic and various environmental factors are
      assumed to interact. Most epidemiological studies on risk factors have focused on
      "constitutional" factors like age, sex, birth order, dementia in the family and
      "life style" factors like smoking and alcohol consumption. Only few studies have
      investigated the role of psychosocial factors at work and during leisure time on
      the risk to develop dementia. Our paper gives a systematic review of all
      published results of controlled studies about psychosocial risk factors. A
      positive association has been observed between dementia and living alone, having
      no close social ties, not participating in social and leisure activities, and
      never having married. Recent studies have found that Alzheimer's disease in
      particular is negatively associated with diversity of activities and intensity of
      intellectual activities and positively associated with psychosocial inactivity,
      unproductive working style, living with a dominant spouse and with physical
      inactivity.

PMID- 12048618
TI  - [Locomotion and depression. Clinical and physiological aspects of gait
      alterations in Parkinson's disease and major depression].
AB  - BACKGROUND: Behavioral disturbances of patients with major depression manifest in
      various motor domains and are relevant for differential diagnosis, therapeutic
      interventions, as residual symptoms and possibly early manifestation of
      Parkinson's disease. Alterations of gait as the main component of locomotion are
      a clinically well-known motor phenomenon of depressed patients. Therefore,
      pathophysiology of gait disturbances, different methods to analyze gait and
      empirical findings in patients with major depression are summarized. METHODS: The
      current literature was examined including information of manufacturers, Medline,
      PubMed, PsychLIT and Excerpta Medica. Findings in healthy subjects, in
      Parkinson's disease, and in major depression are discussed in detail regarding
      specificity and clinical relevance. RESULTS: Kinematic analysis of gait
      regulation by videography, ultrasound, opto-electronic measures reveals
      information about disturbances in central nervous motor programming. Only few
      studies exist about quantitative data of gait alterations in patients with major
      depression. Results indicate disturbances in functions of the basal ganglia.
      CONCLUSIONS: Analysis of gait using modern technology yields information about
      cortical and subcortical dysfunctions. Empirical findings in major depression
      need further investigation regarding their relevance as residual symptoms, as
      response predictors, and as risk factors for manifestation of Parkinson's
      disease.

PMID- 12048619
TI  - [Vagus nerve stimulation. A potential therapy for chronic/recurrent depression?].
AB  - Vagus Nerve Stimulation (VNS) is since the 1990 a clinically useful
      anticonvulsant therapy for treatment-resistant epilepsy. Open acute and longer
      term data suggest the potential clinical utility of VNS as an antidepressant
      therapy especially in treatment refractory depression. The vagus nerve has
      connections to the limbic system and other brain structures which modulate
      affect. PET studies showed functional changes under VNS in such critical areas,
      which can explain the mechanisms of action of VMS. Ongoing studies will have to
      better establish its acute and longer-term efficacy, and specific indications in
      the treatment of depression.

PMID- 12048620
TI  - [The epilepsypsychoses].
AB  - The association of epilepsy, the epilepsypsychoses and schizophrenia has
      attracted the attention of psychiatrists and neurologists since the nineteenth
      century. While until the 1970ies German speaking psychiatry had shown great
      interest, in recent years there have been only a small number of publications on
      this topic. However there has been intensive research likewise on the
      epilepsypsychoses, especially on the association of temporal lobe epilepsy and
      schizophrenia in the English-speaking psychiatry. The epilepsypsychoses are
      inadequately categorized by the modern classification systems. Current knowledge
      of either the epilepsypsychoses or the relationship between epilepsy and
      schizophrenia is examined.

PMID- 12048621
TI  - [Delusional misidentifications. Symptoms and neuropsychological models].
AB  - Delusional misidentifications include the Capgras delusion, Fregoli delusion, the
      delusion of subjective doubles and other less frequent symptoms. A common
      denominator of these unspecific psychopathological symptoms is the patients'
      denial of their identity or the convinction that their identity or the identity
      of relatives has been altered. These delusional symptoms occur in the context of
      somatic and mental diseases, most frequently in schizophrenia and dementia.
      According to neuropsychological and neuroanatomical studies delusional
      misidentifications are facilitated by lesions of the temporo-limbic system
      leading to an impairment in the affective recognition and reality control.
      Patients suffering from delusional misidentifications have a higher risk of
      aggressive behaviour which emphasises their clinical relevance.

PMID- 12048622
TI  - [Borderline personality disorder and attentional biases. Theoretical models and
      empirical findings].
AB  - The purpose of this review is to analyse nature, degree and consequences of
      attentional biases in patients with borderline personality disorder based on
      existing literature. The clinical importance of these phenomena in patients with
      borderline personality disorder is strengthened and the link between theoretical
      models, empirical findings and therapeutic interventions is elaborated. This link
      between selective attention and borderline personality disorder is demonstrated
      on the basis of studies, which indicate a context between borderline pathology,
      affective disorders, anxiety disorders, and attention-deficit/hyperactivity
      disorders and also give evidence to neuropsychological deficits in patients with
      borderline personality disorder. The present article comparatively describes
      three theoretical models of borderline personality disorder and their possible
      links to attentional biases. The dialectical behavior approach postulates a
      pronounced attentional narrowing to emotional stimuli in connection with deficits
      regarding affect regulation. The cognitive approach assumes that rigid
      dysfunctional schemata initiate a cognitive-emotional circuit, which leads to a
      reinforcement of the symptomatology as a result of a biased perception and
      memory. Additionally the present article specifies the trauma approach which
      emphasizes the relation between borderline pathology and childhood trauma with
      recourse to theories of attentional biases in patients with traumatic
      experiences. Preliminary empiricial findings suggest that patients with
      borderline personality disorder demonstrate a general attentional bias for any
      emotional negative stimuli and not a selective attentional bias to borderline
      specific stimuli. Further studies should clarify, whether therapeutical
      interventions with the aim to influence attentional processes represent a useful
      complement to established therapies in patients with borderline personality
      disorder.

PMID- 12048623
TI  - Patient pain during colonoscopy: an analysis using real-time magnetic endoscope
      imaging.
AB  - BACKGROUND AND STUDY AIMS: Colonoscopy is generally perceived as being a painful
      procedure. Contributory factors are: stretching of the colonic wall and
      mesenteric attachments from looping of the instrument shaft, overinsufflation,
      the degree of torque or force applied to the colonoscope shaft, and patient pain
      threshold. The aim of this study was to determine the frequency of pain episodes
      experienced during diagnostic colonoscopy and the corresponding colonoscope
      configuration, utilizing real-time magnetic endoscope imaging (MEI). PATIENTS AND
      METHODS: Consecutive outpatients undergoing colonoscopy were studied. Patients
      with previous colonic resections were excluded. Procedures were commenced with
      antispasmodics only, and patient sedation was self-administered whenever
      significant discomfort was experienced, using a patient-controlled analgesia
      (PCA) syringe pump. All "demands" were correlated with the MEI record, which was
      subsequently analysed. RESULTS: A total of 650 demands were recorded in 102
      patients. Seventy-seven percent of all demands occurred with the colonoscope tip
      in the sigmoid colon, 7 % in the descending colon, 6 % at the splenic flexure, 5
      % in the transverse colon, and 4 % in the proximal colon. Ninety percent of all
      pain episodes coincided with either looping (79 %) or straightening of the
      colonoscope shaft (11 %); presumed overinsufflation being an infrequent cause of
      pain (9 %). Of the loops encountered during colonoscopy, the N-sigmoid spiral
      loop was associated with the majority of pain episodes (56 %). Looping was both
      more frequent ( P = 0.0002) and less well tolerated in women than in men ( P =
      0.0140). CONCLUSIONS: This study is the first to document pain at colonoscopy
      accurately. Looping, particularly in the variable anatomy of the sigmoid colon,
      is the major cause of pain, especially in women. Use of MEI may improve pain
      control by facilitating the straightening of loops within the sigmoid colon, and
      by enabling the endoscopist to target patient analgesia.

PMID- 12048624
TI  - Computed tomographic colonography (virtual colonoscopy): blinded prospective
      comparison with conventional colonoscopy for the detection of colorectal
      neoplasia.
AB  - BACKGROUND AND STUDY AIMS: Computed tomographic colonography (CTC), also known as
      virtual colonoscopy, is a recently introduced imaging modality for the detection
      of colorectal neoplasia. The aim of our study was to evaluate the performance of
      CTC in a blinded comparison with conventional colonoscopy. PATIENTS AND METHODS:
      A total of 66 consecutive, symptomatic patients underwent spiral computed
      tomography (CT) examination after standard bowel preparation. CT images were
      analyzed and subsequently compared with conventional colonoscopy findings.
      RESULTS: Conventional colonoscopy detected 15 colorectal carcinomas and 52
      polyps. CTC correctly identified all carcinomas, 13 of 14 polyps greater than
      10.0 mm (sensitivity 92.8 %; 95 % confidence interval (95 % CI); 77 - 100), 11 of
      13 polyps between 6.0 and 9.0 mm (sensitivity 84.6 %; 95 % CI; 62 - 100), and six
      of 25 polyps smaller than 5.0 mm (sensitivity 24 %; 95 % CI; 6 - 42). The per
      patient sensitivity and specificity were 93.7 % and 94.1 %, respectively.
      CONCLUSIONS: Computed tomographic colonography is an accurate imaging modality
      for the detection of colorectal neoplasia, especially for lesions larger than 6.0
      mm in diameter.

PMID- 12048625
TI  - Clinical impact of endoscopic ultrasonography at a county hospital.
AB  - BACKGROUND AND STUDY AIMS: Although endoscopic ultrasonography (EUS) is a well
      described examination method, there have been few reports concerning its clinical
      impact. The aim of this study was to describe EUS as it is performed at a county
      hospital, with an emphasis on the indications and clinical outcome. PATIENTS AND
      METHODS: Patients examined using EUS between December 1997 and November 2000 were
      recorded prospectively. Follow-up was conducted by examining each patient's
      medical records at least 3 months after the investigation. The EUS findings were
      compared with the patient's final diagnosis, and the decisions made by the
      referring department on the basis of each investigation were recorded. RESULTS: A
      total of 344 EUS procedures were performed. In the third year, the distribution
      of patients relative to the various referral diagnoses was: 78 with suspected
      benign pancreaticobiliary disease, 33 for staging of known upper gastrointestinal
      tract malignancy, 15 with suspected mediastinal disease or for staging of lung
      cancer, 13 with suspected submucosal lesions, and five with unclassified disease.
      Follow-up was possible in 340 patients (99 %). Compared to the final diagnosis in
      each patient, the sensitivity, specificity, and accuracy rates of EUS were 86 %,
      90 %, and 88 %, respectively. The EUS findings made more invasive procedures
      unnecessary in 199 patients (58 %). EUS led to a switch to less invasive
      procedures in 61 patients (18 %), and it had no influence on the further
      management strategy in 80 patients (24 %). CONCLUSIONS: EUS has a high level of
      accuracy and a substantial clinical impact when performed in an unselected
      population. The estimated numbers of investigations needed appear to justify
      setting up an EUS center at institutions with a catchment population of 350 000
      inhabitants.

PMID- 12048626
TI  - Scientific publications in endoscopic ultrasonography: a 20-year global survey of
      the literature.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasound imaging of mediastinum,
      gastrointestinal tract and pancreas, and endoscopic ultrasound-guided fine-needle
      aspiration of suspicious lesions, have now been available for several years.
      Although many papers have been published on endoscopic ultrasonography, a
      comprehensive overview of the subject matter presented has not yet been carried
      out. An extensive survey of the literature on endoscopic ultrasonography since
      its inception in the 1980 s was conducted in this study; key points are
      summarized. METHODS: A computer-based PubMed search system was used to retrieve
      all available abstracts pertaining to endoscopic ultrasound from 1980 to the
      present. Data were collected concerning the impact factor, the various EUS
      instruments and fine-needle aspiration biopsy techniques used, and the subject
      matter, as well as the journals publishing the abstracts. RESULTS: A total of
      1259 articles were published in 65 journals: 440 (35 %) Western European studies,
      404 (32 %) American studies, and 321 (26 %) Japanese studies were retrieved. The
      total and average impact factor per paper was highest for American papers,
      followed by European papers and Japanese papers. Forty-seven percent of the
      papers were published in Gastrointestinal Endoscopy and Endoscopy. The most
      frequently discussed topics concerned the staging of various malignancies,
      including esophageal, gastric, pancreatic, and colorectal cancer. The average
      sample size per paper was in the range 25 - 50. The various types of study
      included retrospective inquiries (25 %), reviews (24 %), prospective studies (17
      %), and case reports (15 %). CONCLUSIONS: Over the course of the past 20 years,
      there has been a progressive increase in the number of publications pertaining to
      endoscopic ultrasonography. Large-scale prospective studies are now needed to
      validate earlier reports. In addition, the diagnostic and therapeutic role of
      endoscopic ultrasound needs to be more widely publicized among physicians in all
      health-care fields, so that appropriate patients may be referred.

PMID- 12048628
TI  - Length of esophageal cancer and degree of luminal stenosis during upper endoscopy
      predict T stage by endoscopic ultrasound.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) is considered to be
      the most accurate modality for T staging of esophageal cancer. This study
      attempted to determine whether endoscopic features such as the length and degree
      of luminal stenosis in esophageal cancer can predict the T stage on EUS. PATIENTS
      AND METHODS: Thirty-five patients with newly diagnosed esophageal adenocarcinoma
      or squamous-cell carcinoma undergoing EUS prior to initiation of any treatment
      were included in the study. The length of the tumor was assessed prospectively
      during esophagogastroduodenoscopy (EGD) before EUS in 22 patients. Radial EUS was
      then performed in these patients. The other 13 patients had sufficient luminal
      stenosis to prevent complete advancement of the echo endoscope through the tumor.
      In these 13 patients, the length of the esophageal cancer was not examined, but
      the T and N stage up to the level of maximum advancement of the echo endoscope
      through the tumor were noted. RESULTS: All 13 patients with luminal stenosis had
      at least a T3 (n = 12) or T4 (n = 1) lesion up to the level of maximum
      advancement of the echo endoscope. Among the 22 patients in whom the length of
      the esophageal cancer was measured, the mean length in the 13 patients with a T1
      or T2 lesion on EUS was 2.6 cm. The mean length in the nine patients with T3
      esophageal cancer was 7.1 cm. The difference in the mean length of T1 or T2
      lesions (2.6 cm) was significantly different ( P < 0.001) from the mean length of
      T3 lesions (7.1 cm). Using a clinical diagnostic testing approach, when > or = 5
      cm length was used as a criteria for diagnosing T3 lesions, the sensitivity was
      89 %, specificity 92 %, positive predictive value 89 %, and negative predictive
      value 92 %. There was also a suggestion of increased chances of lymph-node
      metastases with increasing length of esophageal cancer. CONCLUSIONS: In
      esophageal carcinoma, endoscopic features such as the length of the cancer and
      the degree of luminal stenosis correlate with T staging on EUS. Esophageal
      cancers that are > or = 5 cm in length, or are sufficiently stenotic to prevent
      passage of an endoscope, are much more likely to be T3 or higher-stage lesions,
      while those that are < 5 cm in length have a greater chance (92 %) of being T1 or
      T2.

PMID- 12048627
TI  - Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and
      limitations for evaluating esophagopharyngeal invasion.
AB  - BACKGROUND AND STUDY AIMS: Although computed tomography (CT) and magnetic
      resonance imaging (MRI) are useful for detecting esophagopharyngeal invasion by
      thyroid cancer, they cannot assess the depth of invasion, which is important for
      the surgical planning. In the present study, endoscopic ultrasonography (EUS) of
      the esophagus was used to assess esophagopharyngeal invasion by thyroid cancer,
      and the value of this technique was assessed prospectively. PATIENTS AND METHODS:
      Between 1 December 1998 and 31 December 2000, EUS examinations were carried out
      in 59 patients in whom esophagopharyngeal invasion by thyroid cancer was
      suspected due to large tumors or tumors with poor mobility. The EUS findings were
      evaluated in 52 patients (10 men, 42 women; mean age 62.4 years; mean tumor size
      39.5mm) with complete resections, and compared with the pathological results.
      RESULTS: The diagnostic specificity and accuracy of EUS in assessing invasion
      into the muscularis propria (82.9 %, 82.7 %) were greater than those of MRI (60
      %; P = 0.034, 65.4 %; P = 0.044) and esophagography (58.8 %; P = 0.034, 60 %; P =
      0.028). The accuracy for detecting cancer invasion located in the upper part of
      the lobe was less than for invasion in the middle and/or lower parts of the lobe
      ( P = 0.020). Conclusions. EUS is useful for assessing esophagopharyngeal
      invasion by thyroid cancer, although its effectiveness may be limited in thyroid
      lesions located in the upper part of the lobe.

PMID- 12048629
TI  - Preoperative laparoscopic examination using surgical manipulation and
      ultrasonography for pancreatic lesions.
AB  - BACKGROUND AND STUDY AIMS: Unnecessary laparotomies in patients with advanced
      pancreatic disease are unlikely to provide any benefits and may compromise both
      the quality and duration of survival. The purpose of this study was to determine
      the contribution of laparoscopy and laparoscopic ultrasound to the diagnosis or
      staging, or both, of pancreatic lesions. PATIENTS AND METHODS: Fifty-two patients
      were diagnosed preoperatively with pancreatic cancer. The diagnoses made by
      laparoscopic ultrasonography (LUS) were compared with those made prior to the
      operation. Laparoscopic visualization of the body of the pancreas was obtained
      via an infragastric approach. For the laparoscopic examination of the head of the
      pancreas, a retroduodenal approach was used. RESULTS: In 52 patients with cancer
      of the pancreatic head and body, unresectable findings were observed in 13
      patients. Portal vein displacement without other unresectable findings was
      evident in six patients using LUS, and was confirmed at exploratory laparotomy in
      five patients. The surgical approaches were changed, with seven patients
      undergoing an open exploration for biliary drainage and the other six patients
      receiving endoscopic endoprostheses. In six of the 52 patients, LUS-guided needle
      biopsies and frozen-section examinations detected chronic pancreatitis (n = 4), a
      malignant lymphoma (n = 1), and an abdominal tuberculosis (n = 1), which were
      diagnosed preoperatively as pancreatic cancers and cysts. Only one patient
      undergoing the laparoscopic procedure had acute pancreatitis; this patient was
      treated conservatively. CONCLUSIONS: LUS, when combined with laparoscopic
      manipulations, may overcome many of the limitations of laparoscopy alone in the
      investigation of pancreatic lesions by providing an accurate diagnosis and
      assessment of the size and extent of the local dissemination.

PMID- 12048630
TI  - Endoscopic surveillance for gastric remnant cancer after early cancer surgery.
AB  - BACKGROUND AND STUDY AIMS: The aims of this article were to clarify the incidence
      of gastric remnant cancer after surgery for early gastric cancer, and to develop
      surveillance programs for patients who have undergone partial gastrectomy in
      order to detect such lesions at an early stage. PATIENTS AND METHODS: A total of
      642 patients with partial gastrectomy for early gastric cancer were enrolled in a
      surveillance program for gastric remnant cancer between 1985 and 1996. In 509
      patients, the interval between endoscopic examinations was no more than 2 years.
      RESULTS: Among the 509 patients examined periodically, 15 patients were diagnosed
      as having gastric remnant cancer; in 12 patients, the cancers were detected at an
      early stage. All gastric remnant cancers were found distant from the site of the
      anastomosis, and in eight patients the cancers were located on the lesser
      curvature. The cumulative 5-year prevalence rate was estimated as 2.4 % and the
      10-year prevalence rate as 6.1 %. The initial tumors in the patients with gastric
      remnant cancer were of the microscopically intestinal type, without exception.
      The interval between the preceding examination and diagnosis was shorter in the
      patients with early cancer than in those with advanced cancer ( P < 0.01).
      CONCLUSIONS: Periodical surveillance endoscopy for gastric remnant cancer is
      recommended after surgery for early gastric cancer, particularly in patients
      whose cancers are of the intestinal type. The examinations can be repeated at 2 -
      3-year intervals, and special attention should be given to the lesser curvature
      away from the anastomotic site.

PMID- 12048631
TI  - Evaluation of endoscopic hemostasis in upper gastrointestinal bleeding related to
      Mallory-Weiss syndrome.
AB  - BACKGROUND AND STUDY AIMS: The endoscopic hemostatic method has been introduced
      as a safe and effective mechanical approach to hemostasis for upper
      gastrointestinal bleeding related to Mallory-Weiss syndrome (MWS). However, the
      indications for when to use endoscopic treatment are debatable because many
      patients need only medical observation. The study was designed to evaluate the
      necessity and efficacy of endoscopic hemostasis in upper gastrointestinal
      bleeding related to MWS. PATIENTS AND METHODS: From July 1994 to May 2000, we
      conducted a clinical trial in 76 patients who were found by endoscopy to have
      active bleeding (I, spurting; II, oozing), protruding visible vessels (III),
      and/or adherent clots (IV). Two study periods can be differentiated: in the first
      3 years endoscopic treatment (n = 30) was prospectively analyzed and in the final
      3 years medical treatment (n = 46) was analyzed in both cases to compare the
      outcome in MWS bleeding II-IV. In the first study period, in addition, endoscopic
      treatment was randomised to an injection method, using a mixture of hypertonic
      saline and epinephrine (HSE) (n = 14) and a hemoclipping or band ligation method
      (n = 16). RESULTS: Rebleeding was observed in four of 14 patients who had
      received endoscopic hemostasis with HSE injection and one of 46 patients who had
      been managed with medical treatment. No rebleeding was found following
      hemoclipping or band ligation. While all rebleeding was in bleeding stigmata of
      the I (1) and II (4) grades, there was no rebleeding in protruding visible
      vessels (III) or in adherent clots (IV), regardless of treatment methods.
      CONCLUSIONS: Our results suggested that endoscopic hemostasis is not necessary in
      patients without active bleeding stigmata, and the mechanical hemostatic method
      is more effective than HSE injection in patients with active bleeding stigmata.

PMID- 12048632
TI  - Mechanism of the development of gastric ulcer after percutaneous endoscopic
      gastrostomy.
AB  - BACKGROUND AND STUDY AIMS: The present study was carried out in order to
      elucidate the mechanism of the development of gastric ulcer, one of the serious
      complications of PEG tube placement. PATIENTS AND METHODS: This retrospective
      study included 92 patients who underwent gastric endoscopy after PEG tube
      placement. Gastric ulcers detected at gastroscopy were examined in relation to
      the length of the protrusion from the PEG tubes intragastric bumper and the use
      of histamine H 2 -receptor antagonists. RESULTS: Gastric ulcers were found in
      nine of the 92 patients, and in all nine the ulcer was found on the posterior
      wall of the gastric body, where the tip of the PEG tube was attached. Seven of
      the 21 patients (33.3 %) who had a PEG tube with a long protrusion from the
      intragastric bumper developed gastric ulcer. By contrast, only two of the 71
      patients (2.8 %) who had a PEG tube with a short protrusion developed gastric
      ulcer. The use of H 2 -blockers had no significant impact on the development of
      gastric ulcer. CONCLUSIONS: The occurrence of gastric ulcer after PEG placement
      was attributable to the shape of the PEG tube within the intragastric space, and
      not to the use of H 2 -blockers, suggesting that appropriate placement of the PEG
      tube is an important factor in preventing gastric ulcer.

PMID- 12048633
TI  - Bedside scoring system to predict the risk of developing pancreatitis following
      ERCP.
AB  - BACKGROUND AND STUDY AIMS: Pancreatitis is the most common significant
      complication of endoscopic retrograde cholangiopancreatography (ERCP). The aim of
      the present study was to develop a simple scoring system that clinicians can use
      to predict the risk of post-ERCP pancreatitis. PATIENTS AND METHODS: We analyzed
      a prospectively assembled database of 1835 ERCP procedures at a single referral
      hospital. Multivariate logistic regression analysis was performed to identify
      risk factors for pancreatitis and determine their relative contributions. From
      these results, a scoring system was constructed. The performance of the scoring
      system was assessed on the entire procedure database and in selected subgroups.
      RESULTS: Multivariate analysis yielded four risk factors: pain during the
      procedure, cannulation of the pancreatic duct (PD), previous post-ERCP
      pancreatitis, and number of cannulation attempts. Based on the regression model,
      the scoring system was: 4 points for pain, 3 points for PD cannulation, 2 points
      for a history of post-ERCP pancreatitis, and 1 - 4 points depending on the number
      of cannulation attempts. A total score of 1 - 4 points was associated with a low
      risk of pancreatitis (< 2 %), while a score of 5 - 8 points had an intermediate
      risk (7 %), and a score of 9 or above had a high risk (28 %). CONCLUSIONS: This
      simple scoring system may enable clinicians to stratify patients into low-risk,
      medium-risk, and high-risk groups for the development of post-ERCP pancreatitis.
      In addition, when patients with suspected sphincter of Oddi dysfunction and
      patients who underwent minor papilla cannulation were analyzed separately, the
      scoring system was able to predict accurately the pancreatitis risk of these
      patients as well.

PMID- 12048634
TI  - The best way to painless colonoscopy.

PMID- 12048635
TI  - EUS and disease management.

PMID- 12048636
TI  - Minilaparoscopy-guided spleen biopsy in systemic disease with splenomegaly of
      unknown origin.
AB  - With the advent of a minimally invasive laparoscopy technique, the advantages of
      diagnostic laparoscopy are being rediscovered. We report here on four patients
      with systemic disease of unknown origin and splenomegaly, in whom minilaparoscopy
      guided splenic biopsy yielded a definitive diagnosis. Four patients with unclear
      systemic disease were studied using diagnostic minilaparoscopy and guided spleen
      biopsy, after failure of diagnostic work-up. Minilaparoscopic spleen biopsy
      revealed the diagnosis of a B-cell non-Hodgkin's lymphoma in two cases. In one
      patient, who had a history of Still's disease, the spleen biopsy showed
      granulocytic infiltration in the spleen typical of an acute episode of Still's
      disease. One patient with a known immunodeficiency syndrome (stage C III) showed
      multiple hypodense lesions in the spleen. Biopsy allowed a diagnosis of
      mycobacterial infection, with identification of Mycobacterium tuberculosis. No
      major complications occurred in any of the four cases; post-biopsy bleeding was
      observed in three of the four, but was easily managed by argon plasma coagulation
      or application of fibrin glue, or both. We recommend the use of spleen biopsy as
      a diagnostic tool in splenopathy of unknown origin if previous diagnostic methods
      have failed to yield a definitive diagnosis.

PMID- 12048637
TI  - A case of hyperplastic polyposis of the colon with adenocarcinomas in
      hyperplastic polyps after long-term follow-up.
AB  - A 66-year-old woman had been receiving follow-up since 1990 for hyperplastic
      polyposis, which remained unchanged endoscopically and radiologically. In 1999, a
      small (28 x 22 mm) superficial adenocarcinoma was detected in the ascending
      colon. Histologically, this was a hyperplastic polyp containing a well
      differentiated adenocarcinoma invading into the submucosa. A review of the
      English and Japanese literature identified 32 cases of "hyperplastic polyposis."
      In about half of the 32 cases, an adenocarcinoma was also found amongst the
      hyperplastic polyps. Half of the adenocarcinomas were located in the right colon.
      Although hyperplastic polyposis is uncommon, it warrants regular surveillance, as
      it appears to be associated with an increased risk of colorectal cancer.

PMID- 12048640
TI  - Laparoscopic gastrostomy.

PMID- 12048638
TI  - Duodenal duplication cyst.

PMID- 12048642
TI  - Screening for sporadic colorectal cancer.

PMID- 12048645
TI  - Percutaneous antegrade sphincterotomy under endoscopic retrograde control: report
      of two cases.

PMID- 12048644
TI  - A case of drug-induced colitis complicating the administration of
      hydroxycarbamide.

PMID- 12048646
TI  - Symptomatic ulceration of an acid-producing oesophageal inlet patch colonized by
      helicobacter pylori.

PMID- 12048647
TI  - Endoscopic ultrasonography features of colonic muco-submucosal elongated polyp.

PMID- 12048649
TI  - Abrupt withdrawal from intrathecal baclofen: recognition and management of a
      potentially life-threatening syndrome.
AB  - OBJECTIVE: To suggest guidelines for the prevention, recognition, and management
      of a life-threatening syndrome (high fever, altered mental status, profound
      muscular rigidity that sometimes progressed to fatal rhabdomyolysis) in patients
      who experience the abrupt withdrawal of intrathecal baclofen (ITB) therapy.
      DESIGN: Retrospective literature and safety-file review. SETTING: Expert panel
      drawn from physiatry, neurology, and neurosurgery. PARTICIPANTS: Experienced
      users of ITB therapy in the pediatric and adult populations in the United States.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: We reviewed literature
      reports, MedWatch reports to the US Food and Drug Administration, and our own
      experiences. We critically analyzed patient management and drug therapy in the
      context of the pharmacology of baclofen and other antispastic agents. RESULTS: An
      abrupt reduction in gamma-aminobutyric acid(B) (GABA) agonist activity in the
      central nervous system can cause the ITB withdrawal syndrome, which is clinically
      and pathophysiologically distinct from autonomic dysreflexia, malignant
      hyperthermia, and neuroleptic-malignant syndrome. ITB withdrawal evolves over 1
      to 3 days, but may become fulminant if not recognized and treated early. The
      syndrome can be interrupted by the restoration of ITB therapy. However,
      supportive measures and high-dose benzodiazepine infusion may be life saving in
      the interval before ITB therapy is resumed. Dantrolene infusion may relieve
      muscle rigidity but does not reverse the other manifestations of GABAergic
      agonist withdrawal. CONCLUSIONS: Most episodes of severe ITB withdrawal were
      preventable. Patients at risk can be identified and educated prospectively and
      given medication for emergency use. Treatment with GABAergic agonist drugs may
      prevent potentially fatal sequelae.

PMID- 12048650
TI  - Rehabilitation outcome of elderly patients after a first stroke: effect of
      cognitive status at admission on the functional outcome.
AB  - OBJECTIVE: To assess whether, and to what extent, cognitive outcome relates to
      overall functional outcome among elderly stroke patients. DESIGN: Nonconcurrent
      prospective study. SETTING: Geriatric rehabilitation division at a large, urban,
      academic, freestanding hospital in Israel. PARTICIPANTS: Three hundred thirty-six
      patients aged 60 years and older admitted consecutively for rehabilitation after
      first acute stroke. Inclusion criteria were met by 315 patients, who were
      included in the final analysis. Average age was 75.3 years. The stroke was right
      sided in 44.1%. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The motor
      subscale of the FIM instrument assessed functional status. Absolute functional
      gain was determined by the FIM motor gain. Relative functional gain was
      calculated according to the Montebello Rehabilitation Factor Score. Cognitive
      status was assessed with the Mini-Mental State Examination (MMSE) and the FIM
      cognitive subscale. RESULTS: FIM scores increased significantly during
      rehabilitation, mainly due to improvement in motor functioning. A strong
      association was found between the cognitive scales (r=.853, P<.001). Better
      rehabilitation outcomes were observed in patients with higher admission cognitive
      status, adjusting for the effect of age, sex, onset to admission interval, length
      of stay, and severity of stroke (odds ratio = 2.0; 95% confidence interval, 1.5
      2.5). CONCLUSIONS: Impaired cognitive status at admission negatively affects the
      rehabilitation outcome of elderly stroke patients. The utility of routinely using
      a cognitive test for all patients before admission to rehabilitation, preferably
      the MMSE, is emphasized. The time, cost, and effort involved in performing such a
      test are negligible, and the potential benefits are considerable.

PMID- 12048648
TI  - A major susceptibility locus for specific language impairment is located on
      13q21.
AB  - Children who fail to develop language normally-in the absence of explanatory
      factors such as neurological disorders, hearing impairment, or lack of adequate
      opportunity-are clinically described as having specific language impairment
      (SLI). SLI has a prevalence of approximately 7% in children entering school and
      is associated with later difficulties in learning to read. Research indicates
      that genetic factors are important in the etiology of SLI. Studies have
      consistently demonstrated that SLI aggregates in families. Increased monozygotic
      versus dizygotic twin concordance rates indicate that heredity, not just shared
      environment, is the cause of the familial clustering. We have collected five
      pedigrees of Celtic ancestry that segregate SLI, and we have conducted genomewide
      categorical linkage analysis, using model-based LOD score techniques. Analysis
      was conducted under both dominant and recessive models by use of three phenotypic
      classifications: clinical diagnosis, language impairment (spoken language
      quotient <85) and reading discrepancy (nonverbal IQ minus non-word reading >15).
      Chromosome 13 yielded a maximum multipoint LOD score of 3.92 under the recessive
      reading discrepancy model. Simulation to correct for multiple models and multiple
      phenotypes indicated that the genomewide empirical P value is <.01. As an
      alternative measure, we also computed the posterior probability of linkage (PPL),
      obtaining a PPL of 53% in the same region. One other genomic region yielded
      suggestive results on chromosome 2 (multipoint LOD score 2.86, genomic P value
      <.06 under the recessive language impairment model). Our findings underscore the
      utility of traditional LOD-score-based methods in finding genes for complex
      diseases, specifically, SLI.

PMID- 12048651
TI  - Postacute stroke guideline compliance is associated with greater patient
      satisfaction.
AB  - OBJECTIVE: To determine if the structure of care or the process of stroke care,
      as measured by compliance with stroke guidelines published by the Agency for
      Healthcare Research and Quality (AHRQ), is associated with patient satisfaction.
      DESIGN: Prospective inception cohort study of new stroke admissions including
      postacute care with follow-up interviews at 6 months poststroke. SETTING: Eleven
      Veterans Affairs medical centers (VAMCs). PARTICIPANTS: A total of 288 new stroke
      patients admitted to VAMCs. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Compliance with AHRQ stroke guidelines and patient satisfaction with care using a
      stroke-specific instrument. RESULTS: Process of care was positively and
      significantly associated with greater patient satisfaction even after controlling
      for patient functional outcome. The most visible (to the patient) process of care
      dimensions correlated most highly with patient satisfaction. Sixty-four percent
      (73/115) of patients expressed some dissatisfaction with 1 or more survey items.
      CONCLUSIONS: "What we do" and "how we do it" while providing postacute care to
      stroke patients was associated with patient satisfaction. This linkage of process
      to outcome is an important validation of satisfaction as a significant patient
      outcome. This linkage is further evidence that compliance with AHRQ stroke
      guidelines may be a valid quality of care indicator.

PMID- 12048652
TI  - Risk of falling: predictors based on reduced strength in persons previously
      affected by polio.
AB  - OBJECTIVES: To examine the contributions of sensorimotor factors to postural
      control and falling in people with prior polio and to determine whether these
      contributions differ from those found in normal populations. DESIGN: Survey and
      case-control study. SETTING: A falls and balance laboratory in Australia.
      PARTICIPANTS: Forty persons with prior polio (age range, 28-71 y) and 38 age- and
      sex-matched control subjects. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Lower-limb muscle strength, sway, vision, lower-limb sensation,
      reaction time, foot-tapping speed, and falls. RESULTS: Compared with the control
      subjects, the prior polio subjects performed similarly in sensory tests but worse
      in tests that involved a motor component. Within the prior polio group, lower
      limb strength was strongly associated with postural sway on a compliant surface
      and explained more of the variance in sway than in control subjects. Prior polio
      subjects who fell multiple times had reduced lower-limb strength, slower reaction
      time, lower foot-tapping speed, and increased sway compared with those who fell
      less often. However, the rate of decline in lower-limb strength within the prior
      polio group did not exceed normal, age-related changes. CONCLUSIONS: This
      investigation of prior polio subjects provides an appropriate model for studying
      muscle weakness as a falls risk factor. Weakness was directly associated with
      falls, and had an indirect effect mediated through increased sway.

PMID- 12048653
TI  - Predicting follow-up living setting in patients with stroke.
AB  - OBJECTIVE: To examine living setting at 3- to 6-month follow-up for inpatients
      with functional impairments discharged from medical rehabilitation. DESIGN:
      Retrospective performed by using information from the Uniform Data System for
      Medical Rehabilitation (UDSMR) representing medical rehabilitation patients
      across the United States. SETTING: National survey data. PARTICIPANTS:
      Information submitted in 1997 and 1998 to the UDSMR by 167 facilities from 40
      states was examined. A total of 9587 patient records were included in the final
      sample. The mean age +/- standard deviation was 70.2+/-12.4 years. The sample
      included 51.6% women and was comprised of 77.5% non-Hispanic white patients, with
      an average length of stay of 22.3+/-4.6 days. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Living setting (home vs not at home) at 3- to 6-month follow-up.
      RESULTS: A discriminant function training model including 8 statistically
      significant variables correctly classified 85.1% of the patients (n=8149). The
      total FIM instrument score, patient age, function-related group, and marital
      status were found to be useful classification variables. Wilks lambda for the
      model was.924 (chi(2)=1031.49, P<.000). The area under the receiver operating
      characteristics curve was.85. CONCLUSION: The association among functional
      abilities, demographic characteristics, and follow-up living setting in patients
      with stroke is complex. Functional variables can be used to help predict follow
      up living setting. These variables change based on patient severity level.

PMID- 12048654
TI  - Goal attainment scaling in the rehabilitation of patients with lower-extremity
      amputations: a pilot study.
AB  - OBJECTIVE: To assess the interrater reliability, construct validity, and
      responsiveness of Goal Attainment Scaling (GAS) among patients who have had lower
      extremity amputations. DESIGN: Pilot study comparing GAS with 2 functional
      measures with established reliability, validity, and responsiveness values.
      SETTING: Regional amputee program in southwestern Ontario. PARTICIPANTS: Ten
      patients (6 women, 4 men; mean age +/- standard deviation, 72.3+/-10.7 y) with
      unilateral lower-extremity amputations who were consecutively admitted to a
      regional amputee program. The ratio of transtibial to transfemoral amputations
      was 6:4. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects were
      assessed by using GAS, the Barthel Index, and the Locomotor Capabilities Index
      (LCI) of the Prosthetic Profile of the Amputee. RESULTS: The interrater
      reliability of GAS was r=.67, and 63% of goals developed were identified
      independently by both investigators. The construct validity between GAS and the
      Barthel Index and the LCI was r=.44 and r=.35, respectively. GAS was more
      responsive than both the Barthel Index and the LCI, as indicated by the
      calculation of effect sizes and relative efficiencies. CONCLUSION: This pilot
      study suggests that GAS is a promising outcome measure for the rehabilitation of
      patients with lower-extremity amputations.

PMID- 12048655
TI  - Establishing a standardized clinical assessment tool of pathologic and prosthetic
      hand function: normative data, reliability, and validity.
AB  - OBJECTIVE: To develop a new assessment procedure, the Southampton Hand Assessment
      Procedure (SHAP), that allows contextual results of hand function to be obtained
      readily in a clinical environment. DESIGN: Reliability (test-retest, interrater)
      and validity (criterion, content) of new assessment procedure against standard
      medical outcome measure techniques. SETTING: Normative data collected in a
      university laboratory. PARTICIPANTS: Twenty-four volunteers selected on the basis
      of optimum hand function using these criteria: age (range, 18-25 y), and no
      adverse hand trauma, neurologic condition, or disabling effects of the upper
      limb. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The normative control
      group was assessed for variability, and the procedure measured in terms of
      interrater and test-retest reliability. The absence of a direct comparison
      prevents a criterion standard from being established; however, content validity
      was shown by expert peer review. RESULTS: The control group data were shown to be
      multivariate gaussian; test-retest and interrater reliability were demonstrated
      at the 95% confidence level. The content validity was demonstrated by peer panel
      approval. CONCLUSIONS: Results of the control group established the statistical
      integrity of SHAP. Clinical trials are underway, although more extensive use of
      the procedure is advocated in primary care and rehabilitation centers where
      physiotherapy and occupational therapy are actively used in hand rehabilitation.

PMID- 12048656
TI  - Effectiveness of serial casting in patients with severe cerebral spasticity: a
      comparison study.
AB  - OBJECTIVE: To compare the improvement and complication rate between a technique
      using a short casting interval and a more conventional changing interval. DESIGN:
      A retrospective case-comparison study. SETTING: A rehabilitation center for
      adults with neurologic disorders. PARTICIPANTS: One hundred five patients with
      cerebral spasticity of different etiologies treated with serial casting to
      relieve fixed contractures caused by increased muscle tone. INTERVENTION: Serial
      casting of 172 joints (42 elbow, 41 wrist, 21 knee, 68 ankle joints), with cast
      changing intervals of 5 to 7 days (group 1:92 joints, 56 patients), or 1 to 4
      days (group 2:80 joints, 49 patients). MAIN OUTCOME MEASURES: Percentage of
      normal maximum range of motion (ROM) at the completion of casting and 1 month
      after discontinuation, and the number of complications resulting from casting
      procedure. RESULTS: Improved percentage ROM immediately after serial casting and
      1 month later in both groups (F=1469.5, P<.001). No differences in ROM
      improvement between groups were observed (F=0.3, P=.72). Complications in serial
      casting were found in 19.8% of 172 casting procedures, in 29.3% in group 1 and in
      8.8% in group 2 (chi(2)=10.2, P=.001). Discontinuations of treatment because of
      casting complications or other reasons were observed in 12.8% of the entire
      sample, in 18.5% in group 1 and in 6.3% in group 2 (chi(2)=4.7 P=.03).
      CONCLUSION: Casting is effective in the treatment of fixed contractures of the
      upper and lower extremities caused by increased muscle tone of cerebral origin.
      Short changing intervals in serial casting provide improvements in ROM comparable
      with conventional changing intervals, and result in fewer complications.

PMID- 12048657
TI  - Employment outcomes of adults who sustained spinal cord injuries as children or
      adolescents.
AB  - OBJECTIVES: To determine employment outcomes of adults with pediatric-onset
      spinal cord injury (SCI) and factors associated with those outcomes. DESIGN:
      Structured interview, including standardized measures. SETTING: Community.
      PARTICIPANTS: Individuals who sustained an SCI at age 18 years or younger, were
      24 years or older at follow-up, did not have a significant brain injury, and were
      living in the United States or Canada. A total of 195 subjects were interviewed.
      Mean age at injury was 14 years (0-18 y), mean age at interview was 29 years (24
      37 y), and mean duration of injury was 15 years (7-28 y). All participants had
      been enrolled in SCI programs. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: A structured interview, the FIM instrument, the Craig Handicap
      Assessment and Recording Technique, the Medical Outcomes Study 12-Item Short-Form
      Health Survey, and the Satisfaction with Life Scale. RESULTS: Of the
      participants, 99 (51%) were employed, 78 (40%) were unemployed, 12 (6%) were
      students, and 6 (3%) were homemakers. A predictive model of employment identified
      4 factors associated with employment: education, community mobility, functional
      independence, and decreased medical complications. Other variables significantly
      associated with employment included community integration, independent driving,
      independent living, higher income, and life satisfaction. CONCLUSIONS: Compared
      with the general population, the high rate of unemployment among adults with
      pediatric-onset SCI is a cause for concern. Risk factors associated with adult
      unemployment provide guidelines for targeting rehabilitation resources and
      strategies.

PMID- 12048658
TI  - Adaptive sweat gland response after spinal cord injury.
AB  - OBJECTIVE: To compare the eccrine gland cholinergic sensitivity of upper (UE) and
      lower (LE) extremities in untrained able-bodied individuals (UAB), untrained
      individuals with spinal cord injury (U/SCI), and trained wheelchair athletes
      (E/SCI). DESIGN: Static group comparison. SETTING: SCI population. PARTICIPANTS:
      A total of 25 men (mean age, 27.8+/-5.0 y; mean height, 175.8+/-9.1cm; mean
      weight, 76.2+/-7.7 kg) were categorized into 3 groups UAB (n=10), U/SCI (n=10),
      and E/SCI (n=5). Individuals with SCI had injuries ranging from C4-8.
      INTERVENTIONS: Peripheral sweat production was induced by using pilocarpine
      iontophoresis at surface landmarks relative to the flexor carpi radialis and
      medial gastrocnemius muscles. MAIN OUTCOME MEASURES: Peripheral sweat rate (SR),
      sweat gland density (SGD), and sweat per gland (S/G) were calculated for both UE
      and LE. RESULTS: Peripheral SR for the UAB in both UE (7.58+/-1.99 g x m(-2) x
      min(-1)) and LE (4.42+/-1.23 g x m(-2) x min(-1)) were significantly greater than
      those for U/SCI (1.08+/-1.01 g x m(-2) x min(-1), .24+/-.35 g x m(-2) x min(-1),
      respectively) and E/SCI (3.61+/-2.1 g x m(-2) x min(-1),.71+/-.81 g x m(-2). min(
      1), respectively). Furthermore, the UE versus LE SR ratio was calculated at
      1.71:1 for UAB subjects, whereas U/SCI and E/SCI subjects showed a ratio of
      4.50:1 and 5.07:1, respectively. UE SGD measures in U/SCI (83.20+/-39.84
      glands/cm(2)) persons were significantly less than either the UAB (120.20+/-21.42
      glands/cm(2)) or the E/SCI (120.80+/-21.56 glands/cm(2)). CONCLUSIONS: These
      results may indicate that sweat glands below the lesion are less sensitive to
      cholinergic activation, regardless of central or exogenous stimulation. However,
      glands above the level of the lesion may exhibit increased productivity when
      individuals are exposed to physical training and physiologic stress.

PMID- 12048659
TI  - Functional magnetic stimulation facilitates gastric emptying.
AB  - OBJECTIVE: To evaluate the effect of functional magnetic stimulation (FMS) on
      gastric emptying in able-bodied and spinal cord injury (SCI) subjects. DESIGN: A
      prospective, nonrandomized clinical experiment. SETTING: SCI and disorder center
      in a Veterans Affairs medical facility. PARTICIPANTS: Five healthy, able-bodied
      subjects and 4 subjects with SCI. INTERVENTION: A commercially available magnetic
      stimulator was used; a round magnetic coil was placed along the T9 spinous
      process. The intensity of the magnetic stimulation was 60%, with a frequency of
      20 Hz, and a burst length of 2 seconds for the gastric emptying protocol. Man
      Outcome Measures: Rate of gastric emptying and time required to reach gastric
      emptying half-time (GE(t1/2)) with and without FMS. Data fit into linear
      regression curve. RESULTS: Accelerated gastric emptying was achieved in both able
      bodied and SCI subjects. The mean +/- standard error of mean of the GE(t1/2) at
      baseline and with FMS was 36+/-2.9 minutes and 33+/-3.1 minutes, respectively,
      for able-bodied subjects, and 84+/-11.1 minutes and 59+/-12.7 minutes,
      respectively, for SCI subjects. CONCLUSION: Gastric emptying was enhanced by FMS
      in able-bodied subjects and was greatly enhanced in SCI subjects. FMS can be a
      useful noninvasive therapeutic tool to facilitate gastric emptying in humans.

PMID- 12048660
TI  - Test-retest strength reliability: hand-held dynamometry in community-dwelling
      elderly fallers.
AB  - OBJECTIVE: To determine the reliability of a standardized protocol by using a
      hand-held dynamometer (HHD) to measure lower-extremity strength in community
      dwelling elderly fallers. DESIGN: Within-session test-retest reliability of the
      HHD. SETTING: Balance laboratory of a university. PARTICIPANTS: A convenience
      sample of 41 community-dwelling elders (61-90y) who fell at least once in the
      previous year. INTERVENTION: The strengths of 8 lower-extremity muscle groups
      bilaterally were tested twice, with an intervening rest period of 15 seconds.
      MAIN OUTCOME MEASURE: Maximal isometric force. RESULTS: Test-retest intraclass
      correlation coefficients (ICCs) were high, generally ranging from.95 to.99 for 1
      trial (ICC(2,1)) and from.97 to 1.00 for the mean of 2 trials (ICC(2,2)). There
      were no significant differences in strength values across trials (P>.05). Men had
      significantly greater strength than women across all muscle groups (P>.05). Right
      knee extensor strength demonstrated the largest trial-to-trial difference,.54 kg
      using a single measurement and.39 kg using the mean of both measurements. Among
      the 3 lower-extremity muscle groups, the ankle showed higher a coefficient of
      variation (CV=5.1%-7.4%) than the knee (CV=4.6%-5.1%) or the hip (CV=4.2%-6.3%)
      when using 1 measure. CONCLUSION: By using an HHD and a standardized measurement
      protocol, a novice tester can obtain reliable lower-extremity strength values in
      community-dwelling elderly fallers.

PMID- 12048661
TI  - Muscle activation patterns in subjects with and without low back pain.
AB  - OBJECTIVE: To analyze muscle activation patterns during various footplate
      perturbations, used as proprioceptive challenges in patients with low back pain
      (LBP) and in controls. DESIGN: A prospective and controlled comparative study.
      SETTING: Outpatient clinic. PARTICIPANTS: Twenty subjects with chronic LBP and 20
      age- and sex-matched controls. INTERVENTIONS: The subjects underwent 5 sets of
      footplate perturbations in 3 directions with 16 perturbations for each set. MAIN
      OUTCOME MEASURES: Latency, frequency, and asymmetry of muscle activation of the
      erector spinae, rectus abdominus, anterior tibialis, and gastrocnemius muscles
      were measured bilaterally with surface electromyography. RESULTS: In the toes-up
      movements, subjects with LBP were significantly less likely to activate their
      rectus abdominus muscles (P=.02), and they were more likely to exhibit asymmetric
      muscle activation in the smaller forward movements (odds ratio=4.1, P=.03). The
      latter result appears to be driven by asymmetric contraction of the erector
      spinae and rectus abdominus. CONCLUSIONS: Significantly more subjects with LBP
      than control subjects exhibited absent firing of trunk muscles during 2 of the 5
      footplate perturbations. These results suggest an abnormality of the
      neuromuscular loop and may represent altered proprioception.

PMID- 12048662
TI  - The use of Rasch measurement to improve the Oswestry classification scheme.
AB  - OBJECTIVES: To use Rasch measurement to assess and modify the original
      classification categories of the Oswestry Low Back Pain Disability Questionnaire
      (Oswestry), to examine the hypothesis that the items from the Oswestry form a
      unidimensional construct and a hierarchical representation of low back pain (LBP)
      disability, and to compare ordinal Likert resultant scores to interval Rasch
      scaled scores with disability categories serving as a framework. DESIGN: Rasch
      analysis model. Existing Oswestry admission data generated by FOTO were analyzed.
      SETTING: Statistical analysis of sample database. PARTICIPANTS: A sample of 942
      patients with LBP referred for physical therapy between 1993 and 1994.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Construct validity;
      disability categories (as assessed by Likert and Rasch models); and fit
      statistics (infit, outfit as mean squares). RESULTS: All items from the Oswestry
      except the pain item fit the Rasch model. Construct validity of the scale using
      the Rasch model required the structure of the rating scale to be modified from 6
      response levels to 4. A hierarchical representation of LBP disability was
      supported. A comparison of the disability categories based on Likert and Rasch
      scaling revealed them to be nonequivalent. The new scaling changed the disability
      categories for 44% of patients. CONCLUSION: Rasch analysis produced disability
      categories in the Oswestry that are linear and, therefore, useful for
      quantitatively assessing self-reported disability levels.

PMID- 12048663
TI  - Pulsed short-wave diathermy effects on human fibroblast proliferation.
AB  - OBJECTIVES: To investigate the influence of pulsed short-wave diathermy (PSWD) on
      fibroblast and chondrocyte cell proliferation rates and to establish the
      influences of different dosages applied. DESIGN: Four single-blind trials.
      SETTING: Laboratory, in vitro study. SPECIMENS: Human adult dermal fibroblast and
      chondrocyte cells were plated at known concentrations and incubated for 5 days.
      INTERVENTION: Exposure to PSWD, twice daily, on days 2, 3, and 4. MAIN OUTCOME
      MEASURE: After crystal violet staining (day 5), optical density (cell number) was
      determined spectrophotometrically. RESULTS: PSWD, given at mean power of 48W for
      10 minutes, increased fibroblast proliferation compared with control groups
      (P<.001). There was a relationship between cell proliferation and the amount of
      energy given (P<0.001). The optimal mean power for proliferation was estimated to
      be 13.8W. While keeping mean power constant at 6W, altering pulse duration and
      pulse repetition rate dosage parameters did not have a significant effect on
      proliferation (P=.519). Chondrocyte proliferation also increased with PSWD
      exposure of 6W at 10 minutes duration (P=.015). In addition, treatment time was
      significantly associated with chondrocyte proliferation (P<.001). CONCLUSION:
      PSWD is associated with increased rates of fibroblast and chondrocyte
      proliferation in vitro, which is dose dependent. These results contribute to an
      understanding of the physiologic mechanisms underlying the therapeutic effects of
      PSWD.

PMID- 12048665
TI  - Jamais vu episodes in relationship to baclofen treatment: a case report.
AB  - A 37-year-old man presented with new onset jamais vu episodes. Jamais vu is a
      mental state characterized by a sense of unfamiliarity in a familiar situation.
      The patient's episodes of jamais vu were unrelated to any known factor other than
      his use of baclofen. The episodes, which occurred as each baclofen dose wore off,
      resolved after the baclofen dose that triggered it was discontinued. The patient
      has had no recurrence of jamais vu states after discontinuation of his baclofen.
      This is the first known case report of jamais vu episodes caused by baclofen.
      Although jamais vu episodes can occur in healthy persons, they are known to occur
      more frequently in persons with epilepsy, fatigue, psychologic states, or
      intoxications. This case suggests that medications should be considered as a
      possible cause of jamais vu episodes.

PMID- 12048664
TI  - The use of federal and state databases to conduct health services research
      related to physical and occupational therapy.
AB  - OBJECTIVE: To describe the characteristics of a number of secondary databases
      that have the potential to answer questions related to the use of, access to, and
      effectiveness of physical therapy (PT) and occupational therapy (OT). DATA
      SOURCES: Federal and state databases maintained by the National Center for Health
      Statistics, the Agency for Healthcare Research and Quality, and the Centers for
      Medicare and Medicaid Services. STUDY SELECTION: Databases, described above, that
      were identified as having potential for answering questions related to the use
      and effectiveness of PT and OT were examined. DATA EXTRACTION: The databases were
      explored to determine if PT and OT had sufficient representation, and if so, to
      identify potential questions that could be answered by examining the databases in
      more detail. Some of the advantages, disadvantages, and methodologic issues of
      using the databases were identified. DATA SYNTHESIS: Several databases are
      available that can be used by researchers to increase our understanding of the
      use of, access to, and/or effectiveness of PT and OT. Many of the databases are
      most suited for examining issues related to the use of and access to these
      services. A few of the databases can be used to examine the effectiveness of PT
      and OT. CONCLUSION: Secondary data analyses are a particularly useful, cost
      effective, and efficient means for preliminary exploration of topics that are not
      well understood, such as the use of, access to, and effectiveness of PT and OT.

PMID- 12048666
TI  - Pedicled groin flaps for upper-extremity reconstruction in the elderly: a report
      of 4 cases.
AB  - The pedicled groin flap is a useful, versatile flap for coverage of wounds of the
      hand and distal forearm. It produces predictable results with a procedure that is
      much less difficult to perform and takes less time than a free-tissue transfer.
      Contrary to the general belief that the groin flap should not be used in the
      elderly because of the risk of shoulder stiffness, we found satisfactory results
      with this procedure in 4 elderly patients (age range, 59-75 y) when immediate
      shoulder mobilization was instituted and physical therapy was continued during
      flap maturation and pedicle division.

PMID- 12048667
TI  - Heterotopic ossification in critical illness and cancer: a report of 2 cases.
AB  - Heterotopic ossification is the abnormal development of bone tissue within
      periarticular soft tissue. We present 2 Turkish patients with malignant thoracic
      cancer who underwent extensive thoracic surgery and required prolonged
      postoperative chemical paralysis and cardiorespiratory support for respiratory
      complications. Both patients were found by the physiatrist to have multiple,
      extensive heterotopic ossifications. Clinical findings in both patients included
      joint swelling and severe limitation in range of motion (ROM) associated with
      pain. The diagnoses were confirmed radiographically. After an extended length of
      inpatient rehabilitation, both patients improved their cumulative FIM instrument
      motor scores by 23 and were discharged with a trained family member. Our findings
      suggested that heterotopic ossification should be suspected in patients
      presenting with decreased ROM, increased pain, and joint swelling after prolonged
      immobilization. Serum alkaline phosphatase might be used as an effective
      screening tool.

PMID- 12048668
TI  - Low back pain and myalgias in acute and relapsed mast cell leukemia: a case
      report.
AB  - Mast cell leukemia is a rare, severe disease that may manifest through an array
      of clinical presentations, including vasomotor flushing and hypotension. Leukemic
      infiltrate of muscle and bone may rarely occur, resulting in nonspecific
      myalgias, bony pain, and neuropathic pain secondary to compression of nerves by
      bone. Mast cell leukemia as a clinical entity has not been well described. We
      present the case of a 25-year-old man with a remote medical history of germ cell
      tumor who was initially diagnosed with mast cell leukemia after presenting with
      low back pain. One and a half years later, the patient presented with a chief
      complaint of back pain and myalgias and was found to have relapsed mast cell
      leukemia. Medical management and, specifically, rehabilitation of these patients
      can be extremely difficult. This report shows the complex management of patients
      with mast cell leukemia.

PMID- 12048669
TI  - Risks of falls in subjects with multiple sclerosis.
AB  - OBJECTIVES: To quantify fall risk among patients with multiple sclerosis (MS) and
      to report the importance of variables associated with falls. DESIGN:
      Retrospective case-control study design with a 2-group sample of convenience.
      SETTING: A hospital and home settings in Italy. PARTICIPANTS: A convenience
      sample of 50 people with MS divided into 2 groups according to their reports of
      falls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Subjects were
      assessed with questionnaires for cognitive ability and were measured on their
      ability to maintain balance, to walk, and to perform daily life activities. Data
      regarding patients' strength, spasticity, and transfer skills impairment were
      also collected. RESULTS: No statistical differences were found between groups of
      fallers and nonfallers using variables pertaining to years after onset, age,
      gender, and Mini-Mental State Examination. Near statistically significant
      differences were found in activities of daily living and transfer skills (P<.05).
      Three variables were associated with fall status: balance, ability to walk, and
      use of a cane (P<.01). Those variables were analyzed using a logistic regression.
      The model was able to predict fallers with a sensitivity of 90.9% and a
      specificity of 58.8%. CONCLUSIONS: Variables pertaining to balance skills, gait
      impairment, and use of a cane differed between fallers and nonfallers groups and
      the incidence of those variables can be used as a predictive model to quantify
      fall risk in patients suffering from MS. These findings emphasize the
      multifactorial nature of falls in this patient population. Assessment of
      different aspects of motor impairment and the accurate determination of factors
      contributing to falls are necessary for individual patient management and therapy
      and for the development of a prevention program for falls.

PMID- 12048671
TI  - Seat-interface pressures on various thicknesses of foam wheelchair cushions: a
      finite modeling approach.
AB  - OBJECTIVE: To investigate the effect of cushion thickness on subcutaneous
      pressures during seating by using a finite element modeling approach. DESIGN:
      Seat-interface pressure measurements were used in a computational model. SETTING:
      Biomechanics laboratory. PARTICIPANT: A single healthy man (weight, 70 kg).
      INTERVENTIONS: Subject sat upright either with or without cushions of various
      heights. Seat-interface pressures measured by using a sensor mat interfaced to a
      personal computer sampling at 15 Hz. MAIN OUTCOME MEASURES: Peak seat-interface
      pressure; finite-element software was used to model the buttock, ischial
      tuberosity, and seat cushion. Subcutaneous stresses were calculated from the
      model. RESULTS: The region of highest subcutaneous stress in the soft tissue was
      concentrated within 1 or 2 cm of the ischial tuberosity, with the maximum
      compressive stress inferior to the bottom surface of the ischial tuberosity. The
      maximum subcutaneous stress, maximum seat-interface pressure, and maximum
      subcutaneous shear stress each changed with cushion thickness. Subcutaneous
      pressures decreased with thicker cushions, but almost all of the reduction was
      obtained with an 8-cm cushion. The amount of subcutaneous shear stress increased
      slightly for thicker cushions. The maximum subcutaneous stress was greater than
      the maximum interface pressure but not by a constant factor. Instead, the former
      was consistently larger by 0.7 to 0.8 N/cm(2). CONCLUSIONS: Cushion use reduced
      the maximum subcutaneous stress inferior to the ischial tuberosity. However,
      increasing the cushion thickness beyond 8 cm was ineffective in further reducing
      subcutaneous stress. It was also found that seat-interface pressures were a good
      indicator of the subcutaneous stress reduction in seating.

PMID- 12048670
TI  - The effects of body mass index on peak seat-interface pressure of
      institutionalized elderly.
AB  - OBJECTIVE: To determine if body mass index (BMI) influenced seat-interface
      pressure in a population of institutionalized elderly. DESIGN: A cross-sectional
      comparison of peak seat-interface pressure in 4 groups of institutionalized
      elderly was compared with BMI scores defined as either thin (<20 kg/m(2)),
      desirable range (20-24.9 kg/m(2)), grade I obesity (25-29.9 kg/m(2)), or grade II
      obesity (30-40 kg/m(2)). SETTING: Several small nursing homes and a university in
      a small urban community. PARTICIPANTS: A convenience sample of 75 individuals
      (age range, 65-95 y) living in 1 of 3 skilled nursing facilities. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: The Novel Pliance seat pressure-mapping
      system was used to collect seat-interface pressure data. Each participant was
      asked to sit in the wheelchair for up to 10 minutes while the seat-interface
      pressures were recorded. Body weight and height of each participant were obtained
      from the medical chart; these characteristics were then used to calculate a BMI
      for each participant. RESULTS: A 1-way analysis of variance on the peak seat
      interface pressures revealed significant differences between the 4 groups
      (P<.05). Post hoc comparisons showed differences in peak seat-interface pressure
      between the thin and desirable range groups (P<.05), the thin and grade I obesity
      group (P<.05), and the thin and grade II obesity groups (P<.05). Differences in
      peak seat-interface pressure decreased as BMI increased. CONCLUSIONS: The results
      are consistent with the results of a previous study of individuals with spinal
      cord injuries. In the current study, peak seat-interface pressure was highest in
      the thin elderly group, which had the lowest BMI levels of any of the 4 groups.
      Differences in the peak seat-interface pressures were less as BMI increased.

PMID- 12048672
TI  - Effect of foot orthoses on 3-dimensional kinematics of flatfoot: a cadaveric
      study.
AB  - OBJECTIVE: To test in cadaveric feet the hypothesis that prefabricated foot
      orthoses will improve arch alignment in flatfoot deformity. DESIGN: Experimental,
      paired comparisons. SETTING: Biomechanics laboratory. CADAVERS: Nine cadaveric
      lower-extremity specimens with no abnormalities. INTERVENTIONS: To evaluate the
      performance of 2 orthoses specimens were tested in 4 combinations: intact,
      flatfoot, flatfoot with shoe and orthosis 1, and flatfoot with shoe and orthosis
      2. To simulate the midstance phase of gait, loads were applied to 5 tendons and
      an axial load equivalent to two thirds of the standing load was applied to the
      foot's plantar surface. MAIN OUTCOME MEASURES: Arch height and tarsal bone
      positions before and after a flatfoot deformity created by ligament sectioning;
      tarsal bone positions determined with a magnetic tracking system. RESULTS: After
      ligament sectioning, the average decrease in arch height with a shoe applied was
      4.6+/-1.6mm (8%); with orthosis 1, mean arch height increased 0.7+/-0.6mm
      (P=.008); with orthosis 2, it increased 0.3+/-0.5mm (P=.05). With both orthoses,
      arch height after sectioning was significantly less than that of the normal arch.
      Compared with the flatfoot condition, metatarsal-talar alignment improved in
      plantar flexion and inversion with both orthoses but did not approximate normal
      with either orthosis. Calcaneal-tibial position did not improve with either
      orthosis and was markedly different from that in the intact foot with either
      orthosis. No difference was found between the 2 orthoses except for metatarsal
      talar motion in external rotation (P=.014) and eversion (P=.026). CONCLUSIONS:
      Arch alignment improved significantly but to a limited degree (<2%) in cadaveric
      feet with the use of orthoses. Hindfoot valgus malalignment did not consistently
      improve by the use of shoe inserts.

PMID- 12048673
TI  - [Case-control study and transmission/disequilibrium test of childhood absence
      epilepsy].
AB  - OBJECTIVE: To investigate whether or not the gamma-aminobutyric acid (GABA)
      receptor subtype A genes GABRA5 and GABRB3 are associated with childhood absence
      epilepsy (CAE). METHODS: Two microsatellite DNA, GABRA5 and GABRB3, adjoining to
      chromosome 15q11.2-q12 were used as genetic markers. Both case-control study and
      transmission/disequilibrium test (TDT) as well as fluorescence-based semi
      automated genotyping technique were used in 90 trios with CAE and 100 controls to
      conduct association analysis. RESULTS: The allele frequencies of the 2
      microsatellite DNA in Chinese normal population are in good agreement with Hardy
      Weinberg equilibrium. The polymorphism information content of microsatellite DNA
      GABRA5 and GABRB3, are 0.80 and 0.66 respectively. The allele 2 frequency of
      microsatellite DNA GABRA5 and the allele 5 frequency of microsatellite DNA GABRB3
      are significantly higher in CAE patients than those in normal controls(P<0.001).
      CONCLUSION: Both microsatellite DNA GABRA5 and GABRB3 are good genetic markers.
      The gamma-aminobutyric acid receptor subtype A genes GABRA5 and GABRB3 may be
      directly involved either in the etiology of CAE or in linkage disequilibrium with
      disease-predisposing sites.

PMID- 12048674
TI  - [The relationship between physical distance and genetic distance on chromosome
      22].
AB  - OBJECTIVE: To construct a genetic map based on data from the Chinese population
      in northern part of China and to compare relationship between physical distance
      and genetic distance on chromosome 22. METHODS: PCR amplification was employed to
      genotype 6 STR loci on chromosome 22, and pedigree analysis was performed.
      RESULTS: A genetic map of Chinese Han population in the northern part of China
      was constructed and a preliminary comparison of the physical and genetic
      distances between 6 STR loci on chromosome 22 was made. CONCLUSION: There is
      complex relationship between genetic distance and physical distance: the distance
      between STR loci is related to physical distance but also recombination fraction,
      and there are differences of the genetic and physical distances on chromosome 22
      between Chinese and Caucasian, and between the male and female.

PMID- 12048675
TI  - [Inhibitory effect of all-trans-retinoid and polyphenon-100 on microsatellite
      instability in a colon cancer line].
AB  - OBJECTIVE: To investigate the effects of all-trans-retinoic acid(ATRA) and
      polyphenon-100 (PP) on genetic instability of human tumor cells via their role in
      alteration of microsatellite sequence(MS) and the expression of mismatch repair
      gene hMLH(1) and hMSH(2) in RER(+) (replication error) cells. METHODS: RER(+)
      colon cancer cell line was used as a host for lipofection with pCMV-CAR in which
      a foreign (CA)(14) repeat was inserted in the coding sequence of LacZ reporter
      gene, resulting in misreading LacZ frame. Any mutation which made the base number
      of (CA)(14) tract to be 3-fold resumed normal reading frame of LacZ, and thus led
      to expression of beta-galactosidase. Variable expression of LacZ in the
      transfectant cells resulting from RATA or PP treatment was measured by OD reading
      at lambda 620 after X-gal staining. Expression of mismatch repair genes of
      hMLH(1) and hMSH(2) was examined at mRNA level by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: ATRA at 1 mu mol/L, 0.1 u mol/L and
      PP at 3 mu g/ml had no significant inhibitory effect on cell proliferation. After
      being treated with ATRA or PP for 1 week, the blue cells of RKO transfectant
      clones were significantly reduced, and this meant the mutation of exogenous
      (CA)(14) in RKO cells were inhibited. But no expression of hMLH(1) and hMSH(2)
      was observed. CONCLUSION: The above data showed both ATRA and PP had inhibitory
      effects on MS instability of cancer and thus demonstrated directly their
      beneficial role in stabilization of genomic DNA. However, the present authors
      have not observed any expression of hMLH(1) and hMSH(2) in RKO cells treated with
      ATRA or PP.

PMID- 12048676
TI  - [Mutation analysis of retinitis pigmentosa 1 gene in Chinese with retinitis
      pigmentosa].
AB  - OBJECTIVE: To investigate the frequency and pattern of RP1 point mutations in
      Chinese retinitis pigmentosa (RP) patients and to examine their effects on the
      development of RP. METHODS: Conformation sensitive gel electrophoresis (CSGE) and
      direct DNA sequencing were used to determine sequence alterations occurring in
      the entire coding region of the RP1 gene in 101 Chinese RP patients in Hong Kong.
      RESULTS: R677X was detected in one RP patient. A nonpathogenic nonsense mutation,
      R1933X, was identified in three normal individuals and one patient with Stargardt
      disease. The frequency of RP1 mutations among all RP patients in this study is
      1/101. R677X is expected to lead to large disruptions of the encoded protein.
      Additionally, 10 more missense alterations in the RP1 gene were identified in the
      subjects of this study. Apart from M479I whose pathogenicity can not be
      determined currently, other sequence changes are just polymorphisms of the RP1
      gene. CONCLUSION: The nonpathogenicity of R1933X indicates that the C-terminal
      224 residues of RP1 protein may be not critical for RP1. Recently, a C-termnal
      truncating mutation, Y1053(1 bp del), was reported to occur in an RP patient.
      Thus RP can be caused by lack of the region of RP1 protein after codon 1052 but
      before 1933. To confirm such a proposition, a large genotyping study is necessary
      and is likely to reveal more RP causative mutations and uncover more sequence
      alterations different from those of other ethnic groups.

PMID- 12048677
TI  - [A linkage disequilibrium study of methylenetetrahydrofolate reductase C677T and
      schizophrenia].
AB  - OBJECTIVE: To explore the relationship between the methylenetetrahy drofolate
      reductase (MTHFR) C677T missense mutation and schizophrenia by linkage
      disequilibrium study. METHODS: Linkage disequilibrium analys is was conducted bet
      ween MTHFR C677T and schizophrenia in 115 affected-sib-pair (105) and trios (10)
      families by XDT and MAPMAKER/SIBS soft system. The analyses were performed in
      different diagnostic categories and combined with the age of onset as well.
      RESULTS: No positive results were found in the analysis in all the family in all
      the four diagnostic categories. Significant P values, which were P<0.05, P<0.01
      respectively, were observed in the families with the affected individual's onset
      age less than 25 years in all the four diagnostic categories. CONCLUSION: The
      missense mutation of MTHFR C677T or other gene structure around this mutation may
      be one of the susceptibility gene of schizophrenia.

PMID- 12048678
TI  - [Influence of angiotensin II type 1 receptor gene polymorphism on patients with
      essential hypertension complicated by brain infarction].
AB  - OBJECTIVE: To identify the A1166/C polymorphism of angiotensin II type 1 receptor
      (AT1R) gene in patients with essential hypertension complicated with brain
      infarction (BI). METHODS: AT1R genotyping with polymerase chain reaction
      restrictive fragment length polymorphism was performed in 70 normotensive
      subjects, 72 hypertensive patients without cardio-cerebrovascular diseases(EH
      NCCVD) and 70 hypertensive patients with BI. The relationship between the
      polymorphism of AT1R gene and plasma lipid levels was also studied. RESULTS: The
      frequencies of C allele in the two groups of hypertension were higher than that
      in the health controls, respectively (P<0.05). But there was no significant
      difference in the frequency of C allele between the two groups of hypertension. A
      positive correlation was observed between the lipoprotein(a) and AT1R gene
      A1166/C polymorphism in hypertensive patients. CONCLUSION: AT1R gene contributes
      to the development of essential hypertensive, but not to the incidence of BI in
      the hypertensive.

PMID- 12048679
TI  - [Detection of fibroblast growth factor receptor 3 gene mutation at nucleotide
      1138 site in congenita achondroplasia patients].
AB  - OBJECTIVE: [corrected] To investigate the mutation at the transmembrane domain of
      fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying
      the major pathologic mechanism of achondroplasia (ACH) and to evaluate the
      efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening
      the point mutations. METHODS: The genomic DNA from 17 clinically diagnosed ACH
      patients where analysed by polymerase chain reaction-restriction fragment length
      polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR
      DGGE technique for screening. RESULTS: G to A transition mutation at nucleotide
      1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with
      Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All
      of the 14 samples with G to A mutation were also found to be positive for point
      mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP,
      implying that there was actually no point mutation in this amplified region.
      CONCLUSION: Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot
      point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a
      sensitive and reliable technique for point mutation screening, especially for the
      heterozygotes.

PMID- 12048680
TI  - [Relationship between the Nco I, Ava II polymorphism of low density lipoprotein
      receptor gene and atherosclerotic cerebral infarction].
AB  - OBJECTIVE To investigate the relationship between the Nco I, Ava II polymorphism
      of low density lipoprotein receptor (LDL-R) gene in patients with the occurrence
      of atherosclerotic cerebral infarction (ACI) among the Han nationality in
      Liaoning province. METHODS The polymerase chain reaction technique was used to
      study the polymorphisms of LDL-R gene and allele frequencies in 77 patients with
      ACI and in 113 age-matched Chinese healthy controls. The levels of the lipid and
      lipoproteins were also compared among the cases with ACI and the controls.
      RESULTS A(+) frequencies of LDL-R gene in healthy controls and ACI group were
      0.230 and 0.125 respectively, while the N(+) frequencies of healthy control and
      ACI group was 0.667 and 0.662 respectively. In case of the coexistence of A(-) A(
      ) and N(+) N(+), the relative risk (RR) of ACI was 5.56(P<0.001), while the RR of
      the increase of serum levels TG, TC, LDL-C, LP(a) were 4.29, 7.67, 9.33 and
      3.09(P<0.05), respectively. CONCLUSION The coexistence of A(-) A(-) and N(+) N(+)
      can affect the concentration of lipid and lipoprotein and is in close
      relationship with the occurrence of ACI.

PMID- 12048681
TI  - [Identification of genes associated with human osteosarcoma metastasis
      suppression using suppression subtractive hybridization].
AB  - OBJECTIVE: To identify genes associated with metastasis suppression and to
      investigate the molecular mechanism of osteosarcoma metastasis. METHODS: The
      subtracted cDNA library of low metastatic human osteosarcoma cell line SOSP-9607
      was constructed using suppression subtractive hybridization. Partial clones were
      sequenced. The acquired sequence data were aligned against the GenBank nucleotide
      database using Blastn to search for sequence matches. The interested clone was
      used to perform Northern blot and reverse transcriptase-PCR (RT-PCR) analysis on
      mRNA isolated from low metastatic cell line SOSP-9607 and OS-9901, high
      metastatic cell line SOSP-M and three pulmonic metastatic nodules of nude mice.
      RESULTS: A cDNA clone from low metastatic cell line SOSP-9607 subtracted cDNA
      library was identified as telomeric repeat binding factor 2 (TERF2) by sequence
      analysis and Blastn search. Northern blot and RT-PCR analysis demonstrated that
      TERF2 expressed highly in low metastatic cell line SOSP-9607 and OS-9901, but not
      in high metastatic cell line SOSP-M and three pulmonic metastatic nodules.
      CONCLUSION: TERF2 may be important for suppressing metastasis of osteosarcoma.

PMID- 12048682
TI  - [Effects of wild-type p53 gene on the chemotherapy sensitivity of ovarian cancer
      SKOV-3 cells to cisplatin].
AB  - OBJECTIVE: To assess the effect of wild-type p53 gene on the chemotherapy
      sensitivity of ovarian cancer SKOV-3 cells to cisplatin. METHODS: Recombinant
      eukaryotic expression vector pcDNA3 containing full-length human wild-type p53
      cDNA was introduced by lipofectamine-mediated gene transfection into SKOV-3
      cultured cells which were acted on by cisplatin of different concentrations. The
      chemotherapy sensitivity of tumor cells with different-status p53 was observed.
      RESULTS: The inhibitive rate of formation of clones after p53 cDNA transfection
      was 56.4% compared with the untransfected one. The formation of clones decreased
      by 76.2% and 84.1% respectively after being acted on by 0.5 ug/ml cisplatin for
      24 hours and 48 hours respectively. The formation of clones decreased by 89.5%
      and 93.7% respectively after being acted on by 1 ug/ml cisplatin for 24 hours and
      48 hours respectively. After the introduction of p53 cDNA, the S phase and the
      ratio of G(2)/M phase of tumor cells decreased, and the ratio of G(1)/G(0) phase
      increased. The introduction of p53 gene into cells led to cell cycle arrest in
      G(1) phase. CONCLUSION: The exogenous introduction of wild-type p53 cDNA into
      ovarian cancer SKOV-3 cells increased the chemotherapy sensitivity to cisplatin.

PMID- 12048684
TI  - [Effects of ectogenous FHIT gene on reversing malignant phenotype of human lung
      adenocarcinoma cells A549].
AB  - OBJECTIVE: To explore the role of fragile histidine triad(FHIT) gene in the
      proliferation, apoptosis and tumorigenesis of human lung cancer cells. METHODS:
      FHIT gene packaged with lipofectin was transfected into the cells of a human lung
      adenocarcinoma cell line (A549), which stably expressed ectogenous FHIT gene. The
      FHIT mRNA and protein expression of A549-FHIT, A549-vector and A549 cell were
      detected by reverse transcription-PCR(RT-PCR), Western blot and
      immunocytochemical methods. The cell cycle pattern and apoptosis were assayed by
      using flow cytometry. RESULTS: After transfection of FHIT gene, cell growth was
      obviously inhibited (P<0.01). The apoptosis index of A549-FHIT (8.42%) was
      significantly higher than that of A549-vector (5.45%) and A549 cells
      (5.71%)(P<0.01). The clone-formation rate of A549-FHIT cell (21.84%) was
      significantly lower than that of A549-vector (28.70%) and A549 cells (31.68%,
      P<0.01). Compared with control cell lines, larger scale of A549-FHIT cells
      accumulated in G0/G1, presenting that the proportion of the cells in G0/G1 phase
      was obviously increased from 67.78 % to 82.35 %. Tumorigenicity of the A549 cells
      in nude mice was greatly inhibited by expression of ectogenous FHIT gene, the
      weight and volume of A549-FHIT(1.61 g/1.37 cm(3)) were significantly lower than
      that of A549-vector (2.45 g/1.99cm(3)) and A549 cells (2.77 g/2.27
      cm(3))(P<0.05). CONCLUSION: Expression of ectogenous FHIT gene can obviously
      inhibit the proliferation and tumorigenesis of A549 cells, and can induce A549
      cells into programmed cell death. The result of this study suggests that FHIT
      gene may be a tumor suppressor gene in human lung cancer cells.

PMID- 12048683
TI  - [Linkage analysis of cytokine and cytokine-related receptor gene loci and
      essential hypertension in Chinese].
AB  - OBJECTIVE: To investigate the genetic linkage between several cytokine and
      cytokine-related receptor gene loci and essential hypertension (EH) in Chinese.
      METHODS: Linkage between seven genetic markers and EH in 95 Chinese nuclear
      families with EH (including 477 subjects) was analyzed using a technique of
      fluorescence-based gene scan with DNA short tandem repeat loci. These markers
      were selected from the chromosomal regions nearby eight cytokines and their
      receptor genes. The two-point non-parametric linkage analysis (NPL), maximum Lod
      score and transmission/disequilibrium test (TDT) with GENEHUNTER software package
      were used in this study. RESULTS: Result of TDT showed significant transmission
      disequilibrium between D14S61 and EH (Chi square 14.29,P=0.00016) although NPL
      and Lod score revealed no significant linkage (Z=0.78, P>0.05 and Lod score =0.72
      respectively) at this locus. No linkage between other loci typed and EH was found
      by the three genetic analysis methods (P>0.05 or Lod score<-1). CONCLUSION:
      Alleles at D14S61 were of significant transmission disequilibrium in affected
      siblings. Transforming growth factor beta 3 is 0.1 cM away from D14S61, which
      suggests that the relationship between genes at or near this regions and EH needs
      to be further explored.

PMID- 12048685
TI  - [Genetic polymorphism of 6 short tandem repeat loci in Chinese Korean].
AB  - OBJECTIVE: To analyze genetic polymorphism of D16S539 D7S820 D13S317 CSF1PO TPOX
      and TH01 in Chinese Korean. METHODS: One hundred unrelated individuals were
      analyzed by PCR amplification fragment length polymorphism analysis. RESULTS: Six
      alleles and 18 genotypes of D16S539 locus, 7 alleles and 22 genotypes of D7S820
      locus, 7 alleles and 23 genotypes of D13S317 locus, 6 alleles and 16 genotypes of
      CSF1PO locus, 6 alleles and 11 genotypes of TPOX locus, 5 alleles and 12
      genotypes of TH01 locus. CONCLUSION: The genotype distribution of all the 6 short
      tandem repeat(STR) in Chinese Korean met Hardy-Weinberg equilibrium, and have
      higher heterozygosities. The data obtained can be used in human identity and
      paternity testing, and in other genetic researches and population investigation.

PMID- 12048686
TI  - [Association of Pro12Ala variant in peroxisome proliferator-activated receptor
      gamma2 gene with type 2 diabetes mellitus].
AB  - OBJECTIVE: To investigate the association of Pro12Ala variant in peroxisome
      proliferator-activated receptor-gamma2 gene with type 2 diabetes mellitus and its
      clinical characteristics. METHODS: The genotypes of Pro12Ala variant in
      peroxisome proliferator-activated receptor-gamma2 gene were determined by
      polymerase chain reaction-restriction fragment length polymorphisms assay in 401
      unrelated subjects of the Han population in the southern part of China (including
      180 subjects with normal glucose tolerance and 221 type 2 diabetic patients). The
      clinical data were also analyzed. RESULTS: The allele frequencies in the case and
      control groups were 96.15%,96.11% for P and 3.85%, 3.89% for A; the genotype
      frequencies were 92.77%, 92.22% for PP, 6.78%, 7.78% for PA and 0.45%, 0 for AA.
      The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 was not
      significantly associated with type 2 diabetes. The Pro12Ala polymorphism of
      peroxisome proliferator-activated receptor-gamma2 in diabetes patients was
      associated with increased waist circumference and waist to hip ratio. The
      Pro12Ala polymorphism in Chinese population was similar to that in Japanese
      population and was different from that in European and American population.
      CONCLUSION: The above data showed that the Pro12Ala variant of peroxisome
      proliferator-activated receptor-gamma2 was not significantly associated with type
      2 diabetes, but it could be associated with abdominal obesity in type 2 diabetes.
      The significant difference of Pro12Ala of peroxisome proliferator-activated
      receptor-gamma2 among various races was observed.

PMID- 12048687
TI  - [Dystrophin detection by immunofluorescent technique for diagnosing muscular
      dystrophy].
AB  - OBJECTIVE: To establish a specific technique for diagnosing and classifying
      Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD),
      facioscapulohumeral muscular dystrophy (FSHD) and neurologic dystrophy. METHODS:
      Forty-seven cases were detected by immunofluorescence technique for analyzing
      dystrophin located in skeletal muscle cell membrane with the use of mouse
      monoclonal antibodies, goat and rabbit polyclonal antibodies. RESULTS: The normal
      individuals showed ringed positive staining stripe around muscle fibers. Negative
      result of staining was seen in 16 DMD patients. Eleven BMD patients had
      discontinuous or a patchy positive staining pattern, and all of 10 FSHD and 10
      neurological amyotrophic patients showed positive dystrophin staining.
      CONCLUSION: Detecting dystrophin in the skeletal muscle cell membrane of muscular
      patients is an efficient technique for diagnosing and classifying various types
      of muscular dystrophy.

PMID- 12048688
TI  - [The detection of the frequent mutations of iduronate-2-sulphatase gene in
      mucopolysaccharidosis type II patients in Chinese].
AB  - OBJECTIVE: To investigate and establish the gene diagnosis methods for the
      frequent mutations of iduronate-2-sulphatase(IDS) gene in mucopolysaccharidosis
      type II patients. METHODS: polymerase chain- reaction-single strand conformation
      polymorphism PCR-SSCP) analysis was applied to detect the mutations of exons 3, 8
      and 9 which were hot spots in the iduronate-2-sulfatase gene; DNA sequencing was
      applied to analyze the mutations which had been detected by PCR-SSCP; PCR
      restriction fragment length polymorphism (PCR-RFLP) was applied to detect the
      results of DNA sequencing. RESULTS: Obvious and abnormal bands in exon 9 of the
      IDS gene were found by applying PCR-SSCP; the mutation(C1672T) of exon 9 was
      found in the patient through DNA sequencing, which led to amino acid
      replacement(R468W); the PCR-restriction enzyme digestion showed that only one
      band(554 bp) appeared in the patient, but there were two bands (257 bp and 297
      bp) in his parents, and it verified the results of sequencing analysis.
      CONCLUSION: PCR-SSCP analysis, DNA sequencing analysis and PCR-restriction enzyme
      digestion are effective methods for MPS II diagnosis. Combined applications of
      these methods can verify and complement each other and improve the accuracy of
      diagnosis.

PMID- 12048689
TI  - [Molecular genetics and clinical application of Rh blood group system].
AB  - The Rh blood group system is one of the most complex and important systems known
      in humans. It has two homologous structure genes in tandem on 1p34.3-36.1 that
      encode Rh protein. The Rh protein is a membrane in red blood cell that has 12
      transmembrane spans. Rh antigens have many variants; there are three genetic
      polymorphisms in the RhD-negative individual. The Rh blood group system is of
      great significance in clinical transfusion and hemolytic disease of the newborn
      (HDN). Rh PCR genotyping is used for prenatal diagnosis in fetus, but still it
      has some defects, and in this connection further knowledge about Rh system will
      be necessary to solve the problem.

PMID- 12048691
TI  - Porous orbital implants and their behaviour during drilling.
AB  - The use of porous spherical orbital implants enables ocular prosthesis motility
      to be improved if necessary by subsequent drilling of the implant and coupling it
      to the prosthesis with a peg. We compared the effect of drilling at different
      speeds on hydroxyapatite and porous polyethylene (Medpor) spherical implants. The
      implants were drilled at fixed speeds of between 15 and 2000 revolutions per
      minute. The samples were then viewed in an electron microscope and photographed.
      When hydroxyapatite is drilled the porous structure of the implant is maintained
      although a precise hole with well-defined walls was not produced. This contrasts
      with porous polyethylene where the porous structure is lost although a precise
      drill hole is created. This drilling technique has been used successfully in
      patients with hydroxyapatite implants, thus making possible stable
      epithelialisation of the drill hole. Our results confirm that the drilling of
      porous polyethylene using this technique is unlikely to be successful, as loss of
      the porous structure would prevent stable epithelialisation of the drill hole,
      resulting in exposure of the implant. 

PMID- 12048690
TI  - [Preimplantation genetic diagnosis].
AB  - Preimplantation genetic diagnosis is a very early form of prenatal diagnosis
      aimed at eliminating embryos carrying serious genetic diseases before
      implantation. The basic techniques currently used involve embryo biopsy, the
      polymerase chain reaction and fluorescence in situ hybridization. In the current
      review, a number of problems arising from the use of these technologies as well
      as the possible solutions and new developments are discussed.

PMID- 12048692
TI  - The role of enophthalmos in the development of involutional ectropion.
AB  - PURPOSE: This prospective study was performed to evaluate whether there is an
      association between enophthalmos and involutional ectropion. METHODS: Hertel
      exophthalmometric measurements were obtained from 31 patients with involutional
      ectropion and from 30 control patients who were age- and sex-matched. RESULTS:
      Eighteen patients had bilateral ectropion and 13 patients had unilateral
      ectropion. The mean of the exophthalmometric measurements of the eyes with
      ectropion was 12.67 +/- 2.48 (SD) mm. The mean of the exophthalmometric
      measurements of the control patients was 12.80 +/- 2.87 (SD) mm in the right eye
      and 12.83 +/- 2.93 (SD) mm in the left eye. The difference between the eyes of
      the patients and the controls was not statistically significant (p>0.05). In the
      affected eyes of the patients with unilateral ectropion, the mean
      exophthalmometric value was 13.15 +/- 2.51 (SD) mm, and in the unaffected eyes of
      the patients, the mean exophthalmometric value was 13.07 +/- 2.56 (SD) mm. This
      difference was not statistically significant either (p>0.05). CONCLUSION:
      Patients with involutional ectropion do not have more enophthalmos than the age-
      and sex-matched normal population. This study does not suggest an association
      between enophthalmos and involutional ectropion. 

PMID- 12048693
TI  - Small margin (2 mm) excision of peri-ocular basal cell carcinoma with delayed
      repair.
AB  - Successful surgical treatment of peri-ocular basal cell carcinomas requires
      complete excision. Mohs' micrographic surgery achieves this, but is not readily
      available in all hospitals. The standard 3-4 mm margin does not guarantee
      complete excision and histology is often not available until after a repair has
      been undertaken. The 3-4 mm margin has evolved to deal with all forms of BCC. In
      our opinion, this margin is unnecessarily large for nodular/ulcerative BCC. We
      report our interim results of excision of localised BCCs using a 2 mm margin in
      conjunction with a delayed repair following confirmation of histological
      clearance. Thirty-one patients were treated in this manner; there have been no
      recurrences after an average follow-up period of 36 months (range 24-57 months). 

PMID- 12048694
TI  - Precursor B-cell lymphoblastic lymphoma presenting as an orbital mass.
AB  - A previously healthy 12-year-old boy presented with acute onset of proptosis of
      his left eye. CT scan demonstrated a mass involving the left orbit, left
      maxillary sinus, and left ethmoid sinus with extension through the cribriform
      plate into the anterior cranial fossa. Incisional biopsy of the mass revealed a
      precursor B-cell lymphoblastic lymphoma. Precursor B-cell lymphoblastic lymphoma
      is a rare type of non-Hodgkin's lymphoma seen exclusively in children and young
      adults. This is the first reported case of precursor B-cell lymphoblastic
      lymphoma presenting in the orbit. Treatment is primarily by systemic chemotherapy
      and is potentially curative. The principal role of the ophthalmologist is in
      diagnosis and monitoring of such patients. The clinical features and
      multidisciplinary diagnosis and management of childhood non-Hodgkin's lymphomas
      are reviewed. 

PMID- 12048695
TI  - Orbital giant cell fibroblastoma.
AB  - BACKGROUND: This report describes the clinical and morphologic (light and
      electron microscopic and immunohistochemical) features of orbital giant cell
      fibroblastoma which, to the best of our knowledge, has not been reported before
      in the ophthalmological literature. METHODS: Clinical symptoms, computed
      tomography (CT), and magnetic resonance (MR) features, light and electron
      microscopic and immunohistochemical findings were reviewed in a 65-year-old woman
      who developed an orbital giant cell fibroblastoma. RESULTS: The patient presented
      with a large, infiltrating, intra- and periorbital mass, causing severe
      proptosis, ocular displacement, and visual loss on the left side. CT and MR
      imaging demonstrated a large, irregular tissue density in the orbit leading to
      displacement of the globe anteriorly and inferolaterally. With T(1)-weighted MR
      images, the lesion was isointense to the gray matter of the brain and revealed
      marked enhancement with Gd-DTPA. Histopathologically, the tumor consisted of a
      mixture of spindle and multinucleated giant cells scattered within a myxomatous
      stroma. CONCLUSION: Giant cell fibroblastoma, a benign mesenchymal tumor of
      infancy, is rarely encountered within the orbital region. This lesion is
      considered to be a distinct, non-metastasizing tumor, but its clinical management
      may be very difficult, as in our case, because of its invasive nature and
      potential for recurrence. 

PMID- 12048696
TI  - Primary liposarcoma of the orbit: a clinicopathological study.
AB  - Primary liposarcoma of the orbit is a rare tumour. There are very few cases of
      orbital liposarcoma reported in the literature, mostly of the myxoid variety. In
      this paper, the authors report the clinical presentation, histopathological
      features, results of diagnostic studies and management of a case of orbital low
      grade myxoliposarcoma with local recurrence, together with a review of the
      literature. 

PMID- 12048697
TI  - Neglected malignant medulloepithelioma of the eye.
AB  - Intraocular medulloepithelioma is a rare tumor usually arising from the ciliary
      body and presenting in childhood. We recently managed a case of an advanced
      medulloepithelioma in a 45-year-old man that went untreated for several years.
      The patient had an exenteration after the tumor destroyed the eye and extended
      into the central nervous system. The initial pathologic diagnosis was complicated
      by the undifferentiated nature of the tumor which mimicked a lymphoma on fine
      needle aspiration biopsy (FNAB) as well as on initial permanent sections. The
      diagnosis was established by immunohistochemical stains indicating a
      neuroepithelial origin; the relationship of the tumor to the ciliary body and
      pigmented ciliary epithelium indicated the site of origin. 

PMID- 12048699
TI  - Surgical correction of entropion and excess upper eyelid skin in congenital cutis
      laxa: a case report.
AB  - Congenital cutis laxa is a rare generalized inherited elastosis, characterized by
      the appearance of premature aging and skin laxity with mild to severe systemic
      anomalies. Ocular manifestations include excess skin in the eyelids, ptosis and
      lower lid ectropion. Of the hyperelasticity syndromes - Ehlers Danlos,
      Pseudoxanthoma elasticum and cutis laxa - only cutis laxa has normal skin wound
      healing. The diagnosis must therefore be established before surgical options for
      treatment are considered. We report an unusual case of a 5-month-old male child
      with cutis laxa who presented with upper lid entropion secondary to severe
      redundant upper eyelid skin. An anterior lamellar repositioning procedure
      successfully corrected the lid margin malposition with complete relief of
      symptoms. 

PMID- 12048698
TI  - Merkel cell tumour: case reports and review.
AB  - Merkel cell carcinoma, a small-cell undifferentiated/neuroendocrine carcinoma, is
      a highly invasive primary malignant neoplasm of the skin that may arise from
      Merkel cells or an epithelial precursor cell. One tenth of all cases affect the
      eyelids and periocular region, typically in the elderly population. The
      presentation is generally as a painless erythematous nodule with telangiectatic
      blood vessels and often intact overlying skin. The rarity of Merkel cell
      carcinoma of the eyelid can lead to delay in diagnosis and treatment of this
      tumour. In the present paper, the authors illustrate the aggressive nature of
      Merkel cell carcinoma, and the importance of early and wide surgical treatment
      and close follow-up. They discuss the role of rapid paraffin histology compared
      to frozen section. METHODS: Three cases are described, discussing the clinical
      presentation, diagnosis and treatment, with a review of the pathology. RESULTS:
      All three patients were female, presenting with rapidly growing upper eyelid
      tumours 20 mm in size; one case had paraffin sections suggesting incomplete
      clearance when frozen section had appeared clear; exenteration was required. The
      other two cases had lymph node involvement at one and two months post wide local
      excision. All patients remain alive at follow-up of 6, 4.6, and 2 years,
      respectively. DISCUSSION: The cases illustrate the aggressive nature of the
      tumour, the unusual tarsal involvement and the typical pathology. Sampling errors
      associated with limited frozen section control of excision may be avoidable by
      the use of rapid paraffin histology. The highly invasive nature of this tumour
      requires close follow-up following resection. 

PMID- 12048701
TI  - Suspicion, speed, sufficiency and surgery: keys to the management of orbital
      infections.

PMID- 12048700
TI  - Factors affecting the success rate of the Quickert and Wies procedures for lower
      lid entropion.

PMID- 12048702
TI  - Bacterial infections of the orbit.
AB  - This review of the literature on orbital infections focusses on bacterial
      infections of the preseptal space, subperiosteal abscesses, orbital phlegmon and
      orbital abscesses. The need for a timely diagnosis of and multidisciplinary
      approach to treatment of these infections, which may lead to life-threatening
      complications, is emphasized. 

PMID- 12048703
TI  - Rhino-orbital-cerebral mucormycosis: a review.
AB  - Rhino-orbital-cerebral mucormycosis (ROCM) is an acute, often fatal, fungal
      infection caused by members of the class Zygomycetes and the order Mucorales. The
      genus Rhizopus accounts for most cases of ROCM. The disease is characterized by
      fungal hyphal invasion of blood vessels resulting in thrombosis and infarction of
      the nasal, paranasal sinus, orbital, and cerebral tissues. The most commonly
      associated condition is diabetes mellitus; other associated conditions include
      immunocompromised states, renal disease, deferoxamine use, and acidotic states.
      Common clinical findings include rhinitis, periorbital and facial swelling,
      facial and mucosal necrosis, ophthalmoplegia, multiple cranial nerve palsies,
      facial pain, and headache. Definitive diagnosis is made by demonstration of
      fungal hyphae in tissue specimens. The mainstay of treatment is aggressive
      surgical debridement of infected tissue and administration of amphotericin B.
      ROCM has a mortality rate of 40-50%; 70% of survivors are left with residual
      defects. Early diagnosis and treatment are imperative in the successful
      management of patients afflicted with this devastating sight- and life
      threatening disease. 

PMID- 12048704
TI  - Diagnosis and management of orbital inflammation and infections secondary to
      foreign bodies: a clinical review.
AB  - Orbital inflammation and secondary infections may be caused by many types of
      foreign bodies, including organic and inorganic matter, non-autogenous surgical
      implants and allografts, and surgical hardware and materials utilized in
      reconstructive surgery. In penetrating injury patients, the nature of the foreign
      body determines the clinical behavior; inert objects such as steel and glass may
      not cause significant inflammation to warrant their removal. Removal of organic
      foreign bodies, however, is mandatory since these objects usually lead to
      secondary infection with abscess and fistula formation. This paper reviews
      salient points related to history-taking and physical examination, diagnostic
      workup, and medical and surgical treatment in foreign body-induced orbital
      inflammation and infections. It is emphasized that practically every case of
      orbital trauma should be approached with a high index of suspicion for
      penetrating injury with possible intraorbital foreign body. The investigational
      tools to detect orbital foreign bodies, including ultrasonography, computed
      tomography and magnetic resonance imaging, are reviewed. The principles of the
      management, including antimicrobial therapy, surgical indications and techniques,
      are also discussed. 

PMID- 12048705
TI  - Ultrasonological characteristics of extraocular cysticercosis.
AB  - Cysticercosis is a common ophthalmic parasitosis wherein humans are the
      intermediate hosts in the life cycle of the tape worm Taenia solium. While
      intraocular cysticercosis is more common and is more readily diagnosed
      clinically, recognition of extraocular cysticercosis needs supplementary imaging.
      Computed tomography (CT) and magnetic resonance imaging (MRI) have been
      extensively used to diagnose and characterize neurocysticercosis. Since the orbit
      is easily accessible to ultrasonography (USG), we evaluated its role in the
      diagnosis and management of extraocular cysticercosis. Serial A- and B- scan
      ultrasonograms from 24 patients with extraocular cysticercosis were analyzed to
      determine features at various stages of evolution of the lesion and an attempt
      was made to classify the lesion on this basis. Of 24 patients, 23 had a cyst
      clearly demonstrable by USG: 22 within or attached to an extraocular muscle (with
      or without myositis) and one free in the orbit. One patient had an optic nerve
      cyst not detected by USG but by CT scan. Cysts at various stages of evolution
      were found - viable, degenerating and inactive. The therapeutic response of the
      cyst to treatment with oral albendazole could be effectively studied and
      monitored by sequential USG. Orbital ultrasound is a practical, precise and cost
      effective imaging modality to diagnose, manage and monitor extraocular
      cysticercosis, although it can not completely replace CT and MRI. 

PMID- 12048706
TI  - Three cases of isolated mucoceles and one case of an Aspergillus infection in the
      sphenoid sinus with orbital signs and symptoms.
AB  - Four patients with an isolated sphenoid lesion: three with a mucocele and one
      with an Aspergillus infection of the sphenoid sinus in whom the orbital
      impairment had a rhinogenic cause, are described. They all presented with one or
      more of the following features: visual loss, motility disturbances, visual field
      defects, and sensitivity loss of the infraorbital nerve. In one patient, optic
      disc edema was seen. Diagnostic imaging technologies such as computer tomography
      (CT) and magnetic resonance (MRI) make an early diagnosis possible but
      nevertheless, very large mucoceles with major functional loss were detected at a
      late stage of the disease. The Aspergillus infection was detected at an early
      stage without delay because of its specific appearance on CT and MRI. The signs
      and symptoms of these lesions are more striking in the orbital and neuro
      ophthalmological field than in the ear-nose-throat (ENT) field, but nevertheless,
      primary treatment should be marsupialization by an ENT-surgeon. 

PMID- 12048707
TI  - Malignant orbital and orbitomaxillary tumors: surgical considerations.
AB  - Malignant tumors of the orbit and the orbitomaxillary region constitute 4-8% of
      head and neck malignancies. The lesions can be primary orbital malignant tumors
      or can invade the orbit from the eyelids, the eyeball or the paranasal sinuses,
      especially the maxillary sinus and ethmoids. The commonest primary malignant
      tumors of the orbit are lymphomas, rhabdomyosarcomas and lacrimal gland
      epithelial tumors. These tumors are excluded from the present study since their
      management differs from that of metastatic tumors. Our experience is based on a
      series of 48 patients operated during the last five years. There was an equal
      distribution according to both age and sex, with two-thirds of the patients being
      over 60 years of age. Histologically, the basal cell carcinomas (B.C.C.)
      prevailed with 19 cases, followed by squamous cell carcinomas (Sq.C.C.) in 12,
      adenocarcinomas (AdenoCa) in 10 and orbital melanomas (O.M.) in 7. In 13 cases
      the maxilla was also affected. Surgical treatment varied from exenteration to
      wide cran iofacial resections; immediate reconstruction followed in all cases.
      Only 10 patients were treated with surgery alone. In the remaining 38 patients
      radiotherapy was given, alone or in combination with chemotherapy. The surgical
      techniques included exente ration with split-thickness skin grafting in 19 cases,
      exenteration with coverage with median forehead flap in 16, and maxillectomy with
      forehead and temporalis flaps in 7 cases. The tumors recurred in 12 patients, all
      of them in the first postoperative year. Ten patients died from intracranial
      involvement or distant metastases. In six of these patients the lesions were
      Sq.C.C., in two AdenoCa and in two O.M. It is concluded that the surgical
      treatment of orbital and orbitomaxillary malignancies, although subject to broad
      guidelines that determine the operability of the tumors, should be individualized
      according to the extent of the lesion and the experience of the surgeon. 

PMID- 12048708
TI  - Loss of heterozygosity on the long arm of chromosome 11 in orbital embryonal
      rhabdomyosarcoma (OERMS): a microsatellite study of seven cases.
AB  - OBJECTIVES. To investigate, by means of microsatellite analysis, regions of
      chromosome 11 involved in the genesis of embryonal rhabdomyosarcoma (ERMS)
      localized to the orbit. METHODS. Microsatellite analysis was carried out on seven
      cases of orbital ERMS by comparing the electrophoretic migration patterns of PCR
      amplified microsatellites of chromosome 11 from both constitutional (blood) and
      tumor genotypes. Five of the tumors analyzed were samples frozen at the time of
      surgery, and two were paraffin embedded. RESULTS. Overall, microsatellites
      D11S1396 (11q13.1-q22.3) and D11S976 (11q) showed loss of heterozygosity (LOH) in
      all tumor samples, thus indicating the presence, on the long arm of chromosome
      11, of one or more tumor suppressor genes with a possible role in the genesis of
      the disease. CONCLUSION. While the role of genes on the short arm of chromosome
      11 in the genesis of ERMS is well established, much less is known of the possible
      involvement of tumor suppressor genes on the long arm of the same chromosome.
      This is the first report showing the possible involvement of tumor suppressor
      genes in this portion of the chromosome in ERMS localized to the orbit. 

PMID- 12048709
TI  - Bilateral orbital involvement in Erdheim-Chester disease.
AB  - Erdheim-Chester disease is an idiopathic condition characterized by a
      xanthogranulomatous process infiltrating the bones, lungs, heart, retroperitoneum
      and other tissues. This condition is often fatal. Ocular findings are rare. The
      authors report a case of bilateral xanthelasmas and bilateral massive orbital
      infiltration in a 61-year-old man with severe retroperitoneal fibrosis, renal and
      cardiovascular problems. The ophthalmic manifestations and differential diagnosis
      of this peculiar pathologic condition are discussed. 

PMID- 12048710
TI  - Orbital hydatid cyst: an unusual presentation.
AB  - PURPOSE. To describe an unusually large and long-standing hydatid cyst of the
      orbit causing gross disfigurement of the eyeball. METHODS. Detailed
      investigations, consisting of radiological and hematological studies, were
      carried out to determine the cause of the unusually severe and long-standing
      proptosis. The patient underwent orbital exploration for the presumed diagnosis
      of orbital echinococcosis.The entire cyst with the globe was removed and sent for
      histopathological examination. RESULTS. The gross and histopathological findings
      of the specimen removed surgically confirmed the diagnosis of orbital hydatid
      cyst. CONCLUSION. The diagnosis of orbital hydatid cyst should be considered in
      unilateral severe proptosis of long duration with gross disfigurement of the
      globe and orbital walls. 

PMID- 12048711
TI  - Lacrimal gland involvement in Kikuchi-Fujimoto disease.
AB  - PURPOSE. A 32-year-old Saudi female presented with typical Kikuchi-Fujimoto
      disease, i.e., fever, cervical lymphadenitis and leukopenia, but there was also
      painful upper eyelid swelling with pain on upgaze. METHODS. A connective tissue
      disease and lymphoma workup were unremarkable, as were antibody titers to Apifia
      felis and Bartonella henselae. RESULTS. Orbital computed tomography showed
      significant lacrimal gland enlargement. Cervical node biopsy revealed necrotizing
      lymphadenitis. CONCLUSION. Concomitant lacrimal gland inflammation and cervical
      lymphadenopathy may be a benign self-limited disease. 

PMID- 12048712
TI  - Combined treatment of periorbital arteriovenous malformation: a case report.
AB  - A 54-year-old woman had a gradually growing subcutaneous mass for more than three
      decades over her right zygomatic bone and below the right inferior orbital rim.
      The tumor was slightly pulsatile and non-tender. MRI scans demonstrated an
      unusually vascularized soft tissue mass with many large-caliber vessels.
      Selective angiography showed the mass to be an arteriovenous malformation with
      the principal feeder being the internal maxillary artery. A combined treatment
      scheme which consisted of an initial embolization of the lesion followed by
      surgical extirpation was carried out. This sequential approach allowed safer
      surgery and a satisfactory cosmetic outcome. 

PMID- 12048713
TI  - MRI features of craniofacial fibrous dysplasia.
AB  - A 13-year-old female with a 4-year history of monostotic fibrous dysplasia had
      noticed a progressive proptosis of the right eye and diplopia on upward gaze for
      4 weeks. A few years previously an incisional biopsy of the skull had verified
      the presumed diagnosis of fibrous dysplasia with recurrent bleeding into
      pathologic cystic bony structures of the skull. The patient was known to have
      craniofacial fibrous dysplasia with involvement of the frontal and intermediate
      cranial base, the posterior ethmoidal labyrinth, and the sphenoidal and maxillary
      sinuses. Eye examination showed a reduced visual acuity in the right eye without
      defects of the visual field. MR imaging showed a fluid-filled cystic cavity in
      the orbital frontal bone pushing the globe downwards. Four months later she
      developed similar symptoms on the other side while proptosis of the right eye was
      regressive. T2-weighted MRI revealed a large fluid-filled cystic cavity with a
      fluid-fluid level in the upper part of the left orbit. It is concluded that
      follow-up studies can be easily performed by MRI without additional exposure to
      radiation. The total extent of osseous involvement can be determined. Thus, MRI
      may be helpful in deciding between operative or conservative therapy. 

PMID- 12048714
TI  - Radionuclide dacryocystography.
AB  - Radionuclide dacryocystography (RNDCG) is a safe, physiologic method of
      evaluating lacrimal drainage. The technique is performed by placing a radioactive
      "tear" in the eye(s) and following the passage of radioactivity through the
      lacrimal drainage apparatus with a scintillation (gamma) camera. RNDCG is
      indicated in any patient with tearing who has a lacrimal drainage system which is
      open to irrigation. It is also useful in children, when clinical signs are
      equivocal. Interpretation is made by comparing a patient's scan to "normal"
      scans, or in unilateral cases, by comparing the symptomatic side to the
      asymptomatic side. Many causes of functional or partial lacrimal drainage
      obstruction can be detected and differentiated from various tear hypersecretion
      abnormalities. RNDCG also has many research applications. 

PMID- 12048715
TI  - Proximal canalicular imaging utilizing ultrasound biomicroscopy A: Normal
      canaliculi.
AB  - The proximal canaliculi are the most difficult structures within the lacrimal
      drainage pathways to be imaged. Dacryocystography has been the most useful method
      for imaging the canaliculi, but it cannot demonstrate the canaliculi distal to an
      obstruction, nor can it demonstrate the walls or tissue surrounding the walls of
      the canaliculi. Ultrasound biomicroscopy utilizing a high-resolution subsurface
      imaging technique is able to image the proximal canaliculi in the cadaver model. 

PMID- 12048716
TI  - Proximal canalicular imaging utilizing ultrasound biomicroscopy B: Canaliculitis.
AB  - The proximal canaliculi can be imaged in patients with canaliculitis utilizing
      ultrasound biomicroscopy. The caliber of the proximal canalicular lumina, dilated
      by the disease process, can be evaluated. In addition, stones, debris and tissue
      fluid may be visualized within the system, without the need to inject a viscous
      material. This technique may prove to be of value in patients with mild or
      subclinical canaliculitis from the perspective of diagnosis. Outlining the extent
      of the disease process within the canaliculus may have some therapeutic value as
      well. 

PMID- 12048717
TI  - Proximal canalicular imaging utilizing ultrasound biomicroscopy C Experimental
      balloon catheter dilatation.
AB  - If proximal canalicular obstruction is to be treated by balloon catheter
      dilatation, a technique must be available to measure the short-term and long-term
      effects of the dilatation. Ultrasound biomicroscopy can image the pre-dilated and
      post-dilated proximal canaliculus in vivo. Further in vivo studies will determine
      the potential of this technique in the clinical setting. 

PMID- 12048718
TI  - Ocular injuries in midfacial fractures.
AB  - The incidence of ocular lesions in midfacial fractures ranges from 4 to 67%,
      depending on the criteria used in the previous examination. We report a
      retrospective study of 219 patients (233 fractures) who were admitted to our
      hospital between January 1990 and June 1994. The fractures are classified
      according to Henderson's classification (X-ray and Computed Tomography). We
      present the results of the ophthalmologic evaluation, after excluding palpebral
      lesions, and discuss the correlation with the etiology and the kind of fracture.
      The ocular lesions are divided into extraocular and intraocular ones. The
      extraocular lesions that we found are the following: damage to the lacrimal
      system, cranial nerve damage, displacement of the eye, corneal erosion and
      corneal foreign body and conjunctival lesions (subconjunctival hemorrhages,
      lacerations and chemosis). The intraocular lesions studied are divided into
      lesions of the anterior structures (hyphema, traumatic cataract, lens dislocation
      and hernia of the iris) and lesions of the posterior structures (vitreous and
      macular hemorrhage, eyeball perforation, optic nerve damage and Berlin's edema).
      Our conclusion is that comminuted fractures, fractures of the orbital rim only
      and those of the orbital floor are the most frequently associated with ocular
      damage, being mainly caused by automobile accidents and assaults. 

PMID- 12048719
TI  - Phakomatous choristoma of the orbit.
AB  - Phakomatous choristoma is a rare adnexal congenital tumor of lenticular anlage.
      The authors performed a standard orbital tomography of the orbits for the
      evaluation of a mass that was palpable in the left lower eyelid of a 3-month-old
      boy. Hematoxylin-eosin, special stainings and immunohistochemistry were performed
      on the excised mass. The histopathological and immunohistochemical findings
      confirmed the diagnosis of phakomatous choristoma. The CT scans showed that the
      mass was located in the orbit. Even though phakomatous choristoma is usually
      reported as a lower eyelid lesion, the orbital localization offers a better
      explanation for the chronological embryonic origin of this rare pediatric tumor. 

PMID- 12048720
TI  - Metastatic pancreatic islet cell carcinoma to the orbit: a case report.
AB  - We report a rare case of pancreatic islet cell carcinoma metastatic to the orbit
      in a 29-year-old woman. The initial symptomatology, progression of the disease,
      and radiologic and histopathologic findings are presented and discussed. 

PMID- 12048721
TI  - The place of transsaccal dacryocystorhinostomy in modern lacrimal surgery.
AB  - Despite the advances in transnasal and external dacryocystorhinostomy,
      transsaccal dacryocystorhinostomy is an excellent addition to the armamentarium
      in chronic fistulizing dacryocystitis with a dilated tear sac in elderly
      patients. A large incision with excision of the fistula opens the lacrimal sac,
      from where a wide dacryocystorhinostomy can be opened into the nose. The skin and
      tear sac incision can be closed in one layer. 

PMID- 12048722
TI  - Lacrimal drainage capacity, age and blink rate.
AB  - PURPOSE: The aim of this study was to investigate the influence of blink rate on
      lacrimal drainage capacity in different age groups. METHODS: The drop test for
      lacrimal drainage capacity was recently described by us. In the drop test, drops
      of 10 &mgr;l, 15 &mgr;l or 20 &mgr;l of lukewarm saline are repeatedly instilled
      in the tear film during three minutes. Excessive saline solution is then removed
      and the volume drained by the lacrimal passages is calculated. The drop test was
      performed in 40 individuals of two age groups, 10-30 years and 60-80 years. The
      drop test results were recorded when the subjects tried to blink at frequencies
      of 90 and 180 blinks/three minutes. RESULTS: The drop test results were
      significantly higher in the young than in the old subjects. At the lower blink
      rate, the lacrimal drainage capacity was 363 &mgr;l/3 min. in the young and 155
      &mgr;l/3 min. in the old subjects. At the higher blink rate, the lacrimal
      drainage capacity was 520 and 200 &mgr;l/3 min., respectively. The increases in
      lacrimal drainage capacity with increasing blink rate were significant in both
      age groups. CONCLUSION: The lacrimal drainage capacity increased with increasing
      blink rate in both younger and older subjects. The lacrimal drainage capacity was
      significantly lower in the old age group at each blink frequency, indicating that
      other factors than blink rate are responsible for the lower lacrimal drainage
      capacity in older age. 

PMID- 12048724
TI  - Factors affecting the success rate of the Quickert and Wies procedures for lower
      lid entropion.
AB  - Many different surgical procedures have been described for the treatment of
      involutional lower lid entropion. Two commonly performed operations, namely, the
      Wies and Quickert procedures were analysed to assess the success rates and the
      factors responsible for their failures. The failure rates were 26% and 5% for the
      Wies and Quickert procedures, respectively. Most of the failures in these
      procedures were attributed to untreated lid laxity and the mean time of
      recurrence was 8 months. We therefore stress the importance of careful lid
      examination, in particular for horizontal lid laxity, as this will influence the
      choice of surgical procedure and ultimately the success of treatment. 

PMID- 12048723
TI  - Radiation absorption properties of orbital implants.
AB  - PURPOSE: To determine the radiation absorption properties (RAP) of three commonly
      used orbital implant materials, namely, methylmethacrylate (MM), hydroxyapatite
      (HA), and porous polyethylene (PP). METHODS: Eighteen (18)-mm spheres of MM, HA
      and PP were tested with 1.25 MV gamma-rays from cobalt-60, 6 MV X-rays, and 9
      MeV, 12 MeV, and 16 MeV electron beams. The implants were immersed in a water
      phantom, and the measurements were obtained on X-omat V(R) film; the scanning was
      done with a computerized laser densitometer, CADSCAN(R). RESULTS: The RAP of all
      three materials appeared to be very close to those of water. The density of the
      MM implant was calculated to be the closest to that of water at all photon and
      electron energies. PP had a higher transmission than water at all electron
      energies (9, 12 and 16 MeV); the transmission through HA, however, was lower than
      through water. CONCLUSION: When postoperative radiation is indicated for an orbit
      containing an implant, the RAP of the allograft material play a significant role
      in the planning of the radiation treatment. Our study indicated that MM implants
      have RAP equivalent to those of water when treatment of orbital tumors is
      undertaken at the commonly used photon and electron energies. The RAP of the
      other allografts were either higher or lower, which may lead to unreliability in
      irradiation planning. 

PMID- 12048725
TI  - Botulinum toxin as adjunct for refractory compressive optic neuropathy in Graves'
      disease.
AB  - An euthyroid patient was referred for compressive optic neuropathy in Graves'
      disease. Under prednisone therapy the right and left visual acuities were 1.0 and
      0.4, with a profound decrease in color vision on the left. Bilateral anterior
      orbital decompressions were performed. When prednisone was withdrawn
      postoperatively, the visual acuity of the right eye dropped to 0.32 with
      bilateral complete failure on the Ishihara color test. A biopsy of the inferior
      oblique muscle of the left eye confirmed Graves' disease and additional
      transantral decompression of the right orbital apex was performed. Under
      intravenous methylprednisolone therapy, the visual acuity dropped postoperatively
      to 0.2 and 0.4, respectively. 15 U botulinum toxin were given by retrobulbar
      injection between the inferior and lateral rectus muscles. Four days later the
      patient called and said that the visual acuity in the right eye had improved
      tremendously. Two weeks after the injection the visual acuity was 0.7 in both
      eyes, although prednisone had been reduced to 20 mg by that time. The convergent
      strabismus had increased but the already severely restricted motility of the
      right eye had been little affected by the retrobulbar injection, and adduction
      not at all. Orbital CT-scan showed thinning of the inferior and lateral rectus
      muscles, but not of the medial rectus. 

PMID- 12048726
TI  - Lacrimal gland hemangiopericytoma.
AB  - A 45-year-old man and a 21-year old man presented with palpable lacrimal gland
      fossa masses and mechanical ptosis and proptosis, respectively. Computed
      tomography demonstrated well-circumscribed, partially cystic tumors. Echography
      in one case showed a well-outlined, predominantly low-reflective lesion with
      cysts and moderate vascularity detected by Doppler flow and standardized A-scan
      studies. Histopathology of the excised tumors revealed them to be CD34 antigen
      positive hemangiopericytomas, in one case associated with lacrimal gland ductal
      cysts (dacryops) and with cyst-like spaces containing proteinaceous exudate in
      the other. No recurrence was found at 14 and 30 months, respectively. Although
      uncommon, hemangiopericytomas should be included in the differential diagnosis of
      lacrimal gland tumors. Orbital ultrasound revealing vascularity may be a useful
      adjunct in this diagnosis. Cystic degeneration or dacryops due to tumor
      infiltration and compression of lacrimal gland ducts may occur. 

PMID- 12048727
TI  - Cryoextraction in the management of orbital tumors. An old technique revisited.
AB  - Four patients with relatively large orbital tumors are described. These patients
      had superomedial rhabdomyosarcoma, inferomedial cavernous hemangioma, lateral
      primitive neuroectodermal tumor, and superior neurofibroma, respectively.
      Continuing enlargement and encroachment upon vital ocular structures and
      suspicion of malignancy warranted surgical intervention. Following exposure of
      the anterior portions of these tumors, a cryoprobe was used for the complete
      removal of the mass. Cryoextraction greatly facilitates the excision of well
      defined, solid, encapsulated, benign or malignant tumors excluding the lacrimal
      gland and thus minimizes trauma to adjacent tissues. More importantly, the tumor
      can be removed intact without capsular rupture and risk of tumor spill-over or
      hemorrhage. At the histopathological level, the application of a cryoprobe did
      not alter the microscopic structures of the lesions and did not cause any
      difficulty for histopathologic interpretation. 

PMID- 12048728
TI  - Lacrimal diverticula.
AB  - Lacrimal diverticula are outpouchings of the lacrimal drainage system. They are
      suspected clinically by the presence of an intermittent or permanent swelling
      near the lacrimal sac, which can be emptied, by compression, into the lacrimal
      system and by patency on irrigation of this system. A series of 12 cases of
      lacrimal diverticula managed in our department is presented. Five patients
      underwent a simple dacryocystorhinostomy (DCR) with or without intubation, two
      had a DCR and excision of the diverticulum and two had an excision of the
      diverticulum only. All operated cases remained asymptomatic. As diverticula tend
      to become infected, they should be treated by excision of the diverticulum with
      repair of its connection to the lacrimal system. A DCR may be performed in
      addition, but is probably not always necessary. 

PMID- 12048729
TI  - Lacrimal canalicular obstruction in lichen planus.
AB  - PURPOSE: To report, for the first time, proximal canalicular obstruction in all
      four canaliculi of a patient with lichen planus. METHODS: The patient file and
      examination findings were reviewed, along with relevant literature on lichen
      planus and the eye. RESULTS: A 67-year-old woman with lichen planus had bilateral
      epiphora. All four canaliculi were totally obstructed within 2-3 mm of the
      puncta, and there was mild medial subconjunctival scarring. CONCLUSIONS: Lichen
      planus is an immune-mediated skin and mucosal disease similar to pemphigoid and
      lacrimal canalicular obstruction may occur as part of the disease. 

PMID- 12048731
TI  - Cavernous hemangiomas of the orbit (2).

PMID- 12048732
TI  - Cavernous hemangiomas of the orbit (reply to the 2nd letter by Alan A. McNab).

PMID- 12048730
TI  - Orbital inflammation in Churg-Strauss syndrome.
AB  - A 66-year-old woman with Churg-Strauss syndrome (asthma, vasculitis and
      eosinophilia) presented with diffuse orbital inflammation which was treated
      effectively with 50 mg oral prednisolone daily. The orbital inflammation rapidly
      settled and the prednisolone was reduced over a two-week period. Seven years
      earlier, inflammation of the opposite lacrimal gland had also responded rapidly
      to oral prednisone. Although she had asthma at this time, Churg-Strauss syndrome
      was only diagnosed some years later. Patients with Churg-Strauss syndrome may
      present with orbital inflammation in addition to the more common neuro-ophthalmic
      manifestations of vasculitis affecting retina, choroid, optic nerve or ocular
      motor nerves. 

PMID- 12048733
TI  - Searching the literature on cavernous hemangioma of the orbit.

PMID- 12048734
TI  - Humanness, personhood, and the right to die.

PMID- 12048735
TI  - The legal protection of HIV+ health care workers and the human rights
      jurisprudence of the European Court of Justice.

PMID- 12048736
TI  - Bouncing boundaries and breaking boundaries -- the case of assisted-suicide and
      criminal law in Canada.

PMID- 12048737
TI  - Death of the self: changing medical definitions in Japan and the U.S.

PMID- 12048738
TI  - Scientific character of brain death argument and legal justice.

PMID- 12048739
TI  - Beta blocker use in acute myocardial infarction in West Virginia.
AB  - This article describes our study of the use of beta blocker drugs in Medicare
      beneficiaries hospitalized for acute myocardial infarction in West Virginia
      between 1999 and 2000. We contrasted findings with the responses of practicing
      cardiologists in the state. The survey asked cardiologists to describe their
      recent patterns of beta blocker usage, to comment on the severity of generally
      recognized contraindications to beta blocker administration, and to speculate on
      reasons why West Virginia's rates of beta blocker use in AMI were lower than
      rates in most other states. Our study revealed that beta blocker use in AMI
      declined significantly with patient age, and that rates of use in larger
      hospitals exceeded those in smaller hospitals. There was little difference
      attributable to the specialty of the admitting physician. We also observed a
      positive association between the use of beta blockers in AMI and other
      appropriate interventions, such as the use of aspirin and revascularization.
      Cardiologists said they were using more beta blockers in AMI than five years ago,
      and speculated that high rates of chronic obstructive pulmonary disease and non
      specialist physicians were responsible for low rates in West Virginia.

PMID- 12048740
TI  - Hyperandrogenemia associated with insulin resistance mimicking an androgen
      producing tumor.
AB  - The finding of a serum testosterone level greater than 200 ng/dl in a woman with
      virilization raises concerns about an androgen producing tumor. This case report
      demonstrates that chronic annovulation in association with insulin resistance can
      cause significant elevations in the level of serum testosterone, and describes
      the therapeutic benefit of insulin sensitizing agents in reversing
      hyperandrogenemia.

PMID- 12048742
TI  - The need for a statewide pediatric trauma program.
AB  - Development and maintenance of an effective regional trauma care system mandates
      on-going assessment of those at risk, patterns of injury and types of resources
      available. It is known that a significantly higher injury and traumatic death
      rates exists for children in a rural environment, and there is also evidence to
      support improved outcomes for children treated at verified trauma centers. While
      many still rely on practice-based statistics, we postulated that population-based
      statistics are much more reflective as to what is actually happening and provide
      crucial information on how improvements can be achieved. To test this theory, we
      reviewed all pediatric traumatic deaths for children 18 years old and younger
      from Jan. 1, 1990 to Dec. 31, 1998 at the Jon Michael Moore Trauma Center at West
      Virginia University, a rural pediatric trauma center. We compared this data to
      trauma mortality within the center's 13 county primary region from the Office of
      Vital Statistics. Our research revealed that mortality from pediatric trauma is
      higher in rural environments than in urban environments, and that population
      based statistics more accurately reflect the true impact of what is actually
      happening in any given region. Age appears to be an important factor in
      determining which children are transferred to the trauma center and this may
      represent a critical factor in outcome.

PMID- 12048741
TI  - Neuroleptic malignant syndrome associated with risperidone and olanzapine in
      first-episode schizophrenia.
AB  - This case report describes an 18-year-old African American male who presented to
      a state psychiatric facility with symptoms of bizarre behavior, delusions and
      auditory hallucination. He was diagnosed with schizophrenia and treated with
      eight days of risperidone followed by five days of olanzapine. During this two
      week period, this patient began to develop signs and symptoms of neuroleptic
      malignant syndrome (NMS). Two weeks after all neuroleptic medications were
      discontinued, all his vital signs and labs returned to baseline. This case report
      and others from literature suggest that risperidone and olanzapine may induce NMS
      in some patients.

PMID- 12048743
TI  - WVU neurosurgeon uses 3-D images to locate brain tumors.

PMID- 12048744
TI  - Research will help chemotherapy patients avoid memory loss.

PMID- 12048745
TI  - Really dead.

PMID- 12048746
TI  - Rhode Island's first hospitals.

PMID- 12048747
TI  - Older men in Rhode Island, 1995-2025: population, life expectancy, and men's
      health issues.

PMID- 12048748
TI  - The evaluation and treatment of BPH, 2002.

PMID- 12048749
TI  - Male urinary incontinence.

PMID- 12048750
TI  - Osteoporosis and the aging male.

PMID- 12048751
TI  - Borderland.

PMID- 12048752
TI  - Primary and secondary prevention of stroke.

PMID- 12048753
TI  - Cancer incidence in Rhode Island cities and towns, 1987-2000.

PMID- 12048754
TI  - Develop stakeholder relationships with focus groups.
AB  - Because of the current competitive climate for funding and volunteers, health
      care philanthropies are increasingly concerned about cultivating stakeholders.
      Today's focus is on long-term relationships with stakeholders, rather than on
      short-term fund raising. Using focus groups--a discussion about a particular
      topic, involving eight to 12 participants lead by a moderator--is an efficient,
      cost-effective way to cultivate stakeholders.

PMID- 12048755
TI  - "Tell me why you give". A fresh approach to direct mail solicitation that
      produced a huge return.
AB  - Having trouble writing an appear letter? With inspiration from a book on love
      stories, Fletcher made a simple request of his donors and was surprised by the
      response. See how one question generated an incredible return--financially and in
      donor support.

PMID- 12048756
TI  - Lean, mean ... and in-between: corporate language and philanthropy. Promote
      philanthropy with effective language.
AB  - With many of our donors in the corporate world, we often use their corporate
      language when speaking about our institutions. Be careful--a "corporate-only"
      message can undermine the efforts of a development program. Many of your donors
      may be wondering why your institution needs funds if you are the paragon on
      corporate success.

PMID- 12048757
TI  - Being on top and keeping balance.

PMID- 12048758
TI  - Eight steps to HIPAA compliance.

PMID- 12048759
TI  - Physicians and fund development. Part II.  Cultivating donors. Physicians as an
      essential link.
AB  - Physicians have a vested interest in the outcome of philanthropic activities that
      advance programs and services at your institution. This Top 10 list will help you
      discover the project or area that excites a physician's passion and ultimately
      gets them involved in fund development.

PMID- 12048760
TI  - Use data to get surgeons to the OR on time.

PMID- 12048761
TI  - Sharing data with physicians helps break down barriers.
AB  - An aggressive data-sharing effort between managed care administrators and
      physicians at HealthPartners in Minnesota has boosted clinical outcomes and
      enhanced clinical processes.

PMID- 12048763
TI  - Study makes strong case for early diabetes intervention.

PMID- 12048762
TI  - Iowa Health System takes QI statewide.
AB  - Tailoring QI efforts to meet local conditions plays second fiddle at the Iowa
      Health System. Instead, the focus is on consistent, predictable QI methods that
      can be replicated statewide. The strategy is paying off.

PMID- 12048765
TI  - Diverse approaches to asthma DM succeed in Medicaid populations.
AB  - Diverse approaches to asthma CM can produce results in Medicaid populations. It's
      one of the toughest groups to manage, but health care organizations willing to
      reach out to all eligible candidates and target specific barriers to care are
      making solid headway. And, as the experiences of two organizations illustrate,
      there is more than one route to success.

PMID- 12048766
TI  - New approaches to medication compliance look to behavior change theory for help.
AB  - Consider new approaches to medication compliance. Why? Because roughly half of
      all prescriptions are taken incorrectly--if at all--and an estimated 20% aren't
      even filled. Experts say the problem is costing the health care system billions
      per year, and it must clearly be affecting outcomes as well. For these reasons,
      researchers are coming up with new ways to boost medication compliance, including
      the notion of applying behavioral theory to the problem. Check out some new
      solutions that are in the pipeline.

PMID- 12048764
TI  - New, easy-to-implement system for cholesterol management yields outstanding
      results.
AB  - Is there a better way to manage cholesterol? Providers at one large heart center
      think there is, and they have some strong evidence to back them up: Among
      patients tracked over the last two years, a whopping 88% are within 10% of the
      goal recommended by national guidelines. The best news, however, is that this new
      system for managing cholesterol is quick, easy, and providers have readily
      embraced it.

PMID- 12048767
TI  - Prostate cancer options expand beyond the PSA.

PMID- 12048768
TI  - New CHF drug shown to ease breathing distress among hospitalized patients.
AB  - Natrecor (nesiritide) is targeted to acute decompensating CHF patients.

PMID- 12048769
TI  - Disease-specific drug education programs hit their target.

PMID- 12048770
TI  - Precribing feedback, 'cue cards' improve management of high-risk seniors.

PMID- 12048771
TI  - St. Louis system finds success with tailor-made QI efforts.
AB  - SSM Health Care's systemwide initiative to encourage voluntary, local innovation
      in quality improvement is reflecting on what worked, and what to do as the next
      phase begins.

PMID- 12048772
TI  - [Technology for forming a single-row subampular and suprasphincter colorectal
      anastomosis].

PMID- 12048773
TI  - [Trauma to the right diaphragmatic cupola with transposition of a lobe of the
      liver into the pleural cavity, complicating perforated duodenal ulcer].

PMID- 12048774
TI  - [Ectopic varications in cavernous transformation of the portal vein].

PMID- 12048775
TI  - [Use of domestic vascular prosthesis from polytetrafluoroethylene "Ekoflon" in
      surgery for aneurysm of the thoracic aorta].

PMID- 12048777
TI  - [Surgical treatment of post-traumatic aortovenous fistula].

PMID- 12048776
TI  - [Results of using the domestic vascular prosthesis "Ekoflon"].
AB  - The aim of the work was to study long-term results of application of a vascular
      transplant from modified polytetrafluoroethylene "Ekoflon". The investigation
      included 121 reconstructions performed during the last 6 year, 53 prostheses
      being implanted in the aorto-femoral position, 68--in the femoro-popliteal-tibial
      position. The long-term results have shown that the transplant "Ekoflon" in the
      position of the aorto-femoral shunt is not inferior to textile analogues and even
      has a number of advantages. When it is used below the inguinal fold the results
      of patency were worse than those with the autovenous one. But when there is no
      adequate autovein, under conditions of critical ischemia, prosthesis "Ekoflon"
      might be the material of choice for saving the lower extremity. The dynamic
      ultrasound duplex scanning and histological investigation of the prosthesis
      samples have shown an original morphogenesis of its "implantation".

PMID- 12048778
TI  - [Modern problems in treating rectal cancer. Part I].

PMID- 12048779
TI  - [Search for a sentinel lymph node--way to optimize lymphodissection in neoplasms
      of various locations].

PMID- 12048780
TI  - [Features of forming oxidative stress in blood of postinfarct cardiosclerosis
      patients during aortocoronary bypass].
AB  - Patients with postinfarction cardiosclerosis in association with angina (NYHA
      class III) during coronary artery bypass grafting usually develop oxidative
      stress in erythrocytes which is characterized by enhanced free radical oxidation
      and depression of antioxidative enzymes. This process is of especially great
      importance and lasts longer in patients with the reperfusion syndrome. The
      consequences of this process could be revealed as derangement of the functional
      and structural state of erythrocytes, "rheological crises", further depression of
      the postischemic myocardium, rhythm and coronary flow disturbances. The results
      obtained show the effective prophylactics and antioxidant treatment of the
      oxidative stress syndrome to be necessary.

PMID- 12048781
TI  - [Change in lymphatic circulation of lower extremities and prospects for
      lymphotrophic therapy in trophic ulcers of venous etiology].
AB  - Investigations of the lymphatic bed of lower extremities by the method of rentgen
      contrast lymphography were performed in 64 patients with trophic ulcers of lower
      extremities and postthrombotic disease. The data obtained by lymphography allowed
      formation of a group of patients perspective for treatment by lymphotropic
      antibacterial therapy. The lymphotropic therapy using Gentamycin and Cefazolin
      resulted in a more rapid arresting of local inflammatory alterations and
      development of reparative processes in the trophic ulcer area and in
      normalization of the main clinico-laboratory parameters.

PMID- 12048782
TI  - [Associated post-gastric resection syndromes].
AB  - In the clinic there were 545 patients treated for postgastroresectional
      syndromes, 289 (53%) of them had associated postgastroresectional syndromes. A
      mild degree of clinical manifestations of the associated syndromes was found in
      11%; medium degree in 35% and severe--in 54% of the patients. An individualized
      approach to the decision for methods of reconstructive operations was
      substantiated which allowed to get positive results in 95% of the patients.
      Postoperative lethality was 1.8%.

PMID- 12048783
TI  - [Experience in treating patients with postvagotomy syndromes].
AB  - The article generalizes experiences with treatment of 257 patients with
      postvagotomy syndromes (PVS). The patients were distributed according to the
      character of the syndromes. Main causes of the development of PVS are discussed.
      The authors describe the specific methods of diagnosis allowing individualized
      approach to option of the program of treatment. Criteria of decision in favor of
      various methods of reconstructive-restorative procedures are proposed. The
      individualized approach to treatment allowed to get considerably better condition
      in 95% of patients with PVS.

PMID- 12048784
TI  - [Differential surgical treatment of idiopathic megadolichocolon in adults].
AB  - An analysis of results of surgical treatment of 158 adult patients with the
      syndrome of chronic colostasis (SCC) has shown that the rectal form of
      Hirschsprung's disease (RFH) was diagnosed in 57 patients while idiopathic
      megadolichocolon (IMC)--in 101 patients. There were two types of SCC: proctogenic
      and cologenic. The proctogenic type appears in patients with RFH due to
      hypogangliosis and agangliosis, and in patients with IMC--as a result of
      dystrophy of ganglionic neurons of the Meissner plexus of the rectum. The
      computed morphometry and histochemical investigations have shown that
      hypogangliosis and agangliosis in RFH were of congenital origin while dystrophy
      of the rectal ganglia in many patients with IMC was an acquired pathology. The
      marginal variant of the second type of the colon structure can be considered as a
      cause of SCC. A new operation--endofascial resection of the rectum--is proposed
      for treatment of proctogenic SCC. The differential surgical strategy with
      pathomorphogenesis of SCC taken into account allowed to get satisfactory results
      in 73% of cases.

PMID- 12048785
TI  - [Formation of a colonic reservoir while performing a low anterior resection of
      the rectum].
AB  - The aim of the investigation was to determine the most functionally grounded
      level of the formation of colonic reservoir from the margin of the anal canal
      while performing a low anterior resection of the rectum. Sphincter-preserving
      operations were performed in 113 patient with the formation of colonic reservoir
      and direct stepler colorectal anastomosis. Questionnaires and apparatus
      "Colodynamic-3" were used to follow-up 28 patients with the reservoir (main
      group) and 19 patients with a direct anastomosis on whom the operations had been
      made more than a year ago. The rate of the development of complications was
      almost the same in the both groups--28.5% and 26% correspondingly. The reservoir
      accumulating function became less in the group of "direct" anastomoses. The best
      parameters of the reservoir-accumulating and evacuatory ability of the colonic
      reservoir were found to be in patients with the level of anastomoses 4-6 cm from
      the anal canal margin. Creation of the reservoir was more difficult in patients
      with the carneus mesentery and a small width of the sigmoid colon.

PMID- 12048786
TI  - [A method of surgical treatment of "difficult" inguinal hernias].
AB  - A comparison has been made between the results of 167 hernioplasties performed by
      generally accepted methods (those by Martynov, Girards, Bassini, Sholdis,
      Postemsky) and by the method of deep inguinal hernioplasty developed in the
      clinic for "difficult" hernias. The proposed method eliminates the main
      shortcoming of M.I. Kukudzhanov's method--tension of the sutured tissues. After
      hernioplasty of "difficult" hernias (106 operations) recurrences made up 1.9%.

PMID- 12048787
TI  - [Clinical forms of cholangiogenic infection in surgical practice].
AB  - The acute cholangiogenic infection may have a favorable course or acquire a
      purulent or septic form. Chronic cholangiogenic infection often having
      subclinical features is sometimes septic and is responsible for the transition of
      bacterial cholangitis from the complication to the independent disease. Of
      greatest significance are septic forms of cholangiogenic infection because of
      high lethality. The diagnosis and treatment of cholangiogenic infection include
      the determination of the character of bile duct obstruction, state of immunity,
      character of microflora and kind of toxemia.

PMID- 12048788
TI  - [Surgical treatment of stage III-IV ovarian cancer].
AB  - A residual tumor after primary cytoreductive surgery is one of the most important
      factors of survival of patient with advanced ovarian cancer. Maximal
      cytoreduction can be achieved by different ways. We studied results of extended,
      combined and standard operations on patients treated in the Russian Cancer
      Research Center of the Russian Academy of Medical Sciences in 1989-1999. It was
      found that only optimal cytoreduction resulted in the absence of recurrences and
      better overall survival of the patients independent of the operation type
      (extended, combined or standard).

PMID- 12048789
TI  - [Oxygen tension in would tissues during healing].
AB  - Transcutaneous strain of oxygen (TcPO2) was studied in tissues of 111 wounds in
      110 patients. The uncomplicated course of the wound process was characterized by
      rapid normalization of the initially decreased TcPO2 in the wounds closed with
      sutures or in case of gradual approximation of their margins as well as by a slow
      elevation when the wounds were healing by second intention. High significance of
      measuring TcPO2 was shown for diagnosis of acute pyo-inflammatory diseases and
      wound complications. Great feed-back correlation was found between the degree of
      disjunction of the wound margins and TcPO2 of its tissues. A hypothesis is put
      forward on the dependence between the degree of tissue tension and the
      precapillary sphincter tone allowing an explanation of all the changes in TcPO2
      of the wound tissues in the process of its healing.

PMID- 12048790
TI  - [Complications high frequency catheter destruction of heart conduction pathways].
AB  - An analysis of 490 operations in 442 patients with different variants of
      supraventricular and ventricular tachycardia was made. Complications developed in
      23 cases (4.7%). The least (0.8%) risk of complications was noted in patients
      after destruction of the atrioventricular junction, the greatest (9.6%) in
      patients with abnormal junctions. Measures of treatment depended on the degree
      and severity of the complication and the character of concomitant disease. The
      division of complications into biogenic and technogenic allows the possible
      factors influencing their development to be differentiated. The frequency of
      complications is determined by complexity of the methods used and the necessary
      experience on the one hand, and by the severity of the patient's state and
      coexistent diseases on the other hand.

PMID- 12048791
TI  - [Functional status of the intima and thrombocytic hemostasis in patients with
      symptoms of atherosclerosis of the cerebral and peripheral vessels].
AB  - The indices characterizing the state of lipid metabolism, endothelium of arteries
      and thrombocytic hemostasis were investigated. It was shown that in the zone of
      atherosclerotic stenosis of the arteries there were marked transformations of the
      endothelium followed by a decrease of their anticoagulatory properties. The cause
      and effect relationship between the disturbed thrombocytic hemostasis and lesions
      of the endothelium in atherosclerosis was confirmed. It is these factors which
      are the cause of frequent thromboembolic complications, especially in patients
      with lesions of the cerebral arteries. It is necessary to include methods of
      correction of the disturbed thrombocytic hemostasis in the complex treatment of
      patients with atherosclerosis.

PMID- 12048792
TI  - [Rheography of extracorporeal circulation: verification of method and calibration
      of the monitor].
AB  - Cardiopulmonary bypass as a reference flow model for impedance cardiography
      monitoring is described in 34 children during open-heart surgery. Such an
      approach not only proved the accuracy and precision of impedance cardiac output
      measurement, but also gave a possibility to make intra-operative calibration of
      any cardiac output monitor which maintains its accuracy during the post-bypass
      period.

PMID- 12048793
TI  - [Experimental-clinical basis for using sporobacterin in the combined treatment of
      pancreonecrosis].
AB  - Experimental investigations on translocation of the intestinal microflora on the
      model of acute pancreatitis were performed in 54 animals (albino rats) and showed
      an increased bacterial dissemination of parenchymatous organs of the abdominal
      cavity as the inflammatory and destructive alterations increased in the pancreas.
      E. coli aggravated the inflammatory alterations in the pancreas while B. subtilis
      promoted reparative processes. Experimental substantiation is given to using
      sporobacterin in the complex postoperative treatment of patients with
      pancreatonecrosis.

PMID- 12048794
TI  - [Effectiveness of endovideosurgical technology in diagnosis and treatment of
      patient with hemoblastoses].
AB  - Results of using endovideosurgical technology for diagnosis and treatment of
      hematological diseases in 123 patients are described. It was shown that
      laparoscopy is highly effective parallel with ultrasound examination and
      tomography in a complex diagnostic program. Using the developed diagnostic
      algorithm was shown to be very expedient for making primary diagnosis, recurrent
      diseases and control of the effectiveness of chemotherapy. Endovideosurgical
      interventions were shown to be less invasive and safe in hematological patients.
      Laparoscopy is an alternative to diagnostic laparotomy which is often used in
      this group of patients.

PMID- 12048795
TI  - [Surgical treatment in chronic gastroduodenal ulcers].
AB  - Operative treatment was carried out in 1197 patients with chronic gastroduodenal
      ulcers. Among the most frequent complications of the ulcers there were
      penetration of the III-IV degree, compensated, subcompensated and decompensated
      pyloroduodenal stenosis. The operative interventions included Billroth-II
      resections of the stomach in modification of Hofmeister-Finsterer, Billroth-I,
      with saving the pyloric sphincter, after Roux and gastrectomies. Postoperative
      complications developed in 127 (10.6%) patients, postoperative lethality was
      0.7%. Excellent and good long-term results were noted in 846 (94.5%) patients, in
      14 (1.6%) patients they were estimated as satisfactory and in 35 (3.9%) as
      unsatisfactory. The causes of unsatisfactory results were recurrent ulcers
      (0.7%), peptic ulcer of the gastroenteroanastomosis (0.6%), dumping-syndrome of a
      severe and medium degree (1.5%), diarrhea of a severe degree (0.3%) and erosive
      ulcerous reflux-esophagitis (0.3%).

PMID- 12048796
TI  - [Associated laparoscopic interventions for gallstones].
AB  - Since 1994 till 2000 the authors have performed 1152 laparoscopic
      cholecystectomies. Coexistent diseases of the organs of the abdominal cavity were
      diagnosed in 13.02% of the patients operated on by using laparoscopic techniques.
      In parallel the simultaneous interventions were performed for hiatal hernias,
      ulcer of the duodenum, commissural disease of the peritoneum, chronic duodenal
      obstruction, ventral hernias, diseases of the genital organs, liver and chronic
      appendicitis. The greater volume of the operations when performing the associated
      operations by the laparoscopic method does not make the course of the
      postoperative period more severe and gives good results in 89.3% of the patients.

PMID- 12048797
TI  - [Some pathogenetic aspects of developing liver failure and preventing it in
      patients with liver cirrhosis after portosystemic shunting].
AB  - Patients with cirrhosis of the liver were found to have a considerable
      suppression of the system of biotransformation of the liver before operation
      which correlated with the data of the direct indices of monooxigenase system of
      hepatocytes--cytochrome P-450 and activity of N-demethylase of amidopyrine.
      Operative interventions on such patients independent of the type of portosystemic
      shunting result in considerably decreased content of metabolites of amidopyrine-
      4AAP and N-ac-4-APP in urine as compared with the preoperative level (p < 0.05).
      Hyperbaric oxygenation is the optimal stimulator of activity of the liver
      biotransformation system. Better indicators characterizing the increased
      metabolic activity of the liver were noted in patients with selective
      portosystemic anastomoses and hyperbaric oxygenation in the postoperative period.

PMID- 12048798
TI  - [Antonin Nikolaevich Filatov (1902-1974)].

PMID- 12048799
TI  - [Transcatheter embolization of ovarian vein varicosities].
AB  - Selective retrograde venography and steel coil embolization were performed in 9
      women with the left (n = 7) or bilateral (n = 2) ovarian vein varicosities.
      Within one-three months after the procedure 8 patients showed disappearance or
      decrease of their pain, dysmenorrhea, and other symptoms of pelvic congestion.
      These favorable effects of treatment retained during 2 to 7.5 years of follow-up.
      It was concluded that the transcatheter embolization is safe and effective for
      treatment of the symptomatic ovarian varicosities. The advantages of this method
      include the possibility to perform the procedure in the outpatient conditions,
      low risk of the appearance of side effects and complications, excellent cosmetic
      results which makes the embolization a preferable alternative to surgical or
      laparoscopic ligation.

PMID- 12048800
TI  - [Meaning of the "final operation" in the Zollinger-Ellison syndrome].
AB  - Under analysis there were data of 37 patients with the Zollinger-Ellison syndrome
      (ZES), 36 of them were operated upon. Gastrinomas were found in 21 patients, in 7
      of them they were undoubtedly malignant. No tumors were found during operation in
      15 patients operated upon with obvious clinical picture of ZES. Treatment of
      patients with ZES must be differentiated, the patients must be divided into
      several groups. The idea of "final operation" is substantiated. It can include
      enucleation of gastrinoma, resection of the pancreas, truncal vagotomy with
      antrumectomy and sometimes a removal of the stomach or its stump if there had
      been a resection of the stomach, i.e. a removal of the "target-organ". The
      necessary succession of medical measures and choice of the operation volume are
      substantiated in the two given schemes of algorithms with explanations on the
      basis of personal experiences with treatment of 37 patients with ZES.

PMID- 12048801
TI  - [Rational method of surgical treatment in nephroptosis].
AB  - The article is devoted to surgical treatment of patients with nephroptosis. New
      and rational methods of nephropexy are described such as subcapsular along the
      posterior surface of the lower pole, by paranephral fatty tissue of the lower
      pole and by the fatty tissue with conducting the muscle flap through it. The data
      concerned with the number and results of the operations performed are given, the
      differential approach to using the methods in question being formulated.

PMID- 12048802
TI  - [Comparison of parameter optimization algorithms for environmental model].
AB  - Parameters identification is achieved through the minimization of objective
      function based on model outputs and the observed data. Because of ever increasing
      complexity of environmental-models, there are significant difficulty for
      conventional optimal methods to present a global optimization. On the contrast,
      however, direct optimization algorithms are widely developed in recent years due
      to increasing computer efficiency and show promising applications. Four direct
      optimal algorithms, i.e. CRS algorithm, SCE UA algorithm, SA algorithm and
      Annealing-Simplex algorithm, were thus selected in this paper to compare their
      performances via case studies.

PMID- 12048804
TI  - [Characteristics of forms of fluorine in soils and influential factors].
AB  - Forms of fluorine in 15 different soils were studied using sequential chemical
      extraction procedure. The fluoride forms in soils were separated into five
      fractions: water soluble fluoride (Ws-F), exchangeable fluoride (Ex-F), fluoride
      bound to Fe/Mn oxides (Fe/Mn-F), bound to organic matter (Or-F), and residual
      fluoride (Residual-F). The contents of different fluoride forms were decreased in
      the order: Residual-F >> Ex-F > Ws-F > Or-F > AoFe-F. Correlation analyses showed
      that Ws-F was significantly correlated with Ex-F (r = 0.775* *). Ex-F was
      correlated with Fe/Mn-F (r = 0.5753*) and Organic-F (r = 0.5529*). Stepwise
      linear regression analysis was used to test the effect of various soil components
      on the contribution of fluoride forms, indicating that soil pH, organic matter,
      clay content, and exchangeable calcium content were the important influential
      factors and pH was the most important influential factor. In addition, soil
      parent materials had also influence on forms of fluorine.

PMID- 12048803
TI  - [Desorption of kaolin adsorbed copper in the fish gill microenvironment].
AB  - In order to investigate the bioavailability of kaolin adsorbed copper on gills of
      carpio, and to explain its possible mechanism in terms of speciation, exposure
      experiments with constant concentration of water soluble copper and increased
      concentration of kaolin adsorbed copper was carried on, and the speciation
      analyses was developed using MINTEQA2. The results of the exposure experiment
      indicated that expose to kaolin adsorbed copper would increase the metal
      accumulation in the fish gills. The shift of the copper speciation was
      demonstrated via chemical equilibrium calculation. To be specific, the kaolin
      adsorbed copper would be partially desorbed in the fish gill microenvironment in
      the alkaline water environment.

PMID- 12048805
TI  - [Intermediate experiment and mechanism analysis of flue gas desulfurization
      technology by circulating fluidized bed].
AB  - A new Circulating Fluidized Bed was designed for intermediate experiment of flue
      gas desulphurization, in which the flue gas flow rate was 3500 m3/h. By using it,
      the basic experiments were carried out to study the influence of Ca/S and
      supersaturated temperature on desulphurization efficiency and the effect of the
      recycling solid particle in the sulfur removal column on desulphurization
      performance. The results showed when Ca/S = 1.2, the desulphurization efficiency
      was increased by 15% through the recycle of solid particle; the gas velocity
      inside the bed could be designed higher. The mechanism analysis were also studied
      and the method to increase effective resident time was introduced.

PMID- 12048806
TI  - [Recovery process of nitric acid, copper and nickel in deplating wastewater].
AB  - The recovery process of nitric acid, copper and nickel in deplating wastewater
      was developed by using the combined technique of distillation, solvent extraction
      and precipitation. The conditions of the separation of copper and nickel by
      solvent extraction using P507 in kerosene and stripping copper with H2SO4 were
      specially investigated and the optimal parameters were determined. The results of
      experiment indicated that the recovery ratio of nitric acid was 97.8%, and under
      the optimized conditions of extraction process, concentration of original
      effluence ranged in 15-20 mg/mL copper, 5-10 mg/mL nickel, pH 1-2, concentration
      of extractant was 35% (V/V), saponification degree was 60%, phase ratio was 1:1,
      reaction time was 2 min, temperature ranged in 20 degrees C-25 degrees C, the one
      stage extraction efficiency of copper was higher than 90%, the separation ratio
      of copper and nickel was up to 75; copper and nickel could be completely
      separated by a continuous countercurrent three-stage extraction. The nickel could
      be recovered from the water phase by precipitating with NaOH and the recovery
      ratio of nickel reached up to 99.9% by controlling pH in solution within 10-11.
      After these treatment, the effluent could meet the national standards of
      wastewater discharge.

PMID- 12048807
TI  - [Species dynamic change of added Rare Earth element in soil].
AB  - After Rare Earth elements (REEs) was applied into soil, content of exchangeable
      species decreased obviously with time lapsing. The fastest decrease of content of
      exchangeable species occurred at wheat tillering stage. A part of the lost
      content of exchangeable species was absorbed by wheat, and the other part of that
      was absorbed by soil. The surface activity of iron/manganese oxide was influenced
      obviously by the secretion function of root, content of iron/manganese oxide
      binding species rapidly increased before wheat jointing stage, but it decreased
      quickly after wheat jointing stage. At all time, content of carbonate binding
      species decreased with time lapsing, and content of residual species and content
      of organic binding species didn't change.

PMID- 12048808
TI  - [The effect of the dosage of TiO2 and its surface-loaded silver on the
      photocatalytic degradation of aroclor1260].
AB  - The dosage of TiO2 and its surface-loaded silver had notable effect on the
      photocatalytic degradation of Aroclor1260, under ultraviolet light. The dosage of
      TiO2 had no proportion to the degradation rate of Aroclor1260, but had an optimal
      value, which was 3 g/L under the experimental condition. The degradation rate of
      Aroclor1260 increased with the increasing of loading silver, and the PCBs
      congeners with higher concentration had higher degradation rate. The catalytic
      activity of TiO2 increased with the amount of loading silver increasing.

PMID- 12048809
TI  - [Detection of the strong mutagen MX in drinking water].
AB  - MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] was found to be the
      most potent mutagen in chlorinated drinking water. MX in some tap waters in
      Jiangsu Province was absorbed by XAD-8 resin, methylized with saturated BF3-CH3OH
      and detected using GC/MS. The contents of MX in the tap waters were between 0.58
      to 20.0 ng.L-1, except one of those samples. More MX was produced in low-water
      season.

PMID- 12048810
TI  - [Experimental investigation on sulfur emission properties of micro-pulverized
      coal].
AB  - Micro-pulverized coal(0-20 microns) combustion is a new kind of pulverized coal
      combustion technology. Four Heshan sulfur coal samples with different mean
      particles diameter were combusted, using a TGA-FTIR made in Germany. Micro
      pulverized coal self-desulfurization and adding CaO desulfurization
      characteristics were investigated. Experimental result proved that micro
      pulverized coal SO2 emission was less than coarse particles, and with the same
      Ca/S molar ratio 3 micro-pulverized coal can obtain higher sulfur capture
      efficiency. Its unique desulfurization property provide a new idea path for
      reduce sulfur releasing from pulverized coal combustion.

PMID- 12048811
TI  - [Calculating of critical loads of sulfur deposition for surface waters in
      southern China using a steady-state acidification model].
AB  - In order to study the response of Chinese surface waters to acid deposition, a
      steady-state model based on acidity balance was applied in this paper to
      calculate critical loads of sulphur deposition for surface waters in southern
      China. An empirical equation for Chinese surface waters was obtained to calculate
      the background sulfate concentration. The results showed that the critical loads
      of sulphur deposition for most surface waters in southern China were more than
      2.0 keq.(hm2.a)-1, indicating that they were not sensitive to acidification.
      Surface waters with critical loads less than 2.0 keq.(hm2.a)-1 were those waters
      located on mountains. Except these mountain waters, the critical loads of sulphur
      deposition for other surface waters were not exceeded by the present sulphur
      deposition, indicating acidification will not occur in the near future for these
      waters. The spatial distribution of critical load exceedance was similar with
      that of the critical loads, showing the trend of increasing from the southeastern
      provinces, such as Fujian, Guangdong and Jiangxi, to the southwestern and the
      central region. The uncertainty analysis of the model results indicated that, the
      errors of the results caused by the uncertainty of parameters and the input data
      were minor and acceptable so long as the input data were among the appropriate
      ranges.

PMID- 12048812
TI  - [Predicting low NOx combustion property of a coal-fired boiler].
AB  - More attention was paid to the low NOx combustion property of the high capacity
      tangential firing boiler, but the NOx emission and unburned carbon content in fly
      ash of coal burned boiler were complicated, they were affected by many factors,
      such as coal character, boiler's load, air distribution, boiler style, burner
      style, furnace temperature, excess air ratio, pulverized coal fineness and the
      uniformity of the air and coal distribution, etc. In this paper, the NOx emission
      property and unburned carbon content in fly ash of a 600 MW utility tangentially
      firing coal burned boiler was experimentally investigated, and taking advantage
      of the nonlinear dynamics characteristics and self-learning characteristics of
      artificial neural network, an artificial neural network model on low NOx
      combustion property of the high capacity boiler was developed and verified. The
      results illustrated that such a model can predicate the NOx emission
      concentration and unburned carbon content under various operating conditions, if
      combined with the optimization algorithm, the operator can find the best
      operation condition of the low NOx combustion.

PMID- 12048813
TI  - [The conversion from CS2 to COS by spark discharge].
AB  - Spark discharge method was used to take simulative investigations on the
      conversion reaction from CS2 to COS by lightning. The results showed that 1.33 x
      10(3) Pa CS2 could act with O2 or H2O in the atmosphere (25 degrees C, 10(5) Pa)
      under electric discharge conditions (V = 3000 V), and COS was produced as well as
      other species such as CO, CO2, SO2 and so on. Factors such as CS2 concentration,
      water vapor and discharge time played important roles in the formation of COS.
      Based on these results and several theories, possible mechanisms of correlative
      processes during thunderstorms were proposed here, which could contribute to give
      evidence for the conversion from CS2 to COS by lightning during thunderstorms.

PMID- 12048814
TI  - [Dechlorination of chlorinated ethenes under different redox conditions].
AB  - Chlorinated ethenes are pollutants in contaminated soil and groundwater, and one
      of the efficient way to remove them is biodegradation. In this paper, the
      microbial breakdown of PCE, cis-DCE and VC with initial concentrations of 100
      mumol/L were studied under different redox conditions at temperature 20 degrees
      C. The results showed that in the presence of ferric iron and carbon dioxide, PCE
      were dechlorinated to TCE (0.26/day) and cis-DCE (0.31/day), respectively. In the
      presence of fatty acids and without competition from inorganic electron
      acceptors, all the studied chlorinated compounds were completely dechlorinated to
      ethenes. However, the degradation rates of cis-DCE and VC (0.04/day) were much
      lower than that of PCE (0.57/day). Under denitrifying, manganese reducing and
      sulfate reducing conditions, no degradation of chloroethenes was observed. When
      the temperature was lowered to 12 degrees C, the activities of dechlorinating
      microbes were also reduced, nevertheless, the completely reductive dechlorination
      of chloroethenes still occurred.

PMID- 12048815
TI  - [The ecological succession of climax community restricted by COD/SO4(2-) ratio in
      acidogenic desulfate bioreactor].
AB  - The ecological succession of climax community restricted by COD/SO4(2-) ratio,
      the causing ecological factors, was investigated in acidogenic desulfate
      bioreactor with continuous-flow and batch-flow experiment. It was demonstrated
      that acetic acid type metabolization and acetic acid type climax community were
      the typical characteristic of acidogenic desulfate ecosystem, and the internal
      balance and feedback adjusting mechanism of the climax community was analyzed. In
      addition, three dimension realized ecological niche figure of preponderant
      population during the course of ecological succession was presented based on the
      following ecological factors of pH value, oxidation reduction potential and
      alkalinity.

PMID- 12048816
TI  - [The application of nanofiltration membrane in the concentration and separation
      of lincomycin wastewater].
AB  - Two spiral nanofiltration membranes, MPS-44 (1.4 m2) and DLNF2-30 (0.24 m2), were
      connected in series to test the concentration process of lincomycin wastewater.
      Results indicated when the water inflow concentration was about 200 mg/L, the
      lincomycin concentration can reach 2000 mg/L after being concentrated for about
      10-20 times. Such concentration can reach the demand of reuse, and the
      concentrating time was 60-70 h. During the concentration process, the CODCr
      retention was always above 80%, and the lincomycin retention was always over 90%,
      and the lincomycin recycle rate was over 90%.

PMID- 12048817
TI  - [Membrane filtration characteristics and its influencing factors in coagulation
      microfiltration combination process for water purification].
AB  - A coagulation-microfiltration combination process was used to treat micro
      polluted raw water in the intermittent operation mode. The effect of the
      operational parameters such as filtration time and aeration intensity, on the
      membrane filtration characteristics was investigated. An indicator J/p, defined
      as flux per unit pressure, was employed. At all the experimental conditions, J/p
      always fell down fast at first owing to membrane fouling, and then decreased
      slowly. But the initial decreasing rate and relative stable value of J/p in the
      latter period depended on the different operational parameters. J/p was greatly
      influenced by the filtration time, then the ratio of the filtration time to the
      ceasing time. Under the condition the filtration time was shortened by 1/2, the
      flux will increase by two times; when the ratio of filtration time/ceasing time
      was shortened, the flux was increased by only 50%. Higher J/p value could be
      achieved at the filtration time of 15 min and the ratio of filtration
      time/ceasing time of 3.8. Increased aeration intensity could enhance J/p to some
      extent. In the experiments, when the aeration intensity was increased from 2 to 4
      m3/h, the membrane permeability was increased by about 15%; and the membrane
      permeability would not increased if the aeration intensity was continuously
      increased to 6 m3/h. Primary inorganic elements on the membrane surface at the
      present experimental condition were found to be Si and Ca from the element
      analysis.

PMID- 12048818
TI  - [Using a two-stage SBR process for removal of organics and nitrification
      denitrification via nitrite].
AB  - High efficiency removal of organics and nitrogen by using a two-stage SBR process
      was introduced in this paper. Most of organics was removed in the first stage SBR
      reactor(SBR1) under the aerobic condition. Subsequently the second stage SBR
      reactor(SBR2) firstly operated under the aerabic condition for simultaneous
      nitrification and removal of a small amount of residual organics. Nitrification
      was controlled to the nitrite-type nitrification. Then denitrification happened
      in SBR2 under the anoxic condition. The petrochemical industry wastewater was
      used as external carbon sources in the denitrification. The experimental results
      indicated that in a two-stage SBR system, two kinds of biomass with the different
      function existed in the different reactors, which was beneficial to improve the
      treatment efficiency. The effluent COD reduced again because SBR2 removed COD
      which was left in SBR1 effluent. It resisted the disturbance of the high organic
      loading to nitrification. Consequently, as compared to a single SBR process, a
      two-stage SBR not only improved the treatment efficiency, but also saved the
      energy cost.

PMID- 12048819
TI  - [Structural properties of TiO2 thin film modified by carbon black].
AB  - TiO2 photocatalytic film(CB-TiO2) modified by doping carbon black was prepared,
      and the some structural properties, such as specific surface area, phase, crystal
      grain size and excitation wavelength were gave, through liquid nitrogen
      adsorption, X-ray diffraction(XRD) and diffuse reflection spectrum(DRS). The
      results indicated that adsorbability of CB-TiO2 was greatly improved, BET
      specific surface area of which enhanced 50%-80% than that of TiO2, baked under
      300 degrees C-500 degrees C. And CB modification reduced the crystal grain size,
      so the temperature of phase transformation was decreased. Corresponding, the
      photocatalytic activity of CB-TiO2 also was greatly improved, the reaction rate
      of which was 1.5 times of that of TiO2.

PMID- 12048820
TI  - [Mechanisms of separating lignin from black liquid by inorganic microfiltration].
AB  - The effects of rejection to lignin from black liquid were carried out by
      inorganic membranes which had pore size 50 nm, 0.2 micron and 0.8 micron,
      respectively. The results show that MF membranes can effectively separate lignin
      from black liquid. The flux of 0.2 micron alpha-Al2O3 and ZrO2 membranes were
      larger than the flux of 50 nm and 0.8 micron membranes. The flux of each membrane
      drops deeply as the SS concentration increased under the conditions of low SS in
      black liquid. However, the flux dropping had the linear relationship with SS
      concentration when it was high. 2 g/L polyethylene glycol 4000 solution can not
      affect the fluxes of 0.2 micron and 50 nm membranes, effectively, instead of
      decreasing the flux of 0.8 micron membrane about 60%. 2 g/L polyethylene glycol
      20,000 solution can sharply decrease the flux of each membrane. Reason that
      provoke flux decreasing and change the rejective ability was the cake formation
      on the surface membrane and the lignin aggregation.

PMID- 12048821
TI  - [Diffusion coefficients of ammonia, nitrate and nitrite in cell-free and cell
      containing PVA gel membranes].
AB  - The cell-free PVA gel membrane and cell-containing PVA gel membrane were prepared
      by iterative freezing and thawing, and the diffusion coefficients of ammonia,
      nitrate and nitrite in PVA gel membranes were determined. The effect of the
      conditions of preparing PVA gel membranes and cell concentration on the diffusion
      coefficients of ammonia in PVA gel membranes were investigated. The results shown
      the diffusion coefficients of ammonia in PVA gel membranes decreased while the
      iteration times of freezing-thawing or PVA concentration or cell concentration
      increased. The diffusion coefficients of ammonia, nitrate and nitrite in cell
      free PVA gel membranes (PVA concentration was 15%) were 0.69 x 10(-9) m2/s, 0.52
      x 10(-9) m2/s, and 0.56 x 10(-9) m2/s, respectively. The diffusion coefficients
      of ammonia, nitrate and nitrite in cell-containing PVA gel membranes (the cell
      concentration was 60 g/L) were 0.55 x 10(-9) m2/s, 0.46 x 10(-9) m2/s, and 0.45 x
      10(-9) m2/s, respectively.

PMID- 12048823
TI  - [Estimating critical loads of sulfur and nitrogen for Chinese soils by steady
      state method].
AB  - Supported by the geographical information system (GIS), critical loads of sulfur
      and nitrogen of Chinese soils were estimated through the steady state method.
      Results showed that the lowest critical loads of sulfur [< 0.3 g.(m2.a)-1]
      occurred on the Daxingan Mountain, Xiaoxingan Mountain and Changbai Mountain in
      northeast China, the valley of the Yaluzangbu River on the south of the Tibetan
      Plateau, and the catchments of the Nu River and the Lancang River in the
      southwest of Yunan province. However, the critical loads of southeast China,
      where acid deposition was very high, were intermediate and in the range of 0.8
      3.2 g.(m2.a)-1. According to the critical loads of sulfur, China might be divide
      into two parts approximately by the 400 mm isohyet-the northwest part could
      generally tolerate more than 3.2 g.(m2.a)-1 sulfur deposition, but the southeast
      one could not. Dislike the distribution of the critical loads of sulfur, the
      critical loads of nitrogen were low in the west China and high in the east. The
      lowest critical loads of nitrogen [< 1.0 g.(m2.a)-1] occurred on the west of the
      Tibetan Plateau and on the Alashan Plateau, and the highest [> 4.0 g.(m2.a)-1] on
      the Dongbei Plain, the Huabei Plain, the Changjiangzhongxiayou Plain, and the
      Sichuan Basin, etc.

PMID- 12048822
TI  - [Effects of polyacrylamide on settling and separation of oil droplets in polymer
      flooding produced water].
AB  - The research found anion polyacrylamide (HPAM) had positive and negative effects
      on oil-water separation. Polymer made oily wastewater's viscosity increase and
      reduce rising velocity, and polymer can also increase intensity of water films
      between oil droplets and lengthen coalescence time of oil droplets. Those were
      not in favor of settling and separation for oil droplets. The positive effects on
      separation were that polyacrylamide had flocculating activity and made small
      droplets contact each other and combine into big droplets. When polymer's
      molecular weight was 2.72 x 10(6), and concentration was less than 800 mg/L,
      polymer was in favor of oil droplets settling and separation. The prime reason
      for oily wastewater of polymer flooding difficult to dispose was that initial
      median diameters of oil droplets were small. The transverse flow oil separator
      can intensify oil droplets combination and shorten rising time. The locale
      experiments showed the separator was suitable for dealing with oily wastewater of
      polymer flooding.

PMID- 12048824
TI  - [Degradation of 4-chlorophenol in aqueous solution by high-voltage pulsed
      discharge-ozone technology].
AB  - The combination of high voltage pulse discharge and ozonation as an advanced
      oxidation technology was used to investigate the degradation of 4-chlorophenol (4
      CP) in water. The factors that affect the rate of degradation were discussed. The
      1.95 x 10(-3) mol/L solutions of 4-CP were almost completely (96%) degraded after
      the discharge treatment of 30 min. The degradation of 4-CP was investigated as a
      function of the ozone concentration, radical scavenger and electrode distance.
      The rate of 4-CP degradation increases with an increase in ozone concentration
      and a decrease in the electrode distance from 20 mm to 10 mm. The presence of
      radical scavenger decreased the rate of 4-CP degradation.

PMID- 12048825
TI  - [Spacial distribution characteristics of soil organic matter and nitrogen in the
      natural floodplain wetland].
AB  - The spatial distribution characteristics of soil organic matter and nitrogen in
      the natural floodplain wetland were studied in this paper. The results showed
      that the vertical distributions of nutrients in floodplain wetland were very
      similar, and the horizontal distribution of them in surface soil were distinctly
      different. The highest concentration of nutrients was not in the frequently
      flooded floodplain wetland where the concentrations of soil organic matter and
      total nitrogen were 2.36% and 2605.4 mg/kg, but in the floodplain with a certain
      flood frequency. The concentrations of soil organic matter in the one-year
      floodplain wetland and five-year floodplain wetland were 3.70% and 3.92%,
      respectively; and the concentrations of total nitrogen were 3666.4 mg/kg and
      3125.6 mg/kg, respectively. The ratios of carbon and nitrogen were relatively
      low. All the factors such as cycling of dry and wet, underground underset,
      vegetation growth and pH values etc. influenced the distribution of soil organic
      matter and nitrogen in wetland.

PMID- 12048826
TI  - [Adsorption behavior of reactive X-3B red dye in soil environment and relevant
      influencing factors].
AB  - The determination of rates of soil adsorbing reactive X-3B red dye opened out
      that the adsorption of the dye by soils could be divided into four stages: high
      speed adsorption, slowdown adsorption, slow-speed adsorption and zero adsorption.
      There was a great difference in adsorptive rates between various soil types
      during these different stages. The research on adsorptive isotherms of reactive X
      3B red dye pointed out that adsorptive behavior of the dye tallied with the
      Langmuir equation. The calculation on the basis of the adsorptive isotherms
      indicated that the maximum adsorption of the dye was in the sequence paddy soil >
      red soil > brown earth > cinnamon soil. As for relevant environmental factors
      influencing this adsorption, contents of organic matter and water in soils, soil
      pH and air temperature were involved. When soil organic matter or air temperature
      was reduced and soils were at neutral, runny or unwatered conditions, the
      adsorption of the dye on soils was decreased, thereby inhibiting the accumulation
      of the dye in soil environment.

PMID- 12048827
TI  - [Stability of HDTMA modified montmorillonite].
AB  - In order to probe the stability of organic montmorillonite, the nature
      montmorillonite was modified with hexadeeyltrimethylammonium (HDTMA) in different
      cation exchange capacity (CEC). The results of experiments showed that the
      stability of modified montmorillonite declined as its CEC was big and HDTMA was
      desorbed from 1.0 CEC modified montmorillonite. HDTMA bound to the
      montmorillonite surface was resistant to temperature(70 degrees C) and instable
      to strong ultrasonic and to vibrational intensity(180 r/min). The result also
      indicated that the stability of modified montmorillonite increased to NaCl(1.8
      mol/L) but decreased to CaCl2 (1.8 mol/L) and modified montmorillonite was more
      stable in high-pH environment(12.00) than in low-pH environment(2.06). On the
      basis of the results of these studies, low CEC modified montmorillonite appeared
      suitable as a sorbent for wastewater chemical treatment and as carrier for
      wastewater biotreatment in low stir environment.

PMID- 12048828
TI  - [Effect of Fe2O3 on photodegradation of gamma-666 in surface soils with low
      amount of organic substance].
AB  - The photodegradation of gamma-666 on surface soils with low amount of organic
      substance was studied. The results showed that photodegradation rate of gamma-666
      was fitted for pseudo one-order kinetics. The constants of photodegradation rates
      increased from 0.0052 h-1 to 0.0340 h-1 with the increase of Fe2O3 contents
      between 0.40% and 5.40% in soils. These results showed that Fe2O3 in soils with
      low amount of organic substance had remarkable catalysis on photodegradation of
      gamma-666.

PMID- 12048829
TI  - [Degradation of cyanobacterial peptide hepatotoxins by ferrate].
AB  - In this study, the effect of ferrate oxidation on stability of microcystins-LR
      (MCLR) in freeze-dried Oscillatoria amoena was investigated. The toxin was easily
      decomposed by oxidation with ferrate, and the stability depended on the dosage of
      ferrate and pH. Simultaneously the product Fe(OH)3 after ferrate oxidation could
      flocculate the organic compounds so that 50% TOC removal of the extract was
      reached. The low residual iron reflected the excellent results of coagulation and
      could meet the standard of drinking water. The results show that ferrate
      oxidation may be an effective and practical method for the removal of
      cyanobacterial peptide toxins from drinking water.

PMID- 12048830
TI  - Whether docs get more comes down to money.

PMID- 12048831
TI  - Lobbying drags GOP drug bill.

PMID- 12048832
TI  - Risky strategy? Collective-bargaining crackdown may backfire on FTC.

PMID- 12048833
TI  - States of frustration. More medical groups step up battle against insurers.

PMID- 12048834
TI  - Grim trends. QualChoice to fold last health plan, shutter doors.

PMID- 12048835
TI  - Nursing the nurse shortage. As feds collaborate, states and localities act on
      own.

PMID- 12048837
TI  - Reprocessors threatened. Bill could complicate reconditioning single-use devices.

PMID- 12048836
TI  - Questionable quality initiative. Nursing homes frustrated with CMS measures.

PMID- 12048838
TI  - Putting together the pieces. We need a comprehensive solution to a brewing crisis
      in healthcare.

PMID- 12048839
TI  - The HHS posse. Whether it's shooting from the hip or keeping a low profile,
      Thompson, Scully and Rehnquist are riding a new trail in healthcare policymaking.

PMID- 12048840
TI  - Mixed messages. Not-for-profit hospitals woo investors with turnaround stories,
      but don't spare details about future challenges.
AB  - West Penn Allegheny Health System's management team (left) told a turnaround
      story at the Non-Profit Health Care Investor Conference. The forum, which was
      launched in 2000 to woo skittish bond investors, reflects hospitals' ongoing
      challenge to temper their messages for different audiences.

PMID- 12048841
TI  - [Phenylketonuria outgrows childhood shoes. How much is diet still necessary?].

PMID- 12048842
TI  - [Vitamin supplements, protein preparations, carnitine and Co. What is the benefit
      for amateur athletes (interview by Dr. Ulrich Scharmer)].

PMID- 12048843
TI  - [Differential thoracic pain diagnosis. An internal medicine challenge].
AB  - In the event of chest pain developing, the task of initial evaluation must be
      either to confirm and treat an acute life-threatening condition, or to exclude
      it. The diagnosis of a harmless functional disorder can be established only after
      the exclusion of a number of cardiovascular, pulmonary or gastrointestinal
      conditions, as also infection or malignancy. Such an approach often requires
      cooperation with orthopedic surgeons, general surgeons, psychiatrists and also
      pain specialists.

PMID- 12048844
TI  - [Rapid assessment of thoracic pain. Is it a myocardial infarct?].
AB  - The high mortality rate of acute myocardial infarction underline the importance
      of this entity in the differential diagnosis of acute chest pain. Medical
      history, clinical presentation, ECG, biochemical markers of myocardial injury and
      imaging techniques are used to establish a correct diagnosis. Myocardial
      infarction can be divided into ST-segment elevation myocardial infarction and non
      ST-segment elevation myocardial infarction. In the case of ST-segment elevation
      myocardial infarction thrombolytic therapy or percutaneous transluminal coronary
      angioplasty should be instituted as soon as possible. In patients without
      persistent ST-segment elevation biochemical markers of myocardial damage,
      especially troponin T and troponin I, are of major importance for risk
      stratification. Patients with elevated troponin levels should be treated with
      GPIIb/IIIa antagonists and early intervention.

PMID- 12048845
TI  - [Often an orthopedic problem can manifest as chest pain. Cervical vertebrae
      syndrome mimics myocardial infarct].
AB  - Up to 20% of all patients with pectoral symptoms have an underlying orthopedic
      problem. The most common orthopedic conditions that may mimic chest pain
      radiating into the left arm include slipped disc, cervicothoracic tension
      syndrome, blockage of intervertebral or rib joints, and intercostal neuralgia.
      Less common causes of such pain are arthrosis of the shoulder, spondylocystitis,
      osteoporotic fractures or tumors of the bone. Management is oriented to the
      underlying cause, and treatment extends from physiotherapeutic measures (rest,
      heat treatment) via medication (non-steroidal anti-inflammatory drugs,
      myotonolytic agents) to operative interventions.

PMID- 12048846
TI  - [Patient education, medication and physical therapy. Balm for "cardiac
      neurosis"].
AB  - In the management of psychogenic chest pain, the family doctor has a key role to
      play. His main task is to exclude physical or organic causes and identify the
      underlying psychogenesis--admittedly without wishing to establish a definitive
      (ICD-10) diagnosis. For this purpose, empathic reassurance of the patient is of
      major importance. Wherever possible, hospitalization of the patient for a
      diagnostic clarification should be avoided. Therapeutic options comprise suitable
      physiotherapy, psychohygienic measures, and appropriate pharmacotherapy. Major
      goals of such an approach are the establishment of a trusting relationship, and
      improving the patient's sleep patterns, physical fitness and emotional status. In
      the event of long-term persistence of the condition or a severe course, referral
      to a specialist is indicated.

PMID- 12048847
TI  - [Alopecia and hirsutism. Grief with beautiful hair].

PMID- 12048848
TI  - [Weight reduction in type 2 diabetes. Much more important than blood glucose
      monitoring].

PMID- 12048849
TI  - [Standard tests in geriatrics. 5: Parkinson Screening Questionnaire (PSQ)].

PMID- 12048850
TI  - [Elderly man with movement and bone pain. Only degenerative arthritis
      manifestations?].

PMID- 12048851
TI  - [Alternative and innovative treatment methods. Who pays when federal insurance
      doesn't pay?].

PMID- 12048852
TI  - [Federal committee physicians and insurance. Secret rationing].

PMID- 12048853
TI  - [Sartans for lowering blood pressure. Hypertensive patients need not fear
      potency].

PMID- 12048854
TI  - [Better prognosis for patients with chronic renal failure. "Preventive
      transplantation" instead of dialysis].

PMID- 12048855
TI  - [Hay fever and asthma. Many of your patients have both].

PMID- 12048856
TI  - [Dementia therapy. Colleagues are very reticent about using drugs].

PMID- 12048857
TI  - [Oil for control of house dust allergy. Bitter meal for mites].

PMID- 12048858
TI  - [Convenient and well-tolerated therapy of osteoporosis. Preventing fractures only
      once a week].

PMID- 12048859
TI  - [Fibromyalgia problem case. Monotherapy is mostly insufficient].

PMID- 12048860
TI  - [Cortisone properly inhaled? One can see, hear, taste this].

PMID- 12048861
TI  - [Colleague Zinecker promises rapid help with diverse general practice problems.
      "Magic" with local anesthetics].

PMID- 12048862
TI  - [31. Abdominal pain: how to determine the correct diagnosis?].

PMID- 12048863
TI  - Bayesian methods for missing covariates in cure rate models.
AB  - We propose methods for Bayesian inference for missing covariate data with a novel
      class of semiparametric survival models with a cure fraction. We allow the
      missing covariates to be either categorical or continuous and specify a
      parametric distribution for the covariates that is written as a sequence of one
      dimensional conditional distributions. We assume that the missing covariates are
      missing at random (MAR) throughout. We propose an informative class of joint
      prior distributions for the regression coefficients and the parameters arising
      from the covariate distributions. The proposed class of priors are shown to be
      useful in recovering information on the missing covariates especially in
      situations where the missing data fraction is large. Properties of the proposed
      prior and resulting posterior distributions are examined. Also, model checking
      techniques are proposed for sensitivity analyses and for checking the goodness of
      fit of a particular model. Specifically, we extend the Conditional Predictive
      Ordinate (CPO) statistic to assess goodness of fit in the presence of missing
      covariate data. Computational techniques using the Gibbs sampler are implemented.
      A real data set involving a melanoma cancer clinical trial is examined to
      demonstrate the methodology.

PMID- 12048864
TI  - Testing equality of cause-specific hazard rates corresponding to m competing
      risks among K groups.
AB  - In this paper, a class of tests is developed for comparing the cause-specific
      hazard rates of m competing risks simultaneously in K (> or = 2) groups. The data
      available for a unit are the failure time of the unit along with the identifier
      of the risk claiming the failure. In practice, the failure time data are
      generally right censored. The tests are based on the difference between the
      weighted averages of the cause-specific hazard rates corresponding to each risk.
      No assumption regarding the dependence of the competing risks is made. It is
      shown that the proposed test statistic has asymptotically chi-squared
      distribution. The proposed test is shown to be optimal for a specific type of
      local alternatives. The choice of weight function is also discussed. A simulation
      study is carried out using multivariate Gumbel distribution to compare the
      optimal weight function with a proposed weight function which is to be used in
      practice. Also, the proposed test is applied to real data on the termination of
      an intrauterine device.

PMID- 12048865
TI  - Hierarchical-likelihood approach for mixed linear models with censored data.
AB  - Mixed linear models describe the dependence via random effects in multivariate
      normal survival data. Recently they have received considerable attention in the
      biomedical literature. They model the conditional survival times, whereas the
      alternative frailty model uses the conditional hazard rate. We develop an
      inferential method for the mixed linear model via Lee and Nelder's (1996)
      hierarchical-likelihood (h-likelihood). Simulation and a practical example are
      presented to illustrate the new method.

PMID- 12048866
TI  - Parametric modeling for survival with competing risks and masked failure causes.
AB  - We consider a life testing situation in which systems are subject to failure from
      independent competing risks. Following a failure, immediate (stage-1) procedures
      are used in an attempt to reach a definitive diagnosis. If these procedures fail
      to result in a diagnosis, this phenomenon is called masking. Stage-2 procedures,
      such as failure analysis or autopsy, provide definitive diagnosis for a sample of
      the masked cases. We show how stage-1 and stage-2 information can be combined to
      provide statistical inference about (a) survival functions of the individual
      risks, (b) the proportions of failures associated with individual risks and (c)
      probability, for a specified masked case, that each of the masked competing risks
      is responsible for the failure. Our development is based on parametric
      distributional assumptions and the special case for which the failure times for
      the competing risks have a Weibull distribution is discussed in detail.

PMID- 12048867
TI  - Joint modeling of event time and nonignorable missing longitudinal data.
AB  - Survival studies usually collect on each participant, both duration until some
      terminal event and repeated measures of a time-dependent covariate. Such a
      covariate is referred to as an internal time-dependent covariate. Usually, some
      subjects drop out of the study before occurrence of the terminal event of
      interest. One may then wish to evaluate the relationship between time to dropout
      and the internal covariate. The Cox model is a standard framework for that
      purpose. Here, we address this problem in situations where the value of the
      covariate at dropout is unobserved. We suggest a joint model which combines a
      first-order Markov model for the longitudinally measured covariate with a time
      dependent Cox model for the dropout process. We consider maximum likelihood
      estimation in this model and show how estimation can be carried out via the EM
      algorithm. We state that the suggested joint model may have applications in the
      context of longitudinal data with nonignorable dropout. Indeed, it can be viewed
      as generalizing Diggle and Kenward's model (1994) to situations where dropout may
      occur at any point in time and may be censored. Hence we apply both models and
      compare their results on a data set concerning longitudinal measurements among
      patients in a cancer clinical trial.

PMID- 12048868
TI  - Managing technological explosion in the medical management of coronary artery
      disease. Cardiovascular administrators are key internal consultants in planning
      for drug-eluting stent technology.

PMID- 12048870
TI  - Implementing a service line management model for cardiothoracic surgery and
      cardiology.

PMID- 12048869
TI  - Reducing the cost of cardiac procedures.

PMID- 12048871
TI  - Expectations and assumptions: the termites of strategy.

PMID- 12048872
TI  - [Present status and prospective view of living-donor liver transplantation].

PMID- 12048873
TI  - [Quality of life in long-term survivors of pediatric living related-donor liver
      transplantation].
AB  - In this study, we discuss the quality of life with reference to the growth of
      long-term survivors to evaluate the prognosis of liver transplantation. Nine of
      41 pediatric patients who received living related-donor liver transplantation
      (LRLT) in our institution from 1991 to the present are now in alive more than 6
      years after surgery. Their quality of life, physical development, liver function,
      and need for immunosuppressive therapy were analyzed. Physical growth is improved
      by LRLT, although it still does not to reach the mean level in Japan. Three of
      the nine patients were successfully withdrawn from immunosuppressive drugs,
      although one required readministration. Two patients exhibited side effects of
      steroid administration: one experienced renal lithiasis, and another developed
      cataracts. One patient needed surgery for ileus, and three had varicella
      infections. One of 2 patients who received an ABO-incompatible graft continues to
      show unstable liver function after 9 years. In summary, LRLT is effective in
      improving the physical growth and the quality of life of patients, but problems
      remain in their daily lives. In particular, we need to adapt the timing of
      surgery to take account of physical growth and to discuss the timing of
      vaccinations to prevent viral infection.

PMID- 12048874
TI  - [Adult living donor liver transplantation].
AB  - The number of adult living-donor liver transplantations is rapidly increasing
      world wide. Donor selection, technical innovation, and postoperative management
      are important for donor safety. The adequacy of graft size is the major
      limitation and the most critical issue in adult living-donor liver
      transplantation. The outcome of this surgery is significantly influenced by the
      pretransplant patient condition and the original patient disease. Further study
      is needed to clarify the indications for and timing of living-donor
      transplantation for adult recipients.

PMID- 12048875
TI  - [Liver transplantation for fulminant hepatitis].
AB  - Liver transplantation has been recognized as an effective therapeutic method for
      end-stage liver disease in Japan. Fulminant hepatic failure is also an indication
      for liver transplantation, and the number of patients undergoing liver
      transplantation has been increasing. Reversibility and urgency are
      characteristics of fulminant hepatitis. If given appropriate critical support,
      many patients recover spontaneously. However, many patients develop cerebral
      edema or multiorgan failure before the liver can regenerate. Indications,
      operative procedures, and outcome of liver transplantation for fulminant
      hepatitis are discussed here. At Shinshu University, 23 of 169 cases of liver
      transplantation were for fulminant hepatitis. One transplantation was from a
      cadaveric donor and 22 from living donors. The actuarial 5-year patient and graft
      survival rate was 85.4%. Although some problems remain in liver transplantation
      for fulminant hepatitis, the results are better than those of conventional
      therapy. Therefore patients with fulminant hepatic failure should be listed for
      liver transplantation when grade 2 hepatic encephalopathy develops. Moreover, in
      cases of severe acute hepatitis, i.e., before patients develop grade 2
      encephalopathy, liver transplantation should be considered among choices of
      therapy in the near future.

PMID- 12048876
TI  - [Liver transplantation for patients with hepatitis B/C virus cirrhosis or hepato
      cellular carcinoma].
AB  - The outcome of liver transplantation for patients with hepatitis B/C virus
      (HBV/HBC) cirrhosis or with hepatocellular carcinoma(HCC) was deemed pessimistic
      until the early 1990s due to the high rate of recurrence and mortality. However,
      with the advent of new antiviral agents and strict adherence transplant
      indications, the results of liver transplantation in patients with these disease
      have improved progressively. Coadministration of lamivudine and anti-HBV
      immunoglobulin, and of interferon and ribavirin inhibits the recurrence of
      hepatitis B and hepatitis C, respectively. Excluding HCC patients with
      extrahepatic or lymph node metastasis, vascular invasion, a single lesion more
      than 5 cm in diameter, or multiple lesions more than 3 cm in diameter, the 5-year
      patient survival rate has improved from 30% to 85%, with a disease-free survival
      rate of more than 90%. However, the development of lamivudineresistant mutants
      after prolonged use of the agent needs to be overcome, possibly by new antiviral
      agents such as adefovir. In addition, to expand the current limited transplant
      indications for HCC, the efficacy of perioperative anticancer treatment and the
      importance of molecular diagnosis of circulating hepatoma cells must be
      determined in future.

PMID- 12048877
TI  - [ABO-incompatible liver transplantation and patients with hepatopulmonary
      syndrome].
AB  - From 1991 to 2000, more than 100 ABO-incompatible liver transplantations were
      performed in 12 institution in Japan. The overall survival rate is 60%. Survival
      data appear to have improved in these years even in adult cases, although acute
      vascular rejection causing hepatic necrosis, infection, and intrahepatic bile
      duct injury are major complications to be resolved. Hepatopulmonary syndrome
      (HPS) was considered to be a contraindication to transplantation in the 1980s.
      However, even severe cases can recover from hypoxia after liver transplantation,
      and improved survival data were reported in the 1990s. Intensive respiratory
      therapy after transplantation with NO inhalation allows expansion of the
      indications for transplantation in HPS.

PMID- 12048878
TI  - [Small-for-size graft problems in adult-to-adult living donor liver
      transplantation].
AB  - A major concern regarding adult living donor liver transplantation is graft-size
      disparity. The right liver graft is now commonly used, which might impose a risk
      on the donors. In selected cases, the left liver with caudate lobe and right
      lateral sector graft might alleviate the problem without increasing the risk to
      donors.

PMID- 12048879
TI  - [Domino and split liver transplantation: technical problems].
AB  - Because the shortage of donor livers has been the rate-limiting factor in the
      expansion of liver transplantation, several innovative techniques including
      reduced, split, and living donor liver transplantation have been developed to
      expand the relatively constant pool of organs. Domino liver transplantation,
      which was first reported from Portugal in 1995, has been performed worldwide and
      allows a donor organ to be used for a subsequent graft in a second liver
      recipient. Domino liver transplantation involves specific ethical and technical
      problems. The most important ethical problem in the procedure is the use of a
      diseased liver (e.g., familial amyloid polyneuropathy [FAP]) for a second
      recipient. Furthermore, the safety of the first recipient (FAP patient) should be
      the primary consideration. From the technical point of view, the management of
      short vascular cuffs is important, especially in domino liver transplantation
      from a living donor. The results of split liver transplantation have
      significantly improved and it is now recognized as an ideal method to expand the
      donor pool, especially for small children. Either the ex vivo or in vivo
      technique can be used with comparable results.

PMID- 12048880
TI  - [Infection and rejection].
AB  - Forty-one living donor liver transplantations (LDLT), including 11 pediatric and
      30 adult recipients, were performed in Okayama University Hospital. Thirty-seven
      patients survive (overall survival rate 90.2%). Postoperative infection and
      rejection were analyzed. The incidence of bacterial and cytomegalovirus infection
      was 26.8% and 22%, respectively, but no patient developed lethal infection.
      Posttransplant lymphoproliferative disease occurred in 3 recipients who received
      additional pre- or postoperative intensive immunosuppressive therapy. Even though
      all recipients were administered a tacrolimus-based double or triple regimen
      including prophylactic programmed pulse therapy (methylpredonisone 10 mg/kg, days
      5 to 7), 30 rejection episodes were observed in 19 patients(46.3%). Two
      recipients died of both steroid- and OKT-3-resistant rejection. Routine daily
      Doppler ultrasonography (US) revealed the presence of early severe rejection with
      hepatic hemodynamic changes in 7 patients. Patients exhibiting rejection with
      hemodynamic changes had a significantly shorter incubation period (8.8 +/- 2.2 vs
      38.7 +/- 29.6 days, p < 0.01), more severe histological features(rejection
      activity index, 6.1 +/- 1.2 vs 3.0 +/- 0.5, p < 0.001), and higher peak alanine
      aminotransferase value (883 +/- 354 IU/L vs 198 +/- 115 IU/L, p < 0.01) than in
      those exhibiting rejection without hemodynamic changes. Diagnostic programmed
      pulse therapy plus frequent routine Doppler US may be useful in the diagnosis of
      and therapy for earlier and more severe acute rejection in LDLT.

PMID- 12048881
TI  - [Treatment of vascular and biliary complications following living related-donor
      liver transplantation].
AB  - Surgery for living related-donor liver transplantation(LRDLT) is difficult
      compared with orthotopic whole-liver transplantation. It is necessary to find
      methods both to prevent and treat vascular and biliary complications.
      Interventional radiological procedures have been increasingly used in recent
      years for the diagnosis and nonsurgical treatment of these complications, with
      encouraging results. Vascular complications include technical device of
      stricture, obstruction, and thrombosis. Hepatic arterial reconstruction requires
      great skill in LRDLT, although in the author's experience a surgical loupe may
      suffice for reconstruction in adult LRDLT if the surgeon has sufficient
      experience in microvascular surgery. Early postoperative life-threatening
      vascular complications must be treated urgently, including further surgery.
      Recently duct-to-duct (D-D) biliary reconstruction has been performed in addition
      to hepatico-jejunostomy in LRDLT. D-D anastomosis has the advantages of simple
      operative technique shorter duration of surgery, simple postoperative management,
      normal physiologic route, and elimination of reflux cholangitis.

PMID- 12048882
TI  - [Assessing liver function by magnetic resonance imaging two-dimensional phase
      shift flow measurement of portal venous blood flow after oral intake of glucose].
AB  - We have already reported that the ratio of portal venous flow 30 min after oral
      intake of glucose 75 g to that before intake (PVFR30), measured using pulsed
      Doppler ultrasonography (US), correlated significantly with other indicators of
      liver function and that it could be used to estimate hepatic function before
      surgery, including liver resection. In this study, to assess the disadvantages of
      pulsed-Doppler ultrasonography, PVFR30 was measured using two-dimensional (2D)
      phase-shift (PS) magnetic resonance imaging (MRI). PVFR30 was measured in 17
      patients and 7 volunteers: 13 with liver cirrhosis (LC) and 11 without LC (non
      LC). Portal venous flow could be measured in all patients without any disturbance
      of intestinal gas or patient fat, or the high degree of technical skill that
      Doppler US requires. PVFR30 was significantly lower in the LC group than in the
      non-LC group. In addition, it correlated significantly with other indicators of
      liver function, including the indocyanine green clearance test, prothrombin time,
      hepaplastin test, and cholinesterase activity. These results suggest that PVFR30
      measured by 2D PS MRI can be used to estimate liver function, and that this MRI
      method can be performed more easily than pulsed-Doppler US.

PMID- 12048884
TI  - [A revised genealogy of Julius Scriba, a benefactor who promoted Japan Surgical
      Society in Meiji era].

PMID- 12048883
TI  - [Evaluation of the efficacy of TS-1 for peritoneal dissemination of gastric
      cancer using a newly-developed animal model].

PMID- 12048885
TI  - [Studies on the actin-based spreading of Shigella].

PMID- 12048886
TI  - [Postgenomic approach for bacterial drug resistance factors based on drug
      exporters and two-component signal transduction systems].

PMID- 12048887
TI  - [Typings of Campylobacter jejuni isolated from patients of 2 outbreak cases by
      genotypic and phenotypic methods].
AB  - We compared Campylobacter jejuni strains isolated from the patient stools
      associated with two food-borne diarrheal outbreak cases by the serotypic methods
      (Lior and Penner systems) and the genotypic methods (restriction fragment length
      polymorphism (RFLP) of flaA gene and pulsed-field gel electrophoresis (PFGE)).
      Fla-RFLP was based on the digestion of 410 bp DNA fragment by MboI restriction
      enzyme amplified from a 5' portion of C. jejuni flaA gene. Six distinctive fla
      RFLP patterns were identified by examining 29 serotype reference strains and 58
      strains isolated from the patients infected with C. jejuni independently. In the
      first outbreak case, 4 isolates were shown to be the same patterns each other by
      the fla-RFLP and PFGE, and by the Lior serotyping, except the Penner system that
      serotyped into 2 distinct types. On the other hand, in the second case, out of 10
      isolates, 5 isolates were identical by the both genotypic and the both serotypic
      methods, and 4 isolates were not differentiated by the fla-RFLP and Penner
      system, but were separated into 4 types by PFGE in a little difference. The rest
      isolate was completely different from the other isolates by the all of methods
      used now. The findings suggest that the second case occurred by the infection of
      at least 3 different strains of C. jejuni.

PMID- 12048888
TI  - [New trends in diagnosis and treatment of depressed and flat type neoplasms in
      colon and rectum].

PMID- 12048889
TI  - [Genetic backgrounds in superficial- and superficial depressed-type colorectal
      cancer].

PMID- 12048890
TI  - [Long-term efficacy of transjugular intrahepatic portosystemic shunt for the
      treatment of refractory ascites].
AB  - Eighteen patients with refractory ascites (Child-Pugh score 9.9) defined by our
      criteria were treated with transjugular intrahepatic portosystemic shunt (TIPS).
      The long-term efficacy of the treatment was studied in these patients. The
      complete and partial response rate of refractory ascites was 73% at 6 months, 90%
      at 1 year and 100% at 2 years. The cumulative survival rate was 89% at 6 months,
      78% at 1 year and 48% at 2 years. A statistically significant(p < 0.05) increase
      was observed in performance status score following TIPS: Mean performance status
      score prior to TIPS was 43%, as opposed to 62% at 3 months after TIPS and 85% at
      2 years. Child-Pugh score and liver function tests showed no significant change.
      During follow-up, shunt stenosis was noted in 14 patients, requiring shunt
      revision. Ascites recurrence was observed in 70% of patients with shunt stenosis
      and shunt revision resulted in good control of ascites. Post-TIPS encephalopathy
      was seen in 15 patients during follow-up. In conclusion, TIPS is effective on the
      treatment of refractory ascites and results in an improvement in quality of life.
      TIPS also may improve survival of the patients with refractory ascites. However,
      shunt stenosis and encephalopathy are common and require careful follow-up and
      adequate treatment.

PMID- 12048891
TI  - [A case report of cytomegalovirus-associated gastritis in a normal adult].

PMID- 12048892
TI  - [A case of mesentric arteriovenous malformation with portal hypertension].

PMID- 12048893
TI  - [An autopsy case of allergic granulomatous angitis (Churg Strauss syndrome) with
      heart failure and HSV infection following perforation of the small intestine].

PMID- 12048894
TI  - [A case report of ulcerative colitis accompanied by goblet cell carcinoid and
      adenocarcinoma].

PMID- 12048895
TI  - [A case of combined liver cell and bile duct carcinoma detected 6 years after
      interferon therapy for chronic hepatitis C, in spite of showing complete
      response].

PMID- 12048896
TI  - [Three cases of the primary splenic malignant lymphoma: associated with hepatitis
      C virus infection].

PMID- 12048897
TI  - [Multiple cancer of the common bile duct associated with clonorchiasis].

PMID- 12048898
TI  - [A case of groove pancreatitis with fibromuscular proliferation].

PMID- 12048899
TI  - [Forty-six months follow up of a patient with pancreatic lymphoepithelial cyst].

PMID- 12048900
TI  - [Comparison of clinical and angiographic outcomes between S670 and NIR stents].
AB  - OBJECTIVES: This study evaluated the long-term outcomes of successfully implanted
      S670 and NIR stents. METHODS: Stents were successfully implanted in 143 patients
      (148 lesions) aged 65 +/- 9 years from January 1999 to April 2001. Sixty-eight
      lesions were treated with S670 stents and 80 with NIR stents. Quantitative
      coronary angiography was performed before, immediately after and 6 months after
      implantation. An angiographic classification of in-stent restenosis was developed
      according to the geographic distribution of intimal hyperplasia in reference to
      the implanted stent. Furthermore, the relationships between stent diameter and
      length and restenosis rate were estimated. RESULTS: Type B2/C lesions were
      significantly more common in patients with S 670 (77.3%) stents compared with NIR
      (43.6%). Stent length was longer and diameter was smaller in patients with S 670
      stents compared with those with NIR stents. Acute-gain was similar in the two
      groups, but late-loss was significantly greater in patients with S 670 stents
      compared with those with NIR stents. Restenosis rate and target lesion
      revascularization rate were similar in the two groups. The diffuse type of
      restenosis lesion was frequently found in S 670 stents. The stent diameter, but
      not stent length, influenced the restenosis rate in S 670 stents. Both stent
      length and diameter influenced the restenosis rate in NIR stents. CONCLUSIONS:
      Late-loss was larger and in-stent restenosis of diffuse type was significantly
      greater in S 670 stents compared with NIR stents. However, stent length was
      significantly longer and type B2/C lesions were significantly greater in S 670
      stents compared with NIR stents. There was no difference in restenosis rate and
      target lesion revascularization rate. In addition, restenosis rate was not
      influenced by stent length in S 670 stents, so S 670 stents may be useful for
      complex lesions.

PMID- 12048901
TI  - Effects of carvedilol on plasma levels of interleukin-6 and tumor necrosis factor
      alpha in nine patients with dilated cardiomyopathy.
AB  - OBJECTIVES: Whether beta-blocker therapy changes the circulating levels of
      cytokines as congestive heart failure improves remains uncertain. METHODS: Nine
      patients with idiopathic dilated cardiomyopathy, who had previously received
      conventional treatment and were classified as New York Heart Association (NYHA)
      functional class II, received carvedilol by stepwise dose increase up to 20 mg
      daily, and the plasma interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF
      alpha) levels were measured. RESULTS: IL-6 was significantly reduced from 0.80 +/
      0.49 pg/ml before therapy to 0.21 +/- 0.08 pg/ml after carvedilol was increased
      to 20 mg daily (p < 0.05). Moreover, IL-6 level had already decreased
      significantly compared to the baseline when the dose of carvedilol had reached 10
      mg daily (0.28 +/- 0.12 pg/ml, p < 0.05). TNF-alpha levels did not change
      significantly. CONCLUSIONS: These results demonstrate that IL-6 concentration is
      significantly decreased by beta-blocker therapy. The efficacy for heart failure
      may be related to the change of IL-6 concentration.

PMID- 12048902
TI  - [Social concern and independence in adults with congenital heart disease].
AB  - OBJECTIVES: Recent advances in medical and surgical treatment have led to the
      survival of increasing numbers of adults with congenital heart disease (CHD).
      However, the social status of these patients remains unknown. This survey
      investigated the social prospects for adults with CHD, and the limiting factors
      for social independence. METHODS: A written questionnaire on patient
      characteristics, education, employability, marital status and insurability was
      designed to define the characteristics of social independence in adults with CHD.
      Randomly selected adults with CHD were enrolled: 13 patients with cyanotic
      unrepaired CHD (4 males, 9 females, mean age: 29.8 +/- 10 years, range: 18-56
      years) and 102 patients with other CHDs (48 males, 54 females, mean age: 29.5 +/-
      10 years, range: 18-74 years). RESULTS: University of California at Los Angeles
      functional class I-II was found in 94% of patients, medication in 46%, and
      hospitalization in 51%. Compared with the data from Japanese general population,
      study patients had a lower ratio of high school graduates (86% vs 94%), life
      insurability (51% vs 71%), marital status (31% vs 32%) and employability (82% vs
      80%). Patients with unrepaired cyanotic CHD had significantly lower ratio than
      those with other CHDs (marital status 15%, p = 0.19; employability 40%, p =
      0.0003; high school graduates 69%, p = 0.06; life insurability 18%, p = 0.02,
      respectively). CONCLUSIONS: Factors affecting social independence in adults with
      CHD were severity of disease, continuing medication, lower level of education,
      lower self-esteem, and unknown natural history of CHD. To improve social
      independence in these patients, further development of medical and surgical
      therapy and more detailed knowledge of the patients, caretakers and society in
      this field are needed.

PMID- 12048903
TI  - Reversible subacute effusive-constrictive pericarditis after correction of double
      chambered right ventricle: a case report.
AB  - A 15-year-old girl developed subacute constrictive pericarditis following
      successful surgical repair of double-chambered right ventricle. Two weeks after
      surgery, the patient had massive pericardial effusion, which acutely progressed
      to constrictive pericarditis with the symptoms of cardiac tamponade. Further
      surgery was necessary to resect the parietal pericardium. No blood transfusion
      was required for this patient, who was a Jehovah's Witness. She was doing well 9
      months after the second operation, with residual pericardium of normal thickness.

PMID- 12048904
TI  - [Pulmonary pseudosequestration receiving arterial supply from the right coronary
      artery: a case report].
AB  - A 66-year-old female had been treated by hemodialysis since 1996. She was
      admitted to our hospital with acute pneumonia in January 2001. During admission,
      ischemic heart disease was identified. Her condition deteriorated and organic
      pneumonia of the right middle lobe progressed. She recovered after 6 months and
      coronary arteriography was performed. A 90% stenosis was detected at the ostium
      of the right coronary artery. An aberrant tortuous artery arose from the distal
      sinus node artery, and drained into the lung network, but also partially drained
      to the right segmental pulmonary artery branch. The diagnosis was significant
      stenosis of the right coronary artery, and pulmonary pseudosequestration or
      pulmonary sequestration receiving arterial supply from the sinus node artery.
      Surgical revascularization, ligation of the aberrant artery, and partial
      resection of the right middle lobe were performed. However, intraoperative
      findings did not identify the pulmonary sequestration. This rare case of
      pulmonary pseudosequestration received the arterial supply from the sinus node
      artery, originating from the right coronary artery with a significant stenotic
      lesion, and developed without recurrent pneumonia.

PMID- 12048905
TI  - Angina pectoris or myocardial infarction? Pure septal infarction.

PMID- 12048906
TI  - [A 42-year-old man with cardiac systolic murmur and a mediastinal tumor. Invasive
      thymoma (predominantly epithelial type, clinical stage IVa)].

PMID- 12048907
TI  - Oral quinidine therapy for chronic atrial fibrillation.

PMID- 12048908
TI  - [Future aspect of robotic surgery].
AB  - Minimally invasive surgery has become a standard options of surgery. We have
      introduced a master-slave manipulator "da Vinci" to the clinical situation in
      July 2000, and developed new operative techniques, which are safer and more
      tender for patients than before. Up to now, a total of 45 patients underwent a
      robot-assisted endoscopic surgery using "da Vinci" system. Several procedures
      including laparoscopic splenectomy and thoracoscopic mediastinal tumor
      extirpation were first performed in the world. This system provided surgeons with
      motion scaling, physiological tremor elimination, and high-resolution 3
      dimensional vision. Thanks to those sophisticated functions, all surgical
      procedures, which have been limited due to endoscopic circumstances, were
      performed much easily and safely than before. Every effort to develop a new type
      of robotic has been made in collaboration with other fields of scientists. A next
      generation robotic surgery is required to equip new functions including tactile
      sensation system, a real-time navigation system and tele-operation system.
      Robotic surgery is believed to be one of the most promising and important fields
      of surgery in the near future.

PMID- 12048909
TI  - Taste dysfunction in irradiated patients with head and neck cancer.
AB  - Taste disorders caused by radiation therapy for head and neck cancer are common.
      This prospective study of 40 patients with head and neck cancer assessed changes
      in taste sensations during radiation therapy. The relationship between the time
      course and the degree of taste disorder was studied. The taste recognition
      threshold and supra-threshold taste intensity performance for the four basic
      tastes were measured using the whole-mouth taste method before, during, and after
      radiation therapy. Bitter taste was affected most. An increase in threshold for
      sweet taste depended upon whether the tip of tongue was included within the
      radiation field. The slope of the taste intensity performance did not change
      during or after radiotherapy. The pattern of salivary dysfunction was different
      from that of taste dysfunction. The main cause of taste disorders during
      radiation support the hypothesis that taste dysfunction is due to damage to the
      taste buds in the radiation field.

PMID- 12048910
TI  - Oncological significance of WHO histological thymoma classification. A clinical
      study based on 286 patients.
AB  - OBJECTIVES: The clinical significance of thymoma histology remains controversial
      because of the numerous histological classifications of thymic epithelial tumors.
      Universal classification of such tumors was achieved by the World Health
      Organization (WHO) in 1999. We studied the prognostic significance of this
      classification. METHODS: We studied clinical features and postoperative survival
      in cases of thymoma, but not thymic carcinoma, based on WHO histological
      classification in 286 patients undergoing surgery between 1958 and 2001. RESULTS:
      Tumors were 19 type A, 79 type AB, 59 type B1, 102 type B2, and 27 type B3. The
      proportion of invasive tumors increased by type--from A to AB, B1, B2, and B3.
      The great vessels were involved more frequently in type B2 and B3 tumors than in
      type A, AB, and B1 tumors. The 20-year survival was 100% in type A, 87% in type
      AB, 91% in type B1, 65% in type B2, and 38% in type B3 tumors. Multivariate
      analysis showed Masaoka staging and WHO histological classification to be
      significant independent prognostic factors, while age, gender, myasthenia gravis
      association, resection completeness and great vessel involvement were not. In
      stage III patients, 13 of 45 patients with type B2 and B3 tumor died of their
      tumors, while no tumor deaths occurred in 11 patients with type A, AB, and B1
      tumors. CONCLUSION: WHO histological classification realistically reflects the
      oncological behavior of thymoma.

PMID- 12048911
TI  - Late aortic root redissection following surgical treatment for acute type A
      aortic dissection using Gelatin-Resorcin-Formalin glue.
AB  - OBJECTIVES: Although Gelatin-Resorcin-Formalin (GRF) glue is widely used in
      surgery for acute aortic dissection, late complications possibly due to the glue,
      such as late aortic root redissection, have also been reported. We have
      experienced similar complications, some of which required redo surgeries, and
      these cases are reviewed. METHODS: Twenty-six consecutive patients who underwent
      surgery for acute type A aortic dissection using GRF glue, from December 1996 to
      February 2001, were retrospectively studied, with a special focus on any late
      complications and any reoperation. RESULTS: Of the 21 patients who survived and
      were followed as outpatients, false aneurysms were found in 5 patients (21%) at
      24-42 (mean 34) months following the initial surgery. Of these, 2 patients
      required resternotomy because of the increasing aneurysm diameter. In both cases,
      the aortic root was redissected at the site of the GRF glue use where the
      anastomosis between the aortic root and the prosthesis had widely opened and had
      become the aneurysm entry point. Significant aortic regurgitation was noticed in
      3 patients (14%, 1 of whom showed a false aneurysm), and 2 of these underwent
      reoperation for aortic root redissection. CONCLUSIONS: A high incidence of aortic
      root redissection with false aneurysm and/or aortic insufficiency was found
      following the surgery for acute aortic dissection using GRF glue. These patients
      should be carefully followed for years after surgery.

PMID- 12048912
TI  - Adaptive immunity is severely impaired by open-heart surgery.
AB  - OBJECTIVE: The influence of open-heart surgery on antigen-specific immunity, also
      called adaptive immunity, remains to be clarified. We explored the effects of
      open-heart surgery on adaptive immunity. METHODS: In 8 consecutive adult patients
      undergoing elective cardiac surgery with cardiopulmonary bypass, we measured the
      T cell-response to purified protein derivative (PPD) antigen perioperatively. We
      separately measured the proliferation of T cells and the antigen presentation of
      antigen-presenting cells (APCs) using a cross-reaction system. RESULTS: T cell
      response to PPD antigen was severely impaired by open-heart surgery. Compared to
      preoperative values, T cell response to PPD antigen fell to 5.7 +/- 4.4%
      immediately after surgery, 4.5 +/- 3.2% on postoperative day (POD) 1, to 22.4 +/-
      24.6% on POD 3 and to 50.1 +/- 34.3% on POD 7. T cell proliferation on POD1
      decreased to 29 +/- 26%. APC antigen-presentation on POD 1 also decreased to 31
      +/- 36%. CONCLUSIONS: Open-heart surgery impaired both T cell proliferation and
      the antigen-presentation. Such synergistic impairment severely impaired adaptive
      immunity. This impairment was both severer and longer than we anticipated based
      on previous studies using the response of T cells to lectin as a marker of cell
      mediated immunity.

PMID- 12048913
TI  - Evaluation of inflammatory-response-induced thoracoscopic surgical stress.
AB  - OBJECTIVE: Due to the paucity of reports evaluating stress induced by
      thoracoscopic surgery with minithoracotomy, we assessed this stress based on the
      inflammatory response to surgery. METHODS: Differences in pre- and postoperative
      peripheral white blood cell (WBC) count, serum C-reactive protein (CRP), and
      serum interleukin-6 (IL-6) were evaluated, defined as dW, dCRP, and dIL-6.
      Thoracoscopic partial lung resection cases were divided into 2 groups by access
      route: Group A patients in which surgery was concluded via several small access
      ports. and Group B patients going surgery via small access ports plus
      minithoracotomy. We also compared dW in standard lobectomy with exploratory
      thoracotomy (thoracotomy without lobectomy) cases. RESULTS: No significant
      difference was seen in dW, dCRP, or dIL-6 between groups. dW in response to
      exploratory thoracotomy was lower than that in standard lobectomy (p = 0.06).
      CONCLUSIONS: Surgical stress induced by thoracoscopic partial lung resection does
      not increase significantly when minithoracotomy is added. Postoperative
      inflammatory response may, however, be influenced by the extent of surgical
      trauma.

PMID- 12048914
TI  - Myocardial infarction after cryoablation surgery for Wolff-Parkinson-White
      syndrome.
AB  - A 48-year-old woman with Wolff-Parkinson-White syndrome underwent surgical
      division of the accessory pathway in the left lateral wall. At 6 months after the
      procedure, she developed dyspnea and chest oppression. Coronary angiography
      revealed total occlusion in the left circumflex coronary artery (segment 13) at
      the exact site where cryoablation had been performed. The coronary occlusion was
      treated with an intracoronary bolus injection of urokinase (960,000 U) and
      subsequent percutaneous transluminal balloon angioplasty. No significant residual
      stenosis remained after the balloon angioplasty, and no further evidence of
      myocardial ischemia was noted for 13 years to date after the procedure.

PMID- 12048915
TI  - Successful surgical management of complete tracheal disruption due to penetrating
      injury.
AB  - Successful management of penetrating injury to the trachea is rare, especially in
      Japan. A 32-year-old female attempted suicide by stabbing herself in the throat
      with a knife, and at operation the trachea was found to be completely disrupted.
      A median sternotomy made possible end-to-end anastomosis of the trachea. All
      other important organs including the great vessels, esophagus, and lungs were
      intact, but the pleura was open on the right side. The patient was managed under
      heavy sedation and with controlled ventilation for more than a week
      postoperatively, because of her suspected mental condition. She was extubated on
      postoperative day 13 and transferred to a mental hospital on day 16. We concluded
      that early diagnosis and surgical repair were important for the successful
      management of this patient with tracheal disruption.

PMID- 12048916
TI  - Single primary lung cancer consisting of three cancer cell types (small cell
      carcinoma, adenocarcinoma, and squamous cell carcinoma) in which each had
      metastasized to different lymph nodes.
AB  - We report a case of a 70-year-old male smoker with a single primary tumor 2.5 x
      3.0 cm in size in the right lung lower lobe. A transbronchial lung biopsy
      revealed squamous cell carcinoma of the lung. We performed right lower lobectomy
      with lymph node dissection (ND2a). The resected specimen consisted of three
      different cell types; small cell carcinoma, adenocarcinoma and squamous cell
      carcinoma (in a ratio of 70: 20: 10). Each cancer cell types had metastasized to
      different lymph nodes. The final diagnosis was a combined small cell carcinoma in
      the lung. Combined small cell carcinoma is uncommon, but is nevertheless a well
      described diagnostic category in lung cancers.

PMID- 12048917
TI  - Successful surgical management of patients with infective endocarditis associated
      with acute neurologic deficits.
AB  - Subjects were 2 patients with neurologic deficits due to infective endocarditis.
      The first, a 30-year-old woman with acute ischemic stroke, was found to have
      vegetation from infective endocarditis as the embolic source. Two weeks after she
      experienced an acute ischemic stroke, we conducted elective cardiac surgery. The
      second, a 16-year-old girl with infective endocarditis, suffered a ruptured
      mycotic aneurysm in the left carotid system complicated by intracranial
      hemorrhage. We conducted a successful staged mitral valve replacement following
      craniotomy.

PMID- 12048918
TI  - Giant cell tumor of the rib.
AB  - In a rare case of a giant cell tumor of rib origin, a 25-year-old woman to be
      evaluated for an abnormal mass shadow in chest radiography was strongly positive
      in a tuberculin skin test, but showed no evidence of active tuberculosis. Chest
      computed tomography showed a heterogeneous mass originating in the posterior end
      of the right fourth rib and containing multiple calcifications and cystic
      lesions. Magnetic resonance imaging showed a high signal intensity with low
      signal intensity areas. Bone scintigraphy showed an abnormal marked accumulation
      at the tumor site. A thoracoscopic examination was conducted prior to complete
      tumor resection, including the fourth rib and related muscles. The pathological
      diagnosis returned was a giant cell tumor of the bone. The patient did not
      undergo chemotherapy or radiotherapy, and remains well, and tumor-free at 6
      months after surgery.

PMID- 12048919
TI  - Cardiac tamponade secondary to rupture of a distal aortic arch aneurysm.
AB  - We report the rare rupture of a distal aortic arch aneurysm protruding into the
      pericardial cavity. A 70-year-old woman who suddenly lost consciousness and was
      transferred to our hospital by ambulance in profound shock was found in emergency
      computed tomography and echocardiography to have a dilated distal aortic arch and
      massive pericardial effusion. Suspecting that a distal aortic arch aneurysm had
      ruptured, causing cardiac tamponade, we undertook an operation. We found a defect
      in the aneurysmal wall leading to the pericardium near the main pulmonary artery
      that was plugged temporarily with an atheromatous mass. We conducted total arch
      replacement successfully under selective cerebral perfusion and moderate
      hypothermia.

PMID- 12048920
TI  - [Problems on treatment of congenital cataract].

PMID- 12048921
TI  - [Gelatinous drop-like corneal dystrophy: mutation analysis of membrane component,
      chromosome 1, surface marker 1].
AB  - PURPOSE: To investigate mutation in membrane component, chromosome 1, surface
      marker 1(M1 S1) gene for patients and unaffected relatives of gelatinous drop
      like corneal dystrophy(GDLD). MATERIALS AND METHODS: We performed mutation
      analysis for 11 patients and 18 unaffected relatives from 7 unrelated families
      with GDLD. They were followed at the Department of Ophthalmology, Juntendo
      University, Tokyo, and St. Luke's International Hospital, Tokyo. RESULTS: Ten
      patients including the affected members of 6 families were detected to be
      homozygotes by transition of a C to T at nucleotide position 352, replacing a
      glutamine at codon 118 with a stop codon (Q118X), and unaffected relatives were
      heterozygous for the mutation. One patient and his parents and brother from one
      family have had no mutation in open reading frame of the M1S1 gene. CONCLUSIONS:
      In these 6 families the genotypes of Q118X mutation on M1S1 gene were co
      segregated with the phenotype. For the patients who have had no mutation, we need
      further investigation of the 5' upper site, and it is possible that there is
      another candidate gene for GDLD.

PMID- 12048922
TI  - [Intraocular lens power calculation and refractive change in pediatric cases].
AB  - PURPOSE: To evaluate the intraocular power calculation formula for children and
      the change of the refraction. SUBJECT AND METHODS: We reviewed the medical
      records of 66 pediatric cases with intraocular lens (IOL) implantation after
      cataract extraction and results of questionnaire of the Japanese Association of
      Pediatric Ophthalmology and Japanese Society of Cataract and Refractive Surgery.
      We employed four IOL power calculation formulae(SRK, SRK II, SRK/T, Holladay) to
      evaluate the accuracy of preoperative prediction of refraction. RESULTS: The best
      preoperative prediction was obtained by the SRK formula; the predictive
      refraction error within +/- 1 D was shown in 65% of patients. SRK/T and Holladay
      formulas were less accurate in patients aged 5 years old or younger. All formulae
      were less accurate in patients with axial length of 22 mm or shorter. There was
      no significant difference in the mean change in refraction over four years among
      three different age group (group 1: < = 5, group 2: 6 << = 10, group 3: 11 << =
      15(years old(YO)). However, several patients aged 10(YO) or younger showed severe
      myopic changes during this period. CONCLUSION: The IOL power calculation fomulae
      show less accuracy on pediatric cases. It is also difficult to predict the change
      of refraction on pediatric cases.

PMID- 12048923
TI  - [Reflexive and voluntary saccades in Parkinson's disease].
AB  - PURPOSE: To evaluate the characteristics of saccadic eye movements in patients
      with Parkinson's disease(PD). SUBJECTS AND METHODS: Eye movements of 14 patients
      with moderate to advanced PD and 12 age-matched controls were recorded with an
      infrared system. Two kinds of saccade tasks were used: saccade tasks for
      eliciting reflexive saccades(visually guided saccades in the gap condition) and
      saccade tasks for eliciting volitional saccades(visually guided saccades,
      saccades in overlap condition, memory-guided saccades, and anti-saccades).
      Latency, accuracy, peak velocity, and other parameters of saccades were
      evaluated. RESULTS: Visually guided saccades and saccades in the gap condition
      were slightly hypometric in PD patients. Saccades in the short-term overlap
      condition were not impaired in PD patients. Increased mean latencies and
      decreased degrees of accuracy of memory-guided saccades, and increased error
      rates of the memory-guided saccade task were marked in PD patients. Error rates
      in the anti-saccade task were not increased in PD but the mean saccadic latencies
      were slightly increased. CONCLUSION: Reflexive saccades are preserved in PD,
      whereas memory-guided saccades are markedly impaired. But anti-saccades in a task
      for eliciting in volitional saccades are not impaired in PD.

PMID- 12048925
TI  - [Clinical study on surgical outcome of penetrating keratoplasty for herpetic
      leukoma].
AB  - PURPOSE: To evaluate prognostic factors, rejection, and recurrence of herpetic
      keratitis, in keratoplasty for herpetic leukoma. SUBJECTS AND METHODS: We
      compared surgical outcome between patients who underwent keratoplasty for
      herpetic leukoma and those who received it for non-herpetic disorders. We
      compared the eyes of 24 patients in the herpetic group with 17 eyes of 20
      patients with non-herpetic corneal disorders, i.e., the non-herpetic group.
      RESULTS: The rejection rate was 45.8% for the herpetic group and 5.00% for the
      non-herpetic group, showing significant difference(p < 0.05). Transparent grafts
      were obtained for 75.0% of the herpetic group and 85.0% of the non-herpetic
      group, giving no significant difference. In the herpetic group, graft
      transparency in eyes with recurrences were 94.1%(p < 0.05). Graft rejection
      occurred mostly within 1 year postoperatively. RecuRrent herpetic keratitis
      tended to occur within 3 years and it was later than graft rejection. CONCLUSION:
      In patients who underwent keratoplasty for herpetic leukoma, steroid therapy is
      important for 1 postoperative year to suppress graft rejection, but after that,
      steroid treatment should be carefully considered to minimize the risk of
      recurrences of herpetic keratitis.

PMID- 12048924
TI  - [Measurement of flow velocity in feeder vessels of choroidal neovascularization
      with a scanning laser ophthalmoscope and image analysis system].
AB  - PURPOSE: To measure flow velocities in feeder vessels of choroidal
      neovascularization(CNV) secondary to age-related macular degeneration(AMD).
      METHODS: We examined early images of indocyanine green(ICG) angiography in 29
      eyes with CNV secondary to AMD, in which feeder vessels could be identified. ICG
      videoangiographic images recorded at 30 frames per second with a scanning laser
      ophthalmoscope were installed in a personal computer. With original software,
      optical density measurements made with an image analyzer were performed on ICG
      videoangiograms for determination of dye-dilution curves. The time(T50) from the
      beginning of a dye-dilution curve to the ascending parts of the curve at 50% of
      the peak intensity was calculated. Flow velocity in a feeder vessel was obtained
      by dividing the distance between two points by the circulation time between T50 s
      at the two points on the feeder vessel. RESULTS: The mean flow velocity in feeder
      vessels was 33.8 +/- 32.5 (mean +/- standard deviation) mm/sec. The mean velocity
      in the feeder vessels of large CNV with greatest linear diameter of 1 disc
      diameter(DD) or larger was 43.4 +/- 30.6 mm/sec; the mean velocity in the feeder
      vessels of small CNV with greatest linear diameter smaller than 1DD was 20.3 +/-
      20.2 mm/sec. There was a significant difference between them. CONCLUSION: The
      flow velocity in feeder vessels of CNV could be measured with ICG angiography and
      a computer-based image analysis system. This system would be useful in evaluation
      of choroidal circulation.

PMID- 12048926
TI  - [Vitrectomy for pseudophakic cystoid macular edema].
AB  - PURPOSE: To evaluate the effect of vitrectomy for pseudophakic cystoid macular
      edema(CME). PATIENTS AND METHODS: This study included 34 eyes of 31 patients that
      underwent vitrectomy for CME after intraocular lens(IOL) surgery without
      complications. CME was diagnosed by slit-lamp biomicroscopy with contact lens.
      Visual acuity and CME status were evaluated preoperatively and postoperatively.
      The interval between IOL surgery and vitrectomy was from 1 to 52 months, with an
      average of 11 months. Vitreous gel was beneath the iris in all cases, and there
      was no adhesion to the anterior segment. Preoperative visual acuity ranged from
      0.1 to 0.9, with an average of 0.44. RESULTS: CME was resolved postoperatively in
      all cases. Resolution period ranged from 1 to 12 months, with an average of 2.6
      months. Visual acuity improved postoperatively and ranged from 0.1 to 1.2, with
      an average of 0.84. The factors related to postoperative visual acuity were IOL
      CME interval, preoperative visual acuity, and the period of CME resolution. The
      factor related to the period of CME resolution was preoperative visual acuity.
      CONCLUSION: After vitrectomy for CME after IOL surgery without complications, CME
      resolves quickly and visual acuity improves. Early vitrectomy has good visual
      results.

PMID- 12048927
TI  - [A case of orbital myositis complicated with optic neuropathy--analysis of the
      pathological mechanism of optic neuropathy from magnetic resonance imaging
      findings].
AB  - BACKGROUND: We observed a rare case of orbital myositis involving the optic
      nerve. CASE: A 52-year-old woman complained of visual disturbance, lid swelling,
      ocular pain, and conjunctival injection in her right eye. Her corrected vision
      was 0.15 in the right eye and 1.2 in the left eye. Relative afferent pupillary
      defect(RAPD) and central scotoma in visual field test were noted in the right
      eye. Ocular movement of her right eye was moderately disturbed in all directions.
      Although laboratory data showed elevation of erythrocyte sedimentation rate,
      other hematological data such as thyroid function, autoimmune antibodies, and
      viral infection antibodies were normal. Magnetic resonance imaging(MRI) findings
      showed compression of the optic nerve at the orbital apex by marked thickening of
      the right lateral rectus muscle and superior rectus muscle, and inflammation
      directly invading the optic nerve. Based on the above findings, we diagnosed the
      case as orbital myositis complicated with optic neuropathy, and started
      corticosteroid therapy. Her right corrected vision improved dramatically, and the
      RAPD, central scotoma, and lid swelling disappeared shortly after administration.
      Enlargement of the extraocular muscles was still present one month after
      corticosteroid therapy. CONCLUSION: MRI findings suggested that optic neuropathy
      in this case was induced not only by mechanical compression by the enlarged
      extraocular muscles at the orbital apex but also by direct inflammatory
      infiltration from the extraocular muscles.

PMID- 12048928
TI  - [Animal paradigm of human cytomegalovirus retinitis].

PMID- 12048929
TI  - [Seminal lactate dehydrogenase C4 (LDH-C4) isozyme activity in infertile men].
AB  - Lactate dehydrogenase C4 (LDH-C4) is the specific isozyme of LDH produced by germ
      cells. We measured LDH-C4 activity in seminal plasma from infertile men with
      oligozoospermia or azoospermia using gel electrophoresis. Total LDH activity in
      seminal plasma from infertile patients (n = 99) was 2,487 +/- 1,384 IU/l (mean +/
      SD). LDH-C4 isozyme activity was detected in 63 out of 75 seminal plasma samples
      from infertile patients with a mean of 383 +/- 356 IU/l (13.8 +/- 8.6% of total
      LDH). Sperm count was positively correlated with LDH-C4 (r = 0.298; P < 0.05),
      but not with any other LDH isozymes or with total LDH. Seminal LDH-C4 was
      significantly lower in patients with varicoceles (253 +/- 223 IU/l) than without
      varicoceles (474 +/- 262 IU/l). Six azoospermia patients were treated with hCG
      and hMG. Three out of four patients whose seminal plasma revealed LDH-C4 activity
      responded to the treatment, whereas none of the other two patients without
      seminal LDH-C4 activity did. These results indicate the clinical usefulness of
      seminal LDH-C4 as a potential marker for seminal epithelium activity in the
      diagnosis and treatment of male infertility.

PMID- 12048930
TI  - [Subsequent upper urothelial cancer following bladder tumor].
AB  - A total of 110 patients were treated with primary transitional cell carcinoma
      (TCC) of the urinary bladder from 1990 to 2000. During the follow-up period,
      which was for at least two years, four patients (3.6 percent) had subsequent
      upper urothelial cancer at an average of 61.5 months after initial treatment of
      the bladder tumor. Two of the four patients received transurethral resection
      several times, and the remaining two patients underwent radical cystectomy for
      the initial bladder tumor. The histopathological findings of subsequent upper
      urothelial cancer were almost the same as those for the initial bladder tumor.
      One patient had accompanying carcinoma in situ (CIS) and the other had
      adenocarcinoma with TCC. Since 1) high grade, 2) multiple, 3) recurrent and 4)
      occupational bladder tumors, 5) concomitant CIS, 6) vesicoureteral reflux and 7)
      tumor invasion of the intravesical ureters have been reported to be risk factors
      for developing subsequent upper urothelial cancer, patients with bladder tumors
      who have these risk factors should be followed-up closely.

PMID- 12048931
TI  - [Comparison of laparoscopic versus open surgery for adrenal tumor].
AB  - We performed 25 laparoscopic adrenalectomies for adrenal tumor between January
      1998 and December 2000. In 23 cases, adrenal tumors were successfully removed
      laparoscopically, but in 2, the laparoscopic procedure was converted to open
      surgery because of liver injury and endoscopically uncontrolled bleeding at the
      renal hilum. Postoperative complications, involving retroperitoneal hematoma,
      hypercapnia, and wound infections, could be managed without surgical treatment.
      We compared laparoscopic adrenalectomy with conventional open surgery, which had
      been performed for 24 adrenal tumors in our clinic. The mean operative time for
      the laparoscopic adrenalectomy (228.8 +/- 65.5 minutes) was significantly longer
      than those for the open surgery (156.0 +/- 43.8 minutes). The estimated blood
      loss (82.3 +/- 125.4 g) was significantly less than those for the open surgery
      (210.8 +/- 167.7 g), and the laparoscopic adrenalectomy had significant
      advantages in lessening postoperative analgesic requirements, shortening
      postoperative recovery period, and preserving good physical appearance.
      Therefore, we conclude that the laparoscopic adrenalectomy is a less invasive
      surgery, and is acceptable as a standard operation for adrenal tumors.

PMID- 12048932
TI  - [A low-fat and high soybean protein diet for patients with elevated serum PSA
      level: alteration of QOL and serum PSA level after the dietary intervention].
AB  - Considerable epidemiological evidence has indicated a relationship between diet
      and prostate cancer. Many studies have shown positive associations between
      dietary fat and prostate cancer, and inverse associations with soybean intake. To
      prevent prostate cancer, we have tried dietary intervention for patients showing
      an elevated prostate specific antigen (PSA) level. A total of 96 patients who did
      not show any evidence of prostate cancer by transrectal ultrasonography and/or
      prostate biopsy despite high serum PSA level were placed on a supervised dietary
      intervention program consisting of a low fat and high soybean protein diet. The
      primary endpoint was the alteration of quality of life (QOL) and PSA after 3
      months of intervention. Response to the questionnaire indicated that 88% of the
      patients desired to join such a study, and that 90% of the patients continued the
      dietary control after 3 months of supervision. About 60% patients adhered
      strictly to the dietary menus, and 90% of the subject planed to continue. Less
      than 20% of the patients complained of deterioration of dietary QOL. The average
      serum PSA level decreased from 6.9 ng/ml to 5.6 ng/ml after 3 months, which was
      statistically significant (p = 0.01). This dietary intervention almost maintains
      the patient's QOL, decreases the serum PSA level, and indicates the possibility
      of prevention of prostate cancer by dietary intervention.

PMID- 12048933
TI  - [A clinical study on tumor-associated monocyte lineage cells in renal cell
      carcinoma].
AB  - To investigate the relationship between the ratio of monocytes infiltrating renal
      cell carcinoma (RCC) and prognosis, in 78 patients who underwent nephrectomy, the
      positive rate of the following parameters was assessed immunohistochemically
      under light microscopy: tumor-associated macrophage (TAM), microvessel density
      (MVD), S-100 cell, HLA-DR cell, apoptosis index (AI) and proliferative index
      (PI). The relationship between the positive rate of these parameters and
      prognosis, and intercorrelations among these parameters were analyzed. A positive
      correlation with prognosis was observed in patients positive for TAM, MVD or PI
      (r = 0.625). Prognosis was poor for patients with high levels of these
      parameters. Furthermore, the number of S-100-positive cells was a prognostic
      factor only in patients with metastatic RCC. Although the role of TAM as a
      prognostic factor in RCC is clear, no linear relationship was identified between
      prognosis and other monocytes.

PMID- 12048934
TI  - Encrusted cystitis with ammonium acid urate calculi: a case report.
AB  - We present a case of encrusted cystitis with ammonium acid urate calculi. An 88
      year-old man was referred to our hospital to determine the cause of hematopyuria.
      He was a patient at another hospital for treatment of interstitial pneumonia with
      predonisolone. After admission to our hospital, kidney, ureter, bladder X-ray,
      computed togography and cystoscopy revealed calcification of about two-thirds of
      the mucosa of the bladder, and biopsy of the bladder revealed bacterial colonies
      with inflammation and calcification. Calculographic analysis revealed ammonium
      acid urate calculi. After treatment with antibiotics and irrigation with solita
      T1, an acidic solution of pH 3.5-6.5, inflammation and calcification were
      significantly reduced.

PMID- 12048935
TI  - [A case of leiomyosarcoma of the spermatic cord].
AB  - A 44-year-old male was referred to our hospital for further treatment of lung and
      adrenal metastases from leiomyosarcoma occurring in the left spermatic cord. He
      had undergone high orchiectomy 5 months before, but no adjuvant therapy was done.
      Although systemic CYVADIC therapy (cyclophosphamide, vincristine, doxorubicin
      hydrochloride, dacarbazine) was performed in our hospital, he died of metastatic
      disease 10 months after the initial therapy. Leiomyosarcoma arising in the
      spermatic cord is a rare entity. We present a case of leiomyosarcoma of the
      spermatic cord, and to our knowledge, this is the 23rd case reported in Japan.

PMID- 12048936
TI  - [A case of foreign body in the urinary bladder--chewing gum found in urinary
      bladder].
AB  - We experienced a case of a 60-year-old male with a foreign body in the urinary
      bladder. He had inserted chewing gum into the urethra for the purpose of
      masturbation, and it had slipped into the bladder. We collected 1,436 cases of
      vesico-urethral foreign body from the Japanese literature including our case, and
      reviewed these cases with some statistical analysis.

PMID- 12048937
TI  - [A case of urolithiasis due to vitamin D intoxication in a patient with
      idiopathic hypoparathyroidism].
AB  - We report a case of urolithiasis in a patient with idiopathic hypoparathyroidism
      treated with vitamin D therapy. A 30-year-old woman with idiopathic
      hypoparathyroidism, who had been treated with vitamin D therapy with 2-4
      micrograms/day of alpha-calcidol for 9 years, was admitted for recurrence of
      bilateral renal stones and progressing left hydronephrosis. Laboratory data
      revealed normal serum calcium level and remarkable hypercalciuria. The dose of
      oral administration of alpha-calcidol was reduced to 1 microgram/day and 2 mg/day
      of trichlormethiazide was started. Now her serum calcium concentration and the
      total amount of urine calcium was completely under control. Bilateral renal
      stones are no longer progressive and tetany has not been recognized. We
      considered it essential to monitor closely not only the serum but also the urine
      calcium level in the vitamin D therapy for idiopathic hypoparathyroidism.

PMID- 12048938
TI  - [A case of adenocarcinoma arising in female urethral diverticulum].
AB  - An 81-year-old woman was admitted with a chief complaint of bloody discharge from
      the urethra. On physical examination an elastic-soft mass was palpable beneath
      the anterior vaginal wall. Magnetic resonance imaging and computed tomographic
      scan revealed the mass around the urethra. Transvaginal needle biopsy was
      performed and the histopathologic finding was adenocarcinoma. The tumor was
      excised with the uterus, the ovary and the anterior vaginal wall. The macroscopic
      appearance suggested that the tumor arose in the urethral diverticulum. She had
      intravesical recurrence at 8 months after the operation, and partial cystectomy
      was performed. However there was recurrence again, and radical cystectomy was
      performed finally. We review 81 cases of urethral diverticular carcinoma in the
      literature.

PMID- 12048939
TI  - [Synchronous triple urogenital cancer (renal cancer, bladder cancer, prostatic
      cancer): a case report].
AB  - A case of synchronous triple urogenital cancer, which was comprised of renal cell
      carcinoma of the left kidney, transitional cell carcinoma of the urinary bladder,
      and adenocarcinoma of the prostate, is reported. A 72-year-old Japanese male
      patient was referred to our outpatient clinic with the complaint of asymptomatic
      hematuria. At that time, his serum of level of PSA was elevated to 20 ng/ml.
      Cystourethroscopy showed a papillary bladder tumor and coagula through the left
      urinary orifice. Ultrasonography, computed tomography and magnetic resonance
      imaging showed a mass lesion measuring about 6 cm by 5 cm in the left kidney.
      Angiography showed a hypervascular lesion measuring about 6 cm by 5 cm at the
      same site. Double cancer, consisting of renal cell carcinoma and transitional
      cell carcinoma of the urinary bladder, was suspected and we performed left total
      nephroureterectomy, hilar lymphadenectomy, and transurethral rection of the
      bladder tumor, one month later. At the same time, we performed a biopsy of the
      prostate. Histological diagnosis was renal cell carcinoma, clear cell carcinoma
      and transitional cell carcinoma of urinary bladder. Histological diagnosis of the
      prostate biopsy was moderately differentiated adenocarcinoma. Since this case
      fulfilled the criteria of Warren and Gates, it was classified as synchronous
      triple urogenital cancer. A review of the literature revealed 17 authentic cases
      of triple urogenital cancer, of which 14 and 10 cases were reported as a
      combination of renal cancer, bladder cancer and prostatic cancer, in the world
      and in Japan, respectively. Furthermore, he had been exposed to the atomic bomb
      explosion in Hiroshima in 1945. This carcinogenic precursor may be related to the
      development of the triple cancer.

PMID- 12048940
TI  - [Four cases of spontaneous rupture of the urinary bladder].
AB  - Between November 1997 and March 2001, 4 female patients from 44 to 65 years of
      age with a spontaneous rupture of the urinary bladder were analyzed. They
      complained of abdominal pain and had undergone an intra-pelvic gynecological
      operation (3 for uterine cancer, 1 for an ovarian cyst) several years before. The
      three with uterine cancer had also received radiation therapy. For their present
      condition, spontaneous urinary bladder rupture, their treatment was indwelling a
      urethral catheter. Two of them have had no recurrence of urinary bladder rupture
      after one month since having the urethral catheter indwelt. One, however, had to
      have the catheter re-indwelt due to unsuccessful suturing of the urinary bladder
      wall. The fourth patient had bilateral nephrostomy tubes due to severe radiation
      cystitis. Thus, one can infer that intra-pelvic gynecological operations and
      radiation therapy are major factors causing spontaneous urinary bladder rupture.
      While indwelling a urethral catheter may be effective for some patients with a
      spontaneous rupture of the urinary bladder, it may be very difficult to treat
      more complicated cases.

PMID- 12048941
TI  - [A case of complete self-mutilation of penis].
AB  - Self-mutilation of the penis is extremely rare. A 69-year-old man was admitted
      after having amputated his own penis completely from its root. He had no history
      of psychiatric illness, but his physical condition on admission was abnormal. We
      performed urethrocutaneostomy, rather than replantation of the penis, because of
      the danger that he would reinjure himself. The patient was treated by a
      psychiatrist under a diagnosis of alcoholic dementia. To our knowledge, this is
      the 24th case of self-mutilation of the penis reported in the Japanese
      literature.

PMID- 12048942
TI  - Perceptual-cognitive universals as reflections of the world.
AB  - The universality, invariance, and elegance of principles governing the universe
      may be reflected in principles of the minds that have evolved in that universe-
      provided that the mental principles are formulated with respect to the abstract
      spaces appropriate for the representation of biologically significant objects and
      their properties. (1) Positions and motions of objects conserve their shapes in
      the geometrically fullest and simplest way when represented as points and
      connecting geodesic paths in the six-dimensional manifold jointly determined by
      the Euclidean group of three-dimensional space and the symmetry group of each
      object. (2) Colors of objects attain constancy when represented as points in a
      three-dimensional vector space in which each variation in natural illumination is
      canceled by application of its inverse from the three-dimensional linear group of
      terrestrial transformations of the invariant solar source. (3) Kinds of objects
      support optimal generalization and categorization when represented, in an
      evolutionarily-shaped space of possible objects, as connected regions with
      associated weights determined by Bayesian revision of maximum-entropy priors.

PMID- 12048943
TI  - The exploitation of regularities in the environment by the brain.
AB  - Statistical regularities of the environment are important for learning, memory,
      intelligence, inductive inference, and in fact, for any area of cognitive science
      where an information-processing brain promotes survival by exploiting them. This
      has been recognised by many of those interested in cognitive function, starting
      with Helmholtz, Mach, and Pearson, and continuing through Craik, Tolman,
      Attneave, and Brunswik. In the current era, many of us have begun to show how
      neural mechanisms exploit the regular statistical properties of natural images.
      Shepard proposed that the apparent trajectory of an object when seen successively
      at two positions results from internalising the rules of kinematic geometry, and
      although kinematic geometry is not statistical in nature, this is clearly a
      related idea. Here it is argued that Shepard's term, "internalisation," is
      insufficient because it is also necessary to derive an advantage from the
      process. Having mechanisms selectively sensitive to the spatio-temporal patterns
      of excitation commonly experienced when viewing moving objects would facilitate
      the detection, interpolation, and extrapolation of such motions, and might
      explain the twisting motions that are experienced. Although Shepard's explanation
      in terms of Chasles' rule seems doubtful, his theory and experiments illustrate
      that local twisting motions are needed for the analysis of moving objects and
      provoke thoughts about how they might be detected.

PMID- 12048944
TI  - Regularities of the physical world and the absence of their internalization.
AB  - The notion of internalization put forth by Roger Shepard continues to be
      appealing and challenging. He suggests that we have internalized, during our
      evolutionary development, environmental regularities, or constraints.
      Internalization solves one of the hardest problems of perceptual psychology: the
      underspecification problem. That is the problem of how well-defined perceptual
      experience is generated from the often ambiguous and incomplete sensory
      stimulation. Yet, the notion of internalization creates new problems that may
      outweigh the solution of the underspecification problem. To support this claim, I
      first examine the concept of internalization, breaking it down into several
      distinct interpretations. These range from well-resolved dynamic regularities to
      ill-resolved statistical regularities. As a function of the interpretation the
      researcher selects, an empirical test of the internalization hypothesis may be
      straightforward or it may become virtually impossible. I then attempt to cover
      the range of interpretations by drawing on examples from different domains of
      visual event perception. Unfortunately, the experimental tests regarding most
      candidate regularities, such as gravitational acceleration, fail to support the
      concept of internalization. This suggests that narrow interpretations of the
      concept should be given up in favor of more abstract interpretations. However,
      the latter are not easily amenable to empirical testing. There is nonetheless a
      way to test these abstract interpretations by contrasting internalization with
      the opposite concept: externalization of body dynamics. I summarize evidence for
      such a projection of body constraints onto external objects. Based on the
      combined evidence of well-resolved and ill-resolved regularities, the value of
      the notion of internalization has to be reassessed.

PMID- 12048945
TI  - Internalization: a metaphor we can live without.
AB  - Shepard has supposed that the mind is stocked with innate knowledge of the world
      and that this knowledge figures prominently in the way we see the world.
      According to him, this internal knowledge is the legacy of a process of
      internalization; a process of natural selection over the evolutionary history of
      the species. Shepard has developed his proposal most fully in his analysis of the
      relation between kinematic geometry and the shape of the motion path in apparent
      motion displays. We argue that Shepard has made a case for applying the
      principles of kinematic geometry to the perception of motion, but that he has not
      made the case for injecting these principles into the mind of the percipient. We
      offer a more modest interpretation of his important findings: that kinematic
      geometry may be a model of apparent motion. Inasmuch as our recommended
      interpretation does not lodge geometry in the mind of the percipient, the
      motivation of positing internalization, a process that moves kinematic geometry
      into the mind, is obviated. In our conclusion, we suggest that cognitive
      psychologists, in their embrace of internal mental universals and internalization
      may have been seduced by the siren call of metaphor.

PMID- 12048946
TI  - Evolutionary internalized regularities.
AB  - Roger Shepard's proposals and supporting experiments concerning evolutionary
      internalized regularities have been very influential in the study of vision and
      in other areas of psychology and cognitive science. This paper examines issues
      concerning the need, nature, explanatory role, and justification for postulating
      such internalized constraints. In particular, I seek further clarification from
      Shepard on how best to understand his claim that principles of kinematic geometry
      underlie phenomena of motion perception. My primary focus is on the ecological
      validity of Shepard's kinematic constraint in the context of ordinary motion
      perception. First, I explore the analogy Shepard draws between internalized
      circadian rhythms and the supposed internalization of kinematic geometry. Next,
      questions are raised about how to interpret and justify applying results from his
      own and others' experimental studies of apparent motion to more everyday cases of
      motion perception in richer environments. Finally, some difficulties with
      Shepard's account of the evolutionary development of his kinematic constraint are
      considered.

PMID- 12048947
TI  - Generalization, similarity, and Bayesian inference.
AB  - Shepard has argued that a universal law should govern generalization across
      different domains of perception and cognition, as well as across organisms from
      different species or even different planets. Starting with some basic assumptions
      about natural kinds, he derived an exponential decay function as the form of the
      universal generalization gradient, which accords strikingly well with a wide
      range of empirical data. However, his original formulation applied only to the
      ideal case of generalization from a single encountered stimulus to a single novel
      stimulus, and for stimuli that can be represented as points in a continuous
      metric psychological space. Here we recast Shepard's theory in a more general
      Bayesian framework and show how this naturally extends his approach to the more
      realistic situation of generalizing from multiple consequential stimuli with
      arbitrary representational structure. Our framework also subsumes a version of
      Tversky's set-theoretic model of similarity, which is conventionally thought of
      as the primary alternative to Shepard's continuous metric space model of
      similarity and generalization. This unification allows us not only to draw deep
      parallels between the set-theoretic and spatial approaches, but also to
      significantly advance the explanatory power of set-theoretic models.

PMID- 12048948
TI  - Is kinematic geometry an internalized regularity?
AB  - A general framework for the explanation of perceptual phenomena as
      internalizations of external regularities was developed by R. N. Shepard. A
      particular example of this framework is his account of perceived curvilinear
      apparent motions. This paper contains a brief summary of the relevant
      psychophysical data, some basic kinematical considerations and examples, and
      several criticisms of Shepard's account. The criticisms concern the feasibility
      of internalization of critical motion types, the roles of simplicity and
      uniqueness, the contrast between classical physics and kinematic geometry, the
      import of perceived path curvilinearity, and the relation of perceptual and
      scientific knowledge.

PMID- 12048949
TI  - War, peace, and fertility in Angola.
AB  - Using data from a nationally representative survey conducted in 1996, some two
      years after the end of a major outbreak of war, we examine the impact of war on
      the timing of recent births and war-related differences in reproductive
      preferences in Angola. We find evidence of a wartime drop and a postwar rebound
      in fertility, but these trends vary greatly, depending on the type and degree of
      exposure to war and on women's socioeconomic characteristics. At the same time,
      variations by parity are nonsignificant. In fertility preferences, the relative
      antinatalism of Angola's most modernized urban area stands out, but outside this
      area, differences between areas that were more and less affected by war are also
      noticeable. We offer interpretations of our findings and outline their
      implications for Angola's demographic future and demographic trends in similar
      settings.

PMID- 12048950
TI  - Education and fertility in sub-Saharan Africa: individual and community effects.
AB  - Using data from Demographic and Health Surveys for 22 countries in Sub-Saharan
      Africa, I show that the average educational level in a village or a community of
      a similar size has a significant depressing effect on a woman's birth rates, net
      of urbanization and her own education. According to simulations, average
      fertility for these countries would be 1.00 lower if education were expanded from
      the current level in the region to the relatively high level in Kenya. The
      exclusion of aggregate education from the model leaves a response of only 0.52. A
      considerable aggregate contribution is estimated even when several potential
      determinants of education are included. This finding illustrates the need to
      consider aggregate education in future assessments of the total impact of
      education.

PMID- 12048951
TI  - Spatial variation in contraceptive use in Bangladesh: looking beyond the borders.
AB  - This article promotes a more complete understanding of social change by analyzing
      spatial patterns of contraceptive use in Bangladesh and the contiguous state of
      West Bengal in India. Multilevel analyses that control for variations in
      individual- and household-level correlates show an important role for cross
      border influences only in those districts that share a common language across the
      border. The districts that are positive outliers in contraception hug the
      Bangladesh-West Bengal border. A map of outliers shows that the positive outliers
      form a contiguous band in a manner suggestive of a role for contagion.

PMID- 12048952
TI  - Adjusting period tempo changes with an extension of Ryder's basic translation
      equation.
AB  - We show that the observed changes in the period tempo of fertility are biased and
      derive a new formula for adjusting such bias. We present illustrative
      applications of our proposed method to the cases of the United States and Taiwan.
      We then describe the relevance of adjustments of observed period fertility tempo
      for evaluating family planning programs aiming at delaying and reducing births to
      slow down population growth in developing countries. The work reported in this
      article also can be regarded as an extension of Ryder's basic translation
      equation. The extension provides a set of formulas expressing relationships of
      quantum-tempo between cohorts and periods under specified assumptions.

PMID- 12048953
TI  - A simple method for estimating age-specific rates from sequential cross sections.
AB  - I develop and demonstrate a simple formula for estimating age-specific event
      rates for a period from "before" and "after" cross sections. The general approach
      applies to a wide range of estimation problems in demography, the social
      sciences, and epidemiology. The method arises from the formal mathematics of
      unstable populations and is similar in spirit to "variable-r" methods. Unlike
      those methods, however, the new technique does not require specialized computer
      programming or iterative calculations, and event rates can be calculated directly
      from cross-sectional data in simple spreadsheets. The article includes a formal
      mathematical exposition of the method, simulation tests, and several examples.

PMID- 12048954
TI  - Nonmarital childbearing: influences of education, marriage, and fertility.
AB  - We examined the determinants of nonmarital fertility, focusing on the effects of
      other life-course events: education, marriage, marital dissolution, and marital
      fertility. Since these determinants are potentially endogenous, we modeled the
      processes that generate them jointly with nonmarital fertility and accounted for
      the sequencing of events and the unobserved correlations across processes. The
      results showed that the risk of nonmarital conception increases immediately after
      leaving school and that the educational effects are less pronounced for black
      women than for other women. The risk is lower for previously married women than
      for never-married women, even controlling for age, but this reduction is
      significant only for black women. The more children a woman already has, the
      lower her risk of nonmarital childbearing, particularly if the earlier children
      were born during a previous marriage. Ignoring endogeneity issues seriously
      biases the estimates of several substantively important effects.

PMID- 12048955
TI  - Stability across cohorts in divorce risk factors.
AB  - Over the past quarter-century, many covariates of divorce have been identified.
      However, the extent to which the effects of these covariates remain constant
      across time is not known. In this article, I examine the stability of the effects
      of a wide range of divorce covariates using a pooled sample of data taken from
      five rounds of the National Survey of Family Growth. This sample includes
      consistent measures of important predictors of divorce, covers marriages formed
      over 35 years (1950-1984), and spans substantial historical variation in the
      overall risk of marital dissolution. For the most part, the effects of the major
      sociodemographic predictors of divorce do not vary by historical period. The one
      exception is race. These results suggest that the effects associated with
      historical period have been pervasive, simultaneously altering the risk of
      divorce for most marriages.

PMID- 12048956
TI  - Low birth weight, social factors, and developmental outcomes among children in
      the United States.
AB  - We used six waves of the National Longitudinal Survey of Youth-Child Data (1986
      1996) to assess the relative impact of adverse birth outcomes vis-a-vis social
      risk factors on children's developmental outcomes. Using the Peabody Individual
      Achievement Tests of Mathematics and Reading Recognition as our outcome
      variables, we also evaluated the dynamic nature of biological and social risk
      factors from ages 6 to 14. We found the following: (1) birth weight is
      significantly related to developmental outcomes, net of important social and
      economic controls; (2) the effect associated with adverse birth outcomes is
      significantly more pronounced at very low birth weights (< 1,500 grams) than at
      moderately low birth weights (1,500-2,499 grams); (3) whereas the relative effect
      of very low-birth-weight status is large, the effect of moderately low weight
      status, when compared with race/ethnicity and mother's education, is small; and
      (4) the observed differentials between moderately low-birth-weight and normal
      birth-weight children are substantially smaller among older children in
      comparison with younger children.

PMID- 12048957
TI  - The effects of early maternal employment on child cognitive development.
AB  - We investigated the effects of early maternal employment on children's cognitive
      outcomes, using data from the National Longitudinal Survey of Youth on 1,872
      children who can be followed from birth to age 7 or 8. We found some persistent
      adverse effects of first-year maternal employment and some positive effects of
      second- and third-year maternal employment on cognitive outcomes for non-Hispanic
      white children, but not for African American or Hispanic children. These effects
      are present even after we controlled for a range of individual and family
      characteristics that affect child development, including those that are likely to
      be correlated with maternal employment, such as breast-feeding and the use of
      nonmaternal child care. Controlling for family fixed effects reduces the effects
      of early maternal employment on some cognitive outcomes but not on others.

PMID- 12048958
TI  - Good things come in threes: single-parent multigenerational family structure and
      adolescent adjustment.
AB  - Using data from the National Educational Longitudinal Study (NELS), we found that
      teenagers who live in nonmarried families are less likely to graduate from high
      school or to attend college, more likely to smoke or drink, and more likely to
      initiate sexual activity. Not all nonmarried families are alike, however. In
      particular, teenagers living with their single mothers and with at least one
      grandparent in multigenerational households have developmental outcomes that are
      at least as good and often better than the outcomes of teenagers in married
      families. These findings obtain when a wide array of economic resources,
      parenting behavior, and home and school characteristics are controlled for.

PMID- 12048959
TI  - Can J & J keep the magic going?

PMID- 12048960
TI  - Why companies fail.

PMID- 12048961
TI  - Learning while black.

PMID- 12048962
TI  - Meet the beetles.

PMID- 12048963
TI  - Making a Priest pay.

PMID- 12048964
TI  - An ounce of prevention.

PMID- 12048965
TI  - Testing of the PHS-ES: a measure of Perimenopausal Health Self-Efficacy.
AB  - This article summarizes the development and psychometric analysis of the
      Perimenopausal Health Self-Efficacy Scale (PHS-ES) designed to assess women's
      health promotion self-efficacy related to mid-life changes in health. Items were
      generated from a qualitative study of HRT decision-making and recommended health
      promotion activities. The PHS-ES was administered 2 weeks apart to 98 university
      based women ages 45 to 64 along with the measures of functional health status,
      stress, and the self-concept. Internal consistency (alpha = .88 and .90) and test
      retest reliabilities (.86) were acceptable. Four factors emerged during factor
      analysis with 21 of the items explaining 50% of the variance and which were
      consistent with the conceptual basis of the PHS-ES. The PHS-ES was significantly
      correlated with functional health status, self-concept, stress, age and body mass
      index (BMI). In conjunction with stress and BMI, the PHS-ES predicted 50% of the
      variance of functional health. Further reliability and validity assessments are
      recommended with more racially and socioeconomically heterogeneous groups of
      perimenopausal women. It was concluded that the PHS-ES adequately demonstrated
      reliability and validity in this study.

PMID- 12048966
TI  - Correlations among measures of bladder function and comfort.
AB  - There is a need for standard functional and psychosocial measurements of
      compromised urinary bladder syndrome (CUBS). Utilizing Kolcaba's Comfort Theory,
      the purpose of this study was to assess the psychometric properties and
      relationships among 8 measures of comfort, status of urinary frequency and
      incontinence, and quality of life. A convenience sample of 47 persons (45 women,
      2 men) ages 25 to 92, who had UI for more than 6 months, was recruited. Data were
      collected twice with a 2-week interval. We examined (a) 1 measure of the
      immediate outcome of comfort related to CUBS, (b) 5 measures of UI status, and
      (c) 2 measures of quality of life. Reliabilities were adequate for all measures.
      Relationships among variables are presented and discussed. Recommendations are
      made for measures that detect improvement over time related to first line
      interventions.

PMID- 12048967
TI  - Item response theory in affective instrument development: an illustration.

PMID- 12048968
TI  - Stability of self-reported family history of prostate cancer among African
      American men.
AB  - The genome-wide search for the prostate cancer gene holds the promise of the
      availability of prostate cancer susceptibility testing in the near future. When
      this occurs, self-reported history of prostate cancer will be critical in
      determining who is eligible for cancer susceptibility testing. Little attention
      has been given to the reliability of self-reported family history of prostate
      cancer, particularly in African American men. This correlational study measured
      the stability of self-reported family history of prostate cancer over a one-year
      time period (between 1997 and 1998) with 96 African American men from a southern
      state. The men were asked on two separate occasions, 1 year apart, "Have any of
      your men blood relatives ever had prostate cancer?" The question had a prior test
      retest reliability of 0.85 over a 2-week period. Forty-eight percent of the men
      changed their answers on the second administration. Men most likely to change
      their answers were low-income men and men who did not participate in a free
      prostate cancer screening. This research highlights the need for public genetic
      education and the recognition by health professionals that self-reported family
      history of cancer is a variable that changes as families have increased awareness
      and communication concerning family history of cancer.

PMID- 12048969
TI  - A theoretical approach to measuring quality of life.
AB  - The purpose of this article is to discuss conceptual issues surrounding health
      related quality of life (HRQOL) and to provide an example of how structural
      equation modeling can address some of these conceptual issues. This article
      reports the development of the measurement model for overall quality of life, a
      dimension of HRQOL as conceptualized by Wilson and Cleary (1995). The sample (N =
      1410) is from the AIDS Time-Oriented Health Outcome Study (ATHOS) databank, a
      longitudinal observational database of persons with HIV-associated illness. The
      hypothesized second-order factor model consists of 5 latent variables and 17
      measured items. The fit indicators (RMSEA = .0717; SRMR = .0450; CFI = .951)
      suggest that the model provides an adequate description of the pattern of
      relationships in the data. A theoretical approach to HRQOL will expand its
      clinical use as an outcome measure and increase its relevance.

PMID- 12048970
TI  - A comparison of pain measures used with patients with fibromyalgia.
AB  - The objective of the present study was to evaluate instruments used to assess
      pain in patients with fibromyalgia (FMS). Participants were 602 patients with
      FMS. Pain was measured with five scales: a visual analog scale (VAS), the Pain
      Rating, Present Pain, and Number of Words Chosen Indexes from the McGill Pain
      Questionnaire; and intensity of pain obtained from a manual tender point exam.
      The VAS had the highest correlations with other measures of pain and with self
      efficacy for pain, physical functioning, fatigue, and stiffness. The correlations
      between the VAS and fatigue and stiffness were significantly higher than those of
      other pain measures (p < .01). Our findings suggest that the easy-to-administer
      VAS may be the most useful measure of pain with patients with FMS.

PMID- 12048971
TI  - Instrument translation and evaluation of equivalence and psychometric properties:
      the Chinese Sense of Coherence Scale.
AB  - Translating well-established English instruments into target languages other than
      English and testing cross-cultural validity to prove that the same attributes are
      being measured in each cultural group or country are required before a
      multicultural or international study can be conducted and cross-cultural
      comparisons of study results can be applied. However, rigorous and systematic
      cross-cultural efforts to test the effectiveness of specific translation methods
      are rare. This article presents a model of translation processes and empirical
      validation of the translated instrument through description of the translation of
      a selected instrument--the Sense of Coherence (SOC) Scale--from English into
      Chinese. A cyclic process of forward translations, back translations, and expert
      evaluation of equivalence by bilingual and English speaking experts was conducted
      to achieve conceptual equivalence between the original and translated
      instruments. Empirical validation of the Chinese SOC scale data from a group of
      bilingual Chinese people demonstrated non-identical, but comparable, item and
      scale means and variances, internal consistency, and relationships to an external
      criterion. Advantages and difficulties of using multi-rounds, multi-experts, and
      multi-methods to establish translation equivalence and to validate the translated
      Chinese SOC scale are discussed.

PMID- 12048972
TI  - [Consumption of home enteral nutrition products in the Autonomous Community of
      Madrid].
AB  - The purpose of the present paper is to identify the changes in the consumption of
      home enteral nutrition products paid for by the National Health System in the
      light of the amendments to the regulations governing this service within the
      scope of the Madrid Regional Community. To this end, the official Social Security
      forms prescribing these products have been studied for the months of October,
      1998, May, 1999, and May, 2000. These have been classified by brand names the
      number of units and cost have been tabulated. With the data obtained from this
      analysis, progress has been studied in terms of the following points: type of
      product, number of units, cost of each and share of consumption by manufacturers.
      The conclusion that can be drawn from the results obtained is that, since the
      start of the trend for increased consumption of this kind of product in November,
      1998, this trend has continued upwards both in terms of the number of units and
      their cost. Greater diversification can be seen in the products used, with a
      reduction in the prescription of those items which were financed almost
      exclusively by the system prior to the change in the regulations, and this has to
      some extent constrained the displacement of consumption towards the different
      distribution brands and considerably increasing the consumption of those products
      considered more specific and therefore with a higher mean cost. Furthermore, as
      these products are covered by the Spanish Defence of Competition Act, in other
      words, the market price is not restricted, there are significant differences in
      the prices invoiced for the same product depending on the pharmacy outlet
      dispensing it.

PMID- 12048973
TI  - [Bibliometric analysis of Nutricion Hospitalaria I].

PMID- 12048974
TI  - [Etiopathogenic factors in colorectal cancer. Genetic and clinical features
      (first of 2 parts)].
AB  - INTRODUCTION: Colorectal Cancer (CRC) is the second cause of death in Spain,
      reaching the first place in non-smoking population. It is also the tumour with
      the greatest one-year incidence. The last few years some reduction in its
      incidence along with a greater 5-year average survival has been observed.
      PATHOGENESIS: Most CRCs develop from benign polyps. Vogelstein's hypothesis
      suggests an orderly progression from normal mucosa, to a small polyp, to a large
      polyp and finally to a CRC. In this progression transforming cells will be
      increasingly charged with molecular alterations. GENETIC FACTORS: 20% of CRCs
      have a genetic background although only a fourth of these are genetically based.
      The APC (or FAP) gene mutation is one of the earlier events that can be seen in
      tumour progression. When this mutation appears in the germ line it renders
      Familial Adenomatose Polyposis Syndrome (that evolves to CRC in a 100% of cases)
      or to the Gardner Syndrome (if it has extracolonic expressions). The p53 mutation
      is a late event in cellular transformation but it makes a rapid accumulation of
      mutations an easier process and it confers advantages for survival of the tumour
      cells. Mutations in the genes implicated in microsatellite instability are
      related to DNA error repair; their clinical correlates are the Lynch I and II
      syndromes. Other important genes related to CRC are DCC and ras. CLINICAL
      FACTORS: Inflammatory Bowel Disease (particularly Crohn's disease) is the most
      important clinical factor, it may enhance basal risk 30 times. Other risk factors
      are: previous malignant conditions, pelvic irradiation and previous surgery
      (cholecystectomy and ureterosigmoidostomy). The endocrinologic factors have a
      rising importance and so hormonal substitution therapy for menopause and
      multiparity can provide some protection. The use of NSAIDs can also be protective
      (specially COX-2 inhibitors). CONCLUSIONS: It is important that people who are
      identified as having a high risk for developing a CRC are subjected to a strict
      clinical and endoscopic follow-up in order to be able to identify an incipient
      tumour or to practice prophylactic surgery. The use of hormonal substitution
      therapy or anti COX-2 NSAIDs can be future useful chemoprophylactic agents.

PMID- 12048975
TI  - [Evaluation of Hospital Nutrition IV: diffusion and visibility].
AB  - To conclude the bibliometric analysis of Nutricion Hospitalaria, we present here
      the data corresponding to the diffusion and visibility of the publication in the
      scientific sphere.

PMID- 12048976
TI  - [Obesity, an emerging problem in pediatrics. Inaugural Conference of the Eight
      National Congress of the Nutrition Spanish Society, Murcia, October 24-27, 2001].
AB  - Obesity in children and adolescents is a public health problem on the increase
      and is the most prevalent metabolic and nutritional disorder in developed
      countries. As a major non-transmissible disease, obesity has taken on epidemic
      proportions in developed countries and displaced malnutrition and infections as a
      major cause of deterioration in health and quality of life. Obesity has thus
      become one of the great health issues of the 21st century. The WHO recently
      declared obesity to be a new worldwide syndrome as it not only has a high
      prevalence in developed countries but also in the so-called emerging economies,
      the "newly westernized" or "Coca-Colanized" countries as in the case of China,
      Brazil and Eastern European states where obesity exists alongside malnutrition,
      as well as in under-developed countries where the prevalence is increasing among
      the better-off segments of the population.

PMID- 12048977
TI  - [Parenteral nutrition and identification of subpopulations with similar
      nutritional needs].
AB  - The aim of this study is to identify patients subpopulations with similar caloric
      and proteic needs (CPN) and developing and assessing the utility of standarized
      formulations of total parenteral nutrition (TPN) with equivalents supplies to the
      average patients needs of each identified subpopulation. CPN of one hundred
      metabolically stables adults patients in treatment with TPN were evaluated
      consecutively. Caloric supplies were calculated with the Harris-Benedict
      equation, with the Long corrections and proteics supplies were evaluated
      according to stress level. The identification of patients subpopulation according
      to the CPN was made through the cluster analysis with partitioning around methods
      algorithm. We considered the formulation with equivalent supplies to the average
      needs of each subpopulation was adequate to the patients caloric-proteic
      requirements when their difference was lower than 20%. The percentage of patients
      who received adequate supplies were compared between the subpopulations
      identified. In case of two subpopulations, glucose, lipids and amino acid needs
      are: 275 (CI 95%: 265-285) g, 83 (CI 95%: 78-88) g and 89 (CI 95%: 86-92) g in
      subpopulation 1 (N = 35), and 195 (CI 95%: 187-203) g, 58 (CI 95%: 56-61) g and
      74 (CI 95%: 72-77) g in subpopulation 2 (N = 65), respectively. In case of three
      subpopulations, in subpopulation 1 (N = 19), glucose, lipids and amino acid needs
      are: 295 (CI 95%: 283-306) g, 91 (CI 95%: 84-97) g and 91 (CI 95%: 86-95); 234
      (CI 95%: 227-240) g, 67 (CI 95%: 64-70) g and 84 (CI 95%: 82-86) g to the
      subpopulation 2 (N = 45) and 172 (CI 95%: 165-179) g, 55 (CI 95%: 52-57) g, and
      68 (CI 95%: 64-71) g to the subpopulation 3 (N = 36) respectively. In general,
      caloric and proteic supplies are equal to the patients needs, but there was a
      tendeny to overfeeding in patients with lower CPN. The utilization of one, two or
      three formulations with equivalent supplies to the average needs of each
      subpopulation was adequate to the patients in the 45% (CI 95%: 36%-55%), 75% (CI
      95%: 65%-83%) and 82% (CI 95%: 74%-89%), respectively. Therefore, the development
      of three normalized formulations of total parenteral nutrition allows to satisfy
      the patients nutritional needs at least the 74% of the patients.

PMID- 12048978
TI  - [Results of educational intervention in obese patients].
AB  - We have carried out an active longitudinal study to analyze the results obtained
      in the treatment of obesity by means of educational measures and a visit to a
      nurse for follow-up every 15-30 days. A total of 116 patients have been treated
      over the last two years, following referral from the medical clinic of the
      Nutrition and Dietetics Unit with a diagnosis of obesity. These patients received
      instruction in healthy eating and they were monitored in groups of 4-5
      individuals with a similar level of obesity, age and cultural level, or else
      individually in special cases. At the cut-off point, 26.7% of the patients
      continued to attend the follow-up clinic, 5.1% had completed the therapy and
      achieved the goal set (weight reduction of at least 10%), whereas 44% had
      abandoned the monitoring process, 15.5% were referred back to the medical clinic
      and 8.6% requested a voluntary discharge. The largest percentage decrease in the
      BMI (Body Mass Index) can be found among those who requested a voluntary
      discharge (ddd 12.8) over the others. By analyzing the change in the BMI between
      the start and the end of the process, we have found a non-uniform significant
      decrease (p nnn 0.001) between the different degrees. We feel that education in
      healthy eating provides patients with the necessary information for them to be
      able to achieve balanced eating habits as the basis for the treatment of obesity.
      Regular follow-up and group sessions reinforce their continuity with treatment
      and the achievement of the goals set.

PMID- 12048979
TI  - [Diet survey and evaluation of ingested nutrients in a group of HIV patients].
AB  - OBJECTIVE: To study the relationship between nutritional status, immunological
      condition, clinical progress and food consumption in a group of patients infected
      with HIV. METHOD: Longitudinal descriptive study of 30 HIV/AIDS patients.
      Anthropometric assessment (weight, height, skin folds, upper arm circumference).
      The intake of nutrients was calculated using a one-week dietary record. RESULTS:
      The mean amount of energy intake is 2,791 kcal with a 13.48% of protein, 40.12%
      of carbohydrates and 45.89% of lipids. The group of patients with weight loss
      presented a significantly greater proportion of proteins than group with normal
      weight. Patients with Kwashiorkor-like malnutrition presented an intake of
      proteins which was significantly lower than the group of well-nourished patients.
      The group of those whose nutritional status improved presented a significantly
      higher mean percentage of proteins in the diet than the other groups.
      CONCLUSIONS: The amount of the energy intake by patients is higher than that
      recommended. The diets show an excessive consumption of fats and a shortage of
      carbohydrates and proteins. Deficits are observed in vitamin B6 and vitamin E,
      magnesium and zinc. The increase in intake, by itself, does not improve the
      health status of the patients, indicating the need to provide them with the
      necessary dietary supplements from the early stages of their condition.

PMID- 12048980
TI  - Age, perfusion test results and dipyridamole reaction.
AB  - This retrospective study evaluated 933 patients referred for diagnostic nuclear
      medicine perfusion testing at 2 outpatient cardiology centers over a 7-month
      period. None of the patients were able to perform treadmill stress testing, and
      all received dipyridamole as a pharmacological stress. The authors found that 44%
      of the patients had an adverse reaction to dipyridamole. A correlational analysis
      of patients who did and did not have adverse reactions indicated that patients
      who exhibited some form of adverse reaction to dipyridamole were 10% more likely
      to have an abnormal perfusion test. In addition, age-group comparisons between
      patients 70 years or older and those younger than 70 years demonstrated that the
      younger group had a statistically greater probability of having an adverse
      reaction to dipyridamole.

PMID- 12048981
TI  - Student self-evaluation in clinical education.
AB  - Student self-evaluation can be an important component of clinical education.
      Through self-evaluation, students may experience increased satisfaction with the
      educational process and decreased anxiety during evaluation. They also learn the
      process and importance of goal setting. This article reports on the development
      and use of a student self-evaluation instrument in a baccalaureate-level
      radiologic technology program. The instrument's reliability and validity were
      examined, and information was collected regarding students' satisfaction with the
      self-assessment process. The authors found that student self-evaluation improved
      the evaluation process for both students and instructors.

PMID- 12048982
TI  - CT assessment of CNS complications of AIDS.
AB  - Although acquired immunodeficiency syndrome (AIDS) is not directly fatal,
      individuals with the disease are susceptible to a host of life-threatening
      opportunistic infections and complications. This article focuses on the central
      nervous system (CNS) complications of HIV/AIDS and computed tomography's role in
      diagnosing these conditions. After completing the article, readers will know the
      signs and symptoms, causes or proposed causes and computed tomographic (CT)
      appearance of 4 important CNS complications of HIV/AIDS: Progressive multifocal
      leukoencephalopathy (PML). Toxoplasmosis. CNS lymphoma. AIDS dementia complex
      (ADC).

PMID- 12048983
TI  - Digital mammography: state of the art.
AB  - After completing this update on digital mammography, readers will: Understand
      some limitations of film-screen mammography. Know the potential advantages and
      disadvantages of digital mammography. Compare and contrast some different digital
      mammography systems. Describe how digital images are captured, processed,
      displayed and stored. Know how digital mammography affects radiation dose,
      exposure time and contrast resolution. Understand how digital images are
      transmitted. Be familiar with new techniques that build on digital mammography,
      such as 3-D mammography, digital subtraction mammography and computer-aided
      detection.

PMID- 12048984
TI  - MR's role in assessing multiple sclerosis.

PMID- 12048985
TI  - Surveys track rising wages, other trends.

PMID- 12048986
TI  - Strategies for effective confrontation.
AB  - Radiology managers who confront staff members in an appropriate manner leave no
      doubt about their expectations. They demand excellent and consistent performance
      and do not settle for less. A radiology manager who uses confrontation shows that
      he or she cares enough about the staff to challenge poor performance. When the
      manager confronts an employee about performance, he or she sends a message to all
      employees that mediocre work is not acceptable. The techniques used in
      confrontation ultimately determine how the confrontation is received and how
      effective it is. The manager's attitude toward the staff member and ability to
      verbalize expected outcomes significantly influence how effective confrontation
      is in motivating staff to improve. Radiology managers who show respect, empathy
      and support for staff and establish firm expectations find confrontation to be a
      useful tool.

PMID- 12048987
TI  - CT screening business fueled by fear.

PMID- 12048988
TI  - Nuclear medicine education in Kuwait.

PMID- 12048989
TI  - Misconceptions about protective aprons.

PMID- 12048991
TI  - Ultrasound during pregnancy.

PMID- 12048992
TI  - The people who make organizations go--or stop.
AB  - Managers invariably use their personal contacts when they need to, say, meet an
      impossible deadline or learn the truth about a new boss. Increasingly, it's
      through these informal networks--not just through traditional organizational
      hierarchies--that information is found and work gets done. But to many senior
      executives, informal networks are unobservable and ungovernable--and, therefore,
      not amenable to the tools of management. As a result, executives tend to work
      around informal networks or, worse, try to ignore them. When they do acknowledge
      the networks' existence, executives fall back on intuition--scarcely a dependable
      tool--to guide them in nurturing this social capital. It doesn't have to be that
      way. It is entirely possible to develop and manage informal networks
      systematically, say management experts Cross and Prusak. Specifically, senior
      executives need to focus their attention on four key role-players in informal
      networks: Central connectors link most employees in an informal network with one
      another; they provide the critical information or expertise that the entire
      network draws on to get work done. Boundary spanners connect an informal network
      with other parts of the company or with similar networks in other organizations.
      Information brokers link different subgroups in an informal network; if they
      didn't, the network would splinter into smaller, less effective segments. And
      finally, there are peripheral specialists, who anyone in an informal network can
      turn to for specialized expertise but who work apart from most people in the
      network. The authors describe the four roles in detail, discuss the use of a well
      established tool called social network analysis for determining who these role
      players are in the network, and suggest ways that executives can transform
      ineffective informal networks into productive ones.

PMID- 12048990
TI  - Positioning is key to cancer detection.

PMID- 12048993
TI  - Spinning out a star.
AB  - Spinouts rarely take off; most, in fact, fall into one or more of four traps that
      doom them from the start. Some companies spin out ventures that are too close to
      the core of their businesses, in effect selling off their crown jewels.
      Sometimes, a parent company uses the spinout primarily to pawn off debt or
      expenses or to quickly raise external capital for itself. Other times, a company
      may try to spin out an area of its business that lacks one or more of the
      critical legs of a successful company--a coherent business model, say, or a solid
      financial base. And in many cases, parent companies can't bring themselves to
      sever their ownership ties and give up control of their spinouts. R.J. Reynolds,
      the tobacco giant, managed to avoid these traps when it successfully spun out a
      most unlikely venture, the pharmaceutical company Targacept. As the story
      illustrates, the problem with spinouts is similar to the problem of rich
      children. Their parents have the wherewithal to spoil them or shelter them or
      cling to them, but what they need is tough love and discipline--much the same
      discipline that characterizes successful start-ups. R.J. Reynolds recognized that
      it didn't know that much about the pharmaceutical business and couldn't merely
      try to spin out a small clone of itself. It had to treat the venture as if it
      were essentially starting from scratch, with a passionate entrepreneurial leader,
      a solid business plan, help from outside partners in the industry, and ultimately
      substantial venture backing. That these lessons are less obvious to executives
      contemplating spinning out ventures closer to their core businesses may be why so
      many spinouts fail.

PMID- 12048994
TI  - Hidden minds. When it comes to mining consumers' views, we've only scratched the
      surface.

PMID- 12048995
TI  - A survival guide for leaders.
AB  - Let's face it, to lead is to live dangerously. While leadership is often viewed
      as an exciting and glamorous endeavor, one in which you inspire others to follow
      you through good times and bad, such a portrayal ignores leadership's dark side:
      the inevitable attempts to take you out of the game. This is particularly true
      when a leader must steer an organization through difficult change. When the
      status quo is upset, people feel a sense of profound loss and dashed
      expectations. They may need to undergo a period of feeling incompetent or
      disloyal. It's no wonder they resist the change and often try to eliminate its
      visible agent. This "survival guide" offers a number of techniques--relatively
      straightforward in concept but difficult to execute--for protecting yourself as
      you lead such a change initiative. Adapted from the book Leadership on the Line:
      Staying Alive Through the Dangers of Leading (Harvard Business School Press,
      2002), the article has two main parts. The first looks outward, offering tactical
      advice about relating to your organization and the people in it. It is designed
      to protect you from those who would push you aside before you complete your
      initiatives. The second looks inward, focusing on your own needs and
      vulnerabilities. It is designed to keep you from bringing yourself down. The hard
      truth is that it is not possible to experience the rewards and joys of leadership
      without experiencing the pain as well. But staying in the game and bearing that
      pain is worth it, not only for the positive changes you can make in the lives of
      others but also for the meaning it gives your own.

PMID- 12048996
TI  - Charting your company's future.
AB  - Few companies have a clear strategic vision. The problem, say the authors, stems
      from the strategic-planning process itself, which usually involves preparing a
      large document, culled from a mishmash of data provided by people with
      conflicting agendas. That kind of process almost guarantees an unfocused
      strategy. Instead, companies should design the strategic-planning process by
      drawing a picture: a strategy canvas. A strategy canvas shows the strategic
      profile of your industry by depicting the various factors that affect
      competition. And it shows the strategic profiles of your current and potential
      competitors as well as your own company's strategic profile--how it invests in
      the factors of competition and how it might in the future. The basic component of
      a strategy canvas--the value curve--is a tool the authors created in their
      consulting work and have written about in previous HBR articles. This article
      introduces a four-step process for actually drawing and discussing a strategy
      canvas. Readers will learn how one European financial services company used this
      process to create a distinct and easily communicable strategy. The process begins
      with a visual awakening. Managers compare their business's value curve with
      competitors' to discover where their strategy needs to change. In the next step-
      visual exploration--managers do field research on customers and alternative
      products. At the visual strategy fair, the third step, managers draw new
      strategic profiles based on field observations and get feedback from customers
      and peers about these new proposals. Once the best strategy is created from that
      feedback, it's time for the last step--visual communication. Executives
      distribute "before" and "after" strategic profiles to the whole company, and only
      projects that will help move the company closer to the "after" profile are
      supported.

PMID- 12048997
TI  - The very real dangers of executive coaching.
AB  - A personal coach to help your most promising executives reach their potential-
      sounds good, doesn't it? But, according to Steven Berglas, executive coaches can
      make a bad situation worse. Because of their backgrounds and biases, they ignore
      psychological problems they don't understand. Companies need to consider
      psychotherapeutic intervention when the symptoms plaguing an executive are
      stubborn or severe. Executives with issues that require more than coaching come
      in many shapes and sizes. Consider Rob Bernstein, an executive vice president of
      sales at an automotive parts distributor. According to the CEO, Bernstein had
      just the right touch with clients but caused personnel problems inside the
      company. The last straw came when Bernstein publicly humiliated a mail clerk who
      had interrupted a meeting to ask someone to sign for a package. At that point,
      the CEO assigned Tom Davis to coach Bernstein. Davis, a former corporate lawyer,
      worked with Bernstein for four years. But Davis only exacerbated the problem by
      teaching Bernstein techniques for "handling" employees--methods that were
      condescending at best. While Bernstein appeared to be improving, he was in fact
      getting worse. Bernstein's real problems went undetected, and when his boss left
      the company, he was picked as the successor. Soon enough, Bernstein was again in
      trouble, suspected of embezzlement. This time, the CEO didn't call Davis;
      instead, he turned to the author, a trained psychotherapist, for help. Berglas
      soon realized that Bernstein had a serious narcissistic personality disorder and
      executive coaching could not help him. As that tale and others in the article
      teach us, executives to be coached should at the very least first receive a
      psychological evaluation. And company leaders should beware that executive
      coaches given free rein can end up wreaking personnel havoc.

PMID- 12048998
TI  - Value acceleration: lessons from private-equity masters.
AB  - The most successful private-equity firms regularly spearhead dramatic business
      transformations, creating exceptional returns for their investors. To understand
      how those firms do it, the authors studied more than 2,000 PE transactions over
      the past ten years and discovered that the top performers' success stems from the
      rigor with which they manage their businesses. This article describes the four
      management disciplines vital to the success of the best PE firms. First, for each
      business, they define an investment thesis: a brief, clear statement of how to
      make the business more valuable within three to five years. The thesis, which
      guides all actions by the company, usually focuses on growth. PE firms know that
      the demonstration of a path to strong growth produces the big returns on
      investment. Second, they don't measure too much. They zero in on a few financial
      indicators that most clearly reveal the business's progress in increasing its
      value. They watch cash more closely than earnings and tailor performance measures
      to each business, rather than imposing one set of measures across their entire
      portfolio. Third, they work their balance sheets, mining undervalued assets,
      turning fixed assets into sources of financing, and aggressively managing their
      physical capital. Last, they make the center the shareholder. Corporate staffs in
      PE firms make unsentimental investment decisions, buying and selling businesses
      when the price is right and bringing in new management when performance falters.
      These firms also keep their corporate centers extremely lean. By adopting these
      four disciplines, executives at public companies should be able to reap
      significantly greater returns from their own business units.

PMID- 12048999
TI  - Outpatient civil commitment laws: an overview.

PMID- 12049000
TI  - Laboratory investigation of an E. coli O157:H7 outbreak associated with swimming
      in Battle Ground Lake, Vancouver, Washington.
AB  - Escherichia coli O157:H7 has been associated with a number of waterborne
      outbreaks, but it has never been recovered from an implicated environment. This
      paper reports on an August 1999 outbreak of E. coli O157:H7 associated with
      swimming in Battle Ground Lake in Clark Country, Washington. E. coli O157:H7 was
      isolated from duck feces, as well as from two water samples. The authors used
      pulsed-field gel electrophoresis to compare these isolates with patient isolates
      for genetic homology. All the isolates yielded the same restriction fragment
      patterns. In addition, using polymerase chain reaction, the authors found patient
      isolates and environmental isolates to have the same virulence factors (Stx,
      eaeA, and hly).

PMID- 12049001
TI  - Graywater use still a gray area.

PMID- 12049002
TI  - Laws on defamation: could they affect environmental health professionals?

PMID- 12049003
TI  - PCBs: measuring the danger.

PMID- 12049005
TI  - More on CDC's promising initiative to strengthen environmental health.

PMID- 12049004
TI  - A primer on sampling for biological contaminants, Part Two: Air sampling
      instrumentation.

PMID- 12049006
TI  - Grading systems for retail food facilities: preference reversals of environmental
      health professionals.
AB  - The authors asked a random sample of 89 environmental health professionals in
      California about their willingness to dine in restaurants under three different
      scenarios: 1) The restaurant has received an inspection grade of A, B, or C and
      is one they normally dine in; 2) the restaurant was closed for health violations
      but recently has reopened with a grade of A, B, or C, and 3) the restaurant has
      been given a numerical score only (88, 78, 68, or 58). A paired-samples sign test
      showed differences among the scenarios with statistical significance above 99.9
      percent. Professionals were less willing to dine in a restaurant if it recently
      had been closed and more willing to dine in it if only the numerical scores were
      given. The results indicate various cases in which there is a preference reversal
      from the expected order of A, B, and C; these results are largely consistent with
      those of an earlier study of university students. The study reported here
      suggests that the attitudes of environmental health professionals are consistent
      with those of the public they represent, and that most professionals are quite
      willing to distinguish grades depending on the underlying conditions provided.
      Significant differences were found among environmental health professionals
      depending on whether they had experience with grading systems. In the interests
      of encouraging thought and dialogue on the subject, this paper closes with a
      courtroom scenario that examines some repercussions of grading systems.

PMID- 12049007
TI  - [Successful management of early aortic root abscess with aortic homograft
      implantation in children after Ross operation].
AB  - The Ross operation is the best surgical procedure for aortic valve replacement in
      children of all age groups. A 3.5 years old boy developed early autograft
      endocarditis (9 days) following a straightforward Ross operation. Due to
      progressive neo-aortic valve destruction and aortic root abscess extending to the
      mitral annulus and valve, the pulmonary autograft had to be removed. A
      cryopreserved aortic homograft with its attached mitral valve leaflet was used to
      reconstruct the left ventricular outflow tract and repair the native mitral valve
      defect.

PMID- 12049008
TI  - [Surgical treatment of giant hemangiomas of the liver].
AB  - Spontaneous rupture of liver hemangiomas is exceptional, they rarely increase in
      size. Elective surgery of liver hemangiomas is safe and effective. In our
      teaching hospital during a 5-year period 9 patients underwent elective surgery
      for giant liver hemangiomas, one more patient required urgent operation for
      spontaneous rupture. Indications for elective surgery were: abdominal pain in 5
      patients, enlargement in 1 patient, and 3 patients were worried about the risk of
      rupture or having a tumor left in situ. The average age of our four male and six
      female patients was 44.5 years (30-58). The median largest dimension of the
      lesions was 8.5 cm (5.5-14); six of them located in the right, four in the left
      lobe. Enucleation was performed in most patients (8, mostly of them in the right
      lobe); anatomical resections were performed only in two cases (left lobectomy).
      There was no postoperative mortality, the only complication was mild pneumonia in
      one patient. Elective surgery is indicated only in a small number of patients
      with hemangiomas, it should be limited to giant, symptomatic tumors or those with
      a documented tendency to increase in size. The type of resection depends on the
      site and the size of the lesion. Enucleation can be performed rapidly and safely
      in most patients and as such it is preferable to anatomical resection.

PMID- 12049009
TI  - [Reoperations for early recurrent occlusions following femoropopliteal and
      femorocrural bypasses].
AB  - We analyse the early results of 333 patients who had been operated on because of
      femoropopliteal occlusions between 1996 and 2000. Most interventions (90.4%) were
      below knee reconstructions. The rate of crural bypasses was high (40.5%). We
      examined whether the length and type of the graft influenced the outcome of the
      primary operation. If below knee bypass was necessary in every operation
      autologous grafts were preferred either partially or entirely (saphenous vein or
      arm vein). The number of reocclusions and amputations was significantly higher if
      the distal anastomosis involved the crural arteries (p < 0.02), or the graft was
      not autologous (p < 0.01). There was no statistical difference between early
      results of saphena and arm vein bypasses (p = 0.2). Thirty-six reoperations were
      performed for early graft failures. Either the patient's general condition or
      local findings did not allow reoperations in 17 patients with occluded graft,
      they were treated conservatively. Nine patients died after surgery (2.7%). In the
      postoperative period 21 major amputations were necessary (6.3%), in six cases the
      graft was patient. After reoperations 7 patients needed amputations (19.4%), in
      the 17 patients not reoperated on the second time, 8 amputations were necessary
      (47%), the difference is significant (p < 0.05). We are convinced about the
      importance of urgent reoperation in case of early graft occlusion. If the run-off
      to the distal arteries was doubtful intraoperative angiography was performed.
      When distal extension of the operation was necessary we tried to use autologous
      grafts. The amputation rate was significantly lower after reoperations if the
      cause of graft occlusion was found and corrected compared to simple
      thrombectomies (p < 0.05).

PMID- 12049010
TI  - [Cryosurgery and endoscopy in the treatment of varicose veins].
AB  - Multiplex wide incisions and often deforming scars following varicose surgery are
      out of date. Nowadays cryoprobes are used to remove epifascial varicose veins,
      while endoscopy is used to treat transfascial (perforating) venous insufficiency.
      We analyse the results of 1000 cryovaricectomies performed in the last 8 years.
      Complications developed in 5.8%, mostly were self-limiting. It is a fast
      operation, offering good aesthetic result, and hospital stay is short. Subfascial
      endoscopic perforating veins surgery (SEPS) have been carried out in 2 years in
      28 patients, 8 had active ulcers, combined operation have been performed in 20
      patients. There were 3 wound complications, which was a very good result compared
      with high complication rate of earlier used open divisions. The biggest advantage
      of the procedure is, that it can be performed even if the ulcer is active, since
      the operation is performed on intact area. Both methods meet the requirements of
      minimal invasive surgery, with excellent cosmetic and functional results.

PMID- 12049011
TI  - [Surgical treatment for metastatic renal cell tumors of the lung].
AB  - Number of resection for lung metastasis in Hungary is low, however surgery
      provides benefit for patients using an integrated oncological therapeutical
      protocol. The authors give a retrospective analysis of 57 patients operated on
      for metastatic renal cell tumor to the lung. Metastases were discovered most
      frequently by x-ray picture of an accidental investigation or screening at
      symptom-free patients and in 32 cases solitary and in 25 cases multiple deposits
      were proved. After selection's protocol 20 patients underwent lobectomy and 32
      ones wedge resection while in 5 cases only biopsy was done. Out of 52 cases 33
      complete resections were performed and in 9 cases incomplete resection was
      carried out. The cumulative five-year survival time was 35%, following complete
      resection 45%. If DFI was longer than 12 months, survival was observed 38% at
      five year. SUMMARY: On basis of our experience after surgery of metastatic renal
      cell tumors to the lung might expect favourable survival which is significantly
      better after complete resection of lung metastasis and after longer than 12
      months DFI.

PMID- 12049012
TI  - [Skin closure in inguinal hernia repair with rapidly absorbing Polyglactin
      910/370 (Vicryl-Rapide) suture material].
AB  - OBJECTIVE: Results of fast absorbing Poliglactin 910/370 suture material were
      assessed in skin closure following invaginal hernia repairs. METHODS: Fifty
      consecutive patients undergoing invaginal hernia repair were prospectively and
      randomly assigned in two groups. In Group I, wounds were closed with conventional
      absorbable subcutaneous Polyglactin 910 (VICRYL, ETHICON) and non absorbable
      cutaneous Monofilament Nylon (ETHILON, ETHICON) stitches. In Group II, running
      subcutaneous and intradermic irradiated Polyglactin 910/370 (VICRYL-Rapide,
      ETHICON) sutures were used. The time of skin closure, the price of the suture
      material, short and middle term cosmetic results, complications in wound healing
      and the subjective comfort of patients were noted. RESULTS: The cost of skin
      closing was similar, while the need for further medical wistis was lower in the
      VICRYL-Rapide group. The wound healing process and it's cosmetic results were
      similar. Patients in Group II experienced less discomfort, due to the avoidance
      of suture removal. CONCLUSION: The rapidly resorbing suture material (VICRYL
      Rapide) is a cost effective choice for closing the skin of invaginal hernia
      repairs and probably of other clean operations.

PMID- 12049013
TI  - [Hormonal and hyperglycemic response in laparoscopic and open cholecystectomy].
AB  - The aim of the study is to evaluate the intensity of the operative trauma during
      laparoscopic and open cholecystectomy measured by hormonal (cortisol level) and
      metabolic (blood sugar level) response. Prospective randomized study was
      conducted in seventy patients with cholelithiasis. They were divided in two
      groups: thirty five underwent laparoscopic cholecystectomy and thirty five
      underwent open cholecystectomy (control group). Mean cortisol concentration and
      glucose concentration were measured preoperatively and postoperatively after 2,
      4, 8, 12, 24 and 48 hours. The examined groups were comparable in age and sex.
      Preoperative plasma cortisol concentration was within normal range in both
      groups. Postoperatively plasma cortisol level increased in the laparoscopically
      operated group, and peak level occurred eight hours after surgery (692.6 +/- 27.2
      nmol/L). Peak plasma cortisol level in control group developed 8 hours
      postoperatively (841.1 +/- 33.2 nmol/L). The mean cortisol concentration was
      significantly higher (p < 0.05) following open procedure between fourth and 48th
      postoperative hour. Mean plasma glucose concentrations after laparoscopic and
      open cholecystectomy were significantly higher (p < 0.05) than preoperative
      values. The mean glucose concentration during the initial 24 hours was
      significantly higher (p < 0.05) following open cholecystectomy.

PMID- 12049014
TI  - [To the Editor in Chief: Procalcitonin rapid test in intensive care].

PMID- 12049015
TI  - [Continuous postoperative epidural analgesia in abdominal surgery using
      ropivacain].
AB  - We studied the selective block on patients receiving epidural Ropivacain (R)
      infusion for postoperative analgesia after major abdominal surgery. Twenty
      patients received R and twenty patients received Bupivacain (B) via peridural
      catheter during and after surgery. The patients' age ranged between 40 and 80 and
      they belonged to ASA I, II and III risk group. The epidural catheter was inserted
      one day before surgery and the proper position was tested by 80 mg Lidocaine. The
      epidural needle was inserted via T10-L1 interspaces in upper abdominal surgery
      and through L1-L3 interspaces in lower abdominal surgery. After the operation
      continuous epidural infusion of 2 mg/ml solution of R or 2.5 mg/ml solution of B
      was started. The infusion rate was changed according to the grade of sensory and
      motor block. The following parameters were observed during the postoperative 72
      hours: blood pressure, heart rate, arterial blood O2 saturation, modified Bromage
      (BMG) score, verbal analogue scale (VAS), the spread of sensory block.
      Satisfactory sensory blockade was achieved with both local anaesthetics. The
      required daily dose of R and B increased during 72 hours. VAS scores reached
      their maximum level within 24 hours and were lower in the R group than in the B
      group but the difference was not significant. We experienced that 0.25% B causes
      more intense motor block than 0.2% R in equianalgetic dose but the difference did
      not reach a significant level. The infusion rate was often decreased because of
      the unwanted motor block caused by 0.25% B leading to insufficient postoperative
      analgesia. Because of this fact patients receiving B required opioid addition
      more often. Our conclusion is that R/B relative dose ratio is 1.2 suggesting that
      these local anaesthetics have different analgesic potency.

PMID- 12049016
TI  - [Massive gastrointestinal bleeding in Henoch-Schoenlein purpura in an adult].
AB  - Henoch-Schoenlein syndrome in an adult patient, localised only to the
      gastrointestinal system is very rare. A 50 year old male was treated in our
      Intensive Department because of acute respiratory distress syndrome (ARDS) and
      renal failure. After temporary improvement massive gastrointestinal bleeding
      developed with shock. Blood was found in the descending duodenum without evident
      pathology at endoscopy. Angiogram showed bleeding at the hepatic flexure of the
      colon, which was successfully treated by a coil and bleeding was also present in
      the terminal part of the small intestine. The catheter was left in situ and the
      bleeding part of the bowel was painted intraoperatively, so we could resect the
      stained part of the intestine. Because of rebleeding, bowel resection was
      performed an other two occasions in the same way. The histology of the bowel
      showed Henoch-Schoenlein syndrome in each specimen. Our patient was totally non
      responsive to treatment, which is usually successful in this disease. After the
      resections the bleeding stopped temporarily, but as the underlying disease was
      unmanageable the patient died but we have not found any surgical complication at
      autopsy. We think that this method in the surgical treatment of massive
      intestinal bleeding is very useful and effective.

PMID- 12049017
TI  - [High-pressure air-blast injury of the esophagus].
AB  - Blast injuries causing pneumatic damage to the oesophagus are very rare. Patients
      usually present with respiratory distress, subcutaneous and mediastinal
      emphysema, and may also have pneumothorax. Ruptures need early repair to avoid
      serious morbidity and potential lethal complications. We report about a
      successfully treated 47-year-old patient, who has been admitted to our department
      with compressed air injury of the oesophagus.

PMID- 12049018
TI  - In memoriam: Richard E. Whalen.

PMID- 12049019
TI  - Sex in long-term relationships: a systemic approach to sexual desire problems.
AB  - Most concepts of sexual desire implicitly refer to early phases of attraction and
      youthful living systems. For an alternative conceptual approach of decreasing
      sexual desire in long-term relationships, three points are addressed which
      influence the definition and theorizing on decreasing sexual interest: (1)
      passive vs. active negation of desire; (2) desire as part of sexual function vs.
      desire as passion in its own right; and (3) desire as individual trait vs.
      emergent function of structural coupling of the partners.

PMID- 12049020
TI  - Preference for aggressive and sexual stimuli in children with disruptive behavior
      disorder and normal controls.
AB  - Children with disruptive behavior disorders (DBD) have poor social skills and
      show aggressive interaction patterns. There is evidence from prospective studies
      of an association between early physical abuse, later social information
      processing patterns, and aggressive behavior. A pattern of hypervigilance to
      hostile cues has been found in DBD children, but very few studies have
      investigated encoding or perceptual preference for specific classes of stimuli.
      Some DBD children have a suspected history of sexual abuse and a few have
      themselves been sexually offensive. Our belief that the sexuality of DBD children
      should be investigated raised the issue of how to go about doing this. A
      procedure was developed in which we measured the relative preference for sexual
      and aggressive stimuli in comparison to other stimulus categories, and the data
      of DBD children were compared with those of normal controls. It was found that
      DBD children preferred viewing sexual slides and had a lower preference for
      nonaggressive slides. Furthermore, boys in general preferred viewing aggressive
      slides, did so for longer, and chose them earlier, whereas the more aggressive
      DBD children distinguished themselves in selecting aggressive stimuli earlier.
      The implications of these findings were discussed and it was concluded that
      sexuality is clearly an important topic to address in aggressive children in
      general and not only in the abused ones.

PMID- 12049021
TI  - Postoperative psychological functioning of adolescent transsexuals: a Rorschach
      study.
AB  - The Rorschach Comprehensive System was used to assess postoperative psychological
      functioning in transsexuals who applied for sex reassignment in adolescence. We
      investigated a group of 22 consecutive adolescent transsexuals, who were
      otherwise psychologically well adapted. Nineteen subjects provided valid
      Rorschach protocols before and after sex reassignment. The most notable change
      found was an increase in X + %, reflecting a decrease in both distorted
      perception and idiosyncratic perception. Little support was found for the idea of
      major psychological deterioration for the patients as a group. Rather, the
      results suggest stability in psychological functioning over time. The Rorschach
      findings are consistent with questionnaire data from earlier studies, with the
      exception that the Rorschach data may point to some improvement in reality
      testing.

PMID- 12049022
TI  - Sexual experiences in childhood: young adults' recollections.
AB  - Childhood sexuality and children's sexual experiences have become increasingly
      important to study because our knowledge on the impact of sexually abusive
      experiences on children's developing sexuality has increased. The main aim of
      this paper was to study aspects of young adults' recollections of their sexual
      experiences before the age of 13, solitary and shared, mutual as well as
      coercive. Anonymous questionnaires were answered by 269 final year, senior high
      school students, mean age 18.6 years; 82.9% of the students reported solitary
      sexual experiences and 82.5% had mutual experiences together with another child.
      Most of the children had their experiences together with a same-age friend. Girls
      had more same-sex experiences than boys did. Thirteen percent reported coercive
      experiences where they had been tricked, bribed, threatened, or physically forced
      into participation. Some children, 8.2%, had coerced another child into
      participation in sexual activities. The majority thought of their childhood
      experiences as normal. There were also 6.3% of the respondents who had had
      inappropriate sexual experiences with someone at least 5 years older, the
      majority being girls. Gender differences were evident in several respects: girls
      were more often coerced, they felt more guilt, and they had far less experience
      of masturbation, whereas boys were somewhat more active in explorative activities
      on their own as well as with peers. Some kind of coercive sexual experiences
      appears to be part of growing up for quite a few children, although in general
      the years before puberty seem to be years of frequent mutual sexual exploration
      and experimentation.

PMID- 12049023
TI  - Sexual motivation and the duration of partnership.
AB  - The variation of sexual motivation with duration of partnership is analyzed in
      data from a survey of German students. The sample of 1865 includes only students
      aged 19-32 who reported to be heterosexual and to live in a steady partnership.
      Main results are (1) sexual activity and sexual satisfaction decline in women and
      men as the duration of partnership increases; (2) sexual desire only declines in
      women; and (3) desire for tenderness declines in men and rises in women. Because
      these results are based on cross-sectional data, a longitudinal explanation is
      precarious. Individual differences in mating strategy associated with the
      probability of having a partnership of shorter or longer duration at the time of
      the survey may account for some part of the findings. This possibility set aside,
      post hoc explanations for the results as reflecting a modal time course of
      partnership are evaluated with regard to habituation, routine, gender role
      prescriptions, and polarization of roles. In addition, an explanation from
      evolutionary psychology is offered, entailing the following ideas: the
      psychological mechanisms of attachment in an adult pair bond have evolved from
      the parent-child bond. Due to this nonsexual origin, a stable pair-bond does not
      require high levels of sexual desire, after an initial phase of infatuation has
      passed. Nevertheless, male sexual desire should stay at a high level because it
      was selected for in evolutionary history as a precaution against the risk of
      sperm competition. The course of female sexual desire is assumed to reflect an
      adaptive function: to boost attachment in order to establish the bond.

PMID- 12049024
TI  - Does semen have antidepressant properties?
AB  - In a sample of sexually active college females, condom use, as an indirect
      measure of the presence of semen in the reproductive tract, was related to scores
      on the Beck Depression Inventory. Not only were females who were having sex
      without condoms less depressed, but depressive symptoms and suicide attempts
      among females who used condoms were proportional to the consistency of condom
      use. For females who did not use condoms, depression scores went up as the amount
      of time since their last sexual encounter increased. These data are consistent
      with the possibility that semen may antagonize depressive symptoms and evidence
      which shows that the vagina absorbs a number of components of semen that can be
      detected in the bloodstream within a few hours of administration.

PMID- 12049025
TI  - Sexual activity as a trigger for ventricular tachycardia in a patient with
      implantable cardioverter defibrillator.
AB  - Occurrence of life threatening arrhythmias and sudden death during or following
      sexual activity is infrequent. We describe a patient with an implantable
      cardioverter defibrillator who developed increased ventricular ectopic activity
      followed by sustained ventricular tachycardia during extramarital coitus. A
      review of literature and management is discussed.

PMID- 12049026
TI  - GP recruitment and retention: a qualitative analysis of doctors' comments about
      training for and working in general practice.
AB  - BACKGROUND AND AIMS: General practice in the UK is experiencing difficulty with
      medical staff recruitment and retention, with reduced numbers choosing careers in
      general practice or entering principalships, and increases in less-than-full-time
      working, career breaks, early retirement and locum employment. Information is
      scarce about the reasons for these changes and factors that could increase
      recruitment and retention. The UK Medical Careers Research Group (UKMCRG)
      regularly surveys cohorts of UK medical graduates to determine their career
      choices and progression. We also invite written comments from respondents about
      their careers and the factors that influence them. Most respondents report high
      levels of job satisfaction. A noteworthy minority, however, make critical
      comments about general practice. Although their views may not represent those of
      all general practitioners (GPs), they nonetheless indicate a range of concerns
      that deserve to be understood. This paper reports on respondents' comments about
      general practice. ANALYSIS OF DOCTORS' COMMENTS: Training Greater exposure to
      general practice at undergraduate level could help to promote general practice
      careers and better inform career decisions. Postgraduate general practice
      training in hospital-based posts was seen as poor quality, irrelevant and run as
      if it were of secondary importance to service commitments. In contrast, general
      practice-based postgraduate training was widely praised for good formal teaching
      that met educational needs. The quality of vocational training was dependent upon
      the skills and enthusiasm of individual trainers. Recruitment problems Perceived
      deterrents to choosing general practice were its portrayal, by some hospital
      based teachers, as a second class career compared to hospital medicine, and a
      perception of low morale amongst current GPs. The choice of a career in general
      practice was commonly made for lifestyle reasons rather than professional
      aspirations. Some GPs had encountered difficulties in obtaining posts in general
      practice suited to their needs, while others perceived discrimination. Newly
      qualified GPs often sought work as non-principals because they felt too
      inexperienced for partnership or because their domestic situation prevented them
      from settling in a particular area. Changes to general practice The 1990 National
      Health Service (NHS) reforms were largely viewed unfavourably, partly because
      they had led to a substantial increase in GPs' workloads that was compounded by
      growing public expectations, and partly because the two-tier system of fund
      holding was considered unfair. Fund-holding and, more recently, GP commissioning
      threatened the GP's role as patient advocate by shifting the responsibility for
      rationing of health care from government to GPs. Some concerns were also
      expressed about the introduction of primary care groups (PCGs) and trusts (PCTs).
      Together, increased workload and the continual process of change had, for some,
      resulted in work-related stress, low morale, reduced job satisfaction and quality
      of life. These problems had been partially alleviated by the formation of GP co
      operatives. Retention difficulties Loss of GPs' time from the NHS workforce
      occurs in four ways: reduced working hours, temporary career breaks, leaving the
      NHS to work elsewhere and early retirement. Child rearing and a desire to pursue
      interests outside medicine were cited as reasons for seeking shorter working
      hours or career breaks. A desire to reduce pressure of work was a common reason
      for seeking shorter working hours, taking career breaks, early retirement or
      leaving NHS general practice. Other reasons for leaving NHS general practice,
      temporarily or permanently, were difficulty in finding a GP post suited to
      individual needs and a desire to work abroad. CONCLUSIONS: A cultural change
      amongst medical educationalists is needed to promote general practice as a career
      choice that is equally attractive as hospital practice. The introduction of Pre
      Registration House Officer (PRHO) placements in general practice and improved
      flexibility of GP vocational training schemes, together with plans to improve the
      quality of Senior House Officer (SHO) training in the future, are welcome
      developments and should address some of the concerns about poor quality GP
      training raised by our respondents. The reluctance of newly qualified GPs to
      enter principalships, and the increasing demand from experienced GPs for less
      than-full-time work, indicates a need for a greater variety of contractual
      arrangements to reflect doctors' desires for more flexible patterns of working in
      general practice.

PMID- 12049027
TI  - An evidence-based approach to assessing older people in primary care.

PMID- 12049028
TI  - Primary Care Research Team Assessment (PCRTA): development and evaluation.
AB  - BACKGROUND: Since the early 1990s the United Kingdom (UK) Department of Health
      has explicitly promoted a research and development (R&D) strategy for the
      National Health Service (NHS). General practitioners (GPs) and other members of
      the primary care team are in a unique position to undertake research activity
      that will complement and inform the research undertaken by basic scientists and
      hospital-based colleagues and lead directly to a better evidence base for
      decision making by primary care professionals. Opportunities to engage in R&D in
      primary care are growing and the scope for those wishing to become involved is
      finally widening. Infrastructure funding for research-active practices and the
      establishment of a range of support networks have helped to improve the research
      capacity and blur some of the boundaries between academic departments and
      clinical practice. This is leading to a supportive environment for primary care
      research. There is thus a need to develop and validate nationally accepted
      quality standards and accreditation of performance to ensure that funders,
      collaborators and primary care professionals can deliver high quality primary
      care research. Several strategies have been described in national policy
      documents in order to achieve an improvement in teaching and clinical care, as
      well as enhancing research capacity in primary care. The development of both
      research practices and primary care research networks has been recognised as
      having an important contribution to make in enabling health professionals to
      devote more protected time to undertake research methods training and to
      undertake research in a service setting. The recognition and development of
      primary care research has also brought with it an emphasis on quality and
      standards, including an approach to the new research governance framework.
      PRIMARY CARE RESEARCH TEAM ASSESSMENT: In 1998, the NHS Executive South and West,
      and later the London Research and Development Directorate, provided funding for a
      pilot project based at the Royal College of General Practitioners (RCGP) to
      develop a scheme to accredit UK general practices undertaking primary care R&D.
      The pilot began with initial consultation on the development of the process, as
      well as the standards and criteria for assessment. The resulting assessment
      schedule allowed for assessment at one of two levels: Collaborative Research
      Practice (Level I), with little direct experience of gaining project or
      infrastructure funding Established Research Practice (Level II), with more
      experience of research funding and activity and a sound infrastructure to allow
      for growth in capacity. The process for assessment of practices involved the
      assessment of written documentation, followed by a half-day assessment visit by a
      multidisciplinary team of three assessors. IMPLEMENTATION--THE PILOT PROJECT:
      Pilot practices were sampled in two regions. Firstly, in the NHS Executive South
      West Region, where over 150 practices expressed an interest in participating.
      From these a purposive sample of 21 practices was selected, providing a range of
      research and service activity. A further seven practices were identified and
      included within the project through the East London and Essex Network of
      Researchers (ELENoR). Many in this latter group received funding and
      administrative support and advice from ELENoR in order to prepare written
      submissions for assessment. Some sample loss was encountered within the pilot
      project, which was attributable largely to conflicting demands on participants'
      time. Indeed, the preparation of written submissions within the South West
      coincided with the introduction of primary care groups (PCGs) in April 1999,
      which several practices cited as having a major impact on their participation in
      the pilot project. A final sample of 15 practices (nine in the South West and six
      through ELENoR) underwent assessment through the pilot project. EVALUATION: A
      formal evaluation of the Primary Care Research Team Assessment (PCRTA) pilot was
      undertaken by an independent researcher (FM). This was supplemented with feedback
      from the assessment team members. The qualitative aspect of the evaluation, which
      included face-to-face and telephone interviews with assessors, lead researchers
      and other practice staff within the pilot research practices, as well as members
      of the project management group, demonstrated a positive view of the pilot
      scheme. Several key areas were identified in relation to particular strengths of
      research practices and areas for development including: Strengths Level II
      practices were found to have a strong primary care team ethos in research. Level
      II practices tended to have a greater degree of strategic thinking in relation to
      research. Development areas Level I practices were found to lack a clear and
      explicit research strategy. Practices at both levels had scope to develop their
      communication processes for dissemination of research and also for patient
      involvement. Practices at both levels needed mechanisms for supporting
      professional development in research methodology. The evaluation demonstrated
      that practices felt that they had gained from their participation and assessors
      felt that the scheme had worked well. Some specific issues were raised by
      different respondents within the qualitative evaluation relating to consistency
      of interpretation of standards and also the possible overlap of the assessment
      scheme with other RCGP quality initiatives. NATIONAL IMPLEMENTATION OF THE
      PRIMARY CARE RESEARCH TEAM ASSESSMENT: The pilot project has been very successful
      and recommendations have been made to progress to a UK scheme. Management and
      review of the scheme will remain largely the same, with a few changes focusing on
      the assessment process and support for practices entering the scheme. Specific
      changes include: development of the support and mentoring role of the primary
      care research networks increased peer and external support and mentoring for
      research practices undergoing assessment development of assessor training in line
      with other schemes within the RCGP Assessment Network work to ensure consistency
      across RCGP accreditation schemes in relation to key criteria, thereby
      facilitating comparable assessment processes refinement of the definition of the
      two groups, with Level I practices referred to as Collaborators and Level II
      practices as Investigator-Led. The project has continued to generate much
      enthusiasm and support and continues to reflect current policy. Indeed, recent
      developments include the proposed new funding arrangements for primary care R&D,
      which refer to the RCGP assessment scheme and recognise it as a key component in
      the future R&D agenda. The assessment scheme will help primary care trusts (PCTs)
      and individual practices to prepare and demonstrate their approach to research
      governance in a systematic way. It will also provide a more explicit avenue for
      primary care trusts to explore local service and development priorities
      identified within health improvement programmes and the research priorities set
      nationally for the NHS.

PMID- 12049029
TI  - [Dengue in Cuba].

PMID- 12049030
TI  - Enhanced severity of secondary dengue-2 infections: death rates in 1981 and 1997
      Cuban outbreaks.
AB  - OBJECTIVE: To understand the possible effect that length of time has on disease
      severity with sequential dengue infections. METHODS: Death and hospitalization
      rates for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) per 10,000
      secondary dengue-2 infections were compared in the same age group for two dengue
      2 (DEN-2) epidemics in Cuba. The first DEN-2 epidemic affected all of Cuba in
      1981; the second one, in 1997, impacted only the city of Santiago de Cuba. The
      sensitizing infection for DHF/DSS for each of the DEN-2 epidemics was dengue-1
      (DEN-1) serotype virus, which was transmitted in 1977-1979, that is, 4 years and
      20 years before the two DEN-2 epidemics. Using published seroepidemiological data
      from the cities of Havana and Santiago de Cuba, we estimated the rates at which
      persons aged 15-39 years old and those 40 years and older were hospitalized or
      died of DHF/DSS in Havana and in all of Cuba in 1981 and in just Santiago de Cuba
      in 1997. RESULTS: Among adults 15-39 years old the death rate per 10,000
      secondary DEN-2 infections was 38.5 times as high in Santiago de Cuba in 1997 as
      in Havana in 1981. As a further indication of the increased severity coming with
      a longer period between the initial DEN-1 infection and the secondary DEN-2
      infection, the case fatality rate for that same age group was 4.7 times as high
      in Santiago in 1997 as it was in Havana in 1981. CONCLUSION: We found a marked
      increase in severity with the longer of the two intervals (20 years) between an
      initial DEN-1 infection and a secondary DEN-2 infection. Such a difference may be
      due to subtle shifts in causative dengue strains or to changes with the passage
      of time in the circulating population of human dengue antibodies. These
      observations have important implications for dengue control, pathogenic
      mechanisms, and vaccine development.

PMID- 12049032
TI  - [Malaria control in Brazil: 1965 to 2001].
AB  - This paper reviews malaria control initiatives in Brazil, from the Malaria
      Eradication Campaign (Campanha de Erradicacao da Malaria), which was launched in
      1965 and was based on spraying dichlorodiphenyltrichloroethane (DDT) and on
      administering antimalarial drugs, to the implementation, in 2000, of the Program
      for Intensification of Malaria Control in the nine-state Legal Amazon region of
      Brazil (Plano de Intensificacao das Acoes de Controle da Malaria na Amazonia
      Legal), which was implemented in response to the World Health Organization's Roll
      Back Malaria effort. Among the Brazilian initiatives discussed are
      epidemiological stratification, the Impact Operation (Operacao Impacto), the
      Amazon Basin Malaria Control Project (Projeto de Controle da Malaria na Bacia
      Amazonica), and the Integrated Malaria Control Program (Programa de Controle
      Integrado da Malaria). Although there was progress in the control of malaria
      before the Intensification Program was launched in 2000, the actions carried out
      were not sustained. From 1998 to 1999 there was even a 34% increase in the number
      of malaria cases in the Brazilian Amazon. The Intensification Program set a goal,
      in comparison to 1999, of reducing by 50% the number of malaria cases by the end
      of 2001 and of cutting by 50% the mortality due to malaria by the end of 2002.
      Data for 2001 showed an overall 39% decrease in the number of malaria cases in
      the nine Amazonian states of the Intensification Program. The smallest decrease
      (15%) was in the state of Amapa, where the plan was not implemented until the
      second half of 2001. In terms of incidence by species, there was a 35% reduction
      in cases caused by Plasmodium falciparum and a 41% reduction in cases caused by
      P. vivax. The only independent variable that explains this reduction is the
      implementation of the Intensification Program. Although preliminary, these
      results indicate considerable gains. Decisive to this progress has been the
      strong mobilization of federal, state, and municipal governments.

PMID- 12049031
TI  - [Developing and using a PCR test to detect subclinical Mycobacterium leprae
      infection].
AB  - OBJECTIVE: While the prevalence of leprosy has declined around the world, there
      has not been a corresponding decrease in its incidence, thus indicating that it
      has not been possible to prevent transmission of the disease. Despite the small
      number of patients with lepromatous leprosy, the majority of the inhabitants of
      endemic areas show signs of exposure to Mycobacterium leprae, which could be
      explained by the presence of subclinical bacilliferous infections in the
      community. The objective of this study was to investigate the use of a polymerase
      chain reaction (PCR) test to detect M. leprae in samples of nasal mucus from
      asymptomatic household contacts of patients with leprosy. METHODS: We
      standardized and optimized a PCR technique to amplify a 321 base pair DNA
      fragment, using a pair of primers complementary to a segment of an LSR/A15 gene
      that codes for the 15 kDa M. leprae antigen. We investigated the optimal
      concentrations of all the test components. We used dimethyl sulfoxide (DMSO) to
      achieve a more specific amplification. We applied the PCR test to 70 healthy
      household contacts of leprosy patients from eight municipalities in Colombia
      where there was a high prevalence of the disease. RESULTS: The test's detection
      limit was 100 fg of DNA. With the optimized technique, bacillus was detected in
      the nasal mucus samples of 9 (12.8%) of the 70 household contacts. The 3 PCR
      positive household contacts of paucibacillary cases were from municipalities with
      very high prevalence levels. In comparison to contacts who were PCR-negative, the
      contacts who were PCR-positive had spent significantly less time, as a proportion
      of their age, living with a patient (P = 0.028). This finding demonstrates the
      test's capacity for early detection. CONCLUSIONS: The PCR test that we developed
      is useful as a tool for detection and early follow-up of possible leprosy cases.
      It can be used to monitor high-risk populations and also to maintain the
      achievements of leprosy elimination programs in countries where the disease's
      prevalence has been significantly reduced.

PMID- 12049033
TI  - Traveler's diarrhea: epidemiology and impact on visitors to Fortaleza, Brazil.
AB  - OBJECTIVE: To assess the epidemiology and impact of traveler's diarrhea (TD)
      among visitors to the city of Fortaleza, Ceara, Brazil, as part of a global study
      on TD carried out in four countries. METHODS: Within a cross-sectional survey,
      questionnaires were completed by departing travelers at the Fortaleza airport
      between March 1997 and February 1998. The questions inquired about demographics,
      duration of stay, reason for their visit, pretravel health advice they had
      received, risky food and beverage consumption while in Fortaleza, and quality of
      life during the visit to Fortaleza in relation to having or not having contracted
      TD. RESULTS: A total of 12,499 questionnaires were analyzed. The most common
      reason that the visitors gave for their travel to Fortaleza was a holiday
      (60.3%). The total diarrhea attack rate was 13.4%. Younger people (< 36 years)
      had significantly higher TD attack rates than did older persons. Using a logistic
      regression model, we investigated the visitors' risk factors, including age,
      gender, length of stay, and trip's purpose. According to that analysis,
      characteristics that are slightly predictive of TD are gender, length of stay,
      and visiting as a tourist rather than for some other purpose. Characteristics
      that protect against contracting TD include being older and traveling for
      business rather than for some other reason. Of those who were incapacitated by
      TD, the mean duration of the impairment was 42 hours. CONCLUSIONS: TD affected
      the travel plans and activities of many of the visitors to Fortaleza. Further,
      although aware of the health risks, the majority of those travelers did not avoid
      all potentially contaminated food or beverage items. Given this pattern of
      behavior, future efforts to combat TD may have to depend on such other
      alternative strategies as new vaccines.

PMID- 12049034
TI  - [Home hospitalization in light of demographic changes and new health challenges].
AB  - OBJECTIVE: Today, the most important demographic change taking place is the rapid
      aging of the population. While this phenomenon is having a growing and profound
      impact on all spheres of society, its greatest impact is in the health area,
      affecting all levels of health care and leading to the need for new resources and
      new structures. Out of that, in many countries have come different alternatives
      as well as in-patient, outpatient, and in-home programs that are geared toward
      improving health care and helping set priorities. One of these new initiatives is
      home hospitalization, or home health care. One objective of this study was to
      describe and analyze the characteristics of a population in Spain that was
      assisted through home hospitalization (HH). Another objective of the study was to
      comment on the role that HH can play as a mechanism for integration and
      coordination between health care levels, in the face of the challenges occurring
      with the reorganization of health care policies and programs, especially those
      directed at the elderly. METHODS: A retrospective descriptive study was done of
      patients assisted through HH in Sanitary Area 9 of the Autonomous Community of
      Valencia, which is on the eastern coast of Spain. The area's population was
      321,361, of whom 60,079 (18.7%) were 60 or older, including 43,044 (13.4%) who
      were 65 or older. A descriptive study of the analyzed variables was done, with
      the mean and standard deviation being computed for quantitative variables, and
      the absolute and relative frequencies (percentages) being calculated for the
      qualitative variables. RESULTS: Of the patients studied, 78% of them were 65 or
      older, with an average age of 73 years. They were predominantly women. Of the
      total group, 72% of them had chronic diseases, and 67% had at least one
      associated secondary diagnosis. There was an important problem of communication
      between the two principal levels of care, primary care and hospital care, which
      obviously had an impact on the patients and on the quality and effectiveness of
      their health care. Furthermore, it was found that HH finds its greatest utility
      with and is an effective tool for an adult or elderly population that has
      multiple chronic degenerative or terminal diseases. CONCLUSIONS: The results of
      this study highlight the need to create or strengthen channels and mechanisms for
      interinstitutional communication that will guarantee continuity of care. The
      ongoing, effective care of the health and well-being of elderly persons requires
      different levels of health interventions. This care should be comprehensive,
      adequate, integrated, of high quality, humanized, timely, and coordinated between
      the two principal levels of health care. In the final analysis, these factors
      will determine the quality of the health care for geriatric patients and the
      capacity to solve their health problems.

PMID- 12049035
TI  - [Accelerated rubella control and the prevention of congenital rubella syndrome].
AB  - Congenital rubella syndrome (CRS) is associated with substantial morbidity and
      mortality and with high costs. Today, as a result of improved vaccination and
      epidemiological surveillance efforts directed at eradicating measles from the
      Western Hemisphere, there has been a notable increase in the ability to detect,
      prevent, and control rubella and CRS. The importance of these measures is
      undeniable, and this piece examines the components that are essential in moving
      ahead to reduce these major public health problems in Latin America and the
      Caribbean. One step in that direction would be to integrate the surveillance of
      measles with that of rubella and CRS.

PMID- 12049036
TI  - [How do we heal the Argentine health care system?].
AB  - This article proposes a set of measures to reform the Argentine health care
      system and turn the country's current crisis into an opportunity for progressive,
      sustainable change. The proposal consists of a model for the intergovernmental
      division of health responsibilities. The national government would be responsible
      for strengthening its leadership role and for developing national insurance for
      low-prevalence high-cost diseases. With the provincial governments, the insurance
      role would be strengthened, with public health insurance making certain that
      there is universal coverage. Public hospitals would function as autonomous
      entities financed by social insurance, private insurance, and provincial public
      insurance. Municipalities would have an active role in disease prevention and
      health promotion, principally through primary care.

PMID- 12049037
TI  - Congratulations on materials on the surveillance of noncommunicable diseases.

PMID- 12049038
TI  - The coverage the Arkansas Medical Society has afforded the issue of mental
      illness.

PMID- 12049039
TI  - Casualties of war. Patients are biggest victims in era of malpractice.

PMID- 12049040
TI  - Secondary cardiovascular disease prevention.

PMID- 12049041
TI  - Ultrasound findings in a patient with primary orbital hemangiopericytoma.
AB  - A 20-year-old white male with a left superorbital mass and significant left
      proptosis was referred from his primary care physician. A and B scan ultrasound
      examination revealed a mass in the superonasal quadrant of the left orbit that
      demonstrated compression, encapsulation, internal vascularity and low internal
      reflectivity. Diagnosis of orbital hemangiopericytoma was confirmed
      histologically from frozen sections taken during surgical excision of the tumor.

PMID- 12049042
TI  - Medical students and surgical education: a resident's perspective.
AB  - Our current system of surgical education can be traced directly to the program
      developed by Halsted near the turn of the century. Modern medical education also
      can trace its roots to the early 20th century, when the "Flexner Report"
      radically changed the way doctors were trained in America. Today, multiple
      modalities can be used in resident and student education: case/problem-based
      learning, patient-based learning, traditional didactic lectures and standardized
      patients. As residents, we are charged with the daunting tasks of not only
      learning the art of surgery ourselves, but teaching medical students. Surgical
      residents have a unique opportunity to make an impression on medical students
      that can last a lifetime. For the vast majority of students, their junior year
      surgical clerkships will be their only exposures to surgical principles. It is
      the resident's responsibility to maximize this limited time; hopefully he'll make
      it the most enjoyable rotation of the student's third year.

PMID- 12049043
TI  - The UAMS College of Public Health: an early report on structure and function.
AB  - The UAMS College of Public Health has pulled together an initial faculty from
      across the state to launch its new public health curriculum. Forty-three students
      are enrolled in a program that is committed to community-based education and to
      health policy formulation for Arkansas. Partnerships are being developed and
      collaboration is ongoing with the Arkansas Medical Society, several universities
      and a number of health agencies and organizations to move the college forward in
      its vision of "optimal health for all."

PMID- 12049044
TI  - [Experience of a nursing student in an interdisciplinary team: factory of ideas].
AB  - The experience of the Curricular Training in a mental health work attendance to
      out-patients, CAPS, lead to this study development in the attempt to understand
      and characterize interdisciplinary team in this institution, as well as to
      understand the admittance of a nursing student in this team. The analysis of the
      replies disclosed that in the reports is found the concept of interdiscipline as
      well as of the multidiscipline (work in compartments). The conception which has
      of the model of assistance and of the admittance of the project in it is
      compatible with the conceptions that establish the description of the work:
      flexibility, the projects inter-relation the enlarged practice and the
      psychosocial rehabilitation. The fact that the service has a Program of lecturing
      -Assistance Integration, "naturalizes" and validates the participation of a
      nursing student in the projects of assistance or sociability.

PMID- 12049045
TI  - [Suffering in laryngeal cancer].
AB  - With the purpose of improving the care of laryngectomized patients, the aim is to
      understand the illness experience of patients and families of having larynx
      cancer. The participants were 14 laryngectomized patients and their families, in
      different post-surgical periods. The narrative analysis searched for categories
      which were understood on the basis of an anthropological focusing the culture.
      The understanding that the participants had of the illness experience of having a
      larynx cancer shows us that this process is one of suffering, of searching of
      strategies of coping, of evaluating the survival to the surgical treatment, which
      were based on the cultural system, which is different from the biomedical model
      of the health professionals and they must be considered in the approach for the
      rehabilitation.

PMID- 12049046
TI  - [The use of focal groups as qualitative method in health promotion].
AB  - The present work aims at demonstrating the importance of application of a quality
      research technique for health awareness. Such technique, called focus group, can
      be widely applied because of its low cost and also because it enables a fast
      diagnosis. Use complement information supplied by the community, know attitudes,
      points of view, perceptions and behaviors related to health, in order to develop
      programs and evaluates audiovisual tools. The application of this methodology has
      proven very effective for diagnoses and events on Health Awareness, according to
      experiments already carried out by the authors, which will be reported.

PMID- 12049047
TI  - [Functional method in nursing practice approached through group dynamics: our
      experience].
AB  - This study discusses the functional method applied to Nursing, approached through
      a group dynamics developed with three groups of Master students from the
      University of Sao Paulo at Ribeirao Preto College of Nursing. After the dynamics,
      the subjects answered a questionnaire with four questions. The responses of the
      first group showed the limitations of the functional model that interfere in the
      work such as: impersonal relationships, fragmentation of tasks, centralization of
      decisions causing the workers' dissatisfaction. The groups II and III pointed out
      some advantages when the work is based on a team, such as the exchange of
      experiences, participant planning and shared decisions, resulting in satisfaction
      at work.

PMID- 12049048
TI  - [Classification of nursing interventions].
AB  - During the last years, Nursing is seeking to classify its diagnoses,
      interventions/actions and outcomes. Here is presented one of the classifications
      of nursing interventions that was proposed by nurses of the University of Iowa in
      1987, the Nursing Interventions Classifications (NIC) as well as the reasons os
      its creation, in order to contribute to the dissemination of one of the most
      advanced proposals for classifying nursing interventions.

PMID- 12049049
TI  - [Surgery suspension: attitudes and representations of nurses].
AB  - The present work make considerations about the nurses social representation of
      surgery suspension and their attitudes in front of the problem. The dates was
      collected through interviews whit thematic guide and later categorization of
      attitudes in front of the problem. By the analysis of the contents verbalized by
      nurses it was used the theoretical background of the Social Representations. The
      results was systematized in a Attitude Scale that varied from Passivity with
      persistence of cultural traces of submission, like a traditional form of working,
      to Active Actions, with autonomy, destined to resolve the problem of surgery
      suspension or reduced its consequences.

PMID- 12049050
TI  - [Caring of the mental patient in the emergency room: feelings and attitudes of
      the nursing team members].
AB  - This work is based upon a day-by-day study of the services provide by a nurse
      team at a mentally impaired emergency room. Our aim is to study staff's reactions
      toward the patients as well as service itself. We could feel the dynamic relation
      among thinking, feeling and performance created strong conceptions on individuals
      based upon a common sense. The feelings noticed are: pity, scare and rage
      depending upon behavior. The assistance given to the mentally impaired is, at
      large, based exclusively on technical data resorted to organic/biological
      aspects.

PMID- 12049051
TI  - [Sexuality covered by the body's silence].
AB  - The humane relations are mediated by the verbal and non-verbal communication. The
      non-verbal communication expresses our feelings and emotions, it complements,
      contradicts and replaces the verbal communication. This study reflects upon the
      non-verbal communication as a specific approach to sexuality covered by the
      bodies silence and it expresses the feelings which are determined by the
      interrelation process of each experience. The data were collected through
      individual interviews realized from January to March by the year 1995, according
      to the women from a countryside area in Rio Grande do Sul. It is included in this
      study the non-verbal signs of the "paralanguage", body language, touch language,
      and also clothes and items demonstrating the culture, value and cultural
      preconceptions about Sexuality.

PMID- 12049052
TI  - [Work accidents among nursing workers at a university hospital].
AB  - A descriptive study was conducted to assess the epidemiological aspects of the
      work accidents that occur among nursing personnel. The study consisted of a
      population of 1,218 workers and assessed 100 accidents, that corresponded to 8.2%
      of all accidents that took place during the period, January 1st 1995 to June 3rd
      1995. The summary of this study evaluates the work accidents that occur among
      these nursing personnel and the risk factors presented by the working conditions
      of a university hospital.

PMID- 12049053
TI  - [Ethnography: methodologic strategy used to conceptualize the cultural scenario
      in an intensive care center at a university hospital].
AB  - This work is a part of an ethnographic study accomplished in a university
      hospital ICC that had as objective to describe the intensive care workers'
      culture. It is presented cultural domains a taxonomies developed from the
      workers' narration The results here presented show that ethnography is a
      methodological strategy appropriate for a cultural background contexture from a
      viewpoint of those who experiment the everyday intensive care work.

PMID- 12049054
TI  - [Trying to preserve the integrity of the family unit: the family living with the
      experience of having a child in the pediatric intensive care unit].
AB  - The purposes of this study were to: understand the dynamic functioning of the
      family with a child admitted to a pediatric intensive care unit (PICU) and to
      construct a theoretical model about the living experience of a family with a
      child admitted to the PICU. The study used as a theoretical reference the
      Symbolic Interactionism, and the Grounded theory methodology. The comparative
      analysis of the data permitted identify two phenomena: Having a family rupture
      and Living with the possibility of loosing a child. The relationship of these
      phenomena has permitted the identification of the core category TRYING TO
      PRESERVE THE INTEGRITY OF THE FAMILY UNIT based on which it was possible to
      propose a theoretical model to explain the experience.

PMID- 12049055
TI  - [Control of the postoperative pain].
AB  - The pain is a frequent symptom during the postoperative period and results in
      suffering and unnecessary risks for the patient. Studies show the inadequate pain
      relief after surgery and the relationship with erroneous assessment and non
      acquaintance about analgesics methods. The article discuss the postoperative pain
      management which includes the use of nonsteroidal antiinflammatory drugs,
      opioids, cognitive-behavior interventions and high-tech like epidural catheter
      and patient-controlled analgesia systems. Besides the adequate pain control
      includes the discussion about ethical and economic aspects.

PMID- 12049058
TI  - New York Academy of Dentistry Member Directory.

PMID- 12049056
TI  - [Use of paraformaldehyde tablets by Brazilian health institutions -- Part I].
AB  - A national survey was accomplished next to 6907 health Institutions through a
      questionnaire to explore and to describe the use of Parafolmaldehyde Tablets as
      microbicide agent. There was a return of 443 (6.41%) correspondences which 253
      (57.89%) affirmed to apply this chemical agent. Several articles of medical
      hospitable use with indication to sterilization through autoclaves, are processed
      by Parafolmaldehyde Tablets in the researched Institutions, demonstrating
      inadequate criteria in choosing the process. Another detected inadequate use of
      Parafolmaldehyde Tablets was in the processing of articles with lumens and the
      density materials due to the low penetrability of the gas. The nurses' perception
      with reference to the perspectives of Parafolmaldehyde Tablets's use as
      sterilizing chemical agent, in environmental conditions is of disuse, pointing
      for a search of safer technologies.

PMID- 12049059
TI  - APA policy on clinical and environmental factors contributing to antibiotic
      resistant bacteria. Ambulatory Pediatrics Association.

PMID- 12049060
TI  - Re: Phelan KJ, et al. Trends and patterns of playground injuries in United States
      children and adolescents. Ambulatory Pediatrics 2001;1:227-233.

PMID- 12049061
TI  - 50 years and 50 pearls.

PMID- 12049062
TI  - Chlorhexidine.
AB  - Chlorhexidine remains the gold standard to which other antiplaque and gingivitis
      agents are compared. Its effectiveness can be attributed to it bactericidal and
      bacteriostatic effects and its substantivity within the oral cavity. While other
      agents may possess one or more of these properties, few possess all three and
      perform so well. The antimicrobial properties of chlorhexidine are attributed to
      it di-cationic structure, and it is this same property that is the basis of its
      most common side effect, extrinsic tooth staining. By understanding the
      biochemical properties of chlorhexidine, an appreciation for the efficacy and use
      of chlorhexidine can be developed. It is only in such a way that the efficacy can
      be maximized and the side effects minimized, allowing chlorhexidine to remain the
      gold standard.

PMID- 12049063
TI  - [Highlights from CROI 2002. Individualized therapy for promoting adherence].

PMID- 12049065
TI  - Fermentation, phlogiston and matter theory: chemistry and natural philosophy in
      Georg Ernst Stahl's Zymotechnia Fundamentalis.
AB  - This paper examines Georg Ernst Stahl's first book, the Zymotechnia
      Fundamentalis, in the context of contemporary natural philosophy and the author's
      career. I argue that the Zymotechnia was a mechanical theory of fermentation
      written consciously against the influential "fermentational program" of Joan
      Baptista van Helmont and especially Thomas Willis, Stahl's theory of fermentation
      introduced his first conception of phlogiston, which was in part a corpuscular
      transformation of the Paracelsian sulphur principle. Meanwhile some assumptions
      underlying this theory, such as the composition of matter, the absolute passivity
      of matter and the "passions" of sulphur, reveal the combined scholastic and
      mechanistic character of Stahl's natural philosophy. In the conclusion I show
      that Stahl's theory of fermentation undermined the old fermentational program and
      paved the way for his dualist vitalism.

PMID- 12049064
TI  - Preventing osteoporosis: outcomes of the Australian Fracture Prevention Summit.

PMID- 12049066
TI  - The GTZ-SEAMEO-UPM/CPH Partnership (1982-1998).

PMID- 12049067
TI  - Distance education at the postgraduate level: responding to national health human
      resource needs.

PMID- 12049069
TI  - Abstracts of the 35th Annual Meeting of the Society for Epidemiologic Research.
      Palm Desert, California, USA. June 18-21, 2002.

PMID- 12049070
TI  - Abstracts of the 62nd Annual Meeting of the American Diabetes Association. San
      Francisco, California, USA. June 14-18, 2002.

PMID- 12049071
TI  - Abstracts of the 47th Annual Meeting of the Health Physics Society. 16-20 June
      2002. Tampa, Florida, USA.

PMID- 12049072
TI  - Practice parameter on laboratory panel testing for screening and case finding in
      asymptomatic adults. Laboratory Testing Strategy Task Force of the College of
      American Pathologists.

PMID- 12049073
TI  - Eruption process of upper permanent canine.
AB  - The purpose of this study was to investigate normal eruptive pattern of upper
      permanent canine. One hundred and fifty-one panoramic radiographs were used.
      Inclination of upper canine and lateral incisor, length and horizontal and
      vertical positions of cusp and root apex of the canine were evaluated. The canine
      erupted with increasing distal inclination and with no significant changes of the
      lateral incisor. Developmental changes of the canines relative to palatal plane
      and midline were shown by figures.

PMID- 12049074
TI  - Eruption disturbances of mandibular permanent incisors.
AB  - In this study, we analyzed 7 eruption disturbance cases of mandibular permanent
      incisors (5 males and 2 females), aged 5y9m to 10y4m. The etiology was divided
      into 3 categories: traumatic injuries (3 cases), odontomas (2 cases),
      supernumerary teeth (2 cases). The procedures such as removal of cause (4 cases),
      surgical exposure (5 cases) and traction (1 case) were done.

PMID- 12049076
TI  - The relationship between occlusal factors and bruxism in permanent and mixed
      dentition in Turkish children.
AB  - The aim of this study was to investigate the relationship between occlusal
      factors (overjet, overbite, Angle's Classification of molars and cuspids, the
      relationship of the primary molars, openbite, lateral openbite, scissorbite and
      crossbite) and bruxism in permanent and mixed dentition in Turkish children. For
      this reason 182 children with mixed dentition and 212 children with permanent
      dentition were included in this study. Occlusal conditions were examined
      clinically and bruxism was assessed by using interview and questionnaires. Z Test
      was used to compare the results. It was found that in both dentitions some
      occlusal factors related with bruxism (overjet > 6 mm, overbite > 5 mm, negative
      overjet, openbite in permanent dentition; overjet > 6 mm, overbite > 5 mm,
      scissorbite, anterior-posterior multiple teeth crossbite, Angle Class I occlusion
      in mixed dentition.

PMID- 12049068
TI  - Guidelines for the management of oesophageal and gastric cancer.

PMID- 12049075
TI  - Clinical management of ectodermal dysplasia with long term follow up: two case
      reports.
AB  - The present study describes the characteristics and clinical management of two
      patients with ectodermal dysplasia with long term follow-up. Dental treatments
      depend on the severity of disorder, therefore, treatment varies according to the
      age, growth and development of the stomatognathic system of the patient. It is
      important that the patient and dentist understand continued monitoring for dental
      problems is necessary. This provides improved aesthetics, function and emotional
      development.

PMID- 12049077
TI  - Clinical evaluation of bonding techniques in crown fractures.
AB  - The technique of bonding fragments when dental fractures occur is a routine
      procedure. The objective of this investigation is to demonstrate the retention of
      the fragments bonded using a compound material according to the Simonsen
      technique. The most noteworthy conclusion is that this type of restoration lasts
      less than two years when in the mouth. For this reason other therapeutic options
      with better future expectations should be introduced.

PMID- 12049078
TI  - Early treatment of an intruded primary tooth: a case report.
AB  - The report is about a case of total intrusion of a deciduous central incisor
      involving a male patient of 14 months of age. Repositioning of the intruded tooth
      was performed 20 minutes after the trauma, followed by placement with sutures.
      Clinical and radiographic monitoring performed after 1, 2, 4, 9, and 13 months
      showed normal characteristics. We emphasize the development of preventive
      programs promoting parental awareness of the importance of looking for prompt
      care, resulting in a better prognosis.

PMID- 12049079
TI  - TMJ fractures in children: clinical management and follow-up.
AB  - The mandible is the facial structure that is the most affected by trauma and the
      most common fracture site is the condyle. New perspectives for this problem are
      due to the fact that often TMJ fractures in children are undiagnosed and
      consequently untreated. This becomes evident when growth disturbances show up a
      year or two later. These types of trauma must be focused not only as a cause of
      direct damage to osseous structures, but also of future disturbances of the
      dentofacial development. Three cases of particular significance for the requested
      therapeutic approach are reported.

PMID- 12049080
TI  - Riga-Fede disease: report of a case and review.
AB  - Self-mutilation of tongue is a type of self-injurious behavior. Ulcers of the
      lingual frenum in neonates with natal lower incisors are referred to as Riga-Fede
      disease. In this paper a case of Riga-Fede disease in a ten-month infant male
      with lower central incisors is reported. The ulcer resolved after the sharp
      incisal edges were smoothened and topical triameinolone was applied. As this
      lesion may be confused or associated with other serious disorders, a review of
      medical and dental literature was included.

PMID- 12049081
TI  - Use of EMLA: is it an injection free alternative?
AB  - This study was conducted to evaluate the use of Eutectic Mixture of Local
      Anesthetics (EMLA) for various clinical procedures such as extraction of the
      mobile primary teeth, root stumps as well as pulpal therapy procedures in the
      primary teeth. Thirty children in need of routine dental procedures were selected
      and procedures were done under a single anesthesia of EMLA. Pain perception and
      the effectiveness of anesthesia were evaluated with the Eland's color scale and
      Lickert's scale respectively. Results showed that use of EMLA could to some
      extent eliminate the use of the needle in the procedures performed especially in
      pediatric dentistry.

PMID- 12049082
TI  - Shear bond strength of six restorative materials.
AB  - The purpose of this study was to determine and compare the shear bond strength of
      a conventional glass-ionomer cement, a resin modified glass-ionomer, a composite
      resin and three compomer restorative materials. Dentin of the occlusal surfaces
      from sixty extracted human permanent molars were prepared for shear bond strength
      testing. The specimens were randomly divided into six groups of 10 each. Dentinal
      surfaces were treated according to the instructions of manufacturers for each
      material. Each restorative material was placed inside nylon cylinders 2 mm high
      with an internal diameter of 3 mm, which were placed perpendicular to dentin
      surfaces. Shear bond strengths were determined using an Universal Testing Machine
      at crosshead speed of 0.5 mm/min in a compression mode. Conventional glass
      ionomer, Ketac-Molar aplicap showed the lowest mean shear bond strength 3.77+/
      1.76 (X +/- SD MPa) and the composite resin, Heliomolar showed the highest mean
      shear bond strength 16.54+/-1.65 while the mean bond strength of Fuji II LC was
      9.55+/-1.06. The shear bond strengths of compomer restorative materials were
      12.83+/-1.42, 10.64+/-1.42 and 11.19+/-1.19 for Compoglass, Hytac and Dyract
      respectively. ANOVA revealed statistically significant differences in the mean
      shear bond strengths of all groups (P<0.001). No statistically significant
      difference was found between the three compomer materials (P>0.5). Ketac-Molar
      and composite resin showed statistically significant difference (P<0.0005). The
      mode of fracture varied between materials. It is concluded that the compomer
      restorative materials show higher shear bond strength than conventional glass
      ionomer and resin modified glass-ionomer, but less than composite resin. The
      fracture mode is not related to the shear bond strengths values.

PMID- 12049083
TI  - Posterior composite restorations in primary molars: an in vivo comparison of
      three restorative techniques.
AB  - This in vivo study evaluated the clinical performance of class II restorations,
      in primary molars after 12 months. Three restorative techniques were used:
      filling the cavities in bulk; filling with three horizontal increments and
      placement in three horizontal increments using pre-polymerized composite inserts.
      The composite resin used was Prisma TP.H (Caulk-Dentsply) with the adhesive
      system ScotchbondMultipurpose (3M). Initially 90 class II restorations were
      placed in 27 patients from 8 to 10 years of age and followed-up for 12 months.
      After this period 55 restorations were evaluated for anatomic form, color
      alterations at the margins, presence of decay and marginal adaptation. The
      results showed that all groups presented similar rates of wear, the bulk
      insertion technique showed better results for marginal adaptation, color
      alterations of the margins and less presence of caries at occlusal margins, and
      that composite resin TP.H could be used in class II restorations in primary
      molars.

PMID- 12049084
TI  - Efficacy of dentin adhesives in primary and permanent teeth.
AB  - The purpose of the present study was to investigate the efficacy of dentin
      adhesives and to examine acid resistance in primary and permanent teeth. The
      efficacy of dentin adhesives was evaluated by SEM observation and by measuring
      the wall-to-wall polymerization contraction gap and dentin hardness before and
      after conditioning. The detailed mechanism of dentin bonding was the same in both
      primary and permanent teeth.

PMID- 12049085
TI  - An unusual form of Actinomycosis of the mandible with a resultant gross sequester
      in a 4-year-old child: a case report.
AB  - Mandibular osteomyelitis due to Actinomyces group is considered rare in the
      pediatric population. The initial complaint of the 4-year-old child described
      here was increased swelling of his cheek and pain. The patient was managed
      successfully by surgical treatment with antibiotic therapy.

PMID- 12049086
TI  - Langerhans cell histiocytosis: recurrent lesions affecting mandible in a 10-year
      old patient.
AB  - Hand-Schuller-Christian disease is a multifocal variant of eosinophilic
      granuloma, characterised by the classical triad of bony lesions, exophthalmos and
      diabetes insipidus. This case relates recurrent Langerhans' cell histiocytosis
      lesions presented as destruction of periodontal support associated with diabetes
      in a 10-year-old patient. Medical history suggests that the case represents a
      case of Hand-Schuller Christian disease.

PMID- 12049087
TI  - Ameloblastic fibroma: a case report in a 6 year old.
AB  - A six-year-old boy was seen by his dentist for a tumor mass in the left
      mandibular region. The panograph revealed a multilocular radiotransparent lesion
      extending from the canine to the left mandibular ascending ramus with well
      defined borders. After biopsy, the lesion was enucleated via curettage of the
      bone bed. The lesion was diagnosed as ameloblastic fibroma. After six months,
      radiographs showed that the surgical defect had filled with new bone.

PMID- 12049089
TI  - Quiz page.   Light chain cast nephropathy with light chain deposition disease.

PMID- 12049088
TI  - Attention-deficit/hyperactive disorder: making a case for multidisciplinary
      management.
AB  - Attention Deficit/Hyperactivity Disorder (AD/HD) is characterized by a cluster of
      age-inappropriate behavioral abnormalities comprising inattentivity,
      hyperactivity and impulsivity. The definition is controversial and without an
      accurate diagnosis. Therefore, it seems prudent that a multidisciplinary
      treatment protocol should begin with non-drug psychological and behavioral
      strategies plus nutritional intervention.

PMID- 12049090
TI  - Grief: lessons from the past, visions for the future.
AB  - Over the last millennium, patterns of mortality have changed and have determined
      who grieves and how. At all times grief has been recognized as a threat to
      physical and mental health. More recently the scientific study of bereavement has
      enabled us to quantify such effects and to develop theoretical explanations for
      them. This article reviews our evolving understanding of grief, focusing
      especially on the developments in research, theory, and practice that have come
      about in the last century. Wars and similar conflicts are associated with
      repression of grief, but methods of helping by facilitating its expression that
      developed during the 2 World Wars are less needed and effective at other times.
      In recent years more attention has been paid to the social context in which grief
      arises and, particularly, to the nature of the attachments that precede and
      influence the reaction to bereavement and to other traumatic life events. At the
      same time a range of caring resources has become available and acceptable to
      bereaved people and the results of scientific evaluation of these gives promise
      that we are moving toward an era in which more sensitive and appropriate care
      will be provided to the bereaved by both voluntary and professional caregivers.

PMID- 12049091
TI  - Pulmonary function testing.

PMID- 12049092
TI  - Pediatric emergency medicine.

PMID- 12049094
TI  - New drug and biological drug products; evidence needed to demonstrate
      effectiveness of new drugs when human efficacy studies are not ethical or
      feasible. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its new drug and biological
      product regulations to allow appropriate studies in animals in certain cases to
      provide substantial evidence of the effectiveness of new drug and biological
      products used to reduce or prevent the toxicity of chemical, biological,
      radiological, or nuclear substances. This rule will apply when adequate and well
      controlled clinical studies in humans cannot be ethically conducted and field
      efficacy studies are not feasible. In these situations, certain new drug and
      biological products that are intended to reduce or prevent serious or life
      threatening conditions may be approved for marketing based on evidence of
      effectiveness derived from appropriate studies in animals and any additional
      supporting data.

PMID- 12049093
TI  - The bacteriorhodopsin gene.
AB  - The bacteriorhodopsin gene has been identified in a 5.3-kilobase restriction
      endonuclease fragment isolated from Halobacterium halobium DNA, using a cloned
      cDNA fragment as the probe. Of the 1229 nucleotides whose sequence was determined
      in the genomic fragment, 786 correspond to the structural gene of
      bacteriorhodopsin, 360 are upstream from the initiator methionine codon, and 83
      are downstream from the COOH terminus. The bacteriorhodopsin gene codes for a
      precursor sequence of 13 amino acids at the NH2 terminus, 248 amino acids that
      are present in the mature protein and an additional aspartic acid at the COOH
      terminus. This determination of the DNA sequence for an archaebacterial gene
      reveals that the standard genetic code is used; however, there is a marked
      preference for either G or C in the third codon position. The gene does not
      contain any intervening sequences and no prokaryotic promoter can be identified
      in the region immediately upstream from the structural gene. The
      bacteriorhodopsin mRNA contains at the 5' terminus only three nucleotides beyond
      the initiating AUG codon and this terminus can form a hairpin structure.
      Immediately downstream from this structure there is a sequence complementary to
      the 3' terminus of H. halobium 16S rRNA.

PMID- 12049095
TI  - Health insurance reform: standard unique employer indentifier. Final rule.
AB  - This final rule establishes a standard for a unique employer identifier and
      requirements concerning its use by health plans, health care clearinghouses, and
      health care providers. The health plans, health care clearinghouses, and health
      care providers must use the identifier, among other uses, in connection with
      certain electronic transactions. The use of this identifier will improve the
      Medicare and Medicaid programs, and other Federal health programs and private
      health programs, and the effectiveness and efficiency of the health care industry
      in general, by simplifying the administration of the system and enabling the
      efficient electronic transmission of certain health information. It will
      implement some of the requirements of the Administrative Simplification subtitle
      of the Health Insurance Portability and Accountability Act of 1996.

PMID- 12049096
TI  - Analysis and the hierarchy of nature in eighteenth-century chemistry.
AB  - What was the impact of Lavoisier's new elementary chemical analysis on the
      conception and practice of chemistry in the vegetable kingdom at the end of the
      eighteenth century? I examine how this elementary analysis relates both to more
      traditional plant analysis and to philosophical and mathematical concepts of
      analysis of current in the Enlightenment. Thus I explore the relationship between
      algebra, Condillac's philosophy and Lavoisier's chemical system as well as
      comparing Lavoisier's analytical approach to those of his predecessors, such as
      Baume and Bucquet. With reference to the aims of vegetable analysis, I show how
      the dominance of elementary analysis devalued a tradition that sought to isolate
      immediate principles (plant extracts), marginalizing the chemical practices of
      many doctors and pharmacists in the context of the new chemistry in France.

PMID- 12049097
TI  - Genetic screening of populations.

PMID- 12049098
TI  - Single mothers in California: understanding their health insurance coverage.

PMID- 12049099
TI  - Quality assurance of autopsy face sheet reporting, final autopsy report
      turnaround time, and autopsy rates: a College of American Pathologists Q-Probes
      study of 10003 autopsies from 418 institutions.
AB  - OBJECTIVE: To develop a multi-institutional reference database of autopsy
      practice and performance for quality improvement purposes. DESIGN: In 1990,
      participants in the Q-Probes quality improvement program of the College of
      American Pathologists (CAP) each retrospectively evaluated the 25 most recently
      completed consecutive autopsy reports and determined the number of deaths and
      autopsies that occurred in their institutions during 1989. SETTING: Hospital
      based autopsies excluding forensic cases and stillborn infants. PARTICIPANTS:
      Four hundred ten institutions in the United States and eight institutions in
      Canada. MAIN OUTCOME MEASURES: Completeness of face sheet information contained
      in final autopsy reports, turnaround time for completion of final reports, and
      institutional autopsy rates. RESULTS: In the aggregate database of 10003
      autopsies, the following six data items (from a total of 21) were present in 95%
      to 100% of the final autopsy reports in at least 85% of the participating
      institutions: institution where autopsy was performed, patient's name, patient's
      sex, autopsy number, autopsy date, and prosecter's name. The turnaround times for
      the final autopsy reports were as follows: 30 days or less in 47.6% of the cases,
      31 to 60 days in 28.8%, and more than 60 days in 23.7%. A higher median
      percentage of autopsy final reports were completed in 30 days or less in
      institutions with the following characteristics: nonteaching (P < .004), no
      pathology residency program (P < .002), and rural location (P < .027). A lower
      number of autopsies performed in 1989 was associated with a higher median
      percentage of final reports completed in 30 days or less (P < .007). The
      aggregate autopsy rate for all participating institutions was 12.4%, and the
      median rate was 8.3%. Median autopsy rates for teaching institutions and
      institutions with pathology residency training programs were 15% and 19%,
      respectively. CONCLUSIONS: This multi-institutional study identified a core group
      of face sheet data items that were consistently present on final autopsy reports.
      However, the majority of the face sheet data items examined were inconsistently
      recorded. Approximately 75% of final autopsy report turnaround times were within
      the standard established by the Joint Commission on Accreditation of Healthcare
      Organizations. Nearly two thirds of the institutions reported autopsy rates for
      1989 of 0% to 10%.

PMID- 12049100
TI  - Extraneous tissue in surgical pathology: a College of American Pathologists Q
      Probes study of 275 laboratories.
AB  - OBJECTIVE: To develop a multi-institutional reference database of extraneous
      tissue (contaminants) in surgical pathology. DESIGN: In 1994, participants in the
      College of American Pathologists Q-Probes quality improvement program performed
      prospective and retrospective evaluations of extraneous tissue found in surgical
      pathology microscopic sections for a period of 4 weeks or until 1000 slides were
      reviewed in each participating laboratory. PARTICIPANTS: Two hundred seventy-five
      surgical pathology laboratories institutions, predominantly from North America.
      MAIN OUTCOME MEASURES: Extraneous tissue contamination rate for slides in
      prospective and retrospective reviews; staffing and practice procedures; location
      of extraneous tissue on slides; type of extraneous tissue (normal, abnormal,
      nonneoplastic, neoplasm, microorganisms, etc); class of extraneous tissue (slide
      or block contaminants); source of extraneous tissue (different or same case);
      origin of extraneous tissue (pathology laboratory, physician's office or
      operating room); and degree of diagnostic difficulty caused by extraneous tissue.
      RESULTS: Three hundred twenty-one thousand seven hundred fifty-seven slides were
      reviewed in the prospective study and 57083 slides in the retrospective study.
      There was an overall extraneous tissue rate of 0.6% of slides (2074/321757) in
      the prospective study and 2.9% of slides (1653/57083) in the retrospective study.
      Of those slides with extraneous tissue, the extraneous tissue was located near
      diagnostic tissue sections in 59.5% of the slides reviewed prospectively and in
      25.3% of slides reviewed retrospectively; deeper sections were performed to
      evaluate extraneous tissue in 12.2% of prospective cases and in 3.1% of
      retrospective cases. Of the laboratories, 98% had written guidelines for changing
      solution in tissue processors, and 64.9% had guidelines for maintaining water
      baths free of extraneous tissue. A total of 98.9% used lens paper, filter bags,
      or sponges for processing fragmented and small specimens. Written protocols for
      documentation of extraneous tissue in surgical pathology reports were established
      in 6.1% of laboratories, for removal of extraneous tissue from blocks in 5.7%,
      and for removal of extraneous tissue from microscopic slides in 4.7%. In 24% of
      laboratories no comment or record was kept to document extraneous tissue.
      Extraneous tissue consisted of neoplasm in 12.7% of the prospectively reviewed
      slides and in 6.0% of the retrospectively reviewed slides. For the prospective
      study, 59.4% of extraneous tissue was classified as slide contaminants, and 28.4%
      was found to be contaminants within the paraffin block; for the retrospective
      study, 72.9% was classified as slide contaminants and 15.9% as block
      contaminants. For the prospective study, 63.2% of extraneous tissue was presumed
      to be from a different case, and in the retrospective study, 48.5% was presumed
      to be from a different case. Over 90% of extraneous tissue was thought to
      originate from the pathology laboratory. The degree of diagnostic difficulty
      caused by extraneous tissue was judged to be severe in 0.4% of slides in the
      prospective study and 0.1% of slides in the retrospective study. In the
      prospective study, it could not be determined whether the tissue in the
      diagnostic sections was extraneous in 0.6% of slides, and in the retrospective
      study, it could not be determined whether tissue in the diagnostic sections was
      extraneous in 0.1%. CONCLUSIONS: This study has documented the frequency, type,
      origin, source, and diagnostic difficulty of extraneous tissue and presents
      benchmarks of extraneous tissue experienced in the general practice of surgical
      pathology.

PMID- 12049101
TI  - Utility of micral test strips in screening for microalbuminuria.
AB  - OBJECTIVE: To evaluate the clinical utility of Micral strips for detection of
      microalbuminuria. DESIGN: One hundred three urine samples were tested by Micral
      strips for the presence of microalbuminuria, and the results were compared with
      the immunonephelometric method. SETTING: Endocrine diabetes clinic in a
      university-affiliated outpatient facility and the associated clinical laboratory.
      PATIENTS: Sixty-seven, 24-hour urine samples were obtained from 64 patients with
      diabetes. Thirty-six urine samples were obtained from normal controls; 22 of
      these were 24-hour samples and 14 were overnight samples. MAIN OUTCOME MEASURE:
      Concordance of results obtained by the two methods for the presence or absence of
      microalbuminuria. RESULTS: All 36 control subjects and 44 urine samples from
      diabetic patients had normal albumin excretion (<15 mg/24 h) by the
      immunonephelometric method. Seventy-eight of these were correctly identified as
      negative by Micral strips, giving a specificity of 97.5%. There were 23 samples
      with albumin excretion of more than 16 mg/24 h. Sixteen of these were correctly
      identified, giving a sensitivity of 69.5%. There were 16 samples with albumin
      excretion of 30 mg/24 h or more; 14 of these were correctly identified by Micral
      strips, and two were false negatives, giving a sensitivity of 87.7%. However,
      when urine samples with albumin concentrations of less than 11 mg/L were
      excluded, the Micral strips correctly read 21 out of 23 samples, giving a
      sensitivity of 91.3%. CONCLUSIONS: The specificity of Micral strips for detection
      of albuminuria in 24-hour urine samples is high (97.5%), but the sensitivity is
      low, ranging from 69.5% to 87.7%. The sensitivity was greatly improved when urine
      samples with albumin concentrations of less than 11 mg/L were excluded.

PMID- 12049102
TI  - Effect of off-site transportation on detection of Neisseria gonorrhoeae in
      endocervical specimens.
AB  - OBJECTIVES: To evaluate both the effect of off-site transportation on detection
      of Neisseria gonorrhoeae in cultured endocervical specimens and the impact of
      transportation on viability of N. gonorrhoeae by comparison of culture with a
      nucleic acid probe assay. DESIGN: Three endocervical swabs were randomly
      collected; one was tested on-site using a nucleic acid-based assay (PACE 2NG
      System, Gen-Probe, Inc, San Diego, Calif), one was tested off-site following
      inoculation to modified Thayer-Martin agar (Remel, Lenexa, Kan), and a third swab
      was tested on-site by culture isolation. A nucleic acid amplification assay of
      the original swab for PACE 2NG testing was used to resolve discrepancies.
      SETTING: The emergency department of a university medical center. PATIENTS: Four
      hundred two patients were evaluated. The test population consisted of both
      asymptomatic and symptomatic patients. MAIN OUTCOME MEASURE: Positivity for N.
      gonorrhoeae by one or more of the test procedures, with discrepancy analysis when
      warranted. RESULTS: Of 402 specimens evaluated, the sensitivities for on-site and
      off-site testing using culture isolation for N. gonorrhoeae were 88.9% and 77.8%,
      respectively, in a population prevalence of 6.7%. However, the sensitivity for on
      site PACE 2NG testing for N. gonorrhoeae was 96.3%. CONCLUSIONS: A decrease in
      sensitivity between on-site and off-site culture was found, which suggested
      transportation may have an adverse effect on the detection of N gonorrhoeae.
      However, with the limited population and prevalence, the difference was not found
      to be statistically significant. Further studies indicated that the nucleic acid
      probe assay was significantly more sensitive (P = .05) when compared with off
      site testing using a culture isolation method, demonstrating that viability is an
      important consideration. These results suggested that a molecular probe assay
      should be considered in testing specimens for N. gonorrhoeae, especially when the
      specimen is to be transported off-site.

PMID- 12049103
TI  - Uvitex 2B stain for the diagnosis of Isospora belli infections in patients with
      the acquired immunodeficiency syndrome.
AB  - OBJECTIVE: Fluorescent stains with Uvitex 2B or other fluorochromes are widely
      used today, especially for the diagnosis of microsporidian infections in human
      immunodeficiency virus (HIV)-infected patients. Our objective was to ascertain
      whether the fluorescent stain with Uvitex 2B is also able to detect Isospora
      belli in stool samples and duodenal/bile juice of HIV-infected patients. DESIGN:
      Case study. SETTING: University hospital of the University of Cologne, Germany.
      PATIENTS: Two HIV-infected patients with chronic diarrhea who had intestinal
      infections with I. belli. METHODS: Stool was concentrated by a modified water
      ether sedimentation method, and duodenal/bile juice was concentrated by
      centrifugation. Wet-mount preparations were examined by phase-contrast and bright
      field microscopy, and smears were stained with a modified acid-fast stain and a
      fluorescent stain with Uvitex 2B. RESULTS: Using the fluorescent stain with
      Uvitex 2B, the oocysts of I. belli stained bright white/blue fluorescent and
      showed a structure similar to that of the oocysts in acidfast stains.
      CONCLUSIONS: Staining with Uvitex 2B is a suitable method for the diagnosis of I.
      belli infections. This technique can be used for the diagnosis of three important
      gastrointestinal parasites (viz, microsporidia, cryptosporidia, and I. belli)
      responsible for diarrhea in HIV-infected patients.

PMID- 12049105
TI  - What is a juvenile polyp? An analysis based on 21 patients with solitary and
      multiple polyps.
AB  - BACKGROUND: Juvenile polyps, the most common pediatric gastrointestinal polyp,
      have been typically characterized as either hamartomatous overgrowths or reactive
      inflammatory proliferations. Recent observations of excessive colonic and gastric
      carcinoma and dysplasia in juvenile polyposis have prompted reclassification of
      this entity as a premalignant condition. The relationship between solitary or
      multiple juvenile polyps and malignancy is less clear. PATIENTS AND METHODS: To
      further investigate the frequency and significance of dysplasia in juvenile
      polyps, we analyzed 28 polyps from 21 patients histologically and
      immunohistochemically for substances previously associated with neoplastic
      transformation in the colorectal adenomacarcinoma sequence. RESULTS: Fifteen
      patients had a solitary polyp, two had 2 to 9 polyps, and four had polyposis with
      10 or more polyps. Most polyps exhibited inflammatory or regenerative atypia.
      Foci of dysplasia were noted in polyps from 11 patients, and immunoreactivity for
      p53 and human chorionic gonadotropin was present in 12 of the 28 polyps each.
      These findings were all more frequent in the polyposis specimens than in solitary
      polyps. CONCLUSIONS: These observations, in combination with reports of an
      increased risk of carcinoma in juvenile polyposis, suggest that juvenile polyps
      are lesions with a potential for neoplastic and malignant transformation,
      although they share features of an inflammatory reactive process. The
      implications for clinical management of patients and pathologic evaluation of
      juvenile polyps warrant further investigation.

PMID- 12049104
TI  - Development of a novel immunohistochemical staining technique (PLATESTAIN
      technique) based on the capillary action principle.
AB  - OBJECTIVE: To improve the complex manual staining methods used in
      immunohistochemistry, the authors invented a glass plate designed to achieve
      accurate immunoreaction using the capillary action principle. MATERIALS: This
      plate has slightly elevated edges and provides five narrow gaps between the
      reactive surfaces and glass slides. Each reactive surface is treated with a
      hydrophobic agent, to allow uniform antibody diffusion. RESULTS: Seventy-five
      cases of control tissues, benign neoplasms, and malignant neoplasms were
      immunohistochemically examined with this plate, and the staining intensity was
      compared with that of the conventional three-step streptavidin-biotin technique.
      Using this device and biotin-long spacer conjugated secondary antibody, even
      diffusion of antibodies and reagents and sensitive reactions could be achieved,
      thus making immunostaining easier and more accessible. The hydrophobic agent
      produced no unfavorable results. Also, the technique greatly reduced the amount
      of antibody, reagent, and chromogen solution required. Antigen retrieval by
      microwave heating of tissue sections and immunostaining of sex hormone receptors
      and cell proliferation markers were also successful. CONCLUSION: This technique
      provides a great technical improvement in immunohistochemistry and eliminates the
      health problems and environmental hazards associated with conventional
      techniques.

PMID- 12049106
TI  - Thyroglossal duct cysts: diagnostic criteria by fine-needle aspiration.
AB  - OBJECTIVE: To document the cytologic diagnostic criteria of fine-needle
      aspirations of thyroglossal cysts. DESIGN: Midline cervical masses were studied
      by fine-needle aspiration, and those 11 thyroglossal cysts that were resected
      served as a baseline for the evaluation of aspirates from 33 similar lesions that
      were not removed. SETTING: Physicians' offices, hospital outpatient clinics, and
      the aspiration service of a university department of pathology. PATIENTS: Forty
      four patients noting a mass in the anterior neck or found by physicians to have
      such a mass. INTERVENTIONS: Fifty-one aspirations (second aspirates in seven
      patients); surgical removal of the cysts in 11 patients. MAIN OUTCOME MEASURES:
      Aspirates were examined for cells, other particulate matter, and any
      extracellular material in the background. RESULTS: Smears from thyroglossal cysts
      are low in cellularity, and inflammatory cells are more numerous than epithelial
      cells. CONCLUSIONS: Fine-needle aspiration contributes to an accurate
      preoperative diagnosis of thyroglossal cysts, allowing a Sistrunk procedure to be
      performed in these patients rather than an inappropriate local resection.

PMID- 12049108
TI  - Giant cell fibroblastoma: a report of three cases with histologic and
      immunohistochemical evidence of a relationship to dermatofibrosarcoma
      protuberans.
AB  - PROBLEM CONSIDERED: Giant cell fibroblastoma (GCF) is a rare mesenchymal
      neoplasm, which is classified as a fibrohistiocytic tumor of intermediate
      malignancy owing to its propensity for local recurrence, although metastasis has
      not been documented. Prior reports have linked GCF to dermatofibrosarcoma
      protuberans (DFSP), given overlapping clinical and histologic features. METHODS:
      This report documents three additional cases of GCF that further support the
      contention that this lesion is histogenetically related to DFSP. RESULTS: All
      three lesions occurred on the trunk of patients whose ages were 4, 28, and 38
      years. One case that histologically resembled a GCF on initial excision recurred
      with areas of both GCF and DFSP. A second recurrence was composed entirely of
      DFSP. Another case contained areas of both GCF and DFSP, as well as a focus that
      was felt to be undergoing fibrosarcomatous change. The third case consisted
      entirely of GCF. Immunohistochemically, all three lesions showed intense
      immunoreactivity for CD34 in the GCF component. CD34 also strongly marked the
      cells in those cases with a DFSP component. CONCLUSIONS: Although GCF may not
      represent the "juvenile form" of DFSP, as previously suggested, the evidence
      strongly supports a histogenetic relationship between these two lesions, even
      though the cell of origin remains obscure.

PMID- 12049107
TI  - Portal amyloid: novel amyloid deposits in gastrointestinal veins?
AB  - OBJECTIVE: To specify uncharacterized amyloid deposits in gastrointestinal
      vessels of the elderly. MATERIALS AND METHODS: The gastrointestinal tracts from
      110 consecutive autopsies of individuals aged 85 years and older were examined
      for amyloid using Congo red staining. Immunohistochemical classification of the
      amyloid deposits was conducted using antisera directed against amyloid A,
      apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, apolipoprotein C-I,
      lysozyme, lambda and kappa light chain amyloid fibril proteins, transthyretin,
      beta2-microglobulin, and amyloid P component. Electron microscopic examination
      assessed the ultrastructural features. RESULTS: Thirty-eight (35%) of the 110
      cases had gastrointestinal amyloid deposits. In 17 cases the amyloid fibril
      proteins were defined immunohistochemically. In five cases (5%) the amyloid could
      not be classified because amyloid deposits were not present in the deeper serial
      sections used for immunohistochemistry. In 13 cases (11%) the vascular amyloid
      deposits could not be characterized because they did not demonstrate
      immunoreactivity with any of a panel of antibodies specific for the fibril
      proteins of all major extracerebral amyloids. In three individual cases, the
      vascular amyloid deposits showed variable immunoreactivity, with deposits being
      negative in some vessels. The immunohistochemically nonreactive vascular amyloid
      in these 16 cases had several consistent features: it affected only vessels of
      the small and large intestine, it was limited to mesenteric veins, it consisted
      of small dot- or comma-like deposits located in close proximity to fragmented
      elastic fibers, and it demonstrated inconsistent immunostaining for amyloid P
      component. CONCLUSIONS: The similar morphologic characteristics of nonreactive
      gastrointestinal amyloid deposits, which we have designated "portal amyloid,"
      suggest a common origin. Determination of whether portal amyloid represents a new
      type of amyloid will require chemical analysis.

PMID- 12049109
TI  - Benign breast aspirates: two decades of experience.
AB  - OBJECTIVE: To evaluate the reliability of benign breast aspirates. DESIGN: A 20
      year retrospective study of cytologically benign aspirates from palpable breast
      lesions followed by surgery and review of false negatives. RESULTS: Data
      encompassed 1518 benign aspirates followed by benign histology, and 99 by
      malignant histology. Of the latter, 89% underwent biopsy within 1 month. Review
      of 52 available false negatives revealed 10 (19%) with no change in the original
      diagnosis, 16 (31%) reviewed as unsatisfactory specimens, and 26 (50%) reviewed
      as specimens with focal cytologic atypia (dyshesion, nuclear enlargement, and
      contour irregularity). Cellularity (>20 epithelial groups per slide) was an
      important criterion in postmenopausal women. CONCLUSION: Our study confirms the
      reliability of benign breast aspirates interpreted in light of clinical and
      mammographic findings and demonstrates the importance of adequacy evaluation and
      focal atypia in preventing false negatives.

PMID- 12049110
TI  - P53 expression in choroid plexus neoplasms: an immunohistochemical study.
AB  - OBJECTIVE: To evaluate choroid plexus neoplasms for p53 expression. CASE
      MATERIAL: We studied 10 choroid plexus tumors (four papillomas and six
      carcinomas) by immunohistochemistry using the DO7 anti-p53 monoclonal antibody.
      RESULTS: Three of four choroid plexus papillomas demonstrated no staining.
      Scattered nuclear and rare cytoplasmic positivity was present in one papilloma,
      which showed foci of increased mitotic activity (labeling index 2.5%). Six of six
      carcinomas were immunoreactive for p53, and three cases had labeling indexes of
      over 70%. All immunopositive choroid plexus tumors (7/7) exhibited nuclear
      staining. Punctate cytoplasmic positivity was identified in 5 of 7 cases.
      CONCLUSION: Our study suggests that altered p53 expression is detectable by
      immunohistochemistry in choroid plexus neoplasms and is consistently present in
      choroid plexus carcinomas.

PMID- 12049111
TI  - Spindle cell carcinoma of the breast, a mimicker of benign lesions: case report
      and review of the literature.
AB  - The clinical and pathologic features of a breast tumor with unusual morphology in
      a 69-year-old woman are presented. Spindle cell carcinoma is considered one of
      the variants of metaplastic carcinoma and is commonly described in the upper
      aerodigestive tract, but it is relatively rare in the breast. This case is
      uniquely different from the usual cases of spindle cell carcinoma because of the
      lack of squamous differentiation or a recognizable infiltrating ductal component
      at the light microscopic level. With immunohistochemical stains using keratin and
      actin, a rather prominent network of infiltrating compressed ductal structures
      became apparent. These immunohistochemical features are consistent with the
      current concept of myoepithelial origin for metaplastic carcinomas. Although
      mention has been made in the literature of cases in which this "bland" carcinoma
      could be confused with benign nonneoplastic conditions, few illustrated examples
      exist. The prognosis for this particular subgroup of metaplastic carcinoma may be
      somewhat better than that for ordinary ductal carcinoma. For prognostic purposes,
      this entity should be distinguished from other metaplastic carcinomas and
      sarcomas, but more importantly, it should be differentiated from lesions such as
      nodular fasciitis, reactive granulation tissue, and fibromatosis, with which it
      may be confused histologically.

PMID- 12049112
TI  - Infarcted myxoid fibroadenoma following fine-needle aspiration.
AB  - Infarction of breast fibroadenomas is very rare and is frequently associated with
      physiologic changes, such as pregnancy and lactation. We report a case of an
      infarcted fibroadenoma following fine-needle aspiration. The patient presented
      with an asymptomatic breast mass, which was clinically difficult to evaluate.
      Excisional biopsy was performed 7 days after a nondiagnostic fine-needle
      aspiration of the mass. Microscopically, the nodule showed features of a classic
      fibroadenoma of the intracanalicular type with myxoid or mucinous stromal
      changes, as well as extensive areas of acute infarction. This report provides
      another example of the changes that may be observed in biopsy specimens obtained
      after fine-needle aspiration of the breast.

PMID- 12049114
TI  - Viability of autopsies outside the institutions.

PMID- 12049113
TI  - Pathologist's shoulder: microscopic disability and a light at the end of the
      scope.

PMID- 12049115
TI  - Blood culture quality improvement: a College of American Pathologists Q-Probes
      study involving 909 institutions and 289 572 blood culture sets.
AB  - OBJECTIVE: To evaluate solitary blood culture (SBC) collections as a preanalytic
      quality indicator of blood culture practice. DESIGN AND SETTING: Two College of
      American Pathologists Q-Probes laboratory quality improvement studies involving
      prospective evaluation of the proportion of and reasons for SBC collections in
      909 institutions. OUTCOME: Reduction in the proportion of SBCs. RESULTS: Of
      289572 blood culture sets studied, the median proportion of SBCs per institution
      was 10.1% and 12.1% among adult inpatients, 25.4% and 33.3% among adult
      outpatients, and 89.0% and 100% among pediatric/infant patients in the first and
      second (follow-up) studies, respectively. The two most common reasons for not
      performing a second culture in adults were (1) test not indicated and (2)
      physician believed one was sufficient. When compared with inpatient cultures, a
      significantly higher proportion of outpatient SBCs were classified as not
      indicated (P < .0001). Among 198 institutions participating in both studies, a
      significant decline in SBC rates was observed in the subgroup (n = 50) that
      continued to monitor SBCs (P = .004). CONCLUSIONS: Interinstitutional evaluation
      of solitary blood cultures provides a benchmark for quality assessment and an
      opportunity for performance improvement in blood culture specimen collections.

PMID- 12049116
TI  - Metal leachability from sewage sludge-amended Thai soils.
AB  - Determining mobility and availability of metals in sewage sludge amended soil is
      an environmental concern. Potential leachability and bioavailability of metals
      following sludge applied to agricultural soil was evaluated. Geochemical forms of
      metal occurring in sludge-amended soil were subjected to fractionation for
      understanding heavy metal transformation and remobilization in sludge-amended
      soil. Metal leachability was determined using reconstructed soil profiles where
      dewatered sewage sludge was incorporated into the surface 0-10 cm of soil. Two
      sludge application rates; 150 and 300 kgN/ha, equivalent to sludge at 4 and 8
      ton/ha, were applied to soil columns representing typical agricultural clay soils
      of Thailand (Rangsit acid sulfate soil). The soil columns were leached with 321
      equivalent to 600 mm of surface water using different leachants (distilled water
      pH 6, distilled water adjusted to pH 3 and rainwater pH 5). Among metals
      measurement, results showed Mn leachability from sludge-amended Rangsit soil were
      high at both sludge application rates (18-29% of total Mn applied). The
      leachability of other metals was less than 2.5 and 7.2% following application of
      150 and 300 kgN/ha of sludge, respectively. Results from the experiments
      indicated that the leachant at pH 3 had the most effect on potential leachability
      of Cu, Zn, Cd, and Ni, except Fe and Mn, at low sludge application rate. Whereas,
      only the leachability of two metals was influenced by the lowest pH (pH 3) when
      sludge applied was increased. Besides pH of leachant, it appeared that
      leachability of elements from the soil column depended on rate of sludge applied,
      the particular metal, and metal form or fraction. The soil studied had organic
      matter, CEC, pH, clay content, etc., that resulted in high buffering capacity,
      which favors metal retention. Less than 0.5 and 1.8% of the added Cu and Zn
      applied at the 150 and 300 kgN/ha application rates, respectively, were detected
      in the leachate. Approximately 100% of the added Cu and Zn in the sludge remained
      in the surface 10 cm at each sludge application rate. Sequential extraction of
      sludge-amended soil following leaching (at the high sludge application rate)
      revealed that most of the Cu remained in the surface sludge-amended soil layer (0
      2 cm depth) in the form of organic and residual Cu fractions that are not easily
      mobilized. An exchangeable fraction of Zn increased, approximately representing
      60% total Zn applied in sludge-soil layer as compared with its native soil Zn
      fractions. These results demonstrate that Zn availability in the soil would
      increase as a result of sludge application. However, the total Zn in the leachate
      is safe for agricultural use, because it represents an amount of less than 2% of
      total Zn applied.

PMID- 12049117
TI  - Release potential of phosphorus in Florida sandy soils in relation to phosphorus
      fractions and adsorption capacity.
AB  - Information on P release potential in relation to labile P and P fractions in
      sandy soils is limited. In this study, P release potential was determined by
      leaching, and labile P, soil P fractionation, and P adsorption capacity were
      measured in the laboratory using 96 Florida sandy soil samples to evaluate the
      relationship between P release in water and soil P status. The sandy soils had a
      very low P adsorption capacity. The adsorption maximum, as calculated from the
      Langmuir equation, averaged 40.4 mg P kg(-1). More than 10% of the soil P was
      water soluble, indicating a high risk of P leaching from soil to water.
      Successive leaching using deionized water released, on average, 7.7% of total P
      (144.5 mg kg(-1)) in different soils, whereas labile P recovered by successive
      water extraction accounted for 39.2% of the total P. Variation in release
      potential among the different soils could be explained more by the difference in
      amounts of extractable P than the adsorption capacity. Total amounts of P
      released by successive leaching were significantly correlated with all labile P
      indices measured by different methods and all soil P fractions except for
      residual P. The correlation coefficients (r) were 0.97** for water-soluble P,
      0.96** for 0.01 M CaCl2-P, 0.94** for Olsen P, 0.86** for Mehlich 1-P, 0.77***
      for Mehlich 3-P, and 0.64*** for Bray 1-P. There were no obvious turning points
      in the relationships between Olsen-P, water-soluble P, or CaCl2-P and the amounts
      of P released from the sandy soils. The release of P from the sandy soils
      appeared to be controlled by a precipitation-dissolution reaction rather than a P
      sorption-desorption process. Furthermore, the sequential extraction of soils
      using deionized water indicated that P released was not limited to the labile P
      (H2O-P, NaHCO3-IP) and potentially labile P (NaOH-P) pools, but also from the HCl
      P, indicating that all of P fractions except for residual P in the sandy soils
      can contribute to P release.

PMID- 12049118
TI  - Stability of Ca2+-, Cd2+-, and Cu2+-illite complexes.
AB  - In this study, using ion selective electrode techniques, we investigated the
      influence of pH on metal-ion, Ca2+, Cd2+, and Cu2+, adsorption by Fithian illite.
      The results showed that Fithian illite exhibited at least two types of metal-ion
      adsorption sites, high and low strength with the strength of metal-ion-illite
      surface complexes following the order of Cu2+ > Cd2+ > Ca2+ (strongest to weakest
      acids) at any of the pH values tested. The ability of metal-ions to form
      complexes with illite surfaces was affected by type of metal-ions and pH,
      especially for low metal-ion affinity sites. These sites formed stronger metal
      ion complexes at high pH than at low pH, which implicated clay edge sites and
      indicated that H+ competed with metal-ions for available complexation sites. The
      data also showed that illite functional groups forming the strongest metal-ion
      complex did not appear to be pH-sensitive, which implicated wedge siloxane
      cavities or extremely low pKa clay-edge OH functional groups, but the total
      number of such sites were very small. The magnitude of the metal-ion-illite
      stability constants, as metal-ion solution concentration approached zero, on a
      log-scale, varied from 3.52 to 4.21 for Ca2+, 4.38 to 5.18 for Cd2+, and from
      5.23 to 5.83 for Cu2+. These constants were approximately an order of magnitude
      smaller than those representing illite with sorbed humic fractions. The above
      results along with the results from our previous studies imply that metal-ion
      mobility and bioavailability would be affected by soil mineral surface
      properties, which would be significantly influenced by sorption of humic
      substances.

PMID- 12049119
TI  - Emissions of submicron particles from a direct injection diesel engine by using
      biodiesel.
AB  - Small airborne particles less than 1 microm in diameter have a high probability
      to deposit deeply in the respiratory tract and cause respiratory diseases such as
      lung cancer. In this study, emission characteristics of submicron particles from
      a direct injection diesel engine using biodiesel (provided by the American
      Soybean Association) and petroleum-diesel fuels were measured under different
      operation conditions. The results show that the emitted particle sizes for both
      fuels are about the same. But when fueled with biodiesel, the diesel engine can
      substantially reduce 24-42% emission of the total number concentration, and 40
      49% of the total mass concentration of submicron particles, which indicates that
      the emission of submicron particles can be effectively approved.

PMID- 12049120
TI  - Naphthalene removal from aqueous systems by Sagittarius sp..
AB  - Naphthalene is a polyaromatic hydrocarbon (PAH) present in many sediment-water
      systems. The uptake of naphthalene by an aquatic plant, arrowhead (Sagittaria
      sp.), was studied in a series of batch systems and continuous flow systems. Batch
      experiments were conducted in a fed-batch mode, and naphthalene was administered
      in consecutive spike doses. Results from batch experiments indicated that the
      rate of naphthalene removal by arrowhead in the presence of light was 0.114+/
      0.061 h(-1), at a 90% confidence interval. Naphthalene removal by arrowhead
      occurred even in the absence of light, although this rate was about 25% of that
      in the presence of light. Results indicated that repeated exposures to
      naphthalene for a single arrowhead plant may decrease its capacity for
      naphthalene uptake, particularly after the first exposure. Naphthalene tended to
      deposit out in CSTRs where no arrowhead was present, indicating that while the
      naphthalene may not have been present in the water column, it was not removed
      from the system. Results from CSTR experiments indicated that under well-mixed
      quasi-steady state conditions, naphthalene removal by arrowhead in the presence
      of light was about 40%. Photolytic degradation of naphthalene in the absence of
      arrowhead was about 15%, when additional mixing was provided to simulate
      scouring.

PMID- 12049121
TI  - Enhanced nutrient removals using conventional anoxic biomechanic aerobic system
      for on-site wastewater treatment.
AB  - A bench-scale absorbent biofilter system combined with a conventional anoxic
      process was investigated in regard to its feasibility for removing organic as
      well as nutrient materials from small community wastewater in Korea. A
      polyurethane biofilter medium with high porosity and a large surface area were
      used for the aerobic system. Part of treated wastewater was recirculated into the
      anoxic process to promote removal rate of nutrients. At three different ratios of
      recirculation, the BOD and SS of treated wastewater satisfied standard
      regulations for a small wastewater treatment facility (10 mg/l) during the
      overall experimental period. The system reduced the concentration of BOD from
      approximately 130 mg/l to 6.1 (removal rate of 95.2%) and 1.7 mg/l (removal rate
      of 98.7%). These results correspond to recirculation ratios of 1 and 2,
      respectively. A further increase of the recirculation ratio did not significantly
      improve the removal rate or further reduce effluent BOD concentration. Nutrients
      such as nitrogen and phosphorus also were removed effectively, with maximum
      removal rates of 65.3 and 84.1% for nitrogen and phosphorus, respectively. The
      recirculation ratio for optimum nitrogen removal was 2, while the removal of
      phosphorus continued to increase across the entire range of recirculation ratios
      tested. With a recirculation ratio of 2, the total phosphorous removal rate
      increased dramatically as initial ammonium concentration increased, while
      nitrogen removal was not affected in this manner. During the experimental period
      of 2 years, the system was quite stable, requiring the minimum amount of
      maintenance and a relatively low cost compared to other utility expenses. Based
      on the experimental data, the proposed anoxic-biofilter aerobic recirculation
      system might be used as a new alternative technology for wastewater treatment in
      small communities in Korea.

PMID- 12049122
TI  - Removal of Cu, Cr, Ni, Zn, and Cd from electroplating wastes and synthetic
      solutions by vermicompost of cattle manure.
AB  - This study was undertaken to evaluate the retention of Cu, Cr, Ni, Zn, and Cd
      under laboratory conditions from synthetic solution and electroplating wastes by
      vermicompost. A glass column was loaded with vermicompost, and metal solutions
      were passed through it. Metal concentrations were then measured in the eluate in
      order to evaluate the amounts retained by the vermicompost. Measurements of pH,
      metal concentrations, moistness, organic matter and ash contents, and infrared
      and XRD spectroscopy were used for vermicompost characterisation. Vermicompost
      residues obtained from this process were used for plant nutrition in eroded soil
      collected from a talus near a highway. Metal retention (in g of metal/kg of
      vermicompost) from effluents ranged from 2 for Cr and Zn to 4 in the case of Ni.
      In synthetic solutions, the values for metal retention were 4 for Cd and Zn, 6
      for Cu and Ni, and 9 for Cr. The results also showed that metal concentrations in
      the purified effluents were below the maximum values established for waste
      discharges into rivers by the Brazilian Environmental Standards. The relatively
      high available Cd concentration of the vermicompost residue resulted in plant
      damage. This effect was attributed to the presence of Cd in the synthetic
      solution passed through the vermicompost. The data obtained do not give a
      complete picture of using vermicompost in cultivated lands, but such values as
      are determined do show that it can be suitable to remove heavy metals from
      industrial effluents.

PMID- 12049123
TI  - Studies on the use of neem products for removal of ammonia from brackishwater.
AB  - Laboratory experiments were carried out to investigate the ammonia removal from
      brackishwater (Salinity 16 +/- 1 ppt) using natural plant products such as seed
      powder and seed oil from neem (Azadirachta indica) and commercially available
      neem products-neemazal and neemgold. The experimental results showed that ammonia
      removal was effective with 90 mg/l of neem oil, whereas, neem seed powder at 90
      mg/l registered an increase in ammonia levels throughout the course of the
      experiment. Neem oil, neemazal, and neemgold at 90 mg/l were effective in
      decreasing the total ammonia nitrogen (TAN) level of 0.40-0.45 mg/l in 96 h. The
      effect of initial ammonia concentrations on the ammonia removal using neem oil
      revealed that percentage ammonia removal decreased with an increase in initial
      ammonia concentration.

PMID- 12049124
TI  - Inhibitory effect of sorbitol on acetaminophen adsorption by activated carbon.
AB  - The effective use of activated carbon as oral adsorbent in the primary treatment
      of acute acetaminophen poisoning was studied. The adsorption characteristics of
      acetaminophen onto activated carbons in presence of sorbitol were investigated in
      vitro. Both the equilibrium amount adsorbed and the removal rate of acetaminophen
      onto activated carbon were decreased with the increase of sorbitol concentration
      in solutions. The sorbitol concentration independency of the inhibition to the
      acetaminophen adsorption was recognized. It was concluded that the addition of
      sorbitol to the suspension of activated carbon inhibited the acetaminophen
      adsorption by activated carbon.

PMID- 12049125
TI  - In situ experimental evidence of phosphorus limitation on algal growth in a lake
      ecosystem.
AB  - This paper presents the results of in situ Nutrient Stimulation Experiments
      (NSEs) demonstrating that phosphorus was the primary nutrient controlling algal
      growth in the Taechung Reservoir, Korea. Algal response in most treatments with
      only nitrogen added was less than or the same as in the controls, whereas the
      growth in treatments enriched with phosphorus increased by as much as fivefold.
      Phosphorus limitation was consistent over the experimental period when bioassay
      experiments were conducted, but the magnitude of growth response to phosphorus
      enrichments varied with the season. Algal yield in P-treatments was maximum when
      thermal stratification was strong and total dissolved phosphorus (TDP) was near
      the level of depletion. Regression analyses of NSEs showed that in situ algal
      response in P treatments, measured as log-transformed CHLf:CHLi ratios, declined
      (R2 = 0.995, p < 0.001) with ambient concentrations of log-transformed TDP. Also,
      algal response in the P treatments showed a first-order linear fit (R2 = 0.961, p
      < 0.001) with log-transformed DIN (dissolved inorganic nitrogen):TDP ratios.
      These outcomes indicate that the magnitude of in situ algal response increased
      with lower levels of P and higher dissolved N:P ratios in the ambient lake water.
      Our experimental approach employing NSEs suggests that abatement of phosphorus
      from the watershed seems to be an efficient management strategy to control the
      eutrophication of this system.

PMID- 12049126
TI  - Adsorption of anionic surfactant by a low-cost adsorbent.
AB  - This study was undertaken to evaluate the efficiency of rubber granule, a low
      cost adsorbent for the removal of sodium dodecyl sulfate (SDS) that is a
      representative member of anionic surfactant (AS). In the batch experiments
      conducted at an initial concentration range of 2-6 mg/l, it was found that the
      rubber granules selected could remove SDS from water up to 90%. Kinetic profiles
      were developed for various conditions. Effects of adsorbent size, initial
      adsorbate concentration and adsorbent dose, pH, Ca2+ ion concentration, Fe2+ ion
      concentration, Cl- ion concentration, and ionic strength on the adsorption of SDS
      on rubber granules were studied. The adsorption isotherm studies were also
      conducted.

PMID- 12049128
TI  - Passive nutrient addition for the biodegradation of ethylene glycol in storm
      water.
AB  - This laboratory proof-of-concept research examined the feasibility of adding
      solid, slow-release macronutrients to a biofilm reactor system to achieve the
      effective biodegradation of a predominately organic polluted storm water. The
      target scenario was treating ethylene glycol in storm water, representing the
      runoff of airport deicing and anti-icing fluids. However, the results can also be
      generalized for any water polluted with a predominately carbonaceous material.
      The use of a solid, slow-release nutrient source, compared to amending with a
      soluble solution in proportion to influent flow, would be ideal for storm water
      applications and other specialized wastewater flows when maintenance requirements
      and operational support must be minimized. Several commercially available
      fertilizers were preliminarily examined to determine which had the best potential
      to provide the required amount of nutrients. A time-released, polymer-coated
      granular fertilizer was ultimately selected. Based on laboratory studies, it was
      found that this fertilizer could provide a controllable source of macronutrients
      that enabled treatment to a similar degree as if the macronutrients had been
      dissolved in the influent. The only major operational problem was reduced
      nutrient delivery from the fertilizer after it became coated with a thick
      biofilm. However, the inherent intermittent nature of storm water production
      resulting in wet/dry cycles may minimize the development of a thick biofilm.

PMID- 12049127
TI  - The influence of the root zone temperatures on the phytoextraction of boron and
      aluminium with potato plants growing in the field.
AB  - The effect of different root zone temperatures on the concentration and content
      of B and Al in potato plants was examined using four different treatments of
      plastic mulches: T1: transparent polyethylene; T2: white polyethylene; T3:
      coextruded black and white polyethylene; T4: black polyethylene. An open-air
      treatment (T0) was used as control. The results showed significantly positive
      effects of the plastic covers on the root-zone temperatures: T0 = 16 degrees C,
      T1 = 20 degrees C, T2 = 23 degrees C, T3 = 27 degrees C, T4 = 30 degrees C. These
      different soil temperature conditions significantly altered the B concentrations,
      with T3 promoting the greatest concentrations and phytoaccumulation. The root
      zone temperature treatments induced higher concentrations and accumulation of Al
      in the T2 and T3 treatments in the roots, tubers, and leaves. The T2 and T3 lead
      to high levels of pectins in the roots, tubers, and leaves. This appears to
      reflect a possible mechanism of tolerance to the high Al and B concentrations in
      the analysed organs.

PMID- 12049129
TI  - The influence of a temporary magnetic field on chicken hatching.
AB  - The influence of magnetic field with the intensity of 0.07T on the hatching of
      the Hampshire breed chicken was investigated. The hatchability of the eggs that
      were influenced by magnetic field during the storage of the egg set (20-40 min)
      was increased in comparison with eggs that were not influenced by magnetic field
      (p < 0.05). In the eggs influenced by magnetic field during their incubation, the
      hatchability in experimental groups E1 and E2 decreased to 70.08 +/- 1.93% and
      70.75 +/- 2.13%, respectively. The difference were significant (p < 0.001) in
      comparison with the control groups C1 and C2. The negative influence of magnetic
      field was manifested by lower weight of the hatched chickens in the experimental
      groups E1 (35.07 +/- 0.95 g) and E2 (35.94 +/- 0.97 g). The results were relevant
      (p < 0.05) in comparison with the control groups with the average weight of
      hatched chickens 41.83 +/- 1.15 g (C1) and 44.27 +/- 0.73 g (C2).

PMID- 12049130
TI  - Practising alone together and the new pressures on accountability.

PMID- 12049131
TI  - Hyperlipidaemia: a need for change.

PMID- 12049132
TI  - Accessibility of intensive care facilities in Ireland to critically ill patients.

PMID- 12049134
TI  - The physical activity of children: a study of 1,602 Irish schoolchildren aged 11
      12 years.
AB  - The adoption of a physically active lifestyle is widely believed to be a
      component of preventive medicine best initiated in childhood. Information on the
      factors that influence activity behaviour is prerequisite to effective health
      promotion. Data were collected from a cohort of preadolescent children in 5th and
      6th classes of 62 Irish national primary school. 1,602 children were interviewed,
      810 girls and 792 boys. Gender differences in recreational activity were
      significant (p <.0001), and a significant decline was observed in girls' activity
      from 5th to 6th class (p<.0001). Evidence of social class effect on behaviour was
      not convincing. In regression analysis, primary PE (B,0.016, 95% CI 0.012 to
      0.021, p <.0001). gender (B, -.209, 95% CI -.277 to -.141, p < .0001), sports
      club membership (B,.201, 95% CI .131 to .272, p < .0001), and social integration
      status (B, .039, 95% CI .024 to .055, p < .0001) were identified as significant
      independent predictors of recreational activity. Parental support and physical
      self-perception were weak predictors. Findings suggest that the primary school
      plays an important role in the socialisation of children into active lifestyles.

PMID- 12049133
TI  - The road to a greener hospital.
AB  - The healthcare industry has as its major objective, the improvement of the health
      of the population. With this in mind it is a complete contradiction for hospitals
      to pollute the environment or unnecessarily consume resources. As part of the
      implementation of an environmental management system, we analysed the different
      environmental impacts the National Maternity Hospital has on the environment. In
      particular, we quantified the consumption of energy, water and wastes produced.
      RESULTS: Reduction of negative environmental impacts and cost savings can easily
      be achieved. Energy consumption can decrease by 20%, water consumption by 15%.
      Proper waste segregation requires continuous staff training and can result in
      reductions of up to 40% of healthcare risk waste. CONCLUSIOS: common sense,
      policies and procedures applied result in reductions of environmental impacts.
      Environmental management systems do not manage themselves and require dedicated
      staff to be successful. Hospital are obliged morally and legislatively to
      minimise environmental impacts by ensuring efficient use of resources.

PMID- 12049135
TI  - A case of frog breathing.
AB  - Frog breathing (glossopharyngeal breathing) is a useful technique employed to
      increase ventilation when respiratory muscles are paralysed. It is a technique
      used by many patients with chronic poliomyelitis, yet many chest physicians and
      physiotherapists are unfamiliar with this breathing maneuver. Glossopharyngeal
      breathing coordinates movements of the tongue, cheeks and pharynx to force air
      from the mouth into the lungs. We report a case of glossopharyngeal breathing,
      demonstrating a 3 fold increase in vital capacity in a subject with chronic
      poliomyelitis.

PMID- 12049136
TI  - Deliberate self poisonings in children and adolescents--a frightening scourge.
AB  - Paediatricians may be called on to see a suicidal child or adolescent in the
      emergency department as a psychiatric consultation is not always immediately
      available. The paediatrician will then play a pivotal role in the evaluation and
      disposition of the patient.(1) American reports have shown that 8% of high school
      students have made a suicidal attempt and that 2% had made an attempt that
      required medical attention.(2) Suicidal attempts account for 12% of all emergency
      department visits for the adolescent age group.(3) In the U.K. overdoses account
      for 4.7% of all general hospital admission in those aged 12-20 years. (4) In
      Republic of Ireland the most recent national vital statistics data revealed that
      over a period of one year July'97 - July '98, more than 650 children and
      adolescents were admitted to hospital with the deliberate self poisoning. The
      female to male ratio was 3:1.(7)

PMID- 12049137
TI  - The Localio approach: a technical note for a large sacral chordoma.
AB  - Whenvever possible, radical resection of retrorectal tumours should be
      performed.(1) We describe the Localio technique (abdominosacral approach) in a
      case of a large malignant sacral chordoma. We emphasise the necessity to perform
      such an approach to achieve a radical resection for these tumours which have
      little chemosensitivity and minimal radiosensitivity. We highlight clinical
      features which suggest the presence of a spinal tumour and reiterate the absolute
      importance of rectal examination.

PMID- 12049138
TI  - Per-anal extrusion of a disconnected ventriculoperitoneal catheter--an unusual
      complication.

PMID- 12049139
TI  - Illegal sales of cigarettes to children in Cork City.

PMID- 12049140
TI  - Chondrosarcoma of the nasal septum.

PMID- 12049141
TI  - Routine examination of the newborn in Ireland.

PMID- 12049142
TI  - Inflammatory bowel disease in the traveller community.

PMID- 12049143
TI  - Characterization of the proteins of pili nut (Canarium ovatum, Engl.).
AB  - The storage proteins of the pili nut (Canarium ovatum, Engl.), quantitatively
      extracted using the modified Osborne protein fractionation scheme, revealed that
      the aqueous soluble globulin was the main storage protein within the kernel
      (i.e., >> 60.3%). Further physicochemical characterization of this aqueous
      soluble globulin revealed that it existed in an 11S like form and was composed of
      two main subunits of 22,600 and 31,600 Da. These subunits were found to be
      disulfide-linked (in a 1:1 ratio) forming intermediary subunits (i.e., dimers)
      with a molecular weight of approximately 52,600 Da. The overall molecular weight
      of the 11S globulin was determined to be approximately 300,000 Da suggesting that
      the globulin possessed a dodecameric-like structure of 6 dimers for a total of 12
      subunits. Using differential scanning microcalorimetry, the denaturation
      temperature of the globulin was shown to occur at 89.3 degrees C. Overall, the
      pili nut 11S globulin was found to possess many similar physicochemical
      properties to those of other 11S oilseed globulins.

PMID- 12049144
TI  - Use of apple pomace as a source of dietary fiber in cakes.
AB  - Dried and powdered apple pomace was passed through 30, 50 and 60 mesh sieves to
      get pomace of varying particle size. Blends were prepared by mixing 5, 10 and 15
      percent pomace from each of the three particle sizes with wheat flour. The blends
      were evaluated for cake. Batter viscosity increased with increasing pomace level
      and decreasing particle size. Specific gravity and pH of the batter decreased
      with increasing pomace levels. Cake weight, shrinkage and uniformity index
      increased with increasing pomace levels, whereas, cake volume and symmetry index
      showed a reverse trend.

PMID- 12049145
TI  - Changes induced by infestation on some chemical properties of cowpea seeds.
AB  - Three cowpea varieties were used in the present study, Insect susceptible popular
      variety, 'Ife-brown' (IFB), an improved variety for insect resistance IT 81D-975
      (1975) and a local black cowpea variety with a white hilium adapted to diverse
      habitats, 'Akidi' (AKD). Cowpea seeds were infested with Callosobruchus
      maculatus. Crude protein content of infested and uninfested whole cowpea flour
      and protein concentrate was determined. Prolamin contents of flour and protein
      concentrates were evaluated. Fat content, free fatty acid and peroxide values of
      cowpea seeds were also determined. All determinations were carried out in
      infested and uninfested cowpea seeds in 3 replicates for each determination.
      Emulsion properties of cowpea seeds stored in 3 containers, plastic cans (PC) and
      polyethylene bags (white and black WPB/BPB) were monitored on a biweekly basis
      for 24 weeks. Varietal differences existed in the protein, fat and prolamin
      contents of cowpeas. Infestation reduced the contents of these nutrients in all
      cases. Free fatty acid contents and peroxide values were increased by > 100%.
      Infestation reduced the prolamin content by > 25% in all cases. Varietal
      differences also existed in emulsion capacities of cowpea flours; IFB and 975
      formed better and more stable emulsions than AKD flour. Storage in plastic cans
      led to better retention of the emulsion properties of the cowpeas.

PMID- 12049147
TI  - Agrobotanical traits and chemical composition of Cassia obtusifolia L.: a lesser
      known legume of the Western Ghats region of South India.
AB  - Four accessions of the lesser-known legume, Cassia obtusifolia L. (Sickle pod),
      collected from four different agroclimatic regions of Western Ghats, were
      evaluated for agrobotanical traits and chemical composition. Among the four
      accessions, the Keriparai accession had the highest values for plant height (cm),
      number of flowers per cluster, number of pods per cluster, pod length (cm), seeds
      per pod, seed weight (g) per pod and seed recovery percentage. Crude protein
      ranged from 18.56-22.93%, crude lipid was between 5.35-7.40%, crude fiber ranged
      from 6.83-9.45%, ash content ranged from 5.14-5.83% and carbohydrate varied from
      57.00-60.69%. Globulins constituted the bulk of the seed protein as in most
      legumes. Mineral profiles, viz., sodium, potassium, calcium, magnesium,
      phosphorus, iron, copper, zinc and manganese ranged from 42.92-84.83, 758.05
      1555.79, 559.92-791.72, 456.36-709.47, 629.13-947.79, 8.42-12.35, 0.93-2.06,
      10.60-30.04 and 2.12-4.12 mg/100 g seeds flour, respectively. Seed proteins of
      all accessions exhibited relatively high levels of non-essential and essential
      amino acids, with the exception of threonine. The in vitro protein digestibility
      of the legume ranged from 74.66 to 81.44%. Antinutritional substances such as
      total free phenolics ranged from 0.34-0.66%; tannins were between 0.47-0.60%; L
      DOPA content ranged from 0.98-1.34%; trypsin inhibitor activity varied from 11.4
      13.5 TIU/mg protein and chymotrypsin inhibitor activity ranged from 10.8-12.3
      CIU/mg protein. Phytohemagglutinating activity also was assayed. In conclusion,
      the accessions of C. obtusifolia, collected from Western Ghats, South India,
      could serve as a low-cost source of some important nutrients for humans. The
      antinutritional factors might have little nutritional significance, if the seeds
      are processed properly.

PMID- 12049146
TI  - Cassava diet--a cause for mucopolysaccharidosis?
AB  - Studies were carried out to determine the changes in glycosaminnoglycan (GAG)
      metabolism in rats fed cassava with varying cyanoglucoside levels and two levels
      of protein. Results indicated that there was an enhancement in the level of total
      and individual GAG with a corresponding reduction in the activity of enzymes
      involved in the degradation of glycosaminoglycan. These changes were significant
      for rats given a cassava diet (raw and boiled cassava) and low protein. The
      changes in total and individual GAG and the decrease in the activity of degrading
      enzymes was more for high cyanide (raw cassava) groups compared with other groups
      showing that consumption of untreated cassava is an additive factor for the
      promotion of mucopolysaccharidosis.

PMID- 12049148
TI  - Proximate composition and selected physicochemical properties of the seed, pulp
      and oil of sour sop (Annona muricata).
AB  - Proximate composition and physicochemical analyses were carried out on the seed,
      pulp and extracted oil of sour sop (Annona muricata). The results showed that the
      seed contained 8.5% moisture, 2.4% crude protein, 13.6% ash, 8.0% crude fiber,
      20.5% fat and 47.0% carbohydrate. The seed also contained 0.2% water soluble ash,
      0.79% titratable acidity and 17.0 mg calcium/100 g. The pulp was found to contain
      81% moisture, 3.43% titratable acidity and 24.5% non-reducing sugar. Selected
      physicochemical characteristics included refractive indices of 1.335 for the seed
      and 1.356 for the pulp, specific gravities of 1.250 for the seed and 1.023 for
      the pulp, pH values of 8.34 for the seed and 4.56 for the pulp, and soluble
      solids contents of 1.5 degrees Brix for the seed and 15 degrees Brix for the
      pulp. The extracted oil (20.5% yield) had a 60.43% unsaponifiable value, 23.54
      KOH/g acid value, 100.98 KOH/g saponification value, 1.1 KOH/g peroxide value,
      1.464 refractive index, 5.77 pH, 69.5 degrees Brix sosluble solids and 0.2900
      specific gravity.

PMID- 12049149
TI  - The composition of pigeon peas (Cajanus cajan (L.) Millsp.) grown in Botswana.
AB  - This study investigated the composition of pigeon peas (Cajanus cajan), grown at
      Sebele, Botswana. The raw seeds of six varieties were analyzed for dry matter,
      crude fat, protein, fiber, and ash, using Association of Official Analytical
      Chemists procedures. Major minerals, Ca, K, P, Mg, Na and trace minerals, Cu, Fe
      and Zn were also assessed. The range of nutrient contents obtained were: dry
      matter 86.6-88.0%, crude protein 19.0-21.7%, crude fat 1.2-1.3%, crude fiber 9.8
      13.0%, and ash 3.9-4.3%. Minerals ranges (mg/100 g dry matter) were: K 1845-1941,
      P 163-293, Ca 120-167, Mg 113-127, Na 11.3-12.0, Zn 7.2-8.2, Fe 2.5-4.7 and Cu
      1.6-1.8. There were no significant differences in Na among the six varieties (p >
      0.05). For the other components, varietal differences (p < 0.05) were observed.
      The values obtained for the dry matter, crude protein, fat, ash, Ca, Cu, Fe, and
      Mg were similar to those in pigeon peas grown elsewhere, while those for crude
      fiber and Zn were higher. In general, the composition of pigeon peas compared
      favorably with those of other legumes such as Bambara groundnut (Vigna
      subterranea). The levels of crude protein, crude fiber, K, Ca, P and Mg indicated
      that pigeon peas could be valuable in the diet of the people of Botswana. This
      crop would positively contribute protein in the diet and the diversification of
      agricultural produce.

PMID- 12049150
TI  - Physical, morphological and chemical characteristics, oil recovery and fatty acid
      composition of Balanites aegyptiaca Del. kernels.
AB  - Balanites aegyptiaca Del. kernels were chemically, physically and morphologically
      characterized. Crude oil (49.0%) and crude protein (32.4%) were the two major
      constituents of the kernels. Phytic acid content was relatively high compared to
      other legumes. In contrast, antitryptic activities of the kernel flours were very
      low. Sapogenin contents of the full fat, defatted and testa flours were 1.5, 2.7
      and 3.0%, respectively. The hardness of the kernel was found to be about 10.4 x
      10(5) N/m2, which was somewhat high. The morphological structure of the kernel
      using a scanning electron microscope revealed that the protein matrix was
      embedded in a lake of oil droplets. Oil recovery, as a function of pressing time,
      pressure, temperature and particle size was investigated. With increasing
      temperature up to 70 degrees C at 400 bar, for 120 min, an oil recovery of 79.4%
      was obtained. Using an expeller at 115 degrees C, about 85% of the kernel oil was
      recovered. The reduction of particle size had a negative effect on oil recovery
      under the same conditions. The fatty acid composition was not affected by the
      pressing temperature up to 115 degrees C. The total amount of the unsaturated
      fatty acids was found to be up to 74.8% (50 degrees C) and 75.1% (115 degrees C)
      of the total fatty acids content.

PMID- 12049151
TI  - Influence of storage on chemical, microbial and consumer acceptability of a milk
      like product made from melon seeds.
AB  - The storage stability of melon milk at room (30 +/- 2 degrees C) and
      refrigeration (10 +/- 2 degrees C) temperatures was determined by analyzing
      changes in the chemical, microbial and sensory properties of the milk stored for
      7 days. The results showed that at both storage temperatures, soluble solids and
      pH of the milk decreased while titratable acidity increased with storage. The
      standard plate counts increased appreciably while coliforms were absent in the
      milk with storage at both storage temperatures. The overall acceptability score
      of the melon milk dropped during storage, the drop being faster at 30 +/- 2
      degrees C than at 10 +/- 2 degrees C. The milk samples stored at 30 +/- 2 degrees
      C and 10 +/- 2 degrees C were acceptable only within one and three days,
      respectively; thereafter, they were unacceptable.

PMID- 12049152
TI  - Impact of tofu or tofu + orange juice on hematological indices of lacto-ovo
      vegetarian females.
AB  - The purpose of this study was to investigate iron status of premenopausal
      vegetarian women consuming tofu or tofu plus orange juice. Following a three day
      pre-period, 14 lacto-ovo vegetarians were randomly divided into two experimental
      periods of 30 days each. For the first 30 days, one half of the subjects (n = 7)
      received 6 oz (173 grams) of tofu/day (T) while the other half of the subjects (n
      = 7) received 6 oz of tofu/day along with 303 mg of vitamin C/d (TO). After 30
      days, there was a crossover of the diets. Iron status was assessed by measuring
      serum ferritin and hemoglobin concentrations on the first day of the study and at
      the end of each experimental period. The Mann Whitney-U test was significant
      during the first (W = 17.5; Z = -2.095; p = 0.0361) and over the second (W =
      40.0; Z = -2.611; p = 0.009) experimental periods which indicated the change in
      hemoglobin levels for the T and TO groups were different. Mean ranks showed a
      greater increase in hemoglobin levels for the TO group. There was no significant
      difference in the change in serum ferritin levels between the T and TO groups
      over the first and second experimental periods. In conclusion, bioavailability of
      iron from tofu is enhanced by supplementation with ascorbic acid.

PMID- 12049153
TI  - Theoretical and practical aspects of fast gas chromatography and method
      translation.
AB  - Interest in the development and implementation of fast gas chromatography (GC)
      methods continues to increase. Fast GC method development and validation can be
      simplified and more successful if a few key theoretical and practical concepts
      are kept in mind. Key concepts such as speed-optimized flow rate, optimal
      temperature-program rate, sample capacity, "cut the column", and principles of
      method translation are discussed.

PMID- 12049154
TI  - High-throughput capillary gas chromatography for the determination of
      polychlorinated biphenyls and fatty acid methyl esters in food samples.
AB  - High-throughput capillary gas chromatography (CGC) methods, developed during the
      Belgian 1999 "dioxin" food crisis, for the determination of the contaminating
      polychlorinated biphenyls (PCBs) and the fatty acid composition of the lipids are
      described. For PCB analysis, the fat obtained by ultrasonic extraction is
      fractionated by matrix solid-phase dispersion, and the PCBs are analyzed by CGC
      electron capture detection on a 10-mL x 100-microm-i.d. HP-5MS column. Analytical
      conditions for the high-speed column are deduced from analyses on conventional
      CGC columns using the method translation software. The concept of retention time
      locking is implemented to facilitate the elucidation of the PCB markers. The
      fatty acid methyl esters (FAMEs) are prepared by the sodium methylate procedure
      on part of the ultrasonic extract followed by analysis on 10-mL x 100-microm-i.d.
      HP-WAX or BPX-70 capillary columns. By optimizing both the sample preparation and
      CGC analysis, the throughput is more than fifty PCB and FAME samples per day with
      the same robustness as conventional methods.

PMID- 12049155
TI  - Fast gas chromatography-time-of-flight mass spectrometry of polychlorinated
      biphenyls and other environmental contaminants.
AB  - Practical applications of fast gas chromatography (GC) with time-of-flight mass
      spectrometry (TOFMS) are presented. A narrow-bore column (0.10-mm i.d.) is used
      to analyze over 100 specific polychlorinated biphenyl congeners in an Aroclor mix
      and a sediment sample in 10.5 min. Sample preparation is minimized for the
      sediment to more closely match the speed advantage gained by using fast GC-TOFMS.
      The possibility of using a 0.53-mm-i.d. column operated under vacuum-outlet
      conditions for fast GC-TOFMS is established for Aroclors and a suite of
      environmental contaminants. Fast acquisition rates and automated peak-find and
      spectral deconvolution capabilities are demonstrated for TOFMS.

PMID- 12049156
TI  - Determination of the boiling-point distribution by simulated distillation from n
      pentane through n-tetratetracontane in 70 to 80 seconds.
AB  - This work presents the carrying out of boiling-point distributions by simulated
      distillation with direct-column heating rather than oven-column heating. Column
      heating rates of 300 degrees C/min are obtained yielding retention times of 73 s
      for n-tetratetracontane. The calibration curves of the retention time versus the
      boiling point, in the range of n-pentane to n-tetratetracontane, are identical to
      those obtained by slower oven-heating rates. The boiling-point distribution of
      the reference gas oil is compared with that obtained with column oven heating at
      rates of 15 to 40 degrees C/min. The results show boiling-point distribution
      values nearly the same (1-2 degrees F) as those obtained with oven column heating
      from the initial boiling point to 80% distilled off. Slightly higher differences
      are obtained (3-4 degrees F) for the 80% distillation to final boiling-point
      interval. Nonetheless, allowed consensus differences are never exceeded.
      Precision of the boiling-point distributions (expressed as standard deviations)
      are 0.1-0.3% for the data obtained in the direct column-heating mode.

PMID- 12049157
TI  - A review of basic concepts in comprehensive two-dimensional gas chromatography.
AB  - The technique of comprehensive two-dimensional gas chromatography (GCxGC) is
      reviewed. A description of technical aspects of the method illustrates how the
      GCxGC result is achieved through the use of dual-coupled columns and the
      modulation of capillary chromatographic peaks. This review presents an expanded
      section dealing with the relationship between the modulation phase and frequency
      and the resulting peak pulse profiles. Experimental results that support the
      appreciation and understanding of the effects that pulsing has on a
      chromatographic peak are provided. The main goals of GCxGC analysis are discussed
      with respect to analytical sensitivity and peak capacity arising from zone
      compression effects and fast analysis on the second column. A typical application
      of GCxGC is presented, along with a consideration of implementation of the GCxGC
      method.

PMID- 12049158
TI  - Preparative high-performance liquid chromatography-mass spectrometry for the high
      throughput purification of combinatorial libraries.
AB  - Accurate results for the testing of combinatorial libraries necessitates high
      purity of the library members. Therefore, combinatorial libraries derived from a
      combinatorial solution or solid-phase synthesis often require the purification of
      compounds that do not achieve a certain purity threshold. This study describes
      that preparative high-performance liquid chromatography (HPLC)-mass spectrometry
      (MS) is the method of choice for the purification of large arrays of diverse
      compounds. The adoption of this technology to the workflow of a solution phase
      combinatorial chemistry laboratory producing more than 20,000 compounds per year
      is described. Furthermore, the setup and logistics are discussed as well as the
      purity achievable for large libraries. Efficiency, speed, quality, and
      universality of preparative HPLC-MS are presented in detail for a library of 140
      compounds, including data logistics and downstream processes as well.

PMID- 12049159
TI  - Plain and ion-pair thin-layer chromatography of synthetic dyes on an admixture of
      silica gel G and barium sulfate in an aqueous ethanol system.
AB  - An easy, inexpensive, and accurate method for the analysis of synthetic dyes by
      means of ion-pair thin-layer chromatography (IPTLC) on mixed sorbent phases
      containing silica gel G and barium sulfate in an aqueous ethanol system is
      studied. The effect of the composition of the sorbent phases has a major effect
      on the hundred-fold relative migration rate, as also does the effect of the ion
      pairing reagent as the impregnant. Compact and sharp spot application yields very
      good binary and ternary separations and enables their clear identification. IPTLC
      has better separations on mixed sorbent phases, which are not possible on plain
      mixed phases in thin-layer chromatography. The method can be applied for the
      trace analysis of synthetic dyes in various natural and synthetic samples.

PMID- 12049160
TI  - Gas chromatography problem solving and troubleshooting.

PMID- 12049161
TI  - Liquid chromatography problem solving and troubleshooting.

PMID- 12049163
TI  - The role of personality in task and relationship conflict.
AB  - Two studies explored the extent to which dispositions influence the attributions
      individuals make about the type of conflict they experience. Traits from the Five
      Factor Model of personality (FFM) were linked to the tendency to experience task
      and relationship-oriented conflict. Results provide some support for the idea
      that individuals have stable tendencies in the attributions they make about their
      conflict experiences across time, partners, and situations. Agreeableness and
      openness were related to reports of relationship conflict at the individual
      level. However, the strongest effects of personality on conflict attributions
      were found in the analysis of dyads. This analysis revealed that partner levels
      of extraversion and conscientiousness were associated with individuals'
      tendencies to report relationship conflict. Moreover, mean levels of extraversion
      and conscientiousness in a pair were associated with reports of relationship
      conflict. Differences between partners in extraversion were associated with more
      frequent conflict and a greater likelihood of reporting task-related conflict.
      Implications of these findings with respect to the role of personality in
      interpersonal relationships are discussed. Finally, these studies provide
      confirmatory evidence that conflict attributions have a meaningful impact on
      relationship satisfaction.

PMID- 12049162
TI  - The meaning of autonomy: on and beyond the interpersonal circumplex.
AB  - Review of existing psychological literature suggests that conceptions of autonomy
      as an individual difference have taken several forms. Structural analyses of 15
      self-report autonomy scales utilizing the interpersonal circumplex (IPC) and the
      Five-Factor Model (FFM) of personality as structural referents confirmed the
      presence of diverse conceptualizations of this construct. Two hundred ninety
      undergraduate students completed 15 autonomy scales, the NEO Personality
      Inventory-Revised (NEO-PI-R), and the Interpersonal Adjective Scales (IAS).
      Factor analysis revealed three unique conceptualizations of autonomy. Each factor
      was further differentiated from the others by its unique location on the IPC and
      its distinct relationships with the domains and facets of the NEO-PI-R.
      Evaluation of these findings within the context of existing autonomy research
      leads to the conclusion that only two of the three identified factors reflect
      autonomy. Factor I, Depressogenic Vulnerability, though relatively consistent
      with its theoretical foundation, lacks the agentic quality one would expect in an
      autonomy construct. Factors II and III, presently labeled Self-governance and
      Agentic Separation, respectively, share an agentic core but differ considerably
      in their interpersonal content. Theoretical and empirical implications of these
      findings are discussed.

PMID- 12049164
TI  - Life-satisfaction is a momentary judgment and a stable personality
      characteristic: the use of chronically accessible and stable sources.
AB  - Social cognition research indicates that life-satisfaction judgments are based on
      a selected set of relevant information that is accessible at the time of the life
      satisfaction judgment. Personality research indicates that life-satisfaction
      judgments are quite stable over extended periods of time and predicted by
      personality traits. The present article integrates these two research traditions.
      We propose that people rely on the same sources to form repeated life
      satisfaction judgments over time. Some of these sources (e.g., memories of
      emotional experiences, academic performance) provide stable information that
      explains the stability in life-satisfaction judgments. Second, we propose that
      the influence of personality traits on life satisfaction is mediated by the use
      of chronically accessible sources because traits produce stability of these
      sources. Most important, the influence of extraversion and neuroticism is
      mediated by use of memories of past emotional experiences. To test this model,
      participants repeatedly judged life-satisfaction over the course of a semester.
      After each assessment, participants reported sources that they used for these
      judgments. Changes in reported sources were related to changes in life
      satisfaction judgments. A path model demonstrated that chronically accessible and
      stable sources are related to stable individual differences in life-satisfaction.
      Furthermore, the model supported the hypothesis that personality effects were
      mediated by chronically accessible and stable sources. In sum, the results are
      consistent with our theory that life-satisfaction judgments are based on
      chronically accessible sources.

PMID- 12049165
TI  - Goal construction, reconstruction and depressive symptoms in a life-span context:
      the transition from school to work.
AB  - This study focused on investigating the kinds of personal goals young adults have
      when they are faced with the transition from school to work; the extent to which
      they reconstruct these goals as a consequence of their success in dealing with
      this transition; and how their goals influence their depressive symptoms. In
      order to investigate these research questions, 250 young adults who were facing a
      transition from school to work were studied at three points of the transition
      process: while they were still at school; 8 months after their graduation; and
      1.5 years after it. At each measurement point, they were asked to complete the
      Personal Project Analysis, a revised form of Beck's Depression Inventory, and the
      Work Status Questionnaire. The results revealed that the outcomes of young
      adults' efforts to deal with the transition from school to work had consequences
      for the ways in which they reconstructed their goals: Those who were successful
      in this transition showed a decline in the number of personal goals that did not
      relate to the next stages of this particular developmental trajectory, whereas
      those who had problems turned to goals that concerned other life domains, as an
      alternative, compensatory control strategy. The results also revealed that the
      impact of personal goals on depressive symptomatology was moderated by
      individuals' life situations following the transition: Work-related goals reduced
      individuals' depressive symptoms only among those who had been able to find a
      job, whereas self-related goals decreased it in a moratorium-type of life
      situation.

PMID- 12049166
TI  - Global positive expectancies of the self and adolescents' substance use
      avoidance: testing a social influence mediational model.
AB  - Grounded in theories of global positive expectancies and social influences of
      behavior, this investigation posited a model in which global positive
      expectancies are related to substance use as mediated by attitudes, subjective
      norms, self-efficacy, and intentions. Using a cohort sample (n = 525), structural
      equation modeling was employed to test the hypothesized predictions of future
      substance use. The findings suggest that, relative to adolescents with lower
      global positive expectancies, adolescents with higher global positive
      expectancies use substances less frequently over time because of their protective
      attitudinal and control-oriented perceptions towards that behavior. Additionally,
      results from the current investigation also extend prior findings on the factor
      structure of global positive expectancies, suggesting these expectancies can be
      viewed as a second-order factor representing optimism and two components of hope
      agency and pathways.

PMID- 12049167
TI  - Differences in MHC class I genes between strains of rainbow trout (Oncorhynchus
      mykiss).
AB  - In rainbow trout there is only one dominant classical MHC class I locus, Onmy
      UBA, for which four very different allelic lineages have been described. The
      purpose of the present study was to determine if Onmy-UBA polymorphism could be
      used for strain characterisation. This was performed by lineage-specific PCR
      investigation of 30 fish, each of the Nikko and Donaldson strains, and by
      sequence analysis of 25 of the amplified DNA fragments. Two new MHC class I
      lineages were detected in addition to the four previously described lineages,
      thus six distinct lineages were observed within the fish examined (Sal-MHCIa*A
      F). The distribution of lineages appeared to be strain-specific. For example, the
      lineage Sal-MHCIa*A was very common in the Nikko strain but could not be detected
      in the Donaldson strain. Analysis of MHC class I variation may help to elucidate
      relationships between strains and the roles of MHC alleles in disease resistance.

PMID- 12049168
TI  - Effects of rearing temperature on immune functions in sockeye salmon
      (Oncorhynchus nerka).
AB  - To determine if the defences of sockeye salmon (Oncorhynchus nerka) raised in
      captivity are affected by the rearing temperature or their life-cycle stage,
      various indices of the humoral and cellular immune functions were measured in
      fish reared at either 8 or 12 degrees C for their entire life-cycle. Measures of
      humoral immunity included the commonly used haematological parameters, as well as
      measurements of complement, and lysozyme activity. Cellular assays quantified the
      ability of macrophages from the anterior kidney to phagocytise Staphylococcus
      aureus cells, or the activities of certain bactericidal systems of those cells.
      The T-dependent antibody response to a recombinant 57 kDa protein of
      Renibacterium salmoninarum was used to quantify the specific immune response.
      Fish were sampled during the spring and fall of their second, third and fourth
      years, corresponding to a period that began just before smolting and ended at
      sexual maturation. Fish reared at 8 degrees C tended to have a greater percentage
      of phagocytic kidney macrophages during the first 2 years of sampling than the
      fish reared at 12 degrees C. During the last half of the study the complement
      activity of the fish reared at 8 degrees C was greater than that of the 12
      degrees C fish. Conversely, a greater proportion of the blood leucocytes were
      lymphocytes in fish reared at 12 degrees C compared to the fish reared at 8
      degrees C. Fish reared at 12 degrees C also produced a greater antibody response
      than those reared at 8 degrees C. Results suggested that the immune apparatus of
      sockeye salmon reared at 8 degrees C relied more heavily on the non-specific
      immune response, while the specific immune response was used to a greater extent
      when the fish were reared at 12 degrees C. Although a seasonal effect was not
      detected in any of the indices measured, varying effects were observed in some
      measurements during sexual maturation of fish in both temperature groups. At that
      time there were dramatic decreases in complement activity and lymphocyte numbers.
      This study was unique in its scope because it was the first quantitative
      assessment of salmon immune functions for an entire life-cycle.

PMID- 12049169
TI  - Ubiquitin genes in rainbow trout (Oncorhynchus mykiss).
AB  - Ubiquitin is a small protein involved in intracellular proteolysis. It is highly
      conserved throughout eukaryotic phyla and has been detected in such diverse
      species as yeast, barley, Drosophila and man. A previous study showed that
      chromatin of rainbow trout testis contains free ubiquitin with a sequence similar
      to that of other phyla. In the present study, which focused on rainbow trout but
      included eleven other species, it is shown that fish ubiquitin genetic
      organisation and expression are similar to those of other phylogenetic groups
      through the following set of observations: (a) Multiple loci were detected, (b)
      These loci encode repeats of ubiquitin, (c) Although the DNA sequences are not
      conserved, the encoded amino acid sequences are fully conserved, (d) The
      expression of ubiquitin was influenced by cell culture conditions and viral
      infection.

PMID- 12049170
TI  - Generation of superoxide anion and SOD activity in haemocytes and muscle of
      American white shrimp (Litopenaeus vannamei) as a response to beta-glucan and
      sulphated polysaccharide.
AB  - Juvenile American white shrimp (Litopenaeus vannamei) were immersed in aerated
      beta-glucan and sulphated polysaccharide solutions for 1, 3 and 6 h. Superoxide
      anion and SOD activity in haemocytes and muscle were investigated to evaluate
      whether beta-glucan and sulphated polysaccharide induce any immunostimulatory
      activity. Haemocytes and muscle showed different levels of superoxide anion
      generation and SOD activity (2.0 and 14 times that of control, respectively) when
      shrimp were immersed for 6 h in aerated sea water containing beta-glucan and
      sulphated polysaccharide. Total haemocyte count (THC) decreased within the first
      24 h after challenge with immunostimulants, but THC and total soluble haemocyte
      protein increased over normal values after 48-120 h. Single immunostimulation
      with beta-glucan and sulphated polysaccharide is capable of generating an
      increase in the respiratory burst of L. vannamei haemocytes.

PMID- 12049171
TI  - Amylase and aspartate aminotransferase in the haemolymph of the European flat
      oyster Ostrea edulis.

PMID- 12049172
TI  - Progress in high throughput SNP genotyping methods.
AB  - Most current single nucleotide polymorphism (SNP) genotyping methods are still
      too slow and expensive for routine use in large association studies with hundreds
      or more SNPs in a large number of DNA samples. However, SNP genotyping technology
      is rapidly progressing with the emergence of novel, faster and cheaper methods as
      well as improvements in the existing methods. In this review, we focus on
      technologies aimed at high throughput uses, and discuss the technical advances
      made in this field in the last few years. The rapid progress in technology, in
      combination with the discovery of millions of SNPs and the development of the
      human haplotype map, may enable whole genome association studies to be initiated
      in the near future.

PMID- 12049173
TI  - Intra-individual variation and sex differences in gene expression of cytochromes
      P450 in circulating leukocytes.
AB  - To clarify partly inconsistent results in gene expression of cytochromes P450
      (CYP) in the circulation, we undertook a systematic study over a long time period
      in 19 healthy men and women. CYP specific mRNA for 1A2, 1B1, 2E1 and 3A4 was
      studied in the leukocytes collected repeatedly on 20 occasions over a 10-week
      period. Our study revealed a varying pattern of CYP expression over time. CYP3A4
      specific mRNA exhibited the largest intra-individual variation with an average
      coefficient of variation between 40 and 250%. CYP1B1 and CYP2E1 did not vary as
      much (39-110%). CYP1A2 was sporadically detected in only ten individuals, but
      varied considerably when measurable (61-256%). The expression in CYP1B1 was
      significantly higher in women than in men (P = 0.02). We conclude that CYP gene
      expression in blood varies considerably over time. It is conceivable that the
      variation reflects a hitherto unknown influence of exogenous or endogenous
      factors such as hormones, cytokines, and other circulating factors on the
      hematogeneous cytochromes.

PMID- 12049174
TI  - Specific and overlapping functions of the nuclear hormone receptors CAR and PXR
      in xenobiotic response.
AB  - The products of the cytochrome P450 (CYP) genes play an important role in the
      detoxification of xenobiotics and environmental contaminants, and many foreign
      chemicals or xenobiotics can induce their expression. We have previously shown
      that the nuclear hormone receptor CAR (Constitutive Androstane Receptor, NR113)
      mediates the well studied induction of CYP2B10 gene expression by phenobarbital
      (PB) and 1, 4-bis-[2-(3, 5,-dichloropyridyloxy)] benzene (TCPOBOP). We have used
      the CAR knockout mouse model to explore the broader functions of this xenobiotic
      receptor. In addition to the liver, CAR is expressed in the epithelial cells of
      the villi in the small intestine, and this expression is required for CYP2B10
      induction in response to PB and TCPOBOP in those cells. In agreement with
      previous observations that CAR can bind to regulatory elements in CYP3A genes,
      CAR is also required for induction of expression of CYP3A11 in response to both
      PB and TCPOBOP in liver. In males, CAR is also required for induction of liver
      CYP2A4 expression. In wild type animals, pretreatment with the CAR inverse
      agonist androstenol blocks the response of both the CYP2B10 and CYP3A11 genes to
      PB and TCPOBOP, and decreases basal CYP3A11 expression. CAR is also required for
      the response of CYP2B10 to several additional xenobiotic inducers, including
      chlorpromazine, clotrimazole and dieldrin, but not dexamethasone, an agonist for
      both the xenobiotic receptor PXR (Pregnane X Receptor NR112) and the
      glucocorticoid receptor. Chlorpromazine induction of CYP3A11 is also absent in
      CAR-deficient animals, but the responses to clotrimazole and dieldrin are
      retained, indicating that both of these inducers can also activate PXR (Pregnane
      X Receptor NR112). We conclude that CAR has broad functions in xenobiotic
      responses. Some are specific to CAR but others, including induction of the
      important drug metabolizing enzyme CYP3A, overlap with those of PXR.

PMID- 12049176
TI  - Will pharmacogenomics guide clinical practice?

PMID- 12049175
TI  - Pharmacogenetic investigation of the TNF/TNF-receptor system in patients with
      chronic active Crohn's disease treated with infliximab.
AB  - Infliximab (anti-TNF-alpha monoclonal antibody) induces remission in 30-40% of
      Crohn's disease patients. Treatment response is a stable trait. Two cohorts from
      independent, prospective clinical trials of infliximab in Crohn's disease were
      studied. Hypotheses were generated in an exploratory cohort (n = 90) and then
      tested in a confirmatory cohort (n = 444), using a statistical design, which is
      stable against type 1 and type 2 errors. In the exploratory cohort, the mutant
      196Arg allele of TNFR-II (exon 6 polymorphism) and a novel silent polymorphism in
      exon 2 of TNFR-II were associated with lack of response to infliximab (83.3% in
      homozygote mutant 196 Arg patients vs 36.9% in heterozygotes and wild-type
      homozygotes (P = 0.036) and 85.7% in homozygote mutant exon 2 patients vs 36.1%
      (P = 0.01), respectively). None of the homozygote mutant individuals (0/6)
      achieved clinical remission, whereas the remission rate was 35.7% (30/84) in wild
      type homozygotes and heterozygotes. In the large second cohort, the observed
      genotype-phenotype associations were not replicated. Other polymorphisms (TNF
      alpha promoter -238, -308, -376, -857, -1031, TNF-R-I -609, +36 (exon 1), TNF-R
      II 1663, 1690 (3'-UTR)) were not associated with treatment response in both
      cohorts (P > 0.5). None of the polymorphisms was associated with refractory
      Crohn's disease itself when compared to healthy controls. In a two-cohort study,
      a series of polymorphisms in the TNF, the TNF-R-I and in the TNF-R-II genes could
      be thoroughly excluded as pharmacogenetic markers for a treatment response to
      infliximab and as etiologic factors for Crohn's disease, respectively. The
      discrepancy between the two cohorts observed for the TNF-R-II exon 6 and exon 2
      polymorphism may point to a weak effect on treatment response but also serves to
      illustrate the need for a sequential exploratory/confirmatory design in
      pharmacogenetic studies.

PMID- 12049177
TI  - The ADAMs: a new therapeutic avenue?

PMID- 12049178
TI  - Gene-environment interactions--the BioBank UK study.

PMID- 12049179
TI  - A regulatory protocol for pharmacogenomics services.

PMID- 12049180
TI  - Molecular aspects of pain research.

PMID- 12049181
TI  - An introduction to information retrieval: applications in genomics.
AB  - Information retrieval (IR) is the field of computer science that deals with the
      processing of documents containing free text, so that they can be rapidly
      retrieved based on keywords specified in a user's query. IR technology is the
      basis of Web-based search engines, and plays a vital role in biomedical research,
      because it is the foundation of software that supports literature search.
      Documents can be indexed by both the words they contain, as well as the concepts
      that can be matched to domain-specific thesauri; concept matching, however, poses
      several practical difficulties that make it unsuitable for use by itself. This
      article provides an introduction to IR and summarizes various applications of IR
      and related technologies to genomics.

PMID- 12049182
TI  - Benign isolated fibrohistiocytic tumor arising from the central nervous system.
      Considerations about two cases.
AB  - Benign fibrous histiocytomas (BFHs) are tumors with fibroblastic and histiocytic
      components without histological anaplasia. Intracerebral lesions are exceptional
      and to our knowledge a spinal location was not yet described. We describe 2 cases
      of BFHs of the neural axis: the first, a 22-month-old boy with Down's syndrome,
      presented with a paraparesis and the magnetic resonance (MR) of the spine
      disclosed an intradural extramedullary, thoracic mass, totally resected; the
      second, a 13-year-old boy with left partial motor seizures, in whom the MR of the
      brain showed an intracerebral, right frontal tumor, also surgically removed. Both
      patients are free of recurrence, 6 years and 15 months after surgery,
      respectively. Histological examination and immunoreactivity for vimentin and
      histiocytic markers favored the diagnosis of BFH. It is likely that these tumors
      may originate from spinal dura mater mesenchymal stem cells and from the
      intracerebral perivascular pial sheath or the brain vessel walls themselves,
      respectively. Other benign, isolated, intracranial fibrohistiocytic neoplasms,
      namely the juvenile xanthogranuloma, can harbor a clinical, morphological and
      immunohistochemical profile overlapping the one of the BFH. Intracranial germ
      cell tumors may be associated with Down's syndrome, although harboring an
      unusual, non-pineal and non-chiasmatic location. One can speculate that a
      similar, still unknown genetic mechanism responsible for this association, could
      also induce the growth of other type of tumors in patients with this syndrome.
      BFHs should be added to the differential diagnosis of intracerebral or spinal
      dural attached tumors. Furthermore, we propose to name these intracranial tumors
      "benign isolated fibrohistiocytic tumors of the CNS".

PMID- 12049183
TI  - Activated microglia do not mediate the early deposition of Abeta in carriers of
      the apolipoprotein Eepsilon4 allele.
AB  - Activated microglia are a prominent component of the senile plaques in end-stage
      Alzheimer's disease, but whether microglia contribute to the initiation of the
      lesions remains unknown. In a previous postmortem study of non-demented elderly
      cases, we found that amyloidogenesis is advanced by at least 10 years in carriers
      of the apoEepsilon4 allele. To determine whether microglia are involved in the
      initial stages of beta-amyloid pathogenesis and whether apoE genotype influences
      microglial activation, we quantified HLA-DR-immunoreactive microglia in the
      medial temporal lobe of 229 non-demented humans of various APOE genotypes who had
      died between 50 and 91 years of age. Our results show that the number of HLA-DR
      immunoreactive microglia increases with advancing age in both the gray matter and
      the white matter. In contrast to amyloid plaques and neurofibrillary tangles,
      there is no significant correlation between apoE genotype and density of
      microglia, although apoEepsilon4 homozygotes tended to have more microglia than
      did other apoE groups. In sections double-immunostained for Abeta and activated
      microglia, activated microglia were associated with dense-cored plaques but not
      with diffuse plaques, suggesting that microglial activation is a relatively late
      event in the genesis of beta-amyloid. Activation of microglia thus appears not to
      be the initial impetus for Abeta-deposition in the elderly.

PMID- 12049184
TI  - Quantitative in situ detection of high-risk human papillomavirus in cytological
      specimens by SYBR Green I fluorescent labeling.
AB  - In this study we developed an in situ protocol for quantitative detection of high
      risk human papillomavirus (HPV), based on direct in situ polymerase chain
      reaction (PCR) with SYBR Green I labeling and GeneAmp 5700 Sequence Detection
      System technology. This protocol was applied on cytological specimens of patients
      with cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC).
      We performed direct in situ quantitative PCR on cell smears, uninfected human
      skin fibroblasts, Hela and Caski cells. After in situ amplification, slides were
      counterstained with propidium iodide and analyzed under a fluorescent microscope
      in order to localize high-risk HPV and verify preservation of morphology. After
      PCR optimization, we obtained the following results. The Hela cells showed values
      ranging from 15 to 33 copies of high-risk HPV per cell, the Caski cell line from
      220 to 300 high-risk HPV copies per cell and the cell smear (both CIN and SCC)
      around 20-35 copies of high-risk HPV per cell. No high-risk HPV amplification was
      detected in uninfected human fibroblasts, healthy controls, non-amplification
      control, and non-specific primer control. A positive intranuclear high-risk HPV
      amplification was detected in cell smears from 20 patients with CIN and 10 with
      SCC. In conclusion, our in situ quantitative protocol for high-risk HPV detection
      on cell smears combines both quantitative data and in situ localization of the
      target, with preservation of morphology. For this reason it could be used as a
      rapid screening tool when both morphological and quantitative results are
      requested on the same slide.

PMID- 12049185
TI  - Serum elevations of soluble Fas (CD95/apo-I) concur in deregulating T cell
      apoptosis during active lupus disease.
AB  - Apoptosis is deregulated in active systemic lupus erythematosus and Fas is
      overexpressed by T cells, although the role of its soluble form (sFas) is
      unclear. We have explored both the biological significance and structure of sFas
      in relation to the disease activity. Serum levels of both sFas and sFas-L were
      correlated with T cell apoptosis in 26 systemic lupus eythematosus patients along
      with measurement of poly (ADP) ribose polymerase and CK18. In addition, both
      proliferative rate and change of ploidy were measured in CD3+ cells after
      treatment with sFas. Both sFas and sFas-L correlated with apoptosis in patients
      with active systemic lupus eythematosus. Incubation with sFas greatly suppressed
      proliferation of CD3+ cells from inactive patients and healthy donors, whereas
      immunoprecipitation revealed both the 48-kDa full-length Fas and the 26-kDa
      splicing variant in sera from active patients. We postulate that sFas is released
      to exert a pro-apoptogen effect. It seems possible that the apoptosis program
      itself includes the shedding/secretion of different forms of Fas to spread a
      death signal.

PMID- 12049187
TI  - Relationship between serum complement and different lipid disorders.
AB  - Inflammatory and lipid factors share an important role in atherosclerosis. Recent
      studies showed the concomitant presence and increase of complement components and
      lipids both in the atherosclerotic plaque and the circulating blood. The aim of
      this study was to examine the relationship between the complement system and
      lipid disorders. We evaluated the circulating complement terminal complex C5b-9,
      a clear sign of complement activation, in three groups of 30 patients the first
      with hypercholesterolemia, the second with hypertriglyceridemia (associated with
      low values of HDL-cholesterol), the third with low levels of HDL-cholesterol
      compared with an equivalent group of matched normolipemic subjects. We found a
      significant increase of sC5b-9 in each group of patients compared with controls.
      The mean sC5b-9 level in the hypercholesterolemic population was 366.2 +/- 141.2
      ng/ml (P<0.01), 395.4 +/- 118.2 ng/ml in the hypertrygliceridemic group (P<0.01),
      414.8 +/- 126.4 ng/ml in the low HDL-chol subjects (P<0.01), and 182.0 +/- 40.8.
      ng/ml in the control group. Regression analysis showed a significant direct
      correlation between sC5b-9 and triglycerides (r=0.64), and a significant inverse
      correlation between sC5b-9, HDL-chol (r=-0.74), and apo-A1 (r=-0.68); no
      significant relationship was found between sC5b-9 and cholesterol. We suggest
      that complement activation is associated with the various lipid disorders and is
      more important in those dyslipidemic conditions in which other factors may be
      involved. In particular, hypertriglyceridemia may be associated with endothelial
      and fibrinolytic disturbances, and the decrease of HDL may induce the failure of
      the regulatory proteins transported by the same HDL.

PMID- 12049186
TI  - A case of apolipoprotein C-II deficiency with coronary artery disease.
AB  - A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial
      infarction without pancreatitis. A coronary angiogram showed complete occlusions
      of both the right and circumflex coronary arteries. His serum lipid levels were
      as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol
      3.62 mmol/l; fasting triglycerides 1.46 mmol/A; postprandial triglycerides 6.14
      mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and
      postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level
      of plasma apolipoprotein C-II was 0.005 g/l, but his plasma levels of other
      apolipoproteins were within normal ranges. A DNA sequence analysis of the
      apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most
      gene mutations related to apolipoprotein C-II deficiency occur. We report this
      patient's very rare heterozygous apolipoprotein C-II deficiency with coronary
      artery disease. Although this patient had some risk factors for coronary artery
      disease, coronary atherosclerosis in this patient might have occurred as a result
      of lipoprotein abnormalities caused by at least one mutation in the
      apolipoprotein C-II gene.

PMID- 12049188
TI  - Correlation of P-selectin and lipoprotein(a), and other lipid parameters in
      preeclampsia.
AB  - Preeclampsia is a pregnancy specific disorder and is thought to be associated
      with generalized endothelial dysfunction. P-selectin, an adhesion molecule,
      mediates the interaction of monocytes, platelets, and endothelial cells.
      Increased P-selectin levels and altered lipid and lipoprotein metabolism were
      reported in preeclampsia and during pregnancy. In order to investigate the
      relationship between serum P-selectin and lipoprotein(a), and other lipid
      parameters, 28 preeclampsia [13 severe (group I) and 15 mild preeclampsia (group
      II), 15 healthy pregnant (group III) and 20 non-pregnant (group IV)] women were
      investigated. Serum P-selectin, lipoprotein(a), total cholesterol, triglyceride,
      and high density lipoprotein cholesterol were measured and low-density
      lipoprotein cholesterol was derived. Serum P-selectin concentrations were
      consistently and significantly higher in the severe preeclampsia group than in
      the mild preeclampsia, healthy pregnancy, and non-pregnant control groups
      (P<0.0001, for all). The mild preeclampsia group also had increased serum P
      selectin concentrations compared with the healthy pregnancy group and non
      pregnant controls (P<0.05 and P<0.0001, respectively). Serum P-selectin and
      lipoprotein(a) levels revealed a significant and linear increase with the
      severity of preeclampsia. There were also significant (in groups I and II) and
      borderline (in groups III and IV) correlations between P-selectin and total
      cholesterol. The present study suggests that P-selectin may be an additional risk
      marker for preeclampsia, and may be useful in distinguishing women with mild and
      severe preeclampsia and normal pregnancy.

PMID- 12049189
TI  - Detection and quantification of the soluble form of the human erythropoietin
      receptor (sEpoR) in the growth medium of tumor cell lines and in the plasma of
      blood samples.
AB  - The erythropoietin receptor (EpoR) belongs to the cytokine superfamily and is a
      type I transmembrane protein. Like other members of this family, EpoR is also
      synthesized as a soluble form, and is subsequently secreted by the cell. To
      investigate whether soluble EpoR (sEpoR) is expressed in human tumor cell lines,
      we developed a sensitive quantitative ELISA, using an anti-human EpoR antibody
      and recombinant sEpoR as standard control. With this ELISA, sEpoR could be
      detected in the supernatant of human tumor cell lines. Analysis of blood samples
      showed that sEpoR was coprecipitated during coagulation. Therefore only plasma
      was suitable for analysis and first measurements of plasma samples were
      investigated. In conclusion, an ELISA to quantify the sEpoR was established and
      the expression of sEpoR in human tumor cell lines was demonstrated for the first
      time.

PMID- 12049190
TI  - Diagnostic performance of arginase activity in colorectal cancer.
AB  - Arginase activity was measured in serum and biopsy from healthy individuals and
      colorectal cancer patients. Arginase activity in tumor samples (87 +/- 7.7 U/g
      tissue) was significantly higher than in controls (40.7 +/- 3.3 U/g tissue).
      However, serum arginase activity did not show any significant change in both
      groups. Finally, the micromethod used to quantify arginase activity in this study
      is superior to other methods because it has increased sensitivity, requires less
      sample, and is less time-consuming. Arginase differences are significant,
      according to the t-test (P<0.05)

PMID- 12049191
TI  - A1298C methylenetetrahydrofolate reductase mutation and coronary artery disease:
      relationships with C677T polymorphism and homocysteine/folate metabolism.
AB  - 5, 10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in
      homocysteine/methionine metabolism. The most-studied C677T polymorphism in the
      MTHFR gene results in a thermolabile variant with reduced activity, and is
      associated with increased levels of total plasma homocysteine, a risk factor for
      coronary artery disease. A new mutation in the MTHFR gene (A1298C) has also been
      reported to lower enzyme activity. Whether A1298C is a risk factor for coronary
      artery disease, separately or in combination with C677T, and/or relative to total
      plasma homocysteine and folate status, is unclear to date. We evaluated this
      hypothesis in 470 angiographically characterized subjects, 302 with coronary
      artery disease, and 168 with normal coronary arteries. The frequency of the 1298C
      allele was 0.33 and that of combined heterozygosity 0.315. No difference was
      found in the frequency of the genotypes or when analyzed for combined
      heterozygosity between patients with coronary artery disease and normals.
      Independent of folate status, the 1298C allele was not associated with increased
      total plasma homocysteine. No additional effect of A1298C on total plasma
      homocysteine was observed in 148 combined heterozygotes compared with 98
      heterozygotes for the C677T alone. These findings do not support a major role for
      the A1298C mutation in homocysteine metabolism and emphasize the hypothesis that
      MTHFR genotypes may interfere with coronary artery disease risk only when an
      unbalanced nutritional status leads to raised total plasma homocysteine levels.

PMID- 12049192
TI  - tRNA(Lys3): the primer tRNA for reverse transcription in HIV-1.
AB  - During the assembly of HIV-1, tRNA(Lys) isoacceptors are selectively packaged
      into the virion, and one of these, tRNA(Lys3), is annealed to the viral RNA
      genome where it acts to prime the reverse transcriptase (RT)-catalyzed synthesis
      of viral DNA. We review herein what is known about the selective packaging and
      annealing of primer tRNA(Lys3). Current evidence suggests that a complex of two
      major precursor viral proteins, Pr55gag and Pr160(gag-pol), interact with a
      tRNA(Lys)/lysyl-tRNA synthetase (LysRS) complex during viral assembly, with
      Pr55gag interacting with both LysRS and Pr160(gag-pol), and RT sequences within
      Pr160(gag-pol) binding to tRNA(Lys). LysRS appears to target the tRNA(Lys)
      isoacceptors for incorporation into HIV-1. In the virion, the 3' terminal 18
      nucleotides of tRNA(Lys3) anneals to an 18-nucleotide sequence at the 5' terminal
      region of viral RNA termed the primer binding site (PBS). Evidence is presented
      that other regions on the tRNA(Lys3) also anneal with other regions in viral RNA
      upstream of the PBS, resulting in a destabilized tRNA(Lys3) structure. Both viral
      and tRNA(Lys3) regions need to be denatured to establish annealing, and the roles
      of both viral and cellular proteins in this process are discussed.

PMID- 12049193
TI  - The focal adhesion kinase--a regulator of cell migration and invasion.
AB  - Cell migration plays an important role in embryonic development, wound healing,
      immune responses, and in pathological phenomena such as tissue invasion and
      metastasis formation. In this review, we summarize recent reports that connect
      the focal adhesion kinase (FAK) to cell migration and invasion. FAK is a
      nonreceptor protein tyrosine kinase involved in signal transduction from integrin
      enriched focal adhesion sites that mediate cell contact with the extracellular
      matrix. Multiple protein-protein interaction sites allow FAK to associate with
      adapter and structural proteins allowing for the modulation of mitogen-activated
      protein (MAP) kinases, stress-activated protein (SAP) kinases, and small GTPase
      activity. FAK-enhanced signals have been shown to mediate the survival of
      anchorage-dependent cells and are critical for efficient cell migration in
      response to growth factor receptor and integrin stimulation. Elevated expression
      of FAK in human tumors has been correlated with increased malignancy and
      invasiveness. Because recent findings show that FAK contributes to the secretion
      of matrix-metalloproteinases, FAK may represent an important checkpoint in
      coordinating the dynamic processes of cell motility and extracellular matrix
      remodeling during tumor cell invasion.

PMID- 12049194
TI  - Nitric oxide limits parasite development in vectors and in invertebrate
      intermediate hosts.
AB  - Nitric oxide (NO) possesses antiparasitic effects on both Protozoa and Metazoa in
      vertebrate definitive and intermediate hosts. Inducible NO limits parasite
      development also in Rhodnius prolixus and Anopheles stephensi, the natural
      vectors of human trypanosomiasis and malaria respectively, and in the snail
      Biomphalaria glabrata, a natural invertebrate intermediate host of human
      schistosomiasis. Therefore, NO limits Trypanosoma, Plasmodium, and Schistosoma
      development at all stages of the parasite life cycle.

PMID- 12049195
TI  - Animals are dependent on preformed alpha-amino nitrogen as an essential nutrient.
AB  - It has traditionally been thought that animals can utilize ammonia for amino acid
      biosynthesis, and that for them some amino acids are nutritionally nonessential.
      Presumably this idea originates from the notions of Schoenheimer (G. L. Foster et
      al. [1939] J. Biol. Chem. 127, 319-327) and of Rose (W. C. Rose et al. [1948] J.
      Biol. Chem. 176, 753-762), which we question for the following reasons. First,
      Schoenheimer's experiments only showed the incorporation of ammonia into amino
      acids. This may occur simply as an exchange between ammonia and the alpha-amino
      group of endogenous amino acids and reflects the enzymatic properties of
      glutamate dehydrogenase, which is a reversible enzyme. Second, Rose's nutritional
      experiments were concerned with whether carbon skeletons of particular amino
      acids can (nonessential) or cannot (essential) be synthesized from common
      intermediates of carbohydrate metabolism. We propose that mammals, living as they
      do at the top of the food web, are absolutely dependent directly or indirectly on
      higher plants and microorganisms for preformed alpha-amino nitrogen per se and
      that the first joining of C- and N-atoms to make glutamate constitutes a basic
      anabolic system in nature after the fixation of CO2 and N2.

PMID- 12049196
TI  - Genomic structure and promoter analysis of the bovine leptin gene.
AB  - The product of the leptin gene is a 16-kDa protein secreted by adipose tissue and
      regulates adiposity. The leptin gene could be a potential candidate gene
      controlling some proportion of adipose and lean accretion in cattle, and thus,
      may be referred to as one of genetic factor controlling meat quality determinants
      such as marbling. We have isolated the bovine leptin gene including its promoter
      region. We have determined the exon-intron organization of the bovine leptin
      gene, which consisted of three exons and two introns and spanned about 18.9 kb,
      equivalent to that of human or mouse gene. A approximately 3-kb 5'-flanking
      region upstream from the putative transcription start site of the gene contained
      consensus Sp1 and CCAAT/enhancer-binding protein (C/EBP) motifs, and transient
      transfection assay with secreted alkaline phosphatase reporter confirmed the
      promoter activity in 3T3-L1 cells that possessed expression of the cotransfected
      C/EBP alpha expression plasmid. Cotransfection with C/EBP alpha caused 24-fold
      activation in leptin reporter expression, as compared to cotransfection with
      control plasmid, consistent with existence of the putative C/EBP alpha binding
      site in the proximal 5'-flanking region of the bovine leptin gene.

PMID- 12049197
TI  - How I became a biochemist.

PMID- 12049198
TI  - Oxalate, germins, and higher-plant pathogens.
AB  - Earlier surveys (1, B. G. Lane. [1991] FASEB J. 5, 2983-2901; 2, B. G. Lane.
      [1994] FASEB J. 8, 294-301) helped to uproot entrenched views of plant oxalate as
      a static substance. It is now recognized that oxalate oxidases (OXOs) found in
      the "true cereals" (barley, maize, oat, rice, rye, wheat), the so-called germin
      OXOs (G-OXOs), or simply germins, are involved in cereal defence responses to
      invasion by fungal pathogens and that they show promise of being valuable agents
      of plant defence in dicotyledons, where they are not found naturally. G-OXOs have
      very peculiar properties: (a) their water-soluble oligomeric structures and
      enzymic activity are stable during SDS-PAGE and nitrocellulose blotting, (b)
      their undenatured water-soluble forms are refractory to the action of broad
      specificity proteases, (c) their water-insoluble forms occur abundantly
      (approximately 50%) in the extracellular matrix (cell walls) of wheat, and
      probably in varying amounts in the cell walls of other true cereals. Transfer of
      the wheat G-OXO coding element to dicotyledons has been found, in all cases so
      far examined, to result in improved resistance to fungal pathogens. The possible
      nature of the improved resistance is discussed in relation to (a) generation of
      microcidal concentrations of hydrogen peroxide when the G-OXOs act on oxalate,
      (b) elicitation of hypersensitive cell death at lower concentrations of hydrogen
      peroxide, (c) formation of effective barriers against predator penetration by the
      hydrogen-peroxide-mediated lignification of cell walls, and (d) destruction of
      oxalate, which is an inhibitor of the hypersensitive response, a strategy of
      particular importance in the case of ubiquitous predator organisms such as
      Sclerotinia sclerotiorum, which secrete high concentrations of oxalate as a
      toxin.

PMID- 12049199
TI  - Structure and function of collagen-derived endostatin inhibitors of angiogenesis.
AB  - Endostatins are inhibitors of endothelial cell migration and angiogenesis and
      have been shown to reduce tumor growth in animal models. They are derived from
      the nontriplehelical C-terminal NC1 domains of collagens XV and XVIII, which are
      released proteolytically in trimeric form and further converted to monomeric
      endostatins of about 20 kDa. Both endostatin isoforms share a compact globular
      fold, but differ in certain binding properties for proteins and cells, as well as
      in tissue distribution. Differences in activity were found between NC1 domains
      and endostatins and are related to the oligomerization state. Endostatin effects
      are not restricted to endothelial cells, but also control renal epithelial cells
      and neuronal guidance in C. elegans. Cellular receptors are still insufficiently
      characterized and include for endostatin-XVIII heparan sulfate proteoglycans.
      Receptor engagement elicits various downstream effects including tyrosine kinase
      and gene activation. Much remains to be learned, however, about details of the
      signal transduction cascades and how they interfere with pro-angiogenic factors
      under physiological conditions and during therapeutic treatment.

PMID- 12049200
TI  - Structural basis of perturbed pKa values of catalytic groups in enzyme active
      sites.
AB  - In protein and RNA macromolecules, only a limited number of different side-chain
      chemical groups are available to function as catalysts. The myriad of enzyme
      catalyzed reactions results from the ability of most of these groups to function
      either as nucleophilic, electrophilic, or general acid-base catalysts, and the
      key to their adapted chemical function lies in their states of protonation.
      Ionization is determined by the intrinsic pKa of the group and the
      microenvironment created around the group by the protein or RNA structure, which
      perturbs its intrinsic pKa to its functional or apparent pKa. These pKa shifts
      result from interactions of the catalytic group with other fully or partially
      charged groups as well as the polarity or dielectric of the medium that surrounds
      it. The electrostatic interactions between ionizable groups found on the surface
      of macromolecules are weak and cause only slight pKa perturbations (<2 units).
      The sum of many of these weak electrostatic interactions helps contribute to the
      stability of native or folded macromolecules and their ligand complexes. However,
      the pKa values of catalytic groups that are found in the active sites of numerous
      enzymes are significantly more perturbed (>2 units) and are the subject of this
      review. The magnitudes of these pKa perturbations are analyzed with respect to
      the structural details of the active-site microenvironment and the energetics of
      the reactions that they catalyze.

PMID- 12049201
TI  - BAG-1, an anti-apoptotic tumour marker.
AB  - BAG-1 is a multifunctional and anti-apoptotic or anti-cell death protein that
      interacts with a variety of cellular proteins and affects their functions. On the
      cell surface, it binds to the cytosolic domain of the growth factor receptors and
      enhances the protection from cell death triggered by growth factor receptors. In
      the cytosol, it binds to Bcl-2 and heat shock protein, and modulates their
      functions. In the nucleus, it binds to a variety of nuclear hormone receptors and
      inhibits hormone-induced apoptosis. BAG-1 is widely overexpressed in a variety of
      tumour cell lines and cancer tissues. In addition, differential expression of BAG
      1 isoforms has been observed. Preclinical studies indicate that overexpression of
      BAG-1, especially its nuclear and cytoplasmic isoforms, may be useful as a
      prognostic and/or predictive biomarker. Pilot clinical studies have demonstrated
      that overexpression of nuclear BAG-1 may be associated with a shorter survival in
      breast and laryngeal carcinomas. Conversely, overexpression of cytoplasmic BAG-1
      may be associated with a better clinical outcome in early stage breast cancer and
      in non-small cell lung cancer. Further large-scale clinical studies are warranted
      to establish the role of BAG-1 as a novel prognostic and/or predictive biomarker
      in the clinical management of these common malignancies.

PMID- 12049202
TI  - Recent progress on immobilization of enzymes on molecular sieves for reactions in
      organic solvents.
AB  - Enzymes exhibit high selectivity and reactivity under normal conditions but are
      sensitive to denaturation or inactivation by pH and temperature extremes, organic
      solvents, and detergents. To extend the use of these biocatalysts for practical
      applications, the technology of immobilization of enzymes on suitable supports
      was developed. Recently, these immobilized biomolecules have been widely used and
      a variety of immobilization supports have been studied. The majority of these
      supports cover diverse kinds of materials such as natural or synthetic
      polyhydroxylic matrixes, porous inorganic carriers, and all kinds of functional
      polymers. Microporous molecular sieve, zeolite, has attracted extensive interest
      in research because of its distinctive physical properties and geochemistry.
      Recently, with the discovery of a new family of mesoporous molecular sieves, MCM
      41, this series of materials shows great potential for various applications.
      Molecular sieves involve such a series of materials that can discriminate between
      molecules, particularly on the basis of size. As support materials, they offer
      interesting properties, such as high surface areas, hydrophobic or hydrophilic
      behavior, and electrostatic interaction, as well as mechanical and chemical
      resistance, making them attractive for enzyme immobilization. In this article,
      different types of molecular sieves used in different immobilization methods
      including physical adsorption on zeolite, entrapment in mesoporous and
      macroporous MCM series, as well as chemically covalent binding to functionalized
      molecular sieves are reviewed. Key factors affecting the application of this
      biotechnology are discussed systematically, and immobilization mechanisms
      combined with newly developed techniques to elucidate the interactions between
      matrixes and enzyme molecules are also introduced.

PMID- 12049203
TI  - Optimization of glycerol fed-batch fermentation in different reactor states: a
      variable kinetic parameter approach.
AB  - To optimize the fed-batch processes of glycerol fermentation in different reactor
      states, typical bioreactors including 500-mL shaking flask, 600-mL and 15-L
      airlift loop reactor, and 5-L stirred vessel were investigated. It was found that
      by reestimating the values of only two variable kinetic parameters associated
      with physical transport phenomena in a reactor, the macrokinetic model of
      glycerol fermentation proposed in previous work could describe well the batch
      processes in different reactor states. This variable kinetic parameter (VKP)
      approach was further applied to model-based optimization of discrete-pulse feed
      (DPF) strategies of both glucose and corn steep slurry for glycerol fed-batch
      fermentation. The experimental results showed that, compared with the feed
      strategies determined just by limited experimental optimization in previous work,
      the DPF strategies with VKPs adjusted could improve glycerol productivity at
      least by 27% in the scale-down and scale-up reactor states. The approach proposed
      appeared promising for further modeling and optimization of glycerol fermentation
      or the similar bioprocesses in larger scales.

PMID- 12049204
TI  - Optimization of beta-carotene production from synthetic medium by Blakeslea
      trispora: a mathematical modeling.
AB  - The effect of inoculum, pH, carbon and nitrogen source, natural oils, fatty
      acids, antioxidant, and precursors on beta-carotene production by Blakeslea
      trispora in shake-flask culture was investigated. The highest concentration of
      beta-carotene was obtained in the medium (pH 7.0) inoculated with one loop of
      each culture. Sucrose, glycerol, cornmeal, soy protein acid hydrolysate, and
      distiller's solubles did not improve the production of beta-carotene. By
      contrast, glucose, corn steep liquor, antioxidant, olive oil, soybean oil,
      cottonseed oil, oleic and linoleic acids, and kerosene significantly increased
      the beta-carotene production. A central composite design was employed to
      determine the maximum beta-carotene production at optimum values for the process
      variables (linoleic acid, kerosene, and antioxidant). The fit of the model was
      found to be good. Linoleic acid, kerosene, and antioxidant had a strong linear
      effect on beta-carotene production. The concentration of beta-carotene was
      significantly affected by linoleic acid-kerosene and linoleic acid-antioxidant
      interactions as well as by the negative quadratic effects of these variables. The
      interaction between kerosene and antioxidant had no significant linear effect.
      The maximum beta-carotene concentration (2.88 g/L) was obtained at concentrations
      of 17.15 g/L of linoleic acid, 39.25 g/L of kerosene, and 9.04 g/L of
      antioxidant.

PMID- 12049205
TI  - Synergism in binary mixtures of Thermobifida fusca cellulases Cel6B, Cel9A, and
      Cel5A on BMCC and Avicel.
AB  - In an earlier binding study conducted in our laboratory using Thermobifida fusca
      cellulases Cel6B, Cel9A, and Cel5A (formally Thermomonosporafusca E3, E4, and
      E5), it was observed that binding capacities for these three cellulases were 18
      30 times higher on BMCC than on Avicel. These results stimulated an interest in
      how the difference in accessibility between the two cellulosic substrates would
      affect synergism observed with cellulase mixtures. To explore the impact of
      substrate accessibility on the extent of conversion and synergism, three binary
      T. fusca cellulase mixtures were tested over a range of cellulase ratios and
      total molar cellulase concentrations on Avicel and BMCC. Higher extents of
      conversion were observed for BMCC due to the higher enzyme to substrate ratio
      resulting from the higher binding. The processive endoglucanase, Cel9A, had four
      times the extent of conversion of the endocellulase Cel5A, while the exocellulase
      Cel6B had three times the extent of conversion of Cel5A. Approximately 500 nmol/g
      of the Cel9A+Cel6B mixture was needed to obtain 80% conversion, while the
      Cel6B+Cel5A and Cel9A+Cel5A mixtures required 1500 and 1250 nmol/g, respectively,
      to obtain 80% conversion. Thus, it appears that the more accessible structure of
      BMCC, as reflected by its binding capacity, results in relative higher processive
      activity.

PMID- 12049206
TI  - Amphibians as a model for the study of endocrine disruptors.
AB  - Evidence shows that environmental compounds can interfere with the endocrine
      systems of wildlife and humans. The main sink of such substances, called
      endocrine disruptors (EDs), which are mainly of anthropogenic origin, is surface
      water; thus, aquatic vertebrates such as fishes and amphibians are most
      endangered. Despite numerous reports on EDs in fishes, information about EDs in
      amphibians is scarce, and this paucity of information is of particular concern in
      view of the worldwide decline of amphibians. EDs could contribute to changes of
      amphibian populations via adverse effects on reproduction and the thyroid system.
      In amphibians, EDs can affect reproduction by (anti)estrogenic and
      (anti)androgenic modes of action that produce severe effects including abnormal
      sexual differentiation. ED actions on the thyroid system cause acceleration or
      retardation of metamorphosis, which may also affect population levels. Our broad
      knowledge of amphibian biology and endocrinology indicates that amphibians are
      very suitable models for the study of EDs. In particular, effects of EDs on the
      thyroid system triggering metamorphosis can be determined easily and most
      sensitively in amphibians compared to other vertebrates. A new classification of
      EDs according to their biological modes of action is proposed because EDs have
      quite heterogeneous chemical structures, which do not allow prediction of their
      biological effects. Methods and strategies are proposed for identification and
      risk assessment of EDs, whether as pure test substances or as mixtures from
      environmental samples. Effects of EDs on the thyroid system of amphibians can be
      assessed by a single animal model (Xenopus laevis), whereas the various types of
      reproduction need comparative studies to investigate whether general endocrine
      principles do exist among several species of anurans and urodeles. Thus, at least
      one anuran and one urodelean model are needed to determine ED interference with
      reproduction.

PMID- 12049207
TI  - Glycocalyx of lung epithelial cells.
AB  - Due to their diversity and external location on cell membranes, glycans, as
      glycocalyx components, are key elements in eukaryotic cell, tissue, and organ
      homeostasis. Although information on the lung glycocalyx is scarce, this article
      aims to review, discuss, and summarize what is known about bronchoalveolar
      glycocalyx composition, mainly the sialic acids. It was deemed relevant, however,
      to make a brief introductory overview of the cell glycocalyx and its particular
      development in epithelial cells. After that, follows a summary of the evolution
      of the knowledge regarding the bronchoalveolar glycocalyx composition throughout
      the years, particularly its morphological features. Since sialic acids are
      located terminally on the bronchoalveolar lining cells' glycocalyx and play
      crucial roles, we focused mainly on the existing lung histochemical and
      biochemical data of these sugar residues, as well as their evolution throughout
      lung development. The functions of the lung glycocalyx sialic acids are discussed
      and interpretations of their roles analyzed, including those related to the
      negative overall superficial shield provided by these molecules. The increasing
      presence of these sugar residues throughout postnatal lung development should be
      regarded as pivotal in the development and maintenance of a dynamic
      bronchoalveolar architecture, supporting the normal histophysiology of the
      respiratory system. The case for a profound knowledge of lung glycocalyx--given
      its potential to provide answers to serious clinical problems--is made with
      particular reference to cystic fibrosis. Finally, concluding remarks and
      perspectives for future research in this field are put forth.

PMID- 12049208
TI  - Molecular and cellular mechanisms involved in the generation of fiber diversity
      during myogenesis.
AB  - Skeletal muscles have a characteristic proportion and distribution of fiber
      types, a pattern which is set up early in development. It is becoming clear that
      different mechanisms produce this pattern during early and late stages of
      myogenesis. In addition, there are significant differences between the formation
      of muscles in head and those found in rest of the body. Early fiber type
      differentiation is dependent upon an interplay between patterning systems which
      include the Wnt and Hox gene families and different myoblast populations. During
      later stages, innervation, hormones, and functional demand increasingly act to
      determine fiber type, but individual muscles still retain an intrinsic commitment
      to form particular fiber types. Head muscle is the only muscle not derived from
      the somites and follows a different development pathway which leads to the
      formation of particular fiber types not found elsewhere. This review discusses
      the formation of fiber types in both head and other muscles using results from
      both chick and mammalian systems.

PMID- 12049209
TI  - The leukocyte cytoskeleton in cell migration and immune interactions.
AB  - Leukocyte migration is crucial during the development of the immune system and in
      the responses to infection, inflammation, and tumor rejection. The migratory
      behavior of leukocytes under physiological and pathological conditions as well as
      the extracellular cues and intracellular machinery that control and guide
      migration have been studied thoroughly. The cytoskeleton of leukocytes is
      extremely versatile, bearing characteristic features that enable these cells to
      migrate under conditions of flow through narrow spaces and onto target tissues.
      What makes the cytoskeleton machinery so extraordinary is not so much its
      molecular composition, but its flexibility which allows it to display a unique
      combination of responses to the extracellular medium and a rapid regulation of
      the architecture of its components. This review focuses on the cytoskeleton of
      the leukocyte. Its molecular components and the regulation of their assembly and
      organization are discussed. Furthermore, it highlights aspects of the regulation
      of the leukocyte cytoskeleton that confer flexibility to these cells in order to
      perform their specific tasks. Finally, different subcellular structures such as
      the immunological synapse, the uropod of migrating leukocytes, and the phagosome
      displayed by phagocytic cells are discussed in detail. The relationship of the
      leukocyte with its environment occurs through different kinds of receptors that
      interact with ligands that are soluble, fixed on the membrane of other cells, or
      immobilized on the extracellular matrix. The impact of receptor-ligand binding on
      the functional responses and the rearrangement of the cytoskeleton is also
      examined.

PMID- 12049210
TI  - Structure and function of the Entamoeba histolytica Gal/GalNAc lectin.
AB  - Gal/GalNAc lectin is a novel multifunctional virulence factor of the human
      parasite Entamoeba histolytica. The native protein is a 260-kDa heterodimer
      consisting of a type 1 membrane protein disulfide bonded to a lipid-anchored
      protein. Each subunit has several isoforms that may form functionally different
      heterodimers, analogous to the integrin family of proteins. Recently a second 150
      kDa Gal/GalNAc lectin has been identified in E. histolytica that associates with
      the 260-kDa lectin. The functions of the 260-kDa lectin have been characterized
      using specific monoclonal antibodies. This lectin plays roles in many of the
      critical aspects of this parasite's pathogenicity including adherence, cytolysis,
      invasion, resistance to lysis by complement, and also perhaps encystment. Current
      knowledge regarding both the structure and function of this unique
      multifunctional virulence factor are discussed.

PMID- 12049212
TI  - Further sesquiterpenes from Polygonum viscosum (Polygonaceae).
AB  - Two new sesquiterpenes, 4-methoxycarbonyl-7-(1-methylethyl)-6-oxo-3,3a,7,8,8a
      pentahydroazulene-1-carboxylic acid (viscoazusone) and 1,4-dimethoxy-carbonyl-7
      (1-methylethyl)-6-oxo-3,3a,7,8,8a-pentahydroazulene (viscoazulone), were isolated
      from the whole plant of Polygonum viscosum. The structures of these compounds
      were determined by spectroscopic means.

PMID- 12049211
TI  - Epigenetic mechanisms for primary differentiation in mammalian embryos.
AB  - This review examines main developments related to the interface between primary
      mammalian cell differentiation and various aspects of chromosomal structure
      changes, such as heterochromatin dynamics, DNA methylation, mitotic
      recombination, and inter- and intrachromosomal differentiation. In particular, X
      chromosome difference, imprinting, chromosomal banding, methylation pattern,
      single-strand DNA breaks, sister chromatid exchanges (SCEs), and sister chromatid
      asymmetry are considered. A hypothesis is put forward which implies the existence
      of an epigenetic asymmetry versus mirror symmetry of sister chromatids for any
      DNA sequences. Such epigenetic asymmetry appears as a result of asymmetry of
      sister chromatid organization and of SCE and is a necessary (not sufficient)
      condition for creating cell diversity. The sister chromatid asymmetry arises as a
      result of consecutive rounds of active and passive demethylation which leads
      after chromatin assembly events to chromatid difference. Single-strand DNA breaks
      that emerge during demethylation trigger reparation machinery, provend as sister
      chromatid exchanges, which are not epigenetically neutral in this case. Taken
      together, chromatid asymmetry and SCE lead to cell diversity regarding their
      future fate. Such cells are considered pluripotent stem cells which after
      interplay between a set of chromosomal domains and certain substances localized
      within the cytoplasmic compartments (and possibly cell interactions) can cause
      sister cells to express different gene chains. A model is suggested that may be
      useful for stem cell technology and studies of carcinogenesis.

PMID- 12049214
TI  - Nitrotyrasacutuminine from Menispermum dauricum.
AB  - Nitrotyrasacutuminine, an unusual nitrated morphine-type alkaloid was isolated
      from the roots of Menispermum dauricum. Its structure was determined by various
      2D spectra and chemical methods.

PMID- 12049213
TI  - Three new hydroxylated serratidine alkaloids from Huperzia serrata.
AB  - A known compound, serratidine (1), along with three hydroxylated serratidine
      alkaloids, 6alpha-hydroxyserrati dine (2), 4alpha-hydroxyserratidine (3) and
      4alpha,6alpha-dihydroxyserratidine (4) were isolated from the CHCl3 fraction of
      basic materials of whole plant of the Chinese medicinal herb Huperzia serrata.
      The relative configurations of the above compounds were determined based on 2D
      NMR studies.

PMID- 12049215
TI  - Triterpene saponins from Craniotome furcata.
AB  - Three saponins, craniosaponin A (1) and buddlejasaponins Ia (2) and I (3) were
      isolated from the n-butanol soluble fraction of Craniotome furcata for the first
      time. Among them, craniosaponin A (1) was identified to be a new compound. The
      structure of craniosaponin A was assigned mainly by spectral methods. A
      preliminary assay in vitro was applied to evaluate their cytotoxicity against
      several tumor cell-lines.

PMID- 12049216
TI  - Two new cyclic bis(bibenzyl)s, isoriccardinquinone A and B from the liverwort
      Marchantia paleacea.
AB  - From the 95% ethanol extract of the Hong Kong liverwort, Marchantiapaleacea,
      guided by bioactivity directed isolation, two novel isoriccardinquinones A and B
      were obtained together with previously known marchantin C, isoriccardin C and
      phenanthrene derivative, 2-hydroxy-3,7-dimethoxyphenanthrene. The structures of
      the new compounds were established by high field spectroscopic methods, including
      2D NMR techniques.

PMID- 12049217
TI  - Triterpenoids from Psidium guajava leaves.
AB  - Three pentacyclic triterpenoids including one new guajavanoic acid (2) and two
      known obtusinin (1) and goreishic acid I (3) have been isolated from the leaves
      of Psidium guajava. The new constituent 2 has been characterized as 2alpha
      hydroxy-3beta-p-E-coumaroyloxyurs-12, 18-dien-28-oic acid through 1H-NMR and 13C
      NMR (broad band and DEPT). This is the first report of isolation of compound 1
      and 3 from the genus Psidium.

PMID- 12049218
TI  - Gnapholide: a new guaiac-dimer from Pulicaria gnaphalodes (Asteraceae).
AB  - The ethyl acetate soluble part of the chloroform extract of Pulicaria gnaphalodes
      belonging to the family Asteraceae afforded a new sesquiterpene-dimer of guaiane
      class named as gnapholide and anabsinthin of the same skeleton. The structures of
      both the compounds were elucidated with the aid of spectroscopic techniques
      including 2D NMR.

PMID- 12049220
TI  - Marruboside, a new phenylethanoid glycoside from Marrubium vulgare L.
AB  - A new phenylethanoid glycoside, marruboside, has been isolated from the aerial
      parts of Marrubium vulgare L. Its structure was established as 3,4-dihydroxy-beta
      phenylethoxy-O-[beta-D-apiofuranosyl-(1-->2)-alpha-L-rhamnopyranosyl-(1-->3)]
      [beta-D-apiofuranosyl-(1-->6)]-4-O-caffeoyl-beta-D-glucopyranoside, on the basis
      of spectroscopic evidence.

PMID- 12049219
TI  - Synthesis, dimerization, and biological activity of hexaoxygenated chalcones
      related to calythropsin and combretastatins.
AB  - Five new hexaoxygenated chalcones and one new chalcone photodimer were
      synthesized and their cytotoxicity against leukemia cell line L-1210 was studied.
      The three more active compounds were tested for their activity on the inhibition
      and promotion of tubulin assembly and it was found that these chalcones do not
      interfere with the tubulin-microtubule system at cytotoxic concentrations, and
      therefore operate by some different mechanism of action.

PMID- 12049221
TI  - Synthesis and antioxidant activity of 3-substituted guaiazulene derivatives.
AB  - A series of 3-substituted guaiazulene derivatives has been synthesized and their
      antioxidant properties were evaluated by monitoring their capacity for scavenging
      the stable free-radical DPPH. 3-Vinylguaiazulene was the most potent, possessing
      antioxidant activity superior than alpha-tocopherol. These derivatives were also
      moderate inhibitors of the proliferation of human promyelocytic leukemia cells.

PMID- 12049222
TI  - Structure elucidation of a novel funicone-like compound produced by Penicillium
      pinophilum.
AB  - A novel metabolite related to the previously identified compound 3-O
      methylfunicone (1) was isolated from the fungus Penicillium pinophilum and its
      structure elucidated by spectral analysis as 3-O-methyl-5, 6-epoxyfunicone (2).

PMID- 12049223
TI  - Effect of predator diet on life history shifts of red-legged frogs, Rana aurora.
AB  - Larval red-legged frogs (Rana aurora) are known to exhibit antipredator behavior
      in response to both chemical alarm cues released from injured conspecifics and
      chemical cues of predators. In some cases, the response to predators is dependent
      on the predator's diet. In this experiment, we tested whether long-term exposure
      to predator chemical cues and alarm cues resulted in alteration of life history
      characteristics of red-legged frogs. We raised groups of tadpoles in the presence
      of chemical cues of predators that were either fed conspecifics or heterospecific
      caddis-fly larvae, chemical cues of injured conspecifics, or a no-cue control.
      Tadpoles raised in the presence of either a predator fed conspecifics or cues of
      injured conspecifics metamorphosed earlier and at a smaller size than those
      exposed to predators fed heterospecifics or the no-cue control. The result
      suggests that red-legged frogs exhibit a life history shift in response to
      predatory cues and that this response is dependent on the diet of predators.

PMID- 12049224
TI  - Prey detection by vomeronasal chemoreception in a plethodontid salamander.
AB  - While chemoreception is involved in a wide variety of salamander behaviors, the
      chemosensory system that mediates specific behaviors is rarely known. We
      investigated the role of the vomeronasal system (VNS) in foraging behavior of the
      red-backed salamander (Plethodon cinereus) by manipulating salamanders' abilities
      to detect nonvolatile chemical cues emitted by potential prey. Subjects received
      one of three treatments: (1) impaired vomeronasal system, (2) sham manipulation,
      and (3) no manipulation. The role of the VNS in mediating foraging on motile prey
      (Drosophila melanogaster) was investigated under three light conditions (bright,
      dim, dark). Salamanders with impaired VNSs foraged less efficiently than either
      of the other experimental groups by displaying the longest latency to attack and
      the lowest rate of prey capture, especially in the absence of visual cues. A
      second experiment utilized freshly killed prey to determine whether the VNS takes
      on added importance in the absence of visual or tactile cues associated with
      moving prey. Animals with impaired VNSs showed a decreased foraging efficiency on
      stationary prey under both dark and light conditions. In addition, a mark
      recapture study of VNS-impaired and sham salamanders in the field also indicated
      that salamanders with impaired VNSs consumed fewer stationary prey compared to
      shams. The study indicates that the VNS plays a substantial role in the foraging
      behavior of the plethodontid salamander, P. cinereus.

PMID- 12049225
TI  - Evaluation of synthetic hydrocarbons for mark-recapture studies on the red
      milkweed beetle.
AB  - This study evaluates the potential for using blends of synthetic hydrocarbons in
      mark-recapture studies of insects. To test the durability of hydrocarbons, we
      applied a blend of five straight-chain hydrocarbons (C24, C21, C26. C28, C30) to
      detached elytra of the red milkweed beetle, Tetraopes tetrophthalmus (Forster)
      (Coleoptera: Cerambycidae), mounted the elytra on pins, and placed them in an
      exposed location outdoors. The amount of hydrocarbons on the elytra did not
      change over time, even after two months of exposure to sun and rain. Synthetic
      hydrocarbons applied to the elytra of living beetles did not significantly
      influence their longevity or mating success in a laboratory study. and the
      amounts of hydrocarbons did not change with age. The invariability of hydrocarbon
      ratios over time suggests that blends could provide a nearly infinite variety of
      ratios to mark individual insects uniquely and indelibly with a hydrocarbon
      "fingerprint." This technique offers a convenient, safe, and durable means of
      individually marking insects and may find application in field studies of larger
      bodied insects that are long-lived and sedentary.

PMID- 12049226
TI  - Evidence for a sex pheromone in bark beetle parasitoid Roptrocerus xylophagorum.
AB  - Male Roptrocerus xylophagorum (Ratzeburg) (Hymenoptera: Pteromalidae) exhibited
      courtship and mating behaviors including wing fanning, antennation, mounting, and
      copulation attempts when exposed to glass bulb decoys coated with a whole-body
      extract of females in hexane, acetone, or methanol. Activity of extract-treated
      decoys declined gradually over one week. Males responded much less strongly to
      freeze-killed female cadavers extracted with solvents than to unextracted
      cadavers; treatment of extracted cadavers with female extract restored male
      responses. The pheromone was found to be equally present over the surface of both
      the abdomen and head/thorax of females, and the origin of the pheromone could not
      be conclusively localized to any single body region. The activity of pheromone on
      females increased between day 1 and days 3-5 following eclosion; otherwise,
      pheromone activity was not significantly affected by either female age or mating.
      Males were arrested within the zone of a glass surface on which females had
      walked, suggesting that the pheromone might be substrate-borne. Recent exposure
      to females reduced male responsiveness, but responsiveness was fully restored
      after a few hours of male isolation from females. When hexane extracts of whole
      females were fractionated on silica gel, the pheromone's activity was largely
      recovered with the first, most nonpolar fraction. Female extracts and fractions
      were analyzed by coupled gas chromatography-mass spectrometry. Cuticular
      hydrocarbon alkanes were identified as the extract components whose
      concentrations correlated best with male responses. Evidence of the pheromone's
      long persistence, low volatility, low polarity, and presence over the insect's
      entire body surface further supported the hypothesis that the pheromone was
      composed of one or more cuticular hydrocarbons.

PMID- 12049227
TI  - Evidence for a compound in Comstock-Kellog glands modulating premating behavior
      in male desert locust, Schistocerca gregaria.
AB  - The Comstock-Kellog glands in adult females of certain acridid species, including
      the desert locust, Schistocerca gregaria have been implicated as a source of
      volatiles that play a role in mating behavior. A dichloromethane extract of the
      glands was analyzed for metabolites by gas chromatography, coupled gas
      chromatography-electroantennographic detection, and mass spectrometry. Coupled
      gas chromatography-electroantennographic detector (GC-EAD) analysis revealed a
      component that elicited an electroantennogram response from the antenna of adult
      male S. gregaria. The compound was identified by GC-MS as pentanoic acid. The
      levels of the compound in the gland extract varied with age of female locust; it
      was present in detectable amounts only in 14- to 16-day-old females. In
      bioassays, pentanoic acid significantly stimulated pre-mating behavior in male
      desert locust. These results are discussed in relation to the biology of the
      locust.

PMID- 12049228
TI  - Peripheral coding of sex pheromone and a behavioral antagonist in the Japanese
      beetle, Popillia japonica.
AB  - Male antennae of the Japanese beetle, Popillia japonica, possess olfactory
      receptor neurons (ORNs) cocompartmentalized in the same sensilla placodea, one
      tuned to the sex pheromone, (R)-japonilure, and the other to the detection of a
      behavioral antagonist, (S)-japonilure. In-depth electrophysiological experiments
      revealed mutual inhibitory and synergistic effects in ORNs stimulated
      simultaneously with the two semiochemicals. The olfactory system of P japonica
      exhibited a remarkable ability to discriminate completely coincident strands of
      pheromone and behavioral antagonist from strands of the two semiochemicals
      temporally isolated (by 1.5-3 msec). The mutual inhibition was reflected mainly
      by the delay of onset or total lack of spikes and by the significant increase in
      the rise time of potentials generated by blends of (R)- and (S)-japonilure. In
      contrast, synergist ORNs showed no neural activity (spikes) when stimulated with
      either the sex pheromone or the behavioral antagonist, but showed clear responses
      to blends of the two semiochemicals. Evidence for mixture-suppressed responses
      was observed not only in the Japanese beetle, but also in the Osaka beetle,
      Anomala osakana, and the Oriental beetle, Exomala orientalis, thus suggesting
      that it is a common feature in the sensory physiology of scarab beetles.

PMID- 12049229
TI  - Postgenomic chemical ecology: from genetic code to ecological interactions.
AB  - Environmental response genes are defined as those encoding proteins involved in
      interactions external to the organism, including interactions among organisms and
      between the organism and its abiotic environment. The general characteristics of
      environmental response genes include high diversity, proliferation by duplication
      events, rapid rates of evolution, and tissue- or temporal-specific expression.
      Thus, environmental response genes include those that encode proteins involved in
      the manufacture, binding, transport, and breakdown of semiochemicals. Postgenomic
      elucidation of the function of such genes requires an understanding of the
      chemical ecology of the organism and, in particular, of the "small molecules"
      that act as selective agents either by promoting survival or causing selective
      mortality. In this overview, the significance of several groups of environmental
      response genes is examined in the context of chemical ecology. Cytochrome P-450
      monooxygenases provide a case in point; these enzymes are involved in the
      biosynthesis of furanocoumarins (furocoumarins), toxic allelochemicals, in
      plants, as well as in their detoxification by lepidopterans. Biochemical
      innovations in insects and plants have historically been broadly defined in a
      coevolutionary context. Considerable insight can be gained by defining with
      greater precision components of those broad traits that contribute to
      diversification. Molecular approaches now allow chemical ecologists to
      characterize specifically those biochemical innovations postulated to lead to
      adaptation and diversification in plant/insect interactions.

PMID- 12049230
TI  - The role of monoterpenes in resistance of Douglas fir to western spruce budworm
      defoliation.
AB  - We conducted defoliation experiments with 7- to 8-year-old clones of Douglas fir
      [Pseudotsuga menziesii (Mirb.) Franco var. glauca] to assess the role of
      monoterpenes as a resistance mechanism to western spruce budworm (Choristoneura
      occidentalis Freeman) defoliation. The grafted clones were derived from mature
      trees that showed resistance or susceptibility to budworm defoliation in the
      forest. All clones were exposed to either budworm defoliation or nondefoliation
      treatments in 1998 and 1999 under greenhouse conditions. We found that the total
      concentration of monoterpenes in current-year foliage varied greatly between two
      consecutive years in clones in the greenhouse and in their corresponding mature
      trees in the forest. Fractional composition of different monoterpenes was similar
      between different years and between clones and mature trees, indicating genetic
      control of this trait. Two different defoliation experiments were conducted to
      assess the importance of budburst phenology as a factor determining host plant
      resistance. In the 1998 experiment, budworm feeding was matched to the budburst
      of each individual plant. Monoterpene concentration was high in 1998, and budworm
      potential fitness was greater on clones from the resistant mature trees that had
      lower concentrations of total monoterpenes. In the 1999 experiment, budworm
      feeding was matched to budburst of the whole population of plants in order to
      mimic conditions similar to insects feeding on trees in the field. The
      concentration of monoterpenes was low in 1999, and budworm fitness was not
      related to monoterpenes. Total monoterpene concentration was negatively related
      to foliar nitrogen concentration, suggesting that C/N balance may affect
      monoterpene synthesis in needles. However, tree growth was not related to total
      monoterpene concentration. We concluded that expression of differences in budworm
      resistance among Douglas fir genotypes might be caused by interactions among
      multiple resistance mechanisms such as needle monoterpenes and tree budburst
      phenology.

PMID- 12049231
TI  - Effects of large mammalian herbivores and ant symbionts on condensed tannins of
      Acacia drepanolobium in Kenya.
AB  - Condensed tannins have been considered to be important inducible defenses against
      mammalian herbivory. We tested for differences in condensed tannin defenses in
      Acacia drepanolobium in Kenya over two years among different large mammalian
      herbivore treatments [total exclusion, antelope only, and megaherbivore
      (elephants and giraffes) + antelope] and with four different ant symbiont species
      on the trees. We predicted that (1) condensed tannin concentrations would be
      lowest in the mammal treatment with the lowest level of herbivory (total
      exclusion), (2) trees occupied by mutualist ants that protect the trees most
      aggressively would have lower levels of tannins, and (3) if chemical defense
      production is costly, there would be a trade-off between tannin concentrations,
      growth, and mechanical defenses. Mean tannin concentrations increased from total
      exclusion treatments to wildlife-only treatments to megaherbivore + antelope
      treatments. In 1997, condensed tannin concentrations were significantly lower in
      trees occupied by the ant Crematogaster nigriceps, the only ant species that
      actively removed axillary buds. Contrary to our prediction, trees occupied by ant
      species that protect the trees more aggressively against mammalian herbivores did
      not have lower overall levels of condensed tannins. There was no consistent
      evidence of a trade-off between tannin concentrations and growth rate, but there
      was a positive correlation between mean thorn length and mean tannin
      concentrations across species of ant inhabitants and across herbivore treatments
      in 1997. Contrary to our expectation, trees had higher tannin concentrations in
      the upper parts of the canopy where there is little herbivory by mammals.

PMID- 12049232
TI  - Does decreased mowing frequency enhance alkaloid production in endophytic tall
      fescue and perennial ryegrass?
AB  - Tall fescue, Festuca arundinacea, and perennial ryegrass, Lolium perenne. are
      widely infected with fungal endophytes (Neotyphodium spp.). The symbiosis between
      plant and fungus leads to synthesis of alkaloids that have been shown to be
      either toxic or act as feeding deterrents against insect pests. As cultural
      practices have the potential to regulate production of plant secondary
      metabolites, we evaluated the influence of mowing frequency on the levels of
      major alkaloids in tall fescue and perennial ryegrass in the greenhouse. Tall
      fescue and perennial ryegrass maintained in 15-cm-diam. pots were cut to 5-cm
      height weekly or biweekly. Samples were taken monthly and the alkaloids extracted
      and analyzed by reverse-phase LC-MS. In tall fescue, ergovaline, ergonovine, and
      ergocristine were identified, whereas only ergocristine was identified in
      perennial ryegrass samples. In tall fescue, we observed a trend showing higher
      levels in samples cut biweekly than in those cut weekly. A similar pattern was
      seen in some putative alkaloids that were not identified. In perennial ryegrass,
      ergocristine and two putative alkaloids followed a pattern similar to that of
      alkaloids in tall fescue. A survey of a few samples of perennial ryegrass using
      extractions specific to peramine and lolitrem B yielded evidence suggesting their
      presence as well as several other identified alkaloids. These data support the
      hypothesis that decreased mowing frequency enhances alkaloid
      production/accumulation in tall fescue and perennial ryegrass.

PMID- 12049233
TI  - Differential attractiveness of induced odors emitted by eight maize varieties for
      the parasitoid cotesia marginiventris: is quality or quantity important?
AB  - Herbivore-induced plant volatiles can function as indirect defense signals that
      attract natural enemies of herbivores. Several parasitoids are known to exploit
      these plant-provided cues to locate their hosts. One such parasitoid is the
      generalist Cotesia marginiventris, which is, among others, attracted to maize
      volatiles induced by caterpillar damage. Maize plants can be induced to produce
      the same blend of attractive volatiles by treating them with regurgitant of
      Spodoptera species. We collected and analyzed the regurgitant-induced emissions
      of two plant species (cowpea and maize) and of eight Mexican maize varieties and
      found significant differences among their volatile emissions, both in terms of
      total quantity and the quality of the blends. In a Y-tube olfactometer. the odors
      of the same artificially induced plant species and Mexican varieties were offered
      in dual choice experiments to naive mated females of C. marginiventris. Wasps
      preferred cowpea over maize odor and, in 3 of 12 combinations with the maize
      varieties, they showed a preference for the odors of one of the varieties, A
      comparison of the odor collection with results from the behavioral assays
      indicates that not only the quantity of the volatile emissions, but also the
      quality (composition) of the volatile blends is important for attraction of C.
      marginiventris. The results are discussed in the context of the possibility of
      breeding crop varieties that are particularly attractive to parasitoids.

PMID- 12049234
TI  - Odor composition of preferred (buffalo and ox) and nonpreferred (waterbuck) hosts
      of some Savanna tsetse flies.
AB  - A previous study on the feeding responses of tsetse flies, Glossina morsitans
      morsitans, implicated the existence of allomonal barriers, both volatile and
      nonvolatile, on the nonpreferred host, waterbuck, Kobus defassa. In the present
      study, electroantennogram-active compounds in odors from waterbuck were compared
      with those of two preferred hosts of tsetse flies, buffalo, Syncerus caffer, and
      ox, Bos indicus. Odors from the three bovids were trapped on activated charcoal
      and/or reverse-phase (octadecyl bonded) silica and analyzed with a gas
      chromatography-linked electroantennographic detector (GC-EAD) and, where
      possible, identified by using gas chromatography-linked mass spectrometry (GC-MS)
      and chromatographic comparisons with authentic samples. The GC-EAD profiles (with
      G. m. morsitans antennae) of the odors of the two preferred hosts were
      comparable, comprising medium-chain, saturated or unsaturated aldehydes and
      phenols, with buffalo emitting a few more EAG-active aldehydes. Waterbuck odor
      gave a richer profile, consisting of fewer aldehydes but more phenolic components
      and a series of 2-ketones (C-C13) and delta-octalactone. This bovid also emits
      moderate amounts of C5-C9 straight-chain fatty acids, some of which were detected
      in buffalo and ox only in trace amounts. However, these did not elicit
      significant GC-EAD responses. Waterbuck profiles from the antennae of G.
      pallidipes showed broad similarity to those from G. m. morsitans, although the
      composition of aldehydes and ketones was somewhat different, indicating species
      specific difference in the detection of host odors. Certain waterbuck-specific
      EAG-active components, particularly the 2-ketones and lactone, constitute a
      candidate allomonal blend in waterbuck odor.

PMID- 12049235
TI  - Taste sensitivity of detritivorous mosquito larvae to decomposed leaf litter.
AB  - Dietary leaf litter chemistry is known to play an important ecotoxicological role
      in the plant-mosquito interaction in subalpine flooded areas surrounded by
      vegetation because of differential larvicidal effects of insoluble polyphenols
      formed during the leaf decaying process. This dietary interaction was
      investigated through comparative evaluation of the role of toxic/nontoxic leaf
      litter in both larval foraging and feeding behavior, by using different samples
      of decomposed alder leaf litter and larval Aedes aegypri as experimental
      references. Track analysis showed significant differences in larval foraging
      behavior in the absence or presence of leaf litter. Comparative alimentary
      preference investigations and further track analysis suggested that larvae are
      unable to detect leaf litter toxicity. These characteristics of the larval
      behavioral feeding pattern suggested that: (1) decomposed leaf litter may be
      involved as an important attractive food source in the habitat selection and
      evolutionary history of culicids, and (2) preingestive behavioral mechanisms
      appear to be minimally involved in the differential larval dietary adaptation to
      toxic leaf litter. These results may have interesting consequences for culicid
      biological control.

PMID- 12049237
TI  - Comparing objective and subjective learning curves: judgments of learning exhibit
      increased underconfidence with practice.
AB  - When participants studied a list of paired associates for several study-test
      cycles, their judgments of learning (JOLs) exhibited relatively good calibration
      on the 1st cycle, with a slight overconfidence. However, a shift toward marked
      underconfidence occurred from the 2nd cycle on. This underconfidence-with
      practice (UWP) effect was very robust across several experimental manipulations,
      such as feedback or no feedback regarding the correctness of the answer, self
      paced versus fixed-rate presentation, different incentives for correct
      performance, magnitude and direction of associative relationships, and conditions
      producing different degrees of knowing. It was also observed both in item-by-item
      JOLs and in aggregate JOLs. The UWP effect also occurred for list learning and
      for the memory of action events. Several theoretical explanations for this
      counterintuitive effect are discussed.

PMID- 12049236
TI  - The putative role of botrydial and related metabolites in the infection mechanism
      of Botrytis cinerea.
AB  - Phytotoxic assays, performed both in vitro and in vivo on leaves of Phaseolus
      vulgaris, with metabolites excreted by the fungus B. cinerea are evaluated.
      Exogenous application of the phytotoxin botrydial has been found to produce
      severe chlorosis and cell collapse and facilitated fungal penetration and
      colonization of plant tissue. The results also show a light-dependent action
      mechanism for the phytotoxin and seem to indicate that botrydial is a non-host
      specific toxin involved in fungal infection of B. cinerea.

PMID- 12049238
TI  - Simplified learning in complex situations: knowledge partitioning in function
      learning.
AB  - The authors explored the phenomenon that knowledge is not always integrated and
      consistent but may be partitioned into independent parcels that may contain
      mutually contradictory information. In 4 experiments, using a function learning
      paradigm, a binary context variable was paired with the continuous stimulus
      variable of a to-be-learned function. In the first 2 experiments, when context
      predicted the slope of a quadratic function, generalization was context specific.
      Because context did not predict function values, it is suggested that people use
      context to gate separate learning of simpler partial functions. The 3rd
      experiment showed that partitioning also occurs with a decreasing linear
      function, whereas the 4th study showed that partitioning is absent for a linearly
      increasing function. The results support the notion that people simplify complex
      learning tasks by acquiring independent parcels of knowledge.

PMID- 12049239
TI  - Lower region: a new cue for figure-ground assignment.
AB  - Figure-ground assignment is an important visual process; humans recognize, attend
      to, and act on figures, not backgrounds. There are many visual cues for figure
      ground assignment. A new cue to figure-ground assignment, called lower region, is
      presented: Regions in the lower portion of a stimulus array appear more
      figurelike than regions in the upper portion of the display. This phenomenon was
      explored, and it was demonstrated that the lower-region preference is not
      influenced by contrast, eye movements, or voluntary spatial attention. It was
      found that the lower region is defined relative to the stimulus display, linking
      the lower-region preference to pictorial depth perception cues. The results are
      discussed in terms of the environmental regularities that this new figure-ground
      cue may reflect.

PMID- 12049240
TI  - Reaching while calculating: scheduling of cognitive and perceptual-motor
      processes.
AB  - To address the neglected question of how cognitive and perceptual-motor processes
      are coordinated, the authors asked participants to move a cursor from one target
      to another to reveal operators and operands for a running arithmetic task. In
      Experiment I performance on this task was compared with performance on tasks
      requiring only aiming or only arithmetic. Aiming was faster in the aiming-only
      task than in the combined task. More importantly, times for steps requiring
      calculation were equivalent in the combined and arithmetic-only tasks. The
      results from this and a second experiment suggest that participants slowed their
      aiming to allow calculations to be completed before subsequent targets were
      entered. As a whole, the results suggest that cognitive and perceptual-motor
      processes are coordinated through scheduling.

PMID- 12049241
TI  - Visual attention and word recognition in stroop color naming: is word recognition
      "automatic"?
AB  - In Stroop color naming, color targets were accompanied by a color word or a color
      word plus a neutral word that reduces or "dilutes" the Stroop effect. Abrupt
      onset cues called the focus of attention to one stimulus or another. Cuing
      influenced the size of the Stroop effect but never eliminated it. Unlike the
      Stroop effect itself, Stroop dilution from the neutral word could be eliminated,
      by cuing the color word. Focusing visual attention on the color word protected it
      from Stroop dilution; focusing visual attention on the neutral word did not
      prevent Stroop interference. Thus, spatial attention is a modulator, protecting
      visual data from crosstalk, but a word need not be the focus of visual attention
      to be recognized.

PMID- 12049242
TI  - Separating sensitivity from response bias: implications of comparisons of yes-no
      and forced-choice tests for models and measures of recognition memory.
AB  - A fundamental challenge to psychological research is the measurement of cognitive
      processes uncontaminated by response strategies resulting from different testing
      procedures. Test-free estimates of ability are vital when comparing the
      performance of different groups or different conditions. The current study
      applied several sets of measurement models to both forced-choice and yes-no
      recognition memory tests and concluded that the traditional signal-detection
      model resulted in distorted estimates of accuracy. Two-factor models were
      necessary to separate memory sensitivity from response bias. These models
      indicated that (a) memory accuracy did not differ across the tests and (b) the
      tests relied on the same underlying memory processes. The results illustrate the
      pitfalls of using a single-component model to measure accuracy in tasks that
      reflect 2 or more underlying processes.

PMID- 12049243
TI  - The negative compatibility effect: unconscious inhibition influences reaction
      time and response selection.
AB  - In the negative compatibility effect (NCE) a masked prime arrow, pointing left or
      right, is followed by an unmasked (visible) target arrow. The task is to press
      the left or right switch corresponding to the visible arrow. Surprisingly,
      reaction time is longer (slowed) when the prime and target indicate the same,
      rather than different, responses. By contrast, the effect of an unmasked prime is
      positive-opposite to the NCE. This indicates that the NCE is not attributable to
      incomplete masking; to the extent that the prime is visible, the NCE would be
      reduced by this positive influence. Thus, the NCE appears to result from
      unconscious processing of the prime and, in that sense, may be a form of
      subliminal perception. Additional findings show that the NCE is due to inhibition
      of a response code, that it is automatic in that it occurs even if the
      information in the prime and target could be ignored, and that it also influences
      response selection.

PMID- 12049244
TI  - Magnitude comparisons distort mental representations of magnitude.
AB  - Many cognitive processes rely on representations of magnitude, yet these
      representations are often malleable (H. Helson, 1964; J. Huttenlocher, L. V.
      Hedges, & J. L. Vevea, 2000; A. Parducci, 1965). It is likely that factors that
      affect these representations in turn affect the psychological processes that rely
      on them. The authors conducted 4 experiments to investigate whether language
      expressible magnitude comparisons distort mental representations of compared
      magnitudes. Participants compared magnitudes and estimated those magnitudes in a
      variety of tasks. Experiments 1 through 3 demonstrated systematic comparison
      induced distortions. Experiment 4 demonstrated that comparison-induced
      distortions might account for the asymmetric dominance effect discussed in the
      decision-making literature. Potential effects of comparison-induced distortions
      on other psychological processes (e.g., density effects, order effects, body-size
      estimation, pain estimation, and consumer decision making) are discussed.

PMID- 12049245
TI  - On the misperception of variability.
AB  - It has long been claimed that people perceive the world as less variable and more
      regular than it actually is. Such misperception, if shown to exist, could explain
      some perplexing behaviors. However, evidence supporting the claim is indirect,
      and there is no explanation of its cause. As a possible cause, the authors
      suggest that people use sample variability as an estimate of population
      variability. This is so because the sampling distribution of sample variance is
      downward attenuated, the attenuation being substantial for sample sizes that
      people consider. Results of 5 experiments show that people use sample
      variability, uncorrected for sample size, in tasks in which a correction is
      normatively called for, and indeed perceive variability as smaller than it is.

PMID- 12049246
TI  - Survey of faecal parasites in patients from western Kenya.
AB  - Faecal specimens were collected from patients complaining of diarrhoea and
      abdominal or epigastric discomfort at two hospitals. Information obtained by
      questionnaires completed at the time of specimens collection, included
      demographic and clinical data. Specimens were preserved in 10% formalin and
      polyvinyl alcohol (PVA) and examined, as wet mounts and stained with Wheatley's
      Trichrome, Weber, modified acid-fast and hot safranin stains. One hundred
      patients were examined, in 30 of them parasites were detected. The most common
      organism identified was Cryptosporidium parvum, in specimens of five patients,
      followed by Entamoeba histolytica/E. dispar in four patients. The recently
      described "emerging parasites" were detected. Helminth eggs were found in two
      patients only. HIV status was not known for most of the patients, and the
      parasites commonly proliferate in the immuno-compromised individuals were not
      frequently found.

PMID- 12049247
TI  - Fasciola immature stages sought in Lymnaea species and Biomphalaria species in
      the water bodies of Dakahlia Governorate.
AB  - Examination of the five different water bodies in Dakahlia governorate, revealed
      four species of Lymnaea. These were L. natalensis (68.4%). L. truncatula (16%),
      L. stagnalis (12.2%) and L. columella (3.4%). Also, two species of Biomphalaria
      were recovered. These were B. alexandrina (54.7%) and B. glabrata (45.3%).
      Examination of all these snails showed natural infection with immature stages of
      Fasciola sp. in 5.5% of L. natalensis (= cailliaudi), 3.1% in L. truncatula and
      0.67% in B. alexandrina. The importance of these snails in dissemination and
      spreading of fascioliasis was discussed.

PMID- 12049248
TI  - The endoparasites of sheep and goats, and shepherd in North Sinai Governorate,
      Egypt.
AB  - Examination of sheep and goats in four areas in North Sinai revealed an overall
      infection of 12.70% with Fasciola species, 11.8% with Paramphistomum cerve,
      12.80% with Moniezia expansa, 47.11% with Trichostrongylus colubriformis, 4.59%
      Trichuris ovis and 44.85% Coccidia. The highly infected sheep and goats were
      diagnosed in El Hassanah center (90.49%), followed by Al Arish city (87.31%),
      then Rafah city (74.39%), and lastly Bir Al Abd (54.71%). The elevation of the
      overall percent of infection in the four areas was due to Coccidia infection.
      This parasite was a concomitant infection in nearly all animals. On the other
      hand, examination of fifteen of the shepherds revealed Ascaris lumbricoides in
      four, T. colubriformis in three, Fasciala in one, Giardia lamblia in ten and
      Coccidia in three. Double and rarely, triple infection was seen. The correlation
      between parasitic infections in sheep and goats, and their shepherd was
      discussed.

PMID- 12049249
TI  - Morphological and histological observations on male of genus Paragorgorhynchus
      (Acanthocephala) with special reference to reproductive system.
AB  - The general morphology of Paragorgorhynchus aswanensis was studied by the
      scanning electron microscope and by histological examination. The major areas
      studied were proboscis and the receptacle with the associated muscles, the nerve
      ganglion with the retinacular nerve cells and the lemnisci. The details of
      genital system in whole mount preparation and photomicrographs of cross-section
      from wax preparation are depict, with morphological changes along the length of
      the mature male worm.

PMID- 12049250
TI  - Intestinal capillariass in Egypt epideiologigal background.
AB  - Intestinal capillariasis has been reported in Egypt in 1989. Since that time, 44
      cases have been diagnosed. Most of the detected cases were females (37), while
      males were only 7. Their ages ranged from 10 to 65 years, however most of them
      were between 20 to 40 years. Twenty-six cases were from the northern part of
      Upper Egypt, particularly Bani-Suif and El-Menia Governorates. Patients presented
      with borborygmi, chronic diarrhea, vomiting, loss of weight, lower limb edema and
      electrolyte imbalance for durations ranging from one month to two years.
      Morbidity and mortality of the disease in Egyptian cases are described. Some
      patients gave history of eating raw whole fish, while others gave history of
      eating raw parts of fish or half-cooked fish. Diagnosis was based on the clinical
      picture, and confirmed stool analysis. Differential diagnosis was discussed and
      the cost paid by patients to reach the correct diagnosis was estimated.
      Suggestions about the way with which the parasite was introduced and maintained
      in Egypt were mentioned.

PMID- 12049251
TI  - The use of Ziehl-Neelsen stain, enzyme-linked immunosorbent assay and nested
      polymerase chain reaction in diagnosis of cryptosporidiosis in immuno-competent, 
      compromised patients.
AB  - In the present study, Cryptosporidium parvum was diagnosed in stool by Z-N stain,
      ELISA and PCR. The detected cases were 5.3%, 8.3% and 9.6% by the previous three
      methods, respectively. The sensitivity, specificity and accuracy of the different
      techniques were evaluated. The Z-N stain showed the lowest sensitivity and
      accuracy in relation to either ELISA or PCR. Moreover, the study revealed that
      the sensitivity, specificity and accuracy of ELISA detection of Cryptosporidium
      in relation to detection of DNA in stool by PCR were 84.2%, 96% and 88.8%,
      respectively. Consequently, PCR showed the best results. From a practical point
      of view, ELISA is recommended for wide spread use in diagnosis of
      cryptosporidiosis.

PMID- 12049252
TI  - A preliminary study on the relationship between Trichomonas vaginalis and
      cervical cancer in Egyptian women.
AB  - The relationship between Trichomonas vaginalis and cancer cervix was investigated
      by detection of T. vaginalis antibodies, in the sera of 48 invasive cervical
      cancer patients and 100 random age matched female control, using western
      immunoblot technique. It was found that antibodies to T. vaginalis were detected
      in sera of 18.75% (9/48) of cervical cancer patients compared with 5% (5/100) of
      controls. The increase was evident in age group, 40-49 years (21.05% vs 5%) and
      of those with squamous cell carcinoma (6/9) and mainly with grade II & III. All
      the reactive sera of invasive cancer patients reacted strongly with T. vaginalis
      surface antigen of about (109.9, 86.1, 56.2, 48.2 and 30 Kda). So, there may be
      an association between T. vaginalis and the risk of cervical cancer, as there was
      more than 3 fold increase in the prevalence of T. vaginalis antibodies in
      patients with invasive cervical cancer compared to age matched female controls.
      This study highlights the importance of clinically detection of T. vaginalis
      infection, which is one of the group of factors involved in the genesis and
      progression of cervical cancer. In addition, its treatment would aid in
      restricting the rising incidence of this dreaded disease.

PMID- 12049253
TI  - Effect of the amount of food given to the larvae on the life cycle of
      Parasarcophaga (Liopygia) ruficornis (F.).
AB  - The effect of food limitation upon developmental time, survival, weight,
      longevity and fecundity of adults was studied for Parasarcophaga (Liopygia)
      ruficornis (F.) at 25 degrees C, 60-65% RH and a 15:9 (L:D)h photoperiod, and
      offered food in 10 different weights (10-100 gm/100 larvae). The deveopmental
      time of larvae, and pupae decreased with the decrease in the amount of larval
      food for both sexes. Survive of the larval stage was not affected by decreasing
      the amount of larval food, while the pupal survival was significantly increased.
      The correlation between pupal weight and survival was significantly increased
      with the decreasing pupal weights. Pupal and adult weights decreased with the
      decrease in the amount of minced beef given as larval food for both sexes. There
      is no significant correlation between flies weights and longevity for both sexes.
      Females lived longer than males at three different weights. Fecundity of the
      medium-sized adult showed a higher average in number of larvae per female than
      the large or small-sized ones.

PMID- 12049254
TI  - Detection of E. histolytica, G. lamblia and Cryptosporidium copro-antigens in
      stool samples.
AB  - A double antibody sandwich ELISA technique, using a chromatography purified
      antisera against E. histolytica, G. lamblia and Cryptosporidium antigens, was
      applied to detect copro-antigens of the corrosponding parasites in 90 patients.
      All positive cases were diagnosed by parasitological examination and proved to
      have the infection solely. Beside the 90 positive cases, 40 age-matched controls
      were included in the study, of which 20 individuals were infected with other
      parasites but not Cryptosporidium, E. histolytica or G. lamblia (acted as an
      infected control group) and the other 20 individuals with no intestinal parasites
      (normal control group). The assay could detect 100% of those infected with both
      of G. lamblia and E. histolytica and 96.6% (29/30) of patients with
      Cryptosporidium infection. False positive reactions were detected in 3 cases
      using G. lamblia antisera (92.5%), 5 cases using E. histolytica antisera (87.5%)
      and 2 cases using Cryptosporidium antisera (95%). A direct increase in the mean
      antigen level was observed with the increasing intensity of infection in the 3
      parasites, so higher mean O.D. readings was observed in heavily infected cases
      than moderately infected cases than lighter intensity of infection. Only those in
      elder age group (> 20 years) infected with E. histolytica were found to have
      statistically higher O.D. readings of the antigen than middle age group (10-20
      years). On the other hand, no statistically significant difference was observed
      between different age groups and antigen level in cases with either G. lamblia or
      Cryptosporidium.

PMID- 12049255
TI  - Efficacy of praziquantel against Giardia lamblia in rats: parasitological,
      pathological and therapeutic study.
AB  - Rats were divided into two experimental groups received single or split doses of
      PZQ, and two control groups one infected untreated and the other normal healthy
      rats. The effect of infection on rat growth, on jejunal and duodenal architecture
      were studied histopathologically after H&E staining. The jejunal ultrastructure
      was examined by SEM and TEM. The effect of PZQ was evaluated using the same
      techniques. It was observed that infected as well as infected treated animals
      gained less weight than healthy control. Intensity of infection decreased
      gradually after treatment. Cure rate was 100% after split dose and 80% after a
      single dose. Altered villus height and cryptic depth were the characteristic
      changes in the architecture of the duodenum and jejunum, more pronounced in the
      latter. Split dose of PZQ revealed more improvement of the histopathological
      findings than a single dose. By SEM, circular imprints representing defects in
      the villi were observed in the jejunum. By TEM deformation of microvillar
      architecture was observed together with organellar changes in the RER and the
      mitochondria, after PZQ treatment.

PMID- 12049256
TI  - Oogram pattern, egg load and hatchability of eggs in mixed infection of
      Schistosoma mansoni and Schistosoma haematobium in hamster.
AB  - In mixed infection with Schistosoma mansoni and S. haematobium in hamsters,
      either simultaneously or after the full maturation of an initial infection with
      either schistosome species, a high level of acquired resistance was observed. The
      degree of immunity was magnified by the significant reduction in the number of
      eggs per gram tissue and hatchability of mature eggs. Some disturbance was also
      observed in the oogram pattern.

PMID- 12049257
TI  - A comparative study on the effect of praziquantel and triclabendazole on
      Vampirolepis nana in vitro.
AB  - V. nana was frequently associated with Schistosoma mansoni and Fasciola spp. This
      study was conducted to investigate and compare the effects of praziquantel and
      triclabendazole on V. nana worms, after in vitro exposure to 1 and 2 microg/ml of
      each of praziquantel or triclabendazole. All the worms were put under observation
      for 30 minutes. The worm mortality rates were recorded and the topographic
      tegumental changes were studied by scanning electron microscopy. The results
      demonstrated that praziquantel showed comparatively superior effect on adult V.
      nana worms than triclabendazole. The latter still revealed an anthelmintic
      effect.

PMID- 12049258
TI  - Experimental murine toxocariasis larval migration to liver, with a general
      discussion.
AB  - Street dogs were collected from Mansoura District and sacrificed. Toxocara canis
      worms were extracted from their intestines and females were dissected to collect
      the uteri ova. Maturation of the eggs developed larvae inside after a month. Male
      mice were orally infected with different inocula of these infective eggs (larvae
      eggs) and sacrificed at 1, 2, 4, 5, 9, 13 & 17 weeks post-infection (P.I.). Gross
      findings showed hepatomegaly, red spots on the surface, irregularity of the
      surface, yellowish spots and streaks. Histo-pathological examination revealed
      mild cellular infiltration in localized foci in group I (mice given 200 infective
      Toxocara eggs) but extensive in groups II and III (mice given 500 and 1000
      infective Toxocara eggs, respectively). Granulomas began to appear mice
      sacrificed 4 weeks P.I. in the three groups, but it was multiple in group III.
      Congestion of hepatocytes and sinusoids were detected, fatty degeneration was
      encountered in group III. Signs of regeneration were reported in group II & III.

PMID- 12049259
TI  - A new coccidian parasite (Apicomplexa: Eimeriidae) from the scimitar-horned oryx,
      Oryx dammah.
AB  - Oocysts of Eimeria oryxae sp. n. are described from the faeces of the scimitar
      horned oryx, Oryx dammah (Cretzschmar, 1826), from Zoo Garden, Riyadh City, Saudi
      Arabia. Sporulated oocysts were ellipsoid in shape measuring 20.9 x 17.1 (16.7
      24.2 x 15.5-20.2) microm, with smooth brownish-yellow double layered wall.
      Micropyle and ellipsoidal polar granules are present, but micropylar cap and
      oocyst residuum are absent. Sporocysts are ovoid, reaching 10.0 x 5.7 (9.2-11.0 x
      5.2-6.5) microm with Stieda body and sporocyst residuum. Sporozoites are
      elongated, each with large and small refractile body.

PMID- 12049261
TI  - Effectiveness of free radicals in hydatid cysts.
AB  - The lipid peroxidation (tbars) levels of fertile cyst liquids (0.84+/-0.14, 0.9+/
      0.12 micromol/L) for sheep liver and lung, respectively, were higher than
      infertile cyst liquids (0.29+/-0.07, 0.20+/-0.06 micromol/L) for sheep liver and
      lung (p < 0.05). There were no significant differences between fertile cyst
      membranes (0.71+/-0.12, 0.74+/-0.27 nmol/mg wet tissue protein for liver and
      lung, respectively) and infertile cyst membranes (0.37+/-0.11, 0.39+/-0.15
      nmol/mg wet tissue protein) in terms of tbars levels (p > 0.05). The lipid
      peroxidation levels determined for protoscoleces (1.99+/-0.45, 2.07+/-0.20
      nmol/mg wet tissue protein for sheep liver and lung, respectively) were
      significantly higher than those of fertile cyst membranes (p < 0.05) and than
      those of infertile cyst membranes (p < 0.01). NO levels of cattle fertile hydatid
      liquids (liver nitrite; 2.07+/-0.73 nmol/L, liver nitrate; 4.01+/-1.15
      micromol/L, lung nitrite; 2.44+/-0.70 umol/L, lung nitrate; 0.87+/-0.30
      micromol/L) were significantly higher compared to cattle infertile hydatid
      liquids (liver nitrite; 0.66+/-0.29 micromol/L, liver nitrate; 1.10+/-0.41
      umol/L, lung nitrite; 0.55+/-0.15 micromol/L, lung nitrate; 0.54+/-0.16
      micromol/L) (p < 0.05).

PMID- 12049260
TI  - Protein G ELISA for detection of antibodies against Toxoplasma SAG1 in
      dromedaries.
AB  - ELISA was used for detection of antibodies against the immunodominant surface
      antigen 1 (SAG1, synonymous P30) of Toxoplasma gondii, and peroxidase-conjugated
      protein G was used instead of commercially unavailable enzyme-conjugated anti
      dromedary antibody. A latex agglutination test was employed to select 20
      seronegative control animals, and peroxidase-conjugated protein A was used for
      comparison with protein G. The overall seroprevalence rate was 31.4%; males had
      to some extent higher seropositive rate than females (P = 0.077). Seropositive
      camels sampled in winter had significantly higher-antibody levels than those
      sampled in summer (P < 0.01). ELISA values using protein G and protein A
      conjugates were significantly correlated (Spearman's rho = 0.797; n = 185; P <
      0.001). The results were discussed.

PMID- 12049262
TI  - Effect of Allium cepa and Allium sativum feeding on glucose, glycogen, protein
      bands profile and phenol oxidase activity in Biomphalaria alexandrina.
AB  - Feeding B. alexandrina on onion and garlic powder (Allium cepa and Allium
      sativum) separately exert some biological and biochemical changes. The effect of
      the two plants on glucose and glycogen which are the energy fuel of the snails,
      and on phenol oxidase (PO) activity after 1, 2, 3 and 7 days were studied.
      Different protein bands were separated from the control and treated snails
      haemolymph after 24 hours and one week by using SDS-electrophoresis. The study
      revealed that glucose and glycogen were decreased significantly after feeding on
      onion and garlic. Also phenol oxidase (PO) activity was highly significantly
      decreased after 2 and 7 days of feeding on garlic while feeding on onion
      decreased the activity of the enzyme at all periods. Data obtained from SDS
      electrophoresis showed variations in the different protein bands reflect the
      enzymatic change in the snails' tissue. So, the snails' fecundity may be reduced
      and in turn disturb the life cycle of schistosome parasite.

PMID- 12049264
TI  - Effect of sublethal concentrations of Atriplex halimus (Chenopediaceae) on
      Biomphalaria alexandrina, the snail-vector of Schistosoma mansoni in Egypt.
AB  - Effect of sublethal concentrations of Atriplex halimus on the mortality rate,
      longevity, egg production of Biomphalaria alexandrina and hatchability of their
      eggs were studied. The sublethal concentrations of Atriplex caused reduction in
      survival rates, longevity and egg production of B. alexandrina. Hatchability of
      snail eggs exposed to tested plant was decreased by increasing its
      concentrations.

PMID- 12049263
TI  - Molluscicidal activities of certain pesticide and their mixtures against
      Biomphalaria alexandrina.
AB  - The niclosamide and uccmaluscide proved to be the most effective compounds,
      followed by copper sulphate. The second category of efficiency includes the
      anilofos, isoprothiolane and fluazifop-P-butyl. Moreover, Butachlor herbicide was
      the least potent compound. In general, the specific molluscicides showed more
      efficiency than the conventional tested herbicides and fungicides on treated
      snails. Pre-exposure to 1/10 LC50 of anilofos, butachlor and isoprothiolane
      showed synergistic effects to uccmaluscide. However, the same treatment with 1/10
      LC50 of fluazifop-P-butyl, isoprothiolane and butachlor gave additive effect to
      copper sulphate and niclosamide on treated snails. Data indicated that when
      butachlor, anilofos, fluazifop-P-butyl or isoprothiolane added to copper sulphate
      at the ratios of 10:40, 20:30 of LC50 as well as anilofos when added to copper
      sulphate at 30:20 showed synergism in activity against snails. On the contrary,
      the tested mixtures with niclosamide resulted in antagonistic action, while
      pesticide uccmaluscide mixtures showed synergistic effect, except isoprothiolane
      uccmaluscide mixture at ratio 40:10 of LC50 showed additive effect on snails.
      Determination of niclosamide by gas chromatography, indicated that niclosamide
      showed relatively slower degradation either in the case of niclosamide or it's
      mixture with butachlor. Meanwhile, it's mixture with anilofos or fluazifop-p
      butyl or isoprothiolane showed rapid degradation.

PMID- 12049265
TI  - The molluscicidal efficacy of three products against Biomphalaria alexandrina and
      Lymnaea natalensis.
AB  - Toxicity of three local formulated products, Sol E.C (mineral oil), Sisi-6
      (surfactant) and Castor bean oil E.C (plant oil) were tested against Biomphalaria
      alexandrina and Lymnaea natalensis, in two water sources. Results indicated that
      in dechlorinated water after 24 hr exposure, castor bean oil was the most toxic
      product against the snails, followed by Sisi-6 and sol (E.C) with LC90 of 250 ppm
      and 8 ppm against B. alexandrina and L. natalensis, respectively. When Nile water
      was used after 6 hr. exposure, a high concentration of castor bean oil (4 LC90)
      did not achieve 100% mortality of the snails. A 100% mortality was achieved by 2
      LC90 of Sisi-6 with Nile water. On the other hand, caster bean oil was more fatal
      to eggs of the snails (LC90=660 ppm) than the other two products. In general, L.
      natalensis was more susceptible to the experimental products than B. alexandrina.

PMID- 12049266
TI  - A review on fascioliasis in Egypt.
AB  - Fascioliasis, caused by Fasciola species, is a disease of herbivorous animals. It
      has a worldwide distribution in a large variety of grass-grazing animals as
      sheep, goats, cattle, buffaloes, horses and rabbits. In Egypt, donkeys and camels
      as well, are hosts for F. gigantica. Fascioliasis may occasionally affect man.
      Human infection causes serious hepatic pathological sequences that add to the
      already known threats to the liver of the Egyptian population. Two clinical
      stages are recognized in human fascioliasis. An acute stage coincides with the
      larval migration and worm maturation in the hepatic tissue, and a chronic stage
      coincides with the persistence of Fasciola worms in the bile ducts. Human
      infection with fascioliasis was very sporadic until the last three decades where
      clinical cases and outbreaks were reported. The estimated the number of people
      currently having fascioliasis to be 360,000 in Bolivia, 20,000 in Ecuador,
      830,000 in Egypt, 10,000 in Islamic Republic of Iran, 742,000 in Peru, and 37,000
      in Yemen. The total estimated number of people infected is 2.4 million in 61
      countries and that the number at risk is more than 180 million throughout the
      world. Human fascioliasis has to be differentially diagnosed from some diseases
      as acute hepatitis, infection with other liver flukes as schistosomiasis,
      visceral toxocariasis, biliary tract diseases and hepatic amoebiasis. The
      parasitological diagnosis is based on identification of eggs in stool, duodenal
      contents or bile, also by the recovery of adult worm during surgical exploration,
      after treatment or at autopsy. However, the eggs may be present in very small
      number at irregular intervals, hence difficult to be found. Besides, the eggs may
      be transiently present in stool after ingestion of raw or undercooked liver from
      infected animals. The direct methods of diagnosing the egg are usually
      unsatisfactory. The symptoms may be present for several weeks before eggs are
      recovered in stool. Thus, the serologic tests are the alternative method of
      confirming early and extrabiliary human fascioliasis. However, cross-reactions
      with other helminthic antigen may confuse the interpretation of the results.

PMID- 12049267
TI  - Incidence of cryptosporidiosis in immunodeficient cancer patients in Egypt.
AB  - A coproprotozoal study was carried out on 63 patients suffering from malignancy.
      The majority had cancer of haemopoietic system. All patients were under
      chemotherapy and included: Group A (33 children) and Group B (30 adults) of whom
      20 immunocompetent diarrhoeic patients of matched age and sex were considered as
      controls. Stool samples were examined by merthiolate iodine-formaldehyde
      concentration technique (MIF). Modified Zeihl-Neelsen (ZN) stain was performed
      for Cryptosporidium oocysts. Detection of Cryptosporidium coproantigen by enzyme
      linked immunoassay test (Ridascreen test), was used. Immunoglobulins (IgG, IgM,
      IgE & IgA), C3, C4 and CD4:CD8 ratio, were measured. According to their levels 25
      out of 63 patients had both humoral and cellular immunodeficiency. The incidence
      of Cryptosporidium in cancer patients was 23.8%, while it was 37.7% and 91% in
      children and adults immunodeficient patients, respectively. ZN stain was able in
      diagnosed Cryptosporidium in 13 out of 35 immunodeficient cases while ELISA
      detected only 11 cases. Cryptosporidium infection in immunodeficient cancer
      patients had significantly more frequent and prolonged duration of diarrhoea than
      in negative ones.

PMID- 12049268
TI  - A case report of human dirofilariasis in Egypt.

PMID- 12049270
TI  - Biological and morphological changes in worms in mixed infection of Schistosoma
      mansoni and S. haematobium in hamsters.
AB  - Hamsters infected with Schistosoma mansoni and S. haematobium either
      simultaneously or after maturation of an initial infection with either
      schistosome species were examined to estimate the biological and morphological
      changes under mixed infection conditions. The results indicate a high level of
      acquired resistance. The degree of immunity was evidenced by the significant
      reduction in the worm load as well as in the size of mature worms. Some
      disturbance was observed in the worm distribution. The results are important for
      epidemiological and immunological uses, as well as in development of a vaccine
      from one species that might be effective against both species.

PMID- 12049269
TI  - Fascioliasis among live and slaugthered animals in nine centers of Dakahlia
      Governorate.
AB  - Fascioliasis is an important zoonotic disease. Infected animals are the main
      source for human fascioliasis. Consequently, this work clarifies the status of
      animal fascioliasis in Dakahlia centers based on parasitological examination of
      cows, buffaloes, sheep and goats. The overall rates of infection were 12.31%,
      9.73%, 17.84% and 5.40% respectively. The mean eggs per gram stool were 22, 13.6,
      148.3 and 8.6 for cows, buffaloes, sheep and goats. The mean numbers of Fasciola
      worms/liver/animal were 69.1, 62.7 and 208.1 for cows, buffaloes and sheep
      respectively. The highly infected sheep was in Manzalla (23.07%), the lowest was
      in Mataria (6.35%). The highly infected cows was in Manzalla (20.9%), the lowest
      was in Sherbeen (9.43%). The highly infected buffaloes was in Manzalla (19.29%),
      the lowest was in Mit Ghamr (4.93%). The relatively highly infected goats was in
      Manzalla (12.5%) and the lowest was zero in Mit Ghamr. So, sheep are the main
      reservoir host for environmental pollution and human fascioliasis. On the other
      hand, the overall partial condemnation of liver was 3.81% (1997), 3.24% (1998),
      2.66% (1999) and 2.64% (2000). Regarding the type of animal, it was 6.38% in
      cows, 1.74% in buffaloes and 1.0% in sheep. It seems that sheep are most
      susceptible to fascioliasis treatment, followed by buffaloes and lastly cows. The
      epidemiological role of these farm animals as source for fascioliasis infection
      to animals and man was discussed.

PMID- 12049271
TI  - Urinary antigen detection for diagnosis of hydatid disease.
AB  - Hydatid antigen was demonstrated for the first time in urine of patients with
      hydatidosis by coagglutination test (Co-A). Urinary antigen was detected in all
      Co-A positive serum corresponding samples of surgically confirmed hydatid
      disease. The sensitivity and specificity were 100% in urine compared with the
      corresponding serum samples. These results clarified that the use of Co-A test
      for detection of hydatid antigen in urine is an easy, simple, rapid, non-invasive
      and efficient method for diagnosis of hydatidosis.

PMID- 12049272
TI  - Evaluation of two serological tests in diagnosis of human cases of biliary and
      ectopic fascioliasis.
AB  - In the present study, sera were examined using Fasciola-IHA, F-ELISA and
      Schistosoma-IHA. The sero-positive schistosomal patients were subjected to rectal
      snip, while the sero-positive fascioliasis ones were examined radiologically by
      plain chest X-ray and abdominal ultrasonography. Both F-IHA and F-ELISA gave 100%
      sensitivity. The specificity of both testes were 90.4% and 100% respectively.
      With the S-IHA, the parasitologically proven schistosomal mansoni patients gave
      95% positivity, while the proven fascioliasis patients gave false positive (8%)
      with this S-IHA. The radiological findings of the fascioliasis patients confirmed
      ectopic pleuro-pulmonary infection in five patients. Ascitis was detected in one
      patient, the pleural effusion and ascitic fluids showed high eosinophils.
      However, Fasciola eggs were detected in three patients only. Two patients showed
      hepatic nodules, and another two had hepatic cystic lesions. Three patients had
      immature Fasciola worms in gall bladder. For diagnosis of human fascioliasis,
      serological and radiological means should be done side by side with the stool
      examination. This is particularly true in chronic cases and in schistosomiasis
      mansoni endemic areas.

PMID- 12049273
TI  - Mosquito species and their densities in some Egyptian governorates.
AB  - The present work studied the mosquito's identification, distribution and
      densities in fourteen Egyptian Governorates. The abundance and distribution of
      mosquito species monitored by three phases. The first was carried out in 1999 in
      five governorates, Qalyobia, Menoufia, Behaira, Fayium and Assuit. The second was
      in the year 2000 in Kafr El Sheikh, Giza, Sharkia, Menia and Aswan. The third was
      in the year 2001 in Kena, El Wady El Gadeed, Dakahlia and South Sinai. Culex
      species were the commonest mainly C. pipiens, C. antennatus and C. univittatus.
      C. thelerei was found only in El Kharga Oasis. Culiseta sp. was found in
      Qalyobia, Menofia, Behaira, Fayium, El Wady El Gadeed, Dakahlia and South Sinai
      and as larvae in Kafr El Sheikh, Giza, and Menia. Aedes detritus was found in
      Assiut, Fayium, Giza, Aswan, El Wady El Gadeed and South Sinai. Ae. caspius was
      found in Assiut and Aswan and as larvae in Kena and El Wady El Gadeed. Anopheles
      pharoensis was found in Behaira and Fayium, while A. algeriensis in Aswan. A.
      multicolor and A. sergentii were found in Fayium, Aswan and El Wady El Gadeed;
      but in Kena A. sergentii was found as larvae and A. multicolor as adults.

PMID- 12049274
TI  - Field studies on the susceptibility of housefly to certain insecticides in nine
      Egyptian governorates.
AB  - Standard WHO test methods were used to determine the susceptibility of field
      population of housefly to four organophosphorous and two pyrethroid insecticides.
      Field population flies collected from nine governorates, Giza, Faiyoum, Suez,
      Behaira, Menoufia, Sharkia, Kafr El-Sheikh, Assiut and Aswan. The results
      indicated that, all tested insecticides were very effective on flies collected,
      from Sharkia, Kafr El-Sheikh and Aswan, but there was an evidence of increased
      vigor tolerance among those collected from Kafr El-Sheikh for bioresmethrin and
      tolerance for diazinon in Aswan. In Assiut, flies exhibited high sensitivity to
      diazinon, deltamethrin and bromophos while malathion was the least effective
      adulticide. Resistance to malathion, diazinon, fenthion and bioresmethrin was
      noticed in varying degrees at all governorates. The highest average resistance
      ratio was recorded for malathion in Behaira (55.3 folds) and in Suez (26 folds).
      Resistance was also more pronounced in Menoulia for diazinon (23.3 folds). As for
      bioresmethrin an apparent increase in the resistance ratio was detected in Suez
      (25 folds). In Giza. houseflies were resistant to fenthion (14.5 folds).
      Regarding the difference between the six insecticides used, deltamethrin was the
      most potent insecticide in all governorates.

PMID- 12049275
TI  - Control of Ctenocephalides felis on dogs and cats using the insect growth
      regulator (or chitin synthesis inhibitor) lufenuron Program, in Egypt.
AB  - Lufenuron, the chitin synthesis inhibitor (Program, Novartis-Switzerland) was
      given orally at doses of 10-mg/kg b/w to dogs and 30-mg/kg b/w to cats every four
      weeks (monthly) for the treatment of experimental flea infestations. Three to
      four weeks after the last infestation, Lufenuron had effectively controlled the
      Ct. felis infestation of dogs and cats as the drug prevented the development of
      the offspring of adult female fleas feeding on animals. Flea populations were
      absent or very low and remained so until the end of the study, 91 days after the
      first treatment.

PMID- 12049276
TI  - Face recognition by hand.
AB  - We investigated participants' ability to identify and represent faces by hand. In
      Experiment 1, participants proved surprisingly capable of identifying unfamiliar
      live human faces using only their sense of touch. To evaluate the contribution of
      geometric and material information more directly, we biased participants toward
      encoding faces more in terms of geometric than material properties, by varying
      the exploration condition. When participants explored the faces both visually and
      tactually, identification accuracy did not improve relative to touch alone. When
      participants explored masks of the faces, thereby eliminating material cues,
      matching accuracy declined substantially relative to tactual identification of
      live faces. In Experiment 2, we explored intersensory transfer of face
      information between vision and touch. The findings are discussed in terms of
      their relevance to haptic object processing and to the face-processing literature
      in general.

PMID- 12049277
TI  - The Muller-Lyer illusion in touch and vision: implications for multisensory
      processes.
AB  - In six experiments, we used the Muller-Lyer illusion to investigate factors in
      the integration of touch, movement, and spatial cues in haptic shape perception,
      and in the similarity with the visual illusion. Latencies provided evidence
      against the hypothesis that scanning times explain the haptic illusion.
      Distinctive fin effects supported the hypothesis that cue distinctiveness
      contributes to the illusion, but showed also that it depends on modality-specific
      conditions, and is not the main factor. Allocentric cues from scanning an
      external frame (EF) did not reduce the haptic illusion. Scanning elicited
      downward movements and more negative errors for horizontal convergent figures and
      more positive errors for vertical divergent figures, suggesting a modality
      specific movement effect. But the Muller-Lyer illusion was highly significant for
      both vertical and horizontal figures. By contrast, instructions to use body
      centered reference and to ignore the fins reduced the haptic illusion for
      vertical figures in touch from 12.60% to 1.7%. In vision, without explicit
      egocentric reference, instructions to ignore fins did not reduce the illusion to
      near floor level, though external cues were present. But the visual illusion was
      reduced to the same level as in touch with instructions that included the use of
      body-centered cues. The new evidence shows that the same instructions reduced the
      Muller-Lyer illusion almost to zero in both vision and touch. It suggests that
      the similarity of the illusions is not fortuitous. The results on touch supported
      the hypothesis that body-centered spatial reference is involved in integrating
      inputs from touch and movement for accurate haptic shape perception. The finding
      that explicit egocentric reference had the same effect on vision suggests that it
      may be a common factor in the integration of disparate inputs from multisensory
      sources.

PMID- 12049278
TI  - Illusory 3-D rotation induced by dynamic image shading.
AB  - Observers' perceptions of the three-dimensional structure of smoothly curved
      surfaces defined by patterns of image shading were investigated under varying
      conditions of illumination. In five experiments, observers judged the global
      orientation and the motion of the simulated surfaces from both static and dynamic
      patterns of image shading. We found that perceptual performance was more accurate
      with static than with dynamic displays. Dynamic displays evoked systematic biases
      in perceptual performance when the surface and the illumination source were
      simulated as rotating in opposite directions. In these conditions, the surface
      was incorrectly perceived as rotating in the same direction as the illumination
      source. Conversely, the orientation of the simulated surfaces was perceived
      correctly when the frames making up the apparent-motion sequences of the dynamic
      displays were presented as static images. In Experiment 6, moreover, the results
      obtained with the computer-generated displays were replicated with solid objects.

PMID- 12049279
TI  - Pappus in optical space.
AB  - Optical space differs from physical space. The structure of optical space has
      generally been assumed to be metrical. In contradistinction, we do not assume any
      metric, but only incidence relations (i.e., we assume that optical points and
      lines exist and that two points define a unique line, and two lines a unique
      point). (The incidence relations have generally been assumed implicitly by
      earlier authors.) The condition that makes such an incidence structure into a
      projective space is the Pappus condition. The Pappus condition describes a
      projective relation between three collinear triples of points, whose validity can
      -in principle--be verified empirically. The Pappus condition is a necessary
      condition for optical space to be a homogeneous space (Lobatchevski hyperbolic or
      Riemann elliptic space) as assumed by, for example, the well-known Luneburg
      theory. We test the Pappus condition in a full-cue situation (open field, broad
      daylight, distances of up to 20 m, visual fields of up to 160 degrees diameter).
      We found that although optical space is definitely not veridical, even under full
      cue conditions, violations of the Pappus condition are the exception. Apparently
      optical space is not totally different from a homogeneous space, although it is
      in no way close to Euclidean.

PMID- 12049280
TI  - Visual perception of collinearity.
AB  - In a metrical space, there exists an intimate relation between collinearity and
      parallelity. In particular, in a Riemannian space collinearity is just a special
      case of parallelity. Is this true for visual space as well? We investigated the
      visual perception of collinearity by having subjects align two bars in the
      horizontal plane at eye height. The distances of the bars from the subject and
      the angles at which they were placed were varied. We found deviations of up to 22
      degrees. The deviations of the left and right bars could be split into two
      independent components: namely, the sum and the difference of the deviations of
      the left and right bars. We found that the former depended only on the ratio
      between the distances of each bar from the subject, whereas the latter was
      largely independent of the positions of the bars. The difference in deviations
      corresponded to the deviation from parallelity. Compared with the results in the
      parallelity task (Cuijpers, Kappers, & Koenderink, 2000b), the deviations from
      parallel were much smaller. As a consequence, the results of the two experiments
      cannot be described by the same Riemannian geometry. This indicates that the
      intrinsic geometry of visual space differs across tasks. This is conceivable if
      the intrinsic geometry of visual space is operationally defined.

PMID- 12049281
TI  - Relative distance cues contribute to scaling depth from motion parallax.
AB  - The visual system scales motion parallax signals with information about absolute
      distance (M. E. Ono, Rivest, & H. Ono, 1986). The present study was designed to
      determine whether relative distance cues, which intrinsically provide information
      about relative distance, contribute to this scaling. In two experiments, two test
      stimuli, containing an equal extent of motion parallax, were presented
      simultaneously at a fixed viewing distance. The relative distance cues of dynamic
      occlusion and motion parallax in the areas surrounding the test stimuli
      (background motion parallax) and/or relative size were manipulated. The observers
      reported which of the two parallactic test stimuli appeared to have greater
      depth, and which appeared to be more distant. The results showed that the test
      stimulus specified, by the relative distance cues, as being more distant was
      perceived as having more depth and as being more distant. This indicates that
      relative distance cues contribute to scaling depth from motion parallax by
      modifying the information about the absolute distance of objects.

PMID- 12049282
TI  - Walking, looking to the side, and taking curved paths.
AB  - In two experiments, viewers judged heading from displays simulating locomotion
      through tree-filled environments, with gaze off to the side. They marked their
      heading with a mouse-controlled probe at three different depths. When simulated
      eye or head rotation generally exceeded 0.5 deg/sec, there was reliable curvature
      in perceived paths toward the fixated object. This curvature, however, was slight
      even with rotation rates as great as 2.6 deg/sec. Best-fit paths to circular arcs
      had radii of 1.8 km or greater. In a third experiment, pedestrians walked with
      matched gaze to the side. Measured curvature in the direction of gaze
      corresponded to a circular radius of about 1.3 km. Thus, at minimum, vision
      scientists need not worry about perceived path curvature in this situation; real
      path curvatures are about the same. However, at present, we can make no claim
      that the same mechanisms necessarily govern the two results.

PMID- 12049283
TI  - Transfer of learning across durations and ears in auditory frequency
      discrimination.
AB  - Frequency-discrimination thresholds (FDTs) for 1-kHz tone pips with durations of
      40, 100, and 200 msec were measured in the left and right ears of 10 normal
      hearing listeners, before and after six 2-h frequency-discrimination training
      sessions involving, exclusively, the 200-msec duration and the right ear. In the
      trained ear, highly significant improvements in FDTs were observed at all
      durations. Further inspection of the data suggested complete generalization
      between 200 and 100 msec, but not at 40 msec. Posttraining FDTs were not found to
      differ between the two ears for the two untrained durations, but proved
      significantly smaller in the right (trained) than in the left (untrained) ear at
      the trained (200-msec) duration only. A control experiment involving 10
      additional subjects allowed us to establish the absence of intrinsic differences
      in pretraining FDTs between the right and left ears. Overall, these findings
      indicate that frequency-discrimination learning generalizes widely across
      stimulus durations and across ears, but that part of the improvement is specific
      to the range of durations and to the ear used in training.

PMID- 12049284
TI  - Pitch strength and Stevens's power law.
AB  - Recent studies have suggested that the saliency or the strength of pitch of
      complex sounds can be accounted for on the basis of the temporal properties in
      the stimulus waveform as measured by the height of the first peak in the waveform
      autocorrelation function. We used a scaling procedure to measure the pitch
      strength from 15 listeners for four different pitches of complex sounds in which
      the height of the first peak in the autocorrelation function systematically
      varied. Pitch strength judgments were evaluated in terms of a modification of
      Stevens's power law in which temporal information was used from both the waveform
      fine structure and the envelope. Best fits of this modified power law to the
      judged pitch strengths indicate that the exponent in Stevens's power law is
      greater than 1. The results suggest that pitch strength is primarily determined
      by the waveform fine structure, but the stimulus envelope can also contribute to
      the pitch strength.

PMID- 12049285
TI  - Perception and production of rise-fall intonation in American English.
AB  - At the segmental level, the rate of speaking affects the degree of physical
      undershoot of articulatory targets and the resulting perception. Little is known
      regarding evidence of these effects at the suprasegmental level, particularly in
      intonation. In this study, the effect of rate of speaking on fundamental
      frequency and on perceptual judgments of peak pitch in a rise-fall intonation
      pattern was investigated. First, speakers produced rise-fall intonations in
      sentence contexts at slow, normal, and fast speaking rates. Peak fundamental
      frequencies (F0) of the slow productions were significantly lower than those of
      the normal or fast productions. The mean normal rate production of the word Miami
      was used as a model for the target word in a series of subsequent perceptual
      experiments. Altering the duration of the target word to represent slow, normal,
      and fast rates of speaking did not affect listener judgment of peak pitch.
      Finally, the pitch of the target word was measured in a sentence context. No
      differences between peak pitch in isolation or in sentence context were found. It
      was concluded that the production and perception of this form of intonation was
      not subject to the effects of rate that are seen at the segmental level.

PMID- 12049286
TI  - Size scaling: retinal or environmental frame of reference?
AB  - Previous studies have reported that when subjects are presented with two forms in
      a same-different task, their reaction times increase with the size ratio. This
      suggests a "mental scaling" transformation analogous to the "mental rotation"
      used to compensate for differently oriented forms in similar tasks. However,
      since the stimuli were presented in isolation, retinal and environmental size
      ratios were confounded. The present study varied both retinal and environmental
      size ratios in a same-different simultaneous matching task. In one experiment,
      random forms were placed at different distances along a textured hallway. A
      second experiment varied the monocular size information: In one condition the
      forms were displayed in a textured hallway; a second condition added cast
      shadows; and a third condition displayed the forms against a frontal wall of
      indeterminate distance. The results suggest that environmental size is determined
      prior to mental scaling and form matching.

PMID- 12049287
TI  - Context effects in visual length perception: role of ocular, retinal, and spatial
      location.
AB  - In three experiments, we examined the transfer of orientation-contingent context
      effects between the eyes and across portions of the retina with or without
      variation in external spatial location. Previous research had shown that vertical
      lines are judged long, relative to horizontal lines, when the stimulus set
      comprises relatively long horizontals and short verticals (Contextual Condition
      B), as compared with the reverse when the stimulus set comprises relatively short
      horizontals and long verticals (Contextual Condition A). Consequently, the
      contextual set of stimuli influences the magnitude of the horizontal-vertical
      illusion (HVI), decreasing its size under Contextual Condition A and increasing
      its size under Contextual Condition B. Experiment 1 showed that exposing one eye
      to different stimulus contexts modulated the size of the HVI at the exposed eye
      but had little or no effect at the other eye. Experiments 2 and 3 showed that the
      effect of the contextual sets generalized poorly across adjacent portions of the
      retina but transferred almost perfectly across different locations in external
      space when retinal location was constant. Thus, orientation-contingent context
      effects in visual length perception appear to be specific to the eye and to the
      region of the retina stimulated, suggesting that these effects reflect relatively
      early and local changes in sensitivity, rather than relatively late and general
      shifts in response criteria.

PMID- 12049288
TI  - Cross-dimensional interference and cross-trial inhibition.
AB  - In two experiments, we examined whether one source of cross-dimensional
      interference in visual search involves cross-trial position priming. In
      Experiment 1, we demonstrated cross-dimensional interference in search for an
      orientation-defined target: Search for a left-tilted target among right-tilted
      non-targets was disrupted by the presence of a singleton color distractor. In all
      conditions, search was facilitated when a target was presented at the same
      position as a target in the previous trial (positive position priming). In
      addition, there were negative effects of position priming on orientation targets
      that fell on the same side as singleton distractors on the previous trial. In
      Experiment 2, to examine the impact of negative position priming on cross
      dimensional interference, trials with and without singleton distractors were
      presented in a single trial block. The chance of a singleton distractor's being
      present on a preceding trial was then equated across displays when the distractor
      was and when it was not subsequently present. Cross-dimensional interference was
      eliminated under this mixed presentation condition, suggesting that the cost of
      cross-dimensional interference was not determined by the stimulus-driven factors
      in the current trial, at least when a limited number of target and distractor
      locations was used. We conclude that top-down selection is possible during visual
      search, and this leads to inhibition of the location of salient distractors. The
      cost of this is slowed detection of targets at inhibited locations on subsequent
      trials.

PMID- 12049289
TI  - A correction and a comment on Craig and Lyle (2001).
AB  - In a recent paper, Craig and Lyle (2001) measured tactile spatial acuity on the
      palm and compared these results with the results from similar measures on the
      fingertip. The changes in sensitivity between the two sites appeared to be
      consistent with estimates of the relative density of innervation between the two
      sites. Rather than compare their results with changes in the density of
      innervation, Craig and Lyle should have compared them with changes in the spacing
      between receptors. On this basis, psychophysical performance is much poorer on
      the palm than one would predict on the basis of the spacing between receptors.
      Some possible reasons are offered for the difference between the psychophysical
      results and the predictions based on receptor spacing.

PMID- 12049290
TI  - A study of the mechanisms involved in relaxation induced by 17-beta-estradiol in
      the isolated rabbit aorta.
AB  - We used the isolated rabbit aorta to examine the mechanisms that mediate the
      known vasodilatation induced by 17-beta-estradiol. Our results suggest that
      nitric oxide (NO), the inhibition of Ca2+ release from intracellular stores
      through the IP3 pathway and Ca2+ influx through potential-dependent calcium
      channels (PDCs) seem to be involved. Prostaglandins and adrenergic beta receptors
      do not influx, intracellular Ca2+ release, NO, cyclic guanine monophosphate
      (cGMP), prostaglandins and adrenergic beta receptors.

PMID- 12049291
TI  - Oxygen saturation in healthy newborn infants immediately after birth measured by
      pulse oximetry.
AB  - Pre- and postductal arterial oxygen saturation (SpO2) rates were measured in 50
      healthy vaginally delivered newborn infants to establish reference values of SpO2
      rates immediately after birth. We compared the SpO2 values in the pre- and
      postductal areas and assessed the influence of oxitocin and analgetics applied
      during delivery. Fifty neonates were examined by the 2nd minute (min) of life
      using Nellcor N-3000 pulse oximeters on the right hand and foot. Measurements
      were carried out until a SpO2 of 95% was achieved. Heart rates were registered
      simultaneously. Two min after birth the mean preductal SpO2 was 73% (44-95%) and
      67% (34-93%) in the postductal region. SpO2 rates of > 95% were reached after 12
      min (2-55 min) preductally and after 14 min (3-55 min) postductally. Our results
      demonstrate that it takes 12-14 min for healthy neonates to reach an oxygen
      saturation of 95% prerespectively postductal, in some cases even 55 min. All
      neonates were in good clinical condition and didn't require any supplemental
      oxygen. Additionally, we were able to show that epidural anaesthesia (PDA) during
      delivery increases the heart rate of the newborn infant.

PMID- 12049292
TI  - Influences of stroma-derived growth factors on the cytokine expression pattern of
      human breast cancer cell lines.
AB  - Tumor growth and local invasion are greatly dependent on the malignant potential
      of a tumor cell, but are also significantly modulated by a variety of local
      factors. These factors comprise cytokines, growth factors and extracellular
      matrix proteins (ECM), which act through a complex system of auto-, para- and
      juxtacrine interactions. Some factors are produced by the malignant cell itself,
      others are expressed by adjacent tumor stroma, migrated inflammatory cells, or
      resident macrophages. We have investigated the influences of cytokines and growth
      factors known to be expressed by tumor stroma on the cytokine expression pattern
      of three human breast cancer cell lines of different malignant potential. MCF-7,
      T47D and MDA-MB-231 were incubated with human recombinant TNF-alpha, IGF-I, IGF
      II, bFGF, HGF or G-CSF and the pattern of tumor-cell-derived TGF-beta1, bFGF, IL
      1alpha and VEGF was analyzed. Among the three cell lines used we observed a
      heterogenous response to stromal cytokines by measuring above mentioned factors
      in the cell culture's supernatants, but no clear correlation between malignant
      potential and cytokine expression pattern seemed obvious. We hypothesize that
      local growth factors may have a significant modulatory effect on malignant
      behavior in vivo. We conclude that this effect might depend on individual
      responses and on the differentiation state of tumor cells.

PMID- 12049293
TI  - Evaluation of acrosome reaction and viability of human sperm with two fluorescent
      dyes.
AB  - OBJECTIVE: To evaluate the usefulness of the Hoechst 33258/FITC-Pisum sativum
      agglutinin (FITC-PSA) staining for simultaneous assessment of viability and
      acrosome reaction rate (%AR) of human sperm. MATERIAL AND METHODS: Fresh sperm
      was collected 13 fertile donors provided fresh semen. We used motile sperm
      selected by the "swim-up" procedure using modified HTF. Hoechst 33258 was added
      and co-incubated with sperm for 10 min. Samples were washed free of unbound stain
      and the sperm were mounted as smears on glass slides. After drying, sperms were
      incubated with FITC-PSA for 30 min. Sperm were examined by fluorescence
      microscopy. Also, FITC-Concanavalin A (FITC-ConA) staining and vital staining
      with yellowish eosin were performed simultaneously. The correlation of viability
      and %AR were analyzed. RESULTS: Four different staining patterns were observed
      and clearly distinguished as follows: a) Viable acrosome-reacted sperm, b) Viable
      acrosome-intact sperm, c) dead acrosome-reacted sperm, d) dead acrosome-intact
      sperm. There was significant correlation between the results obtained by Hoechst
      33258 and vital staining methods in viability of human sperm (r = 0.927, P <
      0.001). There was significant correlation between the two methods (FITC-PSA and
      FITC-ConA) in %AR of human sperm (r = 0.92, P < 0.001). CONCLUSION: Viability and
      acrosome status of a human sperm can be easily assessed simultaneously by Hoechst
      33258/FITC-PSA staining method. This combination method is considered useful to
      evaluate sperm function.

PMID- 12049294
TI  - Bilateral torsion of the testicles in a newborn.
AB  - We describe a case of bilateral torsion of the testes in a full term neonate.

PMID- 12049295
TI  - Uterine leiomyosarcoma metastatic to the brain stem.
AB  - A patient with a history of an uterine leiomyosarcoma presented with diplopia,
      gait disturbances, and hypesthesia of the right face. MRI of the head showed a
      lesion located in the pons and causing obstructive hydrocephalus. Open biopsy
      revealed a metastatic tumor with histological features of leiomyosarcoma. Despite
      whole-brain irradiation, the patient died due to respiratory arrest. This case
      illustrates that brain stem metastasis may occur as a rare complication in
      uterine leiomyosarcoma.

PMID- 12049296
TI  - A favorable outcome of pregnancies in women with primary and secondary recurrent
      pregnancy loss associated with antiphospholipid syndrome.
AB  - OBJECTIVE: To study the outcome of pregnancies in women with primary and
      secondary recurrent pregnancy loss associated with antiphospholipid syndrome
      treated with the standard treatment regimes including intravenous immunoglobulin
      (IV Ig). METHODS: Forty three patients with recurrent pregnancy loss associated
      with antiphospholipid syndrome diagnosed before pregnancy and subdivided into
      primary (18) and secondary (25) subgroups were closely monitored all through
      pregnancy with serial blood tests and ultrasonography until the pregnancy ended
      in miscarriage or delivery. The patients were treated with low-dose aspirin and
      heparin and or steroids and IV Ig given to some selected patients. The maternal
      and fetal outcomes were analysed. RESULTS: The mean age of the patients in the
      primary subgroup (24.60 +/- 4.30) years was significantly lower than the mean age
      of the secondary recurrent pregnancy loss group (31.50 +/- 4.50) years, (p <
      0.0001). 85.00% of all the previous miscarriages were in the first trimester.
      There was no significant difference in the incidence of live births in the
      primary (77.80%) and secondary (84.00%) groups, (p > 0.05); the babies were of
      normal birth weight. The incidence of caesarean section in the primary and
      secondary groups, 22.23% and 12.00% respectively, were not significantly
      different (p > 0.05). Intravenous immunoglobulin added to the standard therapy
      resulted in 100% live births. Maternal complications were negligible.
      CONCLUSIONS: The fetal and maternal outcome of pregnancies in patients with
      primary and secondary recurrent pregnancy loss associated with antiphospholipid
      syndrome were virtually identical and quite satisfactory. Intravenous
      immunoglobulin added to the standard therapy resulted in excellent fetal and
      maternal outcome, although its definitive role will have to wait for the outcome
      of randomised trials.

PMID- 12049297
TI  - Human chorionic gonadotropin in human placentas from normal and preeclamptic
      pregnancies.
AB  - OBJECTIVE: The aim of this study was to examine the distribution of human
      chorionic gonadotropin (hCG) in the human placenta of normotensive and
      preeclamptic pregnancies and to determine by computer image analysis, whether
      differences in hCG immunoreactivity occurred in preeclamptic as apposed to
      normotensive pregnancies. We discuss how far elevated maternal serum levels of
      hCG normally observed in preeclamptic patients reflect an increased secretory
      activity of the syncytiotrophoblast. METHODS: We used the immunoperoxidase
      technique to locate hCG. Quantification of immunostaining intensity was done by
      computer image analysis. RESULTS: In normotensive placentas from all the
      gestational ages human chorionic gonadotrophin immunoreactivity was specifically
      detected in the syncytiotrophoblast. There is an apparent decrease in the
      intensity of the hCG immunostaining in the syncytiotrophoblast from the 29th to
      36th week of gestation in normotensive placentas. No hCG immunostaining was
      observed in the villous or extravillous cytotrophoblast of all placentas. In
      preeclamptic placentas the expression of hCG was homogeneous with a moderate to
      intense immunoreactivity in the syncytiotrophoblast. Microdensitometric analysis
      of the section from normotensive and preeclamptic placentas indicated that there
      is a statistically significant preeclampsia-induced increase in
      immunohistochemical reaction intensity for hCG (p < 0.05). CONCLUSION: This study
      seems to demonstrate that increased production of hCG by preeclamptic placentas
      is associated with strong hCG immunostaining of the syncytiotrophoblast.

PMID- 12049298
TI  - Hematological abnormalities in adolescent menorrhagia.
AB  - BACKGROUND: The purpose of this study is to determine the frequency of underlying
      hematological disorders as the cause of acute adolescent menorrhagia. METHODS:
      The records of 25 patients that were hospitalized with acute adolescent
      menorrhagia in the Obstetrics and Gynecology Department of Cerrahpasa Medical
      School of Istanbul University between 1988 and 1995 were analyzed. RESULTS: The
      mean age of the patients was 13.9 +/- 1.6 (SD) years. A hematological abnormality
      that caused bleeding diathesis and acute menorrhagia was diagnosed in 7 of the 25
      patients (28%). There were four cases of immune thrombocytopenic purpura, two
      cases of Van Willebrand disease and one case of acute promyelocytic leukemia. All
      seven patients with a coagulation disorder required blood transfusions and the
      mean hemoglobin level at presentation was 6.2 g/dl.

PMID- 12049299
TI  - Histopathological evaluation of the connective tissue of the vaginal fascia and
      the uterine ligaments in women with and without pelvic relaxation.
AB  - This study aimed to compare connective tissue components within the uterine
      ligaments histopathologically in women with and without pelvic relaxation. The
      tissue samples obtained from the histopathologic specimens of 24 patients with
      uterine descensus who underwent vaginal hysterectomy and from twenty-one patients
      with no pelvic relaxation, in whom total abdominal hysterectomies were performed
      for benign reasons, were used as the study and control groups, respectively. From
      each hysterectomy material, samples for histological examination were taken from
      the vaginal fascia and from the cardinal, the uterosacral and the round ligaments
      (4 samples for each patient). The amount of collagen, cellularity and elastic
      fibers within the connective tissue were evaluated and scored by the co-author
      pathologist. Mann-Whitney U and Student t tests were used for the statistical
      analysis. The patients with pelvic relaxation had significantly higher scores of
      collagen and fewer scores of cellularity within the connective tissue samples,
      compared with the ones without relaxation (p < 0.01, p < 0.01). It was concluded
      that decreased fibroblasts and increased collagen content might be the key
      factors associated with pelvic support disorders.

PMID- 12049300
TI  - Laparotomy or laparoscopic surgery? Factors affecting the surgeons choice for the
      treatment of ectopic pregnancy.
AB  - PURPOSE: In this study, we aim to compare the surgeons' choice on the ectopic
      pregnancy cases during the last four years. The differences between laparoscopy
      and laparotomy cases and the factors which directed the surgeon to choose either
      of the surgical methods were evaluated. METHODS: Our study comprises 135 patients
      who were diagnosed as ectopic pregnancy and were hospitalized in the Gynecology
      Department of Istanbul Medical Faculty during 1996-1999. RESULTS: During 1996
      1999 a total of 118 cases had been diagnosed as tubal ectopic pregnancy and had
      been treated surgically. Seventy three patients (62%) had been treated with
      laparotomy while the rest 45(38%) had been treated laparoscopically. When
      compared, the amount of intraabdominal free blood volume was significantly higher
      in laparotomy group [270.45 +/- 466.72 mL laparoscopy group - 889.75 +/- 714 mL
      laparotomy group, (p = 0.0001)]. When we considered haemoperitoneum amount
      according to the patients' parity, intraabdominal blood volume was interestingly
      higher in multiparas [507 +/- 599.32 mL nulliparas vs. 768.68 +/- 749.15 mL
      mulltiparas, (p = 0.044)]. The percent of cases with ruptured tubes was 64% for
      the laparotomy and 38% the laparoscopic cases; and the difference between two
      groups was significant (p = 0.0013). CONCLUSION: Our study implied that
      haemodynamic stability and less intraabdominal free blood affect the surgeons'
      decision between laparotomy and laparoscopy. Fewer multiparous patients are
      suitable for these criteria which leads to less laparoscopic surgery. These
      findings, which need to be clarified, lead to the idea of human factor affecting
      the surgeons' choice indirectly.

PMID- 12049301
TI  - Distribution of fibronectin, laminin and collagen type IV in the materno-fetal
      boundary zone of the developing mouse placenta. Experimental study.
AB  - OBJECTIVE: The objective of this study is to demonstrate the distribution of
      extracellular matrix components of fibronectin, laminin and collagen type IV in
      the materno-fetal boundary zone of the developing mouse placenta. MATERIAL AND
      METHODS: Mice fetuses and placentas were removed serially every day until the
      19th gestational day. Implantation sites were processed and stained by an
      immunohistochemical method by specific antiserums to fibronectin, laminin and
      collagen type IV. The distribution of the extracellular matrix components in
      cytotrophoblasts and giant cells of the developing mouse placenta were determined
      under light microscope. RESULTS: Fibronectin, laminin and collagen type IV
      immunostaining demonstrated a dynamic relationship changing day by day after the
      conception. At the 16th day cytotrophoblasts and giant cells were all positively
      stained by the extracellular matrix components. CONCLUSION: This study
      demonstrates that the regions of the developing mouse placenta produce
      specialized extracellular matrices which may contain different ratios of these
      polypeptides.

PMID- 12049302
TI  - Survey of genital lichen sclerosus in women and men.
AB  - We present the clinical and laboratory findings in 60 women and 42 men with
      lichen sclerosus.

PMID- 12049303
TI  - Treatment of uterine sarcoma. A survey of 49 patients.
AB  - PURPOSE: Surgery, radiotherapy and chemotherapy are employed in the treatment of
      uterine sarcoma. We claim to evaluate the role of radiotherapy in the treatment
      of uterine sarcoma. PATIENTS AND METHODS: We report a retrospective study of 49
      patients with uterine sarcoma treated from 1990-1999 at Masaryk Memorial Cancer
      Institute in Brno. All 49 patients had surgery, 19 (38.7%) had adjuvant
      radiotherapy and 25 (51%) had chemotherapy. Using the FIGO classification: 71.4%
      had stage I, 6.1% stage II, 16.3%, stage III and 6.1% stage IVa disease. 42.9% of
      tumors were mixed Mullerian tumors, 34.7% leiomyosarcomas and 22.4% endometrial
      stromal sarcomas. 12 cases (24.5%) had a local recurrence, 7 (14.3%) had
      hematogenous dissemination. There was an increased disease free interval (DFI)
      for patients treated with adjuvant radiotherapy (p = 0.005). The DFI was
      favourably influenced by the stage of the disease. Of 12 patients with a local
      recurrence only one had postoperative radiotherapy. Radiotherapy had an impact on
      overall survival (OS). The five-year OS probability was 51.6% without
      radiotherapy and 88.9% with radiotherapy (p = 0.0066). CONCLUSION: We conclude
      that postoperative radiotherapy in our series of patients diagnosed with uterine
      sarcoma has an impact on locoregional and disease-free progression intervals
      (LRFI, DFI) and overall survival (OS). The most important prognostic factor is
      the extend of the disease (stage). Stage I patients have a significantly better
      survival.

PMID- 12049305
TI  - DNA microarrays: a new diagnostic tool and its implications in colorectal cancer.
AB  - Effective treatment of colorectal cancer requires early detection and diagnostic
      and prognostic accuracy in characterizing patients of various risk groups. The
      development of DNA microarray makes it possible to analyze thousands of genes in
      a single tissue sample in one experiment and to characterize the biological
      behavior of colorectal cancer cells. Different cluster algorithms have been used
      to analyze large datasets on gene expression data, and initial results show
      significant differences between colorectal cancer and normal colon tissue.
      Although more than 6000 genes have been analyzed between colorectal cancer and
      normal tissue, different expression levels have been found in only 100-500
      transcripts depending on the cluster algorithm. Most transcripts belong to genes
      involved in cell growth regulation, differentiation of cells, ribosomal proteins
      or metalloproteinase. A future goal in microarray technology will be the
      development of clustered gene chips which characterize each tumor type
      specifically and focus on gene expression that specifies cell identity.

PMID- 12049304
TI  - Carotid pulsatility indices in surgical menopause.
AB  - A large body of literature is available concerning association of hormone
      replacement therapy (HRT) and postmenopausal women; to our knowledge, only few
      publications in purely surgical menopausal women. The aim of this study was to
      evaluate pulsatility indices (PI) of internal carotid arteries in two groups of
      surgical menopausal women who underwent HRT vs who did not. Measurements of the
      PIs of internal carotid arteries in both Groups were performed with color Doppler
      ultrasound. Measurements of the untreated group (n = 38, mean age = 47.10 +/-
      2.45, group 1) were compared to those of treated group (n = 42, mean age = 47.35
      +/- 2.37, group 2). A statistically significant increase in PIs of the carotid
      arteries were observed in Group 1 as compared to Group 2 in post-operative follow
      up (p < 0.001). Pre- and post-operative PIs in Group 1 measured at significantly
      different values pre- and post-operatively (right, 0.73 +/- 0.031 vs 0.80 +/-
      0.049; left, 0.73 +/- 0.030 vs 0.80 +/- 0.052) (p < 0.001). No such pre- and post
      operative difference in PIs were noted among patients in Group 2 (right, 0.74 +/-
      0.046 vs 0.73 +/- 0.044, p = 0.200; left, 0.73 +/- 0.04 vs 0.73 +/- 0.04, p =
      0.504). When comparing both groups, no statistical difference was noted pre
      operatively (right, p = 0.501; left p = 0.625); however, postoperative PIs did
      reveal a statistically significant difference (p < 0.05). Pre- and post-operative
      side-to-side differences in the PIs of internal carotid arteries were not
      statistically significant (group 1, 0.158 vs 0.211; group 2, 0.152 vs 0.356). In
      surgical menopausal women, the beneficial effects of HRT are in concordance with
      previous studies in terms of PI, which were performed with natural menopausal
      women.

PMID- 12049306
TI  - Lymphoscintigraphy in patients with primary rectal cancer: the role of total
      mesorectal excision for primary rectal cancer--a lymphoscintigraphic study.
AB  - BACKGROUND AND AIMS: Total mesorectal excision based operations is the gold
      standard of care in patients with middle and lower rectal cancer, but the extent
      of resection varies widely. In our view, extended lymphadenectomy is unnecessary
      with precise total mesorectal excision, i.e., anatomically correct and sharp
      surgery. PATIENTS AND METHODS: Sixteen patients with primary rectal cancer
      underwent rectal lymphoscintigraphy 1 day prior continence-preserving anterior
      resection with total mesorectal excision. The specimens were examined for
      integrity by postoperative angiography of the superior rectal artery in
      anteroposterior and lateral views. RESULTS: Twelve patients had only mesorectal
      lymph nodes, and four had additional extramesorectal iliac lymph nodes. The
      labeled lymph nodes were identified and removed perioperatively using a gamma
      probe. Activity was measured again in the preparations outside the situs.
      Histological examination showed tumor-free lymph nodes only. CONCLUSION: Lymph
      vessels can be divided anatomically into visceral and somatic, and detection of
      extramesorectal lymph nodes does not call for lateral lymphadenectomy. Primary
      rectal cancer confined to the organ metastasizes within the mesorectum and does
      not invade extraregional lymph nodes. The mesorectum is the major visceral route
      for caudocranial metastatic spread.

PMID- 12049307
TI  - Comparison of cyclo-oxygenase 2 expression in colorectal serrated adenomas to
      expression in tubular adenomas and hyperplastic polyps.
AB  - BACKGROUND AND AIMS: Serrated adenoma (SA) is a newly defined category of
      colorectal neoplasia that contains features of both adenoma and hyperplastic
      polyp, and has two patterns, hyperplastic and cerebriform patterns. Since
      cyclooxygenase 2 (COX-2) has been found upregulated in colorectal cancers and
      adenomas, we examined whether either the hyperplastic or cerebriform pattern of
      SA has the potential for tumor progression and should be a target for clinical
      treatment. PATIENTS AND METHODS: An immunohistochemical scoring system was used
      to compare COX-2 expression in colorectal SAs (n=79), tubular adenomas (n=66),
      and hyperplastic polyps (n=21). RESULTS: COX-2 scores were significantly higher
      in SA of the cerebriform pattern (n=44) than in SA of the hyperplastic pattern
      (n=35). There was no difference in COX-2 scores between SA of the cerebriform
      pattern and tubular adenoma. In SA accompanied by hyperplastic polyp (n=26) the
      hyperplastic components expressed little COX-2, the same as traditional
      hyperplastic polyps. COX-2 expression in the SA component was similar to that in
      pure SA. CONCLUSION: SA of the cerebriform pattern should be treated similarly as
      traditional tubular adenomas. COX-2 induction may additionally be involved in
      progression from hyperplastic polyp to SA.

PMID- 12049308
TI  - Stereotactic radiosurgery for brain metastases from colorectal cancer.
AB  - PURPOSE: The development of brain metastases represents an ominous event for
      patients with colorectal cancer. We evaluated results following stereotactic
      radiosurgery (SR) for patients with metastatic colorectal cancer to identify
      efficacy of SR and prognostic factors for survival. METHODS: This is a
      retrospective study of 60 brain metastases from colorectal cancer in 35
      consecutive patients who underwent SR from January 1993 to December 1996.
      Thirteen patients also underwent additional whole-brain radiation therapy (WBRT).
      The median dose delivered to the tumor margin was 20 Gray (range 16-28 Gy), in
      most cases the tumor enclosing the 50% isodose (range 40-60%). Patients were
      classified into two groups: SR with and SR without WBRT. Univariate and
      multivariate testing was performed to determine significant prognostic factors.
      RESULTS: The median survival time was 6 months after SR and 40 months after
      diagnosis of primary tumor. A Karnofsky performance scale >70 was a significantly
      favorable prognostic factor in uni- and multivariate testing. Post-SR imaging was
      evaluated in 32 patients and in 54 cerebral lesions. Local tumor control was
      revealed in 94% of patients and 96% of treated tumors. Two patients developed
      local recurrences, and remote brain disease was revealed in five. No patient
      experienced a new focal neurologic deficit due to SR. The addition of WBRT to SR
      did not improve survival and local tumor control rates. Distant control rate was
      borderline in univariate analysis and significantly improved for patients who
      received additional WBRT in multivariate analysis. CONCLUSION: SR for brain
      metastases from colorectal cancer results in a high local tumor control rate of
      94% associated with few complications and therefore provides patients with a
      higher quality of their remaining life.

PMID- 12049309
TI  - A carcinoid tumor associated with chylous ascites and elevated tumor markers.
AB  - The case is reported of a 74-year-old woman with a carcinoid tumor associated
      with chylous ascites and elevated tumor markers, CEA, and CA-125. In addition,
      the novel use of chromogranin-A quantitative assay from peripheral blood and
      ascetic fluid is discussed. The patient's clinical course and beneficial response
      to chemotherapy is also discussed and previous similar cases reported in the
      English-language literature are reviewed.

PMID- 12049310
TI  - Colorectal carcinoma in Poland in 1975 and 1995: not only more, but also
      different.
AB  - BACKGROUND AND AIMS: We previously reported that the sole clinicopathological
      parameters of carcinomas diagnosed in a single institution in 1975 differed from
      those in patients diagnosed in 1995. The findings might be compatible with the
      loss of importance of the microsatellite instability of the carcinogenic pathway.
      MATERIALS AND METHODS: We examined the microsatellite status and selected
      immunomarkers (Ki-67, p53, BAX) in the archival material from 1975 (n=76) and
      1995 (n=105). RESULTS AND CONCLUSION: The distribution of tumors showing no
      microsatellite instability, low microsatellite instability, and high
      microsatellite instability in the 2-yearly cohorts was similar (1975: 55.6%,
      22.2%, 22.2%; 1995: 60.2%, 20.4%, 19.4%, respectively). The percentage of
      carcinomas showing microsatellite instability at the APC locus differed
      significantly (1975: 37.5%; 1995: 21.4%). The typical clinicopathological
      parameters of carcinomas exhibiting high microsatellite instability were largely
      shared by the carcinomas demonstrating instability at the APC locus. The
      carcinomas resected in 1995 more frequently demonstrated high expression of an
      antiapoptotic protein BAX and a different distribution of their Ki-67
      proliferation fraction. The evolution of colorectal carcinoma in Poland also
      involves qualitative changes, including its genetic background.

PMID- 12049311
TI  - Enteral and intraluminal short-chain fatty acids improves ischemic left colonic
      anastomotic healing in the rat.
AB  - BACKGROUND AND AIMS: This study assessed the effect of short-chain fatty acids
      (SCFAs) on the healing of ischemic colonic anastomosis and compared the enteral
      and intraluminal (transrectal) forms of SCFAs in the same study. MATERIAL AND
      METHODS: Left colonic ischemia was induced and a 1-cm left colon resection 2-4 cm
      above the peritoneal reflection was performed through a midline incision. In all,
      160 rats were divided into eight groups: a control group, an ischemia group, a
      transrectal SCFAs group, an ischemia + transrectal SCFAs group, an enteral guar
      gum group, an ischemia + enteral guar gum group, an ischemia + enteral sham
      group, and a control + enteral sham group. The animals in each group were
      anesthetized again on day 4 or 7 after the operation for in vivo analytic
      procedures. Wound complications, intestinal obstructions, and anastomotic
      complications were recorded. Periperitoneal adhesions were graded. The strength
      of each anastomosis was assessed by measuring its bursting pressure. RESULTS:
      There were significantly more dense intra-abdominal adhesions in the ischemic
      group and ischemia + enteral sham group. Five animals in the ischemia group, six
      in the ischemia + enteral sham group, and one in each of the control and ischemia
      + transrectal SCFA groups developed anastomotic dehiscence. The median bursting
      pressures were significantly lower in the ischemic group and in the ischemia +
      enteral sham group on the 4 day and 7 days. CONCLUSION: Deleterious effects of
      ischemia on left colonic anastomotic healing were significantly prevented by the
      administration of either 7 days' pretreatment with enteral guar gum or the
      intraluminal instillation of SCFAs. There were no significant differences between
      enteral and intraluminal SCFA groups.

PMID- 12049312
TI  - Impact of age on the short-term postoperative outcome of patients undergoing
      surgery for colorectal carcinoma.
AB  - BACKGROUND: Patient age has a decisive impact on the short-term postoperative
      results in surgery for carcinoma. PATIENTS AND METHODS: This prospective
      multicenter study involved 75 German hospitals and 3756 patients undergoing
      treatment in 1999: 1447 aged under 65 years, 1847 aged 65-79 years, and 458 aged
      over 80 years. RESULTS: In the oldest patient group, there was a significantly
      higher proportion of extensive, localized tumors (UICC stage II: 25.9%, 28.4%,
      and 36.1%, respectively) and significant differences were found among the three
      groups in operation rates (98.8%, 98.6%, and 96.5%), resection rate (94.2%,
      93.2%, and 83.9%), general postoperative complications (21.5%, 28.6%, and 41.2%),
      morbidity (36.5%, 42.6%, and 50.0%) and mortality (2.7%, 6.6%, and 11.8%).
      CONCLUSION: In the elderly, locally advanced tumors, but not metastasizing
      tumors, are to be expected. The increase in postoperative morbidity and mortality
      rates with increasing age was due to the increase in general postoperative
      complications. Surgery for colorectal carcinoma in patients of advanced age is
      not associated with any increase in intraoperative or specific postoperative
      complications.

PMID- 12049313
TI  - Neurogenic appendicopathy: a clinical disease entity?
AB  - BACKGROUND AND AIMS: This study compared two histopathological examinations for
      the diagnosis of neurogenic appendicopathy (NA), assessed the frequency of NA,
      and evaluated whether it is a clinical disease entity distinct from acute
      appendicitis. PATIENTS AND METHODS: In a prospective observational multicenter
      study (surgical departments of five hospitals with one reference pathology) we
      evaluated 282 patients who underwent appendectomy for suspected appendicitis; we
      examined the frequency of NA in acute appendicitis and in the negative
      appendectomy group. For the diagnosis two staining methods were compared. We also
      attempted to determine clinical features of NA. RESULTS: We observed 93% accuracy
      for hematoxylin-eosin staining compared with S-100 staining (reference standard)
      in the diagnosis of NA. There was NA in 3.8% of patients with acute appendicitis
      and in 47% of those with negative appendectomy. We observed significant
      differences between the three groups (NA without appendicitis, acute
      appendicitis, and negative appendectomy without neurogenic appendicopathy) only
      for sex, age, vomiting, similar previous complaints, rebound tenderness,
      guarding, rigidity, leukocytes (univariate analysis) and sex (multivariate
      analysis). CONCLUSION: Neurogenic appendicopathy is a histopathological entity
      that can be identified by hematoxylin-eosin staining. History and clinical
      examination do not enable us preoperatively to differentiate between acute
      appendicitis, NA, and negative appendectomy.

PMID- 12049314
TI  - On the pathogenesis and clinical course of mesenteric lymph node cavitation and
      hyposplenism in coeliac disease.
AB  - BACKGROUND: Coeliac disease is a disorder characterised by malabsorption related
      to abnormal small bowel structure and intolerance to gluten. There are several
      reports of an increased risk for malignancy in coeliac disease and its relation
      to gluten-free, reduced gluten, or normal diet. While a normal diet is associated
      with an excess of cancer of the mouth, pharynx, oesophagus, and also of lymphoma,
      treatment with a gluten-free diet restores the cancer risk back to normal.
      PATIENT: In the present study, we report on a 63-year-old female patient with a
      history of coeliac disease for twenty years who presented with persistent
      diarrhoea, weight loss, and an abdominal mass. RESULTS: The gastroenterological
      work-up revealed small bowel mucosal atrophy, absence of functional splenic
      tissue, and evidence for an involution of a mesenteric lymph node, termed
      cavitation. DISCUSSION: This triad has been previously described to represent a
      rare disease entity related to coeliac disease. We report a two-year follow-up
      and a review of the literature on the pathogenesis, prognosis, and therapeutical
      implications of this disease entity.

PMID- 12049315
TI  - Sentinel lymph node biopsy in colorectal cancer: a bridge too far?

PMID- 12049316
TI  - Prognostic inhomogeneity in pT3 rectal carcinomas: comment.

PMID- 12049317
TI  - Learning of discriminations is impaired, but generalization to altered views is
      intact, in monkeys (Macaca mulatta) with perirhinal cortex removal.
AB  - Rhesus monkeys (Macaca mulatta) were taught a large number of visual
      discriminations and then either received bilateral removal of the perirhinal
      cortex or were retained as unoperated controls. Operated monkeys were impaired in
      retention of the preoperatively learned problems. To test for generalization to
      novel views, the monkeys were required to discriminate, in probe trials, familiar
      pairs of images that were rotated, enlarged, shrunken, presented with color
      deleted, or degraded by masks. Although these manipulations reduced accuracy in
      both groups, the operated group was not differentially affected. In contrast, the
      same operated monkeys were impaired in reversal of familiar discriminations and
      in acquisition of new single-pair discriminations. These results indicate an
      important role for perirhinal cortex in visual learning, memory, or both, and
      show that under a variety of conditions, perirhinal cortex is not critical for
      the identification of stimuli.

PMID- 12049318
TI  - Rearing experience differentially affects somatic and cardiac startle responses
      in rhesus monkeys (Macaca mulatta).
AB  - The present study reports, for the first time, somatic and cardiac responses to
      acoustic startle in 2 groups of rhesus monkeys (Macaca mulatta) with different
      rearing experiences. Both groups showed a significant direct relationship between
      startle amplitude and the intensity of the acoustic startle stimulus (80-120 dB)
      and rapid heart rate acceleration after a 120-dB stimulus. Monkeys reared with a
      same-age peer (PR) showed higher startle amplitudes than those reared with their
      mothers (MR), consistent with rearing effects in rodents. The MR monkeys,
      however, showed faster heart rate acceleration of greater overall magnitude than
      that of the PR group. The results are discussed with regard to a monkey model for
      neuropsychiatric disease.

PMID- 12049319
TI  - Impairment of executive function induced by hypertension in the rhesus monkey
      (Macaca mulatta).
AB  - The effects of chronic, untreated hypertension on executive function were
      investigated in a nonhuman primate model of hypertensive cerebrovascular disease.
      Executive function was assessed with the Conceptual Set-Shifting Task (CSST). a
      task adapted from the human Wisconsin Card Sorting Test (WCST). Like the WCST,
      the CSST requires abstraction of a stimulus set, followed by a series of set
      shifts. Performance on the CSST by 7 young adult monkeys (Macaca mulatta) with
      surgically induced hypertension was compared with that of 6 normotensive monkeys.
      The hypertensive group was significantly impaired relative to the normotensive
      group in abstraction and set shifting. Although the neural basis of this
      impairment is unclear, evidence from studies with humans and monkeys suggests
      that the prefrontal cortex may be the locus for this effect of hypertension.

PMID- 12049320
TI  - Tonic and phasic activation and arousal effects as a function of feedback in
      repetitive-choice reaction time tasks.
AB  - This study examines the effects of positive and negative feedback on performance
      during choice reaction time tasks to assess whether they differentially affect
      phasic arousal and tonic activation. Participants (N = 96) received either no
      feedback or signals of reward, punishment, or both during a semantic and a
      visuospatial repetitive-choice reaction time task. The number of errors made was
      analyzed both on a trial-by-trial basis and over a continuous series of 80 trials
      (assessing phasic and tonic feedback effects, respectively). The results show
      that punishment and reward have different phasic and tonic effects on
      performance. The data further show that feedback effects interact with the task
      characteristics: semantic versus visuospatial, and reaction stimulus preceded by
      a warning signal versus an irrelevant signal. The interaction effects appear to
      be consistent with the proposed neurological model.

PMID- 12049321
TI  - Are sex differences in navigation caused by sexually dimorphic strategies or by
      differences in the ability to use the strategies?
AB  - When navigating, women typically focus on landmarks within the environment,
      whereas men tend to focus on the Euclidean properties of the environment.
      However, it is unclear whether these observed differences in navigational skill
      result from disparate strategies or disparate ability. To remove this confound,
      the present study required participants to follow either landmark- or Euclidean
      based instructions during a navigation task (either in the real-world or on
      paper). Men performed best when using Euclidean information, whereas women
      performed best when using landmark information, suggesting a dimorphic capacity
      to use these 2 types of spatial information. Further, a significant correlation
      was observed between the mental rotation task and the ability to use Euclidean
      information, but not the ability to use landmark information.

PMID- 12049322
TI  - Estrogen-induced changes in place and response learning in young adult female
      rats.
AB  - Many findings suggest that changes in circulating estrogen levels influence
      cognition, in some cases impairing performance and in others enhancing
      performance. One interpretation of these mixed effects is that estrogen biases
      the strategy used to solve a task. To test this idea, young adult female rats,
      ovariectomized for 21 days, were trained after acute hormone or control treatment
      in 2 very similar tasks with different cognitive requirements. One task required
      place learning and the other response learning. Rats given two 10-microg
      injections of estradiol 48 and 24 hr before training learned the place task
      significantly faster than did rats without estradiol. Conversely, rats without
      estradiol performed better on the response task than did rats with replacement.
      These data suggest that the cognitive actions of estrogen may be task-specific by
      modulating the relative contribution of different learning and memory systems.

PMID- 12049323
TI  - Representations of odors in the rat orbitofrontal cortex change during and after
      learning.
AB  - Cells in the orbitofrontal cortex (OF) respond to odors and their associated
      rewards. To determine how these responses are acquired and maintained, the
      authors recorded single OF units in rats performing an odor discrimination task.
      Approximately 64% of all cells differentiated between rewarded and nonrewarded
      odors. These odor valence responses changed during learning in 26% of all cells,
      and these changes were positively correlated with improving performance,
      supporting the idea that the information provided by these cells is used in
      learning the task. However, changes in odor valence responses were also observed
      after learning, and included not only increases in odor discrimination, but also
      decreases or mixed increases and decreases. Thus, only some of the changes in
      firing reflected acquisition of the task. The results suggest that learning
      triggers a continuing reorganization of OF neural ensembles representing odors
      and their rewards.

PMID- 12049324
TI  - Reversible septal inactivation disrupts hippocampal slow-wave and unit activity
      and impairs trace conditioning in rabbits (Oryctolagus cuniculus).
AB  - This study investigated the effects of medial septal microinfusion of the local
      anesthetic, procaine (MS Pro), on hippocampal neurophysiology and learning of the
      rabbit (Oryctolagus cuniculus) classically conditioned jaw movement (CJM)
      response. Both the percentage and the amplitude of hippocampal theta decreased
      after procaine administration, and unit recordings from the MS Pro group showed
      significantly smaller conditioning-related hippocampal neural responses than
      those from controls. The MS Pro group took significantly longer to reach learning
      criterion than did the control group. Interpreted in the context of previous
      studies, the present result suggests that nonselective blocking of all septal
      projection systems, as well as fibers of passage, using procaine can be less
      detrimental to learning than an imbalance between GABAergic and cholinergic
      septohippocampal projections, as produced by septal infusion of anticholinergics.

PMID- 12049325
TI  - Visuospatial impairments in aged canines (Canis familiaris): the role of
      cognitive-behavioral flexibility.
AB  - This study used a novel delayed nonmatching-to-position task to compare
      visuospatial learning and memory in young and aged beagle dogs (Canis
      familiaris). The task used 3, rather than 2, spatial locations, which markedly
      increased difficulty. There were striking age differences in acquisition. Most of
      the aged canines did not learn the task, and those that did showed impaired
      learning when compared with the young canines. The aged canines also showed
      reduced maximal working memory capacity compared with the young canines. Analysis
      of the response patterns of individual canines indicated that the deficits were
      related to the use of ineffective strategies and inflexibility in strategy
      modification.

PMID- 12049326
TI  - Long-term potentiation and spatial learning are associated with increased
      phosphorylation of TrkB and extracellular signal-regulated kinase (ERK) in the
      dentate gyrus: evidence for a role for brain-derived neurotrophic factor.
AB  - In this study, the authors investigate changes in the presynaptic terminal of the
      dentate gyrus that accompany 2 types of hippocampal-dependent plasticity: spatial
      learning and long-term potentiation (LTP). Parallel changes occurred in the
      dentate gyrus of rats that had undergone training in the Morris water maze and
      had sustained LTP. In both cases, KCl-induced brain-derived neurotrophic factor
      release was increased, and this was accompanied by increased phosphorylation of
      TrkB and the mitogen-activated protein kinase, ERK. Glutamate release was also
      enhanced, and the data suggest that this may be a consequence of increased
      activation of TrkB and ERK. Because the data indicate that similar cellular
      modifications are shared by these 2 forms of plasticity, they provide
      circumstantial evidence that LTP satisfies some of the requirements of a memory
      inducing cellular substrate.

PMID- 12049327
TI  - Cognitive performance in rats differing in their inborn anxiety.
AB  - There is profound evidence that cognitive processes and anxiety are interrelated.
      To learn more about this interaction, the authors tested rats bred for either
      high (HABs) or low (LABs) anxiety-related behavior in a modified hole board task.
      This task allows parallel investigation of various cognitive processes and
      possibly related behavioral dimensions, both under baseline conditions and during
      cognitively stressful situations. The authors provide evidence that the degree of
      anxiety is differentially associated with enhanced performance for distinct
      informational processes in rats. As HABs and LABs did not differ in their anxiety
      related behavior after habituation, that is, in a familiar environment during
      appetitive learning, the authors conclude that anxiety behavior in naive HABs may
      be due to differential cognitive processing.

PMID- 12049328
TI  - Learning impairments of hippocampal-lesioned mice in a paddling pool.
AB  - Control mice rapidly learned to escape from shallow water in a paddling pool,
      which combined elements of the Morris water maze and the Barnes holeboard maze.
      The pool's transparent perimeter wall contained 12 exits, only 1 of which led to
      an escape tunnel. Learning was impaired in mice with cytotoxic lesions of the
      hippocampus. Probe trials suggested that the controls were using extramaze cues.
      When the exit was blocked, controls, but not hippocampals, spent more time
      searching in this previously correct sector. When the spatial location of the
      exit was changed, hippocampals escaped more quickly, as they showed no preference
      for the old location. These results may be useful in the assessment of
      hippocampal dysfunction, particularly in genetically manipulated mice.

PMID- 12049329
TI  - Contextual fear discrimination is impaired by damage to the postrhinal or
      perirhinal cortex.
AB  - Postrhinal (POR) or perirhinal (PER) cortex damage impairs acquisition and
      expression of contextual fear, but the nature of the impairment remains unclear.
      This study used a contextual fear discrimination paradigm that biased subjects
      toward using a configural, rather than an elemental, strategy to distinguish
      between 2 contexts, I of which was paired with a mild footshock. Control rats
      discriminated between 2 contexts when a combination of several cues could be used
      (Experiment 1), but not when individual sensory cues were manipulated (Experiment
      2). Rats with POR or PER lesions could not discriminate between the shock and no
      shock contexts when multiple cues differentiated the contexts (Experiment 3). The
      results indicate that both the POR and PER have a role in configural learning of
      contextual fear.

PMID- 12049330
TI  - Opioids and attachment in rhesus macaque (Macaca mulatta) abusive mothers.
AB  - This study investigated the role of the endogenous opioid system in maternal and
      affiliative behavior of group-living rhesus macaque (Macaca mulatta) mothers with
      a history of abusive parenting. Eighteen mothers received an injection of the
      opioid antagonist naltrexone or saline for 5 days per week for the first 4 weeks
      of the infant's life. After treatment, mother-infant pairs were focally observed.
      Naltrexone did not significantly affect infant abuse or other measures of
      maternal behavior. Naltrexone increased the amount of grooming received by
      mothers from other group members and reduced the mothers' rate of displacement
      activities such as scratching, yawning, and self-grooming. These results concur
      with previous primate studies in suggesting that opioids mediate the rewarding
      effects of receiving grooming and affect anxiety-related behaviors.

PMID- 12049331
TI  - Anxiolytic effects of cytotoxic hippocampal lesions in rats.
AB  - Rats with cytotoxic lesions of the hippocampus were given 3 anxiety tests: social
      interaction with a novel rat, the elevated zero-maze (a modification of the plus
      maze), and hyponeophagia (eating familiar and novel foods in a novel place).
      Marked anxiolytic effects were seen in the social interaction and hyponeophagia
      tests, but not on the zero-maze. These results confirm and extend previous
      experiments that used traditional lesion techniques. The zero-maze result was
      consistent with other experiments using the plus-maze, in which intrahippocampal
      administrations of pharmacological agents were not anxiolytic, although
      variability in ethological tests may also be a factor. As the hyponeophagia test
      used an elevated apparatus, as in the zero- and plus-mazes, the lack of a lesion
      effect in the zero-maze was unlikely to have been due to an inability to relieve
      height-induced anxiety.

PMID- 12049332
TI  - Involvement of the rat medial prefrontal cortex in novelty detection.
AB  - The prefrontal cortex in humans has been implicated in processes that underlie
      novelty detection and attention. This study examined the contribution of the rat
      medial prefrontal cortex to novelty detection using the targeting, or orienting,
      response (OR) as a behavioral index. Lesions to the medial prefrontal cortex
      (specifically the prelimbic and infralimbic cortices) influenced neither the OR
      to a novel visual stimulus from a localized light source (V1), nor the change in
      this OR over the course of a series of exposures to V1. However, after exposure
      to V1, the OR to a 2nd visual stimulus from the same source, V2, was more
      pronounced in control rats than in lesioned rats. These results suggest that the
      medial prefrontal cortex in the rat contributes to the process of novelty
      detection.

PMID- 12049333
TI  - Hybrid thyroid carcinoma with a coarse chromatin pattern and nuclear features of
      papillary thyroid carcinoma.
AB  - Hybrid follicular carcinoma (FC) and papillary thyroid carcinoma (PTC) have not
      been previously well described. Consecutive cases of 29 FC, 12 Hurthle cell
      carcinomas (HC), 247 PTC and 13 Hurthle cell PTC (HPTC) were reviewed with
      special attention to the coarse (CC) and fine chromatin patterns (FIC), as well
      as to the presence of nuclear grooves, pseudoinclusions or optically clear
      appearance. Limited nuclear features of PTC (LNF-PTC) are defined as areas of
      tumor with FIC in addition to some other nuclear features, but insufficient for
      the diagnosis of PTC. Tumors with nuclei showing an admixture of CC and PTC or
      LNFPTC were submitted for immunostaining for cytokeratin 19, HBME and Ret/PTC. FC
      and HC contained areas of LNFPTC in 25 tumors and focal PTC in 3 tumors. None of
      these cases was associated with lymph node metastasis. Areas with CC were found
      in 54 PTC and 3 HPTC. The rates of vascular invasion and distant metastasis
      tended to be higher for PTC with areas of coarse chromatin pattern than for PTC
      without such areas; however, the difference was not statistically significant.
      Immunoreactivity for cytokeratin 19 and HBME was moderate to strong for PTC and
      focal areas of PTC or LNFPTC in FC without Hurthle cell changes. Ret/PTC
      immunostaining was positive in areas of LNFPTC or focal PTC in three FC. Focal
      PTC or areas of LNFPTC are frequently seen in FC. Likewise, areas of CC are often
      present in PTC. The presence of these focal areas does not appear to change the
      clinical behavior of the tumor and therefore does not warrant a change of
      nomenclature.

PMID- 12049334
TI  - Ki-67 immunoreactivity, basic fibroblastic growth factor (bFGF) expression, and
      microvessel density as supplementary prognostic tools in low-grade astrocytomas.
      An immunohistochemical study with special reference to the reliability of
      different Ki-67 antibodies.
AB  - Low-grade diffuse astrocytomas are generally slow-growing tumors; however, they
      may progress to anaplastic astrocytomas or glioblastomas. As existing grading
      systems fail to distinguish these tumors, ongoing research strives to identify
      new prognostic markers. In this study, 22 adult patients with supratentorial
      diffuse astrocytomas, WHO grade II, were investigated to clarify whether
      proliferative activity, assessed by different Ki67 antibodies (MIB-1, NC-MM1, NC
      Ki67p, rahKi67), expression of basic fibroblast growth factor (bFGF) or
      microvessel density have prognostic power. The Ki67 antibodies revealed low
      proliferation indices (PI); however, there was a wide spread of values, ranging
      from 0.1% to about 10%. In general, a positive correlation between the different
      Ki67 PIs was found. In 12 of 22 cases, bFGF immunoreactivity was recorded.
      Microvessel density was generally low. MIB-1 PI was the only prognostic factor of
      statistical significance. Ki67 PI, obtained by using the monoclonal antibody MIB
      1, can thus serve as a prognostic factor capable of identifying subsets of low
      grade diffuse astrocytomas with a potentially more aggressive clinical behavior.

PMID- 12049335
TI  - Immunohistological analysis of mast cell numbers in the intratumoral and
      peritumoral regions of prostate carcinoma compared to benign prostatic
      hyperplasia.
AB  - Recently, some studies reported the presence of mast cells in various
      malignancies and their role in tumor growth. The aim of the study was to
      determine the utility of mast cell numbers in evaluating benign and malignant
      prostate lesions, and to ascertain whether there are variations in the numbers of
      mast cells with the Gleason grade. The relationship between mast cell numbers and
      patient age was also investigated. Retrospectively, 104 prostate specimens were
      examined for the presence of mast cells. The study group consisted of 57 benign
      prostatic hyperplasias and 47 prostate carcinomas. The paraffin sections were
      stained with anti-human mast cell tryptase immunohistologically. The numbers of
      positively staining cells in five high-power fields were counted, and their mean
      was calculated. There was no relationship found between mast cell numbers and age
      statistically. The mean mast cell numbers of the intratumoral region were
      significantly different from those of the peritumoral region (p = 0.0001). While
      the difference between benign hyperplasia and the intratumoral region was found
      to be significant (p = 0.0001), no difference between hyperplasia and the
      peritumoral region was noted (p = 0.762). There was no statistical difference
      between Gleason score groups (p = 0.452), and there was no interaction between
      score groups and intraperitumoral regions (p = 0.355).

PMID- 12049336
TI  - Apoptosis in epithelial ovarian tumors.
AB  - It is now recognized that apoptosis plays an important role in the pathogenesis
      of tumors. This study evaluated the extent of apoptosis in different grades of
      ovarian tumors and correlated it with the expression of apoptosis regulatory
      genes, p53 and bcl-2 and with the total proliferative compartment of the tumor
      defined by the expression of the proliferating cell nuclear antigen (PCNA).
      Apoptosis was evaluated by the TUNEL (Tdt-mediated dUTP biotin nick end
      labelling) assay. Expressions of p53, bcl-2 and PCNA were analyzed by
      immunohistochemistry. A negative correlation was observed between the expression
      of bcl-2 and the extent of apoptosis (r = -0.3336, p = 0.019). P53 accumulation
      directly correlated with the extent of apoptosis (r = 0.485, p = 0.00041). The
      labelling index of PCNA also showed correlation with expression of p53 (r = 0.49,
      p = 0.00000). Apoptosis was significantly higher in poorly differentiated tumors
      when compared to the well- and moderately-differentiated tumors (r = 0.49152, p =
      0.00034). Such poorly-differentiated tumors also showed high p53 overexpression
      and loss of bcl-2 expression. The present study thus provides evidence that
      dysregulation of apoptosis and its regulatory genes is associated with increasing
      malignant potential and may thus contribute to the pathogenesis of ovarian
      tumors.

PMID- 12049338
TI  - Abundant apoptosis in nutmeg liver of cardiomyopathic hamsters. Apoptotic cell
      death as a possible mechanism of hepatic remodeling by congestion.
AB  - Chronic congestive heart failure (CHF) causes structural remodeling of the liver,
      generally leading to nutmeg liver. Male UM-X7.1 hamsters, a strain developing
      cardiomyopathy, had no CHF and decompensated CHF (n = 6 each) at the age of 10
      and 30 weeks, respectively. We used age-matched, male Syrian hamsters without CHF
      (n = 6 each) as controls. All the 30-week-old UM-X7.1 hamsters had a typical
      nutmeg liver in which the population of hepatocytes was decreased. Positive in
      situ nick end labeling (TUNEL) was found in 2.2 +/- 0.74% of hepatocytes in
      congestive livers, being significantly higher compared with the other groups
      without CHF (< 0.5%). DNA ladder pattern was also evident in the congestive
      livers. Electron microscopy revealed a typical apoptotic ultrastructure in the
      hepatocytes of the 30-week-old UM-X7.1 hamsters. However, many showed secondary
      necrotic changes. Although hepatocytes undergoing oncosis (primary necrosis) are
      rare, they were also found. The level of soluble Fas ligand in the plasma was
      increased, and Fas receptor in the liver was overexpressed in the CHF animals. In
      addition, both the Bax/Bcl-2 ratio and the Bad/Bcl-xL ratio were increased, and
      caspase-3 was activated in them. Our findings suggest that hepatocyte apoptosis
      contributes to hepatic remodeling under conditions of CHF.

PMID- 12049337
TI  - Different preservation of myocardial capillary endothelial cells and
      cardiomyocytes during and after cardioplegic ischemia (25 degrees C) of canine
      hearts.
AB  - Complete resumption of cardiac function after cardioplegic arrest presupposes a
      well-preserved myocardial ultrastructure during and after ischemia. Therefore, we
      determined ischemia-induced ultrastructural alterations in the myocardium during
      and after reversible cardioplegic ischemia using stereological methods. Cardiac
      arrest was induced with St. Thomas' Hospital- or Custodiol (HTK) solution.
      Reperfusion with Tyrode's solution followed after reversible cardioplegic
      ischemia in situ. Samples were taken 1) from beating hearts, 2) from
      cardioplegically arrested hearts immediately after the end of coronary perfusion,
      3) from ischemic hearts incubated in the cardioplegic solution at 25 degrees C,
      and 4) from reperfused beating hearts after ischemia in situ at 22 degrees C.
      Cellular swelling was determined as the barrier thickness of capillary
      endothelium and as the sum of cardiomyocyte volume fractions of free sarcoplasm
      and mitochondria. In St. Thomas'-arrested hearts, intraischemic volume increase
      was significantly more pronounced in endothelial cells than in cardiomyocytes.
      Reperfusion at the intraischemic practical limit of resuscitability (ATP levels
      of 4 micromol/gww) significantly reduced intraischemic swelling of
      cardiomyocytes, but not of capillary endothelial cells. Mitochondrial damage was
      more pronounced in capillary endothelial cells during ischemia and after
      reperfusion. Thus, after reversible cardioplegic arrest, structural recovery of
      cardiomyocytes is better than that of capillary endothelial cells. An incomplete
      structural protection of capillary endothelial cells may predominantly contribute
      to postischemic dysfunction in the reperfused heart.

PMID- 12049339
TI  - Bone marrow extracellular large geometric crystals in IgG/lambda MGUS.
AB  - We describe the peculiar histopathology of the bone marrow in a case of
      IgG/lambda MGUS. Striking eosinophilic crystals with a rectangular, rhomboid or
      square shape lay in the interstitium, sometimes in optically empty spaces, but
      failed to elicit a foreign body giant cell reaction. Their histochemical
      properties, immunoreactivity for anti-lambda light chain antiserum, and
      ultrastructural features strongly supported their relationship with the
      paraprotein synthesized by the monoclonal plasma cells. The crystals were not
      observed on bone marrow aspirate smear, suggesting that they had formed during
      trephine biopsy processing or, alternatively, that they had been removed during
      the smear preparation. We feel that pathologists should be aware of the existence
      of this type of crystals, which differ from both the amyloid deposits and the
      proteinaceous material sometimes observed in plasma cell proliferations. Their
      presence in the bone marrow should alert the clinician to investigate the
      involvement of other organs with immunoglobulin deposits.

PMID- 12049340
TI  - Sclerosing mucoepidermoid carcinoma with eosinophilia of the salivary glands.
AB  - We encountered two cases of low malignant mucoepidermoid carcinoma with scanty
      cellular atypism which originated in the parotid or submandibular gland and was
      characterized by marked fibrosis and eosinophilic infiltration within tumor
      tissue despite the predominance of the squamous component. Here we report these
      two cases and provide a review of the literature. We believe that clinically
      these two tumors with stromal fibrosis and eosinophilic infiltration have a low
      malignant potential, although histological examination revealed a scanty mucus
      producing epithelial component. Therefore, we consider this type of tumor as a
      new subtype of mucoepidermoid carcinoma. A low-malignant mucoepidermoid carcinoma
      with stromal fibrosis and eosinophilic infiltration, as described in these two
      cases, may be misdiagnosed as a highly malignant mucoepidermoid carcinoma or
      squamous cell carcinoma because of its histologically scanty mucus-producing
      epithelial component. The objective of this study was to clarify their
      differences and to discuss the rendering of an accurate histological diagnosis,
      the degree of malignancy in relation to prognosis prediction, and the choice of
      therapy. In addition, we propose regarding this type of tumor as a new subtype of
      mucoepidermoid carcinoma.

PMID- 12049341
TI  - Epithelial plasma cell granuloma-like tumors of the lungs. A hitherto
      unrecognized tumor.
AB  - We present two cases of benign pulmonary epithelial tumors located in the middle
      lobes of the lungs. The patients were women of 56 and 36 years of age. The tumors
      were morphologically similar to plasma cell granuloma. At the tumor periphery,
      the lesion cells formed thin organoid rows of cells and vague trabeculae,
      disclosing morphologically their epithelial nature. In addition, the tumors
      strongly stained immunohistochemically with antibodies to cytokeratins, TTF-1 and
      EMA, and they were negative for immunoglobulin kappa and lambda light chains. We
      are not aware of similar tumors described in the literature, and we suggest the
      name "epithelial plasma cell granuloma-like tumors" for these lesions.

PMID- 12049342
TI  - Neural grouping and geometric effect in the determination of apparent
      orientation.
AB  - We propose that neural grouping of retinotopically distributed responses in the
      primary visual cortex (V1) is essential for the determination of apparent tilt,
      including the tilt illusion. Our psychophysical study shows that apparent tilt is
      independent of stereo disparity, hue, or contrast of bars, which determine the
      ownership of their intersection. This leads us to suspect that the neuronal
      responses within the intersection are excluded from the computation of apparent
      tilt. To investigate the underlying cortical mechanisms, we developed and
      examined a V1 network model including the collinear connections observed in the
      superficial layers. The model shows good agreement with the results of
      psychophysical experiments, including segmentation independence, contrast
      dependence, and apparent tilt for various stimuli. The results suggest that
      collinear connections underlie the neural grouping that excludes the intersection
      region and establishes the independence of segmentation.

PMID- 12049343
TI  - Ocular aberrations with ray tracing and Shack-Hartmann wave-front sensors: does
      polarization play a role?
AB  - Ocular aberrations were measured in 71 eyes by using two reflectometric
      aberrometers, employing laser ray tracing (LRT) (60 eyes) and a Shack-Hartmann
      wave-front sensor (S-H) (11 eyes). In both techniques a point source is imaged on
      the retina (through different pupil positions in the LRT or a single position in
      the S-H). The aberrations are estimated by measuring the deviations of the
      retinal spot from the reference as the pupil is sampled (in LRT) or the
      deviations of a wave front as it emerges from the eye by means of a lenslet array
      (in the S-H). In this paper we studied the effect of different polarization
      configurations in the aberration measurements, including linearly polarized light
      and circularly polarized light in the illuminating channel and sampling light in
      the crossed or parallel orientations. In addition, completely depolarized light
      in the imaging channel was obtained from retinal lipofuscin autofluorescence. The
      intensity distribution of the retinal spots as a function of entry (for LRT) or
      exit pupil (for S-H) depends on the polarization configuration. These intensity
      patterns show bright corners and a dark area at the pupil center for crossed
      polarization, an approximately Gaussian distribution for parallel polarization
      and a homogeneous distribution for the autofluorescence case. However, the
      measured aberrations are independent of the polarization states. These results
      indicate that the differences in retardation across the pupil imposed by corneal
      birefringence do not produce significant phase delays compared with those
      produced by aberrations, at least within the accuracy of these techniques. In
      addition, differences in the recorded aerial images due to changes in
      polarization do not affect the aberration measurements in these reflectometric
      aberrometers.

PMID- 12049344
TI  - Influence of Stiles-Crawford apodization on visual acuity.
AB  - The Stiles-Crawford effect (SCE) of the first kind has often been considered to
      be important to spatial visual performance in that it ameliorates the influence
      of defocus and aberrations. We investigated the influence of SCE apodization on
      visual acuity as a function of defocus (out to +/-2 D) in four subjects. We used
      optical filters, conjugate with the eye's entrance pupil, that neutralized or
      doubled the existing SCE. With an illiterate-E task, the influence of the SCE was
      more noticeable for myopic defocus than for hypermetropic defocus, was generally
      more noticeable for high-contrast than for low-contrast letters, and increased
      with increase in pupil size. The greatest influence on visual acuity of
      neutralizing the SCE, across the subjects and range of conditions, was
      deterioration of 0.06 (4-mm pupil), 0.16 (6-mm pupil), and 0.29 log unit (7.6-mm
      pupil).

PMID- 12049345
TI  - Psychophysical model of chromatic perceptual transparency based on substractive
      color mixture.
AB  - Variants of Metelli's episcotister model, which are based on additive color
      mixture, have been found to describe the luminance conditions for perceptual
      transparency very accurately. However, the findings in the chromatic domain are
      not that clear-cut, since there exist chromatic stimuli that conform to the
      additive model but do not appear transparent. We present evidence that such
      failures are of a systematic nature, and we propose an alternative psychophysical
      model based on subtractive color mixture. Results of a computer simulation
      revealed that this model approximately describes color changes that occur when a
      surface is covered by a filter. We present the results of two psychophysical
      experiments with chromatic stimuli, in which we directly compared the predictions
      of the additive model and the predictions of the new model. These results show
      that the color relations leading to the perception of a homogeneous transparent
      layer conform very closely to the predictions of the new model and deviate
      systematically from the predictions of the additive model.

PMID- 12049346
TI  - Spatial frequency, phase, and the contrast of natural images.
AB  - We examined contrast sensitivity and suprathreshold apparent contrast with
      natural images. The spatial-frequency components within single octaves of the
      images were removed (notch filtered), their phases were randomized, or the
      polarity of the images was inverted. Of Michelson contrast, root-mean-square
      (RMS) contrast, and band-limited contrast, RMS contrast was the best index of
      detectability. Negative images had lower apparent contrast than their positives.
      Contrast detection thresholds showed spatial-frequency-dependent elevation
      following both notch filtering and phase randomization. The peak of the spatial
      frequency tuning function was approximately 0.5-2 cycles per degree (c/deg).
      Suprathreshold contrast matching functions also showed spatial-frequency
      dependent contrast loss for both notch-filtered and phase-randomized images. The
      peak of the spatial-frequency tuning function was approximately 1-3 c/deg. There
      was no detectable difference between the effects of phase randomization and notch
      filtering on contrast sensitivity. We argue that these observations are
      consistent with changes in the activity within spatial-frequency channels caused
      by the higher-order phase structure of natural images that is responsible for the
      presence of edges and specularities.

PMID- 12049347
TI  - Effects of negative afterimages in visual illusions.
AB  - We show that a broad class of visual illusions, including illusory motion, can be
      explained by the effects of negative afterimages. Two new illusions, illusory
      shading and illusory tilting, are devised on the basis of the proposed
      explanation. The general feature of these illusions is an alternation between a
      high-contrast (white or black) and a low-contrast (gray) local input signal,
      which can be caused either by eye motion over patterns of varied luminance or by
      a change in such patterns over time. A simple model of the local signal dynamics
      qualitatively reproduces the illusory effects by adding the negative afterimage
      to the original visual stimulus.

PMID- 12049348
TI  - Wavelet networks for face processing.
AB  - Wavelet networks (WNs) were introduced in 1992 as a combination of artificial
      neural radial basis function (RBF) networks and wavelet decomposition. Since
      then, however, WNs have received only a little attention. We believe that the
      potential of WNs has been generally underestimated. WNs have the advantage that
      the wavelet coefficients are directly related to the image data through the
      wavelet transform. In addition, the parameters of the wavelets in the WNs are
      subject to optimization, which results in a direct relation between the
      represented function and the optimized wavelets, leading to considerable data
      reduction (thus making subsequent algorithms much more efficient) as well as to
      wavelets that can be used as an optimized filter bank. In our study we analyze
      some WN properties and highlight their advantages for object representation
      purposes. We then present a series of results of experiments in which we used WNs
      for face tracking. We exploit the efficiency that is due to data reduction for
      face recognition and face-pose estimation by applying the optimized-filter-bank
      principle of the WNs.

PMID- 12049349
TI  - Efficient analysis of periodic dielectric waveguides using Dirichlet-to-Neumann
      maps.
AB  - We present a numerical scheme for the analysis of periodic dielectric waveguides
      using Floquet-Bloch theory. The problem of finding the fundamental propagation
      modes is reduced to a nonlinear eigenvalue problem involving Dirichlet-to-Neumann
      maps. This approach leads to much smaller matrix problems than the ones that have
      appeared previously. By an increase of the discretization fineness, any desired
      precision of the method can be achieved. We discuss an eigensolver and extend the
      conventional rule to choose the branches of the transverse wave numbers. This
      ensures analytic dependence on the Floquet multiplier and convergence of the
      nonlinear solver. We demonstrate that even for a complicated multilayer waveguide
      structure the propagation factors can be calculated within seconds to several
      digits of accuracy.

PMID- 12049350
TI  - Step-transition perturbation approach for pixel-structured nonparaxial
      diffractive elements.
AB  - An extension of an approximate step-transition perturbation method is presented
      that permits numerically efficient diffraction analysis of pixel-structured
      surface profiles in the nonparaxial domain. Comparison with the rigorous
      diffraction theory of gratings shows that the method is reasonably accurate
      provided that the pixel size exceeds approximately two wavelengths even if the
      structure contains isolated pixels.

PMID- 12049351
TI  - Phenomenological theory of filtering by resonant dielectric gratings.
AB  - Using a phenomenological theory of diffraction gratings made by perturbing a
      planar waveguide allows us to deduce important properties of the sharp filtering
      phenomena generated by this kind of structure when the incident light excites a
      guided wave. It is shown that the resonance phenomenon occurring in these
      conditions acts on one of the two eigenvalues of the Hermitian reflection matrix
      only. As a consequence, we deduce a mathematical expression of the reflectivity
      and demonstrate that high-efficiency filtering of unpolarized light requires the
      simultaneous excitation of two uncoupled guided waves. Numerical examples are
      given.

PMID- 12049352
TI  - Analytical approximations in multiple scattering of electromagnetic waves by
      aligned dielectric spheroids.
AB  - In a dense medium, the failure to properly take into account multiple-scattering
      effects could lead to significant errors. This has been demonstrated in the past
      from extensive theoretical, numerical, and experimental studies of
      electromagnetic wave scattering by densely packed dielectric spheres. Here,
      electromagnetic wave scattering by densely packed dielectric spheroids with
      aligned orientation is studied analytically through quasicrystalline
      approximation (QCA) and QCA with coherent potential (QCA-CP). We assume that the
      spheroids are electrically small so that single-particle scattering is simple.
      Low-frequency QCA and QCA-CP solutions are obtained for the average Green's
      function and the effective permittivity tensor. For QCA-CP, the low-frequency
      expansion of the uniaxial dyadic Green's function is required. The real parts of
      the effective permittivities from QCA and QCA-CP are compared with the Maxwell
      Garnett mixing formula. QCA gives results identical to those with the mixing
      formula, while QCA-CP gives slightly higher values. The extinction coefficients
      from QCA and QCA-CP are compared with results from Monte Carlo simulations. Both
      QCA and QCA-CP agree well with simulations, although qualitative disagreement is
      evident at higher fractional volumes.

PMID- 12049353
TI  - Note on formulation of the enhanced scattering- (transmittance-) matrix approach.
AB  - The enhanced transmittance matrix approach developed by Moharam et al. [J. Opt.
      Soc. Am. A 12, 1077 (1995)] is reformulated in a concise and illuminating form in
      terms of scattering (reflection and transmission) matrices directly. Two
      equivalent recursive formulations, corresponding to their full- and partial
      solution approaches, are presented and extended to allow simultaneous
      determination of both reflected and transmitted amplitudes. The relationships
      between these formulations and the S-matrix algorithm, together with their
      relative efficiencies and usefulness, are ascertained and compared by means of
      compact formulas featuring parallel algebraic structures. It is made evident that
      given the eigenmode solutions, the enhanced approach is the most direct and
      efficient way for deducing global scattering matrices.

PMID- 12049354
TI  - Linear single-step image reconstruction in the presence of nonscattering regions.
AB  - There is growing interest in the use of near-infrared spectroscopy for the
      noninvasive determination of the oxygenation level within biological tissue.
      Stemming from this application, there has been further research in using this
      technique for obtaining tomographic images of the neonatal head, with the view of
      determining the level of oxygenated and deoxygenated blood within the brain.
      Because of computational complexity, methods used for numerical modeling of
      photon transfer within tissue have usually been limited to the diffusion
      approximation of the Boltzmann transport equation. The diffusion approximation,
      however, is not valid in regions of low scatter, such as the cerebrospinal fluid.
      Methods have been proposed for dealing with nonscattering regions within
      diffusing materials through the use of a radiosity-diffusion model. Currently,
      this new model assumes prior knowledge of the void region; therefore it is
      instructive to examine the errors introduced in applying a simple diffusion-based
      reconstruction scheme in cases where a nonscattering region exists. We present
      reconstructed images, using linear algorithms, of models that contain a
      nonscattering region within a diffusing material. The forward data are calculated
      by using the radiosity-diffusion model, and the inverse problem is solved by
      using either the radiosity-diffusion model or the diffusion-only model. When
      using data from a model containing a clear layer and reconstructing with the
      correct model, one can reconstruct the anomaly, but the qualitative accuracy and
      the position of the reconstructed anomaly depend on the size and the position of
      the clear regions. If the inverse model has no information about the clear
      regions (i.e., it is a purely diffusing model), an anomaly can be reconstructed,
      but the resulting image has very poor qualitative accuracy and poor localization
      of the anomaly. The errors in quantitative and localization accuracies depend on
      the size and location of the clear regions.

PMID- 12049356
TI  - Dependence of the wave-front aberration on the radius of the reference sphere.
AB  - Wave-front aberration is a basic characteristic of the imaging properties of
      optical systems. The value of the wave-front aberration is obtained by
      calculating the difference between the optical path lengths of the real wave
      front and the reference sphere. The general relations for calculated dependence
      of the wave-front aberration on the radius of the reference sphere are given.

PMID- 12049357
TI  - Fractional Fourier transformers through reflection.
AB  - We show that an arbitrary paraxial optical system, compounded with its reflection
      in an appropriately warped mirror, is a pure fractional Fourier transformer
      between coincident input and output planes. The geometric action of reflection on
      optical systems is introduced axiomatically and is developed in the paraxial
      regime. The correction of aberrations by warp of the mirror is briefly addressed.

PMID- 12049355
TI  - In vivo resonant Raman measurement of macular carotenoid pigments in the young
      and the aging human retina.
AB  - We have used resonant Raman scattering spectroscopy as a novel, noninvasive, in
      vivo optical technique to measure the concentration of the macular carotenoid
      pigments lutein and zeaxanthin in the living human retina of young and elderly
      adults. Using a backscattering geometry and resonant molecular excitation in the
      visible wavelength range, we measure the Raman signals originating from the
      single- and double-bond stretch vibrations of the pi-conjugated molecule's carbon
      backbone. The Raman signals scale linearly with carotenoid content, and the
      required laser excitation is well below safety limits for macular exposure.
      Furthermore, the signals decline significantly with increasing age in normal
      eyes. The Raman technique is objective and quantitative and may lead to a new
      method for rapid screening of carotenoid pigment levels in large populations at
      risk for vision loss from age-related macular degeneration, the leading cause of
      blindness in the elderly in the United States.

PMID- 12049358
TI  - Boundary element analysis of dielectric waveguides.
AB  - We apply the boundary element method to the analysis of optical waveguides. After
      summarizing constant and linear element algorithms for both two- and three
      dimensional simulations, we introduce a new recursive series procedure for
      constructing the diagonal matrix elements. We then demonstrate that our method
      can be employed to minimize the reflectivity of optical waveguide antireflection
      coatings with both straight and angled facets.

PMID- 12049359
TI  - Exact axial electromagnetic field for vectorial Gaussian and flattened Gaussian
      boundary distributions.
AB  - The exact expressions of the electromagnetic field pertinent to Gaussian and
      flattened Gaussian linearly polarized boundary distributions have been derived in
      closed-form terms for any point lying on the axis. The obtained results allow the
      fields to be predicted for an arbitrary transverse beam size. Numerical results
      showing the differences between the exact results and those obtained within the
      paraxial framework are also presented.

PMID- 12049361
TI  - Invariant polarimetric contrast parameters of coherent light.
AB  - Many applications use an active coherent illumination and analyze the variation
      of the polarization state of optical signals. However, as a result of the use of
      coherent light, these signals are generally strongly perturbed with speckle
      noise. This is the case, for example, for active polarimetric imaging systems
      that are useful for enhancing contrast between different elements in a scene. We
      propose a rigorous definition of the minimal set of parameters that characterize
      the difference between two coherent and partially polarized states. Indeed, two
      states of partially polarized light are a priori defined by eight parameters, for
      example, their two Stokes vectors. We demonstrate that the processing performance
      for such signal processing tasks as detection, localization, or segmentation of
      spatial or temporal polarization variations is uniquely determined by two scalar
      functions of these eight parameters. These two scalar functions are the invariant
      parameters that define the polarimetric contrast between two polarized states of
      coherent light. Different polarization configurations with the same invariant
      contrast parameters will necessarily lead to the same performance for a given
      task, which is a desirable quality for a rigorous contrast measure. The
      definition of these polarimetric contrast parameters simplifies the analysis and
      the specification of processing techniques for coherent polarimetric signals.

PMID- 12049360
TI  - Quantum-well enhancement of the Goos-Hanchen shift for p-polarized beams in a two
      prism configuration.
AB  - It is predicted that the Goos-Hanchen effect can be resonantly enhanced by
      placing a metallic quantum well (ultrathin film) at the dielectric-vacuum (air)
      interface. We study the enhancement of the phenomenon, as it appears in
      frustrated total internal reflection with p-polarized light, both theoretically
      and numerically. Starting from boundary conditions for the electromagnetic field,
      which in a self-consistent manner take into account the quantum-well dynamics, we
      derive new expressions for the amplitude reflection and transmission coefficients
      of light, and from these the stationary phase approximation to the Goos-Hanchen
      shifts is obtained. It is shown that large peaks appear in the Goos-Hanchen shift
      below the critical angle in reflection, and these are located at the minima for
      the energy reflection coefficient. Both positive and negative shifts may occur,
      and the number of peaks depends on the gap width. To determine the accuracy of
      the simple stationary phase approximation, we carry out a rigorous stationary
      energy-transport calculation of the Goos-Hanchen shift. Although the overall
      agreement between the two approaches is good, the stationary phase approach
      mostly overestimates the peak heights. For a Gaussian incident beam, the
      resonance displacement of the reflected beam can be as large as the Gaussian
      width parameter. It is suggested that the possible relation between the Goos
      Hanchen effect and the optical tunneling phenomenon in the two-prism
      configuration should be reinvestigated by depositing quantum wells on the glass
      vacuum interfaces to obtain a better spatial photon localization.

PMID- 12049362
TI  - In-depth resolution from multifrequency Born fields scattered by a dielectric
      strip in the Fresnel zone.
AB  - The achievable depth resolution in reconstructing the permittivity profile of a
      dielectric strip under the Born approximation when data are collected in the
      Fresnel zone is studied. We consider a rectilinear measurement aperture and an
      orthogonal and centered rectilinear investigation domain. The roles of the
      aperture extent and frequency diversity are highlighted.

PMID- 12049363
TI  - Vaccine preventable diseases and vaccination coverage in Australia, 1993-1998.
AB  - BACKGROUND: Since the introduction of childhood vaccination for diphtheria in
      1932 and the widespread use of vaccines to prevent tetanus, pertussis (whooping
      cough) and poliomyelitis in the 1950s, deaths in Australia from vaccine
      preventable diseases (VPDs) have declined by more than 99%. It is important,
      however, that the downward trend in morbidity and mortality from VPDs is
      maintained and carefully monitored, and that changes are interpreted in relation
      to vaccination coverage. AIM: This report aimed to bring together three national
      sources of routinely collected data on the morbidity and mortality
      (notifications, hospitalisations and deaths) from VPDs during the period 1993
      1998 for the 8 diseases then on the routine childhood vaccination schedule, and
      for 4 other diseases potentially preventable by childhood vaccination. It also
      examined vaccination coverage for the same period. METHODS: Data sources included
      notifications from the National Notifiable Diseases Surveillance System (NNDSS),
      hospitalisation data from the Australian Institute of Health and Welfare (AIHW)
      National Hospital Morbidity Database, deaths from the Australian Bureau of
      Statistics (ABS) Causes of Death Collection and vaccination coverage according to
      the Australian Childhood Immunisation Register (ACIR). All data sources were
      expected to have some limitations, the most important being under-reporting for
      notifications and vaccination encounters, and coding errors in the hospital
      morbidity data. RESULTS: Notifications for the 8 diseases covered by the routine
      schedule declined by 42%, from an average of 11,537 cases each year in 1993-1997
      to 6700 in 1998, and hospitalisations fell by 12%, from an average of 1745 per
      year to 1536 in 1997/1998, while deaths remained unchanged at 7 each year over
      the period of review (Table 1). Tetanus caused 1 or 2 of the deaths each year.
      However, 6 of the 7 deaths in 1997 were in infants during a major outbreak of
      pertussis. Pertussis caused most of the notifications, hospitalisations and
      deaths during the review period. While most of these were in children, 46% of the
      notifications and 13% of the hospitalisations occurred in persons aged 15 years
      or more. There were notable declines in the numbers of notifications of invasive
      Haemophilus influenzae type b (Hib) disease in children under 5 years of age
      (77%), measles (87%) and rubella (75%), and there were no notifications of
      diphtheria or poliomyelitis. Vaccination coverage estimated using ACIR data
      increased during the review period. Coverage for the first 3 doses of diphtheria,
      tetanus, pertussis and Hib vaccines, assessed at 1 year of age, increased from
      75% to 85%, while coverage for measles-mumps-rubella (MMR) vaccine, assessed at 2
      years of age, increased from 83% to 86%. It is likely that these data
      underestimated coverage by 5-10%, and that the increase in coverage partly
      reflected better reporting to the ACIR by providers.

PMID- 12049364
TI  - The fiftieth anniversary of cardiac pacing.

PMID- 12049365
TI  - Atrial activation sequence during junctional tachycardia induced by thermal
      stimulation of Koch's triangle in canine blood-perfused atrioventricular node
      preparation.
AB  - Junctional tachycardia is observed during radiofrequency ablation of the slow
      pathway. The authors investigated the atrial activation sequence during
      junctional tachycardia induced with thermal stimulation in canine blood-perfused
      atrioventricular node (AVN) preparation. The canine heart was isolated (n = 7)
      and cross-circulated with heparinized arterial blood of the support dog. The
      activation sequence in the region of Koch's triangle (15 x 21 mm) was determined
      byrecording 48 unipolar electrograms. Atrial sites anterior to the coronary sinus
      ostium (site AN), close to the His-potential recording site (site N) and superior
      to site N (site F), were subjected to a continuous temperature rise from 38
      degrees C to 50 degrees C with a heating probe. The temperature of the tissue
      adjacent to the heating site was monitored simultaneously. Junctional tachycardia
      at a rate of 92+/-12 beats/min with the His potential preceding the atrial one in
      the His-bundle electrogram was induced during thermal stimulation at site AN
      (temperature 42.1 degrees C+/-0.9 degrees C) in all seven preparations, whereas
      junctional tachycardia was induced during stimulation at site N in one and at
      site F in none. In each case, the temperature rose only at the site of
      stimulation. The earliest activation site during junctional tachycardia induced
      by site AN stimulation was at the His-potential recording site in five
      preparations and the middle of Koch's triangle in the other two. After creating
      an obstacle between sites AN and N, atrial tachycardia at a rate of 85+/-11
      beats/min was induced during site AN stimulation. The earliest activation site
      during this tachycardia was site AN. Thus, junctional tachycardia induced by
      thermal stimulation was suggested to originate from the AN thermal stimulation
      site. The impulse from the stimulation site appeared to conduct via the posterior
      input to the compact AVN and junctional tachycardia was generated. When the
      posterior input was interrupted, atrial tachycardia was generated.

PMID- 12049366
TI  - Development of an echocardiographic method for choosing the best fitting single
      pass VDD lead.
AB  - To achieve stable single-lead VDD pacing, a selection of the electrode with the
      optimal distance between the lead tip and the floating atrial dipole (AV distance
      [AVD]) is important. The authors hypothesized that the size of the right heart
      chambers may affect atrial sensing, and that measurement of their internal
      dimension at end-diastole (RHIDd) in the apical four chamber view by
      transthoracic echocardiography may aid in choosing the proper AVD. Twenty-six
      consecutive cases that had undergone VDD pacer implantation using the
      conventional chest X ray were examined retrospectively by the echocardiographic
      method. The chest x-ray method properly selected a lead with optimal atrial
      sensing, defined as minimum P wave amplitude > or = 1.0 mV, for only 20 (77%) of
      26 patients. By comparing these results with their respective RHIDd, a cut-off
      point of 13 cm was obtained that indicated a criterion for choosing the proper
      AVD. The indication was that if the RHIDd was > or = 13 cm, a lead with an AVD of
      15.5/16 cm should have been used; if the RHIDd was < 13 cm, a lead with an AVD of
      13/13.5 cm should have been chosen. Using the echocardiographic method, all six
      patients who had suboptimal atrial sensing could be identified and classified as
      having missized (four undersized; two oversized) permanent leads. In conclusion,
      the described method provides a promising preoperative assessment of the best
      fitting electrode length in single lead VDD pacing. A prospective study is
      ongoing to verify its applicability.

PMID- 12049368
TI  - Importance of using standard rather than torso surface electrocardiographic leads
      for pacemapping at the right ventricular outflow tract.
AB  - Although pacemapping has been used to localize the origin of ventricular
      tachycardia, the effect of changes in the position of ECG electrodes during
      ventricular pacing remains unknown. To clarify the relationship between the
      position of ECG limb electrodes and QRS configuration during pacemapping at the
      right ventricular outflow tract (RVOT), RVOT pacing was performed on 12 patients
      at eight pacing sites located in the anterior, septal, lateral, and posterior
      portions each in the high and low RVOT. Standard and torso ECGs were recorded
      simultaneously during each pacing protocol, and the QRS axis and amplitude were
      compared between the two ECGs. Differences between sites in the horizontal plane
      and in the longitudinal direction were also compared. The QRS axis on the torso
      ECG was significantly more rightward than that on the standard ECG at all eight
      pacing sites (72.1+/-17.4 vs 64.0+/-21.9 degrees). The magnitude of differences
      in the QRS axis and amplitude between the anterior and other sites at the same
      height was significantly greater in the standard ECG in all locations and in 7 of
      18 comparable leads, respectively. The magnitude of differences between high and
      low sites was significantly greater in the standard ECG in three of four
      locations and in 5 of 12 comparable leads, respectively. In conclusion, the torso
      ECG is less sensitive to changes in pacing site at the RVOT than the standard
      ECG. The torso ECG is, therefore, not proper for pacemapping in attempts to
      ablate ventricular tachycardia arising from the RVOT.

PMID- 12049367
TI  - Increased dispersion of ventricular repolarization during head-up tilt test late
      after orthotopic heart transplantation in humans.
AB  - Sympathetic reinnervation after heart transplantation may be regionally
      heterogeneous. It remains undetermined if such heterogeneous reinnervation will
      result in increased ventricular repolarization dispersion. To determine the
      changes of ventricular repolarization after transplantation, a 15-minute, 80
      degree head-up tilt test was prospectively performed with isoproterenol
      provocation in 30 patients who were studied within 5 months after transplantation
      (early group) and 30 patients who were studied > or =12 months (late group).
      Holter monitor was initiated to evaluate heart rate variability, which was a
      surrogate of cardiac reinnervation. JT dispersion was defined as the difference
      between maximal and minimal JT interval measurements occurring among any of the
      12 leads on a standard electrocardiogram. No subject had fewer than nine
      measurable leads. Compared with patients in the early group, the patients in the
      late group had higher low frequency activity, indicating partial sympathetic
      reinnervation. Analysis of the electrocardiogram showed that there were
      significant differences in the corrected JT dispersion in the late group compared
      with the early group and controls (74+/-18 vs 56+/-15 and 55+/-14 ms, both P
      <0.05) during isoproterenol infusion. Head-up tilt test is a useful tool to
      unmask the increased dispersion of ventricular repolarization, particularly
      during states of isoproterenol infusion. Early after cardiac transplantation,
      neither postural changes nor isoproterenol infusion caused a significant increase
      of corrected JT dispersion. Late after transplantation, heterogeneous sympathetic
      reinnervation may result in increased corrected JT dispersion. However, whether
      increased dispersion of ventricular repolarization is related to cardiac death
      late after operation warrants further investigation in a large and long-term
      trial.

PMID- 12049369
TI  - Left atrial tachyarrhythmia in fetal lambs.
AB  - To evaluate the hemodynamic effect of rapid left atrial pacing on fetal
      circulation, a fetal supraventricular tachyarrhythmia model was made and the
      aortic pressure, central venous pressure, and left and right ventricular outputs
      were measured in ten fetal lambs. Under maternal anesthesia, the uterus was
      opened, and under local anesthesia, catheters were inserted into thefetal
      superior vena cava and ascending aorta through a neck incision. Pacing leads were
      then sutured onto the fetal left atrial appendage via left thoracotomy.
      Ventricular output was estimated using echocardiography by a transuterine
      approach. Fetal hemodynamics were observed without pacing (control), and at the
      pacing rates of 200, 300, 350, and 400/min. The aortic pressure decreased when
      the left atrium was paced at 300/min or more and the central venous pressure
      increased when the left atrium was paced at 350/min or more. The left and right
      ventricular outputs decreased when the left atrium was paced at 350/min or more.
      The left ventricular output was 215+/-54 mL/kg per minute at control, 205+/-60
      mL/kg minute when paced at 200/min, 178+/-58 mL/kg per minute when paced at
      300/min, but decreased to 164+/-44 mL/kg per minute when paced at 350/min and to
      149+/-57 mL/kg per minute when paced at 400/min. The right ventricular output was
      338+/-66 mL/kg per minute at control, 336+/-95 mL/kg per minute when paced at
      200/min, 273+/-91 mL/kg per minute when paced at 300/min, but decreased to 256+/
      80 mL/kg per minute when paced at 350/min and to 202+/-76 mL/kg per minute when
      paced at 400/min. Fetal circulatory failure was initially confirmed when the left
      atrium was paced at 300/min in this left atrial tachyarrhythmia model.

PMID- 12049370
TI  - Arrhythmic risk stratification after myocardial infarction using ambulatory
      electrocardiography signal averaging.
AB  - Ambulatory ECG had been proposed to examine the amplified high resolution signal
      averaged electrocardiogram (SAECG). Clinical investigations are required to
      confirm the predictive value of such a high resolution technique in arrhythmic
      risk stratification. The prognostic value of ambulatory Holter SAECG was
      evaluated in 108 postinfarction patients for the purpose of predicting the
      occurrence of serious arrhythmic (SARR) events (sudden cardiac death [SCD], VT,
      or VF) in comparison with classical real-time SAECG. During the 42+/-8 months of
      follow-up, the sudden cardiac death mortality was 4.6% (five deaths), six (5.6%)
      patients had VT, and one (0.9%) VF. QRSd was found to be the most predictive
      parameter using ROC curves analysis for SAAR + outcome (W = 0.833 and W = 0.803
      for 25-250 Hz and 40-250 Hz filters, respectively) followed by RMS (W = 0.766 and
      W = 0.721) and LAS (W = 0.759, W = 0.709) (all P < 0.01). Abnormal Holter SAECG
      for 25 and 40-Hz LP filter were significant predictors of SARR+ by log-rank test
      (P < 0.01, P < 0.05, respectively). This study confirms that valuable prognostic
      information can be obtained from the ambulatory high resolution ECG technique and
      that Holter SAECG may predict arrhythmic risk in a postinfarction population.

PMID- 12049371
TI  - Irrigated tip catheter ablation in right posteroseptal accessory pathways
      resistant to conventional ablation.
AB  - Although RF ablation is an effective treatment of arrhythmias due to
      atrioventricular accessory pathways, there are cases refractory to conventional
      catheter ablation. Irrigated tip catheter ablation causes larger and especially
      deeper lesions than conventional ablation. This article discusses using irrigated
      tip catheter ablation in cases of right posteroseptal accessory pathways
      resistant to conventional ablation. Four consecutive patients with no structural
      heart disease and symptomatic arrhythmias related to right posteroseptal
      accessory pathways underwent irrigated tip catheter ablation. Conventional RF
      ablation had been unsuccessful in at least two procedures at more than one center
      (in three patients at the authors' center). The irrigated tip catheter (Chilli,
      Cardiac Pathways Corporation) uses a cooling system that is a closed circuit with
      a saline solution circulating at 0.6 mL/s. Temperature, power, and impedance were
      monitored during the RF applications. The procedure was successful in all four
      cases with no complications. In three of them, only one or two applications were
      necessary. Patients showed no recurrent arrhythmia during several months of
      follow-up. The results of the present study suggest that RF ablation using an
      irrigated tip catheter can be useful (and seems to be safe) for the treatment of
      some right posteroseptal accessory pathways resistant to conventional ablation.

PMID- 12049372
TI  - Clinical study of the laser sheath for lead extraction: the total experience in
      the United States.
AB  - The laser sheath uses optical fibers, delivering pulsed ultraviolet excimer laser
      light, to vaporize fibrotic tissue binding intravenous cardiac leads to the vein
      or heart wall during lead extraction from the implant vein. The total
      investigational experience with laser sheaths is reported. During the period from
      October 1995 to December 1999, 2,561 pacing and defibrillator leads were treated
      in 1,684 patients at 89 sites in the United States with three sizes of laser
      sheath. Endpoints were complete removal of the lead, partial removal (leaving the
      tip behind), or failure (abandoning the lead, onset of complications, change to
      transfemoral or transatrial approach). Minimal follow-up at 30 days was recorded.
      Of the leads, 90% were completely removed, 3% were partially removed, and the
      balance were failures. Major perioperative complications (tamponade, hemothorax,
      pulmonary embolism, lead migration, and death) were observed in 1.9% of patients
      with in hospital death in 13 (0.8%). Minor complications were seen in an
      additional 1.4% of patients. Multivariate analysis showed that implant duration
      was the only preoperative independent predictor of failure; female sex was the
      only multivariate predictor of complications. Success and complications were not
      dependent on laser sheath size. At follow-up, various extraction related
      complications were observed in 2% of patients. The learning curve showed a trend
      toward fewer complications with experience. Lead extraction with the laser sheath
      can be safely practiced with high success rates. Success is independent of laser
      sheath size. Major complications can be expected in < 2% of patients, and occur
      more often during an investigator's early experience.

PMID- 12049373
TI  - Effect of coexisting cardiovascular disease on the long-term efficacy and safety
      of the implantable atrial defibrillator.
AB  - The long-term efficacy and safety of implantable atrial defibrillator (IAD)
      therapy in patients with AF and cardiovascular disease is unclear. The aim of
      this study was to evaluate the efficacy and safety of IAD therapy in patients
      with and without coexisting cardiovascular disease. In 115 patients implanted
      with an IAD, 85 patients had cardiovascular disease: 41 (48%) patients had 1
      cardiovascular abnormality, 29 (35%) patients had 2, 13 (15%) patients had 3, and
      2 (2%) patients had 4 different cardiovascular abnormalities. The device was
      programmed into a rhythm monitoring mode for the first 3-month postimplant
      period. All defibrillation therapy was performed under physician supervision to
      monitor safety and efficacy. After this initial monitoring period, patients were
      allowed to activate their device away from the hospital or clinic. A total of 357
      spontaneous AF episodes occurred in 83 (72%) patients during observed operation
      and the mean shock efficacy was 93.5+/-20.3% (lower 95% confidence interval [CI]
      89.8%). As of the lastfollow-up, 58 (55%) patients had transition to receive
      nonphysician observed therapy. Forty-two (72%) patients had experienced 332
      episodes of AF for which theyhad received device therapy away from the
      hospital/clinic (mean shock efficacy 90.5+/-39.7%). The presence of hypertension,
      valvular heart disease, and ischemic heart disease did not affect the shock
      efficacy of the IAD during physician observed and nonobserved therapy (P > 0.05).
      However, the presence of congestive heart failure was associated with a lower
      clinical efficacy during observed and nonobserved therapy (P < 0.05). Overall,
      5,262 shocks have been delivered with the IAD without any episode of
      proarrhythmia. The observed proarrhythmic risk was 0%, with an estimated maximum
      proarrhythmic risk of 0.06% per shock (95% upper CI). A stand-alone IAD appears
      to be safe in the presence of cardiovascular disease. The lower clinical efficacy
      for AF associated with congestive heart failure might be related to a higher rate
      of early reinitiation of AF after defibrillation.

PMID- 12049374
TI  - A randomized and controlled pilot trial of beta-blockers for the treatment of
      recurrent syncope in patients with a positive or negative response to head-up
      tilt test.
AB  - The aim of this study was to assess the efficacy of lipophilic beta-blockers in
      preventing recurrent neurocardiogenic syncope and the value of head-up tilt test
      (HUT) in predicting response to therapy. The efficacy of beta-blockers in
      recurrent syncope is controversial. The value of HUT in predicting efficacy of
      therapy has not been investigated. Fifty-six patients (44+/-18 years, 36 women)
      with recurrent syncope (> 1 event in the last 6 months) of suspected
      neurocardiogenic origin were included in the study. Independent of the response
      to HUT, patients were randomized to receive metoprolol or propanolol at the
      maximal tolerated dose (28 patients, group A, 86+/-23 vs 98+/-29 mg/d) or no
      pharmacological therapy (28 patients, group B). The primary endpoint was the
      first recurrence of syncope. During the 1-year of follow-up, 20 patients of group
      A and 8 of group B had no recurrence. In group A, of 20 patients without
      recurrences 12 had a positive and 8 a negative HUT result while of 8 patients
      with recurrences 5 had a positive and 3 a negative response to HUT. In the group
      B, of 20 patients with recurrences 10 had a positive and 10 a negative HUT result
      while of 8 patients without recurrences 4 had a positive and 4 a negative
      response to HUT. In a multivariate Cox-regression analysis, medical therapy was
      the only independent factor for predicting recurrence of syncope (P = 0.004); HUT
      had no influence in this regard (P = 0.773). In conclusion, lipophilic beta
      blockers appear efficacious in preventing recurrent syncope of suspected
      neurocardiogenic origin. The efficacy of therapy seems to be not predicted by
      HUT.

PMID- 12049375
TI  - Comparison of the performance of three diagnostic algorithms for regular broad
      complex tachycardia in practical application.
AB  - The authors previously proposed a Bayesian approach to the electrocardiographic
      diagnosis of regular broad complex tachycardia (BCT), which can be due to VT or
      supraventricular tachycardia with aberrant conduction (SVTAC). They also
      published an account comparing the theoretical merits in the design of two of the
      most commonly used diagnostic algorithms for the same purpose, those of Brugada
      et al. and Griffith et al. In this study, a direct head-to-head comparison was
      performed on the practical performances of the three algorithms in this study. A
      set of 111 ECGs showing regular BCT (77 VT, 34 SVTAC) whose diagnoses were
      confirmed by electrophysiological study was shown to five internists in general
      medicine at a district general hospital. The observers were asked to comment on
      whether the ECG criteria in the three algorithms tested were fulfilled or not,
      and a computer program then derived the corresponding diagnoses. The sensitivity
      and specificity for VT achieved by the Brugada algorithm were 92% and 44%, 92%
      and 44% by the Griffith algorithm, and 97% and 56% by the Bayesian algorithm. The
      Bayesian algorithm achieved a higher sensitivity and specificity than the other
      two algorithms, but the differences are not statistically significant (P = 0.6583
      and P = 0.5334, respectively). The Brugada, Griffith, and Bayesian algorithms
      show comparable performances in terms of overall sensitivity and specificity when
      tested in practice. Of the three algorithms, the Griffith algorithm excels in
      simplicity and is the easiest to implement in practice. The Bayesian algorithm
      achieved slightly higher values for sensitivity and specificity than the Brugada
      and Griffith algorithms but may be more suitable for automated computer-aided
      diagnosis of ECG due to its complexity.

PMID- 12049376
TI  - Nitroglycerin induced syncope occurs in subjects with delayed phase shift of
      baroreflex action.
AB  - Nitroglycerin (NTG) administration occasionally leads to syncope due to severe
      hypotension and bradycardia. This reaction resembles neurocardiogenic syncope but
      it may occur when the patient is in the supine position. To address the possible
      role of prevailing autonomic tone and baroreflex control in precipitation of NTG
      induced syncope, continuous noninvasive blood pressure and an ECG were taken
      shortly before NTG application in the supine position. Frequency-domain measures
      of heart rate variability (HRV) and noninvasive indices of baroreflex were
      compared between subjects who did (n = 6) and did not (n = 41) develop syncope
      after NTG. Both groups differed only in the phase shift (P(CR)) between
      oscillations of blood pressure and heart rate during controlled respiration (0.1
      Hz). P(CR) was significantly delayed in subjects who developed syncope than in
      controls (- 99.3+/-14.1 vs -65.5+/-27.0 degrees, P = 0.002). Thus, subjects with
      prolonged P(CR) are prone to NTG induced syncope because of increased lagging
      and, consequently, less stable baroreflex control.

PMID- 12049377
TI  - Postpacemaker implant pericarditis: incidence and outcomes with active-fixation
      leads.
AB  - Pericarditis has been noted as a potential complication of pacemaker
      implantation. This study evaluated the risk of developing pericarditis following
      pacemaker implantation with active-fixation atrial leads. Included were 1,021
      consecutive patients (mean age 73.4+/-0.4 years, range 16-101 years; 45.2% women)
      undergoing new pacemaker system implantation between 1991 and 1999 who were
      reviewed for the complication of pericarditis. The incidence and outcomes of
      postimplantation pericarditis in patients receiving active-fixation atrial leads
      were compared to those not receiving these leads. Of 79 patients who received
      active-fixation atrial leads, 4 (5%) developed pericarditis postpacemaker
      implantation. Of 942 patients with passive-fixation atrial leads or no atrial
      lead (i.e., a ventricular lead only), none developed pericarditis postoperatively
      (P < 0.001). Of patients receiving active-fixation ventricular leads only (n =
      97), none developed pericarditis. No complications were apparent at the time of
      implantation in patients who developed pericarditis. Pleuritic chest pain
      developed between 1 and 28 hours postoperatively. Three patients had pericardial
      rubs without clinical or echocardiographic evidence of tamponade. They were
      treated conservatively with acetylsalicylic acid or ibuprofen and their symptoms
      resolved without sequelae in 1-8 days. One patient (without pericardial rub) died
      due to cardiac tamponade on postoperative day 6. Postmortem examination revealed
      hemorrhagic pericarditis with no gross evidence of lead perforation. Pericarditis
      complicates pacemaker implantation in significantly more patients who receive
      active-fixation atrial leads. It may be precipitated byperforation of the atrial
      lead screw through the thin atrial wall. Patients developing postoperative
      pericarditis should befollowed closely due to the risk of cardiac tamponade.

PMID- 12049378
TI  - Pacemaker stored electrograms: teaching us what is really going on in our
      patients.
AB  - Stored electrograms (EGMs), well-known diagnostic tools in implantable
      cardioverter defibrillators, have now been incorporated in pacemakers as well,
      thereby increasing their diagnostic capabilities. The clinician can detect and
      diagnose patient arrhythmias with EGMs and directly validate diagnostic data
      stored by the devices. The appropriateness of detection algorithms can also be
      judged. Initial experiences with pacemaker EGMs reveals their potential to detect
      and diagnose sensing or detection algorithm problems. These so-called "false
      positive" EGMs help to optimize pacemaker programming. Date and time stamp can
      correlate an event to patient symptoms. Recent advances, like onset recordings
      and marker annotation, have further increased the effectiveness of stored EGMs.
      The use of patient-triggered magnet-stored EGMs facilitates diagnostic workups in
      symptomatic pacemaker patients and reveals nondevice related symptoms in a
      considerable number of cases. Stored EGMs in pacemakers will soon be a standard
      diagnostic tool that can illustrate what is really going on in our patients.

PMID- 12049379
TI  - A narrow and two wide QRS complex tachycardias: what are the mechanisms?

PMID- 12049380
TI  - Sunday in the park with George.

PMID- 12049381
TI  - Brugada-like electrocardiographic pattern induced by fever.
AB  - The Brugada syndrome is characterized by a peculiar ST-segment elevation in the
      right precordial leads and the propensity to develop ventricular arrhythmias.
      Mutations in a cardiac sodium channel gene have been linked to this syndrome and
      some experimental data suggest that the dysfunction of the mutated channel can be
      temperature sensitive. This report describes a patient in whom a typical Brugada
      ECG pattern developed in relation to fever but could not be reproduced at normal
      temperature on administration offlecainide. This case suggests that in some
      patients a Brugada-like ECG may only manifest during a febrile state.

PMID- 12049382
TI  - Can radiofrequency current isthmus ablation damage the right coronary artery?
      Histopathological findings following the use of a long (8 mm) tip electrode.
AB  - This report describes the histopathological findings following successful RF
      isthmus ablation for common atrial flutter in a 68-years-old man using a long 8
      mm tip ablation catheter. No acute complication was observed. The patient died 3
      weeks after ablation due to severe heart failure and consecutive pneumonia.
      Lesion width (1.0 and 2.4 cm) and depth (0.4 and 0.8 cm) was measured. The right
      coronary artery showed an intramural hemorrhage adjacent to the side of the
      lesion. However, despite this finding no apparent injury of other layers of the
      coronary artery was detectable.

PMID- 12049383
TI  - Pacemaker contact sensitivity: case report and review of the literature.
AB  - Pacemaker contact sensitivity is a rare condition. Less than 25 reports of
      pacemaker skin reaction have been described over the past 30 years. This report
      describes one patient who developed contact dermatitis after implantation of two
      subsequent pacemakers. The diagnosis was made with skin patch tests that were
      positive to polyurethane 75D and polysulfone beige, two of the pacemaker and
      connector components. Review of the literature and general guidelines for the
      management of this unusual condition is depicted in this report.

PMID- 12049384
TI  - Radiofrequency catheter ablation of an incessant supraventricular tachycardia in
      a premature neonate.
AB  - A 32-week, premature neonate with incessant supraventricular tachycardia and
      hemodynamic compromise who failed to respond to antenatal and postnatal
      antiarrhythmic therapy underwent successful radiofrequency catheter ablation
      (RCA) of a concealed left free-wall accessory pathway when the infant was 4-days
      old and weighed only 1,840 grams. At follow-up performed 60 days after the
      procedure, the infant remained free of any drug, in sinus rhythm, and in normal
      hemodynamic condition.

PMID- 12049385
TI  - Suppression of concealed pulmonary vein bigeminy by atrial pacing in a patient
      with paroxysmal atrial fibrillation.
AB  - Concealed pulmonary vein bigeminy, as a pair of a pulmonary vein spike potential
      within a fragmented far-field atrial electrogram and a premature ectopic
      pulmonary vein spike potential with exit block, was continuously recorded in a
      patient with paroxysmal AF. Atrial pacing suppressed the breakthrough from the
      left atrium to the pulmonary vein, thus preventing the conducted and the
      premature ectopic pulmonary vein potentials. Atrial pacing induced conduction
      block between the left atrium and the arrhythmogenic pulmonary vein might be a
      possible explanation for the prevention of paroxysmal AF by atrial pacing.

PMID- 12049386
TI  - Documentation of acute rise in ventricular capture thresholds associated with
      flecainide acetate.
AB  - Treatment of paroxysmal atrial fibrillation with flecainide acetate resulted in a
      4-fold increase in ventricular capture thresholds. The detailed time course of
      the threshold increase and decrease was documented using the AutoCapture
      algorithm and graphic summary.

PMID- 12049387
TI  - Ozone effects on Sphagnum mosses, carbon dioxide exchange and methane emission in
      boreal peatland microcosms.
AB  - Microcosms of a boreal peatland originating from an oligotrophic fen in Eastern
      Finland were fumigated under four ozone concentrations (0, 50, 100 and 150 ppb
      O3) in laboratory growth chambers during two separate experiments (autumn and
      summer) for 4 and 6 weeks, respectively. Ozone effects on Sphagnum mosses and the
      fluxes of carbon dioxide and methane were evaluated. In both experiments, the
      three Sphagnum species studied showed only a few significant responses to ozone.
      In the autumn experiment, membrane permeability of S. angustifolium, measured as
      conductivity and magnesium leakage, was significantly higher under ozone
      fumigation (P = 0.005 and < 0.001, respectively), and there was a distinct dose
      dependence. S. magellanicum showed no clear responses, either for membrane
      leakage or pigment content. There were no substantial ozone responses in the
      gross photosynthesis or net CO2 exchange during the 6-week-long summer
      experiment, but dark ecosystem respiration was transiently increased by ozone
      concentration of 100 ppb after 14 days of exposure (P < 0.05). Fumigation with
      100 ppb of ozone, however, more than doubled (P < 0.05) methane emission from the
      peatland monoliths. Our results suggest that increasing tropospheric ozone
      concentration may cause substantial changes in the carbon gas cycling of boreal
      peatlands, even though these changes are not closely associated with the changes
      in Sphagnum vegetation.

PMID- 12049388
TI  - An analysis of the combined effects of organic toxicants.
AB  - This paper presents a basic database for the joint actions of 44 binary mixtures
      of various organic toxicants on Escherichia coli. The multiple toxicity behaviors
      observed from the E. coli organisms were analyzed and compared with previous
      works based on the Microtox tests. The two kinds of tests produced quite
      different responses, in terms of the joint action mode and the sum of toxic
      units, to various organic mixtures. However, detailed analyses with the
      considerations of the chemical's mechanisms of toxicity and the slope of
      toxicant's dose-response curve have revealed several general criteria for the
      prediction of combined effects of organic toxicants. First, for both reactive and
      non-reactive toxicants, either additive or less than additive (antagonistic)
      joint actions will be observed for chemicals of the same mechanism of toxicity.
      Second, the mixture of reactive toxicants with different mechanisms is the only
      category of organic mixtures associated with frequent observations of synergism.
      Third, greater-than-additive (synergistic) effects are inherently associated with
      toxicants having flat dose-response curves. Less than additive effects are,
      however, mainly related to a chemical's display steep dose-response curves. Model
      analyses indicate that the observed synergistic effects are due to response
      addition or response multiplication joint actions. Hence, most of the synergistic
      joint actions are non-interactive in nature and are governed by the dose-response
      relationships of individual toxicants.

PMID- 12049389
TI  - Assessment of reference values for mercury in urine: the results of an Italian
      polycentric study.
AB  - The results of a polycentric study to assess the reference values of urinary
      mercury (U-Hg) in four Italian cities are presented. A total of 383 subjects were
      selected on the basis of standardised criteria by a questionnaire on personal
      habits, lifestyle, occupational or non-occupational exposure to Hg, medical
      history, number and area of dental amalgams. U-Hg was determined by hydride
      generation atomic absorption method (HG-AAS), with a detection limit of 0.5
      microg/l and by flow injection (FI) inductively coupled plasma mass spectrometry
      (ICP-MS), with a detection limit of 0.03 microg/l. The median value of U-Hg,
      determined by HG-AAS, was 0.78 microg/g creatinine (0.75 for males and 0.83 for
      females), with 5 degrees and 95 degrees percentiles, respectively, of 0.17 and
      3.66 microg/g creatinine. When determined by FI ICP-MS, the median value was 0.79
      microg/g creatinine (0.77 for males and 0.79 for females) with 5 degrees and 95
      degrees percentiles of, respectively, 0.12 and 5.02 microg/g creatinine. Among
      the independent variables, city of origin, area of dental amalgams, fish intake
      and tobacco smoking significantly influenced the U-Hg levels. The U-Hg reference
      values from this survey are lower than those from other recent investigations,
      probably due to characteristics and selection of the examined individuals and to
      the strict control of pre-analytical and analytical factors of variability.

PMID- 12049390
TI  - An evaluation of biomarkers of reproductive function and potential contaminant
      effects in Florida largemouth bass ( Micropterus salmoidesfloridanus) sampled
      from the St. Johns River.
AB  - The objective of this study was to describe and compare several reproductive
      parameters for Florida largemouth bass (Micropterus salmoides floridanus)
      inhabiting the St. Johns River and exposed to different types and/or degrees of
      contamination. Welaka was selected as the reference site in this study because of
      its low urban and agricultural development, Palatka is in close proximity to a
      paper mill plant, the Green Cove site is influenced by marine shipping activities
      and Julington Creek site receives discharges of domestic wastewater and storm
      water runoff from recreational boating marinas. For this study, bass were sampled
      both prior to (September 1996) and during the spawning season (February 1997). In
      order to characterize chemical exposure, bass livers were analyzed for up to 90
      trace organics and 11 trace metal contaminants. Reproductive parameters measured
      included gonadosomatic index (GSI), histological evaluation of gonads and plasma
      concentrations of vitellogenin (VTG), 17beta-estradiol (E2) and 11
      ketotestosterone (11-KT). In general, the sum of organic chemicals was highest in
      livers from Palatka bass and bass from Green Cove and Julington Creek had higher
      hepatic concentrations of low molecular polycyclic aromatic hydrocarbons and
      polychlorinated biphenyls when compared to fish from Welaka. Metals were more
      variable across sites, with highest mean concentrations found in bass from either
      Julington Creek (Ag, As, Cr, Cu, Zn) or Welaka (Cd, Hg, Pb, Se, Tn). Female bass
      from Palatka and Green Cove had lower concentrations of E2, VTG and lower GSI in
      relation to Welaka. Males from Palatka and Green Cove showed comparable declines
      in 11-KT in relation to males from Julington Creek and GSI were decreased only in
      Palatka males. These results indicate a geographical trend in reproductive
      effects, with changes being most pronounced at the site closest to the paper mill
      (Palatka) and decreasing as the St. Johns River flows downstream. Since
      reproductive alterations were most evident in bass sampled from the site closest
      to the paper mill discharge, it is possible that exposure to these effluents
      might explain at least some of the results reported here. However, the presence
      of reproductive alterations in fish sampled at a considerable distance from the
      mill discharge (Green Cove, 40 km) would suggest exposure to chemicals released
      from sources other than the paper mill plant. It is clear that additional studies
      are needed to evaluate the potential impact of these reproductive changes in
      populations of Florida largemouth bass inhabiting the St. Johns River.

PMID- 12049391
TI  - Identification of atmospheric volatile organic compounds (VOCs), polycyclic
      aromatic hydrocarbons (PAHs) and carbonyl compounds in Hong Kong.
AB  - Volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs) and
      carbonyl compounds are the major organic pollutants in the atmosphere. Emissions
      from motor vehicles have been one of the primary pollution sources in the
      metropolitan area of Hong Kong. A 12-month monitoring program for VOCs, PAHs and
      carbonyl compounds was performed at a roadside urban station at Hong Kong
      Polytechnic University (HKPU) in order to determine the correlations of each
      selected pollutant. The monitoring program ran from 16 April 1999 to 10 April
      2000 for a period of 1 year, and a 2-week winter intensive sampling was carried
      out during January 2000. Traditionally, emission sources are identified from
      organic compounds in air particulates. Since many of the gaseous and particulate
      phases of organic compounds are from the same sources, correlations between the
      major exhausts are to be expected. Therefore, it would be more effective to
      apportion the sources using the combined gaseous and particulate phases of
      organic compounds. Correlations of selected pollutants within two other toxic air
      pollutants (TAPs) monitoring stations in Tsuen Wan (TW) and Central/Western (CW)
      were analyzed. Good correlations were found between pollutants that came from
      vehicle exhaust, especially in intensive sampling periods at HKPU roadside
      station. This was because the washing out effect for particulates during rainy
      days and photochemical degradation during high solar radiation were minimized in
      wintertime.

PMID- 12049392
TI  - Prediction of the bioaccumulation factors and body burden of natural and
      synthetic estrogens in aquatic organisms in the river systems.
AB  - This study undertakes an initial prediction of the bioaccumulation factors and
      body burden of the steroid estrogens, estrone, estradiol, estriol and
      ethinylestradiol in a range of aquatic organisms (plankton, benthic and free
      living invertebrates and fish) in river systems using a food-web model. These
      data are compared to that derived from less complex predictions based on octanol
      water partition coefficient and molecular connectivity index. The model predicted
      that bioaccumulation of steroid estrogens occurred in all organisms, however, the
      values were small, and the maximum and minimum bioaccumulation factors in this
      study were found in the fish at the lowest trophic level with ethinylestradiol
      (332) and the fish at the highest trophic level with estriol (1.8), respectively.
      Moreover, the bioaccumulation factors were sensitive to the metabolic rates of
      the estrogens in the free living organisms, while the concentration of estrogens
      in sediment was a significant factor in determining these values in benthic
      invertebrates. Biomagnification contributed little to the overall
      bioaccumulation, but the importance increased in fish exposed to
      ethinylestradiol. The predicted bioaccumulation factors from the food web model
      were generally smaller than the calculated bioconcentration factors from the
      simpler octanol-water partition coefficient/molecular connectivity index based
      estimates. Compared to literature measured data, the predicted values for fish
      were approximately 1000 times less than the values observed in laboratory tests,
      while for invertebrates, the modeled values were less than two orders of
      magnitude below laboratory results. However, the model predicted a similar
      bioconcentration factor for plankton in relation to experimental data for
      Chlorella vulgaris for estrone and estriol.

PMID- 12049393
TI  - Pb and 206Pb/207Pb isotopic analysis of a tree bark pocket near Sheffield, UK
      recording historical change in airborne pollution during the 20th century.
AB  - A section of tree trunk (beech, Fagus sylvatica) containing a bark pocket
      progressively enclosed at the junction of two branches was collected from a semi
      rural location near Sheffield, UK. According to the annual growth rings, the bark
      pocket formed between ca. 1919 and 1998 (the date of felling). The bark pocket
      was divided into consecutive samples of differing radial depth (and thus age),
      that were analysed by ICP mass spectrometry. The Pb concentration varied from 7
      to 78 mg kg (-1) and the 206Pb/207Pb isotope ratio from 1.11 to 1.15. In
      contrast, the current surface bark contained 46 mg kg(-1) Pb and recorded a
      206Pb/207Pb ratio of 1.11. The changing elemental and isotopic composition of the
      bark pocket recorded historical change in the level and sources of airborne Pb
      pollution. An overall increase in Pb concentration with time was accompanied by a
      progressive reduction in 206Pb/207Pb from ca. 1935 to 1943. Mass balance
      calculations indicated that Pb additives in petrol contributed significantly to
      the rise in concentration, accounting for a maximum of 50% of the total Pb for
      ca. 1986-1998, but that other sources were generally dominant. The highest Pb
      concentrations were recorded from ca. 1951 to 1973, suggesting a high level of
      industrial pollution. A reduction in Pb concentration and reversal of the trend
      in 206Pb/207Pb was observed in the current bark.

PMID- 12049394
TI  - Application of an integrated environmental monitoring system to an incineration
      plant.
AB  - An integrated environmental monitoring system is an innovative approach which
      allows remarkable understanding of impacts due to a contamination source. Here we
      report results from environmental monitoring near a typical Italian incinerator
      plant. By means of mathematical dispersion models, zones of maximum pollutant
      depositions were determined; according to these simulations, a defined monitoring
      network was established. Heavy metals, chosen as environmental indicators, showed
      a wide flux range in gas emissions from the incinerator, over different sampling
      years. In particular, emissions in the year 2000 were marked by high Pb and Cd
      concentrations. Correspondingly, soil samples also exhibited a greater
      concentration of the same metals in 2000, than in previous years. Principal
      component analysis allowed a better visualisation of these similarities, also
      showing an interesting correlation between heavy metals observed both in gas
      emissions and in soil samples. Soil distant from the incinerator was found to be
      less affected by heavy metal contamination. Also atmospheric wet and dry
      depositions indicated a significant dependence on distance from incinerator,
      though extremely variable metal fluxes were registered during different months.
      Finally, vegetation samples, seasonal or evergreen, did not provide evidence of a
      significant heavy metal enrichment, apart from an apparent dependence on
      contamination source distance.

PMID- 12049395
TI  - Acidification sensitivity and critical loads of acid deposition for surface
      waters in China.
AB  - Although decades of severe acid deposition have not resulted in serious surface
      water acidification in China, at present, the risk of some freshwaters becoming
      acidified cannot be neglected. To know more clearly about the possible impact
      acid deposition would have on Chinese surface waters, it is necessary to study
      the sensitivity of those surface waters to acidification and their critical loads
      of acid deposition on a national scale. Here we assess the acidification
      sensitivity of Chinese surface waters using an approach based on geology, soils,
      land use and hydrological conditions. Critical loads of S, N and acidity were
      also evaluated by a first-order acidity balance (FAB) model. Results show that
      most surface waters in China have very high critical loads of S and acidity and
      are not susceptible to acidification. Surface waters can be divided into three
      groups according to both sensitivity classes and critical loads. The few most
      sensitive surface waters are located in the northern part of Daxinganling region,
      with critical loads of S deposition and acidity lower than 2 keq ha(-1) year(-1).
      Surface waters in the northeastern region draining dark brown forest soils and in
      southern China belong to the second class of acidification sensitivity and their
      critical loads of S and acidity are generally between 2 and 15 keq ha(-1) year(
      1), indicating they are not likely to be acidified under any flow conditions.
      Surface waters in other parts of China will not be acidified to any degree, with
      critical loads much higher than 15 keq ha(-1) year(-1). The magnitude and spatial
      distribution pattern of acidification sensitivity have significant similarity to
      the critical loads of S and acidity for Chinese surface waters. Although most
      surface waters are not likely to be acidified, attention should still be paid to
      the possible adverse impact acid deposition would have, especially in
      northeastern China, where the surface waters are the most sensitive, and the
      southern region, where acid pollution is among the most severe in China.

PMID- 12049397
TI  - The sequestration switch: removing industrial CO2 by direct ocean absorption.
AB  - This review paper considers direct injection of industrial CO2 emissions into the
      mid-water oceanic column below 500 m depth. Such a process is a potential
      candidate for switching atmospheric carbon emissions directly to long term
      sequestration, thereby relieving the intermediate atmospheric burden. Given
      sufficient research justification, the argument is that harmful impact in both
      the Atmosphere and the biologically rich upper marine layer could be reduced. The
      paper aims to estimate the role that active intervention, through direct ocean
      CO2 storage, could play and to outline further research and assessment for the
      strategy to be a viable option for climate change mitigation. The attractiveness
      of direct ocean injection lies in its bypassing of the Atmosphere and upper
      marine region, its relative permanence, its practicability using existing
      technologies and its quantification. The difficulties relate to the uncertainty
      of some fundamental scientific issues, such as plume dynamics, lowered pH of the
      exposed waters and associated ecological impact, the significant energy penalty
      associated with the necessary engineering plant and the uncertain costs.
      Moreover, there are considerable uncertainties regarding related international
      marine law. Development of the process would require acceptance of the evidence
      for climate change, strict requirements for large industrial consumers of fossil
      fuel to reduce CO2 emissions into the Atmosphere and scientific evidence for the
      overall beneficial impact of ocean sequestration.

PMID- 12049396
TI  - Seasonal variations of susceptibility to oxidative stress in Adamussium colbecki,
      a key bioindicator species for the Antarctic marine environment.
AB  - The area of free radical biology is of increasing interest for marine organisms
      since the enhanced formation of reactive oxygen species (ROS) is a common pathway
      of toxicity induced by stressful environmental conditions. In polar environments
      responses of the antioxidant system could be useful as an early detection
      biomarkers of unforeseen effects of human activities which are progressively
      increasing in these remote areas. However, the characterization of antioxidant
      defences in appropriate sentinel species is of particular value also in terms of
      a possible adaptation to this extreme environment. The scallop, Adamussium
      colbecki, is a key species for monitoring the Antarctic environment and, besides
      single antioxidants, the total oxyradical scavenging capacity (TOSC) assay has
      been recently used for quantifying the overall ability of this organism to
      neutralize peroxyl radicals (ROO*), hydroxyl radicals (*OH) and peroxynitrite
      (HOONO). The aim of this work was to obtain a better characterization of these
      biological responses which can indicate the occurrence of biological disturbance;
      in this study the total oxyradical scavenging capacity was further analyzed to
      assess the presence of seasonal fluctuations in the susceptibility to oxidative
      stress in this species. The capability to neutralize peroxyl radicals and
      hydroxyl radicals increased at the end of December, while resistance towards
      peroxynitrite did not show any significant variations during the Antarctic
      summer. These results suggest the occurrence of metabolic changes which mainly
      influence intracellular formation of ROO* and *OH, with more limited effects on
      HOONO. Despite the limited time window analyzed, as a typical constraint in
      Antarctic research at Terra Nova Bay, an increased resistance to these specific
      oxyradicals might be related to the period of highest feeding activity, or to
      other intrinsic factors in the animals' physiology such as the phase of
      reproductive cycle.

PMID- 12049398
TI  - Correlation of musty odor and 2-MIB in two drinking water treatment plants in
      South Taiwan.
AB  - Possible odor groups and intensity, and seasonal effects were elucidated in two
      representative water treatment plants (WTPs), Feng-Shen and Gun-Shi, in southern
      Taiwan. The flavor profile analysis (FPA) was employed to determine the odor
      groups for the source water, while a chemical analysis, solid-phase
      microextraction (SPME) coupled with a gas chromatograph and mass spectrometric
      detector (GC/MSD), was used to concentrate and subsequently analyze the
      corresponding water samples. FPA results show that fishy and musty odors were the
      two major odor groups in the source water. Results of chemical analysis showed
      that 2-methyl-isoborneol (2-MIB) was present in the source water. The correlation
      between 2-MIB concentration and the FPA intensity of musty odor was compared with
      the dose-response curve generated in the laboratory by the FPA panelists. The
      experimental data from the two water treatment plants follow the calibration
      curve closely, indicating that the musty odor of the two source waters were most
      likely contributed from 2-MIB. In addition, there is good correlation between
      logarithmic 2-MIB concentration and water temperature, substantiating the
      importance of seasonal effect. Although approximately 40-50% of 2-MIB removal was
      found in the treatment trains for the two WTPs, only an approximately 0.3 FPA
      intensity scale of reduction was expected.

PMID- 12049399
TI  - Biological monitoring of environmental exposure to manganese in blood samples
      from residents of the city of Barcelona, Spain.
AB  - Serum manganese levels were determined in 250 healthy subjects (122 men and 128
      women) living in Barcelona in northeastern Spain. The study was designed to
      assess the reference levels for serum manganese and to investigate its
      relationship to age and sex. The age distribution ranged from 15 to 90 years. The
      assays were performed by means of a graphite furnace atomic absorption
      spectrometry. The geometric mean of serum manganese concentration was 1.1
      microg/l, ranging from 0.3 microg/l to 2.5 microg/l. In almost every case, the
      95th upper percentiles of this element were < 1.8 microg/l. No correlation
      between the concentration of manganese and sex could be established, but in the
      younger population the manganese levels were nearly three times higher than the
      results obtained in the older population.

PMID- 12049400
TI  - Propane and butane emission sources to ambient air of Mexico City metropolitan
      area.
AB  - Samples of volatile organic compounds (VOCs) were collected in a smog chamber in
      order to determine whether automotive exhausts or LP Gas emissions play a greater
      role in the source of propane and butane, which affect ozone formation and other
      pollutants in the ambient air of the Mexico City metropolitan area (MCMA). These
      samples were collected in April 1995 during mornings and evenings. The testing
      methodology used for measuring exhaust emission were FTP or EPA-74 tests, and
      SHED type tests were also conducted in order to evaluate evaporative emissions.
      The finding from analysis of the VOCs collected in the morning demonstrate that
      in the atmosphere, propane concentrations are higher than that of butane but the
      reverse in evaporative and exhaust emissions, with the concentration of propane
      lower than that of butane. Our conclusion is that most of C3 and C4 in the
      ambient air comes from LP gas and not vehicle exhaust or evaporative emission,
      due to the higher levels of propane than butane in its formulation. The analysis
      of VOCs also indicates that although the conversion (in the smog chamber) of
      alkanes is low during the day, due to the high initial concentration, their
      contribution in the reaction mechanism to produce ozone can be appreciable.

PMID- 12049401
TI  - Distribution variations of multi allergens at asthmatic children's homes.
AB  - Increasing asthma prevalence is evident in many countries and childhood asthma
      has also become one of the most common chronic diseases in children. Exposure to
      indoor allergens has been be attributed to a significant increase in asthma
      occurrence. Meanwhile, allergen distribution varies widely among different
      countries. This brief investigation reports the distribution of common indoor
      allergens, such as mite (Dermatophagoides pteronyssinus, Der p 1 and Der p 2),
      cat (Felis domesticus, Fel d 1), and German cockroach allergens (Blattella
      germanica, Bla g 1) at different sites of asthmatic children in Taiwan.
      Approximately 40 asthmatic children's homes participated in this study and the
      cohort was followed prospectively for approximately 6 months, starting in
      December until the following May. Dust samples were collected from each child's
      mattress, and bedroom and living room floors. All samples were analyzed with
      monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Statistical
      difference of Der p 1 concen trations is observed among those on the mattress,
      bedroom and living room floor, except for in May. Seasonal variation in Der p 1
      levels on the mattress and bedroom floor is also significant (P < 0.025 and
      0.001, respectively). Distributional variation seems to be significant for most
      allergens among sites within homes in most seasons. Therefore, if only one sample
      is to be taken, the month of May would be a more ideal choice of study period,
      and detailed sampling across sites appears to be necessary should the true
      environmental exposure of allergens be desired.

PMID- 12049402
TI  - Do powered toothbrushes contaminate toothpaste with metals?
AB  - Replaceable brush units of powered toothbrushes (PTBs) can contain metal parts
      made of nickel and chromium bearing alloy. These alloy ingredients have
      allergenic potential, and may contaminate toothpaste and the mouth during use.
      Here I quantify metals abraded from PTBs. A leading brand of PTB was used in a
      simulated intraoral environment with three leading brand toothpastes, and post
      brushing samples were analysed for iron, chromium, nickel, molybdenum, and
      manganese by certified laboratories using standard methods. Results showed tartar
      control toothpaste abraded most metal, and caused discolouration of toothpaste
      slurry. Discolouration of toothpaste slurry, as a useful indicator of metal
      abrasion, was limited to one toothpaste brand, and not useful across brands.

PMID- 12049403
TI  - Blood lead concentrations and iron deficiency in Canadian aboriginal infants.
AB  - Aboriginal Cree infants living in northern Quebec who were 9 months of age were
      screened for anemia, iron deficiency and elevated blood lead concentrations. Of
      the 314 infants who were eligible to participate, 274 (87.3%) were screened for
      anemia, 186 had blood lead concentration measured and 141 of the latter group had
      iron status determined. The median blood lead concentration was 0.08 micromol/l
      (range 0.01-1.00 micromol/l). The 25, 50 and 75 percentiles for blood lead
      concentration were 0.05, 0.08 and 0.12 micromol/l, respectively. The prevalence
      of elevated blood lead concentrations (> 0.48 micromol/l) was 2.7% (95% Cl 0.36
      5.0). Among infants who had blood lead measured, the prevalence of anemia
      (hemoglobin < 110 g/l) was 25.0% and 7.9% of infants had iron-deficiency anemia
      (hemoglobin < 110 g/l and serum ferritin < 10 microg/l). Anemic infants had a
      higher mean geometric blood lead concentration than did babies without anemia
      (0.11 micromol/l vs. 0.07 micromol/l, P = 0.003). Likewise, infants with iron
      deficiency anemia had a significantly higher mean geometric blood lead
      concentration than infants without iron deficiency anemia (0.16 micromol/l vs.
      0.07 micromol/l, P = 0.001). There was a significant negative correlation between
      blood lead and hemoglobin concentrations (r = -0.203, P = 0.006) and between
      blood lead and serum ferritin concentrations (r = -0.245, P = 0.003). Infants who
      were fed traditional food (fish, fowl and game) did not have a significantly
      different mean geometric blood lead concentration, hemoglobin concentration or
      serum ferritin concentration than infants who did not eat traditional food. Few
      infants (5.3%) ate traditional food daily.

PMID- 12049404
TI  - Determination of selected trace elements in herbs and their infusions.
AB  - The following macro- and microelements were determined in the leaf of peppermint
      (Mentha piperitae folium) and nettle (Urticae folium) (as tea bags) and in their
      infusions: As, Ba, Ca, Cd, Co, Cr, Cu, Fe, I, Li, Mg, Mn, Ni, Pb, Se, Sn, Sr, Ti,
      V and Zn. The determinations were performed using inductively coupled plasma mass
      spectrometry (ICP-MS) and atomic absorption spectrometry (AAS). From all the
      determined microelements the highest content found was that of iron, 244 and 107
      mg/kg in the leaf of peppermint and nettle, respectively. However, the lowest
      content found was that of cobalt, 0.10 and 0.08 mg/kg for the leaf of mint and
      nettle, respectively. The most readily water eluting elements were strontium,
      selenium and iodine, the most difficult ones - barium and iron.

PMID- 12049405
TI  - Human exposure to mercury in San Jorge river basin, Colombia (South America).
AB  - During May-September 1999 human hair samples were collected from the village of
      Caimito, a fishing community of the state of Sucre (Colombia), in the San Jorge
      River basin area, and analyzed for total mercury (t-Hg) by cold vapor atomic
      absorption spectroscopy. T-Hg was measured in both male and female people aged 15
      65 years, whose diet mainly consists of fish collected in nearby marshes. Average
      hair t-Hg concentration in people from Caimito was 4.91 +/- 0.55 microg/g (n =
      94), similar to the value previously detected in fishermen living in the gold
      mining area, 50 km east. Males had similar t-Hg concentrations (4.31 +/- 0.42
      microg/g; n = 56) to females (5.78 +/- 1.21 microg/g; n = 38) and there was no
      difference in t-Hg levels between groups of different age. Mercury content in
      hair was weakly but significantly associated (R = 0.20, P = 0.05) with fish
      consumption.

PMID- 12049406
TI  - Biomarkers and bioassays for detecting dioxin-like compounds in the marine
      environment.
AB  - The presence of toxic chemical contaminants in some marine organisms, including
      those consumed by humans, is well known. Monitoring the levels of such
      contaminants and their geographic and temporal variability is important for
      assessing and maintaining the safety of seafood and the health of the marine
      environment. Chemical analyses are sensitive and specific, but can be expensive
      and provide little information on the actual or potential biological activity of
      the contaminants. Biologically-based assays can be used to indicate the presence
      and potential effects of contaminants in marine animals, and therefore, have
      potential for routine monitoring of the marine environment. Halogenated aromatic
      hydrocarbons (HAHs) such as chlorinated dioxins, dibenzofurans, and biphenyls
      comprise a major group of marine contaminants. The most toxic HAHs (dioxin-like
      compounds) act through an intracellular receptor protein, the aryl hydrocarbon
      receptor, which is present in humans and many, but not all, marine animals. A
      toxic equivalency approach based on an understanding of this mechanism provides
      an integrated measure of the biological potency or activity of HAH mixtures.
      Biomarkers measured in marine animals indicate their exposure to these chemicals
      in vivo. Similarly, in vitro biomarker responses measured in cell culture
      bioassays can be used to assess the concentration of 'dioxin equivalents' in
      extracts of environmental matrices. Here, I have reviewed the types and relative
      sensitivities of mechanistically-based, in vitro bioassays for dioxin-like
      compounds, including assays of receptor-binding, DNA-binding and transcriptional
      activation of native (CYP1A) or reporter (luciferase) genes. Examples of their
      use in environmental monitoring are provided. Cell culture bioassays are rapid
      and inexpensive, and thus have great potential for routine monitoring of marine
      resources, including seafood. Several such assays exist, or are being developed,
      for a variety of marine contaminants in addition to the dioxin-like chemicals. A
      battery of cell culture bioassays might be used to rapidly and sensitively screen
      seafood for the presence of contaminants of concern, including dioxin-like
      compounds as well as other contaminants such as natural toxins, hormonally active
      agents, and heavy metals. Such a battery of mechanism-based, in vitro bioassays
      could be incorporated into monitoring efforts under recently adopted hazard
      analysis and critical control point (HACCP) programs.

PMID- 12049407
TI  - Heavy metal contents (Cd, Cu, Zn) in spiders (Pirata piraticus) living in
      intertidal sediments of the river Scheldt estuary (Belgium) as affected by
      substrate characteristics.
AB  - Metals are transferred into the food web by ground-dwelling organisms, among
      others. This study aimed to identify the most important factors that determine
      the bioavailability of heavy metals to the spider Pirata piraticus living in the
      intertidal sediments of the Scheldt estuary (Flanders, Belgium). At five
      locations, which represent a varying degree of metal contamination and salinity,
      the superficial layer of sediments was characterised for physico-chemical
      properties and heavy metal (Cd, Cu, Zn) content and extractability. Spiders were
      sampled at the same locations and analysed for Cd, Cu and Zn. Higher Cd, Cu and
      Zn contents were found in spiders on sites with lower total metal contents in the
      sediment. These sites were closest to the river mouth and were characterised by a
      higher salinity. Significant, positive correlations were found between the
      chloride content of the sediments and the Cd, Cu and Zn content of P. piraticus.
      Similarly, a strong relationship was observed between the ratio of exchangeable
      Cd and Zn to the total cation exchange capacity and the contents of these
      elements in P. piraticus. These field data indicated that salinity, cation
      exchange capacity and exchangeable metal contents were of most importance in
      determining bioavailability of heavy metals in these intertidal sediments.

PMID- 12049408
TI  - Prediction of the effects of soil-based countermeasures on soil solution
      chemistry of soils contaminated with radiocesium using the hydrogeochemical code
      PHREEQC.
AB  - For agriculturally used areas, which are contaminated by the debris from a
      nuclear accident, the use of chemical amendmends (e.g. potassium chloride and
      lime) is among the most common soil-based countermeasures. These countermeasures
      are intended to reduce the plant uptake of radionuclides (mainly 137Cs and 90Sr)
      by competitive inhibition by chemically similar ions. So far, the impacts of
      countermeasures on soil solution composition - and thus, their effectiveness -
      have almost exclusively been established experimentally, since they depend on
      mineral composition and chemical characteristics of the soil affected. In this
      study, which focuses on caesium contamination, the well-established code PHREEQC
      was used as a geochemical model to calculate the changes in the ionic
      compositions of soil solutions, which result from the application of potassium or
      ammonium in batch equilibrium experiments. The simple ion exchange model used by
      PHREEQC was improved by taking into account selective sorption of Cs+, NH4+ and
      K+ by clay minerals. Calculations were performed with three different initial
      soil solution compositions, corresponding to particular soil types (loam, sand,
      peat). For loamy and sandy soils, our calculational results agree well with
      experimental data reported by Nisbet (Effectiveness of soil-based countermeasures
      six months and one year after contamination of five diverse soil types with
      caesium-134 and strontium-90. Contract Report NRPB-M546, National Radiation
      Protection Board, Chilton, 1995.). For peat, discrepancies were found indicating
      that for organic soils a reliable set of exchange constants of the relevant
      cations still has to be determined experimentally. For cesium, however, these
      discrepancies almost disappeared if selective sites were assumed to be
      inaccessible. Additionally, results of sensitivity analyses are presented by
      which the influence of the main soil parameters on Cs+ concentrations in solution
      after soil treatment has been systematically studied. It is shown that
      calculating the impacts of soil-based chemical countermeasures on soil solution
      chemistry using geochemical codes such as PHREEQC offers an attractive
      alternative to establishing these impacts by often time-consuming and site
      specific experiments.

PMID- 12049409
TI  - Electrokinetic soil remediation--critical overview.
AB  - In recent years, there has been increasing interest in finding new and innovative
      solutions for the efficient removal of contaminants from soils to solve
      groundwater, as well as soil, pollution. The objective of this review is to
      examine several alternative soil-remediating technologies, with respect to heavy
      metal remediation, pointing out their strengths and drawbacks and placing an
      emphasis on electrokinetic soil remediation technology. In addition, the review
      presents detailed theoretical aspects, design and operational considerations of
      electrokinetic soil-remediation variables, which are most important in efficient
      process application, as well as the advantages over other technologies and
      obstacles to overcome. The review discusses possibilities of removing selected
      heavy metal contaminants from clay and sandy soils, both saturated and
      unsaturated. It also gives selected efficiency rates for heavy metal removal, the
      dependence of these rates on soil variables, and operational conditions, as well
      as a cost-benefit analysis. Finally, several emerging in situ electrokinetic soil
      remediation technologies, such as Lasagna, Elektro-Klean, electrobioremediation,
      etc., are reviewed, and their advantages, disadvantages and possibilities in full
      scale commercial applications are examined.

PMID- 12049410
TI  - Characterization and immunolocalization of a main proteinaceous component of the
      cell wall of the protozoan parasite Perkinsus atlanticus.
AB  - Described in the present study is a major component of the cell wall of 2 of the
      most pathogenic parasites of molluscs, Perkinsus atlanticus and P. marinus. The
      component is a high molecular weight protein (233 kDa), which we have named PWP-1
      (for Perkinsus wall protein-1). Western blots, using a polyclonal serum generated
      against purified PWP-1 from P. atlanticus, revealed that this protein is
      expressed by all walled developmental stages of this protozoon. By means of
      immunogold electron microscopy, labelling for PWP-1 was strong and specifically
      associated with the cell wall. The label density and distribution pattern was
      quite different between trophozoites and prezoosporangia. With regard to the
      structural organization of this protein, PWP-1 is disulphide-linked to other cell
      wall components and released from the cell wall only following treatment with a
      sulphydryl agent. We also report that PWP-1 is a trypsin-resistant protein, both
      in its native and heat-denatured conformation. In addition, results from the N
      terminal microsequence of this protein allow us to define PWP-1 as a novel cell
      wall protein. Overall, our findings strongly suggest that PWP-1 plays a key role
      in the organization of the cell wall of these protozoa, promoting their survival.

PMID- 12049411
TI  - Infection and transformation of dendritic cells from bovine afferent lymph by
      Theileria annulata.
AB  - Following incubation with sporozoites of the protozoan parasite Theileria
      annulata, dendritic cells (DC), extracted from bovine afferent lymph, became
      infected and transformed into large, rounded, continuously proliferating cell
      lines. Phenotypic analysis of the transformed cells by immunostaining and flow
      cytometry revealed that they expressed MHC class I and II antigens, the myeloid
      marker MyD (SIRP alpha) and the bovine WC6 (workshop cluster 6) molecule.
      Transformed DC cell lines differed from those produced from infection of
      macrophages and B cells in that some lines expressed CD21 and a proportion of
      cells continued to express the antigen stained by the mAb CC81, a marker which
      defines a subpopulation of DC in afferent lymph. Both of the main populations of
      DC that have been identified in bovine afferent lymph appeared to be equally
      permissive for infection and transformation with T. annulata. These findings
      raise the possibility that the transformed proliferating cells characteristic of
      in vivo infections could be derived from DC as well as macrophages. This could
      have consequences for understanding the pathogenesis of the disease and for
      developing methods to manipulate immune responses to eliminate the parasite.

PMID- 12049412
TI  - The role of promastigote secretory gel in the origin and transmission of the
      infective stage of Leishmania mexicana by the sandfly Lutzomyia longipalpis.
AB  - Transmission of leishmaniasis is effected by a specific developmental stage, the
      metacyclic promastigote. The precursors of metacyclic promastigotes were a
      distinct subpopulation of parasites, identified for the first time as a new stage
      in the life-cycle and named leptomonad promastigotes. Microdissection of infected
      sandflies into 4 midgut regions and foregut allowed precursor-product
      relationships to be established for amastigote-procyclic promastigote, procyclic
      nectomonad promastigote, nectomonad-leptomonad promastigote and leptomonad
      metacyclic promastigote developmental switches. Metacyclic promastigotes occurred
      mainly in the thoracic midgut and cardia, coincident with the accumulation of a
      promastigote secretory gel (PSG) plug in these anterior regions. The gel-like
      plug was isolated from flies with mature infections and found to contain
      predominantly leptomonad promastigotes. The PSG plug also contained the majority
      (75%) of the total metacyclic promastigote population in the sandflies, which
      were concentrated at the anterior pole. The PSG plug was found to be the main
      site of metacyclogenesis, and acted as a reservoir of leptomonad promastigotes
      from which metacyclic forms differentiated and migrated forward to promote the
      infective potential of the fly. The PSG plug occluded and distorted the midgut,
      forcing the stomodeal valve open and affecting the feeding success of the
      sandflies, such that they experienced difficulty in taking a full meal.
      Collectively, these data support the role of the PSG in the transmission of
      leishmaniasis, by conditioning the midgut environment for metacyclogenesis and
      altering the feeding ability of infected sandflies.

PMID- 12049413
TI  - Regulation of anti-filarial IgE by infection pressure.
AB  - In lymphatic filariasis, specific IgG4 responses to the parasite and their
      relationship with infection have been studied extensively, but only a few studies
      have concentrated on anti-filarial and total IgE. Here we have investigated the
      role of filarial infection pressure on production of IgE by considering length of
      exposure (age), filarial endemicity and parasitological status. Antibody levels
      were determined in 366 individuals, who were resident in 3 villages in South
      Sulawesi, Indonesia, with varying degrees of filarial transmission intensity, as
      indicated by the prevalence of Brugia malayi microfilaraemia (0.7%, 9% and 32%,
      respectively). Anti-filarial IgE levels were significantly lower in the low
      transmission village than in the areas with intermediate and high filarial
      transmission; however, in the latter village a remarkable suppression of specific
      IgE was found. Microfilaria-positive individuals showed elevated levels of total
      IgE, but suppression of specific IgE, which has been reported before. Taken
      together, these observations suggest that 2 opposing mechanisms regulate anti
      parasite IgE expression: increasing experience of filarial infection stimulates
      specific IgE, but antibody levels become specifically suppressed when
      microfilariae or adult worms develop. Using a simple mathematical model, we
      illustrate how anti-filarial IgE increases with parasite antigen up to a
      threshold level, but levels off and becomes down-regulated after the threshold is
      exceeded.

PMID- 12049414
TI  - The parasite-induced surfacing behaviour in the cockle Austrovenus stutchburyi: a
      test of an alternative hypothesis and identification of potential mechanisms.
AB  - The New Zealand cockle Austrovenus stutchburyi, whose foot is commonly infected
      by the digenean trematode Curtuteria australis (Echinostomatidae), is often found
      heavily infected and unable to burrow on the sediment surface of tidal flats.
      This has been interpreted as a Curtuteria-manipulation with the purpose of
      increasing the transmission of the parasite to shorebirds acting as final hosts.
      Using a field-experimental approach the alternative hypothesis was tested, that
      surface-dwelling cockles, caught on the surface for other reasons than parasites,
      accumulate larval C. australis at a higher rate than buried cockles. During the 3
      month experiment, larval trematodes accumulated with a rate of approximately 0.5
      metacercariae/day in both surface and buried cockles. The result strengthens the
      manipulation hypothesis indirectly by rejecting the alternative hypothesis. The
      metacercariae were unevenly distributed along the cockle-foot, with about 4 times
      as many cysts being found in the tip than in either the mid or hind part of the
      foot. In light of existing knowledge of the burrowing behaviour and apparatus in
      bivalves, and a negative relationship between foot mobility and infection
      intensity, it is suggested that C. australis manipulates its host through a
      mechanical obstruction of foot muscles and the dynamic hydrostatic skeleton, both
      necessary for successful burrowing.

PMID- 12049415
TI  - The effect of an experimental infection of the nematode Heterakis gallinarum on
      hand-reared grey partridges Perdix perdix.
AB  - We compared 26 hand-reared grey partridges given an experimental infection of the
      caecal nematode Heterakis gallinarum with 26 uninfected ones. Under laboratory
      conditions after 91 days, there were no measurable clinical effects of the
      infection. We found no effect of treatment on the amount of food eaten or on
      caecal dropping production. However, treated birds, in particular females,
      developed slightly lower body mass (around 2%) compared to the controls. At post
      mortem examination, we found a positive relationship between breast muscle mass
      and the number of worms collected from the caeca of treated birds. Treated birds
      with no worms when examined had smaller breast muscle mass (4.6%) compared to the
      uninfected control birds. These results are largely different to those found in a
      similar study that documented significant negative impacts on most of these
      factors in 8 infected birds compared to 6 controls. Its findings were used in a
      published model to support a hypothesis that H. gallinarum maintained in the
      environment by common pheasants, the primary host for this worm, could negatively
      affect wild grey partridge productivity and survival. In the same model our data
      would not support this hypothesis. Possible explanations for the different
      results from the 2 experiments are discussed. Together they suggest that only in
      certain, as yet unidentified circumstances, could experimental H. gallinarum
      infections have deleterious effects on hand-reared grey partridges.

PMID- 12049416
TI  - Intra- and interspecific density-dependent effects on growth in helminth
      parasites of the cormorant, Phalacrocorax carbo sinensis.
AB  - The action of intra- and interspecific competition, mediated by density-dependent
      effects on growth, was investigated among the 3 helminth species found in the
      alimentary tract of 104 cormorants, Phalacrocorax carbo sinensis. Intraspecific
      density-dependent effects on worm sizes were observed in the abundant nematode
      Contracaecum rudolphii, as shown by a negative correlation between mean worm size
      and intensity of infection. Higher intensities of infection by C. rudolphii were
      also associated with more variable worm sizes in the nematode Syncuaria squamata,
      suggesting a one-sided and density-dependent interspecific effect. There was also
      clear evidence of some form of negative interaction between the nematode S.
      squamata and the acanthocephalan Southwellina hispida from two fronts. First,
      there was a strong negative correlation between the intensities of infection of
      the 2 species across hosts. Second, sizes of worms of 1 species became more
      variable as the number of worms of the other species per host increased, and vice
      versa. This interspecific density-dependent effect on growth was thus apparently
      symmetrical. We also found evidence that worm size is a predictor of egg output
      in the 3 helminth species, indicating that intra- and interspecific density
      dependent effects on growth can affect population dynamics in these worms. These
      results illustrate the complex nature of density dependence in helminth growth,
      and how its effects can act both within and among species.

PMID- 12049417
TI  - The genetic control of IgA activity against Teladorsagia circumcincta and its
      association with parasite resistance in naturally infected sheep.
AB  - Previous studies in deliberately infected sheep have shown an association between
      IgA activity against 4th-stage larvae of Teladorsagia circumcincta and parasite
      growth, development and fecundity. The purpose of this research was to determine
      if these results could be confirmed in naturally infected sheep and to explore
      the hypothesis that plasma IgA activity could help to identify resistant lambs
      with shorter adult nematodes. Plasma IgA activity was skewed with most animals
      having relatively low levels of IgA activity. Plasma IgA activity was repeatable
      and highly heritable. Animals with increased IgA activity had lower egg counts
      and shorter adult female T. circumcincta. Therefore, under conditions of natural
      parasite challenge, plasma IgA activity may help to identify lambs resistant to
      T. circumcincta.

PMID- 12049418
TI  - Eosinophilia as a marker of resistance to Teladorsagia circumcincta in Scottish
      Blackface lambs.
AB  - Faecal egg counts and peripheral blood eosinophil counts were taken from Scottish
      Blackface lambs following natural, predominantly Teladorsagia circumcincta
      infection. Peripheral eosinophil concentrations were higher in animals with lower
      egg counts but only in lambs that were at least 3 months of age. The reduced egg
      counts were due to reduced fecundity of T. circumcincta; there was no association
      with the number of adult T. circumcincta. Associations with the number of
      parasites from other species of gastrointestinal nematodes appeared to be neutral
      or favourable. Estimated heritabilities for eosinophil concentrations in 4- and 5
      month-old lambs were 0.48 +/- 0.16 and 0.43 +/- 0.17, respectively. Therefore,
      under defined circumstances, eosinophil concentrations may be a useful indicator
      of resistance to predominantly T. circumcincta infection.

PMID- 12049419
TI  - Impact of protein energy malnutrition on Trichuris suis infection in pigs
      concomitantly infected with Ascaris suum.
AB  - The objective of this experiment was to investigate a possible interaction
      between protein and energy malnutrition (PEM) and intestinal nematode infections.
      We report on a 3 x 2 factorial study in which pigs were fed either a low protein
      energy (LPE), low protein (LP) or a normal protein energy (NPE) diet, and 6 weeks
      later inoculated with Trichuris suis (4000 infective eggs). Secondarily, in order
      to obtain a polyparasitic status, pigs were concomitantly inoculated with Ascaris
      suum (600 infective eggs). The number of T. suis-infected pigs was higher in LP
      pigs compared with NPE pigs (100 versus 58%; P = 0.037), although the differences
      in median T. suis worm burdens between groups at necropsy 10 weeks post-infection
      (p.i.) (LPE: 795; LP: 835; NPE: 48 worms; P = 0.33) were not significant.
      Interestingly, only T. suis in NPE were highly aggregated (k = 0.44), in contrast
      to a more uniform distribution among pigs in LPE (k = 1.43) and LP (k = 1.55)
      i.e. the majority of pigs harboured moderate worm burdens in LPE and LP, while
      most pigs had few or no worms in NPE. Further, T. suis worms in the LPE and LP
      groups were decreased in length (mean: LPE: 23.5 mm; LP: 24.3 mm; NPE: 29.4 mm; P
      = 0.004). The pre-patency period of T. suis was also extended in the LPE and LP
      groups, as reflected by lower faecal egg output at week 6 (P = 0.048) and/or 7
      p.i. (P = 0.007). More A. suum worms were recovered from LP compared with the NPE
      group (mean: 5.4 versus 0.6; P = 0.040); this was accompanied by a higher faecal
      egg output in the former (P = 0.004). The low protein diets resulted in lower pig
      body weight gains, serum albumin, haemoglobin and packed cell volume (PCV) levels
      as well as diminished peripheral eosinophil counts. Infection significantly
      altered these parameters in the low protein groups, i.e. the pathophysiological
      consequences of infection were more severe in the PEM pigs. These results
      demonstrate that reduced protein in the diet leads to malnourishment of both the
      host pigs and T. suis, and compromises the pig's ability to resist infection by
      T. suis and A. suum.

PMID- 12049420
TI  - Association of point-of-purchase tobacco advertising and promotions with choice
      of usual brand among teenage smokers.
AB  - The objective is to determine the relationship between brand-specific advertising
      and promotions in convenience stores for Marlboro and Camel cigarettes and choice
      of usual brand among school students. A cross-sectional survey was designed that
      merged records of store tobacco advertising and promotions. The survey was
      administered to 3,890 U.S. high school smokers with a usual brand, matched to 196
      convenience stores. Choice of Marlboro as a usual brand was associated with
      presence of a Marlboro gift with purchase (p <.001) and a greater brand share of
      interior (p = .05) and exterior (p = .05) advertising voice for Marlboro. Choice
      of Camel as a usual brand was associated with a greater share of interior
      advertising voice for Camel (p <.001) but was unrelated to a Camel gift with
      purchase promotions (p > .05) and negatively associated with a greater share of
      exterior advertising voice for Camel (p < .001). The results are consistent with
      the notion that Marlboro-specific advertising and promotions may influence choice
      of Marlboro as a usual brand to smoke among teens, but resultsfor Camel are mixed
      and inconclusive. Further research is required to confirm and extend these
      findings.

PMID- 12049421
TI  - Exploring antismoking ads: appeals, themes, and consequences.
AB  - In this study we seek a descriptive understanding of antismoking television
      advertising in light of the problem cigarette consumption poses for society
      today. We establish relationships between ad characteristics and whether ads have
      a youth or adult orientation, based on a content analysis of 197 antismoking
      television advertisements produced between 1991 and 1999. The study finds that
      youth-oriented ads have youth characters, sociability, and humor as common
      appeals, and social and short-term consequences. In contrast, adult-oriented ads
      relied on fear appeals and long-term, health-related consequences.

PMID- 12049423
TI  - Antismoking advertising: figuring out what works.

PMID- 12049422
TI  - High school journalists' perspectives on tobacco.
AB  - How issues are covered in the media is an important factor in influencing public
      opinion, policy, and individual behavior. During the 1990s, the tobacco control
      movement developed a youth focus, prompted by research showing that most adult
      smokers begin tobacco use as teens. However, concern has been raised that this
      youth focus has derailed the overall goal of achieving a smoke-free society.
      Numerous studies have analyzed tobacco coverage and documented the impacts of
      media messages on youth. To learn how tobacco is covered in a medium primarily
      produced by and for youth, we conducted an analysis of tobacco coverage in high
      school newspapers. High school newspapers, like other media, communicate social
      messages through both content selection and framing. We surveyed a national
      sample of high school journalists and conducted content and frames analyses of
      tobacco articles (n = 257) from their publications. The most commonly used frame
      was "kids" (46%), followed by "killer" (31%), "nonsmokers' rights" (10%), and
      "choice" (5%). "Kids"-framed articles were less likely to mention health effects
      and less likely to be favorable toward tobacco control policies than "killer"
      framed articles. In addition, many "kids" articles included "resistance
      statements" congruent with viewing tobacco use as rebellion and/or independence.
      Lack of a consistently used frame has been identified as a barrier to effective
      tobacco control. Tobacco control media advocacy should focus on developing frames
      that are easily communicated, consistently used, and compatible with the
      developmental tasks of adolescents. Youth journalists should also be included in
      media advocacy efforts.

PMID- 12049424
TI  - Public health at risk: media and political malpractice.

PMID- 12049426
TI  - Counting coin and paper currency: were reported health problems related to the
      work environment?

PMID- 12049425
TI  - Receptivity to protobacco media and its impact on cigarette smoking among ethnic
      minority youth in California.
AB  - Adolescents from different ethnic groups show different cigarette smoking
      prevalence rates, suggesting potential differences in receptivity to and
      influences from protobacco media. Understanding these differences will be helpful
      in tailoring smoking prevention and cessation programs for diverse adolescent
      populations in the United States. Data from cross-sectional surveys of 20,332
      randomly sampled California boys and girls, 12-17 years of age, were analyzed.
      Results indicate that receptivity to protobacco media was lower among African
      Americans, Asian Americans, and Hispanics than among White youth. There was a
      consistent dose-response relationship between receptivity to protobacco media and
      30-day cigarette smoking across ethnic groups. Having a cigarette brand
      preference was associated with the highest risk for cigarette smoking, having a
      favorite tobacco ad showed the lowest risk, while having received or being
      willing to use tobacco promotional items was associated with a moderate risk.
      After controlling for 13 covariates, the odds ratio for receptivity to protobacco
      media and 30-day cigarette smoking was significant for Whites (RR = 1.38, p <
      0.01) and Hispanics (RR = 1.46, p < 0.01), but not for African American (RR =
      1.05, p > 0.05) and Asian American (RR = 1.17, p > 0.05) youth. African American,
      Asian American, and Hispanic adolescents have a lower level of receptivity to
      protobacco media than do Whites. The association between media receptivity and 30
      day cigarette smoking exists for all four ethnic groups without controlling for
      other smoking predictor variables, but only for Hispanics and Whites when other
      variables are controlled. Protecting adolescents from protobacco advertising
      influences is an important element in tobacco control among ethnic minority
      youth.

PMID- 12049427
TI  - Traffic hazards to firefighters while working along roadways.

PMID- 12049428
TI  - Occupational monitoring of particulate diesel exhaust by NIOSH method 5040.
AB  - NMAM 5040 is a particulate carbon method based on a thermal-optical analysis
      technique. The method was evaluated and published as a method for monitoring
      occupational exposures to particulate diesel exhaust, but it is applicable to
      particulate carbon aerosols in general, and has been routinely used in both
      occupational and environmental settings. Both organic and elemental carbon are
      determined, but EC is a more selective measure of workplace diesel exposure. In
      previous studies, good agreement between TC results obtained by different methods
      has been achieved, but the OC-EC results for different methods have been quite
      variable. Although a reference material is not currently available to test the
      accuracy of different methods, previous studies indicate that purely thermal
      methods are subject to positive bias from organic materials that char. Charring
      and inadequate removal of refractory OC components during the nonoxidative mode
      (typically 550 degrees C in nitrogen) likely explain the positive bias of thermal
      methods, as well as the large variability across methods. These interferences may
      be negligible in some cases (e.g., samples from mines), but they present
      significant biases in others (e.g., urban air samples, samples containing wood or
      cigarette smokes). Good interlaboratory agreement was obtained in a round robin
      comparison between six laboratories that used NMAM 5040, which was not the case
      with purely thermal methods. Good agreement has also been seen in smaller-scale
      comparisons conducted for quality assurance purposes. Until a suitable reference
      material becomes available, such comparisons are recommended as part of a
      laboratory's QA procedures. At present, five commercial laboratories (4 in the
      United States and 1 in Canada) perform the 5040 analysis, and over 40 instruments
      are in use globally for environmental and occupational monitoring.

PMID- 12049429
TI  - I-BEAM--an innovative building air quality software tool.

PMID- 12049430
TI  - Total dust, respirable dust, and microflora toxin concentrations in Colorado corn
      storage facilities.
AB  - To aid in the process of characterizing corn dust exposures on farms and in
      elevators in northeastern Colorado, several parameters were examined. Total dust
      and respirable dust samples were collected and evaluated. Potentially dangerous
      dust components evaluated were respirable silica, endotoxin, and mycotoxin
      levels. Many of the total dust samples (58%) would have exceeded 8-hour time
      weighted average (TWA) had sampling been conducted for 8 hours; on farms the
      operation takes between two and four hours. The same statement may be made for
      respirable dust samples collected for this project. Nearly 33 percent of the
      respirable dust samples collected would have exceeded the Occupational Safety and
      Health Administration (OSHA) TWA had sampling been conducted over an 8-hour
      period. Respirable silica standards were exceeded at 25 percent of the sampling
      locations. Presence of mycotoxins at all sites was confirmed by the use of ELISA
      kits. The most significant finding of this study was high levels of endotoxin at
      several of the sampling sites. Eighty-five percent of the sampling locations had
      endotoxin levels above 500 EU/m3. One location, Farm 4, had endotoxin levels of
      above 1.7 million EU/m3.

PMID- 12049431
TI  - A comparison of two surface sample collection devices for use in polymerase chain
      reaction based detection of Pneumocystis carinii in house dust.
AB  - A polymerase chain reaction assay was optimized to detect P. carinii cysts in
      composite dust samples. The optimal assay was capable of detecting as few as
      10(3) P. carinii cysts in 50 mg of dust. Two dust collection devices were
      evaluated for efficiency and precision of collection of bulk dust and
      compatibility with the optimized PCR protocol for P. carinii DNA detection. A
      handheld vacuum cleaner equipped with a high-retention bag was found to be
      superior to a 37-mm filter cassette attached to an electrically powered vacuum
      pump in terms of dust collection efficiency (87% [n = 37] versus 81% [n = 35]),
      although the precision of the two devices as assessed by the standard deviation
      was similar (6.2% versus 6.3%). However, the vacuum cleaner method was not as
      compatible with the PCR-based detection assay as the filter cassette method. The
      filter cassette appears to be a better device for use in conjunction with PCR
      based detection of P. carinii DNA in bulk dust samples from both smooth and
      carpeted surfaces.

PMID- 12049432
TI  - An evaluation of compliance with occupational exposure limits for crystalline
      silica (quartz) in ten Georgia granite sheds.
AB  - Since the 1920s, industrial hygiene studies have documented granite shed workers'
      exposures to crystalline silica, and the data from these studies have contributed
      to a better understanding of the relationship between silica exposures and
      adverse health effects, such as silicosis. The majority of these studies were
      conducted in the Barre, Vermont, granite sheds. However, a second major granite
      processing region is located in Elberton, Georgia, where approximately 1800
      workers are employed in 150 granite sheds and 45 quarries. The current study
      reports the exposures of 40 workers in 10 granite sheds in Elberton, Georgia. The
      arithmetic mean exposure to silica for all monitored employees was 0.052 mg/m3.
      Employees were classified into one of seven job task groups. The job task group
      with the greatest exposure was the top polish group, which had a mean exposure of
      0.085 mg/m3. Among the top polish workers, the greatest percentage of exposures
      above the Occupational Safety and Health Administration's permissible exposure
      limit (OSHA PEL) occurred among the workers who used dry grinders. Wet methods
      were effective in reducing these exposures to below the OSHA PEL. The mean
      exposure of Elberton granite shed workers was less than the OSHA PEL, but was not
      below the threshold limit value of the American Conference of Industrial
      Hygienists (ACGIH TLV), which was lowered in the year 2000 to 0.05 mg/m3. The
      Elberton granite shed workers provide a valuable cohort for research on the
      effects of exposure to crystalline silica at levels between the ACGIH TLV and the
      OSHA PEL. They are a relatively permanent worker population, are concentrated
      geographically, and have a quantitatively documented exposure to crystalline
      silica over the past twenty years.

PMID- 12049433
TI  - Volatile metabolites produced by three strains of Stachybotrys chartarum
      cultivated on rice and gypsum board.
AB  - Stachybotrys chartarum (atra) is a toxigenic fungus frequently found in water
      damaged buildings. Although microbial volatile organic compounds (MVOCs) produced
      by Aspergillus, Penicillium, and other fungi have been investigated extensively,
      little information exists on what MVOCs can be produced by S. chartarum. In this
      study, three strains of S. chartarum isolated from water-damaged residential
      homes in Cleveland, Ohio, were cultivated on rice and gypsum board. Air samples
      were collected after one, two, three, four, and six weeks of cultivation using
      Tenax TA tubes. Unique MVOCs were determined and other alcohols, ketones, and
      terpenes were also investigated using gas chromatography/mass spectrometry after
      thermal desorption from the sampling tube. Four unique MVOCs, 1-butanol, 3-methyl
      1-butanol, 3-methyl-2-butanol, and thujopsene, were detected on rice cultures,
      and only one of them (1-butanol) was detected on gypsum board cultures. For a
      given strain, volatiles were considerably different with different cultivation
      media. Concentration profiles of the volatile compounds varied among compounds;
      however, each compound exhibited corresponding concentration trends between the
      strains. In comparison with our previous studies of five Aspergillus species on
      gypsum board under the same experimental conditions, fewer unique MVOCs were
      produced by S. chartarum, and they were quite different. It thus may be possible
      to use marker-unique MVOCs as a fingerprint to distinguish fungi in indoor
      environments once enough information becomes available. Our findings also
      indicate that volatiles produced by S. chartarum may represent a relatively small
      fraction of the total volatiles present in problem buildings where Aspergillus
      spp., Penicillium spp., and other fungi usually coexist.

PMID- 12049434
TI  - Airborne exposure to heavy metals and total particulate during abrasive blasting
      using copper slag abrasive.
AB  - This research investigates occupational exposure to metal and total particulate
      aerosols during abrasive blasting operations using one substitute abrasive,
      copper slag. Airborne exposures to metal (As, Be, Pb, Cr, Cd, V, and Ti) and
      total particulate aerosols from two copper slag sources are evaluated by the
      collection and analysis of personal breathing zone samples during abrasive
      blasting operations in both indoor and outdoor settings. Results from this
      research indicate that abrasive blasting operations using copper slag abrasive
      can generate, in a relatively short time, total particulate, lead, arsenic, and
      chromium exposures that exceed permissible exposure limits (PELs) set by the
      Occupational Safety and Health Administration (OSHA). Results also show
      statistically significant differences in exposure concentrations between slag
      sources. A correlation between total particulate concentrations and metal
      concentrations is indicated in both slag sources and in both indoor and outdoor
      settings. Results of this research allow occupational health and safety
      professionals to make a more informed determination of the degree of health risk
      posed to workers during abrasive blasting operations using commercially obtained
      copper slag abrasive.

PMID- 12049435
TI  - A qualitative evaluation of questions and responses from five occupational
      questionnaires developed to assess exposures.
AB  - Questionnaires are increasingly being used in the workplace to assess exposures
      to chemicals and other agents. Although the literature contains much information
      on questionnaire design in general, little information is available on the
      challenges related to questionnaires applied to the occupational setting.
      Questionnaires on dry cleaning workers, nurses, farmers, car mechanics, and truck
      drivers were administered to a total of 25 people currently performing one of
      these jobs. After asking each question, the interviewer probed to identify the
      difficulties the respondents had in answering the questions. Overall, the
      respondents were able to answer the questions. Problems were found, however, with
      particular questions that reduced the effectiveness of the questionnaire. These
      included the use of unclear terms, questions open to multiple interpretations,
      difficult computational requirements (e.g., asking for averages for highly
      variable tasks), ineffective transitions between topics, and overlapping response
      categories. This type of testing is a crucial part of questionnaire development
      and can be used to effectively identify potential problems with questions and,
      therefore, improve them to enhance collection of higher-quality data for
      assessments of occupational exposures.

PMID- 12049436
TI  - Kava-induced fulminant hepatic failure.

PMID- 12049437
TI  - Valproic acid and risperidone.

PMID- 12049438
TI  - Gabapentin in complicated school refusal.

PMID- 12049439
TI  - Ten-year review of rating scales. II: Scales for internalizing disorders.
AB  - OBJECTIVE: This article, the second in the Journal's series of 10-year updates on
      rating scales, summarizes scales assessing internalizing disorders. METHOD: The
      authors sampled articles on mood and anxiety disorders over the past 25 years,
      selected scales with multiple citations over many years, and reviewed their
      properties. Those with adequate psychometric properties, plus continued wide
      literature citations or a current special niche, are presented here. RESULTS:
      Rating scales for depression were developed and/or examined in the 1980s. Despite
      generally strong properties, they lack clear construct validity. Most have parent
      report forms that broaden their suitability with youths. Anxiety scales were
      developed bimodally. Those developed in the 1960s to 1970s were downward
      modifications of adult scales. They have been criticized for unclear constructs
      and unsuitability for youths. Newer scales developed in the 1990s have addressed
      these problems and have parent-report forms. However, their utility is still
      being determined. CONCLUSIONS: Rating scales can reliably, validly, and
      efficiently measure youths' internalizing psychopathology. They have great
      utility in research, treatment planning, and accountability in practice. However,
      the user must define the goals of measurement, consider the construct the scale
      measures, and use the scale within its defined capabilities. The use of more than
      one scale for a task is recommended.

PMID- 12049440
TI  - Anxiety, affect, and activity in teenagers: monitoring daily life with electronic
      diaries.
AB  - OBJECTIVE: The everyday experiences of a community sample of adolescents
      differing in anxiety level were compared by means of electronic diaries. METHOD:
      One hundred fifty-five ninth-grade adolescents completed electronic diaries every
      30 minutes for two 4-day intervals, reporting their moods, activities, social
      settings, dietary intake, smoking, and alcohol use. Teenagers were stratified
      into low-, middle-, or high-anxiety groups on the basis of diary ratings and,
      separately, questionnaire scores. RESULTS: High-anxiety teenagers, compared with
      low-anxiety teenagers, expressed higher levels not only of anxiety and stress but
      also of anger, sadness, and fatigue, along with lower levels of happiness and
      well-being. They reported fewer conversations and less recreational activity
      relative to achievement-oriented pursuits, stronger eating and smoking urges, and
      more tobacco use. There were few gender differences. Despite a tendency to spend
      less time with peers, high-anxiety teenagers were more likely to show reduced
      anxiety when in the company of friends. Sharper differentiations among anxiety
      subgroups emerged when stratification was based on diary reports rather than on
      questionnaire scores. CONCLUSION: Even when anxiety problems fall below
      diagnostic thresholds, the daily lives of anxious adolescents differ meaningfully
      from those of their peers in affective, behavioral, and contextual domains.

PMID- 12049441
TI  - A DSM-IV-referenced, adolescent self-report rating scale.
AB  - OBJECTIVE: To examine the reliability and validity of the Youth's Inventory-4 (YI
      4), a DSM-IV-referenced self-report rating scale. METHOD: Youths (N = 239) aged
      between 11 and 18 years who were clinically evaluated between 1996 and 1999
      completed the YI-4, and 79% completed at least one additional self-report.
      Parents and teachers completed a companion measure. A second sample (N = 47) was
      retested 2 weeks after an initial evaluation. RESULTS: The YI-4 demonstrated
      satisfactory internal consistency (alpha values = .66-.87) and test-retest
      reliability (r values = 0.54-0.92), convergent and to lesser extent divergent
      validity with other self-report measures, and discriminant validity by
      differentiating children with and without diagnosed attention
      deficit/hyperactivity disorder, conduct disorder, substance use, generalized
      anxiety disorder, or major depressive disorder. Youth-parent (r values = 0.05
      0.50) and youth-teacher (r values < 0.18) agreement was generally modest.
      CONCLUSIONS: These findings provide preliminary support for the clinical utility
      of the YI-4 for symptom assessment in referred youths.

PMID- 12049442
TI  - Attention dysfunction predicts substance involvement in community youths.
AB  - OBJECTIVE: Cognitive impairments influence alcohol and drug treatment outcomes,
      though little is known about how neurocognition affects the development of
      harmful substance use patterns. This study examined the influence of adolescent
      attention functioning on the development of substance use problems in 66 high
      risk youths over an 8-year period. METHOD: Participants were community youths who
      were free from any history of substance use disorders, neurological illness, and
      mood, anxiety, or psychotic disorders at project intake and were administered
      neuropsychological tests and substance involvement interviews from ages 15
      through 23 on average. Substance involvement was assessed by self-report,
      resource person reports, and randomly sampled toxicology screens. RESULTS:
      Attention/executive functioning scores obtained at the intake neuropsychological
      assessment significantly predicted substance use and dependence symptoms 8 years
      later, even after controlling for intake substance involvement, gender,
      education, conduct disorder, family history of substance use disorders, and
      learning disabilities. CONCLUSIONS: These results suggest that adolescents with
      limited attentional abilities, but not necessarily attention
      deficit/hyperactivity disorder diagnoses, may be at risk for developing more
      problematic alcohol and drug involvement. Thus prevention and treatment efforts
      should target youths with attentional difficulties by using programs that are
      effective for those with compromised concentration and processing abilities.

PMID- 12049443
TI  - Evaluation of child therapy and caregiver training in the treatment of school
      refusal.
AB  - OBJECTIVE: To evaluate the relative efficacy of (1) child therapy, (2)
      parent/teacher training, and (3) the combination of child therapy and
      parent/teacher training in the treatment of anxiety-based school refusal. METHOD:
      Sixty-one school-refusing children (aged 7-14 years) from throughout Melbourne,
      Australia, were randomized to a child therapy program, a parent and teacher
      training program, or a combination of the two. Children were assessed before and
      after treatment, and at 4.5-month follow-up, by means of attendance records, self
      report of emotional distress and self-efficacy, parent and teacher reports of
      emotional distress, and clinician ratings of overall functioning. RESULTS:
      Statistically and clinically significant pretreatment-posttreatment change
      occurred for each group. Immediately posttreatment, child therapy appeared to be
      the least effective in increasing attendance. By follow-up, the attendance and
      adjustment of those in the child therapy group equalled that of children whose
      parents and teachers were involved in treatment, whether on their own
      (parent/teacher training) or together with their children (combined child therapy
      and parent/teacher training). CONCLUSION: Contrary to expectations, combined
      child therapy and parent/teacher training did not produce better outcomes at
      posttreatment or follow-up.

PMID- 12049444
TI  - Does maternal ADHD reduce the effectiveness of parent training for preschool
      children's ADHD?
AB  - OBJECTIVE: To assess the impact of maternal attention-deficit/hyperactivity
      disorder (ADHD) symptoms on the effectiveness of a parent training (PT) program
      for preschool ADHD. METHOD: Eighty-three 3-year-old children with ADHD and their
      mothers selected from two community cohorts living in Hampshire, England (1992-93
      and 1995-96, respectively), completed an 8-week PT program. ADHD symptoms and a
      number of other parent and child factors, including adult ADHD symptoms, were
      measured prior to the start of treatment (week 1: T1), immediately after
      treatment (week 8: T2), and at 15 weeks follow-up (week 23: T3). RESULTS: Mothers
      were divided into three groups on the basis of their scores (T1) on the Adult
      AD/HD Rating Scale (high, medium, low). Children of mothers in the high-ADHD
      group displayed no improvement after PT, whereas the levels of ADHD symptoms of
      the children of mothers in either the medium or low ADHD groups reduced
      substantially (F(4,60) = 3.13, p < .05). This association persisted after other
      child and maternal factors were controlled for in multiple regression analyses
      (beta > .30, p < .05). CONCLUSIONS: High levels of maternal ADHD symptoms limit
      the improvement shown by children with ADHD after a program of PT. This effect
      was unrelated to other aspects of maternal mental health and child functioning.
      The treatment of parental ADHD may be a prerequisite for the success of
      psychosocial interventions for childhood ADHD.

PMID- 12049445
TI  - ADHD and parental psychological distress: role of demographics, child behavioral
      characteristics, and parental cognitions.
AB  - OBJECTIVE: This study aimed to examine the relative roles of demographic, child
      behavioral, and parental characteristics in understanding the psychological
      distress suffered by parents of children with attention-deficit/hyperactivity
      disorder (ADHD). It was hypothesized that a combination of child and parent
      demographics, severity of child behavioral disturbance, low knowledge of ADHD,
      causal and controllability attributions internal to the child, along with lower
      perceived parental control, would be associated with more severe psychological
      distress, as measured by parenting stress and depression. METHOD: One hundred
      mothers were interviewed and provided ratings of behavioral disturbance, severity
      of ADHD, knowledge of ADHD, attributions of cause and controllability of ADHD
      related behaviors, parenting stress and depression. RESULTS: Hierarchical
      regression analyses indicated that the combination of these variables was
      significantly associated with parental psychological distress, accounting for 24%
      and 21% of the variance in parenting stress and depression, respectively. Unique
      contributions were evident for severity of behavioral disturbance and perceived
      parental control over child behaviors. Child's age, gender, medication status,
      and maternal education were controlled in the analyses. CONCLUSION: Results
      support the view that interventions for ADHD aimed only at child behavior are
      unlikely to alter long-term outcome.

PMID- 12049446
TI  - Bilingual children referred for psychiatric services: associations of language
      disorders, language skills, and psychopathology.
AB  - OBJECTIVE: To investigate (1) the prevalence of language deficits and disorders
      and (2) the relationship of bilingual language skills and psychopathology, in
      Spanish-English bilingual children referred for child and adolescent psychiatry
      services. METHOD: Bilingual language skills, emotional/behavioral problems,
      sociodemographics, immigration variables, and nonverbal IQ were studied in 50
      consecutively referred children. RESULTS: Estimated prevalence was high for
      language deficits (48%) and disorders (41%), with most cases (>79%) being of the
      mixed receptive-expressive type. In children with clinically significant
      emotional/behavioral problems, bilingual language skills were strongly and
      inversely correlated with problem scores, particularly global problems (r = 
      0.67, p < .001); social, thought, and attention problems (r > or = -0.54; p <
      .004); delinquency (r = -0.66, p < .001); and aggression (r = -0.52, p < .01).
      These correlations remained significant after IQ adjustment. CONCLUSIONS: Prior
      findings from monolingual children were confirmed in this bilingual sample,
      namely (1) the high prevalence of mixed receptive-expressive and other language
      disorders and delays and (2) the close tie between poor language skills and
      emotional/behavioral problems. The data strongly suggest the clinical importance
      and feasibility of language assessment and the significance of receptive problems
      in bilingual children referred for psychiatric services. A safe approach is to
      fully assess language skills, rather than misattributing these children's
      language delays to normal bilingual acquisition processes.

PMID- 12049447
TI  - Informant-specific correlates of suicidal behavior in a community survey of 12-
      to 14-year-olds.
AB  - OBJECTIVES: To arrive at a better estimation of informant-specific correlates of
      suicidal behavior in young adolescents and to see how agreements and
      discrepancies between child and parent informants can contribute to the
      development of research and interventions. METHOD: The weighted sample from the
      Quebec Child Mental Health Survey conducted in 1992 included 825 adolescents,
      aged 12 to 14 years, and their parents. The adolescent and one parent were
      questioned by two different interviewers. The response rate was 80.3%. Three
      categories of independent variables were assessed: adolescent, family, and
      socioeconomic characteristics. Logistic regression models were based on the
      adolescent and parent informant reports. RESULTS: Parents identified 6 of the 59
      adolescents having reported suicidal ideation and 2 of the 36 adolescents having
      reported suicide attempts. Two informant-specific models of correlates of
      suicidal behavior were found. The adolescent model included internalizing and
      externalizing mental disorders, family stressful events, and parent-adolescent
      relationship difficulties, while the parent model included perceiving a need for
      help for the adolescent, parent's depressive disorders, and parent-adolescent
      relationship difficulties. CONCLUSION: The study shows the relevance of
      considering informant-specific correlates of suicidal behavior in the development
      of research and interventions targeting youths suicidal behavior.

PMID- 12049448
TI  - Barriers to children's mental health services.
AB  - OBJECTIVE: To examine the characteristics associated with barriers to children's
      mental health services, focusing on the effect of children's psychosocial
      problems on parents. METHOD: Data come from a first-grade, prevention
      intervention project conducted in Baltimore, Maryland. Analyses were restricted
      to 116 families who participated in seventh-grade interviews and indicated the
      index child needed services. The Services Assessment for Children and Adolescents
      was used to measure barriers to children's mental health services. RESULTS: More
      than 35% of parents reported a barrier to mental health services. Types of
      barriers included those related to structural constraints, perceptions of mental
      health, and perceptions of services (20.7%, 23.3%, and 25.9%, respectively).
      Although parenting difficulties were associated with all barriers (structural: OR
      = 10.63, 95% CI: 2.37, 47.64; mental health: OR = 8.31, 95% CI: 1.99, 34.79;
      services: OR = 5.22, 95% CI: 1.56, 17.51), additional responsibilities related to
      attendance at meetings was associated only with structural barriers (OR = 5.49,
      95% CI: 1.22, 24.59). CONCLUSIONS: Researchers and policymakers interested in
      increasing children's access to mental health services should consider strategies
      to reduce barriers related to perceptions about mental health problems and
      services, in addition to structural barriers. Particular attention should be
      given to programs that focus on the needs of families who are most affected by
      their child's psychosocial problems.

PMID- 12049449
TI  - Cognitive-behavioral/interpersonal group treatment for anxious adolescents.

PMID- 12049450
TI  - Single-factor between-groups designs: analysis and interpretation.

PMID- 12049451
TI  - Genetics of childhood disorders: XXXIX. Stem cell research, part 3: Regulation of
      neurogenesis by stress and antidepressant treatment.

PMID- 12049452
TI  - Octomacrum europaeum (Monogenea: Octomacridae) in Europe: historical and recent
      perspectives.
AB  - Several specimens of Octomacrum europaeum (Octomacridae: Monogenea) were found on
      the gills of Alburnoides bipunctatus in the Czech Republic. The morphometry of
      the specimens measured in the present study was in agreement with that of the
      original description.

PMID- 12049453
TI  - Molecular cloning and characterization of Plasmodium falciparum transportin.
AB  - A cDNA encoding transportin, a protein involved in the nuclear import of M9
      nuclear localization signal-bearing proteins, has been cloned from the malaria
      parasite Plasmodium falciparum. The complete cDNA consists of 3,667 bp encoding
      1,136 amino acid residues. Amino acid sequence analysis revealed that Ran-GTP and
      M9 binding domains are highly conserved in P. falciparum, suggesting that the
      transportin-mediated nuclear transport pathway exists in this protozoan parasite.
      Southern blot analysis revealed that the transportin gene exists as a single copy
      in the malarial genome.

PMID- 12049454
TI  - Chemotherapeutic approaches to schistosomes: current knowledge and outlook.
AB  - The chemotherapy of schistosomiasis has improved greatly in the last few decades.
      There are three drugs available: metrifonate (active against Schistosoma
      haematobium), oxamniquine (active against Schistosoma mansoni) as narrow spectrum
      drugs and praziquantel, which is effective against all important adult
      schistosome species and their immature stages, as the drug of choice.

PMID- 12049455
TI  - Characterization of a recombinant mu-class glutathione S-transferase from Taenia
      solium.
AB  - A Taenia solium larval glutathione S-transferase fraction (SGSTF), composed of
      two proteins with Mr 25,500 (SGSTM1) and 26,500 (SGSTM2), was purified by GSH
      sepharose. Its N-terminal sequence analysis revealed that both proteins are
      related to mammalian mu-class GST enzymes. A cDNA clone coding for SGSTM1 was
      isolated and the amino acid sequence analysis showed close identity with two
      Echinococcus GSTs and also high identity with several mu-class GSTs that have
      been reported. In addition, SGSTM1 presents a similar structure to mu-class GSTs,
      including the mu loop. The recombinant SGSTM1 is a dimeric protein with enzymatic
      properties clearly related to mammalian mu-class GSTs. Western blot studies
      indicated that SGSTM1 is not antigenically related to SGSTM2 or mammalian GSTs
      from rabbit, pig and rat livers. Immunization with SGSTF and SGSTM2 was highly
      effective in reducing cysticerci load in murine cysticercosis. In contrast, no
      protection was obtained using native SGSTM1 and recombinant SGSTM1 as immunogens.

PMID- 12049456
TI  - Genotypically unique Babesia spp. isolated from reindeer (Rangifer tarandus
      tarandus) in the United States.
AB  - Two morphologically dissimilar Babesia spp. were cultured from reindeer (Rangifer
      tarandus tarandus) in Placer County, Calif. The smaller isolate, designated RD61,
      was morphologically similar to Babesia odocoilei. Serum from RD61-infected
      reindeer reacted equally strongly to B. odocoilei and RD61 parasites in the
      indirect fluorescent antibody (IFA) test. Small subunit ribosomal RNA (SSU rRNA)
      gene-sequence analysis showed 99.0% identity to that of B. odocoilei. The larger
      piroplasm, designated RD63, resembled larger babesia organisms, such as Babesia
      caballi and Babesia bigemina. Serum from RD63-infected reindeer also reacted with
      both B. odocoilei and RD61 parasites in the indirect fluorescent antibody test.
      The SSU rRNA gene showed 94.2% identity to that of B. bigemina. Further studies
      are needed to determine whether these parasites are the same as the Babesia spp.
      previously documented in Siberian reindeer.

PMID- 12049457
TI  - A common oocyst surface antigen of Cryptosporidium recognized by monoclonal
      antibodies.
AB  - Two hybridoma clones, CMYL3 and CMYL30, were generated by immunizing Balb/c mice
      with excysted oocysts of Cryptosporidium muris. Both clones secreted monoclonal
      antibodies against an oocyst-wall antigen with apparent molecular mass of 250 kDa
      (called CM250) from C. muris and C. parvum. The epitope appeared to be periodate
      sensitive, suggesting the involvement of a carbohydrate moiety.
      Immunofluorescence and confocal microscopy on purified oocysts and infected mouse
      tissues revealed staining confined to the oocyst wall of both Cryptosporidium
      species. Immunogold labeling further revealed the presence of the CM250 antigen
      in electron-dense vesicles and cytoplasm of developing macrogametocytes, and
      ultimately localized to the oocyst wall of mature oocysts. Both antibodies cross
      reacted with C. serpentis oocysts but did not recognize the other
      enteropathogenic protozoans Giardia muris, Eimeria falciformis and E. nischulz.
      These antibodies may be valuable tools for the analysis of oocyst-wall formation
      in Cryptosporidium and characterization of the common antigen.

PMID- 12049458
TI  - S-adenosylmethionine decarboxylase from Leishmania infantum promastigotes:
      molecular cloning and differential expression.
AB  - S-Adenosylmethionine decarboxylase (AdoMetDC), an enzyme involved in the
      synthesis of polyamines as well as in the cell methylation processes, has been
      considered in trypanosomes as a specific drug target. We have cloned by RT-PCR a
      DNA fragment of 1,364 bp which contains the open reading frame and the 5' end
      fragment of the AdoMetDC encoding gene from the parasite protozoon Leishmania
      infantum. The 1,197 bp ORF encodes for a 392 amino acid residue polypeptide. The
      sequence comparison with AdMetDC from different species showed a high level of
      homology, around 80%. with the American and African trypanosomes and a certain
      distance from the polypeptides of higher eukaryotes. AdoMetDC has been cloned in
      a pQE32 vector and overexpressed in a M15 Escherichia coli strain. The gene
      expression shows variations between the distinct phases of the parasite, being
      higher in the most infective one. This fact may be related to the multiple
      defense mechanism of the protozoon against the macrophage action.

PMID- 12049459
TI  - Oxidative and cold shock cause enhanced induction of a 50 kDa stress protein in
      Trichinella spiralis.
AB  - The anti-heat shock protein (Hsp)-90 monoclonal antibody AC-16 reacts on blots
      with Hsp90 and a 50 kDa protein (prot-50) from infective-stage (L1) larvae of the
      nematode Trichinella spiralis. We examined Hsp90 and prot-50 levels by
      densitometric analysis of immunoblots of T. spiralis larval extracts prepared
      before (time 0, 37 degrees C) and after oxidative [hydrogen peroxide (H2O2)]
      stress, or cold shock at 4 degrees C. Extracts from H2O2-exposed L1 were obtained
      after 2 h; the others at 2, 4, and 8 h after the temperature shift. After H2O2
      shock, the constitutive Hsp90 and prot-50 were both significantly induced and
      appeared as slower migrating inducible isoforms. However, whereas Hsp90 levels
      decreased after cold shock, prot-50 levels immediately and persistently increased
      after shock at 4 degrees C. These data present compelling evidence that the prot
      50 described here functions as a Hsp and a cold shock protein.

PMID- 12049461
TI  - A "pop off" technique for reprocessing histological sections of the paramyxean
      Marteilia sydneyi for electron microscopy.
AB  - A "pop off" technique is described for transferring paraffin-embedded tissue
      sections of Saccostrea glomerata infected with the paramyxean Marteilia svdneyi
      to resin blocks for electron microscopy. Paramyxean features that were clearly
      recognisable were cell-within-cell arrangements and organelles, such as
      haplosporosomes, vermiform vesicles and multivesicular bodies. These features are
      important for correct taxonomic identification.

PMID- 12049460
TI  - Larval Taenia crassiceps secretes a protein with characteristics of murine
      interferon-gamma.
AB  - Previous studies have shown that excretory/secretory products of larval Taenia
      crassiceps have immunomodulatory activities. We report here that one of these
      products, termed p66, possesses activities that mimic some characteristics of
      murine interferon-gamma (IFN-gamma). Purified p66 cross-reacts with anti-murine
      IFN-gamma on immunoblots and increases concanavalin-A-induced splenic T-cell
      proliferative responses of normal and chronically infected mice. It has also been
      shown that p66 induces enhanced IFN-gamma and interleukin-10 (IL-10) production
      in cells from infected or normal mice. Adherent and non-adherent peritoneal
      exudates cells were stimulated with p66 and showed that the adherent cells were
      induced to produce IL-10 and that the non-adherent cells were induced to produce
      IFN-gamma. p66 was shown as well to upregulate nitric oxide production in
      macrophages and two T-cell lines, IEL and YAC-1, were shown to be stimulated to
      produce IFN-gamma and IL-10, respectively, by p66. Although the significance of
      p66 in immunoregulation is not known, we show here that this molecule mimics
      characteristics of IFN-gamma.

PMID- 12049462
TI  - Development of a nested PCR assay to detect the pathogenic free-living amoeba
      Naegleria fowleri.
AB  - Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis,
      a fatal disease of the central nervous system that is acquired while swimming or
      diving in freshwater. A cDNA clone designated Mp2C15 obtained from N. fowleri was
      used as a probe to distinguish N. fowleri from other free-living amoebae. The
      Mp2C15 probe hybridized to genomic DNA from pathogenic N. fowleri and
      antigenically related non-pathogenic N. lovaniensis. Mp2C15 was digested with the
      restriction enzyme XbaI, resulting in two fragments, Mp2C15.G and Mp2C15.P. Four
      species of Naegleria and four species of Acanthamoeba were examined for
      reactivity with Mp2C15.P. Mp2C15.P was specific for N. fowleri and was used in
      the development of a nested PCR assay which is capable of detecting as little as
      5 pg of N. fowleri DNA or five intact N. fowleri amoebae. In summary, a rapid,
      sensitive, and specific assay for the detection of N. fowleri was developed.

PMID- 12049463
TI  - In vitro activity of polyoxin D and nikkomycin Z against Encephalitozoon
      cuniculi.
AB  - Microsporidia of the genus Encephalitozoon are emerging protozoal agents that
      mainly infect immunocompromised patients with AIDS. At present, disseminated
      infections with members of the genus Encephalitozoon can only be successfully
      treated with albendazole. As chitin is a basic component of the microsporidian
      spore. we evaluated, in vitro, the susceptibility of a human-derived strain of
      Encephalitozoon cuniculi to polyoxin D and nikkomycin Z, which are known
      competitive inhibitors of chitin synthetase enzymes. Using an in vitro assay,
      polyoxin D at 1, 10 and 100 microg/ml significantly reduced the number of
      parasitic foci on days 6, 9, and 15 post-infection. However, nikkomycin Z
      revealed a marked but lower reduction in the number of parasitic foci than
      polyoxin D. A significant reduction of parasitic foci was achieved for nikkomycin
      Z at 10 and 100 microg/ml up to day 9 post-infection. Polyoxin D was
      approximately tenfold more effective in our in vitro assay than nikkomycin Z.

PMID- 12049464
TI  - Effect of proteasome inhibitors on the growth, encystation, and excystation of
      Entamoeba histolytica and Entamoeba invadens.
AB  - The effect of three proteasome inhibitors, lactacystin, clasto-lactacystin beta
      lactone, and MG-132, on the growth, encystation, and excystation of Entamoeba
      histolytica and Entamoeba invadens was examined. All of these drugs blocked E.
      histolytica growth in a concentration-dependent manner; lactacystin was most
      potent for the inhibition and MG-132 showed the inhibitory effect only at higher
      concentrations. E. invadens was more resistant to these drugs than E.
      histolytica. Encystation of E. invadens was also inhibited and was more sensitive
      to the drugs than was growth. Beta-lactone was the most potent encystation
      inhibitor. The inhibitory effect of lactacystin and the beta-lactone on
      encystation was slightly and little abrogated by the removal of the drug,
      respectively. Multinucleation occurred in E. histolytica trophozoites treated
      with these drugs, being most marked with lactacystin. In contrast, no
      multinucleation was observed in E. invadens treated with the drugs. Electron
      microscopy revealed that the treatment of E. histolytica trophozoites with
      lactacystin led to an increase in the number of cells with many glycogen granules
      in the cytoplasm. Lactacystin, beta-lactone and MG-132 had no or little effect on
      the excystation and metacystic development of E. invadens. These results suggest
      that proteasome function plays an important role for Entamoeba growth and
      encystation, but has no obvious effect on excystation or metacystic development.

PMID- 12049465
TI  - Culture, isolation and propagation of Babesia caballi from naturally infected
      horses.
AB  - Thirteen blood samples of horses from South Africa, five of which were
      seropositive for Babesia caballi and eight for both B. caballi and Theileria
      equi, were subjected to in vitro culture to identify carrier animals. None of the
      animals had a detectable parasitaemia on Giemsa-stained blood smears before
      culture initiation. Cultures were initiated in L-cysteine-enriched medium, either
      in an oxygen-reduced gas mixture or in a 5% CO2-in-air atmosphere. All five
      animals seropositive for B. caballi were identified as carrier animals using an
      oxygen-reduced atmosphere, whereas only four samples became culture positive
      under normal atmospheric conditions. Among the eight samples seropositive for
      both B. caballi and T. equi, two were identified as carriers for both. The
      remaining six samples were identified as carrying only T. equi.

PMID- 12049466
TI  - Intestinal infusion of soluble larval antigen stimulates rejection of
      heterologous nematode larvae by immune sheep.
AB  - Sheep immunised by multiple truncated infections with Trichostronglyus
      colubriformis were highly resistant to subsequent challenge with homologous
      exsheathed larvae, administered via a surgically implanted duodenal cannula. The
      duration of immunity after truncated infections was 12-14 weeks against challenge
      with T. colubriformis or Cooperia curticei, but there was little cross-protection
      against challenge with Nematodirus spathiger. When immune sheep were given
      booster doses of T. colubriformis larvae before challenge with N. spathiger,
      there were 97% fewer N. spathiger larvae in the first 5 m of small intestine, and
      an overall 79% reduction of N. spathiger larvae in immunised sheep, compared with
      naive controls. Boosting T. colubriformis immune sheep with killed T.
      colubriformis larvae plus soluble T. colubriformis L3 antigen, or with soluble
      antigen alone, also caused significant displacement of N. spathiger challenge
      larvae (98% and 100% respectively), indicating a non-specific expulsion process.
      These results indicate that N. spathiger can be used as an indicator species in
      T. colubriformis immune sheep, to quantify the effects of stimulating mucosal
      immunity with specific antigens, which may lead to identification of the antigens
      required for immunisation against nematodes.

PMID- 12049467
TI  - Localization of post-translationally modified alpha-tubulin and pseudocyst
      formation in tritrichomonads.
AB  - The distribution of acetylated tubulin was investigated in members of the
      Tritrichomonadinae subfamily using a specific monoclonal antibody and indirect
      immunofluorescence microscopy. Species probed in this study were: Tritrichomonas
      foetus, T. mobilensis, T. muris, and an unnamed tritrichomonad isolated from the
      cecum of cotton rats (Sigmodon hispidus). Additionally, the distribution of
      glutamylated tubulin in T. muris was investigated using the GT 335 antibody to
      the glutamyl motif. Although acetylated alpha-tubulin was ubiquitously
      distributed throughout the axostyle and flagella of T. foetus and T. mobilensis,
      a distinct and unusual labeling pattern was observed in 'T. muris'-type or
      pseudocyst-forming trichomonads. In trophozoite stages of T. muris and the cotton
      rat isolate, flagella were intensely labeled, but acetylation of axostylar
      tubulin appeared to be limited to the anterior and posterior thirds. However,
      trophozoites labeled with an antibody to alpha-tubulin or glutamylated tubulin
      demonstrated no such discontinuity in axostylar staining. Additionally,
      pseudocysts labeled with anti-alpha-tubulin and anti-acetylated alpha-tubulin
      were all found to possess continuously fluorescent axostyles. That the mid-region
      axostyle remained unlabeled by anti-acetylated tubulin in trophozoites indicates
      possible deacetylase activity, which may have functional implications with
      respect to the life cycle. Glutamylated tubulin appeared to be distributed
      throughout the axostyle and flagella, which fluoresced brightly in T. muris.

PMID- 12049468
TI  - Polymorphisms in the parasite genes for pfcrt and pfmdr-1 as molecular markers
      for chloroquine resistance in Plasmodium falciparum in Lambarene, Gabon.

PMID- 12049469
TI  - Milestones of helmintic research at Bayer.

PMID- 12049470
TI  - Potential radiotherapy improvements with respiratory gating.
AB  - Gating is a relatively new and potentially useful therapeutic addition to
      external beam radiotherapy applied to regions affected by intra-fraction motion.
      The impact was of gating on treatment margins, image artifacts, and volume and
      positional accuracy was investigated by CT imaging of sinusoidally moving
      spheres. The motion of the spheres simulates target motion. During the CT imaging
      of dynamically moving spheres, gating reproduced the static volume to within 1%,
      whereas errors of over 20% were observed where gating was not used. Using a
      theoretical analysis of margins, gating alone or in combination with an
      electronic portal imaging device may allow a 2-11 mm reduction in the CTV to PTV
      margin, and thus less healthy tissue need be irradiated. Gating may allow a
      reduction of treatment margins, an improvement in image quality, and an
      improvement in positional and volumetric accuracy of the gross tumor volume.

PMID- 12049472
TI  - Compliance testing of medical diagnostic x-ray equipment: three years' experience
      at a major teaching hospital in Western Australia.
AB  - The impact of a formal compliance testing program has been evaluated three years
      post-implementation on a major teaching hospital (Sir Charles Gairdner Hospital)
      with 46 x-ray tubes located throughout 37 rooms. The mandatory program,
      implemented by the statutory authority in January 1997, called for all medical
      (including chiropractic and dental) equipment used in human diagnosis to be
      tested at prescribed frequencies using established protocols. The application of
      the required test methods demonstrated various non-compliance issues. Notices of
      non-compliance were received for approximately 60% of the equipment in the
      hospital following the equipment's first annual test. The reasons for, and the
      significance of, failure varied according to equipment category, test category,
      equipment use and equipment age. However, at the end of the third year of
      testing, approximately 75% of the tested x-ray units satisfied the compliance
      criteria. The main reasons for non-compliance were found to be design limitations
      of old technology and the current radiation legislation that makes it difficult
      for some older equipment to meet the relatively stringent criteria.

PMID- 12049471
TI  - Stereotactic synchrotron microbeam radiotherapy.
AB  - Highly collimated synchrotron x-ray beams with high fluence rate may be used in
      stereotactic radiotherapy of brain tumours. Several monochromatic x-ray beams
      having uniform microscopic thickness ie (microplanar beams) are directed to the
      center of the tumour from varying directions, delivering lethal dose to the
      target volume while sparing normal cells. This proposed technique takes advantage
      of the hypothesised repair mechanism of capillaries between closely spaced
      microplanar beam zones. The sharply dropping lateral dose profile of a
      microplanar beam provides low scattered dose to the off-target interbeam volume.
      In close proximity to the target volume, relatively high secondary electron doses
      close to the edge of the beams overlap and produce a high dose region between
      angled beams. This allows precise targeting and prevents gradual blurring of the
      higher and lower dose margins in the target volume. The advantages of
      stereotactic microplanar beam radiotherapy will be lost as the dose between
      microplanar beams exceeds the tolerance dose of the dose limiting tissues.
      Therefore to minimize the risks of delayed radiation damage it is essential to
      optimize the interbeam doses inside a human head phantom. The EGS4 Monte Carlo
      code is used to calculate the lateral dose profiles and depth dose of a 100 keV
      single microplanar beam in the phantom. A general equation for absorbed dose as a
      function of depth and lateral distances is derived for the single beam. Several
      microplanar beams are directed into the target volume at the center of the
      phantom. Using the equation, maximum dose on the beam axis (primary + total
      scattered dose) and the minimum interbeam dose (total scattered dose) are
      calculated at different depths and an isodose map of the phantom is obtained. A
      stereotactic microplanar beam radiotherapy model is proposed for a 10 mm diameter
      (approximately spherical) tumour at the center of the phantom.

PMID- 12049474
TI  - Microvascular permeability of rat cerebral pia mater by using image computer
      analysis.
AB  - Microcirculation viviperception and fluorescent tracer techniques were used and
      digital image analysis applied for quantitative measurement of fluorescein sodium
      (FiNa) permeability in microvessels of the cerebral pia mater. The diffusion
      permeation equations of FiNa within the blood vessels and through the vessel
      walls into the perivascular tissue of normal rats and ischemic rats were
      established with two vessels as study object, thus the permeation speed equations
      under different ischemic conditions were deduced. Based on analysis of the
      results, we deduced the relation between the permeability and the intersection
      angle of two vessels. RESULT: logarithm model showed a good fit of the experiment
      data. The permeation equation showed logarithmic distribution and then tended
      towards stability. FiNa could pass through microvessel walls with the highest
      speed in the one-hour ischemic rat group, and the permeation speed of FiNa in
      rats receiving reperfusion after twelve hours of ischemia was much faster than
      that in normal rats. CONCLUSION: the method can be useful for quantitative
      analysis of cerebral pia mater microvascular permeability

PMID- 12049473
TI  - In vitro studies of gadolinium-DTPA conjugated with monoclonal antibodies as
      cancer-specific magnetic resonance imaging contrast agents.
AB  - The monoclonal antibodies, 9.2.27 against human melanoma cell lines and WM53
      against leukemia cell lines, were conjugated with cyclic anhydride gadolinium
      diethylenetriaminepenta-acetic acid (Gd-cDTPAa) and used as tumor-specific
      contrast agents in magnetic resonance imaging (MRI). The data indicate that Gd
      DTPA-9.2.27 in solution decreased the T1 relaxation of water protons at 7.0 Tesla
      (300 MHz) in direct proportion to the gadolinium concentration, and this effect
      was greater than in Gd-DTPA solutions. These conjugates show high specificity for
      melanoma and leukemia cell lines. T1 relaxation time at 7.0 Tesla, measured for
      the melanoma cell line (MM-138) and leukemia cell line (HL-60) after incubation
      at 37 degrees C for 4 hr, were significantly decreased (approximately 25%)
      relative to controls. The gadolinium concentration in cells and washing solutions
      was measured by inductively coupled plasma atomic emission spectroscopy (ICP
      AES). A linear relationship was observed between T1 relaxation rates and
      gadolinium concentrations obtained by ICP-AES. The ICP-AES results showed no
      gadolinium uptake in the non-targeted HT-29 colorectal cancer cells.

PMID- 12049475
TI  - Optimisation of electron cone design in high energy radiotherapy using the Monte
      Carlo method.
AB  - Cylindrical solid-walled steel electron collimators are used at the Royal
      Adelaide Hospital with a Siemens KD2 Mevatron accelerator to produce circular
      fields 2-8 cm in diameter. The cones are used in contact with the patient's skin.
      A flat treatment field is required at the treatment depth and the beam should
      also satisfy the uniformity standards as specified by the International
      Electrotechnical Commission (IEC). However, the seven and eight centimetre
      diameter cones provided by the manufacturer did not meet these specifications. In
      particular, the maximum dose relative to the depth-dose maximum on the central
      axis exceeded 126% as compared with the IEC recommended value of 109%, when used
      with a 21 MeV electron beam. Cone modifications were previously investigated by
      others with the results demonstrating some improvement in the 'horn' (as it
      appears on surface dose profiles) but still not satisfying IEC requirements. In
      the present paper the EGS4 code was used to model the existing treatment head
      geometry and cones, as well as new suggested modifications to the cone. The
      results of the simulation for the existing cone geometry corresponded closely to
      previously obtained measurements. The suggested collimator modifications involved
      a plastic insert along the internal wall of the collimator. Variations of the
      insert width and height were simulated for a 21 MeV electron beam and the results
      plotted to indicate the optimal insert dimensions. A plastic insert with the
      dimensions taken from one of the best models was produced and tested. The
      measurements showed close agreement with the simulation results (for the 'horn'
      height, dose within 1% and radial position within 2 mm) and improvement of the
      "maximum ratio of absorbed dose" from 126% before modification to 108% with the
      plastic insert. The tested insert was also simulated for a 12 MeV electron beam,
      to see whether permanent fitting of such an insert would have a deleterious
      effect at lower energies. Neither penetration nor flatness was significantly
      compromised, with a small penalty being a slight increase in the central axis
      dose near the surface.

PMID- 12049476
TI  - Review: DNA molecular electrostatic potential: novel perspectives for the
      mechanism of action of anticancer drugs involving electron transfer and oxidative
      stress.
AB  - This report examines the mechanism of action of DNA-binding anticancer drugs that
      involve electron transfer and oxidative stress, and primarily focuses on
      neglected issues surrounding molecular electrostatic potentials (MEP), the
      energetics of initial guanine oxidation and the consequences of the sequence
      dependence of DNA structure on electron transport within a DNA duplex. We argue
      that an appreciation of electrostatic effects aids in shaping a more complete
      view of the electron transfer and DNA oxidation process. Some aspects concerning
      the MEP of DNA relevant to these events have lain dormant, whereas others
      represent novel insights. We discuss the impact of electrostatics on ligand
      binding to DNA, guanine oxidation, axial charge transport and hopping termination
      reactions. Another ignored feature for intercalating redox-active agents is the
      reversible nature of their interaction with DNA, which in principle permits
      catalytic regeneration of the unmodified ligand via redox cycling with generation
      of reactive oxygen species. Therefore, oxidative stress may be exerted on DNA at
      both ends of the charge transport chain. Hence, mechanistic treatments that
      neglect to take into account the importance of the MEP of DNA may be flawed or
      deficient in many cases. An increased understanding of the basic mechanisms of
      redox chemistry within DNA may aid in improved anticancer drug design.

PMID- 12049477
TI  - Antineoplastic agents 460. Synthesis of combretastatin A-2 prodrugs.
AB  - The original synthesis of combretastatin A-2 (1a) was modified to provide an
      efficient scale-up procedure for obtaining this antineoplastic stilbene.
      Subsequent conversion to a useful prodrug was accomplished by phosphorylation
      employing in situ formation of dibenzylchlorophosphite followed by cleavage of
      the benzyl ester protective groups with bromotrimethylsilane to afford the
      phosphoric acid intermediate 11. The latter was immediately treated with sodium
      methoxide to complete a practical route to the disodium phosphate prodrug (2a).
      The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel
      series of reactions to produce a selection of metal and ammonium cation prodrug
      candidates. Each of the phosphate salts (2a-q) was evaluated with respect to
      relative solubility behavior, cancer cell growth inhibition and antimicrobial
      activity.

PMID- 12049478
TI  - The desferrithiocin (DFT) class of iron chelators: potential as antineoplastic
      agents.
AB  - Iron (Fe) is essential for the proliferation of cancer cells. A subgroup of the
      orthosubstituted phenolate class of Fe chelators, desferrithiocin [2-(3'
      hydroxypyrid-2'-yl)4-methyl-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its
      analogues, have potential application in short-term chemotherapy for cancer by Fe
      deprivation. Their effects on cell proliferation, cell cycle progression, Fe
      uptake and toxicity were therefore examined in adult and fetal rat and human
      hepatocellular carcinoma (HCC) cell lines, as well as in normal cells. DFT was
      more active than desferrioxamine, in clinical trials as an antineoplastic agent,
      consistently inhibiting cell proliferation in all cell lines (IC50 = 40 microM).
      2-(2'-hydroxyphenyl-2'-yl)-delta2-thiazoline-4(S)-carboxylic acid was the most
      active analogue (IC50 = 55-90 microM). Inhibition was affected by chelator
      concentration and ability to prevent Fe uptake. The fetal-cell-derived HCC was
      more susceptible than adult HCC. Structure-activity studies revealed that thiazol
      methyl deletion greatly diminished antiproliferative activity of the chelators
      but stereochemical orientation of COOH around C4 had no effect. Removal of the N
      from the pyridine ring restored antiproliferative activity. Chelators inhibited
      DNA synthesis in the S phase. The chelators at their IC50 concentration had
      little or no effect on Fe uptake in normal cells. This apparent selectivity of
      these chelators for cancer cells, coupled with their high activity, suggests that
      further investigation is warranted.

PMID- 12049479
TI  - Inhibition of superoxide dismutase by 2-methoxyoestradiol analogues and oestrogen
      derivatives: structure-activity relationships.
AB  - Superoxide dismutases catalyse the dismutation of highly reactive superoxide ions
      to produce hydrogen peroxide and several lines of evidence suggest that these
      enzymes play important roles in the development and response to treatment of
      human cancers. For example, Mn-containing superoxide dismutase is frequently
      overexpressed in various cancer types and can contribute to resistance to
      apoptosis. 2-Methoxyoestradiol is a naturally occurring metabolic product of
      17beta-oestradiol that inhibits tubulin polymerization and possesses growth
      inhibitory and cytotoxic activity in vitro and in vivo. More recently 2
      methoxyoestradiol has also been shown to inhibit superoxide dismutase (SOD) in a
      tetrazolium salt based enzyme assay, suggesting that oestrogen derivatives might
      be useful starting points for the development of effective, non-toxic enzyme
      inhibitors. Here we have tested the SOD inhibiting activity of a range of
      oestrogen derivatives to determine structural features important for enzyme
      inhibition.

PMID- 12049480
TI  - 1-[(Benzofuran-2-yl)phenylmethyl]triazoles as steroidogenic inhibitors: synthesis
      and in vitro inhibition of human placental CYP19 aromatase.
AB  - Hormone-dependent breast cancer is stimulated by the female hormones oestrone and
      oestradiol, therefore compounds which inhibit the specific enzymes involved in
      the formation of the nitogenic hormones, namely CYP19 aromatase (P450arom) and
      17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 1, are targets of
      therapeutic interest for the treatment of breast cancer. A series of novel 1
      [(benzofuran-2-yl)phenylmethyl]1,2,4-triazoles were prepared using a three-step
      synthesis and evaluated for their inhibitory activity against human placental
      aromatase in vitro, using [1,2,6,7-3H]androstenedione as the substrate for the
      aromatase enzyme. Inhibitory activity was dependent on both substituent and
      position of substitution, with introduction of small electron-withdrawing groups
      in the phenyl ring showing optimum activity (IC50 ranging from 0.065 to 2.02
      microm). Substitution in the benzofuran ring resulted in a loss of activity when
      substituted at C-5 (IC50 > 20 microm). The compounds were all shown to exhibit
      weak inhibitory activity against rat testes P450 17 (17,20-lyase), indicating
      good selectivity towards P450arom.

PMID- 12049482
TI  - The inhibition of acetylcholinesterase by irinotecan and related camptothecins:
      key structural properties and experimental variables.
AB  - Irinotecan (CPT-11), a water-soluble and semi-synthetic topoisomerase I poison of
      the camptothecin family, has activity against both adult and paediatric
      malignancies. Recently, we demonstrated that CPT-11 (lactone) is also a potent
      inhibitor of human acetylcholinesterase (AChE) at clinically relevant
      concentrations. Attachment of heterocyclic and branched amino groups onto the
      camptothecin back-bone continues to be a strategy for the synthesis of water
      soluble analogues, but this may lead to undesirable inhibition of AChE. In this
      study, we screened a range of camptothecin analogues, degradation products and
      metabolites for their ability to inhibit AChE. Those compounds possessing N
      substitutions at C-10 were all found to inhibit AChE in a similar kinetic manner
      to CPT-11, but with a broad range of potencies. It is recognized that the charge
      state is important for ligands that bind to the peripheral anionic site and we
      postulated that the protonated distal piperidine of CPT-11 would be important. To
      address this question, an N-methyl piperidinium iodide analogue was synthesized
      and tested. This derivative inhibited electric eel AChE with an inhibition
      constant (Ki) of 1 nM. Kinetic and deacylation experiments demonstrated that it
      acted relatively less as an inhibitor of deacylation than CPT-11. Overall, our
      experiments reveal that nitrogenous substitutions at the permissive C-10 of the
      camptothecin backbone may lead to AchE inhibition, particularly if they involve a
      quaternary nitrogen.

PMID- 12049481
TI  - Mode of action of methotrexate-albumin in a human T-cell leukemia line and
      activity against an MTX-resistant clone.
AB  - Limitations of low mol. wt anticancer drugs are short tumor exposure times and
      toxicity to normal tissue. Methotrexate (MTX) covalently linked to human serum
      albumin (HSA) as a macromolecular carrier caused tumor regressions concomitant
      with a favorable toxicity profile in a clinical phase I trial (Hartung et aL,
      Clin. Cancer Res., 1999, 5, 753). We examined the uptake, intracellular
      degradation, metabolism and thymidylate synthase (TS) inhibition of MTX-HSA in
      the T-cell leukemia line CCRF-CEM and the MTX transport resistant clone CCRF
      CEM/MTX. The number of MTX molecules per albumin molecule was determined by
      electrospray mass spectrometry. A loading ratio (LR) of approximately 1.4 mol
      MTX/albumin revealed intact complexes with one and two MTX molecules/albumin. In
      the complex with an LR of 5.7, albumin with up to 16 MTX molecules was seen. MTX
      HSA was taken up by CCRF-CEM cells via endocytosis and cleaved by lysosomal
      enzymes. Liberated MTX was a poor substrate of folylpolyglutamate synthetase and
      was exported into the medium. TS was inhibited and cell survival was impaired by
      MTX-HSA in a time- and concentration-dependent manner. CCRF-CEM/MTX cells
      exhibited a growth inhibition of 30-40% after MTX-HSA treatment, but no TS
      inhibition. The alternative uptake route via endocytosis enables MTX-HSA to
      overcome transport resistance to MTX.

PMID- 12049483
TI  - Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.
AB  - A new method for synthesis of four spin-labeled structural analogues of the
      antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl
      nitrite for nitrosation of the intermediate spin-labeled ureas has been
      described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6
      tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of
      bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We
      measured the tissue distribution of 3b in organ homogenates of C57BL mice by an
      electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly
      localized in the lungs. Our results strongly support the development and
      validation of a new approach for synthesis of less toxic nitrosourea derivatives
      as potential synergists of antitumor drugs.

PMID- 12049484
TI  - Reversal of P-glycoprotein associated multidrug resistance by new isoprenoid
      derivatives.
AB  - To find a drug to overcome P-glycoprotein associated multidrug resistance, we
      synthesized 43 new isoprenoid derivatives. Ten compounds were effective in an in
      vitro assay with the human MDR-type resistant carcinoma KB/VJ-300 and MRP-type
      KB/VP-4 cell lines. One of the most effective compounds, N-5228 [trans-N,N'
      bis(3,4-dimethoxybenzyl)-N-solanesyl-1,2-diaminocyclohexane, mol. wt 1100.481,
      was tested in P388/VCR-bearing mice. It showed a antitumor effect on MDR-type
      resistant tumor cells. Moreover, N-5228 potentiated the accumulation of
      [3H]vincristine in drug-resistant cells and blocked [3H]azidopine photoaffinity
      labeling of P-glycoprotein molecules in MDR-type resistant cell membranes. We
      think that N-5228 is promising as a lead compound in the screening of resistance
      reversing drugs for multidrug resistant cancers.

PMID- 12049485
TI  - Evaluation of USP apparatus 3 for dissolution testing of immediate-release
      products.
AB  - We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as
      an alternative to USP apparatus 2 for dissolution testing of immediate-release
      (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly
      soluble drugs, acyclovir and furosemide, were chosen as model drugs. The
      dissolution profiles of both innovator and generic IR products were determined
      using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute
      (dpm). The dissolution profiles from USP apparatus 3 were compared to those from
      USP apparatus 2 using the f(2) similarity test. The dissolution profile from USP
      apparatus 3 generally depends on the agitation rate, with a faster agitation rate
      producing a faster dissolution rate. It was found that USP apparatus 3 at the
      extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic
      conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation
      rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2
      or distinguish dissolution characteristics for the IR products of metoprolol,
      ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide
      tablets using USP apparatus 3. Although it is primarily designed for the release
      testing of extended-release products, USP apparatus 3 may be used for the
      dissolution testing of IR products of highly soluble drugs, such as metoprolol
      and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir.
      USP apparatus 3 offers the advantages of avoiding cone formation and mimicking
      the changes in physiochemical conditions and mechanical forces experienced by
      products in the gastrointestinal tract.

PMID- 12049486
TI  - Ocular tolerance of absorption enhancers in ophthalmic preparations.
AB  - The use of absorption promoters is a way to improve the bioavailability and
      therapeutic response of topically applied ophthalmic drugs. The ocular tolerance
      of 9 potential absorption promoters was investigated as well as the influence of
      the enhancers' concentration on the ocular tolerance. The substances tested were
      instillated repetitively (4 times per day, during 3 days, and once just before
      examination) as aqueous solutions onto rabbit corneas. Fluorescein dyeing enabled
      us to specifically mark corneal damage that was observed by confocal microscopy.
      The degree of corneal injury was assessed with an image-processing system that
      calculated the total fluorescent areas. Confocal microscopy results showed the
      relatively good tolerance of permeation enhancers like dimethyl sulfoxide (DMSO),
      decamethonium, edetate, glycocholate, and cholate in contrast to the poorly
      tolerated saponin and fusidate. Increasing the promoters' concentration led
      generally to an increase in corneal lesions.

PMID- 12049487
TI  - Application of confocal laser scanning microscopy in characterization of chemical
      enhancers in drug-in-adhesive transdermal patches.
AB  - The purpose of this study was to evaluate the application of confocal laser
      scanning microscopy (CLSM) in the examination of the embedment and the release
      characteristics of chemical permeation enhancers from transdermal drug delivery
      systems (TDDSs) of the "drug-in-adhesive" type. The enhancer lauric acid and a
      lauric acid fluorescing probe of the Bodipy type were incorporated into TDDSs
      consisting of an acrylic, a polyisobutylene, or a silicone polymer adhesive.
      Three-dimensional confocal images of the distribution were obtained before and
      during release into an aqueous medium. The images showed that the lauric acid
      fluorescing probe was homogeneously embedded in all the adhesives except for 1
      polyisobutylene. The release profiles and release rate constants of the lauric
      acid fluorescing probe were consistent with data from a release study of lauric
      acid performed using conventional measurements of the released amounts. This
      indicated that lauric acid was distributed in a homogeneous manner. Furthermore,
      it was possible to illustrate the mechanics of the diffusion process inside the
      TDDS and compare these patterns with theoretically drawn profiles, based on
      Fick's law of diffusion. CLSM was demonstrated to be an excellent tool to study
      how enhancers are incorporated and diffuse into a TDDS.

PMID- 12049489
TI  - Selected physical and chemical properties of commercial Hypericum perforatum
      extracts relevant for formulated product quality and performance.
AB  - OBJECTIVE: The complex composition-activity relationship of botanicals such as St
      John's Wort (SJW) presents a major challenge to product development, manufacture,
      and establishment of appropriate quality and performance standards for the
      formulated products. As part of a larger study aimed at addressing that
      challenge, the goals of the present study are to (1) determine and compare the
      phytochemical profiles of 3 commercial SJW extracts; (2) assess the possible
      impact of humidity, temperature, and light on their stability; and (3) evaluate
      several physical properties important to the development of solid dosage forms
      for these extracts. METHODS: An adapted analytical method was developed and
      validated to determine phytochemical profiles and assess their stability. The
      extract physical properties measured were particle size (Malvern Mastersizer),
      flow (Carr's compressibility index; minimum orifice diameter), hygroscopicity
      (method of Callahan et al), and low-pressure compression physics (method of Heda
      et al). RESULTS: The phytochemical properties differed greatly among the extracts
      and were extremely sensitive to changes in storage conditions, with marked
      instability under conditions of elevated humidity. All extracts exhibited
      moderate to free-flow properties and were very hygroscopic. Compression
      properties varied among the extracts and differed from a common use excipient,
      microcrystalline cellulose. CONCLUSIONS: Three commercial sources of SJW extracts
      exhibited different physical and chemical properties. Standardization to 1 or 2
      marker compounds does not ensure chemical equivalence nor necessarily equivalent
      pharmacological activity. Flow and compression properties appear suitable for
      automatic capsule-filling machines, but hygroscopicity and the moisture
      sensitivity of the phytochemical profile are concerns.

PMID- 12049488
TI  - Protein binding predictions in infants.
AB  - Plasma binding protein levels are lower in the newborn than in the adult and
      gradually increase with age. At birth, human serum albumin (HSA) concentrations
      are close to adult levels (75%-80%), while alpha 1-acid glycoprotein (AAG) is
      initially half the adult concentration. As a result, the extent of drug binding
      to HSA is closer to that of the adult than are those drugs bound largely to AAG.
      A model that incorporates the fraction unbound in adults and the ratio of the
      binding protein concentration between infants and adults successfully predicted
      the fraction unbound in infants and children.

PMID- 12049490
TI  - Skeletal effects of parathyroid hormone (1-34) in ovariectomized rats with or
      without concurrent administration of salmon calcitonin.
AB  - This study evaluated the effect of parathyroid hormone (PTH) infusion alone or in
      combination with salmon calcitonin (sCT) in ovariectomized (OVX) rats and
      compared it with daily PTH injections alone or in combination with sCT infusion.
      Female Sprague-Dawley rats were divided randomly into 6 groups and were either
      bilaterally ovariectomized or underwent a sham operation; they were then treated
      for 4 weeks, beginning the day after surgery. Each group of OVX rats received
      either PTH infusion (group 1), PTH + sCT infusion (group 2), sCT infusion + daily
      PTH injection (group 3), or daily PTH injection (group 4). One group each of OVX
      (group 5) and sham-operated rats (group 6) received daily injections of vehicle
      alone. PTH was injected at 80 microg/kg/day and infused at 40 microg/kg/day,
      whereas sCT was infused at 10 microg/kg/day. The animals were sacrificed 28 days
      after treatment, and cancellous bone volume was measured in the tibial
      metaphysis. Similar to daily PTH injections, continuous infusion of PTH alone
      increased cancellous bone volume significantly over that seen in vehicle-treated
      OVX and sham-operated rats. Although cancellous bone volume after continuous
      infusion of PTH + sCT was also significantly higher than that seen in vehicle
      treated OVX and sham-operated rats, the increase was significantly lower than
      with the other 3 nonvehicle treatments. The increase in cancellous bone volume
      after administration of sCT infusion along with daily PTH injections was not
      different from that with daily PTH injections alone. Thus, at the doses tested,
      the beneficial effects of PTH injection were not apparently improved by PTH
      infusion or by combination with sCT.

PMID- 12049491
TI  - Electronic and resonance effects on the ionization of structural analogues of
      efavirenz.
AB  - The solubility of 4 analogues of efavirenz was studied as a function of pH. The
      study evaluated the ionization behavior and determined the relative contribution
      of electronegative substituents versus resonance effects on the pK(a) value of
      the cyclic carbamate. The most profound lowering effect on the pK(a) was due to
      the presence of multiple electronegative substituents and in particular the
      trifluoromethyl and acetylene groups. The presence of chlorine on the
      benzoxazinone ring was found to have a slight impact on the pK(a), although to a
      lesser extent. In the absence of any functional groups on the benzoxazinone ring
      system, the pKa shifted to a value of 13.2, which is 3 pH units above that of
      efavirenz and more closely correlates with typical literature values for cyclic
      carbamates.

PMID- 12049494
TI  - Single nucleotide polymorphisms of the human M1 muscarinic acetylcholine receptor
      gene.
AB  - The gene encoding the human muscarinic receptor, type 1 (CHRM1), was genotyped
      from 245 samples of the Coriell Collection (Coriell Institute for Medical
      Research, Camden, NJ). Fifteen single nucleotide polymorphisms (SNPs) were
      discovered, 9 of which are located in the coding region of the receptor. Of
      these, 8 represent synonymous SNPs, indicating that CHRM1 is highly conserved in
      humans. Only a single allele was found to contain a nonsynonymous SNP, which
      encodes an amino acid change of Cys to Arg at position 417. This may have
      functional consequences because a C417S point mutation in rat M1 was previously
      shown to affect receptor binding and coupling. Furthermore, 0 of 4 SNPs within
      CHRM1 previously deduced from sequencing of the human genome were found in this
      study despite a prediction that a majority of such inferred SNPs are accurate.
      The consensus sequence of CHRM1 obtained in our study differs from the deposited
      reference sequence (AC NM_000738) in 2 adjacent nucleotides, leading to a V173M
      change, suggesting a sequencing error in the reference sequence. The
      extraordinary sequence conservation of the CHRM1 gene-coding region was
      unexpected as M1-knockout mice show only minimal functional impairments.

PMID- 12049492
TI  - Allometric scaling of xenobiotic clearance: uncertainty versus universality.
AB  - Statistical analysis and Monte Carlo simulation were used to characterize
      uncertainty in the allometric exponent (b) of xenobiotic clearance (CL). CL
      values for 115 xenobiotics were from published studies in which at least 3
      species were used for the purpose of interspecies comparison of pharmacokinetics.
      The b value for each xenobiotic was calculated along with its confidence interval
      (CI). For 24 xenobiotics (21%), there was no correlation between log CL and log
      body weight. For the other 91 cases, the mean +/- standard deviation of the b
      values was 0.74 +/- 0.16; range: 0.29 to 1.2. Most (81%) of these individual b
      values did not differ from either 0.67 or 0.75 at P = 0.05. When CL values for
      the subset of 91 substances were normalized to a common body weight coefficient
      (a), the b value for the 460 adjusted CL values was 0.74; the 99% CI was 0.71 to
      0.76, which excluded 0.67. Monte Carlo simulation indicated that the wide range
      of observed b values could have resulted from random variability in CL values
      determined in a limited number of species, even though the underlying b value was
      0.75. From the normalized CL values, four xenobiotic subgroups were examined:
      those that were (i) protein, and those that were (ii) eliminated mainly by renal
      excretion, (iii) by metabolism, or (iv) by renal excretion and metabolism
      combined. All subgroups except (ii) showed a b value not different from 0.75. The
      b value for the renal excretion subgroup (21 xenobiotics, 105 CL values) was
      0.65, which differed from 0.75 but not from 0.67.

PMID- 12049493
TI  - Receptor binding studies of soft anticholinergic agents.
AB  - Receptor binding studies were performed on 24 soft anticholinergic agents and 5
      conventional anticholinergic agents using 4 cloned human muscarinic receptor
      subtypes. The measured pK(i) values of the soft anticholinergic agents ranged
      from 6.5 to 9.5, with the majority being in the range of 7.5 to 8.5. Strong
      correlation was observed between the pK(i) s determined here and the pA 2 values
      measured earlier in guinea pig ileum contraction assays. The corresponding
      correlation coefficients (r2) were 0.80, 0.73, 0.81, and 0.78 for pK(i) (m1),
      pK(i) (m2), pK(i) (m3), and pK(i) (m4), respectively. Quantitative structure
      activity relationship (QSAR) studies were also performed, and good
      characterization could be obtained for the soft anticholinergics containing at
      least 1 tropine moiety in their structure. For these compounds, the potency as
      measured by the pK i values was found to be related to geometric, electronic, and
      lipophilicity descriptors. A linear regression equation using ovality (O(e)),
      dipole moment (D), and a calculated log octanol-water partition coefficient
      (QLogP) gave reasonably good descriptions (r = 0.88) for the pK(i) (m3) values.

PMID- 12049495
TI  - The cytoplasmic escape and nuclear accumulation of endocytosed and microinjected
      HPMA copolymers and a basic kinetic study in Hep G2 cells.
AB  - The development of macromolecules as drugs and drug carriers requires knowledge
      of their fate in cells. To this end, we studied the internalization and
      subcellular Fate of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers in Hep G2
      (human hepatocellular carcinoma) cells. Semiquantitative fluorometry confirmed
      that galactose was an effective ligand for receptor-mediated endocytosis for Hep
      G2 cells. The rate of internalization of a galactose-targeted copolymer was
      almost 2 orders of magnitude larger than that of the nontargeted copolymer.
      Confocal fluorescent microscopy of both fixed and live cells revealed that the
      polymer entered the cells by endocytosis. After longer incubation times
      (typically >8 hours), polymer escaped from small vesicles and distributed
      throughout the cytoplasm and nuclei of the cells. Polymer that entered the
      cytoplasm tended to accumulate in the nucleus. Microinjection of the HPMA
      copolymers into cells' cytoplasm and nuclei indicated that the polymers
      partitioned to the nucleus. The data from fixed cells was confirmed by microscopy
      of live, viable cells. To examine the effect of the fluorescent dye on the
      intracellular fate, polymers with fluorescein, Oregon Green 488, Lissamine
      rhodamine B, and doxorubicin were tested; no significant differences were
      observed.

PMID- 12049496
TI  - A national survey of U.S. pharmacists in 2000: assessing nonresponse bias of a
      survey methodology.
AB  - The first objective of this study was to assess the existence of nonresponse bias
      to a national survey of licensed pharmacists conducted in 2000. Three methods
      were used to assess nonresponse bias. The second objective of the study was to
      examine reasons why sampled licensed pharmacists did not respond to the national
      survey of licensed pharmacists. We used data from 2204 respondents to a national
      survey of pharmacists and from 521 respondents to a survey of nonrespondents to
      the national survey. We made comparisons between respondents for 5 variables:
      employment status, gender, age, highest academic degree, and year of initial
      licensure. Chi-square tests were used to examine differences in the 5 variables
      between respondents to the first mailing and second mailing of the survey, early
      and late respondents to the survey, and respondents to the survey and respondents
      to the nonrespondent survey. There were no significant differences between first
      mailing and second mailing respondents, but there were differences in each
      variable except year of licensure between early and late respondents. These
      differences likely were due to regional bias possibly related to differences in
      mailing times. There were differences between respondents and nonrespondents in
      terms of employment status and year of licensure. The main reasons for not
      responding to the survey were that it was too long or that it was too intrusive.
      Overall, the survey methodology resulted in a valid sample of licensed
      pharmacists. Nonresponse bias should be assessed by surveying nonrespondents.
      Future surveys of pharmacists should consider the length of the survey and the
      address where it is sent.

PMID- 12049497
TI  - Stereocontrolled [3 + 2] annulations with arene chromium tricarbonyl complexes:
      construction of spirocyclic compounds related to fredericamycin A.
AB  - [reaction: see text] An efficient method has been developed for the
      stereocontrolled construction of polycyclic and spirocyclic compounds, including
      the spirocyclic core of the antitumor agent fredericamycin A. The strategy
      involves a one-pot aldol addition/Brook rearrangement/cyclization sequence
      beginning from arene chromium tricarbonyl complexes and can formally be described
      as a [3 + 2] annulation.

PMID- 12049498
TI  - Redox-based spin diversity in a 6-oxophenalenoxyl system: generation,
      ESR/ENDOR/TRIPLE, and theoretical studies of 2,5,8-tri-tert-butylphenalenyl- 1,6
      bis(olate) salts.
AB  - [reaction: see text] Novel open-shell molecular salts, 2,5,8-tri-tert
      butylphenalenyl-1,6-bis(olate) salts, were designed on the basis of the 6
      oxophenalenoxyl system and generated by the chemical reduction of 6
      hydroxyphenalenone derivatives. ESR/ENDOR/TRIPLE measurements and DFT
      calculations provide unequivocal determination of the structure and spin density
      distribution, which demonstrate redox-based spin diversity of the 6
      oxophenalenoxyl system.

PMID- 12049499
TI  - Catalytic asymmetric cyclopropanation using bridged dirhodium tetraprolinates on
      solid support.
AB  - Dirhodium tetraprolinates in highly cross-linked macroporous polystyrene resins
      are very effective catalysts for asymmetric cyclopropanation using methyl
      aryldiazoaceates.

PMID- 12049500
TI  - Highly active thermomorphic fluorous palladacycle catalyst precursors for the
      Heck reaction; evidence for a palladium nanoparticle pathway.
AB  - [reaction: see text] The fluorous Schiff base p
      Rf8(CH2)3C6H4C(=N(CH2)3Rf8)(CH2)2Rf8 (Rf8 = n-C8F17) is prepared in six steps
      from p-iodobenzaldehyde and then cyclopalladated (Pd(OAc)2) to give highly
      effective catalyst precursors for Heck reactions, conducted under homogeneous
      conditions (DMF, 80-140 degrees C, turnover numbers >10(6)) in the absence of
      fluorous solvents. Rate, recycling, and other data suggest that the palladacycles
      serve as sources of palladium nanoparticles, which are the dominant active
      catalysts.

PMID- 12049501
TI  - Silver-promoted reactions of bicyclo[3.2.1]octadiene derivatives.
AB  - [reaction: see text] Highly substituted bicyclo[3.2.1]octadiene building blocks
      are easily prepared from tetrachloro- or tetrabromocyclopropene through reaction
      with cyclic dienes. These polyhalogenated derivatives can serve as precursors to
      a variety of functionalized bridged bicyclic compounds. Herein, we report on the
      generation and reaction of electrophilic species with silver ion.

PMID- 12049502
TI  - Diastereoselective conjugate additions to pi-allylmolybdenum complexes: a
      stereocontrolled route to 3,4,5-trisubstituted gamma-butyrolactones.
AB  - [reaction: see text] pi-Allylmolybdenum complex 6b is obtained as a single isomer
      by Knoevenagel condensation of aldehyde 1 with Meldrum's acid. Conjugate
      additions of Grignard reagents to Meldrum's acid alkylidene derivative 6b are
      shown to be completely diastereoselective. Further functional group
      transformation of the 1,4-adducts, followed by demetalation, leads to
      trisubstituted tetrahydrofurans and gamma-butyrolactones. Whereas the synthesis
      of tetrahydrofurans (X = 2H) is not completely stereoselective, the gamma
      butyrolactones (X = O) are obtained with good to excellent
      diastereoselectivities.

PMID- 12049503
TI  - Chemo-, regio-, and enantioselective Pd-catalyzed allylic alkylation of
      indolocarbazole pro-aglycons.
AB  - [reaction: see text] Monosubstituted isomerically pure indolopyrrolocarbazole
      precursors have been prepared via palladium-catalyzed asymmetric allylic
      alkylation methodology, employing both achiral cyclopentenyl electrophiles and
      chiral glycal derivatives. Chemoselective allylation of (bis)indole lactam pro
      aglycon 3 allows access to N-distally substituted indolopyrrolocarbazole
      derivatives; glyoxamide precursor 14 provides entry into N-proximally substituted
      derivatives.

PMID- 12049504
TI  - Synthesis of prodrug candidates: conjugates of amino acid with nucleoside
      boranophosphate.
AB  - [structure: see text] Preparation of antiviral and anticancer prodrug candidates,
      P-tyrosinyl(P-O)-5'-P-nucleosidyl boranophosphates, is described. One-pot
      synthesis via a phosphoramidite method resulted in the title compounds with good
      yields. The P-boranophosphate diastereomers were separated by RP-HPLC, and their
      structures were confirmed by 1H and 31P NMR spectroscopy and MS analysis.

PMID- 12049505
TI  - Photobleaching of compounds of the 5,10,15,20-Tetrakis(m-hydroxyphenyl)porphyrin
      Series (m-THPP, m-THPC, and m-THPBC).
AB  - [reaction: see text] 5,10,15,20-Tetrakis(m-hydroxyphenyl)porphyrin (m-THPP)
      yielded novel quinonoid porphyrins upon irradiation in aqueous methanol. True
      photobleaching was observed for 5,10,15,20-tetrakis(m-hydroxyphenyl)chlorin (m
      THPC) and 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (m-THPBC) under the
      same conditions; several fragmentation products (imides, methyl p
      hydroxybenzoate, dipyrrin derivatives) were recognized.

PMID- 12049506
TI  - A novel and highly stereoselective approach to aza-spirocycles. A short total
      synthesis of 2-epi-(+/-)-perhydrohistrionicotoxin and an unprecedented
      decarboxylation of 2-pyrones.
AB  - [reaction: see text] A novel and highly stereoselective synthesis of aza
      spirocycles is described. An application of this methodology is illustrated as a
      short and concise total synthesis of 2-epi-(+/-)-perhydrohistrionicotoxin with
      high diastereomeric control at the aza-spirocenter. An unprecedented
      decarboxylation of the 2-pyrone ring is observed in this total synthesis effort.

PMID- 12049507
TI  - A new and efficient chemoenzymatic route to both enantiomers of 4-hydroxycyclohex
      2-en-1-one.
AB  - [reaction: see text] A chemoenzymatic synthesis of both enantiomers of the
      pharmacologically interesting 4-hydroxycyclohex-2-en-1-one in three steps
      starting from 3-methoxycyclohex-2-en-1-one is described. Manganese(III) acetate
      mediated acetoxylation followed by enzyme-mediated hydrolysis of alpha-acetoxy
      enone affords acetoxy enone 3 and hydroxy enone 4 with high enantiomeric excesses
      and in good yields. The reduction of the acetoxy and hydroxy enones furnished
      both enantiomers of 4-hydroxycyclohex-2-en-1-one in high enantiomeric excess.

PMID- 12049508
TI  - Indium trichloride mediated intramolecular Prins-type cyclization.
AB  - [reaction: see text] Intramolecular Prins-type reactions of compounds having both
      functionalities of homoallyl alcohol and acetal moiety are described. The
      intramolecular Prins cyclizations were performed using indium trichloride in
      chloroform or 25% aqueous THF. Both 9-oxabicyclo[3.3.1]nonane and 3,9
      dioxabicyclo[3.3.1]nonane compounds were successfully obtained in moderate
      yields.

PMID- 12049509
TI  - Stereoselective synthesis of 2,5,6-trisubstituted piperidines.
AB  - [reaction: see text] A short and efficient synthesis of 2,5,6-trisubstituted
      piperidines was achieved by a combination of an aza-Achmatowicz oxidation of a
      furyl benzenesulfonamide, conjugate addition to the resulting 2H-pyridinone, and
      subsequent addition of various nucleophiles to a transient N-sulfonyliminium ion.
      The steric bulk of the tosyl group directs attack of the nucleophile from its
      opposite side, thereby leading to the formation of cis-substituted products.

PMID- 12049510
TI  - Phosphonate aldehyde annulation. A one-pot synthesis of delta-hydroxy
      cyclopentenoic esters.
AB  - [reaction: see text] The reaction of ketone enolates with phosphonate aldehyde 2
      afforded cyclopentenols 3 or keto esters 4 in a one-pot procedure.

PMID- 12049511
TI  - Stereoselective radical reactions of some tartaric and glyceric acid derivatives.
AB  - [reaction: see text] Free radicals generated by the decarboxylation of
      dimethoxydioxanecarboxylic acids derived from L-(+)-tartaric acid and L-glyceric
      acid added to some maleimides and acrylates with high stereoselectivity. This
      method provides easy access to some chiral building blocks.

PMID- 12049512
TI  - Solution-phase hexasaccharide synthesis using glucosyl iodides.
AB  - [reaction: see text] Oligosaccharides composed of 1,6-glucosyl residues have been
      prepared from glucosyl iodides. The reactions are highly stereoselective, giving
      the alpha-glycosides as the only isolated products in yields ranging from 84% to
      94%. Oligomer synthesis can take place in an iterative 1 + 1 + 1 fashion or in a
      convergent manner where dimer iodides serve as donors for higher order acceptors.

PMID- 12049513
TI  - Stereocontrolled total synthesis of (-)-ebelactone A.
AB  - [structure: see text] The highly stereocontrolled hydroboration of an alkene, a
      subsequent Suzuki-Miyaura cross-coupling reaction, a silylcupration on a
      nonterminal acetylene, and an iododesilylation were the key steps in a convergent
      total synthesis of (-)-ebelactone A.

PMID- 12049514
TI  - Synthesis and biological activity of hydroxamic acid-derived vasopeptidase
      inhibitor analogues.
AB  - [structure: see text] Syntheses of novel hydroxamic acid-derived azepinones
      containing pendant mercaptoacyl groups or formyl hydroxamates are described.
      These new analogues of therapeutically important ACE and NEP inhibitors include
      unprecedented changes at the previously assumed essential acid component.

PMID- 12049516
TI  - Synthesis of primary amines: first homogeneously catalyzed reductive amination
      with ammonia.
AB  - [reaction: see text] The synthesis of primary amines via reductive amination of
      the corresponding carbonyl compounds with aqueous ammonia is achieved for the
      first time with soluble transition metal complexes. Up to an 86% yield and a 97%
      selectivity for benzylamines were obtained in the case of various benzaldehydes
      by using a Rh-catalyst together with water-soluble phosphine and ammonium
      acetate. In the case of aliphatic aldehydes, a bimetallic catalyst based on Rh/Ir
      gave improved results.

PMID- 12049515
TI  - Synthesis of cyclosporin A-derived affinity reagents by olefin metathesis.
AB  - [reaction: see text] New affinity reagents were synthesized using alkene
      metathesis to directly modify the MeBmt side chain of cyclosporin A. The reagents
      were used to detect novel cyclophilins from cellular extracts.

PMID- 12049517
TI  - Highly stereoselective protonation of the enolate of a bicyclic cycloheptatrienyl
      lactone occurs on the hindered face.
AB  - [reaction: see text] The H/D exchange of the lactone-fused cycloheptatriene 1 is
      over 1000 times faster than that of the epimer 2. Interconversion of 1 and 2
      provides an equilibrium mixture of 1:0.7, showing a similar stability of the
      isomers. Protonation of the common enolate 7 occurs far more readily on the more
      hindered face. Cycloheptatrienide anion is bent and as stable as a
      divinylcarbanion.

PMID- 12049518
TI  - A convergent synthesis of the tricyclic architecture of the guanacastepenes
      featuring a selective ring fragmentation.
AB  - [reaction: see text] This Letter describes a concise, diastereoselective
      synthesis of the tricyclic carbon framework of the guanacastepene family of
      natural products. An intermolecular Diels-Alder reaction established a remote
      stereochemical relationship and facilitated a synthesis of allylic acetate 3,
      which was subsequently joined with vinylstananne 9 via a Stille coupling. An
      intramolecular [2 + 2] photocycloaddition then afforded complex cyclobutyl ketone
      19, which underwent a stereoelectronically controlled fragmentation to the
      guanacastepene architecture on treatment with samarium diiodide.

PMID- 12049519
TI  - A first synthesis of thiophene dendrimers.
AB  - [structure: see text] Thiophene dendrons and dendrimers were designed and
      synthesized using a convergent approach. Metal-mediated coupling reactions were
      used in the synthesis. A rational approach allowed the formation of alphaalpha,
      betabeta, and alphabeta linkages between the dendrons and thiophene units.

PMID- 12049520
TI  - An expedient synthesis of highly functionalized naphthyridones and quinolines
      from a common N-aryl pyridinone template.
AB  - [reaction: see text] We describe herein a new base-mediated process for the
      formation of N-arylpyridinones 2 and their use for the preparation of
      naphthyridones and quinolines. The cyclization of various hindered enamines with
      methyl propiolate proceeds efficiently in the presence of NaOH to afford the
      corresponding N-arylpyridinones. These substrates were then found to undergo
      subsequent cyclizations to afford highly functionalized naphthyridones and
      quinolines.

PMID- 12049521
TI  - Cobalt-mediated synthesis of angular [4]phenylene: structural characterization of
      a metallacyclopentadiene(alkyne) intermediate and its thermal and photochemical
      conversion.
AB  - [reaction: see text] The first X-ray crystal structure of a mononuclear
      metallacyclopentadiene(alkyne) complex has been obtained. This type of
      metallacycle is believed to be the key intermediate in the cobalt-mediated [2 + 2
      + 2]cycloaddition of alkynes. Thermal treatment leads to the generation of
      angular [4]phenylene, the X-ray structural details of which are described. Under
      photochemical conditions, the cobaltacycle isomerizes to a highly strained
      (cyclobutadieno)dibenzocyclooctatrienyne complex.

PMID- 12049523
TI  - New polyfluorinated organotin reagents. Stereoselective synthesis of (Z)-alpha
      fluoro-beta-trifluoromethylvinylstannanes.
AB  - [reaction: see text] A new methodology for the synthesis of (Z)-alpha-fluoro-beta
      trifluoromethylvinylstannanes, which are useful polyfluorinated organotin
      reagents for the synthesis of fluorine-containing biologically active compounds,
      is described.

PMID- 12049522
TI  - Palladium-imidazolium carbene catalyzed Mizoroki-Heck coupling with aryl
      diazonium ions.
AB  - [reaction: see text] Catalyst formed from N,N-bis(2,6
      diisopropylphenyl)dihydroimidazolium chloride and palladium(II) acetate (2 mol %)
      was used, without added base, to efficiently produce Heck coupled products with
      olefins and aryl diazonium tetrafluoroborate substrates. The reactions were
      performed at room temperature, giving product in 2-4 h with 80-90% yields for
      isolated materials. Diazonium ions, formed in situ directly from anilines, also
      couple under these conditions.

PMID- 12049524
TI  - Amphotericin B dimers with bisamide linkage bearing powerful membrane
      permeabilizing activity.
AB  - [structure: see text] Covalently linked dimers of amphotericin B were prepared by
      cross-linking its carboxylic acid. Among these, a dimer with a linkage of 1,6
      hexanediamine revealed potent hemolytic activity (EC50, 0.25 microM) while its N
      acetyl derivative gave rise to large K+ ion flux in phosphatidylcholine
      liposomes, regardless of the presence or absence of sterols, suggesting that the
      dimers may serve as a tool for elucidating the structure of the ion channel
      assemblage formed by amphotericin B.

PMID- 12049525
TI  - A modified approach to 2-(N-aryl)-1,3-oxazoles: application to the synthesis of
      the IMPDH inhibitor BMS-337197 and analogues.
AB  - [structure: see text] A modified approach to the synthesis of 2-(N-aryl)-1,3
      oxazoles, employing an optimized iminophosphorane/heterocumulene-mediated
      methodology, and its application to the synthesis of BMS-337197, a potent
      inhibitor of IMPDH, are described.

PMID- 12049526
TI  - A novel cyclodepsipeptide, HA23, from a Fusarium sp.
AB  - [reaction: see text] HA 23, a novel cyclodepsipeptide (1) of mixed peptide
      polyketide origins, was isolated from a fungal isolate of a Fusarium sp. The
      structure was determined from 1D and 2D NMR and mass spectral data.

PMID- 12049527
TI  - Unique ionic iodine atom transfer cyclization: a new route to iodomethylated
      pyrrolidine derivatives from gamma-iodoolefin and chloramine-T.
AB  - [reaction: see text] Pyrrolidines and bicyclic pyrrolidine derivatives can
      effectively be synthesized from gamma-iodoolefins using commercially available
      chloramine-T (CT) as a nitrogen source. The cyclization proceeds with high
      stereoselectivity via a cyclic iodonium intermediate.

PMID- 12049528
TI  - A theoretical investigation into the inversion barrier of dipole-stabilized alpha
      aminoorganolithiums.
AB  - [reaction: see text] Results from density functional theory calculations (B3LYP/6
      31+G) suggest that inversion of the monomer of 2-lithio-N-formylpyrrolidine (2)
      in coordinating ethereal solvent occurs with an activation barrier of 15.7
      kcal/mol, while the inversion of the monomer in a noncoordinating hydrocarbon
      solvent is considerably slower. However, aggregation into a trimer in hydrocarbon
      solvent restores the low inversion barrier. This study suggests that solvation
      and aggregation may influence the mechanism and rate of racemization of dipole
      stabilized alpha-aminoorganolithiums.

PMID- 12049529
TI  - Diastereoselective formation of indanes from arylboronate esters catalyzed by
      rhodium(I) in aqueous media.
AB  - [reaction: see text] Arylboronate esters bearing a pendant Michael-acceptor
      alkene can add to norbornene and cyclize to give indane systems in yields ranging
      from 62% to 95% with high diastereomeric excess (>20:1). The reaction is
      performed in an organic/aqueous emulsion and catalyzed using [Rh(COD)Cl]2 with t
      Bu-amphos chloride, a sterically bulky, electron-rich, water-soluble phosphine
      ligand.

PMID- 12049530
TI  - A practical enantioselective total synthesis of the bengamides B, E, and Z.
AB  - [reaction: see text] A practical total synthesis of Bengamides B, E, and Z from a
      common polyol intermediate is described. Consecutive aldol condensations afford a
      protected polyol thioester side chain suitable for coupling to the Bengamides. A
      novel chiral phase transfer catalyzed enantioselective alkylation affords the
      more highly functionalized amino caprolactams required for Bengamides B and Z.
      Use of the 2-naphthylmethyl ether protecting group, compatible with the boron
      Lewis acids required for enantioselective aldol condensation, allows direct
      access to Bengamide B.

PMID- 12049531
TI  - New hybrid inorganic-organic polymers as supports for heterogeneous catalysis: a
      novel Pd(0) metalated cyclophosphazene-containing polymer as an efficient
      heterogeneous catalyst for the Heck reaction.
AB  - [reaction: see text] A new Pd(0) complex of a pendant cyclophosphazene-containing
      cross-linked polymer is found to be an effective heterogeneous catalyst for the
      Heck arylation reaction. The catalyst is robust and can be recycled without
      significant loss of activity.

PMID- 12049532
TI  - Scientific data from clinical trials: investigators' responsibilities and rights.

PMID- 12049533
TI  - Genotype-phenotype analysis in multiple endocrine neoplasia type 1.
AB  - HYPOTHESIS: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is an autosomal
      dominant disorder caused by germline mutations in the MEN1 gene and characterized
      by multiple endocrine tumors, most notably in the parathyroid glands, pituitary,
      and pancreas. The syndrome demonstrates variable expressivity and considerable
      genetic heterogeneity. Patient data were examined for possible associations
      between genotype and phenotype. DESIGN: We reviewed recorded medical data from
      1975 to 2001 on patients with MEN 1 and compared specific types and locations of
      MEN1 gene mutations with manifestations of the syndrome. PATIENTS AND RESULTS: We
      identified 109 affected patients from 24 MEN 1 kindreds. The phenotypic
      expression of MEN 1 in affected individuals included hyperparathyroidism in 74%,
      pancreatic endocrine tumors in 51%, and pituitary tumors in 35%. Twelve of 14
      insulinomas occurred in patients with pituitary tumors. Mutation analysis was
      completed in 14 of 24 kindreds (80 of the 109 patients). Mutations were most
      common in exons 2 (31%), 9 (15%), and 10 (23%). All 21 patients with frameshift
      mutations (and known pancreatic endocrine tumor status) had such tumors.
      Pituitary tumors were associated with frameshift mutations in exon 2.
      CONCLUSIONS: The type and location of MEN1 mutations may be associated with the
      phenotypic expression of specific tumors. Such information may assist in the
      genetic counseling and surveillance of at-risk patients. A specific genotype
      phenotype correlation is unlikely because of the heterogeneity of the mutations
      in the MEN1 gene.

PMID- 12049534
TI  - A prospective, randomized trial of laparoscopic polytetrafluoroethylene (PTFE)
      patch repair vs simple cruroplasty for large hiatal hernia.
AB  - HYPOTHESIS: Large hiatal hernias are prone to disruption, resulting in
      reherniation, when repaired with simple cruroplasty. The use of mesh may decrease
      the rate of reherniation in the laparoscopic repair of large hiatal hernias.
      DESIGN: Prospective, randomized controlled trial. SETTING: University-affiliated
      private hospital. PATIENTS: Seventy-two individuals undergoing laparoscopic
      Nissen fundoplication with a hernia defect greater or equal to 8 cm in diameter.
      INTERVENTION: Nissen fundoplication with posterior cruroplasty (n = 36) vs Nissen
      fundoplication with posterior cruroplasty and onlay of polytetrafluoroethylene
      (PTFE) mesh (n = 36). MAIN OUTCOME MEASURES: Recurrences, complications, hospital
      stay, operative time, and cost. RESULTS: Patients in both groups had similar
      hospital stays, but the PTFE group had a longer operative time. The cost of the
      repair was $960 +/- $70 more in the group with the prosthesis. Complications were
      minor and similar in both groups. There were 8 hernia recurrences (22%) in the
      primary repair group and none in the PTFE group (P<.006). CONCLUSION: The use of
      prosthetic reinforcement of cruroplasty in large hiatal hernias may prevent
      hernia recurrences.

PMID- 12049535
TI  - Comparison of transarterial chemoembolization in patients with unresectable,
      diffuse vs focal hepatocellular carcinoma.
AB  - HYPOTHESIS: Transarterial chemoembolization (TACE) is beneficial for selected
      patients with unresectable hepatocellular carcinoma (HCC). DESIGN AND SETTING: A
      prospective comparison study in a tertiary hospital. STUDY PERIOD: November 21,
      1995, to May 2, 2001, with a mean follow-up of 939 days. PATIENTS: A total of 157
      TACE treatments were performed in 88 patients with unresectable HCC: 132
      treatments in 69 patients with focal HCC (F-HCC) and 25 treatments in 19 patients
      with diffuse HCC (D-HCC). INTERVENTIONS: Transarterial chemoembolization
      consisted of selective catheterization and intra-arterial infusion of a mixture
      of doxorubicin hydrochloride, cisplatin, and mitomycin followed by embolization.
      Sequential treatments were performed for bilobar HCC. MAIN OUTCOME MEASURES:
      Child-Pugh classification and clinical outcomes, including alpha-fetoprotein
      (AFP) response, length of hospital stay, readmission rate, and survival, were
      compared between patients with F-HCC and D-HCC following TACE using the chi(2)
      test, Fisher exact test, or t test (2-tailed, unpaired). RESULTS: Fifty-eight
      patients (84%) in the F-HCC group and 18 patients (95%) in the D-HCC group had
      cirrhosis. For those patients with cirrhosis, 58 (100%) in the F-HCC group and 14
      (78%) in the D-HCC group had a Child-Pugh score of A or B (P =.002). The mean
      baseline AFP was higher in the D-HCC group: 55 577 vs 7815 ng/mL in the F-HCC
      group (P =.001). Of the patients secreting AFP, 4 (29%) of 14 in the D-HCC group
      and 30 (68%) of 44 in the F-HCC group had a significant decrease in AFP 1 month
      following TACE (P =.01). The mean hospital stay was longer (3 vs 1.9 days; P
      =.001), and readmissions occurred more frequently (44% vs 9%; P<.001) in the D
      HCC group. The mean survival rate was significantly higher in the F-HCC group:
      425 vs 103 days (P<.001). CONCLUSIONS: In patients with F-HCC, TACE is well
      tolerated and provides a survival benefit. However, there is no apparent benefit
      for patients with D-HCC. Importantly, tumor characteristics and hepatic reserve
      are essential criteria for successful TACE.

PMID- 12049536
TI  - Pitfalls of intraoperative quick parathyroid hormone monitoring and gamma probe
      localization in surgery for primary hyperparathyroidism.
AB  - HYPOTHESIS: Intraoperative quick parathyroid hormone (qPTH) monitoring and gamma
      probe (GP) localization greatly aid the surgeon. DESIGN: Prospective case series
      of patients undergoing parathyroidectomy (PTX) with preoperative localization
      studies, operative data (including intraoperative qPTH values and GP
      localization), and outcomes. Follow-up was complete (mean, 4.2 months). SETTING:
      University teaching hospital. PATIENTS: We studied 57 consecutive patients with
      primary hyperparathyroidism from December 1, 1999, through November 30, 2000. Of
      these, 51 underwent first-time PTX, and 6, reoperative PTX (rePTX). MAIN OUTCOME
      MEASURES: Cure rate and morbidity after PTX or rePTX; sensitivity and accuracy of
      preoperative localization studies; prediction of cure from results of qPTH
      monitoring (comparing Nichols [>50% fall from the highest baseline level and
      lower than the lowest baseline] or normal-limit [>50% fall from first baseline
      level and lower than upper limit of the reference range] criteria); and value of
      GP localization. RESULTS: Patients were cured in 50 (98%) of 51 PTX and 6 (100%)
      of 6 rePTX for single adenomas (n = 49), double adenomas (n = 4), and multigland
      hyperplasia (n = 3). Nichols criteria for qPTH monitoring correctly categorized
      45 (92%) of 49 cured single adenomas 10 minutes after excision. Only 35 (71%) of
      these adenomas were correctly categorized as cured by means of the normal-limit
      criteria. In double adenomas, both sets of criteria in the 10-minute samples
      indicated unresected glands in only 2 of 4 cases. Preoperative sestamibi
      parathyroid scans correctly localized 38 (76%) of 50 single adenomas. The GP was
      used in 54 of 57 cases. All adenomas measured greater than 20% of background ex
      vivo, but 6 thyroid nodules also measured greater than 20% ex vivo. In double
      adenomas, the GP helped locate the second adenoma in only 1 of 4 cases. The GP
      was graded as crucial in 2 cases with dense scar (both rePTX), helpful in 12
      (22%) of 54 cases (particularly in retroesophageal glands), confirmatory in 32
      (59%), and not helpful in 8 (15%). The GP helped localize 3 (43%) of 7 glands not
      seen on sestamibi parathyroid scans. CONCLUSIONS: Intraoperative qPTH monitoring
      confirmed cure in most cases. For single adenomas, use of the Nichols criteria
      for qPTH assessment allowed more accurate and faster confirmation than the normal
      limit criteria. The GP was less useful but was crucial in 2 rePTX cases; it was
      not specific for parathyroid tissue. Both techniques have potential pitfalls that
      could result in surgical failure.

PMID- 12049537
TI  - Celiac arterial aneurysms: a critical reappraisal of a rare entity.
AB  - HYPOTHESIS: We hypothesize that although rare true aneurysms of the celiac artery
      carry a definite risk for rupture, current indications for elective intervention
      remain elusive and management has varied. To assess indications, the risks of
      surgical repair, and the morbidity of rupture, we reviewed our experience.
      DESIGN: We undertook a retrospective medical chart review of all patients with
      true celiac arterial aneurysms from our institutions from January 1, 1980,
      through December 31, 1998. We excluded patients with thoracoabdominal aneurysms
      and pseudoaneurysms. We followed up patients via medical records and/or telephone
      calls to the patient or a relative. RESULTS: Of 306 patients with visceral
      arterial aneurysms, true celiac arterial aneurysms were identified in 18 (5.9%),
      including 12 men (67%) and 6 women (33%) with a mean age of 64.2 years. Twelve
      patients (67%) had concomitant associated aneurysms at the time of presentation
      (8 aortic, 2 renal, 1 popliteal, and 1 femoral). Aneurysm size ranged from 1.5 to
      4.0 cm. Only 1 patient (6%) in our series presented with a ruptured aneurysm. Of
      the 17 patients with intact aneurysms, 9 (53%) underwent intervention, including
      revascularization in 8 (4 prosthetic, 2 saphenous vein, and 2 primary
      arterioarterial anastomoses). There was no operative mortality. In follow-up,
      both saphenous vein grafts were found to be occluded at 1 and 6 months after
      operation. Among the 9 patients treated nonoperatively, 1 late rupture resulted
      in death. Eight patients (44%) were alive without symptoms after a mean follow-up
      of 91 months (range, 1-371 months). CONCLUSIONS: Celiac arterial aneurysms are
      rare, but rupture occurs, and elective repair should be considered in good-risk
      patients with aneurysms of greater than 2 cm. An association with nonvisceral
      arterial aneurysms is frequent. Long-term results with prosthetic grafts have
      been excellent and should be the conduit of choice for noninfected aneurysms.

PMID- 12049538
TI  - Extended hepatectomy in patients with hepatobiliary malignancies with and without
      preoperative portal vein embolization.
AB  - HYPOTHESIS: Preoperative portal vein embolization (PVE) allows potentially
      curative hepatic resection without additional morbidity or mortality in patients
      with hepatobiliary malignancies who are marginal candidates for resection based
      on small liver remnant size. DESIGN: A retrospective review of a consecutive
      series of patients in a multi-institutional database who underwent extended
      hepatectomy. SETTING: University-based referral centers. PATIENTS: Forty-two
      patients underwent preoperative determination of the future liver remnant (FLR)
      volume before extended hepatectomy (> or = 5 segments) for hepatobiliary
      malignancy without chronic underlying liver disease. Patients were stratified by
      treatment with or without preoperative PVE. INTERVENTION: Preoperative
      percutaneous PVE. MAIN OUTCOME MEASURES: Clinical characteristics, FLR volume,
      operative morbidity, and survival. RESULTS: There was no difference between the
      groups that did and did not undergo PVE for the number of tumors, tumor size,
      estimated blood loss, duration of the operation, complexity of resection, or
      surgical margins. The FLR at presentation was significantly smaller in patients
      who underwent PVE than in patients who did not undergo PVE (18% vs 23%; P<.001).
      After PVE, FLR volumes increased significantly (P =.003); preoperative FLR
      volumes were similar in both groups (patients who underwent PVE, 25%; and
      patients who did not undergo PVE, 23%). There was no perioperative mortality and
      no statistical difference in the incidence of perioperative complications between
      those who did and those who did not undergo PVE (5 [28%] of 18 patients vs 5
      [21%] of 24 patients). The overall 3-year survival was 65% and the median
      survival duration was equivalent in the 2 groups (40 vs 52 months for those who
      did vs those who did not undergo PVE). CONCLUSION: Portal vein embolization
      enables safe and potentially curative extended hepatectomy in a subset of
      patients who would otherwise be marginal candidates for resection based on a
      small liver remnant size.

PMID- 12049539
TI  - Pheochromocytomas and paragangliomas in von Hippel-Lindau disease: a role for
      laparoscopic and cortical-sparing surgery.
AB  - HYPOTHESIS: Von Hippel-Lindau disease (VHL) is an autosomal-dominant disorder
      characterized by benign and malignant tumors involving the central nervous
      system, kidneys, pancreas, adrenal glands, and paraganglia. Appropriate
      management of pheochromocytomas and paragangliomas in VHL is evolving as we
      better understand the genetics and natural course of the disease and master
      advanced surgical techniques for adrenalectomy. DESIGN: Retrospective chart
      review. SETTING: Tertiary referral center. PATIENTS: A total of 109 patients
      identified at the Mayo Clinic, Rochester, Minn, with VHL (60 males and 49
      females) between January 1, 1975, and June 30, 2000. Seventeen patients (16%) had
      an identifiable adrenal mass and 3 patients had paragangliomas. Follow-up was
      complete in all but 2 patients. MAIN OUTCOME MEASURES: Clinical presentation,
      preoperative evaluation, surgical management, and outcome. RESULTS: Three
      patients with paragangliomas and 13 of 17 patients with adrenal masses underwent
      surgical resection. Median age at time of diagnosis was 30 years (range, 16-47
      years); 8 (40%) were asymptomatic. Fractionated urinary catecholamine and
      metanephrine concentrations were normal in one third of patients. Computed
      tomographic scanning identified 20 (83%) of 24 tumors. Adrenalectomies were
      performed as unilateral or bilateral, open or laparoscopic, and, finally, total
      or cortical-sparing. Seven (50%) of the patients underwent other concurrent
      abdominal procedures. There were no deaths, with an overall operative morbidity
      of 2 patients (14%). Only the 2 patients in whom bilateral total adrenalectomies
      were performed became corticosteroid dependent. No recurrences have been noted to
      date. CONCLUSIONS: A multidisciplinary approach is imperative for proper
      examination and monitoring of patients with VHL. Evaluation should begin early in
      life and always before elective surgery and childbirth. All adrenal masses in
      patients with VHL should be thoroughly evaluated and most should be resected.
      Early intervention and advanced surgical techniques better allow for cortical
      sparing and laparoscopic procedures. With low recurrence rates, corticosteroid
      independence can be maintained for prolonged periods.

PMID- 12049540
TI  - Similar functional results and complications after ileal pouch-anal anastomosis
      in patients with indeterminate vs ulcerative colitis.
AB  - HYPOTHESIS: Patients who undergo ileal pouch-anal anastomosis (IPAA) for
      indeterminate colitis (IC) have a pouch complication and pouch loss rate only
      slightly higher than that associated with ulcerative colitis (UC). The functional
      outcome in patients with IC is no different from that in patients with UC.
      DESIGN: Retrospective review of prospectively gathered data comparing
      complication rates and outcomes of patients with IC vs UC who have undergone IPAA
      at a single institution during 19 years. SETTING: University teaching hospital.
      PATIENTS: Between July 1, 1982, and July 1, 2001, 723 patients underwent IPAA,
      644 for colonic inflammatory bowel disease. A further breakdown of the latter
      group revealed 79 patients (12.3%) with IC and 565 (87.7%) with UC. These 2
      patient populations were compared with regard to postoperative complications,
      pouch loss, and functional outcome. MAIN OUTCOME MEASURES: Patients with IC and
      UC were compared with regard to pouch complications, such as J-pouch leak,
      fistula, cuff abscess, stricture, redo IPAA, Crohn diagnosis, and pouch loss.
      They were also compared with regard to 24-hour stool frequency and nighttime
      incontinence at 1, 3, 6, and 9 months after surgery. RESULTS: Approximately 98%
      of patients had 1 year of follow-up and 89% had long-term follow-up (mean, 78.5
      months). Patients with IC were compared with those with UC with regard to pouch
      complications, such as cuff abscess (1.3% vs 1.6%), J-pouch leak (5.1% vs 2.3%),
      intra-abdominal abscess (0% vs 1.1%), stricture (7.6% vs 4.8%), and fistula (2.5%
      vs 1.6%). These 2 groups were also compared with regard to small bowel
      obstruction (6.3% vs 5.5%), pouchitis (34.2% vs 25.0%), eventual diagnosis of
      Crohn disease (1.3% vs 0.7%), redo IPAA (1.3% vs 0.9%), and eventual pouch loss
      (2.5% vs 1.2%). An evaluation of functional results revealed no significant
      differences between the 2 groups with regard to 24-hour stool frequency or
      nighttime incontinence. The pathologists classified patients with IC into 3
      groups: IC but favor UC (group 1), IC but favor Crohn (group 2), and IC (group
      3). Most of the postoperative complications occurred in group 1 patients, but the
      only pouch loss occurred in those in group 2. CONCLUSIONS: The incidences of
      pouch complications after IPAA were slightly higher in the IC group compared with
      the UC group, but the differences were not statistically significant. Functional
      results were the same in both groups. Pouch loss was high in group 2 patients,
      but was otherwise not significantly higher in the IC group overall (P =.36). Most
      patients with IC can undergo IPAA and expect an outcome equivalent to that of
      patients with UC.

PMID- 12049541
TI  - Prospective evaluation of the safety of enoxaparin prophylaxis for venous
      thromboembolism in patients with intracranial hemorrhagic injuries.
AB  - BACKGROUND: Patients with traumatic intracranial hemorrhagic injuries (IHIs) are
      at high risk for venous thromboembolism (VTE). The safety of early
      anticoagulation for IHI has not been established. HYPOTHESIS: Enoxaparin can be
      safely administered to most patients with IHI for VTE prophylaxis. SETTING: Level
      I trauma center. DESIGN: Prospective, single-cohort, observational study.
      PATIENTS AND METHODS: One hundred fifty (85%) of 177 patients with blunt IHI
      received enoxaparin beginning approximately 24 hours after hospital admission
      until discharge. Brain computed tomographic (CT) scans were performed at
      admission, 24 hours after admission, and at variable intervals thereafter based
      on clinical course. Patients were excluded for coagulopathy, heparin allergy,
      expected brain death or discharge within 48 hours, and age younger than 14 years.
      Complications of enoxaparin prophylaxis were defined as Marshall CT grade
      progression of IHI, expansion of an existing IHI, or development of a new
      hemorrhagic lesion on follow-up CT after beginning enoxaparin use. RESULTS:
      Thirty-four patients (23%) had CT progression of IHI. Twenty-eight CT scans (19%)
      worsened before enoxaparin therapy and 6 (4%) worsened after beginning enoxaparin
      use. No differences between operative patient (2/24, 8%) and nonoperative patient
      (4/126, 3%) complications were identified (P =.23). Study group mortality was 7%
      (10/150). All 6 patients who developed progression of IHI after initiation of
      enoxaparin therapy survived hospitalization. A deep vein thrombosis was
      identified in 2 (2%) of 106 patients. CONCLUSION: Enoxaparin can be safely used
      for VTE prophylaxis in trauma patients with IHI when started 24 hours after
      hospital admission or after craniotomy.

PMID- 12049542
TI  - Devastating and fatal complications associated with combined vascular and bile
      duct injuries during cholecystectomy.
AB  - HYPOTHESIS: Multiple centers have reported on bile duct injuries after
      cholecystectomy, but few have reported on the impact of concomitant vascular
      injuries. DESIGN: Twenty-seven life-threatening complex injuries (CIs) (Bismuth
      level III, IV, or V or combined arterial-ductal injuries) were retrospectively
      compared with 22 noncomplex injuries (NCs) (level I or II). SETTING: Tertiary
      referral center. MAIN OUTCOME MEASURES: The incidence and level of biliary and
      arterial injuries and their resulting morbidity and mortality. RESULTS: Bismuth
      classifications of all injuries were as follows: level I in 6 patients (12%), II
      in 19 (39%), III in 12 (24%), IV in 8 (16%), and V in 4 (8%). Diagnosis was based
      on peritonitis (n = 13 [27%]), endoscopic retrograde pancreatography (n = 19
      [39%]), and percutaneous transhepatic cholangiography (n = 7 [14%]). Delayed
      referral was more common in levels I through IV (100 days) than in level V (15
      days) (P<.001). Repairs were attempted in level IV (75%), III (67%), V (25%), and
      II (11%). Thirteen arterial injuries (26%) occurred irrespective of ductal injury
      level: I (n = 1), II (n = 3), III (n = 1), IV (n = 5), and V (n = 3). There was,
      however, a higher incidence of repairs before referral in the CI group (59% vs
      5%; P<.01), with resulting higher rates of complication (70% vs 23%; P<.01). Five
      deaths occurred in the CI group vs 1 in the NC group (P =.14). In univariate
      analysis, the presence of arterial injury vs no arterial injury was a predictor
      of mortality (5 [38%] of 13 patients vs 1 [3%] of 36 patients; P<.001).
      CONCLUSION: Bile duct injuries after cholecystectomy can be morbid and lethal
      with the incidence of arterial injury grossly underestimated.

PMID- 12049543
TI  - Increased rate of infection associated with transfusion of old blood after severe
      injury.
AB  - HYPOTHESIS: Blood components undergo changes during storage that may affect the
      recipient, including the release of bioactive agents, with significant immune
      consequences. We hypothesized that transfusion of old blood increases infection
      risk in severely injured patients. DESIGN: Prospective cohort study. SETTING:
      Urban level I regional trauma center. PATIENTS: Sixty-one trauma patients with an
      Injury Severity Score greater than 15, age older than 15 years, and survival
      longer than 48 hours who were transfused with 6 to 20 U of red blood cells in the
      first 12 hours after injury were studied. By means of blood bank records, the age
      of each unit of blood was determined. INTERVENTION: Transfusion of allogeneic red
      blood cells. MAIN OUTCOME MEASUREMENTS: Major infectious complications. RESULTS:
      The early (<12 hours) transfusion requirement was 12 +/- 0.6 U, with a mean age
      27 +/- 1 days. Major infections developed in 32 patients (52%). Age and Injury
      Severity Score were not significantly different between patients who developed
      infections and those who did not (age, 39 +/- 4 vs 36 +/- 3 years; Injury
      Severity Score, 33 +/- 1.5 vs 29 +/- 1.5). Transfusion of older blood was
      associated with subsequent infection; patients who developed infections received
      11.7 +/- 1.0 and 9.9 +/- 1.0 U of red blood cells older than 14 and 21 days,
      respectively, compared with 8.7 +/- 0.8 and 6.7 +/- 0.08 in patients who did not
      develop infections (both P<.05, t test). Multivariate analysis confirmed age of
      blood as an independent risk factor for major infections. CONCLUSIONS:
      Transfusion of old blood is associated with increased infection after major
      injury. Other options, such as leukocyte-depleted blood or blood substitutes, may
      be more appropriate in the early resuscitation of trauma patients requiring
      transfusion.

PMID- 12049544
TI  - Abdominal seat belt marks in the era of focused abdominal sonography for trauma.
AB  - HYPOTHESIS: Focused abdominal sonography for trauma (FAST) is an unreliable
      method for assessing intra-abdominal injury in patients with seat belt marks.
      DESIGN: Retrospective review of trauma patients with intestinal injury and seat
      belt marks during a 3-year period. Records were reviewed for patient
      demographics, FAST results, computed tomographic (CT) scan results, and operative
      findings. The CT scan results were considered positive if bowel wall thickening,
      extraluminal air, or free fluid without solid organ injury were present. SETTING:
      University hospital designated as a level I trauma center. PATIENTS: Twenty-three
      patients who required operation for intestinal or mesenteric injury and who had
      an abdominal seat belt mark. MAIN OUTCOME MEASURE: Sensitivity of FAST in these
      patients. RESULTS: All patients were evaluated using both FAST and CT scan of the
      abdomen and pelvis. Eighteen patients (78%) had either negative or equivocal FAST
      results when significant intestinal injury was present. All 23 patients had CT
      scan findings suggestive of bowel or mesenteric injury. Moderate-to-large free
      intraperitoneal fluid without solid organ injury was the most common finding (n =
      21, 91%). Operative findings included small-bowel perforation (n = 18, 78%),
      colonic perforation (n = 7, 30%), bowel deserosalization (n = 8, 35%), and
      isolated mesenteric injury (n = 5, 22%). Sixteen patients (70%) had multiple
      intra-abdominal injuries. All patients were taken directly from the emergency
      department to the operating room. Seventeen percent of operative explorations
      (4/23) were nontherapeutic (no repairs required). CONCLUSION: This study confirms
      that FAST cannot reliably exclude intestinal injury in patients with seat belt
      marks.

PMID- 12049545
TI  - Outcomes of laparoscopic Nissen fundoplication in patients with the
      "hypercontractile esophagus".
AB  - HYPOTHESIS: To determine if a hypercontractile esophagus, manifested by high
      amplitude peristaltic contractions (HAPCs) or hypertensive lower esophageal
      sphincter (HLES), affects the outcome of antireflux surgery. DESIGN: Case series.
      Prospectively maintained database. Direct contact with patients. Mean follow-up
      28.7 months. SETTING: University hospital. PATIENTS: Of 643 patients who had
      antireflux surgery for uncomplicated gastroesophageal reflux disease (GERD), 15
      had HAPCs (> or = 150 mm Hg) and 4 HLES (> or = 45 mm Hg). INTERVENTION:
      Laparoscopic Nissen fundoplication in all patients. MAIN OUTCOME MEASURES: (1)
      Frequency of hypercontractile esophagus in patients considered for antireflux
      procedure. (2) Effect of fundoplication on esophageal acid exposure and symptoms.
      (3) Establish whether dysphagia or chest pain develop after fundoplication.
      RESULTS: The typical GERD symptoms of heartburn and/or regurgitation occurred in
      15 (79%) and 13 (69%) of 19 patients. Dysphagia was present in 5 of 15 patients
      with HAPCs and in 0 of 4 with HLES; chest pain was found 5 of 15 patients with
      HAPCs. After fundoplication acid exposure was improved in all (92%, 16/17) but 1
      and was totally normal in 10 patients (83%). Heartburn improved in 11(78%) of 14
      and resolved in 8 patients (57%) of the 14. Chest pain improved in 4 (80%) of the
      5 patients who had it, and developed in 3 (23%) who did not have it
      preoperatively. In patients with HAPCs, dysphagia improved in 4 (80%) of 5
      patients with complete resolution in 3 (60%). New dysphagia developed in 2 (11%)
      of the 19 patients, 1 in each group. No patient with HLES developed chest pain.
      CONCLUSIONS: High-amplitude peristaltic contractions or HLES may be associated
      with GERD in a subset of patients with dysphagia or chest pain. In such patients,
      a Nissen fundoplication, by effectively controlling GERD, relieves these symptoms
      in most patients. A hypercontractile esophagus in patients with GERD should not
      be considered a contraindication to a total fundoplication. The surgeon and the
      patient should be aware of the risk of developing chest pain after the operation.

PMID- 12049546
TI  - Severity scoring for prognostication in patients with severe acute pancreatitis:
      comparative analysis of the Ranson score and the APACHE III score.
AB  - BACKGROUND: Despite a paucity of validation, the Ranson score is still the most
      popular method for gauging the severity of pancreatitis. HYPOTHESES: The Ranson
      score more accurately predicts outcomes in patients with severe acute
      pancreatitis (SAP) when compared with APACHE (Acute Physiology and Chronic Health
      Evaluation) III scores, and the individual components of the Ranson score differ
      in their capacities to predict outcome in patients with SAP. METHODS: Patients
      admitted with SAP to a university surgical intensive care unit (ICU) were studied
      prospectively. Each component and the total Ranson score were recorded. Also
      recorded were the APACHE II and III scores. These Ranson variables were compared
      using univariate analysis of variance for mortality, need for operative
      debridement, and need for an ICU stay for longer than 7 days. Significant
      variables were then analyzed by a multivariate analysis of variance to assess
      independent predictors of mortality, the need for debridement, and prolonged
      length of stay. Data are given as the mean +/- SEM. RESULTS: Seventy-six patients
      (21.1% mortality), aged 61.8 +/- 1.9 years, were studied. The mean APACHE III
      score was 48.2 +/- 3.3, and the mean ICU stay was 10.4 +/- 2.1 days. The number
      of positive Ranson variables was significantly higher in nonsurvivors compared
      with survivors (5.6 +/- 0.5 vs 3.4 +/- 0.2; P<.001), as were the APACHE III score
      (76.9 +/- 9.9 vs 40.5 +/- 2.5; P<.001) and ICU stay (24.9 +/- 7.5 vs 76.5 +/- 1.9
      days; P =.002). Ranson variables that predicted mortality included values for
      blood urea nitrogen, calcium, base deficit, and fluid sequestration. CONCLUSIONS:
      The Ranson score remains a valid predictor of outcomes in patients with SAP, and
      individual Ranson variables determined 48 hours after hospital admission
      predicted adverse outcomes more accurately than early Ranson variables in
      patients with SAP.

PMID- 12049547
TI  - Surgical technique of intraoperative radiotherapy in conservative treatment of
      limited-stage breast cancer.
AB  - At the European Institute of Oncology, Milan, Italy, we have focused our interest
      on the use of intraoperative radiation therapy (IORT) in limited-stage breast
      cancer that is conservatively treated. A new technique to perform IORT was
      applied in 185 patients from July 1, 1999, to October 31, 2001. As the surgeon
      plays a crucial role in this procedure in selecting the patients, performing the
      breast resection, preparing the gland as a target to receive IORT, delivering the
      radiation directly to the mammary gland via a dedicated applicator, and, finally,
      reconstructing the breast, each phase of the surgical technique has been
      completely standardized and is described herein. The use of IORT in the
      conservative treatment of breast cancer could allow the course of external
      fractionated-dose radiation therapy to be completely avoided; IORT dramatically
      reduces radiation exposure of the skin, lung, and subcutaneous tissues and avoids
      the irradiation of the contralateral breast, which contributes to a very low
      incidence of radiation-induced sequelae. In our experience, IORT for limited
      stage breast carcinoma is easy to perform and only briefly prolongs the duration
      of the surgical procedure.

PMID- 12049548
TI  - Image of the month. Gallbladder volvulus.

PMID- 12049550
TI  - Stop the pendulum.

PMID- 12049552
TI  - Cephalic vein cutdown approach for long-term indwelling central venous access.

PMID- 12049553
TI  - Important technical considerations for skin-sparing mastectomy with sentinel
      lymph node dissection.

PMID- 12049554
TI  - John Wyeth (1845-1922) and the postgraduate education and training of America's
      surgeons.

PMID- 12049555
TI  - Randomized controlled trials for evaluating surgical questions.
AB  - OBJECTIVE: To discuss some of the obstacles inherent in the design of the
      randomized controlled trial (RCT) that the surgeon must confront and options to
      minimize these obstacles. DATA SOURCES: The literature was searched for articles
      discussing RCTs using MEDLINE from 1966 to 1998. STUDY SELECTION: Studies
      relevant to the general use of RCTs for evaluating surgical questions were
      selected. SYNTHESIS: Several problems inherent in RCTs were noted: (1) ethical
      considerations, (2) difficulties in patient accrual, (3) patient preferences, and
      (4) variability in surgical proficiency/technique. Some means of minimizing these
      problems are (1) the concept of clinical equipoise, (2) multicenter trials, and
      (3) stratified sampling of patients. Alternatives to the classic RCT are
      discussed, namely, the randomized consent design and the patient preference
      design. CONCLUSIONS: The nature of the RCTs is that they are difficult to use to
      evaluate surgical techniques. Some options are available to minimize these
      difficulties. Designing and conducting RCTs to evaluate surgical interventions
      require careful planning and some compromises. Unless the previously mentioned
      criteria are applied, the validity of the RCT can be considered no greater than
      that of other trials.

PMID- 12049556
TI  - Characteristics of olfactory disorders in relation to major causes of olfactory
      loss.
AB  - OBJECTIVE: To investigate the consequences of olfactory loss and explore specific
      questions related to the effect of duration of olfactory loss, degree of
      olfactory sensitivity, and cause of the olfactory loss. PATIENTS: A total of 278
      consecutive patients with hyposmia or anosmia were examined. RESULTS: Causes of
      olfactory loss were categorized as follows: trauma (17%), upper respiratory tract
      infection (URI) (39%), sinonasal disease (21%), congenital anosmia (3%),
      idiopathic causes (18%), or other causes (3%). Our data suggest that (1) recovery
      rate was higher in URI olfactory loss than in olfactory loss from other causes;
      (2) likelihood of recovery seemed to decrease with increased duration of
      olfactory loss; and (3) the elderly are more prone to URI olfactory loss than
      younger patients. Regarding changes in quality of life (QoL), we found that (1)
      in most patients olfactory loss caused food-related problems; (2) loss in QoL did
      not change with duration of olfactory loss; (3) younger patients had more
      complaints than older ones, and women had more complaints than men; (4) complaint
      scores were higher in hyposmic patients than in anosmic patients; and (5) self
      rated depression did not relate to measured olfactory function. CONCLUSIONS:
      Among many complaints of olfactory loss, the predominant ones were food related.
      This loss in QoL seemed to be of greater importance in younger than in older
      people, and women seem to be affected more strongly than men.

PMID- 12049557
TI  - Long-term follow-up of surgically treated phantosmia.
AB  - OBJECTIVES: To determine whether transnasal excision of olfactory epithelium is a
      safe, effective therapy and to learn more of the pathogenesis of phantosmia by
      studying the histological features of the excised mucosa. DESIGN: A retrospective
      study consisting of a medical record review and telephone survey. Follow-up
      ranged from 1 to 11 years (average, 5.4 years). Excised tissues were
      histologically processed and descriptively compared with normal and other
      abnormal olfactory tissues. SETTING: Tertiary university medical referral
      centers. PATIENTS: All patients who presented to the primary author (D.A.L.) from
      1988 to 1999 with unremitting phantosmia lasting longer than 4 years.
      INTERVENTION: Olfactory testing and transnasal endoscopic excision of olfactory
      mucosa. MAIN OUTCOME MEASURES: Tested olfactory function, patients' perception of
      phantom odor resolution, and histological findings. RESULTS: Of 8 patients, 7
      have complete and permanent resolution of their phantosmia. Postoperatively, the
      single nostril olfactory ability in the operated-on nostril is decreased in 2
      nostrils, remains unchanged in 7, and is improved in 1. The excised olfactory
      mucosa generally shows a decreased number of neurons, a greater ratio of immature
      to mature neurons, and disordered growth of axons with some intraepithelial
      neuromas. CONCLUSIONS: Surgical excision of olfactory epithelium is an effective
      and safe method to relieve phantosmia while potentially preserving olfactory
      ability. The abnormal histological features of the excised olfactory tissue
      suggest at least some pathological condition in the peripheral olfactory system.
      This nasal surgery requires intensive olfactory evaluation and follow-up. It is
      also extremely difficult with significant risks, and therefore should be limited
      to specialized centers.

PMID- 12049558
TI  - Long-term results of olfaction rehabilitation using the nasal airflow-inducing
      ("polite yawning") maneuver after total laryngectomy.
AB  - OBJECTIVES: To study the long-term results of the nasal airflow-inducing maneuver
      (NAIM) as an olfaction rehabilitation tool after laryngectomy and to investigate
      the effectiveness of a new, simpler odor detection test (ODT) called the smell
      disk test (SDT), or Zurcher Geruchstest. DESIGN: Intervention study. SETTINGS:
      National cancer center. PATIENTS: Forty-one laryngectomees who received olfaction
      rehabilitation training with the NAIM 4 months to 2 years earlier. This so-called
      polite yawning maneuver creates an "underpressure" in the oral cavity, which, in
      turn, generates a nasal airflow that enables odor molecules to again reach the
      olfactory epithelium. MAIN OUTCOME MEASURES: Olfaction acuity testing with a
      standard ODT, along with a questionnaire, providing a subjective olfaction score
      (present odor perception scale [POPS]), and the SDT, as well as assessment of the
      patients' correct execution of the NAIM by speech-language pathologists on video
      recordings made during odor testing and long-term assessment of olfaction acuity.
      RESULTS: The correlation between the previously used ODT-POPS combination and the
      SDT was kappa = 0.56 (P<.001). Based on these results, we preferred to use the
      much simpler SDT instead of the laborious combination of the ODT-POPS. Based on
      the SDT results, 19 (46%) of the 41 laryngectomees were "smellers" and could be
      considered normosmic. There was a significant relationship (P =.03) between the
      patient's correct execution of the NAIM and whether or not the laryngectomee was
      a smeller according to the SDT. CONCLUSIONS: The effectiveness of the NAIM, or so
      called polite yawning technique, for the rehabilitation of olfaction in
      individuals who have undergone total laryngectomy was reconfirmed. Long-term
      olfaction rehabilitation was achieved in about 50% of the patients, but more
      intensified training may be needed to increase the percentage of successfully
      rehabilitated individuals. The SDT is an effective and simple test for the
      assessment of olfaction acuity after laryngectomy.

PMID- 12049559
TI  - Pediatric head and neck malignancies: US incidence and trends over 2 decades.
AB  - BACKGROUND: Recent reports have noted an increase in the overall incidence of
      pediatric cancer. OBJECTIVE: To determine whether this trend is applicable to
      malignancies of the head and neck in children. DESIGN: Using the National Cancer
      Institute's Surveillance, Epidemiology, and End Results tumor database, we
      determined the incidence of all cancers diagnosed from 1973 through 1996 in
      children younger than 19 years. This was compared with the incidence of head and
      neck malignancies within the same population. Rates were then determined for
      eight 3-year periods from 1973-1975 to 1994-1996 and adjusted by use of three 5
      year age groups weighted by the 1970 US standard population. RESULTS: A total of
      24,960 malignancies diagnosed in children younger than 19 years were identified
      for the study period. From this group, 3050 tumors (12%) were located in the head
      and neck. The average annual rate of all cancer (number of malignancies per
      100,000 person-years) in children younger than 15 years rose 25% from 11.22 (95%
      confidence interval [CI], 10.70-11.74) for 1973-1975 to 14.03 (95% CI, 13.46
      14.60) for 1994-1996. Among malignancies of the head and neck, the incidence rate
      increased 35% from 1.10 (95% CI, 0.94-1.26) to 1.49 (95% CI, 1.30-1.68) during
      the same period. CONCLUSION: The incidence of head and neck malignancies among
      children younger than 15 years in the United States from 1973 through 1996
      increased at a greater rate than childhood cancer in general.

PMID- 12049560
TI  - Suppurative complications of acute otitis media in the era of antibiotic
      resistance.
AB  - OBJECTIVE: To review our experience with suppurative complications of acute
      otitis media (AOM) in the era of antibiotic resistance, given a perceived
      increase in the number of such cases in recent years requiring surgical
      intervention. DESIGN: Retrospective review of pediatric patients presenting with
      suppurative complications of AOM from January 1993 to June 2000. SETTING:
      Academic tertiary care children's medical center. PATIENTS: A total of 90
      pediatric patients, ranging in age from 3 months to 16 years (mean age, 45
      months). RESULTS: A total of 104 suppurative complications of AOM occurred in 90
      patients over the 7.5-year study period. The incidence of noncoalescent,
      coalescent, and total cases of mastoiditis and total number of suppurative
      complications all increased over the study period, with coalescent outpacing
      noncoalescent disease during the last 3 years of the study. A trend toward an
      increasing number of cases requiring surgical intervention was noted during the
      study period, corresponding to an increasing number of resistant Streptococcus
      pneumoniae isolates. Ten of 16 S pneumoniae isolates were resistant, primarily
      collected from younger children ranging in age from 4 to 24 months (mean age,
      11.9 months). CONCLUSION: The rising incidence of resistant S pneumoniae
      corresponded to the increasing number of suppurative complications of AOM during
      the study period and seemed to contribute to more aggressive infectious processes
      requiring surgical intervention.

PMID- 12049561
TI  - Major and minor temporal bone abnormalities in children with and without
      congenital sensorineural hearing loss.
AB  - OBJECTIVE: To determine the extent of correlation between sensorineural hearing
      loss (SNHL) and abnormal temporal bone anatomy in children. DESIGN: Axial and
      coronal high-resolution computed tomographic scans of the temporal bones of 247
      children (494 ears) aged 2 months to 15 years with and without SNHL were blindly
      reviewed. The presence or absence of mild or severe cochlear dysplasias,
      vestibular dysplasias, and an enlarged vestibular aqueduct (VA) were recorded.
      The width of the VA was measured. The height, width, and length of the internal
      auditory canal (IAC) were measured, and abnormalities were described as narrow,
      widened, or bulbous. Clinical information was then reviewed to determine the
      presence or absence of a congenital syndrome and/or SNHL, and historical factors
      that might be responsible for SNHL. MAIN OUTCOME MEASURE: The relationship
      between radiographic findings and SNHL. RESULTS: One hundred thirteen patients
      (185 ears) had SNHL. Significant abnormal temporal bone anatomy in children with
      vs without SNHL included major cochlear and vestibular dysplasias (17% vs 0%;
      P<.001), enlarged VA (>2 mm) (5% vs 0%; P<.001), and narrow IAC (< or =2 mm) (4%
      vs 1%; P=.03). The average IAC width (4.85 vs 5.02 mm), height (4.39 vs 4.62 mm),
      and length (11.22 vs 11.44 mm) were not statistically different between children
      with vs without SNHL. In children with vs without SNHL, neither a widened (0.5%
      vs 3.6%) nor a bulbous (9% vs 8%) IAC was seen more often in children with SNHL.
      In ears with SNHL, the presence of a congenital syndrome significantly increased
      the risk of cochlear and vestibular abnormalities of the temporal bone (45% vs
      14%; P<.001), including IAC abnormalities (30% vs 2%;P<.001), which overall were
      more commonly seen in children with (20%) vs without (3%) a congenital syndrome
      regardless of the presence of SNHL. No children with an enlarged VA had a
      congenital syndrome. CONCLUSIONS: Well-established temporal bone abnormalities
      such as cochlear and vestibular abnormalities and a grossly enlarged vestibular
      aqueduct are significantly found in children with SNHL. A narrow IAC is found
      more often in children with vs without SNHL. No significant correlation is found
      between SNHL and radiographic findings of a widened or bulbous IAC. In children
      with a congenital syndrome, more IAC abnormalities were seen, regardless of the
      presence of SNHL. In children with SNHL, the presence of a congenital syndrome
      increases the likelihood of a cochlear or vestibular abnormality.

PMID- 12049562
TI  - Tonsillectomy by means of plasma-mediated ablation: prospective, randomized,
      blinded comparison with monopolar electrosurgery.
AB  - OBJECTIVE: To compare plasma-mediated ablation (PMA) with monopolar
      electrosurgery (MES) for pediatric tonsillectomy. DESIGN: Prospective,
      randomized, blinded study. SETTING: Academic children's hospital. PARTICIPANTS:
      Thirty-four children, aged 4 to 7 years. INTERVENTIONS: Tonsillectomy by means of
      PMA (n = 17) or MES (n = 17). OUTCOME MEASURES: We measured surgical efficacy,
      estimated blood loss, and surgical time during tonsillectomy and morphine use,
      immediate postoperative pain, and recovery scores after tonsillectomy. Parents
      recorded recovery of normal diet and activity and their own return to work for 10
      days after surgery. Histopathologic evaluation of excised tonsils was performed.
      We reviewed medical records and attempted follow-up telephone contact. RESULTS:
      With no significant difference in blood loss compared with MES, PMA was effective
      for tonsillectomy. Performance of PMA took longer (24 vs 16 minutes; P =.002).
      Results of histopathologic evaluation showed less thermal injury with PMA than
      with MES (P =.03). Morphine consumption, pain, and recovery scores were
      equivalent between groups. We found no significant difference in recovery of
      normal diet and activity or parental return to work. Patients undergoing PMA had
      a greater number of perioperative complications than those undergoing MES,
      including 2 patients in the PMA group (compared with none in the MES group) who
      required unplanned admission for postoperative airway obstruction. CONCLUSIONS:
      Plasma-mediated ablation for pediatric tonsillectomy resulted in less
      histopathologic thermal injury than MES, but did not show a statistically faster
      recovery to normal activity and diet or parental return to work. In addition, PMA
      took longer to perform, and had more complications. Therefore, PMA should not
      replace MES for pediatric tonsillectomy. The reduced thermal injury with PMA
      supports investigation into other means of using plasma ablation to treat
      tonsillar hypertrophy.

PMID- 12049563
TI  - Steroid inhaler laryngitis: dysphonia caused by inhaled fluticasone therapy.
AB  - OBJECTIVE: To describe a condition that is referred to as steroid inhaler
      laryngitis, a clinical entity that is caused by the use of inhaled fluticasone
      propionate and manifested by dysphonia, throat clearing, and fullness. DESIGN:
      Case series. SETTING: An outpatient clinic of an academic referral center.
      PATIENTS: The study population consisted of 20 patients with reactive airway
      disease and dysphonia who were receiving inhaled fluticasone therapy and who were
      diagnosed as having steroid inhaler laryngitis during the period from January
      1998 to June 2000. INTERVENTION: Cessation of inhaled fluticasone therapy when
      possible, as well as treatment of other underlying causes of dysphonia, such as
      laryngopharyngeal reflux and infectious processes. MAIN OUTCOME MEASURE: The
      resolution of dysphonia with cessation of inhaled fluticasone therapy. RESULTS:
      Patients with steroid inhaler laryngitis were found to have laryngeal findings
      ranging from mucosal edema, erythema, and thickening to leukoplakia, granulation,
      and candidiasis. Patients with more severe mucosal findings were more likely to
      have laryngopharyngeal reflux as well. Resolution of dysphonia occurred only
      after discontinuation of the inhaled fluticasone therapy. CONCLUSIONS: Steroid
      inhaler laryngitis is a form of chemical laryngopharyngitis induced by topical
      steroid administration. Symptoms and physical findings mimic laryngopharyngeal
      reflux, but only respond completely to discontinuation of the inhaled steroid
      therapy. The otolaryngologist should be familiar with this cause of dysphonia.

PMID- 12049564
TI  - The role of woodstoves in the etiology of nasal polyposis.
AB  - OBJECTIVE: To determine the role of environmental pollutants in the etiology of
      nasal polyposis. DESIGN: Case-control study. SETTING: A community-based hospital
      practice in the Gaspesian peninsula in rural northeastern Quebec. PATIENTS: Fifty
      five case patients with nasal polyposis and 55 age-matched control subjects
      without nasal polyposis who were seen at one physician's practice (J.K.) from
      March 1, 1998, to December 19, 1998. INTERVENTIONS: Exposure to woodstoves,
      indoor tobacco smoke, and pets and occupational exposures to noxious inhalant
      compounds. RESULTS: Forty-five (82%) of the cases, but only 14 (25%) of the
      controls, reported using woodstoves, yielding a crude odds ratio (OR) of 13.1.
      The corresponding risk associated with occupational exposure to noxious inhalant
      compounds was also high (OR, 6.1). When adjusted in various ways for the presence
      of other factors, these ORs remained high and statistically significant. For
      woodstove use, the point estimates of the ORs were consistently above 10, with
      the lower limits of 95% confidence intervals above 5. For occupational exposures
      to noxious inhalant compounds, the various adjusted OR estimates were above 6,
      with the lower limits above 1.5. CONCLUSIONS: There is a strong association
      between the use of woodstoves as a principal source of heating and the
      development of nasal polyposis. Occupational exposures to noxious inhalant
      compounds (other than tobacco smoke) also play an important role in its etiology.

PMID- 12049565
TI  - Success and predictability of provox prosthesis voice rehabilitation.
AB  - OBJECTIVES: To determine the success rate and relating clinical factors of voice
      prosthesis rehabilitation and to analyze the discrimination ability of the
      multidimensional Harrison-Robillard-Shultz Tracheoesophageal Puncture Rating
      Scale (HRS Rating Scale). DESIGN: Prospective clinical study. SETTING: University
      Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital
      Inselspital, Bern, Switzerland. SUBJECTS AND METHODS: From 1992 through 1998, 87
      patients with advanced squamous cell carcinoma of the larynx and/or hypopharynx
      underwent primary tracheoesophageal puncture after total laryngectomy. Clinician
      otolaryngologists and speech/language pathologists independently used the HRS
      Rating Scale for success assessment of voice prosthesis rehabilitation. RESULTS:
      Age, sex, tumor localization, tumor stage, and radiation therapy had no influence
      on the success of voice prosthesis rehabilitation. Overall, voice rehabilitation
      success rates between 40% and 62% were achieved. Speech/language pathologists and
      clinician otolaryngologists evaluated the same patient group without significant
      statistical differences. The HRS Rating Scale analysis showed an equal
      distribution of the subscale parameter care in functional and nonfunctional
      speakers and a strong correlation between the subscale parameters quality and
      use. CONCLUSIONS: Because of its safety and simplicity, tracheoesophageal
      puncture has become a state of the art method for voice rehabilitation after
      total laryngectomy. The short-term superiority of voice prosthesis in voice
      rehabilitation over esophageal speech rehabilitation must be seen in light of
      comparable long-term success rates of the 2 methods.

PMID- 12049566
TI  - Fiberoptic examination of the pharyngoesophageal segment in tracheoesophageal
      speakers.
AB  - OBJECTIVE: To describe a novel use of flexible fiberoptic endoscopy to examine
      the pharyngoesophageal segment, upper esophagus, and distal end of the
      tracheoesophageal prosthesis in patients who have undergone a total laryngectomy
      and a tracheoesophageal puncture. METHODS: Five patients with poor-quality or no
      tracheoesophageal voice were evaluated by a speech pathologist and an
      otolaryngologist. A flexible endoscope interfaced with a video monitoring device
      was introduced transnasally and passed through the pharyngoesophageal segment.
      Examination of the anatomical relationship between the prosthesis and the
      esophageal mucosa was conducted while the subjects attempted to phonate.
      Treatments were then initiated based on the endoscopic findings. CONCLUSION:
      Flexible endoscopy is a safe, cost-effective, diagnostic tool for evaluating
      laryngectomees suffering from poor-quality tracheoesophageal voice.

PMID- 12049567
TI  - Estimating DNA repair by sequential evaluation of head and neck tumor radiation
      sensitivity using the comet assay.
AB  - BACKGROUND: The alkaline comet assay is a microelectrophoretic technique for
      detecting single-strand DNA breaks, and may be used as an indirect measure of
      hypoxia by determining the radiation sensitivity of individual cells. OBJECTIVE:
      To assess the ability of the comet assay to estimate the rate of DNA repair after
      irradiation in patients with head and neck cancer. METHODS: The comet assay was
      used to evaluate DNA damage in fine-needle aspirates of lymph nodes containing
      metastatic squamous cell carcinoma in patients with head and neck cancer 1, 2,
      and 3 minutes after treatment with 500 rad (5 Gy) of irradiation. The amount of
      DNA damage (measured as the "tail moment" of the comet) is proportional to the
      number of DNA single-strand breaks after irradiation, which in turn depends on
      the oxygen concentration in each cell. RESULTS: The mean +/- SD of the median
      tail moment of the 1-minute postirradiation comets was 29.4 +/- 14.2 (n = 27).
      After 2 minutes, the mean median tail moment decreased to 25.4 +/- 13.6 (n = 25),
      representing a mean decrease of 11.9% in those patients with both 1- and 2-minute
      comet assays. Assuming a linear rate of repair, this decrease in DNA damage
      corresponds to a repair half-life of 4.2 minutes. A 3-minute assay was also
      performed on samples from a smaller number of patients (n = 9), with a mean value
      not significantly different from that of the 2-minute assay of the samples from
      this group. CONCLUSIONS: The comet assay is a promising tool for evaluating
      radiation sensitivity in individual cells. The rate of DNA repair early after
      irradiation is consistent with data in the literature.

PMID- 12049568
TI  - Positron emission tomography in the evaluation of synchronous lung lesions in
      patients with untreated head and neck cancer.
AB  - BACKGROUND: Positron emission tomography (PET) with the glucose analogue
      fludeoxyglucose F 18 uses the increased glucose uptake that is observed in
      neoplastic cells. It can differentiate between benign and malignant pulmonary
      lesions in patients with lung tumors. Applications of PET in extracranial head
      and neck neoplasms have included evaluating patients with unknown primary
      lesions, detecting primary and recurrent head and neck tumors, monitoring
      response to radiotherapy, and evaluating the N0 neck in oral cavity carcinomas.
      Its role in determining the presence of synchronous lung lesions has not been
      defined. PATIENTS AND METHODS: A retrospective review of 115 patients who
      underwent PET between October 1994 and October 1996 was performed to evaluate
      extracranial head and neck neoplasms. Fifty-nine (51%) previously untreated
      patients with squamous cell carcinoma of the upper aerodigestive tract were
      analyzed. RESULTS: Fifteen patients (25%) had PET scans that were positive for
      synchronous lung lesions. Five patients had a disease process that did not
      warrant further investigation; they did not have pathological confirmation of
      their lung lesions. Of these, 3 died of disease within 2 months of the diagnosis
      of primary head and neck squamous cell carcinoma, 1 was unavailable for follow
      up, and 1 had lung lesions that were considered metastatic and no pathological
      confirmation of lung lesions was obtained. The remaining 10 patients with
      positive PET scan findings were investigated further: 8 patients had biopsy
      confirmed lung lesions; 5 patients had positive findings on chest x-ray films; 8
      had positive findings on computed tomographic scans; and 3 had positive findings
      on bronchoscopy. The results of 2 PET scans were false-positive. The PET scans
      were important in altering treatment in 3 patients; of these, 3 had negative
      findings on chest x-ray films, 2 had positive findings on computed tomographic
      scans, and 1 had positive findings on bronchoscopy. CONCLUSIONS: The overall
      sensitivity, positive predictive value, and accuracy of PET were 100%, 80%, and
      80%, respectively. The overall accuracy of radiography of the chest, computed
      tomography of the chest, and bronchoscopy was 70%, 90%, and 50%, respectively.
      The accuracy of PET over bronchoscopy was statistically significant (P<.05). PET
      appears to be a promising imaging modality for the detection of synchronous lung
      lesions in patients with negative findings on chest x-ray films.

PMID- 12049569
TI  - Enhancement of cytarabine sensitivity in squamous cell carcinoma cell line
      transfected with deoxycytidine kinase.
AB  - BACKGROUND: Cytarabine is the most effective agent known for the treatment of
      acute myeloid leukemia. Its antitumor effect is expressed by combining with DNA
      during replication and then destroying the DNA chain. However, cytarabine has
      only limited activity against most solid tumors, including squamous cell
      carcinoma of the head and neck. The reason for this is thought to be that in cell
      lines of solid tumors the expression of cytidine deaminase, an enzyme that
      degrades cytarabine, is high, whereas the expression of deoxycytidine kinase
      (dCK), which phosphorylates cytarabine (a prodrug), is weak. OBJECTIVE: To
      determine whether head and neck squamous cell carcinomas can be made more
      sensitive to the cytotoxic effects of cytarabine by shifting the balance from the
      degradative to the activation pathway. METHODS: Human SCC-25 squamous carcinoma
      cells were transfected by either retroviral vector or adenoviral vector
      containing DCK gene and were identified for dCK expression by Northern blot
      analysis. In vitro cytotoxic assay after cytarabine exposure was performed using
      these cells. RESULTS: Both retroviral and adenoviral vector-mediated transduction
      of the dCK complementary DNA resulted in marked sensitization of tongue squamous
      carcinoma cell lines to the cytotoxic effects of cytarabine in vitro. CONCLUSION:
      The dCK-cytarabine system may be a useful approach for gene therapy of squamous
      cell carcinomas of the head and neck.

PMID- 12049570
TI  - Ectopic cervical thymus: an uncommon diagnosis in the evaluation of pediatric
      neck masses.
AB  - Ectopic cervical thymic tissue is an uncommon cause of neck masses in children,
      with fewer than 100 cases reported in children who presented with primary neck
      masses. To illustrate the unique characteristics of these tumors, we report the
      case of a 13-month-old boy with ectopic thymic tissue presenting with
      asymptomatic, bilateral, and solid cervical masses. This case report highlights
      several unique findings: (1) the rare nature of solid thymic tumors compared with
      cystic lesions, (2) the utility of magnetic resonance imaging scanning with and
      without fat suppression for diagnosis, and (3) the risks of surgical removal of
      thymic tissue in children. Despite its infrequent occurrence and often
      asymptomatic presentation, ectopic cervical thymus masses should be included as a
      rare cause of cervical masses in the pediatric population. Awareness of this
      diagnosis will allow for appropriate preoperative diagnostic studies, which may
      preclude the need for biopsy.

PMID- 12049571
TI  - Central mucoepidermoid carcinoma of the mandible: tumorigenesis within a
      keratocyst.

PMID- 12049572
TI  - Pathology quiz case. Heterotopic neuroglial tissue (nasal glioma).

PMID- 12049573
TI  - Radiology quiz case. Epidermal inclusion cyst with intracystic keratin debris.

PMID- 12049574
TI  - The Ocular Hypertension Treatment Study: a randomized trial determines that
      topical ocular hypotensive medication delays or prevents the onset of primary
      open-angle glaucoma.
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is one of the leading causes of
      blindness in the United States and worldwide. Three to 6 million people in the
      United States are at increased risk for developing POAG because of elevated
      intraocular pressure (IOP), or ocular hypertension. There is no consensus on the
      efficacy of medical treatment in delaying or preventing the onset of POAG in
      individuals with elevated IOP. Therefore, we designed a randomized clinical
      trial, the Ocular Hypertension Treatment Study. OBJECTIVE: To determine the
      safety and efficacy of topical ocular hypotensive medication in delaying or
      preventing the onset of POAG. METHODS: A total of 1636 participants with no
      evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24
      mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye
      were randomized to either observation or treatment with commercially available
      topical ocular hypotensive medication. The goal in the medication group was to
      reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less. MAIN
      OUTCOME MEASURES: The primary outcome was the development of reproducible visual
      field abnormality or reproducible optic disc deterioration attributed to POAG.
      Abnormalities were determined by masked certified readers at the reading centers,
      and attribution to POAG was decided by the masked Endpoint Committee. RESULTS:
      During the course of the study, the mean +/- SD reduction in IOP in the
      medication group was 22.5% +/- 9.9%. The IOP declined by 4.0% +/- 11.6% in the
      observation group. At 60 months, the cumulative probability of developing POAG
      was 4.4% in the medication group and 9.5% in the observation group (hazard ratio,
      0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of
      increased systemic or ocular risk associated with ocular hypotensive medication.
      CONCLUSIONS: Topical ocular hypotensive medication was effective in delaying or
      preventing the onset of POAG in individuals with elevated IOP. Although this does
      not imply that all patients with borderline or elevated IOP should receive
      medication, clinicians should consider initiating treatment for individuals with
      ocular hypertension who are at moderate or high risk for developing POAG.

PMID- 12049575
TI  - The Ocular Hypertension Treatment Study: baseline factors that predict the onset
      of primary open-angle glaucoma.
AB  - BACKGROUND: The Ocular Hypertension Treatment Study (OHTS) has shown that topical
      ocular hypotensive medication is effective in delaying or preventing the onset of
      primary open-angle glaucoma (POAG) in individuals with elevated intraocular
      pressure (ocular hypertension) and no evidence of glaucomatous damage. OBJECTIVE:
      To describe baseline demographic and clinical factors that predict which
      participants in the OHTS developed POAG. METHODS: Baseline demographic and
      clinical data were collected prior to randomization except for corneal thickness
      measurements, which were performed during follow-up. Proportional hazards models
      were used to identify factors that predicted which participants in the OHTS
      developed POAG. RESULTS: In univariate analyses, baseline factors that predicted
      the development of POAG included older age, race (African American), sex (male),
      larger vertical cup-disc ratio, larger horizontal cup-disc ratio, higher
      intraocular pressure, greater Humphrey visual field pattern standard deviation,
      heart disease, and thinner central corneal measurement. In multivariate analyses,
      baseline factors that predicted the development of POAG included older age,
      larger vertical or horizontal cup-disc ratio, higher intraocular pressure,
      greater pattern standard deviation, and thinner central corneal measurement.
      CONCLUSIONS: Baseline age, vertical and horizontal cup-disc ratio, pattern
      standard deviation, and intraocular pressure were good predictors for the onset
      of POAG in the OHTS. Central corneal thickness was found to be a powerful
      predictor for the development of POAG.

PMID- 12049576
TI  - Phototherapeutic keratectomy for anterior basement membrane dystrophy after laser
      in situ keratomileusis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of phototherapeutic keratectomy
      (PTK) in the treatment of symptomatic anterior basement membrane dystrophy
      following laser in situ keratomileusis (LASIK). METHODS: In a retrospective
      study, 10 eyes of 10 patients that developed symptomatic anterior basement
      membrane dystrophy following LASIK for myopia were treated with PTK using the
      VISX S2 (VISX Inc, Santa Clara, Calif) excimer laser. Primary outcome
      measurements including corneal clarity, resolution of symptoms, uncorrected
      visual acuity (UCVA), manifest refraction, best spectacle-corrected visual acuity
      (BSCVA), and complications were evaluated preoperatively, 1 day postoperatively,
      and at the last postoperative follow-up visit. RESULTS: At the last follow-up
      visit (mean [SD], 8.8 [5.5] months; range, 4-22 months), 100% of the eyes had
      clear corneas with no evidence of anterior basement membrane dystrophy, and all
      eyes were asymptomatic. Mean spherical equivalent changed from -0.75 (0.99)
      diopters (D) (range, -2.75 to +0.25 D) preoperatively to -0.51 (0.80) D (range, 
      1.63 to +1.00 D) at the last follow-up visit (P =.64). Uncorrected visual acuity
      improved from 20/20 or better in 1 eye (10%) and 20/40 or better in 5 eyes (50%)
      preoperatively to 20/20 or better in 5 eyes (50%) and 20/40 or better in 7 eyes
      (70%) postoperatively. No eyes lost lines of BSCVA, 2 eyes gained 1 line, 2 eyes
      gained 2 lines, and 1 eye gained 4 lines. There was a statistically significant
      improvement in mean logMAR BSCVA postoperatively, improving from 0.06 (0.16)
      (range, -0.1 to +0.3) to -0.08 (0.07) (range, -0.1 to +0.1) (P =.04).
      Postoperative complications included diffuse lamellar keratitis that resolved
      after treatment without sequelae (20%) and induced myopia exceeding -1.50 D
      (10%). CONCLUSION: Phototherapeutic keratectomy for the treatment of symptomatic
      anterior basement membrane dystrophy following LASIK treatment is safe and
      effective.

PMID- 12049578
TI  - (Neonatal) retinoblastoma in the first month of life.
AB  - OBJECTIVES: To identify patients with retinoblastoma whose conditions were
      diagnosed at the age of 1 month or younger and to describe their clinical
      features (including ocular and patient survival) and the development of second
      nonocular tumors. MATERIALS AND METHODS: A retrospective study of 1831 patients.
      The cumulative incidence of second cancer development was analyzed using the
      Kaplan-Meier method. RESULTS: Forty-six patients were identified as having a
      diagnosis of retinoblastoma at the age of 1 month or younger (mean age, 18.5
      days). Family history (31 patients [67%]) exceeded leukocoria (6 patients [13%])
      as the most common reason for detection. Twenty-six (56%) of the 46 patients were
      seen with unilateral retinoblastoma, with 22 ultimately developing cancer in the
      fellow eye. At the initial diagnosis, 81 (85%) of the 95 tumors were detected in
      zones 1 and 2. Eighty-two (93%) of the 88 subsequent tumors were located in zones
      2 and 3. In the 26 patients who had unilateral retinoblastoma, 16 of the
      initially affected eyes and 21 of the fellow eyes were salvaged. In the 19 (44%)
      of 20 patients who were seen initially with bilateral retinoblastomas, 31 (82%)
      of the 38 eyes were salvaged. The mean follow-up was 10.9 years. The incidence of
      second nonocular cancers reached 54% by 23.7 years for the patients who received
      radiation therapy, while the incidence was 0% for the patients who did not. Four
      (8.7%) of the 46 patients developed metastatic disease and died; 3 of these
      patients had documented metastases in the first month of life (one at birth).
      CONCLUSIONS: The most common manifesting sign of children diagnosed as having
      retinoblastoma in the first month of life is family history. Eyes with Reese
      Ellsworth group I retinoblastomas were the most common. In patients with
      bilateral and unilateral retinoblastoma, new (subsequent) ocular tumors developed
      in a centrifugal pattern. Despite an early diagnosis, patients' eyes came to
      enucleation, and metastatic disease and death occurred from ocular metastases. In
      patients who received radiation therapy, the probability of developing second
      nonocular cancer is 54% by 23.7 years; no second cancers developed in patients
      who did not receive radiation therapy.

PMID- 12049577
TI  - Decreased visual acuity associated with cystoid macular edema in neovascular age
      related macular degeneration.
AB  - OBJECTIVE: To determine the prevalence and visual significance of cystoid macular
      edema (CME) in eyes with subfoveal neovascular age-related macular degeneration
      using optical coherence tomography (OCT). MATERIALS AND METHODS: The medical
      records of 61 consecutive patients initially seen with nondisciform subfoveal
      neovascular age-related macular degeneration were retrospectively reviewed. All
      patients underwent fluorescein angiography and OCT imaging. Eyes with
      intraretinal hyporeflective spaces in the macula in the OCT images were
      considered to have CME. RESULTS: Twenty-eight (46%) of 61 eyes demonstrated CME
      on the OCT images. The presence of CME and increased foveal thickness correlated
      with decreased visual acuity, but not with the duration of symptoms. Twenty-six
      (93%) of 28 eyes with CME contained classic choroidal neovascularization, whereas
      16 (48%) of 33 eyes without CME contained classic choroidal neovascularization.
      CONCLUSIONS: Cystoid macular edema is a common finding in patients with choroidal
      neovascularization associated with age-related macular degeneration. The presence
      of CME and foveal thickening is associated with worse visual acuity in these
      patients. Cystoid macular edema is more common with choroidal neovascularization
      containing classic component. The OCT is a useful test to detect the presence of
      CME in these patients since CME may be difficult to identify on fluorescein
      angiogram.

PMID- 12049579
TI  - Three-dimensional high-resolution magnetic resonance imaging of ocular and
      orbital malignancies.
AB  - BACKGROUND: Ultrathin-section 3-dimensional fast spin-echo (3-D FSE) T2-weighted
      imaging is a new magnetic resonance imaging (MRI) technique that we used in the
      evaluation of ocular and orbital malignancies. We evaluated the usefulness of
      this new technique compared with conventional MRI. METHODS: Imaging data from 26
      consecutive patients seen in the Ocular Oncology Unit at the University of
      California-San Francisco were retrospectively reviewed by physicians from the
      ocular oncology and neuroradiology units. For all patients, 3-D FSE T2-weighted
      images (27 scans) were compared with results of conventional MRI and correlated
      with results of computed tomography (CT), A- and B-scan ultrasonography,
      ultrasound biomicroscopy, clinical examinations, and histopathology, when
      available. RESULTS: The 3-D FSE T2-weighted imaging sequence resulted in an
      overall improvement in accuracy of imaging findings in 17 (63%) of our 27 cases
      compared with the standard MRI protocol. The increased resolution led to the
      radiographic detection of additional lesions in 11 (41%) of 27 cases and to an
      increase in confidence in radiographic diagnosis in 6 (22%) of the remaining
      cases. The improved resolution of the 3-D FSE T2-weighted sequence resulted in a
      change of disease management in 3 (60%) of the 5 patients with nonretinoblastoma
      lesions. One hundred percent of active retinoblastoma lesions could be detected
      by means of 3-D FSE and conventional imaging; however, inactive lesions were not
      always detected using conventional imaging. CONCLUSIONS: The 3-D FSE T2-weighted
      sequence offers superior resolution of intraocular and orbital structures
      compared with conventional MRI. It is particularly useful in the evaluation of
      intraocular tumors and the nerve-sheath complex. This new technique contributes
      significantly to improved diagnosis and management in patients with ocular and
      orbital malignancies.

PMID- 12049580
TI  - Ocular malingering: a surprising visual acuity test.
AB  - OBJECTIVE: To describe a visual acuity test for use in identifying psychogenic
      visual impairment and malingering. METHODS: The test contained 32 white plates
      with a black Landolt C printed in the center. The sequence of the 4 alternative
      directions of the C was not predictable. After plate 21, 4 circles were
      interspersed among the remaining plates. The test is administered at a distance
      from which the subject is presumed to be able to recognize the optotypes. He or
      she is requested to identify the direction of the C within 2 seconds, and the
      responses are noted. Two elements were evaluated: (1) The number of correct
      answers was compared with the corresponding value of the distribution function of
      the binomial formula that represents the probability of reaching this rate of
      correct answers by pure chance. (2) The response to the first circle (appearing
      after plate 21) was compared with the responses to the previous 19 Cs. The test
      was administered to 20 volunteer pseudomalingerers and 15 patients believed to be
      true malingerers. RESULTS: Malingering was detected in 14 (74%) of 19 volunteers
      included in the evaluation and in 12 (80%) of 15 patients by too many or too few
      correct answers to the stimuli or by their response to one of the circles.
      CONCLUSIONS: This test is useful in proving malingering. It may also provide
      evidence of a minimum visual recognition acuity within the gross dimension of the
      actual acuity.

PMID- 12049581
TI  - Seoul-type keratoprosthesis: preliminary results of the first 7 human cases.
AB  - OBJECTIVE: To evaluate the clinical efficacy of a newly designed Seoul-type
      keratoprosthesis (S-KPro). METHODS: The S-KPro, which consists of a polymethyl
      methacrylate optic, a skirt (polyurethane or polypropylene), and polypropylene
      haptics, was developed and implanted into 2 unsighted and 5 sighted eyes of 7
      patients. One patient had a chemical burn, another had an ocular pemphigoid, and
      the remainder were diagnosed as having Stevens-Johnson syndrome. The preoperative
      visual acuities ranged from light perception to hand motions. The average follow
      up time was 25.6 months. MAIN OUTCOME MEASURES: We evaluated anatomical
      stability, visual acuity, retinal status, and the visual field. RESULTS: At the
      last follow-up visit, the S-KPro was well placed in 6 patients. The best
      corrected visual acuities of the sighted patients ranged from 20/100 to 20/60 in
      the affected eye. One patient each experienced retinal detachment or
      endophthalmitis. Partial extrusion was found in the patient with glaucoma. A
      retroprosthetic membrane was detected in 1 patient and was treated with an Nd:YAG
      laser. No glaucomatous visual field defects were found in any of the sighted
      patients. CONCLUSIONS: Anatomical success was achieved in 6 of 7 eyes. In 3 of
      the 5 sighted eyes, the S-KPro could rehabilitate corneal blindness not
      correctable with keratoplasty.

PMID- 12049582
TI  - Strabismus in children of birth weight less than 1701 g.
AB  - OBJECTIVE: To prospectively study infants of birth weight less than 1701 g in the
      East Midlands of England in the mid 1980s at 10 to 12 years of age to determine
      the incidence and risk factors for strabismus in children born preterm. METHODS:
      Low-birth-weight children (n = 572) who had been examined during the neonatal
      period were invited for a follow-up visit at age 10 to 12 years; 169 eleven-year
      old schoolchildren born at full term were also recruited (the school cohort).
      RESULTS: Of the original 572 children, 293 consented to further examination.
      There was no significant difference between children who were examined and those
      who were not in terms of birth weight, gestational age, retinopathy of
      prematurity, and cranial ultrasound abnormalities. Compared with the school
      cohort (n = 5 [3.0%]; 95% confidence interval, 1.0%-9.1%), the low-birth-weight
      cohort had a significant increase in the prevalence of strabismus (n = 59
      [20.1%]; 95% confidence interval, 15.9%-25.0%; P<.001). Compared with published
      data, there was a relative increase in the occurrence of exotropia in the low
      birth-weight study cohort. Multivariate analysis, by backward logistic
      regression, indicated that retinopathy of prematurity, birth weight, cerebral
      palsy, anisometropia, and refractive error were all independently associated with
      strabismus (P<.05). CONCLUSIONS: The results of this study confirm the increased
      prevalence of strabismus in a low-birth-weight population. This study also
      provides more detailed information on risk factors and strabismus types.

PMID- 12049583
TI  - How does visual impairment affect performance on tasks of everyday life? The SEE
      Project. Salisbury Eye Evaluation.
AB  - OBJECTIVE: To determine the association between performance on selected tasks of
      everyday life and impairment in visual acuity and contrast sensitivity. METHODS:
      Visual acuity and contrast sensitivity were obtained on a population-based sample
      of 2520 older African American and white subjects. Performance was assessed on
      mobility, daily activities with a strong visual component, and visually intensive
      tasks. Disability was defined as performance less than 1 SD below the mean.
      Receiver operating characteristic curve analyses were used to evaluate the
      sensitivity and specificity of thresholds in acuity and contrast loss for
      determining disability. RESULTS: Both visual acuity and contrast sensitivity loss
      were associated with decrements in function. The relationship of function to the
      vision measures was mostly linear, therefore, receiver operating characteristic
      curves were not helpful in identifying cutoff points for predicting disabilities.
      For mobility tasks, most persons were not disabled until they had significant
      acuity loss (logMAR visual acuity >1.0 or <20/200) or contrast sensitivity loss
      (0.9 log units contrast sensitivity). For heavily visually intensive tasks, like
      reading, visual acuity worse than 0.2 logMAR (20/30) or contrast sensitivity
      worse than 1.4 log units was disabling. CONCLUSIONS: Both contrast sensitivity
      and visual acuity loss contribute independently to deficits in performance on
      everyday tasks. Defining disability as deficits in performance relative to a
      population, it is possible to identify visual acuity and contrast loss where most
      are disabled. However, the cutoff points depend on the task, suggesting that
      defining disability using a single threshold for visual acuity or contrast
      sensitivity loss is arbitrary.

PMID- 12049584
TI  - Human limbal progenitor cells expanded on intact amniotic membrane ex vivo.
AB  - BACKGROUND: The transplantation of human limbal epithelium on amniotic membrane
      as a substrate is a new treatment for limbal stem cell deficiency. Limbal
      epithelial stem cells are characterized by a slow cell cycle and the lack of K3
      keratin and connexin 43 (Cx43), a gap junction protein. We investigated Cx43
      expression, gap junction intercellular communication (GJIC), and proliferative
      activity of limbal epithelium expanded on amniotic membrane. METHODS: Connexin 43
      expression and bromodeoxyuridine (BrdU) incorporation were determined by
      immunohistology. The GJIC was investigated by a scrape-loading dye transfer
      assay. Expression of Cx43 and K3 keratin as well as BrdU-retaining nuclei were
      also analyzed after xenotransplantation in nude mice. RESULTS: Limbal epithelium
      showed mean +/- SD 12.4% +/- 14.5% positive units of Cx43 expression and a low
      BrdU labeling index of 2.4% +/- 0.9% (n = 5), of which the latter was due to slow
      cycling, as proved by its increase to 62.0% +/- 9.5% after continuous BrdU
      labeling for 5 days. Most of the expanded epithelium did not show GJIC (83%),
      significantly more than that grown on plastic (6%; P<.002). Basal cells of the
      stratified epithelium after xenotransplantation did not express Cx43 and K3
      keratin, but their nuclei retained BrdU. CONCLUSION: These results support the
      hypothesis that intact amniotic membrane preferentially preserves and expands
      Cx43-negative, keratin K3-negative, and GJIC-deficient limbal epithelium, a
      phenotype resembling that of stem cell-containing limbal basal epithelial cells
      in vivo. CLINICAL RELEVANCE: Intact amniotic membrane is a suitable substrate for
      bioengineering limbal epithelia for ocular surface reconstruction.

PMID- 12049585
TI  - The distribution of mitochondrial activity in relation to optic nerve structure.
AB  - BACKGROUND: The observation of a buildup of mitochondria at the level of the
      lamina cribrosa in the optic nerve head has traditionally been attributed to
      axoplasmic stasis. However, this region is also the transition zone for
      myelination, resulting in differing energy requirements. OBJECTIVE: To
      investigate the relationship between myelination and mitochondrial activity in
      optic nerve tissue. METHODS: Histological, histochemical, and immunocytochemical
      techniques were used to demonstrate the distribution of myelin, cytochrome-c
      oxidase activity, and laminar structure in human optic nerve tissue. A study of
      rabbit optic nerve and retina and unmyelinated human pituitary stalk was also
      performed. Cytochrome-c oxidase activity in the human optic nerve tissue was
      measured using microphotometry. RESULTS: There was a striking inverse
      relationship between myelination and mitochondrial distribution in all tissue
      studied. Statistical analysis of microphotometric data showed this distribution
      to be highly significant. CONCLUSION: We caution against the previous inference
      of a process of axoplasmic stasis and suggest that, instead, the distribution of
      mitochondria reflects the functional requirement of different regions of the
      ganglion cell axon. CLINICAL RELEVANCE: Optic neuropathy is associated with
      several inherited disorders of mitochondria. We suggest that a fine balance
      exists between energy demand and tissue function in the optic nerve, which may
      explain why optic nerve pathological features are seen in those with
      mitochondrial disease.

PMID- 12049586
TI  - Up-regulation of brain-derived neurotrophic factor expression by brimonidine in
      rat retinal ganglion cells.
AB  - OBJECTIVES: Brimonidine tartrate ophth, an alpha(2)-adrenergic agonist, is widely
      used as an antiglaucoma agent for lowering intraocular pressure. Recent studies
      suggest that brimonidine may be neuroprotective for retinal ganglion cells (RGCs)
      following optic nerve crush injury. Brain-derived neurotrophic factor (BDNF), a
      potent neuroprotective factor present in the RGCs, promotes RGC survival in
      culture and following optic nerve injury. We tested the hypothesis that a
      possible mechanism of brimonidine neuroprotection is through up-regulation of
      endogenous BDNF expression in the RGCs. METHODS: A single dosage of brimonidine
      tartrate ophth solution (0.85-34 microM) was injected intravitreally into Sprague
      Dawley rat eyes. The fellow eyes of each animal were injected with balanced salt
      solution (BSS) and used as control eyes. To determine BDNF messenger RNA
      expression, animal eyes were enucleated and processed for in situ hybridization,
      or retinas were isolated and processed for Northern blot analysis using rat BDNF
      radiolabeled riboprobes. RESULTS: In the control eyes injected with saline, BDNF
      was present in a minority of the RGCs. Two days after brimonidine injection, the
      number of BDNF-positive RGCs was increased from 55% to 166%, depending on
      brimonidine concentrations, when compared with those in the controls. In
      addition, the BDNF signal intensities in individual RGCs were elevated 50% in
      brimonidine-injected eyes compared with control eyes. Northern blot revealed a
      28% increase of BDNF expression in the brimonidine group compared with the
      controls (P <.003). No significant difference was observed in BDNF receptor, trk
      B, expression between brimonidine, or BSS control groups. CONCLUSIONS: A single
      dose of a low concentration of intravitreal brimonidine is sufficient to
      significantly increase endogenous BDNF expression in RGCs. These results suggest
      that brimonidine neuroprotection may be mediated through up-regulation of BDNF in
      the RGCs. The BDNF should be further investigated regarding its role in the
      neuroprotective effects reported with brimonidine. CLINICAL RELEVANCE:
      Brimonidine may be (potentially) used clinically as a neuroprotective agent in
      optic neuropathy, including glaucoma, and ischemic and traumatic optic
      neuropathy.

PMID- 12049587
TI  - Use of eye care and associated charges among the Medicare population: 1991-1998.
AB  - OBJECTIVE: To examine trends in the utilization and cost of eye care in the
      Medicare population. METHODS: Data were obtained from fee-for-service physician
      claims (Part B) from a 5% sample of Medicare beneficiaries 65 years and older.
      Use of eye care services and procedures, frequency of ocular diagnoses, and
      allowed charges were compared for each year from 1991 through 1998. RESULTS: The
      proportion of beneficiaries receiving eye care increased from 41.4% to 48.1%
      during the 8-year period. Part B charges attributable to eye care decreased from
      12.5% to 10.4%, with annual inflation-adjusted charges per beneficiary decreasing
      from 235 dollars to 176 dollars (1998 dollars). The proportion of beneficiaries
      with cataract-related claims increased from 23.4% to 27.3%, accounting for
      approximately 60% of eye care charges each year; beneficiaries with retinal
      disease claims increased from 7.8% to 11.4%, capturing 15.4% of eye care charges
      in 1998, up from 10.7% in 1991; and beneficiaries with glaucoma claims increased
      from 6.8% to 9.5%, accounting for nearly 10% of eye care charges each year.
      CONCLUSIONS: The proportion of the Medicare population receiving eye care
      increased between 1991 and 1998. Nevertheless, eye care costs did not increase,
      primarily because of constraints in charges associated with the management of
      cataract.

PMID- 12049588
TI  - Deep lamellar keratoplasty combined with cataract surgery.
AB  - We used a surgical technique that combines deep lamellar keratoplasty,
      phacoemulsification, and intraocular lens implantation for treating patients with
      cataract and corneal stromal disease. Deep lamellar dissection of the cornea was
      first performed with viscoelastic substances (hyaluronate sodium) until the
      highly transparent Descemet membrane solely remained. We then created a short
      corneal tunnel to perform phacoemulsification with low vacuum and intraocular
      lens implantation. The resilience of the Descemet membrane ensured excellent
      viewing of the whole anterior chamber as well as the surgical conditions of a
      closed system. At the end of surgery, a full-thickness donor button was sutured
      into the recipient bed after its Descemet membrane was stripped. This technique
      was effective in these 4 patients with cataract and dense corneal opacity.

PMID- 12049590
TI  - Do you really need your oblique muscles? Adaptations and exaptations.
AB  - BACKGROUND: Primitive adaptations in lateral-eyed animals have programmed the
      oblique muscles to counterrotate the eyes during pitch and roll. In humans, these
      torsional movements are rudimentary. PURPOSE: To determine whether the human
      oblique muscles are vestigial. METHODS: Review of primitive oblique muscle
      adaptations and exaptations in human binocular vision. RESULTS: Primitive
      adaptations in human oblique muscle function produce rudimentary torsional eye
      movements that can be measured as cycloversion and cyclovergence under
      experimental conditions. The human torsional regulatory system suppresses these
      primitive adaptations and exaptively modulates cyclovergence to facilitate
      stereoscopic perception in the pitch plane. It also recruits the oblique muscles
      to generate cycloversional saccades that preset torsional eye position
      immediately preceding volitional head tilt, permitting instantaneous
      nonstereoscopic tilt perception in the roll plane. CONCLUSIONS: The evolution of
      frontal binocular vision has exapted the human oblique muscles for stereoscopic
      detection of slant in the pitch plane and nonstereoscopic detection of tilt in
      the roll plane. These exaptations do not erase more primitive adaptations, which
      can resurface when congenital strabismus and neurologic disease produce
      evolutionary reversion from exaptation to adaptation.

PMID- 12049589
TI  - Transscleral optical coherence tomography: a new imaging method for the anterior
      segment of the eye.
AB  - OBJECTIVE: To present a new imaging method for the anterior segment of the eye.
      METHODS: Transscleral optical coherence tomographic images were generated in
      healthy volunteers using a slitlamp-adapted prototype equipped with a
      superluminescence diode with an infrared wavelength of 1310 nm. RESULTS: The
      optical coherence tomographic system used allowed penetration of human sclera in
      vivo and high-resolution, cross-sectional imaging of the anterior chamber angle
      and the ciliary body. CONCLUSION: The 1310-nm optical coherence tomographic image
      shows a significant potential as a noninvasive diagnostic tool for the anterior
      segment of the eye.

PMID- 12049591
TI  - Answers from the ocular hypertension treatment study.

PMID- 12049592
TI  - Silicone oil egressing through an inferiorly implanted ahmed valve.

PMID- 12049593
TI  - Lens dislocation in Marfan syndrome: potential role of matrix metalloproteinases
      in fibrillin degradation.

PMID- 12049594
TI  - Histopathological changes following photodynamic therapy in human eyes.

PMID- 12049595
TI  - Mushroom-shaped choroidal recurrence of retinoblastoma 25 years after therapy.

PMID- 12049596
TI  - Cosmetically significant proptosis following a tube shunt procedure.

PMID- 12049597
TI  - Paradoxical intraocular pressure elevation after combined therapy with
      latanoprost and bimatoprost.

PMID- 12049598
TI  - Orbital cellulitis as a late complication of glaucoma shunt implantation.

PMID- 12049599
TI  - Retinitis pigmentosa associated with ectopia lentis.

PMID- 12049600
TI  - Pigmentary retinopathy associated with intravitreal fomivirsen.

PMID- 12049601
TI  - Sequential branch retinal artery occlusions following embolization of an
      intracranial meningioma.

PMID- 12049603
TI  - Choroidal hemangiomas with exudative retinal detachments during pregnancy.

PMID- 12049602
TI  - Bilateral vasoproliferative retinal tumors with identical localization in a pair
      of monozygotic twins.

PMID- 12049604
TI  - Microsporidia-induced sclerouveitis with retinal detachment.

PMID- 12049605
TI  - Unilateral manifestation of melanoma-associated retinopathy.

PMID- 12049606
TI  - A child with venous sinus thrombosis with initial examination findings of
      pseudotumor syndrome.

PMID- 12049607
TI  - Multifocal visual evoked potentials and multifocal electroretinograms in
      papillorenal syndrome.

PMID- 12049608
TI  - Using intravenous diphenhydramine to minimize back pain associated with
      photodynamic therapy with verteporfin.

PMID- 12049610
TI  - The C2A domain of synaptotagmin-like protein 3 (Slp3) is an atypical calcium
      dependent phospholipid-binding machine: comparison with the C2A domain of
      synaptotagmin I.
AB  - The synaptotagmin-like protein (Slp) family consists of an N-terminal Rab27
      binding domain and C-terminal tandem C2 motifs, and although it has been
      suggested to regulate Rab27-dependent membrane trafficking, such as Ca2+
      regulated granule exocytosis in T-lymphocytes [Kuroda, Fukuda, Ariga and
      Mikoshiba (2002) J. Biol. Chem. 277, 9212-9218], little is known about the Ca2+
      binding property of the Slp family. In this study, I demonstrated that the C2A
      domain of Slp3 exhibits Ca(2+)-dependent phospholipid-binding activity similar to
      that of the C2A domain of synaptotagmin I (Syt I) with regard to phospholipid
      selectivity, bivalent cation selectivity and effect of ionic strength. This
      finding was surprising because the C2A domains of other C-terminal-type (C-type)
      tandem C2 proteins require five conserved acidic residues in the putative Ca2+
      binding loops 1 and 3 on the top of the beta-sandwich structure for their Ca2+
      /phospholipid-binding activity, whereas the C2A domain of Slp3 contains only one
      conserved acidic residue in the putative Ca2+-binding loop 1. Site-directed
      mutagenesis and chimaeric analysis of the C2A domains of Syt I and Slp3 showed
      that Glu-336 and Glu-337 in the putative Ca2+-binding loop 1 and polybasic
      sequence (Lys-359, Lys-360 and Lys-361) in the beta-4 strand of the C2 structure
      are crucial for Ca2+-dependent phospholipid-binding activity of the Slp3 C2A
      domain, whereas the similar polybasic sequence in the C2A domain of Syt I is
      dispensable for Ca2+-dependent phospholipid-binding activity. These results
      indicate that the C2A domain of Slp3 is an atypical Ca2+-/phospholipid-binding
      machine, compared with other C-type tandem C2 proteins.

PMID- 12049611
TI  - Effects of mutations at the two processing sites of the precursor for the small
      subunit of ribulose-bisphosphate carboxylase in Chlamydomonas reinhardtii.
AB  - The role of the two processing sites in the precursor of the small subunit (SS)
      of ribulose-1,5-bisphosphate carboxylase/oxygenase (pSS) of Chlamydomonas
      reinhardtii was studied by introducing mutations at the cleavage sites for the
      stromal processing peptidases SPP-1 and SPP-2, which hydrolyse wild-type pSS
      (20.6 kDa) to an intermediate-sized product iSS (18.3 kDa) and to the mature SS
      (16.3 kDa), respectively. The mutations introduced into cDNA resulted in exchange
      of (a) two amino acids flanking processing site 1, or (b) one or (c) both amino
      acids flanking processing site 2. Mutation (a) prevented pSS from being processed
      at site 1 but not from cleavage at site 2. Mutation (c) abolished the action of
      SPP-2 but not SPP-1. When pSS with mutation (c) was imported into isolated
      chloroplasts, iSS accumulated while SS formation was abolished. However, mature
      SS was produced even in the absence of iSS synthesis (mutation a). Import of pSS
      bearing mutation (b), which only partially inhibited processing at the SPP-2
      site, slowed the rate of SS formation down whereas iSS and some slightly smaller
      derivatives accumulated. These experiments suggested that in Chlamydomonas
      processing of pSS can occur in two steps, whereby the first step is facultative.
      The same three mutations were studied in vivo after transformation of SS
      deficient C. reinhardtii T60-3 with mutated genomic DNA. Growth and
      photosynthesis was as in control transformants, except for the slower-growing
      transformants (mutation c) where no mature SS was immuno-detected. However, pSS
      fragments with molecular masses between those of iSS and SS were present even in
      the ribulose-1,5-bisphosphate carboxylase/oxygenase holoenzyme.

PMID- 12049613
TI  - Pathobiology and experimental therapeutics in hepatocellular cholestasis: lessons
      from the hepatocyte couplet model.
AB  - Preparations of isolated liver cells, either freshly prepared or in culture, have
      been available for many years; however, because they lack the polarization of the
      cell in the tissue, their application to the study of processes involved in bile
      formation has been very limited. The hepatocyte couplet model offers a unique
      opportunity to study in vitro the intracellular processes involved: not only the
      physiology and pathophysiology of bile formation, but also the corresponding
      structural and molecular disturbances underlying different experimental models of
      cholestasis. In this review we describe the experimental data generated from this
      model in our laboratory over a period of years, including application of
      hepatocyte couplets to the study of cytoskeletal changes within the hepatocyte
      and mechanisms of hepatoprotection in experimentally induced, clinically relevant
      models of intrahepatic cholestasis.

PMID- 12049612
TI  - Ligatoxin B, a new cytotoxic protein with a novel helix-turn-helix DNA-binding
      domain from the mistletoe Phoradendron liga.
AB  - A new basic protein, designated ligatoxin B, containing 46 amino acid residues
      has been isolated from the mistletoe Phoradendron liga (Gill.) Eichl.
      (Viscaceae). The protein's primary structure, determined unambiguously using a
      combination of automated Edman degradation, trypsin enzymic digestion, and tandem
      MS analysis, was 1-KSCCPSTTAR-NIYNTCRLTG-ASRSVCASLS-GCKIISGSTC-DSGWNH-46.
      Ligatoxin B exhibited in vitro cytotoxic activities on the human lymphoma cell
      line U-937-GTB and the primary multidrug-resistant renal adenocarcinoma cell line
      ACHN, with IC50 values of 1.8 microM and 3.2 microM respectively. Sequence
      alignment with other thionins identified a new member of the class 3 thionins,
      ligatoxin B, which is similar to the earlier described ligatoxin A. As predicted
      by the method of homology modelling, ligatoxin B shares a three-dimensional
      structure with the viscotoxins and purothionins and so may have the same mode of
      cytotoxic action. The novel similarities observed by structural comparison of the
      helix-turn-helix (HTH) motifs of the thionins, including ligatoxin B, and the HTH
      DNA-binding proteins, led us to propose the working hypothesis that thionins
      represent a new group of DNA-binding proteins. This working hypothesis could be
      useful in further dissecting the molecular mechanisms of thionin cytotoxicity and
      of thionin opposition to multidrug resistance, and useful in clarifying the
      physiological function of thionins in plants.

PMID- 12049614
TI  - Asynchronous impairment of calcium homoeostasis in different acinar cells after
      pancreatic duct obstruction in rat.
AB  - Current evidence suggests that alterations within acinar cells are responsible
      for the development of acute pancreatitis. After inducing acute pancreatitis in
      rats by pancreatic duct obstruction, we analysed, using flow cytometry, the
      progressive changes in cytosolic Ca2+ concentrations in individual acinar cells
      from the earliest stages to 48 h after obstruction to investigate whether
      parallel alterations in the homoeostasis of Ca2+ could be defined in the
      different acinar cells throughout the evolution of pancreatitis. Morphological
      alterations of the pancreas, related to the severity of the disease at different
      stages, were observed by electron microscopy. Hyperamylasaemia and progressively
      more severe alterations, such as vacuolization, dilatation of endoplasmic
      reticulum, accumulation of zymogen granules and reorientation towards basolateral
      membrane, were observed during the first 12 h after pancreatic obstruction. A
      significant increase in cytosolic Ca2+ concentration was measured at these stages
      in a particular type of acinar cells (R1) differentiated by flow cytometry with
      low forward scatter (FSC), whereas another representative group of cells (R2)
      with higher FSC values were able to maintain resting cytosolic Ca2+
      concentrations up to 24 h after obstruction. Longer periods of pancreatic duct
      obstruction induced disturbances in Ca2+ homoeostasis in all acinar cells. A
      similar increase in cytosolic Ca2+ load was reached in both R1 and R2 cells when
      acute pancreatitis was completely developed. In conclusion, the homoeostasis of
      Ca2+ in acinar cells is asynchronously impaired during the development of acute
      pancreatitis; cells with higher FSC (R2) appear to be more resistant than R1
      cells.

PMID- 12049615
TI  - Impaired cardiovascular responses to baroreflex stimulation in open-angle and
      normal-pressure glaucoma.
AB  - Autonomic neuropathy may contribute to the pathophysiology of both open-angle and
      normal-pressure glaucoma. However, autonomic function has not been studied
      extensively in these diseases. We evaluated baroreflex control of the heart and
      blood vessels in open-angle and normal-pressure glaucoma. We studied 14 patients
      with open-angle glaucoma, 15 with normal-pressure glaucoma and 17 controls.
      Sinusoidal neck suction (0 to -30 mmHg) was applied at 0.1 Hz to assess the
      sympathetic modulation of the heart and blood vessels, and at 0.2 Hz to assess
      the effect of parasympathetic stimulation on the heart. Baseline recordings
      showed no significant differences between the groups. The RR-interval response of
      the controls to neck suction at 0.1 Hz (3.88+/-0.32 to 6.65+/-0.44 lnms2) was
      significantly greater than that of the open-angle glaucoma patients (4.22+/-0.28
      to 5.56+/-0.26 lnms2) and the normal-pressure glaucoma patients (4.53+/-0.27 to
      5.53+/-0.37 lnms2) (P<0.05). The low-frequency power of diastolic blood pressure
      increased significantly in the controls (0.48+/-0.08 to 2.76+/-0.72 mmHg2;
      P<0.01) during 0.1 Hz neck suction, but did not change significantly in patients
      with either open-angle glaucoma or normal-pressure glaucoma. The RR-interval
      response in the control group (3.45+/-0.52 lnms2) to neck suction at 0.2 Hz was
      significantly greater than that of the normal-pressure glaucoma patients (1.84+/
      0.32 lnms(2)) and the open-angle glaucoma patients (1.58+/-0.35 lnms2) (P<0.05).
      The decreased sympathetic and parasympathetic modulation during baroreceptor
      stimulation in patients with open-angle glaucoma and normal-pressure glaucoma
      suggests that autonomic dysfunction may contribute to the pathogenesis of both
      diseases.

PMID- 12049617
TI  - Does the menstrual cycle influence the sensitivity of vagally mediated
      baroreflexes?
AB  - The menstrual cycle provokes several physiological changes that could influence
      autonomic regulatory mechanisms. We studied the carotid-cardiac baroreflex in ten
      healthy young women on four occasions over the course of their menstrual cycles
      (days 0-8, 9-14, 15-20 and 21-25). We drew blood during each session for analysis
      of oestrogen, progesterone and noradrenaline (norepinephrine) levels, and
      assessed carotid-cardiac baroreflex function by analysing R-R interval responses
      to graded neck pressure sequences. Oestrogen levels followed a classical two-peak
      (cubic) response, with elevated levels on days 9-14 and 21-25 compared with days
      0-8 and 15-20 (P=0.0032), while progesterone levels increased exponentially from
      days 9-14 to days 21-25 (P=0.0063). Noradrenaline levels increased from an
      average of 137 pg/ml during the first three measurement periods to 199 pg/ml
      during days 21-25 (P=0.0456). Carotid-cardiac baroreflex gain and operational
      point were not statistically different at any of the time points during the
      menstrual cycle (P> or =0.18). These findings are consistent with the notion that
      beat-to-beat vagal-cardiac regulation does not change over the course of the
      normal menstrual cycle.

PMID- 12049616
TI  - Homocysteine, folate, methylene tetrahydrofolate reductase genotype and vascular
      morbidity in diabetic subjects.
AB  - In the present study, the determinants of fasting plasma homocysteine in diabetic
      subjects were examined; whether plasma homocysteine and vascular disease are
      related and the influence of the C677T polymorphism in the
      methylenetetrahydrofolate reductase (MTHFR) gene on serum and erythrocyte folate,
      plasma homocysteine and vascular disease. Diabetic clinic subjects (Type I,
      n=354; Type II, n=392) were recalled for a cross-sectional survey. Standard
      methods were used to measure biochemical variables and to characterize vascular
      disease and MTHFR genotype. Plasma homocysteine was significantly and directly
      related to age, male sex and serum urea, and inversely related to serum folate
      and vitamin B12, independently in stepwise regression. When corrected for age and
      sex, homocysteine was significantly related to hard end points of coronary artery
      disease and stroke (each P<0.01), remaining significant when additionally
      adjusted for serum folate (P=0.043 and P=0.019 respectively). Serum folate was
      not clearly related to these events, although there was a trend to associate with
      the lower quintile of serum folate. The MTHFR genotype was not a determinant of
      plasma homocysteine, even in those in the lowest quintile of serum folate, nor of
      vascular disease. TT homozygosity at residue 677 was associated with elevation of
      total erythrocyte folate compared with both other genotypes (P<0.0001), almost
      certainly due to the diversion of 5,10-methylenetetrahydrofolate into derivates
      subsequent to the partial metabolic block that results from the MTHFR enzyme
      defect. In conclusion, in this clinic cohort of people with diabetes, vascular
      disease is related to plasma homocysteine, which is correlated with serum folate.
      The MTHFR genotype does not significantly influence either plasma homocysteine or
      vascular disease, despite it being a determinant of erythrocyte folate, which
      reflects its effect on folate metabolism.

PMID- 12049618
TI  - Increased cationic amino acid flux through a newly expressed transporter in cells
      overproducing nitric oxide from patients with septic shock.
AB  - Increased production of nitric oxide (NO) is thought to be a factor in the
      pathogenesis of many human diseases - among them the hypotension that often
      accompanies sepsis. The supply of the cationic amino acid arginine is known to be
      rate-limiting for NO production. We hypothesized that cationic amino acid
      transport might be increased in cells producing excess NO from patients with
      septic shock. Peripheral blood mononuclear cells were isolated from patients with
      sepsis and from healthy control subjects. The rates of both NO production and
      cationic amino acid uptake were increased in cells from patients with septic
      shock. The increased transport was due almost entirely to an increase in the
      activity of one transporter, subtype y+. The activity of the other major cationic
      amino acid transporter (y+L) was unchanged. The expression of CAT2 mRNA, which
      encodes a y+ transporter protein, was also increased in these cells. We suggest
      that CAT2 might be a therapeutic target to prevent excess NO production in sepsis
      and possibly other human disease states, while leaving basal production
      unchanged.

PMID- 12049619
TI  - Nitric oxide and cationic amino acid transport in sepsis.

PMID- 12049620
TI  - Combined angiotensin-converting enzyme inhibition and adrenomedullin in an ovine
      model of heart failure.
AB  - Advances in the treatment of heart failure may require manipulation of
      neurohumoral responses to cardiac impairment in addition to the established
      strategy of angiotensin-converting enzyme (ACE) inhibition. Importantly, since
      new treatments are likely to be used in conjunction with ACE inhibition therapy,
      the effects of the combination of agents need to be assessed. Adrenomedullin
      (ADM) is a peptide with potent vasodilator and natriuretic actions. ADM and an
      ACE inhibitor (captopril) were administered for 3 h both separately and together
      in eight sheep with heart failure. Both ADM and captopril alone reduced arterial
      pressure, left atrial pressure (greater with captopril) and peripheral
      resistance, and increased cardiac output (greater with ADM). Compared with either
      treatment separately, combined ADM+captopril produced directionally similar but
      significantly greater changes in all haemodynamic variables (particularly falls
      in blood pressure). ADM increased renal sodium and creatinine excretion and
      creatinine clearance, and maintained urine output. Captopril and ADM+captopril
      reduced creatinine excretion and creatinine clearance, while urine volume and
      sodium excretion were not significantly altered. Plasma renin activity rose with
      all active treatments, whereas angiotensin II levels rose during ADM, but fell
      during captopril and ADM+captopril. Aldosterone was reduced by all active
      treatments. ADM+captopril reduced plasma noradrenaline (norepinephrine). In
      conclusion, short-term co-treatment with ADM and an ACE inhibitor produced
      significantly greater decreases in ventricular filling pressures and cardiac
      afterload, and increases in cardiac output, compared with either treatment alone.
      Despite the greater falls in blood pressure (and presumably renal perfusion
      pressure), renal function was maintained at a level similar to that observed with
      captopril alone.

PMID- 12049621
TI  - Action of the endothelin receptor (ETA) antagonist BQ-123 on forearm blood flow
      in young normotensive subjects.
AB  - Endothelin-1 (ET-1) has been proposed to contribute to the regulation of vascular
      tone in humans. BQ-123, an ET(A) receptor antagonist, has also been reported to
      increase forearm blood flow (FBF) in vivo; however, the efficacy of BQ-123 as an
      antagonist of ET-1 has not been evaluated in the forearm. The present study
      investigated the effects of BQ-123 on changes in FBF in response to ET-1 and
      noradrenaline (NA; norepinephrine), taking into account the possible influence of
      vasodilator effects of BQ-123 on responses to vasoconstrictors. Six subjects (age
      25-34 years) participated in a double-blind randomized study. FBF was measured by
      forearm occlusion plethysmography. Drugs were infused intra-arterially into the
      non-dominant arm (study arm) on four separate occasions; the non-infused arm was
      used as a control. The effects of BQ-123 (50 nmol/min for 60 min, or 300 nmol/min
      for 5 min followed by saline for 55 min) were compared with the effects of
      infusion of sodium nitroprusside (SNP; 12 nmol/min for 60 min) or saline on
      vasoconstriction induced by ET-1 (10 pmol/min for 7 min) and NA (120 pmol/min for
      7 min). Infusion of BQ-123 at either dose did not significantly increase FBF,
      whereas SNP increased FBF by 134% (P=0.03). ET-1 significantly reduced FBF, and
      this effect was almost completely inhibited by both doses of BQ-123, but was
      unaffected by SNP. NA also reduced FBF, and this action was unaffected by BQ-123
      or SNP. The data show that BQ-123 is a selective ET-1 antagonist, but do not
      confirm a major role for ET-1 in influencing resting forearm vascular tone in
      young normotensive subjects.

PMID- 12049622
TI  - Endothelin antagonism: physiology or pharmacology?

PMID- 12049623
TI  - Molecular forms of adrenomedullin in pericardial fluid and plasma in patients
      with ischaemic heart disease.
AB  - Experimental studies have demonstrated that adrenomedullin (AM) has a positive
      inotropic action and exerts inhibitory effects against ventricular remodelling as
      an autocrine and paracrine factor. However, there is no clinical evidence for AM
      acting as a local regulator in the human heart. We measured the levels of various
      molecular forms of AM, i.e. an active form of mature AM (AM-m), an intermediate
      inactive form of glycine-extended AM (AM-Gly) and total AM (AM-T=AM-m+AM-Gly), in
      plasma and pericardial fluid using our newly developed immunoradiometric assay in
      consecutive 67 patients undergoing coronary artery bypass graft surgery.
      Pericardial fluid and plasma cAMP, atrial natriuretic peptide and brain
      natriuretic peptide levels were also measured. The relationships between
      pericardial fluid AM levels and ventricular functions and other hormone levels
      were analysed. The level of each molecular form of AM in pericardial fluid was
      closely correlated with that of the other molecular forms of AM in the fluid.
      However, levels were not correlated with those in plasma. AM-T levels were
      slightly higher in pericardial fluid than in plasma (+72%; P<0.05), whereas AM-m
      levels and AM-m/AM-T ratios were markedly higher in pericardial fluid than in
      plasma (AM-m, +994%; AM-m/AM-T ratio, +443%; both P<0.01). AM-m, AM-Gly and AM-T
      levels in pericardial fluid were correlated with indices of left ventricular
      function, and with atrial natriuretic peptide and brain natriuretic peptide
      levels. Interestingly, AM and cAMP levels were positively correlated in plasma,
      but negatively correlated in pericardial fluid. In addition, AM-m, AM-Gly and AM
      T levels in pericardial fluid were higher in patients with acute coronary
      syndrome than in those with stable ischaemic heart disease (AM-m, +80%; AM-Gly,
      +96%; AM-T, +83%; all P<0.01). These results suggest that AM in pericardial fluid
      reflects cardiac synthesis, and that enhanced cardiac secretion of AM is
      associated with left ventricular dysfunction, ventricular overload and myocardial
      ischaemia. Considering that AM has positive inotropic, coronary vasodilatory and
      anti-remodelling actions, increased cardiac AM may play a compensatory role in
      the ischaemic and failing myocardium.

PMID- 12049626
TI  - Calcium-binding parameter of Bacillus amyloliquefaciens alpha-amylase determined
      by inactivation kinetics.
AB  - The irreversible thermal inactivation and the thermodynamics of calcium ion
      binding of Bacillus amyloliquefaciens alpha-amylase in the absence of substrates
      were studied. The enzyme inactivation on heating was apparently followed by first
      order kinetics. The enzyme was stabilized with an increased concentration of
      calcium ion and thus the inactivation was highly dependent on the state of
      calcium binding. The activation parameter for the inactivation suggests an
      unfolding of the enzyme protein upon heating. Values of both the activation
      enthalpy and entropy were increased with a higher calcium ion concentration. An
      inactivation kinetic model is based on the assumption of a two-stage unfolding
      transition in which the bivalent ion dissociation occurs in the first step
      followed by the secondary structural unfolding. This simple kinetic model
      provides both a qualitative and quantitative interpretation of calcium ion
      binding to the enzyme and its effect on the inactivation properties. The specific
      approximations of the kinetic model were strictly followed in the analysis to
      calculate the apparent inactivation rate at each calcium ion concentration in
      terms of the calcium-binding parameters. The enthalpy and entropy changes for the
      calcium ion binding were calculated to be -149 kJ/mol and -360 J.mol(-1).K(-1)
      respectively and these values suggest a strong enthalpic affinity for the
      bivalent ion binding to the enzyme protein. The thermodynamical interpretation
      attempts to provide clear relations between the terms of an apparent inactivation
      rate and the calcium binding.

PMID- 12049625
TI  - The structure of procaspase 6 is similar to that of active mature caspase 6.
AB  - To investigate the structural characteristics and activation mechanism of the
      precursor caspase, genes encoding the inactive pro-form and the active mature
      form of caspase 6 were expressed in Escherichia coli and the proteins of both
      forms were purified to homogeneity. The structure of each protein was
      characterized by chemical cross-linking, size-exclusion chromatography, CD and
      fluorescence spectroscopies. The pro-form caspase 6 exhibits a dimeric structure
      and its overall secondary structure was found to be similar to that of the mature
      caspase 6. Upon the maturation of procaspase 6, the maximum fluorescence
      wavelength lambda(max) was red-shifted from 330 to 337 nm and the fluorescence
      intensity of lambda(max) was increased. This fluorescence spectral change
      indicates that the environment of a tryptophan residue in the substrate-binding
      site can be changed to a more polar one when the procaspase 6 is processed. Taken
      together, our results strongly demonstrate that precursor caspase 6 exists as a
      dimer and its overall structure is similar to that of the active caspase 6. Our
      results also suggest that the local conformational change at the substrate
      binding site, with no drastic change in the overall structure, seems to enable
      precursor caspase 6 to become the active mature enzyme.

PMID- 12049628
TI  - HIV-1 Tat-associated RNA polymerase C-terminal domain kinase, CDK2,
      phosphorylates CDK7 and stimulates Tat-mediated transcription.
AB  - HIV-1 gene expression is regulated by a viral transactivator protein (Tat) which
      induces transcriptional elongation of HIV-1 long tandem repeat (LTR). This
      induction requires hyperphosphorylation of the C-terminal domain (CTD) repeats of
      RNA polymerase II (Pol II). To achieve CTD hyperphosphorylation, Tat stimulates
      CTD kinases associated with general transcription factors of the promoter
      complex, specifically TFIIH-associated CDK7 and positive transcription factor b
      associated CDK9 (cyclin-dependent kinase 9). Other studies indicate that Tat may
      bind an additional CTD kinase that regulates the target-specific phosphorylation
      of RNA Pol II CTD. We previously reported that Tat-associated T-cell-derived
      kinase (TTK), purified from human primary T-cells, stimulates Tat-dependent
      transcription of HIV-1 LTR in vivo [Nekhai, Shukla, Fernandez, Kumar and Lamb
      (2000) Virology 266, 246-256]. In the work presented here, we characterized the
      components of TTK by biochemical fractionation and the function of TTK in
      transcription assays in vitro. TTK uniquely co-purified with CDK2 and not with
      either CDK9 or CDK7. Tat induced the TTK-associated CDK2 kinase to phosphorylate
      CTD, specifically at Ser-2 residues. The TTK fraction restored Tat-mediated
      transcription activation of HIV-1 LTR in a HeLa nuclear extract immunodepleted of
      CDK9, but not in the HeLa nuclear extract double-depleted of CDK9 and CDK7.
      Direct microinjection of the TTK fraction augmented Tat transactivation of HIV-1
      LTR in human primary HS68 fibroblasts. The results argue that TTK-associated CDK2
      may function to maintain target-specific phosphorylation of RNA Pol II that is
      essential for Tat transactivation of HIV-1 promoter. They are also consistent
      with the observed cell-cycle-specific induction of viral gene transactivation.

PMID- 12049627
TI  - Specific detection of the endogenous transient receptor potential (TRP)-1 protein
      in liver and airway smooth muscle cells using immunoprecipitation and Western
      blot analysis.
AB  - Although there are numerous reports of the presence of mRNA encoding the
      transient receptor potential (TRP)-1 protein in animal cells and of the detection
      of the heterologously expressed TRP-1 protein by Western-blot analysis, it has
      proved difficult to unequivocally detect endogenous TRP-1 proteins. A combination
      of immunoprecipitation and Western-blot techniques, employing a polyclonal
      antibody and a monoclonal antibody respectively, was developed. Using this
      technique, a band of approx. 80 kDa was detected in extracts of H4-IIE rat liver
      hepatoma cell line and guinea-pig airway smooth muscle (ASM) cells transfected
      with human TRPC-1 cDNA. In extracts of untransfected H4-IIE cells, ASM cells, rat
      brain and guinea-pig brain, a band of approx. 92 kDa was detected. Reverse
      transcriptase PCR experiments detected cDNA encoding both the alpha- and beta
      isoforms of TRP-1 in H4-IIE cells. Treatment of protein extracts with peptide N
      glycosidase F indicated that the 92 kDa band represents an N-glycosylated
      protein. Western blots conducted with a commercial polyclonal anti-(TRP-1)
      antibody (Alm) detected a band of 120 kDa in extracts of H4-IIE cells and guinea
      pig ASM cells. A combination of immunoprecipitation and Western-blotting
      techniques with the Alm antibody did not detect any bands at 92 kDa or 120 kDa in
      extracts of H4-IIE and ASM cells. It is concluded that (a) the 92-kDa band
      detected in untransfected H4-IIE and ASM cells corresponds to the N-glycosylated
      beta-isoform of endogenous TRP-1, (b) the combined immunoprecipitation and
      Western-blot approach, employing two different antibodies, provides a reliable
      and specific procedure for detecting endogenous TRP-1 proteins, and (c) that
      caution is required in developing and utilizing anti-(TRP-1) antibodies.

PMID- 12049629
TI  - Expression of human electron transfer flavoprotein-ubiquinone oxidoreductase from
      a baculovirus vector: kinetic and spectral characterization of the human protein.
AB  - Electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) is an iron
      sulphur flavoprotein and a component of an electron-transfer system that links 10
      different mitochondrial flavoprotein dehydrogenases to the mitochondrial bc1
      complex via electron transfer flavoprotein (ETF) and ubiquinone. ETF-QO is an
      integral membrane protein, and the primary sequences of human and porcine ETF-QO
      were deduced from the sequences of the cloned cDNAs. We have expressed human ETF
      QO in Sf9 insect cells using a baculovirus vector. The cDNA encoding the entire
      protein, including the mitochondrial targeting sequence, was present in the
      vector. We isolated a membrane-bound form of the enzyme that has a molecular mass
      identical with that of the mature porcine protein as determined by SDS/PAGE and
      has an N-terminal sequence that is identical with that predicted for the mature
      holoenzyme. These data suggest that the heterologously expressed ETF-QO is
      targeted to mitochondria and processed to the mature, catalytically active form.
      The detergent-solubilized protein was purified by ion-exchange and hydroxyapatite
      chromatography. Absorption and EPR spectroscopy and redox titrations are
      consistent with the presence of flavin and iron-sulphur centres that are very
      similar to those in the equivalent porcine and bovine proteins. Additionally, the
      redox potentials of the two prosthetic groups appear similar to those of the
      other eukaryotic ETF-QO proteins. The steady-state kinetic constants of human ETF
      QO were determined with ubiquinone homologues, a ubiquinone analogue, and with
      human wild-type ETF and a Paracoccus-human chimaeric ETF as varied substrates.
      The results demonstrate that this expression system provides sufficient amounts
      of human ETF-QO to enable crystallization and mechanistic investigations of the
      iron-sulphur flavoprotein.

PMID- 12049630
TI  - Human tastin, a proline-rich cytoplasmic protein, associates with the
      microtubular cytoskeleton.
AB  - Tastin was originally identified as an accessory protein for trophinin, a cell
      adhesion molecule that potentially mediates the initial attachment of the human
      embryo to the uterine epithelium. However, no information regarding tastin's
      function is available to date. The present study is aimed at understanding the
      role of tastin in mammalian cells. Hence, we examined the intracellular
      localization of tastin in human cell lines transfected with an expression vector
      encoding influenza virus haemagglutinin (HA)-tagged tastin. Ectopically expressed
      HA-tastin was seen as a pattern resembling the fibres that overlap the
      microtubular cytoskeleton. When HA-tastin-expressing cells were cultured with
      nocodazole to disrupt microtubule (MT) polymerization, tastin was dispersed to
      the entire cytoplasm and an MT sedimentation assay showed tastin in the
      supernatant; however, tastin was sedimented with polymeric MTs in cell lysates
      not treated with nocodazole. Sedimentation assays using HA-tastin mutants deleted
      at the N- or C-terminus revealed MT-binding activity associated with the N
      terminal basic region of tastin. A yeast two-hybrid screen for tastin-interacting
      proteins identified Tctex-1, one of the light chains of cytoplasmic dynein, as a
      tastin-binding protein. Immunoprecipitation and Western-blot analysis confirmed
      binding of HA-tagged tastin and FLAG (Asp-Tyr-Lys-Asp-Asp-Asp-Asp-Lys epitope)
      tagged Tctex-1 in human cells. Furthermore, in vitro assays have demonstrated the
      binding between a fusion protein, glutathione S-transferase-Tctex-1, and in vitro
      translated (35)S-labelled tastin. As Tctex-1 is a component of a MT-based
      molecular motor, these results suggest that tastin plays an important role in
      mammalian cells by associating with the microtubular cytoskeleton.

PMID- 12049631
TI  - Characterization of recombinant glutathionylspermidine synthetase/amidase from
      Crithidia fasciculata.
AB  - Trypanothione [N1,N8-bis(glutathionyl)spermidine] is a unique metabolite found
      only in trypanosomatids, where it subsumes many of the functions of GSH in other
      organisms. In Crithidia fasciculata, two distinct ATP-dependent ligases,
      glutathionylspermidine synthetase (GspS; EC 6.3.1.8) and trypanothione synthetase
      (TryS; EC 6.3.1.9), are involved in the synthesis of trypanothione from GSH and
      spermidine. Both enzymes have been cloned previously, but expression in
      Escherichia coli produced insoluble and inactive protein. Here we report on the
      successful expression of soluble (His)6-tagged C. fasciculata GspS in E. coli.
      Following purification using nickel-chelating affinity chromatography, the tag
      sequence was removed and the enzyme purified to homogeneity by anion-exchange
      chromatography. The kinetic parameters of the recombinant enzyme have been
      determined using a coupled enzyme assay and also by HPLC analysis of end-product
      formation. Under optimal conditions (0.1 M K+-Hepes, pH 7.3) GspS has synthetase
      activity with apparent K(m) values for GSH, spermidine and MgATP of 242, 59 and
      114 microM respectively, and a k(cat) of 15.5 s(-1). Glutathionylspermidine is
      formed as end product and the enzyme lacks TryS activity. Like E. coli GspS, the
      recombinant enzyme also possesses amidase activity (EC 3.5.1.78), hydrolysing
      glutathionylspermidine to GSH and spermidine with a k(cat) of 0.38 s(-1) and a
      K(m) of 500 microM. GspS can also hydrolyse trypanothione at about 1.5% of the
      rate with glutathionylspermidine. A single amino acid mutation (Cys-79-->Ala) is
      shown to ablate the amidase activity without affecting the synthetase activity.

PMID- 12049632
TI  - Evaluation of the role of peroxisome-proliferator-activated receptor alpha in the
      regulation of cardiac pyruvate dehydrogenase kinase 4 protein expression in
      response to starvation, high-fat feeding and hyperthyroidism.
AB  - Inactivation of cardiac pyruvate dehydrogenase complex (PDC) after prolonged
      starvation and in response to hyperthyroidism is associated with enhanced protein
      expression of pyruvate dehydrogenase kinase (PDK) isoform 4. The present study
      examined the potential role of peroxisome-proliferator-activated receptor alpha
      (PPARalpha) in adaptive modification of cardiac PDK4 protein expression after
      starvation and in hyperthyroidism. PDK4 protein expression was analysed by
      immunoblotting in homogenates of hearts from fed or 48 h-starved rats, rats
      rendered hyperthyroid by subcutaneous injection of tri-iodothyronine and a
      subgroup of euthyroid rats maintained on a high-fat/low-carbohydrate diet, with
      or without treatment with the PPARalpha agonist WY14,643. In addition, PDK4
      protein expression was analysed in hearts from fed, 24 h-starved or 6 h-refed
      wild-type or PPARalpha-null mice. PPARalpha activation by WY14,643 in vivo over
      the timescale of the response to starvation failed to up-regulate cardiac PDK4
      protein expression in rats maintained on standard diet (WY14,643, 1.1-fold
      increase; starvation, 1.8-fold increase) or influence the cardiac PDK4 response
      to starvation. By contrast, PPARalpha activation by WY14,643 in vivo
      significantly enhanced cardiac PDK4 protein expression in rats maintained on a
      high-fat diet, which itself increased cardiac PDK4 protein expression. PPARalpha
      deficiency did not abolish up-regulation of cardiac PDK4 protein expression in
      response to starvation (2.9-fold increases in both wild-type and PPARalpha-null
      mice). Starvation and hyperthyroidism exerted additive effects on cardiac PDK4
      protein expression, but PPARalpha activation by WY14,643 did not influence the
      response of cardiac PDK4 protein expression to hyperthyroidism in either the fed
      or starved state. Our data support the hypothesis that cardiac PDK4 protein
      expression is regulated, at least in part, by a fatty acid-dependent, PPARalpha
      independent mechanism and strongly implicate a fall in insulin in either
      initiating or facilitating the response of cardiac PDK4 protein expression to
      starvation.

PMID- 12049633
TI  - Roles of various phospholipases A2 in providing lysophospholipid acceptors for
      fatty acid phospholipid incorporation and remodelling.
AB  - In the present study the lysophospholipid sources for arachidonic (AA) and
      eicosapentaenoic acid (EPA) incorporation into and redistribution within the
      phospholipids of phorbol-ester-differentiated U937 cells was investigated.
      Initially, AA incorporated primarily into choline glycerophospholipids (PC),
      whereas EPA incorporated mainly into ethanolamine glycerophospholipids (PE).
      Bromoenol lactone (BEL), an inhibitor of the Group VI Ca2+-independent
      phospholipase A2 (iPLA2), diminished both lysophosphatidylcholine levels and the
      incorporation of AA into phospholipids. However BEL had little effect on EPA
      incorporation. In concanavalin A-activated cells, EPA, but not AA, incorporation
      was also affected by methyl arachidonyl fluorophosphonate (MAFP), suggesting an
      additional role for the group IV cytosolic phospholipase A2. In the activated
      cells AA and EPA did not compete with each other for incorporation, indicating
      that the pathways for AA and EPA incorporation are partially different. The AA
      and EPA initially incorporated into PC slowly moved to PE in a process that took
      several hours. The transfer of AA and EPA from PC to PE was not inhibited by BEL,
      MAFP or LY311727 [3-(3-acetamide 1-benzyl-2-ethylindolyl-5-oxy)propanesulphonic
      acid], raising the possibility that an as-yet-undetermined phospholipase A2 may
      be involved in fatty acid phospholipid remodelling. A strong candidate to be
      involved in these reactions is a novel Ca2+-independent phospholipase A2 that,
      unlike all known iPLA2s, is resistant to inhibition by BEL and also to MAFP and
      LY311727. The enzyme activity cleaves both PC and PE and is thus able to provide
      the lysoPC and lysoPE acceptors required for the fatty acid acylation reactions.

PMID- 12049634
TI  - Membrane-associated dipeptidyl peptidase IV is involved in encystation-specific
      gene expression during Giardia differentiation.
AB  - Giardia is a flagellated protozoan that resides in the upper small intestine of
      its vertebrate host and is the most common cause of defined waterborne diarrhoea
      worldwide. Giardia trophozoites undergo significant biological changes to survive
      outside the host by differentiating into infective cysts. Encystation is thus
      essential for transmission of the parasite among susceptible hosts. In the
      present study, we report that bestatin, a competitive inhibitor of
      aminopeptidases, blocks cyst formation in vitro by abolishing the expression of
      encystation-specific genes, such as those coding for cyst wall proteins. Bestatin
      does not affect proliferating trophozoites, indicating that its effect is
      encystation-specific. Using biochemical and molecular biological approaches, we
      identified the enzyme inhibited by bestatin and cloned its corresponding gene.
      Sequence similarity indicated that this enzyme belongs to a family of dipeptidyl
      peptidases. Our results suggest that a specific proteolytic event caused by a
      constitutively expressed membrane-associated dipeptidyl peptidase IV is necessary
      for encystation of Giardia.

PMID- 12049635
TI  - Effects of modifications of alpha-crystallin on its chaperone and other
      properties.
AB  - The role of alpha-crystallin, a small heat-shock protein and chaperone, may
      explain how the lens stays transparent for so long. alpha-Crystallin prevents the
      aggregation of other lens crystallins and proteins that have become unfolded by
      'trapping' the protein in a high-molecular-mass complex. However, during aging,
      the chaperone function of alpha-crystallin becomes compromised, allowing the
      formation of light-scattering aggregates that can proceed to form cataracts.
      Within the central part of the lens there is no turnover of damaged protein, and
      therefore post-translational modifications of alpha-crystallin accumulate that
      can reduce chaperone function; this is compounded in cataract lenses. Extensive
      in vitro glycation, carbamylation and oxidation all decrease chaperone ability.
      In the present study, we report the effect of the modifiers malondialdehyde,
      acetaldehyde and methylglyoxal, all of which are pertinent to cataract. Also
      modification by aspirin, which is known to delay cataract and other diseases, has
      been investigated. Recently, two point mutations of arginine residues were shown
      to cause congenital cataract. 1,2-Cyclohexanedione modifies arginine residues,
      and the extent of modification needed for a change in chaperone function was
      investigated. Only methylglyoxal and extensive modification by 1,2
      cyclohexanedione caused a decrease in chaperone function. This highlights the
      robust nature of alpha-crystallin.

PMID- 12049637
TI  - Solution structure and backbone dynamics of human epidermal-type fatty acid
      binding protein (E-FABP).
AB  - Human epidermal-type fatty acid-binding protein (E-FABP) belongs to a family of
      intracellular 14-15 kDa lipid-binding proteins, whose functions have been
      associated with fatty acid signalling, cell growth, regulation and
      differentiation. As a contribution to understanding the structure-function
      relationship, we report in the present study features of its solution structure
      and backbone dynamics determined by NMR spectroscopy. Applying multi-dimensional
      high-resolution NMR techniques on unlabelled and 15N-enriched recombinant human E
      FABP, the 1H and 15N resonance assignments were completed. On the basis of 2008
      distance restraints, the three-dimensional solution structure of human E-FABP was
      subsequently obtained (backbone atom root-mean-square deviation of 0.92+/-0.11 A;
      where 1 A=0.1 nm), consisting mainly of 10 anti-parallel beta-strands that form a
      beta-barrel structure. 15N relaxation experiments (T1, T2 and heteronuclear
      nuclear Overhauser effects) at 500, 600 and 800 MHz provided information on the
      internal dynamics of the protein backbone. Nearly all non-terminal backbone amide
      groups showed order parameters S(2)>0.8, with an average value of 0.88+/-0.04,
      suggesting a uniformly low backbone mobility in the nanosecond-to-picosecond time
      range. Moreover, hydrogen/deuterium exchange experiments indicated a direct
      correlation between the stability of the hydrogen-bonding network in the beta
      sheet structure and the conformational exchange in the millisecond-to-microsecond
      time range. The features of E-FABP backbone dynamics elaborated in the present
      study differ markedly from those of the phylogenetically closely related heart
      type FABP and the more distantly related ileal lipid-binding protein, implying a
      strong interdependence with the overall protein stability and possibly also with
      the ligand-binding affinity for members of the lipid-binding protein family.

PMID- 12049636
TI  - gamma-Glutamyl transpeptidase expression in Ewing's sarcoma cells: up-regulation
      by interferons.
AB  - The genetic hallmark of Ewing's sarcoma family of tumours (ET) is the presence of
      the translocation t(11;22)(q24;q12), which creates the ET fusion gene, leading to
      cellular transformation. Five human gamma-glutamyl transpeptidase (gamma-GT)
      genes are located near the chromosomal translocation in ET. gamma-GT is a major
      enzyme involved in glutathione homoeostasis. Five human cell lines representative
      of primary or metastatic tumours were investigated to study whether gamma-GT
      alterations could occur at the chromosomal breaks and rearrangements in ET. As
      shown by enzymic assays and FACS analyses, all ET cell lines consistently
      expressed a functional gamma-GT which however did not discriminate steps of ET
      progression. As shown previously [Sanceau, Hiscott, Delattre and Wietzerbin
      (2000) Oncogene 19, 3372-3383], ET cells respond to the antiproliferative effects
      of interferons (IFNs) type I (alpha and beta) and to a much less degree to IFN
      type II (gamma). IFN-alpha and -beta arrested cells in the S-phase of the cell
      cycle. We found an enhancement of gamma-GT mRNA species with IFN-alpha and -beta
      by reverse transcriptase-PCR analyses. This is reflected by up-regulation of
      gamma-GT protein, which coincides with the increase in gamma-GT-specific enzymic
      activity. Similarly, IFNs up-regulate the levels of gamma-GT in another IFN
      responsive B cell line. Whether this up-regulation of gamma-GT by IFNs is of
      physiological relevance to cell behaviour remains to be studied.

PMID- 12049639
TI  - Correction of mucopolysaccharidosis type IIIb fibroblasts by lentiviral vector
      mediated gene transfer.
AB  - Mucopolysaccharidosis type IIIB (MPS IIIB; or Sanfilippo syndrome type B) is a
      lysosomal disease, due to glycosaminoglycan storage caused by mutations on the
      alpha-N-acetylglucosaminidase (NAGLU) gene. The disease is characterized by
      neurological dysfunction but relatively mild somatic manifestations. No effective
      treatment is available for affected patients. In the present study, we evaluated
      the role of a lentiviral vector as the transducing agent of NAGLU cDNA in MPS
      IIIB fibroblasts. The vector expressed high transduction efficiency and high
      levels of enzymic activity, 20-fold above normal levels, persisting for at least
      2 months. PCR experiments confirmed the integration of the viral vector into the
      target genome. The NAGLU activity restored by virus infection was sufficient to
      normalize glycosaminoglycan accumulation, which is directly responsible for the
      disease phenotype. Metabolic labelling experiments on transduced fibroblasts
      exhibited, in the medium and in cellular lysates, polypeptide forms of 84 and 80
      kDa respectively related to the precursor and mature forms of the enzyme. The
      enzyme secreted by transduced MPS IIIB fibroblasts was endocytosed in deficient
      cells by the mannose 6-phosphate system. Thus we show that lentiviral vectors may
      provide a therapeutic approach for the treatment of MPS IIIB disease.

PMID- 12049638
TI  - Involvement of matrix metalloproteinases in the adipose conversion of 3T3-L1
      preadipocytes.
AB  - When mouse 3T3-L1 preadipocytes are induced to differentiate into adipocytes,
      they change from an extended fibroblast-like morphology to a rounded one. This
      change most likely occurs through extracellular matrix remodelling, a process
      known to be mediated in part by matrix metalloproteinases (MMPs). In this study,
      we have shown by semi-quantitative reverse transcriptase-PCR, zymographic and
      immunoblot analysis that MMP-2, MMP-9 and membrane type 1 (MT1)-MMP are regulated
      during adipose conversion. To assess the importance of MMPs for adipocytic
      differentiation we have used MMP-specific inhibitors as well as neutralizing
      antibodies. Treatment of 3T3-L1 preadipocytes with the broad MMP inhibitor
      Ilomastat or the more restricted MMP-2 Inhibitor I prevented their
      differentiation into adipocytes in a dose-dependent manner, as evidenced by
      absence of triglyceride accumulation. Inhibitor treatment prevented the
      fibronectin-network degradation, as well as the induction of the genes for
      peroxisome-proliferator-activated receptor gamma and adipsin, two adipocyte
      phenotype markers. Inhibitor treatment was effective when applied during the
      early stages of adipocytic conversion, whereas inhibitor treatment during later
      stages had little effect. Inhibitor treatment did not inhibit clonal mitotic
      expansion; nor did it affect the expression pattern of the adipogenic
      transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta) or its
      nuclear translocation. It did, however, markedly reduce C/EBPbeta DNA-binding
      capacity. Taken together, these results suggest that MMPs, and notably MMP-2 and
      MMP-9, may be necessary mediators of adipocytic differentiation of 3T3-L1 cells.

PMID- 12049641
TI  - Expression of solute carrier 7A4 (SLC7A4) in the plasma membrane is not
      sufficient to mediate amino acid transport activity.
AB  - Member 4 of human solute carrier family 7 (SLC7A4) exhibits significant sequence
      homology with the SLC7 subfamily of human cationic amino acid transporters
      (hCATs) [Sperandeo, Borsani, Incerti, Zollo, Rossi, Zuffardi, Castaldo,
      Taglialatela, Andria and Sebastio (1998) Genomics 49, 230-236]. It is therefore
      often referred to as hCAT-4 even though no convincing transport activity has been
      shown for this protein. We expressed SLC7A4 in Xenopus laevis oocytes, but could
      not detect any transport activity for cationic, neutral or anionic amino acids or
      for the polyamine putrescine. In addition, human glioblastoma cells stably
      overexpressing a fusion protein between SLC7A4 and the enhanced green fluorescent
      protein (EGFP) did not exhibit an increased transport activity for l-arginine.
      The lack of transport activity was not due to a lack of SLC7A4 protein expression
      in the plasma membrane, as in both cell types SLC7A4-EGFP exhibited a similar
      subcellular localization and level of protein expression as functional hCAT-EGFP
      proteins. The expression of SLC7A4 can be induced in NT2 teratocarcinoma cells by
      treatment with retinoic acid. However, also for this endogenously expressed
      SLC7A4, we could not detect any transport activity for l-arginine. Our data
      demonstrate that the expression of SLC7A4 in the plasma membrane is not
      sufficient to induce an amino acid transport activity in X. laevis oocytes or
      human cells. Therefore, SLC7A4 is either not an amino acid transporter or it
      needs additional (protein) factor(s) to be functional.

PMID- 12049640
TI  - Differential role of glycolipid-enriched membrane domains in glycoprotein VI- and
      integrin-mediated phospholipase Cgamma2 regulation in platelets.
AB  - The platelet collagen receptor glycoprotein VI (GPVI) and the fibrinogen receptor
      integrin alphaIIbbeta3 trigger intracellular signalling cascades involving the
      tyrosine kinase Syk, the adapter SLP-76 and phospholipase Cgamma2 (PLCgamma2).
      Similar pathways are activated downstream of immune receptors in lymphocytes,
      where they have been localized in part to glycolipid-enriched membrane domains
      (GEMs). Here we provide several lines of evidence that GPVI-mediated tyrosine
      phosphorylation of PLCgamma2 in platelets is dependent on GEM-organized
      signalling and utilizes the GEM resident adapter protein LAT (linker for
      activation of T cells). In sharp contrast, although fibrinogen binding to
      platelets stimulates alphaIIbbeta3-dependent activation of Syk and tyrosine
      phosphorylation of SLP-76 and PLCgamma2, it does not utilize GEMs to promote
      these responses or to support platelet aggregation. These results establish that
      GPVI and alphaIIbbeta3 trigger distinct patterns of receptor signalling in
      platelets, leading to tyrosine phosphorylation of PLCgamma2, and they highlight
      the role of GEMs in compartmentalizing signalling reactions involved in
      haemostasis.

PMID- 12049642
TI  - Cytoplasmic domains of the reduced folate carrier are essential for trafficking,
      but not function.
AB  - The reduced folate carrier (RFC) protein has a secondary structure consistent
      with the predicted 12 transmembrane (TM) domains, intracellular N- and C-termini
      and a large cytoplasmic loop between TM6 and TM7. In the present study, the role
      of the cytoplasmic domains in substrate transport and protein biogenesis were
      examined using an array of hamster RFC deletion mutants fused to enhanced green
      fluorescent protein and expressed in Chinese hamster ovary cells. The N- and C
      terminal tails were removed both individually and together, or the large
      cytoplasmic loop was modified such that the domain size and role of conserved
      sequences could be examined. The loss of the N- or C-terminal tails did not
      appear to significantly disrupt protein function, although both termini appeared
      to have a role in the efficiency with which molecules exited the endoplasmic
      reticulum to localize at the plasma membrane. There appeared to be both size and
      sequence requirements for the intracellular loop, which are able to drastically
      affect protein stability and function unless met. Furthermore, there might be an
      indirect role for the loop in substrate translocation, since even moderate
      changes significantly reduced the V(max) for methotrexate transport. Although
      these cytoplasmic domains do not appear to be absolutely essential for substrate
      transport, each one is important for biogenesis and localization.

PMID- 12049643
TI  - TcGPXII, a glutathione-dependent Trypanosoma cruzi peroxidase with substrate
      specificity restricted to fatty acid and phospholipid hydroperoxides, is
      localized to the endoplasmic reticulum.
AB  - Until recently, it had been thought that trypanosomes lack glutathione peroxidase
      activity. Here we report the subcellular localization and biochemical properties
      of a second glutathione-dependent peroxidase from Trypanosoma cruzi (TcGPXII).
      TcGPXII is a single-copy gene which encodes a 16 kDa protein that appears to be
      specifically dependent on glutathione as the source of reducing equivalents.
      Recombinant TcGPXII was purified and shown to have peroxidase activity towards a
      narrow substrate range, restricted to hydroperoxides of fatty acids and
      phospholipids. Analysis of the pathway revealed that TcGPXII activity could be
      readily saturated by glutathione and that the peroxidase functioned by a Ping
      Pong mechanism. Enzyme reduction was shown to be the rate-limiting step in this
      pathway. Using immunofluorescence, TcGPXII was shown to co-localize with a
      homologue of immunoglobulin heavy-chain binding protein (BiP), a protein
      restricted to the endoplasmic reticulum and Golgi. As the smooth endoplasmic
      reticulum is the site of phospholipid and fatty acid biosynthesis, this suggests
      that TcGPXII may play a specific role in the T. cruzi oxidative defence system by
      protecting newly synthesized lipids from peroxidation.

PMID- 12049644
TI  - Limnanthes douglasii lysophosphatidic acid acyltransferases: immunological
      quantification, acyl selectivity and functional replacement of the Escherichia
      coli plsC gene.
AB  - Antibodies were raised against the two membrane-bound lysophosphatidic acid
      acyltransferase (LPAAT) enzymes from Limnanthes douglasii (meadowfoam), LAT1 and
      LAT2, using the predicted soluble portion of each protein as recombinant protein
      antigens. The antibodies can distinguish between the two acyltransferase proteins
      and demonstrate that both migrate in an anomalous fashion on SDS/PAGE gels. The
      antibodies were used to determine that LAT1 is present in both leaf and
      developing seeds, whereas LAT2 is only detectable in developing seeds later than
      22 daf (days after flowering). Both proteins were found exclusively in microsomal
      fractions and their amount was determined using the recombinant antigens as
      quantification standards. LAT1 is present at a level of 27 pg/microg of membrane
      protein in leaf tissue and <or=12.5 pg/microg of membrane protein in developing
      embryos. The amount of LAT2 reaches a peak at 305 pg/microg of membrane protein
      25 daf and is not expressed 20 daf or before. This is the first study to quantify
      these membrane-bound proteins in a plant tissue. The maximal level of LAT2
      protein coincides with the maximal level of erucic acid synthesis in the seeds.
      Both full-length proteins were expressed in the Escherichia coli LPAAT mutant
      JC201, and membranes from these strains were used to investigate the substrate
      selectivity of these two enzymes, demonstrating that they are different. Finally,
      we report that LAT2 and a maize LPAAT enzyme (MAT1) can functionally replace the
      E. coli plsC gene after its deletion in the chromosome, whereas LAT1 and a
      coconut LPAAT (Coco1) cannot. This is probably due to differences in substrate
      utilization.

PMID- 12049645
TI  - Multiple forms of the catalytic centre, CuZ, in the enzyme nitrous oxide
      reductase from Paracoccus pantotrophus.
AB  - Nitrous oxide reductase catalyses the reduction of nitrous oxide to dinitrogen at
      a unique tetranuclear copper site, called Cu(Z), which has a central inorganic
      sulphide ligand. Limited incubation with oxygen during the preparation of nitrous
      oxide reductase from Paracoccus pantotrophus results in changed redox properties
      of the catalytic centre by comparison with anaerobic preparations. While the
      anaerobically purified enzyme has a catalytic centre which performs a single
      electron step at a midpoint potential of E(m)=+60 mV versus the standard hydrogen
      electrode (n=1), the altered centre shows no redox change under similar
      experimental conditions. Spectroscopic properties of this 'redox fixed' centre
      are similar to spectra of the reduced 'redox active' form of CuZ, although the
      positions and intensities of a number of transitions are changed in the optical
      spectrum. These observations are interpreted in terms of two forms of the
      catalytic centre, called CuZ and CuZ*. The structural relationship between these
      forms is unclear. EPR and magnetic circular dichroism spectra suggest that the
      basic Cu4S structure is common to both. Curiously, steady-state activity of the
      aerobic enzyme preparation is slightly increased despite the fact the catalytic
      centre does not undergo detectable redox changes.

PMID- 12049646
TI  - Cloning, structural characterization and functional expression of a zebrafish
      bradykinin B2-related receptor.
AB  - The actions of bradykinin (BK) in mammals are mediated through the activation of
      the B1 and B2 BK receptors. The only BK receptor that has been cloned from a non
      mammalian species is a B2-like receptor from the chicken (termed the ornithokinin
      receptor). Pharmacological studies have demonstrated the presence of BK receptors
      in tissues of teleost fishes, such as trout and cod, but the ligand-binding
      properties of these receptors differ appreciably from those of the mammalian and
      chicken receptors. We report here the cloning of a B2-like receptor in zebrafish
      that shares 35% identity with human B2 and 30% identity with human B1.
      Phylogenetic analyses confirm a closer relationship with B2 than B1. The receptor
      gene was mapped to linkage group 17, which is syntenic to the human B2-B1 gene
      region. After functional expression of the zebrafish B2 receptor in mammalian
      cells, nanomolar concentrations of trout BK ([Arg0,Trp5,Leu8]-BK) and the
      derivative [des-Arg0,Trp5,Leu8]-BK (where 'des' indicates a missing amino acid)
      induced a significant transient rise in intracellular free Ca2+. The B1-selective
      analogue [Arg0,Trp5,Leu8,des-Arg9]-BK was inactive at nanomolar concentrations.
      Taken together, these results strongly support the gene's identity as a piscine
      orthologue of the mammalian B2 receptor.

PMID- 12049647
TI  - Identification, cloning and expression of the mouse N-acetylglutamate synthase
      gene.
AB  - In ureotelic animals, N-acetylglutamate (NAG) is an essential allosteric
      activator of carbamylphosphate synthetase I (CPSI), the first enzyme in the urea
      cycle. NAG synthase (NAGS; EC 2.3.1.1) catalyses the formation of NAG from
      glutamate and acetyl-CoA in liver and intestinal mitochondria. This enzyme is
      supposed to regulate ureagenesis by producing variable amounts of NAG, thus
      modulating CPSI activity. Moreover, inherited deficiencies in NAGS have been
      associated with hyperammonaemia, probably due to the loss of CPSI activity.
      Although the existence of the NAGS protein in mammals has been known for decades,
      the gene has remained elusive. We identified the mouse (Mus musculus) and human
      NAGS genes using their similarity to the respective Neurospora crassa gene. NAGS
      was cloned from a mouse liver cDNA library and was found to encode a 2.3 kb
      message, highly expressed in liver and small intestine with lower expression
      levels in kidney, spleen and testis. The deduced amino acid sequence contains a
      putative mitochondrial targeting signal at the N-terminus. The cDNA sequence
      complements an argA (NAGS)-deficient Escherichia coli strain, reversing its
      arginine auxotrophy. His-tagged versions of the pre-protein and two putative
      mature proteins were each overexpressed in E. coli, and purified to apparent
      homogeneity by using a nickel-affinity column. The pre-protein and the two
      putative mature proteins catalysed the NAGS reaction but one of the putative
      mature enzymes had significantly higher activity than the pre-protein. The
      addition of l-arginine increased the catalytic activity of the purified
      recombinant NAGS enzymes by approx. 2-6-fold.

PMID- 12049648
TI  - Disruption of iron-sulphur cluster N2 from NADH: ubiquinone oxidoreductase by
      site-directed mutagenesis.
AB  - We have cloned and inactivated, by repeat-induced point mutations, the nuclear
      gene encoding the 19.3 kDa subunit of complex I (EC 1.6.5.3) from Neurospora
      crassa, the homologue of the bovine PSST polypeptide. Mitochondria from mutant
      nuo19.3 lack the peripheral arm of complex I while its membrane arm accumulates.
      Transformation with wild-type cDNA rescues this phenotype and assembly of complex
      I is restored. To interfere with assembly of a proposed bound iron-sulphur
      cluster, site-directed mutants were constructed by introducing cDNA with altered
      codons for two adjacent cysteines, Cys-101 and Cys-102. The mutant complexes were
      purified and their enzymic activities and EPR and UV/visible spectra were
      analysed. Either of the mutations abolishes assembly of iron-sulphur cluster N2,
      showing that this redox group is bound to the 19.3 kDa protein. We also observed
      an interference with the reduction of redox group X, suggesting that cluster N2
      is the electron donor to this high-potential redox group.

PMID- 12049649
TI  - Mapping of a spectrin-binding domain of human erythrocyte membrane protein 4.2.
AB  - Protein 4.2 is a major component of the red blood cell membrane skeleton.
      Deficiency of protein 4.2 is linked with a variety of hereditary haemolytic
      anaemias. However, the interactions of protein 4.2 with other proteins of the
      erythrocyte membrane remain poorly understood. The major membrane-binding site
      for protein 4.2 resides on the cytoplasmic domain of band 3. Protein 4.2
      interacts directly with spectrin in solution, suggesting that it stabilizes
      interactions between the membrane skeleton and the erythrocyte membrane. A 30 kDa
      polypeptide, with its N-terminus corresponding to amino acid residue 269, derived
      by partial proteolysis of protein 4.2, was found to interact with biotinylated
      spectrin in gel renaturation assays. A series of overlapping glutathione S
      transferase fusion peptides were constructed, and an alpha-helical domain
      encompassing residues 470-492 was found to be instrumental in mediating protein
      4.2-spectrin interactions. Direct binding of a synthetic peptide, with the
      sequence corresponding to residues 470-492, to spectrin and the ability of the
      peptide to inhibit spectrin binding of protein 4.2 confirmed that these residues
      are crucial in mediating protein 4.2-spectrin interactions.

PMID- 12049650
TI  - Hydrolysable ATP is a requirement for the correct interaction of molecular
      chaperonins cpn60 and cpn10.
AB  - Over recent years the binding ability of the molecular chaperone cpn60 (GroEL14)
      and its co-chaperone cpn10 (GroES7) has been reported to occur under an
      assortment of specific conditions from the use of non-hydrolysable ATP analogues
      (namely adenosine 5'-[gamma-thio]triphosphate) to requiring hydrolysable ATP for
      any interaction to occur. We have investigated this further using the molecular
      hydrodynamic methods (hydrodynamic bead modelling, sedimentation-velocity
      analytical ultracentrifugation and dynamic light-scattering), allowing the
      process to be followed under physiologically relevant dilute solution conditions,
      combined with absorption spectrophotometry to determine GroES7-GroEL14
      interaction through the rate inhibition of the cpn60's ATPase activity by GroES7.
      The results found here indicate that the presence of hydrolysable ATP is required
      to facilitate correct GroES7 interaction with GroEL14 in solution.

PMID- 12049651
TI  - Composition of the lambda plasmid heritable replication complex.
AB  - Previous studies indicated during replication of plasmids derived from
      bacteriophage lambda (the so-called lambda plasmids), that, once assembled,
      replication complex can be inherited by one of the two daughter plasmid copies
      after each replication round, and may function in subsequent replication rounds.
      It seems that similar processes occur during replication of other DNA molecules,
      including chromosomes of the yeast Saccharomyces cerevisiae. However, apart from
      some suggestions based on genetic experiments, composition of the lambda
      heritable replication complex remains unknown. In amino acid-starved Escherichia
      coli relA mutants, replication of lambda plasmid DNA is carried out exclusively
      by the heritable replication complex as assembly of new complexes is impaired due
      to inhibition of protein synthesis. Here, using a procedure based on in vivo
      cross-linking, cell lysis, immunoprecipitation with specific sera, de-cross
      linking and PCR analysis, we demonstrate that the lambda heritable replication
      complex consists of O, P, DnaB and, perhaps surprisingly, DnaK proteins.

PMID- 12049652
TI  - Desensitization of endothelial nitric oxide synthase by receptor agonists.
AB  - Stimulation of endothelial cells with receptor agonists leads to an activation of
      endothelial nitric oxide synthase (eNOS) that only lasts for a short duration. A
      more prolonged effect, however, is observed in response to non-receptor agonists,
      such as Ca2+ ionophores or thapsigargin (TG). To investigate the molecular
      mechanisms underlying the rapid deactivation of eNOS after stimulation with
      receptor agonists, we measured the time courses of eNOS activation and
      intracellular free Ca2+ concentration ([Ca2+]i) in response to bradykinin (BK)
      and ATP. Incubation of porcine aortic endothelial cells with BK (1 microM) in the
      presence of 3 mM extracellular Ca2+ increased [Ca2+]i from 110 to 350 nM and
      enhanced the rate of l-[3H]citrulline formation from 0.1 to 5 fmol/min. In the
      absence of extracellular Ca2+, the BK-induced increase in [Ca2+]i was only
      marginal (from 30 to 110 nM) and not sufficient to activate eNOS. When Ca(2+)
      (final concentration 3 mM) was added 10 min after BK, [Ca2+]i increased to 330 nM
      within 3 min, but interestingly, formation of l-[3H]citrulline was not
      detectable. A similar phenomenon was observed with ATP, but not with Ca2+
      ionophores or TG. This indicates that stimulation of endothelial cells with
      receptor agonists leads to desensitization of eNOS, which renders the enzyme
      insensitive to activation by subsequent increases in [Ca2+]i. However, when ATP
      was added to BK-pretreated cells or, conversely, BK to ATP-pretreated cells,
      activation of eNOS was comparable with that of untreated cells, suggesting that
      BK and ATP affect different pools of eNOS. The desensitization of eNOS was
      reversible, since removal of ATP or BK from the incubation buffer restored the
      response to the respective agonist within 20 min. In addition to the transient
      Ca2+ signal, desensitization of eNOS may represent a further mechanism by which
      endothelial cells rapidly terminate receptor-dependent NO formation.

PMID- 12049653
TI  - Role of ATP-binding motifs on DNA-binding activity and biological function of
      Rhp51, a Rad51 homologue in fission yeast.
AB  - Rhp51, a RecA and Rad51 homologue of Schizosaccharomyces pombe, plays a pivotal
      role in homologous recombination and recombinational repair. It has a set of the
      well-conserved type A and type B ATP-binding motifs, which are highly conserved
      in all RecA homologues. In a previous study [Kim, Lee, Park, Park and Park (2001)
      Nucleic Acids Res. 29, 1724-1732], we reported that a single mutation of the
      conserved lysine in A motif [Lys(155)-->Ala (K155A)] destroyed the DNA repair
      ability of Rhp51 and that overexpression of this mutant protein conferred
      dominant negativity. In the present paper, we investigated DNA-binding properties
      of recombinant Rhp51 and its mutant proteins. Purified Rhp51 protein showed ATP
      dependent double- and single-strand DNA-binding activities. To characterize the
      role of ATP-binding motifs, we generated Rhp51 K155A and Rhp51 Asp(244)-->Gln
      (D244Q), which have a single amino acid substitution in A and B motifs
      respectively. Interestingly, K155A and D244Q mutations impaired ATP-dependent DNA
      binding in a different manner. K155A lost the DNA binding itself, whereas D244Q
      maintained the binding ability but lost the ATP dependency. However, despite the
      difference in DNA-binding ability, both mutations failed to rescue the
      methylmethane sulphonate and UV sensitivity of the rhp51Delta mutant. Together,
      these results suggested that not only the DNA binding but also the ATP dependence
      in DNA binding is required for proper in vivo functioning of Rhp51.

PMID- 12049654
TI  - Biphasic regulation of extracellular-signal-regulated protein kinase by leptin in
      macrophages: role in regulating STAT3 Ser727 phosphorylation and DNA binding.
AB  - Activation of the transcription factor signal transducer and activator of
      transcription 3 (STAT3) requires dimerization that is induced by phosphorylation
      of Tyr705, but its activity can be further modulated by phosphorylation at Ser727
      in a manner that is dependent on cell context and the stimulus used. The role of
      STAT3 Ser727 phosphorylation in leptin signalling is currently not known. While
      cells transfected with the signalling-competent long form of the leptin receptor
      (ObRb) have been used to study leptin signalling, these are likely to be of
      limited use in studying STAT3 Ser727 phosphorylation due to the importance of
      cell background in determining the nature of the response. However, we have
      recently found that J774.2 macrophages endogenously express high levels of ObRb,
      and using these cells we find that leptin stimulates STAT3 phosphorylation on
      both Tyr705 and Ser727. The phosphorylation of Ser727 was not affected by
      rapamycin or the protein kinase C inhibitor H7 [1-(5-isoquinolinylsulphonyl)-2
      methylpiperazine dihydrochloride]. While the MEK-1 [mitogen-activated protein
      kinase (MAP kinase)/extracellular-signal-related kinase (ERK) kinase-1] inhibitor
      PD98059 [(2-amino-3'-methoxyphenyl)oxanaphthalen-4-one] had no effect on leptin
      stimulated phosphorylation of STAT3 Tyr705, it greatly attenuated leptin's
      effects on STAT3 Ser727 phosphorylation. Further, Ob's effect on the DNA binding
      activity of STAT3 was also greatly reduced at all time points by PD98059. Leptin
      induced ERK activation in J774.2 cells shows a biphasic pattern, with an initial
      reduction in ERK phosphorylation for up to 10 min following leptin stimulation,
      while at later time points phosphorylation of ERK was increased above basal
      levels. The increase in ERK activity corresponded with an increase in both
      phosphorylation of Ser727 and STAT3 DNA binding activity. These data provide the
      first evidence that ERK-mediated phosphorylation of Ser727 is required for full
      stimulation of STAT3 by leptin.

PMID- 12049657
TI  - Life sentences: elementary zenetics--do or dai.

PMID- 12049656
TI  - Grain of truth.

PMID- 12049655
TI  - Doxorubicin and octreotide induce a 40 kDa breakdown product of p53 in human
      hepatoma and tumoral colon cell lines.
AB  - The chemotherapeutic drug doxorubicin and the anti-proliferative long-acting
      somatostatin analogue octreotide, both used in cancer treatment, have been shown
      to increase the expression of the p53 tumour suppressor protein. In the present
      study, we demonstrate by Western-blot analysis that, in addition to the p53
      protein, these molecules were able to induce the expression of a shorter protein
      with an apparent molecular mass of 40 kDa (p40), recognized by antibodies raised
      against the N-terminus of p53. This induction was present in tumoral and non
      tumoral cells and did not depend on the status of the endogenous p53 protein. The
      p40 protein was significantly induced after 3 h of cell treatment with
      doxorubicin or octreotide, remained stable until 24 h and was located in the
      nuclear extract. Using reverse primers corresponding to each exon of the p53
      gene, only one transcript was amplified by reverse transcriptase-PCR. This
      suggested that p40 was issued from a post-translational modification and not from
      an alternative splicing. This protein was not recognized by the PAb421 antibody,
      suggesting that it was issued from a cleavage of the p53 C-terminal region
      (p40deltaC). Furthermore, this cleavage was not dependent on caspase activity. In
      conclusion, these results support the hypothesis that this post-translational
      modification plays a significant role in the regulation of multiple p53
      signalling pathways. These results also suggest that octreotide, a molecule with
      different signalling pathways, was able as doxorubicin to generate a p53
      breakdown product.

PMID- 12049658
TI  - Microarrays and molecular markers for tumor classification.
AB  - Human cancers have traditionally been classified according to their tissue of
      origin, histological characteristics and, to some extent, molecular markers.
      Clinical studies have associated different tumor classes with differences in
      prognosis and in response to therapy. Measurement of the expression of thousands
      of genes in hundreds of cancer specimens has begun to reveal novel molecularly
      defined subclasses of tumor; some of these classes appear to predict clinical
      behavior, while others may define tumor types that are ripe for directed
      development of therapeutics. Unfortunately, at present, differences between
      studies of similar tumor types can be as striking as their similarities.

PMID- 12049659
TI  - Foliage in Madrid.

PMID- 12049660
TI  - Genome packaging and expression.

PMID- 12049661
TI  - Microarray profile of differentially expressed genes in a monkey model of
      allergic asthma.
AB  - BACKGROUND: Inhalation of Ascaris suum antigen by allergic monkeys causes an
      immediate bronchoconstriction and delayed allergic reaction, including a
      pulmonary inflammatory infiltrate. To identify genes involved in this process,
      the gene-expression pattern of allergic monkey lungs was profiled by microarrays.
      Monkeys were challenged by inhalation of A. suum antigen or given interleukin-4
      (IL-4) treatment; lung tissue was collected at 4, 18 or 24 h after antigen
      challenge or 24 h after IL-4. Each challenged monkey lung was compared to a pool
      of normal, unchallenged monkey lungs. RESULTS: Of the approximately 40,000 cDNAs
      represented on the microarray, expression levels of 169 changed by more than 2.5
      fold in at least one of the pairwise probe comparisons; these cDNAs encoded 149
      genes, of which two thirds are known genes. The largest number of regulated genes
      was observed 4 h after challenge. Confirmation of differential expression in the
      original tissue was obtained for 95% of a set of these genes using real-time PCR.
      Cluster analysis revealed at least five groups of genes with unique expression
      patterns. One cluster contained genes for several chemokine mediators including
      eotaxin, PARC, MCP-1 and MCP-3. Genes involved in tissue remodeling and
      antioxidant responses were also identified as regulated by antigen and IL-4 or by
      antigen only. CONCLUSION: This study provides a large-scale profile of gene
      expression in the primate lung following allergen or IL-4 challenge. It shows
      that microarrays, with real-time PCR, are a powerful tool for identifying and
      validating differentially expressed genes in a disease model.

PMID- 12049662
TI  - Doxycycline-induced expression of sense and inverted-repeat constructs modulates
      phosphogluconate mutase (Pgm) gene expression in adult Drosophila melanogaster.
AB  - BACKGROUND: A tetracycline-regulated (conditional) system for RNA interference
      (RNAi) would have many practical applications. Such a strategy was developed
      using RNAi of the gene for phosphogluconate mutase (Pgm). Pgm is a candidate
      lifespan regulator: PgmS allele frequency is increased by selection for increased
      lifespan, whereas PgmM and PgmF allele frequencies are decreased. RESULTS: The
      Pgm alleles were cloned and sequenced and were found to differ by amino-acid
      substitutions consistent with the relative electrophoretic mobilities of the
      proteins. The 'tet-on' doxycycline-regulated promoter system was used to
      overexpress PgmS in a wild-type (PgmM) background. Enzyme activity increases of
      two- to five-fold were observed in five independent transgenic lines. Tet-on was
      also used to drive expression of an inverted-repeat fragment of Pgm coding
      region. The inverted-repeat transcript was expected to form a dsRNA hairpin,
      induce RNAi, and thereby reduce endogenous Pgm gene expression at the RNA level.
      Endogenous Pgm RNA levels in adult flies were found to be reduced or eliminated
      by doxycycline treatment in five independent inverted-repeat transgenic lines.
      Our results show that doxycycline-regulated expression of inverted-repeat
      constructs can cause a conditional reduction in specific gene expression. The
      effect of sense and inverted-repeat construct expression on lifespan was assayed
      in multiple transgenic lines. Under the conditions tested, altered Pgm gene
      expression had no detectable effect on adult Drosophila lifespan. CONCLUSIONS: A
      system for conditional RNAi in Drosophila adults shows promise for assay of gene
      functions during aging. Our results indicate that Pgm does not have a simple
      strong effect on longevity.

PMID- 12049663
TI  - How many replicates of arrays are required to detect gene expression changes in
      microarray experiments? A mixture model approach.
AB  - BACKGROUND: It has been recognized that replicates of arrays (or spots) may be
      necessary for reliably detecting differentially expressed genes in microarray
      experiments. However, the often-asked question of how many replicates are
      required has barely been addressed in the literature. In general, the answer
      depends on several factors: a given magnitude of expression change, a desired
      statistical power (that is, probability) to detect it, a specified Type I error
      rate, and the statistical method being used to detect the change. Here, we
      discuss how to calculate the number of replicates in the context of applying a
      nonparametric statistical method, the normal mixture model approach, to detect
      changes in gene expression. RESULTS: The methodology is applied to a data set
      containing expression levels of 1,176 genes in rats with and without pneumococcal
      middle-ear infection. We illustrate how to calculate the power functions for 2,
      4, 6 and 8 replicates. CONCLUSIONS: The proposed method is potentially useful in
      designing microarray experiments to discover differentially expressed genes. The
      same idea can be applied to other statistical methods.

PMID- 12049664
TI  - The GOLD domain, a novel protein module involved in Golgi function and secretion.
AB  - BACKGROUND: Members of the p24 (p24/gp25L/emp24/Erp) family of proteins have been
      shown to be critical components of the coated vesicles that are involved in the
      transportation of cargo molecules from the endoplasmic reticulum to the Golgi
      complex. The p24 proteins form hetero-oligomeric complexes and are believed to
      function as receptors for specific secretory cargo. RESULTS: Using sensitive
      sequence-profile analysis methods, we identified a novel beta-strand-rich domain,
      the GOLD (Golgi dynamics) domain, in the p24 proteins and several other proteins
      with roles in Golgi dynamics and secretion. This domain is predicted to mediate
      diverse protein-protein interactions. Other than in the p24 proteins, the GOLD
      domain is always found combined with lipid- or membrane-association domains such
      as the pleckstrin homology (PH), Sec14p and FYVE domains. CONCLUSIONS: The
      identification of the GOLD domain could aid in directed investigation of the role
      of the p24 proteins in the secretion process. The newly detected group of GOLD
      domain proteins, which might simultaneously bind membranes and other proteins,
      point to the existence of a novel class of adaptors that could have a role in the
      assembly of membrane-associated complexes or in regulating assembly of cargo into
      membranous vesicles.

PMID- 12049665
TI  - Evolution of gene fusions: horizontal transfer versus independent events.
AB  - BACKGROUND: Gene fusions can be used as tools for functional prediction and also
      as evolutionary markers. Fused genes often show a scattered phyletic
      distribution, which suggests a role for processes other than vertical inheritance
      in their evolution. RESULTS: The evolutionary history of gene fusions was studied
      by phylogenetic analysis of the domains in the fused proteins and the orthologous
      domains that form stand-alone proteins. Clustering of fusion components from
      phylogenetically distant species was construed as evidence of dissemination of
      the fused genes by horizontal transfer. Of the 51 examined gene fusions that are
      represented in at least two of the three primary kingdoms (Bacteria, Archaea and
      Eukaryota), 31 were most probably disseminated by cross-kingdom horizontal gene
      transfer, whereas 14 appeared to have evolved independently in different kingdoms
      and two were probably inherited from the common ancestor of modern life forms. On
      many occasions, the evolutionary scenario also involves one or more secondary
      fissions of the fusion gene. For approximately half of the fusions, stand-alone
      forms of the fusion components are encoded by juxtaposed genes, which are known
      or predicted to belong to the same operon in some of the prokaryotic genomes.
      This indicates that evolution of gene fusions often, if not always, involves an
      intermediate stage, during which the future fusion components exist as juxtaposed
      and co-regulated, but still distinct, genes within operons. CONCLUSION: These
      findings suggest a major role for horizontal transfer of gene fusions in the
      evolution of protein-domain architectures, but also indicate that independent
      fusions of the same pair of domains in distant species is not uncommon, which
      suggests positive selection for the multidomain architectures.

PMID- 12049666
TI  - Lateral gene transfer and parallel evolution in the history of glutathione
      biosynthesis genes.
AB  - BACKGROUND: Glutathione is found primarily in eukaryotes and in Gram-negative
      bacteria. It has been proposed that eukaryotes acquired the genes for glutathione
      biosynthesis from the alpha-proteobacterial progenitor of mitochondria. To
      evaluate this, we have used bioinformatics to analyze sequences of the
      biosynthetic enzymes gamma-glutamylcysteine ligase and glutathione synthetase.
      RESULTS: Gamma-glutamylcysteine ligase sequences fall into three groups:
      sequences primarily from gamma-proteobacteria; sequences from non-plant
      eukaryotes; and sequences primarily from alpha-proteobacteria and plants.
      Although pairwise sequence identities between groups are insignificant, conserved
      sequence motifs are found, suggesting that the proteins are distantly related.
      The data suggest numerous examples of lateral gene transfer, including a transfer
      from an alpha-proteobacterium to a plant. Glutathione synthetase sequences fall
      into two distinct groups: bacterial and eukaryotic. Proteins in both groups have
      a common structural fold, but the sequences are so divergent that it is uncertain
      whether these proteins are homologous or arose by convergent evolution.
      CONCLUSIONS: The evolutionary history of the glutathione biosynthesis genes is
      more complex than anticipated. Our analysis suggests that the two genes in the
      pathway were acquired independently. The gene for gamma-glutamylcysteine ligase
      most probably arose in cyanobacteria and was transferred to other bacteria,
      eukaryotes and at least one archaeon, although other scenarios cannot be ruled
      out. Because of high divergence in the sequences, the data neither support nor
      refute the hypothesis that the eukaryotic gene comes from a mitochondrial
      progenitor. After acquiring gamma-glutamylcysteine ligase, eukaryotes and most
      bacteria apparently recruited a protein with the ATP-grasp superfamily structural
      fold to catalyze synthesis of glutathione from gamma-glutamylcysteine and
      glycine. The eukaryotic glutathione synthetase did not evolve directly from the
      bacterial glutathione synthetase.

PMID- 12049667
TI  - Beyond the proteome: non-coding regulatory RNAs.
AB  - A variety of RNA molecules have been found over the last 20 years to have a
      remarkable range of functions beyond the well-known roles of messenger, ribosomal
      and transfer RNAs. Here, we present a general categorization of all non-coding
      RNAs and briefly discuss the ones that affect transcription, translation and
      protein function.

PMID- 12049669
TI  - Selection and gene duplication: a view from the genome.
AB  - Immediately after a gene duplication event, the duplicate genes have redundant
      functions. Is natural selection therefore completely relaxed after duplication?
      Does one gene evolve more rapidly than the other? Several recent genome-wide
      studies have suggested that duplicate genes are always under purifying selection
      and do not always evolve at the same rate.

PMID- 12049668
TI  - The diversity of acetylated proteins.
AB  - Acetylation of proteins, either on various amino-terminal residues or on the
      epsilon-amino group of lysine residues, is catalyzed by a wide range of
      acetyltransferases. Amino-terminal acetylation occurs on the bulk of eukaryotic
      proteins and on regulatory peptides, whereas lysine acetylation occurs at
      different positions on a variety of proteins, including histones, transcription
      factors, nuclear import factors, and alpha-tubulin.

PMID- 12049670
TI  - Wheat functional genomics and engineering crop improvement.
AB  - Genetic mapping and determination of the organization of the wheat genome are
      changing the wheat-breeding process. New initiatives to analyze the expressed
      portion of the wheat genome and structural analysis of the genomes of Arabidopsis
      and rice are increasing our knowledge of the genes that are linked to key
      agronomically important traits.

PMID- 12049671
TI  - Targeting fragile X.
AB  - Ten years after the identification of the gene responsible for fragile X
      syndrome, recent studies have revealed a list of mRNAs bound by the fragile X
      gene product and have identified specific sequences required for the interaction
      between the fragile X protein and its targets. These results are a breakthrough
      in understanding why absence of the fragile X protein leads to mental
      retardation.

PMID- 12049672
TI  - The ADF/cofilin family: actin-remodeling proteins.
AB  - The ADF/cofilins are a family of actin-binding proteins expressed in all
      eukaryotic cells so far examined. Members of this family remodel the actin
      cytoskeleton, for example during cytokinesis, when the actin-rich contractile
      ring shrinks as it contracts through the interaction of ADF/cofilins with both
      monomeric and filamentous actin. The depolymerizing activity is twofold:
      ADF/cofilins sever actin filaments and also increase the rate at which monomers
      leave the filament's pointed end. The three-dimensional structure of ADF/cofilins
      is similar to a fold in members of the gelsolin family of actin-binding proteins
      in which this fold is typically repeated three or six times; although both
      families bind polyphosphoinositide lipids and actin in a pH-dependent manner,
      they share no obvious sequence similarity. Plants and animals have multiple
      ADF/cofilin genes, belonging in vertebrates to two types, ADF and cofilins. Other
      eukaryotes (such as yeast, Acanthamoeba and slime moulds) have a single
      ADF/cofilin gene. Phylogenetic analysis of the ADF/cofilins reveals that, with
      few exceptions, their relationships reflect conventional views of the
      relationships between the major groups of organisms.

PMID- 12049674
TI  - Clinical and immunohistochemical study of eight cases with thymic carcinoma.
AB  - BACKGROUND: Thymic carcinoma is a rare neoplasm with extremely poor prognosis. To
      evaluate the biological characteristics of thymic carcinoma, we reviewed 8
      patients. METHODS: There were 2 men and 6 women: ages ranged from 19 to 67 years
      old (mean 54.8 years). None of these patients had concomitant myasthenia gravis
      and pure red cell aplasia. No patient had stage I disease, 1 stage II, 5 stage
      III, and 2 stage IV. The pathologic subtypes of thymic carcinoma included 5
      squamous cell carcinomas, 1 adenosquamous cell carcinomas, 1 clear cell
      carcinoma, and 1 small cell carcinoma. Immunohistochemical study was performed
      using antibodies against p53, bcl-2, Ki-67, carcinoembryonic antigen (CEA),
      epithelial membrane antigen (EMA), nm23-H1, vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (FGF-2) and factor VIII. RESULTS: Curative
      resection could be done in 4 patients (50%). Our data indicates a trend toward an
      association between complete resection and patient survival. Expression of p53,
      bcl-2, CEA, EMA, nm23-H1, VEGF and FGF-2 was detected in 5/8, 3/8, 4/8, 5/8, 6/8,
      5/8 and 3/8, respectively. Mean Ki-67 labeling index and microvessel density was
      7.01 and 34.36 (per 200x field), respectively. When compared with our previous
      studies, immunohistochemical staining of these proteins in thymomas, the
      expression rates of these proteins in thymic carcinomas were higher than those in
      thymomas. CONCLUSIONS: In this small series, it is suggested that a complete
      resection suggests a favorable result. Immunohistochemical results reveal that
      the expression of these proteins might indicate the aggressiveness of thymic
      carcinoma.

PMID- 12049675
TI  - Dynamic contrast-enhanced magnetic resonance imaging of the sarcopenic muscle.
AB  - BACKGROUND: Studies about capillarity of the aged muscle provided conflicting
      results and no data are currently available about the magnetic resonance imaging
      (MRI) in vivo characteristics of the microvascular bed in aged rats. We have
      studied age-related modifications of the skeletal muscle by in vivo T2
      relaxometry and dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) at
      high field intensity (4.7 T). The aim of the work was to test the hypothesis that
      the ageing process involves microvessels in skeletal muscle. METHODS: The study
      was performed in 4-month-old (n = 6) and 20-month-old (n = 6) rats. RESULTS: At
      MRI examination, the relaxation time T2 of the gastrocnemius muscle showed no
      significant difference between these two groups. The kinetic of contrast
      penetration in the tissue showed that in 4-month-old rats the enhancement values
      of the signal intensity at different time-points were significantly higher than
      those found in senescent rats. CONCLUSION: The reported finding suggests that
      there is a modification of the microcirculatory function in skeletal muscle of
      aged rats. This work also demonstrates that CE-MRI allows for an in vivo
      quantification of the multiple biological processes involving the skeletal muscle
      during aging. Therefore, CE-MRI could represent a further tool for the follow up
      of tissue modification and therapeutic intervention both in patients with
      sarcopenia and in experimental models of this pathology.

PMID- 12049673
TI  - Sildenafil (Viagra) for male erectile dysfunction: a meta-analysis of clinical
      trial reports.
AB  - BACKGROUND: Evaluation of company clinical trial reports could provide
      information for meta-analysis at the commercial introduction of a new technology.
      METHODS: Clinical trial reports of sildenafil for erectile dysfunction from
      September 1997 were used for meta-analysis of randomised trials (at least four
      weeks duration) and using fixed or dose optimisation regimens. The main outcome
      sought was an erection, sufficiently rigid for penetration, followed by
      successful intercourse, and conducted at home. RESULTS: Ten randomised controlled
      trials fulfilled the inclusion criteria (2123 men given sildenafil and 1131
      placebo). NNT or NNH were calculated for important efficacy, adverse event and
      discontinuation outcomes. Dose optimisation led to at least 60% of attempts at
      sexual intercourse being successful in 49% of men, compared with 11% with
      placebo; the NNT was 2.7 (95% confidence interval 2.3 to 3.3). For global
      improvement in erections the NNT was 1.7 (1.6 to 1.9). Treatment-related adverse
      events occurred in 30% of men on dose optimised sildenafil compared with 11% on
      placebo; the NNH was 5.4 (4.3 to 7.3). All cause discontinuations were less
      frequent with sildenafil (10%) than with placebo (20%). Sildenafil dose
      optimisation gave efficacy equivalent to the highest fixed doses, and adverse
      events equivalent to the lowest fixed doses. CONCLUSION: This review of clinical
      trial reports available at the time of licensing agreed with later reviews that
      had many more trials and patients. Making reports submitted for marketing
      approval available publicly would provide better information when it was most
      needed, and would improve evidence-based introduction of new technologies.

PMID- 12049676
TI  - Diagnostic strategies for C-reactive protein.
AB  - BACKGROUND: Serum C-reactive protein (CRP) has been identified in prospective
      epidemiological research as an independent risk marker for cardiovascular
      disease. In this paper, short-term biological variation of CRP is documented and
      a strategy to test the reliability of a single CRP sample is proposed. METHODS:
      Data were obtained from three groups of healthy volunteers: men, no oral
      contraceptives (OC-)using women and OC-using women. Blood samples were obtained 3
      times in men and twice in women during a workweek. RESULTS AND DISCUSSION: CRP
      values were highest in the OC-using women, followed by the men, and lowest in the
      no OC-using women. Averaged over the three groups the within-subject coefficients
      of variation (CVi) was 49.24% for CRP, and 29.90% for lnCRP. Using the repeated
      measures, individual samples were identified that reflected a 'suspicious'
      unreliable high value, i.e. a value that was more than 2 standard deviations
      higher than the lowest value obtained from the same subject. In an a posteriori
      analysis, three strategies to identify these suspicious high CRP values were then
      tested. In terms of maximizing detection of suspicious values and minimizing
      unnecessary resampling, best results were obtained for the most pragmatic
      criterion of using an absolute level, stratified for gender, and OC-use, to
      decide whether a second sample should be obtained. CONCLUSION: A single high CRP
      value must be followed by re-sampling when it is above 1.75 mg/l for men, above
      1.00 mg/l for no OC-using women, and above 2.00 mg/l for OC-using women.

PMID- 12049677
TI  - Heart rate variability: recent developments.

PMID- 12049678
TI  - Randomized study of early intravenous esmolol versus oral beta-blockers in
      preventing post-CABG atrial fibrillation in high risk patients identified by
      signal-averaged ECG: results of a pilot study.
AB  - BACKGROUND: Patients with prolonged signal-averaged ECG have four times higher
      risk for development of atrial fibrillation (AF) after coronary artery bypass
      surgery (CABG). Incidence of AF is reduced, but not eliminated by prophylaxis
      with beta-blockers. The limitations of prophylaxis with oral beta-blockers may be
      related to the delayed effect of oral therapy. We performed a pilot study of the
      efficacy of early intravenous esmolol and an oral beta-blocker regimen for
      prevention of postoperative AF. METHODS: Fifty patients referred for CABG and
      considered to be at high risk for postoperative AF on the basis of prolonged
      signal-averaged ECG P wave duration > 140 ms were randomized to receive either a
      24-hour infusion of esmolol 6-18 hours after CABG, at an average dose 67 +/- 7
      microg/kg/min, followed by oral beta-blockers versus oral beta-blockers only
      beginning on postoperative day 1. RESULTS: Seven of 27 patients (26%) in the
      esmolol group and 6 of 23 patients (26%) in the oral beta-blocker group developed
      postoperative AF, P = NS. The mean time of onset of AF (2.7 +/- 0.5 vs 2.7 +/-
      0.3 postoperative day, P = NS) and the median duration of AF (10 [2192] vs 7
      [1.16] hours, P = NS) were similar between the two groups. Eleven (41%) patients
      treated with esmolol developed adverse events (hypotension: 8, bradycardia
      requiring temporary pacing: 2, left ventricular failure:1 patient) as compared to
      only one patient (4%) in the beta-blocker group who developed hypotension, P =
      0.006. CONCLUSIONS: This randomized controlled pilot study suggests that
      intravenous esmolol is less well tolerated and offers no advantages to standard
      beta-blocker in preventing AF after CABG.

PMID- 12049679
TI  - Patients with persistent atrial fibrillation taking oral verapamil exhibit a
      lower atrial frequency on the ECG.
AB  - BACKGROUND: While there is agreement that verapamil attenuates the AF- induced
      refractory period shortening when given before AF induction, controversy exists
      regarding its effects when given after the onset of persistent AF. This study
      aimed to compare atrial fibrillatory frequency obtained from the surface ECG in
      patients with persistent atrial fibrillation (AF) with oral verapamil treatment
      to those without this treatment. METHODS AND RESULTS: Surface ECG recordings were
      performed in 57 patients (34 male, 23 female, mean age 59 +/- 11 years) with
      persistent AF (> 7 days). The frequency content of the fibrillatory baseline was
      quantified using digital signal processing (filtering, QRST complex averaging and
      subtraction, Fourier transformation). In 27 patients with verapamil treatment
      (120 or 240 mg/day for at least 7 days) mean fibrillatory frequency measured 6.4
      +/- 0.2 Hz, compared to 7.0 +/- 0.4 Hz (P = 0.012) in 30 patients without
      verapamil. In a subset of 20 randomly selected patients (10 with, 10 without
      verapamil treatment) a 24-hour Holter ECG recording was performed and
      fibrillatory frequency determined at 4 PM, 10 PM, 4 AM, and 10 AM. While there
      was a significant frequency reduction in the verapamil treated patients at night
      (P = 0.011), it remained constant over time in the other patients. CONCLUSION: In
      patients with persistent AF, fibrillatory frequency assessed by spectral analysis
      of the surface ECG is lower in patients taking verapamil.

PMID- 12049680
TI  - What percent luminal stenosis should be used to define angiographic coronary
      artery disease for noninvasive test evaluation?
AB  - BACKGROUND: There has been controversy over what is the best angiographic luminal
      dimension criterion associated with ischemia for evaluating diagnostic tests. If
      one assumes that ST-segment depression or scores are indicators of ischemia, then
      whatever angiographic criteria best discriminates those with ischemic and
      nonischemic responses would be the best angiographic marker for ischemia. To
      study this, we calculated the area under the ROC curves for ST depression and
      scores at different angiographic cut-points in order to determine the best
      angiographic cut-point for defining ischemia-producing coronary disease. METHODS:
      Twelve hundred and seventy-six consecutive males without prior MI with a mean age
      of 59 +/- 11 years who had undergone exercise testing and coronary angiography
      were analyzed in this study. We calculated the number of patients of this
      population that would be considered to have coronary artery disease at different
      cut-points for angiographic luminal stenosis. For example, 59% of the patients
      had significant CAD when disease was defined as 50% or greater coronary lumen
      stenosis of any coronary vessel while 49% of the patients had significant CAD
      when disease was defined as 70% or greater coronary lumen stenosis. Cut-points
      were considered between 40 to 100% coronary lumen stenosis. ROC analysis was then
      performed comparing ST depression and treadmill scores at each of these cut
      points. RESULTS: The cut-point for coronary lumen stenosis that returned the
      highest AUC for ST depression and scores was between 70 and 80% coronary luminal
      stenosis. However, the difference between the 50% and 75% luminal stenosis
      criteria was minimal. CONCLUSION: It appears that the best cut-point for defining
      significant angiographic disease when evaluating diagnostic tests of ischemia is
      75% or greater coronary luminal stenosis.

PMID- 12049681
TI  - Effect of the final coronary arterial diameter after coronary angioplasty on
      heart rate variability responses.
AB  - BACKGROUND: Autonomic nervous system dysfunction and reduced heart rate
      variability (HRV) after percutaneous transluminal coronary angioplasty (PTCA)
      were reported in patients with coronary artery disease. However, factors related
      to reduced HRV are not clearly demonstrated. The aim of the present study was to
      assess the relationship between HRV indices and the final coronary arterial
      luminal diameter after PTCA. METHODS: Twenty-seven patients (23 male, 4 female,
      mean age: 52.5 +/- 7.1 years) with single vessel disease were included in the
      study. PTCA was performed in all patients. Low-frequency power (LFP), high
      frequency power (HFP), and total power (TP) were calculated by using frequency
      domain analysis of HRV. All examinations were performed 24 hours before, and 24
      hours, 10 days, and 30 days after PTCA. The patients were divided into groups
      according to the PTCA restenosis risk score, the degree of dilatation, and
      revascularization after coronary angioplasty. RESULTS: The groups were comparable
      for age, gender, and coronary artery risk factors. HRV was found to be reduced in
      76% of patients. Reduction in HRV after PTCA was significantly related to the
      PTCA risk score and the degree of revascularization (r = 0.48, P < 0.01 and r =
      0.50, P < 0.008). Reduction in HRV was more significant in patients with previous
      myocardial infarction (P < 0.05). Recovery of HRV occurred on the tenth day after
      PTCA. CONCLUSION: Transient and rapidly recovered, especially parasympathetically
      modulated HRV reduction occurred after PTCA in patients with single-vessel
      disease. HRV reduction is associated with PTCA restenosis risk score and the
      degree of revascularization as invasive feature of angioplasty, hence it may be
      related to reperfusion.

PMID- 12049682
TI  - Relationship between changes in R-wave amplitude during left ventriculography and
      the seriousness of coronary heart disease.
AB  - Serious complications, such as myocardial infarction or death, may occur
      particularly in patients with severe coronary heart disease during coronary
      angiographies. Therefore, prediction of severe coronary heart disease before or
      during the initial steps of the procedure can provide a decrease in frequency of
      such complications. To predict the seriousness of coronary heart disease during
      left ventriculography, before, during, and after the application of contrast
      matter, electrocardiography (ECG) records were taken and R-wave amplitudes were
      measured. Lead DII was used for calculations. The patients were classified
      according to vessel lesions and were compared with the control group. Before and
      after left ventriculography, there was no significant difference between the
      groups with normal coronary arteries and one, two, or three vessel lesions.
      Although there was no significant difference obtained from the comparison of the
      control group and the groups with one-vessel and two-vessel lesions (9.7 mm, 9.2
      mm, 10.1 mm, respectively, P > 0.05); there was statistical difference between
      the group with three-vessel lesions and the control group during left
      ventriculography (6.4 mm, 9.7 mm, respectively, P < 0.05). Nonionic contrast
      material was used in all procedures. The decrement of R-wave amplitude that is
      observed during left ventriculography can predict three-vessel disease, which is
      a more serious condition for the patients. These patients should be monitored
      more carefully during coronary angiographies.

PMID- 12049683
TI  - Differentiation of narrow QRS complex tachycardia types using the 12-lead
      electrocardiogram.
AB  - BACKGROUND: Previous studies have shown that only 80% of narrow QRS
      supraventricular tachycardia (SVT) types can be differentiated by standard 12
      lead electrocardiographic (ECG) criteria. This study was designed to determine
      the value of some new ECG criteria in differentiating narrow QRS SVT. METHODS AND
      RESULTS: 120 ECGs demonstrating paroxysmal narrow QRS complex tachycardia (QRS <
      or = 0.11 ms and rate > 120 beats/min) were analyzed. Forty atrioventricular
      reciprocating tachycardia (AVRT), 70 atrioventricular nodal reentrant tachycardia
      (AVNRT), and 10 atrial tachycardia defined with electrophysiologic study (EPS)
      consisted the study group. Eight surface ECG criteria were found to be
      significantly different between tachycardia types by univariate analysis. P waves
      separate from the QRS complex were observed more frequently in AVRT (70%) and
      atrial tachycardia (80%). Pseudo r' deflection in lead V(1), pseudo S wave in
      inferior leads, and cycle length alternans were more common in AVNRT (55, 20, and
      6%, respectively). QRS alternans was also present during AVRT (28%). ST-segment
      depression (> or = 2 mm) or T-wave inversion, or both, were present more often in
      AVRT (60%) than in AVNRT (27%). During sinus rhythm, manifest preexcitation was
      observed more often in patients with AVRT (42%). When a P wave was present, RP/PR
      interval ratio > 1 was more common in atrial tachycardia (90%). By multivariate
      analysis, presence of a P wave separate from the QRS complex, pseudo r'
      deflection in lead V(1), QRS alternans, preexcitation during sinus rhythm, ST
      segment depression > 2 mm or T-wave inversion, or both, were independent
      predictors of tachycardia type. CONCLUSIONS: Several new ECG criteria may be
      useful in differentiation of SVT types. Prediction of mechanism prior to EPS may
      provide additional benefits concerning the fluoroscopic exposure time and cardiac
      catheterization procedure.

PMID- 12049684
TI  - Apnea-related heart rate variability and its clinical utility in congestive heart
      failure outpatients.
AB  - BACKGROUND: Cheyne-Stokes breathing (CSB) is an abnormal cyclical pattern of
      respiratory fluctuations observed during sleep in congestive heart failure (CHF)
      of poor prognosis. We examined the clinical usefulness of CSB screening using the
      heart rate variability (HRV) data from the ambulatory electrocardiogram. METHODS:
      We monitored ambulatory electrocardiograms and respiration simultaneously in 86
      heart disease patients of both sexes, aged 57 +/- 1 years. HRV was analyzed by
      the maximum entropy method during the sleeping period (11 PM-5 AM). The 43 CHF
      patients underwent a 1-year follow-up study. RESULTS: In the power spectra of the
      HRV, peaks were observed within the CSB band (0.005 to 0.03 Hz). Statistically
      significant differences in HRV were observed between CSB patients and CSB-free
      patients in very low frequency (VLF) (P = 0.04), VLF/total frequency (TF) (P =
      0.02), CSB (P = 0.01), CSB/TF (P = 0.003), and CSB/VLF (P < 0.0001). Cardiac
      events occurred in 23% of patients, including cardiac death in two, and
      rehospitalization for aggravated CHF in eight. In a multivariate Cox regression
      analysis in which age, sex, ejection fraction, NYHA functional class, beta
      blocker use, and basic heart disease were included, absence of ACE inhibitor use
      (RR 5.5, 95% CI 1.0-31) and CSB/VLF > or =80% (RR 4.2, 95% CI 1.1-17) remained
      significant predictors of cardiac events. CONCLUSIONS: HRV can act as an
      indicator of the presence of CSB in CHF patients, and could therefore be used,
      under outpatient conditions, to identify a CHF patients with a poor prognosis.

PMID- 12049685
TI  - Effects of carvedilol on heart rate dynamics in patients with congestive heart
      failure.
AB  - BACKGROUND: Patients with congestive heart failure (CHF) have alterations in the
      traditional and nonlinear indices of heart rate (HR) dynamics, which have been
      associated with an increased risk of mortality. This study was designed to test
      the effects of carvedilol, a nonselective beta-blocker with alpha-1 blocking
      properties, on HR dynamics in patients with CHF. METHODS: We studied 15 patients
      with CHF secondary to ischemic or idiopathic cardiomyopathy who met the following
      inclusion criteria: NYHA functional class II-III, optimal conventional medical
      therapy, normal sinus rhythm, left ventricular ejection fraction (LVEF) of < 40%,
      and resting systolic blood pressure greater than 100 mmHg. The 6-minute corridor
      walk test, estimation of LVEF, and 24-hour Holter recording were performed at
      baseline and after 12 weeks of therapy with carvedilol. Traditional time and
      frequency domain measures and short-term fractal scaling exponent of HR dynamics
      were analyzed. RESULTS: After 12 weeks of therapy with carvedilol, the mean LVEF
      improved significantly (from 0.27 +/- 0.08 to 0.38 +/- 0.08, P < 0.001). The
      average HR decreased significantly (from 86 +/- 11 to 70 +/- 8 beats/min, P <
      0.001). The mean distance traveled in the 6-minute walk test increased
      significantly (from 177 +/- 44 to 273 +/- 55 m, P < 0.01). The frequency-domain
      indices (HF and LF), the time domain indices (rMSSD and PNN5 ), and the short
      term fractal scaling exponent increased significantly. The scaling exponent
      increased particularly among the patients with the lowest initial values (< 1.0),
      and the change in the fractal scaling exponent correlated with the change in
      ejection fraction (r = 0.63, P < 0.01). CONCLUSION: Carvedilol improves time and
      frequency domain indices of HR variability and corrects the altered scaling
      properties of HR dynamics in patients with CHF. It also improves LVEF and
      functional capacity. These specific changes in HR behavior caused by carvedilol
      treatment may reflect the normalization of impaired cardiovascular neural
      regulation of patients with CHF.

PMID- 12049686
TI  - Body surface potential mapping: historical background, present possibilities,
      diagnostic challenges.

PMID- 12049687
TI  - History of preexcitation: "A Case in Which the Vagus Influenced the Form of the
      Ventricular Complex of the Electrocardiogram".

PMID- 12049688
TI  - Location and clinical implications of high-degree atrioventricular block during
      dipyridamole infusion: a case report.
AB  - We describe a patient with bifascicular block, who developed transient high
      degree atrioventricular block during dipyridamole infusion. This patient was
      subsequently found to have significant His-Purkinje disease at electrophysiology
      study, and underwent permanent pacemaker implantation. Spontaneous
      atrioventricular block was documented during follow-up. This case report raises
      the issue of dipyridamole safety in patients with intraventricular conduction
      defects, and contributes an additional mechanism to the possible explanation of
      dipyridamole-induced atrioventricular block.

PMID- 12049690
TI  - [Clinico-hemodynamic study and treatment of 44 patients with primary pulmonary
      hypertension].
AB  - BACKGROUND: Primary pulmonary hypertension is a poorly understood disease with a
      difficult treatment. PATIENTS AND METHOD: Retrospective study of a series of 44
      patients suffering from pulmonary hypertension who were studied in our center
      between 1992 and 2000. RESULTS: At diagnosis, 6 (13%) patients were classified as
      having NYHA functional class I, 11 (25%) had class II, 25 (57%) had class III,
      and 2 had class IV. Mean pulmonary artery systolic pressure by echo-doppler was
      92 (range: 43-154) mmHg. Basal right catheterization showed a mean (SD) pulmonary
      artery pressure of 58 (18) mmHg, total basal pulmonary resistances of 1679
      (1,071) din/cm2 and cardiac index of 2.2 (1) 1/minute/m2. Five patients improved
      with anticoagulation and calcium channel blockers therapy. Since 1998, 11
      patients had been treated with continuous endovenous epoprostenol, yet only 3
      (27%) had significant clinical improvement. Survival at 5 years after diagnosis
      was 56%. At the end of study, 7 (70%) out of 10 patients who underwent pulmonary
      transplantation were alive (mean: 34, range: 3-62 months). CONCLUSIONS: Pulmonary
      hypertension is a disease with a poor prognosis. However, treatment with
      prostaglandins and pulmonary transplantation may lead to encouraging results.

PMID- 12049691
TI  - [Metabolic factors in school children population associated with adult
      cardiovascular mortality. Four provinces' study].
AB  - BACKGROUND: Environmental factors in early stages of life may contribute to adult
      cardiovascular disease. We have examined certain anthropometric and biochemical
      variables in children aged 6-7 years from four Spanish provinces with high
      differences in mortality due to ischemic heart disease (IHD). PATIENTS AND
      METHOD: We performed a cross-sectional survey of 1,255 children (50.3% males)
      attending schools in Cadiz and Murcia provinces with a relatively high IHD
      mortality and Madrid and Orense provinces with a relatively low IHD mortality.
      Weight, body mass index (BMI) and prevalence of obesity were analyzed, and plasma
      glucose and lipid levels were measured by standardized methods. RESULTS: Compared
      with children in the two low-IHD-mortality provinces, those in the two high-IHD
      mortality provinces had greater weight (p < 0.05) and BMI (p < 0.01) and higher
      prevalence of obesity (p < 0.01). Moreover, they had significantly higher (p <
      0.01) plasma glucose, triglyceride and apo A-I levels. CONCLUSIONS: The higher
      prevalence of overweight and obesity, along with higher plasma glucose and
      triglyceride levels, in provinces with high coronary artery disease mortality
      indicates that children from these provinces are metabolically different from
      those in provinces with low coronary artery disease mortality. These alterations
      may thus contribute to the different IHD mortality in adulthood.

PMID- 12049692
TI  - [Variations in the drug treatment of rheumatoid arthritis in Spain].
AB  - BACKGROUND: Variations in the use of healthcare resources can result in
      differences in the outcome of rheumatoid arthritis (RA). The emAR study was
      developed to determine variations in the management of socio-sanitary resources,
      including drugs use, in patients with this disorder. PATIENTS AND METHOD: The
      clinical records of 1,379 patients, randomly selected among all RA patients
      attended in Spanish hospitals, were reviewed. Information about prescription of
      disease modifying anti-rheumatic drugs (DMARD), non-steroidal anti-inflammatory
      drugs (NSAID), corticosteroids, analgesics, gastric protectors and drugs for
      osteoporosis was collected. In addition, socio-demographic- and disease-related
      information, as well as data from hospitals, medical units and responsible
      physicians were also obtained in each patient. RESULTS: There was a high level of
      DMARD and NSAID prescription that was associated with patient or disease
      characteristics. Treatment with corticosteroids, as well as with the remaining
      drugs, showed a substantial regional variability, which may be related to
      physician-associated variables as well as to patient- and disease-associated
      characteristics. CONCLUSIONS: Variability in the management of therapeutic
      resources in RA patients mainly depends on the characteristics of the patient or
      the disease. There is also a variation that is influenced by physician's
      characteristics; in some cases, the available scientific evidence may not support
      this variability.

PMID- 12049693
TI  - [Clinical evolution of a cohort of patients with Graves-Basedow disease treated
      with metimazole].
AB  - BACKGROUND: Prospective studies of Graves-Basedow disease in Spain are scarce.
      Our objective was to evaluate the clinical and biochemical evolution of a cohort
      of patients with Graves-Basedow disease. PATIENTS AND METHOD: 202 patients with
      Graves-Basedow disease diagnosed between January 1997 and June 1999. RESULTS:
      5.9% of patients received 131I and 2.5% underwent surgery after treatment with
      methimazole. A relapse was observed in 23.3% patients. In the survival analysis,
      significant differences with regard to the rate of relapse were observed
      according to the goitre degree. CONCLUSIONS: In our study, all patients reached
      remission with methimazole. There was a high rate of relapse following
      discontinuation of therapy within the first months. Goitre size at the time of
      diagnosis was a significant determining factor of relapse.

PMID- 12049694
TI  - [Aldosterone blockade in heart failure. So much for so little].

PMID- 12049695
TI  - [Praise of complexity].

PMID- 12049696
TI  - [Hyperthyroidism in the aged].

PMID- 12049697
TI  - [Recommendations of GESIDA/Spanish National Plan of AIDS on diagnosis and
      treatment of Kaposi's sarcoma and cervical cancer in HIV-infected patients].

PMID- 12049698
TI  - [HELLP syndrome associated to pulmonary thromboembolism and factor V Leiden].

PMID- 12049699
TI  - [Severe bacterial infections after prophylactic suppression of Pneumocystis
      carinii in HIV infected patients after CD4 lymphocyte recovery].

PMID- 12049701
TI  - [Gynecomastia secondary to rofecoxib].

PMID- 12049700
TI  - [Hyperthyroidism secondary to kelp tablets ingestias].

PMID- 12049702
TI  - [Mesenteric vasculitis and abdominal mass].

PMID- 12049703
TI  - [Factors associated with resistance to human immunodeficiency virus protease
      inhibitors].
AB  - BACKGROUND: To assess the risk factors associated with genotypic resistance to
      protease inhibitors (PI) in HIV-infected subjects with virologic failure despite
      highly active antiretroviral treatment (HAART). PATIENTS AND METHOD:
      Retrospective chart review including 47 consecutive patients with virologic
      failure despite PI-based HAART who had undergone a genotypic HIV-1 testing. The
      prevalence of genotypic resistance to PI was determined and several demographic,
      clinical and laboratory variables were compared between patients with and without
      genotypic resistance to those drugs. RESULTS: The entire nucleotide sequence of
      the protease gene was obtained in 43 of the 47 patients; 18 of them had genotypic
      resistance to PI. Genotypic resistance to PI was associated with a previous
      therapy with suboptimal antiretroviral regimens (OR = 10.2; 95% CI, 1.05-245.1; P
      = 0.02), duration of antiretroviral therapy longer than 18 months (OR = 13.3; 95%
      CI, 1.23-340.85; P = 0.01), greater number of antiretroviral regimens and drugs
      before the virologic failure (p < 0.01) and presence of the 184V mutation in the
      reverse transcriptase gene (OR = 5.6; 95% CI, 1.2-29.2; P = 0.02). There was no
      relationship between PI resistance and the risk group, viral load or CD4 cell
      count. In the multivariate analysis, previous therapy with suboptimal
      antiretroviral regimens was the better predictor of PI resistance (OR = 11.1; 95%
      CI, 1.04-117.47; P = 0.046). CONCLUSIONS: Patients treated with suboptimal
      antiretroviral activity regimens before starting HAART can be at greater risk of
      developing genotypic resistance to protease inhibitors.

PMID- 12049704
TI  - [Etiology of hospital-acquired infections in Spanish hospitals (EPINE, 1990
      1999)].
AB  - BACKGROUND: Clinical and demographic characteristics of patients, their
      interaction with pathogens and antimicrobial therapies are prompting changes in
      the epidemiology of hospital-acquired infections (HI). The knowledge of the
      etiology of hospital-acquired infections is valuable for the treatment of
      infected patients and for the prevention of HI. PATIENTS AND METHOD: We analyzed
      a series of 10 annual prevalence studies during the period 1990-1999 (EPINE
      project) in Spanish hospitals. Estimate of prevalence of infection was calculated
      by means of the percent distribution of every organism regarding overall
      identified organisms and infections. RESULTS: 40,550 HI were identified among
      484,013 patients (HI prevalence = 8.4%; 95% CI, 8.3-8.5%). Gram-positive organism
      predominated steadily in bloodstream and surgical wound infections, while gram
      negative bacilli predominated in respiratory and urinary tract infections. There
      was an increase in HI infections by Acinetobacter baumannii (from 1.9% in 1990 to
      3.6% in 1999; P < 0.001) and Candida albicans (from 2.4 to 3.2%; P < 0.001), as
      well as an increase in both HI and community-acquired infections by methicillin
      resistant Staphylococcus aureus [HI: from 4.7 to 40.2% (P < 0.001); community
      acquired: from 2.7 to 15.6% (P < 0.001)]. CONCLUSIONS: We observed some changes
      in the etiology of infections over the last decade: rates of methicillin
      resistant S. aureus hospital-acquired and community-acquired infections increased
      steadily and their initial rates multiplied by 8 and 6, respectively. Rates of HI
      caused by yeasts and A. baumannii increased also.

PMID- 12049705
TI  - [Antimicrobial use in Spanish hospitals (EPINE, 1990-1999)].
AB  - BACKGROUND: Monitoring of antimicrobial use and knowledge of prescription habits
      are some of the strategies recommended to contain the resistance to
      antimicrobials in hospitals. METHOD: We analyzed a series of 10 annual studies of
      prevalence during the period 1990-1999 (EPINE project) in Spanish hospitals.
      Estimates of antimicrobial use were calculated as the percent distribution of
      every antimicrobial related to the overall antimicrobials prescribed. RESULTS:
      Among 484,013 hospitalized patients, 34 to 36% were receiving antimicrobials
      (antibiotics > 90%). Amoxicillin-clavulanate use increased from 3.8% in 1990 up
      to 14.8% in 1999 (P < 0.01). Significant increases were also observed in the use
      of carbapenems (0.9 to 2.7%; P < 0.01), glycopeptides (1.7 to 3.7%; P < 0.01) and
      quinolones (8.5 to 11.3%; P < 0.01) though to a lesser degree. Conversely, the
      use of aminoglycosides decreased over the decade studied (15.8 to 9.4%; P <
      0.01). CONCLUSIONS: Even though the use of antimicrobials has increased over the
      last decade, current figures are within the ranges observed in other countries.
      The pattern of antibiotics use has changed during this period: while the use of
      aminoglycosides decreased, that of -lactams plus -lactamase inhibitors,
      quinolones and carbapenems increased.

PMID- 12049706
TI  - [Response degree of cholesterol LDL to feeding in males with hypercholesterolemia
      according to baseline value].
AB  - BACKGROUND: The response of plasma cholesterol to diet is modulated by endogenous
      and exogenous factors such as body mass, tobacco consumption, gender and the
      genetic background. Our purpose was to know whether the response degree depends
      on the concentration of cholesterol prior to the intervention and whether several
      polymorphisms modulating the cholesterol response to diet are actually involved
      in such response. PATIENTS AND METHOD: Seventy two males with
      hypercholesterolemia were administered three different 4-weeks duration diets.
      The first one was a saturated fat-enriched (SAT) diet. Then, in a randomized and
      crossed manner, subjects were categorized in two groups: one group received a
      diet with low fat but high complex carbohydrates contents (HCO); the another
      group received a monounsaturated fat-enriched diet (Mediterranean diet). In the
      third period, we inverted the diets of the previous period. We determined the
      prevalent genotypes of the following apoproteins: E, CIII, A-IV, A-I, B, A-IV
      360. RESULTS: The diet with low fat contents and the Mediterranean diet led to a
      significant decrease of total cholesterol, LDL-c and HDL-c. Those at the upper
      LDL-c tertile, after the SAT diet, were found to have statistically significant
      greater decreases (absolute and relative values) with the Mediterranean and HCO
      diet. In the multivariate analysis, the only variable with an effect on the
      modification of LDL-c, after shifting a SAT to any hypolipidemic diet, were the
      levels of LDL-c at the end of a SAT diet. The allelic frequency of different
      apoproteins in the hyper-respondent group was not different from that in the hypo
      respondent group (response displayed when going from a SAT period to any
      hypolipidemic diet). CONCLUSIONS: The decrease of LDL-c observed with
      hypolipidemic diets (low in fat contents or Mediterranean) was more significant
      in those individuals with hypercholesterolemia who had higher levels of LDL-c at
      the onset.

PMID- 12049707
TI  - [New diagnostic applications of magnetic resonance in neurology].

PMID- 12049708
TI  - [Consensus report on the diagnosis and treatment of fibromyalgia in Catalonia].

PMID- 12049709
TI  - [Secretion tumor markers: state of the art].

PMID- 12049710
TI  - [Diabetic foot ulcers and treatment with low molecular weight heparin].

PMID- 12049711
TI  - [Interleukin-1 genotype in mouthwash from patients with periodontal disease].

PMID- 12049712
TI  - [Galactorrhea induced by paroxetine].

PMID- 12049713
TI  - [Behr syndrome and hypergonadotropic hypogonadism].

PMID- 12049714
TI  - T cell development: bottoms-up.
AB  - An important but laborious approach to understanding the concepts underlying T
      cell lineage commitment is to characterize the cis-acting control elements
      governing the expression of CD4 and CD8. Previous studies on the CD4 gene have
      shown that lineage commitment information is directed by the intronic silencer;
      however, a similarly simple mechanism for controlling CD8 gene expression has not
      been uncovered. In this issue of Immunity, two groups have investigated the role
      of putative enhancers in the CD8 locus. The deletion of three different elements
      in the intergeneic region between CD8 beta and CD8 alpha provides evidence for
      control at the level of chromatin accessibility.

PMID- 12049715
TI  - Combined deletion of CD8 locus cis-regulatory elements affects initiation but not
      maintenance of CD8 expression.
AB  - Developmental stage-, subset-, and lineage-specific CD8 enhancers have been
      identified recently by transgenic reporter analyses. Enhancer E8(II) (CIV-4,5) is
      active in both immature double-positive thymocytes (DP) and mature CD8 single
      positive (SP) thymocytes and T cells, whereas E8(I) (CIII-1,2) directs expression
      only in mature cells. In mice lacking either E8(I) (CIII-1,2) or E8(II) (CIV
      4,5), there was no effect on CD8 expression in DP thymocytes. However, deletion
      of both enhancers resulted in variegated expression of CD8, with appearance of
      CD4(+)CD8(-) SP thymocytes expressing surface markers characteristic of DP
      thymocytes. Consequently, fewer mature CD8(+) T cells developed from the reduced
      pool of DP cells. These results suggest that the initiation of CD8 expression is
      mediated by cis-regulatory elements that are distinct from any that may be
      involved in maintenance of expression.

PMID- 12049716
TI  - Variegated expression of CD8 alpha resulting from in situ deletion of regulatory
      sequences.
AB  - The developmental and subset-specific expression of the CD8 genes is under the
      control of a complex array of regulatory elements distributed along the locus and
      characterized by DNaseI hypersensitivity. Here we describe the phenotype of mice
      in which hypersensitive sites 1 and 2 (HSS1 and 2) of DNaseI hypersensitive
      Cluster II (CII), which are located upstream of the CD8 alpha gene, were deleted
      by targeted homologous recombination of the endogenous locus. Knockout mice
      exhibit a variegated expression of the CD8 alpha gene, particularly among the
      immature CD4(+)8(+) TCR(lo) thymocyte population. We propose that HSS Cluster II
      regulatory elements are essential in ensuring initiation of chromatin remodeling
      and establishment of an open configuration in all developing thymocytes that
      undergo the double-negative to double-positive transition. Furthermore, these
      sequences contribute to the levels of expression of the CD8 alpha gene.

PMID- 12049717
TI  - Th2 lineage commitment and efficient IL-4 production involves extended
      demethylation of the IL-4 gene.
AB  - The relation of CpG methylation to gene silencing is well established, but the
      contribution of DNA demethylation to gene expression during cell differentiation
      remains unclear. We show that the IL-4 locus undergoes a complex series of
      methylation and demethylation steps during T helper cell differentiation. The 5'
      region of the IL-4 locus is hypermethylated in naive T cells and becomes
      specifically demethylated in Th2 cells, whereas a highly conserved DNase I
      hypersensitive region at the 3' end shows the converse behavior, being
      hypomethylated in naive T cells and becoming methylated during Th1
      differentiation. 5' demethylation is not required for chromatin remodeling or
      primary transcription of the IL-4 gene but is strongly associated with efficient,
      high-level induction of IL-4 transcripts by differentiated Th2 cells.

PMID- 12049718
TI  - Runx1 expression marks long-term repopulating hematopoietic stem cells in the
      midgestation mouse embryo.
AB  - Hematopoietic stem cells (HSCs) are first found in the aorta-gonad-mesonephros
      region and vitelline and umbilical arteries of the midgestation mouse embryo.
      Runx1 (AML1), the DNA binding subunit of a core binding factor, is required for
      the emergence and/or subsequent function of HSCs. We show that all HSCs in the
      embryo express Runx1. Furthermore, HSCs in Runx1(+/-) embryos are heterogeneous
      and include CD45(+) cells, endothelial cells, and mesenchymal cells. Comparison
      with wild-type embryos showed that the distribution of HSCs among these various
      cell populations is sensitive to Runx1 dosage. These data provide the first
      morphological description of embryonic HSCs and contribute new insight into their
      cellular origin.

PMID- 12049719
TI  - Hematopoietic stem cells localize to the endothelial cell layer in the
      midgestation mouse aorta.
AB  - The emergence of the first adult hematopoietic stem cells (HSCs) during mammalian
      ontogeny has been under intense investigation. It is as yet unresolved whether
      these first HSCs are derived from intraembryonic hemangioblasts, hemogenic
      endothelial cells, or other progenitors. Thus, to examine the spatial generation
      of functional HSCs within the mouse embryo, we used the well-known HSC marker,
      Sca-1, and a transgenic approach with an Ly-6A (Sca-1) GFP marker gene. Our
      results show that this transgene marker is expressed in all functional HSCs in
      the midgestation aorta. Immunohistology of aorta-gonads-mesonephros (AGM) regions
      show that GFP(+) cells are specifically localized to the endothelial layer lining
      the wall of the dorsal aorta but not to the mesenchyme, strongly suggesting that
      HSC activity arises within a few cells within the endothelium of the major
      vasculature.

PMID- 12049720
TI  - HSP70 protects against TNF-induced lethal inflammatory shock.
AB  - The heat shock (HS) response is a universal response activated after exposure to
      various stimuli. The major HS protein (HSP) is the 72 kDa HSP70 with strong
      homology in different eukaryotic species. We demonstrate that HS treatment of
      mice leads to a strong induction of HSP70 in several organs and confers
      significant protection against lethality induced by tumor necrosis factor (TNF).
      HS prevents high production of interleukin-6 and nitric oxide and reduces severe
      damage and apoptosis of the enterocytes in the bowel. Mice deficient in the
      inducible hsp70.1 gene were no longer protected by HS treatment. We show that HS
      can be applied successfully in an antitumor protocol based on TNF and interferon
      gamma, leading to a significant inhibition of lethality but not to a reduction of
      antitumoral capacity.

PMID- 12049721
TI  - Failure of trafficking and antigen presentation by CD1 in AP-3-deficient cells.
AB  - Endocytosed microbial antigens are primarily delivered to lysosomal compartments
      where antigen binding to MHC and CD1 molecules occurs in an acidic and
      proteolytically active environment. Signal-dependent delivery to lysosomes has
      been suggested for these antigen-presenting molecules, but molecular interactions
      with vesicular coat proteins and adaptors that direct their lysosomal sorting are
      poorly understood. Here CD1b but not other CD1 isoforms bound the AP-3 adaptor
      protein complex. In AP-3-deficient cells derived from patients with Hermansky
      Pudlak syndrome type 2 (HPS-2), CD1b failed to efficiently gain access to
      lysosomes, resulting in a profound defect in antigen presentation. Since MHC
      class II traffics normally in AP-3-deficient cells, defects in CD1b antigen
      presentation may account for recurrent bacterial infections in HPS-2 patients.

PMID- 12049722
TI  - Failure of HY-specific thymocytes to escape negative selection by receptor
      editing.
AB  - Editing of autoreactive antigen receptors by secondary V(D)J recombination
      efficiently rescues B lymphocyte precursors from apoptosis induced by negative
      selection, but its role has not been rigorously assessed in T cell development.
      We therefore generated a transgenic mouse model in which self-reactive thymocytes
      could edit their TCR by secondary recombination at the TCR alpha locus. For this
      purpose, the V alpha J alpha exon of a male-specific TCR was inserted into the
      TCR alpha locus followed by Cre-loxP-mediated deletion of the TCR delta locus. In
      this model, only few thymocytes escaped negative selection by change of
      specificity, probably through recombination before encounter of autoantigen. In
      the absence of the restricting MHC element, however, developing thymocytes
      replaced the inserted TCR alpha exon efficiently.

PMID- 12049724
TI  - Growth factor independent-1 induced by IL-4 regulates Th2 cell proliferation.
AB  - IL-4 is important in Th2 differentiation and in cell expansion. Stat6 is
      necessary and sufficient for both functions. Although Gata3 is critical for Th2
      polarization, it is not sufficient to mediate IL-4-driven cell expansion. We
      report that growth factor independent-1 (Gfi-1), a Stat6-dependent
      transcriptional repressor, strikingly increases Th2 cell expansion by promoting
      proliferation and preventing apoptosis. Cells infected with a Gfi-1 retrovirus
      show striking enhancement of IL-2-induced Stat5 phosphorylation and repression of
      p27(Kip-1) expression, suggesting a potential mechanism for the Gfi-1 growth
      effect. The synergy of Gfi-1 and Gata3 provides a mechanism through which IL-4
      could selectively promote Th2 cell expansion.

PMID- 12049723
TI  - CD154-dependent priming of diabetogenic CD4(+) T cells dissociated from
      activation of antigen-presenting cells.
AB  - We followed the fate of K(d)- or I-A(g7)-restricted beta cell-autoreactive T
      cells in monoclonal TCR-transgenic NOD mice expressing or lacking CD154. 8.3
      NOD.RAG-2(-/-)/CD154(-/-) mice, which bear autoreactive CD8(+) T cells, developed
      diabetes with the same incidence and tempo as 8.3-NOD.RAG-2(-/-)/CD154(+) mice.
      Recruitment of CD154(-/-) 8.3-CD8(+) CTL was accelerated by CD154(+)CD4(+) T
      cells, by expression of a B7.1 transgene in beta cells or by treatment of the
      mice with CpG-DNA or an agonistic anti-CD40 antibody. In contrast, the
      autoreactive CD4(+) T cells maturing in 4.1-NOD.RAG-2(-/-) mice lost their
      diabetogenic potential if they lacked CD154, even in the presence of
      CD154(+)CD4(+) T cells, B7.1 molecules on beta cells, CpG-DNA treatment, or
      systemic CD40 ligation. These results demonstrate the existence of a novel, CD154
      dependent pathway of CD4(+) T cell activation that is independent of CD40
      mediated activation of APCs.

PMID- 12049725
TI  - The dispersal of mucosal memory B cells: evidence from persistent EBV infection.
AB  - We have used latent infection with the human herpesvirus Epstein-Barr virus to
      track the dispersal of memory B cells from the mucosal lymphoid tissue of
      Waldeyer's ring (tonsils/adenoids). EBV is evenly distributed between the memory
      compartments of Waldeyer's ring and the peripheral blood. However, it has an
      approximately 20-fold higher preference for Waldeyer's ring over the spleen or
      mesenteric lymph nodes. These observations are consistent with a model whereby
      the virus preferentially establishes persistent infection within memory B cells
      from Waldeyer's ring. The virus then colonizes the entire peripheral lymphoid
      system, at a low level, by trafficking with these memory B cells as they
      circulate through the body and back to Waldeyer's ring. This pathway may reflect
      that of normal memory B cells derived from nasopharyngeal and other mucosal lymph
      nodes.

PMID- 12049726
TI  - HDAC's at work: everyone doing their part.
AB  - The interplay between histone acetyltransferases (HATs) and histone deacetylases
      (HDACs) is key to the dynamics of chromatin structure and function. A recent
      report of genome-wide, microarray maps of histone acetylation has uncovered the
      intragenic targets for six different yeast HDACs and has led to the discovery of
      new heterochromatin-like domains.

PMID- 12049727
TI  - The SCF ubiquitin ligase: an extended look.
AB  - The SCF E3 ubiquitin ligases select specific proteins for ubiquitination (and
      typically destruction) by coupling variable adaptor (F box) proteins that bind
      protein substrates to a conserved catalytic engine containing a cullin, Cul1, and
      the Rbx1/Roc1 RING finger protein. A new crystal structure of the SCF(Skp2)
      ubiquitin ligase shows the molecular organization of this complex and raises
      important questions as to how substrate ubiquitination is accomplished.

PMID- 12049728
TI  - RNAi targeting an animal virus: news from the front.
AB  - Although many eukaryotic organisms exhibit RNA interference, its role as an
      antiviral pathway is established only for plants. A recent paper demonstrates
      that it also acts in animals, and reveals a viral suppressor of this process.

PMID- 12049729
TI  - Fine-tuning the RAS signaling pathway: Zn(2+) makes the difference.
AB  - In the May, 2002 issue of Developmental Cell, Bruinsma et al. report that the CDF
      1 cation diffusion facilitator protein is required for efficient Ras-mediated
      signaling in C. elegans. CDF-1 reduces intracellular Zn(2+) levels, indicating an
      inhibitory effect of Zn(2+) on the Ras pathway.

PMID- 12049730
TI  - DNA binding and bending to initiate packaging of phage lambda DNA.
AB  - Physical and genetic studies verify that the DNA binding domain of protein gpNu1
      (which initiates packaging of phage lambda DNA) is a winged helix-turn-helix (w
      HTH) and that gpNu1 dimers bind sites that are brought close through DNA bending.

PMID- 12049731
TI  - The anaphase-promoting complex: proteolysis in mitosis and beyond.
AB  - Key events in mitosis such as sister chromatid separation and subsequent
      inactivation of cyclin-dependent kinase 1 are regulated by ubiquitin-dependent
      proteolysis. These events are mediated by the anaphase-promoting complex (APC), a
      cell cycle-regulated ubiquitin ligase that assembles multiubiquitin chains on
      regulatory proteins such as securin and cyclins and thereby targets them for
      destruction by the 26S proteasome.

PMID- 12049732
TI  - The PHD domain of MEKK1 acts as an E3 ubiquitin ligase and mediates
      ubiquitination and degradation of ERK1/2.
AB  - ERK1/2 MAP kinases are important regulators in cellular signaling, whose activity
      is normally reversibly regulated by threonine-tyrosine phosphorylation. In
      contrast, we have found that stress-induced ERK1/2 activity is downregulated by
      ubiquitin/proteasome-mediated degradation of ERK1/2. The PHD domain of MEKK1, a
      RING finger-like structure, exhibited E3 ubiquitin ligase activity toward ERK2 in
      vitro and in vivo. Moreover, both MEKK1 kinase activity and the docking motif on
      ERK1/2 were involved in ERK1/2 ubiquitination. Significantly, cells expressing
      ERK2 with the docking motif mutation were resistant to sorbitol-induced
      apoptosis. Therefore, MEKK1 functions not only as an upstream activator of the
      ERK and JNK through its kinase domain, but also as an E3 ligase through its PHD
      domain, providing a negative regulatory mechanism for decreasing ERK1/2 activity.

PMID- 12049733
TI  - Mathematical models of protein kinase signal transduction.
AB  - We have developed a mathematical theory that describes the regulation of
      signaling pathways as a function of a limited number of key parameters. Our
      analysis includes linear kinase-phosphatase cascades, as well as systems
      containing feedback interactions, crosstalk with other signaling pathways, and/or
      scaffolding and G proteins. We find that phosphatases have a more pronounced
      effect than kinases on the rate and duration of signaling, whereas signal
      amplitude is controlled primarily by kinases. The simplest model pathways allow
      amplified signaling only at the expense of slow signal propagation. More complex
      and realistic pathways can combine high amplification and signaling rates with
      maintenance of a stable off-state. Our models also explain how different agonists
      can evoke transient or sustained signaling of the same pathway and provide a
      rationale for signaling pathway design.

PMID- 12049734
TI  - Three-dimensional secretion signals in chaperone-effector complexes of bacterial
      pathogens.
AB  - The type III secretion system (TTSS) of Gram-negative bacterial pathogens
      delivers effector proteins required for virulence directly into the cytosol of
      host cells. Delivery of many effectors depends on association with specific
      cognate chaperones in the bacterial cytosol. The mechanism of chaperone action is
      not understood. Here we present biochemical and crystallographic results on the
      Yersinia SycE-YopE chaperone-effector complex that contradict previous models of
      chaperone function and demonstrate that chaperone action is isolated to only a
      small portion of the effector. This, together with evidence for stereochemical
      conservation between chaperone-effector complexes, which are otherwise unrelated
      in sequence, indicates that these complexes function as general, three
      dimensional TTSS secretion signals and may endow a temporal order to secretion.

PMID- 12049735
TI  - Insights into specific DNA recognition during the assembly of a viral genome
      packaging machine.
AB  - Terminase enzymes mediate genome "packaging" during the reproduction of DNA
      viruses. In lambda, the gpNu1 subunit guides site-specific assembly of terminase
      onto DNA. The structure of the dimeric DNA binding domain of gpNu1 was solved
      using nuclear magnetic resonance spectroscopy. Its fold contains a unique winged
      helix-turn-helix (wHTH) motif within a novel scaffold. Surprisingly, a predicted
      P loop ATP binding motif is in fact the wing of the DNA binding motif. Structural
      and genetic analysis has identified determinants of DNA recognition specificity
      within the wHTH motif and the DNA recognition sequence. The structure reveals an
      unexpected DNA binding mode and provides a mechanistic basis for the concerted
      action of gpNu1 and Escherichia coli integration host factor during assembly of
      the packaging machinery.

PMID- 12049736
TI  - Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2)
      activation and is involved in resistance to taxol-induced apoptosis.
AB  - ErbB2 overexpression confers resistance to taxol-induced apoptosis by inhibiting
      p34(Cdc2) activation. One mechanism is via ErbB2-mediated upregulation of
      p21(Cip1), which inhibits Cdc2. Here, we report that the inhibitory
      phosphorylation on Cdc2 tyrosine (Y)15 (Cdc2-Y15-p) is elevated in ErbB2
      overexpressing breast cancer cells and primary tumors. ErbB2 binds to and
      colocalizes with cyclin B-Cdc2 complexes and phosphorylates Cdc2-Y15. The ErbB2
      kinase domain is sufficient to directly phosphorylate Cdc2-Y15. Increased Cdc2
      Y15-p in ErbB2-overexpressing cells corresponds with delayed M phase entry.
      Expressing a nonphosphorylatable mutant of Cdc2 renders cells more sensitive to
      taxol-induced apoptosis. Thus, ErbB2 membrane RTK can confer resistance to taxol
      induced apoptosis by directly phosphorylating Cdc2.

PMID- 12049737
TI  - Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery.
AB  - A mechanism that triggers neuronal apoptosis has been characterized. We report
      that the cell cycle-regulated protein kinase Cdc2 is expressed in postmitotic
      granule neurons of the developing rat cerebellum and that Cdc2 mediates apoptosis
      of cerebellar granule neurons upon the suppression of neuronal activity. Cdc2
      catalyzes the phosphorylation of the BH3-only protein BAD at a distinct site,
      serine 128, and thereby induces BAD-mediated apoptosis in primary neurons by
      opposing growth factor inhibition of the apoptotic effect of BAD. The
      phosphorylation of BAD serine 128 inhibits the interaction of growth factor
      induced serine 136-phosphorylated BAD with 14-3-3 proteins. Our results suggest
      that a critical component of the cell cycle couples an apoptotic signal to the
      cell death machinery via a phosphorylation-dependent mechanism that may generally
      modulate protein-protein interactions.

PMID- 12049738
TI  - E2F1 and c-Myc potentiate apoptosis through inhibition of NF-kappaB activity that
      facilitates MnSOD-mediated ROS elimination.
AB  - Overexpression of c-Myc or E2F1 sensitizes host cells to various types of
      apoptosis. Here, we found that overexpressed c-Myc or E2F1 induces accumulation
      of reactive oxygen species (ROS) and thereby enhances serum-deprived apoptosis in
      NIH3T3 and Saos-2. During serum deprivation, MnSOD mRNA was induced by NF-kappaB
      in mock-transfected NIH3T3, while this induction was inhibited in NIH3T3
      overexpressing c-Myc or E2F1. In these clones, E2F1 inhibited NF-kappaB activity
      by binding to its subunit p65 in competition with a heterodimeric partner p50. In
      addition to overexpressed E2F1, endogenous E2F1 released from Rb was also found
      to inhibit NF-kappaB activity in a cell cycle-dependent manner by using E2F1(+/+)
      and E2F1(-/-) murine embryonic fibroblasts. These results indicate that E2F1
      promotes apoptosis by inhibiting NF-kappaB activity.

PMID- 12049739
TI  - c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53
      function: a mechanism for oncogene-induced genetic instability.
AB  - Oncogene overexpression activates p53 by a mechanism posited to involve
      uncharacterized hyperproliferative signals. We determined whether such signals
      produce metabolic perturbations that generate DNA damage, a known p53 inducer.
      Biochemical, cytological, cell cycle, and global gene expression analyses
      revealed that brief c-Myc activation can induce DNA damage prior to S phase in
      normal human fibroblasts. Damage correlated with induction of reactive oxygen
      species (ROS) without induction of apoptosis. Deregulated c-Myc partially
      disabled the p53-mediated DNA damage response, enabling cells with damaged
      genomes to enter the cycle, resulting in poor clonogenic survival. An antioxidant
      reduced ROS, decreased DNA damage and p53 activation, and improved survival. We
      propose that oncogene activation can induce DNA damage and override damage
      controls, thereby accelerating tumor progression via genetic instability.

PMID- 12049740
TI  - Structural and functional versatility of the FHA domain in DNA-damage signaling
      by the tumor suppressor kinase Chk2.
AB  - The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular
      responses to DNA damage. Identification of two pro-oncogenic mutations within the
      Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint
      activation. The X-ray structure of the Chk2 FHA domain in complex with an in
      vitro selected phosphopeptide motif reveals the determinants of binding
      specificity and shows that both mutations are remote from the peptide binding
      site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2
      phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1
      through either or both of two structurally distinct mechanisms. Although phospho
      dependent binding is important for Chk2 activity, previously uncharacterized
      phospho-independent FHA domain interactions appear to be the primary target of
      oncogenic lesions.

PMID- 12049741
TI  - Rad9 phosphorylation sites couple Rad53 to the Saccharomyces cerevisiae DNA
      damage checkpoint.
AB  - Rad9 is required for the MEC1/TEL1-dependent activation of Saccharomyces
      cerevisiae DNA damage checkpoint pathways mediated by Rad53 and Chk1. DNA damage
      induces Rad9 phosphorylation, and Rad53 specifically associates with
      phosphorylated Rad9. We report here that multiple Mec1/Tel1 consensus [S/T]Q
      sites within Rad9 are phosphorylated in response to DNA damage. These Rad9
      phosphorylation sites are selectively required for activation of the Rad53 branch
      of the checkpoint pathway. Consistent with the in vivo function in recruiting
      Rad53, Rad9 phosphopeptides are bound by Rad53 forkhead-associated (FHA) domains
      in vitro. These data suggest that functionally independent domains within Rad9
      regulate Rad53 and Chk1, and support the model that FHA domain-mediated
      recognition of Rad9 phosphopeptides couples Rad53 to the DNA damage checkpoint
      pathway.

PMID- 12049742
TI  - The yeast CDK inhibitor Sic1 prevents genomic instability by promoting
      replication origin licensing in late G(1).
AB  - G(1) cell cycle regulators are often mutated in cancer, but how this causes
      genomic instability is unclear. Here we show that yeast lacking the CDK inhibitor
      Sic1 initiate DNA replication from fewer origins, have an extended S phase, and
      inefficiently separate sister chromatids during anaphase. This leads to double
      strand breaks (DSBs) in a fraction of sic1 cells as evidenced by the accumulation
      of Ddc1 foci and a 575-fold increase in gross chromosomal rearrangements. Both S
      and M phase defects are rescued by delaying S-CDK activation, indicating that
      Sic1 promotes origin licensing in late G(1) by preventing the untimely activation
      of CDKs. We propose that precocious CDK activation causes genomic instability by
      altering the dynamics of S phase, which then hinders normal chromosome
      segregation.

PMID- 12049743
TI  - Direct observation of single MuB polymers: evidence for a DNA-dependent
      conformational change for generating an active target complex.
AB  - MuB, an ATP-dependent DNA binding protein, is critical for selection of target
      sites on the host chromosome during Mu transposition. We have developed a system
      for observing the behavior of single MuB polymers bound to an immobilized
      molecule of DNA. We show that the individual polymers display a broad
      distribution of disassembly rates and exhibit regional variations in DNA binding.
      Additionally, ATP hydrolysis was obligatorily coupled to dissociation of MuB
      subunits from the DNA during polymer disassembly. We propose a model in which the
      formation of an active target complex is mediated by a conformational change
      within the MuB polymer that is influenced by the sequence of the DNA.

PMID- 12049744
TI  - HIRA is critical for a nucleosome assembly pathway independent of DNA synthesis.
AB  - The mammalian HIRA gene encodes a histone-interacting protein whose homolog in
      Xenopus laevis is characterized here. In vitro, recombinant Xenopus HIRA bound
      purified core histones and promoted their deposition onto plasmid DNA. The
      Xenopus HIRA protein, tightly associated with nuclear structures in somatic
      cells, was found in a soluble maternal pool in early embryos. Xenopus egg
      extracts, known for their chromatin assembly efficiency, were specifically
      immunodepleted for HIRA. These depleted extracts were severely impaired in their
      ability to assemble nucleosomes on nonreplicated DNA, although nucleosome
      formation associated with DNA synthesis remained efficient. Furthermore, this
      defect was largely corrected by reintroduction of HIRA along with (H3-H4)(2)
      tetramers. We thus delineate a nucleosome assembly pathway that depends on HIRA.

PMID- 12049745
TI  - Functional interaction of yeast pre-mRNA 3' end processing factors with RNA
      polymerase II.
AB  - The RNA polymerase II CTD is essential for 3' end cleavage of metazoan pre-mRNAs
      and binds 3' end processing factors in vitro. We show genetic and biochemical
      interactions between the CTD and the Pcf11 subunit of the yeast
      cleavage/polyadenylation factor, CFIA. In vitro binding to Pcf11 required
      phosphorylation of the CTD on Ser2 in the YSPTSPS heptad repeats. Deletion of the
      yeast CTD reduced the efficiency of cleavage at poly(A) sites, and the length of
      poly(A) tails suggesting that it helps couple 3' end formation with
      transcription. Consistent with this model, the 3' end processing factors CFIA,
      CFIB, and PFI were recruited to genes progressively, starting at the 5' end, in a
      process that required ongoing transcription.

PMID- 12049746
TI  - Aberrant nuclear trafficking of La protein leads to disordered processing of
      associated precursor tRNAs.
AB  - Eukaryotic precursor tRNAs undergo extensive processing prior to nuclear export.
      The first of multiple factors to interact with pre-tRNAs and other nascent
      transcripts is the La protein. Using suppressor and wild-type tRNAs, we
      demonstrate that the normal distribution of cellular end-processed and spliced
      tRNA species is disordered by La proteins that lack a conserved nuclear retention
      element. Fission yeast or human La mutants that lack this element enter nuclei
      and stabilize nascent pre-tRNA but are aberrantly exported and fail to support
      normal tRNA processing. Instead, anomalous 5' and 3' end-containing, spliced
      tRNAs accumulate, complexed with the mutant La protein. Thus, appropriate nuclear
      trafficking by La affects the normal order of pre-tRNA processing.

PMID- 12049747
TI  - Accurate translocation of mRNA by the ribosome requires a peptidyl group or its
      analog on the tRNA moving into the 30S P site.
AB  - The ribosome must accurately translocate mRNA to maintain the reading frame.
      Here, we monitor the position of mRNA within the ribosome before and after EF-G
      catalyzed translocation near the initiation site. When a deacylated tRNA that is
      translocated to the 30S P site recognizes other nearby codons, movement of tRNA
      and mRNA often becomes uncoupled. Instead of moving in the 5' direction by 3
      nucleotides, the mRNA slips backward, repositioning the tRNA on an out-of-frame
      codon more optimally spaced from the Shine-Dalgarno sequence. In contrast, when
      peptidyl-tRNA or its analog (N-acetyl-aminoacyl-tRNA) is translocated in the same
      context, translocation of mRNA is highly accurate. If aminoacyl-tRNA is
      translocated, an intermediate level of translocational accuracy is observed.
      Thus, translocational accuracy depends on the acylation state of the tRNA
      entering the 30S P site.

PMID- 12049748
TI  - Protein interaction verification and functional annotation by integrated analysis
      of genome-scale data.
AB  - Assays capable of determining the properties of thousands of genes in parallel
      present challenges with regard to accurate data processing and functional
      annotation. Collections of microarray expression data are applied here to assess
      the quality of different high-throughput protein interaction data sets.
      Significant differences are found. Confidence in 973 out of 5342 putative two
      hybrid interactions from S. cerevisiae is increased. Besides verification,
      integration of expression and interaction data is employed to provide functional
      annotation for over 300 previously uncharacterized genes. The robustness of these
      approaches is demonstrated by experiments that test the in silico predictions
      made. This study shows how integration improves the utility of different types of
      functional genomic data and how well this contributes to functional annotation.

PMID- 12049749
TI  - A catalytically active group II intron domain 5 can function in the U12-dependent
      spliceosome.
AB  - Both spliceosomal and self-splicing group II introns require the function of
      similar small, metal binding RNA stem-loop elements located in U6 or U6atac
      snRNAs of the spliceosome or domain 5 (D5) of group II introns. Here we report
      that two different D5 elements can functionally replace the U6atac snRNA stem
      loop in an in vivo splicing assay. For efficient function in vivo, a single base
      pair from the upper helical section of the D5 sequence had to be removed.
      Introducing the equivalent base pair deletion into the D5 element of a group II
      intron reduced but did not eliminate self-splicing activity. Our results
      strengthen the case that these RNA elements play similar roles in the catalytic
      centers of both the spliceosome and a self-splicing ribozyme.

PMID- 12049750
TI  - Impedance analysis of ion transport through gramicidin channels in supported
      lipid bilayers.
AB  - Selectivity between monovalent cations and its sequence of conductivity in lipid
      bilayers doped with the antibiotic Gramicidin D (GD) were examined using EIS.
      Experiments were performed using lipid bilayers obtained from a lipid mixture of
      phosphatidylcholine and dimethyldioctadecylammonium chloride (DODAC). Lipid
      bilayers were supported on gold surfaces modified with a mercapto-carboxylic
      acid. The bilayers were formed by chemisorption of this last species to form the
      first monolayer on gold and subsequent fusion of unilamellar vesicles to form an
      external bilayer attached by electrostatic interactions. A mathematical
      expression for the impedance of the membrane processes was derived. Some
      predictions of the presented model were checked after fitting the experimental
      results in various electrolyte compositions.

PMID- 12049751
TI  - Effects of 60 Hz electromagnetic field exposure on APP695 transcription levels in
      differentiating human neuroblastoma cells.
AB  - Epidemiological studies have suggested that workers with primary occupation that
      are likely to have resulted in the medium-to-high extremely low frequency (ELF)
      electromagnetic field (EMF) exposure are at increased risk of Alzheimer's disease
      (AD) pathogenesis. As a first step in investigating the possibility of an
      association between the ELF-EMF exposure and AD at the cellular level, we have
      used the differentiating IMR-32 neuroblastoma cells. In double-blind experiments,
      IMR-32 cells were exposed to the magnetic field intensities of 50, 100, and 200
      microT at a frequency of 60 Hz for a period of 4 h at the three ages of
      differentiation (2, 10, and 16 days after incubation in differentiation medium).
      We used a custom-made Helmholtz coil setup driven by a 60-Hz sinusoidal signal
      from a function generator and an in-house built power amplifier. Total RNA
      extracted from the exposed cells was separated by the agarose gel electrophoresis
      and transferred to a nylon membrane for the northern hybridization. Digoxygenin
      labeled APP695 RNA probes were used to detect changes in the APP695 mRNA levels
      in response to the ELF-EMF exposure. The results reported herein provided no
      support for any relationship between the APP695 gene transcription and IMR-32
      differentiation age, as well as the magnetic field exposure. This study
      constitutes the first step towards investigating the possibility of an
      association between the ELF-EMF exposure and AD manifestations at the cellular
      level.

PMID- 12049752
TI  - Effect of metal ion exchange on the photocurrent response from bacteriorhodopsin
      on tin oxide electrodes.
AB  - The transient photocurrent response from bacteriorhodopsin (bR) on tin oxide
      electrodes was strongly influenced by metal ions bound to bR molecules. The
      photocurrent polarity reversal pH, which corresponded to the pH value for the
      reversal of the proton release/uptake sequence in the bR photocycle, of cation
      substituted purple membrane (PM) was shifted to lower pH with the increase in the
      cation affinities to carboxyl groups and a close correlation was noted between
      the two values. This suggests that the metal ion present in the extracellular
      region of a bR molecule modulates the pK(a) of proton release groups of bR by
      stabilizing the ionized state of the proton-releasing glutamic acids. The
      behavior of photocurrents at light-off in alkaline media, reflecting the proton
      uptake by bR, was unchanged by binding monovalent (Na(+) and K(+)) or divalent
      cations (Mg(2+) and Ca(2+)), but was drastically changed by binding La(3+) ions.
      This can be explained by invoking a substantial slowing of the proton uptake
      process in the presence of La(3+).

PMID- 12049753
TI  - On the formation kinetics of two-dimensional cytidine films.
AB  - The kinetics of phase transitions of cytidine adsorbed on mercury are studied by
      chronoamperometry and capacitance measurements. Cytidine forms highly ordered two
      dimensional adlayers in a broad range of pH. In acid solvent, only one kind of
      condensed layer is formed. In the alkaline solution, cytidine forms two different
      two-dimensional (2D) adlayers. The minimum capacitance value in adlayer II at pH
      5 is 7.0 microF cm(-2) and, at pH 8.3, it is 5.1 microF cm(-2); in adlayer III,
      the minimum capacitance is 10.6 microF cm(-2). The formation of a physisorbed
      film of cytidine molecules adsorbed at the mercury surface proceeds by complex
      mechanisms. From j-t transients, it can be seen that the phase transformations
      from dilute adlayer Ia to condensed physisorbed film II is accompanied by the
      reorientation of cytidine molecules at the mercury surface (inverted current
      transient). The interfacial transformations of the cytidine film yield a
      sigmoidal C-t transient. This experimentally measured C-t transient were analysed
      by Avrami theorem. The rate of the transformations from dilute adlayer Ia to
      condensed film II of cytidine at pH 5 depends strongly on temperature but is only
      slightly affected by temperature at pH 8.3. The effect of pH and ionic
      composition of the supporting electrolyte on the rate of transformation of
      cytidine films was studied as well.

PMID- 12049754
TI  - Highly sensitive sensors based on the immobilization of tyrosinase in chitosan.
AB  - A novel tyrosinase biosensor has been developed for a subpicomolar detection of
      phenols, which is based on the immobilization of tyrosinase in a positively
      charged chitosan film on a glassy carbon electrode. It was found that chitosan
      cross-linked with (3-aminooryloxypropyl) dimethoxymethylsilane is beneficial for
      the immobilization of tyrosinase. The large microscopic surface area and porous
      morphology of chitosan matrix lead to high enzyme loading, and the enzyme
      entrapped in this matrix can retain its bioactivity and the positively charged
      surface of chitosan can also display a good anti-interference ability to the
      substances with positive charge. Hence, the resulting sensor offers a high
      sensitivity (150 nA.nM(-1)) for the monitoring of phenols, and the detection
      limit is as low as 5.0 x 10(-11) M. Its response time is less than 2 s reaching
      95% of the steady-state value. It may retain 75% of the activity for at least 70
      days.

PMID- 12049755
TI  - Impedance measurements of self-assembled lipid bilayer membranes on the tip of an
      electrode.
AB  - Supported lipid membranes were self-assembled on the tip of a freshly cleaved
      silver wire, in the presence of an appropriate polarization voltage, to
      facilitate, during the membrane formation, the organization of the lipids into an
      ordered structure. Radiowave impedance spectroscopy measurements have been
      carried out to provide information on the relaxation properties of the system. We
      have measured the conductometric and dielectric properties of bilayers built up
      of different lipids [dipalmitoylphosphatidic acid (DPPA), 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC), linoleic acid (LIN)] in a wide frequency range
      (from 10(3) to 10(6) Hz) and in electrolyte solutions of different ionic
      strengths, in the presence of uni-univalent (KCl) and di-univalent (CaCl(2),
      MgCl(2), ZnCl(2)) electrolytes. This made it possible to measure the influence of
      different cations and different lipid compositions on the membrane properties. In
      particular, we have found a different capacitive behaviour of the supported lipid
      bilayer membrane (s-BLM) structure in the presence of different counterions in
      the electrolyte solution. This peculiarity offers the opportunity for the
      preparation of a variety of biosensors with diverse applications in membrane
      biophysics, biochemistry and biotechnology.

PMID- 12049757
TI  - Theoretical analysis of localized heating in human skin subjected to high voltage
      pulses.
AB  - Electroporation, the increase in the permeability of bilayer lipid membranes by
      the application of high voltage pulses, has the potential to serve as a mechanism
      for transdermal drug delivery. However, the associated current flow through the
      skin will increase the skin temperature and might affect nearby epidermal cells,
      lipid structure or even transported therapeutic molecules. Here, thermal
      conduction and thermal convection models are used to provide upper and lower
      bounds on the local temperature rise, as well as the thermal damage, during
      electroporation from exponential voltage pulses (70 V maximum) with a 1 ms and a
      10 ms pulse time constant. The peak temperature rise predicted by the conduction
      model ranges from 19 degrees C for a 1 ms time constant pulse to 70 degrees C for
      the 10 ms time constant pulse. The convection (mass transport) model predicts a
      18 degrees C peak rise for 1 ms time constant pulses and a 51 degrees C peak rise
      for a 10 ms time constant pulse. The convection model compares more favorably
      with previous experimental studies and companion observations of the local
      temperature rise during electroporation. Therefore, it is expected that skin
      electroporation can be employed at a level which is able to transport molecules
      transdermally without causing significant thermal damage to the tissue.

PMID- 12049756
TI  - Plant bioelectrochemistry: effects of CCCP on electrical signaling in soybean.
AB  - Carbonyl cyanide 3-chlorophenylhydrazone (CCCP) induces fast action potentials
      and decreases the variation potential in soybean plants. The propagation speed of
      the action potentials in a soybean plant produced by CCCP reaches up to 25 m/s.
      The duration of single action potentials after treatment by CCCP is 0.6 ms. The
      addition of CCCP to soil reduces variation or streaming potential to zero. The
      mechanism by which CCCP decreases plant maturation most likely includes
      depolarization of the plasma membrane, retardation of photosynthetic water
      oxidation, and respiratory electron transfer.

PMID- 12049758
TI  - Kinetics of the temperature rise within human stratum corneum during
      electroporation and pulsed high-voltage iontophoresis.
AB  - Electroporation is believed to be a nonthermal phenomenon at the membrane level.
      However, the effects of associated processes, such as Joule heating, should be
      considered. Because electroporation of skin, specifically the stratum corneum
      (SC), occurs at highly localized sites, the heating is expected to conform
      locally to the sites of electroporation. Significant localized heating was found
      to be strongly dependent on the voltage and duration of the high-voltage pulses.
      Specifically, a localized temperature rise was predicted theoretically and
      confirmed by experiments, with only a small rise (about 17 degrees C) for short,
      large pulses (1 ms, 100 V across the SC), but was increased (about 54 degrees C)
      for long, large pulses (300 ms, 60 V across the SC). The latter case appears to
      result in irreversible structural changes like vesicularization of the lipid
      lattice. These results support the hypothesis that electroporation occurs within
      the SC and that additional processes, such as localized heating, may be
      important.

PMID- 12049759
TI  - Charged cylindrical surfaces: effect of finite ion size.
AB  - A simple statistical mechanical approach is applied to calculate the profile of
      the density of the number of particles and the profile of the electrostatic
      potential of an electric double layer formed by a charged cylindrical surface in
      contact with electrolyte solution. The finite size of particles constituting the
      electrolyte solution is considered by including the excluded volume effect within
      the lattice statistics while the electrostatic interactions are considered by
      means of the mean electrostatic field. It is shown that the excluded volume
      effect decreases the density of the number of counterions and increases the
      electrostatic potential near the charged cylindrical surface. The effect is more
      pronounced for high area densities of charge of the charged surface and for
      larger counterions. Further, it is shown that the ratio between the density of
      the number of the counterions near the charged cylindrical surface and the
      density of the number of counterions far from the charged surface reaches a
      plateau at large linear charge densities for ions of finite size, while no
      plateau is reached for dimensionless ions. The effective thickness of the
      electric double layer in cylindrical geometry is introduced. It is shown that the
      effective thickness increases with increasing counterion size while its
      dependence on the area density of charge of the charged surface exhibits a
      minimum. The theoretical approach presented in this work can be used for
      description of the electrostatics of the thin cylindrical structures in
      biological systems such as DNA, protein macromolecules and charged micro and nano
      tubes.

PMID- 12049760
TI  - Calculation of dielectric spectra of suspensions of rod-shaped cells using
      boundary element method.
AB  - The boundary element method (BEM) has been applied to the calculation of
      dielectric spectra of suspensions of rod-shaped cells using two kinds of models:
      model-R consisting of a cylinder and two hemispheres and model-PU of prolate
      spheroid shape. Both models have an insulating shell phase of a uniform
      thickness. The calculations were compared with those using a conventional
      spheroidal model with a confocal shell (model-PC) and previous observations on
      rod-shaped yeast cells. The differences among the three models were not
      considerable and all the models succeeded in interpreting the observed data on
      yeast cells.

PMID- 12049761
TI  - LoMAPAM--Logical Model of Autowave Processes of Amoebic Movement.
AB  - This work describes a logical discrete model of the spatiotemporal dynamics of
      amoebic movement (Logical Model of Autowave Processes of Amoebic Movement
      (LoMAPAM)) based on finite automata (homogeneous structures) and specified for
      Physarum polycephalum. The basic system of passing rules for the information and
      regulation levels of the model, describing the contractile behavior of the
      ectoplasmic walls of P. polycephalum, enables a rhythmic generation of
      contractile waves and their propagation in the ectoplasmic wall due to the
      created structure of the LoMAPAM model. The finite automata corresponds to
      elementary square planar elements. This construction is alike homogeneous
      structures with the only exception is its finite. The planar element is assigned
      to the pair of integers (i,j). The state vector defined for every element (i,j)
      in discrete time t will have three components. Each of them will be written in
      one of the matrices B, C, or W. The information matrix B describes the state of
      the matter. The regulation matrix C, the local Ca(2+) concentration. The flow
      matrix W describes the local flow of endoplasm or ectoplasm. The passing rules
      for the state vector was written in the form of Boolean functions. Six actomyosin
      generators placed on a circle and three and five neighbouring ectoplasmatic
      generators on a line and a layer of endoplasm were analysed.

PMID- 12049762
TI  - Wing vein formation in Drosophila melanogaster: hairless is involved in the cross
      talk between Notch and EGF signaling pathways.
AB  - Wing vein development in Drosophila is controlled by different morphogenetic
      pathways, including Notch. Hairless (H) antagonizes Notch target gene activation
      by binding to the Notch signal transducer Suppressor of Hairless [Su(H)].
      Accordingly, overexpression of H phenocopies reduction of Notch activity.
      Deletion of the Su(H)-binding domain in H-C2 results in loss of H activity.
      However, overexpression of H-C2 induces formation of ectopic veins. In a screen
      for genetic modifiers of this phenotype, we have identified several genes
      involved in Notch and epidermal growth factor (EGF) signaling. Most notably
      veinlet, an activator of EGF signaling, acts downstream of H-C2. H-C2 positively
      regulates veinlet maybe through inhibition of inter-vein determinants in
      agreement with a model, whereby Notch and EGF signaling pathways cross-regulate
      vein pre-patterning.

PMID- 12049763
TI  - Cadherin-17 is required to maintain pronephric duct integrity during zebrafish
      development.
AB  - We have isolated a zebrafish cadherin that is orthologous to human LI-cadherin
      (CDH17). Zebrafish cdh17 is expressed exclusively in the pronephric ducts during
      embryogenesis, and in the mesonephros during larval development and adulthood.
      Like its mammalian ortholog, cdh17 is also expressed in liver and intestine in
      adult zebrafish. We show that cdh17-positive mesodermal cells do not contribute
      to the hematopoietic system. Consistent with a cell adhesion role for Cdh17,
      depletion of Cdh17 function using antisense morpholino oligonucleotides
      compromised cell cohesion during pronephric duct formation. Our results indicate
      that Cdh17 is necessary for maintaining the integrity of the pronephric ducts
      during zebrafish embryogenesis. This finding contrasts with the role of mammalian
      CDH17, which does not appear to be involved in nephric development.

PMID- 12049764
TI  - Gcm1 expression defines three stages of chorio-allantoic interaction during
      placental development.
AB  - The formation of the labyrinth layer is a critical step of placental development.
      The transcription factor glial cells missing 1 (Gcm1) plays a pivotal role in
      labyrinth development, but the sequence of events controlling its expression has
      not been identified yet. Our studies presented herein show that Gcm1 expression
      occurs in three distinct phases during placental development, each specific to a
      particular stage of chorio-allantois interaction. In the first, the pre-fusion
      phase, Gcm1 mRNA is expressed in isolated clusters of chorionic cells, but not
      efficiently translated. Upon allantois-chorion fusion, the second phase, Gcm1
      expression is greatly induced in clusters of chorionic cells separated by non
      expressing cells and the Gcm1 mRNA is translated to protein. In the third phase,
      the labyrinth formation, cells expressing Gcm1 proliferate, involute in the
      chorionic plate and branched villi formation begins.

PMID- 12049765
TI  - An essential function of AP-1 heterodimers in Drosophila development.
AB  - Fos and Jun proteins homo- or heterodimerize to form functional AP-1
      transcription factors. Drosophila mutants lacking either Jun or Fos display
      indistinguishable dorsal open phenotypes, indicating an essential function of
      both Jun and Fos for embryonic dorsal closure. Here we present experiments to
      determine the basis for this dual requirement. By combining mutant alleles and
      transgenes expressing Fos and Jun variants with altered dimerization preferences,
      fly lines were generated in which only specifically defined dimer variants can
      form. Phenotypic analysis of these mutants reveals that homodimers of Fos or of
      Jun cannot replace the function of the heterodimeric complex. This defect is not
      explained by the lower stability of homodimers as compared to heterodimers,
      because 'pseudo-homodimers' which are as stable as native Jun-Fos heterodimers
      cannot substitute for their function. We conclude that Jun and Fos play
      complementary roles that are both required for signal transduction and gene
      activation during dorsal closure.

PMID- 12049766
TI  - Furin cleavage is not a requirement for Drosophila Notch function.
AB  - Notch (N) is a large transmembrane protein that acts as a receptor in an
      evolutionarily conserved intercellular signalling pathway. Because of this
      conservation, it has been assumed that biochemical events mediating N function
      are identical in all species. For instance, intracellular maturation by furin
      protease and subunit assembly leading to the formation of a heterodimeric cell
      surface N receptor are thought to be central to its function in both mammals and
      flies. However, in Drosophila the majority of N appears to be full-length. It has
      not been determined whether this full-length N protein is on the cell surface. We
      describe experiments which indicate that unlike mammalian N, the majority of
      Drosophila N on the cell surface is full-length and that in Drosophila, in vivo,
      furin cleavage is not required for biological activity. We further show that the
      behaviour of fly and mouse N can be interchanged simply by swapping the regions
      in which the mammalian furin-like cleavage site is located.

PMID- 12049767
TI  - E-cadherin is a survival factor for the lactating mouse mammary gland.
AB  - The Ca(++)-dependent cell adhesion molecule E-cadherin is expressed throughout
      mouse development and in adult tissues. Classical gene targeting has demonstrated
      that E-cadherin-deficient embryos die at the blastocyst stage. To study the
      involvement of E-cadherin in organogenesis, a conditional gene inactivation
      scheme was undertaken using the bacteriophage P1 recombinase Cre/loxP system.
      Mice with homozygous loxP sites in both alleles of the E-cadherin (Cdh1) gene
      were generated and these mice were crossed with transgenic mice with the Cre
      recombinase under the control of the hormone-inducible MMTV promoter. This
      resulted in deletion of the E-cadherin gene in the differentiating alveolar
      epithelial cells of the mammary gland. The mutant mammary gland developed
      normally up to 16-18 days of pregnancy but exhibited a dramatic phenotype around
      parturition. The production of milk proteins was so drastically reduced that
      adult mutant mothers could not suckle their offspring. Thus, the lack of E
      cadherin affected the terminal differentiation program of the lactating mammary
      gland. In concordance with this finding, the prolactin-dependent activation of
      the transcription factor Stat5a was initiated but not maintained in the mutant
      gland. Instead, without E-cadherin massive cell death was observed at parturition
      and the mutant mammary gland at this stage resembled that of the involuted gland
      normally seen after weaning. These results demonstrate an essential role for E
      cadherin in the function of differentiated alveolar epithelial cells. No tumors
      were detected in mutant glands lacking E-cadherin.

PMID- 12049768
TI  - Nipple connective tissue and its development: insights from the K14-PTHrP mouse.
AB  - Parathyroid hormone-related protein (PTHrP) regulates a wide variety of
      developmental processes. Keratin 14 (K14) promoter-mediated overexpression of
      PTHrP in the epidermis during development converts the entire murine ventral skin
      to hairless nipple-like skin. In this report, we characterize the morphology and
      processes that influence the development of nipple connective tissue. The
      connective tissue of the nipple displayed increased levels of proteoglycans, and
      collagen bundles with atypical morphology, as well as increased numbers of mast
      cells, capillaries, nerve fibers and dermal melanocytes. The unique
      characteristics of nipple connective tissue were not present until mice reach 3-4
      weeks of age. The adult male K14-PTHrP mouse has a less dramatic ventral skin
      phenotype, and does not manifest a nipple-like dermis. Ovariectomy or
      orchiedectomy prior to sexual maturity had no impact on the ventral skin of the
      male or female K14-PTHrP mice, but exposure to androgens in utero repressed many
      of the nipple-like characteristics in the ventral skin of the female K14-PTHrP
      mice.

PMID- 12049769
TI  - Repression through a distal TCF-3 binding site restricts Xenopus myf-5 expression
      in gastrula mesoderm.
AB  - The development of skeletal muscle in the vertebrate embryo is controlled by a
      transcriptional cascade that includes the four myogenic regulatory factors Myf-5,
      MyoD, Myogenin, and MRF4. The dynamic expression pattern of myf-5 during
      myogenesis is thought to be consistent with its role during early determination
      of the myogenic lineage. To study the factors and mechanisms, which regulate myf
      5 transcription in Xenopus, we isolated a genomic DNA clone containing 4858 bp of
      Xmyf-5 5' flanking region. Using a transgenic reporter assay, we show here that
      this genomic contig is sufficient to recapitulate the dynamic stage- and tissue
      specific expression pattern of Xmyf-5 from the gastrula to tail bud stages. For
      the primary induction of myf-5 transcription, we identify three main regulatory
      elements, which are responsible for (i) activation in dorsal mesoderm, (ii)
      activation in ventral mesoderm, and (iii) repression in midline mesoderm,
      respectively. Their combined activities define the two-winged expression domain
      of myf-5 in the preinvoluted mesoderm. Repression in midline mesoderm is mediated
      by a single TCF binding site located in the 5' end of the -4.8 kbp sequence,
      which binds XTcf-3 protein in vitro. Endogenous Wnt signaling in the lateral
      mesoderm is required to overcome the long-range repression through this distal
      TCF site, and to stimulate myf-5 transcription independently from it. The element
      for ventral mesoderm activation responds to Activin. Together, these results
      describe a regulatory mosaic of repression and activation, which defines the myf
      5 expression profile in the frog gastrula.

PMID- 12049770
TI  - Transrepression of AP-1 by nuclear receptors in Drosophila.
AB  - Mammalian cell culture studies have shown that several members of the nuclear
      receptor super family such as glucocorticoid receptor, retinoic acid receptor and
      thyroid hormone receptor can repress the activity of AP-1 proteins by a mechanism
      that does not require the nuclear receptor to bind to DNA directly, but that is
      otherwise poorly understood. Several aspects of nuclear receptor function are
      believed to rely on this inhibitory mechanism, which is referred to as
      transrepression. This study presents evidence that nuclear receptor-mediated
      transrepression of AP-1 occurs in Drosophila melanogaster. In two different
      developmental situations, embryonic dorsal closure and wing development, several
      nuclear receptors, including Seven up, Tailless, and Eagle antagonize AP-1. The
      inhibitory interactions with nuclear receptors are integrated with other modes of
      AP-1 regulation, such as mitogen-activated protein kinase signaling. A potential
      role of nuclear receptors in setting a threshold of AP-1 activity required for
      the manifestation of a cellular response is discussed.

PMID- 12049771
TI  - A naturally occurring alternative product of the mastermind locus that represses
      notch signalling.
AB  - The mastermind locus encodes a nuclear protein required in the Notch signalling
      pathway. In a screen for genes affecting wing pattern, we identified an EP
      element that directs expression of an alternatively spliced form of the
      mastermind transcript that we call mam[DN]. Unlike the conventional mam
      transcript, mam[DN] is spatially regulated in the developing embryonic nervous
      system and eye imaginal disc. mam[DN] corresponds to an endogenous transcript and
      encodes an alternate form of the Mam protein that dominantly interferes with
      activity of the conventional Mam protein. Mam[DN] blocks Notch signalling
      downstream from the activated form of Notch but cannot interfere with an
      activated form of Su(H), suggesting that Mam[DN] may interfere with the activity
      of a ternary complex involving Mam, Notch and Su(H).

PMID- 12049772
TI  - Lateral line, nervous system, and maternal expression of Frizzled 7a during
      zebrafish embryogenesis.
AB  - We have isolated and mapped a new wnt receptor frizzled family member, zebrafish
      frizzled 7a. Fz7a and a previously reported zebrafish fz7 (El-Messaoudi and
      Renucci, 2001) make an orthologous gene pair, however, they display distinct
      expression patterns. Fz7a shows strong maternal as well as zygotic expression.
      Fz7a transcript is enriched dorsally starting with the shield stage. At the end
      of gastrulation, Fz7a is abundantly expressed within anterior neuroectoderm and
      expressed more weakly within lateral mesoderm. Fz7a is detected during
      somitogenesis within the central nervous system, somatic and posterior lateral
      mesoderm. At 24hpf, fz7a is expressed in migrating lateral line primordium. At
      48hpf, fz7a is detected in the ear, pectoral fin bud, and within neuromasts,
      which had originated from the lateral line primordium. Radiation hybrid mapping
      using panel LN54 (Hukriede et al., 1999) places fz7a on linkage group 6, linked
      to the marker fi11h08 (distance 0.00cR, LOD score 14.1). To prove that fz7 and
      fz7a are indeed different genes we mapped fz7 as well using the same LN54 panel.
      Fz7 mapped to linkage group 9 with a LOD of 12.5, 27.31 cR from wnt 10a in
      between markers IBD2759 and fb50e04.

PMID- 12049773
TI  - cDNA cloning, sequence comparison, and developmental expression of Xenopus rac1.
AB  - The Rho family of small GTP-binding proteins are important signaling molecules
      that regulate the dynamics of the actin cytoskeleton and mediate changes in cell
      morphology and motility. Here, we describe the temporal and spatial patterns of
      expression of the Rho family member, rac, during the development of the
      amphibian, Xenopus laevis. We also present the deduced amino acid sequence of
      Xenopus rac (Xrac). At the amino acid level, Xrac is highly conserved relative to
      previously characterized rac homologs, and is nearly identical to human rac1.
      RNase protection assays and Western blot analysis indicate that Xrac mRNA and
      protein are present from fertilization through tailbud stages of development.
      Whole-mount in situ hybridizations show that Xrac transcripts are especially
      abundant in cells of the involuting marginal zone, and later, in the cranial
      neural crest, the developing central nervous system, and in the somites. The
      remarkable degree of evolutionary conservation observed in the Xrac primary
      structure together with its high level of expression in cells and structures
      critical to morphogenesis suggest a functionally important role for this Rho
      family member in early vertebrate development.

PMID- 12049774
TI  - XSPR-1 and XSPR-2, novel Sp1 related zinc finger containing genes, are
      dynamically expressed during Xenopus embryogenesis.
AB  - Proteins related to the human transcription factor Sp1 are characterized by the
      presence of a highly conserved zinc finger domain consisting of three C2H2 type
      zinc fingers. Here we describe two Xenopus laevis cDNAs, which encode novel Sp1
      related C2H2 type zinc finger transcription factors named XSPR-1 and XSPR-2.
      Structurally, XSPR-1 and XSPR-2 are closely related to the murine Sp5, which
      interacts genetically with Brachyury (Dev. Biol. 227 (2000) 358). XSPR-1 and XSPR
      2 are expressed in broad and dynamic patterns during early development. Starting
      at gastrulation, XSPR-1 transcripts are restricted to the non-involuting marginal
      zone, and, at later stages, to the neuroectoderm, forebrain, otic vesicles and
      the midbrain/hindbrain boundary. In contrast, XSPR-2 expression is found
      predominantly within the presumptive mesoderm during gastrulation. At tailbud and
      tadpole stages, XSPR-2 is expressed exclusively in the tip of the tail.

PMID- 12049775
TI  - Cardiac specific expression of Xenopus Popeye-1.
AB  - Popeye genes code for putative transmembrane proteins that are predominantly
      expressed in heart and skeletal muscle. Here we report on the isolation and
      expression of a previously unknown Xenopus member of this family, Xenopus Popeye
      1 (Xpop-1). Xpop-1 is 60-65% identical to other vertebrate Pop-1 genes at the
      protein level. Whole-mount in situ hybridization studies revealed a highly
      specific expression of Xpop-1 whose transcripts are restricted to the embryonic
      heart and become enriched in the forming ventricle. Interestingly, unlike other
      known vertebrate Popeye genes, Xpop-1 is exclusively expressed in cardiac tissue
      and absent from skeletal muscle.

PMID- 12049776
TI  - Developmental expression pattern of oncostatin M receptor beta in mice.
AB  - Oncostatin M (OSM), which is predominantly expressed in bone marrow, is a member
      of the interleukin-6 family of cytokines, and appears to play important roles in
      hematopoiesis and the development of the liver. Recently, specific beta subunit
      of OSM receptor (OSMRbeta) was isolated from LO cells originated from aorta-gonad
      mesonephros (AGM) region. In this study, we performed in situ hybridization to
      explore the expression pattern of OSMRbeta during murine embryogenesis, postnatal
      development, and in adult tissues. At 11.5 days postcoitum (dpc), the expression
      of OSMRbeta was first detected in aortic endothelial cells of the AGM region. At
      14.5dpc, its gene expression was clearly observed in the primordia of some
      organs, including liver, thymus, choroid plexus, and limb, and persisted into
      postnatal mice. After birth, its gene expression became detectable in the other
      organs, such as lymph node, bone, heart, kidney, small intestine, nasal cavity,
      and lung.

PMID- 12049777
TI  - Differential expression of two somatostatin genes during zebrafish embryonic
      development.
AB  - We have identified the cDNAs of two new zebrafish preprosomatostatins, PPSS1 and
      PPSS3, in addition to the previously cloned PPSS2 (Argenton et al., 1999). PPSS1
      is the orthologue of mammalian PPSSs, with a conserved C-terminal SS-14 sequence,
      PPSS2 is a divergent SS precursor and PPSS3 is a cortistatin-like prohormone.
      Using whole-mount in situ hybridisation, we have analysed the expression of PPSS1
      and PPSS2 in zebrafish embryos up to 5 days post fertilisation. PPSS1 was
      expressed in the developing pancreas and central nervous system (CNS), whereas
      PPSS2 expression was exclusively pancreatic. In the CNS, PPSS1 was detected in
      several areas, in particular in the vagal motor nucleus and in cells that pioneer
      the tract of the postoptic commissure. PPSS1 was also expressed transiently in
      the telencephalon and spinal motor neurons. In all areas but the telencephalon
      PPSS1 was coexpressed with islet-1.

PMID- 12049778
TI  - Expression of cytosolic acetyl-CoA synthetase gene is developmentally regulated.
AB  - Acetyl-CoA synthetase (AceCS) provides acetyl-CoA for different physiological
      processes, such as fatty acid and cholesterol synthesis, as well as the citric
      acid cycle. We show here that the cytosolic isoform of this enzyme, AceCS1, is
      expressed during mouse development. In the embryonic stage E9.5 AceCS1
      transcripts localize in the cephalic region. At E10.5 the cephalic expression
      intensifies and transcripts appear also in the spinal cord and in the dorsal root
      ganglions. During organogenesis AceCS1 is expressed in the liver from E11.5. The
      AceCS1 gene is expressed also in the testes from E12.5 onwards and expression
      localizes in the interstitial Leydig cells. In the ovaries, expression is
      transient and AceCS1 transcripts are detected from E13.5 to E15.5 in the ovarian
      interstitial component. In the kidneys AceCS1 transcripts appear in a subset of
      the renal tubules at E16.5 and remains in these structures in newborns. Hence,
      expression of AceCS1 is developmentally regulated suggesting a role for AceCS1
      during embryogenesis.

PMID- 12049779
TI  - The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle
      but not in the heart.
AB  - In birds and mammals three isoforms of troponin I (TnI) exist; a slow (TnIs), a
      fast (TnIf) and a cardiac (TnIc). Although each of these isoforms is expressed in
      the adult forms of these organisms in a muscle fiber-type-specific manner, the
      gene encoding TnIs is also expressed within the developing heart of these
      vertebrates. Herein, our results demonstrate that the developing heart of Xenopus
      laevis, unlike its counterpart in birds and mammals, does not express the gene
      encoding the TnIs isoform and that the expression of this gene, as well as the
      one encoding the Xenopus TnIf isoform, is restricted to skeletal muscle.

PMID- 12049780
TI  - Expression pattern of cLhx2b, cZic1 and cZic3 in the developing chick
      diencephalon.
AB  - The diencephalon is the caudal part of the developing forebrain that gives rise
      to the epithalamus, thalamus, hypothalamus and retina. The mature diencephalon is
      functionally and anatomically parceled into well-defined nuclei. In an effort to
      understand how this region of the brain develops we examined the expression of
      several transcription factors during development. We find that the LIM
      homeodomain transcription factor, cLhx2b, and the zinc finger transcription
      factors, cZic1 and cZic3, are predominantly expressed in partially overlapping
      domains of the chick dorsal diencephalon. Interestingly, a correlation exists
      between their expression in neuroepithelial progenitor cells at early stages and
      in the differentiated nuclei at progressively more advanced stages of
      development.

PMID- 12049781
TI  - Arginase expression in mouse embryonic development.
AB  - We are using the model of the developing mouse embryo to elucidate the pattern of
      arginase expression in mammalian cells in normal animals and in arginase I (AI)
      deficiency during development by digoxigenin-labeled RNA in situ hybridization.
      Our goal is to understand the regulation of these isozymes, with the expectation
      that this knowledge will help patients suffering from AI deficiency. We found
      that AI mRNA was widely and strongly expressed in the normal developing mouse
      embryo; in contrast, a relatively strong AII mRNA signal was found only in the
      intestine. In the AI knockout mouse embryo, no AII overexpression was found.
      These results indicated that arginases are needed in mouse embryonic development
      and AI is the principal form required. The strong AI expression in the peripheral
      nervous system suggests that the pathogenesis of the neurological retardation in
      AI deficiency may be conditioned by AI deficiency in the nervous system during
      embryonic development.

PMID- 12049782
TI  - Allele-specific expression of imprinted genes in mouse migratory primordial germ
      cells.
AB  - In somatic cells, imprinted genes are expressed monoallelically according to
      parent-of-origin. In contrast, in 11.5 days post-coitum primordial germ cells
      (PGCs), and later stage germ cells, these same genes are expressed biallelically,
      suggesting that imprints inherited from the gametes are largely erased by this
      stage. To determine when in germ cell development this biallelic expression
      phenomenon commences, we isolated migrating PGCs by flow cytometry and determined
      the allele-specific expression of four imprinted genes - Snrpn, Igf2, H19 and
      Igf2r. The first three genes were expressed monoallelically, while the latter
      gene was expressed biallelically. These results show that inherited imprints
      regulating monoallelic expression are largely intact in migrating PGCs.

PMID- 12049783
TI  - SM22beta encodes a lineage-restricted cytoskeletal protein with a unique
      developmentally regulated pattern of expression.
AB  - Cytoskeletal proteins play important roles in regulating cellular morphology,
      cytokinesis and intracellular signaling. In this report, we describe a
      developmentally regulated gene encoding a novel cell lineage-restricted
      cytoskeletal protein, designated SM22beta. SM22beta shares high-grade sequence
      identity with the smooth muscle cell (SMC)-specific protein, SM22alpha, the
      neuron-specific protein, NP25, and the Drosophila melanogaster flight muscle
      specific protein, mp20. The mouse SM22beta cDNA encodes a 199-amino acid
      polypeptide that contains a single conserved calponin-like repeat domain. During
      mouse embryonic development, the SM22beta gene is expressed in a temporally and
      spatially regulated pattern in the tunica media of arteries and veins,
      endocardium and compact layer of the myocardium, bronchial epithelium and
      mesenchyme of the lung, gastrointestinal epithelium and cartilaginous primordia.
      During postnatal development, SM22beta is co-expressed with SM22alpha in arterial
      and venous SMCs. In addition, SM22beta is expressed at high levels in the
      bronchial epithelium and lung mesenchyme, gastrointestinal epithelial cells and
      in the cartilagenous and periosteal layer of bones. Three-dimensional
      deconvolution microscopic analyses of A7r5 SMCs revealed that SM22beta co
      localizes with SM22alpha to cytoskeletal actin filaments. Taken together, these
      data demonstrate that SM22beta is a novel actin-associated protein with a unique
      cell lineage-restricted pattern of expression.

PMID- 12049784
TI  - Developmental and cell type-specific expression of the zinc finger transcription
      factor Kruppel-like factor 4 (Klf4) in postnatal mouse testis.
AB  - The transcription factor Kruppel-like factor 4 (Klf4, formerly gut-enriched
      Kruppel-like factor, GKLF) is specifically expressed in postproliferative
      epithelial cells such as those of the gut and the epidermis. The importance of
      Klf4 in terminal differentiation of keratinocytes has been demonstrated by
      targeted gene ablation in mice. Klf4-deficient mice fail to establish the barrier
      function of the skin and die shortly after birth due to dehydration. Based on
      these findings as well as in vitro studies, Klf4 was characterized as a
      transcription factor essential for postproliferative differentiation of
      epithelial cells. However, the testicular Klf4 expression pattern is completely
      unknown. Here, we demonstrate that Klf4 is developmentally regulated during
      postnatal testicular development of the mouse. Furthermore, we show strong
      expression in the postmeiotic germ cells undergoing final differentiation into
      sperm cells and provide evidence that Klf4 is also expressed in the somatic
      Sertoli cells. These findings suggest that Klf4 might play an important role in
      testicular differentiation in mammals.

PMID- 12049786
TI  - The abdominal-B-like gene expression during larval development of Nereis virens
      (polychaeta).
AB  - We have studied the posterior Hox gene Nvi-Post1 expression in the early
      development of the polychaete Nereis virens. This is the first evidence of the
      posterior group Hox genes expression during the larval development of a
      Lophotrochozoan. The expression begins in the trochophore hyposphere at the
      prospective sites of larval parapodia. As the larva develops the expression
      weakens and finally becomes undetectable in the nectochaete stage and juvenile
      worm. The Nvi-Post1 expression appears to be important for larval, but not
      postlarval development.

PMID- 12049785
TI  - Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive
      set of endocrine cells in the embryonic pancreas.
AB  - The earliest endocrine cells in the developing pancreas make glucagon and are
      described as alpha cells. We show here that these cells express islet amyloid
      polypeptide and prohormone convertase 1/3 (PC1/3), proteins that are not
      expressed by mature alpha cells, but are found in beta cells. PC1/3 converts
      proglucagon to the functionally distinct hormones glucagon-like peptide (GLP)-1
      and GLP-2 rather than glucagon. Despite these differences, the early proglucagon
      positive cells express, as do mature alpha cells, the POU domain transcription
      factor Brn-4, and do not express the beta cell factor pdx-1. The early production
      of atypical peptide hormones by these cells suggests that they could play an
      important role locally or systemically in the development of the embryo.

PMID- 12049787
TI  - Expression of ADAMTS1 during murine development.
AB  - ADAMTS1/METH1 belongs to the ADAMTS (a disintegrin and metalloprotease with
      thrombospondin repeats) family of proteins that currently comprises 18 members.
      Targeted inactivation of the ADAMTS1 gene results in morphological defects in the
      kidney, adrenal gland, and adipose tissue in addition to growth retardation and
      infertility in females. To gain further insight on the biology of ADAMTS1, we
      examined its expression pattern in the developing mouse from embryonic day 10
      (E10) to E18. Expression analysis by RNase protection assays revealed detectable
      levels of ADAMTS1 transcripts in E10-E18 yolk sac, placenta, brain, heart, lung,
      limb bud, liver, spleen, and kidney, with much lower levels in the adult. Using
      in situ hybridization, we have localized ADAMTS1 transcripts predominantly to the
      epithelium of the developing lung, pancreas, kidney and to a subset of neurons in
      a temporally restricted manner. Expression was also detected in the tunica media
      of the aorta, pulmonary, and hepatic vessels.

PMID- 12049788
TI  - Talisia esculenta lectin and larval development of Callosobruchus maculatus and
      Zabrotes subfasciatus (Coleoptera: Bruchidae).
AB  - Bruchid larvae cause major losses in grain legume crops throughout the world.
      Some bruchid species, such as the cowpea weevil and the Mexican bean weevil, are
      pests that damage stored seeds. Plant lectins have been implicated as antibiosis
      factors against insects, particularly the cowpea weevil, Callosobruchus
      maculatus. Talisia esculenta lectin (TEL) was tested for anti-insect activity
      against C. maculatus and Zabrotes subfasciatus larvae. TEL produced ca. 90%
      mortality to these bruchids when incorporated in an artificial diet at a level of
      2% (w/w). The LD(50) and ED(50) for TEL was ca. 1% (w/w) for both insects. TEL
      was not digested by midgut preparations of C. maculatus and Z. subfasciatus. The
      transformation of the genes coding for this lectin could be useful in the
      development of insect resistance in important agricultural crops.

PMID- 12049789
TI  - First observation of solution structures of bradykinin-penta-O-galloyl-D
      glucopyranose complexes as determined by NMR and simulated annealing.
AB  - Polyphenols (tannins) are known for their high propensity to precipitate
      proteins. They bind most strongly to proteins with a high proline content.
      Understanding the mechanism of this association is of prime interest because this
      interaction might induce protein conformational changes that may modify their
      biological activity. To investigate the interaction, an NMR study was carried out
      on the binding of a representative polyphenol, penta-O-galloyl-D-glucopyranose,
      to a nonapeptide hormone, bradykinin (BDK), where proline accounts for 30% of
      residues. Series of 1D and 2D-NMR experiments were performed. For the first time,
      a three-dimensional structure of complexes was determined using 2D-NMR
      experiments and molecular modeling. These structure calculations are a potent
      tool to understand how the association arises. They clearly show that the
      interaction is a complex phenomenon where several parameters are involved. The
      PGG/BDK complexes are formed by multiple weak interactions between peptide side
      chains and galloyl rings. Proline and arginine are good anchoring points and the
      glycine gives a certain flexibility in the peptide backbone that allows the
      polyphenol to approach and interact. Therefore, it is not only the hydrophobic
      stackings between galloyl rings and proline and hydrogen bonding involving
      arginine and aromatic rings which are important. The residue sequence and the
      side chain steric bulk also intervene.

PMID- 12049790
TI  - Mechanisms of flavonoid repair reactions with amino acid radicals in models of
      biological systems: a pulse radiolysis study in micelles and human serum albumin.
AB  - Neutral tryptophan (*Trp) and tyrosine (TyrO(*)) radicals are repaired by certain
      flavonoids in buffer, in micelles and in human serum albumin (HSA) with
      corresponding formation of semioxidized flavonoid radicals. In deaerated buffer,
      *Trp but not TyrO(*) radicals react with catechin. In micelles, quercetin and
      rutin repair both *Trp and TyrO(*) radicals. In addition to amino acid
      reactivity, microenvironmental factors and nature of the flavonoids govern this
      repair. Electron transfer efficiencies from quercetin to negatively charged *Trp
      radicals are 100% in the micellar pseudophases of positively charged
      cetyltrimethylammonium bromide, (CTAB), and neutral Triton X100 (TX100), but 55%
      in negatively charged sodium dodecyl sulfate (SDS). In oxygen-saturated CTAB
      micelles, quercetin also reacts with the superoxide radical anion. When bound to
      domain IIA of HSA, quercetin repairs, by intra- or intermolecular encounter, less
      than 20% of oxidative damage to HSA. Quercetin can also repair freely circulating
      oxidized molecules with repair efficiencies falling to 7% for oxidized *Trp, Tyr
      and alpha-MSH and to less than 2% for urate radical. This limited effectiveness
      is attributed both to the inaccessibility of bound quercetin and rutin toward
      radicals of circulating molecules and to the diffusion-controlled recombination
      of these radicals.

PMID- 12049791
TI  - Prostaglandin E(2) production and induction of prostaglandin endoperoxide
      synthase-2 is inhibited in a murine macrophage-like cell line, RAW 264.7, by
      Mallotus japonicus phloroglucinol derivatives.
AB  - An aqueous acetone extract obtained from the pericarps of Mallotus japonicus
      (MJE) was observed to inhibit prostaglandin (PG) E(2) production in a
      lipopolysaccharide (LPS)-activated murine macrophage-like cell line, RAW 264.7.
      Six phloroglucinol derivatives isolated from MJE exhibited inhibitory activity
      against PGE(2) production. Among these phloroglucinol derivatives,
      isomallotochromanol showed the strongest inhibitory activity, with an IC(50) of
      1.0 microM. MJE and its phloroglucinol derivatives did not effect the enzyme
      activity of either prostaglandin endoperoxide synthase (PGHS)-1 or PGHS-2.
      However, induction of PGHS-2 in LPS-activated macrophages was inhibited by MJE
      and its phloroglucinol derivatives, whereas the level of PGHS-1 protein was not
      affected. Moreover, RT-PCR analysis showed that MJE and its phloroglucinol
      derivatives significantly suppressed PGHS-2 mRNA expression. Therefore, the
      observed inhibition of PGHS-2 induction by MJE and its phloroglucinol derivatives
      was likely due to a suppression of PGHS-2 mRNA expression. These results suggest
      that MJE and its phloroglucinol derivatives have the pharmacological ability to
      suppress PGE(2) production by activated macrophages.

PMID- 12049792
TI  - Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8
      dihydroneopterin.
AB  - 7,8-Dihydroneopterin and neopterin are secreted by human and primate macrophages
      after activation by interferon-gamma in a ratio of 2:1. 7,8-Dihydroneopterin is
      known to suppress radical-mediated processes, but it is also able in the presence
      of iron ions to generate superoxide radical anion and hydroxyl radicals from
      molecular oxygen. Effects of 7,8-dihydroneopterin were investigated on
      (met)myoglobin and (met)hemoglobin. Addition of 7,8-dihydroneopterin to heme
      proteins in air-saturated solution resulted in dose-dependent cleavage of the
      porphyrin moiety. The liberation of non-heme iron and carbon monoxide originating
      from the cleaved porphyrin was quantified. Both were generated at equimolar
      concentrations with a linear correlation coefficient of 0.9. Addition of ferrous
      iron significantly accelerated the pteridine-mediated cleaving of the porphyrin.
      However, the total yield of porphyrin cleaved was controlled by the pterin rather
      than by the ferrous ion concentration. 7,8-Dihydroneopterin is assumed to reduce
      the heme iron in intact protein molecules, thereby preparing the conditions for
      binding of oxygen and carbon monoxide as ligands. Beyond that, it is concluded
      that hydroxyl radicals might be generated via reduction of molecular oxygen to
      superoxide anion in the autoxidation process and dismutation to hydrogen peroxide
      and subsequent Fenton reaction.

PMID- 12049793
TI  - Regulation of glutamine metabolism during the development of Bombyx mori larvae.
AB  - Waste ammonia is re-assimilated into amino acids via the amide group of glutamine
      and the amino group of glutamate (i.e. through glutamine synthetase/glutamate
      synthase pathway) for silk synthesis in the silkworm, Bombyx mori, in the last
      larval stadium. Glutamine concentration in hemolymph gradually decreased with the
      progress of the fifth instar and it remained at very low levels during the
      spinning stage, then followed by a sharp increase at the larval-pupal ecdysis.
      The changes in glutamine synthetase (GS) activity in silkworm tissues were
      relatively small through the larval development, while the changes in glutamate
      synthase (GOGAT) activity, especially in the posterior silk glands, were more
      drastic. In addition, activities of GOGAT in the tissues were much higher than
      those of the other enzymes involved in glutamine utilization, suggesting that
      glutamine pool was regulated mainly by the changes in GOGAT activity. Western
      blot analysis indicated that the changes in GOGAT protein level correlated with
      the changes in GOGAT activity. Topical application of a juvenile hormone
      analogue, methoprene, induced an accumulation of glutamine in the hemolymph of
      the fifth instar larvae. The levels of GOGAT protein and activity in the tissues
      of the methoprene treated larvae were much lower than those of the control
      larvae, whereas the methoprene treatment had no effect on the levels of GS
      activity. In conclusion, GOGAT expression promoted by reduction of juvenile
      hormone titer is quite important for enhanced utilization of nitrogen for
      synthesis of silk protein during the last larval instar.

PMID- 12049794
TI  - The glucogenic response of a parasitized insect Manduca sexta L. is partially
      mediated by differential nutrient intake.
AB  - Induction of gluconeogenesis is accelerated in larvae of the insect Manduca sexta
      L. parasitized by Cotesia congregata (Say), maintaining the concentration of the
      blood sugar trehalose, an important nutrient for parasite development.
      Investigation has demonstrated that when host larvae are offered a choice of
      diets with varying levels of sucrose and casein, parasitized insects consume a
      different balance of these nutrients, principally due to a decrease in protein
      consumption. The result is metabolic homeostasis, with normal unparasitized and
      parasitized larvae exhibiting similar levels of gluconeogenesis and blood sugar
      level. In the present study, normal unparasitized and parasitized larvae were
      maintained on individual chemically defined diets having the balance of protein
      and carbohydrate consumed by each when offered a dietary choice. Total dietary
      nutrient, the sum of carbohydrate and protein, was provided at six levels,
      composed of three pairs of diets. Each diet pair consisting of diets having
      equivalent overall nutrient ratios of 2:1 and 1:1 casein/sucrose. Host growth and
      diet consumption were significantly affected by dietary nutrient level and the
      magnitude of these effects was influenced by parasitism. Due to the effects of
      dietary nutrient level on diet consumption, none of the unparasitized and
      parasitized larvae within any of the three diet pairs consumed protein and
      carbohydrate at the levels predicted by the earlier choice experiments. Among
      insects on all of the diets, however, two groups of unparasitized and parasitized
      larvae consumed the expected levels of protein and carbohydrate. In each case,
      gluconeogenesis, as measured by 13C nuclear magnetic resonance spectroscopy (NMR)
      analysis of pyruvate cycling and trehalose synthesis from [2-13C]pyruvate, was
      evident in unparasitized and parasitized insects, confirming the conclusions of
      the earlier experiments. Generally, all larvae that consumed less than
      approximately 250 mg of sucrose over the 3-day feeding period, were
      gluconeogenic, regardless of diet. Differential carbohydrate consumption,
      therefore, was an important factor in inducing gluconeogenesis in both
      unparasitized and parasitized insects. The selective 13C enrichment in trehalose
      displayed by non-gluconeogenic larvae on some diets demonstrated trehalose
      formation from [2]pyruvate. The absence of net carbohydrate synthesis in these
      insects was likely due to an elevation of glycolysis. There was no significant
      effect of diet consumption or parasitism on blood trehalose level. Parasitized
      larvae displayed higher levels of gluconeogenesis than did unparasitized insects,
      a finding consistent with the conclusion that blood sugar is rapidly sequestered
      by developing parasites. The parasite burden, the total number of parasites
      developing within host larvae, as well as the number of parasites emerging from
      host larvae to complete development, was significantly less at the lowest dietary
      nutrient level, but was otherwise similar at all dietary nutrient levels.
      Moreover, the number of parasites that emerged increased with increasing diet
      consumption as reflected by host final weight.

PMID- 12049795
TI  - Biochemical properties of the stimulatory activity of DNA polymerase alpha by the
      hyper-phosphorylated retinoblastoma protein.
AB  - Previously, my colleagues and I have reported that the immunopurified hyper
      phosphorylated retinoblastoma protein (ppRb) stimulates the activity of DNA
      polymerase alpha. I describe here the biochemical characteristics of this
      stimulatory activity. DNA polymerase alpha-stimulatory activity of ppRb was most
      remarkable when using activated DNA as a template-primer, rather than using
      poly(dT)-(rA)(10), poly(dA)-(dT)(12-18), and so on. Kinetic analysis showed that
      there was no significant difference in K(m) value for deoxyribonucleotides of DNA
      polymerase alpha in the presence of ppRb. Adding ppRb resulted in the overcoming
      pause site on the template, but did not affect the rate of misincorporation of
      incorrect deoxyribonucleotides. By adding ppRb, the optimal concentration of
      template-primer was shifted to a higher region, but not using M13 singly primed
      DNA. The ppRb seemed to assist the process that DNA polymerase alpha changed its
      conformation resulting in appropriate enzyme activity. These results suggest that
      ppRb affects both template-primer and DNA polymerase alpha and makes appropriate
      circumstances for the enzyme reaction.

PMID- 12049796
TI  - Metal ions as potential regulatory factors in the biosynthesis of red hair
      pigments: a new benzothiazole intermediate in the iron or copper assisted
      oxidation of 5-S-cysteinyldopa.
AB  - In the presence of iron or copper ions, the course of the oxidation in air of 5-S
      cysteinyldopa (1), the main biosynthetic precursor of pheomelanins and
      trichochromes, was markedly changed affording two main products. One of these was
      identified as the oxobenzothiazine 8, previously obtained under
      nonphysiologically relevant conditions, while the other was characterized as the
      novel hydroxybenzothiazole 9. Besides 8 and 9, carboxylated and noncarboxylated
      benzothiazine products were obtained by persulfate oxidation of 1 in the presence
      of iron or copper ions. The ratio of formation yields of
      carboxylated/noncarboxylated benzothiazines, determined after reduction of the
      mixture, was lower than that of the control reaction run in the absence of metal
      ions, and much lower than that of the oxidation carried out in the presence of
      zinc ions, in agreement with a recent report. Notably, 8 and 9 were formed in
      variable yields under different oxidation conditions including tyrosinase/O(2),
      peroxidase/hydrogen peroxide, and the hydrogen peroxide/or (9E,11Z,13S)-13
      hydroperoxyoctadeca-9,11-dienoic acid/Fe(III) systems. Mechanistic routes to 8
      and 9 were proposed based on the results of experiments involving in situ
      generation of labile benzothiazine intermediates. Overall, these results allow to
      formulate an improved biosynthetic scheme in which metal ions act as critical
      regulatory factors determining pheomelanin vs. trichochromes formation.

PMID- 12049797
TI  - The ictal EEG as a predictive factor for outcome following corpus callosum
      section in adults.
AB  - Published reports have indicated that after callosotomy half or more of all
      patients will experience a 50% or greater reduction in seizure frequency. Those
      callosotomy patients whose seizures produce falls appear to have the best
      results. We studied the value of ictal EEG in 41 patients 18 years or older who
      had undergone either a total or partial callosotomy at our program. Ictal EEG's
      were separated into two categories: Type I: generalized slow spike wave,
      electrodecrement, non-evolving low amplitude fast activity; Type II: all other
      patterns. Types I and II were then compared to a defined one-year outcome for the
      targeted seizure type using Chi-square or Fishers Exact Test. Previously
      identified predictors of good or worthwhile outcome as defined by the literature
      were also evaluated. RESULTS: A significant association was noted for presence of
      specifically defined EEG patterns and a 90% reduction in seizure frequency but
      not for other factors analyzed. CONCLUSION: The ictal EEG but not other factors
      is able to identify a group of patients who have a better than 90% chance for
      total or nearly total resolution of seizures causing sudden falls.

PMID- 12049798
TI  - The ketogenic diet upregulates expression of the gene encoding the key ketogenic
      enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in rat brain.
AB  - The ketogenic diet is a clinically and experimentally effective anti-epileptic
      treatment whose molecular mechanism(s) of action remain to be elucidated. As a
      first step in defining its effects on regulation of fatty acid oxidation and
      ketogenesis at the genetic level, we have administered to rats: (1) a calorie
      restricted ketogenic diet (KCR); (2) a calorie-restricted normal diet (NCR); or
      (3) a normal diet ad libitum (NAL). We have used RNase protection to co-assay
      diet-induced changes in abundance of the mRNA encoding the critical enzyme of
      ketogenesis from acetyl-CoA namely mitochondrial 3-hydroxy-3-methylglutaryl-CoA
      synthase (mHS) in liver and brain, together with mRNAs encoding three other key
      enzymes of fatty acid oxidation. We demonstrate that NCR-fed rats exhibit a
      significant 2-fold increase in liver mHS mRNA compared to NAL-fed rats, and that
      KCR-fed rats exhibit a significant 2-fold increase in both liver and brain mHS
      mRNA compared to NAL-fed rats. Our results demonstrate, for the first time, the
      effect of a ketogenic diet on gene expression in brain, and suggest possible anti
      epileptic mechanisms for future investigation.

PMID- 12049799
TI  - Pilocarpine-induced status epilepticus results in mossy fiber sprouting and
      spontaneous seizures in C57BL/6 and CD-1 mice.
AB  - Several rodent models are available to study the cellular mechanisms associated
      with the development of temporal lobe epilepsy (TLE), but few have been
      successfully transferred to inbred mouse strains commonly used in genetic
      mutation studies. We examined spontaneous seizure development and correlative
      axon sprouting in the dentate gyrus of CD-1 and C57BL/6 mice after systemic
      injection of pilocarpine. Pilocarpine induced seizures and status epilepticus
      (SE) after systemic injection in both strains, although SE onset latency was
      greater for C57BL/6 mice. There were also animals of both strains which did not
      experience SE after pilocarpine treatment. After a period of normal behavior for
      several days after the pilocarpine treatment, spontaneous tonic-clonic seizures
      were observed in most CD-1 mice and all C57BL/6 that survived pilocarpine-induced
      SE. Robust mossy fiber sprouting into the inner molecular layer was observed
      after 4-8 weeks in mice from both strains which had experienced SE, and cell loss
      was apparent in the hippocampus. Mossy fiber sprouting and spontaneous seizures
      were not observed in mice that did not experience a period of SE. These results
      indicate that pilocarpine induces spontaneous seizures and mossy fiber sprouting
      in both CD-1 and C57BL/6 mouse strains. Unlike systemic kainic acid treatment,
      the pilocarpine model offers a potentially useful tool for studying TLE
      development in genetically modified mice raised on the C57BL/6 background.

PMID- 12049800
TI  - Clinical effects of topiramate against secondarily generalized tonic--clonic
      seizures.
AB  - OBJECTIVE: Intensive and quantitative evaluation of the duration, intensity and
      frequency of tonic and clonic signs of secondarily generalized tonic-clonic
      seizures (GTCS) in patients with pharmacoresistant partial seizures during
      topiramate (TPM) treatment. METHODS: Thirty patients suffering from refractory
      partial seizures with secondarily GTCS undergoing presurgical evaluation were
      randomized into a low dosage (100 mg daily) and a parallel medium dosage (200 mg
      daily) group of TPM add-on medication (15 patients for each group). Study phases
      included a 3 days baseline video-EEG phase, a 10 days TPM titration phase without
      video-EEG and a 3 days TPM dose maintenance phase with video-EEG. During the
      baseline and the dose maintenance phase seizures were recorded using video-EEG
      monitoring and the following parameters were measured for each recorded
      secondarily generalized tonic and clonic signs: duration (lasting seconds),
      intensity (on a 0-3 scale), frequency (numbers per 24 h). RESULTS: A total of 46
      complex partial seizures with secondarily generalized tonic-clonic signs during
      the baseline phase and 20 during the dose maintenance phase were intensively
      analyzed. More patients in the medium dosage group than in the low dosage groups
      were free from secondarily GTCS during the dose maintenance phase (nine vs. two,
      P<0.05). Intergroup comparison suggested that the duration of all tonic signs
      decreased more in the medium dosage group computing the reduction from baseline
      to the dose maintenance phase (P<0.05). There were statistically more significant
      reductions in the duration and intensity of clonic signs in the medium dosage
      group (P<0.05). CONCLUSION: TPM has an early dose-dependant effect on secondarily
      GTCS in patients with pharmacoresistant partial seizures. SHORT COMMUNICATION:
      The present study intensively analyzed the duration, intensity, and frequency of
      secondarily generalized tonic and clonic signs in patients with pharmacoresistant
      partial seizures. The quantitative data suggested that TPM had a robust early
      inhibitory effect on secondarily generalized tonic-clonic signs; effects were
      more prominent in the medium dosage group (200 mg daily) than in the low dosage
      group (100 mg daily).

PMID- 12049801
TI  - The involvement of endogenous opioids and nitricoxidergic pathway in the
      anticonvulsant effects of foot-shock stress in mice.
AB  - The involvement of endogenous opioids and nitric oxide (NO) in the anticonvulsant
      effects of stress against pentylenetetrazole (PTZ)- or electroconvulsive shock
      induced seizures was assessed in mice. The prolonged and intermittent foot-shock
      stress, which induced opioid-mediated analgesia, had significant protective
      effects against both seizure types which was reversible by naloxone (0.3, 1 or 2
      mg/kg), while brief and continuous foot-shock did not alter the seizure
      susceptibility. Pre-treatment with non-specific nitric oxide synthase (NOS)
      inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 1, 2, 5, 10 or 30 mg/kg),
      but not with specific inducible NOS (iNOS) inhibitor, aminoguanidine (50 or 100
      mg/kg), blocked the stress-induced anticonvulsant effects. The lower doses of
      naloxone (0.3 mg/kg) and L-NAME (2 mg/kg) showed additive effects in blocking the
      stress-induced anticonvulsant properties. L-arginine at a per se non-effective
      dose of 20 mg/kg potentiated the stress-induced anticonvulsant properties, an
      effect which was inhibited by L-NAME but not by aminoguanidine. Furthermore, a
      low dose of morphine (0.5 mg/kg) showed potentiation with stress in increasing
      PTZ seizure threshold. This potentiation was reversed by either naloxone or L
      NAME at low doses but not by aminoguanidine. Taken together, these results show
      that NO synthesis, through constitutive but not iNOS, is involved in opioid
      dependent stress-induced anticonvulsant effects against electrical and PTZ
      induced convulsions.

PMID- 12049802
TI  - Effects of antiepileptic drugs on extracellular pH regulation in the hippocampal
      CA1 region in vivo.
AB  - Intracellular and extracellular pH are known to influence neuronal activity and
      may play a role in seizure termination. In the pyramidal cell layer of the CA1
      region of the hippocampus in the urethane anesthetized adult rat, there is an
      initial alkalinization in response to stimulus trains administered to the
      contralateral CA3 region. This is followed by an acidification that peaks after
      termination of the afterdischarge. Initial experiments demonstrated that the peak
      level of acidification correlated with the duration of the afterdischarge, but
      that the peak level of alkalinization did not. The effects of several
      antiepileptic drugs on the initial alkalinization were determined. Systemic
      administration of acetazolamide (50 mg/kg, n=4) and topiramate (45 mg/kg, n=7)
      and local administration of benzolamide (n=3), all of which inhibit carbonic
      anhydrase, decreased the initial alkalinization that occurs during the stimulus
      train. Diazepam (3 mg/kg, n=5) and phenobarbital (60 mg/kg, n=6), agonists at the
      GABA(A) receptor complex, increased the initial alkalinization, while sodium
      channel blockers phenytoin (80 mg/kg, n=5) and carbamazepine (50 mg/kg, n=5) had
      no significant effect. The data suggest that the alkalinization in CA1 in vivo is
      predominantly regulated through activity of the GABA(A) receptor, rather than
      through activation of glutamatergic receptors. The change in alkalinization does
      not appear to be related to the mechanism of the antiepileptic effect of the
      drugs that were tested.

PMID- 12049803
TI  - Depressive disorders preceding temporal lobe epilepsy.
AB  - In this study, we investigated three female patients given a diagnosis of
      temporal lobe epilepsy preceded by depression. It is notable that all the
      patients complained of abnormal sensations, either in the throat or oral. The
      depression in the three patients showed no improvement with antidepressants, but
      carbamazepine was effective for both epileptic seizures and depression. EEG
      should be performed on patients who develop antidepressant treatment-refractory
      depression accompanied by hypochondriacal complaints.

PMID- 12049804
TI  - Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic
      epilepsy locus (EJM2) on chromosome 15q13-14.
AB  - A previous study of 34 nuclear pedigrees segregating juvenile myoclonic epilepsy
      (JME) gave significant evidence of linkage with heterogeneity to marker loci on
      chromosome 15q13-14 close to the candidate gene CHRNA7 (Hum. Mol. Genet. 6 (1997)
      1329). The aim of this work was to further evaluate the putative aetiological
      role of CHRNA7 in JME within the 34 families originally described, and to assess
      the contribution of this locus to a broader phenotype of idiopathic generalised
      epilepsy (IGE). Multipoint linkage analysis and intrafamilial association studies
      were performed with microsatellite markers that encompass both CHRNA7 and its
      partial duplication (CHRFAM7A). A maximum HLOD of 3.45 [alpha=0.58; (Zall=2.88,
      P=0.0008)] was observed 8 cM distal to D15S1360, a CHRNA7 intragenic marker.
      Significant exclusion lod scores were obtained across the region in 12 mixed
      phenotype JME/IGE families. Mutation screening of the CHRNA7 gene (and
      consequently exons 5-10 of CHRFAM7A) and its putative promoter sequence
      identified a total of 13 sequence variants across 23 of 34 JME-affected families.
      Two variants (c.1354G>A and c.1466C>T) are predicted to result in amino acid
      changes and one (IVS9+5G>A) is predicted to result in aberrant transcript
      splicing. However, none of the variants alone appeared either necessary or
      sufficient to cause JME in the families in which they occurred. In conclusion,
      linkage analyses continue to support the existence of a locus on chromosome 15q13
      14 that confers susceptibility to JME but not to a broader IGE phenotype. Causal
      sequence variants in the positional candidate CHRNA7 have not been identified but
      the presence of multiple segmental duplications in this region raises the
      possibility of undetected disease-causing genomic rearrangements.

PMID- 12049805
TI  - Failure to replicate an allelic association between an exon 8 polymorphism of the
      human alpha(1A) calcium channel gene and common syndromes of idiopathic
      generalized epilepsy.
AB  - The present replication study tested the validity of a previously reported
      allelic association between a single nucleotide polymorphism in exon 8 (SNP8) of
      the gene encoding the alpha(1A)-calcium channel subunit (CACNA1A) and common
      subtypes of idiopathic generalized epilepsy (IGE). Pyrosequencing was applied to
      assess the SNP8 genotypes in 354 unrelated German IGE probands, both parents of
      118 IGE probands, and 186 healthy control subjects of German descent. Our
      population-based association analysis did not provide evidence for an allelic
      association of SNP8 with either IGE or two phenotypically more homogeneous IGE
      subtypes, consisting of either 139 probands with juvenile myoclonic epilepsy or
      207 probands whose IGE started with typical absence seizures (P>0.72). In
      addition, the transmission disequilibrium test did not indicate a preferential
      transmission of SNP8 alleles in 97 informative parent-child transmissions
      (McNemar chi(2)=0.093, df=1, P=0.76). Accordingly, we failed to confirm previous
      evidence that genetic variation of the CACNA1A gene confers susceptibility to
      common IGE syndromes.

PMID- 12049808
TI  - Inhibitory effect of peptide Epitalon on colon carcinogenesis induced by 1,2
      dimethylhydrazine in rats.
AB  - The effect of synthetic pineal peptide Epitalon (Ala-Glu-Asp-Gly) on colon
      carcinogenesis was firstly studied in rats. Eighty 2-month-old outbred male LIO
      rats were subdivided into four groups and were weekly exposed to five
      subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21
      mg/kg body weight. Additionally, 5 days a week, some of the rats were given
      subcutaneous injections of saline at a dose of 0.1 ml during the whole experiment
      (group 1, control) or Epitalon at a single dose of 1 microg during the whole
      experiment (group 2), Epitalon after termination of carcinogen injections (group
      3) or during the period of DMH exposure (group 4). Colon carcinomas developed in
      90-100% of DMH-treated rats. The number of total colon tumors per rat was 4.1;
      2.7; 3.7; 2.9 in groups 1, 2, 3, 4, respectively (the difference in groups 2 and
      4 compared with group 1 is significant). In rats from group 2, colon tumors were
      smaller than in control animals. In group 2, the incidence, as well the
      multiplicity of tumors in ascending and descending colon, were significantly
      decreased in comparison with group 1. In group 4, the mean number of tumors per
      rat was significantly decreased, too. A trend to decrease the number of tumors in
      the rectum in rats from groups 2, 3 and 4, treated with Epitalon was found.
      Epitalon inhibited also the development of tumors in jejunum and ileum. Thus, our
      results demonstrated an inhibitory effect of Epitalon on chemically induced bowel
      carcinogenesis in rats.

PMID- 12049809
TI  - Inhibitory effects of lemon grass (Cymbopogon citratus, Stapf) extract on the
      early phase of hepatocarcinogenesis after initiation with diethylnitrosamine in
      male Fischer 344 rats.
AB  - Effects of lemon grass extract (LGE) on hepatocarcinogenesis were examined in
      male Fischer 344 rats, administered diethylnitrosamine (DEN) at three weekly
      intraperitoneal doses of 100 mg/kg body weight and partially hepatectomized at
      the end of week 5. LGE was given at dietary concentrations of 0, 0.2, 0.6 or 1.8%
      from the end of week 4 for 10 weeks. All rats were sacrificed at the end of week
      14. LGE reduced the number of putatively preneoplastic, glutathione S-transferase
      placental form-positive lesions and the level of oxidative hepatocyte nuclear DNA
      injury, as assessed in terms of 8-hydroxydeoxyguanosine production. In contrast,
      LGE did not affect the size of the preneoplastic lesions, hepatocyte
      proliferative activity, activities of phase II enzymes or hepatocyte extra
      nuclear oxidative injury. These results suggest inhibitory effects of LGE on the
      early phase hepatocarcinogenesis in rats after initiation with DEN.

PMID- 12049810
TI  - Suppression of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced DNA damage
      in rat colon after grapefruit juice intake.
AB  - The influence of grapefruit juice intake on 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP)-induced colon DNA damage was examined using comet assay in F344
      rats given 60 mg/kg of PhIP by gavage. F344 rats allowed free access to
      grapefruit juice for 5 days experienced clearly reduced DNA damage in the colon
      to a 40% level of control rats. The suppression of PhIP-induced colon DNA damage
      depended on the grapefruit juice concentrations. The serum concentration of PhIP
      was compared between grapefruit juice-pretreated and non-pretreated rats, but
      showed no significant difference in the areas under their concentration-time
      curves, peak values and half lives of PhIP. Furthermore, no obvious difference
      was found in the liver capacity for mutagenic activation of PhIP in Ames assay
      between grapefruit juice-pretreated and non-pretreated rats. These results
      suggest that grapefruit juice suppresses PhIP-induced colon DNA damage by a
      mechanism independent of PhIP absorption in the intestine.

PMID- 12049811
TI  - Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma.
AB  - Isoliquiritigenin is a chalcone isolated from licorice and shallots. The ability
      of isoliquiritigenin to suppress metastasis was examined in a pulmonary
      metastasis model of mouse renal cell carcinoma. Isoliquiritigenin significantly
      reduced pulmonary metastasis, without any weight loss or leukocytopenia.
      Isoliquiritigenin suppressed in vitro proliferation of carcinoma cells,
      potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages,
      and facilitated cytotoxicity of splenic lymphocytes in vitro. These findings
      suggest activation of macrophages, activation of cytotoxicity of lymphocytes, and
      direct cytotoxicity as possible mechanisms of metastasis suppression by
      isoliquiritigenin. In addition, isoliquiritigenin prevented severe leukocytopenia
      caused by administration of 5-fluorouracil.

PMID- 12049812
TI  - Enhanced colon carcinogenesis induced by azoxymethane in min mice occurs via a
      mechanism independent of beta-catenin mutation.
AB  - The multiple intestinal neoplasia (min) mouse is a well-established cancer model
      in which loss of a single copy of the APC protein predisposes mice to the
      development of numerous tumors in the intestine. We have developed a novel
      variation of the min mouse model by using azoxymethane (AOM) to cause an increase
      in tumor incidence, number and size. Thus, treatment of min mice with AOM
      resulted in 2.6-, 6.3- and 5.9-fold increases in overall tumor incidence,
      multiplicity and size, respectively, when compared to wild type C57BL/6J mice
      treated with AOM. Furthermore, adenocarcinomas of the colon, which are otherwise
      relatively rare in min mice, increased in incidence (P<0.004), multiplicity
      (P<0.005), and size (P<0.02) in the AOM-treated min mice when compared to control
      untreated min mice. Of these adenocarcinomas, the number of poorly plus
      moderately differentiated adenocarcinomas was also significantly higher in the
      AOM-treated min mice (P<0.008). Thirty-seven histopathologically verified colon
      tumors (eight adenomas, five carcinoma in situ and 24 adenocarcinomas) induced in
      min mice and in C57BL/6J mice after treatment with or without AOM were analyzed
      for mutations in the beta-catenin gene or de novo mutations in the Apc gene. No
      mutations in the beta-catenin gene were found in any of colon tumors in min mice
      with or without treatment with AOM. However, mutations in either the beta-catenin
      gene or the Apc gene were found in tumors induced in C57BL/6J mice by AOM. These
      results suggest that mutations in the beta-catenin gene are less contributory to
      tumor development in min mice, as is the case in familial adenomatous polyposis
      (FAP) in humans. However, de novo mutations in either the Apc or beta-catenin
      gene can play a role in tumor development in C57BL/6J mice treated with AOM. The
      differences in mutation status between min and C57BL/6J mice may indicate
      different genetic pathways for developing colon tumors. These two experimental
      systems may, therefore, be useful animal models of human colon carcinomas in
      patients with FAP and in patients with sporadic colon carcinomas.

PMID- 12049813
TI  - Mediators of peripheral blood neutrophilia induced by photodynamic therapy of
      solid tumors.
AB  - Photodynamic therapy (PDT) of tumors elicits a strong host immune response and
      one of its manifestations is a pronounced neutrophilia. By blocking their
      function prior to Photofrin-based PDT of mouse EMT6 tumors, we have identified
      multiple mediators whose regulated action is responsible for this neutrophilia.
      In addition to complement fragments (direct mediators) released as a consequence
      of PDT-induced complement activation, there are at least a dozen secondary
      mediators that all arise as a result of complement activity. The latter include
      cytokines IL-1beta, TNF-alpha, IL-6, IL-10, G-CSF and KC, thromboxane,
      prostaglandins, leukotrienes, histamine, and coagulation factors.

PMID- 12049814
TI  - Novel benzimidazole derivatives selectively inhibit endothelial cell growth and
      suppress angiogenesis in vitro and in vivo.
AB  - We discovered a novel benzimidazole derivative, named compound (comp.) 1, with
      unique antiangiogenic characteristics. Comp.1 cytostatically inhibited the
      vascular endothelial growth factor- and basic fibroblast growth factor-induced
      growth of endothelial cells (50% inhibitory concentration: 29-79 nM) without a
      cytotoxic phase, but did not affect the growth of other types of cells up to 90
      microM. Comp.1 also inhibited the tube formation derived from a rat aorta
      fragment, but the oral (p.o.) treatment of comp.1 (46 mg/kg, administered twice
      daily (b.i.d.)) did not inhibit aniogenesis in a mouse sponge model. Comp.8, an
      analogue of comp.1, showed a specific inhibitory effect on endothelial cell
      growth. Comp.8 also suppressed angiogenesis (15 mg/kg, b.i.d., p.o., 70%
      inhibition) in the sponge model without body weight loss.

PMID- 12049815
TI  - In vitro cytotoxic potential and mechanism of action of selected coumarins, using
      human renal cell lines.
AB  - This study determined the selective cytotoxicity of eight coumarin compounds to
      human renal carcinoma cells, relative to non-carcinoma proximal tubular cells.
      Selectivity cytotoxicity was observed following exposure to 6-nitro-7
      hydroxycoumarin (6-NO(2)-7-OHC) and 7,8-dihydroxycoumarin (7,8-OHC). 6-NO(2)-7
      OHC induced cytotoxicity was irreversible in both cell lines, unlike 7,8-OHC,
      which was reversible in the carcinoma cells only. Mobility shift and BrdU
      incorporation assays showed that both compounds did not intercalate DNA but had a
      concentration-dependent inhibitory effect on its synthesis. All coumarins studied
      were found to be non-mutagenic using the standard Ames test. These results would
      suggest that 6-NO(2)-7-OHC and 7,8-OHC might have a therapeutic role to play in
      the treatment of renal cell carcinoma.

PMID- 12049817
TI  - Isolation of a novel mouse variant of the drs tumor suppressor gene.
AB  - The drs gene was isolated as a transformation suppressor against the v-src
      oncogene. Drs protein has a transmembrane domain and three consensus repeats
      (CRs) called Sushi motifs in the extracellular domain. The drs gene also has the
      ability to suppress anchorage-independent growth of human cancer cell lines. In
      this paper, we report the isolation of a novel variant cDNA of mouse drs (mDRS-2)
      containing two CRs, in addition to a mouse homolog of drs (mDRS-1) containing
      three CRs. We investigated the suppressor function of these mDRS cDNAs in human
      cancer cells and found that the lack of one CR is critical for suppression of
      anchorage-independent growth by drs.

PMID- 12049816
TI  - The initial evaluation of non-peptidic small-molecule HDM2 inhibitors based on
      p53-HDM2 complex structure.
AB  - Peptidic Mouse Double Minute (MDM2) inhibitors have been demonstrated to
      effectively inhibit the interaction between p53 and MDM2, thus providing a
      therapeutic strategy for some tumors. However, there is no report on non-peptidic
      inhibitors. In this study non-peptidic HDM2 (the human homologue of MDM2)
      inhibitors were obtained by computer-aided design and subsequently synthesized by
      chemical method. Bio-evaluation showed that some of these inhibitors have
      affinity with HDM2, and can cause death of some tumor cells which express wild
      type p53. Cellular assays showed that one of these compounds, syc-7, can activate
      the p53 pathway in some of these tumor cell lines, and further induce apoptosis.
      The results suggest that developing non-peptidic small-molecule HDM2 inhibitors
      is a promising way for new antitumor drug discovery.

PMID- 12049818
TI  - The AF2 domain of the orphan nuclear receptor TEC is essential for the
      transcriptional activity of the oncogenic fusion protein EWS/TEC.
AB  - The EWS/TEC fusion protein encoded by the t(9:22) chromosomal translocation in
      human extraskeletal myxoid chondrosarcoma tumors is thought to participate in the
      tumoral process at least in part by deregulating the expression of specific
      target genes involved in the control of cell proliferation. In this work we show
      that the activation function-2 (AF2) domain of TEC is essential for the
      transcriptional activity of the EWS/TEC fusion protein. Significantly, deleting
      only the last 15 amino acids of the fusion protein, which contains 949 amino
      acids in its full form, results in a loss of over 70% of its transcriptional
      activity in transfected human chondrocyte cell lines. Point mutation analyses
      indicate that within the AF2 domain, amino acid residues I939, D940 and F943 all
      play a crucial role in the activity of EWS/TEC. Comparable results were obtained
      with the native TEC receptor. These results suggest that EWS/TEC interacts at
      least in part with the same transcriptional coactivators as the native TEC
      receptor, and that these coactivators may be involved in the tumoral process
      leading to human chondrosarcoma tumors.

PMID- 12049819
TI  - Differential expression of Wnt genes, beta-catenin and E-cadherin in human brain
      tumors.
AB  - Wnt regulates developmental and oncogenic processes through its downstream
      effector, beta-catenin, and a set of other intracellular regulators that are
      largely conserved among species. E-cadherin was discovered as a protein
      associated with beta-catenin which plays a crucial role in cell-cell adhesion. To
      further understand the molecular basis of Wnt signaling pathway and E-cadherin in
      brain tumorigenesis, the expression of four Wnt genes (Wnt1, Wnt5a, Wnt10b and
      Wnt13) and E-cadherin were analyzed by reverse transcriptase-polymerase chain
      reaction. In addition, their downstream effector, beta-catenin, was also
      investigated. The results showed that the expression of Wnt5a (41/45), Wnt10b
      (37/45), and Wnt13 (35/45) were found in brain tumors, whereas Wnt1 (6/45) was
      shown to be less related. Interestingly, E-cadherin was only expressed in a few
      cases of astrocytoma (2/16), whereas it was expressed in most meningioma (14/15)
      and pituitary adenoma tumors (12/14). There was no apparent difference of beta
      catenin expression profile in brain tumors; however, the sequencing data of beta
      catenin showed two mutations on speculative phosphorylation sites, S73F and S23G
      in astrocytoma. Furthermore, an in vitro functional assay showed that S73F and
      S23G mutants of beta-catenin did not affect transcriptional activity in TCF-4
      leuciferase reporter construct, suggesting that they may need more complex
      factors to participate in astrocytoma. Taken together, our data suggest that the
      mutations of beta-catenin together with E-cadherin and Wnt signaling might be
      involved in brain tumorigenesis.

PMID- 12049820
TI  - Staurosporine-induced G(1) arrest in cancer cells depends on an intact pRB but is
      independent of p16 status.
AB  - Staurosporine and its derivative 7-hydroxystaurosporine are protein kinase
      inhibitors that are being considered for treatments of cancers. Several recent
      studies have shown that cells with defective pRB protein are resistant to the
      G(1) cell cycle-inhibiting effects of staurosporine compounds. In this study, we
      examined the effect of staurosporine on two breast cancer-derived and three lung
      cancer-derived cell lines characterized by deficiencies in the p16 tumor
      suppressor. All of these p16-deficient cell lines are highly sensitive to
      staurosporine-induced inhibition of pRB phosphorylation and induction of arrest
      in G(1). This response is similar to that seen in cultured normal human bronchial
      epithelial cells and normal mammary epithelial cells, but strikingly different
      than the staurosporine resistance seen in cancer cells with defective pRB.
      Interestingly, inhibition of pRB phosphorylation could be seen within 4 h of
      treatment, suggesting that this inhibition is a consequence of direct effects of
      staurosporine on protein kinase(s) rather than a result of induction of other
      cyclin-dependent kinase inhibitors. Our findings suggest that different types of
      cancer cells have vastly different responses to the staurosporine class of
      agents, and that evaluation of pRB and p16 will help predict the response of the
      cancer cells to these agents.

PMID- 12049821
TI  - Diagnostic certainty for acute otitis media.
AB  - Our primary objective was to assess diagnostic accuracy for acute otitis media
      (AOM) relative to the criterion standard established by the United States Agency
      for Healthcare Research and Quality: middle-ear effusion (MEE) plus onset in the
      past 48 h of signs or symptoms of middle-ear inflammation. A secondary objective
      was to assess the potential reduction in antibiotic usage that could be achieved
      if clinicians managed AOM according to a consensus guideline developed by the New
      York Region Otitis Project (NYROP). A convenience sample of primary care
      practitioners were surveyed after diagnosing AOM in 135 children aged 0.3-11.8
      years (median 2.4 years). Clinicians expressed high certainty for AOM diagnosis
      in 122/135 episodes (90%). The prevalence of true AOM was 70% with a positive
      predictive value for high certainty of 76%. Of the 40 false-positive diagnoses,
      35 did not have MEE and 5 did not have acute signs or symptoms. The relative risk
      for receiving an antibiotic was 1.50 times higher when clinicians expressed
      certainty (P=0.005), which produced 31/120 (26%) potentially unnecessary
      antibiotic prescriptions. Initial antibiotics would not have been prescribed for
      29% of episodes using the NYROP guidelines. More judicious use of antibiotics may
      result if clinicians deferred initial therapy in children without definitive AOM,
      particularly when the presence of MEE is uncertain.

PMID- 12049822
TI  - Development of the vocal fundamental frequency of spontaneous cries during the
      first 3 months.
AB  - Studies in the field of cry diagnosis have concentrated on the fundamental
      frequency (F(0)) and related parameters as suitable predictors for an at-risk
      status of the infant for a CNS dysfunction, mostly reflected in an increased
      F(0). The high variability of F(0) in infant cries is a limiting factor to
      develop cry analysis as a non-invasive tool for early diagnosis. As only a few
      longitudinal studies were carried out, our case study wants to contribute to
      provide developmental data on fundamental frequency of infant cries with a
      considerable higher time resolution (shorter recording interval). The fundamental
      frequency of spontaneous cries of one male infant was analyzed using KAY-CSL 4300
      for its daily characteristics during the first 3 months of life. This dense
      sampling interval (daily recordings) enabled the description of the range of
      temporary changes of the fundamental frequency during the observation period. The
      mean fundamental frequency values of cries uttered at single days and of the
      cries of successive days were relatively variable. In contrast to former studies,
      no significant decreasing or increasing trend of the mean fundamental frequency
      of all analyzed cries was found through the first 3 months of life. Only cries
      shorter than 0.8 s showed an increasing developmental trend of the mean F(0).

PMID- 12049824
TI  - Receptive and expressive language skills of 106 children with a minimum of 2
      years' experience in hearing with a cochlear implant.
AB  - OBJECTIVE: The aim of the study was to assess the speech development of children
      with at least 2 years' hearing experience with a cochlear implant (CI). METHODS:
      One hundred and six children were tested, all of whom had used the CI for at
      least 2 years. Receptive and expressive language development were tested using
      the scales of early communication skills for hearing-impaired children after
      Geers and Moog and the Reynell developmental language scales III. In addition,
      free-field audiometry was performed. Pre-postoperative measurements were compared
      statistically, and a linear regression analysis was carried out. RESULTS: Clear
      improvements in the gain in functional hearing 2 years after receiving the CI as
      well as clear improvements in both speech perception and speech production were
      ascertained. All deviations were statistically highly significant (P<0.000). The
      receptive and expressive speech test results correlate positively to a great
      extent. The results of logistic regressive analysis indicate that the speech
      production measured depends decisively on age at implantation, age at time of
      test, speech production before implantation, and additional handicaps.
      CONCLUSION: Based on the conception of the WHO, a statistically significant
      improvement of both impairment and disability can be confirmed. In the present
      study, the regression analysis established the age at implantation as the most
      important prognostic factor. While the percentage of children with good speech
      development is larger with early implanted children than with late implanted
      children, some of the children among the early implanted group show
      unsatisfactory speech development of unknown origin. Improvements in speech
      development are likely to be achieved when more children are diagnosed and
      implanted early. This finding urgently requires the introduction of a general
      newborn screening program. Thorough anamnesis and assessment during parent
      counseling of the manifold factors described are a prerequisite for the precise
      estimation of the difficulties to be met and the expected effectiveness of the
      implant in each individual case.

PMID- 12049823
TI  - Hearing impairment and ear diseases among children of school entry age in rural
      South India.
AB  - OBJECTIVE: To find out the prevalence and causes of hearing impairment among
      children of school-entry age, in rural areas of coastal south India. METHODS: The
      study adopted the World Health Organization (WHO) guidelines viz., "The
      Prevalence of Ear and Hearing Disorders Protocol". A total of 855 children
      studying in the first year of school were examined using a Portable Pure Tone
      Audiometer and an Otoscope. Children with hearing impairment were re-examined to
      find out the type of hearing impairment. Mothers of all children were interviewed
      in their homes, in order to obtain details of socio-economic status, family
      history and history of consanguinity. RESULTS: Hearing impairment was detected in
      102 children (11.9%) and impacted wax was found to be the most common cause of
      hearing impairment (86.3%). On re-testing, it was predominantly conductive
      hearing impairment (81.6%) observed among 74 of these children. The prevalence of
      hearing impairment was significantly lower among children belonging to high socio
      economic status (P=0.0036). CONCLUSIONS: Hearing impairment and preventable ear
      diseases were found to be important health problems among children of school
      entry age group in this region. Regular screening of children of school-entry age
      will ensure that children begin their school-life without this disability.

PMID- 12049825
TI  - Implication of immunological abnormalities after adenotonsillotomy.
AB  - The adenoids and tonsils are thought to be essential parts of the system
      protecting organism against pathogens invading the upper respiratory tracts.
      Human adenoids and tonsils are known to be immunologically reactive lymphoid
      organs, which manifest specific antibodies and B and T cells activity in response
      to variety of antigens carrying out the functions of humoral and cellular
      immunity. The purpose of the study was to observe the changes in systemic
      immunity in children with hypertrophy of adenoids and tonsils treated in
      Department of Laryngology, Children's Hospital in Warsaw in period 1994-1999. The
      study comprised 80 patients (33 girls and 47 boys, aged from 3 to 14 years, mean
      age 6.8 years) with diagnosed hypertrophy of adenoids and tonsils. The diagnosis
      of hypertrophy of adenoids and tonsils was based on characteristic history and
      laryngological examination. All patients were scheduled for adenotonsillotomy.
      The control group comprised 40 people (14 girls and 26 boys, aged from 3 to 15
      years, mean age 7.6 years) without history of the recurrent upper tract
      infections. In all patients we carried out following examinations: serum levels
      of immunoglobulins A, G, M (humoral immunity); percentage of T lymphocytes (CD3);
      percentage of T helper (CD4) and T cytotoxic (CD8) lymphocytes (cellular
      immunity) and delayed cutaneous hypersensitivity-Multitest CMI (cell mediated
      immunity). Our study demonstrate that in children with hypertrophy of adenoids
      and tonsils exist changes in the immunological parameters. The observed changes
      appear not only locally but also generally. In the early period after
      adenotonsillotomy there was statistically significant decrease of the values of
      humoral and cellular immunity parameters. However, 6 months after operation we
      observed normalization of examined immunological parameters. We think that the
      examinations of parameters of immunological system (humoral and cellular) are
      necessary before planned adenotonsillotomy.

PMID- 12049826
TI  - Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to
      vaccination in otitis prone children.
AB  - OBJECTIVE: To evaluate the isotype and IgG subclass distribution of anti
      pneumococcal antibodies and response to polysaccharide vaccination in otitis
      prone children. METHODS: IgG1, IgG2 and IgA antibodies to pneumococcal serotypes
      3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone children and in an
      age-matched healthy control population. Patients were immunized with a 23-valent
      pneumococcal polysaccharide vaccine. The antibody response was measured 4 weeks
      later. RESULTS: Geometric mean IgA and IgG2 antibody levels for all seven
      pneumococcal serotypes tested were significantly lower in otitis prone children
      than in the control population. After immunization, there was no significant
      increase in geometric mean IgG2 anti-serotype 6B, 19F and 23F pneumococcal
      polysaccharide (weak immunogenic), but also no increase for IgG2 anti-serotype 4
      and 14. Post immunization IgG2 antibody titers for serotypes 6B, 9V and 19F even
      remained below titers of non-vaccinated controls. Nine out of 29 otitis prone
      children were colonized nasopharyngeally with Streptococcus pneumoniae during the
      time of vaccination; these children had an even more severely impaired systemic
      antibody response. CONCLUSIONS: Otitis prone children, while having normal IgG1
      antibody levels, have low IgG2 and IgA anti-polysaccharide antibody levels and
      fail to respond in these subclasses upon vaccination with pneumococcal
      polysaccharide vaccine.

PMID- 12049827
TI  - A review of the current management of infantile subglottic haemangioma, including
      a comparison of CO(2) laser therapy versus tracheostomy.
AB  - OBJECTIVES: We reassessed the current practice and treatment options used in the
      management of subglottic haemangiomas (SGHs), including the place for open
      submucosal surgical excision, and have compared the results of different
      therapeutic modalities used for SGHs. METHODS: The two studies were conducted as
      separate exercises; (1) a retrospective review of 36 patients collected over a
      recent 8-year period to assess the current practice and treatment options in use;
      (2) a retrospective comparative study of a previous cohort of 51 patients with
      SGHs treated in one of four groups: (a) tracheostomy alone, (b) tracheostomy and
      CO(2) laser, (c) systemic steroids and CO(2) laser (no tracheostomy) and (d)
      intralesional steroid injection, CO(2) laser therapy, or both, followed by
      intubation. RESULTS: Systemic steroids were the most commonly used modality of
      treatment. Resolution of the SGH was achieved in 89% of cases at a mean follow up
      duration of 34 months. However, tracheostomy was required in 58% of cases, with a
      mean time from diagnosis to decannulation of 30 months. The time to resolution of
      SGHs does not appear to be reduced by laser therapy compared with treatment by
      tracheostomy alone. Intralesional steroid injection or laser therapy together
      with intubation was associated with avoidance of a tracheostomy in 66% of cases.
      Single-stage open surgical excision in two cases resulted in successful
      resolution of the SGH and discharge after a mean follow up period of 3 months.
      CONCLUSIONS: Despite the more widespread use of steroids and other treatment
      modalities, the requirement for tracheostomy has remained unchanged over the last
      20 years. The use of laser therapy does not appear to confer any additional
      therapeutic benefit over and above tracheostomy alone in bringing about
      resolution of SGHs. Systemic steroids may reduce the size of the haemangioma but
      are associated with multiple adverse effects. The decision to use the above
      techniques must, therefore, be made in the light of these observations. Our early
      experience of single-stage excision suggests that this technique represents an
      exciting and promising surgical alternative, and its more widespread adoption may
      be the only way of further improving the outcome of patients with SGHs.

PMID- 12049829
TI  - Carhart's notch: a finding in otitis media with effusion.
AB  - INTRODUCTION: Carhart's notch (CN) is a false depression of bone conduction (BC)
      thresholds at 2-4 kHz initially described in cases of stapes fixation. This study
      was designed to estimate the incidence and assess the clinical significance of CN
      in cases of otitis media with effusion (OME) in children. PATIENTS AND METHODS:
      Clinical records of 50 patients of OME that showed CN were analysed,
      retrospectively. First 24 were identified as seen in outpatients and 26 were
      found out of 100 consecutive cases of OME. The criteria of CN were a minimum 10
      dB depression in BC at any frequency 500-4000 Hz. RESULTS: Fifty patients showed
      CN, with mean age of 8.8 years. All had myringotomies with or without insertion
      of grommets. The CN ranged from 10 to 20 dB in the majority and up to 30 dB in
      few cases. In 85 ears studied, the affected frequencies comprised of 2000 Hz in
      80 (94%), 4000 Hz in 4 and 1000 Hz in one ear. Pre-operative tympanograms were of
      type B in 68 (80%), type C in 16 (18.8%) and type A in one ear. Middle ear fluid
      was thick glue in 57 (67%), serous in 5 (5.8%), and no fluid found in 23 (27%)
      cases. Oedematous, granular or polypoidal appearances of middle ear mucosa were
      noted in 57 (67%) of the ears. A normal mucosa was seen in 17 (20%), and no
      details were available in 11 (13%) ears. Post-operative audiograms showed
      improvements of BC thresholds in 72 (84.7%) of the ears. CONCLUSION: Our results
      show 26% incidence of CN in paediatric cases of OME, with evidence of thick fluid
      and abnormal middle ear mucosa in about two-thirds of cases. This suggests that
      CN may be of prognostic value for myringotomy outcomes. Statistically there is a
      significant correlation between presence of fluid on myringotomy and CN, and type
      of tympanogram and post-operative BC threshold improvement. There is no
      predictive value of CN in terms of character of the middle ear fluid. Studies
      with larger numbers may be required to determine this with more certainty. It can
      help clinically, however, in pre-operative assessment of these cases. It is our
      opinion that BC should be an essential part of routine audiometry in all cases of
      OME.

PMID- 12049828
TI  - Comparison of speech perception benefits with SPEAK and ACE coding strategies in
      pediatric Nucleus CI24M cochlear implant recipients.
AB  - Nine congenitally deaf children who received a Nucleus CI24M cochlear implant and
      who were fitted with the SPrint speech processor participated in this study. All
      subjects were initially programmed with the SPEAK coding strategy and then
      converted to the ACE strategy. Speech perception was evaluated before and after
      conversion to the new coding strategy using word and Common Phrase speech
      recognition tests in both the presence and absence of noise. In quiet conditions,
      the mean percent correct scores for words were 68.8% with SPEAK and 91% with ACE;
      for phrases the percentage was 66.6% with SPEAK and 85.5% with ACE. In the
      presence of noise (at +10 dB signal-to-noise ratio), the mean percent correct
      scores for words were 43.3% with SPEAK compared to 84.4% with ACE; for phrases
      the percentage was 41.1% with SPEAK and 82.2% with ACE. Statistical analysis
      revealed significant improvement in open-set speech recognition with ACE compared
      to SPEAK. Preliminary data suggest that converting children from SPEAK to the ACE
      strategy improves their performance. Subjects showed significant improvements for
      open-set word and sentence recognition in quiet as well as in noise when ACE was
      used in comparison with SPEAK. The greatest improvements were obtained when tests
      were presented in the presence of noise.

PMID- 12049830
TI  - Necrotizing sialometaplasia of parotid gland: a possible vasculitic cause.
AB  - Necrotizing sialometaplasia at the parotid gland location is rare and simulates
      malignant disease. If it is seen at this location, the causes may be previous
      dental or parotid gland surgical procedures, which result in blood vessel
      injuries and thrombosis. We report a parotid gland necrotizing sialometaplasia of
      a 17-year-old girl, possibly caused by primary vascular damage or vasculitis.

PMID- 12049832
TI  - Effect of 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl on
      the induction of hepatic lipid peroxidation and cytochrome P-450 associated
      enzyme activities in rats.
AB  - Polychlorinated biphenyls (PCBs) are environmental contaminants that have been
      widely used for various industrial purposes. In spite of numerous studies on
      PCBs, however, their mechanism of toxicity remains unknown. The role of
      cytochrome P-450 in PCBs induced hepatic lipid peroxidation is controversial.
      Therefore, the present study was undertaken to study the mechanism of action of
      two PCBs and their role in cytochrome P-450 induction and lipid peroxidation,
      determined in vivo and during the incubation of subcellular fractions. We also
      examined whether agonist/antagonist activities between the two PCBs were
      occurring. Two PCBs were studied: 3,3',4,4'-tetrachlorobiphenyl (PCB-77), a non
      ortho-substituted, coplanar PCB; and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153),
      a di-ortho-substituted, non-planar PCB. Groups of male Sprague-Dawley rats were
      given a single i.p. injection of one of the two PCBs (at doses of 30, 150, or 300
      micromol/kg), both PCBs (at doses of 30 or 150 micromol/kg), or vehicle alone.
      Rats were sacrificed after 2, 6, or 24 h; or 2, 6, or 10 days. Cytochrome P-450
      induction occurred as early as 2 h with PCB-77 and 24 h with PCB-153. Significant
      increases in thiobarbituric acid reactive substances (TBARS) content in liver
      tissue occurred 2, 6 and 10 days after treatment with PCB-77 and PCB-153; it was
      unclear whether these PCBs were synergistic in their induction of TBARS
      formation. Liver microsomal fractions incubated with NADPH only showed increased
      TBARS formation at the highest doses of PCB-77 and PCB-153 after 6 days. The
      results indicate that both PCBs induced cytochrome P-450 enzymes and enhanced
      lipid peroxidation in liver and subcellular fractions but with different
      potencies and onsets of action. The results also indicate a larger time
      difference between cytochrome P-450 induction and lipid peroxidation for PCB-77.
      Thus, both PCB-77 and PCB-153 are toxic to cells, but may act via different
      mechanisms to induce their effects.

PMID- 12049831
TI  - Dietary fish oil protects against lung and liver inflammation and fibrosis in
      monocrotaline treated rats.
AB  - The purpose of the present study was to evaluate the effectiveness of fish oil in
      preventing tissue pathologies associated with monocrotaline (MCT) toxicity.
      Twenty-four weanling rats were randomly assigned to one of two groups: (1) 12 to
      a group fed a diet containing 15% (w/w) corn oil (control) and (2) 12 to a group
      fed a diet containing fish oil (13%) and corn oil (2%) as the source of fat. Rats
      were fed for 4 weeks prior to MCT treatment. Six rats in each group were
      subcutaneously injected with MCT and six injected with its vehicle (water) and
      all were continued on their respective diets. All rats were sacrificed 3 weeks
      after injection. In rats receiving MCT, we observed severe interstitial
      pneumonia, septal fibrosis, vasculitis with virtual obliteration of the lumen of
      the small arteries and arterioles, right ventricular hypertrophy (RVH), and
      hepatomegaly and hepatocyte vacuole formation. Dietary fish oil significantly
      reduced septal fibrosis and development of pneumonia. There was a slight, but
      statistically insignificant decrease in vasculitis and fish oil did not prevent
      RVH (pulmonary hypertension). In addition, fish oil effectively protected the MCT
      treated rats from development of hepatocyte vacuoles (steatosis), hepatic
      inflammation and vasculitis, increased presence of fibroblasts and collagen
      deposition in the centrilobular and, to a lesser extent, in the periportal
      spaces. These results suggest that lung parenchymal inflammation can be
      attenuated without altering the course of development of pulmonary hypertension
      in the MCT model. These results also indicate that fish oil protects against
      inflammation and fibrosis in the lung and liver, and against hepatocyte vacuole
      formation in MCT-treated rats.

PMID- 12049833
TI  - Effect of lead on dental enamel formation.
AB  - In this work the effects of lead toxicity on dental enamel formation were
      studied. Epidemiological data and animal studies show an association between lead
      exposure and higher caries prevalence, but the mechanism underlying this
      association is still unknown. Here we present data on enamel formation in rats
      exposed to lead for 70 days in the drinking water. Enamel matrix was used for
      protein analysis and dry weight determination, while mature enamel was used for
      microhardness testing. Enamel matrix was scraped from the teeth and analyzed by
      electrophoresis in bulk or according to developing stage. Increased amounts of
      protein were observed in animals exposed to lead when the same weight of matrix
      was electrophoresed by protein electrophoresis. When extracts were prepared
      according to developing stages, no differences in the amount of protein or band
      pattern were observed. Upper incisors were cut longitudinally for Knoop enamel
      microhardness determination in four regions of the teeth. Microhardness analysis
      revealed statistically significant (P<0.05) decrease in the microhardness values
      of enamel from rats exposed to lead in regions of maturation but not of fully
      mature enamel. These results indicate a delay in enamel mineralization in incisor
      teeth from animals exposed to lead, highlighting a potentially important effect
      of lead toxicity not yet explored.

PMID- 12049834
TI  - Effect of jet fuels on the skin morphology and irritation in hairless rats.
AB  - Jet A and JP-8 are the major jet fuels used in civilian and military (US Air
      Force) flights, respectively. JP-8+100 is a new jet fuel recently introduced by
      US Air Force in some of its locations. The purpose of this study was to
      investigate the effects of dermal exposure of jet fuels (Jet A, JP-8, and JP
      8+100) on the skin morphology, barrier function, moisture content, blood flow,
      and skin irritation (erythema and edema) in hairless rats. Jet fuels were applied
      by both occlusive and unocclusive methods. The skin of treated and control
      (untreated) sites were excised and analyzed by magnetic resonance imaging (MRI)
      (500 MHz, 11.7 Tesla). Unocclusive application of JP-8, Jet A, and JP-8+100
      increased the transepidermal water loss (TEWL) gradually and the values at 120 h
      were significantly greater than the baseline value (P<0.05). Both occlusive and
      unocclusive application of jet fuels decreased the skin moisture content
      significantly (P<0.05). Unocclusive application of JP-8, Jet A, and JP-8+100
      increased the skin blood flow, though the values returned to the baseline levels
      within 24 h. Occlusive application of jet fuels (8 h/day for 2 days) caused a
      substantial increase in the skin blood flow and the values at 48 h were about 6
      fold greater than the baseline value. Occlusive application of jet fuels caused a
      moderate to severe erythema and a moderate edema. MRI was used to obtain proton
      images and water self-diffusion maps of hairless rat skin exposed to jet fuel.
      Exposure to JP-8 showed the largest difference from the control with regards to
      visual observations of the stratum corneum and hair follicles, while JP-8+100
      appeared to affect the hair follicle region. The results of the present study
      demonstrate that exposure to jet fuels can disrupt the skin barrier function,
      cause skin irritation, and alter the skin structure (stratum corneum and viable
      epidermis) and MRI can be used as a tool to investigate the alterations in the
      skin morphology after exposure to toxic chemicals.

PMID- 12049836
TI  - Comparison of low doses of aged and freshly fractured silica on pulmonary
      inflammation and damage in the rat.
AB  - Most previous studies of silica toxicity have used relatively high exposure doses
      of silica. In this study, male rats received by intratracheal instillation either
      vehicle, aged or freshly fractured silica at a dose of either 5 microg/rat once a
      week for 12 weeks (total dose=60 microg) or 20 microg/rat once a week for 12
      weeks (total dose=240 microg). One week after the last exposure, bronchoalveolar
      lavage (BAL) was conducted and markers of pulmonary inflammation, alveolar
      macrophage (AM) activation and pulmonary damage were examined. For rats exposed
      to a total of 60 microg silica, both aged and freshly fractured silica increased
      polymorphonuclear leukocytes (PMN) yield and AM activation above control to a
      similar degree, but no evidence of pulmonary damage, as measured by BAL fluid
      lactate dehydrogenase activity or albumin concentration, was detected. For rats
      exposed to 240 microg silica, aged or freshly fractured silica increased PMN
      yield and AM activation above control. However, zymosan-stimulated and L-NAME
      sensitive AM chemiluminescence was greater for rats exposed to freshly fractured
      silica compared to aged silica. Exposure to 240 microg aged or freshly fractured
      silica also resulted in pulmonary damage, but the extent of this damage did not
      differ between the two types of silica. The results suggest that exposure of rats
      to silica levels far lower than those previously examined can cause pulmonary
      inflammation. In addition, exposure to freshly fractured silica causes greater
      generation of reactive oxygen species from AM, measured as AM chemiluminescence,
      in comparison to aged silica, but there is an apparent threshold below which this
      difference does not occur.

PMID- 12049835
TI  - Evaluation of acute hepatotoxic effects exerted by environmental estrogens
      nonylphenol and 4-octylphenol in immature male rats.
AB  - Nonylphenol (NP) and 4-Octylphenol (4OP) have shown estrogenic properties both in
      vivo and in vitro. Researchers have known for years that estrogens induce a wide
      number of hepatotoxic actions in rodents. In order to study the acute hepatic
      effects exerted by NP and 4OP on rat liver the following endpoints were
      evaluated: relative liver weight (RLW), morphology, cell cycle and ploidy status,
      monooxygenase enzymes content and levels of both, cytosolic estrogen receptor
      (cER) and microsomal binding sites for estrogens (mEBS). Immature male Sprague
      Dawley rats were injected intraperitoneally (i.p.) with 60 mg/kg of NP or 4OP for
      1, 5 or 10 days. Despite the fact that RLW of the animals was not modified but
      any treatment, the histopathological study revealed the presence of an increase
      in the percentage of both, mitotic activity and Ki-67-labeling index (LI) in the
      livers from animals treated with alkylphenols in absence of any degenerative
      lesion. Furthermore, all the livers from alkylphenols-treated groups showed the
      presence of abnormal mitosis and c-mitosis. Although the levels of both, cER and
      cytochrome P450 (Cyt. P450) were not affected by any treatment, concentration of
      the mEBS was decreased after 10 days of treatment with alkylphenols. These
      findings taken together suggest that the exposition to alkylphenols induce cell
      proliferation and spindle disturbances and that these compounds are capable of
      modulating the expression of putative membrane receptors for estrogens.

PMID- 12049837
TI  - Comparative effects of TCDD, endrin, naphthalene and chromium (VI) on oxidative
      stress and tissue damage in the liver and brain tissues of mice.
AB  - The mechanism of toxicity of structurally diverse environmental toxicants
      including heavy metals and polyhalogenated and polycyclic hydrocarbons may
      involve a common cascade of events which entails an oxidative stress and
      production of reactive oxygen species. We have determined the comparative effects
      of single 0.01, 0.10 and 0.50 LD(50) doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD), endrin, naphthalene and sodium dichromate (chromium VI) on lipid
      peroxidation, DNA fragmentation and enhanced production of superoxide anion
      (cytochrome c reduction) in liver and brain tissues of C57BL/6NTac mice. The
      effects of a single acute oral 0.50 LD(50) dose of these xenobiotics on hepatic
      and brain lipid peroxidation were investigated at 0, 12, 24, 48, and 96 h after
      treatment, while the effects of 0.10 LD(50) and 0.01 LD(50) doses of these
      xenobiotics were at 0, 24, 48, 72, and 96 h after treatment. Dose- and time
      dependent effects were observed with all four xenobiotics. At a 0.50 LD(50) dose
      of TCDD, endrin, naphthalene and chromium VI, maximum increases in cytochrome c
      reduction (superoxide anion production) of approximately 5.7-, 5.4-, 5.3- and 4.1
      fold, respectively, were observed in hepatic tissues. TCDD showed an increasing
      effect through 96 h. Endrin and naphthalene demonstrated a maximum effect at 12
      24 h, while chromium VI exhibited a maximum effect at 48 h. With respect to lipid
      peroxidation, at a 0.50 LD(50) dose both endrin and chromium VI induced the
      maximum effect at 48 h of treatment, while naphthalene demonstrated the maximum
      effect after 24 h of treatment. TCDD demonstrated a continued effect through 96 h
      of treatment. At a 0.50 LD(50) dose TCDD, endrin, naphthalene and chromium VI
      produced maximum increases in hepatic lipid peroxidation of approximately 3.5-,
      3.1-, 3.7- and 3.3-fold in hepatic tissues, respectively. Similar results were
      obtained in hepatic and brain DNA fragmentation at 0.50 LD(50) doses. Lesser
      effects were observed with 0.10 and 0.01 LD(50) doses of these xenobiotics as
      compared to the 0.50 LD(50) dose. The results clearly demonstrate that these
      diverse xenobiotics induce dose- and time-dependent oxidative stress and tissue
      damage in the liver and brain tissues of mice.

PMID- 12049839
TI  - Cypermethrin-induced plasma membrane perturbation on erythrocytes from rats:
      reduction of fluidity in the hydrophobic core and in glutathione peroxidase
      activity.
AB  - The effects of treatment with the synthetic insecticide cypermethrin on plasma
      membrane fluidity, lipid peroxidation and antioxidant status in rat erythrocytes
      were investigated. Rats were treated by gavage with a low dose (12.5 mg/kg body
      weight per day) of cypermethrin in corn oil for 60 days. DPH and TMA-DPH
      fluorescence anisotropy experiments show that cypermethrin treatment, compared
      with controls, induced a significant decrease in erythrocyte membrane fluidity
      measured by DPH, while no changes were observed using TMA-DPH. Cypermethrin
      treatment also induced a significant increase in the lipid peroxidation, measured
      by the formation of conjugated dienes. The increased oxidative stress resulted in
      a significant decrease in the activity of glutathione peroxidase. The results are
      discussed in terms of preferential localization of cypermethrin in the
      hydrophobic core of the membrane, where it increases lipid packing and
      consequently decreases membrane fluidity.

PMID- 12049838
TI  - iNOS-null mice are not resistant to cadmium chloride-induced hepatotoxicity.
AB  - Acute administration of cadmium (Cd) to rats results in hepatotoxicity. Recent
      reports indicate that Kupffer cells, the resident macrophages of the liver,
      participate in the manifestation of Cd-induced hepatotoxicity. Nitric oxide (NO)
      is a reactive nitrogen radical produced by activated Kupffer cells via the
      induction of inducible nitric oxide synthase (iNOS). Nitric oxide can combine
      with superoxide to form peroxynitrite, a molecule that may participate in the
      toxic mechanisms of hepatotoxins, such as acetaminophen and bacterial endotoxin.
      It has been speculated that Cd also may exert its hepatotoxicity, in part, via
      the production of NO by iNOS. Therefore, this study was undertaken to determine
      whether iNOS contributes to Cd-induced hepatotoxicity. Wild-type (WT) mice were
      administered selective iNOS inhibitors (AMT and 1400W) concurrently and 3 h after
      administration of a hepatotoxic dose of Cd (4.0 mg Cd/mg). Additionally, WT and
      iNOS-null (iNOS-KO) mice were dosed iv with saline or 2.0, 2.5, 3.0, 3.5 or 4.0
      mg Cd/kg. Serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH)
      activities were quantified to assess liver injury. Administration of iNOS
      inhibitors failed to prevent Cd-induced hepatotoxicity. Also, Cd caused a dose
      dependent increase in liver injury in both WT and iNOS-KO mice. The liver injury
      produced by Cd in the iNOS-KO mice was not different from that in WT at any dose.
      These data indicate that iNOS does not appear to mediate Cd-induced
      hepatotoxicity.

PMID- 12049840
TI  - Lipoic acid increases glutathione production and enhances the effect of mercury
      in human cell lines.
AB  - Thiols are known to influence the metabolism of glutathione. In a previous study
      (Toxicology 156 (2001) 93) dithiothreitol (DTT) did not show any effect on intra-
      or extracellular glutathione concentrations in HeLa cell cultures but increased
      the effects of mercury ions on glutathione concentrations, whereas monothiols
      such as N-acetylcysteine (NAC) or glutathione did not. In the present study, we
      have investigated the effects of thiols as well as the interaction between thiols
      and mercury ions in cultures of both HeLa and hepatoma cells. Furthermore, we
      have added alpha-lipoic acid (LA) to the previously used test panel of thiols,
      since it is metabolised intracellularly to a dithiol (dihydrolipoate). The
      present study shows that LA increased intra- and extracellular concentrations of
      glutathione in both HeLa and hepatoma cell cultures. In contrast to results for
      HeLa cells, the presence of DTT increased the intracellular glutathione
      concentration in hepatoma cells. No increase of glutathione concentrations was
      observed in hepatoma cell cultures in the presence of the monothiols (NAC,
      homocysteine or glutathione) tested, in agreement with previous findings in HeLa
      cell cultures. The presence of dithiols, either DTT or dihydrolipoate (the
      metabolite of LA), increased the effects of mercury ions on glutathione
      concentrations in hepatoma cells, whereas monothiols such as NAC or glutathione
      did not, in agreement with previous findings in HeLa cells. Thus, metabolic
      effects of mercury ions were observed in hepatoma cells as well as in HeLa cells
      at a lower concentration than the supposed toxicity threshold for mercury in
      blood.

PMID- 12049841
TI  - Methylmercury, but not inorganic mercury, causes abnormality of centrosome
      integrity (multiple foci of gamma-tubulin), multipolar spindles and
      multinucleated cells without microtubule disruption in cultured Chinese hamster
      V79 cells.
AB  - Abnormalities of centrosome integrity and spindle organization in the cultured
      Chinese hamster fibroblast cell line V79 exposed to methylmercury (MeHgCl) and
      inorganic mercury (Hg(2+)) were investigated in conjunction with inductions of
      mitotic arrest and multinucleated cells. The centrosome integrity and spindle
      organization were investigated by immunofluorescence of centrosome proteins,
      gamma-tubulin, and beta-tubulin, respectively. MeHgCl at subtoxic concentrations
      caused an increase in mitotic index 6 h after exposure. Ameboid cells with
      multiple pseudopodia were also induced and chromosomes were distributed even in
      the pseudopodia. After the increase in mitotic index caused by MeHgCl,
      multinucleated cells with multiple micronuclei appeared. MeHgCl caused
      abnormality of centrosome integrity (multiple foci of gamma-tubulin) colocalized
      with aberrant spindles in a concentration-dependent manner, while it did not
      cause disruption of centrosome integrity and microtubule organization in
      interphase cells. In addition, MeHgCl led to the appearance of monoastral cells
      with a one-dot signal of gamma-tubulin. By contrast, Hg(2+) did not cause any of
      the changes induced by MeHgCl. Thus, MeHgCl caused centrosome abnormality and the
      related changes without microtubule disruption, suggesting that the mitotic
      centrosome is a critical target for the cytotoxic effects of MeHgCl.

PMID- 12049842
TI  - Microtubule damaging agents induce apoptosis in HL 60 cells and G2/M cell cycle
      arrest in HT 29 cells.
AB  - Microtubule damaging agents (such as paclitaxel and nocodazole (ND)) have been
      used in the clinical cancer chemotherapy. However, the molecular mechanisms of
      these agents in the induction of anti-cancer activity are still unclear. In the
      present study, we demonstrated that 0.2 microM podophyllotoxin (PDP) induced the
      occurrence of apoptosis in human leukemic (HL 60) cells and cell cycle arrest at
      the G2/M phase in HT 29 cells. Our results suggest that the PDP-induced G2/M
      arrest in HT 29 cells was through the intracellular events including (a)
      inhibition of normal mitotic spindle formation, (b) elevation of cyclin B1/cdc2
      kinase activity, (c) concomitant increases in cdc 25 A phosphatase and cdk 7
      kinase activity, and (d) down-regulation of the wee-1 protein expression. On the
      other hand, activations of the caspases 3, 8, and 9, Bcl-2 hyper-phosphorylation,
      and increased leakage of cytochrome c from mitochondria into cytosolic fraction
      were detected in the PDP-treated HL 60 cells. These listed intracellular events
      were interpreted to lead to the apoptosis observed in PDP-treated HL 60 cells. We
      further demonstrated that activation of c-jun N-terminal kinase (JNK) signaling
      pathway may play an important role in the PDP-induced Bcl-2 phosphorylation and
      apoptosis in HL 60 cells as evidenced by the JNK specific anti-sense
      oligonucleotide experiment. Our results demonstrated that the occurrence of
      apoptosis or G2/M cell cycle arrest induced by microtubule damaging agents in
      different cancer cells was through independent mechanisms. The results from the
      present study highlight the molecular mechanisms underlying of the PDP-induced
      anti-cancer activity.

PMID- 12049844
TI  - Interactive dysmorphogenic effects of toxaphene or toxaphene congeners and
      hyperglycemia on cultured whole rat embryos during organogenesis.
AB  - Both diabetes mellitus and exposure to environmental contaminants are becoming
      health hazards to many indigenous populations in the world. In earlier work, we
      established the embryopathy of the chlorinated pesticide, toxaphene technical
      mixture (TOX) and its two physiologically most important congeners, T(2) (2-exo,3
      endo,5-exo,6-endo,8,8,10,10-octachlorobornane) and T(12) (2-exo,3-endo,5-exo,6
      endo,8,8,9,10,10-nonachlorobornane). In this study, the combined effects of
      toxaphene or its two congeners and high glucose concentrations were studied using
      rat embryo culture in order to investigate the potential interactions between
      hyperglycemia and toxaphene exposure. Whole rat embryos (0-2 somite) were
      explanted and cultured into a normal (8 mM) or hyperglycemic 12.5 mM (12.5 G) or
      18.75 mM (18.75 G) culture medium containing TOX, T(2), or T(12) at various
      concentrations (0, 100, 1000, 5000 ng/ml) for 48 h at 37 degrees C. All
      treatments, except mild hyperglycemic exposure (12.5 G), had significant adverse
      effects on the total morphological score, head and crown-rump length, yolk sac
      diameter and yolk sac circulation. Embryos exposed to 18.75 G did not show
      malformations but when hyperglycemia at 18.75 G was combined with higher doses of
      TOX or T(2) synergistic effects on the incidence of neural tube defects were
      observed. The embryos cultured with T(12) under severe hyperglycemic conditions
      of 18.75 G showed an inhibition of T(12)-induced neural tube defects, but there
      was a concurrent underdevelopment of forelimbs or hindlimbs at the highest T(12)
      dose. The results suggest that there is a site-specific and dose-related
      interactive dysmorphogenesis elicited by TOX or its congeners with high levels of
      glucose on rat embryonic development. Because of the relatively high TOX doses
      used in this study, the drastic growth retardation and malformation observed are
      unlikely to be observed in human populations. More subtle effects, however, may
      not be ruled out.

PMID- 12049843
TI  - The effects of haloalkene cysteine conjugates on cytosolic free calcium levels in
      LLC-PK(1) cells--studies utilising digital imaging fluorescence microscopy.
AB  - The aim of this study was to examine the effect of haloalkene S-cysteine
      conjugates on cytosolic free Ca(2+) levels in renal epithelial cells using
      digital imaging fluorescence microscopy (DIFM). S-(1,2,3,4,4-pentachloro-1,3,
      butadienyl)-L-cysteine (PCBC) and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) were
      both cytotoxic to LLC-PK(1) cells in culture. Prior treatment of the cells with
      aminooxyacetic acid (AOAA), an inhibitor of the enzyme cysteine conjugate beta
      lyase, afforded complete protection against the toxicity at concentrations of
      PCBC up to 100 microM and DCVC up to 500 microM. The cytotoxicity produced by
      PCBC (100 microM) was time dependent with no loss of lactate dehydrogenase (LDH)
      into the medium being observed until 4 h after exposure, while removal of calcium
      from the medium prevented the toxicity. Addition of PCBC (100 microM) to LLC
      PK(1) cells produced a small progressive increase in intracellular calcium
      ([Ca(2+)](i)) from 72+/-6 to 126+/-11 nM following 10 min of exposure. At this
      time there was a marked cellular heterogeneity in the calcium response with some
      cells showing marked increases in [Ca(2+)](i), while others cycled between low
      and high values and some just maintained basal levels. Exposure to PCBC (100
      microM) for 1 h produced a more marked increase in [Ca(2+)](I), 469+/-46 nM, with
      all cells responding. The elevation in [Ca(2+)](i) was concentration-related with
      increases seen at concentrations of 5 microM PCBC and above. The increase in
      [Ca(2+)](i) produced by PCBC (100 microM) was prevented by treatment with AOAA,
      and markedly reduced by a nominally calcium free medium or the addition of the
      calcium chelator EGTA. DCVC (500 microM) also markedly elevated [Ca(2+)](i)
      following exposure for 1 h, this was also prevented by AOAA and a nominal calcium
      free medium. These findings indicate that elevation in [Ca(2+)](i) produced by
      PCBC in renal epithelial cells, is an early event in the cascade of signalling
      changes leading to renal cell death. The major source of calcium appears to be
      from increased influx although a small component is released from intracellular
      stores which my trigger a stress protein response.

PMID- 12049845
TI  - Reductive activation of terpenylnaphthoquinones.
AB  - Four terpenylnaphthoquinones were found to enhance the rate of superoxide
      production in the presence of ascorbate as detected from the superoxide dismutase
      (SOD)-inhibitable initial oxygen consumption rates. Initial rates of oxygen
      consumption in the presence of ascorbate plus quinone increase with an increase
      in the half-wave reduction potentials of the quinones. These quinones also
      enhance the rate of Cyt(III)c reduction by xanthine/xanthine oxidase (X/XO) in
      both air- and nitrogen-saturated aqueous solutions at pH 7.4. Maximum rates of
      Cyt(III)c reduction in nitrogen and oxygen-saturated solutions (V(max)), in the
      presence of X/XO, increase with an increase in the half-wave reduction potentials
      of the quinones. SOD inhibits Cyt(III)c reduction rates in the presence of these
      quinones and X/XO in a manner which is also dependent on the quinone half-wave
      redox potential. The relative antineoplastic activity of two of these quinones
      follows the order in rates of oxygen consumption or Cyt(III)c reduction. This is
      consistent with an antineoplastic action of these quinones through the mechanism
      of redox cycling or possible interference or inhibition of mitochondrial
      respiration.

PMID- 12049846
TI  - Chronic toxicity and oncogenicity study with glutaraldehyde dosed in the drinking
      water of Fischer 344 rats.
AB  - Glutaraldehyde (GA) has a wide spectrum of industrial, scientific and biomedical
      applications. Its potential to produce chronic toxic and/or oncogenic effects was
      investigated in Fischer 344 rats (100/sex/group) given GA in drinking water for a
      maximum of 104 weeks. GA concentrations were 0 (control), 50,250 and 1000 ppm,
      resulting in average daily GA consumptions, respectively, of 0, 4, 17 and 64
      mg/kg for males and 0, 6, 25 and 86 mg/kg for females. Interim euthanasia
      (10/sex/group) was performed at 52 and 78 weeks. Parameters evaluated were
      clinical signs, body weight, food and water consumption, hematology, serum
      chemistry, urinalysis, organ weights, gross and microscopic pathology. There were
      no treatment-related effects on mortality. Absolute body weights and body weight
      gains of the 250 and 1000 ppm males and females were reduced over the study in a
      dosage-related manner. Food and water consumption by the 250 and 1000 ppm groups
      were decreased in a statistically significant dose-related manner over the study,
      and mean water consumption by the 50 ppm animals was slightly reduced but not
      with statistical significance. The 250 and 1000 ppm groups had a dose-related
      decrease in urine volume with increased osmolality, and pH was slightly reduced.
      Absolute kidney weights were increased in the 250 and 1000 ppm groups at the 52
      and 78 week sacrifices, and decreased at 104 weeks. Relative kidney weights were
      increased at all sacrifice times for the 1000 ppm group, at 52 weeks for the 250
      ppm group, and at 72 weeks for the 50 ppm group. The urinalysis and renal weight
      changes are compatible with a physiological compensatory adaptation to reduced
      water consumption. Gross and histological evidence for gastric irritation was
      observed principally in the 1000 ppm rats euthanized at 104 weeks and in animals
      that died during the study. Bone marrow hyperplasia and renal tubular
      pigmentation, seen in rats that died and the 104 week euthanasia animals, may
      have been secondary to a low grade hemolytic anemia in animals with large
      granular lymphocytic leukemia (LGLL). The only neoplasm that showed a
      statistically significant increase was LGLL, which occurred at a high incidence
      in both sexes and all groups, including the controls, for both animals that died
      and at the 104 week euthanasia. A few instances of LGLL were observed at 78
      weeks. The overall incidence of LGLL in the spleen for the 0, 50, 250 and 1000
      ppm groups was, respectively, 43, 51, 40 and 46% for males, and 24, 41, 41 and
      53% for females. Statistical analyses indicated that the severity of LGLL was
      associated with the higher dosages of GA in female, but not male, rats. Due to
      the background and variable incidence of LGLL in the Fischer 344 rat, the finding
      of a statistical significance only for female rats, and because, there was no
      clear dose-response relationship, the biological significance of the LGLL
      findings is unclear. There is the possibility that the significance was a
      statistical artifact due to the low incidence of LGLL in the female control
      animals as a result of biological variability within the study. It is also
      considered to be possible that the chronic dosage of GA in the drinking water
      resulted in a modification of one or more of the factors responsible for the
      expression of this common and spontaneously occurring neoplasm in the Fischer 344
      rat.

PMID- 12049847
TI  - Organotin-induced apoptosis occurs in small CD4(+)CD8(+) thymocytes and is
      accompanied by an increase in RNA synthesis.
AB  - The organotin compounds di-n-butyltin dichloride (DBTC) and tri-n-butyltin
      chloride (TBTC) induce thymus atrophy in rats. At low doses they inhibit immature
      thymocyte proliferation, whereas at higher doses in particular TBTC induces
      apoptotic cell death. In vitro, a similar concentration-effect relationship was
      observed, i.e. low concentrations inhibit DNA and protein synthesis and higher
      concentrations induce apoptosis. The mechanism of apoptosis by organotins has
      been partly investigated, but their capacity to inhibit protein synthesis seems
      to contradict with the idea that macromolecular synthesis is required for
      organotin-induced apoptosis. Therefore, we aimed to evaluate the relation between
      apoptosis and the synthesis of RNA and proteins, with a focus on the apoptosis
      sensitive thymocyte subset. Results showed that DBTC increases RNA synthesis in
      particular in the subset of small CD4(+)CD8(+) thymocytes, which normally shows a
      high incidence of DNA fragmentation. Moreover, the RNA synthesis inhibitor
      actinomycin D or the protein synthesis inhibitor cycloheximide protected cells
      from apoptosis by DBTC or TBTC. Although organotin compounds increase synthesis
      of the heat shock protein HSC73/HSP72, heat shock treatment did not initiate
      apoptosis in thymocytes, neither antagonized organotin-induced apoptosis. This
      indicates that synthesis of heat shock proteins is not related to organotin
      induced increase of RNA synthesis, and that other RNA-molecules are probably
      involved.

PMID- 12049848
TI  - Impact of protein binding on the availability and cytotoxic potency of
      organochlorine pesticides and chlorophenols in vitro.
AB  - In vitro toxicity data are generally based on nominal concentrations and thus
      depend on both activity and availability of a compound. The aims of the present
      study were to examine the influence of protein binding on the cytotoxicity of
      selected organochlorine pesticides and chlorophenols in Balb/c 3T3 cell cultures
      and to determine parameters of protein binding which can be used to estimate
      protein bound fractions and to model distribution in vitro. EC(50)-values derived
      from concentration-effect relationships determined in the presence of various
      concentrations of bovine serum albumin (BSA) were linearly correlated to BSA
      concentration. Increasing the BSA concentration from about 1.2 to 40 mg/ml
      increased the EC(50)-values by factors between 3.4 and 34.4. Molar ratios of
      substance bound to albumin ranged from 0.11 to 2.42. Calculated fractions bound
      to albumin in the normal growth medium were 0.075-0.17 (p,p'-DDT, p,p'-DDE,
      dieldrin, lindane), 0.09-0.1 (4-mono- and 2,4-dichlorophenol), 0.68 (2,4,5
      trichlorphenol) and almost 1.0 (pentachlorophenol). At 40 mg/ml BSA any compound
      was largely bound to albumin (fractions bound > or = 0.74). Distribution
      modelling revealed that the availability of the highly hydrophobic
      organochlorines additionally was significantly reduced by partitioning into
      lipids. The results clearly demonstrate that nominal and relative toxic potencies
      of organochlorine pesticides and chlorophenols determined in vitro are
      substantially influenced by effects of protein binding on availability.

PMID- 12049849
TI  - Maternal-to-fetus transfer of mercury in metallothionein-null pregnant mice after
      exposure to mercury vapor.
AB  - This study examined the role of placenta metallothionein (MT) in maternal-to
      fetal mercury transfer in MT-null and wild-type mice after exposure to elemental
      mercury (Hg(0)) vapor. Both strains were exposed to Hg(0) vapor at 5.5-6.7
      mg/m(3) for 3 h during late gestation. Twenty-four hours after exposure to Hg(0)
      vapor, accumulation of mercury in the major organs, except the brain, of MT-null
      maternal mice was significantly lower than that in organs of wild-type mice. In
      contrast to mercury levels in maternal organs, fetal mercury levels were
      significantly higher in MT-null mice than in wild-type mice. In placenta, mercury
      concentrations were not significantly different between the two strains. Although
      MT levels in major organs, except the brain, of wild type mice were markedly
      elevated after the exposure to Hg(0) vapor, the placental MT levels were not
      elevated. However, endogenous MT level in the placenta is significantly higher
      than that in other organs, except the liver. Gel filtration profile of the
      placental cytosol in the wild-type mice revealed that a large amount of placental
      mercury was associated with MT. In MT-null mice, mercury in placental cytosol
      appeared mainly in the high-molecular-weight protein fractions. Mercury in the
      placenta was localized mainly in the yolk sac and decidual cells in the deep
      layer of the decidua in both mouse strains. The similar localization of MT was
      found in the placenta of wild type mice. These results suggest that MT in the
      placenta has a defensive role in preventing maternal-to-fetal mercury transfer.

PMID- 12049850
TI  - Dietary zinc deficiency induced-changes in the activity of enzymes and the levels
      of free radicals, lipids and protein electrophoretic behavior in growing rats.
AB  - Zinc (Zn) is an essential nutrient that is required in humans and animals for
      many physiological functions, including immune and antioxidant function, growth
      and reproduction. The present study was conducted to investigate the effects of
      adequate Zn level (38 mg/kg diet, as a control) and two low levels that create Zn
      deficiencies (19 mg/kg diet, 1/2 of the control and 3.8 mg/kg diet, 1/10 of the
      control) in growing male and female rats for 10 weeks. To evaluate the effects of
      these levels, the concentrations of thiobarbituric acid-reactive substances
      (TBARS), biochemical parameters and protein pattern were studied. Lipid
      peroxidation in liver, brain and testes of rats fed Zn-deficient diet was
      indicated by increased TBARS. Serum, liver, brain and testes glutathione S
      transferase (GST) activities were significantly (P<0.05) increased in Zn
      deficient rats, the effect was pronounced in rats fed the lowest level of Zn
      (1/10 of control). The activity of lactate dehydrogenase (LDH) was significantly
      (P<0.05) increased in liver, brain and testes, but decreased in serum in a dose
      dependent manner. Zinc deficiency increased (P<0.05) liver aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) activities in a dose
      dependent manner, while there was no effect on the activity of these enzymes in
      testes. Zinc deficiency resulted in a significant (P<0.05) decrease in the
      activity of alkaline phosphatase (AlP) in serum and liver in a dose-dependent
      manner, but no effect in testes was found. The activity of acid phosphatase (AcP)
      was not affected in serum, liver and testes. Zn-deficient rats had higher liver
      concentrations of total lipids (TL), cholesterol, triglyceride (TG), and low
      density lipoprotein (LDL), while high density lipoprotein (HDL) was significantly
      (P<0.05) declined in a dose-dependent manner. Brain and serum
      acetylcholinesterase (AChE) activities were, however, not affected (P<0.05) by Zn
      deficiency. Protein content in liver, brain and testes showed a significant
      (P<0.05) decrease in rats fed the lowest level of Zn (1/10 of control).
      Polyacrylamide gel electrophoresis (native-PAGE) of serum proteins revealed that
      the intensity of immunoglobulins, serum albumin as well as several peptide bands
      were decreased in rats fed 1/2 or 1/10 of Zn adequate, i.e. their synthesis was
      affected and it was pronounced with the lowest level of Zn deficiency (1/10 of
      control). However, no clear effect on the transferrin was observed in both cases
      compared to controls. From the results of this study it can be concluded that Zn
      deficiency exerts numerous alterations in the studied biochemical parameters,
      protein pattern, and increased lipid peroxidation.

PMID- 12049851
TI  - Immunomodulatory effects of high-dose alpha-tocopherol acetate on mice subjected
      to sidestream cigarette smoke.
AB  - Several recent epidemiological investigations raise serious questions about the
      health effects of high-dose supplements of Vitamin E (VE) in cigarette smokers.
      To examine these findings, a total of 96 C57BL/6 mice were randomly assigned to
      eight groups in a 2 x 4 factorial design (smoke vs. sham smoke and normal diet
      vs. 3 VE supplements). The mice were exposed to sidestream cigarette smoke
      (SSCS), at 0.4 mg total particulate matter/m(3) air, from standard research
      cigarettes (1R4)/day or filtered room air at 30 min/day, 5 days/week, for 9 weeks
      through a nose-only exposure chamber. The American Institute of Nutrition 93G
      purified rodent diet was modulated with 75 (regular diet, 1-fold), 1050 (15
      fold), 5550 (75-fold), and 11175 (150-fold) IU dl-alpha-tocopherol acetate (alpha
      TA)/kg as VE supplementation and provided ad libitum at an average intake rate of
      4.11 g diet/mouse/day. This result demonstrated that SSCS exposure results in
      lung dysfunction, as indicated by a decrease of pulmonary dynamic compliance
      (C(dyn)) and increase of lung resistance (R(L)), and body weight loss in mice fed
      with regular diet. These changes accompanied with increases of bronchoalveolar
      lavage (BAL) concentrations of cytokines interleukin (IL)-1 beta, IL-4 and IFN
      gamma, as well as hepatic lipid peroxidation. However, supplemental alpha-TA at
      the doses of > or = 1050 IU/kg diet prevented the SSCS-induced body weight loss
      and lung dysfunction. alpha-TA at > or = 5550 IU/kg significantly increased BAL
      levels of IL-2 and IL-4 in both the sham SSCS and the SSCS groups. Given at 5550
      IU alpha-TA/kg, but not higher, mice elevated BAL IL-1 beta level if they were
      exposed to SSCS. Hepatic lipid peroxidation was decreased in a dose-dependent
      fashion with different alpha-TA supplements in both the sham SSCS and SSCS
      groups. Neither SSCS nor alpha-TA had an effect on lung permeability, BAL IL-6,
      splenic T and B lymphocyte proliferation and their T helper (Th)1 and Th2
      cytokines measured among all groups. Data suggest that supplemental alpha-TA may
      be needed to counteract SSCS-induced oxidative stress, but that potential side
      effects introduced by high dosage of this synthetic compound should be
      considered.

PMID- 12049852
TI  - Calcium supplementation during lactation blunts erythrocyte lead levels and delta
      aminolevulinic acid dehydratase zinc-reactivation in women non-exposed to lead
      and with marginal calcium intakes.
AB  - The purpose of this study was to evaluate the effect of calcium supplementation
      during lactation on changes in blood lead indices from late pregnancy to early
      lactation in women with low calcium intakes and low lead-exposure. Forty-seven
      women, non-occupationally exposed to lead and with habitually low calcium intake
      ( approximately 600 mg/d), participated in the study from 29 to 38 weeks of
      pregnancy to 7-8 weeks post-partum, non-supplemented (n=25) and supplemented
      (n=22) with calcium (500 mg/d) during 6 weeks after delivery. Erythrocyte lead
      (PbRBC) and in vitro reactivation with zinc of blood delta-aminolevulinic acid
      dehydratase (Zn-delta-ALAD% reactivation) were used as lead indices. In the non
      supplemented group, PbRBC and Zn-delta-ALAD% reactivation increased significantly
      (P<0.001) from pregnancy (0.202+/-0.049 microg Pb/g protein and 18.3+/-6.0%) to
      lactation (0.272+/-0.070 microg Pb/g protein and 22.7+/-6.2%). No significant
      changes of these indices were observed in the calcium-supplemented group from
      pregnancy (0.203+/-0.080 microg Pb/g protein and 15.8+/-4.5%) to lactation
      (0.214+/-0.066 microg Pb/g protein and 16.3+/-4.1%). PbRBC levels and Zn-delta
      ALAD% reactivation at lactation were lower (P<0.05) and hematocrit levels were
      higher (P<0.05) in the calcium-supplemented compared to the non-supplemented
      women. Calcium supplementation during lactation appears to blunt the lactation
      induced increase in maternal blood lead and its inhibitory effect on delta-ALAD
      and possibly on maternal erythropoiesis.

PMID- 12049853
TI  - Europe on the brink of direct-to-consumer drug advertising.

PMID- 12049854
TI  - Fondaparinux: a new synthetic pentasaccharide for thrombosis prevention.

PMID- 12049855
TI  - Cytokeratin 7/20 immunostaining: Barrett's oesophagus or gastric intestinal
      metaplasia?

PMID- 12049856
TI  - The UK blood transfusion service: over a (patent) barrel?

PMID- 12049857
TI  - Osteoporosis--the disease of the 21st century?

PMID- 12049858
TI  - Postoperative fondaparinux versus preoperative enoxaparin for prevention of
      venous thromboembolism in elective hip-replacement surgery: a randomised double
      blind comparison.
AB  - BACKGROUND: Despite use of thromboprophylaxis, elective hip-replacement surgery
      carries a high risk of venous thromboembolic complications. We aimed to assess
      the ability of the pentasaccharide fondaparinux, the first of a new class of
      synthetic antithrombotic agents, to further reduce this risk. METHODS: In a
      double-blind study, we randomly assigned 2309 consecutive patients aged 18 years
      or older who were undergoing elective hip-replacement surgery to once daily,
      subcutaneous injections of either 2.5 mg fondaparinux, starting postoperatively,
      or 40 mg enoxaparin, starting preoperatively. The primary efficacy outcome was
      venous thromboembolism up to day 11, defined as deep-vein thrombosis detected by
      mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or
      documented symptomatic pulmonary embolism. The main safety outcomes were bleeding
      and death. The duration of follow-up was 6 weeks. Analysis was per protocol.
      FINDINGS: We assessed the primary efficacy outcome in 1827 (79%) of 2309
      patients. By day 11, venous thromboembolisms were recorded in 37 (4%) of 908
      patients assigned to fondaparinux and in 85 (9%) of 919 assigned to enoxaparin
      (difference -5.2% [95% CI -8.1 to -2.7], p<0.0001). The relative reduction in
      risk was 55.9% (95% CI 33.1-72.8). The two groups did not differ in frequency of
      death or clinically relevant bleeding. INTERPRETATION: Drugs that act through
      specific inhibition of factor Xa, such as fondaparinux, could be more effective
      than low molecular weight heparins in prevention of venous thromboembolism in
      patients undergoing hip-replacement surgery.

PMID- 12049859
TI  - A goose named Lindholm.

PMID- 12049860
TI  - Postoperative fondaparinux versus postoperative enoxaparin for prevention of
      venous thromboembolism after elective hip-replacement surgery: a randomised
      double-blind trial.
AB  - BACKGROUND: Elective hip-replacement surgery carries significant risk of venous
      thromboembolism, despite use of thromboprophylaxis. We aimed to see whether the
      pentasaccharide fondaparinux, the first drug of a new class of synthetic
      antithrombotic agents, could reduce this risk to a greater extent than other
      available treatments. METHODS: In a double-blind study, we randomly assigned 2275
      consecutive patients aged 18 years or older who were undergoing elective hip
      replacement surgery to receive postoperative subcutaneous injections of either
      2.5 mg fondaparinux once daily or 30 mg enoxaparin twice daily. The primary
      efficacy outcome was venous thromboembolism to day 11. The main safety outcomes
      were bleeding and death. Patients were followed up for 6 weeks. FINDINGS: We
      assessed venous thromboembolism to day 11 in 1584 (70%) of 2275 patients. By day
      11, venous thromboembolisms were recorded in 48 (6%) of 787 patients on
      fondaparinux and in 66 (8%) of 797 patients on enoxaparin. The relative reduction
      in risk was 26.3% (95% CI -10.8 to 52.8, p=0.099). The two groups did not differ
      in the number of patients who died or in the number who had clinically relevant
      bleeding. INTERPRETATION: In patients undergoing elective hip-replacement
      surgery, 2.5 mg fondaparinux once daily was not significantly more effective than
      30 mg enoxaparin twice daily in reducing risk of venous thromboembolism. However,
      the lower risk recorded with fondaparinux than enoxaparin was clinically
      important, with no increase in clinically relevant bleeding.

PMID- 12049861
TI  - Surgical resection with or without preoperative chemotherapy in oesophageal
      cancer: a randomised controlled trial.
AB  - BACKGROUND: The outlook for patients with oesophageal cancer undergoing surgical
      resection with curative intent is poor. We aimed to assess the effects of
      preoperative chemotherapy on survival, dysphagia, and performance status in this
      group of patients. METHODS: 802 previously untreated patients with resectable
      oesophageal cancer of any cell type were randomly allocated either two 4-day
      cycles, 3 weeks apart, of cisplatin 80 mg/m(2) by infusion over 4 h plus
      fluorouracil 1000 mg/m(2) daily by continuous infusion for 4 days followed by
      surgical resection (CS group, n=400), or resection alone (S group, 402).
      Clinicians could choose to give preoperative radiotherapy to all their patients
      irrespective of randomisation. Primary outcome measure was survival time.
      Analysis was by intention to treat. FINDINGS: No patients dropped out of the
      study. Resection was microscopically complete in 233 (60%) of 390 assessable CS
      patients and 215 (54%) of 397 S patients (p<0.0001). Postoperative complications
      were reported in 146 (41%) CS and 161 (42%) S patients. Overall survival was
      better in the CS group (hazard ratio 0.79; 95% CI 0.67-0.93; p=0.004). Median
      survival was 512 days (16.8 months) in the CS group compared with 405 days (13.3
      months) in the S group (difference 107 days; 95% CI 30-196), and 2-year survival
      rates were 43% and 34% (difference 9%; 3-14). INTERPRETATION: Two cycles of
      preoperative cisplatin and fluorouracil improve survival without additional
      serious adverse events in the treatment of patients with resectable oesophageal
      cancer.

PMID- 12049863
TI  - Patellar metastasis.

PMID- 12049862
TI  - Arterial embolisation or chemoembolisation versus symptomatic treatment in
      patients with unresectable hepatocellular carcinoma: a randomised controlled
      trial.
AB  - BACKGROUND: There is no standard treatment for unresectable hepatocellular
      carcinoma. Arterial embolisation is widely used, but evidence of survival
      benefits is lacking. METHODS: We did a randomised controlled trial in patients
      with unresectable hepatocellular carcinoma not suitable for curative treatment,
      of Child-Pugh class A or B and Okuda stage I or II, to assess the survival
      benefits of regularly repeated arterial embolisation (gelatin sponge) or
      chemoembolisation (gelatin sponge plus doxorubicin) compared with conservative
      treatment. 903 patients were assessed, and 112 (12%) patients were finally
      included in the study. The primary endpoint was survival. Analyses were by
      intention to treat. FINDINGS: The trial was stopped when the ninth sequential
      inspection showed that chemoembolisation had survival benefits compared with
      conservative treatment (hazard ratio of death 0.47 [95% CI 0.25-0.91], p=0.025).
      25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolisation, and
      25 of 35 assigned conservative treatment died. Survival probabilities at 1 year
      and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolisation,
      and 63% and 27% for control (chemoembolisation vs control p=0.009).
      Chemoembolisation induced objective responses sustained for at least 6 months in
      35% (14)of cases, and was associated with a significantly lower rate of portal
      vein invasion than conservative treatment. Treatment allocation was the only
      variable independently related to survival (odds ratio 0.45 [95% CI 0.25-0.81],
      p=0.02). INTERPRETATION: Chemoembolisation improved survival of stringently
      selected patients with unresectable hepatocellular carcinoma.

PMID- 12049864
TI  - Circulating concentrations of insulin-like growth factor-I and development of
      glucose intolerance: a prospective observational study.
AB  - BACKGROUND: Results of experimental and clinical studies suggest that insulin
      like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) could be
      important determinants of glucose homoeostasis. However, experimental models
      might also reflect compensatory and adaptive metabolic processes. We therefore
      prospectively examined the associations between circulating concentrations of IGF
      I and IGFBP-1 and development of glucose tolerance. METHODS: Participants in this
      cohort study were a random sample of 615 normoglycaemic men and women aged 45-65
      years. Participants underwent oral glucose tolerance testing based on WHO
      definitions and criteria in 1990-92 and 1994-96. At the baseline visit, we
      measured serum concentrations of IGF-I and IGFBP-1, and assessed the relation
      between these peptides and subsequent glucose intolerance. FINDINGS: At 4.5 years
      of follow-up, 51 (8%) of 615 participants developed impaired glucose tolerance or
      type-2 diabetes. After adjustment for correlates of IGF-I and risk factors for
      glucose intolerance, the odds ratio for risk of impaired glucose tolerance or
      type-2 diabetes for participants with IGF-I concentrations above the median (> or
      = 152 microg/L) compared with those with concentrations below the median (<152
      microg/L) was 0.50 (0.26-0.95). Consistent with this finding, IGF-I also showed a
      significant inverse association with subsequent 2-h glucose concentrations, which
      was independent of correlates of IGF-I and risk factors for glucose tolerance (p
      for linear trend=0.026). We also found that this inverse association was
      independently modified by IGFBP-1 (p for interaction=0.011). INTERPRETATION:
      These data show that circulating IGF-I and its interaction with IGFBP-1 could be
      important determinants of glucose homoeostasis and provide further evidence for
      the possible protective role of IGF-I against development of glucose intolerance.

PMID- 12049865
TI  - Fever and anasarca.

PMID- 12049866
TI  - Preoperative haemoglobin concentration and mortality rate after coronary artery
      bypass surgery.
AB  - We did an observational study in 2059 patients undergoing coronary artery bypass
      surgery to assess the effect of haemoglobin concentration on in-hospital
      mortality. We noted that individuals with a preoperative haemoglobin
      concentration of 100 g/L or less had a five-fold higher in-hospital mortality
      rate after surgery than those with a higher haemoglobin concentration, despite
      having had blood transfusions or the pump primed with blood preoperatively as a
      routine precaution. Our findings suggest that a low haemoglobin concentration is
      a marker of disease severity or comorbidity that has a major effect on survival
      rate.

PMID- 12049867
TI  - Diffusion tensor imaging in refractory epilepsy.
AB  - Diffusion tensor imaging is an imaging method that is sensitive to the molecular
      movement of water, which indicates cellular integrity and pathology. A patient
      with refractory epilepsy and normal conventional MRI was examined with diffusion
      tensor imaging. An area of abnormal diffusion in the right frontal lobe was
      identified and surgically resected. The patient had a good clinical outcome.
      Histopathological examination of the resected tissue showed gliosis. Our findings
      may affect the investigation of similar patients, and provide histopathological
      confirmation of diffusion abnormalities.

PMID- 12049868
TI  - Cerebral oedema as a possible complication of treatment with imatinib.
AB  - Imatinib is a potent drug used in treatment of chronic myeloid leukaemia (CML).
      It acts by inhibition of the CML-specific p210 BCR-ABL tyrosine kinase, but also
      blocks other pathways such as platelet-derived growth factor (PDGF) and c-kit
      receptor signalling. Clinical trials have confirmed the efficacy of imatinib,
      which has toxic effects in cells that express BCR-ABL. Side-effects, although
      frequent, are generally mild and include superficial oedema and fluid retention.
      Here, we describe two patients with cerebral oedema, which in one patient was
      fatal. The pathophysiological mechanisms remain unknown, although the drug could
      act through inhibition of the PDGF receptor.

PMID- 12049869
TI  - UN conference on children bows to US pressure.

PMID- 12049870
TI  - Obstructive sleep apnoea in children might impair cognition and behaviour.

PMID- 12049874
TI  - East Africa to tackle high rates of child prostitution.

PMID- 12049875
TI  - New US restrictions on foreign students.

PMID- 12049876
TI  - Brundtland sets out priorities at annual World Health Assembly.

PMID- 12049877
TI  - Uruguayan health care starts to feel impact of Argentina's collapse.

PMID- 12049878
TI  - Lawsuit targets US resident matching programme.

PMID- 12049880
TI  - Traditional medicine gets healthy recognition.

PMID- 12049882
TI  - Epidemiology and outcomes of osteoporotic fractures.
AB  - Bone mass declines and the risk of fractures increases as people age, especially
      as women pass through the menopause. Hip fractures, the most serious outcome of
      osteoporosis, are becoming more frequent than before because the world's
      population is ageing and because the frequency of hip fractures is increasing by
      1-3% per year in most areas of the world. Rates of hip fracture vary more widely
      from region to region than does the prevalence of vertebral fractures. Low bone
      density and previous fractures are risk factors for almost all types of fracture,
      but each type of fracture also has its own unique risk factors. Prevention of
      fractures with drugs could potentially be as expensive as medical treatment of
      fractures. Therefore, epidemiological research should be done and used to
      identify individuals at high-risk of disabling fractures, thereby allowing
      careful allocation of expensive treatments to individuals most in need.

PMID- 12049883
TI  - St Anthony's fire and living ligatures: a short history of ergometrine.

PMID- 12049884
TI  - Choosing the method to match the perspective: economic assessment and its
      implications for health-services efficiency.

PMID- 12049885
TI  - How tainted is medicine?

PMID- 12049886
TI  - How tainted is medicine?

PMID- 12049887
TI  - How tainted is medicine?

PMID- 12049888
TI  - How tainted is medicine?

PMID- 12049889
TI  - Shunts in unexplained psychotic reactions and encephalopathy.

PMID- 12049890
TI  - Decrease of resistance to imatinib in leukaemia.

PMID- 12049891
TI  - Decrease of resistance to imatinib in leukaemia.

PMID- 12049894
TI  - Distribution of salivary aquaporin-5 in Sjogren's syndrome.

PMID- 12049892
TI  - Distribution of salivary aquaporin-5 in Sjogren's syndrome.

PMID- 12049895
TI  - Life-threatening anaphylaxis after artificial insemination.

PMID- 12049896
TI  - SEN viruses and treatment response in chronic hepatitis C virus.

PMID- 12049898
TI  - SEN viruses and treatment response in chronic hepatitis C virus.

PMID- 12049899
TI  - Malaria rapid tests: a public health perspective.

PMID- 12049900
TI  - Cost of inhaled nitric oxide therapy in neonates.

PMID- 12049901
TI  - Violence and internally displaced women and adolescent girls.

PMID- 12049902
TI  - HIV/AIDS data in South Africa.

PMID- 12049905
TI  - Tools of the trade: the Finsen Light.

PMID- 12049913
TI  - A new dawn for plant mitochondrial NAD(P)H dehydrogenases.

PMID- 12049914
TI  - Probing the dynamics of photosynthetic membranes with fluorescence recovery after
      photobleaching.
AB  - In the past few years, there has been remarkable progress in knowledge of the
      structures and organization of the protein complexes of photosynthetic membranes.
      However, static structures do not tell the whole story. Photosynthetic membranes,
      like other biological membranes, are dynamic systems. Recent technological
      advances are making it increasingly easy to probe the dynamics of photosynthetic
      membranes using fluorescence recovery after photobleaching. Here we explain the
      potential and the limitations of the technique.

PMID- 12049919
TI  - Higher plants contain a modified cytochrome c(6).

PMID- 12049920
TI  - Hydrogenases in green algae: do they save the algae's life and solve our energy
      problems?
AB  - Green algae are the only known eukaryotes with both oxygenic photosynthesis and a
      hydrogen metabolism. Recent physiological and genetic discoveries indicate a
      close connection between these metabolic pathways. The anaerobically inducible
      hydA genes of algae encode a special type of highly active [Fe]-hydrogenase.
      Electrons from reducing equivalents generated during fermentation enter the
      photosynthetic electron transport chain via the plastoquinone pool. They are
      transferred to the hydrogenase by photosystem I and ferredoxin. Thus, the [Fe]
      hydrogenase is an electron 'valve' that enables the algae to survive under
      anaerobic conditions. During sulfur deprivation, illuminated algal cultures
      evolve large quantities of hydrogen gas, and this promises to be an alternative
      future energy source.

PMID- 12049921
TI  - Flagellin perception: a paradigm for innate immunity.
AB  - There are surprising similarities between how animals and plants perceive
      pathogens. In animals, innate immunity is based on the recognition of pathogen
      associated molecular patterns. This is mediated by the Toll-like receptor (TLR)
      family, which rapidly induce the innate immunity response, a first line of
      defence against infectious disease. Plants have highly sensitive perception
      systems for general elicitors and they respond to these stimuli with a defence
      response. One of these general elicitors is flagellin, the main component of the
      bacterial flagellum. Genetic analysis in Arabidopsis has shown that FLS2, which
      encodes a receptor-like kinase, is essential for flagellin perception. FLS2
      shares homology with the TLR family, and TLR5 is responsible for flagellin
      perception in mammals.

PMID- 12049922
TI  - Peptide transport in plants.
AB  - Recent completion of the Arabidopsis genome revealed that this organism has ten
      times more peptide transporters than any other sequenced organism (prokaryote or
      eukaryote). These transporters are found in three protein families: the ABC-type
      transporters; the di- and tripeptide transporters; and the newly described tetra-
      and pentapeptide oligopetide transporters. The abundance of these transporters
      suggests that they play diverse and important roles in plant growth and
      development. Possible substrates for these transporters include glutathione,
      gamma-glutamyl peptides, hormone-amino acid conjugates, phytosulfokine, peptide
      like compounds and peptide phytotoxins. However, the exact role of peptide
      transport in plants is still undefined.

PMID- 12049924
TI  - Pollination failure in plants: why it happens and when it matters.
AB  - Pollination is the primary step in seed formation. Pollination biologists have
      shown that pollination failure can occur at all steps in the dispersal process
      and at several different levels. Increased risk of pollination failure is
      associated with pollen if it is delivered to a stigma too little, too much, too
      late, too mixed in composition or too poor in quality. It is associated with
      pollinators when they are too few or too inconstant, and with plants when they
      are too specialized or too selective. It is associated with populations when they
      are too sparse, too small in number or too uniform genetically, and with
      communities when they are too fragmented, genetically impoverished or under rapid
      modification. Understanding the causes of pollination failure in plants can aid
      the successful conservation and recovery of rare plants, maintenance of crop
      yields, and sustainable use of wild plant resources such as forest timber.

PMID- 12049923
TI  - Glucosinolate research in the Arabidopsis era.
AB  - The wide range of biological activities of products derived from the
      glucosinolate-myrosinase system is biologically and economically important. On
      the one hand, the degradation products of glucosinolates play an important role
      in the defence of plants against herbivores. On the other hand, these compounds
      have toxic (e.g. goitrogenic) as well as protective (e.g. cancer-preventing)
      effects in higher animals and humans. There is a strong interest in the ability
      to regulate and optimize the levels of individual glucosinolates tissue
      specifically to improve the nutritional value and pest resistance of crops.
      Recent advances in our understanding of glucosinolate biosynthesis have brought
      us closer to this goal.

PMID- 12049925
TI  - Recollections and reflections of a plant physiologist.

PMID- 12049926
TI  - Digestion and absorption of food in plants: a plant stomach.

PMID- 12049929
TI  - Molecular mechanisms controlling cortical gliogenesis.
AB  - The sequential appearance of neurons and glia in the vertebrate central nervous
      system may be governed by competition between growth factor signaling pathways
      and downstream transcription factors. In cortical progenitor cell cultures, the
      proneural basic helix-loop-helix transcription factor Ngn1 suppresses formation
      of astrocytes by sequestering coactivator proteins that are required by signal
      transducers and activators of transcription for the expression of astrocyte
      specific genes. In the developing neural tube, combinatorial interactions between
      the proneural transcription factor Ngn2 and the basic helix-loop-helix
      transcription factor Olig2 specify the formation of motor neurons or
      oligodendrocytes.

PMID- 12049930
TI  - Axon guidance: receptor complexes and signaling mechanisms.
AB  - The generation of a functional neuronal network requires that axons navigate
      precisely to their appropriate targets. Molecules that specify guidance decisions
      have been identified, and the signaling events that occur downstream of guidance
      receptors are beginning to be understood. New research shows that guidance
      receptor signaling can be hierarchical -- one receptor silencing the other --
      thereby allowing navigating growth cones to interpret opposing guidance cues.
      Among the known intracellular signaling molecules shared by all guidance receptor
      families, Rho GTPases appear to be primary regulators of actin dynamics and
      growth cone guidance. Novel effector molecules complete the picture and suggest
      additional signaling mechanisms.

PMID- 12049931
TI  - The many faces of p75NTR.
AB  - The neurotrophins utilize a complex receptor system consisting of Trk receptor
      tyrosine kinases and the structurally unrelated tumor necrosis factor receptor
      family member, p75(NTR), to confer diverse and sometimes opposing biological
      actions. The recent identification of selective ligands for p75(NTR), novel
      isoforms of this receptor, as well as new signaling partners, suggest that the
      numerous biological actions of the neurotrophins via p75(NTR) may reflect
      selectivity of ligand-receptor interactions and intracellular adaptor protein
      recruitment.

PMID- 12049932
TI  - Retrograde neurotrophin signaling: Trk-ing along the axon.
AB  - Target-derived neurotrophins are required for the growth and survival of
      innervating neurons. When released by postsynaptic targets, neurotrophins bind
      receptors (Trks) on nerve terminals. Activated Trks signal locally within distal
      axons and retrogradely through long axons to distant cell bodies in order to
      promote gene expression and survival. Although the mechanism of retrograde
      neurotrophin signaling is not fully elucidated, considerable evidence supports a
      model in which the vesicular transport of neurotrophin-Trk complexes transmits a
      survival signal that involves PI3K and Erk5. Other, non-vesicular modes of
      retrograde signaling are likely to function in parallel. Recent studies highlight
      the importance of the location of stimulation as a determinant of Trk signaling.
      Defects in signaling from distal axons to cell bodies may be causally related to
      neurodegenerative disorders.

PMID- 12049933
TI  - The GSK3 beta signaling cascade and neurodegenerative disease.
AB  - Biochemical signaling pathways are known to have a critical role in neuronal
      development and function. A growing body of evidence is accumulating to suggest
      that signaling pathways also underlie neurodegeneration and neurodegenerative
      disease. One pathway with a prominent role in neurodegenerative disease is the
      signaling pathway in which the enzyme glycogen synthase kinase 3 (GSK3) is a key
      component. In vitro and in vivo evidence point to a key role for GSK3 in
      promoting neurodegeneration and in Alzheimer's disease plaque and neurofibrillary
      tangle formation. How GSK3 acts in this regard is still open to debate, but it
      may involve both extracellular and nuclear apoptotic activities.

PMID- 12049934
TI  - Receptor trafficking and the plasticity of excitatory synapses.
AB  - Newly discovered features of the trafficking of AMPA receptors to and from the
      postsynaptic membrane of excitatory synapses are now bringing the mechanisms of
      synaptic plasticity into focus. Recent advances, including the existence of
      slots, anchors, transport factors and pathways for activity-dependent control,
      have elucidated the role of the individual AMPA receptor subunits and their
      binding partners. The latest views describe how subunit type dictates the
      assembly of heteromeric receptors, and how these heteromers interact with the
      receptor trafficking machinery and synaptic anchorage factors. Moreover,
      phosphorylation may play an important role in receptor transport and synaptic
      turnover.

PMID- 12049935
TI  - ER transport signals and trafficking of potassium channels and receptors.
AB  - Channels and receptors on the cell surface mediate neuronal signaling. It is
      therefore important to understand how their surface density is controlled. Recent
      studies on the trafficking of potassium channels and neurotransmitter receptors
      have revealed unexpected complexity in the regulation of transport from the
      endoplasmic reticulum to the Golgi apparatus, raising the possibility that the
      surface composition of channels and receptors may be adjusted by controlling
      their export from the endoplasmic reticulum.

PMID- 12049936
TI  - Molecular mechanisms of CaMKII activation in neuronal plasticity.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is thought to be a
      critical mediator of neuronal plasticity that links transiently triggered Ca(2+)
      signals to persistent changes in neuronal physiology. In one of its roles, CaMKII
      is an essential player in the N-methyl-D-aspartate receptor-mediated increase in
      conductance at glutamatergic synapses, a process described as long-term
      potentiation, which serves as a common model for neuronal plasticity and memory.
      Recent studies have used genetic, biochemical, live cell imaging and mathematical
      modeling approaches to investigate neuronal CaMKII and have led to a model of the
      molecular steps of CaMKII translocation and activation that can explain its role
      in neuronal plasticity.

PMID- 12049937
TI  - Selective translation of mRNAs at synapses.
AB  - Synaptic efficacy, a phenomenon that may underlie long-term memory storage, is
      controlled in part by the regulated translation of mRNAs stored in dendrites. The
      molecular basis by which specific mRNAs are selected for translation is beginning
      to emerge and appears to involve at least one mechanism that helps program early
      metazoan development. Because different neural transmitters elicit different
      synaptic responses that rely on local protein synthesis, a number of sequence
      specific mRNA translational regulatory mechanisms are likely to function in
      neurons. Such mechanisms may be inferred from those operating in early
      development and in cognitive disease.

PMID- 12049938
TI  - Spike timing, calcium signals and synaptic plasticity.
AB  - Plasticity at central synapses depends critically on the timing of presynaptic
      and postsynaptic action potentials. Key initial steps in synaptic plasticity
      involve the back-propagation of action potentials into the dendritic tree and
      calcium influx that depends nonlinearly on the action potential and synaptic
      input. These initial steps are now better understood. In addition, recent studies
      of processes as diverse as gene expression and channel inactivation suggest that
      responses to calcium transients depend not only their amplitude, but on their
      time course and on the location of their origin.

PMID- 12049939
TI  - Outside and in: development of neuronal excitability.
AB  - Investigation of the development of excitability has revealed that cells are
      often specialized at early stages to generate Ca(2+) transients. Studies of
      excitability have converged on the central role of Ca(2+) and K(+) channels in
      the plasmalemma that regulate Ca(2+) influx and have identified critical
      functions for receptor-activated channels in the endoplasmic reticulum that allow
      efflux of Ca(2+) from intracellular stores. The parallels between excitability in
      these two locations motivate future work, because comparison of their properties
      identifies shared attributes.

PMID- 12049940
TI  - Retrograde signaling by endocannabinoids.
AB  - Recent studies suggest that endocannabinoids act as retrograde messengers at many
      synapses in the central nervous system. Activation of phospholipases, either
      through calcium-mediated or receptor-mediated signaling, leads to the formation
      and release of endocannabinoids. These lipophilic signaling molecules diffuse to
      nearby presynaptic terminals where they bind to specific G-protein-coupled
      receptors and inhibit neurotransmitter release for tens of seconds. Thus, an
      important physiological role of endocannabinoids may be to provide a mechanism by
      which neurons can rapidly regulate the strength of their synaptic inputs.

PMID- 12049941
TI  - Signaling components that drive circadian rhythms.
AB  - In the past year, knowledge of how information is relayed in the regulation of
      circadian rhythms has advanced considerably. Experiments using genetic knockout
      animals suggest that circadian photoreception consists of an integration of
      multiple signaling pathways. Versatility of clock proteins is seen in terms of
      their function in the central pacemakers versus the periphery. This versatility
      also extends to previously identified molecules, such as retinoid receptors,
      redox factors and mitogen-activated protein kinase, that have newly identified
      roles in circadian signaling pathways. Advances in circadian research over the
      past year include the common themes of redundancy and plasticity.

PMID- 12049942
TI  - Sleep, feeding, and neuropeptides: roles of orexins and orexin receptors.
AB  - Recent studies using molecular genetics in mice and dogs, as well as
      histopathological analyses of human disease, have come to the same conclusion:
      the human sleep disorder narcolepsy is caused by failure of signaling mediated by
      orexin (hypocretin) neuropeptides. These and other findings strongly suggest that
      the orexin system plays a critical role in sleep/wake regulation. In addition,
      the orexin system may link energy homeostasis to the regulation of sleep/wake
      cycles.

PMID- 12049952
TI  - Comparison of breast mammography, sonography and physical examination for
      screening women at high risk of breast cancer in taiwan.
AB  - Recommended surveillance for screening breast cancer, which includes regular
      mammography and clinical breast examination, has long been established in Western
      countries. This strategy may be too costly and unnecessary for countries with low
      incidences of breast cancer. The purpose of the present study is to compare
      breast mammography, sonography and physical examination in screening female
      relatives of breast cancer index cases from the hospital, and their relative
      efficiency. A total of 935 women over 35 years old, who were relatives of breast
      cancer patients, were invited to an annual screening by means of a combination of
      mammography, sonography and physical examination on a single day. A biopsy was
      performed when any of the three investigations indicated a possibility of
      malignancy. A total of 21 breast cancers, including sixteen invasive cancers and
      5 noninvasive cancers, were detected among the 935 high-risk women. Of the
      cancers, 18, including 16 invasive cancers and 3 noninvasive cancers, were
      detected by sonography. In contrast, only 11 invasive cancers were detected by
      mammography, and 7 by physical examination. There were only 14 cancers detected
      by a combination of mammography and physical examination. The 7 (33.3%)
      additional cancers were detected when sonography was added. The sensitivity of
      sonography was 90.4%, which was higher than mammography (52.4%) and physical
      examination (33.3%), or even a combination of these two modalities (66.7%). This
      indicates that sonography is a more accurate screening tool for breast cancer in
      the high-risk group. Although breast sonography has not yet been recommended as a
      routine screening tool for breast cancer in Western countries, it may be superior
      to mammography and physical examination for the screening of Taiwanese high-risk
      female relatives of breast cancer index cases. If it should also be considered as
      a routine adjunct screening modality for Taiwanese women with lower rates of
      breast cancer will need further study.

PMID- 12049951
TI  - Reliability of sacroiliac joint laxity measurement with Doppler imaging of
      vibrations.
AB  - We developed a noninvasive technique, referred to as Doppler imaging of
      vibrations (DIV), to measure laxity of the sacroiliac joint (SIJ). The purpose of
      this study was to examine the reliability of SIJ laxity measurements. A total of
      10 healthy women (mean 29.6 +/- 6 years old) participated in the study. At both
      sides, SIJ laxity was measured with DIV in threshold units (TU). Reliability and
      measurement error were assessed from repeated measurements by five testers on two
      occasions as well as by one experienced tester. Intraclass correlation
      coefficients ranged from 0.53 to 0.80 for all five testers, and from 0.75 to 0.89
      for the one experienced tester. Only changes larger than 1.94 to 3.60 TU (any
      tester) or 1.45 to 2.38 TU (experienced tester) could be confidently detected.
      DIV is a reliable technique for SIJ laxity measurements in healthy subjects, when
      performed by an experienced tester.

PMID- 12049953
TI  - Does dehydration affect thickness of the pyloric muscle? An experimental study.
AB  - Congenital hypertrophic pyloric stenosis (CHPS) is a common condition in infancy
      associated with smooth muscle hypertrophy and resulting in pyloric outlet
      obstruction. The final diagnosis of CHPS is based on precise ultrasonographic
      measurements of length and width of the pyloric muscle. Based on our clinical and
      sonographic experience, we observed that smaller measurements of the pyloric
      muscle were obtained in dehydrated infants than in children examined after proper
      fluid restoration. The clinical importance of these observations was evident
      because false-negative results could be obtained. An experimental animal work
      followed, proving our clinical observation to be true. A significant difference
      of about 30% to 50% was found between measurements of the muscle thickness of the
      gastric and pyloric muscles in a state of water deprivation, as compared with a
      state of full hydration (p < 0.05). Based on our preliminary results, we suggest
      that children with suspected CHPS should be well hydrated before the ultrasound
      (US) examination is performed, to avoid false-negative results and a consequent
      delay in treatment.

PMID- 12049954
TI  - Ovarian stroma flow intensity decreases by age: a three-dimensional power doppler
      ultrasonographic study.
AB  - This was a prospective comparative clinical study to test the hypothesis that the
      flow intensity of the ovarian stroma decreases in the order of the aging process.
      A total of 100 consecutive women who came to our outpatient clinic for Pap smear
      examination were recruited. They were divided into three groups. The premenopause
      group (58 women) had menstruated within the last 3 months and had normal ovaries
      (no polycystic ovary or any pathologic cyst or mass), as demonstrated on the
      baseline ultrasound (US) examination. The perimenopause group (20 women) had last
      menstruated between 3 and 12 months earlier and had normal ovaries. The
      postmenopause group (22 women) had had no menstrual cycle within the last 12
      months and had normal ovaries. Three-dimensional power Doppler US was applied to
      quantify the blood flow and vascularization within the stroma of the bilateral
      ovaries. The results showed that the E2 level decreased in the order of:
      premenopause (mean +/- SD; 40.88 +/- 40.65 pg/mL), perimenopause (22.00 +/- 13.61
      pg/mL), then postmenopause (17.25 +/- 16.40 pg/mL). The vascularization index
      (VI) (6.95 +/- 8.35; 1.11 +/- 0.93; 0.53 +/- 1.75; respectively), flow index (FI)
      (15.98 +/- 7.59; 12.00 +/- 3.86; 5.18 +/- 5.31; respectively) and vascularization
      flow index (VFI) (1.25 +/- 1.59; 0.18 +/- 0.15; 0.09 +/- 0.32; respectively) all
      decreased significantly in the order of premenopause, perimenopause, then
      postmenopause. To the best of our knowledge, this is the first study using 3-D
      power Doppler sonography that proves that the flow intensity decreases along with
      the aging process in the ovarian stroma.

PMID- 12049955
TI  - In vivo quantitation of tumour vascularisation assessed by Doppler sonography in
      rat mammary tumours.
AB  - This study was designed to evaluate high-frequency power Doppler (PDS) and to
      quantify treatment-induced changes in an experimental autochthonous mammary
      tumour model in rats. A total of 13 rats with N-methyl, N-nitroso urea-induced
      mammary tumours were split into three courses; 6 rats were treated with
      epirubicin, 3 received a placebo injection and 4 had irradiation of their tumour
      with a direct electron beam using a single dose of 18 Gy. In all groups,
      treatment began when the tumour area reached at least 1 cm(2) and was preceded by
      the first power Doppler sonography study of the tumour (Echo #1). Echo #2 was
      carried out in the middle of the placebo or epirubicin treatment (after 3 weeks)
      or 7 days after irradiation in the irradiated group. Echo #3 was carried out at
      the end of placebo or epirubicin treatment or 28 days after irradiation. Then
      colour pixel density (CPD) and vascularity index (VI) were quantitated.
      Intraobserver and interobserver variability of the CPD and VI quantitation was
      low (r = 0.99 and 0.97, respectively, for intraobserver and interobserver
      variability of the CPD values). The monitoring of CPD and VI showed an increase
      with time during the observation period. No increase in CPD or VI was observed in
      treated mammary tumours (p < 0.01). Power Doppler sonography quantitation of
      angiogenesis is reproducible, noninvasive and feasible in this in vivo breast
      cancer model. The monitoring of angiogenesis according to different treatments is
      feasible in real-time. Further studies are needed to investigate the predictive
      value of CPD and VI on sensitivity of mammary tumours to anticancer treatment.

PMID- 12049956
TI  - Improved detection and biopsy of solid liver lesions using pulse-inversion
      ultrasound scanning and contrast agent infusion.
AB  - The purpose of this study was to assess the ability of pulse-inversion ultrasound
      (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant
      liver lesions and its impact on patient management (resectability). Additionally,
      to determine the feasibility of US-guided biopsy of new PIUS-findings at the same
      session. A total of 30 patients with known or clinically suspected cancer
      underwent conventional B-mode scanning and PIUS with IV-administered contrast
      agent. The number of liver metastases in the right and the left liver lobe,
      respectively, was recorded. All patients with additional findings by PIUS
      underwent US-guided biopsy. PIUS provided additional information in 18 patients
      (60%); of these, 13 (43%) had additional metastases. Of 19 patients found
      resectable by conventional US, 9 (47%) were considered inoperable using PIUS
      supported by biopsies. Biopsies of additional findings were performed in 17 of 18
      patients. All biopsies of additional findings confirmed malignancy. PIUS with an
      IV contrast agent increased the ability to detect liver metastases compared to
      conventional US scanning. The technique had a high impact on patient management.
      The results showed that PIUS-guided biopsy was possible. PIUS with IV contrast
      will undoubtedly become an important diagnostic tool in the evaluation of
      patients with metastatic liver disease.

PMID- 12049957
TI  - Comparing contrast-enhanced ultrasound to immunohistochemical markers of
      angiogenesis in a human melanoma xenograft model: preliminary results.
AB  - This study compared contrast-enhanced ultrasound (US) measures of tumor
      neovascularity with molecular markers of angiogenesis in a human melanoma
      xenograft model. A total of 14 mice were implanted with a human melanoma cell
      line (WM-9) in the thigh. After 2 to 3 weeks, a tumor, approximately 12 mm in
      diameter, developed. The US contrast agent Optison (Mallinckrodt, St. Louis, MO)
      was injected in a tail vein (dose: 0.4 to 0.6 mL/kg). Power Doppler and pulse
      inversion harmonic imaging (HI) were performed with an Elegra scanner (Siemens
      Medical Systems, Issaquah, WA) and a 7.5 MHz linear array. Frame-rates of 30 Hz
      and 0.5 Hz (intermittent imaging) were used for pulse-inversion HI. After
      surgical removal, specimens were sectioned in the same planes as the US images.
      Immunohistochemical stains for endothelial cells (CD31), vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF) and cyclooxygenase-2
      (COX-2) were performed. Two observers graded the stains (for intensity and
      percent area), and two other observers graded the US imaging modes (for
      fractional tumor neovascularity) on the same scale from 0 to 3. Of the 14 mice, 4
      failed for technical reasons (i.e., n = 10). Linear regressions indicated
      statistically significant correlations between percent area stained with COX-2
      and power Doppler (r = -0.789; p < 0.01), as well as intermittent pulse-inversion
      HI (r = -0.795; p < 0.05). There was a trend toward significance between percent
      area stained with VEGF and intermittent pulse-inversion HI (r = -0.720; 0.05 < p
      < 0.10). No other comparisons were significant. In conclusion, contrast-enhanced
      US measures of tumor neovascularity in a human melanoma xenograft model appear to
      provide a noninvasive marker of angiogenesis corresponding to expression of COX
      2. However, the sample size of this study is small and, until further studies
      have been conducted, these conclusions are preliminary.

PMID- 12049958
TI  - Dopplersonographic measurement of global cerebral circulation time using echo
      contrast-enhanced ultrasound in normal individuals and patients with
      arteriovenous malformations.
AB  - Echo-contrast "bolus tracking" by ultrasound (US) is an exciting new tool to
      study cerebral haemodynamics. In the present study, a global cerebral circulation
      time (CCT) was measured by extracranial Doppler as the time difference of
      contrast bolus arrival between the internal carotid artery and internal jugular
      vein. A total of 64 healthy volunteers and 9 patients with an angiographically
      diagnosed arteriovenous malformation (AVM) were studied. CCT in volunteers and
      patients was calculated as the time interval between the points of 10% rise
      (CCT(1)) and 90% rise (CCT(3)) of the total intensity increase and between the
      turning points (CCT(2)) of the resulting time-intensity curves. In the volunteer
      group, CCT(1) was 5.4 +/- 1.8 s, CCT(2) was 7 +/- 1.3 s and CCT(3) 7.5 +/- 1.8 s.
      CCT results in the AVM group were 2.8 +/- 2.5 s, 3.0 +/- 1.3 s and 4.5 +/- 2.1 s,
      respectively, and differed significantly from the controls. For the first time,
      we could confirm a significant shortening of CCT in patients with cerebral AVM by
      US. The presented test might become a new, additional tool for AVM evaluation and
      follow-up of treatment in these patients.

PMID- 12049959
TI  - Myocardial blood flow measurements in rats with simple pulsing contrast
      echocardiography.
AB  - Relationship between contrast intensity and ultrasound (US) pulsing interval has
      been utilized to quantify myocardial blood flow (MBF) during myocardial contrast
      echocardiography (MCE). We tested if an MCE method employing a simple pulsing
      sequence during intravenous contrast infusion has the ability to quantify MBF in
      rats. We performed MCE in 17 rats using a 5- to 12-MHz broadband transducer
      during microbubble infusion via the femoral vein. Acoustic density (AD) from the
      anterior wall of the left ventricle imaged in the short axis plane was plotted
      against the frame number after shortening the pulsing interval (PI) from 1:20 to
      1:1 end-systolic ECG gating. The relation between AD and frame number was fitted
      to a decay function. The rate of the AD decay was decreased during dipyridamole
      infusion, but was increased by causing coronary stenosis. The AD during long PI
      imaging remained unchanged during the interventions. Estimated MBF by MCE after
      correction by heart rate exhibited a close correlation (r = 0.83) with the
      present "gold standard" of colored microsphere-derived MBF. Thus, the decay rate
      of the contrast intensity obtained with the high-frequency transducer after
      abrupt shortening of PI during intravenous microbubble infusion may provide for
      noninvasive measurement of MBF in rats.

PMID- 12049960
TI  - Elastic modulus measurements of human liver and correlation with pathology.
AB  - Viral hepatitis causes fibrosis in the liver and may change mechanical properties
      of the liver. To evaluate the impact of fibrosis on elastic properties of human
      liver and to investigate potential benefits of ultrasonic elasticity imaging, 19
      fresh human liver samples and 1 hepatic tumor (focal nodular hyperplasia) sample
      obtained during operations were studied. Simple 1-D estimates based on the cyclic
      compression-relaxation method were performed. Elastic modulus values were derived
      from the predetermined strain (controlled by a step motor system) and the stress
      values (measured by an electronic balance). Each specimen subsequently received
      histologic examination and a grade of liver fibrosis was scored from 0 to 5.
      Results show that the elastic modulus values were on the order of several
      hundreds to thousands of Pascals. The elastic modulus generally increased with
      the fibrosis grade, although some discrepancies existed at the middle grades of
      fibrosis (scores 1 to 3). The correlation between the fibrosis score and the
      elastic modulus was significant (p < 0.01) based on the statistical analysis
      using the Pearson correlation method. In addition, the relation between the
      elastic modulus and the fibrosis grade generally exhibited a quadratic trend. It
      was concluded that severity of fibrosis had a good correlation with stiffness of
      the liver. Results also indicated that the elasticity imaging of the liver may
      provide significant clinical values if the elastic modulus can be accurately
      measured.

PMID- 12049961
TI  - Myocardial elastography--a feasibility study in vivo.
AB  - Early detection of cardiovascular diseases has been a very active research area
      in the medical imaging field. Assessment of the local and global mechanical
      functions is one of the major goals of accurate diagnosis. In this study, we
      investigated the feasibility of elastography for estimation and imaging of the
      local cardiac muscle displacement and strain in a human heart in vivo. In its
      noninvasive applications, elastography has been typically used to determine local
      tissue strain through the use of externally applied compression. For our study,
      we utilized the cardiac muscle motion during a cardiac cycle as the mechanical
      stimulus, and acquired successive radiofrequency (RF) data frames of the septal
      and posterior walls over a few cardiac cycles in parasternal and apical views,
      respectively. High-quality cine-loop elastograms were obtained due to high frame
      rates and the resulting low decorrelation noise. Furthermore, the strain contrast
      was higher in the parasternal case, when only the posterior wall was imaged, and
      strain estimation was more robust in the apical view. High repeatability of the
      results was observed through elastographic measurements over several cardiac
      cycles. Finally, an M-mode version of elastography was used to follow part of the
      interventricular septum or the posterior wall over the course of two cardiac
      cycles. Not only do these preliminary results show that elastography is feasible
      in cardiac applications in vivo, but also that it can provide new information
      regarding cardiac motion and mechanical function. Future prospects include
      assessment of the role of elastography in detection of ischemia and infarction.

PMID- 12049962
TI  - Optimal pulse-inversion imaging for microsphere contrast agents.
AB  - Microbubbles are used as contrast agents because they scatter incident ultrasound
      (US) efficiently. Pulse-inversion imaging makes use of the asymmetrical
      difference in response of a bubble to an US pulse and its symmetrical opposite to
      obtain improved contrast. In this theoretical work, the principle of pulse
      inversion imaging is expanded upon by finding the optimal pulse shape to maximize
      the signal from a bubble. Given a limit on driving intensity, a suitable norm of
      the bubble response is maximized using optimal control theory to identify the
      proper pulse/antipulse driving protocol for a single bubble. The optimal pulse
      yields a several-fold increase in the normed response over the best sinusoidal
      pulse of the same driving intensity. It was found that the optimal driving for a
      single bubble also maximizes the nonlinear response of the cloud if its mean
      bubble size is the same as that of the single bubble.

PMID- 12049963
TI  - An in vitro system for Doppler ultrasound flow studies in the stenosed carotid
      artery bifurcation.
AB  - To investigate the correlation between disease severity and Doppler spectral
      measurements in the carotid artery bifurcation, a unique in vitro system has been
      developed that mimics the human vasculature with respect to both anatomy and flow
      perfusion. Agar-based carotid phantoms are perfused with a blood-mimicking fluid
      using a computer-controlled pump and realistic pulsatile flow waveform. A three
      axis translational stage allows the lumen to be interrogated with a 0.6-microL
      Doppler sample volume at the desired spatial intervals using a semiautomated
      acquisition system, to collect 10 cardiac cycles of gated quadrature data at each
      site. Off-line analysis, including a 1024-point FFT, produces a 4-D (i.e., time
      varying 3-D) Doppler velocity data set with 1.3-cm/s velocity resolution and 12
      ms temporal resolution. Using this system, in vitro flow in bifurcations with
      both normal and stenosed lumen geometry (from 30% to 80% stenosis by NASCET
      criteria) can be studied, along with the effect of factors, such as stenosis
      geometry (concentric vs. eccentric) and flow rate, on the observed Doppler
      ultrasound (US) spectra and haemodynamic patterns.

PMID- 12049964
TI  - Ultrasound-based vessel wall tracking: an auto-correlation technique with RF
      center frequency estimation.
AB  - Vessel diameter is related to the distending blood pressure, and is used in
      estimations of vessel stiffness parameters. The vessel walls can be tracked by
      integrating wall velocities estimated by ultrasound (US) Doppler techniques. The
      purpose of this work was to evaluate the performance of the modified
      autocorrelation estimator when applied on vessel wall motion. As opposed to the
      conventional autocorrelation method that only estimates the mean Doppler
      frequency, the modified autocorrelation method estimates both the mean Doppler
      frequency and the radiofrequency (RF) center frequency. To make a systematic
      evaluation of the estimator, we performed computer simulations of vessel wall
      motion, where pulse bandwidth, signal-to-noise ratio (SNR), signal-to
      reverberation ratio, packet size and sample volume were varied. As reference, we
      also analyzed the conventional autocorrelation method and the cross-correlation
      method with parabolic interpolation. Under the simulation conditions considered
      here, the modified autocorrelation method had the lowest bias and variance of the
      estimators. When integrating velocity estimates over several cardiac cycles, the
      resulting tissue displacement curves might drift. This drift is directly related
      to the magnitude of the estimator bias and variance. Hence, the modified
      autocorrelation method should be the preferred choice of method.

PMID- 12049965
TI  - Real-time ultrasound analysis of articular cartilage degradation in vitro.
AB  - The sensitivity of the reflection coefficient, attenuation and velocity to the
      enzymatic degradation of bovine patellar cartilage was evaluated in real-time
      with high-frequency ultrasound (US) (29.4 MHz). These parameters were estimated
      from the radiofrequency (RF) signal, which was recorded at 5-min intervals during
      the digestion of the tissue by collagenase or by trypsin. The coefficient of
      reflection at cartilage surface decreased by 78.5% and 10.5% (p < 0.05) after 6 h
      of exposure to collagenase and 4 h of exposure to trypsin, respectively. During
      the trypsin digestion, the attenuation in cartilage increased by 0.274 dB/mm (p <
      0.05) and the velocity decreased by 7 m/s (p < 0.05). The coefficient of
      reflection at the cartilage surface was the most sensitive acoustic parameter to
      the enzymatic degradation of cartilage and may be the easiest to implement for
      clinical diagnosis of cartilage quality. US velocity was found to be insensitive
      to degradation. The small difference in mean velocity between the control and
      degraded cartilage suggests that a constant predefined US velocity value can be
      used to obtain diagnostically acceptable measurement of the cartilage thickness.

PMID- 12049966
TI  - New approach for modelling ultrasound blood backscatter signal.
AB  - The ultrasound (US) scattered signal from blood has been treated as a random
      signal by many investigators. However, the degree of randomness of a medium is a
      relative term that can change considerably with the resolution of the sensor. In
      this study, the backscattered signal from blood has been looked at as a chaotic
      signal. By this treatment, according to Taken's theorem, a single variable (e.g.,
      amplitude of the blood-backscattered signal) can be used to reconstruct the
      nonlinear dynamics of the blood-scattered signal. Multilayer perceptron neural
      network architecture, with error back-propagation, has been formulated and used
      as a basis for building and testing the chaotic model of the backscattered
      signal. This chaotic model is used successfully as a short-term predictor of the
      backscattered signal from blood-mimicking fluid (BMF) flowing in a vascular flow
      phantom under pulsatile flow. This modelling approach can be useful, for example,
      in detecting blood-borne emboli.

PMID- 12049967
TI  - Tumor vessel destruction resulting from high-intensity focused ultrasound in
      patients with solid malignancies.
AB  - The purpose of this study was to explore the sequential imaging and histologic
      alterations of tumor blood vessels in the patient with solid malignancies after
      extracorporeal treatment of high-intensity focused ultrasound (HIFU). A total of
      164 patients underwent extracorporeal HIFU ablation of malignant solid tumors.
      After HIFU treatment, enhanced magnetic resonance imaging (MRI), color Doppler
      ultrasound (US) imaging, dynamic radionuclide scanning, digital subtraction
      angiography, and histologic study were performed to monitor the response of tumor
      vessels to HIFU ablation. Compared with tumor images in the patients before HIFU,
      clinical images showed an abrupt interruption, followed by the cessation of blood
      flow within the tumor vessels after HIFU treatment. The histologic examination
      indicated that not only the treated tumor cells showed coagulative necrosis, but
      also small tumor vessels were severely damaged by the HIFU treatment. The results
      strongly imply that the damaged tumor vessels might play a critical role in
      secondary tumor cell death, and then indirectly strengthen the destructive force
      of focused US beams on tumor tissue. It is concluded that tumor vessel damage can
      be induced by HIFU, which may be a promising strategy in the treatment of
      patients with solid malignancies.

PMID- 12049968
TI  - Development of validated stability-indicating assay methods--critical review.
AB  - This write-up provides a review on the development of validated stability
      indicating assay methods (SIAMs) for drug substances and products. The
      shortcomings of reported methods with respect to regulatory requirements are
      highlighted. A systematic approach for the development of stability-indicating
      methods is discussed. Critical issues related to development of SIAMs, such as
      separation of all degradation products, establishment of mass balance, stress
      testing of formulations, development of SIAMs for combination products, etc. are
      also addressed. The applicability of pharmacopoeial methods for the analysis of
      stability samples is discussed. The requirements of SIAMs for stability study of
      biotechnological substances and products are also touched upon.

PMID- 12049969
TI  - Stability indicating methods for the determination of loratadine in the presence
      of its degradation product.
AB  - Four stability-indicating procedures have been suggested for determination of the
      non sedating antihistaminic agent loratadine. Loratadine being an ester undergoes
      alkaline hydrolysis and the corresponding acid derivative is produced as a
      degradation product. Its identity was confirmed using IR and MS. The first
      procedure is based on determination of loratadine by HPLC with detection at
      wavelength, 250 nm. Mobile phase is acetonitrile:orthophosphoric acid (35:65)
      using benzophenone as an internal standard. Sensitivity range is 5.00-50.00
      microg/ml. Second determination is a densitometric procedure based on
      determination of loratadine in the presence of its degradate at lambda 246 nm
      using the mobile phase; methanol:ammonia (10:0.15). Sensitivity range is 1.25
      7.50 microg per spot. The third procedure is a spectrophotometric one where a
      mixture of loratadine and its degradate are resolved by first derivative ratio
      spectra. Sensitivity range is found to be 3.00-22.00 microg/ml, upon carrying out
      the measurements at wavelengths 236, 262.4 and 293.2 nm. The fourth procedure is
      based on second derivative spectrophotometry, where D(2) measurements are carried
      out at lambda 266 nm. The sensitivity range is 3.00-22.00 microg/ml. The validity
      of the described procedures was assessed by applying the standard addition
      technique. Statistical analysis of the results have been carried out revealing
      high accuracy and good precision. The suggested procedures could be used for
      determination of loratadine both in pure and dosage forms, as well as in the
      presence of its degradate.

PMID- 12049970
TI  - Stability indicating LC method for the estimation of venlafaxine in
      pharmaceutical formulations.
AB  - A rapid, selective and stability indicating high performance liquid
      chromatographic method was developed and validated for the estimation of
      venlafaxine in pharmaceutical dosage forms. The analysis was done on a Spherisorb
      C8 (4.6 x 250 mm, 5 microm) column. The mobile phase consisted of
      acetonitrile:sodium dihydrogen orthophosphate [0.04 M], pH 6.8 (75:25) at a flow
      rate of 1.5 ml/min. Detection was carried out at a wavelength of 224 nm. The
      developed method was found to give good separation between the pure drug and the
      degraded product. The polynomial regression data for the calibration plots showed
      good linear relationship in the concentration range of 1-10 microg/ml with
      r=0.9999. The method was validated for precision, accuracy, ruggedness and
      recovery. The minimum detectable and minimum quantifiable amounts were found to
      be 150 and 600 ng/ml, respectively. The drug was stable under basic and oxidative
      conditions. However, the sample treated with acid showed an additional peak at a
      retention time of 4.32 min other than the main peak at a retention time of 5.32
      min. Statistical analysis proves that the method is reproducible and selective
      for the estimation of venlafaxine. As the method could effectively separate the
      drug from the degradation product, it can be employed as a stability indicating
      one.

PMID- 12049971
TI  - Determination of the absolute configuration of 2-hydroxyglutaric acid and 5
      oxoproline in urine samples by high-resolution NMR spectroscopy in the presence
      of chiral lanthanide complexes.
AB  - Determination of the absolute configuration of some metabolites in body fluids is
      important for the diagnosis of some inborn errors of metabolism. Presently
      available methods of such determinations are tedious and usually require highly
      specialized instrumentation. In this work, an alternative method, based on high
      resolution nuclear magnetic resonance spectroscopy in the presence of the chiral
      lanthanide shift reagent as an auxiliary additive, has been proposed (NMR/LSR).
      The method involves the lineshape analysis of a chosen multiplet of the one
      dimensional 1H NMR spectrum or application of the two-dimensional 1H-13C
      correlation spectroscopy (HSQC). In order to confirm the resonance assignments
      and to boost the signal-noise ratio, the addition of an amount of racemic analyte
      to the urine sample is recommended. The entire procedure is simple in application
      and demands minimal or no preprocessing of urine samples. The effectiveness of
      the method has been confirmed by finding the expected forms of 2-hydroxyglutaric
      acid and 5-oxoproline in the urine samples of an independently diagnosed patient
      with 2-D-hydroxyglutaric aciduria and 5-L-oxoprolinuria, respectively.

PMID- 12049973
TI  - Accelerated dissolution testing for improved quality assurance.
AB  - In pharmaceutical production of controlled release tablets and capsules, a rapid
      and automated at-line dissolution test for quality assurance of semi-products is
      advantageous. For effective control of the production, the analysis should not
      take more than about an hour, without loss of correlation to the ordinary (USP)
      dissolution test of the final product. For almost a decade, the ACDRA apparatus
      (ACcelerated Dissolution Rate Analysis) have been used for this purpose at
      AstraZeneca Tablet Production Sweden (TPS). In this paper, we give examples on
      different ways to accelerate the dissolution process. We use the USP dissolution
      calibrator tablets of salicylic acid (non-disintegrating type) to illustrate the
      strategy. We investigate the accelerated dissolution of the dissolution
      calibrator tablets, and show how it can be correlated with the dissolution in the
      ordinary USP-II equipment. The dissolution process was accelerated by variation
      of temperature, solvent and stirring. For example, we show that by increasing the
      temperature to 70 degrees C, changing the solvent to water, and increasing the
      stirring, it is possible to accelerate the dissolution by a factor of 5, without
      any loss of correlation to the dissolution process in the ordinary test.

PMID- 12049974
TI  - Simultaneous spectrophotometric determination of mefenamic acid and paracetamol
      in a pharmaceutical preparation using ratio spectra derivative spectrophotometry
      and chemometric methods.
AB  - Four new methods are described for the simultaneous determination of mefenamic
      acid (MEF) and paracetamol (PAR) in their combination. In the first method, ratio
      spectra derivative method, analytical signals were measured at the wavelengths
      corresponding to either maximums or minimums for both drugs in the first
      derivative spectra of the ratio spectra obtained by dividing the standard
      spectrum of one of two drugs in 0.1 M NaOH:methanol (1:9). In the chemometric
      techniques, classical least-squares, inverse least-squares and principal
      component regression (PCR), the training was randomly prepared by using the
      different mixture compositions containing two drugs in 0.1 M NaOH:methanol (1:9).
      The absorbance data was obtained by the measurements at 13 points in the
      wavelength range 235-355 nm in the absorption spectra. Chemometric calibrations
      were constructed by the absorbance data and training set for the prediction of
      the amount of MEF and PAR in samples. In the third chemometric method, PCR, the
      covariance matrix corresponding to the absorbance data was calculated for the
      basis vectors and matrix containing the new coordinates. The obtained calibration
      was used to determine the title drugs in their mixture. Linearity range in all
      the methods was found to be 2-10 microg/ml of MEF and 4-20 microg/ml of PAR. Mean
      recoveries were found satisfactory (>99%). The procedures do not require any
      separation step. These methods were successfully applied to a pharmaceutical
      formulation, tablet, and the results were compared with each other.

PMID- 12049972
TI  - Determination of ethylenediamine tetraacetic acid in injection forms by ion-pair
      chromatography.
AB  - A high performance liquid chromatographic method was developed for the
      determination of ethylenediamine tetraacetic acid (EDTA) in injection forms. The
      method consists of direct extraction of the samples with ethyl acetate; the
      organic layers were evaporated to dryness and further diluted to a 0.025% (w/v)
      copper nitrate in order to achive the formation of the EDTA-copper solution
      complex. The chromatographic separation was performed on a C8 Hypersil column.
      The mobile phase consisted of a mixture of acetonitrile-0.015 M
      tetrabutylammonium hydroxide (10:90, v/v), (pH* 7.0) pumped at a flow rate of 1.5
      ml min(-1). The UV detector was operated at 300 nm. Correlation coefficients of
      the calibration graphs were better than 0.9995, relative standard deviation was
      less than 2.5%. Detection limit of EDTA was found to be 1.97 microg ml(-1).

PMID- 12049975
TI  - Examination of rofecoxib solution decomposition under alkaline and photolytic
      stress conditions.
AB  - Rofecoxib is a highly active and selective cyclo-oxygenase II inhibitor. A
      stability-indicating method for the assay of rofecoxib has been developed using
      reverse-phase high-performance liquid chromatography (HPLC). Stress testing of
      rofecoxib was conducted during the method development and validation. HPLC
      analysis of rofecoxib solutions stressed under alkaline and photolytic conditions
      revealed the presence of several degradates. Two main degradates were determined
      to be the cyclization product formed by photo-cyclization and the dicarboxylate
      formed by ring opening in the presence of base and oxygen. The identities of
      these degradates were confirmed by comparison of UV spectra and HPLC retention
      time with the independently synthesized products. The mechanistic pathways for
      the formation of these degradates are discussed. Further improvement of the HPLC
      method's ruggedness has been made based on these studies.

PMID- 12049976
TI  - Simultaneous development of six LC-MS-MS methods for the determination of
      multiple analytes in human plasma.
AB  - Traditional sequential single analyte method development is both time-consuming
      and labor-intensive. In this report, a concept of simultaneously developing
      multiple liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS)
      methods were proposed. Mass spectrometric and chromatographic conditions as well
      as sample preparation methods for all analytes were optimized concurrently. Mass
      spectrometric conditions for six analytes, i.e. clonidine (CLO), albuterol (ALB),
      fentanyl (FEN), ritonavir (RIT), naltrexone (NAL), and loratadine (LOR), were
      established simultaneously using the Sciex Analyst software. LC-MS-MS
      sensitivities obtained using gradient elution methods on reversed-phase Inertsil
      ODS3 and normal phase Betasil silica columns were compared. Sample extraction
      methods using protein precipitation, liquid/liquid extraction, or solid-phase
      extraction (SPE) were evaluated. Recovery of analytes was determined. Matrix
      effects and interference due to endogenous compounds were investigated. Selection
      of a potential internal standard was discussed.

PMID- 12049977
TI  - 2,6-Dichloroquinone chlorimide and 7,7,8,8-tetracyanoquinodimethane reagents for
      the spectrophotometric determination of salbutamol in pure and dosage forms.
AB  - A simple, rapid and sensitive spectrophotometric method for the determination of
      sulbutamol in pure form and in different pharmaceutical preparations has been
      developed. The charge transfer (CT) reaction between salbutamol as electron donor
      and 2,6-dichloroquinone chlorimide (DCQ) and 7,7,8,8-tetracyanoquinodimethane
      (TCNQ) as a pi-electron acceptor have been spectrophotometrically studied. The
      optimum experimental conditions for these CT reactions have been studied
      carefully. Beer's law is obeyed over the concentration range of 1.0-30.0 microg
      ml(-1) and 2.0-20.0 microg ml(-1) for salbutamol using DCQ and TCNQ,
      respectively. For more accurate results, Ringbom optimum concentration range is
      calculated and found to be 10.0 to 30.0 and 8.0 to 20 microg ml(-1) for
      salbutamol using DCQ and TCNQ, respectively. The Sandell sensitivity is found to
      be 0.011 and 0.010 g cm(-2) for salbutamol using DCQ and TCNQ, respectively,
      which indicate the high sensitivity of the proposed methods. Relative standard
      deviations (R.S.D.) of 0.27 to 0.68% and 0.20 to 1.40% (n=5) were obtained for
      five replicates of salbutamol using DCQ and TCNQ, respectively. The results
      obtained by the two reagents are comparable with those obtained by British
      pharmacopoeia assay for the determination of salbutamol in raw materials and in
      pharmaceutical preparations.

PMID- 12049978
TI  - Quantitative analysis of mannitol polymorphs. FT-Raman spectroscopy.
AB  - Mannitol is a polymorphic excipient which is usually used in pharmaceutical
      products as the beta form, although other polymorphs (alpha and delta) are common
      contaminants. Binary mixtures containing beta and delta mannitol were prepared to
      quantify the concentration of the beta form using FT-Raman spectroscopy. Spectral
      regions characteristic of each form were selected and peak intensity ratios of
      beta peaks to delta peaks were calculated. Using these ratios, a correlation
      curve was established which was then validated by analysing further samples of
      known composition. The results indicate that levels down to 2% beta could be
      quantified using this novel, non-destructive approach. Potential errors
      associated with quantitative studies using FT-Raman spectroscopy were also
      researched. The principal source of variability arose from inhomogeneities on
      mixing of the samples; a significant reduction of these errors was observed by
      reducing and controlling the particle size range. The results show that FT-Raman
      spectroscopy can be used to rapidly and accurately quantitate polymorphic
      mixtures.

PMID- 12049979
TI  - Quantitative analysis of mannitol polymorphs. X-ray powder diffractometry-
      exploring preferred orientation effects.
AB  - Mannitol is a polymorphic parmaceutical excipient, which commonly exists in three
      forms: alpha, beta and delta. Each polymorph has a needle-like morphology, which
      can give preferred orientation effects when analysed by X-ray powder
      diffractometry (XRPD) thus providing difficulties for quantitative XRPD
      assessments. The occurrence of preferred orientation may be demonstrated by
      sample rotation and the consequent effects on X-ray data can be minimised by
      reducing the particle size. Using two particle size ranges (<125 and 125-500
      microm), binary mixtures of beta and delta mannitol were prepared and the delta
      component was quantified. Samples were assayed in either a static or rotating
      sampling accessory. Rotation and reducing the particle size range to <125 microm
      halved the limits of detection and quantitation to 1 and 3.6%, respectively.
      Numerous potential sources of assay errors were investigated; sample packing and
      mixing errors contributed the greatest source of variation. However, the rotation
      of samples for both particle size ranges reduced the majority of assay errors
      examined. This study shows that coupling sample rotation with a particle size
      reduction minimises preferred orientation effects on assay accuracy, allowing
      discrimination of two very similar polymorphs at around the 1% level.

PMID- 12049980
TI  - Optimization and validation of a CZE method for rufloxacin hydrochloride
      determination in coated tablets.
AB  - A simple and rapid capillary electrophoresis method with UV detection was
      developed and validated for the determination of rufloxacin hydrochloride in
      coated tablets. An experimental design strategy (Doehlert design and desirability
      function) allowed the analytical parameters to be simultaneously optimized in
      order to determine rufloxacin hydrochloride with high peak area/migration time
      ratio, good efficiency and short analysis time. Optimized analyses were run using
      boric acid 0.10 M adjusted to pH 8.8 as BGE and setting voltage and temperature
      at 18 kV and 27 degrees C, respectively. Pefloxacin mesylate was used as internal
      standard and run time was about three minutes. The method was validated for the
      drug substance and the drug product according to the ICH3 guidelines. Robustness
      was tested by experimental design using an eight-run Plackett-Burman matrix.

PMID- 12049981
TI  - Simultaneous analysis of flunitrazepam and its major metabolites in human plasma
      by high performance liquid chromatography tandem mass spectrometry.
AB  - A sensitive and specific high performance liquid chromatography-atmospheric
      pressure chemical ionization-tandem mass spectrometry (HPLC-APCI-MS-MS) method
      has been developed for the simultaneous determination of flunitrazepam and its
      major metabolites, 7-aminoflunitrazepam and N-desmethylflunitrazepam, in human
      plasma. After the addition of a deuterium labelled internal standard of
      flunitrazepam, plasma samples were extracted using Oasis(R) MCX solid phase
      extraction cartridges. The compounds were separated on a 5 microm Symmetry C18
      (Waters) column (3.0 x 150 mm, i.d.) with a step gradient of acetonitrile-0.1%
      formic acid at a flow rate of 0.6 ml/min. The overall extraction efficiency was
      more than 89% for all three compounds. The limits of detection were 0.25 g/l for
      flunitrazepam, 0.5 microg/l for 7-aminoflunitrazepam, and 2.0 microg/l for N
      desmethylflunitrazepam. Within-run accuracies for quality-control samples were
      between 92.5 and 101.3% of the target concentration, with coefficients of
      variation <8%. The proposed method enables the unambiguous identification and
      quantitation of flunitrazepam and its major metabolites in both clinical and
      forensic specimens.

PMID- 12049982
TI  - Quantification of the anti-leukemia drug STI571 (Gleevec) and its metabolite (CGP
      74588) in monkey plasma using a semi-automated solid phase extraction procedure
      and liquid chromatography-tandem mass spectrometry.
AB  - Signal Transduction Inhibitor 571 (STI571, formerly known as CGP 57148B) or
      Gleevec received fast track approval by the US Food and Drug Administration (FDA)
      for treatment of chronic myeloid leukemia (CML). STI571 (Gleevec) is a
      revolutionary and promising new oral therapy for CML, which functions at the
      molecular level with high specificity. The dramatic improvement in efficacy
      compared with existing treatments prompted an equally profound increase in the
      pace of development of Gleevec. The duration from first dose in man to completion
      of the New Drug Application (NDA) filing was less than 3 years. In addition,
      recently, FDA approved Gleevec for the treatment of gastrointestinal stromal
      tumor (GIST). In order to support all toxicokinetic (TK) studies with sufficient
      speed to meet various target dates, a semi-automated procedure using solid phase
      extraction (SPE) was developed and validated. A Packard Multi-Probe I and a SPE
      step in a 96-well plate format were utilized. A 3M Empore octyl (C(8))-standard
      density 96-well plate was used for plasma sample extraction. A Sciex API 3000
      triple quadrupole mass spectrometer with an atmospheric pressure chemical
      ionization (APCI) interface operated in positive ion mode was used for detection.
      Lower limits of quantification of 1.00 and 2.00 ng/ml were attained for STI571
      and its metabolite, CGP 74588, respectively. The method proved to be rugged and
      allowed the simultaneous quantification of STI571 and CGP 74588 in monkey plasma.
      Herein, assay development, validation, and representative concentration-time
      profiles obtained from TK studies are presented.

PMID- 12049983
TI  - LC determination of enrofloxacin.
AB  - A simple, rapid and sensitive high-performance liquid chromatographic (HPLC)
      method was developed for the assay of enrofloxacin in raw material and injection.
      The validation method yielded good results and included the range, linearity,
      precision, accuracy, specificity, recovery, limit of detection (LOD) and limit
      quantification (LOQ) values. The HPLC separation was carried out by reversed
      phase chromatography on a C-18 absorbosphere column (150 x 4.6 mm i.d. 5 microm
      particle size) with a phase composed of sodium acetate (pH 4.7; 0.1 M):
      acetonitrile (60:40, v/v; pH 5.0), pumped isocratically at a flow rate of 1.5 ml
      min(-1). The effluent was monitored at 278 nm with the eluting solvent. The
      calibration graph for enrofloxacin was linear from 10.0 to 80.0 microg ml(-1).

PMID- 12049984
TI  - LC determination of piroxicam in human plasma.

PMID- 12049985
TI  - Selective spectrophotometric determination of phenolic beta-lactam antibiotics.
AB  - Two simple and selective spectrophotometric methods were developed for the
      quantitative determination of cefoperazone sodium, cefadroxil monohydrate,
      cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their
      pharmaceutical formulations. The methods are based on the selective oxidation of
      these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense
      yellow coloured product (lambda(max)=397 nm). The reaction conditions were
      studied and optimized. Beer's plots were obeyed in a general concentration range
      of 5-30 microg ml(-1) with correlation coefficients not less than 0.9979 for the
      four drugs with the two reagents. The methods are successfully applied to the
      analysis of pharmaceutical formulations containing amoxicillin, either alone or
      in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They
      were also applied to the analysis of the other three studied drugs in vials,
      capsules, tablets and suspensions with good recovery; percent ranged from 99.7
      (+/-0.46) to 100.32 (+/-1.05) in the Ce (IV) method and 99.6 (+/-0.50) to 100.3
      (+/-1.32) in the Fe (III) method. Interferences from other antibiotics and
      additives products were investigated.

PMID- 12049986
TI  - Spectrophotometric determination of alendronate in pharmaceutical formulations
      via complex formation with Fe(III) ions.
AB  - The formation of the complex between alendronate, non-chromophoric bisphosphonate
      drug important for the treatment of a variety of bone diseases, and iron(III)
      chloride in perchloric acid solution was studied. The stoichiometric ratio of
      alendronate to Fe(III) ions in the chromophoric complex was determined to be 1:1.
      The conditional stability constant was logK'(ave)=4.50(SD=0.15), indicating that
      the Fe(III)-alendronate complex is a complex of medium stability. The optimum
      conditions for this reaction were ascertained and a spectrophotometric method was
      developed for the determination of alendronate in the concentration range 8.1
      162.5 microg ml(-1), the detection limit being 2 microg ml(-1). The method was
      validated for the direct determination of alendronate in tablet dosage
      formulations.

PMID- 12049987
TI  - Automatic potentiometric flow titration procedure for ascorbic acid determination
      in pharmaceutical formulations.
AB  - A flow procedure for the determination of ascorbic acid in pharmaceutical
      formulations exploiting potentiometric titration is described. The method is
      based on the reduction of IO3- by ascorbic acid and the detection was carried out
      employing a flow-through ion selective electrode for iodide. The flow network
      controlled by a microcomputer was designed to implement multicommutation for ease
      of operation and robustness. The titration system allowed the determination of
      ascorbic acid in pharmaceutical formulations with concentrations ranging from 7.5
      to 15.0 mmol l(-1). No significant differences at the 95% confidence level were
      observed in comparison with results obtained by a manual procedure. Merit figures
      of results such as a relative standard deviation of 1.0% (n=6) and a reagent
      consumption of 21.4 mg IO3- per determination were obtained.

PMID- 12049988
TI  - Atherosclerotic cardiovascular disease: new approaches to risk assessment and
      intervention. Introduction.

PMID- 12049989
TI  - Identification and treatment of individuals at high risk of coronary heart
      disease.
AB  - Low-density lipoprotein (LDL) cholesterol reduction remains the cornerstone of
      coronary heart disease (CHD) prevention. The most dramatic and consistent
      reductions in LDL cholesterol and CHD risk are achieved with statin therapy.
      Identification of individuals at high CHD risk is important, not only for
      initiating appropriate treatment and minimizing morbidity and mortality but also
      for optimizing the cost-effectiveness of such treatment. A simple method for
      identifying high-risk individuals is to identify those with preexisting
      atherosclerotic disease, diabetes, or familial hypercholesterolemia (FH).
      Treatment options for achieving LDL cholesterol goals in high-risk patients
      include statins, bile acid sequestrants, niacin, and plant stanols. Statin
      therapy should be instituted at a dose likely to result in achievement of LDL
      cholesterol goals based on average response; it should then be aggressively
      titrated if the goals are not achieved. If LDL cholesterol goals are not achieved
      with maximal statin therapy, combination with a bile acid sequestrant, niacin,
      and/or stanols should be considered. Options likely to be available in the near
      future include more efficacious statins with greater potential for reducing LDL
      cholesterol in all patients but especially in high-risk patients, such as those
      with FH, enabling a greater proportion to achieve LDL cholesterol goals. Other
      options that may soon be available as additive agents to statins to achieve
      greater LDL cholesterol reductions include bile acid transport inhibitors and
      cholesterol absorption inhibitors.

PMID- 12049990
TI  - Management of dyslipidemia.
AB  - The 2 principal approaches to management of dyslipidemias are lifestyle
      intervention and lipid-modifying drug therapy. Recent revisions to the American
      Heart Association's dietary guidelines for reducing cardiovascular disease
      emphasize an overall healthy eating pattern and maintenance of appropriate body
      weight, together with achieving a desirable blood pressure and a desirable
      lipoprotein profile. New National Cholesterol Education Program treatment
      guidelines include a scoring system for calculating coronary heart disease (CHD)
      risk that is adapted from the Framingham Heart Study, as well as a category of
      CHD risk equivalents (e.g., diabetes) that will encourage more aggressive
      therapeutic intervention for individuals at high short-term risk for CHD, even in
      the absence of clinically evident coronary disease. Classes of lipid-modifying
      drugs include bile acid sequestrants (resins), fibrates, and statins, with each
      class exerting different effects on the lipid profile. Nicotinic acid (niacin) is
      also an approved lipid-modifying agent. The armamentarium for treating lipid
      disorders and atherosclerosis now includes statins that can decrease low-density
      lipoprotein (LDL) cholesterol levels by up to 55%, as well as a resin with
      improved tolerability. In patients with high levels of LDL cholesterol and
      triglycerides, together with low concentrations of high-density lipoprotein
      cholesterol, combination therapy may be effective. Moreover, researchers are
      currently investigating the development of drugs directed at molecular targets,
      including cholesterol esterification and accumulation in macrophage foam cells
      (e.g., inhibiting acyl-coenzyme A : cholesterol acyltransferase), degradation of
      atherosclerotic plaque (e.g., decreasing the expression of matrix
      metalloproteinases), and reverse cholesterol transport (e.g., stimulating ATP
      binding cassette transporter A1).

PMID- 12049991
TI  - Lipid management in diabetic patients: lessons from prevention trials.
AB  - Diabetes is associated with greatly enhanced risk for coronary heart disease
      (CHD), a correlation that justifies aggressive risk intervention in diabetic
      individuals. Lipid abnormalities in diabetes frequently consist of elevated
      triglyceride and low-density lipoprotein cholesterol levels and low high-density
      lipoprotein cholesterol levels. Subgroup analyses of primary and secondary
      prevention trials with fibrates and statins indicate that lipid modification in
      diabetic patients is associated with significant CHD risk reduction. In 1
      angiographic study (Diabetes Atherosclerosis Intervention Study) fibrate
      treatment was shown to reduce the rate of atherosclerotic progression. A primary
      prevention study of statin treatment (West of Scotland Coronary Prevention Study)
      showed reduced risk for progression to diabetes in a post hoc analysis. Optimal
      lipid-modifying treatment in individuals with diabetes remains to be defined.
      Upcoming trials with diabetic cohorts will improve our understanding of how lipid
      treatment affects CHD risk in this patient population.

PMID- 12049992
TI  - Who is at risk for atherosclerotic disease? Lessons from intravascular
      ultrasound.
AB  - The hypothesis that arterial wall remodeling permits accumulation of a large
      atherosclerotic burden before there is any detectable narrowing of the vessel
      lumen has received support from necropsy and intravascular ultrasound (IVUS)
      studies. In a series of transplant donors assessed by IVUS, coronary atheromas
      were found in 17% of those younger than 20 years, 37% of those aged 20 to 29
      years, and 60% of those aged 30 to 39 years, whereas angiography results were
      negative in 97% of this population. Necropsy data indicate a similar age-related
      prevalence and suggest that atherosclerosis risk factors are operative from a
      very early age. The IVUS findings show that disease is characteristically diffuse
      and involves the entire arterial tree, with progression including formation of
      multiple, potentially rupture-prone plaques that are not associated with vessel
      stenosis. These findings indicate the need for aggressive and early systemic
      intervention that targets modifiable risk factors to reduce coronary artery
      disease morbidity and mortality in the general population.

PMID- 12049994
TI  - Regulatory enzymes of lipid metabolism in LA/N-cp rats.
AB  - Hepatic activities of rate limiting enzymes in fatty acid and cholesterol
      synthesis and cholesterol degradation were determined in lean and obese LA/N-cp
      rats. The hepatic activities of acetyl-CoA carboxylase and fatty acid synthetase,
      the key enzymes of fatty acid synthesis and 3-hydroxy-3-methylglutaryl coenzyme A
      reductase (the rate limiting enzyme in cholesterol synthesis), were increased 2
      fold in the obese rats as compared with their lean littermates. In contrast, the
      activity of cholesterol 7alpha-hydroxylase, the rate limiting enzyme of
      cholesterol degradation to bile acids, was significantly decreased by 28% in the
      obese group as compared with the control group. Significantly, compared with the
      control group, the obese animals exhibited similar magnitudes of differences in
      the activities of the above enzymes even when they were pair-fed with the control
      animals. Thus these differences in the obese group are not due to hyperphagia but
      possibly to hypersecretion of the lipogenic hormone, insulin in this strain.
      These results indicate that the LA/N-cp obese rat has twice the capacity to
      synthesize body fat and cholesterol but has a reduced capacity to degrade the
      cholesterol, leading to increased accumulation of cholesterol and fat.

PMID- 12049993
TI  - A look to the future: new treatment guidelines and a perspective on statins.
AB  - New National Cholesterol Education Program treatment guidelines incorporate a
      global measure of coronary heart disease (CHD) that alters risk categorization in
      primary prevention by identifying individuals with CHD risk equivalence on the
      basis of estimated absolute CHD risk. Increasing recognition of the association
      of on-treatment non-high-density lipoprotein (HDL) cholesterol levels with risk
      of CHD events is also reflected in the new guidelines by incorporation of
      secondary non-HDL cholesterol goals. The increased complexity of the guidelines
      and the likelihood of more individuals being assigned to higher risk groups with
      lower low-density lipoprotein (LDL) cholesterol goals is of some concern, because
      most patients receiving lipid-lowering therapy do not achieve current guideline
      LDL cholesterol goals. Increased potency of LDL cholesterol-lowering drugs would
      be of value in enabling more patients to achieve goals.

PMID- 12049995
TI  - Hyperlipidemic effects of trans fatty acids are accentuated by dietary
      cholesterol in gerbils.
AB  - Trans isomers of dietary fatty acids, generated during the commercial
      hydrogenation of unsaturated fats, may contribute to coronary heart disease (CHD)
      in humans by interfering with lipid metabolism. To examine this possibility in a
      fat-sensitive model, the Mongolian gerbil (Meriones unguiculatus) was used to
      compare the cholesterolemic and triglyceridemic potential of modest increments of
      trans fatty acids from partially hydrogenated soybean oil with other saturated
      fatty acids in the presence and absence of dietary cholesterol. Age-, dose-, and
      time-dependent effects were examined in weanling, 6-month-old, and 1-year-old
      gerbils. Although lipoprotein metabolism in weanling gerbils was initially
      refractory to trans fat, even as perturbations by saturated fatty acids were
      demonstrable, these gerbils eventually (after 16 weeks) developed a trans-induced
      hypercholesterolemia that was intermediate between the response to 16:0 and 12:0
      + 14:0. The hepatic and plasma 18:1/18:2 cholesteryl ester (CE) ratio was
      depressed by trans in a manner similar to saturated fatty acids. The 6-month-old
      gerbils readily developed hypertriglyceridemia but not hypercholesterolemia,
      again revealing a decrease in the plasma 18:1/18:2 CE ratio. The 1-year-old
      gerbils revealed a dose-related (0, 5, 10%en as trans) elevation in total
      cholesterol (TC), and especially triglycerides (TG), that was accentuated by
      0.04% dietary cholesterol. Increases in plasma lipids were again accompanied by a
      significant decrease in the mass of hepatic esterified cholesterol, particularly
      18:1-cholesteryl esters. Thus, dietary trans-fatty acids induce age-, time-, and
      dose-dependent modulations in gerbil plasma lipids associated with decreased 18:1
      cholesteryl esters. Further investigation with gerbils may reveal mechanisms by
      which trans fat consumption disturbs lipoprotein metabolism.

PMID- 12049996
TI  - Antimicrobial activity of lipids added to human milk, infant formula, and bovine
      milk.
AB  - Lipids previously shown to have antiviral and antibacterial activity in buffers
      were added to human milk, bovine milk, and infant formulas to determine whether
      increased protection from infection could be provided to infants as part of their
      diet. Fatty acids and monoglycerides with chain lengths varying from 8 to 12
      carbons were found to be more strongly antiviral and antibacterial when added to
      milk and formula than long chain monoglycerides. Lipids added to milk and formula
      inactivated a number of pathogens including respiratory syncytial virus (RSV),
      herpes simplex virus type 1 (HSV-1), Haemophilus influenzae, and Group B
      streptococcus. The results presented in this study suggest that increased
      protection from infection may be provided to infants at mucosal surfaces, prior
      to the digestion of milk and formula triglycerides, by the addition of
      antimicrobial medium chain monoglycerides to an infant's diet.

PMID- 12049997
TI  - Tissue specificity of selenoprotein gene expression in rats.
AB  - To investigate the tissue-specific effects of inadequate, adequate, and high
      selenium intake on selenoprotein gene expression and enzyme activity, weanling
      rats were fed a selenium-deficient diet or the same diet supplemented with 0.1 or
      2.0 mg of selenium/kg of diet for 91 days. No significant differences in growth
      were observed. In liver, transcription of genes for cellular glutathione
      peroxidase, type I iodothyronine 5'-deiodinase, and selenoprotein P was
      unaffected by selenium intake. Steady-state levels of mRNA for glutathione
      peroxidase and selenoprotein P were higher in liver than in kidney. For
      iodothyronine 5' deiodinase in the opposite was true. In liver, selenium
      deficiency reduced glutathione peroxidase mRNA by 89% and virtually abolished
      enzyme activity. For iodothyronine 5' deiodinase, mRNA and enzyme activity were
      reduced 69 and 70%, respectively. In kidney, selenium deprivation decreased
      glutathione peroxidase mRNA by 91% and reduced enzyme activity to nearly zero.
      For iodothyronine 5'-deiodinase, decreases in mRNA and enzyme activity were 19
      and 62%, respectively. Reductions in selenoprotein P mRNA were 50% in kidney but
      only 14% in liver. The only difference in the effects between the two supplements
      was in liver, where iodothyronine 5'-deiodinase activity was reduced by
      increasing the selenium supplement above a nutritionally adequate level. Hence,
      for these selenoproteins, mRNA turnover appears to be the pretranslational
      process most sensitive to selenium intake. In addition, selenoprotein mRNAs are
      stabilized differentially in selenium deficiency, depending upon the tissue
      examined. Percentage changes in the activity of selenoenzymes were not always the
      same as the changes in their mRNA levels. This suggests that other processes,
      including translation and protein turnover, may determine the ultimate level of
      enzyme activity attained in response to dietary selenium intake.

PMID- 12049998
TI  - Fructose metabolizing enzymes in the rat liver and metabolic parameters:
      Interactions between dietary copper, type of carbohydrates, and gender.
AB  - This study was conducted to determine the effects of nutrient interactions
      between dietary carbohydrates and copper levels on fructose-metabolizing hepatic
      enzymes in male and female rats. Male and female rats were fed diets for 5 weeks
      that were either adequate or deficient in copper that contained either starch or
      fructose. Rats of both sexes fed fructose as compared with those fed starch
      showed higher activity of hepatic fructose metabolizing enzymes. There were also
      significant differences in fructose metabolism of liver between the male and
      female rats. Female rats had lower hepatic ketohexokinase and triose kinase but
      higher triosephosphate isomerase activities compared with male rats. Male rats
      fed copper-deficient diets had lower aldolase B activity compared with those fed
      copper-adequate diets. Female rats fed copper-deficient diets had higher
      triosephosphate isomerase activity compared with rats fed copper-adequate diets.
      Our data suggest that gender differences in hepatic fructose metabolism may not
      be the primary reason for the severity of copper deficiency syndrome in male rats
      fed copper-deficient diet with fructose.

PMID- 12050000
TI  - Cardiac levels of fibronectin, laminin, isomyosins, and cytochrome c oxidase of
      weanling rats are more vulnerable to copper deficiency than those of postweanling
      rats.
AB  - The relative quantities of cardiac laminin, fibronectin, cytochrome c oxidase
      (CCO), and isomyosin types were studied by gel electrophoresis in male rats fed
      copper-deficient diets beginning either from the time of weaning for 5 weeks or
      from 5 weeks postweaning for 6 weeks with one group of copper-repleted rats.
      Increased levels of fibronectin and V(3) isomyosin but decreased levels of CCO
      subunit IV and laminin were found in weanling copper-depleted rats. In contrast,
      postweanling copper-depleted rats exhibited only increased levels of fibronectin
      and decreased levels of cardiac CCO subunit IV. Repletion of copper-deficient
      rats for 6 weeks was not sufficient to restore CCO subunit IV to the same level
      as controls. These results confirm that biochemical lesions in the basal laminae
      are a result of copper restriction. The decreased nuclear encoded subunits of CCO
      may help explain some of the mitochondrial pathology observed in dietary copper
      restriction. Increased V(3) isomyosin levels with low ATPase activity may help to
      conserve to a limited extent the ATP levels in copper-deficient cardiac tissue.
      These protein changes are consistent with the known morphological alterations of
      hearts from copper-restricted rats.

PMID- 12049999
TI  - Expression of apolipoprotein A-I mRNA in liver and intestine of cecectomized rats
      fed beet fiber.
AB  - Sham-operated and cecectomized rats were fed a cholesterol-free diet with no
      added fiber (fiber-free) for 10 days, followed by the diet of 15% beet fiber for
      10 days. The plasma cholesterol concentrations in rats fed the fiber-free diet
      were not significantly different between sham-operated and cecectomized groups.
      Plasma cholesterol concentrations in sham-operated rats were decreased by feeding
      the beet fiber diet, whereas those in cecectomized rats did not change. Final
      plasma total cholesterol concentrations in cecectomized rats were significantly
      higher than in sham-operated rats. This difference was due mainly to lower HDL
      cholesterol concentrations. The cecectomized rats also tended to have higher
      apolipoprotein A-I concentrations in plasma. Northern blot analysis revealed that
      the relative concentrations of ileal apolipoprotein A-I mRNA were the same in the
      two groups, while hepatic apolipoprotein A-I mRNA levels were significantly
      higher in cecectomized rats than in sham-operated rats. These data demonstrate
      that the cecectomy abolished the hepatic apolipoprotein A-I mRNA-lowering effect
      of dietary beet fiber, and it is suggested that the cecum plays an important role
      in the regulation of hepatic apolipoprotein A-I expression which seems to be
      responsible for the hypocholesterolemic effect of dietary beet fiber.

PMID- 12050001
TI  - A method for the determination of betaine in tissues using high performance
      liquid chromatography.
AB  - Betaine is a major metabolite of choline in liver and kidney and may be an
      important product of choline metabolism in other tissues. The available methods
      for assay of betaine, however, are time consuming and relatively insensitive. We
      describe a modification of published methods that provides a sensitive and
      specific assay for betaine by derivatization and HPLC separation with UV
      quantitation. Betaine and other water-soluble choline metabolites are extracted
      from biological samples and separated by HPLC based on mobility of 14C-labeled
      internal standards. The betaine fraction is collected and derivatized with 4'
      bromo-phenacyl triflate. The betaine-triflate derivative is quantitated by UV
      absorbance and the result is corrected for possible losses due to incomplete
      extraction recovery and incomplete derivatization by simultaneous measurement of
      radioactivity from the derivatized 14C-betaine internal standard. Betaine
      concentrations determined with this procedure are reported for several adult and
      fetal rat tissues.

PMID- 12050002
TI  - Thermodynamics and bioenergetics.
AB  - Bioenergetics is concerned with the energy conservation and conversion processes
      in a living cell, particularly in the inner membrane of the mitochondrion. This
      review summarizes the role of thermodynamics in understanding the coupling
      between the chemical reactions and the transport of substances in bioenergetics.
      Thermodynamics has the advantages of identifying possible pathways, providing a
      measure of the efficiency of energy conversion, and of the coupling between
      various processes without requiring a detailed knowledge of the underlying
      mechanisms. In the last five decades, various new approaches in thermodynamics,
      non-equilibrium thermodynamics and network thermodynamics have been developed to
      understand the transport and rate processes in physical and biological systems.
      For systems not far from equilibrium the theory of linear non-equilibrium
      thermodynamics is used, while extended non-equilibrium thermodynamics is used for
      systems far away from equilibrium. All these approaches are based on the
      irreversible character of flows and forces of an open system. Here, linear non
      equilibrium thermodynamics is mostly discussed as it is the most advanced. We
      also review attempts to incorporate the mechanisms of a process into some
      formulations of non-equilibrium thermodynamics. The formulation of linear non
      equilibrium thermodynamics for facilitated transport and active transport, which
      represent the key processes of coupled phenomena of transport and chemical
      reactions, is also presented. The purpose of this review is to present an
      overview of the application of non-equilibrium thermodynamics to bioenergetics,
      and introduce the basic methods and equations that are used. However, the reader
      will have to consult the literature reference to see the details of the specific
      applications.

PMID- 12050003
TI  - Kinetics of solid state stability of glycine derivatives as a model for peptides
      using differential scanning calorimetry.
AB  - Kinetics of solid state stability of seven derivatives of 3,5-disubstituted
      tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT) of glycine as a model for amino
      acids and peptide drugs were studied using differential scanning calorimetry
      (DSC). Each DSC curve for each derivative showed an endothermic peak followed by
      an exothermic one, which could be attributed to the melting and decomposition,
      respectively. The decomposition activation energy of each derivative was
      calculated using the Augis and Bennet, Kissinger equations and Mahadevan
      approximation. Also, the melting activation energies as well as the thermodynamic
      parameter (enthalpy) for the investigated derivatives were evaluated. The
      relative stability of the derivatives in the solid state according to the
      calculated values of the decomposition activation energy, frequency factors and
      half-life for each derivative could be determined.

PMID- 12050004
TI  - Local dynamic properties of the heme pocket in native and solvent-induced molten
      globule-like states of cytochrome c.
AB  - We report the Soret absorption band, down to cryogenic temperature, of native and
      molten-globule-like state of horse heart cytochrome c. The band profile is
      analyzed in terms of vibronic coupling of the heme normal modes to the electronic
      transition in the framework of the Franck-Condon approximation. From the
      temperature dependence of the Gaussian broadening and of the peak position, we
      obtain information on the 'bath' of low frequency harmonic motions of the heme
      group within the heme pocket. The reported data indicate that, compared to the
      native state, the less rigid tertiary structure of the molten globule is
      reflected in a higher flexibility of the heme pocket and in greater
      conformational disorder, allowing the transduction of large-amplitude motion of
      the protein to the dynamics of the heme pocket.

PMID- 12050005
TI  - Structural electrochemical study of hemoglobin by in situ circular dichroism thin
      layer spectroelectrochemistry.
AB  - Secondary and tertiary or quaternary structural changes in hemoglobin (HB) during
      an electroreduction process were studied by in situ circular dichroism (CD)
      spectroelectrochemistry with a long optical path thin-layer cell. By means of
      singular value decomposition least-squares analysis, CD spectra in the far-UV
      region give two similar alpha components with different CD intensity, indicating
      slight denaturation in the secondary structures due to the electric field effect.
      CD spectra in the Soret band show a R-->T transition of two quaternary structural
      components induced by electroreduction of the heme, which changes the redox
      states of the center ion from Fe3+ to Fe2+ and the co-ordination number from 6 to
      5. The double logarithmic analysis shows that electroreduction of hemoglobin
      follows a chemical reaction with R-->T transition. Some parameters in the
      electrochemical process were obtained: formal potential, E0'=-0.167 V;
      electrochemical kinetic overpotential, deltaE0=-0.32 V; standard electrochemical
      reaction rate constant, k0=1.79 x 10(-5) cm s(-1); product of electron transfer
      coefficient and electron number, alphan=0.14; and the equilibrium constant of R-
      >T transition, Kc=9.0.

PMID- 12050006
TI  - Fluorescence properties of tryptophan residues in the monomeric d-chain of
      Glossoscolex paulistus hemoglobin: an interpretation based on a comparative
      molecular model.
AB  - The primary structure of the 142 residue Glossoscolex paulistus d-chain
      hemoglobin has been determined from Edman degradation data of 11 endo-Glu-C
      peptides and 11 endo-Lys-C peptides, plus the results of Edman degradation of the
      intact globin. Tryptophan occupies positions 15, 33 and 129. Homology modeling
      allowed us to assign the positions of these Trp residues relative to the heme and
      its environment. The reference coordinates of the indole rings (average
      coordinates of the C(varepsilon2) and C(delta2) atoms) for W15 and W129 were 16.8
      and 18.5 A, respectively, from the geometric center of the heme, and W33 was
      located in close proximity to the heme group at a distance which was
      approximately half of that for W15 and W129. It was possible to identify three
      rotamers of W33 on the basis of electrostatic and Van der Waals energy criteria.
      The calculated distances from the center of the heme were 8.3, 8.4 and 9.1 A for
      Rot1, Rot2 and Rot3, respectively. Radiationless energy transfer from the excited
      indole to the heme was calculated on the basis of Forster theory. For W33, the
      distance was more important than the orientation factor, kappa(2), due to its
      proximity to the heme. However, based on kappa(2), Rot2 (kappa(2)=0.945) was more
      favorable for the energy transfer than Rot1 (kappa(2)=0.433) or Rot3
      (kappa(2)=0.125). In contrast, despite its greater distance from the heme, the
      kappa(2) of W129 (2.903) established it as a candidate to be more efficiently
      quenched by the heme than W15 (kappa(2)=0.191). Although the Forster approach is
      powerful for the evaluation of the relative efficiency of quenching, it can only
      explain pico- and sub-nanosecond lifetimes. With the average lifetime, <tau>=3
      ns, measured for the apomonomer as the reference, the lifetimes calculated for
      each emitter were: W33-1 (1 ps), W33-2 (2 ps), W33-3 (18 ps), W129 (100 ps), and
      W15 (600 ps). Experimentally, there are four components for oxymonomers at pH 7:
      two long ones of 4.6 and 2.1 ns, which contribute approximately 90% of the total
      fluorescence, one of 300 ps (4%), and the last one of 33 ps (7.4%). It is clear
      that the equilibrium structure resulting from homology modeling explains the sub
      nanosecond fluorescence lifetimes, while the nanosecond range lifetimes require
      more information about the protein in solution, since there is a significant
      contribution of lifetimes that resemble the apo molecule.

PMID- 12050007
TI  - Polybrene increases retrovirus gene transfer efficiency by enhancing receptor
      independent virus adsorption on target cell membranes.
AB  - Cationic polymers, such as polybrene and protamine sulfate, are typically used to
      increase the efficiency of retrovirus-mediated gene transfer, however, the
      mechanism of their enhancement of transduction has remained unclear. As
      retrovirus transduction is fundamentally limited by the slow diffusion of virus
      to the target cell surface, we investigated the ability of polybrene to modulate
      this initial transport step. We compared the ability of both envelope (gp70) and
      capsid (p30) protein based assays to quantitate virus adsorption and found that
      p30 based assays were more reliable due to their ability to distinguish virus
      binding from free gp70 binding. Using the p30 based assay, we established that
      polybrene concentrations, which yielded 10-fold increases in transduction also,
      yielded a significant increase in virus adsorption rates on murine fibroblasts.
      Surprisingly, this enhancement, and adsorption in general, were receptor and
      envelope independent, as adsorption occurred equivalently on receptor positive
      and negative Chinese hamster ovary cells, as well as with envelope positive and
      negative virus particles. These findings suggest that the currently accepted
      physical model for early steps in retrovirus transduction may need to be
      reformulated to accommodate an initial adsorption step whose driving force does
      not include the retrovirus concentration, and the reclassification of currently
      designated 'receptor' molecules as fusion triggers. The implication of these
      findings with respect to the development of targeted retrovirus-mediated gene
      therapy protocols is discussed.

PMID- 12050008
TI  - Nucleosome organization on Kluyveromyces lactis centromeric DNAs.
AB  - The preferential assembly of specialized nucleosomes on budding yeast centromeres
      can be due either to the higher stability of specialized centromeric nucleosomes
      and/or to the lower stability of canonical centromeric nucleosomes with respect
      to bulk nucleosomes. We have evaluated the thermodynamic stability of canonical
      nucleosomes, assembled on Kluyveromyces lactis centromeric DNAs, with a
      competitive reconstitution assay and a theoretical method recently developed by
      us. The results, obtained by both methods, show that all five known centromeric
      DNAs from K. lactis are able to organize canonical nucleosomes, characterized by
      higher stability with respect those of bulk DNA. With 'footprinting' and
      theoretical prediction, based on sequence-dependent DNA elasticity, we have found
      that centromeric canonical nucleosomes are characterized by nucleosome dyad axis
      multiple positioning, rotationally phased. The isoenergetic nucleosome multiple
      positions are relevant in understanding the transition from canonical to
      specialized nucleosomes in interacting with centromere protein complexes. The
      satisfactory agreement between the results obtained from theoretical and
      experimental methods shows that sequence-dependent centromeric DNA elasticity has
      a main role in nucleosome thermodynamic stability and positioning.

PMID- 12050009
TI  - The mass transfer process and the growth rate of protein crystals.
AB  - In this paper, protein crystal growth is studied by a Mach-Zehnder interferometer
      and an image process system. The interference fringe images are recorded during
      the crystallization of tetragonal hen egg white lysozyme crystal. Concentration
      distributions of the protein solution are given from the interference fringe
      images recorded by the Mach-Zehnder interferometer with a real time servo system
      of a four-step phase shift. The mass transfer flux and the crystal growth rates
      are obtained from the concentration distribution. The results show that the
      observed rates are in accordance with those demonstrated by measurements of the
      experimental images; therefore the method for determining growth rate by the
      diffusion process is reasonable.

PMID- 12050011
TI  - Coherent and robust modulation of a metabolic network by cytoskeletal
      organization and dynamics.
AB  - In order to investigate the influence of cytoskeletal organization and dynamics
      on cellular biochemistry, a mathematical model was formulated based on our own
      experimental evidence. The model couples microtubular protein (MTP) dynamics to
      the glycolytic pathway and its branches: the Krebs cycle, ethanolic fermentation,
      and the pentose phosphate (PP) pathway. Results show that the flux through
      glycolysis coherently and coordinately increases or decreases with increased or
      decreased levels of polymerized MTP, respectively. The rates of individual
      enzymatic steps and metabolite concentrations change with the polymeric status of
      MTP throughout the metabolic network. Negative control is exerted by the PP
      pathway on the glycolytic flux, and the extent of inhibition depends inversely on
      the polymerization state of MTP, i.e. a high degree of polymerization relieves
      the negative control. The stability of the model's steady state dynamics for a
      wide range of variation of metabolic parameters increased with the degree of
      polymerized MTP. The findings indicate that the organization of the cytoskeleton
      bestows coherence and robustness to the coordination of cellular metabolism.

PMID- 12050010
TI  - Fluorescence and nucleic acid binding properties of bovine leukemia virus
      nucleocapsid protein.
AB  - We used the intrinsic fluorescence of bovine leukemia virus p12, a nucleocapsid
      protein with two tryptophan-containing zinc fingers (ZFs), to study its
      conformation and binding to single-stranded nucleic acids. Spectral emission
      maxima suggested solvent-exposed tryptophans. A peptide derived from ZF1 had a
      higher quantum yield and longer average lifetime (tau) than ZF2. BLV p12 tau and
      rotational correlation time were greater than ZF values, but all de-metallated
      sequences gave similar results. Apo p12 showed reduced fluorescence intensity,
      tau and loss of secondary structure. DNA-binding affinity of p12 was in the
      nanomolar range, and decreased 14-fold after Zn++ ejection. Nucleobase preference
      of BLV p12 was different from the closely related HTLV-1 but similar to HIV-1 and
      SIV nucleocapsids, both phylogenetically distant.

PMID- 12050012
TI  - The thermal stability of RNA duplexes containing modified base pairs placed at
      internal and terminal positions of the oligoribonucleotides.
AB  - The presence of various modifications within oligomers changes their
      thermodynamic stability. To get more systematic data, we measured effects of 5-
      and 6-substituted uridine on thermal stability of (AUCU(Mod.)AGAU)2 and
      (AUCUAGAU(Mod.))2. Collected results lead to the following conclusions: (i) 5
      halogenated and 5-alkylated substituents of the uridine affect thermal stability
      of the RNA duplexes differently. Moreover, the 5-fluorouridine changes stability
      of the RNA duplexes opposite to remaining 5-halogenouridines; (ii) for oligomers
      containing 5-chloro, 5-bromo or 5-iodouridine stronger hydrogen bond formed
      between oxygen-4 of the 5-halogenated uracil and 6-amino group of the adenine is
      presumably responsible for stabilizing effect; (iii) placing of A-U(5R) base
      pairs closer to the end of the duplex enhance thermal stability relatively to
      oligomer with central position of this base pair; (iv) the effects of 5
      substituents are additive, particularly for substituents which stabilize RNA
      duplexes; (v) 6-methyluridines (N1 and N3 isomers) as well as 3N-methyluridine
      present at internal position of A-U(Mod.) inhibit duplexes formation; (vi) 6
      methyluridines (N1 and N3 isomers) as well as 3N-methyluridine placed as terminal
      base pairs stabilize the duplexes mostly via 3'-dangling end effect.

PMID- 12050013
TI  - The influence of various modified nucleotides placed as 3'-dangling end on
      thermal stability of RNA duplexes.
AB  - The ribonucleic acids (RNA) form highly folded structures, which behind the
      helical fragments contain several secondary and tertiary structural motives. All
      of them have an influence on thermodynamic stability of the RNA. The 5'- and 3'
      dangling ends are one of those structural motives, which effect stability of the
      adjacent helixes. In this paper, we described the influence of 14 different
      modified nucleotides, placed as 3'-dangling ends, on thermal stability of the RNA
      duplexes. Collected data demonstrate that: (i) 5-substituents of the uridine have
      an impact on the 3'-dangling end effect and the largest changes were observed for
      5-chloro, bromo and methyl substituents; (ii) position of the methyl group within
      the uracil residue affect the thermal stability of the duplex; (iii) increasing a
      size of the heterocycle base placed as the 3'-terminal unpaired nucleotide
      enhances stabilization of duplexes.

PMID- 12050014
TI  - Self-diffusion of polymers in cartilage as studied by pulsed field gradient NMR.
AB  - Pulsed field gradient (PFG) nuclear magnetic resonance (NMR) was used to
      investigate the self-diffusion behaviour of polymers in cartilage. Polyethylene
      glycol and dextran with different molecular weights and in different
      concentrations were used as model compounds to mimic the diffusion behaviour of
      metabolites of cartilage. The polymer self-diffusion depends extremely on the
      observation time: The short-time self-diffusion coefficients (diffusion time
      Delta approximately 15 ms) are subjected to a rather non-specific obstruction
      effect that depends mainly on the molecular weights of the applied polymers as
      well as on the water content of the cartilage. The observed self-diffusion
      coefficients decrease with increasing molecular weights of the polymers and with
      a decreasing water content of the cartilage. In contrast, the long-time self
      diffusion coefficients of the polymers in cartilage (diffusion time Delta
      approximately 600 ms) reflect the structural properties of the tissue.
      Measurements at different water contents, different molecular weights of the
      polymers and varying observation times suggest that primarily the collagenous
      network of cartilage but also the entanglements of the polymer chains themselves
      are responsible for the observed restricted diffusion. Additionally, anomalous
      restricted diffusion was shown to occur already in concentrated polymer
      solutions.

PMID- 12050015
TI  - Cancer and metals and metal compounds: part II--cancer treatment.

PMID- 12050016
TI  - Antimony and bismuth compounds in oncology.
AB  - The main group elements antimony and bismuth are used clinically, primarily for
      the treatment of Leishmaniasis (antimony) and ulcers (bismuth). Despite their
      medicinal efficacy, the exploration of the anti-cancer potential of antimony and
      bismuth compounds is not as well developed as for other metal-containing species.
      The results of cytotoxicity and anti-tumour screening for antimony(III),
      antimony(V) and bismuth(III) compounds are summarised in this review. While this
      is a relatively undeveloped field of research endeavour, promising anti-tumour
      activity has been reported, in particular for bismuth compounds.

PMID- 12050017
TI  - Gold derivatives for the treatment of cancer.
AB  - The cytotoxicity and anti-tumour activity screening trials for both gold(I) and
      gold(III) are summarised. Gold(I) thiolates employed clinically in the treatment
      of rheumatoid arthritis display some potency against various tumours but a
      greater potential is found in their analogues. In particular, analogues featuring
      a linear P-Au-S arrangement in which the thiolate ligand is derived from a
      biologically active thiol display high potency. Further, targeting mitochondria
      with tetrahedrally coordinated gold(I) phosphine compounds with enhanced
      hydrophilicity is a research direction with exciting potential. Recent research
      has shown that gold(III) compounds featuring square-planar geometries, as found
      in cisplatin, may target DNA and may provide new anti-tumour agents.

PMID- 12050018
TI  - Vanadium in cancer treatment.
AB  - Vanadium compounds exert preventive effects against chemical carcinogenesis on
      animals, by modifying, mainly, various xenobiotic enzymes, inhibiting, thus,
      carcinogen-derived active metabolites. Studies on various cell lines reveal that
      vanadium exerts its antitumor effects through inhibition of cellular tyrosine
      phosphatases and/or activation of tyrosine phosphorylases. Both effects activate
      signal transduction pathways leading either to apoptosis and/or to activation of
      tumor suppressor genes. Furthermore, vanadium compounds may induce cell-cycle
      arrest and/or cytotoxic effects through DNA cleavage and fragmentation and plasma
      membrane lipoperoxidation. Reactive oxygen species generated by Fenton-like
      reactions and/or during the intracellular reduction of V(V) to V(IV) by, mainly,
      NADPH, participate to the majority of the vanadium-induced intracellular events.
      Vanadium may also exert inhibitory effects on cancer cell metastatic potential
      through modulation of cellular adhesive molecules, and reverse antineoplastic
      drug resistance. It also possesses low toxicity that, in combination with the
      synthesis of new, more potent and better tolerated complexes, may establish
      vanadium as an effective non-platinum, metal antitumor agent.

PMID- 12050019
TI  - Iron chelators as therapeutic agents for the treatment of cancer.
AB  - A wide variety of studies in vitro, in vivo, and in clinical trials have
      demonstrated that the chelator currently used to treat iron overload disease,
      desferrioxamine, has anti-proliferative effects against both leukemia and
      neuroblastoma. However, the efficacy of desferrioxamine is severely limited due
      to its poor ability to permeate cell membranes and chelate intracellular iron
      pools. These studies have led to the development of other iron chelators that are
      far more effective than desferrioxamine. Some of these chelators such as 3
      aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) have entered phase I
      clinical trials, while other chelators such as 2-hydroxy-1-naphthylaldehyde
      isonicotinoyl hydrazone or tachpyridine require evaluation in animal models. The
      high anti-tumor activity observed with these ligands certainly suggests further
      development of chelators as anti-cancer agents is warranted.

PMID- 12050020
TI  - Gallium in cancer treatment.
AB  - Gallium (Ga) is the second metal ion, after platinum, to be used in cancer
      treatment. Its activities are numerous and various. It modifies three-dimensional
      structure of DNA and inhibits its synthesis, modulates protein synthesis,
      inhibits the activity of a number of enzymes, such as ATPases, DNA polymerases,
      ribonucleotide reductase and tyrosine-specific protein phosphatase. Ga alters
      plasma membrane permeability and mitochondrial functions. Ga salts are taken up
      more efficiently and more specifically by tumour cells when orally administered.
      New compounds have been prepared: Ga maltolate, doxorubicin-Ga-transferrin
      conjugate and Tris(8-quinolinolato)Ga(III), which show interesting activities. Ga
      toxicity is well documented in vitro and in vivo in animals. In humans, the oral
      administration Ga is less toxic, and allows a chronic treatment, allowing an
      improvement of its bioavailability in tumours, by comparison with the parenteral
      use. The anticancer activity of Ga salts has been demonstrated but other effects
      have also been noted such as many bone effects that could be useful in bone
      metastatic patients. Its has also been shown that a long period of administration
      could induce tumour fibrosis. Ga is synergistic with other anticancer drugs.
      Although not as potent as platinum in vitro, the anticancer activity of Ga should
      not be ignored, but the schedule of administration still needs to be optimised
      and new compounds are now under clinical investigations.

PMID- 12050021
TI  - Rhodium and its compounds as potential agents in cancer treatment.
AB  - The antitumor activity of the inorganic complex cis-diammine-dichloroplatinum(II)
      (cisplatin) led to the development of other types of non-organic cytostatic
      drugs. Numerous platinum other platinum and non-platinum metal compounds were
      shown to be effective against animal model tumors as well as tumors in man.
      However, the introduction of novel transition metal agents in clinical treatment
      is exceptionally slow. So far, Ru(II) and Ru(III) complexes have shown very
      promising properties while the Ru(III) compound, [ImH][trans
      Cl4(Me2SO)(Im)Ru(III)] (Im=imidazole, NAMI-A), is the first ruthenium compound
      that successfully entered phase I clinical trials. Rhodium belongs to the same
      group as platinum and ruthenium. However, rhodium compounds, analogues to the
      corresponding platinum and ruthenium compounds that possess significant antitumor
      properties, were found to be less effective as anticancer agents mainly due to
      their toxic effects. Dimeric mu-Acetato dimers of Rh(II) as well as monomeric
      square planar Rh(I) and octahedral Rh(III) complexes have shown interesting
      antitumor properties.

PMID- 12050022
TI  - Titanium complexes in cancer treatment.
AB  - A series of complexes containing titanium, Ti, as a metal center has shown to
      possess a wide spectrum of antitumor properties. This series belongs to the non
      platinum metal antitumor agents which has been developed mainly in the past 20
      years. The bis(beta-diketonato)titanium(IV) and titanocene derivatives appear to
      offer a different alternative for cancer chemotherapy which do not follow the
      rationale and mechanism of action of the platinum complexes. The hydrolysis of
      these complexes in aqueous and pseudo aqueous solutions is discussed and the
      interaction studies of titanium complexes with biomolecules are also presented to
      unravel the mechanism of action at molecular levels.

PMID- 12050023
TI  - Particular aspects of platinum compounds used at present in cancer treatment.
AB  - The history of platinum in cancer treatment began 150 years ago with the first
      synthesis of cisplatin; but it was not used in the clinic before 30 years ago.
      Then 3000 derivatives were synthesised and tested, with poor successes: three
      other derivatives only are available today. Clearly they are not more active, but
      they are less toxic than cisplatin, although two, carboplatin and nedaplatin,
      yield a cross-resistance, while one, oxaliplatin, does not. Their mechanisms of
      action are similar: these four pro-drugs form adducts with DNA, impairing DNA
      synthesis and repair then. Their pharmacokinetics are complicated since we always
      measure two overlapping pharmacokinetics: those of the parent compound and of the
      bound platinum. Cisplatin is now recommended for few cancers, it is replaced by
      less-toxic carboplatin, and therefore more easily used in combination.
      Oxaliplatin give interesting results in a number of cancers. The official
      recommendation in Japan for nedaplatin is head and neck, testicular, lung,
      oesophageal, ovarian, and cervical cancer.

PMID- 12050024
TI  - [Abstracts of the XXII Cancer Meeting. 4-6 June 2002, Paris, France. ].

PMID- 12050039
TI  - [Does the impact factor the single suitable criteria to judge the quality of a
      scientific paper?].

PMID- 12050040
TI  - [The divine quality].

PMID- 12050041
TI  - [Biomarkers of tobacco smoke exposure].
AB  - Tobacco smoking is a major risk factor for cancer, cardiovascular diseases and
      respiratory illnesses. Smoking is increasing among children and adolescents with
      subsequent consequences on the health. Furthermore, maternal tobacco smoking
      during pregnancy adversely affects prenatal growth. Nicotine, the most important
      tobacco alkaloid, is responsible for maintaining tobacco addiction. According to
      a recent Circulaire de la direction generale de la sante, nicotine dependence
      should be determined through questionnaires and quantitative estimate of nicotine
      metabolites. Nicotine blood level fluctuates and urinary nicotine excretion is of
      short duration. Nicotine is intensively metabolized in the liver and oxidized
      into cotinine. Urinary measurement of cotinine appears to be highly related with
      the degree of intoxication and to allow the differentiation between non exposed
      and exposed non-smokers. In order to check the present application of nicotine
      metabolites measurement, a survey was conducted in 340 smoking cessation units.
      Forty percent physicians (n = 137) answered the survey. For 17% of them, the
      quantification of nicotine metabolites is included in their daily practise and
      for 79%, guidelines about cotinine measurement should be given in France. Sixty
      seven biologists answered the survey. Recommendations for immunoassay and HPLC
      determination of cotinine should be given as reported by 66 and 44% of them
      respectively. Indeed, urinary cotinine measurement with high performance liquid
      chromatography is highly sensitive and specific. However, immunoassays are more
      convenient. These two approaches are presently under investigation in order to
      provide guidelines for optimal use in various clinical situations. Traditional
      measures for nicotine dependence are the number of cigarettes smoked per day,
      nicotine intake expressed as mg per day, Fagerstr m questionnaire, expired air
      carbon monoxide, thiocyanates and cotinine levels in biological fluids. Urinary
      cotinine measurement is the most useful for the follow-up of smoking cessation
      including adjustment of nicotine replacement therapy, especially after a clinical
      event or for the follow-up of smoking pregnant women. It allows the detection of
      passive smoke exposure in children who are hospitalized for recurrent respiratory
      illnesses.

PMID- 12050042
TI  - [Persistent polyclonal B-cell lymphocytosis].
AB  - Persistent polyclonal B-cell lymphocytosis (PPBL) is a rare and recently
      described entity. PPBL is diagnosed predominantly but not exclusively in women,
      usually smokers and is characterized by a moderate, chronic and absolute
      lymphocytosis (> 4 x 109/L). Peripheral blood examination show in all cases
      atypical binucleated lymphocytes. A polyclonal serum IgM is also associated and
      HLA-DR7 expression is present in most cases. The B cells are polyclonal with
      kappa and lambda light-chain expression. No clonal rearrangement of
      immunoglobulin heavy chain genes is observed. Finally, +i(3q) is a recurrent
      chromosomal abnormality and detected in 77% of cases with premature chromosome
      condensation in 50% and both abnormalities in 41% of cases. The benign clinical
      course of PPBL and lack of biological evolution in the majority of cases suggest
      that recognition is so important that aggressive therapy could be avoided.

PMID- 12050043
TI  - [Enzyme calibrators: principle and practical use].
AB  - Results of catalytic activities of enzymes are highly dependent on the
      measurement procedures and on local conditions. Thus, only poorly marked
      improvement of interlaboratory comparability of results have been observed in
      clinical enzymology. To solve this problem, SFBC and IFCC have proposed to use
      "validated enzyme calibrators". Standardised operating procedures adapted to 37 
      C have been developed by IFCC for the most commonly used enzymes in clinical
      chemistry, and will be soon published. Reference materials which have been
      certified with these SOPs can be used as calibrators for a set of measurement
      methods which exhibit the same analytical specificity. Calibrators must be
      commutable, a property that must be checked experimentally. It is possible to
      produce stable and commutable materials for the calibration of a set of methods.
      Interest of this approach has been demonstrated for several enzymes. Results of
      two studies presented here show that the comparison of results to the upper limit
      of reference ranges does not improve the interlaboratory comparability of results
      in contrast to the calibration of different methods by a common calibrator which
      allowed to reach an interlaboratory CV close to 4% for ALT and gammaGT.

PMID- 12050045
TI  - [A biological bank in an epidemiologic study in France: How? Example of the E3N
      EPIC study].
AB  - The organisation of a bank of biological material as part of an epidemiologic
      study raises a number of problems. The first part of the paper discusses, in the
      context of the French regulation, the legal obligations, the administrative
      problems, the locations selected for the biological sampling, the strategy for
      sending out invitations to the participants, and the logistic of biological
      samples transport and storage. The second part presents the solutions brought to
      these problems in the prospective E3N-EPIC cohort study.

PMID- 12050044
TI  - [Antiphosphoplipid antibodies and retinal occlusive vasculopathy].
AB  - PURPOSE: to determine the prevalence of antiphospholipid antibodies in patients
      with occlusive retinal vascular events, exempt from conventional risk factors of
      retinal thrombosis. METHODS: eleven patients with retinal vascular occlusion,
      free of main accepted risk factors for retinal thrombosis, were retrospectively
      screened for antiphospholipid antibodies (anticardiolipin and anti-beta2
      glycoprotein 1 antibodies) by an Elisa method. Prevalence of antiphospholipid
      antibodies were compared with those in a homogenous control group of 100
      patients. RESULTS: the prevalence of antiphospholipid antibodies in the study
      group was 27% (three of 11). Comparison with control group prevalence (3%) showed
      a statistically significant difference (p < 0,001). One patient in the study
      disclosed positivity for IgG anticardiolipine antibodies, one for IgM
      anticardiolipine antibodies and one for anti-beta2 glycoprotein 1 antibodies.
      CONCLUSION: our results lead us to recommend a systematic search for specific
      antiphospholipid antibodies in such young patients which could have an importance
      for the diagnosis of primary antiphospholipid syndrome.

PMID- 12050047
TI  - [Sensitivity of HIV infection screening assays in 2001].
AB  - Early detection of human immunodeficiency virus (HIV) infection is critical for
      clinical diagnosis and treatment of patients, as well as for ensuring the safety
      of blood products. Recently, fourth-generation HIV screening assays have been
      developed with the objective to offer an increased sensitivity by combining
      detection of anti-HIV antibodies (Ab) with detection of the p24 viral antigen
      (Ag). Eight different HIV assays commercially available in France (five fourth
      generation HIV screening assays and three third-generation HIV Ab-only assays)
      were compared in a broad number of seroconversion panels (n = 27). This extensive
      analysis highlights: 1) the importance of p24 Ag detection for early diagnosis;
      2) the improved sensitivity of fourth-generation assays over Ab-only tests. In
      conclusion, these results emphasize the detection limitations of the different
      assays and suggest improvements for future HIV screening assays.

PMID- 12050046
TI  - [Modification of breath sample alcohol level kinetics resulting from the
      association of citric acid and fructose].
AB  - To show the effect, before the ingestion of alcohol, of orally absorbing a
      concentrated aqueous solution of fructose and citric acid (SACF) upon the
      kinetics of breath sample alcohol levels (BSAL) in a young, healthy, male
      volunteer. METHODS: 14 volunteers consumed alcohol after an overnight fast in the
      form of whisky 0.49 g/kg body weight. The BSAL were determined between 0 and 150
      minutes after ingestion of alcohol. For each volunteer two trials were carried
      out, one 5 minutes after the ingestion of 50 mL of water, and one 5 minutes after
      the ingestion of 50 mL of SCAF. The differents kinetics of the BSAL of the two
      trials were compared. RESULTS: each time the measurements of BSAL with SCAF was
      inferior to that without SACF (p < 0.002). The Cmax with SCAF was inferior (by
      about 35%) to that without SCAF (p < 0.001). The Tmax with SCAF was about twice
      that without SACF (p < 0.001). There was no significant difference in the speed
      of decrease in BSAL. CONCLUSION: for the level of consumption of alcohol tested
      the SCAF allows the rise in BSAL to be limited (and delayed). The article
      discusses the reasons for this action, essentially caused by a slowing down of
      gastric emptying resulting from the citric acid. The latter also allows, in this
      way, an increase in the effect of the first gastric passage of ethanol.

PMID- 12050048
TI  - [Determination of total plasma homocysteine: preanalytical parameters, method
      comparison and interchangeability].

PMID- 12050050
TI  - [Place of homocysteinemia in the treatment and the follow-up of lower-limb
      artherosclerotic disease].

PMID- 12050049
TI  - [Homocysteinemia and recurrent fetal losses: description of three cases].

PMID- 12050051
TI  - [Guidelines for the diagnosis and monitoring of thyroid disease].

PMID- 12050052
TI  - [Biochemical markers of bone turnover: preanalytical variability and
      recommendations for use].

PMID- 12050053
TI  - [Biochemical markers of bone turnover: clinical interpretation in osteoporosis].

PMID- 12050054
TI  - [Guidelines for human gene nomenclature].
AB  - As given the abundance of information on the human genome which as accumulated
      over the two past decades, the necessity of harmonizing the rules of nomenclature
      for human genes and mutations has become a demand of the scientific community.
      Indeed, the estimated number of human genes is about 35,000, and the number of
      mutations might be of the order of several millions. The purpose of this article
      is to present the recommendations for human gene nomenclature published by the
      HGNC (human gene nomenclature committee), as well as the main databases in which
      the reader may find or check the correct denomination of a human gene or
      mutation.

PMID- 12050055
TI  - [Assessment of the agreement between three automated hematology instruments].

PMID- 12050057
TI  - [Determination of specific proteins...in the balance].

PMID- 12050058
TI  - [Let us look for unity: dream or reality].

PMID- 12050059
TI  - Information concept in biology.

PMID- 12050060
TI  - A heuristic managing errors for DNA sequencing.
AB  - MOTIVATION: A new heuristic algorithm for solving DNA sequencing by hybridization
      problem with positive and negative errors. RESULTS: A heuristic algorithm
      providing better solutions than algorithms known from the literature based on
      tabu search method.

PMID- 12050061
TI  - PGAAS: a prokaryotic genome assembly assistant system.
AB  - MOTIVATION: In order to accelerate the finishing phase of genome assembly,
      especially for the whole genome shotgun approach of prokaryotic species, we have
      developed a software package designated prokaryotic genome assembly assistant
      system (PGAAS). The approach upon which PGAAS is based is to confirm the order of
      contigs and fill gaps between contigs through peptide links obtained by searching
      each contig end with BLASTX against protein databases. RESULTS: We used the
      contig dataset of the cyanobacterium Synechococcus sp. strain PCC7002 (PCC7002),
      which was sequenced with six-fold coverage and assembled using the Phrap package.
      The subject database is the protein database of the cyanobacterium, Synechocystis
      sp. strain PCC6803 (PCC6803). We found more than 100 non-redundant peptide
      segments which can link at least 2 contigs. We tested one pair of linked contigs
      by sequencing and obtained satisfactory result. PGAAS provides a graphic user
      interface to show the bridge peptides and pier contigs. We integrated Primer3
      into our package to design PCR primers at the adjacent ends of the pier contigs.
      AVAILABILITY: We tested PGAAS on a Linux (Redhat 6.2) PC machine. It is developed
      with free software (MySQL, PHP and Apache). The whole package is distributed
      freely and can be downloaded as UNIX compress file:
      ftp://ftp.cbi.pku.edu.cn/pub/software/unix/pgaas1.0.tar.gz. The package is being
      continually updated.

PMID- 12050062
TI  - The generation of long telomere overhangs in human cells: a model and its
      implication.
AB  - MOTIVATION: Linear chromosomes carry on both ends repetitive DNA sequences called
      telomere. In the conventional model of semi-conservative DNA replication, the 3'
      end of a linear DNA strand cannot be fully replicated, resulting in a single
      stranded 3' overhang at one end of the double-stranded DNA product. In this
      model, the length of the overhang is expected to be about the size of an RNA
      primer (about nine nucleotides for human cells). However, it has been found that
      the telomere overhangs in human cells can be as long as several hundred
      nucleotides. At present, the opinion regarding how such long overhangs are
      produced is controversial. RESULTS: In order to gain insight into the mechanism
      by which long telomere overhangs are produced, we derived a mathematical model
      that can perfectly describe the length distribution of telomere overhangs in
      several human cell strains. The model suggests that the production of telomere
      overhangs can be explained by three contributions corresponding to three regions
      on the G-rich telomere template strand, namely, the region occupied by the last
      primer, that missed out by this primer at its 5'-side and the 3'-terminus of the
      template strand that is inaccessible to primase. The model can also be used to
      simulate incomplete telomere replication.

PMID- 12050064
TI  - Sequence complexity profiles of prokaryotic genomic sequences: a fast algorithm
      for calculating linguistic complexity.
AB  - MOTIVATION: One of the major features of genomic DNA sequences, distinguishing
      them from texts in most spoken or artificial languages, is their high
      repetitiveness. Variation in the repetitiveness of genomic texts reflects the
      presence and density of different biologically important messages. Thus,
      deviation from an expected number of repeats in both directions indicates a
      possible presence of a biological signal. Linguistic complexity corresponds to
      repetitiveness of a genomic text, and potential regulatory sites may be
      discovered through construction of typical patterns of complexity distribution.
      RESULTS: We developed software for fast calculation of linguistic sequence
      complexity of DNA sequences. Our program utilizes suffix trees to compute the
      number of subwords present in genomic sequences, thereby allowing calculation of
      linguistic complexity in time linear in genome size. The measure of linguistic
      complexity was applied to the complete genome of Haemophilus influenzae. Maps of
      complexity along the entire genome were obtained using sliding windows of 40,
      100, and 2000 nucleotides. This approach provided an efficient way to detect
      simple sequence repeats in this genome. In addition, local profiles of complexity
      distribution around the starts of translation were constructed for 21 complete
      prokaryotic genomes. We hypothesize that complexity profiles correspond to
      evolutionary relationships between organisms. We found principal differences in
      profiles of the GC-rich and other (non-GC-rich) genomes. We also found
      characteristic differences in profiles of AT genomes, which probably reflect
      individual species variations in translational regulation. AVAILABILITY: The
      program is available upon request from Alexander Bolshoy or at
      http://csweb.haifa.ac.il/library/#complex.

PMID- 12050063
TI  - Detecting cryptically simple protein sequences using the SIMPLE algorithm.
AB  - MOTIVATION: Low-complexity or cryptically simple sequences are widespread in
      protein sequences but their evolution and function are poorly understood. To date
      methods for the detection of low complexity in proteins have been directed
      towards the filtering of such regions prior to sequence homology searches but not
      to the analysis of the regions per se. However, many of these regions are encoded
      by non-repetitive DNA sequences and may therefore result from selection acting on
      protein structure and/or function. RESULTS: We have developed a new tool, based
      on the SIMPLE algorithm, that facilitates the quantification of the amount of
      simple sequence in proteins and determines the type of short motifs that show
      clustering above a certain threshold. By modifying the sensitivity of the program
      simple sequence content can be studied at various levels, from highly organised
      tandem structures to complex combinations of repeats. We compare the relative
      amount of simplicity in different functional groups of yeast proteins and
      determine the level of clustering of the different amino acids in these proteins.
      AVAILABILITY: The program is available on request or online at
      http://www.biochem.ucl.ac.uk/bsm/SIMPLE.

PMID- 12050065
TI  - Support vector machines with selective kernel scaling for protein classification
      and identification of key amino acid positions.
AB  - MOTIVATION: Data that characterize primary and tertiary structures of proteins
      are now accumulating at a rapid and accelerating rate and require automated
      computational tools to extract critical information relating amino acid changes
      with the spectrum of functionally attributes exhibited by a protein. We propose
      that immunoglobulin-type beta-domains, which are found in approximate 400
      functionally distinct forms in humans alone, provide the immense genetic
      variation within limited conformational changes that might facilitate the
      development of new computational tools. As an initial step, we describe here an
      approach based on Support Vector Machine (SVM) technology to identify amino acid
      variations that contribute to the functional attribute of pathological self
      assembly by some human antibody light chains produced during plasma cell
      diseases. RESULTS: We demonstrate that SVMs with selective kernel scaling are an
      effective tool in discriminating between benign and pathologic human
      immunoglobulin light chains. Initial results compare favorably against manual
      classification performed by experts and indicate the capability of SVMs to
      capture the underlying structure of the data. The data set consists of 70
      proteins of human antibody kappa1 light chains, each represented by aligned
      sequences of 120 amino acids. We perform feature selection based on a first-order
      adaptive scaling algorithm, which confirms the importance of changes in certain
      amino acid positions and identifies other positions that are key in the
      characterization of protein function.

PMID- 12050066
TI  - Characterization of the folding degree of proteins.
AB  - MOTIVATION: The characterization of the folding degree of chains is central to
      the elucidation of structure--function relationships in proteins. Here we present
      a new index for characterizing the folding degree of a (protein) chain. This
      index shows a range of features that are desirable for the study of the relation
      between structure and function in proteins. RESULTS: A novel index characterizing
      the folding degree of (protein) chains is developed based on the spectral moments
      of a matrix representing the dihedral angles (phi, omega and epsilon) of the
      protein main chain. The proposed index is normalized to the chain size, is not
      correlated to the gyration radius of the backbone chain and is able to
      distinguish between structures for which the sum of the main-chain dihedral
      angles is identical. The index is well correlated to the percentages of helix and
      strand in proteins, shows a linear dependence with temperature changes, and is
      able to differentiate among protein families. AVAILABILITY: On request from the
      author.

PMID- 12050067
TI  - Extraction of knowledge on protein-protein interaction by association rule
      discovery.
AB  - MOTIVATION: Protein-protein interactions are systematically examined using the
      yeast two-hybrid method. Consequently, a lot of protein-protein interaction data
      are currently being accumulated. Nevertheless, general information or knowledge
      on protein-protein interactions is poorly extracted from these data. Thus we have
      been trying to extract the knowledge from the protein-protein interaction data
      using data mining. RESULTS: A data mining method is proposed to discover
      association rules related to protein-protein interactions. To evaluate the
      detected rules by the method, a new scoring measure of the rules is introduced.
      The method allowed us to detect popular interaction rules such as "An SH3 domain
      binds to a proline-rich region." These results indicate that the method may
      detect novel knowledge on protein-protein interactions.

PMID- 12050068
TI  - Evaluation of computational metabolic-pathway predictions for Helicobacter
      pylori.
AB  - MOTIVATION: We seek to determine the accuracy of computational methods for
      predicting metabolic pathways in sequenced genomes, and to understand the
      contributions of both the prediction algorithms, and the reference pathway
      databases used by those algorithms, to the prediction accuracy. RESULTS: The
      comparisons we performed were as follows. (1) We compared two predictions of the
      pathway complements of Helicobacter pylori that were computed by an early version
      of our pathway-prediction algorithm: prediction A used the EcoCyc E. coli pathway
      DB as the reference database (DB) for prediction, and prediction B used the
      MetaCyc pathway DB (a superset of EcoCyc) as the reference pathway DB. The
      MetaCyc-based prediction contained 75% more pathway predictions, but we believe a
      significant number of those predictions were false positives. (2) We compared two
      predictions of the pathway complement of H. pylori that used MetaCyc as the
      reference pathway DB, but that used different algorithms: the original PathoLogic
      algorithm, and an enhanced version of the algorithm designed to eliminate false
      positive pathway predictions. The improved algorithm predicted 30?% fewer
      metabolic pathways than the original algorithm; all of the eliminated pathways
      are believed to be false-positive predictions. (3) We compared the 98 pathways
      predicted by the enhanced algorithm with the results of a manual analysis of the
      pathways of H. pylori. Results: 40 of the computationally predicted pathways were
      consistent with the manual analysis, 13 pathways are considered false-positive
      predictions, and four pathways had partially overlapping topologies. Twenty-six
      predicted pathways were not mentioned in the manual analysis; we believe these
      are correct predictions by PathoLogic that were not found by the manual analysis.
      Five pathways from the manual analysis were not found computationally. Agreement
      between the computational and manual predictions was good overall, with the
      computational analysis inferring many pathways that the manual analysis did not
      identify. Ultimately the manual analysis is also partially speculative, and
      therefore is not an absolute measure of correctness. The algorithm is designed to
      err on the side of more false positives to bring more potential pathways to the
      user's attention. The resulting H. pylori pathway DB is freely available at
      http://ecocyc.org:1555/HPY/organism-summary?object=HPY. AVAILABILITY: The Pathway
      Tools software is freely available to academic users, and is available to
      commercial users for a fee. Contact pkarp@ai.sri.com for information on obtaining
      the software.

PMID- 12050069
TI  - Identifying good diagnostic gene groups from gene expression profiles using the
      concept of emerging patterns.
AB  - MOTIVATIONS AND RESULTS: Gene groups that are significantly related to a disease
      can be detected by conducting a series of gene expression experiments. This work
      is aimed at discovering special types of gene groups that satisfy the following
      property. In each group, its member genes are found to be one-to-one contained in
      pre-determined intervals of gene expression level with a large frequency in one
      class of cells but are never found unanimously in these intervals in the other
      class of cells. We call these gene groups emerging patterns, to emphasize the
      patterns' frequency changes between two classes of cells. We use effective
      discretization and gene selection methods to obtain the most discriminatory
      genes. We also use efficient algorithms to derive the patterns from these genes.
      According to our studies on the ALL/AML dataset and the colon tumor dataset, some
      patterns, which consist of one or more genes, can reach a high frequency of 90%,
      or even 100%. In other words, they nearly or fully dominate one class of cells,
      even though they rarely occur in the other class. The discovered patterns are
      used to classify new cells with a higher accuracy than other reported methods.
      Based on these patterns, we also conjecture the possibility of a personalized
      treatment plan which converts colon tumor cells into normal cells by modulating
      the expression levels of a few genes.

PMID- 12050070
TI  - Adaptive quality-based clustering of gene expression profiles.
AB  - MOTIVATION: Microarray experiments generate a considerable amount of data, which
      analyzed properly help us gain a huge amount of biologically relevant information
      about the global cellular behaviour. Clustering (grouping genes with similar
      expression profiles) is one of the first steps in data analysis of high
      throughput expression measurements. A number of clustering algorithms have proved
      useful to make sense of such data. These classical algorithms, though useful,
      suffer from several drawbacks (e.g. they require the predefinition of arbitrary
      parameters like the number of clusters; they force every gene into a cluster
      despite a low correlation with other cluster members). In the following we
      describe a novel adaptive quality-based clustering algorithm that tackles some of
      these drawbacks. RESULTS: We propose a heuristic iterative two-step algorithm:
      First, we find in the high-dimensional representation of the data a sphere where
      the "density" of expression profiles is locally maximal (based on a preliminary
      estimate of the radius of the cluster-quality-based approach). In a second step,
      we derive an optimal radius of the cluster (adaptive approach) so that only the
      significantly coexpressed genes are included in the cluster. This estimation is
      achieved by fitting a model to the data using an EM-algorithm. By inferring the
      radius from the data itself, the biologist is freed from finding an optimal value
      for this radius by trial-and-error. The computational complexity of this method
      is approximately linear in the number of gene expression profiles in the data
      set. Finally, our method is successfully validated using existing data sets.
      AVAILABILITY: http://www.esat.kuleuven.ac.be/~thijs/Work/Clustering.html

PMID- 12050071
TI  - Unsupervised technique for robust target separation and analysis of DNA
      microarray spots through adaptive pixel clustering.
AB  - MOTIVATION: Microarray images challenge existing analytical methods in many ways
      given that gene spots are often comprised of characteristic imperfections.
      Irregular contours, donut shapes, artifacts, and low or heterogeneous expression
      impair corresponding values for red and green intensities as well as their ratio
      R/G. New approaches are needed to ensure accurate data extraction from these
      images. RESULTS: Herein we introduce a novel method for intensity assessment of
      gene spots. The technique is based on clustering pixels of a target area into
      foreground and background. For this purpose we implemented two clustering
      algorithms derived from k-means and Partitioning Around Medoids (PAM),
      respectively. Results from the analysis of real gene spots indicate that our
      approach performs superior to other existing analytical methods. This is
      particularly true for spots generally considered as problematic due to
      imperfections or almost absent expression. Both PX(PAM) and PX(KMEANS) prove to
      be highly robust against various types of artifacts through adaptive
      partitioning, which more correctly assesses expression intensity values.
      AVAILABILITY: The implementation of this method is a combination of two
      complementary tools Extractiff (Java) and Pixclust (free statistical language R),
      which are available upon request from the authors.

PMID- 12050072
TI  - Xdigitise: visualization of hybridization experiments.
AB  - Xdigitise is a software system for visualization of hybridization experiments
      giving the user facilities to analyze the corresponding images manually or
      automatically. Images of the high-density DNA arrays are displayed as well as the
      results of an external image analysis bundled with Xdigitise, e.g. the spot
      locations are marked and the duplicate correlations are shown by a color scale.
      AVAILABILITY: Xdigitise can be downloaded from
      http://www.molgen.mpg.de/~xdigitise.

PMID- 12050073
TI  - Gene structure identification with MyGV using cDNA evidence and protein homologs
      to improve ab initio predictions.
AB  - MyGV is an application to visualize (potentially genome-scale) gene structure
      annotation and prediction. The output of any external gene prediction program can
      be easily converted to a generalized format for input into MyGV. The application
      displays all input simultaneously in graphical representation, with a toggle
      option for a text-based view. Zooming capabilities allow detailed comparisons for
      specific genome locations. The tool is particularly helpful for refinement of ab
      initio predicted gene structures by spliced alignment with cDNA or protein
      homologs. AVAILABILITY: The program was written in Java and is freely available
      to non-commercial users by electronic download from
      http://bioinformatics.iastate.edu/bioinformatics2go/MyGV.

PMID- 12050074
TI  - EMBL-Align: a new public nucleotide and amino acid multiple sequence alignment
      database.
AB  - The submission of multiple sequence alignment data to EMBL has grown 30-fold in
      the past 10 years, creating a problem of archiving them. The EBI has developed a
      new public database of multiple sequence alignments called EMBL-Align. It has a
      dedicated web-based submission tool, Webin-Align. Together they represent a
      comprehensive data management solution for alignment data. Webin-Align accepts
      all the common alignment formats and can display data in CLUSTALW format as well
      as a new standard EMBL-Align flat file format. The alignments are stored in the
      EMBL-Align database and can be queried from the EBI SRS (Sequence Retrieval
      System) server. AVAILABILITY: Webin-Align:
      http://www.ebi.ac.uk/embl/Submission/align_top.html, EMBL-Align:
      ftp://ftp.ebi.ac.uk/pub/databases/embl/align, http://srs.ebi.ac.uk/

PMID- 12050075
TI  - BeoBLAST: distributed BLAST and PSI-BLAST on a Beowulf cluster.
AB  - BeoBLAST is an integrated software package that handles user requests and
      distributes BLAST and PSI-BLAST searches to nodes of a Beowulf cluster, thus
      providing a simple way to implement a scalable BLAST system on top of relatively
      inexpensive computer clusters. Additionally, BeoBLAST offers a number of novel
      search features through its web interface, including the ability to perform
      simultaneous searches of multiple databases with multiple queries, and the
      ability to start a search using the PSSM generated from a previous PSI-BLAST
      search on a different database. The underlying system can also handle automated
      querying for high throughput work. AVAILABILITY: Source code is available under
      the GNU public license at http://bioinformatics.fccc.edu/

PMID- 12050076
TI  - ENDscript: a workflow to display sequence and structure information.
AB  - ENDscript is a web server grouping popular programs such as BLAST, Multalin and
      DSSP. It uses as query the co-ordinates file of a protein in Protein Data Bank
      format and generates PostScript and png figures showing: residues conserved after
      a multiple alignment against homologous sequences, secondary structure elements,
      accessibility, hydropathy and intermolecular contacts. Thus, the user can relate
      quickly 1D, 2D and 3D information of a protein of known structure. AVAILABILITY:
      http://genopole.toulouse.inra.fr/ENDscript

PMID- 12050077
TI  - The Sulfinator: predicting tyrosine sulfation sites in protein sequences.
AB  - Protein tyrosine sulfation is an important post-translational modification of
      proteins that go through the secretory pathway. No clear-cut acceptor motif can
      be defined that allows the prediction of tyrosine sulfation sites in polypeptide
      chains. The Sulfinator is a software tool that can be used to predict tyrosine
      sulfation sites in protein sequences with an overall accuracy of 98%. Four
      different Hidden Markov Models were constructed, each of them specialized to
      recognize sulfated tyrosine residues depending on their location within the
      sequence: near the N-terminus, near the C-terminus, in the center of a window
      with a size of at least 25 amino acids, as well as in windows containing several
      tyrosine residues. AVAILABILITY: The Sulfinator is accessible at
      (http://www.expasy.org/tools/sulfinator/). SUPPLEMENTARY INFORMATION: Sulfinator
      documentation is accessible at (http://www.expasy.org/tools/sulfinator/sulfinator
      doc.html).

PMID- 12050078
TI  - GP3: GenePix post-processing program for automated analysis of raw microarray
      data.
AB  - Here we describe an automated and customizable program to correct, filter and
      normalize raw microarray data captured using GenePix, a commonly used microarray
      image analysis application. Files can be processed individually or in batch mode
      for increased throughput. User defined inputs specify the stringency of data
      filtering and the method and conditions of normalization. The output includes
      gene summaries for replicate spots and descriptive statistics for each
      experiment. The source code (Perl) can also be adapted to handle raw data output
      from other image analysis applications. AVAILABILITY:
      http://bch.msu.edu/~zacharet/microarray/GP3.html

PMID- 12050079
TI  - A bioinformatics tool to select sequences for microarray studies of mouse models
      of oncogenesis.
AB  - One of the challenges to the effective utilization of cDNA microarray analysis in
      mouse models of oncogenesis is the choice of a critical set of probes that are
      informative for human disease. Given the thousands of genes with a potential role
      in human oncogenesis and the hundreds of thousands of mouse sequences available
      for use as probes, selection of an informative set of mouse probes can be an
      overwhelming task. We have developed a web based sequence mining tool using
      DataBase Independent (DBI) Perl to annotate publicly available sequences. The
      Mouse Oncochip Design Tool uses the Mouse Genome Database (MGD) developed and
      maintained by the Jackson Laboratories for mouse DNA sequences. There are over
      380 000 sequences in their database. The output list has been ordered to present
      the genes more likely to be informative in a mouse model of human cancer using a
      candidate set of oncogenes to order the list. Mouse sequences that represent
      genes that are homologous with a member of a human oncogene set are listed first.
      In addition it provides a set of links for information on clone source gene
      function. CONTACT: http://nciarray.nci.nih.gov/cgi-bin/me/mouse_design.cgi

PMID- 12050081
TI  - Area MST and heading perception in macaque monkeys.
AB  - The macaque medial superior temporal area (MST) is proposed to be specialized for
      analyzing complex 'optic flow' information. Such space-varying motion patterns
      provide a rich source of information about self motion, scene structure and
      object shape. We report the performance of rhesus macaques on a two-alternative
      'heading' task, in which they reported whether horizontally varying, simulated
      trajectories were to left or right of center. Monkeys were sensitive to small
      heading angles; thresholds averaged 1.5-3 degrees. Heading estimates were stable
      in the face of changing stimulus location and smooth pursuit eye movements. In
      addition, we tested the role of area MST in heading judgements by electrically
      activating columns of neurons in this area while the monkeys performed the
      heading task. Activation of MST frequently affected performance, usually causing
      choice biases. These induced biases were often large and usually concordant with
      the preference of the neurons being activated. In addition, the induced biases
      were often larger in the presence of smooth pursuit eye movements. These results
      favor the hypothesis that MST is involved in recovering self-motion direction
      from optic flow cues and in the process by which heading perception is
      compensated for ongoing eye movements.

PMID- 12050080
TI  - Human-specific organization of primary visual cortex: alternating compartments of
      dense Cat-301 and calbindin immunoreactivity in layer 4A.
AB  - There is evidence that the cortical anatomy of the magnocellular (M) visual
      pathway, which carries information about motion and luminance contrast, was
      modified in human evolution. Recent results indicate that layer 4A of humans
      contains a meshwork of tissue bands that stain densely for nonphosphorylated
      neurofilament (NPNF), a protein that is preferentially expressed in elements of
      the M pathway, whereas apes and monkeys lack a comparable pattern. Here we
      examined the distribution of staining for Cat-301 -- a monoclonal antibody well
      established to stain M-related structures preferentially -- in area V1 of humans,
      apes (chimpanzees, orangutan), Old World monkeys (macaques) and New World monkeys
      (spider monkeys, squirrel monkeys). Single-staining experiments, using a
      peroxidase-tetramethylbenzidine (TMB) reaction, revealed alternating zones of
      dark and light staining for Cat-301 in layer 4A of humans, similar to those
      observed with NPNF. Double-staining studies in humans revealed that Cat-301
      immunoreactive somas and neuropil were localized within the same tissue bands
      that stained strongly for NPNF and, furthermore, that these bands alternated with
      irregularly shaped territories that stained very strongly for calbindin. Nonhuman
      primates, by contrast to humans, displayed weak Cat-301 and calbindin staining in
      layer 4A. The co-localization of Cat-301 and NPNF in human layer 4A, and the weak
      staining for these molecules in layer 4A of other primates, suggests that the
      cortical representation of the M channel was modified in recent human evolution.
      The calbindin-rich compartments in human layer 4A cannot be related to a
      particular geniculostriate pathway on neurochemical grounds; they may constitute
      an interneuronal population that increased in human evolution.

PMID- 12050082
TI  - Distinct origins of neocortical projection neurons and interneurons in vivo.
AB  - Recent studies in rodents have suggested that some cortical GABAergic
      interneurons arise within the neuroepithelium of the subcortical telencephalon
      then migrate dorsally into the cerebral cortex. These studies have relied heavily
      on short-term organotypic culture methods and on the analysis of mutant mice that
      die during the neonatal period. The purpose of this study is to ascertain
      directly whether cells labeled in the subcortical telencephalon in vivo
      differentiate into mature cortical interneurons and whether any cortical
      interneurons arise from the dorsal, cortical neuroepithelium. Mitotic cells
      within the neonatal cortex or subcortical telencephalon were labeled by focal
      injections of [(3)H]thymidine into the brains of neonatal ferrets. The fates of
      labeled cells were assessed in mature animals 6 weeks later. Our results suggest
      that many cortical interneurons, but not cortical projection neurons, derive from
      the subcortical telencephalon. Conversely, cortical projection neurons, but few
      if any interneurons, are generated within the proliferative zones of the
      neocortex.

PMID- 12050084
TI  - Unilateral lesions of the cholinergic basal forebrain and fornix in one
      hemisphere and inferior temporal cortex in the opposite hemisphere produce severe
      learning impairments in rhesus monkeys.
AB  - It has been proposed that isolation of the inferior temporal cortex and medial
      temporal lobe from their cholinergic afferents results in a severe anterograde
      amnesia. To test this hypothesis directly, seven rhesus monkeys received a
      unilateral immunotoxic lesion of the cholinergic cells of the basal forebrain
      with an ipsilesional section of the fornix. In a second surgery, inferior
      temporal cortex was ablated in the opposite hemisphere. All animals were severely
      impaired at learning visual scenes and object-reward associations. The impairment
      in learning scenes was correlated with cholinergic cell loss in the basal
      forebrain, but not with generalized tissue damage. Two monkeys served as surgical
      controls with saline injection in place of the immunotoxin, but all other
      procedures the same, and were not as severely impaired as those with immunotoxic
      lesions. Previous work has shown that monkeys with bilateral section of the
      anterior temporal stem (white matter of the temporal lobe), amygdala and fornix
      show a severe new learning impairment, and provide a model of human medial
      temporal lobe amnesia. One effect of this combined ablation is to isolate
      inferior temporal cortex and medial temporal lobe from their cholinergic
      afferents, possibly in addition to a direct disruption of the hippocampal system.
      The results of the present study, then, provide a novel link between the
      mechanisms of medial temporal lobe amnesia and Alzheimer's disease in which the
      cholinergic basal forebrain shows pathology. We propose that in both cases the
      mnemonic impairments result from isolating inferior temporal cortex and medial
      temporal lobe from their cholinergic afferents, possibly in addition to a direct
      disruption of the hippocampal system.

PMID- 12050085
TI  - Regional differences of the human sleep electroencephalogram in response to
      selective slow-wave sleep deprivation.
AB  - The purpose of this study was to assess the topographic changes in sleep
      recuperative processes in response to selective slow-wave sleep (SWS)
      deprivation. SWS was suppressed on two consecutive nights by means of acoustic
      stimulation. The electroencephalogram (EEG) power of baseline, deprivation and
      recovery nights was analysed in 1 Hz bins. During the SWS deprivation nights,
      large decreases of EEG power were found at frontopolar, central and parietal
      derivations encompassing the delta, theta and alpha range, while only slow delta
      (0.5-2 Hz) was affected at the frontal derivation. Recovery sleep was
      characterized by a generalized increase of power during non-REM sleep
      encompassing the delta, theta and alpha bands, with a clear antero-posterior
      gradient. The coherent behaviour of different EEG bands with traditionally
      different electrophysiological meanings during non-REM sleep suggests that, in
      light of the recent advances in sleep neurophysiology, a re-examination of the
      functional role of EEG rhythms during sleep is needed. The 'resistance' to
      selective SWS deprivation of the frontal area, together with its larger increase
      of EEG power during recovery, may be interpreted as a sign of a greater sleep
      need of the frontal cortical areas, confirming that some aspects of the
      regulatory processes of human sleep are local in nature and may show use
      dependent characteristics.

PMID- 12050083
TI  - Rapid distributed fronto-parieto-occipital processing stages during working
      memory in humans.
AB  - Cortical potentials were recorded from implanted electrodes during a difficult
      working memory task requiring rapid storage, modification and retrieval of
      multiple memoranda. Synchronous event-related potentials were generated in
      distributed occipital, parietal, Rolandic and prefrontal sites beginning
      approximately 130 ms after stimulus onset and continuing for >500 ms. Coherent
      phase-locked, event-related oscillations supported interaction between these
      dorsal stream structures throughout the task period. The Rolandic structures
      generated early as well as sustained potentials to sensory stimuli in the absence
      of movement. Activation peaks and phase lags between synaptic populations
      suggested that perceptual processing occurred exclusively in the visual
      association cortex from approximately 90 to 130 ms, with its results projected to
      fronto-parietal areas for interpretation from approximately 130 to 280 ms. The
      direction of interaction then appeared to reverse from approximately 300 to 400
      ms, consistent with mental arithmetic being performed by fronto-parietal areas
      operating upon a visual scratch pad in the dorsolateral occipital cortex. A
      second reversal, from approximately 420 to 600 ms, may have represented an
      updating of memoranda stored in fronto-parietal sites. Lateralized perisylvian
      oscillations suggested an articulatory loop. Anterior cingulate activity was
      evoked by feedback signals indicating errors. These results indicate how a fronto
      centro-parietal 'central executive' might interact with an occipital visual
      scratch pad, perisylvian articulatory loop and limbic monitor to implement the
      sequential stages of a complex mental operation.

PMID- 12050087
TI  - Effects of illumination intensity and direction on object coding in macaque
      inferior temporal cortex.
AB  - Single unit activity in area TE was recorded from two macaques as they viewed 3D
      appearing rendered objects that were illuminated from different directions
      (without cast shadows) and intensities of illumination. The average modulation
      produced by changes in illumination intensity or direction was rather moderate,
      with the majority of the neurons responding invariantly to these lighting
      variables. When neural activity was affected by illumination direction, it was
      not manifested as a preference for a particular direction of illumination by a
      given neuron. Instead, the tuning appeared to be to the relative brightness of a
      given shaped surface at a given orientation. The modulation to changes in
      illumination direction was considerably smaller than that produced by changes in
      object shape. Most of the neurons that were unaffected by changes in illumination
      direction responded much less to silhouettes of these objects, indicating that
      these neurons were also sensitive to an object's inner features. The neuronal
      invariance for shading variations may provide the basis for the invariance of
      object recognition under changes in illumination.

PMID- 12050088
TI  - Degenerative age changes in white matter connectivity visualized in vivo using
      magnetic resonance imaging.
AB  - Age effects on the signal characteristics of white matter (WM) were examined via
      magnetic resonance imaging (MRI). Global and local patterns of WM degeneration
      were demonstrated using a new image analysis methodology. Significant cross
      sectional and longitudinal age effects were found in the WM, primarily in the
      left hemisphere. Importantly, signal changes, which likely reflect WM
      demyelination, and changes in water, protein and mineral content of tissue, were
      unrelated to volumetric changes. Thus, measures of tissue characteristics provide
      unique and complementary information to widely used measures of brain atrophy.
      Moreover, signal measurements displayed stronger associations with age and can
      potentially be more sensitive than volumetric measures as indicators of
      preclinical disease, because they reflect changes in the underlying tissue
      composition. To our knowledge, our study is the first documentation of
      longitudinal age- and region-dependent changes in magnetic resonance signal
      characteristics of WM fibers, reflecting underlying degenerative effects of
      aging.

PMID- 12050086
TI  - The epigenesis of planum temporale asymmetry in twins.
AB  - Variation in hemispheric asymmetry of the planum temporale (PT) has been related
      to verbal ability. The degree to which genetic and environmental factors mediate
      PT asymmetry is not known. This study examined the heritability for planar
      asymmetry in 12 dizygotic (DZ) and 27 monozygotic (MZ) male twin pairs who were
      between 6 and 16 years of age. There was weak but positive evidence for
      heritability of planar asymmetry. Co-twin similarity for planar asymmetry and
      Sylvian fissure morphology increased when excluding twins discordant for writing
      hand and when excluding twins exhibiting birth weight differences >20% from the
      analyses. Birth weight differences were also related to twin differences in total
      cerebral volume, but not central sulcus asymmetry. These results suggest that
      exogenous perinatal factors affect the epigenesis of planar asymmetry
      development.

PMID- 12050089
TI  - The neural substrates of biological motion perception: an fMRI study.
AB  - We used fMRI to identify the brain areas related to the perception of biological
      motion (4 T EPI; whole brain). In experiment 1, 10 subjects viewed biological
      motion (a human figure jumping up and down, composed of 21 dots), alternating
      with a control stimulus created by applying autoregressive models to the
      biological motion stimulus (such that the dots' speeds and amplitudes were
      preserved whereas their linking structure was not). The lengths of the stimulus
      bouts varied, and therefore the transitions between biological motion and control
      stimuli were unpredictable. Subjects had to indicate with a button press when
      each transition occurred. In a related biological motion task, subjects detected
      short (1 s) disturbances within these displays. We also examined the neural
      substrates of motion and shape perception, as well as motor imagery, to determine
      whether or not the cortical regions involved in these processes are also
      recruited during biological motion perception. Subjects viewed linear motion
      displays alternating with static dots and a series of common objects alternating
      with band-limited white noise patterns. Subjects also generated imagery of their
      own arm movements alternating with visual imagery of common objects. Biological
      motion specific BOLD signal was found within regions of the lingual gyrus at the
      cuneus border, showing little overlap with object recognition, linear motion or
      motion imagery areas. The lingual gyrus activation was replicated in a second
      experiment that also mapped retinotopic visual areas in three subjects. The
      results suggest that a region of the lingual gyrus within VP is involved in
      higher-order processing of motion information.

PMID- 12050090
TI  - Point: population stratification: a problem for case-control studies of candidate
      gene associations?

PMID- 12050091
TI  - Counterpoint: bias from population stratification is not a major threat to the
      validity of conclusions from epidemiological studies of common polymorphisms and
      cancer.

PMID- 12050092
TI  - Incorporating genetic susceptibility feedback into a smoking cessation program
      for African-American smokers with low income.
AB  - PURPOSE: Markers of genetic susceptibility to tobacco-related cancers could
      personalize harms of smoking and motivate cessation. Our objective was to assess
      whether a multicomponent intervention that included feedback about genetic
      susceptibility to lung cancer increased risk perceptions and rates of smoking
      cessation compared with a standard cessation intervention. EXPERIMENTAL DESIGN:
      Our design was a two-arm trial with eligible smokers randomized in a 1:2 ratio to
      Enhanced Usual Care or Biomarker Feedback (BF). Surveys were conducted at
      baseline, 6, and 12 months later. The setting was an inner city community health
      clinic. African-American patients who were current smokers (n = 557) were
      identified by chart abstraction and provider referral. All smokers received a
      self-help manual and, if appropriate, nicotine patches. Smokers in the BF arm
      also were offered a blood test for genotyping the GST(3) gene (GSTM1), sent a
      test result booklet, and called up to four times by a health educator. Prevalent
      abstinence was assessed by self-report of having smoked no cigarettes in the
      prior 7 days at the 6- and 12-month follow-ups and sustained abstinence, i.e.,
      not smoking at either follow-up or in-between. RESULTS: Smoking cessation was
      greater for the BF arm than the Enhanced Usual Care arm (19% versus 10%,
      respectively; P < 0.006) at 6 months but not at 12 months. CONCLUSIONS: Smokers
      agreed to genetic feedback as part of a multicomponent cessation program.
      Although the program increased short-term cessation rates compared with standard
      intervention, genetic feedback of susceptibility may not benefit smokers with
      high baseline risk perceptions.

PMID- 12050093
TI  - Perceived barriers and benefits to colon cancer screening among African Americans
      in North Carolina: how does perception relate to screening behavior?
AB  - This study investigated perceived barriers and benefits, as conceptualized by the
      Health Belief Model,in relation to screening for colorectal cancer (CRC) among
      African-American adults participating in a church-based health promotion program.
      CRC is one of the most common cancers and is the second leading cause of cancer
      death for men and women. Screening can be effective at detecting cancer at
      treatable stages, but a large proportion of people at risk have not been screened
      or are not screened regularly, as recommended by national guidelines. In this
      study, logistic regression was used to assess the relation of barriers and
      benefits to self-reported history of fecal occult blood testing (FOBT), flexible
      sigmoidoscopy, and colonoscopy. Barriers were significantly negatively related to
      recent FOBT and recent sigmoidoscopy. Benefits were significantly related to
      having a recent sigmoidoscopy and a recent colonoscopy but not to recent FOBT.
      Results suggest that the way people perceive sigmoidoscopy and colonoscopy may
      differ from FOBT with respect to the relative importance of perceived benefits
      versus barriers. Findings are discussed within the context of these Health Belief
      Model constructs and implications for health promotion programming.

PMID- 12050094
TI  - Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+ mouse, a
      model of familial adenomatous polyposis.
AB  - Curcumin, the major yellow pigment in turmeric, prevents the development of
      adenomas in the intestinal tract of the C57Bl/6J Min/+ mouse, a model of human
      familial APC. To aid the rational development of curcumin as a colorectal cancer
      preventive agent, we explored the link between its chemopreventive potency in the
      Min/+ mouse and levels of drug and metabolites in target tissue and plasma. Mice
      received dietary curcumin for 15 weeks, after which adenomas were enumerated.
      Levels of curcumin and metabolites were determined by high-performance liquid
      chromatography in plasma, tissues, and feces of mice after either long-term
      ingestion of dietary curcumin or a single dose of [(14)C]curcumin (100 mg/kg) via
      the i.p. route. Whereas curcumin at 0.1% in the diet was without effect, at 0.2
      and 0.5%, it reduced adenoma multiplicity by 39 and 40%, respectively, compared
      with untreated mice. Hematocrit values in untreated Min/+ mice were drastically
      reduced compared with those in wild-type C57Bl/6J mice. Dietary curcumin
      partially restored the suppressed hematocrit. Traces of curcumin were detected in
      the plasma. Its concentration in the small intestinal mucosa, between 39 and 240
      nmol/g of tissue, reflects differences in dietary concentration. [(14)C]Curcumin
      disappeared rapidly from tissues and plasma within 2-8 h after dosing. Curcumin
      may be useful in the chemoprevention of human intestinal malignancies related to
      Apc mutations. The comparison of dose, resulting curcumin levels in the
      intestinal tract, and chemopreventive potency suggests tentatively that a daily
      dose of 1.6 g of curcumin is required for efficacy in humans. A clear advantage
      of curcumin over nonsteroidal anti-inflammatory drugs is its ability to decrease
      intestinal bleeding linked to adenoma maturation.

PMID- 12050095
TI  - Diet activity, and lifestyle associations with p53 mutations in colon tumors.
AB  - Inactivation of the p53 tumor suppressor gene is a common event in the
      development of colon cancer. We use data collected as part of a multicenter case
      control study of colon cancer to evaluate associations between p53 mutations and
      diet and lifestyle factors. p53 mutational status was determined for 1458
      incident cases of colon cancer using single-strand conformational
      polymorphism/sequencing of exons 5-8. We determined associations among those with
      and without mutations compared with population-based controls (N = 2410) and to
      cases with p53 mutations compared with cases without p53 mutations. Associations
      also were examined by location and function of specific types of p53 mutations.
      p53 mutations were identified in tumors in 47.1% of cases; 81.9% of people with
      mutations had a missense mutation. Cases with a p53 mutation were more likely to
      consume a Western-style diet, compared with controls [odds ratio (OR), 2.03; 95%
      confidence interval (CI), 1.53-2.69], than were cases who were p53 wild type
      (Wt), compared with controls (OR, 1.57;95% CI, 1.20-2.06). Specific components of
      the Western-style diet, including diets with a high glycemic load (mutation
      versus control: OR, 1.48; 95% CI, 1.11-1.98 and Wt versus control: OR, 0.98; 95%
      CI, 0.75-1.28) and diets high in red meat, fast food, and trans-fatty acid
      (mutation versus control: OR, 1.92; 95% CI, 1.47-2.50 and Wt versus control: OR,
      1.39; 95% CI, 1.08-1.80) appeared to be most strongly associated with p53
      mutations. Diets with a high glycemic load (relative to lowest intake) were
      significantly associated with missense mutations (OR, 1.69; 95% CI, 1.23-2.33
      comparing p53+ to controls and OR, 1.72; 95% CI, 1.19-2.50 comparing cases p53+
      to cases p53 Wt), as were diets high in red meat, fast food, and trans-fatty
      acids (OR, 1.92; 95% CI, 1.14-2.56 comparing p53+ to controls and OR, 1.40; 95%
      CI, 1.00-1.98 comparing cases p53+ to cases p53 Wt). Physical inactivity, large
      body mass index, cigarette smoking, using aspirin/nonsteroidal anti-inflammatory
      drugs, and other dietary factors appeared to be comparably associated with colon
      cancer in those with and without p53 mutations. These data suggest that
      components of a Western-style diet such as high consumption of red meat and foods
      that increase glycemic load are associated with a p53 disease pathway.

PMID- 12050096
TI  - Androgenetic alopecia and prostate cancer: findings from an Australian case
      control study.
AB  - The purpose of this study was to examine the relationship between androgenetic
      alopecia (AA) and prostate cancer with particular emphasis on early age at
      diagnosis and higher grade tumors. We conducted an age-stratified, population
      based case-control study in Australia of men who were diagnosed before 70 years
      of age during 1994-1997 with histopathology-confirmed adenocarcinoma of the
      prostate, excluding well-differentiated tumors. Controls were selected from the
      electoral rolls, and the frequency was matched on age. After excluding subjects
      with missing values, the analysis was based on 1446 cases and 1390 controls of
      whom direct observations were made of their pattern of AA during face-to-face
      interviews. Our data suggest an association between prostate cancer and vertex
      baldness; compared with men who had no balding, the adjusted odds ratio (OR) was
      1.54 (1.19-2.00). No associations were found between prostate cancer and frontal
      baldness or when frontal baldness was present concurrently with vertex baldness.
      The ORs were 0.98 (0.79-1.23) and 1.14 (0.90-1.45), respectively. The highest ORs
      were for high-grade disease in men 60-69 years of age: 1.80 (1.02-3.16) for
      frontal baldness; 2.91 (1.59-5.32) for vertex baldness; and 1.95 (1.10-3.45) for
      frontal and vertex baldness. This association between the pattern of AA and
      prostate cancer points to shared androgen pathways that are worthy of additional
      investigation.

PMID- 12050097
TI  - The G gamma / T-15 transgenic mouse model of androgen-independent prostate
      cancer: target cells of carcinogenesis and the effect of the vitamin D analogue
      EB 1089.
AB  - Transgenic mouse models of prostate cancer provide unique opportunities to
      understand the molecular events in prostate carcinogenesis and for the
      preclinical testing of new therapies. We studied the G gamma T-15 transgenic
      mouse line, which contains the human fetal globin promoter linked to SV40 T
      antigen (Tag) and which develops androgen-independent prostate cancer. Using the
      immunohistochemistry of normal mouse prostates before tumor formation, we showed
      that the target cells of carcinogenesis in G gamma T-15 mice are located in the
      basal epithelial layer. We tested the efficacy of the 1,25(OH)(2)D(3) analogue,
      EB 1089, to chemoprevent prostate cancer in these transgenic mice. Compared with
      treatment with placebo, treatment with EB 1089 at three different time points
      before the onset of prostate tumors in mice did not prevent or delay tumor onset.
      However, EB 1089 significantly inhibited prostate tumor growth. At the highest
      dose, EB 1089 inhibited prostate tumor growth by 60% (P = 0.0003) and the growth
      in the number of metastases, although this dose also caused significant
      hypercalcemia and weight loss. We conducted several in vitro experiments to
      explore why EB 1089 did not prevent the occurrence of the primary tumors. EB 1089
      significantly inhibited the growth of a Tag-expressing human prostate epithelial
      cell line, BPH-1, and an androgen-insensitive subline of LNCaP cells [which was
      not inhibited by 1,25(OH)(2)D(3)]. Thus, neither Tag expression nor androgen
      insensitivity explain the absence of chemopreventive effect. Conversely, neither
      1,25(OH)(2)D(3) nor EB 1089 inhibited the growth of the normal rat prostate basal
      epithelial cell line NRP-152. It is likely that EB 1089 was not effective in
      delaying the growth of the primary tumor in G gamma T-15 transgenic mice because
      the target cells of carcinogenesis in these mice are located in the basal
      epithelial layer. We conclude that G gamma T-15 transgenic mice are a useful
      model for testing vitamin D-based therapies in androgen-insensitive prostate
      cancer but are not suitable for studies of vitamin D-based chemoprevention. The
      superiority of EB 1089 over 1,25(OH)(2)D(3) in the growth suppression of androgen
      insensitive prostate cancer cells supports the use of EB 1089 in androgen
      insensitive prostate cancer.

PMID- 12050098
TI  - Risk of subsequent breast cancer in relation to characteristics of screening
      mammograms from women less than 50 years of age.
AB  - This investigation was conducted to assess the predictive value of calcifications
      and densities in mammograms from women <50 years of age for subsequent diagnosis
      of breast cancer. In a population-based study, prior screening mammograms taken
      before age 50 in 547 women with breast cancer and 472 controls were reviewed by a
      single radiologist. The relative risk (RR) of subsequent breast cancer increased
      with the percentage of the area of the mammogram that was mammographically dense
      [RR in succeeding quartiles of density = 1.0, 1.7 (1.1-2.6), 3.3 (2.2-5.0), and
      4.0 (2.7-6.0)]; in relation to Wolfe parenchymal pattern class P2 [RR = 3.1 (2.2
      4.3)] or DY [RR = 5.6 (3.2-10.0)]; and in relation to calcifications of class 1
      (pleomorphic of any distribution) or class 2 (various morphological types that
      are regional, grouped, clustered, segmental, or linear in distribution) [RR = 3.0
      (1.4-7.1), and 1.8 (1.2-2.6), respectively]. Women with radiographically dense
      mammograms and class 1 or 2 calcifications were at >10- and approximately 6-fold
      greater risk, respectively, than women with breasts of low density and no
      calcifications. Densities and parenchymal patterns were most strongly associated
      with breast cancer being diagnosed in the next 3 years. Class 1 and 2
      calcifications were most strongly predictive of an increased risk in 3-6 years.
      Class 1 calcifications were strongly predictive of the breast in which the
      subsequent cancer occurred. Women <50 years of age with class 1 or 2
      calcifications or mammographically dense breasts, or both, should receive high
      priority for further evaluation and regular breast cancer screening.

PMID- 12050099
TI  - Effects of perillyl alcohol on melanoma in the TPras mouse model.
AB  - This study evaluates the chemopreventive effects of topically applied perillyl
      alcohol on the development of melanoma in TPras transgenic mice. Our strategy was
      to target critical pathways in the development of melanoma, in particular, the
      ras pathway. Ras has been shown in our experimental mouse model, as well as
      others, to be important in the development and maintenance of melanomas. Perillyl
      alcohol (POH), a naturally occurring monoterpene, inhibits the isoprenylation of
      small G protein, including Ras. POH (10 mM) was applied to the shaved dorsal skin
      of TPras mice starting 1 week before five treatments of dimethylbenz[a]anthracene
      (50 microg) and was continued for 38 weeks. We observed a delay in the appearance
      of tumors and a 25-35% reduction in melanoma incidence. POH treatment of melanoma
      cells in vitro reduced the levels of detectable Ras protein and inhibits the
      activation of downstream targets, mitogen-activated protein kinases and Akt. POH
      only minimally induced apoptosis in this system. Pretreatment but not post
      treatment of the melanoma cells with POH, however, markedly reduced levels of UV
      induced reactive oxygen species. These studies suggest that POH inhibition of the
      Ras signaling pathway may be an effective target for chemoprevention of melanoma.

PMID- 12050100
TI  - Lack of association between adipose tissue distribution and IGF-1 and IGFBP-3 in
      men and women.
AB  - Insulin, insulin-like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3),
      and obesity, and in particular visceral obesity, are putative cancer risk
      factors. Little is known, however, about the relationship between IGFs and
      obesity. We investigated the relationship between adipose tissue distribution and
      IGF-1 and IGFBP-3. Single-slice abdominal computed tomography scanning through
      the L4-L5 interspace was used to measure visceral adipose tissue (VAT) and
      subcutaneous adipose tissue (SQAT) in 432 community-based subjects (267 men, 165
      women; ages, 55-77), participating in a cancer screening trial. Insulin, IGF-1,
      IGFBP-3, and the ratio of IGF-1:IGFBP-3, measured by radioimmunoassay, were
      compared with age, body mass index, absolute and relative VAT and SQAT, and total
      abdominal fat. We found that men had a higher mean IGF-1 (129.5 versus 108.9
      ng/ml; P < 0.0001) and more VAT (201.5 cm(3) versus 166.6 cm(3); P < 0.0001) than
      women. In men and women, there was no correlation between IGF-1, IGFBP-3, or the
      ratio of IGF-1:IGFBP-3 with body mass index, total fat, VAT or SQAT, or fasting
      insulin. In contrast, fasting insulin was highly correlated to all measures of
      obesity (P = 0.0001). We conclude that obesity, adipose tissue distribution, and
      in particular VAT are not correlated with IGF-1, IGFBP-3, or the molar ratio of
      IGF-1:IGFBP-3. The lack of association between obesity and the IGF-1 axis
      suggests that the IGF-1 axis is not a likely mediator between VAT and disease.

PMID- 12050101
TI  - Her-2/neu gene amplification in ductal carcinoma in situ of the breast.
AB  - This study evaluated the relative frequencies of HER-2/neu gene amplification in
      ductal carcinoma in situ (DCIS)-associated invasive breast cancer and DCIS alone.
      We examined archival tissue samples of 100 DCIS lesions with an invasive
      component (cases) and 100 without an invasive component (controls), with cases
      and controls matched by pathologic nuclear grade. HER-2/neu gene amplification
      was determined by fluorescence in situ hybridization. We compared HER-2/neu gene
      amplification in DCIS lesions only, irrespective of the presence or absence of an
      invasive component. HER-2/neu gene amplification occurred significantly less
      frequently in the cases (26%) than in the controls (40%), with an odds ratio of
      0.35 (95% confidence interval, 0.17-0.72; P < 0.004) after adjustment for
      pathologic and quantitative-image-analyzed morphometric nuclear grade. The HER
      2/neu gene also was amplified more frequently in higher- than in lower-grade DCIS
      alone (56% versus 19%, respectively; P < 0.0001) or in higher- than in lower
      grade DCIS with invasive cancer (44% versus 2%, respectively; P < 0.00001).
      Future studies should examine the potential roles of HER-2/neu and other
      biomarkers (e.g., p21 and Rb) as markers of the risk of DCIS patients for
      invasive breast cancer and as molecular targets of chemoprevention in breast
      intraepithelial neoplasia.

PMID- 12050110
TI  - Transmission of proteotoxicity across cellular compartments.

PMID- 12050111
TI  - When cell biology meets development: endocytic regulation of signaling pathways.

PMID- 12050112
TI  - Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound
      conformation.
AB  - Activation of gene transcription in mammalian cells requires several classes of
      coactivators that participate in different steps of the activation cascade. Using
      conventional and affinity chromatography, we have isolated a human coactivator
      complex that interacts directly with the C-terminal domain (CTD) of RNA
      polymerase II (Pol II). The CTD-binding complex is structurally and functionally
      indistinguishable from our previously isolated CRSP coactivator complex. The
      closely related, but transcriptionally inactive, ARC-L complex failed to interact
      with the CTD, indicating a significant biochemical difference between CRSP and
      ARC-L that may, in part, explain their functional divergence. Electron microscopy
      and three-dimensional single-particle reconstruction reveals a conformation for
      CTD-CRSP that is structurally distinct from unliganded CRSP or CRSP bound to
      SREBP-1a, but highly similar to CRSP bound to the VP16 activator. Together, our
      findings suggest that the human CRSP coactivator functions, at least in part, by
      mediating activator-dependent recruitment of RNA Pol II via the CTD.

PMID- 12050113
TI  - ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death
      triggered by expanded polyglutamine repeats.
AB  - Expansion of CAG trinucleotide repeats that encode polyglutamine is the
      underlying cause of at least nine inherited human neurodegenerative disorders,
      including Huntington's disease and spinocerebellar ataxias. PolyQ fragments
      accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce
      neuronal cell death. However, the molecular mechanism of polyQ-induced cell death
      is controversial. Here, we show the following: (1) polyQ with pathogenic repeat
      length triggers ER stress through proteasomal dysfunction; (2) ER stress
      activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/
      ) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress
      induced JNK activation and cell death. These findings suggest that ASK1 is a key
      element in ER stress-induced cell death that plays an important role in the
      neuropathological alterations in polyQ diseases.

PMID- 12050114
TI  - Phosphorylation of three regulatory serines of Tob by Erk1 and Erk2 is required
      for Ras-mediated cell proliferation and transformation.
AB  - tob is a member of an emerging family of genes with antiproliferative function.
      Tob is rapidly phosphorylated at Ser 152, Ser 154, and Ser 164 by Erk1 and Erk2
      upon growth-factor stimulation. Oncogenic Ras-induced transformation and growth
      factor-induced cell proliferation are efficiently suppressed by mutant Tob that
      carries alanines but not glutamates, mimicking phosphoserines, at these sites.
      Wild-type Tob inhibits cell growth when the three serine residues are not
      phosphorylated but is less inhibitory when the serines are phosphorylated.
      Because growth of Rb-deficient cells was not affected by Tob, Tob appears to
      function upstream of Rb. Intriguingly, cyclin D1 expression is elevated in serum
      starved tob(-/-) cells. Reintroduction of wild-type Tob and mutant Tob with
      serine-to-alanine but not to glutamate mutations on the Erk phosphorylation sites
      in these cells restores the suppression of cyclin D1 expression. Finally, the S
      phase population was significantly increased in serum-starved tob(-/-) cells as
      compared with that in wild-type cells. Thus, Tob inhibits cell growth by
      suppressing cyclin D1 expression, which is canceled by Erk1- and Erk2-mediated
      Tob phosphorylation. We propose that Tob is critically involved in the control of
      early G(1) progression.

PMID- 12050115
TI  - Phosphorylation of the mitotic regulator Pds1/securin by Cdc28 is required for
      efficient nuclear localization of Esp1/separase.
AB  - Sister chromatid separation at the metaphase-to-anaphase transition is induced by
      the proteolytic cleavage of one of the cohesin complex subunits. This process is
      mediated by a conserved protease called separase. Separase is associated with its
      inhibitor, securin, until the time of anaphase initiation, when securin is
      degraded in an anaphase-promoting complex/cyclosome (APC/C)-dependent manner. In
      budding yeast securin/Pds1 not only inhibits separase/Esp1, but also promotes its
      nuclear localization. The molecular mechanism and regulation of this nuclear
      targeting are presently unknown. Here we show that Pds1 is a substrate of the
      cyclin-dependent kinase Cdc28. Phosphorylation of Pds1 by Cdc28 is important for
      efficient binding of Pds1 to Esp1 and for promoting the nuclear localization of
      Esp1. Our results uncover a previously unknown mechanism for regulating the Pds1
      Esp1 interaction and shed light on a novel role for Cdc28 in promoting the
      metaphase-to-anaphase transition in budding yeast.

PMID- 12050116
TI  - Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork
      progression through telomeric and subtelomeric DNA.
AB  - In wild-type Saccharomyces cerevisiae, replication forks slowed during their
      passage through telomeric C(1-3)A/TG(1-3) tracts. This slowing was greatly
      exacerbated in the absence of RRM3, shown here to encode a 5' to 3' DNA helicase.
      Rrm3p-dependent fork progression was seen at a modified Chromosome VII-L
      telomere, at the natural X-bearing Chromosome III-L telomere, and at Y'-bearing
      telomeres. Loss of Rrm3p also resulted in replication fork pausing at specific
      sites in subtelomeric DNA, such as at inactive replication origins, and at
      internal tracts of C(1-3)A/TG(1-3) DNA. The ATPase/helicase activity of Rrm3p was
      required for its role in telomeric and subtelomeric DNA replication. Because
      Rrm3p was telomere-associated in vivo, it likely has a direct role in telomere
      replication.

PMID- 12050117
TI  - Mastermind mediates chromatin-specific transcription and turnover of the Notch
      enhancer complex.
AB  - Signaling through the Notch pathway activates the proteolytic release of the
      Notch intracellular domain (ICD), a dedicated transcriptional coactivator of CSL
      enhancer-binding proteins. Here we show that chromatin-dependent transactivation
      by the recombinant Notch ICD-CBF1 enhancer complex in vitro requires an
      additional coactivator, Mastermind (MAM). MAM provides two activation domains
      necessary for Notch signaling in mammalian cells and in Xenopus embryos. We show
      that the central MAM activation domain (TAD1) recruits CBP/p300 to promote
      nucleosome acetylation at Notch enhancers and activate transcription in vitro. We
      also find that MAM expression induces phosphorylation and relocalization of
      endogenous CBP/p300 proteins to nuclear foci in vivo. Moreover, we show that
      coexpression with MAM and CBF1 strongly enhances phosphorylation and proteolytic
      turnover of the Notch ICD in vivo. Enhanced phosphorylation of the ICD and p300
      requires a glutamine-rich region of MAM (TAD2) that is essential for Notch
      transcription in vivo. Thus MAM may function as a timer to couple transcription
      activation with disassembly of the Notch enhancer complex on chromatin.

PMID- 12050118
TI  - Keratin 17 null mice exhibit age- and strain-dependent alopecia.
AB  - Onset of type I keratin 17 (K17) synthesis marks the adoption of an appendageal
      fate within embryonic ectoderm, and its expression persists in specific cell
      types within mature hair, glands, and nail. We report that K17 null mice develop
      severe alopecia during the first week postbirth, correlating with hair fragility,
      alterations in follicular histology, and apoptosis in matrix cells. These
      alterations are incompletely penetrant and normalize starting with the first
      postnatal cycle. Absence of a hair phenotype correlates with a genetic strain
      dependent compensation by related keratins, including K16. These findings reveal
      a crucial role for K17 in the structural integrity of the first hair produced and
      the survival of hair-producing cells. Given that identical inherited mutations in
      this gene can cause either pachyonychia congenita or steatocystoma multiplex, the
      features of this mouse model suggest that this clinical heterogeneity arises from
      a cell type-specific, genetically determined compensation by related keratins.

PMID- 12050119
TI  - Hox11 paralogous genes are essential for metanephric kidney induction.
AB  - The mammalian Hox complex is divided into four linkage groups containing 13 sets
      of paralogous genes. These paralogous genes have retained functional redundancy
      during evolution. For this reason, loss of only one or two Hox genes within a
      paralogous group often results in incompletely penetrant phenotypes which are
      difficult to interpret by molecular analysis. For example, mice individually
      mutant for Hoxa11 or Hoxd11 show no discernible kidney abnormalities.
      Hoxa11/Hoxd11 double mutants, however, demonstrate hypoplasia of the kidneys. As
      described in this study, removal of the last Hox11 paralogous member, Hoxc11,
      results in the complete loss of metanephric kidney induction. In these triple
      mutants, the metanephric blastema condenses, and expression of early patterning
      genes, Pax2 and Wt1, is unperturbed. Eya1 expression is also intact. Six2
      expression, however, is absent, as is expression of the inducing growth factor,
      Gdnf. In the absence of Gdnf, ureteric bud formation is not initiated. Molecular
      analysis of this phenotype demonstrates that Hox11 control of early metanephric
      induction is accomplished by the interaction of Hox11 genes with the pax-eya-six
      regulatory cascade, a pathway that may be used by Hox genes more generally for
      the induction of multiple structures along the anteroposterior axis.

PMID- 12050121
TI  - Sex steroids and the construction and conservation of the adult skeleton.
AB  - Here we review and extend a new unitary model for the pathophysiology of
      involutional osteoporosis that identifies estrogen (E) as the key hormone for
      maintaining bone mass and E deficiency as the major cause of age-related bone
      loss in both sexes. Also, both E and testosterone (T) are key regulators of
      skeletal growth and maturation, and E, together with GH and IGF-I, initiate a 3-
      to 4-yr pubertal growth spurt that doubles skeletal mass. Although E is required
      for the attainment of maximal peak bone mass in both sexes, the additional action
      of T on stimulating periosteal apposition accounts for the larger size and
      thicker cortices of the adult male skeleton. Aging women undergo two phases of
      bone loss, whereas aging men undergo only one. In women, the menopause initiates
      an accelerated phase of predominantly cancellous bone loss that declines rapidly
      over 4-8 yr to become asymptotic with a subsequent slow phase that continues
      indefinitely. The accelerated phase results from the loss of the direct
      restraining effects of E on bone turnover, an action mediated by E receptors in
      both osteoblasts and osteoclasts. In the ensuing slow phase, the rate of
      cancellous bone loss is reduced, but the rate of cortical bone loss is unchanged
      or increased. This phase is mediated largely by secondary hyperparathyroidism
      that results from the loss of E actions on extraskeletal calcium metabolism. The
      resultant external calcium losses increase the level of dietary calcium intake
      that is required to maintain bone balance. Impaired osteoblast function due to E
      deficiency, aging, or both also contributes to the slow phase of bone loss.
      Although both serum bioavailable (Bio) E and Bio T decline in aging men, Bio E is
      the major predictor of their bone loss. Thus, both sex steroids are important for
      developing peak bone mass, but E deficiency is the major determinant of age
      related bone loss in both sexes.

PMID- 12050120
TI  - Desert Hedgehog/Patched 1 signaling specifies fetal Leydig cell fate in testis
      organogenesis.
AB  - Establishment of the steroid-producing Leydig cell lineage is an event downstream
      of Sry that is critical for masculinization of mammalian embryos. Neither the
      origin of fetal Leydig cell precursors nor the signaling pathway that specifies
      the Leydig cell lineage is known. Based on the sex-specific expression patterns
      of Desert Hedgehog (Dhh) and its receptor Patched 1 (Ptch1) in XY gonads, we
      investigated the potential role of DHH/PTCH1 signaling in the origin and
      specification of fetal Leydig cells. Analysis of Dhh(-/-) XY gonads revealed that
      differentiation of fetal Leydig cells was severely defective. Defects in Leydig
      cell differentiation in Dhh(-/-) XY gonads did not result from failure of cell
      migration from the mesonephros, thought to be a possible source of Leydig cell
      precursors. Nor did DHH/PTCH1 signaling appear to be involved in the
      proliferation or survival of fetal Leydig precursors in the interstitium of the
      XY gonad. Instead, our results suggest that DHH/PTCH1 signaling triggers Leydig
      cell differentiation by up-regulating Steroidogenic Factor 1 and P450 Side Chain
      Cleavage enzyme expression in Ptch1-expressing precursor cells located outside
      testis cords.

PMID- 12050122
TI  - Genetics of osteoporosis.
AB  - Osteoporosis is a common multifactorial disorder of reduced bone mass. The
      disorder in its most common form is generalized, affecting the elderly, both
      sexes, and all racial groups. Multiple environmental factors are involved in the
      pathogenesis. Genes also play a major role as reflected by heritability of many
      components of bone strength. Quantitative phenotypes in bone strength in the
      normal population do not conform to a monogenetic mode of inheritance. The common
      form of osteoporosis is generally considered to be a polygenic disorder arising
      from the interaction of common polymorphic alleles at quantitative trait loci,
      with multiple environmental factors. Finding the susceptibility genes underlying
      osteoporosis requires identifying specific alleles that coinherit with key
      heritable phenotypes in bone strength. Because of the close correspondence among
      mammalian genomes, identification of the genes underlying bone strength in
      mammals such as the mouse is likely to be of major assistance in human studies.
      Identification of susceptibility genes for osteoporosis is one of several
      important approaches toward the long-term goal of understanding the molecular
      biology of the normal variation in bone strength and how it may be modified to
      prevent osteoporosis. As with all genetic studies in humans, these scientific
      advances will need to be made in an environment of legal and ethical safeguards
      that are acceptable to the general public.

PMID- 12050124
TI  - The impact of genomics and proteomics on endocrinology.

PMID- 12050123
TI  - Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes:
      autoantibodies, autoantigens, and their applicability in diagnosis and disease
      prediction.
AB  - Recent progress in the understanding of autoimmune adrenal disease, including a
      detailed analysis of a group of patients with Addison's disease (AD), has been
      reviewed. Criteria for defining an autoimmune disease and the main features of
      autoimmune AD (history, prevalence, etiology, histopathology, clinical and
      laboratory findings, cell-mediated andhumoral immunity, autoantigens and their
      autoepitopes, genetics, animal models, associated autoimmune diseases,
      pathogenesis, natural history, therapy) have been described. Furthermore, the
      autoimmune polyglandular syndromes (APS) associated with AD (revised
      classification, animal models, genetics, natural history) have been discussed. Of
      Italian patients with primary AD (n = 317), 83% had autoimmune AD. At the onset,
      all patients with autoimmune AD (100%) had detectable adrenal cortex and/or
      steroid 21-hydroxylase autoantibodies. In the course of natural history of
      autoimmune AD, the presence of adrenal cortex and/or steroid 21-hydroxylase
      autoantibodies identified patients at risk to develop AD. Different risks of
      progression to clinical AD were found in children and adults, and three stages of
      subclinical hypoadrenalism have been defined. Normal or atrophic adrenal glands
      have been demonstrated by imaging in patients with clinical or subclinical AD.
      Autoimmune AD presented in four forms: as APS type 1 (13% of the patients), APS
      type 2 (41%), APS type 4 (5%), and isolated AD (41%). There were differences in
      genetics, age at onset, prevalence of adrenal cortex/21-hydroxylase
      autoantibodies, and associated autoimmune diseases in these groups. "Incomplete"
      forms of APS have been identified demonstrating that APS are more prevalent than
      previously reported. A varied prevalence of hypergonadotropic hypogonadism in
      patients with AD and value of steroid-producing cells autoantibodies reactive
      with steroid 17alpha-hydroxylase or P450 side-chain cleavage enzyme as markers of
      this disease has been discussed. In addition, the prevalence, characteristic
      autoantigens, and autoantibodies of minor autoimmune diseases associated with AD
      have been described. Imaging of adrenal glands, genetic tests, and biochemical
      analysis have been shown to contribute to early and correct diagnosis of primary
      non-autoimmune AD in the cases of hypoadrenalism with undetectable adrenal
      autoantibodies. An original flow chart for the diagnosis of AD has been proposed.

PMID- 12050125
TI  - Hormonal genomics.
AB  - The availability of the human genomic sequence is changing the way in which
      biological questions are addressed. Based on the prediction of genes from
      nucleotide sequences, homologies among their encoded amino acids can be analyzed
      and used to place them in distinct families. This serves as a first step in
      building hypotheses for testing the structural and functional properties of
      previously uncharacterized paralogous genes. As genomic information from more
      organisms becomes available, these hypotheses can be refined through comparative
      genomics and phylogenetic studies. Instead of the traditional single-gene
      approach in endocrine research, we are beginning to gain an understanding of
      entire mammalian genomes, thus providing the basis to reveal subfamilies and
      pathways for genes involved in ligand signaling. The present review provides
      selective examples of postgenomic approaches in the analysis of novel genes
      involved in hormonal signaling and their chromosomal locations, polymorphisms,
      splicing variants, differential expression, and physiological function. In the
      postgenomic era, scientists will be able to move from a gene-by-gene approach to
      a reconstructionistic one by reading the encyclopedia of life from a global
      perspective. Eventually, a community-based approach will yield new insights into
      the complexity of intercellular communications, thereby offering us an
      understanding of hormonal physiology and pathophysiology.

PMID- 12050127
TI  - Genetic approaches to unraveling reproductive disorders: examples of bedside to
      bench research in the genomic era.
AB  - Despite the rapid advances in medical genetics, many clinicians and investigators
      remain unaware of the general approaches that can be used to map genes. Although
      there are specific challenges to using genetic approaches in reproductive
      medicine, the following report summarizes mapping efforts for three diseases:
      adrenal hypoplasia congenita, hypergonadotropic ovarian failure, and polycystic
      ovary syndrome. The themes of rare and novel phenotypes, genetically homogenous
      populations, and genotype/phenotype correlations are emphasized.

PMID- 12050128
TI  - Microarray-based expression profiling of normal and malignant immune cells.
AB  - Recent advances in gene microarray technology have facilitated global analyses of
      gene expression profiles in normal and malignant immune cells. Great strides have
      been made in our understanding of molecular differences among various types of
      immune cells, the process of T and B cell activation, and the genomic changes
      that convert normal cells to malignant ones. Genomic analysis has become a
      crucial aspect of cancer classification, diagnosis, therapy, and prognosis. This
      technology has the potential to reveal the comprehensive transcriptional
      alterations that dictate fundamental biological processes such as signal
      transduction in response to specific stimuli, cell growth, differentiation, and
      apoptosis. While reaping the benefits of genomic analyses, it is important to
      realize its limitations with respect to accuracy of interpretation,
      reproducibility, and signal detection. It is crucial to optimize signals for
      individual probe-target pairs and to develop a uniform set of criteria for data
      analyses. The development of a public-access database of results from individual
      laboratories will pave the way for identifying discrepancies and advancing
      scientific breakthroughs.

PMID- 12050129
TI  - In ovo transplantation of enteric nervous system precursors from vagal to sacral
      neural crest results in extensive hindgut colonisation.
AB  - The enteric nervous system (ENS) is derived from vagal and sacral neural crest
      cells (NCC). Within the embryonic avian gut, vagal NCC migrate in a rostrocaudal
      direction to form the majority of neurons and glia along the entire length of the
      gastrointestinal tract, whereas sacral NCC migrate in an opposing caudorostral
      direction, initially forming the nerve of Remak, and contribute a smaller number
      of ENS cells primarily to the distal hindgut. In this study, we have investigated
      the ability of vagal NCC, transplanted to the sacral region of the neuraxis, to
      colonise the chick hindgut and form the ENS in an experimentally generated
      hypoganglionic hindgut in ovo model. Results showed that when the vagal NC was
      transplanted into the sacral region of the neuraxis, vagal-derived ENS precursors
      immediately migrated away from the neural tube along characteristic pathways,
      with numerous cells colonising the gut mesenchyme by embryonic day (E) 4. By E7,
      the colorectum was extensively colonised by transplanted vagal NCC and the
      migration front had advanced caudorostrally to the level of the umbilicus. By
      E10, the stage at which sacral NCC begin to colonise the hindgut in large
      numbers, myenteric and submucosal plexuses in the hindgut almost entirely
      composed of transplanted vagal NCC, while the migration front had progressed into
      the pre-umbilical intestine, midway between the stomach and umbilicus.
      Immunohistochemical staining with the pan-neuronal marker, ANNA-1, revealed that
      the transplanted vagal NCC differentiated into enteric neurons, and whole-mount
      staining with NADPH-diaphorase showed that myenteric and submucosal ganglia
      formed interconnecting plexuses, similar to control animals. Furthermore, using
      an anti-RET antibody, widespread immunostaining was observed throughout the ENS,
      within a subpopulation of sacral NC-derived ENS precursors, and in the majority
      of transplanted vagal-to-sacral NCC. Our results demonstrate that: (1) a cell
      autonomous difference exists between the migration/signalling mechanisms used by
      sacral and vagal NCC, as transplanted vagal cells migrated along pathways
      normally followed by sacral cells, but did so in much larger numbers, earlier in
      development; (2) vagal NCC transplanted into the sacral neuraxis extensively
      colonised the hindgut, migrated in a caudorostral direction, differentiated into
      neuronal phenotypes, and formed enteric plexuses; (3) RET immunostaining occurred
      in vagal crest-derived ENS cells, the nerve of Remak and a subpopulation of
      sacral NCC within hindgut enteric ganglia.

PMID- 12050130
TI  - Transformation of shoots into roots in Arabidopsis embryos mutant at the TOPLESS
      locus.
AB  - We describe a novel phenotype in Arabidopsis embryos homozygous for the
      temperature-sensitive topless-1 mutation. This mutation causes the transformation
      of the shoot pole into a root. Developing topless embryos fail to express markers
      for the shoot apical meristem (SHOOT MERISTEMLESS and UNUSUAL FLORAL ORGANS) and
      the hypocotyl (KNAT1). By contrast, the pattern of expression of root markers is
      either duplicated (LENNY, J1092) or expanded (SCARECROW). Shifts of developing
      topless embryos between permissive and restrictive temperatures show that apical
      fates (cotyledons plus shoot apical meristem) can be transformed to basal fates
      (root) as late as transition stage. As the apical pole of transition stage
      embryos shows both morphological and molecular characteristics of shoot
      development, this demonstrates that the topless 1 mutation is capable of causing
      structures specified as shoot to be respecified as root. Finally, our experiments
      fail to show a clear link between auxin signal transduction and topless-1 mutant
      activity: the development of the apical root in topless mutant individuals is not
      dependent on the activity of the predicted auxin response factor MONOPTEROS nor
      is the expression of DR5, a proposed 'auxin maximum reporter', expanded in the
      apical domain of topless embryos.

PMID- 12050131
TI  - Fate map of the chicken neural plate at stage 4.
AB  - A detailed fate map was obtained for the early chick neural plate (stages 3d/4).
      Numerous overlapping plug grafts were performed upon New-cultured chick embryos,
      using fixable carboxyfluorescein diacetate succinimidyl ester to label donor
      chick tissue. The specimens were harvested 24 hours after grafting and reached in
      most cases stages 9-11 (early neural tube). The label was detected
      immunocytochemically in wholemounts, and cross-sections were later obtained. The
      positions of the graft-derived cells were classified first into sets of purely
      neural, purely non-neural and mixed grafts. Comparisons between these sets
      established the neural plate boundary at stages 3d/4. Further analysis
      categorized graft contributions to anteroposterior and dorsoventral subdivisions
      of the early neural tube, including data on the floor plate and the eye field.
      The rostral boundary of the neural plate was contained within the earliest
      expression domain of the Ganf gene, and the overall shape of the neural plate was
      contrasted and discussed with regard to the expression patterns of the genes
      Plato, Sox2, Otx2 and Dlx5 (and others reported in the literature) at stages
      3d/4.

PMID- 12050132
TI  - A novel Xenopus Smad-interacting forkhead transcription factor (XFast-3)
      cooperates with XFast-1 in regulating gastrulation movements.
AB  - In early Xenopus embryos, the prototypical XFast-1/Smad2/Smad4 complex ARF1 is
      induced at the Mix.2 ARE by activin overexpression. We have characterised ARF2, a
      related, but much more abundant, complex formed during gastrulation in response
      to endogenous TGFbeta family members and we have identified a novel Fast family
      member, XFast-3, as its transcription factor component. Endogenous ARF2
      efficiently competes out ARF1 at early gastrulation, due to the ability of XFast
      3 to interact with activated Smads with much higher affinity than XFast-1. We
      demonstrate that ARF1 and ARF2 are activated by distinct TGFbeta family members.
      Using morpholino antisense oligonucleotides to deplete levels of the constituent
      transcription factors XFast-1 and XFast-3 specifically, we demonstrate an
      important role for ARF1 and ARF2 in early Xenopus embryos in controlling the
      convergent extension movements of gastrulation.

PMID- 12050133
TI  - Six3-mediated auto repression and eye development requires its interaction with
      members of the Groucho-related family of co-repressors.
AB  - Recent findings suggest that Six3, a member of the evolutionarily conserved
      So/Six homeodomain family, plays an important role in vertebrate visual system
      development. However, little is known about the molecular mechanisms by which
      this function is accomplished. Although several members of the So/Six gene family
      interact with members of the eyes absent (Eya) gene family and function as
      transcriptional activators, Six3 does not interact with any known member of the
      Eya family. Here, we report that Grg4 and Grg5, mouse counterparts of the
      Drosophila transcriptional co-repressor Groucho, interact with mouse Six3 and its
      closely related member Six6, which may also be involved in vertebrate eye
      development. The specificity of the interaction was validated by co
      immunoprecipitation of Six3 and Grg4 complexes from cell lines. We also show that
      the interaction between Six3 and Grg5 requires the Q domain of Grg5 and a
      conserved phenylalanine residue present in an eh1-like motif located in the Six
      domain of Six3. The pattern of Grg5 expression in the mouse ventral forebrain and
      developing optic vesicles overlapped that previously reported for Six3 and Six6.
      Using PCR, we identified a specific DNA motif that is bound by Six3 and we
      demonstrated that Six3 acts as a potent transcriptional repressor upon its
      interaction with Groucho-related members. We also demonstrated that this
      interaction is required for Six3 auto repression. The biological significance of
      this interaction in the retina and lens was assessed by overexpression
      experiments using either wild type full-length Six3 cDNA or a mutated form of
      this gene in which the interaction with Groucho proteins was disrupted.
      Overexpression of wild type Six3 by in vivo retroviral infection of newborn rat
      retinae led to an altered photoreceptor phenotype, while the in ovo
      electroporation of chicken embryos resulted in failure of lens placode
      invagination and production of delta-crystallin-negative cells within the
      placode. These specific alterations were not seen when the mutated form of Six3
      cDNA was used in similar experimental approaches, indicating that Six3
      interaction with Groucho proteins plays an essential role in vertebrate eye
      development.

PMID- 12050134
TI  - Retinoic acid signalling in the zebrafish embryo is necessary during pre
      segmentation stages to pattern the anterior-posterior axis of the CNS and to
      induce a pectoral fin bud.
AB  - A number of studies have suggested that retinoic acid (RA) is an important signal
      for patterning the hindbrain, the branchial arches and the limb bud. Retinoic
      acid is thought to act on the posterior hindbrain and the limb buds at
      somitogenesis stages in chick and mouse embryos. Here we report a much earlier
      requirement for RA signalling during pre-segmentation stages for proper
      development of these structures in zebrafish. We present evidence that a RA
      signal is necessary during pre-segmentation stages for proper expression of the
      spinal cord markers hoxb5a and hoxb6b, suggesting an influence of RA on
      anteroposterior patterning of the neural plate posterior to the hindbrain. We
      report the identification and expression pattern of the zebrafish retinaldehyde
      dehydrogenase2 (raldh2/aldh1a2) gene. Raldh2 synthesises retinoic acid (RA) from
      its immediate precursor retinal. It is expressed in a highly ordered spatial and
      temporal fashion during gastrulation in the involuting mesoderm and during later
      embryogenesis in paraxial mesoderm, branchial arches, eyes and fin buds,
      suggesting the involvement of RA at different times of development in different
      functional contexts. Mapping of the raldh2 gene reveals close linkage to no-fin
      (nof), a newly discovered mutant lacking pectoral fins and cartilaginous gill
      arches. Cloning and functional tests of the wild-type and nof alleles of raldh2
      reveal that nof is a raldh2 mutant. By treating nof mutants with RA during
      different time windows and by making use of a retinoic acid receptor antagonist,
      we show that RA signalling during pre-segmentation stages is necessary for
      anteroposterior patterning in the CNS and for fin induction to occur.

PMID- 12050135
TI  - Tiling of the Drosophila epidermis by multidendritic sensory neurons.
AB  - Insect dendritic arborization (da) neurons provide an opportunity to examine how
      diverse dendrite morphologies and dendritic territories are established during
      development. We have examined the morphologies of Drosophila da neurons by using
      the MARCM (mosaic analysis with a repressible cell marker) system. We show that
      each of the 15 neurons per abdominal hemisegment spread dendrites to
      characteristic regions of the epidermis. We place these neurons into four
      distinct morphological classes distinguished primarily by their dendrite
      branching complexities. Some class assignments correlate with known proneural
      gene requirements as well as with central axonal projections. Our data indicate
      that cells within two morphological classes partition the body wall into
      distinct, non-overlapping territorial domains and thus are organized as separate
      tiled sensory systems. The dendritic domains of cells in different classes, by
      contrast, can overlap extensively. We have examined the cell-autonomous roles of
      starry night (stan) (also known as flamingo (fmi)) and sequoia (seq) in tiling.
      Neurons with these genes mutated generally terminate their dendritic fields at
      normal locations at the lateral margin and segment border, where they meet or
      approach the like dendrites of adjacent neurons. However, stan mutant neurons
      occasionally send sparsely branched processes beyond these territories that could
      potentially mix with adjacent like dendrites. Together, our data suggest that
      widespread tiling of the larval body wall involves interactions between growing
      dendritic processes and as yet unidentified signals that allow avoidance by like
      dendrites.

PMID- 12050136
TI  - Cytosolic phospholipase A2alpha is crucial [correction of A2alpha deficiency is
      crucial] for 'on-time' embryo implantation that directs subsequent development.
AB  - Cytosolic phospholipase A2alpha (cPLA2alpha) is a major provider of arachidonic
      acid (AA) for the cyclooxygenase (COX) system for the biosynthesis of
      prostaglandins (PGs). Female mice with the null mutation for Pla2g4a (cPLA2alpha)
      produce small litters and often exhibit pregnancy failures, although the cause(s)
      of these defects remains elusive. We show that the initiation of implantation is
      temporarily deferred in Pla2g4a-/- mice, shifting the normal 'window' of
      implantation and leading to retarded feto-placental development without apparent
      defects in decidual growth. Furthermore, cPLA2alpha deficiency results in
      aberrant uterine spacing of embryos. The deferred implantation and deranged
      gestational development in Pla2g4a-/- mice were significantly improved by
      exogenous PG administration. The results provide evidence that cPLA2alpha-derived
      AA is important for PG synthesis required for on-time implantation. This study in
      Pla2g4a-/- mice, together with the results of differential blastocyst transfers
      in wild-type mice provides the first evidence for a novel concept that a short
      delay in the initial attachment reaction creates a ripple effect propagating
      developmental anomalies during the subsequent course of pregnancy.

PMID- 12050138
TI  - The retinoic acid signaling pathway regulates anterior/posterior patterning in
      the nerve cord and pharynx of amphioxus, a chordate lacking neural crest.
AB  - Amphioxus, the closest living invertebrate relative of the vertebrates, has a
      notochord, segmental axial musculature, pharyngeal gill slits and dorsal hollow
      nerve cord, but lacks neural crest. In amphioxus, as in vertebrates, exogenous
      retinoic acid (RA) posteriorizes the embryo. The mouth and gill slits never form,
      AmphiPax1, which is normally downregulated where gill slits form, remains
      upregulated and AmphiHox1 expression shifts anteriorly in the nerve cord. To
      dissect the role of RA signaling in patterning chordate embryos, we have cloned
      the single retinoic acid receptor (AmphiRAR), retinoid X receptor (AmphiRXR) and
      an orphan receptor (AmphiTR2/4) from amphioxus. AmphiTR2/4 inhibits AmphiRAR
      AmphiRXR-mediated transactivation in the presence of RA by competing for DR5 or
      IR7 retinoic acid response elements (RAREs). The 5' untranslated region of
      AmphiTR2/4 contains an IR7 element, suggesting possible auto- and RA-regulation.
      The patterns of AmphiTR2/4 and AmphiRAR expression during embryogenesis are
      largely complementary: AmphiTR2/4 is strongly expressed in the cerebral vesicle
      (homologous to the diencephalon plus anterior midbrain), while AmphiRAR
      expression is high in the equivalent of the hindbrain and spinal cord. Similarly,
      while AmphiTR2/4 is expressed most strongly in the anterior and posterior thirds
      of the endoderm, the highest AmphiRAR expression is in the middle third.
      Expression of AmphiRAR is upregulated by exogenous RA and completely
      downregulated by the RA antagonist BMS009. Moreover, BMS009 expands the pharynx
      posteriorly; the first three gill slit primordia are elongated and shifted
      posteriorly, but do not penetrate, and additional, non-penetrating gill slit
      primordia are induced. Thus, in an organism without neural crest, initiation and
      penetration of gill slits appear to be separate events mediated by distinct
      levels of RA signaling in the pharyngeal endoderm. Although these compounds have
      little effect on levels of AmphiTR2/4 expression, RA shifts pharyngeal expression
      of AmphiTR2/4 anteriorly, while BMS009 extends it posteriorly. Collectively, our
      results suggest a model for anteroposterior patterning of the amphioxus nerve
      cord and pharynx, which is probably applicable to vertebrates as well, in which a
      low anterior level of AmphiRAR (caused, at least in part, by competitive
      inhibition by AmphiTR2/4) is necessary for patterning the forebrain and formation
      of gill slits, the posterior extent of both being set by a sharp increase in the
      level of AmphiRAR. Supplemental data available on-line

PMID- 12050137
TI  - beta8 integrins are required for vascular morphogenesis in mouse embryos.
AB  - In order to assess the in vivo function of integrins containing the beta8
      subunit, we have generated integrin beta8-deficient mice. Ablation of beta8
      results in embryonic or perinatal lethality with profound defects in vascular
      development. Sixty-five percent of integrin beta8-deficient embryos die at
      midgestation, with evidence of insufficient vascularization of the placenta and
      yolk sac. The remaining 35% die shortly after birth with extensive intracerebral
      hemorrhage. Examination of brain tissue from integrin beta8-deficient embryos
      reveals abnormal vascular morphogenesis resulting in distended and leaky
      capillary vessels, as well as aberrant brain capillary patterning. In addition,
      endothelial cell hyperplasia is found in these mutant brains. Expression studies
      show that integrin beta8 transcripts are localized in endodermal cells
      surrounding endothelium in the yolk sac and in periventricular cells of the
      neuroepithelium in the brain. We propose that integrin beta8 is required for
      vascular morphogenesis by providing proper cues for capillary growth in both yolk
      sac and embryonic brain. This study thus identifies a molecule crucial for
      vascular patterning in embryonic yolk sac and brain.

PMID- 12050139
TI  - A study of mesoderm patterning through the analysis of the regulation of Xmyf-5
      expression.
AB  - Xenopus laevis has been a particularly useful model organism for identifying
      factors involved in the induction and patterning of the mesoderm, however, much
      remains to be learned about how these factors interact. The myogenic
      transcription factor Xmyf-5 is the earliest known gene to be expressed
      specifically in the dorsolateral mesoderm of the gastrula, a domain that is
      established by the interaction of dorsal and ventral signals. For this reason, we
      have begun to investigate how the expression of Xmyf-5 is regulated. We have
      identified a 7.28 kb Xenopus tropicalis Xmyf-5 (Xtmyf-5) genomic DNA fragment
      that accurately recapitulates the expression of the endogenous gene. Deletion and
      mutational analysis has identified HBX2, an essential element, approximately 1.2
      kb upstream from the start of transcription, which is necessary for both
      activation and repression of Xtmyf-5 expression, implying that positional
      information is integrated at this site. Electrophoretic mobility shift assays
      demonstrate that HBX2 specifically interacts with gastrula stage embryonic
      extracts and that in vitro translated Xvent-1 protein binds to one of its
      functional motifs. Combined with gain- and loss-of-function experiments, the
      promoter analysis described here suggests that Xvent-1 functions to repress Xmyf
      5 expression in the ventral domain of the marginal zone. Furthermore, the
      identification of HBX2 provides a tool with which to identify other molecules
      involved in the regulation of Xmyf-5 expression during gastrulation.

PMID- 12050140
TI  - Hairy/E(spl)-related (Her) genes are central components of the segmentation
      oscillator and display redundancy with the Delta/Notch signaling pathway in the
      formation of anterior segmental boundaries in the zebrafish.
AB  - We have examined the expression of a Hairy/E(spl)-related (Her) gene, her7, in
      the zebrafish and show that its expression in the PSM cycles similarly to her1
      and deltaC. A decrease in her7 function generated by antisense oligonucleotides
      disrupts somite formation in the posterior trunk and tail, and disrupts the
      dynamic expression domains of her1 and deltaC, suggesting that her7 plays a role
      in coordinating the oscillations of neighboring cells in the presomitic mesoderm.
      This phenotype is reminiscent of zebrafish segmentation mutants with lesions in
      genes of the Delta/Notch signaling pathway, which also show a disruption of
      cyclic her7 expression. The interaction of HER genes with the Delta/Notch
      signaling system was investigated by introducing a loss of her7 function into
      mutant backgrounds. This leads to segmental defects more anterior than in either
      condition alone. Combining a decrease of her7 function with reduction of her1
      function results in an enhanced phenotype that affects all the anterior segments,
      indicating that Her functions in the anterior segments are also partially
      redundant. In these animals, gene expression does not cycle at any time,
      suggesting that a complete loss of oscillator function had been achieved.
      Consistent with this, combining a reduction of her7 and her1 function with a
      Delta/Notch mutant genotype does not worsen the phenotype further. Thus, our
      results identify members of the Her family of transcription factors that together
      behave as a central component of the oscillator, and not as an output. This
      indicates, therefore, that the function of the segmentation oscillator is
      restricted to the positioning of segmental boundaries. Furthermore, our data
      suggest that redundancy between Her genes and genes of the Delta/Notch pathway is
      in part responsible for the robust formation of anterior somites in vertebrates.

PMID- 12050141
TI  - Commissureless is required both in commissural neurones and midline cells for
      axon guidance across the midline.
AB  - In the absence of Commissureless (Comm) function, axons are unable to extend
      across the central nervous system midline. Comm downregulates levels of
      Roundabout (Robo), a receptor for the midline repellent Slit, in order to allow
      axons to cross the midline. comm transcript is expressed at high levels in the
      midline glia and Comm protein accumulates on axons at the midline. This has led
      to the hypothesis that Comm moves from the midline glia to the axons, where it
      can reduce Robo levels. We have found that expression of Comm in the midline
      cells is unable to rescue the comm phenotype and that tagged versions of Comm are
      not transferred to axons. A re-examination of Comm protein expression and the use
      of targeted RNA interference reveal that correct midline crossing requires that
      Comm is expressed in the commissural axons and midline glia. We suggest that
      accumulation of Comm protein at the midline spatially limits Comm activity and
      prevents it from being active on the contralateral side of the central nervous
      system.

PMID- 12050142
TI  - abdominal A specifies one cell type in Drosophila by regulating one principal
      target gene.
AB  - The Hox/homeotic genes encode transcription factors that generate segmental
      diversity during Drosophila development. At the level of the whole animal, they
      are believed to carry out this role by regulating a large number of downstream
      genes. Here we address the unresolved issue of how many Hox target genes are
      sufficient to define the identity of a single cell. We focus on the larval
      oenocyte, which is restricted to the abdomen and induced in response to a non
      cell autonomous, transient and highly selective input from abdominal A (abdA). We
      use Hox mutant rescue assays to demonstrate that this function of abdA can be
      reconstituted by providing Rhomboid (Rho), a processing factor for the EGF
      receptor ligand, secreted Spitz. Thus, in order to make an oenocyte, abdA
      regulates just one principal target, rho, that acts at the top of a complex
      hierarchy of cell-differentiation genes. These studies strongly suggest that, in
      at least some contexts, Hox genes directly control only a few functional targets
      within each nucleus. This raises the possibility that much of the overall Hox
      downstream complexity results from cascades of indirect regulation and cell-to
      cell heterogeneity.

PMID- 12050144
TI  - PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at
      multiple steps.
AB  - In developing murine growth plates, chondrocytes near the articular surface
      (periarticular chondrocytes) proliferate, differentiate into flat column-forming
      proliferating cells (columnar chondrocytes), stop dividing and finally
      differentiate into hypertrophic cells. Indian hedgehog (Ihh), which is
      predominantly expressed in prehypertrophic cells, stimulates expression of
      parathyroid hormone (PTH)-related peptide (PTHrP) which negatively regulates
      terminal chondrocyte differentiation through the PTH/PTHrP receptor (PPR).
      However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte
      differentiation are unclear. We present novel mouse models with PPR abnormalities
      that help clarify these roles. In mice with chondrocyte-specific PPR ablation and
      mice with reduced PPR expression, chondrocyte differentiation was accelerated not
      only at the terminal step but also at an earlier step: periarticular to columnar
      differentiation. In these models, upregulation of Ihh action in the periarticular
      region was also observed. In the third model in which the PPR was disrupted in
      about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes
      was upregulated because of ectopically differentiated hypertrophic chondrocytes
      that had lost PPR. Acceleration of periarticular to columnar differentiation was
      also noted in this mouse, while most of periarticular chondrocytes retained PPR
      signaling. These data suggest that Ihh positively controls differentiation of
      periarticular chondrocytes independently of PTHrP. Thus, chondrocyte
      differentiation is controlled at multiple steps by PTHrP and Ihh through the
      mutual regulation of their activities.

PMID- 12050143
TI  - Mechanisms of Gurken-dependent pipe regulation and the robustness of dorsoventral
      patterning in Drosophila.
AB  - The restriction of Pipe, a potential glycosaminoglycan-modifying enzyme, to
      ventral follicle cells of the egg chamber is essential for dorsoventral axis
      formation in the Drosophila embryo. pipe repression depends on the TGFalpha-like
      ligand Gurken, which activates the Drosophila EGF receptor in dorsal follicle
      cells. An analysis of Raf mutant clones shows that EGF signalling is required
      cell-autonomously in all dorsal follicle cells along the anteroposterior axis of
      the egg chamber to repress pipe. However, the autoactivation of EGF signalling
      important for dorsal follicle cell patterning has no influence on pipe
      expression. Clonal analysis shows that also the mirror-fringe cassette suggested
      to establish a secondary signalling centre in the follicular epithelium is not
      involved in pipe regulation. These findings support the view that the pipe domain
      is directly delimited by a long-range Gurken gradient. Pipe induces ventral cell
      fates in the embryo via activation of the Spatzle/Toll pathway. However, large
      dorsal patches of ectopic pipe expression induced by Raf clones rarely affect
      embryonic patterning if they are separated from the endogenous pipe domain. This
      indicates that potent inhibitory processes prevent pipe dependent Toll activation
      at the dorsal side of the egg.

PMID- 12050145
TI  - Generation of different fates from multipotent muscle stem cells.
AB  - Although neuronal and mesenchymal stem cells exhibit multipotentiality, this
      property has not previously been demonstrated for muscle stem cells. We now show
      that muscle satellite cells of adult mice are able to differentiate into
      osteoblasts, adipocytes and myotubes. Undifferentiated muscle progenitor cells
      derived from a single satellite cell co-expressed multiple determination genes
      including those for MyoD and Runx2, which are specific for myogenic and
      osteogenic differentiation, respectively. Determination genes not relevant to the
      induced differentiation pathway were specifically downregulated in these cells.
      Similar multipotent progenitor cells were isolated from adult human muscle. Based
      on these observations, we propose a 'stock options' model for the generation of
      different fates from multipotent stem cells.

PMID- 12050146
TI  - Epithelial cell cycling predicts p53 responsiveness to gamma-irradiation during
      post-natal mammary gland development.
AB  - The tumor suppressor gene, TP53, plays a major role in surveillance and repair of
      radiation-induced DNA damage. In multiple cell types, including mammary
      epithelial cells, abrogation of p53 (encoded by Trp53) function is associated
      with increased tumorigenesis. We examined gamma-irradiated BALB/c-Trp53(+/+) and 
      Trp53(-/-) female mice at five stages of post-natal mammary gland development to
      determine whether radiation-induced p53 activity is developmentally regulated.
      Our results show that p53-mediated responses are attenuated in glands from
      irradiated virgin and lactating mice, as measured by induction of p21/WAF1
      (encoded by Cdkn1a) and apoptosis, while irradiated early- and mid-pregnancy
      glands exhibit robust p53 activity. There is a strong correlation between p53
      mediated apoptosis and the degree of cellular proliferation, independent of the
      level of differentiation. In vivo, proliferation is intimately influenced by
      steroid hormones. To determine whether steroid hormones directly modulate p53
      activity, whole organ cultures of mammary glands were induced to proliferate
      using estrogen plus progesterone or epidermal growth factor plus transforming
      growth factor-alpha and p53 responses to gamma-irradiation were measured.
      Regardless of mitogens used, proliferating mammary epithelial cells show
      comparable p53 responses to gamma-irradiation, including expression of nuclear
      p53 and p21/WAF1 and increased levels of apoptosis, compared to non-proliferating
      irradiated control cultures. Our study suggests that differences in radiation
      induced p53 activity during post-natal mammary gland development are influenced
      by the proliferative state of the gland, and may be mediated indirectly by the
      mitogenic actions of steroid hormones in vivo.

PMID- 12050148
TI  - In vitro selection of external guide sequences for directing RNase P-mediated
      inhibition of viral gene expression.
AB  - External guide sequences (EGSs) are small RNA molecules that bind to a target
      mRNA, form a complex resembling the structure of a tRNA, and render the mRNA
      susceptible to hydrolysis by RNase P, a tRNA processing enzyme. An in vitro
      selection procedure was used to select EGSs that direct human RNase P to cleave
      the mRNA encoding thymidine kinase (TK) of herpes simplex virus 1. One of the
      selected EGSs, TK17, was at least 35 times more active in directing RNase P in
      cleaving TK mRNA in vitro than the EGS derived from a natural tRNA sequence.
      TK17, when in complex with the TK mRNA sequence, resembles a portion of tRNA
      structure and exhibits an enhanced binding affinity to the target mRNA. Moreover,
      a reduction of 95 and 50% in the TK expression was found in herpes simplex virus
      1-infected cells that expressed the selected EGS and the EGS derived from the
      natural tRNA sequence, respectively. Our study provides direct evidence that EGS
      molecules isolated by the selection procedure are effective in tissue culture.
      These results also demonstrate the potential for using the selection procedure as
      a general approach for the generation of highly effective EGSs for gene-targeting
      application.

PMID- 12050147
TI  - Disruption of acvrl1 increases endothelial cell number in zebrafish cranial
      vessels.
AB  - The zebrafish mutant violet beauregarde (vbg) can be identified at two days post
      fertilization by an abnormal circulation pattern in which most blood cells flow
      through a limited number of dilated cranial vessels and fail to perfuse the trunk
      and tail. This phenotype cannot be explained by caudal vessel abnormalities or by
      a defect in cranial vessel patterning, but instead stems from an increase in
      endothelial cell number in specific cranial vessels. We show that vbg encodes
      activin receptor-like kinase 1 (Acvrl1; also known as Alk1), a TGFbeta type I
      receptor that is expressed predominantly in the endothelium of the vessels that
      become dilated in vbg mutants. Thus, vbg provides a model for the human autosomal
      dominant disorder, hereditary hemorrhagic telangiectasia type 2, in which
      disruption of ACVRL1 causes vessel malformations that may result in hemorrhage or
      stroke. Movies available on-line

PMID- 12050149
TI  - Protein oxidation of cytochrome C by reactive halogen species enhances its
      peroxidase activity.
AB  - Reactive halogen species (RHS; X(2) and HOX, where X represents Cl, Br, or I) are
      metabolites mediated by neutrophil activation and its accompanying respiratory
      burst. We have investigated the interaction between RHS and mitochondrial
      cytochrome c (cyt c) by using electrospray mass spectrometry and electron spin
      resonance (ESR). When the purified cyt c was reacted with an excess amount of
      hypochlorous acid (HOCl) at pH 7.4, the peroxidase activity of cyt c was
      increased by 4.5-, 6.9-, and 8.6-fold at molar ratios (HOCl/cyt c) of 2, 4, and
      8, respectively. In comparison with native cyt c, the mass spectra obtained from
      the HOCl-treated cyt c revealed that oxygen is covalently incorporated into the
      protein as indicated by molecular ions of m/z = 12,360 (cyt c), 12,376 (cyt c +
      O), and 12,392 (cyt c + 2O). Using tandem mass spectrometry, a peptide (obtained
      from the tryptic digests of HOCl-treated cyt c) corresponding to the amino acid
      sequence MIFAGIK, which contains the methionine that binds to the heme, was
      identified to be involved in the oxygen incorporation. The location of the oxygen
      incorporation was unequivocally determined to be the methionine residue,
      suggesting that the oxidation of heme ligand (Met-80) by HOCl results in the
      enhancement of peroxidase activity of cyt c. ESR spectroscopy of HOCl-oxidized
      cyt c, when reacted with H(2)O(2) in the presence of the nitroso spin trap 2
      methyl-2-nitrosopropane (MNP), yielded more immobilized MNP/tyrosyl adduct than
      native cyt c. In the presence of H(2)O(2), the peroxidase activity of HOCl
      oxidized cyt c exhibited an increasing ability to oxidize tyrosine to tyrosyl
      radical as measured directly by fast flow ESR. Titration of both native cyt c and
      HOCl-oxidized cyt c with various amounts of H(2)O(2) indicated that the latter
      has a decreased apparent K(m) for H(2)O(2), implicating that protein oxidation of
      cyt c increases its accessibility to H(2)O(2). HOCl-oxidized cyt c also displayed
      an impaired ability to support oxygen consumption by the purified mitochondrial
      cytochrome c oxidase, suggesting that protein oxidation of cyt c may break the
      electron transport chain and inhibit energy transduction in mitochondria.

PMID- 12050150
TI  - Physical interaction between recombinational proteins Rhp51 and Rad22 in
      Schizosaccharomyces pombe.
AB  - In eukaryotes, Rad51 and Rad52 are two key components of homologous recombination
      and recombinational repair. These two proteins interact with each other. Here we
      investigated the role of interaction between Rhp51 and Rad22, the fission yeast
      homologs of Rad51 and Rad52, respectively, on the function of each protein. We
      identified a direct association between the two proteins and their self
      interactions both in vivo and in vitro. We also determined the binding domains of
      each protein that mediate these interactions. To characterize the role of Rhp51
      Rad22 interaction, we used random mutagenesis to identify the mutants Rhp51 and
      Rad22, which cannot interact each other. Interestingly, we found that mutant
      Rhp51 protein, which cannot interact with either Rad22 or Rti1 (G282D), lost its
      DNA repair ability. In contrast, mutant Rad22 proteins, which cannot specifically
      bind to Rhp51 (S379L and P381L), maintained their DNA repair ability. These
      results suggest that the interaction between Rhp51 and Rad22 is crucial for the
      recombinational repair function of Rhp51. However, the significance of this
      interaction on the function of Rad22 remains to be characterized further.

PMID- 12050151
TI  - Rapid nonvesicular transport of sterol between the plasma membrane domains of
      polarized hepatic cells.
AB  - We studied the transport of the fluorescent cholesterol analog dehydroergosterol
      (DHE) in polarized HepG2 human hepatoma cells. DHE delivered via methyl-beta
      cyclodextrin was delivered to both the apical and basolateral membranes and
      became concentrated in the apical membrane within 1 min. Intracellular DHE was
      targeted mainly to vesicles of the subapical compartment or apical recycling
      compartment (SAC/ARC), where it colocalized with fluorescent transferrin and
      fluorescent analogs of phosphatidylcholine and sphingomyelin. In contrast,
      transport of DHE from the plasma membrane to the trans-Golgi network was found to
      be very low. Vesicles containing DHE traversed the cells in both directions, but
      vesicular export of DHE from the SAC/ARC to the plasma membrane domains was low.
      Disruption of the microtubule cytoskeleton disturbed vesicular transport of DHE
      but not its enrichment in the apical (canalicular) membrane. Transport of DHE to
      the canalicular membrane after photobleaching was very rapid (t(12) = 1.6 min)
      and was largely ATP-independent in contrast to enrichment of DHE in the SAC/ARC.
      Release of DHE from the canalicular membrane was also ATP-independent but slower
      than the enrichment of sterol in the biliary canaliculus (t(12) = 5.4 min).
      Canalicular DHE could completely redistribute to the basolateral plasma membrane
      but could not transfer from one cell to the other cell of an HepG2 couplet. We
      conclude that sterol shuttles rapidly among the plasma membrane domains and other
      membrane organelles and that this nonvesicular pathway includes fast transbilayer
      migration.

PMID- 12050152
TI  - A novel transactivating factor that regulates interferon-gamma-dependent gene
      expression.
AB  - We have previously identified a novel interferon (IFN)-stimulated cis-acting
      enhancer element, gamma-IFN-activated transcriptional element (GATE). GATE
      differs from the known IFN-stimulated elements in its primary sequence.
      Preliminary analysis has indicated that the GATE-dependent transcriptional
      response requires the binding of novel transacting factors. A cDNA expression
      library derived from an IFN-gamma-stimulated murine macrophage cell line was
      screened with a (32)P-labeled GATE probe to identify the potential GATE-binding
      factors. A cDNA coding for a novel transcription-activating factor was
      identified. Based on its discovery, we named it as GATE-binding factor-1 (GBF-1).
      GBF-1 homologs are present in mouse, human, monkey, and Drosophila. It activates
      transcription from reporter genes carrying GATE. It possesses a strong
      transactivating activity but has a weak DNA binding property. GBF-1 is expressed
      in most tissues with relatively higher steady-state levels in heart, liver,
      kidney, and brain. Its expression is induced by IFN-gamma treatment. GBF-1 is
      present in both cytosolic and nuclear compartments. These studies thus identify a
      novel transactivating factor in IFN signaling pathways.

PMID- 12050153
TI  - Regulation of the epithelial sodium channel by N4WBP5A, a novel Nedd4/Nedd4-2
      interacting protein.
AB  - The amiloride-sensitive epithelial sodium channel (ENaC) plays a critical role in
      fluid and electrolyte homeostasis and consists of alpha, beta, and gamma
      subunits. The carboxyl terminus of each ENaC subunit contains a PPXY motif that
      is believed to be important for interaction with the WW domains of the ubiquitin
      protein ligases, Nedd4 and Nedd4-2. Disruption of this interaction, as in
      Liddle's syndrome where mutations delete or alter the PPXY motif of either the
      beta or gamma subunits, has been shown to result in increased ENaC activity and
      arterial hypertension. Here we present evidence that N4WBP5A, a novel Nedd4/Nedd4
      2-binding protein, is a potential regulator of ENaC. In Xenopus laevis oocytes
      N4WBP5A increases surface expression of ENaC by reducing the rate of ENaC
      retrieval. We further demonstrate that N4WBP5A prevents sodium feedback
      inhibition of ENaC possibly by interfering with the xNedd4-2-mediated regulation
      of ENaC. As N4WBP5A binds Nedd4/Nedd4-2 via PPXY motif/WW domain interactions and
      appears to be associated with specific intracellular vesicles, we propose that
      N4WBP5A functions by regulating Nedd4/Nedd4-2 availability and trafficking.
      Because N4WBP5A is highly expressed in native renal collecting duct and other
      tissues that express ENaC, it is a likely candidate to modulate ENaC function in
      vivo.

PMID- 12050154
TI  - Mutated human SOD1 causes dysfunction of oxidative phosphorylation in
      mitochondria of transgenic mice.
AB  - A growing body of evidence suggests that impaired mitochondrial energy production
      and increased oxidative radical damage to the mitochondria could be causally
      involved in motor neuron death in amyotrophic lateral sclerosis (ALS) and in
      familial ALS associated with mutations of Cu,Zn superoxide dismutase (SOD1). For
      example, morphologically abnormal mitochondria and impaired mitochondrial
      histoenzymatic respiratory chain activities have been described in motor neurons
      of patients with sporadic ALS. To investigate further the role of mitochondrial
      alterations in the pathogenesis of ALS, we studied mitochondria from transgenic
      mice expressing wild type and G93A mutated hSOD1. We found that a significant
      proportion of enzymatically active SOD1 was localized in the intermembrane space
      of mitochondria. Mitochondrial respiration, electron transfer chain, and ATP
      synthesis were severely defective in G93A mice at the time of onset of the
      disease. We also found evidence of oxidative damage to mitochondrial proteins and
      lipids. On the other hand, presymptomatic G93A transgenic mice and mice
      expressing the wild type form of hSOD1 did not show significant mitochondrial
      abnormalities. Our findings suggest that G93A-mutated hSOD1 in mitochondria may
      cause mitochondrial defects, which contribute to precipitating the
      neurodegenerative process in motor neurons.

PMID- 12050155
TI  - Hydropathic complementarity determines interaction of epitope (869)HITDTNNK(876)
      in Manduca sexta Bt-R(1) receptor with loop 2 of domain II of Bacillus
      thuringiensis Cry1A toxins.
AB  - In susceptible insects, Cry toxin specificity correlates with receptor
      recognition. In previous work, we characterized an scFv antibody (scFv73) that
      inhibits binding of Cry1A toxins to cadherin-like receptor. The CDR3 region of
      scFv73 shared homology with an 8-amino acid epitope ((869)HITDTNNK(876)) of the
      Manduca sexta cadherin-like receptor Bt-R(1) (Gomez, I., Oltean, D. I., Gill, S.
      S., Bravo, A., and Soberon, M. (2001) J. Biol. Chem. 276, 28906-28912). In this
      work, we show that the previous sequence of scFv73 CDR3 region was obtained from
      the noncoding DNA strand. However, most importantly, both scFv73 CDR3 amino acid
      sequences of the coding and noncoding DNA strands have similar binding
      capabilities to Cry1Ab toxin as Bt-R(1) (869)HITDTNNK(876) epitope, as
      demonstrated by the competition of scFv73 with binding to Cry1Ab with synthetic
      peptides with amino acid sequences corresponding to these regions. Using
      synthetic peptides corresponding to three exposed loop regions of domain II of
      Cry1Aa and Cry1Ab toxins, we found that loop 2 synthetic peptide competed with
      binding of scFv73 to Cry1A toxins in Western blot experiments. Also, loop 2
      mutations that affect toxicity of Cry1Ab toxin are affected in scFv73 binding.
      Toxin overlay assays of Cry1A toxins to M. sexta brush border membrane proteins
      showed that loop 2 synthetic peptides competed with binding of Cry1A toxins to
      cadherin-like Bt-R(1) receptor. These experiments identified loop 2 in domain II
      of as the cognate binding partner of Bt-R(1) (869)HITDTNNK(876). Finally, 10
      amino acids from beta-6-loop 2 region of Cry1Ab toxin ((363)SSTLYRRPFNI(373))
      showed hydropathic pattern complementarity to a 10-amino acid region of Bt-R(1)
      ((865)NITIHITDTNN(875)), suggesting that binding of Cry1A toxins to Bt-R(1) is
      determined by hydropathic complementarity and that the binding epitope of Bt-R(1)
      may be larger than the one identified by amino acid sequence similarity to
      scFv73.

PMID- 12050156
TI  - Surplus zinc is handled by Zym1 metallothionein and Zhf endoplasmic reticulum
      transporter in Schizosaccharomyces pombe.
AB  - Homeostatic mechanisms prevent the accumulation of free zinc in the cytoplasm,
      raising questions regarding where surplus zinc is stored and how it is delivered
      to and from these stores. A genetic screen for zinc hypersensitivity in
      Schizosaccharomyces pombe identified a missense mutation truncating Zhf, an
      endoplasmic reticulum transporter. These cells were approximately 5-fold more
      zinc-sensitive than other independent mutants. The targeted disruption of zhf
      prevented growth on low zinc medium and caused hypersensitivity to elevated
      zinc/cobalt but resistance to cadmium. The exposure to elevated zinc but not
      copper also promotes the accumulation of transcripts encoding a metallothionein
      designated Zym1. The Sty1 pathway is required for maximal zym1 expression but is
      not obligatory for zinc perception. The targeted disruption of zym1 impaired
      cadmium tolerance but only slightly impaired zinc tolerance, whereas zym1
      overexpression substantially rescued zinc hypersensitivity of zhf(-) cells. Four
      equivalents of zinc were displaced from Zym1 by up to 12 equivalents of p
      (hydroxymercuri)phenylsulphonate. Zym1 thiols react rapidly with 5,5'-dithiobis
      (2-nitrobenzoic acid) compared with bacterial zinc metallothionein (6.8 and 0.2 x
      10(-4) s(-1), respectively). Zym1 is unlike known fungal metallothioneins that
      are induced by and sequester copper but not zinc. Less zinc but normal cadmium
      was accumulated by zym1Delta, consistent with zinc sequestration by Zym1 in vivo.

PMID- 12050157
TI  - Cyclooxygenase-2 and presenilin-1 gene expression induced by interleukin-1beta
      and amyloid beta 42 peptide is potentiated by hypoxia in primary human neural
      cells.
AB  - Lipid messengers and amyloid beta (Abeta) peptides generated by cyclooxygenase-2
      (COX-2) and presenilin-1 (PS1) mediate pro-inflammatory signaling and neural
      degeneration in Alzheimer's disease (AD) brain. This study provides data showing
      that the COX-2 and PS1 genes each transcribe rare, highly labile RNA species that
      display early response gene behavior in human neural (HN) cells in primary
      culture, down-regulation during human neural development, and up-regulation in AD
      neocortex and hippocampal CA1. Together, interleukin-1beta and amyloid beta42
      peptide [IL-1beta+Abeta42] synergistically activated COX-2 and PS1 gene
      expression preceded by increases in AP1-, STAT1alpha-, and in particular NF
      kappaBp50/p65- and HIF-1alpha-DNA binding. These events were markedly potentiated
      by hypoxia and blocked by the antioxidant alpha-phenyl-N-tert-butyl nitrone.
      Broad transcription profiling further indicated that hypoxia-induced, [IL
      1beta+Abeta42]-treated HN cells display robust induction of COX-2 and PS1 as well
      as a pro-inflammatory gene family that includes NF-kappaBp50/p105, IL-1beta
      precursor, and cytosolic phospholipase A2 genes. These findings indicate a novel
      [IL-1beta+Abeta42]-mediated, hypoxia-enhanced, free radical-triggered gene
      program that drives inflammatory gene signaling and suggest a mechanism by which
      hypoxia during aging contributes episodically to amyloidogenesis, inflammation,
      and AD pathophysiology.

PMID- 12050158
TI  - Norepinephrine increases I kappa B alpha expression in astrocytes.
AB  - The neurotransmitter norepinephrine (NE) can inhibit inflammatory gene expression
      in glial cells; however, the mechanisms involved are not clear. In primary
      astrocytes, NE dose-dependently increased the expression of inhibitory I kappa B
      alpha protein accompanied by an increase in steady state levels of I kappa B
      alpha mRNA. Maximal increases were observed at 30-60 min for the mRNA and at 4 h
      for protein, and these effects were mediated by NE binding to beta-adrenergic
      receptors. NE activated a 1.3-kilobase I kappa B alpha promoter transfected into
      astrocytes or C6 glioma cells, and this activation was prevented by a beta
      antagonist and by protein kinase A inhibitors but not by an NF kappa B inhibitor.
      NE increased I kappa B alpha protein in both the cytosolic and the nuclear
      fractions, suggesting an increase in nuclear uptake of I kappa B alpha. I kappa B
      alpha was detected in the frontal cortex of normal adult rats, and its levels
      were reduced if central NE levels were depleted by lesion of the locus ceruleus.
      The reduction of brain I kappa B alpha levels was paralleled by increased
      inflammatory responses to lipopolysaccharide. These results demonstrate that I
      kappa B alpha expression is regulated by NE at both transcriptional and post
      transcriptional levels, which could contribute to the observed anti-inflammatory
      properties of NE in vitro and in vivo.

PMID- 12050159
TI  - Involvement of a plastid terminal oxidase in plastoquinone oxidation as evidenced
      by expression of the Arabidopsis thaliana enzyme in tobacco.
AB  - Chlororespiration has been defined as a respiratory electron transport chain in
      interaction with photosynthetic electron transport involving both non
      photochemical reduction and oxidation of plastoquinones. Different enzymatic
      activities, including a plastid-encoded NADH dehydrogenase complex, have been
      reported to be involved in the non-photochemical reduction of plastoquinones.
      However, the enzyme responsible for plasquinol oxidation has not yet been clearly
      identified. In order to determine whether the newly discovered plastid oxidase
      (PTOX) involved in carotenoid biosynthesis acts as a plastoquinol oxidase in
      higher plant chloroplasts, the Arabidopsis thaliana PTOX gene (At-PTOX) was
      expressed in tobacco under the control of a strong constitutive promoter. We
      showed that At-PTOX is functional in tobacco chloroplasts and strongly
      accelerates the non-photochemical reoxidation of plastoquinols; this effect was
      inhibited by propyl gallate, a known inhibitor of PTOX. During the dark to light
      induction phase of photosynthesis at low irradiances, At-PTOX drives significant
      electron flow to O(2), thus avoiding over-reduction of plastoquinones, when photo
      synthetic CO(2) assimilation was not fully induced. We proposed that PTOX, by
      modulating the redox state of intersystem electron carriers, may participate in
      the regulation of cyclic electron flow around photosystem I.

PMID- 12050160
TI  - The tumor suppressor protein TSLC1 is involved in cell-cell adhesion.
AB  - TSLC1 is a tumor suppressor gene encoding a member of the immunoglobulin (Ig)
      superfamily. The significant homology of its extracellular domain with those of
      other Ig superfamily cell adhesion molecules (IgCAMs) has raised the possibility
      that TSLC1 participates in cell-cell interactions. In this study, the
      physiological properties of TSLC1 were investigated in Madin-Darby canine kidney
      (MDCK) cells expressing TSLC1 tagged with green fluorescent protein (GFP) as well
      as in the cells that express endogenous TSLC1. Biochemical analysis has revealed
      that TSLC1 is an N-linked glycoprotein with a molecular mass of 75 kDa and that
      it forms homodimers through cis interaction within the plane of the cell
      membranes. Confocal laser scanning microcopy of the cells expressing TSLC1 showed
      the localization patterns characteristic to adhesion molecules. At the beginning
      of cell attachment, TSLC1 accumulated in interdigitated structures at cell-cell
      boundaries, but, when cells reached a confluence, TSLC1 was distributed all along
      the cell membranes. In polarized cells, TSLC1 was recruited to the lateral
      membrane, implying trans interaction of TSLC1 between neighboring cells. In
      support of this notion, MDCK cells expressing TSLC1-GFP showed a significant
      level of cell aggregation in the absence or presence of Ca(2+) and Mg(2+). Taken
      together, these results indicate that TSLC1 mediates intracellular adhesion
      through homophilic interactions in a Ca(2+)/Mg(2+)-independent manner.

PMID- 12050162
TI  - The nephroblastoma overexpressed gene (NOV/ccn3) protein associates with Notch1
      extracellular domain and inhibits myoblast differentiation via Notch signaling
      pathway.
AB  - We demonstrate a novel interaction of the nephroblastoma overexpressed gene
      (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV
      associates with the epidermal growth factor-like repeats of Notch1 by the CT (C
      terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the
      downstream transducers of Notch signaling, were activated by NOV. Expressions of
      NOV and Notch1 were concomitant in the presomitic mesoderm and later in the
      myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal
      cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to
      down-regulation of MyoD and myogenin, resulting in inhibition of myotube
      formation. These results indicate that NOV-Notch1 association exerts a positive
      effect on Notch signaling and consequently suppresses myogenesis.

PMID- 12050161
TI  - Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone
      receptor-mediated signaling in L beta T2 cells.
AB  - The hypothalamic hormone gonadotropin-releasing hormone (GnRH) stimulates the
      synthesis and release of the pituitary gonadotropins. GnRH acts through a plasma
      membrane receptor that is a member of the G protein-coupled receptor (GPCR)
      family. These receptors interact with heterotrimeric G proteins to initiate
      downstream signaling. In this study, we have investigated which G proteins are
      involved in GnRH receptor-mediated signaling in L beta T2 pituitary gonadotrope
      cells. We have shown previously that GnRH activates ERK and induces the c-fos and
      LH beta genes in these cells. Signaling via the G(i) subfamily of G proteins was
      excluded, as neither ERK activation nor c-Fos and LH beta induction was impaired
      by treatment with pertussis toxin or a cell-permeable peptide that sequesters G
      beta gamma-subunits. GnRH signaling was partially mimicked by adenoviral
      expression of a constitutively active mutant of G alpha(q) (Q209L) and was
      blocked by a cell-permeable peptide that uncouples G alpha(q) from GPCRs.
      Furthermore, chronic activation of G alpha(q) signaling induced a state of GnRH
      resistance. A cell-permeable peptide that uncouples G alpha(s) from receptors was
      also able to inhibit ERK, c-Fos, and LH beta, indicating that both G(q/11) and
      G(s) proteins are involved in signaling. Consistent with this, GnRH caused GTP
      loading on G(s) and G(q/11) and increased intracellular cAMP. Artificial
      elevation of cAMP with forskolin activated ERK and caused a partial induction of
      c-Fos. Finally, treatment of G alpha(q) (Q209L)-infected cells with forskolin
      enhanced the induction of c-Fos showing that the two pathways are independent and
      additive. Taken together, these results indicate that the GnRH receptor activates
      both G(q) and G(s) signaling to regulate gene expression in L beta T2 cells.

PMID- 12050163
TI  - Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications
      for AMPA receptor trafficking.
AB  - SAP97 is a modular protein composed of three PDZ domains, an SH3 domain, and a
      guanylate kinase-like domain. It has been implicated functionally in the assembly
      and structural stability of synaptic junctions as well as in the trafficking,
      recruitment, and localization of specific ion channels and neurotransmitter
      receptors. The N terminus of SAP97 (S97N) has been shown to play a key role in
      the selection of binding partners and the localization of SAP97 at adhesion
      sites, as well as the clustering of ion channels in heterologous cells. Using the
      S97N domain as bait in a yeast two-hybrid screen, we identified the minus-end
      directed actin-based motor, myosin VI, as an S97N binding partner. Moreover, in
      light membrane fractions prepared from rat brain, we found that myosin VI and
      SAP97 form a trimeric complex with the alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptor subunit, GluR1. These data suggest that SAP97 may
      serve as a molecular link between GluR1 and the actin-dependent motor protein
      myosin VI during the dynamic translocation of AMPA receptors to and from the
      postsynaptic plasma membrane.

PMID- 12050164
TI  - Identification of the bacteria-binding peptide domain on salivary agglutinin (gp
      340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily.
AB  - Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the
      scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/DMBT1 is
      known for its Streptococcus mutans agglutinating properties. This 300-400 kDa
      glycoprotein is composed of conserved peptide motifs: 14 SRCR domains that are
      separated by SRCR-interspersed domains (SIDs), 2 CUB (C1r/C1s Uegf Bmp1) domains,
      and a zona pellucida domain. We have searched for the peptide domains of
      agglutinin/DMBT1 responsible for bacteria binding. Digestion with endoproteinase
      Lys-C resulted in a protein fragment containing exclusively SRCR and SID domains
      that binds to S. mutans. To define more closely the S. mutans-binding domain,
      consensus-based peptides of the SRCR domains and SIDs were designed and
      synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the
      SID peptides bound to S. mutans. Strikingly, this peptide was also able to induce
      agglutination of S. mutans and a number of other bacteria. The repeated presence
      of this peptide in the native molecule endows agglutinin/DMBT1 with a general
      bacterial binding feature with a multivalent character. Moreover, our studies
      demonstrate for the first time that the polymorphic SRCR domains of salivary
      agglutinin/DMBT1 mediate ligand interactions.

PMID- 12050165
TI  - Identification of Saccharomyces cerevisiae isoleucyl-tRNA synthetase as a target
      of the G1-specific inhibitor Reveromycin A.
AB  - To dissect the action mechanism of reveromycin A (RM-A), a G(1)-specific
      inhibitor, a Saccharomyces cerevisiae dominant mutant specifically resistant to
      RM-A, was isolated from a strain in which the genes implicated in nonspecific
      multidrug resistance had been deleted. The mutant gene (YRR2-1) responsible for
      the resistance was identified as an allele of the ILS1 gene encoding tRNA(Ile)
      synthetase (IleRS). The activity of IleRS, but not several other aminoacyl-tRNA
      synthetases examined in wild type cell extract, was highly sensitive to RM-A
      (IC(50) = 8 ng/ml). The IleRS activity of the YRR2-1 mutant was 4-fold more
      resistant to the inhibitor compared with that of wild type. The mutation
      IleRS(N660D), near the KMSKS consensus sequence commonly found in the class I
      aminoacyl transferases, was found to be responsible for RM-A resistance.
      Moreover, overexpression of the ILS1 gene from a high-copy plasmid conferred RM-A
      resistance. These results indicated that IleRS is a target of RM-A in vivo. A
      defect of the GCN2 gene led to decreased RM-A resistance. IleRS inhibition by RM
      A led to transcriptional activation of the ILS1 gene via the Gcn2-Gcn4 general
      amino acid control pathway, and this autoregulation seemed to contribute to RM-A
      resistance.

PMID- 12050166
TI  - Involvement of DNase gamma in apoptosis associated with myogenic differentiation
      of C2C12 cells.
AB  - Nucleosomal DNA fragmentation is detected in myoblasts only when apoptosis is
      induced under differentiating conditions. However, the molecular mechanisms and
      the DNase responsible for the differentiation-dependent apoptotic DNA laddering
      are poorly understood. Here we show that a Ca(2+)/Mg(2+)-dependent endonuclease,
      DNase gamma, is induced in C2C12 myoblasts during myogenic differentiation and
      catalyzes apoptotic DNA fragmentation in differentiating myoblasts. A
      Ca(2+)/Mg(2+)-dependent, Zn(2+)-sensitive endonuclease activity appears in C2C12
      myoblasts during myogenic differentiation. The enzymatic properties of the
      inducible DNase were found to be quite similar to those of DNase I family of
      DNases. Reverse transcriptase-PCR analysis revealed that the induction of DNase
      gamma, a member of the DNase I family of DNases, is correlated with the
      appearance of inducible DNase activity. The induction of DNase gamma occurs
      simultaneously with myogenin induction but precedes the up-regulation of p21. A
      high level of DNase gamma expression was also detected in differentiated myotubes
      but not in skeletal muscle fibers in which DNase X is highly expressed. The role
      of DNase gamma in myoblast apoptosis was evaluated in the following experiments.
      Proliferating myoblasts acquire DNA ladder producing ability by the ectopic
      expression of DNase gamma, but not DNase X, suggesting that the expression level
      of DNase gamma is the determinant of the differentiation-dependent apoptotic DNA
      laddering observed in myoblasts. DNA fragmentation during differentiation-induced
      apoptosis is strongly suppressed by the antisense-mediated down-regulation of
      DNase gamma. Importantly, the extent of DNA laddering is well correlated with the
      level of endogenous DNase gamma activity. Our data demonstrate that DNase gamma
      is the endonuclease responsible for DNA fragmentation in apoptosis associated
      with myogenic differentiation.

PMID- 12050167
TI  - Cloning and characterization of a calcium-binding, histamine-releasing protein
      from Schistosoma mansoni.
AB  - A homologue of the mammalian translationally controlled tumor protein (TCTP) was
      cloned from the human parasite Schistosoma mansoni (SmTCTP). Sequence analysis
      showed that SmTCTP differed from other reported TCTPs in having only one
      signature sequence. Subsequently, SmTCTP was cloned in a T7 expression system and
      expressed as a histidine-tagged fusion protein. Recombinant SmTCTP (rSmTCTP) has
      a molecular mass of approximately 23 kDa with the histidine tag. Further analysis
      showed that SmTCTP transcripts and protein are expressed in all life cycle stages
      of the parasite within the vertebrate hosts. Interestingly, antibodies to SmTCTP
      were present in the sera of mice 9 weeks after infection with S. mansoni.
      Characterization studies showed that rSmTCTP is a calcium-binding protein that
      can cause histamine release from basophil/mast cells and induce eosinophil
      infiltration. These findings suggest that SmTCTP may have an important role in
      the development of allergic inflammatory responses associated with
      schistosomiasis and may be a target for new drug development.

PMID- 12050168
TI  - Trypsin-sensitive and lipid-containing sites of the macrophage extracellular
      matrix bind apolipoprotein A-I and participate in ABCA1-dependent cholesterol
      efflux.
AB  - A unique property of the extracellular matrix of J774 and THP-1 cells has been
      identified, which contributes to the ability of these cells to promote
      cholesterol efflux. We demonstrate high level apolipoprotein (apo) A-I binding to
      macrophage cells (THP-1 and J774) and to their extracellular matrix (ECM).
      However, high level apoA-I binding is not observed on fibroblasts, HepG2 cells,
      or U937 cells (a macrophage cell line that does not efflux cholesterol to apoA-I
      or bind apoA-I on their respective ECM). Binding to the ECM of THP-1 or J774
      macrophages depends on the presence of apoA-I C-terminal helices and is markedly
      reduced with a mutant lacking residues 187-243 (apoA-I Delta(187-243)),
      suggesting that the hydrophobic C terminus forms a hydrophobic interaction with
      the ECM. ApoA-I binding is lost upon trypsin treatment or with Triton X-100, a
      preparation method that de-lipidates the ECM. However, binding is recovered with
      re-lipidation, and is preserved with ECM prepared using cytochalasin B, which
      conserves the endogenous phospholipid levels of the ECM. We also demonstrate that
      specific cholesterol efflux to apoA-I is much reduced in cells released from
      their native ECM, but fully restored when ECM-depleted cells are added back to
      ECM in the presence of apoA-I. The apoA-I-mediated efflux is deficient in plated
      or suspension U937 macrophages, but is restored to high levels when the
      suspension U937 cells are reconstituted with the ECM of J774 cells. The ECM
      dependent activity was much reduced in the presence of glyburide, indicating
      participation of ABCA1 (ATP-binding cassette transporter 1) in the efflux
      mechanism. These studies establish a novel binding site for apoA-I on the
      macrophage ECM that may function together with ABCA1 in promoting cholesterol
      efflux.

PMID- 12050169
TI  - The physiological role of RNase T can be explained by its unusual substrate
      specificity.
AB  - Escherichia coli RNase T, the enzyme responsible for the end-turnover of tRNA and
      for the 3' maturation of 5 S and 23 S rRNAs and many other small, stable RNAs,
      was examined in detail with respect to its substrate specificity. The enzyme was
      found to be a single-strand-specific exoribonuclease that acts in the 3' to 5'
      direction in a non-processive manner. However, although other Escherichia coli
      exoribonucleases stop several nucleotides downstream of an RNA duplex, RNase T
      can digest RNA up to the first base pair. The presence of a free 3'-hydroxyl
      group is required for the enzyme to initiate digestion. Studies with RNA
      homopolymers and a variety of oligoribonucleotides revealed that RNase T displays
      an unusual base specificity, discriminating against pyrimidine and, particularly,
      C residues. Although RNase T appears to bind up to 10 nucleotides in its active
      site, its specificity is defined largely by the last 4 residues. A single 3'
      terminal C residue can reduce RNase T action by >100-fold, and 2-terminal C
      residues essentially stop the enzyme. In vivo, the substrates of RNase T are
      similar in that they all contain a double-stranded stem followed by a single
      stranded 3' overhang; yet, the action of RNase T on these substrates differs. The
      substrate specificity described here helps to explain why the different
      substrates yield different products, and why certain RNA molecules are not
      substrates at all.

PMID- 12050170
TI  - Functional domains and DNA-binding sequences of RFLAT-1/KLF13, a Kruppel-like
      transcription factor of activated T lymphocytes.
AB  - RFLAT-1/KLF13, a member of the Kruppel-like family of transcription factors, was
      identified as a transcription factor expressed 3-5 days after T lymphocyte
      activation. It binds to the promoter of the chemokine gene RANTES (regulated on
      activation normal T cell expressed and secreted) and regulates its "late"
      expression in activated T-cells. In this study, a series of experiments to define
      the functional domains of RFLAT-1/KLF13 were undertaken to further advance the
      understanding of the molecular mechanisms underlying transcriptional regulation
      by this factor. Using the GAL4 fusion system, distinct transcriptional activation
      and repression domains were identified. The RFLAT-1 minimum activation domain is
      localized to amino acids 1-35, whereas the repression domain resides in amino
      acids 67-168. Deletion analysis on the RFLAT-1 protein further supports these
      domain functions. The RFLAT-1 activation domain is similar to that of its closest
      family member, basic transcription element-binding protein 1. This domain is
      highly hydrophobic, and site-directed mutagenesis demonstrated that both
      negatively charged and hydrophobic residues are important for transactivation.
      The nuclear localization signal of RFLAT-1 was also identified using the RFLAT
      1/green fluorescence protein fusion approach. RFLAT-1 contains two potent,
      independent nuclear localization signals; one is immediately upstream of the zinc
      finger DNA-binding domain, and the other is within the zinc fingers. Using
      mutational analysis, we also determined that the critical binding sequence of
      RFLAT-1 is CTCCC. The intact CTCCC box on the RANTES promoter is necessary for
      RFLAT-1-mediated RANTES transcription and is also required for the synergy
      between RFLAT-1 and NF-kappaB proteins.

PMID- 12050171
TI  - Dephosphorylation of endothelial nitric-oxide synthase by vascular endothelial
      growth factor. Implications for the vascular responses to cyclosporin A.
AB  - The endothelial isoform of nitric-oxide synthase (eNOS) is a key determinant of
      vascular tone. eNOS, a Ca(2+)/camodulin-dependent enzyme, is also regulated by a
      variety of agonist-activated protein kinases, but the role and regulation of the
      protein phosphatase pathways involved in eNOS dephosphorylation are much less
      well understood. Treatment of endothelial cells with vascular endothelial growth
      factor (VEGF), a potent eNOS agonist, leads to the activation of calcineurin, a
      Ca(2+)/camodulin-dependent protein phosphatase. In these studies, we used a
      phosphorylation state-specific antibody to show that VEGF promotes
      dephosphorylation of eNOS at serine residue 116 in cultured endothelial cells.
      Cyclosporin A, an inhibitor of calcineurin, completely blocks VEGF-induced eNOS
      dephosphorylation; under identical conditions, cyclosporin A also inhibits VEGF
      induced eNOS activation. VEGF-induced eNOS dephosphorylation shows an EC(50) of 2
      ng/ml and is maximal 30 min after agonist addition. eNOS phosphorylation at
      serine 116 is completely blocked by the protein kinase C inhibitor calphostin but
      is blocked by neither wortmannin (an inhibitor of phosphatidylinositide 3-kinase)
      nor the MAP kinase pathway inhibitor U0126. A phosphorylation-deficient mutant of
      eNOS in which serine 116 is changed to an alanine residue (S116A) shows
      significantly enhanced enzyme activity compared with the wild-type enzyme. Taken
      together, these findings indicated that VEGF-induced eNOS dephosphorylation at
      serine 116 leads to enzyme activation. Cyclosporin A is widely used as an
      immunosuppressive drug for which hypertension is an important dose-limiting side
      effect. Our results suggest that cyclosporin A-induced hypertension may involve,
      at least in part, the attenuation of endothelium-derived NO production through a
      calcineurin-sensitive pathway regulating eNOS dephosphorylation.

PMID- 12050172
TI  - Human topoisomerase IIalpha possesses an intrinsic nucleic acid specificity for
      DNA ligation. Use of 5' covalently activated oligonucleotide substrates to study
      enzyme mechanism.
AB  - Despite the importance of topoisomerase II-mediated DNA ligation to the essential
      physiological functions of the enzyme, the mechanistic details of this important
      reaction are poorly understood. Because topoisomerase II normally does not
      release cleaved DNA molecules prior to ligation, it is not known whether all of
      the nucleic acid specificity of its cleavage/ligation cycle is embodied in DNA
      cleavage or whether ligation also contributes specificity to the enzyme. All
      currently available ligation assays require that topoisomerase II cleave the
      initial DNA substrate before rejoining can be monitored. Consequently, it has
      been impossible to examine the specificity of DNA ligation separately from that
      of scission. To address this issue, a cleavage-independent topoisomerase II DNA
      ligation assay was developed. This assay utilizes a nicked oligonucleotide whose
      5'-phosphate terminus at the nick has been activated by covalent attachment to
      the tyrosine mimic, p-nitrophenol. Human topoisomerase IIalpha and enzymes with
      active-site mutations that abrogated cleavage activity ligated the activated nick
      by catalyzing the direct attack of the terminal 3'-OH on the activated 5'
      phosphate. Results with different DNA sequences indicate that human topoisomerase
      IIalpha possesses an intrinsic nucleic acid specificity for ligation that
      parallels its specificity for DNA cleavage.

PMID- 12050173
TI  - Regulation, restriction, and reminiscences.

PMID- 12050174
TI  - Enzyme ingenuity in biological oxidations: a trail leading to cytochrome p450.

PMID- 12050175
TI  - Immune escape of tumors: apoptosis resistance and tumor counterattack.
AB  - Interactions between the immune system and malignant cells play an important role
      in tumorigenesis. Failure of the immune system to detect and reject transformed
      cells may lead to cancer development. Tumors use multiple mechanisms to escape
      from immune-mediated rejection. Many of these mechanisms are now known on a
      cellular and molecular level. Despite this knowledge, cancer immunotherapy is
      still not an established treatment in the clinic. This review discusses the
      immune escape mechanisms used by tumors with an emphasis on mechanisms related to
      apoptosis.

PMID- 12050176
TI  - DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of
      dendritic cell biology.
AB  - Dendritic cells (DC) are present in essentially every tissue where they operate
      at the interface of innate and acquired immunity by recognizing pathogens and
      presenting pathogen-derived peptides to T cells. It is becoming clear that not
      all C-type lectins on DC serve as antigen receptors recognizing pathogens through
      carbohydrate structures. The C-type lectin DC-SIGN is unique in that it regulates
      adhesion processes, such as DC trafficking and T-cell synapse formation, as well
      as antigen capture. Moreover, even though several C-type lectins have been shown
      to bind HIV-1, DC-SIGN does not only capture HIV-1 but also protects it in early
      endosomes allowing HIV-1 transport by DC to lymphoid tissues, where it enhances
      trans infection of T cells. Here we discuss the carbohydrate/protein recognition
      profile and other features of DC-SIGN that contribute to the potency of DC to
      control immunity.

PMID- 12050177
TI  - Rapid static adhesion of human naive neutrophil to naive xenoendothelium under
      physiologic flow is independent of Galalpha1,3-gal structures.
AB  - Adhesion interactions under flow have long been known to depend on applied wall
      shear stress. We investigated the ability of human naive neutrophils to adhere to
      xenogeneic endothelial cells under static and flow conditions. We demonstrate
      that human naive neutrophils bind to xenogeneic endothelial cells under flow
      conditions. This binding is dependent on the applied stress and is independent of
      Galalpha1,3-gal structures, ICAM-1, or its counter ligands LFA-1alpha and Mac-1.
      The binding was rapid and is characterized by stationary attachment with no
      obvious rolling or change in morphology. This binding leads to a transient
      increase in intracellular-free calcium levels in xenogeneic but not allogeneic
      endothelial cells with occasional oscillations that persist long after the
      initial contact between the two cell types. Previous activation of
      xenoendothelium by autologous serum or human TNF-alpha augments binding of human
      naive neutrophils to the endothelial cells. Our data suggest novel interaction
      sites between the xenogeneic endothelial cells and human naive neutrophils.

PMID- 12050178
TI  - Flt-3 ligand (FL) drives differentiation of rat bone marrow-derived dendritic
      cells expressing OX62 and/or CD161 (NKR-P1).
AB  - Bone marrow-derived dendritic cells (DC) of the rat have not been as well
      characterized as those from the mouse. Here, large quantities of bone marrow
      derived rat DC were generated when Flt-3 ligand (FL) was used as an adjunct to
      granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL
      4). These cells displayed a typical DC phenotype, expressing MHC class II, CD54,
      CD80, CD86, and CD11b/c. These DC also uniformly expressed low levels of CD161
      and expressed OX62 in a bimodal distribution. Few cells were recovered from
      cultures grown without FL, and they failed to express OX62 or CD161. The DC
      generated with FL were more potent antigen-presenting cells in mixed lymphocyte
      cultures than cells grown without FL, and among FL-derived cells, the OX62+ cells
      were slightly more stimulatory than OX62- cells. Thus, FL is a useful cytokine
      for obtaining large quantities of functional rat DC subsets in vitro.

PMID- 12050179
TI  - Potentiation by human serum of anti-inflammatory cytokine production by human
      macrophages in response to apoptotic cells.
AB  - Phagocytosis of apoptotic cells by macrophages leads to the production of anti
      inflammatory cytokines, thereby preventing inflammation. In this study, we
      demonstrate that human serum potentiates the production of anti-inflammatory
      cytokines, IL-10 and TGF-beta, by PMA-treated THP-1 cells and human monocyte
      derived macrophages in response to apoptotic cells, which results in great
      suppression of the production of proinflammatory cytokine IL-8. Human IgG but not
      its F(ab)'(2) suppressed the IL-8 production. Pretreatment of macrophages but not
      apoptotic cells with human serum or human IgG caused the suppression, suggesting
      that immune complex may not be formed with apoptotic cells. When FcgammaRI was
      specifically down-modulated by a monoclonal antibody, M22, the potentiating
      effects of human serum and human IgG on the anti-inflammatory cytokine production
      and the suppressive effects on IL-8 production were completely abolished. Thus,
      human IgG and FcgammaRI appear to be critical in leading to the production of
      anti-inflammatory cytokines by macrophage in response to apoptotic cells.

PMID- 12050180
TI  - Selective up-regulation of phospholipase C-beta2 during granulocytic
      differentiation of normal and leukemic hematopoietic progenitors.
AB  - In this study, we have investigated the expression of phospholipase C-beta2
      during the course of granulocytic differentiation of normal and malignant
      progenitors. As a model system, we used the NB4 cell line, a reliable in vitro
      model for the study of acute promyelocytic leukemia (APL), a variety of acute
      myeloid leukemia (AML) that responds to pharmacological doses of all trans
      retinoic acid (ATRA) by differentiating in a neutrophil-like manner. We found
      that PLC-beta2, virtually absent in untreated NB4 cells, was strongly up
      regulated after ATRA-induced granulocytic differentiation. Remarkably, using
      primary blasts purified from bone marrow of patients affected by APL successfully
      induced to remission by treatment with ATRA, we showed a striking correlation
      between the amount of PLC-beta2 expression and the responsiveness of APL blasts
      to the differentiative activity of ATRA. An increase of PLC-beta2 expression also
      characterized the cytokine-induced granulocytic differentiation of CD34+ normal
      hematopoietic progenitors. Taken together, these data show that PLC-beta2
      represents a sensitive and reliable marker of neutrophil maturation of normal and
      malignant myeloid progenitors. Moreover, PLC-beta2 levels can predict the in vivo
      responsiveness to ATRA of APL patients.

PMID- 12050181
TI  - Pulmonary eosinophilia in mice devoid of interleukin-5.
AB  - The biology of the eosinophilic leukocyte-development, recruitment, and prolonged
      existence in somatic tissues-has been linked almost invariably to the actions of
      the "eosinophil" cytokine, interleukin-5 (IL-5). Here we demonstrate that
      pulmonary eosinophilia can occur in the absence of IL-5, as morphologically
      normal eosinophils are recruited to the lungs of virus-infected IL-5 -/- mice
      with kinetics and sequelae that are indistinguishable from those of their IL-5
      +/+ counterparts. We conclude that pulmonary eosinophilia observed in response to
      primary paramyxovirus infection occurs via mechanisms that are distinct from
      those involved in eosinophil responses to allergens and in asthma. Furthermore,
      the presence of functional eosinophils in IL-5 -/- mice suggests the possibility
      of developmentally distinct subsets of what has been presumed to be a homogeneous
      leukocyte population.

PMID- 12050182
TI  - Compound exocytosis of granules in human neutrophils.
AB  - Human neutrophils are of prime importance for the immune defense. Recent data
      from eosinophils and pancreatic beta cells have indicated that granules, upon
      exocytosis, occasionally fuse with each other in the cytosol prior to their
      subsequent fusion with the plasma membrane. This is termed compound exocytosis.
      We therefore studied exocytosis of single granules from human neutrophils by the
      high-resolution cell-attached patch-clamp capacitance technique. We found that
      1.5% of the capacitance steps was greater than 5 fF, i.e., significantly larger
      than steps expected for exocytosis of single granules. The mean step size of
      these events was 20.5 fF, corresponding to compounds formed by at least five
      granules. The capacitance input from compound steps contributed more than 20% of
      the total capacitance increase. Electron microscopy captured morphological
      manifestations of transient exocytic events, confirming the functional results
      obtained by capacitance measurements. Compound exocytosis may be a mechanism for
      efficient targeting of release during exocytosis.

PMID- 12050183
TI  - Eicosapentaenoic acid inhibits CSF-induced human monocyte survival and maturation
      into macrophage through the stimulation of H2O2 production.
AB  - Human studies suggest a beneficial effect of eicosapentaenoic acid (EPA)
      supplemented diets on atherosclerotic and atherothrombotic disorders as well as
      autoimmune and inflammatory diseases and tumors. The effects of EPA on human
      monocyte survival and maturation into macrophage are not yet known. We studied
      the effects of EPA on the survival and development into macrophage of human
      monocyte treated with colony-stimulating factor (CSF). We have found that EPA
      induces cell death of the monocyte via apoptosis, even in the presence of M-CSF
      or GM-CSF, and inhibits differentiation from the monocyte to macrophage by
      inducing H2O2 production. In contrast to the effect of EPA on monocytes, EPA did
      not induce cell death of monocyte-derived macrophages. Such an apoptosis inducing
      effect on monocytes by EPA may contribute to the efficacy of EPA in
      atherosclerosis and autoimmune diseases.

PMID- 12050184
TI  - Bone marrow CD34+ progenitor cells stimulated with stem cell factor and GM-CSF
      have the capacity to activate IgD- B cells through direct cellular interaction.
AB  - Recent studies have suggested the involvement of bone marrow in the pathogenesis
      of rheumatoid arthritis (RA), in which proliferation of monocyte-lineage cells
      (MLC) as well as local B cell activation in the synovium play an important role.
      Here, we show that bone marrow-derived MLC have the capacity to activate human
      peripheral blood IgD- B cells. Bone marrow CD34+ cells from RA patients that had
      been stimulated with stem cell factor and GM-CSF for 3-4 weeks (>90% CD14+ HLA
      DR+ cells, <0.5% CD19+ B cells, and <0.5% CD3+ T cells; MLC) induced the
      production of IgG much more effectively than that of IgM by highly purified B
      cells from healthy donors in the presence of IL-2 and IL-10. CD34+ cells from
      cord blood or from bone marrow of osteoarthritis patients also displayed the
      capacity to induce IgG production. The induction of IgG production by the bone
      marrow-derived MLC was markedly decreased when they were separated from B cells
      by a membrane filter. The bone marrow-derived MLC interacted preferentially with
      IgD- B cells to induce IgG production. These results indicate that upon
      stimulation with stem cell factor and GM-CSF, CD34+ progenitor cells
      differentiate into MLC that activate preferentially IgD- B cells through direct
      cellular interactions to produce IgG. Therefore, the data suggest that the
      accelerated recruitment of MLC from the bone marrow to the synovium might play a
      role in the local B cell activation in RA.

PMID- 12050185
TI  - Wegener's granulomatosis: antiproteinase 3 antibodies induce monocyte cytokine
      and prostanoid release-role of autocrine cell activation.
AB  - Antineutrophil cytoplasmic antibodies (ANCA) targeting proteinase 3 [PR3;
      cytoplasmic ANCA (c-ANCA)], a leukocyte serine protease, are highly specific for
      Wegener's Granulomatosis (WG). A pathogenetic role for c-ANCA has been proposed
      as a result of their ability of activating neutrophils, whereas their interaction
      with monocytes is less well characterized. We investigated the influence of
      monoclonal anti-PR3 antibodies (anti-PR3) and c-ANCA from WG sera on monocyte
      cytokine and prostanoid release. We found that PR3 was expressed on the surface
      of isolated monocytes. Anti-PR3 challenge provoked a pronounced release of
      cytokines with early appearance of tumor necrosis factor alpha (TNF-alpha) and
      interleukin (IL)-1beta and delayed release of IL-6, IL-8, and thromboxane A2
      (TxA2). The secretory response was reproduced by c-ANCA but not by human and
      murine control IgG and anti-CD14 antibodies. Because F(ab)2 fragments of anti-PR3
      were ineffective, coligation of Fc gamma receptors (FcgammaR) was apparently
      mandatory for monocyte activation. Using soluble receptors for TNF-alpha and IL
      1beta and a Tx receptor antagonist, we noted that the "early" cytokines
      functioned as inducers of TxA2, which then activated IL-8 release. In contrast,
      IL-6 formation was an independent event. We concluded that anti-PR3 antibodies
      are potent inducers of monocyte cytokine and prostanoid release, and TNF-alpha,
      IL-1beta, and TxA2 function as facilitators of the secretory response. These
      mechanisms may contribute to inflammatory tissue injury in WG.

PMID- 12050186
TI  - Regulation of cyclooxygenase-2 by nitric oxide in activated hepatic macrophages
      during acute endotoxemia.
AB  - Eicosanoids generated via cyclooxygenase-2 (COX-2) and nitric oxide produced from
      inducible nitric oxide synthase (NOSII) have been implicated in endotoxin-induced
      tissue injury. In the present studies, we characterized COX-2 and NOSII activity
      in rat hepatic macrophages and their interaction during acute endotoxemia.
      Kupffer cells from control animals were found to constitutively express COX-2 and
      NOSII mRNA and protein. Whereas treatment of the cells with lipopolysaccharide
      (LPS) and/or interferon-gamma (IFN-gamma) had no major effect on COX-2, NOSII
      expression increased. Induction of acute endotoxemia resulted in a rapid and
      transient increase in constitutive COX-2 expression and prostaglandin E2 (PGE2)
      production by liver macrophages as well as NOSII expression and nitric oxide
      release. Cells from endotoxin-treated rats were also sensitized to generate more
      nitric oxide and express increased NOSII in response to LPS and IFN-gamma.
      Inhibition of NOSII with aminoguanidine reduced COX-2 mRNA and protein expression
      as well as PGE2 production by activated macrophages from endotoxemic, but not
      control animals. In contrast, SC236, a specific COX-2 inhibitor, had no effect on
      NOSII mRNA or protein levels or on nitric oxide production by hepatic
      macrophages, even after endotoxin administration. These data suggest that
      activation of COX-2 may be important in the pathophysiological response of
      hepatic macrophages to endotoxin. Moreover, nitric oxide is involved in
      regulating COX-2 in activated liver macrophages during acute endotoxemia.

PMID- 12050187
TI  - Oxidized low-density and high-density lipoproteins regulate the production of
      matrix metalloproteinase-1 and -9 by activated monocytes.
AB  - Monocytes/macrophages are prominent in atherosclerotic plaques where the vascular
      remodeling and plaque rupture may be influenced by the lipids and cytokines at
      these sites. Therefore, we evaluated the effects of factors found within the
      vascular wall, such as cytokines, oxidized low-density lipoprotein (ox-LDL), low
      density lipoprotein (LDL), and high-density lipoprotein (HDL), on monocyte
      derived matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9) and tissue inhibitor of
      metalloproteinases-1 (TIMP-1). ox-LDL, LDL, and HDL alone had no effect on MMP-1,
      MMP-9, or TIMP-1 production. However, in the presence of tumor necrosis factor
      (TNF)-alpha and GM-CSF, ox-LDL enhanced MMP-1 significantly by two- to threefold,
      increased MMP-9 slightly, and had no effect on TIMP-1 production. In contrast,
      HDL suppressed the induction of MMP-1 by TNF-alpha and GM-CSF as well as the ox
      LDL-mediated increase in MMP-1 production. The enhancement of MMP-1 production by
      ox-LDL occurred through, in part, a prostaglandin E2 (PGE2)-dependent pathway as
      indomethacin suppressed and PGE2 restored MMP-1 production. This conclusion was
      supported further by ox-LDL-mediated increases in PGE2 and cyclooxygenase-2 (COX
      2) production. These data suggest that the interaction of primary monocytes with
      ox-LDL and proinflammatory cytokines may contribute to vascular remodeling and
      plaque rupture.

PMID- 12050188
TI  - Increased responsiveness of murine eosinophils to MIP-1beta (CCL4) and TCA-3
      (CCL1) is mediated by their specific receptors, CCR5 and CCR8.
AB  - In the present study, we investigated the regulation of chemokine-mediated
      responses and receptor expression on eosinophils from mice. MIP-1alpha (CCL3) and
      eotaxin (CCL11) induced a significant and only partially overlapping
      intracellular calcium flux in antigen-elicited and peripheral blood eosinophils,
      and MCP-1 (CCL2), MDC (CCL22), MIP-1beta (CCL4), and TCA-3 (CCL1) did not. To
      demonstrate functional use of the specific receptors, we examined chemotactic
      responses. Peripheral blood eosinophils migrated toward MIP-1alpha (CCL3) and
      eotaxin (CCL11) but not MCP-1 (CCL2), MDC (CCL22), MIP-1beta (CCL4), and TCA-3
      (CCL1). Antigen-elicited eosinophils migrated toward MIP-1alpha (CCL3) and
      eotaxin (CCL11), but also migrated in response to MIP-1beta (CCL4) and TCA-3
      (CCL1), suggesting the up-regulation of additional chemokine receptors on antigen
      elicited eosinophils. The up-regulation of the additional chemokine-receptor
      responses appeared to be in part because of cytokine activation, because TNF
      alpha and/or IL-4 were able to up-regulate CCR1, -3, -5, and -8 mRNA expression
      in eosinophils as well as migration responses to the appropriate ligands. Using
      antibodies specific for CCR5 and CCR8, the chemotactic response to MIP-1beta and
      TCA-3, respectively, was reduced significantly. Finally, the expression of these
      new receptors appears to have an effect on activation and degranulation because
      MIP-1beta (CCL4) and TCA-3 (CCL1) induce significant levels of LTC4 from elicited
      eosinophils. These results suggest that eosinophils may up-regulate and use
      additional chemokine receptors during progression of inflammatory, allergic
      responses for migration and activation.

PMID- 12050189
TI  - Post-transcriptional regulation of TNF-alpha during in vitro differentiation of
      human monocytes/macrophages in primary culture.
AB  - Tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, is produced
      abundantly by monocytes and macrophages. We have compared LPS-stimulated TNF
      alpha production and regulation in freshly isolated human monocytes and
      macrophages differentiated in vitro. A significant increase in LPS-induced TNF
      alpha protein secretion was observed in macrophages over freshly isolated
      monocytes without comparable differences in TNF-alpha mRNA induction. Polysome
      gradient analysis showed polysome-mRNA distribution did not change, whereas TNF
      alpha mRNA stability increased in macrophages. Tristetraprolin mRNA expression
      was constitutive and decreased with differentiation-linked kinetics. Blockable
      LPS-inducible MAP kinase activity (p38, ERK) affected TNF-alpha biosynthesis
      differentially at the transcriptional and post-transcriptional level throughout
      the culture period. We suggest that the increase in TNF-alpha secretion in
      macrophages relates to changes in post-transcriptional processing, which is
      regulated indirectly by the expression of RNA-binding proteins. Changes in gene
      expression throughout monocytic differentiation equip the cell to act as a more
      potent producer of this proinflammatory cytokine.

PMID- 12050191
TI  - Protein kinase A regulates beta2 integrin avidity in neutrophils.
AB  - The adhesive phenotype of neutrophils (PMN) depends largely on activating and
      deactivating intracellular signals regulating beta2 integrin avidity for ligand.
      Our hypothesis is that PKA is a negative regulator of beta2 integrin avidity. In
      this work, we examined the role of PKA in PMN alphaMbeta2 integrin activation.
      Elevation of cAMP inhibited alphaMbeta2 integrin-dependent adhesion of PMN to
      immune complexes (IC), but not PMA-induced adhesion. The PKA inhibitor KT5720
      reversed the ability of cAMP to suppress adhesion to IC. Moreover, inhibition of
      PKA activity was sufficient to activate alphaMbeta2 integrin-dependent adhesion
      and increase beta2 integrin expression and binding of the monoclonal antibody
      CBRM1/5, which recognizes activated alphaMbeta2 specifically. However, PKA
      activity was necessary for sustained adhesion. Disruption of A kinase-anchoring,
      protein-PKA binding with a cell-permeant peptide derived from the AKAP Ht31 also
      activated adhesion. Unlike pharmacologic inhibition of PKA, AKAP peptide-induced
      adhesion was PKC dependent and did not affect beta2 integrin expression or
      CBRM1/5 binding. These data demonstrate that PKA appears to have a dual role in
      the mechanism regulating alphaMbeta2 integrin avidity and adhesion.

PMID- 12050190
TI  - In vitro assessment of chemokine receptor-ligand interactions mediating mouse
      eosinophil migration.
AB  - Eosinophil migration from circulation is controlled, in part, by chemokines
      through a family of G-protein-coupled chemokine receptors (CCR). Studies of human
      eosinophils have demonstrated that signaling through CCR3 receptors is a
      prominent pathway leading to chemotaxis, although several other receptor-ligand
      interactions also appear to mediate eosinophil recruitment. The availability of
      genetically unique strains of mice permits a reductionist approach to assess the
      signaling pathways in experimental models of human disease. However, despite
      similarities in these pathways between mice and humans, significant species
      differences exist, complicating the translation of results from animal models to
      humans. Purified mouse eosinophils were used in this study to investigate the
      chemokine receptor expression and the activities of 18 chemokines. Mouse
      eosinophils isolated from IL-5 transgenic mice expressed transcripts encoding the
      chemokine receptors CCR1, CCR2, CCR3, CCR5, CCR8, CXCR2, and CXCR4, but not CCR4.
      Mouse eosinophils also migrated in response to human and mouse eotaxin-1 and -2,
      but not human eotaxin-3. In addition, the induced migration of mouse eosinophils
      by TARC, MIP-1beta, and KC suggests that unidentified receptor-ligand
      interactions contribute to eosinophil recruitment. It is interesting that the
      potent chemoattractant of human eosinophils, RANTES, was unable to mediate mouse
      eosinophil migration. Furthermore, despite the ability of MIP-1alpha to bind
      receptors on purified mouse eosinophils, it was only able to induce significant
      eosinophil migration in a mixed splenocyte population and was unable to induce
      migration of highly purified eosinophils. Collectively, these observations reveal
      physiologically relevant distinctions in mechanisms mediating human and mouse
      eosinophil migration that potentially reflect evolutionary disparities between
      these species.

PMID- 12050192
TI  - Variable degrees of 1-alpha hydroxylase activity--fine tuning the rachitic
      rheostat.

PMID- 12050193
TI  - Novel gene mutations in patients with 1alpha-hydroxylase deficiency that confer
      partial enzyme activity in vitro.
AB  - The rate-limiting, hormonally regulated step in the biological activation of
      vitamin D is its 1alpha-hydroxylation to 1,25-dihydroxyvitamin D [1,25-(OH)(2)D]
      in the kidney, catalyzed by the mitochondrial cytochrome P450 enzyme,
      P450c1alpha. We previously cloned the human P450c1alpha cDNA and gene, and
      identified 14 different mutations, including 7 missense, in 19 patients with
      1alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1.
      None of the missense mutations encoded a protein with detectable enzymatic
      activity in vitro. Although there is phenotypic variation among such patients,
      the molecular basis of this variation is unknown. We analyzed 6 additional
      patients with clinical and radiographic features of rickets; in 4 patients the
      laboratory abnormalities were typical of 1alpha-hydroxylase deficiency, but in 2
      they were unusually mild [mild hypocalcemia and normal serum 1,25-(OH)(2)D
      concentration]. Direct sequencing revealed that all patients had P450c1alpha
      mutations on both alleles. Five new and 2 known mutations were identified. The
      new mutations included a 5-bp deletion with a 6-bp novel insertion causing a
      frameshift in exon 2, and a G to A change at +1 of intron 2; a minigene
      experiment proved that this intronic mutation prevented proper splicing. Three
      new missense mutations were found and tested by expressing the mutant cDNA in
      mouse Leydig MA-10 cells. The R389G mutant was totally inactive, but mutant L343F
      retained 2.3% of wild-type activity, and mutant E189G retained 22% of wild-type
      activity. The two mutations that confer partial enzyme activity in vitro were
      found in the 2 patents with mild laboratory abnormalities, suggesting that such
      mutations contribute to the phenotypic variation observed in patients with 1alpha
      hydroxylase deficiency.

PMID- 12050194
TI  - Functional genomics and proteomics in term and preterm parturition.

PMID- 12050195
TI  - Human myometrial genes are differentially expressed in labor: a suppression
      subtractive hybridization study.
AB  - Human parturition is effected by a cascade of factors, of which many are unknown.
      We aim to identify the genes that are changed by labor in the human myometrium by
      suppression subtractive hybridization. We also seek to ascertain whether these
      genes are differentially expressed in the myometrium at the upper or fundal and
      lower segments of the uterus. Term myometrial tissues were obtained from laboring
      and nonlaboring women undergoing cesarean section after obtaining informed
      consent. Total RNA was used in suppression subtractive hybridization (CLONTECH
      PCR Select) to produce two subtracted cDNA libraries enriched for genes expressed
      during or before labor, labor and not-in-labor libraries, respectively. Dot blot
      screening of 400 positive clones, constituting 20% of the two subtracted
      libraries, revealed 30 differentially expressed clones, 14 of which were up
      regulated by labor. Among the 10 known genes that were up-regulated in labor, 6
      had apparent immune regulatory and inflammatory roles. Three are well-known
      inflammatory mediators and modulators that were previously linked with
      parturition: IL-8, manganese superoxide dismutase (MnSOD), and metalloproteinase
      9. Three others, interferon-inducible 1-8d gene, elongation factor 1alpha, and
      nucleophosmin, have not been previously linked with labor. Constitutively
      expressed genes, including cyclophilin and alpha-actin, were found to be altered
      by labor. Quantitative real-time RT-PCR using Taqman probes further confirmed the
      up-regulation of some of these genes. The amounts of the specific genes assayed
      were standardized to 18S ribosomal RNA and are expressed as mean +/- SEM.
      Quantitative real-time RT-PCR showed that IL-8 mRNA rose from 0.003 +/- 0.002 in
      nonlaboring samples (n = 38) to 0.24 +/- 0.11 (n = 20) in gestational-age-matched
      spontaneously laboring women (P = 0.035). Similarly, MnSOD rose from 0.11 +/-
      0.02 (n = 24) to 1.23 +/- 0.56 (n = 24) in gestational-age-matched women (P =
      0.047). Additionally, cyclophilin, often used as a constitutive or housekeeping
      gene marker, increased from 0.0008 +/- 0.0002 (n = 6) to 0.002 +/- 0.0004 (n = 6;
      P = 0.008) during labor. Notably, MnSOD mRNA was differentially distributed
      between the upper (0.63 +/- 0.18) and lower (0.15 +/- 0.05; n = 15; P = 0.022)
      segments of the uterus, but IL-8 was not (n = 17; P = 0.97). Induced labor
      further showed significantly higher levels of IL-8 (0.63 +/- 0.21; n = 14) than
      spontaneous labor (0.22 +/- 0.11; n = 20; P = 0.046), but not MnSOD (P = 0.1).
      This work identifies novel as well as known genes that were not previously
      associated with parturition. It extends previous data indicating that there is
      differential expression of some, but not all genes within the gravid human
      uterus. Inflammatory genes constitute a major proportion of the known genes found
      to be up-regulated in labor, lending support to the hypothesis of an inflammatory
      mechanism for human parturition. This work further indicates that many factors
      associated with human labor and their complex interactions remain to be
      elucidated.

PMID- 12050196
TI  - Primary infertility in 45-year-old man with untreated 21-hydroxylase deficiency:
      successful outcome with glucocorticoid therapy.
AB  - We describe a 45-yr-old man, who presented with primary infertility of 2 yr. He
      had small testicles with severe oligoasthenozoospermia and low serum
      gonadotropins, but normal serum T. The suppression of gonadotropin secretion by
      increased adrenal steroids due to untreated 21-hydroxylase deficiency appeared to
      underlie the failure in spermatogenesis. Hydrocortisone treatment was started and
      was modified later to include prednisolone to get optimal suppression of the
      secretion of ACTH and adrenal steroids. Within a few months, the gonadotropin
      levels became normal, and spermatogenesis was improved. A normal pregnancy was
      achieved.

PMID- 12050198
TI  - Genetic causes of human reproductive disease.

PMID- 12050199
TI  - The genetics of hereditary nonmedullary thyroid carcinoma.

PMID- 12050200
TI  - Genetic control of susceptibility to osteoporosis.
AB  - Osteoporosis is a common disease with a strong genetic component. Twin studies
      have shown that genetic factors play an important role in regulating bone mineral
      density (BMD), ultrasound properties of bone, skeletal geometry, and bone
      turnover as well as contributing to the pathogenesis of osteoporotic fracture
      itself. These phenotypes are determined by the combined effects of several genes
      and environmental influences, but occasionally, osteoporosis or unusually high
      bone mass can occur as the result of mutations in a single gene. Examples are the
      osteoporosis-pseudoglioma syndrome, caused by inactivating mutations in the
      lipoprotein receptor-related protein 5 gene and the high bone mass syndrome,
      caused by activating mutations of the same gene. Genome-wide linkage studies in
      man have identified loci on chromosomes 1p36, 1q21, 2p21, 5q33-35, 6p11-12, and
      11q12-13 that show definite or probable linkage to BMD, but so far, the causative
      genes remain to be identified. Linkage studies in mice have similarly identified
      several loci that regulate BMD, and a future challenge will be to investigate the
      syntenic loci in humans. A great deal of research has been done on candidate
      genes; among the best studied are the vitamin D receptor and the collagen type I
      alpha 1 gene. Polymorphisms of vitamin D receptor have been associated with bone
      mass in several studies, and there is evidence to suggest that this association
      may be modified by dietary calcium and vitamin D intake. A functional
      polymorphism affecting an Sp1 binding site has been identified in the collagen
      type I alpha 1 gene that predicts osteoporotic fractures independently of bone
      mass by influencing collagen gene regulation and bone quality. An important
      problem with most candidate gene studies is small sample size, and this has led
      to conflicting results in different populations. Some researchers are exploring
      the use of meta-analysis to try and address this issue and gain an accurate
      estimate of effect size for different polymorphisms in relation to relevant
      clinical endpoints, such as BMD and fracture. From a clinical standpoint,
      advances in knowledge about the genetic basis of osteoporosis are important,
      because they offer the prospect of developing genetic markers for the assessment
      of fracture risk and the opportunity to identify molecules that will be used as
      targets for the design of new drugs for the prevention and treatment of bone
      disease.

PMID- 12050201
TI  - Molecular pathogenesis of hypophosphatemic rickets.

PMID- 12050202
TI  - Protein-tyrosine phosphatases: emerging targets for therapeutic intervention in
      type 2 diabetes and related states of insulin resistance.

PMID- 12050203
TI  - Clinical review 148: Monogenic disorders of puberty.

PMID- 12050204
TI  - Pharmacogenomics in endocrinology.

PMID- 12050206
TI  - Mutant luteinizing hormone receptors in a compound heterozygous patient with
      complete Leydig cell hypoplasia: abnormal processing causes signaling deficiency.
AB  - Over the past 5 yr several inactivating mutations in the LH receptor gene have
      been demonstrated to cause Leydig cell hypoplasia, a rare autosomal recessive
      form of male pseudohermaphroditism. Here, we report the identification of two new
      LH receptor mutations in a compound heterozygous case of complete Leydig
      hypoplasia and determine the cause of the signaling deficiency at a molecular
      level. On the paternal allele of the patient we identified in codon 343 a T to A
      transversion that changes a conserved cysteine in the hinge region of the
      receptor to serine (C343S); on the maternal allele a T to C transition causes
      another conserved cysteine at codon 543 in trans-membrane segment 5 to be altered
      to arginine (C543R). Both of these mutant receptors are completely devoid of
      hormone-induced cAMP reporter gene activation. Using Western blotting of
      expressed LH receptor protein with a hemagglutinin tag, we further show that
      despite complete absence of total and cell surface hormone binding, protein
      levels of both mutant LH receptors are only moderately affected. The expression
      and study of enhanced green fluorescent protein-tagged receptors confirmed this
      view and further indicated that initial translocation to the endoplasmic
      reticulum of these mutant receptors is normal. After that, however, translocation
      is halted or misrouted, and as a result, neither mutant ever reaches the cell
      surface, and they cannot bind hormone. This lack of processing is also indicated
      by reduced presence of an 80-kDa protein, the only N-linked glycosylated protein
      in the LH receptor protein profile. Thus, complete lack of signaling by the
      identified mutant LH receptors is caused by insufficient processing from the
      endoplasmic reticulum to the cell surface and results in complete Leydig cell
      hypoplasia in this patient.

PMID- 12050205
TI  - An unusual phenotype of Frasier syndrome due to IVS9 +4C>T mutation in the WT1
      gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis.
AB  - The Wilms' tumor gene (WT1) encodes a zinc-finger transcription factor involved
      in the development of the kidneys and gonads and their subsequent normal
      function. Mutations in the WT1 gene were identified in patients with WAGR (Wilms'
      tumor, aniridria, genitourinary abnormalities, and mental retardation), Denys
      Drash syndrome, and Frasier syndrome (FS). Constitutional heterozygous mutations
      of the WT1 gene, almost all located at intron 9, are found in patients with FS.
      This syndrome is characterized by female external genitalia in 46,XY patients,
      late renal failure, streak gonads, and high risk of gonadoblastoma development.
      We report a male with FS with an unusual phenotype characterized by normal penis
      size with perineal hypospadias, end-stage renal failure at the age of 19 yr,
      normal adult male serum T levels, extremely elevated gonadotropin levels, para
      testicular leiomyoma, unilateral testicular germ cell tumor, bilateral
      gonadoblastoma, and absence of gonadal dysgenesis. Automatic sequencing
      identified the IVS9 +4C>T mutation in the WT1 gene, which predicts a change in
      splice site utilization. WT1 transcript analysis showed reversal of the normal
      positive/negative KTS (lysine, threonine, and serine) isoform ratio, confirming
      the diagnosis of FS. This patient with FS presents an external genitalia of Denys
      Drash syndrome, suggesting that these two syndromes are not distinct diseases but
      may represent two ends of a spectrum of disorders caused by alterations in WT1
      gene. This case expands the spectrum of phenotypes associated with WT1 mutations,
      by including predominantly male ambiguous genitalia and absence of gonadal
      dysgenesis, extremely high gonadotropin levels, and delayed adrenarche, and
      presence of a para-testicular leiomyoma, bilateral gonadoblastoma, and germ cell
      neoplasia.

PMID- 12050207
TI  - Long-term progestin treatment inhibits RANTES (regulated on activation, normal T
      cell expressed and secreted) gene expression in human endometrial stromal cells.
AB  - RANTES (regulated on activation, normal T cell expressed and secreted) is
      synthesized by endometrial and endometriotic stromal cells and circulates in
      peritoneal fluid. Reports indicate that medroxyprogesterone acetate (MPA) is
      clinically effective in alleviating pelvic pain in the majority of endometriosis
      patients, which leads us to hypothesize that MPA may be antiinflammatory.
      Prolonged treatment (8 d) with MPA resulted in 36% and 50% decreases in
      luciferase activity and RANTES protein production, respectively, whereas shorter
      treatment (2 or 4 d) with MPA had no significant effect. We also observed that 8
      d of MPA increased PR expression. Both effects were blocked by RU486.
      Cotransfection of endometrial stromal cells with PR enhanced the effects mediated
      by endogenous PR. In addition, its action via progesterone response element cis
      elements, PR appeared to inhibit trans-activation of a nuclear factor-kappaB
      responsive element, further suppressing RANTES expression. These studies indicate
      that prolonged progestin exposure down-regulates endometrial RANTES gene
      transcription in vitro. The effect is PR dependent and mediated in part through a
      nuclear factor-kappaB pathway. The clinical effectiveness of chronic progestin
      treatment in endometriosis-associated pelvic pain may be attributed to its
      inhibition of RANTES production and its suppression of inflammatory responses in
      the pelvis.

PMID- 12050208
TI  - Human resistin gene: molecular scanning and evaluation of association with
      insulin sensitivity and type 2 diabetes in Caucasians.
AB  - Insulin resistance is strongly associated with obesity, but even among obese
      subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone,
      resistin, was identified, shown to reduce insulin-mediated glucose uptake, and
      shown to be increased in obese mice. We used the chromosome 19 draft sequence to
      determine the genomic structure of human resistin and to screen the exons,
      introns, and flanking sequences for variation. We screened 44 subjects with type
      2 diabetes and 20 nondiabetic family members who were at the extremes of insulin
      sensitivity. We identified eight noncoding single nucleotide polymorphisms (SNPs)
      and one GAT microsatellite repeat. Three SNPs, which were in incomplete linkage
      disequilibrium with each other and had allelic frequencies exceeding 5%, were
      selected for further study. No SNP was associated with type 2 diabetes, but the
      SNP in the promoter region was a significant determinant of insulin sensitivity
      index (P = 0.04) among nondiabetic family members who had undergone iv glucose
      tolerance tests. The three common SNPs showed statistical significance as
      determinants of insulin sensitivity index (P < 0.01) in interaction with body
      mass index. Noncoding SNPs in the resistin gene may influence insulin sensitivity
      in interaction with obesity, but this finding will need to be confirmed in other
      populations.

PMID- 12050209
TI  - ONYX-015, an E1B gene-defective adenovirus, induces cell death in human
      anaplastic thyroid carcinoma cell lines.
AB  - Being one of the most lethal human neoplasms and refractory to such conventional
      treatment as chemo- and radiotherapy, anaplastic thyroid carcinoma is a prime
      target for innovative therapy. p53 gene inactivation is a constant feature of
      this neoplasia. Therefore, we evaluated a therapeutic approach based on an E1B 55
      kDa gene-defective adenovirus (ONYX-015) that replicates only in cells with
      impaired p53 function and leads to cell death. Here we report that the ONYX-015
      virus induces cell death in three human thyroid anaplastic carcinoma cell lines
      (ARO, FRO, and KAT-4). In addition, we found that the growth of xenograft tumors
      induced in athymic mice by the injection of ARO cells was drastically reduced by
      ONYX-015 treatment. The ONYX-015 virus worked synergistically with two
      antineoplastic drugs (doxorubicin and paclitaxel) in inducing ARO and KAT-4 cell
      death. These results suggest that ONYX-015 may be a valid tool in the treatment
      of the human thyroid anaplastic carcinoma.

PMID- 12050210
TI  - Nine novel mutations in maturity-onset diabetes of the young (MODY) candidate
      genes in 22 Spanish families.
AB  - The aims of this study were to estimate the prevalence of major maturity-onset
      diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze
      genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and
      97 relatives were screened for mutations in the coding region of the glucokinase
      (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single
      strand conformation polymorphism and/or direct sequencing. In families carrying
      GCK mutations, the influence of genetic defects on fetal growth was investigated
      by comparing the birth weights of 32 offspring discordant for the mutations.
      Mutations in MODY genes were identified in 64% of the families. GCK/MODY2
      mutations were the most frequently found, in 41%: seven novel (R369P, S411F,
      M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four
      pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a
      previously unreported change (R271G). One family (4%) carried a novel mutation in
      the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1
      pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2
      index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2
      and was invariably present in MODY3 index patients. Chronic complications of
      diabetes were absent in the MODY2 population and were present in more than 40% of
      all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal
      mutation when the mutation was of paternal origin. The MODY1 patient was
      diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite
      good metabolic control, and severe late-onset complications were common within
      her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in
      our population as recruited from pediatric and adolescent index patients. The
      inheritance of GCK defects by the fetus results in a reduction of birth weight.
      Clinical expression of MODY3 and MODY1 mutations, the second and third groups of
      defects found, was more severe, including the frequent development of chronic
      complications.

PMID- 12050211
TI  - Overexpression of aromatase P450 in leiomyoma tissue is driven primarily through
      promoter I.4 of the aromatase P450 gene (CYP19).
AB  - The CYP19 gene encoding aromatase P450 (estrogen synthetase) is expressed in
      several extragonadal sites and regulated in a tissue-specific fashion, which is
      achieved by alternative use of the seven different promoters (and corresponding
      exons 1) of the CYP19 gene. Previously, we demonstrated that aromatase P450 is
      overexpressed in leiomyoma tissue and that in situ estrogen synthesized in
      leiomyoma tissues possibly plays a role in leiomyoma growth. To elucidate the
      mechanism of overexpression of aromatase P450, we determined the promoter use of
      aromatase P450 in leiomyomas. 5'-Rapid amplification of cDNA ends analysis
      revealed that of six leiomyoma nodules tested, four nodules contained I.4
      specific transcript of aromatase P450 alone, one nodule contained PII-specific
      transcript alone, and the remaining nodule contained both I.4- and PII-specific
      transcripts simultaneously. The levels of aromatase transcripts were then
      quantified by competitive RT-PCR assay. Among 21 leiomyomas, I.4-specific
      transcript and PII-specific transcript were predominant in 18 and 2 leiomyomas,
      respectively, whereas the remaining leiomyoma was negative for aromatase P450
      expression. We next compared the aromatase activity of leiomyoma cells stimulated
      by promoter-specific regulatory factors. A combination of IL-1beta and
      dexamethasone, known as a potent inducer of promoter I.4-driven transcription,
      effectively increased aromatase activity. A combination of (Bt)(2)cAMP, 3
      isobutyl-1-myethylxanthine, and PGE(2), known as inducers of promoter II-driven
      transcription, also increased aromatase activity, but the increases found were
      smaller than that induced by dexamethasone and IL-1beta. The transcriptional
      ability of the promoter I.4 sequence was confirmed by transient transfection
      assay using primary cells released from leiomyomas and established cells from
      normal myometrium (KW cells). Luciferase vectors containing promoter I.4 sequence
      (-340/+14 or longer) showed a significant increase in luciferase activity in
      response to dexamethasone. Deletion or mutation of a putative glucocorticoid
      responsive element in the promoter I.4 sequence eliminated promoter activity.
      These results indicate that promoter I.4 is the major promoter responsible for
      overexpression of aromatase P450 in leiomyomas and that a glucocorticoid
      responsive element within it plays a substantial role in the expression of
      aromatase P450.

PMID- 12050212
TI  - Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical
      hypothyroidism.
AB  - Germline loss-of-function mutations of TSH receptor (TSHR) gene have been
      described in families with partial or complete TSH resistance. Large TSH
      elevations were generally found in the patients with homozygous or compound
      heterozygous mutations. In this study, we sequenced the entire TSHR gene in a
      series of 10 unrelated patients with slight (6.6-14.9 mU/liter) to moderate (24
      46 mU/liter) elevations of serum TSH, associated with definitely normal free
      thyroid hormone concentrations. Thyroid volume was normal in all patients, except
      two with a modest hypoplasia. Autoimmune thyroid disease was excluded in all
      patients on the basis of clinical and biochemical parameters. Eight patients had
      at least one first-degree relative bearing the same biochemical picture. TSHR
      mutations were detected in 4 of 10 cases by analyzing DNA from peripheral
      leukocytes. A compound heterozygosity (P162A on maternal allele, and the novel
      mutation C600R on the paternal one) was found in the patient with the highest TSH
      levels. Only one TSHR allele was mutated in the remaining three cases, and no
      alterations in TSHR gene promoter were detected in all of these probands. A novel
      mutation (L467P) was detected on the maternal allele in one patient and in her
      monozygotic twin. Previously described inactive mutants, T655Delta and C41S, were
      detected in the other two cases. When tested on several occasions, circulating
      TSH values fluctuating above the upper limit of the normal range could be shown
      in heterozygous subjects of these families. A dominant mode of inheritance of the
      biochemical alterations was detected in these cases. Mutant TSHRs were studied
      during transient expression in COS7 and HEK293T cells. Their TSH-independent cAMP
      accumulation activities were very low or similar to mock-transfected cells, and
      no increases were seen after maximal hormone stimulation. Flow cytometry
      experiments showed a poor level of expression of all mutant TSHRs at the cell
      membrane. In conclusion, we found several loss-of-function mutations of TSHR,
      including two novel ones, in a series of unrelated patients with slightly
      elevated TSH levels. Therefore, partial resistance to TSH action is a frequent
      finding among patients with slight hyperthyrotropinemia of nonautoimmune origin.
      Germline mutations of TSHR may be associated with serum TSH values fluctuating
      above the upper limit of the normal range, also in the heterozygous state.

PMID- 12050213
TI  - A novel nonstop mutation in the stop codon and a novel missense mutation in the
      type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing,
      respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal
      hyperplasia.
AB  - We investigated two novel point mutations in the human type II 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) gene causing a mild and a severe form of
      3beta-HSD deficiency congenital adrenal hyperplasia. The first is a nonstop
      mutation in the normal stop codon 373 of the gene in exon IV [TGA (Stop) --> TGC
      (Cys) = Stop373C) identified from one allele of a female child with premature
      pubarche whose second allele had an E142K mutation. The Stop373C mutation
      predictably results in an open reading frame and a mutant-type (MT) II 3beta-HSD
      protein containing 467 amino acid residues, compared with the 372 amino acid
      residues of wild-type (WT) protein. The second is a homozygous missense mutation
      in codon 222 [CCA (Pro) --> ACT (Thr) = P222T] in the gene identified from a
      female neonate with salt-wasting disorder. The pcDNA vectors containing the
      constructs of WT II 3beta-HSD cDNA, WT cDNA with the open reading frame (WT
      cDNA(+)), MT Stop373C with the open reading frame (Stop373C(+)) and MT P222T cDNA
      were transfected in COS-I and 293T cells and expressed a similar amount of 3beta
      HSD mRNA. The enzyme activity in intact cells using pregnenolone and
      dehydroepiandrosterone as substrate in the medium (1 micromol/liter) was
      identical between the WT cDNA and the WT cDNA(+), but was decreased to 27% of the
      WT enzymes at 6 h by MT Stop373C(+) enzyme, and was undetectable by P222T enzyme.
      In the homogenates of the cells, both MT Stop373C(+) and P222T enzyme activities
      and enzymes were undetectable despite clear detection of WT enzyme activities and
      WT enzymes. LH response to an LHRH analog stimulation in the pubertal female with
      the Stop373C/E142K genotypes and in a pubertal female with compound 273/318
      frameshift genotypes were comparable to and higher than control females,
      respectively. In conclusion, a structurally lengthy MT II 3beta-HSD enzyme due to
      a nonstop mutation was relatively detrimental in intact cells causing the
      nonclassic phenotype of 3beta-HSD deficiency. A missense P222T mutation was
      seriously detrimental, causing the classic phenotype of 3beta-HSD deficiency. The
      undetectable Stop373C and P222T enzymes on Western blottings, together with the
      respective in vivo and in vitro data, suggest that a relative instability of
      Stop373C enzyme and a profound instability of the P222T enzyme are likely the
      detrimental molecular mechanisms. The increased LH in the female with the
      frameshift genotype and the appropriate LH response in the female with the
      nonstop genotype correlated with predictably severe and mild ovarian type II
      3beta-HSD deficiency, respectively.

PMID- 12050214
TI  - A polymorphism within the vitamin D-binding protein gene is associated with
      Graves' disease but not with Hashimoto's thyroiditis.
AB  - Graves' disease and Hashimoto's thyroiditis are common autoimmune thyroid
      disorders. Experimentally, 1,25(OH)(2) D(3) prevents Hashimoto's thyroiditis.
      Vitamin D serum levels in Graves' disease were found to be significantly lower
      than in nonautoimmune hyperthyroidism. The polymorphic vitamin D-binding protein
      (DBP) greatly facilitates vitamin D actions, and DBP alleles differ regarding
      their affinity for 1,25(OH)(2) D(3). Therefore, we investigated polymorphisms of
      the DBP gene for an association with thyroid autoimmunity. Families with an
      offspring affected by Graves' disease (95 pedigrees) or by Hashimoto's
      thyroiditis (92 pedigrees) encompassing 561 individuals of Caucasian origin were
      genotyped for three DBP polymorphisms [(TAAA)(N) in intron 8; StyI; and HaeIII in
      exon 11]. Indirect haplotyping and (extended) transmission disequilibrium testing
      were performed. There was a significant transmission disequilibrium of the intron
      8 polymorphism in patients with Graves' disease (P < 0.03) but not of the exon 11
      polymorphism. In contrast, neither the intron 8 nor the exon 11 polymorphism was
      associated with Hashimoto's thyroiditis. Maternal and paternal transmission as
      well as allele frequencies in DQ2(+) and DQ2(-) patients did not differ in either
      disease. Therefore, allelic variants of the DBP gene confer susceptibility to
      Graves' disease but not to Hashimoto's thyroiditis in our population. These
      findings support a role of the vitamin D endocrine system in thyroid
      autoimmunity.

PMID- 12050215
TI  - AIRE mutations and human leukocyte antigen genotypes as determinants of the
      autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, OMIM
      240300) is a rare autoimmune disease caused by mutations in the autoimmune
      regulator (AIRE) gene on chromosome 21q22.3. This monogenic disease provides an
      interesting model for studies of other common and more complex autoimmune
      diseases. The most common components of APECED are chronic mucocutaneous
      candidiasis, hypoparathyroidism, and Addison's disease, but several other
      endocrine deficiencies and ectodermal dystrophies also occur and the phenotype
      varies widely. The AIRE genotype also varies; 42 different mutations have been
      reported so far. To understand the complexity of the phenotype, we studied the
      AIRE and human leukocyte antigen (HLA) class II genotypes in a series of patients
      with APECED. The only association between the phenotype and the AIRE genotype was
      the higher prevalence of candidiasis in the patients with the most common
      mutation, R257X, than in those with other mutations. Addison's disease was
      associated with HLA-DRB1*03 (P = 0.021), alopecia with HLA-DRB1*04- DQB1*0302 (P
      < 0.001), whereas type 1 diabetes correlated negatively with HLA-DRB1*15
      DQB1*0602 (P = 0.036). The same HLA associations have previously been established
      for non-APECED patients. We conclude that mutation of AIRE per se has little
      influence on the APECED phenotype, whereas, in contrast to earlier reports, HLA
      class II is a significant determinant.

PMID- 12050216
TI  - Expression and function of vasoactive intestinal peptide, pituitary adenylate
      cyclase-activating polypeptide, and their receptors in the human adrenal gland.
AB  - VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) are two
      regulatory peptides that possess remarkable amino acid sequence homology and act
      through common receptors, named PAC(1), VPAC(1), and VPAC(2). PAC(1) receptor is
      selective for PACAP, whereas VPAC(1) and VPAC(2) receptors bind both VIP and
      PACAP. We have investigated the expression and function of VIP, PACAP, and their
      receptors in the zona glomerulosa (ZG), zonae fasciculata and reticularis, and
      adrenal medulla (AM) of the human adrenal cortex. RT-PCR and RIA detected VIP and
      PACAP expression exclusively in AM cells. RT-PCR demonstrated the presence of
      PAC(1) mRNA only in AM and of VPAC(1) and VPAC(2) mRNAs in both ZG and AM cells.
      VIP and PACAP concentration-dependently increased aldosterone and catecholamine
      secretion from cultured ZG and AM cells. The catecholamine response to both
      peptides was higher than the aldosterone response, and the secretagogue action of
      PACAP was more intense than that of VIP. The aldosterone response of cultured ZG
      cells to VIP or PACAP was unaffected by the PAC(1) receptor antagonist PACAP-(6
      38) (PAC(1)-A), but was significantly decreased by the VPAC(1) receptor
      antagonist [Ac-His(1),D-Phe(2),Lys(15),Arg(16)]VIP-(3-7),GH-releasing factor-(8
      27)-NH(2) (VPAC(1)-A). The catecholamine response of cultured AM cells to VIP was
      lowered by VPAC(1)-A and unaffected by PAC(1)-A; conversely, the catecholamine
      response to PACAP was reduced by both PAC(1)-A and VPAC(1)-A. Simultaneous
      exposure to both antagonists did not abolish the catecholamine response to PACAP.
      Collectively, our findings allow us to conclude that in human adrenals 1) VIP and
      PACAP biosynthesis exclusively occurs in AM cells; 2) ZG cells are provided with
      functional VPAC(1) and VPAC(2) receptors, whose activation by VIP or PACAP
      elicits a moderate aldosterone response; 3) AM cells possess PAC(1), VPAC(1), and
      VPAC(2) receptors, whose activation evokes a marked catecholamine response; and
      4) the catecholamine response to PACAP is more intense than that to VIP, because
      it is mediated by all subtypes of VIP/PACAP receptors.

PMID- 12050218
TI  - Regulated expression of signal transducer and activator of transcription, Stat5,
      and its enhancement of PRL expression in human endometrial stromal cells in
      vitro.
AB  - Differentiation of human endometrium during the secretory phase of the menstrual
      cycle is characterized by expression of a variety of genes implicated in the
      establishment and maintenance of pregnancy. An increased abundance of signal
      transducers and activators of transcription (Stats) in the secretory phase
      suggests Stat5 as a component of the differentiation of endometrium in response
      to ovarian hormone stimulation in vivo. Decidualization is initiated in a subset
      of endometrial stromal cells (ESC) in vivo during the secretory phase, but it is
      unclear whether regulated expression of Stat5 is a feature of these cells. Here,
      therefore, the abundance and subcellular distribution of Stat5 in ESC after a
      decidualization stimulus of cAMP plus medroxyprogesterone acetate (MPA) has been
      investigated in vitro. Western blotting revealed an increase in the apparent
      abundance of Stat5a and Stat5b, in the cytosolic and nuclear fractions, at 2, 3,
      and 4 d after stimulation. The potential functional relevance of this increase in
      Stat5 is suggested by the ability of transiently transfected Stat5a or Stat5b to
      significantly enhance the response of the decidual PRL promoter to cAMP/MPA and
      attenuation of the response to cAMP/MPA by dominant negative Stat5. Recent
      evidence suggests endometrial differentiation, including PRL production, as a
      possible target of antiphospholipid antibodies (aPL) prevalent in recurrent
      miscarriage. Monoclonal antibody, ID2, which has similar reactivity as human aPL,
      significantly decreased the apparent abundance of nuclear Stat5b in response to
      cAMP/MPA and was associated with decreased decidual PRL promoter activation and
      PRL secretion. Regulated expression of Stat5 is therefore a component of decidual
      differentiation of human ESC and contributes significantly to activation of the
      decidual PRL promoter. Alteration of this process by an aPL component suggests
      decidual differentiation as a potential clinical target in recurrent early
      miscarriages.

PMID- 12050219
TI  - Identification of three novel mutations in the KAL1 gene in patients with
      Kallmann syndrome.
AB  - Kallmann's syndrome (KS) is characterized by the association of hypogonadotropic
      hypogonadism and anosmia or hyposmia. Genetic defects have been observed
      throughout the KAL1 gene, located on the Xp22.3 region, in less than 50% of the
      patients. We report the molecular study of the KAL1 gene in 12 males with KS. PCR
      of the 14 exons of the KAL1 gene was performed on genomic DNA. PCR products of
      all exons were purified and sequenced. Three novel genetic defects were found.
      One patient exhibited a complete deletion of exon 5. The second presented a
      duplication of nucleotides 158-168; this insertion causes a termination codon
      (TGA) within the same exon. The third presented a mutation in exon 6, in which
      codon 262 changes from arginine to a stop codon. In the remaining nine
      individuals, no mutations were found. Three previously reported polymorphic
      changes were also documented. The deletion of exon 5 occurs within the region
      encoding the first fibronectin type III-like repeat of the KAL1 protein, this
      being the first KS patient who exhibits a complete deletion of a single exon of
      the KAL1 gene. The duplication of nucleotides in exon 1 is located in the
      conserved cysteine-rich N-terminal region that corresponds to the whey acidic
      protein motif, affecting the KAL1 protein either by interrupting the normal
      transcription or stopping the translation at the stop codon. The last novel
      mutation, a stop codon in exon 6, is located within the region encoding the first
      fibronectin type III-like repeat of the KAL1 protein. The absence of mutations in
      the majority of patients suggests the possibility of the existence of other genes
      involved or that in certain individuals the presence of various polymorphisms
      within the KAL1 gene could predispose to disease, as has been demonstrated in
      other pathological entities.

PMID- 12050220
TI  - Remission of Graves' hyperthyroidism and A/G polymorphism at position 49 in exon
      1 of cytotoxic T lymphocyte-associated molecule-4 gene.
AB  - We studied whether a patient with Graves' disease will go into remission during
      antithyroid drug (ATD) treatment. Remission of Graves' hyperthyroidism is
      predicted by a smooth decrease in TSH receptor antibody (TRAb) during ATD
      treatment. Cytotoxic T cell lymphocyte-associated molecule-4 (CTLA-4) may play an
      important role in the development of Graves' hyperthyroidism and in its
      remission. We studied A/G polymorphism at position 49 in exon 1 of the CTLA-4
      gene in 144 Japanese Graves' patients. We intended to reveal the possible
      association of CTLA-4 gene polymorphism with the remission of Graves'
      hyperthyroidism. All patients with Graves' disease were treated with ATD. Thyroid
      stimulating antibody and TSH binding inhibitory Ig were measured as TRAb. We
      analyzed CTLA-4 genotypes and alleles with PCR. We calculated the frequencies of
      CTLA-4 genotypes and alleles. A significant increase in the frequency of the G
      allele was seen in Graves' patients compared with controls (P = 0.0095). Graves'
      patients were divided into three groups (A, B, and C) according to time of TRAb
      disappearance after the start of ATD treatment. In group A patients TRAb had
      disappeared within 1 yr after the start of ATD treatment, in group B TRAb had
      disappeared between the beginning of the second year and the end of the fifth
      year of treatment, and in group C TRAb continued to be positive after 5 yr of ATD
      treatment. The frequencies of the GG genotype and the G allele were significantly
      higher in group C patients with persistently positive TRAb over 5 yr of ATD
      treatment than in the other groups (P < 0.0001). Group C patients did not have
      the AA genotype. The periods of time until remission were significantly shorter
      in the AA genotype. Graves' patients with the G allele need to continue ATD
      treatment for longer periods.

PMID- 12050221
TI  - Relation between disease phenotype and HLA-DQ genotype in diabetic patients
      diagnosed in early adulthood.
AB  - We investigated inaugural disease phenotype in relation to the presence or
      absence of diabetes-associated autoantibodies and human leukocyte antigen (HLA)
      DQ risk genotypes in adult-onset diabetic patients. Blood samples and
      questionnaires were obtained from 1584 recent-onset Belgian Caucasian patients
      (age 15-39 yr at diagnosis of primary diabetes) who were recruited by the Belgian
      Diabetes Registry over an 11-yr period. At clinical diagnosis, antibody-positive
      patients (n = 1198) were on average younger and had more symptoms, a more acute
      disease onset, lower body mass index, and random C-peptide levels, but higher
      insulin needs, glycemia, and prevalence of ketonuria, HLA-DQ, and 5' insulin gene
      susceptibility genotypes (P < 0.001 vs. antibody-negative patients; n = 386). In
      antibody-positive patients, these characteristics did not differ according to HLA
      DQ genotype. However, in antibody-negative subjects, we found that patients were
      younger (P = 0.001); had a lower body mass index (P < 0.001), higher insulin
      needs (P = 0.014), and amylasemia (P = 0.001); and tended to have a higher
      glycemia and lower C-peptide in the presence of susceptible HLA-DQ genotypes.
      Differences according to HLA-DQ genotype subsisted after careful age-matching. In
      conclusion, we found no relation between initial disease phenotype and HLA-DQ
      genotype in antibody-positive diabetic young adults. In contrast, antibody
      negative patients displayed more type 1-like features when carrying susceptible
      HLA-DQ genotypes known to promote the development of antibody-positive diabetes.
      The overrepresentation of these susceptibility genotypes in antibody-negative
      patients suggests the existence of an immune-mediated disease process with as yet
      unidentified immune markers in a subgroup of seronegative patients.

PMID- 12050223
TI  - Variation within the type 2 diabetes susceptibility gene calpain-10 and
      polycystic ovary syndrome.
AB  - Variation within the calpain-10 gene (CAPN10) has been proposed to account for
      linkage to type 2 diabetes on chromosome 2q in Mexican-Americans, and
      associations with diabetes have been reported in several other populations. Given
      the epidemiological, physiological, and genetic overlap between type 2 diabetes
      and polycystic ovary syndrome (PCOS), CAPN10 represents a strong candidate gene
      for a role in PCOS susceptibility. Using both family based and case-control
      association resources (146 parent-offspring trios; 185 additional PCOS cases; 525
      control subjects, all of European ancestry), we sought association between CAPN10
      variation and PCOS, focusing on four single nucleotide polymorphism (SNP)
      variants (SNP-44, SNP-43; SNP-19; SNP-63). On single-locus transmission
      disequilibrium analysis in the 146 trios, there was nominal evidence (P = 0.03)
      of excess transmission of the more common allele at SNP-63. This association was
      not, however, replicated in the case-control analysis. No other significant
      associations were observed at the single-locus or haplotype level in either the
      transmission-disequilibrium or case-control analyses. The relative risk for the
      high-risk diabetes susceptibility 112/121 genotype (SNPs 43-19-63) was 0.84 (95%
      confidence intervals, 0.40-1.71). No associations were seen with intermediate
      traits of relevance to diabetes and PCOS pathogenesis. We have found no evidence
      from these analyses that CAPN10 gene variation influences susceptibility to PCOS.

PMID- 12050224
TI  - Newly proposed hormonal criteria via genotypic proof for type II 3beta
      hydroxysteroid dehydrogenase deficiency.
AB  - To define the hormonal criteria via genotypic proof for 3beta-hydroxysteroid
      dehydrogenase (3beta-HSD) deficiency in the adrenals and gonads, we investigated
      the type II 3beta-HSD genotype in 55 patients with clinical and/or hormonal
      presentation suggesting compromised adrenal with or without gonadal 3beta-HSD
      activity. Fourteen patients (11 males and 3 females) had ambiguous genitalia with
      or without salt wasting and with or without premature pubarche. One female
      neonate had salt wasting only. Twenty-five children (4 males and 21 females) had
      premature pubarche only. Fifteen adolescent and adult females had hirsutism with
      or without menstrual disorder. The type II 3beta-HSD gene, including the promoter
      region up to -1053 base, all exons I, II, III, IV, and exon and intron
      boundaries, was sequenced in all subjects. Eight patients had a proven or
      predictably deleterious mutation in both alleles of the type II 3beta-HSD gene,
      and 47 patients had no apparent mutation in the gene. ACTH-stimulated (1 h post
      iv bolus of 250 microg Cortrosyn) serum 17-hydroxypregnenolone (Delta5-17P)
      levels and basal and ACTH-stimulated ratios of Delta5-17P to cortisol (F) in the
      genotypic proven patients were unequivocally higher than those of age-matched or
      pubic hair stage matched genotype-normal patients or control subjects (n = 7-30
      for each group). All other baseline and ACTH-stimulated hormone parameters,
      including dehydroepiandrosterone (DHEA) levels, ratios of Delta5-17P to 17-OHP
      and DHEA to androstenedione in the genotype-proven patients, overlapped with the
      genotype-normal patients or control subjects. The hormonal findings in the
      genotype-proven patients suggest that the following hormonal criteria are
      compatible with 3beta-HSD deficiency congenital adrenal hyperplasia (numeric and
      graphic reference standards from infancy to adulthood are provided): ACTH
      stimulated Delta5-17P levels in 1) neonatal infants with ambiguous genitalia at
      or greater than 378 nmol/liter equivalent to or greater than 5.3 SD above the
      control mean level [95 +/- 53 (SD) nmol/liter]; 2) Tanner I children with
      ambiguous genitalia at or greater than 165 nmol/liter equivalent to or greater
      than 35 SD above the control mean level [12 +/- 4.3 (SD) nmol/liter]; 3) children
      with premature pubarche at or greater than 294 nmol/liter equivalent to or
      greater than 54 SD above Tanner II pubic hair stage matched control mean level
      [17 +/- 5 (SD) nmol/liter]; and 4) adults with at or greater than 289 nmol/liter
      equivalent to or greater than 21 SD above the normal mean level [25 +/- 12 (SD)
      nmol/liter]. ACTH-stimulated ratio of Delta5-17P to F in 1) neonatal infants at
      or greater than 434 equivalent to or greater than 6.4 SD above the control mean
      ratio [88 +/- 54 (SD)]; 2) Tanner I children at or greater than 216 equivalent to
      or greater than 23 SD above the control mean ratio [12 +/- 9 (SD)]; 3) children
      with premature pubarche at or greater than 363 equivalent to or greater than 38
      SD above the control mean ratio [20 +/- 9 (SD)]; and 4) adults at or greater than
      4010 equivalent to or greater than 221 SD above the normal mean ratio [29 +/- 18
      (SD)]. Conversely, the hormonal data in the genotype-normal patients suggest the
      following hormonal criteria are not consistent with 3beta-HSD deficiency
      congenital adrenal hyperplasia: ACTH-stimulated Delta5-17P levels in children
      with premature pubarche up to 72 nmol/liter equivalent to up to 11 SD above the
      control mean level, and in hirsute females up to 150 nmol/liter equivalent to up
      to 12 SD above the normal female mean level [28 +/- 10 (SD) nmol/liter]; and ACTH
      stimulated Delta5-17P to F ratio in children with premature pubarche up to 67
      equivalent to up to 5 SD above the control mean ratio, and in hirsute females up
      to 151 equivalent to up to 10 SD above the normal mean ratio [32 +/- 12 (SD)].
      These findings help define newly proposed hormonal criteria to accurately predict
      inherited 3beta-HSD deficiency.

PMID- 12050225
TI  - An androgen receptor gene mutation (E653K) in a family with congenital adrenal
      hyperplasia due to steroid 21-hydroxylase deficiency as well as in partial
      androgen insensitivity.
AB  - An androgen receptor (AR) variant (E653K) was found in two unrelated Swedish
      families. One family had two girls affected with congenital adrenal hyperplasia
      (CAH) due to steroid 21-hydroxylase deficiency. The girls, who showed mild
      virilization in relation to their CYP21 genotype, had inherited the AR gene
      mutation from their father, who showed no symptoms of androgen insensitivity. The
      other family had a boy with partial androgen insensitivity and ambiguous
      genitalia, and he had inherited the AR gene mutation from his mother. The mutant
      receptor showed a transactivating capacity in the same range as the normal
      receptor at high concentrations of ligand (1 and 10 nM dihydrotestosterone), but
      absent or reduced transactivation at low levels (0.01 and 0.1 nM). The receptor
      variant was not found among 250 additional unselected Swedish men. Sequencing of
      the AR gene in five unrelated CAH girls with the I172N mutation in CYP21 and
      minimal virilization did not reveal any additional deviations from the normal
      reference sequence. In addition, there was no difference in lengths of the
      polymorphic CAG repeat in the AR gene between CAH girls with the I172N mutation
      who showed minimal and severe virilization, and we found no evidence of skewed X
      inactivation. We conclude that AR gene mutations or polymorphisms are not a
      common factor influencing the degree of hyperandrogenic symptoms displayed by CAH
      girls, and that the AR E653K mutation is compatible with normal genital
      development, although it can cause genital malformations in susceptible
      individuals.

PMID- 12050227
TI  - Phospholipase A(2) and cyclooxygenase gene expression in human preimplantation
      embryos.
AB  - Phospholipase A(2) (PLA(2)) and cyclooxygenase (COX) are two key enzymes in PG
      synthesis; the latter has two forms, COX-1 and COX-2. mRNA was extracted from
      single preimplantation embryos and examined for PLA(2), COX-1, and COX-2 gene
      expression by RT-PCR to investigate whether PLA(2) and COX genes are expressed in
      human preimplantation conceptuses from zygote to blastocyst stage and to compare
      COX-1 and COX-2 gene expression within the same stage of embryonic development.
      Expression of PLA(2), COX-1, and COX-2 was detected in 48, 37, and 45%,
      respectively, of total embryos examined. COX-1 was expressed in approximately 66%
      of early human preimplantation embryos from zygote to two-cell stage, whereas COX
      2 was expressed in about 58% of later stage embryos from eight-cell to blastocyst
      stage (P < 0.05). Furthermore, COX-2 mRNA and protein were localized to
      trophectoderm in blastocyst stage embryos. In conclusion, PLA(2), COX-1, and COX
      2 are expressed during early human embryonic development and may contribute to
      the production of PGs such as PGE(2) in human embryogenesis. COX-1 and COX-2 are
      differentially expressed, with COX-2 being primarily expressed by trophectoderm
      in late-stage human preimplantation embryos, which may promote embryonic
      differentiation and implantation.

PMID- 12050228
TI  - Expression of phosphorylated p27(Kip1) protein and Jun activation domain-binding
      protein 1 in human pituitary tumors.
AB  - The cyclin-dependent kinase inhibitor p27(Kip1) (p27) plays a pivotal role in
      controlling cell proliferation during development and tumorigenesis. p27 has been
      implicated in pituitary tumorigenesis in studies of knockout mice and in analyses
      of human pituitary tumor samples. In this study, we further explored the role of
      p27 in human pituitary tumors by measuring levels of phosphorylated p27 (P-p27),
      and also Jun activation domain-binding protein 1 (Jab1), which is thought to
      facilitate the phosphorylation and degradation of p27, in normal pituitary tissue
      (n = 21), pituitary adenomas (n = 75), and pituitary carcinomas (n = 10). The
      amount of p27 protein in corticotroph adenomas and pituitary carcinomas was much
      lower than that in normal pituitary tissue or other types of pituitary adenoma.
      Nuclear P-p27 protein levels were significantly decreased in the adenomas,
      compared with the normals, and were much lower in the carcinomas, compared with
      either normal pituitary tissue or pituitary adenomas. However, P-p27 levels in
      corticotroph adenomas were similar to normal pituitary tissue, thus demonstrating
      a greatly increased ratio of P-p27 to p27 specifically in corticotroph tumors. No
      difference was found in Jab1 protein levels in either corticotroph tumors or
      other pituitary adenomas, compared with normal tissue, but there was a small but
      significant increase in Jab1 levels in carcinomas. Corticotroph and metastatic
      tumors both showed a significantly higher Ki-67 labeling index than normal
      pituitary or other types of pituitary adenomas, and in general the Ki-67 labeling
      index was negatively correlated with p27 nuclear staining. The amount of p27 and
      Jab1 mRNA was positively correlated in all pituitary samples studied but did not
      correlate with the changes in immunostaining. Our findings suggest that in
      corticotroph tumors there is an accentuated phosphorylation of p27 into P-p27,
      possibly related to increased cyclin E expression, whereas both p27 and P-p27 are
      subject to increased degradation in pituitary carcinomas. Such variations in
      phosphorylation may play a role in pituitary tumorigenesis, but modulation of
      Jab1 is unlikely to be important in the pathogenesis of pituitary adenomas.

PMID- 12050229
TI  - Localization of the activin signal transduction components in normal human
      ovarian follicles: implications for autocrine and paracrine signaling in the
      ovary.
AB  - The intraovarian function of gonadally produced activin is unclear, and many in
      vitro studies have suggested a role for activin in follicle development. To
      identify the follicular developmental stages at which these ligands may be
      acting, we have used immunohistochemical localization of the ligand subunits,
      receptor subtypes, and Smad co-activating proteins within the same follicles. The
      earliest stages of follicle development (primordial to primary) show no
      immunoreactivity for the activin subunits or their receptors. Oocytes from these
      early stages contain immunostaining for Smad2 and Smad4, consistent with
      signaling by other TGF-beta superfamily members. Immunostaining for the activin
      type II receptor first appears in oocytes and oocyte-associated cumulus cells at
      the secondary follicle stage. However, activin is not produced in these
      follicles, suggesting that either the receptors are inactive at this stage or
      they are used by another protein. Co-localization of activin and inhibin
      subunits, receptors, and Smads only occurs in granulosa and theca cells of small
      antral, aromatase-positive follicles as well as granulosa cells of early atretic
      follicles. In addition, multivariate statistical analysis reveals that the
      ligands and their cellular signaling complexes are independently regulated.
      Together, these data strongly suggest that the intraovarian role of activin is
      limited to a few developmental stages and that other TGF-beta family members may
      use this cell autonomous signaling machinery in early follicle development.

PMID- 12050230
TI  - A novel, C-terminal dominant negative mutation of the GR causes familial
      glucocorticoid resistance through abnormal interactions with p160 steroid
      receptor coactivators.
AB  - Primary cortisol resistance is a rare, inherited or sporadic form of generalized
      end-organ insensitivity to glucocorticoids. Here, we report a kindred in which
      affected members had a heterozygous T to G base substitution at nucleotide 2373
      of exon 9alpha of the GR gene, causing substitution of Ile by Met at position
      747. This mutation was located close to helix 12, at the C terminus of the ligand
      binding domain, which has a pivotal role in the formation of activation function
      (AF)-2, a subdomain that interacts with p160 coactivators. The affinity of the
      mutant GR for dexamethasone was decreased by about 2-fold, and its
      transcriptional activity on the glucocorticoid-responsive mouse mammary tumor
      virus promoter was compromised by 20- to 30-fold. In addition, the mutant GR
      functioned as a dominant negative inhibitor of wild-type receptor-induced
      transactivation. The mutant GR through its intact AF-1 domain bound to a p160
      coactivator, but failed to do so through its AF-2 domain. Overexpression of a
      p160 coactivator restored the transcriptional activity and reversed the negative
      transdominant activity of the mutant GR. Interestingly, green fluorescent protein
      (GFP)-fused GRalphaI747M had a slight delay in its translocation from the
      cytoplasm into the nucleus and formed coarser nuclear speckles than GFP-fused
      wild-type GRalpha. Similarly, a GFP-fused p160 coactivator had a distinctly
      different distribution in the nucleus in the presence of mutant vs. wild-type
      receptor, presenting also as coarser speckling. We conclude that the mutation at
      amino acid 747 of the GR causes familial, autosomal dominant glucocorticoid
      resistance by decreasing ligand binding affinity and transcriptional activity,
      and by exerting a negative transdominant effect on the wild-type receptor. The
      mutant receptor has an ineffective AF-2 domain, which leads to an abnormal
      interaction with p160 coactivators and a distinct nuclear distribution of both.

PMID- 12050231
TI  - Genetic analysis of Japanese patients with 21-hydroxylase deficiency:
      identification of a patient with a new mutation of a homozygous deletion of
      adenine at codon 246 and patients without demonstrable mutations within the
      structural gene for CYP21.
AB  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is one of the
      most common inherited metabolic diseases. We studied 52 Japanese 21-hydroxylase
      deficiency patients corresponding to 49 families (98 chromosomes) to detect the
      mutations in 21-hydroxylase genes using Southern blotting, PCR-restriction
      fragment length polymorphism, and a direct sequencing method. Among the 52
      patients (49 families), 35 patients (33 families) were diagnosed as the salt
      wasting type, 12 (12 families) as the simple virilizing type, and 5 (4 families)
      as the nonclassical type. Our findings were as follows. 1) The complete genotype
      that had homozygous or compound heterozygous mutations was determined in 43 of 49
      families (87.8%). Among the remaining patients, no mutation was found in the
      structural gene of either allele in 3 cases, and a mutation was detected in only
      1 allele in 3 cases. This means that at least 9 of 98 alleles have some unusual
      mutations or recombinations that we cannot detect by our method or gene defects
      outside of the structural gene. 2) Although the common mutation of Caucasian
      nonclassical patients is V281L, none of our 4 nonclassical families showed this
      mutation, and 3 of them had the P30L mutation at least on 1 allele. 3) We
      identified a putative new mutation, homozygous deletion of adenine at codon 246,
      in a salt-wasting patient. Although we have not analyzed the functional
      consequence of this mutation, it causes substitution noncoding for Met(256) in
      exon 7 and premature termination of the mRNA before the heme-binding region of
      the P450 polypeptide, which would result in a completely nonfunctional enzyme.

PMID- 12050232
TI  - HOXA11 silencing and endogenous HOXA11 antisense ribonucleic acid in the uterine
      endometrium.
AB  - Hoxa11 is an essential regulator of embryonic uterine development and the cyclic
      development of the adult uterine endometrium. Hoxa11 is required for female
      fertility, as evidenced by targeted mutation. Here we demonstrate a naturally
      occurring Hoxa11 (mouse)/HOXA11 (human) antisense transcript present in the adult
      mouse and human endometrium. HOXA11 antisense transcript levels varied during the
      menstrual cycle, with peak antisense RNA levels occurring in the midproliferative
      phase, varying inversely with mRNA expression levels. HOXA11 protein levels
      correlated temporally with peak mRNA levels. In primary stromal cell culture,
      progesterone down-regulated HOXA11 antisense transcription, and this was followed
      by up-regulation of HOXA11 mRNA, suggesting a possible role for the antisense
      transcript in regulating mRNA expression. Attempts to block Hoxa11 function by
      transfection of the murine uterus with Hoxa11 antisense oligonucleotides failed
      to interrupt normal uterine function, suggesting that Hoxa11 antisense does not
      regulate Hoxa11 mRNA by formulation of sense/antisense duplexes. We propose that
      HOXA11 antisense functions by transcriptional interference, repressing HOXA11
      expression by competing for transcription of the common gene, rather than by
      sense/antisense interaction.

PMID- 12050233
TI  - A family of autosomal dominant hypocalcemia with a positive correlation between
      serum calcium and magnesium: identification of a novel gain of function mutation
      (Ser(820)Phe) in the calcium-sensing receptor.
AB  - To date about 20 activating mutations in the calcium-sensing receptor (CaR) gene
      have been identified to cause autosomal dominant hypocalcemia (ADH) or sporadic
      hypoparathyroidism. We report a novel activating mutation in the CaR gene in a
      Japanese family with ADH. The proband, a 15-yr-old boy, and 5 other patients in 3
      generations were asymptomatic, except for the proband's grandmother who had a
      history of seizures. They showed mild hypocalcemia (1.68-1.98 mmol/liter) with
      normal urinary calcium excretion and low normal serum PTH levels. Their serum
      magnesium concentrations were below normal in 3 adults and within the normal
      range in 3 teenagers. There was a significant positive correlation (r = 0.90; P <
      0.05) between the serum calcium and magnesium concentrations of 6 affected
      members. Nucleotide sequencing revealed that the proband had a known polymorphism
      (Gly(990)Arg) and a novel heterozygous mutation substituting phenylalanine for
      serine at codon 820 (Ser(820)Phe) in the sixth transmembrane helix of the CaR. In
      other family members, the Ser(820)Phe mutation cosegregated with hypocalcemia.
      The mutation was not detected in 50 control subjects. The Gly(990)Arg
      polymorphism was observed in 8 of 9 family members with or without hypocalcemia
      and in 36 of 50 controls. The sensitivity of the Ser(820)Phe mutant CaR to
      calcium was assessed using transiently transfected HEK293 cells and measuring the
      increases in intracellular Ca(2+) concentrations in response to the changes in
      extracellular Ca(2+). The concentration-response curve of the mutant receptor was
      left-shifted, and its EC(50) (2.5 mM) was significantly (P < 0.05) lower than
      that of the wild-type CaR (3.3 mM). We conclude that the Ser(820)Phe mutation in
      the CaR caused ADH in this family. The positive correlation between serum calcium
      and magnesium levels observed in this family may support the concept that renal
      CaR acts as a magnesium sensor as well as a calcium sensor.

PMID- 12050235
TI  - Frequent occurrence of an intron 4 mutation in multiple endocrine neoplasia type
      1.
AB  - MEN1 is an autosomal dominant disorder characterized by parathyroid, pituitary,
      and pancreatic tumors. The MEN1 gene is located on chromosome 11q13 and encodes a
      610-amino acid protein. MEN1 mutations are of diverse types and are scattered
      throughout the coding region, such that almost every MEN1 family will have its
      individual mutation. To further characterize such mutations we ascertained 34
      unrelated MEN1 probands and undertook DNA sequence analysis. This identified 17
      different mutations in 24 probands (2 nonsense, 2 missense, 2 in-frame deletions,
      5 frameshift deletions, 1 frameshift deletional-insertion, 3 frameshift
      insertions, 1 donor splice site mutation, and a g-->a transition that resulted in
      a novel acceptor splice site in intron 4). The intron 4 mutation was found in 7
      unrelated families, and the tumors in these families varied considerably,
      indicating a lack of genotype-phenotype correlation. However, this intron 4
      mutation is the most frequently occurring germline MEN1 mutation ( approximately
      10% of all mutations), and together with 5 others at codons 83-84, 118-119, 209
      211, 418, and 516, accounts for 36.6% of all mutations, a finding that indicates
      an approach for identifying the widely diverse MEN1 mutations.

PMID- 12050236
TI  - Two novel aquaporin-2 mutations responsible for congenital nephrogenic diabetes
      insipidus in Chinese families.
AB  - Mutations in the aquaporin-2 gene (AQP2), encoding the vasopressin-regulated
      water channel of the renal collecting duct, are responsible for the autosomal
      recessive or dominant forms of congenital nephrogenic diabetes insipidus. We
      describe two new families with normal hypotensive and coagulation responses
      following the administration of desamino-8-D-arginine AVP, a clinical suggestion
      of normal vasopressin-2 receptors. The patients were compound heterozygotes for
      point mutations at nucleotide position 170 (CAG to CCG; Q57P) and at position 299
      (GGA to GTA; G100V) in exon 1 of the AQP2 gene. Expression of the G57P and G100V
      AQP2 proteins in Xenopus oocytes showed only 1.3-fold and 1.2-fold increase,
      respectively, in the water permeability in contrast to 8.0-fold increase in
      oocytes injected with wild-type cRNA. Immunoblots of oocyte lysate revealed the
      intensities of the 29-kDa bands were comparable among oocytes injected with wild
      type and mutant cRNAs. Immunocytochemistry showed the plasma membrane was not
      stained in oocytes injected with cRNA of Q57P and of G100V. These results provide
      evidence that the Q57P and G100V mutations in congenital nephrogenic diabetes
      insipidus are attributable to the misrouting of AQP2.

PMID- 12050237
TI  - Expression of the mRNA coding for 11beta-hydroxysteroid dehydrogenase type 1 in
      adipose tissue from obese patients: an in situ hybridization study.
AB  - Glucocorticoids play an important role in determining adipose tissue metabolism
      and distribution. Patients with Cushing's syndrome or receiving corticosteroid
      therapy develop a reversible visceral obesity. In obese patients, although
      circulating concentrations of cortisol are not consistently elevated, local
      conversion of inactive cortisone to active cortisol in adipose tissue, catalyzed
      by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), could amplify
      glucocorticoid signaling. We have studied, using semiquantitative in situ
      hybridization, 11beta-HSD-1 mRNA expression in the adipocyte and stromal
      compartments of sc abdominal adipose tissue obtained from 12 lean patients and sc
      abdominal and visceral adipose tissue obtained from 18 obese patients. 11beta-HSD
      1 mRNA was expressed in adipocytes, stroma, and walls of vessels. Localization of
      11beta-HSD-1 mRNA did not differ between lean sc and obese sc or visceral adipose
      tissue. 11beta-HSD-1 mRNA levels were significantly (P = 0.0106) increased in the
      adipocyte compartment of sc adipose tissue obtained from obese patients as
      compared with nonobese ones, whereas no significant change (P = 0.446) was found
      in the stromal compartment. In obese patients, 11beta-HSD-1 mRNA expression was
      increased (P = 0.0157) in the stromal compartment of visceral compared with sc
      tissue, whereas no significant change (P = 0.8767) was found in the adipocyte
      compartment. In summary, our data show that 11beta-HSD-1 mRNA is increased in
      adipose tissue from obese patients, in the abdominal sc fat in adipocytes and in
      the visceral fat in both adipocytes and stroma. This observation suggests that an
      overexpression of 11beta-HSD-1 may explain part of the glucocorticoid-induced
      metabolic disorders linked to obesity and may promote visceral fat deposition.

PMID- 12050238
TI  - ERbeta1 and the ERbeta2 splice variant (ERbetacx/beta2) are expressed in distinct
      cell populations in the adult human testis.
AB  - Estrogens can regulate germ cell function. Estrogen action is mediated via high
      affinity ERs; two subtypes (ERalpha and ERbeta) have been identified. We have
      shown previously that ERbeta is expressed in nuclei of multiple human testicular
      cells. A variant isoform of human (h) ERbeta (hERbetacx/2), formed by alternative
      splicing, has been identified in testicular cDNA libraries by two laboratories.
      The present study examined the expression of wild-type (ERbeta1) and variant
      (ERbeta2) beta receptors in human testes by 1) RT-PCR with isoform specific
      primers, and 2) single and double immunohistochemistry using monoclonal
      antibodies raised against peptides unique to the C termini of hERbeta1 and
      hERbeta2. PCR products specific for ERbeta1 and ERbeta2 were amplified from cDNA
      pools prepared from human testes and granulosa cells. On Western blots, the anti
      ERbeta1 monoclonal antibody bound to recombinant ERbeta1 and the anti-ERbeta2
      monoclonal to recombinant hERbeta2. Neither bound to the other ERbeta isoform nor
      to recombinant ERalpha. ERbeta1 and ERbeta2 proteins were both detected in human
      testis. Immunoexpression of ERbeta1 was most intense in pachytene spermatocytes
      and round spermatids, whereas low levels of expression were detected in Sertoli
      cells, spermatogonia, preleptotene, leptotene, zygotene, and diplotene
      spermatocytes. Highest levels of expression of ERbeta2 protein were detected in
      Sertoli cells and spermatogonia with low/variable expression in preleptotene,
      pachytene, and diplotene spermatocytes. No immunostaining was detected in
      elongating spermatids. Most interstitial cells expressed more ERbeta2 than
      ERbeta1. It is speculated that the cells most susceptible to modulation by
      estrogenic ligands are round spermatids in which levels of expression of ERbeta1
      are high. In contrast, expression of ERbeta2, an isoform that may act as a
      dominant negative inhibitor of ER action, in Sertoli cells and spermatogonia,
      could protect these cells from adverse effects of estrogens.

PMID- 12050239
TI  - Ghrelin gene: identification of missense variants and a frameshift mutation in
      extremely obese children and adolescents and healthy normal weight students.
AB  - Ghrelin induces obesity via central and peripheral mechanisms. Administration of
      ghrelin leads to increased food intake and decreased fat utilisation in rodents.
      Ghrelin levels are decreased in obese individuals. Recently, a polymorphism (Arg
      51-Gln) within the ghrelin gene (GHRL) was described to be associated with
      obesity. We screened the GHRL coding region in 215 extremely obese German
      Children and adolescents (study group 1) and 93 normal weight students (study
      group 2) by single strand conformation polymorphism analysis (SSCP). We found the
      two previously described single nucleotide polymorphisms (SNP: Arg-51-Gln and Leu
      72-Met) in similar frequencies in study groups 1 and 2 (allele frequencies were:
      0.019 and 0.016 for the 51-Gln allele and 0.091 and 0.086 for the 72-Met allele,
      respectively). Hence, we could not confirm the previous finding. Additionally,
      two novel variants were identified within the coding region: (1) We detected one
      healthy normal weight individual with a frameshift mutation (2bp deletion at
      codon 34). This frameshift mutation affects the coding region of the mature
      ghrelin. Hence, it is highly likely that the normal weight student is haplo
      insufficient for ghrelin. (2) An A to T transversion leads to an amino acid
      exchange from Gln to Leu at amino acid position 90. The frequency of the 90-Leu
      allele was significantly higher in the extremely obese children and adolescents
      (0.063) than in the normal weight students (0.016; nominal p = 0.011).
      Additionally, we genotyped 134 underweight students and 44 normal weight adults
      for this SNP. Genotype frequencies were similar in extremely obese children and
      adolescents, underweight students and normal weight adults (p > 0.8). In
      conclusion, we identified four sequence variants in the coding region of the
      ghrelin gene in individuals belonging to different weight extremes. A frameshift
      mutation was detected in a normal weight individual. None of the variants seem to
      influence weight regulation.

PMID- 12050240
TI  - Polymorphism in the IGF-I gene: clinical relevance for short children born small
      for gestational age (SGA).
AB  - Low birth weight is associated with an increased risk in adult life of type 2
      diabetes, hypertension and cardiovascular disease (CVD). The fetal insulin
      hypothesis postulates that genes involving insulin resistance could effect birth
      weight and disease in later life (Hattersley, 1999). Besides insulin, there is
      extensive evidence that insulin-like growth factor-I and -II (IGF-I, IGF-II) play
      an important role in fetal growth. We hypothesized that minor genetic variation
      in the IGF-I gene could influence pre- and postnatal growth. Three microsatellite
      markers located in the IGF-I gene in 124 short children (height < -1.88 SDS) who
      were born small for gestational age (SGA) and their parents were studied. SGA was
      defined as both a birth weight and birth length below -1.88 SDS for gestational
      age. Two polymorphic markers showed transmission disequilibrium. Allele 191 of
      the IGF1.PCR1 marker was transmitted more frequently from parent to child (chi(2)
      = 4.8 and p = 0.02) and allele 198 of the 737/738 marker was transmitted less
      frequently from parent to child (chi(2)= 4.5 and p = 0.03). Children carrying the
      191-allele had significantly lower IGF-1 levels than children not carrying this
      allele (-1.1 SDS vs. -0.05 SDS; p = 0.03). Also, head circumference SDS remained
      smaller in children with allele 191 compared to children without allele 191 (-2.1
      SDS vs. -0.9 SDS; p = 0.003). Our results show that genetically determined low
      IGF-I levels may lead to a reduction in birth weight, length and head
      circumference and to persistent short stature and small head circumference in
      later life (proportionate small). Since low IGF-I levels are associated with type
      2 diabetes and CVD, we propose that the IGF-I gene may provide a link between low
      birth weight and such diseases in later life.

PMID- 12050241
TI  - Gender-specific responses of lean body composition and non-gender-specific
      cardiac function improvement after GH replacement in GH-deficient adults.
AB  - GH deficiency (GHD) in adulthood is accompanied by physical and psychological
      impairments. One hundred fifteen patients (67 male, 48 female) with pronounced
      GHD were enrolled in a randomized, double-blind, placebo-controlled study with
      objectives that included effects on body composition, cardiac structure, and
      function and safety of replacement therapy with recombinant human GH (Saizen).
      Sixty patients (31 male, 29 female) received GH at a dose of 0.005-0.010 mg/kg.d,
      and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of
      body composition by dual-energy x-ray absorptiometry demonstrated a treatment
      difference in lean body mass increase of 2.1 kg (between-group comparison, P <
      0.0001), which was significantly greater among males than females (P < 0.0001)
      [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females:
      GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0-6
      months (95% confidence limits)] and was associated with IGF-I changes. The
      decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by
      DEXA was also evident from bioelectric impedance and anthropometric measurements.
      Echocardiography showed comparable improvement in left ventricular systolic
      function after GH treatment in both genders. End-systolic volume decreased by 4.3
      +/- 10.5 ml (from 35.8 +/- 17.6 ml; between-group comparison, P = 0.035) and
      ejection fraction increased by 5.1 +/- 10.0% (from 55.0 +/- 11.2%; between-group
      comparison, P = 0.048), approaching normalcy. Diastolic function did not change
      as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow
      secondary to atrial contraction, or ratio of peak mitral early diastolic and
      atrial contraction velocity. GH treatment was well tolerated, with adverse events
      primarily related to effects on fluid balance. No apparent relationship between
      IGF-I levels and the occurrence or severity of adverse events was identified. In
      conclusion, GH replacement therapy in adults with GHD demonstrated beneficial
      effects on lean body mass composition that was more pronounced in males than
      females. In contrast, cardiac function improvement appears to benefit both
      genders equally.

PMID- 12050242
TI  - Longitudinal study of serum placental GH in 455 normal pregnancies: correlation
      to gestational age, fetal gender, and weight.
AB  - Placental GH is thought to be responsible for the rise in maternal IGF-I during
      pregnancy and is considered to be important for fetal growth. In this prospective
      longitudinal study of healthy pregnant women, we investigated determinants of
      placental GH in maternal serum. Serum was obtained from 455 women with normal
      singleton pregnancies at approximately 19 and 28 wk gestation. Serum placental GH
      concentrations were measured by a highly specific immunoradiometric assay, and
      fetal size was measured by ultrasound. Data on birth weight, gender, prepregnancy
      body mass index (BMI), parity, and smoking habits were obtained from medical
      records. Serum placental GH concentrations were detectable in serum from all
      women as early as 14 wk gestation and increased during pregnancy in all
      individuals (P < 0.001). Placental GH levels at second examination were found to
      be higher in women carrying female fetuses [median, 9.0 ng/ml; 95% confidence
      interval (CI), 4.7-23.0] compared with women carrying male fetuses (median, 8.2
      ng/ml; 95% CI, 3.96-19.4; P = 0.004). Similarly, the increase in placental GH
      between 19 and 28 wk gestation was significantly larger in female fetus bearers
      than in male fetus bearers (P = 0.002). Placental GH at second examination was
      positively correlated with gestational age (P = 0.002) and negatively correlated
      with prepregnancy BMI (P = 0.039). Placental GH correlated with fetal weight at
      approximately 28 wk gestation (P = 0.002) but did not predict birth weight at
      term. Our study supports the role of maternal placental GH in the regulation of
      fetal growth. In conclusion, we found that 1) placental GH levels correlated
      significantly with fetal size at 28 wk gestation; 2) GH levels were measurable in
      serum from all women as early as 14 wk gestation; 3) maternal prepregnancy BMI
      and smoking were determinants of placental GH levels, although their specific
      effects on the serum maternal levels of placental GH remain to be seen; and 4)
      women carrying female fetuses have significantly higher placental GH levels
      compared with women carrying male fetuses at 28 wk gestation.

PMID- 12050243
TI  - GHRH plus arginine in the diagnosis of acquired GH deficiency of childhood-onset.
AB  - We evaluated the GH-releasing effect of GHRH plus arginine (ARG) in 36 patients
      (22 males and 14 females) with acquired GH deficiency including idiopathic
      inflammatory pituitary stalk thickness (n = 15), Langerhans cell histiocytosis
      (LCH) affecting the hypothalamic-pituitary area (n = 11), and craniopharyngioma
      (n = 10). All of the patients (mean age, 9.6 +/- 3.1 yr; range, 5.6-20.8) showed
      GH response less than 10 microg/liter after 2 pharmacological stimuli and were
      tested with GHRH plus ARG at a mean age of 11.2 +/- 4.1 yr. Twenty-nine patients
      had vasopressin deficiency, 10 had TSH deficiency, 8 had gonadotropin deficiency,
      and 4 had ACTH deficiency. The median peak GH response to insulin test was 2.1
      microg/liter (range, 1.1-2.9), whereas it was 1.5 microg/liter (range, 1.3-2.4)
      after ARG. The median peak GH response to insulin was significantly lower in the
      patients with craniopharyngioma (1.4 microg/liter; range, 0.8-1.7) than in the
      patients with idiopathic pituitary stalk thickness (2.2 microg/liter; range, 1.0
      2.4) or with LCH (2.6 microg/liter; range 2.0-4.3, P = 0.02). The median peak GH
      response to ARG was significantly lower in the patients with idiopathic
      inflammatory pituitary stalk thickness (1.3 microg/liter; range, 0.8-1.8) than in
      those with craniopharyngioma (1.5 microg/liter; range, 1.1-1.6) or with LCH (2.8
      microg/liter; range, 1.9-3.2, P = 0.00007). The median peak GH response after
      GHRH plus ARG was significantly lower in the overall patient population (8.3
      microg/liter; range, 4.4-28.4) than in the age-matched controls (49.8
      microg/liter; range, 39.9-81.6, P < 0.00001). The median peak GH response was
      significantly lower in the patients with craniopharyngioma (4.6 microg/liter;
      range, 3.6-6.3) than in those with LCH (8.9 microg/liter; range, 4.4-28.4) or
      with idiopathic pituitary stalk thickness (12.6 microg/liter, range, 6.4-24, P =
      0.07). Ten patients had a GH response of more than 20 microg/liter after GHRH
      plus ARG. There was a trend toward a decrease in peak GH response to GHRH plus
      ARG (r = -0.57, P = 0.06) as patient age increased. For cut-off values of 20
      microg/liter, the sensitivity of GHRH plus ARG was 75% (95% CI, 57.8-87.9%) and
      the specificity was 96.4% (95% CI, 89.9-99.2%); whereas, for cut-off values of
      24.2 microg/liter, sensitivity was 86.1% (95% CI, 70.5-95.3%), and specificity
      was 95.2% (95% CI, 88.2-98.7%). The median IGF-I level did not differ between the
      children with idiopathic pituitary stalk thickness (57 microg/liter; range, 46
      68), those with LCH (55 microg/liter; range, 34-63), and those with
      craniopharyngioma (41 microg/liter; range, 39-49). The present study confirmed
      the diagnostic potential of the GHRH-plus-ARG test in children with acquired GH
      deficiency caused by hypothalamic-pituitary lesion. It stimulates GH secretion to
      a greater extent in those patients with GH deficiency with primary involvement of
      the hypothalamic area, e.g. patients with idiopathic pituitary stalk thickness or
      LCH, than in those with both hypothalamic and pituitary lesion, as in
      craniopharyngioma. In some patients, the GHRH-plus-ARG test stimulates GH
      response to a so-called: normal value, suggesting that pituitary responsiveness
      to GHRH plus ARG may fail to recognize acquired GHD. Finally, the number of
      pituitary hormone deficits and the patient's age affect the GH response to GHRH
      plus ARG.

PMID- 12050244
TI  - Glucocorticoid replacement in pituitary surgery: guidelines for perioperative
      assessment and management.
AB  - Patients undergoing surgical resection of pituitary adenomas are frequently given
      perioperative glucocorticoid therapy. There are no randomized controlled studies
      assessing the need for such steroids; however, several studies have documented
      changes in the hypothalamic-pituitary-adrenal (HPA) axis associated with
      pituitary surgery. Based on the evidence available, this article details
      recommendations for the perioperative management of glucocorticoid therapy in
      patients with pituitary tumors. For patients with proven ACTH deficiency
      preoperatively [usually based on response to a short ACTH 1-24 (Synacthen) test],
      48 hours of supraphysiological glucocorticoid therapy should be administered
      perioperatively (e.g. hydrocortisone, 50 mg every 8 hours on day 0, 25 mg every 8
      hours on day 1, and 25 mg at 0800 h on day 2). For patients with intact HPA
      function preoperatively, and in whom selective adenomectomy is possible,
      perioperative glucocorticoids are not necessary. Early postoperative assessment
      depends on daily clinical assessment of the patient and 0800 h plasma cortisol
      levels. Cortisol levels over 450 nM (16 microg/dl) reflect normal HPA function,
      and levels less than 100 nM (3.6 microg/dl) are consistent with ACTH deficiency.
      Cortisol levels between 100 and 250 nM (3.6-9 microg/dl) may be ACTH deficient
      and should receive morning hydrocortisone replacement until definitive HPA axis
      testing. Cortisol levels between 250 and 450 nM (9-16 microg/dl) are unlikely to
      be ACTH deficient but should receive additional steroids for stress until a
      definitive test is performed. For those requiring definitive testing, the insulin
      tolerance test, the overnight metyrapone test, or the glucagon stimulation test
      are appropriate and may be performed as early as d 7-10 or, if more convenient,
      wk 4-6. Following the guidelines suggested here should reduce the use of
      unnecessary glucocorticoids, while ensuring the safety of patients is not
      compromised.

PMID- 12050245
TI  - GH treatment in adults with chronic liver disease: a randomized, double-blind,
      placebo-controlled, cross-over study.
AB  - Patients with chronic liver disease (CLD) are catabolic and GH-resistant. The
      effects of supraphysiological recombinant human GH (rhGH; 0.2 IU.kg(-1).d(-1))
      treatment in adults with CLD were assessed in a randomized, double-blind, placebo
      controlled cross-over trial (4-wk dietary run-in, 4-wk treatment, and 2-wk wash
      out phases). Nine adults with mild- to moderate-severity CLD participated (median
      age, 49 yr; three males and six females; Child's classification A in six and B in
      three). Biopsy-proven etiologies were: alcohol (four patients), primary biliary
      cirrhosis (three patients), non-A, non-B, non-C hepatitis (one patient), and
      cryptogenic (one patient). Treatment with rhGH increased serum IGF-I (median
      increase over placebo, +93 microg.liter(-1); P = 0.004), IGF-binding protein-3
      (+0.9 mg.liter(-1): P = 0.004), and acid labile subunit (+10.7 nM; P = 0.004).
      Total body potassium (+8.0 g; P = 0.023), body weight (+1.6 kg; P = 0.008), and
      total body water (by bioelectrical impedance; +4.9 kg; P = 0.004) increased.
      Resting metabolic rate (+313 ml.kg(-1).min(-1); P = 0.004) and lipid oxidation
      (+1072.0 kcal.d(-1); P = 0.032) increased. Metabolic changes included increased
      fasting plasma glucose (+1.2 mM; P = 0.008), insulin (+33.8 mU.liter(-1); P =
      0.004), C-peptide (+0.7 nM; P = 0.004), and free-fatty acids (+0.1 mEq.liter(-1);
      P = 0.04). Clinical side effects included worsening edema and ascites.
      Hepatocellular function did not change. Therefore, rhGH treatment in CLD: 1)
      overcame hepatic GH resistance; 2) may have improved whole-body protein
      catabolism; 3) increased lipolysis and lipid oxidation; 4) increased insulin
      resistance; and 5) had potent antinatriuretic effects. Long-term safety and
      efficacy require further assessment.

PMID- 12050246
TI  - Effects of 12 months of GH treatment on cortical and trabecular bone content of
      IGFs and OPG in adults with acquired GH deficiency: a double-blind, randomized,
      placebo-controlled study.
AB  - To investigate the effects of 12 months of GH treatment on cortical and
      trabecular bone content of IGFs, iliac crest bone biopsies were obtained from 25
      patients with GH deficiency (9 women and 16 men; ages, 21-61 yr; mean, 46 yr) who
      were randomized to sc injections with GH (2 IU/m(2).d) or placebo for 12 months.
      Levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, osteocalcin,
      OPG, RANKL, and total protein were determined in extracts obtained after EDTA and
      guanidine hydrochloride extraction. Calcium was determined after HCl hydrolysis.
      Comparing changes during GH or placebo treatment, significant increases were
      observed during GH substitution for cortical and trabecular bone content of IGF-I
      [mean difference vs. placebo (mean +/- SEM), 97 +/- 30 and 72 +/- 38%] and OPG
      (mean difference vs. placebo, 109 +/- 59 and 51 +/- 19%). Also, a significant
      decline was found for cortical osteocalcin (mean difference vs. placebo, -49 +/-
      22%) during GH treatment. In conclusion, our results indicate that long-term GH
      treatment increases the accumulation of IGF-I and OPG in cortical and trabecular
      bone in patients with GH deficiency, and this may in turn lead to an increase in
      bone mass and improved skeletal biomechanical competence.

PMID- 12050247
TI  - Decreased plasma adiponectin concentrations in women with dyslipidemia.
AB  - Adiponectin, the gene product of the adipose most abundant gene transcript 1, is
      a novel adipocyte-derived peptide that has been considered to have
      antiinflammatory and antiatherogenic effects. To characterize the relationship
      between adiponectin and lipids metabolism, we measured fasting plasma adiponectin
      concentration by ELISA, serum total cholesterol, high-density lipoprotein
      cholesterol (HDL-C), triglyceride (TG), and apolipoprotein (apo) levels in 352
      nondiabetic women, 16-86 yr old, with a wide range of body weight [body mass
      index (BMI), 14.8-36.3 kg/m(2)]. Plasma adiponectin concentrations in women with
      the highest tertile of TG (1.69 mM < or approximately) were decreased, compared
      with the middle (1.13 < or = approximately < 1.69) or lowest tertile of TG
      (approximately < 1.13) (5.9 +/- 0.5 vs. 7.5 +/- 0.3, 9.2 +/- 0.2 microg/ml; P <
      0.005, 0.001). Plasma adiponectin with the lowest tertile of HDL-C (approximately
      < 1.16 mM) was decreased, compared with the middle (1.16 < or = approximately <
      1.81) or highest tertile of HDL-C (1.81 < or approximately ) (5.7 +/- 0.5 vs. 7.8
      +/- 0.2, 10.1 +/- 0.4 microg/ml; both P < 0.001). These relationships had similar
      tendencies after adjustment for BMI, body fat mass, age, or diastolic blood
      pressure. Adiponectin was negatively correlated with serum TG (r = -0.33, P <
      0.0001), atherogenic index [(total cholesterol - HDL-C)/HDL-C] (r = -0.34, P <
      0.0001), apo B (r = -0.45, P < 0.0001), or apo E (r = -0.29, P < 0.05), and
      positively correlated with serum HDL-C (r = 0.39, P < 0.0001) or apo A-I levels
      (r = 0.42, P < 0.002). Those negative relationships became stronger after
      adjusting for BMI or body fat mass. The slightly positive correlation between
      adiponectin and age, blood urea nitrogen, or creatinine levels was also observed
      (all P < 0.001). These results indicate that high-TGnemia and low-HDL-Cnemia are
      associated with low plasma adiponectin concentrations in nondiabetic women.
      Further efforts must now be targeted to determine whether adiponectin causes
      these lipid abnormalities and thus whether it is partly responsible for the
      atherogenic risk seen in the metabolic syndrome.

PMID- 12050248
TI  - Androgens and bone density in women with hypopituitarism.
AB  - Hypopituitarism is associated with osteopenia and a reduction in lean body mass.
      We have recently demonstrated markedly reduced serum androgen levels in women
      with hypopituitarism. We hypothesized that serum androgen levels and lean body
      mass are important determinants of bone mineral density (BMD) in women with
      hypopituitarism. In addition, because IGF-I may stimulate androgen secretion in
      women, we investigated whether GH administration results in an increase in serum
      androgen levels. Sixteen women with a history of pituitary disease of adult-onset
      and serum GH levels less than 5 ng/ml on stimulation testing underwent BMD and
      body composition testing by dual-energy x-ray absorptiometry. Univariate
      regression analysis revealed strong correlations between androgen levels and BMD
      [lateral spine BMD and dehydroepiandrosterone sulfate (DHEAS) (r = 0.68, P =
      0.03), total hip BMD and free T (r = 0.60, P = 0.01), Ward's triangle BMD and
      DHEAS (r = 0.68, P = 0.004), Ward's triangle BMD and free T (r = 0.54, P = 0.03),
      femoral neck BMD and free T (r = 0.52, P = 0.04), and femoral neck BMD and DHEAS
      (r = 0.51, P = 0.04)]. When adjusted for age using Z scores, correlations at the
      femoral neck no longer reach significance. Correlations between androgens and BMD
      at other sites, including anterior-posterior spine and total body, were not
      significant, and neither total T nor androstenedione correlated with BMD at any
      site. Lean body mass strongly correlated with BMD [total hip (r = 0.80, P =
      0.0002), total body (r = 0.78, P = 0.0003), trochanter (r = 0.74, P = 0.001),
      Ward's triangle (r = 0.56, P = 0.02), femoral neck (r = 0.53, P = 0.04), and
      anterior-posterior spine (r = 0.52, P = 0.04)]. In stepwise regression models,
      DHEAS determined 47% of the variation in Ward's triangle BMD (R(2) = 0.47, P =
      0.004) and 46% of lateral spine BMD (R(2) = 0.46, P = 0.03). Lean body mass
      determined 64% of the variation in total hip BMD (R(2) = 0.64, P = 0.0002), 62%
      of total body (R(2) = 0.62, P = 0.0003), and 55% of trochanter BMD (R(2) = 0.55,
      P = 0.001). Subjects were then randomized to receive GH at a dose of 12.5
      microg/kg per day or placebo for 12 months in a double-blind protocol. Serum
      androgen levels were obtained at baseline, 1, 3, 6, 9, and 12 months after
      initiation of GH. Androgen levels did not increase in the women receiving GH for
      12 months, compared with those receiving placebo. Stimulation of androgen
      secretion is therefore unlikely to be a mechanism underlying the improvement in
      BMD, body composition, or quality of life observed with GH administration. In
      conclusion, androgen levels and lean body mass may be important determinants of
      BMD in women with hypopituitarism. It remains to be determined whether androgen
      replacement therapy itself or an increase in lean body mass achieved as a result
      of androgen administration will result in an improvement in BMD in this
      population.

PMID- 12050250
TI  - Bone density and amenorrhea in ballet dancers are related to a decreased resting
      metabolic rate and lower leptin levels.
AB  - Osteopenia, which is correlated with amenorrhea and poor nutritional habits, has
      been well documented in elite ballet dancers. Estrogen replacement therapy and
      recovery from amenorrhea have not been associated with normalization of bone
      density. Thus, the osteopenia may be related to changes brought about by chronic
      dieting or other factors, such as a hypometabolic state induced by poor
      nutrition. The purpose of this study was to investigate the relationship of
      chronic dieting and resting metabolic rate (RMR) to amenorrhea and bone density.
      RMR, bone density, eating disorder assessments, leptin levels, and complete
      menstrual and medical histories were determined in 21 elite ballet dancers and in
      27 nondancers (age, 20-30 yr). No significant correlations were found between
      high EAT26 scores, a measure of disordered eating, and RMR, bone densities, body
      weight, body fat, or fat-free mass. However, when RMR was adjusted for fat-free
      mass (FFM), a significant positive correlation was found between RMR/FFM and bone
      density in both the arms (P < 0.001) and spine (P < 0.05) in ballet dancers, but
      not in the normal controls. The dancers also demonstrated significantly higher
      EAT scores (22.9 +/- 10.3 vs. 4.1 +/- 2.4; P < 0.001) and lower RMR/FFM ratios
      (30.0 +/- 2.2 vs. 32.05 +/- 2.8; P < 0.01). The only variable to predict lower
      RMR/FFM in the entire sample was ever having had amenorrhea; this group had
      significantly higher EAT scores (18.0 +/- 13.5 vs. 10.3 +/- 10.2; P < 0.05),
      lower leptin levels (4.03 +/- 0.625 vs. 7.10 +/- 4.052; P < 0.05), and lower bone
      mineral density in the spine (0.984 +/- 0.11 vs. 1.10 +/- 0.13; P < 0.05) and arm
      (0.773 +/- 0.99 vs. 0.818 +/- 0.01; P < 0.05). We hypothesize that the
      correlation between low RMR and lower leptin levels and bone density may be more
      strongly related to nutritional habits in ballet dancers, causing significant
      depression of RMR, particularly for those with a history of amenorrhea.

PMID- 12050252
TI  - Alendronate increases bone mass and reduces bone markers in postmenopausal
      African-American women.
AB  - Previous studies indicated that aminobisphosphonate alendronate sodium, a potent
      inhibitor of bone resorption, increases bone mineral density (BMD) at the hip and
      spine, reduces markers of bone turnover, and reduces the risk of fractures in
      Caucasian postmenopausal women. The purpose of the present study was to
      investigate whether alendronate increases BMD and reduces markers of bone
      turnover in African-American postmenopausal women. In a multicenter, randomized,
      double-blind, placebo-controlled study, 65 African-American women, aged 45 to 88
      yr, were randomly assigned to either placebo (n = 33) or alendronate 10 mg daily
      (n = 32) for 2 yr. Mean BMD T scores of the lumbar spine at baseline were -3.18
      in the placebo-treated group and -3.09 in the alendronate-treated group. All
      women took 500 mg elemental calcium daily in the form of calcium carbonate and
      500 IU vitamin D. Alendronate significantly increased BMD and reduced markers of
      bone formation and resorption, compared with placebo. At 2 yr, mean changes +/-
      SE in BMD were 6.5% +/- 0.7% for the lumbar spine (P < 0.001), 4.5% +/- 1.0% for
      the femoral neck (P < 0.001), 6.4% +/- 0.6% for the femoral trochanter (P <
      0.001), 4.1% +/- 0.7% for the total hip (P < 0.001), 0.7% +/- 0.5% for the one
      third forearm (NS), and 2.0% +/- 0.4% for the total body (P < 0.001) in women
      treated with alendronate, compared with 0.9% +/- 0.6% (NS), 0.5% +/- 1.1% (NS), 
      0.2 +/- 0.8 (NS), -1.1 +/- 0.7% (NS), -0.8% +/- 0.6% (NS), and -1.2% +/- 0.6% (P
      < 0.05) for the lumbar spine, femoral neck, trochanter, total hip, one third
      forearm, and total body, respectively, in women treated with placebo. At 2 yr,
      mean serum bone-specific alkaline phosphatase had declined by 46.3% with
      alendronate (P < 0.001) and 13.6% with placebo (P < 0.01), and mean urinary N
      telopeptide of type I collagen/creatinine ratio had declined by 70.5% with
      alendronate (P < 0.001) and 6.7% with placebo (NS). The incidence of adverse
      experiences was not different between the two groups. We conclude that in
      postmenopausal African-American women with osteoporosis, alendronate, 10 mg daily
      for 2 yr, increases BMD at the lumbar spine, hip, and total body and reduces
      markers of bone remodeling and is well tolerated.

PMID- 12050251
TI  - Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in
      type 2 diabetic patients.
AB  - We examined the effect of pioglitazone on abdominal fat distribution to elucidate
      the mechanisms via which pioglitazone improves insulin resistance in patients
      with type 2 diabetes mellitus. Thirteen type 2 diabetic patients (nine men and
      four women; age, 52 +/- 3 yr; body mass index, 29.0 +/- 1.1 kg/m(2)), who were
      being treated with a stable dose of sulfonylurea (n = 7) or with diet alone (n =
      6), received pioglitazone (45 mg/d) for 16 wk. Before and after pioglitazone
      treatment, subjects underwent a 75-g oral glucose tolerance test (OGTT) and two
      step euglycemic insulin clamp (insulin infusion rates, 40 and 160 mU/m(2).min)
      with [(3)H]glucose. Abdominal fat distribution was evaluated using magnetic
      resonance imaging at L4-5. After 16 wk of pioglitazone treatment, fasting plasma
      glucose (179 +/- 10 to 140 +/- 10 mg/dl; P < 0.01), mean plasma glucose during
      OGTT (295 +/- 13 to 233 +/- 14 mg/dl; P < 0.01), and hemoglobin A(1c) (8.6 +/-
      0.4% to 7.2 +/- 0.5%; P < 0.01) decreased without a change in fasting or post
      OGTT insulin levels. Fasting plasma FFA (674 +/- 38 to 569 +/- 31 microEq/liter;
      P < 0.05) and mean plasma FFA (539 +/- 20 to 396 +/- 29 microEq/liter; P < 0.01)
      during OGTT decreased after pioglitazone. In the postabsorptive state, hepatic
      insulin resistance [basal endogenous glucose production (EGP) x basal plasma
      insulin concentration] decreased from 41 +/- 7 to 25 +/- 3 mg/kg fat-free mass
      (FFM).min x microU/ml; P < 0.05) and suppression of EGP during the first insulin
      clamp step (1.1 +/- 0.1 to 0.6 +/- 0.2 mg/kg FFM.min; P < 0.05) improved after
      pioglitazone treatment. The total body glucose MCR during the first and second
      insulin clamp steps increased after pioglitazone treatment [first MCR, 3.5 +/-
      0.5 to 4.4 +/- 0.4 ml/kg FFM.min (P < 0.05); second MCR, 8.7 +/- 1.0 to 11.3 +/-
      1.1 ml/kg FFM(.)min (P < 0.01)]. The improvement in hepatic and peripheral tissue
      insulin sensitivity occurred despite increases in body weight (82 +/- 4 to 85 +/-
      4 kg; P < 0.05) and fat mass (27 +/- 2 to 30 +/- 3 kg; P < 0.05). After
      pioglitazone treatment, sc fat area at L4-5 (301 +/- 44 to 342 +/- 44 cm(2); P <
      0.01) increased, whereas visceral fat area at L4-5 (144 +/- 13 to 131 +/- 16
      cm(2); P < 0.05) and the ratio of visceral to sc fat (0.59 +/- 0.08 to 0.44 +/-
      0.06; P < 0.01) decreased. In the postabsorptive state hepatic insulin resistance
      (basal EGP x basal immunoreactive insulin) correlated positively with visceral
      fat area (r = 0.55; P < 0.01). The glucose MCRs during the first (r = -0.45; P <
      0.05) and second (r = -0.44; P < 0.05) insulin clamp steps were negatively
      correlated with the visceral fat area. These results demonstrate that a shift of
      fat distribution from visceral to sc adipose depots after pioglitazone treatment
      is associated with improvements in hepatic and peripheral tissue sensitivity to
      insulin.

PMID- 12050255
TI  - Recurrent iodine deficiency in Tasmania, Australia: a salutary lesson in
      sustainable iodine prophylaxis and its monitoring.
AB  - Even mild iodine deficiency during early childhood and pregnancy has the
      potential to impair neurological development. Often considered a problem of
      developing nations, a number of industrialized countries are at risk of
      deficiency. Despite past success with intentional and unintentional iodine
      fortification, recurrence of deficiency is an ever-present risk. Tasmania, an
      island state of the Commonwealth of Australia, has a history of endemic iodine
      deficiency, which was successfully eliminated by iodine prophylaxis initiated in
      1950. In this report we describe a formal assessment of iodine nutrition in the
      Tasmanian population, 50 yr after initiation of the prophylaxis program. The
      requirements and obstacles to achieving sustainable iodine prophylaxis in an
      otherwise affluent community are considered. A cross-sectional study was
      undertaken during the yr 2000. Urinary iodine excretion (UIE) and thyroid
      ultrasonography were assessed in a representative statewide sample of school-age
      children. Children (n = 225) aged 4 to 17 yr from throughout Tasmania were
      studied. The sample comprised 99 girls and 126 boys. The median UIE was 84
      microg/liter (87 microg/liter for males and 81 microg/liter for females), with
      UIE 50 microg/liter or less in 20%. Based on age-specific World Health
      Organization/International Council for the Control of Iodine Deficiency Disorders
      normative data for thyroid volume, the prevalence of elevated thyroid volume was
      5.3% for boys and 3.5% for girls. However, after correcting the World Health
      Organization/International Council for the Control of Iodine Deficiency Disorders
      reference data, the prevalence increased to 24.6% for boys and 20.7% for girls.
      No significant difference in the thyroid volumes was found between males and
      females in this study. These data confirm the recurrence of mild iodine
      deficiency in Tasmania. The failure of sustained iodine prophylaxis highlights
      the universal importance of persistent surveillance, use of sustainable measures,
      public awareness, and a specific legislative framework for managing ongoing
      iodine prophylaxis. Our findings also emphasize the importance of accurate
      reference data for assessment thyroid volume.

PMID- 12050253
TI  - Marked disproportionality in bone size and mineral, and distinct abnormalities in
      bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional
      study.
AB  - Most women with Turner syndrome (TS) have no gonadal activity and thus lack
      estrogen. Bone mineral density (BMD) is often reduced, leading to an increased
      risk of osteoporosis and fractures. However, growth retardation with reduced
      final height and other endocrine disturbances may compromise interpretation of
      skeletal measurements. The aim of the present study was to explore skeletal
      findings, bone metabolism, and calcium homeostasis in TS. Sixty women with TS
      (age, 37 +/- 9 yr) and 181 normal age-matched female controls were studied. Bone
      area (A; square centimeters), bone mineral content (BMC; grams), area-adjusted
      BMD (aBMD; grams/square centimeter), and volumetric BMD (vBMD; grams/cubic
      centimeter) were measured at lumbar spine, femoral neck, and forearm using dual
      energy x-ray absorptiometry. Twenty-eight percent had osteopenia, and 23% had
      osteoporosis, according to World Health Organization criteria. At the lumbar
      spine, A, BMC, aBMD, and vBMD were reduced by 18, 27, 11, and 6%, respectively;
      at the femoral neck, A, BMC, and aBMD were reduced by 2, 10, and 8%,
      respectively, whereas the 9% reduction in vBMD was insignificant (P = 0.07); and
      in the forearm, A, BMC, and aBMD were reduced by 53, 55, and 9%, respectively.
      Bone markers indicated an enhanced bone resorption (21 and 23% increase in C
      terminal and N-terminal cross-linking telopeptides of type I collagen/creatinine,
      respectively) with unchanged (osteocalcin, procollagen I N-terminal propeptide)
      or reduced (54% reduction in bone alkaline phosphatase) bone formation. Plasma
      levels of calcium and 25-hydroxyvitamin D (26%) were reduced, and PTH levels
      increased (74%) in TS. IGF-I (30%), IGF binding protein 3 (18%), testosterone
      (50%), and SHBG (40%) were reduced in TS. In summary, A, BMC, and aBMD were found
      to be universally reduced in TS, whereas vBMD was slightly reduced in the spine.
      Increased resorption of bone was present, with normal or blunted bone formation,
      suggesting uncoupling or imbalance in bone remodeling. Skeletal changes may be
      induced by chromosome abnormalities or by secondary endocrine or metabolic
      changes related to a relative estrogen deficiency, testosterone deficiency,
      reduced IGF-I, low vitamin D status, and secondary hyperparathyroidism.

PMID- 12050257
TI  - Novel mutations in CYP21 detected in individuals with hyperandrogenism.
AB  - We studied the functional and structural consequences of two novel missense
      mutations in CYP21 found in women with hyperandrogenism. The women were predicted
      to carry mutations by hormonal evaluation, but did not display any of the
      genotypes commonly associated with congenital adrenal hyperplasia. In one woman
      the novel mutation V304M was found in homozygous form. After expression in COS-1
      cells the mutated enzyme was found to have a residual activity of 46% for
      conversion of 17-hydroxyprogesterone and 26% for conversion of progesterone
      compared with the normal enzyme. The V304M variant thus represents the sixth
      known missense mutation associated with nonclassical disease. A normal
      degradation pattern for this mutant enzyme indicates that the missense mutation
      is of functional, rather than structural, importance. The other mutation, G375S,
      was detected in a young woman with signs of hyperandrogenism, in heterozygous
      form together with P453S, a mutation known to cause nonclassical congenital
      adrenal hyperplasia (her genotype was G375S+P453S/wild type). This novel variant
      almost completely abolished enzyme activity; conversion was 1.6% and 0.7% of
      normal for 17-hydroxyprogesterone and progesterone, respectively. These results
      underline the importance of genetic evaluation and counseling in hyperandrogenic
      women who are predicted to carry congenital adrenal hyperplasia-causing mutations
      by biochemical tests. It also supports the idea that the heterozygous carrier
      state for CYP21 mutations can be associated with symptoms of androgen excess in
      certain susceptible individuals.

PMID- 12050256
TI  - The in vivo control of prostaglandin H synthase-2 messenger ribonucleic acid
      expression in the human amnion at parturition.
AB  - Prostaglandin H synthase-2 (PGHS-2) activity and mRNA rise in the human amnion at
      late gestation, contributing to the increase in intrauterine PG production
      crucial for labor and delivery. In the present investigation we have determined
      the mechanism that controls amniotic PGHS-2 mRNA levels in vivo at term
      parturition. Amnion membranes were collected after elective cesarean section (n =
      20), and after spontaneous labor (n = 20). PGHS-2 relative gene transcription
      rates were determined by transcriptional run-on, and PGHS-2 mRNA and
      heterogeneous nuclear RNA (hnRNA) relative abundance were measured by
      quantitative real-time RT-PCR. The PGHS-2 mRNA degradation rate was determined by
      incubating amnion in the presence of the transcription inhibitor 5,6
      dichlorobenzimidazole riboside. The dynamics of PGHS-2 hnRNA and mRNA abundance
      were characterized in 0- to 24-h tissue incubations. The PGHS-2 relative gene
      transcription rate was a significant (P < 0.05) predictor of PGHS-2 hnRNA and
      mRNA abundance, and PGHS-2 hnRNA was also a predictor (P < 0.01) of PGHS-2 mRNA
      levels both before and after labor. Interestingly, even though PGHS-2 gene
      activity remained unchanged, PGHS-2 mRNA abundance increased with labor and
      displayed constitutive stability before and after labor. PGHS-2 mRNA levels
      spontaneously increased by 400% (P < 0.01) upon incubation for 24 h, whereas the
      transcription rate dropped by 95% during the first 2 h, then rebounded
      significantly between 6-24 h. Thus, PGHS-2 mRNA abundance is transcriptionally
      controlled in term amnion. Labor does not increase PGHS-2 gene activity or mRNA
      stability. The PGHS-2 gene is probably induced before labor by a factor(s)
      originating in the amnion membrane, and the resulting stable mRNA accumulates
      progressively in the tissue throughout labor and delivery.

PMID- 12050258
TI  - Trialkyltin compounds enhance human CG secretion and aromatase activity in human
      placental choriocarcinoma cells.
AB  - Human choriocarcinoma cell lines have been used as placental models for the study
      of endocrine function, including aromatase (CYP19) activity and the secretion of
      human CG (hCG). In the present study, we investigated the effects of trialkyltin
      compounds, which are suspected endocrine disrupters, on aromatase activity and
      hCG secretion in human choriocarcinoma JAR, JEG-3, and BeWo cells. Protein
      synthesis as measured by (35)S-methionine incorporation in all cell lines was
      markedly decreased by treatment with both tributyltin (TBT) and triphenyltin
      (TPT) at concentrations above 3 x 10(-7) M, due to cytotoxicity. In JAR cells,
      (35)S-methionine uptake was decreased by 50% at 3 x 10(-7) M of TBT. At a TPT
      concentration of 1 x 10(-7) M, protein synthesis in JAR cells was not affected,
      whereas JEG-3 and BeWo cells demonstrated slightly decreases. In all cell lines,
      both TBT and TPT increased levels of hCG secretion and aromatase activity in a
      dose- and time-dependent fashion following exposure to nontoxic concentration
      ranges. In addition, these trialkyltin compounds enhanced 8-bromo-cAMP-induced
      hCG secretion and aromatase activity in JAR cells. TBT caused dose-related
      increases in steady-state mRNA levels of both hCGbeta and CYP19 in JAR cells
      following 24- or 48-h exposure to nontoxic concentrations of TBT. However, these
      mRNA changes in JAR cells were not comparable to the changes in both hCG
      secretion and aromatase activity. These results indicate that the observed
      trialkyltin-induced alterations in human choriocarcinoma cells are due to other
      mechanism in addition to a regulation of hCG and CYP19 mRNA levels. Our studies
      suggest that trialkyltin compounds are potent stimulators of human placental hCG
      production and aromatase activity in vitro; and the placenta represents a
      potential target organ for trialkyltin compounds, whose endocrine-disrupting
      effects might be the result of local changes in hCG and estrogen concentrations
      in pregnant women.

PMID- 12050259
TI  - Short-term effects of glucocorticoids in the human fetal-placental circulation in
      vitro.
AB  - A number of studies demonstrate that both long-term and short-term exposure to
      glucocorticoids alters vascular function. We have examined whether the short-term
      administration of glucocorticoids into the human fetal-placental circulation
      affects placental arterial pressure and alters vascular responses to
      vasoconstrictive and vasodilator agents. Single lobules of term human placentae
      were bilaterally perfused in vitro with Krebs' solution (maternal and fetal, 5
      ml/min Krebs, 95% O2, 5% CO2, 37 C, pH 7.3), and changes in fetal-placental
      arterial perfusion pressure were measured. Dexamethasone (100 nM) infusion for 1
      h into the fetal-placental circulation caused a significant decrease in basal
      arterial pressure (n = 19, t test, P < 0.05). Continuous dexamethasone infusion
      (100 nM) did not alter vasoconstrictive responses to PGF(2alpha) (0.5-120 pM, n =
      12, ANOVA, P > 0.05) or potassium chloride (5-600 mM, n = 12, ANOVA, P > 0.05) or
      vasodilator responses to CRH (53-7400 pM, n = 13, ANOVA, P > 0.05). However when
      fetal-placental vessels were submaximally preconstricted and then infused with
      dexamethasone alone (40 nM-10 microM), there was a dose-dependent decrease in
      arterial pressure (n = 8). Dexamethasone-induced dilation was not inhibited by
      blocking nitric oxide synthase or cyclo-oxygenase activity. These data suggest
      that dexamethasone can cause dilation in the fetal-placental circulation,
      possibly via an endothelium-independent pathway.

PMID- 12050261
TI  - Modulation of endometrial redox balance during the menstrual cycle: relation with
      sex hormones.
AB  - This study aimed to evaluate the effects of changes in sex hormones occurring
      during the menstrual cycle on the redox balance and lipid peroxidation in normal
      human endometrial cells. Forty women, ages 21-41 yr, who were admitted to the
      Department of Gynecology and Obstetrics of the University of Bari for routine
      checkups or were treated for benign uterine disease, underwent endometrial biopsy
      and venipuncture. On the basis of histological examination, patients were
      allocated as follows: 10 in the early proliferative phase, 12 in the late
      proliferative phase, 8 in the early secretory phase, and 10 in the late secretory
      phase. LH, FSH (immunoradiometric essay), estradiol (E2), and progesterone (P(4))
      (RIA) were determined in plasma samples. On the endometrial specimens, total
      glutathione (GSH), oxidized GSH (GSSG), malondialdehyde, and GSH peroxidase
      activity (GSH-Px) were determined. Significant cycle-dependent changes in
      endometrial GSH-Px (P < 0.0001), GSH (P < 0.001), and GSSG as a percentage of GSH
      (P < 0.0001) were observed. Malondialdehyde did not show significant differences.
      A linear regression model correlating sex hormone changes with redox indexes was
      performed. A significant positive correlation was observed between E2 and GSH-Px
      (r = 0.74; P = 0.0001), E2 and GSSG, as percentage of total (r = 0.84; P <
      0.0001); a negative correlation was found between E2 and GSH (r = -0.57; P =
      0.0001). No significant correlation was found between P(4) or FSH and oxidative
      balance. LH was found to be correlated with GSH-Px (r = 0.66; P = 0.0001) and
      GSSG as percentage of GSH (r = 0.5; P < 0.001). We conclude that the hormonal
      pattern is involved in maintaining the optimal redox balance in endometrium,
      mainly through modulation of GSH level and metabolism.

PMID- 12050262
TI  - Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated
      steroidogenesis in human granulosa and theca cells.
AB  - Growth differentiation factor-9 (GDF-9), a member of the transforming growth
      factor superfamily, modulates the development and function of granulosa and theca
      cells. Targeted deletion of GDF-9 in the mouse revealed that GDF-9 was essential
      for the establishment of the thecal cell layer during early folliculogenesis.
      During later stages of follicular development, the roles of GDF-9 are less well
      understood, but it has been postulated that oocyte-derived GDF-9 may prevent
      premature luteinization of follicular cells, based on its ability to modulate
      steroidogenesis by rodent ovarian cells. In the rodent, GDF-9 is expressed solely
      by the oocyte from the early primary follicular stage through ovulation. Recent
      studies in the rhesus monkey demonstrated that granulosa cells express GDF-9,
      suggesting a broader role for this protein in ovarian function in primates. We
      examined the effect of recombinant GDF-9 on proliferating human granulosa and
      thecal cell steroidogenesis and the expression of steroidogenic acute regulatory
      protein (StAR), P450 side-chain cleavage, and P450 aromatase. We also examined
      granulosa cell GDF-9 expression by quantitative RT-PCR and by Western analysis.
      GDF-9 inhibited 8-Br-cAMP-stimulated granulosa progesterone synthesis by
      approximately 40%, but did not affect basal progesterone production. Concordant
      with reduced steroid production, 8-Br-cAMP-stimulated StAR protein expression was
      reduced approximately 40% in granulosa cells, as were expression of StAR mRNA and
      StAR promoter activity. Additionally, GDF-9 inhibited 8-Br-cAMP-stimulated
      expression of P450 side-chain cleavage and P450 aromatase. Human granulosa cells
      expressed GDF-9, as determined by RT-PCR and Western analysis. Treatment of human
      thecal cells with GDF-9 blocked forskolin-stimulated progesterone, 17alpha
      hydroxyprogesterone, and dehydroepiandrosterone synthesis. Thecal cells exhibited
      greater sensitivity to GDF-9, suggesting that this cell may be a primary target
      of GDF-9. Moreover, GDF-9 increased thecal cell numbers during culture, but had
      no effect on granulosa cell growth. Our findings implicate GDF-9 in the
      modulation of follicular steroidogenesis, especially theca cell function. Because
      GDF-9 mRNA and protein are detectable in granulosa-lutein cells after the LH
      surge, the concept of GDF-9 as a solely oocyte-derived luteinization inhibitor
      needs to be reevaluated.

PMID- 12050263
TI  - Pituitary function in a man with congenital aromatase deficiency: effect of
      different doses of transdermal E2 on basal and stimulated pituitary hormones.
AB  - To clarify the role of estrogen on male pituitary function, the effects of
      different doses of transdermal E2 on pituitary secretion were evaluated in a man
      with aromatase deficiency. The study protocol was divided into the following
      three phases: no E2 treatment (phase 1); 25 microg transdermal E2 twice weekly
      for 9 months (phase 2);12.5 microg transdermal E2 twice weekly for 9 months
      (phase 3). Pituitary function was studied in detail during each phase of the
      study protocol by measuring hormone levels in basal conditions and after dynamic
      testing (GnRH, insulin tolerance test, GHRH plus arginine, TRH, and corticotropin
      releasing factor; tests). Basal and GnRH-stimulated gonadotropin levels resulted
      inversely related to E2 serum levels, according to the dosage of estrogen
      administered. Basal and stimulated GH, PRL, and TSH serum levels did not change
      during the protocol study. The secretory pituitary reserve of GH was clearly
      impaired. Basal and stimulated ACTH and cortisol serum levels were not modified
      by estrogen administration. This study demonstrated that in the human male E2 is
      required at pituitary level for normal functioning of gonadotropin feedback both
      in basal and stimulated conditions. In this patient GH deficiency seems to be an
      adult-onset event since he reached a tall stature. However, the finding of a
      severe impairment in GH response to potent provocative stimuli together with the
      insensitivity of GH/IGF-I axis to circulating estrogens strongly suggest a
      possible involvement of estrogens on both the development and maturation of the
      somatotrophic axis. Finally, the congenital lack of estrogen activity seems to be
      associated with a slightly impaired secretion of PRL and TSH, suggesting a
      possible role of estrogens on the pituitary secretion of these hormones in the
      human male.

PMID- 12050264
TI  - Increased orderliness of growth hormone (GH) secretion in GH-deficient adults
      with low serum insulin-like growth factor I.
AB  - Available studies suggest that a proportion of GH-deficient (GHD) adults maintain
      serum IGF-I concentrations within the age- and sex-matched normal range. The
      basis for this distinction is not known. In this study 24-h GH profiles (sampling
      every 30 min) were appraised in five GHD adults with low serum IGF-I
      concentrations (<2 SD of the age- and sex-matched normal range), five GHD adults
      with normal serum IGF-I levels (within +/-2 SD), and five healthy subjects.
      Serial GH concentrations, measured using a chemiluminescence assay, were analyzed
      by deconvolution and approximate entropy (ApEn; regularity) analyses. The
      apparent half-duration of GH secretory bursts was longer in both GHD groups than
      in the healthy controls, as determined by deconvolution analysis (P < 0.05 each).
      The GH burst frequency was higher, the interburst interval was shorter, and the
      GH burst amplitude was lower in GHD adults with normal serum IGF-I than in
      healthy controls (P < 0.05, P < 0.05, and P < 0.01, respectively). The percentage
      of total daily GH secretion that was pulsatile was also reduced in the GHD adults
      with normal serum IGF-I compared with the other two groups (P < 0.05 and P <
      0.05, respectively). In contrast, ApEn ratios were lower in the GHD adults with
      low serum IGF-I than in the GHD adults with normal IGF-I and controls (P < 0.01
      and P < 0.05, respectively). Serum IGF-I concentrations correlated positively
      with ApEn ratios in the total study population (n = 15) and in the GHD adults (n
      = 10). In conclusion, 24-h patterns of GH release differed in GHD adults with low
      vs. normal serum IGF-I concentrations. GHD adults with low IGF-I levels maintain
      low ApEn ratios (denoting greater relative orderliness of GH secretion), whereas
      GHD patients with normal IGF-I values generate a high frequency, low amplitude GH
      output. The foregoing contrasts point to distinct neuroendocrine features of the
      GH-deficient state of adults, which can be related to concurrent IGF-I
      production.

PMID- 12050266
TI  - Additive effects of insulin-sensitizing and anti-androgen treatment in young,
      nonobese women with hyperinsulinism, hyperandrogenism, dyslipidemia, and
      anovulation.
AB  - The endocrine-metabolic hallmarks of polycystic ovary syndrome are
      hyperinsulinism, hyperandrogenism, dyslipidemia, and anovulation. We hypothesized
      that dyslipidemia and anovulation in nonobese women with polycystic ovary
      syndrome are essentially secondary to the concerted effects of hyperandrogenism
      and insulin resistance. We tested this hypothesis by comparing the efficacy of
      anti-androgen (flutamide) or insulin-sensitizing (metformin) monotherapy to that
      of combined therapy in normalizing the endocrine-metabolic and anovulatory status
      of nonobese, young women with hyperinsulinemic hyperandrogenism. Thirty-one young
      women (mean age, 18.7 yr; body mass index, 21.9 kg/m(2); hirsutism score, 16;
      monthly ovulation rate monitored by weekly serum progesterone, 10%) were randomly
      assigned to receive once daily flutamide (250 mg; n = 10), metformin (1275 mg; n
      = 8), or combined flutamide- metformin therapy (n = 13) for 9 months. At
      baseline, there were no endocrine-metabolic differences among treatment groups.
      Compared with monotherapy, combined flutamide-metformin therapy resulted in
      greater improvements in insulin sensitivity, in testosterone, androstenedione,
      dehydroepiandrosterone sulfate, and triglyceride levels, and in low-density
      lipoprotein/high-density lipoprotein-cholesterol ratio (all P < 0.005). Monthly
      ovulation rates increased after 9 months to 75 and 92%, respectively, with
      metformin alone or with combined therapy, but were unimproved with flutamide
      alone. All treatments were well tolerated. In conclusion, combined anti-androgen
      and insulin-sensitizing treatment in young, nonobese women with hyperinsulinemic
      hyperandrogenism had additive benefits on insulin sensitivity, hyperandrogenemia,
      and dyslipidemia. The data from this small study suggest that dyslipidemia is
      secondary to excess androgen action in concert with the hyperinsulinemia
      associated with insulin resistance. In contrast, anovulation seems to be mainly
      attributable to insulin resistance and hyperinsulinemia.

PMID- 12050267
TI  - Placental GH, IGF-I, IGF-binding protein-1, and leptin during a glucose challenge
      test in pregnant women: relation with maternal body weight, glucose tolerance,
      and birth weight.
AB  - The prediction of birth weight may be improved by the measurement of hormones or
      growth factors in the mother. We measured body weight (BW) and plasma levels of
      placental GH (PGH), IGF-I, IGF-binding protein-1 (IGFBP-1), and leptin at the
      time of the glucose challenge test (GCT) in 289 women, who were pregnant with a
      single fetus, between 24 and 29 wk gestational age (GA). Delivery occurred 12 +/-
      2 (mean +/- SD) wk later. First, we examined which variables regulate these
      hormonal factors. Multiple regression showed that PGH concentrations were
      determined by GA at sampling and were negatively related to BW. IGF-I levels were
      mainly determined by PGH, and also by insulin, BW, and (negatively) age. IGFBP-1
      concentrations were negatively determined by BW, insulin, and IGF-I. BW was also
      a powerful determinant of leptin levels, with insulin as a less robust
      determinant. Second, we examined the relation to glucose levels. PGH, IGF-I, and
      IGFBP-1 concentrations were not correlated with post-GCT glucose levels and were
      comparable in women with a normal or disturbed GCT (glucose >/=7.8 mmol/liter; n
      = 72). Finally, we examined the relation with birth weight and placental weight.
      Birth weight, corrected for GA and stratified into percentile groups, and the
      ponderal index at birth were strongly related to maternal BW, but not to maternal
      PGH, IGF-I, or IGFBP-1 levels. Neither was maternal leptin related to birth
      weight, but leptin concentrations were slightly higher in women who delivered
      obese babies. Placental weight was not related to any of the hormonal factors.
      This prospective study indicates that the variation in circulating PGH, IGF-I,
      IGFBP-1, and leptin between 24 and 29 wk of pregnancy is strongly dependent on
      maternal BW, but is unrelated to glucose tolerance. In addition, the measurement
      of PGH, IGF-I, IGFBP-1, or leptin at the time of the GCT is not useful clinically
      to predict birth weight.

PMID- 12050268
TI  - Effects of recombinant human IGF-I and oral contraceptive administration on bone
      density in anorexia nervosa.
AB  - Over 90% of women with anorexia nervosa demonstrate osteopenia, and almost 40%
      demonstrate osteoporosis at one or more skeletal sites. In addition to estrogen
      deficiency causing an increase in bone resorption, nutritional effects on the GH
      IGI-I axis may contribute to the severe bone loss in this population by
      decreasing bone formation. We tested the hypothesis that recombinant human IGF-I
      (rhIGF-I) would increase bone density in women with anorexia nervosa and
      furthermore assessed the effects of combined rhIGF-I and oral contraceptive
      administration (OCP) in this population. Sixty osteopenic women with Diagnosis
      and Statistical Manual of Mental Disorders IV Revised confirmed anorexia nervosa
      [age (25.2 +/- 0.7 yr, range 18-38 yr), body mass index (17.8 +/- 0.3 kg/m(2) ),
      spinal bone mineral density T score (-2.1 +/- 0.1 SD) were randomized to one of
      four treatment groups [rhIGF-I (30 microg/kg sc twice daily) and a daily oral
      contraceptive (Ovcon 35, 35 microg ethinyl estradiol and 0.4 mg norethindrone],
      rhIGF-I alone (30 microg/kg sc twice daily), oral contraceptive alone, or neither
      treatment for 9 months. All subjects received calcium 1500 mg/d and a standard
      multivitamin containing 400 IU of vitamin D. Administration of rhIGF-I was
      placebo controlled and blinded to subjects. The rhIGF-I was titrated to maintain
      IGF-I levels within the age-adjusted normal range for each patient and was well
      tolerated. The effects of rhIGF-I and OCP were analyzed simultaneously among all
      subjects in a factorial analysis and in an analysis of the four individual
      treatment groups. Anteroposterior spinal bone density increased significantly in
      response to rhIGF-I (1.1% +/- 0.5% vs. -0.6% +/- 0.8%, P = 0.05, all rhIGF-I vs.
      all placebo treated, respectively, by analysis of covariance). In contrast, OCP
      did not result in increased bone density (0.8% +/- 0.6% vs. -0.4% +/- 0.8%, P =
      0.21, all OCP vs. all non-OCP treated, respectively, by analysis of covariance).
      However, bone density increased to the greatest extent in the combined treatment
      group (rhIGF-I and OCP), compared with control patients receiving no active
      therapy (1.8% +/- 0.8% vs. 0.3% +/- 0.6% vs. -0.2% +/- 0.8% vs. -1.0% +/- 1.3%,
      rhIGF-I and OCP vs. rhIGF-I alone vs. OCP alone vs. no active therapy, P < 0.05
      for rhIGF-I and OCP vs. no active therapy). These data demonstrate that
      osteopenic women with anorexia nervosa treated with rhIGF-I showed more
      beneficial changes in bone density, compared with patients not treated with rhIGF
      I. Antiresorptive therapy with OCP is not sufficient to improve bone density in
      undernourished patients, but such therapy may augment the effects of rhIGF-I in a
      combined treatment strategy. Further long-term studies are needed to investigate
      the effects of rhIGF-I and combined anabolic/antiresorptive strategies on bone in
      women with anorexia nervosa.

PMID- 12050269
TI  - Evidence that the IL-6/IL-6 soluble receptor cytokine system plays a role in the
      increased skeletal sensitivity to PTH in estrogen-deficient women.
AB  - Estrogen-deficient women show increased skeletal sensitivity to the resorbing
      actions of PTH. The basis for this effect is not known. To examine the influence
      of estrogen deficiency on PTH-induced proresorptive cytokine production in
      humans, the response of five young women to a 36-h infusion of (1-34)human PTH
      (hPTH) was studied. PTH induced significant increases in circulating levels of IL
      6 (mean values, T(0)-->T(36 h); 2.2-->19.2 pg/ml), IL-6 soluble receptor (IL-6sR;
      29.8-->67.2 ng/ml), urine N-telopeptide of type I collagen (NTX) (38.6-->148 nM
      bone collagen equivalent/mM creatinine) and serum calcium (2.12-->2.62
      mmol/liter). To examine the impact of hormonal status on this response, PTH
      infusions were next undertaken in seven estrogen-deficient and seven estrogen
      treated postmenopausal women. When compared with estrogen-treated women, and
      correcting for differences in baseline values, estrogen-deficient women
      demonstrated an exaggerated increase in circulating levels of IL-6 (5.0-->31.7
      vs. 3.2-->14.4 pg/ml; P = 0.0001) and IL-6sR (49.2-->102.1 vs. 37.7-->66.7; P =
      0.0001). This was accompanied by greater increases in NTX excretion in the
      estrogen-deficient women (61.2-->201.6 vs. 44.8-->114.8, E(-) vs. E(+), P =
      0.0001). Estrogen deficiency was not associated with augmented PTH-induced
      increases in colony-stimulating factor-1, IL-1beta, IL-11, or TNF-alpha. In a
      multiple regression model controlling for group, age, years since menopause both
      IL-6 and IL-6sR were strong predictors of NTX. These data, along with previous
      animal studies, support the conclusion that the IL-6/IL-6SR cytokine system plays
      a role in the increased skeletal sensitivity to PTH seen in estrogen-deficient
      women.

PMID- 12050270
TI  - Comparison of insulin sensitivity, clearance, and secretion estimates using
      euglycemic and hyperglycemic clamps in children.
AB  - The euglycemic clamp is the gold standard for estimating insulin sensitivity. The
      hyperglycemic clamp is easier to perform and is the gold standard for estimating
      beta-cell secretion. Reports in adults suggest that hyperglycemic clamps can
      estimate insulin sensitivity with results equivalent to euglycemic clamps. We
      investigated whether insulin sensitivity measures from both clamps are equivalent
      in children. Thirty-one lean and obese children (mean body mass index, 25.1 +/-
      4.9 kg/m(2); mean age, 8.7 +/- 1.4 yr; 15 girls and 16 boys; 12 black and 19
      white) were studied. All subjects underwent hyperglycemic clamps, then euglycemic
      clamps 2-6 wk later. Body composition was estimated by dual energy x-ray
      absorptiometry. Visceral and sc abdominal fat was estimated by abdominal magnetic
      resonance imaging. Whole-body glucose disposal and insulin sensitivity (SI clamp)
      derived from both clamps and normalized for total or visceral fat and lean mass
      were significantly correlated (r, 0.45-0.65; P < 0.05). However, absolute SI
      clamp values were not equivalent. Bland-Altman comparisons found that SI clamp
      estimates from hyperglycemic clamps became less precise as SI clamp increased.
      There were significant correlations between indices of beta-cell secretion from
      the hyperglycemic clamp and mean C-peptide values from the euglycemic clamp (P <
      0.05). However, no correlation was found between measures of total insulin
      clearance (derived from the euglycemic clamp) and surrogates of hepatic insulin
      clearance (derived from the hyperglycemic clamp). In this cohort of diverse
      children, SI clamp values from euglycemic and hyperglycemic clamps were
      significantly correlated but were not equivalent, whereas the insulin clearance
      measures were not correlated. It cannot be assumed that the hyperglycemic clamp
      obviates the need for euglycemic clamp studies to accurately estimate insulin
      sensitivity in children.

PMID- 12050271
TI  - QUICKI is useful for following improvements in insulin sensitivity after therapy
      in patients with type 2 diabetes mellitus.
AB  - To investigate whether quantitative insulin sensitivity check index (QUICKI)
      would be useful as an index of insulin resistance during the clinical course of
      type 2 diabetes mellitus, correlation between QUICKI and the index of the
      euglycemic hyperinsulinemic clamp study [clamp insulin resistance (clamp IR)] was
      evaluated in 60 patients with type 2 diabetes mellitus before and after
      treatment. The therapy program consisted of diet (1440-1720 kcal/d) and exercise
      (walking 10,000 steps daily) for 6 wk. QUICKI and clamp IR were significantly
      correlated before (r = 0.598, P < 0.0001) and after (r = 0.583, P < 0.0001)
      treatment. Neither the slope nor the intercept of the linear correlation between
      QUICKI and clamp IR measured before treatment was significantly different from
      those measured after treatment (slopes; F = 0.002, P = 0.96, intercepts; F =
      2.65, P = 0.11). During treatment, the values of both QUICKI (8% change; P <
      0.0001) and clamp IR (38% change; P < 0.0001) significantly increased and their
      changes were significantly correlated (r = 0.415, P < 0.01). In conclusion,
      QUICKI may become a useful method for the follow-up of insulin resistance during
      the treatment of patients with type 2 diabetes mellitus.

PMID- 12050272
TI  - Leptin gene polymorphism is associated with hypertension independent of obesity.
AB  - Leptin is an adipocyte-derived hormone that regulates food intake and energy
      expenditure. Recent functional studies have suggested a direct effect of leptin
      on blood pressure. In this study we examined the genetic association of the
      leptin gene polymorphism with obesity, insulin resistance, and hypertension. A
      highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region
      of the leptin gene was examined. The alleles of the polymorphism consisted of two
      groups with different size distributions: a shorter one (class I) and a longer
      one (class II). The frequency of class I/class I genotype was much higher in
      hypertensive subjects than in control subjects (13.5% vs. 3.4%; P = 0.0027). No
      significant difference in body mass index was observed with different genotypes
      in either patients with hypertension or control subjects. Insulin responses to
      glucose and insulin sensitivity were not different among patients with different
      genotypes. The leptin gene polymorphism was associated with hypertension
      independent of obesity. These data together with recent functional data on the
      direct effect of leptin on blood pressure suggest that the leptin gene and its
      product, leptin, are an attractive target for studies on the mechanisms of
      hypertension and for the development of methods for the prediction, prevention,
      and therapy for hypertension.

PMID- 12050273
TI  - FFA-induced endothelial dysfunction can be corrected by vitamin C.
AB  - Insulin resistance is associated with an inappropriate elevation of plasma FFA
      and endothelial dysfunction. FFA could stimulate formation of reactive oxygen
      species, which could be responsible for vascular impairment. In this randomized,
      double-blind, cross-over study in 10 healthy volunteers (24 +/- 3 yr old),
      forearm blood flow (FBF) responses to intraarterial acetylcholine (ACh) and
      glyceryl trinitrate were assessed with coadministration of vitamin C (24 mg/ml)
      or placebo, respectively, in the presence of increased plasma FFA induced by
      Intralipid/heparin infusion. The rise in plasma FFA from 320 +/- 64 to 1852 +/-
      232 micromol/liter was associated with a reduced response of FBF to ACh by 55% (P
      < 0.01). During coadministration of vitamin C, the impaired responsiveness of FBF
      to ACh was completely reversed and not different from that observed under
      baseline conditions. Vitamin C did not affect plasma FFA concentrations. Glyceryl
      trinitrate responsiveness was unchanged during FFA elevation, with or without
      vitamin C. These data suggest that FFA-induced vascular oxidative stress could
      contribute to endothelial dysfunction in insulin-resistant patients. High
      concentrations of antioxidants are able to reverse the local effects of FFA on
      endothelium-dependent vasodilation.

PMID- 12050274
TI  - Hyperglycemic clamp assessment of insulin secretory responses in normal subjects
      treated with olanzapine, risperidone, or placebo.
AB  - The goal of this study was to evaluate the effect of olanzapine or risperidone
      treatment on beta-cell function in healthy volunteers. Subjects were randomly
      assigned to single-blind therapy with olanzapine (10 mg/d; n = 17), risperidone
      (4 mg/d; n = 13), or placebo (n = 18) for 15-17 d. Insulin secretion was
      quantitatively assessed at baseline and the end of the study period using the
      hyperglycemic clamp. Weight increased significantly (P < 0.01) in the olanzapine
      (2.8 +/- 1.7 kg) and risperidone (3.1 +/- 2.1 kg) treatment groups. An increase (
      approximately 25%) in the insulin response to hyperglycemia and a decrease (
      approximately 18%) in the insulin sensitivity index were observed after treatment
      with olanzapine and risperidone. The change in insulin response was correlated (r
      = 0.5576; P = 0.019) with a change in body mass index. When the impact of weight
      change was accounted for by multivariate regression analyses, no significant
      change in insulin response or insulin sensitivity was detected after treatment
      with olanzapine or risperidone. We found no evidence that treatment of healthy
      volunteers with olanzapine or risperidone decreased the insulin secretory
      response to a prolonged hyperglycemic challenge. The results of this study do not
      support the hypothesis that olanzapine or risperidone directly impair pancreatic
      beta-cell function.

PMID- 12050275
TI  - Progesterone withdrawal and estrogen activation in human parturition are
      coordinated by progesterone receptor A expression in the myometrium.
AB  - In human parturition, progesterone withdrawal and estrogen activation are not
      mediated by changes in progesterone and estrogen levels. Instead, these events
      could be facilitated by changes in the responsiveness of the myometrium to
      progesterone and estrogens via changes in PR and ER expression. We hypothesized
      that functional progesterone withdrawal occurs by increased expression of the
      type A PR (PR-A), which suppresses progesterone responsiveness, and that
      functional estrogen activation occurs by increased myometrial expression of
      ERalpha and/or ERbeta. To test this hypothesis we compared the abundance of mRNAs
      (assessed by quantitative RT-PCR) encoding PR-A, PR-B, ERalpha, and ERbeta in
      nonlaboring (n = 12) and laboring (n = 12) term human myometrium. PR-A, PR-B, the
      PR-A/PR-B mRNA ratio, and ERalpha mRNA were significantly increased in laboring
      myometrium, whereas ERbeta mRNA was low and unchanged. The PR-A/PR-B mRNA ratio
      correlated positively with ERalpha mRNA levels in nonlaboring myometrium and with
      HOXA10 mRNA levels in laboring myometrium. Because progesterone inhibits ERalpha
      and HOXA10 expression, these findings indicate that myometrial progesterone
      responsiveness is inversely related to the extent of expression of PR-A relative
      to PR-B. ERalpha mRNA levels correlated positively with cyclooxygenase type 2 and
      oxytocin receptor mRNA levels in nonlaboring myometrium, indicating that the
      increase in ERalpha expression is directly associated with the activation of
      contraction-associated genes and estrogen responsiveness. These data indicate
      that in the term human myometrium, responsiveness to progesterone is controlled
      by the expression of PR-A relative to PR-B and that a significant increase in
      this ratio underlies functional progesterone withdrawal. Our data also indicate
      that functional estrogen activation occurs by increased expression of ERalpha and
      is linked to functional progesterone withdrawal. Interaction between the PR and
      ER systems in the human myometrium may be critical for the control of human
      parturition and the coordination of progesterone withdrawal and estrogen
      activation required for parturition.

PMID- 12050276
TI  - Quantification of the soluble leptin receptor in human blood by ligand-mediated
      immunofunctional assay.
AB  - Panels of monoclonal antibodies (mAbs) were raised against recombinant human
      leptin and the recombinant human soluble leptin receptor. Using these mAbs, we
      established a ligand-mediated immunofunctional assay (LIFA) to quantify
      concentrations of the soluble leptin receptor, which has been shown to be a major
      binding protein for leptin in human serum. In performing the assay, a monoclonal
      antibody (mAb 2H6) against the soluble leptin receptor, which binds an epitope
      outside the leptin-binding site and equally recognizes both, free and leptin
      occupied soluble leptin receptor, is used to capture the soluble leptin receptor
      on a microtiter plate. Recombinant human leptin is added to saturate all binding
      sites, and a biotinylated anti-leptin mAb (4D3) detects the amount of leptin
      (endogenous and exogenous) bound to the soluble leptin receptor. The same
      procedure, but without adding exogenous leptin, allows for measurement of the
      circulating endogenous leptin/soluble leptin receptor complexes. The LIFA assay
      has a linear working range of 0.5-200 microg/liter, intra- and interassay
      coefficients of variation ranged from 3.2-6.3% and from 5.2-7.9%, respectively.
      The assay has a linearity of 102.2 +/- 5.2% (mean +/- SD) and a recovery of 100.7
      +/- 6.9%. Size-exclusion chromatography revealed that the assay measures a
      protein with a main peak eluted at 340 kDa. The soluble leptin receptor
      concentration (63.3 +/- 22.8 microg/liter (mean +/- SD), range 17.9-129.2
      microg/liter, n = 43) in normal subjects (body mass index = 22.3 +/- 2.3 kg/m(2))
      was not different from the concentration (54.4 +/- 19.8 microg/liter, range 23.7
      104.8 microg/liter, n = 34, P > 0.05) found in obese subjects (body mass index =
      40.9 +/- 15.7 kg/m(2)). However, the percentage of the total soluble leptin
      receptor complexed with endogenous leptin was significantly higher in obese
      subjects, compared with normal subjects (74.9% +/- 23.5% vs. 33.1% +/- 19.5%, P <
      0.001). Higher serum leptin levels in obese subjects (38.4 +/- 23.7 microg/liter
      vs. 7.8 +/- 5.5 microg/liter in normal subjects, P < 0.001) together with
      comparable soluble leptin receptor levels result in a lower proportion of leptin
      bound to the soluble leptin receptor in obese subjects (19.3% +/- 19.4%, range
      4.9-97.2%) than in normal subjects (39.0% +/- 22.5%, range 15.3-96.5%, P <
      0.001). The development of this LIFA for the rapid and accurate quantification of
      total soluble leptin receptor and circulating leptin/soluble leptin receptor
      complexes provides a valuable tool for the further understanding of the role of
      leptin and its soluble receptor in health and disease.

PMID- 12050277
TI  - Vitamin E supplementation reduces plasma vascular cell adhesion molecule-1 and
      von Willebrand factor levels and increases nitric oxide concentrations in
      hypercholesterolemic patients.
AB  - Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and reduced nitric
      oxide (NO) availability represent early characteristics of atherosclerosis. To
      evaluate whether the antioxidant vitamin E affected the circulating levels of
      soluble VCAM-1 (sVCAM-1) and the plasma metabolite of NO (nitrite+nitrate) in
      hypercholesterolemic patients, either vitamin E (either 400 IU or 800 IU/d for 8
      wk) or placebo were randomly, double-blindly given to 36 hypercholesterolemic
      patients and 22 age- and sex-matched controls. At baseline hypercholesterolemic
      patients showed higher plasma sVCAM-1 (microg.liter(-1)) (591.2 +/- 132.5 vs.
      505.0 +/- 65.6, P < 0.007) and lower NO metabolite (microM) levels (15.9 +/- 3.4
      vs. 29.2 +/- 5.1, P < 0.0001) than controls. In hypercholesterolemic patients, 8
      wk vitamin E (but not placebo) treatment significantly decreased circulating
      sVCAM-1 levels (400 IU: -148.9 +/- 84.6, P < 0.009; 800 IU: -204.0 +/- 75.7, P <
      0.0001; placebo: -4.7 +/- 22.6, NS), whereas it increased NO metabolite
      concentrations (400 IU: +4.0 +/- 1.7, P < 0.02; 800 IU: +5.5 +/- 0.8, P < 0.0001;
      placebo: +0.1 +/- 1.1, NS) without affecting circulating low- density lipoprotein
      levels. Changes in both plasma sVCAM-1 and NO metabolite levels showed a trend to
      significantly correlate (r = -0.515, P = 0.010; and r = 0.435, P = 0.034,
      respectively) with changes in vitamin E concentrations induced by vitamin E
      supplementation. In conclusion, isolated hypercholesterolemia both increased
      circulating sVCAM-1 and reduced NO metabolite concentrations. Vitamin E
      supplementation counteracts these alterations, thus representing a potential tool
      for endothelial protection in hypercholesterolemic patients.

PMID- 12050278
TI  - Close juxtapositions between LHRH immunoreactive neurons and substance P
      immunoreactive axons in the human diencephalon.
AB  - LHRH release is induced by substance P (SP) in the rat hypothalamus. Recent
      immunocytochemical studies indicate that SP-immunoreactive axons synapse on LHRH
      neurons in the diencephalon of the rat, but this phenomenon has not yet been
      demonstrated in human. Therefore, in the present study we visualized the SP- and
      LHRH-immunoreactive (IR) elements in the human diencephalon and evaluated the
      close juxtapositions between them. The distribution of LHRH- and SP-IR sites were
      investigated in diencephalic sections of six, postmortem human brains by means of
      double-labeling immunocytochemistry. The LHRH-containing perikarya were located
      in the diagonal band of Broca, lamina terminalis cinerea, preopticoseptal, medial
      preoptic, and infundibular areas of the brain. The SP-IR fibers formed a network
      in the periventricular zone in the infundibular region, median eminence, and
      corpus striatum. The SP-IR cell bodies were located mainly in the infundibular
      region, median eminence, basal part of the periventricular area, dorsomedial
      subdivision of the ventromedial nucleus, and basal perifornical area of the
      tuberal region. The juxtapositions between LHRH-IR cell bodies and SP-IR
      varicosities were detected in the infundibular and periventricular regions. In
      these sites black, silver-intensified, SP-IR fiber varicosities abutted on brown,
      DAB-labeled, LHRH-IR cell bodies. Similar structures were detected between the SP
      IR fibers and SP-IR perikarya. These findings suggest that the juxtapositions
      between the SP and LHRH systems may be the morphological basis of SP-controlled
      LHRH release in the human diencephalon. Moreover, the intimate contacts between
      SP-IR fiber varicosities and SP-IR cell bodies or axons indicate direct control
      of SP on the diencephalic SP release.

PMID- 12050279
TI  - Uterine glands provide histiotrophic nutrition for the human fetus during the
      first trimester of pregnancy.
AB  - Providing adequate nutrition to the fetus is key to a successful pregnancy. The
      interstitial form of implantation displayed by the human blastocyst is generally
      associated with early onset of maternal blood flow to the developing placenta,
      and hence hemotrophic exchange. However, the recent finding that the maternal
      intraplacental circulation is not fully established until the third month of
      gestation suggests that human fetal nutrition may be initially histiotrophic. We
      therefore investigated activity of the uterine glands during early pregnancy. We
      demonstrate here that these glands remain active until at least wk 10 of
      pregnancy, and that their secretions are delivered freely into the placental
      intervillous space. We also demonstrate phagocytic uptake by the placental
      syncytiotrophoblast of two glycoproteins, the mucin MUC-1 and glycodelin A,
      synthesized in the maternal glands. Glycodelin was also detected within the
      epithelium of the secondary yolk sac lining the exocoelomic cavity, indicating
      that the yolk sac may play an important role in nutrient exchange before
      vascularisation of the chorionic villi. Our findings demonstrate that the uterine
      glands are an important source of nutrients during organogenesis, when metabolism
      is essentially anaerobic.

PMID- 12050280
TI  - Steroid receptor coactivator expression throughout the menstrual cycle in normal
      and abnormal endometrium.
AB  - The endometrium of reproductive aged women undergoes cyclic developmental changes
      in preparation for implantation in response to estrogen and progesterone. These
      steroids and their receptors are tightly regulated throughout the menstrual
      cycle, and their actions are facilitated by the presence of steroid receptor
      coactivators of the p160 family. In this study using immunohistochemistry and
      Western blot analysis, we characterize the expression patterns of three
      coactivators, steroid receptor coactivator-1, amplified in breast cancer-1
      (AIB1), and transcriptional intermediary factor-2 in human endometrium obtained
      prospectively from normal fertile women throughout the menstrual cycle. With the
      exception of glandular AIB1, which increased in the late secretory phase, none of
      the coactivators changed significantly during the menstrual cycle. We compared
      coactivator expression patterns in fertile endometrium to the endometrium of
      anovulatory (proliferative; n = 3) and clomiphene-induced ovulatory (secretory; n
      = 13) women with polycystic ovarian syndrome (PCOS), a group that have a higher
      likelihood of developing estrogen-induced endometrial hyperplasia and cancer. To
      control for the effect of clomiphene citrate, an additional group was included
      consisting of ovulatory women treated with clomiphene citrate for "male factor"
      infertility. Compared with both fertile and infertile controls, PCOS women
      exhibited elevated levels of AIB1 and transcriptional intermediary factor-2
      expression in both epithelial and stromal cells. We postulate that increased
      coactivator expression may render the endometrium more sensitive to estrogen. In
      support of this, we describe an increased expression of ERalpha (an estrogen
      induced gene product) during the menstrual cycle in PCOS endometrium compared
      with fertile controls. In summary, we demonstrate that the expression of p160
      coactivators are regulated in endometrium during the menstrual cycle in normal
      fertile women but are overexpressed in the endometrium of women with PCOS. Based
      on these findings, we suggest a possible mechanism to explain the poor
      reproductive performance observed in PCOS and the increased incidence of
      endometrial hyperplasia and cancer noted in this group of women.

PMID- 12050281
TI  - 25-hydroxyvitamin D(3)-1alpha-hydroxylase expression in normal and pathological
      parathyroid glands.
AB  - Active vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], plays a pivotal
      role in calcium homeostasis and bone metabolism. Circulating levels of
      1,25(OH)(2)D(3) are thought to be dependent mainly on the activity of the renal
      cytochrome P450 enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha
      hydroxylase), which is potently induced by PTH. However, 1alpha-hydroxylase
      activity or expression has also been reported at several extrarenal sites, at
      which local synthesis of 1,25(OH)(2)D(3) appears to fulfill autocrine or
      paracrine functions. This includes tissues such as placenta and brain that also
      express LRP-2/megalin, an endocytic receptor for multiple ligands, which is
      involved in the renal uptake of the substrate for 1alpha -hydroxylase, 25
      hydroxyvitamin D(3). We have previously demonstrated LRP-2/megalin in parathyroid
      cells, and here we present results from RT-PCR and immunohistochemical analyses
      showing coincident expression of 1alpha-hydroxylase in normal and pathological
      parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression
      of 1alpha-hydroxylase mRNA was higher in the majority of parathyroid adenomas and
      secondary hyperplastic glands but lower in parathyroid carcinomas, compared with
      normal parathyroid tissue. The findings imply that in addition to feedback
      control by circulating 1,25(OH)(2)D(3) levels, parathyroid cells may also be
      influenced by local 1alpha -hydroxylase activity with possible growth regulatory
      and differentiating effects.

PMID- 12050282
TI  - Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR
      "knockout".
AB  - Mutations in the GnRH receptor (GnRHR) have been shown to be responsible for a
      significant number of autosomic recessive and, less commonly, sporadic cases of
      idiopathic hypogonadotropic hypogonadism. We describe a woman with complete GnRH
      resistance secondary to a novel homozygous GnRHR gene mutation, transmitted as an
      autosomal recessive trait. The propositus presented with primary amenorrhea and
      absent thelarche and pubarche. Dynamic tests demonstrated absent spontaneous
      gonadotropin pulsatility, and no response to either exogenous pulsatile (10
      microg/pulse at 90-min intervals over 6 h) or acute (100 microg) GnRH
      administration. However, she responded to exogenous gonadotropin administration,
      with a resulting normal pregnancy. Genomic DNA extracted from peripheral blood
      was PCR amplified using amplimers spanning intron-exon boundaries for the three
      exons of GnRHR and revealed a homozygous splice junction mutation (G to A
      transversion) at the intron 1-exon 2 boundary. Her unaffected sister, with a
      totally normal phenotype, was heterozygous for this mutation. After lymphocyte
      Epstein-Barr virus transformation, RNA was extracted and subjected to RT-PCR,
      using primers located in the first and third exons. Results showed a transcript
      lacking all of exon 2 (exon 2 skipping), with splicing of exon 1 to exon 3. This
      created a frame shift, generating a coding sequence for three new amino acids,
      followed by a stop codon. Although it is not clear whether the mutant receptor is
      actually expressed, the resultant mRNA sequence was presumed to produce a
      truncated receptor with no binding or signaling capacity.

PMID- 12050283
TI  - Free and total insulin-like growth factor (IGF)-I levels decline during fasting:
      relationships with insulin and IGF-binding protein-1.
AB  - We have previously demonstrated that IGF-binding protein-1 (IGFBP-1) levels rise
      steadily during fasting, following an inverse relationship with insulin. The
      function of the IGFBP-1 rise is unknown, but it has been hypothesized that IGFBP
      1 serves as a glucose counterregulatory hormone during fasting and hypoglycemia
      by binding free IGFs, thus inhibiting IGF interactions with IGF receptors. Our
      objective in this study was to determine levels of free and total IGFs during
      fasting together with their interrelationships with simultaneous IGFBP-1,
      insulin, and glucose levels. Our patient population consisted of 22 children,
      aged 6 months to 15 yr, who underwent diagnostic fasting studies in the General
      Clinical Research Center. Blood was sampled at baseline and at 6-h intervals for
      glucose, IGFBP-1, free and total IGF-I, and insulin. The fasting studies lasted
      14-40 h and were terminated at a glucose concentration of less than 50 mg/dl (n =
      11) or for the completion of the allotted fasting duration (n = 11). Of the
      children studied, 11 had ketotic hypoglycemia, 8 had no disorder, 2 had steroid
      induced adrenal suppression, and 1 had recovered transient hyperinsulinism.
      During fasting, IGFBP-1 levels rose above mean initial levels of 27.1 +/- 13.4
      ng/ml to a mean of 318.4 +/- 29.9 ng/ml at the end point (P < 0.001). Insulin
      levels declined from a mean initial level of 7.4 +/- 1.3 mU/ml to a mean level of
      1.4 +/- 0.4 mU/ml at the end point (P < 0.001). Concomitantly, free and total IGF
      I levels declined from initial levels of 0.48 +/- 0.08 and 180.3+/- 27 ng/ml,
      respectively, to mean levels of 0.10 +/- 0.02 ng/ml (P < 0.001) and 119.3 +/- 22
      ng/ml (P = 0.001), respectively, at the end point. Levels of free IGF-I were
      inversely associated with IGFBP-1 over the course of fasting (P = 0.002).
      Similarly, total IGF-I was negatively associated with IGFBP-1 (P = 0.01). We
      conclude that free and total IGF-I levels decline steadily over the course of
      fasting. This decline in free IGF-I appears to be the result of the steady rise
      in IGFBP-1 that occurs as insulin declines. We speculate that the decline in IGF
      levels, controlled by the rise in IGFBP-1, serves to protect against possible
      insulin-like activity of the IGFs during fasting.

PMID- 12050284
TI  - Food fails to suppress ghrelin levels in obese humans.
AB  - Ghrelin is the first circulating hormone shown to stimulate feeding in humans
      following systemic administration. Food consumption decreases circulating ghrelin
      concentrations in lean subjects but the effects of feeding have not been studied
      in the obese. METHODS: We investigated the effects of a test meal on plasma
      ghrelin and leptin concentrations in 13 lean and 10 obese subjects. RESULTS:
      Fasting ghrelin was significantly higher in lean than in obese subjects (857
      pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating
      in the lean group before returning rapidly towards baseline values: (p = 0.003).
      There was no change in circulating ghrelin in the obese group. Circulating leptin
      concentration also fell acutely 15 minutes following food intake in lean but not
      obese subjects (p < 0.0001). CONCLUSIONS: Obese subjects do not exhibit the
      decline in plasma ghrelin and leptin seen after a meal in the lean. The role of
      the decline in leptin is unclear but given the orexigenic properties of ghrelin,
      the lack of suppression following a meal in obese subjects could lead to
      increased food consumption and suggest that ghrelin may be involved in the
      pathophysiology of obesity.

PMID- 12050285
TI  - The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS
      R, in humans.
AB  - Ghrelin is a novel growth hormone-releasing peptide, originally identified in the
      rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor
      (GHS-R1a). Ghrelin is involved in the regulation of GH release, but it has
      recently been suggested that ghrelin may have other actions, including effects on
      appetite, carbohydrate metabolism, heart, kidney, pancreas, gonads, and cell
      proliferation. The distribution of ghrelin, its functional receptor (type 1a) and
      the unspliced, non-functional GHS-R type 1b mRNA expression was investigated in
      various human tissues using classical and real-time reverse transcription and
      polymerase chain reaction. GHS-R1a was predominantly expressed in the pituitary
      and at much lower levels in the thyroid gland, pancreas, spleen, myocardium and
      adrenal gland. In contrast, ghrelin was found in the stomach, other parts of the
      gut and, indeed, in all the tissues studied (adrenal gland, atrium, breast,
      buccal mucosa, esophagus, Fallopian tube, fat tissue, gall bladder, human
      lymphocytes, ileum, kidney, left colon, liver, lung, lymph node, muscle, muscle,
      myocardium, ovary, pancreas, pituitary, placenta, prostate, right colon, skin,
      spleen, testis, thyroid, and vein). GHS-R1b expression was also widespread in all
      tissues studied. The significance of the widespread tissue distribution of
      ghrelin remains to be determined. These data suggest that ghrelin might have
      widespread physiological effects via different, partly unidentified, subtypes of
      the GHS-R in endocrine and non-endocrine tissues.

PMID- 12050287
TI  - Expression of multiple corticotropin-releasing hormone receptors in the human
      heart.

PMID- 12050289
TI  - Serum cortisol and 17-hydroxyprogesterone concentrations in children with classic
      congenital adrenal hyperplasia.

PMID- 12050290
TI  - Occurrence of pheochromocytoma in a MEN2A family with codon 609 mutation of the
      RET proto-oncogene.

PMID- 12050291
TI  - TSH receptor expression in cardiac muscle tissue.

PMID- 12050292
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 12050293
TI  - National Hormone & Peptide Program--NIDDK: recombinant hormones, hypothalamic
      peptides & other hormones, antisera, reagents, & hormone assay services
      available.

PMID- 12050294
TI  - Strategic initiatives in interventional radiology: a new vision.

PMID- 12050295
TI  - Surgical and endovascular treatment of lower extremity venous insufficiency.
AB  - Lower extremity venous insufficiency is a highly prevalent condition. Now it is
      understood that telangiectasias, reticular varicosities, and true varicose veins
      are physiologically similar and etiologically identical. The four main influences
      causing these abnormalities are heredity, female sex, gravitational hydrostatic
      forces, and hemodynamic muscular compartment pressure. There are clear
      indications and goals for intervention. A cornerstone in the treatment of venous
      insufficiency is elimination of sources of venous hypertension. One of these is
      the refluxing greater saphenous vein. Minimally invasive saphenous ablation can
      be achieved by radiofrequency energy and laser light energy. These new techniques
      eliminate the psychologic barrier to treatment caused by the term "stripping" and
      allow the objectives of surgery to be achieved with minimal invasion and quick
      recovery. Endovenous techniques show great promise. They provide minimal
      invasion, often under local anesthesia and intravenous sedation, thereby
      eliminating the need for general anesthesia. Objectives of venous insufficiency
      have been established and the endoluminal minimally invasive techniques developed
      in recent years appear to accomplish their goals.

PMID- 12050296
TI  - Endovenous obliteration with radiofrequency-resistive heating for greater
      saphenous vein insufficiency: a feasibility study.
AB  - PURPOSE: To assess the feasibility, safety, and clinical utility of ultrasound
      (US)- and fluoroscopy-guided endovenous saphenous vein obliteration with
      radiofrequency (RF)-resistive heating in the treatment of primary venous
      insufficiency. MATERIALS AND METHODS: Thirty legs of 27 patients with mild to
      moderate varicose veins and primary greater saphenous vein (GSV) insufficiency
      diagnosed with duplex US were treated. An endovenous catheter was inserted via US
      guided percutaneous puncture or a skin incision. Fluoroscopy and US were used to
      locate the electrodes at the saphenofemoral junction. GSVs were occluded with RF
      resistive heating. Local phlebectomies or sclerotherapy were performed in all
      procedures to treat varicose veins and teleangiectases. Persistence of vein
      occlusion and complications potentially attributable to endovenous treatment were
      assessed at 1 week, 6 weeks, 3 months, 6 months, and 1 year. RESULTS: The mean
      follow-up time was 9.6 months (SD, 3.8 mo). By the time of the last follow-up
      visit, occlusion of the treated segment of the GSV had been achieved in 22 legs
      (73.3%). Persisting patency or recanalization of the GSV was detected in eight
      legs (26.7%). One patient (3.3%) had varicosity-related symptoms, and three
      treated legs (10%) had recurrent or new varicosities. Postoperative complications
      included saphenous nerve paresthesia in three legs (10%) and thermal skin injury
      in one limb (3.3%). CONCLUSION: Endovenous obliteration employing RF-resistive
      heating is a relatively safe and promising minimally invasive technique for the
      treatment of primary GSV insufficiency.

PMID- 12050297
TI  - Catheter-directed thrombolysis in deep venous thrombosis with use of reteplase:
      immediate results and complications from a pilot study.
AB  - PURPOSE: To prospectively determine the thrombolytic success and complication
      rates of catheter-directed thrombolytic infusions in deep vein thrombosis (DVT)
      with use of reteplase. MATERIALS AND METHODS: After approval by the institutional
      review board, prospective, detailed data were obtained for 25 consecutive
      patients with acute and chronic DVT of the upper or lower extremity (seven upper
      extremity; 14 lower extremity; four vena cava). Infusion rates were 1.0 U/h in
      five patients and 0.5 U/h in the remaining 20. Subtherapeutic heparin doses of
      300-400 U/h were administered. Thrombolytic success was defined as 95%
      thrombolysis with return of antegrade flow. Data, including complications such as
      bleeding, need for transfusions, and laboratory values (fibrinogen, platelets,
      hematocrit, hemoglobin, and prothrombin time) were obtained throughout the
      infusions. RESULTS: The total dose of reteplase administered ranged from 2.5 to
      42 U (median, 16.5 U). The total infusion time ranged from 0.3 to 84 hours
      (median, 29 h). Thrombolytic success was achieved in 92% of patients.
      Endovascular stent placement and/or percutaneous transluminal angioplasty were
      required in 52% of patients to ensure maintenance of patency. Pre- and
      postprocedural average fibrinogen levels were 340 mg/dL and 315.3 mg/dL,
      respectively. The lowest mean fibrinogen levels for the two dose groups were
      265.86 mg/dL for the 0.5 U/h group and 314.18 mg/dL for the 1.0 U/h group. The
      lowest fibrinogen level during the procedure was 252.3 mg/dL (range, 35 to >700).
      There were only two instances of fibrinogen levels that decreased to below 90
      mg/dL: 35 mg/dL and 43 mg/dL. Thrombolytic failures occurred in two patients: one
      with acquired immune deficiency syndrome in a hypercoagulable state and one with
      a major bleeding complication. This was the only patient with a bleeding
      complication (4%). Hemorrhage occurred from the site of a previous mediastinal
      biopsy-which should have rendered her ineligible for the study-performed 18 hours
      before the thrombolysis. If thrombolysis had not been attempted in this patient,
      the complication rate would have been 0%. CONCLUSION: Although there are reports
      of thrombolytic therapy in peripheral vascular occlusive disease, this study is
      one of the first to evaluate thrombolytic drugs in the deep venous system
      exclusively. Reteplase was found to be effective in the thrombolytic treatment of
      acute and chronic DVT.

PMID- 12050298
TI  - New ePTFE/FEP-covered stent in the palliative treatment of malignant biliary
      obstruction.
AB  - PURPOSE: To determine the technical efficacy and safety of an expanded
      polytetrafluoroethylene and fluorinated ethylene propylene (ePTFE/FEP)-covered
      metallic stent in the management of malignant biliary obstruction and to evaluate
      its clinical efficacy by estimating stent patency and patient survival rates.
      MATERIALS AND METHODS: Twenty-six patients with common bile duct stricture caused
      by malignant disease were treated by placement of 29 stents. The stent consists
      of an inner ePTFE/FEP lining and an outer supporting structure of nitinol wire.
      Multiple wire sections elevated from the external surface provide anchoring.
      Stents are available in two versions, with or without holes in the proximal stent
      lining. Holes should provide drainage of the cystic duct or biliary side branches
      when covered by the proximal stent end. Clinical evaluation and assessment of
      serum bilirubin and liver enzyme levels were done before stent placement and at
      1, 3, 6, and 9 months. Average follow-up duration was 5.4 months (range, 5 d to
      12.5 mo). RESULTS: Placement was successful in all cases. The 30-day mortality
      rate was 11.5%. The survival rates were 40% and 15% at 6 and 12 months,
      respectively. Eighty-four percent of patients had adequate palliative drainage
      during their lifetime. The stent patency rates were 91%, 77%, and 77% at 3, 6,
      and 12 months, respectively. Four patients (16%) presented with stent occlusion
      and needed repeat intervention. No migration occurred. Complications other than
      stent occlusion occurred in five patients (19%); among these, acute cholecystitis
      was observed in three patients (12%). CONCLUSION: Preliminary results suggest
      that placement of this ePTFE/FEP-covered stent is feasible and effective in
      achieving biliary drainage. The percentage of patients undergoing lifetime
      palliation and the midterm patency are promising. However, the incidence of acute
      cholecystitis is high. Treatment of a larger group of patients is mandatory to
      validate these long-term results.

PMID- 12050299
TI  - Endovascular treatment of hepatic venous outflow obstruction after living-donor
      liver transplantation.
AB  - PURPOSE: To evaluate the effectiveness and safety of percutaneous interventional
      management of hepatic venous outflow obstruction after living-donor liver
      transplantation (LDLT). MATERIALS AND METHODS: Percutaneous balloon angioplasty
      (n = 5) and stent placement (n = 22) were attempted in 27 patients with hepatic
      venous outflow obstruction. Patient follow-up included clinical and laboratory
      data collection, Doppler ultrasonography (US), hepatic venography, and computed
      tomography. The following parameters were documented retrospectively: technical
      success and complications, clinical improvement, and recurrence. Technical
      success was defined as elimination or successful reduction of pressure gradients
      across the stenosis and clinical success was defined as amelioration of
      presenting signs. Recurrence was defined as relapse of clinical signs with
      hepatic venous anastomotic restenosis on Doppler US. RESULTS: Technical success
      was achieved in all patients. The mean pressure gradients across the stenoses
      before and after the procedure were 10.6 mm Hg +/- 6.4 (range, 3-39 mm Hg) and
      2.4 mm Hg +/- 2.6 (range, 0-8 mm Hg), respectively (P < .001). Three of the five
      patients who underwent balloon angioplasty developed recurrent stenosis 1-5 weeks
      after the procedure. These patients underwent repeat balloon angioplasty, and two
      of them eventually underwent stent placement (n = 1) or surgical repositioning (n
      = 1) of the graft. Three of the 22 patients who underwent stent placement
      required a second stent placement procedure because of malpositioning, partial
      migration, and acute angulation. During the mean follow-up period of 49 weeks +/-
      47 (range, 3-214 wk), clinical success was achieved in 20 of 27 patients (73%).
      CONCLUSION: Percutaneous interventional management is an effective and safe
      adjunct for the treatment of hepatic venous outflow obstruction after LDLT.

PMID- 12050300
TI  - Biologic fixation of polyester- versus polyurethane-covered stents in a porcine
      model.
AB  - PURPOSE: Migration of endoprostheses remains a concern in endovascular aneurysm
      treatment. Biologic fixation is supposed to enhance anchorage, but the diseased
      atherosclerotic aorta in humans has demonstrated a limited capacity to
      incorporate an endoprosthesis by cellular proliferation. The biologic response of
      two different types of endoprostheses was evaluated in the porcine aorta.
      MATERIALS AND METHODS: Two types of endoprostheses--four polyurethane-covered
      (PUC) stents with a macroporous polyurethane covering and four polyester-covered
      (PEC) stents with a woven polyester covering--were implanted in eight infrarenal
      porcine aortas for 6 weeks. Electron microscopy and qualitative and quantitative
      microscopy were performed on serial cross sections. RESULTS: The PUC stents
      demonstrated an increase in diameter (from 8 mm +/- 1 to 10 mm +/- 1, 12.5%; P =
      .009), whereas the PEC stents persisted in their original dimensions (8 mm +/- 1,
      0%). PUC and PEC stents were covered by continuous thrombus-free neointima (269
      microm +/- 51 vs 575 microm +/- 113, respectively; P < .01). The PUC stents
      demonstrated firm attachment to the aorta as a consequence of a granulation
      tissue with ingrowth into the pores of the polyurethane covering. The PEC stents
      remained in loose contact with the aorta in the absence of tissue ingrowth.
      CONCLUSIONS: Enhanced biologic fixation was achieved by extensive granulation
      tissue invading the pores of PUC endoprostheses. This finding can modify the
      design of future devices.

PMID- 12050301
TI  - Lack of suitability of the rabbit model for particulate uterine artery
      embolization.
AB  - PURPOSE: The goal of this study was to evaluate the rabbit model for studies of
      particulate uterine artery embolization (UAE). Rabbits were chosen because it was
      believed that their year-round breeding time and short duration of pregnancy
      would be useful in studies of fertility and pregnancy after UAE. MATERIALS AND
      METHODS: Bilateral UAE was performed in 12 adult female New Zealand White rabbits
      weighing 4-5.2 kg. All animals were proven to be breeders before treatment. Each
      uterine artery was embolized to stasis with use of 180-300- microm polyvinyl
      alcohol (PVA) particles (n = 9 animals), 500-710- microm PVA particles (n = 1),
      or tris-acryl 500-700- microm gelatin microspheres (n = 2). RESULTS: Two rabbits
      died 7 days after embolization and the other 10 rabbits had to be killed because
      of malaise and weight loss 4-8 d after embolization. In all animals, necropsy
      demonstrated extensive uterine necrosis sparing only the tip of the uterine horn.
      CONCLUSION: Rabbits are an unsuitable model for studies of UAE with the embolic
      agents in clinical use.

PMID- 12050303
TI  - Stent placement in four patients with hepatic artery stenosis or thrombosis after
      liver transplantation.
AB  - Hepatic artery stenosis and thrombosis represent dangerous complications of liver
      transplantation because the associated mortality and morbidity rates are high. In
      the past, repeat transplantation was considered the first-choice therapy;
      however, new surgical and interventional revascularization techniques have been
      suggested recently. Although extensive experience has been acquired with
      percutaneous transluminal angioplasty (PTA) and fibrinolysis techniques, only
      sporadic cases of stent placement in the hepatic artery of a transplanted liver
      have been reported, and no long-term results of this technique are available. In
      this study, seven stents (five Wallstents and two Palmaz stents) were positioned
      in four patients (two with stenoses and two with thromboses). Stent placement was
      performed in three cases after PTA and fibrinolysis, whereas primary stent
      placement was performed in the fourth. In all cases, technical success was
      achieved. During 18-25 months of follow-up, all stents proved patent and no
      patient required another transplantation. Although experience is still limited,
      the authors' experience indicates that placement of a stent in the hepatic artery
      in cases of stenosis or thrombosis yields good medium-term success, improving the
      results obtained by fibrinolysis and PTA and consequently enabling the graft to
      survive and avoiding the need for repeat transplantation.

PMID- 12050302
TI  - Real-time MR properties of particulate embolic agents tested in a dynamic flow
      model.
AB  - PURPOSE: Interventional magnetic resonance (MR)-guided transcatheter embolization
      could potentially limit radiation exposure and improve visualization of target
      organs. The feasibility of monitoring injection and distribution of embolic
      agents was assessed in a dynamic flow model with real-time MR imaging. MATERIALS
      AND METHODS: MR-compatible flow models were constructed with use of clear plastic
      chambers containing 170-microm polyethylene tubular filters. Gadolinium (Gd)
      impregnated polyvinyl alcohol (PVA) particles (355-500 and 500-710 microm in
      size) and Gd-impregnated microspheres (Embospheres, 300-500 and 500-700 microm in
      size) were injected into the flow circuit under real-time dynamic T1-weighted
      fast field echo guidance at four images per second. A dynamic steady-state free
      precession sequence at four images per second was used to monitor the injection
      of unmodified Embo-Gold 700-900- microm particles. High-resolution scans were
      obtained before and after each particle injection. RESULTS: MR signal enhancement
      on the dynamic T1-weighted fast field echo sequence was visible during the
      injection of Gd-impregnated microspheres. Gd-impregnated PVA particles were not
      detected by this sequence. After injection, microsphere and PVA localization to
      the filter chambers was confirmed by the high-resolution scans. On the high
      resolution sequences, relative MR signal enhancement of the microspheres was
      higher than that of the PVA particles. The Embo-Gold particles were minimally
      detectable on the dynamic sequence and undetectable by the high-resolution scan.
      After particle injection, direct inspection of the filter chamber showed trapping
      of all particle types and sizes. CONCLUSION: Real-time MR tracking of Gd
      impregnated embolic agents is possible in vitro.

PMID- 12050304
TI  - Endovascular repair of thoracic aortic aneurysm and intramural hematoma in giant
      cell arteritis.
AB  - An 80-year-old woman with established giant cell arteritis presented at the
      authors' institution with a 6.5-cm false aneurysm of the descending thoracic
      aorta complicated by focal dissection and intramural hematoma after a 1-week
      history of acute-onset chest pain. The patient underwent uncomplicated
      endovascular aortic repair with a 32-mm x 15-cm TagExcluder stent-graft. After
      the procedure, the intramural hematoma resolved and the patient's corticosteroid
      and immunosuppressive therapy was repeatedly adjusted. However, the giant cell
      arteritis activity relapsed after 8 months with development of a similar 1.5-cm
      false aneurysm below the thoracic stent-graft, complicated by focal intramural
      hematoma. Repeat uncomplicated thoracic stent-graft implantation was performed
      and CT follow-up displayed resorption of the intramural hematomas with no
      evidence of endoleak or any new aortic pathology. This report discusses the
      difficult management of patients with relapsing active aortic giant cell
      arteritis and the potential role for endovascular thoracic aortic repair.

PMID- 12050305
TI  - Treatment of splenic artery aneurysm with use of a stent-graft.

PMID- 12050306
TI  - Mesenteric arteriographic findings in a patient with strongyloides stercoralis
      hyperinfection.
AB  - The authors present a case of a Latin American patient with systemic lupus
      erythematosus who was referred for a mesenteric arteriogram because of acute
      lower gastrointestinal bleeding. Multiple segments of dilation alternating with
      stenosis or spasm were noted in the superior mesenteric artery/inferior
      mesenteric artery distributions. At the time, these irregularities were thought
      to be representative of lupus vasculitis. Despite appropriate treatment for
      vasculitis, the patient continued to have bleeding episodes and ultimately died
      of multiple organ failure. Autopsy demonstrated no evidence of vasculitis, but
      did demonstrate the unexpected finding of Strongyloides stercoralis
      hyperinfection with vessel invasion.

PMID- 12050307
TI  - SCVIR 2002 film panel case 5: traumatic injury to the circumflex humeral artery.

PMID- 12050308
TI  - SCVIR 2002 film panel case 6: hematuria caused by ureteroarterial fistula.

PMID- 12050309
TI  - SCVIR 2002 film panel case 7: biliary obstruction secondary to a choledochal
      cyst.

PMID- 12050310
TI  - SCVIR 2002 film panel case 8: hemoptysis caused by a pulmonary venous aneurysm.

PMID- 12050311
TI  - Re: sheathless technique of ash split-cath insertion.

PMID- 12050313
TI  - Salvage of a misplaced hickman catheter: a new endovascular technique.

PMID- 12050314
TI  - Computer-aided intrapatient comparison of brain SPECT images: the gray-level
      normalization issue applied to children with epilepsy.
AB  - A tool was developed for automated intrapatient comparison of brain SPECT images,
      with specific emphasis on gray-level normalization. METHODS: Ictal and interictal
      (99m)Tc-ethyl cysteinate dimer SPECT images were acquired for 6 children with
      partial epilepsy (age range, 2-10 y). For each patient, 3-dimensional rigid
      geometric ictal-to-interictal image registration optimizing different classic
      criteria (correlation coefficient, ratio uniformity) in a multiscale translation
      rotation 6-parameter space was first performed. Gray-level normalization was then
      performed with different methods, using a 1- or 2-parameter linear model. In the
      1-parameter case, the scaling factor was equal to the interictal-to-ictal ratio
      of the maximum, mean, or median values calculated within different reference
      volumes (whole brain or cerebellum) or obtained by linear regression between
      ictal and interictal counts in the brain or by maximizing a robust criterion, the
      number of deterministic sign changes in the subtraction images. In the 2
      parameter case, the scaling factor and additive constant were estimated using
      these last 2 methods. For each patient, registration validity and normalization
      plausibility were assessed by considering the correlation scatterplot together
      with the different normalization lines and by comparing interictal and registered
      normalized ictal images using a twin display (with isocontours) in the 3
      orthogonal planes. Three-dimensional volumes of interest could be selected on
      coupled interictal-subtraction images for further focused numeric comparison.
      RESULTS: After a satisfactory and stable geometric registration with both
      criteria, the different normalization methods led to similar subtraction images
      for 5 of 6 patients, except the maxima ratio, which gave noticeably different
      results in 2 patients. For the remaining patient, with highly dissimilar ictal
      interictal images, the maxima ratio normalization was obviously wrong and the
      other 1-parameter methods probably better depicted the data than did the 2
      parameter methods. CONCLUSION: When comparing intrapatient brain SPECT images,
      one should be aware of the potential impact of the gray-level normalization
      method on clinical interpretation. For ictal-interictal images, simple robust
      scaling should be recommended. In particular, image maximum should generally not
      be considered a valid reference, and no additive constant is needed in the linear
      gray-level normalization model.

PMID- 12050315
TI  - Changes in regional cerebral blood flow caused by deep-brain stimulation of the
      subthalamic nucleus in Parkinson's disease.
AB  - The aim of this study was to investigate the effect of deep-brain stimulation of
      the subthalamic nucleus (STN) on regional cerebral blood flow (rCBF) throughout
      the entire brain volume in patients with Parkinson's disease and to evaluate
      which of the brain areas showing an rCBF increase during STN stimulation related
      significantly to the improvement in motor function. METHODS: Ten consecutive
      Parkinson's disease patients (6 men, 4 women; mean age +/- SD, 59 +/- 8 y) with
      bilateral STN stimulators underwent 3 rCBF SPECT examinations at rest: the first
      preoperatively and the second and third postoperatively (follow-up, 4.8 +/- 1.4
      mo) with STN stimulators on and off, respectively. The motor unified Parkinson's
      disease rating scale, the Hoehn and Yahr disability scale, and the Schwab and
      England activities-of-daily-living scale were used to evaluate the clinical state
      under each condition. Statistical parametric mapping was used to investigate rCBF
      during STN stimulation in comparison with rCBF preoperatively and with STN
      stimulators off. Also evaluated with statistical parametric mapping was the
      relationship between rCBF and individual motor scores used as covariates of
      interest. RESULTS: STN stimulation significantly changed rCBF in the right pre
      supplementary motor area (pre-SMA), anterior cingulate cortex, and dorsolateral
      prefrontal cortex and in the medial Brodmann's area 8 (BA8) as defined in the
      atlas of Talairach and Tournoux (P < 0.05 corrected for multiple comparisons).
      The rCBF in these areas increased from the preoperative condition to the
      stimulators-on condition and decreased again after the stimulators were switched
      off. A significant correlation was detected between the improvement in motor
      scores and the rCBF increase only in the right pre-SMA and in the anterior
      cingulate motor area (P < 0.005, uncorrected). CONCLUSION: According to the
      topographic organization of the primate STN, our study shows that stimulation of
      the STN leads to rCBF increases in the motor (pre-SMA), associative, and limbic
      territories (anterior cingulate) in the frontal cortex. The significant
      correlation between motor improvement and rCBF increase in the pre-SMA and the
      anterior cingulate motor area reinforces the hypothesis that STN stimulation in
      parkinsonian patients can potentiate the cortical areas participating in higher
      order aspects of motor control.

PMID- 12050316
TI  - Perfusion SPECT changes after acute and chronic vagus nerve stimulation in
      relation to prestimulus condition and long-term clinical efficacy.
AB  - Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients
      with refractory epilepsy. Previous studies have implicated thalamic and mesial
      temporal involvement in acute stimulation. In this study, acute and chronic
      effects of VNS in patients with refractory complex partial seizures with or
      without secondary generalization (CPS +/- SG) were evaluated with respect to the
      prestimulus condition and long-term follow-up. METHODS: Twenty-three patients (12
      females, 11 males; mean age, 32.4 +/- 10.6 y; mean CPS +/- SG duration, 21.0 +/-
      11.7 y) were prospectively included. All patients were considered unsuitable
      candidates for resective surgery because of nonlocalizing findings in the
      presurgical evaluation. All underwent a split-dose (99m)Tc-ethyl cysteinate dimer
      activation study before and immediately after their initial stimulation (0.25 or
      0.5 mA, 30 Hz) on a high-resolution triple-head gamma camera. Ten patients also
      underwent a SPECT activation study 5.7 +/- 1.6 mo after implantation with an
      additional 0.25-mA stimulus superposed on a therapeutic intensity of 1.5 +/- 0.3
      mA. Data were analyzed by an automated semiquantitative volume-of-interest
      analysis after stereotactic anatomic standardization. RESULTS: In the acute,
      initial setting, the left thalamus, right parahippocampal gyrus, and right
      hippocampus were deactivated by VNS (P < 0.011). Acute stimulation in the chronic
      state resulted in a significant left thalamic activation (P < 0.001). When
      chronic perfusion was compared with the initial pre-VNS baseline, perfusion
      decreases were found in both thalami (-5.3% on the left and -3.4% on the right, P
      < or = 0.04). Perfusion changes in chronic VNS correlated negatively with the
      prestimulus perfusion pattern, indicating the tendency toward decreased brain
      activity on VNS. Initial stimulation changes in the right amygdala in the group
      of 10 patients with chronic assessment were predictive of therapeutic response (P
      = 0.018); in addition, right chronic hippocampal perfusion changes correlated
      strongly with the long-term clinical efficacy of VNS (P = 0.004). CONCLUSION:
      Under initial and chronic conditions, acute VNS stimulation produces different
      perfusion changes that are related to the interictal perfusion pattern before
      stimulation. The long-term mechanism of clinically effective VNS may rely on
      mainly hippocampal/amygdala and thalamic inhibition. Acute amygdala and chronic
      hippocampal perfusion changes are predictive of long-term therapeutic response in
      specific patient subgroups.

PMID- 12050317
TI  - Prognostic value of (99m)Tc-sestamibi washout in predicting response of locally
      advanced breast cancer to neoadjuvant chemotherapy.
AB  - This study evaluated the role of (99m)Tc-sestamibi washout in the prediction of
      pathologic tumor response to neoadjuvant chemotherapy in 30 patients with locally
      advanced breast cancer. METHODS: Two (99m)Tc-sestamibi studies were performed
      before and after chemotherapy for each patient. Early (10 min) and delayed (240
      min) planar breast views were acquired after a 740-MBq (99m)Tc-sestamibi
      intravenous injection, and the washout rate (WOR) was computed. All patients
      underwent radical mastectomy with pathologic evaluation of the residual tumor
      size. RESULTS: The pretherapy (99m)Tc-sestamibi WOR ranged from 14% to 92% (mean
      +/- SD, 50% +/- 18%). At pathologic examination, 15 patients showed no tumor
      response to chemotherapy and 15 patients showed an objective response to
      chemotherapy. The pretherapy (99m)Tc-sestamibi study predicted chemoresistance
      (WOR > 45%) in 18 of 30 patients and no chemoresistance (WOR < or = 45%) in 12 of
      30 patients. When the WOR cutoff was set at >45%, the prognostic performance of
      the test was indicated by a sensitivity of 100%; a specificity of 80%; positive
      and negative predictive values of 83% and 100%, respectively; and a likelihood
      ratio of 5. The repeatability of the test was good, with 80%-93% interreader
      agreement (kappa = 0.57-0.85). Posttherapy (99m)Tc-sestamibi studies confirmed
      the pretherapy study prediction in 29 of 30 patients. CONCLUSION: (99m)Tc
      Sestamibi WOR is a reliable test for predicting tumor response to neoadjuvant
      chemotherapy. In fact, negative findings (WOR < or = 45%) rule out
      chemoresistance and positive findings (WOR > 45%) indicate a high risk of
      chemoresistance.

PMID- 12050319
TI  - Quantitative analysis of lung perfusion in patients with primary pulmonary
      hypertension.
AB  - The aim of this study was to evaluate quantitatively the heterogeneity of lung
      perfusion scans in patients with primary pulmonary hypertension (PPH) and to
      compare it with the severity of disease. METHODS: Lung perfusion scans were
      obtained on 22 patients with PPH and 12 age-matched control subjects. The
      perfused area rates (PARs) were calculated by dividing the lung area in each 10%
      threshold width from 10% to 100% of maximal counts by total lung area. The total
      absolute difference in the PAR between each patient and the mean control value
      was assumed as the perfusion index of the lung (P index). The P index was
      compared with hemodynamic parameters and the right ventricular ejection fraction
      (RVEF), including 7 patients who received long-term vasodilator therapy. RESULTS:
      The P index correlated significantly with mean pulmonary arterial pressure (P <
      0.001) and RVEF (P < 0.05). In patients with vasodilator therapy, the P index was
      improved significantly after therapy (P < 0.05) and was associated with a
      reduction in pulmonary arterial pressure. CONCLUSION: Quantitative assessment of
      lung perfusion irregularity might provide useful information about the severity
      of disease and the effect of therapy in addition to the routine visual
      representation.

PMID- 12050318
TI  - The impact of PET on the management of lung cancer: the referring physician's
      perspective.
AB  - (18)F-FDG PET is a molecular whole-body imaging modality that is increasingly
      being used for diagnosing, staging, and restaging cancer. The objective of this
      study was to determine referring physicians' perspectives on the impact of (18)F
      FDG PET on staging and management of lung cancer. METHODS: A questionnaire was
      sent to the 292 referring physicians of 744 consecutive patients with known or
      suspected lung cancer who were evaluated with PET. Questionnaires on 274 patients
      were returned (response rate, 37%). Management changes were categorized as
      intermodality (e.g., surgery to medical, surgery to radiation, and medical to no
      treatment) or intramodality (e.g., altered medical, surgical, or radiotherapy
      approach). RESULTS: The primary reasons for PET referral were staging of lung
      cancer in 61% of patients, diagnosis in 20%, and monitoring of therapy or the
      course of disease in 6%. Physicians reported that PET caused them to change their
      decision on clinical stage in 44% of all patients: The disease was upstaged in
      29% and downstaged in 15%. PET resulted in intermodality management changes in
      39% of patients, whereas 15% had an intramodality change. CONCLUSION: This survey
      based study of referring physicians suggests that PET has a major impact on
      staging and management of lung cancer.

PMID- 12050320
TI  - A Bayesian regression model for plasma clearance.
AB  - Nonlinear Bayesian regression permits curve fitting to a group of subjects
      simultaneously rather than individually. We evaluated this approach for
      interpreting plasma clearance curves with the goal of reducing curve-fitting
      failures and dealing objectively with problem datasets that may arise in clinical
      settings. METHODS: (99m)Tc-Diethylenetriaminepentaacetic acid plasma clearance
      curves from 79 subjects were analyzed. The data typically comprised 7-9 samples
      obtained from 5-10 to 180-240 min after injection. A 2-compartment model was
      fitted by Bayesian regression to yield compartmental hyperparameters V1, L21, and
      L12 corresponding to the volume of the compartment into which tracer was injected
      and the transfer rates from compartment 1 to compartment 2 and from compartment 2
      to compartment 1, respectively. This also yielded a clearance estimate for each
      subject. RESULTS: Estimated hyperparameters were V1 = 8.9 L, L21 = 0.026 min(-1),
      and L12 = 0.040 min(-1). Conventional methods led to fitting failures in 2 of the
      79 subjects but there were no failures with the Bayesian method. The
      hyperparameters were used to calculate the glomerular filtration rate for each
      subject from a single plasma sample with a root-mean-square error of 7.3 mL/min,
      which was not significantly different from the widely used Christensen-Groth
      formula. CONCLUSION: Fewer fitting failures were encountered than with
      conventional methods, offering an objective means of dealing with problem data.
      This conceptually simple model can be used directly to calculate clearance from a
      single plasma sample. It requires only the 3 parameters described above, whereas
      the Christensen-Groth method requires 6 parameters.

PMID- 12050321
TI  - Prognostic value of dobutamine-atropine stress (99m)Tc-tetrofosmin myocardial
      perfusion SPECT in patients with known or suspected coronary artery disease.
AB  - 99mTc-Tetrofosmin is a recently introduced radioactive isotope for the assessment
      of myocardial perfusion. Data regarding the prognostic value of stress imaging
      using this isotope are scarce. The aim of this study was to assess the prognostic
      value of dobutamine-atropine (99m)Tc-tetrofosmin SPECT for the prediction of late
      cardiac events in patients with known or suspected coronary artery disease.
      METHODS: A total of 721 consecutive patients with limited exercise capacity
      underwent dobutamine-atropine stress (99m)Tc-tetrofosmin SPECT. Follow-up was
      successful in 719 of 721 patients (99.7%). Twenty-eight patients who underwent
      early revascularization were excluded. RESULTS: Myocardial perfusion
      abnormalities were detected in 381 patients (55%) and included fixed defects in
      190 patients (27%) and reversible defects 191 patients (28%). During a mean
      follow-up period of 37 +/- 17 mo, there were 150 deaths (22%), of which 62 (41%)
      were attributed to cardiac causes. Nonfatal myocardial infarction occurred in 23
      patients (3%), and late (>3 mo) coronary revascularization was performed on 21
      patients (3%). The cardiac death rate was 1%/y in patients with a normal scan and
      5.1%/y in patients with an abnormal scan (P < 0.0001). In a multivariable Cox
      proportional-hazards model, the presence of abnormal perfusion was independently
      associated with an increased risk of cardiac death, after adjusting for clinical
      and stress test data (hazard ratio, 8.2; 95% confidence interval, 3.2-21).
      CONCLUSION: Dobutamine-atropine stress (99m)Tc-tetrofosmin SPECT is a useful
      imaging method for distinguishing patients at high and low risk of future cardiac
      events. The presence of perfusion abnormalities provides incremental prognostic
      information to clinical, stress electrocardiographic, and hemodynamic data.

PMID- 12050322
TI  - Exercise training in chronic heart failure: beneficial effects on cardiac (11)C
      hydroxyephedrine PET, autonomic nervous control, and ventricular repolarization.
AB  - Abnormalities of autonomic nervous function are associated with a poor prognosis
      of patients with chronic heart failure (CHF). We studied the effects of a 6-mo
      exercise training program on Q-T interval dispersion, heart rate and blood
      pressure variability, baroreflex sensitivity, myocardial blood flow (MBF), and
      presynaptic sympathetic innervation in 13 patients with New York Heart
      Association class II-III heart failure. METHODS: MBF was measured with the
      H(2)(15)O and C(15)O technique. Cardiac presynaptic innervation was studied by
      (11)C-hydroxyephedrine (HED) retention assessed with PET. Heart rate and blood
      pressure variability and baroreflex sensitivity were tested with the
      phenylephrine method. All studies were performed before and after a 6-mo exercise
      training program. The exercise capacity was determined by spiroergometry, and Q-T
      dispersion was measured from a standard 12-lead electrocardiogram. RESULTS: Q-T
      dispersion was reduced after the training period (mean +/- SEM, from 52 +/- 5 to
      36 +/- 5 ms [P = 0.01]). Global (11)C-HED retention improved from 0.228 +/- 0.099
      to 0.263 +/- 0.066 s(-1) (P < 0.05). Global MBF was not affected by training, but
      MBF increased in areas of low initial perfusion in patients with coronary artery
      disease (from 0.382 +/- 0.062 to 0.562 +/- 0.083 mL/g/min [P < 0.005]). The high
      frequency spectrum and total R-R interval variability increased (from 4.53 +/-
      0.30 to 5.02 +/- 0.36 ms(2) [P < 0.05] and from 3.60 +/- 0.34 to 4.31 +/- 0.37
      ms(2) [P < 0.005], respectively). Both changes correlated significantly with the
      observed change in (11)C-HED retention. There was a significant reduction of
      total and a near-significant reduction of low-frequency (LF) systolic blood
      pressure (SBP) variability (from 4.89 +/- 1.03 to 3.18 +/- 0.48 [P < 0.05] and
      from 2.79 +/- 0.38 to 1.76 +/- 0.24 [P = 0.059], respectively). The decrease in
      LF SBP variability correlated inversely with the enhancement of (11)C-HED
      retention (r = -0.66; P < 0.05). Baroreflex sensitivity increased from 5.83 +/-
      0.82 to 10.15 +/- 1.66 ms/mm Hg (P < 0.05). CONCLUSION: Exercise training induces
      beneficial changes in functional and imaging measures of cardiovascular autonomic
      nervous control. These observations point to a training-induced shift toward
      normalization of the compensatory autonomic nervous imbalance in CHF.

PMID- 12050323
TI  - Myocardial oxidative metabolism in remote normal regions in the left ventricles
      with remodeling after myocardial infarction: effect of beta-adrenoceptor
      blockers.
AB  - In patients with myocardial infarction (MI), an expansion of the remote normal
      regions of the left ventricle is often observed. However, the characteristics of
      such regions are not fully understood. Thus, we investigated this issue from the
      standpoint of myocardial oxidative metabolism using (11)C-acetate PET. METHODS:
      In 33 patients with recent MI (24 not receiving beta-blockers, 9 receiving beta
      blockers) and 12 age-matched normal control subjects, (11)C-acetate dynamic
      myocardial PET scanning was performed at rest. Time-activity curves of (11)C
      acetate in 5-7 regions of interest (ROIs) on the midventricular transaxial image
      in each subject were generated, and the clearance rate constant (K(mono)) in each
      ROI was calculated by monoexponential fitting as an index of myocardial oxidative
      metabolism. The left ventricular (LV) end-diastolic volume index as an index of
      LV remodeling and the heart rate. pressure product were obtained in all subjects.
      RESULTS: The LV end-diastolic volume index was significantly larger in patients
      with MI without beta-blockers than in normal control subjects (101 +/- 22.5 vs.
      61.6 +/- 12.8 mL x m(-2); P < 0.001). There was no significant difference in the
      heart rate x pressure product between the patients with MI without beta-blockers
      and the normal control subjects (8,229 +/- 1,503 vs. 8,311 +/- 1,311 mm Hg x min(
      1)). The K(mono) in remote normal regions was significantly greater in patients
      with MI without beta-blockers even when compared with the highest K(mono) on the
      anteroseptal wall of the left ventricle in normal control subjects (0.078 +/-
      0.022 vs. 0.065 +/- 0.007 min(-1); P < 0.01). In contrast, the heart rate.
      pressure product (6,911 +/- 1,135 mm Hg x min(-1)) and the K(mono) (0.054 +/-
      0.009 min(-1)) in remote normal regions were significantly less in patients with
      beta-blockers than in those without beta-blockers (P < 0.001). No significant
      difference in the LV end-diastolic volume index was found between the MI patients
      with and without beta-blockers. Multivariate regression analysis showed that beta
      blockers significantly and directly decreased the K(mono) in remote normal
      regions after adjusting the effect of the heart rate x pressure product, although
      the prime determinant of the K(mono) in such regions was the heart rate x
      pressure product. CONCLUSION: Myocardial oxidative metabolism in remote normal
      regions is accelerated in the left ventricles with remodeling after acute MI.
      Therapy using beta-blockers normalizes the myocardial oxidative metabolism in
      such regions through the reduction of the heart rate x pressure product and their
      direct effect on the myocardium.

PMID- 12050324
TI  - Calculation of the left ventricular ejection fraction without edge detection:
      application to small hearts.
AB  - Quantitative gated SPECT (QGS) software has been reported to overestimate the
      left ventricular ejection fraction (LVEF) in patients with small hearts. This
      finding is caused by the inaccurate detection of the endocardial surface of the
      left ventricle (LV) due to low resolution and partial-volume effects. In this
      article we develop a method to calculate the LVEF from gated SPECT data without
      edge detection and compare it with the QGS method of calculating the LVEF.
      METHODS: The short-axis images were transformed to the prolate spheroid
      coordinate system, and detection of the layer of maximum counts (a surface area
      of maximum counts) was made. First, the volume enclosed by the layer of maximum
      counts (V(max)) was calculated; then the corresponding ejection fraction
      [(LVEF)(max)] was calculated. The LVEF was calculated by multiplying the
      (LVEF)(max) by a constant factor, which was determined from a series of
      calculations made using QGS on larger hearts. In computer simulations the end
      diastolic left ventricular volume (EDV) and the targeted LVEF (tLVEF) were varied
      to produce LVs of different sizes. The LVs were modeled by 2 confocal
      hemiellipsoids with 7 different EDVs. The tLVEF was increased from 25% to 75%, in
      5% step-size increments, for a total of 11 different ejection fractions. These
      datasets were then smoothed, creating a total of 77 smoothed sets. The smoothed
      images were processed by the QGS method and by our method. In patient studies, 58
      patient datasets were processed by the QGS method and by our method. No
      attenuation correction was performed on these datasets. The patients were divided
      into 2 groups: 44 patients with large hearts (EDV > or = 80 mL) and 14 patients
      with small hearts (EDV < 80 mL). RESULTS: In computer simulations, the QGS method
      and our method performed well when imaging large EDVs (EDV > or = 80 mL). Our
      method derived better results than did the QGS method for small EDVs. In patient
      studies the LVEF calculated by our method matched well with the QGS LVEF in the
      44 patients with large hearts. The correlation coefficient between them was found
      to be 0.957. Of the 14 patients with small hearts, the LVEFs of 5 patients were
      severely overestimated by the QGS method compared with the results obtained with
      our method. CONCLUSION: It is possible to calculate the LVEF without edge
      detection. Compared with QGS LVEF, our method gave better results for small LVs
      in computer simulations.

PMID- 12050326
TI  - Sequential strategy using multimodality viability tests: does it work?

PMID- 12050325
TI  - Sequential (201)Tl imaging and dobutamine echocardiography to enhance accuracy of
      predicting improved left ventricular ejection fraction after revascularization.
AB  - 201Tl imaging and dobutamine echocardiography (DE) can both identify viable
      myocardium. Prediction of functional outcome after revascularization remains
      suboptimal with either technique because of the relatively low specificity of
      (201)Tl and low sensitivity of DE. This study was undertaken to develop an
      optimal testing strategy for prediction of post-revascularization functional
      outcome. METHODS: Seventy-three patients (mean [+/-SD] left ventricular ejection
      fraction [LVEF], 32% +/- 8%) underwent DE and resting (201)Tl SPECT (4-h delayed
      imaging) before surgical revascularization. Dysfunctional segments with (201)Tl
      activity > or = 50% or with contractile reserve were considered viable. LVEF was
      assessed before and 3-6 mo after revascularization. RESULTS: Analysis of receiver
      operator characteristic curves showed that the optimum criteria to predict
      improvement (> or = 5%) in LVEF after revascularization were > or = 6 viable
      dysfunctional segments (using a 16-segment model) on (201)Tl and > or = 4
      segments on DE. Sensitivity and specificity were 84% and 63% for (201)Tl (P <
      0.05 vs. DE) and 63% and 85% for DE (P < 0.05 vs. (201)Tl). Changing the (201)Tl
      criteria to improve specificity to 78% (> or = 8 segments) yielded a low
      sensitivity of 44%, and changing the DE criteria to improve sensitivity to 84% (>
      or = 2 segments) lowered specificity to 56%. Two sequential testing strategies
      were explored to achieve optimal sensitivity and specificity. In strategy 1, 33
      (45%) of 73 patients with an intermediate likelihood of viability by (201)Tl (5-8
      viable segments) underwent DE. In strategy 2, 31 (42%) of 73 patients with an
      intermediate likelihood of viability by DE (2-4 viable segments) underwent
      (201)Tl. For strategy 1, sensitivity did not change significantly (69%), whereas
      specificity was improved significantly (93%, P < 0.01 vs. (201)Tl). For strategy
      2, sensitivity improved significantly (78%, P < 0.05 vs. DE) and specificity
      remained unchanged (80%). CONCLUSION: Sequential testing by (201)Tl SPECT and DE
      in a subgroup of patients with an intermediate likelihood of viability by either
      test significantly enhanced prediction of post-revascularization improvement of
      LVEF.

PMID- 12050327
TI  - Measurement of ventricular volumes and function: a comparison of gated PET and
      cardiovascular magnetic resonance.
AB  - The aim of this study was to compare cardiac volume and function assessment using
      PET with the reference technique of cardiovascular magnetic resonance (CMR).
      METHODS: Left ventricular (LV) and right ventricular (RV) end-diastolic volume
      (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fractions (EF)
      were measured in 9 patients using both CMR and PET with inhaled C(15)O. RESULTS:
      Correlation between the techniques was generally reasonable (r values ranged from
      0.63 to 0.99). Best agreement was seen for ESV (LV and RV). With PET, there was a
      tendency to underestimate LV EF and EDV, and RV EDV and SV. Agreement was worst
      for LV SV. Percentage difference between CMR and PET measurements ranged from -2%
      to 15%; Bland-Altman limits of agreement ranged from 24% to 75%. CONCLUSION:
      Although small systematic differences exist, the agreement between PET and CMR
      suggests useful information regarding function, and volumes may be obtained from
      a standard PET protocol.

PMID- 12050328
TI  - Radioguided sentinel lymph node biopsy in malignant cutaneous melanoma.
AB  - The procedure of sentinel lymph node biopsy in patients with malignant cutaneous
      melanoma has evolved from the notion that the tumor drains in a logical way
      through the lymphatic system, from the first to subsequent levels. As a
      consequence, the first lymph node encountered (the sentinel node) will most
      likely be the first affected by metastasis; therefore, a negative sentinel node
      makes it highly unlikely that other nodes in the same lymphatic basin are
      affected. Although the long-term therapeutic benefit of the sentinel lymph node
      biopsy per se has not yet been ascertained, this procedure distinguishes patients
      without nodal metastases, who can avoid nodal basin dissection with its
      associated risk of lymphedema, from those with metastatic involvement, who may
      benefit from additional therapy. Sentinel lymph node biopsy would represent a
      significant advantage as a minimally invasive procedure, considering that an
      average of only 20% of melanoma patients with a Breslow thickness between 1.5 and
      4 mm harbor metastasis in their sentinel node and are therefore candidates for
      elective lymph node dissection. Furthermore, histologic sampling errors
      (amounting to approximately 12% of lymph nodes in the conventional routine) can
      be reduced if one assesses a single (sentinel) node extensively rather than
      assessing the standard few histologic sections in a high number of lymph nodes
      per patient. The cells from which cutaneous melanomas originate are located
      between the dermis and the epidermis, a zone that drains to the inner lymphatic
      network in the reticular dermis and, in turn, to larger collecting lymphatics in
      the subcutis. Therefore, the optimal route for interstitial administration of
      radiocolloids for lymphoscintigraphy and subsequent radioguided sentinel lymph
      node biopsy is intradermal or subdermal injection. (99m)Tc-Labeled colloids in
      various size ranges are equally adequate for radioguided sentinel lymph node
      biopsy in patients with cutaneous melanoma, depending on local experience and
      availability. For melanomas along the midline of the head, neck, and trunk,
      particular consideration should be given to ambiguous lymphatic drainage, which
      frequently requires interstitial administration virtually all around the tumor or
      surgical scar from prior excision of the melanoma. Lymphoscintigraphy is an
      essential part of radioguided sentinel lymph node biopsy because images are used
      to direct the surgeon to the sites of the nodes. The sentinel lymph node should
      have a significantly higher count than that of the background (at least 10:1
      intraoperatively). After removal of the sentinel node, the surgical bed must be
      reexamined to ensure that all radioactive sites are identified and removed for
      analysis. Virtually the entire sentinel lymph node should be processed for
      histopathology, including both conventional hematoxylin-eosin staining and immune
      staining with antibodies to the S-100 and HMB-45 antigens. The success rate of
      radioguidance in localizing the sentinel lymph node in melanoma patients is
      approximately 98% in institutions that perform a high number of procedures and
      approaches 99% when combined with the vital blue-dye technique. Growing evidence
      of the high correlation between a sentinel lymph node biopsy negative for cancer
      and a negative status for the lymphatic basin-evidence, therefore, of the high
      prognostic value of sentinel node biopsy-has led to the procedure's being
      included in the most recent version of the TNM staging system and starting to
      become the standard of care for patients with cutaneous melanoma.

PMID- 12050329
TI  - Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial
      cells.
AB  - The existence of thyroid stunning (i.e., inhibited thyroidal iodide uptake after
      administration of diagnostic amounts of (131)I) is controversial and is currently
      a subject of debate. To our knowledge, the stunning phenomenon has not been
      investigated previously in vitro. METHODS: Growth-arrested porcine thyroid cells
      that formed a tight and polarized monolayer in a bicameral chamber were
      irradiated with 3-80 Gy (131)I present in the surrounding culture medium for 48
      h. The iodide transport capacity after irradiation was evaluated 3 d later by
      measuring the transepithelial (basal to apical) flux of trace amounts of (125)I.
      RESULTS: The basal-to-apical (125)I transport decreased with increasing absorbed
      dose acquired from (131)I; a nearly 50% reduction was observed already at 3 Gy.
      Stable iodide at the same molarity as (131)I (10(-8) mol/L) had no effect on the
      (125)I transport. Cell number and epithelial integrity were not affected by
      irradiation. CONCLUSION: Stunning of iodide transport is detected after (131)I
      irradiation of cultured thyroid cells. The degree of inhibition of transport is
      dependent on the absorbed dose.

PMID- 12050330
TI  - Is thyroid stunning a real phenomenon or just fiction?

PMID- 12050331
TI  - The synthesis and radiolabeling of 2-nitroimidazole derivatives of cyclam and
      their preclinical evaluation as positive markers of tumor hypoxia.
AB  - The cyclam ligand (1,4,8,11-tetraazacyclotetradecane) was condensed with various
      azomycin-containing synthons to produce chemical compounds that could chelate
      radioactive metals. It was expected that these radiolabeled markers would become
      bound selectively to hypoxic cells on the bioreduction of their azomycin
      substituent. METHODS: The markers were radiolabeled with (99m)Tc, (67)Cu, or
      (64)Cu. Their uptake and binding to tumor cells in vitro was characterized as a
      function of time and oxygen concentration. These data defined the hypoxia
      specific factor, the ratio of the initial rate of marker binding to severely
      hypoxic relative to aerobic cells. In addition, the concentration of oxygen (in
      the equilibrium gas phase) that inhibited binding to 50% of the maximum rate was
      determined. The in vivo biodistribution and clearance kinetics of the favorable
      markers were investigated with severe combined immune deficiency mice bearing EMT
      6 tumors whose radiobiologic hypoxic fraction (RHF) was approximately 40%. The
      specific activity (percentage injected dose per gram [%ID/g]) in normal and tumor
      tissue and the tumor-to-blood and tumor-to-muscle ratios of the optimal markers
      were also measured for Dunning prostate carcinomas of anaplastic (RHF = 15%-20%)
      and well-differentiated (RHF < 1%) histology growing in Fischer X Copenhagen
      rats. Planar images were acquired with some markers from these tumor-bearing
      rats. RESULTS: The tumor uptake of these cyclam-based markers is approximately 10
      times higher when they are labeled with copper isotopes than when labeled with
      (99m)Tc. FC-327 and FC-334, di-azomycin-substituted cyclams, exhibited hypoxia
      specific factors > or = 7.0. The oxygen concentration that inhibited their
      binding to 50% of the maximal rate was approximately 0.5% O(2), similar to that
      of the radiobiologic oxygen effect. The %ID/g of (64)Cu-FC-334 retained in EMT-6
      tumors in mice and in the anaplastic and well-differentiated prostate tumors in
      rats 6 h after administration was approximately 6.5, 0.4, and 0.1, respectively.
      Marker activity in tumor was always less than that in liver and kidney. The tumor
      to-blood and tumor-to-muscle ratios of (64)Cu-FC-327 and (64)Cu-FC-334 activity
      in R3327-AT tumor-bearing rats are higher than those observed for (64)Cu-di
      acetyl-bis (N(4)-methylthiosemicarbazone) and approach those of beta-D-(125)I
      iodinated azomycin galactopyranoside, the optimal hypoxia marker of the azomycin
      nucleoside class. CONCLUSION: These data suggest that some azomycin-cyclams
      exhibit good hypoxia-marking potential to tumor cells in vitro and to animal
      tumors of known RHF. Both PET and SPECT could be used to image tumor hypoxia with
      markers labeled with (64)Cu and (67)Cu, respectively.

PMID- 12050332
TI  - Influence of renal function on renal output efficiency.
AB  - The purpose of this study was to quantify the influence of renal function on
      output efficiency (OE) and to evaluate factors that may modify this effect.
      METHODS: Renograms were generated in a computer simulation model by convolution
      of plasma disappearance curves with artificially created retention functions. Ten
      plasma curves were derived from a database corresponding to renal clearances
      ranging from 33 to 405 mL/min. The created retention functions had 3
      characteristics: (a) no output until the minimal transit time (MinTT) followed by
      a linear increase in transit time; (b) ratio of MinTT to mean transit time (MTT)
      equal to 0.3 or 0.8; and (c) MTT between 3 and 60 min, increasing with 1-min
      steps. For each of the 1,160 renograms generated, output efficiency at time (t),
      OE(t), was calculated at 20, 40, and 60 min. Mean and SD of OE(t) for all
      clearances were calculated for MTT values between 5 and 60 min, increasing with 5
      min steps. RESULTS: For the same retention function, different clearances
      resulted in different values of OE(t). The degree of variability of OE(t)
      depended on several factors, including the value of t, the value of MTT, and the
      shape of the retention function, expressed as the MinTT-to-MTT ratio. For OE(20),
      OE(40), and OE(60), the respective maximum SDs were 5.4%, 6.6%, and 7.1% for
      retention functions with a MinTT-to-MTT ratio equal to 0.3, and 6.2%, 8.4%, and
      9.4% for retention functions with a MinTT-to-MTT ratio equal to 0.8. CONCLUSION:
      OE is influenced by renal function. Care should be taken in establishing the
      cutoff values for obstruction, non-obstruction, and the nondiagnostic zone, since
      a change in overall clearance can cause as much as a 20% variation in OE.

PMID- 12050333
TI  - Procedure guideline for therapy of thyroid disease with (131)iodine.

PMID- 12050334
TI  - Images in clinical medicine. Retinal hemorrhages in acute leukemia.

PMID- 12050335
TI  - Sirolimus-eluting coronary stents.

PMID- 12050336
TI  - A randomized comparison of a sirolimus-eluting stent with a standard stent for
      coronary revascularization.
AB  - BACKGROUND: The need for repeated treatment of restenosis of a treated vessel
      remains the main limitation of percutaneous coronary revascularization. Because
      sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle
      cells, we compared a sirolimus-eluting stent with a standard uncoated stent in
      patients with angina pectoris. METHODS: We performed a randomized, double-blind
      trial to compare the two types of stents for revascularization of single, primary
      lesions in native coronary arteries. The trial included 238 patients at 19
      medical centers. The primary end point was in-stent late luminal loss (the
      difference between the minimal luminal diameter immediately after the procedure
      and the diameter at six months). Secondary end points included the percentage of
      in-stent stenosis of the luminal diameter and the rate of restenosis (luminal
      narrowing of 50 percent or more). We also analyzed a composite clinical end point
      consisting of death, myocardial infarction, and percutaneous or surgical
      revascularization at 1, 6, and 12 months. RESULTS: At six months, the degree of
      neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was
      significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the
      standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the
      sirolimus-stent group, as compared with 26.6 percent of those in the standard
      stent group, had restenosis of 50 percent or more of the luminal diameter
      (P<0.001). There were no episodes of stent thrombosis. During a follow-up period
      of up to one year, the overall rate of major cardiac events was 5.8 percent in
      the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001).
      The difference was due entirely to a higher rate of revascularization of the
      target vessel in the standard-stent group. CONCLUSIONS: As compared with a
      standard coronary stent, a sirolimus-eluting stent shows considerable promise for
      the prevention of neointimal proliferation, restenosis, and associated clinical
      events.

PMID- 12050337
TI  - Results of screening colonoscopy among persons 40 to 49 years of age.
AB  - BACKGROUND: The prevalence of colorectal lesions in persons 40 to 49 years of
      age, as identified on colonoscopy, has not been determined. METHODS: We reviewed
      the procedure and pathology reports for 906 consecutive persons 40 to 49 years of
      age who voluntarily participated in an employer-based screening-colonoscopy
      program. The histologic features of lesions that were identified and removed on
      endoscopy were categorized according to those of the most advanced lesion removed
      proximally (up to the junction of the splenic flexure and the descending colon)
      and the most advanced lesion removed distally. An advanced lesion was defined as
      an adenoma at least 1 cm in diameter, a polyp with villous histologic features or
      severe dysplasia, or a cancer. RESULTS: Among those who underwent colonoscopic
      screening, 78.9 percent had no detected lesions, 10.0 percent had hyperplastic
      polyps, 8.7 percent had tubular adenomas, and 3.5 percent had advanced neoplasms,
      none of which were cancerous (95 percent confidence interval for cancer, 0 to 0.4
      percent). Eighteen of 33 advanced neoplasms (55 percent) were located distally
      and were potentially within reach of a sigmoidoscope. If these results are
      applicable to the general population, at least 250 persons, and perhaps 1000 or
      more, would need to be screened to detect one cancer in this age group.
      CONCLUSIONS: Colonoscopic detection of colorectal cancer is uncommon in
      asymptomatic persons 40 to 49 years of age. The noncancerous lesions are equally
      distributed proximally and distally. The low yield of screening colonoscopy in
      this age group is consistent with current recommendations about the age at which
      to begin screening in persons at average risk.

PMID- 12050338
TI  - Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis.
AB  - BACKGROUND: Hereditary, autosomal dominant amyloidosis, caused by mutations in
      the genes encoding transthyretin, fibrinogen A alpha-chain, lysozyme, or
      apolipoprotein A-I, is thought to be extremely rare and is not routinely included
      in the differential diagnosis of systemic amyloidosis unless there is a family
      history. METHODS: We studied 350 patients with systemic amyloidosis, in whom a
      diagnosis of the light-chain (AL) type of the disorder had been suggested by
      clinical and laboratory findings and by the absence of a family history, to
      assess whether they had amyloidogenic mutations. RESULTS: Amyloidogenic mutations
      were present in 34 of the 350 patients (9.7 percent), most often in the genes
      encoding fibrinogen A alpha-chain (18 patients) and transthyretin (13 patients).
      In all 34 of these patients, the diagnosis of hereditary amyloidosis was
      confirmed by additional investigations. A low-grade monoclonal gammopathy was
      detected in 8 of the 34 patients (24 percent). CONCLUSIONS: A genetic cause
      should be sought in all patients with amyloidosis that is not the reactive
      systemic amyloid A type and in whom confirmation of the AL type cannot be
      obtained.

PMID- 12050339
TI  - Central nervous system infection in congenital syphilis.
AB  - BACKGROUND: Identification of infants with Treponema pallidum infection of the
      central nervous system remains challenging. METHODS: We used rabbit-infectivity
      testing of the cerebrospinal fluid to detect T. pallidum infection of the central
      nervous system in infants born to mothers with syphilis. The results were
      compared with those of clinical, radiographic, and conventional laboratory
      evaluations; IgM immunoblotting of serum and cerebrospinal fluid; polymerase
      chain-reaction (PCR) assay testing of serum or blood and cerebrospinal fluid; and
      rabbit-infectivity testing of serum or blood. RESULTS: Spirochetes were detected
      in the cerebrospinal fluid of 19 of 148 infants by rabbit-infectivity testing.
      Exposure of the infant to antibiotics before cerebrospinal fluid was obtained for
      rabbit-infectivity testing was associated with a negative test result (P=0.001).
      Spirochetes were detected in the cerebrospinal fluid in 17 of 76 infants (22
      percent) who had no prior antibiotic exposure. These 17 infants included 41
      percent (16 of 39) of those with some abnormality on clinical, laboratory, or
      radiographic evaluation; 60 percent (15 of 25) of those with abnormal findings on
      physical examination that were consistent with congenital syphilis; and 41
      percent (17 of 41) of those with a positive result on IgM immunoblotting or PCR
      testing of serum, blood, or cerebrospinal fluid, or a positive result on rabbit
      infectivity testing of serum or blood. Only one infant who had normal findings on
      clinical evaluation had a positive cerebrospinal fluid rabbit-infectivity test.
      Overall, central nervous system infection was best predicted by IgM
      immunoblotting of serum or PCR assay of serum or blood. CONCLUSIONS: Most infants
      with T. pallidum infection of the central nervous system can be identified by
      physical examination, conventional laboratory tests, and radiographic studies.
      However, the identification of all such infants requires the use of additional
      tests, including IgM immunoblotting and PCR assay.

PMID- 12050340
TI  - Images in clinical medicine. Interstitial keratitis as the initial expression of
      syphilitic reactivation.

PMID- 12050341
TI  - Cost effectiveness of aspirin, clopidogrel, or both for secondary prevention of
      coronary heart disease.
AB  - BACKGROUND: Both aspirin and clopidogrel reduce the rate of cardiovascular events
      in patients with coronary heart disease. We estimated the cost effectiveness of
      the increased use of aspirin, clopidogrel, or both for secondary prevention in
      patients with coronary heart disease. METHODS: We used the Coronary Heart Disease
      Policy Model, a computer simulation of the U.S. population, to estimate the
      incremental cost effectiveness (in dollars per quality-adjusted years of life
      gained) of four strategies in patients over 35 years of age with coronary disease
      from 2003 to 2027: aspirin for all eligible patients (i.e., those who were not
      allergic to or intolerant of aspirin), aspirin for all eligible patients plus
      clopidogrel for patients who were ineligible for aspirin, clopidogrel for all
      patients, and the combination of aspirin for all eligible patients plus
      clopidogrel for all patients. RESULTS: The extension of aspirin therapy from the
      current levels of use to all eligible patients for 25 years would have an
      estimated cost-effectiveness ratio of about $11,000 per quality-adjusted year of
      life gained. The addition of clopidogrel for the 5 percent of patients who are
      ineligible for aspirin would cost about $31,000 per quality-adjusted year of life
      gained. Clopidogrel alone in all patients or in routine combination with aspirin
      had an incremental cost of more than $130,000 per quality-adjusted year of life
      gained and remained financially unattractive across a wide range of assumptions.
      However, clopidogrel alone or in combination with aspirin would cost less than
      $50,000 per quality-adjusted year of life gained if its price were reduced by 70
      to 82 percent, to $1.00 and $0.60 per day, respectively. CONCLUSIONS: Increased
      prescription of aspirin for secondary prevention of coronary heart disease is
      attractive from a cost-effectiveness perspective. Because clopidogrel is more
      costly, its incremental cost effectiveness is currently unattractive, unless its
      use is restricted to patients who are ineligible for aspirin.

PMID- 12050342
TI  - Clinical practice. Carpal tunnel syndrome.

PMID- 12050343
TI  - Clinical problem-solving. Diagnosis still in question.

PMID- 12050344
TI  - Sporadic cases of hereditary systemic amyloidosis.

PMID- 12050345
TI  - When increased therapeutic benefit comes at increased cost.

PMID- 12050346
TI  - What's ahead for health insurance in the United States?

PMID- 12050347
TI  - Oral contraceptives and the risk of myocardial infarction.

PMID- 12050348
TI  - Diabetes prevention.

PMID- 12050349
TI  - Rituximab plus CHOP for diffuse large-B-cell lymphoma.

PMID- 12050350
TI  - The interval between pregnancies and preeclampsia.

PMID- 12050351
TI  - Uterine sarcoma associated with tamoxifen use.

PMID- 12050352
TI  - Food allergies and kissing.

PMID- 12050353
TI  - Interferons mediate terminal differentiation of human cortical thymic epithelial
      cells.
AB  - In the thymus, epithelial cells comprise a heterogeneous population required for
      the generation of functional T lymphocytes, suggesting that thymic epithelium
      disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a
      previous report, we demonstrated that in vitro, measles virus induced
      differentiation of cortical thymic epithelial cells as characterized by (i) cell
      growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as
      a final step of this process. In the present report, we have analyzed the
      mechanisms involved. First, measles virus-induced differentiation of thymic
      epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta)
      secretion. In addition, transfection with double-stranded RNA, a common
      intermediate of replication for a broad spectrum of viruses, is reported to
      similarly mediate thymic epithelial cell differentiation through IFN-beta
      induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN
      gamma was sufficient to induce differentiation and apoptosis of uninfected thymic
      epithelial cells. These observations suggested that interferon secretion by
      either infected cells or activated leukocytes, such as plasmacytoid dendritic
      cells or lymphocytes, may induce thymic epithelium disruption in a pathological
      context. Thus, we have identified a new mechanism that may contribute to thymic
      atrophy and altered T-cell lymphopoiesis associated with many infections.

PMID- 12050355
TI  - STAT2 acts as a host range determinant for species-specific paramyxovirus
      interferon antagonism and simian virus 5 replication.
AB  - The antiviral state induced by alpha/beta interferon (IFN-alpha/beta) is a
      powerful selective pressure for virus evolution of evasive strategies. The
      paramyxoviruses simian virus 5 (SV5) and human parainfluenza virus 2 (HPIV2)
      overcome IFN-alpha/beta responses through the actions of their V proteins, which
      induce proteasomal degradation of cellular IFN-alpha/beta-activated signal
      transducers and activators of transcription STAT1 and STAT2. SV5 infection
      induces STAT1 degradation and IFN-alpha/beta inhibition efficiently in human
      cells but not in mouse cells, effectively restricting SV5 host range. Here, the
      cellular basis for this species specificity is demonstrated to result from
      differences between human and murine STAT2. Expression in mouse cells of full
      length or truncated human STAT2 cDNA is sufficient to permit antagonism of
      endogenous murine IFN-alpha/beta signaling by SV5 and HPIV2 V proteins.
      Furthermore, virus-induced STAT protein degradation is observed in mouse cells
      only in the presence of ectopically expressed human STAT2. The results indicate
      that STAT2 acts as an intracellular determinant of paramyxovirus host range
      restriction, which contributes to the species specificity of virus replication,
      and that human STAT2 can confer a growth advantage for SV5 in the murine host.

PMID- 12050354
TI  - Highly pathogenic simian immunodeficiency virus mne variants that emerge during
      the course of infection evolve enhanced infectivity and the ability to
      downregulate CD4 but not class I major histocompatibility complex antigens.
AB  - The replicative, cytopathic, and antigenic properties of simian immunodeficiency
      virus (SIV) variants influence its replication efficiency in vivo. To further
      define the viral properties and determinants that may be important for high-level
      replication in vivo and progression to AIDS, we compared a minimally pathogenic
      SIVmne molecular clone with two highly pathogenic variants cloned from late
      stages of infection. Both variants had evolved greater infectivity than the
      parental clone due to mutations in nef. Interestingly, a pol determinant in one
      of the highly pathogenic variants also contributed to its increased infectivity.
      Furthermore, because replication in vivo may also be influenced by the ability of
      a virus to evade the cellular immune response of the host, we examined whether
      the variants were more capable of downregulating surface expression of class I
      major histocompatibility complex (MHC). Decreased MHC class I expression was not
      observed in cells infected with any of the viruses. Furthermore, the Nef proteins
      of the highly pathogenic variants only slightly reduced surface MHC class I
      expression in transfected cells, although they efficiently downregulated CD4.
      Together, these data demonstrate that mutations which can enhance viral
      infectivity, as well as CD4 downregulation, may be important for efficient
      replication of SIV in the host. However, Nef-mediated reduction of MHC class I
      expression does not appear to be critical for the increased in vivo replicative
      ability of highly pathogenic late variants.

PMID- 12050356
TI  - The envelope glycoprotein of human endogenous retrovirus type W uses a divergent
      family of amino acid transporters/cell surface receptors.
AB  - The human endogenous retrovirus type W (HERV-W) family includes proviruses with
      intact protein-coding regions that appear to be under selection pressure,
      suggesting that some HERV-W proviruses may remain active in higher primates. The
      envelope glycoprotein (Env) encoded by HERV-W is highly fusogenic, is naturally
      expressed in human placental syncytiatrophoblasts, and has been reported to
      function as a superantigen in lymphocyte cultures. Recent evidence suggested that
      HERV-W Env can mediate syncytium formation by interacting with the human sodium
      dependent neutral amino acid transporter type 2 (hASCT2; gene name, SLC1A5) (J.
      L. Blond, D. Lavillette, V. Cheynet, O. Bouton, G. Oriol, S. Chapel-Fernandez, B.
      Mandrand, F. Mallet, and F.-L. Cosset, J. Virol. 74:3321-3329, 2000) and that it
      can pseudotype human immunodeficiency virus cores (D. S. An, Y. Xie, and I. S. Y.
      Chen, J. Virol. 75:3488-3489, 2001). By using cell-cell fusion and pseudotype
      virion infection assays, we found that HERV-W Env efficiently uses both hASCT2
      and the related transporter hASCT1 (gene name, SLC1A4) as receptors. In addition,
      although HERV-W Env mediates only slight syncytium formation or infection of
      mouse cells, it utilizes the mouse transporters mASCT1 and mASCT2 when their
      sites for N-linked glycosylation are eliminated by mutagenesis. Consistent with
      their role as a battlefield in host-virus coevolution, the viral recognition
      regions in ASCT1 and ASCT2 of humans and mice are highly divergent compared with
      other regions of these proteins, and their ratios of nonsynonymous to synonymous
      nucleotide sequence changes are extremely large. The recognition of ASCT1 and
      ASCT2 despite this divergence of their sequences strongly suggests that the use
      of both receptors has been highly advantageous for survival and evolution of the
      HERV-W family of retroviruses.

PMID- 12050357
TI  - Intracutaneous DNA vaccination with the E8 gene of cottontail rabbit
      papillomavirus induces protective immunity against virus challenge in rabbits.
AB  - The cottontail rabbit papillomavirus (CRPV)-rabbit model has been used in several
      studies for testing prophylactic and therapeutic papillomavirus vaccines. Earlier
      observations had shown that the CRPV nonstructural genes E1, E2, and E6 induced
      strong to partial protective immunity against CRPV infection. In this study, we
      found that CRPV E8 immunization eliminated virus-induced papillomas in EIII/JC
      inbred rabbits (100%) and provided partial protection (55%) against virus
      challenge in outbred New Zealand White rabbits. CRPV-E8 is a small open reading
      frame, coding for a 50-amino-acid protein, that is colinear with the CRPV E6 gene
      and has features similar to those of the bovine papillomavirus and human
      papillomavirus E5 genes. Papillomas that grew on E8-vaccinated outbred rabbits
      were significantly smaller than those on vector-vaccinated rabbits (P < 0.01; t
      test). Delayed-type hypersensitivity skin tests showed that some of the E8
      vaccinated rabbits had positive responses to E8-specific peptides.

PMID- 12050358
TI  - Human monocytic cell lines transformed in vitro by Epstein-Barr virus display a
      type II latency and LMP-1-dependent proliferation.
AB  - Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in
      vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other
      herpesviruses, EBV is not described as an infectious agent for monocytes.
      However, recent papers described in vitro infection of monocytes leading to
      abortive or transient viral expression. In the present study, we report the
      characterization of E1, a monocytic cell line infected and transformed by EBV.
      This cell line was derived from an LCL by a drastic electroporation and selection
      of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed
      surface molecules of monocytic lineage (CD14, major histocompatibility complex
      class II, and CD80) and the c-fms gene, a highly specific marker for the
      monocytic lineage. This cell line is able to phagocytose and secrete
      proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and
      IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell
      line obtained from one of these tumors (TE1) displayed immunophenotype and
      functional properties similar to those of E1. We detected the presence of the EBV
      genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not
      EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the
      phenotype of these monocytic cell lines, as demonstrated by down-regulation of
      cell proliferation and membrane intercellular adhesion molecule 1 expression due
      to an LMP-1 antisense strategy. This is the first description of a latently
      infected human monocytic cell line and the first direct demonstration of an
      instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines
      expressing a type II latency.

PMID- 12050359
TI  - Phosphorylation of transcription factor Sp1 during herpes simplex virus type 1
      infection.
AB  - The expression of most herpes simplex virus type 1 (HSV-1) immediate-early (IE)
      and early (E) genes decreases late in productive infection. IE and E promoters
      contain various binding sites for cellular activators, including sites for Sp1,
      upstream of the TATA box, while late gene promoters generally lack such sites. To
      address the possibility that Sp1 function may be altered during the course of
      infection, the modification state and activity of Sp1 were investigated as a
      function of infection. Sp1 was quantitatively phosphorylated in HSV-1-infected
      cells without a significant change in abundance. The kinetics of accumulation of
      phosphorylated Sp1 immediately preceded the decline in E gene (thymidine kinase
      gene [tk]) mRNA abundance. Phosphorylation of Sp1 required ICP4; however, the
      proportion of phosphorylated Sp1 was reduced during infection in the presence of
      phosphonoacetic acid or in the absence of ICP27. While the DNA binding activity
      of Sp1 was not greatly affected by phosphorylation, the ability of phosphorylated
      Sp1 isolated from HSV-infected cells to activate transcription in vitro was
      decreased. These studies suggest that modification of Sp1 may contribute to the
      decrease of IE and E gene expression late in infection.

PMID- 12050360
TI  - Identification of two cross-neutralizing linear epitopes within the L1 major
      capsid protein of human papillomaviruses.
AB  - The neutralizing activities of polyclonal antibodies and monoclonal antibodies
      (MAbs) obtained by immunization of mice with L1 virus-like particles (VLPs) were
      investigated by using pseudovirion infectivity assays for human papillomavirus
      type 16 (HPV-16), HPV-31, HPV-33, HPV-45, HPV-58, and HPV-59 to obtain a better
      definition of cross-neutralization between high-risk HPVs. In this study, we
      confirmed and extended previous studies indicating that most genital HPV
      genotypes represent separate serotypes, and the results suggest that the
      classification of serotypes is similar to that of genotypes. In addition, three
      cross-neutralizing MAbs were identified (HPV-16.J4, HPV-16.I23, and HPV-33.E12).
      MAb HPV-16.J4 recognized a conserved linear epitope located within the FG loop of
      the L1 protein, and HPV-16.I23 recognized another located within the DE loop. The
      results suggested that reactivity of MAb HPV-16.I23 to L1 protein is lost when
      leucine 152 of the HPV-16 L1 protein is replaced by phenylalanine. This confirmed
      the existence of linear epitopes within the L1 protein that induce neutralizing
      antibodies, and this is the first evidence that such linear epitopes induce cross
      neutralization. However, the cross-neutralization induced by L1 VLPs represents
      less than 1% of the neutralizing activity induced by the dominant conformational
      epitopes, and it is questionable whether this is sufficient to offer cross
      protection in vivo.

PMID- 12050361
TI  - Gammadelta T cells promote a Th1 response during coxsackievirus B3 infection in
      vivo: role of Fas and Fas ligand.
AB  - Fas/Fas ligand (FasL) interactions regulate disease outcome in coxsackievirus B3
      (CVB3)-induced myocarditis. MRL(+/+) mice infected with CVB3 develop severe
      myocarditis, a dominant CD4(+) Th1 (gamma interferon [IFN-gamma(+)]) response to
      the virus, and a predominance of gammadelta T cells in the myocardial
      infiltrates. MRL lpr/lpr and MRL gld/gld mice, which lack normal expression of
      Fas and express a mutated FasL, respectively, have minimal myocarditis and show a
      dominant CD4(+) Th2 (interleukin-4 [IL-4(+)]) phenotype to CVB3. Spleen cells
      from virus-infected wild-type, lpr, and gld animals proliferate equally to virus
      in vitro. Adoptive transfer of gammadelta T cells from hearts of CVB3-infected
      MRL(+/+) mice (FasL(+)) into infected MRL gld/gld recipients (FasL(-)/Fas(+))
      restores both disease susceptibility and Th1 cell phenotype. However, transfer of
      these cells into MRL lpr/lpr recipients (FasL(+)/Fas(-)) did not promote
      myocarditis and the viral response remained Th2 biased. This paralleled the
      expression of very high surface levels of FasL by myocardial gammadelta T cells,
      as well as their propensity to selectively lyse Th2 virus-specific CD4(+) T
      cells. These results demonstrate that Fas/FasL interactions conferred by
      gammadelta T cells on lymphocyte subpopulations may regulate the cytokine
      response to CVB3 infection and pathogenicity.

PMID- 12050362
TI  - Turnover of hepatitis B virus X protein is regulated by damaged DNA-binding
      complex.
AB  - Mammalian hepatitis B viruses encode an essential regulatory protein, termed X,
      which may also be implicated in liver cancer development associated with chronic
      infection. X protein, also referred to as HBx in human virus and WHx in woodchuck
      virus, has been reported to bind to a number of cellular proteins, including the
      DDB1 subunit of the damaged DNA-binding (DDB) complex. Our previous work provided
      genetic evidence for the importance of WHx-DDB1 interaction in both the activity
      of the X protein and establishment of viral infection in woodchucks. In the
      present study, a direct action of DDB1 on the X protein is documented. Physical
      interaction between the two proteins leads to an increase in X protein stability.
      This effect results from protection of the viral protein from proteasome-mediated
      degradation. Protection of WHx is overcome in the presence DDB2, the second
      subunit of the DDB heterodimer. In keeping with observations reported for HBx,
      DDB2 was found to directly bind to WHx. Nonetheless, the counteracting effect of
      DDB2 on X stabilization requires DDB2-DDB1 interaction. Taken together, these
      findings substantiate the physical and functional connection between the X
      protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of
      the viral protein.

PMID- 12050363
TI  - Rotavirus genome segment 7 (NSP3) is a determinant of extraintestinal spread in
      the neonatal mouse.
AB  - We used the neonatal mouse model of rotavirus infection to study extraintestinal
      spread following oral inoculation. Five-day-old pups were inoculated with either
      SA11-Cl3, SA11-Cl4, SA11-4F, RRV, or B223. By using virus detection in the liver
      as a proxy determination for extraintestinal spread, rotavirus strains capable of
      extraintestinal spread at high frequency (rhesus rotavirus [RRV]) and very low
      frequency (SA11-Cl4) were identified. Both strains productively infected the
      gastrointestinal tract. Oral inoculation of mice with RRV/ SA11-Cl4 reassortants
      and determination of virus titers in the gut and liver revealed that the
      extraintestinal spread phenotype segregated with RRV genome segment 7 to a high
      level of significance (P = 10(-3)). RRV segment 7 also segregated with the growth
      of virus in the gut (P = 10(-5)). Although infection of the gut was clearly
      required for tropism to the liver, there was no correlation between virus titers
      in the gut and detection of virus in the liver. Five days after intraperitoneal
      administration to bypass the gut barrier to virus spread, RRV and SA11-Cl4 both
      were recovered in the liver. However, only RRV was found in the liver following
      subcutaneous inoculation, suggesting that this peripheral site presented a
      similar barrier to virus spread as the gut. Sequence analysis of segment 7 from
      parental RRV and SA11-Cl4 and selected reassortants showed that (i) amino acid
      differences were distributed throughout the coding sequences and not concentrated
      in any particular functional motif and (ii) parental sequence was preserved in
      reassortants. These data support the hypothesis that NSP3, coded for by genome
      segment 7, plays a significant role in viral growth in the gut and spread to
      peripheral sites. The mechanism of NSP3-mediated tropism is under investigation.

PMID- 12050364
TI  - Influence of a putative intermolecular interaction between core and the pre-S1
      domain of the large envelope protein on hepatitis B virus secretion.
AB  - Virion release of hepatitis B virus (HBV) from hepatocytes is a tightly regulated
      event. It is a dogma that only the mature HBV genome is preferentially allowed to
      export from the intracellular compartment (J. Summers and W. S. Mason, Cell
      29:403-415, 1982). Recently, an "immature secretion" phenotype of a highly
      frequent naturally occurring HBV variant containing a leucine residue at amino
      acid 97 of the core protein was identified. Unlike wild-type HBV, this variant
      secretes almost equal amounts of mature and immature genomes. This phenomenon is
      not caused by any instability of core particles or by any deficiency in viral
      reverse transcription (T. T. Yuan, P. C. Tai, and C. Shih, J. Virol. 73:10122
      10128, 1999). In this study, our kinetic analysis of virion secretion of the
      mutant F97L (phenylalanine to leucine) indicates that the secretion of its
      immature genome does not occur earlier than that of its mature genome. In
      addition, the secretion kinetics of the mature genomes are comparable between the
      wild-type HBV and the mutant F97L. Therefore, the immature secretion phenomenon
      of mutant F97L is not caused by premature secretion or more efficient secretion.
      Previously, we hypothesized that the immature secretion phenotype is probably
      caused by the aberrant interaction between its mutant core and wild-type envelope
      proteins. Here, we further demonstrated that a pre-S1 envelope mutation at
      position 119, changing an alanine (A) to a phenylalanine (F), can offset the
      immature secretion phenotype of the mutant I97L (isoleucine to leucine) and
      successfully restore the wild-type-like selective export of the mature genome of
      the double mutant pre-S1-A119F/core-I97L.

PMID- 12050365
TI  - Parvovirus initiator protein NS1 and RPA coordinate replication fork progression
      in a reconstituted DNA replication system.
AB  - We show here that the DNA helicase activity of the parvoviral initiator protein
      NS1 is highly directional, binding to the single strand at a recessed 5' end and
      displacing the other strand while progressing in a 3'-to-5' direction on the
      bound strand. NS1 and a cellular site-specific DNA binding factor, PIF, also
      known as glucocorticoid modulating element binding protein, bind to the left-end
      minimal replication origin of minute virus of mice, forming a ternary complex. In
      this complex, NS1 is activated to nick one DNA strand, becoming covalently
      attached to the 5' end of the nick in the process and providing a 3' OH for
      priming DNA synthesis. In this situation, the helicase activity of NS1 did not
      displace the nicked strand, but the origin duplex was distorted by the NS1-PIF
      complex, as assayed by its sensitivity to KMnO(4) oxidation, and a stretch of
      about 14 nucleotides on both strands of the nicked origin underwent limited
      unwinding. Addition of Escherichia coli single-stranded DNA binding protein (SSB)
      did not lead to further unwinding. However, addition of recombinant human single
      stranded DNA binding protein (RPA) to the initiation reaction catalyzed extensive
      unwinding of the nicked origin, suggesting that RPA may be required to form a
      functional replication fork. Accordingly, the unwinding mediated by NS1 and RPA
      promoted processive leading-strand synthesis catalyzed by recombinant human DNA
      polymerase delta, PCNA, and RFC, using the minimal left-end origin cloned in a
      plasmid as a template. The requirement for RPA, rather than SSB, in the unwinding
      reaction indicated that specific NS1-RPA protein interactions were formed. NS1
      was tested by enzyme-linked immunosorbent assay for binding to two- or three
      subunit RPA complexes expressed from recombinant baculoviruses. NS1 efficiently
      bound each of the baculovirus-expressed complexes, indicating that the small
      subunit of RPA is not involved in specific NS1 binding. No NS1 interactions were
      observed with E. coli SSB or other proteins included as controls.

PMID- 12050367
TI  - Potent inhibition of human immunodeficiency virus type 1 replication by template
      analog reverse transcriptase inhibitors derived by SELEX (systematic evolution of
      ligands by exponential enrichment).
AB  - RNA aptamers derived by SELEX (systematic evolution of ligands by exponential
      enrichment) and specific for human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) bind at the template-primer cleft with high affinity and
      inhibit its activity. In order to determine the potential of such template analog
      RT inhibitors (TRTIs) to inhibit HIV-1 replication, 10 aptamers were expressed
      with flanking, self-cleaving ribozymes to generate aptamer RNA transcripts with
      minimal flanking sequences. From these, six aptamers (70.8,13, 70.15, 80.55,65,
      70.28, 70.28t34, and 1.1) were selected based on binding constants (K(d)) and the
      degree of inhibition of RT in vitro (50% inhibitory concentration [IC(50)]).
      These six aptamers were each stably expressed in 293T cells followed by
      transfection of a molecular clone of HIV(R3B). Analysis of the virion particles
      revealed that the aptamers were encapsidated into the virions released and that
      the packaging of the viral genomic RNA or the cognate primer, tRNA(Lys)(3), was
      apparently unaffected. Infectivity of virions produced from 293T cell lines
      expressing the aptamers, as measured by infecting LuSIV reporter cells, was
      reduced by 90 to 99.5% compared to virions released from cells not expressing any
      aptamers. PCR analysis of newly made viral DNA upon infection with virions
      containing any of the three aptamers with the strongest binding affinities
      (70.8,13, 70.15, and 80.55,65) showed that all three were able to form the minus
      strand strong-stop DNA. However, virions with the aptamers 70.8 and 70.15 were
      defective for first-strand transfer, suggesting an early block in viral reverse
      transcription. Jurkat T cells expressing each of the three aptamers, when
      infected with HIV(R3B), completely blocked the spread of HIV in culture. We found
      that the replication of nucleoside analog RT inhibitor-, nonnucleoside analog RT
      inhibitor-, and protease inhibitor-resistant viruses was strongly suppressed by
      the three aptamers. In addition, some of the HIV subtypes were severely inhibited
      (subtypes A, B, D, E, and F), while others were either moderately inhibited
      (subtypes C and O) or were naturally resistant to inhibition (chimeric A/D
      subtype). As virion-encapsidated TRTIs can predispose virions for inhibition
      immediately upon entry, they should prove to be efficacious agents in gene
      therapy approaches for AIDS.

PMID- 12050366
TI  - Characterization of a spontaneous 9.5-kilobase-deletion mutant of murine
      gammaherpesvirus 68 reveals tissue-specific genetic requirements for latency.
AB  - Murine gammaherpesvirus 68 (gammaHV68 [also known as MHV-68]) establishes a
      latent infection in mice, providing a small-animal model with which to identify
      host and viral factors that regulate gammaherpesvirus latency. While gammaHV68
      establishes a latent infection in multiple tissues, including splenocytes and
      peritoneal cells, the requirements for latent infection within these tissues are
      poorly defined. Here we report the characterization of a spontaneous 9.5-kb
      deletion mutant of gammaHV68 that lacks the M1, M2, M3, and M4 genes and eight
      viral tRNA-like genes. Previously, this locus has been shown to contain the
      latency-associated M2, M3, and viral tRNA-like genes. Through characterization of
      this mutant, we found that the M1, M2, M3, M4 genes and the viral tRNA-like genes
      are dispensable for (i) in vitro replication and (ii) the establishment and
      maintenance of latency in vivo and reactivation from latency following
      intraperitoneal infection. In contrast, following intranasal infection with this
      mutant, there was a defect in splenic latency at both early and late times, a
      phenotype not observed in peritoneal cells. These results indicate (i) that there
      are different genetic requirements for the establishment of latency in different
      latent reservoirs and (ii) that the genetic requirements for latency depend on
      the route of infection. While some of these phenotypes have been observed with
      specific mutations in the M1 and M2 genes, other phenotypes have never been
      observed with the available gammaHV68 mutants. These studies highlight the
      importance of loss-of-function mutations in defining the genetic requirements for
      the establishment and maintenance of herpesvirus latency.

PMID- 12050368
TI  - Differential effect of murine alpha/beta interferon transgenes on antagonization
      of herpes simplex virus type 1 replication.
AB  - Alpha/beta interferons (IFN-alpha/beta) are potent, endogenous antiviral
      cytokines that suppress the replication of RNA and DNA viruses, including herpes
      simplex virus type 1 (HSV-1). The present study compared the efficacies of IFN
      alpha/beta transgenes, including IFN-alpha1, -alpha4, -alpha5, -alpha6, -alpha9,
      and -beta, against HSV-1 infection. L929 cells transfected with the IFN
      alpha/beta transgenes produced similar levels of IFN, as measured by bioassay and
      enzyme-linked immunosorbent assay. In addition, transfected cells were less
      susceptible to HSV-1 infection than were cells transfected with a plasmid vector
      control. The murine IFN-beta plasmid construct exhibited the greatest reduction,
      while the murine IFN-alpha5 transgene showed a modest inhibitory effect in viral
      titers recovered from the supernatants of transfected, infected L929 cultures.
      Consistent with this observation, the IFN-beta transgene antagonized viral
      transcript levels, including infected cell protein 27, thymidine kinase, and
      glycoprotein B, to a greater extent than did the IFN-alpha transgenes at 6 to 10
      h postinfection as determined by real-time PCR. Cells transfected with the IFN
      alpha4, IFN-alpha9, or IFN-beta transgenes showed the greatest reduction in viral
      protein expression relative to the other transfected cells, which was associated
      with increased STAT1 expression. The absence of the IFN-responsive protein kinase
      R (PKR) gene completely abrogated the antiviral induction by all IFN-alpha/beta
      against HSV-1. In the absence of RNase L, viral yields were increased 10-fold,
      but the antiviral effect of IFN was either unaffected or enhanced. These results
      suggest that the predominant IFN-mediated, antiviral pathway during HSV-1
      infection taken by IFN-alpha/beta in L929 cells utilizes PKR.

PMID- 12050369
TI  - Induction of CD8 T-cell-specific systemic and mucosal immunity against herpes
      simplex virus with CpG-peptide complexes.
AB  - Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful
      adjuvant activity in vivo and in vitro. Administered with antigen they induce a
      population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6
      mice with bioactive CpG ODN combined with an immunodominant epitope derived from
      herpes simplex virus (HSV) glycoprotein B (amino acids 498 to 505; SSIEFARL) and
      analyzed the magnitude and durability of the peptide-specific response. The
      effectiveness of the CD8+ T-cell response as measured by peptide-specific
      tetramers, peptide-induced intracellular gamma interferon expression, and
      resistance to systemic and mucosal challenge during the acute and memory phases
      was compared with the response induced by immunization with recombinant vaccinia
      virus encoding SSIEFARL as a minigene (VvgB(498-505)). Confirming the reports of
      others, our results demonstrate that the CpG ODN-peptide approach generates an
      antigen-specific CD8+ T-cell population, but the frequency of CD8+ T cells is
      lower than that induced by VvgB(498-505). Nevertheless, the protection level was
      comparable when mice were systemically and mucosally challenged during the acute
      phase. However, such responses by both groups waned with time and were
      functionally less effective. Still, our results indicate that the CpG ODN-peptide
      immunization system holds promise as a means of selectively inducing a CD8+ T
      cell response against HSV.

PMID- 12050370
TI  - The majority of infiltrating CD8+ T cells in the central nervous system of
      susceptible SJL/J mice infected with Theiler's virus are virus specific and fully
      functional.
AB  - Theiler's virus infection of the central nervous system (CNS) induces an immune
      mediated demyelinating disease in susceptible mouse strains, such as SJL/J, and
      serves as a relevant infectious model for human multiple sclerosis. It has been
      previously suggested that susceptible SJL/J mice do not mount an efficient
      cytotoxic T-lymphocyte (CTL) response to the virus. In addition, genetic studies
      have shown that resistance to Theiler's virus-induced demyelinating disease is
      linked to the H-2D major histocompatibility complex class I locus, suggesting
      that a compromised CTL response may contribute to the susceptibility of SJL/J
      mice. Here we show that SJL/J mice do, in fact, generate a CD8(+) T-cell response
      in the CNS that is directed against one dominant (VP3(159-166)) and two
      subdominant (VP1(11-20) and VP3(173-181)) capsid protein epitopes. These virus
      specific CD8(+) T cells produce gamma interferon (IFN-gamma) and lyse target
      cells in the presence of the epitope peptides, indicating that these CNS
      infiltrating CD8(+) T cells are fully functional effector cells. Intracellular
      IFN-gamma staining analysis indicates that greater than 50% of CNS-infiltrating
      CD8(+) T cells are specific for these viral epitopes at 7 days postinfection.
      Therefore, the susceptibility of SJL/J mice is not due to the lack of an early
      functional Theiler's murine encephalomyelitis virus-specific CTL response.
      Interestingly, T-cell responses to all three epitopes are restricted by the H
      2K(s) molecule, and this skewed class I restriction may be associated with
      susceptibility to demyelinating disease.

PMID- 12050371
TI  - Previously infected and recovered chimpanzees exhibit rapid responses that
      control hepatitis C virus replication upon rechallenge.
AB  - Responses in three chimpanzees were compared following challenge with a clonal
      hepatitis C virus (HCV) contained in plasma from an animal that had received
      infectious RNA transcripts. Two of the chimpanzees (Ch1552 and ChX0186) had
      recovered from a previous infection with HCV, while the third (Ch1605) was a
      naive animal. All animals were challenged by reverse titration with decreasing
      dilutions of plasma and became serum RNA positive following challenge. Ch1605
      displayed a typical disease profile for a chimpanzee. We observed increasing
      levels of serum RNA from week 1 postinoculation (p.i.), reaching a peak of 10(6)
      copies/ml at week 9 p.i., and alanine aminotransferase (ALT) elevations and
      seroconversion to HCV antibodies at week 10 p.i. In contrast, both Ch1552 and
      ChX0186 exhibited much shorter periods of viremia (4 weeks), low serum RNA levels
      (peak, 10(3) copies/ml), and minimal ALT elevations. A comparison of intrahepatic
      cytokine levels in Ch1552 and Ch1605 showed greater and earlier gamma interferon
      (IFN-gamma) and tumor necrosis factor alpha responses in the previously infected
      animal, responses that were 30-fold greater than baseline responses at week 4
      p.i. for IFN-gamma in Ch1552 compared to 12-fold in Ch1605 at week 10 p.i. These
      data indicate (i) that clonal HCV generated from an infectious RNA transcript
      will lead to a typical HCV infection in naive chimpanzees, (ii) that there are
      memory immune responses in recovered chimpanzees that control HCV infection upon
      rechallenge, and (iii) that these responses seem to be T-cell mediated, as none
      of the animals had detectable antibody against the HCV envelope glycoproteins.
      These observations have encouraging implications for the development of a vaccine
      for HCV.

PMID- 12050372
TI  - Molecular characterization of VP6 genes of human rotavirus isolates: correlation
      of genogroups with subgroups and evidence of independent segregation.
AB  - A reverse transcription-PCR (RT-PCR) was established to amplify a 379-bp cDNA
      fragment (nucleotides 747 to 1126, coding for amino acids 241 to 367) of the VP6
      gene of group A rotaviruses associated with subgroup (SG) specificity. Thirty
      eight human rotavirus strains characterized with SG-specific monoclonal
      antibodies were subjected to VP6-specific RT-PCR, and PCR amplicons were used for
      sequencing. Nucleic acid sequencing and phylogenetic analysis of the VP6
      amplicons revealed two clusters, or genogroups. Two genetic lineages were
      distinguished within genogroup I, consisting of strains serologically
      characterized as SG I, and three genetic lineages were distinguished within
      genogroup II, composed of strains serologically characterized as SG II, SG I +
      II, and SG non-I, non-II. Subgrouping of rotaviruses by means of serological
      methods may result in strains not being assigned the correct SG or in a failure
      of strains to subgroup. Molecular characterization of the SG-defining region of
      VP6 provided evidence for independent segregation of the rotavirus genes encoding
      VP4, VP6, and VP7.

PMID- 12050373
TI  - Expansion of a CD28-intermediate subset among CD8 T cells in patients with
      infectious mononucleosis.
AB  - Infectious mononucleosis (IM) is an acute sporadic infection that usually affects
      young adults, and during infection a massive expansion of CD8 T cells is
      generally considered to occur. However, CD28 expression of the expanded cells has
      not been characterized. When peripheral blood mononuclear cells of acute IM (AIM)
      patients were analyzed by flow cytometry, a continuous spectrum of CD28 intensity
      ranging from negative to high, which could be separated into CD28 negative,
      intermediate (int), and positive, was seen for CD8 T cells. We studied 26 IM
      patients who were diagnosed on the basis of standard methods and found that all
      patients had the continuous CD28 spectrum. CD28 is a costimulatory molecule on T
      cells, and its expression is associated with the subdivision of CD8 cells into
      cytotoxic (CD28-positive) and suppressor (CD28-negative) T cells. After 24 h of
      ex vivo culturing, however, the continuous spectrum was found to consist of only
      CD28-positive and CD28-negative CD8 T cells, because the CD28-int cells had
      disappeared due to apoptosis. The CD28-int T cells have several cytotoxic
      functions, suggesting that CD28-int T cells are effectors. Examination of other
      costimulatory markers in AIM patients showed that CD80 and CD152 were not
      affected. In patients with other viral infections, such as measles or rubella,
      however, the continuous spectrum was not detected. These results suggest that
      there is an unusual CD28 expression pattern in patients with AIM, namely, the
      presence of a functional CD28-int subset among CD8 T cells. These findings are of
      special importance for clarifying the defense mechanism against Epstein-Barr
      virus infection, and the role of CD28 molecules in humans and should also be
      helpful for the diagnosis of AIM.

PMID- 12050374
TI  - Characterization of producer cell-dependent restriction of murine leukemia virus
      replication.
AB  - We previously reported that the human bronchocarcinoma cell line A549 produces
      poorly infectious gibbon ape leukemia virus-pseudotyped Moloney murine leukemia
      virus (MLV). In contrast, similar amounts of virions recovered from human
      fibrosarcoma HT1080 cells result in 10-fold-higher transduction rates (G. Duisit,
      A. Salvetti, P. Moullier, and F. Cosset, Hum. Gene Ther. 10:189-200, 1999). We
      have now extended this initial observation to other type-C envelope (Env)
      pseudotypes and analyzed the mechanism involved. Structural and morphological
      analysis showed that viral particles recovered from A549 (A549-MLV) and HT1080
      (HT1080-MLV) cells were normal and indistinguishable from each other. They
      expressed equivalent levels of mature Env proteins and bound similarly to the
      target cells. Furthermore, incoming particles reached the cytosol and directed
      the synthesis of linear viral DNA equally efficiently. However, almost no
      detectable circular DNAs could be detected in A549-MLV-infected cells, indicating
      that the block of infection resulted from defective nuclear translocation of the
      preintegration complex. Interestingly, pseudotyping of A549-MLV with vesicular
      stomatitis virus glycoprotein G restored the amount of circular DNA forms as well
      as the transduction rates to HT1080-MLV levels, suggesting that the postentry
      blockage could be overcome by endocytic delivery of the core particles downstream
      of the restriction point. Thus, in contrast to the previously described target
      cell-dependent Fv-1 (or Fv1-like) restriction in mammalian cells (P. Pryciak and
      H. E. Varmus, J. Virol. 66:5959-5966, 1992; G. Towers, M. Bock, S. Martin, Y.
      Takeuchi, J. P. Stoye, and O. Danos, Proc. Natl. Acad. Sci. USA 97:12295-12299,
      2000), we report here a new restriction of MLV replication that relies only on
      the producer cell type.

PMID- 12050375
TI  - Critical role for glial cells in the propagation and spread of lymphocytic
      choriomeningitis virus in the developing rat brain.
AB  - Inoculation of the neonatal rat with lymphocytic choriomeningitis virus (LCMV)
      results in the selective infection of several neuronal populations and in focal
      pathological changes. However, the pathway by which LCMV reaches the susceptible
      neurons has not been described, and the nature and time course of the
      pathological changes induced by the infection are largely unknown. This study
      examined the sequential migration of LCMV in the developing rat brain and
      compared the pathological changes among infected brain regions. The results
      demonstrate that astrocytes and Bergmann glia cells are the first cells of the
      brain parenchyma infected with LCMV and that the virus spreads across the brain
      principally via contiguous glial cells. The virus then spreads from glial cells
      into neurons. However, not all neurons are susceptible to infection. LCMV infects
      neurons in only four specific brain regions: the cerebellum, olfactory bulb,
      dentate gyrus, and periventricular region. The virus is then cleared from glial
      cells but persists in neurons. LCMV induces markedly different pathological
      changes in each of the four infected regions. The cerebellum undergoes an acute
      and permanent destruction, while the olfactory bulb is acutely hypoplastic but
      recovers fully with age. Neurons of the dentate gyrus are unaffected in the acute
      phase but undergo a delayed-onset mortality. In contrast, the periventricular
      region has neither acute nor late-onset cell loss. Thus, LCMV infects four
      specific brain regions in the developing brain by spreading from glial cells to
      neurons and then induces substantially different pathological changes with
      diverse time courses in each of the four infected regions.

PMID- 12050376
TI  - Targeting and hematopoietic suppression of human CD34+ cells by measles virus.
AB  - The major cause of mortality in measles is generalized suppression of cell
      mediated immunity that persists following virus clearance and results in
      secondary infections. The mechanisms contributing to this long-term
      immunosuppression are not clear. Herein we present evidence that measles virus
      (MV) disrupts hematopoiesis by infecting human CD34+ cells and human bone marrow
      stroma. MV infection does not affect the hematopoietic capability of
      hematopoietic stem cells (HSCs) directly; rather, the infection impairs the
      ability of stroma to support development of HSCs. These results suggest that MV
      mediated defects in hematopoiesis contribute to the long-term immunosuppression
      seen in measles.

PMID- 12050377
TI  - Antibodies to rotavirus outer capsid glycoprotein VP7 neutralize infectivity by
      inhibiting virion decapsidation.
AB  - The rotavirus capsid is composed of three concentric protein layers. Proteins VP4
      and VP7 comprise the outer layer. VP4 forms spikes, is the viral attachment
      protein, and is cleaved by trypsin into VP8* and VP5*. VP7 is a glycoprotein and
      the major constituent of the outer protein layer. Both VP4 and VP7 induce
      neutralizing and protective antibodies. To gain insight into the virus
      neutralization mechanisms, the effects of neutralizing monoclonal antibodies
      (MAbs) directed against VP8*, VP5*, and VP7 on the decapsidation process of
      purified OSU and RRV virions were studied. Changes in virion size were followed
      in real time by 90 degrees light scattering. The transition from triple-layered
      particles to double-layered particles induced by controlled low calcium
      concentrations was completely inhibited by anti-VP7 MAbs but not by anti-VP8* or
      anti-VP5* MAbs. The inhibitory effect of the MAb directed against VP7 was
      concentration dependent and was abolished by papain digestion of virus-bound
      antibody under conditions that generated Fab fragments but not under conditions
      that generated F(ab')(2) fragments. Electron microscopy showed that RRV virions
      reacted with an anti-VP7 MAb stayed as triple-layered particles in the presence
      of excess EDTA. Furthermore, the infectivity of rotavirus neutralized via VP8*,
      but not that of rotavirus neutralized via VP7, could be recovered by lipofection
      of neutralized particles into MA-104 cells. These data are consistent with the
      notion that antibodies directed at VP8* neutralize by inhibiting binding of virus
      to the cell. They also indicate that antibodies directed at VP7 neutralize by
      inhibiting virus decapsidation, in a manner that is dependent on the bivalent
      binding of the antibody.

PMID- 12050379
TI  - Construction and manipulation of an infectious clone of the bovine herpesvirus 1
      genome maintained as a bacterial artificial chromosome.
AB  - The complete genome of bovine herpesvirus 1 (BoHV-1) strain V155 has been cloned
      as a bacterial artificial chromosome (BAC). Following electroporation into
      Escherichia coli strain DH10B, the BoHV-1 BAC was stably propagated over multiple
      generations of its host. BAC DNA recovered from DH10B cells and transfected into
      bovine cells produced a cytopathic effect which was indistinguishable from that
      of the parent virus. Analysis of the replication kinetics of the viral progeny
      indicated that insertion of the BAC vector into the thymidine kinase gene did not
      affect viral replication. Specific manipulation of the BAC was demonstrated by
      deleting the gene encoding glycoprotein E by homologous recombination in DH10B
      cells facilitated by GET recombination. These studies illustrate that the
      propagation and manipulation of herpesviruses in bacterial systems will allow for
      rapid and accurate characterization of BoHV-1 genes. In turn, this will allow for
      the full utilization of BoHV-1 as a vaccine vector.

PMID- 12050378
TI  - Regulation of DNA-raised immune responses by cotransfected interferon regulatory
      factors.
AB  - Interferon regulatory factor 1 (IRF-1), IRF-3, and IRF-7 have been tested as
      genetic adjuvants for influenza virus hemagglutinin (HA) and nucleoprotein
      vaccine DNAs. Cotransfection of HA with IRF-3 and IRF-7 increased CD4 T-cell
      responses by 2- to 4-fold and CD8 T-cell responses by more than 10-fold.
      Following intramuscular deliveries of DNA, both CD4 and CD8 T cells were biased
      towards type 1 immune responses and the production of gamma interferon. Following
      gene gun bombardments of DNA, both were biased towards type 2 immune responses
      and the production of interleukin-4. The biases of the T-cell responses towards
      type 1 or type 2 were stronger for immunizations with IRF-3 as an adjuvant than
      for immunizations with IRF-7 as an adjuvant. Moderate adjuvant effects for
      antibody were observed. The isotypes of the antibody responses reflected the
      method of DNA delivery; intramuscular deliveries of DNA predominantly raised
      immunoglobulin G2a (IgG2a), whereas gene gun deliveries of DNA predominantly
      raised IgG1. These biases were enhanced by the codelivered IRFs. Overall, under
      the conditions of our experiments, IRF-3 had good activity for T cells, IRF-7 had
      good activity for both antibody and T cells, and IRF-1 had good activity for
      antibody.

PMID- 12050380
TI  - Cross-protection against challenge with Puumala virus after immunization with
      nucleocapsid proteins from different hantaviruses.
AB  - Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal
      syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N)
      is relatively conserved among hantaviruses and highly immunogenic in both
      laboratory animals and humans, and it has been shown to induce efficient
      protective immunity in animal models. To investigate the ability of recombinant N
      (rN) from different hantaviruses to elicit cross-protection, we immunized bank
      voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava
      (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized
      with PUUV and TOPV rN were completely protected. In the group immunized with DOBV
      rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in
      the group immunized with ANDV rN, which is more closely related to PUUV rN than
      DOBV rN. Humoral and cellular immune responses after rN immunization were also
      investigated. The highest cross-reactive humoral responses against PUUV antigen
      were detected in sera from ANDV rN-immunized animals, followed by those from TOPV
      rN-immunized animals, and only very low antibody cross-reactivity was observed in
      sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from
      animals immunized with all heterologous rNs were as efficiently recalled in vitro
      by PUUV rN as were T lymphocytes from animals immunized with homologous protein.
      In summary, this study has shown that hantavirus N can elicit cross-protective
      immune responses against PUUV, and the results suggest a more important role for
      the cellular arm of the immune response than for the humoral arm in cross
      protection elicited by rN.

PMID- 12050381
TI  - Characterization of the arenavirus RING finger Z protein regions required for Z
      mediated inhibition of viral RNA synthesis.
AB  - The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is an
      enveloped virus with a bisegmented negative-strand RNA genome whose proteomic
      capability is limited to four polypeptides, namely, nucleoprotein; surface
      glycoprotein (GP), which is proteolytically processed into GP1 and GP2;
      polymerase (L); and a small (11-kDa) RING finger protein (Z). Using a reverse
      genetic system based on the ARM strain of LCMV, we have previously shown that Z
      has a strong inhibitory activity on LCMV minigenome transcription and RNA
      replication (T. I. Cornu and J. C. de la Torre, J. Virol. 75:9415-9426, 2001). In
      the present study, we have identified regions and specific amino acid residues
      within Z which contribute to its inhibitory activity on RNA synthesis mediated by
      the LCMV polymerase. Z proteins from different LCMV strains had similar
      inhibitory activities on the expression of the LCMV ARM minigenome, whereas the Z
      protein of the genetically more distantly related Tacaribe virus had an
      approximately 10-fold lower inhibitory activity on ARM minigenome expression.
      Results from the use of chimera proteins between Z and Xenopus Neuralized, a
      nonviral RING finger protein, indicated that the structural integrity of the Z
      RING domain (RD) was required but not sufficient for the inhibitory activity of
      Z. Serial deletion mutants of the N and C termini of Z showed that the N terminus
      (residues 1 through 16) and C terminus (residues 79 through 90) do not contribute
      to the Z inhibitory activity. A highly conserved tryptophan (W) residue located
      at position 36 in ARM-Z, next to the second conserved cysteine (C) residue of the
      Z RD, also contributed to the Z inhibitory activity.

PMID- 12050382
TI  - Human immunodeficiency virus type 1 enters brain microvascular endothelia by
      macropinocytosis dependent on lipid rafts and the mitogen-activated protein
      kinase signaling pathway.
AB  - Brain microvascular endothelial cells (BMVECs) present an incomplete barrier to
      human immunodeficiency virus type 1 (HIV-1) neuroinvasion. In order to clarify
      the mechanisms of HIV-1 invasion, we have examined HIV-1 uptake and transcellular
      penetration in an in vitro BMVEC model. No evidence of productive infection was
      observed by luciferase, PCR, and reverse transcriptase assays. Approximately 1%
      of viral RNA and 1% of infectious virus penetrated the BMVEC barrier without
      disruption of tight junctions. The virus upregulated ICAM-1 on plasma membranes
      and in cytoplasmic vesiculotubular structures. HIV-1 virions were entangled by
      microvilli and were taken into cytoplasmic vesicles through surface invaginations
      without fusion of the virus envelope with the plasma membrane. Subsequently, the
      cytoplasmic vesicles fused with lysosomes, the virions were lysed, and the
      vesicles diminished in size. Upon cell entry, HIV-1 colocalized with cholera
      toxin B, which targets lipid raft-associated GM1 ganglioside. Cholesterol
      extracting agents, cyclodextrin and nystatin, and polyanion heparin significantly
      inhibited virus entry. Anti-CD4 had no effect and the chemokine AOP-RANTES had
      only a slight inhibitory effect on virus entry. HIV-1 activated the mitogen
      activated protein kinase (MAPK) pathway, and inhibition of MAPK/Erk kinase
      inhibited virus entry. Entry was also blocked by dimethylamiloride, indicating
      that HIV-1 enters endothelial cells by macropinocytosis. Therefore, HIV-1
      penetrates BMVECs in ICAM-1-lined macropinosomes by a mechanism involving lipid
      rafts, MAPK signaling, and glycosylaminoglycans, while CD4 and chemokine
      receptors play limited roles in this process.

PMID- 12050383
TI  - Asymmetric requirement for cholesterol in receptor-bearing but not envelope
      bearing membranes for fusion mediated by ecotropic murine leukemia virus.
AB  - We show that fusion mediated by ecotropic murine leukemia virus envelope is
      dependent on cholesterol in receptor-bearing membranes. The effect is >10 times
      larger in insect cells than mammalian cells, probably because the former can be
      more extensively depleted of cholesterol. The fact that cholesterol is apparently
      not needed in envelope-bearing membranes suggests that it plays a role in an
      asymmetric step in membrane fusion and argues against a class of models in which
      cholesterol is important in symmetric fusion intermediates. The insect cell
      system has promise for clarifying the role of membrane rafts in other aspects of
      cell physiology.

PMID- 12050384
TI  - Polarized release of human cytomegalovirus from placental trophoblasts.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous infectious pathogen that, when
      transmitted to the fetus in utero, can result in numerous sequelae, including
      late-onset sensorineural damage. The villous trophoblast, the cellular barrier
      between maternal blood and fetal tissue in the human placenta, is infected by
      HCMV in vivo. Primary trophoblasts cultured on impermeable surfaces can be
      infected by HCMV, but release of progeny virus is delayed and minimal. It is not
      known whether these epithelial cells when fully polarized can release HCMV and,
      if so, if release is from the basal membrane surface toward the fetus. We
      therefore ask whether, and in which direction, progeny virus release occurs from
      HCMV-infected trophoblasts cultured on semipermeable (3.0-microm-pore-size)
      membranes that allow functional polarization. We show that infectious HCMV
      readily diffuses across cell-free 3.0-microm-pore-size membranes and that apical
      infection of confluent and multilayered trophoblasts cultured on these membranes
      reaches cells at the membrane surface. Using two different infection and culture
      protocols, we found that up to 20% of progeny virus is released but that <1% of
      released virus is detected in the basal culture chamber. These results suggest
      that very little, if any, HCMV is released from an infected villous trophoblast
      into the villous stroma where the virus could ultimately infect the fetus.

PMID- 12050385
TI  - Identification and characterization of the UL56 gene product of herpes simplex
      virus type 2.
AB  - The UL56 gene product of herpes simplex virus (HSV) has been shown to play an
      important role in viral pathogenicity. However, the properties and functions of
      the UL56 protein are little understood. We raised rabbit polyclonal antisera
      specific for the UL56 protein of HSV type 2 (HSV-2) and examined its expression
      and properties. The gene product was identified as three polypeptides with
      apparent molecular masses ranging from 32 to 35 kDa in HSV-2-infected cells, and
      at least one species was phosphorylated. Studies of their origins showed that the
      UL56 protein of HSV-2 is also translated from the upstream in-frame methionine
      codon that is not present in the HSV-1 genome. Synthesis was first detected at 6
      h postinfection and was not abolished by the viral DNA synthesis inhibitor
      phosphonoacetic acid. Indirect immunofluorescence studies revealed that the UL56
      protein localized to both the Golgi apparatus and cytoplasmic vesicles in HSV-2
      infected and single UL56-expressing cells. Deletion mutant analysis showed that
      the C-terminal hydrophobic region of the protein was required for association
      with the cytoplasmic membrane and that the N-terminal proline-rich region was
      important for its translocation to the Golgi apparatus and cytoplasmic vesicles.
      Moreover, the results of protease digestion assays and sucrose gradient
      fractionation strongly suggested that UL56 is a tail-anchored type II membrane
      protein associated with lipid rafts. We thus hypothesized that the UL56 protein,
      as a tail-anchored type II membrane protein, may be involved in vesicular
      trafficking in HSV-2-infected cells.

PMID- 12050386
TI  - The UL48 tegument protein of pseudorabies virus is critical for intracytoplasmic
      assembly of infectious virions.
AB  - The pseudorabies virus (PrV) homolog of the tegument protein encoded by the UL48
      gene of herpes simplex virus type 1 (HSV-1) was identified by using a
      monospecific rabbit antiserum against a bacterial fusion protein. UL48-related
      polypeptides of 53, 55, and 57 kDa were detected in Western blots of infected
      cells and purified virions. Immunofluorescence studies demonstrated that the PrV
      UL48 protein is predominantly localized in the cytoplasm but is also found in the
      nuclei of infected cells. Moreover, it is a constituent of extracellular virus
      particles but is absent from primary enveloped perinuclear virions. In
      noncomplementing cells, a UL48-negative PrV mutant (PrV-DeltaUL48) exhibited
      delayed growth and significantly reduced plaque sizes and virus titers,
      deficiencies which were corrected in UL48-expressing cells. RNA analyses
      indicated that, like its HSV-1 homolog, the PrV UL48 protein is involved in
      regulation of immediate-early gene expression. However, the most salient effect
      of the UL48 gene deletion was a severe defect in virion morphogenesis. Late after
      infection, electron microscopy of cells infected with PrV-DeltaUL48 revealed
      retention of newly formed nucleocapsids in the cytoplasm, whereas enveloped
      intracytoplasmic or extracellular complete virions were only rarely observed. In
      contrast, capsidless particles were produced and released in great amounts.
      Remarkably, the intracytoplasmic capsids were labeled with antibodies against the
      UL36 and UL37 tegument proteins, whereas the capsidless particles were labeled
      with antisera directed against the UL46, UL47, and UL49 tegument proteins. These
      findings suggested that the UL48 protein is involved in linking capsid and future
      envelope-associated tegument proteins during virion formation. Thus, like its HSV
      1 homolog, the UL48 protein of PrV functions in at least two different steps of
      the viral life cycle. The drastic inhibition of virion formation in the absence
      of the PrV UL48 protein indicates that it plays an important role in virion
      morphogenesis prior to secondary envelopment of intracytoplasmic nucleocapsids.
      However, the UL48 gene of PrV is not absolutely essential, and concomitant
      deletion of the adjacent tegument protein gene UL49 also did not abolish virus
      replication in cell culture.

PMID- 12050387
TI  - SLAM (CD150)-independent measles virus entry as revealed by recombinant virus
      expressing green fluorescent protein.
AB  - Wild-type measles virus (MV) strains use human signaling lymphocyte activation
      molecule (SLAM) as a cellular receptor, while vaccine strains such as the
      Edmonston strain can use both SLAM and CD46 as receptors. Although the expression
      of SLAM is restricted to cells of the immune system (lymphocytes, dendritic
      cells, and monocytes), histopathological studies with humans and experimentally
      infected monkeys have shown that MV also infects SLAM-negative cells, including
      epithelial, endothelial, and neuronal cells. In an attempt to explain these
      findings, we produced the enhanced green fluorescent protein (EGFP)-expressing
      recombinant MV (IC323-EGFP) based on the wild-type IC-B strain. IC323-EGFP showed
      almost the same growth kinetics as the parental recombinant MV and produced large
      syncytia exhibiting green autofluorescence in SLAM-positive cells. Interestingly,
      all SLAM-negative cell lines examined also showed green autofluorescence after
      infection with IC323-EGFP, although the virus hardly spread from the originally
      infected individual cells and thus did not induce syncytia. When the number of
      EGFP-expressing cells after infection was taken as an indicator, the
      infectivities of IC323-EGFP for SLAM-negative cells were 2 to 3 logs lower than
      those for SLAM-positive cells. Anti-MV hemagglutinin antibody or fusion block
      peptide, but not anti-CD46 antibody, blocked IC323-EGFP infection of SLAM
      negative cells. This infection occurred under conditions in which entry via
      endocytosis was inhibited. These results indicate that MV can infect a variety of
      cells, albeit with a low efficiency, by using an as yet unidentified receptor(s)
      other than SLAM or CD46, in part explaining the observed MV infection of SLAM
      negative cells in vivo.

PMID- 12050388
TI  - Human herpesvirus 6 variant A but not variant B induces fusion from without in a
      variety of human cells through a human herpesvirus 6 entry receptor, CD46.
AB  - Human herpesvirus 6 (HHV-6) is a lymphotropic betaherpesvirus that productively
      infects T cells and monocytes. HHV-6 isolates can be differentiated into two
      groups, variants A and B (HHV-6A and HHV-6B). Here, we show a functional
      difference between HHV-6A and -6B in that HHV-6A induced syncytium formation of
      diverse human cells but HHV-6B did not. The syncytium formation induced by HHV-6A
      was observed 2 h after infection; moreover, it was found in the presence of
      cycloheximide, indicating that HHV-6A induced fusion from without (FFWO) in the
      target cells. Furthermore, the fusion event was dependent on the expression of
      the HHV-6 entry receptor, CD46, on the target cell membrane. In addition, we
      determined that short consensus repeat 2 (SCR2), -3, and -4 of the CD46
      ectodomain were essential for the formation of the virus-induced syncytia.
      Monoclonal antibodies against glycoproteins B and H of HHV-6A inhibited the
      fusion event, indicating that the syncytium formation induced by HHV-6A required
      glycoproteins H and B. These findings suggest that FFWO, which HHV-6A induced in
      a variety of cell lines, may play an important role in the pathogenesis of HHV
      6A, not only in lymphocytes but also in various tissues, because CD46 is
      expressed ubiquitously in human tissues.

PMID- 12050390
TI  - A mutation in the latency-related gene of bovine herpesvirus 1 disrupts the
      latency reactivation cycle in calves.
AB  - Bovine herpesvirus 1 (BHV-1) is an important pathogen of cattle, and infection is
      usually initiated via the ocular or nasal cavity. Following acute infection, the
      primary site for BHV-1 latency is the sensory neuron. Reactivation from latency
      occurs sporadically, resulting in virus shedding and transmission to uninfected
      cattle. The only abundant viral transcript expressed during latency is the
      latency-related (LR) RNA, suggesting that it mediates some aspect of latency. An
      LR mutant was constructed by inserting three stop codons near the beginning of
      the LR-RNA, suggesting that expression of LR proteins would be altered. The LR
      mutant grew with wild-type (wt) efficiency in bovine kidney cells (MDBK). When
      calves were infected with the LR mutant, a dramatic decrease (3 to 4 logs) in
      ocular, but not nasal, viral shedding occurred during acute infection relative to
      the wt or the LR-rescued virus (M. Inman, L. Lovato, A. Doster, and C. Jones, J.
      Virol. 75:8507-8515, 2001). In this study, we examined the latency reactivation
      cycle in calves infected with the LR mutant and compared these results to those
      from calves infected with wt BHV-1 or the LR-rescued virus. During acute
      infection, lower levels of infectious virus were detected in trigeminal ganglion
      homogenates from calves infected with the LR mutant. As judged by in situ
      hybridization, BHV-1-positive neurons were detected in trigeminal ganglia of
      calves infected with the wt but not the LR mutant. Although LR-RNA was detected
      by reverse transcription-PCR in calves latently infected with the LR mutant, a
      semiquantitative PCR analysis revealed that lower levels of viral DNA were
      present in trigeminal ganglia of calves infected with the LR mutant.
      Dexamethasone treatment of calves latently infected with wt BHV-1 or the LR
      rescued virus, but not the LR mutant, consistently induced reactivation from
      latency, as judged by shedding of infectious virus from the nose or eyes and
      increases in BHV-1-specific antibodies. In summary, this study demonstrates that
      wt expression of LR gene products plays an important role in the latency
      reactivation cycle of BHV-1 in cattle.

PMID- 12050389
TI  - Cell type-specific replication of simian virus 40 conferred by hormone response
      elements in the late promoter.
AB  - The late genes of SV40 are not expressed at significant levels until after the
      onset of viral DNA replication. We previously identified two hormone response
      elements (HREs) in the late promoter that contribute to this delay. Mutants
      defective in these HREs overexpress late RNA at early, but not late, times after
      transfection of CV-1PD cells. Overexpression of nuclear receptors (NRs) that
      recognize these HREs leads to repression of the late promoter in a sequence
      specific and titratable manner, resulting in a delay in late gene expression.
      These observations led to a model in which the late promoter is repressed at
      early times after infection by NRs, with this repression being relieved by
      titration of these repressors through simian virus 40 (SV40) genome replication
      to high copy number. Here, we tested this model in the context of the viral life
      cycle. SV40 genomes containing mutations in either or both HREs that
      significantly reduce NR binding without altering the coding of any proteins were
      constructed. Competition for replication between mutant and wild-type viruses in
      low-multiplicity coinfections indicated that the +1 HRE offered a significant
      selective advantage to the virus within a few cycles of infection in African
      green monkey kidney cell lines CV-1, CV-1P, TC-7, MA-134, and Vero but not in CV
      1PD' cells. Interestingly, the +55 HRE offered a selective disadvantage in MA-134
      cells but had no effect in CV-1, CV-1P, TC-7, Vero, and CV-1PD' cells. Thus, we
      conclude that these HREs are biologically important to the virus, but in a cell
      type-specific manner.

PMID- 12050391
TI  - Dissection of human immunodeficiency virus type 1 entry with neutralizing
      antibodies to gp41 fusion intermediates.
AB  - Human immunodeficiency virus type 1 (HIV-1) entry requires conformational changes
      in the transmembrane subunit (gp41) of the envelope glycoprotein (Env) involving
      transient fusion intermediates that contain exposed coiled-coil (prehairpin) and
      six-helix bundle structures. We investigated the HIV-1 entry mechanism and the
      potential of antibodies targeting fusion intermediates to block Env-mediated
      membrane fusion. Suboptimal temperature (31.5 degrees C) was used to prolong
      fusion intermediates as monitored by confocal microscopy. After transfer to 37
      degrees C, these fusion intermediates progressed to syncytium formation with
      enhanced kinetics compared with effector-target (E/T) cell mixtures that were
      incubated only at 37 degrees C. gp41 peptides DP-178, DP-107, and IQN17 blocked
      fusion more efficiently (5- to 10-fold-lower 50% inhibitory dose values) when
      added to E/T cells at the suboptimal temperature prior to transfer to 37 degrees
      C. Rabbit antibodies against peptides modeling the N-heptad repeat or the six
      helix bundle of gp41 blocked fusion and viral infection at 37 degrees C only if
      preincubated with E/T cells at the suboptimal temperature. Similar fusion
      inhibition was observed with human six-helix bundle-specific monoclonal
      antibodies. Our data demonstrate that antibodies targeting gp41 fusion
      intermediates are able to bind to gp41 and arrest fusion. They also indicate that
      six-helix bundles can form prior to fusion and that the lag time before fusion
      occurs may include the time needed to accumulate preformed six-helix bundles at
      the fusion site.

PMID- 12050392
TI  - Long-term circulation of vaccine-derived poliovirus that causes paralytic
      disease.
AB  - Successful implementation of the global poliomyelitis eradication program raises
      the problem of vaccination against poliomyelitis in the posteradication era. One
      of the options under consideration envisions completely stopping worldwide the
      use of the Sabin vaccine. This strategy is based on the assumption that the
      natural circulation of attenuated strains and their derivatives is strictly
      limited. Here, we report the characterization of a highly evolved derivative of
      the Sabin vaccine strain isolated in a case of paralytic poliomyelitis from a 7
      month-old immunocompetent baby in an apparently adequately immunized population.
      Analysis of the genome of this isolate showed that it is a double (type 1-type 2
      type 1) vaccine-derived recombinant. The number of mutations accumulated in both
      the type 1-derived and type 2-derived portions of the recombinant genome suggests
      that both had diverged from their vaccine predecessors approximately 2 years
      before the onset of the illness. This fact, along with other recent observations,
      points to the possibility of long-term circulation of Sabin vaccine strain
      derivatives associated with an increase in their neurovirulence. Comparison of
      genomic sequences of this and other evolved vaccine-derived isolates reveals some
      general features of natural poliovirus evolution. They include a very high
      preponderance and nonrandom distribution of synonymous substitutions,
      conservation of secondary structures of important cis-acting elements of the
      genome, and an apparently adaptive character of most of the amino acid mutations,
      with only a few of them occurring in the antigenic determinants. Another
      interesting feature is a frequent occurrence of tripartite intertypic
      recombinants with either type 1 or type 3 homotypic genomic ends.

PMID- 12050393
TI  - Identification of NF-kappaB-dependent gene networks in respiratory syncytial
      virus-infected cells.
AB  - Respiratory syncytial virus (RSV) is a mucosa-restricted virus that is a leading
      cause of epidemic respiratory tract infections in children. In epithelial cells,
      RSV replication activates nuclear translocation of the inducible transcription
      factor nuclear factor kappaB (NF-kappaB) through proteolysis of its cytoplasmic
      inhibitor, IkappaB. In spite of a putative role in mediating virus-inducible gene
      expression, the spectrum of NF-kappaB-dependent genes induced by RSV infection
      has not yet been determined. To address this, we developed a tightly regulated
      cell system expressing a nondegradable, epitope-tagged IkappaBalpha isoform (Flag
      IkappaBalpha Mut) whose expression could be controlled by exogenous addition of
      nontoxic concentrations of doxycycline. Flag-IkappaBalpha Mut expression potently
      inhibited IkappaBalpha proteolysis, NF-kappaB binding, and NF-kappaB-dependent
      gene transcription in cells stimulated with the prototypical NF-kappaB-activating
      cytokine tumor necrosis factor alpha (TNF-alpha) and in response to RSV
      infection. High-density oligonucleotide microarrays were then used to profile
      constitutive and RSV-induced gene expression in the absence or presence of Flag
      IkappaBalpha Mut. Comparison of these profiles revealed 380 genes whose
      expression was significantly changed by the dominant-negative NF-kappaB. Of
      these, 236 genes were constitutive (not RSV regulated), and surprisingly, only
      144 genes were RSV regulated, representing numerically approximately 10% of the
      total population of RSV-inducible genes at this time point. Hierarchical
      clustering of the 144 RSV- and Flag-IkappaBalpha Mut-regulated genes identified
      two discrete gene clusters. The first group had high constitutive expression, and
      its expression levels fell in response to RSV infection. In this group,
      constitutive mRNA expression was increased by Flag-IkappaBalpha Mut expression,
      and the RSV-induced decrease in expression was partly inhibited. In the second
      group, constitutive expression was very low (or undetectable) and, after RSV
      infection, expression levels strongly increased. In this group, NF-kappaB was
      required for RSV-inducible expression because Flag-IkappaBalpha Mut expression
      blocked their induction by RSV. This latter cluster includes chemokines,
      transcriptional regulators, intracellular proteins regulating translation and
      proteolysis, and secreted proteins (complement components and growth factor
      regulators). These data suggest that NF-kappaB action induces global cellular
      responses after viral infection.

PMID- 12050395
TI  - Interleukin-1beta expression in human gastric carcinoma with Epstein-Barr virus
      infection.
AB  - The KT tumor is a transplantable strain of a human Epstein-Barr virus (EBV)
      associated gastric carcinoma (EBVaGC), established in severe combined
      immunodeficiency (SCID) mice, with which the cytokine expression of EBVaGC can be
      investigated without interference from the infiltrating lymphocytes. As a part of
      a high-density oligonucleotide array (GeneChip) analysis of EBVaGC, the
      interleukin-1beta (IL-1beta) gene was the only cytokine gene that showed markedly
      higher expression in the KT tumor cells than in two tumor strains of EBV-negative
      GC. The results were confirmed by Northern blotting, Western blotting, and enzyme
      linked immunosorbent assay. Furthermore, we demonstrated a positive signal for IL
      1beta mRNA in the carcinoma cells of a surgically resected EBVaGC, but not in EBV
      negative GC, by in situ hybridization. In vitro, IL-1beta increased the cell
      growth of a GC cell line, TMK1. Thus, IL-1beta may act as an autocrine growth
      factor in EBVaGC.

PMID- 12050394
TI  - P0 of beet Western yellows virus is a suppressor of posttranscriptional gene
      silencing.
AB  - Higher plants employ a homology-dependent RNA-degradation system known as
      posttranscriptional gene silencing (PTGS) as a defense against virus infection.
      Several plant viruses are known to encode proteins that can suppress PTGS. Here
      we show that P0 of beet western yellows virus (BWYV) displays strong silencing
      suppressor activity in a transient expression assay based upon its ability to
      inhibit PTGS of green fluorescent protein (GFP) when expressed in agro
      infiltrated leaves of Nicotiana benthamiana containing a GFP transgene. PTGS
      suppressor activity was also observed for the P0s of two other poleroviruses,
      cucurbit aphid-borne yellows virus and potato leafroll virus. P0 is encoded by
      the 5'-proximal gene in BWYV RNA but does not accumulate to detectable levels
      when expressed from the genome-length RNA during infection. The low accumulation
      of P0 and the resulting low PTGS suppressor activity are in part a consequence of
      the suboptimal translation initiation context of the P0 start codon in viral RNA,
      although other factors, probably related to the viral replication process, also
      play a role. A mutation to optimize the P0 translation initiation efficiency in
      BWYV RNA was not stable during virus multiplication in planta. Instead, the P0
      initiation codon in the progeny was frequently replaced by a less efficient
      initiation codon such as ACG, GTG, or ATA, indicating that there is selection
      against overexpression of P0 from the viral genome.

PMID- 12050396
TI  - The human cytomegalovirus US8 glycoprotein binds to major histocompatibility
      complex class I products.
AB  - Human cytomegalovirus US8 is a type I membrane protein that partially colocalizes
      with cellular endosomal and lysosomal proteins. Although US8 does not have
      discernible effects on the processing and cell surface distribution of major
      histocompatibility complex (MHC) class I products, we have demonstrated that US8
      binds to MHC class I heavy chains in the endoplasmic reticulum.

PMID- 12050397
TI  - A mutation in the 3' region of the human immunodeficiency virus type 1 reverse
      transcriptase (Y318F) associated with nonnucleoside reverse transcriptase
      inhibitor resistance.
AB  - The Y318F substitution in the 3' region of human immunodeficiency virus type 1
      (HIV-1) reverse transcriptase (RT) has been linked to nonnucleoside RT inhibitor
      (NNRTI) resistance in vitro. A systematic search of a large phenotypic-genotypic
      database (Virco) linked the Y318F substitution with a >10-fold decrease in NNRTI
      susceptibility in >85% of clinically derived isolates. There was a significant
      association between Y318F and use of delavirdine (P = 10(-11)) and nevirapine (P
      = 10(-6)) but not efavirenz (P = 0.3). Site-directed HIV-1 Y318F mutants in an
      HXB2 background displayed 42-fold-decreased susceptibility to delavirdine but <3
      fold-decreased susceptibility to nevirapine or efavirenz. Combinations of Y318F
      with K103N, Y181C, or both resulted in decreased efavirenz susceptibility of 43-,
      3.3-, and 84-fold, respectively, as well as >100- and >60-fold decreases in
      delavirdine and nevirapine susceptibility, respectively. These results indicate
      the importance of the Y318F substitution in HIV-1 drug resistance.

PMID- 12050398
TI  - C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis
      and in trans.
AB  - Ebola virus is a highly lethal pathogen responsible for several outbreaks of
      hemorrhagic fever. Here we show that the primate lentiviral binding C-type
      lectins DC-SIGN and L-SIGN act as cofactors for cellular entry by Ebola virus.
      Furthermore, DC-SIGN on the surface of dendritic cells is able to function as a
      trans receptor, binding Ebola virus-pseudotyped lentiviral particles and
      transmitting infection to susceptible cells. Our data underscore a role for DC
      SIGN and L-SIGN in the infective process and pathogenicity of Ebola virus
      infection.

PMID- 12050399
TI  - A tyrosine-based motif in the cytoplasmic tail of pseudorabies virus glycoprotein
      B is important for both antibody-induced internalization of viral glycoproteins
      and efficient cell-to-cell spread.
AB  - Pseudorabies virus (PRV), a swine alphaherpesvirus, is capable of causing viremia
      in vaccinated animals. Two mechanisms that may help PRV avoid recognition by the
      host immune system during this viremia are direct cell-to-cell spread in tissue
      and antibody-induced internalization of viral cell surface glycoproteins in PRV
      infected blood monocytes, the carrier cells of the virus in the blood. PRV
      glycoprotein B (gB) is crucial during both processes. Here we show that mutating
      a tyrosine residue located in a YXXPhi motif in the gB cytoplasmic tail results
      in decreased efficiency of cell-to-cell spread and a strong reduction in antibody
      induced internalization of viral cell surface glycoproteins. Mutating the
      dileucine motif in the gB tail led to an increased cell-to-cell spread of the
      virus and the formation of large syncytia.

PMID- 12050404
TI  - Hexaaquadodeca-mu-bromo-octahedro-hexatantalum bromide chloride octahydrate.
AB  - The title compound, [Ta(6)Br(12)(H(2)O)(6)](Br(0.4)Cl(1.6)) x 8H(2)O,
      crystallizes in space group P 1 macro. The structure contains two
      crystallographically independent [Ta(6)Br(12)(H(2)O)(6)](2+) cluster cations
      forming distinct layers parallel to the ab plane. The compound is
      isoconfigurational with the double salts [Ta(6)Br(12)(H(2)O)(6)]X(2) x trans
      [Ta(6)Br(12)(OH)(4)(H(2)O)(2)] x 18H(2)O (X = Cl, Br).

PMID- 12050400
TI  - Bacterial superantigen exposure after resolution of influenza virus infection
      perturbs the virus-specific memory CD8(+)-T-cell repertoire.
AB  - Heterologous viral infections have been shown to impact the preexisting memory
      CD8(+)-T-cell repertoire. Bacterial superantigens are products of common human
      pathogenic bacteria, including staphylococci and streptococci, that are potent T
      cell-stimulatory molecules. In this report, we show that exposure to
      staphylococcal enterotoxin B, a bacterial superantigen, causes a selective
      functional deletion of cross-reactive influenza virus-specific CD8(+) memory T
      cells. This perturbation of the memory repertoire can have a significant impact
      on viral clearance after secondary challenge.

PMID- 12050405
TI  - Dilithium barium diphosphate.
AB  - The crystal structure of the novel title diphosphate, Li(2)BaP(2)O(7), exists
      with a three-dimensional lattice composed of BaO(9) polyhedra linked to corner-
      and edge-sharing P(2)O(7) diphosphate groups, forming layers parallel to the
      (010) plane, the layers being linked by P[bond]O[bond]Ba bridges. Tunnels thus
      created between the layers are occupied by Li(+) cations, two of which lie on
      twofold axes.

PMID- 12050406
TI  - NaMn(6)(P(2)O(7))(2)(P(3)O(10)) and KCd(6)(P(2)O(7))(2)(P(3)O(10)).
AB  - The crystal structures of two new diphosphates, sodium hexamanganese
      bis(diphosphate) triphosphate, NaMn(6)(P(2)O(7))(2)(P(3)O(10)), and potassium
      hexacadmium bis(diphosphate) triphosphate, KCd(6)(P(2)O(7))(2)(P(3)O(10)),
      confirm the rigidity of the M(6)(P(2)O(7))(2)(P(3)O(10)) matrix (M is Mn or Cd)
      and the relatively fixed dimensions of the tunnels extending in the a direction
      of the unit cell. The compounds are isomorphous; the P(2)O(7)(4-) anion and the
      alkali metal cations lie on mirror planes. Bond-valence analysis of the bonding
      details of the atoms found within the tunnels permits a prediction of the
      conductivity.

PMID- 12050401
TI  - Nef enhances human immunodeficiency virus type 1 infectivity in the absence of
      matrix.
AB  - Nef enhances the serine phosphorylation of the human immunodeficiency virus type
      1 matrix (MA) protein, which suggests that MA may be a functional target of Nef.
      Using mutants that remain infectious despite the absence of most or all of MA, we
      show in the present study that the ability of Nef to enhance virus infectivity is
      not compromised even if MA is entirely replaced by a heterologous lipid anchor.

PMID- 12050407
TI  - KZn(HP(2)O(7)) x 2H(2)O and KMn(HP(2)O(7)) x -2H(2)O: acidpyrophosphate
      metallates(II) with layer structures.
AB  - The crystal structures of the isomorphous title compounds, namely potassium zinc
      hydrogen pyrophosphate dihydrate and potassium manganese hydrogen pyrophosphate
      dihydrate, consist of acidic pyrophosphate-metallate(II) layers joined by K(+)
      ions and hydrogen-bridging bonds. The Zn(2+)/Mn(2+) ions are octahedrally
      surrounded by four pyrophosphate O atoms and by two water molecules. The
      (HP(2)O(7))(3-) anions exhibit eclipsed conformations. The metal ions and water O
      atoms lie on mirror planes, as does the central O atom of the (HP(2)O(7))(3-)
      anion.

PMID- 12050408
TI  - Synthetic hydrocerussite, 2PbCO(3) x Pb(OH)(2), by X-ray powder diffraction.
AB  - Synthetic hydrocerussite [trilead dihydroxide dicarbonate,
      Pb(3)(CO(3))(2)(OH)(2)] can be easily obtained, as a white powder, by the action
      of carbon dioxide and water on either lead or litharge at pH 4-5. This compound
      is also found in lead corrosion technological products as a fine-grained phase.
      Ab initio crystal structure determination was carried out on X-ray powder
      diffraction data. The heavy-atom method and the Patterson function helped
      determine the crystallographic model and the atom locations. The Rietveld fitting
      procedure was used for the final refinement. The atomic arrangement is closely
      related to the structures of other lead hydroxide carbonates. The hydrocerussite
      structure can be viewed as a sequence of two types of layers stacked along [001].
      Layer A is composed of Pb and CO(3), and layer B is composed of Pb and OH. The
      stacking sequence is ...BAABAA...

PMID- 12050409
TI  - K(2)SrNb(6)Cl(18), dipotassium strontium hexaniobium octadecachloride.
AB  - The structure of dipotassium strontium hexaniobium octadecachloride is based on
      [Nb(6)Cl(i)(12)Cl(a)(6)](4-) units (i and a denote 'inner' and 'outer' ligands,
      respectively), which have crystallographically imposed -3 symmetry, linked
      together by K(+) and Sr(2+) cations. The K(+) cation occupies a tetrahedral site
      in the face-centered cubic lattice of cluster units, and is bonded to 12 Cl
      ligands. The Sr atom is located in an octahedral site and is bonded to six outer
      Cl ligands.

PMID- 12050410
TI  - Aqua(4,4'-oxydibenzoato-kappa O)cadmium(II).
AB  - The Cd atom in the polymeric title compound, [Cd(C(14)H(8)O(5))(H(2)O)](n), is
      linked to four carboxyl O atoms and a water molecule in a five-coordinate
      coordination polyhedron that is midway between a square pyramid and a trigonal
      bipyramid. The Cd atom and the water molecules both lie on the same twofold axis
      and the central O atom of the 4,4'-oxydibenzoate moiety lies on another twofold
      axis. Covalent Cd-O bonds lead to the formation of a layer architecture
      perpendicular to the twofold axis, the layers being held together by hydrogen
      bonds in the third direction.

PMID- 12050411
TI  - A cyano-bridged dinuclear 4f-3d array.
AB  - A cyano-bridged bimetallic 4f-3d complex, triaqua-1 kappa(3)O-mu-cyano-1:2
      kappa(2)N:C-pentacyano-2 kappa(5)C-tetrakis(2-pyrrolidone-1 kappa
      O)chromium(III)dysprosium(III) dihydrate, [CrDy(C(4)H(7)NO)(4)(CN)(6)(H(2)O)(3)]
      x 2H(2)O, has been prepared and characterized by X-ray crystallographic analysis.
      The structure consists of a neutral cyano-bridged Dy-Cr dimer. A hydrogen-bonded
      three-dimensional architecture is formed through N[bond]H...O, O[bond]H...N and
      O[bond]H...O hydrogen bonds.

PMID- 12050412
TI  - Low-dimensional compounds containing cyano groups. II. catena-Poly[[(2,2'
      bipyridine-kappa(2)N:N')(dicyanamido-kappa N)copper(II)]-mu-dicyanamido
      kappa(2)N:N'].
AB  - The crystal structure of the title compound, [Cu(C(2)N(3))(2)(C(10)H(8)N(2))](n),
      is formed by neutral zigzag chains of the [-NC-N-CN-Cu[(bpy)N(CN)(2)]-NC-N-CN-]
      type running along the c axis (bpy is 2,2'-bipyridine). The Cu atoms in the
      chains are pentacoordinated in the form of a distorted tetragonal pyramid, with a
      CuN(5) chromophore. The coordination sites are occupied by two N atoms of one bpy
      molecule in the basal plane [Cu-N 2.018 (4) and 2.025 (2) A] and by three
      terminal N atoms of two dicyanamide ligands. One of the dicyanamide ligands is
      coordinated in a monodentate fashion through a nitrile N atom in the basal plane
      [Cu-N 1.963 (4) A]. The second acts as an end-to-end bridging ligand to a
      neighbouring Cu atom and is coordinated by one nitrile N atom in the basal plane
      [Cu-N 2.001 (2) A], while the second nitrile N atom occupies the apical position
      [Cu-N 2.159 (2) A] and originates from the bridge connecting another Cu atom. The
      shortest intrachain Cu.Cu distance is 8.212 (1) A, as a consequence of the large
      bridging ligand, whereas the minimum interchain distance between Cu atoms is only
      5.77 (7) A, because of the interdigitation of the chains.

PMID- 12050413
TI  - New structures in the bipyridine-copper(II) nitrate-methanol system:
      [(bpy)(2)Cu(NO(3))]NO(3) x CH(3)OH and [(bpy)(2)Cu(NO(3))]NO(3).
AB  - Reaction of 2,2'-bipyridine (bpy) and copper(II) nitrate in methanol results in
      two complexes, namely light-blue bis(2,2'-bipyridine)nitratocopper(II) nitrate
      methanol solvate, [Cu(NO(3))(C(10)H(8)N(2))(2)]NO(3) x CH(3)OH, (I), which is
      unstable in air, and the product of its decomposition, catena-poly[[[bis(2,2'
      bipyridine)copper(II)]-mu-nitrato-O:O'] nitrate],
      [[Cu(NO(3))(C(10)H(8)N(2))(2)]NO(3)](n), (II). The crystal structures of both
      compounds were determined from one crystal at room temperature. Later, the
      structure of (I) was redetermined at low temperature. In (I) and (II), the Cu
      atom is coordinated by two bpy and one or two nitrate ions, respectively. The
      second nitrate ion in (I), along with the methanol solvent molecule, is found in
      the outer coordination sphere, not bonded to Cu. The nitrate in (I) is chelating,
      while in (II), it bridges (bpy)(2)Cu complexes, forming a one-dimensional chain
      structure. The Cu cation in (II) lies on a twofold axis and the uncoordinated
      NO(3)(-) ion is located close to a twofold axis and is therefore disordered.
      Compound (I) converts into (II) upon loss of solvent.

PMID- 12050414
TI  - catena-Poly[[tri-n-butyltin]-mu-N-(1-naphthyl)maleamato].
AB  - The crystal structure of catena-poly[[tri-n-butyltin]-mu-3-(1
      naphthylaminocarbonyl)acrylato-kappa(2)O(1):O(3)],
      [Sn(C(4)H(9))(3)(C(14)H(10)NO(3))](n), is composed of polymeric chains wherein
      the metal center exhibits a distorted trigonal-bipyramidal geometry, with three n
      butyl groups defining the trigonal plane [mean Sn[bond]C 2.133 (7) A] and the
      axial positions being occupied by the carboxylate O atoms of two different N-(1
      naphthyl)maleamate ligands with inequivalent Sn[bond]O distances [2.167 (4) and
      2.457 (4) A]. The N-(1-naphthyl)maleamate fragment forms an essentially planar
      seven-membered ring involving an intramolecular N[bond]H...O hydrogen bond.

PMID- 12050415
TI  - catena-Poly[[bis(thiocyanato-kappa N)cadmium(II)]-di-mu-thiourea-kappa(4)S:S].
AB  - The Cd(II) ion in the title complex, [Cd(SCN)(2)[SC(NH(2))(2)](2)](infinity), is
      situated at a centre of symmetry, and is bound to two N atoms belonging to
      thiocyanate groups and to four S atoms of bridging thiourea ligands. The
      structure consists of infinite chains of slightly distorted edge-shared Cd
      centred octahedra. The bridging S atoms of two thiourea ligands comprise the
      common edge. Some thermal properties are described.

PMID- 12050416
TI  - Mixed cobalt(III) complexes with aromatic amino acids and diamines. III. Absolute
      structure of Lambda-trans(O)-(1,2-diaminoethane-kappa(2)N,N)bis(S
      tyrosinato)cobalt(III) chloride tetrahydrate.
AB  - The title compound, [Co(C(9)H(10)NO(3))(2)(C(2)H(8)N(2))]Cl.4H(2)O, is one of six
      possible diastereomers of the (1,2-diaminoethane)bis(S-tyrosinato)cobalt(III)
      complex. The cobalt(III) ion has an octahedral coordination, with three five
      membered chelate rings which have deformed coordination angles and coordinated O
      atoms in trans positions. In comparison with the previously reported crystal
      structure of the Delta-C(1)-cis(O) diastereomer [Miodragovic et al. (2001).
      Enantiomer, 6, 299-308], the compound presented in this paper has more planar
      five-membered aminocarboxylate rings. Complex cations, chloride anions and water
      molecules of crystallization are linked together by a network of hydrogen bonds.
      The chloride anions lie approximately between two Co atoms and form hydrogen
      bonds with all coordinated NH(2) groups. In the crystal structure, there is a
      weak intermolecular pi...pi interaction between the phenyl rings.

PMID- 12050417
TI  - Polymeric bis(N,N-dimethylacetamide)tetrakis(thiocyanato)cadmium(II)mercury(II).
AB  - The title complex, [[CdHg(SCN)(4)(C(4)H(9)NO)(2)](2)](n), contains two
      crystallographically independent Cd(II) centres and two Hg(II) centres. Each
      Cd(II) atom is bound to four N atoms belonging to SCN groups and to two O atoms
      from N,N-dimethylacetamide (DMA) ligands in an octahedral geometry. Each Hg(II)
      centre is tetrahedrally coordinated by four SCN S atoms.

PMID- 12050418
TI  - Hydrogen-bonded supramolecular lattice of the 1:3:4 complex between [5,10,15,20
      meso-tetrakis(4-hydroxyphenyl)porphyrinato-kappa(4)N]zinc(II), dibenzo-24-crown-8
      and methanol.
AB  - The title compound, [5,10,15,20-meso-tetrakis(4-hydroxyphenyl)porphyrinato
      kappa(4)N]zinc(II) tris(dibenzo-24-crown-8) methanol tetrasolvate,
      [Zn(C(44)H(28)N(4)O(4))].3C(24)H(32)O(8).4CH(4)O, was synthesized and its
      molecular structure precisely characterized by low-temperature single-crystal
      analysis. All the components are involved in hydrogen bonding with each other,
      thus forming an extensively hydrogen-bonded supramolecular lattice. The
      functionalized porphyrin moiety coordinates both equatorially and axially to the
      neighboring species.

PMID- 12050419
TI  - Three ruthenocene derivatives: (eta(5)-4,7-dimethylindenyl)(eta(5)
      pentamethylcyclopentadienyl)ruthenium(II), [eta(5)
      [2](4,7)indeno[2]paracyclophanyl](eta(5)
      pentamethylcyclopentadienyl)ruthenium(II) and bis[eta(5)
      [2](4,7)indeno[2]paracyclophanyl]ruthenium(II).
AB  - In the title compounds, [Ru(C(10)H(15))(C(11)H(11))], (III),
      [Ru(C(10)H(15))(C(19)H(17))], (IV), and [Ru(C(19)H(17))(2)], (V), respectively,
      the coordinating ring systems are planar and parallel, with the Ru atoms lying at
      perpendicular distances of Ru-Cp* 1.790 (1) A and Ru-indenyl 1.836 (1) A in
      (III), Ru-Cp* 1.791 (1) A and Ru-indenyl 1.837 (1) A in (IV), and Ru-indenyl
      1.812 (1) A and 1.809 (1) A in (V) (Cp* is pentamethylcyclopentadienyl). The ring
      conformations are eclipsed for (III), staggered for (IV) and intermediate for
      (V). All three compounds show short intermolecular contacts from C-H groups to
      some ring centroids; these could be regarded as C-H.pi hydrogen bonds. The
      molecules of each compound are thus connected via the 2(1) screw axis to form
      layers parallel to the xy plane.

PMID- 12050420
TI  - 6,6-Diphenyl-6,7-dihydro-5H-1,3,4,8-tetrathia-6-stannazulene-2-thione and 6,6'
      spirobi[6,7-dihydro-5H-1,3,4,8-tetrathia-6-stannazulene]-2,2'-dithione.
AB  - The title compounds, [Sn(C(6)H(5))(2)(C(5)H(4)S(5))] and [Sn(C(5)H(4)S(5))(2)],
      respectively, are of interest because they can be regarded as intermediate in
      nature between chelates and heterocyclic compounds containing the C(3)S(5)
      fragment. In contrast with the essentially normal bond lengths and angles within
      the molecules, the molecular conformations are somewhat unexpected, as are the
      intermolecular contacts found in the case of the latter compound.

PMID- 12050422
TI  - Transition metal complexes with thiosemicarbazide-based ligands. XLIII.
      Chlorobis(3-methylisoemicarbazide-kappa(2)N(1),N(4))zinc(II) chloride.
AB  - In the title compound, [ZnCl(C(2)H(7)N(3)S)(2)]Cl, the Zn(II) ion is five
      coordinated in a distorted trigonal-bipyramidal arrangement, with the hydrazine N
      atoms located in the apical positions. The structure is stabilized by
      N[bond]H...Cl hydrogen bonds, which involve both the Cl atoms and all the
      hydrogen donors, except for one of the two thioamide N atoms. A comparison of the
      geometry of thiosemicarbazide and S-methylisothiosemicarbazide complexes with
      Zn(II), Cu(II) and Ni(II) shows the pronounced influence of the hydrogen-bond
      network on the coordination geometry of Zn(II) compounds.

PMID- 12050421
TI  - cis-Dichloro[tris(diphenylphosphinoethyl)amine]ruthenium(II)-chloroform-water
      (1/2.5/1).
AB  - In the title compound, [RuCl(2)(C(42)H(42)NP(3))] x 2.5CHCl(3) x H(2)O, the Ru
      atom is six-coordinated, to one tetradentate tris(diphenylphosphinoethyl)amine
      ligand and two Cl atoms, in a distorted octahedral arrangement. Molecules of
      chloroform and water stabilize the framework through intermolecular hydrogen
      bonds.

PMID- 12050423
TI  - (-)-alpha-Isosparteine copper(II) diazide.
AB  - In the title complex, [Cu(N(3))(2)(C(15)H(26)N(2))], the Cu atom is surrounded by
      the two N atoms of the chelating (-)-alpha-isosparteine ligand and another two N
      atoms from the two azide anions, forming a distorted CuN(4) tetrahedron. The two
      azide anions are terminally bound to the Cu(II) atom, and the dihedral angle
      between the N(sparteine)[bond]Cu[bond]N(sparteine) and
      N(azide)[bond]Cu[bond]N(azide) planes is 50.0 (2) degrees.

PMID- 12050425
TI  - Isomeric pyrazolo[3,4-d]pyrimidine-based molecules: disappearance of dimerization
      due to interchanged substitutions.
AB  - In 5-benzyl-1,7-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine-4,6
      dione, C(14)H(14)N(4)O(2), which crystallizes in space group P 1 macro, weak
      intermolecular C[bond]H...O hydrogen bonds generate dimers. The isomeric compound
      1-benzyl-5,7-dimethyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-d]pyrimidine-4,6-dione,
      C(14)H(14)N(4)O(2), crystallizes in space group P2(1)/n, and shows no such
      dimerization. Instead, it exhibits C[bond]H...pi interactions with the phenyl
      ring. In both structures, the molecules are linked by aromatic pi-pi-stacking
      interactions.

PMID- 12050426
TI  - 5-[N-(1H-Benzotriazol-1-ylmethyl)amino]-3-tert-butyl-1-phenylpyrazole: sheets
      built from N[bond]H...N, C[bond]H...N and C[bond]H...pi(pyrazole) interactions.
AB  - In the title compound, C(20)H(22)N(6), the molecules are linked into a chain of
      rings by N[bond]H...N [H...N 2.16 A, N...N 2.950 (3) A and N[bond]H...N 149
      degrees] and C[bond]H...N [H...N 2.55 A, C...N 3.481 (3) A and C[bond]H...N 165
      degrees ] hydrogen bonds, and these chains are linked into sheets by means of
      C[bond]H...pi(pyrazole) interactions.

PMID- 12050424
TI  - Dichlorobis(pyridine-kappa N)bis(3,3,3-trifluoropropyl-kappa C(1))tin(IV).
AB  - In the title compound, [Sn(C(3)H(4)F(3))(2)Cl(2)(C(5)H(5)N)(2)], the Sn atom lies
      on an inversion centre and is octahedrally coordinated by two Cl atoms, two
      trifluoropropyl groups and two N atoms in an all-trans configuration. The
      electronegative trifluoropropyl groups increase the electrophilic properties of
      the Sn atom, and the Sn[bond]Cl and Sn[bond]N bonds are shortened in comparison
      with those reported for analogous compounds.

PMID- 12050427
TI  - Polymeric methylenebis(diphenylphosphine oxide) hydrogen triiodide.
AB  - The conformation of the cationic part of the title compound,
      [[(C(6)H(5))(2)POH(0.5)](2)CH(2)]I(3) or dppmO(2)H(+) x I(3)(-) (dppm is
      diphenylphosphinomethane), is determined by hydrogen bonds between cations of
      monoprotonated [(C(6)H(5))(2)P([double bond]O)](2)CH(2) (dppmO(2)). Symmetric
      P[double bond]O...H...O[bond]P bridging, with H atoms lying on centres of
      inversion, leads to chain-like polymeric cations, (dppmO(2)H(+))(x), made up of
      H...OP(C(6)H(5))(2)[bond]CH(2)[bond](C(6)H(5))(2)PO... moieties. These are, in
      turn, cross-connected by non-classical C[bond]H...I contacts between the
      (dppmO(2)H(+))(x) methylene-group H atoms and the terminal I atoms of the
      triiodide anions, which display crystallographic inversion symmetry.

PMID- 12050428
TI  - (+-)-12-Oxotricyclo[6.2.2.0(1,6)]dodecane-10-carboxylic acid: hydrogen bonding in
      a tricyclic delta-keto acid.
AB  - The ring system of the title compound, C(13)H(18)O(3), was synthesized by
      addition of ethyl acrylate to the dienamine of 2-octalone. The keto acid
      aggregates in the solid as acid-to-acid dimers [O...O = 2.663 (2) A and
      O[bond]H...O = 170 (3) degrees ] whose centrosymmetric hydrogen bonds lie across
      the a edges and the center of the chosen cell. Three intermolecular C[bond]H...O
      close contacts within 2.7 A were found involving the ketone group.

PMID- 12050429
TI  - The natural diterpenoid kamebanin.
AB  - Kamebanin, alternatively called rel-(-)-(1R,4R,8S,9R,10S,13S,16R)-2,8,16
      trihydroxy-5,5,9-trimethyl-14-methylenetetracyclo[11.2.1.0(1,10).0(4,9)]hexadecan
      15-one, C(20)H(30)O(4), is a natural diterpenoid which has cytotoxic and
      antibacterial activity. The molecule is composed of three six-membered rings,
      which all adopt chair conformations, and one five-membered ring, which adopts an
      envelope conformation. The conjugated alpha-methylenecyclopentanone ring is the
      active part in the molecule due to the ring strain. All three hydroxy groups
      serve as hydrogen-bond donors and acceptors, forming a continuous two-dimensional
      network.

PMID- 12050430
TI  - A dimeric layered structure of a 4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidine
      compound.
AB  - The title compound, 6-methylsulfanyl-1-(3-phenylpropyl)-4,5-dihydro-1H
      pyrazolo[3,4-d]pyrimidin-4-one, C(15)H(16)N(4)OS, crystallizes in space group
      Pbca, with two molecules of similar structure in the asymmetric unit. The
      molecular structure shows the absence of intramolecular stacking in the
      crystalline state, as indicated by earlier (1)H NMR analysis in solution. In
      addition, the crystal packing reveals the formation of a layered structure, due
      mainly to intermolecular N[bond]H...O[double bond]C hydrogen bonding and arene
      arene interactions.

PMID- 12050431
TI  - Methyl 2-O-beta-D-glucopyranosyl-alpha-L-rhamnopyranoside.
AB  - The overall conformation of the title compound, C(13)H(24)O(10), is described by
      the glycosidic torsion angles phi(H) (H1(g)[bond]C1(g)[bond]O2(r)[bond]C2(r)) and
      psi(H) (C1(g)[bond]O2(r)[bond]C2(r)[bond]H2(r)), which have values of 13.6 and
      16.1 degrees, respectively. The former is significantly different from the value
      predicted by consideration of the exo-anomeric effect (phi(H) approximately 60
      degrees ) and from that in solution (phi(H) approximately 50 degrees ), as
      determined previously by NMR spectroscopy. An intramolecular O3(r)[bond]H...O2(g)
      hydrogen bond may help to stabilize the conformation in the solid state. The
      orientation of the hydroxymethyl group of the glucose residue is gauche-gauche,
      with a torsion angle omega (O5(g)[bond]C5(g)[bond]C6(g)[bond]O6(g)) of -70.4 (4)
      degrees. Both pyranose rings are in their expected chair conformations, i.e.
      (4)C(1) for D-glucose and (1)C(4) for L-rhamnose.

PMID- 12050432
TI  - 2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-6-methoxy-3-(3,4,5
      trimethoxybenzoyl)indole.
AB  - In the crystal structure of the title compound, C(32)H(39)NO(7)Si, all geometric
      parameters fall within experimental error of expected values. The analysis of
      molecular-packing plots reveals an infinite two-dimensional linear array running
      parallel to the b axis, formed by one N[bond]H...O intermolecular hydrogen
      bonding interaction. Several potential C[bond]H...O interactions are also
      present.

PMID- 12050433
TI  - (+-)-Tartaric acid.
AB  - (+-)-Tartaric acid, C(4)H(6)O(6), crystallized from ethanol in space group P 1
      macro. The structure is characterized by five hydrogen bonds, including the
      formation of a centrosymmetric carboxylic acid dimer which forms infinite chains
      along the body diagonal. These chains form sheets via hydrogen bonding between
      alpha-hydroxyl groups. The sheets are connected through a bifurcated hydrogen
      bond. Structural comparisons are made with homochiral (2R,3R)-(+)-tartaric acid.

PMID- 12050434
TI  - 2-[3-Furyl(hydroxy)methyl]-2,3-dimethylcyclohexanone.
AB  - Contribution No. 1750 of the Instituto de Quimica, UNAM, Mexico. In the molecule
      of the title compound, C(13)H(18)O(3), there is a syn relationship between the
      two vicinal methyl groups. The six-membered ring adopts a chair conformation,
      with one equatorial and two axial groups, and the furyl group is almost parallel
      to the ketone group. Intermolecular hydrogen bonds [O[bond]H...O[double bond]C
      2.814 (3) A] form chains along [100].

PMID- 12050435
TI  - Melaminium glutarate monohydrate.
AB  - The crystal structure of the title new melaminium salt, 2,4,6-triamino-1,3,5
      triazin-1-ium glutarate monohydrate, C(3)H(7)N(6)(+) x C(5)H(7)O(4)(-) x H(2)O,
      is built up from singly protonated melaminium residues, mono-dissociated
      glutarate ions and water molecules. The melaminium residues are interconnected by
      four N[bond]H...N hydrogen bonds to form chains. These chains of melaminium
      residues form a stacking structure. The glutarate anions form a hydrogen-bonded
      zigzag polymer of the form [...HOOC(CH(2))(3)COO...HOOC(CH(2))(3)COO...](n). The
      oppositely charged moieties, i.e. the melaminium and glutarate chains, form two
      dimensional polymeric sheets. These sheets are interconnected by O[bond]H...O
      hydrogen bonds between the COO(-) moieties and the water molecules, and these
      hydrogen bonds stabilize the stacking structure.

PMID- 12050436
TI  - 1-(1-Benzoylpropen-2-yl)-3-methylisothiosemicarbazide.
AB  - The structure of the title S-alkylated isothiosemicarbazide, C(12)H(15)N(3)OS,
      was determined by single-crystal diffractometry and compared with the structures
      of other compounds containing the S-alkylthiosemicarbazide moiety. Such
      structures cluster into two groups, according to the different orientation of the
      [bond]SR group with respect to the hydrazine N atom of the thiosemicarbazide. The
      cis arrangement is preferred by most molecules in the solid state, in spite of
      the possibility of intramolecular N[bond]H...N interactions in the opposite
      orientation.

PMID- 12050437
TI  - 1,3-Bridged p-methyloctahomotetraoxacalix[4]arene-bis-crown-3.
AB  - The title compound, 13,21,35,43-tetramethyl-3,6,9,17,25,28,31,39,46,49
      decaoxaheptacyclo[21.21.3.3(11,33).0(2,41).0(10,15).0(19,24).0(32,37)]pentaconta
      1,10,12,14,19,21,23,32,34,36,41,43-dodecaene, C(44)H(52)O(10), differs from
      previously reported 1,3-bridged calix[4]arene[bond]bis-crown compounds in having
      an enlarged calixarene ring and shorter polyoxyethylene bridges. The cavity is
      partly filled by the bridges.

PMID- 12050438
TI  - N,N'-Dithiobisphthalimide-1,4-dioxan (1/0.6): a C2/c solvate with disordered
      solvent molecules localized in channels.
AB  - N,N'-Dithiobisphthalimide crystallizes from 1,4-dioxan solution as a solvate,
      3C(16)H(8)N(2)O(4)S(2) x 1.8C(4)H(8)O(2), having space group C2/c. Four of the 12
      C(16)H(8)N(2)O(4)S(2) molecules in the unit cell lie on twofold rotation axes,
      while the other eight lie in general positions. These molecules are linked by
      aromatic pi-pi-stacking interactions and by C[bond]H...O hydrogen bonds to form a
      framework enclosing continuous channels running parallel to the [101] direction,
      which account for ca 20% of the unit-cell volume. The dioxan molecules lie in
      these channels disordered across two sets of sites, with one set across an
      inversion centre and the other across a twofold rotation axis.

PMID- 12050439
TI  - The effect of molecular planarity on crystal non-centrosymmetry in benzylidene
      aniline derivatives.
AB  - In the title compound, N-(2-methoxyphenyl)-4-nitrobenzylideneamine,
      C(14)H(12)N(2)O(3), the two phenyl rings make a dihedral angle of 48.0 (2)
      degrees and the nitro group is at an angle of 6.5 (1) degrees with respect to its
      attached phenyl ring. In the crystal structure, molecules are related as
      centrosymmetric pairs through pi-pi interactions and are further connected
      through strong C[bond]H...O hydrogen bonds [C...O 3.4259 (17) A and C[bond]H...O
      167 degrees ], forming molecular stacks along [100]. These stacks associate
      further through longer C[bond]H...O interactions, forming two-dimensional
      networks. In the c direction, there are only weak van der Waals interactions. The
      relationship between the molecular planarity and its centrosymmetry is also
      briefly described.

PMID- 12050441
TI  - 2-Amino-4,6-bis(benzyloxy)-5-nitrosopyrimidine: chains built from three-centre
      N[bond]H...(N,O) and N[bond]H...pi(arene) hydrogen bonds.
AB  - The molecules of the title compound, C(18)H(16)N(4)O(3), exhibit a very polarized
      molecular-electronic structure. The molecules are linked into chains by a
      combination of an asymmetric three-centre N[bond]H...(N,O) hydrogen bond [H...N
      2.19, H...O 2.54, N...N 3.041 (4) and N...O 2.977 (4) A, and N[bond]H...N 168,
      N[bond]H...O 112 and N...H...O 67 degrees ] and an N[bond]H...pi(arene)
      interaction [H...Cg 2.67 A, N...Cg 3.496 (4) A and N[bond]H...Cg 163 degrees; Cg
      is a benzyl ring centroid].

PMID- 12050440
TI  - O-Benzyl-N-tert-butoxycarbonyl-N-methyl-L-tyrosine.
AB  - The crystal structure of the title compound, alternatively called 3-[4
      (benzyloxy)phenyl]-2-(N-tert-butoxycarbonyl-N-methylamino)propionic acid,
      C(22)H(27)NO(5), has been studied in order to examine the role of N-methylation
      as a determinant of peptide conformation. The conformation of the tert
      butoxycarbonyl group is trans-trans. The side chain has a folded conformation and
      the two phenyl rings are effectively perpendicular to one another. The
      carboxylate hydroxyl group and the urethane carbonyl group form a strong
      intermolecular O[bond]H...O hydrogen bond.

PMID- 12050442
TI  - A [4 pi+4 pi] intramolecular photocyclomer of 9-anthroic anhydride: 5,6,11,12
      tetrahydro-5,12;6,11-di-o-benzenodibenzo[a,e]cyclooctene-5,6-dicarboxylic
      anhydride.
AB  - The title compound, C(30)H(18)O(3), was obtained by light irradiation of a
      dichloroethane solution of 9-anthroyl chloride and 9-anthroic acid. The
      molecules, which possess approximately mm2 local symmetry, are packed in columns,
      the oxygenated moieties facing each other according to the symmetry of a
      monoclinic lattice. The space group of the crystal is P2(1)/c, with a whole
      molecule as the asymmetric unit. The structure is compared with those of similar
      dianthracene derivatives.

PMID- 12050443
TI  - (1R)-2-[(3R,4S)-3-Methyl-4-(N-phenyl-N-propionylamino)piperidin-1-yl]-1
      phenylethyl p-bromobenzoate and N-[(3R,4S)-1-[(2S)-2-(4-bromophenyl)-2
      hydroxyethyl]-3-methyl-piperidin-4-yl]-N-phenylacrylamide.
AB  - Both title compounds, C(30)H(33)BrN(2)O(3) and C(23)H(27)BrN(2)O(2),
      respectively, are brominated derivatives of the potent opioid cis-beta-hydroxy-3
      methylfentanyl (ohmefentanyl). Ohmefentanyl has three asymmetric C atoms and,
      therefore, has eight possible stereoisomers. The absolute configurations of the
      title compounds were determined to assign the proper configuration of two of
      these stereoisomers and the compounds have the same stereochemistry at two of the
      three asymmetric C atoms.

PMID- 12050444
TI  - 1-Methyl-1H-imidazo[4,5-f]quinolin-6-ium chloride monohydrate.
AB  - The title compound, C(11)H(10)N(3)(+) x Cl(-) x H(2)O, belongs to the N1-methyl
      substituted imidazo[4,5-f]quinoline family, in which the heterocyclic ring is
      protonated at the pyridine rather than at the imidazole N atom. The molecule as a
      whole is almost exactly planar. The molecular structure has been compared with
      that of the 2-amino analogue described in the literature, and it was found that
      the extra amino group of the latter is involved in conjugation with the adjacent
      double bond, i.e. the conjugation does not extend over the entire heterocyclic
      system. The cation of the title compound forms a strong hydrogen bond with the
      Cl(-) anion and the anions are interconnected by the water solvent molecule.

PMID- 12050445
TI  - Precursor of a beta-lactamase inhibitor: allyl (4S,8S,9R)-10-[(E)-ethylidene]-4
      methoxy-11-oxo-1-azatricyclo[7.2.0.0(3,8)]undec-2-ene-2-carboxylate.
AB  - The molecular structure of the title tricyclic compound, C(17)H(21)NO(4), which
      is the immediate precursor of a potent synthetic inhibitor [Lek157: sodium
      (8S,9R)-10-[(E)-ethylidene]-4-methoxy-11-oxo-1-azatricyclo[7.2.0.0(3,8)]undec-2
      ene-2-carboxylate] with remarkable potency, provides experimental evidence for
      the previously modelled relative position of the fused cyclohexyl ring and the
      carbonyl group of the beta-lactam ring, which takes part in the formation of the
      initial tetrahedral acyl-enzyme complex. In this hydrophobic molecule, the
      overall geometry is influenced by C[bond]H...O intramolecular hydrogen bonds
      [3.046 (4) and 3.538 (6) A, with corresponding normalized H.O distances of 2.30
      and 2.46 A], whereas the molecules are interconnected through intermolecular
      C[bond]H...O hydrogen bonds [3.335 (4)-3.575 (5) A].

PMID- 12050446
TI  - A neutral complex of an azino[bond]DTDAF compound with TCNQ.
AB  - In the crystal structure of the title 1:1 complex, ethyl 2-[[5-(ethoxycarbonyl)
      2,3-dihydro-3,4-dimethyl-1,3-thiazol-2-ylidene]hydrazono]-2,3-dihydro-3,4
      dimethyl-1,3-thiazole-5-carboxylate-7,7,8,8-tetracyano-p-quinodimethane (1/1),
      C(16)H(22)N(4)O(4)S(2) x C(12)H(4)N(4), the planar donor and tetracyano-p
      quinodimethane (TCNQ) molecules are each located on inversion centres and are
      stacked alternately. The bond lengths indicate that, in this complex, the donor
      and acceptor are neutral, as confirmed by IR investigation.

PMID- 12050447
TI  - "I" is for image.

PMID- 12050448
TI  - Squeaky wheel versus hospital leaders.

PMID- 12050449
TI  - Get a grip on billing and reimbursement.
AB  - Managing Medicare outpatient reimbursement has ballooned into a complex, full
      time job. Here's an overview of upcoming initiatives that require changes to your
      financial procedures.

PMID- 12050450
TI  - Up-front leaders guide staff to the future.
AB  - Successful leaders employ a forthright management style to move staff forward.

PMID- 12050451
TI  - Remember reverence.

PMID- 12050455
TI  - Spell out LIP requirements.
AB  - Review practice guidelines for three licensed independent practitioners-
      certified nurse anesthetists, nurse practitioners, and nurse midwives.

PMID- 12050456
TI  - DNR orders: proceed with caution.
AB  - To avoid liability and best meet patients' requests, caregivers must fully
      understand the process that validates DNR directives.

PMID- 12050457
TI  - Tap into a new workforce.

PMID- 12050459
TI  - Not-so-mandatory overtime.

PMID- 12050460
TI  - Pain management: the global connection.
AB  - Understanding pain and the cultural perceptions patients and staff hold about it
      is crucial to developing a pain management program that complies with Joint
      Commission requirements.

PMID- 12050461
TI  - Avoid PCU bottlenecks with proper admission and discharge criteria.
AB  - As hospitals strive to control costs and free up more critical care beds,
      progressive care nurse managers need to set appropriate admission and discharge
      guidelines.

PMID- 12050462
TI  - The safety needle switchover, part 2 of 2.
AB  - South Carolina's Greenville Hospital System (GHS) minimizes caregivers' exposure
      to blood and body fluid through a risk-reduction program that hinges on feedback
      from data analysis and frontline staff.

PMID- 12050463
TI  - Spirit lifting.
AB  - Follow the example of Southern California's Loma Linda University Medical Center,
      which implemented measures to decrease stress and increase job satisfaction among
      nursing staff.

PMID- 12050464
TI  - Safe and sound.
AB  - Telephone triage requires careful staff selection, support, and service
      supervision.

PMID- 12050465
TI  - Come health or high water.
AB  - Created by necessity when its Houston, Tex., ED flooded, St. Joseph Hospital's
      new patient care delivery system decreases turnaround time, promoting a more
      patient-focused environment.

PMID- 12050467
TI  - Tap Internet employment resources.

PMID- 12050466
TI  - Revisit patient safety initiatives.
AB  - Updated CMS and JCAHO patient safety recommendations cause health care facilities
      to question their existing policies and procedures.

PMID- 12050468
TI  - The hypothetical way.

PMID- 12050469
TI  - The perception of emotional chimeric faces in schizophrenia: further evidence of
      right hemisphere dysfunction.
AB  - OBJECTIVE: To examine lateral perceptual bias, an index of right hemisphere
      function, and its relation to performance on a standard facial perception test
      and to clinical variables in a large sample of first episode and chronic
      schizophrenia. BACKGROUND: Judgments made on chimeric faces reliably elicit a
      perceptual bias to the left hemispace, presumed to be a result of right
      hemisphere dominance for spatial attention. Recent studies have suggested that
      this bias is reduced or absent in people with schizophrenia. METHODS: Fifty first
      episode and 50 patients with chronic schizophrenic and 50 control subjects were
      given a brief neuropsychologic battery that included a Happy-Sad Chimeric Face
      test and the Benton Facial Recognition Test. All patients were rated on the
      Positive and Negative Syndrome Scale of Schizophrenia after 4 weeks of
      neuroleptic treatment. All were right handed RESULTS: The patients with
      schizophrenia showed a significantly weaker perceptual left hemispatial bias
      compared with controls. In fact the mean bias was in the opposite direction in
      the chronic group. There was no correlation between left hemispatial bias and
      either positive or negative symptoms, current medication dose, or mood. Results
      from the Benton test revealed a performance deficit among the patients with
      schizophrenia compared with controls but was not correlated with performance on
      the chimeric faces test in the patients. CONCLUSIONS: The results confirm a
      specific deficit in right hemisphere attentional functions in schizophrenia,
      which is separate from a general impairment in facial processing. The deficit is
      most marked in chronic patients but further study is required to determine
      whether this is a consequence of prolonged illness.

PMID- 12050470
TI  - Cognitive and behavioral features discriminate between Alzheimer's and
      Parkinson's disease.
AB  - OBJECTIVE: To compare the cognitive and behavioral profiles of Alzheimer's
      disease (AD) and cognitively impaired patients with Parkinson's disease (PD) and
      to determine the individual measures that best discriminate the two patient
      groups. BACKGROUND: Neuropsychologic studies of patients with AD and PD have
      generated debate over the distinction between "cortical" and "subcortical"
      dementias, with some studies showing significant differences and others showing
      little difference in the cognitive profiles of these groups. Studies evaluating
      behavioral differences between the patient groups have been somewhat more
      successful in adequately discriminating these syndromes. To address this issue,
      we examined cognitive and behavioral profiles of patients with AD and cognitively
      impaired patients with PD on two frequently used assessment instruments. METHOD:
      Patients were diagnosed according to published and accepted criteria for AD and
      PD. Eighteen patients with AD and 18 patients with PD, matched on age and
      education, were administered the Mattis Dementia Rating Scale and Frontal Systems
      Behavior Scale (formally Frontal Lobe Personality Scale). RESULTS: The two groups
      did not differ on overall Dementia Rating Scale score or total Frontal Systems
      Behavior Scale score. However, examination of subscale scores revealed that the
      patients with AD performed significantly worse than the patients with PD on the
      Memory subscale of the Dementia Rating Scale, and patients with PD were rated as
      being more apathetic than the patients with AD on the Frontal Systems Behavior
      Scale. When these two variables were entered into a discriminant function
      analysis, an overall classification accuracy of 86% was demonstrated, with 89% of
      the AD group and 83% of the PD group correctly classified. CONCLUSIONS: These
      findings suggest that even though global cognitive dysfunction and behavioral
      disturbance may appear similar in patients with AD and cognitively impaired
      patients with PD, specific measures of these functions that are sensitive to the
      underlying neuropathology of each disease do differ significantly.

PMID- 12050471
TI  - Neurocognitive correlates of response to treatment in formal thought disorder in
      patients with first-episode schizophrenia.
AB  - OBJECTIVE: To examine the independent contribution of executive versus semantic
      function to improvement in formal thought disorder after initial stabilization in
      a first-episode sample. BACKGROUND: Neurocognitive deficits have been suggested
      to predict treatment response in patients with first-episode schizophrenia.
      However, studies targeting putative neurocognitive mechanisms to explore
      improvement in positive psychotic symptoms and especially formal thought disorder
      are lacking. METHOD: Formal thought disorder symptoms in 81 first-episode
      patients with schizophrenia or schizoaffective disorder either showed significant
      improvement (responders > 60% change) or not (nonresponders < 60%) 6 months after
      initial stabilization of symptoms. These two groups were compared on
      neuropsychologic (n = 16), clinical (n = 15), and volumetric measures of the
      frontal and temporal lobes (n = 5) in univariate analyses. The variables that
      significantly differed between these two groups were used in a forward binary
      logistic regression analysis. RESULTS: As compared with nonresponders, responders
      were younger at time of testing, had higher verbal intelligence and reading
      achievement scores, higher scores on the arithmetic subtest of the Wechsler Adult
      Intelligence Scale-Revised, and lower number of perseverative responses on the
      Wisconsin Card Sort Test. Responders also had larger frontal lobe volumes than
      nonresponders. Only two measures (perseverative responses on the Wisconsin Card
      Sort Test and age at testing) entered the regression equation. Measures of
      semantic competency and volumetric measures of the temporal lobes were not
      associated with formal thought disorder improvement. CONCLUSIONS: Neurocognitive
      deficits are associated with treatment response in formal thought disorder in
      first-episode patients with schizophrenia. The improvement in formal thought
      disorder is more strongly linked to executive than semantic function in this
      sample, pointing to the salience of frontal systems in treatment response in
      positive psychotic symptoms.

PMID- 12050473
TI  - Dissociation between spontaneous and reactive flexibility in early Parkinson's
      disease.
AB  - OBJECTIVE: This study was designed to examine the relations between the severity
      of motor symptoms and impaired cognitive flexibility in Parkinson's disease.
      BACKGROUND: Studies that examine cognitive flexibility in Parkinson's disease
      report conflicting results. We hypothesized that such inconsistency may reflect a
      differential pattern of impairment on tasks that measure spontaneous versus
      reactive flexibility. METHODS: The performance of tasks requiring either
      spontaneous (Alternate Uses) or reactive (Wisconsin Card Sorting Test) cognitive
      flexibility was examined in newly diagnosed unmedicated patients with idiopathic
      Parkinson's disease, as compared with age- and education-matched controls. The
      correlation between the degree of deficit and severity of motor symptoms was also
      examined. RESULTS: Patients were significantly worse than controls in performing
      both types of tasks. The patients' performance on tasks of spontaneous reactivity
      was not correlated with the presence or severity of the motor signs and symptoms.
      However, only patients showing signs of bradykinesia were impaired on a measure
      of reactive cognitive flexibility and the degree of impairment was significantly
      correlated with the severity of bradykinesia. CONCLUSIONS: These findings suggest
      that the dissociation between the two types of cognitive flexibility may reflect
      the differential involvement of the mesocortical and striatonigral dopaminergic
      circuits in the mediation of these tasks.

PMID- 12050472
TI  - The prevalence and correlates of neuropsychiatric symptoms in a population with
      Parkinson's disease in Mexico.
AB  - OBJECTIVE: To study the incidence of behavioral abnormalities in patients with
      Parkinson's disease (PD) and extend them to a Mexican population. BACKGROUND:
      Reports from the US and Europe suggest depression, anxiety, and apathy occur with
      increased frequency in PD, but data on the occurrence of neuropsychiatric
      symptoms in patients with PD in Latin America are lacking. METHODS: The
      investigators performed a cross-sectional survey of psychiatric symptoms and
      cognitive status in 40 patients with PD and 83 controls in Mexico City. RESULTS:
      Results were compared between groups and correlations sought between symptoms and
      disease variables. Patients with PD had a higher rate of dysphoria, anxiety, and
      apathy (p < 0.001). Within the patients with PD, there was a positive correlation
      between disease severity (rho = 0.496), age (rho = 0.340), and degree of self
      rated depression. CONCLUSIONS: This study confirmed the observation previously
      described in other PD populations of increased rates of dysphoria, anxiety, and
      apathy in Mexican patients with PD. We found no relation between disease
      duration, severity, cognitive impairment, and neuropsychiatric symptoms as
      measured on the Neuropsychiatric Inventory, possibly a result of the relative
      lack of advanced cases in our population.

PMID- 12050474
TI  - Influence of cognitive reserve on neuropsychologic functioning in Alzheimer's
      disease type sporadic in subjects of Spanish nationality.
AB  - OBJECTIVE: To evaluate the influence of cognitive reserve or brain reserve
      capacity on neuropsychologic performance in Spanish patients with Sporadic Late
      Onset Alzheimer Disease. BACKGROUND: The three authors of this paper are
      professors who teach in psychology departments in different Spanish universities
      of recognized prestige. METHODS: The sample used in this study comprised 97
      subjects divided into two groups: one of 51 subjects diagnosed with Sporadic Late
      Onset Alzheimer Disease and another of 46 subjects who, with no family history of
      dementia at the time of examination, showed no type of neurologic or psychiatric
      disorder, nor did they have any record of alcoholism or drug-addiction. The
      evaluation of each subject in the clinical group consisted of a full neurologic
      examination, a neuropsychologic evaluation with a battery of tests designed for
      this study, and an assessment of mood with the Beck Depression Inventory.
      Cognitive reserve scores were based on a combination of years of education, a
      measure of occupational attainment, and an estimate of premorbid intelligence.
      Empirically derived factor scores and clinical summary ratings summarized
      performance on a battery of neuropsychologic tests. RESULTS: The subjects with
      Alzheimer's disease with low cognitive reserve scores exhibited significantly
      greater deficits in measures of memory, attention language, executive
      functioning, and visuospatial performance than did the subjects with Alzheimer's
      disease with high cognitive reserve. Early neuropsychologic impairments in
      Alzheimer's disease are most evident in individuals with lower cognitive reserve.
      CONCLUSIONS: Our results reveal that patients diagnosed with Alzheimer's disease
      who have a high cognitive reserve attain a higher neuropsychologic performance
      than those with a low reserve. These results support the theory on the important
      protective role of education as well as that of certain occupational aspects
      (such as mental and cognitive demands from one's usual work) in the incidence of
      cognitive deterioration and dementia. These factors would increase cognitive
      reserve by requiring greater and more efficient communicative capacity from
      subjects as would participation in complex tasks that require the setting in
      motion of cognitive resources and capabilities.

PMID- 12050475
TI  - The role of injury severity in neurobehavioral outcome 3 months after traumatic
      brain injury.
AB  - OBJECTIVE/BACKGROUND: To assess neurobehavioral outcome using the Neurobehavioral
      Rating Scale-Revised (NRS-R), an instrument with established specificity and
      validity in Traumatic Brain Injury (TBI) in a sample including the full spectrum
      of TBI severity 3 months after injury. METHOD: A cohort group of 102 subjects
      with mild TBI, 41 with moderate TBI, and 139 with severe TBI, from multiple
      academic trauma centers, were assessed using the NRS-R and the Glasgow Outcome
      Scale. RESULTS: Principal components analysis of the NRS-R resulted in a 3-factor
      model: (1) Cognitive, (2) Emotional, and (3) Hyperarousal. At 3 months, subjects
      with severe TBI show greater difficulties in cognitive and hyperarousal, but not
      emotional domains, than those with mild to moderate TBI. More than one third of
      subjects in all injury severity groups showed evidence of anxiety, depression,
      irritability, mental fatigability, and memory dysfunction. Scores on the NRS-R
      were related to outcome on the Glasgow Outcome Scale. CONCLUSIONS: Three months
      after injury, subjects with severe TBI have more dysfunction in cognitive and
      behavioral (but not emotional) domains than those with mild-to-moderate TBI. The
      NRS-R is a useful tool for assessing the full spectrum of neurobehavioral
      dysfunction at all ranges of TBI severity.

PMID- 12050476
TI  - Grip-strength, fatigue, and motor perseveration in anxious men without
      depression.
AB  - OBJECTIVE: To investigate the influence of anxiety without depression on
      functional motor asymmetry in adult men. Thus, left-and right-hand grip strength,
      fatigue across trials, and motor perseveration was examined among 60 right-handed
      men, half of whom had been classified as anxious without depression (HI, n = 30)
      and the other half as nonanxious without depression (LO, n = 30). BACKGROUND:
      There is substantial empirical support for the notion that individuals with
      negative affect experience relative right anterior activity. Moreover, previous
      studies using other groups of interest (e.g., depression and hostility) have
      found evidence of functional motor asymmetry that is supportive of relative right
      anterior activation during negative affect. Less is known about functional motor
      asymmetry among individuals that report anxiety without depression. METHOD: To
      obtain indices of perseveration, strength, and fatigue, HI and LO anxious
      subjects were asked to successively squeeze a hand dynamometer. Dependent
      measures (in kg) were derived from performance with the left and right hands
      across trials. RESULTS: In contrast to LO anxious subjects, HI anxious subjects
      did not demonstrate right-hand superiority for grip-strength. Moreover,
      significant positive correlations existed between grip strength and trait anxiety
      scores for LO anxious subjects, but not for HI anxious subjects. CONCLUSIONS: The
      data are partially supportive of differences in functional motor asymmetry
      between HI and LO anxious individuals. The findings are interpreted as supportive
      of relative right anterior activity (and possibly decreased left anterior
      activity) among individuals that report elevated levels of anxiety. Implications
      for relative right-hemisphere activity and decreased left anterior activity are
      discussed, and alternative explanations are introduced.

PMID- 12050477
TI  - A shrinking span of temporal continuity in dementia of the Alzheimer's type.
AB  - OBJECTIVE: To examine the integrity of memory function in terms of temporal
      continuity in a way that would engage a patient in everyday behavior, such as
      informal conversation, but still allow memory function to be quantified.
      BACKGROUND: This bedside task allowed the measurement of the duration of
      continuous, conscious experience of the present and was therefore termed "span of
      temporal continuity." METHOD: We tracked span of temporal continuity in a patient
      we believed was in the very early stages of Alzheimer's disease longitudinally.
      RESULTS: We found a progressively smaller span in which this patient experiences
      continuity in keeping with disease duration. CONCLUSION: In terms of span of
      temporal continuity in our single subject, we were able to document a
      progressively smaller span in which VB experiences continuity before any telling
      neuropsychologic deficits. Hence, our measure might serve to better identify and
      characterize dementia of the Alzheimer's type in its incipient stages.

PMID- 12050478
TI  - Mechanisms of dressing apraxia: a case study.
AB  - OBJECTIVE: To investigate the neural mechanisms that differentiate dressing
      apraxia from other forms of apraxia such as ideomotor apraxia. Hypotheses
      examined included (1) that dressing is more sensitive to alternations in body
      schema, (2) that dressing is a demanding bimanual task, and (3) that clothing
      represents a particularly complex spatial problem. BACKGROUND: A focal
      degenerative condition can specifically target a function such as dressing,
      allowing a unique approach to its study. METHOD: A case study of the cognitive
      impairments of a 75-year-old man who presented with progressive dressing
      difficulties in the absence of neglect or motor disturbances. RESULTS:
      Neuropsychologic testing indicated possible executive function deficits as well
      as visuospatial and visuocontructional deficits, but intact praxic skills, verbal
      abilities, and visual recognition skills. In addition, testing revealed no
      evidence of Balint's or impairments in body schema. CONCLUSION: Overall, the test
      results suggested that visuospatial dysfunction is the underlying deficit in
      dressing apraxia. The present case study confirmed the independence of praxic
      functioning from spatial ability and conversely, the dependence of dressing on
      spatial ability.

PMID- 12050480
TI  - The endourological management of complications associated with horseshoe kidney.
AB  - PURPOSE: Horseshoe kidneys are the most common renal fusion anomalies.
      Ureteropelvic junction obstruction, urolithiasis and renal malignancies are the
      most common complications that occur in this patient population. Endourological
      management of these complications has decreased perioperative morbidity. We
      identified the applications of minimally invasive surgery for treating
      complications secondary to horseshoe kidney. MATERIALS AND METHODS: A
      comprehensive literature review of the different endourological approaches in the
      management of complications secondary to horseshoe kidney was performed using
      MEDLINE. RESULTS: Ureteropelvic junction obstruction can be managed by
      percutaneous endopyelotomy or laparoscopic pyeloplasty with good results. Small
      stones associated with horseshoe kidney are best managed by shock wave
      lithotripsy, while stones that have failed management by shock wave lithotripsy
      or are greater than 2 cm. are best managed percutaneously. All patients should
      undergo metabolic evaluation. Ureteroscopy or shock wave lithotripsy is
      associated with a higher residual stone rate than the percutaneous approach.
      Laparoscopic nephrectomy is a safe and feasible option for benign and malignant
      horseshoe kidney diseases. CONCLUSIONS: Endourological techniques can be safe and
      effective for treating complications secondary to horseshoe kidney.

PMID- 12050481
TI  - Studies on prostatic cancer: I. The effect of castration, of estrogen and of
      androgen injection on serum phosphatases in metastatic carcinoma of the prostate.
      1941.

PMID- 12050482
TI  - Laparoscopic radical cystectomy and continent orthotopic ileal neobladder
      performed completely intracorporeally: the initial experience.
AB  - PURPOSE: We introduce the operative technique of laparoscopic radical cystectomy
      and orthotopic ileal neobladder with a Studer limb performed completely
      intracorporeally. MATERIALS AND METHODS: The procedure was performed in 1 man and
      1 woman. Using a 6 port transperitoneal approach, radical cystectomy in the
      female patient and radical cystoprostatectomy in the male patient were completed
      laparoscopically with the urethral sphincter preserved. Bilateral pelvic
      lymphadenectomy was done. A 65 cm. segment of ileum 15 cm. from the ileocecal
      junction was isolated, and ileo-ileal continuity was restored using Endo-GIA
      staplers (U.S. Surgical, Norwalk, Connecticut). The distal 45 cm. of the isolated
      ileal segment were detubularized, maintaining the proximal 10 cm. segment intact
      as an isoperistaltic Studer limb. A globular shaped ileal neobladder was
      constructed and anastomosed to the urethra. Bilateral stented ureteroileal
      anastomoses were individually performed to the Studer limb. All suturing was done
      exclusively using free-hand laparoscopic techniques and the entire procedure was
      completed intracorporeally. An additional case is described of Indiana pouch
      continent diversion in which the pouch was constructed extracorporeally. RESULTS:
      Total operative time for laparoscopic radical cystectomy and orthotopic
      neobladder was 8.5 and 10.5 hours, respectively, with a blood loss ranging from
      200 to 400 cc. Hospital stay was 5 to 12 days and surgical margins of the bladder
      specimen were negative in each case. Both patients with orthotopic neobladder had
      complete daytime continence. Postoperative renal function was normal and
      excretory urography revealed unobstructed upper tracts. During followup ranging
      from 5 to 19 months 1 patient died of metastatic disease, while the other 2 are
      doing well without local or systematic progression. CONCLUSIONS: Laproscopic
      radical cystectomy and orthotopic ileal neobladder performed completely
      intracorporeally are feasible.

PMID- 12050483
TI  - Expression of matrix metalloproteinase in the fluids of renal cystic lesions.
AB  - PURPOSE: Cystic lesions of the kidney are common conditions usually diagnosed by
      imaging. Although simple cysts are easy to diagnose, preoperative diagnosis of a
      complicated cystic lesion can be difficult. There is little information available
      on the biological activity of cystic fluid and associations with
      clinicopathological findings. We analyzed the expression of matrix
      metalloproteinase (MMP) in the fluids of benign and malignant renal cystic
      lesions to clarify matriolytic activities in the cyst. MATERIALS AND METHODS:
      Included in this study were 22 samples of cystic fluids from renal cystic
      lesions, including 14 benign cysts and 8 cystic renal cell carcinomas. MMP-2 and
      9 was determined in fluids using gelatin zymography and enzyme-linked
      immunosorbent assay. RESULTS: MMP-2 expression was ubiquitously observed on
      zymography except for 2 benign cysts associated with acquired cystic disease of
      the kidney. MMP-9 was detected in 7 of 8 carcinomas but in only 2 of 14 benign
      cysts (p <0.01). The concentration of MMP-2 and 9 was significantly higher in
      cystic carcinomas than in benign cysts (p <0.01). CONCLUSIONS: Our data show that
      MMPs were detectable in cystic fluids in the presence of renal cystic changes.
      MMP-2 and 9 are more abundant in cystic carcinoma fluids than in benign cystic
      fluids. These observations suggest that matriolytic enzymes in renal cystic fluid
      reflect biological aggressiveness and in part explain the pathogenesis of renal
      cystic lesions.

PMID- 12050484
TI  - Complications of transperitoneal laparoscopic surgery in urology: review of 1,311
      procedures at a single center.
AB  - PURPOSE: The development of laparoscopic surgery in urology is increasing
      rapidly. We describe our experience with complications during and after
      transperitoneal laparoscopic surgery after 9 years of practice. MATERIALS AND
      METHODS: A total of 1,311 laparoscopic procedures were performed by 5 senior
      urologists in the same department since 1992, of which 72% were classified as
      difficult or very difficult (prostatectomy, nephrectomy for cancer,
      nephroureterectomy, partial nephrectomy, cystectomy, para-aortic lymph node
      dissection), 27.5% as moderately difficult (nephrectomy for benign disease,
      adrenalectomy, genitourinary prolapse, ureteropelvic junction, pelvic and
      ureteral stones, ureterovesical reimplantation, pelvic lymph node dissection) and
      0.5% as easy (lymphocele, renal cyst and so forth). RESULTS: There was no
      mortality or anesthetic complications. The overall transfusion rate was 2.4%.
      Complications were serious in 0.7% of cases, all of which required reoperation,
      intermediate in 1.8% of which 1% required reoperation and minor in 1.1%. The main
      complications were bowel (1.2%), vascular (0.5%) and ureteral injuries (0.8%).
      The conversion rate was 1.2% and the reoperation rate was 2.4%. Of the patients
      1.2% had to be admitted to the intensive care unit. Postoperative complications
      were observed in 19% of cases. Laparoscopic surgery is associated with
      essentially the same complications as open surgery, and they, particularly bowel
      injuries and bleeding, can be diagnosed and often treated with repeat
      laparoscopy. CONCLUSIONS: Complications during and after transperitoneal
      laparoscopy remain low and are not superior to those observed during and after
      open surgery. As laparoscopy becomes more widely used, urologists wishing to
      learn this technique must realize that the learning process is long but
      essential.

PMID- 12050485
TI  - The impact of cystinuria on renal function.
AB  - PURPOSE: Patients with cystinuria frequently have recurrent renal calculi and may
      subsequently require multiple stone removing procedures during their lifetime
      which could have an impact on overall renal function. We determined the potential
      impact of cystinuria and cystine stone formation on the level of renal function
      compared to calcium oxalate stone formers. MATERIALS AND METHODS: Clinical data
      on 40 cystinuric patients followed at 2 medical centers and 45 such individuals
      in a large stone population data base were analyzed. These results were compared
      to data on 3,964 calcium oxalate stone formers enrolled in this data base.
      RESULTS: Mean serum creatinine plus or minus standard deviation for stone forming
      cystinuric patients was significantly higher than that of the calcium oxalate
      cohort (1.13 +/- 0.28 versus 1.01 +/- 0.28 mg./100 ml., p = 0.0001). A
      significantly greater percentage of cystinuric patients (5.8%) had an abnormally
      increased serum creatinine compared to the calcium oxalate stone formers (2.2%, p
      = 0.046). Male gender, increasing number of open surgical stone removing
      procedures and nephrectomy were significant variables associated with an
      increased serum creatinine (p = 0.0010, p = 0.0038, p = 0.0133, respectively). An
      increasing number of open surgical stone removing procedures had a significant
      positive correlation with performance of nephrectomy in the cystinuric population
      (p = 0.0166). A significantly greater percentage of cystinuric patients compared
      to the calcium oxalate cohort were subjected to nephrectomy (14.1% versus 2.9%, p
      = 0.007). CONCLUSIONS: Cystinuric patients have higher serum creatinine levels
      than calcium oxalate stone formers and they are at more risk for renal loss. When
      stone removal is required, a minimally invasive approach is preferred.

PMID- 12050486
TI  - Prevention of spinal bone loss by potassium citrate in cases of calcium
      urolithiasis.
AB  - PURPOSE: We determine if potassium citrate treatment stabilizes spinal bone
      density among patients with recurrent calcium oxalate nephrolithiasis. MATERIALS
      AND METHODS: We studied a group of 16 men and 5 women with stones taking
      potassium citrate from 11 to 120 months. They represented all patients from the
      Stone Clinic who took potassium citrate alone for at least 11 months. L2-L4 bone
      mineral density data before and after potassium citrate treatment were retrieved
      retrospectively and analyzed. RESULTS: In the combined group L2-L4 bone mineral
      density increased significantly by 3.1% over mean duration of 44 months. Z score,
      corrected for age matched normal values, increased significantly by 3.8%. Urinary
      pH, citrate and potassium increased significantly during treatment but urinary
      calcium did not change. CONCLUSIONS: Potassium citrate, a commonly used drug for
      the prevention of recurrent nephrolithiasis, may avert age dependent bone loss.
      Spinal bone density increased in most patients when it normally decreases.

PMID- 12050487
TI  - Comparison of intravenous sedation versus general anesthesia on the efficacy of
      the Doli 50 lithotriptor.
AB  - PURPOSE: We compared the impact of intravenous sedation versus general anesthesia
      on the efficacy of extracorporeal shock wave lithotripsy. MATERIALS AND METHODS:
      From November 1997 to May 1998, 295 patients with a single renal or upper
      ureteral radioopaque stone of less than 2 cm. were treated with the Doli 50
      lithotriptor (Dornier Medical Systems, Marietta, Georgia). The treating
      anesthesiologist and patient together elected intravenous sedation or general
      anesthesia. Of the 92 patients 60 (65%) treated under intravenous sedation and
      126 of the 203 (62%) treated under general anesthesia had 3-month followup
      records available for review. Extracorporeal shockwave lithotripsy was considered
      a failure if residual stone fragments remained after 3 months, or an auxiliary
      procedure or re-treatment was required. RESULTS: At 3 months the stone-free rate
      in patients treated under intravenous sedation was 55% compared with 87% in those
      treated under general anesthesia (p <0.001). There was no statistically
      significant difference in treatment time or the power index in the 2 groups.
      Stone size (1 to 10 versus 11 to 20 mm.) did not significantly affect the
      anesthesia specific stone-free rate. CONCLUSIONS: For single renal or upper
      ureteral stones less than 2 cm. a significantly better 3-month stone-free rate is
      achieved with the Doli 50 lithotriptor when general anesthesia is used instead of
      intravenous sedation.

PMID- 12050488
TI  - Effects of extracorporeal shock wave lithotripsy on plasma levels of nitric oxide
      and cyclic nucleotides in human subjects.
AB  - PURPOSE: The role of extracorporeal shock wave lithotripsy (ESWL, Dornier
      Medizintechnik GmbH, Wessling Munchen, Germany) on plasma nitric oxide (NO) and
      cyclic nucleotides was investigated. It is known that ESWL increased plasma
      levels of vasoactive substances. MATERIALS AND METHODS: A total of 28 patients
      undergoing ESWL for renal (14) and lower ureteral (14) stones participated in a
      prospective study. Peripheral blood samples were analyzed for plasma nitrite, NO
      metabolite, cyclic 3', 5'-guanosine monophosphate (cGMP), cyclic 3',5'-adenosine
      monophosphate and plasma renin activity before, immediately after, 30 and 60
      minutes after ESWL. Urine samples were also analyzed for nitrite before,
      immediately after, 30 and 60 minutes after ESWL. Blood pressure and pulse rate
      were measured before and after ESWL. RESULTS: ESWL increased mean plasma nitrite
      levels. Before, immediately after, 30 and 60 minutes after ESWL mean plasma
      nitrate plus or minus standard error in patients with renal versus lower ureteral
      stones was 43.6 +/- 8.5, 52.8 +/- 7.4, 54.0 +/- 8.0 and 52.2 +/- 9.1 versus 27 +/
      5.8, 24.6 +/- 4.7, 23.6 +/- 4.8 and 28.0 +/- 7.1 nM., respectively. Before,
      immediately after, 30 and 60 minutes after ESWL mean plasma cGMP in patients with
      renal versus lower ureteral stones was 1.21 +/- 0.1, 1.64 +/- 0.16, 1.52 +/- 0.12
      and 1.58 +/- 0.14 versus 1.45 +/- 0.18, 1.52 +/- 0.13, 1.52 +/- 0.15 and 1.51 +/-
      0.11 fmol., respectively. Cyclic 3',5'-adenosine monophosphate was not increased
      by ESWL in patients with renal stones. Urine nitrite increased slightly but not
      significantly after ESWL. Plasma cyclic nucleotides and nitrite, and urine
      nitrite were not changed by ESWL in patients with lower ureteral stones. Plasma
      renin activity decreased significantly in patients with renal stones 60 minutes
      after ESWL. Blood pressure and pulse rates increased mildly without statistical
      significance after ESWL for renal stones. CONCLUSIONS: ESWL increases plasma
      nitrite and cGMP in patients with renal stones, suggesting that shock waves
      stimulate the NO-cGMP signaling pathway.

PMID- 12050489
TI  - Ureteroscopic treatment of lower pole calculi: comparison of lithotripsy in situ
      and after displacement.
AB  - PURPOSE: Ureteroscopic management is a viable option for lower pole calculi less
      than 2 cm. Recently a technique was described to displace the calculus into a
      more accessible calix using a nitinol basket or grasper before lithotripsy. We
      compared the efficacy and safety of this technique with in situ treatment of
      small and intermediate lower pole calculi. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 95 ureteroscopy cases performed at our
      institution from January 1997 through August 2001 for renal calculi located only
      in the lower pole. Preoperative patient characteristics, stone size, operative
      details, complications and outcomes were compared for calculi treated in situ and
      those displaced before treatment. RESULTS: Adequate followup was available on 78
      patients. Patients in the displacement group were statistically older, more often
      had a preoperative indwelling ureteral stent and had a mean operative time that
      was 16 minutes longer (p = 0.04). Average stone diameter in the in situ and
      displacement groups was 8 and 10.3 mm., respectively (p = 0.04). In patients with
      radiographic followup greater than 1 month complete success was obtained for 77%
      of stones 1 cm. or less treated in situ versus 89% treated with displacement
      first (p = 0.43). For calculi greater than 1 cm. complete success was obtained
      for 2 of the 7 (29%) treated in situ versus all 7 (100%) treated with
      displacement (p = 0.005). CONCLUSIONS: When treating lower pole calculi 1 to 2
      cm. via ureteroscopy, a higher success rate can be obtained with displacement
      into a more accessible calix before treatment.

PMID- 12050490
TI  - Routine postoperative imaging is important after ureteroscopic stone
      manipulation.
AB  - PURPOSE: Improved fiber optics and advanced intracorporeal lithotripsy devices
      have significantly decreased the incidence of complications during ureteroscopic
      procedures. Despite recent reports suggesting that radiographic imaging may not
      be necessary in all individuals after routine ureteroscopy silent obstruction may
      develop in some, ultimately resulting in renal damage. We determined the
      incidence of postoperative silent obstruction at our institution and assessed the
      need for routine functional radiographic studies after ureteroscopy. MATERIALS
      AND METHODS: We retrospectively reviewed the charts of 320 patients who underwent
      a total of 459 ureteroscopic procedures for renal or ureteral calculi in a 3-year
      period. Complete followup with imaging was available for 241 patients (75%).
      Average patient age was 47.2 years. The variables of interest reviewed included
      preoperative pain, preoperative obstruction, targeted calculous site, stone-free
      rate, postoperative pain and postoperative obstruction. Mean followup was 5.4
      months (range 2 to 43). RESULTS: A total of 241 patients with complete followup
      were identified in this analysis. Preoperative pain was present in 202 patients
      (84%) and 168 (70%) had preoperative obstruction. Overall targeted calculous
      clearance was successful in 73% of the patients and an additional 15.8% had
      residual fragments less than 4 mm. The renal, proximal or mid and distal ureteral
      stone-free rate was 32.1%, 81.9% and 90.5%, while in an additional 46.4%, 6.3%
      and 6.7% of cases, respectively, residual fragments were less than 4 mm. Of the
      241 patients 30 (12.3%) had obstruction postoperatively due to residual stone in
      25 (83.3%), stricture in 3 (10%), edema of the ureteral orifice in 1 (3.3%) and a
      retained encrusted stent in 1 (3.3%). Postoperatively obstruction correlated with
      postoperative pain in 23 of the 30 patients (76.7%). Pain was present
      postoperatively in 30 of the 211 patients (14%) without evidence of ureteral
      obstruction postoperatively. However, silent obstruction developed in 7 patients
      (23.3%) or 2.9% of the total cohort. All 7 patients underwent secondary
      ureteroscopy to alleviate obstruction. A single patient ultimately received
      chronic hemodialysis for renal failure, 1 was lost to followup and in 5 there was
      documented successful resolution of the cause of obstruction. CONCLUSIONS: Our
      analysis suggests that silent obstruction remains a potentially significant
      complication after stone management. Relying on postoperative pain to determine
      the necessity of postoperative imaging places patients at risk for progressive
      renal failure due to unrecognized obstruction. Therefore, we recommend that
      imaging of the collecting system should be performed by excretory urography,
      spiral computerized tomography or ultrasound within 3 months after routine
      ureteroscopic stone treatment to avoid the potential complications of
      unrecognized ureteral obstruction.

PMID- 12050491
TI  - Biological significance of c-met over expression in papillary renal cell
      carcinoma.
AB  - PURPOSE: Hereditary papillary renal cell carcinoma is associated with mutations
      of the c-met proto-oncogene. Similar aberrations have been described at a
      molecular level in up to 13% of sporadic papillary renal cell carcinomas. We
      assessed c-met expression in papillary renal cell carcinomas and evaluated the
      prognostic significance of c-met expression in patients with this tumor.
      MATERIALS AND METHODS: We performed immunohistochemical testing to identify c-met
      expression in archival specimens of 55 papillary renal cell carcinomas in 51
      patients. Only 1 patient reported a family history of renal malignancy. RESULTS:
      We identified c-met protein expression in the cytoplasm and cell membrane of 80%
      and 56% of these tumors, respectively. c-met expression significantly correlated
      with higher stage tumors (p = 0.004) but it was not associated with Fuhrman
      nuclear grade (p = 0.157). A trend toward a higher overall survival rate was
      noted in patients in whom tumors did not express c-met but this association
      failed to achieve statistical significance (p = 0.07). CONCLUSIONS: Our study
      indicates that c-met over expression may be associated with an aggressive
      phenotype in these tumors.

PMID- 12050493
TI  - Transitional cell carcinoma of the bladder in young adults: presentation, natural
      history and outcome.
AB  - PURPOSE: The natural history and prognosis of bladder cancer in young patients is
      not well defined. We analyzed our experience with such patients. MATERIALS AND
      METHODS: The medical records of 74 patients presenting with transitional cell
      carcinoma of the bladder at 40 years and younger were reviewed and compared with
      those of 75 patients diagnosed with bladder transitional cell carcinoma at 65
      years old and older. RESULTS: Median followup was 28.1 months (range 1 to 155)
      and 34.7 (range 1 to 178) in young and old patients, respectively. Initial stage
      distribution was similar with 80% of patients presenting with superficial
      disease. No difference was observed in the disease-free progression or disease
      free recurrence rate among the groups in patients initially presenting with stage
      Ta, Tis or T1 tumors. A significantly higher proportion of older versus younger
      patients underwent cystectomy (54% versus 23%). We did not observe a difference
      in pathological stage distribution or the rate of extravesical disease in young
      and old patients (47% and 45%, respectively). Younger patients who ultimately
      underwent radical cystectomy had significantly lower disease-free survival,
      mainly due to a higher rate of distant metastases than in the older group (41%
      versus 24%). The rate of local recurrence was similar. CONCLUSIONS: Bladder
      transitional cell carcinoma in young adults has a clinical stage distribution and
      natural history similar to that in older patients. Our study suggests that a
      subset of young patients who ultimately undergo radical cystectomy have
      particularly aggressive tumors, portending a poor outcome.

PMID- 12050492
TI  - The influence of pNx/pN0 grouping in a multivariate setting for outcome modeling
      in patients with clear cell renal cell carcinoma.
AB  - PURPOSE: Lymphadenectomy, especially extended lymphadenectomy, is not commonly
      performed in patients undergoing a radical nephrectomy for clear cell renal cell
      carcinoma. Surgeons may sample suspicious regional lymph nodes, but the lymph
      node status of many patients with renal cell carcinoma remains unknown, termed
      stage pNx. Outcome models based on large institutional reviews have been
      criticized for grouping stages pNx and pN0 cases because of concern that the pNx
      category may include unrecognized stages pN1/pN2 disease. We evaluated cancer
      specific survival differences in patients with clear cell renal cell carcinoma
      and a lymph node stage of pNx, pN0 or pN1/pN2. MATERIALS AND METHODS: We searched
      the registry at our institution for patients who underwent radical nephrectomy
      for clear cell histology renal cell carcinoma between 1970 and 1998. Those with
      distant metastases at surgery were excluded from study. Clinical features
      obtained from the medical record included age at surgery, history of tobacco use,
      hypertension and symptomatic disease at presentation. A single urological
      pathologist reviewed all tumor specimens for nuclear grade, tumor necrosis,
      surgical margin status, 1997 tumor stage and lymph node status. These features
      were compared in patients with stages pNx and pN0 tumors. Cox proportional
      hazards models were used to compare cancer specific survival in univariate
      fashion, and after adjusting for tumor stage and grade. RESULTS: The study cohort
      consisted of 1,535 patients with sporadic, unilateral clear cell renal cell
      carcinoma who underwent radical nephrectomy. There were 600 patients (39%) with
      stage pNx, 870 (57%) with stage pN0 and 65 (4%) with stages pN1/pN2 tumors. At an
      average of 4.2 years after surgery 414 patients died of renal cell carcinoma. On
      univariate analysis patients with stage pN0 tumors were significantly more likely
      to die of renal cell carcinoma than those with stage pNx tumors (risk ratio 1.40,
      95% confidence interval 1.12 to 1.75, p = 0.003). However, after adjusting for
      tumor stage and nuclear grade the difference in outcome for stages pNx and pN0
      tumors was not statistically significant (risk ratio 1.07 95% confidence interval
      0.85 to 1.34, p = 0.583). Patients with stage pNx disease were significantly less
      likely to be symptomatic at presentation (p = 0.002), have tumors that were less
      than 5 cm. (p <0.001) and of lower stage (p <0.001) and grade (p = 0.005), and to
      have tumors with necrosis (p = 0.024) than patients with stage pN0 disease.
      CONCLUSIONS: Combining stages pNx and pN0 cases to create outcome prediction
      models after radical nephrectomy for clear cell renal cell carcinoma is
      appropriate in a multivariate setting that includes tumor stage and grade.
      Clinical features available preoperatively and during surgery can help guide the
      decision to perform limited lymph node sampling. When the tumor is 5 cm. or
      greater, shows pathological necrosis or is advanced grade 3 or 4, lymph node
      sampling adds little prognostic information.

PMID- 12050494
TI  - Clinically relevant improvement of recurrence-free survival with 5-aminolevulinic
      acid induced fluorescence diagnosis in patients with superficial bladder tumors.
AB  - PURPOSES: Fluorescence diagnosis induced by 5-aminolevulinic acid enables more
      thorough transurethral resection of superficial bladder carcinoma compared with
      conventional white light. We performed a prospective, single institution,
      randomized trial to investigate whether the residual tumor rate and long-term
      tumor recurrence can be decreased by fluorescence diagnosis. MATERIALS AND
      METHODS: A total of 301 patients underwent transurethral resection of bladder
      tumors with white light or fluorescence diagnosis. Transurethral resection was
      repeated 5 to 6 weeks later to evaluate the residual tumor rate. To determine
      recurrence-free survival patient followup was performed every 3 months by white
      light cystoscopy and urine cytology. Recurrence-free survival was analyzed via
      Kaplan-Meier methods and multivariable Cox regression analysis. RESULTS: A total
      of 191 patients with superficial bladder carcinoma were available for efficacy
      analysis. The residual tumor rate was 25.2% in the white light arm versus 4.5% in
      the fluorescence diagnosis arm (p <0.0001). Median followup in the white light
      arm in 103 cases was 21.2 months (range 4 to 40) compared with 20.5 (range 3 to
      40) in the 88 in the fluorescence diagnosis arm. Recurrence-free survival in the
      fluorescence diagnosis group was 89.6% after 12 and 24 months compared with 73.8%
      and 65.9%, respectively, in the white light group (p = 0.004). This superiority
      proved to be independent of risk group. The adjusted hazard ratio of fluorescence
      diagnosis versus white light transurethral resection was 0.33 (95% confidence
      interval 0.16 to 0.67). CONCLUSIONS: Fluorescence diagnosis is significantly
      superior to conventional white light transurethral resection with respect to the
      residual tumor rate and recurrence-free survival. The differences in recurrence
      free survival imply that fluorescence diagnosis is a clinically relevant
      procedure for decreasing the number of tumor recurrences.

PMID- 12050496
TI  - Dynamic sentinel node biopsy for penile cancer: reliability of a staging
      technique.
AB  - PURPOSE: We determine the value of dynamic sentinel node biopsy for staging
      squamous cell carcinoma of the penis. MATERIALS AND METHODS: A total of 90
      patients with clinically node negative penile cancer were prospectively entered
      in this study. Preoperative lymphoscintigraphy was performed after intradermal
      injection of 99mtechnetium nanocolloid around the primary tumor. The sentinel
      node was intraoperatively identified with the aid of intradermal administered
      patent blue dye and a gamma ray detection probe. Histopathological examination of
      sentinel nodes included serial sectioning and immunohistochemical staining.
      Regional lymph node dissection was performed only if metastasis was found in a
      sentinel node. Median followup was 36 months (range 5 to 95). RESULTS:
      Lymphoscintigraphy visualized 217 sentinel nodes in 159 inguinal regions of 88
      patients. A total of 208 sentinel nodes were intraoperatively identified in 149
      inguinal regions of 88 patients. Sentinel node metastasis was found in 19
      inguinal regions of 18 patients. Four of 8 patients with unilateral clinical
      stage N1 disease had a tumor positive sentinel node on the opposite site.
      Regional recurrence after excision of a tumor negative sentinel node or after
      nonvisualization was seen in 5 patients, resulting in a false-negative rate of
      22% (5 of 23). The 3-year disease specific survival was 98% and 71% for patients
      with a tumor negative or tumor positive sentinel node, respectively (p = 0.0018).
      CONCLUSIONS: Occult lymph node metastases in penile cancer can be detected with a
      sensitivity of about 80% by dynamic sentinel node biopsy, including preoperative
      lymphoscintigraphy, vital dye and a gamma ray detection probe.

PMID- 12050497
TI  - p53 as a new prognostic factor for lymph node metastasis in penile carcinoma:
      analysis of 82 patients treated with amputation and bilateral lymphadenectomy.
AB  - PURPOSE: Gold standard treatment for invasive penile carcinoma remains amputation
      and lymphadenectomy. This procedure has high morbidity and new prognostic factors
      on the incidence of metastasis would help select candidates to lymphadenectomy.
      Mutations in the p53 gene common in several neoplasms can be related to the
      prognosis. We studied 82 patients with penile carcinoma staged according to the
      1978 TNM system who underwent amputation and bilateral lymphadenectomy to
      evaluate the prognostic value of immunohistochemical p53 staining in the primary
      tumor. MATERIALS AND METHODS: Immunoreactivity of p53 was studied with other
      clinicopathological variables, including patient age, stage, histological grade,
      tumor thickness, lymphatic and venous embolization, corpora cavernosa, corpus
      spongiosum and urethral infiltration, and human papillomavirus (HPV) status. We
      also determined its association with lymph node metastasis, the survival rate and
      the risk of death. In addition, we studied the association of p53 and HPV DNA
      with prognosis. All slides were reviewed by 1 pathologist. HPV DNA was detected
      by polymerase chain reaction using GP5/6+ generic primers. p53 expression was
      measured by immunohistochemical testing with monoclonal Clone DO-7 mouse anti
      human p53 protein antibody (Dako A/S, Glostrup, Denmark). The Cox regression
      hazards method was used for multifactorial analysis. RESULTS: Nuclear
      accumulation of p53 was detected in 34 of 82 samples (41.5%). Clinical lymph node
      N stage (p = 0.045), lymphatic (p <0.001) and venous (p = 0.04) embolization by
      neoplastic cells, p53 positivity (p = 0.012) and p53 grade (p = 0.004) were
      significantly associated with lymph node metastasis. Followup was 0.1 to 453
      months (mean 88.7). Multivariate analysis revealed that only lymphatic
      embolization (relative risk 9.4, 95% confidence interval [CI] 2.8 to 31.6) and
      p53 positivity (relative risk 4.8, 95% CI 1.6 to 14.9) were independent factors
      for lymph node metastasis. Patients with negative p53 had significantly better 5
      and 10-year overall survival than those in whom tumors stained positive for p53
      (64.5% and 54.6% versus 30.2% and 26.4%, respectively, p = 0.009). When tumors
      were p53 positive and HPV DNA positive, overall survival was worse. Multivariate
      analysis revealed that only age (relative risk 2.9, 95% CI 1.6 to 5.1) and lymph
      node metastasis (relative risk 3.2, 95% CI 1.8 to 5.8) were independent risk
      factors for death. CONCLUSIONS: Immunoreactivity of p53 is an independent factor
      for lymph node metastasis. The association of positive p53 with positive HPV DNA
      was related to a worse prognosis.

PMID- 12050495
TI  - Evaluation of an unconventional treatment modality with mistletoe lectin to
      prevent recurrence of superficial bladder cancer: a randomized phase II trial.
AB  - PURPOSE: The indication for topic chemotherapy or immunotherapy for well
      differentiated, noninvasive superficial bladder cancer remains controversial.
      Side effects of these treatments promoted use of unconventional therapies with
      cytokines, immunomodulators and mistletoe extracts. However, there are no
      controlled clinical data available on the efficacy of these extracts for bladder
      cancer. We evaluate the influence of subcutaneously applicated mistletoe lectin
      on bladder tumor recurrence after transurethral resection. MATERIALS AND METHODS:
      The study consists of 45 patients with pTa G1-2 bladder cancer treated with
      transurethral resection during a 3-year period. Median patient age was 65 years
      and 33 patients were male. The study cohort was randomly divided into a treatment
      group receiving adjuvant therapy with mistletoe lectin and a control group
      receiving no additional treatment. Patients in the treatment group received
      mistletoe lectin according to schedule 2 weeks after transurethral resection.
      Clinical followup was assessed 3, 6, 9, 12 and 18 months after the initial
      resection, and included uretherocystoscopy. RESULTS: Both study arms comprised
      similar patients with regard to total number of previous tumors (mean 2.6 versus
      2.9), number of primary lesions (14 versus 12) and number of recurrent tumors (8
      versus 11). After followup of 18 months the recurrence-free interval in both
      study arms was similar (p = 0.76) and the total number of recurrences comparable
      (p = 0.48). CONCLUSIONS: Subcutaneous use of mistletoe lectin as adjuvant
      treatment after transurethral resection does not seem to affect the time to first
      recurrence, total number of recurrences or recurrence-free outcome.

PMID- 12050498
TI  - Beneficial impact of a clinical care pathway in patients with testicular cancer
      undergoing retroperitoneal lymph node dissection.
AB  - PURPOSE: Since 1997, we have used a clinical collaborative care pathway for
      patients undergoing retroperitoneal lymph node dissection. We examined its impact
      on perioperative care and outcome. MATERIALS AND METHODS: We examined the records
      of all patients with germ cell carcinoma who underwent retroperitoneal lymph node
      dissection from July 1990 to July 2001. Variables examined included
      clinical/pathological stage, hospital stay, postoperative care and the
      complication rate. RESULTS: A total of 118 patients underwent retroperitoneal
      lymph node dissection for germ cell carcinoma during this period, including 46
      (39%) before pathway implementation in 1997 and 72 patients (61%) after pathway
      implementation. Of the 118 patients 40 (34%) underwent the procedure after
      chemotherapy. This rate remained fairly constant in the period before and after
      pathway initiation (31% and 36%, respectively). After pathway implementation
      fewer patients received a nasogastric tube (94% versus 5%, p <0.001) and had
      complications (26% versus 16%, p = 0.036). Mean hospital stay decreased after
      pathway implementation in all primary and post-chemotherapy retroperitoneal lymph
      node dissection cases (4.2 versus 6.4 days, p <0.005). Although patients who
      underwent the procedure after chemotherapy were more likely to have complications
      than those who underwent a primary procedure, the difference was not
      statistically significant (p = 0.09). CONCLUSIONS: Our collaborative clinical
      care pathway safely and efficiently outlines routine postoperative care and
      significantly decreased hospital stay.

PMID- 12050499
TI  - Evaluation of a new serum testing method for detection of prostate cancer.
AB  - PURPOSE: Serum prostate specific antigen is a highly specific test for diseases
      of the prostate gland but it is not specific for prostate cancer, which can lead
      to unnecessary biopsies. In an effort to find a more specific test, a new testing
      method for detecting prostate cancer based on deglycosylation of cell surface
      proteins and subsequent antibody formation in patients with prostate cancer was
      evaluated. In addition, antibody generation against the peptide fragments chosen
      to represent the cell surface proteins was determined to be cancer associated,
      cancer specific or not related to prostate cancer. MATERIALS AND METHODS:
      Antibody titers to 67 unique peptide sequences representing 41 cell surface
      proteins were determined in 25 men with known prostate cancer (cancer group) and
      34 men without prostate cancer (control group). The titers of the control and
      cancer groups were compared for statistical significance. Additionally, each
      peptide was identified as being cancer specific, cancer associated or not related
      to prostate cancer based on whether patients, controls, both or neither had
      elevated antibody titers. RESULTS: Of the 67 peptides tested 3 demonstrated
      statistical significance between the control and cancer group titers. Using these
      3 informative peptides, 11 of the 25 men known to have prostate cancer had
      positive results (sensitivity 44%), while 2 of the 34 control patients had
      positive results (specificity 94%). Of the peptides with significantly different
      titers in patients and controls 2 of the 19 cell surface proteins known to be
      present in prostate cancer were represented. No peptides were found to generate
      antibodies only in patients with cancer (cancer specific), while 3 were cancer
      associated (increased in cancer and controls). CONCLUSIONS: A new approach to
      testing for prostate cancer, although lacking in sensitivity, appears to be
      highly specific. The high specificity of this test suggests that when combined
      with a highly sensitive test, such as prostate specific antigen, screening could
      be significantly improved.

PMID- 12050500
TI  - Prediction of pathological stage in patients with clinical stage T1c prostate
      cancer: the new challenge.
AB  - PURPOSE: We developed an algorithm for predicting the likelihood of organ
      confined disease in patients with clinical stage T1c prostate cancer using biopsy
      pathology, computer assisted image analysis and serum prostate specific antigen
      (PSA). MATERIALS AND METHODS: Of the 557 consecutive men enrolled in this study
      between October 1998 and January 2000 scheduled for radical prostatectomy at a
      single institution 386 (69%) presented with clinical stage T1c disease. Study
      exclusion criteria included neoadjuvant hormonal treatment with luteinizing
      hormone-releasing hormone, antiandrogen or 5alpha-reductase inhibitors.
      Preoperative serum, biopsy histology slides, clinical demographic information,
      prostatectomy pathology and prostate weight data were obtained. Biomarkers
      assessed included total PSA, complexed PSA, free PSA, the free-to-total PSA
      ratio, quantitative nuclear grade determined by image analysis, complexed PSA
      density, and biopsy Gleason grade and score. To determine patient specific
      quantitative nuclear grade values, images from approximately 125 cancer nuclei
      were captured per patient from the area of the biopsy section with the highest
      Gleason score. The variance in 60 nuclear size, shape and chromatin texture
      descriptors was calculated for each gallery of nuclei. Logistic regression was
      done to determine the most accurate combination of variables for predicting organ
      confined prostate cancer. RESULTS: Complete results and data were available on
      255 of the 386 men (66%) with an average age plus or minus standard deviation of
      58.8 +/- 6 years who had stage T1c disease, including 49 (19%) with
      pathologically nonorgan confined disease. Logistic regression analysis revealed
      that quantitative nuclear grade, biopsy Gleason score, total PSA, the calculated
      free-to-total PSA ratio, complexed PSA and complexed PSA density were
      univariately significant for predicting organ confined disease (p <0.05). On
      backward stepwise logistic regression only quantitative nuclear grade, complexed
      PSA density and Gleason score remained in a model yielding an area under the
      receiver operating characteristics curve of 82.4%. CONCLUSIONS: The quantitative
      nuclear grade biomarker was the strongest independent predictor of pathological
      stage in men with clinical stage T1c prostate cancer when combined with biopsy
      Gleason score and complexed PSA density data.

PMID- 12050501
TI  - Sextant prostate biopsies predict side and sextant site of extracapsular
      extension of prostate cancer.
AB  - PURPOSE: We examined the ability of sextant prostate biopsies in combination with
      other preoperative data to predict side and sextant site of prostate cancer
      extracapsular extension in a large cohort of patients. MATERIALS AND METHODS: We
      examined 223 contemporary cases of prostate cancer managed by radical
      prostatectomy. Using logistic regression analysis, we determined whether patient
      age, Gleason score, clinical stage, prostate specific antigen, number of positive
      sextants, biopsy location or percent of biopsy cores positive for cancer in a
      sextant site, side and overall gland was predictive of location of pathological
      extracapsular extension into periprostatic tissue. RESULTS: Of 41 of the 223
      (18%) patients with nonorgan confined disease extracapsular extension was
      localized to 45 sextant sites in 36 (apex 8, mid 22, base 15) while only side of
      extension was known in 5. In a multivariate analysis the best predictors of the
      risk of extracapsular extension on a side were average percent biopsy cores
      positive for cancer overall 15 or greater (odds ratio 8.4, p <0.0001) and average
      from 3 ipsilateral biopsies 15 or greater (odds ratio 7.4, p <0.0001). When used
      in combination these 2 factors yielded a model with a positive predictive value
      of 37% and a negative predictive value of 95%. Sextant specific percent biopsy
      cores positive for cancer was predictive of risk of extracapsular extension in a
      sextant (odds ratio 2.5, p = 0.020). CONCLUSIONS: Our data demonstrate that
      average overall and per side percent biopsy cores positive for cancer is a
      significant predictor of risk of extracapsular extension on a side. Sextant
      specific percent biopsy cores positive for cancer is predictive of sextant site
      of extension. The high negative predictive value of the side specific model
      identifies patients who are good candidates for nerve sparing surgery.

PMID- 12050502
TI  - Improved risk stratification for biochemical recurrence after radical
      prostatectomy using a novel risk group system based on prostate specific antigen
      density and biopsy Gleason score.
AB  - PURPOSE: Previous studies have suggested that prostate specific antigen (PSA)
      density is a significant independent predictor of biochemical failure after
      primary therapy. We determined whether pathological PSA density using surgical
      weight of the radical prostatectomy specimen was an independent predictor of
      adverse pathological features or biochemical recurrence after radical
      prostatectomy. We also examined whether combining pathological PSA density with
      biopsy Gleason score improved risk stratification compared with serum PSA and
      biopsy Gleason score for predicting PSA recurrence after prostatectomy. MATERIALS
      AND METHODS: Multivariate analysis was used to determine whether pathological PSA
      density was an independent predictor of adverse pathology or PSA recurrence after
      radical prostatectomy in 325 patients treated at a Veterans Affairs medical
      center. Cutoff points of pathological PSA density were generated to identify
      patients at various risks for biochemical recurrence. These cutoffs were combined
      with biopsy Gleason cutoff points 2 to 6, 7 and 8 to 10 to generate a risk
      stratification system that was compared with a previous risk stratification
      system using PSA and biopsy Gleason score cutoff points. The validity of the risk
      stratification system using pathological PSA density and biopsy Gleason score was
      evaluated in another cohort of 490 patients treated with radical prostatectomy at
      a tertiary care medical center. RESULTS: Pathological PSA density was an
      independent predictor of positive surgical margins (p <0.001), nonorgan confined
      disease (p <0.001), seminal vesicle invasion (p = 0.003) and biochemical
      recurrence after radical prostatectomy (p <0.001). The cutoff points for
      pathological PSA density of less than 0.3, 0.3 to 0.7 and greater than 0.7
      ng./ml./gm. separated patients into 3 distinct groups at increasing risk for
      biochemical failure after radical prostatectomy (p <0.001). Pathological PSA
      density cutoffs combined with biopsy Gleason score cutoffs 2 to 6, 7 and 8 to 10
      provided better risk stratification for biochemical failure than cutoffs based on
      a combination of PSA and biopsy Gleason score in patients treated at the Veterans
      Affairs (hazards ratio 3.04, confidence interval 2.25 to 4.11, p <0.001) and
      tertiary care (hazards ratio 2.38, confidence interval 1.78 to 3.18, p <0.001)
      medical centers. CONCLUSIONS: Pathological PSA density was a strong predictor of
      advanced pathology and biochemical failure after radical prostatectomy.
      Pathological PSA density combined with biopsy Gleason score defined a novel risk
      group system that improved risk stratification compared with a combination of PSA
      and biopsy Gleason score. These results were validated in another cohort of
      patients treated with radical prostatectomy at a tertiary care medical center.
      Further studies are required using PSA density values calculated from
      preoperative transrectal ultrasound measurements to determine whether a
      combination of PSA density and biopsy Gleason score provides significant
      pretreatment risk stratification.

PMID- 12050503
TI  - Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided
      prostate biopsy: a double-blind randomized controlled study.
AB  - PURPOSE: We performed a randomized, placebo controlled double-blind trial to
      evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom),
      that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound
      guided prostate biopsy. MATERIALS AND METHODS: Patients referred for transrectal
      ultrasound guided prostate biopsy for the first time as an outpatient procedure
      were recruited subject to exclusion criteria and randomized to breathe Entonox or
      air via similar breath activated devices. At the end of the procedure patients
      completed a visual pain analog scale. Patients who refused study participation
      also completed the visual analog pain scale to assess the placebo effect of
      receiving gas through a mask. RESULTS: A total of 110 patients were studied.
      Statistical analysis using 1-way analysis of variance showed a highly significant
      difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001).
      This significant decrease in pain was noted in the Entonox versus air and Entonox
      versus placebo groups. There was no significant difference in the air and placebo
      groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy
      during the procedure, which resolved at completion of the procedure. In this
      group 49 patients would undergo this procedure again if needed. In 2 of the 45
      patients in the group receiving air the procedure was abandoned due to pain,
      while another 19 would prefer more analgesia and 2 would prefer general
      anesthesia if the procedure was to be repeated. CONCLUSIONS: Our study shows that
      Entonox is a safe, rapidly acting and effective form of analgesia for the pain of
      prostate biopsy. We believe that it should be the analgesia of choice for this
      procedure.

PMID- 12050504
TI  - Blood flow, pressure and compliance in the male human bladder.
AB  - PURPOSE: The regulation of human bladder blood flow during filling is poorly
      understood. We characterized changes in bladder blood flow with filling and
      examined the relationship of bladder compliance and blood flow. MATERIALS AND
      METHODS: A total of 17 awake male patients underwent saline cystometry followed
      by cystoscopy while under local anesthesia, during which a laser Doppler flow
      probe was placed into the posterior bladder wall detrusor. Systemic blood
      pressure, bladder blood flow and intravesical pressure were measured with the
      bladder empty and filled to 25%, 50%, 75% and 100% of awake maximum cystometric
      capacity as well as immediately after bladder drainage. RESULTS: Mean bladder
      blood flow was lowest in the empty bladder and increased with bladder filling. A
      mean peak flow plus or minus standard error of 7.6 +/- 1.1 ml. per minute per 100
      gm. tissue was observed at volumes greater than 75% but less than 100% of maximum
      cystometric capacity. At 100% maximum cystometric capacity mean intravesical
      pressure increased by 73% from 25.2 to 43.5 cm. water and bladder blood flow
      decreased by 36%. Rapid bladder drainage was associated with a rebound in mean
      bladder blood flow to approximately 1.6 times baseline. Bladder compliance
      calculated for the whole filling curve positively correlated with bladder blood
      flow (p = 0.025), that is low compliance was associated with low blood flow.
      CONCLUSIONS: Human bladder blood flow tends to increase with increasing volume
      and pressure, and depends largely on local regulation. At capacity bladder blood
      flow is significantly decreased. Immediately after bladder drainage there is a
      rebound in blood flow, allowing reperfusion to occur. Decreased bladder blood
      flow and decreased bladder wall compliance correlated strongly, suggesting that
      ischemia may lead to structural changes in the bladder wall.

PMID- 12050505
TI  - A qualitative ultrastructural study of the hypocontractile detrusor.
AB  - PURPOSE: It has been proposed that precise and specific ultrastructural patterns
      exist in the dysfunctional human detrusor. We evaluated ultrastructural changes
      in the hypocontractile detrusor and examined the technique of detrusor muscle
      biopsy and its clinical application. MATERIALS AND METHODS: After clinical and
      urodynamic evaluation 19 male and 2 female patients with severe hypocontractility
      were entered into this prospective study. All patients had a post-void residual
      urine volume of consistently greater than 300 ml. and were classified as weak or
      very weak according to the Schafer nomogram. Multiple biopsies were obtained with
      the patient under general anesthesia using the cold cup technique. Subsequent
      specimens were processed for electron microscopy using standard methods. Biopsies
      were also obtained from 6 controls with normal voiding parameters. RESULTS: Cold
      cup detrusor biopsy provided muscle of sufficient quality for detailed electron
      microscopic analysis in 26 of the 27 specimens obtained. Previously described
      criteria of the degeneration pattern were present in all cases of severe
      hypocontractility. These criteria include widespread disruptive muscle cell
      profiles with sarcoplasmic vacuolation, disruption of cell organelles and
      ultimately cell lysis. These features were evident in more than half of the
      randomly studied fields. In addition, 7 patients had an indistinct muscle
      fascicle cell arrangement with excessive deposits of collagen and elastic fibers
      between widely separated muscle cells and in the interstitium. It was suggested
      that these features represent the hyperelastosis pattern in the chronically over
      distended bladder. These morphological appearances were not present in any
      controls. CONCLUSIONS: This early study would appear to support a morphological
      basis for detrusor hypocontractility and it reinforces the feasibility of
      electron microscopy as a potential diagnostic tool. The hypocontractile detrusor
      has distinct ultrastructural appearances that are easily distinguishable from
      those of the normal age matched detrusor.

PMID- 12050506
TI  - The relationship of detrusor instability and symptoms with objective parameters
      used for diagnosing bladder outlet obstruction: a prospective study.
AB  - PURPOSE: Detrusor instability is a common urodynamic finding in patients with
      prostatic obstruction. In prospective fashion we evaluated detrusor instability
      in patients with lower urinary tract symptoms attributable to benign prostatic
      hyperplasia and determined its possible association with the degree of
      obstruction. MATERIALS AND METHODS: A total of 459 men with a mean age plus or
      minus standard deviation of 60.4 +/- 9.4 years who were investigated for lower
      urinary tract symptoms at our facility answered an Arabic standardized version of
      International Prostate Symptom Score and underwent simple uroflowmetry,
      outpatient cystoscopy and transrectal ultrasound. Invasive urodynamics, including
      filling and voiding cystometry, was done with pressure flow analysis according to
      the Schafer nomogram. Statistical significance was tested by the Mann-Whitney U
      and Wilcoxon rank sum tests. RESULTS: Of the 459 patients 108 (23.5%) had
      detrusor instability. Instability significantly affected patient symptom score
      and conception of quality of life. Moreover, instability significantly affected
      the degree of obstruction, as measured by the maximum flow rate, post-void
      residual urine, prostate volume and Schafer grade of obstruction. CONCLUSIONS:
      Detrusor instability affects patient symptoms and quality of life. It also
      signifies a more severe degree of obstruction in male patients with lower urinary
      tract symptoms and bladder outlet obstruction due to benign prostatic
      hyperplasia.

PMID- 12050507
TI  - Lower urinary tract symptoms in young men: videourodynamic findings and
      correlation with noninvasive measures.
AB  - PURPOSE: In a prospective manner we sought to determine the cause of lower
      urinary tract symptoms in young men and whether noninvasive testing and symptoms
      scores are useful in deciding which patients to evaluate with videourodynamics.
      MATERIALS AND METHODS: We evaluated 85 men 18 to 45 years old with lower urinary
      tract symptoms. Patients with a history of known neurological disease or urethral
      stricture were excluded from the study. Patients were evaluated with the American
      Urological Association (AUA) symptom index, noninvasive uroflowmetry post-void
      residual and videourodynamics, and classified by specific urodynamic diagnoses.
      Noninvasive uroflowmetry (normal versus abnormal), post-void residual and AUA
      symptom index (total, voiding and storage scores) were evaluated as predictors of
      urodynamic abnormalities. RESULTS: Mean patient age was 35.1 (range 18 to 45) and
      mean symptom duration was 53.8 months. Mean AUA scores were total 19.3, voiding
      10.8 and storage 8.5. Videourodynamic diagnoses were primary bladder neck
      obstruction in 40 (47%) cases, dysfunctional voiding in 12 (14%), impaired
      contractility in 8 (9%), sensory urgency in 7 (8%), detrusor instability alone in
      5 (6%), detrusor instability and impaired contractility in 1 (1%), external
      detrusor-sphincter dyssynergia in 1 (1%) and normal in 5 (6%). Of these patients,
      9 could not void during urodynamics and in 6 (7%) no urodynamic diagnosis was
      made. Videourodynamics were not considered helpful in patients with a normal or
      nondiagnostic study or sensory urgency only (group 1) but were helpful or
      diagnostic in the remaining patients (group 2). Only 5 of 18 patients (28%) in
      group 1 had an abnormal uroflow compared to 56 of 67 (84%) in group 2 (p
      <0.0001). Mean post-void residual volumes were not different between the 2 groups
      (40.3 versus 40.0 ml.). Mean total and storage symptom scores were also not
      different between the 2 groups but voiding scores were significantly higher in
      group 2 (11.5 versus 8.3, p <0.03). CONCLUSIONS: Lower urinary tract symptoms in
      young men have a variety of underlying causes. Videourodynamics is an extremely
      helpful diagnostic test especially in men with abnormal uroflow and high voiding
      scores.

PMID- 12050508
TI  - Prevalence of symptoms related to interstitial cystitis in women: a population
      based study in Finland.
AB  - PURPOSE: Interstitial cystitis is a chronic inflammatory bladder disease. Despite
      intensive research its prevalence, etiology, diagnosis and appropriate treatment
      remain elusive. We estimated the prevalence of urinary symptoms related to
      interstitial cystitis in women in Finland. MATERIALS AND METHODS: We randomly
      selected 2,000 study participants 18 to 71 years old from the Finnish population
      register. The prevalence of urinary symptoms was evaluated using the validated
      O'Leary-Sant interstitial cystitis symptom and problem index questionnaire, which
      was mailed to subjects. Women with high (12 or greater) symptom and problem
      scores, including nocturia 2 or greater, pain 2 or greater, and excluding urinary
      infection and pregnancy, were considered most likely to have interstitial
      cystitis. RESULTS: The response rate after 2 mailings was 67.2% (1,343
      respondents). After further exclusions 1,331 women (66.6%) comprised the final
      study group. Of these 1,331 respondents 11 (0.8%) reported severe symptoms and
      problems (12 or greater), including 6 (0.45%) who fulfilled the criteria for
      probable interstitial cystitis. CONCLUSIONS: The prevalence of urinary symptoms
      corresponding to probable interstitial cystitis is 450/100.000 (95% confidence
      interval 100 to 800), which is an order of magnitude higher than previously
      reported.

PMID- 12050509
TI  - Polypropylene mesh tape for stress urinary incontinence: complications of
      urethral erosion and outlet obstruction.
AB  - PURPOSE: Gynecare tension-free vaginal tape (Ethicon, Inc., New Brunswick, New
      Jersey) is a propylene mesh tape recently introduced in the United States as
      minimally invasive treatment for stress urinary incontinence. We report the
      combined experience at 3 tertiary care institutions with graft erosion and
      bladder outlet obstruction after procedures performed elsewhere. MATERIALS AND
      METHODS: We reviewed the records of 5 patients with complications who presented
      to 1 of 3 institutions after polypropylene mesh tape placement. All pertinent
      information was obtained from the medical records and the operating surgeon at
      the referring institution. RESULTS: Treatment was required in 2 patients with
      urethral erosion, 1 with vaginal and bladder erosion, and 2 with bladder outlet
      obstruction. Common presenting symptoms included urge, urge incontinence and
      gross hematuria. Cystoscopy showed polypropylene graft erosion at the urethra or
      through the bladder wall. Each patient required explantation of the polypropylene
      mesh tape and further surgery to restore continence. The graft was divided
      transvaginally in the 2 patients presenting with outlet obstruction. Urge
      incontinence resolved and they returned to complete spontaneous voiding.
      CONCLUSIONS: High clinical suspicion is necessary when evaluating patients
      presenting with urinary symptoms after polypropylene mesh tape placement. Bladder
      outlet obstruction and possible graft erosion should be considered.

PMID- 12050510
TI  - Pathological findings of gynecologic organs obtained at female radical
      cystectomy.
AB  - PURPOSE: Historically anterior pelvic exenteration has been the recommended
      treatment for invasive urothelial carcinoma in women undergoing radical
      cystectomy. We evaluated the pathological features of reproductive organs removed
      during exenteration to determine the incidence of malignant pathology in these
      organs and the need for removal. MATERIALS AND METHODS: We reviewed the records
      of all patients who underwent radical cystectomy between January 1994 and
      December 2000. Of these 382 patients, we identified 68 females who underwent
      radical cystectomy for urothelial carcinoma. We reviewed preoperative, operative
      and pathological findings, including bladder, lymph nodes, uterine and adnexal
      pathology, in these female patients. RESULTS: Median patient age was 64 years
      (range 35 to 86). Gynecologic organs were present in 40 of the 68 surgical
      specimens (59%). The reasons for absent gynecologic pathology were previous
      hysterectomy in 26 cases and the preservation of organs during orthotopic urinary
      diversion creation in 2. Malignancy was identified in 3 specimens, including
      invasive urothelial carcinoma in 2 (5%). In these 2 cases invasion was clearly
      identified intraoperatively. Low grade stromal sarcoma of the uterus was present
      in 1 specimen (2%). CONCLUSIONS: In the absence of clinical suspicion radical
      hysterectomy at cystectomy rarely improves cancer control. Furthermore, secondary
      malignancies are rare. The functional impact of preserving gynecologic organs is
      a subject of ongoing study.

PMID- 12050511
TI  - Analytical accuracy and reliability of commonly used nutritional supplements in
      prostate disease.
AB  - PURPOSE: We determine the analytical accuracy and reliability of commonly used
      nutritional supplements for prostate disease by comparing the amounts of active
      ingredients of several brands of vitamin E, vitamin D, selenium, lycopene and saw
      palmetto. We also compared the amounts of active compound in different lots of
      the same brand to determine the consistency of the manufacturing process.
      MATERIALS AND METHODS: Samples purchased at pharmacies and specialty stores were
      sent for independent chemical analysis. The measured dose was compared to the
      stated dose on the product label. Analysis of variance was performed to test for
      significance in interlot reliability. RESULTS: Vitamin E (7 samples) and selenium
      (5) were within a range of -41% to +57% and -19% to +23% of the stated dosage,
      respectively. All vitamin D brands (4 samples) were within 15% of the stated
      dose. Saw palmetto (6 samples) were within a range -97% to +140% of the stated
      dosages with 3 containing less than 20% of the stated dosages. Lycopene brands
      were between -38% and +143% of stated dosages. Among the reliability assays 1 of
      3 brands of vitamin E, 1 of 2 brands of selenium and 1 of 2 brands of saw
      palmetto demonstrated statistical differences in interlot dosage (p <0.0055,
      approximate 20% to 25% differences in dose). The 1 assayed form of vitamin D was
      reliable between lots. CONCLUSIONS: Commonly used nutritional supplements for
      prostate disease vary widely in measured dose. Saw palmetto demonstrated
      tremendous variability with some samples containing virtually no active
      ingredients. In contrast, the more regulated substances we measured, such as
      vitamins and minerals, demonstrated less variation.

PMID- 12050512
TI  - A comparison of techniques for eliciting patient preferences in patients with
      benign prostatic hyperplasia.
AB  - PURPOSE: We compared the Health Utility Index (HUI), EuroQol (EQ-5D) and time
      trade-off methods to identify the most suitable technique for collecting
      preference data in a clinical trial of patients with benign prostatic hyperplasia
      (BPH). MATERIALS AND METHODS: A total of 29 men with symptomatic BPH were
      interviewed by a single trained interviewer who collected demographic data and
      administered EQ-5D and time trade-off questionnaires. Participants self
      administered the HUI and a symptom severity index, the International Prostate
      Symptom Score (I-PSS) questionnaire. Utility values for current patient health
      states obtained from the HUI, EQ-5D and time trade-off questionnaires were
      compared and their relationship with I-PSS data was examined using Spearman's
      correlation coefficients. Administration time and patient assessments of the
      relevance of the questions were also compared for the 3 methods. RESULTS:
      Although mean utility values for HUI, EQ-5D and 1-year time trade-off were
      similar, only utility values elicited using time trade-off with a 1-year time
      frame significantly correlated with symptom scores. The 1 and 10-year time trade
      off derived values were reasonable predictors of the I-PSS with multiple
      correlation coefficient values of 0.379 and 0.265, respectively. All participants
      indicated that the HUI and EQ-5D were appropriate for assessing BPH, while
      approximately 10% considered time trade-off questions irrelevant. Average
      completion time for the HUI, time trade-off and EQ-5D questionnaires was 31, 25
      and 10 minutes, respectively. CONCLUSIONS: Because only time trade-off resulted
      in utility values that significantly correlated with symptom scores, we recommend
      its use for estimating utility in clinical trials of BPH.

PMID- 12050513
TI  - An extract from the bark of Aspidosperma quebracho blanco binds to human penile
      alpha-adrenoceptors.
AB  - PURPOSE: We determined whether an extract from the bark of the tree Aspidosperma
      quebracho blanco, which is used as a prescription drug to treat erectile
      dysfunction in some countries, can bind to human penile alpha1 and alpha2
      adrenoceptors, and cloned human alpha-adrenoceptor subtypes. MATERIALS AND
      METHODS: Competition binding studies were performed with alpha1 and alpha2
      adrenoceptors with the extract and 4 subfractions prepared from it using
      [3H]prazosin (New England Nuclear, Dreieich, Germany) and [3H]RX 821002 (2
      methoxy-idazoxam) (Amersham, Braunschweig, Germany) as the radioligands,
      respectively. RESULTS: In a concentration dependent manner the extract inhibited
      2-methoxy-idazoxam binding to human penile alpha2-adrenoceptors. Somewhat less
      potently it inhibited [3H] prazosin binding to penile alpha1-adrenoceptors. The
      extract also inhibited binding to cloned alpha2-adrenoceptors more potently than
      to alpha1-adrenoceptors but did not discriminate among subtypes. Subfraction B
      was more potent than the others for all cloned alpha1-adrenoceptor subtypes and
      much more potent at all penile and all cloned alpha2-adrenoceptor subtypes. This
      fraction largely contained yohimbine, whereas the other fractions were devoid of
      yohimbine. Based on yohimbine competition binding experiments with penile and
      cloned alpha1 and alpha2-adrenoceptors, it appears that the inhibitory effects of
      the abstract and its subfractions can largely be explained by its yohimbine
      content. CONCLUSIONS: An alpha-adrenoceptor mediated component of the pro
      erectile effects of Aspidosperma quebracho blanco bark extract may predominantly
      be caused by its yohimbine content. The alpha-adrenoceptor independent, pro
      erectile effects of the extract could not be determined from this study.

PMID- 12050514
TI  - Health related quality of life assessment after radical cystectomy: comparison of
      ileal conduit with continent orthotopic neobladder.
AB  - PURPOSE: Health related quality of life after urinary diversion has been
      increasingly recognized as an important outcome measure. However, few studies
      have directly compared patients with an ileal conduit with those with a continent
      orthotopic neobladder and even fewer have used validated quality of life
      instruments. Therefore, we compared health related quality of life in patients
      who underwent neobladder versus ileal conduit creation using validated
      questionnaires. MATERIALS AND METHODS: We mailed 2 validated questionnaires that
      are measures of health related quality of life, namely the RAND 36-Item Health
      Survey (SF-36) and Functional Assessment of Cancer Therapy-General (FACT-G), to
      patients who underwent radical cystectomy for urothelial carcinoma between
      January 1995 and December 1999. Statistical analysis was performed, including
      univariate and multivariate analysis. RESULTS: A total of 112 patients were
      available for assessment. A total of 72 (64%) questionnaires were returned,
      including 23 (32%) and 49 (68%) from patients with an ileal conduit and
      neobladder, respectively. On the SF-36 questionnaire there were significant
      univariable relationships between treatment and age (p <0.001 and 0.01,
      respectively). Younger patients and those with a neobladder had higher health
      related quality of life scores, including significant differences in 5 of the 9
      SF-36 domains (general health, physical functioning, physical health, social
      functioning and energy/fatigue). There was no relationship between health related
      quality of life and the final pathological stage (p = 0.25). On multivariate
      analysis adjusting for age led to a suggestive but nonsignificant difference in
      health related quality of life scores favoring neobladders (p = 0.09). On the
      FACT-G there were no significant differences in health related quality of life
      due to treatment (p = 0.28), pathological stage (p = 0.5), age (p = 0.72) or
      current disease status (p = 0.27). On the FACT-G 2 of the 4 domains (emotional
      and functional well-being) were significantly in favor of neobladders. Overall
      satisfaction was high in the 2 groups with 96% and 85% of patients with a
      neobladder and ileal conduit, respectively, reporting that they would make the
      same choice of diversion. CONCLUSIONS: Based on validated health related quality
      of life instruments these findings suggest that patients with an orthotopic
      neobladder have marginal quality of life advantages over those with an ileal
      conduit. However, differences in health related quality of life in the 2 types of
      urinary diversion are confounded by age since patients who underwent orthotopic
      diversion were younger and as a result of age would be expected to have a higher
      health related quality of life score. A prospective longitudinal study of health
      related quality of life after adjusting for differences in age among patients
      undergoing urinary diversion is currently underway to extend further these
      observations.

PMID- 12050515
TI  - Distressful symptoms and well-being after radical cystectomy and orthotopic
      bladder substitution compared with a matched control population.
AB  - PURPOSE: We compared subjective quality of life, well-being, urinary tract
      symptoms and distress in patients after radical cystectomy and orthotopic urinary
      reconstruction with those in a matched control population. MATERIALS AND METHODS:
      Included in this study were 101 consecutive recurrence-free patients who
      underwent radical cystectomy and orthotopic bladder substitution with an ileal
      urethral Kock neobladder at Herlev Hospital with a minimum followup of 1 year. A
      frequency matched control group comprising 147 individuals was selected from the
      same geographical region. Information was collected by an anonymous postal
      questionnaire and analyzed externally in Sweden. RESULTS: The prevalence of low
      or moderate psychological well-being (32% versus 36%) and subjective quality of
      life (30% versus 38%), and high or moderate anxiety (23% versus 18%) and
      depression (26% versus 37%) was similar in patients with an orthotopic neobladder
      and population controls. Patients with a neobladder felt as attractive as the
      control population. Of the operated men 94% had erectile dysfunction compared
      with 48% of controls. Daytime and nighttime urinary frequency was similar in
      patients and controls (3% and 3%, and 15% and 13%, respectively), while the
      prevalence of urinary leakage at least once monthly was higher in patients (18%
      versus 5%). Intermittent self-catheterization was performed by 26% of patients
      with a neobladder. Urinary tract infection (14% versus 6%) was more common and
      the prevalence of distressful bowel symptoms (14% versus 9%) was slightly more
      common in patients than in controls. CONCLUSIONS: Well-being and subjective
      quality of life in patients after radical cystectomy and orthotopic bladder
      substitution were similar to those in a matched control population.

PMID- 12050516
TI  - Hand assisted laparoscopic radical nephrectomy for renal cell carcinoma with
      inferior vena caval thrombus.
AB  - PURPOSE: To our knowledge we present the initial clinical report of hand assisted
      laparoscopic radical nephrectomy for renal cell carcinoma with tumor thrombus
      extending into the inferior vena cava. MATERIALS AND METHODS: A 76-year-old man
      was referred to our medical center with a 12.5 x 10 cm. stage T3b right renal
      tumor extending into the inferior vena cava. The caval thrombus was limited and
      completely below the level of the hepatic veins. After preoperative renal
      embolization via the hand assisted transperitoneal approach the right kidney was
      completely dissected with the renal hilum. Proximal and distal control of the
      inferior vena cava was obtained with vessel loops and a single lumbar vein was
      divided between clips. An endoscopic Satinsky vascular clamp was placed on the
      inferior vena cava just beyond its juncture with the right renal vein, thereby,
      encompassing the caval thrombus. The inferior vena cava was opened above the
      Satinsky clamp and a cuff of the inferior vena cava was removed contiguous with
      the renal vein. The inferior vena cava was repaired with continuous 4-zero
      vascular polypropylene suture and the Satinsky clamp was then removed. A
      literature search failed to reveal any similar reports of laparoscopic radical
      nephrectomy for stage T3b renal cell cancer. RESULTS: Surgery was completed
      without complication with an estimated 500 cc blood loss. Pathological testing
      confirmed stage T3b grade 3 renal adenocarcinoma with negative inferior vena
      caval and soft tissue margins. CONCLUSIONS: The introduction of vascular
      laparoscopic instrumentation and the hand assisted approach enabled us to extend
      the indications for laparoscopic radical nephrectomy to patients with minimal
      inferior venal caval involvement.

PMID- 12050517
TI  - Laparoscopic ileovesicostomy.
AB  - PURPOSE: We present our initial experience with laparoscopic ileovesicostomy for
      managing neurogenic bladder. MATERIALS AND METHODS: A 5 port transperitoneal
      approach was used for laparoscopic ileovesicostomy. After bladder preparation a
      17 cm. ileal segment was harvested and used as the urinary conduit. Ileovesical
      anastomosis was formed using intracorporeal suturing and knot tying techniques.
      RESULTS: Operative time was 4 hours. Blood loss was less than 100 ml. Physical
      activity and oral intake resumed on postoperative day 1 and the patient was
      discharged home on postoperative day 3. The postoperative narcotic requirement
      was 4 mg. morphine sulfate equivalent. There were no intraoperative or
      postoperative complications. CONCLUSIONS: Laparoscopic ileovesicostomy in this
      initial experience was associated with acceptable operative time and minimal
      postoperative morbidity. It may serve as an excellent minimally invasive
      alternative to conventional open ileovesicostomy.

PMID- 12050518
TI  - Urethral substitution using an intestinal free flap: a novel approach.
AB  - PURPOSE: Patients who have extensive stricture disease, those in whom hypospadias
      repair fails and those who sustain significant urethral trauma pose a
      reconstructive challenge for genitourinary surgeons. We developed an additional
      reconstructive option for men with a severely diseased urethra when grafting
      procedures and local tissue flaps have failed or are otherwise contraindicated.
      MATERIALS AND METHODS: A genitourinary reconstructive team performed novel
      intestinal free flap substitution urethroplasty in 2 patients. A segment of
      jejunum is harvested on a vascular pedicle and plicated into an appropriate size
      urethral substitute. Microvascular anastomoses allow this segment to remain
      viable and functional. The technical aspects of repair and surgical
      considerations are detailed. RESULTS: The 2 patients have a satisfactory
      functional and cosmetic outcome. At short followup the urethral lumen remained
      patent and the intestinal urethra remained viable and intact. Both patients have
      good urinary streams and are able to void in the standing position. CONCLUSIONS:
      This initial experience in 2 patients indicates that intestinal segment urethral
      substitution may be considered within the reconstructive armamentarium of
      genitourinary surgeons when more conventional options have failed or are
      contraindicated. Continued vigilant followup is necessary to detail any secondary
      complications. In addition, further experience with this technique by other
      surgeons would help determine its overall usefulness.

PMID- 12050519
TI  - Ureteral stenting via an ileal conduit using a gastroscope.
AB  - PURPOSE: We describe a technique that facilitates retrograde ureteral cannulation
      and stenting in patients with an ileal conduit. MATERIALS AND METHODS: A standard
      flexible gastroscope is inserted into the ileal conduit. Guide wires are passed
      into the ureters under direct vision. Stents are inserted over the guide wires
      with the aid of the image intensifier. RESULTS: The technique was used repeatedly
      in 1 patient with a complex history who had ureteral strictures. The procedure is
      technically easy and it was successful on each occasion. CONCLUSIONS: A fiber
      optic gastroscope may have advantages over conventional urological
      instrumentation for inserting ureteral stents in patients with an ileal conduit.
      This novel, simple technique is less invasive than percutaneous stenting and
      easier than fluoroscopic cannulation of the ureters. It is readily repeated.

PMID- 12050520
TI  - Radio frequency ablation induced acute renal failure.

PMID- 12050521
TI  - Desmopressin induced hyponatremia and seizures after laparoscopic radical
      nephrectomy.

PMID- 12050522
TI  - Spontaneous rupture of adrenal pheochromocytoma.

PMID- 12050523
TI  - Rapidly progressive malignant epithelioid angiomyolipoma of the kidney.

PMID- 12050524
TI  - Small cell prostate cancer with anti-Hu positive peripheral neuropathy.

PMID- 12050525
TI  - Resistance to luteinizing hormone releasing hormone agonist therapy for
      metastatic prostate cancer.

PMID- 12050527
TI  - Ureteritis cystica presenting as a retractile ureteral polyp.

PMID- 12050526
TI  - Decreasing prostate specific antigen value leading to the diagnosis of a
      pituitary adenoma.

PMID- 12050528
TI  - Endoscopic treatment of bladder perforation after tension-free vaginal tape
      procedure.

PMID- 12050530
TI  - Re: Editorial comment on open donor, laparoscopic donor and hand assisted
      laparoscopic donor nephrectomy: a comparison of outcomes.

PMID- 12050529
TI  - Polyorchidism: a strange anomaly with unsuspected properties.

PMID- 12050531
TI  - Re: Antitumor effects of the intravesical instillation of heat killed cells of
      the Lactobacillus casei strain shirota on the murine orthotopic bladder tumor MBT
      2.

PMID- 12050532
TI  - Re: Prospective evaluation of prostate cancer detected on biopsies 1, 2, 3 and 4:
      when should we stop?

PMID- 12050534
TI  - Re: Diethylstilbesterol revisited: androgen deprivation, osteoporosis an prostate
      cancer.

PMID- 12050535
TI  - Re: Optimal prevention and management of proximal ureteral stent migration and
      remigration.

PMID- 12050537
TI  - Re: Buccal mucosal grafts: lessons learned from an 8-year experience.

PMID- 12050538
TI  - Re: Treatment of incontinence in children with bladder exstrophy after rectal
      urinary diversion: the anal sling procedure.

PMID- 12050539
TI  - Re: 25-year experience with replacement of the human bladder (Camey procedure).

PMID- 12050540
TI  - Re: Life after radical prostatectomy: a longitudinal study.

PMID- 12050541
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12050542
TI  - Tachyphylaxis and phosphodiesterase type 5 inhibitors.

PMID- 12050543
TI  - Plastic repair of exstrophy of bladder combined with bilateral osteotomy of ilia.
      1958.

PMID- 12050544
TI  - Surgical treatment of exstrophy of the bladder with emphasis on neonatal primary
      closure: personal experience with 28 consecutive cases treated at the University
      of Washington Hospitals from 1962 to 1977: techniques and results. 1979.

PMID- 12050546
TI  - Lymphangioma of the renal capsule.

PMID- 12050547
TI  - Laparoscopic adrenal surgery in children.
AB  - PURPOSE: The laparoscopic approach to the adrenal gland was first reported in
      1992. Since then, more than 400 studies have been published, comprising hundreds
      of adults. There are few reports of laparoscopic adrenalectomy in the pediatric
      population. We reviewed our experience with laparoscopic adrenal surgery in
      children. MATERIALS AND METHODS: Laparoscopic adrenalectomy was performed in 8
      girls and 5 boys 15 years or younger (mean age 6.3) between December 1994 and
      August 2001. The clinical diagnosis before surgery was virilizing tumor in 5
      cases, nonfunctioning solid adrenal tumor in 3, Cushing's syndrome in 2,
      pheochromocytoma in 2 and Cushing's pituitary disease in 1. Unilateral adrenal
      lesions were 15 to 80 mm. at the longest axis (mean 41.4) on computerized
      tomography. RESULTS: Two of the 13 procedures (15.4%) were converted to open
      surgery. No deaths occurred. No patients presented with postoperative
      complications. Average operative time in unilateral nonconverted procedures was
      107 minutes (range 25 to 195). Blood transfusion was required in 1 case (7.7%).
      Average hospital stay was 5.5 days (range 1 to 17). Average postoperative
      followup was 16 months (range 1 to 60). The final clinicopathological diagnosis
      was virilization in 4 cases, Cushing's syndrome in 2, pheochromocytoma in 2,
      neuroblastoma in 2, Cushing's pituitary disease in 1, teratoma in 1 and primary
      carcinoma in 1. CONCLUSIONS: Laparoscopic adrenalectomy is feasible and shows
      positive results in select pediatric patients.

PMID- 12050548
TI  - Follicular large cell lymphoma localized to the testis in children.
AB  - PURPOSE: Primary follicular lymphoma of the testis in childhood is rare with only
      6 cases previously reported. We present 3 additional cases. MATERIALS AND
      METHODS: We extensively analyzed primary follicular lymphoma of the testis in 3
      boys. Clinical data were obtained by reviewing patient charts. RESULTS: The
      patients were 4, 5 and 11 years old, respectively. Two patients presented with
      painless unilateral testicular enlargement and 1 presented with unilateral
      hydrocele. Laboratory findings were within normal limits in all patients. Radical
      orchiectomy was done in all cases. The excised testes were partially or
      completely replaced by tumor. In all cases the features were those of follicular,
      large cell-type malignant lymphoma. Tumor cells in all cases were CD20 and CDw75
      positive, focally CD23 positive and bcl-2 negative, while in 2 they were CD10
      positive and bcl-6 positive. Surface Ig was absent in the 2 cases studied.
      Karyotyping in 1 case showed a normal karyotype. Staging revealed no evidence of
      extratesticular disease. All patients underwent combination chemotherapy and were
      in complete remission 7 to 59 months after therapy. CONCLUSIONS: We present 3
      cases of pediatric primary follicular lymphoma of the testis. Pathological
      findings and clinical features were similar to those in the 6 previously reported
      cases and suggest that primary pediatric testicular follicular lymphoma may
      represent unique subset of follicular lymphoma with a particularly good
      prognosis.

PMID- 12050549
TI  - Developmental anomalies and disabilities associated with hypospadias.
AB  - PURPOSE: The incidence of developmental anomalies and disabilities associated
      with hypospadias is still a matter of controversy and data on this issue are
      sparse. We describe our experience with and evaluation of developmental anomalies
      and disabilities in a population in which posterior hypospadias was the most
      common anomaly. MATERIALS AND METHODS: We reviewed the records of 356 patients
      who underwent hypospadias repair from January 1986 through April 2000. Collected
      data included the Barcat classification of the hypospadias anomaly, anatomical
      penile variants, associated urogenital and extra-urogenital anomalies, and
      associated disabilities of physical and mental development. RESULTS: Of the 356
      patients 234 (65.7%) had posterior, 88 (24.7%) anterior and 34 (9.6%) mid
      hypospadias. Anatomical variants, including penoscrotal transposition, bifid
      scrotum and micropenis, occurred predominantly in patients with posterior
      hypospadias, while penile torsion was present exclusively in the other 2 groups.
      Inguinal hernia, which was the most common urogenital anomaly, was distributed
      evenly among the 3 groups with a prevalence rate of 12.4%. Undescended testis in
      26 cases (7.3%) was most often associated with posterior hypospadias. In order of
      frequency associated extra-urogenital anomalies included congenital heart disease
      in 19 cases (5.3%), musculoskeletal anomalies in 11 (3.1%), anorectal
      malformation in 6 (1.7%), cleft palate in 3 and other in 7. In 21 patients (5.9%)
      associated disorders were related to physical and mental development, including
      growth retardation in 6, cerebral palsy in 2 and psychological disorders that
      significantly impaired patient bodily function, behavior and performance in 11.
      Most extra-urogenital anomalies or disorders were associated with posterior
      hypospadias. CONCLUSIONS: Posterior hypospadias was the most common anomaly in
      this study. It was associated with a high rate of extra urogenital anomalies, and
      physical and psychosocial disabilities. The significance of the latter findings
      with respect to the development of affected patients needs further clarification.

PMID- 12050550
TI  - Antisense oligonucleotide therapy in urology.
AB  - PURPOSE: Antisense oligonucleotides are short modified DNA or RNA molecules
      designed to bind selectively messenger RNA and inhibit synthesis of the encoded
      protein. In the last 20 years antisense technology has emerged as an exciting and
      promising strategy, especially for treating cancer. We provide urologists with a
      contemporary review of relevant background information and outline current
      treatment strategies and clinical trials of antisense oligonucleotide therapy for
      urological tumors. MATERIALS AND METHODS: We comprehensively reviewed the
      literature, including PubMed and recent abstract proceedings from international
      meetings, on preclinical and clinical studies of antisense oligonucleotide
      therapy in urology. RESULTS: Current preclinical antisense strategies in
      urological cancer research include the inhibition of proliferation and induction
      of tumor cell differentiation, reversal of immunosuppression by tumor secreted
      molecules and induction of apoptosis. The use of phosphorothioate
      oligonucleotides as antisense agents has shown promising results in various
      preclinical cancer models. In recent and current clinical trials in patients with
      urological tumors antisense agents targeted against c-raf kinase, protein kinase
      C-alpha, protein kinase A and bcl-2 are being evaluated. CONCLUSIONS: Many
      compounds have achieved convincing in vitro reduction of target messengerRNA and
      protein expression. Early clinical trials show safety and mild toxicity at the
      given doses. Overall the current state of antisense oligonucleotide research
      described promises a highly productive future for this technology. However, for
      most medical applications of antisense compounds many obstacles related to
      nuclease stability, affinity, cellular delivery and specificity remain to be
      clarified.

PMID- 12050551
TI  - Simulated ischemia induces renal tubular cell apoptosis through a nuclear factor
      kappaB dependent mechanism.
AB  - PURPOSE: Ischemia-reperfusion injury is a relatively common cause of renal
      tubular cell death and acute renal failure. While nuclear factor-kappaB has been
      implicated in the pathophysiology of renal ischemia-reperfusion injury, the
      effect of nuclear factor-kappaB inhibition on ischemia induced renal tubular cell
      death remains unknown. MATERIALS AND METHODS: Renal tubular cells (LLC-PK1) were
      exposed to simulated ischemia in the presence or absence of 10 microM.
      pyrrolidine dithiocarbamate (nuclear factor-kappaB inhibitor). Nuclear factor
      kappaB activation (electrophoretic mobility shift assay and immunohistochemistry)
      and the effect of pyrrolidine dithiocarbamate on nuclear factor-kappaB activation
      (electrophoretic mobility shift assay) and ischemia induced apoptosis (terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling) were determined. RESULTS: Simulated ischemia induced nuclear factor
      kappaB activation and renal tubular cell apoptosis versus controls (mean plus or
      minus standard error of mean 62 +/- 5.2 versus 0.4 +/- 0.3 apoptotic nuclei per
      high power field, p <0.05). In contrast, previous cellular exposure to
      pyrrolidine dithiocarbamate effectively inhibited nuclear factor-kappaB
      activation and prevented ischemia induced apoptosis (mean 14 +/- 6 apoptotic
      nuclei per high power field). CONCLUSIONS: Simulated ischemia induces nuclear
      factor-kappaB intranuclear translocation and activation in renal tubular cells.
      Furthermore, nuclear factor-kappaB mediates ischemia induced renal tubular cell
      apoptosis. Further elucidation of the complex role of nuclear factor-kappaB in
      inflammatory injury may lead to the development of targeted therapeutic
      strategies that ameliorate ischemic renal injury.

PMID- 12050552
TI  - Effects of oxalate on HK-2 cells, a line of proximal tubular epithelial cells
      from normal human kidney.
AB  - PURPOSE: Oxalate, a metabolic end product, is a major constituent of majority of
      renal stones. Previous studies with LLC-PK1 cells, a line of proximal renal
      epithelial cells of porcine origin, have shown that oxalate produces time and
      concentration dependent effects on the growth and viability of these cells. We
      assessed the possibility that oxalate may be toxic to HK-2 cells, a line of human
      proximal renal epithelial cells. MATERIALS AND METHODS: HK-2 cells were
      maintained in Dulbecco's modified Eagle's medium supplemented with fetal bovine
      serum and antibiotics. Cells were exposed to oxalate for various intervals.
      Trypan blue exclusion criteria were used to assess membrane integrity, cell
      morphology was assessed by hematoxylin and eosin staining and crystal violet
      staining was used to measure cell density. DNA synthesis was measured by [3H]
      thymidine incorporation and superoxide production was measured by the nitroblue
      tetrazolium reduction method. RESULTS: Exposure of HK-2 cells to oxalate produced
      time and concentration dependent increase in the membrane permeability to trypan
      blue and changes in the light microscopic appearance of the cells. Long-term
      exposure to oxalate resulted in an increase in DNA synthesis and alterations in
      cell viability with net cell loss after exposure to high oxalate concentrations.
      CONCLUSIONS: To our knowledge the results provide the first direct demonstration
      of the toxic effects of oxalate in HK-2 cells, a line of human renal epithelial
      cells, and suggest that hyperoxaluria may contribute to renal tubular damage
      associated with calcium oxalate stone disease.

PMID- 12050553
TI  - Predicting urinary stone composition using X-ray coherent scatter: a novel
      technique with potential clinical applications.
AB  - PURPOSE: Coherent scatter properties depend on the molecular structure of the
      scattering medium and measured scatter patterns are often characteristic of a
      chemical species. We explored the usefulness of coherent scatter analysis as a
      basis for identifying urinary calculus composition. MATERIALS AND METHODS: A
      laboratory system for collecting coherent scatter signals from biological
      specimens was developed. This technique uses a diagnostic x-ray tube and image
      intensifier, and measures coherent scatter from intact renal stones. The coherent
      scatter signatures of 6 common stone components (calcium oxalate monohydrate,
      calcium phosphate, calcium phosphate dihydrate, cystine, magnesium ammonium
      phosphate and uric acid) were acquired from pure chemical samples and stones
      identified by infrared spectroscopy as having a uniform composition. In addition,
      a sample of calculus identified as containing only calcium oxalate dihydrate was
      examined. The same fragmented stone samples analyzed by infrared spectroscopy
      were scanned using coherent scatter. RESULTS: In each case the scatter patterns
      from powdered chemicals and fragmented stones showed circular symmetry and
      consisted of a series of broad rings of various intensities. Each pure chemical
      sample produced a distinct coherent scatter pattern. The signatures of the stone
      specimens closely agreed with those of the chemical samples. CONCLUSIONS: These
      initial results indicate that coherent scatter analysis using diagnostic x-rays
      has potential as a tool for urinary calculous composition identification. Further
      developments in this technique may have the potential for determining the
      composition of a calculus in vivo before therapy, thus, aiding in therapy
      planning.

PMID- 12050554
TI  - Epidermal growth factor receptor targeting of replication competent adenovirus
      enhances cytotoxicity in bladder cancer.
AB  - PURPOSE: We evaluated the delivery and oncolytic potential of targeted
      replication competent adenoviruses in bladder cancer lines. MATERIALS AND
      METHODS: Seven established human bladder cancer tumor lines (5637, SW800, TCCsup,
      J82, Scaber, T24 and 253J) were studied for the expression of integrins
      alpha(v)beta3, alpha(v)beta5, Coxsackievirus and adenovirus receptor, epidermal
      growth factor receptor (EGF-R) and epithelial cell adhesion molecule antigens
      using flow cytometry analysis. Bispecific single chain Fv fragments were used to
      target replication deficient luciferase reporter adenovirus to EGF-R (425-s11) or
      to epithelial cell adhesion molecule (C28-s11) antigens. Moreover, a fiber
      modified adenovirus targeting alpha(v)-integrins was studied. Replication
      competent serotype-5 adenoviruses attenuated to replicate specifically in
      retinoblastoma pRb (Ad5-d24) or p53 deficient (Ad5-d55K) cells were tested in
      vitro for oncolytic properties. RESULTS: Low to absent Coxsackievirus and
      adenovirus receptor expression was found in 5 of the 7 tumor lines (SW800, J82,
      T24, 5637 and Scaber). EGF-R expression was found in all cell lines, whereas
      elevated epithelial cell adhesion molecule expression was seen in 3 (5637, Scaber
      and TCCsup), alpha(v)beta3-integrin was found in 1 (Scaber) and alpha(v)beta5
      integrin was found in 3 (TCCsup, 253J and T24). EGF-R targeting using 425-s11
      improved transgene expression in all cell lines from 2.1 to 12.5 times over
      nontargeted viruses. Epithelial cell adhesion molecule and integrin targeting was
      inferior to EGF-R targeting with a maximal increase in transgene expression of 2
      times for epithelial cell adhesion molecule in 5637cells and 1.6 times for
      integrin targeting in T24 cells. Comparison of the wild-type replication
      competent virus with conditionally replicating adenoviruses (Ad5-d55K and Ad5
      d24) showed superior oncolytic activity for the latter 2 in all lines.
      Furthermore, improved cytotoxicity (29% to 33%) was obtained in 4 of the 7 lines
      after pre-incubation of Ad5-d24 with 425-s11. CONCLUSIONS: EGF-R directed
      bispecific single chain antibodies enhance adenovirus mediated transgene
      expression and oncolysis in bladder cancer lines.

PMID- 12050555
TI  - Comparison of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for positron
      emission tomography of androgen dependent and androgen independent prostate
      cancer.
AB  - PURPOSE: Positron emission tomography (PET) imaging is used for the metabolic
      evaluation of cancer. [18F]fluorodeoxyglucose (FDG) is commonly used as a
      radiotracer but its low cellular uptake rate in prostate cancer limits its
      usefulness. We evaluated the novel choline analog [18F]fluorocholine (FCH) for
      detecting androgen dependent and androgen independent prostate cancer, and its
      metastases. MATERIALS AND METHODS: The cellular uptake of FCH and FDG was
      compared in cultured prostate cancer cells (LNCaP and PC-3). FCH and FDG were
      injected into nude mice xenografts (CWR-22 and PC-3) and radiotracer uptake in
      various organs were evaluated. Patients with androgen dependent (9) and
      independent (9) prostate cancer were studied by FCH and FDG PET. RESULTS: FCH
      uptake was 849% and 60% greater than FDG uptake in androgen dependent (LNCaP) and
      independent (PC-3) cells, respectively. The addition of hemicholinium-3 (5 mM.)
      30 minutes before radiotracer administration inhibited FCH uptake by 79% and 70%
      in LNCaP and PC-3 cells, respectively, whereas FDG uptake was not significantly
      affected. Although nude mice xenografts showed that FDG uptake was equal to or
      greater than FCH uptake, clinical imaging in patients demonstrated 2 to 4-fold
      higher uptake of FCH in those with androgen and androgen independent prostate
      carcinoma (p <0.001). More lesions were detected by FCH than by FDG in primary
      tumors, osseous metastases and soft tissue metastases. CONCLUSIONS: In vitro data
      demonstrated greater FCH than FDG uptake in androgen dependent (LNCaP) and
      androgen independent (PC-3) prostate cancer cells. Although the murine xenograft
      data showed greater accumulation of FDG than FCH in PC-3 tumors, PET in humans
      showed that FCH was better than FDG for detecting primary and metastatic prostate
      cancer. Overall the data from this study suggest that FCH is preferable to FDG
      for PET of prostate carcinoma and support the need for future validation studies
      in a larger number of subjects.

PMID- 12050556
TI  - Laser welded vesicourethral anastomosis in an in vivo canine model: a pilot
      study.
AB  - PURPOSE: We evaluated laser welding as an alternative method of forming the
      vesicourethral anastomosis. MATERIALS AND METHODS: Eight dogs underwent open
      total prostatectomy, including 4 in which the vesicourethral anastomosis was
      formed by 830 nm. diode laser welding using a chromophore doped albumin solder
      and 3 or 4 support sutures. The remaining 4 anastomoses were conventionally
      formed using 8 interrupted sutures. Acute leakage was tested intraoperatively.
      The anastomosis of 1 animal per group was assessed on postoperative days 3, 5, 7
      and 14 by radiography before sacrifice. Each anastomotic specimen was then tested
      for leak pressure and examined histologically. RESULTS: There were no leaks
      during intraoperative testing of laser welded or sutured anastomoses. On
      radiography there were no leaks in the laser welded group. In 1 control there was
      slight localized leakage. All anastomoses achieved physiological leak pressures
      of 70 mm. Hg or greater with 3 of the 4 in the laser welded group recording
      supraphysiological pressures of greater than 200 mm. Hg. While 3 of the 4 laser
      welded specimens showed evidence of muscle necrosis, there were no other
      differences in healing in the 2 groups. CONCLUSIONS: These short-term results
      suggest that diode laser welded vesicourethral anastomosis is feasible. This
      technique has the potential to simplify anastomotic formation in laparoscopic
      radical prostatectomy, shortening operative time. Diode laser welding in this
      small cohort created an immediate and ongoing watertight anastomosis and,
      therefore, it may also be an alternative in open radical prostatectomy cases.
      Further study is needed to assess long-term effects on healing.

PMID- 12050557
TI  - De-serosalized muscle layer covering method for antireflux ureteroileostomy: a
      new operative technique and pressure study with ureterometry at the ureteroileal
      anastomotic site in dogs.
AB  - PURPOSE: In pursuit of a more effective antireflux ureteroileostomy with a lower
      postoperative complication rate we performed a new operative technique and
      evaluated intraureteral pressure with ureterometry to examine the mechanism of
      antireflux function. MATERIALS AND METHODS: A total of 11 beagle dogs were used
      in this study. A 3 x 2 cm. section of the ileal serosa was removed, the severed
      ureter was directly anastomosed to the de-serosalized area and 1 cm. of terminal
      ureter and the direct anastomotic site were covered with the de-serosalized ileal
      wall. The bladder was augmented with the ileum containing the ureter.
      Postoperative evaluations were performed monthly and ureterometry of the
      reimplanted ureter was done 6 months postoperatively. RESULTS: Complete reflux
      prevention and a low stricture rate were achieved with this procedure. Direct
      ureteroileal anastomosis caused stricture in 1 of the 11 ureters but the covering
      procedure to prevent ureteral reflux caused no ureteral strictures. When the
      bladder was empty, ureteral closure pressure at the intramural portion of the
      ureter was low. At the phase of high intravesical pressure ureteral closure
      pressure at the intramural ureter was as high as intravesical pressure.
      CONCLUSIONS: The de-serosalized muscle layer covering method prevented ureteral
      reflux completely with a low stricture rate. The antireflux function of this
      method seems to depend on the flexibility of the terminal ureter covered with the
      de-serosalized ileal wall. Reflux prevention in the low intravesical pressure
      phase seems to be due to extension of the ileal wall.

PMID- 12050558
TI  - Sodium pentosan polysulfate reduces urothelial responses to inflammatory stimuli
      via an indirect mechanism.
AB  - PURPOSE: Sodium pentosan polysulfate has been promoted as a urothelial
      cytoprotective agent for treating interstitial cystitis. The nuclear
      transcription factor nuclear factor kappaB is thought to have a role in mediating
      the urothelial inflammatory response of interstitial cystitis. We further defined
      a possible cytoprotective effect of sodium pentosan polysulfate by characterizing
      the effect of the drug on the expression of nuclear factor kappaB. MATERIALS AND
      METHODS: For cell culture human urothelial cells were incubated in various
      concentrations of sodium pentosan polysulfate for 16 hours in keratinocyte serum
      free medium. They were subsequently treated with the known nuclear factor kappaB
      stimulants tumor necrosis factor-alpha, lipopolysaccaride (LPS) and double
      stranded RNA (dsRNA). Each stimulant was then incubated with sodium pentosan
      polysulfate separately and the mixture was used to treat cultured urothelial
      cells. For electrophoretic mobility shift assay total cell extracts were prepared
      and run in electrophoretic mobility shift assays using a radiolabeled nuclear
      factor kappaB consensus sequence as a probe. Western blot analysis was done to
      assess nuclear factor kappaB activation by measuring degradation of the
      inhibitory subunit of the nuclear factor kappaB complex. RESULTS: Nuclear factor
      kappaB activation by tumor necrosis factor-alpha, LPS and dsRNA was unaltered
      when cultured cells were incubated in sodium pentosan polysulfate before
      treatment. In contrast, nuclear factor kappaB activation by LPS and dsRNA was
      suppressed when the stimulants were incubated with sodium pentosan polysulfate
      before cell treatment. This suppressive effect was confirmed by Western blot
      analysis. CONCLUSION: Sodium pentosan polysulfate may have a nonspecific effect
      against the viral (dsRNA) and bacterial (LPS) activation of nuclear factor
      kappaB. The observed clinical effect of sodium pentosan polysulfate may be
      mediated by nonspecific binding of sodium pentosan polysulfate molecules and the
      inflammatory stimulants of urothelial activation. These findings suggest a
      mechanism of action for sodium pentosan polysulfate that occurs in the urine
      rather than at the mucosal membrane by direct interaction of the drug with
      potential interstitial cystitis inducing inflammatory agents.

PMID- 12050559
TI  - Topography of the vanilloid receptor in the human bladder: more than just the
      nerve fibers.
AB  - PURPOSE: We determined the presence and distribution of vanilloid receptor-1 in
      the human bladder and confirmed or rejected previous findings of other groups
      that used indirect methods or vanilloid receptor-1 antibodies made by immunizing
      experimental animals. Also, we tested the reproducibility of results using
      commercially available antibodies against the N-terminus and C-terminus of the
      vanilloid receptor. MATERIALS AND METHODS: A total of 11 normal bladder tissue
      samples were obtained from cystectomy specimens and fresh frozen processed.
      Specimens were studied by immunohistochemistry and confocal laser microscopy
      using 3 vanilloid receptor-1 antibodies. Immunohistochemical co-localization
      studies for neurofilament, neuronal nitric oxide synthase and nerve growth factor
      were performed. RESULTS: Our results confirm the presence of vanilloid receptor-1
      on nonmyelinated and myelinated nerve fibers. There was vanilloid receptor-1
      immunoreactivity on smooth muscle cells but different sensitivities for the
      antibodies. There was immunoreactivity on interstitial cells located in the
      suburothelium and intermuscular septa of the muscularis. There was co
      localization of neuronal nitric oxide synthase with interstitial cells but not
      with neurofilament. No co-localization was found for nerve growth factor and
      vanilloid receptor-1. CONCLUSIONS: Vanilloid receptor-1 is located on small
      unmyelinated and myelinated nerve fibers. In addition, vanilloid receptor-1 is
      also present on interstitial cells in the suburothelium. There is smooth muscle
      cell immunoreactivity but a difference in antibodies raised against the C
      terminus and N-terminus. These data suggest that the current hypothesis about the
      mechanism of action of vanilloids is through blocking the afferent reflex arc
      must be revised and the function of interstitial cells deserves further
      attention.

PMID- 12050560
TI  - Infravesical obstruction in aromatase over expressing transgenic male mice with
      increased ratio of serum estrogen-to-androgen concentration.
AB  - PURPOSE: The potential role of estrogen in the development of infravesical
      obstruction is still unresolved. Aromatase over expressing transgenic mice
      provide a novel instrument for investigating the consequences of prolonged
      systemic or local increases in endogenous estrogen concentrations. Two aromatase
      over expressing transgenic mouse strains with different prostatic phenotypes
      (reduced and normal size, respectively) were compared in urodynamic studies with
      each other and with the wild-type strain. MATERIALS AND METHODS: The bladder and
      urethra were exposed in adult male wild-type or transgenic mice. High frequency
      oscillations of intraluminal bladder pressure and flow rate from the distal
      urethra were simultaneously recorded with the mice under anesthesia. RESULTS: No
      changes were observed in voiding in MMTV-arom+ mice. These mice are known to have
      only slightly elevated estradiol concentrations in serum, suggesting a localized
      increase in estrogen production. In AROM+ mice the aromatase gene was detected in
      several organs, including the testis and bladder. These mice are known to have
      markedly increased estrogen and decreased serum androgen concentrations, and
      reduced prostate size. Compared with wild-type mice AROM+ mice showed higher mean
      maximal bladder pressure plus or minus standard deviation (33.1 +/- 6.4 versus
      25.6 +/- 4.8 mm. Hg, p = 0.046) and decreased mean maximal flow rate (3.1 +/- 1.6
      versus 17.7 +/- 5.4 ml. per minute, p <0.0001), consistent with the presence of
      the infravesical obstruction. Morphologically the proximal rhabdosphincter in
      AROM+ mice showed atrophy (relative mean thickness 0.005 +/- 0.015 versus 0.013
      +/- 0.002 mm., p <0.0001). CONCLUSIONS: Activation of the aromatase gene during
      an earlier developmental stage under the ubiquitin C promoter and highly elevated
      serum estrogen concentrations may explain the differences in voiding and prostate
      size in the AROM+ mouse strain.

PMID- 12050561
TI  - Changed responsiveness of the detrusor in rabbits with alloxan induced
      hyperglycemia: possible role of 5-hydroxytryptamine for diabetic bladder
      dysfunction.
AB  - PURPOSE: We assessed whether the responsiveness of the detrusor is changed in
      rabbits with alloxan induced hyperglycemia. MATERIALS AND METHODS: Hyperglycemia
      was induced by a bolus intravenous injection of alloxan (60 mg./kg.) in Japanese
      White male rabbits. At 16 weeks after alloxan detrusor muscle strips prepared
      from age matched normoglycemic and hyperglycemic rabbits were mounted in organ
      chambers. Contractile responses to KCl, carbachol, adenosine triphosphate, 5
      hydroxytryptamine and electrical field stimulation were compared in the 2 groups.
      The effect of sarpogrelate as a selective antagonist of 5-hydroxytryptamine 2A
      receptor on the contractile response to 5-hydroxytryptamine was also compared.
      RESULTS: The current experiments demonstrated that hyperglycemia caused
      significant decreases in neurogenic and carbachol induced contractions
      accompanied by unchanged adenosine triphosphate and KCl induced contractions.
      Neurogenic bladder contraction in the hyperglycemic rabbit was significantly
      potentiated by exogenously applied 5-hydroxytryptamine. Potentiation was
      detectable even after the desensitization of purinoceptors but undetectable in
      the presence of atropine. Hyperglycemia resulted in enhancement of the 5
      hydroxytryptamine induced bladder contraction. Sarpogrelate tended to normalize
      the enhanced contraction. CONCLUSIONS: The decrease in neurogenic bladder
      contraction possibly accompanied by the decreased density of muscarinic
      receptors, the potentiation of neurogenic bladder contraction with 5
      hydroxytryptamine probably due to facilitated cholinergic transmission and the
      enhanced contractility to 5-hydroxytryptamine would be at least in part involved
      in bladder dysfunction associated with hyperglycemia.

PMID- 12050562
TI  - The role of M2 muscarinic receptor subtypes mediating contraction of the circular
      and longitudinal smooth muscle of the pig proximal urethra.
AB  - PURPOSE: We investigated the characterization of muscarinic receptor subtypes in
      the female pig urethra. MATERIALS AND METHODS: The affinities of muscarinic
      antagonists against carbachol responses were calculated in normal and cyclic
      adenosine monophosphate (cAMP) elevated tissues (contraction with KCl and
      relaxation with isoprenaline) using longitudinal and transverse strips of
      urethra. RESULTS: In displacement experiments with 1-quinuclidinyl [phenyl-4-3H]
      benzilate inhibitory constant (pKi) values of 4-diphenylacetoxyl-N-methyl
      piperidine methiodide (DAMP) M3 selective antagonist) and methoctramine (M2
      antagonist) indicated the presence of the M2 receptor. In functional studies
      contraction responses to carbachol were greater in longitudinal than in circular
      muscle. After cAMP elevation the contraction response increased in circular
      muscles to the level close to that of longitudinal muscles but did not change
      significantly in cAMP elevated longitudinal muscle. On normal circular tissues 4
      DAMP had high mean affinity (mean apparent pKB value 9.3) but with a Schild slope
      of less than unity (0.76). Methoctramine competitively antagonized carbachol
      responses (mean affinity [pA2] value 6.9). On normal longitudinal tissues 4-DAMP
      and methoctramine competitively antagonized carbachol responses (mean pA2 9.0 and
      6.2, respectively). After cAMP elevation in circular tissues mean pA2 values for
      4-DAMP (8.7) were significantly lower (p = 0.0015), and those for methoctramine
      (7.3) were significantly higher (p = 0.0193) than in normal tissues. In
      longitudinal tissues the mean pA2 value for methoctramine (6.9) was significantly
      greater than in normal tissues (p <0.0001) but the value for 4-DAMP (8.8) did not
      alter. CONCLUSIONS: Pig urethra appears to have predominantly M2 muscarinic
      receptors. Contraction of the normal urethra appears to be predominantly mediated
      by M2 and M3 receptors in circular muscle but by M3 receptors in longitudinal
      muscle. After cAMP elevation a contribution to contraction of M2 receptors
      appeared to be demonstrated in the 2 tissues but the involvement of M2 receptors
      appeared greater in circular muscle.

PMID- 12050563
TI  - Spontaneous slow wave and contractile activity of the guinea pig prostate.
AB  - PURPOSE: We characterized the electrical events underlying spontaneous
      contractions of the stroma of the guinea pig prostate. MATERIALS AND METHODS:
      Membrane potential of the stroma was recorded using standard electrophysiological
      recording techniques. The structure of the prostate was viewed using confocal or
      electron microscopy. RESULTS: In stromal cells spontaneous depolarizing membrane
      transients (12 mV. in amplitude) occurred at 5 minutes-1 and triggered 1 or more
      spikes. The membrane potential, and frequency and duration of the potential
      transients were not affected by the calcium channel blocker nifedipine (1 microM.
      for greater than 5 minutes), or blockers of neuronal propagation (tetrodotoxin),
      and the effects of cholinergic (atropine), adrenergic (guanethidine or prazosin)
      and sensory blockers (capsaicin) of neurotransmission. However, the amplitude of
      the superimposed spikes was significantly reduced by nifedipine. A network of c
      Kit immunoreactive cells was evident in the interstitial layer between the stroma
      and glandular lined lumen. These prostatic interstitial cells contained many
      morphological features distinguishing interstitial cells of Cajal, the pacemaker
      cells of the gastrointestinal tract. Prostatic interstitial cells formed close
      appositions with each other, with neighboring smooth muscle cells and with
      varicose axon bundles. CONCLUSIONS: Movement of the contents of the peripheral
      prostatic acini into the minor and major prostatic ducts is likely to occur via
      spontaneous contractions triggered by myogenic slow wave activity in the stromal
      wall. By analogy with the intestine and urethra prostatic interstitial cells may
      well act as the pacemaker for prostatic slow waves as well as form an
      intercellular communication network interacting with the intrinsic nerves and
      stromal cells.

PMID- 12050564
TI  - Long-term effect of ovariectomy and simulated birth trauma on the lower urinary
      tract of female rats.
AB  - PURPOSE: Using an animal model we studied the long-term effects of ovariectomy
      and simulated birth trauma in the development of apoptosis as well as the
      urodynamic, histological and ultrastructural findings 9 months after such
      procedures. MATERIALS AND METHODS: A total of 24 pregnant Sprague-Dawley female
      rats were used. Immediately after delivery 14 animals underwent vaginal
      ballooning and ovariectomy, while the remaining 10 served as controls. At 9
      months the animals underwent urodynamic evaluation, which included the urethral
      pressure profile. The rats were then sacrificed and urogenital tissue was
      obtained for immunostaining using terminal deoxynucleotidyl transferase mediated
      deoxyuridine triphosphate nick end-labeling, histomorphometry evaluation and
      electron microscopy. RESULTS: Immunostaining demonstrated a significant increase
      in the apoptotic index in the urethra of castrated/ballooning rats with a
      predominance in the submucosa layer. Maximum urethral closure pressure was
      significantly lower in that group, although there was no correlation of apoptosis
      with maximum urethral closure pressure measurement. Urodynamic evaluation
      revealed only discrete alterations in cystometric parameters. Morphometric
      evaluation showed increased connective tissue in the vagina. Electron microscopy
      of urethral smooth muscle demonstrated altered cellular shape, increased
      intercellular space with collagen deposition and some degeneration of the
      mitochondria. CONCLUSIONS: Apoptosis in the urethra occurs 9 months after
      castration and simulated birth trauma. However, this finding was not seen in the
      muscle layers or in other urogenital tissues. Some ultrastructural changes also
      occurred that may explain some symptoms that women have after vaginal childbirth
      and menopause.

PMID- 12050565
TI  - Cytokine polymorphisms in men with chronic prostatitis/chronic pelvic pain
      syndrome: association with diagnosis and treatment response.
AB  - PURPOSE: The chronic pelvic pain syndrome is a common disorder of unknown
      etiology. Elevated cytokines in prostate fluid and semen are frequent findings.
      We studied genetic polymorphisms that can alter cytokine gene expression in men
      with the chronic pelvic pain syndrome. MATERIALS AND METHODS: Genomic DNA was
      extracted from blood from 36 men with the chronic pelvic pain syndrome. Reversed
      sequence specific oligonucleotide probing was used to genotype the polymorphisms
      for cytokine promoter sites, namely tumor necrosis factor (TNF)-alpha 308,
      transforming growth factor (TGF)-beta 25, TGF-beta 10, interleukin (IL)-10 1082
      and IL-6 174. Genotype frequencies were compared with 252 controls as well as
      among groups of patients with the chronic pelvic pain syndrome according to
      diagnostic category and treatment response. RESULTS: There were no differences in
      men with the chronic pelvic pain syndrome and control patients in the frequency
      of TNF-alpha, TGF-beta or IL-6 alleles, although those with the chronic pelvic
      pain syndrome were more likely to express the genotype associated with low IL-10
      production (30.6% versus 12.1%, p = 0.007). When comparing National Institutes of
      Health diagnoses, category IIIa patients were more likely to have the low TNF
      alpha genotype (categories II, IIIa and IIIb 33%, 100% and 18%, respectively, p =
      0.04). All 11 of the 28 patients treated with the anti-inflammatory quercetin in
      whom treatment failed had the low TNF-alpha genotype versus 29.4% of those in
      whom treatment succeeded (p = 0.0003). Similarly men with quercetin treatment
      failure were much less likely to have the low IL-10 genotype than those with
      treatment success (9.1% versus 47.1%, p = 0.04). CONCLUSIONS: Patients with the
      chronic pelvic pain syndrome are more likely to have a low IL-10 producing
      genotype, suggesting autoimmunity as a potential etiology. Anti-inflammatory
      phytotherapy failure was associated with low TNF-alpha and high IL-10 phenotypes,
      which may help define a subset of patients with the chronic pelvic pain syndrome
      without an inflammatory etiology.

PMID- 12050566
TI  - Expression, localization and activity of neutral endopeptidase in cultured cells
      of benign prostatic hyperplasia and prostate cancer.
AB  - PURPOSE: Neutral endopeptidase is a cell surface enzyme that cleaves and
      inactivates neuropeptides. Neutral endopeptidase is expressed by prostatic
      epithelial cells and is thought to have a key role in the growth of androgen
      independent prostate cancer. In contrast to the encouraging data dealing with
      neutral endopeptidase and prostate cancer progression, only few studies are
      available of the significance of neutral endopeptidase in prostatic stromal cells
      and benign prostatic hyperplasia (BPH). We report the expression and activity of
      neutral endopeptidase in human prostatic stromal cells. MATERIALS AND METHODS: We
      recently established and characterized human prostatic stromal cells from BPH
      tissue. Reverse transcriptase-polymerase chain reaction, Western blot experiments
      and immunohistochemistry were performed to investigate the expression levels of
      neutral endopeptidase and show the cellular localization of the enzyme in these
      cells. Enzymatic neutral endopeptidase activity was evaluated using a
      colorimetric assay in nonstimulated cells, and after androgen and estrogen
      application. RESULTS: Stromal BPH cells showed strong expression of the neutral
      endopeptidase messenger RNA and protein, equaling the neutral endopeptidase
      expression level in prostate cancer cells. The neutral endopeptidase protein
      located in the plasma membrane of the cells showed a mean enzymatic activity plus
      or minus standard deviation of 75% +/- 2.5% compared with LNCaP prostate cancer
      cells. Interestingly enzymatic activity of the membrane bound neutral
      endopeptidase in stromal cells was not regulated by androgen and estrogen.
      CONCLUSIONS: These data suggest that neutral endopeptidase is expressed by
      prostatic stromal cells. In addition to its role in the progression of prostate
      cancer, it may also be involved in regulatory processes in the stroma, namely the
      degradation of neuropeptides released from prostatic neuroendocrine cells.

PMID- 12050567
TI  - Germ cell apoptosis in undescended testis: the origin of its impaired
      spermatogenesis in the TS inbred rat.
AB  - PURPOSE: Undescended testis is one of the most important congenital anomalies in
      male urogenital organs that may cause male infertility. We examined the process
      of spermatogenesis of TS inbred rats, of which approximately 70% of male newborns
      have congenital undescended testes. MATERIALS AND METHODS: Unilaterally affected
      animals at ages 4, 6 and 8 weeks were analyzed in this study. Histopathological
      evaluation of spermatogenesis was performed by periodic acid-Schiff-hematoxylin
      staining. To elucidate the pathophysiology of seminiferous tubule damage germ
      cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling and electron microscopy. Four animals
      per group were used for staining and nick end-labeling. RESULTS: Testicular
      weight significantly decreased on the affected side at ages 6 and 8 weeks.
      Impaired spermatogenesis was observed as early as age 4 weeks. Germ cell
      apoptosis was significantly more frequent on the affected side in all age groups
      with the most prominent incidence at age 6 weeks. Most apoptotic germ cells were
      considered spermatocytes. Electron microscopy revealed apoptosis of spermatocytes
      with condensation of chromatins and agglutination of cytoplasmic contents.
      CONCLUSIONS: This study suggests the efficacy of early intervention in patients
      with undescended testes.

PMID- 12050568
TI  - Recovery of erectile function after brief aggressive antihypertensive therapy.
AB  - PURPOSE: We have previously demonstrated that antihypertensive therapy could
      structurally modulate blood vessels in the penis, although the impact on erectile
      function was not established. Given the importance of inadequate penile arterial
      inflow as a cause of erectile dysfunction we determined in spontaneously
      hypertensive rats the impact of brief aggressive antihypertensive therapy on
      structurally based penile vascular resistance, erectile function and mean
      arterial pressure during and after treatment. MATERIALS AND METHODS: Young (15
      week-old) and aged (40-week-old) spontaneously hypertensive rats were treated for
      2 weeks (enalapril 30 mg./kg. daily plus a low salt diet). Mean arterial pressure
      was continuously monitored via radio telemetry. Erectile responses were assessed
      by administering apomorphine (80 microg./kg. subcutaneously) before, during and
      after treatment. Structurally based vascular resistance was determined in the
      isolated, perfused penile vasculature 2 weeks after stopping treatment in aged
      spontaneously hypertensive rats. Certain responses were determined, including
      resistance at maximum dilatation (lumen size) and at maximum constriction (medial
      bulk), and EC50 of the alpha-adrenoceptor agonist methoxamine. RESULTS: In the
      period after the cessation of drug treatment there was a persistent reduction in
      the level of arterial pressure (16%) and a doubling of erectile responses
      compared with pre- treatment. Cardiac and vascular structure regressed, as
      determined by the mean decrease plus or minus standard deviation in vascular
      resistance at maximum dilatation (21% +/- 4.5%) and mean reduction in left
      ventricle mass (10.4% +/- 3.7%). Furthermore, treatment induced a significant
      right shift in alpha1-adrenoceptor concentration response curve in treated versus
      control rats (mean EC50 1.09 +/- 0.111 versus 0.76 +/- 0.111). CONCLUSIONS: The
      improvement in erectile function after brief aggressive treatment may be related
      to improvement in structurally based vascular resistance within the penis and the
      decrease in responsiveness of alpha1-adrenoceptor mediated erectolytic signaling.
      These findings are suggestive of a new therapeutic strategy for hypertension and
      erectile dysfunction.

PMID- 12050569
TI  - Potassium channels and human corporeal smooth muscle cell tone: diabetes and
      relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate
      sensitive potassium channel openers.
AB  - PURPOSE: Sustained contraction of human corporeal smooth muscle depends on
      continuous transmembrane calcium flux through voltage gated calcium channels. K
      channels modulate corporeal smooth muscle membrane potential and, thus,
      ultimately affect transmembrane calcium flux. Therefore, we characterized
      relaxation responses elicited by the K channel modulators pinacidil and
      levcromakalim on isolated human corporeal tissue strips. We also evaluated the
      possibility that there may be alterations in adenosine triphosphate sensitive K
      channel pharmacology/function related to the presence of diabetes mellitus.
      MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips
      obtained from 57 male patients with organic erectile dysfunction were
      investigated. Cumulative concentration-response curves were constructed at half
      log increments for steady state relaxation responses elicited by pinacidil and
      levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75%
      of maximum) isolated corporeal tissue strips. Potassium currents were measured
      using the cell attached whole cell patch clamp technique on freshly isolated
      corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide
      sensitive relaxation response of phenylephrine pre-contracted corporeal tissue
      strips was observed for pinacidil and levcromakalim. Consistent with such
      observations, electrophysiological recordings on freshly isolated myocytes
      revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole
      cell potassium currents that were blocked by glibenclamide (10 microM.). In
      addition, statistical analysis revealed that phenylephrine pre-contracted
      corporeal tissue strips from patients without diabetes were more sensitive to
      relaxation by both compounds than corporeal tissue strips excised from those with
      diabetes. Furthermore, relaxation responses elicited by pinacidil and
      levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were
      completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These
      data indicate that the adenosine triphosphate sensitive K channel subtype is
      likely to have an important role in the relaxation of isolated corporeal tissue
      strips and, moreover, they are the molecular target for the K channel
      modulators/openers levcromakalim and pinacidil. Such observations are consistent
      with the supposition that alterations in the structure/function/activity of these
      potassium channels may underlie at least some aspects of observed diabetes
      related differences in tissue sensitivity to K channel modulators.

PMID- 12050570
TI  - Long-term survival of autotransplanted major pelvic ganglion in the corpus
      cavernosum of adult rats.
AB  - PURPOSE: Neurogenic impotence is a common complication after radical pelvic
      surgery, irradiation or perineal trauma. Neuronal transplantation is a new
      frontier for treating neurological disorders. We investigated whether the major
      pelvic ganglion can survive and become functional after being implanted into the
      corpus cavernosum in adult rats. MATERIALS AND METHODS: Adult male rats (13) were
      divided into 3 groups and sacrificed at 3 time points, namely 30 (4), 60 (5) and
      90 (4) days. All rats underwent excision of the right major pelvic ganglion and
      left cavernous nerve. The right ganglion was implanted into the right crus of the
      penis. Electrostimulation was applied to the left major pelvic ganglion and
      cavernous nerve (1.5 mA.) and right crus (10 mA.) at sacrifice. The crural region
      and left ganglion were then excised for immunostaining of neuronal nitric oxide
      synthase (nNOS), protein gene product 9.5 and growth associated protein 43. Image
      analysis was used to calculate the area stained in pixels. Electron microscopy of
      the implanted area was performed to assess neuronal survival. RESULTS: Although
      the degree varied, all neuronal implants survived after transplantation. The
      response to electrostimulation was insufficient to produce erection. No
      difference was noted among the areas of nNOS staining when specimens from the 3
      time points were compared. The area of expression of nNOS, protein gene product
      9.5 and growth associated protein 43 was larger in the implanted area than in the
      surrounding cavernous tissue. Under electron microscopy most surviving implants
      showed normal ultrastructure, although areas of fibrotic replacement were seen in
      several implants. CONCLUSIONS: Our results show that the autotransplanted major
      pelvic ganglion expresses nNOS, protein gene product 9.5 and growth associated
      protein 43, and survived up to 90 days after implantation into the corpus
      cavernosum. Further studies with fetal neuronal tissue seem warranted.

PMID- 12050572
TI  - Antireflux or antiregurgitation milk products for infants and young children: a
      commentary by the ESPGHAN Committee on Nutrition.

PMID- 12050573
TI  - Lymphoproliferation in children after liver transplantation.

PMID- 12050574
TI  - Genetics of gastroesophageal reflux disease: a review.

PMID- 12050575
TI  - Expanding the definition of GE reflux.

PMID- 12050576
TI  - Amniotic fluid and human milk: a continuum of effect?

PMID- 12050577
TI  - Endoscopic dilatation of esophageal strictures in recessive dystrophic
      epidermolysis bullosa: new equipment, new techniques.

PMID- 12050578
TI  - Esophageal pH monitoring and impedance measurement: a comparison of two
      diagnostic tests for gastroesophageal reflux.
AB  - BACKGROUND: pH monitoring is the standard diagnostic tool for gastroesophageal
      reflux in infants. However, this method does not document the reflux of all kinds
      of fluid from the stomach into the esophagus, but only documents acid material.
      The parameters that define reflux episodes by pH monitoring have been derived
      empirically from observations of many infants considered healthy and ill. Acid
      reflux is a continuum, some reflux is normal and doubt exists as to how much
      reflux is abnormal. In this study, one of the standardized protocols for
      analyzing pH recordings was evaluated and compared with simultaneously obtained
      intraesophageal impedance measurement (IMP), a pH-independent method of detecting
      bolus movement within the esophagus. METHODS: The esophagi of 50 infants with
      reflux symptoms were measured, using both standard pH probe and multiple-site
      impedance measurement. A standard protocol for analyzing esophageal pH records
      was used. The sampling rate for pH values was 15/min. Acid reflux was defined as
      pH less than 4.0 (threshold pH) for at least 15 seconds (minimal duration) with
      at least 30 seconds (latency time) between separate episodes. The software used
      could adjust independently or in combinations the sampling rate and these reflux
      criteria. Thereby it was determined whether changes in the criteria for acid
      reflux improved the sensitivity and predictive value of pH monitoring when
      compared with reflux episodes defined by IMP. RESULTS: During 318 hours of
      recording in 50 infants, 1,887 episodes of reflux occurred according to IMP. Only
      282 (14.9%) of the IMP-determined episodes were acid reflux episodes. No alkaline
      reflux episodes occurred. Among the 270 pH probe-determined episodes using the
      standard criteria of acid reflux, only 153 (sensitivity, 54.3%; positive
      predictive value, 56.7%) were accompanied by unmistakable retrograde bolus
      movement using IMP measurements. Retrograde bolus movement did not accompany the
      other 117 episodes. Using a sampling rate of 15/min, a pH threshold of 4.0, a
      minimal duration of reflux episodes of 8 seconds, and a latency time of 60
      seconds, the positive predictive value of pH probe results increased to 60.7%.
      Variations in the sampling rate or criteria for defining acid reflux did not
      significantly improve the accuracy of the pH probe results versus IMP-defined
      episodes. CONCLUSIONS: Most reflux episodes that occur in infants are
      undetectable by standard pH probe monitoring. pH monitoring does not detect all
      reflux in the esophagus but is useful for detecting acidity in the esophagus and
      determining the duration of its presence. Combining pH monitoring with impedance
      measurement is a valuable diagnostic tool for gastroesophageal reflux in infants.

PMID- 12050579
TI  - Trophic effect of multiple growth factors in amniotic fluid or human milk on
      cultured human fetal small intestinal cells.
AB  - OBJECTIVES: To evaluate the role of growth factors in amniotic fluid and in human
      milk on gastrointestinal adaptation of the fetus and very low-birth-weight
      infants, the effects of these fluids and multiple growth factors were
      investigated in a human fetal small intestinal cell line (FHs 74 Int). METHODS:
      After FHs 74 Int cells were incubated with amniotic fluid, human milk, or
      recombinant growth factors, growth-promoting activity was measured by [3H]
      thymidine incorporation into cells. RESULTS: Incubating cells with amniotic fluid
      or human milk promoted growth dose dependently. Genistein almost completely
      inhibited growth-promoting activity in amniotic fluid P = 0.002), and growth was
      partially inhibited by antibodies against epidermal growth factor (EGF) (P =
      0.047), insulin-like growth factor-1 (IGF-1, P = 0.047), or fibroblast growth
      factor (FGF, P = 0.014). This activity in human milk was inhibited almost
      completely by genistein (P < 0.0001) and partially inhibited by antibodies
      against EGF (P = 0.036), IGF-1 (P = 0.009), FGF (P = 0.004), hepatocyte growth
      factor (HGF, P = 0.001), or transforming growth factor-alpha (TGF-alpha, P =
      0.001). Although recombinant EGF, IGF-1, FGF, HGF, and TGF-alpha elicited a
      synergistic trophic response on cultured cells, the response was much less than
      with amniotic fluid or with human milk. CONCLUSION: In aminiotic fluid and in
      human milk, EGF, IGF-1, FGF, HGF, and TGF-alpha have a strong trophic effect on
      immature intestinal cells and may be involved in perinatal gastrointestinal
      adaptation.

PMID- 12050580
TI  - Reactive nitrogen species modulate the effects of rhein, an active component of
      senna laxatives, on human epithelium in vitro.
AB  - BACKGROUND: Senna laxatives are used worldwide. However, their misuse can lead to
      chronic mucosal inflammation with the accumulation of pigment-laden leukocytes
      and may cause colon cells to undergo apoptosis. This study explores the
      mechanisms by which rhein, an active component of senna, acts on a human
      intestinal cell line to induce ion secretion, apoptosis, and indirect chemotaxis
      of polymorphonuclear leukocytes. METHODS: Human colonic adenocarcinoma (CaCo-2)
      monolayer cells, in the presence or in the absence of rhein, were used to monitor
      the production of reactive nitrogen species using the Griess reaction. Modified
      Ussing chambers were used to study electrolyte secretion. The capacity to recruit
      human polymorphonuclear leukocytes was evaluated using masked well chemotaxis
      chambers. Rhein-induced apoptosis was investigated by counting apoptotic nuclei
      stained with Hoechst 33258 dye. RESULTS: Rhein caused a dose-dependent increase
      in short-circuit current that was abolished in chloride-free bathing buffer or by
      preincubating with 100 micromol/L NG-nitro-L-arginine (L-NAME) methyl ester. The
      concentration that maximally stimulated intestinal secretion, 50 micromol/L
      rhein, induced nitrate production. Supernatants obtained from CaCo-2 cultures
      after incubation with 50 micromol/L rhein stimulated a time-dependent
      polymorphonuclear leukocytes chemotaxis that was significantly decreased with 100
      micromol/L L-NAME, whereas rhein per se was not active. Neutralizing antibodies
      anti-interleukin-8 (IL-8) and anti-ENA78 also inhibited chemotaxis. Overnight
      rhein incubation produced an increased number of apoptotic cells in the culture
      supernatant that was significantly decreased by preincubation with 100 micromol/L
      L-NAME. Light-degraded rhein had no effects on CaCo-2 monolayers. CONCLUSIONS:
      The integrity of rhein is crucial to generating nitric oxide, which mediates,
      with different time courses, ion secretion, chemotaxis, and apoptosis of human
      derived cells.

PMID- 12050581
TI  - Management of esophageal strictures in children with recessive dystrophic
      epidermolysis bullosa.
AB  - BACKGROUND: Recessive dystrophic epidermolysis bullosa is a rare, genetically
      transmitted skin disorder characterized by blister formation and scarring in
      response to minor trauma. One of the most debilitating features of the disease is
      the development of esophageal strictures, which produces profound dysphagia,
      exacerbating an already highly compromised nutritional status common to these
      patients. Due to the extreme fragility of epithelial surfaces, the optimal
      therapeutic approach to esophageal strictures in this setting has not been
      established. METHODS: We have developed an approach to treatment of esophageal
      strictures in children with epidermolysis bullosa combining upper endoscopy using
      small caliber endoscopes, endotracheal intubation, and fluoroscopically assisted
      balloon dilatation. We report our experience using this technique in 22 children
      who have undergone a total of 109 dilatations. RESULTS: Upper endoscopy,
      endotracheal intubation, and balloon dilatation were well tolerated by even very
      young children with epidermolysis bullosa. Dysphagia was markedly reduced post
      procedure, permitting resumption of normal diet for age, including solids, within
      six hours of the procedure. Post-procedure recovery has been rapid and does not
      require admission to the hospital. Complications have been infrequent, minor, and
      limited to the first year of our experience. The mean interval between
      dilatations for all children is 11 months. All children have gained weight, and
      have not required steroids or phenytoin. CONCLUSIONS: Balloon dilatation is a
      safe and effective therapy for esophageal strictures in children with recessive
      dystrophic epidermolysis bullosa. Limited upper endoscopy and endotracheal
      intubation are well tolerated by these children. This approach should be
      considered as primary therapy in this clinical setting.

PMID- 12050582
TI  - Neonatal hypoxia in the rat: effects on exocrine pancreatic development.
AB  - BACKGROUND: Glucocorticoids profoundly affect pancreatic development during the
      suckling period. Increases in circulating glucocorticoids during exposure to
      hypoxia may alter the normal pattern of pancreatic enzyme development. METHODS:
      Rats were exposed to hypoxia from birth to 7 days (suckling) or from 28 to 35
      days of age (weaned at day 21). RESULTS: Hypoxia in neonatal rats (0-7 days) led
      to decreased pancreatic weight, and trypsin, lipase, and amylase activity
      compared with normoxic controls. In contrast, rats exposed to hypoxia from 28 to
      35 days of age had decreased lipase activity but no change in other pancreatic
      parameters. Two weeks after hypoxia (0-7 days) pups were returned to normoxia,
      and their body weights remained smaller than the age-matched, previously normoxic
      controls. Pancreatic enzyme activities were decreased in the group recovering
      from hypoxia compared with controls. Recovery of enzyme activities was observed 3
      weeks after hypoxic rats were returned to normoxia. Normoxic pups were given
      dexamethasone to simulate the hyperglucocorticoid state in hypoxia at 7-day olds.
      Dexamethasone administration led to decreased body weight, but increased
      pancreatic weight and enzyme activity compared with normoxic, age-matched
      controls. CONCLUSIONS: Hypoxia in newborn rats delays the maturation of
      pancreatic exocrine enzymes. The mechanism is not related to increased serum
      glucocorticoids.

PMID- 12050583
TI  - HLA-DQA1 and HLA-DQB1 genetic markers and clinical presentation in celiac
      disease.
AB  - BACKGROUND: Patients with celiac disease are diagnosed at any age and can exhibit
      a wide range of clinical manifestations. The reasons for this are unclear. The
      aim of this study was to investigate a possible correlation between the HLA-DQA1
      and HLA-DQB1 genetic markers and clinical features of celiac disease. METHODS: A
      total of 133 patients with celiac disease were tested for the HLA-DQA1 and HLA
      DQB1 genes. Their corresponding allele and haplotype frequency distributions were
      estimated from the phenotypes found. The results were correlated with data from
      the clinical records. RESULTS: The DQ2 molecule was found in 93% of the patients,
      and DQ2 or DQ8 was found in 98%. The DQA1*0201-DQB1*0202 haplotype showed strong
      linkage disequilibrium. DQ2 homozygosis was significantly associated with female
      sex, earlier age at diagnosis, and shorter delay between onset of symptoms and
      diagnosis. Double-dose DQB1*02 (01-02) allele was more frequent in patients with
      the classic presentation of the disease. CONCLUSIONS: The genetic markers
      investigated may prove useful for diagnosing and managing celiac disease. With
      some clinical variables, correlations not previously described were found. These
      correlations have a moderate strength and, therefore, must be confirmed by other
      studies.

PMID- 12050584
TI  - Successful topical tacrolimus (FK506) therapy in a child with pyoderma
      gangrenosum.

PMID- 12050585
TI  - Resolution of severe peristomal pyoderma gangrenosum with infliximab in a child
      with Crohn disease.

PMID- 12050586
TI  - Transhepatic hickman line placement: improving line stability by surgically
      assisted radiologic placement.

PMID- 12050587
TI  - Gastric diverticulum: a series of four pediatric patients.

PMID- 12050588
TI  - Migration of percutaneous endoscopic gastrostomy tube in children.

PMID- 12050589
TI  - Re: Phytoestrogens: the pediatric perspective.

PMID- 12050592
TI  - [Chemical drug development].

PMID- 12050590
TI  - Measurement of oro-cecal transit time in young children using lactose [13C]
      ureide requires further validation.

PMID- 12050594
TI  - [Crystallization and solid state properties of molecules of pharmaceutical
      interest].
AB  - Polymorphism characterizes the ability of a molecule to crystallize in different
      crystallographic systems (in the case of a simple atom the term allotropy is
      used). This phenomenon, known for a long time, leads to significantly different
      physicochemical properties between the different crystalline forms. In the
      pharmaceutical domain, the potential polymorphism of the active substances and
      the excipients could affect Since most of the pharmaceutical products consist of
      solid dosage forms administered by the oral route, it is not surprising that
      studies on polymorphism have become a mandatory chapter of any pharmaceutical
      dossier whether it concerns a new chemical entity or a generic. In fact, beyond
      the polymorphism phenomenon, it is the crystallization process which deserves to
      be highlighted. We will show how it controls the appearance of the polymorphism
      and the crystalline growth which is a second feature at least as important as the
      polymorphism itself (external aspect of the solid particles/habit) in terms of
      processability and dissolution. After having recalled some thermodynamic
      considerations which characterize the polymorphism, we will illustrate succinctly
      the impact of these phenomena on some important aspects of the pharmaceutical
      development such as the dissolution, the bioavailability and the stability.

PMID- 12050595
TI  - [Crystalline modifications and polymorphism changes during drug manufacture].
AB  - More than half of the pharmaceutical compounds exhibit polymorphism or
      pseudopolymorphism, e.g., they exist as more than one crystalline structure (true
      polymorphs, hydrates, solvates) or as more or less amorphous products. As such,
      they show at the solid state different physicochemical properties (melting point,
      transition point, plasticity, solubility, hygroscopicity, chemical reactivity),
      which in turn may affect the technological and biopharmaceutical properties of
      active ingredients or excipients (compactibility, dissolution rate,
      bioavailability, pharmacological activity, stability). When considering a
      chemically well-defined compound, one may find one or another crystalline state
      or polymorphic form according to the source or batch considered. One may also
      observe changes in technological or biopharmaceutical properties that are due to
      polymorphic transformations arising from the mechanical or heat treatment or from
      the environmental conditions (solvent-mediated reactions, desolvation) undergone
      by the product or the dosage form. The present article presents the fundamental
      aspects related to the above-mentioned phenomena and reviews both classical and
      recent examples from the literature reporting transformations during milling or
      grinding, tabletting, preparation of drug suspensions, granulation, dissolution
      or release tests, stability trials, spray drying, freeze-drying or preparation of
      adsorbates or complexes.

PMID- 12050596
TI  - [Crystalline polymorphism of eflucimibe].
AB  - The importance, in therapeutics, of the concept of bioavailability and on-going
      quality research in the formulation of a drug has prompted us to examine the
      crystalline polymorphism of eflucimibe as from the research phase. This study has
      been carried out by re-crystallization of the product in organic solvents having
      a different polarity in a variety of experimental temperature and pressure
      conditions, then, subsequently, by re-cooling the previously dissolved substance.
      The analytical methods applied to identify and then describe the polymorphic
      forms are thermogravimetry analysis (TGA), differential scanning calorimetry
      (DSC), X-ray powder diffraction from synchrotron radiation (XRPD), infrared
      spectrometry (IR), solid-state nuclear magnetic resonance spectrometry (SSNMR)
      and lastly maximum solubility measurements. By means of XRPD, two polymorphic
      forms called A and B have been clearly identified at ambient temperature. These
      two crystalline forms were obtained in a reproducible way, then described by DSC,
      XRPD, IR and SSNMR. Differential scanning calorimetry analysis has shown for
      polymorphic form A two endothermic phenomena with low energy at about 35
      masculine and 118 degrees C attributed by XRDP to conformational polymorphism.
      The complex endothermic event that extends between 75 masculine and 105 degrees C
      appears to correspond to successive alterations of a lamellar structure. The
      solid-solid transition observed at 110 degrees C is due to a change of
      crystalline phase, then the melting point occurring at about 130 degrees C. For
      form B, two changes of crystalline phase are clearly observed at about 80
      masculine and 120 degrees C. The reversibility of these changes was observed by
      thermomicroscopy in polarized light. Form A, which is less soluble in absolute
      ethanol than form B, is the more stable thermodynamically in the temperature
      range from 25 masculine to 50 degrees C where the data have been obtained. The
      Van't Hoff diagram layout for each polymorphic form appears to reveal an A<-->B
      transition temperature in a temperature range lower than 25 degrees C. This
      study, undertaken as from the research phase, has enabled us to highlight the
      polymorphism of this new chemical entity by means of XRDP by explaining the
      nature of the endothermic phenomena observed by DSC, and lastly identify the
      thermodynamically more stable polymorphic form, thus contributing to a better
      knowledge of this future drug.

PMID- 12050597
TI  - [Crystallography of drug polymorphism: emergence of new resolution methods and
      prediction of crystalline structures].
AB  - For the pharmaceutical and agrochemical industries, reducing development time is
      currently a primary objective to accelerate the marketing of new products. In
      depth solid-state characterization is an essential element in achieving this
      performance. For this purpose, it is now recognized that, in a department of
      solid-state physical characterization, theoretical approaches have to be
      integrated with experimental tools. Benefiting from the constant improvement in
      computer hardware and software in terms of computing powers and algorithm
      development, these approaches appear to be a complementary method that can help
      explain and rationalize experimental data. In recent years, with the help of both
      molecular modeling tools and crystallographic databases, original methods have
      been developed and successfully applied to systems of variable complexity. The X
      ray diffraction crystal structure determination makes it possible to calibrate
      the force field and to adapt it more precisely to the compound studied, thereby
      reducing one of the sources of uncertainty. Although crystal structures are
      preferentially determined from single crystal data, it has been recently shown
      that powder diffraction data can also be used when single crystals are missing.
      Therefore, the different benefits of such an approach are the following: ab
      initio predictive study of crystalline polymorphism, molecular packing analysis
      and detection of cleavage planes, prediction of morphology in vacuum. In
      conjunction with crystallite preferred orientation observed in powder patterns,
      grinding effects on the crystal habit and solvent effects in modifying growth can
      be clearly understood. Selected industrial cases exemplify the operational
      application of this methodology.

PMID- 12050598
TI  - [Thermodynamics of drug polymorphism: domains and stability hierarchy by pressure
      temperature diagram. Application to the tetramorphism of fananserine].
AB  - In this communication, an application of classical thermodynamics to crystalline
      solid state polymorphism is shown to allow stability p, T domains and stability
      hierarchy among crystalline phases of a polymorph to be defined by constructing
      the unary p, T phase diagram. The three topological rules upon which this
      construction is founded are presented; the first one is a straight consequence of
      the least vapour pressure criterion by Ostwald. Calculation of triple point co
      ordinates and of two-phase equilibrium curves is based upon using both
      thermodynamic and crystallographic data obtained at ordinary pressure. Clapeyron
      equation allows the slopes of the straight lines representing equilibria between
      condensed phases to be calculated and, hence, triple points situated at high or 
      negative  pressure to be determined. On the other hand, the hierarchy among the
      thermodynamic stability degrees of the crystalline varieties may be inferred from
      the location of the sublimation curves, by merely acknowledging inequalities
      among vapour pressures at each temperature on the whole T-range. These building
      up processes are pointed out by outlining the achievement of a phase diagram
      related to the tetramorphism of fananserine, an anxiolytic drug. Three out four
      crystalline forms, namely phases II, III and IV, possess their own stability
      domain, although those belonging to phases II and III are limited at high
      pressure by that of phase IV. Conversely, phase I is overall metastable and
      exhibits a whole monotropic behaviour.

PMID- 12050599
TI  - [Conclusion: crystalline polymorphism and therapeutic activity: a crossroad of
      two cultures?].

PMID- 12050600
TI  - Four-dimensional reconstruction of the left ventricle using a fast rotating
      classical phased array scan head: preliminary results.
AB  - The evaluation of left ventricular function by noninvasive methods is still a
      major problem in cardiology. Two-dimensional echocardiography requires mental
      reconstruction of the heart by the physician and is always based on approximation
      of heart shapes and volumes. Three-dimensional echocardiography is promising but
      has rhythmic and function constraints because of the acquisition during many
      cardiac cycles. This article reports a study carried out to validate a new 4
      dimensional echocardiography method. With the use of a classical phased-array
      sensor with a fast rotating motorized motion and a standard ultrasound system,
      many slices at different angulations are obtained in a single cardiac cycle.
      After manual endocardial delineation and computation, a representation of the
      left ventricle (beating heart) and a volume quantification are obtained at each
      instant of the cardiac cycle. This method has been tested on 11 healthy
      volunteers and the results are in agreement with those obtained with standard 2
      dimensional echocardiography. Because of its simplicity of operation and short
      time acquisition, this new imaging modality is highly valuable in left ventricle
      evaluation, even if further studies on pathologic hearts need to be performed.

PMID- 12050601
TI  - Echocardiographic evaluation of ventricular remodeling in a mouse model of
      myocardial infarction.
AB  - Gene-targeting in mice is a powerful tool to define molecular mechanisms of
      ischemic heart disease that determine infarct size, postinfarct left ventricular
      (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a
      widely used model of myocardial infarction (MI), but the pathophysiologic
      consequences of MI in mice and its relevance to human MI have not been fully
      elucidated. To characterize structural and functional changes during evolving MI,
      we analyzed 2-dimensional-based reconstruction of the left ventricle by
      noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of
      the left anterior descending coronary artery in mice. Sequential 2-dimensional
      short-axis cineloops of the left ventricle were used to measure LV mass, and LV
      volumes at end-diastole and end-systole. Echocardiographic infarct size was
      estimated by measuring the volume of akinetic LV segments. Histologic infarct
      size was measured by planimetry of 9 transverse sections of each heart. There was
      close correlation between the 2 methods (31% +/- 20% of LV mass and 34% +/- 17%
      of LV area, respectively; y =.83x + 7.9, r = 0.96, P <.01). LV volumes at end
      diastole increased significantly between 1 day and 1 week (51 +/- 17 microL vs 78
      +/- 46 microL, respectively, P <.05). The relative change in LV volumes at end
      diastole varied as a function of infarct size (r = 0.93, P <.01). LV mass and the
      extent of hypertrophy of noninfarcted segments also varied with infarct size (r =
      0.92, P <.01; r = 0.90, P <.01, respectively). Thus, echocardiography is an
      accurate noninvasive tool for determination of infarct size and quantitative
      characterization of postinfarct remodeling in the mouse model of MI. Alterations
      in cardiac structure and function after coronary ligation in mice closely
      resemble pathophysiologic changes in human ischemic heart disease.

PMID- 12050602
TI  - Minor segmental dyssynergy reflects extensive myocardial damage and global left
      ventricle dysfunction in chronic Chagas disease.
AB  - The majority of patients with Chagas disease (ChD) remain for 10 to 30 years or
      even for life in the indeterminate form (IF) of this disease. They have positive
      specific serology tests for ChD, but no symptoms or physical signs, and normal
      findings for electrocardiograms (ECGs) and heart, esophagus, and colon
      radiographs. To investigate whether patients in this phase of disease have any
      impairment of left ventricular (LV) systolic performance, we assessed their
      contractility index by the slope of the LV end-systolic pressure-dimension (P(es)
      D(es)) relation. We studied 35 patients with ChD (14 IF, 11 digestive form [DF],
      10 cardiac form [CF]) and 13 healthy subjects. Patients with the CF had only
      minor cardiac involvement (bundle-branch block, normal LV ejection fraction). All
      patients had normal baseline global LV systolic function on 2-dimensional
      echocardiography, but minor segmental wall motion abnormalities were observed in
      3 DF, 3 IF, and 2 CF patients. At rest and during intravenous phenylephrine
      infusion, we measured LV dimensions by echocardiography, and LV end-systolic
      pressure was estimated by a calibrated carotid pulse tracing. We also measured
      percent fractional shortening (%DeltaD) and the rate-corrected mean velocity of
      fiber shortening (Vcf(c)). Mean values (+/- SD) of %DeltaD and Vcf(c) were not
      significantly different from those exhibited by healthy control subjects in any
      of the ChD groups at rest (except for CF) or at peak stress using phenylephrine.
      The P(es)-D(es) slope was similarly and significantly reduced in all ChD patients
      (IF: 50.7 +/- 25; DF: 52.3 +/- 24; CF: 60.8 +/- 22 mm Hg/cm) compared with normal
      subjects (89 +/- 17 mm Hg/cm). The P(es)-D(es) slope was even more depressed
      (39.6 +/- 10 mm Hg/cm) in ChD patients who had minor segmental wall motion
      abnormalities (SWMAs) on the baseline 2-dimensional echocardiograph in comparison
      with the slightly reduced values found in patients with CF who had isolated
      conduction abnormalities on the ECG (71.8 +/- 10 mm Hg/cm). Although %DeltaD and
      Vcf(c), even at peak afterload, do not differentiate ChD patients from normal
      controls, the P(es)-D(es) slope is significantly impaired in IF, DF, and CF
      patients. The remarkably lower P(es)-D(es) slope value documented in ChD patients
      exhibiting only minor LVWMAs suggests a more extensive myocardial damage in this
      group of patients, indicating that they should be considered as exhibiting
      symptoms of the CF version of the disease.

PMID- 12050603
TI  - Diagnosis of vasospastic angina by hyperventilation and cold-pressor stress
      echocardiography: comparison to I-MIBG myocardial scintigraphy.
AB  - OBJECTIVES: We assessed the usefulness of hyperventilation and cold-pressor
      stress echocardiography in the diagnosis of vasospastic angina compared with that
      of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy.
      BACKGROUND: Various noninvasive methods have been used to detect vasospastic
      angina, but they are not very sensitive in the diagnosis of vasospastic angina.
      123I-MIBG images and stress echocardiography have recently been proposed as a
      useful tool for detecting vasospastic angina. METHOD: Thirty patients (21 males
      and 9 females, mean age: 52 +/- 14 years) who complained of rest angina were
      enrolled for this study. The hyperventilation and cold-pressor stress
      echocardiography test consisted of hyperventilation for 6 minutes, followed by
      cold water pressor for 2 minutes under continuous electrocardiographic and
      echocardiographic monitoring. Left ventricular regional wall motion by
      echocardiogram was analyzed by using the 16-segment model, and wall motion
      ranging from normokinesis to dyskinesis was evaluated visually in each segment.
      Single-photon emission computed tomography images of 123I-MIBG myocardial
      scintigraphy were divided into 26 segments. Defect scores were established using
      the 4 grades. The echocardiographic criteria for coronary spasm was worsening
      wall motion and the scintigraphic criteria was defect score more than moderately
      reduced. Acetylcholine was selectively injected into the right coronary artery
      (20 microg and 50 microg) and left coronary artery (20 microg, 50 microg, and 100
      microg). RESULTS: Of 30 patients, 20 patients had coronary spasm on coronary
      angiography with an intracoronary injection of acetylcholine, whereas 10 patients
      showed no spasm. Multivessel spasms were observed in 15 patients. Sensitivity,
      specificity, positive predictive value, negative predictive value, and diagnostic
      accuracy of hyperventilation and cold-pressor stress echocardiography for
      diagnosing in patients with vasospastic angina were 90%, 90%, 95%, 82%, and 90%,
      respectively. However, those of 123I-MIBG myocardial scintigraphy for diagnosing
      in patients with vasospastic angina were 90%, 40%, 75%, 67%, and 73%,
      respectively. The specificity of hyperventilation and cold-pressor stress
      echocardiography was significantly higher than that of 123I-MIBG myocardial
      scintigraphy (P <.05). CONCLUSION: The specificity of hyperventilation and cold
      pressor stress echocardiography in diagnosing coronary spasm were higher than
      that shown by 201I-MIBG myocardial scintigraphy.

PMID- 12050604
TI  - Quantification of the myocardial velocity gradient and myocardial wall thickening
      velocity in healthy children: a new indicator of regional myocardial wall motion.
AB  - Doppler tissue imaging allows the measurement of tissue motion velocity in real
      time. However, tissue velocities are affected by translational motion and by the
      angle of Doppler interrogation. The myocardial velocity gradient and myocardial
      wall thickening velocity, determined by color Doppler tissue imaging, can be used
      to evaluate regional wall thickening and thinning motion independent of
      translational motion. To determine the control values for myocardial velocity
      gradient and myocardial wall thickening velocity for the interventricular septum
      and posterior wall, we studied 120 healthy children (mean age: 7.8 +/- 5.0
      years). Peak values of myocardial velocity gradient and myocardial wall
      thickening velocity at each cardiac phase were measured: systole, early diastole,
      and atrial contraction. The peak values of myocardial velocity gradient and
      myocardial wall thickening velocity were higher in the posterior wall than those
      in the interventricular septum, suggesting that thickening and thinning are more
      dynamic in the posterior wall. Linear regression analysis demonstrated that
      absolute values of myocardial velocity gradient at systole, early diastole, and
      atrial contraction, and wall thickening velocity at atrial contraction decreased
      with body surface area (BSA). On the other hand, absolute values of myocardial
      wall thickening velocity at systole and early diastole increased with BSA, and
      myocardial wall thickening velocity at early diastole in interventricular septum
      did not change. Myocardial velocity gradient at systole and early diastole, and
      myocardial wall thickening velocity at systole were strongly related to BSA. In
      contrast, myocardial velocity gradient and myocardial wall thickening velocity at
      atrial contraction strongly correlated with time interval between 2 consecutive
      QRS complexes. Because myocardial wall thickening velocity at early diastole in
      the interventricular septum did not correlate with BSA or time interval between 2
      consecutive QRS complexes, it might evaluate diastolic function of
      interventricular septum independent of body size or heart rate.

PMID- 12050605
TI  - Comparison of echocardiographic markers of right ventricular function in
      determining prognosis in chronic pulmonary disease.
AB  - Right ventricular (RV) dysfunction determines prognosis in patients with chronic
      pulmonary disease. We examined the relative prognostic potential of measures of
      systolic, diastolic, and global RV function in 87 patients with chronic pulmonary
      disease. Systolic function was evaluated by measuring RV dimensions, diastolic
      function by pulsed wave Doppler of the tricuspid flow profile, and global
      function by the Tei index. After 15.5 months follow-up, 47 patients had died.
      Univariate analysis demonstrated that both clinical and echocardiographic
      variables predicted survival. In the multivariate model both RV end-diastolic
      diameter index and velocity of late diastolic filling were independent predictors
      of survival. Receiver operator characteristic analysis demonstrated that a
      composite model combining these 2 measures provided the most powerful prognostic
      information. Echocardiographic indices of RV function identify patients with
      pulmonary disease at high risk and provide incremental prognostic information
      over and above that supplied by clinical data.

PMID- 12050606
TI  - Limited cardiac ultrasound examination for cost-effective echocardiographic
      referral.
AB  - BACKGROUND: Although a standard echocardiogram is frequently requested and
      requires significant resources, few data exist on methods to improve referral for
      this examination. Therefore, we sought to determine the diagnostic value of a
      limited echocardiographic examination and to predict the cost-effectiveness of a
      limited imaging strategy on echocardiographic referral. METHODS: A limited
      echocardiographic examination was reviewed for abnormalities and compared with
      standard echocardiographic findings. Assuming an imaging strategy in which a
      normal limited echocardiographic examination would negate the need for standard
      echocardiography, we calculated the diagnostic yields, the number of full
      echocardiographic studies eliminated, and the number of abnormal cases missed. We
      also stratified data by patient age (< or > or = 65 years), inpatient versus
      outpatient status, gender, referral diagnosis, and referring physician
      subspecialty. RESULTS: In 151 outpatients, overall diagnostic yield was 47% (95%
      CI [39%, 55%]), and was lower in those younger than 65 years, in women, and in
      noncardiologist referral. In 155 inpatients, yields were 75% (95% CI [67%, 83%])
      and were also related to age, but not to gender, diagnosis, and physician
      subspecialty. Sensitivity, specificity, negative and positive predictive values,
      and accuracy for the limited echocardiographic examination was 77%, 72%, 67%,
      81%, and 75%, respectively. The limited imaging strategy negated 70% of studies
      in the outpatient group younger than 65 years, with a less than 5% chance of
      missing a clinically significant finding. CONCLUSION: A limited echocardiographic
      imaging strategy is most cost-effective when used in young outpatients, where it
      can result in a substantial reduction in referral for standard echocardiography
      while rarely missing findings.

PMID- 12050607
TI  - American Society of Echocardiography and Society of Cardiovascular
      Anesthesiologists task force guidelines for training in perioperative
      echocardiography.

PMID- 12050608
TI  - Reversal of Phen-Fen associated valvular regurgitation documented by serial
      echocardiography.
AB  - We report a case of anorexigen-associated moderate to severe aortic and mitral
      regurgitation in which the regression of lesions was marked and well documented
      over more than 2 years. The stability of our patient, as well as the degree of
      regression of regurgitation documented in our patient, and others, suggests it is
      prudent both to observe such patients and to avoid operation until such
      observation has been carried out.

PMID- 12050609
TI  - Aortic valve commissural tear mimicking type A aortic dissection.
AB  - A 52-year-old man came to the local emergency department with symptoms of heart
      failure and transient chest pain. Transthoracic echocardiography showed severe
      aortic regurgitation and a dilated ascending aorta. Aortic dissection was
      suspected, and he was transferred to our institution. Transesophageal
      echocardiography appeared to confirm the presence of a type A dissection. A
      mobile, linear structure was present in the proximal ascending aorta, suggesting
      the presence of dissection flap. Aortic cusp prolapse and severe aortic
      regurgitation were seen. At surgery, no aortic dissection was present. Rather,
      the commissure between right and left aortic valve cusps was separated from the
      wall of the aorta. Motion of the torn commissure with the cardiac cycle
      apparently led to the transesophageal echocardiographic appearance described. The
      ascending aorta was dilated. Histopathologic examination of the aorta confirmed
      the visual appearance of cystic medial necrosis. Aortic valve commissural tear is
      a rare event, which may lead to severe aortic regurgitation. This entity may lead
      to the false-positive transesophageal echocardiographic diagnosis of type A
      dissection.

PMID- 12050610
TI  - Echocardiographic diagnosis of an asymptomatic aneurysm of a saphenous vein
      graft.
AB  - A case of a 73-year-old asymptomatic man with a large saphenous vein graft
      aneurysm first diagnosed 16 years after bypass operation is presented. The lesion
      was first suspected on routine transthoracic echocardiography and further
      clarified by transesophageal echocardiography. Selective graft angiography
      confirmed the diagnosis and surgical therapy included resection of the graft
      aneurysm and coronary artery bypass grafting.

PMID- 12050611
TI  - Exceptional survival of a patient with large ventricular septal defect,
      bidirectional shunt, and severe pulmonary valve stenosis.
AB  - A 74-year-old man has survived in good health for an exceptionally long time
      despite the presence of a moderate-to-large-sized membranous ventricular septal
      defect (VSD). He has remained acyanotic with New York Heart Association class I
      function. Transthoracic and transesophageal echocardiography with color flow
      Doppler demonstrated a membranous VSD with left-to-right and right-to-left
      bidirectional shunts during ventricular systole and diastole, respectively, with
      an right ventricular systolic pressure of 93 mm Hg, dilation of the atria and the
      right ventricle, and right ventricular hypertrophy. The pulmonary valve was
      severely stenotic with transpulmonary valve peak velocity of 6.1 m/s and a peak
      pressure gradient of 147 mm Hg. The pulmonary artery and inferior vena cava were
      mildly dilated, and the left ventricular dimension and systolic function were
      normal. Transesophageal echocardiography with saline solution microbubble
      injection demonstrated positive contrast effect in the left ventricle in diastole
      confirming a right-to-left shunt at the ventricular level. This man is currently
      the oldest survivor with a moderate-to-large-sized membranous VSD reported in the
      literature.

PMID- 12050612
TI  - Unruptured sinus of Valsalva aneurysm in an asymptomatic patient.
AB  - A 75-year-old asymptomatic male patient was referred for transesophageal
      echocardiography after detection of a diastolic murmur on routine physical
      examination and widened mediastinum on a chest radiograph. Transesophageal
      echocardiography revealed a large, unruptured sinus of Valsalva aneurysm, filled
      with a thrombus and spontaneous echocontrast and protruding into the right
      atrium. Unruptured sinus of Valsalva aneurysms are rare, frequently asymptomatic,
      and not associated with any physical findings. The diagnosis was made by
      transesophageal echocardiography and was confirmed by angiography and at surgery.
      The need for corrective surgery of asymptomatic, incidentally diagnosed sinus of
      Valsalva aneurysm is not well defined in the absence of precise knowledge of its
      natural history. We provide a description of the natural history and rationale
      for early corrective surgery of sinus of Valsalva aneurysms in asymptomatic
      patients.

PMID- 12050614
TI  - The best of both worlds. Seattle.

PMID- 12050616
TI  - Genomics and taxonomy for all.
AB  - Principles of access to public and private databases are often contentious, and a
      proposal in this issue will no doubt spark more debate. Meanwhile, Nature is
      taking a small step towards a database for taxonomists.

PMID- 12050617
TI  - Alpine detector fails to confirm Italian sighting of dark matter.

PMID- 12050624
TI  - Ecologist sues over wrecked iguana study.

PMID- 12050626
TI  - Joint projects see ocean science aiming high.

PMID- 12050629
TI  - Flying free.

PMID- 12050630
TI  - Therapeutic antibodies: magic bullets hit the target.

PMID- 12050631
TI  - Knowledge about animal suffering is too rarely used.

PMID- 12050632
TI  - Conceptual biology: a semantic issue and more.

PMID- 12050633
TI  - Bioinformatics code must enforce citation.

PMID- 12050634
TI  - Uncovering the complex mysteries of mosaicism.

PMID- 12050635
TI  - The times they are a-changin'.

PMID- 12050641
TI  - Fibonacci's flowers.

PMID- 12050642
TI  - Iodine's air of importance.

PMID- 12050644
TI  - Indirect evidence.

PMID- 12050643
TI  - Developmental genetics: buffer zone.

PMID- 12050645
TI  - Neurobiology: glutamate receptors on the move.

PMID- 12050648
TI  - The Hoyle story.

PMID- 12050649
TI  - Developmental neurobiology: cortical liars.

PMID- 12050651
TI  - Marine iguanas die from trace oil pollution.
AB  - An oil tanker ran aground on the Galapagos island of San Cristobal on 17 January
      2001, spilling roughly three million litres of diesel and bunker oil. The slick
      started to spread westwards and was dispersed by strong currents, so only a few
      marine animals were killed immediately as a result. Here we draw on the long-term
      data sets gathered before the spill to show that a population of marine iguanas
      (Amblyrhychus cristatus) on Sante Fe island suffered a massive 62% mortality in
      the year after the accident, due to a small amount of residual oil contamination
      in the sea. Another population on the more remote island of Genovesa was
      unaffected.

PMID- 12050652
TI  - Ecology: Darwin's naturalization hypothesis challenged.
AB  - Naturalized plants can have a significant ecological and economic impact, yet
      they comprise only a fraction ot the plant species introduced by humans. Darwin
      proposed that introduced plant species will be less likely to establish a self
      sustaining wild population in places with congeneric native species because the
      introduced plants have to compete with their close relatives, or are more likely
      to be attacked by native herbivores or pathogens, a theory known as Darwin's
      naturalization hypothesis. Here we analyze a complete list of seed-plant species
      that have been introduced to New Zealand and find that those with congeneric
      relatives are significantly more, not less, likely to naturalize--perhaps because
      they share with their native relatives traits that pre-adapt them to their new
      environment.

PMID- 12050653
TI  - Palaeobiology: calcification of early vertebrate cartilage.
AB  - Hagfish and lampreys are unusual for modern vertebrates in that they have no jaws
      and their skeletons are neither calcified nor strengthened by collagen   the
      cartilaginous elements of their endoskeleton are composed of huge, clumped
      chondrocytes (cartilage cells). We have discovered that the cartilage in a 370
      million-year-old jawless fish, Euphanerops longaevus, was extensively calcified,
      even though its cellular organization was similar to the non-mineralized type
      found in lampreys. The calcification of this early lamprey-type cartilage differs
      from that seen in modern jawed vertebrates, and may represent a parallel
      evolutionary move towards a mineralized endoskeleton.

PMID- 12050654
TI  - Microbial evolution: antitoxin vaccines and pathogen virulence.
AB  - In their mathematical description of vaccine-induced immunity, Gandon et al.
      predict that the host's immunity to a microbial toxin will lead to increased
      virulence of the pathogen without affecting its transmission. However, results
      obtained using vaccines against two additional bacterial pathogens are not
      consistent with this prediction. The model proposed by Gandon et al. may
      therefore be an oversimplification, with the outcome depending on the biological
      details of both the pathogen and the vaccine.

PMID- 12050656
TI  - Computational and evolutionary aspects of language.
AB  - Language is our legacy. It is the main evolutionary contribution of humans, and
      perhaps the most interesting trait that has emerged in the past 500 million
      years. Understanding how darwinian evolution gives rise to human language
      requires the integration of formal language theory, learning theory and
      evolutionary dynamics. Formal language theory provides a mathematical description
      of language and grammar. Learning theory formalizes the task of language
      acquisition it can be shown that no procedure can learn an unrestricted set of
      languages. Universal grammar specifies the restricted set of languages learnable
      by the human brain. Evolutionary dynamics can be formulated to describe the
      cultural evolution of language and the biological evolution of universal grammar.

PMID- 12050657
TI  - Hsp90 as a capacitor of phenotypic variation.
AB  - Heat-shock protein 90 (Hsp90) chaperones the maturation of many regulatory
      proteins and, in the fruitfly Drosophila melanogaster, buffers genetic variation
      in morphogenetic pathways. Levels and patterns of genetic variation differ
      greatly between obligatorily outbreeding species such as fruitflies and self
      fertilizing species such as the plant Arabidopsis thaliana. Also, plant
      development is more plastic, being coupled to environmental cues. Here we report
      that, in Arabidopsis accessions and recombinant inbred lines, reducing Hsp90
      function produces an array of morphological phenotypes, which are dependent on
      underlying genetic variation. The strength and breadth of Hsp90's effects on the
      buffering and release of genetic variation suggests it may have an impact on
      evolutionary processes. We also show that Hsp90 influences morphogenetic
      responses to environmental cues and buffers normal development from destabilizing
      effects of stochastic processes. Manipulating Hsp90's buffering capacity offers a
      tool for harnessing cryptic genetic variation and for elucidating the interplay
      between genotypes, environments and stochastic events in the determination of
      phenotype.

PMID- 12050658
TI  - Observational evidence for the accretion-disk origin for a radio jet in an active
      galaxy.
AB  - Accretion of gas onto black holes is thought to power the relativistic jets of
      material ejected from active galactic nuclei (AGN) and the 'microquasars' located
      in our Galaxy. In microquasars, superluminal radio-emitting features appear and
      propagate along the jet shortly after sudden decreases in the X-ray fluxes. This
      establishes a direct observational link between the black hole and the jet: the X
      ray dip is probably caused by the disappearance of a section of the inner
      accretion disk as it falls past the event horizon, while the remainder of the
      disk section is ejected into the jet, creating the appearance of a superluminal
      bright spot. No such connection has hitherto been established for AGN, because of
      insufficient multi-frequency data. Here we report the results of three years of
      monitoring the X-ray and radio emission of the galaxy 3C120. As has been observed
      for microquasars, we find that dips in the X-ray emission are followed by
      ejections of bright superluminal knots in the radio jet. The mean time between X
      ray dips appears to scale roughly with the mass of the black hole, although there
      are at present only a few data points.

PMID- 12050659
TI  - Coherence incoherence and dimensional crossover in layered strongly correlated
      metals.
AB  - The properties of an interacting electron system depend on the electron
      correlations and the effective dimensionality. For example, Coulomb repulsion
      between electrons may inhibit, or completely block, conduction by intersite
      electron hopping, thereby determining whether a material is a metal or an
      insulator. Furthermore, correlation effects increase as the number of effective
      dimensions decreases; in three-dimensional systems, the low-energy electronic
      states behave as quasiparticles, whereas in one-dimensional systems, even weak
      interactions break the quasiparticles into collective excitations. Dimensionality
      is particularly important for exotic low-dimensional materials where one- or two
      dimensional building blocks are loosely connected into a three-dimensional whole.
      Here we examine two such layered metallic systems with angle-resolved
      photoemission spectroscopy and electronic transport measurements, and we find a
      crossover in the number of effective dimensions from two to three with decreasing
      temperature. This is apparent from the observation that, in the direction
      perpendicular to the layers, the materials have an insulating character at high
      temperatures but become metal-like at low temperatures, whereas transport within
      the layers remains metallic over the whole temperature range. We propose that
      this change in effective dimensionality correlates with the presence of coherent
      quasiparticles within the layers.

PMID- 12050660
TI  - Measurement of a confinement induced neutron phase.
AB  - Particle physicists see neutrons as tiny massive particles with a confinement
      radius of about 0.7 fm and a distinct internal quark gluon structure. In quantum
      mechanics, neutrons are described by wave packets whose spatial extent may become
      ten orders of magnitude larger than the confinement radius, and can even reach
      macroscopic dimensions, depending on the degree of monochromaticity. For neutrons
      passing through narrow slits, it has been predicted that quantization of the
      transverse momentum component changes the longitudinal momentum component,
      resulting in a phase shift that should be measurable using interferometric
      methods. Here we use neutron interferometry to measure the phase shift arising
      from lateral confinement of a neutron beam passing through a narrow slit system.
      The phase shift arises mainly from neutrons whose classical trajectories do not
      touch the walls of the slits. In this respect, the non-locality of quantum
      physics is apparent.

PMID- 12050661
TI  - Marine aerosol formation from biogenic iodine emissions.
AB  - The formation of marine aerosols and cloud condensation nuclei--from which marine
      clouds originate--depends ultimately on the availability of new, nanometre-scale
      particles in the marine boundary layer. Because marine aerosols and clouds
      scatter incoming radiation and contribute a cooling effect to the Earth's
      radiation budget, new particle production is important in climate regulation. It
      has been suggested that sulphuric acid derived from the oxidation of dimethyl
      sulphide is responsible for the production of marine aerosols and cloud
      condensation nuclei. It was accordingly proposed that algae producing dimethyl
      sulphide play a role in climate regulation, but this has been difficult to prove
      and, consequently, the processes controlling marine particle formation remains
      largely undetermined. Here, using smog chamber experiments under coastal
      atmospheric conditions, we demonstrate that new particles can form from
      condensable iodine-containing vapours, which are the photolysis products of
      biogenic iodocarbons emitted from marine algae. Moreover, we illustrate, using
      aerosol formation models, that concentrations of condensable iodine-containing
      vapours over the open ocean are sufficient to influence marine particle
      formation. We suggest therefore that marine iodocarbon emissions have a
      potentially significant effect on global radiative forcing.

PMID- 12050662
TI  - Biodiversity as a barrier to ecological invasion.
AB  - Biological invasions are a pervasive and costly environmental problem that has
      been the focus of intense management and research activities over the past half
      century. Yet accurate predictions of community susceptibility to invasion remain
      elusive. The diversity resistance hypothesis, which argues that diverse
      communities are highly competitive and readily resist invasion, is supported by
      both theory and experimental studies conducted at small spatial scales. However,
      there is also convincing evidence that the relationship between the diversity of
      native and invading species is positive when measured at regional scales.
      Although this latter relationship may arise from extrinsic factors, such as
      resource heterogeneity, that covary with diversity of native and invading species
      at large scales, the mechanisms conferring greater invasion resistance to diverse
      communities at local scales remain unknown. Using neighbourhood analyses, a
      technique from plant competition studies, we show here that species diversity in
      small experimental grassland plots enhances invasion resistance by increasing
      crowding and species richness in localized plant neighbourhoods. Both the
      establishment (number of invaders) and success (proportion of invaders that are
      large) of invading plants are reduced. These results suggest that local
      biodiversity represents an important line of defence against the spread of
      invaders.

PMID- 12050663
TI  - Plant biomarkers in aerosols record isotopic discrimination of terrestrial
      photosynthesis.
AB  - Carbon uptake by the oceans and by the terrestrial biosphere can be partitioned
      using changes in the (12)C/(13)C isotopic ratio (delta(13)C) of atmospheric
      carbon dioxide, because terrestrial photosynthesis strongly discriminates against
      (13)CO(2), whereas ocean uptake does not. This approach depends on accurate
      estimates of the carbon isotopic discrimination of terrestrial photosynthesis
      (Delta; ref. 5) at large regional scales, yet terrestrial ecosystem heterogeneity
      makes such estimates problematic. Here we show that ablated plant wax compounds
      in continental air masses can be used to estimate Delta over large spatial scales
      and at less than monthly temporal resolution. We measured plant waxes in
      continental air masses advected to Bermuda, which are mainly of North American
      origin, and used the wax isotopic composition to estimate Delta simply. Our
      estimates indicate a large (5 6 per thousand) seasonal variation in Delta of the
      temperate North American biosphere, with maximum discrimination occurring in late
      spring, coincident with the onset of production. We suggest that the observed
      seasonality arises from several factors, including seasonal shifts in the
      proportions of production by C(3) and C(4) plants, and environmentally controlled
      adjustments in the photosynthetic discrimination of C(3)-plant-dominated
      ecosystems.

PMID- 12050664
TI  - Host-induced epidemic spread of the cholera bacterium.
AB  - The factors that enhance the transmission of pathogens during epidemic spread are
      ill defined. Water-borne spread of the diarrhoeal disease cholera occurs rapidly
      in nature, whereas infection of human volunteers with bacteria grown in vitro is
      difficult in the absence of stomach acid buffering. It is unclear, however,
      whether stomach acidity is a principal factor contributing to epidemic spread.
      Here we report that characterization of Vibrio cholerae from human stools
      supports a model whereby human colonization creates a hyperinfectious bacterial
      state that is maintained after dissemination and that may contribute to epidemic
      spread of cholera. Transcriptional profiling of V. cholerae from stool samples
      revealed a unique physiological and behavioural state characterized by high
      expression levels of genes required for nutrient acquisition and motility, and
      low expression levels of genes required for bacterial chemotaxis.

PMID- 12050665
TI  - Origin of GABAergic neurons in the human neocortex.
AB  - The mammalian neocortex contains two major classes of neurons, projection and
      local circuit neurons. Projection neurons contain the excitatory neurotransmitter
      glutamate, while local circuit neurons are inhibitory, containing GABA. The
      complex function of neocortical circuitry depends on the number and diversity of
      GABAergic (gamma-aminobutyric-acid-releasing) local circuit neurons. Using
      retroviral labelling in organotypic slice cultures of the embryonic human
      forebrain, we demonstrate the existence of two distinct lineages of neocortical
      GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors,
      represents 65% of neocortical GABAergic neurons in humans, and originates from
      Mash1-expressing progenitors of the neocortical ventricular and subventricular
      zone of the dorsal forebrain. The second lineage, characterized by the expression
      of Dlx1/2 but not Mash1, forms around 35% of the GABAergic neurons and originates
      from the ganglionic eminence of the ventral forebrain. We suggest that
      modifications in the expression pattern of transcription factors in the forebrain
      may underlie species-specific programmes for the generation of neocortical local
      circuit neurons and that distinct lineages of cortical interneurons may be
      differentially affected in genetic and acquired diseases of the human brain.

PMID- 12050666
TI  - Regulation of AMPA receptor lateral movements.
AB  - An essential feature in the modulation of the efficacy of synaptic transmission
      is rapid changes in the number of AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazole propionic acid) receptors at post-synaptic sites on neurons. Regulation
      of receptor endo- and exocytosis has been shown to be involved in this process.
      Whether regulated lateral diffusion of receptors in the plasma membrane also
      participates in receptor exchange to and from post-synaptic sites remains
      unknown. We analysed the lateral mobility of native AMPA receptors containing the
      glutamate receptor subunit GluR2 in rat cultured hippocampal neurons, using
      single-particle tracking and video microscopy. Here we show that AMPA receptors
      alternate within seconds between rapid diffusive and stationary behaviour. During
      maturation of neurons, stationary periods increase in frequency and length, often
      in spatial correlation with synaptic sites. Raising intracellular calcium, a
      central element in synaptic plasticity, triggers rapid receptor immobilization
      and local accumulation on the neuronal surface. We suggest that calcium influx
      prevents AMPA receptors from diffusing, and that lateral receptor diffusion to
      and from synaptic sites acts in the rapid and controlled regulation of receptor
      numbers at synapses.

PMID- 12050667
TI  - Annexin II light chain regulates sensory neuron-specific sodium channel
      expression.
AB  - The tetrodotoxin-resistant sodium channel Na(V)1.8/SNS is expressed exclusively
      in sensory neurons and appears to have an important role in pain pathways. Unlike
      other sodium channels, Na(V)1.8 is poorly expressed in cell lines even in the
      presence of accessory beta-subunits. Here we identify annexin II light chain
      (p11) as a regulatory factor that facilitates the expression of Na(V)1.8. p11
      binds directly to the amino terminus of Na(V)1.8 and promotes the translocation
      of Na(V)1.8 to the plasma membrane, producing functional channels. The endogenous
      Na(V)1.8 current in sensory neurons is inhibited by antisense downregulation of
      p11 expression. Because direct association with p11 is required for functional
      expression of Na(V)1.8, disrupting this interaction may be a useful new approach
      to downregulating Na(V)1.8 and effecting analgesia.

PMID- 12050668
TI  - Filamentous phage integration requires the host recombinases XerC and XerD.
AB  - Many bacteriophages and animal viruses integrate their genomes into the
      chromosomal DNA of their hosts as a method of promoting vertical transmission.
      Phages that integrate in a site-specific fashion encode an integrase enzyme that
      catalyses recombination between the phage and host genomes. CTX phi is a
      filamentous bacteriophage that contains the genes encoding cholera toxin, the
      principal virulence factor of the diarrhoea-causing Gram-negative bacterium
      Vibrio cholerae. CTX phi integrates into the V. cholerae genome in a site
      specific manner; however, the approximately 6.9-kilobase (kb) CTX phi genome does
      not encode any protein with significant homology to known recombinases. Here we
      report that XerC and XerD, two chromosome-encoded recombinases that ordinarily
      function to resolve chromosome dimers at the dif recombination site, are
      essential for CTX phi integration into the V. cholerae genome. The CTX phi
      integration site was found to overlap with the dif site of the larger of the two
      V. cholerae chromosomes. Examination of sequences of the integration sites of
      other filamentous phages indicates that the XerCD recombinases also mediate the
      integration of these phage genomes at dif-like sites in various bacterial
      species.

PMID- 12050669
TI  - A conserved RNA-binding protein controls germline stem cells in Caenorhabditis
      elegans.
AB  - Germline stem cells are defined by their unique ability to generate more of
      themselves as well as differentiated gametes. The molecular mechanisms
      controlling the decision between self-renewal and differentiation are central
      unsolved problems in developmental biology with potentially broad medical
      implications. In Caenorhabditis elegans, germline stem cells are controlled by
      the somatic distal tip cell. FBF-1 and FBF-2, two nearly identical proteins,
      which together are called FBF ('fem-3 mRNA binding factor'), were originally
      discovered as regulators of germline sex determination. Here we report that FBF
      also controls germline stem cells: in an fbf-1 fbf-2 double mutant, germline
      proliferation is initially normal, but stem cells are not maintained. We suggest
      that FBF controls germline stem cells, at least in part, by repressing gld-1,
      which itself promotes commitment to the meiotic cell cycle. FBF belongs to the
      PUF family ('Pumilio and FBF') of RNA-binding proteins. Pumilio controls germline
      stem cells in Drosophila females, and, in lower eukaryotes, PUF proteins promote
      continued mitoses. We suggest that regulation by PUF proteins may be an ancient
      and widespread mechanism for control of stem cells.

PMID- 12050670
TI  - Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling.
AB  - The Wnt family of secreted glycoproteins mediate cell cell interactions during
      cell growth and differentiation in both embryos and adults. Canonical Wnt
      signalling by way of the beta-catenin pathway is transduced by two receptor
      families. Frizzled proteins and lipoprotein-receptor-related proteins 5 and 6
      (LRP5/6) bind Wnts and transmit their signal by stabilizing intracellular beta
      catenin. Wnt/beta-catenin signalling is inhibited by the secreted protein
      Dickkopf1 (Dkk1), a member of a multigene family, which induces head formation in
      amphibian embryos. Dkk1 has been shown to inhibit Wnt signalling by binding to
      and antagonizing LRP5/6. Here we show that the transmembrane proteins Kremen1 and
      Kremen2 are high-affinity Dkk1 receptors that functionally cooperate with Dkk1 to
      block Wnt/beta-catenin signalling. Kremen2 forms a ternary complex with Dkk1 and
      LRP6, and induces rapid endocytosis and removal of the Wnt receptor LRP6 from the
      plasma membrane. The results indicate that Kremen1 and Kremen2 are components of
      a membrane complex modulating canonical Wnt signalling through LRP6 in
      vertebrates.

PMID- 12050671
TI  - New components of the spliced leader RNP required for nematode trans-splicing.
AB  - Pre-messenger-RNA maturation in nematodes and in several other lower eukaryotic
      phyla involves spliced leader (SL) addition trans-splicing. In this unusual RNA
      processing reaction, a short common 5' exon, the SL, is affixed to the 5'-most
      exon of multiple pre-mRNAs. The nematode SL is derived from a trans-splicing
      specific approximately 100-nucleotide RNA (SL RNA) that bears striking
      similarities to the cis-spliceosomal U small nuclear RNAs U1, U2, U4 and U5 (refs
      3, 4); for example, the SL RNA functions only if it is assembled into an Sm small
      nuclear ribonucleoprotein (snRNP). Here we have purified and characterized the SL
      RNP and show that it contains two proteins (relative molecular masses 175,000 and
      30,000 (M(r) 175K and 30K)) in addition to core Sm proteins. Immunodepletion and
      reconstitution with recombinant proteins demonstrates that both proteins are
      essential for SL trans-splicing; however, neither protein is required either for
      conventional cis-splicing or for bimolecular (trans-) splicing of fragmented cis
      constructs. The M(r) 175K and 30K SL RNP proteins are the first factors
      identified that are involved uniquely in SL trans-splicing. Several lines of
      evidence indicate that the SL RNP proteins function by participating in a trans
      splicing specific network of protein protein interactions analogous to the U1
      snRNP SF1/BBP U2AF complex that comprises the cross-intron bridge in cis
      splicing.

PMID- 12050673
TI  - Structural basis for the recognition of hydroxyproline in HIF-1 alpha by pVHL.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that controls
      cellular and systemic homeostatic responses to oxygen availability. HIF-1 alpha
      is the oxygen-regulated subunit of HIF-1, an alpha beta heterodimeric complex.
      HIF-1 alpha is stable in hypoxia, but in the presence of oxygen it is targeted
      for proteasomal degradation by the ubiquitination complex pVHL, the protein of
      the von Hippel Lindau (VHL) tumour suppressor gene and a component of an E3
      ubiquitin ligase complex. Capture of HIF-1 alpha by pVHL is regulated by
      hydroxylation of specific prolyl residues in two functionally independent regions
      of HIF-1 alpha. The crystal structure of a hydroxylated HIF-1 alpha peptide bound
      to VCB (pVHL, elongins C and B) and solution binding assays reveal a single,
      conserved hydroxyproline-binding pocket in pVHL. Optimized hydrogen bonding to
      the buried hydroxyprolyl group confers precise discrimination between
      hydroxylated and unmodified prolyl residues. This mechanism provides a new focus
      for development of therapeutic agents to modulate cellular responses to hypoxia.

PMID- 12050674
TI  - Structure of the SRP19 RNA complex and implications for signal recognition
      particle assembly.
AB  - The signal recognition particle (SRP) is a phylogenetically conserved
      ribonucleoprotein. It associates with ribosomes to mediate co-translational
      targeting of membrane and secretory proteins to biological membranes. In
      mammalian cells, the SRP consists of a 7S RNA and six protein components. The S
      domain of SRP comprises the 7S.S part of RNA bound to SRP19, SRP54 and the
      SRP68/72 heterodimer; SRP54 has the main role in recognizing signal sequences of
      nascent polypeptide chains and docking SRP to its receptor. During assembly of
      the SRP, binding of SRP19 precedes and promotes the association of SRP54 (refs 4,
      5). Here we report the crystal structure at 2.3 A resolution of the complex
      formed between 7S.S RNA and SRP19 in the archaeon Methanococcus jannaschii. SRP19
      bridges the tips of helices 6 and 8 of 7S.S RNA by forming an extensive network
      of direct protein RNA interactions. Helices 6 and 8 pack side by side; tertiary
      RNA interactions, which also involve the strictly conserved tetraloop bases,
      stabilize helix 8 in a conformation competent for SRP54 binding. The structure
      explains the role of SRP19 and provides a molecular framework for SRP54 binding
      and SRP assembly in Eukarya and Archaea.

PMID- 12050675
TI  - Crystal structure of parallel quadruplexes from human telomeric DNA.
AB  - Telomeric ends of chromosomes, which comprise noncoding repeat sequences of
      guanine-rich DNA, are fundamental in protecting the cell from recombination and
      degradation. Disruption of telomere maintenance leads to eventual cell death,
      which can be exploited for therapeutic intervention in cancer. Telomeric DNA
      sequences can form four-stranded (quadruplex) structures, which may be involved
      in the structure of telomere ends. Here we describe the crystal structure of a
      quadruplex formed from four consecutive human telomeric DNA repeats and grown at
      a K(+) concentration that approximates its intracellular concentration. K(+) ions
      are observed in the structure. The folding and appearance of the DNA in this
      intramolecular quadruplex is fundamentally different from the published Na(+)
      containing quadruplex structures. All four DNA strands are parallel, with the
      three linking trinucleotide loops positioned on the exterior of the quadruplex
      core, in a propeller-like arrangement. The adenine in each TTA linking
      trinucleotide loop is swung back so that it intercalates between the two
      thymines. This DNA structure suggests a straightforward path for telomere folding
      and unfolding, as well as ways in which it can recognize telomere-associated
      proteins.

PMID- 12050676
TI  - [Gene expression profiles in the diagnosis and prognosis of cancer].
AB  - DNA-microarray technology can be used to assess the expression of several
      thousands of genes at the same time. The identification of the gene expression
      profiles may help to better characterize human cancer. These studies may reveal
      subclasses of tumor types with similar histopathologic profile but different
      clinical courses.Furthermore,such studies could help to define therapeutic
      sensitivity and to estimate prognosis of various cancers. Identification of gene
      expression profiles of cancer can identify new therapeutic targets or cancer
      susceptibility genes. The DNA-microarray technology may write a new chapter in
      molecular oncology.

PMID- 12050677
TI  - [HER-2 diagnostics].
AB  - HER-2 (c-erbB2, neu) receptor is the molecular marker of ductal breast cancer
      although it is verexpressed in other adenocarcinoma as well (e.g.endometrial,
      colorectal and lung cancers). The increased receptor expression is most
      frequently (90-97%) due to gene amplification. Detection of the overexpression of
      HER-2 helps to determine prognosis, to predict chemoresistance and to select for
      Herceptin therapy. HER-2 overexpression can be estimated either by
      immunohistochemistry or by fluorescent in situ hybridisation (FISH).
      Standardization of the immunohistochemical HER-2 tests is the best in HercepTest
      DAKO), however, the frequent 2+level requires complementary FISH test to verify
      gene amplification. This combination is not necessary at low (0-1+) or high (3+)
      level of immunohistochemical reactions, because the correlation with gene
      amplification status is acceptably high. Recently several new anti-HER-2
      antibodies have been introduced into HER-2 diagnostics in various countries.
      According to our experiences we recommend to combine rationally the
      immunohistochemistry and FISH techniques to determine the HER-2 status in breast
      cancer.

PMID- 12050679
TI  - [FISH diagnostics].
AB  - For over two decades banding has remained the "gold standard" of cytogenetic
      analysis, providing the first genome-wide screen for abnormalities. However,
      conventional cytogenetic banding techniques are limited to the detection of
      rearrangements involving more than 2 Mb of DNA. In addition,the identification of
      de novo unbalanced chromosome rearrangements provides a particular challenge for
      chromosome banding to decipher. In recent years a number of techniques based on
      FISH have evolved, all of which complement the conventional banding approaches
      and which have steadily increased the accuracy of cytogenetic diagnosis. FISH is
      now the method of choice because of the increased sensitivity, and speed with
      which it can be applied to a variety of cellular targets. In this article we try
      to highlight the technical aspects of FISH and the practical application of this
      technique on different tumors (soft tissue tumors, breast carcinomas, renal cell
      carcinomas, bladder tumors and germ cell tumors).

PMID- 12050678
TI  - [The molecular diagnostics of viruses].
AB  - For many years data of cancer research indicated that viruses can cause cancer.
      Virus infections induce cancer by different mechanisms. To predict the
      significance of a viral DNA fragment in human cells we have to be aware of the
      changes the particular virus is able to induce there.However, no matter which
      mechanisms of viral carcinogenesis are utilized, generally other factors
      (environmental, chemical, immunodeficiency, etc.) are also needed to induce
      invasive cancer in human. Before the introduction of nucleic acid based detection
      technique virus identification was a long and cumbersome process. This has been
      eliminated by the invention of recombinant gene technology and polymerase chain
      reaction. Virus nucleic acid can be detected without amplification using
      Southern, Northern and in situ hybridization. Techniques for target (polymerase
      chain reaction)or signal (hybrid capture, tyramine) amplification improved the
      sensitivity of detection. In the meantime, for the successful use of the arsenal
      of new methods we have to consider the characteristic feature of molecular virus
      research. A major achievement of molecular virus detection is that it proved the
      pathological significance of viruses in human cancers even in those where this
      was not expected. Hopefully these informations will increase the effort for
      elimination of oncogene virus infections.

PMID- 12050680
TI  - [Causal association between human papilloma virus infection and head and neck and
      esophageal squamous cell carcinoma].
AB  - HPVs commonly cause proliferative lesions of squamous epithelium, and infection
      with certain HPV types carries a high risk of malignant transformation. We used
      molecular techniques to detect and type HPV in papillomas and carcinomas in the
      oral cavity and esophagus. DNA was extracted from 150 fresh or paraffin embedded
      biopsy specimens, and analyzed for HPV by PCR with 15 sets of consensus primers
      directed to conserved regions of L1 gene, three sets of HPV16E6 primers (specific
      for the HPV 16 prototype and L83V variant), and sets of primers specific for the
      E6 gene of other mucosa type HPVs including HPV 6, 11, 16, 18, 52, 58, 66 and 73.
      Overall, HPV sequences were detected in 61 of 150 specimens. HPV DNA sequences
      were detected in 16/32 specimens in the oropharyngeal region, in 13/36 specimens
      in larynx and 32/82 specimens in esophagus. Papillomas contained only the
      episomal form of HPV 16. In the esophagus, the most common type was HPV 73. In
      all specimens examined, HPV 6/11 (4/150), HPV 16 (23/150), HPV 35 (1/150), HPV 45
      (1/150), HPV 54 (1/150), HPV 58 (1/150), HPV 61 (1/150), HPV 66 (1/150), HPV 68
      (2/150), HPV 70 (3/150), HPV 72 (1/150), HPV 73 (16/150), double HPV infection
      (2/150), and unidentified HPV type (4/150) was detected. Interestingly, HPV was
      found in all verrucous carcinomas and in 18/22 basaloid squamous cell carcinomas.
      HPV16E6 T350G mutant were observed only in two of eight carcinomas. Using
      correspondence analysis, a segregation of specific virus types in specific
      clinico-pathologic lesions (verrucous carcinoma and basaloid squamous cell
      carcinoma) was proved. It was shown that the relative rates of the HPV positive
      tumors were significantly higher in women than in men. The synergic action of
      mucosal irritation and HPV infection may be necessary for the development of the
      papillomas and the specific types of carcinomas in the oral cavity and in the
      esophagus.

PMID- 12050681
TI  - [Detection of n-myc gene amplification in neuroblastoma using polymerase chain
      reaction based methods].
AB  - We have used semiquantitative and real-time quantitative PCRs to detect n-myc
      gene-amplification in 21 frozen neuroblastoma biopsies and IMR 32 cell line in
      order to predict biological behaviour of the tumors. Two primer pairs were used
      in the semiquantitative method to co-amplify a 520-bp fragment of the beta 
      globin gene -used as a single copy reference standard -and a 258-bp fragment of
      the n-myc gene. After 30 cycles the PCR products were electrophoresed through an
      agarose gel and were compared to each other with use of a gel-densitometer. Real
      time quantitative analysis was performed in a LightCycler instrument. A single
      primer pair was used to amplify a 120-bp fragment of the n-myc oncogene and a
      LC640-labelled fluorescent probe pair to detect the product. Calibration curve,
      which was set up from a serial dilution including samples with 1, 2, 10, 13, 25
      fold n-myc oncogene amplification, was employed for quantitative analysis.
      Semiquantitative method did not show distinct difference between tumor groups
      with no amplification and less than 10-fold amplification, while quantitative
      LightCycler analysis was able to detect even 2-fold amplification. In situ PCRs
      were performed in two cases of differentiated tumor samples which contained n-myc
      amplification. We used biotinylated ATP labelling and the same primer pair as for
      the LightCycler analysis.In both cases differentiated cell forms did not show n
      myc gene amplification, while considerable amplification was detected in the
      neuroblasts.

PMID- 12050683
TI  - [Chemoprevention of breast cancer - with special interest of tamoxifen]
AB  - The adjuvant use of tamoxifen confers a survival advantage for patients with node
      positive and node-negative breast cancer and demonstrated benefit when used alone
      or in combination with chemotherapy to treat advanced breast cancer.Tamoxifen
      prevents induced mammary cancer in rats, decreases the contralateral breast
      cancer incidence in humans, and its safety record in clinical practice is
      excellent. This finding led to the concept that the drug might play role in
      breast cancer prevention. In 1986 at the Royal Marsden Hospital a small pilot
      study was started, which would serve as a feasibility assessment for a larger
      trial to determine if tamoxifen prevents breast cancer. The trial shows no
      effect, because the study is too small for accurate results. Similarly, in
      another tamoxifen prevention study performed in Italy, the incidence of breast
      cancer did not differ between groups of tamoxifen and placebo. The negative
      finding of the study is readily explained by the relatively low risk of breast
      cancer development in the study population, the high drop-out rate and the small
      number of women who completed 5 years of treatment. In the NSABP P-1 prevention
      trial tamoxifen reduced the risk of invasive breast cancer by 49% and of
      noninvasive breast cancer by 50% in the increased risk population of 13.388
      healthy women. The article summarizes the recent theoretical and practical data
      of the chemoprevention of breast cancer.

PMID- 12050682
TI  - [Principles of radiotherapy of non-small cell lung cancer].
AB  - The long-term survival probability for Hungarian lung cancer patients is 10%
      worse than the best results published in the most highly developed countries (the
      mean 5-year survival probability in Hungary is 5%, in contrast with the 15%
      survival probability in the USA). On the basis of the international
      recommendations and personal experience, an attempt was made to formulate the
      guidelines for radiotherapy as one of the fundamental non-small cell lung cancer
      (NSCLC) treatment modalities for national use. An expert panel was set up
      comprising physicians from 6 radiotherapeutic centers (the National Institute of
      Oncology / Semmelweis University, Budapest; the Beth Israel Medical Center, New
      York; the University of Kaposvar; the University of Essen; the University of
      Debrecen; and the County Hospital of Gyula). Experts in two important medical
      fields closely related to radiotherapy (surgery and diagnostic imaging) were also
      engaged in the elaboration of the manuscript. Discussion of the most important
      principles of the radiotherapy and an overview of the prognostic factors was
      followed by a critical analysis of the protocols applied in the radiotherapy of
      Hungarian NSCLC patients during recent decades. The new guidelines suggested for
      the radiotherapy of NSCLC are presented separately for the postoperative period,
      marginally resectable tumors, and the aggressive or non-aggressive radiotherapy
      of inoperable tumors. Detailed accounts are given of the techniques of external
      irradiation and brachytherapy, and of the acute and late radiation-induced damage
      of normal tissues. The authors believe that this document may be instrumental in
      improving the survival index of Hungarian NSCLC patients in the near future.

PMID- 12050684
TI  - [The effect of tumour bed boost on local control after breast conserving surgery.
      First results of the randomized boost trial of the National Institute of
      Oncology]
AB  - PURPOSE: To evaluate the effect of tumour bed boost on local tumour control (LTC)
      after breast conserving surgery in a prospective study. METHODS: Between 1995 and
      1998, 207 women with early invasive breast cancer who underwent conservative
      operation were treated by 50 Gy irradiation to the whole breast and then randomly
      assigned to receive either no further radiotherapy (n=103) or a boost to the
      tumour bed (n=104) with either 16 Gy electron (n=52) or 12-14.25 Gy high dose
      rate brachytherapy (n=52). RESULTS: At a median follow-up of 4.25 years the crude
      rate of local recurrence was 6.7% with and 13.6% without boost. The respective
      rates of tumour bed relapse were 3.8% vs. 10.7%. The 4 year probability of LTC,
      relapse-free survival and breast cancer-specific survival was 94.2% vs. 85.1%
      (p=0.1176), 82.3% vs. 67.2% (p=0.0438) and 84.8% vs. 90.9% (p=0.1111),
      respectively, in favour of the boost group. Systemic treatments had no
      significant impact on LTC (88.9% with and 89.6% without systemic treatment,
      p=0.8858). CONCLUSION: Tumour bed boost decreased the incidence of local and
      tumor bed relapses with a reduction of 50% and 64%, respectively. Relapse-free
      survival was improved significantly with boost. However, the influence of boost
      treatment on breast cancer-specific survival should be tested in further studies.
      In spite of the higher incidence of late radiation side effects in the boost arm,
      boost dose is strongly recommended for patients at high risk for local
      recurrence. The final results of the EORTC trial and other ongoing studies will
      help to clarify the indication of boost dose according to prognostic subgroups.

PMID- 12050685
TI  - [Ovarian carcinoma of low malignant potential treated at the 1(st) Department of
      Obstetrics and Gynecology Semmelweis University Faculty of Medicine, between 1990
      and 2000]
AB  - The authors analyzed the epidemiologic and histological characteristics and the
      management of ovarian carcinoma of low malignant potential (LMP) at a university
      hospital between 1990 and 2000. The authors carried out a retrospective study
      reviewing hospital charts. Based on the records experience with 29 such tumors is
      peresented. Of these 20 (74%) were of the serous variety, 7 (26%) were mucinous.
      LMP tumors accounted for 16% of proliferating epithelial ovarian tumors. They
      occured at a mean age of 45 years. The LMP tumors were bilateral in 12% of the
      cases. The majority of patients (87%) with LMP tumors presented with early stage
      disease. Tumor markers such as CA-125 were not always elevated as in invasive
      ovarian carcinoma. Laboratory investigations have not demonstrated that these
      tumors represent an intermediate step between benign ovarian tumors and
      carcinoma. The recommended therapy is surgical, consisting of total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, and tumor
      debulking. Conservative surgery consisting of unilateral salpingo-oophorectomy is
      considered to be an appropriate treatment for young women with early stage LMP
      ovarian tumors who wish to retain their fertility potential. 50 percent of women
      who underwent conservative surgery subsequently conceived in this study. There
      were no recurrences in the study group, so the authors conclude that the long
      term outcome of LMP tumors is extremely favorable.

PMID- 12050686
TI  - [Treatment results of childhood Hodgkin's lymphoma in Hungary]
AB  - Lymphomas are the third most frequent malignancies in childhood. The Hungarian
      Pediatric Oncology Group was founded in 1971, and since then the same
      chemotherapeutic protocols have been used in the whole country. In this study we
      analyzed the data of childhood Hodgkin's lymphoma in Hungary in the last 11 years
      (1988-1998). We also compared our results with the international (German) data.
      The incidence of Hodgkin's lymphoma (0-15 years) was 7.1/1,000,000 child/year
      (the same for non-Hodgkin's lymphoma was 7.5/1,000,000/year); 5.5% of all
      pediatric malignancies in Hungary). The patients were treated according to the
      German DAL-HD-82 and 90 protocols. The therapy consisted of 2-6 cytostatic
      blocks, depending on the stage, followed by involved field irradiation. The
      overall survival was 94.7+/-2.0% at 5 years and 91.9+/-2.7% at 10 years. These
      results are very similar to the German data: 94% at 5 years and 93% at 10 years.
      The good results are due to the well organised network and the uniformed
      treatment. The results may be ameliorated by using autologous bone marrow
      transplantation.

PMID- 12050687
TI  - [The role of irinotecan in the treatment of advanced colorectal cancer]
AB  - PURPOSE: The purpose of the study was the evaluation of efficacy and the side
      effects of irinotecan in treatment of advanced colorectal cancer. METHODS: The
      authors presented their experiences with irinotecan in the treatment of 10
      patients suffering from advanced colorectal cancer. The dose of irinotecan was
      350 mg/m(2) every 21 days. Seven out of ten patients have taken oral
      fluoroquinolon to investigate its effect on the incidence of febrile episodes in
      case of febrile neutropenia. Three out of ten patients did not receive any
      antibiotic. The authors have examined the efficacy and safety of the treatment.
      RESULTS: One complete remission was obtained. Authors describe the observed side
      effects and the administered supportive care against serious complications.
      DISCUSSION: Serious diarrhoea has not been found in case of these 10 patients.
      The diarrhoea caused by irinotecan can be stopped by loperamide. The authors give
      accounts of early and following results.

PMID- 12050688
TI  - [Radiotherapy of childhood brain stem tumours]
AB  - STUDY OBJECTIVE: Description and evaluation of radiotherapy of inoperable brain
      stem tumours. Possibilities of improving therapeutic results. MATERIALS AND
      METHODS: Between 1987 and 2000 43 patients (23 boys and 20 girls, mean age 8.5+/
      4.4 years) with brain stem tumours were treated with 6 MV and 9 MV X-ray. The
      doses administered ranged from 30 to 66 Gy; mean 50.41+/-7.67 Gy. Treatment in
      each case was performed according to CT- and /or MR-based radiotherapy plan.
      Since 2000 3D conformal radiotherapy plans have been prepared by using image
      fusion. RESULTS: All patients were followed. The mean follow-up period was 19.4
      months (range: 1 to 112 months). For survival statistics the 2 to 3-year overall
      and symptom-free survivals were taken into account, the former ones in the
      function of tumour localisations. The gender of children did not affect the
      survival (p>0.74). No significant difference was found as to survival in the
      function of tumour localisation either (p>0.87). CONCLUSION: According to the
      literature data the results expected were not achieved by hyperfractionation and
      by delivering an overall focal dose of 72 to 78 Gy. Results can be improved by
      precise patient fixation and the routine application of 3D conformal radiotherapy
      plans prepared by CT- and MR-based image fusion. These together can result the
      correctly reproducible patient fixation, the homogenous radiation delivery in the
      target volume and the reduction of injury in the surrounding tissues. Irradiation
      should be performed also in histologically not verified tumours since a 24.6
      month transitory improvement could be achieved in 60.5% of our patients.

PMID- 12050689
TI  - [Hypothyroidism in Hodgkin's disease patients]
AB  - PURPOSE: Study of thyroid function in Hodgkin's disease patients in complete
      remission. PATIENTS AND METHODS: We examined the thyroid function of 160
      Hodgkin's disease patients in complete remission for at least one year, and
      determined the values of supersensitive thyroid stimulating hormone (sTSH), free
      T4 (fT4), free T3 (fT3) hormones. RESULTS: Normal values were observed in 117
      patients, subclinical change (only elevated sTSH) in 28 patients, clinical
      hypothyroidism in 14 patients (also low fT4 and/or fT3), hyperthyroidism
      (Basedow's disease) in one patient. Hypothyroidism was one and a half times more
      frequent in females than in males. The normal and low thyroid function group did
      not differ from each other in mean age, histological subtypes, disease stage,
      general symptoms, and whether lymphangiography was performed. Hypothyroidism was
      more frequent in patients who had undergone mantle or neck radiotherapy. The
      onset of thyroid gland underfunction was more pronounced from six years after
      neck radiotherapy. The thyroid disease could be controlled using a daily dose of
      25-225 mg levothyroxin. CONCLUSIONS: During the care of Hodgkin's disease
      patients routine examination of the thyroid function is important for the early
      recognition and prevention of treatment related late complications. On the other
      hand in treatment planning phase more attention should be paid to thyroid gland
      protection when neck radiotherapy is used.

PMID- 12050690
TI  - [Bilateral germ cell testicular tumors]
AB  - PURPOSE: To study the clinical characteristics of bilateral testicular tumors in
      the cisplatin era. PATIENTS AND METHODS: Between November 1988 and November 1998
      2386 testicular cancer patients were treated in our Department and 72 bilateral
      germ cell testicular cancer patients were retrospectively explored (3%). The
      incidence, the clinical and histological characteristics and, in the case of
      asynchronous tumor, the interval between the two tumors were analyzed. RESULTS:
      During the 10 years 19 synchronous (26.4%) and 53 asynchronous bilateral germ
      cell testicular cancers (73.6%) were treated. The incidence of bilateral
      synchronous seminoma was 68.4%. Among the asynchronous tumors 9 concordant
      seminomas and 9 concordant nonseminomas were detected. In the first, second and
      third 5-year follow-up period 39.6, 30.2, and 28.2% of asynchronous tumors were
      diagnosed. The incidence of seminoma after the first castration in the 5, 10 and
      15 years was 19, 37.5, and 60%, respectively. The overall survival rates of
      synchronous and asynchronous testicular cancer were 84 and 93%. In cases of
      asynchronous tumor the prevalence of stage I cancer was significantly greater in
      a regularly controlled population (p=0.014) than in the not regularly followed
      population, but the survival rate was good in both groups. Nonseminoma showed up
      earlier as first and second tumor than seminoma (p=0.05, p=0.045). The interval
      between the two asynchronous tumors was shorter in the case of nonseminoma than
      in the case of seminoma (p=0.002). CONCLUSION: The prognosis of bilateral germ
      cell testicular cancer is good because of the high incidence rate of seminoma and
      the effective treatment. With regular follow-up the early diagnosis of second
      testicular tumors is probable. The interval between the tumors depends on the
      patients' age and the histology of the second tumor, in the case of seminoma it
      is longer. The effect of the previous treatment on the incidence of seminoma and
      the interval between the two asynchronous tumors requires further investigations.

PMID- 12050691
TI  - [Investigation of oncogene amplification or deletion, and oncoprotein expression
      in papillary thyroid cancer]
AB  - AIM: Assessment of occurrence and possible prognostic significance of c-myc and
      Ha-ras amplification, p53 deletion and overexpression of cyclin D1, p53 and p21
      in papillary thyroid cancer. MATERIALS AND METHODS: Formalin-fixed, paraffin
      embedded tumor tissue from 24 patients were investigated. Dot-blot DNA
      hybridization was used to detect oncogene amplification or deletion. The
      expression of oncoproteins was determined by immunohistochemical method. RESULTS:
      In our samples neither Ha-ras amplification nor p53 deletion were found. Low c
      myc amplification (mean: 2.55) occured in 4 cases (17%). p53 protein was detected
      in 16 samples (66.6%), with p21 expression (chi(2)=7.02, p<0.01) in 6 cases
      (25%). The p53 expression did not influence the tumor fenotype. Cyclin D1
      overexpression was found in 12 cases (50%), it was often associated with p21
      expression (chi2=10.1, p<0.001) and in inverse relation to the tumor lymphocytic
      infiltration (chi(2)=5.35, p<0.05). Increased expression of estrogen receptor was
      shown in 4 cyclin D1 positive samples (17%). CONCLUSIONS: The p53 detected in our
      study is likely not to be mutant protein in all cases because its presence was
      associated with p21 expression that the mutant protein cannot induce and also it
      did not mean more aggressive tumor phenotype. The connection of cyclin D1
      overexpression with the lymphocytic infiltration of the tumor suggests that the
      increased expression of cyclin D1 means poor prognosis. The coexpression of
      cyclin D1 and p21 raises the modulative character of the p21 protein, thought to
      be a tumor suppressor originally, but we find a CDK-independent, estrogen
      receptor mediated effect of cyclin D1 more likely, which has been described in
      breast cancer and is also proved by the coexpression of cyclin D1 and estrogen
      receptor detected here.

PMID- 12050692
TI  - [Tumorus anorexia/cachexia syndrome]
AB  - The clinical importance of tumor-induced cachexia is indicated by the fact that
      two thirds of the cancer patients suffer from it and it plays an outstanding role
      in mortality of the disease. The onset of the tumorous anorexia/cachexia syndrome
      does not depend on tumor burden or the stage of the disease. The syndrome is very
      complex in nature and cannot be reversed by "over-feeding" of the patient. The
      appropriate supply of calories, carbohydrates, proteins and lipids is impossible,
      therefore administration of nutrients which do not cause volume-load for the
      patient is justified. Enteral feeding must be the primary aim in cancer patients
      till the gastrointestinal tract is functioning. To improve appetite and increase
      body weight specific pharmacological intervention may also be necessary.
      Understanding the molecular mechanisms of the development of tumorous
      anorexia/cachexia syndrome opens new ways of treatment.

PMID- 12050693
TI  - [Etiology and treatment of malignancy-associated anaemia]
AB  - Patients with cancer frequently develop anaemia. Various factors, including the
      type of malignancy and the intensity of chemotherapy influence the prevalence of
      anaemia and need of transfusions. Among the numerous causes of its development,
      the most frequent type is cancer anaemia, the so-called "anaemia of chronic
      disorders". Anaemia of chronic disorders is diagnosed when neoplastic disease is
      accompanied by an otherwise unexplained microcytic anaemia with compromised iron
      utilisation and decreased erythropoietin secretion. In 50-70% of patients with
      solid tumors or hematological malignancies, mainly with multiple myeloma and
      malignant lymphomas, transfusion can be avoided, or significantly decreased by
      the use of recombinant erythropoietin. This review provides tools to decide the
      best candidates for this treatment and a guideline to monitor its efficacy.

PMID- 12050694
TI  - [Biological basis of radiochemotherapy]
AB  - The tumor biological and radiobiological aspects, the mechanism of actions and
      general considerations of clinical application of radiochemotherapy are
      discussed. The aims of radiochemotherapy are to prolong the patient's survival by
      improving local tumor control and decreasing distant metastases. The goal of
      radiochemotherapy is to enhance the therapeutic effect of radiation with
      tolerable and controllable local and systemic side effects. The mechanism of
      action of the most frequently used drugs are also discussed.

PMID- 12050695
TI  - [Radio-chemotherapy of locally advanced head and neck cancer, providing tissue
      and organ protection]
AB  - PURPOSE: the study of the effect of Amifostine in reducing acute mucositis,
      xerostomia and late xerostomia emerging in the course of locally advanced head
      and neck cancer radio-chemotherapy. METHODS: Starting in 1999 we have conducted
      radio-chemotherapy treatment on 7 patients with or without Amifostine protection,
      each receiving 60 Gy (2 Gy a day/5 fractions a week) loco-regional irradiation.
      From the first to the fifth day and from the twenty-first to the twenty-fifth day
      prior to irradiation they were given a 70 mg/m(2) Carboplatin treatment. In the
      Amifostine group, on days 1-5 and 21-25 300 mg/m(2) and on days 6-20 and 26-30
      200 mg/m(2) Amifostine therapy was given prior to the radio- and chemotherapy.
      RESULTS: In the course of the trial we did not find any haematologic side
      effects, or side effects directly connected to the Amifostine, which would have
      required suspension of the therapy. In the active phase, mucositis of Grade 1-2
      was detected 1-2 weeks later than in the control group, in contrast to the
      mucositis of Grade 2-3 in the other arm. Global oral discomfort associated with
      acute xerostomia was of Grade 4-6 on a linear scale of ten, compared with Grade 7
      8 on the active line. We had similar results when testing the symptoms directly
      connected with late xerostomia. Unstimulated and stimulated saliva production
      doubled following the Amifostine treatment. CONCLUSION: Despite the small pool of
      patients we have the impression that Amifostine can effectively reduce the
      severity of acute mucositis, xerostomia and late xerostomia.

PMID- 12050696
TI  - [Radiochemotherapy of bladder cancer with/without tissue-organ protection]
AB  - The authors report the results of radiochemotherapy for bladder cancer, both
      advanced and early with a poor prognosis, on the basis of their own material as
      well as based on the literature. More than half of the patients received
      radioprotective madication at the same time. The short follow-up does not allow
      for far-reaching conclusions, but early results and limited complications appear
      hopeful. The authors emphasise that, if indicated, radiochemotherapy can serve as
      an alternative to cystectomy.

PMID- 12050697
TI  - [Electronic portal imaging (EPI) on linear accelerator]
AB  - The EPI has become available recently in the Oncoradiological Centre of Budapest.
      The purpose of this paper is to review the construction and operation of the
      electronic portal imaging devices (EPIDs). The different EPID systems as well the
      EPID technique vs. portal films are compared. The advantages in patient set-up
      and the detection of the set-up errors are discussed. The use of the EPID
      technique in the clinical everyday practice is detailed. Recommendations of the
      set-up error correction for the most often occurring failures is given.

PMID- 12050698
TI  - [Field matching in breast irradiation]
AB  - INTRODUCTION: In this paper the authors have combined different irradiation
      techniques for breast and adjacent supraclavicular lymph nodes. The aim was to
      reduce inhomogeneity in the match-line. METHODS: The CadPlan 6.1.5 three
      dimensional treatment planning system was applied in this study for CT based plan
      using a standard medial and lateral wedged tangential breast portals with the
      adjacent supraclavicular field. Isocenter is placed at depth on the match-line,
      where asymmetric jaws are used to produce non-divergent field edges. The
      tangential fields are shaped using multi-leaf collimator (MLC), by following the
      curvature of the thorax. In this way the cranial vertical match plane is
      maintaned without using the breast board. The prescribed dose was 50 Gy at the
      isocentre. RESULTS: The calculated dose distributions were evaluated in three
      dimension in the match region of supraclavicular field and the two opposing
      tangential fields. This method produces a more uniform dose distribution in the
      target volume and in the match-line. Set-up is fast, this is done without the
      need for table rotation, or vertical cephalad blocks. The average dose to the
      ipsilateral lung is reduced using the IMRT (intensity modulated radiotherapy)
      technique by approximately 10% compared with the conventional technique.
      Furthermore, this new technique has the possibility to improve the field match
      between the tangential fields and the parasternal field, while maintaning the
      field match between the tangential fields and the axillary and supraclavicular
      fields.

PMID- 12050700
TI  - [Radiotherapy of benign disorders]
AB  - The radiation oncologist's primary concern is treatment of patients with
      malignant tumors but sometimes faces on occasion rare, non malignant disorders.
      The scarcity of disease incidence is reflected by the paucity of references for
      these diseases in the literature. This minimal exchange of information may make
      research and analysis difficult, tedious and not easily directed. Even with
      recognition of the risks of late skin injury, carcinogenesis, leukemogenesis and
      genetic damage from all ionizing radiation, radiation therapy also continues to
      be accepted treatment for benign diseases that do not respond to other methods of
      therapy. The purpose of this paper is to provide a short overview of the
      radiotherapy of most frequent benign disorders.

PMID- 12050699
TI  - [Preoperative radiation therapy for rectal cancer. personal experience]
AB  - PURPOSE: Comparison of the effectiveness of preoperative and "sandwich"
      (preoperative and postoperative) radiation therapy in the treatment of midrectum
      and lower rectum carcinoma, based on a prospective clinical trial. MATERIAL AND
      METHOD: Over the period between 1990 and 1997, we treated 115 patients suffering
      from mid-rectum and lower rectum carcinoma at the Budapest Oncoradiological
      Centre, using sandwich therapy (22.5 Gy preoperative-27.5 Gy postoperative) in
      the case of 36 patients and 36 Gy preoperative radiation therapy in the case of
      79 patients with external-beam megavoltage therapy with mostly telecobalt
      radiation and to a smaller number of cases 6 MV energy. The external-beam
      radiation therapy was nearly always applied with a 4-field box technique, and
      radical surgery was performed within 10 days following the preoperative radiation
      treatment. Effectiveness was evaluated in terms of a Log-Rank and Peto-Wilcoxon
      tests and the Kaplan-Meier survival curve. RESULTS: The effectiveness of the
      different therapies was compared in terms of the percentage of local failure and
      the rate of disease-free survival. The results show that when using the
      "sandwich" radiation therapy local failure is expected to occur in 13.8% of all
      cases, compared with 17.7%, when only preoperative radiation therapy is used. In
      terms of five-year disease-free survival, the sandwich therapy seems to be
      better, but for a higher number of years, namely 7.5, the preoperative radiation
      therapy yielded better results. CONCLUSION: In terms of local failure, the
      effectiveness of the preoperative and the "sandwich" radiation therapies for the
      treatment of mid-rectum and lower rectum carcinoma was nearly identical, while
      preoperative radiation therapy provided longer disease-free survival. Further
      trials using multivariation analysis need to be performed to evaluate the two
      types of radiation treatments, taking into account other parameters, such as
      grading, age and lymphatic spread.

PMID- 12050701
TI  - [Radiotherapy of early breast cancer. More than loco-regional tumor control]
AB  - The authors review the value of radiotherapy in the multidisciplinary treatment
      of early (stage 0-II) breast cancer and describe past achievements, current
      scientific evidences and possible future prospects of clinical research. Results
      of randomized studies proved that conservative surgery with radiotherapy is
      equally effective to mastectomy for the treatment of in situ and invasive breast
      cancer, both in terms of local control and overall survival. In the nineties,
      findings of prospective clinical trials indicate that the use of irradiation in
      high-risk patients provides both a significant improvement in loco-regional
      control and survival rate. The magnitude of survival benefit with appropriate
      patient selection and radiotherapy technique is similar to that seen with
      adjuvant systemic therapy. Radiotherapy of early breast cancer is based on level
      I scientific evidences in the vast majority of cases. Remaining controversial
      issues are subjects of several ongoing international and Hungarian prospective
      randomized studies.

PMID- 12050702
TI  - [Spatial differences in mortality and morbidity from cancer of the lip, oral
      cavity and pharynx in Hungary]
AB  - In evaluating the health state of the population one of the most reliable
      parameter is mortality. The development of statistical and spatial analytical
      methods gave a tool for evaluating mortality and morbidity in small areas. GIS
      mapping helps in the assessment of health state of small areas, to investigate
      causal relationship and create plans of intervention. Within the frames of the
      National Environmental Health Action Programme (NEHAP, 1996) a spatial
      statistical information system was elaborated. By the help of this system,
      mortality from cancer of the lip, oral cavity and pharynx (ICD-X.: C00-C14) was
      analysed for 1986-1997 and morbidity for 1997-1999 by computing standardised
      mortality and morbidity ratio. Regions with unfavourable mortality and morbidity
      were defined, statistical significance was tested. After age and gender
      stratification, a cluster analysis was also carried out. An international
      comparison of mortality was done as well. According to our data, mortality - most
      frequent in both sexes according to the international comparison - as well as
      morbidity showed a typical spatial distribution. An excess in mortality and
      morbidity is observable in the central part of the country, as well as in the
      Northern part and in traditional wine producing areas. The spatial accumulation
      of mortality is very similar to that of mortality from chronic liver diseases
      (ICD-X.: K70). In the primary prevention of oral cancer smoking cessation and the
      decrease of alcohol consumption is of great importance. Screening activity of GPs
      and dental doctors is of major importance in secondary prevention.

PMID- 12050703
TI  - [Aetiology and risk factors for oral cancer, with special reference to tobacco
      and alcohol use]
AB  - Animal experiments, in vitro studies of mechanisms, biological plausibility and
      massive epidemiological evidence prove that tobacco-smoked and unsmoked - is the
      major cause of oral cancer in the world. In Hungary today tobacco is mostly
      smoked in cigarettes, the smoking prevalence being amongst the highest in Europe:
      it is no surprise that Hungary has the highest rate of oral cancer in the world
      today. Tobacco use, however, synergises with heavy alcohol use in a dose
      dependent manner, the effect being supermultiplicative: most of the rising
      incidence of oral cancer in Europe is probably due to rising alcohol consumption
      in recent decades in the presence of continuing high levels of tobacco use.
      Smaller roles can be ascribed to inherited predisposition, environmental agents,
      poor diet, infections with viruses and fungi and poor oral hygiene/oral health
      care. The approach to primary prevention is thus clear, and must emphasise
      tobacco avoidance and sensible use of alcohol, together with good nutrition and
      dental care.

PMID- 12050704
TI  - [The hierarchy of approaches to tobacco control]
AB  - Tobacco represents the single most preventable cause of disease and death in the
      world today. Of 260 million male deaths in the developed world between 1950 and
      2000, it is estimated that 50 million will be due to smoking. In the oral and
      craniofacial region tobacco use has been associated with the occurrence of cleft
      palate, periodontal disease and tooth loss, and a variety of soft tissue lesions
      including oral cancer. For example, smoking is estimated to account for 92% of
      cancers of the lip, oral cavity and pharynx. Few studies have examined relative
      efficiency of the many different approaches to tobacco control but, in general,
      legislative approaches such as increasing tobacco taxes and prohibiting
      advertising are most effective and those based on printed educational materials
      and cessation groups, the least effective. In all cases, advice or intervention
      by health care professionals ranked among the most effective non-legislative
      approaches to control. A very wide range of professionally-based interventions
      have been described, including pharmacologic interventions, behavioral approaches
      and group counseling. The dental profession has a unique opportunity to influence
      tobacco use by their patients. Its use is almost always immediately evident to
      the dentist or dental assistant in terms of odor, staining, poor oral hygiene or
      obvious oral disease. There is also a tendency for the length of personal contact
      with the dentist to be greater than with a physician. Guidelines are now
      available that provide the dental professional with advice on the best approaches
      to tobacco control with their patients.

PMID- 12050705
TI  - [Behavioral approaches in tobacco control]
AB  - In most Western societies, there is an abundance of information on what needs to
      be done to control the use of tobacco. This paper presents different strategies
      for addressing tobacco control. Many of the strategies such as increasing taxes,
      increasing control over promotion of tobacco, and the restriction of smoking
      should be made a priority. However, there is still the need to provide help for
      the smoker to quit. The evidence with regards to effective ways of getting
      smokers to quit and the effectiveness of different modalities is reviewed.
      Programs found to be effective include self-help, individual counseling, and
      group counseling. Counseling programs appear to double the effect of success
      compared to no program. Nicotine replacement therapy has been demonstrated to be
      an important adjunct therapy to the behavioral programs. Issues regarding the
      cessation of tobacco by youth need to be addressed distinctively from adult
      cessation. Relapse prevention for both youth and adults needs to become a major
      focus of programs dealing with smokers who want to quit.

PMID- 12050706
TI  - [Reducing children's exposure to environmental tobacco smoke: Evidence from the
      U.S. and implications for Hungary]
AB  - This review summarizes empirical evidence for clinical interventions designed to
      reduce children's residentia environmental tobacco smoke (ETS) exposure.
      Legislation prohibiting ETS exposure in public buildings, especially work
      settings, may decrease ETS exposure in private residences. Media, policy/legal
      regulations, and brief clinical advice require more study to determine their
      effectiveness for decreasing ETS exposure in private residences. Three published
      and two in progress trials found that repeated counseling reduced ETS exposure in
      asthmatic and healthy children from lower through middle class families.
      Dentists, physicans, and other clinicians may be strategic supervisors for
      paraprofessional counseling designed to lower children's ETS exposure in their
      home. Research is needed to determine the cultural tailoring needed to be
      effective in Hungary.

PMID- 12050707
TI  - [Self-destructive behaviour in the Hungarian population]
AB  - In Hungary today the mortality rate of middle aged (55-64 years old) men is
      higher than it was in the 1930s. Within these statistics there are considerable
      socioeconomic differences, the mortality rate of lower secondary or lower
      educated middle aged men is 1.45 times higher than among those with higher
      education. About 40% of these socioeconomic mortality differences can be
      explained by higher prevalence of risk behaviour in lower socioeconomic groups.
      According to the results of our national representative survey conducted in the
      Hungarian population with 12640 persons in 1995, the prevalence of smoking was
      45.5% among men and 26.6% among women. In the populaton younger than 45 years old
      the prevalence of smoking among men was 47.9%, among women 31.9%. Among men there
      is a clear socioeconomic gradient in smoking, in the number of daily cigarettes,
      the quantity of spirit consumption in one occasion, among women this
      socioeconomic gradient is not so obvious. The effectiveness of health promotion
      programmes depends on effective management of the motivational, psychological
      determinants of risk behaviour.

PMID- 12050708
TI  - [Stomato-oncological screening examinations: possibilities for early diagnosis]
AB  - The dramatic increase in the mortality of lip- and oral cancers in Hungary in the
      last decades points to the importance of primary and secondary prevention.
      Stomato-oncological screening examinations belong to the latter category, and
      might represent useful tools in the early diagnosis and treatment of oral
      carcinomas and precancerous lesions. The aim of the paper is to review the
      methods, results and effectivity of stomato-oncological screening examinations in
      Hungary. Between 1962 and 2000 nine screening examinations were performed: one on
      a population sample, one in an industrial setting, four connected to X-ray lung
      screening examinations (one with the help of a mobile unit), one on voluntary
      persons, one on high risk people (homeless), one in general medical practice.
      Among these, in the last five years, in the course of the stomato-oncological
      examination of 17325 individuals, oral carcinoma has been found in 0.12%, and
      oral precanceroses in 2.63%. Although the general dentist is obliged by law to
      perform a stomato-oncological examination on the patients appearing in the
      practice, unfortunately, about 50-to-90% of the population does not visit a
      dentist regularly. The regular examination of these - high risk - groups by the
      help of the above methods, including the help of general medical practitioners is
      highly recommended.

PMID- 12050709
TI  - [Proposal for screening of oral and oropharyngeal cancer in the population at
      risk]
AB  - The aim of our proposal is to suggest selected screening for people, who are the
      most likely candidates for the development of head and neck cancer. The screening
      organized by the family physicians on their own database in collaboration with
      the local dentists or ENT doctors involves examination and health education by
      effective communication and written information about risk of cancer and early
      signs and symptoms of the disease.

PMID- 12050710
TI  - [Exposure or cancer predisposition? Cytogenetic examination of head and neck
      squamous cancer patients]
AB  - Search of different biomarkers is one of the most important demands of the
      national cancer prevention programme. We examined the usefulness of bleomycin
      sensitivity assay, whether it serves as a biomarker of individual sensitivity and
      risk for head and neck cancer under our environmental conditions. The test is
      based on the measurement of the means of chromatid breaks induced by bleomycin in
      vitro in a single lymphocyte (break/cell=b/c). 156 head and neck cancer patients
      were matched not only with 295 healthy controls (146 non-smokers and 149
      smokers), but also with 51 strong alcoholic and smoking patients with liver
      disease whose lifestyle did not differ from that of the cancer patients. The
      aberrant cell frequency of cancer patients (2.85%), alcoholics (2.82%) and
      healthy smokers (2.81%) was similar and higher (p<0.03) than the values of non
      smoker controls (2.25%). Thus, the results of conventional chromosome analysis
      indicate the effect of exposure to mutagens, derived mainly from smoking. Mutagen
      sensitivity measured by the bleomycin assay was significantly higher in both the
      cancer- (1.13 b/c) and the alcoholic patients (1.29 b/c) compared with smoker
      (1.04 b/c) and non-smoker controls (0.98 b/c). The bleomycin sensitivity assay,
      therefore, seems to be the biomarker not only for the cancer, but also for a
      disease of the same aetiology such as alcohol-related liver disease. However, the
      method is not suitable for the assessment of individual cancer risk due to
      overlapping of b/c values with those of controls. The proportion of mutagen
      sensitive persons in the group of Hungarian controls is 42-49%, which is two-fold
      of those in the US and Western Europe. When we estimate the cancer risk, the
      results of bleomycin sensitivity assay are equivocal under our experimental
      conditions, and they must be applied cautiously even in combination with the
      results of chromosome analysis.

PMID- 12050712
TI  - [PET scanning in head and neck cancer]
AB  - INTRODUCTION: FDG (fluorine-labeled deoxy-glucose) and 11C-methionine positron
      emission tomography was evaluated in the diagnostics of head and neck cancer. PET
      scans were applied for identifying/staging relapse after oncotherapy or searching
      unknown primary tumor with metastatic lymph nodes of the neck. METHODS:
      Retrospective analysis of 22 patients examined by 17 (18)FDG and 15 (11)C
      methionine PET scan. In 9 cases indication was unknown primary tumor with
      positive neck, in 13 cases previously treated head and neck cancer patients were
      examined for recurrence/restaging. RESULTS: In searching for unknown primary
      tumor not detectable with conventional methods, PET was effective in 22%,
      however, false positivity and uncertain results were found as well. In restaging
      PET proved to be very effective (85%) to discover recurrences and to
      differentiate them from post-treatment (mainly irradiation) effects. In two cases
      silent distant metastase were detected. CONCLUSION: PET can provide valuable
      information about unknown primary tumors, recurrences after oncotherapy and
      distant metastases as well. Simultaneous use of FDG/methionine scans does not
      improve the results.

PMID- 12050711
TI  - [Genetic marker analysis in head and neck cancer]
AB  - Prognostication of head and neck cancer (HNCC) involves molecular identification
      of residual tumor cells, prediction of recurrence, distant metastases or
      secondary tumors and prediction of the sensitvity to therapy. Biomarkers of HNCC
      are mutations of p53, p16 and amplification of Cyclin D and E2F4. One hundred and
      fifty-two HNCC cases have been evaluated for p53, hMLH1, Cyclin D and p16 gene
      alterations using PCR-SSCP and Western blot analysis. P53 mutations of HNCC have
      been found in 37.5% of cases. However, 11% of the cases showed p53 mutations in
      the normal peritumoral mucosa suggesting "field cancerization" process. Mismatch
      repair gene mutations (MMR: hMHL1 and hMSH2) occurred with 17 and 8.6% frequency,
      respectively, while E2F4 mutations were even more frequent (21.4%) in HNCC. Our
      data suggest that E2F4 overexpression can be caused by the inactivation of the
      p16 gene in HNCC, while its mutations are most probably associated to the
      mutations of the MMR genes. These molecular informations can help to predict the
      biological potential of HNCC as well as the probability of the development of
      secondary HNCCs.

PMID- 12050714
TI  - [Radial forearm and fibula free flap reconstruction after radical resection of
      head and neck malignancies]
AB  - The incidence of head and neck cancer has been rapidly increasing in Hungary
      during the last decade. Most of these tumors are discovered in advanced stage,
      consequently, surgical removal of the tumor results in large complex defects in
      the soft tisses and bone elements of the face and neck. For optimal anatomical
      and functional reconstruction we perform free flap transfer in increasing number
      of cases. Between December 1993 and March 2001 in the Head and Neck Surgery
      Department of the National Institute of Oncology the defects after resection of
      head and neck tumors were reconstructed with free flaps in 85 cases. Radial
      forearm flap in 64 cases, fibula osteoseptocutaneous flap in 14 cases were used.
      In 87% of the patients the postoperative period was uneventful, the surgical
      complications were not more numerous than following traditional reconstructions.
      The average duration of operations became shorter by 2.5 hours during the last
      two years than before. In most of the cases we achieved good functional and
      esthetic results. The quality of life of the patients was excellent in 14%,
      almost normal in 73% and bad with serious problems of social life in 13%. It is
      surprising that there was no significant difference between the survival of neck
      node positive and negative patients. In our practice the replacement of large
      defects in the head and neck region with free flaps is a reliable and useful
      method for reconstruction.

PMID- 12050713
TI  - [Buccal flap reconstruction of oropharyngeal defects]
AB  - AIM: Introduction of a safe and reliable method for reconstruction of soft tissue
      defects after excision of T1-T2 and borderline carcinomas of the posterior part
      of the oral cavity and mesopharynx. METHOD: Operation of two male patients
      suffering from tonsillolingual carcinoma, one with recurrent tumour after
      irradiation, the other with untreated primary and neck metastasis. After excision
      of the tumour with mandibular splitting method only a random buccal transposition
      flap was applied for reconstruction. The flap was adapted anatomically into the
      defect. It is a modification of previously described methods. RESULTS: Both
      patients healed primarily with undisturbed blood circulation of the flap. The
      functional rehabilitation period was short, the flap tolerated the postoperative
      irradiation, a moderate trismus remained after completion of the treatment, but
      it was not attributable to the flap. CONCLUSION: The use of the single buccal
      transposition flap for reconstruction of smaller defects of the posterior part of
      the oral cavity seems to be a simple, reliable and safe method even after
      irradiation. The key of the acceptable functional results is the correct
      adaptation of the flap

PMID- 12050715
TI  - [Importance of 3D conformal percutan and brachytherapy treatment planning based
      on CT and MRI examinations in treatment of oral cavity tumors]
AB  - AIM: The importance of 3D conformal percutan and brachytherapy treatment planning
      based on CT and MRI examinations in treatment of oral cavity tumors. Introducing
      of the planning procedure and the selection aspects. METHOD: We present the
      treatment planning based on CT and MRI slices of an oral cavity tumor. The
      percutan or interstitial boost follow the percutan irradiation of the involved
      regions and lymph nodes, regarding to the target volume and the critical organs.
      RESULT: Our ADAC 3D planning system gives us the possibility to add the first
      line and the boost treatment plans, to determine and compare the dose
      distribution within the planned target volume and the radiation load of the
      critical organs. CONCLUSION: The comparative 3D radiation planning system allows
      higher local dose escalation required for the effective radiation treatment of
      oral cavity tumors with maximal protection of the surrounding healthy tissues.

PMID- 12050716
TI  - [Conformal radiotherapy of maxilla tumors]
AB  - PURPOSE: To demonstrate a conventional and a new therapeutic method of 3D
      treatment planning in maxilla tumors, the process of 3D treatment planning and
      its significance and to compare these two methods. METHOD: We performed 2D and 3D
      treatment plans. The ADAC planning system was used in the 3D treatment planning.
      CT and MRI scans were taken on the target volume and on each scan we demarcated
      the target volume and the critical organs. The irregular fields were obtained by
      3D graphic reconstruction provided by the treatment planning programme. RESULTS:
      Compared to the conventional treatment planning more favourable dose distribution
      was obtained within the target volume and the radiation burden of the critical
      organs was kept under their tolerance doses. CONCLUSION: In conformal 3D
      treatment planning the shape and size of the irradiated volume are in good
      conformity with those of the target volume. In this way the radiation burden of
      the critical organs and adjacent intact tissues can be reduced.

PMID- 12050717
TI  - [Modern radiotherapy techniques in the treatment of tumour of the base of tongue]
AB  - AIM: To demonstrate the role, the execution and the importance of the computed
      tomography (CT) based three-dimensional brachytherapy and conformal percutan
      radiotherapy in the treatment of the advanced tumour of the base of tongue.
      METHODS: Between January 1993 and June 2000, 27 patients with stage III-IV
      squamous cell cancers of the base of tongue were treated after 60 Gy percutan
      irradiation with interstitial, high dose rate brachytherapy (23 patients) or
      conformal, multi-fields radiotherapy (4 patients) as a boost. The dose of the
      boost irradiation varied between 12 and 24 Gy. RESULTS: Boost irradiation was
      well tolerated by the patients. The local tumour control at the mean follow-up
      period (39 months) was 52%. Using this two treatment methods in case of percutan
      conformal irradiation 6%, in case of brachytherapy 1.5% of the mandible received
      the prescribed boost dose. The spinal cord received a maximum of 15%, and 8% of
      the boost dose, respectively, depending on the two treatment types. CONCLUSION:
      With the help of these two radiotherapeutic modalities locally higher cumulative
      dose and better tumour control can be achieved without the higher risk of
      radiation injury of the surrounding normal tissues and the two most critical
      organs (medulla, mandible).

PMID- 12050718
TI  - [Neoadjuvant chemotherapy in head and neck cancer]
AB  - BACKGROUND: Neoadjuvant chemotherapy has an increasing role in multimodality
      treatment of advanced head and neck cancer. In this paper we summarize our first
      results with this treatment. METHOD: Thirty-five, previously untreated, mostly
      inoperable head and neck cancer patients were given two cycles of Cisplatin and
      5FU chemotherapy. We continued the therapy only in case of regression until four
      cycles, then the patients received surgical and/or radiotherapy according to
      their status. After the treatment patients' status was regularly evaluated.
      RESULTS: We detected 4 complete and 20 partial responses after the chemotherapy.
      Three patients became eligible for a radical operation. At this moment 10
      patients are free of tumor, 8 patients died in consequence of the tumor, we have
      no data in 3 cases, 3 patients are given palliative therapy because of
      progression, 4 patients are receiving radiotherapy and 7 patients with partial
      response are candidates for further active oncotherapy. CONCLUSIONS: Although the
      number of the patients we treated is too small for a statistical analysis, our
      results are similar to the conclusion of the large randomized studies: after
      neoadjuvant chemotherapy of advanced head and neck cancer partial response can
      improve the result of surgical or radiological treatment. Neoadjuvant
      chemotherapy does not improve survival in advanced head and neck cancer, but it
      is of great importance because of better quality of life of patients, especially
      those who had organ preserving therapy.

PMID- 12050719
TI  - [Low-dose Taxol radiosensitization in locally advanced head and neck cancers]
AB  - INTRODUCTION: Combined modality treatment with chemotherapy and radiotherapy in
      locally advanced head and neck cancers is an effective and often the only
      treatment with a chance of cure. An alternative is to use chemotherapeutic agents
      at low doses as radiosensitizers. In this study we examined the radiosensitizing
      effect of low dose Taxol in locally advanced head and neck cancer. Patients and
      methods: 26 patients with locally advanced squamous cell carcinoma of the oral
      cavity and the oropharynx were treated with external beam radiotherapy up to
      doses of 66-70 Gy and received concomitantly 2 mg/m(2) Taxol intravenously three
      times a week. Response rates according to WHO criteria, side effects according to
      the National Cancer Institute Common Toxicity Criteria, overall and progression
      free survival were evaluated. RESULTS: All patients completed the therapy. Median
      radiation dose was 66 Gy, Taxol dose 40 mg/m(2) and treatment duration 54 days. 8
      weeks after completion of therapy complete response was 30.8%, partial response
      34.6%, stable disease 11.5% and progressive disease 23.1%. The median follow-up
      time was 25 months (9-36). At the cloes- out date 12 (46,1%) of the patients were
      alive, 9 without evidence of disease. The estimated median overall survival was
      22 months (CI 14.2-34.6), the median progression-free survival 12 months (CI 5.2
      18.8). We observed four grade 4, fourteen grade 3 and numerous grade 1-2 side
      effects. There was no treatment related death. DISCUSSION: Our regimen resulted
      in a worse response rate than the aggressive chemoradiation protocols treating
      the same disease. However, the two-year survival was comparable with the results
      of other studies. The advantages of our schedule are that it is well tolerated,
      easy to perform on an outpatient basis, resource effective and does not
      deteriorate the general condition of the patients, therefore successive therapy
      can be carried out immediately if necessary. We intend to evaluate the
      effectivity of this treatment in a study comparing radiotherapy with Taxol
      sensitization versus radiotherapy alone.

PMID- 12050720
TI  - [Combined modality treatment of locally advanced oral and oropharyngeal cancer
      following primary radiotherapy with and without taxol radiosenzitization]
AB  - AIM: To determine the effect of radiosensitization with Taxol and multimodality
      treatments on the survival of advanced oral and oropharyngeal cancer. Patients,
      methods: 56 patients with St. III-IV oral or oropharyngeal cancer were treated
      with external beam radiotherapy; 26 of them were sensitized by low-dose
      paxlitaxel and 30 were irradiated traditionally. The median follow up was 23
      months (17-36). Endpoints of the study were: response to radiotherapy,
      progression-free and overall survival and the results of surgery and chemotherapy
      following radiation. RESULTS: 73.3% (41/56) of treatments resulted in CR or PR
      with median 10 months (0-33) progression-free and 14 months (4-33) overall
      survival. There was no significant difference between the radiosensitized and
      traditional radiotherapy group (p=0.6). The survival was significantly influenced
      by the stage of tumor and the response to primary radiotherapy. Seven (38.9%) of
      16 patients treated also by either surgery or chemotherapy for recurrent or
      residual disease are free of cancer, 6 (35%) alive with tumor and 5 (26.1%) died
      with median survivals of 21, 20.5 and 18 months, respectively. Those treated only
      with radiotherapy with or without sensitization are free of cancer in 31.6%,
      alive with cancer 5.3%, died 63.2%. CONCLUSION: There were significant
      correlation between tumor stage, response to radiotherapy and combined modality
      treatment, and surival. The radiosensitizing effect of Taxol was not obvious so
      far, it may be apparent in the future by analyzing the long term survival data.

PMID- 12050721
TI  - [Colorectal cancer screening: a new strategy for the demonstration of occult
      intestinal bleeding]
AB  - The topic of colorectal cancer screening is discussed with special emphasis on
      its history and improvement of its methodology. The author's own results are
      evaluated in terms of international data published in literature in order to put
      forward his proposals for a new strategy. The devastating power and endemic
      character of colorectal cancers is stressed and the development of screening
      activities is recommended to accomplish within the frame of the complex health
      service.

PMID- 12050722
TI  - [Autologous hematopoietic stem cell transplantation in chronic myeloid leukaemia
      with different clinical stages]
AB  - For most chronic myeloid leukaemia patients the option of a potentially curative
      allogeneic stem cell transplantation is not available because of age or lack of
      donor. Alternative therapy with interferon-alpha appears to prolong survival but
      is probably not curative. The aim of the study is to analyse the clinical results
      of the first Hungarian autologous transplantations in CML. METHODS: Seven
      patients were treated with ICE-based regimen plus G-CSF with the aim of
      mobilising and collecting Ph-negative peripheral stem cells in the setting of
      autologous transplant program. Five patients had CML in first chronic phase and
      two in accelerated phase. All patients have been previously treated with
      interferon-alpha. RESULTS: Median value and ranges for harvested mononuclear
      cells, CD34(+) cells and CFU-GM were: 5.65x10(8)/kg (2.61-11.38), 1.48x10(6)/kg
      (0.216-3.5) and 3.43x10(4)/kg (0.243-11.6), respectively. Four out of seven
      autologous grafts have been transplanted. Busulfan conditioning was used in one
      case and TBI/Cy conditioning in three patients. All patients are alive and well
      post-transplant being on interferon-alpha therapy. CONCLUSIONS: Based on the
      clinical advantages of autologous transplantation including long-term chronic
      phase, achievement of second chronic phase and improved response to interferon
      alpha therapy, the procedure can offer an alternative treatment in CML in lack of
      HLA-identical donor.

PMID- 12050723
TI  - [Clinical and immunopathological significance of chimerism in bone marrow and
      organ transplantations]
AB  - Chimerism is an exceptional immunogenetic state, characterized by the survival
      and collaboration of cell populations originated from two different individuals.
      The prerequisites to induce chimerism are immunosuppression, myeloablation or
      severe immunodeficiency of the recipients on one side and donor originated immuno
      hematopoietic cells in the graft on the other. Special immunogenetic conditions
      to establish chimerism are combined with bone marrow transplantation, transfusion
      and various kinds of solid organ grafting. There are various methods to detect
      the type of chimera state depending on the immunogenetic differences between the
      donor and recipient. The chimera state seems to be one of the leading factors to
      influence the course of the post-transplant period, the frequency and severity of
      graft-versus-host disease (GVHD), and the rate of relapse. However, the most
      important contribution of the chimeric state is the development of graft versus
      leukemia (GVL) effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic
      BMT in CML patients and its consequence on chimera state and GVL effect is
      demonstrated.

PMID- 12050724
TI  - [Therapy of multiple myeloma]
AB  - Multiple myeloma (MM) is a haematological malignancy characterised by the clonal
      expansion of malignant plasma cells within the bone marrow. It accounts for 10%
      of all haematological malignant diseases and 1% of all malignancies. The median
      age of patients at the time of the diagnosis is 70 years. The characteristic
      clinical features of MM are bone marrow failure, susceptibility to infections,
      bone pain, pathological bone fractures, hypercalcaemia, and renal failure. Though
      MM is currently incurable, the important progress in chemotherapy has resulted in
      an improvement in survival from a median of 7 months in the 1950-ies to about 3
      years today. Advances in the diagnosis and in supportive treatment of infections,
      hypercalcaemia, and renal failure also contributed to the prolongation of
      survival. For decades, the gold standard of treatment had been oral melphalan
      alone or in combination with prednisolone. Combination chemotherapy has not
      improved overall survival (OS), but these regimens have led to the prolongation
      of event-free survival (EFS) and also to a better quality of life. High-dose
      chemotherapy with haemopoietic stem cell rescue resulted in a great improvement
      in EFS as well as OS. For those very few who have an HLA-compatible donor and are
      under 55, allogeneic bone marrow transplantation offers the best hope of survival
      but comes at a greatly increased risk of toxicity. There are conflicting data in
      the literature concerning the role of interferon-alpha; it seems to be able to
      prolong the duration of the plateau phase. Current treatment is moving towards an
      approach using sequential therapy. This involves induction therapy proceeding to
      high-dose chemotherapy with some form of stem-cell rescue. Bisphosphonates reduce
      hypercalcaemia, bone pain and can inhibit bone destruction. They also possess a
      direct antitumor activity. The better understanding of the pathomechanism of the
      disease gives the opportunity of the application of new therapeutic modalities
      such as antagonising the effect of interleukin-6 (IL-6), or idiotypic
      vaccination.

PMID- 12050725
TI  - [The World Health Organization classification of lymphoid neoplasms]
AB  - The European Society of Pathology and the Society for Hematopathology have
      developed a new World Health Organization (WHO) classification of hematological
      malignancies. The classification is based on the principle that the
      classification is a list of entities defined by the combination of morphology,
      immunophenotype, genetic and clinical features. The WHO classification is a new
      basis of communications between pathologist and oncologist which will help to
      understand and treat hematological malignancies

PMID- 12050726
TI  - [Recommendation: high risk (aggressive) non-Hodgkin lymphoma (NHL)]

PMID- 12050727
TI  - [Clinical features and guidelines of treatment of mucosa-associated lymphoid
      tissue lymphoma of stomach]
AB  - The mucosa-associated lymphoid tissue (MALT) lymphoma is a very indolent disease.
      Its most common site is the stomach. The lymphoma begins as a reactive lymphocyte
      accumulation mostly due to an infection of Helicobacter pylori (HP). Through
      repeated mutations this tissue is transformed into the characteristic MALT
      lymphoma. At the time of the diagnosis the lymphoma is usually localised, but in
      one third of the patients the disease has already been disseminated. There are
      not any commonly accepted guidelines of therapy concerning this primary gastric
      MALT lymphoma, but certain general tendencies have already been defined. In the
      early disease the aim of the treatment is curative with the preservation of the
      stomach as much as possible. In a considerable number of cases, when the surface
      of the stomach is affected by HP, one can achieve histological and molecular
      biologic remission after eliminating the bacteria. However, there is no such
      therapeutic consequence to be expected in case of a deeply invasive tumour. The
      optimal treatment of patients of this group as well as those whose disease is
      resistant to HP eradication treatment together with those who are HP negative is
      radiotherapy or surgery with chemotherapy. In this latter case quality of life
      becomes worse. In an advanced case cure is impossible and chemotherapy is the
      most effective to ease the patient's state.

PMID- 12050729
TI  - [Recommendation: Hodgkin disease]

PMID- 12050728
TI  - [Progress in the treatment of non-Hodgkin's lymphomas]
AB  - The authors analyze the progress achieved in the treatment of low-grade as well
      as of high-grade non-Hodgkin's lymphomas. The challenging task in the treatment
      of low-grade or indolent lymphomas still is to decide whether watchful waiting is
      sufficient or whether chemotherapy is necessary and how aggressive this treatment
      should be. Among the new chemotherapeutic agents the role of purine analogues
      should be emphasized, fludarabin is especially important in the treatment of
      chronic lymphocytic leukemia and follicular lymphoma, while pentostatin and
      cladribine have revolutionized the treatment of hairy cell leukemia. Treatment
      with monoclonal antibodies, radioimmunoconjugates as well as autologous or
      allogeneic stem cell transplantation are potential new therapeutic options in the
      treatment of low-grade non-Hodgkin's lymphomas. In the case of aggressive non
      Hodgkin's lymphomas risk-adapted strategies help the choice between standard or
      more intensive treatment options. In patients with relapsed high-grade lymphomas
      stem cell transplantation is indicated. In patients with marginal zone lymphoma
      the combination of hyperCVAD protocol + stem cell transplantation greatly
      improves prognosis.

PMID- 12050730
TI  - [Impact of DNA chips on haematological oncology]
AB  - As the Human Genome Project hurtles towards completion, DNA microarray technology
      offers the potential to open wide new windows into the study of genome
      complexity. DNA chips can be used for many different purposes, most prominently
      to measure levels of gene expression (messenger RNA abundance) for tens of
      thousands of genes simultaneously. But how much of this data is useful and is
      some superfluous? Can array data be used to identify a handful of critical genes
      that will lead to a more detailed taxonomy of haematological malignancies and can
      this or similar array data be used to predict clinical outcome? It is still too
      early to predict what the ultimate impact of DNA chips will be on our
      understanding of cancer biology. There are many critically important questions
      about this new field that are yet unaddressed. By the publication of this
      article, it is hoped that the technology of DNA chips will be opened up and
      demystified, and that additional opportunities for creative exploration will be
      catalysed.

PMID- 12050731
TI  - [The role of syndecans in lymphoid systems]
AB  - Syndecans, transmembrane heparan sulfate proteoglycans, play an important role in
      cell-cell and cell-matrix interactions, as receptors/co-receptors of matrix
      elements, cytokines, growth factors. These functions are partly non-specific and
      due to the heparan sulfate chains attached to the ectodomain, and partly specific
      related to the transmembrane and cytoplasmic domains of the core protein. In
      hemopoietic cells syndecan-1 is expressed in certain B cells, in pre-B cells and
      plasma cells. In lymphoproliferative diseases this normal syndecan-1 expression
      of plasma cells is retained in myelomas/plasmocytomas, other lymphoplasmocytic
      NHL subtypes and primary effusional lymphomas. Syndecan-1 expression is probably
      gained in B-CLL, and lost in other NHLs of pre- or post-follicular origin. These
      results suggest that the expression of syndecan is essential for some NHLs,
      probably ensuring the required connections to the microenvironment. From a
      diagnostic point of view, syndecan-1 is a very useful phenotypic marker to
      identify cells with plasmocytic differentiation. The importance of syndecan
      expression in CLL and Hodgkin-lymphoma still requires further studies.

PMID- 12050732
TI  - [Expression of metastasis associated proteins, CD44v6 and NM23-H1, in pediatric
      acute lymphoblastic leukemia]
AB  - Two metastasis associated proteins, CD44v6 and NM23-H1, are expressed by normal
      lymphoid cells, the former serving as activation marker and the later as a
      constitutive protein. CD44v6 is considered as a marker of poor prognosis of
      various hematological cancers but its expression was not demonstrated in
      childhood acute lymphoblastic leukemia (ALL). On the other hand, NM23-H1 is
      considered as a differentiation inhibitory factor in various hematological
      cancers and as a marker of poor prognosis. Therefore we have analyzed the
      expression of CD44v6 and NM23-H1 in bone marrow of sixteen pediatric ALL patients
      using immunocytochemistry. For the first time, we have demonstrated the
      expression of CD44v6 protein epitopes on leukemic cells in a proportion of ALL
      cases (6/16), primarily in the medium/high risk group (except one case),
      suggesting a possible association to an unfavorable outcome. On the other hand,
      NM23-H1 protein expression was maintained in leukemic cells in 50% of both low
      and medium/high risk ALL cases. The majority of the pediatric ALL cases expressed
      only one of the metastasis associated proteins (10/16). This feature is highly
      similar to the observations made in several adult solid cancers. The potential of
      CD44v6 expression in leukemic cells as prognosticator in pediatric ALL has to be
      evaluated in a larger clinical trial.

PMID- 12050734
TI  - 23(rd) San Antonio Breast Cancer Symposium.

PMID- 12050733
TI  - [Management of cancer pain]
AB  - The morphin-analogue, Durogesic, has robust analgetic effect without repeated
      side-effects and is suitable for special applications providing it as the first
      choice for therapy of cancer pain and as an acceptable alternative for CR
      morphin. Clinical studies not only provided evidences for the pharmacological
      effectivity of Durogesic but suggested that the quality of life of cancer
      patients improved significantly as well.

PMID- 12050735
TI  - [Hungarian experience in the treatment of childhood acute lymphoblastic leukemia]
AB  - The Hungarian Pediatric Oncology Study Group treated 362 acute lymphoblastic
      leukemia patients between 1990 and 1995 using the the ALL-BFM 90 protocol. The
      modified protocol, ALL-BFM 95, was used later to treat 257 patients. The two
      protocols were similarly successful to treat low and medium risk cases. However,
      the ALL-BFM 95 protocoll was more efficient to treat high risk patients and
      resulted in 10% increase in survival. The Western-European results are superior
      by 10-15% compared to the Hungarian data mainly due to the relatively high
      proportion of the early death in Hungary. Improvement of these data can only be
      expected from the development of the diagnostic potentials and from further
      improvement of treatment of the high isk patients.

PMID- 12050736
TI  - [Survival of Ewing' s sarcoma patients in Hungary]
AB  - Correlation between different prognostic factors and the overall survival of
      Ewing's sarcoma patients has been investigted. In this study data have been
      selected from the databank of Hungarian Pediatric Oncologist Section (1988-1999)
      (n=65). Whenever it was possible statistical analysis has been performed.
      Results: In our patients time interval from the primary symptoms to the diagnosis
      was 2-16 months. The average event-free survival in patients suffering from
      Ewing's sarcoma without metastasis is 0.39. Meanwhile, this value in patients
      with pulmonary or other metatasis is 0.24 (Kaplan-Meier analysis). Conclusion:
      Our results show a moderate difference between the Hungarian and the
      international event-free survival. Late detection is one of the answers of this
      discrepancy.

PMID- 12050737
TI  - [The role of radiotherapy in the prevention of recurrence and central nervous
      system metastases in childhood medulloblastoma]
AB  - PURPOSE: To present the postoperative radiotherapy technique in children with
      medulloblastoma, and analyse the effectiveness of radiotherapy and the survival
      data. MATERIALS AND METHODS: 66 consecutive children (45 male and 21 female)
      received postoperative chemotherapy and radiotherapy between 1986 and 1998. The
      mean age was 8.3 years. The radiotherapy was performed with linear accelerator
      9MV X-ray irradiation. The high risk patients received 36 Gy craniospinal
      irradiation, the low risk patients recived 30 Gy. The boost irradiation to the
      posterior fossa was 20 Gy in both patient groups. The patients received multi
      drug chemotherapy immediately after the tumor resection. The radiotherapy started
      6-8 weeks after the operation. RESULTS: All 66 patients were evaluated. The mean
      follow-up time was 45.4 months. The chance of cure is higher at age 8 or more,
      and less favorable under age 8. After 60 months 68.6% of children under age 8 and
      75.9% older than 8 are alive. 20 children (64.5%) are alive after radical
      tumorectomy and 11 died. The 5 year overall survival was 71%. Recurrence was
      observed in 23/66 cases, it was the most frequent cause of death. Local failure
      was in posterior fossa in 15 patients (68.2%). CONCLUSION: The radicality of
      operation had no significant influence to the overall survival. The tumor stage,
      age of patients, risk group and metastases are important prognostic factors.

PMID- 12050738
TI  - [Childhood liver tumor in Hungary: two interesting clinical cases]
AB  - Hepatic tumors account for 0.5-2% of all childhood tumors in Hungary, based of
      the data last ten years. More than half of the cases were histologically
      malignant. The worldwide incidence of malignant hepatic tumors is 1.6 / 1
      million. Here we present two patients with hepatoblastoma. In the first case the
      size of the initially inoperable tumor diminished following the chemotherapy and
      total surgical resection became possible. No sign of relapse occurred so far. The
      second case included a congenital hepatic tumor which was remarkable because of
      its unusual clinical presentation and histology.

PMID- 12050739
TI  - [Early diagnosis of testicular cancer]
AB  - PURPOSE: The authors analyze their 3-year results of the "educational and early
      detection program for testicular cancer". The goals of the program are to reduce
      the duration of symptoms and to improve early detection. METHODS: Advertisements
      were placed in the media describing the early signs of testicular cancer, the
      risks factors, the correct method of self-investigation and the importance of
      early detection. Between 1 April, 1995 and 1 April, 1998 5056 volunteers were
      examined. They underwent physical and ultrasound examination of the testicles,
      and in case of suspicious findings, tumor markers (alpha-fetoprotein, human
      choriogonadotropin) were checked. RESULTS: Testicular tumors were found in 1.28%
      of patients with symptoms (testicular enlargement or nodules). No tumor was found
      in the population that was symptom-free, or in patients with pain, sensitivity to
      palpation, or unrelated complaints. Of the patients with a palpable lump and
      swollen testicles, 4.5 and 3.9% were found to have tumors respectively. In total
      32 testicular tumors were detected in 30 patients: 15 (2 bilateral) seminomas, 13
      non-seminomas and 4 benign tumors. The occurrence of malignant testicular tumors
      was most frequent, 1.6% in the age group between 15 and 40 years. The stages were
      as follows: 9 I/A, 9 I/B, 1 I/S, 3 II/A, 1 II/B and 2 III/B. One patient was lost
      to follow-up after castration. All the other patients achieved complete
      remission. CONCLUSION: Despite the increasing incidence of testicular cancer
      screening of asymptomatic men does not lead to detection of tumors. The awareness
      of the early signs associated with cancer, self-examination, ultrasound
      examination of the testicle help in establishing an early diagnosis, nevertheless
      a widescale program for the early detection of testicular cancer is not
      justifiable. Effective early detection should be based on an educational program
      for the population at risk, the appropriate training of doctors and staff engaged
      in the health care of the young, and the initiation and facilitation of early
      ultrasound examination at the first symptoms. Serum markers play a limited role
      in early diagnosis.

PMID- 12050740
TI  - [A case of central nervous system atypical teratoid / rhabdoid tumor]
AB  - The atypical teratoid / rhabdoid tumour is a rare type of tumours of central
      nervous system appearing usually under 2 years of age, bearing a rather bad
      prognosis and it may cause serious differential diagnostic problem. The tumour is
      characterized histologically by the presence of the rhabdoid cells,
      immunohistochemically by vimentin, SMA, EMA positivity, the frequent presence of
      cytokeratin, GFAP positivity, but germ cell markers: AFP, hCG negativity,
      cytogenetically by aberrations of chromosome 22. The case of a one and half month
      old female infant is presented, who died 8 months after the appearance of the
      first symptoms. The diagnostic possibilities and the unsolved problem of the
      therapy are discussed.

PMID- 12050741
TI  - [Frequent infections of neutropenic pediatric patients and therapeutic
      modalities]
AB  - Neutropenia, resulting from intensive chemotherapy is a common problem. The
      appearance of fever in neutropenic patients should always raise the suspicion of
      infection and should be followed by an intensive diagnostic evaluation and start
      of antibacterial treatment. The authors analyzed the association between isolated
      bacteria from blood cultures and the clinical background of all febrile episodes
      that occurred in neutropenic children in a two-year long period. Comparable to
      the international trends, our results suggest an increased prevalence of the Gram
      positive organisms causing bacteriaemia. The clear majority of the isolated
      bacteria was coagulase-negativ Staphylococcus (cnS), which is a multiresistant
      strain, and sensitive only to the glycopeptide antibiotics. This latter fact can
      be a consequence of the frequent use of central venous catheters. The empirical
      therapy, the therapy used in microbiologically and clinically proved infections,
      and the supplementary and prophylactic methods of treatment are presented.

PMID- 12050742
TI  - [Nested PCR detection of WT1 expression in the peripheral blood in childhood
      acute leukemia]
AB  - Detection of minimal residual disease (MRD) in childhood leukemia is not possible
      by cytomorphology or Southern blotting due to their low sensitivity. On the other
      hand, the use of DNA markers and PCR amplification is helpful in a smaller
      proportion of leukemia cases (20-30%). Since childhood leukemia is characterized
      by WT1 gene expression in the majority of cases,monitoring of WT1 expression in
      the peripheral blood was suggested to be a method of choice to detect MRD. We
      have studied 22 newly diagnosed childhood acute leukemias and 17 cases in
      remission. As controls, 19 patients with non-leukemic diseases were included. The
      majority of our acute leukemia cases (80%) were proved to be WT1 expressors using
      a highly sensitive nested PCR technique. Ten WT1 + cases have been monitored for
      a year throughout the inicial therapy phase, using peripheral blood tests. We
      observed that in 20% of the follow-up cases MRD was suggested which was not
      detectable by any other methods. It is our intention to introduce this new
      molecular technique into the clinical management of childhood acute leukemia.

PMID- 12050743
TI  - [Making Decisions on the Resources for Cancer Control]
AB  - We aim at modelling the strategic decision making process in case of devoting
      resources to a governmental cancer control program. We use a model based on the
      theory of Analytic Hierarchy Process. In this article we describe the
      characteristic features of such a decision making process and reveal the
      complexity of the problem underlying the decisions. A second article will present
      and discuss the results from the application of the AHP model. Interventions
      which are capable of decreasing the burden of cancer in a society need strategic
      approach. Decisions on interventions seem inevitable to be based on and balance
      between the priorities and the available resources. There is not much doubt about
      it that the reason for setting the priorities arises on the one hand from the
      scarcity of resources. On the other hand, priorities evolve on other bases, and
      are supposed to "guide" health policy makers devoting the scarce resources. In
      general, a strategic mode of thought has been based on assumptions, which, in
      case of cancer control enhance the necessity to assess information on cancer and
      cancer patients, and to understand the factors contributing towards better
      health. The capabilities of the NCCP achieving its aims by preventing the
      development of cancer diseases (primary prevention), by making use of the means
      of early detection and appropriate therapy (secondary prevention), and by
      providing modern (comprehensive) tertiary prevention are inevitably affected by
      the priorities. Health policy should assume a responsibility for enforcing
      certain priorities and should be aware of the long-term interest of the
      population. To solve the problem we restrict the model to a simple three level
      one, representing the goals, the criteria, and the alternatives of the resource
      allocation. We determine "decreasing the burden of cancer" as the overall goal.
      "Distributive justice" "cost-effectiveness", "human rights", "evidences", and
      "standpoints of a community" serve as criteria, while "primary prevention",
      "early detection and therapy, both belonging to the secondary prevention",
      "tertiary prevention", "research", and "education" form the alternatives.

PMID- 12050744
TI  - [Prevention: a real possibility to repress lung cancer]
AB  - In the lack of effective treatment, the role of prevention has increased in the
      repressing of lung cancer. Smoking being a pathogenetic factor in the development
      of lung cancer is an accepted fact. Because of this, primer prevention means
      first of all the reduction of smoking both with the help of preventing smoking
      and cessation. A bigger - historical - debate has developed around secunder
      prevention: the effective screening of lung cancer. Although it was observed that
      staging rate and resecability had been more advantageous in the screened group,
      the screening of lung cancer was declared ineffective, because mortality did not
      improve. The change of approach can be felt from the middle of the 90's. Nowadays
      the creation of a multimodal lung cancer preventional strategy is in the center
      of researches. The screening of risk groups can mean the solution with the aid of
      biomarkers, chest X-ray and spiral CT. In Hungary, with the infrastructure of
      existing lung-screening network the up-to-date screening of risk groups seems to
      have reality in the near future.

PMID- 12050745
TI  - [Diagnosis of lung cancer]
AB  - Lung cancer is the most common malignant tumor among male and second among
      female. The most effective diagnostic tool would be the early detection of the
      lung cancer. The diagnosis of tumors has to be based on patho-morphological
      findings. The invasive diagnostic tools can be used if the proved lung process
      has any therapeutic consequence. Only an experienced team has the chance to
      examine quickly and effectively the patients.In Hungary there are pulmonological
      centers where these teams consisting of pneumonologist, radiologists and
      pathologists are working effectively.

PMID- 12050746
TI  - [Tumor markers and prognostic factors of the primary lung cancer]
AB  - Primary bronchial cancer is the most common cause of cancer death worldwide, and
      it shows a steadily increasing incidence. Beside classical histological typing
      and grading, immunohistochemical, cytometric, and molecular biological parameters
      are highly needed to assist light microscopy investigations to better
      characterize primary bronchial cancers. In this work the author summarizes the
      main tumor markers and prognostic factors in lung cancer studied intensively at
      present. Serum markers as well as different tissue markers, such as cell
      proliferation markers, oncogenes, growth factors, apoptosis markers and
      vascularisation markers, tumor suppressor genes and markers of drug resistance
      are discussed in details. The methods currently used in this field are also
      mentioned and the data of the literature is often completed with results of the
      author's own investigations. An overview is given about the role of tumor markers
      in the early detection of lung cancer, in the assessment of tumor aggressiveness,
      and in therapy of lung cancer. The aim of this work is to create a bridge between
      the research laboratory in which lung cancer is studied sometimes using very
      sophisticated techniques and the bedside with all its practical, difficult but
      very important questions. Getting closer the theory and the practice can be very
      promising in the establishment of a fruitful collaboration in order to be more
      effective in the fight against lung cancer.

PMID- 12050747
TI  - [Changes in algorythm of surgical management for non-small cell lung cancer
      (NSCLC)]
AB  - In Hungary the incidence of lung cancer is growing further and the proportion of
      patients undergoing surgery is less than 30%. Some improvement is indicated by
      the rate of explorations decreasing to less than 10%. On the other hand the
      number of adenocarcinomas has grown to take over the position of the squamous
      cell carcinomas among the patients operated on. In the recent few decades only
      some minor changes have occurred in the surgical treatment. For this reason when
      operability has been established new perspectives have been reviewed before
      drawing conclusions on the number of cases qualifying for resection. Phrenic and
      recurrent nerve lesions and in some cases metastases in some other organs do not
      mean inoperability in the absolute sense any more. Based on the new TNM system
      the criteria of the qualification for and the date of resection are identified by
      staging implemented reliably and in details. Palliative surgery may also be
      possible in some selected cases. A complex approach to the treatment of lung
      cancer is clearly coming into the focus of our attention. Though a resection is
      the most important episode here an adjuvant (post-operative) therapy and most
      recently added that a neoadjuvant (pre-operative) therapy shall improve the
      patient's chances for survival further, enhancing the favorable result caused by
      the resection itself. Both the limits and the options of he surgical treatment
      administered in the cases of metastases in the lung, the brain and the solitary
      suprarenal gland are discussed in details in the cases of NSCLC.

PMID- 12050748
TI  - [Radiotherapy in lung cancer. Mandatory or optional?]
AB  - The purpose of the paper is to outline the current treatment strategies in lung
      cancer focusing on the possibile role of radiotherapy. METHOD: It defines the
      place of radiotherapy at the main histological types and stadiums proposing
      indications according to evidence based medicine. CONCLUSIONS: Radiotherapy is
      mandatory in non-operated NSCLC st. I-II in perioperative or palliative
      management of superior sulcus tumours; in the combined modality treatment of
      limited SCLC and in postoperative adjustment of resected single brain metastasis
      of lung cancer. It is optional after NSCLC segmentectomy; in palliation or
      postoperative adjuvation of NSCLC st. III Radiotherapy can be chosen as a part of
      best supportive care at NSCLC st. IV extensive SCLC and in case of multiple brain
      or localised lytic bone metastases.

PMID- 12050749
TI  - [The big dilemma: the chemotherapy of non-small cell lung carcinoma]
AB  - The most problematic area in pulmonary oncology is the chemotherapy of non-small
      cell lung carcinoma and its place in the therapeutic strategy. Chemotherapy based
      on the earlier alkylating agents worsened survival of NSCLC patients. That was
      the reason for the nihilistic approach by many colleagues toward chemotherapy in
      NSCLC. Today this question has been resolved. Platinum based combined
      chemotherapy significantly prolongs survival and improves quality of life. Other
      possibilities are to incorporate the new chemotherapeutic agents (taxanes,
      Gemcitabine, Vinorelbine, Irinotecan) into the chemotherapeutic regimens. These
      agents improve the response rate and the quality of life and can be safely
      administered in outpatient bases, although in comparison to the earlier agents
      the survival gain is moderate. In early stages the role of adjuvant chemotherapy
      is questionable. Chemotherapy, surgery and postoperative irradiation may all have
      a role in the case of N2 disease.In locally advanced disease the use of
      radiochemotherapy is recommended. In advanced NSCLC chemotherapy is suggested in
      good performance status. The author summarises the role of chemotherapy in NSCLC,
      based on literature and on his own experience.

PMID- 12050750
TI  - [Chemotherapy of small cell lung cancer]
AB  - The author summarizes the most recent information on small cell lung cancer.
      Reviews the epidemiology, prognostic markers and stages of small cell lung cancer
      Details the more frequently used combined therapeutic modalities, the criteria of
      the optimal therapeutic approaches and the achieved remission rates. Based on the
      most recent data, summarizes the new chemotherapeutic agents and their most
      effective combinations, the second line treatment and immunotherapy. Finally
      tries to answer the most frequently asked questions.

PMID- 12050751
TI  - [Supportive therapy of lung cancer patients]
AB  - The effectiveness of cancer treatment given to lung cancer patients is indicated
      by the asymptomatic and non-toxic survival time. The goal is not to prolong the
      patients' suffering, but to lengthen the duration of the best quality of life
      lived (Time Without Symptoms and Toxicity-TWIST). Supportive care is the
      prevention and management of side effects which occur during therapy
      (chemotherapy, radiotherapy, surgery) given to patients suffering from cancer.
      Supportive care is the widespread activity of doctors, nurses and social workers,
      including psychosocial assistance and rehabilitation through the various stages
      of illness till death. Though palliative therapy is understood to be the high
      level and professional treatment of terminally ill patients in those cases where
      curative measures are not possible anymore, supportive and palliative treatment
      often overlap (e.g. pain control, cachexia, obstructive syndromes). Palliative
      care is part of supportive therapy. The goal of supportive care is to reduce the
      patients' subjective symptoms to the minimum ("well being") during therapy,
      follow up and consequently until death. The essence of supportive care is to keep
      the patients' quality of life on the highest possible level. This article
      summarizes the pathophysiology, prevention and therapy of the most frequently
      occuring side effects observed during the management of lung cancer patients.

PMID- 12050752
TI  - [The role of repeated transurethral resection in the treatment of bladder tumor]
AB  - Complete removal of the tumour or deep invasion can be proven by repeated
      transurethral resection of bladder wall at the previous tumour site. Six weeks
      after transurethral resection of bladder tumour (TURB), in all but TaG1 cases
      repeated resection were performed for the evaluation of radicality in 62
      patients, 43 males and 19 females, suffering bladder cancer, from October 1998.
      In the case of positive histology another resection was performed for security
      reason. In the case of 38 superficial (Tis, Ta, T1) cancers, repeated resection
      revealed negative, identical or different T stage compared with previous
      histology in 28, 5 and 5 cases, respectively. In 7 cases repeated resection was
      applied as second intervention after the incomplete resection of large tumour
      mass. Indication of repeated resection was insufficient depth of resection and
      carcinoma in situ in 13 and 4 cases, respectively. Based on our data, we conclude
      that repeated resection should be performed when tumour-free status is not
      justified and biopsy according to Bressel was not taken.

PMID- 12050753
TI  - [Characterization of laryngopharyngeal tumors. Tumor size and vascularization]
AB  - A recent survey of head and neck cancer indicated a sharp difference in survival
      between cancer of the hypopharyx and cancers formed in other head and neck sites.
      We have analyzed tumor size relative to clinical stage and vascularization as
      possible causes for such a difference in a series of 21 patients with cancers of
      the laryngopharynx (11 glottic and 10 hypopharyngeal). We found that the volume
      of the smallest cancers of the larynx at stage 2 are significantly larger than
      the volume of the cancers of the hypopharynx at stage 4 (p<0.05). Next, we have
      determined by immunohistochemistry and morphometry the microvessel density (MVD),
      microvessel perimeter (MVP) and VEGF expression of laryngo-hypopharyngeal
      cancers. Analysis of these data indicates that there is no difference in
      vascularization and VEGF expression between these two tumor types. These data
      strongly suggest that the invasive-but not the angiogenic phenotype of
      hypopharyngeal cancer cells could be responsible for the more aggressive
      biological behavior of this head and neck cancer subtype.

PMID- 12050754
TI  - [Tumoral sinuses or vascular channels in tumors. Legacy of B. Kellner]
AB  - The re-discovery of the tumor cell-lined vascular channels and the possible
      pathomechanism (vasculogenic mimicry) earned major attention in the literature.
      This phenomenon is known for 60 years following B.Kellner, later supported by
      several groups, however its significance is still not known. The two new form of
      tumor blood supply, the incorporation/apoptotic remodeling of the preexisting
      vasculature and the latest discovery of endothelial gene expression in tumor
      cells suggest two alternative mechanisms for the development of tumor sinuses or
      vascular channels. The existence of these sinuses in malignant tumors and their
      possible function in the nutrient supply may limit the application of the new
      anti-angiogenic therapies.

PMID- 12050755
TI  - [CT based conformal brachytherapy treatment planning]
AB  - PURPOSE: To introduce the CT based three dimensional (3D) conformal brachytherapy
      treatment planning for interstitial implants, to compare the conventional X-ray
      film based planning with the 3D planning from the point of view of reconstruction
      and dosimetry, to discuss the differences and highlight the advantages. MATERIAL
      AND METHODS: On 10 patients with breast and 5 with head and neck tumor treated
      with HDR interstitial implants, following the catheter implantations, CT scans
      were taken at 5 mm spacing. The images were loaded into the PLATO BPS v14.0 3D
      planning system for brachytherapy. The contours of the target volume and critical
      structures were outlined on each slice, the catheter describing points were
      identified and the anatomical structures and catheter positions were
      reconstructed in 3D. Having taken into account the target volume, the active
      lengths were determined in each catheter, and dose optimization on dose points on
      target was performed. RESULTS: The 3D treatment planning was applied at
      interstitial breast treatments and head and neck implants. We investigated the
      dose distribution on axial, reconstructed coronal / sagittal planes and in 3D
      view with respect to anatomical structures. Dose volume histograms related to the
      target volume and critical structures were used for quantitative assessment of
      the plans. We found that the conformal dose distribution might result in increase
      of dose inhomogeneity within the target volume. CONCLUSIONS: The three
      dimensional brachytherapy treatment planning can be introduced into the clinical
      practice under proper technical conditions. A tradeoff between conformality and
      dose homogeneity results in an acceptable dose plan. The dose inhomogeneity can
      be decreased with the use of CT scans taken before the implantation. The
      guidelines and quantitative parameters describing the dose distribution, which
      can be used for determining the optimal dose distribution in clinical point of
      view, are still waiting to be established.

PMID- 12050756
TI  - [Experiences in the treatment of tumour of base of the tongue with high dose rate
      interstitial radiotherapy on the basis of a retrospective analysis]
AB  - PURPOSE: To describe the role, the execution and the importance of interstitial
      radiotherapy in the irradiation of the base of tongue cancer. MATERIAL AND
      METHODS: Between January, 1993 and December, 1998 nineteen patients with primary
      squamous cell cancer of the base of tongue (1 T1N0, 3 T2N0, 2 T3N0, 2 T3N2, 3
      T4N0, 6 T4N1, 2 T4N2) were managed with brachytherapy partly with definitive
      intention combined with teletherapy (60-66 Gy) as a boost, partly as a single
      postoperative treatment. Irradiation was carried out by HDR after-loading (Ir
      192) unit, using rigid needle or flexible plastic catheter. The treatment plan
      was made by PLATO 3D brachytherapy planning system. In case of boost the mean
      total dose of brachyherapy was 22 Gy (12-30 Gy), in postoperative treatment it
      was 27 Gy (24-30 Gy). RESULTS: 6-8 weeks after the definitive radiotherapy the
      CT/MR showed complete remission in 67% and partial remission in 33% of the
      patients. Of all treated patients during the mean follow-up period (30 months)
      the local tumour control was 42%. Five patients (26%) died in local failure. Six
      patients (32%) are alive with tumour. Osteoradionecrosis and fistula did not
      occur. CONCLUSIONS: In the oncological treatment of the advanced base of tongue
      tumour the combination of percutan and interstitial radiotherapy seems to be very
      advantageous,because it improves not only the curability, but the patients'
      quality of life as well.

PMID- 12050757
TI  - [The possible role of information technology in radiotherapy II. The development
      of a biological dose distribution model in the 3-dimensional treatment planning
      of brain tumours]
AB  - OBJECTIVE: Developing a new medical software based on the utilisation of
      information technology required in 3-dimensional treatment planning and modern
      radiotherapy. METHODS: The physical dose distribution programs were converted
      into biological meaning with the insertion of biological equivalence equations
      based on LQ model. Biological dose distributions and biological dose-volume
      histograms were generated. The treatment plans of a brain tumour patient were
      investigated to determine the dose burdening of the normal central nervous system
      tissues. RESULTS: Employing 3D conformal method, the dose of the vital mid-line
      structures decreased significantly, which possesses a more meaningful biological
      importance. Different treatment plans and different fractionation regimens could
      be compared to each other by utilising this kind of biological model. CONCLUSION:
      By employing information technology we succeeded in establishing a theoretical
      biological dose distribution system that could be visualised. The advantages of
      3D treatment planning proved unambiguous. In the future this method will probably
      be suitable to choose the best therapeutic regimens.

PMID- 12050758
TI  - [Dosimetry of total skin electron irradiation]
AB  - Elaboration of such a simple technique for total skin electron irradiation which
      ensures good dose homogeneity and minimal x-ray background dose. MATERIALS AND
      METHODS: We started large electron field irradiations with the Neptun 10p linear
      accelerator in the National Institute of Oncology -Budapest in 1986. After the
      installation of the Siemens Mevatron KD linear accelerator it was possible to
      introduce the modified Stanford technique. This technique satisfies better the
      requirements given in the objective. The required field size of 200x75 cm is
      produced as a result of two fields with 30 degrees angular separation (dual
      field) at a source skin distance of 465 cm. The patient's body is exposed to six
      dual electron fields. The electron energy is 6 MeV. Despite the long source skin
      distance the treatment time is relatively short due to the high dose rate (940
      mu/min) capability of our Mevatron KD. The in air dose profiles were measured in
      miniphantom with semiconductor detector. Depth dose curves were measured in water
      and in polystyrene phantom with semiconductor detector and with films. RESULTS:
      The measured dose homogeneity of the 6 MeV energy dual field with 30 degrees
      angular separation is within +/- 5%in a 200x75cm plane field. The depth of dose
      maximum of the resulting dose distribution of six dual field irradiation is
      between 2 mm and 5 mm, while the depth of 80% isodose curve is about 8 mm. The
      total body x-ray background dose is less than 1% of the skin dose. CONCLUSION:
      The modified Stanford technique adapted to our Mevatron KD linear accelerator is
      suitable for total skin electron beam therapy.

PMID- 12050759
TI  - [Angiosarcomas of the chest wall and breast after radiotherapy: The questions of
      radiogenic origin, diagnosis and treatment]
AB  - PURPOSE: To present medical history of secondary chest wall and breast
      angiosarcomas (AS) developed after radiotherapy, and to discuss the questions of
      radiogenic origin, diagnosis and treatment by the review of the literature.
      METHODS: Report of two cases and MEDLINE search for relevant publications.
      RESULTS: Secondary AS occured in a previously irradiated field after a long (6
      and 8 years) latency period in both cases. Detailed histopathological and
      immunohistochemical examinations from the biopsy and/or surgical specimens
      confirmed the diagnosis as AS. The first patient with moderately differentiated
      AS was treated successfully with radical surgery. The second patient with
      irresecable AS died of rapid local progression within 4 months. The incidence of
      chest wall and breast AS is increased after irradiation, however, controversial
      data exist in the literature. The incidence of chest wall and breast AS after
      radiotherapy was found to be 0.39% in our patient population, which means an
      estimated odds ratio of 2.4 for secondary AS. Stewart-Treves syndrome is not of
      radiogenic origin, since postoperative lymphoedema has been considered as primary
      etiological factor. CONCLUSIONS: Patients treated with surgery and/or
      radiotherapy for primary breast cancer are at higher risk for developing
      secondary AS, compared to the healthy population. An etiological relationship
      between radiotherapy and subsequent AS of chest wall and breast is likely, but
      still controversial. Initial radical surgery is the only effective treatment for
      achieving long term survival. Further adjuvant radiotherapy is no longer
      feasible, due to the previous irradiation. Chemotherapy has only palliative
      effect. These very rare cases deserve special attention due to the atypical
      clinical appearance, difficulties of differential diagnosis and poor prognosis.

PMID- 12050760
TI  - [Preoperative lymphoscintigraphy guided sentinel lymph node biopsy in malignant
      melanoma]
AB  - The authors present preliminary experience with preoperative sentinel lymph node
      biopsy carried out with lymphoscintigraphy in patients with malignant melanoma.
      PATIENTS AND METHODS: In the present study patients operated for primary
      cutaneous malignant melanoma of moderate and high severity were included. On the
      day of surgery isotope labelled colloid was injected intradermally around the
      tumor to indicate the lymphatics and to obtain basic information about the
      localization of the sentinel lymph node(s).During surgery the lymph node(s)
      previously visualized by the injection of patent-blue staining were detected with
      the aid of a gamma probe. Simultaneously, the excision of the primary tumor was
      extended. Histologically verified metastasis in the surgically removed lymph
      node(s) necessitated block dissection possibly within two weeks. RESULTS: The
      distribution of patients (19) according to tumor localisation: 2 - upper
      extremities; 9 - lower extremities; 2 - sacral region; 6 - trunk. Tumor thickness
      ranged from <1.5 mm (6 patients) to 1.5-3 mm (5 patients) and to >3 mm (8
      patients). In two cases the identification of the lymph node has failed. Positive
      sentinel ymph nodes were detected in two patients. It is noteworthy that with one
      patient the sentinel lymph node was not regional but intransit. This study was
      aimed at the development of a suitable method. Further on we wish to try it in
      prospective randomized studies.

PMID- 12050761
TI  - [Stomato-oncological screening test of volunteers]
AB  - OBJECTIVES: Identification and relative incidence of precancerosis and
      malignancies of the head and neck region and in the oral cavity. MATERIAL AND
      METHODS: In three counties of the western region of Hungary we physically
      examined pathological abnormities of healthy volunteers. Computerised examination
      reports and anamnestic data have been registered on data sheets. RESULTS: During
      examination of 5054 persons we have found 5 malignant tumours and 3.7%
      precancerosis (mostly leukoplakia). CONCLUSIONS: Orofacial tumours that are
      constantly increasing in our country account for the necessity of stomato
      oncological screening test. Therefore, screening should be extended as far as
      possible to persons who live in poor social-economical circumstances. Persons
      with multiple risk factors are difficult to be reached by this screening
      test,therefore it is complicated to treat them at an early stage. We have found
      intense ignorance in connection with oral tumours and precancerosis. Oral hygiene
      and status are criticisable. Because of the deficiencies of methods in
      examination the morbidity rate of tumours in oral cavity is undoubtedly higher
      than the rate of the statistical data.

PMID- 12050762
TI  - [Changes of cell mediated immunity in malignant ovarian tumor patients after
      operation]
AB  - OBJECTIVES: The authors discuss upon the changes in the two cell types involved
      in cell mediated immunity (Killer and Natural Killer) as a result of operation in
      malignant ovarian tumor atients. METHODS: They study the preoperative and
      postoperative cell mediated immunity of 28 malignant cystadenocarcinoma cases
      (FIGO stage I/a-III/c). To determine the maximum K and NK cell activity they used
      the kinetic model of cytotoxicity enzyme. RESULTS AND CONCLUSIONS: They conclude
      that operation of malignant ovarian tumors had no significant influence on K and
      NK cell activity. They hypothesize that unchanged cell mediated immunity seems to
      be independent of malignant tumors, especially in these conditions. We need
      further information about this change of cell mediated immunity.

PMID- 12050763
TI  - [Angiocentric T-cell lymphoma]
AB  - SUMMARY: The CD20+ variant of angiocentric T-cell lymphoma is an unusual type of
      T-cell lymphomas that present cystic changes in organs because of ischaemic
      necroses. The purpose of this study was to describe a case of CD20+angiocentric T
      cell lymphoma, discussing its clinical, histopathological and immunohistochemical
      features, to analyze its proliferation kinetics and to consider its possible
      relationship to the Epstein-Barr virus (EBV) to understand better the
      pathobiological nature of the disease. METHODS: The clinical, histopathological,
      immunohistochemical and single-cell DNA cytophotometric features of the case were
      analyzed. In addition in situ hybridization was performed to detect EBV. RESULTS:
      The 24 years old woman was admitted to our Institute because of pain in the
      abdominal region and weight loss. There were enlarged lymph nodes on the neck,
      and biopsy was done. Histological diagnosis: angiocentric T-cell lymphoma, CD20+
      variant. CD3, CD43, CD45RA and CD45R0 antigens were positive in the atypic
      lymphoid cells of the tumour and in cells infiltrating the vascular wall. DNA
      index was 0.8589 (hypodiploid). Tumour cells in G1 phase: 47%, S phase: 45.4%, G2
      phase: 7.6%. Combined chemotherapy was administered because of clinical stadium
      IV/B of malignant lymphoma (5 CHOP-Bleo, CEPP, CEP, CMVE treatment). The disease
      showed gradual progression and the patient died 14 months after the first
      symptoms had appeared. CONCLUSIONS: In the last 13 years there were 5 cases of
      angiocentric T-cell lymphoma at our Institute. The CD20+ variant is rare, its
      clinical symptoms are special, the prognosis is unfavourable. The cause why we
      demonstrate this case is to call attention to a new treatment for these patients
      by immunotherapy using monoclonal antibodies against CD20 antigen.

PMID- 12050764
TI  - [Development of head and neck surgery at the end of the XXth century]
AB  - The development of the surgery of the head and neck tumors seemed to be completed
      for the end of the seventies by the widespread acceptance of the basic
      technologies. However, the discovery of two techniques, medical laser and PM-lobe
      initiated major developments in the surgical oncology of head and neck cancer.
      Based on our studies, the benefits of use of medical laser in oncology are its
      fine-tuned topological preciseness, tissue-protection and the lack of bleeding
      disorders. A special benefit of the medical laser is its ablasticity and the
      support of tissue repair. The wide-spread use of PM-lobe technique in head and
      neck surgery was made it possible by the development of various modifications
      such as the cutan-myocutan and the osteomyocutan ones. By the application of the
      developed variants we were able to correct the consequences of radical resections
      and achieved acceptable functional and esthetic status in cancer patients.

PMID- 12050765
TI  - [Protocols for comprehensive diagnosis and treatment of breast cancer]

PMID- 12050766
TI  - [Expression of HER2 in breast cancer]
AB  - In breast cancer the membrane expression of HER2 receptor protein encoded by the
      HER2 proto-oncogene seems to have an ever growing clinical significance. In
      tissue cultures and animal experiments it was shown that the HER2 gene
      amplification induces malignant transformation and intensifies the aggressiveness
      of the tumour cells. Correlating with the so called pheno-and genotypic
      prognostic markers, the overexpression of HER2 in breast cancer predicts also
      poor prognosis and indicates enhanced potential for metastatisation. In some of
      the so called precancerous proliferations and "in situ" carcinomas we
      demonstrated the enhanced membrane staining of the HER2 receptor protein. In
      these cases we frequently observed DNA aneuploidy,the presence of p53 mutational
      protein and CD44v6 glycoprotein. The immunohistochemical studies of HER2 protein
      in invasive carcinomas have revealed, an interrelationship between the grade of
      differentiation, histological type, aggressiveness and biological behaviour of
      the "in situ" and invasive carcinomas. In clinical studies trastuzumab, a
      humanized monoclonal antibody recognizing extracellular domain of HER2 receptor
      protein, has proved to be effective in HER2 overexpressing metastatic breast
      cancer either as monotherapy or in combination with chemotherapeutical agents.
      The DAKO "HercepTest" is a semiquantitative, standardised method for the
      determination of HER2 overexpression.

PMID- 12050768
TI  - [Clodronat therapy of hypercalcaemia associated with male breast cancer]
AB  - OBJECTIVES: The aim of this study is to survey the treatment of bone metastases
      and hypercalcaemia. MATERIALS AND METHODS: A case of male breast cancer is
      presented here by the authors. The applied clodronat therapy was beneficial.
      RESULTS: The diagnostic difficulties of such rare, unusually localised,
      metastasizing male breast cancer are discussed with the survey of Hungarian and
      world literature. CONCLUSION: The bisphosphonates - beside treating the
      hypercalcaemia caused by bone metastasis - provide a better quality of life.

PMID- 12050767
TI  - [Prognostic factors of breast cancer]
AB  - OBJECTIVES: Characterization of breast cancers by various tumour markers which
      are appropriate for the identification of high risk groups. Markers related to
      the metastasis cascade and tumour recurrence have been investigated. MATERIALS
      AND METHODS: RT-PCR was used to determine the expression of cytokeratin 20 in the
      bone marrow and sentinel lymph node of breast cancer patients (n=45). The
      expression of HER2, Cadherin E, Cyclin D, Bcl2 and Bax has been evaluated by
      Western blot (n=744 invasive ductal carcinomas and 117 invasive lobular
      carcinomas, 124 recurrent breast cancers). Mutations of p53, APC and beta Catenin
      genes were detected by PCR-SSCP method. RESULTS: Expression of cytokeratin 20 was
      found in 30% of the bone marrow samples indicating the presence of
      micrometastasis. The level of Cyclin D, HER2 and Bcl2 is elevated four-fold in
      the recurrent breast cancers. The metastasis of invasive ductal carcinomas is
      accompained by high frequency of p53 mutations (24%) and APC mutations (18%). The
      invasive lobular carcinomas could be characterized with low frequency of p53
      mutation (3%), low level of Cadherin E and high level of catenin beta.
      CONCLUSIONS: Identification of micrometastasis can promote the development of
      therapeutic strategy. Evaluation of HER2 level and determination of p53 mutations
      contribute to the identification of high risk patients. Our results suggest that
      the progression of invasive ductal carcinomas depends on the APC mutations, while
      metastasis of invasive lobular carcinomas depends on beta catenin mutations.

PMID- 12050769
TI  - [Tumour markers in human breast cyst fluid in gross cystic breast disease (GCBD)]
AB  - AIM: Parallel measurements of tumour markers in the serum and breast cyst fluid
      in a high risk group (GCBD) of breast cancer. The identification of individuals
      belonging to this group and their follow-up. MATERIALS AND METHODS: In the breast
      cyst fluid of 108 patients with GCBD (mean age 47 years) we measured the levels
      of CA 15-3, TPA, CEA and beta HCG completed by PCT determinations.
      Simultaneously, the serum CA 15-3 and TPA concentrations were also measured using
      the Luminescent Immunoassay techniques. RESULTS: Strikingly high TPA values were
      found in 98% of the patients. The CA 15-3 levels, however, were pathological only
      in 24%of them. The CEA and beta HCG levels showed hardly any rise and the PCT
      concentration remained normal. CONCLUSIONS: The lack of any rise in PCT
      concentration precludes the inflammatory origin of the cystic fluid and the
      normal serum arker levels exclude ultrafiltration. The increased TPA
      concentration in the breast cystic fluid and the occurrence of pathological CA 15
      3 level in the above percentage of the cases suggest that GCBD represents not
      only a high risk group but possibly a precancerous state, too.

PMID- 12050770
TI  - [Role of Iphosphamide in the treatment of breast cancer]
AB  - Breast cancer is the most frequent solid tumor in women. Predictive and
      prognostic factors play an important role in the treatment of this cancer. We
      focused on high risk and heavily pre-treated metastatic breast cancer patients,
      trying to find the best combination of cytotoxic drugs with high efficacy and low
      toxicity. Ifosfamide is chemically related to nitrogen mustard and is a synthetic
      analogue of cyclophosphamide. Ifosfamide has a wide range of antitumor activity.
      Since ifosfamide as monotherapy has introduced significant tumor reduction in
      1(st) line chemotherapy for advanced breast cancer, some studies started with
      high-dose continuous infusion of ifosfamide,or combined with paclitaxel or
      vinorelbine. Patients with poor prognosis primary breast cancer treated with high
      dose chemotherapy supported by peripheral blood progenitor cell (PBSC)
      transplantation have lower risk for local relapse and longer disease-free
      survival. Ifosfamide working in the mobilization regimen has effective anti-tumor
      activity while mobilizing sufficient PBPCs in the majority of patients. In
      combination with other cytotoxics showed to be effective in high-dose protocols.

PMID- 12050771
TI  - [Taxotere phase III trial on the first-line treatment of metastatic breast
      cancer]
AB  - OBJECTIVES: Doxorubicin and taxanes are the most effective agents in the
      treatment of advanced breast cancer. The aim of the study was to compare the
      efficacy of Doxorubicin (A) + Docetaxel (T) (AT) and standard Doxorubicin (A) +
      Cyclophosphamide (C) (AC) chemotherapy. MATERIALS AND METHODS: Results of first
      line AT (50/75 mg/m2) and AC (60/600 mg/m2) D 1 q 3 wk, maximum of 8 cycles, were
      compared. Three Hungarian centers - Petz Aladar County Teaching Hospital, Gyor,
      St.Margit Hospital, Budapest, and BAZ County Hospital, Miskolc, with 33 patients
      participated the international, phase III randomized TAX 306 trial. Between June,
      1996 and March, 1998, 429 metastatic breast cancer patients were enrolled in the
      study. Eligible patients were who had not received prior chemotherapy for
      advanced disease, and were anthracycline-naive. Objective response rate observed
      in the AT arm was significantly higher than in the AC arm (ORR: 60% vs. 47%,
      p=0.008). Time to progression was longer in the AT group (37.1 weeks vs. 31.9
      weeks, p=0.0153). Except for higher incidence of neutropenia not requiring dose
      modification in the AT arm, there were no major differences concerning toxicity.
      T did not enhance cardiac toxicity induced by A. CONCLUSION: AT results in
      significantly higher response rate and longer time to progression than AC in
      advanced breast cancer, even in patients with unfavourable prognosis.

PMID- 12050772
TI  - [Chemotherapy of breast cancer: focus on paclitaxel]
AB  - Paclitaxel is among the most effective agents in the treatment of breast cancer.
      Both as a single agent and in combinations, paclitaxel is effective as first-line
      therapy and as a salvage therapy in patients with locally advanced or metastatic
      disease. Paclitaxel also demonstrated efficacy in patients who received prior
      anthracyclin therapy and those with anthracyclin-resistant disease. In the
      adjuvant setting, data from randomized study have supported the sequential use of
      paclitaxel after therapy with doxorubicin / cyclophosphamide for patients with
      node-positive disease. The drug may be used in combination with other
      chemotherapeutical agents and immune stymulatory agents. Therapy on weekly and
      every-three-week schedules has been effective.

PMID- 12050773
TI  - [Aromatase inhibitors and inactivators in the treatment of advanced breast
      cancer]
AB  - Advanced breast cancer remains incurable. For these patients, durable response
      and minimal toxicity are the main goals of current therapy. The antiestrogen
      tamoxifen has proved to be a significant advance in the treatment of breast
      cancer. Due to its partial estrogen activity, long term medication with tamoxifen
      has been found to cause endometrium proliferation wich can result in cancer in
      some patients. Reduction of estrogen production identified the aromatase
      inhibitors. Both steroidal substrate analog, type I inactivator, wich inactivate
      the enzyme and non-steroidal competitive reversible, type II inhibitors, are now
      avaiable. Two new 3(rd) generation aromatase inactivators have recently completed
      phase III evaluation (anastrozole and letrozole) and we have some results
      investigating one of the new 3(rd) generation aromatase inhibitors (exemestane).
      The 3(rd) generation aromatase inhibitors and inactivators are better tolerated
      and more effective than each of our current standard 2(nd) line endocrin
      therapies. These agents are being directly compared with standard adjuvant
      medication, tamoxifen, or are being evaluated in different sequences.

PMID- 12050774
TI  - Cryosurgery - a review of recent advances and current issues.
AB  - Advances in cryosurgery since 1990 were initiated by the development of improved
      cryosurgical equipment and by the availability of intraoperative ultrasound to
      monitor the tissue-freezing process. Interest in research on the effects of
      freezing on tissue and on new clinical applications was then stimulated. The
      research led to a better understanding of the mechanisms of cryogenic injury,
      including cell death by apoptosis, which has emerged as a potential key to the
      use of adjunctive chemotherapy in the treatment of cancer. Optimization of
      cryosurgical technique will also improve clinical results.

PMID- 12050775
TI  - Glass transition and enthalpy relaxation of polyphosphate compounds.
AB  - The glass transition behaviour of polyphosphate compounds such as di- and tri-
      polyphosphates used as food additives and ATP, ADP existing in biosystems, were
      investigated by using DSC. From the DSC heating curves of the frozen solutions,
      the glass transition temperatures of the maximum freeze concentrated solutions,
      Tg', were determined. It was found that Tg's for polyphosphates are relatively
      high. The lyophilized tripolyphosphates, ATP and ADP also showed the glass
      transition at a relatively high temperature, depending on the moisture content.
      In addition, the enthalpy relaxation behaviour of glassy ATP and ADP was examined
      and analyzed by using the Kohlrausch-Williams-Watts (KWW) and the Vogel-Fulcher
      Tammann (VFT) equations. Judging from the parameters of the KWW and VFT
      equations, the amorphous states of ATP and ADP were suggested to be more fragile
      than trehalose and sucrose.

PMID- 12050776
TI  - Ice structuring proteins - a new name for antifreeze proteins.
AB  - Antifreeze proteins (AFPs) have been reported in the academic literature for many
      years, and are increasingly arousing interest in the technical and popular media,
      particularly because of their potential applications. However, the term
      "antifreeze" does not always accurately describe their natural function, or their
      application in frozen systems, where they do not prevent freezing, but control
      the size, shape and aggregation of ice crystals. We survey the properties and
      applications of AFPs and propose a more generally applicable name based on the
      fact that all AFPs bind to ice and consequently influence crystal growth and
      interactions: "Ice Structuring Proteins".

PMID- 12050777
TI  - Vitrification of human spermatozoa without cryoprotectants.
AB  - The aim of our study was to investigate the effects of vitrification (cooling
      rate approximately 10000(C/min) without cryoprotectants on swim-up prepared human
      spermatozoa in comparison to standard conventional freezing with cryoprotectants.
      Motility, morphology, rate of viability and acrosome reaction of spermatozoa were
      evaluated. The described method of cryopreservation of human spermatozoa by
      direct plunging into liquid nitrogen slush without cryoprotectants was effective
      and could be recommended for routine IVF.

PMID- 12050778
TI  - Sucrose incubation increases freezing tolerance of asparagus (Asparagus
      officinalis L.) embryogenic cell suspensions.
AB  - The freezing tolerance of asparagus (Asparagus officinalis L.) embryogenic cells,
      as determined by electrolyte leakage, was increased by the incubation of samples
      in medium containing 0.8 M sucrose. To elucidate the mechanism involved, we
      investigated the changes in soluble carbohydrates, cell ultrastructure and
      proteins accompanying the increase in freezing tolerance following incubation in
      sugar-rich medium. During sugar incubation, the intracellular sucrose content
      increased from 67  mol g-1FW to 429  mol g-1FW; it was also metabolized into
      fructose and glucose, as determined by high-performance liquid chromatography.
      Microscopy revealed that sugar incubation induced plasmolysis of embryogenic
      cells and drastic changes in cell ultrastructure with the appearance of rough
      endoplasmic reticulum (rER). Furthermore, immunoblotting analysis with anti
      dehydrin antiserum revealed that a dehydrin-like protein appeared only when
      maximal freezing tolerance was induced by sugar incubation. These results suggest
      that freezing tolerance of asparagus embryogenic cells is increased by a complex
      mechanism involving notably changes in cell ultrastructure and accumulation of
      certain sugars and proteins during sugar incubation.

PMID- 12050779
TI  - A simple GC method for determination of cryoprotector diols 1,4-butanediol or 2,3
      butanediol in isolated rat hepatocytes.
AB  - We devised a simple method for determining the cryoprotectant agents 1,4
      butanediol or 2,3-butanediol in isolated rat hepatocytes. After extraction of of
      hepatocytes with water (containing internal standard - ethylene glycol 1.25
      mg/mL) the diol content was analyzed by gas chromatography. The method shows a
      linear response in the range 0.125 to 2.50 mg/mL for 1,4-butanediol and 0.25 to
      3.75 mg/mL for 2,3-butanediol. The accuracy and precision of the method were
      evaluated and the coefficients of variation were found to be within = 6.0 %. The
      recoveries from hepatocyte samples containing 0.50, 1.00 and 2.00 mg/mL were 91.0
      to 108 % for 1,4-butanediol and 80.6 to 100.3 % for 2,3-butanediol, respectively.
      This method allowed the determination of the intracellular concentration of diols
      in hepatocytes preserved for up to 120 hours at - 4 (C in UW solution + 8 % w/v
      1,4-butanediol (or 2,3-butanediol).

PMID- 12050780
TI  - The effect of saccharides on the post-thaw recovery of cane toad (Bufo marinus)
      spermatozoa.
AB  - The effect of monosaccharides (glucose, fructose) and disaccharides (maltose,
      sucrose, trehalose) as diluents, in cryoprotective additives containing 15% (v/v)
      DMSO or glycerol as cryoprotectants, were investigated on the recovery of sperm
      motility after cryopreservation of cane toad (Bufo marinus) spermatoazoa at low
      (approximately 5 degrees C/min(-1)) and high cooling rates (approximately 35
      degrees C/min(-1)). The results show that: 1. recovery of percentage motility was
      higher with slow cooling than with high cooling rates (37.0 +/- 2.5%, 15.3 +/-
      1.6%, P<0.001, respectively), 2. disaccharides were more effective than
      monosaccharides in protecting spermatozoa with slow cooling (43.9 +/- 1.2%, 26.8
      +/- 2.5%, P<0.02, respectively), 3. glycerol was more effective than DMSO with
      fast cooling (18.3 +/- 2.2%, 12.6 +/- 2.3%, P<0.02, respectively), 4. trehalose
      with glycerol was the most effective cryoprotective additive with fast cooling
      (31.0 +/- 3.2%, P<0.05), and 5. overall the recovery of degree (vigour) of
      motility (range, 1.9 - 3.2) was more resilient to cryopreservation than recovery
      of percentage motility (range, 8.9 - 51.5 %). Comparison of post-thaw percentage
      and vigour of sperm motility up to 24 minutes after activation showed
      disaccharides supported greater duration sperm motility than monosaccharides This
      result and the recovery of spermatozoa immediately after freeze-thaw, show the
      main effect of saccharides are as cryoprotectants and not as exogenous energy
      substrates.

PMID- 12050781
TI  - The short-term storage and cryopreservation of spermatozoa from hylid and
      myobatrachid frogs.
AB  - The short-term storage (at 0 degrees C) and cryopreservation of spermatozoa may
      be useful for providing gametes for fertilisations performed in programmes for
      the conservation and management of endangered amphibians. The current study was
      undertaken to examine the applicability of amphibian spermatozoa storage
      protocols developed with the cane toad (Bufo marinus) to a wider range of
      amphibian species, with a view to ultimately using these protocols for endangered
      species. In Australia, at least 29 species of recently extinct or endangered
      frogs are from the families the Myobatrachidae and the Hylidae. This study
      investigated the applicability of short-term storage and cryopreservation
      protocols developed for cane toad (Bufo marinus) spermatozoa to those of hylid
      and myobatrachid species. Storage of spermatozoa in intact testes or in
      suspensions for six days at 0 degrees C showed spermatozoa maintained higher
      motility in suspensions than those in testes, and hylid spermatozoa maintained
      greater motility than myobatrachid spermatozoa. However, the protocols for
      optimal storage at 0 degrees C varied with testis size when spermatozoa were
      stored in whole testes. Spermatozoa from 13 frog species representing both
      families were cryopreserved using sucrose as diluent with Me(2)SO or glycerol as
      cryoprotectants. After cryopreservation hylid spermatozoa showed a greater
      recovery than myobatrachid spermatozoa and Me(2)SO provided higher recovery than
      glycerol. The freeze-thaw recovery of spermatozoa was independent of testes
      weight of the species studied. These results show spermatozoa from the Hylidae
      and Myobatrachidae may be stored both in the short-term (at 0 degrees C) and long
      term by cryopreservation using protocols established for B. marinus.

PMID- 12050782
TI  - Using Lab On-line to Clone and Identify the Esophageal Cancer Related Gene 4.
AB  - Using Internet as platform, databases as materials and software as tools to
      assemble a lab on-line is revolutionizing in bioscience research. The major works
      of lab on-line are cloning, identification, localization of genes, and the
      structural and functional analysis of proteins. In this report, the esophageal
      cancer related gene 4(ECRG-4)(accession number AF325503) was successfully
      isolated. The 97 bp ECRG-4 EST was initiallyusedto fish the human EST databases.
      Five pieces of ESTs showed strong homology to it, and they were assembled to one
      772 bp cDNA sequence by DNASTAR software. Then the 447 bp full open reading frame
      of ECRG-4 was determined by ORF FINDER to encode 148 amino acids. Sequence of
      ECRG-4 did not reveal remarkable similarity to the known sequences in a homology
      analysis with the public database of GenBank, showing that it is a new gene.
      Homology analysis of protein coding by ECRG-4 showed a 31% homology with mouse
      IgG V region. ECRG-4 gene is expressed in normal esophagus, bladder and brain
      tissues, but its expression was significantly down-regulated in prostate tumors
      and tumor cell lines. ECRG-4 gene was located in 2q14.1--4.3 by HTGS and STS, and
      was conformed by radiation hybrid (RH) method. We propose that this purely lab on
      line cloning approach can be used by modestly sized laboratories to rapidly and
      accurately characterize human genes without wasting too much money and time.

PMID- 12050783
TI  - Hypochlorite and Cu(2 ) Induced Oxidation of High Density Lipoprotein.
AB  - In order to further study on the properties of oxidatively modified high density
      lipoproteins(Ox-HDL), the effects of hypochlorite and Cu(2 ) on HDL oxidation in
      vitro were investigated. The results showed that, as to LDL, HDL was also
      oxidized by hypochlorite and Cu(2 ), causing the formation of thiobarbituric acid
      substances (TBARS) and increase of negative charges on HDL particle surface. It
      was also found that during the oxidation of hypochlorite, both apoAI and apoAII
      were degraded into small fragments, the phosphatidylcholine(PC) hydrolyzed into
      lysophosphatidylcholine (LPC) and the protein components of HDL formed carbonyls.

PMID- 12050784
TI  - The Spot Fitting and Expression Quantification for the Nylon Filter cDNA
      Microarray.
AB  - High-density cDNA microarray is important in monitoring large scalegenomic
      expression profile. With radiolabeled cDNA sample, nylon filter cDNA microarrays
      have high sensitivity and wide linear range of hybridization signals, so it can
      be employed to detect many important low-abundance cDNAs. However, the nylon
      filter tends to be randomly contaminated, and the array spots are prone to
      dispersion and saturation, resulting in inaccurate expression value. Based on
      aphysical model, we address a novel treatment with accurate positioning,
      complement of saturation and correction of interference. Thus the accurate
      quantificati on of expression can be extracted with remarkably improved
      reproducibility.

PMID- 12050785
TI  - Expression of Colonization Factor Antigen I of Enterotoxigenic Escherichia coli
      in Shigella flexneri 2a T32.
AB  - A host-plasmid lethal balancing system was constructed based on asd gene in an
      avirulent strain of S.flexneri to express colonization factor antigen I(CFA-I) of
      enterotoxigenic Escherichia coli.The results of Western blotting suggested that
      avirulant strain of S.flexneri Fwl01 expressed CFA-I steadily. Examination of
      negatively-stained preparation of cultures by electron microscopy showed that
      S.flexneri Fwl01 carrying the plasmid pZHY21 had thick pili on its surface.
      Antibodies against CFA-I were decteted in sera of mice immunized with recombinant
      bacteria either orogastrically (o.g.) or intranasally(i.n.); simultaneously sIgA
      against CFA-I was also decteted in the intestine. This work is helpful for
      constructing multivalent reombinant vaccine for prevention of bacterial diarrhea.

PMID- 12050786
TI  - Cloning and Expression of Targeting CuZn-SOD to Central Nervous System.
AB  - Oxygen-derived free radicals are thought to be involved in the pathogenesis of a
      wide range of neurological disorders. Targeted delivery of CuZn-SOD to neurons in
      central nervous system may have therapeutic value in such diseases. The gene
      encoding human CuZn-SOD was fused to tetanus toxin fragment C geneto construct a
      fusion gene, then it was cloned into prokaryotic expression vector pET-22b( ) and
      baculovirus vector pFastBacHTb, and was expressed in E.coli and Tn-5B1-4 cells,
      respectively. The recombinant fusion protein has a subunit molecular mass of 68
      kD and is recognized by both anti-CuZn-SOD and anti-tetanustoxin antibody. By
      pyrogallol autooxidation assay, it is shown that the CuZn-SOD moiety retains
      substantial enzymatic activity, where the TTC moiety might deliver the fusion
      protein to neurons in central nervous system. So, CuZn-SOD/TTC may be a useful
      agent for the targeted delivery of CuZn-SOD to neurons.

PMID- 12050787
TI  - Structure and Function of a Novel Silencer in 5' Flanking Distal Region of Human
      beta Globin Gene.
AB  - A novel silencer fragment(310 bp) was recently discovered and identified to
      locate between -2 132 bp and -1 822 bp upstream from the cap site of beta-globin
      gene by gel retardation assay and luciferase reporter gene expression analysis.
      DNA footprinting assays were performed to determine the interaction between its
      DNA sequence and binding proteins from the nuclear extract of Hela cells. The
      results showed that there were two nuclear protein binding sites in thissilencer,
      one was the -2 017--2 011 bp sequence CTTCCGC" and the other was the -2 006--1
      997 bp sequence "CACTTTATTT". Two sequences were mutated into "CTTAAGC" and
      "CACTTAAGTT", respectively by two mutagenic primer pairs, in order to construct
      two mutation types of the 310 bp fragment. The competitive gel retardation assays
      showed that two mutation types of the 310 bp fragment and their four smaller DNA
      fragments, which were formed respectively by the digestion of restriction enzyme
      BspTI, all lost their competitive ability against the wild type of 310 bp
      fragment probe for DNA-binding proteins without exception. Furthermore, the
      double-strand oligonucleotides, which contained both the sequences of "CTTCCGC"
      and "CACTTTATTT", were synthesized, and the competitive gel retardation assays
      showed that they competed ability against wild type 310 bp fragment probe for DNA
      binding proteins. The results suggest that two binding sites of the nuclear
      proteins are involved or associated with a potential DNA-DNA interaction.
      Moreover, the specific DNA-binding proteins were purified from the nuclear
      extract of Hela cells by using "DNA-binding protein purification kit" for
      magnetic isolation. In order to identify the purified DNA-binding proteins, a SDS
      PAGE was performed. By using the silver staining, the PAGE electrophoretogram
      showed that these two nuclear proteins specifically bound to these two sites of
      the silencer, appearing as two definite bands. The molecular weight of each
      protein was determined to be 37 kD or 81 kD, respectively.

PMID- 12050788
TI  - Expression of Human Angiostatin in Pichia pastoris and the Detection of Its Anti
      angiogenic Activity.
AB  - Human angiostatin cDNA was amplified from human hepatoma cell line HepG2 using RT
      PCR and was cloned into pPIC9K vector. Recombinant Pichia pastoris strain with 4
      copies of angiostatin gene was obtained. Recombinant protein was purified by
      lysine-affinity Sepharose column and the finally purified angiostatin was 25
      mg/L, higher than previously reported 17 mg/L. Amino acid sequence analysis
      revealed the identity of our protein the same with that previously reported.
      Recombinant angiostatin inhibited specifically the proliferation of bovine aortic
      endothelial cell stimulated by bFGF, with ED(50) being about 3 mg/L.

PMID- 12050789
TI  - Construction of a Novel Engineering Strain E.coli G830,which is Adoptable to High
      cell-density Fermentation.
AB  - A novel engineered strain G830 adoptable to high-cell-density fermentation by
      integrating bacterial hemoglobin vhb (Vitreoscilla hemoglobin gene) into thr
      operon in the chromosome of PA1 blocking Pta-Ack metabolic pathway through the
      homologous recombination between the homologous fragments of integrated plasmid
      and that of chromosome. The engineered strain G830 was characterized by phenotype
      observation, PCR, thr mutant, acetate acid detection, Western blotting and VHb
      activity assays. In high dentity fermentation, the cellular respiration, energy
      metabolism, highest bacterial density and dry bacteria weight of the G830 strain
      were markedly better than control strains PA1 and BL21. The expression of
      recombinant prolyl endopeptidase (PEP) in G830 and PA1 under the above condition
      was high and stable. Their growth situation and fermentation parameters were
      similar with their parental strains without plasmids, and resided plasmids
      maintained stably in those strains. It revealed that the integral VHb and acetate
      metabolism pathway (Pta-Ack) block improved the growth of host strain under low
      dissolved-oxygen conditions, enhanced the recombinant proteins production and
      reduced the accumulation of acetate harmful to bacterial growth. In conclusion,
      the novel engineering strain G830 was adoptable to high cell density
      fermentation.

PMID- 12050790
TI  - Cloning, Expression and Antibody Production of the Disintegrin Domain of Human
      Fertilin beta.
AB  - A cDNA for the disintegrin domain (hf279) was isolated by PCR from human testis
      cDNAs. DNA sequencing indicated that hf279 cDNA encoded 93 amino acid residues,
      and it was identical with the reported sequence of fertilin beta. An expression
      plasmid, pGEX hf279, was constructed by inserting hf279 cDNA into plasmid pGEX-4T
      2 containing gst gene. The expression plasmid was introduced into E.coli
      BL21(DE3) cells and a substantial amount of soluble fused protein GST-HF93 was
      obtained by the expression strain HF93/BL21 induced with IPTG. SDS-PAGE analysis
      revealed that the GST-HF93 fusion protein had an apparent molecular weight of 38
      kD and accumulated up to 50% of bacterial soluble proteins. The fusion protein
      was purified by glutathione S-transferase (GST) Sepharose 4B column (purity 90%)
      and digested by thrombin to obtain the purified HF93 peptide (purity 80%).
      Polyclonal antibodies were obtained from the serum of miceimmunized with purified
      HF93 which was isolated by GST Sepharose 4B column and SDS-PAGE. ELISA and
      Western blot analysis showed its specificity to HF93. Therefore this antibody can
      be used in further studies on the function of HF93.

PMID- 12050791
TI  - The Influence of FEN-1 Gene on Cell Cycle and Genetic Stability.
AB  - FEN-1 is essential in the cell replication, repair and in the maintenance of
      cellular genetic stability. In this report, it was verfied that FEN-1 antisense
      mRNA fragment was expressed in the cell line FL-FEN-1(-),constructed in our lab,
      blocking FEN-1 gene expression. It was found by the flow cytometer analysis that
      the cell cycle of FL-FEN-1(-) cells was delayed in the S-phase DNA synthesis
      process and arrested in G(1) phase. In a mutation assay, based on the shuttle
      plasmid pZ189, the spontaneous mutation frequency of SupF tRNA gene in the
      plasmid in the FL-FEN-1(-) cells was 19.1x10(4),while it was 2.9x10(4) and
      3.0x10(4) in the control cells FL and FL-M, respectively. Further study showed
      that nontargeted mutation frequency of the FL-FEN-1(-) cell induced by MNNG was
      almost the same as the control, indicating that the mutants derived from the
      block of FEN-1 gene and the nontargeted mutants may be formed through different
      passways. The FL-FEN-1(-) cells exhibit increased sensitivity to alkylating agent
      MNNG.

PMID- 12050792
TI  - Cloning and Expression Analysis of a Laryngeal Carcinoma Related Gene, LCRG1.
AB  - By screening a human adult cDNA library using a cDNA fragment (AF10056) as a
      probe, which is significantly down-regulated in laryngeal carcinoma and
      represents a novel gene, a cDNA, LCRG1(laryngeal carcinoma related gene 1) was
      identified, which was significantly down-regulated in 12 of 30(40%) primary
      laryngeal carcinomas and in 6 of 11(54.5%) various cancer cell lines. This gene,
      localized on chromosome band 17q12--21.1 by alignment of it with STS markers, was
      composed of six exons and spaned about 60 kb of genomic DNA with a 3.4 kb mature
      transcript. The putative protein encoded by this gene was 288 amino acid with no
      significant homology with any known proteins in databases. LCRG1 was expressed in
      many tissues, as shown by MTN blot analysis. These data suggest that LCRG1 is
      related to the laryngeal carcinoma.

PMID- 12050793
TI  - Isolation and Characterization of the PA28-associated Proteasome.
AB  - Proteasome, a high molecular weight multicatalytic protease complex,is
      responsible for most non-lysosomal intracellular protein degradations. The
      proteasome is composed of a 20 S catalytic core (20 S proteasome) and additional
      subunits, that are thought to be involved in the recognition of proteins or in
      the regulation of the protease activity of the proteasome. A 180 kD activator,
      named PA28 or Reg, associates with the 20 S proteasome and enhance the peptidase
      activity of the 20 S core enzyme. In this report, the biochemical isolation of
      the PA28-associated proteasome subset from the 20 S proteasome core is described,
      based on gradient anion exchange chromatography. The PA28-20 S proteasome subset,
      isolated from EBV-transformed B cells, was found to be highly enriched in the
      LMP2 (low molecular weight protein) subset, whereas no LMP2 was detected by
      immunoblotting in the PA28-20 S proteasome subset. The close correlation of
      expression of PA28 and LMP2, two interferon (IFN)-gamma inducible proteasome
      components,on a single proteasome subset suggests that PA28 may associate
      preferentially with LMP2-containing proteasomes, and/or this subset may have a
      specific role in the processing of environmental antigens.

PMID- 12050794
TI  - Expression, Purification and Biological Activity Analysis of Human Vascular
      Endothelial Growth Factor (VEGF(165)) in Pichia pastoris.
AB  - The human VEGF(165) cDNA was amplified by PCR, and was inserted, after confirming
      by DNA sequence analysis, into the Pichia pastoris expression vector pPIC9K
      containing AOX1 promoter and lead sequence of alpha factor gene to form a
      recombinant expression plasmids pPIC9K/hVEGF(165). This recombinant plasmid was
      transformed into KM71. Transformants were screened, cultured inflasks and induced
      by the addition of 1% methanol. After 4 days of methanol induction, the expressed
      hVEGF(165) came up to 60% of total proteins in medium supernatant as shown by SDS
      PAGE. Western blot assay proved that the expressed hVEGF(165) had good
      antigenicity and high specificity. The recombinant protein was further purified
      by using Heparin-Sepharose CL6B affinity chromatography, and was proved that it
      had good biological activity to stimulate HUVEC proliferation and to promote
      collateral blood vessel formation in an acquired limb artery occlusion animal
      model.

PMID- 12050795
TI  - Improvement of Bacterial Two Hybrid System.
AB  - Bacterial two-hybrid system is a newly developed method for studying protein
      protein interactions, especially for effects of the environmental factors on the
      interaction. In our studies of the effect of NH(4)( ) or oxygen on the NifL-NifA
      interaction, it was found that E.coli strain DHP1 cya(-), when transformed by T18
      NifL together with T25-NifA, exhibited high activity of beta-galactosidase in the
      presence of NH(4)( ), and appeared as red colonies when grown in
      MacConkey/maltose agar. This indicated the direct interaction of NifL and NifA.
      However,similar phenomena were also shown in the case of the DHP1 cya(-) strain
      harboring T18-NifL or T25-NifL alone, respectively, without its interacting
      counterpart T25-NifA or T18-NifA. In this paper, a brief method is presented to
      detect the protein-protein interaction using direct assay of the adenylate
      cyclase, thus minimizing the false positives produced by the beta-galactosidase
      activity assay or MacConkey/maltose agar plating.

PMID- 12050796
TI  - Phages Displaying Peptides with beta Turn Conformation.
AB  - Peptide CX(2)GPX(4)C, which was supposed to adopt a typical beta turn
      conformation, was displayed on the surface of filamentous phages by fusing to the
      N-terminus of minor coat protein g3p. The diversity of this library was
      1.04x10(8). Sequences from 19 randomly selected phage clones indicated that the
      distribution of nucleotides and amino acids paralleled the expected frequency.
      The combined index of hydropathy and isoelectric point of these 19 peptides were
      randomly distributed over wide ranges. The enrichment was obtained after 3 rounds
      of screening with monoclonal antibody 12CA5. And the results of phage ELISA and
      competitive ELISA showed that the 15 individual phage clones randomly selected
      from the third round elution specifically bound to the antigen-binding site of
      the antibody. This binding was abolished after destroying of the conformation.

PMID- 12050797
TI  - Cloning and Sequence Analysis of cDNAs Encoding Two Acidic PLA(2) from venom of
      Ophiophagus hannah(King Cobra), Guangxi Species.
AB  - Total RNA was extracted from venom glands of Ophiophagus hannah, Guangxi species.
      The cDNAs encoding PLA(2) were amplified by RT-PCR and cloned into the PUCm-T
      vector. The positive clones encoding two acidic PLA(2) (APLA(2)-1 and APLA(2)-2)
      were selected and bidirectionally sequenced. Their complete amino acid sequences
      were deduced and found to be identical to the known amino acid sequences. Their
      isoelectric points calculated by computer agreed with the values determined with
      their protein. Homology analysis indicated that the mature peptide of APLA(2)-1
      had high homology with PLA(2) from venoms of Ophiophagus hannah, Fujian and
      Taiwan species, but APLA(2)-2 had lower homology. The most striking difference
      between APLA(2)-2 and other PLA(2) from Ophiophagus hannah venoms is the missing
      of a extra "pancreatic loop" at residues 62--66 in APLA(2)-2, and it may be
      related to their species evolution and biological activity.

PMID- 12050799
TI  - Purification and Characterization of AAVP, a Protein Inhibitor of TMV Infection,
      from the Edible Fungus, Agrocybe aegerita.
AB  - A protein with activity of inhibiting TMV infection on Nicotiana glutinosa, named
      AAVP, was isolated and purified from the fruiting bodies of edible fungus
      Agrocybe aegerita by precipitation of 40%--80% saturation of (NH(4))(2)SO(4)
      followed by DEAE-Fast Flow and S-200 column chromatography. The protein was
      proved to be homogeneous by SDS-PAGE and IEF. Analysis of the composition of
      amino acids showed that this protein contained no cysteine, poor in methionine
      and phenylalanine and rich in acidic and hydroxyl amino acids. The inhibition of
      TMV was 84.32% when the concentration of AAVP was 200 mg/L. N-terminus of this
      protein was blocked by pyroglutamyl, and the N-terminal sequence was
      QGVNIYNIVAGA. On potato-sucrose-agar medium, the purified protein did not inhibit
      the growth of three plant pathogen fungi, Trichoderma viride, Colletotrichum
      musae and Fusarium oxysporum.

PMID- 12050798
TI  - Diversity of PLA(2) Genes from Sea Snake Lapemis hardwickii Gray Venom.
AB  - Three full-length cDNA from Lapemis hardwickii Gray, (namely PLA(2)-8, PLA(2)-9
      and PLA(2)-384), encoding phospholipase A(2) (PLA(2)), were isolated and
      sequenced. These cDNA sequences were composed of 456 bp, 438 bp and 438 bp,
      encoding a signal peptide of 27 amino acids and a mature peptide of 125, 119 and
      119 amino acids, respectively. The analysis results by computer indicated PLA(2)
      8, PLA(2)-9and PLA(2)-384 has a pI of ca. 4.8, 7.8 and 8.4, respectively.
      Sequence analysis of amino acid and prediction of secondary structure suggested
      that these isoforms of PLA(2) belong to class I PLA(2) family. PLA(2)-8 was
      highly homologous (81%) to Notechis scutatus scutatus (Australian tiger snake)
      PLA(2), PLA(2)-9 and PLA(2)-384 showed fairly high sequence homology (90%) to
      Enhydrina schistosa (beaked sea snake) PLA(2), indicating that they might have
      similar functions. These results reflect the diversity of Lapemis hardwickii Gray
      PLA(2) genes. The successful cloning of these isoenzyme genes of sea snake PLA(2)
      may provide new information for the study on structure-function relationship of
      PLA(2) family and its possible molecular mechanism.

PMID- 12050800
TI  - Amplification and Cloning by Long RT-PCR of Full-length Genome of Larger Segment
      of Chicken Infectious Bursal Disease Virus.
AB  - To develop the genetic rescue techniques for infectious bursal disease virus
      (IBDV), Birnaviridae family, the full-length cDNA of the larger segment of the
      chicken IBDV was amplified and cloned by long RT-PCR. A comparison of four
      purification and extraction methods of RNA from IBDV infected chicken embryoid
      fibroblasts (CEF) showed that the ultracentrifugation followed by proteinase
      Kdigestion extracted dsRNA more effectively. Then reverse transcription was
      carried out at 50 degrees using Superscipt II enzyme, followed by RNase H
      digestion. Amplification of single stranded cDNA in a single step resulted in the
      synthesis of the full-length segment A of 3 259 bp. The amplified product was
      cloned and sequenced, identifying that it was an IBDV. This method is superior to
      other methods based on amplifying different parts of the genome many times,
      therefore the cloning procedure was simplified.

PMID- 12050801
TI  - A Candidate Oral Vaccine to Helicobacter pylori Fusion Protein of HspA and CtxB.
AB  - Heat-shock protein A subunit(HspA), an effective immunogen may stimulate the
      immunoresponse in human body against challenge of H.pylori. The B subunit of
      cholera toxin (CtxB) has been proved to be a potent mucosal immunogen, actas an
      adjuvant for vaccine targeted for delivery to the mucosal-associated lymphoid
      tissue. A recombinant plasmid expressing bivalent antigen of HspA and CtxB
      subunit was constructed as follows. hspA and ctxB gene was amplified by PCR. The
      DNA products of hspA and ctxB were inserted in the prokaryotic expression vector
      pET-22b( ), respectively, and then the resulted recombinant plasmid expressinga
      fusion protein named HCT was transformed into the E.coli strain BL-21(DE3). hct
      gene was measured to be 708 base pairs long, and the fusion protein encoding a
      polypeptide of 236 amino acid residues, corresponded to a calculated molecular
      masses of 30 kD. Western blot analysis of the recombinant protein HCT confirmed
      that it could be specifically recognized by the serum of H.pylori-infected
      patients. HspA and HCT labelled (125)I were orally administered into the stomach
      of mice, respectively, and the radioactivity of (125)I in serum of each mouse was
      assayed at intervals 15 min, 30 min, 60 min, 90 min and 120 min. The result
      indicated that there were high radioactivity counts in the groups of HCT than
      that of HspA(P 0.001). This result suggests that the CtxB may enhance the volume
      of HspA absorbed from the intestine of mice, therefore the recombinant fusion
      protein HCT may be an effective oral vaccine for prevention and treatment against
      the infection of H.pylori.

PMID- 12050802
TI  - Cloning and Expression Analysis of a Novel Gene, UBAP1, Possibly Involved in
      Ubiquitin Pathway.
AB  - The 9p21-22 region shows loss of heterozygosity in up to 60% of human
      nasopharyngeal carcinomas (NPC), indicating the presence of a tumor suppressor
      gene in this region. We have identified a novel minimal common deletion region at
      9p21-22. Twenty-two epithelial-derived expressed sequence tags (ESTs) in this
      critical region were systematically screened by differential RT-PCR to
      investigate the expression patterns in NPC cell line HNE1 and primary cultures of
      normal nasopharyngeal epithelial cells. One of these ESTs was found down
      expressed in HNE1, whose differential expression was confirmed by Northern blot.
      Subsequently the corresponding gene sequence for this EST was established by cDNA
      cloning and RACE procedures (GenBank Accession No.AF222043). Furthermore, a mouse
      homologueof this gene was identified (GenBank Accession No.AF275549). This gene
      is 2.7 kb long and contains two UBA domains. It is a new member of UBA domain
      protein family, encoding a putative protein of 502 amino acids with a theoretical
      molecular mass of 55 kD, so we have named this gene UBAP1 for ubiquitin
      associated protein 1 (HUGO Gene Nomenclature Committee-approved symbol). Northern
      blot and RT-PCR analysis demonstrated a ubiquitous pattern of gene expression in
      human and mouse tissues. Direct sequencing analysis of the coding region of
      hUBAP1 following RT-PCR failed to reveal any mutations in a preliminary screening
      of NPC cell line HNE1 and primary nasopharyngeal carcinomas samples. However,
      more detailed analysis is to be performed to reveal if fine mutations of this
      gene are present in NPC.

PMID- 12050803
TI  - Identification by Site-directed Mutagenesis of Amino Acid Residues Flanking RGD
      Motifs of Snake Venom Disintegrins for Their Structure and Function.
AB  - In order to demonstrate that the amino acid residues flanking the RGD sequence
      were important for inhibiting the ADP-induced platelet aggregation, we analyzed
      the role of the amino acid residues in the domain preceding the RGD loop on the
      activity of disintegrins. Our approach was to develop hybrids between the
      disintegrins kistrin and elegantin targeting residues in this domain and within
      the RGD loop. The basic sequence within elegantin KKKR( 44 ) T ( 45 ) I ( 46 ) /A
      (50)RGDN(54)P(55) was changed by mutagensis to SKAG ( 44 ) T ( 45 ) I ( 46
      )/P(50)RGDM(54)P(55) and to SKAG(44)I(46)/P(50)RGDM(54)P(55), thereby resembling
      the corresponding S(39)RAGT(43)/P(50)RGDM(52)P(53) sequence in kistrin. This
      changed KKKR(44)T(45)I(46)/A(50)RGDN(54)P(55)right curved arrow
      SKAG(44)T(45)I(46)/P(50)RGDM(54)P(55) dramatically reduced the activity of
      elegantin as an inhibitor of platelet aggregation. In contrast, deletion of T(45)
      (KKKR(44)T(45)I(46)/A(50)RGDN(54)P(55)right curved arrow
      SKAG(44)T(45)I(46)/P(50)RGDM(54)P(55))increased activity of elegantin as an
      inhibitor platelet aggregation. It was further shown that their electrophoresis
      properties were very different. These data highlight the importance of the domain
      encompassing residues 39--45 and the amimo acid residues flanking the RGD
      sequence on disintegrin structure-function.

PMID- 12050804
TI  - Identification and Structural Analysis of a Class of Potentially Transposable
      Solo-LTR in Rice Genome.
AB  - Two solo-LTRs, named SLTR1 and SLTR2, were found in BAC t17804 and q5343 on rice
      chromosome 4, respectively. SLTR1 is in a 18 S rRNA gene and SLTR2 is in a
      retrotransposon. They share sequence homology and show sequence similarity 89.1%
      and 70.1% to the LTR of rice retrotransposon RIRE8, respectively. SLTR1 and SLTR2
      are of gypsy retrotransposons of rice. They are both highly repetitive sequences
      and widely distributed in the rice genome, as shown by hybridization with
      specific probes of SLTR1 and SLTR2. Using PCR amplication with primers on
      flanking sequences of SLTR1 and SLTR2, no bands corresponding to those of BACs
      were amplified using the rice genomic DNA as template. SLTR1 and SLTR2 did not
      locate in the relative loci of the rice genome, as supported by hybridization
      with specific probes of genes interrupted by them. Obviously, SLTR1 and SLTR2
      reported here came from different loci of the genome by the transposition. These
      solo-LTRs may be useful for our rice genome studies.

PMID- 12050805
TI  - Structural Analysis of a Gene Cluster Encoding Two Cationic and Three Anionic
      Peroxidases from Rice Chromosome 4.
AB  - Sequence analysis of a rice BAC q3037(H0207F01) identified a cluster of five
      tandemly arranged peroxidase genes, osp1,osp2,osp3,osp4 and osp5, within a 22.5
      kb region. osp4,osp5 each have three exons interrupted by two introns, while
      osp1,osp2 and osp3 each have two exons interrupted by a single intron. The five
      genes were predicted products of 338, 335, 336, 343 and 346 amino acid residues,
      respectively, including putative signal peptide sequence at the amino-termini.
      And OSP1, OSP4 and OSP5 were predicted to be anionic peroxidase, OSP2 and OSP3
      are cationic. Comparative analysis and evolutionary analysis of the clustered
      genes and other peroxidase family members revealed that the gene cluster occurred
      by tandemly gene duplications(from osp5 to osp1) and that osp5,ap1 and prx7 were
      potential orthologies, and osp1-5, ap1 and prx7 constituted a novel evolutionary
      branch of class III peroxidases.

PMID- 12050806
TI  - Cloning and Characterization of fup1, A Gene Highly Expressed in Hepatocellular
      Carcinoma.
AB  - Primary hepatocellular carcinoma(HCC) is one of the common malignant tumors in
      China. In our previous work, a gene named fup1(function-unknown protein 1) was
      isolated that was expressed differently in HCC and in normal liver. We assumed
      that it might be a candidate oncogene for the HCC. The fup1 gene had a ORF of 1
      233 bp, encoding a protein with M(r) of 46 kD and isoelectric point of 5.48. The
      sequence characteristics showed its possible localization in nuclei. Northern
      blots showed that this gene was weakly expressed in many types of human tissues,
      except in the heart, implying its tissue-specific expression pattern. MTT assay
      of the NIH 3T3 cells transfected with this gene in the form of recombinant
      eukaryotic expression plasmid showed its enhancing role to cellular
      proliferation.

PMID- 12050807
TI  - Genome Structure and the p10 Gene of the Helicoverpa armigera
      Nucleopolyhedrovirus.
AB  - The genomic DNA of Helicoverpa armigera single-nucleocapsid nucleopolyhedrovirus
      (C1 clone) was digested with BamHI, EcoRV, HindIII, KpnI, PstI and XbaI,
      respectively, and formed 11, 31, 13, 6, 7, and 25 fragments larger than 400 bp,
      respectively. The size of genome was estimated to be about 130.7 kb. A detailed
      physical map was constructed for the six restriction enzymes. The five homologous
      region, hr1, hr2, hr3, hr4 and hr5, and the ten genes including polyhedrin gene
      (ph), immediate-early gene(ie1), p74, p10, chitinase gene, DNA directed DNA
      polymerase gene (DNApol), helicase gene, superoxide dismutase gene (sod),
      alkaline-exonuclease gene (alk-exo), ecdysteroid UDP-glucosyltransferase gene
      (egt) were identified and their locations in the genome were determined. The
      genome organization of HaSNPV is quite different from those of other NPVs ever
      determined. The p10 gene was located in the fragment BamHI-I(1.89 kb) with the
      transcriptional direction opposite to the polyhedrin gene. Upstream and
      downstream of the p10 gene were p26 and p74 gene, respectively. The
      transcriptional direction of p26 is the same as that of p10 gene, and opposite to
      that of the p74 gene. The ORF encoding p10 was 261 nucleotide long and encoding a
      putative 87 amino acid polypeptide of 9.3 kD. The immediate upsteam region of the
      p10 was an A-rich region, and aconserved TAAG motif, associated with
      transcriptional start sites in other p10 genes, was identified at a site 52
      nucleotides upstream of the start codon ATG. A putative polyadenylation signal,
      AATAAA, was found 20 nucleotides downstream of the termination codon.

PMID- 12050808
TI  - Glutathione S-transferase pi Protects Serum Depletion-induced Cell Death by
      Inhibiting ASK1-MKK7-JNK Pathway in the 293 Cells.
AB  - Glutathione S-transferase pi (GSTpi) protects cells from death by altering
      intracellular oxidative stress. In order to understand the mechanism of GSTpi
      protection, a cell death model induced by serum depletion as the stress was
      established. Cotransfection of apoptosis signal-regulating kinase 1 (ASK1) and
      GSTpi cDNA was performed to elucidate the impact of GSTpi on ASK1 activity, as
      well as on its downstream signals, MKK7 and JNK, and to elucidate the potential
      protection of GSTpi on 293 cell death induced by serum depletion. The dominant
      negative mutant of JNK was used to explore if the blocking of the JNK pathway led
      to cell death inhibition. It was found that GSTpi had a dose-dependent inhibitory
      effect on activation induced by serum depletion, and also on inhibition both on
      MKK7 and JNK. Intracellular expression of GSTpi significantly inhibited serum
      depletion-induced cell death. Blocking the JNK pathway by transfection of a
      dominant negative form of JNK (JNK (APF)) brought about significant inhibition of
      cell death induced by serum depletion with an inhibiting rate as high as 15%. All
      the results suggest that the mechanism of GSTpi protection on serum depletion
      induced cell death works through an ASK1-MKK7-JNK pathway.

PMID- 12050809
TI  - Identification of Up-regulated Genes in Rat Regenerating Liver Tissue by
      Suppression Subtractive Hybridization.
AB  - Suppression subtractive hybridization (SSH) technique was used to screen up
      regulated genes in regenerating liver. The cDNA from rat regenerating liver
      tissue was used as the tester, and that from normal liver was used as the driver.
      After cloning, a subtraction cDNA library of 900 clones was obtained. These 900
      clones were further analyzed by differential gene expression screening, and 50
      clones with obvious overexpression in regenerating liver were identified.
      Sequencing analysis and homology searching showed that these clones represent 37
      genes, 13 of them are homologous to genes known to be involved in liver
      regeneration 15 are known genes which are first found to be up-regulated in
      regenerating liver and 9 are novel genes (ESTs) which have been deposited to
      GenBank. RNA dot blotting analysis was used to further study the gene expression
      patterns. The results not only confirmed the up-regulation of these genes in
      regenerating liver tissue, but also showed that these genes had different
      expression patterns during the process of liver regeneration. The results implied
      that these genes might play important roles in liver regeneration.

PMID- 12050810
TI  - Construction of Candida albicans Two-hybrid Library and Screening for Proteins
      Interacting with Crk1.
AB  - In order to study interactions among proteins involved in Candida albicans
      morphorgenesis, C.albicans genomic DNA was digested with Sau3AI and fused to
      activating domain(AD) of LEXA to construct an AD-fused C.albicans genomic DNA
      expression library. The library contained 7.7x10(4) independent clones and
      included 1.2x10(5) kb DNA which was 10 fold of the C.albicans whole genomic DNA.
      The CRK1 gene encodes a CDC2-related protein, that was involved in morphorgenesis
      of C.albicans. The Crk1 fused to DNA binding domain of LexA was used as the bait
      to screen the LexA library. Among 9x10(5) transformants, eight Leu and LacZ
      double positive clones were selected. With restriction enzyme analysis, three
      kinds of fragments were identified. The clones NJ1, NJ2, NJ3 were sequenced and
      analyzed with BLAST program. It was found that NJ1, NJ2, NJ3 were homologs of
      S.cerevisiae gene STI1, RET2 and NFI1, respectively. The kinase domain of
      Crk1(Crk1N)interacted weakly with protein encoded by NJ1, while the noncatalytic
      domain of Crk1(Crk1C) interacted strongly with proteins encoded by NJ2 and NJ3.
      The interaction of NJ3 and Crk1C was verified by the coimmunoprecipition of NJ3
      HA with Crk1C-LexA. These proteins may be involved in maturation, transport,
      localization, and activity regulation of the Crk1.

PMID- 12050811
TI  - Cloning and Expression of Luffin-b cDNA from the Seeds of Luffa cylindrica.
AB  - Luffin-b with Mr. 28 kD, isolated from the seeds of Luffa cylindrica,is one of
      the most toxic single chain plant ribosome inactivating proteins. The cDNA
      sequence of luffin-b was already reported by Kataoka in 1992. In this work, the
      luffin-b gene(lufB) coding sequence was cloned from the fresh seeds of Luffa
      cylindrica by RT-PCR, and the coding sequence of the gene was shown to be
      identical with that determined by Kataoka. The lufB expression plasmid was
      constructed by inserting the lufB cDNA fragment into vector pET24a( ), and the
      pET24a( )- lufB vector was expressed in E.coli by 0.5 mmol/L IPTG induction. The
      recombinant product, which mainly existed in inclusion bodies, was identified by
      SDS-PAGE and Western blotting. The recombinant luffin-b, which was renatured by
      dialysis with step by step decreasing concentration of urea, showed high activity
      of ribosome inactivation.

PMID- 12050812
TI  - Cloning, Expression, Purification and Activity of the hsBLyS.
AB  - The full length cDNA of human B lymphocyte stimulator (hBLyS) was amplified by
      using PCR method from cDNA library of human placenta. After purifying and
      sequencing, the DNA fragment of functional domain of hBLyS (hsDNA fragment)was
      amplified by using nested PCR method from the PCR product. The prokaryotic
      expression plasmid pET-30a( )/ hBLyS was constructed with recombinant DNA
      techniques after purifying and identifying the hsDNA fragment. Then the plasmid
      pET-30a( )/ hBLyS was transformed into lambdaDE3 cells and the recombination
      protein was found to be highly expressed the expression product was purified by
      affinity chromatography gel, Ni(2 )-IDA, made in our laboratory. The experimental
      results showed that the sequence of the PCR product was identical with the
      published hBLyS cDNA sequence and purity of the recombination protein we obtained
      was high. The activity of the purified recombination protein was very significant
      in the proliferation test of B lymphocytes.

PMID- 12050813
TI  - Effects of the Loach Polysaccharide on Removal of Reactive Oxygen Species and
      Protection of DNA Chains.
AB  - The effects of the Misgurnus anguillicaudatus polysaccharide on removal of
      reactive oxygen species in some modified chemical systems were investigated by
      chemiluminescence and spectrophotometry. The inhibition of the damage of DNA
      chain induced by hydroxyl radical by the Misgurnus anguillicaudatus
      polysaccharide was observed by chemiluminescence. The results showed that the
      Misgurnus anguillicaudatus polysaccharide could efficiently remove O.(-)(2),.OH,
      H(2)O(2) and other active compounds of oxygen and significantly protected DNA
      chains from being damaged by free radicals.

PMID- 12050814
TI  - PCR-aided Synthesis and Stable Expression in E.coli of the cryIA (c)Bt Gene.
AB  - Insecticidal crystal proteins, known as delta-endotoxins, from a gram-positive
      bacterium Bacillus thuringiensis have been used as bio-pesticides for over 3
      decades. By using a successive PCR method, the 1.8 kb cryIA (c)Bt gene coding for
      the fragment of protoxin was synthesized. Different from B. thuringiensis subsp.
      kurstaki Hd 73 cry gene, the synthesized gene has the codon usage pattern of an
      average Pseudomonas spp gene. 614 nucleotides were changed in the synthesized
      cryIA (c)Bt gene and the G C content was increased from 37.2% to 64%. The
      synthesized cryIA (c)Bt gene was cloned into pUT56 vector under the tac promoter
      and T1-T2 terminator. SDS-PAGE analysis revealed that 66 kD protein of the
      modified cryIA (c)Bt gene was expressed in E.coli and accounted for about 30% of
      total protein in the bacterial cells. Bioassays using crude expression products
      from host strains indicated that they had high toxicity to third instar larvae of
      the cabbage butterfly (Pieris brassicae). The LD(50) was calculated to be 0.024
      &mgr;g/cm(2).

PMID- 12050815
TI  - Expression, Purification and in vitro Activity of Apoptin.
AB  - A novel protein named apoptin induces a p53-independent, Bcl-2 insensitive type
      apoptosis in various human tumor cells but not in normal cells. Apoptin is
      considered to be a promising candidate for safe and effective anti-tumortherapy.
      Moreover, apoptin may be important for fundamental studies on molecularbasis of
      apoptosis and cancer. Apoptin gene was subcloned into prokaryotic expression
      vector pPROEXHT and pBV220, respectively. The apoptin protein was obtained from
      pPROEXHT-apoptin expression system and not from pBV220-apoptin the former
      contains a 6xhistidine affinity tag for ease of purification. Expressed protein
      was purified by chromatography on a co-chelated affinity column and was renatured
      by dialysis. The renatured apoptin was able to induce purified Hela nuclei
      apoptosis in vitro even without the participation of the cytoplasm, showing that
      apoptin expressed in E.coli was active to induce apoptosis.

PMID- 12050816
TI  - Small Subunit Ribosomal RNA Genes of Microsporidia.
AB  - Microsporidia are ubiquitous intracellular parasitic protozoa infecting all types
      of animals. Their ribosomes and rRNAs are of prokaryotic size.In order to better
      understand their phylogenetic relationship and identify the uncertain species,
      the sequences of the small subunit ribosomal RNA (ssurRNA, 16 S rRNA) genes of
      nine microsporidia infectious to the silkworm, Bombyx mori, were determined. The
      results of phylogenetic trees and Southern blotting suggest all the nine strains
      of microsporidia are various species of the genus Nosema.

PMID- 12050817
TI  - Treatment of Tumor in Mice by Oral Administration of Cytosine Deaminase Gene
      Carried in Live Attenuated Salmonella.
AB  - To study the possibility of oral gene therapy using live attenuated Salmonella,
      eukaryotic expression vectors EGFPN1, pLCDSN were introduced into a live
      attenuated AraA(-) auxotrophic mutant of Salmonella typhimurium (SL3261) and were
      administered orally to BALB/c and C57BL/6 mice. After six weeks, these mice were
      challenged with 4T(1) and Lewis cancer cells. Until the tumors reached to about
      10 mm in diameter, 5-fluorocytosine was given through intraperitoneal injection.
      Flow cytometry, confocal microscopy and PCR methods were used to detect the
      integration and expression of the genes. The inhibition of the tumor and the
      survival time of the mice were also investigated. Results showed that cytosine
      deaminase gene integration could be detected in almost all kinds of mice tissue.
      And the GFP expression was much stronger in spleen and tumor than in other
      tissues. Cytosine deaminase/5-fluorocytosine system had significant
      antitumoractivities in vivo. The anti-tumor activities of cytosine deaminase/5
      fluorocytosine at 500 mg/kg on 4T(1) and Lewis carcinoma in BALB/c and C57BL/6
      mice were more potent than the efficiency of 5-fluorouracil 10 mg/kg(P 0.05).
      Therefor, this experiment demonstrates the potential value of live attenuated
      Salmonella as carrier for oral gene therapy.

PMID- 12050818
TI  - Coexpression of DNA Fragmentation Factor Subunits in E.coli by Two Incompatible
      Plasmids.
AB  - The human DNA fragmentation factor (DFF) is a heterodimer of 40 kD (DFF40/CAD)
      and 45 kD(DFF45/ICAD) subunits. Apoptotic DNA fragmentation and chromatin
      condensation are mediated by the caspase-activated DFF40 nuclease, which is
      inhibited by a chaperone-like subunit DFF45. In this work, the coding regions of
      human DFF45 and DFF40 mRNAs were amplified from total RNA of HeLa cells by RT
      PCR. Two 1 kb DNA fragments were obtained and were cloned into a kanamycin
      resistant bacterial expression vector, pET-28a( ), generating pET28a-DFF45 and
      pET28a-DFF40, which were then used to transform E.coli BL21(DE3), respectively.
      After induction with IPTG, DFF45 and DFF40 were expressed effectively, accounting
      for about 56% and 22% of total bacterial proteins, respectively. Since successful
      expression of properly folded DFF40 requires coexpression with DFF45, the full
      length DFF45 cDNA was inserted into an ampicillin resistant expression vector,
      pET-21a( ), and the recombinant plasmid was designated pET21a-DFF45. Under
      screening pressure by ampicillin and kanamycin simultaneously, E.coli BL21(DE3)
      was cotransformed with pET21a-DFF45 and pET28a-DFF40. Upon induction with IPTG,
      DFF45 and DFF40 were coexpressed efficiently and the desired products comprised
      about 30% and 17% of total cell proteins, respectively. To further study the
      stability of the two incompatible plasmids'coexistance in E.coli, the
      cotransformant was cultured in liquid medium containing ampicillin and kanamycin
      for 14 h, and more than 75% of the cells were found to be resistant to the two
      antibiotics, that is, they carried both pET21a-DFF45 and pET28a-DFF40. Thus, a
      novel method of coexpressing different proteins using two incompatible plasmids
      was developed.

PMID- 12050819
TI  - Expression of Human Single Chain Interleukin 12 Gene in Drosophila Cells.
AB  - The hscIL-12 gene(no signal sequence), amplified by PCR, was subcloned into an
      expressing vector pMT/Bip/V5. The recombinant plasmid was transferedinto
      Drosophila cell line S2. The secreted hscIL-12 fusion protein was identified by
      Western blot, and the bioactivity of hscIL-12 was investigated by lymphocyte
      proliferation assay. The results showed hscIL-12 expressed in S2 cells could
      stimulate lymphocyte proliferation in dose-dependent manner. hscIL-12 has
      bioactivity identical to natural interleukin 12. These findings suggest that
      hscIL-12 is promising in theoretical reseach and in clinical use.

PMID- 12050820
TI  - Screening of Genes Related to the Expression of Human epsilon-globin Gene by
      Using Yeast One-hybrid System.
AB  - The developmental stage-specific silencing of the human epsilon-globin gene
      during embryonic period is controlled, in part, by a silencer (from -392 to -177
      bp) upstream of this gene. In our previous work, by using DNase I footprinting
      assay, a major protected region from -278 to -235 bp within this silencer DNA was
      identified. In order to isolate genes encoding proteins that bind to this target
      element, a human fetal liver cDNA library was screened by using yeast one-hybrid
      system. The candidate clones were sequenced, and the ribosomal protein L3 (RPL3)
      was preliminarily isolated. Electrophoretic mobility shift assay (EMSA) and
      competition tests also demonstrated its binding activity to the target element.
      These imply that RPL3 might play an important role in silencing the human
      embryonic epsilon-globin gene expression through the interaction with this
      silencer.

PMID- 12050821
TI  - Effects of Cyclosporine A and Highly Expressed Bcl-2 on Apoptosis of HL-60 Cells
      Induced by EGTA.
AB  - Effects of mitochondrial permeability transition pore-specific inhibitor
      cyclosporine A (CsA) and highly expressed Bcl-2 on the apoptosis of HL-60 cells
      induced by EGTA were studied. Detection of apoptotic peak by flow cytometry,
      fluorescent microscope observation of chromatin condensation with double staining
      of PI and Hoechst33342 and DNA ladder analysis all demonstrated that CsA
      obviously enhanced the apoptosis of HL-60 cells induced by EGTA, while highly
      expressed Bcl-2 completely blocked it. It is revealed by mitochondrial membrane
      potential (deltapsi(m)) fluorescent probes rhodamine 123 and CMXRos that the
      deltapsi(m) decreased in the apoptosis of HL-60 cells induced by EGTA. CsA
      enhanced the decrease of deltapsi(m), but highly expressed Bcl-2 increased
      deltapsi(m) of HL-60 cells about 2-fold and completely blocked the decrease of
      deltapsi(m).

PMID- 12050823
TI  - A global perspective on genetic variation at the ADH genes reveals unusual
      patterns of linkage disequilibrium and diversity.
AB  - Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown
      to be associated with an effect that is protective against alcoholism. Previous
      work from our laboratory has shown that the two sites showing the association are
      in linkage disequilibrium and has identified the ADH1B Arg47His site as
      causative, with the ADH1C Ile349Val site showing association only because of the
      disequilibrium. Here, we describe an initial study of the nature of linkage
      disequilibrium and genetic variation, in population samples from different
      regions of the world, in a larger segment of the ADH cluster (including the three
      Class I ADH genes and ADH7). Linkage disequilibrium across approximately 40 kb of
      the Class I ADH cluster is moderate to strong in all population samples that we
      studied. We observed nominally significant pairwise linkage disequilibrium, in
      some populations, between the ADH7 site and some Class I ADH sites, at moderate
      values and at a molecular distance as great as 100 kb. Our data indicate (1) that
      most ADH-alcoholism association studies have failed to consider many sites in the
      ADH cluster that may harbor etiologically significant alleles and (2) that the
      relevance of the various ADH sites will be population dependent. Some individual
      sites in the Class I ADH cluster show Fst values that are among the highest seen
      among several dozen unlinked sites that were studied in the same subset of
      populations. The high Fst values can be attributed to the discrepant frequencies
      of specific alleles in eastern Asia relative to those in other regions of the
      world. These alleles are part of a single haplotype that exists at high (>65%)
      frequency only in the eastern-Asian samples. It seems unlikely that this
      haplotype, which is rare or unobserved in other populations, reached such high
      frequency because of random genetic drift alone.

PMID- 12050824
TI  - Tilmicosin reduces lipopolysaccharide-stimulated bovine alveolar macrophage
      prostaglandin E(2) production via a mechanism involving phospholipases.
AB  - Tilmicosin is a potent antimicrobial with broad-spectrum activity against the
      bacterial agents involved in the bovine respiratory disease complex. Recent
      studies indicate that in addition to being bactericidal, tilmicosin is capable of
      modulating inflammation in the lung. A series of experiments were designed to
      determine whether tilmicosin alters alveolar macrophage-prostaglandin E(2)
      (PGE(2)) production induced by Escherichia coli (O55:B5) lipopolysaccharide
      (LPS). Twenty-two healthy Holstein bull calves were used to study the effects of
      LPS-induced PGE(2) production of alveolar macrophages after in vivo or in vitro
      treatment with tilmicosin. In Experiment 1, tilmicosin was given by subcutaneous
      injection (15 mg/kg) twice, 48 hours apart, to four calves; four control calves
      received no treatment. Twenty-four hours after the second treatment, alveolar
      macrophages were stimulated with LPS in vitro. In Experiment 2, alveolar
      macrophages from five untreated calves were harvested and treated in vitro with
      tilmicosin, followed by LPS stimulation. In Experiment 3, the ability of in vitro
      tilmicosin treatment to alter the expression of LPS-induced cyclooxygenase-2 (COX
      2) mRNA was evaluated. In Experiments 4 and 5, secretory phospholipase A(2)
      activity was examined in untreated calves. Treatment of calves with tilmicosin
      resulted in reduced LPS-induced alveolar macrophage PGE(2) production. Similar
      reductions in PGE(2) by LPS-stimulated alveolar macrophages after in vitro
      tilmicosin treatment were noted. This in vitro tilmicosin treatment was not
      associated with reduction of the expression of LPS-induced COX-2. Alveolar
      macrophage phospholipase A(2) activity induced by LPS was significantly reduced
      by prior tilmicosin treatment in vitro. Tilmicosin (in vivo and in vitro) appears
      to reduce the PGE(2) eicosanoid response of LPS-stimulated alveolar macrophages
      by reducing the in vitro substrate availability without altering in vitro COX-2
      mRNA expression.

PMID- 12050826
TI  - Evaluation of pancreatic forceps biopsy by laparoscopy in healthy beagles.
AB  - The effects of laparoscopic biopsies were determined in four healthy laboratory
      beagles. Biopsies were taken from the pancreas of three dogs and from the
      peripancreatic fat of one dog. Clinical examinations and blood sampling for
      hematologic and biochemical tests were performed before laparoscopy and weekly
      throughout each dog's participation in the study (7 or 21 days). No clinical
      signs of pancreatitis were observed, and hematologic and biochemical parameters
      remained within normal limits in three dogs. One dog exhibited a transient
      increase in trypsinlike immunoreactivity, amylase, and lipase. Minor adhesions
      between the pancreas, small intestine, and peritoneum were observed
      macroscopically in this dog. Histologically, granulation tissue and a mild
      nonsuppurative inflammation in the pancreas were present. No abnormal changes
      were seen macroscopically or histologically in the other two dogs for which
      pancreatic biopsies were performed. Thus, laparoscopy appears to be safe, with
      neither permanent abnormalities in blood parameters nor changes in clinical
      health occurring during or after the procedure in healthy beagles.

PMID- 12050825
TI  - Dose determination and confirmation for ceftiofur crystalline-free acid
      administered in the posterior aspect of the ear for control and treatment of
      bovine respiratory disease.
AB  - Three studies were conducted to determine and confirm the effective dosage rate
      of ceftiofur crystalline-free acid sterile suspension (CCFA-SS, 200 mg ceftiofur
      equivalents [CE]/ml), a long-acting ceftiofur formulation, for control and
      treatment of bovine respiratory disease (BRD). In each study, CCFA-SS was
      administered once by subcutaneous (SC) injection in the middle third of the
      posterior aspect of the ear. Study 1 was conducted using an intratracheal
      challenge with Mannheimia (formerly Pasteurella) haemolytica and dosages ranging
      from 0 to 8.8 mg CE/kg to select a dosage for further field testing. In Study 2,
      a single dose of CCFA-SS at 0.0, 4.4, or 6.6 mg CE/kg was administered when
      uniform clinical signs of BRD were present in feedlot cattle. Study 3 was
      conducted in several feedlots to evaluate the efficacy, practicality, and safety
      of CCFA-SS at 4.4 or 6.6 mg CE/kg compared with a placebo control or tilmicosin
      for preemptive control of BRD. In Study 1, the effective dose was determined to
      be 5.35 mg CE/kg; therefore, 4.4 and 6.6 mg CE/kg were selected as the dosages
      for further field testing. Administration of CCFA-SS at 4.4 or 6.6 mg CE/kg
      improved treatment success compared with negative controls (P < or =.05 for both
      doses) in Study 2. In Study 3, a single administration of 4.4 or 6.6 mg CE/kg was
      comparable to tilmicosin (P <.001) and was significantly better than placebo (P
      <.001) for the control of BRD. Using the ear as an administration site was
      acceptable under field conditions and was well tolerated by all animals. These
      studies demonstrated that a single administration of CCFA-SS by SC injection in
      the middle third of the posterior aspect of the ear at 4.4 or 6.6 mg CE/kg is
      effective, safe, and practical for preemptive control and treatment of the
      bacterial component of BRD in feedlot cattle. Administration in an inedible
      tissue results in a short withdrawal time and no injection-site trimming at
      slaughter.

PMID- 12050827
TI  - Effect of flunixin meglumine on selected physiologic and performance parameters
      of athletically conditioned thoroughbred horses subjected to an incremental
      exercise stress test.
AB  - Twelve clinically sound, healthy, athletically conditioned Thoroughbred horses
      were subjected to an incremental exercise stress test to determine the effects
      and period of detection of a single dose of flunixin meglumine (1.1 mg/kg by
      intravenous injection) in serum and urine by ELISA. Flunixin concentrations,
      performance, and hematologic and clinical chemical parameters were measured. All
      horses were rotated through four treatment groups of a Latin-square design
      providing for each horse to serve as its own control. Flunixin meglumine reduced
      prostaglandin F(1alpha) and thromboxane concentrations that had been increased by
      intense exercise. Performance parameters did not improve and prostaglandin
      concentrations did not significantly correlate with total run time. Exercise did
      not change the flunixin elimination profile in either serum or urine, and
      concentrations were found to be below the detection limit of the ELISA test
      within 36 hours in serum and 120 hours in urine.

PMID- 12050829
TI  - Repellency and efficacy of 65% permethrin and selamectin spot-on formulations
      against Ixodes ricinus ticks on dogs.
AB  - Two topically applied spot-on products used for flea and tick control on dogs,
      65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health
      Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold
      [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and
      efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe.
      Eighteen dogs were evenly and randomly allocated to the following treatments: 1)
      65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical
      application of the assigned product in accordance with product label directions
      on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for
      2 hours to 50 unfed, adult ticks in a cage with a carpet that covered
      approximately 70% of the floor area. After the exposure period, dogs were removed
      from the cages and live and dead ticks were counted on the dogs and in the cages.
      The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated
      with 65% permethrin (P <.0001 versus controls and selamectin), compared with
      10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The
      repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P
      <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9%
      repellency for selamectin (P >.05 versus controls).

PMID- 12050828
TI  - Effect of sulfadiazine and pyrimethamine on selected physiologic and performance
      parameters in athletically conditioned thoroughbred horses during an incremental
      exercise stress test.
AB  - Following the regimen used to treat equine protozoal myeloencephalitis,
      sulfadiazine (20 mg/kg) and pyrimethamine (1mg/kg) were administered orally once
      daily to 12 physically conditioned Thoroughbred horses for 4 consecutive days.
      The horses were randomly assigned to two test groups in a crossover design, with
      each horse serving as its own control. A stepwise exercise stress test was
      conducted to exhaustion. No effect on athletic performance was observed, and only
      marginal effects were noted in some hematologic and serochemical measurements,
      including decreased total white blood cell counts, red blood cell distribution
      width, total hemoglobin, serum sodium, and serum chloride. Serum folic acid
      concentration decreased significantly following sulfadiazine/pyrimethamine
      treatment.

PMID- 12050830
TI  - Effect of topical ophthalmic latanoprost on intraocular pressure in normal
      horses.
AB  - The ocular effects of latanoprost ophthalmic solution were evaluated in two
      studies, with eight horses in each study. One eye of each horse was treated with
      latanoprost ophthalmic solution once daily for 5 days, and the opposite eye
      received a control solution of sterile eyewash. Intraocular pressure and
      pupillary diameter were measured daily for 5 days after treatment. Latanoprost
      had no significant effect on intraocular pressure or pupillary diameter in normal
      horse eyes compared with control eyes in these studies. Placement of an eyelid
      nerve block resulted in significantly lower intraocular pressure.

PMID- 12050832
TI  - Antihistamines in the management of canine atopic dermatitis: a retrospective
      study of 171 dogs (1992-1998).
AB  - Antihistamines were prescribed for 178 of 271 dogs with a diagnosis of atopic
      dermatitis at the Veterinary Medical Teaching Hospital of the University of
      California, Davis from 1992 to 1998. Fifty-four percent of 166 dogs given
      antihistamines responded favorably to these treatments, with 27% of the responses
      rated as good and 27% rated as moderate. Diphenhydramine and hydroxyzine were the
      most commonly used antihistamines and were the most frequently effective.
      Chlorpheniramine and clemastine were administered less frequently and had much
      lower positive response rates. Responses to antihistamines as a group were
      significantly better in dogs having onset of clinical signs at younger ages (odds
      ratios for 1-year increase in age = 0.72, 95% confidence interval = 0.57 to 0.91,
      P =.005).

PMID- 12050831
TI  - Effects of two preanesthetic regimens for ophthalmic surgery on intraocular
      pressure and cardiovascular measurements in dogs.
AB  - The effects of different preanesthetic medications (acepromazine plus either
      meperidine or butorphanol) given before the induction of anesthesia with
      midazolam and ketamine on intraocular pressure, heart rate, and arterial blood
      pressure were investigated in 20 dogs. Following administration of preanesthetics
      and induction of anesthesia, dogs were intubated and anesthesia was maintained
      with halothane for 10 minutes. Intraocular pressure was significantly higher (P
      <.05) at several evaluations for dogs premedicated with acepromazine/meperidine
      than for those premedicated with acepromazine/butorphanol. Mean heart rate and
      diastolic arterial blood pressure were significantly (P <.05) higher 5 minutes
      after administration of acepromazine/meperidine than after
      acepromazine/butorphanol. Results of this study suggest that
      acepromazine/butorphanol is a satisfactory preanesthetic combination to use
      before induction of anesthesia with midazolam and ketamine for ophthalmic surgery
      in dogs.

PMID- 12050833
TI  - Hereditary and clinical characteristics of lateral luxation of the superficial
      digital flexor tendon in Shetland sheepdogs.
AB  - A study was conducted to define the mode of inheritance of lateral luxation of
      the superficial digital flexor (SDF) tendon in different lines of Shetland
      sheepdogs by examination of pedigree data. This pedigree analysis included
      affected and unaffected dams, sires, and offspring; common clinical signs; and
      age at onset. The clinical, histopathologic, and radiographic features of the
      disease were also studied. Of the 14 offspring from five matings of an affected
      sire to unrelated affected females, 100% were affected with lateral luxation of
      the SDF tendon. Of the 59 offspring from the same affected sire to unrelated,
      unaffected females, 44% were affected. The mating between normal parents produced
      61% unaffected and 39% affected offspring. Application of the phenotypic findings
      in this study to a Mendelian genetic model of inheritance suggests that lateral
      luxation of the superficial digital tendon in Shetland sheepdogs is inherited as
      a simple autosomal recessive trait.

PMID- 12050834
TI  - An amazing experience.

PMID- 12050835
TI  - The use of ice for pain associated with chest tube removal.
AB  - Every year more than 300,000 patients undergo cardiothoracic surgery, requiring
      placement of at least one chest tube. Removal of these chest tubes has been
      described as one of the worst intensive care unit experiences for these patients.
      Pain associated with chest tube removal (CTR) has been poorly controlled in many
      surgical patients. The purpose of this experimental study was to ascertain if the
      application of ice would decrease pain before, during, and after chest tube
      removal. Fifty postcardiac surgery patients were randomly assigned to two groups.
      The experimental group received ice therapy before CTR, whereas control subjects
      received a placebo. Pain intensity and pain distress were measured on a 0-10
      numeric rating scale, and pain quality was measured using the McGill Pain
      Questionnaire-Short Form (MPQ-SF). Differences in pain intensity and pain
      distress between the experimental and control groups were not significant. A
      significant change in pain over time was noted in both groups, with pain
      intensity and distress being most severe during actual chest tube removal.
      Additionally, patients who received preprocedural pain medication did not differ
      in their levels of pain intensity or distress. Both groups used all the quality
      descriptors on the MPQ-SF for the sensory and affective components of pain, with
      cramping and gnawing as the most frequently chosen words. Continued research with
      larger samples is encouraged to further evaluate ice and other interventions that
      can be used to manage pain associated with CTR.

PMID- 12050836
TI  - Cardiovascular surgery patients' respiratory responses to morphine before
      extubation.
AB  - Analgesia is commonly withheld from cardiovascular surgery patients who are soon
      to be withdrawn from mechanical ventilation to prevent respiratory depression
      that can postpone extubation. The effects of analgesia on respiration have not
      been studied adequately. In this study, weaning parameter measurements were
      obtained to determine the respiratory impact of a low dose of intravenous
      morphine administered to cardiovascular surgery patients who were ready to be
      weaned from the ventilator. A pretest-posttest, quasi-experimental, repeated
      measures design was used. Eleven alert patients who experienced postoperative
      pain and met two of five weaning parameter criteria received 1 mg to 5 mg of
      morphine. Weaning parameters were measured before the intervention and at 15 and
      30 minutes afterward. As hypothesized, the administration of low-dose morphine
      did not have a negative effect on weaning parameters. Mean weaning parameter
      values either increased or remained the same after the administration of
      morphine. Despite the small sample size, the results of dependent t tests
      revealed statistically significant improvements, using an alpha level of 0.05, in
      the mean tidal volume and negative inspiratory force values at the 30-minute
      measurement, and in the vital capacity value at the 15-minute measurement. The
      findings from this study help to refute the notion that a low dose of intravenous
      morphine will cause respiratory depression, and further suggest that the
      administration of morphine may enhance patients' respiratory function. If
      additional research supports this study's findings, both the goals of weaning
      postoperative patients from the ventilator and controlling pain may be achieved
      simultaneously.

PMID- 12050837
TI  - Relaxation and music reduce pain after gynecologic surgery.
AB  - The purpose of this randomized controlled trial was to investigate the effect of
      three nonpharmacologic nursing interventions: relaxation, music, and the
      combination of relaxation and music on pain following gynecologic (GYN) surgery.
      A total of 311 patients, ages 18 to 70, from five Midwestern hospitals, were
      randomly assigned using minimization to either three intervention groups or a
      control group and were tested during ambulation and rest on postoperative days 1
      and 2. Pain sensation and distress were measured using visual analogue scales.
      Multivariate analysis of covariance of posttest sensation and distress was used
      with pretest control and a priori contrasts. The intervention groups had
      significantly less posttest pain than the control group (p =.022-.001) on both
      days. The three interventions were similar in their effect on pain. Patients who
      received the interventions plus patient-controlled analgesia (PCA) had 9% to 29%
      less pain than controls who used PCA alone. Reduced pain was related to amount of
      activity (ambulation or rest), mastery of the use of the intervention, and
      decreased pulse and respiration. Those who slept well had less pain the following
      day. Nurses who care for GYN surgical patients can provide soft music and
      relaxation tapes and instruct patients to use them during postoperative
      ambulation and also at rest on days 1 and 2.

PMID- 12050838
TI  - Registered nurses' choices regarding the use of intradermal lidocaine for
      intravenous insertions: the challenge of changing practice.
AB  - After a policy change that required that lidocaine be offered to every patient
      before an intravenous (IV) insertion, registered nurses (RNs) in this rural acute
      care hospital were interviewed to determine whether they had changed their
      practice. This study reports on the percentage of RNs who offered lidocaine
      before IV insertion and explores the perceived and actual barriers for those
      nurses who did not routinely offer patients this option. The study sample of 30
      represents 8% of the RN inpatient staff. Of the sample, 30.0% said that they
      always offer intradermal lidocaine and reported a decrease in patients' pain,
      fear, and anxiety as advantages. Another 23.3% of the RNs indicated they offered
      lidocaine only in specific circumstances based on patients' behavior and
      condition and the IV site to be used. The remaining 46.7% responded that they do
      not offer lidocaine. The reasons for not offering lidocaine included the
      perception that it made the procedure more difficult, an acknowledgment that it
      was not a part of their routine, or they did not think of it. Both the RNs who
      used the lidocaine and the RNs who did not use it referred to the fact that there
      was poor staff knowledge and skill about how to use intradermal lidocaine
      successfully. Recommendations are made for addressing the identified barriers.

PMID- 12050839
TI  - The vestibular complex in a prosimian primate (Galago senegalensis): morphology
      and spinovestibular connections.
AB  - The morphology of, and distribution of spinal afferents to, the vestibular
      complex of a prosimian primate (lesser bushbaby, Galago senegalensis) were
      studied using cytoarchitectural, myeloarchitectural and selective silver
      impregnation methods. The vestibular complex of Galago consists of superior
      (SVN), lateral (LVN), medial (MVN) and spinal (SpVN) nuclei, each nucleus having
      cell populations of characteristic size, shape and distribution within its
      borders. There is morphological and experimental evidence for the existence of
      subgroups f, 1, x, y and z and a hitherto undescribed subgroup located in
      dorsomedial portions of the rostral two-thirds of the MVN. Following partial or
      complete hemisections at cord levels C1-L6 brain stem sections were impregnated
      according to the method of Fink and Heimer. Preterminal debris is concentrated
      mainly in subgroups x and z, relatively sparse in adjacent SpVN and moderate to
      sparse in LVN and MVN following hemisections at upper and mid-cervical levels.
      Axonal debris is noticeably absent from the MVN after lesions below the C8 spinal
      level; this indicates that the MVN receives spinal input from cervical levels
      only. Following lesions at C8 and progressively lower spinal levels, degeneration
      was found primarily in subgroups x and z and in LVN and SpVN although in lesser
      amounts; as lesions were placed at progressively lower levels there was a
      proportionate decrease in the amount of axonal debris found in these respective
      nuclei. No degeneration was found in SVN following lesions at any spinal level.

PMID- 12050840
TI  - Ultrastructural studies on Purkinje cell maturation in the cerebellum of the frog
      tadpole during spontaneous and thyroxine-induced metamorphosis.
AB  - The maturation of Purkinje cells in the cerebella of both thyroxine (T4)-induced
      and normally metamorphosing tadpoles was studied by transmission electron
      microscopy, with particular reference to the perikaryal changes. During the
      latter part of the prometamorphic phase, many Purkinje cells showed hypertrophied
      apical cones filled with mitochondria, Golgi elements and rosettes of ribosomes.
      In early metamorphic climax, the perikaryal cytoplasm displayed stratification,
      with an inner zone of perinuclear Nissl bodies and an outer region of
      neurotubules. At the onset of metamorphic climax, there was an abrupt appearance
      of numerous somatic processes, as well as climbing fiber boutons which synapsed
      with them on some cells. However, many Purkinje cells did not display somatic
      processes. Stellate cell synapses also were seen in considerable numbers. As
      metamorphic climax progressed to completion, the somatic processes steadily grew
      scarce with a concomitant increase in climbing fiber synapses on the major
      dendrites. Glial ensheathment of the Purkinje cell soma was also rapidly
      accomplished during metamorphic climax. In addition, premetamorphic bullfrog
      tadpoles were induced to metamorphose prematurely following treatment with T4 and
      then compared to normally metamorphosing tadpoles. Following 3 weeks of T4
      treatment, large numbers of Purkinje cells displayed somatic processes. These
      processes were observed to be postsynaptic to climbing fibers and similar to
      those seen normally. Additionally, Purkinje cell hypertrophied apical cones were
      observed in treated tadpoles. These observations indicate that some aspects of
      Purkinje cell maturation during metamorphosis, especially the interaction of
      climbing fibers and somatic contacts, are T4-dependent. In both normal and
      induced metamorphosis, changes in frog Purkinje cells thus proceed at a tempo
      comparable to that of such gross morphological transformation as hindlimb growth.

PMID- 12050841
TI  - Correlations between major brain regions in Chiroptera.
AB  - Unlike small homogeneous nuclei, progression indices of large heterogeneous brain
      regions show no negative correlations and give no evidence of compensatory
      effects, presumably because the evolutionary progressions and regressions of
      multiple neighboring functions mask each other. The diencephalon and various
      parts of the telencephalon show large positive correlations, apparently
      reflecting the general increase in size of the brain, relatively to body weight,
      from presumably primitive to advanced forms. The neocortex is strongly correlated
      with the striatum, a putative precursor, and with the diencephalon, but less
      strongly correlated with the cerebellum in Chiroptera than in Primates. The
      mesencephalon is moderately correlated with the medulla oblongata and cerebellum,
      but uncorrelated with all parts of the telencephalon except the paleocortex. The
      bulbus olfactorius is correlated with the septum, schizocortex and hippocampus,
      but these correlations may be due mostly to the progression of these four
      structures in Megachiroptera and their regression in insectivorous
      Microchiroptera, and may not imply major direct functional relationships.

PMID- 12050842
TI  - Eye movements and related behavioral responses evoked by electrical stimulation
      of the brain in free-swimming sunfish, Lepomis cyanellus.
AB  - Areas of the sunfish brain from which eye movements related to rolling about the
      longitudinal and interpupillary axes were elicited by electrical stimulation in
      anesthetized animals (acute preparation) were also tested in free-swimming fish
      (chronic preparation). Stimulation in the oculomotor complex resulted primarily
      in bilateral backward rotation of the eyes (acute preparation), and backward
      looping of the whole animal (chronic preparation). Stimulation near the trochlear
      nerves and nuclei evoked mostly bilateral forward rotation of the eyes (acute
      preparation), and downward pitching of the head (chronic preparation). Testing
      the cerebellum in the molecular area adjacent to the eminentia granularis
      resulted in conjugate lateral rolling of the eyes (acute preparation), and side
      to-side tilts or wobbles (chronic preparation). Stimulation in the presumed
      vestibular area of the medulla triggered mainly conjugate lateral rolling of the
      eyes (acute preparation), and lateral rolling about the fish's long axis (chronic
      preparation). The results are discussed with respect to possible functional
      pathways involved in the mediation of behavioral responses to inputs from the
      otolith organs.

PMID- 12050843
TI  - Neuroevolutionary mechanisms of cerebral asymmetry in man.
AB  - Cerebral asymmetry in man has by and large been interpreted in terms of
      differences at the level of hemispheric organization. The inadequacy of a
      hemispheric interpretation as a biological account of asymmetry is discussed and
      a model of the neural mechanisms of cerebral asymmetry is developed. The model
      focuses on the functional organization of the inferior parietal cortex in human
      and non-human primates and accounts for the evolution and expression of cerebral
      asymmetry in man in terms of specific adaptations in select neural systems of
      ancestral primate brains.

PMID- 12050844
TI  - Locked into gambling: anticipatory regret as a motivator for playing the National
      Lottery.
AB  - Four hundred and eighty-five people were asked about their intentions to play the
      National Lottery in England a week prior to the introduction of a new midweek
      draw. We predicted that those people who played the Saturday game with a regular
      set of numbers would be more inclined to play the new midweek game than those who
      had not established a routine of using the same set of numbers. We further
      predicted that their motivation to play would derive from a feeling of
      'anticipatory regret'--a sense that they would find it intolerable to discover
      their regular numbers had been drawn when they hadn't purchased a ticket. Results
      supported both of these predictions, and an interpretation of the data is given
      in terms of the circumstances most likely to trigger such counterfactual
      reasoning.

PMID- 12050845
TI  - Prevention of problem gambling: modifying misconceptions and increasing
      knowledge.
AB  - Research on gambling clearly demonstrates that today's youth are very much
      involved in gambling activities. As they take part in these activities, young
      people develop and entertain irrational thoughts about gambling and become at
      risk for developing severe gambling problems. In this study, a video specifically
      designed to correct misconceptions and increase knowledge about gambling was
      tested on 424 grade 7 and 8 students. The effectiveness of the video was
      evaluated using four different experimental conditions. Findings indicated that
      the video significantly improved subjects' knowledge about gambling and corrected
      their misconceptions. The implications of these results for the prevention of
      gambling problems are discussed.

PMID- 12050846
TI  - Rapid onset of pathological gambling in machine gamblers.
AB  - A particularly rapid onset of pathological gambling (PG-onset) through the use of
      gambling machines has been widely alluded to, but this is the first study to
      empirically examine the phenomenon. This study compared the latency of PG-onset
      in those who gambled primarily on machines, compared to those who gambled
      primarily on more "traditional" forms of gambling at PG-onset. Subjects were 44
      adult pathological gamblers (PGs) seeking outpatient treatment in Rhode Island
      (17 females; mean age = 46.9). Subjects completed questionnaires and a diagnostic
      interview including a complete history of gambling activities and the course of
      PG. The "latency" of PG-onset was defined as the time (in years) elapsed between
      the age of regular involvement in the primary form of gambling and the age at
      which DSM-IV criteria were first met. "Machine" PGs (n = 25) had a significantly
      shorter latency of onset than did "traditional" PGs (1.08 years vs. 3.58 years).
      Females and machine PGs had a significantly older age of onset, but gender was
      not associated with latency of PG-onset. Lifetime comorbidity of either substance
      use disorders (SUDS) or depressive disorders (DDS) was also not associated with
      the latency of PG-onset. The results of the current study suggest that
      intrapersonal variables such as gender and comorbid disorders do not generally
      affect the speed with which people develop PG. Rather, the social, environmental,
      and stimulus features of mechanized gambling are implicated. Prospective
      longitudinal studies on the onset and course of PG are needed, as well as more
      basic research on the features of machine gambling that may contribute to rapid
      onset.

PMID- 12050847
TI  - Passion and gambling: on the validation of the Gambling Passion Scale (GPS).
AB  - Vallerand and his colleagues (Vallerand & Blanchard, 1999; Vallerand, Blanchard,
      Koestner, & Gagne, 2001) have recently proposed a new concept of passion.
      According to these authors, passion refers to a strong inclination toward an
      activity that we like, find important, and in which we invest time. Vallerand et
      al. have identified two types of passion: obsessive and harmonious. Obsessive
      passion refers to an internal pressure that forces an individual to engage in the
      activity. Harmonious passion, on the other hand, refers to an internal force that
      leads an individual to choose freely to engage in an activity. While obsessive
      passion has been shown in some circumstances to lead to negative psychological
      and physical consequences, harmonious passion generally leads to positive
      psychological and physical consequences. The purpose of the present research was
      to validate a measure of passion toward gambling: the Gambling Passion Scale
      (GPS). The GPS consists of two subscales (obsessive passion and harmonious
      passion) comprising five items each. Results from two studies involving a total
      of 340 participants revealed satisfactory internal consistency and temporal
      stability indices, as well as a two-factor structure supported by exploratory and
      confirmatory  factor analyses. Finally, a series of partial correlational
      anaylses between the two subscales and scales assessing behavioral measures
      related to gambling supported the construct validity of the GPS. The present
      results suggest that the GPS is  a useful scale for research on gambling.

PMID- 12050848
TI  - An assessment of the validity and reliability of the SOGS-RA.
AB  - The present is a validation study seeking to determine the degree of confidence
      that can be placed on inferences about problem gambling among adolescents in the
      Atlantic provinces, based on their South Oaks Gambling Screen-Revised for
      Adolescents (SOGS-RA) scores. The major source of data was a 1998 survey of
      13,549 students in junior and high school of the public school systems of the 4
      Atlantic provinces of Canada. The SOGS-RA was found to have adequate stability
      and internal consistency reliability. Statistically significant gender
      differences were demonstrated relative to endorsement and construct validity.
      Regarding the latter, this study shows that the existing cut-point of the SOGS-RA
      score for problem gambling identifies as problem gamblers, markedly different
      proportions of male than female daily gamblers. Regarding construct validity in
      relation to the Atlantic Alcohol and Drug Risk Continua, this study suggests that
      while statistically highly significant, the association between problem gambling
      and substance-related problems may be of low clinical significance. Regarding
      criterion validity, there is an urgent need to perform the types of enquiry that
      will allow clarification about how adolescent problem gambling is conceptualized,
      by adults versus adolescents, by males versus females, and from a clinical versus
      a public or population health perspective.

PMID- 12050849
TI  - Physician office-lab links. Latest and greatest or a flash of the past?

PMID- 12050850
TI  - Brainy solutions. Replacing intelligence with intelligence in automated systems.

PMID- 12050851
TI  - [A recent trend in methamphetamine-induced neurotoxicity].
AB  - The neurotoxic damage caused by methamphetamine (METH) is characterized by nerve
      terminal destruction and/or degeneration of the dopaminergic and serotonergic
      systems in striatum and hippocampus. It has been hypothesized that intraneural
      dopamine (DA) redistribution from synaptic vesicles to cytoplasmic compartments
      produced by METH is an important factor for its neurotoxicity. The METH-induced
      redistribution of DA is thought to occur after an increased production of DA
      based reactive oxygen species (ROS) (e.g., oxygen radicals and hydroxyl radicals)
      by auto-oxidation or enzymatic degradation, and METH-induced ROS produces an
      oxidative stress and depletion of energy stores. Furthermore, the glutamatergic
      system and nitric oxide (NO) may also contribute to METH-induced neurotoxicity.
      Recently, studies using several knockout strains of mice lacking the DA
      transporter, the monoamine vesicle transporter-2, c-fos, or neuronal NO synthase
      confirm a possible role of these factors in METH-induced neurotoxicity. Moreover,
      it has been proposed that METH causes the apoptosis and activation of cell-death
      related genes. For example, METH-induced neurotoxicity is reduced in bcl-2-over
      expressing neural cell and p53 knockout mice and also induces the activation of
      caspase 3. Therefore in this review, we discuss the relationship between ROS
      formation, oxidative stress, and apoptosis in METH-induced neurotoxicity.

PMID- 12050852
TI  - [Amyloid cascade hypothesis of Alzheimer's disease and alpha 7 nicotinic
      receptor].
AB  - It is known that beta amyloid protein (A beta) plays an important role in the
      pathology of Alzheimer's disease (AD). In this review, the role of cellular
      signaling in the protective action of nicotine for A beta-induced neurotoxicity
      is described. Recent biochemical and functional studies have demonstrated that A
      beta interacts directly with the alpha 7 nicotinic receptor, suggesting that A
      beta might have a function as an endogenous ligand for this receptor. Thus the
      role of alpha 7 nicotinic receptor in the A beta cascade hypothesis of AD and the
      possibility of alpha 7 nicotine receptor agonists as the therapeutic drugs for AD
      are discussed.

PMID- 12050853
TI  - [The effect on other individual presentations of the goldfish by FG7142
      injection].
AB  - To research the emotional effects on goldfish shoaling behavior, the change in
      time spent by the stimulus shoal sizes (0, 1, 2, and 5) was investigated.
      Consequently, as for shoaling behavior, a difference was seen only in the
      presence of a shoal, independent of size. The experimental goldfish were then
      injected with beta-carboline (FG7142, N-Methyl-beta-carboline-3-carboxyamide at
      0.1, 1, 2, or 4 mg/kg) or the vehicle and exposed to the stimulus fish (1). In
      the beta-carboline group with the 1 and 2 mg/kg dose, the time spent within 10 cm
      of the stimulus fish increased compared with the vehicle, and this increase was
      maintained throughout the trial. In contrast, the time spent was unchanged in the
      high-dose group (4 mg/kg). The subject fish motility was unchanged in all dose
      groups. These results are discussed in their relationship to predator avoidance.

PMID- 12050855
TI  - New kids on the block: emerging PNA-based DNA diagnostics.

PMID- 12050854
TI  - [Mechanisms of interaction between adenosine receptor subtypes on hippocampal
      serotonin release].
AB  - To clarify the mechanisms of interaction between adenosine receptor subtypes (A1R
      and A2R) on 5-HT release, the present study determined the effects of adenosine
      receptor subtypes on voltage-sensitive Ca(2+)-channels (VSCCs), protein-kinases
      (PKs) and synaptic-proteins (SNAREs) related 5-HT release using microdialysis in
      freely moving rat. A1R-antagonists increased basal 5-HT release, which was
      reduced by inhibitors of N-VSCC, PKC and syntaxin predominantly, and by
      inhibitors of PKA and synaptobrevin weakly, but was not affected by P-VSCC
      inhibitor. In the presence of A1R-antagonist, A2R-agonists increased basal 5-HT
      release, whose action was inhibited by P-VSCC, PKA and synaptobrevin inhibitors
      predominantly and reduced by N-VSCC, PKC and syntaxin inhibitors weakly. Under
      the condition of adenylate-cyclase activation in the absence of A1R-antagonists,
      A2R-agonists increased basal 5-HT release. K(+)-evoked 5-HT release was enhanced
      by A1R-antagonist and A2R-agonist, whose actions were inhibited by P-VSCC, PKA
      and synaptobrevin inhibitors predominantly. These results suggest that an
      activation of A1R suppresses 5-HT release via an inhibition of N
      VSCC/PKC/syntaxin and P-VSCC/PKA/synaptobrevin, and an activation of A2-R
      stimulates 5-HT release via an enhancement of P-VSCC/PKA/synaptobrevin. Therefore
      PKA activity plays an important role in the interaction between A1R and A2R on
      hippocampal 5-HT release.

PMID- 12050856
TI  - Roche HIV-1 PCR-based blood screening assay cleared for marketing in Italy.

PMID- 12050857
TI  - Genaissance pharmaceuticals discovers genetic markers.

PMID- 12050858
TI  - DAKO and Bayer to distribute oncology serum assays.

PMID- 12050859
TI  - Differential display in the time of microarrays.
AB  - A brief overview of major methods used for genome-wide expression profiling is
      presented. Special attention is devoted to ordered differential display,
      subtractive hybridization and DNA microarrays. Future prospects of comparative
      gene expression studies using combinations of differential display methods and
      microarray technology are outlined.

PMID- 12050860
TI  - FISH banding methods: applications in research and diagnostics.
AB  - Recently, several chromosome banding techniques based on fluorescence in situ
      hybridization (FISH) have been developed for the human and the mouse genome. In
      contrast to the standard chromosome banding techniques presently used, giving a
      protein-related banding pattern, those FISH techniques are DNA-specific.
      Currently the FISH banding methods are still under development and no high
      resolution banding technique is available that can be used for a whole genome in
      one hybridization. Nevertheless, FISH banding methods were used successfully for
      research in evolution- and radiation-biology, as well as for studies on the
      nuclear architecture. Moreover, their suitability for diagnostic purposes has
      been proven in prenatal, postnatal and tumor cytogenetics, indicating that they
      are an important tool with the potential to partly replace the conventional
      banding techniques in future.

PMID- 12050861
TI  - Immunofluorescence versus ELISA for the detection of antinuclear antigens.
AB  - Determining the presence and specificity of antinuclear antigens (ANA) is a
      challenge to a laboratory involved in the diagnosis of connective tissue disease
      (CTD). The immunofluorescent technique (IF), once considered the gold standard,
      is more and more displaced by ELISA. ELISA can be fully automated and the
      interpretation does not require the extensive experience needed in IF. However,
      literature in which both techniques are compared does not give unequivocal
      conclusions that ELISA indeed performs better. The clue as to which technique is
      best in the cascade testing of ANA, is given by its clinical value, not only by
      its technical and logistic performance. Selective test ordering is strongly
      recommended to increase the predictive value of these tests. The pros and cons of
      both techniques are discussed.

PMID- 12050862
TI  - Molecular diagnosis of HIV.
AB  - The development of molecular techniques that access viral load and the
      development of genotypic resistance have revolutionized the treatment of HIV
      disease. Commercially available viral load assays use a number of different
      approaches from reverse transcriptase PCR to amplification of branched chain DNA.
      The drawbacks of the assay are that there is no international standard that
      allows comparison of viral load between assays and the diversity of different
      clades of HIV results in the under or the nondetection of some patients samples.
      New real-time PCR assays are under development, including LightCycler- and TaqMan
      based tests. The development of sequence-based genotyping assays for the
      detection of mutations associated with the development of the resistance to the
      17 licensed drugs targeted against the pol gene of HIV have added to the
      improvements in patient management. However, next-generation assays must extend
      detection to include the gp41 fusion region and the integrase region of the
      genome as compounds directed against these targets move from clinical trails into
      licensed drugs. Also, genotypic assays must improve detection of minor species
      and detection of sequences from patients with low viral load number. Real-time
      sequence based-diagnostics remains a realistic target within the next 5 years.

PMID- 12050863
TI  - Molecular diagnosis of cystic fibrosis.
AB  - A review of the current molecular diagnosis of cystic fibrosis including an
      introduction to cystic fibrosis, the gene function, the phenotypic variation, who
      should be screened for which mutation, newborn and couple screening, quality
      assurance, phenotype-genotype correlation, methods and method limitations,
      options, statements, recommendations, useful Websites and treatments.

PMID- 12050864
TI  - Moving to nucleic acid-based detection of genital Chlamydia trachomatis.
AB  - Laboratory diagnosis of the bacterium Chlamydia trachomatis has gone through a
      complete phase of evolution since it was first identified as a significant cause
      of sexually transmitted infection. As a fragile, obligatory intracellular
      organism, it was initially only grown in eggs. Subsequently, diagnosis relied on
      culture in continuous cell lines. To address the limitations of culture,
      immunological methods were developed and direct antigen detection using enzyme
      immunoassay and immunofluorescence flourished. With the advent of molecular
      technologies, nucleic acid-based amplification techniques became the methods of
      choice, offering improved standard of care for diagnosis and opening up the
      possibility of screening using noninvasive, patient-acceptable specimens. In this
      article, the various currently available molecular methods are examined, some of
      the existing problems discussed and a view on what we think might happen in the
      next 5 years to the technology and requirement in diagnosis and screening is
      given.

PMID- 12050865
TI  - Determining antibiotic resistance in Helicobacter pylori.
AB  - Resistance development is a significant clinical problem in Helicobacter pylori
      and represents the major cause of treatment failure. Today the problem is most
      focused on the macrolide clarithromycin that is an essential component of the H.
      pylori treatment. Traditional methods for resistance determination, e.g., disc
      diffusion tests or E-tests, could in the next 5 years be replaced by DNA-based
      methods. The most commonly used molecular methods available today are not used in
      the daily routine work. Rapid and reliable DNA-based methods for prediction of
      antimicrobial resistance phenotype are currently available within research. As
      fabrication costs reduce and validated targeted assays are developed with easy
      hands-on procedures, it is most likely that such assays will become important
      tools for clinical diagnosis of resistant H. pylori strains.

PMID- 12050866
TI  - Health care industries' perspective of viral load assays: the VERSANT HIV-1 RNA
      3.0 assay.
AB  - This article will compare the VERSANT HIV-1 RNA 3.0 (bDNA 3.0) assay with other
      HIV-1 viral load assays, particularly the AMPLICOR HIV-1 MONITOR (Amplicor 1.5),
      the industry standard. The discussion will cover the history of viral load assay
      development and challenges to the field. It will finish with a description of the
      evolving markets for viral load assays in the developing world and the impact of
      variations in the different assays on their ability to reach those markets and
      patient populations.

PMID- 12050868
TI  - [Complications of distraction-compression osteogenesis and their prophylaxis--a
      clinical report].
AB  - The authors present a historical overview of various classifications of
      distraction osteogenesis complications. Paley's classification as well as the
      authors' own classification also presented. Basing on the authors' own 10 year
      experiences with the Ilizarov method, selected complications at different stages
      of diagnostics, treatment and rehabilitation are presented. The most effective
      forms of prophylaxis are presented, with special attention given to the surgeon's
      own experience with the Ilizarov method.

PMID- 12050867
TI  - [The influence of osteotomy technique on distraction osteogenesis].
AB  - The authors reviewed the clinical results of leg lengthening by distraction
      osteogenesis, where two different osteotomy techniques were used: classical
      corticotomy according to Ilizarov or osteoclasis. Evaluation of results of 64
      patients were bases on orthopedic examination and detailed X-ray analysis which
      included criteria assessing osseous regeneration rate. In those cases where
      osteoclasis was performed bone formation in the distraction gap was faster than
      in after osteotomy. An accelerated rate of regenerate formation, as well as a
      more active regenerate remodelling was observed. This allowed to shorten the time
      of external fixator application and an earlier rehabilitation.

PMID- 12050869
TI  - [Digital analysis of x-ray pictures in diagnostics and monitoring of post trauma
      reflex sympathetic dystrophy].
AB  - The aim of this paper was to evaluate the digital quality analysis of X-ray
      pictures in patients with post trauma reflex sympathetic dystrophy. Radiograms of
      30 patients were scanned and exposed to optic density analysis. This method
      increases the possibilities of bone pathology interpretation.

PMID- 12050870
TI  - [Range of motion in the joints of the upper extremity at different stages of
      sympathetic reflex dystrophy (SRD)].
AB  - Sympathetic reflex dystrophy of the upper extremity is among the most serious
      complications of trauma injuries. The aim of this paper was to assess the
      effectiveness of mobilization treatment, augmented by cryogenic temperatures of
      post trauma SRD of the upper extremity. The material comprised 113 patients
      treated at the Orthopedic Outpatient Clinic of the J. Babinski Hospital in
      Breslau during the years 1987-1995. All patients underwent conservative treatment
      because of post trauma SRD. The effectiveness of cryo-therapy was based on pre-
      and post-therapy ROM examination. These results were compared to the ROM of the
      healthy extremity and the degree of ROM limitation was hence calculated.
      Limitation of ROM was found in all joints of the upper extremity regardless to
      the stage of the disease. The greatest limitations were found in the joints
      directly adjacent to the area were the disease was most pronounced. The applied
      therapy in these cases was found to increase ROM in all patients, with the
      greatest increase of ROM during stage I and II of the disease.

PMID- 12050871
TI  - [Experience in reconstruction of bony deficits of the acetabulum in total hip
      arthroplasty (THA)].
AB  - The past 40 years have been a period of spectacular advances in the technologies
      related to orthopedic surgery, especially for THA. One of the major problems of
      THA is reconstruction of bony stock deficits of the acetabulum. The material
      consisted of 113 patients aged from 43 to 81 years (average age: 62.5 years), who
      were found to have bony stock deficits and endoprosthesis loosening. In the group
      there were 78 women (average age 65 years) and 35 men (average age 61 years).
      Acetabulum bony stock deficiency was classified according to the Paprosky
      Classification System. Deficits classified as 1st, 2nd and 3rd A grade were
      treated using the X-Change technique, while deficits classified as 3rd B and C
      grade were treated by application of a reinforcing ring and bone packing of
      morselized bone.

PMID- 12050872
TI  - [Five years of experiences with the Antega cementless anatomical stem].
AB  - The aim of this study was to access the changes in bone tissue directly adjacent
      to the Antega cementless stem adaptive remodelling. This stem is corresponds in
      shape to the femoral bone canal. The clinical material comprised a group of 109
      patients aged 32-62 years (average age: 45.5 years), who underwent total hip
      arthroplasty with the Antega stem. The target group consisted of 79 women
      (average age: 45.5 years) and 30 men (average age 49.1). The function of the hip
      was evaluated using Charnley's test. Densitometry was performed basing on
      computer analysis of the X-ray images taken in standard conditions in the antero
      posterior projection. Changes in bone tissue density were assessed using
      Densitometria software. Bone remodelling directly adjacent to the implant was
      correlated to the Antega stem construction. Big changes in bone density in the
      area surrounding the stem with micropore coating may indicate that the intense
      bone remodelling processes are related to the osteoinductive properties of
      micropores and load-transmission to the bone in that area. The stem shaped in
      such a way to correspond to the anatomical shape of the femoral bone showed only
      a very small tendency to create stress shielding zones in its surrounding which
      may indicate that load transmission must closely resemble the physiological one.

PMID- 12050873
TI  - [Development and formation of the hip joint in children with surgically treated
      congenital hip dislocation].
AB  - The aim of this paper was to evaluate the development of different elements of
      the hip joint after surgical treatment, depending on age, anatomic conditions and
      degree of dysplasia at the time treatment was implemented. 100 hip joints were
      evaluated in 76 children treated because of congenital hip dislocation with the
      Dega or Chiari method in the years 1988-1993, according indication proposed
      during the XXVI Conference of the Polish Orthopedic Society. Age of patients at
      the time of surgery ranged from 2.5 to 7.5 years. There were 62 girls and 14
      boys. The Dega method was implemented in 85 joints and the Salter method in 12
      joints. Follow-up period ranged from 5 to 10 years. The best results were
      obtained in children who underwent surgery before 4 years of age.

PMID- 12050874
TI  - [Functional and radiological assessment of the hip joint after Perthes disease].
AB  - Basing a group of 33 patients treat conservatively because of Perthes disease
      some aspects of functional and radiological assessment of the hip joints is
      presented. Functional assessment was performed according to the authors' own
      scale. Radiological assessment was performed basing on Heyman-Herndon method,
      Klisica method and the authors' own head-trochanter factor and head radius
      assessment. A comparison of the obtained results was performed, and the clinical
      usefulness of the authors own head-trochanter and head radius was assessed. The
      head-trochanter factor correlated to the Heyman-Herndon method allowing
      assessment of the proximal epiphysis and physis of the femur, while the head
      radius factor correlated to the Klisica method and allows the assessment of head
      sphericity, head size and the degree of lateral subluxation of the head.

PMID- 12050875
TI  - [Rotation-abduction contracture of the hip joint].
AB  - The paper presents the rotation-abduction contracture of the hip, a problem of
      growing magnitude in recent years. The anatomy of the hip joint, the perils
      related to muscle physiology, the symptoms of the disease, the etiology and means
      of surgical treatment according to Fernandez de Valderrama and Esteve de Miguel
      are discussed. The results of surgical treatment of 12 patients at the Orthopedic
      Department of Wroclaw. The presented procedure has been used in our center since
      1993, and the results encourage further use of this technique.

PMID- 12050876
TI  - [In vivo assessment of bone union by means of monitoring bone healing].
AB  - Basing on personal clinical experiences and available literature I assumed that
      the more advanced bone union is, the less important the role of stabilizing
      instruments in load transfer. At the same time the importance of bone
      consolidation increases. Material consisted of 46 operated patients, who had been
      treated with an external Zespol fixator. To assess load inversion a special
      measuring instrument was constructed. It was found that both the type of
      osteosynthesis and kind of fracture influenced the load inversion process.
      Neutralizing stabilization (group C) gave the shortest bone union time i.e. 22.6
      weeks Average bone union time in contact stabilization was 34.4 and 30.1 weeks,
      depending on fracture type.

PMID- 12050877
TI  - [Anatomical-functional rating system related to pedobarographic examination of
      the foot in patients treated operatively for hallux valgus].
AB  - Author undertook a trial of elaboration of rating system for evaluation of the
      operating treatment results of hallux valgus, in relation to pedobarographic
      examination performed with the use of computed platform PEL-38. 335 feet in 173
      patients (females) treated operatively due to hallux valgus in Orthopaedic
      Department of Wroclaw Medical University in years 1975-1990 were examined. Those
      patients were operated on according to Keller, Dega and McBride method. There was
      elaborated anatomical-functional rating system for the foot. In this system
      different variables were incorporated such as: pain within foot, physical
      activity, walking ability, footwear requirements, hallux valgus angle, callus
      related to forefoot, bunion and MTP joint's ROM. There were distinguished 4
      grades of results: excellent, good, fair and poor, in accordance to number of
      points achieved. Basing on comparison of pedobarographic examination results with
      results of the rating system, definite relation between mentioned above
      evaluating systems was not found.

PMID- 12050878
TI  - [40 years work anniversary of professor Andrzej Walla].

PMID- 12050879
TI  - [Surgery of the hand in Poland--a controversial issue].
AB  - Since hand surgery separated from orthopedic and general surgery as an
      independent subspeciality, the problem of training new surgery came into life.
      Many studies indicate that a country with Poland's population should have about
      250-300 trained hand surgeons. Current estimates show that there are three to
      four times less hand surgeons than necessary. The establishment of the Section of
      Hand Surgery by the Polish Orthopedic Society in 1965 and the founding of the
      Polish Society for Surgery of the Hand (1998) made formal ground for taking up
      both training in hand surgery and assenting it as a separate clinical sub
      category. No official statement has been made in this matter neither by the
      Ministry of Health or by any scientific society. The authors suggest the need for
      organizing a system for training and achieving certified qualifications in hand
      surgery, for example like the FESSH European diploma in hand surgery. It seems
      that this matter should be discussed broadly among both general and orthopedic
      surgeons in order to create a separate sub-category for hand surgery.

PMID- 12050880
TI  - What patients want........

PMID- 12050881
TI  - Restorative management of the worn dentition: I. Aetiology and diagnosis.
AB  - In this, the first of a four-part series on the restorative management of the
      worn dentition, the aetiological factors, diagnosis of toothwear and preventive
      measures are summarized. Later papers will deal with the management of localized
      anterior and posterior toothwear, the use of 'Dahl type' appliances as an
      effective means for the restorations and the various treatment options for the
      management of the dentition showing generalized wear. The series will discuss the
      relative merits of the treatment strategies, clinical techniques and dental
      materials for the restoration of health, function and aesthetics for the
      dentition.

PMID- 12050882
TI  - Facial sinus of dental origin: a case report.
AB  - Sinus tracts of dental origin opening on the skin can be a diagnostic challenge.
      A delay in correctly diagnosing these lesions can result in ineffective and
      inappropriate treatment; however, if recognized early, the sinus tract usually
      resolves after appropriate endodontic therapy or extraction. We report a case of
      a cutaneous sinus tract secondary to a periapical abscess of the mandibular first
      molar tooth. The case was successfully treated by extraction and the sinus tract
      healed.

PMID- 12050883
TI  - Preserving the vital pulp in operative dentistry: 3. Thickness of remaining
      cavity dentine as a key mediator of pulpal injury and repair responses.
AB  - Confusion surrounds the pivotal role played by the remaining dentine thickness in
      a cavity in determining pulpal injury and repair response outcomes after
      restorative treatment. The multifactorial nature of the injury repair response
      requires that attention is focused on the most important factors, including
      remaining dentine thickness, to harness the natural regenerative properties of
      the pulp and to avoid postoperative treatment complications.

PMID- 12050884
TI  - Epilepsy and oral care.
AB  - Epilepsy is a common symptom of an underlying neurological disorder. The seizures
      can take a variety of forms. Both the condition and its medical management can
      affect oral health. Prevention of oral disease and carefully planned dental
      treatment are essential to the well-being of people with epilepsy.

PMID- 12050885
TI  - Assessing restorative dental materials: I. Test methods and assessment of
      results.
AB  - Many methodologies are used during the testing of dental materials. Among these
      are compressive, tensile and flexural strengths, and fracture toughness. However,
      different tests are relevant to different materials and clinical situations. This
      paper describes different test methodologies and discusses the substantiation of
      research claims in publications and advertising.

PMID- 12050886
TI  - Fragile X (Martin Bell) syndrome.
AB  - Fragile X syndrome is a neurodevelopmental disorder that results from a single
      gene mutation on the X chromosome. It is the most common genetic cause of
      learning disability, though many patients remain unrecognized. Fragile X syndrome
      is characterized phenotypically mainly by a long coarse face, prominent ears and
      macro-orchidism. Affected individuals are also mentally challenged and may have
      mitral valve prolapse, and seizures. A case of Fragile X syndrome is reported,
      with oral findings and potential management difficulties in oral care.

PMID- 12050887
TI  - Submerging an endodontically treated root to preserve the alveolar ridge under a
      bridge--a case report.
AB  - The loss of teeth results in the resorption of the residual alveolar ridges. This
      case report describes the successful maintenance of the alveolar ridge contour in
      the maxillary anterior region under a fixed prosthesis by the mucosal coverage
      and submersion of an endodontically retreated root, including a 6-year follow-up.

PMID- 12050888
TI  - Arboreal locomotor adaptation in primates and its relevance to human evolution.
      Proceedings of a workshop. March 5-7, 1999.

PMID- 12050889
TI  - Air trapping and arboreal locomotor adaptation in primates: a review of
      experiments on humans.
AB  - A review was made of experiments on humans in which air trapping by glottis
      closure during three-dimensional movements were examined in four subjects
      including former Olympic gymnasts. In brachiation and horizontal bar exercises,
      the behaviour of the larynx was monitored with a fiberoptic endoscope, and EMG
      data were recorded from shoulder muscles. The results revealed that
      immobilization of the polyaxial connection between the shoulder girdle and the
      thorax by air trapping occurs in phases of extreme loading of the upper limbs.
      The closure of the airway by the larynx in humans serves three functions: first,
      the prevention of errors in deglutition; second, the production of vocal sounds;
      third, the retention of air inside the thoracic cavity. The latter function, air
      trapping, allows the immobilization of the rib cage for the muscular fixation of
      the shoulder blade on the trunk in movements that imply unusually high external
      forces acting on the upper limbs. This morphological-functional innovation
      probably has been made when early mammals invaded the three dimensional arboreal
      habitat, because it gave the tree-dwelling early primates the device to anchor
      themselves by the arms alone and to avoid falling out of trees. The specific
      functional characteristic of primates is the hermetic closure of the vocal and
      vestibular folds by rapidly contracting muscles in the folds. So the closure of
      the glottis, which in humans seems primarily an adaptation to the production of
      vocal tones, seems to go back to the adaptation of Tertiary arboreal primates to
      movements in a three-dimensional environment. Our conclusions are in agreement
      with the results of other contributions to this volume.

PMID- 12050890
TI  - Composition of myofiber types in the vocalis muscles involved in rapid closure of
      the glottis in Japanese macaques.
AB  - Myofiber types of the medial thyroarytenoid (vocalis) muscle, lateral
      thyroarytenoid muscle, and cricothyroid muscle of the Japanese macaque were
      examined with enzyme-histochemical methods. For comparison, the semitendinosus
      muscle of the Japanese macaque and the thyroarytenoid (vocalis) muscle of cattle,
      sheep, and pig were examined with the same methods. The vocalis muscle of the
      Japanese macaque was composed exclusively of fast-twitch/oxidative/glycolytic
      (FOG) myofibers; it differed from the lateral thyroarytenoid, cricothyroid, and
      semitendinosus muscles of the Japanese macaque and from the vocalis muscles of
      the other animals, which consisted of slow-twitch/oxidative, FOG-, and fast
      twitch/glycolytic myofibers or type IIC myofibers. The histochemical properties
      of the vocalis muscle of the Japanese macaque show that the vocalis muscle has a
      capacity to close the glottis rapidly and completely.

PMID- 12050891
TI  - What does "arboreal locomotion" mean exactly and what are the relationships
      between "climbing", environment and morphology?
AB  - The characteristics of "climbing" in the sense of locomotion or posture on three
      dimensional substrates are discussed from a biomechanical viewpoint. For this
      purpose, the mechanical conditions of the most widely spread modes of locomotion
      or gaits used in arboreal surroundings are reviewed. This allows precise
      identification of morphological characteristics of traits that are advantageous,
      and therefore have a positive selective value. Further, at least some of the
      environmental and substrate characteristics that need to be present for using a
      specific gait, are noted. It turns out that the extremity which is placed lower
      on the substrate, has to carry a higher load. If this extremity is consistently
      the hindlimb--which actually is the case in primates, because of understandable,
      though complex reasons--a division of labor is likely to occur between the limbs:
      the hindlimb becoming stronger and the forelimb weaker, but more versatile. A
      very specific, and advantageous feature of the primates is their possession of
      prehensile hands and feet. That means the autopodia are able (1) to produce by
      themselves, without the aid of body weight, very high frictional resistance, and
      (2) to transmit tensile forces as well as torsional moments on the substrate. The
      above-mentioned division of labor between fore- and hindlimbs implies that the
      former make the first contacts with and explore the properties of parts of the
      environment. As a next step, prehensile hands on long arms may easily replace
      length and mobility of the neck in getting hold of food items. So very
      characteristic traits of human body shape can be derived to a large extent from
      the necessities of arboreal locomotion: Prehensile hands, long arms,
      concentration of body weight on the hindlimbs, shortness of the trunk in
      comparison to limb length.

PMID- 12050892
TI  - The effects of substratum inclination on locomotor patterns in primates.
AB  - To explore the change from the horizontal quadrupedal walking to the vertical
      climbing in primates, I designed an experiment on an inclined substratum. The
      subjects were an adult male Japanese macaque and a 2-year-old female white-handed
      gibbon. The animals moved on a substratum made of bamboo pipe (8 cm diameter).
      The inclination of the substratum was changed from 15 degrees to 65 degrees in 5
      degree increments for the Japanese macaque and from 20 degrees to 70 degrees with
      10-degree increments for the white-handed gibbon. I placed surface electrodes and
      telemetry transmitters on the subjects to record the activity of the long head of
      the triceps brachii and the long head of the biceps brachii muscles. The Japanese
      macaque utilized horizontal quadrupedal walking until the incline was 15 degrees.
      Vertical climbing began at an inclination of 55 degrees. The intermediate
      locomotor mode was observed between 20 degrees and 50 degrees. The white-handed
      gibbon changed the locomotor mode from horizontal quadrupedal walking to vertical
      climbing at 40 degrees. I believe that the difference observed in locomotor mode
      between these two species was mainly due to differences in the intermembral
      index. The white-handed gibbon had a large intermembral index, which meant she
      had longer forelimbs and could therefore change locomotor mode at a lower
      inclination of the substratum.

PMID- 12050893
TI  - Primate limb bones and locomotor types in arboreal or terrestrial environments.
AB  - Postcranial limb bones were compared among primates of different locomotor types.
      Seventy-one primate species, in which all families of primates were included,
      were grouped into nine locomotor types. Osteometrical data on long bones and data
      on the cross-sectional geometry of the humerus and the femur were studied by
      means of allometric analysis and principal component analysis. Relatively robust
      forelimb bones were observed in the primate group which adopted the relatively
      terrestrial locomotor type compared with the group that adopted the arboreal
      locomotor type. The difference resembled the previously reported comparison
      between terrestrial and arboreal groups among all quadrupedal mammals. The degree
      of arboreality in daily life is connected with the degree of hindlimb dominance,
      or the ratio of force applied to the fore- and hindlimb in positional behaviour
      and also with the shape, size and robusticity of limb bones.

PMID- 12050894
TI  - The importance of the evolutionary heritage of locomotion on flat ground in small
      mammals for the development of arboreality.
AB  - The earliest representatives of the mammalian stem line were small. Recent small
      mammals preserving their morphology possess rather similar kinematic and dynamic
      locomotor patterns, even if they are not closely related. For a small animal, the
      mechanics of locomotion on a large branch is comparable to locomotion on flat
      ground. Combining these informations, it seems sensible to start a discussion on
      the origins of arboreality with a detailed analysis of the locomotion of small
      mammals on flat ground. For this purpose, the kinematics of twelve species of
      mammals were observed using cineradiography, a "general limb" of small mammals
      was derived as a principle, and its interactions with the trunk were analyzed.
      These data form the basis for a theoretical upscaling of the motion patterns in
      arboreal animals, revealing that the transfer of torques between animal and
      branch becomes unavoidable, thus making the use of prehensile hands advantageous,
      which by their tendency of distal concentration of muscle masses force the need
      to change the basic kinematic patterns.

PMID- 12050895
TI  - Shoulder movements during quadrupedal locomotion in arboreal primates.
AB  - The kinematics of scapula and shoulder joint movements were analyzed in three
      species of arboreal quadrupedal primates using cineradiography. Our findings
      indicate that scapular movement is highly important for forelimb movement in
      primates with this ancestral mode of locomotion. Retroversion of the scapula
      (syn. caudal rotation or extension) during the stance phase contributes more than
      40% to the stride length of the forelimb. Lateral forelimb excursions, a general
      feature for arboreal primates, are based on complex three-dimensional scapular
      movements guided by the clavicle. Humeral abduction is achieved by scapular
      abduction and transversal rotation of the scapula about its longitudinal axis,
      and is therefore strikingly different from humeral abduction in humans. At the
      same time, the movements of the shoulder joint are limited to flexion and
      extension only.

PMID- 12050896
TI  - Arboreal locomotion in small new-world monkeys.
AB  - The postural and locomotor activity and its relation to substrates was observed
      in 3 Saguinus oedipus, and 3 Saimiri sciureus for comparison, during a period of
      10 h for each individual. The animals moved freely in cages of 3.40 m x 3.40 m x
      2.40 m (height) on rather diverse substrates. Observations were made according to
      the focal-animal-method, with combined instantaneous and continuous sampling.
      They were protocoled in schematic form and video-recorded. In addition, 3 further
      Saguinus oedipus were subjected to an X-ray cinematographic study on a modified
      treadmill to unveil metric parameters of the locomotor pattern preferred on
      slender and compliant ("arboreal") substrates, the walk. Independent from the
      substrates, the postures of the two species differed in details, as do the
      preferred substrates. Horizontal, comfortable substrates are favored most.
      Walking ranked top in frequency, followed by jumping and galloping (in a strict
      sense). All other locomotor modes described for primates played a minor role or
      lacked entirely, like the trot. Average distance of leaps was only 0.60 m,
      landings were mainly on the same level as take-offs. In Saguinus, the movements
      of both limbs, including the shoulder blade, followed the pattern common to small
      mammals in general: At the end of the stance phase, humerus and tibia are nearly
      parallel to the substrate, while just before touchdown ulna and femur are in this
      position. The walk in both species was surprisingly fast (1 m/s), reaching the
      speed of much larger cursorial animals, like humans.

PMID- 12050897
TI  - Reconstructing the mechanics of quadrupedalism in an extinct hominoid.
AB  - Traditionally, analogising comparative anatomical approaches, working on features
      of individual bony elements, have led to the Miocene hominoids Proconsul heseloni
      and P. nyanzae being described as arboreal, with a variety of possible locomotion
      modes. Whilst most researchers seemingly agree that quadrupedal was one of the
      most frequently adopted modes, any deeper knowledge about the kinematical
      characteristics of such quadrupedalism is very limited. Based on the previous
      studies and a computer simulation technique developed in our laboratory, a set of
      alternative models for Proconsul quadrupedalism was created. The body
      measurements and initial properties for the different models were held constant,
      using data from published literature if available, or otherwise estimated from
      data for Pan. Judged by the power output of joints, the results of computer
      simulation indicate that the style of quadrupedal locomotion typical of living
      macaques fits the body proportions of Proconsul better than that of Canis
      domesticus, Varecia variegata, Cebus albifrons or Pan troglodytes. It may
      reasonably be assumed that Proconsul's quadrupedal mode was similar to that of
      living macaques.

PMID- 12050898
TI  - Radio-ulnar deviation of the primate carpus: an X-ray study.
AB  - The lack of contact between the ulna and first row of carpals characterizes the
      wrist morphology of hominoids as compared to other primates. This distinctive
      feature--generally interpreted as a significant synapomorphy between humans and
      other hominoids--was a priori considered to be an indication of an increased
      capacity for ulnar deviation, allowing a greater diversity of hand movements.
      This X-ray study aimed to test this hypothesis by comparing the shifting of the
      carpals throughout radioulnar deviation in eight extant genera endowed with ulno
      carpal contact or lacking it. The results show that the amplitude of ulnar
      deviation is not directly correlated with the presence or absence of an ulno
      carpal contact: most ulnar deviation takes place at the antebrachio-carpal joint
      in those primates that lack an ulno-carpal contact (hominoids), instead of at the
      mid-carpal joint in primates whose ulna articulates with the triquetral
      (cercopithecoids, platyrrhines, most strepsirrhines). Analysis of the X-ray
      suggests that the loss of ulno-carpal contact improved the ability to supinate at
      the radio-ulnar joints, with correlated unfitness for palmigrade/semidigitigrade
      walking. This evolutive change, associated with a considerable reduction of the
      share of body weight carried on the forelimbs, likely cleared the way for either
      knuckle walking or bipedalism and handiness.

PMID- 12050899
TI  - The insertions of the cruropedal muscles and implications for the locomotor
      evolution in primates.
AB  - We examined gross-anatomically the cruropedal muscles, which control the toe
      movements, in some species of insectivores, rodents and primates including
      humans, with a focus on the phylogenetic developments of these muscles including
      the distribution patterns of the tendons to the toes. Morphological changes
      corresponding to the phylogenetic advancement from primitive terrestrial mammals
      to arboreal primates were found in the short extensors and flexors, presumably in
      association with the enhancement of independent digital mobility. In contrast,
      the changes which correspond to the acquisition of terrestrial bipedality in
      humans were identified in the development of extensors and flexors which govern
      the first toe, as well as in establishment of the peroneus tertius that dorsi
      flexes the talocrural joint.

PMID- 12050900
TI  - Composition of psoas major muscle fibers compared among humans, orangutans, and
      monkeys.
AB  - In primate species the m. psoas major, the only muscle simultaneously controlling
      the spinal column and lower extremity, is expected to reflect morpho-functional
      adaptation to diversified locomotor behavior. By using histochemical analysis
      with Sudan black B staining, composition of different types of muscle fibers in
      the psoas major was compared between 2 Japanese macaques, 2 hamadryas baboons, 2
      anubis baboons, 2 orangutans, and 17 humans. The comparison has revealed unique
      features of this muscle in humans: 1) Type 1 or red fibers are thicker than Type
      2 or white fibers in humans but vice versa in nonhumans; 2) among the species
      examined the number of the muscle fibers per unit cross-sectional area is
      largest, implying the fibers are thinnest, in humans; 3) frequency of Type 1
      fibers is highest in humans, intermediate in monkeys, and lowest in the
      orangutan, whereas Type 2 fibers show an inverse trend among the species. These
      results suggest a correspondence in primates between the composition of the psoas
      major muscle fibers and difference in substrates inhabited as well as in their
      positional behaviors.

PMID- 12050901
TI  - Effects of fixation and preservation conditions on immunohistochemical profiles
      of the skeletal muscle fibers in Japanese macaques.
AB  - Effects of fixation and preservation conditions of muscle tissues on
      immunohistochemical profiles are investigated. Samples of the hind limb and
      epaxial muscles were removed from 4 adult female Japanese macaques (Macaca
      fuscata) fixated with 10% formalin and preserved in the same solution under
      different conditions for 6 months to 4 years and 6 months. Sections were stained
      with indirect immunofluorescence and avidin-biotin peroxidase complex methods
      using an antibody against fast myosin (Mouse Monoclonal Anti-skeletal Myosin
      Fast, clone MY-32, Sigma) as a primary antibody. Clear responses to the antibody
      were demonstrated in the samples from the specimens fixated by injection or
      immersion with 10% formalin and preserved in the same solution for 6 months to 1
      year and 6 months. Distribution patterns of the fibers reacting to the antibody
      coincided with that of the fast twitch fibers determined using enzyme
      histochemical techniques in these samples. Clear responses to the antibody were
      not demonstrated in the samples from the specimen repeatedly rinsed in water for
      gross anatomical dissections during the preservation period. The results of this
      study warrant applications of immunohistochemical techniques to the study of
      fiber type composition in muscle samples from specimens fixated with formalin and
      preserved in the same solution for a long term.

PMID- 12050902
TI  - Suspensory behavior and its role in positional activities of Japanese macaques.
AB  - Suspensory behavior of free-ranging Japanese macaques was classified based on the
      kinematics and situations, and incidence of the behavior recorded with the
      continuous focal animal sampling method was compared between different age
      groups. Of all age groups, infants used the various types of suspension most
      frequently, and the frequency declined rapidly with age. Suspension was used as
      1) a safety device by infants, to prevent falling down from supports when losing
      balance, 2) a feeding posture and 3) a supplement for shortage of the reaching
      length composed of limbs and trunk lengths in young macaques. The roles of
      suspensory behavior in the development of positional activities in Japanese
      macaques are briefly discussed.

PMID- 12050903
TI  - Palaeoenvironments and hominoid evolution.
AB  - One of the key features that separates humans and their closest relatives
      (extinct species of the genus Homo and Praeanthropus and the australopithecines
      Australopithecus and Paranthropus) on the one hand, from the other hominoids, on
      the other, is their obligate bipedal locomotion when on the ground. This major
      difference from the generally quadrupedal locomotion practiced by other hominoids
      (Pan, Gorilla, Pongo and many extinct lineages) is reflected in many parts of the
      body, including all the major bones in the legs, arms, trunk and cranium.
      Locomotion has thus been of major interest to those interested in human origins,
      evolution, classification and phylogeny. A major hurdle to studies of the origins
      of bipedalism concerns the paucity of African hominoid fossils between 15 Ma,
      when all the adequately known hominoids were quadrupedal (most were pronograde,
      but at least one lineage was orthograde), and 4.2 Ma by which time fully bipedal
      hominids were established in Africa. Examination of Old World geology and
      palaeontology reveals a great deal about the evolution of palaeoenvironments and
      faunas during this period, and it is suggested that hominids evolved bipedal
      locomotion at the same time that there was a fundamental reorganisation of faunas
      towards the end of the Miocene. This faunal turnover resulted in the
      establishment of faunal lineages of "modern" aspect in Africa at the expense of
      "archaic" lineages which either went extinct or suffered a diminution of
      diversity. Many of the "modern" lineages were adapted to open country habitats in
      which grass became a major component of the diet as shown by modifications in the
      cheek teeth. Hominoids, in contrast, retained their traditional diet but were
      obliged to forage over greater and greater areas in order to do so, and this
      tactic led to pressures to modify the locomotor system rather than the diet. If
      bipedal hominids originated during this period, then the family Hominidae (sensu
      stricto) dates from about 8-7 Ma.

PMID- 12050904
TI  - From apes to humans: locomotion as a key feature for phylogeny.
AB  - If bipedalism has often been considered to be of a crucial interest for
      understanding hominid evolution, the acceptance of locomotor features to build
      phylogenies is still far from being a reality in the field. Especially for
      hominid evolution, it still seems to be difficult to accept that traits, other
      than craniodental ones, can be useful for defining the major dichotomies. The
      recent discovery of Australopithecus anamensis suggests a challenging view of the
      major dichotomy between apes and humans. Whilst it is widely accepted that
      Ardipithecus ramidus is ancestral to Australopithecus anamensis, which in its
      turn is ancestral to Australopithecus afarensis and then to later hominids, the
      postcranial adaptations, which should be taken into account, suggest another
      branching pattern. Based on the fact that by 4.0 million years two different
      locomotor patterns can be identified in hominids, two lineages would appear to be
      present: the "Australopithecine" lineage (with Australopithecus afarensis or
      Ardipithecus ramidus if the latter is really a hominid sensu stricto) and the
      "Hominine" lineage (with Australopithecus anamensis = Praeanthropus africanus).

PMID- 12050905
TI  - Morphology of the hallucial phalanges in extant anthropoids and fossil hominoids.
AB  - Pedal phalanges of living anthropoids and several Miocene fossil hominoid taxa
      were studied to reveal functional adaptations of living anthropoid feet and to
      infer positional behavior of fossil hominoids. Among the examined living
      anthropoids, Pan has a very developed (long and robust) hallux. Proconsul and
      Nacholapithecus, a large hominoid from Nachola, northern Kenya, display a
      moderately long hallux like Alouatta and Cebus, suggesting the well-developed
      capability of a hallux-assisted power grip. Allometric analyses revealed that the
      Miocene hominoids examined (mainly from East Africa) as a whole displayed a
      different scaling pattern about the width of the proximal articular surface of
      the hallucial terminal phalanx from that of living anthropoids. Larger-sized
      hominoids display a wider articular surface than comparable-sized living
      anthropoids while smaller-sized fossil hominoids do the reverse. Such a
      difference was less marked for the height of the articular surface. These results
      may suggest that positional adaptations of Miocene hominoids are not merely
      resultants of a common body size function that is observed in living anthropods.
      The wide articular surface of fossil hominoid hallucial terminal phalanges
      suggests an adaptation for vertical climbing and clinging, in which the hallux is
      kept perpendicularly to the long axis of the vertical support.

PMID- 12050906
TI  - Cross-sectional geometric properties along the diaphysis of femur and humerus in
      chimpanzees and humans.
AB  - The cross-sectional geometric parameters were determined serially along the
      diaphysis of 3 paired humeri and femora of chimpanzees by using the computed X
      ray tomographic scans, and compared with those of humans. In magnitude, the
      femoral parameters were greater and humeral parameters were less, respectively,
      in humans than in chimpanzees. While the changing pattern among the parameters
      along the diaphysis was very similar both in the femur and humerus of
      chimpanzees, the pattern in the humans was reversed between the cross-sectional
      area and area moments of inertia. In chimpanzees, the femoral parameters
      increased toward the most proximal diaphysis, whereas humeral parameters yielded
      a moderate peak in a portion slightly proximal to mid-shaft. Potential mechanisms
      responsible for these findings were discussed.

PMID- 12050907
TI  - Kinematics and ontogeny of locomotion in monkeys and human babies.
AB  - Early ontogenetic stages are often assumed to reflect or to be similar to past
      phylogenetic stages within the evolution of man. Therefore, as a first step, the
      quadrupedal crawling locomotion of human children was analysed and compared to
      the quadrupedal walk of Macaca fascicularis. The movements of the human child
      were not only more irregular, they differed from the walk of the monkey mainly
      through extraordinarily short swing phases, and also through strong scoliotic
      movements of the spine. There is a compulsory synchronisation in the hip and knee
      joint movements of the human crawling baby. We conclude that human crawling may
      be a behavioural recapitulation of a quadrupedal evolutionary stage. However,
      with reference to kinematics, man is not only characterised by his unique,
      habitually bipedal, upright gait but also by a second, equally unique locomotion,
      namely crawling, which he assumes for a short phase during his first year of
      life.--The walking movements of the limbs in toddling infants were mainly
      characterised by i) rather stiff, abducted arms, which were moved mostly by spine
      torsions (similar to those of bipedally walking Gorilla) and not as a suspensory
      pendulum. However, they rather work as levers for the elastic torsion pendulum of
      the spine. ii) They are also characterised by frequently lacking the minor knee
      flexion, which occurs at about the heel strike within each stride of the adult
      human. Besides many other details of the results, foot movements differed from
      adult ones mainly in that the whole plantar surface was placed flat on the ground
      within a few milliseconds.

PMID- 12050908
TI  - [Antiretroviral therapy].
AB  - The use of combinations of antiretroviral drugs can profoundly suppress HIV
      replication for prolonged periods and has substantially decreased AIDS-related
      morbidity and mortality. The optimal use of antiretroviral drugs remains a
      rapidly evolving field and numerous obstacles need to be addressed. Many regimens
      are associated with substantial toxicity, large pill burdens and high cost. In
      addition, it has become clear that currently available regimens cannot completely
      suppress HIV replication. Nevertheless, the goal of antiretroviral therapy
      remains the suppression of plasma viremia as much as possible for as long as
      possible. Additional goals of therapy include restoration and preservation of
      immune function, minimization of toxicity, to prevent the disruption of lifestyle
      and the emergence of drug-resistance virus strains. In some patients a sustained
      elevations in CD4 cell counts occur despite incomplete viral suppression during
      HAART. The optimal therapeutic approach in these patients is still unclear. If,
      as it is generally assumed, viral load determinations reflect ongoing viral
      replication, then the evolution of drug resistance might be expected. Thus, to
      prevent the emergence of multidrug resistance, also in these patients a change to
      a salvage therapy is a viable option.

PMID- 12050909
TI  - [Anti-IgE antibodies in the treatment of bronchial asthma].
AB  - The central role of IgE in the pathogenesis of bronchial asthma has induced to
      study the effects of a monoclonal antibody anti-IgE in this disease. The
      characteristics of this antibody and the early results of its use in bronchial
      asthma are briefly summarized.

PMID- 12050910
TI  - [Appropriateness of requests of echo-color-Doppler tests].
AB  - Technological development of ultrasound has allowed diagnosis of diseases that
      one would be able to see later. These easy and harmless examinations have
      produced an increasing in demand not always justified, as one could think to
      reach simply a shining diagnosis. The authors evaluated the appropriate use of
      each color-doppler sonography request in agreement with published guidelines.
      Nine hundred eighty six requests were examined in three months: 60.2% of them
      were not appropriate. Carotid-vertebral arteries were the group with higher
      inappropriate use (67.9%) and also the urgent exams have 21.9% of inappropriate
      use. When clinical reason was missing in the request, the inappropriate use
      reached 70%. The 52.9% of examinations have not revealed any vascular pathology
      and among appropriate exams the 31.7% was disease free. Although angiology
      clinical guidelines have been recently published in Italy, the data suggest a
      poor clinical valuation of suspected vascular patient (70% of not appropriate
      examination when clinical problem was lacking); this may be the answer for both
      the enormous color-doppler requests, high inappropriate use and normal results.
      Authors think that a way to lower this high grade of color-doppler exams may be
      to take in appropriate consideration clinical approach, fact that also permit a
      correct interpretation of ultrasonographic data.

PMID- 12050911
TI  - [Lipid profile in hematologic neoplasms].
AB  - BACKGROUND AND OBJECTIVE: Abnormal blood lipid profiles have been reported in
      human malignancies. So, it is likely an overall involvement of tumoral cell
      metabolism. The aim of this study was to evaluate clinico-biological implications
      of altered lipid profiles in oncohaematologic patients. DESIGN AND METHODS: The
      plasma lipids, lipoproteins and apolipoproteins were determined at the time of
      diagnosis in 48 previously untreated patients (35M, 13F, median age 60 years), 11
      with multiple myeloma (MM), 11 with non-Hodgkin's lymphoma (NHL), 11 with acute
      leukemia (AL), 10 with chronic myeloproliferative disorders (CMD) and 5 with B
      chronic lymphocytic leukemia (B-CLL). The results were correlated with known
      prognostic serum markers, such as lactate dehydrogenase (LDH), beta-2
      microglobulin (beta 2m), and soluble molecule ICAM1 (sICAM1). RESULTS: Altered
      blood lipid profiles were observed in all concohaematologic patients.
      Statistically significant values included reduced cholesterol (155 +/- 47.36 vs
      205 +/- 35 mg/dl; p < 0.001), HDL-C (30.47 +/- 13.36 vs 45 +/- 10 mg/dl; p <
      0.003) and apo A (118.86 +/- 49.98 vs 182.69 mg/dl; p < 0.0001) levels. No
      correlations were found between cholesterol levels and clinico-biological
      features representative of tumor mass (LDH, beta 2m, sICAM-1). A significant
      increase of cholesterol levels was observed in all patients responding to
      therapy. INTERPRETATION AND CONCLUSION: These results support the idea that the
      cholesterol, its fractions and the apolipoproteins determinations might be
      considered as useful biochemical and prognostic markers in hematologic neoplasms.

PMID- 12050912
TI  - [Hepatocarcinoma in HCV compensated correlated liver cirrhosis: role of treatment
      with interferon].
AB  - The hepatocarcinoma (HCC) represents one of the major causes of morbidity and
      mortality in course of chronic HCV correlated hepatopathy. Up to today there are
      no reliable therapies which can delay or avoid the arising of HCC, nonetheless
      various Authors have noticed a decrease of such incidence in the subjects treated
      with interferon (IFN). Such encouraging results have not yet found univocal
      confirmation in course of compensated cirrhosis (Child-Pugh A). In our experience
      a cohort of 122 patients prospectively followed was analysed retrospectively to
      asses the effect of IFN therapy (mean follow-up 96 +/- 18.3 months). We conducted
      a randomized study in compensated cirrhosis with abnormal ALT and HCV-RNA
      positive serum (post-transfusional infection). Fifty-nine patients (mean age 55.3
      +/- 7) received IFN (3 MU three times a week for 12 months) (8 stopped therapy
      for side effects), 71 did not receive IFN (mean age: 56.8 +/- 8). Baseline
      characteristics were similar. IFN therapy does not reduce the risk of HCC in
      compensated cirrhosis. In IFN treated patients it has been noted an improvement
      in relation with worsening and death/OLT. Moreover, in the non responder group,
      the number of negative events has been higher than in the sustained responder
      group and in subjects with relapse. On the contrary, no particular differences
      have been noticed in relation with the arising of HCC. It can be hypotized that
      the therapy with IFN does not reduce the risk of HCC in compensated cirrhosis.
      Such condition represents by itself a risk factor. It can be concluded that the
      therapy with IFN can be effective in reducing the possibility of clinical
      laboratoristic worsening. However, even in case of substained response, the
      follow-up for the arising of HCC must always be done.

PMID- 12050913
TI  - [p-ANCA and ASCA antibodies in the differential diagnosis between ulcerative
      rectocolitis and Crohn's disease].
AB  - Anti-Saccaromyces cerevisiae antibodies (ASCA) seem to be associated with Crohn's
      disease (CD), while anti-neutrophil cytoplasm antibodies (p-ANCA) seem to be a
      recognised marker for ulcerative colitis (UC). AIM: Of our study was to determine
      whether the presence of ASCA and p-ANCA antibodies could differentiate CD from UC
      and IBD from aspecific chronic colitis (ACC). METHODS: Serum samples were
      obtained from 23 patients with CD and 32 with UC, and from 13 patients with
      aspecific chronic colitis. Diagnosis was established on clinical findings,
      endoscopy and histology. Determination of ASCA and p-ANCA antibodies was
      performed using indirect immunofluorescence technique and ELISA, respectively.
      RESULTS: 20% CD patients against 50% UC patients expressed p-ANCA (p < 0.05).
      Vice versa 61% CD patients against 16% UC patients expressed ASCA (p < 0.05). The
      combination of positive ASCA and negative p-ANCA determined a sensibility,
      specificity and positive predictive value of 45%, 91% and 75% respectively, for
      diagnosis of CD. The combination of positive p-ANCA and negative ASCA determined
      a sensibility, specificity and positive predictive value of 44%, 95% and 94%
      respectively, for diagnosis of UC. CONCLUSION: Our results indicate that ASCA are
      principally expressed in patients with CD, by contrast p-ANCA seem to be strongly
      associated with UC. The combination of these two tests can be useful in
      evaluating patients with indeterminate colitis, distinguishing UC from CD.

PMID- 12050914
TI  - [Primary septic arthritis of the sterno-clavicular joint].
AB  - Septic arthritis of the sternoclavicular joint (SCJ) is an uncommon form of
      arthritis generally occurring in immuno-compromised patients with contiguous or
      distant foci of infection and central venous catheters. Septic SCJ arthritis in
      previously healthy subjects is a very rare occurrence requiring a high index of
      suspicion for the diagnostic assessment. We report here one patient without
      predisposing factors presenting Staphylococcus aureus SCJ infection.

PMID- 12050915
TI  - [Lung carcinoma. An unusual case of survival].
AB  - Lung cancer incidence is continuously increasing over the world, despite
      significant advances in both the diagnostic and therapeutic fields. At the
      diagnosis, more than 2/3 of patients present a locally advanced disease
      associated with a 5-year survival of less than 35%, or with distant metastases
      associated with no long-time survival. Chemotherapy with cisplatin remains a well
      established option in the treatment of lung cancer, as confirmed by recent meta
      analyses, and its action seems strengthened by the introduction of new agents
      (taxans, gemcitabine, vinorelbine, topotecan, and others), that are giving
      promising results for a better control of this disease.

PMID- 12050916
TI  - [Risk factors of transient cerebral ischemic episodes: hyperfibrinogenemia and
      carotid histopathology].
AB  - Risk factors may play a fundamental role in the evolution from a stable to a
      vulnerable plaque. In particular, the hyperfibrinogenemia, independently from
      other risk factors, influences the natural history of cerebrovascular disease
      modifying the histologic composition of atherosclerotic plaques and precipitates
      carotid thrombosis resulting from rupture of the plaque. Determination of plasma
      fibrinogen may help to identify a subset of patients at high risk for a rapid
      progression of carotid atherosclerosis and related clinical events. We suggest
      that these patients may benefit of an earlier surgical intervention even if the
      degree of carotid stenosis is not severe.

PMID- 12050917
TI  - [Hepatitis C virus and pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic inflammatory interstitial lung
      disease characterized by an accumulation of alveolar macrophages and neutrophils
      in the lower respiratory tract, parenchymal injury, and interstitial fibrosis.
      Although the etiology of IPF is unknown, it has been suggested that viral agents,
      among which hepatitis C virus (HCV), may be involved in inducing the disease. In
      patients with chronic hepatitis HCV+ and in those with mixed cryoglobulinemia HCV
      associated, HCV may trigger a subclinical lymphocyte alveolitis. Furthermore,
      pulmonary fibrosis associated with a variety of rheumatic disorders has been
      reported in 8/300 patients with active chronic hepatitis HCV+. Bronchoalveolar
      lavage, carried out in 4/8 patients, showed an increased percentage of
      neutrophils in all of them and a mild increase of lymphocytes in 2 patients.
      Thoracoscopic lung biopsy was carried out in 2 patients and showed a desquamative
      interstitial pneumonia; in one case HCV-RNA was found in the pulmonary
      parenchyma. Although the above observations seem indicate a role for HCV in IFP,
      further studies are required to define its true importance in the
      etiopathogenesis of the interstitial lung disease.

PMID- 12050918
TI  - [Alternative tests in the diagnosis of food allergies].
AB  - In the last years an increase of allergic diseases has been observed whose
      prevalence is about 20-30% in general population of western countries. However
      there is a risk of an over diagnosis of allergic diseases as many different
      diseases (migraine, chronic urticaria, chronic inflammatory bowel diseases,
      chronic-fatigue syndrome etc.) are considered due to food allergy or intolerance.
      In many patients the diagnosis is based on the results of alternative diagnostic
      tests such as the cytotoxic test, the provocation/neutralization sublingual or
      subcutaneous test, the heart-ear reflex test, the kinesiology, the biorisonance,
      the electro-acupuncture, and the hair analysis, or on immunological tests
      (immunocomplex or specific food IgG). We reviewed the scientific evidences of
      these tests (specificity, sensibility, rationale, reproducibility). According to
      most studies none of them had to be recommended as useful for the diagnosis of
      food allergy or intolerance. Physicians should alert patients about the risk of
      an indiscriminate use of these test in the diagnosis of food allergy. In fact the
      use of an incorrect diet could be dangerous, particularly in childhood, as
      recently shown.

PMID- 12050919
TI  - [LIFE-study: losartan reduces cardiovascular risk factors more than atenolol].

PMID- 12050921
TI  - [Medication in neurologic patients. Considerations for acute and chronic drug
      therapy].

PMID- 12050920
TI  - [Chronic-obstructive pulmonary disease. Medical treatment].

PMID- 12050922
TI  - [Osteoporosis: prevention, diagnosis and therapy].

PMID- 12050923
TI  - [Vitamins--what is really useful?].

PMID- 12050924
TI  - Surveillance, addiction, and policy: the examples of South Africa and
      Afghanistan.

PMID- 12050925
TI  - [Changes in the age of onset of cannabis use: results of the 2nd Swiss Health
      Survey 1997].
AB  - OBJECTIVES: Based on data from the second Swiss Health Survey conducted in 1997,
      the present study investigates changes in the onset of cannabis use and
      associated consequences. METHODS: Telephone interviews were conducted with 7743
      individuals aged 15 to 49 years. Life time prevalences, onsets of illicit drugs
      use, and cessation of cannabis use were investigated. RESULTS: Using survival
      analysis, the study shows that, in Switzerland onset into the use of cannabis has
      decreased by almost nine months between 1992 and 1997 down to 15.83 years old. An
      early onset is associated with higher prevalences of other illicit drug use
      (e.g., cocaine, ecstasy, hallucinogens), and early onsets into the use of these
      drugs. Similarly, cessation of cannabis use is less frequent in early onset
      users. CONCLUSION: Results are discussed in the light of increasing prevalences
      of cannabis use and the discussion about an increasing legalization, respectively
      depenalization, of cannabis use in Switzerland.

PMID- 12050926
TI  - Decreasing intravenous cocaine use in opiate users treated with prescribed
      heroin.
AB  - OBJECTIVES: Providing maintenance treatment for heroin users who also use cocaine
      presents special problems. Poly-drug use is prevalent among clients in the Swiss
      Program for the Medical Prescription of Heroin (1994-1996). METHODS: A formative
      evaluation examines whether cocaine use was associated with a higher drop-out
      rate from treatment, and how cocaine use changed among those who remained in
      treatment. Frequency of cocaine use before and during treatment was measured by
      self-report every six months and by urinalysis every two months. RESULTS: There
      was no significant difference between the drop-out rates for cocaine users vs.
      non-users (n = 995). A significant reduction in cocaine use over an 18-month
      period from 84 to 48% was found for a sample of clients (n = 266). Overall
      retention in programme was high and also the prevalence of factors associated
      with cocaine use such as criminality, prostitution, and contact with drug scene
      decreased. CONCLUSIONS: The results suggest that prescribed heroin maintenance
      provides a treatment context that may help reduce consumption of other illicit
      drugs such as cocaine.

PMID- 12050927
TI  - [High addiction risk in Switzerland: which direction toward a new narcotic law?].

PMID- 12050928
TI  - Development of a monitoring system for heroin-assisted substitution treatment in
      Switzerland.
AB  - OBJECTIVES: Switzerland introduced heroin-assisted treatment as a routine
      treatment for drug addicts. As a result the evaluation instruments were changed
      from a detailed scientific project to a routine monitoring system. The process
      for developing this monitoring system is described. METHODS: The questionnaires
      and assessment instruments were restyled with staff of the treatment agencies.
      Indicators measuring quality of treatment and measures from the future national
      statistic on the addiction support system were integrated into admission, course
      and discharge questionnaires. Currently a system for feedback to treatment
      agencies is being developed. RESULTS: All 21 treatment agencies are participating
      in the monitoring. Assessment quality is high. CONCLUSIONS: The described
      monitoring should provide continuous delivery of basic relevant data on patients.

PMID- 12050929
TI  - Prescription of hypnotics and tranquilisers at the Geneva prison's outpatient
      service in comparison to an urban outpatient medical service.
AB  - OBJECTIVES: Examine whether an overconsumption of tranquillizers exists in prison
      and discuss possible reasons. METHODS: Comparative study during three weeks at
      Geneva: prison outpatient service and Medical Policlinic (MP) of the University
      Hospital. RESULTS: When comparing the 113 (prison) and 151 (MP) male patients
      younger than 39 years, we found important differences concerning the quality and
      quantity of prescriptions of psychoactive drugs: ten times more prison patients
      than patients from the MP were treated with benzodiazepines (BZD). The
      differences persisted even when considering only prisoners who were not known to
      be street drug, alcohol or long time BZD consumers. CONCLUSIONS: The differences
      cannot be explained by the high percentage of drug addicts in prison. Our results
      suggest the importance of factors related to the prison environment.

PMID- 12050930
TI  - Is gender still a non-field?

PMID- 12050931
TI  - [Psychosocial characteristics, methadone dose and heroin use in ambulatory
      methadone treatment: a matched-pair design].

PMID- 12050932
TI  - Global monitoring of average volume of alcohol consumption.
AB  - OBJECTIVES: To estimate the prevalence of different categories of average volume
      of alcohol consumption for World Health Organization (WHO) regions. To check how
      the monitored indicator of average volume relates to prevalence of alcohol
      dependence. To discuss conclusions for establishing a global monitoring system.
      METHODS: Prevalence of different categories of average volume of alcohol
      consumption was estimated by a triangulation of survey results, production, and
      sales figures. The relation between average volume of consumption and prevalence
      of alcohol dependence was analysed by regression techniques. RESULTS: Alcohol
      consumption varies widely by sex, age, and region. It can predict prevalence of
      dependence with about 74% of the variation of the latter explained. CONCLUSIONS:
      With current data, global monitoring of alcohol is possible. However, more and
      better surveys are necessary for the future. They should include patterns of
      drinking to improve prediction of other health outcomes like coronary heart
      disease (CHD) and accidents.

PMID- 12050933
TI  - Constructing vital statistics: Thomas Rowe Edmonds and William Farr, 1835-1845.
AB  - This paper describes the role of these two English statisticians in establishing
      mortality measurements as means of assessing the health of human populations. Key
      to their innovations was the uses for the law of mortality Edmonds claimed to
      have discovered in 1832. In reality he had merely rediscovered a relationship
      between aging and mortality first described mathematically by Benjamin Gompertz a
      decade earlier. During the 1830s Edmonds attempted to interest the medical
      profession in his discovery and to suggest how his discovery could be used to
      assess health of large communities and to study case fatality and therapy. Using
      the rich data of the General Register Office William Farr would develop Edmonds's
      suggestions to produce some of the most sophisticated uses of vital statistics in
      the 19th century. In understanding the motivation of these two statisticians, it
      is essential to recognise their reform sympathies in an age deeply troubled by
      the human costs of rapid industrialisation and urbanisation. The two set out to
      reform both their professions and society.

PMID- 12050935
TI  - ["I tried to be as defiant as possible". Case histories with autobiographical
      diaries: relationship with the custodial parent during childhood as recalled by
      young adults].
AB  - The predominant structural orientation of divorce research which either ignores
      or under represents to a great extent the child's perspective and his/her agency
      is criticized. As a consequence of these methodological shortcomings not only the
      production of scientific knowledge but also professional practice working with
      children from divorced families might be negatively affected--especially the
      regulation of custody and visiting issues. Therefore, the aim of this article is
      to give children a voice in describing their own experiences of visits and
      relationships with the non-residential father or mother during childhood and
      adolescence (sometimes until adulthood). By presenting numerous detailed
      autobiographical narratives from children of divorced parents, the study revealed
      a great diversity of visiting patterns as well as different relationship
      qualities ranging from loving to negative. In addition, visiting patterns and
      relationship qualities were not always static but were dynamic and changed over
      time, whereby the child's personality and agency contributed to this diversity
      and these processes. Finally, methodological recommendations are offered and it
      is suggested that the child's perspective and agency should be included in
      research about children of divorce.

PMID- 12050934
TI  - [Diagnosis related groups (DRG) in child and adolescent psychiatry: results of a
      prospective pilot study].
AB  - Germany faces one of the biggest 'revolutions' in the health care system. As
      decided by the government in cooperation with medical boards and insurances,
      beginning with January 1st, 2003 all inpatient treatments will be paid on the
      basis of adapted Australian-Refined Diagnosis Related Groups. To date, hospitals
      are requested to obtain prospective databases in order to cluster homogeneous
      diagnostic groups and calculate realistic treatment-costs. Both psychiatry and
      child and adolescent psychiatry are so far excluded from the introduction of
      DRGs. However, most experts predict extensive shifts of patients into psychiatry
      (i.e. with comorbid internal diseases) under the pressure of short treatments in
      all non-psychiatric disciplines. Therefore, changes in the payment of psychiatric
      treatments are inevitably. As part of the DRG pilot-study, we created a catalogue
      adapted to child and adolescent psychiatry, which was used for 102 consecutively
      treated inpatients of a child and adolescent hospital. A total of 17.019
      prospectively assessed procedures were obtained. Under clinical aspects, 11
      categories of 'typical' disorders were analysed. Worst predictability of
      treatment costs was found for obsessive-compulsive disorders, personality
      disorders, and eating disorders. Comorbidity and complexity of the disorder was
      not related to the length of hospital treatment. Implications on future payment
      systems in child and adolescent psychiatry are discussed.

PMID- 12050936
TI  - [Changes in test norms of spelling achievement and nonverbal intelligence].
AB  - The norms of the spelling test R-T Form C "Moselfahrt" (Althoff et al. 1974) from
      the year 1968 and of the nonverbal intelligence test CFT 20 (form A/part 1) from
      the year 1977 (Weiss 1987) are evaluated for their actual validity. In 1995, both
      original tests were being administered to an epidemiological sample (N = 592) of
      adolescents and young adults in the age of 16 to 30 years having passed at least
      their obligatory amount of school years. These results are being compared to
      those of the original norm samples. Using the norms for the CFT 20 from 1977
      adolescents and young adults achieve in the year 1995 a mean IQ of 110.8 points,
      equaling a yearly IQ-gain of 0.6 IQ-points. This exceeds the expected gain of
      0.33 IQ-points annually according to the literature and indicates a distinct
      change of norms. There were no significant gender differences found. The
      distribution of mistakes in the spelling test R-T "Moselfahrt" compared to the
      original norm sample from 1968 changes considerably as well and requires revised
      test norms. With an increase from 9-11 mistakes (depending on the age norm) to
      19.8 mistakes the mean amount of mistakes is almost being doubled. Extremely high
      numbers of mistakes occurred more frequent and could not be differentiated
      according to the old norms. Using the original norms from 1968 in the year of
      1995 12.4% of the sample achieve with a T-score of 20 the lower limit of the
      measured value scale and the overall mean has decreased by 1.2 standard
      deviations to T-score = 38.48% of the sample reach a result that equates
      percentage 10 or less which is interpreted as insufficient school mark. Women's
      mean spelling achievement is significantly better than men's. Causes and
      implications of this scissors-like development of deteriorated spelling
      achievement and increased nonverbal intelligence are being discussed. Tables
      containing the new standardization scores are included in the appendix.

PMID- 12050937
TI  - [Maturation, separation and social integration. Some developmental psychology
      aspects of childhood sports].
AB  - The unfolding of motorical and social experiences with one's own body is a core
      element of ego-development and identity in childhood and adolescence. This paper
      describes essential elements of this process in different age stages. Especially
      in adolescence, the maturational and separational development are determined by
      the complex interaction between integration into the peer group and separation
      from adults, between search for appreciation and oppositional tendencies. On the
      one hand sport plays an important role for many adolescents during this process.
      On the other hand adolescent conflicts have a great impact on practising sport.
      These considerations are illustrated by two case vignettes.

PMID- 12050938
TI  - [Medical doctors in Italy: a situation analysis].
AB  - In 1999, there are 336,000 medical doctors in Italy, as compared to 86,000 in
      1964. The present-day ratio is 583 physicians per 100,000 population. Italy has
      probably the highest level of medical staffing in the world. The medical school
      intake has been controlled since the early 90's and the annual number of new
      graduates has recently decreased. However, the number of active doctors has not
      yet been stabilized. After the recent statistics, nearly 39,000 medical doctors
      cannot find a job in the various medical fields, i.e. more than 11% of the
      profession. Furthermore, a great number of doctors have not a full-time job.
      Surprisingly, the physician/population ratio is lower in the northern provinces
      where the per capita GDP is much higher than in the South. The feature evidences
      the importance of non-economic factors in shaping the geographic distribution of
      health workforce.

PMID- 12050939
TI  - [Transitional health system and health status in Hungary].
AB  - The road towards political freedom has been painful to the Hungarian population.
      After 1989, the per capita GDP has sharply decreased, and the 1989 level has been
      reached again only a decade later. During the period, a great number of reforms
      have been launched in the health field: privatisation, adoption of a Bismarckian
      like model, decentralization, performance-search measures... One cannot say
      however that these reforms have been successful. Low priority for health, vastage
      of the scarce resources allocated to the health care system, conflicts for power
      between the groups and institutions ... have seriously weakened the performance
      of all the system. Simultaneously, the financial burden charged to the patients
      has increased and the unhealthy lifestyle of the population has not decreased. In
      its 2000 Report on the world health, WHO has noted that Hungary is ranked 36th
      for per capita GDP, 59th for per capita health expenditures but 105th for the
      performance of its health care system.

PMID- 12050940
TI  - [Consistency of data on medical manpower: the French experience ].
AB  - Various sources provide statistics on medical doctors in France: (i) for
      deontologic control purpose, physicians have to register with the Medical
      Council: (ii) moreover, they have to declare their diploma to the local health
      administration; (iii) the reimbursements made by the Sickness Insurance Fund make
      it possible to obtain statistics on doctors in private practice. Until recently,
      the sources in (i) and (ii) provided data evidencing large gaps, although
      theoretically they covered all active medical doctors in France. From 1998
      onwards, the statistical office of the Ministry of Health undertook a project
      aimed at estimating the accurate number of active physicians by region, specialty
      and place of work (hospital or ambulatory care). The project was based, inter
      alia, on the annual survey of employment conducted by the National Statistical
      Office. The results were reasonably consistent. The article describes the various
      steps of the endeavour and the difficulties encountered.

PMID- 12050941
TI  - [Health resources allocation in Canada provinces: the role of indicators of
      health needs].
AB  - In an attempt to limit their health care expenditures Canadian provinces have
      strengthened the necessity to allocate health care resources according to their
      population needs. The difficulties and limitations of the needs-based approach
      are explored. First, indicators of population needs for health care were
      introduced into a formula of resource allocation for hospital-based services in
      England in the late 1970. Secondly, there are broad similarities between both the
      philosophy and resource allocation strategies of Canada and Britain. Thirdly, the
      main definition of a needs indicator is to measure the level of equity- or
      inequity-in the distribution of health care resources between regions. Fourthly,
      a needs indicator, as least as developed by the Canadian provinces, concerns
      general and specialized services that should be found in each of their regions.
      Fifthly, a needs indicator constitutes a tool for the calculation of a capitation
      rate. Finally, future research should focus on parameters which are not an
      integral part of the allocation method, but which have a strong impact, in the
      attainment of regional equity such as administrative decisions that are taken
      when budgets are to be allocated or reduced between regions.

PMID- 12050942
TI  - [Managed care and the under-privileged in the United States].
AB  - It has been said that "vulnerable populations" (elderly people, chronic
      patients,...) were largely affected by the Managed Care. The following article
      shed a light on the quality of care delivered to Medicaid patients under Managed
      Care. After a short description of the US Managed care experience, the
      specificities and difficulties (quality, adverse selection, non-compliance...) of
      Medicaid patients under capitation plans will be described.

PMID- 12050943
TI  - [Attitude to and marketing of cerivastatin].

PMID- 12050944
TI  - [Androgen substitution in men from the urologic point of view].
AB  - Androgen substitution has been intensively debated due to major concerns with
      respect to unknown interactions with prostate cancer initiation and progression.
      Certainly, androgen substitution should be considered in men with symptomatic
      hypogonadism (< 1% of men) in whom prostate cancer has been excluded. Serum PSA
      values should not exceed the currently employed age specific reference values (40
      50 years: 2.5 ng/ml, 50-60 years: 3.5 ng/ml, 60-70 years: 4.5 ng/ml and over 70
      years: 6.5 ng/ml). A family history of prostate cancer and/or prostatic
      intraepithelial neoplasia (PIN) should be considered as relative
      contraindications. If androgen substitution is to be initiated, serum PSA should
      be monitored at 3 month intervals including digital rectal examinations (DRE). In
      case of abnormal results (PSA and/or DRE) substitution therapy should be
      terminated and random prostate biopsies performed. In addition, major issues
      regarding the optimal substitution pathway (transdermal versus intramuscular
      versus implants versus oral) remain unclarified and require further
      investigation. Furthermore, little is known about the precise type and dosage of
      androgens to be substituted. Lastly, only 10%-18% of men with hypogonadism are
      symptomatic, reducing the number of patients in whom substitution therapy may be
      an option significantly. Although substitution therapy is valuable in selected
      men, unclear issues related to prostate cancer initiation and progression,
      timing, type and dosage of androgen substitution raise major concerns and need
      further investigation. Meanwhile patients need to be counselled and advantages
      balanced against disadvantages, side effects and potential risks.

PMID- 12050945
TI  - [Indications and results of endoscopic examinations in intensive care units].
AB  - The aim of the study was to analyze retrospectively all endoscopies performed on
      3 intensive care units in a tertiary referral center with more than thousand beds
      during a period of ten years. The study evaluates all endoscopies with regard to
      indication and findings. In the years 1989-1998 a total of 326 endoscopic
      examinations was performed, most of them were done as an upper gastrointestinal
      endoscopy (88%). In more than 87% the indication was a suspected gastrointestinal
      bleeding. The most frequent findings consisted in ulcers of the stomach or
      duodenum and esophageal varices, then followed by Mallory-Weiss-lesions,
      esophagitis and erosive gastritis. The etiology of gastrointestinal bleeding was
      similar to that of non intensive care patients. Specific causes of bleeding such
      as esophagitis caused by nasogastric tubes were only found in 3% of all
      bleedings. The numbers of endoscopies on the 3 intensive care units were
      increasing during the ten year period, however the numbers of the patients
      treated on the intensive care units were also increasing, but the increase of
      endoscopies was not always parallel to the rising number of intensive care
      patients.

PMID- 12050946
TI  - Long-term observation study of Austrian patients with rheumatoid arthritis.
AB  - We examined retrospectively in a long-term observation study the outcome of
      patients with RA in Austria. Eighty-one inpatients with definite rheumatoid
      arthritis (RA) completed a standardized clinical and laboratory examination 3-8
      times between 1978 and 1999. The course of the disease was assessed by
      determining the disease activity score (DAS), 28-joint count (28 JC), 30 swollen
      joint count (30 SJC), proximal interphalangeal joint score (PIP), Ritchie index,
      Stoke index, Steinbrocker stage, and Larsen score. In a mean duration of follow
      up of 10 years, we observed a statistically significant improvement in PIP,
      Ritchie index, Stoke index, and DAS. Steinbrocker stage and Larsen score
      increased significantly. A high percentage of the patients did not receive any
      disease-modifying antirheumatic drug (DMARD) within the first 2 years of disease.
      Of all drugs used, methotrexate (MTX) was continued longer than other DMARDs. The
      most frequent extra-articular manifestation was sicca syndrome. In our long-term
      follow-up, a change in treatment from the onset of the disease in the 1980s to a
      more aggressive treatment within the last decade could be observed. However, with
      respect to the significant increase in Steinbrocker stage and Larsen score as
      well, an early aggressive therapy is required. With respect to the association of
      ANA and extra-articular manifestations, elevated ANA should give rise to an exact
      organ screening. For the development of predictive factors for the outcome in
      patients with RA, it would be helpful to refer patients at risk to specialist
      care as soon as possible.

PMID- 12050947
TI  - Erythrocyte mean cellular volume and its relation to serum homocysteine, vitamin
      B12 and folate.
AB  - Cobalamin (B12) and folate deficiency is related to both increased erythrocyte
      mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values.
      Furthermore, there are indications that B12 and folate serum values do not
      represent the tissue status of the two vitamins exactly. Therefore, a direct
      relationship between MCV and tHcy, if demonstrated, could support the hypothesis
      that tHcy is a better indicator for the cited vitamin status than the serum
      levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum
      B12, folate and tHcy values in 200 hospitalized patients. There was a significant
      correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P <
      0.001), but not with serum B12 and folate. Stepwise multiple linear regression
      with MCV as dependent and GGT, B12, folate and tHcy as independent variables,
      respectively, revealed significant associations of MCV with GGT (B = 2.18, 95% CI
      0.95-3.42, P = 0.001) and tHcy (B = 3.33, 95% CI 1.26-5.39, P = 0.002). By
      removing tHcy from this model, serum B12 became a significant predictor of MCV (B
      = -1.70, 95% CI -3.25 to -0.15, P = 0.032). Serum folate was not significantly
      associated with MCV in multivariate analysis. In conclusion, the present study
      confirms indications that serum B12 and folate values lack clinical sensitivity
      and specificity in diagnosing vitamin deficiency states by showing MCV was better
      associated to tHcy, than to B12 or folate serum levels. This observation
      demonstrates that tHcy may be useful in diagnosing patients with B12 and/or
      folate deficiency.

PMID- 12050948
TI  - Interleukin-2 activation of haematopoietic stem cells.
AB  - BACKGROUND: Recent findings concerning the role of immunity in the eradication of
      residual malignant disease after autologous haematopoietic stem cell
      transplantation have led to extensive studies of T-cell and natural killer (NK)
      mediated anti-tumour effects. Interleukin 2 (IL-2) activation of autologous bone
      marrow (BM) or peripheral blood stem cells (PBSC) before transplantation is one
      of the methods of adoptive cell therapy. METHODS: Autologous BM of patients with
      chronic myelogenous leukaemia (n = 11) and PBSC of patients with multiple myeloma
      (n = 14) were activated by IL-2 in laboratory conditions with the aim of
      evaluating the feasibility of this method, the activation of T and NK cells,
      recovery of active progenitor cells, microbial contamination, and reduction of
      malignant cell content. RESULTS: Samples of BM (mean 2.6 x 10(6) cells) and PBSC
      (mean 10.3 x 10(6) cells) were cultured in complete culture medium with IL-2
      (6000 Ul/ml) for 24 h. The recovery of CD34+ cells and CFU-GM was 82.5% and
      51.5%, respectively, for BM, and 85% and 86%, respectively, for PBSC (mean
      values). No purging effect was detected by flow cytometry and a small decline in
      malignant cell contamination was observed by quantitative PCR in BM samples. No
      microbial contamination occurred during the sample processing. CONCLUSIONS: The
      described in vitro activation of BM and peripheral blood stem cells using IL-2
      was evaluated as a safe and reliable method suitable for clinical application.

PMID- 12050949
TI  - [Value of a structured report for the interpretation of parathyroid scintigraphy
      in primary essential hyperthyroidism].
AB  - The aim of the study was to evaluate whether a four-stage report scheme increases
      the diagnostic accuracy of dual phase Tc-99 m sestamibi scintigraphy (MIBI
      scintigraphy) in patients with primary hyperparathyroidism (pHPT). We analysed
      the scans of 35 patients with primary hyperparathyroidism referred for Tc-99 m
      sestamibi scintigraphy and compared them with the sonographic and surgical
      findings. All scans were interpreted following a four-stage report scheme: Group
      A--typical scintigraphic findings of a single gland disease, group B--scan
      consistent with single gland disease, group C--multiple gland disease, group D-
      non diagnostic scan. Twenty-three scans were ranked in group A. In all these
      patients, scintigraphy diagnosed both the side and the localization of the
      adenoma correctly. Sonography made the correct diagnosis in 21/23 individuals and
      showed false-positive results in 2/23 cases. Group B included 10 scans. In 7/10
      individuals, both the side and the localization of the adenoma were diagnosed
      correctly, whereas in 2/10 patients only the side was diagnosed. The scan of a
      single patient with hyperplasia of all 4 parathyroid glands was falsely
      interpreted as "consistent with a left caudal single gland disease". Sonography
      made the correct diagnosis in 8/10 cases, two individuals were diagnosed as false
      positive and false negative, respectively. No scan was interpreted as multiple
      gland disease (group C) and two scans were non diagnostic (group D). Both
      patients of the last group were correctly diagnosed by sonography. These findings
      suggest that in case of typical scintigraphic findings of single gland disease,
      scintigraphy but not sonography should be the primary localization technique for
      minimally invasive parathyroidectomy.

PMID- 12050950
TI  - [Efficiency and safety of ACE-inhibiting imidapril in patients with essential
      hypertension].
AB  - In a survey including 2224 patients with essential hypertension we investigated
      efficacy and tolerability of the new ACE-inhibitor Imidapril. Mean blood pressure
      at baseline was 172 +/- 19/98 +/- 10 mmHg. Treatment with Imidapril 5-20 mg once
      daily caused a decrease in BP by 21 +/- 17/11 +/- 10 mmHg (p < 0.01/0.01).
      Systolic BP was reduced by > 15 mmHg in 71% diastolic BP by > 10 mmHg in 64% of
      patients. 29% of patients achieved the treatment goal of a blood pressure < or =
      140/90 within an average of 26 days. Imidapril decreased pulse-pressure (one of
      the most important risk markers in hypertension) by 18% (74 +/- 17 to 61 +/- 11
      mmHg, p < 0.01). ACE-inhibitor related adverse effects (cough, vertigo, headache,
      pruritus, tachycardia, orthostatic dysregulation or nausea) were observed in 38
      patients (< 2%). Efficacy of treatment was graded by the physician in charge of
      the patient care by means of a questionnaire. Gradings were excellent or good in
      96% of patients, moderate in 3% and poor in < 1%. In summary, the effects of
      Imidapril on blood pressure were comparable to those of other ACE-inhibitors.
      However, the frequency of adverse effects was low and similar to that of
      angiotensin-II-antagonists.

PMID- 12050951
TI  - [Changes in the systemic immunologic response in association with endometriosis
      using an animal model].
AB  - INTRODUCTION: Endometriosis constitutes the growth of endometrial tissue in a
      place other than the uterine cavity. Its etiopathogenesis is unknown, although
      there is some evidence associating it with the decrease of cytotoxic activity in
      the immunological system. OBJECTIVE: Evaluating the relationship between the
      development of ectopic endometrial tissue and the immunological status, and
      enumerating lymphocyte subpopulations and cytokine synthesis in T lymphocytes,
      using a murine endometriosis model. METHODOLOGY: Spleen lymphocytes isolated from
      two study groups of 10 female mice of the Balb/c strain that had been submitted
      to the surgical implantation of autologous endometrial tissue in the peritoneal
      cavity, and sacrificed after 5 (group I) and 8 (group II) weeks, were incubated-
      or not--with PMA/lonomicine. Lymphocyte T numbers and their cytokine production
      were determined by flow cytometry. RESULTS: A lower dispersion of the ectopic
      tissue growth value was observed in group II (24% vs. 42%). A smaller population
      of cytotoxic T lymphocytes and a greater IL-4 production in the stimulated cells
      of the study group (p < 0.05) were observed, as compared to the control group.
      CONCLUSIONS: The presence of endometrial tissue in the uterine cavity decreases
      the amount of cytotoxic T lymphocytes and increases IL-4 production in total T
      lymphocytes, suggesting a modulation of the systemic immunological response to TH
      2.

PMID- 12050952
TI  - [Changes in mitochondrial membrane potentials and its exponential relation with
      phosphatidylserine translocation in the plasma membrane as markers in the initial
      events of apoptosis: evaluation in different spermatic fractions].
AB  - OBJECTIVE: To determine the integrity of the plasmatic membrane through
      phosphatidylserine (PS) translocation in two spermatic fractions and their
      correlation with the spermatic mitochondrial membrane potential. MATERIAL AND
      METHODS: The analysis of both spermatic fractions was carried out through a
      discontinuous gradient separation with Percoli, in order to obtain two samples
      with high and low mobility (90-40%). Twelve patients were recruited for the
      initial evaluation of seminal parameters. Mitochondrial membrane integrity was
      determined using a second antibody (Mitosensor), and was analyzed by fluorescence
      microscopy, evaluating an average of 200 cells. A 450-490 nm excitation filter
      was used for this analysis. Cytoplasmatic assessment was carried out by anexine V
      bonding to PS, in order to determine the initial events of cellular death. Non
      parameter tests were used in order to determine the differences between
      mitochondrial potentials and plasmatic membrane processes. Linear correlation
      tests were used for the anexine V and Mitosensor ratios. RESULTS: Due to the
      study's design, some differences were observed regarding the displacement
      parameters and the presence of apoptosis, both, in the plasmatic membrane and in
      mitochondrial membrane potentials. A positive correlation between both,
      mitochondrial and cytoplasmic membrane functions was also found. CONCLUSIONS:
      This is the first study performing a comparative analysis between mitochondrial
      membrane function and cytoplasmatic PS expression as early cellular death
      markers. The male infertility population is probably associated with an increase
      in this kind of apoptosis processes.

PMID- 12050953
TI  - [Biochemical and ultrastructural characterization of the effect of interleukin 1
      beta as mediator of the degradation of connective tissue in human chorioamniotic
      membranes in culture].
AB  - OBJECTIVE: To characterize the effect of IL-1 beta, on connective tissue
      metabolism in a human chorioamniotic membrane tissue culture (CAM). TYPE OF
      STUDY: Experimental, in an in vitro model. MATERIAL AND METHODS: CAM explants
      obtained from cesarean sections were cultured. The presence of local infection
      was excluded by microbiological methods. An XTT viability essay of the explants
      was carried out. Explants were stimulated with different doses of IL-1 beta
      within a 0-10 ng/mL range. After the stimulation, protein content was measured,
      MMP-9 production was determined by zymography, and each explant was divided in
      two parts: one was used for collagen measurement and the other analyzed by
      electronic microscopy. RESULTS: CAMs kept adequate viability and functionality.
      IL-1 beta stimulation produced an increase in the amount of MMP-9 expressed, as
      determined by the zymography method with a maximum effect 36 hours after
      stimulation. Collagen content decreased in a progressive manner after IL-1 beta
      stimulation and reached its minimum after 36 hours. The characteristic pattern of
      collagen fibers gradually lost its organization, and could not be observed any
      more after 36 hours. CONCLUSIONS: The information presented here allows us to
      conclude that IL-1 beta is capable of inducing an enzymatic expression affecting
      connective tissue, thus confirming its participation in membrane degradation
      processes under inflammatory conditions.

PMID- 12050954
TI  - [Ovum-embryo competitiveness determined by the quantification of perifollicular
      indices in Doppler vascular micro-architecture].
AB  - OBJECTIVE: To obtain the linear correlation between Doppler flowmetry rates and
      follicular development and the observed embryo growth in ovarian hyperstimulation
      cycles in the IVFTE/ICSI results. MATERIAL AND METHODS: A prospective and
      observational study including 29 patients was carried out. The ovarian reserve
      was determined--by the ovaries morphometric conditions--as well as basal FSH.
      These were correlated with pulsatility rates (PR), resistance rates (RR), and the
      systole/diastole ratio (S/D) and the maximum flow rate (TAmax), using a USG pulse
      colour Doppler. All these were correlated to embryo development. Covariance,
      regression lines and confidence intervals analyses were performed for its
      statistical determination. RESULTS: A correlation between RR and the formation of
      mature follicles was observed (p = 0.05), and, at the same time, a negative
      relationship between FSH and ovarian volume was found. CONCLUSIONS: A series of
      markers of ovarian reserve have been described, however, none of these is a
      specific marker when ovum quality is expressed through the administration of
      ovulation inducers. Considering the data obtained in our study, we can say that
      Doppler flowmetry rates can indicate follicular expression and the resulting ovum
      and embryo development.

PMID- 12050956
TI  - [Pelvic surgery as a predictive marker of the follicular response to ovulation
      inducers].
AB  - OBJECTIVE: Comparing the follicular response in a group of patients with previous
      pelvic surgery submitted to in vitro fertilization. MATERIAL AND METHODS:
      Patients who were going to be submitted to controlled ovarian stimulation and in
      vitro fertilization were included. Two groups were formed: one with those
      patients who had had a previous pelvic operation and the other with those
      patients who had not. The characteristics which were analyzed included: age,
      weight, body mass index, FSH, LH and estradiol levels, as well as total ova
      numbers, grade of embryonic maturity, and number of transferred embryos. RESULTS:
      Ninety nine patients were studied: 46 had been submitted to pelvic surgery and 53
      had not. Due to the design of the study there were no differences regarding age,
      weight, size and body mass index; the evaluation of the ovarian reserve was
      similar in both groups. However, the group of patients previously submitted to
      pelvic surgery presented a lower quantity of total ova (p = 0.004), less mature
      ova (p = 0.008) with a significantly lower pregnancy rate. CONCLUSIONS: Surgical
      procedures, combined with adherence processes, probably have a direct incidence
      on the characteristics of the perifollicular environment which interfere with
      adequate development of the ovum. All these can be observed in a decrease of
      fertilization processes and embryonic development, regardless of the expression
      of the adequate biochemical markers of the ovarian reserve. Our research shows
      that the group under study presents a decrease in follicular response affecting
      the quality of the ovum-embryo expressed in the pregnancy rate.

PMID- 12050955
TI  - [Cervicovaginal infection as a risk factor for premature labor].
AB  - OBJECTIVE: To identify the possible association between cervicovaginal infections
      (CVI) and preterm delivery. DESIGN: Cohorts. REFERENCE FRAME: Instituto Nacional
      de Perinatologia, Hospital Central Militar and Hospital General Regional No. 1,
      IMSS, Culiacan, Sinaloa, Mexico. PATIENTS: Four hundred and sixty eight patients
      attending prenatal control and delivery care. INTERVENTIONS: Fresh smears, Gram
      stain, and cervicovaginal sample culture from samples obtained during the
      following gestational stages: First sample at 16-24 weeks, second sample at 25-32
      weeks, and third sample at 33-42 weeks. The following microorganisms were
      studied: Candida albicans, Gardnerella vaginalis, Ureaplasma urealyticum,
      Streptococcus agalactiae, Mycoplasma hominis, Neisseria gonorrhoeae, Listeria
      monocytogenes, and Chlamydia trachomatis. In case of a positive culture, the
      specific treatment was indicated. MEASUREMENTS: Positive or negative culture for
      each of the studied pathogens, and the presence or absence of a preterm delivery
      for each of the patients included in the study. RESULTS: Three hundred and ninety
      eight were still present at the end of the study, of which 156 had a CVI and 242
      had no CVI. No differences between both groups were observed concerning preterm
      delivery. Significant relative risks were: In the first stage, Ureaplasma
      urealyticum and Mycoplasma hominis with RR = 9.0 (6.81, 11.8); in the second
      stage, Ureaplasma urealyticum with RR = 6.2 (3.30, 11.7) and Escherichia coli
      with RR = 3.4 (1.33, 8.6); in the third stage, Ureaplasma urealyticum with RR =
      9.19 (6.93, 12.1). The logistic regression analysis identified Ureaplasma
      urealyticum during the second stage with OR = 16.6 (2.9, 93.7), statistically
      significant with p = 0.001. The survival analysis showed differences between the
      two groups concerning pregnancy duration (p < 0.001). CONCLUSIONS: There is a
      difference in the duration in pregnancy in patients with CVI and without CVI.
      Ureaplasma urealyticum is consistently associated with preterm delivery.

PMID- 12050957
TI  - Births, marriages, divorces, and deaths: provisional data for September 2001.

PMID- 12050958
TI  - Office and emergency room violence.

PMID- 12050959
TI  - Urologic complications of placenta percreta invading the urinary bladder: a case
      report and review of the literature.
AB  - INTRODUCTION: Placenta percreta invading the urinary bladder may cause
      hemorrhagic shock, hematuria and urologic complications at parturition. This
      retrospective survey of 54 patients reviews maternal characteristics,
      presentations, urologic complications, and management. METHODS: The first
      reported case of placenta percreta with urinary bladder invasion in Hawaii is
      presented. Medline search and literature review identified an additional 53
      patients. A meta-analysis of all 54 cases was performed. RESULTS: Hematuria was
      present initially in 31% (17/54) patients. Of these, 9 of 17 required transfusion
      support. A preoperative diagnosis was established by ultrasound or MRI in 33% of
      patients. Cystoscopy was performed in 12 patients and did not make a preoperative
      diagnosis in any patient. 39 urologic complications included bladder laceration
      26%, urinary fistula 13%, gross hematuria 9%, ureteral transection 6%, and small
      capacity bladder 4%. Partial cystectomy was performed in 44% (24/54). Three
      maternal deaths and 14 fetal deaths occurred. Only 1 patient subsequently had a
      delivery. CONCLUSION: Readily identifiable risk factors by history are important
      to suggest placenta percreta in pregnant patients with gross hematuria.
      Ultrasound and/or MRI can establish a preoperative diagnosis. Cystoscopy did not
      identify any patient preoperatively. Partial cystectomy is commonly required for
      extensive or deep bladder invasion.

PMID- 12050960
TI  - Chylothorax and cirrhosis of the liver: a case report.
AB  - Chylothorax occurring in the setting of a lymphoma or a surgical procedure
      involving the area around the thoracic duct is a well-known phenomenon. Less
      common is the occurrence of chylothorax in conjunction with cirrhosis of the
      liver. Due to the paucity of data, it is uncertain if chylothorax is an
      associated or an independent sign of cirrhosis. The case reports in the
      literature favor the former, as demonstrated in this case of a patient with
      cirrhosis of the liver who developed a chylothorax.

PMID- 12050961
TI  - The phrase: "no ifs, ands, or buts" and cognitive testing. Lessons from an Asian
      American community.
AB  - This study assessed the clinical utility of repeating the phrase "No ifs, ands,
      or buts" for cognitive testing in Hawaii. 242 subjects were screened; 25 (10%)
      had cognitive impairment. 68% of all subjects were unable to say the phrase "No
      ifs, ands, or buts" (83% of cognitively impaired and 67% of cognitively intact, p
      = 0.122). Specificity for cognitive impairment was poor.

PMID- 12050962
TI  - Imi Ho'ola Post-baccalaureate Program: one solution to the crisis of inadequate
      representation of minorities in medicine.

PMID- 12050963
TI  - Carotenoids and human health.

PMID- 12050964
TI  - Lifestyle-related, non-communicable diseases--the world picture.

PMID- 12050965
TI  - Clinical aspects of obesity and diabetes mellitus.
AB  - Obesity is a major risk factor for Type 2 diabetes mellitus in all populations
      worldwide. Measuring obesity remains a controversial issue with the validity of
      some measures constantly being reviewed. Recent data have shown the usefulness of
      simple clinical measures like waist-circumference in predicting risk and
      monitoring intervention. While we lament the burden of obesity, it provides an
      opportunity for intervention, which could go a long way in ameliorating the
      burden of diabetes mellitus.

PMID- 12050966
TI  - Community aspects of obesity and diabetes mellitus.

PMID- 12050967
TI  - Success for children with type 2 diabetes mellitus.

PMID- 12050968
TI  - Promoting healthy lifestyles through the strategy of healthy municipalities and
      communities.

PMID- 12050969
TI  - Healthy lifestyles through the health-promoting schools initiative.

PMID- 12050970
TI  - Obesity prevention in Brazil.

PMID- 12050971
TI  - Latin American experiences in the prevention of obesity.

PMID- 12050972
TI  - Surgical alternatives for the morbid obese.

PMID- 12050973
TI  - Caribbean lifestyle intervention (CARLI).

PMID- 12050974
TI  - The effects of sedentarism and physical activity on children's health.

PMID- 12050975
TI  - The "Agita Sao Paulo" experience in promoting physical activity.

PMID- 12050976
TI  - Obesity and diabetes mellitus--how are they linked?
AB  - There is a large body of evidence which indicates that elevated plasma levels of
      FFA are a major cause of insulin resistance in skeletal muscle and liver.
      Normalizing plasma FFA levels is, therefore, proposed as a novel approach to
      reduce insulin resistance, the risk of Type 2 diabetes mellitus and
      atherosclerotic vascular disease.

PMID- 12050977
TI  - The role of communication and the prevention of obesity.

PMID- 12050978
TI  - A new partnership for reproductive health in Zambia.

PMID- 12050979
TI  - Terrorism and public health: the little known equation.

PMID- 12050980
TI  - Alcohol and youth: time for effective action.

PMID- 12050981
TI  - Alcohol's role in the deaths of BC children and youth.
AB  - OBJECTIVE: To determine the prevalence and context of alcohol use in the deaths
      of children and youth reviewed by the BC Children's Commission. METHODS: In 489
      case reviews of BC children and youth, we examined the role that alcohol may have
      had at the time of death or whether there was a history of alcohol use either by
      the deceased child or another person in the child's life. RESULTS: Alcohol is
      most prevalent in the lives of 15-18 year olds. It is present at the time of
      death in two fifths of Motor Vehicle Incidents (MVI) and one third of suicides
      and drownings. INTERPRETATION: Alcohol has a profound presence in the lives and
      deaths of children reviewed by the Children's Commission. Enhancing deterrence
      laws and alcohol control policies, and increasing public awareness are warranted.

PMID- 12050982
TI  - The early effects of Ontario's Administrative Driver's Licence Suspension law on
      driver fatalities with a BAC > 80 mg%.
AB  - BACKGROUND: On November 29, 1996, Ontario introduced an Administrative Driver's
      Licence Suspension (ADLS) law, which required that anyone charged with driving
      with a blood alcohol concentration (BAC) over the legal limit of 80 mg% or
      failing to provide a breath sample would have their licence suspended for a
      period of 90 days at the time the charge was laid. This study evaluates the early
      effects of Ontario's ADLS law on alcohol-involved driver fatalities. METHODS:
      Interrupted time series analysis with ARIMA modelling was applied to the monthly
      proportion of drivers killed in Ontario with a BAC over 80 mg% for the period
      Jan. 1, 1988 to Dec. 31, 1997. RESULTS: A significant intervention effect was
      found, with ADLS being associated with an estimated reduction of 17.3% in the
      proportion of fatally injured drivers who were over the legal limit. CONCLUSION:
      These data provide an early indication that the law resulted in some success in
      reducing alcohol-related driver fatalities.

PMID- 12050983
TI  - Community capacity building: a parallel track for health promotion programs.

PMID- 12050984
TI  - A review of theory and health promotion strategies for new immigrant women.
AB  - BACKGROUND: There has been little empirical research on the best ways to
      influence women's health behaviour, particularly among women who are recent
      immigrants to Canada. METHODS: This paper presents information from a literature
      review conducted for the Ontario Women's Health Council on effective theoretical
      models and health promotion strategies for women. FINDINGS: Health promotion
      activities for all women should address theoretical variables as well as the
      broader determinants of women's health. New immigrant women represent a diverse
      group who often face multiple cultural, linguistic and systemic barriers to
      adopting and maintaining healthy behaviour. INTERPRETATION: Many theoretical
      constructs of potential importance to recent immigrant women have not been
      adequately researched. More research is also needed on the relevancy and the
      applicability of commonly used health promotion approaches for this group.

PMID- 12050985
TI  - Country of birth and language spoken at home in relation to illicit substance
      use.
AB  - BACKGROUND: This study examines the association between country of birth,
      language spoken at home, and lifetime illicit substance use in a Canadian
      national sample. METHOD: Secondary analysis of data was conducted using a sample
      of 8,656 persons who were between 15 and 54 years of age in 1994 and who
      participated in Canada's Alcohol and Other Drugs Survey. RESULTS: Rates of
      substance use differed among the four groups (42.6% for Canadian-born who spoke
      official languages, 33.8% for Canadian-born who spoke non-official languages,
      35.2% for foreign-born who spoke official languages, and 11.1% for foreign-born
      who spoke non-official languages). The rate differences persisted after
      adjustment for sociodemographic factors, religiousness, friends' use of
      substances, and participation in social activities. INTERPRETATION: More in-depth
      studies that include culture-specific information are required to explain the
      rate differences. In addition, alternative preventive strategies may be required
      to reduce substance use among foreign-born persons.

PMID- 12050986
TI  - Predictors of adolescent self-rated health. Analysis of the National Population
      Health Survey.
AB  - OBJECTIVE: To examine what factors predict adolescents' concepts of their health.
      METHODS: The study, based on the longitudinal National Population Health Survey,
      included 1,493 adolescents who were 12-19 at the time of interview. Sex, age,
      grade, family structure, income, disability, chronic health problems, social
      supports, social involvement, school/work involvement, smoking, alcohol bingeing,
      physical activities, Body Mass Index (BMI) and psychological health status
      variables were examined. Using ordinal multivariate regression, self-rated health
      was regressed on all predictors, which were entered in blocks hierarchically.
      RESULTS: The analyses revealed that adolescent perceptions of health are framed
      not only by their physical health status, but also by personal, socio
      environmental, behavioural and psychological factors. Specifically, health
      problems, disability, age, female status, lower income, smoking, and higher BMI
      were associated with lower self-rated health. CONCLUSIONS: This study suggests
      that adolescent appraisals of their health are shaped by their overall sense of
      functioning, which includes both physical health and non-physical health
      dimensions.

PMID- 12050987
TI  - [Attitudes and subjective norms of Quebecian adolescent mothers towards
      breastfeeding].
AB  - OBJECTIVES: To describe the attitudes and subjective norms of female adolescents
      toward breastfeeding, and to determine whether these are influenced by age,
      education level, mother tongue, place of birth, exposure to breastfeeding and
      intention to breastfeed their children. METHOD: 236 female adolescents, from four
      schools randomly selected among those offering education levels from secondary 1
      to V 4, answered a questionnaire based on the theory of reasoned action. RESULTS:
      Female adolescents showed overall positive attitudes towards breastfeeding, but
      negative subjective norms. Older girls who were breastfed as infants and who
      originated from foreign countries showed the most positive attitudes towards
      breastfeeding. INTERPRETATION: Even though adolescent girls showed overall
      positive attitudes, several were unable to make up their mind. This result could
      be attributed to a lack of knowledge and low exposure to breastfeeding mothers.
      The school system plays an important role in health promotion and should expose
      all students to the art of breastfeeding through its health classes.

PMID- 12050988
TI  - Impact of maternal anemia on the infant's iron status at 9 months of age.
AB  - BACKGROUND: Iron-deficiency anemia during pregnancy is still common in developed
      countries. The aim of this study was to evaluate the influence of maternal anemia
      on the infant's iron status at 9 months of age in Moncton, NB. METHODS: Mothers
      giving birth between April 1998 and February 1999 were selected from medical
      records. A letter was sent to invite them to participate. In total, 75 mothers
      with their infants were examined. RESULTS: The proportion of iron-deficiency
      anemia was higher (p = 0.055) in the group born to anemic compared to non-anemic
      mothers. A positive association between the mother's haemoglobin and haematocrit
      during her 3rd trimester and her infant's haemoglobin and haematocrit was found
      at 9 months of age. These results are not explained by differences in feeding
      practices and socio-economic status between groups. INTERPRETATION: Infants born
      to mildly anemic mothers may be at risk of developing anemia.

PMID- 12050990
TI  - [Behavior and beliefs in amateur open water activities. Study of beliefs and
      attitudes with respect to health risks].
AB  - OBJECTIVE: The objective of this study was to explore beliefs, attitudes and
      suggestions concerning effective interventions to promote the use of sun
      protection, the use of personal flotation devices (PFDs) and the avoidance of
      contact with water unfit for swimming. METHOD: Interviews were conducted with 36
      users and 2 river park activity coordinators on a river in the Greater Montreal
      area. RESULTS: The respondents recognized the existence of a certain number of
      negative beliefs and barriers associated with the adoption of safe behaviours, in
      particular the pointlessness and inconvenience of means of protection against the
      sun and the wearing of PFDs, the negligible effects of polluted water on health
      and the thrill of defying bans. To help change beliefs, attitudes and behaviours,
      the respondents suggested legislative, organizational and individual
      interventions. INTERPRETATION: The data gathered during this study will help to
      determine intervention strategies and to set up programs promoting behavioural
      change among the target population.

PMID- 12050989
TI  - [The habits and perceptions of participants in water and other outdoor activities
      in terms of risk behaviors].
AB  - OBJECTIVE: The objective of this study was to explore the habits and perceptions
      of participants in water and other outdoor activities in terms of health risk
      behaviours. METHOD: A survey was undertaken of 1,200 users of a river in the
      Greater Montreal area. RESULTS: Only about 30% of respondents used some form of
      protection against the sun during every outing. Fewer respondents who used some
      form of motorized water craft wore personal flotation devices (PFDs) compared
      with those who used non-motorized water craft (63% vs. 83%). Almost half of the
      respondents avoided all contact with water unfit for swimming, and this was the
      only instance of behaviour influenced by a perception of serious health risks.
      The data also indicate that men and respondents under 25 years of age are not
      inclined to practise the safe behaviours studied. INTERPRETATION: These results
      suggest that effective interventions must be developed for the population in
      general and for certain sub-groups in particular in order to promote the adoption
      of safe behaviours during water and other outdoor activities.

PMID- 12050991
TI  - Safer and unsafe injection drug use and sex practices among injection drug users
      in Halifax, Nova Scotia. An exploratory look at community and interpersonal
      influences.
AB  - OBJECTIVE: This qualitative study sought to explore the community and
      interpersonal (e.g., peer) influences affecting safer and unsafe injection drug
      use and sexual practices among injection drug users (IDUs) living in and around
      Halifax, Nova Scotia. METHODS: Sixty semi-structured interviews were conducted
      with IDUs, and key themes were identified. Two focus groups were also conducted
      to obtain feedback on the findings. RESULTS: There are key community and peer
      influences on drug use and sex practices. Needle exchange provides community
      access to clean needles, but when the needle exchange is closed, accessibility is
      an issue. Peers at times assist in reducing sharing by providing clean needles to
      friends who are without a needle or cannot access needles because of their
      circumstances (e.g., in prison). Peers also sometimes encourage condom use, but
      in certain contexts (e.g., with an intimate partner) condom use is often not
      supported. INTERPRETATION: Expanded and new prevention strategies--especially
      those utilizing peers--are urgently needed to discourage unsafe practices, and
      encourage safer practices among this population.

PMID- 12050992
TI  - Using willingness to pay to evaluate the implementation of Canada's residential
      radon exposure guideline.
AB  - BACKGROUND: The objective of this investigation was to determine the
      effectiveness of Canada's residential radon exposure guideline in influencing
      individuals' health protection decisions. METHOD: Homeowners with known exposure
      levels in a high residential radon area (Winnipeg, Manitoba) were surveyed to
      document what they had done and spent to reduce their exposure to radon. The 507
      respondents were then re-surveyed to elucidate their response to hypothetical
      scenarios. Logistic regression was used to model risk reduction decisions as a
      function of exposure and other explanatory variables. RESULTS: Homeowners were
      only likely to have taken action to reduce exposure at levels exceeding 1,100
      Bq/m3, well above Canada's guideline of 800 Bq/m3. However, when informed of the
      guideline, respondents indicated they would act at exposures of 702 Bq/m3.
      INTERPRETATION: The Canadian residential radon exposure guideline, as it has been
      implemented, has not effectively prompted homeowner actions to reduce exposures
      to radon.

PMID- 12050993
TI  - Factors associated with missed eye examinations in a cohort with diabetes.
AB  - BACKGROUND: The diabetes screening program in Moosonee and Moose Factory, Ontario
      was evaluated to explore which factors may be associated with individuals who
      had/had not attended screening examinations for diabetic retinopathy. METHODS:
      Exposure data were collected from patient charts for basic demographic and
      medical history data. The main outcome of interest was the absence of a retinal
      examination in the two years preceding data collection. RESULTS: There were 248
      subjects identified with diabetes who had complete data for the variables of
      interest. On univariate analysis, younger age and shorter duration of diabetes
      were significantly associated with not having an eye examination. On multivariate
      analysis, younger age, residence in Moosonee, and shorter duration of diabetes
      remained in the final model. INTERPRETATION: Screening programs for diabetic
      retinopathy in the James Bay Cree should consider targeting younger individuals
      with diabetes of less than 5 years duration since this sub-group is not as likely
      to attend eye examinations.

PMID- 12050994
TI  - Is there regional variation in the SF-36 scores of Canadian adults?
AB  - BACKGROUND: Canadian normative data for the Medical Outcomes Study 36-item short
      form (SF-36) have recently been published. However, there is evidence from other
      countries to suggest that regional variation in health-related quality of life
      (HRQOL) may exist. We therefore examined the SF-36 data from nine Canadian
      centres for evidence of systematic differences. METHODS: Bayesian hierarchical
      modelling was used to compare the differences in the eight SF-36 domains and the
      two summary component scores within each of the age and gender strata across the
      nine sites. RESULTS: Five domains and the two summary component scores showed
      little clinically important variation. Other than a small number of exceptions,
      there was little overall evidence of HRQOL differences across most domains and
      across most sites. INTERPRETATION: Our finding of only a few small differences
      suggests that there is no need to develop region-specific Canadian normative data
      for the SF-36 health survey.

PMID- 12050995
TI  - Present state-of-the-art in elbow arthroplasty.
AB  - Prosthetic joint replacement of the elbow is, with some delay in comparison with
      the shoulder, the finger joints and especially the hip and knee joint, becoming a
      routine operation at least in more specialised orthopedic and trauma centers. In
      the seventies and eighties, more than 80% of the indications were in patients
      affected by rheumatoid arthritis, in which both sides were typically affected,
      seriously jeopardising their independence in activities of daily living. In the
      last decade an increasing number of posttraumatic osteoarthritic cases were
      included in the indications. Among the numerous prosthetic devices, only a few
      have stood the test of time (> 10 years); a meta-analysis of the world literature
      shows an average follow-up of less than 5 years. Two main types of prostheses
      must be distinguished, linked and non-linked. The linked prostheses are, with few
      exceptions, so-called sloppy hinges with a clearance between both components,
      permitting movement in the sagittal plane and in the frontal plane and also some
      rotation. Using the normal anatomical stabilising structures, the stresses on the
      interface are reduced. This type of linked prostheses has a wider range of
      possible indications than the non-linked resurfacing prostheses, which require a
      largely preserved bone stock and intact ligaments in order to avoid instability
      with subluxations or even dislocations. Resurfacing prostheses can be more or
      less constrained according to the degree to which they mimic normal elbow
      anatomy. In order to reduce the stresses on the interface, the more constrained
      resurfacing prostheses make additional use of an intramedullary stem. The
      fixation of the device in the bone is achieved with bone cement in nearly all the
      linked and non-linked prostheses. Sloppy hinges with condylar configurations (as
      the GSB III elbow prosthesis) or an anterior flange (Coonrad-Morrey) further
      reduce the stresses on the interface and have better long-term results. Special
      instruments help to place the prosthesis in correspondence to the normal center
      of rotation and to minimise the bone resection needed and the risk of intra
      operative complications (condyle fractures, shaft perforation). The results
      concerning pain relief and mobility are, for all properly placed prostheses, very
      satisfactory in the first years. A reliable account of long-term results (> 10
      years of non-interrupted series of elbow prostheses) has so far been given only
      by a few authors. In cases with rheumatoid arthritis the survival rate at 10
      years reaches 90%; the complication rate however is still definitely larger than
      with hip, knee and shoulder prostheses. This is particularly true for
      posttraumatic OA cases. Aseptic loosening, infection, instability and ulnar nerve
      lesions are at the fore and about twice as frequent as in RA, especially in
      patients below 60 years of age. In order to keep a safe retreat possibility open,
      we insist on the best possible preservation or reconstruction of normal anatomy
      (e.g. condyle reconstruction) when implanting an elbow prosthesis.

PMID- 12050996
TI  - Meniscal transplantation.
AB  - The aims of a meniscal replacement are: 1) to reduce the pain experienced by some
      patients following meniscus resection; 2) to prevent the degenerative changes of
      cartilage and the changes in subchondral bone following meniscus resection; 3) to
      avoid or reduce the risk of osteoarthritis following meniscus resection; 4) to
      restore optimally the mechanical properties of the knee joint after meniscal
      resection. The results of meniscus transplantation have been studied in animals.
      There is no proof from these experiments that replacement of a meniscus can
      reduce the risk of arthritis, but there are indications that it can decrease the
      development of cartilage degeneration. In humans, the results of meniscus
      transplantation have been reported in several series of patients, operated with
      different techniques. There are no controlled studies of meniscus replacement in
      humans. In case of meniscal allograft implantation surgery should be minimally
      invasive, not sacrificing the original meniscal insertion points. It appears
      preferable to use an open technique in medial transplantation, whereas the
      arthroscopic approach appears to allow for easier lateral implantation.

PMID- 12050997
TI  - Prevention of thromboembolic disease after non-cemented hip arthroplasty. A
      multimodal approach.
AB  - Thromboembolism following total hip arthroplasty is a common complication that
      may result in significant morbidity and mortality. Despite this, optimal
      prophylactic regimen is controversial. We investigated the efficacy of a
      comprehensive approach encompassing the use of aspirin, intermittent compression
      devices ('foot pumps'), and early mobilization in a cohort of 200 consecutive
      patients after non-cemented total hip replacements. The surgical procedures were
      carried out under epidural anesthesia in most cases (91%). All patients were
      allowed full weight bearing and received ambulation training starting on the
      first post-operative day. Ankle-high pneumatic boots ('foot pumps') and aspirin
      (325 mg p.o./qd) were used immediately after surgery. The presence of deep vein
      thrombosis was determined with the routine use of venous duplex scans on post
      operative day number 5 to 10 (mean 6.8). The duration of the follow-up was 3
      months. No patients were lost to follow-up. Four distal DVT's (2%) were detected
      in three patients. None of the patients developed symptomatic pulmonary embolism
      during the follow-up period. There were no major wound complications. Venous
      thromboembolic disease after hip replacement surgery is largely associated with
      postoperative immobilization and venous stasis. It is the authors' opinion that a
      prevention strategy should include mechanical as well as pharmacological
      measures. The concomitant use of epidural anesthesia, "foot pumps", aspirin and
      early full weight bearing ambulation may be effective in further reducing the
      incidence of DVT after surgery.

PMID- 12050998
TI  - Carpal tunnel syndrome despite negative neurophysiological studies.
AB  - The purpose of the present study was to compare the results of conservative and
      operative treatment for patients with carpal tunnel syndrome having normal
      neurophysiological studies. We studied 125 patients with normal
      neurophysiological studies and analysed eight symptoms and signs as "prognostic
      factors". Ninety-six patients were treated conservatively (splintage, steroid
      injection, antiinflammatory medications, activity modification) and 29 were
      treated surgically (open decompression). One year after initiation of treatment
      we assessed the outcome and statistically analysed (chi-square test) the
      differences between the two groups. We did not find any statistically significant
      correlation between "prognostic factors" and outcome. Twenty four percent of the
      group treated non-operatively had a good or excellent outcome, whereas 90% of the
      group treated operatively had a good or excellent outcome. This difference was
      statistically significant (p < 0.0001). Our study supports the view that the
      diagnosis of carpal tunnel syndrome is clinical and not neurophysiological. We
      now recommend operative treatment for these patients.

PMID- 12050999
TI  - The usefulness of the Phalen test and the Hoffmann-Tinel sign in the diagnosis of
      carpal tunnel syndrome.
AB  - Both the Phalen test and the percussion (Hoffmann-Tinel) test are considered to
      be the classic diagnostic tests for Carpal Tunnel Syndrome (CTS). Sensitivity of
      these tests, as given in the literature, ranges from 42 to 85% (Phalen) and from
      38 to 100% (Hoffmann-Tinel), and specificity from 54 to 98% and from 55 to 100%
      respectively. The objective of this study was to evaluate sensitivity and
      specificity of both tests and to analyse the influence of such selected factors,
      such as patient's age and duration of symptoms. The clinical group consisted of
      112 patients (147 hands) with CTS confirmed clinically and on nerve conduction
      studies. The control group of 50 patients (100 hands) was selected from hospital
      volunteers, who did not complain of any hand symptoms. Sensitivity and
      specificity of the Phalen test turned out to be respectively 85 and 89% and for
      the percussion test, 67 and 68%. There was no significant influence of patients'
      age upon the test results. Seventeen patients showed negative results for both
      tests, but in these individuals, the duration of symptoms was significantly
      longer than in the remaining group. These findings indicated essential diagnostic
      value for the Phalen test, but considerably smaller for the percussion test. In
      the diagnosis of long lasting syndromes, the usefulness of both tests is limited.

PMID- 12051000
TI  - Functional results after surgical repair of quadriceps tendon rupture.
AB  - We present the long-term results of surgical repair of a traumatic rupture of the
      quadriceps tendon in a group of 24 patients with a mean age of 58 years. There
      were 21 male and 3 female patients. Fifteen patients were seen for clinical
      control after a mean follow-up of 75 months and they all presented with some
      quadriceps muscle atrophy. Twelve patients had normal knee mobility, three had a
      flexion deformity of 10 degrees and two had less than 120 degrees of knee
      flexion. Active knee extension was normal in all patients. Three patients
      experienced some decrease in stability of their knee joint. Subjectively all
      patients were satisfied with the result. Nine patients underwent a Cybex-test for
      evaluation of the isokinetic force of knee flexion and extension, with a
      comparison between the injured and the uninjured side. For concentric force there
      was a mean deficit at low speed of 36.1% for the quadriceps muscle; at high speed
      it was 28.2%. For the knee flexors, the deficits were 30.7% and 27.2%
      respectively. Regarding eccentric force, the mean deficit for knee extensors was
      13.8% and 0.25% respectively and for knee flexors 6.5% and 5.5% respectively.

PMID- 12051001
TI  - Two-stage exchange of infected knee arthroplasty with an prosthesis-like interim
      cement spacer.
AB  - Two-stage revision in infected knee arthroplasty is standard practice. One
      problem during the interim period is soft tissue fibrosis. Attempts have been
      made to preserve leg length and ligament length by introducing spacers, usually
      made out of antibiotic-loaded bone cement. We present a new interim prosthesis,
      which is made intra-operatively out of polymethylmethacrylate (PMMA). Antibiotic
      loaded cement provides a therapeutic level of antibiotics in the periarticular
      soft tissue. We report the results in ten patients, who were treated with this
      prosthesis-like spacer and were prospectively studied. After an average follow-up
      of 13.5 months, there was no recurrent infection.

PMID- 12051002
TI  - Transient bone oedema of the tibia mimicking a tumorous process.
AB  - The authors describe a distinct clinical entity consisting of bony tenderness,
      increased isotope uptake along the metaphyses and/or diaphyses and magnetic
      resonance changes simulating a bone marrow-replacing lesion. Bone biopsies
      indicate the presence of bone marrow fibrosis and some new bone formation. Nine
      such cases were prospectively evaluated according to a standardized protocol
      including clinical examination, x-rays, bone scan and CT scan as well as MRI
      scans including contrast medium injection. All patients presented with tibial
      tenderness. In one case the bone was noticeably thicker as compared to the other
      side. The ages ranged from 6 years to 64 years and 6 of the patients were female.
      Xrays were normal in 6/9 patients; the rest had minimal periosteal reaction, and
      mild intramedullary sclerosis. Uniform imaging findings were longitudinal
      increased uptake along the metadiaphysis of the tibia on bone scans, and
      increased bone marrow density on CAT scans without a fracture line. A magnetic
      resonance study indicated bone marrow replacement as demonstrated by an area of
      low signal intensity on T1-weighted images and high signal intensity on T2
      weighted images. Some enhancement of signal was observed following gadolinium
      injection. This clinical entity, which the authors attribute to be a medullary
      stress reaction, is self-limited, and pain resolves within 3 months. However the
      radiographic changes appear to be permanent. A biopsy is not required provided no
      cortical penetration or soft tissue mass is demonstrated by MRI scan.

PMID- 12051004
TI  - Bilateral anterior shoulder dislocation--a case report and review of the
      literature.
AB  - Bilateral dislocations of the shoulders are uncommon. Of the cases which do
      present, the majority are posterior and occur secondary to seizures associated
      with epilepsy, electrocution and hypoglycaemia. Bilateral anterior dislocations
      are thought to be very rare. This report describes such a case which occurred
      following minor trauma in an elderly lady. The literature review which follows
      would seem to suggest that this may not be as rare as previously thought.

PMID- 12051005
TI  - Irreducible dorsal radiocarpal fracture dislocation with dissociation of the
      distal radioulnar joint: a case report.
AB  - We report a case of dorsal radiocarpal fracture dislocation with dissociation of
      the distal radioulnar joint. Closed reduction was unsuccessful due to
      interposition of the osteochondral fragments and open reduction and fixation was
      carried out with a satisfactory end result. The advantages of volar approach and
      use of external fixator in the management of this injury are discussed.

PMID- 12051006
TI  - Ulnopalmar dislocation of the fifth carpometacarpal joint. A rare injury.
AB  - Volar dislocation of the carpometacarpal joint of the little finger is an
      uncommon injury. It is subdivided in ulnopalmar and radiopalmar dislocations. The
      injury can easily be missed on standard x-rays. Closed reduction and K-wire
      fixation has commonly been used in the treatment, although closed reduction and
      casting has been reported. Only 10 cases of an ulnopalmar dislocation were
      published previously. We report a case of a simultaneous dislocation of the 4th
      metacarpophalangeal joint and an ulnopalmar dislocation of the 5th
      carpometacarpal joint. The combination of these injuries has not been reported
      yet. We review the available literature and discuss the methods of treatment.

PMID- 12051003
TI  - Filling of segmental bone defects in revision knee arthroplasty using morsellized
      bone grafts contained within a metal mesh.
AB  - For revision knee surgery with uncontained tibial bone defects, the authors
      report the containment of compacted morsellized allograft using metal-wire mesh,
      followed by implantation of a cemented total knee prosthesis. This method is
      comparable to the "impaction grafting technique" described for revision hip
      surgery and could be an alternative to metal wedges, augmented components, custom
      made implants, polymethyl-methacrylate or structural bone grafts to solve some
      problems of cavitary and segmental bone defects in revision total knee
      arthroplasty.

PMID- 12051007
TI  - Penetration injury of the hindfoot following intramedullary nail fixation of a
      tibial fracture.
AB  - Technical errors during intramedullary nail insertion are not uncommon. We report
      a case of tibial guide wire penetration into the distal tibial articular surface,
      the talus and the calcaneus during insertion of the nail with the ankle
      dorsiflexed. This has not been reported in the past. Computerized tomogram was a
      useful tool in the diagnosis. This complication was associated with long-standing
      ankle pain, which however eventually settled. We advise frequent use of biplanar
      C-arm image during the insertion of the guide wire, the reamer and tibial nail
      into the medullary canal of the tibia or other long bones. None of these
      instruments should be forced through. Once the knobbed guide wire is exchanged to
      a straight guide wire, the wire should not be forced through or reamed over, and
      the nail should be introduced over the guide wire with caution. Early
      intraoperative identification and recording of this iatrogenic accident is
      necessary in order to explain the situation to the patient and modify treatment
      accordingly.

PMID- 12051009
TI  - Acute paraplegia due to thoracic extramedullary hematopoiesis in chronic
      myeloproliferative disorder--an unusual presentation.
AB  - Spinal cord compression due to extramedullary hematopoiesis is a well-known
      complication in a number of hematological diseases. Most of the patients present
      with progressive paraparesis due to the slow expansion of the extramedullary
      hematopoietic tissue. The authors report a case of chronic myeloproliferative
      disorder with spinal extramedullary hematopoiesis presenting with acute
      paraplegia. Chronic myeloproliferative disorder is an uncommon cause of spinal
      cord compression, especially when associated with acute paraplegia. The authors
      discuss the pathomechanism of this unusual presentation.

PMID- 12051008
TI  - [Prosthetic hip joint infection caused by Listeria monocytogenes].
AB  - The authors report an unusual case of prosthetic hip joint infection caused by
      Listeria monocytogenes. The patient, an 87-year-old lady who had undergone a
      right total hip replacement 10 years previously, presented with pain and
      restriction of hip motion three weeks after an episode of abdominal pain.
      Aspiration of the joint yielded a dark fluid, from which Listeria Monocytogenes
      type 4-b was isolated. Blood cultures remained negative. After prolonged
      antibiotic therapy, symptoms gradually resolved. A few months later, pain
      recurred with radiological signs of loosening of the femoral component. One-stage
      revision arthroplasty was performed combined with antibiotic treatment. The
      patient remains asymptomatic at one year follow-up. Laboratory data and x-ray
      control are normal. Prosthetic hip joint infection with Listeria monocytogenes is
      uncommon; few cases have been reported. The literature review shows that
      prolonged antibiotic therapy alone may be used in patients for whom removal of
      the prosthesis is not desirable, although revision arthroplasty or prosthesis
      removal remains necessary in the other cases.

PMID- 12051010
TI  - Self-help group Reflex Sympathetic Dystrophy (RSD).

PMID- 12051011
TI  - Association of psychological distress with psychological factors in rescue
      workers within two months after a major earthquake.
AB  - BACKGROUND AND PURPOSE: Studies of the health of rescue workers after a major
      disaster have frequently focused on posttraumatic stress disorder. This study
      aimed to determine the characteristics of psychological distress and its
      psychosocial predictors in rescue workers within a 2-month period after an
      earthquake that struck central Taiwan on September 21, 1999. METHODS: A total of
      1,104 rescue workers serving in the earthquake were enrolled in the study.
      Psychological distress was measured using the Brief Symptom Rating Scale (BSRS),
      personality traits using the Maudsley Personality Inventory (MPI), and family
      function using APGAR (adaptability, partnership, growth, affection, and resolve)
      indexes. These measurements were performed within 2 months of the earthquake.
      Univariate and multivariate analyses were applied to examine the association
      between psychological distress and various psychosocial factors. RESULTS: BSRS
      assessment revealed severe psychological distress in 137 (16.4%) subjects. The
      most common symptom dimension was phobic-anxiety (18.7%), followed by hostility
      (17.6%), obsessive-compulsive symptoms (16.2%), depression (14.9%), paranoid
      ideation (14.2%), interpersonal sensitivity (13.3%), psychoticism (11.9%),
      anxiety (10.8%), additional symptoms (8.5%), and somatization (6.2%). Pre
      disaster major life events (R2 = 0.03) and most of the factor scores of the MPI
      (including moodiness, anxiety-prone, outgoing, conscientiousness, activity, and
      sociability factors; R2 = 0.25) predicted the severity of psychological distress.
      Time of arrival at the scene, previous exposure, age, and family function had no
      or trivial predictive power. CONCLUSION: The results of this study indicated that
      prevalence of general psychological distress is high among rescue workers in the
      first 2 months after a major earthquake. Personality traits and pre-disaster life
      adjustment had a dominant predictive power for psychological distress. Immediate
      psychosocial intervention should be considered to ameliorate the distress related
      to disaster rescue work.

PMID- 12051012
TI  - Coronary arteriovenous fistula in pediatric patients: a 17-year institutional
      experience.
AB  - BACKGROUND AND PURPOSE: Coronary arteriovenous fistula (CAVF) is a rare
      congenital anomaly in pediatric patients. Its clinical manifestations vary
      considerably and its long-term outcome is not fully understood. This study sought
      to determine the natural history and long-term outcome in CAVF patients treated
      over a 17-year period at Cathay General Hospital in Taipei. MATERIALS AND
      METHODS: The medical records of all 10 pediatric patients (five boys and five
      girls aged between 15 days and 15 years) with CAVF treated from 1983 through 2000
      at our hospital were reviewed. Data collected included symptoms and signs, the
      findings of electrocardiography, echocardiography, catheterization, and
      angiography, and surgical results. RESULTS: CAVF was diagnosed on the basis of
      color Doppler echocardiography in eight patients and by cardiac catheterization
      and angiography in two. Congestive heart failure was found in four patients and
      both myocardial ischemia and infarction were found in two patients. Most of the
      affected coronary arteries were tortuous and dilated with a mean diameter of 12.6
      mm (range 5-40 mm). Under cardiopulmonary bypass, fistulous terminations were
      sutured in seven patients, three of whom were found to have multiple fistulous
      openings. Postoperative follow-up examinations revealed that all of the affected
      coronary arteries and fistulas remained dilated and tortuous, except in one
      patient. Two patients who had distal CAVF developed coronary thrombus,
      calcification, and ventricular aneurysm at 2 and 10 years after operation,
      respectively. Another patient developed fistulous recanalization 7 years after
      operation, but this abnormal channel had disappeared again 3 years after
      recanalization. One patient developed an iatrogenic CAVF 8 years after surgical
      repair of tetralogy of Fallot. CONCLUSIONS: Unlike adults, pediatric patients
      with CAVF tend to be symptomatic. Ligation of the fistulous termination alone
      does not reduce the size of the fistula. Our findings indicate that long-term
      follow-up is essential due to the possibility of postoperative recanalization,
      persistent dilation of the coronary artery and ostium, thrombus formation,
      calcification, and myocardial infarction. In addition, postoperative antiplatelet
      therapy is recommended, especially in patients with distal CAVF and abnormally
      dilated coronary arteries.

PMID- 12051014
TI  - Mitochondrial calcium ion and oxidative phosphorylation in regenerating rat
      liver.
AB  - BACKGROUND AND PURPOSE: Liver regeneration develops after partial hepatectomy.
      This study investigated the enhancement of oxidative phosphorylation in liver
      regeneration and its correlation to mitochondrial calcium ion in rats. METHODS:
      Respiratory functions of mitochondria isolated from regenerating rat liver 24,
      48, 72, and 96 hours after 70% hepatectomy were studied including state 3 and
      state 4 oxygen consumption, respiratory control (RC) ratio, and ADP/O (molecules
      of adenosine diphosphate production per molecule of oxygen). Intramitochondrial
      matrix free calcium ion concentration ([Ca2+]m) was measured using the fluo-3
      loading method. The changes in state 3 oxygen consumption and [Ca2+] were also
      evaluated in chloramphenicol-treated mitochondria, which were isolated from rats
      subjected to chloramphenicol injection for 48 hours. RESULTS: State 3 oxygen
      consumption was significantly enhanced 48 hours post-hepatectomy. The RC ratio
      also reached a peak value 48 hours after hepatectomy. No significant change was
      found in state 4 oxygen consumption and ADP/O during the first 96 hours after
      hepatectomy. The [Ca2+]m was significantly elevated as early as 24 hours post
      hepatectomy, and reached its peak value 48 hours post-hepatectomy. The
      mitochondrial total calcium concentration was also elevated at 24 hours post
      hepatectomy, but returned to near the control level 48 hours post-hepatectomy. In
      the chloramphenicol-treated group, state 3 oxygen consumption was depressed at 48
      hours compared to the post-hepatectomy group, while the [Ca2+]m was significantly
      increased. CONCLUSIONS: The energy demand for liver regeneration is enhanced
      after partial hepatectomy. [Ca2+]m corresponds well to this energy demand,
      suggesting it may play an important role in the process of liver regeneration.

PMID- 12051013
TI  - Association between molecular variants of the angiotensinogen gene and
      hypertension in Amis tribes of eastern Taiwan.
AB  - BACKGROUND AND PURPOSE: Molecular variants (M235T and T174M) in the
      angiotensinogen (AGT) gene and a mutation in the promoter region that involves
      the presence of an adenine (A) instead of a guanine (G) 6 bp upstream from the
      transcription initiation site (G-6A) have been reported to have a positive
      correlation with hypertension. This study evaluated the association of the M235T,
      T174M, and G-6A mutations of the AGT gene with hypertension in Taiwanese
      aboriginals. METHODS: This case-control study recruited 107 subjects with
      hypertension and 96 normotensive subjects from the Amis tribes of eastern Taiwan.
      Genomic DNA was amplified using the polymerase chain reaction (PCR) and the PCR
      product was analyzed using automated sequencing. RESULTS: The frequencies of MM,
      MT, and TT genotypes at amino acid 235 were different between hypertensive (1%,
      13%, 86%) and normotensive subjects (0%, 30%, 70%; p = 0.008), whereas the 174
      variants of the AGT gene were not different between these two groups (1%, 14%,
      85% in hypertensives, 1%, 17%, 82% in normotensives; p = 0.868). The distribution
      of GG, GA, and AA genotypes differed between the two groups (1%, 15%, 84% in
      hypertensives vs 1%, 31%, 68% in normotensives; p = 0.021). The frequency of the
      235T allele was higher among hypertensives than normotensives (93 vs 85%; p =
      0.015) and the odds ratio for association with the 235T allele (vs 235M) in
      hypertensives was 2.20. The frequency of the 174M allele was not different
      between the two groups (1 vs 1%). The frequency of the -6A allele was higher
      among hypertensives (83 vs 68%; p = 0.011) and the odds ratio association of
      hypertension with the -6A allele (vs -6G) was 2.18. Haplotype analysis showed
      that the -6A-235T allelic frequencies significantly differed between the two
      groups (chi 2 = 1.39, P = 0.001). CONCLUSIONS: The prevalences of the 235T and 
      6A variants of the AGT gene in the Amis tribes of eastern Taiwan are high and are
      significantly associated with hypertension, whereas the 174M variant is not. The
      haplotype combining the 235T and -6A variants is also associated with
      hypertension. The prevalences of the 235T allele and -6A allele in this study and
      other studies in ethnic Chinese subjects are higher than those in Japanese.

PMID- 12051015
TI  - Radical hysterectomy alone or combined with neoadjuvant chemotherapy in the
      treatment of early stage bulky cervical carcinoma.
AB  - BACKGROUND AND PURPOSE: Early-stage bulky cervical carcinoma treated with
      conventional surgery or radiotherapy has a higher rate of recurrence compared to
      smaller tumors at the same stage. Whether neoadjuvant chemotherapy prior to
      radical hysterectomy can improve survival in early-stage bulky cervical carcinoma
      remains unclear. This study was designed to answer this question. METHODS: Fifty
      eight women with early-stage bulky cervical cancer were included in this
      retrospective study. Thirty-one had received neoadjuvant chemotherapy before
      radical hysterectomy, and the other 27 patients underwent surgery alone. The
      chemotherapeutic regimen was a combination of cisplatin, vincristine, and
      bleomycin with a 10-day interval for two to three courses. RESULTS: The age,
      parity, and tumor diameter before treatment in the two groups were similar. The
      mean tumor diameter was significantly decreased after neoadjuvant chemotherapy
      (4.6 +/- 0.8 vs 3.4 +/- 1.5 cm, P = 0.003). Patients without neoadjuvant
      chemotherapy had a significantly higher incidence of parametrial invasion (14/27
      vs 7/31, P = 0.022). More involved lymph nodes were found during surgery in
      patients without neoadjuvant chemotherapy (23.1 +/- 10.5 vs 17.4 +/- 7.1, P =
      0.024), but the incidence of lymph node metastasis was not different between the
      two groups (18/31 vs 17/27, P = 0.71). The response rate of primary tumor to
      chemotherapy was 48.4% (15/31). No significant differences in clinical and
      pathologic parameters were found between responders and non-responders. Deep
      stromal invasion (> or = 3/4 thickness of cervical stroma) was the only
      independent prognostic factor for disease-free survival (DFS) and overall
      survival (OS) in the 58 patients and in the 31 patients who received neoadjuvant
      chemotherapy. Neither neoadjuvant chemotherapy nor the response to it was an
      independent prognostic factor for DFS or OS. CONCLUSIONS: Neoadjuvant
      chemotherapy could reduce the incidence of local invasion for bulky early-stage
      cervical carcinoma but did not improve the DFS or OS in our patients. Without
      further randomized study of the effects of neoadjuvant chemotherapy, this
      treatment should be chosen carefully.

PMID- 12051016
TI  - Neonatal outcome of infants born after in vitro fertilization at National Taiwan
      University Hospital.
AB  - BACKGROUND AND PURPOSE: This study compared the neonatal outcome between infants
      born after in vitro fertilization (IVF) and after natural conception at National
      Taiwan University Hospital. METHODS: All medical records of women who underwent
      IVF and gave birth at our hospital from January 1995 to December 1996 were
      reviewed. The charts of their offspring were also reviewed. We compared the
      neonatal outcome of infants born after IVF with that of infants born after
      natural conception. Neonatal outcome was evaluated based on preterm birth, very
      low birth weight (VLBW), perinatal morbidity, and neonatal mortality. RESULTS: A
      total of 75 women underwent IVF and gave birth to a total of 100 live newborns
      and two fetuses with intrauterine death during the 2-year study period. Among
      these newborns, the prevalence of preterm birth was 28%, of perinatal morbidity
      was 17%, and of neonatal mortality was 3%, which were significantly higher than
      those among the 7,736 neonates born after natural conception. However, the rate
      of VLBW was similar between the two groups. The rate of preterm birth for twin
      pregnancies were higher than that for singleton pregnancies in both groups.
      CONCLUSION: This study showed that infants born after IVF had a higher risk of
      preterm birth and higher perinatal morbidity and neonatal mortality.

PMID- 12051017
TI  - Clinical characteristics of Taiwanese hereditary non-polyposis colorectal cancer
      kindreds.
AB  - BACKGROUND AND PURPOSE: The prevalence of colorectal cancer in Taiwan has
      increased gradually in recent years. Around 5% to 15% of colorectal cancer is
      hereditary, and hereditary nonpolyposis colorectal cancer (HNPCC) is the most
      common form of hereditary colorectal cancer. This study aimed to determine the
      clinical characteristics of Taiwanese HNPCC kindreds. PATIENTS AND METHODS: We
      reviewed the chart records of all HNPCC kindreds followed-up in our hospital
      during the period from 1996 to 1999. Their clinical characteristics were recorded
      and analyzed. RESULTS: There were 10 families, including a total of 202 persons,
      who met the Amsterdam criteria for HNPCC. Fifty-two persons in these families had
      a diagnosis of cancer, including 26 women and 26 men. There were 40 colorectal
      cancers, five endometrial cancers, five gastric cancers, two ovarian cancers, two
      hepatocellular carcinomas, and one each of lung cancer, breast cancer, thyroid
      cancer, and pancreatic cancer (six patients had two cancers). The mean age at
      cancer diagnosis was 42.1 years. Among the 12 occurrences in 11 colorectal cancer
      patients with complete clinical and pathological findings, most cancers (67%)
      were located proximal to the splenic flexure (right-side colon). One patient had
      metachronous colorectal cancer. CONCLUSIONS: This is the first report of the
      general clinical characteristics of Taiwanese HNPCC. The clinical characteristics
      of HNPCC in Taiwan were similar to those in Western countries. The genetic bases
      of Taiwanese HNPCC patients remain to be determined.

PMID- 12051018
TI  - Osteonecrosis of the femoral head in a human immunodeficiency virus type 1
      infected patient with lipodystrophy.
AB  - Osteonecrosis of the femoral head is rare in human immunodeficiency virus (HIV)
      infected patients. We describe a 37-year-old HIV-infected man who developed
      lipodystrophy after highly active antiretroviral therapy (HAART), leading to left
      leg disability. Radiography revealed osteonecrosis of the left femoral head,
      which appeared to be related to the antiretroviral therapy for HIV infection and
      subsequent development of lipodystrophy and hyperlipidemia. While osteonecrosis
      among Taiwanese HIV-infected patients is uncommon, the potential for the
      development of this long-term complication should be carefully monitored as more
      patients survive for longer periods after HAART.

PMID- 12051019
TI  - Sensory neuropathy in X-linked recessive bulbospinal neuronopathy.
AB  - X-linked recessive bulbospinal neuronopathy (X-BSN) is an adult-onset spinal and
      bulbar amyotrophy. Neurophysiologic studies demonstrate subclinical involvement
      of sensory nerves with diminished or absent sensory nerve action potientials and
      denervation changes, indicating the involvement of sensory neurons. We report the
      clinical features, findings of electrophysiologic study, and results of
      morphometric analysis of sural nerve pathology in a patient with X-BSN. Molecular
      genetic studies were also performed in the patient and his three daughters.
      Electrophysiologic studies revealed decreased amplitude sensory nerve action
      potentials and the presence of high amplitude motor unit potentials in all
      muscles tested. Sural nerve biopsy demonstrated axonal degeneration with a
      predominant loss of large myelinated fibers. Molecular genetic studies confirmed
      elongation of the CAG triplet repeats in exon 1 of the androgen receptor gene.
      Sequence analysis of the androgen receptor gene revealed that the number of CAG
      triplet repeats was 45 in the patient and was 45 to 48 in the mutant allele but
      only 19 to 30 in the normal allele in his three daughters. These findings suggest
      that both motor and sensory neurons are involved in X-BSN. Sural nerve biopsy and
      molecular genetic analysis are helpful in differentiation between X-BSN and other
      motor neuron diseases.

PMID- 12051020
TI  - Detection and treatment of an asymptomatic case of early esophageal cancer using
      chromoendoscopy and endoscopic mucosal resection.
AB  - Recent trends in the management of superficial esophageal cancer consist of
      improved detection and curative endoscopic therapy. However, successful
      endoscopic therapy has not been reported in Taiwanese patients with this disease.
      We describe the case of a male, 38-year-old habitual drinker admitted for a
      general health check-up, whose endoscopic examination revealed a slightly
      depressed discolored lesion in the middle esophagus. Chromoendoscopy with 3%
      Lugol's iodine solution showed a mesh-like unstained pattern occupying
      approximately two-thirds of the circumferential esophageal mucosa. Spraying with
      2% toluidine blue solution stained a 3 x 6 cm suspect area pale blue. Endoscopic
      biopsy confirmed squamous cell carcinoma. Histopathologic examination revealed
      the lesion was a type IIc superficial esophageal cancer. Endoscopic
      ultrasonography showed the lesion was limited to the epithelial layer with no
      evidence of lymph node involvement. The lesion was removed en bloc using
      endoscopic mucosectomy. Microscopic examination of the resected specimen
      demonstrated that the depth of invasion was confined to the epithelial layer
      except for some areas with small nests of tumor cells within the lamina propria.
      Balloon dilatation to prevent post mucosectomy stricture was performed and the
      patient recovered uneventfully. At 1 year of follow-up, the patient was alive
      without any endoscopic signs of local recurrence. This case suggests that
      chromoendoscopy in combination with endoscopic resection is likely to benefit
      patients with early-stage esophageal cancer.

PMID- 12051021
TI  - High-dose steroid pulse therapy for the treatment of severe alopecia areata.
AB  - Growing evidence shows alopecia areata (AA) to be a T cell-mediated organ
      specific autoimmune disease. This study aimed to evaluate the efficacy of high
      dose steroid pulse therapy in Taiwanese patients with severe widespread AA
      exceeding 40% of the scalp. A total of 17 Taiwanese patients with severe AA
      lasting less than 2 years were treated once monthly at the outpatient clinic for
      six sessions. Children younger than 12 years of age received oral prednisolone (5
      mg/kg) in three divided doses, while for adults, 500 mg methylprednisolone was
      infused intravenously over 2 hours. Patients with multifocal AA exhibited the
      most favorable response, with more than 75% hair regrowth (9/11). Relapse
      occurred in two patients at 4 and 8 months after the last treatment,
      respectively. One patient with ophiatic AA showed a transient response, but
      subsequently lost hair even upon continuation of therapy. Two patients of four
      with alopecia totalis had full hair regrowth but one lost hair again 6 months
      later. In the only patient with alopecia universalis, less than 10% hair regrowth
      occurred. No major side effects were observed. In summary, 11 of 17 patients
      (64.7%) had more than 75% hair regrowth after steroid pulse therapy. Our results
      indicated that steroid pulse therapy, given at 5-10 mg/kg once monthly for an
      average of 6 months, is effective and well tolerated in Taiwanese patients with
      severe multifocal AA lasting less than 2 years.

PMID- 12051022
TI  - Increased epithelial cell proliferation in nasal polyps.
AB  - BACKGROUND AND PURPOSE: The mucociliary function of the sinonasal mucosa is an
      innate defense mechanism of the human nasal airway. Epithelial cell proliferation
      is required for cell renewal and repair of the sinonasal mucosa. In this study,
      the MIB-1 monoclonal antibody, which can detect the S-phase nuclear protein Ki
      67, was used to evaluate the proliferation of the sinonasal mucosa in patients
      with various inflammatory conditions of the sinonasal mucosa. METHODS: Specimens
      from the inferior turbinates of patients with nasal allergy (n = 12), vasomotor
      rhinitis (n = 20), nasal polyps (n = 22), and control subjects undergoing
      rhinoplasty (n = 5) and mucosa of chronic sinusitis patients [inferior turbinates
      (n = 10), middle turbinates (n = 10), and maxillary sinus (n = 9)] were fixed in
      neutral formalin and embedded in paraffin. MIB-1 monoclonal antibody was used to
      detect proliferation of epithelial cells. RESULTS: Significantly increased
      epithelial cell proliferation was noted in nasal polyps compared to sinonasal
      mucosa. There was no difference among various sinonasal inflammatory conditions
      between patients and controls. CONCLUSIONS: Increased epithelial cell
      proliferation in nasal polyps may play an important role in covering the
      epithelial defects caused by the rupture of the epithelium and prolapse of
      connective tissue in nasal polyps.

PMID- 12051023
TI  - The case for standards for youth in custody in Canada.
AB  - Canada has no standards, procedural guidelines, or protocols for best practices
      in the care of youths in custody. This paper argues that clear, enforceable
      standards are important in defining a benchmark of acceptable practice. It argues
      that without standards, issues may arise which can create further difficulty for
      youths who are under the care of the state. It suggests that the current legal
      framework for standards is insufficient in its enforceability and its clarity.
      The new Youth Criminal Justice Act (YCJA) provides the Canadian government with a
      timely and much-needed opportunity to establish standards of care for youths in
      custody. Indeed, the YCJA contains specific, comprehensive, and relevant
      provisions that can be seen as laying a firm foundation for standards of care.

PMID- 12051024
TI  - An evaluation of residential treatment programs for young offenders in the
      Waterloo region.
AB  - This paper chronicles a comprehensive evaluation of 6 residential facilities for
      young offenders located within the region of Waterloo. Two kinds of research
      methodologies were employed in the investigation. One was primarily quantitative
      in nature, involving the completion of standardized scales for each of the youths
      who participated in the study (N = 129). The other was qualitative in nature, and
      involved interviews with a small sample of "graduates" from the centres (N = 9),
      and some of their parents and guardians (N = 4). Residential treatment was
      associated with significant improvements on the 2 measures developed specifically
      for the evaluation: a measure which focused on the specific goals which had been
      assigned to youths while in the program (Catalogue of Goals for Youth in
      Residence), and the global index of youth functioning which was empirically
      generated from residential case files (Inventory of Work Life and Social Skills).
      Qualitative interviews with program graduates and selected parents and guardians
      generally confirmed the positive evaluation of the impact of residential
      facilities on youths and served as the foundation for a series of recommendations
      for programmatic modifications and improvements.

PMID- 12051025
TI  - An impressionistic view of Canadian juvenile justice: 1965 to 1999.

PMID- 12051026
TI  - Restorative justice: lessons in empathy and connecting people.

PMID- 12051027
TI  - Young offenders and their communities: reframing the institution as an extension
      of the community.
AB  - This paper makes a case for using the institution as an extension of community
      resources rather than as a place for the exclusion of young offenders. This
      argument is built on 2 case studies that highlight the importance of treating
      young offenders in their own community and the need for permeable boundaries
      between institutions for young offenders and their communities. It is shown that
      processing youths as young offenders without helping them to maintain a sense of
      belonging to the community threatens their identity. Collaboration between
      institutions and communities to address the root causes of problems presented by
      at-risk youths and their families is as important for serious offenders as for
      their less delinquent peers. While the Youth Criminal Justice Act does not
      preclude movement in this direction, it is ambiguous about the development of
      community alternatives for serious offenders.

PMID- 12051028
TI  - Understanding aggression with adolescent girls: implications for policy and
      practice.
AB  - Seventy at-risk adolescent girls in 7 residential facilities were interviewed
      over a 12-month period. The girls were asked questions regarding experiences,
      thoughts, and feelings about physical and verbal fights with friends and parents.
      Results showed that many of these girls reported different reasons for starting
      and escalating verbal and physical fights, they had more negative feelings for
      verbal fights than for physical fights, and had similar thought processes during
      both kinds of fights. More girls acknowledged responsibility for starting fights
      with parents than they did with peers. Implications of the results for treatment
      of female young offenders and the development of public policy are discussed.

PMID- 12051029
TI  - Young offenders: balancing control and treatment.

PMID- 12051030
TI  - Doing better with "bad kids": explaining the policy-research gap with conduct
      disorder in Canada.
AB  - Conduct disorder (severe and persistent antisocial behaviour in children and
      youth) is an important community mental health problem in Canada and has been the
      focus of considerable recent public policy debate. Good research evidence is
      available on effective (and ineffective) interventions for conduct disorder.
      Paradoxically, however, relatively little of the research evidence is
      incorporated into policy decision-making. There is a policy-research gap. An
      example (Hamilton, Ontario) is used to illustrate this gap. The gap is then
      explained using a framework for health policy analysis that incorporates values,
      institutional structures, and information. Values and institutional structures
      greatly outweigh research evidence in influencing current Canadian policy-making
      for the problem of conduct disorder. Possibilities for improving the situation
      are suggested.

PMID- 12051031
TI  - [Mobilizing community around the lack of preventive measures against crime among
      10- and 11-year-old children].
AB  - Originality and relevance are not the only factors in the success of innovative
      programs. Community consensus, expertise and credibility of staff, and evaluative
      approaches are important as well. Virgule ("Comma"), a program aimed at helping
      10- and 11-year-olds who are first offenders, has these characteristics. The
      temporary hitch in the youth's life is viewed not as a definitive failure but as
      an opportunity for change. This is Virgule's philosophy: "Changing a period into
      a comma means changing a difficulty into a reason for progress."

PMID- 12051033
TI  - Long-term blues. Nursing homes to Congress: we really need Medicare.

PMID- 12051032
TI  - Youth justice reform and the rights of the child: a step forward or backward?
AB  - Our purpose is to examine Canada's new Youth Criminal Justice Act in light of
      Canada's obligations under the UN Convention on the Rights of the Child and in
      contrast to the Young Offenders Act. After reviewing the Convention and the Young
      Offenders Act, we examine the new act to determine its consistency with the
      Convention. We conclude that the new act is a step forward because of its greater
      focus on rehabilitation and social reintegration. However, it is an inadequate
      step because it does not fully ensure the protection, provision, and
      participation rights of the child as defined by the Convention.

PMID- 12051035
TI  - Hey, parents: this won't hurt a bit. Yes, you can talk to your kids about sex.

PMID- 12051034
TI  - Risky business.

PMID- 12051036
TI  - Little patients.

PMID- 12051037
TI  - Got calcium?

PMID- 12051038
TI  - Fixing a growing problem. New charts give a fairer picture of how kids develop.

PMID- 12051039
TI  - A safety net for parents. Some drug prescriptions aren't meant to be filled.

PMID- 12051040
TI  - Bringing doctors to day care.

PMID- 12051041
TI  - Know your genes, know yourself.

PMID- 12051042
TI  - [Poliomyelitis and its sequelae].

PMID- 12051043
TI  - [Poliomyelitis].

PMID- 12051044
TI  - [Ultrasound-guided insertion of central venous catheter via internal jugular
      vein].

PMID- 12051045
TI  - [Scabies].
AB  - The aim of this review is to draw attention to the fact that scabies still causes
      clinical problems and gives rise to epidemics in hospitals and institutions. We
      describe the clinical aspects of ordinary and crusted scabies and newer
      diagnostic methods, such as epiluminescence microscopy and PCR. The current
      treatment of scabies in Denmark is mentioned, and the importance of simultaneous
      preventative treatment of household contacts and hygienic measures in the
      surroundings is emphasised. The role of ivermectin in the treatment and
      prevention is briefly described. A series of scabies epidemics in hospitals and
      institutions are discussed with emphasis on factors influencing the spread and
      subsequent interruption of the epidemic. It is concluded that each institution
      should have guidelines for the handling of such epidemics and that the local
      hygiene unit should be involved immediately in the case of an epidemic.

PMID- 12051046
TI  - [Post-polio syndrome--symptomatology and measures].
AB  - New or increased symptoms often appear decades after the onset of polio. The
      definition of post polio syndrome (PPS) is: a confirmed history of polio, an
      interval of functional stability after initial recovery, non-disuse increased
      muscle weakness, and other complaints such as increased general fatigue and pain.
      Loss of motor units is compensated by collateral re-innervation and hypertrophy
      of muscle fibre. An elevenfold times increase in the motor unit region can be
      seen, and around double the muscle fibre area, corresponding to a fivefold
      increase in the number of muscle fibres in the motor unit. When loss of motor
      neurons can no longer be compensated for, muscle strength will decrease.
      Respiratory problems are present in a minority, but these need special attention
      and intervention. Evaluation and support through a special polio clinic is of
      value. The trainability varies according to the type and degree of polio changes.
      There may be a need for technical aids, especially for mobility, but time must be
      allowed for patients to accept reduced physical activity and changes in life
      habits recommended.

PMID- 12051047
TI  - [Myelography, can it be performed as an outpatient procedure?].
AB  - The modern contrast agents used today in myelography cause far fewer
      complications than earlier. This development has opened up the prospect of
      undertaking myelography as an outpatient procedure. The complications that can
      occur after the myelography are, for the great majority known, benign, and
      disappear within a few days, mainly headache. The frequency of minor
      complications can be minimised by the use of a smaller gauge and/or a rounded
      needle tip. When the procedure is done by experienced personnel with non-toxic
      antiseptic preparation, the complications seem to be similar in frequency,
      magnitude, and type to a simple diagnostic spinal tap. Positioning of the
      patients after the examination does not affect the frequency or seriousness of
      the complications. Our study of the patients' attitude towards outpatient
      myelography shows great satisfaction with the procedure. We therefore conclude
      that there is no added risk in performing outpatient myelography; the only
      noticeable complication is headache, which seldom needs intervention, and there
      are considerable benefits for both patients and hospital in an outpatient
      procedure.

PMID- 12051048
TI  - [Blunt isolated pancreatic trauma. Diagnostic problems--a clinical and
      radiological challenge].
AB  - INTRODUCTION: Blunt isolated pancreas trauma is rare, but it is a very serious
      condition. Diagnosis and treatment are often delayed, which considerably
      increases morbidity. The delay is caused by uncharacteristic symptomatology and
      the application of paraclinical and radiological diagnostic methods of low
      initial sensitivity and specificity. The aim of this study was to describe the
      diagnostic difficulties and the applicability of the various radiological
      modalities. MATERIAL AND METHODS: During the period 1995-2000, three patients
      with blunt isolated pancreas trauma were treated, and the case reports were
      examined retrospectively. RESULTS: All three showed classical mechanisms of
      injury, and a characteristic delay in diagnosis and treatment of 24 to 48 hours
      was seen. DISCUSSION: The frequent delay in diagnosis and subsequent treatment of
      the blunt pancreas trauma requires a more optimal strategy for handling such
      traumas. We recommend the following diagnostic algorithm: Repeated measurements
      of serum amylase initially. Image diagnostics with a dynamic spiral CT-scan with
      both oral and intravenous contrast. The CT scan is to be repeated or supplemented
      by MRCP on continued suspicion of pancreas injury, even when the initial CT scan
      shows normal findings.

PMID- 12051049
TI  - [The association between physical workload and low back pain clouded by the
      "healthy worker" effect].
AB  - INTRODUCTION: Both physical and psychosocial workplace factors are considered
      risk factors for low back pain (LBP). However, today, no consensus has been
      reached regarding the exact role of these factors in the genesis of LBP. MATERIAL
      AND METHODS: Questionnaire data were collected at baseline for 1,397 (and after
      five years for 1,163) men and women aged 31-50 years at baseline. LBP (any LBP
      within the past year; LBP < or = 30 days in total during the past year; LBP > 30
      days in total during tha past year) was analysed in relation to physical workload
      (sedentary, light physical, and heavy physical work) using logistic regression
      and controlling for age, gender, and social group. The proportions af workers
      changing between the workload groups over the five-year period were analysed in
      relation to LBP status. RESULTS: A baseline no statistically significant
      differences in LBP outcomes were found for workers exposed to sedentary, light
      physical, or heavy physical work. This was true for both genders and all age and
      social groups. At follow-up these was a statistically significant dose-response
      association between any LBP and long-standing LBP during the past year and
      increasing physical workload at baseline, also after controlling for age, gender
      and social group. Subjects with a heavy physical workload at baseline changed
      significantly more often to sedentary work, if they had experienced LBP for more
      than 30 days out of the past year. DISCUSSION: Having a sedentary job might have
      a protective or neutral effect in relation to LBP, whereas having a heavy
      physical job constitutes a significant risk factor. Because og migration between
      exposure groups (the "healthy worker" effect), longitudinal studies are necessary
      for investigating the associations between physical workload and LBP.

PMID- 12051050
TI  - [Injured elderly victims of bag-snatching treated at Odense University Hospital
      1996-2000].
AB  - INTRODUCTION: In recent years, a number of elderly patients have been treated at
      the Odense University Hospital following injuries caused by bag-snatching. The
      aim of this study was to discover how many of elderly patients sustained such
      injuries. MATERIAL AND METHODS: The study comprised all inhabitants in the Odense
      Municipality aged 60 years or more treated at Odense University Hospital in 1996
      2000 for injuries caused by bag-snatching. RESULTS: We registered 95 patients.
      The annual number rose significantly from 1996 to 1999 and from 1999 to 2000 it
      declined. The mean age was 78 years and 95% were women. Most of the injuries
      occurred during the daytime. Many patients were injured, because of falls as the
      bag-snatcher grabbed the bag and got away (74%). Fewer patients were beaten or
      kicked (26%). The patients were generally pedestrians (86%), and the bag
      snatchers mostly pedestrians (47%) or cyclists (29%). The injuries were commonly
      contusions/sprains (45%) and fractures/dislocations (37%). Twenty-seven per cent
      were admitted to hospital with a median stay of 15 days (1-54 days). One patient
      died as a result of the injury. Most patients sustained minor injuries (Maxsimal
      abbreviated injury scale-score = 1) (62%). DISCUSSION: Over a period of years we
      have observed an increasing number of injuries in the elderly caused by
      bagsnatching. The victims often fell and fractured or dislocated a limb. More
      than a quarter of the victims were hospitalised.

PMID- 12051051
TI  - [Institutional scabies].
AB  - We describe an outbreak of scabies affecting 13 patients and staff members in a
      geriatric ward. The difficulties of diagnosis and treatment are discussed, and it
      is suggested that the local hygiene unit should be involved immediately if
      institutional scabies is suspected.

PMID- 12051052
TI  - [Health promotion and prevention in psychiatry--a Danish perspective].

PMID- 12051053
TI  - [Picture of the month: herpes simplex virus 1 infection].

PMID- 12051054
TI  - [Schiotz's tonometer, a possible source of transmission of prion disease].

PMID- 12051055
TI  - [Prion diseases in general practice--where are the authorities?].

PMID- 12051056
TI  - [Adverse effects of obstetrical epidural block].

PMID- 12051057
TI  - [Coffee and diabetes--something to be really concerned about?].

PMID- 12051058
TI  - [Depressive patients who don't recover].
AB  - Three patients, two men aged 43 and 53 years, respectively, and one woman aged 40
      years, remained depressed despite years of medicinal therapy and counselling,
      although some improvement was eventually achieved in the woman. Although in
      general, depression can be treated successfully, in clinical practice many
      patients experience only limited improvement. It is important to follow through
      all the steps of the guidelines for treatment of depression and to continue
      psychiatric management and care in these kind of situations.

PMID- 12051059
TI  - [Universal vaccination against group C meningococci and pneumococci; advice from
      the Health Council of the Netherlands].
AB  - A committee of the Health Council of the Netherlands recently advised the
      Minister of Health on nationwide vaccination against group-C meningococci and
      pneumococci. They recommended the introduction of both vaccines into the national
      vaccination programme. The meningococcal C vaccine should be introduced as soon
      as possible, and the pneumococcal vaccine should be introduced as soon as a
      combined vaccine against diphtheria, tetanus, pertussis and polio and H.
      influenzae type B is available. In the meantime, due to various clusters of
      meningococcal disease caused by Neisseria meningitidis C in the Netherlands,
      parents have started to have their children vaccinated by buying vaccines and
      asking their general practitioners to perform the vaccination. This unfavourable
      situation must be controlled by the government through clear publicity to parents
      and healthcare workers.

PMID- 12051060
TI  - [The treatment of hypomagnesemia].
AB  - Hypomagnesemia is seen in 11% of the normal hospital population and in up to 65%
      of severely ill patients, and can have many causes. The clinical picture may
      comprise the signs of Chvostek and Trousseau, paraesthesias, tremor and
      convulsions, although asymptomatic hypomagnesemia is seen most often.
      Hypomagnesemia can be treated by parenteral or oral administration of magnesium,
      guided by the serum magnesium level. Parenteral magnesium suppletion is indicated
      if the concentration is below 0.5 mmol/l or in the presence of symptoms of
      hypomagnesemia. In patients with magnesium concentrations between 0.5 and 0.7
      mmol/l and a deficient diet or malabsorption, prolonged therapy is sometimes
      necessary. In such cases, oral Mg-containing antacids in a normal dosage regimen
      may be a good choice, but clinical proof is still lacking. In case of renal
      insufficiency or constipation the magnesium dose should be lowered, while in
      hypophosphatemia oral antacids are contra-indicated.

PMID- 12051061
TI  - [Universal vaccination against group-C meningococci and pneumococci; summary of
      the advice from the Health Counsil of the Netherlands].
AB  - The Health Council of the Netherlands (Gezondheidsraad) assessed the vaccination
      of infants against both group-C meningococci and pneumococci in terms of general
      criteria and basic principles for inclusion in the national vaccination
      programme. Vaccination against meningococci C in the Netherlands is expected to
      prevent about 300 cases of meningococcal disease (meningitis or sepsis), 22
      deaths and 12 cases of severe lasting problems (neurological problems or
      amputations) per year. Vaccination against pneumococci may prevent about 100
      cases of meningitis or sepsis, 3200 cases of pneumonia, 36,000 cases of acute
      otitis media, 11 deaths, 11 cases of severe permanent damage (neurological
      problems, deafness) per year. The Health Council advised implementing vaccination
      against group-C meningococci as soon as possible, through 2 injections at the
      ages of 5 and 6 months or through 1 injection shortly after the child's first
      birthday, and to carry out a catch-up programme for all children and adolescents
      up to and including 18 years of age. The council also advised starting a
      vaccination programme against pneumococci, at ages 2, 3 and 4 months, as soon as
      the current vaccinations against diphtheria, tetanus, pertussis and polio and
      against Haemophilus influenzae type b are combined into 1 injection (in 2002 or
      2003). In view of the concentration of pneumococci disease in the first years of
      life, a catch-up programme is not indicated in this case. The Health Council
      emphasised the importance of microbiological and clinical monitoring of potential
      adverse effects and of public education programmes. The cost of vaccination
      against group-C meningococci is comparable to that of other accepted programmes
      for primary prevention. Compared to other programmes and at the current vaccine
      price, the cost of vaccination against pneumococci is high.

PMID- 12051062
TI  - [Diagnostic image (89). A woman with dysphagia. Dysphagia lusoria].
AB  - In a 49-year-old woman with dysphagia diagnostic endoscopy revealed a mass
      directly dorsal to the esophagus. CT showed an aberrant right subclavian artery
      being the cause of her swallowing problem: dysphagia lusoria.

PMID- 12051063
TI  - [Negative sentinel node in breast cancer patients a good indicator for continued
      absence of axillary metastases].
AB  - OBJECTIVE: To determine the prevalence of axillary recurrences in sentinel-node
      negative patients with breast cancer who had no axillary dissection. DESIGN:
      Follow-up study. METHOD: The first one hundred consecutive sentinel-node-negative
      patients with a minimal follow-up of 36 months (median 47) were included in this
      study. All patients underwent sentinel-node biopsy using the triple technique.
      During the first year after the operation patients were seen on a 3-monthly basis
      and thereafter every 6 months. RESULTS: Intensive pathological examination of the
      harvested sentinel nodes revealed no (micro)metastases in any patient. One
      patient developed an axillary recurrence after 24 months. Three out of the 100
      patients developed distant metastases during follow-up; 2 of them died as a
      result of these metastases. One patient was treated for a local mammary
      recurrence. In terms of survival the sentinel-node procedure did not appear to be
      disadvantageous: the 3-year survival rate in our study was 98% for node-negative
      patients, compared to 88-94% quoted in the literature for node-negative patients
      after axillary dissection. This apparent improvement may be due to better staging
      of breast-cancer patients through the use of the sentinel-node procedure (stage
      migration). CONCLUSION: The triple technique was a reliable method for
      identifying the sentinel node in breast-cancer patients. Compared to the
      historical data on node-negative breast cancer, the sentinel-node procedure
      improved the prognosis of node-negative breast-cancer patients. This effect was
      probably due to the more accurate staging of breast-cancer patients using the
      sentinel-node procedure.

PMID- 12051065
TI  - [Ketoacidosis after cessation of chronic alcohol consumption].
AB  - A 52-year-old man was admitted with diarrhea, near dehydration and dyspnoea.
      After many years of alcohol consumption, he had stopped drinking alcohol over a
      very short space of time and had eaten very little or nothing. He had tachypnoea,
      hypotension and an enlarged liver. Laboratory analysis revealed metabolic
      acidosis with an elevated anion gap, ketone bodies in the urine, increased free
      fatty acid levels and beta-hydroxybutyrate in the serum, fitting the picture of
      alcoholic ketoacidosis. The syndrome is explained by metabolic changes induced by
      chronic alcohol consumption and ketogenesis as the result of fasting and
      dehydration. Treatment consisted of correction of the fluid deficit and
      administration of glucose, after which the patient made a rapid recovery.

PMID- 12051064
TI  - [Prevalence and incidence of depression in residential homes for the elderly in
      the province of Drenthe, the Netherlands: higher than among the elderly in the
      general population, yet lower than in other residential homes].
AB  - OBJECTIVE: To determine the prevalence and incidence of major and minor
      depression in residential homes for the elderly in Drenthe, the Netherlands.
      DESIGN: Cross-sectional and longitudinal study. METHOD: In eleven residential
      homes for the elderly in Drenthe, the point-prevalence rate of depressive
      disorders was determined at baseline (n = 479; mean age = 85 yrs). From the
      baseline-sample, 295 non-depressed subjects were available to estimate the
      incidence rate after six months. The diagnostic procedure consisted of two steps.
      Firstly, all of the subjects were screened for depression using the 'Geriatric
      depression scale'. In the second step, those with a score > 10 were interviewed
      using the 'Schedules for clinical assessment in neuropsychiatry' (SCAN) to assess
      whether there were depressive disorders according to DSM IV criteria. RESULTS:
      The prevalence of major depression was 4.1% (95% CI: 2.3-5.9) and the same rate
      was found for minor depression. The 6-month incidence of major and minor
      depression combined was 2.1% (95% CI: 0.5-3.7). CONCLUSION: The prevalence rate
      for depressive disorders obtained in our study, was twice as high as reported for
      the advanced elderly in the general population, whereas the rates were lower than
      those usually found in residential homes.

PMID- 12051066
TI  - [Fitz-Hugh-Curtis syndrome: 2 patients with perihepatitis and sepsis].
AB  - Two women aged 53 and 22 years presented with abdominal pain and signs of sepsis
      with metabolic acidosis. The first patient had ecchymoses all over her body, the
      second patient had an enlarged left kidney with wedge-shaped hypo-intense areas
      on the CT scan. The clinical condition of both women deteriorated. On laparoscopy
      perihepatitis with fibrin wires ('violin strings') was seen, pathognomonic for
      Fitz-Hugh-Curtis syndrome. Upon appropriate antibiotic treatment, both patients
      fully recovered. Although it is common belief that Fitz-Hugh-Curtis syndrome is
      caused by local spread from the fallopian tubes into the peritoneal cavity, these
      presentations suggest a haematogenous spread of Neisseria gonorrhoeae as well as
      Chlamydia trachomatis in the first case, and C. trachomatis in the second case.

PMID- 12051067
TI  - [Less feeling of life and a sinus pattern of the cardiogram: 2 alarm signals].

PMID- 12051068
TI  - [Diagnostic image (80). A man with thirst and polyuria].

PMID- 12051069
TI  - [Psychosis during and after disulfiram use].

PMID- 12051070
TI  - [Physical diagnosis--rectum toucher].

PMID- 12051071
TI  - [Lasers in dentistry 3. The use of lasers for the prevention of dental caries].
AB  - Studies in our laboratories have demonstrated that specifically chosen CO2 laser
      treatment of dental enamel can markedly inhibit subsequent caries-like
      progression compared to controls in a laboratory model. Optimum caries inhibition
      in enamel appears to be achieved by pretreatments that produce surface
      temperatures in the range of 800-1200 degrees C. For clinical application the
      surface enamel heating must not lead to consequent pulp chamber temperature rises
      of > 4 degrees C. To meet these conditions a pulsed laser is required with a
      sufficiently high absorption coefficient (wavelength = 9.3 or 9.6 microns), pulse
      duration of 5-100 microseconds, 10-25 pulses per spot, repetition rate of 10-30
      pulses per second, and low but effective fluence (approximately 1-5 J/cm2/pulse).
      A human intra-oral study has confirmed inhibition of caries progression in the
      human mouth. The clinical potential is good for caries preventive treatments by
      specific carbon dioxide laser conditions.

PMID- 12051072
TI  - [Design of custom-shaped abutments for single-tooth crowns on implants].
AB  - Single-tooth implants have become a predictable treatment option. Acceptable
      esthetics are an important factor for success. The emergence profile of the crown
      in the cervical region is complicated by the discrepancy between the round shape
      and the small diameter of the implant and the desired anatomical shape of the
      crown. An abutment on an implant has to provide this natural looking emergence
      profile and has to support the crown. Custom-shaped abutments are the best option
      for this task. Many items influence the design. This article discusses a set of
      guidelines for the design of custom-shaped abutments for single-tooth implants.

PMID- 12051073
TI  - [Orthodontic-surgical treatment of patients with mandibular hypoplasia].
AB  - A combined orthodontic-surgical treatment strategy for patients with mandibular
      hypoplasia is presented. The importance of a proper diagnosis on which the
      treatment should be based is emphasised. The principles of the orthodontic pre
      and postoperative treatment and the surgery are explained. The possibility to use
      the curve of Spee to gain vertical chin height is emphasised. This can be
      achieved by levelling of this curve postoperatively. Possible unfavourable side
      effects are mentioned. It is concluded that highly predictable results can be
      achieved using the described techniques.

PMID- 12051074
TI  - [Tissue engineering].
AB  - Tissue engineering is a fast developing multidisciplinary field. Both from a
      medical and social point of view, there is great need to safe tissues and organs
      to overcome the shortage of donor organs and to reduce the health care cost. At
      the same time, progress made in the field of molecular sciences as well as in
      biomaterials and chemical engineering, offers great possibilities to manipulate
      cells, growth factors and carrier materials in such a way that growth of tissues
      can be achieved.

PMID- 12051075
TI  - [Oral manifestation of Crohn disease].

PMID- 12051076
TI  - [Cystitis and urethritis].

PMID- 12051077
TI  - [Multi-slice CT of aortocoronary venous bypasses and mammary artery bypasses:
      evaluation of bypasses and their anastomoses].
AB  - OBJECTIVE: To assess aortocoronary grafts and internal mammary artery bypasses by
      means of EKG-triggered contrast-enhanced multi-slice spiral CT, and to evaluate
      the diagnostic accuracy of this new imaging modality. MATERIAL AND METHODS: 59
      patients with up to 5 aortocoronary grafts and/or internal mammary artery
      bypasses per patient were examined with regard to bypass morphology, the free
      passage, and the proximal as well as the distal anastomoses using multislice
      computed tomography. Axial source images were calculated by means of
      retrospective triggering at different diastolic delay times, and were
      postprocessed in several planes with the multiplanar volume reconstruction (MPVR)
      software. RESULTS: On the pre-condition that data sets were acquired at sinus
      rhythm and at a heart rate lower than 65/min, aortocoronary grafts and internal
      mammary artery bypasses could be depicted in adequate diagnostic quality in about
      80% of all cases with contrast-enhanced multi-slice spiral CT. Both, the free
      passage of the bypasses as well as the morphology of the proximal anastomoses
      were sufficiently assessed with multiplanar volume reconstruction (MPVR), whereas
      the distal anastomoses couldn't be depicted sufficiently in 20% of all cases.
      CONCLUSION: As a non-invasive method, contrast-enhanced and ECG-triggered multi
      slice spiral computed tomography has gained diagnostic potential for the accurate
      visualization of aortocoronary grafts and the internal mammary artery bypasses.

PMID- 12051078
TI  - [Quantitative determination of coronary vascular calcinosis (coronary calcium
      score) with double-helical CT].
AB  - Coronary heart disease is a common disease, with the typical characteristic of
      coronary sclerosis, an abnormal calcification of the heart's blood vessels. The
      amount of coronary calcification is in direct correlation to the extent of
      coronary heart disease. With the double-detector-helical-CT it is possible to
      detect and quantify these calcifications. The correlation of the "Calcium
      Scoring" with the results of coronary-angiography, myocardial scintigraphy and
      clinical findings shows the value of this method of coronary heart diagnostic.
      False negative results, based on low calcified fatty stenotic plaques and false
      positive results, based on high calcificated plaques without significant stenosis
      should be taken into account.

PMID- 12051079
TI  - [Virtual colonoscopy with multi-detector computerized tomography].

PMID- 12051080
TI  - [BALTOMA--long-term follow-up].
AB  - PURPOSE: The purpose of this work was to describe the findings and the long term
      follow up of pathologically confirmed bronchus-associated lymphoid tissue
      lymphoma (BALTOMA) in 6 patients. METHODS: CT examinations and conventional
      radiological examinations were reviewed and compared to describe typical
      radiological findings and patterns of pulmonary manifestations. It were described
      the number of lesions and characteristics like presence of airspace
      consolidation, ground-glass attenuation, bubble-like radiolucencies, air
      bronchogram, bronchial dilatation, Infiltration and the long term behaviour of
      the manifestations. RESULTS: Lesions with a positive air bronchogram, no
      infiltration of extrapulmonary tissue or extrapulmonary manifestations were
      revealed as typical findings. Only a slow or no progression of disease was shown
      in most patients over a term of up to twelve years. CONCLUSIONS: The lymphoma of
      the bronchus-associated lymphoid tissue of the lung is a rare tumor. A positive
      air bronchogram, a multiplicity of disease, bilateral lesions, a fibrotic
      transformation of the lung tissue and no growth or only a slow groth over al long
      term of observation are typical radiological findings.

PMID- 12051081
TI  - [Use of computer-assisted diagnosis (CAD) and tele-mammography in preventive
      breast cancer screening].

PMID- 12051082
TI  - The sentinel lymph node biopsy in breast cancer.
AB  - OBJECTIVE: To evaluate the possibility and accuracy of this new diagnostic
      approach to the breast cancer disease in our centre. MATERIAL AND METHODS: Since
      March 1999, every patient presenting with a cT1-T2 N0 breast carcinoma was
      scheduled for a sentinel lymph node search. An injection of Tc-99 labelled
      nanocolloid with a dose of 1 mCu was injected either intramammary or
      intradermally. The patients have been divided into two groups: in group I, they
      received their injection intramammarily the day before the operation; because of
      several failures in identifying the sentinel lymph node (SLN), the protocol was
      modified, the patients receiving their injection the day of operation,
      intradermally (group II). Once a lymphoscintigraphy done, the SLN was identified
      at operation using a detection probe, after the primary tumour had been removed.
      A routine axillary dissection was then performed to remove the rest of the lymph
      nodes. All the nodes were then checked routinely for metastatic cells. The SLN
      was also screened by semi-serial slides and by immuno-assay. RESULTS: From March
      1999 till March 2001, sixty patients presented consecutively with a T1 or T2
      biopsy proven breast carcinoma with no clinical lymph nodes. They were all
      scheduled for a sentinel lymph node search according to the protocol. Mean tumour
      size was 9.9 mm (ranging from 4 to 23 mm). Fourteen patients (group I) received
      their injection intramammarily but we failed to identify the sentinel node in
      five patients (35%). The remaining forty-two patients (group II) received their
      injection intradermally. Sentinel nodes were then identified in forty-three
      patients (93%). Positive SLN were discovered in eleven cases by routine
      examination (13 positive nodes among 104 harvested sentinel nodes, i.e. 13%).
      Micro metastases were discovered in three other SLN by immunohistology. In total,
      605 lymph nodes were evaluated through the axillary dissection, representing a
      mean number of 10.08 lymph nodes per patient. For four patients, positive lymph
      node were discovered in the axillary dissection while SLN were negative (6.6% of
      false negative). CONCLUSIONS: During this learning curve period, it appears that
      the method for screening the SLN is reliable, since the figures encountered are
      similar to those of the literature. By adding a perioperative blue dye injection,
      it might be possible to reduce the percentage of false negative results. It is
      difficult to assess, at present, the impact SLN could have on survival.

PMID- 12051083
TI  - Primary psoas abscess. Report of three cases.
AB  - BACKGROUND: Primary psoas abscesses are a rare clinical entity with subtle and
      non specific symptoms, most commonly seen in patients predisposed to infections.
      Early diagnosis and appropriate management are therefore challenging aspects for
      physicians. PATIENTS AND METHODS: We present three patients with primary pyogenic
      psoas abscess, treated at the Heraklion University Hospital, during a 5-year
      period. The two male and one female patient, aged 36-51 years were admitted with
      fever, abdominal pain and a palpable tender mass. RESULTS: The classical sign of
      limping was absent in all cases. Positive psoas symptoms were detected in only
      two patients. CT scan accurately confirmed the diagnosis in all cases. The
      patients were successfully treated with antibiotics and prolonged surgical
      drainage. Staphylococcus aureus was the causative microorganism in the first two
      and Bacteroides fragilis in the third patient. This is the first reported case
      resulting from this specific bacteria. None of our patients had any predisposing
      risk factor. CONCLUSIONS: A high index of suspicion is mandatory to enable early
      recognition of this rare clinical disease. CT scan is the standard diagnostic
      tool to confirm diagnosis. Prolonged drainage and appropriate antibiotics are
      essential for the successful treatment of primary psoas abscesses.

PMID- 12051084
TI  - Tuberculous lymphadenopathy in adults: a review of 35 cases.
AB  - We retrospectively reviewed clinical, diagnostic, therapeutic and prognostic
      features of 35 patients (25 female, 10 male, mean age: 33 years, range: 16-70)
      with tuberculous lymphadenopathy (TB LAP) which had been followed since 1980. The
      diagnosis was established by tissue sampling in 32 cases (caseating granulomatous
      adenitis in 89%) or presence of acid-fast bacilli (AFB) in the aspirate in 2
      cases and in the drainage in 1 case. Paraffin-embedded granulomatous tissues were
      stained by Ehrlich-Ziehl-Neelsen (EZN) and also Mycobacterium tuberculosis DNA
      was studied by polymerase chain reaction (PCR) (n = 21). The patients were
      admitted with enlarging LAP (34%), draining LAP (9%), and both systemic
      complaints and enlarging LAP (57%). Cervical lymph nodes were the most frequently
      involved site (77%). Pathologic findings on chest X-ray were seen in 23%.
      Erythrocyte sedimentation rate (ESR) was higher than 100 mm/hour in 25% and
      associated with systemic complaints. Tuberculin skin test was positive in 91%.
      AFB could not be seen in any granulomatous tissue (n: 21), but PCR study was
      positive in 33% (7/21). All patients were given anti-TB treatment (INH,RMP,EMB
      and/or PZA). Surgical excision of draining LAP with surrounding inflammatory
      tissues in addition to the medical treatment was needed in 2 cases. Clinical
      improvement was obtained within 3 months of the treatment and ESR returned to
      normal within 5 months. After completion of the treatment, 22 patients were
      followed-up; mean duration was 3 years, and none relapsed. In conclusion, a
      patient with TB LAP generally presents with a few small, painless, cervical lymph
      nodes, which are slowly enlarging. For exact diagnosis, excisional biopsy for
      histologic and microbiologic studies is essential. Use of anti-TB drugs is the
      main therapeutic option.

PMID- 12051085
TI  - Serum progesterone levels in patients with gastric and colorectal cancers.
AB  - BACKGROUND: It is known that various malignant tissues possess progesterone
      receptors. It has been reported that the serum progesterone levels increase and
      show a prognostic significance in gastric carcinoma. We carried out a study to
      determine the serum progesterone level in gastric cancer, and colorectal cancer.
      METHODS: 140 of our patients were male and 56 female. We determined serum
      progesterone level in patients with gastric cancer, and colorectal cancer.
      Patients with benign diseases participated in the study as control group.
      RESULTS: In male patients with gastric cancer (n = 90) and colorectal cancer (n =
      50) the serum progesterone level was not significantly higher than in the control
      group (n = 80) (mean: 1.08 +/- 0.73, 1.08 +/- 0.32 and 1.01 +/- 0.38 ng/ml,
      respectively). Among the female patients with gastric cancer (n = 26) and
      colorectal cancer (n = 30), the serum progesterone level was also not
      significantly higher than in the control group (n = 30) (mean: 1.19 +/- 0.77,
      1.21 +/- 0.72 and 1.12 +/- 0.61 respectively). In males, the sensitivity of
      progesterone for gastric cancer was 55.5% and 64% for colorectal cancer with a
      specificity of 37.5%. In females, the sensitivity of progesterone for gastric
      cancer was 54% and 57% for colorectal patients with a specificity of 40%.
      CONCLUSIONS: Serum progesterone level does not correlate with the presence or
      absence of gastric cancer or colorectal cancer, and it is not a useful tumour
      marker.

PMID- 12051086
TI  - Successful replantation following an accidental forearm amputation. Case report
      and review of the literature.
AB  - We report a patient who suffered an accidental complete amputation of the right
      forearm followed by a successful replantation and comment on the indications and
      management of macro-replantations of the upper limbs. This is the first time that
      a successful surgical procedure of this nature has been performed in Bolivia,
      with no post-operative complications and excellent long-term functional recovery.

PMID- 12051087
TI  - Video-assisted Port-Access surgery for radical myxoma resection.
AB  - The curative treatment of choice for myxomas is surgical removal. Most of the
      patients are young and active and are focused on postoperative comfort, cosmesis
      and a fast track to complete rehabilitation, all of which is related to the
      degree of invasiveness of the intervention. We report our first experience with
      video-assisted Port-Access surgery for atrial myxoma. From February 1997 until
      April 2000, nine patients (3M/6F)) had an atrial myxoma resection with the
      Heartport Endo-CPB and Endo-aortic clamp system. Mean age was 54 +/- 21.9 years.
      Most of the patients were symptomatic and had good LV function. Two patients had
      a combined procedure: one mitral valve replacement and one vascular shunt for
      dialysis. Mean aortic cross clamp time was 69 +/- 32.8 min and mean perfusion
      time was 103 +/- 42.7 min. There were no conversions to sternotomy. Three
      patients had minor complications. Mean ICU and hospital stay were 1 +/- 1.4 and 6
      +/- 3.9 days respectively. No thromboembolic or peripheral ischaemic
      complications were observed. There were no hospital deaths. No recurrent tumors
      have been identified. The Port-Access approach for myxoma resection constitutes a
      invaluable alternative to sternotomy with the same gold standards of results and
      quality.

PMID- 12051088
TI  - Lethal cutaneous verrucous carcinoma.
AB  - Verrucous carcinoma is a rare subtype of well-differentiated squamous cell
      carcinoma that may occur anywhere on the skin. It is slow growing, enlarging
      relentlessly and invading locally. Some cases were reported to occur on chronic
      scar tissue but demonstrated the same clinical course than in other locations.
      Herein, we report on a very unusual case of cutaneous verrucous carcinoma arisen
      from a long-standing (40 years old) burn scar and which involved the pleura five
      years after the initial surgical resection. To our best knowledge, this is the
      first case of pleural involvement by a verrucous carcinoma originating from the
      skin.

PMID- 12051090
TI  - Spontaneous rupture of a Dacron prosthesis.
AB  - This case report concerns a spontaneous rupture of a Dacron prosthesis 19 years
      after its insertion. The rupture occurRed in the mid-graft portion, remote from
      the anastomoses and was not associated with proved infection. It was the result
      of an intrinsic deterioration of the graft textile structure. The patient
      recovered after insertion of a new Dacron graft. The authors discuss the
      incidence of graft degeneration and the causative factors. Lesions on the frame
      of the graft could be due to a variety of factors such as intrinsic Dacron graft
      factors, manufacturing, inappropriate utilization, physical, enzymatic or
      immunological factors.

PMID- 12051089
TI  - Basal cell carcinoma of the external auditory canal.
AB  - Carcinomas of the external auditory canal are rare, nevertheless they are
      associated with a relatively poor prognosis. Among these tumours, basal cell
      carcinomas are less frequent than squamous cell carcinomas. Anyway, it is
      difficult to determine if their prognosis is better, as in other localizations on
      the body. We reviewed six patients, presenting locally advanced basal cell
      carcinomas of the external auditory canal and considered the history of their
      disease, the treatment procedures and final oncological outcome. Four of the
      patients died of the disease within five years from surgery. They presented local
      recurrences even after radical surgical excision in free tissue margins. From
      these findings we have the impression that basal cell carcinoma of the external
      auditory canal behave, even after radical surgery, as an aggressive tumour
      associated with a really poor prognosis.

PMID- 12051091
TI  - Surgery from former eastern Europe.

PMID- 12051092
TI  - The cybergut. An experimental study on permanent microchip neuromodulation for
      control of gut function.
AB  - Acute electrical stimulation of vagal nerve changes gut motility, secretion as
      well as absorption, and it may have effect on food intake and satiety regulation.
      The aim of the study was to evaluate the effect of permanent microchip mediated
      neuromodulation (McNm) of vagal afferent activity on GI function and body mass in
      the experimental model. MATERIAL AND METHODS: Two-steps study was performed. In
      the first step (evaluation of food intake) 16 rabbits were divided in two groups,
      8 animals each. Group A was subjected to microchip mediated neuromodulation
      (McNm), and control group B was sham operated. In both groups laparotomy and
      vagal exploration were performed. In the second step pathomechanism of Mc action
      was analysed in fourteen Wistar rats divided in two groups (C and D), 7 animals
      each. Group C was subjected to Mc implantation and gastrostomy placement and
      group D (controls) to gastrostomy placement alone. RESULTS: Food intake and body
      mass significantly decreased in group A after Mc implantation compared with the
      preoperative period and control group B. No differences were found in the
      frequency of gastric contractions between groups C and D, however, their
      amplitude was significantly stronger in group C. Neuromodulation had significant
      effect on BAO without changes in MAO levels. CONCLUSIONS: Low frequency permanent
      vagal neuromodulation affects gastric function and influences food intake in the
      experimental model.

PMID- 12051093
TI  - Clinical significance of increased intraabdominal pressure in severe acute
      pancreatitis.
AB  - The aim of the study was to assess whether increased intra-abdominal pressure
      affects the clinical course and reflects on the effectiveness of the conservative
      treatment in patients with severe acute pancreatitis. Data on 37 consecutive
      patients with severe acute pancreatitis that were collected prospectively
      included APACHE II score, daily measurement of the intra-abdominal pressure, and
      clinical routine. Group A consisted of 26 patients with intra-abdominal pressure
      < 25 cm/H2O during their treatment period, and group B consisted of 11 patients
      with intraabdominal pressure > or = 25 cm/H2O. SIRS, MODS, complication rate and
      mortality were analysed. The age, APACHE II scores and hospital stay were similar
      in both groups. ICU stay was 9.1 +/- 9.6 vs. 20.7 +/- 16.8 days in groups A and
      B, p < 0.05. SIRS and MODS developed less frequently in group A. More pulmonary
      complications developed in group B, reaching 64% compared to 19% in group A, p <
      0.05. Intra-abdominal pressure had negative interrelation with enterally provided
      volume (r = -0.45, p < 0.001) and positive interrelation with parenterally
      provided volume (r = +0.27, p < 0.01) in all. Mortality was zero in group A vs.
      36% in group B, p < 0.01. Increase of the intra-abdominal pressure is common
      during the clinical course of severe acute pancreatitis and can be associated
      with aggressive fluid replacement therapy. Routine measurement of the intra
      abdominal pressure is rational in the clinical setting of the ICU and gives
      additional criteria for the evaluation of the clinical course and the
      effectiveness of the treatment. Marked increase of the intra-abdominal pressure
      should be considered a serious prognostic sign in patients with severe acute
      pancreatitis.

PMID- 12051094
TI  - Bacterial translocation as a cause for septic complications in obstructive
      colonic ileus.
AB  - Failure of intestinal barrier function and subsequent translocation of
      microorganisms and their degradation products play a decisive role in development
      of systemic septic complications for many systemic and intra-abdominal
      pathologies, for example, following obstructive colonic ileus (OCI). This study
      was aimed at the evaluation of the intestinal barrier state in OCI. Sixty albino
      Wistar rats weighting 250 to 300 g (mean 265 g) were divided into four groups (15
      animals in each). Acute colonic ileus (ACI) was modeled as follows except a
      control group (Group 1). Our objective was to examine changes in bacterial flora
      in the abdomen, mesenteric lymphatic nodes (MLN), liver, spleen, and lungs during
      the model of OCI after 72 hours following the beginning of experiment. The
      composition of parietal mucus in normal and in OCI 48 hours following the
      beginning of experiment examined. Interleukin (IL-VI) levels were determined in
      both portal and peripheral blood. The right-hand half of colon was ligated at the
      level of ileocaecal junction in animals of Group 2 (n = 15), whereas in animals
      of Group 3 (n = 15) it was ligated at the level of sigmoid colon. With the same
      purpose, a portion of the suspended caecal content was administered into lumen of
      the jejunum at a concentration of 10(6) colony-forming units (CFU) in animals of
      Group 4 (n = 15). Experimentally--induced OCI causes significant bacterial
      translocation (BT) in rats. The process of colonization of the proximal small
      intestine with colonic flora takes place under the conditions of ileus. The
      conditions favorable for the development of BT are generated with colonization of
      10(6) CFU in volume. As a result, intestinal flora penetrates into the abdominal
      organs and lungs. Its highest concentrations are noted in the lymph nodes, lungs
      and liver. The modeling of the small intestine colonization with colonic flora
      (Group 4) demonstrates critical parameters of microbial semination.

PMID- 12051095
TI  - Does extended lymphadenectomy improve survival of pancreatic cancer patients?
AB  - PURPOSE: Aim of the study was to assess the value of extended lymphadenectomy for
      pancreatic cancer. MATERIALS AND METHODS: A retrospective analysis of 201
      patients with pancreatic and ampullary cancer who underwent pancreatectomy with
      standard or extended lymph node dissection were analysed in order to compare the
      rate of perioperative complications and 5-year survival. RESULTS: Of 201 patients
      treated, 65 (32%) underwent standard (group I) and 136 (68%) extended (group II)
      lymphadenectomy. These two groups were similar with regard to age, gender, tumour
      location, advancement and radicality of performed resection. The mean operating
      time in the extended lymphadenectomy group was longer (383 +/- 81 min) compared
      to the standard group (357 +/- 64 min) but observed difference was insignificant.
      Similarly, there were no significant differences with respect to transfused blood
      and plasma units. The mean number of resected lymph nodes was significantly (p <
      0.001) higher in group II (29.0 +/- 17.7) compared to group I (13.0 +/- 7.4). The
      overall morbidity and mortality rates were 43% and 6.9%, respectively without
      significant differences between both groups. The overall 5-year survival for
      pancreatic and ampullary cancer was 16.7% and 67.6% respectively, and was similar
      regardless the type of performed lymphadenectomy. Patients with node-negative
      pancreatic cancer following extended lymphadenectomy had significantly higher (p
      < 0.01) 5-year survival (48%) compared to the standard resection (22%).
      CONCLUSIONS: Extended lymphadenectomy can be performed with similar morbidity and
      mortality rates compared to the standard resection. Benefits of 5-year survival
      can be achieved only in a limited group of patients with non-advanced pancreatic
      cancer.

PMID- 12051096
TI  - Perspectives in sequential pneumatic compression of the lower extremities (SCD)
      for laparoscopic surgery.
AB  - During most cases of laparoscopic surgery, a pneumoperitoneum of 12-14 mm Hg CO2
      is established. Although not always detected in healthy patients, a
      pneumoperitoneum will cause clinically relevant pathophysiological changes. Among
      other side effects, a pneumoperitoneum will alter the venous blood return from
      the lower extremities and depress cardiac function. Results from experimental and
      clinical studies concerning the influence of a pneumoperitoneum on venous blood
      return and cardiac function are reviewed and a simple model of cardiac function
      impairment during laparoscopic surgery with a pneumoperitoneum is presented.
      Sequential pneumatic compression of the lower extremities is effective in
      reducing venous stasis during and after conventional surgery. Several clinical
      trials determined the hemodynamic effect of intraoperative SCD (sequential
      compression device) during laparoscopic surgery. In the following text the
      results of these studies are summarized and possible implications for the
      clinical use of SCD in laparoscopic surgery are discussed. Although potential
      benefits of SCD-therapy have been shown only in studies of low methodological
      quality, intraoperative SCD-therapy is recommended during prolonged laparoscopic
      surgery.

PMID- 12051097
TI  - Pedal artery imaging using DSA, CE-MRA and duplex.
AB  - Diabetic macroangiopathy is associated with a typical disease pattern, mostly
      affecting the tibial but sparing the pedal arteries. Bypass grafts to these
      patent pedal vessels have evolved into a feasible technique. Restoring a palpable
      pulse in the ischemic foot they create the prerequisite to heal an ulcer or
      gangrene. Preoperative evaluation of pedal arteries demands a detailed depiction
      of the entire pedal vascular system. At present, the main options for
      preoperative pedal artery imaging are selective DSA contrast enhanced MRA and
      Duplex ultrasound. The aim of this review article is to give a survey of these
      three techniques and to determine their potential to depict pedal run off
      vessels. Selective DSA is still the standard diagnostic tool in preoperative
      pedal artery imaging. CE MRA offers high contrast related resolution but in-plane
      resolution is inferior to the concurrent imaging techniques. Duplex is the
      preferable method to evaluate a pedal artery's diameter and morphology. Both, CE
      MRA and Duplex are worthwhile additional imaging techniques in case DSA did not
      sufficiently depict the pedal vasculature.

PMID- 12051098
TI  - New challenges in the treatment of early breast cancer or surgery for early
      breast cancer ... can less be more?
AB  - Breast cancer is a major public health problem of great interest and importance
      to physicians in a variety of specialities. The incidence of the disease has
      increased dramatically, heightening concern among physicians and women in
      general. In addition, long-term results are now available from clinical trials
      initiated in the 1970s and 1980s to evaluate the usefulness of early detection
      with mammography and physical examination, breast-conserving treatment with
      limited breast surgery and irradiation, and adjuvant systemic therapy with
      hormonal therapy and chemotherapy. Furthermore, in the light of newly gained
      knowledge, new strategies for addressing this problems have been proposed. In
      this review, we will summarize the evidence evaluating the strategies for
      diagnosis and therapy initiated in the 1970s and 1980s, and will describe the
      prospects for prevention and for more specific treatments bases on evolving
      biologic knowledge. Our review will only focus on early breast cancer, discussing
      the following topics: Breast Cancer screening: Who should be screened and how
      often?; New technologies in Breast Cancer Diagnosis; Selection of patients for
      Breast-conserving therapy; Management of the axilla in primary breast cancer or
      "Is sentinel lymph node biopsy useful?"; Expanded use of adjuvant systemic
      therapy; Genetic predisposition for Breast Cancer; Clinical options for Women at
      high-risk for Breast Cancer.

PMID- 12051099
TI  - ALSO Australia: a collaborative approach to promoting safe maternity care.

PMID- 12051100
TI  - Nurses. Worth looking after.

PMID- 12051101
TI  - Zero tolerance to violence--a right at work.

PMID- 12051102
TI  - When will they get the message?

PMID- 12051103
TI  - New classification structure and rates of pay for nurses in aged care.

PMID- 12051104
TI  - A scent of a woman.

PMID- 12051105
TI  - Raloxifene and cardiovascular disease.

PMID- 12051106
TI  - Pheromones, sexual attractiveness and quality of life in menopausal women.
AB  - Pheromones, and their effects, are reviewed with a special emphasis on their
      potential contribution to sexual attractiveness in the menopause. Key topics
      included are biological functions of pheromones in animals and humans, the source
      of pheromones in humans, the axillary extract studies that led to the independent
      synthesis of pheromones, olfactory mechanisms for mediating pheromones, and
      aging, attractiveness and sexual dysfunction. Physical attractiveness is
      important for a better quality of life. Three separate, double-blind, placebo
      controlled investigations, using the same protocol, all demonstrated that a
      synthesized pheromone, topically applied, increased sexual attractiveness. If
      partners are available, sexual attractiveness can increase affectionate intimate
      behavior, which, in turn, increases well-being and quality of life. More research
      is needed to address ways in which postmenopausal women can benefit from
      pheromones.

PMID- 12051107
TI  - Effects of hormone replacement therapy on cognitive aging and dementia risk in
      postmenopausal women: a review of ongoing large-scale, long-term clinical trials.
AB  - The aim of this review is to discuss the purpose, design, and expected findings
      of several ongoing large-scale, long-term clinical trials studying the effects of
      hormone replacement therapy (HRT) on cognitive aging and risk of developing
      dementia. The Women's Health Initiative Study of Cognitive Aging (WHISCA) and the
      cognitive component of the Women's International Study of long Duration Oestrogen
      after Menopause--Cognition (WISDOM-COG) (to be completed in 2005 and 2006,
      respectively) will provide information about the effects of HRT on cognitive
      aging. The Preventing Postmenopausal Memory Loss and Alzheimer's with Replacement
      Estrogens study (PREPARE), the Women's Health Initiative Memory Study (WHIMS) and
      the dementia component of WISDOM-COG (to be completed in 2003, 2005 and 2009,
      respectively) will address the question of whether estrogens can delay or prevent
      dementia. These ongoing clinical trials will also be the first to study the
      effects of estrogen with and without progesterone, and the effects of HRT in
      women with natural versus surgical menopause, on cognitive aging and risk of
      dementia. Based on the existing literature, we discuss which specific cognitive
      areas are most likely to be affected by HRT. We also raise the issue that the
      type of estrogen agent may affect the outcome of these studies.

PMID- 12051108
TI  - Low-dose hormone replacement therapy: effects on bone.
AB  - Hormone replacement therapy (HRT) is considered the mainstay for postmenopausal
      osteoporosis prevention. However, at the standard doses, HRT preparations can
      induce bothersome hormone-related side-effects, in both sequential and continuous
      combined regimens. Lower-dose HRT schedules are reported to be highly effective
      in the relief of climacteric symptoms, inducing minimal endometrial stimulation
      with very low rates of unscheduled bleeding. Moreover, low-dose HRT associated
      with an adequate calcium supplement can spare bone by preventing the increase in
      bone turnover and the resultant bone loss in postmenopausal women. Low-dose
      regimens may be considered as a starting dose not only in elderly subjects, but
      also in early postmenopausal women to allow for adjustment to HRT. In older
      women, these may minimize the occurrence of side-effects and improve compliance,
      while preventing the long-term consequences of estrogen deprivation.

PMID- 12051109
TI  - Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional
      and longitudinal studies.
AB  - OBJECTIVE: To determine whether hormone replacement therapy (HRT) preserved or
      improved olfactory sensitivity in healthy postmenopausal women. METHODS: Sixty
      two postmenopausal women participated in a cross-sectional study of olfactory
      sensitivity involving detection, intensity discrimination, quality discrimination
      and two measures of quality recognition. In addition, 24 postmenopausal women
      participated in a longitudinal study of olfactory sensitivity. This study allowed
      for the measurement of estrogen effects (while holding practice effects constant)
      and the measurement of practice effects (while holding HRT conditions constant).
      RESULTS: In the cross-sectional study, we were unable to detect any differences
      between those receiving HRT and those not receiving HRT. Duration of exposure to
      HRT was examined by selecting women who had 5 or more years of exposure to their
      HRT regimen. Even after the data were reorganized into those for opposed- and
      unopposed-estrogen use, we were unable to detect any differences. However,
      olfactory threshold increased as a function of increasing age, regardless of HRT
      status. A gradual decrease in ability to detect odors was observed from the 4th
      to the 6th decade, with a greater decrease between the 6th and 7th decades. In
      the longitudinal study, no effects of HRT were detected even when practice
      effects were uncontrolled. Practice effects were assessed both between and within
      subjects. No effects of practice were detected when initial baseline performance
      was used as a covariate. CONCLUSION: Although prophylactic HRT has been suggested
      to be associated with improved olfactory function, we find that its use in
      healthy postmenopausal women does not enhance performance in a wide range of
      olfactory tasks.

PMID- 12051110
TI  - Tamoxifen, hormone receptors and hormone replacement therapy in women previously
      treated for breast cancer: a cohort study.
AB  - OBJECTIVE: To determine the risk of recurrence of breast cancer associated with
      the use of hormone replacement therapy (HRT) in the management of menopausal
      symptoms in women previously treated for breast cancer who were taking concurrent
      tamoxifen or who were estrogen receptor-positive. METHODS: The study group
      comprised 1472 women with histologically confirmed breast cancer, of whom 342
      subjects (23.2%) elected to use hormonal therapy in the management of their
      menopausal symptoms. Women were not excluded from treatment with hormonal therapy
      if they were taking adjuvant tamoxifen or if they had receptor-positive breast
      cancer. The response of these patients was compared with that of the rest of the
      database. A Cox regression analysis was performed with sex hormone usage as time
      dependent covariate. Disease-free interval was the outcome measured. RESULTS:
      Subjects who took concurrent tamoxifen with combined continuous estrogen
      progestogen therapy had a hazard ratio of 0.67 (95% confidence interval (CI) 0.14
      3.24, p = 0.62), while concurrent tamoxifen and topical vaginal estrogen users
      had a hazard ratio of 0.31 (95% CI 0.10-2.57, p = 0.28). The hazard ratio for the
      estrogen-progestogen users who were estrogen receptor-positive was 0.24 (95% CI
      0.10-1.49, p = 0.14). CONCLUSIONS: The use of HRT was not associated with an
      increased risk of recurrence of breast cancer in women taking concurrent
      tamoxifen or who were estrogen receptor-positive.

PMID- 12051111
TI  - Transvaginal color Doppler sonographic evaluation of the uterus in postmenopausal
      women on daily raloxifene therapy.
AB  - OBJECTIVE: To evaluate the effect of raloxifene on the endometrium and the uterus
      by transvaginal color Doppler sonography. METHODS: The study group was composed
      of 34 asymptomatic postmenopausal women. All had been treated with raloxifene 60
      mg/day for 6 months. The patients underwent transvaginal color Doppler sonography
      before starting raloxifene and after treatment. The uterus was scanned by
      transvaginal ultrasound to evaluate the pulsatility (PI) and resistance (RI)
      indices of both uterine arteries. The mean values for the uterine arteries were
      analyzed. RESULTS: The mean age of the women was 57.56 +/- 4.44 years (range 48
      64 years), and mean number of years since the menopause was 8.67 +/- 5.44 (range
      1-25 years). The mean endometrial thickness (3.62 +/- 1.13 vs. 3.59 +/- 0.95 mm)
      and uterine volume (40.67 +/- 18.36 vs. 38.05 +/- 19.47 ml) were not
      significantly different before starting treatment and after treatment (p > 0.05).
      The mean values of the PI (3.49 +/- 1.56 vs. 3.90 +/- 1.38) and RI (0.94 +/- 0.11
      vs. 0.98 +/- 0.10) of the uterine arteries were not significantly different
      before starting treatment and after treatment (p > 0.05). CONCLUSION: Daily
      therapy with raloxifene did not stimulate the endometrium, the uterus or uterine
      blood flow.

PMID- 12051112
TI  - Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal
      women: effects on arterial compliance and endothelial function.
AB  - BACKGROUND: The cardiovascular effects of hormone replacement therapy (HRT) are
      controversial. Improvement in vascular function, potentially mediated, at least
      in part, via improvements in lipid profiles, is a proposed mechanism of estrogen
      action; however, there are few controlled human trials. We have studied the
      effects of HRT, independent of changes in lipid profile, with transdermal
      estrogen therapy, focusing on blood pressure, lipid profiles and vascular
      function, encompassing both biomechanical arterial properties (systemic arterial
      compliance and pulse wave velocity) and endothelial function (flow-mediated
      vasodilatation). METHODS: In this 2-year, double-blind, placebo-controlled, cross
      over study, 34 healthy postmenopausal women were randomized to transdermal
      estrogen alone (Menorest, 50 micrograms) or placebo. After withdrawals, 25 women
      completed measurements at baseline, 6 weeks, 6 months and 12 months during both
      treatment phases. RESULTS: Transdermal estrogen did not improve blood pressure,
      lipid profiles or arterial function, compared with placebo. CONCLUSION: From this
      randomized, controlled trial, it appears that transdermal estrogen alone, in
      healthy postmenopausal women, does not improve lipid profiles or a spectrum of
      indices of arterial function, compared with placebo. These results would suggest
      that there might not be a beneficial effect of transdermal HRT on the vasculature
      in postmenopausal women.

PMID- 12051113
TI  - Endometrial safety of a transdermal sequential estradiol-levonorgestrel
      combination.
AB  - OBJECTIVE: The aim of this 1-year, randomized, multinational, open-label study
      was to assess the effect on the endometrium of three dosages of estradiol and
      sequential levonorgestrel, each administered in a novel 7-day transdermal matrix
      patch. METHODS: A total of 468 postmenopausal women received patches of 15 cm2
      (50 micrograms/day estradiol for 2 weeks followed by 50 micrograms/day estradiol
      10 micrograms/day levonorgestrel for 2 weeks), 22.5 cm2 (75 micrograms/day
      estradiol for 2 weeks followed by 75 micrograms/day estradiol-15 micrograms/day
      levonorgestrel for 2 weeks) or 30 cm2 (100 micrograms/day estradiol for 2 weeks
      followed by 100 micrograms/day estradiol-20 micrograms/day levonorgestrel for 2
      weeks). Each patch was applied for 7 days. RESULTS: Endometrial biopsies were
      taken before and after 1 year of treatment, with final valid biopsy results being
      obtained in 399 women. There were two cases of endometrial hyperplasia (one in
      the 22.5-cm2 and one in the 30-cm2 group). All three doses of this 7-day
      sequential combined estradiol-levonorgestrel transdermal hormone replacement
      therapy therefore had excellent endometrial safety. The lowest dose, however, was
      associated with less bleeding and a somewhat different histological pattern,
      compared with the two higher doses. All three doses provided a high level of
      patient satisfaction with the bleeding response. CONCLUSION: Estradiol and
      sequential levonorgestrel administered in a 7-day transdermal matrix patch for 1
      year provide endometrial protection.

PMID- 12051115
TI  - Purified phytoestrogens in postmenopausal bone health: is there a role for
      genistein?
AB  - OBJECTIVE: Genistein is the main isoflavone present in soy and the one to which
      biological action is most often ascribed. There are suggestions that genistein
      could have a role as an osteoprotective agent. Hence, a review of the evidence
      has been undertaken. METHODS: MEDLINE (1966-August 2001), Allied Complementary
      Medicine (1985-2001), the Cochrane Library and the Database of Systematic Reviews
      (2nd Quarter 2001) were searched using the key words: genistein, osteoporosis,
      bone, isoflavones. RESULTS: Genistein appears to bind to the estrogen receptor
      (ER), with greatest affinity to ER beta. In vitro it stimulates protein synthesis
      in osteoblast cell lines, and in animal studies it appears to be effective in
      preventing bone loss caused by estrogen deficiency. There are no published human
      studies using pure genistein. CONCLUSION: Genistein appears to have a stimulatory
      effect on osteoblasts and, in some animal studies, it has been shown to exert an
      anabolic effect on bone. If these effects were to be demonstrated in humans,
      genistein would be a potentially useful oral anabolic agent for the treatment of
      osteoporosis.

PMID- 12051114
TI  - New animal model for the study of postmenopausal coronary and cerebral artery
      function: the Watanabe heritable hyperlipidemic rabbit fed on a diet avoiding
      phytoestrogens.
AB  - OBJECTIVE: To evaluate the effect of estrogen replacement therapy (ERT) on the
      functional characteristics of coronary and cerebral arteries in a new rabbit
      model for postmenopausal vascular function. METHODS: Female ovariectomized
      Watanabe heritable hyperlipidemic (WHHL) rabbits were randomized to treatment for
      16 weeks with either 17 beta-estradiol or placebo. The chow used was semi
      synthetic, thereby avoiding the influence of phytoestrogens. Ring segments of
      cerebral and coronary arteries were mounted for isometric tension recordings in
      myographs. The passive and active length-tension relationships for
      electromechanical (high potassium), pharmacomechanical (histamine) and combined
      electro- and pharmacomechanical (high potassium plus histamine) contraction were
      evaluated. RESULTS: Treatment with 17 beta-estradiol significantly changed the
      active length-tension relationship for the electromechanical response in the
      proximal coronary arteries. No changes were observed for the passive length
      tension relationships. CONCLUSIONS: Long-term treatment with 17 beta-estradiol
      lowered the electromechanical tonus of atherosclerotic coronary arteries
      proximally, where the atherosclerosis is most developed. This could be one of the
      mechanisms behind the putative protective effect of hormone replacement therapy
      against ischemic heart disease. The study presents a promising new animal model
      for the investigation of postmenopausal coronary and cerebral artery function.
      The data correspond well with epidemiological observations in postmenopausal
      women.

PMID- 12051116
TI  - Hormone replacement therapy and malignant melanoma: to prescribe or not to
      prescribe?
AB  - The mean age of presentation of malignant melanoma in women is the early fifties,
      a time that may be concomitant with the onset of the menopause. As the lesion can
      often be successfully surgically excised, many women will enter the menopause
      disease-free but in need of treatment for their menopausal symptoms. Melanoma has
      traditionally been considered to be an estrogen receptor-positive tumor, whose
      prognosis is adversely affected by estrogen, whether during pregnancy or in
      association with the oral contraceptive pill or hormone replacement therapy
      (HRT). Recent evidence now refutes this. As most recurrences occur in the first 2
      years following treatment, it may be prudent to defer HRT until this time. There
      is a particular paucity of information pertaining to HRT and melanoma, such that,
      at present, there appears to be no justification for withholding this potentially
      beneficial therapy from menopausal women who have undergone treatment for
      melanoma.

PMID- 12051117
TI  - Anthrax vaccine and causality assessment from individual case reports.

PMID- 12051118
TI  - Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee
      (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System
      (VAERS).
AB  - PURPOSE: To assess the safety of a licensed anthrax vaccine given to nearly
      400,000 US military personnel, reports of adverse events (AEs) submitted to the
      Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated
      medically. METHODS: The Anthrax Vaccine Expert Committee (AVEC), a civilian panel
      of private-sector physicians and other scientists, reviewed 602 VAERS reports
      using a Delphic approach (structured expert consensus) to assess the causal
      relationship between vaccination and the reported AEs and sought to identify
      unexpected patterns in the occurrence of medically important events. Reports were
      entered into a database and used to profile AEs with respect to person,
      type/location, relative frequency, severity/impact, concomitant illness or
      receipt of other drugs or vaccines, and vaccine lot. RESULTS: Nearly half the
      reports noted a local injection-site AE, with more than one-third of these
      involving a moderate to large degree of inflammation. Six events qualified as
      serious AEs (SAEs), and all were judged to be certain consequences of
      vaccination. Three-quarters of the reports cited a systemic AE (most common: flu
      like symptoms, malaise, rash, arthralgia, headache), but only six individual
      medically important events were judged possibly or probably due to vaccine
      (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2),
      bronchiolitis obliterans organizing pneumonia). CONCLUSIONS: Since some cases of
      local inflammation involved distal paresthesia, AVEC recommends giving
      subcutaneous injections of AVA over the inferior deltoid instead of the triceps
      to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation
      of VAERS reports does not suggest a high frequency or unusual pattern of serious
      or other medically important AEs.

PMID- 12051119
TI  - Contribution of pharmacists to the reporting of adverse drug reactions.
AB  - PURPOSE: The aim of the study is to get a better view about the possible
      contribution of pharmacists' reports to the quantity and the quality of reports
      and in this way to the quality of a voluntary reporting system of adverse drug
      reactions. METHODS: A total of 15,293 reports, sent to the Netherlands
      Pharmacovigilance Foundation Lareb between 1995 and 2000 were analysed for the
      characteristics of pharmacists' reports and the differences with reports from
      physicians i.e. dispersion of adverse drug reactions in relation to the different
      System and Organ Classes, the seriousness of the reports according to the CIOMS
      criteria and the documentation grade of the reports. A total of 200 reports were
      selected at random and their quality assessed. RESULTS: Pharmacists are
      responsible for 40% of the reports sent in to Lareb during this period. Their
      reports more frequently concern adverse effects in relation to skin and the eyes.
      Adverse drug reactions reported by pharmacists tend to be less severe than those
      reported by physicians and pharmacists' reports tend to be of a lower
      documentation grade than those of physicians. Also, the quality of the clinical
      information is higher in physicians' reports. CONCLUSIONS: The contribution of
      pharmacists to the voluntary reporting system in the Netherlands is of great
      importance, both for the number and quality of the reports.

PMID- 12051120
TI  - Validity and completeness of the General Practice Research Database for studies
      of inflammatory bowel disease.
AB  - PURPOSE: The objective of this study was to evaluate the validity and
      completeness of the General Practice Research Database (GPRD) as a tool for
      research into inflammatory bowel disease epidemiology. METHODS: Patients
      diagnosed with inflammatory bowel disease were identified from GPRD. Mailed
      surveys were sent to the general practitioner caring for a stratified random
      sample of 170 of these patients and collected information on the diagnosis of
      inflammatory bowel disease and the most recent surgery and hospitalization.
      RESULTS: Usable surveys were returned for 157 patients (92%). The inflammatory
      bowel disease diagnosis was highly probable or probable in 144 (92%, 95% CI 86 to
      96%). Among the 53 patients with a potentially incident inflammatory bowel
      disease diagnosis, 33 (62%) had the first recorded diagnosis in GPRD within 30
      days of the date reported in the survey (median difference -8 days; interquartile
      range 0 to -81 days). Of 12 surgeries and 25 hospitalizations reported in the
      survey, 11 (92%) and 19 (76%) were identified in GPRD, respectively. CONCLUSIONS:
      The diagnosis of inflammatory bowel disease in GPRD appears reliable for most
      patients. Important medical events such as hospitalizations and surgery are
      recorded at a high rate, although algorithms to identify these events are
      complex.

PMID- 12051121
TI  - Inpatient treatment of depression and associated hospital charges.
AB  - OBJECTIVE: We evaluated inpatient treatment of depression, prescribing patterns
      for antidepressants, and associated hospital charges. METHODS: We reviewed
      administrative data of the UCLA Neuropsychiatric Hospital between July 1994 and
      July 1997 for all 1698 hospitalizations for mood disorders. We evaluated drug
      utilization patterns and hospital charges by analysis of variance and multiple
      regression, and by stratifying on diagnosis, severity, age, and other factors.
      RESULTS: Length of stay was the major contributor to total charges, which
      included room charges and charges for services, procedures, supplies, and tests.
      The selective serotonin reuptake inhibitors (SSRIs) were prescribed most often
      (to 47% of patients), followed by the atypicals (heterocyclics, 12%), the
      tricyclics (TCAs, 7%), venlafaxine (7%) and the monoamine oxidase inhibitors
      (MAOIs, < 1%). The atypicals were given to the oldest patients. After controlling
      for length of stay, patient age, genders and comorbidity, the atypicals were
      associated with the highest total inpatient charges: $2000 more than MAOIs, $600
      more than SSRIs, and $600 more than venlafaxine. Higher charges were the result
      of more expensive procedures, especially ECT. DISCUSSION: The SSRIs were the most
      commonly used antidepressant. Charges for antidepressant medications contributed
      only 0.5% of total inpatient charges. Patients receiving atypicals had among the
      highest total charges, partly because of the higher use of ECT. They may
      represent a more severely depressed group who have not responded to other
      antidepressants.

PMID- 12051122
TI  - Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with
      the use of Vincristine: an over-representation of Asians?
AB  - PURPOSE: This retrospective study used a pharmaceutical company's global safety
      database to determine the reporting rate of hyponatremia and/or syndrome of
      inappropriate secretion of anti-diuretic hormone (SIADH) among vincristine
      treated patients and to explore the possibility of at-risk population subgroups.
      METHOD: We searched the Eli Lilly and Company's computerized adverse event
      database for all reported cases of hyponatremia and/or SIADH as of 1 November
      1999 that had been reported during the use of vincristine. RESULTS: A total of 76
      cases of hyponatremia and/or SIADH associated with vincristine use were
      identified. The overall reporting rate was estimated to be 1.3/100,000 treated
      patients. The average age of patients was 35.6 +/- 28.3 years, and 62% were
      males. Approximately 75% of the patients were receiving treatment for leukemia or
      lymphoma. Among the 39 reports that included information on race, the racial
      distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data
      suggest that Asian patients may be at increased risk of hyponatremia and/or SIADH
      associated with vincristine use. Although the overall reported rate of SIADH
      associated with vincristine is very low, physicians caring for Asian oncology
      patients should be aware of this potential serious but reversible adverse event.

PMID- 12051123
TI  - Adverse drug events in hospitalized patients treated with cardiovascular drugs
      and anticoagulants.
AB  - PURPOSE: To evaluate the incidence of serious adverse drug events (ADEs) caused
      by cardiovascular drugs during hospitalization in a department of internal
      medicine, and to identify patients at highest risk. PATIENTS AND METHODS: All the
      patients treated with cardiovascular drugs and/or anticoagulants in the
      department between November 1999 and January 2000 were recruited into the study.
      During hospitalization the patients' charts were reviewed by a pharmacist and a
      clinician, and the occurrence of serious ADEs was assessed using the Naranjo
      algorithm. 'Possible' and 'doubtful' ADEs were not counted. RESULTS: Of 496
      patients who were enrolled in the study, 20 (4%) had serious ADEs. Compared to
      patients without ADEs, patients in the ADE group were older (72 +/- 12.6 years
      (mean +/- SD) vs. 65 +/- 13 years, p = 0.048), their average stay in hospital was
      longer (7.3 +/- 5.5 days vs. 5.2 +/- 3.7 days, p = 0.018) and their mean urea
      levels were higher (10.8 +/- 9.3 mmol/l vs. 7.8 +/- 5.3 mmol/l, p = 0.027). The
      most frequent background pathologies of the 20 patients with ADEs were
      hypertension (in 18 (90%)) and atrial fibrillation (in nine (45%)). In 50% of the
      the ADE group there was a history of drug allergies. The ADEs recorded were
      bleeding in four (20%), arrhythmias in six (30%), orthostatic hypotension in six
      (30%) and skin necrosis, paranoid reaction, acute hepatitis and acute renal
      failure in four (20%). The causative drugs were warfarin (which accounted for 25%
      of the ADEs), beta-blockers (15%), propafenone (5%), amiodarone (5%), and Ca(2+)
      channel blockers, nitrates and diuretics (together accounting for 50% of ADEs).
      Drug combinations were implicated in 50% of ADE. CONCLUSIONS: Serious ADEs were
      developed by 4% of hospitalized patients taking cardiovascular drugs. Those at
      highest risk were older, were receiving multiple drug therapy and had higher urea
      levels. Warfarin and beta-blockers were the drugs causing the largest number of
      adverse effects. ADEs are an important cause of preventable morbidity, often with
      serious economic implications and special attention should be given to their
      prevention.

PMID- 12051125
TI  - The International Society of Pharmacovigilance.

PMID- 12051124
TI  - Utilization pattern of metamizole in northern Sweden and risk estimates of
      agranulocytosis.
AB  - OBJECTIVE: This study was carried out in order to investigate the utilization
      pattern of metamizole to better estimate the quantitative risk of agranulocytosis
      since a cluster of such cases have been observed in Sweden. METHODS: Cases of
      agranulocytosis submitted to the Swedish Adverse Drug Reactions Advisory
      Committee (SADRAC) between 1996 and 1999 were identified. Based on the
      utilization pattern of metamizole in inpatients at three hospitals and in
      outpatients in two counties in northern Sweden risk estimates of agranulocytosis
      during metamizole treatment were estimated. The utilization of metamizole was
      investigated by scanning 3567 case records at 10 hospital departments as well as
      stored prescriptions at six pharmacies during a 3-month study period. RESULTS:
      Ten cases of agranulocytosis during treatment with metamizole have been reported
      to SADRAC over the period 1996 to 1999. During the 3-month study period
      metamizole was prescribed to 666 (19%) inpatients. Of these, approximately 96%
      received the drug for less than 1 week, 7.2% had used the drug previously. At the
      participating pharmacies 112 metamizole prescriptions for outpatients were found.
      The drug was prescribed in 34% for less than 1 week, in 28% for 7-15 days, and in
      38% for more than 15 days. The mean prescribed daily dose was 2.7 g. Given
      certain assumptions including the actual amounts prescribed the calculated risks
      of agranulocytosis would be approximately one out of every 31,000 metamizole
      treated inpatients and one of every 1400 metamizole-treated outpatients.
      CONCLUSION: This study indicates that in most inpatients the use of metamizole in
      northern Sweden was within the approved indications for the drug. However, a
      considerable number of outpatients received the drug for a longer time than
      recommended and this may carry an increased risk for developing agranulocytosis.

PMID- 12051126
TI  - Pharmacoepidemiology and drug safety.

PMID- 12051127
TI  - Fracture strength of all-ceramic lithium disilicate and porcelain-fused-to-metal
      bridges for molar replacement after dynamic loading.
AB  - The replacement of missing posterior teeth using all-ceramic bridges remains a
      challenge. This study compares the fracture resistance of all-ceramic 3-unit
      bridges for the replacement of first molars to conventional porcelain-fused-to
      metal bridges. Human premolars and molars were used to create two test groups and
      one control group of 16 specimens each. To simulate clinical parameters, the
      specimens were exposed to cyclic fatigue loading in an artificial mouth with
      simultaneous thermocycling. All samples were thereafter exposed to fracture
      strength testing. Porcelain-fused-to-metal bridges showed significantly higher
      fracture strengths than all-ceramic bridges. However, the fracture strength of
      the all-ceramic bridges was higher than peak physiological chewing forces.

PMID- 12051128
TI  - Case report: removal of fractured endodontic posts with a sonic instrument.
AB  - Fracture of endodontic posts within the root canal system is one of the causes of
      failure to restore endodontically treated teeth. Various techniques, with varying
      degrees of success, have been proposed in the literature for the removal of
      fractured posts prior to re-restoring the tooth. This case report describes the
      use of a sonic device to dislodge and remove two fractured prefabricated metal
      endodontic posts from teeth UR1 and UL2. The reader is also introduced to a
      variety of post removal techniques available.

PMID- 12051129
TI  - Infiltration of resin into white spot caries-like lesions of enamel: an in vitro
      study.
AB  - The aim of this study was to determine the extent to which caries lesions can be
      infiltrated successfully with polymerisable resins. This could provide dentists
      with an additional means of managing white spot lesions in high caries risk
      patients rather than relying on improved plaque control and fluoride application.
      Artificial caries lesions were produced in extracted premolar teeth using an
      acidified gel. The lesions were infiltrated using two of the resins currently
      available to the dental profession. The effects of acid etching the surface, and
      of drying the lesion by two methods, were investigated. The degree of resin
      penetration was evaluated by scanning electron microscopy. The results showed
      that following a short etch (5s with 36% phosphoric acid), prior dehydration of
      the lesion with ethanol and the application of multiple layers of bonding resin,
      lesions could be infiltrated almost completely with organic resin. This approach
      could offer an alternative approach for the management of uncavitated lesions.

PMID- 12051130
TI  - Use of the Internet as a research method in a study of the emotional effects of
      tooth loss in Poland.
AB  - The study explored the use of the Internet to investigate the emotional effects
      of tooth loss in a Polish population. The Internet was used as a novel method of
      recruiting study participants. The study was announced on Internet pages in the
      Polish language inviting anyone who had lost some natural teeth to respond.
      Respondents were sent a questionnaire by e-mail, which they completed and
      returned by the same means. Twenty nine completed questionnaires were received in
      a twelve month period. The respondents were predominantly males under the age of
      50 years reflecting the profile of Internet users in Poland. Despite the sample
      bias, the results showed a trend similar to the findings of earlier studies into
      the emotional effects of tooth loss with many of the respondents reporting
      difficulty in coming to terms with the loss of some or all their natural teeth.

PMID- 12051131
TI  - An in vitro assessment of the erosive potential of some white wines.
AB  - The aim of this study was to assess the erosive potential of a number of white
      wines from different wine growing regions of the world. This was achieved by
      assessing the initial pH, the 'titratable acidity' content and the in vitro
      enamel loss after four hours using profilometry. Most of the white wines tested
      were at least as erosive as orange juice, while some wines, notably the cava,
      were significantly more erosive than orange juice.

PMID- 12051132
TI  - Dimensional change in dentures processed in silicone and stone moulds.
AB  - Anecdotal evidence suggests that many dental laboratories are surrounding the
      teeth and gingival margins of the wax patterns for complete dentures with
      silicone laboratory putty prior to investing in dental stone or plaster to
      facilitate deflasking and polishing. This project investigates differences in
      dimension during processing when putty is used. Two groups of ten standardised
      dentures, one group with silicone, one group without were processed. Cross arch
      measurements were made before and after processing using an eight hour curing
      cycle followed by slow cooling. No statistically significant difference in change
      in dimension was observed between the two groups, indicating that this is an
      acceptable method.

PMID- 12051133
TI  - Case report: restorative options in regional odontodysplasia.
AB  - A case of regional odontodysplasia in a 13 year old female is reported. The
      restorative options in this case are considered along with the rational for
      providing a dentine bonded all-porcelain bridge. This approach restored both
      function and aesthetics with minimum destruction to the hypoplastic tooth tissue
      of the abutment.

PMID- 12051134
TI  - The relationship between crown and post design on root stress--a finite element
      study.

PMID- 12051135
TI  - [Parelectric spectroscopy for noninvasive diagnosis of laryngeal tissue].
AB  - Under the influence of an external electrical field, every biological tissue
      displays characteristic parelectric properties that can be recorded by
      radiofrequency spectroscopy in a noninvasive contact mode. Parelectric
      spectroscopy was investigated for its utility as a complementary noninvasive
      diagnostic procedure in examinations of the larynx, in particular in terms of its
      ability to differentiate tissue properties. Parelectric spectroscopy was
      performed in 10 patients submitted to surgical ablation of vocal cord neoplasia
      under local or insufflation anaesthesia. Measurements were obtained in the area
      of the neoplasia, and in macroscopically normal tissue in the corresponding vocal
      cord. In all cases, intra-individual comparison with normal vocal cord tissue
      revealed lower dipole density and reduced mobility of the affected vocal cord. In
      addition, the difference between normal and pathological tissue in terms of the
      parelectric parameters increased with age. The absolute values of dipolar density
      and mobility revealed no tendency to correlate with different kinds of vocal cord
      neoplasia. Parelectric spectroscopy may be a useful additional diagnostic tool
      for monitoring the course of epithelial changes in the larynx.

PMID- 12051136
TI  - [Changes in cerebral near infrared spectroscopy parameters during manual
      acupuncture needle stimulation].
AB  - Near-infrared spectroscopy (NIRO 300, Hamamatsu Photonics, Japan) was used to
      monitor human cerebral function in the central region during manual acupuncture
      needle stimulation of the large intestine 4 (LI.4) point in 16 adult volunteers
      (9 females, 7 males; mean age 23.9 +/- 6.0 (SD) years, range 19-45 years). We
      found a significant (p < 0.001) decrease in oxyhaemoglobin after needle insertion
      and stimulation (duration 20 sec.), accompanied by an increase (p = 0.003) in
      deoxyhaemoglobin. A repeat stimulation showed similar effects. Cytochrome oxidase
      aa3 remained unchanged during stimulation. The results demonstrate that near
      infrared spectroscopy may be a noninvasive method of measuring regional changes
      in cerebral haemodynamics resulting from peripheral acupuncture stimulation.

PMID- 12051137
TI  - [Development of a nonmagnetic angle encoder for active shielding during
      biomagnetic measurements].
AB  - Biomagnetic fields--in particular in the low-frequency range--are subject to
      environmental interference, which cannot be adequately reduced by most passive
      shielding methods. However, the signal-to-noise ratio can be increased by active
      compensation. For this purpose, the interference is detected by reference sensors
      and fed back through integrated compensation coils. To establish deviation of
      normal directions between reference sensors and compensation coils, an angle
      encoder was developed. The rotation of the reference sensors about two axes at
      right angles to each other, is converted into voltage pulses by means of
      codewheels and photoelectric beams. The pulses are counted by incremental
      encoders, and represent a measure of the angles. A cardanic suspension and a
      plumb-line act as a reference system. The pulses counted are converted into
      binary angle values, which are used for coordinate transformation of the
      interfering fields. The angle encoder can determine the tilt of the reference
      sensors with an accuracy of 1 degree within a range between -45 and +45 degrees.
      The noise level of the system remains unaffected during a biomagnetic
      measurement. Magnetic signals of up to 5 pT arising during the oscillation of the
      plumb-line can be neglected because of the static nature of the angular
      measurement.

PMID- 12051138
TI  - [Computer-assisted development of epitheses after optical recording of facial
      defects].
AB  - A major drawback of conventional impression techniques used for customizing
      facial prostheses is the fact that pressure applied deforms soft tissue, thus
      reducing accuracy and causing patient discomfort. A possible solution is the use
      of optical 3-D coordinate measuring techniques, such as the fringe projection
      technique, which enables precise and contact-free recording of facial surfaces.
      The application of this method is demonstrated on a patient who lost his left eye
      and part of the jaw bone during surgery for cancer. 3-D CAD software that
      supports the construction of a facial prosthesis from the data obtained has been
      developed. For this purpose, spline functions are used to define border curves,
      and the intact half of the face is used as a model for the prosthetic surface.
      The resulting digital data are used to construct first a model made of synthetic
      resin, and then a final wax model with the aid of rapid prototyping techniques.

PMID- 12051139
TI  - [Spinal load bearing during sitting in an office chair with a tilting back].
AB  - Long periods of quiet sitting is considered a cause of low back pain. It is often
      assumed that spinal loads are high, especially when sitting erect. Modern office
      chairs with a tiltable back permit changes in the seated posture. In the most
      reclined position, some new chairs even match a kyphotic form of the lumbar
      spine. It is assumed that sitting on such a chair reduces low back pain. With the
      aim of determining spinal loading in different sitting positions, the loads
      acting on implanted fixation devices were measured telemetrically in two
      patients. Loads were measured in patients sitting on six different chairs with
      tiltable backs. In modern chairs, implant loading was always lower than while
      walking. In the end-tilt position of the chairback, loads were always lower than
      when the chairback was upright. Even when the lordotic curvature of the lumbar
      spine was "corrected", loads on the fixator were lower than when the subject was
      seated in the upright position. In a modern chair, spinal loading is no higher
      than with non-adjustable office chairs.

PMID- 12051140
TI  - [Is there a correlation between clinical results or quality of life and
      radiological findings after implantation of a total knee prosthesis?].
AB  - AIM OF THE STUDY: To establish whether there is a clinical correlation between
      clinical outcome or quality of life and radiographic findings. MATERIAL AND
      METHODS: 17 patients (mean age 68.2 years) with total knee arthroplasty were
      examined after an average follow-up of 24.6 months. The examination included the
      HSS score for clinical parameters, and the SF-36 questionnaire quality of life.
      Radiographs were evaluated in accordance with Ewald and Lotke, and a schema of
      our own. RESULTS: The HSS score returned a mean of 81 points, and the SF-36
      questionnaire showed significantly poorer results in comparison with age-matched
      healthy subjects. The Lotke evaluation of the X-rays showed a mean value of 76.3.
      Correlations between the radiographic findings and the HSS score were not seen.
      Correlations between X-ray parameters (Ewald and Lotke) and the SF-36 were found
      only for pain and vitality. CONCLUSIONS: This is the first study to investigate
      the correlation between clinical parameters (including quality of life) and X-ray
      findings. Neither the clinical score nor the quality of life score was found to
      correlate with the radiographic findings. Nor was more than minimal correlation
      found between quality of life and HSS score. These results show that the presence
      of radiolucent lines or deviations from the perfect prosthesis position must not
      necessarily be considered to be of importance for clinical outcome and quality of
      life.

PMID- 12051141
TI  - Infectious diseases of refugees and immigrants: hookworm.

PMID- 12051142
TI  - Identification, evaluation, and treatment of overweight and obese adults.
AB  - This month's CPG review is on overweight and obese adults. With an estimated 97
      million or more adults in the United States who are overweight or obese and as
      the second leading cause of preventable death in the United States, this
      guideline is expected to be of wide interest to nurse practitioners.

PMID- 12051143
TI  - Early recognition of Marfan's syndrome.
AB  - PURPOSE: To describe the classical features of Marfan's syndrome to help nurse
      practitioners (NPs) diagnose it in the early stages of progression and perhaps
      prevent many of its deleterious effects. DATA SOURCES: Selected research-based
      articles in the scientific literature and classic medical texts. CONCLUSIONS: The
      cause of Marfan's syndrome is unknown, but studies have linked it with a disorder
      of chromosome 15. It is a degenerative connective tissue disorder that affects
      the musculoskeletal, ocular, integumentary, respiratory, and neurologic systems.
      The most lethal effect is on the cardiovascular system causing dissecting aortic
      aneurysms. IMPLICATIONS FOR PRACTICE: Early diagnosis is essential for a positive
      course of management. Marfan's syndrome can have fatal consequences and is often
      underdiagnosed and misdiagnosed.

PMID- 12051144
TI  - Gaining insight into age-related macular degeneration.
AB  - PURPOSE/OBJECTIVE: To enhance nurse practitioner (NP) recognition of clients with
      age-related macular degeneration (AMD) based on history and physical examination
      findings, to encourage prompt initial referral of these clients to an
      ophthalmologist for a treatment evaluation, and to acquaint NPs with low vision
      rehabilitation services. DATA SOURCES: Government documents, professional
      association practice guidelines, original research articles, journal articles,
      and Internet resources. CONCLUSIONS: Age-related macular degeneration is a
      common, chronic vision-threatening condition necessitating prompt recognition and
      professional evaluation. If not recognized early, AMD can lead to low vision and
      a diminished quality of life for the elderly client. IMPLICATIONS FOR PRACTICE:
      Even though NPs have a limited role in the treatment of AMD, they are in an
      instrumental position as a primary care providers to screen for this disease
      chiefly by: (a) adherence to eye examinations intervals, (b) recognition of risk
      factors, (c) use of the Amsler grid, (d) awareness of psychosocial dimensions,
      (e) making appropriate referrals, and (f) advocating low vision rehabilitation
      services.

PMID- 12051145
TI  - Trends in mental health: implications for advanced practice nurses.
AB  - PURPOSE: To examine current trends in mental health care for vulnerable
      populations and suggest how advanced practice nurses (APNs) can incorporate
      mental health care into primary care practice. DATA SOURCES: Original research
      and evidence-based clinical articles, government publications, and professional
      practice guidelines. CONCLUSIONS: Vulnerable populations, such as racial and
      ethnic minorities, adults with chronic mental illness, the elderly, the
      incarcerated, and those living in rural areas have long been ignored as
      recipients of quality, integrated health care services. There is a compelling
      need for APNs to participate in the integrated delivery of physical and mental
      health care to all Americans, especially to vulnerable populations. IMPLICATIONS
      FOR PRACTICE: Under the umbrella of advanced practice nursing, a variety of nurse
      practitioners (NPs) and clinical nurse specialists (CNSs) can offer a holistic
      approach to the provision of evidence-based health care in a wide variety of
      settings to an array of vulnerable and underserved people. By serving on provider
      panels, partnering with consumer groups, and advocating for the unmet health
      needs of vulnerable populations, APNs can have a positive impact on the health
      care delivery system.

PMID- 12051146
TI  - Outcomes of a community-based three-year breast and cervical cancer screening
      program for medically underserved, low income women.
AB  - PURPOSE: To evaluate a community level three-year breast and cervical cancer
      screening program for medically underserved, low income women. DATA SOURCES:
      Descriptive data on 128 women gathered from five semiannual screening programs
      held between 1995 and 1997 were analyzed. CONCLUSIONS: Poor and medically under
      served women often face barriers that may discourage or prevent screening
      activity and measures for early detection of breast and cervical cancer. Besides
      success in recruiting women to the program, community collaborative partnerships
      were established that continue to sustain this program. IMPLICATIONS FOR
      PRACTICE: The results from this project provide an example of how advance
      practice nurses (APNs) can demonstrate meaningful and competitive health care
      services for underserved women and how APNs can actively evaluate programs they
      offer that affect the health practices of communities in need.

PMID- 12051147
TI  - Increasing awareness of asthma and asthma resources in communities on the
      southwest border.
AB  - PURPOSE: To provide outpatient asthma education for children and families along
      the southwest border of the U.S. and to study the effectiveness of a southwest
      border hospital's in-house asthma educational program. DATA SOURCES: (1)
      "Increasing the Knowledge Base of Asthmatics and Their Families through Asthma
      Clubs along the Southwest Border." (2) American Lung Association. (3) National
      Institutes of Health, National Heart, Lung and Blood Institute. (4) Referrals
      from a southwest border hospital. CONCLUSIONS: Only two of 23 patients referred
      for asthma follow-up were readmitted to hospital and/or emergency care during the
      following year. Large group teaching pretest-posttest score means for 3,429
      fourth and fifth grade students revealed a 23% increase in asthma knowledge.
      Small follow-up groups of students received in-depth asthma education.
      IMPLICATIONS FOR PRACTICE: Effectiveness of hospital inpatient asthma education
      combined with outpatient family follow-up was supported. An additional finding
      was that southwest border families are more receptive to visits arranged with a
      school nurse in their children's school than to home visits from primary care
      clinic nurses.

PMID- 12051148
TI  - [Progress in physiology and ergonomics and its significance for occupational
      hygiene].
AB  - Over the recent decades, advancements in occupational physiology and occupational
      psychology have primarily been observed in two domains: the increased knowledge
      of mechanisms responsible for the development of physical and mental fatigue and
      the elaboration of new methods facilitating their quantitative assessment. The
      way these advancements have been utilized and the range of their application
      result from new hygiene requirements imposed by the changed context and
      organization of work. The integration of these scientific disciplines is best
      accomplished in ergonomics, particularly through designing and optimization of
      working conditions in view of the best possible adjustment of technology and work
      organization to the psycho-physical needs of workers. Changes in occupational
      activities are associated with a gradual replacement of jobs that require much
      dynamic effort by those that involve static and mental efforts. Classic
      occupational physiology dealing with systemic changes occurring during a dynamic
      effort is largely superseded by studies (biochemical and electrophysiological) of
      changes in cellular physiology evoked by static effort and changes that accompany
      mental overload and stress. Over the last few years, occupational physiology and
      ergonomics have faced a number of macroproblems of demographic nature, e.g. aging
      of the population, and a growing number of people with disabilities who have to
      be employed. It is now the responsibility of ergonomics to create working
      conditions taking account of the needs of these particular occupational groups. A
      significant methodological progress has been made due to new opportunities, which
      allow to simulate and model situations with body overload. New methods are based
      on computerized programs that incorporate data from all fields necessary to
      assess and design working conditions (anthropometry, biomechanics, safety
      engineering etc.).

PMID- 12051149
TI  - [Occupational diseases--epidemiologic evaluation of the situation in Poland].
AB  - The incidence of occupational diseases is one of the basic indices of the
      effectiveness of prevention in the area of occupational health. It allows for the
      identification of jobs, plants and branches of the national economy with
      potentially increased risks for pathologies induced by working conditions.
      However, we should be aware of the fact that many of the recently diagnosed
      diseases result from long-term exposures experienced at work sites which are no
      longer under operation. The analysis was based on data included in occupational
      disease certificates. All sanitary and epidemiological stations throughout the
      country are committed to notify cases of occupational diseases to the National
      Register of Occupational Diseases at the Nofer Institute of Occupational Medicine
      in Lodz. After a significant increase in the number of occupational diseases
      (8305-12,017 cases per year) observed in 1980-1998, its decrease has been noted
      in Poland over the recent two years (9982 cases in 1999 and 7339 in 2000). In
      1998-2000, a substantial decrease in the decreasing rate was also found (from
      117.3 to 73.9 per 100,000 employed), which means that the decreasing trend does
      not result only from the increasing size of the working population in Poland. In
      2000 like in previous years, among occupational diseases the following ones were
      most often diagnosed: diseases of vocal organ due to excessive voice effort most
      common in teachers, occupational hearing loss, pneumoconiosis, contagious and
      invasive diseases, dermatoses, chronic diseases of bronchi, vibration syndrome as
      well as acute and chronic poisonings. There were registered 6626 cases of the
      above listed diseases, that is 90.3% of all occupational diseases. In 1998-2000,
      a significant decrease in the incidence of this category of diseases was noted.
      The largest decrease applied to the vocal organ diseases, occupational hearing
      loss and contagious and invasive diseases (by 30%, 51% and 40%, respectively).
      Neither in the member states of the European Union, nor in the USA, vocal organ
      pathologies are listed among occupational diseases. The main reason for this is
      an inappropriate medical prevention in the group of teachers and somewhat limited
      opportunity to teach them how to use techniques of voice emission. A decreased
      incidence of occupational diseases observed in Poland in 1998-2000 results partly
      from improvements in working conditions and partly from more effective
      prevention.

PMID- 12051150
TI  - [Biologic factors hazardous to health: classification and criteria of exposure
      assessment].
AB  - Occupational biohazards include not only factors that have long been known
      (viruses, bacteria, fungi, parasites), but also agents exerting allergic and
      toxic effects, which are directly responsible for the development of various
      diseases in many occupational groups. Numerous agents of this group (allergens,
      microbial toxins, pollen allergens and allergens of animal origin) are components
      of bioacrosols--potential hazards inducing occupational respiratory diseases
      among farmers and people involved in other occupations. Contrary to the majority
      of chemical and physical factors, neither commonly approved criteria for
      assessing exposure to biological factors, nor threshold values and methodological
      recommendations are as yet available. The lack of these criteria renders it
      difficult to implement in Poland and in other countries Directive 2000/54/EC on
      the protection of workers against the risk of occupational exposure to
      biohazards, issued by the European Community. The Institute of Rural Medicine in
      Lublin has drafted the proposals for threshold limit values of occupational
      exposure to bioaerosols associated with plant and animal dusts, including:
      mesophilic bacteria, Gram-negative bacteria, thermophilic actinomycetes, fungi
      and bacterial endotoxins. These proposals could be considered as a starting point
      for developing appropriate facultative standards that would facilitate the
      practical implementation of the aforesaid Directive. Meantime it is essential to
      be strict in following the binding concentration limits of the plant and animal
      dusts in the air.

PMID- 12051151
TI  - [Quality assurance tests in industrial hygiene laboratories].
AB  - In order to achieve and maintain an accreditation, the requirements laid down in
      a new standard (ISO/IEC 17025) should be met by laboratories. This paper presents
      the interpretation and some comments on the aforesaid requirements in the
      specific area of activities carried out by industrial hygiene laboratories. In
      particular, the author refers to the management requirements (organization,
      quality system, document control, service to the client, corrective and
      preventive actions) and technical competence (personnel, facilities, equipment,
      tests and sampling methods, quality control, reporting etc.).

PMID- 12051152
TI  - [Economic transformations and their significance for occupational medicine and
      hygiene].
AB  - Poland's accession to the European Union entails the need to formulate our
      strategic goals also in occupational medicine. The most important trends, as well
      as the changes in world economy are presented with special reference to their
      impact on occupational medicine. The changing goals of occupational medicine and
      occupational hygiene in the Polish economy during the period of transition are
      discussed. The research priorities and the EU policy in these areas are
      highlighed. The intention of this paper is to initiate a general discussion in
      "Medycyna Pracy" on the future of occupational health service and occupational
      hygiene in Poland.

PMID- 12051153
TI  - [Criteria for evaluating exposure to chemical substances in Poland: procedures
      for suppression and applications].
AB  - The major objective of setting values of chemical concentrations in the work
      environment is to reduce the risk of occupation-related exposure to levels
      regarded as safe to humans. In the standard setting process, a critical
      assessment of the available literature data on toxicity of a given chemical and
      related health effects in the population exposed, depending on concentrations and
      exposure duration, is essential. Such an assessment performed by a group of
      experts is a difficult and responsible task since the available data are
      frequently incomplete and extrapolation of the results of animal experiments
      aimed at setting limits of concentrations safe to humans raises multiple doubts.
      The aim of this paper was to compare the procedures of setting permissible values
      for chemical factors in Poland and throughout the world and to highlight
      differences in their interpretation. In addition, a brief history of setting
      admissible limits, as well as definitions of hygiene standards used in Poland,
      the USA, Germany, the UK and in the former Soviet Union together with the ways of
      their formulation are presented. The country-to-country variations of attitudes
      towards setting admissible levels of exposure to carcinogenic agents are worthy
      of special mention. Maximum admissible concentrations of chemicals in the work
      environment suggested by experts and adopted by the state administration should
      not be regarded as constant and completely safe to the human health, thus the
      existing systems should take account of the need to verify these values with an
      inflow of updated information on chemical toxicity.

PMID- 12051154
TI  - [The state of working conditions in light of control recommendations issued by
      the State Labor Inspectorate--selected problems].
AB  - In enterprises covered by the scheme of the intensified supervision of the State
      Labor Inspectorate (SLI), working conditions are analyzed every year, and the
      measures to reduce or eliminate existing hazards are evaluated. The enterprises
      with high rates of accidents at work and employees exposed to hazardous chemical
      and physical factors present in the work environment are classified in this
      category. The list of such enterprises is subjected to annual verification.
      Enterprises with potential high or increased risk for serious industrial
      accidents involving noxious chemicals or dangerous for the local environment are
      also taken into account. The supervision of the State Labor Inspectorate, lasting
      already for a number of years, greatly contributed--this is confirmed by numerous
      inspections--to the sustained improvement of working conditions in enterprises of
      this category. In accord with the suggestions made by parliamentarians, the issue
      of intensified supervision of enterprises, representing various branches of the
      national economy, characterized by the highest rates of occupational hazards has
      been incorporated into the SLI Plan of Action for the years 2001-2003. In January
      2001, district inspectorates selected 137 enterprises of various sectors with the
      highest hazard rates to be covered by the SLI scheme in the nearest future. The
      systematic control and promotion activities will be aimed at eliminating or
      substantial reduction of reported hazards. In the previous year, the SLI tried to
      find out how far the employers fulfill their obligation to check technical
      conditions in their enterprises, as well as to discuss the possibility of further
      use of asbestos-containing products. In the opinion of the SLI, the employers do
      not comply with these requirements, or they are not willing to bear costs of
      removal or repair of asbestos-containing products. They postpone endlessly all
      necessary repairs. It is still impossible to evaluate the situation and to
      explicitly state that after completing works involving asbestos it is removed
      from premises designed for people. This is of paramount importance for safety of
      people at schools, kindergartens, high schools, as well as of hospital personnel
      and patients. In Polish regulations, the maximum admissible concentrations of
      asbestos for this kind of premises have no as yet been set. The State Labor
      Inspector has submitted a motion to the Minister of Health on setting permissible
      concentrations of asbestos dust in premises meant for people. The regulation
      (still binding) of March 12, 1996 on admissible concentrations and intensities of
      factors harmful to the human health, emitted by construction materials, devices
      and equipment in premises intended for people does not take account of asbestos.

PMID- 12051155
TI  - [Work conditions as evaluated by workers].
AB  - In the Polish professional literature we can more and more often find articles on
      working conditions and occupational risk. However, there is lack of information
      concerning the employees' knowledge of working conditions and possible
      occupational hazards. According to the Article 226 of the Labour Code the
      aemployer is obliged to inform employees on working conditions and relevant
      health hazards as well as hazards protection principles. Thus all the employees
      should know working conditions and relevant health hazards. The aim of the
      article is to prove the knowledge of working conditions and health hazards by the
      employees doing different jobs in several sectors of the national economy. There
      have been analyzed questionnaires received from 787 employees including 526 women
      and 261 men representing white-collar and blue-collar professions in industry
      sectors and services. Questionnaires have been collaborated by the Institute of
      Labour and Social Policy.

PMID- 12051156
TI  - [Health effects of occupational exposure to chemical substances in smokers'
      tobacco].
AB  - Based on the literature, devoted primarily to epidemiological studies, major
      health effects of combined exposure to chemicals and tobacco smoke are discussed.
      Among various effects, the following are taken into consideration: neoplasms with
      special concern for lung cancer, respiratory and cardiovascular diseases.
      Relative risks of these diseases and the absolute risk of lung cancer associated
      with exposure to polycyclic aromatic hydrocarbons are presented. In conclusion,
      smoking history should be taken into account during prophylactic examinations of
      workers.

PMID- 12051157
TI  - [Characteristics of sleep and locomotor activity in night shift workers].
AB  - Shift work and night work in particular, account for numerous disturbances in
      circadian biological rhythms of physiological activities. Shift workers most
      frequently complain of sleep disturbances manifested among others by sleep
      duration and quality, as well as by time of proper sleep and naps. Among methods
      used for the sleep assessment, subjective tests: sleep value questionnaires and
      24-h EEG, are most common, however actigraphy is recently considered to be more
      useful. This paper presents the results of the authors' investigations on the
      circadian rhythms: locomotor activity and sleep in air traffic controllers (ATCs)
      at the Okecie Airport of Warsaw. Sleep disturbances, most often sleep latency,
      shortening of the main sleep and more frequent naps increase with age and work
      experience. The knowledge of sleep disturbances may, in individual cases, be
      helpful in choosing the best possible strategy to cope with sleep deficit in
      shift workers.

PMID- 12051158
TI  - [Intramural hearing protection program as a response to health needs of working
      populations in the region of Swietokrysk].
AB  - The program of health promotion in the area of hearing protection (IHPP) is
      proposed as a part of Operational Target 8 of the National Health Program
      "Reducing exposure to harmful factors in the living, working and educational
      environment and mitigating their health effects" and corresponds with the aims of
      the Strategic Governmental Program on Health Protection and Safety at Work. Both
      in Poland and in the region of swietokrzyskie there is an urgent need to
      undertake appropriate steps to protect the hearing organ in the working
      population against harmful effects present in the work environment. It is
      estimated that 25% of diagnosed occupational diseases is associated with
      occupational hearing loss. The program is addressed to workers exposed to noise
      at work. To achieve the main goal of the program it is necessary: to reduce noise
      emissions and exposure to noise in the work environment; to promote behavior
      conducive to hearing protection among workers exposed to noise; to improve the
      quality of prevention in the occupational health services responsible for hearing
      protection. The Regional Center of Occupational Medicine in Kielce (coordinator)
      and primary units of occupational health service are involved in the
      implementation of the program, whereas, employers, occupational safety and health
      services, the State Labor Inspectorate and Sanitary Inspectorate participate in
      its implementation. It is expected that the program in the region of
      swietokrzyskie will yield the following expected results: the reduction of noise
      emission to safe levels; the increased awareness of using optimal hearing
      protectors among noise-exposed workers; the decreased number of workers with
      diagnosed noise-induced hearing loss, and the decrease in the number of new cases
      of occupational hearing impairment.

PMID- 12051159
TI  - [Reduction of dust during manual grinding of cast iron].
AB  - The method for determining the emission of dust and the effectiveness of dust
      removal from machines and devices by local exhaust ventilation to the workplace
      air is presented. This method consists in determining concentrations of air
      pollution in the measuring duct through which it is sucked off from the chambers
      with tested devices. At the same time the volume of air flow rate is measured. A
      laser dust analyzer is used to measure dust concentrations in the air. Air is
      sampled with isokinetic sampling heads. It was shown that dust emission at
      different kinds of manual grinding of cast iron without ventilation was between
      24 mg/min and 8131 mg/min, whereas with the use of local exhaust ventilation it
      decreased below 35 mg/min. The efficiency of the exhaust elements was over 95% at
      optimum use of local ventilation.

PMID- 12051160
TI  - [Undergraduate and postgraduate training in occupational hygiene (and medicine)
      during non-medical studies].
AB  - It is well known that the employer bears the responsibility for all what is going
      on in every type of enterprise. Polish high schools (all types) do not provide
      future managers with full range of education as they do not teach their alumni
      about occupational medicine and hygiene. Curricula should include classes devoted
      to the presentation and discussion of the Labor Code, work safety management,
      preplacement examinations, occupational diseases, work-related diseases,
      accidents at work and their effects. The aim of this study is to make clear to
      our field specialists that there is an urgent need to create an adequate lobby
      promoting occupational hygiene and medicine in order to raise their position and
      to facilitate contacts with employers.

PMID- 12051161
TI  - Medical privacy and its value for patients.
AB  - OBJECTIVES: To review privacy issues of medical information and current legal
      guidelines. DATA SOURCES: Government regulations and reports. CONCLUSIONS:
      Patients must have trust and confidence that the health care system will
      safeguard their health information and that it will not be used to discriminate
      against them through insurance or employment. IMPLICATIONS FOR NURSING PRACTICE:
      Health care professionals must be sensitive to the privacy needs of patients
      during the collection and storage of data, the access to information, and the
      sharing of patient information.

PMID- 12051163
TI  - Effective nursing documentation and communication.
AB  - OBJECTIVES: To identify the documentation and communication requirements an
      oncology nurse should follow to avoid negligence or malpractice suits. DATA
      SOURCES: Lexis, Medline, Westlaw, nursing and medical literature, and nursing
      legtal texts. CONCLUSIONS: Effective communication and documentation is an
      essential part of an oncology nurses' role and will reduce the risk of liability.
      IMPLICATIONS FOR NURSING PRACTICE: The old adage "not documented, not done"
      applies more today than ever before. Continuous, meticulous documentation and
      communication are essential for quality care as well as reduction of liability in
      every setting the oncology nurse practices.

PMID- 12051162
TI  - Medication misadventure in cancer care.
AB  - OBJECTIVES: To describe the nature and scope of the problem of medication errors
      in health care, with specific implications for error reduction and prevention.
      DATA SOURCES: Articles and research studies. CONCLUSIONS: Because of the
      complexity of chemotherapeutic regimens, requirements for supportive care drugs,
      and the physiologic vulnerability of patients due to their malignancies and
      intensive therapies, patients with cancer should be the focus of
      interdisciplinary medication error prevention programs. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses play a critical role in patient safety and the implementation of
      preventive and risk-reducing interventions to improve the drug delivery process.

PMID- 12051164
TI  - Legal issues in the early detection and monitoring of cancer.
AB  - OBJECTIVES: To identify the legal and ethical issues involved in the
      detection/monitoring of cancer. DATA SOURCES: Westlaw, Lexis, Medline, and legal
      and nursing literature. CONCLUSIONS: The introduction of genetic predisposition
      to cancer has increased the legal and ethical issues associated with the
      detection of cancer. IMPLICATIONS FOR NURSING PRACTICE: The expanding role of
      nurses has opened up many exciting new roles in the area of early detection of
      cancer including genetic counseling. Along with the new opportunities comes
      increased legal liability and ethical controversies that oncology nurses must be
      aware of.

PMID- 12051165
TI  - Ethical issues in pain management.
AB  - OBJECTIVE: To review the ethical principles of autonomy, nonmaleficence,
      beneficence, and justice to assist in understanding nursing's ethical obligation
      to patients and families in the practice of pain management. DATA SOURCES:
      Position papers, government guidelines, and nursing and legal literature.
      CONCLUSION: Cancer pain management has been an issue in nursing and medical
      practice for more than a quarter of a century. Today we have numerous
      organisations that focus exclusively on the issue of pain and yet the oncology
      patient continues to have inadequate pain control. IMPLICATIONS FOR NURSING
      PRACTICE: With the acknowledgement that we have the technical skills and the
      physiological knowledge to reduce pain, yet it is not being done, health care
      professionals have begun to explore the ethics behind pain.

PMID- 12051166
TI  - End-of-life care: legal and ethical considerations.
AB  - OBJECTIVE: To prepare the oncology nurse, under the Patient Self-Determination
      Act, to analyze and discuss legal and ethical issues that may arise in the
      clinical area when end-of-life decisions are made. DATA SOURCES: Nursing
      textbooks, scholarly articles, court cases, and internet publications.
      CONCLUSIONS: The dying patient has the right to die with dignity, respect, and
      the right treatment choices. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to
      understand how to implement the Patient Self-Determination Act regarding living
      wills, do not resuscitate orders, euthanasia, and whether or not to use feeding
      tubes.

PMID- 12051167
TI  - Impact of managed care on oncology.
AB  - OBJECTIVE: To review the general principles of managed care, including purpose,
      concept of risk, insurance mechanisms, and types of reimbursement. DATA SOURCES:
      Textbooks and journal articles. CONCLUSIONS: At times, managed health care may
      restrict the options available to the consumer and the provider of care and can
      lead to ethical and legal issues. IMPLICATIONS FOR NURSING PRACTICE:
      Practitioners caring for cancer patients must continue to monitor and participate
      in outcomes research to clarify the impact of managed care on cancer treatment.

PMID- 12051168
TI  - The oncology nurse: responsibilities under oath.
AB  - OBJECTIVES: To examine the role and responsibilities of the nurse as a fact
      witness and an expert witness in legal proceedings, and provide practical
      instruction regarding testifying in either capacity. DATA SOURCES: Federal rules,
      legal literature, and nursing articles. CONCLUSIONS: The nursing professional can
      serve the health care profession and the justice system by participating in the
      legal process. IMPLICATIONS FOR NURSING PRACTICE: By participating in the legal
      process, nurses define and uphold the appropriate standard of care, and in so
      doing, preserve quality health care.

PMID- 12051169
TI  - Legal and ethical issues confronting oncology nursing.
AB  - OBJECTIVES: To identify and summarize the legal and ethical issues found in the
      multiple settings in which oncology nurses practice. DATA SOURCES: Lexis,
      Medline, Westlaw, federal and state laws, government documents, and nursing and
      medical textbooks. CONCLUSIONS: Oncology nurses face many legal and ethical
      dilemmas when delivering care. The best defense against litigation is to be
      knowledgeable about the specific issues found in each setting, the impact these
      issues have on practice, and requisite risk reduction practices. IMPLICATIONS FOR
      NURSING PRACTICE: With the advent of new technology, changing state and federal
      laws, and new court decisions, the ethical and legal issues nurses will encounter
      when taking care of cancer patients will not remain the same. Continuing
      education will be essential if nurses are to remain current, lower their legal
      liability, and deliver quality care.

PMID- 12051171
TI  - Proceedings of the Third European Congress on Nutrition and Health in Elderly
      People. Madrid, Spain. November 23-25, 2000.

PMID- 12051170
TI  - Introduction to the law.
AB  - OBJECTIVES: To provide an introduction to the legal concepts that are involved in
      negligence suits involving oncology nurses. DATA SOURCES: Medline, Lexis,
      Westlaw, legal literature and texts. CONCLUSIONS: To avoid liability and guard
      against negligence or malpractice suits, the oncology nurse must be aware of the
      legal responsibilities of each aspect of the nursing role. IMPLICATIONS FOR
      NURSING PRACTICE: Protecting yourself against medical malpractice begins by
      understanding terms and concepts that are essential in instituting legal action
      against the nurse and incorporating the appropriate risk reduction practices into
      daily practice.

PMID- 12051172
TI  - Obituary: Associate Professor Maria Jolanta Mokrosz, Ph.D. (1949-2001).

PMID- 12051173
TI  - [Patient care and ethics. IV. The terminal patient who concealed the truth].
AB  - In this article a case is discussed in which a dentist is placed in a dilemma. He
      is working on a comprehensive treatment but his patient has deliberately
      concealed his terminal state of health. By chance he was told about the actual
      health situation of his patient. The question is discussed whether there is a
      moral justification to carry on with the treatment.

PMID- 12051174
TI  - [Identification of bacteria using DNA probes].
AB  - Since the microbial specificity of periodontal diseases is well established,
      having a valid microbial diagnostic test is essential for a correct and a
      coherent treatment planning. DNA probe will be used to identify and quantify the
      oral pathogens, most commonly associated with periodontitis. This test utilizes
      innovative DNA probe technology to identify unique segments of DNA in each of the
      following bacteria: Bacteroides gingivalis, Bacteroides intermedius,
      Actinobacillus actinomycetemcomitans, Wollinella recta, Fusobacterium nucleatum
      and the spirochete, Treponema denticola.

PMID- 12051175
TI  - [The stability of orthodontic treatment over the long term].
AB  - The long term stability of orthodontic treatment was evaluated in 7 orthodontic
      patients who were three to 12 years out of retention. Dental relationships and
      irregularities in the dental arch were recorded and scored on study models taken
      prior to orthodontic treatment, at the end of active treatment, and at long term
      follow up. Lateral skull radiographs taken at the start of active treatment were
      also analysed. According to the (mal)occlusion observed on the post-retention
      study models it appeared that the sample could be subdivided into three groups.
      The group of patients with relatively good results after active treatment showed
      less relapse than the group with relatively moderate results after active
      treatment. The patients with relatively good treatment results were mostly
      treated with extractions followed by fixed appliances in both jaws. This
      observation indicates that treatment planning in this group generally was
      correct. Patients showing skeletal Class II features before orthodontic treatment
      showed most relapse in overjet and overbite.

PMID- 12051176
TI  - [Facial and tooth injuries during the practice of sports].
AB  - The value of mouth protectors in the prevention of facial and dental injuries was
      investigated in seven different sports. 5300 sportsmen filled in a written
      questionnaire. The replies provided information on the number of facial and
      dental injuries that occur annually in the Netherlands. The use of mouth
      protectors was also recorded.

PMID- 12051177
TI  - NATO Advanced Workshop on Schizophrenia and Schizotypy. March 24-27, 2001,
      Tuscany, Italy. Proceedings of a conference in honor of Peter H. Venables.

PMID- 12051178
TI  - The write direction.

PMID- 12051179
TI  - Getting better. Interview by Dina Leifer.

PMID- 12051180
TI  - [Comment to the letter by V. Ia. Gindikin].

PMID- 12051181
TI  - Proceedings of the 12th International Hypoxia Symposia. March 2001, Alberta,
      Canada.

PMID- 12051182
TI  - Social and economic patterning of health among women. Proceedings of an
      international seminar organized by the Commission for International Cooperation
      in National Research in Demography (CICRED).

PMID- 12051183
TI  - Gas analysis of blood and ascitic fluid in patients with liver cirrhosis
      concurrent complications.

PMID- 12051184
TI  - From Elephants to AIDS. Essays in biology in honor of Roger V. Short: Papers from
      the Havenmeyer Foundation Symposium to celebrate the life and work of Professor
      Roger V. Short ScD, FRS. June 27-30, 2001. Port Douglas, Australia.

PMID- 12051185
TI  - Organ donation. Public Policy Statement, November 2000 (revised).

PMID- 12051186
TI  - Evaluating the performance of the hospital CEO.

PMID- 12051187
TI  - Choosing a mentor.

PMID- 12051188
TI  - Experiences of fears associated with pregnancy and childbirth: a study of 329
      pregnant women.
AB  - BACKGROUND: Women may experience a variety of fears in association with pregnancy
      and childbirth. The purpose of this study was to describe their objects, causes,
      and manifestations, and to identify factors associated with the fears. METHODS:
      The study sample comprised 481 pregnant women in western Finland, of whom 329
      (response rate 69) completed a questionnaire. It was developed on the basis of
      semi-structured interviews and previous studies and had a 4-point scale and a
      dichotomous scale. Data were subjected to rotated factor analysis, and sum
      variables were produced. The effects of various demographic variables were
      calculated using the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Of the 329
      respondents, 78 percent expressed fears relating to pregnancy, to childbirth, or
      to both. Specific fears concerned childbirth, the child's and mother's well
      being, health care staff, family life, and cesarean section. Causes of fears were
      negative mood, negative stories told by others, alarming information, diseases
      and child-related problems, and, in multiparas, negative experiences of previous
      pregnancy, childbirth, and baby's health and care; causes were significantly
      related to occupation. Fears were manifested as symptoms of stress, effects on
      everyday life, and a wish to have a cesarean section or to avoid pregnancy and
      childbirth; employment situation and elective cesarean section were the most
      important factors related to manifestation of fears. Parity and antenatal
      training were the most important variables related to objects of fears.
      CONCLUSIONS: Women's fears that are associated with pregnancy and childbirth can
      be explained by different factors. It is important for perinatal health
      caregivers to ask pregnant women about their feelings related to the current
      pregnancy, childbirth, and future motherhood, and to give women who express fears
      an opportunity to discuss them, paying special attention to primiparas and to
      multiparas with negative experiences of earlier pregnancies.

PMID- 12051189
TI  - Prevalence and persistence of health problems after childbirth: associations with
      parity and method of birth.
AB  - BACKGROUND: Awareness about the extent of maternal physical and emotional health
      problems after childbirth is increasing, but few longitudinal studies examining
      their duration have been published. The aim of this study was to describe changes
      in the prevalence of maternal health problems in the 6 months after birth and
      their association with parity and method of birth. METHODS: A population-based,
      cohort study was conducted in the Australian Capital Territory (ACT), Australia.
      The study population, comprising women who gave birth to a live baby from March
      to October 1997, completed 4 questionnaires on the fourth postpartum day, and at
      8, 16, and 24 weeks postpartum. Outcome measures were self-reported health
      problems during each of the three 8-week postpartum periods up to 24 weeks.
      RESULTS: A total of 1295 women participated, and 1193 (92) completed the study.
      Health problems showing resolution between 8 and 24 weeks postpartum were
      exhaustion/extreme tiredness (60-49), backache (53-45), bowel problems (37-17),
      lack of sleep/baby crying (30-15), hemorrhoids (30-13), perineal pain (22-4),
      excessive/prolonged bleeding (20-2), urinary incontinence (19-11), mastitis (15
      3), and other urinary problems (5-3). No significant changes occurred in the
      prevalence of frequent headaches or migraines, sexual problems, or depression
      over the 6 months. Adjusting for method of birth, primiparas were more likely
      than multiparas to report perineal pain and sexual problems. Compared with
      unassisted vaginal births, women who had cesarean sections reported more
      exhaustion, lack of sleep, and bowel problems; reported less perineal pain and
      urinary incontinence in the first 8 weeks; and were more likely to be readmitted
      to hospital within 8 weeks of the birth. Women with forceps or vacuum extraction
      reported more perineal pain and sexual problems than those with unassisted
      vaginal births after adjusting for parity, perineal trauma, and length of labor.
      CONCLUSIONS: Health problems commonly occurred after childbirth with some
      resolution over the 6 months postpartum. Some important differences in prevalence
      of health problems were evident when parity and method of birth were considered.

PMID- 12051190
TI  - [Vaccination. Hepatitis B].

PMID- 12051191
TI  - Acute hydrocephalus and hemocephalus in intracranial hemorrhage.

PMID- 12051192
TI  - High-dose trigeminal neuralgia radiosurgery associated with increased risk of
      trigeminal nerve dysfunction.

PMID- 12051193
TI  - Suprasellar meningiomas.

PMID- 12051194
TI  - The contributions of Otfrid Foerster (1873-1941) to neurology and neurosurgery.

PMID- 12051195
TI  - Optimal randomization strategies when testing the existence of a phylogeographic
      structure.

PMID- 12051196
TI  - Abstracts of the 17th National Congress of the Rumanian Society of Pneumology and
      the 2nd Congress of the International Union Against Tuberculosis and Lung
      Diseases, Europe Region. Bucharest, Rumania, 17-20 April 2002.

PMID- 12051199
TI  - Abstracts of the XVIII International Congress "The Fetus as a Patient". Budapest,
      Hungary, April 25-28, 2002.

PMID- 12051198
TI  - [International Day of Nursing. 12th of May is dedicated to family health nursing
      this time]].

PMID- 12051197
TI  - Derris (Lonchocarpus) urucu (Leguminosae) extract modifies the peritrophic matrix
      structure of Aedes aegypti (Diptera:Culicidae).
AB  - Aqueous suspension of ethanol extracts of Derris (Lonchocarpus) urucu
      (Leguminosae), collected in the state of Amazonas, Brazil, were tested for
      larvicidal activity against the mosquito Aedes aegypti (Diptera:Culicidae). The
      aim of this study was to observe the alterations of peritrophic matrix in Ae.
      aegypti larvae treated with an aqueous suspension of D. urucu extract. Different
      concentrations of D. urucu root extract were tested against fourth instar larvae.
      One hundred percent mortality was observed at 150 microg/ml (LC(50) 17.6
      microg/ml) 24 h following treatment. In response to D. urucu feeding, larvae
      excreted a large amount of amorphous feces, while control larvae did not produce
      feces during the assay period. Ultrastructural studies showed tha larvae fed with
      150 microg/ml of D. urucu extract for 4 h have an imperfect peritrophic matrix
      and extensive damage of the midgut epithelium. Data indicate a protective role
      for the peritrophic matrix. The structural modification of the peritrophic matrix
      is intrinsically associated with larval mortality.

PMID- 12051200
TI  - Abstracts of the 4th European Congress of Chemotherapy and Infection. Paris,
      France, 4-7 May 2002.

PMID- 12051201
TI  - Health Sciences in the Caribbean in the New Millennium. January 10-13, 2001.
      Trinidad and Tobago. Abstracts.

PMID- 12051202
TI  - Abstracts from the 10th World Congress on the Menopause. Berlin, Germany, June 10
      14, 2002.

PMID- 12051203
TI  - Abstracts of the 143rd Meeting of the Acoustical Society of America. Pittsburgh,
      Pennsylvania, USA. 3-7 June 2002.

PMID- 12051204
TI  - Abstracts of the XXIX International Congress of Ophthalmology. 21-25 April 2002,
      Sidney, Australia.

PMID- 12051206
TI  - Medicine, philosophy, and the medical humanities.

PMID- 12051205
TI  - Research in family medicine and general practice: are we there yet?

PMID- 12051207
TI  - Imagination and empathy in the consultation.

PMID- 12051208
TI  - Do we have enough 'injidents'?

PMID- 12051209
TI  - Continuity of care in general practice: a survey of patients' views.
AB  - BACKGROUND: It is not known how patients value continuity for different health
      problems. In addition, it is not clear how different types of patients value
      continuity. It has been argued, for example, that young and healthy individuals
      have different ideas about continuity from older people with chronic illnesses.
      More extensive exploration of patients' views and expectations on personal
      continuity is important as this may help to organise general practice better in
      the future. AIM: To explore patients' views on continuity of care in general
      practice and their relations to patient characteristics. DESIGN OF STUDY: Postal
      questionnaire survey. SETTING: Thirty-five general practices throughout The
      Netherlands. METHOD: A sample of 25 patients from each practice was sent a
      questionnaire. RESULTS: The response rate was 644/875 (74%). The percentage of
      patients feeling that it was important to see their personal doctor varied, from
      21% for a splinter in the eye, to 96% for discussing the future when seriousy
      ill. The main reasons for preference of their own general practitioners (GPs)
      were the GP's assumed better medical knowledge of the patient and understanding
      of the personal and family background. Multiple linear regression analysis (GLM)
      showed that patient characteristics could explain 10% to 12% of the variance in
      these views on personal continuity. CONCLUSION: The importance that patients
      attach to continuity of care depends on the seriousness of the conditions/facing
      them. Patients in The Netherlands desire a high level of personal care for
      serious conditions. Patient characteristics, such as age, sex, and frequency of
      visits to the GP influence views on continuity of care only to a minor extent.

PMID- 12051210
TI  - A comparison of research general practices and their patients with other
      practices--a cross-sectional survey in Trent.
AB  - BACKGROUND: When interpreting results of studies undertaken by research networks
      we need to know how representative volunteer practices and their registered
      patients are of the total population of practices and patients in their locality.
      AIM: To compare the following in research and non-research general practices in
      one region: practice and population demography, morbidity and mortality, selected
      performance indicators, and health outcomes. DESIGN OF STUDY: Cross-sectional
      survey. SETTING: Sixty-six Trent Focus Collaborative Research Network general
      practices and 749 other general practices in Trent, United Kingdom. METHOD:
      Practice characteristics and GP contract data were obtained from the NHS
      Executive, Quarry House, Leeds. The Trent Regional NHS Hospital Admission
      Database was searched to identify all relevant admissions to hospital from all
      practices between 1 April 1993 and 31 March 1997. Ward-linked data on cancer were
      obtained from the Trent Cancer Registry. RESULTS: Of the 815 general practices in
      Trent Region in the study period, 66 (8%) were in the Trent Focus network. They
      were more likely to be involved in training GPs and to have a female partner.
      They tended to be larger, with fewer single-handed doctors and younger GPs.
      Network practices prescribed a higher proportion of generics (median %
      prescribed/practice = 70%, versus 51%, Mann-Whitney U = 1615, P<0.0001). There
      were no clinically important differences between hospital admission rates between
      the two groups or waiting times for surgical procedures. There was no difference
      in the incidence of cancer and standardised mortality ratios related to the
      electoral wards of the GP surgery. CONCLUSION: Although there were differences in
      practice structure and some aspects of performance, we found no important
      differences in the demography of registered patients, nor in morbidity,
      mortality, or access to or use of secondary care.

PMID- 12051211
TI  - Radiography for low back pain: a randomised controlled trial and observational
      study in primary care.
AB  - BACKGROUND: Lumbar spine radiography has limited use in diagnosing the cause of
      acute low back pain. Consensus-based guidelines recommend that lumbar spine x
      rays are not used routinely. However there have been no studies of the effect of
      referral for radiography at first presentation with low back pain in primary
      care. AIM: To compare short and long-term physical, social, and psychiatric
      outcomes for patients with low back pain who are referred or not referred for
      lumbar spine x-ray at first presentation in general practice. DESIGN OF STUDY: A
      randomised unblinded controlled trial with an observational arm to enable
      comparisons to be made with patients not recruited to the trial. SETTING: Ninety
      four general practices in south London and the South Thames region. METHOD:
      Patients consulting their general practitioner (GP) with low back pain at first
      presentation were recruited to a randomised controlled trial (RCT) or to an
      observational group. Patients in the trial were randomly allocated to immediate
      referral for x-ray or to no referral. All patients were asked to complete
      questionnaires initially, and then at six weeks and one year after recruitment.
      RESULTS: Six hundred and fifty-nine patients were recruited over 26 months: 153
      to the randomised trial and 506 to the observational arm. In the RCT referral for
      x-ray had no effect on physical functioning, pain or disability, but was
      associated with a small improvement in psychological wellbeing at six weeks and
      one year. These findings were supported by the observational study in which there
      were no differences between the groups in physical outcomes after adjusting for
      length of episode at presentation; however, those referred for x-ray had lower
      depression scores. CONCLUSIONS: Referral for lumbar spine radiography for first
      presentation of low back pain in primary care is not associated with improved
      physical functioning, pain or disability. The possibility of minor psychological
      improvement should be balanced against the high radiation dose involved.

PMID- 12051213
TI  - How successfully do general practitioners diagnose herpetic gingivo-stomatitis
      clinically?
AB  - Herpetic gingivo-stomatitis is a common, often painful affliction of young
      children. Recently, aciclovir treatment has been found to be effective in
      hospital-referred cases, an approach limited in general practice where laboratory
      diagnosis is invariably impractical. This study demonstrated that 49 out of 63
      clinical diagnoses of herpetic gingivo-stomatitis [PPV = 78%] made by 27 GPs were
      subsequently validated by laboratory virus culture. This suggests that herpetic
      gingivo-stomatitis might be treated with aciclovir in general practice on the
      basis of a clinical diagnosis alone.

PMID- 12051212
TI  - Primary care referrals for lumbar spine radiography: diagnostic yield and
      clinical guidelines.
AB  - BACKGROUND: Primary care requests for radiographs of the lumbar spine have come
      under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by
      limiting referrals to patients at high risk of serious disease have been widely
      distributed. Trial evidence suggests that guidelines can reduce radiography
      referrals. It is not clear whether this reduction has been achieved in routine
      practice. AIM: This study, using routine data, was conducted to measure trends in
      pnmary care referrals for lumbar spine radiography at two hospitals between 1994
      and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine
      radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge
      (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30
      June 1999), United Kingdom. METHOD: All primary care requests for lumbar
      radiography were identified electronically from computerised information systems.
      A random sample of 2100 radiography reports were classified according to clinical
      importance. These classifications were used to examine whether the proportion of
      radiographs demonstrating potentially more serious findings had increased between
      1994 and 1999. RESULTS: There was no evidence that primary care referrals for
      radiography of the lumbar spine had decreased between 1994 and 1999 at either
      hospital. General practitioners did not progressively refer more high-risk
      patients for lumbar radiography. Only a small proportion of patients had
      important radiographic findings that might warrant specialist referral or
      specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers
      much to the NHS. However in these two hospitals, the reduction in radiograph
      utilisation evident in trials was not achieved. Guideline development is a
      resource intensive process; distribution must be supported by more effective
      implementation strategies.

PMID- 12051214
TI  - A randomised comparison of the effect of three patient information leaflet models
      on older patients' treatment intentions.
AB  - One hundred and ninety-six patients over the age of 65 years suffering from joint
      pain were randomised to receive one of three patient information leaflets
      describing a hypothetical pain medication, a standard textual patient information
      leaflet (PIL) given out by a pharmaceutical chain, and two alternate-forms
      depicting information with icons and graphs. The results showed that patients
      randomised to the traditional PIL were less likely to consider taking the
      hypothetical medication.

PMID- 12051215
TI  - How can we develop a cost-effective quality cervical screening programme?
AB  - This article discusses the evidence base underpinning the United Kingdom cervical
      screening programme and proposes that there is now sufficient evidence to suggest
      that too many women are screened too frequently. The financial savings generated
      from increasing the screening interval to five years and restricting routine
      screening to women aged 25 to 50 years may, we suggest, be better spent on
      improving the quality of the cervical screening programme. Re-awakening this
      debate must not however deflect energy and effort from recruiting women who have
      never been screened or further developing quality control systems. Any debate
      must also fully engage women of all ages as the key stakeholders in the decision
      making process.

PMID- 12051216
TI  - The clinical diagnosis of acute purulent sinusitis in general practice--a review.
AB  - Acute sinusitis is a common illness in primary care. Studies have demonstrated
      the difficulty of making the differential diagnosis of acute purulent sinusitis
      based on clinical evaluations alone. This leads to a significant overuse of
      antibiotics, which in turn may contribute to increased bacterial resistance. In
      most cases, GPs have to base their differential diagnosis of sinusitis on
      clinical signs and symptoms and examination of the patient. The aim of this
      review is to assess which clinical signs and symptoms can predict an acute
      purulent sinusitis, compared with accepted reference standards. A review of the
      literature was performed by looking at articles related to the diagnoses of acute
      sinusitis in general practice. The following search criteria were used:
      unselected general practice population; objective reference standard; and
      logistic regression to evaluate symptoms and signs independently associated with
      the diagnosis. Four studies were identified for further analysis. The following
      symptoms and signs were associated with acute purulent sinusitis: purulent
      secretion as a symptom experienced by the patient or as a sign demonstrated in
      the nasal cavity by the doctor; pain in the teeth; pain at bending forward, and
      two phases in the illness history. An elevated erythrocyte sedimentation rate and
      increased C-reactive protein also contributed to the diagnosis. By use of the
      specified signs and symptoms the GP can increase the probability of correctly
      diagnosing an acute purulent sinusitis and reserve antibiotic prescription for
      these patients.

PMID- 12051217
TI  - Osteoporosis in postmenopausal women.

PMID- 12051218
TI  - Osteoporosis in postmenopausal women.

PMID- 12051219
TI  - Haematuria.

PMID- 12051220
TI  - Haematuria.

PMID- 12051222
TI  - Mortality in general practice.

PMID- 12051221
TI  - Current issues in fitness for work certification.

PMID- 12051223
TI  - Restricting the use of thioridazine.

PMID- 12051224
TI  - Bladder catheterisation.

PMID- 12051225
TI  - Prescribing costs and patterns.

PMID- 12051226
TI  - Telephone consultations.

PMID- 12051227
TI  - Telephone consultations.

PMID- 12051228
TI  - Telephone consultations.

PMID- 12051229
TI  - Impotence in Europe.

PMID- 12051230
TI  - Viewpoint 2--GPs and child protection: time to grasp the nettle.

PMID- 12051231
TI  - Oral history and qualitative research.

PMID- 12051232
TI  - An oral history of everyday general practice: speaking for a change.

PMID- 12051234
TI  - Hype and spin in the NHS.

PMID- 12051233
TI  - Practical reasoning and decision making--Hippocrates' problem, Aristotle's
      answer.

PMID- 12051235
TI  - The expert patient.

PMID- 12051236
TI  - They'd have made good GPs.

PMID- 12051238
TI  - Abstracts of the Biennial Meeting of the International Association for the Study
      of the Liver, April 15-16, 2002 and the 37th Annual Meeting of the European
      Association for the Study of the Liver, April 18-21, 2002. Madrid, Spain.

PMID- 12051237
TI  - The European definitions of the key features of the discipline of general
      practice: the role of the GP and core competencies.

PMID- 12051240
TI  - ISEH 2002. 31st Annual Meeting of the International Society for Experimental
      Hematology. Montreal, Canada, July 5-9, 2002. Abstracts.

PMID- 12051239
TI  - Abstracts of the Teratology Society 42nd Annual Meeting. June 22-27, 2002.
      Scottsdale, Arizona, USA.

PMID- 12051241
TI  - Abstracts of the American Spinal Injury Association 28th Annual Scientific
      Meeting. May 3-6, 2002. Vancouver, British Columbia, Canada.

PMID- 12051242
TI  - Acute management of autonomic dysreflexia: individuals with spinal cord injury
      presenting to health-care facilities.

PMID- 12051243
TI  - The authority of human nature: the Schadellehre of Franz Joseph Gall.
AB  - This essay is the first account in English to examine Franz Joseph Gall and the
      origins of phrenology. In doing so a host of legends about Gall and the
      beginnings of phrenology, which exist only in the English-language
      historiography, are dispelled. An understanding of the context of phrenology's
      origins is essential to to the historicization of the movement as a whole. The
      first of two sections in the essay, therefore, introduces Gall's biography and
      the context in which his provocative science emerged. It is shown to what extent
      Gall borrowed from other thinkers of his time. I show that Gall's system was
      meant to be a certain science of human nature. In the second section I analyse
      the reactions of contemporaries to Gall's important two-year lecture tour of
      Europe. I conclude that although many critics dismissed Gall as a charlatan,
      there was no consensus about the proper way to disseminate scientific knowledge
      or the attributes necessary for the gentleman of science. For example, it was not
      clear whether science could be profitable, whether it should be shared with lay
      audiences or whether it could in fact be science at all if it was also
      entertaining. I argue that in any case Gall's aim was never really to impart
      science or to disseminate his system. His science and early means of
      disseminating it were meant to generate elite intellectual status. In this Gall
      was quite successful.

PMID- 12051244
TI  - What is the best initial therapy for the average patient with idiopathic
      achalasia?

PMID- 12051245
TI  - [Hospitals in central France].

PMID- 12051246
TI  - [The hospital of Marcigny (Saone-et-Loire)].

PMID- 12051247
TI  - [Early hospitals in Belgium].

PMID- 12051248
TI  - [The hospital of Alise - Sainte-Reine].

PMID- 12051249
TI  - Putting method first: re-appraising the extreme determinism and hard
      hereditarianism of Sir Francis Galton.

PMID- 12051250
TI  - Religion and medicine in Iran: from relationship to dissociation.

PMID- 12051251
TI  - Managing Medicaid in tough times.
AB  - States are struggling with soaring Medicaid costs. Some are using short-term
      solutions, others have launched bold reforms.

PMID- 12051252
TI  - Conviction for addiction: states are reconsidering whether no-nonsense drug
      policy should mean prison or treatment.

PMID- 12051254
TI  - How to stop a silent killer: colorectal cancer screening.

PMID- 12051253
TI  - Do fetal rights limit mothers' rights?

PMID- 12051255
TI  - Judge says feds can't usurp state in assisted suicide.

PMID- 12051256
TI  - Medievalists and the study of childhood.

PMID- 12051257
TI  - From famine to Five Points: Lord Lansdowne's Irish tenants encounter North
      America's most notorious slum.

PMID- 12051258
TI  - The metaphoric circuit: organic and technological communication in the nineteenth
      century.

PMID- 12051259
TI  - Science and statistical victim: modernizing knowledge in breast implant
      litigation.
AB  - The advent of mass torts in US federal courts in the latter third of the 20th
      century accelerated a process of modernization in an institution that was
      unprepared for standardized approaches to dispute resolution. Faced with large
      scale technological disasters, in particular, courts struggled to reform both
      their procedures and their fact-finding approaches in order to deal with multiple
      claimants in consolidated proceedings. Using silicone gel breast implant
      litigation as a case study, this paper argues that the attempt to marry judicial
      concerns for individual justice with administrative concerns for speed,
      efficiency and economy has produced anomalous results. The testimony of the
      clinician and the victim has become less relevant as judicial remedies take
      account of injuries done to classes of plaintiffs. Subjective claims about the
      body are subordinated to statistical correlations between exposure and grouped
      complaints. At the same time, the transfer of fact-finding authority from juries
      to judges under new evidentiary rules has privileged the judiciary's lay
      knowledge and experience over that of the jury. While these transformations may
      hasten the processing of cases, the paper questions whether the courts can
      legitimately take on board the issues of risk and social justice in contemporary
      industrial societies.

PMID- 12051260
TI  - The realness of risk: gene technology in Germany.
AB  - This paper examines the material relations of risk within a dispute about the
      hazards of manufacturing human insulin using gene technology, and the role played
      by the referent 'real risk' in the technical performance of risk in that dispute.
      It draws on recent work in science and technology studies that extends actor
      network theory to examine the performance of reality in scientific practice. The
      multiplicity of risks in the dispute, and the links made and unmade between them,
      are examined. I argue that in the dispute, risks were contingently linked and
      separated around a referent 'real risk' that emerged within the recombinant DNA
      debate of the late 1970s. I contrast my account of risk with realist and
      relativist accounts, each of which values risk as an abstract entity. In my
      account, risk's value is contingent upon sets of material relations that link
      hazards and procedures for their minimization. Risk's realness emerges as some
      risks are linked and others separated, working a multiple/singular relation in an
      ontological politics of risk.

PMID- 12051261
TI  - Methadone: six effects in search of a substance.
AB  - What is the difference between heroin and methadone? Is this difference one of
      interpretation, where an 'opiate-like' substance is 'labelled' differently
      through social processes that arbitrarily describe methadone as 'legal' and
      'therapeutic', and heroin as 'illegal' and 'harmful'? To study the nature of this
      difference, I follow two experiments in the United States and in France of
      methadone substitution, where medical practices attempt to replace heroin by
      methadone, and thereby to reduce the user's (illegal) drug use. In these trials,
      the experimenters ask precisely this question. The question of the nature of the
      difference between the substance's actions is further illustrated by the
      comparison between the substitution trials: when the experimenters describe
      methadone differently in different places and times, do they 'interpret' the drug
      differently, or is the drug itself different? I show that far too many elements
      vary from trial to trial to say that the 'interpretation' of the substance is all
      that varies. In order to explore the variation in detail, then, I draw on works
      about 'performance', and on the actor-network 'theory of action': what heroin and
      methadone do, but also also the very way in which they 'pass into action', is
      what varies in each trial. In the end, this question about difference is a
      question about action. In each trial, there is not from the start one substance
      with fixed or vague properties which one can then interpret in various manners.
      'Substance' does not contain inherent actions from the start ('properties').
      Rather, following the experimenters, it is possible to say that 'effects' are
      primary and that only at the end of the trial do the experimenters laboriously
      'find substance' to effects.

PMID- 12051262
TI  - The truth about dieting.

PMID- 12051263
TI  - Oral contraceptives and the risk of myocardial infarction.

PMID- 12051264
TI  - Oral contraceptives and the risk of myocardial infarction.

PMID- 12051265
TI  - Oral contraceptives and the risk of myocardial infarction.

PMID- 12051266
TI  - Oral contraceptives and the risk of myocardial infarction.

PMID- 12051267
TI  - Diabetes prevention.

PMID- 12051268
TI  - Diabetes prevention.

PMID- 12051269
TI  - Diabetes prevention.

PMID- 12051270
TI  - BIOIRON 2001 World Congress on Iron Metabolism. August 18-23, 2001. Cairns,
      Australia. Abstracts.

PMID- 12051271
TI  - [Fritz Blumenstein, 1898-1993: life of a leading German dentist].

PMID- 12051272
TI  - [The Basler collection of recipes: studies in late medieval German cookbooks].

PMID- 12051273
TI  - [Mendelism in animal breeding as developed by professor Leopold Frateur, Louvain
      (1877-1946)].
AB  - Educated as a veterinarian at Cureghem, Leopold Frateur started his scientific
      career in 1899 as a professor at the Faculty of Sciences of the Catholic
      University of Louvain, Belgium, in charge of the course in zootechnology. After a
      study tour to zootechnical institutes and centres of animal breeding in Europe he
      was invited by the governmental department of Agriculture and the Belgian Society
      of Zootechnology to investigate the relevance of the Mendelian laws of heredity
      for the improvement of cattle breeding. In the early years of the century,
      Frateur conducted field research in order to determine the characteristics of the
      cattle breeds in Belgium. In 1908 Frateur founded the Institute of Animal
      Husbandry at his university. Here he worked out his programme of experimental
      genetics until his retirement in 1936. The last six years of his professorship he
      teached also agricultural economics in the Faculty of Economical Sciences. In
      Frateur's experimental research the following main lines can be distinguished: 1)
      The analysis of simple and complex hereditary factors in cattle, rabbits and
      poultry; 2) The study of qualitative and quantitative characteristics of
      importance for the improvement of animal breeds; 3) The synthesis of genetic
      factors from different stock in order to obtain higher yielding breeds with
      stable characteristics; 4) Theoretical study of the relationship between genotype
      and phenotype and the influence of environment factors; 5) Theoretical
      exploration of the issue of variability and modification of newly formed
      characteristics; 6) Research leading to an explanation of telegony and atavism;
      7) The formulation of a theory on the creation of new breeds in domestic animals
      and plants, and the relation between breed and species. Also he was responding to
      topical needs, e.g. he determined the causal factor of pullorum epidemic in
      chicken farming, or he investigated the hereditary resistance against diphteric
      infection amongst chickens. Frateur took the theoretical knowledge on heredity as
      the starting point for practical application in cattle breeding. During and right
      after W. W. I. he stated that the current scientific knowledge is enough advanced
      to consider the start of a large breeding programme for the improvement of cattle
      livestock. In order to realise this reinstatement Frateur received important
      support from the authorities (Royal Decree, August 1919). From then onwards he
      focussed his efforts on the realisation of a national framework for improvement
      of cattle livestock, in collaboration with regional centres and societies for
      animal selection, breeding and production. Later he also started programmes for
      the improvement of chicken and pig breeding, again in a joint effort with
      official consultants and members of breeding societies. He was not only the
      architect of these programmes, providing the necessary scientific and technical
      guidance, but he had also a chair in the governing bodies, supervising the
      execution and control of the breeding programmes. In order to draw a picture of
      the research community engaged in animal breeding during the first decennia of
      the 20th century Frateur's contacts through study tours, congresses and learned
      societies are investigated. The life and work of Frateur is described by the
      author in two volumes, published in 1999. The second volume consists of a reprint
      of 50 selected papers on animal breeding.

PMID- 12051274
TI  - Gender and veterinary medicine: global historical perspectives.
AB  - This essay will suggest research methodologies for historians interested in the
      history of gender and veterinary medicine over the past 200 years. This topic is
      a very timely one, because we are currently living through a transition in the
      interactions between gender and veterinary medicine. Traditionally male
      dominated, veterinary medicine has recently experienced a world-wide increase in
      the number of women entering veterinary schools and practicing in all areas of
      the profession. Understanding this transition requires us to ask historical,
      cultural, and sociological questions in order to illuminate the roles of gender
      ideologies and the participation of women in the development of modern veterinary
      medicine. The following paragraphs outline three specific methodological
      strategies that historians have used to study the interactions between gender and
      science and gender and medicine. I will propose ways that we veterinary
      historians can use these strategies to study gender and veterinary medicine. It
      is beyond the scope of this paper to summarize the literature on women and
      veterinary medicine; but it will nonetheless highlight a few studies from nations
      around the world to illustrate the methodological strategies that I propose. I
      hope to provide scholars with ideas for future studies in the history of gender
      and veterinary medicine.

PMID- 12051275
TI  - Assessment of local pulse wave velocity in arteries using 2D distension
      waveforms.
AB  - The reciprocal of the arterial pulse wave velocity contains crucial information
      about the mechanical characteristics of the arterial wall but is difficult to
      assess noninvasively in vivo. In this paper, a new method to assess local pulse
      wave velocity (PWV) is presented. To this end, multiple adjacent distension
      waveforms are determined simultaneously along a short arterial segment, using a
      single 2D-vessel wall tracking system with a high frame rate (651 Hz). Each B
      mode image consists of 16 echo lines spanning a total width of 15.86 mm.
      Dedicated software has been developed to extract the end-diastolic diameter from
      the B-mode image and the distension waveforms from the underlying radiofrequency
      (rf) information for each echo-line. The PWV is obtained by determining the ratio
      of the temporal and spatial gradient of adjacent distension velocity waveforms.
      The proposed method is verified in a phantom and in the common carotid artery
      (CCA) of humans. Phantom experiments show a high concordance between the PWV
      obtained from 2D distension velocity waveforms (4.21 +/- 0.02 m/s) and the PWV
      determined using two pressure catheters (4.26 +/- 0.02 m/s). Assuming linear
      spatial gradients, the PWV can also be obtained in vivo for CCA and averages to
      5.5 +/- 1.5 m/s (intersubject variation, n = 23), which compares well to values
      found in literature. Furthermore, intrasubject PWV compares well with those
      calculated using the Bramwell-Hill equation. It can be concluded that the PWV can
      be obtained from the spatial and temporal gradient if the spatial gradient is
      linear over the observed length of the artery, i.e. the artery should be
      homogenous in diameter and distension and the influence of reflections must be
      small.

PMID- 12051276
TI  - Tradeoffs in elastographic imaging.
AB  - This paper presents the tradeoffs in elastographic imaging. Elastography is
      viewed as a new imaging modality and presented in terms of three fundamental
      concepts that constitute the basis for the elastographic imaging process. These
      are the tissue elastic deformation process, the statistical analysis of strain
      estimation and the image characterization. The first concept involves the use of
      the contrast transfer efficiency (CTE) that describes the mapping of a
      distribution of local tissue elastic moduli into a distribution of local
      longitudinal tissue strains. The second concept defines the elastographic system
      and the relationship between ultrasonic and signal processing parameters. This
      process is described in terms of a stochastic framework (the strain filter) that
      provides upper and practical performance bounds and their dependence on the
      various system parameters. Finally, the output image, the elastogram, is
      characterized by its image parameters, such as signal-to-noise ratio, contrast-to
      noise ratio, dynamic range and resolution. Finite-element simulations are used to
      generate examples of elastograms that are confirmed by the theoretical prediction
      tools.

PMID- 12051277
TI  - Vibro-acoustography: quantification of flow with highly-localized low-frequency
      acoustic force.
AB  - The intersection of two ultrasound beams with slightly different frequencies
      results in generation of a localized radiation force and stimulates emission of
      audio signals from targeted objects. Vibro-acoustography uses this phenomenon to
      probe elastic properties of objects. Vibro-acoustography of contrast microbubbles
      in degassed water produced quantitative flow measurements from analysis of their
      acoustic emission. We used a dual-beam transducer generating bursts of 40-kHz
      vibrations. The vibrations resulted from interference of 3.48-MHz and 3.52-MHz
      confocal beams intersecting at the center of a thin plastic conduit. We tested
      flows of 13,48, 85, and 120 mL/min of contrast microbubbles at concentrations
      from 1.2 x 10(5) to 6 x 10(9) bubbles/mL. The amplitude of the acoustic emission
      was linear with microbubble concentrations up to a value of 3.6 x 10(5)
      bubbles/mL. A replenishment method for microbubble contrast and flow rate
      analysis was used with radiation force bursts deployed at 0.05, 0.1, 0.2, (.5, 1,
      and 2-second pulsing intervals. The relation between the pulsing intervals and
      the peak amplitude was fitted by an exponential curve and a rate constant
      calculated for each tested flow rate. The rate constant values were linearly
      correlated with the tested flows. The vibro-acoustography method provides
      objective, quantitative, and highly-localized assessment of flow using contrast
      microbubbles.

PMID- 12051278
TI  - An ophthalmologist's approach to visual processing/learning differences.

PMID- 12051279
TI  - Efficacy of induction chemotherapy in retinoblastoma, alone or combined with
      other adjuvant modalities.
AB  - BACKGROUND: There are not much data available on the use of newer antimetabolites
      as an initial treatment modality in retinoblastoma, or their effect on vitreous
      seedings and de novo foci, especially in the Indian subcontinent. METHODS: To
      evaluate the efficacy of newer agents as induction chemotherapy, 34 tumors in 22
      eyes of 19 children with bilateral retinoblastoma were treated with 2 cycles of
      carboplatin, etoposide, vincristine, and cyclophosphamide; each cycle was of 1
      month duration. The tumor response was evaluated at 2 months and adjuvant salvage
      modalities (ie, cryotherapy, laser, and/or external beam radiotherapy) were added
      as needed. The cycles were continued and ophthalmoscopic and ultrasonographic
      monitorings were performed to determine further tumor response, tumor height
      regression, effect on vitreous seeds, and other ocular changes. RESULTS: Mean
      tumor height at presentation was 4.2 mm, which regressed to 2.61 mm at 6 months
      (P=0.000). The biggest tumor to respond was 12.5 mm, although smaller multiple
      tumors regressed better. Adjuvant modalities were used in 28 tumor foci in 16
      eyes. A follow up of 6 to 24 months (mean, 12.8+/-6.21 months), showed complete
      regression in 12/34 tumors, partial regression in 15/34, stable disease in 6/34,
      and 1 tumor progressed despite all therapy. Results in all 6 eyes with vitreous
      seeds were most gratifying; at 1 year vitreous seeds disappeared in 4 eyes and
      showed complete calcification in 2. Fresh new lesions were not seen in any eye
      with complete response after the first 2 cycles of chemotherapy. Recurrences were
      nil and complications minor. CONCLUSIONS: The overall tumor response (complete
      and partial) of more than 80% indicates that chemoreduction is an effective
      modality alone and combined with adjuvant salvage modalities. The results with
      our treatment regime, even in cases with advanced intraocular retinoblastoma, are
      encouraging.

PMID- 12051280
TI  - No clinical correlation between bilirubin levels and severity of retinopathy of
      prematurity.
AB  - PURPOSE: To evaluate the hypothesis that bilirubin has a protective effect
      against the development of severe retinopathy of prematurity (ROP). METHODS: An
      assessment of 76 infants born at 24 and 25 weeks' gestation and admitted to the
      level III neonatal intensive care unit at Saitama Children's Medical Center was
      made. Indirect ophthalmoscopy fundus examinations were performed on all infants
      to identify the degree and progression to threshold ROP. We analyzed the daily
      bilirubin levels and grouped the patients according to the severity of ROP based
      on the infant's worst ROP examination. The first group was comprised of infants
      with less than stage 3 ROP and infants with stage 3 ROP. The second group was
      infants with less than prethreshold ROP or prethreshold ROP, and infants with
      threshold ROP. Next, we divided the infants into 3 groups: less than prethreshold
      ROP, prethreshold ROP, and threshold ROP. The daily changes in serum bilirubin
      concentrations during the first 14 days of life were determined for each infant.
      Three groups (less than prethreshold ROP, prethreshold ROP, and threshold ROP)
      were comparable as to their basic data, clinical characteristics, and treatments.
      RESULTS: ROP was found in 76 infants. There were no statistical differences in
      the clinical characteristics and treatments, excluding the duration of
      phototherapy, among the 3 groups. During the first 14 days of age, there were no
      significant differences in the daily mean bilirubin concentrations according to
      the groups separated by severity of ROP. CONCLUSION: These results indicate that
      there is no distinct protective effect of bilirubin on the development of severe
      ROP.

PMID- 12051281
TI  - Ocular outcomes in low birth weight premature infants with intraventricular
      hemorrhage.
AB  - PURPOSE: To study ocular outcomes in very low birth weight premature infants with
      intraventricular hemorrhage. METHODS: Parents of 490 consecutive very low birth
      weight (less than 1500 g) premature infants who were discharged from the neonatal
      intensive care unit of our hospital between 1994 and 1996 were asked to enroll
      their child/children in this cross-sectional study. Sixty infants (12%) were
      recruited and had complete masked ophthalmologic examinations at 12 months
      corrected gestational age. The medical records of each infant were reviewed after
      the eye examination was complete. The occurrence of intraventricular hemorrhage
      and other perinatal comorbidities was documented. Ocular outcomes of infants with
      no or low-grade (grades I-II) hemorrhages were compared with those of infants
      with high-grade (grades III-IV) intraventricular hemorrhage. RESULTS: Of the 60
      infants examined, 17 (28%) had neonatal intraventricular hemorrhage. Eleven (18%)
      had high-grade intraventricular hemorrhage, and 49 (82%) had no or low-grade
      hemorrhage. Of the 11 infants with high-grade intraventricular hemorrhage, 8
      (73%) had strabismus compared with 7 (14%) of 49 infants with no or low-grade
      hemorrhages who developed strabismus (P<0.001). The high-grade group also had a
      larger proportion of infants with ocular motility defects (P=0.008), nystagmus
      (P<0.001), optic nerve atrophy (P<0.001), and abnormal retinal findings
      (P=0.039). Additionally, these infants were more likely to have stage 3 or worse
      retinopathy of prematurity (P=0.003). CONCLUSIONS: These results confirm the
      findings of our earlier retrospective study, and suggest that the occurrence of
      high-grade intraventricular hemorrhage in the early postnatal period places these
      infants at significant risk for adverse ocular outcomes. These infants require
      close ophthalmologic surveillance.

PMID- 12051283
TI  - Management of infantile abduction deficits.

PMID- 12051282
TI  - Comparative evaluation of diclofenac and dexamethasone following strabismus
      surgery.
AB  - PURPOSE: To compare efficacy of topical diclofenac sodium 0.1% with dexamethasone
      0.1% following strabismus surgery. METHODS: In this study, 58 patients undergoing
      strabismus surgery were evaluated. They were randomized into two groups: 29
      patients received topical 0.1% diclofenac (Group A), and 29 patients received
      0.1% dexamethasone (Group B) for 4 weeks. The baseline parameters were similar in
      both groups. At each visit comprehensive ocular examination was performed to
      record patient discomfort, conjunctival inflammation, gap, and intraocular
      pressure. Follow-up visits were at 1 week, 2 weeks, and 4 weeks, postoperatively.
      RESULTS: There was no statistically significant difference in the rate of
      resolution of the inflammation, conjunctival healing, and intraocular pressure
      except rise of intraocular pressure at the fourth postoperative week in group B
      (P value <0.001). CONCLUSIONS: The results of this study suggest that diclofenac
      may be used as an alternative to dexamethasone after strabismus surgery.

PMID- 12051284
TI  - Slippage of lateral rectus muscle following surgery for esotropia: an occult
      complication?

PMID- 12051285
TI  - Retinoblastoma presenting as panophthalmitis: clinicopathological study of a
      case.

PMID- 12051286
TI  - Ophthalmia neonatorum associated with isoimmune neonatal neutropenia.

PMID- 12051287
TI  - Bilateral subperiosteal orbital hematomas in a child with sickle cell disease.

PMID- 12051288
TI  - Pediatric Horner's syndrome due to a cervical thymic rest.

PMID- 12051290
TI  - Biological functions of blood groups in health and disease.
AB  - Biochemical studies reveal that erythrocyte blood group antigens are the
      immunological expression of polymorphic and, frequently, biologically-active
      membrane structures. Some of these structures have been identified to be specific
      transport proteins, enzymes, or receptors for infectious agents. Certain
      erythrocyte phenotypes, for example, Rh(null), lack all or most antigens in a
      specific blood group system. Changes in erythrocyte morphology and function
      associated with these phenotypes provide insights into the roles of the
      corresponding proteins in the maintenance of membrane integrity. Other
      phenotypes, for example Oh, and p, also lack multiple blood group antigens, but
      the absence of changes in morphology or function in these erythrocytes suggests
      that their corresponding carbohydrate determinants are not essential for
      maintaining membrane integrity. Additional information on the function of
      erythrocyte membrane structures that express blood group antigens is likely to
      advance our understanding of the role of blood groups in health and disease.

PMID- 12051289
TI  - Aplasia of the optic chiasm and tracts with unifocal polymicrogyria in an
      otherwise healthy infant.

PMID- 12051291
TI  - Beta-thalassaemia and the prevalence of HCV viraemia.
AB  - Twenty-four serum samples from multitransfused patients with beta-thalassaemia
      major and fourteen positive control samples, (eight haemodialysis patients and
      six sporadic cases of HCV infection) were selected as anti-HCV-positives by a
      second-generation ELISA, a confirmatory test (Abbott), and an immunoblot assay
      (INNO-LIA HCV AbIII, Omicron Medical). Subsequently, by means of the nested
      polymerase chain reaction technique (PCR), using the set of PT1-4 primers, the
      RNA of the virus was detected in a total of 29 samples: 22 out of 24 patients
      with beta-thalassaemia and 7 out of 14 from the control group were positive for
      the RNA of the virus. The findings show that there is a statistically significant
      prevalence [chi2 = 6.344, P < or = 0.02] of HCV viraemia in the population of
      beta-thalassaemia major in Greece, as compared with the positive control group.

PMID- 12051292
TI  - Secondary myelodysplastic syndromes and acute leukemias.
AB  - Secondary myelodysplastic syndrome (sMDS) and secondary acute leukemia (sAL) are
      hematologic neoplasms occurring a few years following another primary malignancy,
      and are believed to be related to the chemotherapy used for the primary disease.
      Alkylating agents are considered to be more leukemogenic than other
      chemotherapeutic agents. Hodgkin's disease and multiple myeloma, among the
      hematologic neoplasms, and breast cancer among the solid tumors, are associated
      with this late complication more than other malignancies. The clinical picture is
      similar to primary MDS. However, the course is rapid, with early leukemic
      transformation and poor prognosis. since many sMDS patients are relatively young,
      it is reasonable to suggest an aggressive approach, i.e. bone-marrow
      transplantation (BMT) or antileukemic chemotherapy. The older patients may be
      offered low dose ara-c (LDAC), differentiating agents or clinical trials with
      growth factors. Even the responders survive no more than a few months.

PMID- 12051293
TI  - Extramedullary haemopoiesis in thalassaemia intermedia: an unusual case of
      relapsing paraparesis in pregnancy.
AB  - We report a case of thalassaemia intermedia complicated during two consecutive
      pregnancies by two episodes of spastic paraparesis due to compression of the
      spinal cord by extramedullary paravertebral masses. The patient was successfully
      treated by hypertransfusion and local irradiation. Compression of vital organs by
      the extramedullary masses must always be considered in chronic haemolytic
      anaemias during periods of increased haemopoietic demands like pregnancy. As
      relapses can not be excluded, a closer follow-up is needed. A dose of irradiation
      preventing from recurrences in the same anatomical area, seems necessary.

PMID- 12051294
TI  - Histological and functional changes in the salivary glands in thalassaemia major.
AB  - Oral salivary secretion and oral histology in 15 multi-transfused adult
      thalassaemia homozygotes was studied. Iron stores of minor salivary glands were
      also histochemically determined. Salivary secretion in multi-transfused
      thalassaemia patients was subclinically decreased, but no clear correlation was
      evident between salivary secretion impairment and salivary gland destruction by
      iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism
      remains to be determined.

PMID- 12051295
TI  - Safer haemotherapy: the responsibilities of government, transfusion service,
      blood donors, and physician-users.
AB  - Despite the introduction of new selection, screening and quality assurance
      procedures, transfusion of allogeneic blood or blood products is not without
      risk. Iatrogenic bacterial or viral infection and incompletely understood
      immunological effects remain major concerns. Close communication and cooperation
      between the major players on the blood transfusion team - government, transfusion
      service, blood donors, and physician-users - are essential if new developments
      and technology are to lead to safer and more efficacious haemotherapy.

PMID- 12051296
TI  - Bactericidal capability of blood platelets in eutrophic newborns.
AB  - Bactericidal activity of the blood platelets from cord blood of 69 eutrophic
      newborns differed in relation to sex. In female newborns we noted 8.13% killed
      Staphylococcus aureus ATCC 6538 P, whereas in male newborns only 2.92%. These
      data point to the role of platelets in unspecific defense against infections.

PMID- 12051297
TI  - A new technique for three-dimensional measurements of skin surface contours:
      evaluation of skin surface contours according to the ageing process using a
      stereo image optical topometer.
AB  - The evaluation of skin surface contours can be carried out by various techniques,
      including the use of a stylus profilometer, a laserprofilometer and a
      conventional optical profilometer (COP). But these methods have some drawbacks
      because their data are basically obtained from two-dimensional algorithms. So a
      new technique has been developed based on a new concept: a stereo image
      processing technique which is considered in this paper. Since a pair of stereo
      images contains depth information, the 'disparity', or the difference between the
      left and right images, enables the production of three-dimensional coordinates.
      This study was performed to evaluate the change of skin surface contours
      according to the ageing process. The stereo image optical topometer (SOT) is a
      new instrument used for the three-dimensional evaluation of skin surface
      contours. Thus. five new parameters have to be developed, such as mean surface
      roughness (S(a)), mean depth of roughness (S(z)), three-dimensional length
      (S(L)), three-dimensional area (S(A)), and three-dimensional volume (S(V)). S(a),
      S(L) and S(A) have shown a statistically significant increase in the seventies
      age group. S(z) has also shown a significant increase in the twenties and over
      sixties age groups. The coefficient variation of the height of the skin surface
      using a COP varies between 14.76 and 6.57, but that using a SOT is between 2.18
      and 2.69, according to age variation. In conclusion, the SOT system is a more
      reliable and useful method for evaluating skin surface contours than the COP
      system. Among the three-dimensional parameters which were made in this study,
      S(A), S(L) and S(a) seem to be useful as reliable parameters for evaluating skin
      surface contours in the ageing process.

PMID- 12051298
TI  - Evaluation of basic performance and applicability of a newly developed in vivo
      nitric oxide sensor.
AB  - Direct measurement of nitric oxide (NO) is of great importance and value for both
      in vitro and in vivo studies on dynamic NO bioactivity. Here, we evaluated the
      basic performance of a newly developed NO sensor (Innovative Instruments, Inc.).
      Unlike other NO sensors, the new NO sensor has a highly durable, gas-permeable
      coating and is affected much less by electrical interference due to its
      integrated structure where working and reference electrodes are combined in a
      single element. Calibration with NO gas showed high sensitivity of about 580 pA
      per nmol-NO l(-1) (the detection limit 0.08 nmol-NO l(-1), S/N = 3). This sensor
      also showed high selectivity (25,000 times and more) to NO, compared with NO
      related reagents such as L-arginine, N(G)-monomethyl-L-arginine, acetylcholine,
      nitroglycerin (NTG) and tetrahydrobiopterin as well as dissolved oxygen. As an in
      vivo application, the sensor was located in the anaesthetized rat abdominal aorta
      to measure NTG-derived plasma NO. lntra-aortic infusion of 0.5 mg NTG caused a
      measurable increase in plasma NO level (2.0 +/- 2.2 nmol l(-1), mean +/- SD, n =
      3). In conclusion, the new NO sensor demonstrated a satisfying performance for
      both in vitro and in vivo applications.

PMID- 12051299
TI  - A novel ultrasound technique to estimate right ventricular geometry during
      fibrillation.
AB  - Finite element modelling of the heart for the purpose of studying the electric
      fields of defibrillation shocks requires knowledge of the geometry of the heart
      during fibrillation. However, the standard method of measuring this geometry,
      MRI. cannot be used during fibrillation because the heart geometry changes
      rapidly and perhaps unpredictably. We present a new ultrasound approach to
      measuring the right ventricular geometry during fibrillation and preliminary data
      using this technique. In six anaesthetized pigs, we find that a short axis cross
      sectional area of the right ventricle increases by 38% during a 30 s episode of
      ventricular fibrillation. A long axis cross-sectional area increases by 19%
      during this same time. By fitting parameters of a simple geometric model to the
      experimental data, we estimate that the volume of blood in the right ventricular
      cavity increases by approximately 30% during the episode of ventricular
      fibrillation. We present the first study of the RV area during-fibrillation with
      the estimated volume. Our data suggest changes in defibrillation threshold may be
      linked to current shunting through the increased blood volume.

PMID- 12051300
TI  - Airway resistance estimation by best fit analysis in very premature infants.
AB  - Plethysmographic measurement of airway resistance (R(aw)) has been determined by
      single-point analysis, usually at 50% of maximum inspiratory flow (MIF). Computer
      assisted (best fit) analysis, however, allows R(aw) to be calculated by applying
      a regression line to any portion of the plethysmograph pressure-flow loop. We
      determined whether the results of best fit analysis using a computer program,
      sampling at 200 Hz, were influenced by the portion of the inspiratory loop
      analysed and if best fit or single-point analysis gave more reproducible results.
      Twenty infants of median gestational age 26 (range 24-28) weeks, were studied at
      a median age of 12 (12-14) months corrected for prematurity. R(aw) was calculated
      by best fit analysis between 0 and 33% MIF, 0 and 50% MIF and 0 and 67% MIF and
      single-point analysis at 50% of MIF. Similar mean R(aw) values were obtained by
      best fit analysis between 0 and 33% MIF (2.79 kPa/(l/s)) and 0 and 50% MIF (3.01
      kPa/(l/s)) and single-point analysis at 50% MIF (2.86 kPa/(l/s)), but best fit
      analysis between 0 and 67% gave higher results (3.60 kPa/(l/s)), p < 0.0001.
      Within the linear portion of the inspiratory loop, the mean intrasubject
      coefficient of variation was lowest for best fit analysis between 0 and 50% MIF.
      Best fit computerized analysis between 0 and 50% MIF is recommended as the
      analysis of choice.

PMID- 12051301
TI  - In-shoe measurement of plantar blood flow in diabetic subjects: results of a
      preliminary clinical evaluation.
AB  - The findings of clinical pilot study (n = 9 subjects) using a new laser Doppler
      sensor for assessing blood flux in plantar skin tissue are described. Cutaneous
      blood perfusion was recorded under the first metatarsal head (right foot) in
      standing and walking. The sensor was located in a measurement shoe custom made
      for each test subject. The test group comprised diabetic patients (type II) with
      vascular (n = 3) or neuropathic (n = 3) complications and three controls. All
      subjects were Caucasian males and in the age range considered particularly at
      risk of diabetic foot problems (mean 61 years, 51-72 years). Following static
      loading for 2, 3 and 4 min the blood.flux response increased rapidly in the
      control (mean = 10 s) and neuropathic (mean = 18 s) groups to a well-defined,
      peak blood flow. For the vascular group. the blood flux response was typically a
      slower rise (mean = 30 s) to a poorly defined peak blood flow value. Due to
      movement artifact a reliable signal could only be obtained for the swing phase of
      gait during which blood flux was observed to increase linearly. This was
      interpreted as reperfusion of the tissue following unloading. The rates of
      reperfusion expressed in arbitrary units (of blood flux) per millisecond (au ms(
      1)) were 6.1-7.9 au ms(-1) for the control, 4-6.2 au ms- for the vascular and 2.3
      4.5 au ms(-1) for the neuropathic groups. The feasibility of assessing the
      microcirculation of the plantar skin under conditions of static and dynamic
      loading, with the foot in-shoe, has been demonstrated for the first time. The
      results suggest that abnormal responses may be obtained from asymptomatic feet of
      diabetic patients with vascular and/or neuropathic complications. This method of
      assessment could be of use in predicting the occurrence of ulceration in the
      diabetic foot.

PMID- 12051302
TI  - Quantitative evaluation of the relative contribution ratio of cerebral tissue to
      near-infrared signals in the adult human head: a preliminary study.
AB  - Combining spatially- and time-resolved spectroscopies. we attempted to
      quantitatively evaluate the contribution ratio of the partial mean pathlength of
      cerebral tissue to the observed overall mean pathlength, in which haemoglobin
      concentrations were selectively changed by administration of acetazolamide. When
      acetazolamide was administered, the observed increases in oxygenated haemoglobin
      depended on the probe distance, which became progressively larger at distances of
      2, 3 and 4 cm. Increases in oxygen saturation were detected at 3 and 4 cm
      spacing, but not at 2 cm. Assuming that the modified Lambert-Beer's law can exist
      in the inhomogeneous structure of the head, then, we could estimate the
      contribution ratio of the cerebral tissue to optical signals at the probe
      distances of 2, 3 and 4 cm as 33%, 55% and 69%, respectively. Using these values,
      we recalculated acetazolamide-induced concentration changes in oxygenated
      haemoglobin in the cerebral tissue, which resulted in the same values at
      distances of 2, 3 and 4 cm as expected. Thus, our present method opened the door
      to the possibility of selectively obtaining optical signals attributed to
      cerebral tissue.

PMID- 12051303
TI  - Acoustical characterization of bone using a cylindrical model and time of flight
      method: edge reconstruction and ultrasound velocity determination in cortical
      bone and in medullar marrow.
AB  - Our objective is to evaluate the external and internal dimensions of bone
      diaphysis and the speed of sound in cortical bone and in medullar marrow. The
      diaphysis is modelled by a cylindrical hollow tube. The theory of rays is used
      and an approximation allows us to break free from the data gained by ultrasonic
      field amplitude. Then, acoustical and dimensional parameters are only related to
      the time of flight of reflected and transmitted acoustic echoes in the tube. From
      the arrival time of particular echoes, the inverse problem resolution then allows
      us to experimentally determine the sought parameters. This method is validated in
      vitro on a bovine femur and gives satisfactory results.

PMID- 12051304
TI  - A study on the optimum order of autoregressive models for heart rate variability.
AB  - Heart rate variability (HRV) has been used as a non-invasive marker of the
      activity of the autonomic nervous system and its spectrum analysis gives a
      measure of the sympatho-vagal balance. If short segments are used in an attempt
      to improve temporal resolution, autoregressive spectral estimation, where the
      mode] order must be estimated, is preferred. In this paper we compare four
      criteria for the estimation of the 'optimum' model order for an autoregressive
      (AR) process applied to short segments of tachograms used for HRV analysis. The
      criteria used were Akaike's final prediction error, Akaike's information
      criterion, Parzen's criterion of autoregressive transfer function and Rissanen's
      minimum description length method, and they were first applied to tachograms to
      verify (i) the range and distribution of model orders obtained and (ii) if the
      different techniques suggest the same model order for the same frames. The four
      techniques were then tested using a true AR process of known order p = 6; this
      verified the ability of the criteria to estimate the correct order of a true AR
      process and the effect, on the spectrum, of choosing a wrong model order was also
      investigated. It was found that all the four criteria underestimate the true AR
      order; specifying a fixed model order was then looked at and it is recommended
      that an AR order not less than p = 16, should be used for spectral analysis of
      short segments of tachograms.

PMID- 12051305
TI  - Method for ventricular fibrillation detection in the external electrocardiogram
      using nonlinear prediction.
AB  - The automatic external defibrillator is a lifesaving device which processes and
      analyses the electrocardiogram (ECG) and delivers defibrillation shock when
      necessary. The accuracy of the built-in algorithm for ECG analysis must be very
      high, with sensitivity and specificity aimed to approach the maximum values of
      100%. An algorithm based on nonlinear prediction of the external ECG signal is
      proposed. It extracts seven parameters characterizing the prediction possibility
      of the assessed ECG signal. By means of the K-nearest neighbours rule the
      diagnostic accuracy of different combinations of these parameters was evaluated.
      Thus the accuracy obtained was higher than 95% with sensitivity and specificity
      values depending on the combination of parameters. The method was tested with ECG
      records from the widely recognized databases of the American Heart Association
      (AHA) and Massachusetts Institute of Technology (MIT).

PMID- 12051306
TI  - A comparative study of tests of cardiac parasympathetic nervous activity in
      healthy human subjects.
AB  - Conventional tests of cardiac parasympathetic nervous system (PNS) activity were
      compared with the high frequency component of the heart rate power spectrum in a
      heterogenous group of normal subjects encompassing a wide age range. The data
      suggest that the linear associations between the various conventional tests of
      parasympathetic nervous activity even when statistically significant, were
      relatively modest, with r values ranging from 0.23 to 0.53. Three of the five
      conventional tests of parasympathetic nervous activity were significantly
      correlated (r = 0.33 to 0.46) with the absolute high frequency power of RR
      variability. However, these relationships were poorer and non-significant when
      the high frequency power spectrum was normalized for total power (r = 0.06 to
      0.19, NS). An evaluation of the heart rate responses to cough and a single
      maximal hand grip indicated that the responses were repeatable but that the
      extent to which these manoeuvres induced vagally mediated cardioacceleration was
      significantly lesser than the other conventional tests of PNS activity. Taken
      together, the data suggest that despite the advent of heart rate variability
      measures, it is advisable to use multiple tests of parasympathetic nervous
      activity while evaluating autonomic dysfunction, since, despite the specificity
      of the tests, there is a variable correlation between them.

PMID- 12051307
TI  - Effect of changes in heart rate and in action potential duration on the
      electrocardiogram T wave shape.
AB  - The mechanisms responsible for changes in T wave symmetry and amplitude with
      changes in heart rate and action potential duration were investigated. A computer
      model of normal left ventricular repolarization was used to simulate the T waves
      on the surface 12-lead ECG. The effect of heart rate changes was studied by
      varying the ratio between dispersion of repolarization (Disp) and action
      potential repolarization duration (APRD). With constant dispersion. as heart rate
      increases, APRD decreases and the ratio Disp/APRD increases. T waves were
      simulated while varying the Disp/APRD ratio from 3.6% to 100%. The T wave
      symmetry ratio measured from the areas either side of the peak (SRarea), the
      symmetry ratio from the times either side of the peak (SRtime) and the T wave
      amplitude (Tamplitude) were calculated from each simulated ECG. SRarea decreased
      from 1.42 to 0.77, SRtime from 1.75 to 1.04 and the Tamplitude increased from 0.
      19 mV to 2.30 mV. The stability of results with variation in model
      characteristics was also investigated, by moving the heart +/- 20 mm on all three
      axes, rotating the heart axes by +/- 10 and by modifying all constants defining
      the action potential by +/- 5% and +/- 10%. T wave amplitude was sensitive to
      changes in heart position, as the heart was moved towards the body surface.
      However, T wave shape changed very little with heart position or rotation, with
      the SD of SRarea varying by less than 0.05 over an SRarea range of 0.65 for
      different values of Disp/APRD ratio. We have shown from our model that cardiac T
      waves increase in amplitude, and become more symmetric with their peaks becoming
      central as APRD shortens with increasing heart rate, agreeing with clinical
      observations. These results help to explain the T wave shape changes which occur
      when heart rate increases.

PMID- 12051308
TI  - Microvascular blood flow and skin temperature changes in the fingers following a
      deep nspiratory gasp.
AB  - The aims of this study were to quantify the changes in finger pulp skin
      temperature, laser Doppler flow (LDF, microvascular flux) and photoplethysmogram
      (PPG, microvascular blood volume pulsatility), induced by a deep inspiration in
      healthy subjects, and to investigate the repeatability of these responses within
      a measurement session and between measurement sessions on separate days. A system
      comprising an electronic thermometer, a laser Doppler flowmeter and a PPG
      amplifier measured simultaneous vasoconstrictor responses to a deep inspiratory
      gasp from three adjacent fingers of one hand. Clearly defined responses were
      obtained in 15 of the 17 subjects studied. Skin temperature fell in all of these
      subjects after each gasp, with a median fall of 0.089 degrees C (P < 0.001). The
      median value of LDF flux reduction was 93% (P < 0.001) indicating a momentary
      almost complete shut-down of microvascular blood flow; and PPG also showed a
      large response relative to pulse amplitude of 2.6 (P < 0.001). The median times
      for waveforms to reach their minimum were 4.6 s (PPG), 6.3 s (LDF) and 29.1 s
      (skin pulp temperature), with median delays between minima of LDF and PPG of 1.6
      s (P < 0.001) and skin temperature and PPG of 23.5 s (P < 0.001). The vascular
      responses of skin temperature, LDF and PPG to an inspiratory gasp were
      repeatable, with temperature change repeatable to within 10% of the median
      subject change.

PMID- 12051309
TI  - Measuring caffeine-induced changes in middle cerebral artery blood velocity using
      transcranial Doppler in patients recovering from ischaemic stroke.
AB  - Acute ingestion of caffeine is known to reduce cerebral blood flow in normal
      volunteers and in certain patient groups. There is no evidence that this causes
      problems in the normal population. However, there may be implications if a
      similar reduction occurs in patients recovering from an ischaemic stroke, in whom
      local blood flow has already been reduced. Transcranial Doppler provides a non
      invasive method for measuring changes in middle cerebral artery (mca) blood
      velocity. A method for obtaining consistent. reliable measurements was developed
      and used in a double blind, randomized, crossover study on 20 patients (18 M, 2
      F; mean age 70) recovering from ischaemic stroke in the mca territory. Middle
      cerebral artery blood velocity was measured bilaterally using transcranial
      Doppler before and after 250 mg caffeine (equivalent to about two cups of filter
      coffee) or matched placebo. Caffeine caused an average 12% reduction in blood
      velocity compared to placebo in the hemisphere affected by the stroke (95%c CI 8%
      16%, p < 0.00001), and a 12% reduction in the non-affected hemisphere (95% CI 6%
      18%, p < 0.001). The clinical implications are unclear at present, and imaging
      techniques will be required to establish whether caffeine does reduce flow to
      hypo-perfused regions.

PMID- 12051310
TI  - Relationship between detrended fluctuation analysis and spectral analysis of
      heart-rate variability.
AB  - The recently-introduced technique of detrended fluctuation analysis (DFA) for
      heart-rate variability appears to yield improved prognostic power in
      cardiovascular disease through calculation of the fractal scaling exponent alpha.
      However, the physiological meaning of alpha remains unclear. In DFA, the signal
      is segmented into lengths from 4 to 64 beats. For each segmentation length (n),
      the individual segments are cumulated, detrended and the sum of the squares (F2)
      of residuals calculated. Alpha is the slope of log(F) against log(n). We show
      mathematical equivalence between alpha calculated by DFA and by a novel
      alternative method using frequency-weighted power spectra. We show F2 (and thus
      alpha) can be obtained from a frequency-weighted power spectrum without DFA. To
      do this, we cumulate and detrend the Taylor series of individual Fourier
      components. F2 is found to depend on the relationship between the signal period
      and segment length. F2 can therefore be expressed in terms of frequency-weighted
      power spectra. From this, the alpha coefficient of DFA can then be described in
      power-spectral terms, which facilitates exploration of its physiological basis.
      We confirm these findings using samples from 20 healthy volunteers and 40
      patients with heart failure.

PMID- 12051311
TI  - In vivo PIV measurement of red blood cell velocity field in microvessels
      considering mesentery motion.
AB  - As endothelial cells are subject to flow shear stress, it is important to
      determine the detailed velocity distribution in microvessels in the study of
      mechanical interactions between blood and endothelium. Recently, particle image
      velocimetry (PIV) has been proposed as a quantitative method of measuring
      velocity fields instantaneously in experimental fluid mechanics. The authors have
      developed a highly accurate PIV technique with improved dynamic range. spatial
      resolution and measurement accuracy. In this paper, the proposed method was
      applied to images of the arteriole in the rat mesentery using an intravital
      microscope and high-speed digital video system. Taking the mesentery motion into
      account, the PIV technique was improved to measure red blood cell (RBC) velocity.
      Velocity distributions with spatial resolutions of 0.8 x 0.8 microm were obtained
      even near the wall in the centre plane of the arteriole. The arteriole velocity
      profile was blunt in the centre region of the vessel cross-section and sharp in
      the near-wall region. Typical flow features for non-Newtonian fluid were shown.
      Time-averaged velocity profiles in six cross sections with different diameters
      were compared.

PMID- 12051312
TI  - Nonlinear dynamics of the left ventricle.
AB  - The cnoidal method is applied to solve the set of nonlinear dynamic equations of
      the left ventricle. By using the theta-function representation of the solutions
      and a genetic algorithm, the ventricular motion can be described as a linear
      superposition of cnoidal pulses and additional terms, which include nonlinear
      interactions among them.

PMID- 12051313
TI  - Instrumentation to evaluate neural signal recording properties of micromachined
      microelectrodes inserted in invertebrate nerve.
AB  - The design and characterization of instrumentation for application in evaluating
      the neural signal recording properties of probe-type microelectrodes,
      micromachined from silicon, are reported. Key aspects include the close matching
      of gain and frequency response between channels (better than 1%), flexibility in
      signal conditioning options, the ability to operate with a wide range of
      (microelectrode) recording site dimensions (4 microm x 4 micrm to 50 microm x 50
      microm), and hence impedances, and the facility to monitor and store
      instrumentation settings on computer along with the recorded signals. Noise
      levels ranged from 3.7 microV rms for a 50 microm site, to 11.7 microV rms for a
      microm site, measured in saline. Close matching between channels was required to
      enable comparisons between different sites and different probes to be made with
      confidence; however, the instrumentation could be readily applied to less
      demanding applications.

PMID- 12051314
TI  - 'Slide whistle' breath sounds: acoustical correlates of variable tracheal
      obstruction.
AB  - We report a case of a man who developed severe shortness of breath and the
      finding of breath sounds that rose in frequency during inspiration and fell
      during expiration. These unusual sounds were caused by a spherical tumour arising
      from the main carina that nearly completely obstructed the distal trachea. The
      frequency variation disappeared after the removal of the mass. We evaluated this
      phenomenon using a modelling technique that we had previously developed to
      analyse the human airways as acoustical tubes. This analysis revealed that the
      acoustical conditions in the trachea were substantially modified by the presence
      of the solid mass as the trachea slightly dilated during inspiration, partially
      relieving the obstruction. Most of the anomalous characteristics of the breath
      sounds could be explained using this model. We conclude that a detailed
      understanding of the acoustic conditions of the airways allows correlation with
      anatomical and physiological conditions and may be of use in diagnosis or
      evaluation of the airways in health and disease.

PMID- 12051315
TI  - Comparing spot electrode arrangements for electric impedance cardiography.
AB  - This study investigates whether an arrangement with nine spot electrodes, for
      thoracic bio-impedance cardiography, can be replaced by an arrangement with five
      spot electrodes. The study was conducted on 15 healthy subjects, six females and
      nine males, in supine rest. The variables obtained from the measurements were the
      mean of the impedance of the thorax segment between the recording electrodes, the
      maximum negative deflection of the first derivative of the thoracic impedance,
      the left ventricular ejection time and an estimate of left ventricular stroke
      volume. An analysis of variance for a randomized complete block design was used
      to determine whether significant differences exist in the group means of the
      observed variables between six different electrode arrangements. If no
      statistically significant differences were found in these group means between
      pairs of arrangements, Bland and Altman analyses were used to determine the
      differences in the observed variables between pairs of arrangements for
      individual subjects. This study concludes that reducing the number of spot
      electrodes from nine to five, does not yield significant differences in the group
      means of the observed variables, but it could result in large differences in the
      values of these variables for individual subjects.

PMID- 12051316
TI  - Improvement of multi-channel isolated bio-potential amplifiers using
      multiplexing.
AB  - We propose a simple isolated link circuit for a multi-channel bio-potential
      amplifier, by adapting the multiplexing/demultiplexing technique that is
      generally used in digital circuit design. The reduced number of isolation
      amplifiers, due to the multiplexing technique, results in an increase in the
      amount of isolation, as well as a reduction in manufacturing cost. The simple
      incorporation of a dead-zone in multiplexed timing, and a pull-down resistor in
      the multiplexed signal line, enables a multiple isolated bio-signal transmission
      over the shared isolation amplifier, with an affordable inter-channel cross talk.

PMID- 12051317
TI  - Key to better qualitative diagnostic calibrations in respiratory inductive
      plethysmography.
AB  - Least-squares estimates for coefficients of linear models that predict tidal
      volume (VT) via respiratory inductive plethysmography (RIP) are given. The
      qualitative diagnostic calibration sum formula M(RC + KAbd) arises for idealized
      thoracoabdominal co-ordination within this model-fitting framework. For a normal
      synchronous breath K is then optimally determined from the ratio of its
      associated ribcage (RC) and abdomen (Abd) movement standard deviations, not from
      a ratio that applied to a previously measured breath. M merely rescales relative
      changes in (RC + KAbd) to absolute changes in VT for correct proportioning. RC
      and Abd move in complete antipathy during an obstructive apnoea, so use of
      optimal K ensures (RC + KAbd) tends to zero for such unproductive breathing
      efforts. The interpretation is extended to more general breathing patterns by
      using a complementary difference expression M(RC-KAbd) to help identify any
      antagonistic respiratory actions. The two new constructs are equivalent to the
      principal components of the combined ribcage and abdomen movements. Together they
      demonstrate versatile capability in uncalibrated RIP applications for obstructive
      apnoea detection and tracking relative changes in VT during paradoxical or
      variable natural breathing. Calibration is appropriate for model-fitting quality
      assessment but otherwise usually too patient demanding, unnecessary or
      detrimental to prediction monitoring efficacy.

PMID- 12051318
TI  - Sleep studies for sleep apnoea.
AB  - Sleep studies have grown to encompass a broad range of technologies employed to
      study and diagnose a variety of sleep disorders. From their inception in
      neurophysiology laboratories interested in investigating primary disorders of
      sleep architecture from psychiatric illness, their remit has widened such that
      their most common role is currently to diagnose secondary sleep disruption from
      respiratory, cardiovascular or other systemic causes. This review outlines the
      pathophysiology of obstructive sleep apnoea in particular and how sleep studies
      have improved our understanding of the complex dynamic changes in blood gas
      tensions, cardiovascular control and cerebral arousal that occur with these
      repetitive events. We review the historical development of standard laboratory
      based sleep studies and discuss their limitations in staging sleep, reflecting
      the episodes of increased upper airway resistance that underlie these disorders
      and their ability to predict individuals' symptoms or response to medical or
      surgical therapies. We then describe some alternative signals that have been
      employed to monitor the physiological changes in upper airway resistance and
      arousal with a discussion of some of the evidence that these 'limited' studies
      may provide diagnostic information that can guide clinical decision making and
      may predict the outcome without the need, in some cases, for more complex and
      costly laboratory-based studies.

PMID- 12051319
TI  - How can we measure substrate, metabolite and neurotransmitter concentrations in
      the human brain?
AB  - Cerebral injury and disease is associated with fundamental derangements in
      metabolism, with changes in the concentration of important substrates (e.g.
      glucose), metabolites (e.g. lactate) and neurotransmitters (e.g. glutamate and y
      aminobutyric acid) in addition to changes in oxygen utilization. The ability to
      measure these substances in the human brain is increasing our understanding of
      the pathophysiology of trauma, stroke, epilepsy and tumours. There are several
      techniques in clinical practice already in use and new methods are under
      evaluation. Such techniques include the use of cerebral probes (e.g.
      microdialysis. voltammetry and spectrophotometry) and functional imaging (e.g.
      positron emission tomography and magnetic resonance spectroscopy). This review
      describes these techniques in terms of their principles and clinical
      applications.

PMID- 12051320
TI  - President's editorial--the changing practice of forensic science.

PMID- 12051321
TI  - Trace DNA: a review, discussion of theory, and application of the transfer of
      trace quantities of DNA through skin contact.
AB  - Advances in STR PCR DNA profiling technology allow for the analysis of minute
      quantities of DNA. It is frequently possible to obtain successful DNA results
      from cellular material transferred from the skin of an individual who has simply
      touched an object. Handling objects, such as weapons or other items associated
      with a crime, touching surfaces, or wearing clothing, may represent sufficient
      contact to transfer small numbers of DNA bearing cells, or trace DNA, which can
      be successfully analyzed. With this minimal amount of contact required to yield a
      suspect profile comes tremendous crime solving potential, and a number of
      considerations for prudent application, and the maximization of evidentiary
      value. Evidentiary materials not previously considered must be recognized and
      preserved, and the resulting DNA type profiles interpreted in their proper
      forensic context.

PMID- 12051322
TI  - Criminal responsibility and cannabis use: psychiatric review and proposed
      guidelines.
AB  - An evaluation of the criminal responsibility of an offender who has consumed
      cannabis necessitates knowledge of the effect of the product on the offender's
      mental state at the time of the alleged offense. However, the effects induced by
      cannabis are numerous and the forensic psychiatrist should base his diagnosis and
      his evaluation on facts which are as objective as possible. A selective
      literature review, using the computerized databases Medline, Psychlit and Embase,
      has been carried out to aid evaluation from a forensic psychiatry point of view.
      Biological means of cannabis detection, and the difficulties associated with
      using them to understand the clinical effect that the product has on any one
      user, are shown. Eight major categories which can be used in the domain of
      forensic psychiatry are detailed in this review: Acute usual effects, acute
      adverse effects, mood disturbance, acute toxic confusion, acute psychotic
      reaction, chronic paranoid psychosis, amotivational syndrome or other long term
      effects, and flashbacks. For each of these categories the effects of cannabis
      intoxication on cognitive and volitional capacities are analyzed, and guidelines
      for the evaluation of criminal responsibility are proposed.

PMID- 12051323
TI  - In vivo facial tissue depth measurements for white British children.
AB  - This paper reports the results of a study of facial tissue depth measurement in
      White British children of both sexes, aged between 11 and 18 years. The purpose
      of this research was to increase the information available upon tissue depth data
      for children, primarily for use in forensic facial reconstruction. Facial tissue
      depths were measured at 21 anatomical points using ultrasonic echo-location. The
      mid-philtral, upper lip border and lower lip border points showed consistently
      larger tissue depths in the males than the females, and the zygomatic attachment
      showed consistently larger tissue depths in the females than the males. The males
      showed a general increase in tissue depth with an increase in age at all the mid
      line facial points and the cheek points. The females showed increased tissue
      depth with age at all the points except the infra-orbital, lateral orbital, mid
      zygomatic arch and mid-mandibular points. A table of mean tissue depths was
      developed for males and females divided into two-yearly age groups.

PMID- 12051324
TI  - Experiments in the combustibility of the human body.
AB  - This paper provides possible explanations for two previously misunderstood
      circumstances surrounding cases of so-called "spontaneous human combustion"--the
      nearly complete cremation of human bone, and the failure of such fires to spread
      to nearby combustibles. Two experiments were conducted. The first involved the
      cremation of "healthy" and "osteoporotic" human bone and observing the resulting
      fragmentation and color change. Osteoporotic elements consistently displayed more
      discoloration and a greater degree of fragmentation than healthy ones. The second
      experiment involved the combustion of a sample of human tissue and observation of
      the flame height and burning area in order to calculate the effective heat of
      combustion. The resulting heat was 17kJ/g indicating a fire that is unlikely to
      spread. These results, which are among the first obtained for human samples, lend
      further support and credence to previous scientific explanations for "spontaneous
      human combustion."

PMID- 12051325
TI  - Forensic analysis of ignitable liquids in fire debris by comprehensive two
      dimensional gas chromatography.
AB  - The application of comprehensive two-dimensional gas chromatography (GC x GC) for
      the forensic analysis of ignitable liquids in fire debris is reported. GC x GC is
      a high resolution, multidimensional gas chromatographic method in which each
      component of a complex mixture is subjected to two independent chromatographic
      separations. The high resolving power of GC x GC can separate hundreds of
      chemical components from a complex fire debris extract. The GC x GC chromatogram
      is a multicolor plot of two-dimensional retention time and detector signal
      intensity that is well suited for rapid identification and fingerprinting of
      ignitable liquids. GC x GC chromatograms were used to identify and classify
      ignitable liquids, detect minor differences between similar ignitable liquids,
      track the chemical changes associated with weathering, characterize the chemical
      composition of fire debris pyrolysates, and detect weathered ignitable liquids
      against a background of fire debris pyrolysates.

PMID- 12051326
TI  - Handguns and ammunitions indicators extracted from the GSR analysis.
AB  - The computer automated scanning electron microscope. X-ray microanalysis of
      Firearms Discharge Residue (FDR) can reveal substantial information about the
      circumstances of their generation beyond the presence of characteristic gunshot
      residue (GSR). Indicators of the type of weapon and ammunition used can he
      obtained from the distribution of GSR particle shapes and from the multi-element
      analysis of the FDR sample. This is demonstrated for a large database of GSR
      samples from nine different handguns and over 60 different ammunitions. An
      example classification scheme is presented for the supporting particles generally
      found present in FDR. When particle type area concentration ratios are normalized
      to the iron (Fe) particle type, results show it is possible to distinguish much
      about the metal used in the weapon manufacture, whether it was of large or small
      caliber, whether the bullets were jacketed or plated, and whether the cartridge
      cases were of aluminum, brass, or nickel-plated brass. Standardization of such
      analytical schemes would be advantageous.

PMID- 12051327
TI  - Brake linings: a source of non-GSR particles containing lead, barium, and
      antimony.
AB  - The observation of environmental particles similar in composition to gunshot
      residue (GSR) are not new to forensic experts and have been described in the
      scientific literature. In order to better define the origin of these particles,
      brake linings and their wear products were examined by SEM-EDX. The results
      obtained demonstrate that some types of brake linings contain lead, barium, and
      antimony and that they can represent a source of particles showing GSR-like
      elemental profiles. Most of these particles can be easily discriminated from
      primer discharge residue because of the high levels of iron or the presence of
      "prohibited" elements in the spectrum. However, particles with iron at minor or
      trace levels and lacking "prohibited" elements were also found. It is thus
      advisable to use caution when describing the composition of similar particles as
      "unique" to primer discharge residue. The strict application of a rigorous
      morphological criterion is also recommended.

PMID- 12051328
TI  - Interpretation of glass composition measurements: the effects of match criteria
      on discrimination capability.
AB  - The concentrations of ten elements in 209 unrelated glass specimens received as
      evidence were used to assess the frequencies of errors of false association (Type
      II errors) using several comparison criteria at specified significance levels
      (Type I errors). Pairwise comparisons of the samples using either the equal
      variance t-test or Welch's modification (unequal variances) result in a small
      number of errors of false association, even when adjusting the significance level
      (Bonferroni correction) for multivariate comparisons. At the 95% confidence level
      (overall Type I error of 0.05, or individual element comparison error of 0.005),
      only two Type II errors are made in 21736 comparisons (0.009%) when using the
      equal-variance t-test for comparison of sample means. In this study, the range
      overlap test using three replicate measurements per specimen results in no errors
      of false association. Most specimen pairs in this data set are readily
      discriminated either by differences in the concentrations of several elements or
      by an extremely large difference in the concentrations of one or more element.

PMID- 12051329
TI  - Online Y-chromosomal short tandem repeat haplotype reference database (YHRD) for
      U.S. populations.
AB  - We describe here an online Y-chromosomal short tandem repeat haplotype reference
      database (YHRD) for U.S. populations, which represents 9-locus Y-STR haplotypes
      for 1705 African-Americans, European-Americans and Hispanics as of October 2001.
      This database is available online (http://www.ystr. org/usa/), free to access and
      was generated in order to supply the U.S. forensic DNA community with a valuable
      resource for frequencies of complete or incomplete 9-locus Y-STR haplotypes, as
      well as information about typing protocols and population genetic analyses.
      Pairwise R(ST)-statistics derived from the Y-STR haplotypes indicate no
      significant substructure among African-American populations from different
      regions of the U.S., nor (usually) among European-American and Hispanic
      populations. Thus, pooling of Y-STR haplotype data from regional populations
      within these three major groups is appropriate in order to obtain larger sample
      sizes. However, pooling of different major populations is generally not
      recommended due to statistically significant differences between African-American
      populations and all European-American/Hispanic populations, as well as between
      some European-American and Hispanic populations.

PMID- 12051330
TI  - Interpreting small quantities of DNA: the hierarchy of propositions and the use
      of Bayesian networks.
AB  - The dramatic increase in the sensitivity of DNA profiling systems that has
      occurred over recent years has led to the need to address a wider range of
      interpretational problems in forensic science. The issues surrounding questions
      of the kind "whose DNA is this?" have been the subject of considerable
      controversy but now it is clear that the emphasis is shifting to questions of the
      kind "how did this DNA get here?" Such issues are discussed in this paper and new
      insights are provided by two particular recent developments. First, the notion of
      the "hierarchy of propositions" that has arisen from a project called Case
      Assessment and Interpretation (CAI) that has been running in the British Forensic
      Science Service (FSS). Second, a technique for drawing inferences in the face of
      many interacting considerations, known as "Bayesian networks"--or "Bayes' nets"
      for short--that has been the subject of an earlier paper in this journal (1). The
      discussion is carried out by means of case studies, based on actual cases. It is
      clear that, whereas the inference in relation to the source of the DNA in a crime
      sample might be overwhelmingly strong, the inference in relation to the
      propositions that a jury must consider relating to the identity of the actual
      offender may be much more tentative.

PMID- 12051331
TI  - The accuracy and precision of third molar development as an indicator of
      chronological age in Hispanics.
AB  - The accuracy and precision of chronological age estimation based on the stages of
      third molar tooth development was studied in a sample of 679 radiographs from
      individuals of Hispanic origin. The age range was 14.0 to 25.0 years. Eight
      raters from the University of Texas Health Science Center at Houston Dental
      Branch evaluated the radiographs according to Demirjian's schematic definitions
      of crown and root formation. The objective of this study was to evaluate the
      chronology of third molar development in Hispanics following the protocol of a
      previous study. Within the Hispanic population, the rate of male third molar
      development is greater than that of female third molar development for ten stages
      of crown-root formation. Also within this Hispanic population sample, the rate of
      maxillary third molar development is ahead of mandibular third molar development.
      The mean absolute difference between chronological age and estimated age was +/
      3.0 years in females and +/- 2.6 years in males.

PMID- 12051332
TI  - WinID2 versus CAPMI4: two computer-assisted dental identification systems.
AB  - Disasters produce victims that require identification. Comparing antemortem and
      postmortem dental records provides an important means of identification.
      Computers have assisted this process. Currently, the principal computer programs
      are CAPMI4 and WinID2. The present study compared these programs on a sample of
      100 simulated victims and 105 simulated postmortem fragments. CAPMI4 provided 48
      correct matches and WinID2 provided 71 correct matches. In addition, comparisons
      were made within WinID2 to determine which of its three dental data sets was the
      most successful for suggesting correct matches.

PMID- 12051333
TI  - The emotional and psychological impact of mass casualty incidents on forensic
      odontologists.
AB  - Motivated by the findings of a previous research project, 38 forensic
      odontologists with known occupational experience of mass casualty incidents
      completed a questionnaire designed to elicit both quantitative and qualitative
      data. The questionnaire sought to provide an insight into the psychological and
      emotional impact of conducting work of this nature. Two psychometric scales were
      included in the questionnaire, The Positive and Negative Affect scale (PANAS) and
      the Impact of Events Scale (IOE). In addition, a number of open-ended questions
      relating to the personal experiences of the respondent during the mass casualty
      incident were also included. Quantitative findings indicate that on the whole
      mass casualty incidents resulted in a positive experience for the respondents,
      although over a third reported being distressed, upset or irritable at some time
      during the event. Sense of achievement and camaraderie were among the qualitative
      themes elicited that help explain the positive reactions. Working conditions,
      politics and the ictims were cited as sources of negativity.

PMID- 12051335
TI  - Sharp injury fatalities in New York City.
AB  - We reviewed the case records of all fatalities due to sharp injuries in New York
      City in 1999. The epidemiological profile, circumstances, toxicology results,
      location, and injuries were examined. There were 120 deaths: 101 homicides, 17
      suicides, and 2 accidents. The causes of death included: 112 due to stab(s) with
      or without incised wounds and 8 pure incised wound fatalities of which 5 were
      suicides. The detection of ethanol and/or illicit drugs was 61% in the homicide
      and 12% in the suicide groups. "Defense wounds" were reported in 49% of the
      homicides and "hesitation" wounds were found in 65% of the suicides. There were
      no self-inflicted sharp injuries of the face. Deaths due to a single stab wound
      occurred in 34% (34/101) of the homicides and 24% (4/17) of the suicides. Of
      these 38 deaths, 58% were of the anterior thorax (chest) and 71% injured the
      heart and/or great vessels. The remaining deaths with single stab wounds involved
      the femoral artery, abdominal organs, or head. There were no sharp injury
      suicides by Hispanics, Asians, or anyone under the age of 18 years. Over half of
      the suicides at home occurred in the bathroom and 78% of these occurred in the
      bathtub. Suicide notes were found in 24% of suicides, and an additional 24%
      verbally expressed a plan to commit suicide.

PMID- 12051334
TI  - Decomposition chemistry of human remains: a new methodology for determining the
      postmortem interval.
AB  - This study was conducted to characterize the chemistry associated with the
      decomposition of human remains with the objective of identifying time-dependent
      biomarkers of decomposition. The purpose of this work was to develop an accurate
      and precise method for measuring the postmortem interval (PMI) of human remains.
      Eighteen subjects were placed within a decay research facility throughout a four
      year time period and allowed to decompose naturally. Field autopsies were
      performed and tissue samples were regularly collected until the tissues
      decomposed to the point where they were no longer recognizable (encompassing a
      cumulative degree hour (CDH) range of approximately 1000 (approximately 3
      weeks)). Analysis of the biomarkers (amino acids, neurotransmitters, and
      decompositional by-products) in various organs (liver, kidney, heart, brain,
      muscle) revealed distinct patterns useful for determining the PMI when based on
      CDHs. Proper use of the methods described herein allow for PMIs so accurate that
      the estimate is limited by the ability to obtain correct temperature data at a
      crime scene rather than sample variability.

PMID- 12051336
TI  - Characteristics of assaultive patients with schizophrenia versus personality
      disorder: six year analysis of the Assaulted Staff Action Program (ASAP).
AB  - Literature reviews of individual assaultive patients, repetitively violent
      patients, and restrained assaultive patients document that persons diagnosed with
      schizophrenia or personality disorder are at the highest risk to become
      assaultive. While there has been some initial research of possible predictor
      variables across diagnostic groups, this six-year retrospective study is the
      first to compare only persons with schizophrenia or personality disorder on basic
      demographic and the selected clinical variables of history of violence, personal
      victimization, and substance use disorder. In this study, the variance suggested
      that persons with schizophrenia and personality disorder were both likely to be
      assaultive. Assaults by persons with schizophrenia were somewhat proportional to
      their presence in the population studied. However, personality disordered
      patients represented a disproportional increase from the population studied.
      Younger females with a diagnosis of personality disorder and with histories of
      violence toward others and personal victimization appeared at increased risk to
      be assaultive and to require restraints. The findings and their implications for
      safety and clinical care are discussed.

PMID- 12051337
TI  - Prevalence of drug use in commercial tractor-trailer drivers.
AB  - An enforcement emphasis project, "Operation Trucker Check," was established in
      order to determine the extent to which commercial tractor-trailer drivers were
      operating their vehicles while impaired by drugs. A total of 1079 drivers and
      their vehicles were assessed for driver and equipment violations, and drivers
      additionally underwent preliminary field sobriety tests conducted by drug
      recognition expert (DRE) officers. Anonymous urine specimens for drug analysis
      were requested, and 822 urine specimens were obtained in total. Compliance with
      the drug-testing portion was voluntary, and there was a 19% refusal rate.
      Overall, 21% of the urine specimens tested positive for either illicit,
      prescription, and/or over-the-counter drugs, and 7% tested positive for more than
      one drug. Excluding caffeine and nicotine, the largest number of positive
      findings (9.5%) were for CNS stimulants, such as methamphetamine, amphetamine,
      phentermine, ephedrine/pseudoephedrine, and cocaine. The second most frequently
      encountered drug class were the cannabinoids, with 4.3% of drivers testing
      positive for marijuana metabolites. Only 11 drivers (1.3%) were positive for
      alcohol. Sixteen truck drivers (1.6%) were charged with driving under the
      influence of drugs after a full DRE evaluation was conducted. The results
      indicate that in spite of comprehensive drug testing in the trucking industry,
      some tractor-trailer drivers are continuing to take illicit and other drugs with
      the potential of having a negative effect on their driving ability. On the other
      hand, only a few drivers were, in fact, deemed to be under the influence of drugs
      at the time of driving when evaluated by DRE officers.

PMID- 12051338
TI  - Identification of human urine stains by HPLC analysis of 17-ketosteroid
      conjugates.
AB  - A new method for identifying human urine stains utilizing high-performance liquid
      chromatographic (HPLC) analysis of five major 17-ketosteroid conjugates:
      dehydroepiandrosterone sulfate, etiocholanolone sulfate, etiocholanolone
      glucuronide, androsterone sulfate, and androsterone glucuronide was examined.
      Samples of urine stains were extracted with borate buffer solution (pH 9.3) and
      the extracts were applied onto a Sep-Pak tC18 cartridge. The analytes were eluted
      from the cartridge with methanol. The eluates were prelabeled with 2,4
      dinitrophenylhydrazine in trichloroacetic acid-benzene solution and were
      separated by HPLC on a reversed-phase ODS column using a mobile phase of 80%
      methanol in a buffer consisting of 25 mM sodium acetate in 2% acetic acid. The
      eluates were monitored by a spectrophotometer at 380 nm. While all five 17
      ketosteroid conjugates were clearly detected in the human urine stain samples,
      traces of only some of these conjugates were detected in the animal samples.
      Therefore, the presence of all five 17-ketosteroid conjugates indicated human
      specificity. In addition to the above finding, the properties of those five 17
      ketosteroid conjugates were confirmed by electrospray ionization liquid
      chromatography-mass spectrometry (ESI-LC-MS).

PMID- 12051339
TI  - The identification of sodium fluoroacetate (compound 1080) employing NMR
      spectroscopy.
AB  - Nuclear magnetic resonance (NMR) spectroscopy was employed for the purpose of
      identifying samples of materials suspected of containing sodium fluoroacetate
      (Compound 1080). Acquisition of routine proton (1H) and carbon (13C) NMR spectra
      provided a straight-forward means for determining the presence of Compound 1080
      in the samples and thus afforded a simple method for analysis and identification
      of this compound.

PMID- 12051340
TI  - A 3-D transformation to improve the legibility of license plate numbers.
AB  - In this paper, a novel three-dimensional transformation method for vehicle
      license plate number recognition is proposed. This method provides an efficient
      solution to normalize skew distorted vehicle license plate images. The Hough
      transform is used to estimate the license plate position and the normalization
      angle. After the three-dimensional transformation and normalization processes,
      the vehicle license plate numbers are recognized easily. Real vehicle license
      plate images are used to show the capability of the proposed method. The provided
      method is also useful for other skewed writings, such as the text printed on a
      suspect's shirt.

PMID- 12051341
TI  - The effect of 1,2-indanedione, a latent fingerprint reagent on subsequent DNA
      profiling.
AB  - The compound 1,2-indanedione was recently introduced in our laboratory as an
      operational reagent for developing latent fingerprints on porous surfaces. As
      part of the reagent implementation, a study was carried out in order to determine
      whether either of the two operational 1,2-indanediones formulations interferes
      with further DNA profiling. Both formulations are based on HFE7100 solvent. One
      is acidic and the other neutral. In a controlled experiment, known donors
      attached stamps to envelopes by licking them. The stamped envelopes were
      initially treated with either one indanedione formulation or the other, and DNA
      was then extracted for STR typing. No differences were observed between the STR
      profiles obtained from treated and untreated stamps and envelopes, indicating
      that 1,2-indanedione does not adversely affect the extraction and subsequent
      amplification of the STRs examined. However, preliminary results indicate that
      potential DNA analysis depends on the time interval between the indanedione
      treatment and DNA extraction as no DNA can be recovered six days following
      treatment. For this reason, it is strongly recommended to extract DNA from
      treated items of evidence as soon as possible after indanedione treatment.

PMID- 12051342
TI  - A more sensitive method for the quantitation of genomic DNA by Alu amplification.
AB  - Current procedures for human DNA quantitation reach their limit at 150 pg DNA,
      which is above the limit of the PCR profiling range using Profiler-Plus (Applied
      Biosystems, CA). This study tested the potential for the use of primate specific
      Alu sequences in forensic science for the sensitive detection and quantitaion of
      DNA. A fluorescently labelled primer pair was designed enabling high efficiency
      amplification of the core Alu sequence within primate DNA. Quantitation was
      performed by measurement of fluorescence intensity and comparison to a series of
      standard template DNA amounts via the construction of a standard curve. The new
      Alu-based quantitation protocol developed has shown its feasibility in more
      sensitively quantitating (100-2.5 pg) unknown amounts of human DNA for forensic
      use. The method is compatible with the use and throughput of current forensic
      procedures.

PMID- 12051343
TI  - Melting curve SNP (McSNP) genotyping: a useful approach for diallelic genotyping
      in forensic science.
AB  - The increasing availability of Single Nucleotide Polymorphisms (SNPs) and
      Deletion/Insertion Polymorphisms (DIPs), as well as the outstanding progress in
      SNP genotyping technologies, will impact forensics profoundly. We have developed
      a new method for genotyping SNPs and DIPs, which is based on the determination of
      melting curve profiles of amplified DNA in solution. We have termed this method
      Melting curve SNP (McSNP) genotyping. Melting curve profiles are composites of
      the particular melting temperatures (Tm) of the individual fragments that
      comprise the DNA sample. Simple mixtures of DNA can be resolved in a very robust
      and efficient fashion, since the samples can be scored in the plates in which
      they were amplified with no or very few post-PCR manipulations. As such, McSNP is
      one of the least expensive genotyping methods available and can and should be
      useful in forensic science.

PMID- 12051344
TI  - Use of a Y chromosome probe as an aid in the forensic proof of sexual assault.
AB  - Currently, the most common procedures for the forensic identification of semen
      that may be present due to a sexual assault include the microscopic
      identification of spermatozoa, acid phosphatase activity, or the detection of
      PSA. However, not all cases of sexual assault result in the deposit of semen.
      Fluorescent In Situ Hybridization (FISH) has been found to be a very sensitive
      and specific method for detection of the Y chromosome from male cells. This study
      was undertaken to demonstrate the presence of epithelial cells of male origin in
      the postcoital vaginal tract using a commercially available probe. Results
      identified Y chromosome in intact epithelial cells on postcoital Days 1 through
      4, and on Day 7. Additionally, Y chromosome positive epithelial cells were
      identified in vaginal swabs obtained following intercourse with no ejaculation.
      The method developed in this study demonstrates that FISH is a sensitive method
      for the identification of the presence of male epithelial cells in the postcoital
      vagina.

PMID- 12051345
TI  - Mitochondrial DNA and STR typing of matter adhering to an earphone.
AB  - STR typing and mitochondrial DNA (mtDNA) sequencing were performed on the matter
      adhering to an earphone found at a crime scene. Experimental studies were carried
      out using the earphones provided by volunteers. By means of immunohistochemistry,
      keratinocytes and a portion of nucleated epithelial cells were proven to exist in
      the contents from the earphones. DNA was extracted by means of the
      phenol/chloroform method, and the low quantity of extracted DNA was found to be
      highly degraded. Six STR loci, CSFIPO, TPOX, TH01, F13A01, FESFPS and vWA, were
      PCR amplified and typed by using two triplex systems (CTT and FFv Multiplexes,
      Promega, WI), and an amelogenin locus was determined as well. Although partial
      profiles were observed in some experimental samples, all STR loci could be typed
      when a considerable amount of high molecular weight DNA was obtained (>0.5
      ng/microL). Amplification and sequencing of mtDNA hypervariable region I(15997
      16401) and hypervariable region 11(29-408) were all successful. The mitochondrial
      DNA sequence of the actual case sample, comprising two hypervariable regions and
      a total of 785 base pairs, showed eight mutations and two insertions with respect
      to the standard published reference sequence. The genotype was unique in the
      three published Japanese databases. These results suggest that it is possible to
      analyze mtDNA from minute amounts of materials and from degraded materials more
      effectively and routinely in forensic practice.

PMID- 12051346
TI  - The use of amalgam powder and calcium hydroxide to recreate a radiopaque image of
      a lost dental restoration.
AB  - Radiographs of dental restorations are highly reliable when used to identify
      postmortem dental remains. A problem exists if key dental restorations are
      missing or defective, which results in the loss of a comparative radiographic
      image. This article describes a simple method allowing the odontologist to
      quickly recreate a temporary radiopaque restoration. This article presents a
      method of using amalgam powder (radiopaque material) and calcium hydroxide
      (radiopaque material and transport medium for the amalgam powder) to recreate a
      radiopaque image on a tooth that has lost a dental restoration. Amalgam powder
      and calcium hydroxide is easily obtained (in any dental office), fairly clean,
      easy to manipulate, inexpensive, inert, stable, and able to be removed without
      damaging the dental remains. The amalgam powder/calcium hydroxide mixture can
      easily be re-shaped or modified to reflect the radiopaque image of the original
      restoration. Radiographic comparison of the "restored" dental remains to the
      antemortem radiographs is now possible. The use of this technique is presented in
      a case report.

PMID- 12051347
TI  - The combined use of pollen and soil analyses in a search and subsequent murder
      investigation.
AB  - This case report shows how soil analyses (particularly petrology) can be used in
      conjunction with pollen in order to refine or strengthen an association. Soil
      samples from a car believed to have been used by the suspect in a missing persons
      case was subjected to soil and pollen analyses. The soil characteristics and
      petrology were used to redefine the search area using geology and soils maps, the
      pollen and vegetative remains were used to target woodlands with a particular
      species mix. As a result two bodies were located and the environmental evidence
      was used in the subsequent trial. In this case the history of the vehicle was
      well known and the wheel arches and footwells provided reliable soil traps. The
      advantage of combining the techniques is that soil evidence (both mineralogy and
      other inclusions) provides a geological/soils match while the pollen provides
      independent evidence of vegetation type providing a combination that may be rare
      or unique.

PMID- 12051348
TI  - Screen-printing ink transfer in a sexual assault case.
AB  - Yellow plastic-like particles were discovered on the clothing and body of a
      sexual assault victim. These particles were later associated to an athletic
      jersey with flaking yellow screen-printed numbers and letters, worn by the
      suspect. Depending on its intended substrate, screen-print ink can vary in color
      and composition. Particles dislodged from screen-printed garments may exhibit
      fabric impressions. Screen-printed clothing, commonly encountered in forensic
      casework, should be viewed as a potential source of trace evidence.

PMID- 12051349
TI  - Identification of tiny and thin smears of automotive paint following a traffic
      accident.
AB  - Three complementary methods in the order of stereomicroscopy, micro-FT-IR
      spectroscopy and solubility tests were used for the purpose of matching known and
      questioned paint samples in an auto accident case. Grayish green paint smears
      scattered on a silvery gray coated plastic bar were taken from a blue car and
      referred to as questioned samples. Green paint chips were collected as known
      samples from a green car. These were analyzed to determine whether the paint
      smears found in the blue car could have been the transfers from the green car.
      Although each of the three methods, when used alone, suffered from unequal bases
      for making comparison (i.e., layering whole paint vs. smeared paint),
      insufficient specificity of methodology and the interfering background coating
      beneath the smeared paint, the limitations were significantly relieved when three
      methods were used in combination. Based on the results presented in this report,
      the questioned grayish green paint smears collected from the blue car and the
      known green paint chips from the green car are of the same class of paint; that
      is, the possibility of the above stated paint transfers cannot be eliminated.

PMID- 12051350
TI  - Unusual contact marks: connecting the hubcap to the wheel of the car.
AB  - A case of homicide and attempted homicide is described. The comparison of tire
      marks linked the suspect's vehicle to the scene of crime only with low certainty.
      However, the comparison of the pressure mark on the hubcap found at the scene,
      with the balance weight on one of the wheels of the suspect's car, connected the
      suspect to the scene of crime with high certainty.

PMID- 12051351
TI  - The identification of stolen paintings using comparison of various marks.
AB  - Several oil paintings, suspected of being stolen, were found in the possession of
      an art dealer in Tel-Aviv, Israel. The authors were asked to determine if these
      paintings were the stolen ones, based on photographs, stretchers, and frames
      submitted by the alleged owners in France. A physical match was found between two
      of the questioned paintings and two stretchers. Another painting was identified
      as being previously affixed to the original frame by several nails. The fourth
      painting was identified as being the one photographed by the alleged owner. This
      identification was done by comparing micro-topography marks revealed by the
      illumination conditions of that photograph and of the questioned painting.

PMID- 12051352
TI  - Sudden death due to undiagnosed Wilms' tumor in an adult.
AB  - Sudden unexpected deaths due to natural causes constitute a large number of cases
      encountered by the forensic pathologist. In a majority of such cases, heart
      disease is responsible for sudden death. Rare disease entities resulting in
      sudden death are occasionally encountered and may not fit the classic
      epidemiological profile. We present a case of sudden death due to a previously
      undiagnosed Wilms' tumor (WT) in an adult. The pathology of WT is discussed, as
      is the topic of sudden death due to previously unrecognized malignancy.

PMID- 12051353
TI  - Fatal meningitis and encephalitis due to Bartonella henselae bacteria.
AB  - Bacterial infection due to Bartonella henselae commonly develops in children and
      young adults following cat/dog contacts and/or cat/dog scratches. Regional
      lymphadenopathy is its most common clinical expression. However, encephalitis and
      Parinaud's syndrome (oculoglandular syndrome) have also been reported as has
      systemic illness. A review of the international literature in all languages
      revealed no fatal complications in immunocompetent hosts. A four-year-old white
      child with no underlying illness began to have seizure-like activity. She was
      taken to a local hospital and subsequently transferred to a medical center. The
      child was treated aggressively for seizures and fever of unknown origin. However,
      her condition rapidly declined and she died without a specific diagnosis. At
      autopsy there was marked cerebral edema with no gross evidence of acute
      meningitis. Microscopic exams revealed multiple granulomatous lesions as well as
      a meningitis and encephalitis. A variety of cultures and stains were negative for
      acid fast and fungal organisms. Warthin-Starry stains of involved tissue
      including brain and liver revealed pleomorphic rod shaped bacilli consistent with
      Barronella henselae. Analysis of brain tissue with polymerase chain reaction
      (PCR) and Southern blot for the deoxyribonucleic acid (DNA) was definitive for
      DNA of Bartonella henselae bacteria.

PMID- 12051354
TI  - Unusual suicidal smothering by means of multiple loops of adhesive gummed tape.
AB  - In suicidal asphyxia smothering is very rare, especially when caused by winding
      strips of adhesive tape around the head to cover the nose and mouth. The authors
      report a very unusual case in which the deceased, a 66-year-old man, was found
      with two strips of tape wound around his head: the first, more superficial tape
      was wrapped six times and the second was wrapped nine times. Only integration of
      the crime scene data with those of the autopsy and the patient's psychological
      profile enabled identification of the event as suicide.

PMID- 12051355
TI  - Comparison of the elemental composition of office document paper: evidence in a
      homicide case.
AB  - Fraudulent substitution of a page within a multiple page document such as a will
      or business contract, the counterfeit manufacture of paper banknotes, and linking
      ransom or extortion notes have all been the focus of criminal investigations at
      one time or another. In a recent homicide investigation, document examiners were
      requested to compare a threatening letter received by a business partner of the
      deceased with paper samples seized under warrant from a suspect's house. Through
      a quantitative elemental analysis of the concentrations of nine elements (Na, Mg,
      Al, Mn, Sr, Y, Ba, La, and Ce) within the questioned and specimen documents,
      determined by inductively coupled plasma-mass spectrometry (ICP-MS), it was
      concluded that (i) the paper of the threatening letter originated from a
      different source to that of the paper seized from the suspect's house and (ii)
      all six pages of paper seized from the suspect's house originated from the same
      source. This discrimination of paper is presented as both a statistical t-test
      analysis (99.9% confidence limit) as well as construction of an elemental
      fingerprint for individual replicates within the questioned and specimen sample
      populations. This is the first reported use of the comparison of the elemental
      composition of document paper, determined by ICP-MS, to assist in a criminal
      investigation.

PMID- 12051356
TI  - Fatal and nonfatal poisoning by hydrogen sulfide at an industrial waste site.
AB  - An adult man (A) entered a pit to collect seepage at an industrial waste site in
      Japan. As he suddenly lost consciousness, three colleagues (B, C, D) entered the
      pit to rescue him. All of these men lost consciousness in the pit. Two workers (A
      and B) died soon after the accident, one worker (C) died 22 days after the
      accident, and one worker (D) survived. Since hydrogen sulfide gas was detected in
      the atmosphere of the pit, gas poisoning was suspected. Toxicological analyses of
      sulfide and thiosulfate, a metabolite of sulfide, in blood and urine of the
      victims were made using the extractive alkylation technique combined with gas
      chromatography/mass spectrometry (GC/MS). Sulfide was detected in the blood of A
      and B at levels of 0.13 and 0.11 mg/L, respectively, somewhat higher than in
      healthy persons. Thiosulfate was detected in whole blood of deceased victims A
      and B, in the plasma of deceased victim C, at concentrations of 10.53, 4.59, and
      4.14 mg/L, respectively. These values were similar to those found in fatal cases
      of hydrogen sulfide poisoning. Thiosulfate was not detected in the plasma of
      survivor D. With respect to urine samples, thiosulfate was the highest in the non
      acute death victim C (137.20 mg/L), followed by that in the survivor D (29.34
      mg/L), and low (0.90 mg/L) and not detected in the acute death victims, A and B,
      respectively. Based on these results, all four patients were victims of hydrogen
      sulfide poisoning. The concentrations of thiosulfate in blood and urine were more
      useful than that for sulfide for determining hydrogen sulfide poisoning.
      Thiosulfate in urine was the only indicator of hydrogen sulfide poisoning in the
      non-fatal victim.

PMID- 12051357
TI  - Post-cremation taphonomy and artifact preservation.
AB  - Contemporary commercial cremation is a reductive taphonomic process that
      represents one of the most extreme examples of postmortem human alteration of
      bone. The thorough reduction and fragmentation of cremated human remains often
      leaves little biological evidence of diagnostic value. Instead, non-osseous
      artifacts often provide the best evidence of the origin of the cremated remains,
      the identity of the decedent, and commingling of the remains of more than one
      individual. Once human remains have been cremated they are most commonly placed
      into a processor and reduced into small fragments and fine ash suitable for
      inurnment or scattering. The type of processor determines the size and utility of
      the particulates and artifacts available for analysis. The newest type of
      processors have changed the manner and degree of postmortem bone modification and
      altered the preservation of diagnostic bone fragments and cremation artifacts.
      This paper addresses the impact of the newest cremation procedures on forensic
      analysis of cremated remains.

PMID- 12051358
TI  - Failure to detect elevated levels of carboxyhemoglobin in infants dying from
      SIDS.
AB  - Carboxyhemoglobin (COHb) levels were determined in stored blood samples from 91
      infants diagnosed to have died from the sudden infant death syndrome (SIDS)
      (0.59+/-0.41%, excluding one outlying value of 10.83%); 48 age-matched controls
      (0.53+/-0.38%); and three individuals who died from fire related causes (41+/
      20%). No statistical differences in COHb levels were detected between blood from
      SIDS and control infants (p = 0.43).

PMID- 12051360
TI  - Allele distributions for D21 S1435 and D21S2055 loci in two Chinese populations.

PMID- 12051359
TI  - Visualization of postmortem chondrocyte damage by vital staining and confocal
      laser scanning 3D microscopy.
AB  - The present study was designed to investigate whether the combination of vital
      dyes [calcein acetomethyl ester and ethidium homodimer (LIVE/DEAD
      Viability/Cytoxicity Kit)] together with confocal laser scanning 3D microscopy
      was a suitable process to detect postmortem chondrocyte damage, and whether this
      process could be used to establish postmortem interval. Human knee cartilage from
      13 autopsies (postmortem interval from 1 day to 2.5 months) was incubated with
      the two dyes. The chondrocytes revealed intense staining according to their
      vitality. For those cases that were stored mainly at 4 degrees C there was a
      vitality of approximately 88 to 96% within the first 4.5 days, which decreased to
      58% after 6 days and to 9% after 1.5 months. After 2 days and 14 days at summer
      temperatures there were 70% and 8% vital chondrocytes respectively. Three of the
      13 cases showed that altered body and storage conditions limited the efficacy of
      the method. Initial data suggested a time and temperature dependent increase in
      cell breakdown. Under stable cooling conditions the use of vital dyes and
      confocal laser scanning 3D microscopy to measure chondrocyte loss may be a
      valuable tool for estimating the postmortem interval.

PMID- 12051361
TI  - Allele frequencies for the 13 CODIS STR loci in a sample of southern Croatians.

PMID- 12051362
TI  - Distribution of HLA-DQA1 and amplitype PM locus alleles in Aegean region of
      Turkey.

PMID- 12051363
TI  - Allele frequencies for three STR loci RT24, RT09, and BM1225 in northern New
      England white-tailed deer.

PMID- 12051364
TI  - D1S80 population data in eight predominant populations of India.

PMID- 12051365
TI  - Allele frequencies of microsatellite repeat loci in Bhargavas, Chaturvedis, and
      Brahmins of North India.

PMID- 12051366
TI  - Distribution of allele frequencies of six STR markers in north Indians.

PMID- 12051367
TI  - Evaluation of six short tandem repeat loci in forensics: north Indian
      populations.

PMID- 12051368
TI  - Y-chromosomal STR haplotypes in two population groups of Kerala in south India.

PMID- 12051369
TI  - Population database of Y-chromosomal haplotypes at five microsatellites among two
      distinct ethnic groups of western India.

PMID- 12051370
TI  - Frequency data of nine Y-chromosomal STR loci in a sample from central Spain.

PMID- 12051371
TI  - New meaning to the dichotomy between generalist and specialist views within the
      field of forensic science.

PMID- 12051372
TI  - Commentary on: Lewis LA et al. Processes involved in the development of latent
      fingerprints using the cyanoacrylate fuming method. J Forensic Sci 2001;46(2):241
      246.

PMID- 12051373
TI  - Commentary on: Telmon N, Allery J-P, Scolan V, Rouge D. Fatal cranial injuries
      caused by an electric angle grinder. J Forensic Sci 2001;46(2):389-391.

PMID- 12051374
TI  - Implantation of a new accommodative posterior chamber intraocular lens.
AB  - PURPOSE: A new, potentially accommodative posterior chamber lens (PCIOL) was
      designed based on principles elaborated by Hanna using finite element computer
      simulation methods. We report 3-month postoperative results in patients. METHODS:
      In a prospective study, 12 eyes of 12 patients (age 45 to 87 yr) underwent
      phacoemulsification for cataracts and PCIOL implantation. The PCIOL, 1 CU, has
      haptics designed for anterior optic movement following ciliary muscle
      contraction. Patients were examined postoperatively after 1 and 2 days, 1, 2 and
      6 weeks, and 3 months, and results were compared with a control group of 12 eyes
      that received standard PMMA or acrylic PCIOLs. RESULTS: Surgery was uncomplicated
      and all PCIOLs were well-tolerated and stable with good centration in the
      capsular bag. The results were (mean +/- SD [range] and median; 1 CU versus
      control PCIOL): near visual acuity (Birkhauser reading chart at 35 cm) with best
      distance correction 0.34 +/- 0.17 (0.2 to 0.6), 0.3 (J10-J1, median J7) versus
      0.15 +/- 0.07 (0.1 to 0.3), 0.15 (J16-J7, median J13), P=.001; subjective near
      point 59 +/- 10 cm (40 to 100 cm), 53.5 cm versus 93 +/- 20 cm (64 to 128 cm), 86
      cm, P=.004; retinoscopic accommodative range 1.2 +/- 0.4 D (0.63 to 1.5 D), 1.2 D
      versus 0.2 +/- 0.19 D (-0.25 to 0.5 D), 0.25 D, P < .001; decrease of anterior
      chamber depth after 2% pilocarpine 0.63 +/- 0.16 mm (0.40 to 0.91 mm), 0.63 mm
      versus 0.15 +/- 0.05 mm (0.08 to 0.20 mm), 0.17 mm, P < .001. CONCLUSIONS: The
      new PCIOL appears to be safe at short to medium term. Our results indicate
      pseudophakic accommodation secondary to focus shift with this PCIOL. Additional
      larger and long-term studies are necessary for exact evaluation of safety and
      accommodative power of this new PCIOL.

PMID- 12051375
TI  - Laser epithelial keratomileusis for myopia with the autonomous laser.
AB  - PURPOSE: To describe the refractive outcome, objective clinical data, and
      subjective patient experiences after laser epithelial keratomileusis (LASEK) at
      1, 3, and 6 months after surgery. METHODS: This was a retrospective,
      nonrandomized, comparative study of 58 LASEK-treated eyes (36 patients) with
      myopia (with and without astigmatism) between -1.50 and -14.75 D (mean -7.80 +/-
      2.90 D, median -7.90 D). Refractive surgery was performed using the Alcon Summit
      Autonomous LADAR Vision excimer laser. Manifest refraction, best-spectacle and
      uncorrected Snellen visual acuity, stability of refraction, and corneal haze were
      evaluated before surgery and up to 6 months after surgery. A group of randomly
      selected LASIK-treated eyes were compared at each time point. RESULTS: Patients
      who opted for monovision (n=12) were excluded. In the emmetropia targeted eyes
      (n=46), 45%, 83%, 85%, and 89% achieved 20/40 or better uncorrected Snellen
      visual acuity (UCVA) at 1 day, 1 week, 2 weeks, and 1 month respectively. At 6
      months, 73% (n=28) of eyes treated achieved UCVA 20/20 with 97% achieving 20/40
      or better (mean, -0.51 D). At 3 and 6 months, 71% (n=46) and 68% (n=28) were
      within +/- 0.50 D of emmetropia. The percentage of eyes that achieved UCVA 20/40
      or better at 6 months was 97% (n=28). Visually significant corneal haze was
      evident in two LASEK-treated patients (four eyes) at 6 months. No eyes lost two
      or more lines of best spectacle-corrected Snellen visual acuity. CONCLUSIONS:
      Preliminary data suggest that LASEK appears to be a safe, effective, and
      comparable alternative to LASIK, even for higher amounts of myopia. A
      prospective, randomized clinical trial is needed to better define the role of
      LASEK as it compares to other refractive procedures, specifically LASIK and PRK.

PMID- 12051376
TI  - Laser in situ keratomileusis for myopic astigmatism with the Nidek EC-5000 laser.
AB  - PURPOSE: We studied the efficacy, predictability, and safety of laser in situ
      keratomileusis (LASIK) for moderate to high simple and compound myopic
      astigmatism. METHODS: Ninety-two eyes of 46 consecutive patients who had LASIK
      for myopic astigmatism (64 eyes, astigmatism 3.00 to 9.00 D; myopia 0 to -20.00
      D), or simple myopia (28 eyes, myopia -4.00 to -20.00 D; astigmatism 0 to 0.50 D)
      were retrospectively studied. Mean baseline spherical equivalent refraction (SE)
      in the myopia group was -8.11 +/- 3.94 D and in the astigmatism group, -8.55 +/-
      4.49 D. All eyes underwent LASIK using the Nidek EC-5000 laser by the same
      surgeon. RESULTS: At 6 months after LASIK in the myopia group versus the
      astigmatism group, 24 eyes (85%) vs. 54 eyes (84%) were available for follow-up,
      12 eyes (50%) vs. 13 eyes (24%) had uncorrected visual acuity (UCVA) of 20/20, 19
      eyes (79%) vs. 44 eyes (81%) had UCVA of 20/40, 8 eyes (33%) vs. 18 eyes (33%)
      had SE within +/- 0.50 D, 15 eyes (62%) vs. 39 eyes (72%) had SE within +/- 1.00
      D, and mean SE was -1.22 +/- 1.17 D vs. -0.74 +/- 1.46 D. Mean astigmatism
      (vertexed to the corneal plane) in the astigmatism group was 2.77 D at 0 degrees
      before surgery and 0.32 D at 7 degrees at 6 months. None of the myopic eyes and
      three of the astigmatic eyes (5%) lost > or = 2 lines of best spectacle-corrected
      visual acuity. CONCLUSION: LASIK with the Nidek EC-5000 laser for myopic
      astigmatism was reasonably effective, predictable, and safe. Astigmatism was
      under-corrected with the nomogram implemented in this study.

PMID- 12051377
TI  - Laser in situ keratomileusus for mixed and simple myopic astigmatism with the
      Nidek EC-5000 Laser.
AB  - PURPOSE: To evaluate the visual and refractive results of laser in situ
      keratomileusis (LASIK) for mixed and simple myopic astigmatism using bitoric
      ablation. METHODS: A retrospective study was performed in 65 eyes of 38
      consecutive patients to evaluate uncorrected (UCVA) and best spectacle-corrected
      visual acuity (BSCVA) and cyclopegic and manifest refraction, before and 3 and 6
      months after LASIK (Moria LSK-ONE microkeratome, Nidek EC-5000 excimer laser).
      RESULTS: At 3 and 6 months after LASIK, 40 eyes of 24 patients (64.5%) were
      available for follow-up examination. Mean age was 25.9 +/- 6.6 years (range 18 to
      43 yr). Mean preoperative manifest spherical equivalent refraction was -1.40 +/-
      0.80 D (range -3.80 to +0.50 D) mean preoperative cylinder was -3.30 +/- 1.30 D
      (range -1.00 to -6.00 D). At 6 months follow-up, mean manifest spherical
      equivalent refraction was +0.30 +/- 0.46 D (range -0.38 to +1.88 D), mean
      cylinder was -0.73 +/- 0.61 D (range -2.25 to 0 D). There was a 77.8% decrease in
      astigmatism magnitude. According to vector analysis, mean achieved vector
      magnitude was 80% of intended. Fifty percent (20 eyes) had a cylinder within +/-
      0.50 D of emmetropia. Twenty-three eyes (57.5%) had a spherical component within
      +/- 0.50 D. Eighty-five percent (34 eyes) had postoperative UCVA of 20/40 or
      better. Ten percent (four eyes) lost two lines of Snellen BSCVA, whereas 35% (14
      eyes) gained one or more lines. CONCLUSIONS: Bitoric LASIK with the Moria LSK-ONE
      microkeratome and Nidek EC-5000 excimer laser was effective and safe for the
      reduction of cylinder in mixed and simple myopic astigmatism. Moderate
      undercorrection of the cylinder was evident.

PMID- 12051378
TI  - Surgically induced astigmatism after laser in situ keratomileusis for spherical
      myopia.
AB  - PURPOSE: To study risk factors for surgically induced astigmatism (SIA) after
      laser in situ keratomileusis (LASIK). METHODS: In a retrospective case control
      study of 104 eyes (52 patients) that underwent LASIK for myopia (spherical
      ablation alone), two groups were studied: 42/104 eyes with SIA, and controls
      (62/104 eyes). The main variables studied were preoperative refraction, corneal
      thickness, preoperative keratometric power, amount of ablation, ablation zone
      diameter, flap thickness, flap size, and the presence of complications. The
      effect of SIA on visual performance was also evaluated. RESULTS: The mean myopia
      for which LASIK was undertaken was -4.50 +/- 2.04 D. Mean scalar astigmatism
      induced was 0.35 +/- 0.50 D at 1 month, 0.33 +/- 0.40 D at 3 months, and 0.16 +/-
      0.60 D at 6 months. SIA based on refractive cylinder was 0.66 +/- 0.29 D at 1
      month, 0.54 +/- 0.32 D at 3 months, and 0.49 +/- 0.34 D at 6 months. Mean axis of
      vector induced astigmatism was 82.5 degrees +/- 57 degrees at 1 month, 98.86
      degrees +/- 52.4 degrees at 3 months, and 113.9 degrees +/- 62.6 degrees at 6
      months. Risk factors associated with the occurrence of SIA were preoperative
      keratometric power of >44 D [OR (95% CI); 1.97 (0.62 to 6.26)], ablation zone
      diameter of <6 mm [OR (95 % CI) 2.76; (0.6 to 12.6)], and suction ring diameter
      of 8.5 mm [OR (95% CI) 12.46; (2.0 to 77.38)]. The occurrence of SIA had no
      significant effect on uncorrected Snellen high contrast visual acuity, contrast
      sensitivity, and glare in comparison with controls. CONCLUSION: Surgically
      induced astigmatism was more likely to occur with the use of smaller suction
      rings of 8.5 mm and in ablation zones less than 6 mm. Parameters for visual
      performance were not affected by the presence of surgically induced astigmatism.

PMID- 12051379
TI  - Bilateral simultaneous laser in situ keratomileusis with the Aesculap Meditec MEL
      60 laser.
AB  - PURPOSE: To report the outcome of bilateral simultaneous excimer laser in situ
      keratomileusis (LASIK) with the Aesculap Meditec MEL 60 laser for the correction
      of myopia and hyperopia. METHODS: This retrospective study included 338 eyes of
      169 patients who had bilateral simultaneous LASIK performed by one surgeon
      (D.L.V.). RESULTS: Postoperatively, 20/20 or better visual acuity was achieved by
      78.5% (186 eyes) in the <-6.00-D group, and 55.6% (54 eyes) in the > or = -6.00-D
      group. Postoperatively, the mean spherical equivalent refraction was within +/-
      0.50 D for 78% (185 eyes) in the <-6.00-D group (range, -2.25 to +1.25 D), 55%
      (53 eyes) in the > or = -6.00-D group (range, -2.38 to +1.13 D), and one eye in
      the hyperopic group. Complications at 3 months included regression in five eyes
      (1.4%), infiltrates in six eyes (1.7%), primary undercorrection in two eyes
      (0.6%), superficial punctate keratitis in four eyes (1.1%), ten eyes (2.9%)
      underwent enhancement, two eyes (0.6%) underwent refractive lensectomy, and four
      eyes (1.1%) underwent astigmatic keratotomy 3 months postoperatively. Two eyes
      lost two lines of best spectacle-corrected visual acuity. CONCLUSION: Bilateral
      simultaneous LASIK with the Aesculap Meditec MEL 60 laser was effective and
      predictable. It was more economical and convenient for the patient than
      unilateral LASIK and binocular visual rehabilitation was rapidly restored. No
      sight threatening complications occurred in this group of patients.

PMID- 12051380
TI  - Changes in mesopic vision after photorefractive keratectomy for myopia.
AB  - PURPOSE: To evaluate the mesopic functions of excimer laser treated eyes with
      different treatment diameters and different laser beam delivery systems. METHODS:
      In Group 1, 38 eyes were treated with the Aesculap Meditec MEL 60 ArF scanning
      laser beam excimer laser. The treatment diameter was 5.0 mm. In Group 2, 38 eyes
      were treated with the Aesculap Meditec MEL 70(G-Scan) flying spot excimer laser;
      the chosen treatment diameter was 6.5 mm. In Group 3, there were 38 eyes with no
      treatment; vision was corrected only with spectacles (control group). All eyes
      had 20/20 best spectacle-corrected visual acuity before surgery, as did the
      control group. Measurements were carried out preoperatively and at 12 months
      following surgery. All eyes exhibited normal corneal wound healing, and
      subepithelial haze was <0.5 according to Hanna's scale. Mesopic functions
      (mesopic vision and glare sensitivity) were tested with the Mesoptometer II.
      RESULTS: The average preoperative refractive error in Group 1 was -3.40 D; in
      Group 2, -3.38 D; in Group 3, -3.44 D. In Group 1, 34% of the treated eyes met
      the night driving requirements (recognition at 1:5 contrast level), whereas in
      Group 2, 85%, and in Group 3, 95% of the eyes fulfilled this criteria. When
      contrast vision was tested under glare conditions in Group 1, 31.6%; in Group 2,
      80%; and in Group 3, 94.7% of the eyes identified the target orientation (Landolt
      ring) at contrast level 1:5. CONCLUSIONS: The unoperated spectacle wearers had
      better results in all tested functions. The larger 6.5-mm treatment diameter with
      the use of the flying spot laser beam delivery system resulted in better mesopic
      function and contrast vision under mesopic conditions than the smaller 5.0-mm
      diameter.

PMID- 12051381
TI  - Is abnormal focal steepening of the cornea related to persistent monocular
      diplopia?
AB  - PURPOSE: Some case reports have shown that abnormal focal steepening of the
      cornea appears to cause monocular diplopia by prismatic effect. The purpose of
      this study was to ascertain prospectively if the pattern of corneal distortion
      was related specifically to persistent monocular diplopia. METHODS: We selected
      16 visually normal eyes (controls) and two groups of volunteers in which abnormal
      focal steepening of the cornea was expected to be found: 40 eyes of 20 volunteers
      who wore rigid gas-permeable contact lenses (RGP) for myopia and 10 eyes of seven
      patients with keratoconus. New charts that consisted of white dials on a black
      background were prepared for detection and measurement of secondary images. Any
      secondary image that could not be eliminated by any trial lens correction was
      defined as a persistent secondary image, using the charts. Corneal topography
      from all subjects was classified: round or oval, symmetric or asymmetric bowtie,
      abnormal focal steepening accompanied by contact lens-induced corneal warpage or
      keratoconus, or amorphous. We analyzed the relationship between the persistent
      secondary image and the corneal topographical patterns. RESULTS: A persistent
      secondary image was detected from seven eyes of RGP wearers and all keratoconus
      eyes. All corneal topographies of the seven RGP eyes with a persistent secondary
      image showed abnormal focal steepening related to contact lens-induced corneal
      warpage. The direction of the persistent secondary image was approximately
      consistent with the location of the focal steepening as seen on the corneal
      topography. CONCLUSION: Abnormal focal steepening of the cornea that appeared to
      produce a prismatic difference between two parts of the cornea was specifically
      related to persistent monocular diplopia.

PMID- 12051382
TI  - Validation of the estimation of corneal aberrations from videokeratography in
      keratoconus.
AB  - PURPOSE: To validate the estimation of corneal aberrations from videokeratography
      against a laser ray tracing technique that measured total eye aberrations, in
      eyes without keratoconus (ie, cornea-dominated wave aberrations). METHODS: We
      measured total and corneal wave aberrations of three eyes diagnosed with
      keratoconus by slit-lamp microscopy and corneal topography: two eyes from one
      patient with early keratoconus and one eye with more advanced keratoconus. Total
      aberrations were measured with laser ray tracing. Corneal aberrations were
      obtained from corneal elevation data measured with a corneal videokeratoscope
      using custom software that performs virtual ray tracing on the measured front
      corneal surface. RESULTS: The keratoconus eyes showed a dramatic increase in
      aberrations (both corneal and total) particularly coma-like terms, which were
      3.74 times higher on average than normal. Anterior corneal surface aberrations
      and total aberrations Were similar in keratoconus. This similarity was greater
      for the early keratoconus patient, suggesting a possible implication of the
      posterior corneal surface in advanced keratoconus. CONCLUSIONS: The similarity
      found between corneal and total aberration patterns in keratoconus provided a
      cross-validation of both types of measurements (corneal topography and
      aberrometry). Both techniques were useful in diagnosing and quantifying optical
      degradation imposed by keratoconus.

PMID- 12051383
TI  - Pseudo-accommodation with intraocular lenses implanted in the bag.
AB  - PURPOSE: To evaluate the accommodation potential in eyes after intraocular lens
      in-the-bag implantation. METHODS: Fifty-one consecutive patients were included in
      the study. Group 1 included 26 eyes that had phacoemulsification with continuous
      curvilinear capsulorhexis and in-the-bag implanted foldable IOL. Twenty-five eyes
      in Group 2 had capsulotomy with extracapsular cataract extraction and were
      implanted with polymethylmethacrylate IOL. Time elapsed from surgery was at least
      6 months. There was no significant difference for age or gender between groups (P
      > .05). We measured accommodation amplitude and depth of the anterior chamber at
      distance and near fixation with an ultrasonic biometry device. The results were
      compared using the unpaired Student t-test. RESULTS: The anterior chamber depths
      while fixating at a distant object were not significantly different between
      groups (P>.05), however, at near the difference was statistically significant
      (P=.008). The change in depths between far and near fixation was significantly
      different (P=.002) and was more pronounced in the the capsulorhexis group (P <
      .001). The accommodation amplitudes in this group were significantly greater than
      in the capsulotomy group (P = .025). CONCLUSION: Patients who had uncomplicated
      small incision phacoemulsification surgery with continuous curvilinear
      capsulorhexis and in-the-bag implanted lens seemed to preserve some pseudo
      accommodation after surgery.

PMID- 12051385
TI  - Microbial keratitis after laser in situ keratomileusis.
AB  - PURPOSE AND METHOD: To review the literature on microbial keratitis reported
      after laser in situ keratomileusis (LASIK). RESULTS: Forty-one eyes have been
      reported to have microbial keratitis after LASIK. The causative organisms vary
      from gram positive bacteria to atypical mycobacteria, fungal, and viral
      pathogens. The infection is usually acquired intraoperatively, but may also be
      caused by postoperative contamination. A majority of the patients present within
      72 hours of the surgery with an acute onset of symptoms. Management of microbial
      keratitis after LASIK includes aggressive topical fortified antibiotic therapy,
      irrigation of stromal bed with antibiotic solution after lifting the flap, and
      sending the scraping of the infiltrate for microbiological evaluation. The
      keratitis heals with scarring and a best spectacle-corrected visual acuity of
      20/40 or better can be obtained in the majority of the patients. CONCLUSION:
      Microbial keratitis is a sight-threatening complication of LASIK.

PMID- 12051384
TI  - Phototherapeutic keratectomy for relief of pain in patients with pseudophakic
      corneal edema.
AB  - PURPOSE: To evaluate the therapeutic effects of phototherapeutic keratectomy in
      patients with pseudophakic corneal edema METHODS: Phototherapeutic keratectomy
      was performed in 12 eyes of 12 patients with pseudophakic corneal edema who were
      awaiting penetrating keratoplasty. All patients underwent planned corneal
      ablation of 120 microm. Examinations before and after surgery included
      uncorrected and corrected visual acuity, slit-lamp biomicroscopy, photography,
      and ultrasonic pachymetry. METHODS: A reduction in pain and a slight increase in
      visual acuity as well as a decrease in corneal thickness were found over an
      average 18-month follow-up period (range, 6 to 60 months). CONCLUSIONS:
      Phototherapeutic keratectomy reduced bullae formation, improved visual acuity
      slightly, and could be considered a valuable alternative to penetrating
      keratoplasty if surgery needs to be delayed or is contraindicated.

PMID- 12051386
TI  - Disabling ghosting after laser in situ keratomileusus.

PMID- 12051387
TI  - Maintenance of visual acuity after exposure to oleoresin capsicum spray following
      LASIK.

PMID- 12051388
TI  - Is macrophage activation syndrome a new entity?

PMID- 12051389
TI  - The incidence and clinical characteristics of Mycobacterium tuberculosis
      infection among systemic lupus erythematosus and rheumatoid arthritis patients in
      Korea.
AB  - OBJECTIVES: The aim of this study was to describe the incidence and clinical
      characteristics of Mycobacterium tuberculosis infection in SLE and RA patients in
      Korea where the prevalence rate of active pulmonary tuberculosis in a general
      population is relatively higher than in Western countries. PATIENTS: We reviewed
      the medical records of 283 SLE and 284 RA patients retrospectively and then
      assessed the incidence, risk factors, and clinical characteristics of active
      tuberculous infection. We then compared the results for the two different groups.
      RESULTS: Tuberculosis was documented in 15 SLE and 7 RA patients with an
      incidence rate of 7.9/1,000 patient-years and 2.3/1,000 patient-years,
      respectively (p = 0.003). SLE-associated tuberculosis cases included 3 of miliary
      tuberculosis, 7 of pulmonary tuberculosis (including 1 case of diffuse pulmonary
      involvement with meningitis) predominantly involving two or more lobes at the mid
      /lower lungfield, and 5 extra-pulmonary forms (joint, bone, kidney, larynx,
      pleura). All of the RA-associated tuberculosis cases were pulmonary forms with
      the majority being localized to single lobe, and only one case had a past history
      of tuberculosis, whereas a past history of tuberculosis and a longer duration of
      the underlying disease were significantly correlated with the development of
      tuberculosis in the SLE patients. Major organ involvement, the mean daily dosage
      of prednisolone, and a history of over 30 mg of daily prednisolone were not
      related to the development of tuberculosis. However, when we took only those
      patients taking corticosteroid until the diagnosis of tuberculosis for analysis,
      SLE patients with tuberculosis showed a higher daily dosage of prednisolone than
      those without tuberculosis. CONCLUSION: Taken together, the characteristics of
      tuberculosis in SLE patients were: (1) a higher incidence rate, (2) more frequent
      extra-pulmonary involvement, (3) more extensive pulmonary involvement, and (4) a
      higher relapse rate than in rheumatoid arthritis. Thus, the contributory role of
      M. tuberculosis infection in the morbidity and mortality of patients with SLE
      must be emphasized, especially in areas in which this bacteria is endemic.

PMID- 12051390
TI  - Corticotropin releasing hormone promoter polymorphisms in giant cell arteritis
      and polymyalgia rheumatica.
AB  - OBJECTIVE: Giant cell (temporal) arteritis (GCA) and polymyalgia rheumatica (PMR)
      are different but overlapping diseases of unknown etiology affecting the elderly.
      Corticotropin-releasing hormone (CRH) helps to regulate the immune response and
      maintain homeostasis during inflammatory stress. CRH promoter region
      polymorphisms in the 5'regulatory region of the CRH gene have been described. To
      investigate the possible implications of the CRH promoter polymorphisms in PMR
      and GCA susceptibility we have examined a series of patients with these
      conditions. METHODS: Sixty-two patients with biopsy-proven GCA, 86 patients with
      isolated PMR and 147 ethnically matched controls from the Lugo region of
      Northwest Spain were included in this study. Patients and controls were genotyped
      for CRH polymorphism in the 5' regulatory region of the gene at position 1273
      (alleles A1 andA2) and at position 225 (alleles B1 and B2) by PCR-restriction
      fragment length polymorphism. Allele frequencies and genotype distribution were
      evaluated by the chi-square test. RESULTS: When GCA and PMR patients were
      examined for alleles and genotypes for each CRH polymorphism no significant
      differences in frequency were found compared with controls. A higher CRH-A2
      allele frequency was observed in GCA patients with visual complications (21.4%)
      compared with controls (9.2%) and GCA cases without eye involvement [6.3%; p=
      0.017, Pcorr = 0.034, O.R: 4.1 (95% CI 1.2- 13.9)], although this was based on a
      small sample of patients with ischemic visual complications (n = 14) and should
      be interpreted with caution. No differences in CRH allele or genotype frequencies
      were observed in isolated PMR patients stratified by relapses and recurrence of
      disease symptoms. CONCLUSION: Polymorphisms in the CRH gene regulatory region do
      not appear to be associated with increased susceptibility to PMR or GCA. The CRH
      A2 allele may encode risk for the development of visual complications in GCA,
      although further studies to confirm this will be required.

PMID- 12051391
TI  - Autoantibody against ribosomal protein L14 in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To isolate a specific antibody against ribosomal protein L14 and to
      assess the relationship of this antibody with some of the clinicalfeatures in
      patients with systemic lupus erythematosus (SLE). METHODS: We screened the sera
      of SLE patients by immunoblotting analysis using rat total ribosomal proteins as
      antigen to determine whether sera had antibody activity against ribosomal
      proteins other than the P S10, and L12 proteins. The sera from 2 patients had
      antibody activity against a 30-kDa ribosomal protein. This antigenic protein was
      identified to be ribosomal protein L14 by two-dimensional gel electrophoresis and
      immunoblotting, so the antibody against L14 was tested by immunoblotting analysis
      using glutathione-S-transferase fusion human-L14 protein (GST-L14) as the
      antigen. We examined sera from 126 patients with SLE, and as controls sera from
      67 patients with dermatomyositis and polymyositis (DM/PM), 71 patients with
      systemic sclerosis (SSc), and 74 healthy donors. RESULTS: Antibody activity
      against GST-L14 was detected in 7 out of 126 SLE, but not in any of the DM/PM,
      PSS, or healthy controls. CONCLUSION: Antibody against ribosomal protein L14 was
      specifically detected in sera from patients with SLE. Although this antibody
      activity was not so prevalent in the patients with SLE, it might be one of the
      useful tools for diagnosis of SLE.

PMID- 12051392
TI  - Differences in understanding and application of 1987 ACR criteria for rheumatoid
      arthritis and 1991 ESSG criteria for spondylarthropathy. A pilot survey.
AB  - OBJECTIVES: To determine areas of agreement and disagreement among experts in the
      interpretation of the published criteria for RA (ACR) and spondylarthropathies (
      ESSG). METHODS: Thirty-two experts (16 from France and 16 from 10 other
      countries) replied anonymously to a mailed questionnaire. RESULTS: Tenosynovitis
      and 'sausage-like' painless swelling of the toes were considered as criteria for
      RA by 18 and 14 experts, respectively. The definition of symmetry differed widely
      among experts (symmetry of only one group of joints was sufficient for 13).
      Twenty-five experts considered erosions of other joints than the wrists and
      fingers as a criterion for RA, 17 thought that fulfilment of criteria could be
      achieved cumulatively, and 19 would appreciate clarifications of the current
      criteria. Among possible clarifications for RA, it was frequently recommended
      that morning stiffness and nodules be eliminated and that new marker antibodies,
      X-rays of the feet, and exclusion criteria be added. Twenty-three of the 29
      experts who gave an opinion (79%) agreed with the notion of SP in the absence of
      axial signs and sacroiliitis, 26/31 (84%) indicated that a patient can have both
      RA and SP, and 19/30 (63%) thought that RA and SP could be regarded as syndromes
      more than diseases. Only 5/32 experts relied more on the criteria than on their
      clinical judgement in diagnosing RA. CONCLUSIONS: There would seem to be a
      needfor the optimisation of RA and ESSG criteria, particularly within the context
      of early arthritis.

PMID- 12051394
TI  - Prevalence of HTLV-I Tax in a subset of patients with rheumatoid arthritis.
AB  - OBJECTIVE: In regions of the world where the human T cell lymphotropic virus type
      I (HTLV-I) is endemic, it is recognized that infection with this virus is
      associated with autoimmune diseases such as rheumatoid arthritis (RA). Moreover,
      mice transgenic for the HTLV-I Tax gene develop a disease akin to RA. The
      observation that about 8% of healthy American blood donors carry HTLV-I Tax in
      their lymphocytes (1) prompted studies to determine whether Tax positivity is
      more prevalent among patients with RA and if so, whether its sequence is
      homologous with prototypic HTLV-I Tax. This proved to be the case. Of 102
      patients with RA tested, one was a carrier of HTLV-I and 25 had the Tax sequences
      in their mononuclear cells and antibodies to p40 Tax in their sera, while being
      negative for antibodies to the structural proteins of the virus. METHODS: Blood
      was collectedfrom 102 RA patients. Lysates of their mononuclear cells were
      assayed for HTLV-I Tax by PCR/Southern analysis, and in some positive cases Tax
      sequence analysis was performed. Antibodies to p40 Tax, the gene product of the
      Tax sequence, were detected by western blot assay using recombinant p40 Tax as
      antigen. Results Of the 102 patients tested, one proved to be a carrier of the
      virus, having antibodies and sequences for the viral structural proteins, gag and
      env in addition to p40 Tax. Twenty-five of the 101 HTLV-I/II seronegative
      patients carried both HTLV-I Tax sequences in their mononuclear cells and had
      antibodies to p40 Tax. Sequence analysis confirmed homology with HTLV-I Tax.
      CONCLUSION: The data show that the prevalence of HTLV-I Tax positivity among
      patients with RA is -3 times higher than among healthy blood donors. Since Tax is
      known to be involved in the development of numerous autoimmune diseases, the
      possibility that it is responsible for the development of RA in a subpopulation
      of patients with this disease is not remote.

PMID- 12051393
TI  - Study to determine the presence of antipolymer antibodies in a group of Dutch
      women with a silicone breast implant.
AB  - OBJECTIVE: To determine whether there exists a population of Dutch women with a
      high prevalence of antipolymer antibodies (APA) and severe health
      complaints/symptoms, and exposure to a silicone breast implant (SBI). As the
      antigen-specific nature of the antipolymer antibody has not yet been established,
      we refer to the term polymer binding immunoglobulins. METHODS: The study
      population was selectedfrom a voluntary registry of SBI recipients of a Dutch
      consumers organisation. The final selection was based on the severity of self
      reported complaints in a questionnaire. A total of 42 SBI recipients were
      included in the study, clinically examined and blood samples were obtained.
      RESULTS: In 12 of 42 SBI recipients an increase in the level of polymer binding
      immunoglobulins was detected compared to a negative reference sample, 3 of these
      12 showing a positive and 9 a weakly positive response. In 3 out of 12 non-SBI
      recipients, included for control on the performance of the APA assay, an
      increased level of polymer binding immunoglobulins was demonstrated, 2 of these 3
      showing a positive and 1 a weakly positive response. The study population of SBI
      recipients was categorised in severity subgroups (limited, mild, moderate,
      advanced) based on the fuctional capacity and the physicians general assessment
      of pain and disease activity. Most (34 of 42) SBI recipients belonged to the
      limited severity subgroup. CONCLUSION: Our methods failed to select a group of
      severely symptomatic Dutch SBI recipients reported to have a high prevalence of
      polymer binding antibodies. A discrepancy was present between the self reported
      severe complaints and the observed mild clinical symptoms. In the group of SBI
      recipients with self reported severe complaints recruited we did not find a high
      prevalence of polymer binding immunoglobulins. SBI exposure (mean 17 years) did
      not result in induction of polymer binding immunoglobulins in this minimal
      symptomatic study group.

PMID- 12051395
TI  - The femoral distal epiphysis of ovariectomized rats as a site for studies on
      osteoporosis: structural and mechanical evaluations.
AB  - OBJECTIVE: To investigate in detail the mechanical and structural characteristics
      of cancellous bone from the femoral distal epiphysis of normal and ovariectomized
      rats, and to provide reference values in order to improve experimental research
      on osteoporosis by characterising an alternative and complementary anatomic site.
      METHODS: 40 female Sprague-Dawley rats (10 months old) were randomly divided into
      4 groups of 10 each: baseline, ovariectomized (Ovx), sham-operated (Sham-Ovx) and
      sham-aged (Sham-Aged). Baseline animals were sacrificed at the beginning of the
      study. Ovx and Sham-Ovx animals were sacrificed 16 weeks after surgery, whereas
      Shamaged rats were killed when aged 14 months. Femurs were excised and
      densitometric, ultrasonographic, mechanical and histomorphometric analyses were
      performed. RESULTS: When comparing the Ovx group with the others,
      ultrasonographic and densitometric measurements showed significant decreases (p <
      0.0005) amounting to 3-5% in the amplitude dependent speed of sound (AD-SOS) and
      13-20% in the BMD, respectively. Significant decreases were also seen in the
      femoral condyle Max. Load (28-31%; p < 0.0005) and Elastic Modulus (19-25%; p <
      0.005) in the Ovx group in comparison with the Sham-Ovx and Sham-Aged groups.
      Histomorphometric analysis showed a significant cancellous bone loss (p <
      0.0005). Densitometric (p < 0.01), histomorphometric (p < 0.01) and mechanical (p
      < 0.05) parameters were correlated with AD-SOS. Among the histomorphometric
      parameters, stepwise regression analysis showed that the trabecular bone volume
      (BV/TV) and Max. Load correctly predicted AD-SOS (p < 0.0005) and BMD (p <
      0.0005). CONCLUSION: The data from this study characterize osteopenia occurring
      in the rat distalfemur 16 weeks after ovariectomy and provide methodology and
      reference values forfurther investigations on osteoporosis and bone-implant
      osteointegration in osteopenic bone.

PMID- 12051396
TI  - IL-6 promoter polymorphism at position -174 modulates the phenotypic expression
      of polymyalgia rheumatica in biopsy-proven giant cell arteritis.
AB  - OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are
      related diseases in which diverse genetic and environmental factors are
      implicated. Both GCA and PMR are characterized by an intense acute phase
      reaction. In these sYndromes the increased production of IL-6 has been observed.
      To investigate further the genetic influence of IL-6 in GCA and PMR we have
      examined the IL-6 promoter polymorphism (G to C) at position -174 in the 5'
      region in a series of patients from Northwest Spain diagnosed with GCA and/or
      PMR. METHODS: Sixtxy-two biopsy-proven GCA patients (30 of them with associated
      PMR) and 84 patients with isolated PMR were studied. Patients and ethnically
      matched controls (n = 124) were from the Lugo region (Galicia, Northwest Spain).
      Patients and controls were genotyped for HLA-DRB1 and IL-6 polymorphism at
      position -174 by molecular methods. RESULTS: IL-6-174 allele C was marginally
      increased infrequency in GCA patients with PMR manifestations compared with
      isolated GCA (Pcorr 0.06; OR = 2.3). The increase in the frequency of the CC
      genotype in GCA patients with PMR versus those with isolated GCA was
      statistically significant (Pcorr 0.02). The increased frequency of allele C in
      GCA patients with PMR was more commonly observed in HLA-DRBI *04 negative
      patients. However, this polymorphism was not associated with a higher risk of
      ischemic events in GCA or with relapses in PMR. CONCLUSION: Allele C at position 
      174 in the 5' promoter region of the IL-6 gene may be associated with PMR in
      biopsy-proven GCA patients not carrying HLA-DRBI *04 alleles.

PMID- 12051397
TI  - Evaluation of amplicor chlamydia PCR and LCX chlamydia LCR to detect Chlamydia
      trachomatis in synovial fluid.
AB  - OBJECTIVES: PCR has been successfully used in research for the detection of C.
      trachomatis DNA in synovial samples. However, each research laboratory has
      developed its own PCR, making inter-laboratory comparisons difficult. To allow
      for standardization we evaluated two commercially available amplification systems
      originally designed for the examination of urogenital samples (Roche Amplicor
      Chlamydia PCR and Abbott LCX Chlamydia LCR), using them to analyse spiked and
      clinical synovial fluid (SF) samples from reactive arthritis (ReA),
      undifferentiated arthritis (UA), and rheumatoid arthritis (RA) patients. We
      compared their sensitivity in assays of clinical SF samples with our in-house
      developed C. trachomatis specific nested PCR. METHODS: SF was spiked with
      purified C. trachomatis elementary bodies (EB) and analyzed by the commercial
      assays. Clinical SF samplesfrom ReA (n=21), UA (n=79) and RA (n=50) patients were
      examined by the two commercial assays and our in-house PCR. RESULTS: Using SF
      samples spiked with defined numbers of C. trachomatis EB, the sensitivity of the
      commercial tests was high and similar to published PCR sensitivity. In clinical
      SF specimens the commercial assays was also able to detect CT; however, the in
      house PCR was more sensitive. Out of 10 PCR-positive SF samples Amplicor tested
      positive in only 4/10 and LCX in only 3/10. The in-house PCR detected chlamydial
      DNA in synovialfluidfrom 5/21 ReA (24%), 5/79 UA (6%) and in none of the 50 RA
      patients. CONCLUSION: Commercial amplification assays allow the detection of C.
      trachomatis in clinical specimens, although with a lower sensitivity than
      optimized PCR. Potential explanations are discussed.

PMID- 12051398
TI  - Mononuclear cell response to enterobacteria and Gram-positive cell walls of
      normal intestinal microbiota in early rheumatoid arthritis and other inflammatory
      arthritides.
AB  - OBJECTIVE: To study whether enterobacteria and Gram-positive bacterial cell walls
      (BCW) derivedfrom normal intestinal microbiota are involved in the
      etiopathogenesis of early rheumatoid arthritis (RA). METHODS: Peripheral blood
      mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) were
      isolatedfrom patients with early RA (the average duration of 5 months) and the
      controls (other types of inflammatory arthritis). The mononuclear cell
      proliferation and tumor necrosis factor-alpha (TNF-alpha) responses to heat
      killed Salmonella enteritidis (SE). Yersinia enterocolitica (YE), and Escherichia
      coli (EC), and to Gram-positive BCW derived from four common intestinal
      indigenous bacteria, Eubacterium aerofaciens (EA), Eubacterium limosum (EL),
      Lactobacillus casei (LC), and Lactobacillus fermentum (LF), and a BCW derived
      from a pathogen, Streptococcus pyogenes (SP) were investigated. RESULTS: 39% or
      56% of patients with early RA showed significant proliferation responses by PBMC
      or SFMC against enterobacteria, respectively. In other types of arthritis,
      corresponding figures were 59% or 66%. When BCW were used as antigens, 8.1% or
      23% of patients with early RA showed proliferation responses by PBMC or SFMC,
      respectively. In other types of arthritis the corresponding figures were 7.5% or
      35%, respectively. However, TNF-alpha production by SFMC stimulated by EA BCW,
      SE, YE or EC, was significantly higher in early RA than in other types of
      arthritis. CONCLUSION: These results suggest that SFMC reacting with
      enterobacteria or BCW exist in some patients with early RA, but also in other
      types of inflammatory arthritis. Intestinal bacterial agents may play a role in
      the etiopathogenesis of RA, but the effect appears to be non-specific.

PMID- 12051399
TI  - Renal tolerability of three commonly employed non-steroidal anti-inflammatory
      drugs in elderly patients with osteoarthritis.
AB  - OBJECTIVE: The primary endpoint of this study was to compare the renal
      tolerability of amtolmetin guacyl (AMG), diclofenac and rofecoxib in elderly
      patients with symptomatic osteoarthritis (OA). The assessment of efficacy was the
      secondary endpoint. METHODS: 90 patients who satisfied the American College of
      Rheumatology classification criteria for hand, hip or knee OA were randomly
      assigned to 3 treatment groups receiving either: AMG 1,200 mg over thefirst 3
      days and and 600 mg/day thereafter; diclofenac 150 mg/day; or rofecoxib 25 mg/day
      for 2 weeks. At baseline and after therapy patients were clinically assessed by
      the same examiner who was unaware of the treatment arm assignement. Serum and
      urinary parameters of renal function and the outcome measures of efficacy were
      evaluated before (t(0)) and after therapy (t(1)). RESULTS: Diclofenac produced a
      significant reduction in creatinine clearance (t(0) = 88.93 +/- 11.59; t(1) =
      75.90 +/- 16.32; p: < 0.001) and in the daily urine volume (t(0) = 1,337.93 +/-
      202.07; t(1) = 1,027.59 +/- 249.14; p: < 0.001). In the same treatment group a
      significant increase in serum creatinine, blood urea nitrogen, uric acid and
      potassium were observed. Rofecoxib treated patients showed a significant increase
      in body weight (t(0) = 75.31 +/- 4.26; t(1) = 76.54 +/- 4.84; p: < 0.001),
      systolic blood pressure (t(0) = 144 +/- 10.86; t(1) = 154 +/- 11.8; p < 0.001),
      diastolic blood pressure (t(0) = 80 +/- 6.05; t(1) = 89 +/- 7.66; p < 0.001) and
      serum sodium (t(0) = 138.73 +/- 1.28; t(1) = 140.12 +/- 1.80; p < 0.005)
      associated with a significant decrease in the daily urine volume (t(0) = 1294.64
      +/- 205.21; t, = 1,115.48 +/- 238.47; p < 0.001) and creatinine clearance (t(0)=
      86.73 +/- 8.14; t(1) = 83.15 +/- 7.96; p < 0.01). No significant changes in the
      clinical and humoral parameters were recorded in AMG treated patients. Diclofenac
      was more efficacious than the other 2 drugs (p < 0.001). No differences were
      observed between AMG and rofecoxib. Side effects related to altered kidney
      function were significantly higher in the rofecoxib group (p < 0.005).
      CONCLUSION: Diclofenac mainly impaired blood renal flow and the
      glomerularfiltration rate, while rofecoxib negatively influenced the renal sodium
      water exchange. AMG demonstrated a renal sparing effect, although the eract
      mechanism is unclear

PMID- 12051400
TI  - Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients.
AB  - OBJECTIVES: This study investigated whether: (i) rheumatoid arthritis (RA)
      patients have more micronuclei (MN) than healthy controls; (ii) methotrexate
      (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic
      acid supplementation decreases the number of MN in MTX treated patients. METHODS:
      MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA
      patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls.
      MTX treated RA patients were then randomly placed in a cross-over design to
      receive folic acid supplementation, and MN assays were repeated after 6 weeks.
      RESULTS: The MTX-RA patients had a mean age of 46 +/- 10 yrs and a mean disease
      duration of 12 +/- 9 yrs; 80% were women. The MTX dose range was 8.7 +/- 1.5
      mg/week and the mean duration of use was 16 +/- 18 months. In the non-MTX RA
      group, the mean age was 48 +/- 14 yrs, the mean disease duration was 13 +/- 9
      yrs, and 87% were women. At baseline, the number of MN were significantly higher
      in RA patients as compared with controls (3.31 +/- 2.3 vs 0.8 +/- 0.8, p <0.001).
      No difference in MN numbers was observed between users and non-users of MTX.
      Folic acid supplementation did not decrease the MN number in the MTX treated RA
      patients. CONCLUSIONS: Genotoxicity, as assessed by the MN assay, is increased in
      RA patients. These results suggest that genotoxicity is associated with RA itself
      and not with MTX use. Folic acid supplementation had no effect on the number of
      MN.

PMID- 12051401
TI  - Interleukin-13 in autoimmune rheumatic diseases: relationship with the
      autoantibody profile.
AB  - OBJECTIVE: Several cytokines play a role in the production of autoantibodies such
      as RF and ANA by B-lymphocytes; the role of IL-13 in this process has not been
      previously studied. We investigated the relationship between the serum
      concentration of this cytokine and circulating autoantibodies. METHODS: IL-13
      serum levels, as well as RF and ANA, were evaluated in 282 patients with
      autoimmune rheumatic diseases including RA (n=84), SLE (n= 114), SS (n=52) and
      Scl (n=32). RESULTS: Serum levels of IL-13 (pg/ml) were significantly higher in
      patients with RA (p < 0.00003), SLE (p < 0.03), SS (p < 0.0007), or Scl (p <
      0.025) compared to controls. IL-13 serum levels correlated with those of RF in RA
      (p < 0.00001), SLE (p < 0.003) and Scl (p < 0.03). IL-13 levels were higher in RA
      (p<0.0003), SLE (p<0.005) and Scl (p<0.05) patients with RF than in patients
      without RF. SS patients with antiSSA/Ro antibodies had significantly higher IL-13
      levels than SS patients without this autoantibody (p < 0.04). No statistically
      significant correlation was found between IL-13 levels and any other antinuclear
      autoantibody, total immunoglobulin levels or the main clinicalfeatures of each
      disease. CONCLUSION: The evidence of higher IL-13 levels in our RA, SLE, SS and
      Scl patients confirms that this cytokine is involved in the pathogenesis of
      autoimmune rheumatic diseases. The relationship of this cytokine with RF in RA,
      SLE and Scl, as well as with antiSSA/ Ro antibody in SS, strengthens the
      hypothesis that it plays a role in autoantibody production. However, the
      different autoantibody synthesis by B-cells recognises different pathways
      depending on the underlying autoimmune disease.

PMID- 12051402
TI  - Anthrax vaccination and joint related adverse reactions in light of biological
      warfare scenarios.
AB  - OBJECTIVES: The purpose of this analysis was to evaluate anthrax vaccine (AVA)
      and joint related adverse reactions based upon analysis of the VAERS database in
      light of the current possibility of the use of anthrax as a biological warfare
      agent. METHODS: A certified copy of the VAERS database was obtainedfrom the CDC.
      In this study, we conducted a retrospective analysis using Microsoft Access for
      all joint attributed adverse reactions reported following anthrax vaccination.
      The employment of chi-square analysis determined if the elevated incidence rates
      of associated adverse reactions in anthrax vaccine recipients were statistically
      significant. RESULTS: Our analysis shows a very large and statistically
      significant increase in joint symptoms following vaccination with AVA when
      compared to our control population consisting of adverse joint reactions reported
      following vaccination with hepatitis A vaccine and Td vaccine. CONCLUSION: We
      believe that civilian doctors need to become familiar with the adverse reactions
      that can be expected to follow the use of AVA. Both civilian and military doctors
      need to be vigilant in reporting all such reactions to VAERS, so that more
      information can be gathered about AVA. We also believe that an anthrax vaccine
      with an improved safety profile is needed if it is to be used in populations,
      either military or civilian, that are not under imminent threat of attack by
      biological warfare agents. It should also be kept in mind that the widespread use
      of anthrax vaccination may cause potential producers of biological weapons and
      terrorists to seek to produce anthrax strains that are not neutralized by the
      current vaccine.

PMID- 12051403
TI  - The association of serum matrix metalloproteinases and their tissue inhibitor
      levels with scleroderma disease severity.
AB  - OBJECTIVE: Matrix metalloproteinase 3 (MMP-3) is reported to play an important
      role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid
      arthritis (RA). Studies have also investigated the association of different
      tissue inhibitors of MMPs (TIMPs) with fibrosis in scleroderma (SSc). The aim of
      this study was to evaluate the correlation of serum MMP-1, 3 and TIMP-1 with
      severity and disease specific markers of SSc and RA. METHODS: Serum MMP-1,3 and
      TIMP-1 were measured in 42 SSc patients (age range 28-68 yr mean 47 yr) and
      compared to 29 RA and 30 healthy age- and sex-matched individuals. Elevated
      values of MMPs and TIMP-1 were defined as those greater than 2 SD above the
      normal mean. All SSc and RA patients were scored for disease severity. RESULTS:
      Serum MMP-1 was significantly elevated in 8/42 (19%) SSc patients (p = 0.01) but
      only in 2/29 (7%) RA patients (p = 0.2). Whereas MMP-3 levels were elevated in
      10/29 (34%) RA patients (p = 0.002), it was elevated in only 5/42 (12%) SSc
      patients (p = 0.03). TIMP-1 was found elevated in 17/42 (40%) SSc patients (p =
      0.001) and in only 4/29 RA patients (with a strong trend towards significance, p
      = 0.052). We found a significant association between the elevation of both MMPs
      and TIMP-1 levels, with the severity of SSc. Those who had an increase of more
      than one MMP and/or TIMP, demonstrated life-threatening major organ involvement
      such as end stage lung fibrosis, GI aperislasis, and severe cardiacfailure.
      Contrary to that in SSc, the severity of RA showed some trend of association with
      MMP-3 only. CONCLUSION: We confirm previous observations that MMPs and TIMPs may
      play an important role in various rheumatic diseases. Whereas serum increase of
      MMP-3 correlated with RA severity, SSc severity was more characterized by the
      increase of both MMP-1 and TIMP-1. This suggests that the MMPs and TIMPs involved
      in SSc are different than those playing a role in RA, which may indicate that in
      SSc they are produced in different locations than in RA.

PMID- 12051404
TI  - Severe cutaneous vasculitis following intravenous infusion of gammaglobulin in a
      patient with type II mixed cryoglobulinemia.
AB  - Intravenous infusion of gammaglobulins (IVIG) is one of the treatments of choice
      in patients with type II mixed cryoglobulinemia (MC). We describe the case of a
      patient with MC who suffered an adverse generalised reaction with severe
      cutaneous vasculitis accompanied by a sudden increase in cryocrit levels shortly
      after being treated with IVIG. When the same gammaglobulin preparation was added
      in vitro to a sample of the patient's serum, a strong increment in cryoglobulin
      precipitation and depletion of the monoclonal IgM peak resulted. We suggest that
      this simple method of studying the displacement of the precipitation reaction
      could help to predict the outcome of treatment and must be performed before
      starting IVIG in patients with MC.

PMID- 12051405
TI  - Involvement of the thoracic spine in tophaceous gout. A case report.
AB  - The presence of tophi involving the spine is an atypical complication of
      tophaceous gout and its diagnosis may be difficult. The authors present a case of
      tophaceous gout involving the thoracic spine and discuss the topic.

PMID- 12051406
TI  - Sarcoidosis in the pediatric age.

PMID- 12051407
TI  - Different circulating lymphocyte profiles in patients with different subtypes of
      juvenile idiopathic arthritis.
AB  - OBJECTIVE: To determine the immunophenotypic profiles of circulating lymphocytes
      in patients with different disease types of Juvenile Idiopathic Arthritis (JIA).
      METHODS: Peripheral blood lymphocyte subsets from 19 patients with oligoarticular
      JIA (o-JIA), 10 patients with polyarticular JIA (p-JIA), 12 patients with
      systemic JIA (s-JlA) andfrom 41 age-matched healthy controls were characterized
      by two color immunofluorescence flow cytometry analysis. RESULTS: Patients with o
      JIA and p-JIA had increased numbers of HLA-DR+ Tcells and Tcells co-expressing
      CD57 and CD16/56, indicating T cell activation and terminal differentiation of
      CD8+ T cells respectively. By contrast, in patients with s-JIA there was no
      increase in the activation or differentiation markers on T cells, but a profound
      decrease in circulating NK cells. All patients had hypergammaglobulinemia
      consistent with B cell hyperactivity, but increased numbers of CD5+ B cells were
      found only in o-JIA and p-JIA. CONCLUSION: Distinct immunophenotypic lymphocyte
      profiles in patients with o-JIA and p-JIA compared to patients with s-JIA as
      demonstrated in this study, are consistent with afundamental heterogeneity of the
      disease.

PMID- 12051408
TI  - Soluble adhesion molecules ICAM-1 and E-selectin in juvenile arthritis: clinical
      and laboratory correlations.
AB  - OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of soluble
      intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in patients
      with active juvenile idiopathic arthritis (JIA) and in paediatric controls and
      correlate them with clinical and laboratory variables. METHODS: Total of'30 JIA
      patients were evaluated: 15 with polyarticular disease course (JIA-poly) and 15
      with oligoarthritis (JIA-oligo). Paediatric age-matched control groups consisted
      of 11 Henoch-Schonlein purpura (HSP) and 10 febrile patients (FC) and 28 healthy
      children (HC). Current medication, the erythrocyte sedimentation rate (ESR), C
      reactive protein (CRP) and full blood count (FBC) were recorded. Soluble ICAM-1
      and E-sel in serum and SF were measured by a sandwich ELISA kit. RESULTS: In the
      JIA-poly group the concentration of ICAM-1 was significantly higher than in
      healthy (p < 0.01), but notfebrile controls. Both ICAM-1 and E-selectin
      correlated with the active joint count (p < 0.01). In 13 JIA patients no
      correlanon was found between SF ICAM-1 and E-sel levels and the SF leucocyte
      counts. No significant differences were seen in the disease control and JIA-oligo
      groups compared to HC. A significant negative correlation with age was observed
      for the group as a whole (ICAM-1: p < 0.05, E-sel: p < 0.01); E-sel correlated
      with the leucocyte and thrombocyte counts (p < 0.01), and both molecules with CRP
      (p < 0.05) and with each other (p < 0.01). CONCLUSION: A high concentration of
      soluble ICAM-1 in JIA patients with polyarthritis is reported here for the first
      time. None of the patients showed signs of injection or vasculitis, where
      generalised endothelial activation could be its main source. Our finding of
      correlations between both ICAM-1 and E-sel levels and joint counts supports the
      hypothesis of their synovial origin. ICAM- I and E-sel could serve as a marker of
      aggressive disease, but their predictive value needs to be further studied.

PMID- 12051409
TI  - Observational study on intra/periarticular injections in North Jordan.

PMID- 12051410
TI  - Juvenile dermatomyositis: medical and psychosocial team approach.

PMID- 12051411
TI  - MRI diagnosis and successful treatment of upper cervical spine synovitis in a
      patient with juvenile chronic arthritis.

PMID- 12051412
TI  - Osteonecrosis of the knees in a variable common immunodeficiency.

PMID- 12051413
TI  - Detection of anticardiolipin antibodies.

PMID- 12051415
TI  - A simple formula for the Lamb modes in a plate.

PMID- 12051416
TI  - Chaotic behavior of piezoelectric plate vibration.

PMID- 12051414
TI  - Combining cyclosporine with prevailing antirheumatic drug therapy in the
      treatment of juvenile idiopathic arthritis.

PMID- 12051417
TI  - Knowledge about typical source output influences perceived auditory distance.

PMID- 12051418
TI  - Coupled-mode sound propagation in a range-dependent, moving fluid.
AB  - Full-field acoustic methods for current velocity inversion require accurate and
      efficient mathematical models of sound propagation in a range-dependent waveguide
      with flow. In this paper, an exact coupled-mode representation of the acoustic
      field is derived. To account for the physics of the problem, normal modes in a
      corresponding range-independent waveguide are chosen as the local basis. In the
      absence of currents, mode shape functions form a complete orthogonal basis. This
      property is heavily used in coupled-mode theories of sound propagation in
      motionless fluid. Unlike in the motionless case, however, vertical dependencies
      of acoustic pressure in individual normal modes are not orthogonal in the
      presence of currents. To overcome this difficulty, linearized equations of
      hydrodynamics are rewritten in terms of a state vector. Its five components are
      expressed in terms of acoustic pressure and particle displacement due to the
      wave. Orthogonality of the state vectors corresponding to individual normal modes
      is established. Coupled differential equations are derived for range-dependent
      mode amplitudes, leading to a remarkably simple result. The mode-coupling
      equations have the same form as those known for the motionless case, but of
      course the values of the mode-coupling coefficients differ as long as the range
      dependence of the flow velocity contributes to mode coupling in addition to the
      range dependence of sound speed and fluid density. The mode-coupling formulation
      is verified against known coupled-mode equations for certain limiting cases and
      an exact analytic solution of a benchmark problem.

PMID- 12051419
TI  - Scattering from impedance gratings and surface wave formation.
AB  - The scattering problem of acoustic plane waves from comb-like impedance gratings
      on a rigid surface has been investigated in this paper. A rigorous analytic
      approach for homogeneous plane-wave incidence is presented based on the
      periodicity of the grating structure, in which the problem was solved as a mixed
      boundary value problem and the scattered field was represented by the tangent
      velocity difference across a partition wall of the grating. A singular integral
      equation has been derived for the tangent velocity difference, which can directly
      be solved with the Gauss-Chebyshev procedure. The resulting solution consists of
      a series of Bloch-Floquet waves (plane bulk wave and surface wave modes) with
      explicit expressions for the expansion coefficients. When the grating period is
      much less than the incident wavelength (ka << 1), the grating structure is
      equivalent to a plane impedance surface and no surface waves can be excited with
      homogeneous plane-wave incidence. When the grating period is comparable to the
      incident wavelength, resonance phenomena are predicted under certain conditions
      and surface waves can form, even with homogeneous plane-wave incidence. The
      dispersion relation for surface waves has also been examined. The impedance
      effects of the grating on the reflection and diffraction waves as well as on the
      dispersion and formation of surface waves have been studied, with the
      acoustically hard grating being the special case of the general impedance
      grating.

PMID- 12051420
TI  - Acoustic scattering by inhomogeneous spheres.
AB  - Acoustic scattering problems are considered when the material parameters (density
      rho and speed of sound c) are spherically symmetric functions of position.
      Explicit separated solutions are derived (i) when rho(r) = exp(beta r) and c(-2)
      is a linear function of r(-1), and (ii) when rho(r) = exp(-beta r2) and c(-2) is
      a linear function of r2. In both cases, the radial parts of the solutions are
      given in terms of Coulomb wave functions or Whittaker functions; these are well
      studied special functions, closely related to confluent hypergeometric functions.
      Two problems are discussed in detail: scattering by an inhomogeneous sphere
      embedded in a homogeneous fluid, and scattering by a homogeneous sphere with a
      concentric inhomogeneous coating.

PMID- 12051421
TI  - An investigation of the influence of acoustic waves on the liquid flow through a
      porous material.
AB  - An experimental and theoretical investigation has been made of the influence of
      high-frequency acoustic waves on the flow of a liquid through a porous material.
      The experiments have been performed on Berea sandstone cores. Two acoustic horns
      were used with frequencies of 20 and 40 kHz, and with maximum power output of 2
      and 0.7 kW, respectively. Also, a temperature measurement of the flowing liquid
      inside the core was made. A high external pressure was applied in order to avoid
      cavitation. The acoustic waves were found to produce a significant effect on the
      pressure gradient at constant liquid flow rate through the core samples. During
      the application of acoustic waves the pressure gradient inside the core
      decreases. This effect turned out to be due to the decrease of the liquid
      viscosity caused by an increase in liquid temperature as a result of the acoustic
      energy dissipation inside the porous material. Also, a theoretical model has been
      developed to calculate the dissipation effect on the viscosity and on the
      pressure gradient. The model predictions are in reasonable agreement with the
      experimental data.

PMID- 12051422
TI  - Real-time nondestructive evaluation of fiber composite laminates using low
      frequency Lamb waves.
AB  - Amid the nondestructive evaluation techniques available for the inspection of
      composite materials, only a few are suitable for implementation while the
      component is in service. The investigation examines the application of Lamb waves
      at low-frequency-thickness products for the detection of delaminations in thick
      composite laminates. Surface-mounted piezoelectric devices were excited with a
      tone burst to generate elastic waves in the structure. Experiments were carried
      out on composite beam specimens where wave propagation distances over 2 m were
      achieved and artificially induced delaminations as small as 1 cm2 were
      successfully identified. The feasibility of employing piezoelectric devices for
      the development of smart structures, where a small and lightweight transducer
      system design is required, has been demonstrated. The resonance spectrum method,
      which is based on the study of spectra obtained by forced mechanical resonance of
      samples using sine-sweep excitation, has been proposed as a technique for
      measuring the A0 Lamb mode phase velocity. The finite-element method was also
      used to investigate qualitatively the dynamic response of laminates to wave
      propagation. Several locations and spatial distribution of the actuators were
      examined showing the advantages of using transducers arrays for the inspection of
      large structures.

PMID- 12051423
TI  - Experimental identification of finite cylindrical shell vibration modes.
AB  - Acoustic scattering from a finite air-filled elastic cylindrical shell, immersed
      in water, is investigated. The shell is made of stainless steel and has a
      thickness to outer radius ratio of 17%. The considered dimensionless frequency
      range extends over 7 << k1a << 22 (k1: wave number in water, a: outer radius).
      Bistatic measurements are carried out to identify vibration modes related to the
      phase matching of the first guided wave, T0, propagating on the shell. Both
      transducers, the emitter and the receiver, are positioned at the same angular
      distance with regard to the normal axis of the shell. The emitter transducer is
      fixed at a given position. In order to identify circumferential modes of
      vibration, the receiver transducer is made to rotate in the azimuthal plane,
      normal to the shell axis. Results obtained are plotted in functions of
      dimensionless frequency and azimuthal angle. Vibration modes along the shell's
      length are identified by moving the receiver transducer parallel to the shell
      axis. In this case, results are plotted in functions of dimensionless frequency
      and axial wave number. The experimental investigation is corroborated by
      theoretical results obtained from approximate calculations for thick finite
      cylindrical shells [Scot F. Morse et al., J. Acoust. Soc. Am. 103, 785-794
      (1998)]. The evolution of the mode position with respect to the incidence angle
      is discussed so as to clarify peak patterns in backscattered resonance spectra.

PMID- 12051424
TI  - Phased array element shapes for suppressing grating lobes.
AB  - Most techniques for suppressing grating lobes in phased arrays while relaxing the
      interelement spacing requirement involve redistributing array elements in sparse
      aperiodic patterns, or varying the transmit-receive beam patterns. An alternative
      is presented which uses oversized array elements to eliminate grating lobes as a
      direct consequence of the element shape. It is shown that by using carefully
      shaped, overlapping elements, maximum scan angle can be exchanged for a reduced
      interelement spacing requirement.

PMID- 12051425
TI  - Full-wave modeling of therapeutic ultrasound: nonlinear ultrasound propagation in
      ideal fluids.
AB  - The number of applications of high-intense, focused ultrasound for therapeutic
      purposes is growing. Besides established applications like lithotripsy, new
      applications like ultrasound in orthopedics or for the treatment of tumors arise.
      Therefore, new devices have to be developed which provide pressure waveforms and
      distributions in the focal zone specifically for the application. In this paper,
      a nonlinear full-wave simulation model is presented which predicts the
      therapeutically important characteristics of the generated ultrasound field for a
      given transducer and initial pressure signal. A nonlinear acoustic approximation
      in conservation form of the original hydrodynamic equations for ideal fluids
      rather than a wave equation provides the base for the nonlinear model. The
      equations are implemented with an explicit high-order finite-difference time
      domain algorithm. The necessary coefficients are derived according to the
      dispersion relation preserving method. Simulation results are presented for two
      different therapeutic transducers: a self-focusing piezoelectric and one with
      reflector focusing. The computational results are validated by comparison with
      analytical solutions and measurements. An agreement of about 10% is observed
      between the simulation and experimental results.

PMID- 12051426
TI  - Directional dependence of nonlinear surface acoustic waves in the (001) plane of
      cubic crystals.
AB  - Spectral evolution equations are used to perform analytical and numerical studies
      of nonlinear surface acoustic waves in the (001) plane of a variety of
      nonpiezoelectric cubic crystals. The basic theory underlying the model equations
      is outlined, and quasilinear solutions of the equations are presented.
      Expressions are also developed for a characteristic length scale for nonlinear
      distortion and a nonlinearity coefficient. A time-domain equation corresponding
      to the spectral equations is derived. Numerical calculations based on measured
      second- and third-order elastic constants taken from the literature are performed
      to predict the evolution of initially monofrequency surface waves. Nonlinearity
      matrix elements that indicate the coupling strength of harmonic interactions are
      shown to provide a useful tool for characterizing waveform distortion. The
      formation of compression or rarefaction shocks can be strongly dependent on the
      direction of propagation, and harmonic generation is suppressed or increased in
      certain directions.

PMID- 12051427
TI  - Energy: converting from acoustic to biological resource units.
AB  - Acoustic backscattering strength is often used as an index of biomass; however,
      the relationship between these variables has not been directly validated.
      Relationships were investigated between acoustic cross section at 200 kHz,
      measured as part of a previous study, and measured values of length, biovolume,
      dry weight, ash-free dry weight, and caloric content of the same individual
      specimens. Animals were part of the Hawaiian mesopelagic boundary community and
      included shrimps, squids, and myctophid fishes. The strong relationships found
      between all the variables measured make it possible to approximate any one
      variable from the measured values of others within a class of animals. The data
      show that for these midwater animals, acoustic scattering can be used as an index
      of biomass. Dorsal-aspect acoustic cross section at 200 kHz predicted dry weight
      and ash-free dry weight at least as well as did body length, a standard
      predictor. Dorsal-aspect acoustic cross section at 200 kHz was also a strong
      predictor of total caloric content. The relationship between dorsal-aspect
      acoustic cross section and caloric content of Hawaiian mesopelagic animals was
      linear and additive. Consequently, it is possible to directly convert acoustic
      energy from these animals to organic resource units without having knowledge of
      the size distribution of the populations being studied.

PMID- 12051428
TI  - Nonlinear two-dimensional model for thermoacoustic engines.
AB  - A two-dimensional model and efficient solution algorithm are developed for
      studying nonlinear effects in thermoacoustic engines. There is no restriction on
      the length or location of the stack, and the cross-sectional area of the
      resonator may vary with position along its axis. Reduced model equations are
      obtained by ordering spatial derivatives in terms of rapid variations across the
      pores in the stack, versus slow variations along the resonator axis. High
      efficiency is achieved with the solution algorithm because the stability
      condition for numerical integration of the model equations is connected with
      resonator length rather than pore diameter. Computation time is reduced
      accordingly, by several orders of magnitude, without sacrificing spatial
      resolution. The solution algorithm is described in detail, and the results are
      verified by comparison with established linear theory. Two examples of nonlinear
      effects are investigated briefly, the onset of instability through to saturation
      and steady state, and nonlinear waveform distortion as a function of resonator
      shape.

PMID- 12051429
TI  - Investigations of sound waves generated by the Hall effect in electrolytes.
AB  - Electrolyte ions moving in a magnetic field produce a velocity component
      transverse to the electric and magnetic fields. This phenomenon can be
      alternatively termed as the Hall effect, a magnetohydrodynamic transducer, or a
      liquid-state electromagnetic transducer. In electrolytes, the viscous drag of the
      electrolyte fluid is dominant, so the ion deflection soon reaches a terminal
      velocity dependent only on the electric field strength. The alternating velocity
      component transverse to the electric and magnetic fields produces a pressure wave
      due to the viscous drag of the fluid on the ions. Acoustic waves of very high
      frequencies can be produced since the mass of an ion is very small. Theory for
      this method of generating sound waves by ultrahigh frequency (UHF)
      electromagnetic wave impinging on a conducting medium in a magnetic field,
      causing a conduction current to flow near the surface (skin effect), is
      presented. Experiments were performed in an electrolyte at frequencies from 8 kHz
      to 1 MHz to study the effects of electrode size, ionic mobility, and ionic
      concentration. In the reciprocal effect, ions moving en masse with the particle
      velocity of a passing acoustic wave induce an alternating voltage between a pair
      of electrodes in a transverse magnetic field.

PMID- 12051430
TI  - A theoretical study of structural acoustic silencers for hydraulic systems.
AB  - Theoretical studies show that the introduction of an in-line structural acoustic
      silencer into a hydraulic system can achieve broadband quieting (i.e., high
      transmission loss). Strategies for using structural acoustic filters for
      simultaneously reducing reflection and transmission by tailoring the material
      properties are studied. A structural acoustic silencer consists of a flexible
      layer inserted into nominally rigid hydraulic piping. Transmission loss is
      achieved by two mechanisms--reflection of energy due to an impedance mismatch,
      and coupling of the incoming acoustic fluctuations to structural vibrations
      thereby allowing for the extraction of energy through losses in the structure.
      Structural acoustic finite element simulations are used to determine the
      transmission loss and evaluate designs. Results based on the interaction of
      orthotropic and isotropic plates with variable geometry, operating in heavy
      fluids like water and oil, are presented.

PMID- 12051432
TI  - Nondestructive imaging of shallow buried objects using acoustic computed
      tomography.
AB  - The nondestructive three-dimensional acoustic tomography concept of the present
      investigation combines computerized tomography image reconstruction algorithms
      using acoustic diffracting waves together with depth information to produce a
      three-dimensional (3D) image of an underground section. The approach illuminates
      the underground area of interest with acoustic plane waves of frequencies 200
      3000 Hz. For each transmitted pulse, the reflected-refracted signals are received
      by a line array of acoustic sensors located at a diametrically opposite point
      from the acoustic source line array. For a stratified underground medium and for
      a given depth, which is represented by a time delay in the received signal, a
      horizontal tomographic 2D image is reconstructed from the received projections.
      Integration of the depth dependent sequence of cross-sectional reconstructed
      images provides a complete three-dimensional overview of the inspected terrain.
      The method has been tested with an experimental system that consists of a line
      array of four-acoustic sources, providing plane waves, and a receiving line array
      of 32-acoustic sensors. The results indicate both the potential and the
      challenges facing the new methodology. Suggestions are made for improved
      performance, including an adaptive noise cancellation scheme and a numerical
      interpolation technique.

PMID- 12051431
TI  - Hearing protector attenuation: models of attenuation distributions.
AB  - Current hearing protector rating standards estimate the protection performance
      for a given frequency as the mean attenuation minus a multiple of the standard
      deviation. Distributions of real-ear attenuation at threshold data are fit with
      maximum likelihood estimation procedures using both normal and mixed-normal
      models. Attenuations from six hearing protectors, Bilsom UF-1 earmuff, Bilsom
      Quietzone, E.A.R Classic, E.A.R EXPRESS Pod Plugs, Howard Leight MAX, and Wilson
      EP100 earplugs, measured with a subject-fit protocol are reported. The mixed
      normal (bimodal) model provides a better fit to the empirical data than the
      unimodal model for most frequencies and protectors. Primarily, the bimodal model
      fits the shape of the distributions caused by data from poorly-fit protectors.
      This paper presents an alternative method for estimating the protection
      performance either with the more accurate bimodal model or directly from the
      empirical cumulative distributions of the attenuation data.

PMID- 12051433
TI  - A combination of PZT and EMAT transducers for interface inspection.
AB  - A PZT (Lead Zirconate-Titanate) transducer requires a couplant to send and
      receive mechanical waves. This requirement is a major shortcoming of the PZT
      technique for use in field applications. In the laboratory environment careful
      considerations and surface treatments are required to use PZT because the
      couplant can affect the consistency of experimental results. One alternative to
      overcome this shortcoming is the use of EMAT (ElectroMagnetic Acoustic
      Transducer). However, EMAT gives relatively low transmitted ultrasonic energy,
      with low signal to noise ratio, and the induced energy is critically dependent on
      the probe proximity to the test object. These are not desirable properties for
      NDT (nondestructive testing) of civil infrastructures. That is why, in this
      paper, a combination of PZT and EMAT is introduced for investigating reinforced
      concrete structures. Interface defects between steel bars and concrete are
      investigated by this technique. It is shown that the PZT-EMAT combination is very
      effective for steel bar-concrete interface inspection and the guided waves are
      useful for nondestructive testing of civil infrastructures.

PMID- 12051434
TI  - Factors affecting the performance of large-aperture microphone arrays.
AB  - Large arrays of microphones have been proposed and studied as a possible means of
      acquiring data in offices, conference rooms, and auditoria without requiring
      close-talking microphones. When such an array essentially surrounds all possible
      sources, it is said to have a large aperture. Large-aperture arrays have
      attractive properties of spatial resolution and signal-to-noise enhancement. This
      paper presents a careful comparison of theoretical and measured performance for
      an array of 256 microphones using simple delay-and-sum beamforming. This is the
      largest currently functional, all digital-signal-processing array that we know
      of. The array is wall-mounted in the moderately adverse environment of a general
      purpose laboratory (8 m x 8 m x 3 m). The room has a T60 reverberation time of
      550 ms. Reverberation effects in this room severely impact the array's
      performance. However, the width of the main lobe remains comparable to that of a
      simplified prediction. Broadband spatial resolution shows a single central peak
      with 10 dB gain about 0.4 m in diameter at the -3 dB level. Away from that peak,
      the response is approximately flat over most of the room. Optimal weighting for
      signal-to-noise enhancement degrades the spatial resolution minimally.
      Experimentally, we verify that signal-to-noise gain is less than proportional to
      the square root of the number of microphones probably due to the partial
      correlation of the noise between channels, to variation of signal intensity with
      polar angle about the source, and to imperfect correlation of the signal over the
      array caused by reverberations. We show measurements of the relative importance
      of each effect in our environment.

PMID- 12051435
TI  - An acoustic-logging transmission-network model.
AB  - The acoustic logging process can be described as a signal transmission system
      with a corresponding transmission network model. This model gives the relations
      between driving-voltage signal, the electrical-acoustic conversion at the source,
      acoustic properties of the propagation media (borehole fluid and formation around
      borehole), the pressure response in the borehole, the acoustic-electrical
      conversion at the receiver and recorded logging signal.

PMID- 12051436
TI  - Acoustic tracking of a freely drifting sonobuoy field.
AB  - This paper develops an acoustic inversion algorithm to track a field of freely
      drifting sonobuoys using travel-time measurements from a series of
      nonsimultaneous impulsive sources deployed around the field. In this scenario,
      the time interval between sources can be sufficiently long that significant
      independent movement of the individual sonobuoys occurs. In addition, the source
      transmission instants are unknown, and the source positions and initial sonobuoy
      positions are known only approximately. The formulation developed here solves for
      the track of each sonobuoy (parametrized by the sonobuoy positions at the time of
      each source transmission), allowing arbitrary, independent sonobuoy motion
      between transmissions, as well as for the source positions and transmission
      instants. This leads to a strongly underdetermined inverse problem. However,
      regularized inversion provides meaningful solutions by incorporating a priori
      information consisting of prior estimates (with uncertainties) for the source
      positions and initial sonobuoy positions, and a physical model for preferred
      sonobuoy motion. Several models for sonobuoy motion are evaluated, with the best
      results obtained by minimizing the second spatial derivative of the tracks to
      obtain the minimum-curvature or smoothest track, subject to fitting the acoustic
      data to a statistically appropriate level.

PMID- 12051437
TI  - A revised model of the inner-hair cell and auditory-nerve complex.
AB  - A revised computational model of the inner-hair cell (IHC) and auditory-nerve
      (AN) complex is presented and evaluated. Building on previous models, the
      algorithm is intended as a component for use in more comprehensive models of the
      auditory periphery. It combines smaller components that aim to be faithful to
      physiology in so far as is practicable and known. Transduction between cochlear
      mechanical motion and IHC receptor potential (RP) is simulated using a
      modification of an existing biophysical IHC model. Changes in RP control the
      opening of calcium ion channels near the synapse, and local calcium levels
      determine the probability of the release of neurotransmitter. AN adaptation
      results from transmitter depletion. The exact timing of AN action potentials is
      determined by the quantal and stochastic release of neurotransmitter into the
      cleft. The model reproduces a wide range of animal RP and AN observations. When
      the input to the model is taken from a suitably nonlinear simulation of the
      motion of the cochlear partition, the new algorithm is able to simulate the rate
      intensity functions of low-, medium-, and high-spontaneous rate AN fibers in
      response to stimulation both at best frequency and at other frequencies. The
      variation in fiber type arises in large part from the manipulation of a single
      parameter in the model: maximum calcium conductance. The model also reproduces
      quantitatively phase-locking characteristics, relative refractory effects, mean
      to-variance ratio, and first- and second-order discharge history effects.

PMID- 12051438
TI  - Vibration measurement of the tympanic membrane of guinea pig temporal bones using
      time-averaged speckle pattern interferometry.
AB  - "Time-averaged holography" and "holographic interferometry" enable recording of
      the complete vibration pattern of a surface within several seconds. The results
      appear in the form of fringes. Vibration amplitudes smaller than 100 nm are not
      readily measurable by these techniques, because such small amplitudes produce
      variations in gray level, but not fringes. In practice, to obtain clear fringes
      in these measurements, stimulus sound pressures higher than 100 dB SPL must be
      used. The phase of motion is also not obtainable from such fringe techniques. In
      this study, a sinusoidal phase modulation technique is described, which allows
      detection of both small amplitudes of motion and their phase from time-averaged
      speckle pattern interferometry. In this technique, the laser injection current is
      modulated and digital image processing is used to analyze the measured patterns.
      When the sound-pressure level of stimuli is between 70 and 85 dB SPL, this system
      is applied to measure the vibratory response of the tympanic membrane (TM) of
      guinea pig temporal bones at frequencies up to 4 kHz where complicated vibration
      modes are observed. The effect of the bulla on TM displacements is also
      quantified. Results indicate that this system is capable of measuring the
      nanometer displacements of the TM, produced by stimuli of 70 dB SPL.

PMID- 12051439
TI  - Re-examination of the role of the human acoustic stapedius reflex.
AB  - The "rollover" seen in the word recognition performance scores of patients with
      Bell's palsy (facial nerve paralysis) has historically been taken as an indicator
      of the role of the stapedius reflex in the protection from upward spread of
      masking. Bell's palsy, however, may be a polyneuropathy, so it is not clear that
      the poor word recognition performance at high levels is necessarily attributable
      specifically to impaired facial nerve function. The present article reports two
      new experiments that probe whether an isolated impairment of the stapedius reflex
      can produce rollover in word recognition performance-intensity functions. In
      experiment 1, performance-intensity functions for monosyllabic speech materials
      were obtained from ten normal listeners under two listening conditions: normal
      and low-frequency augmented to offset the effects of the stapedius reflex on the
      transmission of low-frequency vibrations to the cochlea. There was no effect of
      the spectral augmentation on word recognition for stimulus levels up to 107 dB
      SPL. In experiment 2, six patients who had undergone stapedectomy were tested for
      rollover using performance-intensity functions. None of the patients showed
      rollover in their performance-intensity functions, even at stimulus levels in
      excess of 100 dB HL. These data suggest that if the stapedius reflex has a role
      in protection from upward spread of masking, then this role is inconsequential
      for word recognition in quiet.

PMID- 12051440
TI  - Cooperative interaction as the physical basis of the negative stiffness in hair
      cell stereocilia.
AB  - A recent report confirmed that stiffness of the stereocilia can be negative, as
      predicted by the Howard-Hudspeth model. According to this model, the
      mechanotransducer channel's gating not only reduces the stereociliary stiffness,
      but can alter its sign as well. The basic assumptions of this model do not
      include cooperativity in channel gating. Here we consider two possible
      explanations for the observed negative stiffness. If the stereocilia have a
      special structure so that microscopic displacement can be imposed on each channel
      by controlling the bending of the bundle, negative stiffness can occur without
      channel cooperativity. If such a microscopic condition cannot be imposed by a
      macroscopic manipulation, an additional physical process, such as cooperativity
      in channel gating, is required to explain negative stiffness.

PMID- 12051441
TI  - Responses to cochlear normalized speech stimuli in the auditory nerve of cat.
AB  - Previous studies of auditory-nerve fiber (ANF) representation of vowels in cats
      and rodents (chinchillas and guinea pigs) have shown that, at amplitudes typical
      for conversational speech (60-70 dB), neuronal firing rate as a function of
      characteristic frequency alone provides a poor representation of spectral
      prominences (e.g., formants) of speech sounds. However, ANF rate representations
      may not be as inadequate as they appear. Here, it is investigated whether some of
      this apparent inadequacy owes to the mismatch between animal and human cochlear
      characteristics. For all animal models tested in earlier studies, the basilar
      membrane is shorter and encompasses a broader range of frequencies than that of
      humans. In this study, a customized speech synthesizer was used to create a
      rendition of the vowel [E] with formant spacing and bandwidths that fit the cat
      cochlea in proportion to the human cochlea. In these vowels, the spectral
      envelope is matched to cochlear distance rather than to frequency. Recordings of
      responses to this cochlear normalized [E] in auditory-nerve fibers of cats
      demonstrate that rate-based encoding of vowel sounds is capable of distinguishing
      spectral prominences even at 70-80-dB SPL. When cochlear dimensions are taken
      into account, rate encoding in ANF appears more informative than was previously
      believed.

PMID- 12051442
TI  - Listener weighting of cues for lateral angle: the duplex theory of sound
      localization revisited.
AB  - The virtual auditory space technique was used to quantify the relative strengths
      of interaural time difference (ITD), interaural level difference (ILD), and
      spectral cues in determining the perceived lateral angle of wideband, low-pass,
      and high-pass noise bursts. Listeners reported the apparent locations of virtual
      targets that were presented over headphones and filtered with listeners' own
      directional transfer functions. The stimuli were manipulated by delaying or
      attenuating the signal to one ear (by up to 600 micros or 20 dB) or by altering
      the spectral cues at one or both ears. Listener weighting of the manipulated cues
      was determined by examining the resulting localization response biases. In
      accordance with the Duplex Theory defined for pure-tones, listeners gave high
      weight to ITD and low weight to ILD for low-pass stimuli, and high weight to ILD
      for high-pass stimuli. Most (but not all) listeners gave low weight to ITD for
      high-pass stimuli. This weight could be increased by amplitude-modulating the
      stimuli or reduced by lengthening stimulus onsets. For wideband stimuli, the ITD
      weight was greater than or equal to that given to ILD. Manipulations of monaural
      spectral cues and the interaural level spectrum had little influence on lateral
      angle judgements.

PMID- 12051443
TI  - Effect of delayed auditory feedback on normal speakers at two speech rates.
AB  - This study investigated the effect of short and long auditory feedback delays at
      two speech rates with normal speakers. Seventeen participants spoke under delayed
      auditory feedback (DAF) at 0, 25, 50, and 200 ms at normal and fast rates of
      speech. Significantly two to three times more dysfluencies were displayed at 200
      ms (p<0.05) relative to no delay or the shorter delays. There were significantly
      more dysfluencies observed at the fast rate of speech (p = 0.028). These findings
      implicate the peripheral feedback system(s) of fluent speakers for the disruptive
      effects of DAF on normal speech production at long auditory feedback delays.
      Considering the contrast in fluency/dysfluency exhibited between normal speakers
      and those who stutter at short and long delays, it appears that speech disruption
      of normal speakers under DAF is a poor analog of stuttering.

PMID- 12051444
TI  - Children's use of semantic cues in degraded listening environments.
AB  - Children 5 and 9 years of age and adults were required to identify the final
      words of low- and high-context sentences in background noise. Age-related
      differences in the audibility of speech signals were minimized by selecting
      signal-to-noise ratios (SNRs) that yielded 78% correct performance for low
      context sentences. As expected, children required more favorable SNRs than adults
      to achieve comparable levels of performance. A more difficult listening condition
      was generated by adding 2 dB of noise. In general, 5-year-olds performed more
      poorly than did 9-year-olds and adults. Listeners of all ages, however, showed
      comparable gains from context in both levels of noise, indicating that noise does
      not impede children's use of contextual cues.

PMID- 12051445
TI  - The perception of Cantonese lexical tones by early-deafened cochlear implantees.
AB  - This study investigated whether cochlear implant users can identify Cantonese
      lexical tones, which differ primarily in their F0 pattern. Seventeen early
      deafened deaf children (age= 4 years, 6 months to 8 years, 11 months;
      postoperative period= 11-41 months) took part in the study. Sixteen children were
      fitted with the Nucleus 24 cochlear implant system; one child was fitted with a
      Nucleus 22 implant. Participants completed a 2AFC picture identification task in
      which they identified one of the six contrastive Cantonese tones produced on the
      monosyllabic target word /ji/. Each target stimulus represented a concrete object
      and was presented within a carrier phrase in sentence-medial position. Group
      performance was significantly above chance for three contrasts. However, the
      cochlear implant listeners performed much worse than a 6 1/2-year-old, moderately
      hearing impaired control listener who was tested on the same task. These findings
      suggest that this group of cochlear implant users had great difficulty in
      extracting the pitch information needed to accurately identify Cantonese lexical
      tones.

PMID- 12051446
TI  - Representations of sound that are insensitive to spectral filtering and
      parametrization procedures.
AB  - This paper describes representations of time-dependent signals that are invariant
      under any invertible signal distortion. Such a representation can be created by
      rescaling the signal in a nonlinear dynamic manner that is determined by recently
      encountered signal levels. Information that is encoded in such representations
      will be faithfully communicated in the presence of severe signal distortions,
      which may originate in the transmitter, receiver, or the channel between them. As
      in speech communication, the receiver is "blind" and need not characterize the
      form of the signal distortion, which remains unknown. The method is applied to
      analytical examples, acoustic waveforms of human speech, and the short-term
      Fourier spectra of a bird song. The results suggest that the rescaled
      representation of a sound is insensitive to the way its spectra have been
      filtered and parametrized, as long as those processes do not obliterate the
      differences between the various spectra in the sound. Finally, the possible
      "speaker" independence of these representations is explored in the context of a
      simple linear prediction model of vocal tracts with a single degree of freedom.

PMID- 12051447
TI  - A reflex resonance model of vocal vibrato.
AB  - A reflex mechanism with a long latency (>40 ms) is implicated as a plausible
      cause of vocal vibrato. At least one pair of agonist-antagonist muscles that can
      change vocal-fold length is needed, such as the cricothyroid muscle paired with
      the thyroarytenoid muscle, or the cricothyroid muscle paired with the lateral
      cricoarytenoid muscle or a strap muscle. Such an agonist-antagonist muscle pair
      can produce negative feedback instability in vocal-fold length with this long
      reflex latency, producing oscillations on the order of 5-7 Hz. It is shown that
      singers appear to increase the gain in the reflex loop to cultivate the vibrato,
      which grows out of a spectrum of 0-15-Hz physiologic tremors in raw form.

PMID- 12051448
TI  - Coupled modes of the resonance box of the guitar.
AB  - Vibrations of the resonance box of the guitar have been studied by means of the
      modal analysis technique and the finite-element method. An expert craftsman
      constructed the guitar box with all the structures, internal and external,
      characteristic of a real instrument for the experimental measurements. The
      boundary conditions were chosen in order to clarify the soundboard-back
      interaction only via the internal air coupling. The numerical model allows one to
      study the influence of each component on the whole box, and the contribution of
      the modes of the components (wooden box and its parts, and air), to the coupled
      modes by calculating their participation factors. The coupled modes of the guitar
      box are discussed taking into account both the finite-element and modal analysis
      results.

PMID- 12051449
TI  - Efficiency, accuracy, and stability issues in discrete-time simulations of single
      reed wind instruments.
AB  - A quantitative study of discrete-time simulations for a single reed physical
      model is presented. It is shown that when the continuous-time model is
      discretized, a delay-free path is generated in the computation. A general
      solution is proposed to this problem, that amounts to operating a geometrical
      transformation on the equations. The transformed equations are discretized using
      four different numerical methods. Stability properties of each method are
      assessed through analysis in the frequency domain. By comparing the discrete and
      continuous frequency responses, it is studied how the physical parameters are
      mapped by each method into the discrete-time domain. Time-domain simulations are
      developed by coupling the four digital reeds to an idealized bore model,
      Quantitative analysis of the simulations shows that the discrete-time systems
      produced by the four methods have significantly different behaviors, even when
      high sampling rates are used. As a result of this study, a general scheme for
      accurate and efficient time-domain simulations of the single reed model is
      proposed.

PMID- 12051450
TI  - Acoustic competition in the gulf toadfish Opsanus beta: acoustic tagging.
AB  - Nesting male gulf toadfish Opsanus beta produce a boatwhistle advertisement call
      used in male-male competition and to attract females and an agonistic grunt call.
      The grunt is a short-duration pulsatile call, and the boatwhistle is a complex
      call typically consisting of zero to three introductory grunts, a long tonal boop
      note, and zero to three shorter boops. The beginning of the boop note is also
      gruntlike. Anomalous boatwhistles contain a short-duration grunt embedded in the
      tonal portion of the boop or between an introductory grunt and the boop. Embedded
      grunts have sound-pressure levels and frequency spectra that correspond with
      those of recognized neighbors, suggesting that one fish is grunting during
      another's call, a phenomenon here termed acoustic tagging. Snaps of nearby pistol
      shrimp may also be tagged, and chains of tags involving more than two fish occur.
      The stimulus to tag is a relatively intense sound with a rapid rise time, and
      tags are generally produced within 100 ms of a trigger stimulus. Time between the
      trigger and the tag decreases with increased trigger amplitude. Tagging is
      distinct from increased calling in response to natural calls or stimulatory
      playbacks since calls rarely overlap other calls or playbacks. Tagging is not
      generally reciprocal between fish, suggesting parallels to dominance displays.

PMID- 12051451
TI  - Frequency-dependent attenuation-compensation functions for ultrasonic signals
      backscattered from random media.
AB  - Estimations of scattering parameters, such as average scatterer diameter, from rf
      signals backscattered from random media (tissues) are made from the frequency
      dependence of the rf signal. The frequency dependence of the rf signal
      backscattered from the medium is seen in the normalized power spectrum. The
      normalized power spectrum is found by taking the squared magnitude of the Fourier
      transform of the rf signal gated over a region of interest and dividing by some
      reference spectrum. If the medium has a frequency-dependent attenuation then the
      shape of the normalized power spectrum will be affected by the frequency
      dependent attenuation and the time duration of the gated signal. Not accounting
      for the frequency-dependent attenuation leads to poor estimations of scatterer
      parameters. Larger attenuation and longer time gates give poorer estimates of
      scatterer parameters without attenuation compensation. Several attenuation
      compensation functions have been used to account for the attenuation losses to
      the normalized power spectrum. A new attenuation-compensation function is
      proposed and compared with the other attenuation-compensation routines. The new
      attenuation-compensation function is shown to give improved estimates over
      previous attenuation-compensation functions for scatterers that follow a Gaussian
      form factor.

PMID- 12051452
TI  - Diagnosis of thyroid metastasis in cancer patients with thyroid mass by fine
      needle aspiration cytology and ultrasonography.
AB  - BACKGROUND: Thyroid metastasis is generally thought to be infrequent. To evaluate
      its occurrence, fine needle aspiration cytology and ultrasound of the thyroid
      gland were performed in nonthyroid cancer patients with thyroid mass. METHODS: A
      total of 20 nonthyroid cancer patients (6 males and 14 females with a mean age of
      55 +/- 7 years) with thyroid mass were examined with thyroid ultrasound and fine
      needle aspiration cytology. Their underlying malignancies included lung cancer in
      10 patients, breast cancer in 7 patients, cervical cancer in 2 patients and colon
      cancer in 1 patient. RESULTS: Thyroid metastases were diagnosed in 4 patients
      (20%), 2 with breast cancer and 2 with lung cancer. For 3 of them, thyroid
      ultrasound showed solitary hypoechoic nodule, and in 1 case, multiple nodular
      lesions were demonstrated in each lobe. In addition, neck lymph nodes were noted
      in 3 patients. In the remaining 16 cancer patients, thyroid ultrasound showed
      either multiple or solitary nodular goiter change with no neck lymph node
      involvement. Fine needle aspiration cytology (FNAC) yielded nonthyroid
      adenocarcinoma in 4 metastatic cases. The 2 breast cancer patients received
      finally total thyroidectomy and were still alive 1 year after operation. While in
      the other 2 lung cancer cases, only supportive treatment were given due to
      advanced stages and the patients died within months. CONCLUSIONS: Thyroid
      metastases could occur at a high frequency in nonthyroid cancer patients with
      thyroid mass from our small series. By combining FNAC with ultrasound, a clinical
      diagnosis of thyroid metastasis is attainable in cancer patients with thyroid
      mass.

PMID- 12051453
TI  - Acute pulmonary thromboembolism and occult cancer.
AB  - BACKGROUND: Pulmonary thromboembolism (PTE) is an uncommon disease in Asian
      population when compared with western countries. The definite answer to such a
      rarity remains unclear. The association of occult malignancy with acute PTE has
      been well documented in western countries, but has not been reported in Asia. The
      purpose of this study is to evaluate the occurrence of malignancy after the
      episode of acute PTE in Chinese patients. METHODS: We retrospectively analyzed
      the patients with acute PTE by chart review (ICD-9:415.9) in Taipei Veterans
      General Hospital from July, 1993 to June, 1998. Patients were clinically followed
      in out-patient clinic for at least 12 months. RESULTS: A total of 45 patients
      with acute PTE were identified under strict diagnostic criteria. In the follow-up
      period, 9 patients with cancer were identified. After exclusion of the cases
      without regular follow-up and those who died on the acute phase of PTE, the
      adjusted cancer occurrence after or concomitant with acute PTE in our study was
      47.37%, which was significantly higher than previous reports. The origins of
      malignancy were mainly gastrointestinal tract and genitourinary system, similar
      to the reports from western countries. CONCLUSIONS: The prevalence of occult
      malignancy after acute PTE is high among Chinese patients in Taiwan. Physicians
      should be aware of this association, and cancer survey should be performed after
      the patients are stabilized from acute PTE.

PMID- 12051454
TI  - Benign diffuse islet cell disease in adults: a comparison of the results from
      distal and arterial stimulated venous sampling-guided pancreatectomies.
AB  - BACKGROUND: Adequate surgical treatment of hypoglycemia caused by benign diffuse
      islet cell disease (BDICD) is not associated with predictable results. Arterial
      stimulation and venous sampling (ASVS) has been reported to establish the
      diagnosis of BDICD, as well as serve as a guide to resection. The purpose of this
      study is to determine the efficacy of this method for the treatment of benign
      diffuse islet cell disease. METHODS: We retrospectively reviewed 38 adults with
      symptomatic hyperinsulinemic hypoglycemia treated by a single surgeon from 1982
      to 1998. Nine of them had pathologic evidence of BDICD. We demonstrated the
      clinical presentations, serum level of fasting blood sugar, insulin and C-peptide
      before and after operations, pathological results, and outcomes of distal
      pancreatectomy in 5 patients and ASVS-guided pancreatectomies in 4 patients with
      BDICD. RESULTS: Five patients (4 females and 1 male) who received distal
      pancreatectomy (Group 1) were aged from 19 to 75, and were culled from a group of
      30 patients with spontaneous hyperinsulinemic hypoglycemia. Two had the multiple
      endocrine neoplasia (MEN) 1 syndrome. The follow-up was from 7 to 16 years. Three
      patients (including 1 MEN 1 patient) became diabetic. Another 1 is euglycemic,
      and the other MEN 1 patient developed recurrent disease. Four patients (2 males
      and 2 females, Group 2), found in a group of 8 patients with hyperinsulinemic
      hypoglycemia, had ASVS-guided pancreatectomies. Their ages ranged from 29 to 69
      years. The area of the pancreas supplied by the splenic artery was removed in all
      patients. Follow-up from half to 2 years showed that all the patients had normal
      fasting levels of glucose, normal levels of insulin and C-peptide, and no more
      hypoglycemic attacks. CONCLUSIONS: Arterial stimulation venous sampling is a
      useful guide for pancreatectomy to treat adult patients with BDICD. Data from
      this small sample of patients suggest that the results may be superior to those
      obtained by "blind" distal pancreatectomy.

PMID- 12051455
TI  - Epstein-Barr virus and lymphoid hematological disorders.
AB  - BACKGROUND: To study the role of Epstein-Barr virus (EBV) in the carcinogenesis
      of various lymphoid neoplasms in Taiwan, a nonisotopic in situ hybridization
      (ISH) technique was used to detect the expression of EBV-encoded small RNAs
      (EBERs) in various lymphoid neoplasms. METHODS: We obtained the paraffin-embedded
      tissues of various hematological malignancies from the Department of Pathology,
      Tri-Service General Hospital. Nonisotopic ISH technique was employed to detect
      EBERs and immunohistochemical staining was performed to confirm the cell lineage.
      RESULTS: Our data showed the frequency of EBV infection on various lymphoid
      malignancies as followed: Burkitt's lymphoma (BL) (10/18); non-Burkitt's Non
      Hodgkin's lymphoma (3/42); non-Hodgkin's lymphoma, T cell type, nasal (NHLTN)
      (5/5); Hodgkin's disease (2/9); acute lymphocytic leukemia (1/24); chronic
      lymphocytic leukemia (1/15); and multiple myeloma (2/18). In the control group,
      none of the specimens from patients of acute myelocytic leukemia and
      myelodysplastic syndrome was positive for EBERs. CONCLUSIONS: Among the various
      lymphoid neoplasms we studied, only BL (p < 0.05) and NHLTN (p < 0.05) were found
      to have an association with EBV statistically.

PMID- 12051456
TI  - Multiple epidermoid cysts arising in a cryptorchid testis following ochiopexy.
AB  - Epidermoid cysts of the testis are rare benign intratesticular lesions,
      representing about 1-2% of all intratesticular tumors. In the English literature,
      the total reported number of patients with an epidermoid cyst is approximately
      300. Almost all of the previous reports were of a single lesion in a testis and
      the occurrence of epidermoid cysts in cryptorchid testis was extremely rare.
      Herein, we report on a patient with multiple epidermoid cysts in a cryptorchid
      testis following orchiopexy. Because the cysts arose in a cryptorchid testis and
      occupied most of the space of the testis, orchiectomy was performed.

PMID- 12051457
TI  - Endoscopic management of a ureterocele in complete ureteric duplication of an
      infant.
AB  - A 2-month-old female infant with an initial symptomatic presentation of fever
      suffered from persistent febrile urinary tract infections and was treated with
      antibiotics. Further evaluation including voiding cystourethrography (VCUG), Tc
      99m dimercaptosuccinic acid (DMSA) scan, intravenous urography (IVU) showed a
      ureterocele and hydroureteronephrosis in the upper moiety of a left duplicated
      kidney. Endoscopic incision of the ureterocele was successful in treating the
      ureterocele, urinary tract infection and salvaging the function of the upper
      moiety of the kidney in a 1-year follow-up visit.

PMID- 12051458
TI  - In utero sonographic findings in a fetus with a hereditary multiple intestinal
      atresia.
AB  - Hereditary multiple intestinal atresia is a rare syndrome with an autosomal
      recessive pattern of inheritance. We described the antenatal sonographic
      appearance of a case of hereditary multiple intestinal atresia. A markedly
      dilated cystic mass noncommunicating with the stomach was observed in the right
      upper quadrant of the fetal abdomen by an ultrasound scan at 30 weeks of
      gestation. Real-time sonographic evidence of strong peristaltic activity was not
      demonstrated. The infant weighing 2315 g was delivered at 35 week's gestation
      with Apgar scores of 7 and 9 at 1 and 5 minutes, respectively. At laparotomy, a
      prepyloric septal atresia, multiple-level small intestinal atresias and a rectal
      diaphragm were discovered. The infant died 52 days after the operation. The
      sonographer should be aware that a proximal bowel distention can be associated
      with hereditary multiple intestinal atresia in patients with a family history of
      an affected sibling.

PMID- 12051459
TI  - Diffuse pancreatic islet cell disease with hyperinsulinism in adults: problems in
      recognition and management.

PMID- 12051460
TI  - Modified quantitative detection of apoptosis in coronary atherosclerosis.
AB  - BACKGROUND: Apoptosis, or programmed cell death, is a physiological cell death
      process that allows a tissue or organ to remove unwanted cells and responsible
      for the maintenance of stable cell numbers in tissues even in primary
      atherosclerotic or restenotic lesion of coronary artery. Previous studies on the
      apoptosis of coronary atherosclerosis are usually prone to run into qualitative
      description without the aid of "quantitative" evaluation. To eliminate such
      subjective errors, we have designed a triple immunofluorescent stain assessed by
      digital camera and computer-aided analysis system so that the actual quantitative
      apoptotic expression of coronary atherosclerotic development can be more
      precisely evaluated. METHODS: Specimens of coronary artery were obtained from
      consecutive patients undergoing coronary endarterectomy or cardiac
      transplantation. Twenty-seven blocks of paraffin tissue specimens from 16
      patients were analyzed. According to the American Heart Association (AHA)
      classification of atherosclerotic lesion, type I, II, III lesions were defined as
      early lesions and the other three types: IV, V, and VI as advanced lesions.
      Apoptosis and cell types were recognized simultaneously by triple
      immunofluorescent stain combined with Hoechst, Terminal deoxynucleotidyl
      transferase-mediated dUTP Nick End-Labeling (TUNEL) and smooth muscle cell (SMC)
      marker staining. Apoptotic index deduced from TUNEL-positive nucleus number
      divided by Hoechst-positive nucleus number. Apoptotic cell-type index deduced
      from TUNEL-positive nuclei, which are surrounded by cell type fluorescent marker,
      divided by total TUNEL-positive nuclei. RESULTS: Fourteen early lesions and 13
      advanced lesions of tissue specimens were analyzed in this study. The mean
      apoptotic index of early lesions was 2.60 +/- 1.72%, which is significantly lower
      than that of the advanced lesions (7.42 +/- 3.07%). The apoptosis between the
      tapering portion and lesion portion obtained from 10 coronary endarterectomy
      specimens was also significantly different (2.59 +/- 1.90% vs 8.10 +/- 3.20%). In
      either early or advanced lesions, the predominant cell type of apoptosis was SMC.
      CONCLUSIONS: The identical counting and quantification analytic method we
      designed is more accurate and quantitative than the traditional investigation in
      detecting and affirming the "homeostasis" role of apoptosis in the
      atherosclerotic pathogenesis process of coronary artery disease.

PMID- 12051461
TI  - Disability and treatment patterns of multiple sclerosis patients in United
      States: a comparison of veterans and nonveterans.
AB  - The Veterans Health Administration (VHA) is the largest integrated healthcare
      system in the world and provides care to approximately 20,000 multiple sclerosis
      (MS) patients. Here, we report that these MS patients are disproportionately more
      likely to be older, male, unemployed, and disabled with lower levels of education
      and financial resources when compared to veterans not receiving care within the
      VHA or to nonveteran MS patients. When comparing the VHA MS patients to a cohort
      of nonveteran MS patients matched for age, sex, and disability, we found that
      veterans receiving care within the VHA were equally likely to have received care
      from a neurologist and more likely to have received care from rehabilitation
      specialists and primary care physicians than nonveterans. Similarly, veterans in
      the VHA were more likely to receive therapy with certain symptomatic medications
      but were less likely to be treated with disease-modifying agents for MS (DMAMS)
      than nonveterans. When treated with DMAMS, they are more likely to be treated
      with Avonex and significantly less likely to receive treatment with Copaxone or
      Novantrone.

PMID- 12051462
TI  - Epidemiology and current treatment of multiple sclerosis in Europe today.
AB  - Multiple sclerosis (MS) is a chronic disease affecting the central nervous
      system, usually leading to early disablement in young adults. At least 350,000
      persons in Europe have the disease. Wide variations exist both between and within
      European countries in the incidence and prevalence of the disease as well as in
      the general standard of care for MS patients. The needs, well-being, and social
      participation of people with MS are systematically influenced by their physical
      and cultural environment and the nature of the community services. Moreover, the
      rate of introduction of the new disease-modifying therapy also widely differs
      from country to country. This article helps clinical researchers to understand
      better the differences in epidemiology and in the current treatment of MS in
      Europe.

PMID- 12051463
TI  - The immunopathogenesis of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a T cell-mediated autoimmune disease that is triggered
      by unknown exogenous agents in subjects with a specific genetic background. Genes
      of the major histocompatibility complex class II region are the only ones that
      have been consistently associated with the disease. However, susceptibility is
      probably mediated by a heterogeneous array of genes, which demonstrate epistatic
      interactions. Furthermore, an infectious etiology of MS has been suggested, and
      it is likely that infectious agents shape the immune response against self
      antigens. Composition of plaques, response to therapy, and data from animal
      models indicate that MS is mediated by myelin-specific CD4 T cells that, upon
      activation, invade the central nervous system and initiate the disease. Different
      patterns of tissue damage have been shown in active MS lesions, suggesting that
      the mechanisms of injury are probably distinct in different subgroups of
      patients. Heterogeneity in clinical characteristics, magnetic resonance imaging,
      and response to therapies support this notion. The experience gained during
      several pharmacological studies has improved our understanding of the
      pathogenesis of MS. New tools, such as gene expression profiling with cDNA
      microarrays and proteomics, together with advancements in imaging techniques may
      help us to identify susceptibility genes and disease markers, which may enable us
      to design more effective therapies and to tailor them according to different
      disease forms or stages.

PMID- 12051464
TI  - New insights into the genetics of multiple sclerosis.
AB  - Tissue injury in multiple sclerosis (MS) results from an abnormal immune response
      to one or more myelin antigens that develop in genetically susceptible
      individuals after exposure to a causal agent that is yet undefined. The genetic
      component of MS etiology is believed to result from the action of several genes
      of moderate effect. The incomplete penetrance of MS susceptibility alleles
      probably reflects interactions with other genes, posttranscriptional regulatory
      mechanisms, and significant environmental influences. Equally significant is that
      genetic heterogeneity also likely exists, meaning that specific genes influence
      susceptibility and pathogenesis in some affecteds but not in others. Some loci
      may be involved in the initial pathogenic events, while others could influence
      the development and progression of the disease. The past few years have seen
      significant progress in the developments of laboratory and analytical approaches
      to study non-Mendelian complex genetic disorders and to define the pathological
      basis of demyelination. These developments have set the stage for the final
      characterization of the genes involved in MS susceptibility and pathogenesis. The
      identification and characterization of the genes are likely to define the basic
      etiology of the disease, improve risk assessment, and influence therapeutics.

PMID- 12051465
TI  - Fatigue in multiple sclerosis: current understanding and future directions.
AB  - Fatigue is a very common symptom of multiple sclerosis (MS). Theoretically,
      fatigue may be related to neuromodulation by soluble products of the autoimmune
      process or by disruption of central nervous system pathways necessary for
      sustained activity, but little empirical evidence supports these possibilities.
      Amantadine, pemoline, and modafanil improved fatigue in placebo-controlled
      clinical trials, but these studies all had significant limitations. Difficulty
      measuring fatigue has impeded studies of its characteristics, mechanisms, and
      therapeutics. Most studies have relied on self-report questionnaires. These may
      be inappropriate, however, because they can be easily confounded by other
      symptoms of MS, they are entirely subjective, and they require patients to make
      difficult retrospective assessments. Studies of fatigue would be improved by
      including measures of more rigorously defined, quantifiable components of
      fatigue. For example, motor fatigue can be measured as the decline in strength
      during sustained muscle contractions. Cognitive fatigue can be measured as the
      analogous decline in cognitive performance during tasks requiring sustained
      attention. Lassitude is defined as a subjective sense of reduced energy, and it
      can be measured with the use of a visual analog diary. These measures provide
      reproducible results and demonstrate significant differences between MS patients
      and healthy controls. Dividing fatigue into these components can provide
      objective assessments that are less likely to be confounded by other symptoms of
      MS, such as weakness, spasticity, cognitive impairment, and depressed mood.

PMID- 12051466
TI  - Pain in multiple sclerosis: a biopsychosocial perspective.
AB  - Clinically significant pain has been found in as many as 65% of persons diagnosed
      with multiple sclerosis (MS). Acute pain conditions include trigeminal neuralgia,
      painful optic neuritis, and Lhermitte's syndrome. Chronic pain conditions such as
      dysesthesias in the limbs, joint pain, and other musculoskeletal or mechanical
      pain problems develop as a function of spasticity and deconditioning associated
      with MS. These painful conditions may respond to pharmacological, surgical,
      rehabilitation, and psychological interventions. However, unresolved pain,
      associated disability, and affective distress are common. In addition, efforts to
      manage MS and its associated symptoms, for example, may inadvertently cause
      osteoporosis and headache or other symptoms that may exacerbate pain and pain
      related disability. Conversely, efforts to manage pain may have negative effects
      on the symptoms of MS (e.g., increased fatigue). A multidimensional approach to
      assessment and management that is guided by a comprehensive biopsychosocial model
      is recommended. Such an approach needs to consider the exacerbating nature of MS,
      MS-related pain, and interventions aimed at their management. Suggestions for
      future research on MS-related pain conclude the article.

PMID- 12051467
TI  - Sodium channels as molecular targets in multiple sclerosis.
AB  - Sodium channels are expressed at high density in myelinated axons and play an
      obligatory role in conducting action potentials along axons within the mammalian
      brain and spinal cord. It is not surprising, therefore, that they are involved in
      several aspects of the pathophysiology of multiple sclerosis (MS). First, the
      deployment of additional sodium channels to demyelinated parts of the axon (which
      had expressed low densities of sodium channels when covered by the myelin)
      provides a molecular substrate for the restoration of action potential
      conduction, a process that contributes to remissions in patients with MS. Second,
      there is evidence for changes in the expression pattern of sodium channels within
      Purkinje cells, both in animal models of MS and in human MS. It has been
      hypothesized that dysregulated sodium channel expression may contribute to
      symptom production in MS. If this hypothesis is correct, subtype-specific channel
      blockade may be therapeutically effective as a symptomatic treatment for ataxia
      and other cerebellar symptoms in MS. Finally, a noninactivating sodium
      conductance can trigger calcium-mediated axonal injury via reverse sodium-calcium
      exchange. Identifying the underlying channel may permit the development of
      therapeutic strategies that will prevent or retard axonal degeneration in MS.

PMID- 12051468
TI  - MR-based technology for in vivo detection, characterization, and quantification
      of pathology of relapsing-remitting multiple sclerosis.
AB  - In relapsing-remitting (RR) multiple sclerosis (MS), conventional magnetic
      resonance (MR) imaging (MRI) has proved to be a valuable tool to assess the
      lesion burden and activity over time. However, conventional MRI cannot
      characterize and quantify the tissue damage within and outside such lesions and
      only can provide some gross measures reflecting the presence of irreversible
      tissue damage, such as the load of T1 "black holes" and the severity of brain or
      cord atrophy. Other MR-based techniques, including cell-specific imaging,
      magnetization transfer (MT) MRI (MT-MRI), diffusion-weighted (DW) MRI (DW-MRI),
      proton magnetic resonance spectroscopy (1H-MRS), and functional MRI (fMRI), have
      the potential to overcome this limitation and, consequently, to provide
      additional information about the nature and the extent of MS tissue damage, which
      would inevitably remain undetected when only a conventional MRI is obtained. Cell
      specific imaging should result in a better definition of the cellular mechanisms
      associated with MS inflammation. Metrics derived from MT- and DW-MRI can quantify
      the structural changes occurring within and outside lesions visible on
      conventional MRI scans. 1H-MRS could add information on the biochemical nature of
      such changes. fMRI is a promising technique to assess the mechanisms of cortical
      reorganization, which may limit the consequences of an MS-related injury. The
      application of these MR techniques to the study of RRMS is likely to provide
      useful insights into the pathophysiology of this disease and to improve our
      ability to assess the efficacy of experimental treatments.

PMID- 12051470
TI  - Immunotherapy of multiple sclerosis--current practice and future directions.
AB  - Over the past decade, multiple sclerosis (MS) has become a treatable neurological
      disease. This paper reviews the therapies that have been studied to treat MS and
      discusses various treatment approaches on the horizon. Immunosuppressive and
      immunomodulatory therapies have been shown to alter the long-term course of MS.
      Therapies are currently available for relapsing-remitting, secondary progressive,
      and progressive relapsing disease. Although effective, these therapies have a
      modest impact on reduction in relapse rate and slowing of disease progression.
      Much work is needed to improve upon this modest effect and hopefully obtain a
      cure.

PMID- 12051469
TI  - Magnetic resonance imaging in primary progressive multiple sclerosis.
AB  - Ten to fifteen percent of patients with multiple sclerosis (MS) have a condition
      that is progressive from onset without a preceding relapsing-remitting phase:
      this is known as primary progressive multiple sclerosis (PPMS). Patients with
      PPMS tend to be older, often present with motor symptoms and, in contrast to
      relapsing MS, are as likely to be male as female. The conventional magnetic
      resonance imaging (MRI) characteristics of PPMS include a tendency to lower
      lesion loads and lower rate of new lesion formation. In common with relapsing MS,
      the relation between conventional MRI abnormalities and clinical condition is
      poor. Studies using newer MRI techniques, such as magnetization transfer imaging
      (MTI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy (MRS),
      and functional MRI (fMRI), have also been carried out. These techniques are
      sensitive to a wider range of abnormalities within tissue, and their increased
      pathological specificity may be helpful in clarifying the underlying pathology of
      the condition.

PMID- 12051471
TI  - Cell transplantation of peripheral-myelin-forming cells to repair the injured
      spinal cord.
AB  - Much excitement has been generated by recent work showing that a variety of
      myelin-forming cell types can elicit remyelination and facilitate axonal
      regeneration in animal models of demyelination and axonal transection. These
      cells include peripheral-myelin-forming cells, such as Schwann cells and
      olfactory ensheathing cells. In addition, progenitor cells derived from the
      subventricular zone of the brain and from bone marrow (BM) can form myelin when
      transplanted into demyelinated lesions in rodents. Here, we discuss recent
      findings that examine the remyelination potential of transplantation of
      peripheral-myelin-forming cells and progenitor cells derived from brain and bone
      marrow. Better understanding of the repair potential of these cells in animal
      models may offer exciting opportunities to develop cells that may be used in
      future clinical studies.

PMID- 12051472
TI  - An overview of assistive technology for persons with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a progressive neurologic disease clinically
      characterized by episodes of focal disorder of the cranial nerves, spinal cord,
      and the brain. MS affects a significant number of young adults, and they most
      often face a future of progressive functional losses as more of their central
      nervous system and cranial nerves are affected. As the disease progresses, they
      have new impairments with accompanying limitations in activities, restrictions to
      their participation in life, and compromised quality of life. Assistive
      technology includes any item that is used to maintain or improve functional
      capabilities. The rehabilitation healthcare provider has many opportunities to
      intervene with assistive technologies to decrease activity limitations and
      participation restrictions. The purpose of this article is to (1) review the
      impairments and associated activity limitations and participations restrictions
      experienced by persons with MS, (2) provide an overview of high- and low-tech
      assistive technologies appropriate for persons with MS, (3) discuss funding
      opportunities for assistive technologies, (4) review current studies of assistive
      technology used for persons with MS and discuss future research directions, and
      (5) consider assistive technology as an intervention for disability prevention.

PMID- 12051473
TI  - Multiple sclerosis: paradox and public policy.

PMID- 12051474
TI  - Development and validation of a tertiary simulation model for predicting the
      potential growth of Salmonella typhimurium on cooked chicken.
AB  - The growth of Salmonella typhimurium (ATCC 14028) on the surface of autoclaved
      ground chicken breast and thigh burgers incubated at constant temperatures from 8
      to 48 degrees C in 2 degrees C increments was investigated and modeled. Growth
      curves at each temperature were fit to a two-phase linear primary model to
      determine lag time (lambda) and specific growth rate (mu). Growth of S.
      typhimurium on breast and thigh meat was not different. Consequently, secondary
      models that predicted lag time and specific growth rate as a function of
      temperature were developed with the combined data for breast and thigh meat. Five
      secondary models for lag time and three secondary models for specific growth rate
      were compared. A new version of the hyperbola model and a cardinal temperature
      model were selected as the best secondary models for lag time and specific growth
      rate, respectively. The secondary models were combined in a computer spreadsheet
      to create a tertiary simulation model that predicted the potential growth (log10)
      increase) of S. typhimurium on cooked chicken as a function of time and
      temperature. Probability distributions and simulation were used in the tertiary
      model to model the secondary model parameters and the times and temperatures of
      abuse. The outputs of the tertiary model were validated (prediction bias of -4%
      for lambda and 1% for mu and prediction accuracy of 10% for lambda and 8% for mu)
      and integrated with a previously developed risk assessment model for Salmonella.

PMID- 12051475
TI  - Enhanced antimicrobial effects of combination of lactate and diacetate on
      Listeria monocytogenes and Salmonella spp. in beef bologna.
AB  - The antimicrobial activities of salts of organic acids such as lactate and
      acetate are well documented, but there is limited information on their effect
      when used in combination. We previously reported enhanced inhibition of Listeria
      monocvtogenes and Salmonella enterica serovar Enteritidis in sterile comminuted
      beef at 5 and 10 degrees C by combinations of sodium lactate (SL) (2.5%) and
      sodium diacetate (SDA) (0.2%). The present study was undertaken to evaluate the
      inhibitory effect of these salts, alone and in combination, in ready-to-eat (RTE)
      meat. Single strains and six-strain mixtures of each of the pathogens (
      approximately 3 log CFU/g) were tested in beef bologna during aerobic storage at
      5 and 10 degrees C for up to 60 days. The growth rate of the six-strain mixture
      of Listeria was faster than that of the single strain (Scott A) in the
      lactate/diacetate-free product. While each of the salts delayed growth of the
      listeriae at 5 degrees C, the effect of their combination was listericidal for
      the single strain and listeriostatic for the six-strain mixture. Enhanced
      inhibition by the salt combination was also observed at 10 degrees C. Salmonella
      numbers declined to undetectable levels in the untreated meat product and in each
      of the treatments after 20-30 days. However, the decline was more rapid in meat
      with the combination of the salts during storage at both 5 and 10 degrees C. Each
      of the salts further delayed the growth of the background microflora during
      storage at 5 degrees C, with their combinations showing the most effect.

PMID- 12051476
TI  - Sodium chloride decreases the bacteriocidal effect of acid pH on Escherichia coli
      O157:H45.
AB  - To reduce the risk of foodborne illness, many fermented and minimally processed
      foods rely on the "hurdle effect", i.e. a combination of two or more inhibitory
      agents being more inhibitory than any of the agents alone. However, we have
      observed that such a combination of agents is not always more inhibitory to
      foodborne pathogens than one alone. In this paper, we show that a combination of
      NaCl and acid pH is less effective than acid pH alone in reducing the numbers of
      Escherichia coli O157:H45. The presence of sodium chloride reduces the
      bacteriocidal effect of lactic acid on logarithmically growing cells of E. coli
      O157:H45. with approximately 10(3)-fold more survivors at pH(o) 4.2 when 4% NaCl
      was added to the medium. A similar protective effect was also seen with other
      organic acidulants and E. coli strains. The cytoplasmic pH (pH(i)) of cells in
      medium at pH 4.2 containing added salt was 5.8 which was 0.56 units higher than
      that of cells in the same medium without added salt. When the pH(i) of cells in
      medium without added salt was adjusted to the same value (5.8) by adding KOH, the
      rate of survival was also considerably greater than that of cells in medium
      without added salt. These data suggest that E. coli can use NaCl to counteract
      acidification of its cytoplasm by organic acids, and in addition, that
      combinations of antimicrobial agents cannot always be relied upon to achieve
      additive antimicrobial effects.

PMID- 12051477
TI  - Estimating the precision of serial dilutions and viable bacterial counts.
AB  - The propagation of error in serial dilutions was investigated theoretically and
      by means of computer simulations. The principal aim of the study was, given only
      the pipette manufacturer's specification, to estimate the variance of any step in
      a dilution series both of pure solutions and of homogeneous bacterial suspensions
      by means of simple formulae. The study was extended to include bacterial plate
      counts by both the standard and the Miles and Misra methods. It was found that
      such estimation was possible and that the distributions approximated the normal
      sufficiently for the construction of confidence intervals (Cls) by the usual
      method. Such intervals can be regarded as minima which could be inflated by
      other, possibly undetermined, factors. It is suggested that laboratories could
      construct tables such as that reported here for pipettes and methods in common
      use to facilitate estimation. While replication of the final sampling step of a
      plate count increases the precision of estimation, averaging across dilutions may
      decrease precision and is not recommended for the standard pour-plate count.

PMID- 12051478
TI  - Nystatin and osmotica as chemical enhancers of the phenotypic adaptation to
      freeze-thaw stress in Geotrichum candidum ATCC 204307.
AB  - Geotrichum candidum is a yeast-like fungus used as ripening starter in cheese
      making. The present study focused on chemical stress pretreatments affecting
      survival of G. candidum ATCC 204307 to freeze-thaw stress. Cryotolerance of G.
      candidum cells was induced by pretreatment with NaCl, CaCl2, or MgCl2, indicating
      heterologous phenotypic adaptation to freeze-thaw stress (- 20 to 25 degrees C)
      by osmotic stress. Furthermore, the nystatin, an antifungal compound, was shown
      to be a cryotolerance inducer.

PMID- 12051479
TI  - Biochemical characterization of horA-independent hop resistance mechanism in
      Lactobacillus brevis.
AB  - We isolated a strain from hop-resistant Lactobacillus hrevis ABBC45, which had
      lost a plasmid (pRH45) harboring a putative hop resistance gene, horA. The hop
      resistance level of this horA-deficient strain, named ABBC45(C), was initially
      low but gradually induced by repeated growth in media containing progressively
      increasing levels of hop compounds. Although the hop resistance level was
      substantially lower than that of the hop-adapted wild type strain, hop-adapted
      ABBC45(C) (ABBC45(CR)) was still capable of growing in beer, suggesting ABBC45
      possesses at least two hop resistance mechanisms. Hop resistance acquired by
      ABBC45(CR) gradually diminished to the pre-adapted level, when the strain was
      grown repeatedly in the absence of hop compounds. ABBC45(CR) was found to be
      cross-resistant to several structurally unrelated drugs, including ethidium
      bromide, daunomycin and nisin. In addition, ABBC45(CR) was shown to extrude
      ethidium in an energy-dependent manner, while ABBC45(C) did not show such
      activity. This indicates that the efflux pump was induced by adaptation to hop
      compounds. The efflux activity of ethidium was reduced by the addition of hop
      compounds, suggesting hop compounds are also the substrate of the efflux pump. It
      was also shown that the efflux activity was completely dissipated with the
      abolition of proton motive force (PMF). These results, taken together, suggest
      the hop resistance mechanism of ABBC45(C) is mediated by PMF-dependent multidrug
      efflux pump.

PMID- 12051480
TI  - Peptidolytic, esterolytic and amino acid catabolic activities of selected
      bacterial strains from the surface of smear cheese.
AB  - Enzymes produced by bacteria present on the surface of smear cheeses play
      essential roles in flavour development during cheese ripening. In this study,
      strains including brevibacteria, corynebacteria, staphylococci and
      brachybacteria, from the surface of two smear cheese (Tilsit and Gubeen) were
      screened for a range of enzyme activities including aminopeptidase (substrates:
      Leu-pNA and His-pNA), dipeptidase (Met-Ala, Ala-Met, Pro-Ala, His-Leu and Pro
      Leu), tripeptidase (Phe-Gly-Gly, Gly-Gly-Gly and Leu-Ala- Pro), esterase (beta
      naphthyl butyrate, beta-naphthyl caprate and beta-naphthyl palmitate). L
      methionine aminotransferase and cystathionine lyase activities. There were marked
      differences in the activities observed between different bacteria studied.
      Brachybacteria showed low activity on all substrates assayed. There was no
      consistency in activities within groups of related bacteria. For example,
      Staphylococcus equorum 14 showed higher activity than S. equorum 6 on all the
      substrates tested. Among the corynebacteria, Coryebacterium ammoniagenes CA8 had
      greatest aminopeptidase, esterase and cystathionine lyase activity while C. casei
      B showed more di- and tri-peptidase activity. It was noted that individual
      bacteria displayed similar activities on all three esterase substrates, i.e., the
      chain length of the fatty acid did not appear to affect activity. L-Methionine
      aminotransferase activity was observed in only one strain (S. equorm 14) whereas
      all strains had cystathionine lyase activity.

PMID- 12051482
TI  - A cognitive theory of compulsive checking.
AB  - It is proposed that compulsive checking occurs when people who believe that they
      have a special, elevated responsibility for preventing harm, mainly to others,
      are unsure that the perceived threat has been reduced or removed. The intensity
      and duration of this checking is determined by three "multipliers": increased
      responsibility, probability of harm and anticipated seriousness of harm. The
      recurrency of the checking is promoted by a self-perpetuating mechanism,
      comprising four elements: paradoxical increases in responsibility and in
      perceived probability of harm, reduced confidence in memory and the absence of a
      certain end to the threat. The relation between compulsive checking and other
      anxiety disorders is examined and the successes and failures of past or present
      treatments re-considered. Experimental predictions are set out and the
      therapeutic implications of the construal are discussed.

PMID- 12051481
TI  - The role of optimism in the process of schema-focused cognitive therapy of
      personality problems.
AB  - The aim of this study was to examine the determinants and effects of optimism in
      the process of schema-focused cognitive therapy of personality problems. The
      sample consisted of 35 patients with panic disorder and/or agoraphobia and DSM-IV
      Cluster C personality traits who participated in an 11-week residential program
      with one symptom-focused and one personality-focused phase. This study examines
      the role played by optimism during the individual sessions of the second phase,
      using a time series approach. Decreased patient's belief in his/her primary Early
      Maladaptive Schema and increased patient-experienced empathy from the therapist
      in a session predicted increased patient-rated optimism before the subsequent
      session. Increased patient-rated optimism in turn predicted decreased schema
      belief and distress and increased insight, empathy, and therapist-rated optimism.
      The slope of optimism across sessions was related to change in most of the
      overall outcome measures. There appears to be a positive feedback in the process
      of schema-focused cognitive therapy between decreased schema belief and increased
      optimism. In addition, optimism appears to mediate the effects of schema belief
      and therapist empathy on overall improvement, and to serve as an antecedent to
      decreased distress and to increased empathy, insight, and therapist's optimism.

PMID- 12051483
TI  - Intermittent explosive disorder and other psychiatric comorbidity among court
      referred and self-referred aggressive drivers.
AB  - We assessed possible Axis I and Axis II disorders in two groups of aggressive
      drivers (n=20, court-referred; n=10, self-referred) and 30 non-aggressive driver
      controls, using the SCID and SCID-II. Aggressive drivers were more likely than
      controls to be positive for any Axis I and Axis II disorders. They were also more
      likely to meet the criteria for Intermittent Explosive Disorder (IED), current or
      past alcohol or substance abuse or dependence and Antisocial PD and Borderline
      PD. The self-referred aggressive drivers were more likely than court-referred
      aggressive drivers to meet the criteria for a current or past Anxiety Disorder.
      Re-analysis of aggressive driver data on the basis of presence or absence of IED
      revealed differences only in Axis II disorders: those with IED were more likely
      to meet the criteria for any Axis II disorder and Antisocial PD.

PMID- 12051484
TI  - Thought action fusion: can it be corrected?
AB  - The goal of this study was to investigate whether or not a brief educational
      intervention delivered prior to engaging in an anxiety-provoking task (writing a
      sentence about hoping that a friend/relative was in a car accident) would be
      effective in offsetting anxiety in college students with a strong propensity to
      endorse statements of thought action fusion (TAF). As hypothesized, individuals
      receiving the educational intervention were less anxious than a placebo
      intervention control group at post task; they were also less likely to endorse
      statements of TAF after receiving the educational intervention. Also, those who
      chose to neutralize after writing the sentence (regardless of experimental group)
      were more likely to report feeling guiltier, more immoral and a greater sense of
      responsibility about writing the sentence prior to neutralizing than those who
      did not subsequently neutralize. These results are discussed in relation to the
      cognitive theory of obsessive-compulsive disorder and implications for prevention
      programs.

PMID- 12051486
TI  - Patients with generalized social phobia direct their attention away from faces.
AB  - The experiment tested whether patients with social phobia direct their attention
      to or away from faces with a range of emotional expressions. A modified dot probe
      paradigm (J. Abnorm. Psychol. 95 (1986) 15) measured whether participants
      attended more to faces or to household objects. Twenty patients with social
      phobia were faster in identifying the probe when it occurred in the location of
      the household objects, regardless of whether the facial expressions were
      positive, neutral, or negative. In contrast, controls did not exhibit an
      attentional preference. The results are in line with recent theories of social
      phobia that emphasize the role of reduced processing of external social cues in
      maintaining social anxiety.

PMID- 12051485
TI  - Posttraumatic stress disorder after motor vehicle accidents: 3-year follow-up of
      a prospective longitudinal study.
AB  - The paper presents a 3-year follow-up of a prospective longitudinal study of
      posttraumatic stress disorder (PTSD) after motor vehicle accidents (J. Abnormal
      Psychol., 107 (1998) 508). Participants were 546 patients who had been assessed
      when attending an emergency clinic shortly after a motor vehicle accident, and at
      3 months and 1 year afterwards. The prevalence of posttraumatic stress disorder
      PTSD at 3 years was 11%. Maintaining psychological factors, i.e. negative
      interpretation of intrusions, rumination, thought suppression and anger
      cognitions, were important in predicting the persistence of PTSD at 3 years, as
      were persistent health and financial problems after the accident. Other
      predictors were female sex, hospital admission for injuries, perceived threat and
      dissociation during the accident, and litigation.

PMID- 12051487
TI  - Predicting anxious response to a social challenge: the predictive utility of the
      social interaction anxiety scale and the social phobia scale in a college
      population.
AB  - Trait anxiety is believed to be a hierarchical construct composed of several
      lower-order factors (Adv. Behav. Res. Therapy, 15 (1993) 147; J. Anxiety
      Disorders, 9 (1995) 163). Assessment devices such as the Social Interaction
      Anxiety Scale, the Social Phobia Scale (SIAS and SPS; Behav. Res. Therapy, 36 (4)
      (1998) 455), and the Anxiety Sensitivity Index (ASI; Behav. Res. Therapy, 24
      (1986) 1) are good measures of the presumably separate lower-order factors. This
      study compared the effectiveness of the SIAS, SPS, ASI-physical scale and STAI-T
      (State-Trait Anxiety Inventory. Palo Alto, CA: Consulting Psychologists Press
      (1970)) as predictors of anxious response to a social challenge (asking an aloof
      confederate out on a date). Consistent with the hierarchical model of anxiety,
      the measures of trait anxiety were moderately correlated with each other and each
      was a significant predictor of anxious response. The specific measures of trait
      social anxiety were slightly better predictors of anxious response to the social
      challenge than was either the ASI-physical scale or the STAI-T. The results
      provide evidence of the predictive validity of these social trait measures and
      some support for their specificity in the prediction of anxious response to a
      social challenge.

PMID- 12051488
TI  - The liebowitz social anxiety scale as a self-report instrument: a preliminary
      psychometric analysis.
AB  - The Liebowitz social anxiety scale (LSAS) is a commonly used clinician
      administered instrument. The present study reports on the properties of a self
      report version of the LSAS (LSAS-SR). About 175 participants diagnosed with
      social phobia participated in the study. The LSAS-SR showed overall good
      psychometric properties as indicated by the results of test-retest reliability,
      internal consistency, and convergent and discriminant validity. Furthermore, the
      scale was sensitive to treatment change. The construct validity of the LSAS-SR,
      however, remains to be further explored. These findings support the utility of
      the LSAS-SR, which has the advantage of saving valuable clinician time compared
      to the clinician-administered version.

PMID- 12051489
TI  - The driving anger expression inventory: a measure of how people express their
      anger on the road.
AB  - Four ways people express their anger when driving were identified. Verbal
      Aggressive Expression (alpha=0.88) assesses verbally aggressive expression of
      anger (e.g., yelling or cursing at another driver); Personal Physical Aggressive
      Expression (alpha=0.81), the ways the person uses him/herself to express anger
      (e.g., trying to get out and tell off or have a physical fight with another
      driver); Use of the Vehicle to Express Anger (alpha=0.86), the ways the person
      uses his/her vehicle to express anger (e.g., flashing lights at or cutting
      another driver off in anger); and Adaptive/Constructive Expression (alpha=0.90),
      the ways the person copes positively with anger (e.g., focuses on safe driving or
      tries to relax). Aggressive forms can be summed into Total Aggressive Expression
      Index (alpha=0.90). Aggressive forms of expression correlated positively with
      each other (rs=0.39-0.48), but were uncorrelated or correlated negatively with
      adaptive/constructive expression (rs=-0.02 to -0.22). Aggressive forms of anger
      expression correlated positively with driving-related anger, aggression, and
      risky behavior; adaptive/constructive expression tended to correlate negatively
      with these variables. Differences in the strengths of correlations and regression
      analyses supported discriminant and incremental validity and suggested forms of
      anger expression contributed differentially to understanding driving-related
      behaviors. Theoretical and treatment implications were explored.

PMID- 12051490
TI  - Florida Board of Pharmacy disciplines PetMed Express, Savemax. Internet
      pharmacies given another chance.

PMID- 12051491
TI  - Dirty bombs, antimicrobials, and conservation.

PMID- 12051492
TI  - Sees global standards as solution to microchip frustration.

PMID- 12051493
TI  - Questions research methods of probiotics study.

PMID- 12051494
TI  - Thinks pregnant mare urine industry inhumane.

PMID- 12051495
TI  - Thinks pregnant mare urine industry inhumane.

PMID- 12051496
TI  - Sees flip side to Aesculapian authority.

PMID- 12051497
TI  - What is your diagnosis? A well-circumscribed gas and fluid-filled mass with a
      soft tissue perimeter in the dorsocaudal portion of the right hemithorax.

PMID- 12051498
TI  - How is my practice doing? How can I improve it?

PMID- 12051499
TI  - Metabolism of dietary essential fatty acids and their conversion to long-chain
      polyunsaturated metabolites.

PMID- 12051500
TI  - Characteristics of free-roaming cats and their caretakers.
AB  - OBJECTIVES: To describe the characteristics of unowned, free-roaming cats and
      their caretakers who participated in a trap-neuter-return (TNR) program and to
      determine the effect of the program on free-roaming cat colonies. DESIGN:
      Prospective study. SAMPLE POPULATION: 101 caretakers of 920 unowned, free-roaming
      cats in 132 colonies in north central Florida. RESULTS: Most (85/101; 84%)
      caretakers were female. The median age was 45 years (range, 19 to 74 years). Most
      (89/101; 88%) caretakers owned pets and of those, most (67/101; 66%) owned cats.
      The major reasons for feeding free-roaming cats were sympathy and love of
      animals. Most caretakers reported that the cats they cared for were too wild to
      be adopted, but many also reported that they considered the cats to be like pets.
      The total surveyed cat population was 920 before participation in TNR and 678
      after TNR. Mean colony size was 7 cats before TNR and 5.1 cats after TNR. Most
      cats lived on the caretaker's property. At the time of the survey, 70% (644/920)
      of the cats had been neutered. CONCLUSIONS AND CLINICAL RELEVANCE: The decrease
      in the surveyed free-roaming cat population was attributed to a reduction in
      births of new kittens, adoptions, deaths, and disappearances. Recognition of the
      human-animal bond that exists between caretakers and the feral cats they feed may
      facilitate the development of effective control programs for feral cat
      populations.

PMID- 12051501
TI  - Trusts for the care of animals.

PMID- 12051502
TI  - Use of a portable real-time reverse transcriptase-polymerase chain reaction assay
      for rapid detection of foot-and-mouth disease virus.
AB  - OBJECTIVE: To evaluate a portable real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR) assay designed to detect all 7 viral serotypes of foot
      and-mouth disease virus (FMDV). DESIGN: Laboratory and animal studies. STUDY
      POPULATION: Viruses grown in tissue culture and animals experimentally infected
      with FMDV. PROCEDURE: 1 steer, pig, and sheep were infected with serotype O FMDV.
      Twenty-four hours later, animals were placed in separate rooms that contained 4
      FMDV-free, healthy animals of the same species. Oral and nasal swab specimens,
      oropharyngeal specimens obtained with a probang, and blood samples were obtained
      at frequent intervals, and animals were observed for fever and clinical signs of
      foot-and-mouth disease (FMD). Samples from animals and tissue cultures were
      assayed for infectious virus and viral RNA. RESULTS: The assay detected viral RNA
      representing all 7 FMDV serotypes grown in tissue culture but did not amplify a
      panel of selected viruses that included those that cause vesicular diseases
      similar to FMD; thus, the assay had a specificity of 100%, depending on the panel
      selected. The assay also met or exceeded sensitivity of viral culture on samples
      from experimentally infected animals. In many instances, the assay detected viral
      RNA in the mouth and nose 24 to 96 hours before the onset of clinical disease.
      CONCLUSIONS AND CLINICAL RELEVANCE: The assay reagents are produced in a
      vitrified form, which permits storage and transportation at ambient temperatures.
      The test can be performed in 2 hours or less on a portable instrument, thus
      providing a rapid, portable, sensitive, and specific method for detection of
      FMDV.

PMID- 12051503
TI  - Diagnosis of hyperadrenocorticism in dogs: a survey of internists and
      dermatologists.
AB  - OBJECTIVE: To determine testing protocols used by board-certified internists and
      dermatologists for diagnosis of hyperadrenocorticism (HAC) in dogs. DESIGN:
      Survey. STUDY POPULATION: Board-certified internists and dermatologists.
      PROCEDURE: A questionnaire was mailed to 501 specialists to gather information
      pertaining to diagnosis of HAC. RESULTS: 206 surveys were returned. Only 26% of
      respondents indicated they would screen a dog for HAC if the dog had only a few
      laboratory abnormalities consistent with HAC and no clinical signs consistent
      with the disease; 31% indicated they would not, and 43% indicated they would
      sometimes. Overall, 55% of respondents indicated they preferred to use the low
      dose dexamethasone suppression test for routine screening of dogs suspected to
      have HAC. However, many respondents indicated they would use a different
      screening test than usual in particular circumstances. Sixty-eight percent of
      respondents indicated they would perform a second screening test for confirmation
      if results of an initial screening test were positive but there were few clinical
      or laboratory abnormalities consistent with HAC. Most respondents used some sort
      of test to differentiate pituitary-dependent HAC from HAC secondary to an adrenal
      tumor (AT), but no 1 test was clearly preferred. Ultrasonography was commonly
      used, whereas computed tomography and magnetic resonance imaging were not, even
      if available. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that the low
      dose dexamethasone suppression test is the test most commonly used to screen dogs
      for HAC but that other tests may be used in certain circumstances. A variety of
      tests were used to differentiate pituitary-dependent HAC from HAC secondary to an
      AT.

PMID- 12051504
TI  - Use of cabergoline to treat primary and secondary anestrus in dogs.
AB  - OBJECTIVE: To determine whether cabergoline would be safe and effective for
      induction of estrus in dogs with primary or secondary anestrus. DESIGN:
      Prospective case series. ANIMALS: 6 privately owned otherwise healthy pure-bred
      dogs with primary or secondary anestrus. PROCEDURE: Dogs were treated with
      cabergoline (5 microg/kg [2.3 microg/lb], p.o., q 24 h) until 2 days after the
      onset of proestrus. Follicular development was assessed by means of cytologic
      examination of vaginal smears; ovulation was assessed by measuring serum
      progesterone concentration 3 weeks after the onset of estrus. Five bitches were
      mated during behavioral estrus. RESULTS: All dogs had normal estrus periods, and
      all 5 dogs that were mated whelped normal litters. Mean duration of cabergoline
      treatment was 16 days. None of the dogs had any adverse effects associated with
      cabergoline administration. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that administration of cabergoline is safe and effective for treatment for
      primary and secondary anestrus in dogs.

PMID- 12051506
TI  - Pulmonary mycobacteriosis caused by Mycobacterium haemophilum and M. marinum in a
      royal python.
AB  - An adult female royal python was referred with an 18-month history of chronic
      respiratory tract disease. Anemia and moderate leukocytosis with heterophilia and
      monocytosis were detected and interpreted as evidence of a chronic inflammatory
      condition. Evaluation of lateral and dorsoventral radiographic views revealed
      multiple soft-tissue opacities within the cranial lung fields. Endoscopic
      evaluation revealed that the normal reticulated pattern on the surface of the
      lung had been largely replaced by diffuse, granulomatous tissue. Histologic
      examination of biopsy specimens revealed classic pyogranulomas. Ziehl-Neelsen
      stains revealed numerous acid-fast bacilli consistent with Mycobacterium spp.
      Molecular methods including polymerase chain reaction restriction assays and DNA
      sequencing confirmed the identification of M. haemophilum and M. marinum. The
      snake was euthanatized. Mycobacteriosis is an uncommon and sporadic
      pyogranulomatous disease of reptiles. In most cases of reptile mycobacteriosis,
      treatment is not advised because of the chronic nature and often advanced stage
      of the disease, long-term and expensive nature of potential treatment regimens,
      and the risk of spread to other animals, including humans.

PMID- 12051505
TI  - Use of three infusion pumps for postoperative administration of buprenorphine or
      morphine in dogs.
AB  - Results of using an implantable osmotic pump, a preset disposable infusion pump,
      or a reusable programmable infusion pump for postoperative administration of
      buprenorphine or morphine in dogs undergoing abdominal surgery are described. Ten
      dogs underwent abdominal surgery for implantation of vascular access ports. Dogs
      were given buprenorphine s.c. by use of an implantable osmotic pump (4 dogs),
      morphine s.c. by use of a preset infusion pump (4), or buprenorphine intra
      arterially by use of a programmable infusion pump (2). Dogs were monitored, and
      serum buprenorphine or morphine concentration was measured for 72 hours after
      surgery; pumps were removed 48 hours after surgery. Severity of pain was
      determined by assigning a pain score. The preset infusion pump and the
      programmable infusion pump resulted in comparable pain relief and sustained serum
      analgesic concentrations throughout the recovery period. However, the cost of the
      pumps and other associated factors may limit their use to dogs undergoing
      invasive surgical procedures expected to result in substantial postoperative
      pain. The level of analgesia obtained with the implantable osmotic pumps was
      inconsistent.

PMID- 12051507
TI  - Massive transfusion in dogs: 15 cases (1997-2001).
AB  - OBJECTIVE: To determine clinical characteristics of dogs that received massive
      transfusion and identify the underlying diseases, complications, and outcomes.
      DESIGN: Retrospective study. ANIMALS: 15 dogs. PROCEDURE: Medical records of dogs
      receiving a massive blood transfusion were evaluated for transfusion volume,
      underlying disease process or injury, benefits and complications of transfusion,
      and outcome. A massive transfusion was defined as transfusion of a volume of
      blood products in excess of the patient's estimated blood volume (90 ml/kg [40
      ml/lb]) in a 24-hour period or transfusion of a volume of blood products in
      excess of half the patient's estimated blood volume in a 3-hour period. RESULTS:
      Six dogs had intra-abdominal neoplasia resulting in hemoabdomen, 3 had suffered a
      traumatic incident resulting in hemoabdomen, and 6 had non-traumatic, non
      neoplastic blood loss. Mean volumes of packed RBC and fresh-frozen plasma
      administered were 66.5 ml/kg (30 ml/lb) and 22.2 ml/kg (10 ml/lb), respectively.
      All dogs evaluated developed low ionized calcium concentrations and
      thrombocytopenia. Transfusion reactions were recognized in 6 dogs. Four dogs
      survived to hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggest that massive transfusion is possible and potentially successful in dogs.
      Predictable changes in electrolyte concentrations and platelet count develop.

PMID- 12051508
TI  - Surgical and nonsurgical management of and selected risk factors for spontaneous
      pneumothorax in dogs: 64 cases (1986-1999).
AB  - OBJECTIVE: To compare results of surgical versus nonsurgical treatment of
      spontaneous pneumothorax in dogs. DESIGN: Retrospective study. ANIMALS: 64 dogs
      with pneumothorax without any history of antecedent trauma. PROCEDURE:
      Information on signalment, thoracic radiographic findings, treatment, histologic
      findings, and outcome was obtained from the medical records. Signalment of
      affected dogs was compared with signalment of a control population of 260 dogs
      examined by the emergency service for reasons other than pneumothorax during the
      study period. RESULTS: Siberian Huskies were overrepresented in the case
      population, compared with the control population of dogs examined by the
      emergency service for other reasons. Twenty-eight dogs were treated without
      surgery (ie, thoracocentesis or tube thoracostomy with or without cage rest), and
      36 were treated with surgery. Information regarding final outcome was available
      for 33 dogs treated with surgery (median follow-up time, 485 days) and 15 dogs
      treated without surgery (median follow-up time, 366 days). Dogs that underwent
      surgery had significantly lower recurrence (1/30) and mortality (4/33) rates,
      compared with dogs treated without surgery (6/12 and 8/15, respectively). A
      definitive diagnosis was obtained for 38 dogs, including 34 of 36 dogs undergoing
      surgery; 26 had bullous emphysema and 4 had neoplasia. Two dogs developed
      spontaneous pneumothorax secondary to migration of plant foreign bodies.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that recurrence and mortality
      rates for dogs with spontaneous pneumothorax managed surgically were
      significantly lower than rates for dogs managed by nonsurgical means alone. Early
      surgical intervention is recommended for definitive diagnosis and treatment of
      dogs with spontaneous pneumothorax.

PMID- 12051509
TI  - Clinical findings associated with prairie rattlesnake bites in dogs: 100 cases
      (1989-1998).
AB  - OBJECTIVE: To identify clinically relevant variables and treatments for dogs
      bitten by prairie rattlesnakes (Crotalus viridis viridis). DESIGN: Retrospective
      study. ANIMALS: 100 client-owned dogs. PROCEDURE: Records of dogs evaluated for
      rattlesnake envenomation from 1989 to 1998 were reviewed. Analysis was performed
      to test for significant associations among clinical variables or treatments and
      cell counts, costs, and duration of hospitalization. RESULTS: Most prairie
      rattlesnake bites occurred between May and September. Dogs were 3 months to 12
      years old (median, 3.7 years); most were bitten on the head in the late
      afternoon. There was no sex predilection. Median time to evaluation was 1 hour
      (range, 15 minutes to 13 hours). Swelling in the area of the bite was the primary
      physical abnormality. Principal initial laboratory findings were echinocytosis,
      thrombocytopenia, leukocytosis, and prolonged activated clotting time. Ninety
      four dogs were hospitalized; 48 were discharged the following day. Antimicrobials
      and crystalloid fluids, glucocorticoids, antihistamines, and antivenin
      administered i.v. were the most commonly used treatments. One dog died, and small
      dogs were hospitalized longer than large dogs. Antivenin administration was not
      significantly associated with duration of hospitalization but was associated with
      higher platelet counts after treatment and higher total hospital costs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Prairie rattlesnake envenomation in dogs is
      associated with high morbidity rate but low mortality rate. The efficacy of
      administration of antivenin for dogs with bites from this snake species is
      questionable.

PMID- 12051510
TI  - Association between the strength of serologic recognition of bovine leukosis
      virus and lymphocyte count in bovine leukosis virus-infected cows.
AB  - OBJECTIVE: To determine whether strength of serologic recognition of bovine
      leukosis virus (BLV) by use of ELISA is associated with blood lymphocyte counts.
      DESIGN: Prospective study. ANIMALS: 161 cows with positive results of ELISA for
      BLV. PROCEDURE: Sample-to-positive ratio (S:P), which is the ratio between the
      test sample and a positive control sample, was compared among lymphocytotic and
      nonlymphocytotic cows. A regression model was constructed to evaluate the
      association between blood lymphocyte concentration and S:P, age, and the
      interaction of these terms. RESULTS: Mean S:P differed significantly between
      lymphocytotic (2.58 +/- 0.36) and nonlymphocytotic (2.38 +/- 0.39) cows. Age and
      S:P were significantly associated with lymphocyte count. CONCLUSIONS AND CLINICAL
      RELEVANCE: Sample-to-positive ratio and lymphocyte count were related; however,
      cows with high S:P were not always lymphocytotic. Culling cows on the basis of
      S:P will reduce the herd load of infectious virus faster than random culling of
      ELISA-positive cows; however, culling on the basis of lymphocyte count will
      eliminate a greater proportion of the reservoir of infection.

PMID- 12051511
TI  - Assessment of test results when using a commercial enzyme-linked immunosorbent
      assay for diagnosis of paratuberculosis in repeated samples collected from adult
      dairy cattle.
AB  - OBJECTIVE: To determine the proportion of adult cattle that change test status
      when an ELISA for antibodies against Mycobacterium avium subsp paratuberculosis
      (MAP) is used to assay samples collected twice at variable intervals and to
      determine whether cows with an initial strong positive result were more likely to
      maintain positive status, compared with all cows with an initial positive result.
      DESIGN: Cross-sectional observational study. ANIMALS: 3,757 adult dairy cattle.
      PROCEDURE: Serum samples were obtained twice from cattle at intervals ranging
      from 77 to 600 days between collections. Samples were tested with an ELISA for
      detection of antibodies to MAP. RESULTS: Of 157 cattle with initial positive
      results (value for the sample divided by the value for positive-control serum
      [S/P] > or = 0.25), 62 (39.5%) had negative results for the second sample. Of 71
      cattle with an initial S/P value > or = 0.40, 13 (18.3%) had a negative result
      (S/P < 0.25) for the second sample. Of 33 cattle with an initial S/P > or = 0.70,
      3 (9.1%) had a negative result (S/P value < 0.25) for the second sample. Interval
      between collection of samples did not affect results. CONCLUSIONS AND CLINICAL
      RELEVANCE: Many cows changed ELISA status between samples collected at variable
      intervals. Cows with an initial high S/P value (> or = 0.70) were more likely to
      maintain positive status than cows classified as positive on the basis of cutoff
      values of > or = 0.25 or > or = 0.40. Veterinarians should expect variability in
      ELISA results when repeated testing of cattle is used as part of an MAP control
      program.

PMID- 12051512
TI  - Effects of administration of antimicrobials in feed on growth rate and feed
      efficiency of pigs in multisite production systems.
AB  - OBJECTIVE: To evaluate effect of various regimens for administration of
      antimicrobials in feed on growth rate and feed efficiency (feed/gain) of pigs in
      multisite production systems. DESIGN: Controlled trial. ANIMALS: 24,099 growing
      pigs in 3 multisite production systems. PROCEDURE: 10 trials involving various
      regimens for administration of antimicrobials in feed were evaluated. Trial 1
      compared effects of 2 antimicrobial regimens on finishing pig performance. Trials
      2 through 10 compared growth rate and feed efficiency of nursery and finishing
      pigs given antimicrobials in feed with values for control pigs not given
      antimicrobials. RESULTS: In trial 1, no significant differences were observed
      between the 2 antimicrobial regimens. In the remaining trials, growth rate of
      nursery pigs fed antimicrobials was significantly improved, compared with growth
      rate of control pigs. However, growth rate of finishing pigs and feed efficiency
      of nursery and finishing pigs were not significantly improved by adding
      antimicrobials to the feed. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest
      that use of antimicrobials in the feed to promote growth should be limited to the
      nursery phase in multisite pig production systems. Use of antimicrobials in the
      feed of finishing pigs should be limited to therapeutic applications in which a
      diagnosis of bacterial infection susceptible to the antimicrobial to be used has
      been confirmed.

PMID- 12051513
TI  - Portosystemic shunt in an alpaca cria.
AB  - A 5-month-old alpaca cria was examined for chronic poor growth and repeated
      episodes of diarrhea. Examination of feces for parasites yielded negative
      results. Serum bile acid and blood ammonia concentrations were high. Subsequent
      examination by ultrasonography, percutaneous splenic portography, and colonic
      scintigraphy did not reveal evidence of a portosystemic vascular anomaly.
      Exploratory celiotomy with mesenteric vein portography revealed a colonic vein
      shunt in the caudal portion of the abdomen from the caudal vena cava to the
      portal vein. The shunt vessel was ligated without incident. Following surgery,
      the cria began to gain weight and was more alert. Eighteen months after surgery,
      the cria was doing well, although it had loose feces and was slightly small for
      its age. Portosystemic shunts are rare in cattle and horses but should be
      considered in alpacas with chronic poor growth when parasitism has been ruled
      out.

PMID- 12051514
TI  - Adrenocorticotrophic hormone (ACTH) stimulation of sheep fetal adrenal cortex can
      occur without increased expression of ACTH receptor (ACTH-R) mRNA.
AB  - In the present study, it was hypothesized that the adrenocorticotrophin hormone
      receptor (ACTH-R) would be up-regulated in the adrenal gland of the sheep fetus
      following infusion of physiological amounts of ACTH, as shown for adrenal
      cortical cells in culture. In chronically catheterized sheep, an intravenous
      infusion of ACTH(1-24) was given to 6 fetuses for 24 h at a rate of 0.5 microg h(
      1), starting on Day 126 or 127 of gestation (term approximately 147 days). Four
      control fetuses received an infusion of vehicle (saline). Total RNA was extracted
      from the fetal adrenal glands by the guanidinium thiocyanate method. Expression
      of specific mRNAs was determined by ribonuclease protection assay using cRNA
      probes directed against: ACTH-R; the steroid enzymes side-chain cleavage
      (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17apha-hydroxylase
      (P450c17) and 21beta-hydroxylase (P450c21); and beta-actin. Ratios of mRNA
      expression to beta-actin mRNA expression (arbitrary units) were calculated to
      correct for differences in RNA quality between samples. The concentration (mean
      +/- SEM) of immunoreactive cortisol in fetal plasma was greater after ACTH
      infusion than after vehicle infusion (47 +/- 3 v. 13 +/- 2 ng mL(-1)
      respectively; P<0.001). Adrenal expression of P450scc and P450c21 mRNA increased
      after ACTH infusion (P<0.05), whereas expression of P450c17 and 3beta-HSD mRNA
      was unchanged. There was no difference in ACTH-R mRNA expression between ACTH-
      and vehicle-infused fetuses (254 +/- 48 v. 305 +/- 76 arbitrary units
      respectively). It was concluded that ACTH is able to increase plasma cortisol
      concentrations in the sheep fetus by up-regulating cortisol synthesis in the
      adrenal gland, but that in vivo this does not require up-regulation of ACTH-R
      mRNA.

PMID- 12051515
TI  - The effect of a partial Y chromosome deletion in B10.BR-Ydel mice on testis
      morphology, sperm quality and efficiency of fertilization.
AB  - Males of the mouse strain B10.BR/SgSn and its congenic mutant strain B10.BR-Ydel,
      with a partial deletion of the Y chromosome, were used to examine factors related
      to poor sperm quality and quantity in the mutant strain. The testes of males from
      the two strains did not differ in their immunohistochemical reaction to androgen
      receptors or in the number of Sertoli and germ cells in tubules with normal
      morphology. However, mutants showed a greater frequency of degenerated tubules, a
      higher level of X-Y chromosome dissociation at meiosis (18% v. 10% in control
      males), and a lower content of resistant sperm heads in testis homogenates. In
      the cauda epididymidis, there was a higher percentage of spermatozoa with
      abnormal heads (88% v. 31%) and of spermatozoa with a cytoplasmic droplet still
      attached (74% v. 51%). Many sperm heads with flat acrosomes, occurring only in
      mutants (30% of sperm population), were deficient in proteolytic enzymes, as
      evidenced by the reaction on gelatine membranes. Most copulations of mutant males
      (11/18) were sterile in spite of the presence of spermatozoa in the uterus, but
      in the remaining copulations the fertilization rate was reasonably good (79%).
      Low numbers of spermatozoa were recovered from the oviducts, and those with the
      most severely deformed heads were less frequent there than in the uterus. The
      results show that a partial deletion of the Y chromosome affects efficiency of
      spermatogenesis, morphology of spermatozoa, their epididymal maturation and
      capacity to reach the ampulla and fertilize eggs.

PMID- 12051516
TI  - Investigation of factors affecting pregnancy rate after embryo transfer in the
      dromedary camel.
AB  - The uteri of 36 adult dromedary camels were flushed non-surgically three times
      each with 90-120 mL of embryo flushing medium 7 days after ovulation. A total of
      242 embryos were recovered, of which 139 were transferred non-surgically to
      recipient camels that were either at different levels of synchrony with respect
      to the Day 7 donor (+1 to -3 days; n = 58), or were at Day 6 after ovulation, but
      received one of the following treatments: (i) none (controls, n = 15); (ii) 150
      mg progesterone-in-oil injected intramuscularly once daily during Days 5-20 after
      ovulation inclusive (n = 16); (iii) 500 mg flunixin meglumine given intravenously
      15 min before transfer of the embryo (n = 6); (iv) 20 microg of the gonadotrophin
      releasing hormone (GnRH) analogue buserelin given on Day 5 after ovulation (n =
      12); or (v) the embryo was cooled to 4 degrees C and held at this temperature in
      an insulated container for 24 h before being transferred (n = 32). Jugular vein
      blood samples, taken daily from all the recipient camels during Days 0-20 after
      ovulation, were assayed for progesterone concentration and closely timed serial
      samples taken from the camels receiving flunixin meglumine or GnRH were assayed
      for 13,14-dihydro-15-keto prostaglandin F2alpha (PGFM) or oestradiol
      concentrations. The pregnancy rate increased to a maximum of 67% when ovulation
      in the recipient was negatively synchronized to have occurred 1 day behind that
      in the donor, and it fell dramatically when the level of asynchrony between
      recipient and donor increased to +1 (9%) or -3 (10%) days. It was not improved by
      daily injections of progesterone (44%), flunixin meglumine given before transfer
      (16%), or GnRH given on Day 5 (33%). Of the 32 embryos that were cooled to 4
      degrees C before being transferred to Day 6 recipients, 20 resulted in
      pregnancies (63%) to give a success rate similar to that attained with the
      control fresh embryos (67%). Serum progesterone concentrations in the recipients
      increased to a mean +/- SEM of 2.6 +/- 0.8 ng mL(-1) by Day 8 after ovulation
      and, in those that were pregnant, levels remained elevated at 3-5 ng mL(-1) for
      the remainder of the sampling period; in non-pregnant recipients the
      concentrations declined to <1 ng mL(-1) by Day 11. Plasma PGFM concentrations in
      the flunixin meglumine-treated camels remained low (40-90 pg mL(-1)) compared
      with those in the untreated control camels, in which peak values of around 180 pg
      mL(-1) were reached within 10 min after transfer after which a steady decline
      occurred until resting concentrations of 90-100 pg mL(-1) were reached by 110 min
      after transfer. Treatment with GnRH on Day 5 after ovulation produced a
      transitory increase in serum oestradiol-17beta concentrations for 24 h. However,
      from Day 8, oestradiol concentrations in both the GnRH-treated and the untreated
      camels increased steadily to reach 2.5-3.5 pg mL(-1) by Day 12.

PMID- 12051517
TI  - Oxidative stress and altered prostanoid production in the placenta of
      streptozotocin-induced diabetic rats.
AB  - The oxidative stress in placental tissues during late pregnancy, as well as the
      relationship between reactive oxygen species (ROS) and the arachidonic acid (AA)
      pathway was evaluated in a neonatal streptozotocin (STZ)-induced diabetic rat
      model. Lipoperoxide levels are increased in diabetic tissues compared with
      control tissues (P<0.001) and they seem to increase throughout the development of
      gestation both in control (P<0.05) and STZ-induced diabetic (P<0.001) rats.
      Superoxide dismutase (SOD) activity is not modified on different days of
      pregnancy, but enzymatic activity is lower in diabetic tissues than in control
      tissues (P<0.01). Labour is preceded by an increase in placental 14C
      prostaglandin conversion from 14C-AA in control and diabetic animals (P<0.05) and
      the thromboxane B2 (TXB2)/6-keto-prostaglandin F1alpha (PGF1alpha) ratio is
      higher in diabetic placental tissues than in controls. The addition of SOD and
      glutathione to the incubation medium does not modify prostanoid levels in control
      rats, but does decrease the AA conversion to PGF2alpha, PGE2 and TXB2 (P<0.05) in
      diabetic placenta. Superoxide radical generation (hypoxanthine/xanthine oxidase
      or hydrogen peroxide added to the incubation medium) produces a decrease in 6
      keto-PGF1alpha (P<0.05) in control and diabetic tissues, whereas PGF2alpha, PGE2
      and TXB2 levels, and PGF2alpha and TXB2 production are increased in control and
      diabetic animals respectively (P<0.05). Diabetic pregnant rats supplemented with
      a diet containing 400 mg day(-1) of alpha-tocopherol (vitamin E) have diminished
      placental PGF2alpha and TXB2 production and lipoperoxide levels. The results show
      a higher TXB2 and a decreased 6-keto-PGF1alpha placental production that may be
      linked to increased oxidative stress and to a reduced antioxidant capacity in STZ
      induced diabetic rats. These imbalances, probably involved in abnormal placental
      structure and function, may potentially be corrected with dietary supplementation
      of alpha-tocopherol in diabetic pregnancies.

PMID- 12051518
TI  - Lecithin-cholesterol acyltransferase activity during maturation of human
      preovulatory follicles with different concentrations of ascorbate, alpha
      tocopherol and nitrotyrosine.
AB  - The enzyme lecithin-cholesterol acyltransferase (LCAT) transfers an acyl chain
      from lecithin to cholesterol or oestradiol, thus playing a crucial role in
      reverse cholesterol transport and follicular synthesis of potent long-lived
      oestrogens. The mechanism of catalysis is biphasic, as it is based on a
      phospholipase and an esterifying activity. Sulfhydryl groups were previously
      reported to be required for the esterification step. Lecithin-cholesterol
      acyltransferase has previously been shown to be inhibited by thiol oxidants such
      as peroxynitrite. Peroxynitrite also converts tyrosine to nitrotyrosines. In the
      present study, high levels of nitrotyrosine associated with low LCAT activity,
      and vice versa, were found in human preovulatory follicular fluids. Follicular
      fluids were also analysed for oestradiol (E) and progesterone (P) concentrations.
      The E/P ratio, which decreases as ovulation approaches, was used to evaluate the
      maturation status of each follicle. Enzyme activity was negatively correlated
      with the E/P ratio. Ascorbate (Asc) and alpha-tocopherol (Toc) were titrated in
      follicular fluid and plasma to evaluate their accumulation or consumption in the
      follicle. High LCAT activity was found in follicular fluids where Asc and Toc had
      accumulated, whereas lower activity was associated with Asc and Toc consumption.
      The consumption of both antioxidants was positively correlated with the E/P
      ratio. The results suggest that as follicle maturation progresses, Toc and Asc
      concentrations increase in follicular fluid, thus protecting LCAT from oxidative
      damage and loss of activity.

PMID- 12051519
TI  - Levels of endothelin-1 in embryos from control and neonatal streptozotocin
      induced diabetic rats, and their relationship with nitric oxide generation.
AB  - Endothelin-1 (ET-1), a potent vasoconstrictor peptide and modulator of vasoactive
      substances such as prostanoids and nitric oxide (NO), plays an important role
      during embryo and fetal development. In this work, ET-1, nitrate and nitrite, and
      prostaglandin E2 (PGE2) levels in embryos from control and neonatal
      streptozotocin-induced (n-stz) diabetic rats were assessed, and the modulatory
      pathways regulating the generation of these vasoactive agents investigated.
      Endothelin-1 concentrations were found to be increased in embryos from n-stz
      diabetic rats when compared with controls. Additions of spermine NONOate, a
      nitric oxide donor, enhanced ET-1 levels in embryos from both control and n-stz
      diabetic rats, whereas N(G)-monomethyl-L-arginine, a nitric oxide inhibitor,
      diminished embryonic ET-1 content. Thus, enhanced ET-1 levels in the embryos from
      n-stz diabetic rats may be related to the elevated NO levels found in those
      embryos. Additions of ET-1 or bosentan (an endothelin A and endothelin B receptor
      antagonist), did not alter PGE2 generation in embryos from either control or n
      stz diabetic rats. Endothelin-1 additions diminished nitrate and nitrite levels
      in embryos from both control and n-stz diabetic rats, whereas bosentan stimulated
      nitrate and nitrite generation in those embryos. In the present work, it was
      found that ET-1 levels were enhanced in embryos from n-stz diabetic rats,
      probably as a result of NO overproduction, an alteration which may be related to
      embryonic abnormalities and growth delay. Endothelin-1 has been shown to be a
      negative modulator of embryonic NO levels, a mechanism likely to be important
      during development. Endothelin-1 may prevent damage induced by NO overproduction
      in embryos from n-stz diabetic rats.

PMID- 12051520
TI  - Control of fertility in the red fox (Vulpes vulpes): effect of a single oral dose
      of cabergoline in early pregnancy.
AB  - Single oral doses of 100 microg kg(-1) cabergoline (CAB) were previously found to
      affect the reproductive success of silver fox (Vulpes vulpes) vixens from Day 28
      post insemination (PI) onwards by causing abortions and postnatal mortality. The
      present trial investigated the effect of a single oral dose of 100 microg kg(-1)
      CAB given to farmed silver fox vixens at 7, 14, 21 or 28 days PI. Six vixens were
      dosed with CAB at each day PI and abortions, total post-partum litter loss and
      the combined effects of both were compared with a group of vixens that received a
      placebo and a control group of vixens that received no treatment. No significant
      difference existed between the placebo and control groups in the incidence of
      abortion, postnatal litter loss and litter size at 3 weeks post partum. Overall,
      a significantly higher frequency of abortions were detected in vixens dosed with
      CAB (6/24) compared with the combined placebo and control (0/41) groups (P<0.01).
      Cabergoline administration was significantly associated with complete litter loss
      (P<0.01) and the combined effects of abortion and litter loss (P<0.001). Oral CAB
      significantly reduced the reproductive success of vixens when given at Day 21 and
      Day 28 PI, but not at Day 7 and Day 14 PI.

PMID- 12051521
TI  - Effect of intermittent umbilical cord occlusion on fetal respiratory activity and
      brain adenosine in late-gestation sheep.
AB  - It was hypothesized that intermittent umbilical cord occlusion (UCO) would
      inhibit ovine fetal breathing movements (FBM) in association with increased
      cerebral adenosine levels. To test this hypothesis, on two successive days during
      late gestation (133-134 days; term = 146 days), microdialysis samples were
      collected from the brains of 10 chronically instrumented fetal sheep during 2-h
      periods of complete UCO induced every 30 min (Day 1: 2-min UCOs; Day 2: 4-min
      UCOs). Control fetuses (n = 10) underwent no UCO. Tracheal pressure was measured
      throughout. This regimen resulted in a decrease in fetal arterial PO2 (PaO2)
      during each UCO to 7.3 +/- 0.8 mmHg (P<0.01; Day 1) and 8.4 +/- 1.1 mmHg (P<0.01;
      Day 2). Throughout each UCO period, fetal arterial pH (pHa) decreased to 7.28 +/-
      0.02 (P<0.01; Day 1) and 7.11 +/- 0.07 (P<0.01; Day 2). The hourly incidence of
      FBM decreased significantly only on Day 2, from 38.6 +/- 4.1% to 4.1 +/- 1.6%
      (P<0.01). The frequency of deep isolated inspiratory efforts increased from 4.7
      +/- 2.0 h(-1) to 17.6 +/- 6.1 h(-1) (P<0.05; Day 1) and from 2.2 +/- 0.9 h(-1) to
      33.6 +/- 4 h(-1) (P<0.01; Day 2). The amplitude of both FBM and deep isolated
      inspiratory efforts increased during the UCO periods on both days. The
      concentration of cerebral extracellular fluid (ECF) adenosine during UCO
      increased by 219 +/- 215% (P<0.05; Day 1) and 172 +/- 107% (P<0.05; Day 2) over
      the baseline periods. In conclusion, the severity of the inhibitory effect of
      repeated UCO on FBM depends, in part, on the length of the occlusions. The
      inhibition of FBM during intermittent UCO may be mediated by the increase in ECF
      adenosine in the fetal brain. Furthermore, FBM and deep isolated inspiratory
      efforts appear to be regulated by different mechanisms.

PMID- 12051522
TI  - Delayed ovulation and parturition in a viviparous alpine lizard (Niveoscincus
      microlepidotus): morphological data and plasma steroid concentrations.
AB  - The southern snow skink, Niveoscincus microlepidotus, exhibits an unusual
      biennial reproductive cycle with an extended gestation period of approximately 1
      year. Morphological data were gathered on a monthly basis, providing a detailed
      picture of the reproductive cycle. Vitellogenesis begins in spring, immediately
      after parturition. Maximum follicular diameter is reached before the winter
      hibernation period and ovulation occurs the following spring. Embryos are fully
      developed and reach maximum size by early autumn. Yolk reserves are depleted
      before winter. Birth of between one and four young occurs the following spring.
      Plasma progesterone concentrations are low (2.7 +/- 0.9 ng mL(-1)) in post-partum
      females, begin to rise in autumn in vitellogenic females and peak (38.5 +/- 7.9
      ng mL(-1)) in pre-ovulatory females after hibernation. Concentrations are high
      (15.4 +/- 5.9 ng mL(-1)) in early pregnancy and decline to basal levels before
      winter and well before birth in spring. Plasma oestradiol concentrations peak
      during vitellogenesis (1.0 +/- 0.3 ng mL(-1)) and decline to basal levels during
      pregnancy (0.2 +/- 0.03 ng mL(-1)). A second oestradiol peak occurs before
      parturition (0.7 +/- 0.2 ng mL(-1)). Thus, functional completion of
      vitellogenesis and gestation is achieved by autumn in successive years. The
      mechanisms that defer ovulation and parturition by a further six months are
      unknown.

PMID- 12051524
TI  - The effects of inbreeding on testicular sperm concentration in Peromyscus
      polionotus.
AB  - Inbreeding effects on fitness have most often been quantified via juvenile
      mortality. However, inbred adults may suffer from inbreeding depression if their
      fertility or fecundity is compromised as a consequence of inbreeding. Here, the
      effects of inbreeding on male fertility in oldfield mice, Peromyscus polionotus,
      were examined. Testicular sperm concentration was assessed in 93 males, 68 of
      which were paired for breeding. Forty of the 68 paired males failed to produce
      offspring. Total testicular sperm count, sperm count (g testis)(-1), and testis
      mass all declined significantly with increasing inbreeding coefficient. Sperm
      concentration did not significantly impact reproductive success. Although sperm
      concentration in males of most species can decline to low levels before
      reproductive impairment is detectable, the declines in testicular sperm
      concentration found here suggest that inbreeding can affect fertility in adult
      males. Furthermore, monitoring testicular sperm concentration could provide a
      mechanism to monitor potential declines in reproductive performance before
      population-level reproductive success is irreparably impaired. The implications
      for the management of small, captive and wild populations may be substantial.

PMID- 12051523
TI  - Follicle size and oocyte diameter in relation to developmental competence of
      buffalo oocytes in vitro.
AB  - Follicular size, oocyte morphology and diameter were investigated for their
      possible relationship with in vitro developmental competence of buffalo oocytes.
      Cumulus oocytes complexes (COCs), aspirated from small (<3 mm), medium (3-8 mm)
      and large (>8 mm) follicles of normal ovaries and cystic ovarian follicles of
      abattoir-derived ovaries, were graded for their morphological appearance and were
      cultured to assess their developmental competence. The influence of cystic
      follicles on maturational competence of COCs recovered from co-existing follicles
      of cystic ovaries was studied. The mean diameter of oocytes from follicles of
      different size were examined, and the influence of oocyte diameter--(i) <126
      microm; (ii) 127-144 microm; (iii) 145-162 microm; and (iv) >163 microm--on in
      vitro maturation, cleavage and embryo yield was studied. Results suggested that
      increased fertilization, cleavage and embryo development were significantly
      (P<0.05) higher in COCs aspirated from large follicles, followed by medium and
      small-sized normal follicles, and the presence of cystic follicles had no
      significant (P<0.05) effect on the maturation competence of the COCs recovered
      from co-existing follicles. The mean diameter of the buffalo oocyte obtained from
      normal ovaries was found to be 146.4 microm and the rate of blastocyst production
      in vitro was significantly higher (P<0.05) in oocytes with diameters greater than
      145 microm. In conclusion, the larger the size of the follicles and oocytes, the
      greater the developmental competence in vitro of buffalo oocytes.

PMID- 12051525
TI  - Tracing sperm acrosome differentiation in the testis and maturation in the
      epididymis of the tammar wallaby (Macropus eugenii) with a 45-kDa acrosome
      membrane-associated protein.
AB  - A 45-kDa protein was originally extracted from a depression, where the acrosome
      is lodged, on the anterior end of the sperm nucleus of ejaculated wallaby
      spermatozoa. Using immunofluorescent and confocal microscopes, this study
      demonstrates that the 45-kDa protein is persistently localized to the sperm
      acrosome throughout the periods of spermiogenesis, spermiation, epididymal
      maturation and ejaculation in the tammar wallaby. The distribution of the 45-kDa
      protein is always on the perimeter of the acrosome and associated with the
      acrosomal membrane, so that changes in the shape of the 45-kDa immunofluorescent
      labelling mirror changes in the shape of the acrosome during its differentiation
      in the testis and epididymis. Thus, the 45-kDa protein may be used as a molecular
      marker to study the marsupial acrosome differentiation and to chart the events of
      testicular and epididymal maturation of the spermatozoa. Furthermore, the
      behaviour of the 45-kDa protein during the immunostaining process suggests that
      this protein is a largely insoluble and detergent-resistant protein and may play
      an important role in attachment of the acrosome to the nucleus during sperm
      formation, similar to those inner acrosomal-membrane-associated proteins that
      have been reported in eutherian spermatozoa.

PMID- 12051526
TI  - Prediction of stage of pregnancy in prolific sheep using ultrasound measurement
      of fetal bones.
AB  - The use of ultrasound to estimate stage of pregnancy was assessed in 32 ewes of a
      prolific genotype carrying 7 singleton fetuses and 9 twin, 10 triplet and 6
      quadruplet litters that were scanned on six occasions from 60 to 120 days of
      gestation. At least one ultrasound measurement per ewe of fetal metacarpal bone
      length (MCL), biparietal diameter (BPD), or of both bones was made on over 90% of
      attempts (n = 152). Measurement of MCL was made on 78% of attempts (n = 371), of
      BPD on 73% of attempts, and of both bones on 62% of attempts. The equation
      developed from BPD (mean absolute error (MAE) = 3.2 days) was similar to that
      developed from measurement of MCL (MAE = 3.3 days) in its capacity to predict
      stage of pregnancy. Accuracy of prediction was improved using equations that
      included mean values within litters for BPD (MAE = 2.5 days) and MCL (MAE = 2.6
      days). Further improvement in predictive capacity was achieved using multiple
      regression equations developed from measurement of both bones (individual
      fetuses: MAE = 2.6 days; equations including mean values within litters: MAE =
      2.2 days). The results demonstrate that ultrasound can be used to estimate stage
      of pregnancy in prolific ewes, and that the use of mean values for bone
      measurements from different fetuses within litters and/or measurement of bones
      with different growth allometry can increase the reliability of estimates. The
      utility of the procedure depends on the number of fetuses measured per ewe, the
      number of bones measured per fetus and, hence, the time required to measure bones
      and the degree of accuracy required.

PMID- 12051527
TI  - Effects of insulin-like growth factors I and II on tumour-necrosis-factor-alpha
      induced apoptosis in early murine embryos.
AB  - The proposition that members of the insulin-like growth factor superfamily act as
      rescue factors from apoptosis in murine preimplantation embryos was tested. The
      cytokine tumour necrosis factor alpha (TNFalpha) was used to induce apoptosis.
      Zygotes were cultured for 5 days to the blastocyst stage in the presence or
      absence of TNFalpha and in the presence or absence of the insulin-like growth
      factors, IGF-I or IGF-II. Tumour necrosis factor alpha significantly increased
      the percentage of apoptotic cells and reduced the total cell count in Day 5
      blastocysts. When IGF-I or IGF-II were added to the culture medium in the
      presence of TNFalpha, the cell number and apoptotic dead cell index (DCI) were
      restored to control values. Insulin-like growth factor-I alone had a greater
      effect on total cell number than IGF-II alone, but did not significantly decrease
      the apoptotic DCI. In contrast, IGF-II significantly reduced the number of
      apoptotic cells. This study shows that IGFs may play a role as apoptotic survival
      factors in the early mouse embryo.

PMID- 12051528
TI  - Consequences of intrauterine growth restriction on ventilatory and
      thermoregulatory responses to asphyxia and hypercapnia in the newborn guinea-pig.
AB  - The purpose of this study was to determine the effects of prenatal growth
      restriction on the ventilatory and thermoregulatory responses to asphyxia and
      hypercapnia in the newborn guinea-pig. Spontaneously growth-restricted (SGR)
      animals born to unoperated dams, and growth-retarded (GR) neonates born to dams
      in which a uterine artery had been ligated at mid gestation, were studied and
      compared with control neonates. Ventilatory responses to progressive asphyxia and
      steady-state hypercapnia were tested at 3-6 days of age using a barometric
      plethysmograph. The animals were then killed and the brains prepared for
      histological and immunohistochemical analysis. During progressive asphyxia, SGR
      neonates (n = 5) had a significantly increased minute ventilation compared with
      both control (n = 6) and GR (n = 5) neonates. Rectal temperature fell
      significantly in GR and SGR neonates after progressive asphyxia, but was
      unchanged in control neonates. The ventilatory responses to steady-state
      hypercapnia were not different in the GR, SGR and control neonates. The
      immunoreactive expression of glial fibrillary acidic protein, tyrosine
      hydroxylase, substance P and met-enkephalin in the medulla was also not different
      between the three groups. It was concluded that prenatal growth restriction is
      associated with alterations in the respiratory and thermoregulatory responses to
      asphyxia and hypercapnia, with greater effects observed when in utero growth
      restriction arises spontaneously, compared with that produced experimentally over
      approximately the last half of gestation.

PMID- 12051529
TI  - In vitro development of porcine parthenogenetic and cloned embryos: comparison of
      oocyte-activating techniques, various culture systems and nuclear transfer
      methods.
AB  - The present study compares the development of porcine embryos following several
      oocyte activation techniques and culture systems using in-vitro-matured porcine
      oocytes. Two different nuclear transfer techniques (electrofusion and nuclear
      injection) were also tested using adult somatic cell (nucleus) and enucleated
      cytoplasm. In Experiment 1, oocytes activated by electric pulse, electric pulse +
      6-dimethylaminopurine (6-DMAP), or ionomycin + 6-DMAP showed higher pronuclear
      formation rates (P<0.01) than those in the other groups (negative control and
      ionomycin treatment). Of these three groups, oocytes activated by electric pulse
      + 6-DMAP showed greater developmental rate to the blastocyst stage and higher
      cell numbers in blastocysts than those activated by electric pulse or ionomycin +
      6-DMAP (P<0.05). In Experiment 2, activated oocytes were grouped and cultured as
      follows: (i) NCSU-PVA for 6 days (PVA-PVA); (ii) NCSU-BSA for 6 days (BSA-BSA);
      (iii) NCSU-FBS for 6 days (FBS-FBS); (iv) NCSU-PVA for 4 days followed by NCSU
      BSA for 2 days (PVA-BSA); (v) NCSU-PVA for 4 days followed by NCSU-FBS for 2 days
      (PVA-FBS); and (vi) NCSU-BSA for 4 days followed by NCSU-FBS for 2 days (BSA
      FBS). Cleavage rates in all experimental groups were not significantly different,
      but the embryos cultured in PVA-BSA or BSA-BSA showed higher blastocyst formation
      rates than those in other groups (P<0.05). In Experiment 3, the pseudo-pronuclear
      formation rate tended to be higher in the electrofusion group than in piezo
      driven nuclear injection group, but the difference was not statistically
      significant (P=0.12). In addition, there was no significant difference between
      groups in cleavage, blastocyst formation, or the number of cells in blastocysts.
      The results indicate that porcine adult somatic cell nuclear transfer can be
      performed by the nuclear injection technique with a piezo-driven
      micromanipulator. In addition, activation by electrical pulse followed by 6-DMAP
      and in vitro culture in BSA-supplemented medium throughout the culture period was
      found to be the most efficient system for the production of porcine
      parthenogenetic embryos in vitro.

PMID- 12051530
TI  - The emerging role of caspase inhibitors in gastrointestinal cancers.

PMID- 12051531
TI  - Helicobacter pylori seroprevalence in patients with chronic bronchitis.
AB  - BACKGROUND: A high Helicobacter pylori seroprevalence has been found in many
      extragastrointestinal disorders. Moreover, it has been reported that the risk of
      chronic bronchitis may be increased in H. pylori-infected patients. The aim of
      this study was to assess the H. pylori seroprevalence in patients with chronic
      bronchitis. METHODS: We evaluated 144 patients with chronic bronchitis (81 men
      and 63 women, aged 53.2+/-12.7 years) and 120 age and sex-matched control
      subjects. All enrolled subjects (bronchitic patients and controls) underwent an
      enzyme-linked immunosorbent assay (ELISA) IgG serologic test for H. pylori
      diagnosis. RESULTS: A correlation between age and H. pylori IgG level was
      detected for both bronchitic patients (r = 0.42; P = 0.004) and controls (r =
      0.44; P = 0.004). H. pylori seropositivity in the chronic bronchitis group was
      significantly higher than that in controls (83.3% vs 60%; P = 0.007). The mean
      serum concentration of IgG antibodies against H. pylori was also significantly
      higher in patients with chronic bronchitis than in the control subjects (38.7+/
      24.1 U/ml vs 25.9+/-19.3 U/ml; P = 0.02). CONCLUSIONS: Helicobacter pylori
      infection may be associated with chronic bronchitis. Further studies should be
      undertaken to confirm our results and to clarify the potential underlying
      pathogenetic mechanisms.

PMID- 12051532
TI  - Vasoactive intestinal peptide and its relationship to tumor stage in colorectal
      carcinoma: an immunohistochemical study.
AB  - BACKGROUND: Vasoactive intestinal peptide (VIP) is considered to influence
      cellular proliferation through its action on adenylate cyclase. This study
      examined VIP in the tumor-neighboring mucosa (TM) and remote normal mucosa (RM)
      in patients with colorectal carcinoma, and explored its relationship to tumor
      stage. METHODS: Immunohistochemical staining of VIP, using the avidinbiotin
      peroxidase complex technique, was performed on TM and RM from 55 patients,
      surgically resected colorectal carcinomas. The VIP immunoreactivity in the lamina
      propria (LP) of TM and RM was semiquantitatively graded, according to the density
      of VIP immunoreactive fibrous strands, and correlated with clinical
      characteristics, pathological findings, and tumor stage. RESULTS: VIP
      immunoreactivity in the LP of TM and RM was found mainly as fibrous strands, some
      of which were nerve fibers. A few pericryptal myofibroblasts also showed VIP
      immunoreactivity. The VIP immunoreactivity in the LP was significantly greater in
      TM than in RM. The VIP immunoreactivity in the LP of TM was marginally greater in
      lesions with distant metastasis. The VIP immunoreactivity in the LP of RM was
      significantly greater in lesions with deeper wall penetration, in those with
      lymph node metastasis, and in those at more advanced stages. CONCLUSIONS: These
      results suggest a possible trophic role of VIP in the progression of colorectal
      carcinoma, or enhanced VIP secretion secondary to or in parallel with the
      progression of carcinoma.

PMID- 12051533
TI  - Increased expression of tumor necrosis factor-alpha messenger RNA in the
      intestinal mucosa of inflammatory bowel disease, particularly in patients with
      disease in the inactive phase.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), may be involved in the
      pathogenesis of inflammatory bowel diseases (IBDs). The aim of this study was to
      evaluate the effect of TNF-alpha on the inflammatory activity of IBD. METHODS:
      TNF-alpha mRNA expression in intestinal mucosal biopsy specimens from IBD
      patients [ulcerative colitis (UC), n = 54; and Crohn's disease (CD), n = 11] was
      analyzed using a competitive polymerase chain reaction. The degree of macrophage
      infiltration was analyzed by immunohistochemistry, using an antihuman CD68
      antibody. RESULTS: TNF-alpha mRNA expression was increased in UC patients,
      corresponding to the inflammatory activity. However, in CD, TNF-alpha mRNA
      expression was not correlated with the endoscopic findings. CONCLUSIONS: We
      clarified that TNF-alpha mRNA expression was responsible for the inflammatory
      activity in UC. However, TNF-alpha mRNA expression was not correlated with the
      mucosal injury in CD.

PMID- 12051535
TI  - Angioechographic evaluation of tumor thrombi and the effect of transcatheter
      arterial embolization in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Transcatheter arterial embolization (TAE) is considered to be
      relatively ineffective in the treatment of portal and/or hepatic vein tumor
      thrombi associated with hepatocellular carcinoma (HCC). However, we have seen
      patients with a positively enhanced tumor thrombus on angioechography where
      necrosis has occurred after TAE. In this study, we compared the angioechographic
      enhancement of tumor thrombi with the effect of TAE to assess the use of this
      method in predicting the efficacy of TAE, and in predicting survival. METHODS:
      Angioechography, using a small amount of CO2 gas injected into the hepatic
      artery, was performed before TAE in 41 HCC patients with tumor thrombi of the
      portal vein (PVTT; n = 35) or hepatic vein (HVTT; n = 6). The relationship
      between the enhancement of the thrombi and the efficacy of TAE was investigated
      by follow-up ultrasonography. RESULTS: All 13 PVTT that decreased in size had
      shown positive enhancement (PE) before treatment (P < 0.001), while 6 of the 7
      cases (86%) in which the lesions increased in size had shown negative enhancement
      (NE). The survival of patients with PE was significantly longer than that of
      patients with NE (P < 0.005). Multivariate analysis identified two clinical
      variables associated with survival, angioechographic findings of PVTT, and age.
      There were no correlations between enhancement and HVTT. CONCLUSIONS:
      Determination of enhancement of PVTT on angioechography was useful in predicting
      the efficacy of TAE treatment of HCC and the survival time. Angioechography may
      be valuable in treatment decisions for HCC patients with PVTT, especially as a
      guide to the effectiveness of TAE.

PMID- 12051534
TI  - Colorectal carcinoma with special reference to growth pattern classifications:
      clinicopathologic characteristics and genetic changes.
AB  - BACKGROUND: Many colorectal carcinomas are known to develop from preexisting
      polypoid adenomas; however, they can also develop from so-called "flat adenomas".
      To elucidate the growth patterns of flat- or depressed-derived colorectal
      carcinomas, we investigated the clinicopathologic characteristics and genetic
      changes of invasive carcinomas. METHODS: Seventy-five colorectal carcinomas were
      classified into three groups: 46 upward growth (UG) type, 22 downward growth (DG)
      type, and 7 lateral growth (LG) type. All of them had histologically infiltrated
      the submucosa (SM) and muscularis propria (MP). Ki-ras mutation was examined by
      polymerase chain reaction-single-strand conformation polymorphism analysis, and
      overexpression of p53 protein was analyzed by immunohistochemistry. RESULTS: No
      DG or LG carcinomas histologically demonstrated an adenomatous remnant, whereas
      UG carcinomas did (SM, 19 of 26; 73%; MP, 3 of 20; 15%). The percentage of tumors
      existing in the right colon was significantly higher in LG carcinomas (71%) than
      in the UG type (28%; P = 0.037). The frequency of Ki-ras mutation was
      significantly higher in the UG carcinomas than in the DG and LG carcinomas (52%
      vs 0%; P < 0.0001; and vs 0%; P = 0.014). However, the frequency of this mutation
      in SM-UG carcinomas with an adenomatous remnant (9 of 19; 47%) did not differ
      significantly from that in SM-UG carcinomas without an adenomatous remnant (3 of
      7; 43%). The frequency of p53 overexpression did not differ among UG (57%), LG
      (57%), and DG (50%) carcinomas. CONCLUSIONS: These results suggest that UG
      carcinomas develop on the basis of the adenoma-carcinoma sequence, while the
      development of DG and LG carcinomas is different from that of UG carcinomas.

PMID- 12051536
TI  - Extracorporeal shock wave lithotripsy of pancreatic duct stones and patient
      factors related to stone disintegration.
AB  - BACKGROUND: Stones in the main pancreatic duct (MPD) are difficult to remove by
      endoscopic devices alone in some patients who have chronic pancreatitis. We
      treated these patients with extracorporeal shock wave lithotripsy (ESWL) and
      analyzed the patient factors related to disintegration. METHODS: Twenty-four
      patients were treated with ESWL alone or with combined endoscopic-ESWL to
      disintegrate or remove MPD stones. RESULTS: Ten patients were treated by ESWL
      alone and 14 by combined endoscopic-ESWL. A total of 19 patients (79%) were
      effectively treated by either method. The mean MPD diameter decreased
      significantly after ESWL. In most of the patients who had chronic abdominal
      symptoms, these symptoms were relieved at discharge. Severe side effects of
      complications did not occur during ESWL therapy. Acute abdominal symptoms and a
      significant increase in the white blood cell count, total bilirubin, and
      aspartate aminotransferase were observed only immediately after ESWL. Although
      there were no significant differences, we observed that the patients with a
      higher stone disintegration success rate showed the following factors: (1)
      female, (2) non-alcoholic pancreatitis, (3) younger age, (4) shorter duration of
      symptoms, (5) smaller stones, and (6) a lower Hounsfield unit value of stones.
      Although about half of the patients had recurring abdominal symptoms and stones
      during a follow-up period of 12 months, the stones which caused relapse in short
      term intervals were disintegrated easily by ESWL. CONCLUSIONS: We may consider
      the application of ESWL therapies for patients who show the factors associated
      with easily disintegratable stone conditions. These therapies are highly
      effective and relatively safe procedures for pancreatic duct stones in such
      patients.

PMID- 12051537
TI  - Duodenal cancer in a patient with Peutz-Jeghers syndrome: molecular analysis.
AB  - We experienced an unusual case of duodenal adenocarcinoma associated with Peutz
      Jeghers syndrome (PJS). A 34-year-old woman was admitted to our hospital with
      abdominal pain. She had been diagnosed as having PJS at 21 years of age, based on
      the presence of mucocutaneous pigmentation of the lip and fingertips, and colonic
      hamartomatous polyps. Abdominal computed tomography revealed a tumor in the third
      portion of the duodenum extending into the pancreas head. As the tumor was
      pathologically determined to be adenocarcinoma at the time of surgery, pylorus
      preserving pancreaticoduodenectomy was performed. We carried out molecular
      analyses of this patient to examine the pathway of carcinogenesis in PJS. The
      tumor did not show somatic mutation of the APC and K-ras genes, which is a
      critical step for the adenoma-carcinoma sequence in colon cancer. Importantly, a
      germline mutation of the STK11 gene was detected at codon 281 delC in exon 6.
      Moreover, the tumor showed loss of heterozygosity of the 19p marker near STK11
      and somatic mutation of the p53 gene. These findings suggest that STK11 is a
      tumor suppressor gene regulating the development of hamartomas, and that somatic
      mutation of p53 subsequently promotes gastrointestinal cancer at a later stage in
      PJS.

PMID- 12051539
TI  - Metachronous adenocarcinoma occurring at a colostomy site after abdominoperineal
      resection for rectal carcinoma.
AB  - Carcinomas rarely occur at the site of a colostomy. A 73-year-old man underwent
      abdominoperineal resection (Miles' surgical procedure) for rectal carcinoma in
      September 1988. He did not return to the hospital until September 1995, when he
      was admitted with stricture of the stoma. Neither tumor nor ulcer was detected at
      the stoma. The tip of the doctor's little finger was able to pass through the
      stoma, and manual expanding alleviated the stricture. The patient did not return
      to the hospital again until August 1996, at age 81 years, when he visited the
      hospital because of complete stricture of the stoma. A biopsy revealed an
      adenomatous carcinoma, but the results of various examinations suggested no
      metastasis. A portion of the intestine, including the stoma and surrounding skin,
      was resected, and a new stoma was created in the descending colon. We report this
      rare carcinoma occurring at the site of a colostomy, and we review the
      literature.

PMID- 12051538
TI  - Retroperitoneal lymphangioma with a duodenal lesion in an adult.
AB  - A multilocular-cystic and cavernous, retroperitoneal tumor was found in a 40-year
      old man whose past medical history was unremarkable. On admission, he complained
      of a large and still growing intra-abdominal mass associated with dull pain and a
      low-grade fever. Laboratory findings revealed leukocytosis and C-reactive protein
      elevation, compatible with inflammation of the tumor. Percutaneous aspiration of
      the tumor was performed under transabdominal ultrasonographic guidance, and
      continuous drainage of fluid from within the tumor ameliorated his symptoms. From
      preoperative examinations, including radiological imaging, fluid aspiration, and
      endoscopy with biopsy, a diagnosis of retroperitoneal lymphangioma was made.
      Laparotomy revealed extensive adhesions between the tumor and both the duodenum
      and the pancreatic head. A pancreaticoduodenectomy was therefore performed. At 3
      year follow-up, there was no sign of recurrence. Retroperitoneal lymphangioma is
      an uncommon disorder, and the cavernous type is extremely rare. The duodenal
      lesion was an important feature of the present case, and endoscopic biopsy of
      this lesion facilitated precise preoperative diagnosis of retroperitoneal
      lymphangioma.

PMID- 12051540
TI  - Mucinous cystadenoma of the pancreas resected 11 years after cystgastrostomy.
AB  - There have been numerous reports that mucinous cystadenoma of the pancreas can
      transform to mucinous cystadenocarcinoma after cystenterostomy, but few authors
      have reported morphological changes long after cystenterostomy for mucinous
      cystadenoma. A 41-year-old Japanese woman had undergone cystgastrostomy at a
      nearby hospital 11 years before undergoing the treatment reported here. The
      preoperative diagnosis at the time of cystgastrostomy was a pancreatic cyst. At
      laparotomy a cyst, measuring 10cm in diameter, was found in the body and tail of
      the pancreas. The histopathological diagnosis of the cyst wall was mucinous
      cystadenoma of mild dysplasia. Computed tomography 10 years after the
      cystgastrostomy showed that the cyst had decreased in diameter from 10 cm to 5cm.
      Gastroscopy showed a scar at the cystgastrostomy site in the stomach. A complete
      resection of the mucinous cystadenoma was done, 11 years after the
      cystgastrostomy, because of the malignant potential. The resected specimen showed
      mucinous cystadenoma of mild dysplasia with structural and cellular atypia
      similar to that in the previous specimen. There was no malignant change. The
      patient was discharged after an uneventful postoperative course and no recurrence
      has been evident for 6 months to date. This case showed imaging and
      histopathological evidence of the slow-growing nature of mucinous cystadenoma of
      the pancreas.

PMID- 12051541
TI  - The distribution of endocrine cells in the surgically resected stomach.

PMID- 12051542
TI  - A case of early-stage gastric plasmacytoma.

PMID- 12051543
TI  - Linking Helicobacter pylori and chronic bronchitis: fact or fancy?

PMID- 12051544
TI  - Association between morphology and molecular changes in colorectal cancer.

PMID- 12051545
TI  - Who will have the last word?

PMID- 12051546
TI  - The assessment of local tolerance, acute toxicity, and DNA biodistribution
      following particle-mediated delivery of a DNA vaccine to minipigs.
AB  - Particle-mediated DNA delivery was used to administer a DNA vaccine against
      Hepatitis B to minipigs. The study represented one arm of the safety evaluation
      program for this product and was designed to assess local tolerance, acute
      toxicity, and biodistribution of the DNA plasmid. The vaccine was given to 4
      groups of minipigs that were sacrificed at 2, 28, 56, or 141 days after
      treatment. The procedure was well tolerated with mild local skin reactions at 2
      days postdosing and no evidence of systemic toxicity. By 28 days the skin lesions
      had regressed apart from a low grade perivascular mononuclear cell infiltrate in
      the upper dermis, together with a small number of phagocytosed gold particles.
      This infiltrate persisted up to 141 days. The expressed HBsAg was detected by
      immunohistochemistry in keratinocytes (usually in association with an
      intranuclear gold particle) at 2 days but not at later time points. Polymerase
      chain reaction (PCR) was used to assay treatment sites and selected internal
      organs to evaluate biodistribution and persistence of the DNA plasmid. At 2 days
      the plasmid was detected in the treatment sites and also in the inguinal lymph
      nodes. At day 57 it was present in the treatment sites only and by day 141
      appeared to have cleared. The results from this study demonstrate that particle
      mediated gene delivery was well tolerated in the minipig. The biodistribution and
      persistence of the plasmid was within acceptable limits for this type of vaccine.
      As the minipig is regarded as a good model for humans these data support the
      concept that particle-mediated DNA delivery will be safe in human clinical
      applications.

PMID- 12051547
TI  - Olfactory epithelium as a novel toxic target following an intravenous
      administration of vincristine to mice.
AB  - To delineate morphological characteristics of olfactory lesions induced by
      vincristine (VCR), a vinca alkaloid derivative with antitumor activity, male
      BALB/c mice were given a single intravenous injection of 1.95 mg/kg, an estimated
      10% lethal dose (designated as day 1). The animals were serially sacrificed on
      days 2, 3, 5, 10, 15 and 60, and the nasal mucosa was examined
      histopathologically. Cell death was noted in the olfactory epithelia adjacent to
      the respiratory epithelia from days 2 to 5. Inflammatory responses were not
      detected throughout the observation periods. Cell death was identified as
      apoptotic by the terminal deoxyribonucleotidyl transferase-mediated dUTP
      digoxigenin nick-end labeling (TUNEL) assay and electron microscopy. Mitotic
      figures and proliferating cell nuclear antigen (PCNA)-positive reactions were
      diffusely scattered in both the basal and sensory cells. On days 10 or after, no
      prominent histological abnormalities were noted in the olfactory epithelia, which
      suggests the aforementioned lesions were completely recovered. These results
      demonstrate that it is essential to perform histopathological evaluation of the
      nasal mucosa during an early preclinical stage for novel antitumor drugs, since
      olfactory lesions due to the certain compounds like VCR may not be detected by
      any other procedure.

PMID- 12051548
TI  - Skeletal changes in rats given daily subcutaneous injections of recombinant human
      parathyroid hormone (1-34) for 2 years and relevance to human safety.
AB  - Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of
      recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses of 0, 5,
      30, or 75 microg/kg. Treatment caused substantial increases in bone mass
      consistent with the known pharmacologic effects of once-daily administration. As
      determined by quantitative computed tomography (QCT) and histomorphometry, bone
      mass was markedly increased. Substantial new bone formation resulted in a large
      decrease in marrow space accompanied by altered bone architecture. Bone
      proliferative lesions were observed in all PTH( 1-34)-treated groups.
      Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats
      in the 5-, 30-, and 75-microg/kg treatment groups, respectively. Focal osteoblast
      hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the
      specific cellular or molecular mechanisms responsible for the rat bone tumors
      have not been fully elucidated, the data suggest that these lesions resulted from
      the long duration of treatment and the exaggerated pharmacologic response of the
      rat skeleton to daily treatment with PTH(1-34). Important differences between the
      rat study and clinical use in adult humans suggest that the increased incidence
      of bone neoplasia in rats treated for 2 years is likely not predictive of an
      increased risk of bone cancer in skeletally mature adult humans being given PTH(1
      34) for a limited period of time in the treatment of osteoporosis.

PMID- 12051549
TI  - Gastric neuroendocrine tumors in a 2-year oncogenicity study with CD-1 mice.
AB  - Descriptions of two rare gastric neuroendocrine tumors (carcinoids) of
      enterochromaffin (ECL) cells in CD-1 mice (2/50) from a 104-week oncogenicity
      study of a serotonergic/dopaminergic compound are presented. These tumors were
      detected at necropsy and confirmed by histopathology in hematoxylin and eosin-
      and Chromogranin A-stained slides. ECL cell counts of the glandular stomachs were
      determined by quantitative image analysis and did not reveal any hyperplastic
      changes as possible predisposing lesions for carcinoid formation. To investigate
      the possibility of drug-induced hypergastrinemia as the cause of tumor formation
      of ECL cells, gastrin blood levels were measured after treating mice for 7 days
      with the test substance. In this study, Omeprazole, the positive control, raised
      gastrin levels, while the test material did not. It was concluded that these two
      tumors were an example of "late-life"-occurring, spontaneous neuroendocrine
      tumors in the stomachs of aged CD-1 mice.

PMID- 12051550
TI  - Twenty-six-Week carcinogenicity study of chloroform in CB6F1 rasH2-transgenic
      mice.
AB  - The carcinogenic potential of chloroform was evaluated in a short-term
      carcinogenicity testing system using CB6F1 rasH2-Tg (rasH2-Tg) mice. Chloroform
      was administered to rasH2-Tg males at doses of 28, 90, or 140 mg/kg and rasH2-Tg
      females at 24, 90, or 240 mg/kg by oral gavage for 26 weeks. Wild-type (non-Tg)
      male and female mice received doses of 140 mg/kg and 240 mg/kg, respectively. N
      methyl-N-nitrosourea was administered to rasH2-Tg mice by single intraperitoneal
      injection (75 mg/kg) as a positive control. In both the rasH2-Tg and non-Tg mice,
      there was no significant increase in the incidence of neoplastic lesions by
      chloroform treatment. The incidence of hepatocellular foci in the rasH2- and non
      Tg females receiving 240 mg/kg was increased. Forestomach tumors and malignant
      tumors occurred in most of the rasH2-mice in the positive control group. Swelling
      or vacuolation of hepatocytes, a toxic change induced by chloroform, occurred in
      both the rasH2-Tg and non-Tg mice. It is concluded that chloroform, a putative
      human noncarcinogen, did not show evidence of carcinogenic potential in the
      present study using rasH2-Tg mice. This study suggests that the rasH2-Tg mouse
      model may not be appropriate for detecting nongenotoxic carcinogens. However, the
      sensitivity of rasH2-Tg mice to nongenotoxic carcinogens should be assessed with
      consideration of the results from the other ILSI-HESI project studies.

PMID- 12051551
TI  - Acute changes in lung histopathology and bronchoalveolar lavage parameters in
      mice exposed to the choking agent gas phosgene.
AB  - Phosgene (CG) is a highly irritant gas widely used industrially as a chemical
      intermediate for the production of dyes, pesticides, and plastics, and can cause
      life-threatening pulmonary edema within 24 hours of exposure. This study was
      designed to investigate acute changes in lung tissue histopathology and selected
      bronchoalveolar lavage fluid (BALF) factors over time to determine early
      diagnostic indicators of exposure. Three groups of 40 male mice each were exposed
      to 32 mg/m3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were
      exposed to filtered room air for 20 minutes, both exposures were followed by room
      air washout for 5 minutes. At 1, 4.8, 12, 24, 48, and 72 hours after exposure
      each group of mice was euthanized and processed for histopathology,
      bronchoalveolar lavage or gravimetric measurements, respectively. Over time, the
      histopathological lesions were characterized by acute changes consisting of
      alveolar and interstitial edema, fibrin and hemorrhage, followed by significant
      alveolar and interstitial flooding with inflammatory cell infiltrates and
      scattered bronchiolar and terminal airway epithelial degeneration and necrosis.
      From 48 to 72 hours, there was partial resolution of the edema and degenerative
      changes, followed by epithelial and fibroblastic regeneration centered on the
      terminal bronchiolar areas. Bronchoalveolar lavage was processed for cell
      differential counts, LDH, and protein determination. Comparative analysis
      revealed significant increases in both postexposure lung wet/dry weight ratios,
      and early elevations of BALF LDH and protein, and later elevations in leukocytes.
      This article describes the use of histopathology to chronicle the temporal
      pulmonary changes subsequent to whole body exposure to phosgene, and correlate
      these changes with BALF ingredients and postexposure lung wet weights in an
      effort to characterize toxic gas-induced acute lung injury and identify early
      markers of phosgene exposure.

PMID- 12051552
TI  - The effects of methyl methacrylate on nasal cavity, lung, and antioxidant system
      (an experimental inhalation study).
AB  - Methyl methacrylate (MMA) is a monomer, commonly used in neurosurgery, orthopedic
      surgery, and in dental clinics. The adverse effects of this monomer are well
      described in the literature. This study was designed to evaluate the effects of
      MMA on nasal cavity, lung, and antioxidant status. For this purpose, two
      experimental groups of rats were exposed to MMA (at 1,000 ppm, 6 h/day, 5
      days/week for 4 weeks) by inhalation under poor (group A, n = 12) and normal
      ventilation (group B, n = 11) conditions. A control group (group C, n = 10)
      received normal air. Degeneration of olfactory epithelium, bronchopneumonia,
      interstitial pneumonia, hemorrhage, atelectasis, edema, emphysema, and bronchial
      epithelial hyperplasia were observed in groups A and B. Emphysema was the most
      common lesion. Bronchopneumonia with abscesses was only observed in group A.
      Glutathione levels were significantly decreased and malondialdehyde levels were
      significantly increased in group A. No significant difference was observed in
      superoxide dismutase levels between the groups. The data presented indicate that
      before using MMA, adequate protection systems should be in place to prevent
      occupationally related MMA respiratory-tract injuries.

PMID- 12051553
TI  - Neonatal exposure to p-tert-octylphenol causes abnormal expression of estrogen
      receptor alpha and subsequent alteration of cell proliferating activity in the
      developing Donryu rat uterus.
AB  - In the present study, we investigated immunohistochemically the time-course
      alterations in estrogen receptor alpha (ER) expression and cell proliferating
      activity in the developing uteri of Donryu rats exposed neonatally to a high dose
      p-tert-octylphenol (OP), an endocrine disrupting chemical (EDC). OP-treatment (sc
      injections of 100 mg/kg, every other day from postnatal days 1 to 15) induced an
      early and enhanced ER expression in the luminal epithelium compared with age
      matched controls from postnatal day (PND) 10, and increased proliferating cell
      nuclear antigen (PCNA) positive cells up to PND21. At PND28, ER expression in the
      luminal epithelium of the OP-treated group was decreased, in association with
      decline in the luminal epithelial areas. PND14, the second week of life, is
      coincident with the normal time for differentiation when the luminal epithelium
      invaginates into the stroma to form uterine glands. OP-treatment, however,
      delayed and inhibited gland-formation, and suppressed ER expression in the
      invaginated-luminal and glandular epithelium at this time. These results indicate
      that ER expression in these sites is strongly linked with cell proliferating
      activity. In stromal cells, ER was expressed from PND6 in both groups without any
      PCNA positive cells, but significantly lower values were noted in the OP-treated
      group up to PND10. Our immunohistochemical investigation did not reveal any
      abnormalities in expression of the proto-oncogene c-fos, mitotic inhibitor p21,
      or epidermal growth factor antigen, although the apoptotic index in the luminal
      epithelium was slightly increased in the OP-treated group. These results
      demonstrate neonatal effects of a high dose of OP, already detectable at PND10,
      with early and enhanced ER expression, resulting in increase of cell
      proliferative activity in the luminal epithelium, though expression in the
      glandular epithelium was suppressed in relation to inhibited gland-genesis. The
      present study thus suggests that neonatal exposure to high doses of EDCs with
      estrogenic activity can induce abnormal differentiation in the developing rat
      uteri via abnormal ER expression and subsequent alteration of cell proliferating
      activity.

PMID- 12051554
TI  - Alpha-glutathione S-transferase in the assessment of hepatotoxicity--its
      diagnostic utility in comparison with other recognized markers in the Wistar Han
      rat.
AB  - The diagnostic utility of alpha-glutathione S-transferase (alphaGST) in the
      assessment of acute hepatotoxicity was compared with a range of markers including
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Rats were
      given a single oral dose of either alpha-naphthylisothiocynate (AN IT),
      bromobenzene (BrB). or thioacetamide (TAM) at concentrations previously shown to
      induce marked hepatotoxicity. The progression of each hepatic lesion was
      monitored by the measurement of a battery of markers, including alphaGST, in
      plasma collected at time points ranging from 3 h to 7 days after dosing. alphaGST
      was seen to increase significantly at 24 h (ANIT/BrB) and 3 h (TAM) postdosing,
      corresponding with histopathological findings. For each compound, when the degree
      of insult was most severe, fold increases in alphaGST were greater than those
      seen with ALT and AST, yet lower than those seen with glutamate dehydrogenase
      (BrB and ANIT). sorbitol dehydrogenase (TAM), or total bilirubin and bile acids
      (ANIT). Elevations in alphaGST were also detected no earlier than any other
      marker. AlphaGST in the rat was shown to be a valid marker of hepatotoxicity;
      however, its measurement offered no additional information in detecting either
      the time of onset/recovery or the severity of each type of hepatic injury
      induced.

PMID- 12051555
TI  - Air pollution and brain damage.
AB  - Exposure to complex mixtures of air pollutants produces inflammation in the upper
      and lower respiratory tract. Because the nasal cavity is a common portal of
      entry, respiratory and olfactory epithelia are vulnerable targets for
      toxicological damage. This study has evaluated, by light and electron microscopy
      and immunohistochemical expression of nuclear factor-kappa beta (NF-kappaB) and
      inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal
      mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy
      mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly
      polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a
      less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF
      kappaB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks;
      subsequent damage included alterations of the blood-brain barrier (BBB),
      degenerating cortical neurons, apoptotic glial white matter cells, deposition of
      apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and
      pericytes, nonneuritic plaques, and neurofibrillary tangles. Persistent pulmonary
      inflammation and deteriorating olfactory and respiratory barriers may play a role
      in the neuropathology observed in the brains of these highly exposed canines.
      Neurodegenerative disorders such as Alzheimer's may begin early in life with air
      pollutants playing a crucial role.

PMID- 12051556
TI  - Periosteal hyperostosis (exostosis) in DBA/1 male mice.
AB  - Periosteal hyperostosis (exostosis) was identified in 5.9% (11/188) of DBA/1 male
      mice 10-14 weeks old used for collagen-induced arthritis (CIA) efficacy testing
      of immunomodulatory biologics. Mice with and without CIA in the affected limb,
      and also control and treated groups, were involved, with bilateral lesions in one
      mouse. Hyperostosis was characterized by circumferential and raised masses of
      variable location, length, and laterality, generally external to but occasionally
      breaching the periosteum of the metatarsals, metacarpals, tibia, femur, and
      humerus. Proportionally, the hyperostotic foci consisted of cancellous and woven
      bone, followed by osteoid, cartilage, and fibrous connective tissue and rarely
      inflammatory cells. A displaced, presumably pathological fracture with callus
      formation was a concurrent lesion in only one case. Tartrate-resistant acid
      phosphatase-positive cells were frequent at bony interfaces, indicating an active
      resorptive process. Periosteal hyperostosis is an incidental and potentially
      common finding in DBA/1 mice. Underreporting may occur due to the male bias in
      disease expression of this CIA model, sampling bias (generally paws only), tissue
      obliteration in the presence of CIA, and lack of comprehensive historical data on
      the background and aging lesions in this strain of mouse. Identification of such
      confounding bony lesions is important to the interpretation of efficacy studies,
      and suggests the need to further examine the biology of bone development in this
      strain of mouse.

PMID- 12051557
TI  - In vitro models to study hepatotoxicity.
AB  - Drug discovery and development consists of a series of processes starting with
      the demonstration of pharmacological effects in experimental cell and animal
      models and ending with drug safety and efficacy studies in patients. A main
      limitation is often the unacceptable level of toxicity with the liver as the
      primary target organ. Therefore, approaches to study hepatic toxicity in the
      early phase of drug discovery represent an important step towards rational drug
      development. A variety of in vitro liver models have been developed in the past
      years. Next to their use in drug development, they can also be applied to study
      environmental toxins and their hepatotoxicity. The 3 main approaches are ex vivo
      isolated and perfused organ models, precision-cut liver slices and cell culture
      models. Although the advantage of whole organ perfusions is based on the
      assessment of physiologic parameters such as bile production and morphologic
      parameters such as tissue histology, cell culture models can be efficiently used
      to assess cellular metabolism, cytotoxicity and genotoxicity. The advantage of
      precision-cut liver slices is based on the juxtaposition of cellular assays and
      tissue morphology. None of these models can be compared as they all focus on
      different fields of hepatoxicology. For the future, the ideal setup for testing
      the hepatic toxicity of a new compound could of primary studies in cell or slice
      cultures to assess cellular effects and secondary studies using ex vivo perfused
      organs to examine gross organ function parameters and histology.

PMID- 12051558
TI  - An immunohistochemical label to facilitate counting of ovarian follicles.
AB  - U.S. and internationally harmonized Health Effects Test Guidelines for
      Reproduction and Fertility Effects include enumeration of primordial and
      developing ovarian follicles as endpoints of safety tests, and the number of
      these structures is also of interest for other aspects of reproductive biology.
      Performing the counts microscopically on representative hematoxylin and eosin
      (H&E)-stained sections of ovary is tedious and error-prone. The ability to mark
      oocyte nuclei distinctly with an antibody significantly increases speed and
      accuracy of counting. We have identified a rabbit polyclonal antibody directed
      against a synthetic 14-amino acid sequence from human cytochrome P-450 1B1
      (CYP1B1) that unequivocally marks rodent oocyte nuclei, in addition to nuclei of
      some ovarian granulosa and theca cells. Follicles of all degrees of maturity are
      easily distinguished from ovarian background; ability to detect and identify
      primordial follicles is particularly enhanced. High-contrast and high-resolution
      labeling was achieved with routine immunohistochemical procedures using an avidin
      biotin-peroxidase method on rat and mouse tissues fixed in 10% neutral buffered
      formalin.

PMID- 12051559
TI  - Statistical methods for carcinogenicity studies.

PMID- 12051561
TI  - Year's comments for 2001.

PMID- 12051560
TI  - The Society of Toxicologic Pathology's recommendations on statistical analysis of
      rodent carcinogenicity studies.

PMID- 12051562
TI  - The branching order and phylogenetic placement of species from completed
      bacterial genomes, based on conserved indels found in various proteins.
AB  - The presence of shared conserved inserts and deletions (indels or signature
      sequences) in proteins provides a powerful means for understanding the
      evolutionary relationships among the Bacteria. Using such indels, all of the main
      groups within the Bacteria can be defined in clear molecular terms and it has
      become possible to deduce that they branched from a common ancestor in the
      following order: Low G + C gram-positive --> High G+C gram-positive -->
      Deinococcus Thermus --> Cyanobacteria --> Spirochetes --> Aquifex-Chlamydia
      Cytophaga --> Proteobacteria-1 (epsilon, delta) --> Proteobacteria-2 (alpha) -->
      Proteobacteria-3 (beta) --> Proteobacteria -4 (gamma). The usefulness of this
      approach for understanding bacterial phylogeny was examined here using sequence
      data from various completed bacterial genomes. By using 12 indels in highly
      conserved and widely represented proteins, the species from all 41 completed
      bacterial genomes were assigned to different groups; and the observed
      distribution of these indels in different species was then compared with that
      predicted by the signature sequence model. The presence or absence of these
      indels in various proteins in different bacteria followed the pattern exactly as
      predicted: and, in more than 450 observations, no exceptions or contradictions in
      the placement of indels were observed. These results provide strong evidence that
      lateral gene transfer events have not affected the genes containing these indels
      to any significant extent. The phylogenetic placement of bacteria into different
      groups based on signature sequences also showed an excellent correlation with the
      16 S rRNA with 39 of the 41 species assigned to the same group by both methods.
      These results strongly vindicate the usefulness of the signature sequence
      approach to understanding phylogeny within the Bacteria and show that it provides
      a reliable and internally consistent means for the placement of bacterial species
      into different groups and for determining the relative branching order of the
      groups.

PMID- 12051563
TI  - Speciation of termite gut protists: the role of bacterial symbionts.
AB  - At least 12 termite gut protists have been named because of their bacterial
      symbionts. Dozens more species are diagnosed by epi- and endosymbionts and more
      still have regular bacterial associations referred to in their species
      description. Molecular systematic studies have begun to identify these bacteria,
      but the ecological relations with their protist bionts are still unknown. Recent
      findings of acetogenic spirochetes in termite guts may explain the peculiar
      arrangement of spirochetes on some of these protists. Other bacteria function as
      motility or chemotactic symbionts of these protists. The size and shape of the
      parabasal body, a Golgi complex, are morphological characters of the Parabasalia
      (trichomonads, hypermastigids) that may be influenced by regular, heritable epi-
      and endosymbiotic bacteria.

PMID- 12051564
TI  - Susceptibility of motile and cystic forms of Borrelia burgdorferi to ranitidine
      bismuth citrate.
AB  - Gastrointestinal symptoms accompanying Lyme disease have not been considered in
      the treatment of Lyme patients yet. Here we examine the effect of ranitidine
      bismuth citrate (RBC) on motile and cystic forms of Borrelia burgdorferi in
      vitro, to determine whether it could cure this bacterial infection in the
      gastrointestinal tract. When motile forms of B. burgdorferi were exposed to RBC
      for 1 week at 37 degrees C, the minimal bactericidal concentration (MBC) was > 64
      mg/ml. At 30 degrees C, the MBC was > 256 mg/ml. When the incubation lasted for 2
      weeks at 37 degrees C, the MBC dropped to > 2 mg/ml. Bismuth aggregates were
      present on the surface of B. burgdorferi when RBC > or = MBC, as shown by
      transmission electron microscopy (TEM). Cystic forms of B. burgdorferi, exposed
      to RBC for 2 weeks at 37 degrees C, were examined by cultivation in BSK-H medium
      (Sigma B3528). They were stained with acridine orange (pH 6.4, pH 7.4) and
      studied by TEM. The MBC for RBC for young cystic forms (1 day old) and old cysts
      (8 months old) was estimated to be > 0.125 mg/ml and > 2 mg/ml, respectively.
      Bismuth aggregates were attached to the cysts and, in some, the pin-shaped
      aggregates penetrated the cyst wall. The bismuth aggregates also bound strongly
      to blebs and granules of B. burgdorferi when RBC > or = MBC. When B. burgdorferi
      is responsible for gastrointestinal symptoms, bismuth compounds may be candidates
      for eradication of the bacterium from the gastrointestinal tract.

PMID- 12051566
TI  - Global market: shellfish imports as a source of reemerging food-borne hepatitis A
      virus infections in Spain.
AB  - A total of 16 mollusk imports from South America to Spain, including clam and
      scallop species, were analyzed for hepatitis A virus (HAV), due to the great
      concern about this type of food after an important hepatitis A outbreak in
      eastern Spain in September 1999. In addition, clams from the stock that had
      caused the outbreak were also tested. Of the 17 stocks, four were positive for
      the presence of HAV RNA as demonstrated by RT-PCR and Southern hybridization.
      Contradictory analyses confirmed the results of the primary tests in all cases.
      The findings obtained in this work strongly support the role of mollusk imports
      from endemic areas of HAV as an important vehicle of hepatitis A, and demonstrate
      the imperative need for sanitary control measures to prevent future outbreaks of
      this disease.

PMID- 12051565
TI  - Diversity among clinical isolates of penicillin-resistant Streptococcus mitis:
      indication for a PBP1-dependent way to reach high levels of penicillin
      resistance.
AB  - A total of 12 non-epidemiologically related clinical isolates of Streptococcus
      mitis that showed different levels of resistance to penicillin were studied.
      Membrane-protein profiles and penicillin-binding protein (PBP) patterns showed a
      great polymorphism; and patterns of 4-7 PBPs, with sizes that ranged from
      approximately 101 kDa to approximately 40 kDa, were detected in each strain. No
      association could be found between PBP pattern and resistance level to penicillin
      among these isolates. Arbitrarily primed PCR confirmed the genetic diversity
      among this group of streptococci. One of the isolates of intermediate level of
      resistance to penicillin, which showed a PBP pattern similar to that of the high
      resistance strains, was used as a laboratory model to analyse the mechanism
      underlying high-resistance acquisition by these strains. A 14-fold increase in
      penicillin resistance was obtained after a single selection step, which resulted
      in a decrease in penicillin affinity for PBP1. The size of this PBP (92 kDa) and
      the differences in PBP profiles of the penicillin-resistant clinical isolates
      suggest the existence in S. mitis of PBP-mediated mechanisms to acquire high
      level resistance to penicillin, among which alterations in PBP1 seem to play a
      main role, in contrast to the PBP2X mediated mechanism described for other
      streptococci.

PMID- 12051567
TI  - Cyanobacterial diversity in extreme environments in Baja California, Mexico: a
      polyphasic study.
AB  - Cyanobacterial diversity from two geographical areas of Baja California Sur,
      Mexico, were studied: Bahia Concepcion, and Ensenada de Aripez. The sites
      included hypersaline ecosystems, sea bottom, hydrothermal springs, and a shrimp
      farm. In this report we describe four new morphotypes, two are marine epilithic
      from Bahia Concepcion, Dermocarpa sp. and Hyella sp. The third, Geitlerinema sp.,
      occurs in thermal springs and in shrimp ponds, and the fourth, Tychonema sp., is
      from a shrimp pond. The partial sequences of the 16S rRNA genes and the
      phylogenetic relationship of four cyanobacterial strains (Synechococcus cf.
      elongatus, Leptolyngbya cf. thermalis, Leptolyngbya sp., and Geitlerinema sp.)
      are also presented. Polyphasic studies that include the combination of light
      microscopy, cultures and the comparative analysis of 16S rRNA gene sequences
      provide the most powerful approach currently available to establish the diversity
      of these oxygenic photosynthetic microorganisms in culture and in nature.

PMID- 12051568
TI  - Remembering a microbiologist: Alfredo Sordelli (1891-1967).

PMID- 12051569
TI  - Commentary on the report "Competitive capacity of Germany as a location for drug
      research and development--the Boston Consulting Group" November 2001.

PMID- 12051570
TI  - The efficacy of Ginkgo special extract EGb 761 in patients with tinnitus.
AB  - OBJECTIVE: The objective of the present study in 60 patients with chronic
      tinnitus aurium was to confirm the efficacy of oral treatment with 2 x 80 mg
      Ginkgo special extract EGb 761 per day subsequent to 10-day EGb 761 infusion
      treatment. METHODS: Patients with chronic tinnitus aurium underwent 10 days of in
      patient infusion treatment with 200 mg/day EGb 761, after which they were
      randomized to double-blind, oral out-patient treatment with either 2 x 80 mg/day
      EGb 761 or placebo, given over a scheduled treatment period of 12 weeks. The
      primary outcome measure was the change in tinnitus volume in the more severely
      affected ear during randomized treatment. RESULTS: Fifty-two of 60 patients
      (89.7%) completed the infusion treatment; complete sets of data were available
      for 40 (66.7%), 30 (50.0%) and 22 (36.7%) patients after 4, 8 and 12 weeks of
      randomized treatment, respectively. For the primary outcome measure, significant
      superiority of EGb 761 over placebo was demonstrated in the intention-to-treat
      analysis data set after 4, 8 and 12 weeks of out-patient treatment (p < 0.05, 1
      tailed), although the absolute treatment group difference was moderate. The
      results were supported by the secondary outcome measures for efficacy (e.g.
      decreased hearing loss, improved self-assessment of subjective impairment).
      During out-patient treatment, there were no attributable adverse events under EGb
      761. CONCLUSIONS: A combination of infusion therapy followed by oral
      administration of Ginkgo special extract EGb 761 appears to be effective and safe
      in alleviating the symptoms associated with tinnitus aurium.

PMID- 12051571
TI  - Pharmacokinetics of dexloxiglumide after administration of single and repeat oral
      escalating doses in healthy young males.
AB  - OBJECTIVE: To assess the pharmacokinetics, safety and tolerability of
      dexloxiglumide, a new CCK1 receptor antagonist currently under development for
      the treatment of the constipation-predominant irritable bowel syndrome. SUBJECTS
      AND METHODS: Twelve volunteers were enrolled in the present study and received
      orally 100, 200 and 400 mg of dexloxiglumide as tablets as a single dose followed
      by repeated t.i.d. doses for 7 days according to a randomized, double-blind,
      double-dummy complete crossover design. Plasma and urine were collected before
      drug administration and up to 72 h after dosing. Dexloxiglumide plasma and
      urinary concentration, determined using validated HPLC methods with UV detection,
      were used for the pharmacokinetic analysis by standard noncompartmental methods.
      In addition, dexloxiglumide safety and tolerability were evaluated throughout the
      study period by performing standard laboratory tests, by recording vital signs
      and ECGs and by monitoring the occurrence and severity of adverse events.
      RESULTS: After a single oral administration, dexloxiglumide was rapidly
      bioavailable with mean t(max) ranging from 0.9 - 1.6 h at all doses. The mean
      peak plasma concentrations (Cmax) were 1.7+/-0.6, 5.4+/-1.7, and 11.9+/-4.7
      microg/ml, and the mean area under the plasma concentration-time curves (AUC)
      were 4.4+/-3.3, 8.6+/-3.6, and 18.3+/-5.9 microg x h/ml at the 3 doses,
      respectively. Apparent plasma clearance (CL/F) was 30.8+/-13.9, 27.2+/-10.6, and
      21.1+/-8.6 l/h at the 3 doses, respectively. The apparent elimination half-life
      from plasma (t1/2) ranged from 2.6 - 3.3 h at the 3 doses. The excretion of
      unchanged dexloxiglumide in 0 - 72 h urine accounted for approximately 1% of the
      administered dose and this was true for all doses. Dexloxiglumide renal clearance
      (CLR) averaged 0.4+/-0.4, 0.4+/-0.2, and 0.3+/-0.3 l/h for the 3 doses,
      respectively. After the last dose of the repeated dosing period dexloxiglumide
      Cmax occurred at 1.1 - 1.6 h after drug administration and averaged 2.4+/-1.3,
      7.1+/-2.9, and 15.3+/-2.7 microg/ml for the 3 doses, respectively. The AUC values
      averaged 5.9+/-3.0, 16.0+/-8.8, and 50.8+/-38.1 microg x h/ml, respectively. The
      area under the plasma concentration-time curve calculated at steady state within
      a dosing interval (AUCss) averaged 4.6+/-1.6, 11.3+/-3.6, and 28.4+/-8.2 microg x
      h/ml, whereas CL/F averaged 20.3+/-8.3, 16.3+/-9.0, and 10.3+/-5.0 l/h at the 3
      doses, respectively. Dexloxiglumide t1/2 could not be accurately calculated due
      to the high inter-subject variability and to sustained dexloxiglumide plasma
      concentrations that precluded the identification ofthe terminal phase of the
      plasma concentration-time profiles. However, it appeared that dexloxiglumide t1/2
      was considerably prolonged at the dose of 400 mg. CLR averaged 0.4+/-0.4, 0.3+/
      0.3, and 0.3+/-0.1 l/h for the 3 doses, respectively. After a single dose, the
      plasma pharmacokinetics of dexloxiglumide were dose-independent in the dose range
      100 - 400 mg. After repeated dose the pharmacokinetics of dexloxiglumide were
      virtually dose-independent in the dose range 100 - 200 mg. A slight deviation
      from linear pharmacokinetics was found with a dose of 400 mg. Dexloxiglumide
      plasma pharmacokinetics were also time-independent in the dose range 100 - 200 mg
      with a deviation from expectation based on the superimposition principle with a
      dose of 400 mg. Dexloxiglumide urinary excretion and renal clearance were both
      dose- and time-independent in the dose range 100 - 400 mg. The safety and
      tolerability of dexloxiglumide administered to healthy young males was good up to
      the maximum investigated dose of 400 mg both after single and after repeated
      doses. CONCLUSIONS: The safety and pharmacokinetic profile of dexloxiglumide when
      the drug is administered as single and repeated doses in the dose range 100 - 400
      mg provides the rationale for the choice of the treatment schedule (200 mg
      t.i.d.) for the efficacy trials in patients with (constipation-predominant)
      irritable bowel syndrome.

PMID- 12051572
TI  - Methylation of quercetin and fisetin, flavonoids widely distributed in edible
      vegetables, fruits and wine, by human liver.
AB  - The aim of this investigation was to study the methylation of quercetin and
      fisetin, 2 chemically related flavonoids, in human liver and to this purpose, an
      assay was set-up to measure the rates of quercetin and fisetin methylation in
      human liver. The methylation rates (pmol/min/mg) of quercetin and fisetin were
      measured in 10 liver samples and the mean +/- SD and the median were 170+/-30 and
      177 (quercetin) and 183+/-15 and 178 (fisetin). The rates of quercetin and
      fisetin methylation were not different (p = 0.283). The fold of variation among
      samples was 2 (quercetin) and 1.3 (fisetin). Methyltransferase towards quercetin
      and fisetin followed Michaelis-Menten kinetics, and the Km values were 2.6+/-0.3
      (quercetin) and 8.6+/-0.7 microM (fisetin, p = 0.009) and the Vmax values were
      187+/-20 (quercetin) and 276+/-33 pmol/min/mg (fisetin, p = 0.009). Two, 4 and 8
      microl of red Chianti wine added to the incubation mixture reduced the rate of
      quercetin methylation to 75+/-4%, 65+/-9% and 59+/-9%, respectively, and that of
      fisetin methylation to 62+/-3%, 51+/-3% and 44+/-4%, respectively. In conclusion,
      quercetin and fisetin are methylated in human liver and their rates of
      methylation have a limited variation among subjects.

PMID- 12051573
TI  - Nitazoxanide pharmacokinetics and tolerability in man using single ascending oral
      doses.
AB  - OBJECTIVES: Nitazoxanide (N) is a new broad-spectrum intestinal antiparasitic
      agent. Deacetyl-N or tizoxanide (T) and its glucuronide (TG) are the major
      circulating species metabolites after oral administration of N. Bioavailability
      is substantially increased by food. The objectives of this phase IA study were to
      assess the tolerability and to determine the pharmacokinetic linearity of T and
      TG after single oral administration of increasing doses of N with and without
      food in healthy volunteer subjects. METHODS: Thirty-two healthy male volunteers
      were randomly assigned to 1 of 4 treatment groups. In each successive group, 2
      subjects received a placebo and 6 received a single oral dose of 1 g, 2 g, 3 g,
      or 4 g of N, first under fasted conditions and a week later with a standardized
      breakfast. Blood samples were collected during 24 h for plasma determination of T
      and TG. General tolerability, adverse reactions, ECG, vital signs and laboratory
      tests were recorded. RESULTS: Tolerability was good up to the maximum dose of 4
      g. Mild, mostly gastrointestinal side effects were observed and their frequency
      increased significantly with the dose level. No significant changes were noted in
      the ECGs, vital signs and laboratory tests. Plasma concentrations increased
      linearly with the dose from 1 - 4 g, although a trend to increased
      bioavailability was observed at 4 g. Food approximately doubled the
      concentrations of T and TG irrespective of dose. Peak times and apparent half
      lives increased in proportion to the dose. The apparent body clearance for total
      T (T+TG) at the highest dose was only half that at the low dose. TG was
      eliminated more slowly than T. CONCLUSION: Nitazoxanide can be safely
      administered up to 4 g single oral doses, with or without food. The slow
      elimination of TG and the overproportional concentrations at the highest dose can
      be accounted for by solubility- or transport-limited elimination mechanisms
      becoming apparent at the upper dose level.

PMID- 12051575
TI  - Optimizing well-being: the empirical encounter of two traditions.
AB  - Subjective well-being (SWB) is evaluation of life in terms of satisfaction and
      balance between positive and negative affect; psychological well-being (PWB)
      entails perception of engagement with existential challenges of life. The authors
      hypothesized that these research streams are conceptually related but empirically
      distinct and that combinations of them relate differentially to sociodemographics
      and personality. Data are from a national sample of 3,032 Americans aged 25-74.
      Factor analyses confirmed the related-but-distinct status of SWB and PWB. The
      probability of optimal well-being (high SWB and PWB) increased as age, education,
      extraversion, and conscientiousness increased and as neuroticism decreased.
      Compared with adults with higher SWB than PWB. adults with higher PWB than SWB
      were younger, had more education, and showed more openness to experience.

PMID- 12051574
TI  - Nitazoxanide pharmacokinetics and tolerability in man during 7 days dosing with
      0.5 g and 1 g b.i.d.
AB  - OBJECTIVES: Nitazoxanide (N) is a new broad-spectrum intestinal antiparasitic
      agent. Deacetyl-N or tizoxanide (T) and its glucuronide (TG) are the major
      circulating metabolites after oral administration of N. The objectives of this
      phase IB study were to assess the tolerability and to determine the
      phannacokinetics of T and TG after 7 days of 0.5 g and 1 g b.i.d. dosing of N in
      healthy volunteer subjects. METHODS: Sixteen healthy male volunteers were
      randomly assigned to 1 of 2 treatment groups. In each group, 2 subjects received
      a placebo and 6 received a single oral dose of 0.5 or 1 g of N followed by 7 days
      of b.i.d. dosing. Blood samples were collected during the first and last dosing
      intervals for plasma determination of T and TG. General tolerability, adverse
      reactions, ECG, vital signs and laboratory tests were recorded before and during
      treatment days. RESULTS: The 0.5 g b.i.d. dose was well-tolerated with only mild
      adverse events not differing significantly from the placebo. The 1 g b.i.d. dose
      was associated with an increased frequency of gastrointestinal side effects,
      primarily diarrhea and abdominal discomfort. No significant changes were noted in
      the ECGs, vital signs and laboratory tests. At the 0.5 g b.i.d. dose, the
      bioavailability of T and TG was only slightly influenced by repeated
      administration. At the 1 g b.i.d. dose regimen, the extent of bioavailability of
      both T and TG was increased by 50-70%, indicating significant accumulation. Tmax
      was not significantly modified. CONCLUSION: Oral administration of 0.5 g of
      nitazoxanide b.i.d. for 7 days with food in healthy volunteers is well-tolerated
      and is not associated with any significant accumulation of T or TG. A higher 1 g
      dose results in an increased frequency of gastrointestinal discomfort and is
      associated with significant accumulation of T and TG.

PMID- 12051576
TI  - The structure of emotional expressivity: each emotion counts.
AB  - Several models of the dimensionality of emotional expressivity were examined in a
      multitrait-multimethod study. Targets and peer raters completed measures of the
      target's emotional expressivity (Berkeley Expressivity Questionnaire. BEQ; J. J.
      Gross & O. P. John, 1995; and a measure of emotion-specific expression) and the
      Big 5 personality dimensions. The results of structural equation modeling and
      analysis of variance revealed that an emotion-specific model was superior to
      models of valence-specific or unidimensional expressivity. The distinct emotions
      differed in their relations with the dimensions of the 5-factor model. These
      results were corroborated by self- and other reports. Finally, the degree of
      convergence between self- and other ratings differed between emotions,
      demonstrating the multidimensional character of emotional expressivity.

PMID- 12051577
TI  - Selective pressures on the once and future contents of ethnic stereotypes:
      effects of the communicability of traits.
AB  - It is hypothesized that traits that are most likely to be the subject of social
      discourse (i.e., most communicable) are most likely to persist in ethnic
      stereotypes over time and that this effect is moderated by the extent to which an
      ethnic group is the subject of social discourse. Study 1 yielded communicability
      ratings of 76 traits. Study 2 tested the relation between a trait's
      communicability and its presence in stereotypes of 4 Canadian ethnic groups.
      Study 3 tested the relation between a trait's communicability and its persistence
      over time in stereotypes of 8 American ethnic groups. Results supported the
      hypotheses. A communication-based analysis of stereotypes appears helpful in
      predicting persistence and change in the contents of stereotypes of real groups
      in the real world.

PMID- 12051578
TI  - A model of (often mixed) stereotype content: competence and warmth respectively
      follow from perceived status and competition.
AB  - Stereotype research emphasizes systematic processes over seemingly arbitrary
      contents, but content also may prove systematic. On the basis of stereotypes'
      intergroup functions, the stereotype content model hypothesizes that (a) 2
      primary dimensions are competence and warmth, (b) frequent mixed clusters combine
      high warmth with low competence (paternalistic) or high competence with low
      warmth (envious), and (c) distinct emotions (pity, envy, admiration, contempt)
      differentiate the 4 competence-warmth combinations. Stereotypically, (d) status
      predicts high competence, and competition predicts low warmth. Nine varied
      samples rated gender, ethnicity, race, class, age, and disability out-groups.
      Contrary to antipathy models, 2 dimensions mattered, and many stereotypes were
      mixed, either pitying (low competence, high warmth subordinates) or envying (high
      competence, low warmth competitors). Stereotypically, status predicted
      competence, and competition predicted low warmth.

PMID- 12051579
TI  - What's wrong with cross-cultural comparisons of subjective Likert scales?: The
      reference-group effect.
AB  - Social comparison theory maintains that people think about themselves compared
      with similar others. Those in one culture, then, compare themselves with
      different others and standards than do those in another culture, thus potentially
      confounding cross-cultural comparisons. A pilot study and Study 1 demonstrated
      the problematic nature of this reference-group effect: Whereas cultural experts
      agreed that East Asians are more collectivistic than North Americans, cross
      cultural comparisons of trait and attitude measures failed to reveal such a
      pattern. Study 2 found that manipulating reference groups enhanced the expected
      cultural differences, and Study 3 revealed that people from different cultural
      backgrounds within the same country exhibited larger differences than did people
      from different countries. Cross-cultural comparisons using subjective Likert
      scales are compromised because of different reference groups. Possible solutions
      are discussed.

PMID- 12051580
TI  - Guilty by mere association: evaluative conditioning and the spreading attitude
      effect.
AB  - Five experiments investigated the phenomenon that attitude formation is not
      confined to the co-occurrence of an attitudinal object with an evaluated
      experience. The pairing of a target with a (dis)liked person not only affects the
      evaluation of the previously neutral person but spreads to other individuals who
      are (pre)associated with the target (spreading attitude effect). Experiments 1
      and 2 provided evidence for the spreading attitude effect in appetitive as well
      as aversive evaluative conditioning. Experiment 3 showed that the spreading
      attitude effect is a robust phenomenon resistant to extinction. Experiment 4
      demonstrated that attitude spread can be transferred to 2nd-order conditioning.
      Finally, Experiment 5 supports the notion that the spreading attitude effect is
      not dependent on cognitive resources. Implications for social as well as applied
      psychology are discussed.

PMID- 12051581
TI  - Knowledge of partner's ability as a moderator of group motivation gains: an
      exploration of the Kohler discrepancy effect.
AB  - O. Kohler (1926, 1927) found that less able performers tried harder as team
      members under conjunctive task demands (Kohler motivation gain effect) and that
      the greatest gain occurred with moderately discrepant coworker abilities (Kohler
      discrepancy effect). Recent investigations have reproduced Kohler's overall
      motivation gain but not the discrepancy effect. The present research examined
      whether workers' foreknowledge of task abilities--present in Kohler's research,
      absent in contemporary studies--moderates the discrepancy effect. Participants
      worked alone or in 2-person teams under conjunctive task demands. Experiment 1
      manipulated foreknowledge of ability. Experiment 2 manipulated discrepancy: a
      (confederate) teammate performed slightly, moderately, or substantially better.
      Both experiments found (a) overall motivation gains and (b) discrepancy
      moderation under foreknowledge conditions. Implications for understanding group
      motivation gains are discussed.

PMID- 12051582
TI  - The necessities and luxuries of mate preferences: testing the tradeoffs.
AB  - Social exchange and evolutionary models of mate selection incorporate economic
      assumptions but have not considered a key distinction between necessities and
      luxuries. This distinction can clarify an apparent paradox: Status and
      attractiveness, though emphasized by many researchers, are not typically rated
      highly by research participants. Three studies supported the hypothesis that
      women and men first ensure sufficient levels of necessities in potential mates
      before considering many other characteristics rated as more important in prior
      surveys. In Studies 1 and 2, participants designed ideal long-term mates,
      purchasing various characteristics with 3 different budgets. Study 3 used a mate
      screening paradigm and showed that people inquire 1st about hypothesized
      necessities. Physical attractiveness was a necessity to men, status and resources
      were necessities to women, and kindness and intelligence were necessities to
      both.

PMID- 12051583
TI  - Dealing with betrayal in close relationships: does commitment promote
      forgiveness?
AB  - This work complements existing research regarding the forgiveness process by
      highlighting the role of commitment in motivating forgiveness. On the basis of an
      interdependence-theoretic analysis, the authors suggest that (a) victims' self
      oriented reactions to betrayal are antithetical to forgiveness, favoring impulses
      such as grudge and vengeance, and (b) forgiveness rests on prorelationship
      motivation, one cause of which is strong commitment. A priming experiment, a
      cross-sectional survey study, and an interaction record study revealed evidence
      of associations (or causal effects) of commitment with forgiveness. The
      commitment-forgiveness association appeared to rest on intent to persist rather
      than long-term orientation or psychological attachment. In addition, the
      commitment-forgiveness association was mediated by cognitive interpretations of
      betrayal incidents; evidence for mediation by emotional reactions was
      inconsistent.

PMID- 12051584
TI  - Intragroup social influence and intergroup competition.
AB  - Three experiments examined the role of intragroup social influence in intergroup
      competition. In the context of a mutual fate control situation, participants in
      Experiment 1 demonstrated more intergroup competition in the presence than in the
      absence of social support for shared self-interest. Experiment 2 revealed that,
      in the context of a Prisoner's Dilemma Game, this social support effect was
      stronger when noncorrespondence of outcomes between the interacting groups was
      low than when it was high. Results from Experiment 3 were consistent with the
      possibility that the effect of social support is attenuated when
      noncorrespondence of outcomes is high because under these circumstances
      intergroup competition is prescribed by a norm of group interest. The
      implications of these findings for understanding the antecedents of
      interindividual-intergroup discontinuity are discussed.

PMID- 12051585
TI  - Prosocial development in early adulthood: a longitudinal study.
AB  - Consistency of measures of a prosocial personality and prosocial moral judgment
      over time, and the interrelations among them, were examined. Participants and
      friends' reports of prosocial characteristics were obtained at ages 21-22, 23-24,
      and 25-26 years. In addition, participants' prosocial judgment was assessed with
      interviews and with an objective measure of prosocial moral reasoning at several
      ages. Reports of prosocial behavior and empathy-related responding in childhood
      and observations of prosocial behavior in preschool also were obtained. There was
      interindividual consistency in prosocial dispositions, and prosocial dispositions
      in adulthood related to empathy/sympathy and prosocial behavior at much younger
      ages. Interview and objective measures of moral reasoning were substantially
      interrelated in late adolescence/early adulthood and correlated with
      participants' and friends' reports of a prosocial disposition.

PMID- 12051586
TI  - Assessment of peripheral lymphadenopathies: experience at a pediatric hematology
      oncology department in Turkey.
AB  - Since a large variety of disorders may lead to lymph node enlargement determining
      the cause of peripheral lymphadenopathy (LAP) in children can be difficult. This
      retrospective study evaluated 200 children who were admitted to an Oncology
      Hematology department because of lymphadenopathy and aimed to determine the
      clinical and laboratory findings that were valuable for differential diagnosis. A
      specific cause for lymphadenopathy was documented in 93 (46.5%) cases. One
      hundred forty (70%) children were classified as having a benign cause for lymph
      node enlargements. Fourteen (10%) of these cases underwent an excisional lymph
      node biopsy, and histopathological examination showed a reactive hyperplasia.
      Sixty (30%) cases were classified as having a malignant disease-causing
      lymphadenopathy. In terms of differential diagnosis, some associated systemic
      symptoms, physical findings, and laboratory investigations showed significant
      difference between benign and malignant lymphadenopathy groups. The following
      findings were determined as being important to alert the physician about the
      probability of a malignant disorder: location of the lymphadenapathy
      (supraclavicular and posterior auricular), duration of the lymph node enlargement
      (>4 weeks), size of the lymph node (>3 cm), abnormal complete blood cell
      findings, abnormalities in chest X-ray, and abdominal ultrasonography.

PMID- 12051587
TI  - Clinical course of children with immune thrombocytopenic purpura treated with
      intravenous immunoglobulin G or megadose methylprednisolone or observed without
      therapy.
AB  - The authors compared the prognosis in 50 children with acute immune
      thrombocytopenicpurpura (ITP) who received intravenous immunoglobulin G (IVIG),
      megadose methylprednisolone (MDMP), or no therapy. Twenty-six children were
      observed with no therapy, 12 children received IVIG, and 12 children received
      MDMP. The percentage of the patients whose platelet counts increased at a level
      of > 20 x 10(9)/L and > 50 x 10(9)/L at 3 days after starting therapy was
      significantly higher in both IVIG and MDMP groups than in the no therapy group (p
      < .01), but there was no significant difference at 10 and 30 days after
      initiation between the 3 groups (p > .05 in each comparison). This result
      suggested that therapy does not increase the rate of recovery but shortens the
      duration of thrombocytopenia in the first days. Management derision in ITP is
      made on clinical condition rather than on platelet count and no treatment options
      is to be preferred even in the face of mucosal bleeding. If the patient has
      extensive bleeding and the decision is to treat, both IVIG and MDMP are equally
      effective in providing a safe platelet level early on.

PMID- 12051589
TI  - Neutrophil hypersegmentation in children with iron deficiency anemia.
AB  - Neutrophil hypersegmentation (NH) is usually associated with vitamin B12 or folic
      acid deficiency. NH is seen in iron deficiency anemia but there are very few case
      studies about this. Neutrophil hypersegmentation was evaluated in 94 children
      with iron deficiency anemia; 23 healthy children comprised the control group with
      similar ages. NH was found in 76/94 (81%) in the study group and 2/23 (9%) of the
      control group. The difference was statistically significant (p < .01).

PMID- 12051588
TI  - The comparison of antibody response to different hepatitis b vaccines with and
      without pre-S2 antigen in children with cancer.
AB  - Children with cancer are at an increased risk of hepatitis B infection and
      chronic liver disease. Since hepatitis B vaccines containing pre-S2 antigen has
      been recently reported as being more efficient in providing immunization in
      healthy individuals, the authors compared antibody response to pre-S2-containing
      vaccine with no-pre-S2-containing hepatitis B vaccine, when given in double doses
      to 100 children receiving chemotherapy. Patients, aged 1 to 16 years with
      negative HBV serology, were vaccinated with 2 different types of HBV vaccines
      between 1997 and 1999. Group 1 received Gen Hevac B containing pre-S2 (n = 41) in
      a dose of 20 microg for patients younger than 10 years old and 40 microg for
      older patients. Group 2 was vaccinated at the same dose with hepatitis B vaccines
      not containing pre-S2 antigen. All vaccinations were repeated at 0, 1, and 6
      months. Serum samples were drawn for determination of anti-HBs titers at 1, 3, 6,
      and 8 months. After the third dose of vaccine, the seroconversion rate was 72% in
      group 1 and 62% in group 2. The anti-HBs levels were higher in the group
      receiving pre-S2-containing hepatitis B vaccine. However, the difference between
      groups was not statistically significant (p > .05). The administration of pre-S2
      containing hepatitis B vaccines may give a better seroconversion and higher
      antibody response to vaccination in children with cancer. But a further large
      scale study is needed to confirm this finding.

PMID- 12051590
TI  - Two CD34+ stem cells from umbilical cord blood enrichment methods.
AB  - The authors describe the relation between clamping time and blood volume
      collected, and two enrichment systems of CD34+ stem cells from umbilical cord
      blood, to determine an excellent recovery with high proliferate ability and bone
      marrow reconstitution. After an obstetrician-based cord blood collection, the
      purification of stem cells was performed either with a combination of monoclonal
      antibodies (negative selections) using the Stem Sep method, or with a positive
      cells selection thanks to their surface CD34 antigens, using the Mini Macs
      system. An excellent recovery of hematopoietic progenitors, burst-forming unit
      erythroid, colony-forming unit granulocyte and macrophage, and colony-forming
      unit granulocyte, erythroid, monocyte, and macrophage, inversely related to the
      rising of clamping time, was performed with the Mini Macs system (54% of
      colonies, with a 90% purity), while with Stem Sep method, hematopoietic
      progenitor recovery was 35% (with an 80% purity). By applying early clamping of
      the umbilical cord blood a greater number of CD34+ cells was obtained and their
      clonogenic activity increased with enrichment. This is particularly useful,
      considering that the number of CD34+ stem cells contained in a unit of placental
      blood is enough for transplanting to a child, but not for an adult engraftment.
      Thus, using this method, a larger number of CD34+ stem cells can be obtained,
      which increases the possibility to reduce graft versus host disease also in adult
      patients, producing survival rates similar to the ones obtained with
      transplantation of bone marrow from unrelated donors.

PMID- 12051591
TI  - Acute suppurative thyroiditis as a rare complication of aggressive chemotherapy
      in children with acute myelogeneous leukemia.
AB  - Acute suppurative thyroiditis (AST) is quite rare, even in immunocompromised
      patients. The authors describe 2 cases of AST during aggressive chemotherapy for
      acute myelogeneous leukemia (AML). They were treated with aggressive combination
      chemotherapy and achieved complete remission. After several courses of
      chemotherapy, they developed fever and pain in the region of the thyroid gland.
      Laboratory tests showed hyperthyroidism and elevated levels of thyroglobulin and
      C-reactive protein. Ultrasonography revealed hypoechoic areas in the thyroid
      gland. A diagnosis of AST was made. Bacterial infections were suspected because
      they were sucessfully treated with antibiotics. After a month, the patients'
      thyroid function and thyroglobulin levels returned to normal without a period of
      transient hypothyroidism. A pyriform sinus fistula was not demonstrated. The
      results suggest that neutropenia and preceding cellulitis around the thyroid
      gland, which might be subsequent to oral mucosal damage induced by anticancer
      drugs, may play a role in the development of AST. AST should be considered a
      potential complication of aggressive chemotheragy for leukemia.

PMID- 12051593
TI  - Polycythemia vera in a 12-year-old girl: a case report.
AB  - A case of a 12-year-old girl presenting with headache and splenomegaly and
      fulfilling the diagnostic criteria of polycythemia vera is reported. Her
      peripheral blood values were as follows: hemoglobin 18 g/dL, red blood cells
      7,000,000/mm3, while blood cells 22,000/mm, and platelets 1,248,000/mm3.
      Phlebotomy was performed initially but was ineffective. Afterward 100 mg/kg per
      day aspirin and 30/mg/kg per day hydroxyurea were given. The patient has been
      asypmtomatic for 1 year and her recent hemoglobin level is 15.5 g/dL, platelet
      count 922,000/mm3, and white blood cell 12,800/mm3. Polycythemia vera is an
      extremely uncommon disease in childhood and for this reason its treatment is not
      well established.

PMID- 12051592
TI  - BK virus-associated fatal renal failure following late-onset hemorrhagic cystitis
      in an unrelated bone marrow transplantation.
AB  - The human polyomavirus BK (BKV)-associated hemorrhagic cystitis (HC) has been a
      frequent and, seldom life-threatening complication after bone marrow
      transplantation (BMT). The authors report a male with melodysplastic syndrome,
      who developed BKV-associated late-onset HC 12 days after HLA-matched unrelated
      BMT. His urine contained epithelial cells with intranuclear inclusion bodies
      suggestive of BKV infection and was positive for BKV in polymerase chain
      reaction. He did not respond to any treatment for HC. In addition, he developed
      BKV-associated acute renal failure on day 26, followed by hepatic veno-occlusive
      disease on day 42. This is the first case in which BKV may be associated with
      fatal progressive renal failure.

PMID- 12051594
TI  - Second transplant for a thalassemia patient after graft rejection: with
      immunosuppression and allogeneic peripheral blood stem cell.
AB  - A 13-year old girl suffering from beta-thalassaemia major received bone marrow
      transplantation (BMT) from her HLA identical bother. After initial engraftment,
      she developed mixed chimerism. Secondary graft rejection occurred at 10 months
      after BMT and resulted in marrow aplasia. A second transplant with the same bone
      marrow donor was performed. The patient was conditioned with antithymocyte
      globulin 90 mg/kg followed by peripheral blood stem cell infusion. There was
      prompt engraftment and patient reverted to complete chimerism. There were no
      severe treatment-related complications or acute or chronic graft versus host
      disease after second transplant. The patient remained transfusion independent at
      26 months after second transplant.

PMID- 12051595
TI  - Central precocious puberty in multisystem Langerhans cell histiocytosis: a case
      report.
AB  - The authors describe a girl with multisystem Langerhans cell histiocytosis (LCH)
      who developed central precocious puberty (CPP). At the age of 19 months she
      presented with otorrhea and polypoid formations in the ear canal; polyps were
      removed and LCH suspected. She subsequently developed diabetes insipidus with a
      documented lesion of the pituitary stalk; she received chemotherapy and began
      therapy with l-desamino-8-D-argininevasopressin. Growth hormone deficiency was
      diagnosed at the age of 4.4 years and GH replacement therapy started. The patient
      has been off therapy for LCH since the age of 6. Signs of pubertal development
      appeared at 7.5 years (bone age 8 years) and gonadotropin-releasing hormone
      analog (GnRHa) treatment was started. During the observation period she developed
      central hypothyroidism. Development of CPP during LCH is extremely rare; to the
      authors 'knowledge, no patient has been described so far. The authors believe
      that CPP was secondary to LCH and did not represent a casual finding, even in the
      absence of hypothalamic-pituitary axis involvement. The presence of preceding
      lesions producing excessive cytokine levels, with damage on the neurosecretory
      apparatus that inhibits the GnRH pulse generator, represents the most intriguing
      hypothesis. The possibility of CPP development should be considered during the
      follow-up of these patients.

PMID- 12051596
TI  - Acute lymphoblastic leukemia presenting as cyclic neutropenia.
AB  - Clinical and laboratory parameters usually allow an easy diagnosis of acute
      lymphoblastic leukemia in most cases. Difficult arises, however, when
      presentation is atypical. A young child with membranous tonsillo-pharyngitis
      secondary to an isolated neutropenia is reported. The neutrophilic count later
      showed fluctuations reminiscent of cylic neutropenia. Bone marrow examination
      revealed the true nature of underlying disorder.

PMID- 12051597
TI  - Coexistence of sickle cell trait and fanconi anemia in a child.

PMID- 12051598
TI  - Serological investigations on Babesia orientalis infection. Status of water
      buffaloes in Hubei Province.
AB  - A total of 230 water buffaloes were sampled for the determination of the
      epidemiological situation of Babesia orientalis infection in Hubei Province,
      using the latex agglutination test. This serological test revealed that 74.7% of
      the collected sera were positive for antibodies against B. orientalis in endemic
      areas. In contrast, only 1.79% of water buffaloes were positive in non-epidemic
      areas. The incidence of the infection was substantially higher in older than in
      younger animals. The results were analysed using mathematical model and indicated
      that these areas were in a stable situation.

PMID- 12051599
TI  - Description of a new Babesia sp. infective for cattle in China.
AB  - A Babesia species has been identified and shown to be transmitted by Hyalomma
      anatolicum anatolicum in China. When larvae, nymphs and adults developed from
      engorged females H. a. anatolicum collected from cattle in Xinjiang province were
      infested onto the Babesia-free calves, piroplasms of Babesia sp. were seen in
      blood smears from cattle infested with nymphs (2 calves), but not from the calves
      infested with larvae (1 calf or adult ticks (2 calves). This Babesia sp. proved
      to be of low virulence, causing 3% parasites which lasted 3-4 days.

PMID- 12051600
TI  - Isolation and preliminary characterization of a large Babesia sp. from sheep and
      goats in the eastern part of Gansu Province, China.
AB  - Two species of Babesia were isolated from naturally infected sheep in the eastern
      part of Gansu province. One of the species was identified as B. ovis, while the
      another one seems as yet to be an unidentified Babesia species. The latter could
      be transmitted transovarially by Haemaphysalis longicornis. It was shown that
      larvae and nymphs transmit the organism to sheep and goats with a prepatent
      period of 5-28 days. As the carrier period of B. ovis is longer than that of the
      larger species and the prepatent period of the larger Babesia is shorter than
      that of B. ovis, it was possible to isolate the unidentified larger species. The
      larger Babesia is polymorphic, including double pyriform, single pyriform, ring
      form, rod-like, three-leafed and budding forms. The size of typical paired
      pyriforms was 1.8-2.5 microm x 0.9-1.8 microm, with mean dimensions of 2.21 +/-
      0.12 microm x 1.17 +/- 0.18 microm. The parasite causes a severe course of
      infection associated with a parasitaemia as high as 23.7% and with a high
      mortality rate in both sheep and goats, being very marked in lambs and imported
      small ruminants.

PMID- 12051601
TI  - Transmission of Babesia sp to sheep with field-collected Haemaphysalis
      qinghaiensis.
AB  - Haemaphysalis qinghaiensis ticks collected in the Gannan Tibet Autonomous Region
      were infested onto a sheep from a Babesia-free area. A strain of small Babesia
      (1.8-2.1 microm in length) was isolated from the sheep. Most of the Babesia in
      erythrocytes were round, oval, single pyriform, double pyriform, budding or
      elongated in form. Measurements were made of 100 single sides of the double
      pyriform Babesia and compared with those for B. motasi and B. ovis from Holland,
      using Student's t-test. The Gannan small Babesia was similar to the B. ovis from
      Holland, but differed significantly from the Dutch B. motasi.

PMID- 12051602
TI  - Transmission of an unidentified Theileria species to small ruminants by
      Haemaphysalis qinghaiensis ticks collected in the field.
AB  - The transmission of a recently identified Theileria species pathogenic for sheep
      and goats in northern China is described. Haemaphysalis qinghaiensis nymphs which
      had been collected from grass in epidemic areas were able to transmit this
      Theileria species to sheep. The pathogen was also transmitted to sheep and goats
      by three batches of adult ticks collected from grass, ticks collected when moving
      about on sheep and ticks which were found partially engorged on sheep or goats.

PMID- 12051603
TI  - The phylogenetic position of the Theileria buffeli group in relation to other
      Theileria species.
AB  - Theileria parasites known as either T. buffeli, T. orientalis or T. sergenti
      share many characteristics and are referred to as the T. buffeli group. The 18S
      ribosomal RNA and merozoite-piroplasm surface protein-encoding genes display a
      wider genetic variation within the T. buffeli group than between well defined
      species like T. annulata and T. parva. Analysis of 18S rRNA gene sequences from
      the database showed that similar groups of related Theileria parasites occur in
      wild ruminants in Japan and the USA. Moreover, a recently discovered Theileria
      species pathogenic for small ruminants in China is phylogenetically related to
      these Japanese Theileria parasites. Phylogenetic analysis of all Theileria 18S
      rRNA genes reported thus far allowed a subdivision into eight clusters. Some of
      these clusters contain multiple different species, whereas others appear to
      contain parasites with similar biological properties whose true speciation
      remains at present unresolved. The consequences for 18S rRNA based diagnostic
      assays is discussed.

PMID- 12051604
TI  - Molecular phylogenetic study of Theileria sp. (Thung Song) based on the
      thymidylate synthetase gene.
AB  - Theileria type Thung Song is an indigenous hemoparasite of dairy cattle from the
      south of Thailand. It has previously been classified using the analysis of a
      comparative set of small subunit ribosomal RNA nucleotide sequences. However, the
      classification of this parasite is still questionable since the Theileria type
      Thung Song was located as the intermediate parasite between pathogenic and benign
      groups. We use the thymidylate synthetase gene (TS) as an alternative for the
      rapid molecular phylogenetic tree construction of benign Theileria type Thung
      Song, Theileria sergenti and Theileria buffeli with Babesia bovis as an out
      group. The partial nucleotide sequences were determined using PCR, cloning and
      dideoxy sequencing. The TS nucleotide sequence data were aligned and analyzed by
      distance and maximum likelihood methods to construct the phylogenetic trees.
      Bootstrap analysis was used to test the strength of the different phylogenetic
      reconstructions. All tree-building methods gave similar results. This study shows
      that T. sergenti and T. buffeli are closely related whereas Theileria type Thung
      Song is more distantly related.

PMID- 12051605
TI  - Epidemiology of ovine theileriosis in Ganan region, Gansu Province, China.
AB  - The epidemiology of ovine theilreiosis in Gannan Tibet Autonomous Region was
      investigated. The results of these studies indicate that this disease is endemic
      in the following counties of Gannan where the vector tick was identified as
      Haemaphysalis qighaiensis: Luqu, Xiahe, Hezuo, Zhuoni, Lintan, Diebu, Maqu. The
      disease mainly occurred from March to May and some cases also occurred in
      September and October. The incidence rates in lambs of sheep brought from areas
      free of the disease were high. On average, the incidence and mortality rates were
      60.8% and 81.5% respectively. In adult sheep, the incidence and mortality rates
      were 17.12% and 65.78% respectively. The mean incidence rate of young goats was
      40% and the mortality was 85.71%. The incidence rate for adult goats was 8.06%
      and the mortality was 73.33%. During the carrier period, the infection rates of
      lambs, young goats, adult sheep and adult goats were 91.7%, 64.29%, 63.13%,and
      20% respectively.

PMID- 12051607
TI  - Immunosensors for diagnostic applications.
AB  - Immunosensors can play an important role in the improvement of veterinary
      diagnostics in areas such as the diagnosis of diseases, drug detection and food
      quality control, by providing applications with rapid detection, high sensitivity
      and specificity. Associated with advances in biochemistry, biotechnology,
      electronics and microfabrication, new transduction devices that translate a
      biological interaction into an electrical signal have been developed. An overview
      of the current immunoassay techniques used in standard diagnosis is presented.
      This includes a brief description of the different immunosensor transducer
      principles and some examples of present and future developments.

PMID- 12051606
TI  - Culture-derived Babesia orientalis exoantigens used as a vaccine against buffalo
      babesiosis.
AB  - Buffalo babesiosis represents a major problem for the livestock industry in
      China. The pathogen of this disease was isolated and identified as Babesia
      orientalis and subsequently propagated in vitro, using the microaerophilus
      stationary phase culture system. The aim of this study was to determine the
      efficacy of exoantigens derived from B. orientalis cultures to induce a
      protective immunity against challenge exposure to virulent organisms in
      laboratory and field. The results showed that exoantigens of B. orientalis could
      induce a high degree of protection against challenge with a virulent B.
      orientalis strain. The animals in the vaccinated group exhibited a slight
      decrease in haemoglobin levels and blood cell counts, whereas animals in the
      control group showed typical clinical symptoms and died between days 11 and 16
      after challenge. In another approach, 82 buffaloes kept in B. orientalis-endemic
      areas were injected with exoantigens plus Freund's adjuvant in two doses at an
      interval of 2 weeks, one month before the endemic period. An additional 86
      buffaloes served as unvaccinated controls. During the endemic period, the
      clinical signs of all buffaloes were monitored and the antibody response was
      investigated, using the latex agglutination test. During the endemic period, none
      of the vaccinated buffaloes showed clinical signs or died, whereas five control
      buffaloes showed clinical signs and two of them died. The mean antibody titre of
      vaccinated animals was higher than that of the control animals. These results
      showed that the culture-derived exoantigens of B. orientalis could be used as a
      vaccine to prevent buffalo babesiosis.

PMID- 12051608
TI  - In vitro cultivation of Chinese strains of Babesia spp.
AB  - Microaerophilus stationary phase culture techniques were applied for the
      continuous cultivation of two Chinese strains of Babesia bovis and B. bigemina,
      to determine the efficacy of antibabesial drugs. The efficacy of chloroquine
      phosphate was 25 times higher than that of berenil. Primaquine phosphate only
      partially reduced the parasitaemia. The results show that Chinese Babesia strains
      can be cultivated in vitro and that this culture system is useful for the
      screening of antibabesial drugs.

PMID- 12051609
TI  - A field test on the treatment of ovine theileriosis with an injection of
      Kangjiaoming.
AB  - A compound effective for the treatment of ovine theileriosis was selected and a
      slow-release preparation (named Kangjiaoming) was prepared. A total of 1,172
      sheep and goats in Zhangjiachuan, Lintan and Yuzhong Counties, Gansu Province,
      where small ruminants are seriously affected by theileriosis, were injected with
      this preparation at a dosage of 5 mg/kg body weight. The infection rate of the
      control group in each of the above-mentioned counties was 98.5%, 85% and 80%,
      respectively. None of the treated animals became sick due to theileriosis. This
      drug proved to be useful for the treatment of carrier cases, although its effect
      was apparently slower than in acute theileriosis. The effect of the preparation
      on some weak animals was not satisfactory.

PMID- 12051611
TI  - The role of cytokines in immunity and immunopathogenesis of pirolasmoses.
AB  - Cells involved in innate and adapted immunity produce cytokines capable of
      orchestrating the immune response to Babesia and Theileria infections. Thus, CD4
      postive T cells recognise peptide fragments of the parasites in the context of
      the major histocompatibility complex (MHC) class II antigen and produce gamma
      interferon (IFN-gamma) to activate macrophages for enhanced phagocytosis and
      intracellular killing of the parasites. In addition, CD4-positive T cells produce
      interleukin 2 (IL-2) which is essential for the clonal expansion of CD8-positive
      T cells. The latter cells kill Theileria-infected host leucocytes in an MHC class
      I-dependent manner. On the other hand, the overproduction of proinflammatory
      cytokines contributes to disease progress.

PMID- 12051610
TI  - Prime-boost: the way forward for recombinant vaccines against apicomplexan
      parasites. A Theileria perspective.
AB  - A good CD8+ response is required for immunity to many intracellular pathogens.
      Traditional antigen delivery using isolated sub-units or killed pathogens and
      adjuvant stimulates strong antibody responses but weak T-cell reactivity.
      Attenuated vaccines are usually more effective. The prime-boost delivery system
      based on immunisation with a naked DNA antigen-gene construct followed by
      boosting with an attenuated vaccinia virus expressing the same antigen is proving
      to be a powerful way to stimulate antigen-specific CD8 responses. Success using
      single epitopes is possible in malaria and we believe this approach holds much
      promise for other apicomplexan parasites such as Theileria spp.

PMID- 12051612
TI  - Ticks and tick-borne diseases in Asia with special emphasis on China.
AB  - An international conference on the control of ticks and tick-borne diseases
      sponsored by the European Commission was held in Shanghai between 11 and 15
      September 2000. Participants from China, Europe, Australia, India, Iran, Israel,
      Japan and Thailand attended the meeting. The main objectives were: (1)
      determining the current situation concerning the epidemiology, economics,
      diagnosis and integrated control measures of ticks and tick-borne diseases caused
      by protozoan and rickettsial pathogens; (2) the creation of regional and
      international research networks and priority settings; (3) the creation of
      training possibilities for young scientists; (4) the identification of new
      research directions and priority settings in relation to vaccine development and
      diagnostics. The papers presented during this meeting focused on parasite
      characterisation and the description of yet unidentified Theileria and Babesia
      species pathogenic for large and small ruminants in China. In addition, progress
      made in immunity and vaccine development against the pathogens mentioned above
      and their vector ticks was also discussed.

PMID- 12051613
TI  - Development of an enzyme-linked immunosorbent assay for the diagnosis of
      Theileria sp. infection in sheep.
AB  - A rapid, sensitive and specific diagnostic method, an enzyme-linked immunosorbent
      assay (ELISA), was developed for the diagnosis of Theileria sp. infection in
      sheep; and optimal conditions were established, such as antigen concentration,
      serum dilution, coating time, Tween-20 concentration and conjugate. The results
      were analyzed by measuring the coefficient of variation (CV). Three sera titers
      (high, middle, low) were analyzed over the measurement range, resulting in a CV
      of around 10%, whereas a 30% variation is the maximum acceptable. The cut-off
      value was determined by the mean of a negative control plus three standard
      deviations. Cross-reaction was found only with Babesia ovis. However, this result
      may be questionable, because it cannot be excluded that these sheep were already
      infected with both Theileria sp. and B. ovis. The ELISA described in the present
      study proved to be a useful tool for studying the epidemiology of Theileria sp.

PMID- 12051614
TI  - The cytoskeleton under external fluid mechanical forces: hemodynamic forces
      acting on the endothelium.
AB  - The endothelium, a single layer of cells that lines all blood vessels, is the
      focus of intense interest in biomechanics because it is the principal recipient
      of hemodynamic shear stress. In arteries, shear stress has been demonstrated to
      regulate both acute vasoregulation and chronic adaptive vessel remodeling and is
      strongly implicated in the localization of atherosclerotic lesions. Thus,
      endothelial biomechanics and the associated mechanotransduction of shear stress
      are of great importance in vascular physiology and pathology. Here we discuss the
      important role of the cytoskeleton in a decentralization model of endothelial
      mechanotransduction. In particular, recent studies of four-dimensional
      cytoskeletal motion in living cells under external fluid mechanical forces are
      summarized together with new data on the spatial distribution of cytoskeletal
      strain. These quantitative studies strongly support the decentralized
      distribution of luminally imposed forces throughout the endothelial cell.

PMID- 12051615
TI  - Regulation of endothelial cell proliferation and apoptosis by cyclic pressure.
AB  - The present study investigated the proliferative and apoptotic responses of human
      umbilical vein endothelial cells (HUVECs) to well-defined, sinusoidal pressures
      (60/20, 100/60, and 140/100 mm Hg/mm Hg) at 1 Hz for up to 24 h under Media 199
      containing either 1% FBS and 0.04% bovine brain extract (BBE) (low serum/growth
      factor conditions) or 10% FBS and 0.4% BBE (normal serum/growth factor
      conditions). Controls were HUVEC maintained under 0.2 mm Hg sustained pressure,
      but otherwise, similar experimental conditions. Under low serum/growth factor
      conditions, exposure of HUVEC to 60/20 mm Hg/mm Hg cyclic pressure at 1 Hz for
      time periods up to 24 h resulted in increases in total cell population density,
      apoptosis, and DNA synthesis. Under normal serum/growth factor conditions,
      exposure of HUVEC to either 60/20 or 100/60 mm Hg/mm Hg cyclic pressures resulted
      in increased DNA synthesis but did not significantly affect cell density or the
      apoptotic index. A reduced rate of cell death was observed in HUVEC under low
      serum/growth factor conditions after exposure to 140/100 mm Hg/mm Hg. Under
      normal serum/growth factor conditions. HUVEC exposed to 140/100 mm Hg/mm Hg
      cyclic pressure exhibited reduced DNA synthesis. Endothelial cells. therefore,
      sense and respond to physiologic levels of cyclic pressure by modifying cell
      proliferation and apoptosis in a mean-pressure-selective manner.

PMID- 12051616
TI  - Measuring receptor/ligand interaction at the single-bond level: experimental and
      interpretative issues.
AB  - There is increased interest in measuring kinetic rates, lifetimes, and rupture
      forces of single receptor/ligand bonds. Valuable insights have been obtained from
      previous experiments attempting such measurements. However, it remains difficult
      to know with sufficient certainty that single bonds were indeed measured. Using
      exemplifying data, evidence supporting single-bond observation is examined and
      caveats in the experimental design and data interpretation are identified.
      Critical issues preventing definitive proof and disproof of single-bond
      observation include complex binding schemes, multimeric interactions, clustering,
      and heterogeneous surfaces. It is concluded that no single criterion is
      sufficient to ensure that single bonds are actually observed. However, a
      cumulative body of evidence may provide reasonable confidence.

PMID- 12051617
TI  - Leukocyte adhesion dynamics in shear flow.
AB  - Of the white blood cells that traverse the circulation, the polymorphonuclear
      leukocytes commonly called neutrophils, are the most numerous, numbering
      approximately 5000 per microliter of blood. In a sense, these cells are the
      emergency response unit within the body's circulatory highway since they are the
      first to be recruited at sites of tissue trauma, infection, or inflammation. The
      chief function of neutrophils is the capture, phagocytosis, and degradation of
      foreign invaders. To carry out this critical function, neutrophils sense
      infection via chemotactic receptors that trigger cellular activation upon
      ligation of as few as 10-100 bacterial or chemokine peptides. Despite this acute
      sensitivity to stimuli, neutrophils circulate in healthy individuals largely in a
      passive state, with a very low efficiency of capture and arrest on quiescent
      endothelium. Here, we define the efficiency as the fraction of all cells passing
      by a given length of vessel wall that is captured and achieves firm adhesion.
      Within seconds of chemotactic signaling, adhesion molecules expressed on the
      plasma membrane of neutrophils are activated and a rapid boost in the efficiency
      of stable adhesion is detected. This occurs for both homotypic neutrophil
      neutrophil adhesion and neutrophil capture and adhesion on inflamed endothelium.
      With such large numbers of circulating neutrophils, and with their inherent
      capability to rapidly adhere to postcapillary venular endothelium, the body has
      evolved a diverse set of mechanisms to regulate the inflammatory cascade that
      begins with intracellular signaling and leads to cell arrest and extravasation at
      sites of tissue insult. In this article we will focus on the interplay between
      particle-fluid dynamics that involve the shear and normal forces that transport
      cells transversely and axially within the vessel, and the activation and
      interaction of adhesion molecules that involve receptor-ligand bond formation
      that enables the neutrophils to resist wall shear stress and adhere to specific
      sites of inflammation.

PMID- 12051618
TI  - Control of fluid shear response in circulating leukocytes by integrins.
AB  - Recent evidence shows that circulating leukocytes respond not only to humoral
      inflammatory mediators but also to fluid stresses. Application of fluid shear
      stress (of the order of 1-10 dyn/cm2) to fresh migrating leukocytes leads to
      initial retraction of pseudopods, an important step to facilitate normal passage
      of leukocytes through the microcirculation and to prevent spreading on the
      endothelium. The ability to respond to fluid shear stress, however, may be
      regulated under different physiological conditions. In the current study, we
      examine the role of integrins in the fluid shear response as measured by
      pseudopod retraction with the use of antibodies against human neutrophil beta1
      and beta2 integrins. Neutrophils adhering via beta2 integrins exhibit normal
      ability to project pseudopods and to migrate. Such cells show normal response to
      fluid shear with rapid pseudopod retraction. In contrast, attachment via beta1
      integrins leads to firmly adhesive leukocytes, spreading and almost no cell
      migration. Such leukocytes exhibit a significantly attenuated ability for
      pseudopod retraction under fluid shear. These results suggest that integrins may
      serve as a regulating mechanism for fluid shear response in human leukocytes.
      Attachment via beta1 integrins may lead to an abolishment of the fluid shear
      response.

PMID- 12051619
TI  - In vitro characterization and micromechanics of tumor cell chemotactic
      protrusion, locomotion, and extravasation.
AB  - The objective of this paper is to introduce some novel in vitro applications in
      characterizing human melanoma cell protrusion and migration in response to
      soluble extracellular matrix protein stimulation. Specifically, we describe two
      assay systems: (1) dual-micropipette manipulation and (2) flow-migration chamber.
      Applications of the dual-micropipet technique provided kinetic measure of cell
      movement, cyclic pseudopod protrusion, and subsequent cell locomotion governed by
      chemotactic molecular transport dynamics. Chemotactic concentration gradient was
      found to influence significantly pseudopod protrusion frequency and locomotion
      speed, but not the protrusion extension. To further characterize active tumor
      cell extravasation, a process that involves dynamic tumor cell adhesion to
      vascular endothelium under flow conditions and subsequent transendothelial
      migration in response to chemotactic signals from the interstitial space, we
      developed a flow-migration chemotaxis system. This assay enabled characterization
      of tumor cell transcellular migration in terms of chemotactic signal gradients,
      shear forces, and cell-substrate adhesion. Results suggest that shear flow plays
      significant roles in tumor cell extravasation that is regulated by both tumor
      cell motility and tumor cell adhesion to endothelial molecules in a cooperative
      process.

PMID- 12051620
TI  - Signaling in the motility responses of the human neutrophil.
AB  - The neutrophil has developed into one of the most efficient vertebrate motile
      cells. It migrates through tissues, where it encounters multiple chemoattractant
      signals with complex spatial and temporal characteristics. The directional
      movement of the neutrophil is signaled by the binding of chemoattractants and
      chemokines to G-protein-coupled receptors expressed on the plasma membrane. The
      signals from the ligand-bound receptors are transmitted along signaling pathways
      and initiate various cell responses, such as motility, superoxide production, and
      secretion. The signaling of the motility responses finds its climax in the
      polymerization of F-actin, which results in lamella formation and overall
      rearrangement of the cellular cytoskeleton and cell crawling. Also, during
      motility, adhesion receptors attach to and detach from their ligands and provide
      the necessary traction for crawling. These events are highly synchronized and
      allow the cell to orient in shallow chemoattractant gradients even when more than
      one chemoattractants are present. Due to the complexity of the motility
      responses, the signaling of their regulation is still not well understood. Recent
      advances in the understanding of the mechanism of F-actin polymerization have
      shown that the small GTPasess Cdc42, Rac2, and RhoA, play a critical role in
      motility. The bound integrin receptors may also contribute to the signaling of
      motility via tyrosine kinase phosphorylation of guanine nucleotide exchange
      factors and other regulatory proteins. In this review, we discuss the signaling
      of neutrophil motility in relation to the response of the cell to chemoattractant
      activation.

PMID- 12051622
TI  - Changes of zero-bending-moment states and structures of rat arteries in response
      to a step lowering of the blood pressure.
AB  - There are many papers on tissue remodeling of blood vessels in hypertension, but
      there are few documents describing the tissue remodeling of the blood vessels
      following a step lowering of the blood pressure. The present article presents
      data on the opening angle, the vessel wall thickness, and the thicknesses of the
      intima-media and adventitia layers of the blood vessels of the lower body (the
      abdominal aorta, and the common iliac, femoral, saphenous branch, medial plantar,
      and plantar metatarsal arteries) of the rat after a step lowering of the blood
      pressure and flow by a controlled constriction of the aorta below both renal
      arteries. We found a pattern of changes that depend on space (location on the
      vascular tree), time (after the blood pressure change), and the intensity of
      disturbance. We model mathematically the dynamics shown by the experimental
      results by means of the indicial response functions, which are defined as the
      morphometric changes in response to a step decrease of blood pressure or blood
      flow. Under the hypothesis that there is a range of linearity between the degree
      of tissue remodeling and the amplitude of the pressure change, we can use the
      indicial functions to predict the remodeling of the vessel under an arbitrary
      history of decreasing blood pressure; and conversely, we can compute the indicial
      response functions from pertinent results of a single experiment. The totality of
      all our experiments is consistent with the linearity hypothesis within the range
      of the experiment. The mathematical analysis and the formulas are presented in
      the Appendix.

PMID- 12051623
TI  - A boussinesq model of natural convection in the human eye and the formation of
      Krukenberg's spindle.
AB  - The cornea of the human eye is cooled by the surrounding air and by evaporation
      of the tear film. The temperature difference between the cornea and the iris (at
      core body temperature) causes circulation of the aqueous humor in the anterior
      chamber of the eye. Others have suggested that the circulation pattern governs
      the shape of the Krukenberg spindle, a distinctive vertical band of pigment on
      the posterior cornea surface in some pathologies. We modeled aqueous humor flow
      the human eye, treating the humor as a Boussinesq fluid and setting the corneal
      temperature based on infrared surface temperature measurements. The model
      predicts convection currents in the anterior chamber with velocities comparable
      to those resulting from forced flow through the gap between the iris and lens.
      When paths of pigment particles are calculated based on the predicted flow field,
      the particles circulate throughout the anterior chamber but tend to be near the
      vertical centerline of the eye for a greatest period of time. Further, the
      particles are usually in close proximity to the cornea only when they are near
      the vertical centerline. We conclude that the convective flow pattern of aqueous
      humor is consistent with a vertical pigment spindle.

PMID- 12051621
TI  - Intracellular calcium changes in rat aortic smooth muscle cells in response to
      fluid flow.
AB  - Vascular smooth muscle cells (VSM) are normally exposed to transmural fluid flow
      shear stresses, and after vascular injury, blood flow shear stresses are imposed
      upon them. Since Ca2+ is a ubiquitous intracellular signaling molecule, we
      examined the effects of fluid flow on intracellular Ca2+ concentration in rat
      aortic smooth muscle cells to assess VSM responsiveness to shear stress. Cells
      loaded with fura 2 were exposed to steady flow shear stress levels of 0.5-10.0
      dyn/cm2 in a parallel-plate flow chamber. The percentage of cells displaying a
      rise in cytosolic Ca2+ ion concentration ([Ca2+]i) increased in response to
      increasing flow, but there was no effect of flow on the ([Ca2+]i) amplitude of
      responding cells. Addition of Gd3+ (10 microM) or thapsigargin (50 nM)
      significantly reduced the percentage of cells responding and the response
      amplitude, suggesting that influx of Ca2+ through ion channels and release from
      intracellular stores contribute to the rise in ([Ca2+]i) in response to flow. The
      addition of nifedipine (1 or 10 microM) or ryanodine (10 microM) also
      significantly reduced the response amplitude, further defining the role of ion
      channels and intracellular stores in the Ca2+ response.

PMID- 12051624
TI  - In vivo quantification of blood flow and wall shear stress in the human abdominal
      aorta during lower limb exercise.
AB  - Magnetic resonance (MR) imaging techniques and a custom MR-compatible exercise
      bicycle were used to measure, in vivo, the effects of exercise on hemodynamic
      conditions in the abdominal aorta of eleven young, healthy subjects. Heart rate
      increased from 73 +/- 6.2 beats/min at rest to 110 +/- 8.8 beats/min during
      exercise (p<0.0001). The total blood flow through the abdominal aorta increased
      from 2.9 +/- 0.6 L/min at rest to 7.2 +/- 1.4 L/min during exercise (p <0.0005)
      while blood flow to the digestive and renal circulations decreased from 2.1 +/-
      0.5 L/min at rest to 1.6 +/- 0.7 L/min during exercise (p<0.01). Infrarenal blood
      flow increased from 0.9 +/- 0.4 L/min at rest to 5.6 +/- 1.1 L/min during
      exercise (p<0.0005). Wall shear stress increased in the supraceliac aorta from
      3.5 +/- 0.8 dyn/cm2 at rest to 6.2 +/- 0.5 dyn/cm2 during exercise (p<0.0005) and
      increased in the infrarenal aorta from 1.3 +/- 0.8 dyn/cm2 at rest to 5.2 +/- 1.3
      dyn/cm2 during exercise (p<0.0005).

PMID- 12051625
TI  - Single-cell measurements of polyamidoamine dendrimer binding.
AB  - The binding of fluorescein-labeled polyamidoamine dendritic polymers (dendrimers)
      to the surface of individual fibroblast cells has been quantitatively measured
      using confocal fluorescence microscopy. Because the binding of these polymers is
      not strong, significant fluorescence from polymers in solution complicates the
      measurement, even using confocal optics. To overcome this difficulty, we have
      developed a new method employing a cell-entrapped marker dye to determine the
      extracellular volume in each voxel. This allows for a correct subtraction of
      fluorescence due to polymers in solution. We have found that, as expected, the
      larger dendrimers bound more tightly than the smaller generations, which may
      partially account for their increased efficacy in DNA transfection applications.
      The binding varied significantly from cell to cell, and an analysis of the cell
      surface area showed that this variability was not caused simply by variations in
      cell size.

PMID- 12051626
TI  - Immunohistochemical study of thyroid transcription factor-1 and HER2/neu in non
      small cell lung cancer: strong thyroid transcription factor-1 expression predicts
      better survival.
AB  - The relationship of thyroid transcription factor-1 (TTF-1) and HER2/neu
      expression in non-small cell lung cancer (NSCLC) with multiple parameters
      including survival were examined. Patients with primary NSCLC who had surgical
      resection and follow-up of at least 5 years were included in the study. There
      were 57 patients (38 men and 19 women), 44 to 75 years old (median age, 61
      years); 28 patients had adenocarcinoma (AD) and 29 had squamous cell carcinoma.
      Tumors were examined for TTF-1 and HER2/neu expression using formalin-fixed,
      paraffin-embedded tissue. Clinical and follow-up data were obtained from the
      hospital records and Cancer Center database. Representative tumor sections were
      stained using standard immunohistochemical technique and commercial antibodies
      for TTF-1 (clone 8G7G3/1, Dako) and HER2/neu (polyclonal, Dako). Tumors were
      graded as negative (<5%), weak positive (5-49%), and strong positive (>50%),
      based on the percentage of positively stained tumor cells. Statistical analyses
      were performed using log-rank test, Pearson and Spearman correlations, and Kaplan
      Meier survival curves. TTF-1 expression was seen in 45.6% of all tumors (80% of
      ADs and 14% of squamous cell carcinomas). Eighteen patients with tumors showing
      strong TTF-1 expression had significantly better survival compared with the 39
      patients whose tumors showed negative or weak TTF-1 expression, although many
      more of the higher stage AD had strong TTF-1 staining than stage I AD. The TTF-1
      expression did not correlate with tumor differentiation and was considered an
      independent predictor of survival. Seventeen of the 18 tumors with strong TTF-1
      expression were ADs. Only eight of 57 (17%) tumors showed HER2/neu expression;
      seven of these eight were ADs. Although HER2/neu expression and survival did not
      show correlation, the majority of those ADs with weak or strong HER2/neu staining
      also had strong TTF-1 staining, were mostly stage I tumors. and had overall
      longer survival. All patients with stage I disease showed better 5-year survival
      compared with those with stages II and III. Hispanic patients had significantly
      worse survival compared with Caucasians and African Americans. The results of
      this study suggest that strong expression of TTF-1 is an independent predictor of
      better survival and may be a useful prognostic tool for evaluation of patients
      with NSCLC.

PMID- 12051627
TI  - Patterns of immunoglobulin staining in paraffin-embedded malignant lymphomas.
AB  - The demonstration of immunoglobulin light chain restriction in paraffin-embedded
      B cell lymphomas is a capricious and difficult procedure that has been abandoned
      by many diagnostic laboratories. Using a combination of microwave antigen
      retrieval performed in a pressure cooker and proteolytic digestion with trypsin,
      we were able to demonstrate immunoglobulin light chain restriction in 66 B cell
      lymphomas comprising 25 follicular lymphomas, 29 diffuse large cell lymphomas, 6
      small lymphocytic lymphomas, 2 mantle cell lymphomas, 1 nodal marginal zone
      lymphoma, 1 Burkitt lymphoma, 1 hairy cell leukemia, and 1 plasmacytoma. There
      was concordance of results in 13 cases in which flow cytometry immunoglobulin
      analyzes were performed. Perinuclear staining was demonstrated in all cases with
      dot-like staining of the Golgi present in 23 cases. Perinuclear staining occurred
      in combination with cytoplasmic staining in 12 cases and membrane staining in 8
      cases with 12 lymphomas showing more than two patterns of staining.

PMID- 12051628
TI  - High frequency of MALT lymphoma in a series of 14 cases of primary breast
      lymphoma.
AB  - This article reports the clinicopathologic and immunohistochemical findings of 14
      cases fulfilling the criteria of Wiseman and Liao for primary lymphoma of the
      breast (PBL), with emphasis on the frequency of mucosa-associated lymphoid tissue
      (MALT) lymphomas. The tumors were reclassified according to the revised European
      American classification of lymphoid neoplasms. Immunohistochemistry was used to
      assist in the classification and subtyping of PBL, to demonstrate
      lymphoepithelial lesions (LEL), and to assess estrogen/progesterone receptor
      expression. Nine tumors were classified as MALT lymphomas (seven low grade and
      two high grade), four as diffuse large cell lymphomas and one as follicle center
      lymphoma. Extensive lymphoid cell infiltration of mammary ducts and acini was
      also found in non-MALT lymphoma cases. None of the 14 cases expressed hormonal
      receptors. Primary lymphoma of the breast is a rare and morphologically
      heterogeneous entity. There is similarity on the clinicopathologic overall
      profile of the current series of patients and those previously reported, but we
      recorded a higher incidence of MALT lymphoma (64.3%). Immunohistochemistry is
      mandatory to identify "true" LEL because epithelial permeation by lymphoid cells
      can also be found in non MALT-type lymphomas.

PMID- 12051629
TI  - Comparative evaluation of angiogenesis in gastric adenocarcinoma by nestin and
      CD34.
AB  - Tumor angiogenesis has been shown to be important for growth and metastasis in
      human neoplasms. Angiogenesis is usually determined by immunohistochemical
      staining of tumor tissue using various antibodies specific for endothelial cells.
      CD34 has been the one most commonly used in studies of tumor angiogenesis.
      Nestin, a class VI intermediate filament protein, was reported to be a good
      angiogenic marker in animal models. The aim of the current study was to compare
      the predictive value of angiogenesis as determined by CD34 and nestin on the same
      group of patients with advanced gastric carcinomas and to evaluate the
      possibility of nestin being a newer, better angiogenesis marker.
      Immunohistochemical staining using antinestin polyclonal antibody and anti-CD34
      monoclonal antibody was carried out on surgical specimens from 61 patients with
      advanced gastric adenocarcinomas. The sensitivity of each of the two antibodies
      was evaluated by microvessel density (MVD) measurement by counting vessels in
      three 200x fields of intense neovascularization ("hot spots") of invasive tumors
      using a digital image analyzer. Immunoreactivity for nestin and CD34 was seen in
      the endothelial cells, and no stain was noted in the negative controls. MVD
      determined by nestin [87.74 +/- 29.30 (mean +/- standard deviation)] staining was
      significantly greater than that obtained by CD34 (82.48 +/- 32.27), and the
      difference was statistically significant. There was no correlation between MVD
      and patient clinical outcome with either antibody. Interestingly, in patients
      with larger carcinomas, MVD determined by nestin correlated better with longer
      survival than CD34. The difference was statistically significant. These results
      indicate that nestin is the better marker to evaluate neovascularity in
      endothelial cells. Evaluation of MVD determined by immunohistochemistry has
      limited value in patients with gastric carcinomas.

PMID- 12051630
TI  - Use of MIB-1 in the assessment of esophageal biopsy specimens from patients with
      gastroesophageal reflux disease in well- and poorly oriented areas.
AB  - MIB-1, a proliferation marker may be useful in the assessment of esophageal
      biopsy specimens for gastroesophageal reflux disease (GERD). Forty-five
      hematoxylin and eosin-stained esophageal biopsy specimens were histologically
      assessed for basal zone height, papillary length, and inflammatory cell
      infiltrate and classified as 10 normal and 35 esophagitis. The percentage of MIB
      1-positive area (MIB-1% area) was measured on immunostained sections using image
      analysis (CAS 200) in the basal half of well-oriented areas and adjacent to five
      cross-sectioned papillae (c-pap) in poorly oriented areas. The cell layer of the
      MIB-1-positive cell furthest from the basal layer of the c-pap was also noted.
      MIB-1% area was significantly greater in both well- and poorly oriented areas of
      esophagitis biopsy specimens compared with normal biopsy specimens. MIB-1
      positivity in the basal half and c-pap were correlated (r = 0.43, p = 0.017). MIB
      1 expression correlated with basal zone height and eosinophil infiltrate (r =
      0.61, p < 0.001; r = 0.32, p = 0.03, respectively). The cell layer with positive
      cells furthest from c-pap in normal and esophagitis biopsy specimens was two and
      six layers, respectively. Using 31% as a threshold to detect abnormal findings,
      the MIB-1 sensitivity/specificity and positive predictive value in the basal half
      and c-pap were 86, 70, 91% and 80, 80, 94%, respectively. In summary, MIB-1
      staining correlates with basal zone hyperplasia and eosinophil infiltrate seen in
      GERD. MIB-1 staining can be assessed both in well- and poorly oriented areas as
      MIB-1% areas. Alternatively simply finding MIB-1 positive cells more than three
      cell layers from the basal layer is abnormal and consistent with GERD.

PMID- 12051631
TI  - Immunohistochemical localization of the IAP protein survivin in bladder mucosa
      and transitional cell carcinoma.
AB  - In the current study, the immunohistochemical localization of survivin was
      correlated with the histologic diagnosis in healthy transitional cell epithelium,
      transitional cell carcinoma (TCC) in situ, and TCC of the urinary bladder. Forty
      five TCCs (grades 1-3, 15 of each), 14 cases of TCC in situ, and II healthy
      bladder mucosal specimens were selected from archival collections of formalin
      fixed bladder tissues. Slides were reacted with an anti-survivin antibody using a
      conventional immunohistochemical method and then were scored for nuclear and
      cytoplasmic staining. Statistical analysis of survivin expression was performed
      to evaluate the correlation of staining pattern with histologic diagnosis and
      clinical outcome. Nuclear staining for survivin was detected in 26 of 45 TCCs and
      in 2 of 14 cases of TCC in situ, but was not detected in healthy bladder mucosa.
      The association of nuclear staining with TCC versus both healthy bladder mucosa
      and TCC in situ was statistically significant (P < 0.001). Patients with TCC and
      a nuclear pattern of survivin localization had a greater period of disease-free
      survival (27.2 months) than was observed in patients with TCC that showed no
      nuclear staining for survivin (9.9 months); however, the differences were not
      statistically significant. Nuclear localization of survivin is a marker of TCC
      but is rarely present in premalignant or benign bladder mucosal specimens.

PMID- 12051632
TI  - Differential expression of the PTEN tumor suppressor protein in fetal and adult
      neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly
      differentiated neuroendocrine neoplasms.
AB  - Genetic alteration and loss of expression of tumor suppressor gene PTEN has been
      found in carcinomas of the breast, prostate, and endometrium, as well as in
      gliomas. PTEN expression in neural crest/neuroendocrine (NC/NE) tissues and in
      neoplasms has not been reported. This study examines PTEN expression in
      embryonal, fetal, and adult tissues by immunohistochemistry. The authors found
      high PTEN expression in embryonal, fetal, and adult NC/NE tissues. The authors
      also study the PTEN expression in NC/NE neoplasms (N = 37), including 5
      melanocytic nevi, 2 melanomas, 9 carcinoids, 2 moderately differentiated
      neuroendocrine carcinomas, 13 poorly differentiated neuroendocrine carcinomas, 2
      paragangliomas, 2 pheochromocytomas, 2 medullary thyroid carcinomas, and 1
      neuroblastoma. All carcinoid tumors and melanocytic nevi showed moderate or
      strong immunostaining for PTEN. In contrast, the majority of poorly
      differentiated neuroendocrine carcinomas (7 of 13) were negative for PTEN (54%);
      the remainder showed diminished reactivity. The two melanomas studied were also
      negative for PTEN immunostaining. The paragangliomas, pheochromocytomas,
      medullary thyroid carcinomas, and neuroblastoma all showed a strong PTEN stain.
      The authors postulate that PTEN is a differentiation marker for NC/NE tissue and
      tumors and that loss of PTEN expression may represent an important step in the
      progression of NE tumors.

PMID- 12051633
TI  - Cytokeratin 5/6 immunostaining in hepatobiliary and pancreatic neoplasms.
AB  - Immunohistochemistry with different cytokeratin subsets has been successfully
      used in the differential diagnosis of various human epithelial neoplasms.
      Cytokeratin 5/6 antibody, which recently became commercially available, has been
      found useful in the diagnosis of mesothelioma. Studies have reported only
      infrequent staining in adenocarcinomas. We investigated the pattern of
      immunoreactivity for cytokeratin 5/6 in hepatobiliary and pancreatic tumors to
      determine its diagnostic utility in the morphologic evaluation of these
      neoplasms. Formalin-fixed. paraffin-embedded tissue sections from 10
      hepatocellular carcinomas, seven hepatocellular adenomas, 10 cholangiocarcinomas,
      10 pancreatic ductal adenocarcinomas, and 13 pancreatic neuroendocrine carcinomas
      were immunostained with anticytokeratin 5/6 after heat-induced antigen retrieval
      utilizing a modified avidin-biotin complex technique. Positive and negative
      controls stained appropriately. Two pathologists evaluated the slides. Strong but
      focal cytoplasmic immunoreactivity was observed in five of 10 pancreatic ductal
      adenocarcinomas and two of 10 cholangiocarcinomas. No immunoreactivity was
      identified in any cases of hepatocellular carcinoma (0/10), hepatocellular
      adenoma (0/7), or pancreatic neuroendocrine carcinoma (0/13). Additionally,
      occasional cytokeratin 5/6 immunoreactive benign ductal epithelial cells were
      seen in the background in some cases. Fifty percent of pancreatic ductal
      adenocarcinomas and 20% of cholangiocarcinomas are positive with anti-cytokeratin
      5/6 immunostaining. For the evaluation of poorly differentiated neoplasms in the
      liver, immunoreactivity with cytokeratin 5/6 may help to exclude the possibility
      of hepatocellular carcinoma. Cytokeratin 5/6 may be helpful as a component in the
      panel of immunostains to differentiate between poorly differentiated neoplasms.

PMID- 12051634
TI  - The spectrum of immunohistochemical reactivity of monoclonal antibody DS6 in
      nongynecologic neoplasms.
AB  - DS6 is a murine monoclonal antibody that was developed using ovarian serous
      adenocarcinoma as immunogen. DS6 reacts immunohistochemically with a tumor
      associated antigen, CA6, which has only a limited range of expression in normal
      human tissues. CA6 is most characteristically expressed in type II pneumocytes,
      fallopian tube epithelium, and urothelium, but lacks expression in mesothelium.
      The authors recently reported the spectrum of reactivity of DS6 with a wide
      variety of neoplasms of the gynecologic tract and found DS6 to be highly
      characteristic of serous neoplasms. CA6 is also expressed in other mullerian
      derived epithelial neoplasms of the gynecologic tissues, but is not typically
      expressed by ovarian intestinal-type mucinous neoplasms, mesothelioma,
      mesenchymal neoplasms, ovarian germ cell tumors, or sex cord-stromal neoplasms.
      In this study, the authors tested the monoclonal antibody DS6 with 1,202
      nongynecologic neoplasms to characterize the full range of expression of antigen
      CA6. This study has shown that CA6 is highly expressed by many carcinomas of
      breast, pancreas, and urothelium, and also shows expression in some carcinomas of
      renal and pulmonary origin, and some neoplasms of other sites. DS6
      immunoreactivity is not seen in the majority of neoplasms with hematopoietic,
      mesenchymal, or germ cell differentiation.

PMID- 12051635
TI  - Calretinin: a valuable marker of normal and neoplastic Leydig cells of the
      testis.
AB  - Sex cord-stromal tumors represent approximately 4% of all testicular neoplasms.
      Leydig cell tumor (LCT) is the most common entity, followed by Sertoli cell tumor
      (SCT). Leydig cell tumor histologic diagnosis is usually easy, but occasional
      forms of LCT could mimic others neoplasms, especially SCT or variants of yolk sac
      tumor. The aim of this study was to investigate calretinin expression in LCT and
      SCT of the testis. We evaluated calretinin reactivity in formalin-fixed, paraffin
      embedded sections of 10 LCT, three SCT, five Leydig cell hyperplasia, two Sertoli
      cell adenomas, eight seminomatous tumors, five nonseminomatous germ cell tumors
      (mixed tumor), one adenomatoid tumor, and two normal testes using a standard
      immunohistochemical technique with a microwave-mediated epitope retrieval. All
      cases of LCT showed a positive staining that was diffuse and intense, constantly
      cytoplasmic, and sometimes nuclear. A positive strong and diffuse cytoplasmic and
      sometimes nuclear staining was also observed in Leydig cell hyperplasia and in
      normal Leydig cells. No staining was seen in two of three cases of SCT, and focal
      staining was observed in the third case. Only rare scattered cells were weakly
      immunostained in the Sertoli cell nodules. Seminomatous and nonseminomatous germ
      cell tumors were negative. Calretinin is an interesting marker of normal and
      neoplastic Leydig cells of the testis and may be of value in the diagnosis of
      atypical LCT.

PMID- 12051636
TI  - Comparison of primary and secondary cutaneous CD56+ NK/T cell lymphomas.
AB  - CD56+ NK/T cell lymphoma (NKTL) frequently involves skin and subcutaneous tissue.
      The characteristics of primary cutaneous nasal-type CD56+ NKTLs and secondary
      cutaneous involvement of nasal CD56+ NKTLs have not been clearly separated. This
      retrospective study analyzed 15 cases of NKTL (10 primary CD56+ NKTLs and 5
      secondary CD56+ NKTLs) for their clinicopathologic and immunophenotypic
      characteristics using CD3, CD4, CD20, CD45RO, CD56, TIA-1, CD30, and Ki-67
      antigens. In situ hybridization for Epstein-Barr virus RNA (EBERISH) and PCR for
      T cell receptor (TCR) gamma gene rearrangement were also performed. Clinically,
      NKTL-P was seen with equal frequency among male (five cases) and female (five
      cases) patients and presented with subcutaneous nodules without epidermal changes
      (nine cases), whereas all cases of NKTL-S occurred in male patients and presented
      with nodules or plaques with distinct epidermal changes (five cases).
      Microscopically, initial NKTL-P lesions had the panniculitic patterns of small to
      medium-sized cells (nine cases). NKTL-S lesions were extensive in both subcutis
      and dermis, with larger and more pleomorphic tumor cells (four cases) that also
      showed signs epidermotropism (five cases). In initial biopsies of CD56+ NKTL-P, a
      minority of tumor cells showed signals for EBERISH and in biopsies of CD56+ NKTL
      S, virtually every tumor cell showed signals. While all five patients with
      secondary CD56+ NKTL died of disease with widespread systemic involvement within
      16 months after onset of skin lesions, 7 out of the 10 primary CD56+ NKTL
      patients survived more than 20 months after onset of skin lesions, with slow
      progression and episodic recurrences. The primary and secondary cutaneous CD56+
      NKTLs showed considerable clinicopathologic differences, suggesting differences
      in pathogenesis.

PMID- 12051638
TI  - Diagnostic use of muscle markers in the cytologic evaluation of serous fluids.
AB  - Differentiating reactive mesothelial cells from malignant mesotheliomas and from
      adenocarcinomas can be diagnostically challenging when based solely on the
      morphologic examination of serous fluids. The diagnosis even after the use of
      standard immunohistochemical stains may at times be inconclusive because of the
      variable reactivity of mesothelial cells for these markers. Pathologists and
      cytologists underutilize reactivity for desmin, a feature of mesothelial cells
      apparently not shared by adenocarcinomas. The purpose of this study was to
      evaluate the extent to which mesothelial cells express muscle differentiation and
      to assess the diagnostic utility of muscle markers in distinguishing reactive
      mesothelial cells from malignant mesotheliomas and adenocarcinomas. Archival
      paraffin-embedded cell blocks of serous fluids from 24 cases of reactive
      mesothelial cells, 14 cases of malignant mesothelioma, and 56 cases (14 cases
      from each) of metastatic adenocarcinoma from the lung, breast, ovary, and
      gastrointestinal tract were retrieved. Five cases of omentum with unremarkable
      mesothelial cells were also included in the study. All cases were stained for
      desmin, actin, myoglobin, and myogenin and evaluated independently by two
      observers. Strong cytoplasmic reactivity for desmin was noted in 22 of 24 cases
      (92%) of reactive mesothelial cells. The reactive mesothelial cells did not
      express actin, myoglobin, or myogenin. All cases of malignant mesothelioma and
      metastatic adenocarcinoma were negative for the four muscle markers. The
      mesothelial lining and scattered subserosal cells in the omental sections were
      positive for desmin. Because desmin was expressed only in benign mesothelial
      cells, it may serve as a reliable marker in distinguishing reactive mesothelial
      cells from mesothelioma or from adenocarcinoma. Awareness of this staining
      pattern is also important to avoid pitfalls when evaluating body fluid specimens
      from patients with a history of tumors expressing muscle differentiation.

PMID- 12051637
TI  - Evaluation of Th-1 and Th-2 immune responses in the skin lesions of patients with
      Blau syndrome.
AB  - Blau syndrome is an autosomal dominant syndrome characterized by arthritis,
      uveitis, skin rash, granuloma, and camptodactyly. It has overlapping symptoms
      with sarcoidosis and rheumatoid arthritis. Our study was directed toward
      determining the role of cytokines in granuloma formation in Blau syndrome.
      Antigenic stimulation usually follows two pathways: Th-1, which activates
      macrophages and cytotoxic T-lymphocytes and produces interleukin (IL)-2, IL-3,
      interferon gamma, and tumor necrosis factor alpha, and Th-2, which activates the
      humoral immune system and produces IL-4, IL-5, and IL-10. The development of
      cytokine profiles may shed some light on our understanding of this illness.
      Therefore, we studied the relative roles of two opposing lymphocytes, Th-1 and Th
      2, by analyzing their relative expression in the skin lesions of patients with
      Blau syndrome, using the in situ reverse transcription-polymerase chain reaction
      technique. Our data revealed a significant upregulation of IL-2, an event that
      appears to play an important role in the formation of granuloma and in the
      pathogenesis of Blau syndrome. Expression of IL-10, however, was downregulated,
      and this may have an inhibitory role in the development of the disease. Further
      studies would be necessary to confirm the presence of other cytokines and to
      establish the regulatory roles of Th-1 and Th-2 lymphocytes in the pathogenesis
      of Blau syndrome.

PMID- 12051639
TI  - Effect of prolonged formalin fixation on the immunohistochemical reactivity of
      breast markers.
AB  - Prolonged formalin fixation is known to reduce the immunohistochemical reactivity
      of many paraffin section antibodies. Before the common use of heat induced
      epitope retrieval methods, vimentin reactivity was proposed as a marker of
      antigen preservation. To evaluate the effect of formalin fixation on breast tumor
      markers, multitumor blocks of tissue fixed in formalin for varying time intervals
      from 33 different infiltrating breast carcinomas were analyzed for the expression
      of estrogen receptor (ER), progesterone receptor (PR), c-erb-B2, Ki-67, p27, and
      vimentin. The mean/median length of the longest fixation time per specimen was
      53/42 days (range 7 days-154 days). Formalin fixation did not significantly
      reduce immunoreactivity for Ki-67, p27, or vimentin, even in tissue fixed for 154
      days. Of 23 ER-positive cases, a significant reduction in immunoreactivity (2
      grades or more) was identified in three samples, occurring at 57 to 64 days. For
      21 PR-positive cases, only one showed a significant reduction (from 3+ to 1+) at
      120 days. Of nine c-erb-B2 positive (2 + or 3+) cases, four became negative (1+
      or 0) at 20, 42, 49, and 99 days. The immunoreactivity of some breast prognostic
      markers is reduced by formalin over-fixation, but only after extensive fixation
      that may not be clinically relevant. The loss of antigen preservation is not
      accompanied by a loss of vimentin immunoreactivity, making vimentin a suboptimal
      marker for ER, PR, or c-erb-B2 preservation.

PMID- 12051640
TI  - Detection of numerical chromosomal abnormalities in epithelial ovarian neoplasms
      by fluorescence in situ hybridization (FISH) and a review of the current
      literature.
AB  - Preliminary retrospective chromosomal analysis was performed using fluorescence
      in situ hybridization (FISH) with alphoid DNA probes for chromosomes 1, 3, 6, 8,
      12, 17, and X. Twenty-four epithelial ovarian tumors were examined in this pilot
      study, including 8 borderline (LMP) serous tumors, 9 serous carcinoma, and 7
      mucinous carcinoma. Hybridization signals were counted to demonstrate the
      frequency of aneusomy, trace chromosomal progression, and identify the
      predominance of chromosome copy number abnormalities that are specific to a
      particular histotype. The preliminary results revealed almost an equal number of
      mean aneusomies in serous (58.13 +/- 13%) and mucinous (64.33 +/- 10%) carcinoma,
      both of which were slightly higher than borderline serous tumors (50.57 +/- 17%).
      Hyposomies 3 and X were significantly higher in mucinous than in serous ovarian
      carcinomas, and lowest in borderline serous tumors (P<0.05 and P<0.01). Signal
      losses were a more frequent abnormality in all three histologic subtypes.
      Mucinous carcinomas showed a loss of chromosomes 8 (45.00 +/- 28%) and 3 (43.14
      +/- 16%), in addition to a loss of chromosome X (56.29 +/- 12%). Serous
      carcinomas showed a gain of chromosome 1 (39.44 +/- 32%), followed by losses of
      chromosomes 6 (37.00 +/- 20%), 17 (36.44 +/- 19%), and 8 (36.89 +/- 19%). In
      borderline serous tumors, the most frequent findings were losses of chromosomes 6
      (38.00 +/- 17%), 12 (36.88 +/- 17%), and 3 (36.13 +/- 21%). However, further
      research is necessary to substantiate these preliminary results and elucidate
      their clinical significance. A brief review of the literature pertaining to
      interphase cytogenetics in ovarian epithelial tumors is discussed also.

PMID- 12051641
TI  - Cytokeratin-positive interstitial reticulum cells in Kikuchi-Fujimoto disease.

PMID- 12051642
TI  - Re: Skacel M, Skilton B, Pettay JD, Tubbs RR. Tissue microarrays: a powerful tool
      for high-throughput analysis of clinical specimens. Appl Immunohistochem Molecul
      Morphol 2002;10:1-6.

PMID- 12051643
TI  - Thyroid transcription factor-1: a review.
AB  - Thyroid transcription factor-1 (TTF-1) is a 38-kd homeodomain containing DNA
      binding protein originally identified in follicular cells of the thyroid and
      subsequently in pneumocytes. This review focuses on the utility of antisera in
      TTF-1 immunohistochemical staining in the diagnosis of neoplastic conditions.
      Based on published studies to date, anti-TTF-1 is a very useful reagent in
      distinguishing pulmonary adenocarcinoma from other primary carcinomas,
      identifying differentiated thyroid neoplasms, distinguishing mesothelioma from
      pulmonary adenocarcinoma, and distinguishing small cell carcinoma of the lung
      from Merkel cell carcinoma. It may also be useful in distinguishing
      neuroendocrine (NE) tumors of the lung from well-differentiated NE tumors from
      other sites, such as the intestine.

PMID- 12051644
TI  - Detection of intermediate metabolites of benzene biodegradation under
      microaerophilic conditions.
AB  - The intermediate metabolites of benzene transformation by a microaerophilic
      bacterial consortium, adapted to degrade gasoline and benzene at low
      concentrations of dissolved oxygen (<1 mg l(-1)), were identified. The examined
      range of initial DO concentration, 0.05 to 1 mg l(-1), was considerably lower
      than the previously reported values believed to be necessary to initiate benzene
      biodegradation. An extensive transformation of benzene. higher than the
      theoretical predictions for its aerobic oxidation, was observed. Phenol was
      identified as the most stable and the major intermediate metabolite which was
      subsequently transformed into catechol and benzoate. The use of 13C-labeled
      compounds identified benzene as the source of phenol, and phenol as the source of
      catechol and benzoate, suggesting the involvement of a monooxygenase enzymatic
      system in biodegradation of benzene at low DO concentrations. A metabolic
      sequence was proposed to describe the simultaneous detection of catechol and
      benzoate during the microaerophilic transformation of benzene. The results of
      this work demonstrate that it is possible to transform benzene, a highly
      carcinogenic hydrocarbon and a major contaminant of groundwater, to more easily
      biodegradable compounds in the presence of very small amounts of oxygen.

PMID- 12051645
TI  - Fluoranthene degradation in Pseudomonas alcaligenes PA-10.
AB  - Pseudomonas alcaligenes strain PA-10 degrades the four-ring polycyclic aromatic
      hydrocarbon fluoranthene, co-metabolically. HPLC analysis of the growth medium
      identified four intermediates, 9-fluorenone-1-carboxylic acid; 9-hydroxy-1
      fluorene carboxylic acid; 9-fluorenone and 9-fluorenol, formed during
      fluoranthene degradation. Pre-exposure of PA-10 to 9-fluorenone-1-carboxylic acid
      and 9-hydroxy-1-fluorene-carboxylic acid resulted in increases in fluoranthene
      removal, while pre-exposure to 9-fluorenone and 9-fluorenol resulted in a
      decrease in fluoranthene degradation. The rate of indole transformation was
      similarly affected by pre-exposure to these metabolic intermediates, indicating a
      link between fluoranthene degradation and indigo formation in this strain.

PMID- 12051646
TI  - Uranyl precipitation by biomass from an enhanced biological phosphorus removal
      reactor.
AB  - Heavy metal and radionuclide contamination presents a significant environmental
      problem worldwide. Precipitation of heavy metals on membranes of cells that
      secrete phosphate has been shown to be an effective method of reducing the volume
      of these wastes, thus reducing the cost of disposal. A consortium of organisms,
      some of which secrete large quantities of phosphate, was enriched in a laboratory
      scale sequencing batch reactor performing Enhanced Biological Phosphorus Removal,
      a treatment process widely used for removing phosphorus. Organisms collected
      after the aerobic phase of this process secreted phosphate and precipitated
      greater than 98% of the uranyl from a 1.5 mM uranyl nitrate solution when
      supplemented with an organic acid as a carbon source under anaerobic conditions.
      Transmission electron microscopy, energy dispersive x-ray spectroscopy, and
      fluorescence spectroscopy were used to identify the precipitate as membrane
      associated uranyl phosphate, UO2HPO4.

PMID- 12051647
TI  - Metal binding by pyridine-2,6-bis(monothiocarboxylic acid), a biochelator
      produced by Pseudomonas stutzeri and Pseudomonas putida.
AB  - Pyridine-2,6-bis(monothiocarboxylic acid) (pdtc), a natural metal chelator
      produced by Pseudomonas stutzeri and Pseudomonas putida that promotes the
      degradation of carbon tetrachloride, was synthesized and studied by
      potentiometric and spectrophotometric techniques. The first two stepwise
      protonation constants (pK) for successive proton addition to pdtc were found to
      be 5.48 and 2.58. The third stepwise protonation constant was estimated to be
      1.3. The stability (affinity) constants for iron(III), nickel(II), and
      cobalt(III) were determined by potentiometric or spectrophotometric titration.
      The results show that pdtc has strong affinity for Fe(III) and comparable
      affinities for various other metals. The stability constants (log K) are 33.93
      for Co(pdtc)2(1-); 33.36 for Fe(pdtc)2(1-); and 33.28 for Ni(pdtc)2(2-). These
      protonation constants and high affinity constants show that over a physiological
      pH range the ferric pdtc complex has one of the highest effective stability
      constants for iron binding among known bacterial chelators.

PMID- 12051648
TI  - Degradation of dissolved and sorbed 2,4-dichlorophenol in soil columns by
      suspended and sorbed bacteria.
AB  - The influence of sorption of bacteria, as well as 2,4-dichlorophenol (2,4-DCP),
      on the mineralization of 100 microg l(-1) of the organic compound was examined in
      an aquifer material under advective flow conditions (column displacement
      technique). The study was designed to distinguish the rates and extent of
      biodegradation of the sorbed and the dissolved trace organic and the contribution
      of sorbed and suspended bacteria to the degradation. The degradation of dissolved
      2,4-DCP was significantly faster than the degradation of the same compound sorbed
      to the solids, and suspended bacteria degraded the dissolved compound at a higher
      rate than sorbed bacteria, also on a per cell basis. The suspended bacteria
      degraded 8-12% of the added dissolved 2.4-DCP, while sorbed bacteria made a
      smaller contribution by degrading about 5% of sorbed 2,4-DCP. No degradation was
      seen with sorbed 2,4-DCP and suspended bacteria, and a marginal contribution was
      made by sorbed bacteria on the degradation of dissolved 2,4-DCP (<0.4%).

PMID- 12051649
TI  - Naphthalene, phenanthrene and surfactant biodegradation.
AB  - The impact of surfactants on naphthalene and phenanthrene biodegradation and vice
      versa after surfactant flushing were evaluated using two anionic surfactants:
      sodium dodecyl sulfate (SDS) and sodium dodecyl benzene sulfonate (SDBS); and two
      nonionic surfactants: POE (20) sorbitan monooleate (T-maz-80) and octylphenol
      poly(ethyleneoxy) ethanol (CA-620). Naphthalene and phenanthrene biodegradation
      varied differently in the presence of different surfactants. Naphthalene
      biodegradation was not impacted by the presence of SDS. In the presence of T-maz
      80 and CA-620, naphthalene biodegradation occurred at a lower rate (0.14 d(-1)
      for T-maz-80 and 0.19 d(-1) for CA-620) as compared to un-amended control (0.29
      d(-1)). Naphthalene biodegradation was inhibited by the presence of SDBS. In the
      presence of SDS, phenanthrene biodegradation occurred at a lower rate (0.10 d(-1)
      as compared to un-amended control of 0.17 d(-1)) and the presence of SDBS, CA-620
      and T-maz-80 inhibited phenanthrene biodegradation. The surfactants also
      responded differently to the presence of naphthalene and phenanthrene. In the
      presence of naphthalene, SDS biodegradation was inhibited; SDBS and T-maz-80
      depleted at a lower rate (0.41 d(-1) and 0.12 d(-1) as compared to 0.48 d(-1) and
      0.22 d(-1)). In the absence of naphthalene, CA-620 was not degradable, while in
      the presence of naphthalene, CA-620 began to degrade at a comparatively low rate
      (0.12 d(-1)). In the presence of phenanthrene, SDS biodegradation occurred at a
      lower rate (1.2 d(-1) as compared to 1.68 d(-1)) and a similar trend was observed
      for T-maz-80. The depletion of SDBS and CA-620 did not change significantly. The
      choice of SDS for naphthalene-contaminated sites would not adversely affect the
      natural attenuation of naphthalene, in addition, naphthalene was preferentially
      utilized to SDS by naphthalene-acclimated microorganisms. Therefore, SDS was the
      best choice. T-maz-80 was also found to be usable in naphthalene-contaminated
      sites. For phenanthrene contaminated sites, SDS was the only choice.

PMID- 12051650
TI  - Biotransformation of linear alkylbenzene sulfonate (LAS) by Phanerochaete
      chrysosporium: oxidation of alkyl side-chain.
AB  - The white rot fungus Phanerochaete chrysosporium, which generally mineralizes
      substituted aromatics to CO2, transformed linear alkylbenzene sulfonate (LAS)
      surfactants mainly at their alkyl side chain. Degradation of LAS was evidenced by
      a zone of clearing on LAS-containing agar plates and colorimetric analysis of
      liquid cultures. Disappearance of LAS was virtually complete within 10 days in
      low nitrogen (2.4 mM N), high nitrogen (24 mM N) and malt extract (ME) liquid
      media. After 5 days of incubation in ME medium, transformation of LAS was
      complete at concentrations < or = 4 mg l(-1), but decreased at higher
      concentrations. The LAS degradation was not dependent on lignin peroxidases
      (LiPs) and manganese-dependent peroxidases (MnPs). Mineralization of 14C-ring-LAS
      to 14CO2 by P. chrysosporium was < 1% regardless of the culture conditions used.
      Thin layer chromatography and mass spectral analyses indicated that P.
      chrysosporium transformed LAS to sulfophenyl carboxylates (SPCs) through
      oxidative shortening of the alkyl side-chains. While LAS disappearance in the
      cultures was not dependent on LiPs and MnPs, transformation of the parent LAS
      moieties to SPCs was more extensive in low N medium that favors expression of
      these enzymes. The SPCs produced in LN cultures were shorter in chain- length
      than those produced in ME cultures. Also there was a notable shift in the
      relative abundance of odd and even chain length metabolites compared to the
      starting LAS particularly in the low N cultures suggesting the possible
      involvement of processes other than or in addition to beta-oxidation in the chain
      shortening process.

PMID- 12051651
TI  - The roles of intermediates in biodegradation of benzene, toluene, and p-xylene by
      Pseudomonas putida F1.
AB  - Several types of biodegradation experiments with benzene, toluene, or p-xylene
      show accumulation of intermediates by Pseudomonas putida F1. Under aerobic
      conditions, the major intermediates identified for benzene, toluene, and p-xylene
      are catechol, 3-methylcatechol, and 3,6-dimethylcatechol, respectively.
      Oxidations of catechol and 3-methylcatechol are linked to biomass synthesis. When
      oxygen is limited in the system, phenol (from benzene) and m-cresol and o-cresol
      (from toluene) accumulate.

PMID- 12051652
TI  - A two-step model for the kinetics of BTX degradation and intermediate formation
      by Pseudomonas putida F1.
AB  - A two-step model is developed for the aerobic biodegradation of benzene, toluene,
      and p-xylene (BTX) by Pseudomonas putida F1. The model contains three unique
      features. First, an initial dioxygenation step transforms BTX into their catechol
      intermediates, but does not support biomass growth. Second, the benzene or
      toluene intermediates are mineralized, which supports biomass synthesis. Third,
      BTX exhibit competitive inhibition on each other's transformation, while toluene
      and benzene noncompetitively inhibit the mineralization of their catechol
      intermediate. A suite of batch and chemostat experiments is used to
      systematically measure the kinetic parameters for the two-step transformations
      and the substrate interactions.

PMID- 12051653
TI  - Discussion on the "Alternatives search" requirement.

PMID- 12051654
TI  - An ode to reviewers, and other things.

PMID- 12051655
TI  - Engineering control of airborne disease transmission in animal laboratories.
AB  - We here present a review of the problem of controlling airborne disease
      transmission in animal research facilities, with emphasis on engineering design
      and air-treatment technologies. Dilution ventilation, pressurization control,
      source control, and air disinfection and removal systems are reviewed, and
      analytical studies on the effects of dilution ventilation, filtration, and
      ultraviolet germicidal irradiation are summarized. In addition, we discuss
      practical problems common to laboratory facilities and present a database of
      potential airborne pathogens and allergens that can be transmitted between humans
      and animals. We offer some conclusions regarding the design and selection of
      available technologies and components and provide cost estimates for various air
      cleaning systems.

PMID- 12051656
TI  - Outbreak: detection and investigation.
AB  - With the increased movement of rodents between institutions of various pathogen
      status, the risk of introducing unwanted agents into a facility is high. This
      situation is in direct conflict with the increasing demand for "clean" rodents
      for use in biomedical research. If an institution is to have any hope of
      attaining specific-pathogen-free status, a rational surveillance program should
      be in place, along with a plan of action to be undertaken when an unwanted agent
      is detected in the facility. This review summarizes the factors that should be
      considered when designing a rodent health-surveillance program and outlines a
      general approach to be taken when rodents in a facility become infected with an
      undesirable agent.

PMID- 12051658
TI  - A technique for creating localized subcutaneous Blastomyces granulomas in rats.
AB  - Our purpose was to develop a simple, reliable method for creating subcutaneous
      Blastomyces dermatitidis nodules in rats and to describe the histologic
      appearance of these lesions. We used B. dermatitidis isolated from a dog with
      blastomycosis to prepare a Blastomyces yeast suspension. Four rats were used to
      test initial dose concentrations of 10(5), 10(6), 10(9), and 10(10) yeast
      organisms. The dose was administered subcutaneously over the distal tibia in a
      volume of 0.1 ml. We then inoculated 35 additional rats with 10(9) or 10(10)
      yeast organisms. Rats were euthanized 7, 10, 14, 21, or 28 days after
      inoculation, and the histologic appearance of the nodules was described. A full
      post-mortem examination sought evidence of systemic spread of Blastomyces
      organisms. We successfully induced subcutaneous Blastomyces abscesses in 34 of 37
      rats injected with 10(9) or 10(10) organisms. Nodules first appeared 3 to 7 days
      after injection and reached 2 to 15 mm in diameter by 7 to 28 days after
      inoculation. Histologically the lesions were characterized by a necrotic center
      surrounded by a layer of viable yeast and granulomatous inflammation. Live yeast
      organisms were recovered from all lesions. No adverse effects or systemic spread
      of Blastomyces organisms were observed. We conclude that subcutaneous Blastomyces
      abscesses can be induced safely and reliably in rats after injection of 10(9) and
      10(10) organisms. Histologically, the experimentally induced lesions share both
      similarities to and differences with lesions of naturally occurring
      blastomycosis.

PMID- 12051657
TI  - Fentanyl-fluanisone-midazolam combination results in more stable hemodynamics
      than does urethane alpha-chloralose and 2,2,2-tribromoethanol in mice.
AB  - Near-physiologic hemodynamic conditions for several hours were needed to study
      cardiovascular physiology in a murine model. We compared two commonly used
      anesthetic treatments, urethane alpha-chloralose (U-alphaCh; 968 mg U and 65 mg
      alphaCh/kg) and 2,2,2-tribromoethanol (TBE; 435 mg/kg) and fentanyl fluanisone
      midazolam (FFM; 3.313 mg fentanyl, 104.8 mg fluanisone, and 52.42 mg
      midazolam/kg) with respect to mean arterial blood pressure (MAP) and heart rate
      (HR) for 100 min at similar levels of surgical anesthesia. Assessed every 10 to
      15 min, the U-alphaCh+TBE group maintained a significantly (P < 0.001) lower mean
      MAP (49 4 mmHg) than did the FFM group (78 5 mmHg). Mean HR in the U-alphaCh+TBE
      group significantly (P < 0.001) increased from 308 34 bpm at the beginning to 477
      43 bpm at the end of the experiment. In comparison, the FFM group showed a stable
      HR of 431 37 bpm. The MAP and HR of the U-alphaCh+TBE group were extremely
      unstable, with sudden and unpredictable changes in MAP when examined at 1-min
      intervals. The results of our study show that U-alphaCh+TBE anesthesia should not
      be used in murine models in which stable, near-physiologic hemodynamics are
      needed for cardiovascular studies.

PMID- 12051659
TI  - Isomeric N-alkylpyridylporphyrins and their Zn(II) complexes: inactive as SOD
      mimics but powerful photosensitizers.
AB  - The ortho, meta, and para isomers of cationic N-alkylpyridylporphyrins and their
      Zn(II) complexes were compared in terms of their photodynamic properties. The
      ortho Zn(II) complex was found to be the most efficient in causing photooxidation
      of NADH in vitro. In Escherichia coli, however, the para and meta isomers were
      better photosensitizers than their ortho analogs. The lower potency of the ortho
      compound in vivo seems to be due to its lower intracellular concentration. All
      porphyrins tested were more efficient in killing E. coli and in photooxidizing
      NADH than the hematoporphyrin derivative. Antibiotic resistance did not affect
      the photokill, which implies that the cationic N-alkylpyridylporphyrins, as their
      Zn(II) complexes, can be used as bactericidal agents against antibiotic-resistant
      strains of gram-negative bacteria.

PMID- 12051661
TI  - Conditional expression of a constitutively active aryl hydrocarbon receptor in
      MCF-7 human breast cancer cells.
AB  - In addition to inducing transcription of a battery of target genes encoding drug
      metabolizing enzymes, the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) is known to induce antiestrogenic responses. However, the
      mechanisms underlying such complex biologic responses affecting growth and
      differentiation remain unclear. In the present study we have investigated
      biological effects of a constitutively active mutant of the aryl hydrocarbon (Ah)
      receptor (CA-AhR), in particular whether it modulates estrogen receptor function
      in human MCF-7 breast cancer cells. To this end, the CA-AhR protein was
      conditionally expressed using the tet repressor. Expression of CA-AhR resulted in
      constitutive formation of a DNA-binding AhR-aryl hydrocarbon receptor nuclear
      translocator heterodimeric complex and enhanced expression of the Ah receptor
      target gene CYP1A1 in the absence of TCDD. Moreover, expression of CA-AhR
      inhibited estrogen-dependent cathepsin D expression and growth of these cells.
      Thus, the present model system conditionally expressing the CA-AhR protein
      provides a novel tool for the investigation of AhR-mediated signaling pathways.

PMID- 12051660
TI  - Nitroxyl (NO-): a substrate for superoxide dismutase.
AB  - The interactions of Cu, Zn superoxide dismutase (SOD) with nitroxyl (NO-) and
      nitric oxide (NO), both of which are thought to be biologically significant, have
      been studied but remain undefined. Having previously noted that NO- can reduce Cu
      (II), Zn SOD aerobically, we now report that it also can do so anaerobically and
      that Cu, Zn SOD can catalyze the elimination of NO(-) in the absence of O2.NO-
      acts as a reductant of ferricytochrome c anaerobically, but in the presence of O2
      causes the oxidation of ferrocytochrome c and NADPH. Equivalent fluxes of NO-,
      and NO + O2- were able to comparably oxidize NADPH, but the oxidation by NO + O2-
      was more than fivefold more sensitive to inhibition by Cu, Zn SOD than was the
      oxidation by NO-. Thus Cu, Zn SOD inhibited NADPH oxidation by NO- by a route
      independent of catalyzing the dismutation of O2. Plausible mechanisms for those
      observations are offered and rate constants are estimated.

PMID- 12051662
TI  - Inhibition of cathepsin G by 2-amino-3,1-benzoxazin-4-ones: kinetic
      investigations and docking studies.
AB  - A series of benzoxazinones was used to investigate the interaction of human
      cathepsin G with acyl-enzyme inhibitors. With respect to the primary specificity
      of cathepsin G, inhibitors with hydrophobic or basic residues at position 2 were
      included in the study. Parameters of the enzyme acylation and deacylation were
      determined by slow-binding kinetics in the presence of a chromogenic substrate.
      For selected inhibitors, the time course of the enzyme-catalyzed conversion of
      the inhibitors was followed. This approach was suitable to elucidate a rate
      determining deacylation step. Docking simulations of the noncovalent enzyme
      inhibitor complexes were performed and several clusters were analyzed for each
      inhibitor. The amino acids of the active site that participate in the binding of
      the inhibitors were determined. The arrangements in several clusters of an
      inhibitor were not uniform with respect to the orientation by which the inhibitor
      was bound in the S(1) pocket. Docking of the basic piperazino derivatives 6 and
      10 indicated an interaction with Glu 226 at the bottom of the S(1) specificity
      pocket. The (N-methyl)benzylamino derivative 1 showed the strongest acylation
      rate (k(on)=1200 M(-1) s(-1)), which was attributed to a high extent of pseudo
      productive orientations of the noncovalent preassociation complex.

PMID- 12051663
TI  - Purification, characterization, and crystallization of alliinase from garlic.
AB  - Glycosylated dimeric alliinase (EC 4.4.1.4) was purified to homogeneity from its
      natural source, garlic. With 660 units/mg, the specific enzymatic activity of the
      pure enzyme is the highest reported to date. Based on both CD spectroscopy data
      and sequence-derived secondary structure prediction, the alpha-helix content of
      alliinase was estimated to be about 30%. Comparisons of all available amino acid
      sequences of alliinases revealed a common cysteine pattern of the type C-x18-19-C
      x-C-x2-C-x5-C-x6-C in the N-terminal part of the sequences. This pattern is
      conserved in alliinases but absent in other pyridoxal 5'-phosphate-dependent
      enzymes. It suggests the presence of an epidermal growth factor-like domain in
      the three-dimensional structures of alliinases, making them unique among the
      various families of pyridoxal 5'-phosphate-dependent enzymes. Well-ordered three
      dimensional crystals of garlic alliinase were obtained in four different forms.
      The best diffraction was observed with crystal form IV (space group
      P2(1)2(1)2(1), a=68.4, b=101.1, c=155.7 A) grown from an ammonium sulfate
      solution. These crystals diffract to at least 1.5 A resolution at a synchrotron
      source and are suitable for structure determination.

PMID- 12051664
TI  - Secretion polarity of interferon-beta in epithelial cell lines.
AB  - Epithelial cells are an attractive target for local gene delivery in gene therapy
      for which cytokine genes such as interferon (IFN) genes are promising. However,
      how the secretion of the gene products is regulated in epithelial cells has been
      insufficiently investigated. Here, we have studied the secretion polarity of IFN
      beta expressed via gene transfection in mouse epithelial Pam-T cells on a
      bicameral culture system. In transient expression, IFN-beta was predominantly
      secreted from the cell membrane side on which the transfection was carried out.
      Meanwhile, the secretion of constitutive IFN-beta from stable transformants was
      apparently unpolarized. Interestingly, the transformants displayed a polarized
      secretion of transiently expressed IFN-beta in a transfection-side-dependent
      manner, their stable IFN-beta secretion remaining unpolarized. These results
      suggest that epithelial cells have at least dual protein sorting-secretion
      pathways, transient and stable, for the same secretory proteins, such as IFNs.

PMID- 12051665
TI  - 7-Ketocholesterol and staurosporine induce opposite changes in intracellular pH,
      associated with distinct types of cell death in ECV304 cells.
AB  - Incubation of ECV304 cells with 7-ketocholesterol, a lipid component of oxidized
      low-density lipoproteins, caused a concentration- and time-dependent decrease in
      the number of viable cells. Other cholesterol oxides, 7 beta-hydroxycholesterol
      and 25-hydroxycholesterol, but not cholesterol, were only weakly cytotoxic. No
      evidence for activation of caspase-3 and -8, DNA laddering, or release of
      cytochrome c from mitochondria into the cytoplasm was obtained in 7
      ketocholesterol-treated cells, indicating that cell death was not due to
      apoptosis. As a positive control for apoptosis, ECV304 cells were treated with
      staurosporine, which indeed caused significant activation of caspase-3 activity,
      DNA laddering, and cytochrome c release. Cellular morphology and actin
      cytoskeletal organization were distinctly different after exposure to the two
      drugs. Furthermore, staurosporine caused intracellular acidification, whereas 7
      ketocholesterol induced a significant alkalinization, which was abolished by 4,4'
      diisothiocyanatodihydrostilbene-2,2'-disulfonic acid. In conclusion, in ECV304
      cells 7-ketocholesterol induces some typical hallmarks of necrotic cell death but
      not of apoptosis.

PMID- 12051666
TI  - Noninvasive diagnostic tool for inflammation-induced oxidative stress using
      electron spin resonance spectroscopy and an extracellular cyclic hydroxylamine.
AB  - Inflammation is one of the leading causes of the many pathological states
      associated with oxidative stress. A crucial role in the development of
      inflammation-induced oxidative stress is played by reactive oxidant species
      (ROS), which are very difficult to detect in vivo. One of the most sensitive and
      definitive methods in the detection of ROS is electron spin resonance, especially
      as used in conjunction with spin trapping. Unfortunately, the commonly used
      nitrone spin traps have a very low efficacy for trapping superoxide radicals, and
      their radical adducts are not stable. To address this deficiency, we have
      developed negatively charged cyclic hydroxylamines such as 1-hydroxy-4
      phosphonooxy-2,2,6,6-tetramethylpiperidine (PP-H) for the detection of reactive
      oxidant species as a diagnostic tool for extracellular inflammation-induced
      oxidative stress. We used inflammation induced by a bacterial endotoxin
      lipopolysaccharide (LPS) as a model. ROS formation was tested in cultured
      macrophages, in blood and in vivo. PP-H reacts with reactive oxidant species
      generating the stable nitroxide radical 4-phosphonooxy-TEMPO. It was shown that a
      5-h treatment of macrophages with LPS (1 microg/ml) leads to a threefold increase
      in superoxide formation as demonstrated using superoxide dismutase. Formation of
      reactive oxidant species 5 h after LPS (1 mg/kg) treatment of Fischer rats was
      analyzed in arterial blood; formation of reactive oxidant species in LPS-treated
      animals increased by a factor of 2.2 and was dependent upon the LPS dose.
      Diphenyleneiodonium (0.1 mM) inhibited formation of LPS-stimulated reactive
      oxidant species by 80%. We suggest that this test could be used as a noninvasive
      diagnostic tool for inflammation-induced oxidative stress.

PMID- 12051667
TI  - The inhibition of poly(ADP-ribose) polymerase enhances growth rates of ataxia
      telangiectasia cells.
AB  - Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme which is activated in
      response to genotoxic insults by binding damaged DNA and attaching polymers of
      ADP-ribose to nuclear proteins at the expense of its substrate NAD+. In persons
      affected with ataxia telangiectasia (A-T), associated mutations in the ataxia
      telangiectasia mutated gene render cells unable to cope with the genotoxic
      stresses from ionizing radiation and oxidative damage, thus resulting in a higher
      concentration of unrepaired DNA damage and the activation of PARP in an
      uncontrolled manner. In primary A-T fibroblasts, we observed a 58-96% increase in
      PARP activity and a concomitant loss of cellular NAD+ and ATP content. PARP
      protein by Western blot analysis increased only slightly in these cells,
      supporting the observation that the steady state levels of DNA damage is higher
      in A-T cells than in normals. When treated with PARP inhibitors 3-aminobenzamide
      or 1,5-dihydroisoquinoline, cellular growth rates reached those observed in
      normal fibroblast cultures. The improvement of cellular growth and NAD+ levels in
      A-T cells with PARP inhibition suggests that the cellular metabolic status of A-T
      cells is compromised and the inhibition of PARP may relieve some of the drain on
      cellular pyridine nucleotides and ATP. Thus, therapy utilizing PARP inhibitors
      may provide a benefit for individuals affected with A-T.

PMID- 12051669
TI  - Changes in the 31P NMR spectrum of rabbit muscle myosin subfragment 1. MgADP with
      temperature.
AB  - In pioneering studies on the 31P NMR spectra of MgADP bound to the "molecular
      motor" myosin subfragment 1 (S1) in the temperature range of 0 to 25 degrees C,
      Shriver and Sykes [Biochemistry 20 (1981) 2004-2012/6357-6362; Biochemistry 21
      (1982) 3022-3028], proposed that MgADP binds to myosin S1 as a mixture of two
      interconvertible conformers with different chemical shifts for the beta-P
      resonance of the S1-bound MgADP and that the concentrations of these conformers
      are related by an equilibrium constant K(T). Their model implied that the
      weighted average of the chemical shifts of the beta-P(MgADP) for S1-bound MgADP
      asymptotically approaches a high temperature limit. Here, and in our earlier
      paper [K. Konno, K. Ue, M. Khoroshev, H., Martinez, B.D. Ray, M.F. Morales, Proc.
      Natl. Acad. Sci. USA 97 (2000) 1461-1466], we report experimental similarities to
      Shriver and Sykes, but diverge from them (especially at 0 degrees C) in not
      finding two distinct peaks and in finding that the average chemical shift does
      not change with temperature. Our observations can be explained by chemical
      exchange of beta-P(MgADP) of S1-bound MgADP between two nearly energetically
      equivalent environments.

PMID- 12051668
TI  - Construction of a catalytically inactive cholesterol oxidase mutant:
      investigation of the interplay between active site-residues glutamate 361 and
      histidine 447.
AB  - Cholesterol oxidase catalyzes the oxidation of cholesterol to cholest-5-en-3-one
      and its subsequent isomerization into cholest-4-en-3-one. Two active-site
      residues, His447 and Glu361, are important for catalyzing the oxidation and
      isomerization reactions, respectively. Double-mutants were constructed to test
      the interplay between these residues in catalysis. We observed that the k(cat) of
      oxidation for the H447Q/E361Q mutant was 3-fold less than that for H447Q and that
      the k(cat) of oxidation for the H447E/E361Q mutant was 10-fold slower than that
      for H447E. Because both doubles-mutants do not have a carboxylate at position
      361, they do not catalyze isomerization of the reaction intermediate cholest-5-en
      3-one to cholest-4-en-3-one. These results suggest that Glu361 can compensate for
      the loss of histidine at position 447 by acting as a general base catalyst for
      oxidation of cholesterol. Importantly, the construction of the double-mutant
      H447E/E361Q yields an enzyme that is 31,000-fold slower than wild type in k(cat)
      for oxidation. The H447E/E361Q mutant is folded like native enzyme and still
      associates with model membranes. Thus, this mutant may be used to study the
      effects of membrane binding in the absence of catalytic activity. It is
      demonstrated that in assays with caveolae membrane fractions, the wild-type
      enzyme uncouples platelet-derived growth factor receptor beta (PDGFRbeta)
      autophosphorylation from tyrosine phosphorylation of neighboring proteins, and
      the H447E/E361Q mutant does not. Thus maintenance of membrane structure by
      cholesterol is important for PDGFRbeta-mediated signaling. The cholesterol
      oxidase mutant probe described will be generally useful for investigating the
      role of membrane structure in signal transduction pathways in addition to the
      PDGFRbeta-dependent pathway tested.

PMID- 12051670
TI  - Interleukin-2 is one of the targets of 1,25-dihydroxyvitamin D3 in the immune
      system.
AB  - Interleukin (IL)-2 knockout (KO) mice, which spontaneously develop symptoms of
      inflammatory bowel disease similar to ulcerative colitis in humans, were made
      vitamin D deficient (D-) or vitamin D sufficient (D+) or were supplemented with
      1,25-dihydroxyvitamin D(3) (1,25D3). 1,25-Dihydroxyvitamin D3 supplementation,
      but not vitamin D supplementation, reduced the early mortality of IL-2 KO mice.
      However, colitis severity was not different in D-, D+, or 1,25D3 IL-2 KO mice.
      Cells from D- IL-2 KO mice produced more interferon (IFN)-gamma than cells from
      all other mice. Con A-induced proliferation was upregulated in IL-2 KO mice and
      downregulated in wildtype (WT) mice fed 1,25D3. All other measured immune
      responses in cells from IL-2 KO mice were unchanged by vitamin D status. In vitro
      addition of 1,25-dihydroxyvitamin D3 significantly reduced the production of IL
      10 and IFN-gamma in cells from D- and D+ WT mice. Conversely, IFN-gamma and IL-10
      production in cells from IL-2 KO mice were refractory to in vitro 1,25
      dihydroxyvitamin D3 treatments. In the absence of IL-2, vitamin D was ineffective
      for suppressing colitis and ineffective for the in vitro downregulation of IL-10
      or IFN-gamma production. One target of 1,25-dihydroxyvitamin D3 in the immune
      system is the IL-2 gene.

PMID- 12051671
TI  - Nitric oxide and fusion with prostasomes increase cytosolic calcium in
      progesterone-stimulated sperm.
AB  - Spermatozoa must undergo a number of reactions before they are able to fertilize
      the oocyte. Among these is the acrosome reaction, which is related to an increase
      in cytosolic Ca2+ concentration ([Ca2+]i). It has been reported in the literature
      that progesterone may achieve this effect through the intervention of
      extragenomic receptors. Nitric oxide (NO) has been reported to affect
      spermatozoa; the nature of the effect depends on the concentration of the
      radical. In a previous paper, we reported that the fusion of spermatozoa with
      prostasomes may also produce a transient increase in spermatozoa [Ca2+]i; in
      addition, this phenomenon causes a long-lasting effect that influences the action
      of progesterone. In this paper, we test the effects of a NO donor (CysNO) and of
      fusion of the prostasome to spermatozoa on progesterone-induced [Ca2+]i increase.
      No effect at all was noticed in the absence of progesterone stimulation. In the
      presence of the hormone, both CysNO and fusion increased the progesterone effect.
      This phenomenon was much more evident if the two treatments were used together.
      We conclude that both NO and fusion with prostasomes act on the progesterone
      dependent pathway additively. Probably the effects are independent.

PMID- 12051673
TI  - Enhancement of lysosomal proton permeability induced by photooxidation of
      membrane thiol groups.
AB  - Effects of photooxidation of membrane thiol groups on lysosomal proton
      permeability were studied by measuring intralysosomal pH with fluorescein
      isothiocyanate-dextran and monitoring proton leakage with p-nitrophenol.
      Methylene blue-mediated photooxidation of lysosomes decreased their membrane
      thiol groups and produced cross-linking of the membrane proteins, which was
      established by the measurement of residual membrane thiol groups with 5,5'-dithio
      bis(2-nitrobenzoic acid) and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, respectively. The cross-linking of proteins could be abolished
      by subsequent treatment of the photodamaged lysosomes with dithiothreitol,
      indicating that the proteins were linked via disulfide bonds. In addition, the
      photodamage of lysosomes raised the intralysosomal pH and caused leakage of the
      lysosomal protons, which could also be reversed by subsequent dithiothreitol
      treatment. This indicates that lysosomal proton permeability can be increased by
      photooxidation of the membrane thiol groups and recovered to the normal level by
      reduction of the groups.

PMID- 12051672
TI  - Role of acetyl-coenzyme A synthetase in leaves of Arabidopsis thaliana.
AB  - Acetyl-coenzyme A synthetase (ACS) is a plastidic enzyme that forms acetyl
      coenzyme A (acetyl-CoA) from acetate and coenzyme A using the energy from ATP.
      Traditionally it has been thought to be the major source for the production of
      acetyl-CoA destined for fatty acid formation. Recent work suggested that the
      accumulation of lipids in developing Arabidopsis seeds was more closely
      correlated with the expression of pyruvate dehydrogenase complex than with the
      expression of ACS, suggesting that most of the carbon for fatty acid formation in
      the plastids of seeds comes from pyruvate rather than from acetate. To explore
      the role of this enzyme, Arabidopsis plants with altered amounts of ACS were
      generated by overexpressing its cDNA in either the sense or the antisense
      configuration. The resulting plants had in vitro enzyme activities that ranged
      from about 5% to over 400% of wild-type levels. The rate of [1-14C]acetate
      conversion into fatty acids was closely related to the in vitro ACS activity,
      showing that the amount of enzyme clearly limited the capacity of leaves to
      convert exogenous acetate to fatty acids. There was, however, no relationship
      between the ACS level and the capacity of the plants to incorporate 14CO2 into
      14C-labeled fatty acids. These data strongly support the idea that, although
      plants can convert acetate into fatty acids, relatively little carbon moves
      through this pathway under normal conditions.

PMID- 12051674
TI  - Activation of microsomal epoxide hydrolase by interaction with cytochromes P450:
      kinetic analysis of the association and substrate-specific activation of epoxide
      hydrolase function.
AB  - The kinetics of the association between cytochrome P450 (P450) and microsomal
      epoxide hydrolase (mEH) was studied by means of resonant mirror based on the
      principle of surface plasmon resonance. The dissociation equilibrium constants
      (K(D)) for the affinity of P450 enzymes for mEH were estimated by resonant mirror
      using an optical biosensor cell covalently bound to rat mEH. Comparable K(D)
      values were obtained for CYP1A1 and 2B1, and these were greater by one order of
      magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on
      the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and
      benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of
      P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A,
      2B, 2C, and 3A subfamilies. In agreement with the association affinity determined
      by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide
      hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only
      CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1)
      many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a
      greater role in the association/activation of mEH and (3) the P450-mediated
      activation of mEH depends upon the substrate of mEH.

PMID- 12051676
TI  - Isolation and characterization of a UDP-glucuronosyltransferase (UGT1A01) cloned
      from female rhesus monkey.
AB  - An isoform (rhesus UGT1A01) orthologus to the human UGT1A1 was cloned and
      sequenced from female rhesus monkey liver cDNA using primers designed from the
      human nucleotide sequences. Open reading frame analysis of the PCR-generated
      product encodes a 533-amino acid protein with a proposed 27-residue signal
      peptide. Nucleotide sequence comparison of rhesus UGT1A01 to other rhesus UGT1A
      isoforms detected a single-transition mutation at nucleotide 1520 (T-->C),
      resulting in a neutral F to S substitution at position 507. Rhesus UGT1A01 was
      greater than 99 and 95% identical to cynomolgus UGT1A01 and human UGT1A1,
      respectively. The rhesus UGT1A01 was expressed in HK-293 cells for functional
      analysis. Catalytic activity of UGT1A01 was determined with 7-hydroxy-4
      (trifluoromethyl)-coumarin and more specific human UGT1A1 substrates (1-naphthol,
      beta-estradiol, 17 alpha-ethinylestradiol, and bilirubin). Expression of UGT1A01
      protein was also detected by a Western blot utilizing a polyclonal antibody
      developed against the human UGT1A family.

PMID- 12051675
TI  - Covalent reactivity of phosphonate monophenyl esters with serine proteinases: an
      overlooked feature of presumed transition state analogs.
AB  - Phosphonate monoesters have been assumed to serve as noncovalent transition state
      analogs for enzymes capable of catalyzing transacylation reactions. Here, we
      present evidence for the covalent reaction of certain serine proteinases and
      peptidase antibody fragments with monophenyl amino(4
      amidinophenyl)methanephosphonate derivatives. Stable adducts of the N
      biotinylated monophenyl ester with trypsin and antibody fragments were evident
      under conditions that disrupt noncovalent interactions. The reaction was
      inhibited by the active-site-directed reagent diisopropyl fluorophosphate. Mass
      spectrometry of the fragments from monoester-labeled trypsin indicated
      phosphonylation of the active site. Irreversible inhibition of trypsin- and
      thrombin-catalyzed hydrolysis of model substrates was observed. Kinetic analysis
      of inactivation of trypsin by the N-benzyloxycarbonylated monoester suggested
      that the first-order rate constant for formation of covalent monoester adducts is
      comparable to that of the diester adducts (0.47 vs 2.0 min(-1)). These
      observations suggest that the covalent reactivity of phosphonate monoesters
      contributes to their interactions with serine proteinases, including certain
      proteolytic antibodies.

PMID- 12051677
TI  - The 4-oxalocrotonate tautomerase family of enzymes: how nature makes new enzymes
      using a beta-alpha-beta structural motif.
AB  - 4-Oxalocrotonate tautomerase (4-OT) catalyzes the isomerization of beta,gamma
      unsaturated enones to their alpha,beta-isomers. The enzyme is part of a plasmid
      encoded pathway, which enables bacteria harboring the plasmid to use various
      aromatic hydrocarbons as their sole sources of carbon and energy. Among
      isomerases and enzymes in general, 4-OT is unusual for two reasons: it has one of
      the smallest known monomer sizes (62 amino acids) and the amino-terminal proline
      functions as the catalytic base. In addition to Pro-1, three other residues (Arg
      11, Arg-39, and Phe-50) have been identified as critical catalytic residues by
      kinetic analysis, site-directed mutagenesis, chemical synthesis, NMR, and
      crystallographic studies. Arginine-39 functions as the general acid catalyst
      (assisted by an ordered water molecule) in the reaction while Arg-11 plays a role
      in substrate binding and facilitates catalysis by acting as an electron sink.
      Finally, the hydrophobic nature of the active site, which lowers the pK(a) of Pro
      1 to approximately 6.4 and provides a favorable environment for catalysis, is
      largely maintained by Phe-50. 4-OT is also the title enzyme of the 4-OT family of
      enzymes. The chromosomal homologues in this family are composed of monomers
      ranging in size from 61 to 79 amino acids, which code a beta-alpha-beta
      structural motif. The homologues all retain Pro-1 and generally have an aromatic
      or hydrophobic amino acid at the Phe-50 position. Characterization of
      representative members has uncovered mechanistic and structural diversity. A new
      activity, a trans-3-chloroacrylic acid dehalogenase, has been identified in
      addition to the previously known tautomerase and isomerase activities. Two new
      structures have also been found, along with the 4-OT hexamer. The dehalogenase
      functions as a heterohexamer while the Escherichia coli homologue, designated
      YdcE, functions as a dimer. Moreover, both 4-OT and the Bacillus subtilis
      homologue, designated YwhB, exhibit low-level dehalogenase activity.
      Amplification of this activity could have produced the full-fledged dehalogenase.
      The sum of these observations indicates that Nature uses the beta-alpha-beta
      structural motif as a building block in a variety of manners to create new
      enzymes.

PMID- 12051679
TI  - Analysis of the roles of amino acid residues in the flavoprotein tryptophan 2
      monooxygenase modified by 2-oxo-3-pentynoate: characterization of His338, Cys339,
      and Cys511 mutant enzymes.
AB  - The flavoprotein tryptophan 2-monooxygenase catalyzes the oxidative
      decarboxylation of tryptophan to indoleacetamide. His338, Cys339, and Cys511 of
      the Pseudomonas savastanoi enzyme were previously identified as possible active
      site residues by modification with 2-oxo-3-pentynoate ([G. Gadda, L.J. Dangott,
      W.H. Johnson Jr., C.P. Whitman, P.F. Fitzpatrick, Biochemistry 38 (1999) 5822
      5828]). The H338N, C339A, and C511S enzymes have been characterized to determine
      the roles of these residues in catalysis. The steady-state kinetic parameters
      with both tryptophan and methionine decrease only slightly in the case of the
      H338N and C339A enzymes; the decrease in activity is greater for the C511S
      enzyme. Only in the case of the C511S enzyme do deuterium kinetic isotope effects
      on kinetic parameters indicate a significant change in catalytic rates. The
      structural bases for the effects of the mutations can be interpreted by
      identification of L-amino acid oxidase and tryptophan monooxygenase as homologous
      proteins.

PMID- 12051678
TI  - Biochemical and preliminary crystallographic characterization of the vitamin D
      sterol- and actin-binding by human vitamin D-binding protein.
AB  - Vitamin D-binding protein (DBP), a multi-functional serum glycoprotein, has a
      triple-domain modular structure. Mutation of Trp145 (in Domain I) to Ser
      decreased 25-OH-D(3)-binding by 80%. Furthermore, recombinant Domain I (1-203)
      and Domain I + II (1-330) showed specific and strong binding for 25-OH-D(3), but
      Domain III (375-427) did not, suggesting that only Domains I and II might be
      required for vitamin D sterol-binding. Past studies have suggested that Domain
      III is independently capable of binding G-actin. We exploited this apparently
      independent ligand-binding property of DBP to purify DBP-actin complex from human
      serum and rabbit muscle actin by 25-OH-D(3) affinity chromatography. Competitive
      (3)H-25-OH-D(3) binding curves for native DBP and DBP-actin complex were almost
      identical, further suggesting that vitamin D sterol- and actin-binding activities
      by DBP might be largely independent of each other. Trypsin treatment of DBP
      produced a prominent 25 kDa band (Domain I, minus 5 amino acids in N-terminus),
      while actin was completely fragmented by such treatment. In contrast, tryptic
      digestion of purified DBP-actin complex showed two prominent bands, 52 (DBP,
      minus 5 amino acids in the N-terminus) and 34 kDa (actin, starting with amino
      acid position 69) indicating that DBP, particularly its Domains II and III were
      protected from trypsin cleavage upon actin-binding. Similarly, actin, except its
      N-terminus, was also protected from tryptic digestion when complexed with DBP.
      These results provided the basis for our studies to crystallize DBP-actin
      complex, which produced a 2.5 A crystal, primitive orthorhombic with unit cell
      dimensions a=80.2A, b=87.3A, and c=159.6A, P2(1)2(1)2(1) space group, V(m)=2.9.
      Soaking of crystals of actin-DBP in crystallization buffer containing various
      concentrations of 25-OH-D(3) resulted in cracking of the crystal, which was
      probably a reflection of a ligand-induced conformational change in the complex,
      disrupting crystal contacts. In conclusion, we have provided data to suggest that
      although binding of 25-OH-D(3) to DBP might result in discrete conformational
      changes in the holo-protein to influence actin-binding, these binding processes
      are largely independent of each other in solution.

PMID- 12051680
TI  - Renal excretion of 8-oxo-7,8-dihydro-2(')-deoxyguanosine: degradation rates of
      RNA and metabolic rate in humans.
AB  - Renally excreted 8-oxo-7,8-dihydro-2(')-deoxyguanosine (oxo(8)dG) is a potential
      marker of oxidative DNA damage by reactive oxygen species. Whole-body degradation
      rates of t- and rRNA are potential indicators of the resting metabolic rate
      (RMR). Excretion rates of oxo(8)dG and degradation rates of t- and rRNA were
      determined in healthy non-smoking adults and children. RMR (indirect calorimetry;
      14 children, 16 adults), total energy expenditure (TEE; doubly labelled water
      technique; 4 children, 6 adults), and lean body mass (LBM; dual-energy X-ray
      absorptiometry; 14 children, 16 adults) were also measured. Degradation of t- and
      rRNA (micromol/d/kg LBM; 4 children, 6 adults) was highly correlated with RMR
      (kJ/d/kg LBM), r=0.867 (p<0.005) and 0.959 (p<0.001), respectively. Excretion of
      oxo(8)dG (pmol/d/kg LBM; 14 children, 16 adults) was not significantly correlated
      with RMR (p>0.05). Neither excretion of oxo(8)dG nor degradation of RNA was
      significantly correlated with TEE (kJ/d/ kg LBM) (p>0.05). In healthy subjects
      further factors, other than the metabolic rate, seem to influence the excretion
      rate of oxo(8)dG. The degradation rates of t- and rRNA seem to be appropriate
      indicators of the RMR.

PMID- 12051681
TI  - Synthesis and bacterial expression of a gene encoding the heme domain of
      assimilatory nitrate reductase.
AB  - Assimilatory NADH:nitrate reductase (EC 1.6.6.1), a complex Mo-pterin-,
      cytochrome b(557)-, and FAD-containing protein, catalyzes the regulated and rate
      limiting step in the utilization of inorganic nitrogen by higher plants. A codon
      optimized gene has been synthesized for expression of the central cytochrome
      b(557)-containing fragment, corresponding to residues A542-E658, of spinach
      assimilatory nitrate reductase. While expression of the full-length synthetic
      gene in Escherichia coli did not result in significant heme domain production,
      expression of a Y647* truncated form resulted in substantial heme domain
      production as evidenced by the generation of "pink" cells. The histidine-tagged
      heme domain was purified to homogeneity using a combination of NTA-agarose and
      size-exclusion FPLC, resulting in a single protein band following SDS-PAGE
      analysis with a molecular mass of approximately 13 kDa. MALDI-TOF mass
      spectrometry yielded an m/z ratio of 12,435 and confirmed the presence of the
      heme prosthetic group (m/z=622) while cofactor analysis indicated a 1:1 heme to
      protein stoichiometry. The oxidized heme domain exhibited spectroscopic
      properties typical of a b-type cytochrome with a visible Soret maximum at 413 nm
      together with epr g-values of 2.98, 2.26, and 1.49, consistent with low-spin bis
      histidyl coordination. Oxidation-reduction titrations of the heme domain
      indicated a standard midpoint potential (E(o)') of -118 mV. The isolated heme
      domain formed a 1:1 complex with cytochrome c with a K(A) of 7 microM
      (micro=0.007) and reconstituted NADH:cytochrome c reductase activity in the
      presence of a recombinant form of the spinach nitrate reductase flavin domain,
      yielding a k(cat) of 1.4 s(-1) and a K(m app) for cytochrome c of 9 microM. These
      results indicate the efficient expression of a recombinant form of the heme
      domain of spinach nitrate reductase that retained the spectroscopic and
      thermodynamic properties characteristic of the corresponding domain in the native
      spinach enzyme.

PMID- 12051682
TI  - 2-Arachidonoyl-sn-glycero-3-phosphate, an arachidonic acid-containing
      lysophosphatidic acid: occurrence and rapid enzymatic conversion to 2
      arachidonoyl-sn-glycerol, a cannabinoid receptor ligand, in rat brain.
AB  - A substantial amount of lysophosphatidic acid (LPA) (15.66 nmol/g tissue) was
      found to occur in the brain isolated from rats killed in liquid nitrogen. We
      found that a significant portion of brain LPA was accounted for by the
      arachidonic acid-containing species (5.4%). We obtained evidence that both 2
      arachidonoyl species and 1-arachidonoyl species of LPA are present. The
      occurrence of 2-arachidonoyl LPA in the brain (0.53 nmol/g tissue) is a notable
      observation, because of its structural resemblance to 2-arachidonoyl-sn-glycerol
      (2-AG), an endogenous cannabinoid receptor ligand. We then examined the
      biological activity of 2-arachidonoyl LPA and compared it with that of 2-AG using
      neuroblastoma x glioma hybrid NG108-15 cells which express both the LPA receptor
      and cannabinoid CB1 receptor. We found that 2-arachidonoyl LPA interacts with the
      LPA receptor(s) to elicit the elevation of intracellular free Ca(2+)
      concentrations, whereas 2-AG interacts exclusively with the cannabinoid CB1
      receptor. Next, we examined the possible metabolic relationship between 2
      arachidonoyl LPA and 2-AG and obtained clear evidence that rapid enzymatic
      conversion of 2-arachidonoyl LPA to 2-AG took place in the brain homogenate. It
      is noteworthy that two types of endogenous ligands, that interact with different
      types of receptors, are closely related metabolically and rapidly interconvert.

PMID- 12051683
TI  - The carbon monoxide derivative of human hemoglobin carrying the double mutation
      LeuB10-->Tyr and HisE7-->Gln on alpha and beta chains probed by infrared
      spectroscopy.
AB  - The fine structural properties of the distal heme pocket have been probed by
      infrared spectroscopy of ferrous carbon monoxy human hemoglobin mutants carrying
      the mutations LeuB10-->Tyr and HisE7-->Gln on the alpha, beta, and both chains,
      respectively. The stretching frequency of iron-bound carbon monoxide occurs as a
      single broad band around 1943 cm(-1) in both the alpha and the beta mutated
      chains. Such a frequency value indicates that no direct hydrogen bonding exists
      between the bound CO molecule and the TyrB10 phenolic oxygen, at variance with
      other naturally occurring TyrB10, GlnE7 nonvertebrate hemoglobins. The rates of
      carbon monoxide release have been determined for the first time by a Fourier
      transform infrared spectroscopy stopped-flow technique that allowed us to single
      out the heterogeneity in the kinetics of CO release in the alpha and beta chains
      for the mutated proteins and for native HbA. The rates of CO release are 15- to
      20-fold faster for the mutated alpha or beta chains with respect to the native
      ones consistent with the lack of distal stabilization on the iron-bound CO
      molecule. The present results demonstrate that residues in key topological
      positions (namely E7 and B10) for the distal steric control of the iron-bound
      ligand are not interchangeable among hemoglobins from different species.

PMID- 12051684
TI  - Isolation and characterization of an acetyl group-recognizing agglutinin from the
      serum of the Indian white shrimp Fenneropenaeus indicus.
AB  - A natural agglutinin from the serum of the Indian white shrimp Fenneropenaeus
      (Penaeus) indicus was purified to electrophoretic homogeneity by a single-step
      affinity chromatography on N-acetylglucosamine-Sepharose 6B. The expression of
      hemagglutinating (HA) activity of F. indicus agglutinin (FIA) was independent of
      the presence of divalent cations and insensitive to their chelators. FIA gave a
      single symmetrical peak in its native form with a molecular mass estimate of 200
      kDa on gel filtration in HPLC, and SDS-PAGE under reducing conditions revealed
      that it is a homo-oligomer of a 27-kDa subunit protein. The pattern of reactivity
      of FIA against anti-FIA rabbit serum in immunodiffusion and immunoelectrophoretic
      analysis provided additional evidence for its purity and homogeneity. HA
      inhibition studies documented exclusive specificity of FIA for acetyl groups in
      carbohydrates independently of the presence of these groups at the C-2 or C-5
      position and its stereochemical arrangement in the axial or equatorial
      orientation. The unique ability of FIA to recognize acetyl groups was also
      explicitly demonstrated with sialo- and asialo-glycoproteins. Strikingly, FIA
      also interacted equally with amino acids and chemicals containing acetyl groups,
      thereby unambiguously demonstrating the exquisite specificity of FIA for an
      acetyl group, irrespective of the presence of this group in carbohydrate or
      noncarbohydrate ligands. The susceptibility of HA activity of FIA to inhibition
      by lipopolysaccharides from diverse gram-negative bacteria as well as its ability
      to selectively agglutinate several bacterial species isolated from infected
      shrimps implicate a potential role of this humoral agglutinin of F. indicus in
      the host immunodefense reactions against microbial invaders.

PMID- 12051685
TI  - Rapamycin induces binding activity to the terminal oligopyrimidine tract of
      ribosomal protein mRNA in rats.
AB  - The immunosuppressant rapamycin selectively suppresses the translation of mRNAs
      containing a terminal oligopyrimidine (TOP) tract adjacent to the cap structure.
      trans-Acting factors that bind to the 5'-untranslated region (5'-UTR) of TOP
      mRNAs may be involved in selective translational repression. Some of these
      factors are regulated by rapamycin-responsive signaling pathways. To identify
      candidates for the selective trans-acting factor, we examined whether
      administration of rapamycin alters the binding activity of proteins that bind to
      RNA containing the TOP element of mouse ribosomal protein (r-protein) L32 mRNA.
      Preadministration with Freund's complete adjuvant (FCA) prior to rapamycin
      treatment resulted in increased translational efficiency of r-protein L32 mRNA in
      submaxillary lymph node (SLN; 2.3-fold), thymus (1.5-fold), and parotid gland
      (PG; 1.6-fold). Translation of r-protein L32 or elongation factor 1A mRNAs in SLN
      and PG from FCA-pretreated rats were sensitive to rapamycin administration and
      the binding ability of p56 was generally increased in extracts from these
      tissues. On the other hand, in thymus, rapamycin had no effect on the
      translational efficiency of TOP mRNAs and no p56 binding was detected in the
      extracts from FCA-pretreated animals. Coadministration of FK506, another
      immunosuppressive macrolide, increased the p56 TOP-RNA-binding activity and
      induced selective translational repression of TOP mRNAs in a dose-dependent
      manner, even in thymus. These findings indicate that p56 is a plausible candidate
      for the trans-acting factor responsible for regulating the translation of TOP
      mRNA by a rapamycin-sensitive pathway and that TOP mRNA translational regulation
      may be responsible for the tissue specificity of rapamycin.

PMID- 12051686
TI  - Phosphatidylinositide 3-kinase regulates angiotensin II-induced cytosolic
      phospholipase A2 activity and growth in vascular smooth muscle cells.
AB  - Angiotensin (Ang) II via the AT(1) receptor acts as a mitogen in vascular smooth
      muscle cells (VSMC) through stimulation of multiple signaling mechanisms,
      including tyrosine kinases and mitogen-activated protein kinase (MAPK). In
      addition, cytosolic phospholipase A(2)(cPLA(2))-dependent release of arachidonic
      acid (AA) is linked to VSMC growth and we have reported that Ang II stimulates
      cPLA(2) activity via the AT(1) receptor. The coupling of Ang II to the activation
      of cPLA(2) appears to involve mechanisms both upstream and downstream of MAPK
      such that AA stimulates MAPK activity which phosphorylates cPLA(2) to further
      enhance AA release. However, the upstream mechanisms responsible for activation
      of cPLA(2) are not well-defined. One possibility includes phosphatidylinositide 3
      kinase (PI3K), since PI3K has been reported to participate in the upstream
      signaling events linked to activation of MAPK. However, it is not known whether
      PI3K is involved in the Ang II-induced activation of cPLA(2) or if this mechanism
      is associated with the Ang II-mediated growth of VSMC. Therefore, we used
      cultured rat VSMC to examine the role of PI3K in the Ang II-dependent
      phosphorylation of cPLA(2), release of AA, and growth induced by Ang II. Exposure
      of VSMC to Ang II (100 nM) increased [(3)H]thymidine incorporation, cell number,
      and the release of [(3)H]AA. Also, using Western analysis, Ang II increased the
      phosphorylation of MAPK and cPLA(2) which were blocked by the MAPK kinase
      inhibitor PD98059 (10 microM/L). Similarly, the PI3K inhibitor LY294002 (10
      microM/L) abolished the Ang II-mediated increase in MAPK phosphorylation, as well
      as phosphoserine-PLA(2). Further, inhibition of PI3K blocked the Ang II-induced
      release of AA and VSMC mitogenesis. However, exogenous AA was able to restore
      VSMC growth in the presence of LY294002, as well as reverse the inhibition of
      MAPK and cPLA(2) phosphorylation by LY294002. Thus, it appears from these data
      that Ang II stimulates the PI3K-sensitive release of AA which stimulates MAPK to
      phosphorylate cPLA(2) and enhance AA release. This mechanism may play an
      important role in the Ang II-induced growth of VSMC.

PMID- 12051687
TI  - Mutation of an essential glutamate residue in folylpolyglutamate synthetase and
      activation of the enzyme by pteroate binding.
AB  - Site-directed mutagenesis was performed on Glu143, an essential amino acid in
      Lactobacillus casei folylpolyglutamate synthetase (FPGS) and the structurally
      equivalent residue, Glu146, in Escherichia coli FPGS. Glu143 is positioned near
      the P-loop and interacts with the Mg(2+) of Mg NTP-binding proteins. We have
      solved the structure of the E143A mutant of L. casei FPGS in the presence of
      AMPPCP and Mg(2+). The structure showed a water molecule at the place where
      Mg(2+) bound to the wild type enzyme. Mutant proteins E143A, and even E143D and
      E143Q with conservative mutations, lacked enzyme activity and failed to
      complement the methionine auxotrophy of the E. coli folC mutant SF4, showing that
      Glu143 is an essential residue. Both the L. casei and the E. coli FPGS mutant
      proteins bound methylene-tetrahydrofolate diglutamate and dihydropteroate
      normally. The E. coli E146Q mutant FPGS bound ADP with the same affinity as the
      wild type enzyme but bound ATP with much lower affinity and had higher ATPase
      activity than the wild type enzyme. The mutant enzyme was defective in forming
      the acyl-phosphate reaction intermediate from ATP and dihydropteroate. The E.
      coli FPGS requires activation by dihydropteroate or tetrahydrofolate binding to
      allow full activity. In the absence of a pteroate substrate, only 30% of the
      total enzyme binds ATP. We suggest that dihydropteroate causes a conformational
      change to allow increased ATP binding. The mutant enzyme was similarly activated
      by dihydropteroate resulting in increased ADP binding.

PMID- 12051688
TI  - Manganese supplementation relieves the phenotypic deficits seen in superoxide
      dismutase-null Escherichia coli.
AB  - Escherichia coli, lacking cytoplasmic superoxide dismutases, exhibits a variety
      of oxygen-dependent phenotypic deficits. Enrichment of the growth medium with
      Mn(II) relieved those deficits. Extracts of cells grown on Mn(II)-rich medium
      exhibited superoxide dismutase-like activity that was due partially to low
      molecular-weight and partially to high-molecular-weight complexes. The high
      molecular-weight activity was sensitive to proteolysis. Hence this activity is
      likely associated with low-affinity binding of Mn to proteins.

PMID- 12051689
TI  - Effect of pyridoxamine on chemical modification of proteins by carbonyls in
      diabetic rats: characterization of a major product from the reaction of
      pyridoxamine and methylglyoxal.
AB  - Advanced glycation end products (AGEs) from the Maillard reaction contribute to
      protein aging and the pathogenesis of age- and diabetes-associated complications.
      The alpha-dicarbonyl compound methylglyoxal (MG) is an important intermediate in
      AGE synthesis. Recent studies suggest that pyridoxamine inhibits formation of
      advanced glycation and lipoxidation products. We wanted to determine if
      pyridoxamine could inhibit MG-mediated Maillard reactions and thereby prevent AGE
      formation. When lens proteins were incubated with MG at 37 degrees C, pH 7.4, we
      found that pyridoxamine inhibits formation of methylglyoxal-derived AGEs
      concentration dependently. Pyridoxamine reduces MG levels in red blood cells and
      plasma and blocks formation of methylglyoxal-lysine dimer in plasma proteins from
      diabetic rats and it prevents pentosidine (an AGE derived from sugars) from
      forming in plasma proteins. Pyridoxamine also decreases formation of protein
      carbonyls and thiobarbituric-acid-reactive substances in plasma proteins from
      diabetic rats. Pyridoxamine treatment did not restore erythrocyte glutathione
      (which was reduced by almost half) in diabetic animals, but it enhanced
      erythrocyte glyoxalase I activity. We isolated a major product of the reaction
      between MG and pyridoxamine and identified it as methylglyoxal-pyridoxamine
      dimer. Our studies show that pyridoxamine reduces oxidative stress and AGE
      formation. We suspect that a direct interaction of pyridoxamine with MG partly
      accounts for AGE inhibition.

PMID- 12051690
TI  - Alteration of product formation by directed mutagenesis and truncation of the
      multiple-product sesquiterpene synthases delta-selinene synthase and gamma
      humulene synthase.
AB  - Two recombinant sesquiterpene synthases from grand fir, delta-selinene synthase
      and gamma-humulene synthase, each produce more than 30 sesquiterpene olefins from
      the acyclic precursor farnesyl diphosphate. These enzymes contain a pair of DDxxD
      motifs, on opposite lips of the presumptive active site, which are thought to be
      involved in substrate binding and could promote multiple orientations of the
      substrate alkyl chain from which multiple families of cyclic olefins could
      derive. Mutagenesis of the first aspartate of either DDxxD motif resulted in
      depressed k(cat), with lesser effect on K(m), for delta-selinene synthase and
      afforded a much simpler product spectrum composed largely of monocyclic olefins.
      Identical alterations in gamma-humulene synthase produced similar kinetic effects
      with a simplified product spectrum of mostly acyclic and monocyclic olefins.
      Although impaired in product diversity, none of the mutant synthases lost
      entirely the capacity to generate complex structures. These results confirm the
      catalytic significance of the DDxxD motifs and imply that they also influence
      permitted modes of cyclization. Deletion of an N-terminal arginine pair in delta
      selinene synthase (an element potentially involved in substrate isomerization)
      altered kinetics without substantially altering product outcome. Finally,
      mutation of an active-site tyrosine residue thought to play a role in proton
      exchange had little influence; however, substitution of a nearby active site
      aspartate dramatically altered kinetics and product outcome.

PMID- 12051691
TI  - Lipid metabolism during aging of high-alpha-linolenate-phenotype potato tubers.
AB  - Previous studies demonstrated that high levels of alpha-linolenate in cell
      membranes of potato tubers (achieved by overexpressing fatty acid desaturases)
      enhances lipid peroxidation, oxidative stress, and tuber metabolic rate,
      effectively accelerating the physiological age of tubers. This study details the
      changes in lipid molecular species of microsomal and mitochondrial membranes from
      wild-type (WT) and high-alpha-linolenate tubers during aging. The microsomal and
      mitochondrial polar lipids of high-alpha-linolenate tubers were dominated by
      18:3/18:3 and 16:0/18:3 molecular species. Relative to WT tubers, high-alpha
      linolenate tubers had a substantially higher 16:0/18:n to 18:n/18:n molecular
      species ratio in mitochondria and microsomes, potentially reflecting a
      compensatory response to maintain membrane biophysical properties in the face of
      increased unsaturation. Phosphatidylcholine (PC) and phosphatidylethanolamine
      (PE) accounted for 53 and 37% of polar lipids, respectively, in mitochondria from
      younger WT and high-alpha-linolenate tubers. The relative proportions of these
      phospholipids (PL) did not change during aging of WT tubers. In contrast, PE
      increased to dominate the PL pool of mitochondria during aging of high-alpha
      linolenate tubers. While aging effected an increase in mitochondrial 18:3-bearing
      PCs and PEs in WT tubers, the concentration of 18:3-bearing PCs fell with a
      concomitant increase in 18:3-bearing PEs during aging of high-alpha-linolenate
      tubers. These age- and high-alpha-linolenate-induced changes had no effect on the
      respiration rate and functional integrity of isolated mitochondria. Differential
      increases in the respiration rates of WT and high-alpha-linolenate tubers during
      aging were therefore a consequence of unsaturation-dependent alterations in the
      microenvironments of cells. Microsomal 18:3-bearing PCs, PEs,
      digalactosyldiacylglycerols (DGDG), and monogalactosyldiacylglycerols all
      increased in WT tubers during aging. In contrast, a selective loss of 18:3
      bearing PCs and DGDGs from microsomes of high-alpha-linolenate tubers likely
      reflects a greater susceptibility of membranes to peroxidative catabolism during
      aging. Aging resulted in an increase in sterol/PL ratio in microsomes from WT
      tubers, due primarily to a decline in PL. In high-alpha-linolenate tubers, the
      increase in sterol/PL ratio during aging was due to increases in Delta 5
      avenasterol and stigmasterol, indicating membrane rigidification and likely
      contributing to increased membrane permeability. Age-induced changes in 18:3
      bearing lipids in membranes of transformed tubers are discussed relative to the
      development of oxidative stress and accelerated aging.

PMID- 12051692
TI  - Paraquat detoxicative system in the mouse liver postmitochondrial fraction.
AB  - We examined the paraquat detoxicative system in mouse livers. The survival rate
      of mice receiving 50 mg/kg paraquat was 41% at 7 days and significantly rose to
      88, 64, 69% with pretreatment with phenytoin, phenobarbital, and rifampicin,
      respectively. Phenytoin induced activity in NADPH-cytochrome P450 reductase,
      CYP3A, CYP2B, and CYP2C that was 3 to 4 times higher than that of the controls.
      Phenobarbital induced CYP2B and rifampicin induced CYP3A, respectively, in
      addition to NADPH-cytochrome P450 reductase. 3-Methylcholanthrene did not induce
      these enzymes and did not alter the survival rate. All the mice pretreated with
      CoCl(2) (a CYP synthesis inhibitor) or SKF 525-A (a CYP inhibitor) were dead
      after 5 days, and troleandomycin (a CYP3A-specific inhibitor) also reduced the
      survival rate. When cell homogenates were incubated with paraquat and NADPH,
      paraquat decreased and its metabolic intermediate paraquat-monopyridone was
      formed. Troleandomycin inhibited the decrease in paraquat and increased the
      monopyridone. After making a subfraction of the homogenate, monopyridone was
      produced in the postmicrosomal 105,000g supernatant, but not in the microsomes.
      The pretreatment of mice with phenytoin decreased the monopyridone in the
      postmitochondrial fraction, but did not affect the supernatant. These results
      indicated that paraquat was first metabolized in the postmicrosomal supernatant
      into monopyridone, and that may have been subsequently hydroxylated by the
      microsomes. Repeated intravenous injections of alpha-tocopherol to paraquat
      loaded mice significantly reduced the paraquat mortality and when these mice were
      pretreated with rifampicin, 100% of them survived. These studies demonstrate that
      postmitochondrial fractions play an important role in paraquat detoxication
      metabolism, and that the combination of CYP induction and alpha-tocopherol
      administration is highly useful for the survival of paraquat-exposed mice.

PMID- 12051693
TI  - A truncated splice variant of KCNQ1 cloned from rat heart.
AB  - KCNQ1 encodes a pore-forming subunit of potassium channels. Mutations in this
      gene cause inherited diseases, i.e., Romano-Ward syndrome and Jervell and Lange
      Nielsen syndrome. A truncated isoform of KCNQ1 was reported to be expressed
      physiologically and to suppress a delayed rectifier potassium current dominant
      negatively in human heart. However, it is not known whether this way of
      modulation occurs in other species. We cloned another truncated splice variant of
      KCNQ1 (tr-rKCNQ1) from rat heart. Judging from the deleted sequence of the tr
      rKCNQ1, the genomic structure of rat in this portion might be different from
      those of human and mouse. Otherwise, an unknown exon might exist. RT-PCR analysis
      demonstrated that the tr-rKCNQ1 was expressed in fetal and neonatal hearts. When
      this gene was expressed along with a full-length KCNQ1, it suppressed potassium
      currents, whether a regulatory subunit minK was co-expressed or not.

PMID- 12051695
TI  - Amphipathic helical behavior of the third repeat fragment in the tau microtubule
      binding domain, studied by (1)H NMR spectroscopy.
AB  - The third repeat fragment (3MBD, 31 residues) in the four-repeat microtubule
      binding domain of water-soluble tau protein has been considered to be responsible
      for the formation of the neuropathological filament. To clarify the structural
      requisite of 3MBD for the filamentous assembly, the solution structures in water
      and trifluoroethanol (TFE) were investigated by a combination of two-dimensional
      (1)H-NMR measurements and molecular modeling calculations. All protons were
      assigned by various 2D NMR spectral measurements. The NOE patterns characteristic
      to the typical helical structure were observed in TFE solution, as was expected
      from the CD spectra. Using 273 NOE and 23 (3)J(NHC(alpha)H) data, possible 3D
      structures were generated by the dynamical simulated annealing method. The
      constructed NMR conformers showed that the N-terminal Val1-Lys6 and Leu10-Leu20
      fragments form the well-refined extended and alpha-helical structures,
      respectively, whereas the C-terminal moiety is highly flexible. Interestingly,
      the helical structure showed amphipathic distribution of the respective side
      chains. This amphipathic behavior of the 3MBD structure would be necessary for
      self-associating into a helical filament of the tau MBD domain, because such a
      filament is stabilized by the alternating hydrophilic and hydrophobic
      interactions between the 3MBD fragments.

PMID- 12051694
TI  - Novel missense mutations in red/green opsin genes in congenital color-vision
      deficiencies.
AB  - The DNAs from 217 Japanese males with congenital red/green color-vision
      deficiencies were analyzed. Twenty-three subjects had the normal genotype of a
      single red gene, followed by a green gene. Four of the 23 were from the 69 protan
      subject group and 19 of the 23 were from the 148 deutan subject group. Three of
      the 23 subjects had missense mutations. The mutation Asn94Lys (AAC-->AAA)
      occurred in the single green gene of a deutan subject (A155). The Arg330Gln (CGA-
      >CAA) mutation was detected in both green genes of another deutan subject (A164).
      The Gly338Glu (GGG-->GAG) mutation occurred in the single red gene of a protan
      subject (A89). Both normal and mutant opsins were expressed in cultured COS-7
      cells and visual pigments were regenerated with 11-cis-retinal. The normal red
      and green opsins showed absorbance spectra with lambda(max) of 560 and 530 nm,
      respectively, but the three mutant opsins had altered spectra. The mutations in
      Asn94Lys and Gly338Glu resulted in no absorbance and the Arg330Gln mutation gave
      a low absorbance spectrum with a lambda(max) of 530 nm. Therefore these three
      mutant opsins are likely to be affected in the folding process, resulting in a
      loss of function as a visual pigment.

PMID- 12051696
TI  - Leptin induces IL-1 receptor antagonist expression in the brain.
AB  - The ob gene product, leptin, is known to be an important circulating signal for
      regulation of food intake and body weight. We report here that peripherally
      applied leptin increased interleukin-1 receptor antagonist (IL-1ra) transcripts
      in the hypothalamus. Interestingly, we observed leptin-induced increase in IL-1ra
      transcripts not only in the hypothalamus but also in other brain regions such as
      the hippocampus, the cortex, the cerebellum, and the brain stem. Moreover, leptin
      applied to the db/db mice, which lack functional Ob-Rb receptor, increased IL-1ra
      mRNA levels in the hyothalamus to a similar extent as in normal mice. These
      results indicate that the leptin-induced IL-1ra expression in the brain may be
      mediated through STAT3 independent mechanisms.

PMID- 12051697
TI  - Disruption in gastric mucin synthesis by Helicobacter pylori lipopolysaccharide
      involves ERK and p38 mitogen-activated protein kinase participation.
AB  - Helicobacter pylori is a primary factor in the etiology of gastric disease, and
      its early pathogenic effects are manifested by up-regulation of inflammatory
      processes and the loss of mucus coat continuity. We investigated the role of
      extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein
      kinase (MAPK) in the disturbances in gastric mucin synthesis and apoptotic
      processes evoked by H. pylori lipopolysaccharide (LPS). Exposure of gastric
      mucosal cells to the LPS led to a dose-dependent decrease (up to 59.5%) in mucin
      synthesis, accompanied by a marked increase in caspase-3 activity and apoptosis.
      Inhibition of ERK with PD98059 accelerated (up to 36.1%) the LPS-induced decrease
      in mucin synthesis, and caused further enhancement in caspase-3 activity and
      apoptosis. Blockade of p38 kinase with SB203580 produced reversal in the LPS
      induced reduction in mucin synthesis, and substantially countered the LPS-induced
      increases in caspas-3 activity and apoptosis. Moreover, inhibition of caspase-3
      blocked the LPS-induced increase in caspse-3 activity and produced an increase in
      mucin synthesis. Thus the detrimental influence of H. pylori LPS on gastric mucin
      synthesis is closely linked to caspase-3 activation and apoptosis, and involves
      ERK and p38 kinase participation.

PMID- 12051698
TI  - Macrophage migration inhibitory factor in drug-induced liver injury: a role in
      susceptibility and stress responsiveness.
AB  - Idiosyncratic drug-induced hepatitis may depend upon many factors including a
      balance between pro- and anti-inflammatory mediator production levels. Using a
      guinea pig model of liver injury induced by bioactivation of the anesthetic drug,
      halothane, we found that toxicity was commensurate with an increase in serum
      macrophage migration inhibitory factor (MIF), a pro-inflammatory signal and
      counter-regulator of glucocorticoids, but only in susceptible animals. The
      pathogenic role of MIF was further investigated using a murine model in which
      liver injury was induced by the reactive metabolite of another drug,
      acetaminophen (APAP). MIF leakage from the liver into the sera preceded peak
      increases in toxicity following APAP administration. MIF null (-/-) mice were
      significantly less susceptible to this toxicity at 8 h. At 48 h following a 300
      mg/kg dose, complete lethality was observed in wild-type mice, while 46% survival
      was noted in MIF-/- mice. The decreased hepatic injury in MIF-/- mice correlated
      with a reduction in mRNA levels of interferon-gamma and a significant increase in
      heat shock protein expression, but was unrelated to the APAP-protein adduct
      formation in the liver. These findings support MIF as a critical pro-toxicant
      signal in drug-induced liver injury with potentially important and novel effects
      on heat shock protein responsiveness.

PMID- 12051699
TI  - Functional analysis of aortic endothelial cells expressing mutant PDGF receptors
      with respect to expression of matrix metalloproteinase-3.
AB  - Platelet-derived growth factor (PDGF) stimulates expression of matrix
      metalloproteinases (MMPs), including stromelysin-1 (MMP-3). Induction of these
      expressions is known to occur during the course of atherosclerosis, tumor
      invasion, and metastasis. We investigated PDGF-alpha receptor (alphaR)- and beta
      receptor (betaR)-mediated signaling pathways for the expression of MMP-3 and
      invasion activity using porcine aortic endothelial (PAE) cells with stable
      expression of normal or mutated PDGF receptors. RT-PCR and Western blot analyses
      revealed that PDGF-BB induces MMP-3 expression in PAE cells that exclusively
      express either the PDGF-alphaR or the -betaR, but not in non-transfected control
      cells. To identify the signals necessary for PDGF receptor-mediated induction of
      MMP-3 expression, several lines of PAE cells expressing mutant PDGF receptors
      were further analyzed. Cells expressing mutant PDGF receptors unable to associate
      with Src or PLCgamma, retained the ability to induce MMP-3 expression as a result
      of PDGF-BB stimulation. However, incubation with PDGF-BB did not induce MMP-3
      expression in cells expressing a mutant PDGF-betaR unable to associate with
      phosphatidylinositol 3(')-kinase (PI3K). LY294002, a PI3K inhibitor, reduced PDGF
      BB-stimulated MMP-3 expression in PAE cells expressing wild-type PDGF receptors.
      In contrast, PDGF-BB induced MMP-3 expression in the presence of U-73122, a
      PLCgamma inhibitor. Moreover, PDGF-BB enhanced the invasiveness of cells
      expressing wild type PDGF-beta receptors, but not of cells expressing mutant PDGF
      betaRs impaired in their ability to associate with PI3K. In light of these
      results, it appears that PDGF-BB is capable of inducing MMP-3 expression through
      both the PDGF-alphaR and the -betaR, and the effects are contributed by the PI3K
      mediated transduction pathways.

PMID- 12051700
TI  - Overexpression of glia maturation factor in astrocytes leads to immune activation
      of microglia through secretion of granulocyte-macrophage-colony stimulating
      factor.
AB  - We infected a mixed culture of primary rat astrocytes and microglia with a
      replication-defective adenovirus carrying the rat glia maturation factor (GMF)
      cDNA. Affymetrix microarray analysis showed a big increase in the expression of
      several major histocompatibility complex (MHC) class II proteins along with
      interleukin-1beta (IL-1beta). Subsequent study using reverse transcription
      polymerase chain reaction (RT-PCR) yielded the same results with the mixed
      culture, but not with pure astrocytes or pure microglia. We also noticed that the
      GMF/virus construct infected only astrocytes but not microglia. This led us to
      suspect that overexpression of GMF in astrocytes resulted in the secretion of an
      active substance that stimulated the microglia to express MHC II and IL-1beta. We
      identified this substance as granulocyte-macrophage-colony stimulating factor (GM
      CSF). MHC II are unique to antigen-presenting cells such as microglia and
      monocytes. The results suggest that GMF in astrocytes can initiate a series of
      events, leading to immune activation in the nervous system, and implicates its
      involvement in autoimmune diseases such as multiple sclerosis.

PMID- 12051701
TI  - A role for mitochondria as potential regulators of cellular life span.
AB  - We demonstrate that by simply raising extracellular pyruvate levels, and hence
      increasing metabolic supply, human diploid fibroblasts undergo a concentration
      dependent induction of cellular senescence. Fibroblasts treated with pyruvate
      undergo a rapid growth arrest accompanied by elevated levels of the cell-cycle
      regulatory molecules p53, p21, and p16. These cells also exhibit a rise in
      mitochondrial oxidant production and a fall in intracellular glutathione levels.
      Exposure of pyruvate treated cells to the antioxidant and glutathione precursor N
      acetylcysteine restores cell growth and reverses the increase in senescence
      associated beta-galactosidase activity. Similarly, we demonstrate that by
      increasing mitochondrial number via retroviral-mediated expression of the
      mitochondrial biogenesis regulator PGC-1 there is also a reduction in cell growth
      and the more rapid induction of senescence. These results suggest that
      mitochondria appear to play a central role in regulating cellular life span.

PMID- 12051702
TI  - Ca(2+) signals in Pmr1-GFP-expressing COS-1 cells with functional endoplasmic
      reticulum.
AB  - We studied the role of the Pmr1-containing Ca(2+) store in COS-1 cells endowed
      with a functional endoplasmic reticulum. Transfected cells could be recognized by
      using a green-fluorescent-protein (GFP)-tagged form of Pmr1. Pmr1-GFP
      fluorescence showed a typical juxtanuclear Golgi-like distribution. Pmr1-GFP
      containing cells with functional endoplasmic reticulum responded to 100 microM
      ATP with baseline Ca(2+) spiking, while non-transfected cells produced an initial
      Ca(2+) peak followed by a long-lasting plateau. The Ca(2+) signal often appeared
      after a long latency in Pmr1-GFP-expressing cells. ATP-stimulated Pmr1-GFP
      expressing cells with functional endoplasmic reticulum responded after a latency
      period to extracellular Ca(2+) with a regenerative Ca(2+) signal, while non
      transfected control cells responded with an immediate slow rise in free cytosolic
      Ca(2+) concentration. These results demonstrate the importance of the Pmr1
      containing Ca(2+) store in generating or modifying cellular Ca(2+) signals.

PMID- 12051703
TI  - Dominant-negative mutant of BIG2, an ARF-guanine nucleotide exchange factor,
      specifically affects membrane trafficking from the trans-Golgi network through
      inhibiting membrane association of AP-1 and GGA coat proteins.
AB  - BIG2 is one of the guanine nucleotide exchange factors (GEFs) for the ADP
      ribosylation factor (ARF) family of small GTPases, which regulate membrane
      association of COPI and AP-1 coat protein complexes and GGA proteins. Brefeldin A
      (BFA), an ARF-GEF inhibitor, causes redistribution of the coat proteins from
      membranes to the cytoplasm and membrane tubulation of the Golgi complex and the
      trans-Golgi network (TGN). We have recently shown that BIG2 overexpression blocks
      BFA-induced redistribution of the AP-1 complex but not TGN membrane tubulation.
      In the present study, we constructed a dominant-negative BIG2 mutant and found
      that when expressed in cells it induced redistribution of AP-1 and GGA1 and
      membrane tubulation of the TGN. By contrast, the mutant did not induce COPI
      redistribution or Golgi membrane tubulation. These observations indicate that
      BIG2 is involved in trafficking from the TGN by regulating membrane association
      of AP-1 and GGA through activating ARF.

PMID- 12051704
TI  - Distribution of dynamins in testis and their possible relation to
      spermatogenesis.
AB  - Dynamin 2 and dynamin 3 are highly expressed in testis. However, their functions
      in the tissue remain unclear. Considering that dynamin 1, neuron-specific isoform
      of dynamin, plays a pivotal role in endocytosis, functions of dynamin 2 and
      dynamin 3 in testis must be essential. Cellular expression and subcellular
      localization of dynamin 2 and dynamin 3 in testis were investigated. Dynamin 2
      and dynamin 3 were highly expressed in germ cells and Sertoli cells, constituents
      of seminiferous tubules. By immunofluorescence it was revealed that dynamin 2
      colocalizes with clathrin both at the plasmamembrane and at Golgi in a cell line
      of Sertoli cells. Immunoreactivity for dynamin 3, on the other hand, appeared as
      finer puncta, which did not colocalize with clathrin, suggesting that these two
      dynamins have distinct functions in Sertoli cells. In the klotho deficient mouse
      testis, which demonstrates disorder in spermatogenesis, expression of dynamin 2
      and dynamin 3 was drastically reduced indicating possible association of these
      proteins with spermatogenesis.

PMID- 12051705
TI  - PQBP-1 increases vulnerability to low potassium stress and represses
      transcription in primary cerebellar neurons.
AB  - PQBP-1 is a polyglutamine tract binding protein implicated in transcription. We
      previously reported that PQBP-1 and mutant ataxin-1, product of the
      spinocerebellar atrophy type 1 (SCA1) causative gene, cooperatively induce cell
      death in culture cells. Simultaneously, we showed that mutant ataxin-1 promoted
      interaction between PQBP-1 and RNA polymerase II and enhanced repression of the
      basal transcription by PQBP-1. In this study, we have examined the effects of
      overexpression of PQBP-1 to the primary-cultured cerebellar neurons. Our results
      indicate that overexpression of PQBP-1 inhibits the basal transcription in
      cerebellar neurons and increases their vulnerability to low potassium conditions.

PMID- 12051706
TI  - Interaction of the C-terminal region of the rat serotonin transporter with
      MacMARCKS modulates 5-HT uptake regulation by protein kinase C.
AB  - The serotonin transporter (SERT) mediates the re-uptake of released serotonin
      into presynaptic nerve terminals. Its activity is regulated by different
      mechanisms including protein kinase C (PKC) triggered internalization. Here, we
      used yeast 2-hybrid screening and cotransfection into 293 cells to identify a
      homologue of the myristoylated alanine-rich C kinase substrate (MARCKS),
      MacMARCKS, as a C-terminally interacting protein of SERT. Upon cotransfection
      with SERT, MacMARCKS caused a reduction in the maximal rate of [(3)H]serotonin
      uptake and reduced its down-regulation elicited by activation of PKC. Our data
      are consistent with MARCKS proteins regulating the plasma membrane dynamics of
      neurotransmitter transporters.

PMID- 12051708
TI  - The nuclear function of angiogenin in endothelial cells is related to rRNA
      production.
AB  - Angiogenin is a potent angiogenic protein whose inhibition is known to prevent
      human tumor growth in athymic mice. It is secreted by both tumor and normal
      cells; and interacts with endothelial and smooth muscle cells to induce a wide
      range of cellular responses including cell migration and invasion, proliferation,
      and formation of tubular structures. Angiogenin is rapidly endocytosed and
      translocated to the cell nucleus where it accumulates in the nucleolus and binds
      to DNA. Although nuclear translocation is necessary for its angiogenic activity,
      the nuclear function of angiogenin is unclear. Here we report that exogenous
      angiogenin enhances the production of 45S rRNA in endothelial cells, and
      reduction of endogenous angiogenin inhibits its transcription. In a nuclear run
      on assay, angiogenin stimulates RNA synthesis including that containing the
      initiation site sequences of 45S rRNA. This suggests that the nuclear function of
      angiogenin relates to its capacity to induce rRNA synthesis. Because rRNA
      transcription is essential for the synthesis of new ribosomes that are necessary
      for protein translation and cell growth, inhibition of angiogenin-stimulated
      transcription of rRNA may inhibit angiogenesis and therefore, would serve as a
      molecular target for therapeutic intervention.

PMID- 12051707
TI  - Follicular dendritic cell of the knock-in mouse provides a new bioassay for human
      prions.
AB  - Infectious prion diseases initiate infection within lymphoid organs where prion
      infectivity accumulates during the early stages of peripheral infection. In a
      mouse-adapted prion infection, an abnormal isoform (PrP(Sc)) of prion protein
      (PrP) accumulates in follicular dendritic cells within lymphoid organs. Human
      prions, however, did not cause an accumulation of PrP(Sc) in the wild type mice.
      Here, we report that knock-in mouse expressing humanized chimeric PrP
      demonstrated PrP(Sc) accumulations in follicular dendritic cells following human
      prion infections, including variant Creutzfeldt-Jakob disease. The accumulated
      PrP(Sc) consisted of recombinant PrP, but not of the inoculated human PrP. These
      accumulations were detectable in the spleens of all mice examined 30 days post
      inoculation. Infectivity of the spleen was also evident. Conversion of humanized
      PrP in the spleen provides a rapid and sensitive bioassay method to uncover the
      infectivity of human prions. This model should facilitate the prevention of
      infectious prion diseases.

PMID- 12051709
TI  - Direct phosphorylation of focal adhesion kinase by c-Src: evidence using a
      modified nucleotide pocket kinase and ATP analog.
AB  - A single mutation in the nucleotide binding pocket of select protein kinases
      allows for use of a bulky, substituted-ATP analog not used by the wild-type
      kinase [1]. Using this approach with the protein tyrosine kinase c-Src, we have
      generated a mutant T338G and expressed it in Src/Yes/Fyn null fibroblasts (SYF1)
      at near endogenous levels. T338G Src exhibits high specificity for a substituted
      ATP analog N(6)-2-phenyl ethyl ATP (peATP), which is not used by wild-type c-Src
      in autophosphorylation nor substrate phosphorylation assays. By employing the
      T338G Src mutant and [gamma-(32)P]peATP analog, we demonstrate that c-Src can
      directly phosphorylate focal adhesion kinase (Fak) in vitro. We also show that
      incubation of permeabilized, T338 Src-expressing cells with peATP causes an
      increase in Fak tyrosine phosphorylation not observed in wild-type Src cells.
      Taken together, these data provide evidence that Src directly phosphorylates Fak
      and demonstrates the limitations of using this modified ATP strategy for analysis
      of direct substrates of protein kinases in permeabilized cells.

PMID- 12051710
TI  - Fasting activates the gene expression of UCP3 independent of genes necessary for
      lipid transport and oxidation in skeletal muscle.
AB  - Fasting triggers a complex array of adaptive metabolic and hormonal responses
      including an augmentation in the capacity for mitochondrial fatty acid (FA)
      oxidation in skeletal muscle. This study hypothesized that this adaptive response
      is mediated by increased mRNA of key genes central to the regulation of fat
      oxidation in human skeletal muscle. Fasting dramatically increased UCP3 gene
      expression, by 5-fold at 15 h and 10-fold at 40 h. However the expression of key
      genes responsible for the uptake, transport, oxidation, and re-esterification of
      FA remained unchanged following 15 and 40 h of fasting. Likewise there was no
      change in the mRNA abundance of transcription factors. This suggests a unique
      role for UCP3 in the regulation of FA homeostasis during fasting as adaptation to
      40 h of fasting does not require alterations in the expression of other genes
      necessary for lipid metabolism.

PMID- 12051711
TI  - Only amyloidogenic intermediates of transthyretin induce apoptosis.
AB  - In diseases like Alzheimer's disease and familial amyloidotic polyneuropathy
      (FAP) amyloid deposits co-localize with areas of neurodegeneration. FAP is
      associated with mutations of the plasma protein transthyretin (TTR). We can here
      show an apoptotic effect of amyloidogenic mutants of TTR on a human neuroblastoma
      cell line. Toxicity could be blocked by catalase indicating a free oxygen radical
      dependent mechanism. The toxic effect was dependent on the state of aggregation
      and unexpectedly mature fibrils from FAP-patients who failed to exert an
      apoptotic response. Morphological studies revealed a correlation between toxicity
      and the presence of immature amyloid. Thus, we can show that toxicity is
      associated with early stages of fibril formation and propose that mature full
      length fibrils represent an inert end stage, which might serve as a rescue
      mechanism.

PMID- 12051712
TI  - The adrenomedullin receptor acts as clearance receptor in pulmonary circulation.
AB  - Adrenomedullin (AM) is a powerful pulmonary vasodilator with antimitogenic
      properties. We investigated the role of the AM receptor (AMR) and the calcitonin
      gene-related peptide type-1 receptor (CGRP1R) in regulating pulmonary vascular AM
      levels. The AMR antagonist hAM(22-52) (120 nmol/L) significantly elevated AM
      release compared with controls to 250% after 2 h in isolated rat lungs and to
      830% after 4 h in pulmonary artery endothelial cells (PAEC). CGRP1R blockade had
      no effect. AMR blockade did not influence prepro-AM mRNA levels nor did
      inhibition of protein synthesis by cycloheximide (0.01 mg/mL) abolish the effect
      of the AMR antagonist. Radioligand-binding studies with PAEC membranes revealed a
      decrease by 44% of the AMR density in response to AMR antagonism. Altogether, the
      pulmonary vascular AMR represents not only a functionally active, but also a
      clearance receptor; its expression is constitutively stimulated by basal AM. This
      identifies a novel mechanism for controlling pulmonary AM levels.

PMID- 12051713
TI  - Regulation of Smad3 expression in bleomycin-induced pulmonary fibrosis: a
      negative feedback loop of TGF-beta signaling.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine involved
      in controlling critical cellular activities including proliferation,
      differentiation, extracellular matrix production, and apoptosis. TGF-beta signals
      are mediated by a family of Smad proteins, of which Smad2 and Smad3 are
      downstream intracellular targets of serine/threonine kinase receptors of TGF
      beta. Although Smad2 and Smad3 are crucial for TGF-beta signaling, little is
      known about the regulation of their expression. In this study, we investigated
      the expression of Smad2 and Smad3 in an in vivo animal model of lung fibrosis
      induced by bleomycin. We found that the expression of Smad3 was regulated in
      lungs during bleomycin-induced pulmonary fibrosis. The decline of Smad3 mRNA was
      evident at day three of post-bleomycin instillation and the expression of Smad3
      continually decreased during the reparative phase of lung injury (days 8 and 12),
      whereas the expression of Smad2 showed little change after bleomycin
      administration. We further investigated whether the expression of Smad3 was
      regulated by TGF-beta in an in vitro lung fibroblast culture system. Our results
      show an immediate translocation of Smad3 protein from the cytoplasm to the
      nucleus and a delayed down-regulation of Smad3 mRNA by TGF-beta in lung
      fibroblasts. These studies provide direct evidence for a differential regulation
      of Smad3 expression that is distinct from that of Smad2 during bleomycin-induced
      pulmonary fibrosis and suggest a ligand-induced negative feedback loop that
      modulates cellular TGF-beta signaling.

PMID- 12051714
TI  - Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site
      Ser45.
AB  - Activation of the canonical Wnt signalling pathway results in stabilisation and
      nuclear translocation of beta-catenin. In the absence of a Wnt signal, beta
      catenin is phosphorylated at four conserved serine and threonine residues at the
      N-terminus of the protein, which results in beta-catenin ubiquitination and
      proteasome-dependent degradation. The phosphorylation of three of these residues,
      Thr41, Ser37, and Ser33, is mediated by glycogen synthase kinase-3 (GSK-3) in a
      sequential manner, beginning from the C-terminal Thr41. It has recently been
      shown that the GSK-3 dependent phosphorylation of beta-catenin requires prior
      priming through phosphorylation of Ser45. However, it is not known whether
      phosphorylation of Ser45 is carried out by GSK-3 itself or by an alternative
      kinase. In this study, the phosphorylation of beta-catenin at Ser45 was
      characterised using a phospho-specific antibody. GSK-3beta was found to be unable
      to phosphorylate beta-catenin at Ser45 in vitro and in intact cells. However,
      inhibition of GSK-3 in intact cells reduced Ser45 phosphorylation, suggesting
      that GSK-3 kinase activity is required for the phosphorylation event. In vitro,
      CK1, but not CK2, phosphorylates Ser45. Ser45 phosphorylation in intact cells is
      not mediated by CK1varepsilon, a known positive regulator of Wnt signalling, as
      overexpression of this kinase leads to decreased phosphorylation levels. In
      conclusion, phosphorylation of beta-catenin at the GSK-3 priming site Ser45 is
      not mediated by GSK-3 itself, but by an alternative kinase, indicating that beta
      catenin is not an unprimed substrate for GSK-3 in vivo. Priming of GSK-3
      dependent phosphorylation of beta-catenin by a different kinase could have
      important implications for the regulation of Wnt signalling.

PMID- 12051715
TI  - Expression of the RNA binding proteins, Mel-N1, Mel-N2, and Mel-N3 in adipose
      cells.
AB  - Mel-N1 (murine embryonic lethal abnormal vision [ELAV]), a mammalian homolog of
      Drosophila ELAV, is an mRNA binding protein of the RNA Recognition Motif family.
      Studies with the human homolog, Hel-N1 have supported the hypothesis that Hel-N1,
      and its splice variant, Hel-N2 play a role in mRNA metabolism. Thus it becomes
      logical to extend this hypothesis to the murine variant Mel-N1 which has been
      described as a neuronal protein with a minor level of expression in the testis.
      Our current work expands the potential function for this protein through
      demonstration of expression of the full-length message and splice variants in
      adipose tissue as well as preadipocyte and adipocyte cell lines.

PMID- 12051716
TI  - Potent inhibition of DNA unwinding and ATPase activities of pea DNA helicase 45
      by DNA-binding agents.
AB  - Pea DNA helicase 45 (PDH45) is an ATP-dependent DNA unwinding enzyme, with
      intrinsic DNA-dependent ATPase activity [Plant J. 24 (2000) 219]. We have
      determined the effect of various DNA-binding agents, such as daunorubicin,
      ethidium bromide, ellipticine, cisplatin, nogalamycin, actinomycin C1, and
      camptothecin on the DNA unwinding and ATPase activities of the plant nuclear DNA
      helicase PDH45. The results show that all the agents except actinomycin C1, and
      camptothecin inhibited the helicase (apparent K(i) values ranging from 1.5 to 7.0
      microM) and ATPase (apparent K(i) values ranging from 2.5 to 11.9 microM)
      activities. This is the first study to show the effect of various DNA-binding
      agents on the plant nuclear helicase and also first to demonstrate inhibition of
      any helicase by cisplatin. Another striking finding that the actinomycin C1 and
      ellipticine act differentially on PDH45 as compared to pea chloroplast helicase
      suggests that the mechanism of DNA unwinding could be different in nucleus and
      chloroplast. These results suggest that the intercalation of the inhibitors into
      duplex DNA generates a complex that impedes translocation of PDH45, resulting in
      both the inhibitions of unwinding activity and ATP hydrolysis. This study would
      be useful to obtain a better understanding of the mechanism of plant nuclear DNA
      helicase unwinding and the mechanism by which these agents can disturb genome
      integrity.

PMID- 12051717
TI  - Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart
      failure.
AB  - Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent
      vasodilators in humans and improved myocardial ischemia is observed after CGRP
      administration. Receptors for CGRP and ADM were already identified in heart.
      Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of
      the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR
      results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR
      gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart
      failure, we investigated whether the CGRP and ADM receptors are upregulated in
      chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot
      analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in
      both atria and ventricles of failing hearts 6 months after aortic banding in
      rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3
      mRNAs and proteins in this model of cardiac failure. No change was observed in
      mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present
      results suggested after congestive heart failure in adult rats, an up-regulation
      of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in
      atria and ventricles and of ADM receptor (by increased RAMP3 expression that is
      associated with CRLR) in atria. These findings support a functional role for CGRP
      and ADM receptors to compensate the chronic heart failure in rats.

PMID- 12051718
TI  - Validation of a quantitative method for real time PCR kinetics.
AB  - Real time RT-PCR is the most sensitive method for quantitation of gene expression
      levels. The accuracy can be dependent on the mathematical model on which the
      quantitative methods are based. The generally accepted mathematical model assumes
      that amplification efficiencies are equal at the exponential phase of the
      reactions for the same amplicon. However, no methods are available to test the
      assumptions regarding amplification efficiency before one starts the real time
      PCR quantitation. Here we further develop and test the validity of a new
      mathematical model which dynamically fits real time PCR data with good
      correlation (R(2)=0.9995+/-0.002, n=50). The method is capable of measuring cycle
      by-cycle PCR amplification efficiencies and demonstrates that these change
      dynamically. Validation of the method revealed the intrinsic relationship between
      the initial amount of gene transcript and kinetic parameters. A new quantitative
      method is proposed which represents a simple but accurate quantitative method.

PMID- 12051720
TI  - Leukemia inhibitory factor relaxes arteries through endothelium-dependent
      mechanism.
AB  - Leukemia inhibitory factor (LIF) is a cytokine, which inhibits angiogenesis and
      decreases endothelial cell proliferation and migration, suggesting that LIF may
      modulate vascular tone. In this study, we examined the effects of LIF on the tone
      of rat arteries. The isometric tension of ring preparations from rat superior
      mesenteric arteries was continuously measured. LIF relaxed the mesenteric
      arteries in a dose-dependent manner, when the arterial rings were precontracted
      with phenylephrine. The relaxation was totally inhibited by mechanical removal of
      endothelium. N(G)-nitro-L-arginine methyl ester did not affect the relaxation by
      LIF. Ca(2+)-dependent K channel (KCa) blockers, apamin with charybdotoxin,
      inhibited the relaxation by LIF. Catalase, an enzyme which scavenges hydrogen
      peroxide, also inhibited the relaxation by LIF. Endothelium-derived
      hyperpolarizing factor relaxes smooth muscle cells and the effect is blocked by
      KCa and catalase. Our results suggest that LIF regulates vascular tone through
      the effect of this factor.

PMID- 12051719
TI  - Age-associated reduction of nuclear protein import in human fibroblasts.
AB  - Age-dependent decreases in the protein concentrations of the nucleocytoplasmic
      transport factors karyopherin alpha2, CAS, and RanBP1 were found by comparing
      fibroblast cultures obtained from young, mature, and old human donors.
      Karyopherin beta1 levels do not change with age and present very little variation
      among donors. The decrease in the concentration of transport factors is
      accompanied by a reduction in the protein import rate in fibroblasts from old
      donors, as detected by a change in the intracellular localization of a test
      transport substrate that shuttles between the cytoplasm and the nucleus.
      Measurements of concentrations of the same import factors in organs and tissues
      of old mice revealed a decrease of CAS in kidney, lung, and spleen. The import
      reduction in old age is expected to lead to impaired activity of proteins whose
      functions depend on timely import into the nuclei.

PMID- 12051721
TI  - Ceramide accumulation is independent of camptothecin-induced apoptosis in
      prostate cancer LNCaP cells.
AB  - We have investigated to determine the source of ceramide produced during the
      genotoxic apoptosis induced by the anti-cancer drug, camptothecin (CPT), in human
      prostate cancer LNCaP cells by measuring the activities of acid and neutral
      sphingomyelinases (SMase) and by using fumonisinB(1) (FB(1)), the inhibitor of
      ceramide synthase involving de novo synthesis of ceramide. In contrast to time
      dependent elevation of intracellular ceramide level after CPT-treatment, the
      activities of both SMases were not increased but rather decreased. Instead,
      pretreatment for 3 h with FB(1) (100 microM), an inhibitor of ceramide synthase,
      almost completely abrogated ceramide accumulation observed in cells exposed to
      CPT for 18 h. These results indicate that ceramide is produced via de novo
      pathway but not via sphingomyelin hydrolysis pathway. Furthermore, it is to be
      noted that the pretreatment with FB(1) did not affect the CPT-induced apoptosis
      as assessed by DNA ladder formation, Hoechst 33342 staining, flow cytometry, and
      mitochondrial potential thereby leading us to propose that ceramide accumulation
      is independent of apoptosis in this system.

PMID- 12051722
TI  - Neurogenic differentiation of murine and human adipose-derived stromal cells.
AB  - The identification of cells capable of neuronal differentiation has great
      potential for cellular therapies. We examined whether murine and human adipose
      derived adult stem (ADAS) cells can be induced to undergo neuronal
      differentiation. We isolated ADAS cells from the adipose tissue of adult BalbC
      mice or from human liposuction tissue and induced neuronal differentiation with
      valproic acid, butylated hydroxyanisole, insulin, and hydrocortisone. As early as
      1-3 h after neuronal induction, the phenotype of ADAS cells changed towards
      neuronal morphology. Following neuronal induction, muADAS cells displayed
      immunocytochemical staining for GFAP, nestin and NeuN and huADAS cells displayed
      staining for intermediate filament M, nestin, and NeuN. Following neuronal
      induction of murine and human ADAS cells, Western blot analysis confirmed GFAP,
      nestin, and NeuN protein expression. Pretreatment with EGF and basic FGF
      augmented the neuronal differentiation of huADAS cells. The neuronal
      differentiation of stromal cells from adipose tissue has broad biological and
      clinical implications.

PMID- 12051723
TI  - Novel oxazolidinone based compounds as inhibitors of aromatase and the use of the
      substrate-heme complex approach in the rationalisation of these compounds.
AB  - The synthesis, biochemical evaluation and molecular modelling of a series of N
      alkylated 4-(4(')-aminobenzyl)-2-oxazolidinones is described involving the
      derivatisation of the starting R- or S-enantiomer of 4-benzyl-2-oxazolidinones.
      The compounds were tested for human placental aromatase (AR) inhibition in vitro
      and were found, in general, to be more potent than the standard compound,
      aminoglutethimide (AG). The inhibitory activity of the compounds was rationalised
      through the use of the novel substrate-heme complex (SHC) approach and suggests
      that the S-enantiomer based compounds protrude beyond the C(13), C(17), and C(16)
      area of the steroid backbone, resulting in steric hindrance with the active site
      of AR and thus reduced inhibitory activity. The R-enantiomer based compounds do
      not protrude in the same area and as such are not thought to undergo any steric
      hindrance and in comparison to the S-enantiomer, possess greater inhibitory
      activity.

PMID- 12051725
TI  - Effects of remote mutation on the autolysis of HIV-1 PR: X-ray and NMR
      investigations.
AB  - Autolysis rates of the C95M and C95M/C1095A mutants of a HIV-1 protease tethered
      dimer have been determined by real time NMR and it is observed that the double
      mutant has approximately two times higher rate. X-ray structure of the
      C95M/C1095A double mutant has been solved and refined to 2.1 A resolution.
      Comparison of the double mutant structure with that of C95M single mutant reveals
      that there is a shift in the position of the catalytic aspartates and the bound
      catalytic water. The mutation also causes a loss of hydrophobic packing near the
      dimerization domain of the protein. These observations demonstrate that subtle
      changes are adequate to cause significant changes in the rate of autolysis of the
      double mutant. This provides a rationale for the effects of remote mutations on
      the activity and drug resistance of the enzyme.

PMID- 12051724
TI  - Estrogen regulation of c-fos gene expression through phosphatidylinositol-3
      kinase-dependent activation of serum response factor in MCF-7 breast cancer
      cells.
AB  - 17Beta-estradiol (E2) induces proliferation and c-fos gene expression in MCF-7
      cells and both responses are partially blocked by wortmannin and LY294002 which
      are inhibitors of phosphatidylinositol-3-kinase (PI3-K). Analysis of the c-fos
      gene promoter shows that the effects of wortmannin and LY294002 are associated
      with inhibition of E2-induced activation through the serum response factor (SRF)
      motif within the proximal serum response element at -325 and -296. E2 activates
      constructs containing multiple copies of the SRF (pSRF) and a GAL4-SRF fusion
      protein; these responses are accompanied by PI3-K-dependent phosphorylation of
      Akt and inhibited by wortmannin/LY294002, the antiestrogen ICI 182780, but not by
      the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD98059. Using a
      series of kinase inhibitors and dominant negative kinase expression plasmids, it
      was shown that the non-genomic activation of SRF by E2 was associated with src
      ras-PI3-K pathway, thus, demonstrating hormonal activation of the SRE through src
      ras activation of both PI3-K- and MAPK-dependent signaling pathways.

PMID- 12051726
TI  - A novel and rapid approach to isolating functional ryanodine receptors.
AB  - Conventional methods of isolating and reconstituting ryanodine receptors (RyRs)
      from native membranes into proteoliposomes take a minimum of 2 days to complete.
      We have developed an alternative strategy that can be used to isolate and
      reconstitute functional RyRs in just 3 h with a similar degree of purification.
      RyRs isolated by this method display characteristic functional behaviour as
      assessed by radioligand binding and single channel analyses.

PMID- 12051727
TI  - Androgen receptor enhances myogenin expression and accelerates differentiation.
AB  - Animal and clinical studies indicated that the androgen-AR signaling pathway is
      required for appropriate development of sexually dimorphic skeletal muscles and
      increases lean muscle mass, muscle strength, and muscle protein synthesis.
      However, the detailed mechanisms by which the androgen-AR signaling pathway
      regulates skeletal muscle development need further study at the molecular level.
      C2C12 myoblast cells stably transfected with the Flag-tagged AR were used to
      analyze the role of androgen-AR signaling pathway in skeletal muscle development.
      The results indicate that the androgen-AR signaling pathway may suppress skeletal
      myoblast cell growth and accelerate myoblast cell differentiation via enhanced
      myogenin expression. This is a first report showing the role of androgen-AR
      signaling pathway in regulation of myoblast cell growth and myogenic regulatory
      factors.

PMID- 12051728
TI  - Involvement of IL-1beta and IL-10 in IFN-alpha-mediated antiviral gene induction
      in human hepatoma cells.
AB  - Crosstalk between interferons (IFNs) and several cytokines is likely to play an
      important role in viral clearance in chronic hepatitides B and C. We investigated
      the influence of this phenomenon on IFN-inducible antiviral gene expression in
      HuH-7 human hepatoma cells. HuH-7 cells were treated with IFN-alpha in the
      absence or presence of interleukin-1beta (IL-1beta) or IL-10 and the expression
      of antiviral genes such as 2(')5(')-oligoadenylate synthetase (2(')5(')-OAS) and
      double-stranded RNA-dependent protein kinase (PKR), as well as activation of
      signal transducer and activator of transcription 1 (STAT1), a key step for
      relaying the IFN-alpha signals, was analyzed by Northern blotting, Western
      blotting, and the reporter gene transfection assay. IL-1beta potentiated IFN
      alpha-induced 2(')5(')-OAS and PKR gene expression, similar to expression of the
      transfected reporter genes containing the IFN-stimulated regulatory elements,
      while IL-10 suppressed IFN-alpha-stimulated gene expression. With regard to IFN
      alpha signaling, IL-1beta enhanced both tyrosine and serine phosphorylation of
      STAT1 through p38 mitogen-activated protein kinase activation. In contrast, IL-10
      inhibited IFN-alpha-mediated tyrosine phosphorylation of STAT1 by induction of a
      Janus kinase inhibitor, JAB. IL-1beta and IL-10 interact with IFN-alpha to up-
      and down-regulate antiviral gene expression, respectively, by modulating STAT1
      activation induced by IFN-alpha.

PMID- 12051729
TI  - Release of a new vascular permeability enhancing peptide from kininogens by human
      neutrophil elastase.
AB  - Stimulated neutrophils produced vascular permeability enhancing (VPE) activity in
      the presence of high molecular weight kininogen (HMWK), which was inhibited
      mainly by a neutrophil elastase (NE) inhibitor or a bradykinin (BK) B(2)-receptor
      antagonist. NE (>3 nM) generated VPE activity from kininogens at normal plasma
      concentrations with the smaller protein being several fold more responsive than
      the larger protein, through releasing a new VPE peptide (E-kinin),
      SLMKRPPGFSPFRSSRI. Synthetic E-kinin, SLMKRPPGFSPFRSS and SLMKRPPGFSPFR had VPE
      and blood pressure lowering activities, which were comparable to the activities
      of BK and completely inhibited by B(2)-receptor antagonists. Interestingly, E
      kinin and SLMKRPPGFSPFRSS did not induce smooth muscle contraction. These results
      suggest that E-kinin formed in vivo may be processed at the carboxy-terminus to
      give a peptide that can bind to the B(2)-receptor. The molecular mechanism for
      neutrophil-associated VPE may be explained by excision of E-kinin from kininogens
      by NE, followed by further processing of the peptide.

PMID- 12051730
TI  - Ultrastructure of nuclear aggregates formed by expressing an expanded
      polyglutamine.
AB  - Intranuclear inclusions have been observed in the brains of patients affected
      with Huntington's disease (HD). Neuro 2A cells that transiently expressed HD exon
      1 bearing 74 glutamine repeats linked to the green fluorescent protein (GFP) and
      the nuclear localization sequence (NLS) contained aggregates in nuclei. The
      aggregates were purified by fractionation with centrifugation followed by
      fluorescence-activated cell sorting (FACS). Heat treatment of the aggregate in an
      SDS sample buffer caused the dense aggregate cores to disappear and generated a
      basket-like structure composed of fibrils. Biochemical analysis of the aggregates
      revealed that the HD exon 1-GFP fusion protein was the major component. The
      heterogeneous nuclear ribonucleoproteins F and H, histones and ubiquitin were
      found to be associated with the aggregates. Our observations suggest that the N
      terminal fragment of huntingtin may organize the skeletal structure of the
      aggregates and may disturb normal cellular functions by trapping other proteins
      within the aggregates.

PMID- 12051731
TI  - Blockade of angiotensin AT1a receptor signaling reduces tumor growth,
      angiogenesis, and metastasis.
AB  - It was reported that angiotensin II stimulates angiogenesis in vivo, and
      angiotensin-converting enzyme (ACE) inhibitors inhibit angiogenesis. We found
      that an AT1-receptor (AT1-R) antagonist, TCV-116, inhibited tumor growth, tumor
      associated angiogenesis, and metastasis in a murine model. Tumor growth of
      Sarcoma 180 (S-180) cells and of fibrosarcoma (NFSA) cells was strongly inhibited
      by administration of TCV-116 in the diet at a dose of approximately 100
      mg/kg/day. This reduction was accompanied with a marked reduction in tumor
      associated angiogenesis. The same treatment also reduced the lung metastasis of
      intravenously injected Lewis lung carcinoma cells. These effects of TCV-116 were
      equivalent to those of the ACE inhibitor, lisinopril. In S-180 and NFSA tumor
      tissues, ACE and AT1a receptor (AT1a-R) mRNAs were expressed when assessed with
      RT-PCR. AT1b receptor and AT2 receptor, however, were not detected.
      Immunoreactive AT1-R was detected mainly on the neovascularized vascular
      endothelial cells in which expression was reduced by TCV-116 and lisinopril.
      These results suggested that TCV-116 inhibits the angiogenesis, growth, and
      metastasis of tumors highly dependent on AT1a-R blockade. Blockade of AT1a-R
      signaling may therefore become an effective novel strategy for tumor
      chemoprevention.

PMID- 12051733
TI  - pc1 and psc1, zebrafish homologs of Drosophila Polycomb and Posterior sex combs,
      encode nuclear proteins capable of complex interactions.
AB  - Drosophila Polycomb group proteins are thought to form multimeric nuclear
      complexes that are responsible for stable transmission of repressed states of
      gene expression during the proliferation of differentiating embryos. In this
      study, we cloned, sequenced, and characterized two Polycomb group homologs,
      designated pc1 and psc1, in zebrafish. Amino acid sequence analyses determined
      that pc1 is a structural homolog of Drosophila Polycomb and that psc1 is a
      homolog of Drosophila Posterior sex combs. Northern blots and whole-mount in situ
      hybridization revealed that pc1 and psc1 had overlapping expression patterns at
      successive stages of embryogenesis. Immunocytochemistry localized both Pc1 and
      Psc1 protein in blastomere nuclei. Pull-down assays and two-hybrid system
      deletion analyses showed that these proteins were capable of homotypic and
      heterotypic interactions and identified the regions required for these
      interactions. The evidence supports the idea that zebrafish Polycomb group
      proteins, like those of other species, form nuclear complexes with compositions
      that may vary in a spatio-temporal manner during development.

PMID- 12051732
TI  - Modulation of alternative pre-mRNA splicing in vivo by pinin.
AB  - Pre-mRNA splicing occurs in a large macromolecular RNA-protein complex called the
      spliceosome. The major components of the spliceosome include snRNP and SR
      proteins. We have previously identified an SR-like protein, pinin (pnn), which is
      localized not only in nuclear speckles but also at desmosomes. The nuclear
      localization of pnn is a dynamic process because pnn can be found not only with
      SR proteins in nuclear speckles but also in enlarged speckles following treatment
      of cells with RNA polymerase II inhibitors, DRB, and alpha-amanitin. Using
      adenovirus E1A and chimeric calcitonin/dhfr construct as a splicing reporter
      minigene in combination with cellular cotransfection, we found that pnn regulates
      alternative 5(') and 3(') splicing by decreasing the use of distal splice sites.
      Regulation of 5(') splice site choice was also observed for RNPS1, a general
      splicing activator that interacts with pnn in nuclear speckles. The regulatory
      ability of pnn in alternative 5(') splicing, however, was not dependent on RNPS1
      and a pnn mutant, lacking the N-terminal 167 amino acids, behaved like a dominant
      negative species, inhibiting E1A splicing when applied in splicing assays. These
      results provide direct evidence that pnn functions as a splicing regulator which
      participates itself directly in splicing reaction or indirectly via other
      components of splicing machinery.

PMID- 12051734
TI  - Transforming growth factor-beta(s) and their receptors in aging rat prostate.
AB  - We hypothesize that rat fetal urogenital sinus mesenchyme (UGM) can induce
      prostatic growth of growth quiescent adult rat prostate through modulations of
      TGFbetas and their receptors. To test this hypothesis, prostatic ducts from aging
      rat prostate (4, 12, 17, 22, and 27 months) were combined with fetal rat UGM and
      grafted under renal capsule of athymic nude mice. At 1, 3, and 5 months the
      tissue recombinants were harvested from renal capsule and analyzed for their
      growth. The gene and protein expression of TGFbeta1, 2, 3 and their receptors,
      TbetaR-I and TbetaR-II, were analyzed by RT-PCR and immunohistochemistry,
      respectively. The results of these experiments demonstrate that prostate ducts
      when combined with rat UGM formed larger grafts as compared to control (prostatic
      ducts without UGM). The older rat prostate recombinants (17, 22, and 27 months)
      formed larger grafts (159 mg/graft) as compared to younger rat prostate (4 and 12
      months) grafts (51 mg/graft). The mRNA and protein expression for TbetaR-I and
      TbetaR-II in 22 and 27 months rat prostate tissue recombinants were significantly
      lower than 4, 12, and 17 month tissue recombinants. However, mRNA expression for
      TGFbeta1, TGFbeta2, and TGFbeta3 did not change with aging rat tissue
      recombinants. The protein expression for TGFbeta1 was significantly up-regulated
      whereas TGFbeta2 and TGFbeta3 were down-regulated with aging prostate tissue
      recombinants. The present study demonstrates for the first time that rat fetal
      UGM differentially induces growth of aging rat prostate in a tissue recombinant
      model. The mechanisms of induction may be through up-regulation of TGFbeta1 and
      down-regulation of TGFbeta2, and TGFbeta3. However, the action of TGFbetas may be
      through TbetaR-I and TbetaR-II independent pathways since these receptors were
      lacking or low in older rat prostate tissue recombinants. These findings are
      important in understanding the mechanisms of UGM mediated prostatic growth.

PMID- 12051735
TI  - Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing
      transgenic mice.
AB  - Gastric intestinal metaplasia occurs as a pathological condition in the gastric
      mucosa. To clarify how an intestine-specific homeobox gene, Cdx2, affects the
      morphogenesis of gastric mucosa, we generated transgenic mice expressing Cdx2 in
      parietal cells. Until Day 18 after birth, the number of parietal cells
      inthegastric mucosa of transgenic mice was the same as for their normal
      littermates. However, at Day 19, we detected several glands in which parietal
      cells disappeared and the proliferating zone moved from the isthmus to the base
      of the glands. Thereafter, parietal cells decreased gradually and disappeared at
      Day 37. All of the gastric mucosal cells, except for enterochromaffin-like (ECL)
      cells, were completely replaced by intestinal metaplasia, consisting of goblet
      cells, enteroendocrine cells, and absorptive cells expressing alkaline
      phosphatase. Pseudopyloric gland metaplasia was also formed. The transgenic mouse
      is a very useful model for clarifying physiological differentiation of gastric
      and intestinal cell lineages and analyzing the molecular events from intestinal
      metaplasia to adenocarcinoma.

PMID- 12051736
TI  - Enhanced expression of insulin-like growth factor binding protein-3 sensitizes
      the growth inhibitory effect of anticancer drugs in gastric cancer cells.
AB  - Insulin-like growth factor (IGF)-I and -II are potent mitogens and their
      mitogenic effects are modulated by IGF binding proteins (IGFBPs). In this study,
      we evaluated whether the enhanced expression of IGFBP-3 may increase the
      sensitivity of human gastric cancer cells to the anticancer drugs. We further
      investigated the potential mechanism for the growth inhibitory effect of
      anticancer drug induced-IGFBP-3 expression. These IGFBP-3-expressing gastric
      cancer cells showed a lower proliferation rate than IGFBP-3-non-expressing cells.
      Treatment with anticancer drugs resulted in up-regulation of IGFBP-3 expression
      in IGFBP-3-expressing cells. Interestingly the anticancer drug-induced-growth
      inhibition was more evident in IGFBP-3-expressing cells causing the IGFBP-3
      expressing cells but not the IGFBP-3 non-expressing cells to accumulate in the
      G1/G0 phase and induce apoptosis. The exogenous addition of IGFBP-3 inhibited the
      growth of IGFBP-3-non-expressing cells, causing them to undergo apoptosis. Our
      data suggest that IGFBP-3 may have an important role in the biology of gastric
      cancer cell growth and provides a potential marker for predicting the
      responsiveness to anticancer drugs.

PMID- 12051737
TI  - Functional interaction between Brn-3a and Src-1 co-activates Brn-3a-mediated
      transactivation.
AB  - The Brn-3a POU domain transcription factor is able to regulate the transcription
      of promoters containing a Brn-3 response element via its POU domain. In addition,
      the POU domain of Brn-3a has been shown to functionally interact with the
      estrogen receptor and regulate transcription from estrogen responsive promoters.
      The steroid receptor coactivator, Src-1, enhances transcription with a variety of
      steroid receptors. Here we describe a functional interaction between Brn-3a and
      Src-1. In glutathione S-transferase pull-down assays Src-1 was shown to
      specifically interact with Brn-3 proteins. Moreover, Src-1 co-immunoprecipitated
      from intact cells with Brn-3a. The transactivation potential of the Brn-3a/Src-1
      complex was tested on both the Brn-3 responsive SNAP-25 promoter and the estrogen
      responsive vitellogenin promoter, in each of two different cell lines, the
      neuronal ND7 cell line, and the kidney BHK21 cell line. Src-1 consistently and
      strongly potentiated the activation of Brn-3a on the SNAP promoter construct in
      both the ND7 and BHK21 cell lines. The vitellogenin promoter construct, however,
      was only weakly activated by the Brn-3/Src-1 complex in the ND7 cells and there
      was even less effect on this promoter in the BHK21 cells. These results suggest a
      functional role for Src-1 in enhancing Brn-3a mediated transactivation, seemingly
      independent of nuclear hormone receptors, thus broadening the transcriptional
      repertoire of both Brn-3a and Src-1.

PMID- 12051738
TI  - The N-terminal splice product NF1-10a-2 of the NF1 gene codes for a transmembrane
      segment.
AB  - One important function of the neurofibromatosis type 1 (NF1) product
      neurofibromin is the negative regulation of Ras activity on the cell membrane.
      Here, we describe an alternative splice product of the N-terminus of the NF1
      gene. In this splice product, termed NF1-10a-2, the 45 bp exon 10a-2 is inserted
      between exons 10a and 10b. Amino acid sequence analysis for motifs showed that
      the new splice product contains a transmembrane segment not found in wild-type
      neurofibromin. The overall expression was found to be very low in comparison to
      the expression of the wild-type mRNA in all human primary and tumor cells
      examined. Because transcripts were found in the majority of human tissues
      examined, we assume a housekeeping function of this splice product. Investigation
      of the intracellular localization of an NF1-10a-2-EGFP fusion protein in HeLa
      cells revealed a preferential localization in perinuclear granular structures. We
      therefore assume that NF1-10a-2 has a function on an intracellular membrane.

PMID- 12051739
TI  - PP1 phosphatase is involved in Bcl-2 dephosphorylation after prolonged mitotic
      arrest induced by paclitaxel.
AB  - During mitotic arrest induced by paclitaxel, most of the mitochondrial Bcl-2 is
      phosphorylated. This mitotic arrest is transient; exit from mitosis, due to
      mitotic slippage, occurs and Bcl-2 is rapidly dephosphorylated. In the present
      study, we characterized PP1 as the cytosolic phosphatase involved in Bcl-2
      dephosphorylation. When mitochondria and cytosol prepared from mitotic arrested
      cells were incubated in vitro, the proportion of phosphorylated forms of Bcl-2 in
      mitochondria remained unchanged. In contrast, cytosol prepared from cells during
      mitotic slippage led to a dose-dependent loss of phosphorylated forms of Bcl-2.
      Depletion of these cytosol extracts by microcystin-Sepharose maintained Bcl-2
      phosphorylated forms, indicating that this cytosol possessed phosphatase
      activity. Furthermore, the dephosphorylation of Bcl-2 by cytosol prepared from
      cells exiting mitotic block was inhibited by okadaic acid, at a dose known to
      inhibit PP1, and by inhibitor 2, a specific inhibitor of PP1 and by
      immunodepletion of PP1. Finally, we showed that PP1 is associated with
      mitochondrial Bcl-2 in vivo. Taken together, these results demonstrate that PP1
      is directly involved in Bcl-2 dephosphorylation during mitotic slippage.

PMID- 12051740
TI  - Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus
      type 1.
AB  - Replication of human immunodeficiency virus type 1 (HIV-1) is regulated at
      reverse transcription. Cellular topoisomerase I has been reported to be carried
      into HIV-1 virions and enhance cDNA synthesis in vitro, suggesting that
      topoisomerase I expressed in virus producer cells regulates reverse
      transcription. Here, by employing both indicator cell assay and endogenous
      reverse transcription (ERT) assay, we show that topoisomerase I and adenosine
      triphosphate (ATP) enhanced cDNA synthesis of HIV-1. In addition, topoisomerase I
      mutants, R488A and K532A, lacking enzymatic activity, attenuated the efficiency
      of cDNA synthesis and resulted in inhibition of the infectivity of HIV-1,
      suggesting that the activity of topoisomerase I lacking in these mutants is
      indispensable for the cDNA synthesis in the HIV-1 replication process.
      Furthermore, ATP could dissociate topoisomerase I from the topoisomerase I-RNA
      complex and enhance cDNA synthesis in vitro. These findings suggest that cellular
      topoisomerase I and ATP play a pivotal role in the synthesis of cDNA of HIV-1.

PMID- 12051741
TI  - Mammalian DSCAMs: roles in the development of the spinal cord, cortex, and
      cerebellum?
AB  - Central nervous system (CNS) development involves neural patterning, neuronal and
      axonal migrations, and synapse formation. DSCAM, a chromosome 21 axon guidance
      molecule, is expressed by CNS neurons during development and throughout adult
      life. We now report that DSCAM and its chromosome 11 paralog DSCAML1 exhibit
      inverse ventral-dorsal expression patterns in the developing spinal cord and
      distinct, partly inverse, expression patterns in the developing cortex, beginning
      in the Cajal-Retzius cells. In the adult cortex, DSCAM predominates in layer 3/5
      pyramidal cells and DSCAML1 predominates in layer 2 granule cells. In the
      cerebellum, DSCAM is stronger in the Purkinje cells and DSCAML1 in the granule
      cells. Finally, we find that the predicted DSCAML1 protein contains 60 additional
      N-terminal amino acids which may contribute to its distinct expression pattern
      and putative function. We propose that the DSCAMs comprise novel elements of the
      pathways mediating dorsal-ventral patterning and cell-fate specification in the
      developing CNS.

PMID- 12051742
TI  - AMP-activated protein kinase kinase: detection with recombinant AMPK alpha1
      subunit.
AB  - The AMP-activated protein kinase (AMPK) is a heterotrimeric serine/threonine
      protein kinase important for the responses to metabolic stress. It consists of a
      catalytic alpha subunit and two non-catalytic subunits, beta and gamma, and is
      regulated both by the allosteric action of AMP and by phosphorylation of the
      alpha and beta subunits catalyzed by AMPKK(s) and autophosphorylation. The Thr172
      site on the alpha subunit has been previously characterized as an activating
      phosphorylation site. Using bacterially expressed AMPK alpha1 subunit proteins,
      we have explored the role of Thr172-directed AMPKKs in alpha subunit regulation.
      Recombinant alpha1 subunit proteins, representing the N-terminus, have been
      expressed as maltose binding protein (MBP) 6x His fusion proteins and purified to
      homogeneity by Ni(2+) chromatography. Both wild-type alpha1(1-312) and alpha1(1
      312)T172D are inactive when expressed in bacteria, but the former can be fully
      phosphorylated (1 mol/mol) on Thr172 and activated by a surrogate AMPKK,
      CaMKKbeta. The corresponding AMPKalpha1(1-392), an alpha construct containing its
      autoinhibitory sequence, can be similarly phosphorylated, but it remains
      inactive. In an insulinoma cell line, either low glucose or 5-aminoimidazole-4
      carboxamide ribonucleoside (AICAR) treatment leads to activation and T172
      phosphorylation of endogenous AMPK. Under the same conditions of cell incubation,
      we have identified an AMPKK activity that both phosphorylates and activates the
      recombinant alpha1(1-312), but this Thr172-directed AMPKK activity is unaltered
      by low glucose or AICAR, indicating that it is constitutively active.

PMID- 12051743
TI  - Synaptotagmin-like protein 5: a novel Rab27A effector with C-terminal tandem C2
      domains.
AB  - Synaptotagmin-like proteins 1-4 (Slp1-4) are new members of the carboxyl-terminal
      type (C-type) tandem C2 proteins and are classified as a subfamily distinct from
      the synaptotagmin and the Doc2 families, because the Slp family contains a unique
      homology domain at the amino terminus, referred to as the Slp homology domain
      (SHD). We previously showed that the SHD functions as a binding site for Rab27A,
      which is associated with human hemophagocytic syndrome (Griscelli syndrome) [J.
      Biol. Chem. 277 (2002) 9212; J. Biol. Chem. 277 (2002) 12432]. In the present
      study, we identified a novel member of the Slp family, Slp5. The same as other
      Slp family members, the SHD of Slp5 preferentially interacted with the GTP-bound
      form of Rab27A and marginally with Rab3A and Rab6A, both in vitro and in intact
      cells, but not with other Rabs tested (Rab1, Rab2, Rab4A, Rab5A, Rab7, Rab8,
      Rab9, Rab10, Rab11A, Rab17, Rab18, Rab20, Rab22, Rab23, Rab25, Rab28, and Rab37).
      However, unlike other members of the Slp family, expression of Slp5 mRNA was
      highly restricted to human placenta and liver. Expression of Slp5 protein and in
      vivo association of Slp5 with Rab27A in the mouse liver were further confirmed by
      immunoprecipitation. The results suggest that Slp5 might be involved in Rab27A
      dependent membrane trafficking in specific tissues.

PMID- 12051745
TI  - Induction of human aquaporin-1 gene by retinoic acid in human erythroleukemia HEL
      cells.
AB  - Retinoids have been implicated in the control of cell proliferation,
      differentiation, and developmental processes. We report here that aquaporin-1
      (AQP1) is specifically induced by retinoic acid (RA) in human erythroleukemia HEL
      cells. Both all-trans-RA (ATRA) and 9-cis-RA (9CRA) strongly induced the AQP1
      mRNA and protein in a dose-dependent manner. AQP1 protein was mainly expressed in
      plasma membrane in cells induced by RAs. To identify the RA response element
      (RARE) in the human AQP1 promoter, the 5(')-flanking region of AQP1 promoter was
      isolated and transient transfection experiment in HEL cells was performed.
      Deletion analysis of the AQP1 promoter revealed that one putative DR5-like RARE
      with five spaces was located in the region from -2218 to -2202;
      AGGGCAgggacAGGTGA. Electrophoretic mobility shift assay (EMSA) experiment
      demonstrated that two slowly migrated complexes (C1 and C2) capable of binding
      the RARE sequence were present in nuclear extracts prepared from cells and the
      complex C1 was strongly increased in nuclear extracts by RA stimulation. The
      complexes C1 and C2 were significantly abolished by an excess unlabeled probe.
      These results indicate that RAs strongly stimulate the human AQP1 gene expression
      through the RARE and define a novel role in the regulation of erythropoiesis.

PMID- 12051744
TI  - Glucocorticoids regulate the CCSP and CYP2B1 promoters via C/EBPbeta and delta in
      lung cells.
AB  - Glucocorticoids have several important roles in the lung and play a key role in
      lung development and maturation. However, the specific molecular mechanisms of
      glucocorticoid action in lung are unclear. In this study, we have investigated
      two glucocorticoid-regulated genes expressed in the lung epithelium, the
      secretory protein CCSP, and the P450-enzyme CYP2B1. In transient transfections of
      lung epithelial cells, glucocorticoids increased expression from the CCSP and
      CYP2B1 promoters and we demonstrated that induction was dependent on the
      integrity of C/EBP-binding sites in both promoters. Electrophoretic mobility
      shift assays revealed increased DNA-binding of C/EBPbeta and C/EBPdelta after
      glucocorticoid treatment, which was not correlated to altered protein levels. The
      results of this study indicate a previously unknown role for C/EBP transcription
      factors in glucocorticoid signaling in the lung epithelium.

PMID- 12051747
TI  - Structural characterization of a 2'F-RNA aptamer that binds a HIV-1 SU
      glycoprotein, gp120.
AB  - Here we describe the isolation of specific 2'F-substituted RNA ligands for the SU
      glycoprotein, gp120, of HIV-1 strain HXB2. These aptamers bind the target protein
      with an affinity of the order of 10(-7) M. Binding was specific to SU
      glycoprotein and directed to a non-neutralizing epitope that was not shared with
      the related strain, HIV-1(BaL). The structure of one aptamer was defined by a
      combination of deletion analysis and enzymatic probing studies, revealing a 42 nt
      minimal element comprising a three-helix junction that retained the binding
      affinity of the parental sequence. Interestingly, binding to SU glycoprotein was
      accompanied by structural changes in the aptamer that stabilized the weakest of
      the 3 helices.

PMID- 12051746
TI  - pH-sensitive liposomes are efficient carriers for endoplasmic reticulum-targeted
      drugs in mouse melanoma cells.
AB  - Tyrosinase, the key enzyme of melanin biosynthesis, is inactivated in melanoma
      cells following the incubation with the imino-sugar N-butyldeoxynojirimycin, an
      inhibitor of the endoplasmic reticulum N-glycosylation processing. We have
      previously shown that tyrosinase inhibition requires high NB-DNJ concentrations,
      suggesting an inefficient cellular uptake of the drug. Here we show that the use
      of pH-sensitive liposomes composed of dioleoylphosphatidylethanolamine and
      cholesteryl hemisuccinate for the delivery of NB-DNJ reduced the required dose
      for tyrosinase inhibition by a factor of 1000. The results indicate that these pH
      sensitive liposomes are efficient carriers for imino-sugars delivery in the
      endoplasmic reticulum of mammalian cells.

PMID- 12051748
TI  - Matrix protein gene expression in intervertebral disc cells subjected to altered
      osmolarity.
AB  - Physiologic loading of the intervertebral disc may lead to changes in the osmotic
      pressure experienced by the resident cells. In this study, changes in gene
      expression levels for extracellular matrix and cytoskeletal proteins were
      quantified in disc cells subjected to hypo-osmotic (255 mOsm) or hyper-osmotic
      conditions (450 mOsm), relative to iso-osmotic conditions (293 mOsm). Important
      differences were observed in osmolarity and between cells of different regions,
      corresponding to the transition zone and nucleus pulposus. Under hypo-osmotic
      conditions, gene expressions for aggrecan and type II collagen were up-regulated
      in the transition zone, but not in the nucleus pulposus cells. Genes for the
      small proteoglycans, biglycan, and decorin, but not lumican, were up-regulated in
      transition zone cells following incubation in either hypo- or hyper-osmotic
      media. The same genes were down-regulated in nucleus pulposus cells under either
      hypo- or hyper-osmotic conditions. Differences in the response to altered
      osmolarity between cells of the intervertebral disc may relate to their different
      cytoskeletal structures or embryological origins.

PMID- 12051750
TI  - APC0576, a novel inhibitor of NF-kappaB-dependent gene activation, prevents pro
      inflammatory cytokine-induced chemokine production in human endothelial cells.
AB  - Endothelial cells participate in the inflammatory and immune reactions.
      Endothelial cell activation is a recurrent phenomenon linked to the pathogenesis
      of diverse human diseases, such as acute and chronic inflammation and
      cardiovascular disorders. Pro-inflammatory cytokines (e.g., IL-1, TNF) are well
      known activators of endothelial cells, since they strongly induce production of
      chemokines (e.g., IL-8, MCP-1) and cell adhesion molecules, resulting in an
      activation of inflammatory transcription factors such as NF-kappaB. We have
      established a cell-based reporter assay for the NF-kappaB-dependent gene
      activation in HUVEC. Using this assay system, we have identified a novel
      synthetic small molecule, APC0576, 5-(((S)-2,2
      dimethylcyclopropanecarbonyl)amino)-2-(4-(((S)-2,2
      dimethylcyclopropanecarbonyl)amino)phenoxy)pyridine, as an inhibitor of IL-1
      induced NF-kappaB-dependent gene activation without any adverse effects on the
      cell viability. APC0576 represses the IL-1-induced release of chemokines (e.g.,
      IL-8, MCP-1) in HUVEC. This inhibitory effect occurred at the level of mRNA
      expression. Despite having a strong inhibitory effect on the NF-kappaB-dependent
      transcriptional activation, APC0576 does not inhibit the IL-1-induced DNA binding
      of NF-kappaB, degradation of I-kappaB-alpha, or phosphorylation of RelA (p65).
      Although its molecular mechanism of action is not yet clear, APC0576 is a
      promising therapeutic candidate for diverse diseases involved in the pathogenic
      endothelial activation.

PMID- 12051749
TI  - CXCL8((3-73))K11R/G31P antagonizes ligand binding to the neutrophil CXCR1 and
      CXCR2 receptors and cellular responses to CXCL8/IL-8.
AB  - We recently reported that CXCL8((3-73))K11R is a high affinity agonist of
      neutrophil activation and chemotactic responses. In this report we employed
      CXCL8((3-73))K11R as a template to generate CXCL8/IL-8 analogues with antagonist
      activities, using site-directed mutagenesis to introduce conservative amino acid
      substitutions into the first turn within the molecule's beta-pleated sheet region
      (G31P, P32G) and, in association with these, into the putative receptor
      recognition site (T12S, H13F, F17S). We then examined their impact on the
      analogues' biological activities and found that a G31P substitution rendered
      CXCL8((3-73))K11R a high affinity antagonist of CXCL8/IL-8. The ranking (in the
      order of decreasing CXCL8/IL-8 antagonist activities) of the CXCL8((3-73))K11R
      analogues we generated was, G31P>T12S/G31P>H13F/G31P>T12S/H13F/G31P>>P32G
      approximately T12S/P32G approximately H13F/P32G>T12S/H13F/P32G; CXCL8((3
      73))K11R/F17S did not inhibit CXCL8/IL-8-dependent responses. CXCL8((3
      73))K11R/G31P had no discernible agonist (beta-glucuronidase release,
      chemotactic) activity, but at 12.5 ng/ml it bound to purified neutrophils more
      avidly than did 1.25 microg/ml CXCL8/IL-8. Furthermore, CXCL8((3-73))K11R/G31P
      competitively antagonized the binding of CXCR1- and CXCR2-specific antibodies to
      these receptors. Taken together, these data thus provide further impetus to the
      study of the potential efficacy of CXCL8((3-73))K11R/G31P as a broad-spectrum
      antagonist of the ELR-CXC chemokines in experimental and clinical settings.

PMID- 12051751
TI  - Flp recombinase transgenic mice of C57BL/6 strain for conditional gene targeting.
AB  - We constructed an expression vector of Flp recombinase modified by adding a
      nuclear localization signal. Injection of the expression vector into fertilized
      eggs of the C57BL/6 strain yielded transgenic mouse lines expressing the Flp
      recombinase transgene in the testis. We crossed the transgenic mice to reporter
      mice carrying the neomycin phosphotransferase gene flanked by target sites of Flp
      recombinase. Examination of the deletion of the neomycin phosphotransferase gene
      in the progeny showed that Flp-mediated recombination took place efficiently in
      vivo in FLP66 transgenic mouse line. These results suggest that the Flp
      recombinase system is effective in mice and in combination with the Cre
      recombinase system extends the potentials of gene manipulation in mice. One of
      the useful applications of FLP66 transgenic mouse line is the removal of marker
      genes from mice manipulated for the conditional gene targeting with the Cre/loxP
      system in the pure C57BL/6 genetic background.

PMID- 12051752
TI  - Preparation of well-defined bovine polyhemoglobin based on dimethyl adipimidate
      and glutaraldebyde cross-linkage.
AB  - A well-defined bovine polyhemoglobin was prepared by dimethyl adipimidate (DMA)
      and glutaraldehyde double cross-linkage method. DMA was used to block some amino
      groups of hemoglobin, followed by further polymerization with glutaraldehyde. The
      amino modification degree of hemoglobin was 32% when DMA reacted with hemoglobin
      at the molar ratio of 200. The bovine polyhemoglobin with narrow molecular weight
      distribution (mainly 128 kDa) was obtained when glutaraldehyde reacted with DMA
      modified hemoglobin. The P(50) and the Hill coefficient for DMA-modified
      hemoglobin were 19.4 mm Hg and 2.28, respectively, while those for the bovine
      polyhemoglobin were 15.1 mm Hg and 1.70, respectively. The number of Bohr protons
      released for DMA-modified hemoglobin and the polyhemoglobin was 0.86 and 0.56
      H/tetramer, respectively.

PMID- 12051753
TI  - Enhanced expression of GTP cyclohydrolase I in V-1-overexpressing PC12D cells.
AB  - Three of the catecholamine-synthesizing enzymes, i.e., tyrosine hydroxylase (TH),
      aromatic l-amino acid decarboxylase, and dopamine beta-hydroxylase, were earlier
      shown to be up-regulated in cloned PC12D cells overexpressing V-1, a cdc10/SWI6
      motif-containing protein. GTP cyclohydrolase I (GCH) is the rate-limiting enzyme
      for the biosynthesis of tetrahydrobiopterin (BH(4)), known as an essential
      cofactor for TH; and here we found the increased expression of GCH in V-1
      overexpressing clones. Both GCH activity and total biopterin content were highly
      increased in the V-1 clones; whereas the activity of sepiapterin reductase,
      enzyme in the final step of the BH(4) biosynthesis, was not altered. Biochemical
      analyses revealed increased levels of GCH protein, mRNA, and transcription in the
      V-1 clones. Promoter analysis showed increased reporter activity in the construct
      with 150 bp of the promoter region of the human GCH gene, suggesting the
      involvement of cAMP-responsive element-mediated transcriptional regulation.

PMID- 12051754
TI  - CYP2D6.10 present in human liver microsomes shows low catalytic activity and
      thermal stability.
AB  - Comparing bufuralol 1'-hydroxylase activity among liver microsomes prepared from
      individuals whose CYP2D6 genotypes had been determined, we found that the
      activity tended to decrease depending on the number of the CYP2D6*10 allele. Pre
      incubation of liver microsomes from individuals homozygous for the CYP2D6*10
      allele resulted in a decrease in the enzyme activity more rapidly than those from
      individuals homozygous for the CYP2D6*1, suggesting that not only the catalytic
      activity but also the thermal stability of the enzyme appeared to be affected by
      the genetic polymorphism. To confirm this hypothesis, the kinetic parameters of
      CYP2D6.1 and CYP2D6.10 were compared for bufuralol 1'-hydroxylation and
      dextromethorphan O-demethylation using microsomes prepared from yeast transformed
      with plasmids carrying CYP2D6 cDNAs (*1A and *10B). Kinetic studies of these
      CYP2D6 forms indicated clear differences in the metabolic activities between the
      wild (CYP2D6.1) and the mutant enzymes (CYP2D6.10). Bufuralol 1(')-hydroxylase
      activity in microsomes of yeast expressing CYP2D6.10 was rapidly decreased by
      heat treatment, supporting the idea that the thermal stability of the enzyme was
      reduced by amino acid replacement from Pro (CYP2D6.1) to Ser (CYP2D6.10). These
      data strongly suggest that the thermal instability together with the reduced
      intrinsic clearance of CYP2D6.10 is one of the causes responsible for the known
      fact that Orientals show lower metabolic activities than Caucasians for drugs
      metabolized mainly by CYP2D6, because of a high frequency of CYP2D6*10 in
      Orientals.

PMID- 12051755
TI  - Arachidonic acid increases intracellular calcium in erythrocytes.
AB  - Recently, we have measured in erythrocytes a voltage-modulated and
      dihydropyridine-inhibited calcium influx. Since arachidonic acid and other
      polyunsaturated fatty acids influence the activities of most ion channels, we
      studied their effects on the erythrocyte Ca(2+) influx. It was measured on fresh
      erythrocytes, isolated from healthy donors, using the fluorescent dye Fura 2 as
      indicator of [Ca(2+)](i). AA (5-50 microM) and EPA (20-30 microM) stimulated a
      concentration-dependent increase in [Ca(2+)](i), deriving from extracellular
      calcium (1 mM), without affecting the intra- and extracellular pH and membrane
      voltage. The Ca(2+) influx rate varied from 0.5 to 3 nM Ca(2+)/s in the presence
      of AA and from 0.9 to 1.7 nM Ca(2+)/s with EPA. The Ca(2+) influx elicited by AA
      and EPA was not inhibited by dihydropyridines, while cyclooxygenase inhibitors
      were effective and PGE1 or PGE2 did not produce any effect. We conclude that AA
      could activate an erythrocyte voltage-independent Ca(2+) transport via an
      intermediate product of cyclooxygenase pathway; however, a direct interaction
      with the membrane lipid-protein cannot be excluded.

PMID- 12051756
TI  - Metabolic responses induced by thrombin in human umbilical vein endothelial
      cells.
AB  - Metabolic responses induced by thrombin in human umbilical vein endothelial cells
      (HUVECs) were investigated by using the cytosensor technique. Thrombin increased
      the extracellular acidification rate of endothelial cells, measured as an index
      of metabolic activity with a cytosensor microphysiometer, in a concentration
      dependent fashion with an EC(50) of 1.27+/-0.59 IU/ml, which was abolished by the
      MAP kinase inhibitor PD98059. When intracellular Ca(2+) was chelated or PKC was
      inactivated, PD98059 failed to abolish the thrombin-induced acidification rate
      response in HUVECs. In addition, the tyrosine kinase inhibitor genistein, PKC
      inhibitor calphostin C, and Na(+)/H(+)exchanger antagonist MIA also partly
      inhibited thrombin-induced acidification rate responses. It is suggested that
      thrombin stimulated rapid metabolic responses via MAP kinase in HUVECs, which are
      calcium- and PKC-dependent.

PMID- 12051758
TI  - Subgenomic replicon derived from a cell line infected with the hepatitis C virus.
AB  - Recently, cell culture systems have been established, where a hepatitis C virus
      (HCV) subgenomic replicon was efficiently replicated and maintained for a long
      period. To see whether a HCV sequence derived from HCV-infected cultured cell
      sequence can be used for the construction of a functional replicon, a HCV
      subgenomic RNA carrying a neomycin-resistant gene was constructed using the HCV
      genome RNA obtained from cultured cells infected with HCV. After transfection,
      G418-resistant Huh-7 cells were selected and subcloned. Finally, the production
      of HCV proteins and de novo synthesis of subgenomic RNA were confirmed in the
      selected cell clone, indicating that this subgenomic RNA replicated in cultured
      cells and functioned as a replicon. These results suggest that the HCV genome
      obtained from an in vitro HCV infection system with cultured cells can be used to
      develop a subgenomic replicon system with diverse HCV sequences.

PMID- 12051757
TI  - Ubiquitin-like proteins and Rpn10 play cooperative roles in ubiquitin-dependent
      proteolysis.
AB  - Rpn10, a subunit of the 26S proteasome, has been proposed to act as a receptor
      for multiubiquitin chains in ubiquitin-dependent proteolysis. However, studies on
      RPN10-deleted mutants in yeasts have suggested the presence of other
      multiubiquitin chain-binding factors functioning in ubiquitin-dependent
      proteolysis. Here, we report that a mutant with a triple deletion of RAD23, DSK2,
      and RPN10 genes accumulates large amounts of polyubiquitinated proteins, as is
      the case with a mutant with RAD23 and DSK2 deletions under restrictive
      conditions. Dsk2, Rad23, and Rpn10 have different capacities to bind
      multiubiquitin chains. Another ubiquitin-like protein, Ddi1, has similar activity
      to those of Rad23 and Dsk2. Taken together, the results suggest that ubiquitin
      like proteins, Rad23, Dsk2, possibly Ddi1, and Rpn10 play cooperative roles in
      ubiquitin-dependent proteolysis, serving as multiubiquitin chain-binding
      proteins.

PMID- 12051759
TI  - ERK1/2 mediates PDGF-BB stimulated vascular smooth muscle cell proliferation and
      migration on laminin-5.
AB  - During restenosis following arterial injury, vascular smooth muscle cells (VSMCs)
      form a neointimal layer in arteries by changing from a differentiated,
      contractile phenotype to a dedifferentiated, migratory, and proliferative
      phenotype. Several growth factors, cytokines, and extracellular matrix components
      released following injury have been implicated in these phenotypic changes. We
      have recently detected the expression of laminin-5, an ECM protein found
      predominantly in epithelial tissues, in the arterial vasculature. Here we report
      that ln-5 expression by VSMC is upregulated by platelet-derived growth factor
      (PDGF-BB), epidermal growth factor, basic fibroblast growth factor, and
      transforming growth factor-beta1. Adhesion to ln-5 specifically enhances PDGF-BB
      stimulated VSMC proliferation and migration. PD98059, a specific inhibitor of the
      ERK1/2 members of the Mitogen Activated Protein kinase family, increases both
      VSMC adhesion to ln-5 and blocks PDGF-BB-stimulated VSMC migration on ln-5. These
      results suggest that adhesion to ln-5 mediates a PDGF-BB-stimulated VSMC response
      to vascular injury via an ERK1/2 signaling pathway.

PMID- 12051760
TI  - Remnant lipoprotein particles are taken up into myocardium through VLDL receptor-
      a possible mechanism for cardiac fatty acid metabolism.
AB  - The VLDL (very low-density lipoprotein) receptor is a peripheral lipoprotein
      receptor expressing in fatty acid active tissues abundantly. In the Balb/c
      fasting mice, VLDL receptor as well as LPL (lipoprotein lipase), FAT (fatty acid
      translocase)/CD36, H-FABP (heart-type fatty acid-binding protein), ACS (acyl-CoA
      synthetase) and LCAD (long-chain acyl-CoA dehydrogenase) expressions increased.
      An electron microscopic examination indicated the lipid droplets that accumulated
      in the hearts of fasting Balb/c mice. During the development of SD (Sprague
      Dawley) rats, VLDL receptor, LPL, FAT/CD36, H-FABP, ACS, and LCAD mRNAs
      concomitantly increased with growth. However, PK (pyruvate kinase) mRNA
      expression was negligible. In cultured neonatal rat cardiomyocytes, VLDL receptor
      expression increased with days in culture. Oil red-O staining showed that
      cardiomyocytes after 7 days in culture (when the VLDL receptor protein is
      present) accumulated beta-migrating VLDL. Thereby, we showed that the cardiac
      VLDL receptor pathway for delivery of remnant lipoprotein particles might be part
      of a cardiac fatty acid metabolism.

PMID- 12051761
TI  - NMR evidence for different conformations of the bioactive region of rat CCK-8 and
      CCK-58.
AB  - Sulfated CCK-58 and CCK-8 have identical bioactive C-terminal primary sequences
      but distinct C-terminal solution structures and different bioactivities. To
      examine structural differences in greater detail, rat CCK-58 and -8 were
      synthesized with isotopic enrichment of C-terminal residues with (15)N at alpha
      amino nitrogens. Proton and nitrogen chemical shift assignments of peptide
      solutions were obtained by homo- and heteronuclear NMR methods. These data show
      that the tertiary structure ensembles of C-terminal CCK-8 and CCK-58 differ
      significantly. Thus, distinct solution conformations may explain differences in
      CCK(A) and CCK(B) receptor interactions of large and small molecular forms of
      CCK.

PMID- 12051762
TI  - Rapamycin partially prevents insulin resistance induced by chronic insulin
      treatment.
AB  - Chronic insulin exposure induces serine/threonine phosphorylation and degradation
      of IRS-1 through a rapamycin-sensitive pathway, which results in a down
      regulation of insulin action. In this study, to investigate whether rapamycin (an
      mTOR inhibitor) could prevent insulin resistance induced by hyperinsulinemia, 3T3
      L1 adipocytes were incubated chronically in the presence of insulin with or
      without the addition of rapamycin. Subsequently, the cells were washed and re
      stimulated acutely with insulin. Chronic insulin stimulation caused a reduction
      of GLUT-4 and IRS-1 proteins with a correlated decrease in acute insulin-induced
      PKB and MAPK phosphorylations as well as a reduction in insulin-stimulated
      glucose transport. Rapamycin prevented the reduction of IRS-1 protein levels and
      insulin-induced PKB Ser-473 phosphorylation with a partial normalization of
      insulin-induced glucose transport. In contrast, rapamycin had no effect on the
      decrease in insulin-induced MAPK phosphorylation or GLUT-4 protein levels. These
      results suggest that chronic insulin exposure leads to a down-regulation of PKB
      and MAPK pathways through different mechanisms in adipocytes.

PMID- 12051763
TI  - Ceramide promotes the death of human cervical tumor cells in the absence of
      biochemical and morphological markers of apoptosis.
AB  - C8-ceramide, a synthetic cell-permeable analog of endogenous ceramides,
      interfered with cell proliferation, and was cytotoxic to papilloma virus
      containing human cervix carcinoma cells, CALO, INBL, and HeLa, that match two
      clinical stages of tumor progression. C8-ceramide (3 microM) markedly reduced the
      tumor cell number after 48 h of treatment, an effect that endured even after the
      removal of C8-ceramide. The carcinoma cells showed morphologic changes,
      characteristic of necrosis and released lactate dehydrogenase (LDH). A
      biologically inactive analog C8-dihydro-ceramide had no effect on cell viability
      in any of the cell lines tested. Seventy-two hours after C8-ceramide treatment
      none of the biochemical and morphological markers characteristic of apoptosis:
      (a) nuclear chromatin condensation, (b) DNA fragmentation, (c) proteolysis of the
      caspase-3 substrate poly-(ADP-ribose)-polymerase (PARP), and (d) appearance of
      phosphatidylserine on the external cell membrane, were observed. C8-ceramide had
      no effect on human cervix fibroblasts and induced a mild reduction (30%) in the
      proliferation of normal human cervix epithelia and HeLa cells (IV-B metastatic
      stage). The cytotoxicity of C8-ceramide was restricted to CALO (early II-B) and
      INBL (IV-A non-metastatic) carcinoma cells. The possible application of ceramide
      in the treatment of early stages of cervical cancer is discussed.

PMID- 12051764
TI  - SPAP2, an Ig family receptor containing both ITIMs and ITAMs.
AB  - This study reports cloning and characterization of SPAP2, a novel transmembrane
      protein. The extracellular portion of SPAP2 contains six immunoglobulin-like
      domains and its intracellular segment has two immunoreceptor tyrosine-based
      activation motifs (ITAMs) and two immunoreceptor tyrosine-based inhibition motifs
      (ITIMs). We also identified four alternatively spliced products. Sequence
      alignment with the genomic database revealed that the SPAP2 gene contains 16
      exons and is localized at chromosome 1q21. PCR analyses demonstrated that SPAP2
      mRNA is expressed in restricted human tissues including the kidney, salivary
      gland, adrenal gland, uterus, and bone marrow. Tyrosine-phosphorylated SPAP2 is
      specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70
      and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific
      mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the
      ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692
      and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.
      Finally, recruitment of SHP-1 to the tyrosine-phosphorylated ITIMs led to a
      marked activation of the enzyme.

PMID- 12051765
TI  - Protein Ser/Thr phosphatases PPEF interact with calmodulin.
AB  - Regulation of protein dephosphorylation by cytoplasmic Ca(2+) levels and
      calmodulin (CaM) is well established and considered to be mediated solely by
      calcineurin. Yet, recent identification of protein phosphatases with EF-hand
      domains (PPEF/rdgC) point to the existence of another group of Ca(2+)-dependent
      protein phosphatases. We have recently hypothesised that PPEF/rdgC phosphatases
      might possess CaM-binding sites of the IQ-type in their N-terminal domains. We
      now employed yeast two-hybrid system and surface plasmon resonance (SPR) to test
      this hypothesis. We found that entire human PPEF2 interacts with CaM in the in
      vivo tests and that its N-terminal domain binds to CaM in a Ca(2+)-dependent
      manner with nanomolar affinity in vitro. The fragments corresponding to the
      second exons of PPEF1 and PPEF2, containing the IQ motifs, are sufficient for
      specific Ca(2+)-dependent interaction with CaM both in vivo and in vitro. These
      findings demonstrate the existence of mammalian CaM-binding protein Ser/Thr
      phosphatases distinct from calcineurin and suggest that the activity of PPEF
      phosphatases may be controlled by Ca(2+) in a dual way: via C-terminal Ca(2+)
      binding domain and via interaction of the N-terminal domain with CaM.

PMID- 12051766
TI  - Conformational and molecular modeling studies of sulfated cholecystokinin-15.
AB  - Conformational features of the C-terminal carboxyamidated pentadecapeptide of CCK
      (S(19)HRISDRD[SO(4)]-YMGWMDF(33)-NH(2)) were determined by NMR spectroscopy in a
      zwitterionic membrane-mimetic solvent system, composed of DPC micelles. The C
      terminal octapeptide consisted of a well-defined pseudohelix that was nearly
      identical to the structure previously reported for nonsulfated CCK-8 in the same
      solvent system. N-terminal amino acids of CCK-15 were highly disordered, with no
      clear conformational preference. Extensive NOE-restrained molecular dynamics
      simulations of the CCK-15/CCK(1)-R complex suggested that almost all the
      experimentally determined intermolecular contact points provided by NMR, site
      directed mutagenesis, and photoaffinity labeling could be simultaneously
      satisfied, when the N-terminus of the ligand is placed in close spatial proximity
      to the N-terminus of the receptor.

PMID- 12051767
TI  - Intracellular membrane trafficking pathways in bone-resorbing osteoclasts
      revealed by cloning and subcellular localization studies of small GTP-binding rab
      proteins.
AB  - A variety of intracellular membrane trafficking pathways are involved in
      establishing the polarization of resorbing osteoclasts and regulating bone
      resorption activities. Small GTP-binding proteins of rab family have been
      implicated as key regulators of membrane trafficking in mammalian cells. Here we
      used a RT-PCR-based cloning method and confocal laser scanning microscopy to
      explore the expression array and subcellular localization of rab proteins in
      osteoclasts. Rab1B, rab4B, rab5C, rab7, rab9, rab11B, and rab35 were identified
      from rat osteoclasts in this study. Rab5C may be associated with early endosomes,
      while rab11B is localized at perinuclear recycling compartments and may function
      in the ruffled border membrane turnover and osteoclast motility. Interestingly,
      late endosomal rabs, rab7, and rab9, were found to localize at the ruffled border
      membrane indicating a late endosomal nature of this specialized plasma membrane
      domain in resorbing osteoclasts. This also suggests that late endocytotic
      pathways may play an important role in the secretion of lysosomal enzymes, such
      as cathepsin K, during bone resorption.

PMID- 12051768
TI  - Identification of a KRAB-containing zinc finger protein, ZNF304, by AU-motif
      directed display method and initial characterization in lymphocyte activation.
AB  - A novel human Kruppel-associated box (KRAB) type zinc finger protein encoding
      gene, ZNF304, was obtained by AU-motif-directed display and RACE. This gene,
      which contains a tandem AU motif in the 3' untranslated region, has an ORF 1977
      bp long that codes for a putative 659 residue protein with an amino-terminal KRAB
      domain and 13 carboxyl-terminal C2H2 zinc finger units. The gene maps to
      chromosome 19q13.4, a region that contains the largest zinc finger cluster so far
      identified in the human genome. Structurally, ZNF304 is related to a family of
      repressor transcription factors. ZNF304 expression was higher in lymphoid tissues
      but it was also detected in the following tissues, ordered by abundance: thyroid,
      adrenal gland, prostate, pancreas, and skeletal muscle. Jurkat, U937, and THP1
      cell lines showed a relatively low expression of ZNF304. By contrast, PBLs
      stimulated with PHA or PMA + ionomycin showed a biphasic expression with a sharp
      increase at 6 h. This induction was closely parallel to IFN-gamma expression and
      partially to IL-4 and IL-10. The tissue distribution and kinetics of induction
      suggest that ZNF304 may be involved in the regulation of lymphocyte activation.

PMID- 12051769
TI  - Detection of anti-elongation factor 2 kinase (calmodulin-dependent protein kinase
      III) antibodies in patients with systemic lupus erythematosus.
AB  - Elongation factor 2 kinase (eEF-2K), also known as calmodulin-dependent protein
      kinase III, is a member of the calmodulin-mediated signaling pathway that links
      activation of cell surface receptors to cell division. The activity of eEF-2K is
      increased in many human cancers and may be a valid target for anti-cancer
      treatment. It is one of the unconventional eukaryotic protein kinases with
      respect to its structural domains in comparison to other members of the
      serine/threonine protein kinase superfamily. eEF-2K is highly conserved in
      nature. For example, the amino acid sequence of human eEF-2K is 90% identical to
      mouse and rat eEF-2Ks and 40% identical to that of the C. elegans enzyme.
      Therefore it has been difficult to generate high-titer and high-specificity
      antibodies to the human enzyme by traditional techniques. Patients with systemic
      lupus erythematosus (SLE) produce auto-antibodies to a variety of cellular
      proteins, including members of the protein translation apparatus. Hence, we
      developed an ELISA assay that could detect anti-eEF2K antibodies from sera of SLE
      patients using purified eEF-2K as an antigen. We screened 117 sera from SLE
      patients. High-titer anti-eEF-2K antibodies were detected in 72 subjects. One of
      the high-titer sera was used for further characterization. The auto-antibody
      recognized eEF-2K on immunoblots and immunoprecipitated the kinase with intact
      enzyme activity. In conclusion, anti-eEF-2K antibodies are found in sera of SLE
      patients and are useful tools to study the role of this highly conserved enzyme.

PMID- 12051770
TI  - Hepatobiliary excretion of biliverdin isomers and C10-substituted biliverdins in
      Mrp2-deficient (TR(-)) rats.
AB  - Multidrug resistance protein 2 (Mrp2) is considered the major mammalian membrane
      transporter of non-bile salt organic anions from liver to bile. Using Mrp2
      deficient rats, we show that the protein is not essential for biliary excretion
      of biliverdin, its IIIalpha and XIIIalpha isomers, mesobiliverdin XIIIalpha or
      biliverdins bearing bulky lipophilic groups that are not reduced by biliverdin
      reductase in vivo. Yet, Mrp2 deficiency does retard the biliary excretion of
      these verdins to different degrees. The data indicate that there are Mrp2
      independent mechanisms in the rat for biliary excretion of dicarboxylate organic
      anions related to biliverdin.

PMID- 12051771
TI  - Reconstitution of cleavage of human immunodeficiency virus type-1 (HIV-1) RNAs.
AB  - A human immunodeficiency virus type 1 (HIV-1) particle contains approximately
      1200 molecules of gag proteins and two copies of a 9.2-kb genomic RNA which has
      been reported to be dimerized and rapidly cleaved and to form a complex with a
      nucleocapsid protein, p7 (NCp7), during viral budding. These suggest that the
      cleavage can be reconstituted with gag proteins in vitro. Here we show that the
      p15(gag) coding region of viral RNA is fragmented in viral particles and that in
      vitro-synthesized RNA transcripts of HIV-1 undergo cleavage which is activated by
      NCp7 and other factors. Single-stranded oligoribonucleotides were cleaved between
      C and A or U and A, leaving 2',3'-cyclic phosphate and 5'-hydroxyl termini. These
      findings might explain the rapid degradation of genomic RNAs in HIV-1 particles.

PMID- 12051772
TI  - Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to
      myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared
      to Wistar controls.
AB  - Previous data from our and other labs demonstrated a decreased chiro-inositol
      content in urine and tissues of human subjects and animals with type 2 diabetes.
      In urine this decrease in chiro-inositol was accompanied by an increase in myo
      inositol content. Decreased urine levels of chiro-inositol in monkeys were next
      correlated with the severity of underlying insulin resistance determined by five
      separate assays. To investigate the decreased chiro-inositol and the accompanying
      increased myo-inositol excretions in urine in humans and monkeys, we postulated a
      defect in the epimerization of myo-inositol to chiro-inositol. [(3)H]Myo-inositol
      was then shown to be converted to [(3)H]chiro-inositol in rats in vivo and in
      fibroblasts in vitro in a process stimulated by insulin. We next demonstrated
      that the conversion of [(3)H]myo-inositol to [(3)H]chiro-inositol in vivo was
      markedly decreased in GK type 2 diabetic rats compared to Wistar controls in
      liver, muscle, and fat, insulin sensitive tissues. Decreases of 20-25% conversion
      to baseline levels of under 5% conversion were observed. In the present work, we
      initially compared the total contents of myo-inositol and chiro-inositol in GK
      type 2 diabetic rat kidney, liver, and muscle compared to Wistar controls. We
      demonstrated a consistent decreased total chiro-inositol to myo-inositol ratio in
      kidney, liver, and muscle compared to controls. We next established the presence
      of a myo-inositol to chiro-inositol epimerase activity in rat liver cytosol.
      Enzyme activity was shown to be time and enzyme concentration dependent with a
      broad pH optimum. It required NADH and NADPH for full activity, which is
      compatible with its action via an oxido-reductive mechanism. Lastly, we
      demonstrated that the epimerase enzyme bioactivity was significantly decreased in
      muscle, liver, and fat cytosolic extracts of GK type 2 diabetic rats versus
      Wistar controls. Decreased myo-inositol to chiro-inositol epimerase activity may
      therefore play a role in explaining the decreased chiro-inositol to myo-inositol
      urine and tissue ratios observed here and in previous animal and human studies.
      Further it may also possibly play a role in the underlying insulin resistance.

PMID- 12051773
TI  - E-selectin modulates the malignant properties of T84 colon carcinoma cells.
AB  - The extravasation of metastatic cells is regulated by molecular events involving
      the initial adhesion of tumor cells to the endothelium and subsequently the
      migration of cells in the host connective tissue. E-selectin on endothelial cells
      and sialyl Lewis X carbohydrate component on tumor cells are mainly involved in
      the adhesion of colon carcinoma cells to the endothelium of target organ.
      Interaction of T84 colon cancer cells to purified E-selectin in vitro caused an
      increase in the tyrosine phosphorylation of a number of proteins as well as the
      modulation of cellular properties correlated to the metastatic phenotype.
      Specifically, E-selectin-stimulated actin reorganization, increased collagenase
      secretion, and induced cell migration. Treatment of T84 cells with herbimycin A
      inhibited cell adhesion as well as selectin-induced increase of cell migration,
      and cytoskeleton assembly. Our data demonstrate that binding of cancer cells to E
      selectin starts signal transduction pathways which may affect the tumor
      metastatic abilities.

PMID- 12051774
TI  - Acid-labile formylation of amino terminal proline of human immunodeficiency virus
      type 1 p24(gag) was found by proteomics using two-dimensional gel electrophoresis
      and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry.
AB  - HIV-1(LAV-1) particles were collected by ultracentrifugation, treated with
      subtilisin, and then purified by Sepharose CL-4B column chromatography to remove
      microvesicles. The lysate of the purified human immunodeficiency virus type 1
      (HIV-1) particles was subjected to two-dimensional (2D) gel electrophoresis and
      stained, and the stained spots were excised and digested with trypsin. The
      resulting peptide fragments were characterized by matrix-assisted laser
      desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Twenty
      five proteins were identified as the proteins inside the virion and the acid
      labile formyl group of an amino terminal proline residue of HIV-1(LAV-1) p24(gag)
      was determined by MALDI-TOF MS before and after weak-acid treatments (0.6 N
      hydrochloric acid) and confirmed by post-source decay (PSD) of the N-formylated N
      terminal tryptic peptide (N-formylated Pro(1)-Arg(18)). The role of formylation
      has been unclear so far, but it is surmised that the acid-labile formylation of
      HIV-1(LAV-1) p24(gag) may play a critical role in the formation of the HIV-1 core
      for conferring HIV-1 infectivity.

PMID- 12051776
TI  - A role of EphB4 receptor and its ligand, ephrin-B2, in erythropoiesis.
AB  - Erythropoiesis is regulated not only by erythropoietin but also by
      microenvironments which are composed of transmembrane molecules. We have
      previously shown that a receptor tyrosine kinase EphB4 is predominantly expressed
      on human erythroid progenitors in bone marrow. EphB4 is expressed in
      approximately 45% of hematopoietic progenitor cells, which are CD34-positive and
      c-Kit-positive in human umbilical cord blood (hUCB). The transmembrane ligand for
      EphB4 or ephrin-B2 is expressed on bone marrow stromal cells and arterial
      endothelial cells. When such EphB4-positive hematopoietic progenitor cells were
      co-cultured with stromal cells which express ephrin-B2, they were immediately
      detached from stromal cells and differentiated to mature erythroid cells. At that
      time, expression of EphB4 immediately down-regulated. In contrast, on ephrin-B2
      non-expressing stromal cells, they remained EphB4-positive cells and the
      generated number of mature erythroid cells was less than that on ephrin-B2
      expressing stromal cells. Additionally, ephrin-B2 expression on endothelial cells
      up-regulated under hypoxic condition. Taken together, we propose that one of the
      molecular cues that regulate erythropoiesis is ephrin-B2 on stromal cells.

PMID- 12051775
TI  - Daily melatonin supplementation in mice increases atherosclerosis in proximal
      aorta.
AB  - Considerable evidence supports the hypothesis that LDL oxidation plays an
      important role in atherosclerosis. Even though high melatonin doses inhibit LDL
      oxidation in vitro, the effect of melatonin on atherosclerosis has never been
      studied. We have demonstrated that the feeding of hypercholesterolemic mice with
      an atherogenic diet supplemented with melatonin highly increases the surface of
      atherosclerotic lesions in the proximal aorta. These observations occur without
      detectable lipidic or glucidic phenotype alteration. Melatonin treatment
      increased highly the sensitivity of atherogenic lipoprotein to Cu(2+) and gamma
      radiolysis generated oxyradical ex vivo oxidation during the fasting period.
      Moreover, these altered lipoproteins were less recognized by the LDL receptor
      metabolic pathway of murine fibroblasts while they transferred many more
      cholesteryl esters to murine macrophages. This study suggests that caution should
      be taken as regards high melatonin dosage in hypercholesterolemic patients.

PMID- 12051777
TI  - An essential role for REV3 in mammalian cell survival: absence of REV3 induces
      p53-independent embryonic death.
AB  - The REV3 gene of budding yeast encodes the catalytic subunit of DNA polymerase
      zeta that carries out translesion DNA synthesis. While REV3-null yeast mutants
      are viable and exhibit normal growth, Rev3-deficient mice die around midgestation
      of embryogenesis, which is accompanied by massive apoptosis of cells within the
      embryo proper. We have investigated whether REV3 is required for the survival of
      mouse cells and whether the embryonic lethality caused by REV3 deficiency can be
      rescued by introduction of a Rev3 transgene or by inactivation of p53, the
      cellular gatekeeper that regulates DNA damage-induced apoptosis. We show that
      Rev3(-/-) blastocysts were unable to survive and grow in culture but expression
      of a Rev3 transgene restored their outgrowth. Moreover, Rev3 transgene expression
      suppressed the apoptosis in E7.5 Rev3(-/-) embryos. The Rev3(-/-) embryonic
      lethality, however, was not rescued by either Rev3 transgene expression or p53
      deficiency. These results reveal an essential role for REV3 in the survival and
      growth of mammalian cells and suggest that Rev3(-/-) embryonic death occurs in a
      p53-independent pathway.

PMID- 12051778
TI  - Leptin receptors, NPY, and tyrosine hydroxylase in autonomic neurons supplying
      fat depots in a pig.
AB  - The goal of this study was to determine the immunohistochemical characteristics
      of peripheral adrenergic OBR-immunoreactive (OBR-IR) neurons innervating adipose
      tissue in a pig. The retrograde tracer, Fast Blue (FB), was injected into either
      the subcutaneous, perirenal, or mesentery fat tissue depots of three male and
      three female pigs each with approximately 50 kg body weight. Sections containing
      FB(+) neurons were stained for OBR, tyrosine hydroxylase (TH) or neuropeptide Y
      (NPY) using a double labeling immunofluorescence method. OBR, TH, and NPY
      immunoreactivities were present in the thoracic (T) and lumbar (L) ganglia of the
      sympathetic chain, as well as in the coeliac superior mesenteric ganglion (CSMG),
      inferior mesenteric ganglion (IMG), intermesenteric ganglia (adrenal-ADG,
      aorticorenal-ARG, and ovarian-OG or testicular-TG ganglion). These results
      indicate that, in addition to neuroendocrine functions, leptin may affect
      peripheral tissues by acting on receptors located in sympathetic ganglion
      neurons.

PMID- 12051779
TI  - Neurodevelopmental investigations among methylmercury-exposed children in French
      Guiana.
AB  - French Guiana, like its neighbors, suffers from environmental pollution with
      methylmercury from gold mining activities, and Amerindian communities are
      particularly affected. A neurological and a neurospsychological evaluation were
      carried out in children of three Amerindian communities with various levels of
      pollution: 156 children from the Upper Maroni (high exposure), 69 from Camopi on
      the Oyapock river (median exposure), and 153 from Awala on the Atlantic coast
      (low exposure). Exposure to methylmercury was measured by determination of total
      mercury in the hair of the children and their mothers (geometric mean, 12.7
      microg/g in Upper Maroni). No major neurologic signs were observed in the
      children examined. After adjustment for potential confounders, we found a dose
      dependent association between maternal hair mercury level and increased deep
      tendon reflexes, poorer coordination of the legs, and decreased performance in
      the Stanford-Binet Copying score, which measures visuospatial organization. In
      this last test, the frequency of rotation errors was high in the 5-6 years age
      group and increased with mercury exposure. These associations depended on the sex
      of child and were stronger among boys. The interpretation of these results is
      limited mainly by the cross-sectional design of the study. It identifies specific
      neurological and neuropsychological deficits, in some cases modulated by sex,
      which are consistent with known targets of mercury neurotoxicity.

PMID- 12051780
TI  - Relationship between blood lead concentrations and learning achievement among
      primary school children in Taiwan.
AB  - Over the past 20 years lead has been proven to exert an influence on the
      intelligence of children. Especially for children exposed to environmental lead,
      average blood lead was often lower than the officially recognized intoxication
      level. Because Kaohsiung is an industrial area in Taiwan and lead exposure is an
      important environmental issue, we attempted to ascertain the extent to which
      environmental lead influences the achievement of primary school children. We
      randomly selected 934 children from 32 primary schools in 11 districts of
      Kaohsiung City. Blood lead levels of the children were checked, and they were
      administered a questionnaire about their family information. Scores of several
      courses were used in this study on the relationship between a child's blood lead
      and his or her academic performance (Ranking with his or her classmates),
      including Chinese (reading and writing short Chinese articles), Mathematics,
      History and Society, and Natural Science. Multiple regression models were done
      with adjustments for the confounding effects of their parents' socioeconomic
      levels. The mean (SD) of 934 blood lead level was 5.50 (1.86) microg/dL.
      Spearman's coefficient showed that class rankings in Chinese, Mathematics,
      Natural Science, and History and Society were all strongly associated with blood
      lead levels (P<0.01). The multiple regression models revealed that blood lead
      level exerts a stronger influence on children's language ability (Chinese) than
      on their ability to calculate (Mathematics). Our results suggest that
      environmental lead exposure adversely affects a child's academic achievement,
      making a direct link between exposure to lead and academic attainment.

PMID- 12051781
TI  - Identification of sport fish consumption patterns in families of recreational
      anglers through factor analysis.
AB  - This paper reports on the identification of sport fish consumption patterns in
      angler families through the factor analysis technique. New York State
      recreational anglers and their spouses or partners were surveyed in 1991 about
      their consumption of Lake Ontario and Lake Erie sport fish. Respondents were
      surveyed again in 1997 to report the number of sport fish consumed by their
      children aged 5-10 years. Parental report revealed that 60% of children had
      consumed at least one sport fish meal over their lifetime. Anglers', partners',
      and children's variables were entered into three separate factor analysis models
      to assess consumption patterns. Factors for anglers and partners accounted for 65
      and 59% of variance in consumption scores, respectively. Factors dealing with
      trout and salmon consumption accounted for the most variance. Children's factors
      accounted for 82% of variance in consumption scores, showing separation in
      relation to type of fish, body of water, and age at consumption. Children's
      factors were then used as dependent measures of separate multiple regression runs
      in which parental factors were entered stepwise as predictors. Significant
      associations between parental and children's factors were noted, suggesting that
      sport fish consumption patterns in parents are predictive of similar consumption
      patterns in children. Results suggest that sport fish consumption advisories do
      not fully prevent consumption of contaminated sport fish during childhood.
      Therefore, risk communicators may need to modify the current strategy of
      informing anglers and their families about sport fish consumption
      recommendations.

PMID- 12051782
TI  - Short-term effects of low-level air pollution on respiratory health of adults
      suffering from moderate to severe asthma.
AB  - Only a few studies have been carried out on the health effects of air pollution
      on patients suffering from severe asthma. We wanted to test the sensitivity of
      these patients to Paris air pollution. During 13 months, 60 severe asthmatics (62
      female; mean age 55 years) were monitored by their physician, who filled in a
      follow-up form at each consultation and reported any asthma attacks. Daily levels
      of SO(2), PM10, NO(2), and O(3) were provided by the air quality network.
      Statistical analysis (generalized estimating equation models that accounted for
      autocorrelation of responses, temporal, meteorological, and aerobiological
      variables, and some individual characteristics) revealed significant associations
      between PM10, O(3), and incident asthma attacks. Odds Ratio (OR) for an increase
      of 10 microg/m(3) of PM10 was 1.41; 95% confidence interval (CI) [1.16; 1.71]. An
      increase of 10 microg/m(3) of O(3) was significantly associated with asthma
      attacks; OR=1.20; 95% CI [1.03; 1.41]. These relations were observed after a
      delay between exposure and asthma attacks of 3 to 5 days for PM10 and 2 days for
      O(3), and they tended to differ according to atopic status. The results of our
      study suggest that ambient Paris levels of PM10 and O(3) affected health of
      severe asthmatics, despite their treatment.

PMID- 12051783
TI  - Biotransformation of formaldehyde in cultured human bronchus.
AB  - Biotransformation of formaldehyde to formic acid was studied to investigate the
      capacity of human bronchial epithelial cells to detoxicate formaldehyde. Normal
      human bronchial explants and normal primary bronchial epithelial cells were grown
      in medium containing 0.5 to 5 mM formaldehyde for up to 48 h. Formic acid was
      quantitated by analytical isotachophoresis. Explants were cultured with up to 5
      mM formaldehyde for 48 h with approximately linear turnover, but at 5 mM the
      cells showed reduced biotransformation relative to the lower concentrations. The
      mean K(m) values for explants were 1.4 and 5.1 mM for cells and the mean V(max)
      values were 3.3 nmol/mg protein.min for the explants and 6.1 nmol/mg protein.min
      for the cells. By using the same technique with hepatocytes we found K(m) 1.25 mM
      and V(max) 4.2 nmol/mg protein.min, indicating that human bronchial epithelium
      cells have formaldehyde biotransforming activity similar to that of hepatocytes.
      Our results indicate that human bronchial epithelial cells oxidize formaldehyde
      at a relatively fast rate at concentrations up to 3 mM formaldehyde in the medium
      over a period up to 48 h.

PMID- 12051784
TI  - Survey of some heavy metals in sediments from vehicular service stations in
      Jordan and their effects on social aggression in prepubertal male mice.
AB  - Vehicle services create the potential for heavy metal accumulation in the working
      environment. This study assessed five vehicle services, namely body repair, oil
      exchange, mechanical repair, tire repair, electrical repair, and washing services
      for three types of vehicles: airplanes, buses, and cars. The results show that
      there are significant increases in the total contents of Fe, Cu, Pb, Zn, Ni, Mn,
      and Cr in ambient dust, with Fe being the highest and Cr the lowest. The main
      cause of the presence of these elements is due to the metals' corrosion from
      vehicle sources and petroleum residue. Variations in the concentrations with the
      type of service and within the same service at different locations were observed.
      In this study, the exposure of prepubertal male mice to industrial metal salts in
      drinking water at a concentration of 1000 ppm for 90 days was investigated.
      Exposure of male mice to lead acetate significantly reduced the social aggression
      of the resident untreated subjects. Additionally, this treatment resulted in
      decreasing weights of body, testes, preputial glands, and seminal vesicles. In
      comparison, no such effects were seen in mice given copper chloride or manganese
      chloride. The results show that only lead acetate produced a pattern of responses
      clearly indicative of altered gonadal function.

PMID- 12051785
TI  - A comparison of household lead exposure assessment methods in an old, urban
      community.
AB  - The accurate assessment of lead hazards within the household is critical to the
      prevention of lead exposure to children living in urban communities. Although
      dust wipes are currently accepted as the best method of assessing lead hazards,
      questionnaires and visual inspections are also used. This study evaluates the
      level of agreement among these three methods of assessment using a sample of 126
      women living in old, urban houses. The level of agreement was assessed using the
      kappa statistic, which adjusts for chance agreement. Overall, the kappa results
      for both the participant's assessment (questionnaire) and the visual inspector's
      assessment were low, indicating only slight to moderate agreement with the dust
      lead wipe levels. Kappas were higher and more consistent for the visual
      inspector's assessment than for the participant's assessment. These results
      indicate that visual inspections and participant questionnaires may provide less
      accurate information regarding lead hazards within the household than dust wipes.
      Because lead hazard recognition is important in the prevention of lead exposure
      in children, our data suggest that emphasis should be placed on the measurement
      of dust lead levels directly in assessing household lead hazards, possibly by
      teaching women in high-risk neighborhoods to take dust samples themselves.

PMID- 12051786
TI  - Airborne fungi and endotoxin concentrations in different areas within textile
      plants in Taiwan: a 3-year study.
AB  - Bioaerosols have been found in many occupational environments, including animal
      feeding houses, poultry slaughter houses, and cotton textile plants. This study
      was undertaken to examine a group of bioaerosols, the endotoxins, fungi, and
      bacteria, inside two textile factories over 3 years in Taiwan, where temperature
      and humidity are usually high year-round. Airborne dust was collected with filter
      cassettes attached to personal pumps and analyzed by the Kinetic Limulus Assay
      with Resistant-parallel-line Estimation. For fungi and bacteria determination,
      samples were collected using duplicated single-stage impactors, and organisms
      were counted after incubation. Endotoxin was the major contamination inside
      textile plants. Indoor levels were substantially higher than outdoor
      concentrations by 63- to 278-fold. The average values of fungi inside and outside
      the plants were not significantly different. Airborne bacteria levels were higher
      inside the plants as compared to outside. The carding sites, using only cotton,
      had extremely high endotoxin levels, greater than those at sites using synthetic
      fibers. Cotton, may be a major source of endotoxin contamination. In conclusion,
      the early stage of textile processing seems to generate high endotoxin and
      bacteria contamination. Priorities should be given to occupational hygiene
      programs for workers at various sites in textile plants.

PMID- 12051787
TI  - Particulate matter and particle-attached polycyclic aromatic hydrocarbons in the
      indoor and outdoor air of Tokyo measured with personal monitors.
AB  - Using two types of personal monitors for suspended particulate matter of diameter
      under 10 microm (PM-10) and for particles of diameter under 1 microm with
      attached polycyclic aromatic hydrocarbons (PPAH), we measured the PM-10 and PPAH
      concentrations in the indoor and outdoor air in various locations in the Tokyo
      area. The major findings were as follows. (1) The PPAH concentrations in a clean
      living room increased rapidly within several minutes after one cigarette was
      smoked. (2) Using the average indoor concentrations of PM-10 and PPAH in a
      department store as control concentrations, respectively, where the average
      indoor PM-10 concentration was closest to an annual average outdoor concentration
      in Japan, the mean value for indoor air concentrations of PM-10 by location
      ranged from 2.2 to 6.2 times the control concentration, and the mean value for
      indoor air concentrations of PPAH by location ranged from 1.0 to 32.2 times the
      control concentration. (3) Using the same control concentrations, the mean value
      of outdoor concentrations of PM-10 by location ranged from 1.6 to 8.5 times the
      control concentration, while the mean value of outdoor concentrations of PPAH by
      location were up to 353.7 times the control concentration. The major polluted
      places were main traffic roads, highways, and street tunnels. (4) The correlation
      coefficient between the PM and the PPAH concentrations in the total monitoring
      time was 0.014, which was not significant (P>0.05).

PMID- 12051788
TI  - Trace elements in blood and serum of Swedish adolescents: relation to gender,
      age, residential area, and socioeconomic status.
AB  - The influence of gender, age, residential area, and socioeconomic status on the
      blood and serum levels of 13 trace elements was studied in boys and girls living
      in two Swedish cities with different socioeconomic and environmental characters.
      The same groups of adolescents were sampled twice, at ages 15 (n=372) and 17
      (n=294) years. All the investigated factors were shown to be of importance. Age
      was important for most elements; e.g., copper levels in both blood and serum
      increased in girls, and selenium increased in serum from both genders. Lead
      decreased approximately 10% in blood from the first to the second sampling, and
      cadmium increased in blood, however not in nonsmokers. The age factor may also
      reflect temporal changes in environmental exposure, especially for nonessential
      elements. Girls had higher levels of cobalt and copper, while lead in blood was
      higher in boys. Smoking girls had higher copper levels than nonsmoking girls.
      Residential area influenced all elements. The teenagers with university-educated
      mothers had higher levels of cadmium in blood than those with only primary school
      educated mothers.

PMID- 12051789
TI  - Metal levels in fish from the Savannah River: potential hazards to fish and other
      receptors.
AB  - Fish are ideal indicators of heavy metal contamination in aquatic systems because
      they occupy different trophic levels and are different sizes and ages. In this
      paper, we report concentrations of arsenic, cadmium, chromium, copper, lead,
      manganese, strontium(88) and mercury in the muscle of 11 species of fish from the
      Savannah River near the Savannah River Site. We test the hypotheses that there
      are no locational, species, or trophic-level differences in contaminant levels.
      There were significant species differences for all metals; higher-trophic-level
      fish generally had higher levels of arsenic, chromium, and copper. There were
      relatively few locational differences, and where there were such differences,
      they were small. The relationships between body weight and contaminant levels
      were generally positive, except for strontium, where there was a negative
      correlation for bowfin (Amia cal va), bass (Micropterus salmoides), yellow perch
      (Perca flavescens), and shellcracker (Lepomis microlophus) and no relationship
      for the other species. The levels of most metals were similar to, or lower than,
      those for the United States generally, and the levels of metals in fish from the
      Savannah River do not appear to pose a health threat to the fish themselves or to
      higher-order consumers, based on levels known to cause effects.

PMID- 12051791
TI  - Is DDT exposure during fetal period and breast-feeding associated with
      neurological impairment?
AB  - The concentration of certain persistent organic pollutants was determined in a
      family including both parents and one son with neurological impairment suggested
      to be Attention Deficit-Hyperactivity Disorder (ADHD). For comparison control
      subjects from other ongoing studies were used. They were of the same sex and age
      group as the respective family member. For polychlorinated biphenyls,
      hexachlorobenzene, and chlordanes similar results were found in the study groups.
      The concentration of DDE, the main metabolite of DDT, was increased in the
      mother, 782 ng/g lipid, compared with mean 403, median 259 (range 51-1354) for
      the female controls. Also, the son had an increased concentration of 259 ng/g
      lipid, compared with mean 104, median 72 (range 46-349) for controls. A low
      concentration was found in the father, 127 ng/g lipid. As a child and as a
      teenager to the age of 17, the mother was exposed to DDT in her home environment.
      We discuss the potential of fetal and breast-feeding exposure of the son.
      Neurodevelopmental impairment has been reported for dioxins and PCBs, but DDT
      seems to have been less investigated in this respect.

PMID- 12051792
TI  - Metals and women's health.
AB  - There is a lack of information concerning whether environmental-related health
      effects are more or less prevalent or manifested differently in women compared to
      men. Previously, most research in the area of toxicology and environmental and
      occupational health involved male subjects. The present work aims at reviewing
      exposure and health effects of cadmium, nickel, lead, mercury, and arsenic
      manifested differently in women than in men. The gender difference in exposure to
      nickel results in a much higher prevalence of nickel allergy and hand eczema in
      women than in men. The internal cadmium dose is generally higher in women than in
      men, due to a higher gastro-intestinal absorption at low iron stores. This was
      probably one major reason why Itai-itai disease was mainly a woman's disease.
      Yet, data are sparse regarding the risk for women relative to men to develop
      cadmium-induced kidney damage in populations exposed to low levels of cadmium.
      Lead is accumulated mainly in bone and increased endogenous lead exposure has
      been demonstrated in women during periods of increased bone turnover, e.g.,
      menopause. Both lead and mercury exposure in pregnant women has to be kept low in
      order to prevent neurodevelopment effects in the developing fetus and child.
      Limited data indicate that women are more affected than men following exposure to
      methylmercury at adult age, while males seem to be more sensitive to exposure
      during early development. Regarding arsenic, some data indicate gender
      differences in the biotransformation by methylation, possibly also in
      susceptibility to certain arsenic-related cancers. Obviously, gender-related
      differences in exposure and health effects caused by metals are highly neglected
      research areas, which need considerable focus in the future.

PMID- 12051794
TI  - Environmental lead contamination in the Rudnaya Pristan--Dalnegorsk mining and
      smelter district, Russian far East.
AB  - A preliminary survey of a remote mining and smelting region of the Russian Far
      East (RFE) indicates significant soil lead contamination and a high probability
      of childhood lead poisoning. Lead concentrations in residential gardens (476-4310
      mg/kg, Gmean=1626 mg/kg) and in roadside soils (2020-22900 mg/kg, Gmean=4420
      mg/kg) exceed USEPA guidance for remediation. Preliminary biokinetic estimates of
      mean blood levels suggest that preschool children are at significant risk of lead
      poisoning from soil/dust ingestion with levels predicted to average 13-27
      microg/dl. Samples of other pathways, such as air, water, paint, interior dust,
      and garden produce, and pediatric and occupational blood lead levels are needed.
      An assessment of the industry's ability to improve emissions controls and
      materials handling should also be undertaken. Global lessons in remediating
      contamination problems and preventing childhood lead poisoning must be applied in
      innovative ways to meet the logistical, social, and economic challenges in the
      RFE.

PMID- 12051793
TI  - Association between renal dysfunction and mortality among inhabitants in the
      region around the Jinzu River basin polluted by cadmium.
AB  - A follow-up study was conducted on 5725 inhabitants (men 2858, women 2867) in and
      around the Jinzu River basin to determine the influence of environmental Cd
      exposure on mortality. In the Jinzu River basin, standardized mortality ratios
      (SMRs) investigated according to urinary findings (protein, glucose, and
      protein+glucose) were significantly low in the urinary protein-, glucose-, and
      protein+glucose-negative groups. SMRs calculated after dividing urinary protein-
      and glucose-positive status into two levels were lowest in the proteinuria- and
      glycosuria-negative groups and tended to be high in the higher positive groups.
      In the Jinzu River basin, Cox's hazard ratios were significantly higher for men
      and women in the urinary protein, glucose and protein+glucose-positive-groups. In
      the same analysis where the urinary protein- and glucose-positive subjects were
      divided into two levels, mortality was demonstrated to be higher in the groups
      with the greater degrees of proteinuria and glycosuria. In the Jinzu River water
      system almost all SMRs and Cox's hazard ratios showed statistical significance.
      This was not the case in the other water systems. Mortality of inhabitants with
      Cd-induced renal injury is increased in the Jinzu River basin.

PMID- 12051795
TI  - Levels of dichlorodiphenyltrichloroethane and deltamethrin in humans and
      environmental samples in malarious areas of Mexico.
AB  - Mexico used dichlorodiphenyltrichloroethane (DDT) to control malaria until 1999,
      when it was replaced with deltamethrin for mosquito control. Thus, we performed
      environmental and exposure assessments to DDT and deltamethrin in the states of
      Chiapas and Oaxaca. In Chiapas, samples were obtained at the time when DDT was
      being used in the malaria control program, while in Oaxaca, samples were
      collected 2 years after the final spraying of DDT and 2 days after deltamethrin
      application. Mean concentrations of DDT and Dichlorodiphenyldichloroethylene
      (DDE), as measured in whole blood, were 67.8 and 86.7 microg/L for children
      living in Chiapas and 27.1 and 60.8 microg/L for adults, respectively. As
      expected, DDT levels were lower 2 years after the final application in Oaxaca
      (20.4 and 13.2 microg/L for children and adults, respectively). Sprayers in
      Chiapas had the highest levels of exposure, with 165.5 and 188.4 microg/L of DDT
      and DDE, respectively. Women living in Chiapas and Oaxaca also had significantly
      higher blood levels of DDT and DDE than those women living in areas where less
      DDT had been used. Deltamethrin exposure was assessed only in children living in
      Oaxaca; 50% of the exposed group had urinary levels of 3-phenoxybenzoic acid
      above the limit of detection (LOD) and 6% had levels above 25 microg/L (five
      times the LOD), with a negative trend with age (r=-0.33). In Chiapas we found
      higher DDT and DDE levels in soil than in Oaxaca. In the latter location, large
      amounts of DDT and DDE were found in sediment samples and deltamethrin was
      detected in indoor soil samples. Considering the environmental data, the blood
      level results can be explained by soil/dust ingestion, human milk ingestion, and
      consumption of fish and other contaminated foods.

PMID- 12051796
TI  - An ecologic study of nitrate in municipal drinking water and cancer incidence in
      Trnava District, Slovakia.
AB  - Contamination of drinking water by nitrate is an evolving public health concern
      since nitrate can undergo endogenous reduction to nitrite, and nitrosation of
      nitrites can form N-nitroso compounds, which are potent carcinogens. We conducted
      an ecologic study to determine whether nitrate levels in drinking water were
      correlated with non-Hodgkin lymphoma and cancers of the digestive and urinary
      tracts in an agricultural district (Trnava District; population 237,000) of the
      Slovak Republic. Routinely collected nitrate data (1975-1995) for villages using
      public water supplies were computerized, and each village was categorized into
      low (0-10 mg/L), medium (10.1-20 mg/L), or high (20.1-50 mg/L) average levels of
      total nitrate in drinking water. Observed cases of cancer in each of these
      villages were ascertained through the district cancer registry for the time
      period 1986-1995. Standardized incidence ratios (SIRs) and 95% confidence
      intervals (CI) for all cancer and selected cancer sites were calculated by
      indirect standardization using age- and sex-specific incidence rates from the
      entire district. For all cancer in women, SIRs increased from villages with low
      (SIR=0.87; 95% CI 0.72-0.95) to medium (SIR=1.07; 95% CI 1.00-1.13) to high
      (SIR=1.14; 1.06-1.22) levels of nitrate (P for trend <0.001); there was a similar
      trend for all cancer in men from low (SIR=0.90; 95% CI 0.81-0.99) to medium
      (SIR=1.08, 95% CI 1.02-1.16), but not for high (SIR=0.94; 0.88-1.02), nitrate
      levels (P for trend <0.001). This pattern in the SIRs (from low to high nitrate
      level) was also seen for stomach cancer in women (0.81, 0.94, 1.24; P for
      trend=0.10), colorectal cancer in women (0.64, 1.11, 1.29; P for trend <0.001)
      and men (0.77, 0.99, 1.07; P for trend=0.051), and non-Hodgkin lymphoma in women
      (0.45, 0.90, 1.35; P for trend=0.13) and men (0.25, 1.66, and 1.09; P for
      trend=0.017). There were no associations for kidney or bladder cancer. These
      ecologic data support the hypothesis that there is a positive association between
      nitrate in drinking water and non-Hodgkin lymphoma and colorectal cancer.

PMID- 12051797
TI  - Interleukin-8 secretion from monocytic cell lines for evaluation of the
      inflammatory potential of organic dust.
AB  - The potential of organic dust to induce inflammation in vitro can be viewed as a
      crude measure of the total biologically active compounds in a dust sample. The
      purpose of this study was to further develop an in vitro screening method for
      evaluation of potential hazard related to low doses of dust exposure using two
      monocytic cell lines (U937 and THP-1). Dust was obtained from schools in
      Copenhagen. U937 and THP-1 cells were stimulated with dust for 24 h and
      interleukin-8 secretion was measured. The initial slopes of the dose-response
      curves were used to calculate the inflammatory potential, or potency factor (PF),
      of the samples. In characterization of the method, lipopolysaccharide from
      Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella
      enteritidis were tested together with three glucans, nickel sulfate (NiSO(4)),
      methyl methacrylate (MMA), formaldehyde, and four surfactants. The PF values of
      LPSs in both monocytic assays ranked as follows: S. enteritidis> E. coli>K.
      pneumoniae/P. aeruginosa. The PF values of NiSO(4), MMA, formaldehyde, and the
      surfactants were zero or below. Using the THP-1 cell line, the PF values of dust
      samples were 30 times higher than when using the U937 cell line, and 7 times
      higher than when using the lung epithelial cell line (A549). The high sensitivity
      of the THP-1 bioassay makes it potentially useful as a screening tool for hazard
      evaluation of dust from, e.g., the indoor environment.

PMID- 12051798
TI  - Interleukins 2 and 12 produce recovery of cytotoxic function in tributyltin
      exposed human natural killer cells.
AB  - Cytotoxic function of human natural killer (NK) cells is modulated by a variety
      of cytokines. Interleukins (IL) 2 and 12 are both potent stimulators of NK cell
      cytotoxic function. Tributyltin (TBT) is used in a variety of consumer products
      and industrial applications. TBT is found in dairy products, meat, and fish. We
      and others have shown that there are measurable levels of TBT in human blood.
      Butyltins appear to increase the risk of cancer and viral infections in exposed
      individuals. We have demonstrated that the ability of NK cells to kill tumor
      cells is greatly diminished after a l-h exposure to TBT and that this inhibition
      persists even after removal of the compound. In the current study we examine the
      effects of the NK-stimulatory ILs, IL2 and IL12, on the ability of NK cells to
      recover from the persistent inhibitory effects of a 1-h TBT treatment. Highly
      purified NK cells (> 95% CD16(+)) or a lymphocyte preparation containing both T
      lymphocytes and NK cells were treated with 300 nM TBT and then allowed to recover
      for 24 h, 48 h, 4 days, and 6 days in TBT-free media containing no interleukin,
      1000 U/mL IL2, 20 ng/mL IL l2, or a combination of IL2 plus IL12. Tumor killing
      function was then tested using a radioactive chromium release assay. As seen in
      our previous studies there is no recovery of NK cell cytotoxic function even
      after a 6-day recovery period when no interleukin is present in the medium.
      However, there is significant recovery of NK cytotoxic function when IL2, IL12,
      or the combination of IL2 plus IL12 is present in the medium during the recovery
      period.

PMID- 12051799
TI  - Distribution of organobrominated and organochlorinated contaminants in Belgian
      human adipose tissue.
AB  - We have measured the levels of flame retardants, polybrominated diphenyl ethers
      (PBDEs), in 20 recent human adipose tissues from Belgium and compared them to
      other organohalogen compounds such as polychlorinated biphenyls (PCBs),
      hexachlorobenzene, 2,2-bis(4-chlorophenyl)-1,1,1-trichloroethane (p,p'-DDT), and
      its metabolite, 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE). After
      Soxhlet extraction and cleanup on acidified silica solid-phase extraction
      cartridges, analysis was achieved by capillary gas chromatography/electron impact
      mass spectrometry. The method allowed the determination of 5 PBDE and 35 PCB
      congeners. Concentrations of PBDEs (sum of congeners IUPAC Nos. 28, 47, 99, 100,
      and 153) ranged between 2.2 and 11.7 ng/g lipid weight and were on the lower end
      of reported PBDE concentrations in European countries. The median value for the
      sum of PCBs (35 congeners) was 841 ng/g lipid weight and ranged from 286 to 1802
      ng/g lipid weight. The median value for the sum of DDTs (calculated from p,p'-DDE
      and p,p'-DDT) was 290 ng/g lipid weight and ranged from 47 to 2802 ng/g lipid
      weight. The sum of PCBs showed a good correlation with the sum of DDTs (r=0.77,
      P<0.05), while the correlation with the sum of PBDEs was weaker (r=0.56, P<0.05).
      No age dependency was found for PBDEs (r=0.09), while PCBs and DDTs showed higher
      correlation coefficients with age (r=0.59 and 0.40, respectively, P<0.05).

PMID- 12051800
TI  - Are 24-hour urine samples and creatinine adjustment required for analysis of
      inorganic arsenic in urine in population studies?
AB  - Compliance with 24-h urine samples can be low in population-based studies and
      first morning void urine samples are often collected for convenience.
      Interpretation of arsenic concentrations in urine is influenced by a range of
      factors unrelated to exposure. To reduce the influence of such factors,
      creatinine adjustment is routinely used. This study aimed to determine whether
      first morning void urinary inorganic arsenic concentrations approximate 24-h
      urinary arsenic concentrations and whether creatinine adjustment improved the
      correlation between environmental arsenic concentrations and urinary inorganic
      arsenic concentrations. One hundred sixty spot samples and corresponding 24-h
      urine samples were collected from people living in areas with a range of
      environmental arsenic concentrations and analyzed for inorganic arsenic using
      borohydride arsine generation followed by atomic absorption spectrophotometry.
      There were no significant differences between the urinary inorganic arsenic
      concentrations for the different sample types or whether creatinine adjusted or
      not. Significant correlations were observed between adjusted and unadjusted
      samples. The data set was highly skewed and when only detectable arsenic samples
      were considered, the relationship between sample types became nonsignificant. The
      results of this study suggest that spot samples may be adequate for measuring
      short-term exposure, using inorganic arsenic as the outcome variable; however,
      additional work on a larger data set is required. Creatinine adjustment of
      urinary inorganic arsenic concentrations may not be required in population
      studies investigating environmental exposure.

PMID- 12051801
TI  - Mixture toxicity of zinc, cadmium, copper, and lead to the potworm Enchytraeus
      albidus.
AB  - Central composite designs were used to develop surface response relationships for
      predicting the chronic toxicity of mixtures of zinc, cadmium, copper, and lead to
      the potworm Enchytraeus albidus. Surface response relationships were obtained for
      all binary mixtures of zinc, cadmium, copper, and lead as well as for mixtures
      with all four metals. For the binary mixture of zinc and cadmium, this approach
      and the toxit unit approach gave similar results. However, with the toxit unit
      approach no such surface response models can be developed. The experimental
      results indicated that effect predictions based on the concentration addition
      model were always higher than those obtained with the independent action model.
      The observed effect was lower than the effect predicted by the concentration
      addition model for all metal mixtures. Therefore it can be concluded that the
      concentration addition model represents a reasonable worst-case scenario for the
      risk assessment of metal mixtures in terrestrial ecosystems.

PMID- 12051802
TI  - Toxicity and bioaccumulation of fipronil in the nontarget arthropodan fauna
      associated with subalpine mosquito breeding sites.
AB  - In order to examine ecological impact of fipronil use for larval culicine control
      in natural hydrosystems, toxicity and bioaccumulation of this new insecticide
      were analyzed on aquatic species representative of the nontarget arthropodan
      fauna (nonculicine larval Diptera: Chaoboridae, Chironomidae; planktonic
      Crustacea: Cladocera, Copepoda, Ostracoda) associated with target larval mosquito
      populations in the subalpine breeding sites. Standard toxicological bioassays
      using fipronil aqueous solutions from 1 to 2000 nM indicated different
      sensitivity levels among species. Insecticide bioaccumulation analyses, using
      [(14)C]fipronil solutions in simplified laboratory ecosystem, also indicated
      large differences among species. These differences may come from biological
      parameters characteristic of each species. Taking into account these nontarget
      effects of fipronil, a possible strategy of use of this insecticide for
      integrated mosquito control management was proposed, which is based upon
      selective dietary absorption of the insecticide by larval Culicidae.

PMID- 12051803
TI  - Studies of masculinization, detoxification, and oxidative stress responses in
      guppies (Poecilia reticulata) exposed to effluent from a pulp mill.
AB  - Potential masculinization, detoxification, and oxidative stress responses were
      assessed in domesticated female guppies (Poecilia reticulata) exposed for 42 days
      to diluted effluent from a modern Swedish kraft pulp mill or a model androgen.
      Methyltestosterone induced male-like coloration and transformation of the anal
      fin into a gonopodium-like structure. The effluent did not induce any apparent
      changes of the anal fin morphology; however, the exposed guppies became more
      colored than control fish, which could be an androgenic response. A better
      understanding of the physiological mechanisms involved in these responses would
      be required for a full evaluation. Both primary effluent and effluent which had
      undergone activated sludge treatment caused a moderate but significant induction
      of hepatic ethoxyresorufin-O-deethylase (EROD) activity. However, the general
      toxicity of both effluents was low, as mortality was negligible even at 25%
      dilutions. There was a continuous production of offspring in all groups (47-62%
      female fry), except by methyltestosterone-treated females, which did not
      reproduce. There were no indications that either effluent caused oxidative stress
      since hepatic glutathione reductase, glutathione S-transferase and DT-diaphorase
      activities remained unchanged compared with controls.

PMID- 12051804
TI  - Phagocytic response of terrestrial and aquatic invertebrates following in vitro
      exposure to trace elements.
AB  - The potential of the trace elements Ag, As, Cd, Hg, Mo, Ni, Pb, Se, and Zn to
      inhibit the phagocytosis response of extruded coelomocytes of different worm
      species was tested. We used flow cytometry to evaluate the sensitivity of cell
      viability and phagocytic potential for Eisenia fetida, Lumbricus terrestris,
      Aporrectodea turgida, and Tubifex tubifex. Extruded cells were exposed 18 h in
      vitro to concentrations ranging from 10(-9) to 10(-4) M. Mercury was the most
      potent immunotoxic element, with 50% inhibition of phagocytosis occurring at
      concentrations between 10(-7) and 10(-6) M. Cadmium, Cu, Ni, and Zn also showed
      significant immunosuppressive effects with concentrations inducing 50% inhibition
      ranging from 10(-5) to 10(-4) M. Species-specific sensitivity varied by about a
      factor of 10, with no species showing a systematically higher or lower in vitro
      sensitivity across the range of trace elements tested.

PMID- 12051805
TI  - Toxicity of selenomethionine- and seleno-contaminated sediment to the amphipod
      Corophium sp.
AB  - The acute toxicity of four chemical species of selenium to juvenile amphipods
      (Corophium sp.) was assessed in water-only tests. The seleno-amino acid compounds
      seleno-L-methionine and seleno-DL-cystine were found to be more toxic (96-h
      LC(50) values of 1.5 and 12.7 microg Se/L) than the inorganic selenite and
      selenate (96-h NOEC values of 58 and 116 microg Se/L). New marine sediment
      testing procedures were developed using juvenile and adult Corophium sp. Both
      life stages were highly sensitive to seleno-L-methionine-spiked sediment. The
      juveniles were approximately five times more sensitive, with a 10-day LC(50) of
      1.6 microg Se/g (dry weight) compared to 7.6 microg Se/g (dry weight) for the
      adults. Sediment collected from three sites in Lake Macquarie, a marine barrier
      lagoon with elevated concentrations of total selenium, had no effect on the
      survival of adult Corophium over 10 days. The toxicity of seleno-L-methionine to
      other amphipod species occurring in Lake Macquarie was assessed in water-only
      tests, with Paracalliope australis being highly sensitive (96-h LC(50) 2.58
      microg Se/L).

PMID- 12051806
TI  - Inhibitory effects of estrogenic compounds, 4-nonylphenol and genistein, on 7,12
      dimethylbenz[a]anthracene-induced ovarian carcinogenesis in rats.
AB  - The modifying effects of dietary feeding of estrogenic compounds, 4-nonylphenol
      (4-NP) and genistein (GS), on 7,12-dimethylbenz[a]anthracene (DMBA)-induced
      ovarian carcinogenesis were investigated in female Sprague-Dawley rats. We also
      assessed the effects of test compounds on proliferating cell nuclear antigen
      (PCNA) index and the expression of estrogen receptor (ER)-alpha and -beta and
      androgen receptor (AR) in induced neoplasms. Rats were given a single injection
      of DMBA (0.01 ml of 0.5- DMBA suspended in olive oil) into their left ovary to
      induce ovarian neoplasms. They also received the experimental diet containing 25
      to 250 ppm 4-NP or GS for 50 weeks, starting one week after the dosing of DMBA.
      DMBA exposure produced ovarian adenocarcinoma with an incidence of 35% at the end
      of the study (Week 51). Dietary administration of 4-NP or GS caused significant
      reduction in the incidence of ovarian adenocarcinoma: 86% reduction (P=0.0218) by
      feeding of 25 or 250 ppm 4-NP and 25 ppm GS, and 100% reduction (P=0.0042) by
      feeding of 250 ppm GS. The PCNA index in adenocarcinomas was higher than that of
      surface ovarian epithelium. ER-alpha, beta and AR were expressed in a variable
      percentage of moderately and poorly differentiated adenocarcinoma cell nuclei,
      but not in well-differentiated adenocarcinoma cells. These results might suggest
      that dietary feeding of estrogenic compounds either synthetic (4-NP) or natural
      (GS) could act as an inhibitor of DMBA-induced rat ovarian carcinogenesis.

PMID- 12051807
TI  - Regulatory implications of using constructed wetlands to treat selenium-laden
      wastewater.
AB  - The practice of using constructed wetlands to treat selenium-laden wastewater is
      gaining popularity in the United States and elsewhere. However, proponents of
      treatment wetlands often overlook important ecological liabilities and regulatory
      implications when developing new methods and applications. Their research studies
      typically seek to answer a basic performance question--are treatment wetlands
      effective in improving water quality--rather than answering an implicit safety
      question-are they hazardous to wildlife. Nevertheless, wetland owners are
      responsible for both the operational performance of treatment wetlands and the
      health of animals that use them. This is true even if wetlands were not created
      with the intent of providing wildlife habitat; the owner is still legally
      responsible for toxic hazards. If poisoning of fish and wildlife occurs, the
      owner can be prosecuted under a variety of federal and state laws, for example,
      the Migratory Bird Treaty Act and the Endangered Species Act. In considering this
      type of treatment technology it is important to document the selenium content of
      the wastewater, understand how it cycles and accumulates in the environment, and
      evaluate the threat it may pose to fish and wildlife before deciding whether or
      not to proceed with construction. Many of the potential hazards may not be
      obvious to project planners, particularly if there is no expressed intention for
      the wetland to provide wildlife habitat. Ecological risk assessment provides an
      approach to characterizing proposed treatment wetlands with respect to wildlife
      use, selenium contamination, and possible biological impacts. Proper application
      of this approach can reveal potential problems and the associated liabilities,
      and form the basis for selection of an environmentally sound treatment option.

PMID- 12051808
TI  - Differential sensitivity of two green algae, Scenedesmus obliqnus and Chlorella
      pyrenoidosa, to 12 pesticides.
AB  - Growth-inhibiting tests were carried out for 12 pesticides (including 11
      fungicides: fosetyl-aluminum, benomyl, metalaxyl, iprodione, dimetachlone,
      carbendazim, thiophanate-methyl, bismerthiazol, procymidone, zineb,
      chlorothalonil, and the acaricide abamectin) in the green algae Chlorella
      pyrenoidosa and Scenedesmus obliqnus and the differential sensitivities of the
      two green algae to those pesticides were compared. The results indicate that the
      acute toxicity of benomyl to C. pyrenoidosa and S. obliqnus is the highest among
      all of the pesticides tested and is close to that of the photosynthesis
      inhibiting herbicides atrazine, simazine, and chlorotoluron. Meanwhile, algal
      species vary widely in their response to the pesticides. The results demonstrated
      that there was a differential response to various pesticides by the two species
      of algae and that the sensitivity of various species of algae exposed to
      chlorothalonil varied by nearly two orders of magnitude; sensitivity to
      thiophanate-methyl varied by more than one order. Investigations using different
      algal species as test organisms have demonstrated that algae vary greatly in
      their response to chemicals. Differential sensitivity of green species to the
      compounds could induce species shifts within communities.

PMID- 12051809
TI  - Liver phase I and phase II enzymatic induction and genotoxic responses of beta
      naphthoflavone water-exposed sea bass.
AB  - Sea bass were exposed to 0 (control), 0.1, 0.3, 0.9, and 2.7 microM beta
      naphthoflavone (BNF) for 0, 2, 8, and 16 h in order to assess the chronological
      and concentration relationships between BNF phase I and II biotransformation
      responses, such as liver cytochrome P450 (P450) content, ethoxyresorufin-O
      deethylase (EROD), uridine diphosphate-glucuronosyl transferase (UDP-GT), and the
      genotoxic effects, measured either by erythrocytic micronuclei (EMN) or
      erythrocytic nuclear abnormalities (ENA) tests. Liver alanine aminotransferase
      (ALT) activity and liver somatic index (LSI) were also measured. A significant
      liver EROD activity was found at 8 h exposure, respectively, to 0.1, 0.3, 0.9,
      and 2.7 microM BNF. Maximal liver EROD activity increase was observed at 16 h
      exposure to 0.9 microM BNF, whereas the highest liver P450 was reached at 8 h
      exposure to 2.7 microM BNF. Liver UDP-GT activity was significantly increased at
      2 h exposure to 0.1 and 0.3 microM BNF and at 8 h exposure to 0.1, 0.3, and 0.9
      microM BNF, decreasing at 16 h, for every exposure concentration. Significant ENA
      increase was observed at 2h exposure, respectively, to 0.3, 0.9, and 2.7 microM
      BNF. Maximal ENA increase was observed at 16 h exposure to 0.9 microM BNF. The MN
      was significantly increased at 8 and 16 h exposure, respectively, to 2.7 and 0.9
      microM BNF. Liver ALT activity significantly increases at 8 h exposure to 0.1 and
      0.3 microM BNF, whereas liver somatic index was significantly increased from 2 to
      16 h exposure for every BNF concentration. A slight liver EROD activity increase
      with a concomitant lack of liver UDP-GT activity is able to induce significant
      erythrocytic genotoxic effects. Liver UDP-GT high levels are important in sea
      bass BNF detoxification. However, high liver UDP-GT activity is not enough to
      prevent the BNF metabolite genotoxic effects on sea bass erythrocytes when liver
      EROD activity is induced at 2 and 8 h exposure to 0.3 and 0.9 microM BNF. The
      genotoxic effects measured as EMN and ENA suggest that the balance between the
      rates of liver BNF reactive and conjugated metabolites seems to be critical.

PMID- 12051811
TI  - Joint toxicity of linear alkylbenzene sulfonates and pyrene on Folsomia
      fimetaria.
AB  - Surfactants may enhance the biodegradation of hydrophobic substances in soils.
      This has partly been attributed to an increase in the bioavailability, brought
      about by the presence of surfactants. The aim of this study was to examine the
      ecotoxicological effects of the detergent linear alkylbenzene sulfonate (LAS) and
      the polycyclic aromatic hydrocarbon pyrene, alone and in combination, using the
      survival and reproduction of the collembolan Folsomia fimetaria as endpoints. The
      EC(50) and EC(10) were 803 and 161 mg kg(-1) for LAS, and 23 and 15 mg kg(-1) for
      pyrene. If LAS was able to increase the bioavailability of pyrene to springtails,
      it was expected that the combined effect of the two substances would exceed the
      effect found for each of the compounds tested separately. However, the results
      showed no effect of LAS on the toxicity of pyrene in the concentration range
      tested (1-750 mg LAS kg(-1) dry weight). Both the toxic unit concept and the
      isobologram method indicated that an additive approach would be the most useful
      when assessing the risk of these two compounds.

PMID- 12051810
TI  - Beta-naphthoflavone liver EROD and erythrocytic nuclear abnormality induction in
      juvenile Dicentrarchus labrax L.
AB  - Juvenile Dicentrarchus labrax L. (sea bass) was exposed to five different beta
      naphthoflavone (BNF) concentrations-0, 0.1, 0.3, 0.9 and 2.7 microM-for 0, 2, 4,
      6, 8, 16, 24, 48, 72, 144, and 216 h. A battery of biomarkers was investigated,
      such as liver ethoxyresorufin-O-deethylase (EROD), liver cytochrome P450 (P450
      content), liver aminotransferase (ALT activity), liver somatic index (LSI),
      micronuclei (MN), and erythrocytic nuclear abnormality (ENA) frequencies.
      Juvenile D. labrax L. liver EROD induction started at 2 h exposure to 2.7 microM
      BNF and 6 h exposure to 0.1, 0.3, and 0.9 microM BNF, respectively. A significant
      liver EROD decrease was observed between 8 and 16 h for all BNF concentrations,
      followed by a slight increase after 48 h exposure to 0.9 and 2.7 microM BNF and a
      definitive decrease from 72 h exposure onward. Liver P450 content significantly
      increased at 2, 6, and 8 h exposure, respectively, to 2.7 microM, 0.9, 0.3, and
      0.1 microM BNF. However, liver P450 content remained significantly higher than
      that of the control from 72 to 216 h in the sea bass exposed to 2.7 microM BNF.
      Sea bass ENA induction started at 4h exposure to 0.9 and 2.7 microM BNF, and
      significantly increased to 16 and 24 h exposure, whereas for 0.3 microM BNF a
      significant increase started after 8 h exposure. A significant ENA frequency
      increase was still observed at 144 and 216 h exposure to 0.9 and 2.7 microM BNF.
      The micronuclei induction was observed at 4, 6, and 8 h, respectively, after 2.7,
      0.9, and 0.3 microM BNF exposure. However, there was a micronuclei frequency
      decrease for 0.3, 0.9, and 2.7 microM BNF exposure concentrations between 8 and
      16 h, followed by a slight increase after 48, 72, and 144 h exposure,
      respectively, to 2.7, 0.9, and 0.3 microM BNF. Liver somatic index significantly
      increased after 216 h, whereas ALT activity significantly decreased at 144 and
      216 h 2.7 microM BNF exposure.

PMID- 12051813
TI  - Laminin alpha 5 is required for lobar septation and visceral pleural basement
      membrane formation in the developing mouse lung.
AB  - Laminin alpha/beta/gamma heterotrimers are the major noncollagenous components of
      all basement membranes. To date, five alpha, three beta, and three gamma chains
      have been identified. Laminin alpha 5 is expressed early in lung development and
      colocalizes with laminin alpha1. While laminin alpha1 expression in the lung is
      restricted to the embryonic period, laminin alpha 5 expression persists
      throughout embryogenesis and adulthood. Targeted mutation of the mouse laminin
      alpha 5 gene Lama5 causes embryonic lethality at E14-E17 associated with
      exencephaly, syndactyly, placentopathy, and kidney defects, all attributable to
      abnormal basement membranes. In this investigation, lung development in Lama5(-/
      ) mice up to E16.5 was examined. We observed normal lung branching morphogenesis
      and vasculogenesis, but incomplete lobar septation and absence of the visceral
      pleura basement membrane. Preservation of branching morphogenesis was associated
      with ectopic deposition of laminin alpha 4 in the airway basement membrane.
      Perturbation of pleural basement membrane formation and right lung septation
      correlated with absence of laminin alpha 5, which was found to be the only
      laminin alpha chain present in the normal visceral pleura basement membrane. Our
      finding of normal lung branching morphogenesis with abnormal lobar septation
      demonstrates that these processes are not obligatorily linked.

PMID- 12051814
TI  - Membrane-bound neuregulin1 type III actively promotes Schwann cell
      differentiation of multipotent Progenitor cells.
AB  - Many steps of peripheral glia development appear to be regulated by neuregulin1
      (NRG1) signaling but the exact roles of the different NRG1 isoforms in these
      processes remain to be determined. While glial growth factor 2 (GGF2), a NRG1
      type II isoform, is able to induce a satellite glial fate in neural crest stem
      cells, targeted mutations in mice have revealed a prominent role of NRG1 type III
      isoforms in supporting survival of Schwann cells at early developmental stages.
      Here, we investigated the role of NRG1 isoforms in the differentiation of Schwann
      cells from neural crest-derived progenitor cells. In multipotent cells isolated
      from dorsal root ganglia, soluble NRG1 isoforms do not promote Schwann cell
      features, whereas signaling by membrane-associated NRG1 type III induces the
      expression of the Schwann cell markers Oct-6/SCIP and S100 in neighboring cells,
      independent of survival. Thus, axon-bound NRG1 might actively promote both
      Schwann cell survival and differentiation.

PMID- 12051815
TI  - Mnb/Dyrk1A is transiently expressed and asymmetrically segregated in neural
      progenitor cells at the transition to neurogenic divisions.
AB  - The Minibrain (Mnb) gene encodes a new family of protein kinases that is
      evolutionarily conserved from insects to humans. In Drosophila, Mnb is involved
      in postembryonic neurogenesis. In humans, MNB has been mapped within the Down's
      Syndrome (DS) critical region of chromosome 21 and is overexpressed in DS
      embryonic brain. In order to study a possible role of Mnb on the neurogenesis of
      vertebrate brain, we have cloned the chick Mnb orthologue and studied the
      spatiotemporal expression of Mnb in proliferative regions of the nervous system.
      In early embryos, Mnb is expressed before the onset of neurogenesis in the three
      general locations where neuronal precursors are originated: neuroepithelia of the
      neural tube, neural crest, and cranial placodes. Mnb is transiently expressed
      during a single cell cycle of neuroepithelial progenitor (NEP) cells. Mnb
      expression precedes and widely overlaps with the expression of Tis21, an
      antiproliferative gene that has been reported to be expressed in the onset of
      neurogenic divisions of NEP cells. Mnb transcription begins in mitosis, continues
      during G(1), and stops before S-phase. Very interestingly, we have found that Mnb
      mRNA is asymmetrically localized during the mitosis of these cells and inherited
      by one of the sibling cells after division. We propose that Mnb defines a
      transition step between proliferating and neurogenic divisions of NEP cells.

PMID- 12051816
TI  - Zebrafish SPI-1 (PU.1) marks a site of myeloid development independent of
      primitive erythropoiesis: implications for axial patterning.
AB  - The mammalian transcription factor SPI-1 (synonyms: SPI1, PU.1, or Sfpi1) plays a
      critical role in myeloid development. To examine early myeloid commitment in the
      zebrafish embryo, we isolated a gene from zebrafish that is a SPI-1 orthologue on
      the basis of homology and phylogenetic considerations. The zebrafish spi1 (pu1)
      gene was first expressed at 12 h postfertilization in rostral lateral plate
      mesoderm (LPM), anatomically isolated from erythroid development in caudal
      lateral plate mesoderm. Fate-mapping traced rostral LPM cells from the region of
      initial spi1 expression to a myeloid fate. spi1 expression was lost in the
      bloodless mutant cloche, but rostral spi1 expression and myeloid development were
      preserved in the mutant spadetail, despite its complete erythropoietic failure.
      This dissociation of myeloid and erythroid development was further explored in
      studies of embryos overexpressing BMP-4, or chordin, in bmp-deficient swirl and
      snailhouse mutants, and chordin-deficient chordino mutants. These studies
      demonstrate that, in zebrafish, spi1 marks a rostral population of LPM cells
      committed to a myeloid fate anatomically separated from and developmentally
      independent of erythroid commitment in the caudal LPM. Such complete anatomical
      and developmental dissociation of two hematopoietic lineages adds an interesting
      complexity to the understanding of vertebrate hematopoietic development and
      presents significant implications for the mechanisms regulating axial patterning.

PMID- 12051817
TI  - An epithelial precursor is regulated by the ureteric bud and by the renal stroma.
AB  - Kidney epithelia develop from the metanephric mesenchyme after receiving
      inductive signals from the ureteric bud and from the renal stroma. However, it is
      not clear how these signals induce the different types of epithelia that make up
      the nephron. To investigate inductive signaling, we have isolated clusters of
      epithelial progenitors from the metanephric mesenchyme, thereby separating them
      from the renal stroma. When the isolated progenitors were treated with the
      ureteric bud factor LIF, they expressed epithelial proteins (ZO-1, E-cadherin,
      laminin alpha(5)) and produced nephrons (36 glomeruli with 58 tubules),
      indicating that they are the target of inductive signaling from the ureteric bud,
      and that renal stroma is not absolutely required for epithelial development in
      vitro. In fact, stroma-depleted epithelial progenitors produced sevenfold more
      glomeruli than did intact metanephric mesenchyme (5 glomeruli, 127 tubules).
      Conversely, when epithelial progenitors were treated with both LIF and proteins
      secreted from a renal stromal cell line, glomerulogenesis was abolished but
      tubular epithelia were expanded (0 glomeruli, 47 tubules). Hence, by isolating
      epithelial progenitors from the metanephric mesenchyme, we show that they are
      targeted by factors from the ureteric bud and from the renal stroma, and that
      epithelial diversification is stimulated by the ureteric bud and limited by renal
      stroma.

PMID- 12051818
TI  - Localized BMP4-noggin interactions generate the dynamic patterning of noggin
      expression in somites.
AB  - Interactions between BMP4 and its inhibitor, noggin, regulate patterning of
      somites and neural crest. During mesoderm development, noggin mRNA is expressed
      in the intermediate mesoderm. Upon segmentation, it is detected in the lateral
      portion of epithelial somites becoming progressively medialized as they mature.
      In dissociated segments, noggin becomes transiently confined to the dorsomedial
      lip of the dermomyotome. Here, we investigated the factor(s) that control this
      lateral-to-medial shift in transcription of somitic noggin. Inhibition of BMP
      activity in the caudal lateral plate/intermediate mesoderm prevented noggin
      transcription in the lateral somite. Further rostrally (or later in development),
      inhibition of tube-derived BMP, but not of Wnt activity, prevented initial noggin
      expression in the dorsomedial lip of the dermomyotome. Moreover, BMP4 was
      sufficient to trigger initial expression of noggin even in the absence of
      ectoderm and/or neural tube, suggesting a direct action on the dorsomedial
      somite. Thus, the patterns of noggin transcription in somites are directly
      regulated by BMP4 activities emanating first from the mesoderm and later from the
      neural tube. Expression patterns of BMP4 and of type IA BMP receptors are
      spatiotemporally compatible with this lateral-to-medial shift. These results
      highlight the existence in the neural tube-mesoderm complex of a regulatory loop
      by which BMP positively regulates transcription of noggin, which in turn
      represses further ligand activity.

PMID- 12051819
TI  - Control of intercalation is cell-autonomous in the notochord of Ciona
      intestinalis.
AB  - Dishevelled signaling plays a critical role in the control of cell intercalation
      during convergent extension in vertebrates. This study presents evidence that
      Dishevelled serves a similar function in the Ciona notochord. Embryos transgenic
      for mutant Dishevelled fail to elongate their tails, and notochord cells fail to
      intercalate, though notochord cell fates are unaffected. Analysis of mosaic
      transgenics revealed that the effects of mutant Dishevelled on notochord
      intercalation are cell-autonomous in Ciona, though such defects have
      nonautonomous effects in Xenopus. Furthermore, our data indicate that notochord
      cell intercalation in Ciona does not require the progressive signals which
      coordinate cell intercalation in the Xenopus notochord, highlighting an important
      difference in how mediolateral cell intercalation is controlled in the two
      animals. Finally, this study establishes the Ciona embryo as an effective in vivo
      system for the study of the molecular control of morphogenetic cell movements in
      chordates.

PMID- 12051820
TI  - Expression of Patella vulgata orthologs of engrailed and dpp-BMP2/4 in adjacent
      domains during molluscan shell development suggests a conserved compartment
      boundary mechanism.
AB  - The engrailed gene is well known from its role in segmentation and central
      nervous system development in a variety of species. In molluscs, however,
      engrailed is involved in shell formation. So far, it seemed that engrailed had
      been co-opted uniquely for this particular process in molluscs. Here, we show
      that, in the gastropod mollusc Patella vulgata, an engrailed ortholog is
      expressed in the edge of the embryonic shell and in the anlage of the apical
      sensory organ. Surprisingly, a dpp-BMP2/4 ortholog is expressed in cells of the
      ectoderm surrounding, but not overlapping, the engrailed-expressing shell-forming
      cells. It is also expressed in the anlage of the eyes. Earlier it was shown that
      a compartment boundary exists between the cells of the embryonic shell and the
      adjacent ectoderm. We conclude that engrailed and dpp are most likely involved in
      setting up a compartment boundary between these cells, very similar to the
      situation in, for example, the developing wing imaginal disc in Drosophila. We
      suggest that engrailed became involved in shell formation because of its
      ancestral role, which is to set up compartment boundaries between embryonic
      domains.

PMID- 12051822
TI  - A germline-specific splicing generates an extended ovo protein isoform required
      for Drosophila oogenesis.
AB  - Most regulatory genes are employed multiple times to control different processes
      during development. The Drosophila Ovo/Shavenbaby (Svb) transcription factor is
      required both for germline and epidermal differentiation, two roles also found
      for its ortholog m-ovo1 in mice. In Drosophila, these two distinct functions are
      contributed by separate control regions directing the expression of Ovo/Svb in
      the germline (ovo) and soma (svb), respectively. We report here that alternative
      splicing represents an additional level of the regulation of Ovo/Svb functional
      specificity. Characterization of the ovo(D1rv23) mutation revealed that the
      intragenic insertion of a novel retrotransposon, romano, inactivates ovo without
      altering svb. We provide evidence that this insertion disrupts a germline
      specific alternative exon, exon 2b, which encodes a 178-amino-acid internal
      extension (2B). While both isoforms, Ovo+2B and Ovo-2B, accumulate during
      oogenesis, only Ovo+2B is able to fulfill germinal ovo functions. Ovo-2B is
      unable, even when overexpressed, to fully rescue oogenic defects resulting from
      the absence of wild type ovo product. By contrast, either Ovo+2B or Ovo-2B
      germline protein can substitute for Svb in the epidermis. Our results emphasize
      the specific features of splicing in the germline, and reveal its functional
      importance for the control of ovo/svb-dependent ovarian and epidermal
      differentiation.

PMID- 12051823
TI  - Cnidarian and bilaterian promoters can direct GFP expression in transfected
      hydra.
AB  - Complete sexual development is not easily amenable to experimentation in hydra.
      Therefore, the analysis of gene function and gene regulation requires the
      introduction of exogenous DNA in a large number of cells of the hydra polyps and
      the significant expression of reporter constructs in these cells. We present here
      the procedure whereby we coupled DNA injection into the gastric cavity to
      electroporation of the whole animal in order to efficiently transfect hydra
      polyps. We could detect GFP fluorescence in both endodermal and ectodermal cell
      layers of live animals and in epithelial as well as interstitial cell types of
      dissociated hydra. In addition, we could confirm GFP protein expression by
      showing colocalisation between GFP fluorescence and anti-GFP immunofluorescence.
      Finally, when a FLAG epitope was inserted in-frame with the GFP coding sequence,
      GFP fluorescence also colocalised with anti-FLAG immunofluorescence. This GFP
      expression in hydra cells was directed by various promoters, either homologous,
      like the hydra homeobox cnox-2 gene promoter, or heterologous, like the two
      nematode ribosomal protein S5 and L28 gene promoters, and the chicken beta-actin
      gene promoter. This strategy provides new tools for dissecting developmental
      molecular mechanisms in hydra; more specifically, the genetic regulations that
      take place in endodermal cells at the time budding or regeneration is initiated.

PMID- 12051821
TI  - Disruption of testis cords by cyclopamine or forskolin reveals independent
      cellular pathways in testis organogenesis.
AB  - Most studies to date indicate that the formation of testis cords is critical for
      proper Sertoli cell differentiation, inhibition of germ cell meiosis, and
      regulation of Leydig cell differentiation. However, the connections between these
      events are poorly understood. The objective of this study was to dissect the
      molecular and cellular relationships between these events in testis formation. We
      took advantage of the different effects of two hedgehog signaling inhibitors,
      cyclopamine and forskolin, on gonad explant cultures. Both hedgehog inhibitors
      phenocopied the disruptive effect of Dhh(-/-) on formation of testis cords
      without influencing Sertoli cell differentiation. However, they exhibited
      different effects on other cellular events during testis development. Treatment
      with cyclopamine did not affect inhibition of germ cell meiosis and mesonephric
      cell migration but caused defects in Leydig cell differentiation. In contrast,
      forskolin treatment induced germ cell meiosis, inhibited mesonephric cell
      migration, and had no effect on Leydig cell differentiation. By carefully
      contrasting the different effects of these two hedgehog inhibitors, we
      demonstrate that, although formation of testis cords and development of other
      cell types normally take place in a tightly regulated sequence, each of these
      events can occur independent of the others.

PMID- 12051824
TI  - Joint development in the Drosophila leg: cell movements and cell populations.
AB  - Flexible joints separate the rigid sections of the insect leg, allowing them to
      move. In Drosophila, the initial patterning of these joints is apparent in the
      larval imaginal discs from which the adult legs will develop. Here, we describe
      the later patterning and morphogenesis of the joints, which occurs after
      pupariation (AP). In the tibial/tarsal joint, the apodeme insertion site provides
      a fixed marker for the boundary between proximal and distal joint territories
      (the P/D boundary). Cells on either side of this boundary behave differently
      during morphogenesis. Morphogenesis begins with the apical constriction of distal
      joint cells, about 24 h AP. Distal cells then become columnar, causing distal
      tissue nearest the P/D boundary to fold into the leg. In the last stage of joint
      morphogenesis, the proximal joint cells closest to the P/D boundary align and
      elongate to form a "palisade" (a row of columnar cells) over the distal joint
      cells. The proximal and distal joint territories are characterised by the
      differential organisation of cytoskeletal and extracellular matrix proteins, and
      by the differential expression of enhancer trap lines and other gene markers.
      These markers also define a number of more localised territories within the pupal
      joint.

PMID- 12051825
TI  - Directionality of heart looping: effects of Pitx2c misexpression on flectin
      asymmetry and midline structures.
AB  - A critical regulatory laterality gene expressed in the left side of the straight
      heart tube during development is Pitx2, which when mutated in humans underlies
      Rieger's Syndrome. Previously reported results have indicated that, when using
      gain-of-function and loss-of function approaches of the chick cPitx2c isoform,
      this results in randomization of heart looping. To determine whether Pitx2c
      misexpression affects downstream morphogenesis by altering the expression of
      specific proteins in the myocardium during looping, after experimental
      manipulations, we analyzed immunohistochemically for the extracellular matrix
      molecule flectin that normally is expressed predominantly in the left lateral
      plate mesoderm (LPM) and left side of the straight chick heart tube before and
      during looping. We show here that the left-side predominance of flectin is due to
      a delay in the timing of expression in one heart field vs the other. Experimental
      results indicate that misexpression of Pitx2c in the heart fields using antisense
      or retroviral delivery perturbs the normal temporal pattern of flectin expression
      in the left LPM relative to the right: abnormally leftward looping hearts show
      predominate right-sided flectin expression in the dorsal mesocardial regions
      around the foregut ventral midline. Additionally, Pitx2c misexpression affects
      the positioning of the developing foregut to more lateral areas, either on the
      right or left side of the embryonic midline. The position of the heart with
      respect to the embryo midline is defined by the position of the foregut.
      Incubating embryos in the presence of flectin antibody caused randomization of
      heart looping or no looping.

PMID- 12051826
TI  - lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGF beta
      signaling pathway.
AB  - In Caenorhabditis elegans, two well-characterized TGF beta signaling cascades
      have been identified: the Small/Male tail abnormal (Sma/Mab) and Dauer formation
      (Daf) pathways. The Sma/Mab pathway regulates body size morphogenesis and male
      tail development. The ligand of the pathway, dbl-1, transmits its signal through
      two receptor serine threonine kinases, daf-4 and sma-6, which in turn regulate
      the activity of the Smads, sma-2, sma-3, and sma-4. In general, Smads have been
      shown to both positively and negatively regulate the transcriptional activity of
      downstream target genes in various organisms. In C. elegans, however, target
      genes have remained elusive. We have cloned and characterized lon-1, a gene with
      homology to the cysteine-rich secretory protein (CRISP) family of proteins. lon-1
      regulates body size morphogenesis, but does not affect male tail development. lon
      1 is expressed in hypodermal tissues, which is the focus of body size
      determination, similar to sma-2, sma-4, and sma-6. Using genetic methods, we show
      that lon-1 lies downstream of the Sma/Mab signaling cascade and demonstrate that
      lon-1 mRNA levels are up-regulated in sma-6-null mutant animals. This provides
      evidence that lon-1 is negatively regulated by Sma/Mab pathway signaling. Taken
      together, these data identify lon-1 as a novel downstream target gene of the dbl
      1 TGF beta-like signaling pathway.

PMID- 12051827
TI  - Slit antagonizes netrin-1 attractive effects during the migration of inferior
      olivary neurons.
AB  - Inferior olivary neurons (ION) migrate circumferentially around the caudal
      rhombencephalon starting from the alar plate to locate ventrally close to the
      floor-plate, ipsilaterally to their site of proliferation. The floor-plate
      constitutes a source of diffusible factors. Among them, netrin-1 is implied in
      the survival and attraction of migrating ION in vivo and in vitro. We have looked
      for a possible involvement of slit-1/2 during ION migration. We report that: (1)
      slit-1 and slit-2 are coexpressed in the floor-plate of the rhombencephalon
      throughout ION development; (2) robo-2, a slit receptor, is expressed in
      migrating ION, in particular when they reach the vicinity of the floor-plate; (3)
      using in vitro assays in collagen matrix, netrin-1 exerts an attractive effect on
      ION leading processes and nuclei; (4) slit has a weak repulsive effect on ION
      axon outgrowth and no effect on migration by itself, but (5) when combined with
      netrin-1, it antagonizes part of or all of the effects of netrin-1 in a dose
      dependent manner, inhibiting the attraction of axons and the migration of cell
      nuclei. Our results indicate that slit silences the attractive effects of netrin
      1 and could participate in the correct ventral positioning of ION, stopping the
      migration when cell bodies reach the floor-plate.

PMID- 12051828
TI  - Follicle-stimulating hormone induces a gap junction-dependent dynamic change in
      [cAMP] and protein kinase a in mammalian oocytes.
AB  - The second messenger cyclic adenosine 5'monophosphate (cAMP) has been implicated
      in controlling meiotic maturation. To date, there have been no direct
      measurements of cAMP in living mammalian oocytes. Here, we have used the
      fluorescently labelled cAMP-dependent protein kinase A (PKA), FlCRhR, to monitor
      cAMP in mouse oocytes. In cumulus-enclosed oocytes, follicle-stimulating hormone
      (FSH) stimulated an increase in the oocyte [cAMP] that was prevented by using the
      gap junction inhibitor, carbenoxolone. The FSH-induced increase in oocyte [cAMP]
      was suppressed in a time-dependent manner by prior exposure to ATP, while
      epidermal growth factor had no effect on basal or stimulated levels of cAMP.
      Finally, using confocal microscopy, we show that the regulatory and catalytic
      subunits of the microinjected PKA are distributed in a punctate manner with a
      stronger accumulation in the perinuclear region. On an increase in [cAMP], in
      response to phosphodiesterase inhibition or FSH, the catalytic subunit diffused
      throughout the cytoplasm and germinal vesicle, while the regulatory subunit
      remained anchored. These experiments show that increases in cAMP in ovarian
      somatic cells are communicated via gap junctions to the oocyte, where it can lead
      to a redistribution of the catalytic subunit of PKA.

PMID- 12051829
TI  - The single amphioxus Mox gene: insights into the functional evolution of Mox
      genes, somites, and the asymmetry of amphioxus somitogenesis.
AB  - Mox genes are members of the "extended" Hox-cluster group of Antennapedia-like
      homeobox genes. Homologues have been cloned from both invertebrate and vertebrate
      species, and are expressed in mesodermal tissues. In vertebrates, Mox1 and Mox2
      are distinctly expressed during the formation of somites and differentiation of
      their derivatives. Somites are a distinguishing feature uniquely shared by
      cephalochordates and vertebrates. Here, we report the cloning and expression of
      the single amphioxus Mox gene. AmphiMox is expressed in the presomitic mesoderm
      (PSM) during early amphioxus somitogenesis and in nascent somites from the tail
      bud during the late phase. Once a somite is completely formed, AmphiMox is
      rapidly downregulated. We discuss the presence and extent of the PSM in both
      phases of amphioxus somitogenesis. We also propose a scenario for the functional
      evolution of Mox genes within chordates, in which Mox was co-opted for somite
      formation before the cephalochordate-vertebrate split. Novel expression sites
      found in vertebrates after somite formation postdated Mox duplication in the
      vertebrate stem lineage, and may be linked to the increase in complexity of
      vertebrate somites and their derivatives, e.g., the vertebrae. Furthermore,
      AmphiMox expression adds new data into a long-standing debate on the extent of
      the asymmetry of amphioxus somitogenesis.

PMID- 12051830
TI  - Spermatogonia-dependent expression of testicular genes in mice.
AB  - Spermatogenesis is initiated by the interaction of germ cells and somatic cells
      in seminiferous tubules. We used cDNA microarrays and representational difference
      analysis to identify genes that are expressed in the testis of the jsd/jsd mutant
      mouse, which contains only type A spermatogonial germ cells and Sertoli cells,
      but not in the testis of the W/W(v) mutant mouse, where Sertoli cells but few
      germ cells are present. We isolated 20 known genes and 4 novel genes, including 2
      genes encoding lipocalin family members (prostaglandin D synthetase and 24p3) and
      2 tumor suppressors (protein tyrosine phosphatase TD14 and Sui1). All 24 of these
      jsd/jsd-derived genes were highly expressed in the cryptorchid testis as well as
      in the jsd/jsd testis. This indicates that their selective expression is not
      directly caused by the as-yet-uncharacterized jsd gene product, but is rather
      correlated to the cessation of spermatogonial differentiation. In situ
      hybridization analysis and flow cytometric sorting followed by reverse
      transcriptase-PCR revealed that these genes are expressed in both the
      spermatogonial germ cells and the somatic cells in the developing gonads and
      adult testes. As the mRNAs of these jsd/jsd-derived genes were barely detectable
      in the W/W(v) testis, we propose that early spermatogonial germ cells regulate
      the expression of a group of testicular genes.

PMID- 12051832
TI  - The tubulin ancestor, FtsZ, draughtsman, designer and driving force for bacterial
      cytokinesis.
AB  - We discuss in this review the regulation of synthesis and action of FtsZ, its
      structure in relation to tubulin and microtubules, and the mechanism of
      polymerization and disassembly (contraction) of FtsZ rings from a specific
      nucleation site (NS) at mid cell. These topics are considered in the light of
      recent immunocytological studies, high resolution structures of some division
      proteins and results indicating how bacteria may measure their mid cell point.

PMID- 12051831
TI  - A TB-RBP and Ter ATPase complex accompanies specific mRNAs from nuclei through
      the nuclear pores and into intercellular bridges in mouse male germ cells.
AB  - The testis brain RNA-binding protein (TB-RBP) functions as an RNA-binding protein
      in brain and testis, binding to conserved sequence elements present in specific
      mRNAs, such as protamine 1 and 2. We show here by RNA gel shift assays,
      immunoprecipitation, and by a novel in situ hybridization immunohistochemical
      technique that TB-RBP binds to AKAP4 mRNA in male mouse germ cells. AKAP4 is a
      component of the fibrous sheath and functions as a scaffolding protein in the
      sperm flagellum. AKAP4 is encoded by an X-linked gene, is expressed solely in
      postmeiotic (haploid) male germ cells, and is an essential protein in all
      spermatozoa, requiring its transport between spermatids as a protein or mRNA.
      AKAP4 mRNA forms a complex with TB-RBP and the Ter ATPase in nuclei and remains
      associated with these proteins as it exits nuclei into the cytoplasm and as it
      passes through intercellular bridges between spermatids. A similar mRNA-TB-RBP
      Ter ATPase association is seen for protamine 2 mRNA, which is stored in the
      cytoplasm of postmeiotic germ cells about 7 days before translation. In contrast,
      no association is seen with PGK-2 mRNA which is initially transcribed early in
      meiosis with increased transcription in postmeiotic male germ cells. Although PGK
      2 mRNA is subject to translational control, it lacks TB-RBP-binding sequences in
      its mRNA. The AKAP4 or protamine 2 mRNA-protein complexes dissociate in late
      stage male germ cells when the mRNAs are translated. We propose that TB-RBP and
      the Ter ATPase are part of a complex that accompanies specific mRNAs in haploid
      mouse male germ cells in intracellular and intercellular movement. The temporal
      relationship of TB-RBP binding and mRNA inactivation in conjunction with the
      subsequent dissociation of the mRNA-protein complex at the time of mRNA
      translation suggests a role in translational suppression and/or mRNA
      stabilization.

PMID- 12051833
TI  - A biological transporter for the delivery of peptide nucleic acids (PNAs) to the
      nuclear compartment of living cells.
AB  - To facilitate nuclear delivery of biomolecules we describe the synthesis of a
      modular transporter bearing a cellular membrane transport peptide (pAntp) and, as
      a cargo, a 16-mer peptide nucleic acid (PNA) covalently linked to a nuclear
      localisation signal (NLS[SV40-T]). Transport peptide and PNA are connected via N
      terminal activated cysteine to form cleavable disulphide bonds. Internalization
      and subsequent delivery of PNA to the nucleus was verified in living and fixed
      cells by confocal laser scanning microscopy (CLSM) and fluorescence correlation
      spectroscopy (FCS). Double-labelling experiments indicate the cytoplasmic
      cleavage of the two modules and the effective nuclear import of the chromophore
      tagged cargo. A non-degradable linker between transport module and cargo as well
      as a construct without NLS did not enable nuclear PNA import under the described
      experimental conditions. FCS-measurements revealed that most of the PNAs
      delivered into the cytoplasm by the modular transporter are anchored or
      encapsulated, indicating that intracellular transport of these compounds is not
      governed by molecular diffusion. Our results clearly demonstrate efficient
      compartment-directed transport using a synthetic, non-toxic modular transporter
      in living cells.

PMID- 12051834
TI  - Determination of the interface of a large protein complex by transferred cross
      saturation measurements.
AB  - In an earlier paper, it was shown that the cross-saturation method enables us to
      identify the contact residues of large protein complexes in a more rigorous
      manner than is possible using chemical shift perturbation and hydrogen-deuterium
      exchange experiments. However, there are limitations within the determination of
      the contact residues by the cross-saturation method, in that the method is
      difficult to apply to protein complexes with a molecular mass over 150 kDa and/or
      with weak binding, since the resonances originating from the complexes should be
      observed directly in the method. In the present work, to overcome these
      limitations, we carried out the cross-saturation measurements under conditions of
      a fast exchange between free and bound states on the NMR time-scale, and
      determined the contact residues of the complex of the B domain of protein A and
      intact IgG, which has a molecular mass of 164 kDa and shows weak binding.

PMID- 12051835
TI  - Regulation of Saccharomyces cerevisiae FET4 by oxygen and iron.
AB  - Saccharomyces cerevisiae expresses two distinct iron transport systems under
      aerobic and anaerobic conditions. The high affinity transporters, Ftr1p and
      Fet3p, are primarily expressed in oxygenated cultures, whereas anaerobic
      conditions induce the low affinity iron transporter, Fet4p. The oxygen regulation
      of FET4 was found to involve the Rox1p transcriptional repressor. The
      physiological significance of this control by Rox1p is twofold. First, FET4
      repression by Rox1p under oxygenated conditions helps minimize metal toxicity.
      Sensitivity towards cadmium was high in either anaerobically grown wild-type
      yeast or in oxygenated rox1Delta strains, and in both cases cadmium toxicity was
      reversed by FET4 mutations. Secondly, the loss of Rox1p repression under
      anaerobic conditions serves to induce FET4 and facilitate continual accumulation
      of iron. We noted that fet4 mutants accumulate lower levels of iron under
      anaerobic conditions. Regulation of FET4 was examined using FET4-lacZ reporters.
      We found that FET4 contains a complex promoter regulated both by oxygen and iron
      status. The region surrounding approximately -960 to -490 contains two consensus
      Rox1p binding sites and mediates Rox1p, but not iron control of FET4. Sequences
      downstream of -490 harbor a consensus binding site for the iron regulatory factor
      Aft1p that is essential for iron regulation in wild-type strains. In addition, a
      secondary mode of iron regulation becomes evident in strains lacking AFT1. The
      induction by iron limitation in conjunction with low oxygen is more than
      additive, suggesting that these activities are synergistic. Fet4p is not the only
      metal transporter that is negatively regulated by oxygen; we find that Rox1p also
      represses S. cerevisiae SMF3, proposed to function in vacuolar iron transport.
      This oxygen control of iron transporter gene expression is part of an adaptation
      response to changes in the redox state of transition metals.

PMID- 12051836
TI  - X-ray crystal structure of benzoate 1,2-dioxygenase reductase from Acinetobacter
      sp. strain ADP1.
AB  - One of the major processes for aerobic biodegradation of aromatic compounds is
      initiated by Rieske dioxygenases. Benzoate dioxygenase contains a reductase
      component, BenC, that is responsible for the two-electron transfer from NADH via
      FAD and an iron-sulfur cluster to the terminal oxygenase component. Here, we
      present the structure of BenC from Acinetobacter sp. strain ADP1 at 1.5 A
      resolution. BenC contains three domains, each binding a redox cofactor: iron
      sulfur, FAD and NADH, respectively. The [2Fe-2S] domain is similar to that of
      plant ferredoxins, and the FAD and NADH domains are similar to members of the
      ferredoxin:NADPH reductase superfamily. In phthalate dioxygenase reductase, the
      only other Rieske dioxygenase reductase for which a crystal structure is
      available, the ferredoxin-like and flavin binding domains are sequentially
      reversed compared to BenC. The BenC structure shows significant differences in
      the location of the ferredoxin domain relative to the other domains, compared to
      phthalate dioxygenase reductase and other known systems containing these three
      domains. In BenC, the ferredoxin domain interacts with both the flavin and
      NAD(P)H domains. The iron-sulfur center and the flavin are about 9 A apart, which
      allows a fast electron transfer. The BenC structure is the first determined for a
      reductase from the class IB Rieske dioxygenases, whose reductases transfer
      electrons directly to their oxygenase components. Based on sequence similarities,
      a very similar structure was modeled for the class III naphthalene dioxygenase
      reductase, which transfers electrons to an intermediary ferredoxin, rather than
      the oxygenase component.

PMID- 12051837
TI  - Transfer RNA gene-targeted retrotransposition of Dictyostelium TRE5-A into a
      chromosomal UMP synthase gene trap.
AB  - The genome of the eukaryotic microorganism Dictyostelium discoideum hosts a
      family of seven non-long terminal repeat retrotransposons (TREs) that show
      remarkable insertion preferences near tRNA genes. We developed an in vivo assay
      to detect tRNA gene-targeted retrotransposition of endogenous TREs in a reporter
      strain of D. discoideum. A tRNA gene positioned within an artificial intron was
      placed into the D. discoideum UMP synthase gene. This construct was inserted into
      the D. discoideum genome and presented as a landmark for de novo TRE insertions.
      We show that the tRNA gene-tagged UMP synthase gene was frequently disrupted by
      de novo insertions of endogenous TRE5-A copies, thus rendering the resulting
      mutants resistant to 5-fluoroorotic acid selection. Approximately 96% of all
      isolated 5-FOA-resistant clones contained TRE5-A insertions, whereas the
      remaining 4% resulted from transposition-independent mutations. The inserted TRE5
      As showed complex structural variations and were found about 50 bp upstream of
      the reporter tRNA gene, similar to previously analysed genomic copies of TRE5-A.
      No integration by other members of the TRE family was observed. We found that
      only 51% of the de novo insertions were derived from autonomous TRE5-A.1 copies.
      The remaining 49% of new insertions were due to TRE5-A.2 elements, which lack the
      proteins required for reverse transcription and integration, but retain
      functional promoter sequences.

PMID- 12051838
TI  - Binding of a group II intron-encoded reverse transcriptase/maturase to its high
      affinity intron RNA binding site involves sequence-specific recognition and
      autoregulates translation.
AB  - Mobile group II introns encode reverse transcriptases that bind specifically to
      the intron RNAs to promote both intron mobility and RNA splicing (maturase
      activity). Previous studies with the Lactococcus lactis Ll.LtrB intron suggested
      a model in which the intron-encoded protein (LtrA) binds first to a primary high
      affinity binding site in intron subdomain DIVa, an idiosyncratic structure at the
      beginning of the LtrA coding sequence, and then makes additional contacts with
      conserved regions of the intron to fold the RNA into the catalytically active
      structure. Here, we analyzed the DIVa binding site by iterative in vitro
      selection and in vitro mutagenesis. Our results show that LtrA binds to a small
      region at the distal end of DIVa that contains the ribosome-binding site and
      initiation codon of the LtrA open reading frame. The critical elements are in a
      small stem-loop structure emanating from a purine-rich internal loop, with both
      sequence and structure playing a role in LtrA recognition. The ribosome-binding
      site falls squarely within the LtrA-binding region and is sequestered directly by
      the binding of LtrA or by stabilization of the small stem-loop or both. Finally,
      by using LacZ fusions in Escherichia coli, we show that the binding of LtrA to
      DIVa down-regulates translation. This mode of regulation limits accumulation of
      the potentially deleterious intron-encoded protein and may facilitate splicing by
      halting ribosome entry into the intron. The recognition of the DIVa loop-stem
      loop structure accounts, in part, for the intron specificity of group II intron
      maturases and has parallels in template-recognition mechanisms used by other
      reverse transcriptases.

PMID- 12051839
TI  - UTP allosterically regulates transcription by Escherichia coli RNA polymerase
      from the bacteriophage T7 A1 promoter.
AB  - In the case of Escherichia coli RNA polymerase, UTP at elevated concentrations
      suppresses terminated transcript accumulation during multiple-round transcription
      from a DNA construct containing the T7 A1 promoter and T(e) terminator. The step
      that is affected by UTP at elevated concentrations is promoter clearance. In an
      attempt to understand better the mechanism by which UTP regulates this step, we
      analyzed the effect of UTP on the formation of pppApU in the presence of only UTP
      and ATP. At elevated concentrations, UTP is a non-competitive inhibitor with
      respect to ATP in the formation of pppApU. This indicates that the effect of UTP
      on the formation of pppApU is mediated through an allosteric site. Moreover, the
      magnitude of the inhibition of pppApU formation is sufficient to account for the
      decrease in terminated transcript accumulation at elevated UTP concentrations.
      Thus, it appears that UTP modulates terminated transcript accumulation during
      multiple-round transcription from this DNA construct by allosteric regulation of
      promoter clearance at the point of transcription initiation.

PMID- 12051840
TI  - RNase E and polyadenyl polymerase I are involved in maturation of CI RNA, the P4
      phage immunity factor.
AB  - Bacteriophage P4 immunity is controlled by a small stable RNA (CI RNA) that
      derives from the processing of primary transcripts. In previous works, we
      observed that the endonuclease RNase P is required for the maturation of CI RNA
      5'-end; moreover, we found that polynucleotide phosphorylase (PNPase), a 3' to 5'
      RNA-degrading enzyme, is required for efficient 5'-end processing of CI RNA,
      suggesting that 3'-end degradation of the primary transcript might be involved in
      the production of proper RNase P substrates. Here, we demonstrate that another
      Escherichia coli nuclease, RNase E, would appear to be involved in this process.
      We found that transcripts of the P4 immunity region are modified by the post
      transcriptional addition of short poly(A) tails and heteropolymeric tails with
      prevalence of A residues. Most oligoadenylated transcripts encompass the whole cI
      locus and are thus compatible as intermediates in the CI RNA maturation pathway.
      On the contrary, in a polynucleotide phosphorylase (PNPase)-defective host,
      adenylation occurred most frequently within cI, implying that such transcripts
      are targeted for degradation. We did not find polyadenylation in a pcnB mutant,
      suggesting that the pcnB-encoded polyadenyl polymerase I (PAP I) is the only
      enzyme responsible for modification of P4 immunity transcripts. Maturation of CI
      RNA 5'-end in such a mutant was impaired, further supporting the idea that
      processing of the 3'-end of primary transcripts is an important step for
      efficient maturation of CI RNA by RNase P.

PMID- 12051841
TI  - In vivo topography of Rap1p-DNA complex at Saccharomyces cerevisiae TEF2 UAS(RPG)
      during transcriptional regulation.
AB  - We have analyzed in detail the structure of RAP1-UAS(RPG) complexes in
      Saccharomyces cerevisiae cells using multi-hit KMnO(4), UV and micrococcal
      nuclease high-resolution footprinting. Three copies of the Rap1 protein are bound
      to the promoter simultaneously in exponentially growing cells, as shown by
      KMnO(4) multi-hit footprinting analysis, causing extended and diagnostic changes
      in the DNA structure of the region containing the UAS(RPG). Amino acid starvation
      does not cause loss of Rap1p from the complex; however, in vivo UV-footprinting
      reveals the occurrence of structural modifications of the complex. Moreover, low
      resolution micrococcal nuclease digestion shows that the chromatin of the entire
      region is devoid of positioned nucleosomes but is susceptible to changes in
      accessibility to the nuclease upon amino acid starvation. The implications of
      these results for the mechanism of Rap1p action are discussed.

PMID- 12051842
TI  - Identification of four GyrA residues involved in the DNA breakage-reunion
      reaction of DNA gyrase.
AB  - DNA supercoiling by DNA gyrase involves the cleavage of a DNA helix, the passage
      of another helix through the break, and the religation of the first helix. The
      cleavage-religation reaction involves the formation of a 5'-phosphotyrosine
      intermediate with the GyrA subunit of the gyrase (A(2)B(2)) complex. We report
      the characterization of mutations near the active-site tyrosine residue in GyrA
      predicted to affect the cleavage-religation reaction of gyrase. We find that
      mutations at Arg32, Arg47, His78 and His80 inhibit DNA supercoiling and other
      reactions of gyrase. These effects are caused by the involvement of these
      residues in the DNA cleavage reaction; religation is largely unaffected by these
      mutations. We show that these residues cooperate with the active-site tyrosine
      residue on the opposite subunit of the GyrA dimer during the cleavage-religation
      reaction.

PMID- 12051843
TI  - The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a
      proposed two metal-ion mechanism.
AB  - We have examined the role of the DNA gyrase B protein in cleavage and religation
      of DNA using site-directed mutagenesis. Three aspartate residues and a glutamate
      residue: E424, D498, D500 and D502, thought to co-ordinate a magnesium ion, were
      mutated to alanine; in addition, the glutamate residue and one aspartate residue
      were mutated to glutamine and asparagine, respectively. We have shown that these
      residues are important for the cleavage-religation reaction and are likely to be
      involved in magnesium ion co-ordination. On separate mutation of two of these
      aspartate residues to cysteine or histidine, the metal ion preference for the DNA
      relaxation activity of gyrase changed from magnesium to manganese (II). We
      present evidence to support the idea that cleavage of each DNA strand involves
      two or more metal ions, and suggest a scheme for the DNA cleavage chemistry of
      DNA gyrase involving two metal ions.

PMID- 12051844
TI  - Functional studies of potential intrastrand triplex elements in the Escherichia
      coli genome.
AB  - We previously used a pattern recognition program for nucleic acids to detect
      sequences with the potential to form intrastrand triplexes. Potential intrastrand
      triplex (PIT) element families were found in Escherichia coli, Synechocystis sp.
      and Haemophilus influenza. We were particularly intrigued with the family found
      in E. coli, which contained 25 dispersed copies of a particular PIT sequence
      corresponding to the purine triplex motif. E. coli PIT elements appear to occur
      exclusively in non-coding regions. We now report biochemical experiments testing
      the interaction of E. coli PIT elements with polymerases and single-stranded DNA
      binding protein (SSB). The elements were also tested in genetic experiments as
      promoters, transcription terminators, or replication pause sites in E. coli. We
      show that PIT elements display provocative characteristics in certain biochemical
      assays. When appropriately oriented, the elements block elongation by Taq DNA
      polymerase at 72 degrees C, but not elongation by T7 DNA polymerase at 37 degrees
      C. The G-rich strand of the E. coli PIT sequence folds into a form with reduced
      affinity for SSB. On the other hand, in vivo studies did not detect replication
      delays for conjugal transfer of episomes containing PIT elements. These sequences
      were shown not to act as promoters, but the presence of PIT elements in RNA
      leaders upstream of a coding region could strongly influence expression of the
      downstream gene. These effects were shown to be post-transcriptional and were
      solely dependent on the Watson-Crick stem-loop structure within the PIT element.
      Thus, although PIT element DNA displays unusual biochemical properties, it
      remains unknown how these elements arose, and why they persist in the E. coli
      genome.

PMID- 12051845
TI  - Communications between catalytic sites in the protein-DNA synapse by the SfiI
      endonuclease.
AB  - The SfiI endonuclease is a tetrameric protein with two DNA-binding clefts. It has
      to bind two copies of its recognition sequence, one at each cleft, before it
      cleaves DNA. While SfiI binds cooperatively to two cognate sites, it binds only
      one non-cognate DNA molecule at a time and the resultant complex is precluded
      from binding cognate DNA at the vacant cleft. To examine the communications
      between separate binding sites in a protein that synapses two segments of DNA,
      SfiI was tested with oligonucleotide duplexes containing its recognition sequence
      but with either R(p) or S(p) phosphorothioate linkages at the scissile bonds.
      Though SfiI has low activity on the R(p) and none against the S(p)
      diastereoisomer, it bound these duplexes in the same cooperative manner as
      oxyester duplexes, though with a reduced affinity for the S(p) derivative. It
      also formed complexes with one phosphorothioate-duplex and one oxyester-duplex
      but, when Mg(2+) was added to the hybrid complexes, the phosphorothioate moiety
      at one DNA-binding cleft prevented the enzyme from cleaving the oxyester duplex
      at the other cleft. SfiI is thus restrained from catalytic action until it
      recognises the correct nucleotide sequence at two DNA loci and the correct
      phosphodiester functions at both loci.

PMID- 12051846
TI  - High-throughput, cloning-independent protein library construction by combining
      single-molecule DNA amplification with in vitro expression.
AB  - A novel, cloning-independent strategy for construction of protein libraries has
      been developed and demonstrated experimentally. A pool of genes is prepared and
      thereafter extensively diluted to give one molecule of DNA per well. Each
      individual molecule is amplified separately by polymerase chain reaction (single
      molecule PCR) yielding a PCR library. Subsequently, the PCR library is directly
      transformed into a protein library by means of in vitro coupled
      transcription/translation. Amounts of DNA produced by the single-molecule PCR
      were equal and uniformity of amounts of successively in vitro synthesized
      proteins, which were critical for quantitative comparison among clones in the
      library, was better than that of the classical in vivo expression system. Here,
      we describe a library of anti-human serum albumin single-chain antibodies (anti
      HSA-scFv) originating from a monoclonal anti-HSA-scFv which was constructed and
      screened in order to demonstrate its real practicability. Application of the
      strategy described for high-throughput generation and screening of protein
      libraries is discussed.

PMID- 12051847
TI  - Antibody evolution from the centre to the periphery: applied to a human antibody
      fragment recognising the tumour-associated antigen mucin-1.
AB  - Mucin-1 has proven to be a suitable target for antibody-based diagnosis and
      therapy of certain tumours, but no appropriate human antibody or antibody
      fragment displaying slow dissociation rate kinetics against this target is
      available. Since a rapid dissociation character prevents an antibody fragment
      from remaining at the site of the antigen, this fact may prevent the successful
      application of a human mucin-1 specific antibody in diagnosis and therapy. We
      have now used iterative antibody libraries to evolve a human antibody fragment
      originally obtained from a naive antibody library. A strategy was devised whereby
      molecular variants displaying slow dissociation kinetics against the repetitive
      mucin-1 tumour-associated antigen can be selected in vitro. The evolved clones,
      that allowed for a reduced dissociation from the tumour antigen, carried
      substitutions in the outer parts of the binding site. This demonstrated the
      ability of this in vitro evolution technique to mimic the process whereby
      antibodies evolve in vivo. We have thus devised a strategy through which
      molecular variants displaying slow dissociation from a repetitive target like the
      mucin-1 tumour-associated antigen can be obtained in vitro. These or related
      molecules obtained by this approach will serve as a starting point for the
      development of fully human antibodies for use in mucin-1 specific tumour therapy
      of diagnosis.

PMID- 12051848
TI  - Brownian dynamics simulations of the recognition of the scorpion toxin P05 with
      the small-conductance calcium-activated potassium channels.
AB  - The recognition of the scorpion toxin P05 and the small-conductance, calcium
      activated potassium (SK) channels, rsk1, rsk2, and rsk3, has been studied by
      means of the Brownian dynamics (BD) method. All of the 25 available structures of
      P05 in the RCSB Protein Data Bank determined by NMR were considered during the
      simulation, which indicated that the conformation of P05 affects both the
      recognition and binding between the two proteins significantly. Comparing the top
      four high-frequency structures of P05 binding to the SK channels, we found that
      the rsk2 channel, with high frequencies and lowest electrostatic interaction
      energies (E (int)(ES)), is the most favorable for P05 binding, while rsk3 is
      intermediate, and rsk1 is the least favorable. Among the 25 structures of P05,
      the 13th structure docks into the binding site of the rsk2 channel with the
      highest probability and most favorable electrostatic interactions. From the P05
      rsk2 channel binding model, we identified the residues critical for the
      recognition of these two proteins through triplet contact analyses. P05 locates
      around the extracellular mouth of the SK channels and contacts the SK channels
      using its alpha-helix rather than beta-sheets. The critical triplet contacts for
      recognition between P05 and the rsk2 channel are Arg6 (P05)-Asp364 (SK), Arg7
      (P05)-Asn368 (SK), and Arg13 (P05)-Asp341 (SK). The structure of the P05-rsk2
      complex with the most favorable electrostatic interaction energy was further
      refined by molecular mechanics, showing that six hydrogen bonding interactions
      exist between P05 and the rsk2 channel: one hydrogen bond is formed between Arg6
      (P05) and Asp364(D) (rsk2); Arg7 (P05) forms three hydrogen bonds with Asp341(B)
      (rsk2)) and Asp364(C) (rsk2); two hydrogen bonds are formed by Arg13 (P05) with
      Asp341(A) (rsk2) and Asp364(B) (rsk2). The simulation results are in good
      agreement with the previous molecular biological experiments and can explain the
      binding phenomena between P05 and SK channels at the level of molecular
      structure. The consistency between the results of the BD simulations and the
      experimental data indicated that our 3D model of the P05-rsk2 channel complex is
      reasonable and can be employed in further biological studies, such as rational
      design of the novel therapeutic agents blocking the small-conductance, calcium
      activated and apamin-sensitive potassium channels, and for mutagenesis studies in
      both toxins and SK channels. In particular, both the BD simulations and the
      molecular mechanics refinements indicate that residue Asp364 of the rsk2 channel
      is critical for its recognition and binding functionality towards P05. This
      phenomenon has not been appreciated in the previous mutagenesis experiments,
      indicating that this might be a new clue for further functional study of SK
      channels.

PMID- 12051849
TI  - Knowledge-based design of reagentless fluorescent biosensors from recombinant
      antibodies.
AB  - The possibility of obtaining from any antibody a fluorescent conjugate which
      responds to the binding of the antigen by a variation of its fluorescence, would
      be of great interest in the analytical sciences and for the construction of
      protein chips. This possibility was explored with antibody mAbD1.3 directed
      against hen egg white lysozyme. Rules of design were developed to identify the
      residues of the antibody to which a fluorophore could be chemically coupled,
      after changing them to cysteine by mutagenesis. These rules were based on: the
      target residue belonging to a topological neighbourhood of the antigen in the
      structure of the complex between antibody and antigen; its absence of functional
      importance for the interaction with the antigen; and its solvent accessibility in
      the structure of the free antibody. Seventeen conjugates between the single-chain
      variable fragment scFv of mAbD1.3 and an environment-sensitive fluorophore were
      constructed. For six of the ten residues which fully satisfied the design rules,
      the relative variation of the fluorescence intensity between the free and bound
      states of the conjugate was comprised between 12 and 75% (in non-optimal buffer),
      and the affinity of the conjugate for lysozyme remained unchanged relative to the
      parental scFv. In contrast, such results were true for only one of the seven
      residues which failed to satisfy one of the rules and were used as controls. One
      of the conjugates was studied in more detail. Its fluorescence increased
      proportionally to the concentration of lysozyme in a nanomolar range, up to 90%
      in a defined buffer, and 40% in serum. This increase was specific for hen egg
      lysozyme and it was not observed with a closely related protein, turkey egg
      lysozyme. The residues which gave operational conjugates (six in V(L) and one in
      V(H)), were located in the immediate vicinity of residues which are functionally
      important, along the sequence of FvD1.3. The results suggest rules of design for
      constructing antigen-sensitive fluorescent conjugates from any antibody, in the
      absence of structural data.

PMID- 12051850
TI  - Crystal structures and structural comparison of Thermoactinomyces vulgaris R-47
      alpha-amylase 1 (TVAI) at 1.6 A resolution and alpha-amylase 2 (TVAII) at 2.3 A
      resolution.
AB  - The X-ray crystal structures of Thermoactinomyces vulgaris R-47 alpha-amylase 1
      (TVAI) and alpha-amylase 2 (TVAII) have been determined at 1.6 A and 2.3 A
      resolution, respectively. The structures of TVAI and TVAII have been refined, R
      factor of 0.182 (R(free)=0.206) and 0.179 (0.224), respectively, with good
      chemical geometries. Both TVAI and TVAII have four domains, N, A, B and C, and
      all very similar in structure. However, there are some differences in the
      structures between them. Domain N of TVAI interacts strongly with domains A and
      B, giving a spherical shape structure to the enzyme, while domain N of TVAII is
      isolated from the other domains, which leads to the formation of a dimer. TVAI
      has three bound Ca ions, whereas TVAII has only one. TVAI has eight extra loops
      compared to TVAII, while TVAII has two extra loops compared to TVAI. TVAI can
      hydrolyze substrates more efficiently than TVAII with a high molecular mass such
      as starch, while TVAII is much more active against cyclodextrins than TVAI and
      other alpha-amylases. A structural comparison of the active sites has clearly
      revealed this difference in substrate specificity.

PMID- 12051851
TI  - Hypothesis: a phospholipid translocase couples lateral and transverse bilayer
      asymmetries in dividing bacteria.
AB  - Cell division in bacteria such as Escherichia coli entails changes in the radii
      of curvature of the invaginating cytoplasmic membrane which culminate in
      rearrangements of its monolayers. Division therefore risks perturbing transverse
      and lateral asymmetries and compromising membrane integrity. This leads us to
      propose that a strong selective pressure exists for a phospholipid translocator
      that would transfer phospholipids across the cytoplasmic membrane so as to both
      demarcate the division site and mediate lipid composition during division. This
      translocase has an affinity for phospholipids with small headgroups and
      unsaturated acyl chains which it translocates so as to (1) generate changes in
      the radius of curvature, (2) facilitate septum formation, (3) minimise bilayer
      disruption during fusion and (4) prevent septum formation at old or inappropriate
      division sites. We discuss briefly possible candidates for this translocase
      including ABC transporters and proteins localised to the division site.

PMID- 12051852
TI  - Crystal structure of the alcohol dehydrogenase from the hyperthermophilic
      archaeon Sulfolobus solfataricus at 1.85 A resolution.
AB  - The crystal structure of a medium-chain NAD(H)-dependent alcohol dehydrogenase
      (ADH) from an archaeon has been solved by multiwavelength anomalous diffraction,
      using a selenomethionine-substituted enzyme. The protein (SsADH), extracted from
      the hyperthermophilic organism Sulfolobus solfataricus, is a homo-tetramer with a
      crystallographic 222 symmetry. Despite the low level of sequence identity, the
      overall fold of the monomer is similar to that of the other homologous ADHs of
      known structure. However, a significant difference is the orientation of the
      catalytic domain relative to the coenzyme-binding domain that results in a larger
      interdomain cleft. At the bottom of this cleft, the catalytic zinc ion is
      coordinated tetrahedrally and lacks the zinc-bound water molecule that is usually
      found in ADH apoform structures. The fourth coordination position is indeed
      occupied by a Glu residue, as found in bacterial tetrameric ADHs. Other
      differences are found in the architecture of the substrate pocket whose entrance
      is more restricted than in other ADHs. SsADH is the first tetrameric ADH X-ray
      structure containing a second zinc ion playing a structural role. This latter
      metal ion shows a peculiar coordination, with a glutamic acid residue replacing
      one of the four cysteine ligands that are highly conserved throughout the
      structural zinc-containing dimeric ADHs.

PMID- 12051853
TI  - Insulin at pH 2: structural analysis of the conditions promoting insulin fibre
      formation.
AB  - When insulin solutions are subjected to acid, heat and agitation, the normal
      pattern of insulin assembly (dimers-->tetramers-->hexamers) is disrupted; the
      molecule undergoes conformational changes allowing it to follow an alternative
      aggregation pathway (via a monomeric species) leading to the formation of
      insoluble amyloid fibres. To investigate the effect of acid pH on the
      conformation and aggregation state of the protein, the crystal structure of human
      insulin at pH 2.1 has been determined to 1.6 A resolution. The structure reveals
      that the native fold is maintained at low pH, and that the molecule is still
      capable of forming dimers similar to those found in hexameric insulin structures
      at higher pH. Sulphate ions are incorporated into the molecule and the crystal
      lattice where they neutralise positive charges on the protein, stabilising its
      structure and facilitating crystallisation. The sulphate interactions are
      associated with local deformations in the protein, which may indicate that the
      structure is more plastic at low pH. Transmission electron microscopy analysis of
      insulin fibres reveals that the appearance of the fibres is greatly influenced by
      the type of acid employed. Sulphuric acid produces distinctive highly bunched,
      truncated fibres, suggesting that the sulphate ions have a sophisticated role to
      play in fibre formation, rather as they do in the crystal structure. Analytical
      ultracentrifugation studies show that in the absence of heating, insulin is
      predominantly dimeric in mineral acids, whereas in acetic acid the equilibrium is
      shifted towards the monomer. Hence, the effect of acid on the aggregation state
      of insulin is also complex. These results suggest that acid conditions increase
      the susceptibility of the molecule to conformational change and dissociation, and
      enhance the rate of fibrillation by providing a charged environment in which the
      attractive forces between the protein molecules is increased.

PMID- 12051854
TI  - Crystal structure of beta1,4-galactosyltransferase complex with UDP-Gal reveals
      an oligosaccharide acceptor binding site.
AB  - The crystal structure of the catalytic domain of bovine beta1,4
      galactosyltransferase (Gal-T1) co-crystallized with UDP-Gal and MnCl(2) has been
      solved at 2.8 A resolution. The structure not only identifies galactose, the
      donor sugar binding site in Gal-T1, but also reveals an oligosaccharide acceptor
      binding site. The galactose moiety of UDP-Gal is found deep inside the catalytic
      pocket, interacting with Asp252, Gly292, Gly315, Glu317 and Asp318 residues.
      Compared to the native crystal structure reported earlier, the present UDP-Gal
      bound structure exhibits a large conformational change in residues 345-365 and a
      change in the side-chain orientation of Trp314. Thus, the binding of UDP-Gal
      induces a conformational change in Gal-T1, which not only creates the acceptor
      binding pocket for N-acetylglucosamine (GlcNAc) but also establishes the binding
      site for an extended sugar acceptor. The presence of a binding site that
      accommodates an extended sugar offers an explanation for the observation that an
      oligosaccharide with GlcNAc at the non-reducing end serves as a better acceptor
      than the monosaccharide, GlcNAc. Modeling studies using oligosaccharide acceptors
      indicate that a pentasaccharide, such as N-glycans with GlcNAc at their non
      reducing ends, fits the site best. A sequence comparison of the human Gal-T
      family members indicates that although the binding site for the GlcNAc residue is
      highly conserved, the site that binds the extended sugar exhibits large
      variations. This is an indication that different Gal-T family members prefer
      different types of glycan acceptors with GlcNAc at their non-reducing ends.

PMID- 12051855
TI  - The crystal structure of Trichomonas vaginalis ferredoxin provides insight into
      metronidazole activation.
AB  - Crystallographic studies revealing the three-dimensional structure of the
      oxidized form of the [2Fe-2S] ferredoxin from Trichomonas vaginalis (TvFd) are
      presented. TvFd, a member of the hydrogenosomal class of ferredoxins, possesses a
      unique combination of redox and spectroscopic properties, and is believed to be
      the biological molecule that activates the drug metronidazole reductively in the
      treatment of trichomoniasis. It is the first hydrogenosomal ferredoxin to have
      its structure determined. The structure of TvFd reveals a monomeric, 93 residue
      protein with a fold similar to that of other known [2Fe-2S] ferredoxins. It
      contains nine hydrogen bonds to the sulfur atoms of the cluster, which is more
      than the number predicted on the basis of the spectroscopic data. The TvFd
      structure contains a large dipole moment like adrenodoxin, and appears to have a
      similar interaction domain. Our analysis demonstrates that TvFd has a unique
      cavity near the iron-sulfur cluster that exposes one of the inorganic sulfur
      atoms of the cluster to solvent. This cavity is not seen in any other [2Fe-2S]
      ferredoxin with known structure, and is hypothesized to be responsible for the
      high rate of metronidazole reduction by TvFd.

PMID- 12051856
TI  - Conformational stability of dimeric and monomeric forms of the C-terminal domain
      of human immunodeficiency virus-1 capsid protein.
AB  - The unfolding equilibrium of the C-terminal domain of human immunodeficiency
      virus-1 (HIV-1) capsid protein has been analyzed by circular dichroism and
      fluorescence spectroscopy. The results for the dimeric, natural domain are
      consistent with a three-state model (N(2)<-->2I<-->2U). The dimer (N(2))
      dissociates and partially unfolds in a coupled cooperative process, into a
      monomeric intermediate (I) of very low conformational stability. This
      intermediate, which is the only significantly populated form at low (1 microM)
      protein concentrations, fully preserves the secondary structure but has lost part
      of the tertiary (intramonomer) interactions found in the dimer. In a second
      transition, the intermediate cooperatively unfolds into denatured monomer (U).
      The latter process is the equivalent of a two-state unfolding transition observed
      for a monomeric domain in which Trp184 at the dimer interface had been truncated
      to Ala. A highly conserved, disulfide-bonded cysteine, but not the disulfide bond
      itself, and three conserved residues within the major homology region of the
      retroviral capsid are important for the conformational stability of the monomer.
      All these residues are involved also in the association process, despite being
      located far away from the dimerization interface. It is proposed that
      dimerization of the C-terminal domain of the HIV-1 capsid protein involves
      induced-fit recognition, and the conformational reorganization also improves
      substantially the low intrinsic stability of each monomeric half.

PMID- 12051858
TI  - Folding in vitro of light-harvesting chlorophyll a/b protein is coupled with
      pigment binding.
AB  - The major light-harvesting chlorophyll a/b protein (LHCIIb) of the plant
      photosynthetic apparatus is able to self-organise in vitro. When the recombinant
      apoprotein, Lhcb1, is solubilised in the denaturing detergent sodium (or lithium)
      dodecylsulfate (SDS or LDS) and then mixed with chlorophylls and carotenoids
      under renaturing conditions, structurally authentic LHCIIb forms. Assembly of
      functional LHCIIb, as indicated by the establishment of energy transfer between
      complex-bound chlorophyll molecules, occurs in two apparent kinetic steps with
      time constants of 10 to 30 seconds and 50 to 300 seconds, depending on the
      reaction conditions. Here, we use circular dichroism (CD) in the far-UV range to
      monitor the folding of the LHCIIb apoprotein as it is complexed with pigments.
      The alpha-helix content in the protein's secondary structure increases in two
      apparent kinetic steps with time constants similar to those observed for the
      establishment of chlorophyll energy transfer. When the carotenoid concentration
      in the reaction mixture is reduced, the time constants of alpha-helix formation
      increase, as do those for the appearance of chlorophyll energy transfer. This
      indicates that both processes, pigment assembly and secondary structure
      formation, are tightly coupled. A substantial amount of alpha-helix is present in
      dodecylsulfate-solubilised LHCIIb apoprotein and appears to be distributed among
      various protein domains.

PMID- 12051857
TI  - Interaction of Kazal-type inhibitor domains with serine proteinases: biochemical
      and structural studies.
AB  - The interaction of domains of the Kazal-type inhibitor protein dipetalin with the
      serine proteinases thrombin and trypsin is studied. The functional studies of the
      recombinantly expressed domains (Dip-I+II, Dip-I and Dip-II) allow the dissection
      of the thrombin inhibitory properties and the identification of Dip-I as a key
      contributor to thrombin/dipetalin complex stability and its inhibitory potency.
      Furthermore, Dip-I, but not Dip-II, forms a complex with trypsin resulting in an
      inhibition of the trypsin activity directed towards protein substrates. The high
      resolution NMR structure of the Dip-I domain is determined using multi
      dimensional heteronuclear NMR spectroscopy. Dip-I exhibits the canonical Kazal
      type fold with a central alpha-helix and a short two-stranded antiparallel beta
      sheet. Molecular regions essential for inhibitor complex formation with thrombin
      and trypsin are identified. A comparison with molecular complexes of other Kazal
      type thrombin and trypsin inhibitors by molecular modeling shows that the N
      terminal segment of Dip-I fulfills the structural prerequisites for inhibitory
      interactions with either proteinase and explains the capacity of this single
      Kazal-type domain to interact with different proteinases.

PMID- 12051859
TI  - Characterization of a high-affinity complex between the bacterial outer membrane
      protein FhuA and the phage T5 protein pb5.
AB  - Binding of bacteriophage T5 to Escherichia coli cells is mediated by specific
      interactions between the receptor-binding protein pb5 (67.8 kDa) and the outer
      membrane iron-transporter FhuA. A histidine-tagged form of pb5 was overproduced
      and purified. Isolated pb5 is monomeric and organized mostly as beta-sheets
      (51%). pb5 functionality was attested in vivo by its ability to impair infection
      of E. coli cells by phage T5 and Phi80, and to prevent growth of bacteria on iron
      ferrichrome as unique iron source. pb5 was functional in vitro, since addition of
      an equimolar concentration of pb5 to purified FhuA prevented DNA release from
      phage T5. However, pb5 alone was not sufficient for the conversion of FhuA into
      an open channel. Direct interaction of pb5 with FhuA was demonstrated by
      isolating a pb5/FhuA complex using size-exclusion chromatography. The
      stoichiometry, 1 mol of pb5/1 mol of FhuA, was deduced from its molecular mass,
      established by analytical ultracentrifugation after determination of the amount
      of bound detergent. SDS-PAGE and differential scanning calorimetry experiments
      highlighted the great stability of the complex: (i) it was not dissociated by 2%
      SDS even when the temperature was raised to 70 degrees C; (ii) thermal
      denaturation of the complex occurred at 85 degrees C, while pb5 and FhuA were
      denatured at 45 degrees C and 74 degrees C, respectively. The stability of the
      complex renders it suitable for high-resolution structural studies, allowing
      future analysis of conformational changes into both FhuA and pb5 upon adsorption
      of the virus to its host.

PMID- 12051860
TI  - pH-dependent stability and folding kinetics of a protein with an unusual alpha
      beta topology: the C-terminal domain of the ribosomal protein L9.
AB  - The folding kinetics and thermodynamics of the isolated C-terminal domain of the
      ribosomal protein L9 (CTL9) have been studied as a function of pH. CTL9 is an
      alpha-beta protein that contains a single beta-sheet with an unusual mixed
      parallel, anti-parallel topology. The folding is fully reversible and two-state
      over the entire pH range. Stopped-flow fluorescence and CD experiments yield the
      same folding rate, and the chevron plots have the characteristic V-shape expected
      for two-state folding. The values of DeltaG*(H2O) and the m value calculated from
      the kinetic experiments are in excellent agreement with the equilibrium
      measurements. The extrapolated initial amplitudes of both the stopped-flow
      fluorescence and CD measurements show that there is no detectable burst phase
      intermediate. The domain contains three histidine residues, two of which are
      largely buried in the native state. They do not participate in salt-bridges or
      take part in a hydrogen bonded network. NMR measurements reveal that the buried
      histidine residues have significantly perturbed pK(a) values in the native state.
      The equilibrium stability and the folding rate are found to be strongly dependent
      upon their ionization state. There is a linear relationship between the log of
      the folding rate and DeltaG* (H2O) . The protein is much more stable and folds
      noticeably faster at pH values above the native state pK(a) values. DeltaG*(H2O)
      of unfolding increases from 2.90 kcal mol(-1) at pH 5.0 to 6.40 kcal mol(-1) at
      pH 8.0 while the folding rate increases from 0.60 to 18.7 s(-1). Tanford linkage
      analysis revealed that the interactions involving the two histidine residues are
      largely developed in the transition state. The results are compared to other
      studies of the pH-dependence of folding.

PMID- 12051861
TI  - The C-terminal extension of the small GTPase Ran is essential for defining the
      GDP-bound form.
AB  - The small GTPase Ran controls cellular processes by interacting with members of
      the importin beta family that bind specifically to the GTP-bound form of Ran, and
      this regulates the interaction between importin beta-like proteins and cellular
      factors. The structures of RanGDP and RanGTP are markedly different, and major
      structural changes are found in the switch I and switch II regions and in the C
      terminal extension of Ran. Here, we show that a deletion mutant of Ran, lacking
      the entire C-terminal extension, termed Ran Core, can bind to importin beta in
      its GDP-bound form with high affinity. The ability of Ran CoreGDP to dissociate
      cargo from importin beta results in an import block in digitonin-permeabilized
      cells and leads to microtubule aster formation in mitotic Xenopus egg extract. As
      for importin beta, also transportin, importin 7 and exportin-t can no longer
      discriminate efficiently between the two nucleotide-bound forms of Ran Core. In
      contrast, a significant reduction in affinity of the RanGDP-binding protein NTF2
      for Ran CoreGDP is observed, indicating that the switch regions have changed
      conformation in the Ran Core mutant. Our results demonstrate that the C terminus
      of Ran is a major determinant of the state of Ran, and that removal of this
      allows the GDP-bound form to adopt a GTP-like conformation, thereby creating a
      constitutively active protein.

PMID- 12051862
TI  - Enzyme function less conserved than anticipated.
AB  - The level of sequence similarity that implies similarity in protein structure is
      well established. Recently, many groups proposed thresholds for similarity in
      sequence implying similarity in enzymatic function. All previous results suggest
      the strong conservation of enzymatic function above levels of 50% pairwise
      sequence identity. Here, I argue that all groups substantially overestimated the
      conservation of enzyme function because their data sets were either too biased,
      or too small. An unbiased analysis suggested that less than 30% of the pair
      fragments above 50% sequence identity have entirely identical EC numbers. Another
      surprising finding was that even BLAST E-values below 10(-50) did not suffice to
      automatically transfer enzyme function without errors. As expected, most
      misclassifications originated from similarities in relatively short regions
      and/or from transferring annotations for different domains. Both problems cannot
      be corrected easily by adjusting the thresholds for automatic transfer of genome
      annotations. A score relating sequence identity to alignment length (distance
      from HSSP-threshold) outperformed statistical BLAST scores for high sequence
      similarity. In particular, the distance score allowed error-free transfer of
      enzyme function for the 10% most similar enzyme pairs. The results illustrated
      how difficult it is to assess the conservation of protein function and to
      guarantee error-free genome annotations, in general: sets with millions of pair
      comparisons might not suffice to arrive at statistically significant conclusions.
      In practice, the revised detailed estimates for the sequence conservation of
      enzyme function may provide important benchmarks for everyday sequence analysis
      and for more cautious automatic genome annotations.

PMID- 12051864
TI  - Prophylactic oophorectomy comes of age.

PMID- 12051865
TI  - Peritoneal lavage cytology: an assessment of its value during prophylactic
      oophorectomy.
AB  - OBJECTIVE: Prophylactic oophorectomy (PO) is an accepted treatment strategy for
      women who are at high risk for the development of ovarian carcinoma, particularly
      women who are BRCA mutation-positive. This study sought to assess the utility of
      peritoneal lavage cytology at the time of PO in detecting occult malignancy in
      this group of patients. METHODS: Thirty-five high-risk women, who were not
      suspected of having any malignancy or ovarian mass, underwent peritoneal lavage
      at the time of PO. Thirty-one of the thirty-five women had undergone BRCA
      mutation analysis (BRCA1+, 18; BRCA2+, 10; BRCA-, 3). Intensive histopathologic
      examination was used in all 35 cases to identify occult carcinoma. Lavage
      specimens were reviewed for the presence of malignant cells and endosalpingiosis.
      The cytologic review was conducted without knowledge of either the
      histopathologic or BRCA results. RESULTS: In 32 of the 35 lavage specimens no
      malignancy was detected. In the remaining three cases malignant cells were
      detected; in two of these cases histopathologic examination confirmed an
      ovarian/tubal occult carcinoma. Two of these women were BRCA1 mutation positive.
      Endosalpingiosis was detected in the peritoneal lavage specimens of 7 of the 32
      cases showing no evidence of malignancy. All of these 7 women were BRCA mutation
      positive or unknown. CONCLUSION: Peritoneal lavage cytology can detect occult
      carcinoma at the time of PO and should be performed at PO. The significance of
      occult carcinoma detected by either histopathologic or cytopathologic examination
      is uncertain. Whether the prevalence of endosalpingiosis detectable by lavage
      cytology is increased in BRCA mutation-positive patients requires further study.

PMID- 12051866
TI  - The combined evaluation of p27Kip1 and Ki-67 expression provides independent
      information on overall survival of ovarian carcinoma patients.
AB  - OBJECTIVE: Considering the limited and controversial information on the
      significance of the cyclin-dependent kinase inhibitor p27Kip1 in ovarian cancer,
      we conducted a retrospective investigation to clarify the relationships of this
      protein to proliferation rate, clinicopathologic variables, and prognosis of
      epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian
      tumors of low malignant potential (LMP) and 80 primary ovarian adenocarcinomas
      was stained immunohistochemically for p27Kip1, Ki-67 antigen (a marker of cell
      proliferation), and p53 protein. Expression of these markers was correlated with
      clinicopathologic features and with overall survival of patients with
      adenocarcinomas. RESULTS: p27Kip1 levels were significantly higher in LMP tumors
      as well as in low-grade, early-stage, slowly proliferating adenocarcinomas and
      those associated with minimal residual disease (P < 0.001). Decreased p27Kip1
      expression was related to poor overall survival on its own (P = 0.0304) and, when
      combined, to increased proliferation rate (P = 0.0232). More importantly, in
      multivariate analysis, p27Kip1/Ki-67 status was independently related to survival
      (P = 0.040) along with histologic type and FIGO stage. CONCLUSION: Decreased
      p27Kip1 expression is related to several clinicopathologic indicators of
      aggressiveness in ovarian adenocarcinomas and is a major player in cell cycle
      control in these neoplasms. On the contrary, deregulation of the protein does not
      seem to participate in the pathogenesis of LMP tumors. Furthermore, combined
      p27Kip1/Ki-67 expression is a better prognostic marker than expression of p27Kip1
      or Ki-67 alone and supplements the prognostic information gained from traditional
      prognosticators.

PMID- 12051867
TI  - Management of early-stage cervical carcinoma by modified (Type II) radical
      hysterectomy.
AB  - OBJECTIVE: . Surgical management of cervical carcinoma by radical hysterectomy
      has been proven a highly effective method in treating early-stage disease. The
      purpose of this study was to evaluate the efficacy and safety of modified (Type
      II) radical hysterectomy for the treatment of early-stage (I-IIA) cervical
      carcinoma. METHODS: A retrospective analysis of data on 435 patients with
      cervical carcinoma who were managed by modified radical hysterectomy was
      performed. In 145 cases a multimodal approach was used due to the presence of one
      or more risk factors such as lymph node metastasis, CLS involvement, bulky tumor,
      and exocervical extension of disease. Preoperative irradiation was offered to 62
      patients, whereas adjuvant irradiation was offered to 101 patients. RESULTS: The
      mean age of the patients was 42.5 years. The majority of the patients had
      squamous cell cancer (81.6%). The patients were clinically staged as IA (3.2%),
      IB (86.7%), and IIA (10.1%). Positive pelvic lymph nodes were noted in 65
      patients (14.9%). Operative morbidity was minimal, whereas adjuvant radiation
      treatment had no impact on the disease but caused genitourinary morbidity in
      terms of ureteral stricture and postoperative bladder dysfunction (P < 0.001).
      The overall 5-year survival was 88.7%. The most significant predictors related to
      5-year survival were nodal metastasis (P < 0.001), adenomatous histology (P <
      0.001), lesion size (P < 0.001), and CLS involvement (P = 0.004). Adjuvant
      radiation resulted in better local pelvic control of the disease. CONCLUSION: The
      results of our study support the concept that less radical procedures could be
      effectively applied to early-stage cervical carcinoma 4 cm or smaller with
      optimal surgical margins.

PMID- 12051869
TI  - Cell proliferation and apoptosis in BRCA-associated hereditary ovarian cancer.
AB  - OBJECTIVE: The goal was to test the hypothesis that cellular growth properties
      differ between hereditary and sporadic ovarian cancers. METHODS: Cell
      proliferation and apoptosis were assessed in 67 tumors associated with
      deleterious germline BRCA mutations (hereditary) and 69 tumors without BRCA
      mutations (sporadic). Cell proliferation was evaluated by immunohistochemical
      analysis of Ki-67 expression, and apoptosis was assessed using a TUNEL assay.
      RESULTS: The mean number of Ki-67-immunopositive nuclei was significantly higher
      in ovarian cancers from the hereditary group compared with those from the
      sporadic group (P = 0.017). Cell proliferation did not differ significantly
      between BRCA1- and BRCA2-associated hereditary tumors, and apoptosis did not
      differ significantly between the hereditary and sporadic tumors. CONCLUSION:
      These data indicate that ovarian carcinomas associated with germline BRCA
      mutations have a significantly higher growth fraction than sporadic cancers. This
      property may contribute to an improved response to cytotoxic chemotherapy,
      partially accounting for the longer recurrence-free interval and overall survival
      observed in the hereditary group.

PMID- 12051868
TI  - Interleukin-1 system and sex steroid receptor gene expression in human
      endometrial cancer.
AB  - OBJECTIVES: The interleukin-1 system is known to play a pivotal role in human
      physiology and reproduction. In the cycling endometrium, interleukin-1alpha
      activity is controlled by sex steroids and is confined to the perimenstrual
      phase, where it is involved in the events leading to tissue lysis and
      menstruation. Since local tissue degradation is also a feature of malignant
      tumors, our goal was to analyze the gene expression of interleukin-1alpha and
      other interleukin-1 family members and compare it with estrogen receptor alpha,
      estrogen receptor beta, and progesterone receptor mRNA expression in 27
      endometrial carcinomas and 13 normal endometria. METHODS: Endometrial tumor
      tissues were obtained during hysterectomy for endometrial cancer, and normal
      endometrium was sampled in women undergoing surgical procedures for
      nonendometrial pathologies. Gene expression was analyzed by reverse transcription
      polymerase chain reaction. Protein expression was detected and localized by
      immunohistochemical staining. RESULTS: A strong gene expression of interleukin-1
      type I receptor, estrogen recptor alpha, and progesterone receptor was detected
      in all tumor tissues and in the majority of benign endometrial tissues. However,
      in contrast to nonmalignant endometria, variable amounts of interleukin-1beta and
      interleukin-1 receptor antagonist mRNA were also detected in most of the tumor
      samples. Gene expression of interleukin-1alpha and estrogen receptor beta was
      considerably less frequent, with interleukin-1alpha being absent in all peri- and
      postmenopausal endometria and in all but one of the well-differentiated tumors.
      With decreasing differentiation interleukin-1alpha gene expression became more
      frequent. In these cases, interleukin-1alpha protein was detected predominantly
      in epithelial tumor cells of lower-grade tumors. CONCLUSION: We have demonstrated
      the presence of the interleukin-1 system in endometrial malignancies, and found a
      negative correlation between interleukin-1alpha and tumor differentiation. We
      hypothesize that the nonphysiological expression of interleukin-1alpha in less
      differentiated tumors might contribute to their invasiveness and malignant
      behavior.

PMID- 12051870
TI  - Effectiveness of serotonin-receptor antagonist antiemetic therapy over successive
      courses of carboplatin-based chemotherapy.
AB  - PURPOSE: There are extremely limited data available in the general oncology or
      gynecologic cancer literature to document the effectiveness of antiemetic therapy
      over multiple courses of cytotoxic chemotherapy. METHODS: To examine this highly
      clinically relevant issue, we analyzed the complete treatment course of patients
      with gynecologic cancers receiving carboplatin-based chemotherapy regimens who
      had participated in one of four institutional serotonin-receptor antagonist
      antiemetic trials, which had specifically evaluated the benefits of such therapy
      during only the first treatment course. Medical records were reviewed to examine
      the development of emesis during subsequent chemotherapy treatment cycles.
      RESULTS: The 91 patients included in this analysis received a median of 6 courses
      (range 1-18) of carboplatin (initial AUC dose 4, 5, and 6 in 29, 29, and 32
      patients, respectively). All received ondansetron or granisetron plus
      dexamethasone with every treatment course. Complete control of emesis (no acute
      or delayed nausea or vomiting) was experienced by 56 (62%) patients during every
      cycle. Conversely, 20% of women noted one or more episodes of nausea without
      vomiting and 19% developed at least one incidence of vomiting. In no case was
      emesis considered to be severe (grade 3), and no patient required either
      discontinuation of carboplatin or a dose reduction due to the development of
      emesis. CONCLUSION: In the large majority of patients, serotonin-receptor
      antagonist antiemetic therapy, administered in combination with dexamethasone, is
      highly effective over multiple courses in preventing significant carboplatin
      induced nausea and vomiting.

PMID- 12051872
TI  - Gynecological malignancies in elderly patients: is age 70 a limit to standard
      dose chemotherapy? An Italian retrospective toxicity multicentric study.
AB  - OBJECTIVE: One hundred and forty-eight consecutive gynecological oncological
      patients aged >or=70 were administered chemotherapy during the years 1990-2000.
      METHODS: Median age was 73 years (range 70-84). Fifty-five (37.2%) women were
      over 75 years old. One or more comorbid conditions were present in 118 (79.7%)
      patients. Standard schedules were administered to 97.3% of cases, with a total
      number of 1046 cycles of therapy administered (median, 6; range, 1-35, per
      patient). RESULTS: Of a total of 233 chemotherapy regimens globally administered,
      G3-G4 hematological toxicity was documented in 38.2% of cases. Only 10 (6.8%) of
      the 148 patients discontinued treatment because of G3-G4 hematological toxicity.
      No severe nonhematological toxicity was observed. Two dose reductions and three
      treatment delays, but no discontinuation of treatment, were required during
      second-line regimens. Treatment delay >7 days was required in 16.9% of cases.
      CONCLUSIONS: Chronological age did not adversely influence the ability to receive
      aggressive treatment.

PMID- 12051871
TI  - The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene
      products and development of trophoblastic tumor and their predictive significance
      for the malignant transformation of complete hydatidiform mole.
AB  - OBJECTIVE: The aims of this retrospective study by means of immunohistochemical
      staining were (1) to study the expression of c-ras, c-erbB-2, p53, and nm23 gene
      products in complete hydatidiform moles that progress to gestational
      trophoblastic tumor and in those that remit spontaneously after evacuation, and
      (2) to estimate the predictive value of the expression of these four gene
      products in malignant transformation of complete hydatidiform mole. METHODS:
      Clinical data of patients with complete hydatidiform mole were obtained by
      retrospective chart review. Formalin-fixed paraffin sections of 50 cases of
      complete mole that progressed to gestational tumor and 32 cases of complete mole
      that remitted spontaneously were studied immunohistochemically for c-ras, c-erbB
      2, p53, and nm23 proteins. The prognostic value of the proteins for the malignant
      transformation of complete mole was analyzed by multiple logistic regression and
      stepwise logistic estimation. Sections of 30 cases of invasive mole and 19 cases
      of choriocarcinoma were also immunohistologically studied for expression of the
      proteins. RESULTS: Expression of c-erbB-2 and p53 gene products was significantly
      increased and expression of nm23 and c-ras products was remarkably decreased in
      complete hydatidiform moles that progressed into postmolar tumor compared with
      those that remitted spontaneously after evacuation. There was no significant
      difference in the expression of the four genes in invasive mole and in
      choriocarcinoma. A logistic estimation model for predicting malignant
      transformation of complete mole was established based on the expression of gene
      products. When the expression of four gene products was used, the predictive
      sensitivity of the regression model was 86.0%, and the specificity was 75.0%. The
      positive predictive value was 84.3%, the negative predictive value was 77.4%.
      Logistic stepwise regression analysis showed that the altered expression of c
      erbB-2 and nm23 products had strong predictive value, while the expression of c
      ras and p53 products had no significant predictive value for the malignant
      transformation of complete mole. CONCLUSION: The altered expression of c-ras, c
      erbB-2, nm23, and p53 gene products may be important in the pathogenesis of
      gestational trophoblastic tumor. The decreased expression of nm23 protein and
      increased expression of c-erbB-2 protein are strong predictors for the malignant
      transformation of complete mole.

PMID- 12051874
TI  - Paclitaxel and platinum chemotherapy for malignant mixed mullerian tumors of the
      ovary.
AB  - OBJECTIVE: Malignant mixed mullerian tumor (MMMT) of the ovary is a rare tumor
      with a dismal prognosis. The most effective therapy is unknown. The current study
      was undertaken to characterize a group of patients treated as if they had
      aggressive epithelial ovarian tumors, with cytoreductive surgery and combination
      paclitaxel/platinum chemotherapy. METHODS: Retrospective analysis of data
      obtained from tumor registry and hospital records of cases of malignant mixed
      mullerian tumor between January 1, 1992 and January 1, 2000 treated at the
      Massachusetts General Hospital, Brigham and Women's Hospital, and University of
      Vermont was performed. Only patients treated with combination paclitaxel and
      platinum therapy were included in the analysis. Data were collected regarding
      cytoreduction, response to chemotherapy, disease-free interval, and survival.
      RESULTS: Fifty-five patients were identified with MMMT. Twenty-eight patients
      with a clearly ovarian primary had received treatment with combination paclitaxel
      and platinum. Paclitaxel and carboplatin was given as second-line therapy in 2
      patients who had chemoresponsive but incurable disease; the remaining patients
      were treated with paclitaxel and platinum therapy as first-line therapy. These 28
      patients had a median (range) age of 66 (46-84 years) and stage was I in 2
      patients, II in 3, III in 18, and IV in 5. Treatment was generally well
      tolerated. Sixteen patients of 26 treated with paclitaxel and platinum as first
      line therapy achieved a complete clinical response (55%) and 6 patients achieved
      partial response for a total response rate of 72%. Optimal cytoreduction was
      associated with increased time to recurrence (P = 0.001) but not with survival.
      Overall median survival for the 28 patients is 27.1 months. CONCLUSION: Although
      treatment fails many patients, a minority of patients with MMMT in this highly
      selected population do unexpectedly well. An aggressive approach with surgery and
      combination paclitaxel-platinum chemotherapy appears to offer very effective
      therapy.

PMID- 12051873
TI  - Identification of tissue- and cancer-selective promoters for the introduction of
      genes into human ovarian cancer cells.
AB  - OBJECTIVE: One potential limitation of gene therapy for epithelial tumors is the
      lack of tissue or tumor specificity of treatment. Tumor-selective expression of
      gene therapies may avoid deleterious side effects and improve the efficacy of the
      treatment. The aim of this study was to evaluate the tissue and tumor specificity
      of four different potential gene therapy promoters, to determine their usefulness
      in tissue-specific gene therapy of epithelial ovarian carcinomas. METHODS: Three
      potential epithelial cell-selective (hESE1, SLP1, OSP1) and one potential tumor
      selective (hTERT) promoter were placed upstream of a luciferase construct to
      determine relative activity in a wide variety of normal and malignant cell lines.
      Transient transfection and luciferase assays were carried out in 12 epithelial
      ovarian (3 SV40 T antigen-transfected normal and 9 malignant) and 8 control cell
      lines. RESULTS: Luciferase assays revealed that the hTERT promoter presented the
      highest tumor selectivity. hESE1 and SLP1 promoters showed strong epithelial cell
      selectivity (hESE1, 16/17; SLP1, 15/17), with the OSP1 (11/17) promoter
      exhibiting lower epithelial selectivity. Of the potential promoters for gene
      therapy, hTERT promoter exhibited the strongest transcriptional activity in most
      of the tumor cell lines. None of the promoters exhibited strict ovarian
      epithelium selectivity. CONCLUSION: The hTERT promoter may be an optimal promoter
      for a univector gene therapy approach based on its high tumor selectivity.
      Utilization of multiple epithelial cell-specific promoters may result in a more
      tissue-selective gene therapy approach. Using a combination of promoters may
      prevent potential problems due to expression in nonepithelial stem cells that may
      constitutively express hTERT.

PMID- 12051875
TI  - A phase II trial of daily perillyl alcohol in patients with advanced ovarian
      cancer: Eastern Cooperative Oncology Group Study E2E96.
AB  - OBJECTIVE: This was a phase II study of perillyl alcohol in the treatment of
      advanced ovarian cancer. The primary endpoint was to evaluate the 6-month
      progression-free rate of perillyl alcohol as compared with historic controls.
      Secondary objectives were to evaluate the objective response rate, time to
      progression and survival, dropout rate, and number of cycles administered; define
      the qualitative nature of acute and chronic toxicities; and evaluate the effect
      of perillyl alcohol on triglycerides and total, HDL, and LDL cholesterol levels.
      Methods. Women who had received prior platinum-based therapy and had residual or
      recurrent disease were eligible. Perillyl alcohol was administered orally, four
      times daily, at a dose of 1200 mg/m(2). This was repeated until disease
      progression or unacceptable toxicity was experienced. RESULTS: The 6-month
      progression-free rate was 17%. None of the patients achieved a complete or
      partial response. The median progression-free survival was 1.7 months. The median
      overall survival was 9.1 months. Compliance was greater than 90% but
      gastrointestinal toxicity (grade 1-2 nausea, satiety, eructation in 70%) and
      fatigue (grade 1-2 in 40%) were common and limited the ability to escalate the
      dose from 1200 to 1500 mg/m(2). CONCLUSION: Perillyl alcohol administered at this
      dose and formulation did not exhibit signs of extending the time-to-progression
      in patients with advanced ovarian carcinoma.

PMID- 12051876
TI  - Expression of vascular endothelial growth factor in adenocarcinomas of the
      uterine cervix and its relation to angiogenesis and p53 and c-erbB-2 protein
      expression.
AB  - OBJECTIVE: The purpose of this study was to evaluate vascular endothelial growth
      factor (VEGF) expression in adenocarcinomas of the uterine cervix and its
      correlation with clinicopathologic features, angiogenesis, and expression of p53
      and c-erbB-2 proteins. METHODS: Thirty-seven cases of FIGO clinical stage I and
      II adenocarcinoma of the uterine cervix were examined by immunohistochemical
      studies with anti-VEGF, anti-CD34, anti-p53, and anti-c-erbB-2 antibodies.
      Computerized image analysis was used to evaluate microvessel density (MVD).
      RESULTS: Thirty-one tumors (83.8%) were classified as VEGF positive. Six tumors
      (16.2%) showed p53 protein expression while 11 tumors (29.7%) expressed the c
      erbB-2 protein. MVD ranged from 13.3 to 44.8, with a median value of 25.5 (26.9
      +/- 7.5). Tumors expressing VEGF had a significantly higher MVD than those that
      did not express VEGF (P < 0.05). VEGF expression was significantly associated
      with c-erbB-2 protein expression (P < 0.05). The spatial distributions of both
      VEGF expression and c-erbB-2 expression were similar in tumor tissues. In
      univariate log-rank analysis, stage (P = 0.0250), lymphovascular space invasion
      (P = 0.0156), and MVD (P = 0.0360) were associated with shortened survival.
      CONCLUSION: VEGF expression plays a role in promoting angiogenesis in cervical
      adenocarcinomas and c-erbB-2 is likely to be involved in the up-regulation of
      VEGF expression.

PMID- 12051877
TI  - Combination of ifosfamide, paclitaxel, and cisplatin for the treatment of
      metastatic and recurrent carcinoma of the uterine cervix: a phase II study of the
      Hellenic Cooperative Oncology Group.
AB  - OBJECTIVE: Ifosfamide, paclitaxel, and cisplatin have moderate single-agent
      activity in patients with metastatic or recurrent cancer of the uterine cervix.
      We administered a combination of these three agents to a large number of patients
      with metastatic or recurrent cervical cancer to evaluate its activity. METHODS:
      Sixty patients were treated on an outpatient basis with Ifosfamide (I) 1500
      mg/m(2) intravenously over 1 h on Days 1-3, paclitaxel (T) 175 mg/m(2) as a 3-h
      intravenous infusion on Day 1, and cisplatin (P) 75 mg/m(2) intravenously over 2
      h on Day 2 with granulocyte colony-stimulating factor (G-CSF) support. The
      chemotherapy was repeated every 4 weeks for a maximum of six courses. RESULTS:
      Fifty-seven patients received at least two courses of treatment and are evaluable
      for response. Twenty-six patients (46%) achieved an objective response, including
      19% complete and 27% partial responses. The median duration of response was 11.5
      months and the median time to progression and survival for all patients were 8.3
      and 18.6 months, respectively. Patients with excellent performance status, with
      disease recurrence outside the radiation field, and with nonsquamous tumors had
      the highest response rate and best survival. Some degree of neurotoxicity
      occurred in 44% of patients. Grade 3 or 4 toxicity included granulocytopenia in
      26% of patients, anemia in 13%, thrombocytopenia in 7%, and neurotoxicity in 3%.
      CONCLUSION: The ITP regimen is relatively well tolerated and moderately active in
      patients with metastatic carcinoma of the uterine cervix. Patients more likely to
      benefit are those with nonsquamous histology, with excellent performance status,
      and with disease recurrence outside the radiation field.

PMID- 12051879
TI  - Evaluation of prognostic factors and treatment modalities in ovarian cancer
      patients with brain metastases.
AB  - OBJECTIVE: The objective of this study is to evaluate the impact of different
      clinical variables and treatment modalities on survival in patients with brain
      metastases from ovarian carcinoma. METHODS: Methods included: (1) retrospective
      chart review of all patients with ovarian cancer and brain metastases from 1986
      to 2000 at Roswell Park Cancer Institute and (2) Medline search was performed to
      extract data from all published reports with three or more cases of ovarian
      cancer with brain metastases. Cox regression analysis, Kaplan-Meier test, and log
      rank test were used to calculate survival and compare the impacts of clinical
      variables and treatment modalities. RESULTS: Fifteen patients with brain
      metastases out of 1042 women with ovarian carcinoma were identified from our
      institution, an incidence of 1.4%. The median time from initial diagnosis to
      detection of brain metastases was 22 months. Patients who were not treated after
      brain metastasis had a median survival of 0.5 month versus 6 months with therapy.
      In the subgroup of patients treated with a combination of radiation, surgery, and
      chemotherapy, the median survival was 22 months. Literature analysis combined
      with our data generated 124 patients. The only clinically significant variable
      impacting survival was the presence or absence of additional distant recurrence
      with median survivals of 3 and 8 months, respectively (P = 0.005). Among patients
      who received treatment, the combination of radiation and surgery with or without
      chemotherapy appears to be beneficial, with a median survival of 20 months (P <
      0.001). CONCLUSION: Patients with brain metastases from ovarian cancer without
      any evidence of disease in other sites appear to benefit from aggressive combined
      treatment with external radiation and surgery with or without chemotherapy with a
      median survival of 20 months.

PMID- 12051878
TI  - Intraoperative gross examination of myometrial invasion and cervical infiltration
      in patients with endometrial cancer: decision-making accuracy.
AB  - OBJECTIVES: We sought to determine the accuracy of gross evaluation of the depth
      of myometrial invasion and the involvement of the cervix, and its value in
      determining the need for extensive surgery in patients with endometrial
      carcinoma. METHODS: The intraoperative records of 256 patients operated for
      endometrial cancer were used to compare the gross evaluations with the final
      microscopic histopathological findings. In the theater, the uterus was opened and
      inspected after its removal. The depth of myometrial invasion was noted as less
      or greater than 50% using a full-thickness incision through the tumor, while
      cervical involvement was noted as positive or negative, based on extension of the
      tumor below the internal cervical os. Standard statistical calculations were used
      to determine accuracy, sensitivity, specificity, positive and negative predictive
      values, and false-positive and false-negative rates of the method. RESULTS:
      Regarding the depth of myometrial invasion, gross evaluation could accurately
      predict the final result in 88.2% of patients. Sensitivity, specificity,
      positive, and negative predictive values were 83.7, 90.6, 82.8, and 91.1%,
      respectively. False-positive results were noted in 9.4% of cases and false
      negative in 16.3%. Analysis of the characteristics of the false-negative patients
      showed that they had aggressive variant tumors, tumors of advanced grade, and
      tumors that more frequently had developed from an atrophic endometrium. With
      respect to cervical involvement, gross evaluation had an overall accuracy of
      98.5%, 0% false-positive rate, 11.5% false-negative rate, 88.5% sensitivity, 100%
      specificity, 100% positive predictive value, and 98.3% negative predictive value.
      CONCLUSION: Our data suggest that visual gross examination of the uterus provides
      safe and reliable estimates of both myometrial invasion and cervical
      infiltration. So, the surgeon can rely on the procedure to decide the need for
      further operative manipulations.

PMID- 12051880
TI  - Uptake of a cholesterol-rich emulsion by breast cancer.
AB  - OBJECTIVE: Overexpression of low-density lipoprotein (LDL) receptors occurs in
      several cancer cell lines and offers a unique strategy for drug targeting by
      using LDL as vehicle. However, the native lipoprotein is difficult to obtain and
      handle. Previously, we showed that a lipidic emulsion (LDE) similar to the lipid
      structure of native LDL may bind to LDL receptors and be taken up by acute
      myelocytic leukemia cells. We also showed that LDE can also concentrate in
      ovarian cancer tissue. In this study, we tested whether LDE is taken up by breast
      carcinoma. METHODS: LDE labeled with (99m)Tc was injected into 18 breast cancer
      patients, and nuclear medicine images of the tumor and metastatic sites were
      acquired. Subsequently, LDE labeled with [3H]cholesteryl oleate was intravenously
      injected into 14 breast cancer patients 24-30 h before total mastectomy
      procedure. Fragments of normal and of breast cancer tissue excised during surgery
      were lipid extracted with chloroform/methanol and their radioactivity was
      measured in a scintillation solution. RESULTS: (99m)Tc-LDE images of the primary
      tumor and of metastasis sites were obtained in all 18 breast cancer patients. As
      directly measured in the tumor and in the normal mammary tissue, the amount of
      the emulsion radioactive label in the tumor was 4.5 times greater than in the
      normal tissue (range 1.2- to 8.8-fold). CONCLUSION: LDE concentrates much more in
      malignant breast tumor tissue than in the normal tissue. Thus it has potential to
      carry drugs or radionuclides directed against mammary carcinoma cells for
      diagnostic or therapeutic purposes.

PMID- 12051881
TI  - Regulation of estrogen target genes and growth by selective estrogen-receptor
      modulators in endometrial cancer cells.
AB  - OBJECTIVE: Tamoxifen has mixed agonist/antagonist activities, leading to tissue
      specific estrogen-like actions and endometrial cancer. The purpose of this study
      was to evaluate the effects of antiestrogens on the growth of estrogen receptor
      (ER)-positive ECC-1 endometrial cancer cells in vitro and in vivo. METHODS: We
      performed growth studies and luciferase assays using ERE-tK and AP-1 reporters.
      ERalpha protein expression was measured by Western blot after antiestrogen
      treatments. We investigated the actions of antiestrogens on the transcription of
      the pS2 gene in situ measured by Northern blot and the actions of antiestrogens
      on the VEGF protein secreted by ELISA. ERalpha, ERbeta, EGFR, and HER2/neu mRNAs
      were determined by RT-PCR. Last, ECC-1 tumors were developed by inoculation of
      cells into ovariectomized athymic mice and treated with estradiol (E2),
      tamoxifen, raloxifene, and a combination. RESULTS: E2 induced cell proliferation
      while antiestrogens did not. E2 and raloxifene down regulated ERalpha protein; in
      contrast, 4OHT did not. ICI182,780 completely degraded the receptor. ECC-1 cells
      express ERbeta at insignificant levels. Luciferase assays did not show any
      induction in ERE- nor AP-1-mediated transcription by antiestrogens. E2 caused a
      concentration-dependent increase in pS2 mRNA but antiestrogens did not. E2
      increased VEGF expression in a dose-dependent manner and antiestrogens blocked E2
      action. E2 down regulated HER2/neu while 4OHT and raloxifene did not change
      HER2/neu levels compared to control. In addition, EGFR mRNA was down regulated by
      E2 but raloxifene did not change it. Tamoxifen and raloxifene did not promote
      tumor growth in vivo. However, raloxifene (1.5 mg daily) only partially blocked
      E2-stimulated growth. CONCLUSION: Tamoxifen and raloxifene are antiproliferative
      agents and antiestrogens in ECC-1 endometrial cells in vitro and in vivo. The
      observation that selective estrogen-receptor modulators do not down regulate EGFR
      and HER2/neu mRNA may provide a potential role for these oncogenes in the
      development of raloxifene- or tamoxifen-stimulated endometrial cancer. The ECC-1
      cell line could provide important new clues about the evolution of drug
      resistance to tamoxifen and raloxifene.

PMID- 12051882
TI  - Phase II study of mitomycin, doxorubicin, and cisplatin in the treatment of
      advanced uterine leiomyosarcoma: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: Because of preliminary observations favoring the use of mitomycin,
      doxorubicin, and cisplatin (MAP) chemotherapy in leiomyosarcomas, the Gynecologic
      Oncology Group (GOG) decided to conduct a phase II clinical trial of this
      combination regimen in patients with advanced disease. METHODS: Patients with
      histologically confirmed uterine leiomyosarcoma who had not previously received
      cytotoxic drugs were considered for participation in this clinical trial.
      Eligible patients had measurable disease, GOG performance status 0-2, and
      adequate bone marrow, renal, and hepatic function according to standard criteria.
      Mitomycin 8 mg/m(2) and doxorubicin 40 mg/m(2) were each given by iv injection
      followed immediately by cisplatin 60 mg/m(2) in 1 liter of 0.45% saline plus
      mannitol 25 g. Patients who remained free from tumor progression or intolerable
      toxicity received at least three, to a maximum of six, cycles of MAP. RESULTS:
      Forty-one patients were registered, of whom 4 were determined ineligible (wrong
      cell type, 2; wrong site of origin, 1; inadequate pathology material, 1). Thirty
      five of the 37 were evaluable for response after receiving from one to six
      (median three) cycles of MAP. Three patients (9%) achieved a complete response
      and 5 (14%) exhibited a partial response. The most common adverse effects were
      leukopenia (33 patients) and thrombocytopenia (30 patients). Pulmonary toxicity
      was seen in 10 patients and was a factor in the clinical deterioration and death
      of 2. CONCLUSION: MAP is active against advanced uterine leiomyosarcomas, but not
      remarkably so. Despite its low therapeutic index, this novel, possibly
      interactive, combination may serve as a forerunner to regimens that more
      efficiently exploit the enhancement of sarcoma cell kill under hypoxic
      conditions.

PMID- 12051883
TI  - Differential effects of human papillomavirus DNA types on p53 tumor-suppressor
      gene apoptosis in sperm.
AB  - OBJECTIVE: Sperm DNA undergoes apoptotic fragmentation when exposed to HPV DNA.
      Details of the specific gene regions targeted by HPV in sperm are lacking. The
      objective of this study was to determine the integrity of exons 5 and 8 of the
      p53 gene in sperm exposed to HPV DNA. METHODS: Washed sperm were exposed to
      either HLA-DQA1 (control) or HPV type 6b/11, 16, 18, 31, or 33 DNA fragments for
      24 h at 37 degrees C. The integrity of sperm p53 exons 5 and 8 was assessed using
      a novel DNA disc chip assay based on comparative genomic hybridization. RESULTS:
      Fragmentation of exon 5 occurred after exposure to HPV DNA type 18. In contrast,
      only exon 8 was affected by HPV type 16. HPV DNA from type 31 or 33 was without
      effect on the p53 exons. Sperm motility but not hyperactivation was reduced in
      all HPV groups. CONCLUSION: The data suggest that different HPV types
      preferentially degrade different exons of important genes. Decreased motility but
      not hyperactivation in HPV-exposed sperm suggests retention of some fertilizing
      capacity and the possibility of transmitting virus-destabilized genes through
      fertilization.

PMID- 12051884
TI  - Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with
      intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian
      cancer.
AB  - OBJECTIVE: The purpose of this study was to determine the efficacy, tolerability,
      and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous
      (iv) carboplatin and cyclophosphamide. PATIENTS AND METHODS: Twenty-five newly
      diagnosed patients with Stage IC-IV epithelial ovarian cancer received ip
      paclitaxel with iv carboplatin and cyclophosphamide as a first-line treatment.
      Paclitaxel pharmacokinetics was determined during the first cycle on day 1 or 8.
      RESULTS: This regimen was well tolerated, as abdominal pain and hematological
      toxicities were minor, while neurotoxicity grade I/II was reported in only 20%
      and myalgia in 24% of patients and were fully reversible. After treatment 13 of
      18 (72%) of the patients had no evidence of disease. At a median follow-up of 30
      months patients with residual disease after surgery (n = 10) had a median
      progression-free survival (PSF) of 13 months; for the optimally debulked group (n
      = 15) the actuarial PFS was 60% at 48 months. The elimination of paclitaxel from
      the peritoneal cavity and plasma followed first-order kinetics and was not
      influenced by adding carboplatin with cyclophosphamide. CONCLUSION: This regimen
      was well tolerated, with minimal hematologic or neurotoxicity, and allowed the
      application of a triple-drug schedule without compromising dose intensity. To
      judge its efficacy, comparison with a standard iv paclitaxel-based schedule
      should be performed in a formal phase III study.

PMID- 12051885
TI  - Down-regulation of p27 is associated with malignant transformation and aggressive
      phenotype of cervical neoplasms.
AB  - OBJECTIVES: p27Kip1 (p27) is a member of the cyclin-dependent kinase inhibitor
      family. The level of p27 protein expression decreases during tumor development
      and progression in some epithelial tumors. To identify the potential implications
      of the p27 gene in the development of cervical carcinoma and explore the clinical
      importance of change in gene expression, we assessed the level of p27 protein in
      precancerous lesions and carcinomas of the cervix. METHODS: In our study, 20 low
      grade squamous intraepithelial lesions (LSIL), 35 high-grade squamous
      intraepithelial lesions (HSIL), 12 microinvasive carcinomas, and 103 invasive
      carcinomas were evaluated. The expression of p27 was studied by
      immunohistochemistry using a monoclonal antibody specific for the protein.
      RESULTS: p27 was expressed in all samples of normal epithelium, LSIL, and HSIL,
      and the mean values of expression were 55.1, 52.8, and 45.4%, respectively.
      Conversely, the expression of p27 was significantly reduced in microinvasive
      (15.9%) and invasive carcinomas (11.2%). Furthermore, loss of p27 expression was
      significantly associated with lymph node metastasis (P = 0.009). However, p27
      down-regulation had no influence on overall survival using univariate analysis.
      CONCLUSIONS: The trend of reduced p27 expression in microinvasive and invasive
      carcinomas suggests that down-regulation of p27 expression is strongly linked to
      neoplastic transformation of cervical epithelium, and inactivation of p27 may be
      an early event in cervical carcinogenesis. Moreover, loss of p27 expression was
      related to lymph node metastasis in cervical carcinoma. These results imply that
      inactivation of p27 is associated with highly aggressive phenotype of cervical
      carcinoma.

PMID- 12051886
TI  - Port site metastasis of ovarian carcinoma remote from laparoscopic surgery for
      benign disease.
AB  - BACKGROUND: The use of laparoscopic surgical procedures has continued to expand
      due to the many advantages that this surgical approach offers. However, as we
      continue to realize the benefits and expand the scope of laparoscopic procedures,
      new complications may occur. CASE: This is the case of a 77-year-old gravida 2
      para 2 who underwent exploratory laparotomy and surgical staging with optimal
      cytoreduction for Stage IIIC papillary serous ovarian carcinoma in February 1998.
      Her past surgical history was significant for total abdominal hysterectomy and
      left salpingo-oophorectomy in 1955 for symptomatic leiomyomata and for a
      laparoscopic cholecystectomy in July 1997. After initial platinum-based
      chemotherapy, she presented with an enlarging nodule at the right upper quadrant
      laparoscopic port site. Fine needle aspiration confirmed recurrent papillary
      serous ovarian carcinoma. After a discussion of her options, she elected to
      undergo surgical resection with postoperative salvage chemotherapy. CONCLUSION:
      Port site recurrences have been previously reported in patients who underwent
      initial surgical evaluation for ovarian carcinoma utilizing the laparoscopic
      approach. However, it is unusual for recurrent cancer to appear in port sites or
      operative incisions not related to the initial cancer surgery. This report serves
      to caution the gynecologic oncologist that the first evidence of recurrence may
      be at a laparoscopic port site from prior benign gynecologic or nongynecologic
      surgery.

PMID- 12051887
TI  - Vulvar basal cell carcinoma: two unusual presentations and review of the
      literature.
AB  - BACKGROUND: Basal cell carcinoma (BCC) of the vulva comprises 2-4% of all vulvar
      cancers. In general, vulvar BCCs tend to grow at slow rates. Nonetheless, they
      may be locally invasive and destructive if they are neglected. Eight cases of
      vulvar BCC metastatic to regional lymph nodes have been documented in the
      literature. CASES: Two unusual cases of vulvar BCC are presented. Case 1 is an 86
      year-old white woman who presented with vulvar BCC metastatic to the femoral
      head. This is the first report of hematogeneous metastasis of vulvar BCC. The
      patient was treated with palliative vulvar resection and radiation to the femoral
      metastasis. At 6 months, she progressed with multiple bony and intraperitoneal
      metastases and died with disease. Case 2 is vulvar BCC in a 90-year-old African
      American woman. She was managed by wide local excision and remains disease free
      to date. CONCLUSION: Vulvar BCCs are rare tumors with an unclear etiology. They
      can be aggressive and are capable of causing significant morbidity and occasional
      mortality if they are neglected or improperly treated. Hematogeneous metastasis
      at presentation appears to result in rapidly progressive disease. The literature
      regarding the pathogenesis, biologic behavior, and treatment of vulvar BCC is
      reviewed.

PMID- 12051888
TI  - Myxoid leiomyosarcoma of the uterus with subsequent pregnancy and delivery.
AB  - BACKGROUND: Myxoid leiomyosarcoma of the uterus is an extremely rare neoplasm. In
      young women with this disease, fertility should be considered in the treatment
      protocol. CASE: A 20-year-old woman presented with a huge pelvic mass originating
      from the uterine wall and showing a histopathology of myxoid leiomyosarcoma. Five
      and one-half years after laparotomy, the recurrent tumor was found and removed.
      Two years after the second operation, she became pregnant, and delivered a
      healthy baby by cesarean section. Multiple recurrent masses were evident and
      removed at cesarean section. She is alive and well without evidence of recurrence
      1 year after delivery. CONCLUSION: The best treatment for this tumor is not
      established. In young women with a desire to bear children, the management is
      more controversial.

PMID- 12051889
TI  - Transvaginal evisceration after radical abdominal hysterectomy.
AB  - BACKGROUND: Intestinal evisceration through the vagina is rare and transvaginal
      evisceration after transabdominal surgery is far more rare. CASE: We present an
      unusual case of a postmenopausal woman who presented with transvaginal
      evisceration of the small bowel after radical abdominal hysterectomy and pelvic
      lymphadenectomy. CONCLUSION: This was a rare case of terminal ileal evisceration
      through a ruptured vaginal cuff after radical hysterectomy and bilateral pelvic
      lymphadenectomy. We performed a delayed closure of the vaginal defect through the
      vagina after manual reduction of the eviscerated small bowel, and the outcome was
      satisfactory.

PMID- 12051890
TI  - Radical vaginal trachelectomy after supracervical hysterectomy.
AB  - BACKGROUND: Radical vaginal trachelectomy (RVT) is an acceptable approach when
      applied toward a select group of patients with early stage cervical carcinoma. It
      is less invasive, can maintain fertility, and can be ideal in patients with
      significant comorbid factors compared to abdominal approaches. A small subset of
      patients with a previous supracervical hysterectomy can pose a surgical dilemma.
      CASE: An 81-year-old woman with a history of severe cardiac disease on routine
      gynecological examination was found to have adenocarcinoma in situ with a focus
      suspicious for invasion of the cervical stump diagnosed by cone biopsy. She
      previously had a supracervical hysterectomy for benign disease of the uterus. A
      RVT was performed as definitive treatment and the patient recovered without
      complications. CONCLUSION: In the rare case that presents with a history of
      supracervical hysterectomy, RVT with some technical modifications can still be
      considered as a therapeutic option for early stage cervical carcinoma.

PMID- 12051892
TI  - A high-affinity ammonium transporter from the mycorrhizal ascomycete Tuber
      borchii.
AB  - An ammonium transporter cDNA, named TbAMT1, was isolated from the ectomycorrhizal
      ascomycetous truffle Tuber borchii. The polypeptide encoded by TbAMT1 (52 kDa)
      functionally complements ammonium uptake-defective yeast mutants and shares
      sequence similarity with previously characterized ammonium transporters from
      Saccharomyces (Mep) and Arabidopsis (AtAMT1). Structural characteristics common
      to the Mep/Amt family and peculiar features of the Tuber transporter have been
      evidenced by a detailed topological model of the TbAMT1 protein, which predicts
      11 transmembrane helices with an N terminus(OUT)/C terminus(IN) orientation. As
      revealed by uptake/competition experiments conducted in yeast, TbAMT1 is a high
      affinity transporter with an apparent K(m) for ammonium of 2 microM. The TbAMT1
      mRNA was very slowly, yet specifically upregulated in nitrogen-deprived T.
      borchii mycelia. Instead, a much faster return to basal expression levels was
      observed upon resupplementation of either ammonium or nitrate, which thus appear
      to be utilized as equally effective nitrogen sources by Tuber mycelia.

PMID- 12051891
TI  - Predicting the distribution, conservation, and functions of SNAREs and related
      proteins in fungi.
AB  - Hyphal tip growth, the hallmark of the fungi, requires highly polarized and
      localized exocytosis, but how this requirement is met is unknown. Members of
      conserved protein families called SNAREs and Rabs mediate vesicle trafficking and
      fusion at virtually every step of the intracellular pathway in all examined
      eukaryotes. We have searched the available nearly complete fungal genomes,
      established the presence or absence of members of the SNARE and Rab families in
      these genomes, and predicted their evolutionary relationships to one another.
      Comparisons with the extensively studied Saccharomyces cerevisiae indicate that,
      in general, most of the members of these families (including those involved in
      mediating exocytosis) are conserved. The presence of exceptional SNAREs and Rabs
      in some fungi that are not conserved in S. cerevisiae may be indicative of
      specialized steps that occur in these fungi. The implications of these findings
      for current tip growth models are discussed.

PMID- 12051893
TI  - Mutation and functional analysis of the Aspergillus nidulans ammonium permease
      MeaA and evidence for interaction with itself and MepA.
AB  - The movement of ammonium across biological membranes is mediated in both
      prokaryotic and eukaryotic systems by ammonium transport proteins which
      constitute a family of related sequences (called the AMT/MEP family).
      Interestingly, recent evidence suggests that human and mouse Rhesus proteins
      which display significant relatedness to AMT/MEP sequences may function as
      ammonium transporters. To add to the functional understanding of ammonium
      transport proteins, the sequence changes in 37 loss-of-function mutations within
      the Aspergillus nidulans ammonium permease gene, meaA, were characterized.
      Together with the identification of conserved AMT/MEP residues and regions, the
      mutational analysis predicted regions important for uptake activity.
      Specifically, a major facilitator superfamily like motif (161-GAVAERGR-168 in
      MeaA) may be important for the translocation of ammonium across the membrane as
      may the conserved Pro186 residue. A specific Gly447 to Asp mutation was
      introduced into MeaA and this mutant protein was found to trans-inhibit the
      activity of endogenous MeaA and the other A. nidulans ammonium transporter, MepA.
      These results suggest that MeaA may interact with itself and with MepA, although
      any hetero-interaction is not required for ammonium transport function. In
      addition, cross-feeding studies showed that MeaA and to a lesser extent MepA are
      also required for the retention of intracellular ammonium.

PMID- 12051894
TI  - Mannan changes induced by 3-methyl-5-aminoisoxazole-4-thiocyanate, a new azole
      derivative, on Epidermophyton floccosum.
AB  - The antifungal activity of 3-methyl-5-aminoisoxazole-4-thiocyanate, a new azole
      derivative, was studied on the dermatophyte Epidermophyton floccosum. The
      compound strongly inhibited the in vitro growth of two different strains of the
      fungus and even induced profound morphogenetic anomalies. Optical and electron
      microscopy showed that such treatment targets the endomembrane system,
      particularly the plasmalemma, causing abnormal extrusion of the wall mannans.
      This results in improper arrangement of the different parietal materials; the
      walls are thus weak and subject to subapical rupture which terminates cell growth
      and elongation of the hypha. The morphological results and the preliminary
      biochemical data on fungal sterols suggest that this compound employs an action
      mechanism similar to that of other azoles used in therapy.

PMID- 12051895
TI  - The use of direct cDNA selection to rapidly and effectively identify genes in the
      fungus Aspergillus fumigatus.
AB  - Aspergillus fumigatus is one of the causes of invasive lung disease in
      immunocompromised individuals. To rapidly identify genes in this fungus,
      including potential targets for chemotherapy, diagnostics, and vaccine
      development, we constructed cDNA libraries. We began with non-normalized
      libraries, then to improve this approach we constructed a normalized cDNA library
      using direct cDNA selection. Normalization resulted in a reduction of the
      frequency of clones with highly expressed genes and an enrichment of
      underrepresented cDNAs. Expressed sequence tags generated from both the original
      and the normalized libraries were compared with the genomes of Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, and Candida albicans, indicating that a
      large proportion of A. fumigatus genes do not have orthologs in these fungal
      species. This method allowed the expeditious identification of genes in a fungal
      pathogen. The same approach can be applied to other human or plant pathogens to
      rapidly identify genes without the need for genomic sequence information.

PMID- 12051896
TI  - Endopolygalacturonase is encoded by a multigene family in the basidiomycete
      Chondrostereum purpureum.
AB  - The basidiomycete Chondrostereum purpureum produces several plant cell wall
      degrading enzymes, including endopolygalacturonase (endoPG). Degenerate
      oligonucleotide primers were designed according to conserved regions of endoPG
      genes from various fungi, plants, and bacteria and used to amplify members of
      this gene family from C. purpureum. Four different amplification products showed
      significant similarity to known endoPGs and were used as hybridization probes to
      screen a library of genomic DNA sequences and to retrieve five full-length endoPG
      genes (epgA, epgB1, epgB2, epgC, and epgD). The identities between the deduced
      polypeptides for epgA, epgB1, epgC, and epgD ranged from 61.8 to 80.0%, while the
      deduced polypeptides for epgB1 and epgB2 shared 97.1% identity. Phylogenetic
      analysis suggested that the duplication of existing endoPG genes occurred after
      the divergence of the ascomycetes and basidiomycetes. C. purpureum is the first
      basidiomycete fungus for which the endoPG gene family has been described.

PMID- 12051897
TI  - The first three-dimensional structure of phosphofructokinase from Saccharomyces
      cerevisiae determined by electron microscopy of single particles.
AB  - Phosphofructokinaseis a key regulatory enzyme of the glycolytic pathway. We have
      determined the structure of this enzyme from Saccharomyces cerevisiae to a
      resolution of 2.0 nm. This is the first structure available for this family of
      enzymes in eukaryotic organisms. Phosphofructokinase is an octamer composed of
      4alpha and 4beta subunits arranged in a dihedral point group symmetry D(2). The
      enzyme has a very open and elongated structure, with dimensions of 24 nm in
      length and 17 nm in width. The final structure, calculated from 0 degrees tilt
      projections of the molecule at random orientations using as reference the volume
      obtained by the random conical reconstruction technique in ice, has allowed us to
      discern the shapes of the subunits and their mutual arrangement in the octamer.

PMID- 12051898
TI  - Morphological changes during conoid extrusion in Toxoplasma gondii tachyzoites
      treated with calcium ionophore.
AB  - Treatment of tachyzoites of Toxoplasma gondii with the calcium ionophore A23187
      induced dramatic ultrastructural changes that were observed by light and electron
      microscopy. Light microscopy showed a higher percentage (22%) of tachyzoites with
      the conoid extruded when compared to control parasites. Electron microscopy
      confirmed the conoid extrusion by both transmission and scanning electron
      microscopy. Freeze-fracture replicas showed that the plasma membrane adjacent to
      cytoplasmic dense granules appeared devoid of intramembranous particles. Membrane
      limited vesicles and filopodium-like structures at the cell surface were observed
      in treated cells. 3-D reconstruction from serial sections confirmed the data and
      showed a heterogeneity in dense granule shape not reported in control cells.

PMID- 12051899
TI  - Combining electron microscopic with x-ray crystallographic structures.
AB  - Analgorithm has been developed for placing three-dimensional atomic structures
      into appropriately scaled cryoelectron microscopy maps. The first stage in this
      process is to conduct a three-dimensional angular search in which the center of
      gravity of an X-ray crystallographically determined structure is placed on a
      selected position in the cryoelectron microscopy map. The quality of the fit is
      measured by the sum of the density at each atomic position. The second stage is
      to refine the three angles and three translational parameters for the best
      (usually 25 to 100) fits. Useful criteria for this refinement include the sum of
      densities at atomic sites, the lack of atoms in negative or low density, the
      absence of atomic clashes between symmetry-related positions of the atomic
      structure, and the distances between identifiable features in the map and their
      positions on the fitted atomic structure. These refinements generally lead to a
      convergence of the originally chosen, top scoring fits to just a few (about 3 to
      8) acceptable possibilities. Usually, the best remaining fit is clearly superior
      to any of the others.

PMID- 12051900
TI  - Automatic alignment of transmission electron microscope tilt series without
      fiducial markers.
AB  - Accurate image alignment is needed for computing three-dimensional
      reconstructions from transmission electron microscope tilt series. So far, the
      best results have been obtained by using colloidal gold beads as fiducial
      markers. If their use has not been possible for some reason, the only option has
      been the automatic cross-correlation-based registration methods. However, the
      latter methods are inaccurate and, as we will show, inappropriate for the whole
      problem. Conversely, we propose a novel method that uses the actual 3D motion
      model but works without any fiducial markers in the images. The method is based
      on matching and tracking some interest points of the intensity surface by first
      solving the underlying geometrical constraint of consecutive images in the tilt
      series. The results show that our method is near the gold marker alignment in the
      level of accuracy and hence opens the way for new opportunities in the analysis
      of electron tomography reconstructions, especially when markers cannot be used.

PMID- 12051901
TI  - Semi-automated icosahedral particle reconstruction at sub-nanometer resolution.
AB  - Electron cryomicroscopy of large macromolecular complexes is becoming an
      increasingly powerful tool for revealing three-dimensional structures without the
      need for crystallization. The execution of image processing, however, requires
      experience and is error-prone due to the need for a human operator to carry out
      interactive and repetitive processes. We have designed an approach which is
      intended to make image processing simple and rapid, both for experts and for
      novice users. We demonstrate this approach using the well-established
      reconstruction scheme for icosahedral particles. Finally, we implement semi
      automated virus reconstruction (SAVR), an expert system that integrates the most
      CPU intensive and iterative steps using the scripting language Python. SAVR is
      portable across platforms and has been parallelized to run on both shared and
      distributed memory platforms. SAVR also allows the incorporation of new
      algorithms and facilitates the management of the increasingly large data sets
      needed to achieve higher resolution reconstructions. The package has been
      successfully applied to several data sets and shown capable of generating
      icosahedral reconstructions to sub-nanometer resolutions (7-10 A ).

PMID- 12051903
TI  - Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible
      explanation for molecular filtering?
AB  - The luminal surface of endothelial cells is lined with the glycocalyx, a network
      structure of glycoproteins probably 50 to 100 nm thick. It has been suggested
      that a relatively regular fibre-matrix structure may be responsible for the
      ultrafiltration properties of microvascular walls, both when the endothelium is
      continuous and when it is fenestrated. Positive structural evidence demonstrating
      an underlying periodicity in the glycocalyx has been hard to obtain. Here we
      present structural analysis of glycocalyx samples prepared in a variety of ways
      for electron microscopy. Using computed autocorrelation functions and Fourier
      transforms of representative areas of the electron micrograph images, we show
      that there is an underlying three-dimensional fibrous meshwork within the
      glycocalyx with characteristic spacings of about 20 nm. Together with a fibre
      diameter consistent with our observations of about 10-12 nm, the 20-nm spacing
      provides just the size regime to account satisfactorily for the observed
      molecular filtering; the observations are consistent with the fibre matrix model.
      We also show that the fibrous elements may occur in clusters with a common
      intercluster spacing of about 100 nm and speculate that this may reveal
      organisation of the glycocalyx by a quasi-regular submembranous cytoskeletal
      scaffold.

PMID- 12051902
TI  - An automatic particle pickup method using a neural network applicable to low
      contrast electron micrographs.
AB  - Three-dimensional reconstruction from electron micrographs requires the selection
      of many single-particle projection images; more than 10 000 are generally
      required to obtain 5- to 10-A structural resolution. Consequently, various
      automatic detection algorithms have been developed and successfully applied to
      large symmetric protein complexes. This paper presents a new automated particle
      recognition and pickup procedure based on the three-layer neural network that has
      a large application range than other automated procedures. Its use for both faint
      and noisy electron micrographs is demonstrated. The method requires only 200
      selected particles as learning data and is able to detect images of proteins as
      small as 200 kDa.

PMID- 12051905
TI  - Crystal structure of the C. perfringens alpha-toxin with the active site closed
      by a flexible loop region.
AB  - Clostridium perfringens biotype A strains are the causative agents of gas
      gangrene in man and are also implicated as etiological agents in sudden death
      syndrome in young domestic livestock. The main virulence factor produced by these
      strains is a zinc-dependent, phosphatidylcholine-preferring phospholipase C
      (alpha-toxin). The crystal structure of alpha-toxin, at pH 7.5, with the active
      site open and therefore accessible to substrate has previously been reported, as
      has calcium-binding to the C-terminal domain of the enzyme at pH 4.7. Here we
      focus on conformation changes in the N-terminal domain of alpha-toxin in crystals
      grown at acidic pH. These changes result in both the obscuring of the toxin
      active site and the loss of one of three zinc ions from it. Additionally, this
      "closed" form contains a small alpha helix, not present in the open structure,
      which hydrogen bonds to both the N and C-terminal domains. In conjunction with
      the previously reported findings that alpha-toxin can exist in active and
      inactive forms and that Thr74Ile and Phe69Cys substitutions markedly reduced the
      haemolytic activity of the enzyme, our work suggests that these loop
      conformations play a critical role in the activity of the toxin.

PMID- 12051904
TI  - Progress with parasite plastids.
AB  - This review offers a snapshot of our current understanding of the origin,
      biology, and metabolic significance of the non-photosynthetic plastid organelle
      found in apicomplexan parasites. These protists are of considerable medical and
      veterinary importance world-wide, Plasmodium spp., the causative agent of malaria
      being foremost in terms of human disease. It has been estimated that
      approximately 8% of the genes currently recognized by the malarial genome
      sequencing project (now nearing completion) are of bacterial/plastid origin. The
      bipartite presequences directing the products of these genes back to the plastid
      have provided fresh evidence that secondary endosymbiosis accounts for this
      organelle's presence in these parasites. Mounting phylogenetic evidence has
      strengthened the likelihood that the plastid originated from a red algal cell.
      Most importantly, we now have a broad understanding of several bacterial
      metabolic systems confined within the boundaries of the parasite plastid. The
      primary ones are type II fatty acid biosynthesis and isoprenoid biosynthesis.
      Some aspects of heme biosynthesis also might take place there. Retention of the
      plastid's relict genome and its still ill-defined capacity to participate in
      protein synthesis might be linked to an important house-keeping process, i.e.
      guarding the type II fatty acid biosynthetic pathway from oxidative damage.
      Fascinating observations have shown the parasite plastid does not divide by
      constriction as in typical plants, and that plastid-less parasites fail to thrive
      after invading a new cell. The modes of plastid DNA replication within the phylum
      also have provided surprises. Besides indicating the potential of the parasite
      plastid for therapeutic intervention, this review exposes many gaps remaining in
      our knowledge of this intriguing organelle. The rapid progress being made shows
      no sign of slackening.

PMID- 12051906
TI  - A new crystal form of the NK1 splice variant of HGF/SF demonstrates extensive
      hinge movement and suggests that the NK1 dimer originates by domain swapping.
AB  - NK1 is a splice variant of the polypeptide growth factor HGF/SF that consists of
      the N terminal (N) and first kringle (K) domains and retains receptor binding and
      signalling. While NK1 behaves as a monomer in solution, two independent
      crystallographic structures have previously shown an identical, tightly packed
      dimer. Here we report a novel orthorhombic crystal form of NK1 at 2.5 A
      resolution in which four NK1 protomers are packed in two distinct dimers in the
      asymmetric unit. Although the basic architecture of the new NK1 dimers is similar
      to the two described earlier, the new crystal form demonstrates extensive hinge
      movement between the N and K domain that leads to re-orientation of the receptor
      binding sites. The hinge bending is evidence of the paucity of strong
      interactions between domains within the protomer, in contrast to the extensive
      interactions between protomers in the dimer. These observations are consistent
      with domain swapping in the dimer, such that the interdomain interactions of the
      monomer are replaced by equivalent interprotomer interactions in the dimer and
      offer a route for protein engineering of NK1 variants which may act as receptor
      antagonists.

PMID- 12051908
TI  - Site-specific recombination in eukaryotic cells mediated by mutant lambda
      integrases: implications for synaptic complex formation and the reactivity of
      episomal DNA segments.
AB  - Mutant lambda integrases catalyze site-specific DNA recombination in the absence
      of accessory factors IHF, XIS, and negative DNA supercoiling. Here we investigate
      the effects that a human cellular environment exerts on these reactions in order
      to (i) gain further insights into mechanistic aspects of recombination in
      eukaryotic cells and (ii) to further develop the Int system for biotechnological
      applications. First, we compared intra- and intermolecular integrative as well as
      excisive recombination pathways on episomal substrates after co-transfection with
      recombinase expression vectors. Our results demonstrate that, within 24 hours
      after transfection, intermolecular recombination by mutant integrase is at least
      as efficient as intramolecular recombination. Second, a significant
      intermolecular recombination activity was observed between two copies of a
      recombination site containing only the 21 bp comprising core-type DNA sequence.
      This basic activity was stimulated several-fold when arm-type DNA sequences were
      present in addition to core sites. Therefore, one recombination pathway in human
      cells involves mutant integrases bound solely at core sites, which is reminiscent
      of the Flp/FRT and Cre/loxP pathways. The stimulatory effect of arm-type
      sequences could be explained by an increase in integrase concentration in the
      vicinity of core sites. We show, in addition, that an N-terminal truncated mutant
      integrase exhibited only a very weak recombinogenic activity in a eukaryotic
      background. This result strengthens a functional role for the N-terminal domain
      in recombination in addition to its arm-type DNA-binding activity. Finally, we
      demonstrate that low level integrative recombination by wild-type integrase is
      stimulated when purified integration host factor is co-transfected. This
      corroborates our previous conclusion that sufficient amounts of eukaryotic
      protein co-factors, which could functionally replace IHF, are not present in
      human cells. It also provides a potential means to control site-specific
      recombination in eukaryotic cells.

PMID- 12051907
TI  - A bipartite bacteriophage T4 SOC and HOC randomized peptide display library:
      detection and analysis of phage T4 terminase (gp17) and late sigma factor (gp55)
      interaction.
AB  - HOC and SOC are dispensable T4 capsid proteins that can be used for phage display
      of multiple copies of peptides and proteins. A bipartite phage T4 peptide library
      was created by displaying on tetra-alanine linker peptides five randomized amino
      acids from the carboxyl-terminus of SOC and five randomized amino acids from the
      amino terminus of HOC. The bipartite library was biopanned against the phage T4
      terminase large subunit gp17 to identify T4 gene products that may interact with
      the terminase. The sequences of selected phages displayed matches to those T4
      gene products previously known by genetic and biochemical criteria to interact
      with gp17: gp20 (portal protein), gp32 (single-stranded DNA binding protein),
      gp16 (terminase small subunit), and gp17 (self). In addition, matches were found
      to gp55 (T4 late sigma factor), gp45 (sliding clamp), gp44 (clamp loader), gp2
      (DNA end protein), and gp23 (major capsid protein). Abundant amino acid sequence
      matches were found to aa region 118-134 of gp55. Immunoprecipitation and affinity
      column chromatography demonstrated direct binding of gp17 and gp55; moreover,
      gp17 bound specifically to a column-coupled peptide corresponding to gp55
      residues 111-136. Measurements of gene 17 and other mRNA levels in mutant
      infected bacteria did not support a role of gp17-gp55 interaction in regulation
      of terminase or other late gene transcription. However, whereas DNA concatemers
      that accumulate in prohead and terminase defective phage T4 infections could be
      packaged in vitro to approximately 10% wild-type efficiency, 55am33am defective
      concatemeric DNA was packaged at least 100-fold less efficiently. Moreover, gp55
      residues 111-136 peptide specifically blocked DNA packaging in vitro. These
      results suggest that the T4 terminase interaction with T4 late sigma factor gp55
      plays a role in DNA packaging in vivo. The gp55 interaction may function to load
      the terminase onto DNA for packaging.

PMID- 12051909
TI  - The influence of sequence divergence between alleles of the human MS205
      minisatellite incorporated into the yeast genome on length-mutation rates and
      lethal recombination events during meiosis.
AB  - Certain minisatellites exhibit hypervariability with respect to the number of
      repeat units and, thus, allele length. Such polymorphism is generated by germline
      specific recombinational events that occur at high frequencies and lead to the
      gain or loss of repeat units. In order to elucidate the molecular details of
      mutagenesis in minisatellites, we have integrated human minisatellites into the
      yeast genome in the vicinity of a hotspot for meiotic double-strand breaks
      (DSBs). Here, we describe the results of tetrad analyses of mutations in the
      human MS205 minisatellite in yeast strains heterozygous for alleles composed of
      51 and 31 repeat units, as well as in a strain homozygous for the same 51 repeat
      unit allele. The length-mutation rate was twice as high in the heterozygous
      strain as in the homozygous strain, suggesting that sequence divergence between
      alleles enhances the generation of length mutations. In the case of
      heterozygotes, the frequency of length mutants resulting from inter-allelic
      exchange was significantly higher in tetrads with three viable spores than in
      tetrads with four viable spores, indicating that there is a higher probability
      for spore mortality in tetrads originating from meioses during which inter
      allelic exchange of repeat units occurs. In an attempt to explain these findings,
      we propose a model for minisatellite mutation involving recombination, in which
      sequence divergence between alleles results in a heteroduplex containing numerous
      mismatches. We suggest that convergent mismatch-repair tracts in this
      heteroduplex give rise to a DSB that may be repaired by an additional round of
      recombination resulting in mutation of a third allele, or be lethal if such
      recombination fails. It appears probable that the formation of such additional
      mutants is the major explanation for the difference in meiotic length-mutation
      rates between the heterozygous and homozygous yeast strains, and that this
      phenomenon contributes to high germline length-mutation frequencies at
      minisatellites in humans.

PMID- 12051910
TI  - Limitation of ribosomal protein L11 availability in vivo affects translation
      termination.
AB  - Historically referred to as "the GTPase center", the L11 binding region (L11BR)
      of Escherichia coli 23 S rRNA is a highly conserved structure that has been
      implicated in several essential functions during protein synthesis. Here, in vivo
      expression of an RNA fragment containing that structure was found to affect
      translation termination in a codon-specific manner. The cause of these effects
      appeared to be titration of ribosomal protein L11, since normal phenotypes could
      be restored by simultaneous overproduction of wild-type L11 but not mutant L11.
      Subsequently, altered termination phenotypes were produced when the availability
      of L11 was limited by overexpression of RNA antisense to L11 mRNA and, finally,
      by inactivation of the chromosomal L11 gene, and they too were reversible by
      simultaneous expression of cloned L11. Our results indicate that in the intact
      cell the L11BR is an integral functional unit important for translation
      termination and that the presence of L11 in ribosomes is required for UAG
      dependent termination and is somewhat inhibitory of UGA-dependent termination.

PMID- 12051912
TI  - Recognition of DNA by p53 core domain and location of intermolecular contacts of
      cooperative binding.
AB  - We present an analysis by NMR of a 58 kDa complex of the core domain of the
      tumour suppressor p53 with DNA that complements and extends the crystal structure
      analysis. Binding of specific DNA caused significant chemical shifts of residues
      on the DNA-binding interface that translated into the beta-sheet of the protein.
      Binding of non-specific DNA caused weak but qualitatively the same shifts,
      corresponding to weaker binding interactions. The observed chemical shift
      differences correlate with frequency of cancer-inducing mutations, suggesting
      that the affected residues contribute to the stability of p53 core domain-DNA
      complex. We also identified two affected regions on the surface of the protein:
      helix 1 (residues V173-C182) plus G244 and residues L114-T118, which may
      represent a dimerisation interface.

PMID- 12051911
TI  - Both temperature and medium composition regulate RNase E processing efficiency of
      the rpsO mRNA coding for ribosomal protein S15 of Escherichia coli.
AB  - Cleavage by RNase E is believed to be the rate-limiting step in the degradation
      of many RNAs. These cleavages are modulated by 5' end-phosphorylation, folding
      and translation of the mRNA in question. Here, we present data suggesting that
      these cleavages are also regulated by environmental conditions. We report that
      rpsO mRNA, 15 minutes after a shift to 44 degrees C, is stabilized in cells grown
      in minimal medium. This stabilization is correlated with a reduction in the
      efficiency of the RNase E cleavage which initiates its decay. We also observe the
      appearance of RNA fragments previously detected following RNase E inactivation
      and a defect in the adaptation of RNase E concentration. These observations,
      coupled to the fact that RNase E overproduction slightly reduces the accumulation
      of the rpsO mRNA, suggest that this stabilization is caused in part by a
      limitation in RNase E concentration. An increase in the steady-state level of
      rpsT mRNA is also observed following a shift to 44 degrees C in minimal medium;
      however, processing of the 9 S rRNA precursor is not affected under these
      conditions. We thus propose that RNase E concentration changes in the cell in
      response to environmental conditions and that these changes can selectively
      affect the processing and the stability of individual mRNAs. Our data also
      indicate that the efficiency of cleavage of the rpsO mRNA by RNase E is modified
      by other factor(s) which remain to be identified.

PMID- 12051913
TI  - DNA polymerase theta purified from human cells is a high-fidelity enzyme.
AB  - With the aim to identify unconventional DNA polymerases from human cells, we have
      set up a special assay to fractionate HeLa extracts based on the ability (i) to
      bypass DNA lesions, (ii) to be resistant to aphidicolin and an inhibitory
      antibody against pol alpha and (iii) to be non-responsive to proliferating cell
      nuclear antigen. After eight different chromatographic steps, an aphidicolin
      resistant DNA polymerase activity was obtained that was able to utilize either
      undamaged or abasic sites-containing DNA with the same efficiency. Biochemical
      characterization and immunoblot analysis allowed its identification as the human
      homologue of DNA polymerase theta (hpol theta), whose cDNA has been cloned by
      homology with the mus308 gene of Drosophila melanogaster but still awaited
      detailed biochemical characterization. The purified hpol theta was devoid of
      detectable helicase activity, possessed a 3'-->5' exonuclease activity and showed
      biochemical properties clearly distinct from any other eukaryotic DNA polymerase
      known so far. Misincorporation and fidelity assays showed that: (i) hpol theta
      was able to catalyze efficiently DNA synthesis past an abasic site; and (ii) hpol
      theta showed high fidelity. Our findings are discussed in light of the proposed
      physiological role of hpol theta.

PMID- 12051914
TI  - Interactions of protein complexes on supercoiled DNA: the mechanism of selective
      synapsis by Tn3 resolvase.
AB  - "Looping" interactions of distant sites on DNA molecules, mediated by DNA-binding
      proteins, feature in many regulated genetic processes. We used plasmids
      containing up to six res recombination sites for Tn3 resolvase to analyse looping
      interactions (synapsis) in this system. We observed that in plasmids with four or
      more res sites, certain pairs of sites recombine faster than others. The relative
      rates of recombination depend on the number, relative orientation, and
      arrangement of the sites. To account for the differences in rate, we propose that
      pairing interactions between resolvase-bound res sites are in a state of rapid
      flux, leading to configurations in which the maximum number of sites within each
      supercoiled substrate molecule are synapsed in a topologically simple
      arrangement. Recombination rates reflect the steady state concentrations of these
      synapse configurations. Our results are at variance with models for selective
      synapsis that rely on ordered motions within supercoiled DNA, "slithering" or
      "tracking", but are compatible with models that call for reversible synapsis of
      pairs of sites by random collision, followed by formation of an interwound
      productive synapse.

PMID- 12051915
TI  - Synapsis of Tn3 recombination sites: unpaired sites destabilize synapses by a
      partner exchange mechanism.
AB  - Catalysis of site-specific recombination is preceded by the formation of a
      synapse comprising two DNA sites and multiple subunits of the recombinase,
      together with other "accessory" proteins in some cases. We investigated the
      stability of synapses of Tn3 resolvase-bound res recombination sites, in plasmids
      containing either two or three res sites. Although synapses are long-lived in
      plasmids with just two res sites, persisting for tens of minutes, a synapse of
      any two sites is relatively short-lived in plasmids with three res sites. The
      three alternative pairwise synapses that can be formed in three-res plasmids re
      assort rapidly relative to the rate of recombination. We propose a "partner
      exchange" mechanism for this re-assortment, involving direct attack on a synapse
      by an unpaired res site. This mechanism reconciles studies on selective synapsis
      in multi-res substrates, which imply rapid interchange of synaptic pairings, with
      studies indicating that synapses of two Tn3res sites are stable.

PMID- 12051916
TI  - DNA-repair by photolyase reveals dynamic properties of nucleosome positioning in
      vivo.
AB  - Nucleosomes exert a repressive influence on the biological functions of DNA by
      restricting the access of proteins to DNA. To investigate how intrinsic
      properties of nucleosomes modulate DNA-accessibility in vivo, we studied DNA
      repair by photolyase in the yeast URA3 gene. Formation of DNA lesions
      (cyclobutane pyrimidine dimers, CPDs) and photolyase activity are controlled
      precisely by light. Preceding work revealed that photolyase repairs nucleosome
      free DNA rapidly, while repair of nucleosomes is inhibited severely. The high
      resolution data presented here show slow repair in the center of nucleosomes and
      a gradual increase towards the periphery. This pattern was observed in all
      nucleosomes and demonstrates that dynamic properties facilitate DNA
      accessibility. Since the URA3 nucleosomes can occupy alternate positions, the
      repair data are most consistent with nucleosome mobility that moves CPDs in
      linker DNA where they are repaired rapidly. A partial and transient unfolding or
      disruption of nucleosomes, however, may not be excluded. In addition, repair
      heterogeneity was found between closely spaced sites, indicating that structural
      properties of nucleosomes contribute to damage processing. Moreover, nucleosome
      specific modulation of photolyase was found on the transcribed and non
      transcribed strand. This is in contrast to homogeneous repair of the transcribed
      strand by nucleotide excision repair, and reveals fundamental differences in how
      both repair systems interact with nucleosomes and transcription.

PMID- 12051917
TI  - ATF/CREB sites present in sub-telomeric regions of Saccharomyces cerevisiae
      chromosomes are part of promoters and act as UAS/URS of highly conserved COS
      genes.
AB  - A highly conserved 48 bp DNA element was identified present at 26 chromosome ends
      of Saccharomyces cerevisiae. Each element harbours an ideal or a mutated ATF/CREB
      site, which is a well-known target sequence for bZip transcription factors. In
      all cases, the sub-telomeric ATF/CREB site element (SACE) is a direct extension
      of the respective sub-telomeric coreX element. Eight SACEs are part of very long
      quasi-identical regions of several kilobases, including a sub-telomeric COS open
      reading frame. Three of these eight SACEs harbour an ideal ATF/CREB site, four a
      triple-exchange variant (5'-ATGGTATCAT-3'; GTA variant), and one a single
      exchange variant with a C to G exchange at the left side of the center of
      symmetry. We analyzed the function of the SACE of the left arm of chromosome VIII
      in vivo and found its ATF/CREB site to act as UAS/URS of the COS8 promoter,
      effected by the yeast bZip proteins Sko1p, Aca1p, and Aca2p. Cos8 protein was
      found in proximity to the nuclear membrane, where it accumulated, especially
      during cell division. When the ATF/CREB site of the COS8 promoter was exchanged
      with the GTA variant, the regulation was changed. COS8 was then regulated by
      Hac1p, a bZip protein known to be involved in the unfolded protein response of S.
      cerevisiae, indicating, for the first time, a possible functional category for
      the Cos proteins of S. cerevisiae.

PMID- 12051918
TI  - Structural characterization of the reaction pathway in phosphoserine phosphatase:
      crystallographic "snapshots" of intermediate states.
AB  - Phosphoserine phosphatase (PSP) is a member of a large class of enzymes that
      catalyze phosphoester hydrolysis using a phosphoaspartate-enzyme intermediate.
      PSP is a likely regulator of the steady-state d-serine level in the brain, which
      is a critical co-agonist of the N-methyl-d-aspartate type of glutamate receptors.
      Here, we present high-resolution (1.5-1.9 A) structures of PSP from Methanococcus
      jannaschii, which define the open state prior to substrate binding, the complex
      with phosphoserine substrate bound (with a D to N mutation in the active site),
      and the complex with AlF3, a transition-state analog for the phospho-transfer
      steps in the reaction. These structures, together with those described for the
      BeF3- complex (mimicking the phospho-enzyme) and the enzyme with phosphate
      product in the active site, provide a detailed structural picture of the full
      reaction cycle. The structure of the apo state indicates partial unfolding of the
      enzyme to allow substrate binding, with refolding in the presence of substrate to
      provide specificity. Interdomain and active-site conformational changes are
      identified. The structure with the transition state analog bound indicates a
      "tight" intermediate. A striking structure homology, with significant sequence
      conservation, among PSP, P-type ATPases and response regulators suggests that the
      knowledge of the PSP reaction mechanism from the structures determined will
      provide insights into the reaction mechanisms of the other enzymes in this
      family.

PMID- 12051919
TI  - The mechanical hierarchies of fibronectin observed with single-molecule AFM.
AB  - Mechanically induced conformational changes in proteins such as fibronectin are
      thought to regulate the assembly of the extracellular matrix and underlie its
      elasticity and extensibility. Fibronectin contains a region of tandem repeats of
      up to 15 type III domains that play critical roles in cell binding and self
      assembly. Here, we use single-molecule force spectroscopy to examine the
      mechanical properties of fibronectin (FN) and its individual FNIII domains. We
      found that fibronectin is highly extensible due to the unfolding of its FNIII
      domains. We found that the native FNIII region displays strong mechanical
      unfolding hierarchies requiring 80 pN of force to unfold the weakest domain and
      200 pN for the most stable domain. In an effort to determine the identity of the
      weakest/strongest domain, we engineered polyproteins composed of an individual
      domain and measured their mechanical stability by single-protein atomic force
      microscopy (AFM) techniques. In contrast to chemical and thermal measurements of
      stability, we found that the tenth FNIII domain is mechanically the weakest and
      that the first and second FNIII domains are the strongest. Moreover, we found
      that the first FNIII domain can acquire multiple, partially folded conformations,
      and that their incidence is modulated strongly by its neighbor FNIII domain. The
      mechanical hierarchies of fibronectin demonstrated here may be important for the
      activation of fibrillogenesis and matrix assembly.

PMID- 12051920
TI  - Minor structural changes in a mutated human melanoma antigen correspond to
      dramatically enhanced stimulation of a CD4+ tumor-infiltrating lymphocyte line.
AB  - While most immunotherapies for cancer have focused on eliciting specific CD8+
      cytotoxic T lymphocyte killing of tumor cells, a mounting body of evidence
      suggests that stimulation of anti-tumor CD4+ T cell help may be required for
      highly effective therapy. Several MHC class II-restricted tumor antigens that
      specifically activate such CD4+ helper T lymphocytes have now been identified,
      including one from a melanoma tumor that is caused by a single base-pair mutation
      in the glycolytic enzyme triosephosphate isomerase. This mutation results in the
      conversion of a threonine residue to isoleucine within the antigenic epitope,
      concomitant with a greater than five log-fold increase in stimulation of a CD4+
      tumor-infiltrating lymphocyte line. Here, we present the crystal structures of
      HLA-DR1 in complex with both wild-type and mutant TPI peptide antigens, the first
      structures of tumor peptide antigen/MHC class II complexes recognized by CD4+ T
      cells to be reported. These structures show that very minor changes in the
      binding surface for T cell receptor correspond to the dramatic differences in T
      cell stimulation. Defining the structural basis by which CD4+ T cell help is
      invoked in an anti-tumor immune response will likely aid the design of more
      effective cancer immunotherapies.

PMID- 12051921
TI  - Crystal structure of the autocatalytic initiator of glycogen biosynthesis,
      glycogenin.
AB  - Glycogen is an important storage reserve of glucose present in many organisms,
      from bacteria to humans. Its biosynthesis is initiated by a specialized protein,
      glycogenin, which has the unusual property of transferring glucose from UDP
      glucose to form an oligosaccharide covalently attached to itself at Tyr194.
      Glycogen synthase and the branching enzyme complete the synthesis of the
      polysaccharide. The structure of glycogenin was solved in two different crystal
      forms. Tetragonal crystals contained a pentamer of dimers in the asymmetric unit
      arranged in an improper non-crystallographic 10-fold relationship, and
      orthorhombic crystals contained a monomer in the asymmetric unit that is arranged
      about a 2-fold crystallographic axis to form a dimer. The structure was first
      solved to 3.4 A using the tetragonal crystal form and a three-wavelength Se-Met
      multi-wavelength anomalous diffraction (MAD) experiment. Subsequently, an apo
      enzyme structure and a complex between glycogenin and UDP-glucose/Mn2+ were
      solved by molecular replacement to 1.9 A using the orthorhombic crystal form.
      Glycogenin contains a conserved DxD motif and an N-terminal beta-alpha-beta
      Rossmann-like fold that are common to the nucleotide-binding domains of most
      glycosyltransferases. Although sequence identity amongst glycosyltransferases is
      minimal, the overall folds are similar. In all of these enzymes, the DxD motif is
      essential for coordination of the catalytic divalent cation, most commonly Mn2+.
      We propose a mechanism in which the Mn2+ that associates with the UDP-glucose
      molecule functions as a Lewis acid to stabilize the leaving group UDP and to
      facilitate the transfer of the glucose moiety to an intermediate nucleophilic
      acceptor in the enzyme active site, most likely Asp162. Following transient
      transfer to Asp162, the glucose moiety is then delivered to the final acceptor,
      either directly to Tyr194 or to glucose residues already attached to Tyr194. The
      positioning of the bound UDP-glucose far from Tyr194 in the glycogenin structure
      raises questions as to the mechanism for the attachment of the first glucose
      residues. Possibly the initial glucosylation is via inter-dimeric catalysis with
      an intra-molecular mechanism employed later in oligosaccharide synthesis.

PMID- 12051923
TI  - 2.6 A resolution crystal structure of helices of the motile major sperm protein
      (MSP) of Caenorhabditis elegans.
AB  - The amoeboid locomotion of nematode sperm is mediated by the assembly dynamics of
      the major sperm protein (MSP). MSP forms fibrous networks based on a hierarchy of
      macromolecular assemblies: helical subfilaments are built from MSP dimers;
      filaments are formed from two subfilaments coiling round one another; and
      filaments themselves supercoil to produce bundles. To provide a structural
      context for understanding the role of these macromolecular assemblies in cell
      locomotion, we have determined the 2.6 A resolution structure of crystals of
      Caenorhabditis elegans MSP that are constructed from helices of MSP chains that
      are analogous to the subfilaments from which filaments are constructed.
      Comparison with the crystal structures of dimers and helical assemblies of
      Ascaris suum MSP has identified five conserved interaction interfaces that
      suggest how subfilaments interact in filaments and how filaments can form
      bundles. The interfaces frequently involve the loop containing residues 78-85,
      which is divergent between MSP homologues, and the loop containing residues 98
      103, which is highly conserved.

PMID- 12051922
TI  - Crystal structure of aspartate racemase from Pyrococcus horikoshii OT3 and its
      implications for molecular mechanism of PLP-independent racemization.
AB  - There exists a d-enantiomer of aspartic acid in lactic acid bacteria and several
      hyperthermophilic archaea, which is biosynthesized from the l-enantiomer by
      aspartate racemase. Aspartate racemase is a representative pyridoxal 5'-phosphate
      (PLP)-independent amino acid racemase. The "two-base" catalytic mechanism has
      been proposed for this type of racemase, in which a pair of cysteine residues are
      utilized as the conjugated catalytic acid and base. We have determined the three
      dimensional structure of aspartate racemase from the hyperthermophilic archaeum
      Pyrococcus horikoshii OT3 at 1.9 A resolution by X-ray crystallography and
      refined it to a crystallographic R factor of 19.4% (R(free) of 22.2%). This is
      the first structure reported for aspartate racemase, indeed for any amino acid
      racemase from archaea. The crystal structure revealed that this enzyme forms a
      stable dimeric structure with a strong three-layered inter-subunit interaction,
      and that its subunit consists of two structurally homologous alpha/beta domains,
      each containing a four-stranded parallel beta-sheet flanked by six alpha-helices.
      Two strictly conserved cysteine residues (Cys82 and Cys194), which have been
      shown biochemically to act as catalytic acid and base, are located on both sides
      of a cleft between the two domains. The spatial arrangement of these two cysteine
      residues supports the "two-base" mechanism but disproves the previous hypothesis
      that the active site of aspartate racemase is located at the dimeric interface.
      The structure revealed a unique pseudo mirror-symmetry in the spatial arrangement
      of the residues around the active site, which may explain the molecular
      recognition mechanism of the mirror-symmetric aspartate enantiomers by the non
      mirror-symmetric aspartate racemase.

PMID- 12051924
TI  - X-ray structure determination of the cytochrome c2: reaction center electron
      transfer complex from Rhodobacter sphaeroides.
AB  - In the photosynthetic bacterium Rhodobacter sphaeroides, a water soluble
      cytochrome c2 (cyt c2) is the electron donor to the reaction center (RC), the
      membrane-bound pigment-protein complex that is the site of the primary light
      induced electron transfer. To determine the interactions important for docking
      and electron transfer within the transiently bound complex of the two proteins,
      RC and cyt c2 were co-crystallized in two monoclinic crystal forms. Cyt c2
      reduces the photo-oxidized RC donor (D+), a bacteriochlorophyll dimer, in the co
      crystals in approximately 0.9 micros, which is the same time as measured in
      solution. This provides strong evidence that the structure of the complex in the
      region of electron transfer is the same in the crystal and in solution. X-ray
      diffraction data were collected from co-crystals to a maximum resolution of 2.40
      A and refined to an R-factor of 22% (R(free)=26%). The structure shows the cyt c2
      to be positioned at the center of the periplasmic surface of the RC, with the
      heme edge located above the bacteriochlorophyll dimer. The distance between the
      closest atoms of the two cofactors is 8.4 A. The side-chain of Tyr L162 makes van
      der Waals contacts with both cofactors along the shortest intermolecular electron
      transfer pathway. The binding interface can be divided into two domains: (i) A
      short-range interaction domain that includes Tyr L162, and groups exhibiting non
      polar interactions, hydrogen bonding, and a cation-pi interaction. This domain
      contributes to the strength and specificity of cyt c2 binding. (ii) A long-range,
      electrostatic interaction domain that contains solvated complementary charges on
      the RC and cyt c2. This domain, in addition to contributing to the binding, may
      help steer the unbound proteins toward the right conformation.

PMID- 12051925
TI  - Monodisperse Hsp16.3 nonamer exhibits dynamic dissociation and reassociation,
      with the nonamer dissociation prerequisite for chaperone-like activity.
AB  - Small heat-shock proteins (sHsps) of various origins exist commonly as oligomers
      and exhibit chaperone-like activities in vitro. Hsp16.3, the sHsp from
      Mycobacterium tuberculosis, was previously shown to exist as a monodisperse
      nonamer in solution when analyzed by size-exclusion chromatography and electron
      cryomicroscropy. This study represents part of our effort to understand the
      chaperone mechanism of Hsp16.3, focusing on the role of the oligomeric status of
      the protein. Here, we present evidence to show that the Hsp16.3 nonamer
      dissociates at elevated temperatures, accompanied by a greatly enhanced chaperone
      like activity. Moreover, the chaperone-like activity was increased dramatically
      when the nonameric structure of Hsp16.3 was disturbed by chemical cross-linking,
      which impeded the correct reassociation of Hsp16.3 nonamer. These suggest that
      the dissociation of the nonameric structure is a prerequisite for Hsp16.3 to bind
      to denaturing substrate proteins. On the other hand, our data obtained by using
      radiolabeled and non-radiolabeled proteins clearly demonstrated that subunit
      exchange occurs readily between the Hsp16.3 oligomers, even at a temperature as
      low as 4 degrees C. In light of all these observations, we propose that Hsp16.3,
      although it appears to be homogeneous when examined at room temperature, actually
      undertakes rapid dynamic dissociation/reassociation, with the equilibrium, and
      thus the chaperone-like activities, regulated mainly by the environmental
      temperature.

PMID- 12051926
TI  - Prion protein interaction with glycosaminoglycan occurs with the formation of
      oligomeric complexes stabilized by Cu(II) bridges.
AB  - Several lines of evidence have shown glycosaminoglycans (GAGs) to be
      physiological ligands of the prion protein (PrP), but the molecular and
      regulatory aspects of the interaction remain unknown. Using full-length
      recombinant prion protein and low molecular mass heparin and heparan sulfate as
      glycosaminoglycans, we have found that the interaction occurs with the formation
      of oligomeric complexes. Within the protein-glycosaminoglycan complexes, PrP
      exhibited an enhanced fluorescence emission and a reduced solvent exposure. The
      pH and ionic strength-dependence of the interaction reveals His residues as the
      main binding sites at acid pH. A synthetic peptide consisting of four octarepeats
      is able to reproduce the His-dependent binding of the protein, thus demonstrating
      the role of the octarepeats in the GAG interaction. Alternatively, PrP can bind
      GAGs through His-bound Cu(II). These Cu(II) bridges promote a tighter
      interaction, as shown by the increased resistance to ionic strength, to protease
      action, and to pH-induced cation release. Inspection of other cations shows that
      Zn(II) but not Ni(II) shares the interaction trend. Taken together, our data
      suggest that the octarepeat region constitutes a novel GAG-binding sequence and
      that His-bound Cu(II) may act as a cofactor for intermolecular recognition
      reactions, allowing the formation of PrP-Cu(II)-glycosaminoglycan assemblies that
      may be crucial entities in the PrP metabolism.

PMID- 12051927
TI  - The effects of ionic strength on protein stability: the cold shock protein
      family.
AB  - Continuum electrostatic models are used to examine in detail the mechanism of
      protein stabilization and destabilization due to salt near physiological
      concentrations. Three wild-type cold shock proteins taken from mesophilic,
      thermophilic, and hyperthermophilic bacteria are studied using these methods. The
      model is validated by comparison with experimental data collected for these
      proteins. In addition, a number of single point mutants and three designed
      sequences are examined. The results from this study demonstrate that the
      sensitivity of protein stability toward salt is correlated with thermostability
      in the cold shock protein family. The calculations indicate that the mesophile is
      stabilized by the presence of salt while the thermophile and hyperthermophile are
      destabilized. A decomposition of the salt influence at a residue level permits
      identification of regions of the protein sequences that contribute toward the
      observed salt-dependent stability. This model is used to rationalize the effect
      of various point mutations with regard to sensitivity toward salt. Finally, it is
      demonstrated that designed cold shock protein variants exhibit electrostatic
      properties similar to the natural thermophilic and hyperthermophilic proteins.

PMID- 12051928
TI  - Proton translocation by bacteriorhodopsin in the absence of substantial
      conformational changes.
AB  - Unlike wild-type bacteriorhodopsin (BR), the BR triple mutant D96G/F171C/F219L
      has been shown to undergo only minor structural rearrangements during its
      photocycle. Nonetheless, the mutant is capable of transporting protons at a rate
      of 125(+/-40) H+/BR per minute under light-saturating conditions. Light
      adaptation of the triple mutant's retinal proceeds in a pH-dependent manner up to
      a maximum of 63% all-trans. These two findings imply that the transport activity
      of the triple mutant comprises 66% of the wild-type activity. Time-resolved
      spectroscopy reveals that the identity and sequence of intermediates in the
      photocycle of the triple mutant in the all-trans configuration correspond to that
      of wild-type BR. The only differences relate to a slower rise and decay of the M
      and O intermediates, and a significant spectral contribution from a 13-cis
      component. No indication for accumulation of the N intermediate is found under a
      variety of conditions that normally favor the formation of this species in wild
      type BR. The Fourier transform infrared (FTIR) spectrum of the M intermediate in
      the triple mutant resembles that of wild type. Minor changes in the amide I
      region during the photocycle suggest that only small movements of the protein
      backbone occur. Electron microscopy reveals large differences in conformation
      between the unilluminated state of the mutant protein and wild-type but no light
      induced changes in time-resolved measurements. Evidently, proton transport by the
      triple mutant does not require the major conformational rearrangements that occur
      on the same time-scale with wild-type. Thus, we conclude that large
      conformational changes observed in the photocycle of the wild-type and many BR
      mutants are not a prerequisite for the change in accessibility of the Schiff base
      nitrogen atom that must occur during vectorial catalysis to allow proton
      transport.

PMID- 12051929
TI  - Role of conformational fluctuations in the enzymatic reaction of HIV-1 protease.
AB  - The emergence of compensatory drug-resistant mutations in HIV-1 protease
      challenges the common view of the reaction mechanism of this enzyme. Here, we
      address this issue by performing classical and ab initio molecular dynamics
      simulations (MD) on a complex between the enzyme and a peptide substrate. The
      classical MD calculation reveals large-scale protein motions involving the flaps
      and the cantilever. These motions modulate the conformational properties of the
      substrate at the cleavage site. The ab initio calculations show in turn that
      substrate motion modulates the activation free energy barrier of the enzymatic
      reaction dramatically. Thus, the catalytic power of the enzyme does not arise
      from the presence of a pre-organized active site but from the protein mechanical
      fluctuations. The implications of this finding for the emergence of drug
      resistance are discussed.

PMID- 12051931
TI  - Vitamin B12 stalls the 80 S ribosomal complex on the hepatitis C internal
      ribosome entry site.
AB  - The effect of cyanocobalamin (CNCbl, vitamin B12) on hepatitis C virus internal
      ribosome entry site (HCV IRES)-dependent initiation of translation was studied by
      ribosomal toeprinting and sucrose gradient centrifugation analysis. These results
      suggested that CNCbl did not inhibit HCV IRES-dependent translation by a
      competitive binding mechanism. CNCbl allowed 80 S elongation complex formation on
      the mRNA, but stalled the initiation at that point, effectively trapping the 80 S
      ribosomal complexes on the HCV IRES. CNCbl had no effect on cap-dependent mRNA,
      consistent with the known mRNA specificity of this translational inhibitor. To
      help elucidate the mechanism, comparative data were collected for the well
      characterised translation inhibitors cycloheximide and 5'-guanylyl
      imidophosphate. Although CNCbl stalled HCV IRES-dependent translation at
      approximately the same step in initiation as cycloheximide, the mechanisms of
      these two inhibitors are distinct.

PMID- 12051932
TI  - Contrasting IgG structures reveal extreme asymmetry and flexibility.
AB  - The crystal structure of IgG1 b12 represents the first visualization of an intact
      human IgG with a full-length hinge that has all domains ordered and visible. In
      comparison to intact murine antibodies and hinge-deletant human antibodies, b12
      reveals extreme asymmetry, indicative of the extraordinary interdomain
      flexibility within an antibody. In addition, the structure provides an
      illustration of the human IgG1 hinge in its entirety and of asymmetry in the
      composition of the carbohydrate attached to each C(H)2 domain of the Fc. The two
      separate hinges assume different conformations in order to accommodate the vastly
      different placements of the two Fab domains relative to the Fc domain.
      Interestingly, only one of two possible intra-hinge disulfides is formed.

PMID- 12051933
TI  - Measuring dynamic flexibility of the coil state of a helix-forming peptide.
AB  - To investigate the dynamic flexibility of the coil state of a helix-forming
      peptide the end-to-end contact rate was determined. Nanosecond optical excitation
      of tryptophan at one end of a 22 residue, alanine peptide populates a long-lived
      triplet state which is quenched upon close contact with a cyclic disulfide
      attached to the opposite end. Analysis of the decay of the triplet population
      using a two-state model for helix formation yields the diffusion-limited end-to
      end contact rate of the coil state of the peptide as well as the helix-->coil and
      coil-->helix rates. The helix-coil rates are very similar to those previously
      measured in laser temperature-jump experiments. The end-to-end contact rate of
      1.1 x 10(7) s(-1) in the coil state is tenfold faster than the rate for a
      disordered peptide with threonine substituted for alanine and, somewhat
      surprisingly, is about twice the rate for a disordered glycine-containing
      peptide. These differences are discussed in terms of the theory of Szabo,
      Schulten and Schulten. The rates should provide important new benchmarks for
      testing the accuracy of atomistic molecular dynamics simulations.

PMID- 12051934
TI  - Initiation factor IF2, thiostrepton and micrococcin prevent the binding of
      elongation factor G to the Escherichia coli ribosome.
AB  - The bacterial translational GTPases (initiation factor IF2, elongation factors EF
      G and EF-Tu and release factor RF3) are involved in all stages of translation,
      and evidence indicates that they bind to overlapping sites on the ribosome,
      whereupon GTP hydrolysis is triggered. We provide evidence for a common ribosomal
      binding site for EF-G and IF2. IF2 prevents the binding of EF-G to the ribosome,
      as shown by Western blot analysis and fusidic acid-stabilized EF-G.GDP.ribosome
      complex formation. Additionally, IF2 inhibits EF-G-dependent GTP hydrolysis on 70
      S ribosomes. The antibiotics thiostrepton and micrococcin, which bind to part of
      the EF-G binding site and interfere with the function of the factor, also affect
      the function of IF2. While thiostrepton is a strong inhibitor of EF-G-dependent
      GTP hydrolysis, GTP hydrolysis by IF2 is stimulated by the drug. Micrococcin
      stimulates GTP hydrolysis by both factors. We show directly that these drugs act
      by destabilizing the interaction of EF-G with the ribosome, and provide evidence
      that they have similar effects on IF2.

PMID- 12051935
TI  - Effects of substitutions in a conserved DX(2)GR sequence motif, found in many DNA
      dependent nucleotide polymerases, on transcription by T7 RNA polymerase.
AB  - The region in bacteriophage T7 RNA polymerase (RNAP) comprising residues 421-425
      contains a sequence motif (DX(2)GR) that is conserved among many DNA-dependent
      nucleotide polymerases. We have found that alterations in this motif result in
      enzymes that display weaker retention of the RNA product during transcript
      initiation, a decreased ability to make the transition to a stable elongation
      complex, and changes in substrate binding and catalytic activity. Many of these
      defects are coupled with an altered response to the presence or absence of the
      non-template strand. The observed constellation of defects supports a role for
      the motif in interacting with and stabilizing the RNA:DNA hybrid during the early
      stages of transcript initiation. This is consistent with the position of the
      motif in a T7 RNAP initiation complex. Although a conserved DX(2)GR sequence
      motif is also observed in multisubunit RNAPs, the structural organization of the
      motif and the manner in which it interacts with the RNA:DNA hybrid in the latter
      enzymes is different from that in T7 RNAP. However, another element in the
      multisubunit RNAPs that contains a highly conserved arginine residue may play the
      same role as R425 in T7 RNAP. (c) 2002 Elsevier Science Ltd.

PMID- 12051936
TI  - Mechanisms of metal ion action in Tn10 transposition.
AB  - Tn10/IS10 transposition involves assembly of a synaptic complex (or
      transpososome) in which two transposon ends are paired, followed by four distinct
      chemical steps at each transposon end. The chemical steps are dependent on the
      presence of a suitable divalent metal cation (Me(2+)). Transpososome assembly and
      structure are also affected by Me(2+). To gain further insight into the
      mechanisms of Me(2+) action in Tn10/IS10 transposition we have investigated the
      effects of substituting Mn(2+) for Mg(2+), the physiologic Me(2+), in
      transposition. We have also investigated the significance of an Me(2+)-assisted
      conformational change in transpososome structure. We show that Mn(2+) has two
      previously unrecognized effects on the Tn10 donor cleavage reaction. It
      accelerates the rates of hairpin formation and hairpin resolution without
      significantly affecting the rate of the first chemical step, first strand
      nicking. Mn(2+) also relaxes the specificity of first strand nicking. We also
      show that Me(2+)-assisted transpososome unfolding coincides with a structural
      transition in the transposon-donor junction that may be necessary for hairpin
      formation. Possible mechanisms for these observations are considered.

PMID- 12051937
TI  - Cation-pi/H-bond stair motifs at protein-DNA interfaces.
AB  - H-bonds and cation-pi interactions between nucleic acid bases and amino acid side
      chains are known to occur often concomitantly at the interface between protein
      and double-stranded DNA. Here we define and analyze stair-shaped motifs, which
      simultaneously involve base stacking, H-bond and cation-pi interactions. They
      consist of two successive bases along the DNA stack, one in cation-pi interaction
      with an amino acid side-chain that carries a total or partial positive charge,
      and the other H-bonded with the same side-chain. A survey of 52 high-resolution
      structures of protein/DNA complexes reveals the occurrence of such motifs in the
      majority of the complexes, the most frequent of these motifs involving Arg side
      chains and G bases. These stair motifs are sometimes part of larger motifs,
      called multiple stair motifs, which contain several successive stairs; zinc
      finger proteins for example exhibit up to quadruple stairs. In another kind of
      stair motif extension, termed cation-pi chain motif, an amino acid side-chain or
      a nucleic acid base forms simultaneously two cation-pi interactions. Such a motif
      is observed in several homeodomains, where it involves a DNA base in cation-pi
      interactions with an Arg in the minor groove and an Asn in the major groove. A
      different cation-pi chain motif contains an Arg in cation-pi with a G and a Tyr,
      and is found in ets transcription factors. Still another chain motif is
      encountered in proteins that expulse a base from the DNA stack and replace it by
      an amino acid side-chain carrying a net or partial positive charge, which forms
      cation-pi interactions with the two neighboring bases along the DNA strand. The
      striking conservation of typical stair and cation-pi chain motifs within families
      of protein/DNA complexes suggests that they might play a structural and/or
      functional role and might moreover influence electron migration through the DNA
      double helix.

PMID- 12051938
TI  - Quantification of the influence of HPrSer46P on CcpA-cre interaction.
AB  - Carbon catabolite repression (CCR) of the Bacillus megateriumxyl operon is
      dependent on the catabolite responsive element cre, the catabolite control
      protein (CcpA) and the histidine-containing phosphocarrier protein phosphorylated
      at the serine 46 residue (HPrSer46P). The latter is formed in the presence of
      glucose and mediates CCR via CcpA. We present evidence for the presence of
      HPrSer46P in a ternary complex with CcpA and cre. We also demonstrate increased
      stability of this complex compared to the CcpA-cre complex by electrophoretic
      mobility shift analysis (EMSA). This stabilization by HPrSer46P is the same for
      the xyl cre and an improved cre. Thus, HPrSer46P is a co-repressor for CcpA. In
      addition, surface plasmon resonance (SPR) experiments yielded binding constants
      of CcpA and the CcpA-HPrSer46P complex with cre. HPrSer46P stimulated CcpA
      binding to cre 50-fold. The binding constant is 4.9(+/- 0.5) x 10(6) M(-1). Non
      phosphorylated HPr did not affect the complex formation between CcpA and cre.
      Previously proposed effects by glucose-6-phosphate, fructose-1,6-diphosphate and
      NADP on CcpA-cre or CcpA-HPrSer46P-cre formation were not found in EMSA and SPR
      experiments.

PMID- 12051939
TI  - Metal-dependent folding and stability of nuclear hormone receptor DNA-binding
      domains.
AB  - The nuclear/hormone receptors are an extensive family of ligand-activated
      transcription factors that recognise DNA targets through a highly conserved,
      structurally autonomous DNA-binding domain. The compact structure of the DNA
      binding domain is supported by two zinc ions, each of which is co-ordinated by
      the tetrahedral arrangement of thiol groups from four cysteine residues. Metal
      binding is expected to be linked with deprotonation of the co-ordinating thiol
      groups and folding of the polypeptide. Using a variety of biophysical approaches,
      we characterise these linked equilibria for the isolated DNA-binding domains
      (DBD) of the receptors for estrogen and glucocorticoid. Mass spectrometry and
      equilibrium denaturation indicate that, near neutral pH, approximately four of
      the eight co-ordinating thiol groups release protons with zinc uptake, in
      agreement with the expected pK(a) change for the -SH group in the presence of the
      metal. Mass spectrometry reveals that the protein charge distribution changes
      with the uptake of zinc and that metal binding is co-operative. The co
      operativity is consistent with observations from equilibrium denaturation, which
      indicate that the folding event is a two-state process. A crucial residue that
      stabilises the equilibrium structure of the DBD fold itself is a cysteine residue
      situated in the hydrophobic core of all known nuclear hormone receptors (but not
      involved in metal binding): it appears to be conserved absolutely for its unique
      combination of size and hydrophobicity. Stabilisation of the DBDs could be
      achieved by truncating the flexible, basic termini, suggesting that like-charge
      clusters may have deleterious effects on protein folds. While the metal-free apo
      protein and the chemically denatured state have little defined secondary
      structure, these states were expanded only partially in comparison with the
      native structure, according to data from small-angle X-ray scattering. The
      comparatively compact shapes of the denatured and apo forms may explain, in part,
      the marginal stability of the native fold.

PMID- 12051940
TI  - The order of strand exchanges in Cre-LoxP recombination and its basis suggested
      by the crystal structure of a Cre-LoxP Holliday junction complex.
AB  - Cre recombinase uses two pairs of sequential cleavage and religation reactions to
      exchange homologous DNA strands between 34 base-pair (bp) LoxP recognition
      sequences. In the oligomeric recombination complex, a switch between "cleaving"
      and "non-cleaving" subunit conformations regulates the number, order, and regio
      specificity of the strand exchanges. However, the particular sequence of events
      has been in question. From analysis of strand composition of the Holliday
      junction (HJ) intermediate, we determined that Cre initiates recombination of
      LoxP by cleaving the upper strand on the left arm. Cre preferred to react with
      the left arm of a LoxP suicide substrate, but at a similar rate to the right arm,
      indicating that the first strand to be exchanged is selected prior to cleavage.
      We propose that during complex assembly the cleaving subunit preferentially
      associates with the LoxP left arm, directing the first strand exchange to that
      side. In addition, this biased assembly would enforce productive orientation of
      LoxP sites in the recombination synapses. A novel Cre-HJ complex structure in
      which LoxP was oriented with the left arm bound by the cleaving Cre subunit
      suggested a physical basis for the strand exchange order. Lys86 and Lys201
      interact with the left arm scissile adenine base differently than in structures
      that have a scissile guanine. These interactions are associated with positioning
      the 198-208 loop, a structural component of the conformational switch, in a
      configuration that is specific to the cleaving conformation. Our results suggest
      that strand exchange order and site alignment are regulated by an "induced fit"
      mechanism in which the cleaving conformation is selectively stabilized through
      protein-DNA interactions with the scissile base on the strand that is cleaved
      first.

PMID- 12051942
TI  - Free energy and structural pathways of base flipping in a DNA GCGC containing
      sequence.
AB  - Structural distortions of DNA are essential for its biological function due to
      the genetic information of DNA not being physically accessible in the duplex
      state. Base flipping is one of the simplest structural distortions of DNA and may
      represent an initial event in strand separation required to access the genetic
      code. Flipping is also utilized by DNA-modifying and repair enzymes to access
      specific bases. It is typically thought that base flipping (or base-pair opening)
      occurs via the major groove whereas minor groove flipping is only possible when
      mediated by DNA-binding proteins. Here, umbrella sampling with a novel center-of
      mass pseudodihedral reaction coordinate was used to calculate the individual
      potentials of mean force (PMF) for flipping of the Watson-Crick (WC) paired C and
      G bases in the CCATGCGCTGAC DNA dodecamer. The novel reaction coordinate allowed
      explicit investigation of the complete flipping process via both the minor and
      major groove pathways. The minor and major groove barriers to flipping are
      similar for C base flipping while the major groove barrier is slightly lower for
      G base flipping. Minor groove flipping requires distortion of the WC partner
      while the flipping base pulls away from its partner during major groove flipping.
      The flipped states are represented by relatively flat free energy surfaces, with
      a small, local minimum observed for the flipped G base. Conserved patterns of
      phosphodiester backbone dihedral distortions during flipping indicate their
      essential role in the flipping process. During flipping, the target base tracks
      along the respective grooves, leading to hydrogen-bonding interactions with
      neighboring base-pairs. Such hydrogen-bonding interactions with the neighboring
      sequence suggest a novel mechanism of sequence dependence in DNA dynamics.

PMID- 12051941
TI  - Role of tryptophan residues in the recognition of mutagenic oxidized nucleotides
      by human antimutator MTH1 protein.
AB  - The human MTH1 antimutator protein hydrolyzes mutagenic oxidized nucleotides, and
      thus prevents their incorporation into DNA and any subsequent mutation. We have
      examined its great selectivity for oxidized nucleotides by analyzing the
      structure of the protein and its interaction with nucleotides, as reflected in
      the fluorescence of its tryptophan residues. The binding of nucleotides decreased
      the intensity of MTH1 protein fluorescence and red-shifted the emission peak,
      indicating that at least one tryptophan residue is close to the binding site.
      Oxidized nucleotides (2-OH-dATP and 8-oxo-dGTP) produced a larger decrease in
      fluorescence intensity than did unoxidized nucleotides, and MTH1 protein had a
      much higher binding affinity for oxidized nucleotides. Deconvolution of protein
      fluorescence by comparison of its quenching by positively (Cs(+)) and negatively
      (I(-)) charged ions indicated that the MTH1 tryptophan residues are in two
      different environments. One class of tryptophan residues is exposed to solvent
      but in a negatively charged environment; the other class is partially buried.
      While the binding of unoxidized nucleotides quenches the fluorescence of only
      class 1 tryptophan residue(s), the binding of oxidized nucleotides quenched that
      of class 2 tryptophan residue(s) as well. This suggests that selectivity is due
      to additional contact between the protein and the oxidized nucleotide. Mutation
      analysis indicated that the tryptophan residue at position 117, which is in a
      negative environment, is in contact with nucleotides. The negatively charged
      residues in the binding site probably correlate with the finding that nucleotide
      binding requires metal ions and depends upon their nature. Positively charged
      metal ions probably act by neutralizing the negatively charged nucleotide
      phosphate groups. (c) 2002 Elsevier Science Ltd.

PMID- 12051943
TI  - Crystal structure of decameric fructose-6-phosphate aldolase from Escherichia
      coli reveals inter-subunit helix swapping as a structural basis for assembly
      differences in the transaldolase family.
AB  - Fructose-6-phosphate aldolase from Escherichia coli is a member of a small enzyme
      subfamily (MipB/TalC family) that belongs to the class I aldolases. The three
      dimensional structure of this enzyme has been determined at 1.93 A resolution by
      single isomorphous replacement and tenfold non-crystallographic symmetry
      averaging and refined to an R-factor of 19.9% (R(free) 21.3%). The subunit folds
      into an alpha/beta barrel, with the catalytic lysine residue on barrel strand
      beta 4. It is very similar in overall structure to that of bacterial and
      mammalian transaldolases, although more compact due to extensive deletions of
      additional secondary structural elements. The enzyme forms a decamer of identical
      subunits with point group symmetry 52. Five subunits are arranged as a pentamer,
      and two ring-like pentamers pack like a doughnut to form the decamer. A major
      interaction within the pentamer is through the C-terminal helix from one monomer,
      which runs across the active site of the neighbouring subunit. In classical
      transaldolases, this helix folds back and covers the active site of the same
      subunit and is involved in dimer formation. The inter-subunit helix swapping
      appears to be a major determinant for the formation of pentamers rather than
      dimers while at the same time preserving importing interactions of this helix
      with the active site of the enzyme. The active site lysine residue is covalently
      modified, by forming a carbinolamine with glyceraldehyde from the crystallisation
      mixture. The catalytic machinery is very similar to that of transaldolase, which
      together with the overall structural similarity suggests that enzymes of the
      MipB/TALC subfamily are evolutionary related to the transaldolase family.

PMID- 12051944
TI  - Crystal structure of human MMP9 in complex with a reverse hydroxamate inhibitor.
AB  - Matrix metalloproteinases (MMPs) and their inhibitors are important in connective
      tissue re-modelling in diseases of the cardiovascular system, such as
      atherosclerosis. Various members of the MMP family have been shown to be
      expressed in atherosclerotic lesions, but MMP9 is consistently seen in
      inflammatory atherosclerotic lesions. MMP9 over-expression is implicated in the
      vascular re-modelling events preceding plaque rupture (the most common cause of
      acute myocardial infarction). Reduced MMP9 activity, either by genetic
      manipulation or through pharmacological intervention, has an impact on
      ventricular re-modelling following infarction. MMP9 activity may therefore
      represent a key mechanism in the pathogenesis of heart failure. We have
      determined the crystal structure, at 2.3 A resolution, of the catalytic domain of
      human MMP9 bound to a peptidic reverse hydroxamate inhibitor as well as the
      complex of the same inhibitor bound to an active-site mutant (E402Q) at 2.1 A
      resolution. MMP9 adopts the typical MMP fold. The catalytic centre is composed of
      the active-site zinc ion, co-ordinated by three histidine residues (401, 405 and
      411) and the essential glutamic acid residue (402). The main differences between
      the catalytic domains of various MMPs occur in the S1' subsite or selectivity
      pocket. The S1' specificity site in MMP9 is perhaps best described as a tunnel
      leading toward solvent, as in MMP2 and MMP13, as opposed to the smaller pocket
      found in fibroblast collagenase and matrilysin. The present structure enables us
      to aid the design of potent and specific inhibitors for this important
      cardiovascular disease target.

PMID- 12051945
TI  - On the role of the conformational flexibility of the active-site lid on the
      allosteric kinetics of glucosamine-6-phosphate deaminase.
AB  - The active site of glucosamine-6-phosphate deaminase from Escherichia coli
      (GlcN6P deaminase, EC 3.5.99.6) has a complex lid formed by two antiparallel beta
      strands connected by a helix-loop segment (158-187). This motif contains Arg172,
      which is a residue involved in binding the substrate in the active-site, and
      three residues that are part of the allosteric site, Arg158, Lys160 and Thr161.
      This dual binding role of the motif forming the lid suggests that it plays a key
      role in the functional coupling between active and allosteric sites. Previous
      crystallographic work showed that the temperature coefficients of the active-site
      lid are very large when the enzyme is in its T allosteric state. These
      coefficients decrease in the R state, thus suggesting that this motif changes its
      conformational flexibility as a consequence of the allosteric transition. In
      order to explore the possible connection between the conformational flexibility
      of the lid and the function of the deaminase, we constructed the site-directed
      mutant Phe174-Ala. Phe174 is located at the C-end of the lid helix and its side
      chain establishes hydrophobic interactions with the remainder of the enzyme. The
      crystallographic structure of the T state of Phe174-Ala deaminase, determined at
      2.02 A resolution, shows no density for the segment 162-181, which is part of the
      active-site lid (PDB 1JT9). This mutant form of the enzyme is essentially
      inactive in the absence of the allosteric activator, N-acetylglucosamine-6-P
      although it recovers its activity up to the wild-type level in the presence of
      this ligand. Spectrometric and binding studies show that inactivity is due to the
      inability of the active-site to bind ligands when the allosteric site is empty.
      These data indicate that the conformational flexibility of the active-site lid
      critically alters the binding properties of the active site, and that the
      occupation of the allosteric site restores the lid conformational flexibility to
      a functional state.

PMID- 12051946
TI  - Structural differences in the NOE-derived structure of G-T mismatched DNA
      relative to normal DNA are correlated with differences in (13)C relaxation-based
      internal dynamics.
AB  - Detailed description of the characteristics of mismatched DNA that are distinct
      from normal DNA is vital to the understanding of how mismatch repair proteins are
      able to recognize and repair these DNA lesions. To this end, we have used nuclear
      Overhauser effect spectroscopy (NOESY)-based distance restraints and (13)C
      relaxation measurements to solve the solution structures and measure some of the
      internal dynamics of the G-T mismatched DNA oligomer d(CCATGCGTGG)(2) (GT) and
      its parent DNA sequence d(CCACGCGTGG)(2) (GC). In GT, the mismatched G7 is
      structurally perturbed much more than the mismatched T4 relative to their
      corresponding bases in GC. The degree of G7 displacement differs from previous
      high-resolution structures of G-T mismatch-containing B-DNA, suggesting a
      dependence of G-T mismatch-induced structural perturbation on sequence context.
      The internal dynamics of GC and GT differ on multiple timescales. The mismatched
      G7 of GT contains spins that decrease significantly in order in GT compared to
      GC, while spins in C6, T8, and A3 have significantly higher order in GT compared
      to GC. Linear correlations between helical parameters of GC and GT and the order
      of C-1' and aromatic methine carbon atoms relate differences in internal dynamics
      to the structures quantitatively. The dynamic differences between the normal and
      mismatched DNA signify changes in local flexibility that may be exploited by the
      mismatch repair system to bind mismatched DNA preferentially while ignoring
      normal DNA.

PMID- 12051947
TI  - Protein NMR structure determination with automated NOE assignment using the new
      software CANDID and the torsion angle dynamics algorithm DYANA.
AB  - Combined automated NOE assignment and structure determination module (CANDID) is
      a new software for efficient NMR structure determination of proteins by automated
      assignment of the NOESY spectra. CANDID uses an iterative approach with multiple
      cycles of NOE cross-peak assignment and protein structure calculation using the
      fast DYANA torsion angle dynamics algorithm, so that the result from each CANDID
      cycle consists of exhaustive, possibly ambiguous NOE cross-peak assignments in
      all available spectra and a three-dimensional protein structure represented by a
      bundle of conformers. The input for the first CANDID cycle consists of the amino
      acid sequence, the chemical shift list from the sequence-specific resonance
      assignment, and listings of the cross-peak positions and volumes in one or
      several two, three or four-dimensional NOESY spectra. The input for the second
      and subsequent CANDID cycles contains the three-dimensional protein structure
      from the previous cycle, in addition to the complete input used for the first
      cycle. CANDID includes two new elements that make it robust with respect to the
      presence of artifacts in the input data, i.e. network-anchoring and constraint
      combination, which have a key role in de novo protein structure determinations
      for the successful generation of the correct polypeptide fold by the first CANDID
      cycle. Network-anchoring makes use of the fact that any network of correct NOE
      cross-peak assignments forms a self-consistent set; the initial, chemical shift
      based assignments for each individual NOE cross-peak are therefore weighted by
      the extent to which they can be embedded into the network formed by all other NOE
      cross-peak assignments. Constraint-combination reduces the deleterious impact of
      artifact NOE upper distance constraints in the input for a protein structure
      calculation by combining the assignments for two or several peaks into a single
      upper limit distance constraint, which lowers the probability that the presence
      of an artifact peak will influence the outcome of the structure calculation.
      CANDID test calculations were performed with NMR data sets of four proteins for
      which high-quality structures had previously been solved by interactive
      protocols, and they yielded comparable results to these reference structure
      determinations with regard to both the residual constraint violations, and the
      precision and accuracy of the atomic coordinates. The CANDID approach has further
      been validated by de novo NMR structure determinations of four additional
      proteins. The experience gained in these calculations shows that once nearly
      complete sequence-specific resonance assignments are available, the automated
      CANDID approach results in greatly enhanced efficiency of the NOESY spectral
      analysis. The fact that the correct fold is obtained in cycle 1 of a de novo
      structure calculation is the single most important advance achieved with CANDID,
      when compared with previously proposed automated NOESY assignment methods that do
      not use network-anchoring and constraint-combination.

PMID- 12051948
TI  - Probing the energy landscape of protein folding/unfolding transition states.
AB  - Previous molecular dynamics (MD) simulations of the thermal denaturation of
      chymotrypsin inhibitor 2 (CI2) have provided atomic-resolution models of the
      transition state ensemble that is well supported by experimental studies. Here,
      we use simulations to further investigate the energy landscape around the
      transition state region. Nine structures within approximately 35 ps and 3 A
      C(alpha) RMSD of the transition state ensemble identified in a previous 498 K
      thermal denaturation simulation were quenched under the quasi-native conditions
      of 335 K and neutral pH. All of the structures underwent hydrophobically driven
      collapse in response to the drop in temperature. Structures less denatured than
      the transition state became structurally more native-like, while structures that
      were more denatured than the transition state tended to show additional loss of
      native structure. The structures in the immediate region of the transition state
      fluctuated between becoming more and less native-like. All of the starting
      structures had the same native-like topology and were quite similar (within 3.5 A
      C(alpha) RMSD). That the structures all shared native-like topology, yet diverged
      into either more or less native-like structures depending on which side of the
      transition state they occupied on the unfolding trajectory, indicates that
      topology alone does not dictate protein folding. Instead, our results suggest
      that a detailed interplay of packing interactions and interactions with water
      determine whether a partially denatured protein will become more native-like
      under refolding conditions.

PMID- 12051949
TI  - A hierarchic approach to the design of hexameric helical barrels.
AB  - The design of large macromolecular assemblies is an endeavor with implications
      for protein engineering as well as nanotechnology. A hierarchic approach was used
      to design an antiparallel hexameric, tubular assembly of helices. In previous
      studies, a domain-swapped, dimeric three-helix bundle was designed from first
      principles. In the crystal lattice, three dimers associate around a 3-fold
      rotational axis to form a hexameric assembly. Although this hexameric assembly
      was not observed in solution, it was possible to stabilize its formation by
      changing three polar residues per monomer to hydrophobic (two Phe and one Trp)
      residues. Molecular models based on the crystallographic coordinates of DSD (PDB
      accession code 1G6U) show that these side-chains pack in the central cavity (the
      "supercore") of the hexameric bundle. Analytical ultracentrifugation,
      fluorescence spectroscopy, CD spectroscopy, and guanidine-HCl denaturation were
      used to determine the assembly of the hexamer. To probe the requirements for
      stabilizing the hexamer, we systematically varied the polarity and steric bulk of
      one of the Phe residues in the supercore of the hexamer. Depending on the nature
      of this side-chain, it is possible to modulate the stability of the hexamer in a
      predictable manner. This family of hexameric proteins may provide a useful
      framework for the construction of proteins that change their oligomeric states in
      response to binding of small molecules.

PMID- 12051951
TI  - Antitumour actions of highly unsaturated fatty acids: cell signalling and
      apoptosis.

PMID- 12051952
TI  - Antineoplastic properties of arachidonic acid and its metabolites.

PMID- 12051953
TI  - Characterization of cyclooxygenase-2 (COX-2) during tumorigenesis in human
      epithelial cancers: evidence for potential clinical utility of COX-2 inhibitors
      in epithelial cancers.
AB  - Increased prostaglandins (PGs) are associated with many inflammatory
      pathophysiological conditions; and are synthesized from arachidonic acid by
      either of 2 enzymes, cyclooxygenase-1 (COX-1) or -2 (COX-2). Recent
      epidemiologic, expression, and pharmacologic studies suggest COX-2 derived
      metabolites also play a functional role in the maintenance of tumor viability,
      growth and metastasis. Archival and/or prospectively collected human tissues were
      prepared for immunohistochemistry, and representative cases assayed via Western
      blot, RT-PCR, or TAQman analysis. Consistent overexpression of COX-2 was observed
      in a broad range of premalignant, malignant, and metastatic human epithelial
      cancers. COX-2 was detected in ca. 85% of the hyperproliferating, dysplastic, and
      neoplastic epithelial cells, and in the existing and angiogenic vasculature
      within and adjacent to hyperplastic/neoplastic lesions. These data collectively
      imply COX-2 may play an important role during premalignant hyperproliferation, as
      well as the later stages of invasive carcinoma and metastasis in various human
      epithelial cancers.

PMID- 12051954
TI  - Antitumour and pro-apoptotic actions of highly unsaturated fatty acids in glioma.
AB  - The highly unsaturated fatty acids (HUFA) of the n-6 and n-3 series are involved
      in cell signalling in normal and transformed cells and have recently been
      associated with pathways leading to tumour cell death. The antitumour activity of
      three HUFA (arachidonic acid, gamma linolenic acid and eicosapentaenoic acid)
      were studied in glioma cells and tissue. Using five glioma models, including
      primary cell suspensions prepared from 46 human glioma samples and an in vivo rat
      C6 glioma model, we obtained evidence that, following exposure to HUFA, either
      administered into the medium surrounding human glioma cells or in 16 preparations
      of multicellular spheroids derived from human and rodent glioma cell lines (C6,
      MOG, U87, U373) or administered intra-tumourally by infusion using osmotic mini
      pumps in 48 rats, glioma regression and apoptosis were detected. Additionally,
      synergy between gamma irradiation and HUFA administration was observed in 13
      experiments analyzing C6 glioma cell apoptosis in vitro. These pro-apoptotic and
      antiproliferative activities were observed using both C18 and C20 fatty acids of
      the n-6 and n-3 series, but not when saturated and monounsaturated C18 and C20
      fatty acid preparations were used. In the glioma infusion model, in addition to
      the apoptosis detected in glioma tissue infused with HUFA for 3-7 days,
      preservation of normal neural tissue and vasculature in adjacent brain was
      observed. Also, there was little evidence of acute inflammatory infiltration in
      regressing tumours. Our findings suggest that intraparenchymal infusion of HUFA
      may be effective in stimulating glioma regression.

PMID- 12051955
TI  - Specificity of arachidonic acid-induced inhibition of growth and activation of c
      jun kinases and p38 mitogen-activated protein kinase in hematopoietic cells.
AB  - We demonstrated that arachidonic acid inhibits growth and induces apoptosis in
      the bcr-abl transformed leukemia cell line, H7.bcr-abl A54 and in human chronic
      myeloid leukemia hematopoietic cells. This investigation was undertaken to
      determine the cell-type specificity of this response. We compared the effect of
      arachidonic acid on H7.bcr-abl A54 cells to Jurkat (human acute T-cell leukemia),
      U937 (human histiocytic lymphoma) and RPMI 7666 (human normal B-lymphoblasts)
      cells. Arachidonic acid (100 microM, 72 h) inhibited growth of H7.bcr-abl A54,
      Jurkat and U937 cells by 82.2, 67.5 and 20%, respectively, but had no effect on
      RPMI 7666 cells. These effects were investigated in relationship to the
      activation of p38 mitogen activated protein kinase (p38 MAPK) and c-jun amino
      terminal kinase (JNK) by arachidonic acid in these cell lines. Results from these
      studies suggest that signaling and proliferative responses to arachidonic acid
      are cell-type specific. Leukemia cells appear to be more sensitive to the
      antiproliferative effect of arachidonic acid than normal cells.

PMID- 12051956
TI  - Signaling and proapoptotic functions of transformed cell-derived reactive oxygen
      species.
AB  - Transformed fibroblasts generate extracellular superoxide anions through the
      recently identified membrane-associated NADPH oxidase. These cell-derived
      superoxide anions exhibit signaling functions such as regulation of proliferation
      and maintenance of the transformed state. Their dismutation product hydrogen
      peroxide regulates the intracellular level of catalase, whose activity has been
      observed to be upregulated in certain transformed cells. After glutathione
      depletion, transformed cell-derived reactive oxygen species (ROS) exhibit
      apoptosis-inducing potential through the metal-catalyzed Haber-Weiss reaction.
      Moreover, transformed cell-derived ROS represent key elements for selective and
      efficient apoptosis induction by natural antitumor systems (such as fibroblasts,
      granulocytes and macrophages). These effector cells release peroxidase, which
      utilizes target cell-derived hydrogen peroxide for HOCl synthesis. In a second
      step, HOCl interacts with target cell-derived superoxide anions and forms
      apoptosis-inducing hydroxyl radicals. In a parallel signaling pathway, effector
      cell-derived NO interacts with target cell-derived superoxide anions and
      generates the apoptosis inducer peroxynitrite. Therefore, transformed cell
      derived ROS determine transformed cells as selective targets for induction of
      apoptosis by these effector systems. It is therefore proposed that transformed
      cell derived ROS interact with associated cells to exhibit directed and specific
      signaling functions, some of which are beneficial and some of which can become
      detrimental to transformed cells.

PMID- 12051957
TI  - The role of arachidonic acid in normal and malignant hematopoiesis.

PMID- 12051958
TI  - PGE(2) receptors and synthesis in human gastric mucosa: perturbation in cancer.
AB  - Recent evidence suggests that prostanoids are an important participant in the
      pathobiology of gastric adenocarcinoma, but the location and identity of cells in
      tumor-adjacent gastric mucosa able to synthesize and/or bind specific prostanoids
      is not clear. Using probes for cyclooxygenase 1 and 2 mRNA and protein as well as
      for the EP family of PGE(2) receptors, we sought to define the biology of
      prostanoids in adjacent human gastric mucosa at the site of tumor invasion. In
      mucosa adjacent to an invasive gastric adenocarcinoma, expression of
      cyclooxygenase was prominent, with COX 1 primarily in mucosal T lymphocytes
      surrounding nests of tumor cells. Densitometry showed these tumor-adjacent cells
      had substantial levels of COX 1 immunoreactive protein (relative intensity, 3.2).
      Cyclooxygenase 2 was newly expressed among these cells as well, but was limited
      in number (<25% of cyclooxygenase-positive T lymphocytes) in tumor-adjacent
      mucosa. Further, CD3(+) mononuclear cells, adjacent to tumor, strongly expressed
      prostanoid receptor EP(4) (relative intensity, 8.0), but cells with this receptor
      were not evident in the tumor itself. In contrast, normal gastric mucosa showed a
      consistent and structured expression of cyclooxygenase and PGE(2) receptor
      immunoreactive protein among mucosal cells. Cyclooxygenase 1 and PGE(2) receptor
      EP(4) were expressed on mucosal CD3(+) T lymphocytes in the lumenal (upper) third
      of gastric mucosa; and prostanoid receptors EP(2), EP(3) and EP(4), on gastric
      epithelia lining gastric pits. In situ hybridization with COX cDNAs confirmed
      these findings, and neither COX 2-specific mRNA nor protein was detected in
      normal gastric tissue. Our studies suggest that synthetic machinery and receptors
      for PGE(2), prominently expressed by T lymphocytes in gastric mucosa at the
      boundary of normal mucosa with tumor cells, may play a central role in prostanoid
      driven tumorigenesis of this tissue.

PMID- 12051960
TI  - The NH(2)-terminal and carboxyl-terminal interaction in the human androgen
      receptor.

PMID- 12051959
TI  - Eicosapentaenoic acid and arachidonic acid: collaboration and not antagonism is
      the key to biological understanding.
AB  - Much of the literature on omega-3 and omega-6 fatty acids suggests that desirable
      effects of omega-3 fatty acids are in part related to depletion of arachidonic
      acid (AA). However, in rats and humans, we have found that low doses of EPA
      actually elevate membrane AA phospholipid concentrations. In patients with
      schizophrenia, treatment with eicosapentaenoic acid (EPA) produced clinical
      improvement, but that improvement was greater at a dose of 2 g/day than at 4
      g/day. The improvement was not significantly correlated with changes in either
      EPA or docosahexaenoic acid (DHA) but was highly significantly positively
      correlated with rises in red cell membrane AA. We suggest that elevation of
      concentrations of both AA and EPA in cell membranes may be important for health.

PMID- 12051961
TI  - Newborn screening as a model for population screening.

PMID- 12051962
TI  - Compound heterozygous mutations in KvLQT1 cause Jervell and Lange-Nielsen
      syndrome.
AB  - Jervell and Lange-Nielsen syndrome (JLNS) is characterized by sensorineural
      deafness, QT prolongation, abnormal T waves, ventricular tachyarrhythmias, and
      autosomal recessive inheritance. Previously homozygous mutations in the potassium
      channel-encoding genes, KvLQT1 (alpha-subunit) and KCNE1 (beta-subunit), have
      been described in consanguineous families with JLNS. We screened two
      nonconsanguineous families with JLNS for mutations in KvLQT1, using single-strand
      conformation polymorphism analysis, denaturing high-performance liquid
      chromatography, and DNA sequencing. In one family, a missense mutation was
      identified in exon 6 of KvLQT1 on the maternal side, resulting in a glycine to
      aspartic acid substitution at codon 269 (G269D). The apparently normal father had
      an incompletely penetrant missense mutation in exon 3 of KvLQT1, introducing a
      premature stop codon at position 171. In the other family, a missense mutation
      resulting in the substitution of asparagine for aspartic acid at codon 202
      (D202N) was identified in the mother and maternal grandmother, who had QTc
      prolongation (borderline in the mother), while the father and paternal
      grandfather, who were clinically normal, had a deletion of nucleotide 585,
      resulting in a frameshift and premature termination. In both families, the
      proband inherited both mutations. In this report we provide evidence that not
      only homozygous but also compound heterozygous mutations in KvLQT1 may cause JLNS
      in nonconsanguineous families. Incomplete penetrance in individuals with
      mutations appears to be frequent, indicating a higher prevalence of mutations
      than estimated previously. Interestingly, mutations resulting in truncation of
      the protein appear to be benign, with heterozygous carriers being asymptomatic.

PMID- 12051964
TI  - Cholesterol storage defect in RSH/Smith-Lemli-Opitz syndrome fibroblasts.
AB  - The RSH/Smith-Lemli-Opitz syndrome (SLOS) is a multiple malformation/mental
      retardation syndrome caused by an inborn error of cholesterol synthesis.
      Mutations in the 3beta-hydroxysteroid Delta(7)-reductase gene result in impaired
      enzymatic reduction of 7-dehydrocholesterol (7-DHC) to cholesterol. Cells obtain
      cholesterol by either de novo synthesis or from exogenous sources by the binding
      and uptake of low density lipoprotein (LDL) particles. Because de novo synthesis
      of cholesterol is impaired in SLOS, current investigational therapy for SLOS
      consists of dietary cholesterol supplementation. However, the potential effects
      of elevated intracellular levels of 7-DHC on intracellular LDL metabolism have
      not been described. We now report that in addition to the primary defect in de
      novo cholesterol synthesis, SLOS fibroblasts have a secondary defect of LDL
      cholesterol metabolism. Staining of fibroblasts with filipin, a fluorescent
      polyene antibiotic which binds unesterified sterols, shows that SLOS fibroblasts
      accumulate unesterified sterols. Further studies show that this increased filipin
      staining was due to an abnormal accumulation of LDL derived cholesterol rather
      than due to storage of endogenously synthesized 7-dehydrocholesterol (7-DHC). We
      have also found that SLOS fibroblasts failed to degrade LDL at a normal rate, and
      examination of SLOS fibroblasts by electron microscopy demonstrated the formation
      of lysosomal inclusions similar to that seen in Niemann-Pick type C (NPC) cells.
      We propose that 7-DHC may directly or indirectly inhibit the function of the NPC
      protein through its sterol-sensing domain (SSD), and that 7-DHC may perturb the
      function of other SSD containing proteins in SLOS.

PMID- 12051963
TI  - Novel mutations in domain I of SCN5A cause Brugada syndrome.
AB  - Brugada syndrome, an autosomal dominantly inherited form of ventricular
      fibrillation characterized by ST-segment elevation in leads V1-V3 and right
      bundle-branch block on surface electrocardiogram, is caused by mutations in the
      cardiac sodium channel gene SCN5A. Patients with Brugada syndrome were studied
      using single-strand conformation polymorphism analysis, denaturing high
      performance liquid chromatography, and DNA sequencing of SCN5A. Mutations were
      identified in SCN5A in two families and one sporadic case. In one family, a
      missense mutation leading to a glycine to valine substitution (G351V) in the pore
      region between the DIS5 and DIS6 transmembrane segments was detected. Biophysical
      analysis demonstrated that this mutation caused significant current reduction. In
      the other family, a 20-bp deletion of the exon 5 splice acceptor site was
      identified; as exon 5 encodes part of the intracellular loop between DIS2 and
      DIS3, this portion of the channel is disrupted. In the sporadic patient, a
      missense mutation resulting in the substitution of lysine by glutamic acid
      (K126E) in the intracellular loop at the boundary with DIS1 was identified. These
      three new SCN5A mutations in Brugada syndrome patients are all located within
      domain I of SCN5A, a region not previously considered important in the
      development of ventricular arrhythmias.

PMID- 12051965
TI  - S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking
      cystathionine beta-synthase.
AB  - Elevated plasma homocysteine is associated with a variety of diseases in humans
      including coronary heart disease, stroke, peripheral vascular disease, and birth
      defects. However, the mechanism by which plasma homocysteine affects cells is
      unknown. We have examined the growth of isogenic wild-type and cystathionine beta
      synthase (CBS) deficient yeast in response to homocysteine and its immediate
      metabolic precursor, S-adenosylhomocysteine (SAH). CBS deficient yeast export
      significantly more homocysteine into the media than wild-type yeast and have
      elevated internal pools of homocysteine and SAH. We found that 5 mM homocysteine
      added to the media had very little effect on the growth of wild-type or CBS
      deficient yeast, although intracellular homocysteine concentrations increased
      five- to tenfold. In contrast, as little as 25 microM S-adenosylhomocysteine
      inhibited the growth of CBS deficient yeast, but had no effect on wild-type
      yeast. Measurements of the intracellular S-adenosylmethionine (SAM) and SAH
      indicate that CBS deficient yeast contain reduced SAM/SAH ratios relative to wild
      type, and this ratio is further reduced by adding SAH to the media. Growth
      inhibition by SAH in CBS deficient yeast can be totally reversed by addition of
      SAM to the media, indicating that the ratio and not absolute level is critical
      for cell growth. These results suggest that CBS plays a key role in the
      regulation of the SAM/SAH ratio inside cells and that excessive perturbations of
      this ratio can inhibit growth. We hypothesize that elevated extracellular
      homocysteine present in humans may reflect an altered intracellular SAM/SAH ratio
      and that this may be related to disease pathogenesis.

PMID- 12051966
TI  - Loss of cell anchorage triggers apoptosis (anoikis) in primary mouse hepatocytes.
AB  - Liver cell isolation and transplantation have been successfully performed in
      animal models and in humans. However, lack of initial engraftment due to cell
      death is a major roadblock to achieving clinical significance. Apoptosis was
      recently identified as an important cause of freshly isolated and banked
      hepatocyte cell death [Cell Transplant. 10 (2001) 59]. Pathways involving
      detachment-induced apoptosis (anoikis) are well characterized in other cell
      types. Loss of cell anchorage occurs during the hepatocyte isolation procedure
      prior to cell transplantation, but little is known about the role of this pathway
      in the survival of isolated hepatocytes. We report early occurrence of anoikis in
      primary mouse hepatocytes cultured under detached conditions on glass plates as
      compared to under attached conditions on plastic plates. Apoptosis in detached
      cells was determined using complementary techniques (DNA laddering, cell death
      ELISA assay, TUNEL assay and morphological analysis) and was detected as early as
      15 min after culture under detached conditions. Further analysis of the
      mechanisms inducing apoptosis during liver cell isolation and transplantation and
      of ways to prevent them could lead to improved clinical protocols of liver cell
      therapies.

PMID- 12051967
TI  - Alkaptonuria in Slovakia: thirty-two years of research on phenotype and genotype.
AB  - Research on alkaptonuria (AKU; OMIM # 230500) in Slovakia started in 1968 by the
      Research Laboratory (later on the Institute) for Clinical Genetics at Martin. Its
      first stage was focused on clinical, biochemical, genetic and epidemiologic
      questions and on the reasons for the high prevalence of AKU in Slovakia. Based on
      a screening programme of now over 611,000 inhabitants (509,000 newborns) the
      world-wide highest incidence of AKU (1 in 19,000) was recorded, and a total of
      208 patients (110 children) were registered. Extensive genealogical studies
      (sometimes over two centuries) resulted in the fusion of several "unrelated"
      nuclear families into larger pedigrees and enabled tracing most AKU ancestors to
      their original geographic localities, predominantly in remote mountain areas. A
      likely founder effect was detected among the shepherd population of the so-called
      Valachian colonization that resulted in a high degree of inbreeding and
      persisting genetic isolation. These epidemiologic data formed the basis for
      molecular studies in collaboration with the Wurzburg group. The AKU locus was
      mapped to human chromosome 3q2 by orthology to the mouse locus aku. Following the
      cloning of the homogentisate-1,2 dioxygenase (HGD) genes from human and mouse,
      nine different mutations were identified in 21 AKU index patients. These include
      4 missense, 2 splice-site, 2 single-base insertion and 1 deletion mutation. The
      most frequent mutations among the 42 AKU chromosomes of the index cases are
      c.648G > A (Gly161Arg; 42.9%), and c.1278insC (Pro370fs; 19.1%). To date, the
      genotypes of 29 patients and of 74 gene carriers from 21 families have been
      established. The highest prevalence and allelic heterogeneity were observed in
      the Kysuce district with five different mutations. Molecular epidemiology studies
      by haplotyping were carried out to uncover the original geographic localities of
      all AKU index chromosomes. This strongly suggests that several founders have
      contributed to the HGD gene mutation pool. While there is no straightforward
      explanation for the clustering of independent mutations, the genetic isolation in
      the past is likely to be responsible for the high prevalence of AKU in Slovakia.

PMID- 12051968
TI  - Macrophage inducible nitric oxide synthase gene expression is blocked by a
      benzothiophene derivative with anti-HIV properties.
AB  - Nitric oxide (NO) has been shown to mediate multiple physiological and
      toxicological functions. The inducible nitric oxide synthase (iNOS) is
      responsible for the high output generation of NO by macrophages following their
      stimulation by cytokines or bacterial antigens. The inhibition of TNF alpha
      stimulated HIV expression and the anti-inflammatory property of PD144795, a new
      benzothiophene derivative, have been recently described. We have now analyzed
      whether some of these properties could be mediated by an effect of PD144795 on NO
      dependent inflammatory events. We show that PD144795 suppresses the
      lipopolysaccharide-elicited production of nitrite (NO(-)(2)) by primary
      peritoneal mouse macrophages and by a macrophage-derived cell line, RAW 264.7.
      This effect was dependent on the dose and timing of addition of PD144795 to the
      cells. Suppression of NO(-)(2) production was associated with a decrease in the
      amount of iNOS protein, iNOS enzyme activity and mRNA expression. The effect of
      PD144795 was partially abolished by coincubation of the cells with LPS and IFN
      gamma. However, the inhibitory effect of PD144795 was not abrogated by the
      simultaneous addition of LPS and TNF alpha, which indirectly suggests that the
      effect of PD144795 was not due to the inhibition of TNF alpha synthesis.
      Additionally, PD144795 did not block NF-kappa B nuclear translocation induced by
      LPS. Inhibition of iNOS gene expression represents a novel mechanism of PD144795
      action that underlines the anti-inflammatory effects of this immunosuppressive
      drug.

PMID- 12051969
TI  - UCP5/BMCP1 transcript isoforms in human skeletal muscle: relationship of the
      short-insert isoform with lipid oxidation and resting metabolic rates.
AB  - Uncoupling protein 5 (UCP5) or brain mitochondrial carrier protein-1 (BMCP1)
      enhances mitochondrial proton leak in vitro and its hepatic and brain expression
      profiles are modulated by diet and cold exposure in mice. Alternative splicing
      generates three isoforms: a long form (UCP5L), a short form (UCP5S), and a short
      form with a 31 amino acid insert (UCP5SI). We investigated the relationship
      between skeletal muscle UCP5 expression and in vivo energy metabolism in 36 non
      diabetic Pima Indians. We determined the expression levels of total UCP5 (UCP5T),
      and the isoforms UCP5L, UCP5S, and UCP5SI (66.8, 32.5, and 0.8% of UCP5T,
      respectively). None correlated with body weight or percent body fat. The
      transcript level of UCP5SI, but not the others, was positively correlated with
      resting metabolic rate (r=0.38, P=0.02, adjusted for age, sex, fat mass, and fat
      free mass) and lipid oxidation rate (adjusted for age, sex, and percent body fat)
      during a euglycemic clamp with infusion of insulin at a physiologic concentration
      (r=0.42, P=0.01).

PMID- 12051970
TI  - Two issues in archaeological phylogenetics: taxon construction and outgroup
      selection.
AB  - Cladistics is widely used in biology and paleobiology to construct phylogenetic
      hypotheses, but rarely has it been applied outside those disciplines. There is,
      however, no reason to suppose that cladistics is not applicable to anything that
      evolves by cladogenesis and produces a nested hierarchy of taxa. This includes
      cultural phenomena such as languages and tools recovered from archaeological
      contexts. Two methodological issues assume primacy in attempts to extend
      cladistics to archaeological materials: the construction of analytical taxa and
      the selection of appropriate outgroups. In biology the species is the primary
      taxonomic unit used, irrespective of the debates that have arisen in phylogenetic
      theory over the nature of species. Also in biology the phylogenetic history of a
      group of taxa usually is well enough known that an appropriate taxon can be
      selected as an outgroup. No analytical unit parallel to the species exists in
      archaeology, and thus taxa have to be constructed specifically for phylogenetic
      analysis. One method of constructing taxa is paradigmatic classification, which
      defines classes (taxa) on the basis of co-occurring, unweighted character states.
      Once classes have been created, a form of occurrence seriation-an archaeological
      method based on the theory of cultural transmission and heritability-offers an
      objective basis for selecting an outgroup.

PMID- 12051971
TI  - Analysis of protein homeostatic regulatory mechanisms in perturbed environments
      at steady state.
AB  - Nine different protein homeostatic regulatory mechanisms were analysed for their
      ability to maintain a generic protein P within a specified range of a set-point
      steady-state concentration while perturbed by external processes that altered the
      rates at which P was produced and/or consumed. Steady state regulatory
      effectiveness was defined by the area within a rectangular region of
      "perturbation space", where axes correspond to rates of positive and negative
      perturbations. The size of this region differed in accordance with the regulatory
      elements composing the homeostatic mechanism. Such elements included basic
      negative feedback control of transcription (in which P, at some high
      concentration relative to its set-point value, binds to the gene G that encodes
      it, thereby inhibiting transcription), multiple sequential binding of a feedback
      effector (two P's bind sequentially to G), and dimerization of a feedback
      effector (a P(2) dimer binds to G). Two homeostatic mechanisms included a cascade
      structure, one with and one without translational feedback control. Another
      mechanism included feedback control of P degradation. Finally, two mechanisms
      illustrated the limits of regulatory systems. One lacked all regulatory elements
      (and included only an invariant rate of P synthesis and degradation) while the
      other assumed perfect (Boolean) regulation, in which transcription is completely
      inhibited at [P]>[P](sp) and is fully active at [P]<[P](sp). All of the systems
      evaluated are known, but the analytical expressions developed here allow
      quantitative comparisons between them. These expressions were evaluated at values
      typical of the average protein in Escherichia coli. A method for building
      regulatory networks by linking semi-independent regulatory modules is discussed.

PMID- 12051972
TI  - Sign-reversal during persistent activation in mu-opioid signal transduction.
AB  - A concept of signal transduction in biological systems specifies that any
      instantaneous input is appreciated by its departure from the moving average of
      past activity. The concept provides an adequate account of the occurrence of both
      the one-directional (e.g. analgesic) effects induced by opioid receptor
      activation, and of the contra-directional (e.g. hyperalgesic) effects that can be
      observed when activation is discontinued. Following this transduction concept,
      the numerical simulations reported here revealed, remarkably, that under some
      parametric conditions, the input's effect may reverse even as input is maintained
      at a constant magnitude. In in vitro conditions that are proximal to the signal
      transduction that occurs when an opioid agonist binds to the G-protein coupled
      opioid receptor, the effects of opioid receptor activation were monitored by
      measuring time-dependent Ca(2+) responses in CHO-K1 cells transfected with a mu
      opioid receptor and G(alpha 15) protein. The results indicate morphine to produce
      an initial increase in intracellular Ca(2+) concentration followed by a decrease
      below basal level. The occurrence of a sign-reversal was confirmed in native
      conditions of receptor-to-G protein coupling; the continuous in vivo infusion
      over a 2-week period of 0.31 mg rat(-1)day(-1) of fentanyl initially caused an
      increase of the mechanical threshold to induce a pain response (i.e. analgesia)
      that was followed by a decrease (i.e. hyperalgesia). The findings indicate that
      with opioid signaling systems, transduction mechanisms operate that may cause the
      sign of the effect to reverse not only when activation is discontinued but also
      whilst it is maintained at a constant magnitude.

PMID- 12051973
TI  - Energy storage and the evolution of population dynamics.
AB  - We explore the mutual dependence of life history evolution and population
      dynamics by modeling a structured rotifer population that preys on a dynamic food
      supply. We focus on the ecological role of energy storage. A physiologically
      based submodel describes how individual predators allocate assimilated energy
      among growth, reproduction, and storage. We use invasibility analyses to predict
      evolutionary stable strategies for energy allocation. Various proxy measures of
      fitness based on measurable biological quantities, such as average population
      size or average per-capita fecundity, fail to predict evolutionary stable
      strategies. The predicted strategies indicate that selection strongly favors
      storage allocation for juveniles, but only for adults when prey densities are
      high. With the evolution of energy storage, population dynamics can shift from
      aperiodic to stable cycles without any need to invoke group selection.

PMID- 12051975
TI  - An inverting basket model for AE1 transport.
AB  - We describe an "inverting basket" model for transport in the erythrocyte anion
      exchanger, AE1. The inverting basket is formed by the side chains of three
      putative key residues, two positively (Lys 826 and Arg 730) and one negatively
      (Glu 681) charged residue. We have tentatively chosen seven transmembrane
      helices, TM1, TM2, TM4, TM8, TM10, TM12 and TM13 to form a conical channel using
      the well-established Glu 681 of TM8 and candidates Lys 826 and Arg 730 of TM12-13
      and TM10, respectively, to form the inverting basket. We assume that these
      residues bind to an anion and shift from outward facing (C(o)) to inward facing
      (C(i)) conformation without significant backbone movements to transport an anion
      across the membrane. The transition of the complex (residues and ion) from
      outward facing (C(o)) to inward facing (C(i)) constitutes one "basket" inversion.
      The barrier to inversion is composed of two major components: that of the
      anhydrous complex, which we refer to as a steric energy barrier and a dehydration
      effect due to the removal of charges in the complex from water in the channel.
      The steric barrier is dependent on the side chain charge and configuration and on
      the ion charge and size. The dehydration effect, for our model, ameliorates the
      steric barrier, in the case of the empty complex but less so for the monovalent
      and divalent ions. We conclude, that it is possible for a seven-helix bundle to
      have a steric barrier to basket inversion, but that hydration effects in thin
      hydrophobic barrier models may be more complex than usually envisioned.

PMID- 12051974
TI  - Modelling complex populations formed by proliferating, quiescent and quasi
      quiescent cells: application to plant root meristems.
AB  - A proliferating population of cells may be considered complex when its
      proliferative or growth fraction P is lower than 1 and/or when it is formed by
      subpopulations with different mean cycle times. The present paper shows that in
      such complex populations exponential growth is consistent with a steady-state
      distribution of cells. Obviously, when P=1 then cell distribution is only a
      function of cell age. An analytical model has been developed to study complex
      populations including both quiescent fractions formed by cells with unreplicated
      genome (G(0) cells) and cells with fully duplicated chromosomes (Q(2) cells). The
      model also considers those quasi-quiescent cells in their last transit through
      G(1) and S (Q(1) and Q(s) cells) before becoming quiescent. In order to solve the
      difficulties of a direct analysis of the whole population, its kinetic parameters
      have been obtained by studying the negative exponential distribution of two
      subpopulations: one formed by the proliferating cells and another formed by the
      quasi-quiescent cells. Additionally, the model could be applied when quiescence
      is initiated at any other cycle phase different from G(1) and G(2), for instance,
      cells in the process of replicating their DNA or being at any other mitotic
      phases. The utility of the method was illustrated in populations which constitute
      the root meristems of both Allium cepa L. and Pisum sativum L. Three facts should
      be stressed: (1) the method seems to be rather powerful because it can be carried
      out from different sets of experimentally measured parameters; (2) the rate of
      division and, therefore, the population doubling time can be easily estimated by
      this method; and (3) it also allows the determination of the amount of cells that
      had become quiescent either before they had replicated their DNA (G(0)) or after
      having completed their replication (Q(2)), as well as those quasi-quiescent cells
      which are progressing throughout their last pre-replicative and replicative
      periods (thus Q(1) and Q(s), respectively).

PMID- 12051976
TI  - Markers of disease evolution: the case of tuberculosis.
AB  - Abrupt changes in environmental conditions--broadly understood to include
      demographic and social dynamics--can seriously impact the local or global disease
      dynamics of a population. These changes in the evolutionary landscape, which may
      occur over relatively short time-scales, are very likely to play a critical role
      in disease evolution. The potential impact of demographic, social and
      epidemiological shifts on the evolution of tuberculosis epidemics in the United
      States over the past century and a half is the main subject of this article.
      Evidence is provided to support the hypothesis that the observed substantial
      decreases in the incidence of active tuberculosis are the result of abrupt
      reductions in the rates of disease progression.

PMID- 12051977
TI  - Dependence of control coefficient distribution on the boundaries of a metabolic
      system: a generalized analysis of the effects of additional input and output
      reactions to a linear pathway.
AB  - Both experimental and theoretical studies of metabolism are likely to relate to a
      segment that has been isolated for analytical purposes. In practice, it will be
      embedded in the whole of cellular metabolism. Thus, it is necessary to consider
      how conclusions about the control of an isolated pathway may be modified in this
      wider context where the input and output metabolites are considered as variables
      of cellular metabolism. Here, we analyse the effect of expanding a linear
      metabolic pathway by adding an extra input or an extra output. In particular, we
      analyse the effect of the elasticities of the extra steps on control
      coefficients. We derive matrix algebraic relationships for obtaining flux and
      concentration control coefficients from expressions depending on these extra
      elasticities and on parameters (elasticities and control coefficients) of the
      original pathway. These equations can be shown in certain cases to be generalized
      versions of earlier rescaling relationships and to be related to top-down
      analysis, but also apply where the new variable metabolite of the expanded
      pathway is an effector of more than one step of the original pathway. We use our
      relationships to analyse the dependence or independence of control coefficients
      upon these extra elasticities for the published analyses of the pathway of
      mammalian serine biosynthesis (Fell & Snell, 1988) and Escherischia coli
      threonine biosynthesis (Chassagnole et al., 2001). The same analysis can be
      applied to determine whether the transport reactions of substrates and products
      of a pathway in and out of a cell need to be included in estimations of the
      control coefficients of the enzymes.

PMID- 12051978
TI  - A population dynamic model for facultative agamosperms.
AB  - Plants that can reproduce both sexually and agamically are called facultative
      apomicts. Some species, such as Taraxacum, contain both sexual diploids and
      triploid facultative apomicts. Triploids produce seeds without gamete fusion and
      recombination, and can also produce pollen and fertilize diploids. We present a
      population dynamic model that deals with gene flow and competition between
      diploids and triploids, with differing allocation towards reproductive investment
      in seeds and pollen. This paper examines whether diploids and triploids of plants
      with facultative agamospermy can coexist within a single population. We analyse
      the global behavior of such a dynamic system. Features of the system are
      significantly affected by the germination rates of diploids and triploids. Either
      diploids or triploids persist alone when the germination rate of diploids is
      sufficiently larger or smaller than that of triploids, respectively. Competitive
      exclusion occurs when both germination rates are sufficiently large. Coexistence
      is possible under certain specific conditions when: (I) the germination rates of
      both diploid sexuals and triploids are not sufficiently large, and (II) triploids
      produce sufficient pollen. When diploid sexuals and triploids coexist, triploids
      cannot exist alone, implying that the pollen of triploids is necessary to exploit
      diploid ovules.

PMID- 12051979
TI  - Design issues for the Michaelis-Menten model.
AB  - We discuss design issues for the Michaelis-Menten model and use geometrical
      arguments to find optimal designs for estimating a subset of the model
      parameters, or a linear combination of the parameters. We propose multiple
      objective optimal designs when the parameters have different levels of interest
      to the researcher. In addition, we compare six commonly used sequence designs in
      the biological sciences for estimating parameters and, propose optimal choices
      for the parameters for geometric designs using closed-form efficiency formulas.

PMID- 12051980
TI  - Ab initio GB study of methylation reaction of adenine, cytosine, guanine, and
      thymine by methanediazonium ion.
AB  - Methylation reaction at ten nucleophilic sites in four DNA base molecules by
      methanediazonium ion (N(2)Me+) was examined by ab initio MO/GB calculation which
      includes the solvent effect with the continuum model using the generalized Born
      formula. The stabilization energy of the ion-dipole complex as well as the energy
      of the transition state are roughly consistent with the experimental fraction of
      methylation by N -methyl- N -nitrosourea. For the guanine N7 site, which is the
      principal site of methylation, the stabilization energy is the largest and the
      energy of the transition state is low. The reactions at the guanine O6 and N7
      sites were analysed by drawing the potential energy surface with respect to two
      parameters, the O6-C(Me) distance and the N7-C(Me) distance. The methylation
      reactions of the guanine O6 and N7 sites begin from the common geometry, the
      global minimum in the two-dimensional potential energy surface.

PMID- 12051981
TI  - Relationships between embolism, stem water tension, and diameter changes.
AB  - A model for embolism in the sapflow process was developed, in which embolism is
      described as a physical process linked to real physical properties of the
      conduits and the thermodynamic state of water. Different mechanisms leading to
      embolism and their effect on water relations and especially diurnal diameter
      changes in a tree were examined. The mechanisms of heterogeneous nucleation, air
      seeding, and bubble growth have been considered. The significance of embolism has
      been revealed here by examining diameter changes, which is an easily measurable
      quantity under field conditions. The most fundamental effects of embolism on
      sapflow are decrease in permeability and release of water from embolizing
      conduits to the transpiration stream. These can be indirectly detected by
      observing diameter changes. If possible changes in elasticity are not accounted
      for, embolism generally tends to enhance the amplitude of the diurnal diameter
      changes due to reduced permeability and increased tensions. In the case of
      reduced elasticity, embolism gives rise to smaller amplitudes of diameter
      changes.

PMID- 12051982
TI  - Population dynamic consequences of allee effects.
AB  - We take a well-known dynamic model of an isolated, unstructured population and
      modify this to include a factor that allows for a reduction in fitness due to
      declining population sizes, often termed an Allee effect. Analysis of the
      behaviour of this model is carried out on two fronts - determining the
      equilibrium values and examining the stability of these equilibria. Our results
      point to the stabilising effect on population dynamics of the Allee effect and an
      unexpected increase in stability with increased competition due to the
      interaction between competitive and Allee effects.

PMID- 12051983
TI  - The stability of cooperation involving variable investment.
AB  - In this paper, we attempt to reconcile the results of several studies which have
      investigated the evolution of cooperation between non-relatives in systems where
      investment in partners can vary. In contrast to previous proposals, we show for
      the first time that variable-investment cooperation can be readily maintained in
      inter-species mutualistic relationships even in the absence of spatial structure,
      but that the stability of this interaction is dependent on the particular
      investment-response rule that is employed. By allowing the evolution of
      investment-response parameters in both inter- and intra-specific versions of the
      continuous variable-investment Prisoners' Dilemma we show that, in the absence of
      further factors, the raise-the stakes (RTS) strategy is likely to evolve into a
      simpler, variable investment form of Give-as-Good-as-you-Get that initially
      offers a high fixed amount and subsequently matches its partner's investment.
      Nevertheless, we demonstrate that genuine RTS-like strategies will still be
      selected if two intuitively reasonable conditions hold: if individuals are
      limited in terms of the total they can invest in cooperative actions over their
      lifetimes, and if there are always some individuals in a population that cannot
      cooperate.

PMID- 12051984
TI  - Heterochronic detection through a function for the ontogenetic variation of bone
      shape.
AB  - Heterochrony, evolutionary modifications in the rates and/or the timing of
      development, is widely recognized as an important agent of evolutionary change.
      In this paper, we are concerned with the detection of this evolutionary mechanism
      through the analysis of long bone growth. For this, we provide a function sigma
      (t) for the ontogenetic variation of bone shape by taking the ratio of two
      Gompertz curves explaining, respectively, the relative contribution to long bone
      growth of (a) endochondral ossification and (b) periosteal ossification. The
      significance of the fitting of this function to empirical data was tested in Anas
      platyrhynchos (Anseriformes). In this function sigma (t), the time t(m) at which
      periosteal growth rate first equalizes endochondral growth rate was taken as the
      timing parameter to be compared between taxa. On the other hand, the maximum rate
      of ontogenetic change in bone shape (maximum slope, beta) from hatching to t(m)
      was taken as the rate parameter to be compared. Comparisons of these parameters
      between the plesiomorphic condition and the derived character state would provide
      evidence for hypomorphosis (earlier occurrence of t(m)), hyper-morphosis (delayed
      occurrence of t(m)), deceleration (smaller beta) or acceleration (higher beta).
      Regarding the phylogenetic context, the ancestral condition for the character of
      interest should be estimated to polarize the direction of the heterochronic
      change. We have quantified the influence of the phylogenetic history on the
      variation of adult bone shape in a sample of 13 species of Anseriformes and 17
      species from other neornithine orders of birds by using permutational
      phylogenetic regressions. Phylogenetic effects are significant, and this fact
      allows the optimization of bone shape onto a phylogenetic tree of Anseriformes to
      estimate the ancestral condition for Anas platyrhynchos.

PMID- 12051985
TI  - The genome-scale metabolic extreme pathway structure in Haemophilus influenzae
      shows significant network redundancy.
AB  - Genome-scale metabolic networks can be characterized by a set of systemically
      independent and unique extreme pathways. These extreme pathways span a convex,
      high-dimensional space that circumscribes all potential steady-state flux
      distributions achievable by the defined metabolic network. Genome-scale extreme
      pathways associated with the production of non-essential amino acids in
      Haemophilus influenzae were computed. They offer valuable insight into the
      functioning of its metabolic network. Three key results were obtained. First,
      there were multiple internal flux maps corresponding to externally
      indistinguishable states. It was shown that there was an average of 37 internal
      states per unique exchange flux vector in H. influenzae when the network was used
      to produce a single amino acid while allowing carbon dioxide and acetate as
      carbon sinks. With the inclusion of succinate as an additional output, this ratio
      increased to 52, a 40% increase. Second, an analysis of the carbon fates
      illustrated that the extreme pathways were non-uniformly distributed across the
      carbon fate spectrum. In the detailed case study, 45% of the distinct carbon fate
      values associated with lysine production represented 85% of the extreme pathways.
      Third, this distribution fell between distinct systemic constraints. For lysine
      production, the carbon fate values that represented 85% of the pathways described
      above corresponded to only 2 distinct ratios of 1:1 and 4:1 between carbon
      dioxide and acetate. The present study analysed single outputs from one organism,
      and provides a start to genome-scale extreme pathways studies. These emergent
      system-level characterizations show the significance of metabolic extreme pathway
      analysis at the genome-scale.

PMID- 12051986
TI  - A markov chain approach to calculate r(0) in stochastic epidemic models.
AB  - R(0) has been defined as "The expected number of secondary infections originated
      by a "typical" infective individual when introduced into a population of
      susceptibles", and it is perhaps the single most important parameter in epidemic
      models. A general framework to calculate R(0) that can be applied to complicated
      stochastic epidemic models that may include demography, several strains, latent
      or carrier-like states, with or without density-dependent parameters is
      introduced. This framework helps us to understand the concept of a "typical"
      infective individual used in the deterministic definition of R(0). The method is
      illustrated with applications to several epidemic models, including some in which
      it has been found that the disease may persist even if R(0)<1. It is shown that
      although the probability of extinction is difficult to calculate in these latter
      cases, it is possible to give general conditions on the parameters under which
      eventual extinction is certain.

PMID- 12051987
TI  - Metapopulation models for extinction threshold in spatially correlated
      landscapes.
AB  - Simple analytical models assuming homogeneous space have been used to examine the
      effects of habitat loss and fragmentation on metapopulation size. The models
      predict an extinction threshold, a critical amount of suitable habitat below
      which the metapopulation goes deterministically extinct. The consequences of non
      random loss of habitat for species with localized dispersal have been studied
      mainly numerically. In this paper, we present two analytical approaches to the
      study of habitat loss and its metapopulation dynamic consequences incorporating
      spatial correlation in both metapopulation dynamics as well as in the pattern of
      habitat destruction. One approach is based on a measure called metapopulation
      capacity, given by the dominant eigenvalue of a "landscape" matrix, which
      encapsulates the effects of landscape structure on population extinctions and
      colonizations. The other approach is based on pair approximation. These models
      allow us to examine analytically the effects of spatial structure in habitat loss
      on the equilibrium metapopulation size and the threshold condition for
      persistence. In contrast to the pair approximation based approaches, the
      metapopulation capacity based approach allows us to consider species with long as
      well as short dispersal range and landscapes with spatial correlation at
      different scales. The two methods make dissimilar assumptions, but the broad
      conclusions concerning the consequences of spatial correlation in the landscape
      structure are the same. Our results show that increasing correlation in the
      spatial arrangement of the remaining habitat increases patch occupancy, that this
      increase is more evident for species with short-range than long-range dispersal,
      and that to be most beneficial for metapopulation size, the range of spatial
      correlation in landscape structure should be at least a few times greater than
      the dispersal range of the species.

PMID- 12051988
TI  - Functional modules of the brain.
AB  - Building on the view of massive modularity, a number of generalized assumptions
      lead to an entirely new concept of functional brain modules. In contrast to the
      nerve centers usually considered to be active in the brain, these modules, called
      symbions, are non-localized, non-hierarchical, and based on subcellular molecular
      mechanisms rather than on neurons. They act according to local rules that may be
      fundamentally nonlinear, potentially leading to strong interdependencies between
      parallel inputs, and they interact by information, not by force. The existence of
      inner states, feedback loops, internal models, and information encoding provide
      the basis for a higher complexity than is usually assumed in neuroscience. A map
      of the symbion world, showing functional rather than physical localization, can
      be used to illustrate symbion interaction patterns. Perceptual constancy, sensory
      illusions, visual cognition, and eye-hand coordination are used as examples of
      what can be explained by using the new theory.

PMID- 12051989
TI  - Spatially explicit models of Turelli-Hoffmann Wolbachia invasive wave fronts.
AB  - This paper examines different mathematical models of insect dispersal and
      infection spread and compares these with field data. Reaction-diffusion and
      integro-difference equation models are used to model the spatio-temporal spread
      of Wolbachia in Drosophila simulans populations. The models include cytoplasmic
      incompatibility between infected females and uninfected males that creates a
      threshold density, similar to an Allee effect, preventing increase from low
      incidence of infection in the host population. The model builds on an earlier
      model (Turelli & Hoffmann, 1991) by incorporating imperfect maternal
      transmission. The results of simulations of the models using the same parameter
      values produce different dynamics for each model. These differences become very
      marked in the integro-difference equation models when insect dispersal patterns
      are assumed to be non-Gaussian. The success or failure of invasion by Wolbachia
      in the simulations may be attributed to the insect dispersal mechanism used in
      the model rather than the parameter values. As the models predict very different
      outcomes for the integro-difference models depending on the underlying
      assumptions of insect dispersal patterns, this emphasizes that good field data on
      real (rather than idealized) dispersal patterns need to be collected before
      models such as these can be used for predictive purposes.

PMID- 12051990
TI  - Polychlorinated biphenyl-induced apoptosis of murine spleen cells is aryl
      hydrocarbon receptor independent but caspases dependent.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants and
      many of their toxic effects, including their immunotoxicities, are mediated by
      the activation of aryl hydrocarbon receptor (AhR). We previously reported that
      Aroclor 1254, one of the most widely used PCB mixtures, increased DNA
      fragmentation in mouse spleen cells, suggesting that apoptosis was correlated
      with the immunotoxicity of PCB (Yoo et al., Toxicol. Lett. 91, 83-89, 1997). In
      the present study we investigated the mechanism by which PCB induces apoptosis
      and the involvement of AhR in the PCB-mediated apoptosis of mouse spleen cells.
      Aroclor 1254 induced DNA fragmentation without AhR activation, and the apoptosis
      was unaffected by alpha-naphtoflavone, a well-known antagonist of AhR. Moreover,
      the PCB congeners (PCB 47, 52, 128, and 153), which have little affinity for AhR,
      induced DNA fragmentation, whereas congeners (PCB 77, 126, and 169) that have
      high affinity for AhR did not induce fragmentation. The di-ortho form of PCB (PCB
      153) and Aroclor 1254 induced DNA fragmentation in the spleen cells of both AhR
      knockout mice and Ah low-response mice, whereas the non-ortho form of PCB (PCB
      126) did not induce DNA fragmentation. In the light of these findings, it is
      evident that AhR is not involved in PCB-mediated apoptosis. PCB 153 significantly
      increased caspase-3 activity in both spleen cells and human leukemia cells, and z
      VAD-fmk, a general inhibitor of caspases, prevented PCB-induced DNA
      fragmentation. Based on our findings, the most likely mechanism that can account
      for this biological effect involves the induction of caspase-dependent apoptotic
      cell death.

PMID- 12051991
TI  - Aroclor 1254 modulates gene expression of nuclear transcription factors:
      implications for albumin gene transcription and protein synthesis in rat
      hepatocyte cultures.
AB  - Human exposure to polychlorinated biphenyls (PCBs) may lead to increased albumin
      serum levels, but little is known about the underlying events. Certain PCBs are
      also ligands for the aryl hydrocarbon receptor (Ahr) and this receptor regulates
      transcriptional activation of many different genes, including CYP1A1. We tested
      our hypothesis that expression of certain nuclear transcription factors is
      altered upon treatment of rat hepatocyte cultures with Aroclor 1254 and we
      studied the gene expression of albumin and liver-enriched transcription factors
      simultaneously. We correlate albumin gene expression with protein synthesis and
      we used CYP1A1 gene expression and enzyme activity as a surrogate endpoint for
      aryl hydrocarbon receptor activation. We found mRNA transcripts of CCAAT/enhancer
      binding protein alpha and gamma, hepatic nuclear factor 1, and hepatic nuclear
      factor 4 to be increased up to 62-fold, whereas albumin gene expression and
      secretion was increased 3-fold. Noticeably, expression of c-fos, c-jun (AP-1),
      HNF-6, CCAAT/enhancer binding protein beta and delta, tissue-specific enhancer-1,
      Ah-receptor, and albumin D-site-binding protein was unchanged. We show coordinate
      albumin gene expression and protein secretion in primary rat hepatocyte cultures
      and propose a relationship between induction of certain liver-enriched
      transcription factors and of the albumin gene via an Ahr-mediated mechanism.

PMID- 12051992
TI  - Selective effects of cyclodiene insecticides on dopamine release in mammalian
      synaptosomes.
AB  - Cyclodiene insecticides release labeled neurotransmitter in striatal and cortical
      synaptosome preparations under nondepolarizing conditions, typically showing half
      maximal potencies for release in the low micromolar range. This level of potency
      is similar to those reported for inhibition of 36Cl- influx at the gamma
      aminobutyric acid (GABA)(A) receptor, their consensus target site. A wide variety
      of other GABA(A) antagonists, including picrotoxinin and bicuculline, did not
      cause significant dopamine release, which obviated direct involvement of the
      GABA(A) receptor as a possible site of action. Release assays with different
      transmitters indicated that striatal dopaminergic terminals are severalfold more
      sensitive to release than other neurotransmitter types. The selective sensitivity
      of nigrostriatal dopaminergic nerve terminals to insecticidal organochlorines
      provides biochemical evidence supporting an epidemiological linkage between
      exposure to environmental toxicants and Parkinsonism.

PMID- 12051993
TI  - Early inflammatory response to asbestos exposure in rat and hamster lungs: role
      of inducible nitric oxide synthase.
AB  - Recent studies have suggested that inducible nitric oxide synthase (iNOS) plays a
      role in the development of asbestos-related pulmonary disorders. The pulmonary
      reactions of rats and hamsters upon exposure to asbestos fibers are well known to
      be disparate. In addition, in vitro experiments have indicated that mononuclear
      phagocytes from hamsters, in contrast to those from rats, lack the iNOS pathway.
      Therefore, the purpose of this study was to investigate whether rats and hamsters
      differ in lung iNOS expression in vivo upon exposure to asbestos fibers and
      whether differences in iNOS induction are associated with differences in the
      acute pulmonary inflammatory reaction. Body weight, alveolar-arterial oxygen
      difference, differential cell count in bronchoalveolar lavage fluid, total
      protein leakage, lung myeloperoxidase activity and lipidperoxidation, wet/dry
      ratio, iNOS mRNA and protein expression, and nitrotyrosine staining of lung
      tissue were determined 1 and 7 days after intratracheal instillation of asbestos
      fibers in CD rats and Syrian golden hamsters. Exposure of rats to asbestos fibers
      resulted in enhanced pulmonary iNOS expression and nitrotyrosine staining
      together with an acute inflammation that was characterized by an influx of
      neutrophils, enhanced myeloperoxidase activity and lipid peroxidation, damage of
      the alveolar-capillary membrane, edema formation, and impairment of gas exchange.
      In comparison, instillation of asbestos fibers in hamsters resulted in a
      significantly milder inflammatory reaction of the lung with no induction of iNOS
      in pulmonary cells. The data obtained provide important information to understand
      the underlying mechanisms of species differences in the pulmonary response upon
      exposure to asbestos fibers.

PMID- 12051994
TI  - Differential induction of heme oxygenase-1 in macrophages and hepatocytes during
      acetaminophen-induced hepatotoxicity in the rat: effects of hemin and biliverdin.
AB  - Heme oxygenase-1 (HO-1), also known as heat shock protein 32, has been shown to
      protect against oxidant-induced tissue injury. In the present studies, we
      analyzed expression of this enzyme in macrophages and hepatocytes following
      acetaminophen administration and its potential role in hepatotoxicity. Treatment
      of rats with a hepatotoxic dose of acetaminophen (1 g/kg, ip) resulted in a time
      dependent induction of HO-1 in the liver. This was observed within 6 h of
      acetaminophen administration in both hepatocytes and macrophages. Hepatocytes
      were found to be more sensitive than macrophages to the effects of acetaminophen
      on HO-1. Up regulation of HO-1 in the liver following acetaminophen
      administration correlated with induction of ferritin and manganese superoxide
      dismutase (MnSOD). To determine if HO-1 was hepatoprotective, rats were
      pretreated with hemin (30 micromol/kg, ip), a potent inducer of the enzyme.
      Following hemin treatment, we observed a time-dependent increase in HO-1 protein
      in the liver and in serum bilirubin levels. Pretreatment of rats with hemin was
      found to prevent acetaminophen-induced hepatotoxicity, as measured histologically
      and biochemically by decreased serum transaminase levels. This was correlated
      with more rapid increases in expression of hepatic ferritin and MnSOD. Heme
      metabolism via HO-1 generates biliverdin, which is rapidly converted to bilirubin
      by biliverdin reductase. Pretreatment of rats with biliverdin (40 micromol/kg,
      ip) was also found to block acetaminophen-induced injury. These data suggest that
      HO-1 is an important component of antioxidant defense during acetaminophen
      induced hepatotoxicity.

PMID- 12051995
TI  - Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8
      tetrachlorodibenzo-p-dioxin in activated B cells.
AB  - B cells have been identified as sensitive cellular targets responsible for
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated suppression of humoral
      immunity. In previous studies, TCDD was shown to produce a significant inhibition
      of IgM secretion and mu gene expression in LPS-activated CH12.LX B cells (AhR
      expressing) but not in BCL-1 B cells (AhR deficient). The present studies extend
      these previous findings by investigating the effect of TCDD on AP-1 and nuclear
      factor (NF)-kappaB, both of which play an important role in B-cell activation,
      differentiation, and immunoglobulin (Ig) gene expression. Electrophoretic
      mobility shift assays and chloramphenicol acetyl transferase reporter gene
      experiments demonstrated that lipopolysaccharide (LPS)-induced DNA binding and
      transcriptional activity of AP-1 was markedly inhibited by TCDD at 24, 48, and 72
      h after cellular activation of CH12.LX cells. Conversely, TCDD treatment produced
      no significant change on the activity of NF-kappaB. Two AhR antagonists, alpha
      naphthoflavone and 2,2',5,5'-tetrachlorobiphenyl, attenuated TCDD-induced
      inhibition of AP-1 binding in CH12.LX cells. Concordant with this result, TCDD
      did not inhibit LPS-induced AP-1 activity in BCL-1 B cells. Moreover, supershift
      analysis revealed the major component of the AP-1 complex in LPS-activated
      CH12.LX cells was c-Jun. Additional studies revealed that the nuclear c-jun and c
      jun steady-state mRNA expression was inhibited by TCDD treatment. Collectively,
      these results suggest that TCDD-induced inhibition of IgM expression by B cells
      may be mediated, at least in part, through a down-regulation of AP-1 activity in
      an AhR-dependent manner.

PMID- 12051996
TI  - Impairment of the cell-to-matrix adhesion and cytotoxicity induced by Bothrops
      moojeni snake venom in cultured renal tubular epithelia.
AB  - Bothrops moojeni snake venom induces acute renal failure (ARF) as a consequence
      of morphological and functional alterations in glomerular and tubular cells. It
      is still unclear whether the ARF results from a direct cytotoxic effect on renal
      epithelia or from a renal ischemia due to systemic hemodynamic disturbances. This
      work investigated the in vitro effect of B. moojeni crude venom, using cultured
      Madin-Darby canine kidney (MDCK) monolayers as a model. The crude venom induced a
      significant time- and dose-dependent decrease in transepithelial electrical
      resistance across MDCK monolayers. In addition, the exposure to the venom
      resulted in cell detachment from the substratum, as revealed by transmission
      electron microscopy. Immunocytochemical analysis showed no change in the
      distribution of some junctional proteins, such as occludin, ZO-1, and E-cadherin.
      Nevertheless, the staining with labeled phalloidin revealed a disarray of the
      cytoskeleton, specifically of the stress fibers and of the focal adhesion
      associated F-actin at the cell-to-matrix contact region. The treatment with B.
      moojeni venom also increased the cell release of lactate dehydrogenase and
      decreased cellular uptake of the vital neutral red. In conclusion, B. moojeni
      crude venom appears to have a direct cytotoxic effect on a renal tubule-derived
      cell line, also inducing impairment of the cell-matrix interaction.

PMID- 12051997
TI  - Acetaminophen-induced inhibition of Fas receptor-mediated liver cell apoptosis:
      mitochondrial dysfunction versus glutathione depletion.
AB  - We reported previously that acetaminophen overdose interrupts the signaling
      pathway of Fas receptor-mediated apoptosis. The aim of our study was to
      investigate the mechanism of this effect. Male C3Heb/FeJ mice received a single
      dose of acetaminophen (300 mg/kg ip) and/or anti-Fas antibody Jo-2 (0.6 mg/kg
      iv). Some animals were treated with allopurinol (100 mg/kg po) 18 and 1 h before
      acetaminophen injection. After 90 min of Jo treatment, there was processing of
      procaspase-3 and a significant increase in liver caspase-3 activity, which is
      consistent with apoptotic cell death. Treatment with acetaminophen 2.5 h before
      Jo inhibited the increase in hepatic caspase-3 activity by preventing the
      processing of the proenzyme. When administered alone, acetaminophen did not
      induce caspase-3 activation but caused significant liver injury. Acetaminophen
      treatment alone caused mitochondrial cytochrome c release, depletion of the
      hepatic ATP content by 55%, and a 10-fold increase in mitochondrial glutathione
      disulfide levels. Pretreatment with allopurinol prevented the mitochondrial
      oxidant stress and liver injury due to acetaminophen toxicity but had no effect
      on Jo-mediated apoptosis. Allopurinol did not affect the initial glutathione
      depletion after acetaminophen. However, allopurinol restored the sensitivity of
      hepatocytes to Fas receptor signaling in acetaminophen-treated animals.
      Histochemical evaluation of DNA fragmentation with the TUNEL assay showed that
      acetaminophen eliminated Fas receptor-mediated apoptosis in all hepatocytes not
      just in the damaged cells of the centrilobular area. Our data suggest that
      acetaminophen-induced mitochondrial dysfunction and not the initial glutathione
      depletion is responsible for the interruption of Fas receptor-mediated apoptotic
      signaling in hepatocytes.

PMID- 12051998
TI  - Teratogen-induced activation of caspase-9 and the mitochondrial apoptotic pathway
      in early postimplantation mouse embryos.
AB  - Previously we showed that teratogen-induced cell death in mouse embryos is
      apoptotic in nature, i.e., involves the release of cytochrome c from mitochondria
      and the subsequent activation of caspase-3, cleavage of poly (ADP-ribose)
      polymerase (PARP), and internucleosomal DNA fragmentation. Herein we show that
      hyperthermia, 4-hydroperoxycyclophosphamide, and staurosporine also activate
      caspase-9, the apical caspase in the mitochondrial apoptotic pathway. Activation
      of procaspase-9 is associated with the cleavage of this proenzyme and the
      generation of two forms of the large subunit, primarily a 39-kDa subunit (p39)
      but also a lesser amount of a 37-kDa subunit (p37). We also present data that
      support the idea that the teratogen-induced formation of the p37 subunit in vivo
      occurs by the cytochrome c-mediated processing of procaspase-9, whereas the p39
      subunit is formed by an amplification loop involving caspase-3. We also
      previously showed that the release of cytochrome c, activation of caspase-3,
      cleavage of PARP, and DNA fragmentation are blocked in cells of the developing
      heart, which are resistant to teratogen-induced cell death. We now show that this
      block in the mitochondrial apoptotic pathway in heart cells extends to the
      activation of procaspase-9. Thus, our cumulative data indicate that hyperthermia,
      4-hydroperoxycyclophosphamide, and staurosporine induce cell death in Day 9 mouse
      embryos by activating the mitochondrial apoptotic pathway. In addition, our data
      suggest that cells of the Day 9 mouse embryo that are resistant to teratogen
      induced cell death possess multiple mechanisms for inhibiting the mitochondrial
      apoptotic pathway after a teratogenic exposure.

PMID- 12051999
TI  - A procedure for developing risk-based reference doses.
AB  - Reference doses (RfDs) for toxic substances based on a no observed adverse effect
      level (NOAEL) or lowest observed adverse effect level (LOAEL) are established to
      restrict human exposures to only nontoxic or minimally toxic levels. In order to
      calculate a risk-based RfD, for the point of departure it is necessary to replace
      a NOAEL or LOAEL by a benchmark dose (BMD) estimated to be associated with a
      specified level of estimable risk in or near the low end of an experimental dose
      range. Then the RfD is calculated by dividing the BMD by a series of uncertainty
      factors. Among these uncertainty factors is one for interindividual sensitivity,
      typically assigned a value of 10. If information is available on interindividual
      sensitivity, this default factor can be replaced with a factor expected to
      provide protection for a specified proportion of a population. Examination of
      published databases suggests interindividual effects often to be approximately
      log-normal. For example, in order to illustrate the procedure for establishing a
      risk-based RfD, a standard deviation of the logarithm (base e) of individual
      sensitivity of 1.7 was selected, i.e., a factor of 5.5. This value is near the
      upper range of values reported in the literature (D. Hattis et al., 1999, in
      "Characterizing Human Variability in the Risk Assessment Process," ILSI Press,
      Washington, DC). Using this information in combination with an RfD based on a
      benchmark dose associated with a specified level of risk, the risk at the RfD can
      be estimated. For example, a benchmark dose associated with a risk of 10% divided
      by 60, to account for interindividual variation, is expected to limit risk at the
      RfD to about 1 in 10,000. If the standard deviation of the logarithm (base e) of
      individual sensitivity is 1.2, a more typical value, the divisor is approximately
      20. These would replace an RfD having an unknown risk based on the LOAEL divided
      by 100. Or, an RfD with a specified level of risk could be estimated. The
      estimate of risk can be improved for a specific case by replacing an overall
      estimate of the standard deviation for interindividual variability by an estimate
      of the standard deviation for a particular class of chemicals and/or biological
      endpoint, if available. Risks can be substantially lower for smaller values of
      interindividual variability. Determination of an RfD still would require an
      additional uncertainty factor for animal to human extrapolation.

PMID- 12052000
TI  - An analysis of the mainstream smoke chemistry of samples of the U.S. cigarette
      market acquired between 1995 and 2000.
AB  - Surveys of the smoke composition of commercially marketed cigarettes were
      conducted in 1995, 1998, and 2000. For each of these surveys, the U.S. cigarette
      market was stratified into broad market sections based on "tar" category and
      menthol inclusion. Brand styles were selected from these market sections using
      techniques in which selection probability increased with increasing market share.
      Nineteen mainstream smoke constituents were evaluated. In addition, carbon
      dioxide values were obtained on all brand styles selected in 1998 and 2000.
      Collectively, the results of these surveys provide evidence that constituent
      yields are, in general, proportional to "tar" yield and that the relationships
      between constituent yields and "tar" have remained constant during this time
      span. Moreover, these data demonstrate that constituent yields of commercially
      marketed cigarettes available in the U.S. between 1995 and 2000 have been
      effectively constant.

PMID- 12052001
TI  - Chronic toxicity and carcinogenicity of sucrose fatty acid esters in Fischer
      344/DuCrj rats.
AB  - A 13-week and a 2-year feeding study were conducted in Fischer 344/DuCrj rats to
      evaluate the oral toxicity and carcinogenicity of S-570, a mixture of mono-, di-,
      tri-, and higher esters of sucrose with fatty acids derived from edible fats and
      oils. In both studies, S-570 was fed at 0, 1, 3, or 5% (w/w) of the diet to
      groups of 20 male and 20 female rats in the 13-week study and 50 male and 50
      female rats in the carcinogenicity study. Animals in satellite groups of 14
      rats/sex/group were sacrificed at 12 months to evaluate chronic toxicity. There
      were no S-570-related effects on survival, tumor incidence or time to tumor,
      ophthalmology, hematology, clinical chemistry, organ weights, or histopathology.
      These results indicate that S-570 is not toxic or carcinogenic when fed to rats
      at up to 5% of the diet for 2 years.

PMID- 12052002
TI  - Analysis of solvent central nervous system toxicity and ethanol interactions
      using a human population physiologically based kinetic and dynamic model.
AB  - The effect of acute ethanol-mediated inhibition of m-xylene metabolism on central
      nervous system (CNS) depression in the human worker population was investigated
      using physiologically based pharmacokinetic (PBPK) models and probabilistic
      random (Monte Carlo) sampling. PBPK models of inhaled m-xylene and orally
      ingested ethanol were developed and combined by a competitive enzyme (CYP2E1)
      inhibition model. Human interindividual variability was modeled by combining
      estimated statistical distributions of model parameters with the deterministic
      PBPK models and multiple random or Monte Carlo simulations. A simple threshold
      pharmacodynamic model was obtained by simulating m-xylene kinetics in human
      studies where CNS effects were observed and assigning the peak venous blood m
      xylene concentration (C(V,max)) as the dose surrogate of toxicity. Probabilistic
      estimates of an individual experiencing CNS disturbances given exposure to the
      current UK occupational exposure standard (100 ppm time-weighted average over 8
      h), with and without ethanol ingestion, were obtained. The probability of
      experiencing CNS effects given this scenario increases markedly and nonlinearly
      with ethanol dose. As CYP2E1-mediated metabolism of other occupationally relevant
      organic compounds may be inhibited by ethanol, simulation studies of this type
      should have an increasingly significant role in the chemical toxicity risk
      assessment.

PMID- 12052003
TI  - Genetic polymorphisms in assessing interindividual variability in delivered dose.
AB  - Increasing sophistication in methods used to account for human variability in
      susceptibility to toxicants has been one of the success stories in the continuing
      evolution of risk assessment science. Genetic polymorphisms have been suggested
      as an important contributor to overall human variability. Recently, data on
      polymorphisms in metabolic enzymes have been integrated with physiologically
      based pharmacokinetic (PBPK) modeling as an approach to determining the resulting
      overall variability. We present an analysis of the potential contribution of
      polymorphisms in enzymes modulating the disposition of four diverse compounds:
      methylene chloride, warfarin, parathion, and dichloroacetic acid. Through these
      case studies, we identify key uncertainties likely to be encountered in the use
      of polymorphism data and highlight potential simplifying assumptions that might
      be required to test the hypothesis that genetic factors are a substantive source
      of human variability in susceptibility to environmental toxicants. These
      uncertainties include (1) the relative contribution of multiple enzyme systems,
      (2) the extent of induction/inhibition through coexposure, (3) allelic
      frequencies of major ethnic groups, (4) the absence of chemical-specific data on
      the kinetic parameters for the different allelic forms of key enzymes, (5) large
      numbers of low-frequency alleles, and (6) uncertainty regarding differences
      between in vitro and in vivo kinetic data. Our effort sets the stage for the
      acquisition of critical data and further integration of polymorphism data with
      PBPK modeling as a means to quantitate population variability.

PMID- 12052004
TI  - Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho
      phenylphenol.
AB  - The validity of in vitro and in vivo methods for the prediction of percutaneous
      penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP)
      (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were
      performed in rats and human volunteers, applying the test compound to the dorsal
      skin and the volar aspect of the forearm, respectively. In vitro studies were
      performed using static diffusion cells with viable full-thickness skin membranes
      (rat and human), nonviable epidermal membranes (rat and human), and a perfused
      pig ear model. For the purpose of conducting in vitro/in vivo comparisons,
      standardized experimental conditions were used with respect to dose (120 microg
      OPP/cm(2)), vehicle (60% aqueous ethanol), and exposure duration (4 h). In human
      volunteers, the potentially absorbed dose (amount applied minus dislodged) was
      105 microg/cm(2), while approximately 27% of the applied dose was excreted with
      urine within 48 h. In rats these values were 67 microg/cm(2) and 40%,
      respectively. In vitro methods accurately predicted human in vivo percutaneous
      absorption of OPP on the basis of the potential absorbed dose. With respect to
      the other parameters studied (amount systemically available, maximal flux),
      considerable differences were observed between the various in vitro models. In
      viable full-thickness skin membranes, the amount systemically available and the
      potentially absorbed dose correlated reasonably well with the human in vivo
      situation. In contrast the K(p)/maximal flux considerably underestimated the
      human in vivo situation. Although epidermal membranes overestimated human in vivo
      data, the species differences observed in vivo were reflected correctly in this
      model. The data generated in the perfused pig ear model were generally
      intermediate between viable skin membranes and epidermal membranes.

PMID- 12052005
TI  - Extending the threshold of regulation concept: de minimis limits for carcinogens
      and mutagens.
AB  - Risk assessment processes for carcinogens are highly developed but risk
      assessment processes for mutagens are not well established. In the pharmaceutical
      industry, risk associated with exposure to carcinogens is tightly controlled. It
      is desirable to control risk associated with exposure to mutagens also, in spite
      of the greater uncertainty associated with the risk. In this paper, a published
      cancer potency database is used to frame the risk and to support risk management
      decisions. A de minimis exposure for mutagens is proposed and a decision matrix
      is presented to align available data with risk assessment approaches for
      carcinogens and mutagens.

PMID- 12052006
TI  - High-alumina low-silica HT stone wool fibers: a chemical compositional range with
      high biosolubility.
AB  - Man-made vitreous fibers (MMVF) are classified within the European Union (EU) as
      carcinogenic category 3 (possibly carcinogenic), but criteria exist to exonerate
      fibers from this classification. The HT stone wool fiber type is a MMVF that
      fulfills European regulatory requirements for exoneration from classification as
      a carcinogen based on in vivo testing. The chemical composition of the fibers and
      the results of the in vivo and in vitro studies that defined the chemical
      compositional range for a CAS registry number for these fibers are presented and
      discussed. Results from in vitro dissolution measurements at pH 4.5 of 52 fiber
      compositions (9-23 wt% Al(2)O(3) and 32-47 wt% SiO(2)) ranging from traditional
      stone wool to the biosoluble HT fibers are presented. The results are evaluated
      as a function of the ratio Al/(Al+Si) in the glass network and as a function of
      the fraction of Si-O-Si linkages in the glass. It is suggested that the
      dissolution mechanism for these fibers relates to the density of the surface
      silica layer on dissolving fibers and that the fraction of Si-O-Si linkages
      influences this.

PMID- 12052008
TI  - An evaluation of the possible carcinogenicity of bisphenol A to humans.
AB  - Bisphenol A (BPA) is a monomer component of polycarbonate plastics and epoxy
      resins. These resins are used in numerous consumer products, including food
      contact plastics. There has been considerable scientific debate about the
      relevance to humans of reported estrogenic actions of BPA. Much less attention
      has been focused on the carcinogenic potential of BPA. The carcinogenic potential
      of BPA was assessed through a review of metabolic data, genetic toxicity studies,
      long-term toxicity/carcinogenicity studies, and estimates of consumer exposure.
      Following a weight-of-evidence approach as recommended by IARC and U.S. EPA, it
      was concluded that BPA is not likely to be carcinogenic to humans. The bases for
      this conclusion included: (a) the results of an NTP study which provided no
      substantive evidence to indicate that BPA is carcinogenic to rodents; (b) the
      lack of activity of BPA, at noncytotoxic concentrations, in standard in vitro
      genetic toxicity tests; (c) the lack of genotoxic activity of BPA in a GLP
      compliant in vivo mouse micronucleus assay; and (d) the results of metabolism
      studies showing BPA is rapidly glucuronidated without evidence of formation of
      potentially reactive intermediates, except possibly at high doses that could
      saturate detoxication pathways. In addition, exposure assessment reveals that
      current use of BPA would result in only a trivial human exposure.

PMID- 12052007
TI  - Lack of (anti-) androgenic or estrogenic effects of three pyrethroids
      (esfenvalerate, fenvalerate, and permethrin) in the Hershberger and uterotrophic
      assays.
AB  - Synthetic pyrethroids are among the most common pesticides and insecticides
      currently in use worldwide. Recently, chemicals classified as synthetic
      pyrethroids are suspected as being endocrine disrupting chemicals. However, no
      study has been conducted to assess their potential hormonal activities using in
      vivo test specifically focused on endocrine disruption. In the present study, we
      evaluated the interaction of three pyrethroids (esfenvalerate, fenvalerate, and
      permethrin) with androgen receptor (AR)- and estrogen receptor (ER)-mediated
      mechanisms using in vivo short-term assays. While internationally standardized
      protocols for the Hershberger and uterotrophic assays have not yet been fully
      developed, both are widely used and are being considered by OECD as short-term
      screening assays for hormonal activity. A 5-day Hershberger assay using castrated
      male rats measures agonistic and androgenic ability of the test chemicals to AR
      of several accessory glands/tissues (the ventral prostate, dorsolateral prostate,
      seminal vesicles with coagulating glands, and levator ani plus bulbocavernosus
      muscles). Esfenvalerate (5, 10, or 20 mg/kg/day), fenvalerate (20, 40, or 80
      mg/kg/day), or permethrin (25, 50, or 75 mg/kg/day) was administered by oral
      gavage for 5 days to castrated male Crj:CD(SD)IGS rats (1 week after the
      castration, 11 weeks of age) with or without coadministration of 0.25 mg/kg/day
      testosterone propionate (subcutaneous injection on the dorsal surface). The
      highest dose levels tested for each chemical were considered the maximum level
      that could be used without causing excessive systemic toxicity. None of
      esfenvalerate, fenvalerate, and permethrin showed any androgenic or
      antiandrogenic effects. Reference control of p,p'-DDE and methyltestosterone (100
      mg/kg/day) provided significant effects in this assay protocol. Potential effects
      of these pyrethroids mediated through the ER were evaluated by means of 3-day
      uterotrophic assay using ovariectomized Crj:CD(SD)IGS rats (2 weeks after the
      ovariectomy, 8 weeks of age). No increase in weight of uterus (wet or blotted)
      was observed following oral exposure to esfenvalerate (5, 10, or 20 mg/kg/day),
      fenvalerate (20, 40, or 80 mg/kg/day), or permethrin (37.5, 75, or 150
      mg/kg/day), respectively. Again, the highest dose levels tested for each chemical
      were considered the maximum level that could be used without causing excessive
      systemic toxicity. Reference controls consisting of ethynyl estradiol (0.03
      mg/kg/day) and methoxychlor (125 mg/kg/day) both showed a significant effect in
      this assay protocol. It is concluded that, based on the results of these two
      reliable in vivo assays, none of esfenvalerate, fenvalerate, or permethrin
      exhibit any potential to cause adverse (anti-) androgenic or estrogenic effects
      at dose levels below that of those causing excessive systemic toxicity.

PMID- 12052009
TI  - Safety assessment of DHA-rich microalgae from Schizochytrium sp.
AB  - The purpose of this series of studies was to assess the genotoxic potential of
      docosahexaenoic acid-rich microalgae from Schizochytrium sp. (DRM). DRM contains
      oil rich in highly unsaturated fatty acids (PUFAs). Docosahexaenoic acid (DHA n
      3) is the most abundant PUFA component of the oil ( approximately 29% w/w of
      total fatty acid content). DHA-rich extracted oil from Schizochytrium sp. is
      intended for use as a nutritional ingredient in foods. All in vitro assays were
      conducted with and without mammalian metabolic activation. DRM was not mutagenic
      in the Ames reverse mutation assay using five different Salmonella histidine
      auxotroph tester strains. Mouse lymphoma suspension assay methodology was found
      to be inappropriate for this test material because precipitating test material
      could not be removed by washing after the intended exposure period and the
      precipitate interfered with cell counting. The AS52/XPRT assay methodology was
      not subject to these problems and DRM was tested and found not to be mutagenic in
      the CHO AS52/XPRT gene mutation assay. DRM was not clastogenic to human
      peripheral blood lymphocytes in culture. Additionally, DRM did not induce
      micronucleus formation in mouse bone marrow in vivo further supporting its lack
      of any chromosomal effects. Overall, the results of this series of mutagenicity
      assays support the conclusion that DRM does not have any genotoxic potential.

PMID- 12052010
TI  - Testing therapeutic potency of anticancer drugs in animal studies: a commentary.
AB  - Regulatory authorities for medicines in European countries deal with many
      applications for admission to the market of anticancer drugs. Each application
      must be supported by preclinical and clinical data, among which testing of the
      therapeutic activity of drugs in animals is important. Recently, the Committee
      for Proprietary Medicinal Products (CPMP) has released a note for guidance on the
      preclinical evaluation of anticancer medicinal products. This note provides only
      general statements regarding tests of anticancer drugs in rodents. This
      stimulates considerations on how to organize and how to evaluate these tests. In
      this article we describe our considerations regarding these items based on our
      experience with applications in The Netherlands since 1993.

PMID- 12052011
TI  - A study of the biological partitioning behavior of n-alkanes and n-alkanols in
      causing anesthetic effects.
AB  - n-Alkanes and n-alkanols are two groups of common volatile organic compounds
      (VOCs) having potential anesthetic effects on workers and building occupants. A
      partition model based on the octanol-air partition coefficient was developed in
      this investigation to describe the biological partitioning of n-alkanes and n
      alkanols in causing general anesthesia. Data on anesthetic potency (minimum
      alveolar concentration, MAC) for the test groups in rats were found to fit the
      model. The slight difference between the n-alkanes and n-alkanols in testing the
      model could be largely eliminated by correcting for the potential partial
      pressure gradients of the long-chain alkanes across the blood-brain barrier. The
      corrected MAC data for the two test groups fit well onto one common activity
      partition regression line. This suggests that n-alkanes and n-alkanols may share
      a common biophase or mechanistic pathway for anesthesia. The present findings may
      provide some useful insight into setting anesthesia-based health standards for
      VOC mixtures.

PMID- 12052012
TI  - Concept evaluation: androgen-stimulated immature intact male rats as an assay for
      antiandrogens.
AB  - The effects of the concomitant oral administration of a potent reference androgen
      (17alpha-methyltestosterone) and both a potent (flutamide) and a weak (p,p'-DDE)
      antiandrogen on intact weanling male rats are described. This protocol resulted
      in the inhibition by the antiandrogens of the increase in sex accessory tissue
      weights induced by coadministration of 17alpha-methyltestosterone. Although both
      flutamide and p,p'-DDE inhibited the androgen-induced growth of the levator
      ani/bulbocavernosus muscle complex, the Cowper's glands, and the seminal
      vesicles, the growth of the prostate gland was unaffected by either antiandrogen.
      The unresponsiveness of the prostate gland, a primary target tissue in the
      castrated rat antiandrogen assay, has yet to be fully explained. However, the
      ability of the assay to detect the activity of low dose levels of the weak
      antiandrogen DDE (at doses of 20 mg/kg body weight) makes the system worthy of
      further study as one of several alternatives. Given the rapid rate of
      assay/protocol exploration and refinement of this assay and its alternatives,
      there is the need for careful comparative studies before selecting a single
      bioassay for validation and regulatory use.

PMID- 12052014
TI  - Colorectal cancer prevention: prospects for the first decade of the 21st century.

PMID- 12052016
TI  - Page for patients. Sleep. Prev Med.

PMID- 12052015
TI  - Factors influencing intention to obtain a genetic test for colon cancer risk: a
      population-based study.
AB  - BACKGROUND: The availability of genetic testing for cancer risk has prompted an
      examination of the intention of the general public to undergo testing. This study
      expands a previous psychosocial model of factors influencing intention to undergo
      genetic testing for cancer in general to the context of colon cancer. METHODS: A
      sample of 1,836 adult residents of Vermont, New Hampshire, and Maine were
      interviewed via telephone. The survey instrument included measures derived from
      the Health Belief Model and additional psychosocial measures adapted from the
      literature. Structural Equation Modeling techniques were used to examine factors
      associated with the likelihood to undergo genetic testing. RESULTS: Perceived
      barriers and benefits of testing, and perceived susceptibility to colon cancer
      had direct associations with likelihood. Optimism and pessimism had both direct
      and indirect effects. Age, socioeconomic status, family history, and awareness of
      genetic testing had indirect effects, and acted through the other factors. The
      model explained 22% of the variance in likelihood. CONCLUSIONS: Perceived
      barriers, benefits, susceptibility, optimism, and pessimism directly influenced
      likelihood, and may also mediate the effect of background factors examined in
      this study. These findings suggest effective educational strategies to improve
      decision-making concerning genetic testing for colon cancer risk in the general
      population.

PMID- 12052017
TI  - Short-term effects of a randomized computer-based out-of-school smoking
      prevention trial aimed at elementary schoolchildren.
AB  - BACKGROUND: Smoking prevention programs usually run during school hours. In our
      study, an out-of-school program was developed consisting of a computer-tailored
      intervention aimed at the age group before school transition (11- to 12-year-old
      elementary schoolchildren). The aim of this study is to evaluate the additional
      effect of out-of-school smoking prevention. METHODS: One hundred fifty-six
      participating schools were randomly allocated to one of four research conditions:
      (a) the in-school condition, an existing seven-lesson program; (b) the out-of
      school condition, three computer-tailored letters sent to the students' homes;
      (c) the in-school and out-of-school condition, a combined approach; (d) the
      control condition. Pretest and 6 months follow-up data on smoking initiation and
      continuation, and data on psychosocial variables were collected from 3,349
      students. RESULTS: Control and out-of-school conditions differed regarding
      posttest smoking initiation (18.1 and 10.4%) and regarding posttest smoking
      continuation (23.5 and 13.1%). Multilevel logistic regression analyses showed
      positive effects regarding the out-of-school program. Significant effects were
      not found regarding the in-school program, nor did the combined approach show
      stronger effects than the single-method approaches. CONCLUSIONS: The findings of
      this study suggest that smoking prevention trials for elementary schoolchildren
      can be effective when using out-of-school computer-tailored interventions.

PMID- 12052018
TI  - Interest in BRCA1/2 testing in a primary care population.
AB  - BACKGROUND: Mutations in the breast cancer susceptibility genes BRCA1 and BRCA2
      are found in less than 1/1,000 women in the general population. Experts and
      professional organizations recommend targeting testing to women with risk factors
      for carrying a mutation. Over the next decade, BRCA1/2 testing is likely to
      become substantially less expensive and to move into primary care practice where
      pretest counseling may be limited. METHODS: The objective of the study was to
      investigate the factors associated with interest in BRCA1/2 testing among primary
      care patients receiving only limited information about testing. The design was a
      cross-sectional mailed survey. The setting was a University-based health system
      in the metropolitan Philadelphia region. The participants were 400 adult women
      cared for in a faculty General Internal Medicine practice. RESULTS: Two hundred
      forty-two women (71%) completed surveys; 53% of respondents were aware of BRCA1/2
      testing and 58% were interested in undergoing testing if it was both convenient
      and affordable. Thirty-one percent were both aware of and interested in testing.
      Awareness of testing was inversely associated with African-American race (OR
      0.56, 95% CI 0.38-0.83) and positively associated with college education (OR
      2.21, 95% CI 1.23-3.94). Interest in testing was inversely associated with a
      family history of breast cancer (OR 0.45, 95% CI 0.23-0.92) and increasing age
      (OR 0.97, 95% CI 0.95-0.99). The inverse association between family history and
      interest in testing persisted in the subgroup of women who were aware of testing
      (OR 0.55, 95% CI 0.30-0.98). CONCLUSIONS: Among a primary care population,
      African-American women are less aware of BRCA1/2 testing and, when provided only
      limited information about BRCA1/2 testing, women at lowest risk of carrying a
      mutation are most interested in undergoing BRCA1/2 testing. Challenges of moving
      BRCA1/2 testing into primary care practice include both limiting indiscriminate
      use by the "worried well" and, as proven cancer prevention strategies become
      available, ensuring access to all high-risk women regardless of race.

PMID- 12052019
TI  - Misconceptions regarding hepatitis C in the French public.
AB  - BACKGROUND: Knowing the facts and displaying the proper attitudes and behaviors
      are critical in preventing the spread of infectious diseases. Hepatitis C is a
      common infection, but the public's understanding of it has not been studied.
      METHODS: A convenience sample of 431 French adults, ages 18 to 81 years,
      completed a questionnaire designed to assess knowledge of hepatitis C and
      acquired immune deficiency syndrome. A group of nine medical experts also
      answered the hepatitis C questions. RESULTS: The lay participants had many
      uncertainties about hepatitis C, and their beliefs frequently differed from
      medical understanding about hepatitis C. Their responses were correlated more
      closely with their own responses to the AIDS questions than with the experts'
      understanding of hepatitis C. CONCLUSIONS: Information regarding hepatitis C
      should emphasize the distinctions between hepatitis C and AIDS as well as between
      hepatitis C and hepatitis B and between seropositivity and infection. People
      should also be informed that blood donation is safe, that using injected drugs is
      the main risk factor for hepatitis C, that alcohol aggravates hepatitis C, that
      hepatitis C can cause cancer, that an effective treatment for hepatitis C exists,
      and that they are not put at risk by mere causal contact with people ill with
      hepatitis C.

PMID- 12052020
TI  - Nutrition, antioxidants, and risk factor profile of nonsmokers, passive smokers
      and smokers of the Prevention Education Program (PEP) in Nuremberg, Germany.
AB  - BACKGROUND: An elevated risk for coronary artery disease and lung cancer was
      reported for smokers and nonsmokers exposed to environmental tobacco smoke.
      Particularly in nonsmokers, in addition to the adverse effects of tobacco smoke,
      other factors which are associated with the exposure to environmental tobacco
      smoke may contribute to the health risks. We investigated both by questionnaires
      and biochemical analyses whether smokers influence the dietary habits of
      nonsmokers living in the same household. METHODS: The study population was a
      subgroup of the Prevention Education Program in Nuremberg: 817 adults aged 27-66
      years were allocated to one of the four groups: Nonsmokers living with a
      nonsmoker (Group 1), nonsmokers living with a smoker (Group 2), smokers living
      with a nonsmoker (Group 3), and smokers living with a smoker (Group 4). RESULTS:
      The four groups did not differ in the body mass index, the concentration of
      lycopene, all-trans-retinol, and selenium in plasma. Plasma concentrations of
      high-density lipoprotein cholesterol, triglycerides, homocysteine, cobalamin,
      folate, beta-carotene, and alpha-tocopherol showed a gradient to unfavorable
      levels from Group 1 to Group 4. This trend was also reflected in the reported
      dietary intake of beta-carotene, alpha-tocopherol, ascorbic acid, fiber, and
      linoleic acid. CONCLUSIONS: Our data show that nonsmokers living with smokers
      indulge in less healthy dietary habits than nonsmokers living with nonsmokers.
      This has to be considered when evaluating the health risks of exposure to
      environmental tobacco smoke.

PMID- 12052021
TI  - Technical skills for weight loss: preliminary data from a randomized trial.
AB  - BACKGROUND: Optimal behavioral interventions for sustainable weight loss are
      uncertain. We therefore conducted a study among overweight/obese women comparing
      conventional dietary counseling of individuals (counseling-based intervention) to
      a novel, group-based skill-building intervention. METHODS: Eighty subjects were
      randomly assigned to either the counseling-based or to the skill-building
      intervention. Outcomes included weight loss, dietitian hours per group and per
      unit weight loss, and dollars spent per group and per unit weight lost. RESULTS:
      Weight loss at 6 months (follow-up rate 61.3%) in the counseling-based group was
      8.8 lb (P = 0.0001), and in the skill-building group was 3.8 lb (P = 0.01). A
      total of 160 dietitian hours were required for the counseling-based group, and
      131 for the skilled-building group. The counseling-based group cost an average of
      $21 per pound lost, while the skill-building cost an average of $48 per pound
      lost (P = 0.16). CONCLUSIONS: At 6 months, individualized office-based counseling
      produced more weight loss than a skill-building approach and cost less than half
      as much per pound of weight loss. Longer-term follow-up is required to determine
      if, as hypothesized, the skill-building intervention produces more sustainable
      weight loss.

PMID- 12052022
TI  - Early predictors of daily smoking in young women: the national heart, lung, and
      blood institute growth and health study.
AB  - BACKGROUND: Smoking is highly prevalent in young women and little is known about
      early multilevel independent risk or protective factors that are predictive of
      daily smoking in young women. METHODS: Multiple logistic regression was conducted
      on data from NGHS, a 10-year cohort study of Black (1,213) and White (1,166)
      girls recruited from three clinical centers in the United States, ages 9-10 years
      on entry to ages 18-19. RESULTS: Compared with never smokers, White girls were at
      higher risk than Black girls of being daily smokers at ages 18-19. Early
      predictors of daily smoking at ages 18-19 years included lower parental
      education, one parent in the household, drinking alcohol at ages 11-12, higher
      drive for thinness at ages 11-12, lower behavioral conduct at ages 11-12, and
      lower stress at ages 10-11 and higher stress at ages 12-13. For both Black and
      White girls weight-related variables were significant. Stress, behavioral
      conduct, and one-parent household were also important predictors for White girls.
      CONCLUSIONS: There is evidence that childhood and adolescent factors are related
      to young adult smoking behavior. Body weight concerns as well as family, social
      environment, and behavioral factors are important issues in determining which
      girls will become daily smokers.

PMID- 12052023
TI  - The role of smoking and rebelliousness in the development of depressive symptoms
      among a cohort of Massachusetts adolescents.
AB  - BACKGROUND: Recent studies have shown that smoking leads to depressive symptoms
      among adolescents, but the mechanisms underlying the relationship remain unclear.
      In this study, we focused on one possible mechanism, namely, the effect of
      rebelliousness. We examined the extent to which rebelliousness accounts for the
      relation between smoking and depression among adolescents in Massachusetts.
      METHODS: Data were from a follow-up telephone survey of youth in Massachusetts. A
      subset of adolescents who were classified as not highly depressed at baseline in
      1993 was used for the analyses (n = 522). Logistic regression analyses were used
      to predict whether cigarette smoking increased the odds of developing high
      depressive symptoms 4 years later, while controlling for rebelliousness and other
      factors. RESULTS: Ever smoking a cigarette at baseline had a statistically
      significant impact on high depressive symptoms at follow-up. Once rebelliousness
      was considered, the relationship between ever smoking and follow-up depressive
      symptoms became nonsignificant. CONCLUSIONS: The findings indicate that
      rebelliousness accounted for the relation between adolescent smoking and the
      emergence of depressive symptoms. Rebelliousness may provide a modifiable
      variable to be targeted to interrupt the linkage between adolescent smoking and
      depression.

PMID- 12052024
TI  - Unsafe sex, substance abuse, and domestic violence: how do recently trained
      obstetricians-gynecologists fare at lifestyle risk assessment and counseling on
      STD prevention?
AB  - BACKGROUND: Unsafe sexual practices, substance abuse, and domestic violence
      impact women's health. This study examined whether lifestyle risk assessment
      during a general medical examination and counseling about sexually transmitted
      disease during consultations for adolescent contraception and treatment of a
      sexually transmitted disease were more frequently done by recently trained
      obstetricians-gynecologists compared to those of obstetrician-gynecologists
      licensed before 1990. It also documented obstetrician-gynecologists' evaluations
      of their medical training in that area. METHODS: A pretested anonymous mail
      survey was conducted in 1995 with all 241 obstetrician-gynecologists practicing
      in Quebec, Canada; 66% responded (N = 158). RESULTS: Compared to less recently
      trained obstetrician-gynecologists, recently trained obstetrician-gynecologists
      reported routinely assessing tobacco use (77 vs 51%, P = 0.01), alcohol use (50
      vs 23%, P = 0.004), and illicit drug use (33 vs 17%, P = 0.05) more frequently
      during a patient's general medical evaluation. However, they did not assess
      condom use (50%), number of sexual partners, sexual partners' sexually
      transmitted disease risk (30%), or experiences of sexual abuse or domestic
      violence (3%) more frequently than less recently trained obstetrician
      gynecologists. They were also not more likely to counsel teenagers about sexually
      transmitted disease prevention during a contraceptive consultation (30-60%) or to
      discuss human immunodeficiency virus infection (29%) and hepatitis B immunization
      (13%) during a sexually transmitted disease consultation. CONCLUSION: Although
      evaluation of substance use was better among recently trained OB-Gyn physicians,
      little or no improvement has been noted regarding STD prevention or the
      evaluation of sexual abuse or domestic violence, all important lifestyle risks
      that directly affect women's health and well-being.

PMID- 12052025
TI  - Concomitant use of cigarettes and smokeless tobacco: prevalence, correlates, and
      predictors of tobacco cessation.
AB  - BACKGROUND: This study examined the characteristics, tobacco use patterns over
      time, and predictors of tobacco cessation among concomitant users of cigarettes
      and smokeless tobacco. METHODS: Participants were employed adults residing in the
      southeastern United States who participated in the Working Well cancer prevention
      trial. Participants were assessed at baseline and followed-up 4 years later.
      RESULTS AND CONCLUSIONS: The study yielded several key findings: (a) the
      prevalence of concomitant smoking and smokeless tobacco use was high among males
      and nonexistent among females, (b) the characteristics of concomitant users were
      relatively distinct from those of both smokers and smokeless tobacco users, (c)
      concomitant users exhibited substantial variability in their tobacco use patterns
      and were less likely to stop using tobacco than were smokers or smokeless tobacco
      users, (d) indicators of nicotine dependence predicted tobacco cessation for both
      smokers and smokeless tobacco users, but were largely unrelated to tobacco
      cessation among concomitant users, and (e) demographics, environmental variables,
      and measures derived from the transtheoretical model were not consistent
      predictors of tobacco cessation after controlling for nicotine dependence.

PMID- 12052026
TI  - School and class environments are differently linked to future smoking among
      preadolescents.
AB  - BACKGROUND: There are few observational studies of school and class risk factors
      for smoking behavior in preadolescence. METHODS: A cohort study of 2,883 children
      recruited in the fifth grade with follow-up in sixth grade was undertaken.
      Information on school and class factors was collected from principals and
      teachers of 91 schools. RESULTS: A decreased risk of smoking uptake was
      associated with exposure to short antitobacco education prior to the fifth grade
      (compared to no education). Problematic interpersonal relations in the class were
      associated with a relative risk of smoking initiation of 1.42 (confidence
      interval 1.05, 1.93) compared to positive interpersonal relations. This excess
      risk was not mediated by class smoking prevalence in the fifth grade. School
      policy and school characteristics were not significantly associated with
      preadolescents' smoking. CONCLUSIONS: Class-related, rather than school-related,
      characteristics were associated with smoking initiation and progression. Changes
      in microenvironmental factors might be useful in smoking prevention among
      preadolescents.

PMID- 12052027
TI  - Lack of experimental studies on human transmission of BSE in relation with the
      consumption of specified risk materials (SRM): the case of the milk.

PMID- 12052028
TI  - Endocannabinoids in the new millennium.

PMID- 12052029
TI  - Discovery of endocannabinoids and some random thoughts on their possible roles in
      neuroprotection and aggression.
AB  - A short history of the discovery of the main plant cannabinoid, Delta(9)
      tetrahydrocannabinol and of the endogenous cannabinoids anandamide, 2
      arachidonoyl glycerol and 2-arachidonyl glyceryl ether (noladin ether) is
      presented. The role of the cannabinoids in neuroprotection, with emphasis on the
      endocannabinoids, is described. The unexpected production of aggression by
      Cannabis and cannabinoids under stressful conditions, published mainly in the
      past, is summarized.

PMID- 12052030
TI  - Cannabinoid receptors and their ligands.
AB  - There are at least two types of cannabinoid receptors, CB(1) and CB(2), both
      coupled to G proteins. CB(1) receptors exist primarily on central and peripheral
      neurons, one of their functions being to modulate neurotransmitter release. CB(2)
      receptors are present mainly on immune cells. Their roles are proving more
      difficult to establish but seem to include the modulation of cytokine release.
      Endogenous agonists for cannabinoid receptors (endocannabinoids) have also been
      discovered, the most important being arachidonoyl ethanolamide (anandamide), 2
      arachidonoyl glycerol and 2-arachidonyl glyceryl ether. Other endocannabinoids
      and cannabinoid receptor types may also exist. Although anandamide can act
      through CB(1) and CB(2) receptors, it is also a vanilloid receptor agonist and
      some of its metabolites may possess yet other important modes of action. The
      discovery of the system of cannabinoid receptors and endocannabinoids that
      constitutes the "endocannabinoid system" has prompted the development of CB(1)-
      and CB(2)-selective agonists and antagonists/inverse agonists. CB(1)/CB(2)
      agonists are already used clinically, as anti-emetics or to stimulate appetite.
      Potential therapeutic uses of cannabinoid receptor agonists include the
      management of multiple sclerosis/spinal cord injury, pain, inflammatory
      disorders, glaucoma, bronchial asthma, vasodilation that accompanies advanced
      cirrhosis, and cancer. Following their release onto cannabinoid receptors,
      endocannabinoids are removed from the extracellular space by membrane transport
      and then degraded by intracellular enzymic hydrolysis. Inhibitors of both these
      processes have been developed. Such inhibitors have therapeutic potential as
      animal data suggest that released endocannabinoids mediate reductions both in
      inflammatory pain and in the spasticity and tremor of multiple sclerosis. So too
      have CB(1) receptor antagonists, for example for the suppression of appetite and
      the management of cognitive dysfunction or schizophrenia.

PMID- 12052031
TI  - Molecular biology of cannabinoid receptors.
AB  - During the last decade, research on the molecular biology and genetics of
      cannabinoid receptors has led to a remarkable progress in understanding of the
      endogenous cannabinoid system, which functions in a plethora of physiological
      processes in the animal. At present, two types of cannabinoid receptors have been
      cloned from many vertebrates, and three endogenous ligands (the endocannabinoids
      arachidonoyl ethanolamide, 2-arachidonoyl glycerol and 2-arachidonoyl-glycerol
      ether) have been characterized. Cannabinoid receptor type 1 (CB(1)) is expressed
      predominantly in the central and peripheral nervous system, while cannabinoid
      receptor type 2 (CB(2)) is present almost exclusively in immune cells.
      Cannabinoid receptors have not yet been cloned from invertebrates, but binding
      proteins for endocannabinoids, endocannabinoids and metabolic enzyme activity
      have been described in a variety of invertebrates except for molting
      invertebrates such as Caenorhabditis elegans and Drosophila. In the central
      nervous system of mammals, there is strong evidence emerging that the CB(1) and
      its ligands comprise a neuromodulatory system functionally interacting with other
      neurotransmitter systems. Furthermore, the presynaptic localization of CB(1)
      together with the results obtained from electrophysiological experiments
      strengthen the notion that in cerebellum and hippocampus and possibly in other
      regions of the central nervous system, endocannabinoids may act as retrograde
      messengers to suppress neurotransmitter release at the presynaptic site. Many
      recent studies using genetically modified mouse lines which lack CB(1) and/or
      CB(2) finally could show the importance of cannabinoid receptors in animal
      physiology and will contribute to unravel the full complexity of the cannabinoid
      system.

PMID- 12052032
TI  - Endocannabinoid structure-activity relationships for interaction at the
      cannabinoid receptors.
AB  - Anandamide (N -arachidonoylethanolamine) was the first ligand to be identified as
      an endogenous ligand of the G-protein coupled cannabinoid CB1 receptor.
      Subsequently, two other fatty acid ethanolamides, N -homo- gamma 
      linolenylethanolamine and N -7,10,13,16-docosatetraenylethanolamine were
      identified as endogenous cannabinoid ligands. A fatty acid ester, 2
      arachidonoylglycerol (2-AG), and a fatty acid ether, 2-arachidonyl glyceryl ether
      also have been isolated and shown to be endogenous cannabinoid ligands. Recent
      studies have postulated the existence of carrier-mediated anandamide transport
      that is essential for termination of the biological effects of anandamide. A
      membrane bound amidohydrolase (fatty acid amide hydrolase, FAAH), located
      intracellularly, hydrolyzes and inactivates anandamide and other endogenous
      cannabinoids such as 2-AG. 2-AG has also been proposed to be an endogenous CB2
      ligand. Structure-activity relationships (SARs) for endocannabinoid interaction
      with the CB receptors are currently emerging in the literature. This review
      considers cannabinoid receptor SAR developed to date for the endocannabinoids
      with emphasis upon the conformational implications for endocannabinoid
      recognition at the cannabinoid receptors.

PMID- 12052033
TI  - CB(1) and CB(2) receptor-mediated signalling: a focus on endocannabinoids.
AB  - The discovery that the major psychoactive component of marijuana activated two G
      protein coupled receptors prompted the search for the endogenous cannabinoid
      ligands now termed endocannabinoids. To date three putative ligands have been
      isolated, all consisting of arachidonic acid linked to a polar head group. Both
      synthetic and endogenous cannabinoids have been the focus of extensive study over
      the past few years. The signalling events produced by endocannabinoids as
      compared with Delta(9) -THC and synthetic cannabinoids contain many similarities.
      However, as research focuses more on endogenous ligands the divergence between
      these classes of compounds grows. This review focuses upon the developments in
      endocannabinoid signal transduction from receptor-mediated activation of common G
      protein linked effector pathways through downstream regulation of gene
      transcription.

PMID- 12052034
TI  - Biosynthesis and degradation of anandamide and 2-arachidonoylglycerol and their
      possible physiological significance.
AB  - N -arachidonoylethanolamine (anandamide) was the first endogenous cannabinoid
      receptor ligand to be discovered. Dual synthetic pathways for anandamide have
      been proposed. One is the formation from free arachidonic acid and ethanolamine,
      and the other is the formation from N -arachidonoyl phosphatidylethanolamine (PE)
      through the action of a phosphodiesterase. These pathways, however, do not appear
      to be able to generate a large amount of anandamide, at least under physiological
      conditions. The generation of anandamide from free arachidonic acid and
      ethanolamine is catalyzed by a degrading enzyme anandamide amidohydrolase/fatty
      acid amide hydrolase operating in reverse and requires large amounts of
      substrates. As for the second pathway, arachidonic acids esterified at the 1
      position of glycerophospholipids, which are mostly esterified at the 2-position,
      are utilized for the formation of N -arachidonoyl PE, a stored precursor form of
      anandamide. In fact, the actual levels of anandamide in various tissues are
      generally low except in a few cases. 2-Arachidonoylglycerol (2-AG) was the second
      endogenous cannabinoid receptor ligand to be discovered. 2-AG is a degradation
      product of arachidonic acid-containing glycerophospholipids such as inositol
      phospholipids. Several investigators have demonstrated that 2-AG is produced in a
      variety of tissues and cells upon stimulation. 2-AG acts as a full agonist at the
      cannabinoid receptors (CB1 and CB2). Evidence is gradually accumulating and
      indicates that 2-AG is the most efficacious endogenous natural ligand for the
      cannabinoid receptors. In this review, we summarize the tissue levels,
      biosynthesis, degradation and possible physiological significance of two
      endogenous cannabimimetic molecules, anandamide and 2-AG.

PMID- 12052035
TI  - Cellular transport of anandamide, 2-arachidonoylglycerol and
      palmitoylethanolamide--targets for drug development?
AB  - The endogenous cannabinoid anandamide (AEA) is transported into cells by a
      temperature-sensitive process of facilitated diffusion. This uptake process has
      been characterised both biochemically and pharmacologically, and shown to be
      regulated at least in part by the intracellular metabolism of the accumulated AEA
      by fatty acid amide hydrolase. In this review, the properties of this transport
      process are briefly reviewed together with the corresponding transport mechanisms
      for the related endogenous compounds 2-arachidonoylglycerol and
      palmitoylethanolamide. In addition, the possibility that these transport
      mechanisms can be targets for therapeutic strategies aimed at prolonging the
      effects of the endocannabinoids is discussed.

PMID- 12052036
TI  - The fatty acid amide hydrolase (FAAH).
AB  - The fatty acid amide hydrolase (FAAH), is the enzyme responsible for the
      hydrolysis of anandamide, an endocannabinoid. The FAAH knockout, the assays for
      FAAH, the activity of its substrates, its reversibility and its cloning from rat,
      mouse, human, and pig are covered in this review. The conserved regions of FAAH
      are described in terms of sequence and function, including the domains that
      contains the serine catalytic nucleophile, the hydrophobic domain important for
      self-association, the proline rich domain region which may be important for
      subcellular localization and the fatty acid chain binding domain. The FAAH mouse
      promoter region was characterized in terms of its transcription start site and
      its activity in different cell types. The distribution of FAAH in the major
      organs in the body is described as well as regional distribution in the brain and
      its correlation with cannabinoid receptors. Since FAAH is recognized as a drug
      target, a large number of inhibitors have been synthesized and tested since 1994
      and these are reviewed in terms of reversibility, potency, and specificity for
      FAAH.

PMID- 12052037
TI  - Oxidative metabolism of endocannabinoids.
AB  - There is increasing evidence that endocannabinoids play roles in a number of
      physiological and pathological processes ranging from the regulation of food
      intake to the inhibition of cancer cell proliferation. Consequently, multiple
      investigations into endocannabinoid metabolic disposition have been initiated.
      Such studies have begun to shed light on the mechanisms that regulate the
      endogenous cannabinoid system. In addition, they have identified a number of
      novel, endocannabinoid-derived lipids. In the future, these studies may form the
      foundation of efforts designed to subtly manipulate endocannabinoid tone in vivo
      to achieve therapeutic benefits without the profound side-effects observed with
      synthetic cannabinoid treatment. In addition to the well-studied hydrolytic mode
      of endocannabinoid metabolism, accumulating data suggest that these lipids are
      also susceptible to oxidative metabolism by a number of fatty acid oxygenases.
      These include the cyclooxygenases, lipoxygenases, and cytochrome P450s known to
      be involved in eicosanoid production from arachidonic acid. The available
      evidence concerning endocannabinoid oxidation is reviewed and the potential
      biological significance of this mode of metabolism is considered.

PMID- 12052038
TI  - Endocannabinoids in the central nervous system--an overview.
AB  - Many aspects of the physiology and pharmacology of anandamide (arachidonoyl
      ethanol amide), the first endogenous cannabinoid ligand ("endocannabinoid")
      isolated from pig brain, have been studied since its discovery in 1992. Ethanol
      amides from other fatty acids have also been identified as endocannabinoids with
      similar in vivo and in vitro pharmacological properties. 2-Arachidonoyl glycerol
      and noladin ether (2-arachidonyl glyceryl ether), isolated in 1995 and 2001,
      respectively, so far, display pharmacological properties in the central nervous
      system, similar to those of anandamide. The endocannabinoids are widely
      distributed in brain, they are synthesized and released upon neuronal
      stimulation, undergo reuptake and are hydrolyzed intracellularly by fatty acid
      amide hydrolase (FAAH). For therapeutic purposes, inhibitors of FAAH may provide
      more specific cannabinoid activities than direct agonists, and several such
      molecules have already been developed. Pharmacological effects of the
      endocannabinoids are very similar, yet not identical, to those of the plant
      derived and synthetic cannabinoid receptor ligands. In addition to
      pharmacokinetic explanations, direct or indirect interactions with other
      receptors have been considered to explain some of these differences, including
      activities at serotonin and GABA receptors. Binding affinities for other
      receptors such as the vanilloid receptor, have to be taken into account in order
      to fully understand endocannabinoid physiology. Moreover, possible interactions
      with receptors for the lysophosphatidic acids deserve attention in future
      studies. Endocannabinoids have been implicated in a variety of physiological
      functions. The areas of central activities include pain reduction, motor
      regulation, learning/memory, and reward. Finally, the role of the endocannabinoid
      system in appetite stimulation in the adult organism, and perhaps more
      importantly, its critical involvement in milk ingestion and survival of the
      newborn, may not only further our understanding of the physiology of food intake
      and growth, but may also find therapeutic applications in wasting disease and
      infant's "failure to thrive".

PMID- 12052039
TI  - Endocannabinoids in pain modulation.
AB  - Five major approaches have been employed to determine the role of
      endocannabinoids in pain modulation: (1) studies of various markers of
      endocannabinoid action aimed at determining whether the necessary cannabinoid
      biochemical machinery is present in those brain areas that control pain
      sensitivity; (2) administration of exogenous cannabinoids to determine whether
      endocannabinoid action at appropriate sites would lead to a loss of pain
      sensitivity; (3) administration of compounds that would affect endocannabinoid
      action such as antagonists and transport inhibitors to determine whether drug
      induced preterbation of cannabinoid action would alter pain sensitivity; (4)
      studies of genetically altered animals aimed at determining whether pain
      responses or responses to cannabinergic drugs are altered; and (5) studies that
      measure the release of endocannabinoids. Converging evidence from each of these
      research areas indicates that endocannabinods function to control pain in
      parallel with endogenous opioids but via different mechanisms.

PMID- 12052040
TI  - Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and
      neuropathy.
AB  - Analgesia is an important physiological function of the endocannabinoid system
      and one of significant clinical relevance. This review discusses the analgesic
      effects of endocannabinoids at spinal and peripheral levels, firstly by
      describing the physiological framework for analgesia and secondly by reviewing
      the evidence for analgesic effects of endocannabinoids obtained using animal
      models of clinical pain conditions. In the spinal cord, CB(1) receptors have been
      demonstrated in laminae of the dorsal horn intimately concerned with the
      processing of nociceptive information and the modulation thereof. Similarly,
      CB(1) receptors have been demonstrated on the cell bodies of primary afferent
      neurones; however, the exact phenotype of cells which express this receptor
      requires further elucidation. Local administration, peptide release and
      electrophysiological studies support the concept of spinally mediated
      endocannabinoid-induced analgesia. Whilst a proportion of the peripheral
      analgesic effect of endocannabinoids can be attributed to a neuronal mechanism
      acting through CB(1) receptors expressed by primary afferent neurones, the
      antiinflammatory actions of endocannabinoids, mediated through CB(2) receptors,
      also appears to contribute to local analgesic effects. Possible mechanisms of
      this CB(2)-mediated effect include the attenuation of NGF-induced mast cell
      degranulation and of neutrophil accumulation, both of which are processes known
      to contribute to the generation of inflammatory hyperalgesia. The analgesic
      effects of cannabinoids have been demonstrated in models of somatic and visceral
      inflammatory pain and of neuropathic pain, the latter being an important area of
      therapeutic need. Analgesia is one of the principal therapeutic targets of
      cannabinoids. This review will discuss the analgesic effects of endocannabinoids
      in relation to two areas of therapeutic need, persistent inflammation and
      neuropathic pain. The more general aspects of the role of cannabinoids,
      endogenous and exogenous, in analgesia have been recently reviewed elsewhere
      (Rice, Curr Opi Invest Drugs 2001; 2: 399-414; Pertwee, Prog Neurobil 2001; 63:
      569-611; Rice, Mackie, In: Evers A. S, ed. Anesthetic Pharmacology: Physiologic
      Principles and Clinical Practice. St. Louis: Harcourt Health Sciences, 2002).
      Since a major goal in the development of cannabinoid-based analgesics is to
      divorce the antinociceptive effects from the psychotrophic effects, the
      discussion will focus on the antinociceptive effects produced at the spinal cord
      and/or peripheral level as these areas are the most attractive targets in this
      regard. A mechanistic discussion of the "framework" for analgesia will be
      followed by a description of studies examining the role of endocannabinoids in
      relieving pain; since the elucidation of these effects was undertaken using
      synthetic cannabinoids, reference will also be made to such studies, in the
      context of endocannabinoids.

PMID- 12052041
TI  - Endocannabinoids and basal ganglia functionality.
AB  - In recent years, our knowledge on the cannabinoid pharmacology has shown a
      significant rise in terms of both quantity (more compounds and more targets) and
      quality (more selective compounds). This allows to consider cannabinoids and
      related compounds as a promising new line of research for therapeutic treatment
      of a variety of conditions, such as brain injury, chronic pain, glaucoma, asthma,
      cancer and AIDS-associated effects and other pathologies. Motor disorders are
      another promising field for the therapeutic application of cannabinoid-related
      compounds, since the control of movement is one of the more relevant
      physiological roles of the endocannabinoid transmission in the brain. There are
      two pathologies, Parkinson's disease and Huntington's chorea, which are
      particularly interesting from a clinical point of view due to the direct
      relationship of endocannabinoids and their receptors with neurons that degenerate
      in those disorders. However, other neurological pathologies, such as Alzheimer's
      disease or multiple sclerosis, which are not motor disorders in origin, but
      present a strong alteration in the control of movement, have also been a subject
      of interesting research for a cannabinoid therapy. This review will summarize our
      current knowledge on the role of these endogenous substances in the control of
      movement and, in particular, on the possible therapeutic usefulness of these
      compounds in the treatment of motor pathologies.

PMID- 12052042
TI  - Endocannabinoids in cognition and dependence.
AB  - Cannabis use is associated with a wide range of pharmacological effects, some of
      which have potential therapeutic benefit while others result in negative
      outcomes. Acute cannabinoid intoxication has been well documented to produce
      deficits in cognitive functioning with concomitant changes in glutamatergic,
      GABAergic, and cholinergic neurochemical systems in the hippocampus, each of
      which has been implicated in memory. Additionally, cannabis-dependent individuals
      abstaining from this drug can undergo a constellation of mild withdrawal effects.
      The use of the CB(1) cannabinoid receptor antagonist SR141716A and transgenic
      mice lacking the CB(1) receptor are critical tools for investigating the role of
      the endocannabinoid system in cognition, drug dependence, and other physiological
      processes. Converging evidence in which performance in a variety of memory tasks
      is enhanced following either SR141716A treatment or in CB(1) receptor knockout
      mice indicates that this system may play an important role in modulating
      cognition. There are also indications that this system may function to modulate
      opioid dependence. The purpose of this review is to describe recent advances that
      have furthered our understanding of the roles that the endocannabinoid system
      play on both cognition and drug dependence.

PMID- 12052043
TI  - Neuromodulatory role of the endocannabinoid signaling system in alcoholism: an
      overview.
AB  - The current review evaluates the evidence that some of the pharmacological and
      behavioral effects of ethanol (EtOH), including EtOH-preferring behavior, may be
      mediated through the endocannabinoid signaling system. The recent advances in the
      understanding of the neurobiological basis of alcoholism suggest that the
      pharmacological and behavioral effects of EtOH are mediated through its action on
      neuronal signal transduction pathways and ligand-gated ion channels, receptor
      systems, and receptors that are coupled to G-proteins. The identification of a G
      protein-coupled receptor, namely, the cannabinoid receptor (CB1 receptor) that
      was activated by Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major
      psychoactive component of marijuana, led to the discovery of endogenous
      cannabinoid agonists. To date, two fatty acid derivatives identified to be
      arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) have been isolated
      from both nervous and peripheral tissues. Both these compounds have been shown to
      mimic the pharmacological and behavioral effects of Delta(9)-THC. The involvement
      of the endocannabinoid signaling system in the development of tolerance to the
      drugs of abuse including EtOH has not been known until recently. Recent studies
      from our laboratory have demonstrated for the first time the down-regulation of
      CB1 receptor function and its signal transduction by chronic EtOH. The observed
      down-regulation of CB1 receptor binding and its signal transduction results from
      the persistent stimulation of the receptors by the endogenous CB1 receptor
      agonists, AEA and 2-AG, the synthesis of which has been found to be increased by
      chronic EtOH treatment. This enhanced formation of endocannabinoids may
      subsequently influence the release of neurotransmitters. It was found that the
      DBA/2 mice, known to avoid EtOH intake, have significantly reduced brain-CB1
      receptor function consistent with other studies, where the CB1 receptor
      antagonist SR141716A has been shown to block voluntary EtOH intake in rodents.
      Similarly, activation of the CB1 receptor system promoted alcohol craving,
      suggesting a role for the CB1 receptor gene in excessive EtOH drinking behavior
      and development of alcoholism. Ongoing investigations may lead to the development
      of potential therapeutic strategies for the treatment of alcoholism.

PMID- 12052044
TI  - The role of endocannabinoids in the hypothalamic regulation of visceral function.
AB  - The hypothalamus plays an important role in the regulation of several visceral
      processes, including food intake, thermoregulation and control of anterior
      pituitary secretion. Endogenous cannabinoids and CB(1) cannabinoid receptors have
      been found in the hypothalamus. In the present review, we would like to clarify
      the role of the endocannabinoid system in the regulation of the above-mentioned
      visceral functions. There is historical support for the role of marihuana (i.e.
      exogenous cannabinoids) in the regulation of appetite. Endocannabinoids also
      stimulate food intake. Furthermore, the specific CB(1) receptor antagonist
      SR141716 reduces food intake. Leptin treatment decreases endocannabinoid levels
      in normal rats and ob/ob mice. These findings provide evidence for the role of
      the hypothalamic endocannabinoid system in food intake and appetite regulation.
      Cannabinoids can change body temperature in a dose-dependent manner. High doses
      cause hypothermia while low doses cause hyperthermia. Cannabinoid administration
      decreases heat production. It seems that the effects of can- nabinoids on
      thermoregulation is exerted by altering some neurochemical mediator effects at
      both the presynaptic and postsynaptic level.THC and endocannabinoids have mainly
      inhibitory effects on the regulation of reproduction. Administration of
      anandamide (AEA) decreases serum luteinizing hormone (LH) and prolactin (PRL)
      levels. AEA causes a prolongation of pregnancy in rats and temporarily inhibits
      the postnatal development of the hypothalamo-pituitary axis in offspring. The
      action of AEA on the reproductory parameters occurs at both the hypothalamic and
      pituitary level. CB(1) receptors have also been found in the anterior pituitary.
      Further, LH levels in CB(1) receptor-inactivated mice were decreased compared
      with wild-type mice. Taken together, all these observations suggest that the
      endocannabinoid system is playing an important part in the regulation of the
      mentioned visceral functions and it provides the bases for further applications
      of cannabinoid receptor agonists and/or antagonists in visceral diseases
      regulated by the hypothalamus.

PMID- 12052045
TI  - Endocannabinoids, hormone-cytokine networks and human fertility.
AB  - Anandamide (N -arachidonoylethanolamine, AEA) is a major endocannabinoid, shown
      to impair mouse pregnancy and embryo development and to induce apoptosis in
      blastocysts. Here, we review the roles of AEA, of the AEA-binding cannabinoid
      (CB) receptors, of the selective AEA membrane transporter (AMT), and of the AEA
      hydrolyzing enzyme fatty acid amide hydrolase (FAAH), in human gestation. In
      particular, we discuss the interplay between the endocannabinoid system and the
      hormone-cytokine array involved in the control of human pregnancy, showing that
      the endocannabinoids take part in the immunological adaptation occurring during
      early pregnancy. In this line, we discuss the critical role of FAAH in human
      peripheral lymphocytes, showing that the expression of this enzyme is regulated
      by progesterone, Th1 and Th2 cytokines, which also regulate fertility. Moreover,
      we show that AEA and the other endocannabinoid, 2-arachidonoylglycerol, inhibit
      the release of the fertility-promoting cytokine leukemia inhibitory factor from
      human lymphocytes. Taken together, low FAAH and consistently high blood levels of
      AEA, but not CB receptors or AMT, can be early (<8 weeks of gestation) markers of
      spontaneous abortion, potentially useful as diagnostic tools for large-scale,
      routine monitoring of gestation in humans.

PMID- 12052046
TI  - Endocannabinoids in the immune system and cancer.
AB  - The present review focuses on the role of the endogenous cannabinoid system in
      the modulation of immune response and control of cancer cell proliferation. The
      involvement of cannabinoid receptors, endogenous ligands and enzymes for their
      biosynthesis and degradation, as well as of cannabinoid receptor-independent
      events is discussed. The picture arising from the recent literature appears very
      complex, indicating that the effects elicited by the stimulation of the
      endocannabinoid system are strictly dependent on the specific compounds and cell
      types considered. Both the endocannabinoid anandamide and its congener
      palmitoylethanolamide, exert a negative action in the onset of a variety of
      parameters of the immune response. However, 2-arachidonoylglycerol appears to be
      the true endogenous ligand for peripheral cannabinoid receptors, although its
      action as an immunomodulatory molecule requires further characterization.
      Modulation of the endocannabinoid system interferes with cancer cell
      proliferation either by inhibiting mitogenic autocrine/paracrine loops or by
      directly inducing apoptosis; however, the proapoptotic effect of anandamide is
      not shared by other endocannabinoids and suggests the involvement of non
      cannabinoid receptors, namely the VR1 class of vanilloid receptors. In
      conclusion, further investigations are needed to elucidate the function of
      endocannabinoids as immunosuppressant and antiproliferative/cytotoxic agents. The
      experimental evidence reviewed in this article argues in favor of the therapeutic
      potential of these compounds in immune disorders and cancer.

PMID- 12052047
TI  - Endocannabinoids and the gut.
AB  - In the digestive tract, there is evidence for the presence of high amounts of
      endocannabinoids (anandamide and 2-arachidonylglycerol) and of mechanisms for
      endocannabinoid metabolism and possibly endocannabinoid uptake. Pharmacological
      studies have shown that anandamide inhibits excitatory transmission and
      peristalsis in the isolated guinea-pig ileum and reduces intestinal motility in
      the mouse in vivo; all these effects are mediated by CB(1) receptors, which are
      located on enteric nerves. Conversely, the selective CB(1) receptor antagonist
      SR141716A increased intestinal motility and this effect is likely due to the
      displacement of endocannabinoids rather than to its inverse agonist properties.
      Interestingly, inhibitory effects of anandamide via non-CB(1) receptors and
      stimulatory effects via vanilloid receptors have also been proposed.

PMID- 12052048
TI  - Cardiovascular pharmacology of anandamide.
AB  - The fatty acid amide anandamide produces hypotension and a decrease in systemic
      vascular resistance in vivo. A drop in blood pressure is also seen with synthetic
      cannabinoid (CB) receptor agonists. The hypotensive responses to anandamide and
      synthetic cannabinoids are absent in CB1 receptor gene knockout mice. In isolated
      arteries and perfused vascular beds, anandamide induces vasodilator responses,
      which cannot be mimicked by synthetic cannabinoids. Instead, vanilloid receptors
      on perivascular sensory nerves play a key role in these effects of anandamide.
      Activation of vanilloid receptors by anandamide triggers the release of sensory
      neuropeptides such as the vasodilator calcitonin gene-related peptide (CGRP).
      Anandamide is detected in blood and in many cells of the cardiovascular system,
      and macrophage-derived anandamide may be involved in several hypotensive clinical
      conditions. Interestingly, cannabinoid and vanilloid receptors display an overlap
      in ligand recognition properties, and the frequently used CB1 receptor antagonist
      SR141716A also inhibits vanilloid receptor-mediated responses. The presence of
      anandamide in endothelial cells, neurones and activated macrophages (monocytes),
      and its ability to activate CB and vanilloid receptors make this lipid a
      potential bioregulator in the cardiovascular system.

PMID- 12052049
TI  - The endocannabinoid system in invertebrates.
AB  - What is the role of the cannabinoid system in invertebrates and can it tell us
      something about the human system? We discuss in this review the possible presence
      of the cannabinoid system in invertebrates. Endocannabinoid processes, i.e.,
      enzymatic hydrolysis, as well as cannabinoid receptors and endocannabinoids, have
      been identified in various species of invertebrates. These signal molecules
      appear to have multiple roles in invertebrates; diminishing sensory input,
      control of reproduction, feeding behavior, neurotransmission and antiinflammatory
      actions. We propose that since this system worked so well, it was retained during
      evolution, and that invertebrates can serve as a model to study endogenous
      cannabinoid signaling.

PMID- 12052050
TI  - Cannabinoid receptor-inactive N-acylethanolamines and other fatty acid amides:
      metabolism and function.
AB  - Although it is now generally accepted that long-chain N-acylethanolamines and
      their precursors, N-acylethanolamine phospholipids, exist as trace constituents
      in virtually all vertebrate cells and tissues, their possible biological
      functions are just emerging. While anandamide (N-arachidonoylethanolamine) has
      received much attention due to its ability to bind to and activate cannabinoid
      receptors, the saturated and monounsaturated N-acylethanolamines, which usually
      represent the vast majority, are cannabinoid receptor-inactive but appear to
      interact with endocannabinoids and to have other signaling functions as well.
      Also, primary fatty acid amides, including the amide of oleic acid, which acts as
      a sleep-inducing agent, do not interact with cannabinoid receptors but are
      catabolically related to endocannabinoids. Here we review published information
      on the occurrence, metabolism, and possible signaling functions of the
      cannabinoid receptor-inactive N-acylethanolamines and primary fatty acid amides.

PMID- 12052051
TI  - Anandamide receptors.
AB  - Anandamide (N -arachidonoyl-ethanolamine, AEA) was the first endogenous ligand of
      cannabinoid receptors to be discovered. Yet, since early studies, AEA appeared to
      exhibit also some effects that were not mediated by cannabinoid CB(1) or CB(2)
      receptors. Indeed, AEA exerts some behavioral actions also in mice with
      genetically disrupted CB(1) receptors, whereas in vitro it is usually a partial
      agonist at these receptors and a weak activator of CB(2) receptors. Nevertheless,
      several pharmacological effects of AEA are mediated by CB(1) receptors, which, by
      being coupled to G-proteins, can be seen as AEA "metabotropic" receptors.
      Furthermore, at least two different, and as yet uncharacterized, G-protein
      coupled AEA receptors have been suggested to exist in the brain and vascular
      endothelium, respectively. AEA is also capable of directly inhibiting ion
      currents mediated by L-type Ca(2+) channels and TASK-1 K(+) channels. However, to
      date the only reasonably well characterized, non-cannabinoid site of action for
      AEA is the vanilloid receptor type 1 (VR1), a non-selective cation channel gated
      also by capsaicin, protons and heat. VR1 might be considered as an AEA
      "ionotropic" receptor and, under certain conditions, mediates effects ranging
      from vasodilation, broncho-constriction, smooth muscle tone modulation and
      nociception to stimulation of hippocampal pair-pulse depression, inhibition of
      tumor cell growth and induction of apoptosis.

PMID- 12052052
TI  - Directed evolution of N-carbamyl-D-amino acid amidohydrolase for simultaneous
      improvement of oxidative and thermal stability.
AB  - Directed evolution of N-carbamyl-D-amino acid amidohydrolase from Agrobacterium
      tumefaciens NRRL B11291 was attempted in order to simultaneously improve
      oxidative and thermal stability. A mutant library was generated by DNA shuffling,
      and positive clones with improved oxidative and thermal stability were screened
      on the basis of the activity staining method on a solid agar plate containing pH
      indicator (phenol red) and substrate (N-carbamyl-D-p-hydroxyphenylglycine). Two
      rounds of directed evolution resulted in the best mutant 2S3 with a significantly
      improved stability. Oxidative stability of the evolved enzyme 2S3 was about 18
      fold higher than that of the wild type, and it also showed an 8-fold increased
      thermostability. The K(m) value of 2S3 was comparable to that of wild-type
      enzyme, but k(cat) was slightly decreased. DNA sequence analysis revealed that
      six amino acid residues (Q23L, V40A, H58Y, G75S, M184L, and T262A) were
      substituted in 2S3. From the mutational analysis, four mutations (Q23L, H58Y,
      M184L, and T262A) were found to lead to an improvement of both oxidative and
      thermal stability. Of them, T262A had the most significant effect, and V40A and
      G75S only increased the oxidative stability.

PMID- 12052053
TI  - Improved paclitaxel and baccatin III production in suspension cultures of Taxus
      media.
AB  - A cell suspension culture of Taxus media was established from a stable callus
      line of this species. The growth rate and production of paclitaxel and baccatin
      III of this cell suspension were significantly increased during the shake flask
      culture in its respective optimum media for cell growth and product formation,
      which were selected after assaying 24 different culture media. The highest yields
      of paclitaxel (2.09 mg L(-1)) and baccatin III (2.56 mg L(-1)) in the production
      medium rose (factors of 7.0 and 3.0, respectively) in the presence of
      methyljasmonate (220 microg g(-1) FW). When the elicitor was added together with
      mevalonate (0.38 mM) and N-benzoylglycine (0.2 mM), the increase in the yields of
      paclitaxel and baccatin III was even higher (factors of 8.3 and 4.0,
      respectively). Thereafter, a two-stage culture for cell suspension was carried
      out using a 5-l stirred bioreactor running for 36 days, the first stage being in
      the cell growth medium until cells entered their stationary growth phase (12
      days) and the second stage being in the production medium supplemented with the
      elicitor and two putative precursors in the concentrations indicated above. Under
      these conditions, 21.12 mg L(-1) of paclitaxel and 56.03 mg L(-1) of baccatin III
      were obtained after 8 days of culture in the production medium.

PMID- 12052054
TI  - Synthesis of water-soluble retinol derivatives by enzymatic method.
AB  - Retinoids (vitamin A and derivatives) are of great commercial potential in
      cosmetics and pharmaceuticals such as skin care products. However, the clinical
      effectiveness of these retinoids is limited by skin irritation, water
      insolubility, and except for retinyl-esters, extreme instability. In this paper,
      an enzymatic method for preparing water-soluble retinol derivatives catalyzed by
      immobilized lipase is described. The synthesis is based on a unique strategy of
      two-step enzymatic acylation. Among the different synthesized compounds, the most
      water-soluble are the disaccharide derivatives such as saccharose retinyl adipate
      (nonionic water-soluble retinol derivative) and the sodium salt of retinyl
      diacids such as retinyl succinate sodium salt (ionic water-soluble retinol
      derivative).

PMID- 12052055
TI  - Enhanced-rate biodegradation of organophosphate neurotoxins by immobilized
      nongrowing bacteria.
AB  - Pesticide wastes generated from livestock dipping operations containing the
      organophosphate (OP) insecticide coumaphos (CP) are well suited for disposal by
      biodegradation since they are highly concentrated (approximately 1 g/L),
      generally contained, and lack additional toxic components. In this study, a
      significantly enhanced efficiency of degrading CP in cattle dip waste (CDW) is
      reported using a dense, nongrowing cell population that functions without the
      addition of nutrients required for growing cell cultures. A recombinant strain of
      Escherichia coli containing the opd gene for organophosphate hydrolase (OPH),
      which is capable of active hydrolysis of OP neurotoxins including CP, was
      cultivated in a rich medium containing all essential nutrients. Cells were
      harvested and utilized in lab scale experiments in the form of either freely
      suspended cells or cells immobilized within a macroporous gel matrix, poly(vinyl
      alcohol) (PVA) cryogel. Significantly higher degradation rates were achieved with
      either suspended or immobilized OPH(+) cells compared to rates with the microbial
      consortium naturally present in CDW. Of the two nongrowing cell systems, the
      detoxification rate with immobilized cells was approximately twice that of freely
      suspended cells, and kinetic studies demonstrated that a higher maximum reaction
      rate was achieved with the immobilized cell system. A comparative study using
      both the CDW and pure CP substrates with free cells indicated that the CDW
      contained one or more factors that reduced the bioavailability of CP. The
      immobilized cells retained their activity over a 4-month period of use and
      storage, demonstrating both sustained catalytic activity and long-term mechanical
      stability.

PMID- 12052056
TI  - Effects of increased impeller power in a production-scale Aspergillus oryzae
      fermentation.
AB  - The goal in this study was to determine how increased impeller power affects
      enzyme expression in large-scale (80 m(3)), fed-batch Aspergillus oryzae
      fermentations. An approximate 50% increase in average impeller power was achieved
      by increasing impeller diameter approximately 10%, while operating at slightly
      reduced speed. Measured decreases in terminal (95%) mixing time show increased
      power improved bulk mixing. However, batches operated at increased power had
      lower recombinant enzyme productivity. Biomass assays and image analysis tests
      showed no significant difference between "high power" and control batches,
      suggesting that slower growth, altered morphology, or increased hyphal
      fragmentation were not the cause of reduced productivity. Off-line tests on the
      shear-thinning, highly viscous broth show oxygen limitation occurred after
      transport through the air-liquid interface and imply the limitation may involve
      bulk mixing. Specifically, oxygen transfer may be limited to a small zone
      surrounding each impeller. When this is the case, oxygen mass transfer will be
      determined by both impeller shear and fluid circulation, which have been
      characterized with the energy dissipation/circulation function (EDCF). EDCF
      values during control fermentations were approximately constant at 25 kW m (-3)
      s(-1), while EDCF values during "high power" batches fell linearly from 40 to 15
      kW m (-3) s(-1). The point at which "high power" EDCF values drop below those in
      control fermentations corresponds almost exactly with the point at which product
      titer stops increasing. Thus, our findings suggest oxygen mass transfer was less
      efficient during the latter half of "high power" fermentations because of
      reductions in impeller speed and subsequent decreases in EDCF values. This
      observation has clear implications during the scale-up of viscous fungal
      fermentations, implying that not only is the level of impeller power important,
      but also relevant is how this power is applied.

PMID- 12052057
TI  - Conversion of fumaric acid to L-malic by sol-gel immobilized Saccharomyces
      cerevisiae in a supported liquid membrane bioreactor.
AB  - Conversion of fumaric acid (FA) to L-malic acid (LMA) was carried out in a
      bioreactor divided by two supported liquid membranes (SLMs) into three
      compartments: Feed, Reaction, and Product. The Feed/Reaction SLM, made of tri-n
      octylphosphine oxide (vol 10%) in ethyl acetate, was selective toward the
      substrate, fumaric acid (S(FA/LMA) = 10). The Reaction/Product SLM, made of di(2
      ethylhexyl) phosphate (vol 10%) in dichloromethane, was selective toward the
      product, L-malic acid (S(LMA/FA) = 680). Immobilized yeast engineered to
      overproduce the enzyme fumarase [E.C. 4.2.1.2] was placed in the Reaction
      compartment and served as the catalyst. The yeast was immobilized in small
      glasslike beads of alginate-silicate sol-gel matrix. The construction of the
      bioreactor ensured unidirectional flow of the substrate from the Feed to the
      Reaction and of the product from the Reaction to the Product compartments, with
      the inorganic counterion traveling in the opposite direction. The conversion of
      almost 100%, above the equilibrium value of ca. 84% and higher than that for the
      industrial process, 70%, was achieved. In contrast to the existing industrial
      biocatalytic process resulting in L-malic acid salts, direct production of the
      free acid is described.

PMID- 12052058
TI  - Clavulanic acid degradation in Streptomyces clavuligerus fed-batch cultivations.
AB  - Clavulanic acid (CA) is an important antibiotic that is produced by Streptomyces
      clavuligerus. CA is unstable and product degradation has turned out to have a
      major impact on product titers in fed-batch cultivations. Three different types
      of experiments have been used to elucidate CA degradation under fed-batch
      cultivation conditions. First, the influence of individual medium compounds was
      examined. Second, degradation was monitored during the exponential growth phase
      in batch cultivations. Third, CA degradation was studied in the supernatant of
      samples taken during a fed-batch. In addition, data from six fed-batch
      cultivations were studied to derive information about CA degradation during the
      production phase. These cultivations were based on a mineral medium, containing
      glycerol, glutamate, ammonium, and phosphate as the main nutrients. The ammonium
      concentration had a large influence on the degradation rate constant. In
      addition, either changes in the substrate availability or high concentrations of
      ammonium or glycerol cause a major increase in the degradation rate constant.
      Finally, a linear and a fuzzy logic model were made to predict CA degradation
      rates in these fed-batches.

PMID- 12052059
TI  - Expanded application of a two-phase partitioning bioreactor through strain
      development and new feeding strategies.
AB  - This research demonstrated the microbial treatment of concentrated phenol wastes
      using a two-phase partitioning bioreactor (TPPB). TPPBs are characterized by a
      cell-containing aqueous phase and an immiscible and biocompatible organic phase
      that partitions toxic substrates to the cells on the basis of their metabolic
      demand and the thermodynamic equilibrium of the system. Process limitations
      imposed by the capability of wild-type Pseudomonas putida ATCC 11172 to utilize
      long chain alcohols were addressed by strain modification (transposon
      mutagenesis) to eliminate this undesirable biochemical characteristic, enabling
      use of a range of previously bioavailable organics as delivery solvents.
      Degradation of phenol in a system with the modified strain as catalyst and
      industrial grade Adol 85 NF (primarily oleyl alcohol) as the solvent was
      demonstrated, with the system ultimately degrading 36 g of phenol within 38 h.
      Volumetric phenol consumption rates by wild type P. putida ATCC 11172 and the
      genetically modified derivative revealed equivalent phenol degrading capabilities
      (0.49 g/L x h vs 0.47 g/L x h respectively, in paired fermentations), with the
      latter presenting a more efficient remediation option due to decreased solvent
      losses arising from the modified strain's forced inability to consume the
      delivery solvent as a substrate. Two feeding strategies and system configurations
      were evaluated to expand practical applications of TPPB technology. The ability
      to operate with a lower solvent ratio over extended periods revealed potential
      for long-term application of TPPB to the treatment of large masses of phenol
      while minimizing solvent costs. Repeated recovery of 99% of phenol from
      concentrated phenol solutions and subsequent treatment within a TPPB scheme
      demonstrated applicability of the approach to the remediation of highly
      contaminated "effluents" as well as large masses of bulk phenol. Operation of the
      TPPB system in a dispersed manner, rather than as two distinct phases, resulted
      in volumetric consumption rates similar to those previously achieved only in
      systems operated with enriched air.

PMID- 12052060
TI  - Production of cycloisomaltooligosaccharides from dextran using enzyme immobilized
      in multilayers onto porous membranes.
AB  - Anion-exchange porous hollow-fiber membranes with a thickness of about 1.2 mm and
      a pore size of about 0.30 microm were used as a supporting matrix to immobilize
      cycloisomaltooligosaccharide glucanotransferase (CITase). CITase was immobilized
      to the membrane via anion-exchange adsorption and by subsequent enzymatic cross
      linking with transglutaminase, the amount of which ranged from 3 to 110 mg per
      gram of the membrane. The degree of enzyme multilayer binding was equivalent to
      0.3-9.8. Dextran, as the substrate, was converted into seven- to nine-glucose
      membered cycloisomaltooligosaccharides (CI-7, -8, and -9) at a maximum yield of
      28% in weight at a space velocity of 10 per hour during the permeation of 2.0%
      (w/w) dextran solution across the CITase-immobilized porous hollow-fiber
      membrane. The yield of CIs increased with increasing degree of CITase
      multilayering.

PMID- 12052061
TI  - Critical analysis of lysozyme refolding kinetics.
AB  - The kinetics of lysozyme refolding and aggregation is studied using an existing
      competing first- and third-order reaction scheme. The existing model
      overestimates yield at high refolding concentrations (>1 mg/mL), thus limiting
      its use for reactor design at industrially relevant refolding concentrations.
      This study demonstrates that a pathway exists for the incorporation of refolded
      native protein into aggregates. Specifically, native lysozyme labeled with
      fluorescein isothiocyanate was added to the refolding buffer prior to dilution
      refolding of denatured and reduced lysozyme. Aggregates collected from these
      experiments showed significant fluorescence, indicating that labeled lysozyme had
      been incorporated into the aggregates during refolding. Although the precise
      pathway of incorporation has not been elucidated, it is clear from this work that
      the existing model for lysozyme refolding is not globally applicable. In
      particular, previous work has analytically demonstrated that neglect of a pathway
      from native to aggregate can result in the design of a grossly suboptimal reactor
      strategy. This study demonstrates that such a pathway can exist experimentally
      and emphasizes the need to critically assess refolding kinetic models before
      their use in reactor design equations.

PMID- 12052062
TI  - Evaluation of infection parameters in the production of replication-defective HSV
      1 viral vectors.
AB  - Herpes simplex virus type-1 (HSV-1) is a neurotrophic human pathogen that
      establishes life-long latency in the nervous system. Our laboratory has
      extensively engineered this virus to retain the ability to persist in neurons
      without expression of lytic genes or disease phenotype. Highly defective,
      replication-incompetent HSV mutants are thus potentially ideal for transfer of
      therapeutic transgenes to human nerves where long-term therapy of nervous system
      disease may be provided. A prerequisite for using recombinant HSV vectors for
      therapeutic gene delivery to humans is the development of methods for large-scale
      manufacture of HSV vectors. Here we report studies to identify infection
      parameters that result in high-yield production of immediate early gene deletion
      mutant HSV vectors in complementing cells that supply the deleted essential viral
      functions in trans. Virus yield was correlated with various culture media
      conditions that included pH, glucose metabolism, and serum levels. The results
      demonstrated that systematic media exchange to remove lactate derived from high
      level glucose consumption, maintenance of tissue culture pH at 6.8, and the use
      of 5% fetal bovine serum gave the highest yield of infectious virus. The data
      indicate that these are important parameters to consider for high-yield, large
      scale virus production.

PMID- 12052063
TI  - Penicillin G acylase-fatty lipid biocomposite films show excellent catalytic
      activity and long term stability/reusability.
AB  - The formation of biocomposite films of the pharmaceutically important enzyme
      penicillin G acylase (PGA) and fatty lipids under enzyme-friendly conditions is
      described. The approach involves a simple beaker-based diffusion protocol wherein
      the enzyme diffuses into the lipid film during immersion in the enzyme solution,
      thereby leading to the formation of a biocomposite film. The incorporation of the
      enzyme in both cationic as well as anionic lipids suggests the important role of
      secondary interactions such as hydrophobic and hydrogen bonding in the enzyme
      immobilization process. The kinetics of formation of the enzyme-lipid
      biocomposites has been studied by quartz crystal microgravimentry (QCM)
      measurements. The stability of the enzyme in the lipid matrix was confirmed by
      Fourier transform infrared spectroscopy (FTIR) and biocatalytic activity
      measurements. Whereas the biological activity of the lipid-immobilized enzyme was
      marginally higher than that of the free enzyme, the biocomposite film exhibited
      increased thermal/temporal stability. Particularly exciting was the observation
      that the biocomposite films could be reused in biocatalysis reactions without
      significant loss in activity, which indicates potentially exciting
      biomedical/industrial application of these films.

PMID- 12052064
TI  - Effects of pressing lignocellulosic biomass on sugar yield in two-stage dilute
      acid hydrolysis process.
AB  - Dilute sulfuric acid catalyzed hydrolysis of biomass such as wood chips often
      involves pressing the wood particles in a dewatering step (e.g., after acid
      impregnation) or in compression screw feeders commonly used in continuous
      hydrolysis reactors. This study addresses the effects of pressing biomass
      feedstocks using a hydraulic press on soluble sugar yield obtained from two-stage
      dilute-acid hydrolysis of softwood. The pressed acid-impregnated feedstock gave
      significantly lower soluble sugar yields than the never-pressed (i.e., partially
      air-dried or filtered) feedstock. Pressing acid-impregnated feedstocks before
      pretreatment resulted in a soluble hemicellulosic sugar yield of 76.9% from first
      stage hydrolysis and a soluble glucose yield of 33.7% from second-stage
      hydrolysis. The dilute-acid hydrolysis of partially air-dried feedstocks having
      total solids and acid concentrations similar to those of pressed feedstocks gave
      yields of 87.0% hemicellulosic sugar and 46.9% glucose in the first and second
      stages, respectively. Microscopic examination of wood structures showed that
      pressing acid-impregnated wood chips from 34 to 54% total solids (TS) did not
      cause the wood structure to collapse. However, pressing first-stage pretreated
      wood chips (i.e., feedstock for second-stage hydrolysis) from approximately 30 to
      43% TS caused the porous wood matrix to almost completely collapse. It is
      hypothesized that pressing alters the wood structure and distribution of acid
      within the cell cavities, leading to uneven heat and mass transfer during
      pretreatment using direct steam injection. Consequently, lower hydrolysis yield
      of soluble sugars results. Dewatering of corn stover by pressing did not impact
      negatively on the sugar yield from single-stage dilute-acid pretreatment.

PMID- 12052065
TI  - Swelling induced detachment of chondrocytes using RGD-modified poly(N
      isopropylacrylamide) hydrogel beads.
AB  - Thermally sensitive poly(N-isopropylacrylamide, NIPAAm) hydrogel beads conjugated
      with a cell adhesive motif, GRGDY, were prepared and utilized as cell culture
      substrate for chondrocytes. They were produced to be uniform in size and
      distribution by using calcium alginate as a temporal mold. The RGD moieties were
      introduced, in a spatially selective manner, to the surface of the beads by
      conjugating GRGDY under the precollapsed state at a higher temperature above the
      lower critical solution temperature (LCST). These RGD-conjugated polyNIPAAm beads
      demonstrated a reversible swelling and deswelling behavior around the LCST, which
      enabled the chondrocytes attached on the surface of collapsed beads at 37 degrees
      C to readily detach when the temperature was shifted below 37 degrees C. The cell
      detachment percentage was largely affected by the temperature-dependent
      reswelling extent of the collapsed RGD-modified beads.

PMID- 12052066
TI  - Bioreactor production of human alpha(1)-antitrypsin using metabolically regulated
      plant cell cultures.
AB  - Transgenic rice cell cultures, capable of producing recombinant human alpha(1)
      antitrypsin (rAAT), were scaled up from shake flasks to a 5-L bioreactor. The
      maximum specific growth rates (mu(max)) observed from two bioreactor runs were
      0.40 day(-1) (doubling time of 1.7 days) and 0.47 day(-1) (doubling time of 1.5
      days), and the maximum specific oxygen uptake rates were 0.78 and 0.84 mmol
      O(2)/(g dw h). Using a metabolically regulated rice alpha-amylase (RAmy3D)
      promoter, signal peptide, and terminator, sugar deprivation turned on rAAT
      expression, and rAAT was secreted into the culture medium. After 1 day of culture
      in sugar-free medium, there was still continued biomass growth, oxygen
      consumption, and viability. Extracellular concentrations of 51 and 40 mg active
      rAAT/L were reached 1.7 and 2.5 days, respectively, after induction in a sugar
      free medium. Volumetric productivities for two batch cultures were 7.3 and 4.6 mg
      rAAT/(L day), and specific productivities were 3.2 and 1.6 mg rAAT/(g dw day).
      Several different molecular weight bands of immunoreactive rAAT were observed on
      immunoblots.

PMID- 12052067
TI  - Free sulfhydryl in recombinant monoclonal antibodies.
AB  - Monoclonal antibody (mAb) therapy applications have been growing rapidly in
      recent years. Like other recombinant protein drugs, therapeutic mAb's need to be
      well characterized to ensure their structural and functional integrity. IgG mAb's
      are composed of two heavy and two light chains covalently linked by interchain
      disulfide bonds. Each domain of the heavy or light chain contains one additional
      disulfide bond. Native IgG mAb's, with completely formed disulfide bonds, should
      not bear any free sulfhydryl. This report describes detection and quantification
      of free sulfhydryl in recombinant mAb's produced in Chinese hamster ovary (CHO)
      cells using a fluorescent technique. The method utilizes the fluorescent probe N
      (1-pyrenyl)maleimide (NPM). The purified mAb's appear to be homogeneous under
      native conditions with approximately 0.02 mol of free sulfhydryl per mole of
      protein. Upon denaturation, minor species related to the mAb's are observed on
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the
      free sulfhydryl level is determined to be approximately 0.1 mol/mol of protein.
      These results suggest that a small portion of these recombinant mAb's lack in
      intermolecular disulfide bonds but remain noncovalently associated under native
      conditions. The formation of the free sulfhydryl containing mAb species is likely
      to occur during the culture process and/or protein folding process in the
      endoplasmic reticulum (ER).

PMID- 12052068
TI  - Extractive bioconversion of 2-phenylethanol from L-phenylalanine by Saccharomyces
      cerevisiae.
AB  - The bioconversion of L-phenylalanine (L-Phe) to 2-phenylethanol (PEA) by the
      yeast Saccharomyces cerevisiae is limited by the toxicity of the product. PEA
      extraction by a separate organic phase in the fermenter is the ideal in situ
      product recovery (ISPR) technique to enhance productivity. Oleic acid was chosen
      as organic phase for two-phase fed-batch cultures, although it interfered to some
      extent with yeast viability. There was a synergistic inhibitory impact toward S.
      cerevisiae in the presence of PEA, and therefore a maximal PEA concentration in
      the aqueous phase of only 2.1 g/L was achieved, compared to 3.8 g/L for a normal
      fed-batch culture. However, the overall PEA concentration in the fermenter was
      increased to 12.6 g/L, because the PEA concentration in the oleic phase attained
      a value of 24 g/L. Thus, an average volumetric PEA production rate of 0.26 g L(
      1) h(-1) and a maximal volumetric PEA production rate of 0.47 g L(-1) h(-1) were
      achieved in the two-phase fed-batch culture. As ethanol inhibition had to be
      avoided, the production rates were limited by the intrinsic oxidative capacity of
      S. cerevisiae. In addition, the high viscosity of the two-phase system lowered
      the k(l)a, and therefore also the productivity. Thus, if a specific ISPR
      technique is planned, it consequently has to be remembered that the productivity
      of this bioconversion process is also quickly limited by the k(l)a of the
      fermenter at high cell densities.

PMID- 12052069
TI  - Identification of affinity ligands for protein purification from synthetic
      chemical combinatorial libraries.
AB  - A method to screen combinatorial libraries for the development of selective
      ligands for protein affinity chromatographic purification is described. The
      method is based on the application of parallel combinatorial libraries, and it
      has several potential advantages. The screening procedure is simple and
      straightforward, and it does not require the chemical derivatization of the
      target proteins or even that the target protein be pure. The experiment can also
      be designed to select binders that are less likely to cause protein denaturation.
      Feasibility of this approach is demonstrated with a model study of the
      chromatographic purification of bovine albumin serum (BSA) and Avidin.

PMID- 12052070
TI  - pH Transitions in ion-exchange systems: role in the development of a cation
      exchange process for a recombinant protein.
AB  - Unexpected transient changes in effluent pH can occur during ion-exchange
      chromatography. Such changes can occur even if a column that is equilibrated with
      a buffer receives another solution in the same buffer and of the same pH but of a
      different salt concentration. An attempt is made to understand the basis for this
      phenomenon and apply it to the process purification of a recombinant protein on a
      strong cation-exchange resin. Incomplete column equilibration was eliminated as a
      possible cause of these effects. Various buffering species and various salt ions
      were studied at different solution concentrations to investigate pH transitions
      on strong cation-exchange resins. A further comparison was made between cation
      exchange resins with different backbone chemistries. On the basis of these
      studies, a mechanism is proposed for these phenomena based on competitive
      equilibria between ions from the buffer salts and H(+)/OH(-) ions. In addition to
      the equilibria between these ions and the functional groups on the resins,
      charged groups on the resin backbone were also found to contribute to transient
      pH changes. The results from this study were applied to the cation-exchange step
      for a recombinant protein that was sensitive to pH excursions to help maintain
      activity of the protein during the purification process.

PMID- 12052071
TI  - Factors important in the extraction, stability and in vitro assembly of the
      hepatitis B surface antigen derived from recombinant plant systems.
AB  - The expression of vaccine antigens in edible plant material together with their
      delivery by the oral route constitutes a powerful paradigm, with the potential to
      dramatically reduce the cost of vaccine production and administration, in
      addition to improving distribution and patient compliance. These products will be
      subject to many of the same regulations applied to current injectable vaccines,
      so reliable methods to quantify antigen and ensure stability in crude plant
      extracts are required. As a model system the hepatitis B surface antigen (HBsAg)
      was expressed in soybean and tobacco cell cultures. This complex antigen consists
      of membrane-associated small surface antigen proteins (p24(s)), disulfide cross
      linked to yield dimers and higher multimers. Although the total p24(s) extracted
      from plant cells was relatively unaffected by detergent concentration, the
      quantification of antigenically reactive product depended strongly on the ratio
      of detergent to cell concentration. Furthermore, 1-20% w/v sodium ascorbate
      improved the measured levels of monoclonal-reactive antigen 4- to 12-fold.
      Detergent also influenced antigen stability in cell lysates stored at 4 degrees
      C; under optimum conditions stability was maintained for at least 1 month,
      whereas excess detergent rendered the antigen susceptible to proteolytic
      degradation. This proteolysis could be counteracted by the addition of skim milk
      or its protein component, which stabilized antigenically reactive p24(s) for up
      to 2 months. The immunologically relevant epitopes of HBsAg are critically
      dependent on disulfide bonding. By altering the sodium ascorbate concentration or
      buffer pH the proportion of HBsAg displaying the monoclonal reactive epitopes was
      increased between 8- and 20-fold. In addition, under certain conditions the
      dimerized p24(s) could be converted to oligomeric aggregates, resembling the form
      of the serum-derived antigen. These simple in vitro manipulations, compatible
      with the goal of a minimally processed oral vaccine, may prove valuable in
      increasing the immunogenicity of the plant-derived antigen.

PMID- 12052072
TI  - Protease-containing silicates as active antifouling materials.
AB  - Biocatalytic silicates, composite materials composed of alpha-chymotrypsin and a
      silicate prepolymer, were prepared via a two-step polymerization process
      following solubilization of the enzyme in the polymerization media. This new
      approach resulted in active and stable composites, and a calculated half-life of
      over 350 days in aqueous buffer at 30 degrees C. The high stability and activity
      of this biocatalytic silicate was likely due to the covalent attachment between
      alpha-chymotrypsin and the silicate matrix. The protease-containing silicate was
      resistant to fouling by nonselective protein binding, as demonstrated by the
      dramatically reduced binding of human serum albumin to the silicate material when
      compared to that of a silicate containing pre-inactivated alpha-chymotrypsin.

PMID- 12052073
TI  - Preparative purification of a recombinant protein by hydrophobic interaction
      chromatography: modulation of selectivity by the use of chaotropic additives.
AB  - Development and implementation of a chaotropic wash step following protein
      loading on a hydrophobic interaction chromatographic (HIC) column is described
      for the purification of a recombinant protein. Various agents that reduce protein
      affinity in hydrophobic interaction chromatographic systems were screened for
      their utility in a wash step following protein loading on a Phenyl Fast Flow
      Sepharose HIC column. A combination of sodium thiocyanate, glycerol, and urea was
      selected as a suitable additive for the wash buffer that selectively eluted most
      of the major impurities present in the feed stream. Eluate purity, as monitored
      by reversed-phase chromatography and SDS-PAGE, was significantly increased by
      incorporation of this wash step in the purification process. Incorporation of
      this wash step on HIC enabled a reduction in the overall number of
      chromatographic steps in the downstream purification process for this recombinant
      protein, resulting in improved process yields and significant economic
      advantages. The effect of varying concentrations of each of the three wash
      additives on yield was studied. While the step yield decreased with an increase
      in concentration for urea and sodium thiocyanate, an optimum was observed with
      respect to glycerol concentration. The preferential interaction theory is
      employed to explain this effect.

PMID- 12052074
TI  - High-pressure refolding of disulfide-cross-linked lysozyme aggregates:
      thermodynamics and optimization.
AB  - Previous exploratory work revealed that high pressure (200 MPa), in combination
      with oxido-shuffling agents such as glutathione, effectively refolds covalently
      cross-linked aggregates of lysozyme into catalytically active native molecules,
      at concentrations up to 2 mg/mL (1). To understand further and optimize this
      process, in the current study we varied the redox conditions and levels of
      guanidine hydrochloride (GdnHCl) in the refolding buffer. Maximum refolding
      yields of 80% were seen at 1 M GdnHCl; higher concentrations did not increase
      refolding yields further. A maximum in refolding yield was observed at redox
      conditions with a 1:1 ratio of oxidized to reduced glutathione (GSSG:GSH). Yields
      decreased dramatically at more oxidizing conditions ([GSSG] > [GSH]). Kinetics of
      dissolution and refolding of covalently cross-linked aggregates of lysozyme
      depended strongly on redox conditions. At GSSG:GSH ratios of 4:1, 1:1, and 1:16,
      lysozyme dissolved and refolded with time constants of 62, 20, and 8 h,
      respectively. Estimates of the free energy of unfolding of lysozyme in GdnHCl
      solutions at 200 MPa suggested that the native state of lysozyme is strongly
      favored (ca.18.6 kJ/mol) under the conditions used for dissolution and refolding.

PMID- 12052075
TI  - Modeling and advanced control of recombinant Zymomonas mobilis fed-batch
      fermentation.
AB  - This work presents the development of an unstructured kinetic model incorporating
      the differing degrees of product, substrate, and pH inhibition on the kinetic
      rates of ethanol fermentation by recombinant Zymomonas mobilis CP4:pZB5 for
      growth on two substrates. Product inhibition was observed to start affecting the
      specific growth rate at an ethanol concentration of 20 g/L and the specific
      productivity at about 35-40 g/L. Specific growth rate was also shown to be more
      sensitive to inhibition by lowered pH as well. A model for the inhibition of two
      competing substrates' cellular uptake via membrane transport is proposed.
      Inhibition functions and model parameters were determined by fitting experimental
      data to the model. The model was utilized in a nonlinear model predictive control
      (NMPC) algorithm to control the product concentration during fed-batch
      fermentation to offset the inhibitory effects of product inhibition. Using the
      optimal feeding policy determined online, the volumetric productivity of ethanol
      was improved 16.6% relative to the equivalent batch operation when the final
      ethanol concentration was reached.

PMID- 12052077
TI  - Mechanical deformation of compressible chromatographic columns.
AB  - A one-dimensional model of mechanical deformation of compressible chromatography
      columns is presented. The model is based on linear elasticity and continuum
      mechanics and is compared to a more complete two-dimensional model and one
      dimensional porosity profiles measured by NMR imaging methods. The model provides
      a quantitative description of compression and the effects of wall support during
      scale-up. A simple criterion for the significance of wall support as a function
      of both diameter and length is also developed. Although the model accounts only
      for mechanical deformation, flow compression can be included, and validation
      presented here suggests that a more complete model may be valuable for
      anticipating the effects of scale and aspect ratio on pressure-flow behavior of
      compressible columns.

PMID- 12052076
TI  - Adhesion of Mytilus edulis foot protein 1 on silica: ionic effects on biofouling.
AB  - To determine the effect of the ionic environment on the marine adhesion molecule
      Mytilus edulis foot protein 1 (Mefp-1), atomic force microscopy (AFM) was used to
      measure the adhesion between Mefp-1 and a silica substrate under a range of ionic
      conditions. Both ion strength and type were varied on the basis of the ions
      present in natural seawater. Salts containing monovalent ions (NaCl, KCl)
      increased adhesion only slightly, but salts containing divalent ions (MgCl(2),
      CaCl(2), Na(2)SO(4)) induced multiple jumpouts in the decompression curve similar
      to other biological systems and an increase in hydrodynamic radius as observed by
      light scattering. This behavior may be due to metal complexation between 3,4
      dihydroxyphenyl-L-alanine and o-quinone catechol groups on Mefp-1. The addition
      of a salt containing a trivalent ion (FeCl(3)) resulted in the highest adhesion.
      The strong effect of salt type and concentration suggests that the ionic
      composition of the environment within the mussel byssus may be tailored in order
      to achieve maximum adhesion and minimum curing time.

PMID- 12052078
TI  - Evaluation of process-induced dimensional changes in the membrane structure of
      biological cells using impedance measurement.
AB  - The impact of high intensity electric field pulses, high hydrostatic pressure,
      and freezing-thawing on local structural changes of the membrane was determined
      for potato, sugar beet tissue, and yeast suspensions. On the basis of the
      electrophysical model of cell systems in biological tissues and suspensions, a
      method was derived for determining the extent of local damage of cell membranes.
      The method was characterized by an accurate and rapid on-line determination of
      frequency-dependent electrical conductivity properties from which information on
      microscopic events on cellular level may be deduced. Evaluation was based on the
      measurement of the relative change in the sample's impedance at
      characteristically low (f(l)) and high (f(h)) frequencies within the beta
      dispersion range. For plant and animal cells the characteristic frequencies were
      f(l) approximately 5 kHz and f(h) > 5 MHz and for yeast cells in the range f(l)
      approximately 50 kHz and f(h) > 25 MHz. The observed phenomena were complex. The
      identification of the underlying mechanisms required consideration of the time
      dependent nature of the processing effects and stress reactions of the biological
      systems, which ranged from seconds to several hours. A very low but significantly
      detectable membrane damage (0.004% of the total area) was found after high
      hydrostatic pressure treatment of potato tissue at 200 MPa. The membrane rupture
      in plant tissue cells was higher after freezing and subsequent thawing (0.9% of
      total area for potato cells and 0.05-0.07% for sugar beet cells determined
      immediately after thawing), which increased substantially during the next 2 h.

PMID- 12052079
TI  - Targeting systemically administered proteins to bone by bisphosphonate
      conjugation.
AB  - To develop a methodology for bone-specific delivery of proteins, a bone-seeking
      aminobisphosphonate (aminoBP) was previously conjugated to a model protein,
      bovine serum albumin (BSA). The conjugates were shown to exhibit a high affinity
      to bone in vitro and in vivo. This study was conducted to determine whether the
      systemic delivery of proteins to bone can be increased by aminoBP conjugation.
      Two model proteins used for this study were BSA and lysozyme (LYZ). For each
      protein, an unmodified (i.e., control) and aminoBP-conjugated protein were (125)I
      labeled and injected into rats, and the organ delivery of the proteins were
      determined. Intravenous (IV) injection of aminoBP-BSA resulted in a 2.0- to 3.7
      fold increased delivery to bones as compared to the control protein in young
      rats. In osteopenic, ovariectomized rats, aminoBP conjugation enhanced the bone
      delivery of BSA by 2.2- to 7.5-fold. A 3.7- to 5.6-fold increased delivery was
      also observed for LYZ after IV injection in normal rats. In addition to IV route
      of administration, subcutaneous injection was also effective in delivering a
      higher amount of aminoBP-conjugated proteins to bone. We conclude that
      conjugating bone-seeking aminoBPs to proteins improved their delivery to
      mineralized tissues. The proposed targeting approach has the potential to improve
      the efficacy of recombinant proteins capable of stimulating bone formation by
      enhancing their localization to bones.

PMID- 12052080
TI  - pH-Sensitive hydrogels as gastrointestinal tract absorption enhancers: transport
      mechanisms of salmon calcitonin and other model molecules using the Caco-2 cell
      model.
AB  - The main interest of this work was the investigation of the transport mechanisms
      of salmon calcitonin through the epithelial cell monolayer in the presence and
      absence of pH-sensitive hydrogel nanospheres composed of poly(methacrylic acid
      grafted-poly(ethylene glycol)) (PMAA-g-EG). For this purpose, a gastrointestinal
      cell culture model, the Caco-2 cell line, was employed. The transport of other
      macromolecules such as fluorescein sodium, fluorescein isothiocyanate dextran,
      and (14)C-mannitol were also investigated and compared. Transport experiments
      were conducted in the apical-to-basolateral direction at 37 and 5 degrees C and
      from the basolateral-to-apical direction at 37 degrees C. Results revealed that
      the presence of P(MAA-g-EG) nanospheres increased the transport of paracellularly
      transported molecules such as (14)C-mannitol and fluorescein isothiocyanate
      dextran when compared to controls. Fluorescein sodium salt solutions were
      investigated as an actively transported molecule. The transport of fluorescein
      was affected by the concentration of PEG chains in the structure. Salmon
      calcitonin transport was enhanced in the presence of the nanospheres. The
      comparison of the transport behavior of dextran and calcitonin revealed that the
      main transport mechanism for salmon calcitonin through epithelial cell monolayers
      is predominantly paracellular.

PMID- 12052081
TI  - Production of retrovirus and adenovirus vectors for gene therapy: a comparative
      study using microcarrier and stationary cell culture.
AB  - In gene therapy, retrovirus and adenovirus vectors are extensively used as gene
      delivery vehicles and further large-scale processing of these viral vectors will
      be increasingly important. This study examined stationary and microcarrier cell
      culture systems with respect to the production of a retrovirus vector (encoding a
      monounit hammerhead ribozyme gene with an intron) and an adenovirus vector
      (encoding a reporter lacZ gene). Cytodex 1 and Cytodex 3 solid microcarriers were
      found to be able to provide good cell growth and high-titer vector production in
      suspension cultures. Porous microcarriers such as Cytopore 2 gave slightly lower
      but still efficient growth but produced significantly lower titers of retrovirus
      and adenovirus vector from the producer cells. The specific retrovirus production
      was not proportionally related to the specific growth rate of the producer cells.
      High MOI infection was essential for high-titer production of adenovirus vector
      in 293 cells. Hydrodynamic shear forces on microcarrier-grown cells increased the
      production yield for retrovirus vector but decreased for adenovirus vector. The
      cellular productivity was much more efficient for adenovirus vector produced in
      293 cells as compared to the retrovirus vector produced in PA317-RCM1 cells.
      These findings can provide further insight into the feasibility of applying
      microcarrier cell culture technology to produce gene-therapy virus vectors.

PMID- 12052082
TI  - Chromosome instability in Spodoptera frugiperda Sf-9 cell line.
AB  - Homogeneous cell lines are essential in industry and research if reliable and
      reproducible data are to be obtained. The Spodoptera frugiperda (Sf-9) cell line
      routinely used for the production of recombinant proteins was found to be
      heterogeneous, containing a mixture of diploid and tetraploid cells. Using
      dilution-cloning techniques, diploid and tetraploid subpopulations were isolated
      from a Sf-9 parental cell line, and their cytogenetic state was monitored using
      Vinblastine to arrest cells in mitosis. Flow cytometry was used to obtain a
      snapshot of the predominant subpopulations present to verify the karyological
      results. The rate at which clonal populations digress into the heterogeneous
      state was found to be more rapid for the diploid subpopulation, with the
      emergence of tetraploid cells after only 11 passages, than for the tetraploid
      subpopulation, where diploid clones appeared after 18 passages. The chromosomes
      in both diploid and tetraploid subpopulations as well as the parental cell line
      were found to spontaneously fragment during growth and expansion processes,
      giving rise to variable chromosome numbers. DNA analysis of cell lines obtained
      from laboratories worldwide have shown that the Sf-9 cell line used for the
      production of many recombinant proteins is cytologically unstable, leading to
      varying degrees of polyploidal state depending on its culture history and
      supplier.

PMID- 12052083
TI  - Epoxy sepabeads: a novel epoxy support for stabilization of industrial enzymes
      via very intense multipoint covalent attachment.
AB  - Sepabeads-EP (a new epoxy support) has been utilized to immobilize-stabilize the
      enzyme penicillin G acylase (PGA) via multipoint covalent attachment. These
      supports are very robust and suitable for industrial purposes. Also, the internal
      geometry of the support is composed by cylindrical pores surrounded by the convex
      surfaces (this offers a good geometrical congruence for reaction with the
      enzyme), and it has a very high superficial density of epoxy groups (around 100
      micromol/mL). These features should permit a very intense enzyme-support
      interaction. However, the final stability of the immobilized enzyme is strictly
      dependent on the immobilization protocol. By using conventional immobilization
      protocols (neutral pH values, nonblockage of the support) the stability of the
      immobilized enzyme was quite similar to that achieved using Eupergit C to
      immobilize the PGA. However, when using a more sophisticated three-step
      immobilization/stabilization/blockage procedure, the Sepabeads derivative was
      hundreds-fold more stable than Eupergit C derivatives. The protocol used was as
      follows: (i) the enzyme was first covalently immobilized under very mild
      experimental conditions (e.g., pH 7.0 and 20 degrees C); (ii) the already
      immobilized enzyme was further incubated under more drastic conditions (higher pH
      values, long incubation periods, etc.) in order to "facilitate" the formation of
      new covalent linkages between the immobilized enzyme molecule and the support;
      (iii) the remaining epoxy groups of the support were blocked with very
      hydrophilic compounds to stop any additional interaction between the enzyme and
      the support. This third point was found to be critical for obtaining very stable
      enzymes: derivatives blocked with mercaptoethanol were much less stable than
      derivatives blocked with glycine or other amino acids. This was attributed to the
      better masking of the hydrophobicity of the support by the amino acids (having
      two charges).

PMID- 12052085
TI  - Light-directed simultaneous synthesis of oligopeptides on microarray substrate
      using a photogenerated acid.
AB  - Photogenerated acid (PGA) was used as the acid to remove the protection group
      from amino acids or peptide oligomers. Comparative study of the deprotection
      using a PGA, trisarylsulfonium antimonyhexafluoride (SSb), and trifluoroacetic
      acid (TFA) was performed on glass microscope slides. The results showed that PGA
      can replace TFA in the deprotection step of oligopeptide synthesis with
      comparable efficiencies. Acids needed for the deprotection step were generated in
      situ by light activation of the precursor molecule on the microwell substrate. A
      mask-less laser light illumination system was used to activate the precursor. The
      accuracy of the amino acid sequence of the synthesized oligopeptide and the
      location of the synthesis was illustrated by the specific recognition binding of
      two different models: lead(II) ion-peptide biosensor for lead(II) and human
      protein p53 (residue 20-25)-mouse MAb DO1. After parallel synthesis of the target
      peptide models and their analogues based on the predetermined pattern, specific
      binding treatment, and fluorescence labeling, the fluorescence emission images of
      the oligopeptide microarray showed fluorescence intensity as a result of specific
      binding at the correct locations of the array. The stepwise synthesis
      efficiencies of pentapeptide synthesis on the microwell substrate range are
      approximately 96-100% and do not decrease with respect to the chain length of the
      peptide.

PMID- 12052084
TI  - Characterization of patatin esterase activity in AOT-isooctane reverse micelles.
AB  - Patatin is a family of glycoproteins that accounts for 30-40% of the total
      soluble protein in potato (Solanum tuberosum L.) tubers. This protein has been
      reported not only to serve as a storage protein but also to exhibit lipid acyl
      hydrolase (LAH) activity. In this study patatin is characterized in AOT-isooctane
      reverse micelles. The influence on the enzymatic activity of characteristic
      parameters of reverse micelles, w(o) (= H(2)O/AOT), and the percentage of H(2)O,
      theta, were investigated. The results obtained show that patatin esterase
      activity varies with w(o) but remains constant throughout the range of theta
      values studied. The variation with w(o) showed that the activity follows an S
      shaped behavior pattern, reaching a maximum at about w(o) = 20 for 2% H(2)O.
      Patatin esterase activity was compared with p-nitrophenyl (PNP) fatty acid esters
      of different chain lengths. The activity was much higher for PNP-caprylate. The
      pH optimum was 6.0, different from the value obtained when patatin esterase
      activity was measured in mixed micelle systems. The optimal temperature was 35
      degrees C, above which the activity decreased to almost zero. The kinetic
      parameters were also evaluated (K(m) = 10 mM, V(m) = 158 microM/min, V(m)/K(m) =
      15.8 x 10(-3) min(-1)). This paper shows the suitability of reverse micelles for
      measuring patatin esterase activity, since it allows the study of the enzyme in
      similar conditions to that prevailing in vivo.

PMID- 12052086
TI  - Development of an antibody-based assay for determination of baculovirus titers in
      10 hours.
AB  - The baculovirus expression system has been used to produce large amounts of
      biologically active proteins by infecting insect cells with a recombinant
      baculovirus expressing the target protein. For an efficient expression of the
      target protein, it is necessary to infect insect cells with an adequate amount of
      virus. However, current methods are time-consuming and either have technical
      difficulties or are limited as a result of virus expression mechanism using a
      reporter gene. A novel method is developed to yield virus titers in 10 h that is
      easy to perform using 96-well plates and applicable to both any Autographa
      californica nucleopolyhyderovirus (AcNPV) and Bombyx mori nucleopolyhedrovirus
      (BmNPV)-based recombinant baculovirus. This assay uses an antibody to a DNA
      binding protein to detect the infected cells via immunostaining. The titer is
      determined by counting foci produced as a result of infection of the virus under
      a fluorescent microscope. The required incubation period was shortened
      considerably because infected cells expressed viral antigens at the post
      infection time of 4 h. Therefore, 10 h was enough to estimate the virus titer
      including virus infection time, insect cell culture, and estimation of virus
      titer. Titers determined using this immunological assay are comparable, both in
      value and validity, to those obtained using a traditional method, provided that
      the stocks have titers above 10(3) pfu/mL.

PMID- 12052088
TI  - Use of dye affinity chromatography for the purification of Aerococcus viridans
      lactate oxidase.
AB  - Lactate oxidase was purified from Aerococcus viridans (A. viridans) by dye
      affinity chromatography and FPLC ion exchange chromatography. The lactate oxidase
      could be purified by comparatively simple procedures, the purification achieved
      from a crude extract of A. viridans was 41-fold with a specific activity of 143
      units/(mg of protein). The purified enzyme was a L-lactate oxidase, which
      catalyses the conversion of L-lactate in the presence of molecular oxygen to
      pyruvate and H(2)O(2). This purified lactate oxidase showed an apparent molecular
      mass of 48,200 in SDS-PAGE and the native molecular weight, as estimated by FPLC
      gel filtration, was 187,300. This molecular weight indicates that lactate oxidase
      exists in tetrameric form after gel filtration. To differing degrees, all the
      triazine dyes tested were inhibitors of lactate oxidase, solutions of free
      triazine dyes showing an inhibition mechanism which was both time- and pH
      dependent.

PMID- 12052087
TI  - Expression of double Vitreoscilla hemoglobin enhances growth and alters ribosome
      and tRNA levels in Escherichia coli.
AB  - In several organisms, expression of a gene encoding dimeric hemoglobin (VHb) from
      the obligate aerobic bacterium Vitreoscilla stercoraria has been shown to
      increase microaerobic cell growth and enhance oxygen-dependent cell metabolism.
      In an attempt to further improve these effects of VHb, a gene encoding two vhb
      genes connected by a short linker of six base pairs was constructed and expressed
      in Escherichia coli(double VHb). Escherichia coli cells expressing double VHb
      reached a cell density 19% higher than that of cells expressing native VHb. The
      protein production per cell remained constant since the increase in cell growth
      was accompanied by an increase in protein content by 16%. Investigation of
      ribosome and tRNA content revealed that cells expressing double VHb reached their
      maximal capacity of protein synthesis later during cultivation than cells
      expressing native VHb, and furthermore they reached considerably higher levels of
      ribosome and tRNA compared to that of the VHb-expressing cells.

PMID- 12052090
TI  - Cooperative effect of artificial chaperones and guanidinium chloride on lysozyme
      renaturation at high concentrations.
AB  - It has been recognized that the artificial chaperone system,
      cetyltrimethylammonium bromide and beta-cyclodextrin, is effective for enhancing
      protein renaturation. In this work, we studied the effect of the artificial
      chaperone system and guanidinium chloride (GdmCl) on the oxidative renaturation
      of lysozyme at 0.21-1.05 mg/mL, and a kinetic model based on the competition
      between protein folding and aggregation was employed to express the renaturation
      process. The refolding rate constant increased, while the aggregation rate
      constant decreased, with increasing concentration of the artificial chaperones.
      With increasing GdmCl concentration (0.28-2 M), both rate constants decreased,
      but there existed a specific GdmCl concentration that maximized the ratio of the
      two rate constants and thus the renaturation yield. The results obviously
      indicated the cooperative effect of GdmCl and the artificial chaperones on
      enhancing protein renaturation.

PMID- 12052089
TI  - Olive oil mill waste waters decoloration and detoxification in a bioreactor by
      the white rot fungus Phanerochaete flavido-alba.
AB  - Olive oil mill wastewater (OMW) is produced as waste in olive oil extraction.
      With the purpose of treating this highly polluting waste, a number of experiments
      were conducted in a laboratory-scale bioreactor with the white rot fungus
      Phanerochaete flavido-alba (P. flavido-alba). It is known that this fungus is
      capable of decolorizing OMW in static or semistatic cultures at Erlenmeyer scale
      and at 30 degrees C. The objective of this work was to prove that P. flavido-alba
      could decolorize OMW in submerged cultures and that it is capable of reducing OMW
      toxicity at room temperature (25 degrees C) and in a laboratory-scale bioreactor.
      In the experiments conducted, manganese peroxidase (MnP) and laccase enzymes were
      detected; however, unlike other studies, lignin peroxidase was not found to be
      present. Decoloration obtained after treatment was 70%. The reduction of aromatic
      compounds obtained was 51%, and the toxicity of the culture medium was reduced by
      up to 70%. We can therefore state that P. flavido-alba is capable of reducing
      important environmental parameters of industrial effluents and that prospects are
      positive for the use of this process at a larger scale, even when working at room
      temperature.

PMID- 12052091
TI  - Control and fault diagnosis in bottom fermentation systems using parity space
      approach.
AB  - The main objective of this note is to describe a real-time fault diagnosis and
      control for a cylindroconical fermenter to laboratory scale as an alternative to
      the classic systems. Development of a good controller for a fed-batch reactor is
      not enough without a fault diagnosis system. We are working to expand this idea.
      The failure detection system is based on the parity space approach joined with a
      fuzzy controller with more robustness and of superior performance in MIMO systems
      compared to conventional strategies. A 2-week period is reported.

PMID- 12052092
TI  - Effect of pH on high-temperature production of bacterial penicillin acylase in
      Escherichia coli.
AB  - High-temperature-oriented production of bacterial penicillin acylase (PAC), which
      is usually expressed at low temperatures (less than 30 degrees C), was
      demonstrated in this study via heterologous expression of the Providencia
      rettgeri (P. rettgeri) pac gene in Escherichia coli (E. coli). While it is
      possible to produce PAC at a temperature as high as 37 degrees C, the
      environmental condition (specifically, culture pH) critically affected culture
      performance. Production of PAC at 37 degrees C was feasible only when culture pH
      was close to neutral (i.e., 6.5-7.5). Outside this pH range, cell physiology for
      the host/vector system was seriously affected, resulting in poor culture
      performance. In acidic culture environments, temperature significantly affected
      the pac expression level and specific PAC activity decreased with an increase in
      culture temperature. In basic culture environments, cell growth was seriously
      inhibited though the pac expression level was minimally affected by temperature.
      Such unusual types of pH and temperature effects on pac expression were never
      reported for bacterial PACs. The results suggest that culture pH should be
      precisely controlled for the current host/vector systems being applied on the
      overproduction of P. rettgeri PAC in E. coli at high temperatures.

PMID- 12052093
TI  - Effect of lacY expression on homogeneity of induction from the P(tac) and P(trc)
      promoters by natural and synthetic inducers.
AB  - The role of the Escherichia coli lactose permease (LacY) in the homogeneous
      induction of the lactose-inducible promoters P(tac) and P(trc) by the natural
      inducer lactose and the synthetic inducer isopropyl-beta-D-thiogalactopyranoside
      (IPTG) was investigated. Lactose requires active transport by LacY, whereas IPTG
      can freely penetrate the cell wall. In E. coli strains lacking a functional LacY,
      IPTG is required for induction of P(tac) and P(trc). In E. coli strains carrying
      a functional LacY, induction of P(trc) and P(tac) with intermediate
      concentrations of lactose gave rise to two subpopulations, one fully induced and
      one uninduced, whereas a single, fully induced population resulted when high
      inducer concentrations were used. In contrast, induction with IPTG gave rise to a
      single population of cells at all inducer concentrations in both lacY and lacY(+)
      strains.

PMID- 12052094
TI  - Optimization of high molecular weight pullulan production by Aureobasidium
      pullulans in batch fermentations.
AB  - Of five strains of Aureobasidium pullulans studied, NRRL Y-2311-1 yielded the
      highest titer (26.2 g/L) of pullulan and formed the lowest amount of melanin-like
      pigment. Sucrose was superior to glucose as the carbon and energy source on the
      basis of yield and titer of pullulan produced. Pullulan titer was higher (26.2 vs
      5.1 g/L), biomass concentration was lower (6.9 vs 12.7 g/L), and DO was lower (0
      vs 60% of saturation) when the fermenter was agitated by a marine propeller
      compared to Rushton impellers. Pullulan produced by strain NRRL Y-2311-1 ranged
      in weight-average molar mass (M(w)) from 486 KDa and number-average molar mass
      (M(n)) from 220 Da on day 1 of growth to 390 KDa and 690 Da on day 6; M(w)
      declined by about 35% from day 1 to day 3, the day of maximum pullulan titer. For
      the other strains, the ranges of molar mass on the day of maximum pullulan titer
      were 338-614 KDa (M(w)) and 100-6820 Da (M(n)).

PMID- 12052095
TI  - Sickle cell anaemia: epidemiology and cost of illness.
AB  - The purpose of this paper was to review the research examining the epidemiology
      of and costs associated with sickle cell anaemia (SCA). Although there is general
      acceptance that Black populations are at greatest risk of the disease, estimates
      of disease incidence and prevalence vary greatly among different Black
      populations. In addition, the sickle cell haemoglobinopathy poses a health
      problem to many other ethnic groups, including populations native to Italy,
      Greece, Turkey, Saudi Arabia, India, Pakistan, Bangladesh, China, and Cyprus. As
      penicillin prophylaxis has been shown to reduce the risk of sepsis among children
      with SCA, many governments have established newborn screening programmes to
      improve the health outcomes for patients with this disease. As a group, patients
      with SCA incur large numbers of hospital admissions, emergency department visits,
      and outpatient visits, often at substantial costs, hence, obtaining adequate
      health insurance is a problem for many patients. A common theme present in
      studies reviewed in this article is that a small proportion of patients tends to
      account for a majority of the total healthcare costs. As new diagnostic methods
      and treatment options become available, balancing costs associated with SCA and
      quality of healthcare will continue to present challenges to many healthcare
      providers and insurers.

PMID- 12052097
TI  - A fair innings for NICE?

PMID- 12052098
TI  - Estimating the effect of changes in body mass index on health state preferences.
AB  - OBJECTIVE: To investigate the effect of changes in body mass index (BMI) on
      health state preferences (HSP). DESIGN: Multiple regression analysis on pooled
      data from a clinical study, predicting final HSP as a function of changes in BMI
      and initial HSP, controlling for age and gender. Subgroup analyses according to
      clinically relevant subgroups were performed. SETTING: Primary care practice
      sites. PATIENTS: 402 obese patients of varying disease severity. MAIN OUTCOME
      MEASURES: BMI was operationalised as (weight in kilograms)/ (height in
      metres)(2). HSP were measured directly as visual analogue scale (VAS) scores, and
      converted to time trade-off (TTO) scores. RESULTS: A one unit decrease in BMI
      over a 1-year period was associated with a 0.017 gain in utility units (utils).
      This estimate is comparable to utility gains observed for other widely used
      treatments (e.g. revascularisation for intermittent claudication, renal
      transplantation). It varies little over the observed range of VAS to TTO
      conversion values, and is a conservative estimate compared with using the
      unconverted VAS scores. If attempts to use weight reduction treatment in only the
      patients who successfully meet strict weight reduction targets are successful,
      the gain in HSP experienced by such patients may exceed this estimate. Patients
      with BMI values >or=28 with hyperglycaemia appear to have the greatest gain in
      HSP for a given change in BMI over 1 year. CONCLUSIONS: The effect of weight
      reduction on HSP can be significant, at least in the short term. Estimates of HSP
      changes presented herein may be useful in economic evaluations of weight
      reduction treatments.

PMID- 12052099
TI  - Reporting heterogeneity in the measurement of health and health-related quality
      of life.
AB  - OBJECTIVE: To investigate heterogeneity (systematic and observable variation) in
      health or health-related quality-of-life reports across population groups, for a
      given level of 'true health'. DESIGN: The investigators undertook full sit-down
      face-to-face interviews with 1999 individuals representing Jewish Israelis aged
      45 to 75 years who resided in urban Israeli communities in 1993. Three popular
      measures of health and health-related quality of life were used: a categorical
      subjective evaluation, the 36-item Short Form health survey and a visual analogue
      health-related quality-of-life rating scale. The empirical analysis of the
      various relationships was based on the use of multiple-indicator linear
      structural equation models with latent variables. The model was estimated by the
      2-stage least squares (2SLS) method. RESULTS: In general, the results confirm the
      existence of substantial measure-specific heterogeneity in reporting (with
      differences associated with age, gender and education level) for all three
      measures. CONCLUSIONS: The existence of heterogeneity in reporting renders the
      results of quality-of-life investigations sensitive to the sample used, and
      considerably limits the ability to generalise from these results and make
      comparisons with other populations. Economic evaluations based on self-reports
      are thus sensitive not only to the measure used, but also to the sample used. The
      application of results to populations differing in their socioeconomic and
      demographic structures, even if similar in the distribution of 'true health',
      might be misleading.

PMID- 12052096
TI  - Cost effectiveness of treatments for amyotrophic lateral sclerosis: a review of
      the literature.
AB  - Amyotrophic lateral sclerosis (ALS) is a difficult to diagnose, fatal,
      progressive degenerative disease with an average survival time of 2 to 5 years.
      Percutaneous endoscopic gastrotomy (PEG) and bi-level intermittent positive
      pressure (BIPAP) ventilation may be the major interventions leading to longer
      survival of patients with ALS. Riluzole has been shown to have modest effects on
      survival (as opposed to functional) gains and is currently the only drug approved
      for the treatment of ALS. There is conflicting evidence with regard to the
      ability of recombinant human insulin-like growth factor (rhIGF-I) to retard ALS
      progression. Mechanical ventilation (via a tracheostomy tube) is expensive, but
      is widely used in later stage patients with ALS in the US. A review of nine cost
      effectiveness studies of riluzole and one of rhIGF-I found the following: drug
      costs and survival gains are the major drivers of cost effectiveness; survival
      gains are estimated from truncated databases with a high degree of uncertainty;
      more accurate stage-specific utility weights based on patients who agreed to
      treatment are needed; case incidence-based evaluations should be carried out;
      cost-effectiveness ratios are insensitive to discount rates; employment and
      caregiver issues or externalities have been widely ignored; threshold acceptance
      cost-effectiveness values are ill-defined and evaluations are not generalisable
      to other countries because of cost and treatment style differences. On account of
      the high degree of uncertainty pertaining to survival gains and the relatively
      high costs per life years or quality-adjusted life-years gained, and while
      acknowledging that not every therapy has to be cost effective (e.g. orphan
      drugs), it is still inconclusive as to whether or not riluzole or rhIGF-1 can be
      considered as cost-effective therapies for ALS.

PMID- 12052101
TI  - A piece of my mind. Everything.

PMID- 12052100
TI  - Use of healthcare services by patients treated with risperidone versus
      conventional antipsychotic agents.
AB  - OBJECTIVE: To determine whether the use of risperidone in a US managed-care
      environment is associated with a reduction in the use of mental healthcare
      services. METHODS: Mental health service use and costs for patients with
      psychoses treated with risperidone versus those treated with conventional
      antipsychotic agents were compared by both between-group and within-group
      comparisons. The study controlled for differences between the groups. Only direct
      medical costs were considered. All costs were for the years 1994 to 1996.
      PERSPECTIVE: US managed care plan. RESULTS: Costs (excluding antipsychotic drug
      costs) per member per month (PMPM) were 180 US dollars lower with risperidone (p
      < 0.05); per member per year (PMPY) costs were 2160 US dollars lower. In patients
      who received both risperidone and conventional treatments, PMPM costs were 212 US
      dollars (2544 US dollars PMPY) lower during risperidone treatment. Total costs
      (including antipsychotic drug costs) were 624 US dollars PMPY lower with
      risperidone by between-group comparisons and 1008 US dollars PMPY lower by within
      group comparisons. CONCLUSIONS: These results show that higher risperidone
      acquisition costs are offset by reductions in other mental healthcare costs,
      particularly inpatient hospitalisation costs. This indicates that risperidone may
      be a more economical choice than traditional antipsychotics for the treatment of
      psychoses.

PMID- 12052105
TI  - Evolving treatment strategies for epilepsy.

PMID- 12052106
TI  - Genomics and proteomics may help clinicians individualize cancer treatment.

PMID- 12052107
TI  - Business learns wisdom of treating employees with psychiatric disability.

PMID- 12052108
TI  - New bioethics council offers no recommendations.

PMID- 12052109
TI  - From the Food and Drug Administration.

PMID- 12052110
TI  - From the Centers for Disease Control and Prevention. Nonoxynol-9 spermicide
      contraception use--United States, 1999.

PMID- 12052111
TI  - From the Centers for Disease Control and Prevention. Fixed obstructive lung
      disease in workers at a microwave popcorn factory--Missouri, 2000-2002.

PMID- 12052116
TI  - Racial disparities in health care.

PMID- 12052117
TI  - Racial disparities in health care.

PMID- 12052118
TI  - Racial disparities in health care.

PMID- 12052120
TI  - Factors in tuberculosis contact investigations.

PMID- 12052122
TI  - Factors in tuberculosis contact investigations.

PMID- 12052123
TI  - Fast food franchises in hospitals.

PMID- 12052124
TI  - Patient complaints and malpractice risk.
AB  - CONTEXT: A small number of physicians experience a disproportionate share of
      malpractice claims and expenses. If malpractice risk is related in large measure
      to factors such as patient dissatisfaction with interpersonal behaviors, care and
      treatment, and access, it might be possible to monitor physicians' risk of being
      sued. OBJECTIVE: To examine the association between physicians' patient complaint
      records and their risk management experiences. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective longitudinal cohort study of 645 general and specialist physicians
      in a large US medical group between January 1992 and March 1998, accounting for
      2546 physician-years of care. MAIN OUTCOME MEASURES: Computerized records of all
      unsolicited patient complaints were recorded by the medical center's patient
      affairs office, coded to characterize the nature of the problem and alleged
      offender, and compared with each physician's risk management records for the same
      period. RESULTS: Both patient complaints and risk management events were higher
      for surgeons than nonsurgeons. Specifically, 137 (32%) of the 426 nonsurgeons had
      at least 1 risk management file compared with nearly two thirds (137 [63%] of
      219) of all surgeons (chi2(1)= 54.7, P<.001). Both complaint and risk management
      data were positively correlated with physicians' volume of clinical activity.
      Logistic regression revealed that risk management file openings, file openings
      with expenditures, and lawsuits were significantly related to total numbers of
      patient complaints, even when data were adjusted for clinical activity.
      Predictive concordance of specialty group, complaint count, clinical activity,
      and sex for risk management file openings was 84%; file openings with
      expenditures, 83%; lawsuits, 81%; and multiple lawsuits, 87%. CONCLUSIONS:
      Unsolicited patient complaints captured and recorded by a medical group are
      positively associated with physicians' risk management experiences.

PMID- 12052125
TI  - Respiratory infections with Pseudomonas aeruginosa in children with cystic
      fibrosis: early detection by serology and assessment of risk factors.
AB  - CONTEXT: Patients with cystic fibrosis (CF) are susceptible to lower respiratory
      tract infections with Pseudomonas aeruginosa and typically acquire this organism
      in early childhood. Once P aeruginosa infection is established, eradication may
      be impossible, and progressive lung disease often aggravates morbidity and
      mortality risks. The ability to diagnose CF by genetic testing at birth makes it
      possible to determine the temporal sequence of events that result in P aeruginosa
      associated pulmonary infections. OBJECTIVE: To evaluate the longitudinal
      relationship between the production of an antibody response against P aeruginosa
      and clinical factors associated with P aeruginosa pulmonary infections in
      patients with CF diagnosed in early life. DESIGN, SETTING, AND PATIENTS: Serum
      samples and oropharyngeal cultures (protocol cultures) were obtained at 6-month
      intervals from April 15, 1985, to April 15, 2000 (or for up to 180 months
      depending on their enrollment date) from 68 patients at 2 centers in Madison and
      Milwaukee, Wis, diagnosed through the Wisconsin CF Neonatal Screening Project, a
      longitudinal cohort study. Additional cultures were obtained at examining
      physicians' discretion (all cultures). MAIN OUTCOME MEASURES: Time to serum IgG,
      IgA, and IgM antibody titer of at least 1:256 against P aeruginosa, assessed by
      enzyme-linked immunosorbent assay using cell lysate, exotoxin A, and elastase as
      antigens; time to organism isolation from respiratory samples; time to Wisconsin
      Cystic Fibrosis Radiograph (WCXR) score of 5 or more. RESULTS: The median time to
      an antibody titer of at least 1:256 was 17.8, 24.2, and 70.9 months for cell
      lysate, exotoxin A, and elastase, respectively. The rise of anti-cell lysate and
      anti-exotoxin A titers to 1:256 or more occurred a mean of 11.9 (P<.001) and 5.6
      (P =.04) months, respectively, before the isolation of P aeruginosa for all
      cultures and 18.2 (P<.001) and 11.9 (P =.006) months, respectively, before
      protocol cultures. There was no significant difference between the rise of anti
      cell lysate and anti-exotoxin A titer and a WCXR score of 5 or more (P =.24
      and.32, respectively). Treatment with long-term, non-Pseudomonas oral antibiotics
      and integration of CF infants with older, chronically infected patients were
      associated with a significantly increased risk of P aeruginosa pulmonary
      infection. CONCLUSIONS: In CF patients diagnosed through neonatal screening, P
      aeruginosa pulmonary infections occurred 6 to 12 months before the organism was
      isolated from respiratory secretions. The longitudinal monitoring of P aeruginosa
      antibody titers, in concert with WCXR score, should facilitate diagnosis and
      treatment of P aeruginosa pulmonary infections in young children with CF.

PMID- 12052126
TI  - Rupture rate of large abdominal aortic aneurysms in patients refusing or unfit
      for elective repair.
AB  - CONTEXT: Among patients with abdominal aortic aneurysm (AAA) who have high
      operative risk, repair is usually deferred until the AAA reaches a diameter at
      which rupture risk is thought to outweigh operative risk, but few data exist on
      rupture risk of large AAA. OBJECTIVE: To determine the incidence of rupture in
      patients with large AAA. DESIGN AND SETTING: Prospective cohort study in 47
      Veterans Affairs medical centers. PATIENTS: Veterans (n = 198) with AAA of at
      least 5.5 cm for whom elective AAA repair was not planned because of medical
      contraindication or patient refusal. Patients were enrolled between April 1995
      and April 2000 and followed up through July 2000 (mean, 1.52 years). MAIN OUTCOME
      MEASURE: Incidence of AAA rupture by strata of initial and attained diameter.
      RESULTS: Outcome ascertainment was complete for all patients. There were 112
      deaths (57%) and the autopsy rate was 46%. Forty-five patients had probable AAA
      rupture. The 1-year incidence of probable rupture by initial AAA diameter was
      9.4% for AAA of 5.5 to 5.9 cm, 10.2% for AAA of 6.0 to 6.9 cm (19.1% for the
      subgroup of 6.5-6.9 cm), and 32.5% for AAA of 7.0 cm or more. Much of the
      increased risk of rupture associated with initial AAA diameters of 6.5-7.9 cm was
      related to the likelihood that the AAA diameter would reach 8.0 cm during follow
      up, after which 25.7% ruptured within 6 months. CONCLUSION: The rupture rate is
      substantial in high-operative-risk patients with AAA of at least 5.5 cm in
      diameter and increases with larger diameter.

PMID- 12052127
TI  - Correlation of quality measures with estimates of treatment effect in meta
      analyses of randomized controlled trials.
AB  - CONTEXT: Specific features of trial quality may be associated with exaggeration
      or shrinking of the observed treatment effect in randomized studies. Therefore,
      assessment of trial quality is often used in meta-analysis. However, the degree
      to which specific quality measures are associated with treatment effects has not
      been well established across a broad range of clinical areas. OBJECTIVE: To
      determine if quality measures are associated with treatment effect size in
      randomized controlled trials (RCTs). DESIGN: Quality measures from published
      quality assessment scales were evaluated in RCTs included in meta-analyses from 4
      medical areas (cardiovascular disease, infectious disease, pediatrics, and
      surgery). Included meta-analyses incorporated at least 6 RCTs, examined
      dichotomous outcomes, and demonstrated significant between-study heterogeneity in
      the odds ratio (OR) scale. MAIN OUTCOME MEASURES: Relative ORs comparing overall
      treatment effect (summary OR) of high vs low-quality studies, as determined by
      each quality measure, with relative ORs less than 1 indicating larger treatment
      effect in low-quality studies. RESULTS: Twenty-four quality measures were
      analyzed for 276 RCTs from 26 meta-analyses. Relative ORs of high vs low-quality
      studies for these quality measures ranged from 0.83 to 1.26; none was
      statistically significantly associated with treatment effect. The proportion of
      studies fulfilling specific quality measures varied widely in the 4 medical
      areas. In analyses limited to specific medical areas, placebo control,
      multicenter studies, study country, caregiver blinding, and statistical methods
      were significantly associated with treatment effect on 7 occasions. These
      relative ORs ranged from 0.40 to 1.74. However, the directions of these
      associations were not consistent. CONCLUSIONS: Individual quality measures are
      not reliably associated with the strength of treatment effect across studies and
      medical areas. Although use of specific quality measures may be appropriate in
      specific well-defined areas in which there is pertinent evidence, findings of
      associations with treatment effect cannot be generalized to all clinical areas or
      meta-analyses.

PMID- 12052128
TI  - Using tobacco-industry marketing research to design more effective tobacco
      control campaigns.
AB  - To improve tobacco-control efforts by applying tobacco-industry marketing
      research and strategies to clinical and public health smoking interventions, we
      analyzed previously secret tobacco-industry marketing documents. In contrast to
      public health, the tobacco industry divides markets and defines targets according
      to consumer attitudes, aspirations, activities, and lifestyles. Tobacco marketing
      targets smokers of all ages; young adults are particularly important. During the
      1980s, cost affected increasing numbers of young and older smokers. During the
      1990s, eroding social acceptability of smoking emerged as a major threat, largely
      from increasing awareness of the dangers of secondhand smoke among nonsmokers and
      smokers. Physicians and public health professionals should use tobacco-industry
      psychographic approaches to design more relevant tobacco-control interventions.
      Efforts to counter tobacco marketing campaigns should include people of all ages,
      particularly young adults, rather than concentrating on teens and young children.
      Many young smokers are cost sensitive. Tobacco-control messages emphasizing the
      dangers of secondhand smoke to smokers and nonsmokers undermine the social
      acceptability of smoking.

PMID- 12052129
TI  - Tobacco advertising in the United States: a proposal for a constitutionally
      acceptable form of regulation.
AB  - Lorillard Tobacco Co. v Reilly is the latest in a series of Supreme Court cases
      striking down public health regulation of advertising as a violation of the First
      Amendment. In its decision, the Supreme Court significantly reduced the scope of
      constitutionally acceptable forms of regulation of tobacco advertising and
      created an almost insoluble dilemma for public health authorities. Control over
      advertising, along with taxes and restrictions on smoking in public settings,
      plays an important role in the public health response to tobacco. Those committed
      to reducing the patterns of cigarette-related morbidity and mortality should
      broaden their advertising-related strategies and consider the role that greater
      disclosure of the health harms of tobacco can have on reducing consumption.
      Toward this end, we propose a comprehensive system of taxation and regulation
      designed to increase public appreciation and comprehension of the health risks of
      cigarettes. First, we consider a tax to be levied on tobacco advertising and
      promotion or, as an alternative, a new excise tax, the proceeds of which would be
      used exclusively to fund a Centers for Disease Control and Prevention-directed
      national antitobacco campaign. Second, all print advertising should be required
      to carry public health warnings equivalent to 50% of the space devoted to the
      advertisement. Third, manufacturers should be required to devote one full side of
      cigarette packages to graphic pictorials displaying the dangers of smoking. The
      tobacco industry would no doubt respond by declaring such efforts an unwarranted
      burden, an example of constitutionally suspect compelled speech. However, this
      would be a battle worth engaging, because it might have an impact on tobacco
      related morbidity and mortality in the United States.

PMID- 12052130
TI  - Temporal arteritis: a cough, toothache, and tongue infarction.
AB  - Temporal arteritis, the most common form of systemic vasculitis in adults, is a
      panarteritis that chiefly involves the extracranial branches of the carotid
      artery. The condition is illustrated in this article by the case of a 79-year-old
      woman with a dry cough, toothache, tongue infarction, and vision loss. The mean
      age of onset is 72 years and the disease rarely occurs in persons younger than 50
      years. The most common presenting manifestations are headache, jaw claudication,
      polymyalgia rheumatica, and visual symptoms. Eighty-nine percent of patients have
      an erythrocyte sedimentation rate greater than 50 mm/h. However, about 40% of
      patients present with atypical manifestations, including fever of unknown origin,
      respiratory tract symptoms (especially dry cough), and large artery involvement.
      Familiarity with such unusual manifestations of temporal arteritis facilitates
      early diagnosis and treatment, thereby reducing the risk of vision loss.

PMID- 12052131
TI  - Counteracting cigarette advertising.

PMID- 12052132
TI  - Putting the patient in patient safety: linking patient complaints and malpractice
      risk.

PMID- 12052137
TI  - Fast forwarding pharmacogenomics.

PMID- 12052138
TI  - Microarray technologies -- an overview. The University of California San Diego
      Extension, Bioscience, Microarray Technologies -- an overview, March 13-15, 2002.

PMID- 12052140
TI  - The role of genomics in the discovery of novel targets for antibiotic therapy.
AB  - The emergence of antibiotic resistance and multi-drug resistance in bacterial
      pathogens underscores the need for the development of novel classes of
      antibiotics. The availability of complete genome sequence data from many
      important human pathogens provides a wealth of fundamental information. This
      allows us to define each gene and thus to better understand molecular
      pathogenesis. New techniques have enabled the identification and characterization
      of genes that are critical for bacterial growth and survival during infection.
      The combination of genome sequence data and new technologies make it possible to
      systematically explore the function of each open reading frame in a genome and
      identify any potential molecular targets for drug discovery. With particular
      emphasis on antibacterial therapy, this review discusses genome-based
      technologies and their important applications to anti-infective drug discovery.

PMID- 12052139
TI  - Pharmacogenetics and folate metabolism -- a promising direction.
AB  - Folate metabolism is the target of two major drug groups: folate antagonists
      (e.g., methotrexate) and thymidylate synthase inhibitors (for example, 5
      fluorouracil). These agents are widely used in cancer chemotherapy, as treatment
      for rheumatoid arthritis, and for other conditions. The administration of these
      drugs in cancer chemotherapy can induce a state of acute folate depletion with
      sometimes life-threatening toxic sequelae. Recent studies suggest that
      polymorphisms in folate-metabolizing enzymes may modify the therapeutic
      effectiveness and toxicity of drugs targeting folate metabolism. This review
      briefly summarizes major drugs targeting the folate pathway and describes common
      polymorphisms in folate-metabolizing enzymes and transport proteins.
      Pharmacogenetic studies investigating the relevance of these polymorphisms with
      respect to patients' response to antifolate chemotherapeutic agents are
      discussed. Investigating genetic variability in folate metabolism in the
      framework of pharmacogenetics is a promising field. Findings to date illustrate
      the potential for targeting therapy based on patients' genotypes with improved
      outcomes and reduced toxicity.

PMID- 12052141
TI  - Human flavin-containing monooxygenase (form 3): polymorphisms and variations in
      chemical metabolism.
AB  - The human flavin-containing monooxygenases catalyze the oxygenation of
      nucleophilic heteroatom-containing drugs, xenobiotics and endogenous materials.
      Evidence for six forms of the FMO gene exist but it is FMO form 3 (FMO3) that is
      the prominent form in adult human liver that is likely to be associated with the
      bulk of FMO-mediated metabolism. An understanding of the substrate specificity of
      human FMO3 is beginning to emerge and several examples of drugs and chemicals
      extensively metabolized by FMO3 have been reported. Expression of FMO3 is species
      and tissue-specific, but unlike human cytochrome P450 (CYP450), mammalian FMO3
      does not appear to be inducible. Interindividual variation in FMO3-dependent
      metabolism of drugs, chemicals and endogenous materials is therefore more likely
      to be due to genetic and not environmental effects. Certain mutations of the
      human FMO3 gene have been associated with abnormal N-oxygenation of
      trimethylamine. Deficient N-oxygenation of trimethylamine results in a condition
      called trimethylaminuria. Some treatment strategies for this inborn error of
      metabolism are discussed. Other common variants of the FMO3 gene including E158K,
      V257M and E308G have been observed. It is possible that allelic variation of
      human FMO3 causes abnormal metabolism of chemicals and has clinical implications
      for human drug metabolism, but this is an understudied area. Human FMO3 allelic
      variation may eventually be shown to contribute to interindividual and
      interethnic variability in FMO3-mediated metabolism. Human FMO3 may be another
      example of an environmental gene that participates in a protective mechanism to
      help shield humans from potentially toxic exposure to chemicals. Heterogeneity in
      the relative frequencies of single and multiple site alleles, haplotypes and
      genotypes of the human FMO3 amongst various ethnic groups suggests population
      differences.

PMID- 12052142
TI  - Pharmacogenomic considerations of the paraoxonase polymorphisms.
AB  - The high density lipoprotein (HDL)-associated enzyme paraoxonase-1 (PON1)
      exhibits a substrate-dependent activity polymorphism as well as a large
      variability in plasma levels among individuals. The PON1 activity polymorphism is
      determined mainly by a glutamine(Q)/arginine(R) substitution at position 192 of
      PON1 (PON1(Q192R)). There is one additional polymorphism in the coding region at
      L55M, five in the 5 cent regulatory region and four in the 3' untranslated
      region. One of the five promoter polymorphisms (C-108T) appears to have a major
      effect on the levels of PON1 found in plasma. Two factors are important to
      consider in evaluating the pharmacogenetics of PON1 in an individual, the amino
      acid present at position 192 and the level of their plasma PON1. 'PON1 status',
      measured easily via a two-substrate assay, provides data for both of these
      critical factors. As such, PON1 status will be more useful than genotyping alone
      for identifying individuals at risk for cardiovascular disease, for predicting
      sensitivity to OP insecticides, and possibly nerve agents, for predicting the
      disposition of drugs known to be activated or hydrolyzed by PON1 and for
      developing robust pharmacokinetic models for each of these roles of these roles
      of PON1.

PMID- 12052144
TI  - Genes and their polymorphisms in mono- and multifactorial cardiomyopathies:
      towards pharmacogenomics in heart failure.
AB  - Cardiomyopathies are diseases of the myocardium associated with cardiac
      dysfunction, and are classified as dilated cardiomyopathy (DCM), hypertropic
      cardiomyopathy (HCM) and restrictive cardiomyopathy. Heart failure and sudden
      death are the two major complications. Also, since DCM is the primary indication
      for heart transplantation and HCM the primary cause of sudden death in young
      athletes, the socioeconomic impact of these diseases is important. Recently, the
      role of the genetic background in both monogenic and multifactorial
      cardiomyopathies has been studied, which has led to a better understanding of the
      underlying mechanisms that promote the development and progression of these
      diseases. Preliminary data suggest interactions between pharmacological treatment
      and genetic polymorphisms, which appear to be the first steps towards the
      application of pharmacogenetics in heart failure.

PMID- 12052143
TI  - Arylamine N-acetyltransferases and drug response.
AB  - Arylamine N-acetyltransferases (NATs) play an important role in the interaction
      of competing metabolic pathways determining the fate of and response to
      xenobiotics as therapeutic drugs, occupational chemicals and carcinogenic
      substances. Individual susceptibility for drug response and possible adverse drug
      reactions are modulated by the genetic predisposition (manifested for example, by
      polymorphisms) and the phenotype of these enzymes. For all drugs metabolized by
      NATs, the impact of different in vivo enzyme activities is reviewed with regard
      to therapeutic use, prevention of side effects and possible indications for risk
      assessment by phenotyping and/or genotyping. As genes of NATs are susceptibility
      genes for multifactorial adverse effects and xenobiotic-related diseases, risk
      prediction can only be made possible by taking the complexity of events into
      consideration.

PMID- 12052145
TI  - How many SNPs does a genome-wide haplotype map require?
AB  - We derive and compare several estimates of the number of SNPs that would be
      required to form the basis of a complete haplotype survey of the human genome.
      Our estimates make use of reports published by Stephens et al. [1], Patil et al.
      [2] and Daly et al. [3]. The estimated number of SNPs required for a genome-wide
      haplotype survey ranges from 180K (based on a European sample of 16 chromosomes)
      to 600K (based on an ethnically diverse sample of 164 chromosomes). We discuss
      the implications of using cohorts of different size and ethnic composition and
      the usefulness of public SNP databases for this effort. Finally, we estimate the
      experimental effort and cost required to complete a genome-wide haplotype survey.

PMID- 12052146
TI  - SNPs on human chromosomes 21 and 22 -- analysis in terms of protein features and
      pseudogenes.
AB  - SNPs are useful for genome-wide mapping and the study of disease genes. Previous
      studies have focused on SNPs in specific genes or SNPs pooled from a variety of
      different sources. Here, a systematic approach to the analysis of SNPs in
      relation to various features on a genome-wide scale, with emphasis on protein
      features and pseudogenes, is presented. We have performed a comprehensive
      analysis of 39,408 SNPs on human chromosomes 21 and 22 from the SNP consortium
      (TSC) database, where SNPs are obtained by random sequencing using consistent and
      uniform methods. Our study indicates that the occurrence of SNPs is lowest in
      exons and higher in repeats, introns and pseudogenes. Moreover, in comparing
      genes and pseudogenes, we find that the SNP density is higher in pseudogenes and
      the ratio of nonsynonymous to synonymous changes is also much higher. These
      observations may be explained by the increased rate of SNP accumulation in
      pseudogenes, which presumably are not under selective pressure. We have also
      performed secondary structure prediction on all coding regions and found that
      there is no preferential distribution of SNPs in a -helices, b -sheets or coils.
      This could imply that protein structures, in general, can tolerate a wide degree
      of substitutions. Tables relating to our results are available from
      http://genecensus.org/pseudogene.

PMID- 12052147
TI  - Analyzing array data using supervised methods.
AB  - Pharmacogenomics is the application of genomic technologies to drug discovery and
      development, as well as for the elucidation of the mechanisms of drug action on
      cells and organisms. DNA microarrays measure genome-wide gene expression patterns
      and are an important tool for pharmacogenomic applications, such as the
      identification of molecular targets for drugs, toxicological studies and
      molecular diagnostics. Genome-wide investigations generate vast amounts of data
      and there is a need for computational methods to manage and analyze this
      information. Recently, several supervised methods, in which other information is
      utilized together with gene expression data, have been used to characterize genes
      and samples. The choice of analysis methods will influence the results and their
      interpretation, therefore it is important to be familiar with each method, its
      scope and limitations. Here, methods with special reference to applications for
      pharmacogenomics are reviewed.

PMID- 12052148
TI  - Psychiatric Genomics, inc.
AB  - Mental illness affects millions of patients and has been shown to have multiple
      genetic components. The interaction of environmental factors, such as stress,
      with the expression of genetic susceptibilities has hampered the development of
      novel and effective drug treatments. A new approach is described that can
      discover novel classes of drugs for the treatment of the underlying causes of
      these diseases rather than their symptoms. This approach screens drug candidates
      according to their ability to alter the expression of multiple genes in a
      multiparameter high-throughput screening assay (MPHTS SM) that does not require a
      prori knowledge of the targets of screening assays. Clinical development of drug
      candidates will be pursued through partnerships with pharmaceutical companies
      and/or large biotechnology companies.

PMID- 12052165
TI  - Thrombin receptor antagonists; recent advances in PAR-1 antagonist development.
AB  - The receptor for the serine protease thrombin, the protease-activated receptor-1
      (PAR-1), has been recently characterized. Its key roles in thrombin-stimulated
      human platelet activation, vascular endothelial and smooth muscle proliferation,
      inflammatory responses and neurodegeneration suggest receptor involvement in
      various disorders such as arterial thrombosis, atherosclerosis, restenosis,
      inflammation and myocardial infarction. It has been established that thrombin
      elicits the majority of its effects via PAR-1. PAR-1 has a novel mechanism of
      activation. The receptor, a member of the seven-transmembrane domain receptor
      family, is cleaved by thrombin at a specific site on the N-terminal extension,
      and a newly exposed N-terminus acts as a  tethered ligand  to activate the
      receptor itself. The need for development of a PAR-1 antagonist that may be
      valuable as a therapeutic agent has been recognized. An intriguing challenge is
      the necessity of the antagonist to compete with an intramolecular ligand while
      showing no intrinsic activity. The lead compounds were found to be synthetic
      peptides containing N-terminal hexapeptide or pentapeptide (Ser-Phe-Leu-Leu-Arg
      Asn, Ser-Phe-Leu-Leu-Arg) or modified sequences (TRAPs; thrombin receptor
      activating peptides), which exhibit full PAR-1 agonist activity. Selective PAR-1
      antagonists have already been synthesized. Though their potency is still not
      enough to justify therapeutic use, it is clear that future progress will bring a
      novel class of drugs-thrombin receptor antagonists. The emphasis of this review,
      therefore, will be placed on advances in the discovery of potent and selective
      PAR-1 antagonists.

PMID- 12052166
TI  - The application of microwave irradiation as new convenient synthetic procedure in
      drug discovery.
AB  - Heterocyclic compounds hold a special place among pharmaceutically important
      natural and synthetic materials. The remarkable ability of heterocyclic nuclei to
      serve both as biomimetics and reactive pharmacophores has largely contributed to
      their unique value as traditional key elements of numerous drugs. In both lead
      identification and lead optimization processes there is an acute need for new
      organic small molecules. Traditional methods of organic synthesis are orders of
      magnitude too slow to satisfy the demand for these compounds. The fields of
      combinatorial and automated medicinal chemistry have been developed to meet the
      increasing requirement of new compounds for drug discovery, within these fields,
      speed is of the essence. The efficiency of microwave flash-heating chemistry in
      dramatically reducing reaction times (reduced from days and hours to minutes and
      seconds) has recently been proven in several different fields of organic
      chemistry. We believe that the time saved by using focused microwaves is
      potentially important in traditional organic synthesis but could be of even
      greater importance in high-speed combinatorial and medicinal chemistry. In this
      review, it is impossible to cover all significant developments in the area of
      microwave-assisted organic synthesis (MAOS). Rather, outlines the basic
      principles behind the technology and summarizes the areas in which microwave
      technology has made an impact, to date. Specific attention is given to
      application of microwave irradiation in liquid systems, and in the solid state as
      well of several representative biologically interesting nuclei. In addition we
      report some of the most recently disclosed applications in combinatorial
      chemistry.

PMID- 12052167
TI  - Pharmacological strategies to increase the antitumor activity of methylating
      agents.
AB  - Among methylating agents of clinical interest, temozolomide is a novel antitumor
      compound that has raised particular interest due to its acceptable safety profile
      and activity against tumors poorly responsive to conventional chemotherapy, such
      as malignant glioma and metastatic melanoma. Moreover, the drug has recently
      shown promising antitumor activity in a patient affected by primary brain
      lymphoma and is currently under phase II clinical trials for leptomeningeal
      metastases from leukemia and lymphoma or for brain metastases from lung and
      breast cancers. The antitumor activity of TMZ, that generates different types of
      methyl adducts (70% N7-methylguanine, 10% N3-methyladenine and 9% O6
      methylguanine), has been mainly attributed to the formation of O6-methylguanine
      adducts. Indeed, tumor cell susceptibility to TMZ is strongly affected by the
      functional status of DNA repair systems, involved either in the removal of methyl
      adducts from O6G or in the apoptotic signaling triggered by O6-methylG:T
      mispairs. This review will focus on the different pharmacological strategies
      aimed at overcoming tumor resistance to TMZ such as new formulations of the drug
      or dosing schedules, and combined treatments with other chemotherapeutic agents,
      modulators of DNA repair systems, or gene therapy. The potential use of N3
      methyladenine selective agents in the case of tumors tolerant to O6-methylguanine
      will be also discussed.

PMID- 12052168
TI  - Arylpiperazines with affinity toward alpha(1)-adrenergic receptors.
AB  - In the last years, alpha(1) adrenoceptors (alpha(1)-AR) have been the subject of
      intense research, in part because receptor-binding studies and molecular biology
      have opened up new aspects of understanding but also because of the potential to
      find new drugs possibly acting toward pathophysiological processes where alpha(1)
      AR are involved, such as benign prostatic hyperplasia (BPH) or hypertension. At
      present, arylpiperazines represent one of the most studied classes of molecules
      with affinity at alpha(1)-AR. In fact, a large amount of work has been done and
      reported, describing synthetic procedures, biological evaluation at both alpha(1)
      AR and the corresponding subtypes, and structure-activity relationships (SARs).
      In this paper, a review based on a literature survey aimed at focusing on the
      structural properties that a compound should possess to show affinity toward
      alpha(1)-AR is presented. Moreover, the identification and optimization of the
      structural features of a hit compound derived from a pharmacophore-based database
      search, leading to a new class of arylpiperazinylalkyl pyridazinone derivatives
      with alpha(1)-AR affinity is reported.

PMID- 12052169
TI  - Resistance to beta-lactam antibiotics: structure and mechanism based design of
      beta-lactamase inhibitors.
AB  - Resistance to antibiotics is currently a major health concern in treating
      infectious diseases. The most common mechanism of resistance to beta-lactam
      antibiotics is the production of beta-lactamases, which destroy beta-lactam
      antibiotics before they reach the bacterial target. Combination therapy, which
      involves treatment with a beta-lactam antibiotic and a beta-lactamase inhibitor,
      has been successfully used to control resistance during last two decades. Due to
      the lack of effectiveness of the currently available beta-lactamase inhibitors
      against class C enzymes and new variants of beta-lactamases, there is a need to
      develop an inhibitor with broad-spectrum activity. Since the discovery of
      clavulanic acid, there has been an enormous research effort in this area to
      identify better antibiotic/inhibitor combinations and to understand the molecular
      bases for interactions between beta-lactam antibiotics, beta-lactamases, and beta
      lactamase inhibitors. This review describes some of the structure- and mechanism
      based approaches to design of new beta-lactamase inhibitors and the study of
      probable mechanisms of inhibition using X-ray, electrospray ionization mass
      spectrometry, and molecular modeling techniques.

PMID- 12052170
TI  - Targeting cysteine residues of biomolecules: new approaches for the design of
      antiviral and anticancer drugs.
AB  - Modification of cysteine (Cys) residues in proteins, due to (i) the participation
      of the thiol moiety of this amino acid in oxido-reductions reactions; (ii) its
      ability to strongly coordinate transition metal ions; or (iii) its nucleophilic
      nature and facile reaction with electrophiles, may be of critical importance for
      the design of novel types of pharmacological agents. Application of such
      procedures, recently led to the design of novel antivirals, mainly based on the
      reaction of zinc finger proteins with disulfides and related derivatives. This
      approach was particularly successful for developing novel anti-HIV and anti-HPV
      agents. Several new anticancer therapeutic approaches, mainly targeting tubulin,
      Ras and fanesyl transferase among others, have also been reported. Miscellaneous
      other agents/procedures which found less applications for the moment, and which
      are based on Cys modification reactions, are reviewed. This unique amino acid
      offers very interesting possibilities to develop particularly useful
      pharmacological agents, which generally possess a completely different mechanism
      of action as compared to classical agents in clinical use, avoiding their major
      problems such as multidrug-resistance of antivirals or antitumor agents or high
      toxicity associated with classical such chemotherapeutic agents.

PMID- 12052171
TI  - Serotonin N-acetyltransferase: mechanism and inhibition.
AB  - Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT)
      catalyzes the rate-limiting step in the biosynthesis of the circadian hormone
      melatonin from serotonin. Although melatonin was identified 40 years ago,
      relatively little is known about its (patho)physiological roles, and a solid
      scientific foundation is still lacking for most therapeutic applications
      currently claimed for melatonin. The development of potent, specific, and cell
      permeable inhibitors for AANAT should constitute an important strategy to address
      these issues. These inhibitors are also potential therapeutics for various
      sleep/mood disorders. This review will focus on the efforts toward developing in
      vitro and in vivo AANAT inhibitors, including basic mechanistic studies on AANAT,
      which have played an important role in design.

PMID- 12052172
TI  - Bisphosphonate prodrugs.
AB  - Bisphosphonates (BP) are pyrophosphate analogs having a P-C-P backbone. The oral
      bioavailability of BPs is ca. 1%, due to high ionisation at physiological pH.
      Using the prodrug approach, oral absorption can be increased by masking one or
      more ionizable groups (clodronate, etidronate), or using a targeting carrier
      system (alendronate, pamitronate).

PMID- 12052173
TI  - Cancer chemotherapy and heterocyclic compounds.
AB  - The search for pharmacological approaches to neoplastic disease has made some
      impressive gains started after 1940 when the antileukemic activity of nitrogen
      mustard was discovered during world war II. It is generally accepted that
      neoplastic transformation is related to genes alteration or oncogene activation,
      so the progress in the development of the new drugs for treatment of malignant
      diseases has been rapid, both in revealing pathobiology of the diseases and
      discovery of new drugs. In addition attempts have been made to define optimal
      combinations, treatment strategies and patient support measures. Cancer
      chemotherapy is now of established value and a highly specialized field. Among
      the modifications to the family of antitumor compounds, heterocyclic organic
      compounds have been extensively applied by many groups in order to modify the
      reactivity profile. Pyrrole, pyrimidine, indole, quinoline and purine are few
      classes of heterocycles which showed interesting cytotoxicity profiles. The
      updated material related to these modifications has been rationalized and
      ordered, in order to offer an overview of the argument.

PMID- 12052174
TI  - The search for gamma-secretase and development of inhibitors.
AB  - A considerable body of evidence has accumulated in recent years implicating the
      beta-amyloid protein (Abeta) in the etiology of Alzheimer s disease (AD). The
      highly hydrophobic Abeta can nucleate and form neurotoxic fibrils that are the
      principal components of the cerebral plaques characteristic of AD. Abeta is
      formed from the amyloid-beta precursor protein (APP) through two protease
      activities. First, beta-secretase cleaves APP at the Abeta N-terminus, resulting
      in a soluble, secreted APP derivative (beta-APPs) and a 12 kDa membrane-retained
      C-terminal fragment. The latter is further processed to Abeta by gamma
      secretases, which cleave within the single transmembrane region. Other APP
      molecules can be cleaved by alpha-secretase within the Abeta region, thus
      precluding Abeta formation. Both beta- and gamma- secretase have become prime
      targets for the development of therapeutic agent that reduce Abeta production.
      Beta-secretase has recently been identified as a new membrane-anchored aspartyl
      protease in the cathepsin D family. Inhibitor profiling, site-directed
      mutagenesis, and affinity labeling together have suggested that the multi-pass
      presenilins are gamma-secretases, novel intramembrane-cleaving aspartyl proteases
      activated through autoproteolysis. In this article, we review the current
      knowledge of gamma-secretase biochemistry and cell biology and the development of
      inhibitors of this important therapeutic target.

PMID- 12052175
TI  - The search for alpha-secretase and its potential as a therapeutic approach to
      Alzheimer s disease.
AB  - In the nonamyloidogenic processing pathway the Alzheimer s amyloid precursor
      protein (APP) is proteolytically cleaved by alpha-secretase. As this cleavage
      occurs at the Lys16-Leu17 bond within the amyloid beta domain, it prevents
      deposition of intact amyloidogenic peptide. In addition, the large ectodomain
      (sAPP(alpha)) released by the action of alpha-secretase has several
      neuroprotective properties. Studies with a range of hydroxamic acid-based
      compounds, such as batimastat, indicate that alpha-secretase is a zinc
      metalloproteinase, and members of the adamalysin family of proteins, TACE, ADAM10
      and ADAM9, all fulfil some of the criteria required of alpha-secretase. APP is
      constitutively cleaved by alpha-secretase in most cell lines. However, on
      stimulation with muscarinic agonists or activators of protein kinase C, such as
      phorbol esters, the alpha-secretase cleavage of APP is up-regulated. The
      constitutive alpha-secretase activity is primarily at the cell surface, while the
      regulated activity is predominantly located within the Golgi. The beneficial
      action of cholinesterase inhibitors may in part be due to activation of
      muscarinic receptors, resulting in an up-regulation of alpha-secretase. Other
      agents can also increase the nonamyloidogenic cleavage of APP including estrogen,
      testosterone, various neurotransmitters and growth factors. As the alpha
      secretase cleavage of APP both precludes the deposition of the amyloid beta
      peptide and releases the neuroprotective sAPP(alpha), pharmacological up
      regulation of alpha-secretase may provide alternative therapeutic approaches for
      Alzheimer s disease.

PMID- 12052176
TI  - The challenge of inhibiting Abeta polymerization.
AB  - The discovery of small molecules that inhibit beta-peptide and other amyloid
      fibril formation has been impeded by featureless structure-activity
      relationships, low apparent efficacy of inhibition, and by the perception that
      protein-protein interactions are too diffuse to be proper medicinal chemistry
      targets. Atomic resolution structural information on the critical target species
      are lacking. Despite these difficulties, substoichiometric inhibitors of
      fibrillogenesis have been reported. By carefully defining assay systems and
      considering a spectrum of data from different types of measurements, medicinal
      chemistry can improve molecular structures and their measured effectiveness can
      be better understood. Compounds with good pharmacokinetic and toxicologic
      profiles that persist in the target tissue at useful concentrations may be as
      useful as would extremely high affinity inhibitors with less favorable biological
      properties.

PMID- 12052177
TI  - Beta-secretase as a therapeutic target for inhibitor drugs.
AB  - Recent identification of beta-scretasse being a membrane-associated aspartic
      protease has stimulated strong interest on this enzyme as a therapeutic target
      for Alzheimer s disease. Here we review the current understanding in the
      structure-function relationship as well as the status in the design of its
      inhibitors of this protease, memapsin 2 (BACE, ASP-2). The development in the
      basic tools, such as the preparation of recombinant memapsin 2, the assay method
      for kinetic measurements of inhibition, the determination of the subsite
      specificity and the crystal structure of memapsin 2 complexed to a tight-binding
      inhibitor, has made the structural based inhibitor design possible. More recent
      inhibitors, having Ki values in the nanomolar range and molecular size in low 700
      Da, show some promise that clinically useful inhibitors of beta-scretasse may be
      attainable.

PMID- 12052178
TI  - Selecting nucleic acids for biosensor applications.
AB  - In vitro selection can be used to generate nucleic acid binding species
      (aptamers) and catalysts (ribozymes) that can recognize a variety of molecules.
      Because nucleic acid function is largely derived from readily tabulated secondary
      structures, it has proven possible to engineer aptamers and ribozymes to function
      as biosensors. Labeling nucleic acids with reporter molecules has yielded simple
      antibody substitutes, but by relying on ligand-dependent conformational changes
      it has also proven possible to generate biosensors that can recognize and
      specifically report the presence of ligands in homogenous solution. It may prove
      possible to generate signaling aptamers and allosteric ribozymes (aptazymes) that
      are responsive to a large fraction of an organismal proteome or metabolome using
      automated methods. Nucleic acid biosensor arrays for non-nucleic acid targets
      could likely be generated with the same facility as DNA chips.

PMID- 12052179
TI  - Exploring ligand-DNA space using type IIS restriction enzymes.
AB  - Investigating ligand-DNA interactions using type IIS restriction enzymes (IISRE)
      as footprinting reagents is reviewed and contemplated. Ligand binding at a
      IISRE's cleavage but not sequence recognition site protects DNA from strand
      scission. This spatial arrangement has been exploited in the development of
      qualitative (combinatorial) and quantitative ligand-DNA investigative methods
      collectively termed Type IIS Restriction Enzyme Footprinting (cIISREF and qIISREF
      respectively). In cIISREF, the consensus binding sequence of a ligand is sought
      by using a IISRE to segregate combinatorial library members that are bound by
      ligand from those that are not. A PCR is performed following the segregation step
      to enrich the library in ligand binding (i.e. uncut) sequences. It might be
      possible that diversities approaching 10(30) unique sequences could be
      simultaneously searched using this homogeneous and biologically relevant method.
      For qIISREF, a ligand-DNA equilibrium constant is measured by quantifying the
      amounts of target and control DNA IISRE cleavage products as a function of ligand
      concentration. The control sequence is engineered to not bind ligand. Along with
      illustrating these methods by reviewing published works, current concerns and
      future prospects for IISREF are discussed.

PMID- 12052180
TI  - Automated acquisition of aptamer sequences.
AB  - While the in vitro selection of nucleic acid binding species (aptamers) requires
      numerous liquid-handling steps, these steps are relatively straightforward and
      the overall process is therefore amenable to automation. Here we demonstrate that
      automated selection techniques are capable of generating aptamers against a
      number of diverse protein targets. Automated selection techniques can be
      integrated with automated analytical methods, including sequencing, determination
      of binding constants, and structural analysis. The methods that have so far been
      developed can be further multiplexed, and it should soon be possible to attempt
      the selection of aptamers against organismal proteomes or metabolomes.

PMID- 12052181
TI  - Rationally designed allosteric variants of hammerhead ribozymes responsive to the
      HIV-1 Tat protein.
AB  - Hammerhead ribozymes that are subject to allosteric control by small molecule and
      oligonucleotide effectors have been reported recently. Rational design has been
      an effective strategy for the creation of these ribozymes, which incorporate
      structurally interdependent hammerhead motifs and effector-binding sequences. In
      this paper we report the rational design of the first protein-responsive
      allosteric ribozymes that are regulated by the HIV-1 Tat. The TAR-Tat interaction
      of HIV-1 has the interesting feature that both Tat and arginine are able to bind
      to and bring about comparable conformational changes in the TAR loop. Here we
      describe the construction of two classes of TAR-modified hammerhead ribozymes and
      their response to Tat protein and to its derivatives. Instances of both
      allosteric activation and inhibition were found. Interestingly, the activation
      response was stimulated by both Tat and argininamide while the inhibitory
      response was stimulated by Tat and by its derivative peptide, ADP1, but not by
      argininamide. Overall, the extent of allosteric response in our ribozymes was
      modest relative to those reported for ribozymes with small molecule effectors.
      Future work utilizing combinatorial approaches along with elements of rational
      design should reveal the means by which highly efficient, protein-mediated
      allostery of ribozymes may be achieved.

PMID- 12052182
TI  - Driving in vitro selection of anti-HIV-1 TAR aptamers by magnesium concentration
      and temperature.
AB  - In vitro selection with either DNA or RNA libraries was performed against the TAR
      RNA element of HIV-1. The role of the selection conditions on the outcome of the
      selection was evaluated by varying the magnesium concentration and the
      temperature. The selection stringency was demonstrated to determine i) the
      affinity of the best identified aptamers for the TAR target, and ii) the type of
      interaction between the two partners. Selections performed with a DNA library
      under low (4 degrees C, 10 mM magnesium) and high stringency (23 degrees C, 3 mM
      magnesium) led to the emergence of "kissing aptamers"; but even if the motif
      interacting directly with the TAR loop were identical in the two kinds of
      aptamers, the consensus was extended from eight to thirteen nucleotides when the
      Mg(2+) concentration was decreased from 10 to 3 mM. Similar kissing aptamers were
      selected at 23 degrees C and 37 degrees C starting with two different RNA
      libraries under identical ionic conditions. In addition, selection performed at
      37 degrees C yielded a significant proportion of antisense sequences. Only
      antisense RNAs complementary to the TAR loop competitively inhibited the
      association of a Tat peptide with TAR.

PMID- 12052183
TI  - Improving metal ion specificity during in vitro selection of catalytic DNA.
AB  - Metal ions play important roles in both the structure and function of catalytic
      DNA and RNA. While most natural catalytic RNA molecules (ribozymes) are active in
      solutions containing Mg(2+), in vitro selection makes it possible to search for
      new catalytic DNA/RNA that are specific for other metal ions. However, previous
      studies have indicated that the in vitro selection protocols often resulted in
      catalytic DNA/RNA that were equally active or sometimes even more active with
      metal ions other than the metal ion of choice. To improve the metal ion
      specificity during the in vitro selection process, we implemented a negative
      selection strategy where the nucleic acid pool was subjected to a solution
      containing competing metal ions. As a result, those nucleic acids that were
      active with those metal ions are discarded. To demonstrate the effectiveness of
      the negative selection strategy, we carried out two parallel in vitro selections
      of Co(2+)-dependent catalytic DNA. When no negative selection was used in the
      selection process, the resulting catalytic DNA molecules were more active in
      solutions of Zn(2+) and Pb(2+) than in Co(2+). On the other hand, when the
      negative selection steps were inserted between the normal positive selection
      steps, the resulting catalytic DNA molecules were much more active with Co(2+)
      than in other metal ions including Zn(2+) and Pb(2+). These results suggest
      strongly that in vitro selection can be used to obtain highly active and specific
      transition metal ion-dependent catalytic DNA/RNA, which hold great promise as
      versatile and efficient endonucleases as well as sensitive and selective metal
      ion sensors.

PMID- 12052184
TI  - Nodulisporic acid: its chemistry and biology.
AB  - The discovery of the natural product nodulisporic acid A (NsA A) and its potent,
      systemic insecticidal activity at Merck Research Laboratories in 1992 stimulated
      intense scientific scrutiny. Interest in this new class of indole diterpenes led
      to extensive delineation of its properties, both chemical and biological.
      Synthetic modification of NsA A served to identify its pharmacologically
      permissive and non-permissive regions, produced semisynthetic derivatives with
      enhanced adulticidal flea efficacy (both in vitro and in vivo), and provided
      useful tools to support biological studies. Early observations in rodent models
      showed a wide therapeutic index for NsA A and detailed mechanism of action
      investigations demonstrated that it selectively modulated an invertebrate
      specific glutamate-gated ion channel for which no mammalian homolog exists.
      Consistent with these mechanistic conclusions, dogs treated orally with either
      NsA A or closely related amide analogs (15 mg/kg dosages) showed no apparent
      toxicity, and measurement of systemic flea efficacy in these animals demonstrated
      that prolonged antiparasitic activity was attained, up to 14 days subsequent to
      treatment with a single p.o. dose for fleas or up to 4 weeks for ticks. The
      extended flea efficacy was correlated to both the in vivo pharmacokinetic profile
      of a given analog and its intrinsic in vitro potency against fleas. In addition,
      studies directed towards the total synthesis of NsA A have been reported.

PMID- 12052185
TI  - Evaluation and development of spinosyns to control ectoparasites on cattle and
      sheep.
AB  - The spinosyns are a novel family of fermentation-derived natural products that
      exhibit potent insecticidal activities. Spinosad, a naturally-occurring mixture
      of spinosyn A and spinosyn D, has successfully established its utility for crop
      protective applications in the agrochemical field. Potential applications of this
      unique chemical family of macrolides also have been investigated in the field of
      animal health. Applications for the control of blowfly strike and lice on sheep
      have now been commercially developed and registered in Australia and potential
      applications for the control of ectoparasites on cattle are being studied.

PMID- 12052186
TI  - Therapy and prevention of parasitic insects in veterinary medicine using
      imidacloprid.
AB  - Ectoparasitic insects play a major role in veterinary medicine. The flea,
      especially the cat flea (Ctenocephalides felis felis Bouch  1835) is the most
      important ectoparasite worldwide. The cat flea parasitizes not only on dogs and
      cats but also on other warm-blooded animals including humans. The veterinary
      importance of flea infestation are dermatological conditions due to allergic
      reactions to antigens in the flea saliva and the transmission of infectious
      agents like bacteria, viruses and helminths. Insecticides used in veterinary
      medicine today have to fulfil criteria of elimination of a existing flea
      infestation (therapy) and prevention (prophylaxis) of new infestation for weeks.
      Imidacloprid is a compound of the chemical class of CNI (chloronicotinyl
      insecticides syn. neonicotinoids) that fits these criteria. The high selectivity
      towards the site of action within insects together with the high safety margin on
      mammals allowed to develop imidacloprid as an insecticide for agricultural use
      and finally for the application as a veterinary medicine. The major features of
      imidacloprid chemistry, toxicology and the development and use as a veterinary
      medicinal remedy are described.

PMID- 12052187
TI  - Cephalosporins in veterinary medicine - ceftiofur use in food animals.
AB  - Cephalosporins are an important class of antibacterial agents in use today for
      both humans and animals. Four generations of cephalosporins have evolved, all of
      which contain the beta-lactam sub-structure first found in penicillin. The range
      of cephalosporins available for use in food-producing animals, which is the
      subject of this review, is limited compared to humans. A few first- and second
      generation cephalosporins are approved worldwide strictly for treatment of
      mastitis infections in dairy cattle. A third-generation cephalosporin, ceftiofur,
      and a fourth-generation cephalosporin, cefquinome, have been developed strictly
      for veterinary use. Cefquinome has been approved in several countries for the
      treatment of respiratory disease in cattle and swine, foot rot in cattle and for
      mastitis in dairy cattle. Ceftiofur has worldwide approvals for respiratory
      disease in swine, ruminants (cattle, sheep and goats) and horses and has also
      been approved for foot rot and metritis infections in cattle. Ceftiofur has also
      been approved in various countries for early mortality infections in day-old
      chicks and turkey poults. This review summarizes cephalosporin use in general
      terms, and provides an overview of ceftiofur, in terms of its spectrum of
      activity, indications, metabolism, and degradation in the environment. The safety
      of ceftiofur is also reviewed, with respect to food-animal residues, rapid
      metabolism and degradation, and non-persistence of ceftiofur in the environment.
      The environmental fragility of cephalosporins have not been explored generally,
      but may be an important characteristic of this antibiotic class with respect to
      safety of use in animals.

PMID- 12052188
TI  - Neuropeptide signaling systems - potential drug targets for parasite and pest
      control.
AB  - Current problems of drug resistance in parasites and pests demand the
      identification of new targets and their exploitation through novel drug design
      and development programs. Neuropeptide signaling systems in helminths (nematodes
      and platyhelminths = worms) and arthropods are well developed and complex, play a
      crucial role in many aspects of their biology, and appear to have significant
      potential as targets for novel drugs. The best-known neuropeptide family in
      invertebrates is the FMRFamide-related peptides (FaRPs). Amongst many roles,
      FaRPs potently influence motor function. The genome sequencing projects of
      Drosophila melanogaster and Caenorhabditis elegans have revealed unexpected
      complexity within the FaRPergic systems of arthropods and nematodes, although
      available evidence for platyhelminths indicates structural and functional
      simplicity. Regardless of these differences, FaRPs potently modulate motor
      function in arthropods, nematodes and platyhelminths and there appears to be at
      least some commonality in the FaRPergic signaling systems therein. Moreover,
      there is now increasing evidence of cross-phyla activity for individual FaRPs,
      providing clear signals of opportunities for target selection and the
      identification and development of broad-spectrum drugs.

PMID- 12052189
TI  - PF1022A and related cyclodepsipeptides - a novel class of anthelmintics.
AB  - Parasitic nematodes are a major cause of morbidity and mortality in man and also
      cause widespread loss of food production by infection of livestock. A milestone
      in the chemotherapy of nematode infections, especially in animals, was the
      discovery of the avermectins and milbemycins during the 1970s. Since the
      discovery of these highly active macrolides, reports of potent new classes of
      anthelmintics have been scarce. One of the most outstanding recently reported
      anthelmintics is the cyclooctadepsipeptide PF1022A, the most active member of a
      novel class of anthelmintic agents. During the past years several total syntheses
      of PF1022A and manifold structure-activity relationships have been established.
      Additionally, the biosynthesis of PF1022A has been elucidated and intensive
      investigations into the mode of action of this novel anthelmintic are underway.
      Comprehensive studies including cyclodepsipeptides with smaller ring-sizes, such
      as the enniatins, proved the PF1022 family and related cyclodepsipeptides to be
      the most promising follow-up candidates for the avermectins and milbemycins,
      which suffer from increasing nematode resistance.

PMID- 12052190
TI  - Marcfortine and paraherquamide class of anthelmintics: discovery of PNU-141962.
AB  - Three distinct chemical classes for the control of gastrointestinal nematodes are
      available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The
      relentless development of drug resistance has severely limited the usefulness of
      such drugs and the search for a new class of compounds   preferably with a
      different mode of action   is an important endeavor. Marcfortine A (1), a
      metabolite of Penicillium roqueforti, is structurally related to paraherquamide A
      (2), originally isolated from Penicillium paraherquei. Chemically the two
      compounds differ only in one ring; in marcfortine A, ring G is six-membered and
      carries no substituents, while in paraherquamide A, ring G is five-membered with
      methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to
      marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has
      excellent nematocidal activity, a superior safely profile, and is the first semi
      synthetic member of this totally new class of nematocides that is a legitimate
      candidate for development. This review describes the chemistry, efficacy and mode
      of action of PNU-141962.

PMID- 12052191
TI  - Molecular biology of serotonin receptors   structure and function at the
      molecular level.
AB  - 5-hydroxytryptamine (5-HT; serotonin) is a neurotransmitter essential for a large
      number of physiological processes including the regulation of vascular and non
      vascular smooth muscle contraction, modulation of platelet aggregation, and the
      regulation of appetite, mood, anxiety, wakefulness and perception. To mediate
      this astonishing array of functions, no fewer than 15 separate receptors have
      evolved, of which all but two (5-HT(3A) and 5-HT(3B)) are G-protein coupled
      receptors. This review will summarize our current understanding of the structure
      and function of the G-protein coupled 5-HT receptors. In particular, a systematic
      review of the available mutagenesis studies of 5-HT receptors will be presented.
      This information will be synthesized to provide a working model of agonist and
      antagonist actions at a prototypic 5-HT receptor the 5-HT(2A) receptor. Finally,
      examples will be given to demonstrate that a detailed knowledge of the predicted
      structure of one receptor can be useful for structure-based drug design.

PMID- 12052192
TI  - Constitutive activity of G-protein coupled receptors: emphasis on serotonin
      receptors.
AB  - Several lines of evidence indicate that G-protein coupled receptors (GPCR) may
      exist in a state that allows a tonic level of stimulation in vivo (constitutive
      activity). Several native forms of GPCR, when expressed in recombinant cell
      lines, display significant signal transduction stimulation in the absence of
      activating ligand. Many GPCR, including three serotonin receptors, display robust
      constitutive activation upon the mutation of a single amino acid, indicating
      mutations producing inappropriate constitutive activation may be etiological
      factors in diseases. If constitutive activity of GPCR is as common a phenomenon
      as some researchers suspect, this would suggest significant alterations in the
      classical model of ligand-receptor interactions. One of the most significant
      implications of constitutive activity for pharmacologists and medicinal chemists,
      is the possibility of developing drugs that lower the level of constitutive
      activity. Such compounds have been termed  inverse agonists . These drugs, in
      theory, would have different physiological effects, and therefore possibly
      different therapeutic potential, than classical competitive receptor antagonists
      ( neutral antagonists ). Theoretical issues concerning constitutive activity in
      the GPCR family and some of the evidence supporting the existence of constitutive
      activity in the GPCR family is reviewed. Studies are presented demonstrating the
      procedures for producing and characterizing constitutive activated forms of
      serotonin receptors, including the demonstration of inverse agonist activity of
      drugs on these receptors.

PMID- 12052194
TI  - Recent advances in 5-HT1B/1D receptor antagonists and agonists and their
      potential therapeutic applications.
AB  - The human 5-HT(1B) and 5-HT(1D) receptors are especially similar in sequence
      despite being encoded by two distinct genes. Although, human 5-HT(1B) and 5
      HT(1D) receptors have been pharmacologically differentiated using nonselective 5
      HT(1B/D) receptor antagonists such as ketanserin (1), ritanserin (2) and
      methiothepin (3), the precise function of these receptors remains undefined, and
      progress toward this has been hampered by the lack of selective ligands. The
      interest of the major pharmaceutical companies in 5-HT(1B/1D) antagonists
      increased by the discovery of potent and selective tools, combined with the fact
      that the blockade of terminal 5-HT(1B) receptors by selective antagonists has
      been proposed as a new approach for more efficient and/or fast-acting
      antidepressant drugs, since the acute blockade of these 5-HT autoreceptors will,
      in theory, immediately mimic their desensitization. Furthermore, it has been also
      suggested that supersensitive 5-HT(1B/1D) receptors may be involved in the
      pathophysiology of obsessive compulsive disorders (OCD). In the 5-HT(1B/1D)
      agonist field, since the discovery of sumatriptan (26) (a 5-HT(1B/1D) receptor
      agonist) as an effective treatment for migraine headache, intensive research in
      this area has led to several second-generation compounds, a few of which have
      either entered the market place or are in late clinical trials. Beside the
      antimigraine activity of the 5-HT(1B/1D) agonists in clinical evaluation or
      already on the market, other potential therapeutic evaluations (such as gastric
      motor effect, bipolar disorder, autism, anti-aggressive effects) with these drugs
      are being investigated. This article highlights and reviews the research advances
      published in the 5-HT(1B/1D) antagonist and agonist literature. The article is
      supplemented with selected references on the design, synthesis and development of
      novel 5-HT(1B/1D) agents, and on studies to understand their mechanism and
      pathophysiology. Emphasis is given to recent advances in the potential
      therapeutic applications of 5-HT(1B/1D) serotonergic agents. By no means has any
      attempt been made to exhaustively review the literature but rather, primary
      references along with citations to recent literature reviews have been included
      in each section.

PMID- 12052193
TI  - Ketanserin and spiperone as templates for novel serotonin 5-HT(2A) antagonists.
AB  - The structures of ketanserin (1) and spiperone (2) were examined in detail to
      determine the role of various substituent groups on 5-HT(2A) receptor affinity
      and selectivity. It was found that the presence of the quinazoline ring of
      ketanserin detracts from selectivity and that various ring-opened analogs
      displayed ketanserin-like affinity and up to 30-fold enhanced selectivity. The
      triazaspirodecanone portion of spiperone is a major determinant of its 5-HT
      affinity and selectivity. The conformational rigidity imposed by the ring, as
      well as the nature of the N(1)-substituent, are important factors in controlling
      binding at 5-HT(2A), 5-HT(2C), 5-HT(1A), and dopamine D2 receptors. Replacement
      of the N(1)-phenyl ring of spiperone with a methyl group (KML-010; 48) resulted
      in a compound that binds at 5-HT(2A) receptors with slightly lower affinity than
      spiperone, but that lacked affinity (Ki >10,000 nM) for 5-HT(2C) and 5-HT(1A)
      receptors and binds with 400-fold reduced affinity at D2 receptors.

PMID- 12052195
TI  - Application of ligand SAR, receptor modeling and receptor mutagenesis to the
      discovery and development of a new class of 5-HT(2A) ligands.
AB  - The present review describes our approach to the development of a structurally
      unique class of 5-HT(2A) ligands. On the basis of an abbreviated graphics model
      of a 5-HT(2A) serotonin receptor, it was hypothesized that introduction of an
      additional aromatic ring might enhance the affinity of phenylethylamine (an agent
      that lacks significant affinity for the 5-HT(2A) receptors). Continued work with
      such structures, and the continual refinement of graphics receptor models,
      ultimately led to the identification of AMDA (27, 5-HT(2A) K(i) = 20 nM). AMDA is
      a 5-HT(2A) antagonist that, unlike certain other tricyclic 5-HT(2A) antagonists,
      binds with very low affinity at dopamine D(2) receptors, the serotonin
      transporter, and the norepinephrine transporter. Comparative structure-affinity
      studies indicate that AMDA binds in a manner distinct from the tricyclic
      antagonists Graphics models were employed to identify possible modes of binding.
      This investigation illustrates the impact of a combination of classical medicinal
      chemistry, receptor modeling, and molecular biology on novel drug design.

PMID- 12052196
TI  - The Interactions of the 5-HT(3) receptor with arylpiperazine, tropane, and
      quinuclidine ligands.
AB  - The serotonin 5-HT(3) receptor subtype is unique among the receptors for this
      neurotransmitter because it has been demonstrated to be a ligand-gated ion
      channel capable of mediating rapid intercellular communication. This review
      covers the authors work performed during more than a decade in the development of
      5-HT(3) receptor ligands belonging to the classes of arylpiperazines, tropanes,
      and quinuclidine derivatives. The discussion is focused mainly on what the
      authors have learned about the interaction of these structurally different
      ligands with their receptor and shows the way their ideas evolved along with the
      progress of the project. Furthermore, a summary of the most significant structure
      affinity relationships, derived from the original work, is reported to support
      the discussion.

PMID- 12052198
TI  - Memories are made of this (perhaps): a review of serotonin 5-HT(6) receptor
      ligands and their biological functions.
AB  - The possible role of 5-HT(6) receptor antagonists in the treatment of learning
      and memory disorders has stimulated significant recent work in this area. The
      first selective antagonists of this receptor were identified by Roche (Ro 04-6790
      and Ro 63-0563) and SmithKline Beecham (SB-271046), although they only had poor
      to modest brain penetration, respectively. Recently, several structurally
      different series of selective antagonists have been reported. Glennon s group and
      Merck Sharp & Dohme have discovered N,N-dimethyl-1-benzenesulfonyl-5-methoxytrypt
      amine as a reasonably selective, high affinity antagonist, while Allelix have
      gone on to find that a 6-bicyclopiperazinyl-1-naphthylsulfonylindole had improved
      affinity and selectivity. Roche have reported subsequently on more lipophilic
      analogs of Ro 04-6790 that appear to penetrate the brain better. Reversing the
      sulfonamide linkage of SB-271046 led to a new series of compounds, producing SB
      357134, which also had increased CNS penetration. A series of selective partial
      agonists containing a 4-piperazinylquinoline system has also been described.
      Recent studies in the Morris water maze with both Ro 04-6790 and SB-271046 have
      concluded that 5-HT(6) receptor antagonists improved retention performance,
      although these results are open to interpretation. Other behavioural studies have
      also implicated a role for 5-HT(6) in cognition enhancement and this has been
      supported by in vivo microdialysis studies that showed SB-271046 produced an
      increase in extracellular glutamate levels in the frontal cortex. However, we
      have been unable to replicate these effects with either SB-271046 or Ro 04-6790,
      and clearly further work is required before we can be certain of the functional
      role of this receptor.

PMID- 12052197
TI  - 5-HT(4) receptor antagonists: structure-affinity relationships and ligand
      receptor interactions.
AB  - Among serotonin receptors (5-HTRs), the 5-HT(4) subtype is of considerable
      interest because it is involved in (patho)physiological processes both in
      peripheral and central nervous systems. In addition to the clinical use of 5
      HT(4R) agonists in the treatment of gastrointestinal motility disorders, the
      potential use of antagonists in the treatment of irritable bowel syndrome,
      arrhythmias and micturition disturbances are currently under investigation. This
      article will review the development of the most important classes of 5-HT(4R)
      antagonists with an emphasis on benzimidazole derivatives, their structure
      affinity relationships, ligand-receptor interactions and pharmacological
      applications.

PMID- 12052200
TI  - Molecular mapping in the CNS.
AB  - Since ancient times the operation of the brain has elicited more than usual
      interest. Data mining of the human genome is revealing that many CNS
      abnormalities have a genetic component. As yet this information can not be used
      directly to cure or ameliorate specific CNS disorders although this is regarded
      as having great potential for future therapies. Current CNS drug design and 3D
      QSAR is based on knowing either the structures of key proteins and how smaller
      molecules interact with them to obtain a pharmacological response, or on
      hypothesising about key structural features and interactions by a variety of
      molecular modelling and computational techniques. Methods used include
      conformational analyses, pharmacophore development and QSAR which are now being
      actively applied to increase our understanding of how molecules interact with
      specific sites within the CNS as a basis for the design of new pharmacologically
      active compounds. In this review we give an overview of the latest strategies
      used in 3D-QSAR based drug design and survey the most recent applications of
      these strategies to the CNS. By way of example, accounts are given of computer
      based research aimed at drugs targeting GABA, glutamate, dopamine and opioid
      receptors.

PMID- 12052199
TI  - The use of computational methods in the discovery and design of kinase
      inhibitors.
AB  - The recent success of the first FDA-approved small-molecule tyrosine kinase
      inhibitor Gleevec (STI-571, imatinib mesylate) in the treatment of chronic
      myelogenous leukemia (CML) has focused attention on the potential therapeutic
      usefulness of inhibitors of other kinase targets. This review shall highlight
      recent applications of computational chemistry methods, comprising both ligand
      based and structure-based approaches, in the discovery and design of kinase
      inhibitors. In particular, we will focus on ATP-competitive inhibitors of
      selected kinase targets of therapeutic importance.

PMID- 12052201
TI  - Protein flexibility is an important component of structure-based drug discovery.
AB  - Receptor-based drug discovery can increase the novelty of a hit list over ligand
      based models that are dependent on known inhibitors. It is important to explore
      new conformational and chemical space, but it is difficult to predict the
      plasticity of the binding site. Receptor-based methods are usually based on
      crystal structures of ligand-protein complexes, and hit lists can be restricted
      to the size and shape of the receptor model. Many improvements that accommodate
      protein flexibility in computer-aided drug design are being developed. These
      methods are reviewed with the focus being techniques that move beyond the
      rotation of side chains. The use of multiple protein structures is emerging as
      the best choice for including more realistic changes in protein conformation, but
      the optimal way to using these structures is still unclear.

PMID- 12052202
TI  - Molecular dynamics simulation for ligand-receptor studies. Carbohydrates
      interactions in aqueous solutions.
AB  - The review deals with the problem of the study of ligand-receptor interactions
      and the use of Molecular Dynamics (MD) simulation to approach such a problem.
      After a short review of the fundamentals of MD we describe the medium in which
      all biology takes place, water. Emphasis is put on the water models appropriate
      for simulation of macromolecular systems explicitly including the water
      molecules. We consider the quality of the water model both in terms of simplicity
      and performance to describe the liquid water properties. Heavy water, although
      not a biologically viable medium, is considered since many experiments make use
      of it as a solvent. Sweetness of carbohydrates is considered as an example of the
      procedure suitable to characterize active sites on the ligands. Consideration is
      given to the computation of the binding constants through molecular dynamics. The
      computation of the Free Energy is described and illustrated. The potentiality of
      MD for studies of ligand-receptor interactions is limited by the computer
      resources, for even with large computing facilities the need of relatively long
      simulation times severely restricts the study of large systems. A method is
      described in which several shells are treated at different levels of
      approximation, form mechanical response and mean electrical field to quantum
      mechanics, through stochastic dynamics and atomic classical MD. The review closes
      with a brief account of the perspectives of the method.

PMID- 12052203
TI  - Dynamic QSAR techniques: applications in drug design and toxicology.
AB  - The basic principles of 3-D quantitative structure-activity relationships (QSARs)
      analysis are discussed in the light of the fuzzy logic concept. According to that
      concept, the traditionally  one chemical - one structure - one parameter value 
      relationship in QSAR is suggested to be modified into  one chemical   finite set
      of structures - range of parameter values  principle. In this respect, two
      recently developed techniques accounting for conformational flexibility in 3-D
      QSARs are reviewed. A basic assumption underlying both methods is that chemical
      behavior in complex biological systems is context-dependent. A molecule can exist
      and interact in a variety of conformations depending on the specificity of the
      endpoint under investigation and reaction media. It was demonstrated that
      selection of  active  conformer(s) in QSAR studies is a task as important as the
      selection of relevant molecular parameters. Specifically selected  active 
      conformers, rather than the lowest-energy states of the chemicals are suggested
      to be used in the correlative QSARs. The method for recognition the common
      reactivity pattern (COREPA) of structurally heterogeneous compounds that elicit
      similar biological behaviour is based on all energetically reasonable conformers
      of chemicals. The principle assumption of the method is that biologically similar
      chemicals should possess a commonality in their stereoelectronic (reactivity)
      pattern. Originally developed algorithms for conformer generation are presented
      in association with the QSAR methods accounting for conformational flexibility of
      chemicals. Applicability of the QSAR technique for selection active conformers is
      illustrated by presenting QSAR models derived for Ah binding affinity of PCBs and
      antimicrobial activity of rifamicin derivatives. Models for predicting estrogenic
      activity of structurally diverse chemicals and ACE inhibition exemplified the
      applicability of the COREPA method. The model performance is analyzed by the 3D
      screening exercise of large chemical inventories with subsequent experimental
      validation within the EDAEP project. Besides the impact of conformational
      flexibility of chemicals in 3D QSAR the role of different molecular descriptors
      is discussed with respect to their ability to describe molecular interactions
      with different specificity.

PMID- 12052204
TI  - Positron emission tomography and brain monoamine neurotransmission -- entries for
      study of drug interactions.
AB  - Monoamine neurotransmission is a complicated process with interactions between
      individual neurotransmitter pathways, multiple receptors with different responses
      and a variety of feedback loops regulating neurotransmitter synthesis, release,
      reuptake and effect on receptors. The system is further affected by a range of
      enzymes with co-factors controlling synthesis and degradation of monoamines.
      Positron emission tomography (PET) has evolved to a very versatile tool for the
      in vivo imaging and characterisation of physiology and biochemistry. The basis
      for its expansion during the last years has been a rapid development of labelling
      methods, allowing a range of tracer molecules to be generated and used in human
      and research animal studies. The most important PET radionuclide is (11)C with a
      short half-life of approximately 20 minutes. This radionuclide is ideal for the
      labelling of organic molecules and for multi-tracer applications in research and
      drug development studies. PET has been used for a range of explorative studies on
      the monoamine neurotransmission, as exemplified by studies on the expression of
      dopamine and serotonin receptors as well as the rate of dopamine and serotonin
      synthesis. The present article gives examples of studies where PET has been used
      for the characterization of monoamine transmitter systems in experimental animals
      and in humans, both in healthy individuals and in patients with diseases
      affecting neurotransmission.

PMID- 12052205
TI  - Scintigraphic imaging of HSVtk gene therapy.
AB  - The evolution of molecular biology has enabled the exploration of novel
      sophisticated gene-directed treating modalities for cancer. Suicide gene therapy 
      i.e. transfection of a so-called suicide gene that sensitizes target cells
      towards a prodrug - may offer an attractive approach to treat malignant tumors.
      For the development of effective clinical suicide gene therapy protocols, a non
      invasive method to assay the extent, the kinetics and the spatial distribution of
      transgene expression is essential. This would allow investigators and physicians
      to assess the efficiency of experimental and therapeutic gene transfection
      protocols and would enable early prognosis of therapy outcome. Radionuclide
      imaging techniques like single photon emission computed tomography (SPECT) and
      positron emission tomography (PET), which can non-invasively visualize and
      quantify metabolic processes in vivo, are being evaluated for repetitive
      monitoring of transgene expression in living animals and humans. Transgene
      expression can be monitored directly by imaging the expression of the therapeutic
      gene itself, or indirectly using a reporter gene that is coupled to the
      therapeutic gene. Various radiopharmaceuticals have been developed and are now
      being evaluated for imaging of transgene expression. This review surveys the
      progress that has been made in the field of non-invasive nuclear imaging of
      transgene expression and focuses on the herpes simplex virus type 1 thymidine
      kinase (HSVtk) gene therapy approaches.

PMID- 12052207
TI  - Medical imaging techniques in the evaluation of strategies for therapeutic
      angiogenesis.
AB  - Recent advancements in our understanding of the basic biology of angiogenesis
      have prompted a focus on practical applications, both in cardiovascular disease
      and in oncology. The focus on practical applications has stimulated development
      of novel noninvasive tools that provide serial assessment of ongoing vessel
      growth in vivo. Nuclear imaging (SPECT, PET) and x-ray angiography have been used
      to assess changes in perfusion and anatomic appearance, respectively, after
      induced neovascular development. New MRI techniques provide the ability to
      identify early changes in vivo that are more sensitive to detection of the
      effects of new vessel growth than x-ray angiography or nuclear imaging. These new
      MRI techniques include measurement of blood delivery to the myocardium,
      development of intramyocardial vasculature, and incremental changes in regional
      myocardial contractile function. With the combination of methods now available,
      we expect to be able to track key steps of angiogenesis in vivo and to assess the
      efficacy of angiogenic therapies. These new imaging capabilities offer crucial
      information which we hope will hasten the identification and deployment of
      effective pharmaceutical therapies as an adjunct or alternative to invasive
      treatments of ischemic disease by targeted stimulation of angiogenesis, and of
      cancer, by targeted inhibition of angiogenesis.

PMID- 12052206
TI  - Labelled oligonucleotides as radiopharmaceuticals: pitfalls, problems and
      perspectives.
AB  - The labelling of single-stranded oligonucleotides with a positron or single
      photon emitter can result in valuable radiopharmaceuticals with promising
      applications for: (i) Imaging of specific mRNAs, i.e. visualisation of the
      expression of specific genes in vivo (ii) Monitoring of antisense chemotherapy,
      i.e. measuring the efficiency of efforts to block the expression of specific
      genes; (iii) Gene radiotherapy, i.e. the targeting of radiation damage to
      specific DNA sequences in order to destroy tumours; (iv) Imaging of protein
      targets by the use of aptamer oligonucleotides, i.e. oligonucleotide ligands
      obtained by in vitro evolution of selection-amplification steps, or selected for
      their interaction with nucleic acid-binding proteins; (v) Pre-targeting
      strategies based on the specificity of complementary sequence hybridisation.
      Nevertheless, oligonucleotides are intrinsically poor pharmaceuticals because of
      their large size, low stability, poor membrane passage and a number of
      undesirable and sometimes unpredictable side effects. As an alternative to the
      inherently unstable phosphodiester DNAs, chemically modified oligonucleotides
      such as phosphorothioate, methylphosphonate and peptide nucleic acid oligomers
      have been developed, and some are in clinical trials for the chemotherapy of
      several types of tumours. Imaging techniques could be useful in the development
      of such therapies. In addition, the potential of targeting virtually any disease
      or physiological process, by changing only the sequence of the oligomer, could
      provide a means to identify serious diseases in a very early stage, and be a
      highly specific modality to diagnose and differentiate various cancers. This has
      stimulated efforts to develop such radiopharmaceuticals in many laboratories, and
      encouraging results have been reported using technetium-99m, indium-111, carbon
      11, fluorine-18, bromine-76 and iodine-125 labelled oligonucleotides.

PMID- 12052208
TI  - Dedicated small animal scanners: a new tool for drug development?
AB  - Nuclear imaging techniques can provide information about the time course of
      uptake, the spatial distribution, and the functional effects of a drug in the
      human body. Recently, PET has also acquired the potential to affect the drug
      development process during a very early stage, when a drug is undergoing animal
      testing. The development of dedicated small animal scanners with high resolution
      has made it possible to assess the time course of uptake of a drug within a
      single animal, providing that the drug is labelled with a positron-emitting
      isotope. Dedicated small animal scanners may therefore prove to be very useful,
      especially in those parts of the drug development process that require a
      longitudinal study design. However, in the case of receptor and enzyme studies,
      there may be pharmacological constraints and specific radioactivity of the
      radiopharmaceuticals may become an important issue. This paper will assess the
      potential and also the limitations of high-resolution PET in animal testing of
      therapeutic drugs.

PMID- 12052209
TI  - Fundamentals of quantitative PET data analysis.
AB  - Drug analysis and development with PET should fully exhaust the ability of this
      tomographic technique to quantify regional tracer concentrations in vivo. Data
      evaluation based on visual inspection or assessment of regional image contrast is
      not sufficient for this purpose since much of the information present in
      dynamically acquired data is not used by these approaches. Compartment modelling
      of dynamic PET data is generally the method of choice since it allows a
      quantitative assessment of the underlying pharmacokinetic parameters describing
      drug transport, metabolism and molecular interactions. We present here an
      overview of key issues of compartment modelling with specific attention to the
      assumptions underlying the various models and their limitations. We believe that
      a thorough understanding of the applicability of models is mandatory for the
      development, successful execution and analysis of quantitative PET studies.
      Otherwise, meaningful and interpretable results will often not be obtained.

PMID- 12052210
TI  - Antiangiogenic, bioreductive and gene therapy approaches to the treatment of
      hypoxic tumours.
AB  - Quinone based bioreductive drugs have, potentially, a very versatile use in
      cancer chemotherapy. They can be activated by DT-diaphorase and hence can be used
      to target tumour types rich in this (O2)-independent reductase enzyme. Small
      molecular modifications can substantially reduce specificity for DT-diaphorase
      and under these circumstances the quinones become much less toxic in air but
      retain their potent cytotoxic effects under hypoxic conditions. Our understanding
      of the reductive (bio) chemistry of indolequinones, in particular, has
      subsequently allowed us to develop a platform technology where almost any
      therapeutic entity can potentially be delivered, selectively, to hypoxic tumours.
      Antiangiogenic approaches are currently receiving a substantial amount of
      attention and this review brings their development into context in view of the
      hypoxia dependence for neovascularization. Lastly, the use of bioreductive drugs
      when combined with hypoxia-mediated gene therapy is described. Such an approach
      provides a unique dual level of specificity for targeting hypoxic tumours and
      potentially can provide substantial therapeutic benefit.

PMID- 12052211
TI  - Tumour cytochrome P450 and drug activation.
AB  - The expression of drug metabolising cytochrome P450s (CYPs) notably 1A, 1B, 2C,
      3A, 2D subfamily members have been identified in a wide range of human cancers.
      Individual tumour types have distinct P450 profiles as studied by detection of
      P450 activity, identification of immunoreactive CYP protein and detection of CYP
      mRNA. Selected P450s, especially CYP1B1, are overexpressed in tumours including
      cancers of the lung, breast, liver, gastrointestinal tract, prostate, bladder.
      Several prodrug anti-tumour agents have retrospectively been identified as P450
      substrates for which tumour CYP activation may hitherto have been underestimated.
      Those in clinical use include prodrug alkylating agents (cyclophosphamide,
      ifosphamide, dacarbazine, procarbazine), Tegafur, a prodrug fluoropyrimidine,
      methoxymorphylinodoxorubicin, a metabolically activated anthracycline, as well as
      flutamide and tamoxifen, two non-steroidal hormone receptor antagonists that are
      significantly more active following CYP-hydroxylation. More exciting is the
      prospect of developing new agents designed to be selectively dependent on tumour
      CYP activation. This can be illustrated with P450 activation of the 2-(4
      aminophenyl)benzothiazoles exclusively in CYP1A1 inducible tumours. Also of
      interest is the bioreductive antitumour prodrug AQ4N, a CYP3A substrate that is
      activated to a cytotoxic metabolite specifically in hypoxic tumour regions.

PMID- 12052212
TI  - Nitroreductase-based GDEPT.
AB  - Nitroreductases that metabolise aromatic nitro groups to hydroxylamines are
      attractive as enzymes for GDEPT because of the very large electronic change that
      this metabolism generates, providing an efficient  switch  that can be exploited
      to generate potent cytotoxins. While nitroreductase enzymes are widespread,
      nearly all the work using these in GDEPT has been with the nfsB gene product of
      Escherichia coli, an oxygen-insensitive flavin mononucleotide nitroreductase
      (NTR). Four classes of prodrugs for NTR have been described;
      dinitroaziridinylbenzamides, dinitrobenzamide mustards, 4-nitrobenzylcarbamates
      and nitroindolines. While some quinones are excellent substrates for NTR, none
      have been identified as potential GDEPT prodrugs. The most widely studied prodrug
      used for GDEPT in conjunction with NTR is the dinitroaziridinylbenzamide CB 1954.
      This shows high selectivity (>1000-fold) in cell lines transfected with NTR, has
      potent and long-lasting inhibition of NTR-transfected tumours in mice, and is in
      Phase I trial in conjunction with virally-delivered NTR enzyme. The related
      mustard SN 23862 has similar selectivity and superior bystander effects in animal
      models. Nitrobenzyl carbamates of a variety of cytotoxic amines (including
      aniline mustards, enediynes, duocarmycin analogues, pyrrolobenzodiazepines and
      the antitumour antibiotics doxorubicin, actinomycin D and mitomcyin C) are
      metabolised efficiently by NTR to the hydroxylamines, that fragment to release
      the amines. Nitroindoline derivatives of duocarmycins also show moderate
      selectivity for NTR-transfected cell lines in culture.

PMID- 12052213
TI  - Indole-3-acetic acids and horseradish peroxidase: a new prodrug/enzyme
      combination for targeted cancer therapy.
AB  - The radical-cations formed on one-electron oxidation of indole-3-acetic acid
      (IAA) and its ring-substituted derivatives rapidly fragment, eliminating carbon
      dioxide from the sidechain and forming a carbon-centred free radical (3
      indolylmethyl or skatolyl, or analogues). This radical is reactive towards DNA
      and possibly other targets in anoxia, but in oxic or hypoxic cells rapidly adds
      oxygen to form a peroxyl radical. Subsequent products include 3-methylene-2
      oxindole or analogues, reactive towards cellular nucleophiles such as thiols and
      DNA. The one-electron oxidation of indole-3-acetic acids is efficiently achieved
      by horseradish peroxidase (HRP), not requiring added hydrogen peroxide cofactor.
      The combination of IAA and HRP is cytotoxic towards mammalian cells, including
      human tumour cells. Unexpectedly, some halogen-substituted derivatives of IAA are
      very cytotoxic with HRP even though they are more difficult to oxidize. IAA is
      tolerated by humans in high doses and HRP is a robust enzyme meeting many of the
      requirements for targeting to tumours by coupling to antibodies or polymers, or
      by gene transfection. It is suggested that the indole acetic acids merit further
      evaluation as potential prodrugs for use in cancer therapy based on targeted
      delivery of HRP to tumours.

PMID- 12052214
TI  - Duocarmycins--natures prodrugs?
AB  - The duocarmycins and (+)-CC-1065 are amongst the most potent antitumour
      antibiotics discovered to date and yet have not progressed into the clinic. The
      natural products are extremely stable to nucleophilic attack until bound to their
      DNA target and are not substrates for any other biological nucleophile. The
      mechanism for this target activation of the duocarmycins is discussed with
      relation to both an acid-catalyzed activation and a binding-induced
      conformational change leading to ground state destabilization. It is suggested
      that targeting of the duocarmycins to their site of action in a tumour may be
      more important than introducing systemically-activated prodrugs as the natural
      product itself can be considered to be a type of prodrug, activated only on
      binding to its targets. Methods that have been used to target CC-1065 and the
      duocarmycins are reviewed as well as efforts towards systemically activated
      prodrugs. A simple analysis of the approaches that could be taken to vary the
      structure for targeting is suggested.

PMID- 12052215
TI  - Beta-glucuronidase-mediated drug release.
AB  - The selective activation of a relatively non-toxic prodrug by an enzyme present
      only in the tumour should enhance the drug concentration at the tumour site and
      result in a better anti-tumour effect and a reduction in systemic toxicity as
      compared to conventional chemotherapy. beta-Glucuronidase is such an enzyme. It
      is normally expressed in the lysosomes of cells. In larger tumours, however, high
      levels of the enzyme are present in necrotic areas. Several glucuronide prodrugs
      have been synthesised that can be activated by beta-glucuronidase. They are
      relatively non-toxic due to their hydrophilic nature, which prevents them from
      entering cells and thus from contact with lysosomal beta-glucuronidase. The main
      problem of glucuronide prodrugs for clinical use is their fast renal clearance.
      Special attention should be paid to the development of new less hydrophilic
      prodrugs with slower clearance, as this would result in a prolonged exposure to
      beta-glucuronidase at the site of the tumour and a reduction of the amount of
      prodrug needed. A number of interesting anthracyclin-based glucuronide prodrugs
      have been synthesised and have shown favourable therapeutic effects compared to
      treatment with the parent drug. The tumoural levels of beta-glucuronidase can
      even be enhanced by two-step approaches, in which exogenous enzyme is targeted to
      the tumour by an antibody (ADEPT) or by the gene encoding the enzyme in
      transduced tumour cells (GDEPT). The ADEPT and GDEPT approaches in combination
      with glucuronide prodrugs have shown enhanced efficacy in experimental tumour
      models. Further improvement of ADEPT and GDEPT is warranted to optimise the
      tumour uptake and retention of antibody-enzyme fusion proteins and the efficiency
      and safety of current gene delivery methods. In conclusion, it is clear that
      glucuronide prodrugs hold promise for future use in the treatment of cancer in
      patients as monotherapy. Enhancement of the therapeutic effects of glucuronide
      prodrugs, also in patients with small tumour lesions, may possibly be achieved by
      techniques that target beta-glucuronidase specifically to the site of the tumour.

PMID- 12052216
TI  - Cytochrome P450 gene-directed enzyme prodrug therapy (GDEPT) for cancer.
AB  - Several commonly used cancer chemotherapeutic prodrugs, including
      cyclophosphamide and ifosfamide, are metabolized in the liver by a cytochrome
      P450 (CYP)-catalyzed prodrug activation reaction that is required for therapeutic
      activity. Preclinical studies have shown that the chemosensitivity of tumors to
      these prodrugs can be dramatically increased by P450 gene transfer, which confers
      the capability to activate the prodrug directly within the target tissue. This
      P450 gene-directed enzyme prodrug therapy (P450 GDEPT) greatly enhances the
      therapeutic effect of P450-activated anti-cancer prodrugs without increasing host
      toxicity associated with systemic distribution of active drug metabolites formed
      by the liver. The efficacy of P450 GDEPT can be enhanced by further increasing
      the partition ratio for tumor:liver prodrug activation in favor of increased
      intratumoral metabolism. This can be achieved by co-expression of P450 with the
      flavoenzyme NADPH-P450 reductase, which increases P450 metabolic activity, by
      localized prodrug delivery, or by the selective pharmacologic inhibition of liver
      prodrug activation. P450 GDEPT prodrug substrates are diverse in their structure,
      mechanism of action, and optimal prodrug-activating P450 gene; they include both
      established and investigational anticancer prodrugs, as well as bioreductive
      drugs that can be activated by P450/P450 reductase in a hypoxic tumor
      environment. Several strategies may be employed to achieve the tumor-selective
      gene delivery that is required for the success of P450 GDEPT; these include the
      use of tumor-targeted cellular vectors and tumor-selective oncolytic viruses.
      Overall, P450-based GDEPT presents several important, practical advantages over
      other GDEPT strategies that should facilitate the incorporation of P450 GDEPT
      into existing cancer treatment regimens. A recent report of clinical efficacy in
      a P450-based phase I/II gene therapy trial for pancreatic cancer patients
      supports this conclusion.

PMID- 12052217
TI  - The impact of fatty acid oxidation on energy utilization: targets and therapy.
AB  - Utilization of fat as a long-term energy storage vehicle is crucial for the
      maintenance of cellular metabolism and is under intricate and many times
      redundant control mechanisms. Aberrations in the control of energy metabolism is
      apparent in diseases such as diabetes and obesity and is evident early on in
      patients with impaired glucose tolerance. Insulin resistance has been observed at
      the level of muscle, liver and adipose tissue. Hyperglycemia is the hallmark of
      diabetes and is characterized by decreased glucose disposal and increased glucose
      production, driven by enhanced and uncontrolled fatty acid oxidation (FAO).
      Mechanisms aimed at limiting the availability of substrates or the activity of
      processes involved in FAO should provide an immediate reduction in undesired
      glucose production in these individuals. Numerous targets are available which
      influence directly the metabolism of fat, including limiting availability of
      substrate to FAO, inhibiting oxidation of the fatty acid per se, and uncoupling
      the energy obtained during the oxidation of the fatty acid. These include
      antilipolytic agents which limit the availability of substrate, FAO inhibitors
      which limit fatty acid transport (carnitine palmitoyl transferase, CoA
      sequestration), FAO per se (beta oxidation), and agents which uncouple the energy
      of FAO (uncoupling proteins, beta3 agonists). These other targets which affect
      fatty acid metabolism indirectly will be discussed in this review with 184
      references.

PMID- 12052218
TI  - Alpha 4 integrin antagonists.
AB  - The accumulation of leukocytes in various organs contributes to the pathogenesis
      of a number of human autoimmune diseases such as asthma, rheumatoid arthritis,
      Crohn s disease, ulcerative colitis, hepatitis C, and multiple sclerosis. The
      inflammatory processes leading to tissue damage and disease are mediated in part
      by the alpha4 integrins, alpha4beta1 and alpha4beta7, expressed on the leukocyte
      cell surface. These glycoprotein receptors modulate cell adhesion via interaction
      with their primary ligands, vascular cell adhesion molecule (VCAM) and mucosal
      addressin cell adhesion molecule (MAdCAM), expressed in the affected tissue. Upon
      binding, the combined integrin/CAM interactions at the cell surface result in
      firm adhesion of the leukocyte to the vessel wall followed by entry into the
      affected tissue. Elevated cell adhesion molecule (CAM) expression in various
      organs has been linked with several autoimmune diseases. Monoclonal antibodies
      specific for alpha4 integrins or their CAM ligands can moderate inflammation in
      animal models suggesting such inhibitors may be useful for treating human
      inflammatory diseases. The alpha4 integrins have become well validated drug
      targets for pharmaceutical companies and numerous publications describing alpha4
      integrin antagonists have recently appeared. This article discusses the rationale
      for targeting alpha4 integrins for the treatment of autoimmune disorders and
      reviews some currently known antagonists. The methods used to identify lead
      molecules and the progress of selected antagonists toward becoming new drugs will
      is also discussed. (131 references).

PMID- 12052219
TI  - Recent advances in PDE4 inhibitors as immunoregulators and anti-inflammatory
      drugs.
AB  - The phosphodiesterases (PDEs) are responsible for the hydrolysis of intracellular
      cyclic adenosine and guanosine monophosphate (cAMP and cGMP, respectively). They
      are classified into 11 major families (PDE1-11) and the type 4 phosphodiesterase
      (PDE4) is a cAMP-specific enzyme localized in airway smooth muscle cells as well
      as in immune and inflammatory cells. The PDE4 activity is associated with a wide
      variety of diseases some of which have been related to an inflammatory state,
      (e.g. asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis
      (RA)) while others have recently been connected to autoimmune pathology.
      Therefore, an intense effort toward the development of PDE4 inhibitors has been
      generated for the last decade. Unfortunately, the effects of prototype PDE4
      inhibitors have been compromised by side effects such as nausea and emesis and
      the clinical use of those compounds is still limited. Several companies have
      focused on the design of a new generation of PDE4 inhibitors dissociating
      beneficial activity and adverse effects. This review highlights the recent data
      of the most advanced clinical candidates, the design and structure activity
      relationships of the recent structural series reported in the literature over the
      last two years, as well as recent advances in the multiple therapeutic
      indications of PDE4 inhibitors (a review with 375 references).

PMID- 12052220
TI  - Macrophage migration inhibitory factor and the discovery of tautomerase
      inhibitors.
AB  - Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine
      released from T-cells and macrophages, and is a key molecule in inflammation.
      Although a detailed understanding of the biological functions of MIF has not yet
      been found, it is known that MIF catalyzes the tautomerization of phenylpyruvate
      and a non-physiological molecule, D-dopachrome. A potent tautomerase inhibitor
      would be expected, as a validation tool, to shed light on role of MIF activity
      and the relationship between its biological and enzymatic activity. Such
      tautomerase inhibitors would be useful in the treatment of MIF-related diseases,
      such as sepsis, acute respiratory distress syndrome (ARDS), asthma, atopic
      dermatitis, rheumatoid arthritis (RA), nephropathy and tumors. In this review, we
      have focused on (1) the biological and enzymatic activities of MIF, (2) the
      discovery of novel, drug-like tautomerase inhibitors of MIF using a structure
      based computer-assisted search, and (3) a crystallographic and molecular modeling
      study of the MIF-tautomerase inhibitor complexes (A review with 133 references).

PMID- 12052221
TI  - Genomics and the prospects for the discovery of new targets for antibacterial and
      antifungal agents.
AB  - The current increase in the number of microbes resistant to antibacterial or
      antifungal agents represents a potential crisis in human and veterinary medicine.
      Some believe that we are entering a post-antibiotic era where most antibiotics no
      longer will be efficacious. Therefore, it is important that new antibiotics be
      developed. However, because of the potential for cross-resistance, new targets
      for the discovery of antibiotics are needed particularly where resistance does
      not currently exist. The results obtained from the sequencing of genomes from
      pathogenic bacterial and fungal microbes provide an opportunity to ameliorate
      this problem. Genomic sequence data can be used to identify new genes that could
      be used as targets for new antibiotic discoveries. Viable new target genes might
      represent those that are widely distributed among pathogens or that have homologs
      and are essential for the viability of the organism. Chemical compounds that
      attack such targets would be expected to have classical antibiotic activities.
      Less widely distributed genes still could be valuable targets for narrow spectrum
      antibiotics. While many of these genes will have known or putative functions
      based on DNA sequence homology, the most interesting genes are the newly
      discovered genes with unknown functions. In this paper, it is suggested that
      novel, non-traditional targets also will be found through the analysis of genome
      sequences: those that are involved in disease pathogenesis and those that are
      involved in adaptation and growth in infection sites. The advantage of the non
      classical targets is that targeting these sites may not result in the same degree
      of selective pressure that encourages resistance, and these could have a longer
      therapeutic life time.

PMID- 12052222
TI  - Genomics in anti-infective drug discovery--getting to endgame.
AB  - Whole chromosome sequence of prokaryotes has provided the availability of
      multiple bacterial pathogen sequence data and it has become a widely used tool in
      the drug discovery process. However the sequence data in itself is merely a
      starting point for drug discovery of novel antibacterial targets and, eventually,
      drugs. In order to leverage this large amount of data it is necessary to match an
      understanding of the microbial physiology of pathogenic bacteria to disease
      processes and identifying the gene products for which intervention may reduce or
      eliminate the infectious state. However, to date, the application of genomics to
      anti-infective drug discovery has not, since 1995 with the first complete
      sequence of a pathogenic bacterium, led to identification of a novel
      antibacterial agent. Here we review the field of bacterial genomics and how it is
      enabling the drug discovery process. Many new molecular-based technologies
      (proteomics, transcriptional profiling, studies of gene expression in vivo) have
      originated or have expanded into wider use, and have been made possible by the
      availability of complete bacterial genome sequence information and subsequent
      bioinformatic analytic tools. Taken together, these technologies, overlaid within
      an established drug discovery program, now affords the opportunity for the
      identification, validation, and process design for high-throughput target mining
      at unprecedented volumes and timeframes.

PMID- 12052223
TI  - Microbial genomics and novel antibiotic discovery: new technology to search for
      new drugs.
AB  - The process of prokaryotic drug discovery has been a model of success for over
      fifty years, yet the number of exploited bacterial targets is a mere fraction,
      less than 0.1% of the potential targets (based on total number of bacterial genes
      identified by gene sequence projects). To better understand the potential for
      drug intervention, multiple paradigms have been established in the pharmaceutical
      industry, all with some semblance of commonality and uniqueness to provide
      proprietary positioning, yet no company has been successful to date in taking a 
      genomics approach  to the finish line of having a genomics-based drug on the
      market. Within this overview, we provide a strategic overview of a sample process
      for the identification, validation and exploitation of novel antibacterial
      targets ascertained through a bioinformatics-based genomics drug discovery
      program.

PMID- 12052224
TI  - Genomics strategies for antifungal drug discovery--from gene discovery to
      compound screening.
AB  - The use of genomics tools to discover new genes, to decipher pathways or to
      assign a function to a gene is just beginning to have an impact. Genomics
      approaches have been applied to both antibacterial and antifungal target
      discovery in order to identify a new generation of antibiotics. This review
      discusses genomics approaches for antifungal drug discovery, focusing on the
      areas of gene discovery, target validation, and compound screening. A variety of
      methods to identify fungal genes of interest are discussed, as well as methods
      for obtaining full-length sequences of these genes. One approach is well-suited
      to organisms having few introns (Candida albicans), and another for organisms
      with many introns (Aspergillus fumigatus). To validate broad spectrum fungal
      targets, the yeast Saccharomyces cerevisiae was used as a model system to rapidly
      identify genes essential for growth and viability of the organism. Validated
      targets were then exploited for high-throughput compound screening.

PMID- 12052225
TI  - Comprehensive essential gene identification as a platform for novel anti
      infective drug discovery.
AB  - In large part, antimicrobial drug discovery is driven by the breadth and quality
      of both potential drug targets and available chemical libraries to screen.
      Traditionally, targets have been few in number and have been limited to those
      with known function, from which biochemical assays could be implemented into drug
      screens. Iterations of this same basic approach, applied to a few biochemically
      defined targets have identified a limited set of novel antibiotics and even fewer
      antifungal agents. Indeed, in the last 50 years less than 30 antimicrobial
      targets have been exploited commercially. Within infectious disease, the industry
      was driven largely by chemistry-based approaches, simply making new analogs to
      existing drugs to overcome the growing problem of drug resistance. Elitra
      Pharmaceutical s approach has been to enable true functional genomics on a genome
      wide scale. Elitra s vision has been to identify all of the essential genes
      directly in the key pathogenic organisms. Having moved rapidly towards the
      completion of this goal, we are now faced with the enviable challenge of
      prioritizing enormous target sets and developing novel sensitive screens for
      those best suited as definitive drug targets. These highly sensitive, cell-based
      screening paradigms enable re-screening of even well screened chemical libraries
      to reveal new chemical entities displaying novel modes of action against new
      targets. In parallel, we have also begun to shift the paradigm from screening
      targets singly, towards genome-wide approaches to drug screening.

PMID- 12052226
TI  - The promise of structural genomics in the discovery of new antimicrobial agents.
AB  - Structural Genomics stands out among the emerging fields of proteomics since it
      influences the drug discovery process at so many points. Recent developments in
      protein expression technologies, x-ray crystallography and NMR spectroscopy
      provide the essential elements for high-throughput structure determination
      platforms. Bioinformatics methods to interrogate the resulting data will provide
      comprehensive, genome-wide databases of protein structure. Genomic sequencing and
      methods for high-throughput expression and protein purification are furthest
      advanced for microbial genes and so these have been the early targets for
      structural genomics initiatives. The information will be invaluable in
      understanding gene function, designing broad-spectrum small molecule inhibitors
      and in better understanding drug-host interactions.

PMID- 12052227
TI  - Protein interaction domain mapping for the selection of validated targets and
      lead compounds in the anti-infectious area.
AB  - Despite considerable progress in the analysis of microbial genomes, the number of
      validated targets suitable for the development of drugs acting on agents causing
      infectious diseases remains modest. The diversity of new chemical entities
      specific for such targets has almost not increased over the last years, while
      resistance to anti-infectious drugs has, in contrast, become a real threat in
      certain surroundings. New strategies are thus needed for selecting novel
      validated targets. We discuss here a combined approach which uses protein
      interaction mapping as the basic strategy to identify interacting domains which
      then serve to validate newly identified targets. The interactome of Helicobacter
      pylori is used as model to successively describe high-throughput protein
      interaction mapping, use of the H. pylori data to predict the interactome from
      other bacteria, analysis of interacting domains, and evaluation of the capacity
      of one such domain to block synthesis of flagella. The general applicability of
      this approach to target identification and validation, and to development of
      novel compounds is also discussed.

PMID- 12052228
TI  - Roles of the ovarian surface epithelium in ovulation and carcinogenesis.
AB  - Although ovarian mechanisms of ovulation have been a subject of investigation for
      more than a century, essential regulatory pathways remain uncertain. A role for
      the ovarian surface epithelium in ovulation has recently been demonstrated.
      Ovarian surface epithelial cells in close contact with the apical wall of
      preovulatory ovine follicles secrete a urokinase-type plasminogen activator in
      response to surge concentrations of (locally delivered) gonadotrophins. Urokinase
      activates latent collagenases and stimulates release of tumour necrosis factor
      alpha from thecal endothelium. Tumour necrosis factor alpha progressively induces
      matrix metalloproteinase gene expression, apoptosis and inflammatory necrosis.
      Collagenolysis and cellular death are a prelude to stigma formation and ovarian
      rupture. Epithelium exfoliated from the dome of ovulatory follicles is
      replenished by generative stem cell replication and migration from the wound
      edges. Common epithelial ovarian cancer has been related to successive bouts of
      ovulation and mitosis. The integrity of the DNA of surface cells circumjacent to
      the ovarian rupture site is compromised during the ovulatory process. Clonal
      expansion of an epithelial cell with damaged (unrepaired) DNA is a putative
      factor in carcinogenesis. Ovarian cancer is a deadly insidious disease because
      typically it is asymptomatic until the malignancy has reached beyond the ovaries.

PMID- 12052229
TI  - Segregation of mitochondrial DNA (mtDNA) in human oocytes and in animal models of
      mtDNA disease: clinical implications.
AB  - Mitochondrial DNA (mtDNA) is almost entirely maternally inherited. Thousands of
      copies of mtDNA are present in every nucleated cell and in most normal
      individuals these are virtually identical (homoplasmy). mtDNA diseases may be
      caused by mutations in either mitochondrial or nuclear genes and, hence, give
      rise to maternal or autosomal patterns of inheritance. Antenatal diagnosis of
      mitochondrial diseases based on chorionic villous sampling is available for
      Mendelian disorders and the syndromes caused by mutations at bp 8993 (associated
      with Leigh's syndrome and neurogenic weakness, ataxia and retinitis pigmentosa
      (NARP)). However, prenatal diagnosis of many other maternally inherited mtDNA
      diseases is less reliable because it is not possible to predict with confidence
      the way in which heteroplasmic mtDNA mutations segregate within tissues and find
      clinical expression. This review focuses on the substantial progress in genetics
      that has been made recently, and on the management options that clinicians can
      offer to families.

PMID- 12052230
TI  - Detection and location of the enzymes of de novo pyrimidine biosynthesis in
      mammalian spermatozoa.
AB  - Enzymes of the pathway for de novo biosynthesis of pyrimidine nucleotides have
      been reported in spermatozoa from fruitfly and mammals. The aim of the present
      study was to test the hypothesis that the enzymes for biosynthesis of uridine
      monophosphate (UMP) are concentrated near the mitochondria, which are segregated
      in the mid-piece of spermatozoa. Baby hamster kidney fibroblasts were compared
      with spermatozoa from rams, boars, bulls and men. Antibodies raised against
      synthetic peptides from sequences of the multienzyme polypeptides containing
      glutamine-dependent carbamyl phosphate synthetase, aspartate transcarbamylase and
      dihydroorotase (CAD) and UMP synthase, which catalyse reactions 1-3 and 5-6,
      respectively, were used, together with an affinity-purified antibody raised
      against dihydroorotate dehydrogenase (DHODH), the mitochondrial enzyme for step
      4. Western blot analysis, immunofluorescent microscopy and immunoelectron
      microscopy confirmed that CAD and UMP synthase are found in the cytoplasm around
      and outside the mitochondria; DHODH is found exclusively inside the mitochondria.
      CAD was also located in the nucleus, where it has been reported in the nuclear
      matrix, and in the cytoplasm, apparently associated with the cytoskeleton. It is
      possible that CAD in the cytoplasm has a role unconnected with pyrimidine
      biosynthesis.

PMID- 12052231
TI  - Impact of maternal nutrition during pregnancy on pituitary gonadotrophin gene
      expression and ovarian development in growth-restricted and normally grown late
      gestation sheep fetuses.
AB  - The influence of maternal nutrition during pregnancy on anterior pituitary
      gonadotrophin gene expression and ovarian development in sheep fetuses during
      late gestation was investigated. Embryos recovered from superovulated adult ewes
      that had been inseminated by a single sire were transferred, singly, into the
      uteri of adolescent recipients. After embryo transfer, adolescent ewes were
      offered a high or moderate amount of a complete diet. Pregnancies were terminated
      at day 131 +/- 0.6 of gestation and the fetal brain, anterior pituitary gland and
      gonads were collected. Gonadotrophin gene expression (LHbeta and FSHbeta
      subunits) in the fetal pituitary gland was examined using in situ hybridization.
      Ovarian follicular development was quantified in haematoxylin- and eosin-stained
      ovarian sections embedded in paraffin wax. Six dams that were offered a high
      nutrient intake carried normal-sized fetuses (weight within +/- 2 SD of mean
      weight for control fetuses from dams fed a moderate level of complete diet) and
      13 dams carried growth-restricted fetuses (weight <or= +/- 2 SD of mean weight
      for control fetuses from dams fed a moderate level of complete diet). Mean
      placental masses in these groups were 354 +/- 24.5 and 230 +/- 21.1 g,
      respectively, compared with 442 +/- 54.3 g in the dams that were offered a
      moderate nutrient intake (n = 6). Growth-restricted fetuses from dams offered a
      high nutrient intake showed higher pituitary LHbeta mRNA expression (P < 0.05)
      than normal-sized fetuses from dams offered a moderate nutrient intake (252 +/-
      21.6 and 172 +/- 23.6 nCi g(-1), respectively). FSHbeta mRNA expression was not
      influenced by growth status. Fewer follicles (primarily in the resting pool) were
      observed in the ovaries of both growth-restricted (P < 0.002) and normal-sized
      fetuses from dams offered a high nutrient intake (P < 0.01) compared with normal
      sized fetuses from dams offered a moderate nutrient intake. Irrespective of
      nutritional treatment, the total number of follicles was positively associated
      with placental mass (P < 0.01). Thus, a high maternal nutrient intake during
      adolescent pregnancy had a negative influence on ovarian follicular development
      in fetuses as determined during late gestation.

PMID- 12052232
TI  - Expression and localization of inhibin alpha, inhibin/activin betaA and betaB and
      the activin type II and inhibin beta-glycan receptors in the developing human
      testis.
AB  - Inhibins and activins have roles in the regulation of cell proliferation and
      differentiation in a variety of tissues. This study investigated the distribution
      of the three inhibin/activin subunits (alpha, betaA and betaB) and their
      receptors in the human testis between week 13 and week 19 of gestation using RT
      PCR and immunohistochemistry. mRNA for all three subunits and for the activin
      type II receptors ActRIIA and ActRIIB was detected at all stages of gestation
      examined. Sertoli cells showed intense immunostaining for the alpha subunit and
      some staining for the betaB subunit, whereas only the betaB subunit was detected
      in gonocytes. No betaA subunit staining was detected within the tubules. All
      three subunits were localized to interstitial Leydig cells. Cells of the rete
      testis and the epididymal epithelium also showed immunostaining for betaB;
      however, staining for the other subunits was weak or absent. Peritubular cells
      showed intense immunostaining for the beta-glycan inhibin receptor, which was
      also localized to interstitial cells, but was not detected within the tubular
      compartment, rete testis or epididymal epithelium. ActRIIA was detected in
      gonocytes and in interstitial cells; ActRIIB was distributed widely. These data
      indicate that fetal Leydig and Sertoli cells have the potential to produce both
      activins and inhibins, whereas gonocytes may produce only activin B. The
      distribution of activin and inhibin receptors implies that the intratubular
      compartment and developing duct system are sites of action of activin B but not
      inhibin at this stage of development, whereas both activins and inhibins may be
      involved in the development and function of the peritubular and interstitial
      cells.

PMID- 12052233
TI  - Insulin-like growth factor (IGF) system in the oocyte and somatic cells of bovine
      preantral follicles.
AB  - Many studies have highlighted the role of the insulin-like growth factor (IGF)
      system in the control of antral follicular growth. However, much less is known
      about the involvement of the IGF system in the regulation of preantral follicular
      development. In an attempt to address this lack of knowledge, the present study
      describes the spatial and temporal patterns of expression of mRNA encoding
      components of the IGF system in bovine follicles during preantral stages of
      development. mRNA was detected by in situ hybridization using frozen sections (14
      microm) of bovine ovarian tissue. Serial sections were probed with 35S-labelled
      bovine riboprobes. Type 1 IGF receptor mRNA was detected in granulosa cells and
      in the oocyte of preantral follicles; however, in this study, as in previous
      studies, it was not possible to detect mRNA encoding either IGF-I or -II. IGF
      binding protein (IGFBP)-2 mRNA was present in granulosa cells and oocytes of
      preantral follicles, and immunoreactive IGFBP-2 was detected around granulosa
      cells during this early stage of development. Occasionally, preantral follicles
      were identified in which there was no expression of IGFBP-2 in granulosa cells or
      the oocyte. IGFBP-3 mRNA was detected in the oocyte of preantral follicles and in
      the surrounding stromal tissue. mRNAs encoding IGFBP-2 and -3, and type 1 IGF
      receptor were first detected in type 2 follicles. In conclusion, although the IGF
      ligands are not expressed in preantral follicles, mRNAs encoding the type 1 IGF
      receptor, and IGFBP-2 and -3 were present and showed unique spatial patterns of
      expression within preantral follicles.

PMID- 12052234
TI  - Roles of gene transcription and PKA subtype activation in maturation of murine
      oocytes.
AB  - The aims of this study were to examine the role of transcription and the
      coincident involvement of type I and type II protein kinase A (PKA) in the
      resumption of meiosis in murine cumulus-oocyte complexes (COCs) using the
      transcriptional inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB)
      and alpha-amanitin. The first series of experiments was designed to: (i)
      characterize the role of transcription in gonadotrophin-mediated and spontaneous
      maturation of murine oocytes; (ii) examine the roles of specific gonadotrophins
      (FSH versus hCG) and cumulus cells in transcriptionally mediated oocyte
      maturation; and (iii) determine the reversibility of the transcriptional arrest
      of meiosis. In the presence of FSH, transcriptional inhibitors arrested germinal
      vesicle breakdown (GVBD) (DRB: 2 +/- 2% and control: 76 +/- 2%; alpha-amanitin: 4
      +/- 4% and control: 70 +/- 4%). Furthermore, cumulus cells were required for
      transcriptional inhibitors to arrest GVBD (DRB with cumulus cells: 0 +/- 15%; DRB
      without cumulus cells: 94 +/- 13%; alpha-amanitin with cumulus cells: 15 +/- 2%;
      alpha-amanitin without cumulus cells: 99 +/- 2%). Thus, in mice, FSH-mediated
      GVBD uses a transcriptional mechanism, which probably occurs within the cumulus
      cell compartment. In a second series of experiments, the role of transcription in
      mediating the resumption of meiosis after activation of either type I or type II
      PKA was examined. Activation of type I PKA in murine COCs resulted in an arrest
      of GVBD that was independent of a transcriptional event (with DRB: 7 +/- 9% GVBD;
      without DRB: 11 +/- 9% GVBD). In contrast, activation of type II PKA resulted in
      a resumption of meiosis, which required the occurrence of gene transcription
      (with DRB: 12 +/- 9% GVBD; without DRB: 80 +/- 9% GVBD). As FSH binding to
      cumulus cells activates the PKA second messenger system, our results indicate
      that, in cultured murine COCs, FSH binding to cumulus cells results in the
      activation of type II PKA, which, in turn, mediates a downstream transcriptional
      event required for the initiation of GVBD.

PMID- 12052235
TI  - In vitro development of pig preantral follicles cultured in a serum-free medium
      and the effect of angiotensin II.
AB  - A novel culture system is reported in which pig preantral follicles (< 300 microm
      in diameter) with an intact thecal cell layer were isolated and cultured in a
      serum-free medium for up to 30 days. The medium supported follicle culture after
      isolation, while maintaining both somatic cell and oocyte viability. Follicles
      were cultured in groups (n = 3 per group) on collagen-coated wells for 16 days,
      during which they retained a three-dimensional structure, maintained oocyte
      viability and increased in diameter and number of somatic cells. Follicle culture
      for 30 days resulted in a further increase in number of cells, oocyte viability
      was maintained, and a significant increase in follicle diameter was observed (P <
      0.001), with 29% of follicles forming an antrum. Follicles synthesized measurable
      quantities of progesterone (168 pg per 100 microl per 48 h; no significant
      increase with time) and increasing quantities of oestradiol (136 pg per 100
      microl per 48 h; P < 0.001 with time). Further supplementation of the medium with
      100 micromol testosterone l(-1) at day 28 resulted in a significant increase in
      oestradiol secretion by both antral (P < 0.01) and preantral follicles (P <
      0.05). Culture over 30 days in medium with 10(-10) mol angiotensin II l(-1) and
      further supplementation at day 28 with 100 micromol testosterone l-1 also
      increased oestradiol synthesis (P < 0.001). These results show that viable
      preantral follicles may be cultured for extended periods, and indicate that the
      possible role of angiotensin II in folliculogenesis and steroidogenesis in early
      development of pig follicles requires further investigation.

PMID- 12052236
TI  - Differences in splicing of mRNA encoding LH receptor in theca cells according to
      breeding season in ewes.
AB  - Splice variants of mRNA encoding the LH receptor (LHR) during follicular
      development were characterized in cyclic and non-cyclic ewes. Granulosa and theca
      cells were collected from individual follicles. After amplification by RT-PCR of
      a region situated between exon 9 and exon 11 of the LHR gene, three distinct
      bands, LHR1 (full length), LHR2 (deletion of exon 10), LHR3 (deletion of 262 bp
      in exon 11), were observed in the granulosa and theca cells of ovine antral
      follicles of various sizes (2.5-6.0 mm). Expression of LHR mRNA in theca cells
      varied with the annual cycle of reproduction (P < 0.001), and was highly
      expressed in all classes of follicle collected from anoestrous ewes (1.3 +/- 0.1,
      n = 8 in small follicles; 1.8 +/- 0.2, n = 8 in medium follicles; 1.7 +/- 0.3, n
      = 4 in large follicles; arbitrary units) compared with follicles collected from
      oestrous ewes (0.19 +/- 0.06, n = 8 in small follicles; 0.2 +/- 0.04, n = 9 in
      medium follicles; 0.18 +/- 0.04, n = 5 in large follicles). During the breeding
      season, no differences in the relative expression of the different splice
      variants were observed according to follicle size. In contrast, during anoestrus,
      LHR3 mRNA was significantly more abundant in large (6.0-6.5 mm) and medium (4.0
      5.5 mm) than it was in small (2.5-3.5 mm) follicles. These results indicate that
      RNA alternative splicing plays a role in the seasonal and physiological control
      of LH receptor expression in theca cells.

PMID- 12052237
TI  - Production of inhibin A not B in rams: changes in plasma inhibin A during testis
      growth, and expression of inhibin/activin subunit mRNA and protein in adult
      testis.
AB  - Previous studies have shown that changes in the plasma concentrations of
      immunoreactive inhibin measured by radioimmunoassay occur in parallel with growth
      and regression of the testes during a reproductive cycle in adult Soay rams
      induced by exposure to an artificial lighting regimen of alternating 16 week
      periods of long days and short days. With the development of new two-site ELISAs
      for sheep inhibin A and inhibin B, we have re-examined the relationship between
      FSH and dimeric, biologically active inhibin in the reproductive cycle in adult
      Soay rams. No signal was generated by sheep testicular extract, ram or ewe
      plasma, or sheep ovarian follicular fluid in the inhibin B ELISA. In contrast,
      ram plasma contained significant activity in the inhibin A ELISA, which diluted
      in parallel to the inhibin A standard, and was abolished by preincubation of ram
      plasma with monoclonal antibodies specific for the betaA, but not the betaB,
      subunit. These results indicate that the ram is the first adult male mammalian
      species identified to date in which the testes produce and secrete dimeric
      inhibin A and not inhibin B. Northern blot analysis and immunocytochemistry
      confirmed the presence of alpha, betaA and betaB inhibin/activin subunit mRNA and
      protein in the testes of adult rams. Changes in plasma inhibin A concentrations
      occurred in parallel with the growth and regression of the testes during the long
      day: short day: long day lighting regimen in adult Soay rams, confirming our
      previous observations with immunoreactive inhibin. During the growth phase of the
      testes in the first 8 weeks of exposure to short days there was a positive
      correlation between plasma FSH and inhibin A concentrations, indicating that
      during this phase the secretion of inhibin A is stimulated by FSH and that
      inhibin A did not act as a negative feedback hormone on FSH secretion. From week
      8.5 to week 16.0 of exposure to short days, there was a negative correlation
      between FSH and testosterone concentrations, but not inhibin, indicating that
      when inhibin concentrations are high, testosterone acts as the negative regulator
      of FSH secretion. Thus, in intact adult rams, when the testes are fully active it
      appears that inhibin A may sensitize the pituitary to the negative feedback
      effects of testosterone, at which time they act synergistically to maintain
      plasma concentrations of FSH.

PMID- 12052238
TI  - Influence of uterine bacterial contamination after parturition on ovarian
      dominant follicle selection and follicle growth and function in cattle.
AB  - First postpartum dominant follicles are preferentially selected in the ovary
      contralateral to the previously gravid uterine horn. The aim of the present study
      was to test the hypothesis that uterine bacterial contamination alters the
      location of ovarian follicle emergence and selection, and inhibits follicle
      growth and function. Swabs were collected from the uterine body lumen of cattle
      on days 7, 14, 21 and 28 after parturition. Bacteria were identified by aerobic
      and anaerobic culture; bacterial growth was scored semiquantitatively and animals
      were categorized into standard or high bacterial contamination categories on the
      basis of the number of colonies detected. Follicular growth and function were
      monitored by daily transrectal ultrasonography, and estimation of plasma FSH,
      oestradiol and progesterone concentrations. There was no effect of bacterial
      contamination on plasma FSH concentration profiles or emergence of the ovarian
      follicle wave. When uterine bacterial growth scores were high on day 7 or day 21
      after parturition, fewer first (1/20 versus 15/50; P < 0.05) or second (1/11
      versus 13/32; P < 0.05) dominant follicles were selected in the ipsilateral
      compared with the contralateral ovary, respectively. The diameter of the first
      dominant follicle was smaller in animals with a high day 7 bacterial score (P <
      0.001), dominant follicle growth was slower (P < 0.05) and oestradiol secretion
      was decreased (P < 0.05). The present study provides evidence for an effect of
      the uterus on the ovary after parturition, whereby uterine bacteria have a
      contemporaneous localized effect on ovarian follicle selection and subsequent
      growth and function, but not on initial emergence.

PMID- 12052239
TI  - Evaluation of the immunocontraceptive potential of Escherichia coli-expressed
      recombinant dog ZP2 and ZP3 in a homologous animal model.
AB  - Dog zona pellucida glycoprotein 2 (dZP2), excluding the N-terminal signal
      sequence and the C-terminal transmembrane-like domain, was cloned and expressed
      as a polyhistidine fusion protein in Escherichia coli to evaluate the
      immunocontraceptive efficacy of ZP glycoproteins. The recombinant dZP2 (rec-dZP2)
      revealed a 70 kDa band corresponding to the full length transcript, as well as
      several low molecular mass fragments in western blot analysis. In addition to rec
      dZP2, E. coli expressed recombinant dog ZP glycoprotein 3 (rec-dZP3), which has
      also been evaluated for its efficacy to block fertility in a homologous system.
      Three groups of female dogs (n = 4 per group) were immunized with rec-dZP2
      conjugated to diphtheria toxoid (rec-dZP2-DT), rec-dZP3 conjugated to DT (rec
      dZP3-DT) and DT alone. Immunization of female dogs with rec-dZP2-DT and rec-dZP3
      DT led to generation of antibodies against the respective ZP proteins as well as
      to DT. Subsequent to mating, the four female dogs immunized with rec-dZP2-DT all
      conceived, which is indicative of failure of the anti-rec-dZP2 antibodies to
      block fertility. In the group of dogs immunized with rec-dZP3-DT, three of four
      animals did not conceive when mated with males of proven fertility. The block in
      fertility was associated with anti-dZP3 antibody titres. Ovarian histopathology
      revealed that the block in fertility in the group immunized with rec-dZP3-DT is
      probably manifested by inhibition in the development of follicles and is due to
      atretic changes in the zona pellucida. These results, although preliminary,
      indicate that immunization with dZP3 may be a feasible proposition to control dog
      populations provided that adequate antibody titres are achieved.

PMID- 12052240
TI  - Expression of the insulin-like growth factor (IGF) system in the bovine oviduct
      at oestrus and during early pregnancy.
AB  - Early mammalian embryo development in vitro can be enhanced by co-culture with
      oviductal cells and by the addition of insulin-like growth factors (IGFs). This
      study examined the expression patterns of the oviductal IGF system in cattle in
      relation to the number of days after oestrus and the presence or absence of
      embryos. Oviducts were collected from: (i) 66 nulliparous heifers on day 3, day 6
      or day 16 after insemination and from (ii) ten non-pregnant, lactating cows on
      day 0 or day 1 of the oestrous cycle. Oviducts were coiled, frozen whole and
      sectioned for in situ hybridization. Expression patterns of mRNAs encoding IGF-I,
      IGF-II, type 1 IGF receptor (IGF-1R), and the IFG binding proteins (IGFBP)-1, -3
      and -5 were determined from autoradiographs. Separate measurements were made for
      the mucosa and muscle layers of the infundibulum, ampulla and isthmus. None of
      the parameters measured differed between heifers with or without the presence of
      an embryo. mRNAs encoding IGF-I and IGF-1R were present in the mucosa and muscle
      of all three oviductal regions, and the highest value of IGF-I mRNA was measured
      in heifers on day 3. IGF-II mRNA was expressed predominantly in the muscle wall.
      IGFBP-1 mRNA was not detectable, whereas mRNAs encoding IGFBP-3 and -5 were
      expressed in both the muscle and mucosa. IGFBP-3 expression was higher in cows on
      day 0 and day 1 of the oestrous cycle than in heifers on day 3, day 6 and day 16
      after insemination. A peak of IGFBP-5 expression was reached on day 6. Locally or
      systemically produced IGFs, regulated by IGFBPs, may act directly on the embryo
      or indirectly via modulation of oviductal secretions and muscular activity to
      influence the success of early embryo development.

PMID- 12052241
TI  - Prediction of fertility by centrifugal countercurrent distribution (CCCD)
      analysis: correlation between viability and heterogeneity of ram semen and field
      fertility.
AB  - The prediction of the fertilizing ability of a sire or a given insemination dose
      is a primary aim in the field of artificial insemination. Centrifugal
      countercurrent distribution analysis (CCCD) was used to determine the
      relationship between some sperm parameters and the in vivo fertility rate
      obtained with the same sample after cervical artificial insemination. A total of
      522 ewes from 26 different farms was inseminated with 53 ejaculates obtained from
      25 mature Rasa aragonesa rams. Semen was diluted to 1.6 x 10(9) cells ml-1 and
      doses of 0.25 ml were prepared and kept at 15 degrees C until used for
      insemination. The same ejaculates were used for analysis of standard semen
      parameters and CCCD analysis. Sperm motility, concentration and viability were
      determined before and after CCCD. Post-CCCD parameters were derived from the
      analysis of the profile obtained after CCCD. The recovered viability showed the
      highest correlation with fertility, especially in the central chambers (V2), r =
      0.415, P < 0.005). The ejaculate heterogeneity also showed a positive correlation
      with field fertility (r = 0.23), with a tendency towards significance (P < 0.1).
      The mean fertility value of all ejaculates used in this study was 46.75%, ranging
      from 12.5% to 75.0%. Ejaculates were classified into two categories according to
      their fertility: higher and lower than the mean value. Only the viability
      recovered in the central chambers (V2) was a parameter with a predictive capacity
      to discriminate between the two groups (P < 0.05). A predictive equation for
      field fertility with a correlation coefficient r = 0.488 and a very high level of
      significance (P < 0.005) was deduced by multiple analysis: PF = 6.02 + 0.069V2 +
      0.315H (where PF is predictive fertility, V2 is the recovered viability in the
      CCCD profile central chambers and H is heterogeneity).

PMID- 12052242
TI  - Non-invasive assessment of oestrous cycles and evaluation of reproductive
      seasonality in the female wild black rhinoceros (Diceros bicornis minor).
AB  - Female wild black rhinoceroses in Zimbabwe were monitored non-invasively using
      faecal progesterone metabolite analysis and observation of reproductive
      behaviour. A postpartum period of reproductive inactivity of at least 4 months,
      followed by a period of 4-7 months of oestrous cyclicity, was detected in six
      multiparous females. Three-quarters of the oestrous cycles (n = 21) had a total
      duration (mean +/- SEM) of 26.8 +/- 1 days. Other types of cycle were
      characterized either by an extended luteal phase, lasting on average twice as
      long as the normal cycle, or by an extended follicular phase. These extended
      cycles may have resulted from early embryo loss and heat stress. Female
      rhinoceroses did not conceive before 8 months after giving birth and some females
      (n = 2) most likely aborted after 3.0-3.5 months of gestation. The detected
      period of cyclic oestrus occurred between May and March in females (n = 9), and
      there was a 3 month extended interoestrous interval in nulliparous females during
      the period of decreasing daylengths that can be presumed to be the period of
      poorest fertility for the black rhinoceros under tropical latitudes. In contrast,
      the period of optimum fertility in the Southern hemisphere coincided with the
      late spring and early summer, and corresponded to the early rainy season. As a
      result, a higher incidence of births was detected in the late rainy season,
      providing the lactating female with the most suitable environment in terms of
      nutritional requirements.

PMID- 12052243
TI  - Effects of leptin administration and feed restriction on thecal leucocytes in the
      preovulatory rat ovary and the effects of leptin on meiotic maturation, granulosa
      cell proliferation, steroid hormone and PGE2 release in cultured rat ovarian
      follicles.
AB  - Leptin is expressed by adipocytes and is thought to play a role in regulating
      food intake and in reproduction. It has been demonstrated that acute leptin
      administration to immature gonadotrophin-primed rats in vivo inhibits ovulation
      and causes a decline in food intake. However, feed restriction alone does not
      inhibit ovulation. Two experiments were designed to investigate the mechanism of
      leptin-induced inhibition of ovulation. In the first experiment, which was
      prompted by the importance of ovarian leucocytes in ovulation, the role of
      leucocytes in leptin-induced inhibition of ovulation was investigated. The second
      experiment investigated whether high leptin concentrations could inhibit other
      factors important to ovulation, such as meiotic competence of oocytes, granulosa
      cell proliferation, steroid or PGE(2) release, and interleukin 1beta production,
      in vitro. In the first experiment, the populations of neutrophils and monocytes
      macrophages in the preovulatory follicles of gonadotrophin-primed, leptin-treated
      and -untreated rats were examined. A decrease in food intake, as a result of
      either leptin treatment or feed restriction, specifically reduced the numbers of
      neutrophils and monocytes-macrophages infiltrating the theca interna of
      preovulatory follicles without affecting the numbers found in the stroma. The
      findings show that reduced infiltration of thecal neutrophils and macrophages
      into preovulatory follicles is a response to reduced food intake. Furthermore,
      this reduction is not the direct cause of the leptin-induced inhibition of
      ovulation. In the second experiment, ovarian follicles were cultured for 4 or 12
      h in the presence or absence of the following hormones: FSH (500 miu), insulin
      like growth factor I (IGF-I) (50 ng ml(-1)), LH (100 ng ml(-1)) and leptin (300
      ng ml(-1)). The results demonstrated that high concentrations of leptin in
      follicle culture do not affect meiotic maturation or steroid release, but tend to
      inhibit release of PGE 2 (although this result was not significant). DNA
      synthesis in granulosa cells was not inhibited by leptin in FSH- and IGF-I
      supplemented culture media. These results are in agreement with previous studies
      that have shown that leptin inhibits the stimulatory effects of IGF-I on FSH
      stimulated oestradiol production in rat granulosa cells without affecting
      progesterone production. In summary, leptin does not appear to have an adverse
      effect on the components of ovulation tested in this study, and therefore must
      impact on the ovulatory cascade in a way that remains to be defined.

PMID- 12052244
TI  - Expression of the long (OB-RB) and short (OB-RA) forms of the leptin receptor
      throughout the oestrous cycle in the mature rat ovary.
AB  - Leptin is secreted by adipocytes and exerts its effects by interacting with the
      long form of the leptin receptor, OB-RB. The leptin protein and leptin receptors
      have been localized in the ovary, and acute leptin treatment directly inhibits
      ovulation in the rat ovary. It was hypothesized that expression of the leptin
      receptor gene varies throughout the oestrous cycle to modulate the sensitivity of
      the ovary to leptin. In this study, expression of genes for the long and short
      isoforms of the leptin receptor in the adult ovary was investigated at different
      stages of the rat oestrous cycle. Vaginal cytology was used to determine the
      stage of the oestrous cycle. Ovaries were collected and RNA was extracted for
      real-time RT-PCR analysis of leptin receptor gene expression. OB-RB gene
      expression was low in pro-oestrus (3.13 +/- 0.18 fg RNA per microg total DNA) and
      dioestrus II (2.52 +/- 0.19 fg RNA per microg total DNA) of the oestrous cycle,
      whereas expression was high in oestrus (5.9 +/- 0.27 fg RNA per microg total DNA)
      and dioestrus I (4.6 +/- 0.24 fg RNA per microg total DNA) (P < 0.001).
      Expression of the gene for the short form of the leptin receptor (OB-RA) was at a
      maximum in dioestrus I (65.5 +/- 0.8 fg RNA per ng total DNA), high in oestrus
      (39.0 +/- 0.8 fg RNA per ng total DNA) and low at pro-oestrus (5.0 +/- 0.2 fg RNA
      per ng total DNA) and dioestrus II (1.1 +/- 0.09 fg RNA per ng total DNA) (P <
      0.001). Plasma oestradiol concentrations (pg ml-1) were highest at pro-oestrus
      (19.38 +/- 1.3), and similar at the remaining three stages studied (oestrus: 13.7
      +/- 1.9; dioestrus I: 12.4 +/- 1.0; dioestrus II: 10.3 +/- 0.9) (P < 0.05).
      Plasma progesterone concentrations (ng ml-1) were higher in the luteal phases of
      the oestrous cycle (dioestrus I: 18.6 +/- 2.3; dioestrus II: 14.7 +/- 2.5) than
      during pro-oestrus (5.12 +/- 0.6) and oestrus (5.9 +/- 0.8) (P < 0.05). Plasma
      leptin concentrations were detectable only in pro-oestrus (0.35 +/- 0.05 ng ml(
      1)) and were below the detection limit of the assay at other stages of the
      oestrous cycle. In summary, mRNA content for the long and short isoforms of the
      leptin receptor is lower in pro-oestrus and dioestrus II than in oestrus and
      dioestrus I of the rat oestrous cycle. The fluctuations in leptin receptor mRNA
      content may be a response to the concentrations of circulating steroid hormones
      and leptin. This research supports the initial hypothesis and shows that ovarian
      leptin receptor concentrations vary throughout the oestrous cycle in response to
      the changing environment of the ovary.

PMID- 12052245
TI  - Effect of dextrans on cryopreservation of goat cauda epididymal spermatozoa using
      a chemically defined medium.
AB  - Experiments were carried out to investigate the cryoprotecting potential of
      dextrans (ranging from 10 to 2000 kDa) using a synthetic model system developed
      recently in this laboratory. Goat spermatozoa from the cauda epididymidis were
      extracted in a chemically defined medium (modified Ringer's solution) and assayed
      for motility using a phase-contrast microscope. The sperm cells were subjected to
      a freezing protocol in a computer-controlled biofreezer (cooling at 0.25 degrees
      C min(-1) to 5 degrees C; 5 degrees C min(-1) to -20 degrees C; 20 degrees C min(
      1) to -100 degrees C) and plunged into liquid nitrogen. The frozen cells were
      thawed rapidly at 37 degrees C in a thermostatic waterbath. In the absence of
      dextran, all the spermatozoa lost their motility. The cryoprotecting efficacy of
      each dextran was found to be biphasic in nature. Initially, as the concentration
      of dextran was increased, the recovery of sperm motility also increased and
      reached an optimum value; however, with further increases in dextran
      concentration, the recovery of motility decreased sharply. Of all the sugar
      polymers tested, 10 kDa dextran showed the highest cryoprotecting efficacy,
      whereas the 2000 kDa sugar polymer was the least active. Dextrans of 10, 40, 73,
      173, 252, 500 and 2000 kDa offered maximum cryorecovery of forward motility to
      the extent of approximately 23%, 21%, 19%, 18%, 16%, 15% and 8%, respectively.
      Optimum concentrations of these dextrans for cryoprotection of sperm motility
      were 8.42, 2.50, 1.09, 0.37, 0.31, 0.10 and 0.04 mmol l(-1), respectively. It
      thus appears that each dextran has a characteristic cryoprotection profile. The
      data show that the cryoprotecting efficacy and optimum cryoprotecting
      concentrations of dextrans are inversely related to their molecular mass. Dextran
      also served as a significant cryoprotectant in the presence of glycerol (0.87 mol
      l(-1)) and dimethyl sulphoxide (0.76 mol l(-1)), which are well known
      cryoprotectants; the action of the combined cryoprotectants was almost additive.
      The presence of glycerol or glycerol plus dimethyl sulphoxide caused a
      significant reduction (from 8.42 to 6.27 mmol l(-1)) in the optimum concentration
      of dextran. In the presence of the three cryoprotectants, recovery of sperm
      motility was as high as 58% (forward motility) and 60% (total motility).

PMID- 12052246
TI  - Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro
      acting at different stages with positive cooperativity. Application of micro
      array analysis.
AB  - BACKGROUND: Dimethyl sulfoxide (DMSO) is frequently used at a concentration of up
      to 95% in the formulation of antiherpetic agents because of its properties as a
      skin penetration enhancer. Here, we have analyzed the effect of DMSO on several
      parameters of Herpes Simplex Virus replication. METHODS: Productive infection
      levels of HSV-1 were determined by plaque assay or by reporter gene activity, and
      its DNA replication was estimated by PCR. Transcript levels were evaluated with
      HSV-specific DNA micro-arrays. RESULTS: DMSO blocks productive infection in vitro
      in different cell types with a 50% inhibitory concentration (IC50) from 0.7 to 2%
      depending upon the multiplicity of infection. The concentration dependence
      exhibits a Hill coefficient greater than 1, indicating that DMSO blocks
      productive infection by acting at multiple different points (mechanisms of
      action) with positive cooperativity. Consistently, we identified at least three
      distinct temporal target mechanisms for inhibition of virus growth by DMSO. At
      late stages of infection, DMSO reduces virion infectivity, and markedly inhibits
      viral DNA replication. A third mode of action was revealed using an
      oligonucleotide-based DNA microarray system for HSV. These experiments showed
      that DMSO reduced the transcript levels of many HSV-1 genes; including several
      genes coding for proteins involved in forming and assembling the virion. Also,
      DMSO markedly inhibited some but not all early transcripts indicating a
      previously unknown mode for inhibiting the early phase of HSV transcription
      replication cycle. CONCLUSION: These observations suggest that DMSO itself may
      have a role in the anti-herpetic activity of formulations utilizing it as a
      dispersant.

PMID- 12052247
TI  - Apolipoprotein C3 SstI polymorphism and triglyceride levels in Asian Indians.
AB  - BACKGROUND: A close association between Sst I polymorphism in the 3' untranslated
      region of the apolipoproteinC3 (APOC3) gene and levels of plasma triglycerides
      (TG) had been reported by different investigators. Hypertriglyceridemia(HTG) is a
      known risk factor for coronary artery disease (CAD) in the context of Asian
      Indians. We conducted a study on the relationship between APOC3 SstI polymorphism
      (S1S1, S1S2 and S2S2 genotypes) and plasma TG levels in a group of 139 male
      healthy volunteers from Northern India. METHODS: DNA samples were analyzed by
      polymerase chain reaction (PCR) followed by SstI digestion. Digested PCR products
      were run on 3% agarose gel and visualized by ethidium bromide staining. RESULTS:
      Rare S2 allele was highly prevalent in our study population (0.313) as compared
      to the Caucasians (0.00-0.11). The genotypic distribution was in agreement with
      Hardy-Weinberg equilibrium. S2 allele was almost two times more prevalent in the
      HTG group (N = 34) as compared to NTG group (N = 105) (p = 0.001). Multiple
      logistic regression revealed S1S2 individuals had age-adjusted odds ratio of 2.43
      (95%CI = 0.99-6.01, p = 0.054) and S2S2 had 9.9 (95%CI = 2.66-37.29, p = 0.0006)
      for developing HTG in comparison to S1S1 genotype. CONCLUSIONS: Our study shows a
      significant association between rare S2 allele and HTG in Asian Indians.

PMID- 12052248
TI  - Release of annexin V-binding membrane microparticles from cultured human
      umbilical vein endothelial cells after treatment with camptothecin.
AB  - BACKGROUND: Elevated plasma counts of endothelial microparticles (MP) have been
      demonstrated in various diseases with a vascular injury component. We used flow
      cytometry to study the MP-release from cultured human umbilical vein endothelial
      cells (HUVEC) stimulated by various agonists. MP-release by a topoisomerase I
      inhibitor camptothecin has been studied in detail. RESULTS: Overnight stimulation
      of HUVEC with either LPS or TNFalpha, or 30 min stimulation with thrombin,
      phorbol-myristate-acetate, tissue plasminogen activator, or angiotensin-II did
      not cause a significant release of annexin V-binding MP. In contrast, induction
      of apoptosis with 5 microM camptothecin, documented by 60-70% desquamation of
      HUVEC culture, annexin V-binding to the cells and DNA-fragmentation, led to a
      release of annexin V-binding microparticles (approximately 80,000 MP/103 cells).
      This microparticle-release was prevented by Z-Val-Ala-Asp-fluoromethyl-ketone
      (ZVAD). Lower concentration of camptothecin (500 nM) induced comparable
      microparticle-release without loss of the culture confluence and without increase
      in annexin V-binding to the cells or DNA-fragmentation. Analyzed microparticles
      were free of nucleic acids and 95% of microparticles were 0.3-1 microm in size.
      Double-labeling flow cytometry assay showed that all annexin V-binding
      Microparticles expressed CD59 but only approximately 50% of these also expressed
      CD105. CONCLUSIONS: Camptothecin treated HUVEC released different populations of
      annexin V-binding membrane microparticles at early stage after proapoptotic
      stimulation before detection of phosphatidylserine exposure on the cells or DNA
      fragmentation. The microparticle-release was ZVAD sensitive but was not enhanced
      at the executive phase of apoptosis. These observations offer a new insight into
      microparticle-release as a marker of endothelial stimulation and injury.

PMID- 12052249
TI  - The contribution of inherited genotype to breast cancer.
AB  - The etiology of breast cancer is complex, and is likely to involve the actions of
      genes at multiple levels along the multistage carcinogenesis process. These
      inherited genotypes include those that affect the propensity to be exposed to
      breast carcinogens, and those associated with breast tumorigenesis directly. In
      addition, inherited genotypes may influence response to breast cancer
      chemoprevention and treatment. Studies relating inherited genotypes with breast
      cancer incidence and mortality should consider a broader spectrum of genes and
      their potential roles in multistage carcinogenesis than have been typically
      evaluated to date. Understanding the role of inherited genotype at different
      stages of carcinogenesis could improve our understanding of cancer biology, may
      identify specific exposures or events that correlate with carcinogenesis, or
      target relevant biochemical pathways for the development of preventive or
      therapeutic interventions.

PMID- 12052250
TI  - Hormonal control of p53 and chemoprevention.
AB  - Improvements in the detection and treatment of breast cancer have dramatically
      altered its clinical course and outcome. However, prevention of breast cancer
      remains an elusive goal. Parity, age of menarche, and age at menopause are major
      risk factors drawing attention to the important role of the endocrine system in
      determining the risk of breast cancer, while heritable breast cancer
      susceptibility syndromes have implicated tumor suppressor genes as important
      targets. Recent work demonstrating hormonal modulation of the p53 tumor
      suppressor pathway draws together these established determinants of risk to
      provide a model of developmental susceptibility to breast cancer. In this model,
      the mammary epithelium is rendered susceptible due to impaired p53 activity
      during specific periods of mammary gland development, but specific endocrine
      stimuli serve to activate p53 function and to mitigate this risk. The results
      focus attention on p53 as a molecular target for therapies to reduce the risk of
      breast cancer.

PMID- 12052251
TI  - Liposome-based drug delivery in breast cancer treatment.
AB  - Drug delivery systems can in principle provide enhanced efficacy and/or reduced
      toxicity for anticancer agents. Long circulating macromolecular carriers such as
      liposomes can exploit the 'enhanced permeability and retention' effect for
      preferential extravasation from tumor vessels. Liposomal anthracyclines have
      achieved highly efficient drug encapsulation, resulting in significant anticancer
      activity with reduced cardiotoxicity, and include versions with greatly prolonged
      circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin.
      Pegylated liposomal doxorubucin has shown substantial efficacy in breast cancer
      treatment both as monotherapy and in combination with other chemotherapeutics.
      Additional liposome constructs are being developed for the delivery of other
      drugs. The next generation of delivery systems will include true molecular
      targeting; immunoliposomes and other ligand-directed constructs represent an
      integration of biological components capable of tumor recognition with delivery
      technologies.

PMID- 12052252
TI  - Knockout and transgenic mice of Trp53: what have we learned about p53 in breast
      cancer?
AB  - The human p53 tumor suppressor gene TP53 is mutated at a high frequency in
      sporadic breast cancer, and Li-Fraumeni syndrome patients who carry germline
      mutations in one TP53 allele have a high incidence of breast cancer. In the 10
      years since the first knockout of the mouse p53 tumor suppressor gene (designated
      Trp53) was published, much has been learned about the contribution of p53 to
      biology and tumor suppression in the breast through the use of p53 transgenic and
      knockout mice. The original mice deficient in p53 showed no mammary gland
      phenotype. However, studies using BALB/c-Trp53-deficient mice have demonstrated a
      delayed involution phenotype and a mammary tumor phenotype. Together with other
      studies of mutant p53 transgenes and p53 bitransgenics, a greater understanding
      has been gained of the role of p53 in involution, of the regulation of p53
      activity by hormones, of the effect of mouse strain and modifier genes on tumor
      phenotype, and of the cooperation between p53 and other oncogenic pathways,
      chemical carcinogens and hormonal stimulation in mammary tumorigenesis. Both p53
      transgenic and knockout mice are important in vivo tools for understanding breast
      cancer, and are yet to be exploited for developing therapeutic strategies in
      breast cancer.

PMID- 12052253
TI  - CCAAT/enhancer binding proteins in normal mammary development and breast cancer.
AB  - CCAAT/enhancer binding proteins (C/EBPs) are a family of leucine zipper,
      transcription factors that bind to DNA as homodimers and heterodimers. They
      regulate cellular proliferation, differentiation and apoptosis in the mammary
      gland. Multiple protein isoforms, including truncated, dominant negatives, are
      generated by translation of the C/EBPbeta transcript or via proteolytic cleavage
      of the full-length C/EBPbeta protein. Gene deletion of individual C/EBP family
      members has demonstrated an essential role for C/EBPbeta in normal mammary
      development, while transgenic and overexpression studies provide evidence that
      the dominant-negative C/EBPbeta-liver-enriched inhibitory protein isoform induces
      proliferation in mammary epithelial cells. Mounting evidence suggests that
      alterations in the ratio of the C/EBPbeta-liver-enriched inhibitory protein
      isoform and the C/EBPbeta-liver-enriched activating protein isoform may play a
      role in the development of breast cancer. This review will consequently focus on
      C/EBP actions in normal mammary development and on the emerging data that
      supports a role in breast cancer.

PMID- 12052255
TI  - Gene expression profiles derived from fine needle aspiration correlate with
      response to systemic chemotherapy in breast cancer.
AB  - BACKGROUND: Drug resistance in breast cancer is a major obstacle to successful
      chemotherapy. In this study we used cDNA microarray technology to examine gene
      expression profiles obtained from fine needle aspiration (FNA) of primary breast
      tumors before and after systemic chemotherapy. Our goal was to determine the
      feasibility of obtaining representative expression array profiles from limited
      amounts of tissue and to identify those expression profiles that correlate with
      treatment response. METHODS: Repeat presurgical FNA samples were taken from six
      patients who were to undergo primary surgical treatment. Additionally, a group of
      10 patients who were to receive neoadjuvant chemotherapy underwent two FNAs
      before chemotherapy (adriamycin 60 mg/m2 and cyclophosphamide 600 mg/m2) followed
      by another FNA on day 21 after the first cycle. Total RNA was amplified with T7
      Eberwine's procedure and labeled cDNA was hybridized onto a 7600-feature glass
      cDNA microarray. RESULTS: We identified candidate gene expression profiles that
      might distinguish tumors with complete response to chemotherapy from tumors that
      do not respond, and found that the number of genes that change after one cycle of
      chemotherapy was 10 times greater in the responding group than in the non
      responding group. CONCLUSION: This study supports the suitability of FNA-derived
      cDNA microarray expression profiling of breast cancers as a comprehensive genomic
      approach for studying the mechanisms of drug resistance. Our findings also
      demonstrate the potential of monitoring post-chemotherapy changes in expression
      profiles as a measure of pharmacodynamic effect and suggests that these
      approaches might yield useful results when validated by larger studies.

PMID- 12052256
TI  - Mutation analysis of the CHK2 gene in breast carcinoma and other cancers.
AB  - BACKGROUND: Mutations in the CHK2 gene at chromosome 22q12.1 have been reported
      in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is
      activated in response to DNA damage and is involved in cell-cycle pathways and
      p53 pathways. METHODS: We screened 139 breast tumors for loss of heterozygosity
      at chromosome 22q, using seven microsatellite markers, and screened 119 breast
      tumors with single-strand conformation polymorphism and DNA sequencing for
      mutations in the CHK2 gene. RESULTS: Seventy-four of 139 sporadic breast tumors
      (53%) show loss of heterozygosity with at least one marker. These samples and 45
      tumors from individuals carrying the BRCA2 999del5 mutation were screened for
      mutations in the CHK2 gene. In addition to putative polymorphic regions in short
      mononucleotide repeats in a non-coding exon and intron 2, a germ line variant
      (T59K) in the first coding exon was detected. On screening 1172 cancer patients
      for the T59K sequence variant, it was detected in a total of four breast-cancer
      patients, two colon-cancer patients, one stomach-cancer patient and one ovary
      cancer patient, but not in 452 healthy individuals. A tumor-specific 5' splice
      site mutation at site +3 in intron 8 (TTgt [a --> c]atg) was also detected.
      CONCLUSION: We conclude that somatic CHK2 mutations are rare in breast cancer,
      but our results suggest a tumor suppressor function for CHK2 in a small
      proportion of breast tumors. Furthermore, our results suggest that the T59K CHK2
      sequence variant is a low-penetrance allele with respect to tumor growth.

PMID- 12052257
TI  - Genetic determinants of mammographic density.
AB  - BACKGROUND: Changes in breast density are highly correlated with steroid hormone
      exposure. MATERIALS AND METHODS: In a cross-sectional study of 396 Caucasian and
      African-American women, we evaluated whether polymorphisms in genes involved in
      steroid hormone biosynthesis and metabolism, CYP17 (T27C), COMT (Val158Met),
      17HSDB1 (Ser312Gly) and 3HSDB1 (Asn367Thr), predict mammographic density. We also
      evaluated whether associations vary by menopausal and hormone replacement therapy
      status. RESULTS: We found no strong consistent relationships between
      polymorphisms in these genes and breast density. African-American women
      homozygous for the Thr allele of 3HSDB1 had increased density (the absolute
      difference versus the Asn/Asn genotype was +19.7%; P trend = 0.02), while
      Caucasian homozygous women had decreased density (-5.1%; P trend = 0.04). Among
      premenopausal women, carriers of the Ser allele had (not significantly) greater
      density (versus Gly/Gly genotype: +7.1%; P trend = 0.07). In addition, among
      current users of hormone replacement therapy, we observed that women with the low
      activity Met/Met genotype of COMT had greater breast density (versus the Val/Val
      genotype: +11.7%; P trend = 0.01). CONCLUSION: Additional large studies
      evaluating these and other candidate breast cancer genes will be required to
      determine what proportion, if any, of the interindividual differences in breast
      density are due to underlying genetic variation in genes involved in steroid
      hormone biosynthesis or metabolism.

PMID- 12052258
TI  - Hospital competition, resource allocation and quality of care.
AB  - BACKGROUND: A variety of approaches have been used to contain escalating hospital
      costs. One approach is intensifying price competition. The increase in price
      based competition, which changes the incentives hospitals face, coupled with the
      fact that consumers can more easily evaluate the quality of hotel services
      compared with the quality of clinical care, may lead hospitals to allocate more
      resources into hotel rather than clinical services. METHODS: To test this
      hypothesis we studied hospitals in California in 1982 and 1989, comparing
      resource allocations prior to and following selective contracting, a period
      during which the focus of competition changed from quality to price. We estimated
      the relationship between clinical outcomes, measured as risk-adjusted-mortality
      rates, and resources. RESULTS: In 1989, higher competition was associated with
      lower clinical expenditures levels compared with 1982. The trend was stronger for
      non-profit hospitals. Lower clinical resource use was associated with worse risk
      adjusted mortality outcomes. CONCLUSIONS: This study raises concerns that cost
      reductions may be associated with increased mortality.

PMID- 12052259
TI  - The role of the Zn(II) binding domain in the mechanism of E. coli DNA
      topoisomerase I.
AB  - BACKGROUND: Escherichia coli DNA topoisomerase I binds three Zn(II) with three
      tetracysteine motifs which, together with the 14 kDa C-terminal region, form a 30
      kDa DNA binding domain (ZD domain). The 67 kDa N-terminal domain (Top67) has the
      active site tyrosine for DNA cleavage but cannot relax negatively supercoiled
      DNA. We analyzed the role of the ZD domain in the enzyme mechanism. RESULTS:
      Addition of purified ZD domain to Top67 partially restored the relaxation
      activity, demonstrating that covalent linkage between the two domains is not
      necessary for removal of negative supercoils from DNA. The two domains had
      similar affinities to ssDNA. However, only Top67 could bind dsDNA with high
      affinity. DNA cleavage assays showed that the Top67 had the same sequence and
      structure selectivity for DNA cleavage as the intact enzyme. DNA rejoining also
      did not require the presence of the ZD domain. CONCLUSIONS: We propose that
      during relaxation of negatively supercoiled DNA, Top67 by itself can position the
      active site tyrosine near the junction of double-stranded and single-stranded DNA
      for cleavage. However, the interaction of the ZD domain with the passing single
      strand of DNA, coupled with enzyme conformational change, is needed for removal
      of negative supercoils.

PMID- 12052260
TI  - Mutational analysis of human profilin I reveals a second PI(4,5)-P2 binding site
      neighbouring the poly(L-proline) binding site.
AB  - BACKGROUND: Profilin is a small cytoskeletal protein which interacts with actin,
      proline-rich proteins and phosphatidylinositol 4,5-bisphosphate (PI(4,5)-P2).
      Crystallography, NMR and mutagenesis of vertebrate profilins have revealed the
      amino acid residues that are responsible for the interactions with actin and
      poly(L-proline) peptides. Although Arg88 of human profilin I was shown to be
      involved in PI(4,5)-P2-binding, it was suggested that carboxy terminal basic
      residues may be involved as well. RESULTS: Using site directed mutagenesis we
      have refined the PI(4,5)-P2 binding site of human profilin I. For each mutant we
      assessed the stability and studied the interactions with actin, a proline-rich
      peptide and PI(4,5)-P2 micelles. We identified at least two PI(4,5)-P2-binding
      regions in human profilin I. As expected, one region comprises Arg88 and overlaps
      with the actin binding site. The second region involves Arg136 in the carboxy
      terminal helix and neighbours the poly(L-proline) binding site. In addition, we
      show that adding a small protein tag to the carboxy terminus of profilin strongly
      reduces binding to poly(L-proline), suggesting local conformational changes of
      the carboxy terminal alpha-helix may have dramatic effects on ligand binding.
      CONCLUSIONS: The involvement of the two terminal alpha-helices of profilin in
      ligand binding imposes important structural constraints upon the functions of
      this region. Our data suggest a model in which the competitive interactions
      between PI(4,5)-P2 and actin and PI(4,5)-P2 and poly(L-proline) regulate profilin
      functions.

PMID- 12052261
TI  - Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3
      response to short-term treatment with 1,25-dihydroxyvitamin D3 in vivo.
AB  - BACKGROUND: Although much is known about the regulation of osteoclast (OC)
      formation and activity, little is known about OC senescence. In particular, the
      fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is
      evidence that the normal fate of OC is to undergo apoptosis (programmed cell
      death). We have investigated the effect of short-term application of high dose
      1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat
      model. METHODS: OC recruitment, augmentation and apoptosis was visualised and
      quantitated by staining histochemically for tartrate resistant acid phosphatase
      (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end
      labelling and histomorphometric analysis. RESULTS: Short-term treatment with high
      dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow
      resulting in a short-lived increase in OC numbers. This was rapidly followed by
      an increase in the number of apoptotic OC and their subsequent removal. The
      response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher
      doses producing stronger, more rapid responses and the response in the tibiae
      being consistently stronger and more rapid than in the vertebrae. CONCLUSIONS:
      This study demonstrates that (1) after recruitment, OC are removed from the
      resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to
      identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or
      in situ DNA fragmentation end labelling can be used to identify apoptotic OC in
      vivo.

PMID- 12052263
TI  - Should we put angiotensin-converting enzyme inhibitors in the water supply?

PMID- 12052262
TI  - Carpal alignment in distal radial fractures.
AB  - BACKGROUND: Carpal malalignment following the malunited distal radial fracture is
      described to develop as an adaptation to realign the hand to the malunion. It
      worsens gradually after healing of the fracture due to continued loading of the
      wrist. It is also reported to develop during the immobilization itself rather
      than after fracture healing. The present work was aimed to study the natural
      course and the quantitative assessment of such adaptive carpal realignment
      following distal radial fracture. METHODS: In a prospective study, 118 distal
      radial fractures treated with different modalities were followed-up with serial
      radiographs for a year for assessment of various radiological parameters.
      RESULTS: Two patterns of carpal malalignment were identified depending upon the
      effective radio-lunate flexion (ERLF) measured on pre-reduction radiographs. The
      midcarpal malalignment was seen in 98 radial fractures (83%) with the lunate
      following the dorsiflexed fracture fragment and a measured ERLF of less than 25
      degrees. The second pattern of radio-carpal malalignment showed the fracture
      fragment to dorsiflex without taking the lunate with a measured ERLF of more than
      25 degrees. The scaphoid did not follow the fracture fragment in both the
      patterns of malalignment. CONCLUSION: It is better to assess distal radial
      fractures for any wrist ligamentous injury on the post-reduction film with the
      restored radial anatomy than on the pre-reduction film since most carpal
      malalignments get corrected with the reduction of the fracture. Similar carpal
      malalignment reappear with the redisplacement of the fracture as seen in pre
      reduction radiographs and develops during the immobilization rather than as a
      later compensatory mechanism for the malunion.

PMID- 12052264
TI  - Infectious burden and atherosclerosis.

PMID- 12052266
TI  - Choice of agents to limit the coagulation cascade in acute coronary syndromes.
AB  - Arterial thrombosis, the predominant event in acute coronary syndromes (ACS), is
      the end-result of endothelial cell dysfunction, impaired vascular
      thromboresistance, and sudden atheromatous plaque disruption, each occurring amid
      a backdrop of inflammation and inflammatory mediators. Because the contribution
      of individual coagulation proteins to coronary arterial thrombosis varies from
      modest to marked, selective pharmacologic targeting is both pathobiologically
      sound and clinically preferred. The development of second-generation
      anticoagulants with broadened therapeutic windows represents an advance in the
      management of ACS.

PMID- 12052265
TI  - The role of pharmacotherapy and catheter-based intervention in the management of
      patients with non-ST-segment elevation acute coronary syndromes.
AB  - The American College of Cardiology/American Heart Association Task Force on
      Practice Guidelines has published recommendations regarding diagnosis and
      treatment of patients with non-ST-segment elevation (NSTE) acute coronary
      syndromes (ACS). The acute ischemia pathway presented in these guidelines
      encompasses both an early invasive strategy and an early conservative strategy.
      The recognition of the role of platelet biology in ACS led to the development of
      glycoprotein (GP) IIb/IIIa receptor antagonists for the management of patients
      with NSTE ACS. Based on studies of risk stratification models for NSTE ACS, as
      well as a better understanding of the underlying biology of serum markers of
      myocardial necrosis, refinements have been made in identifying which patients
      benefit most from intravenous platelet receptor antagonism and the use of early
      invasive strategies. The available data suggest that for the NSTE ACS patient
      with intermediate- to high-risk features, the early initiation of intravenous
      platelet receptor antagonism with a small molecule GP IIb/IIIa receptor blocker,
      followed by timely cardiac catheterization with attempts at revascularization is
      the superior management strategy. In the majority of cases where such patients
      present to a facility without cardiac catheterization capability, stabilization
      with antiplatelet, antithrombotic, and anti-ischemic therapies should be
      undertaken prior to timely tertiary percutaneous coronary intervention referral.

PMID- 12052267
TI  - The role of inflammation and infection in the pathogenesis and evolution of
      coronary artery disease.
AB  - Inflammation plays a major role in the initiation and progression of coronary
      artery disease (CAD) and the precipitation of acute coronary events. However, the
      inflammatory triggers are poorly understood. Noninfectious stimuli undoubtedly
      play a role. Recently, chronic infection has been proposed as another
      inflammatory trigger. Histologically, unstable atherosclerotic plaque contains
      activated macrophages and T lymphocytes, adhesion molecules, chemokines and
      cytokines, matrix-degrading enzymes, and prothrombotic factors. Circulating
      inflammatory markers such as C-reactive protein, fibrinogen, and interleukins are
      increased in high-risk cohorts and predict future risk. Experimental models and
      human studies have supported a role of infection in the promotion of
      atherosclerosis. Although the independent predictive value of seropositivity to
      individual agents has varied, total pathogen burden, the sum of seropositivities
      to many bacterial and viral vectors, has been more consistent. Whether
      antibiotics or vaccines will be useful in CAD prevention remains to be shown.
      Meanwhile, therapies with proven vascular anti-inflammatory effects (eg, diet,
      exercise, smoking cessation, aspirin, statins) should be optimized.

PMID- 12052268
TI  - Early use of statins in acute coronary syndromes.
AB  - This review examines the use of HMG-CoA reductase inhibitor (statin) medications
      early in the clinical course of acute coronary syndrome. Available data
      demonstrate that there are clear clinical benefits to this practice. Numerous
      previous studies have documented the primary and secondary benefits of statins in
      the prevention of coronary events. Recent trials show that when statins are used
      during hospital admissions for acute coronary syndrome (ACS), patients experience
      decreased recurrent myocardial infarction, lower death rates, and fewer repeat
      hospitalizations for ischemia or revascularization. Several studies suggest that
      the positive effects of statins on plaque stabilization, inflammation,
      thrombosis, and endothelial function may be independent of lipid levels. There is
      also an emerging view that beneficial lipid-lowering with statins in high-risk
      patients has no lower limit. This information suggests that all patients admitted
      for ACS should be treated with statins, regardless of cholesterol levels.

PMID- 12052269
TI  - Glycoprotein receptor inhibitors in the management of acute coronary syndromes.
AB  - Coronary thrombosis and the risk of clinical adverse events remains high despite
      considerable advances in the management of acute coronary syndromes (ACS) with
      the combined use of aspirin, heparin, fibrinolytic therapy, and percutaneous
      coronary intervention (PCI). Platelet aggregation and thrombosis play a key role
      in the pathogenesis of unstable coronary syndromes. Over the past several years,
      multiple placebo-controlled trials involving more than 50,000 ACS patients have
      shown that blockade of the platelet receptor glycoprotein (GP) IIb/IIIa, the
      final pathway in platelet aggregation, reduces the incidence of ischemic
      complications among patients with ACS. Three agents (abciximab, eptifibatide, and
      tirofiban) are currently approved for use with aspirin and heparin in the
      management of ACS or during percutaneous coronary intervention. They have
      consistently been shown to reduce the incidence of death or myocardial infarction
      in the ACS population including the patients not routinely scheduled for early
      revascularization. They provide an augmented treatment effect among high-risk ACS
      patients, particularly those who have a baseline troponin-t-positive status.
      Recently published practice guidelines have recommended their use in high-risk
      patients with ACS and all those undergoing PCI.

PMID- 12052270
TI  - Glycoprotein IIb/IIIa receptor inhibitor-thrombolytic combination therapy for
      acute myocardial infarction.
AB  - Over the past two decades, we have witnessed a large decrease in the death and
      complication rate of patients experiencing acute myocardial infarction (MI), due
      to our ability to restore blood flow to infarct-related arteries. Therapies
      include strategies to inhibit platelet function and induce fibrinolysis, and
      mechanical reperfusion with percutaneous intervention. Despite decreases in
      morbidity and mortality with thrombolytic therapy, reperfusion rates remain less
      than optimal. With standard fibrinolytic therapy in combination with aspirin, it
      is thought that thrombolytic-induced platelet activation may be an important
      reason for failure to induce perfusion, or maintain reperfusion in the infarct
      related artery. In the past 10 years we have moved from platelet inhibition with
      aspirin to newer, more potent platelet inhibitors such as glycoprotein (GP)
      IIb/IIIa antagonists. Recent trials have evaluated the efficacy and safety of
      combining thrombolytic drugs with GP IIb/IIIa receptor antagonists. Future trends
      may use combination therapy as a part of a mechanical strategy, using these
      medications to induce early reperfusion as the patient is prepared for
      percutaneous intervention. This review summarizes recently published trials using
      combination thrombolytic and GP IIb/IIIa receptor inhibitor therapy in the
      treatment of acute MI.

PMID- 12052272
TI  - Unfractionated versus fractionated heparin for percutaneous coronary
      intervention.
AB  - Since the advent of percutaneous coronary intervention (PCI), intravenous
      unfractionated heparin has been the primary antithrombotic therapy to prevent
      periprocedural ischemic complications. As compared with unfractionated heparin,
      low molecular weight heparins (LMWHs) have a greater bioavailability and a more
      predictable therapeutic response. In several recent studies of patients
      undergoing PCI, LMWHs have been shown to be as safe and effective as
      unfractionated heparin; given their better pharmacokinetic profile and the lack
      of need for coagulation monitoring, they have the potential to replace
      unfractionated heparin during coronary interventions. This article reviews the
      current status of anticoagulation therapy with unfractionated heparin and LMWHs
      in the cardiac catheterization laboratory.

PMID- 12052271
TI  - Lipid-lowering therapies in the management of acute coronary syndromes.
AB  - Despite the significant advances made in the treatment of acute coronary
      syndromes (ACS) with antiplatelet and antithrombotic therapy, the risk of serious
      complications remains high, especially in the first few months following an acute
      coronary event. Although lipid-lowering therapy in patients with significant risk
      factors (primary prevention) or stable coronary disease (secondary prevention) is
      known to improve long-term survival, patients with a recent ACS were specifically
      excluded from the early statin trials. However, the use of lipid-lowering agents
      (principally statins) during hospitalization or in the period immediately
      following an acute coronary event has recently been studied. Statin therapy in
      this setting has been shown to reduce angina, rehospitalization, and mortality.
      Improved outcomes associated with lipid-lowering therapy in ACS may be mediated
      through beneficial effects on plaque stabilization, endothelial function,
      inflammation, and thrombus formation. This paper reviews the evidence supporting
      the potential benefits and mechanisms of statin therapy in the management of ACS.
      Clinical guidelines to achieve optimal lipid management are also discussed.

PMID- 12052274
TI  - New biomarkers in the risk stratification of patients with suspected acute
      myocardial infarction.
AB  - The acute coronary syndromes (ACS) remain a diagnostic and prognostic challenge
      for today's physician. Over the past decade, studies have identified several
      serologic biomarkers to aid the clinician in assessing risk and predicting
      outcomes in ACS. Still others are being identified that show promise for
      increasing the accuracy with which this risk is assessed. However, further
      research remains necessary to identify the perfect cardiac biomarker or
      combination of markers and to define their roles in clinical management of ACS
      patients.

PMID- 12052273
TI  - Early invasive strategies for acute coronary syndromes.
AB  - Early coronary angiography and percutaneous or operative revascularization is now
      the treatment of choice for both ST- and non-ST-segment elevation acute coronary
      syndromes (ACS). In non-ST-segment elevation ACS this strategy produces a 18% to
      22% reduction in ischemic outcomes at 6 months and prevents 1.7 deaths, 2.0
      nonfatal infarcts and 20 readmissions per 100 treated patients at 1-year follow
      up. Early angiography allows definition of coronary anatomy and assessment of
      left ventricular function, both important predictors of long-term risk.
      Intracoronary stenting and intravenous glycoprotein IIb/IIIa antagonists have
      improved outcome in percutaneous revascularization and should be used in the
      majority of ACS patients undergoing PCI. Initial costs are higher with an early
      invasive strategy; however, these are offset by reductions in rehospitalizations
      and later ischemic complications.

PMID- 12052276
TI  - Clinical trials of treatments for stroke.
AB  - The "gold standard" for therapeutic trials is the prospective, double-blind,
      placebo-controlled, multicenter trial. However, they are relatively clumsy
      instruments for discovering innovative new treatments. This article briefly
      reviews selected clinical trials of treatments for stroke, including stroke
      rehabilitation, published during 2001 and the first 2 months of 2002. It also
      reviews other types of studies, including close observations of single patients,
      which can have a valuable role in generating useful new knowledge.

PMID- 12052275
TI  - New scavenger receptors and their functions in atherogenesis.

PMID- 12052277
TI  - Robotics in the rehabilitation treatment of patients with stroke.
AB  - Stroke is the leading cause of permanent disability despite continued advances in
      prevention and novel interventional treatments. Post-stroke neuro-rehabilitation
      programs teach compensatory strategies that alter the degree of permanent
      disability. Robotic devices are new tools for therapists to deliver enhanced
      sensorimotor training and concentrate on impairment reduction. Results from
      several groups have registered success in reducing impairment and increasing
      motor power with task-specific exercise delivered by the robotic devices.
      Enhancing the rehabilitation experience with task-specific repetitive exercise
      marks a different approach to the patient with stroke. The clinical challenge
      will be to streamline, adapt, and expand the robot protocols to accommodate
      healthcare economies, to determine which patients sustain the greatest benefit,
      and to explore the relationship between impairment reduction and disability
      level. With these new tools, therapists will measure aspects of outcome
      objectively and contribute to the emerging scientific basis of neuro
      rehabilitation.

PMID- 12052278
TI  - New developments in stroke rehabilitation.
AB  - There is increasing evidence that environmental and neuropharmacologic treatments
      enhance stroke recovery. Functional magnetic resonance imaging and transcranial
      magnetic stimulation have significantly broadened our understanding of the
      neuroanatomic relationships involved in recovery from brain injury due to stroke.
      These tools have also demonstrated the role for pharmacologic enhancement of
      cortical plasticity coupled with behavioral interventions. Robot-assisted therapy
      and partial body weight-supported treadmill gait training have demonstrated the
      role for technologic intervention in the modern neuro-rehabilitation setting.
      Current research using hemi-field ocular prisms and patching techniques suggest a
      role in the rehabilitation of hemianopsia and visual neglect. Finally, many
      advances have been made in the understanding of common stroke complications, such
      as depression, dysphagia, venous thromboembolic disease, incontinence, and
      spasticity.

PMID- 12052279
TI  - Stroke-related dementia.
AB  - Three months after a stroke, one quarter to one third of patients meet
      operationalized criteria for dementia, and an even greater proportion have
      cognitive impairment short of dementia. A significant number of these patients
      had mental deterioration before the stroke, implying an underlying
      neurodegenerative process. Current diagnostic criteria do not reflect these
      facts, and in addition to artificially using cerebrovascular disease to
      differentiate Alzheimer's disease and vascular dementia, they do not allow
      researchers and clinicians to identify subjects at risk in the early stages of
      cognitive decline. To be clinically useful, a broader concept of cognitive
      impairment in the setting of vascular disease needs to be developed based on data
      collected prospectively using cohorts of stroke patients.

PMID- 12052280
TI  - Computerized approaches to communication retraining after stroke.
AB  - Augmentative and alternative communication (AAC) strategies traditionally have
      been designed for individuals for whom oral speech is not a viable option. Common
      clinical practice has expanded AAC use to a tool for cognitive retraining or
      remediation. Although technologic developments offer the potential for vastly
      improved communication and inclusion for some individuals with severe
      communication disorders, technology alone does not result in successful
      communication. Although AAC interventions have become increasingly common across
      the age range, the research base underlying the design of AAC technology,
      intervention strategies, and treatment potential across communication disorders
      remains quite limited. To move beyond the traditional application of AAC
      strategies as a communication modality for persons with severe motor disorders to
      applications for persons with cognitive/linguistic disorders, three interrelated
      areas of research requiring further investigations are discussed. These include
      the following: use of AAC as a research tool to provide theoretical insights into
      the nature of normal and impaired language and cognition; development of AAC
      strategies as treatment tools to facilitate language recovery and use (production
      and comprehension); and studies that evaluate the efficacy of applying AAC
      strategies as communication modalities for individuals with acquired
      cognitive/linguistic communication disorders.

PMID- 12052281
TI  - Stroke-related depression.
AB  - Stroke represents a major health problem in the United States and most European
      and Asian countries. Depression is probably the most common and serious emotional
      disorder following stroke. Post-stroke depression (PSD) has frequently been
      overlooked and left untreated. Prevention of PSD or successful intervention in
      the early phase may prevent premature deaths as well as facilitate
      rehabilitation, reduce costs, and improve quality of life. Stroke is clearly a
      risk factor for depression, and recent evidence suggests that depression
      increases the risk for stroke, although the mechanisms by which depression leads
      to stroke remain to be clarified. Once PSD has developed, numerous studies have
      documented its adverse effect on cognitive recovery, physical recovery, and
      mortality. Taken together, these studies support the necessity of identifying and
      treating this condition.

PMID- 12052283
TI  - Recent developments in diagnosis and intervention for aspiration and dysphagia in
      stroke and other neuromuscular disorders.
AB  - This review discusses the impact of the evidence-based report on dysphagia
      diagnosis and treatment in stroke patients prepared in 1999 by ECRI under
      contract with the Agency for Healthcare Research and Quality (AHRQ). Subsequent
      research findings are highlighted and research design and reporting problems in
      the field are discussed. Progress has been made toward standardizing training and
      rating of videofluoroscopic studies of swallowing (VFSS); however, a consensus
      does not yet exist. A randomized, controlled trial demonstrated that treatment
      directed by fiber-optic endoscopic evaluation of swallowing with sensory testing
      (FEESST) or VFSS resulted in approximately equivalent pneumonia rates. These two
      different methods provide both overlapping and complementary information. There
      is discussion of the research design problems of mixed patients versus
      homogeneous populations, case-control diagnostic studies, inappropriate
      calculations of diagnostic sensitivity/specificity using imperfect "gold
      standards," the lack of concurrent control groups in treatment studies, and the
      misuse of statistical significance tests and P values in examining matching of
      patient characteristics in comparative studies and in identifying important
      variables in regression analysis.

PMID- 12052282
TI  - Treatment of lipid disorders after stroke.
AB  - The efficacy of lipid disorder therapy for the primary and secondary prevention
      of coronary heart disease is established. There are, however, no completed
      studies specifically directed at reducing the risk of stroke with lipid therapy.
      Although observational cohort studies have failed to demonstrate an association
      between lipid disorders and stroke incidence, recently completed trials of
      subjects at risk for coronary heart disease have shown that statins and fibric
      acid derivatives reduce not only the risk of myocardial infarction and death, but
      also that of brain infarction and transient ischemic attacks. Lipid drugs are
      well tolerated and treatment complications are relatively low. It seems prudent
      to conclude that the stroke patient with an undesirable lipid profile who has a
      history of coronary heart disease should receive specific treatment for the lipid
      disorder. Recommendations are more problematic for stroke patients with lipid
      disorders but no history of coronary heart disease; most should receive therapy
      for primary prevention of heart disease. Lipid treatment trials focused on stroke
      risk reduction are urgently needed.

PMID- 12052284
TI  - Warfarin versus aspirin in the secondary prevention of stroke: the WARSS study.
AB  - The role of anticoagulation in the secondary prevention of noncardioembolic
      stroke has long been an area of debate. Previous evidence has shown that
      anticoagulation is unsafe at an International Normalized Ratio between 3.0 and
      4.5. Results of the recently published Warfarin-Aspirin Recurrent Stroke Study
      (WARSS) suggest that there is no difference between warfarin and aspirin in the
      prevention of recurrent ischemic stroke or death or in the rate of major
      hemorrhage. Differences in the therapeutic interventions used may have had an
      effect on the differences in endpoints achieved as compared with previous
      studies. Results of ongoing trials are anticipated to further clarify the role of
      anticoagulation in the secondary prevention of stroke.

PMID- 12052298
TI  - What's new in childhood asthma?

PMID- 12052299
TI  - Six of the best: cystic fibrosis.

PMID- 12052300
TI  - What's happening in respiratory infection?

PMID- 12052301
TI  - What's new in respiratory allergy?
AB  - The past 10 years have seen important advances in our understanding of allergic
      respiratory disease and the targets for potential therapies. Sensitisation and
      triggering of allergic reactions now appear to be better understood at a clinical
      and molecular level. Environmental intervention studies are underway attempting
      to reduce the sensitisation and the triggering of symptoms. Therapeutic
      intervention studies targeting key pathways in the allergic cascade are also
      taking place. This paper will assess both of these aspects of respiratory
      allergy, updating readers on the new evidence in our quest to understand how and
      when sensitisation occurs and also how we might be able to control triggered
      reactions using targeted therapeutics against specific elements of the allergic
      cascade.

PMID- 12052302
TI  - Epithelial antimicrobial peptides and proteins: their role in host defence and
      inflammation.
AB  - Various antimicrobial mechanisms act in concert to protect the lung from
      infection by forming an efficient host defence system. Most microbial challenges
      are counteracted by elements of the innate immune system and antimicrobial
      peptides and proteins have been identified as key components of innate immunity.
      Although phagocytes are an important cellular source of these so-called
      endogenous antibiotics, it is now recognized that the airway epithelium is also a
      major site of synthesis. Antimicrobial peptides and proteins kill a wide variety
      of micro-organisms. Their importance is illustrated by the observation that in
      cystic fibrosis changes in the airway surface fluid may result in a dysfunction
      of these components. Recent studies have revealed other functions of these
      molecules showing they may link innate and adaptive immunity and appear to be
      involved in the regulation of inflammation and tissue repair.

PMID- 12052303
TI  - The neonatal chest X-ray.
AB  - The chest X-ray is the most valuable imaging modality in the assessment of the
      neonate with respiratory distress. Whilst many of the radiological appearances
      are relatively non-specific, integration of the clinical features with the X-ray
      appearances will help the clinician arrive at the correct diagnosis in most
      cases. In a minority of infants, particularly those with a congenital
      malformation of the chest or airways other imaging modalities may be required.
      This paper will describe the radiological appearances of the most important
      causes of neonatal respiratory distress and highlight those situations where more
      complex investigations are necessary.

PMID- 12052304
TI  - Impact of lung inflammation on bone metabolism in adolescents with cystic
      fibrosis.
AB  - Deficits in bone mineral density resulting in premature osteopenia and
      osteoporosis have been documented in cystic fibrosis patients for over 20 years.
      A high incidence of fractures and kyphosis in the continually increasing adult
      patient population and in post-lung transplant patients has highlighted the
      problems associated with poor bone health.The aetiology of osteoporosis in CF is
      multifactorial but centres on an uncoupling in the normal balance between bone
      formation and resorption. Delayed puberty, malabsorption and reduced weight
      bearing exercise can result in inadequate bone mineral accretion in childhood and
      adolescence. Corticosteroid use and pro-inflammatory cytokines associated with
      infective respiratory exacerbations can accelerate bone loss. Dual energy X-ray
      absorptiometry is the most commonly available technique to measure bone mineral
      density. All patients should be scanned at least every 2 years from adolescence.
      The treatment of established disease with bisphosphonates shows encouraging early
      results.

PMID- 12052305
TI  - Phenotype of CF and the effects of possible modifier genes.
AB  - Cystic fibrosis is an inherited multi-system disease, characterised by
      progressive lung disease and pancreatic insufficiency that is classically
      attributed to the dysfunction of a single gene coding for the cystic fibrosis
      transmembrane conductance regulator (CFTR). The widely diverse phenotypic
      expression of CF is likely influenced by other genetic traits separate from the
      CFTR locus or modifier genes. Many of the genes currently under study as
      potential modifiers of CF, particularly those which influence the severity of
      lung disease, are involved in the control of infection, immunity and
      inflammation. Some of these include HLA class II antigens, mannose-binding
      lectin, alpha(1)-antitrypsin and alpha(1)-antichymotrypsin, glutathione-S
      transferase, nitric oxide synthase type I, TNF-alpha, TGF-beta, IL-1beta and IL
      1Ra.

PMID- 12052306
TI  - Liver disease in children with cystic fibrosis.
AB  - Identification, evaluation and treatment of liver disease are increasingly
      important challenges in children with cystic fibrosis (CF). Liver disease usually
      presents at puberty and is receiving more attention with improved life
      expectancy. The abnormal CF transmembrane regulator protein in the apical surface
      of the biliary epithelium causes the disease. Hyperviscous bile accumulates in
      the biliary tree causing cholangiocyte and hepatocyte injury, stimulating focal
      fibrosis. Fibrosis is thought to lead on to cirrhosis over a period of years, a
      process which is usually asymptomatic. Steatosis and biliary tree anomalies
      including cholecystitis also occur. Clinical signs of liver disease appear late,
      by which time cirrhosis may be established. Early diagnosis would allow
      interventions to be evaluated but there is no gold standard for screening.
      Currently, regular clinical assessment, measurement of liver enzymes, ultrasound
      and liver biopsy are all used to evaluate liver disease in CF. Bile acid therapy
      reverses many markers of the disease but there is no good evidence that
      progression to cirrhosis can be prevented. A few children with cirrhosis
      decompensate (demonstrated by falling plasma albumin or coagulopathy) but they do
      well with liver transplantation. Children with portal hypertension as the sole
      manifestation of CF liver disease can be effectively managed with a programme of
      variceal obliteration or porto-systemic shunts.

PMID- 12052307
TI  - Psychological interventions in cystic fibrosis and asthma.
AB  - Cystic fibrosis and asthma have many psychosocial implications for patients and
      their relatives. These can stem from parental adaptational problems following
      diagnosis, negative illness perceptions, feeling 'different' and other associated
      developmental intrusions. In asthma, psychological factors arising from a variety
      of sources are known to 'trigger' attacks. For adolescents, psychological
      problems are hallmarked by loss (e.g. of identity, independence and peers) which
      results in re-appraisals of self-worth, depression and anxiety. Early
      intervention strategies and screening are crucial in ameliorating unsuccessful
      emotional adaptation and preventing chronic psychological morbidity. Behavioural
      and cognitive-behavioural interventions are particularly effective for both
      treatment-related behavioural problems (e.g. procedural distress, and poor
      feeding behaviour) and some psychological disorders (e.g. anxiety and
      depression). However, outcome depends on patients' motivation to change and
      willingness to collaborate. Where this is absent, less directive, but nonetheless
      effective, psychotherapies are utilised. Family therapy is also considered useful
      in addressing family dysfunction when thought to be intrinsic to the emotional
      problems.

PMID- 12052308
TI  - Rhinitis, sinusitis and asthma: one linked airway disease.
AB  - Understanding the relationship between upper and lower airways has greatly
      increased through epidemiological and pharmacological studies. Scientific
      evidence supports the concept that rhinosinusitis and asthma may be the
      expression of an inflammatory process which appears in different sites of the
      respiratory tract at different times. The implications are not only academic but
      are important for diagnostic and therapeutic purposes.

PMID- 12052309
TI  - Skeletal dysplasias and their effect on the respiratory system.
AB  - Children with skeletal dysplasia frequently have pulmonary disease which can be
      life threatening. These pulmonary problems are due to multiple aetiologies
      including thoracic and craniofacial anomalies predisposing to restrictive lung
      disease, upper airway obstruction and central apnoea. Recognition of pulmonary
      disease and early intervention improves the survival and quality of life for
      these children.

PMID- 12052320
TI  - Parental smoking: asthma and wheezing illnesses in infants and children.
AB  - Parental smoking has an important impact on asthma and wheezing illnesses in
      infants and children. In utero exposure is associated with impaired lung growth
      and wheezing illnesses, particularly in preschool children. Exposure to
      environmental tobacco smoke is associated with increased wheezing illnesses and
      increased symptoms in asthmatics. There are no consistent data to confirm an
      effect of in utero or postnatal cigarette smoke exposure on the prevalence of
      asthma but there is evidence of increased severity of symptoms. The detrimental
      effects of parental smoking on lung growth will have an impact on respiratory
      health throughout life.

PMID- 12052321
TI  - Parental smoking and respiratory tract infections in children.
AB  - The adverse health consequences of exposing children to tobacco smoke have been
      well documented. Re-calculation of the data available from cohort and cross
      sectional studies worldwide shows that between 500-2500 excess hospitalisations
      and between 1000 to 5000 excess diagnoses per 100 000 young children as result
      from respiratory infections can be directly attributed to parental smoking.
      Results of published meta-analyses support these figures, which are probably
      under-estimated because of the effects of non-differential misclassification
      bias. These excess infections are a source of preventable morbidity and have a
      high cost to the community. They also have important long-term consequences
      because children who have respiratory infections in early life are at an
      increased risk of developing asthma in later childhood. More effective strategies
      that prevent smoking in young people before they become parents have the
      potential to lead to reductions in these high rates of unnecessary morbidity in
      the next generation of children.

PMID- 12052322
TI  - Changing patterns of cigarette smoking among teenagers and young adults.
AB  - In Britain at present the highest prevalence of smoking in people aged 16 years
      and over is among 20- to 24-year-olds. At this age, 42% of men and 39% of women
      smoke, compared with the overall rates of 28% and 26%. The problem is greatest in
      the less affluent socio-economic groups. Prevalence of regular smoking among 11-
      to 15-year-olds has changed little since 1982, although in 1999 it reached one of
      its lowest points, namely 9%. More girls than boys are smoking, e.g. 25% compared
      with 21% at age 15 years. Signs of developing nicotine dependence are already
      evident even in lighter smokers. Smoking behaviour in a country appears to follow
      a pattern where men start first, followed by boys, women and then girls. In most
      industrialised countries, prevalence for each group, except teenage girls, has
      peaked and reversed. Most developing countries are at an earlier stage in the
      pattern, which must be stopped now if millions of deaths are to be avoided.

PMID- 12052323
TI  - Helping parents to stop smoking: which interventions are effective?
AB  - Parental smoking increases children's risk of respiratory illness. Encouraging
      parents not to smoke in the home helps, but stopping smoking altogether is more
      effective in reducing children's exposure. The prevalence of smoking increases
      with higher levels of social disadvantage and is therefore a major contributor to
      widening inequalities in health. Randomised trials have shown that adults can be
      helped to stop with simple advice from health professionals, behavioural support,
      nicotine replacement and antidepressants.

PMID- 12052324
TI  - Pulmonary vascular imaging.
AB  - This article is a pictorial review of the major abnormalities of the pulmonary
      vessels in children. Vascular, including lymphatic malformations have been
      covered in previous issues of this journal and so will not be described in
      detail. Many pulmonary vascular abnormalities are associated with complex
      intracardiac disorders. This article, however, focuses on extra cardiac
      abnormalities, particularly those causing pulmonary parenchymal problems.

PMID- 12052325
TI  - Leukotrienes in respiratory disease.
AB  - Arachidonic acid metabolism via 5-lipoxygenase gives rise to a group of
      biologically active lipids known as leukotrienes: leukotriene B(4), which is a
      potent activator of leukocyte chemotaxis, and cysteinyl leukotrienes (leukotriene
      C(4), D(4)and E(4)) which account for the spasmogenic activity previously
      described as slow-reacting substance of anaphylaxis. The biological actions of
      leukotrienes and the observations that leukotrienes are synthesised in the lung
      following antigen provocation and are elevated in asthma, stimulated considerable
      activity in the pharmaceutical industry to find drugs that modulate the synthesis
      or actions of leukotrienes. Three cysteinyl leukotriene antagonists (zafirlukast
      [Accolate], montelukast [Singulair] and pranlukast) and one 5-lipoxygenase
      inhibitor (zileuton) have received regulatory approval for the treatment of
      asthma. The clinical data obtained from using these drugs are generally
      consistent and complimentary. As a class the leukotriene modulators produce a
      rapid improvement in lung function after the first oral dose. Lung function
      improvements are maintained on chronic administration and are associated with
      reductions in a variety of asthma symptom scores. All of the available data are
      consistent with the hypothesis that all the leukotriene modulators exert their
      clinical benefit primarily through interference with cysteinyl leukotrienes.
      There are no compelling clinical data for an additional contribution by
      leukotriene B(4)in human asthma. In other respiratory conditions such as COPD,
      which are characterised by pronounced neutrophil infiltration, it may be that the
      chemotactic properties of leukotriene B(4)are more important and therefore
      evaluation of 5-lipoxygenase inhibitors in this condition is warranted. The
      introduction of the leukotriene modulators into clinical practice is the
      culmination of over 60 years of research since the initial discovery of the slow
      reacting substances. The leukotriene modulators, and in particular the cysteinyl
      leukotriene antagonists, provide respiratory physicians with an oral therapeutic
      option and have set an efficacy standard which new oral anti-inflammatory
      approaches will have to beat.

PMID- 12052326
TI  - Host-bacterial interactions in the initiation of inflammation.
AB  - The respiratory epithelium provides both a physical and an immunological barrier
      to inhaled pathogens. In the normal host, innate defences prevent bacteria from
      activating inflammation by providing efficient muco-ciliary clearance and
      antimicrobial activity. Bacteria that persist in the airway lumen, as in cystic
      fibrosis, activate both the professional immune cells in the respiratory mucosa
      as well as the more abundant airway epithelial cells. As most of the bacteria
      become entrapped in airway mucin, shed bacterial products such as pili, flagella,
      peptidoglycan and lipopolysaccharide from lysed bacteria are likely to be the
      stimuli most important in activating epithelial signalling. The airway cells
      respond briskly to bacterial components through several signalling systems which
      activate epithelial expression of pro-inflammatory cytokines and chemokines.
      These signals recruit neutrophils to the airways where they eliminate the
      contaminating bacteria causing inflammation and the ensuing clinical signs of
      infection.

PMID- 12052328
TI  - Non-compliance in adolescents with chronic lung disease: causative factors and
      practical approach.
AB  - Compliance with medical therapies may be considered a challenge in many age
      groups but especially so in adolescence. The adolescent patient with chronic lung
      disease may struggle to progress smoothly through the phases of adolescence
      because of fears of peer rejection and isolation occurring as a result of social,
      emotional and physical consequences of their underlying lung disease and its
      treatment. Non-compliance can be viewed as a scale from episodic compliance to
      frequent compliance with patients moving between ends of the spectrum. Health
      professionals need to consider the likely degree of compliance with therapies
      that they recommend, discuss the issue of compliance and the consequences of non
      compliance with the adolescent patient and arrive at a workable compromise. This
      article discusses persistent asthma, cystic fibrosis and advanced neuromuscular
      disease to illustrate practical approaches to enhancing patient compliance in
      adolescence.

PMID- 12052327
TI  - Glucose intolerance in cystic fibrosis patients.
AB  - Diabetes mellitus has evolved as a complication because of increased longevity of
      patients with cystic fibrosis (CF). CF-related diabetes (CFRD) is associated with
      increased morbidity and mortality, therefore, prompt diagnosis and aggressive
      management are important. The prevalence of CFRD increases with age with an age
      dependent incidence rate of 5% per year; at 30 years 50% of patients are
      diabetic. CFRD develops insidiously. Screening by measurements of fasting, random
      plasma glucose or glycated haemoglobin A(1c), alone or in combination, do not
      reliably identify CFRD as compared with the 2-hour plasma glucose value measured
      during an oral glucose tolerance test. Reasons for the development of CFRD are
      not fully understood. Generally, patients are characterised by the presence of a
      class I, II or III CF mutation, exocrine pancreatic insufficiency, impaired and
      delayed insulin secretion, impaired glucagon secretion, normal insulin
      sensitivity and an increased insulin clearance rate. One can speculate that for
      endocrine dysfunction to deteriorate from normal to impaired glucose tolerance
      and then to CFRD, there must be an additional diabetes mellitus-related genetic
      defect.CFRD leads to deterioration of overall clinical CF status but insulin
      therapy can revert this. Late diabetic complications may develop as in other
      types of diabetes although macrovascular complications are rare. CFRD patients
      have an increased mortality compared to non-diabetic CF patients. Insulin therapy
      is the preferred treatment.

PMID- 12052329
TI  - Genetic contributions to rare childhood lung diseases.
AB  - Epidemiological studies have suggested that many rare diseases with respiratory
      involvement have a genetic component. Molecular advances have increased the
      understanding of the pathophysiology of these diseases which has led to better
      diagnostic and prognostic methods. There may be many genes responsible for
      diseases such as primary ciliary dyskinesia and systemic lupus erythematosus in
      addition to the effect of modifier genes. The genotype:phenotype correlation in
      these diseases remains to be elucidated. In some diseases, such as familial
      dysautonomia and sickle cell, the gene has been identified which allows for
      accurate pre-natal testing. Further, in diseases where the genetic abnormality is
      known, such as chronic granulomatous disease, gene therapy remains a realistic
      prospect and phase I studies are about to commence or currently underway. This
      article reviews those rare diseases in which there is or is likely to be a
      significant genetic contribution.

PMID- 12052330
TI  - Newcastle disease outbreaks in western China were caused by the genotypes VIIa
      and VIII.
AB  - Twelve Newcastle disease virus (NDV) strains were isolated from chickens involved
      in outbreaks of Newcastle disease (ND) in western China (Shaanxi, Gansu,
      Xinjiang, Qinghai and Guangxi provinces) between 1979 and 1999. All strains were
      determined to be velogenic by plaque formation, the mean death time (MDT) of
      embryonated eggs, and the intracerebral pathogenicity index (ICPI). For
      preparation of virus RNA, the acid guanidinium-thiocyanate method was used. A
      908bp fragment of nucleotide was amplified by RT-PCR starting from the N terminal
      of the F gene and the PCR segments were cloned into the PGEM-T vector and
      sequenced. The similarities of the nucleotide sequences (1-519bp) and predicted
      amino acid sequences of the F gene (1-125) were analyzed by comparing the 12 NDV
      isolates with the NDV vaccine strains Lasota, B1, H1 and V4, with classical NDV
      strains and recent epizootic strains. Phylogenetic analysis demonstrated that all
      strains were of two novel genotypes; the NDV strains that caused the outbreak of
      ND in western China during 1998-1999 was of the genotype VIIa, whereas the
      strains from the Qinghai province (1979-1985) were of genotype VIII, which has
      been found predominately in southern Africa.

PMID- 12052331
TI  - Isolation of Salem virus, a novel equine paramyxovirus, and assessment of its
      etiologic role in a disease outbreak.
AB  - Salem virus (SalV) is a recently identified equine virus belonging to the family
      Paramyxoviridae. The only known isolate was obtained from a horse that was
      involved in a disease outbreak of undetermined nature and the circumstances of
      its isolation suggested an etiologic role. However, the experimental infection of
      a colostrum-deprived foal failed to reproduce the disease; only mild neutropenia
      and temperature elevation were recorded. An additional attempt to establish an
      etiological relationship with the disease was made by conducting a retrospective
      evaluation of the serological profiles of animals involved in the outbreak.
      Animals reported as being affected by the disease according to a comprehensive
      United States Department of Agriculture (USDA) database were found to be 48%
      (n=27) positive for antibodies to SalV, but the percent positive for all horses,
      affected and unaffected, was actually higher at 56% (n=62). For 15 affected
      horses for which paired acute and convalescent serum specimens were available, no
      unequivocal seroconversions to SalV were identified. Furthermore, the horse from
      which SalV was isolated was not listed as one of the animals affected by the
      disease. In total, the evidence suggests that SalV was not the etiological agent
      of the disease and that its isolation was fortuitous.

PMID- 12052332
TI  - Single-step purification and evaluation of recombinant BP26 protein for
      serological diagnosis of Brucella ovis infection in rams.
AB  - To investigate the value of the BP26 protein in the serological diagnosis of
      ovine brucellosis caused by Brucella ovis, recombinant BP26 protein was produced
      in Echerichia coli and purified for use in an indirect enzyme-linked
      immunosorbent assay (I-ELISA). The majority of the recombinant protein was
      recovered from the supernatant of sonicated recombinant E. coli cells in a
      soluble form. This facilitated the purification of the recombinant BP26 protein
      which was achieved by using ion-exchange chromatography. After one step of
      purification, the purity of the recombinant BP26 protein was analyzed by using
      SDS-PAGE, Coomassie blue staining, and Western blot with a monoclonal antibody
      (MAb) directed against the BP26 protein. The degree of purity appeared
      satisfactory so that it could be directly used in I-ELISA. Although the
      recombinant BP26-ELISA appeared less useful than I-ELISA using the B. ovis hot
      saline (HS) extract as antigen, the high number of sera from B. ovis infected
      rams found positive (90%) in the recombinant BP26-I-ELISA indicated that the BP26
      protein may be an additional suitable antigen for serological diagnosis of B.
      ovis infection in rams.

PMID- 12052333
TI  - Characterization of, and immune responses of mice to, the purified OmpA
      equivalent outer membrane protein of Pasteurella multocida serotype A:3 (Omp28).
AB  - Pasteurella multocida A:3 is a major cause of bovine pneumonia. A major antigenic
      heat-modifiable 28kDa outer membrane protein (Omp28) was previously identified.
      The purpose of this study was to purify and characterize Omp28 immunologically
      and structurally. Omp28 was extracted from N-lauroylsarcosine-insoluble protein
      preparations by a combination of detergent fractionation with Zwittergent 3-14
      and chromatography. Partial N-terminal amino acid sequence confirmed Omp28 as a
      member of the OmpA-porin family. However, porin activity could not be
      demonstrated in a lipid-bilayer assay. Heat modifiability of purified Omp28 was
      demonstrated, and Omp28 was found in outer membrane fraction of P. multocida.
      Surface exposure of Omp28 was demonstrated by partial protease digestion of
      intact bacteria, by binding of anti-Omp28 polyclonal ascites fluid to the
      bacterial surface, and by partial inhibition of anti-outer membrane antiserum
      binding by previous incubation of the bacteria with anti-Omp28 serum. CD-1 mice
      vaccinated with purified Omp28 developed a significant antibody titer (P<0.05)
      compared to the control treatment group but were not protected from a homologous
      intraperitoneal bacterial challenge. By contrast, treatment groups vaccinated
      with P. multocida outer membrane, formalin-killed P. multocida or a commercial
      vaccine were significantly protected from challenge. In vitro complement-mediated
      killing of P. multocida was observed in post-vaccination sera of outer membrane,
      formalin-killed P. multocida, and commercial vaccine-treatment groups, but not
      with sera from the Omp28-treatment group. In conclusion, although Omp28 is
      surface exposed and antigenic, it may not be a desirable immunogen for
      stimulating immunity to P. multocida.

PMID- 12052334
TI  - Diagnosis of footrot in goats: application of ELISA tests for response to
      antigens of Dichelobacter nodosus.
AB  - Goats are an important natural host for footrot and are infected with
      Dichelobacter nodosus that have virulence characteristics similar to those of
      sheep strains. However, the humoral response of goats to D. nodosus antigens and
      the possibility of a serological diagnosis of footrot in goats have not been
      studied. With the aim of evaluating a diagnostic ELISA test, we investigated the
      primary immune response of goats to experimental and natural infection, the
      memory response in recovered animals, and the transfer and persistence of
      colostral antibodies in kids. Footrot stimulated the goat's immune system and, as
      in sheep, under-running lesions were the primary stimulus for production of anti
      D. nodosus antibodies. The immune response could be detected in ELISA using
      either fimbrial or outer membrane protein (KSCN) antigens of D. nodosus. Antibody
      titres resulting from infection declined quickly after recovery and reached pre
      infection levels within 3-4 months. Previously affected animals, however, mounted
      a memory response when injected with purified D. nodosus antigens. Antibody
      levels attained after anamnestic challenge were correlated with the maximum
      levels attained during infection, and were therefore indicative of the infection
      status. Anti-D. nodosus antibodies were also transferred to kids via colostrum,
      but these antibodies did not persist and therefore were unlikely to interfere
      with the diagnostic ELISA after 3 months of age. Though these ELISA tests were
      highly specific, their sensitivity was rather low. Therefore, they are only
      suitable for a herd diagnosis of footrot in goats and are dependent on the
      development of advanced under-running infections in a proportion of affected
      goats.

PMID- 12052335
TI  - Prevalence of Escherichia coli O157:H7 prophage-like sequences among German
      Salmonella enterica serotype Typhimurium phage types and their use in detection
      of phage type DT104 by the polymerase chain reaction.
AB  - A 1.6kb DNA fragment identified by random amplifiable polymorphic DNA
      differentiation (RAPD) from a Salmonella enterica serotype Typhimurium phage type
      DT104 isolate was used to investigate the prevalence of the region in 160 DT104
      isolates, 83 other epidemiological important S. Typhimurium phage types and 20
      strains selected from 17 other Salmonella serotypes. PCR screening tests using
      two different primer-sets derived from the RAPD fragment's nucleotide sequence
      showed that 76% of the 160 DT104 isolates investigated, including subtypes
      DT104A, DT104B, DT104B low, DT104H and DT104L, reacted positively. High
      sensitivity was shown for DT104 strains expressing at least the penta-resistance
      pattern ACSSuT (97% of 104 strains tested). DT104 susceptible strains showed only
      a sensitivity of 35% (17 strains tested). In contrast, 83% of the 83 strains from
      the other S. Typhimurium phage types reacted negatively. Strains from five out of
      the 17 other serotypes showed a positive signal with one primer-set. The other
      primer-set exhibited only a positive reaction with one S. Dublin isolate. The
      analysis of a 2415bp extended sequence revealed homologies to genes encoded by
      Escherichia coli O157:H7 prophages, suggesting that the described region contains
      genes of a prophage specific for DT104 and related phage types.

PMID- 12052336
TI  - Effect of fermented feed on shedding of Enterobacteriaceae by fattening pigs.
AB  - Epidemiological studies showed that the use of fermented feed could significantly
      reduce Salmonella prevalence in pigs compared to the use of normal feed.
      Experimental challenge experiments with Salmonella have however never been
      conducted to reveal the efficacy of fermented feed in reducing Salmonella
      shedding and/or reducing the number of Salmonella-positive pigs. A longitudinal
      study was conducted to measure the effect of fermented feed, in particular of its
      components lactic acid and Lactobacillus plantarum, on gastrointestinal bacterial
      ecology (Salmonella, Enterobacteriaceae, lactobacilli, volatile fatty acids
      (VFAs), pH). Seeder pigs were used as a mode for Salmonella transmission within a
      pig herd. Bacteriological measurements were performed in faeces of the pigs. The
      results showed that fermented feed affected/reduced the Enterobacteriaceae
      population in faeces of the pigs. No differences were found in the number of
      positive pigs infected or in the number of shedding with Salmonella serovar
      Typhimurium fed fermented feed and between the normal feed group. S. serovar
      Goldcoast could not establish an infection in the seeder pigs in the fermented
      feed group as well as in the normal feed group. The pH of the faeces in the
      fermented feed groups was significantly higher than the pH of the faeces of the
      normal feed groups. The role of the undissociated form of the faecal VFAs on the
      significantly lower Enterobacteriaceae number in faeces of the pigs of the
      fermented feed groups could not be demonstrated because of the significant higher
      pH in the faeces of the pigs fed fermented feed.

PMID- 12052337
TI  - Characterization of mitogen-stimulated porcine lymphocytes using a stable
      fluorescent dye (PKH2) and multicolor flow cytometry.
AB  - Stimulation of lymphocyte proliferation using mitogens or specific antigens is a
      method that is used frequently to assess immune responsiveness. While useful,
      lymphocyte blastogenesis, or [3H]-thymidine incorporation, provides little
      information regarding the response of specific subsets to the stimulant. Here, we
      report that the fluorescent cell membrane probe, PKH2, is a useful tool for
      measuring the proliferation of porcine lymphocyte subpopulations by utilizing
      multicolor flow cytometry. For this study, mitogen-induced proliferation of
      porcine peripheral blood mononuclear cells (PBMCs) was measured using [3H]
      thymidine incorporation as well as a flow cytometric-based proliferation assay.
      From the [3H]-thymidine incorporation data alone, it was observed that PBMC
      stimulated with either concanavalin A (Con A), phytohemagglutinin (PHA) or
      pokeweed mitogen (PWM) demonstrated greater proliferation on day 3 than on day 5
      of culture. Using the PKH dye and flow cytometric analysis, the responsiveness of
      specific lymphocyte subsets to mitogen stimulation was detected. The predominant
      subsets of porcine lymphocytes responding to Con A or PHA stimulation were
      CD4(+)CD8(+), CD4(-)CD8alpha(hi), CD4(-)CD8alpha(lo) and gammadelta TCR(+) cells.
      PWM stimulation induced responses by CD4(+)CD8(+), CD4CD8alpha(hi) but not by
      CD4(-)CD8alpha(lo) or gammadelta TCR(+) cells. Con A stimulation resulted in a
      sustained proliferation of CD8alpha(hi) cells over the 5-day period while PHA
      stimulation resulted in proliferation that peaked within the first 3 days. Little
      or no proliferative responses were detected within the IgM(+) population (e.g. B
      cells). This is the first study to define the contribution of individual
      lymphocyte subsets to mitogen-induced proliferation of porcine PBMCs.

PMID- 12052339
TI  - Effect of tumor infiltrating lymphocytes on the expression of MHC molecules in
      canine transmissible venereal tumor cells.
AB  - Canine transmissible venereal tumor (CTVT) can be allo-transplanted across major
      histocompatibility complex barriers. The expression of MHC molecules is usually
      low in the progression (P) stage and then greatly increases during tumor
      regression (R). We investigated the effects of tumor infiltrating lymphocytes
      (TIL) on the expression of MHC molecules of CTVT cells. Isolated, viable CTVT
      cells were inoculated at each of 12 sites (1 x 10(8) CTVT cells per site) on the
      back of six, mixed-breed dogs. Tumor masses were collected every 2-3 weeks and
      prepared for histopathologic, immunocytochemistry, flow cytometry and
      immunoblotting studies. The level of MHC expression on tumor cells from different
      stages of growth was measured. Initially, expression of MHC I and II molecules in
      P phase CTVT was low. Twelve weeks post-inoculation (PI), expression increased
      dramatically and it continued to increase during R phase. Tumor growth slowed
      after 12 weeks PI and tumors entered R phase around 17 weeks PI. We hypothesize
      that CTVT evades host immunosurveillance and grows progressively for 12 weeks,
      when it becomes vulnerable and subject to the host's anti-tumor immune responses.
      We further demonstrated that R phase, but not P phase, TIL were closely
      associated with the over-expression of MHC I and II molecules by CTVT cells. The
      number and proportion of TIL were higher in R phase tumors. Supernatants, from R
      phase co-cultures (CTVT+TIL) and TIL only, promoted MHC I and II expression on P
      phase CTVT cells. After culturing alone for 1 month, expression of MHC classes I
      and II molecules in R phase CTVT cells decreased to the level of P phase CTVT
      cells. However, the above-mentioned supernatants restored their expression of MHC
      I and II molecules. In contrast, supernatants from P phase TIL or CTVT cells
      increased expression slightly or had no effect. Therefore, TIL, not CTVT cells,
      produce the effective substance (s) to promote the expression of MHC molecules by
      the tumor cells. Heat treated supernatant was unable to promote the expression of
      MHC I and II molecules by CTVT cells. In conclusion, TIL isolated from R phase
      CTVT secreted a heat-sensitive, soluble substance(s) that triggered over
      expression of MHC I and II after 12 weeks PI. This caused the tumor to enter R
      phase and helped stop CTVT growth. Our findings will facilitate the understanding
      and further investigation of the mechanisms that initiate host immune
      surveillance against tumors.

PMID- 12052338
TI  - Lipopolysaccharide induces inflammatory cytokines in the pig amnion.
AB  - Inflammatory mediators that are induced by gram-negative bacteria in the course
      of intrauterine infections threaten successful pregnancy. To compare the effect
      of two different routes of cytokine induction, bacterial lipopolysaccharide (LPS)
      was administered in vivo either into the cord vein or into the amniotic cavity of
      pig fetuses in the second half of gestation for 20 h and cytokines were detected
      in the amnion.Tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8)
      were induced in the amniotic epithelium after intra-amniotic but not after intra
      venous administration of LPS. The presence of IL-8 was confirmed by RT-PCR. In
      contrast, transforming growth factor-beta1 (TGF-beta1) was expressed
      constitutively and was found in all samples of the amniotic epithelium. Amniotic
      fluid contained only minute levels of TNF-alpha. IL-8 levels in amniotic fluid
      increased after the treatment with LPS and the highest IL-8 levels were found in
      dead LPS-treated fetuses.

PMID- 12052340
TI  - The DNA vaccine vector pcDNA3 induces IFN-alpha production in pigs.
AB  - The cytokine inducing capacity of the vaccine vector pcDNA3, a methylated form of
      the plasmid, and pcDNA3 encoding porcine interleukin (IL)-6 or
      granulocyte/macrophage colony-stimulating factor (GM-CSF) was studied in pigs,
      using a model with tissue chambers implanted subcutaneously. The production of
      interferon (IFN)-alpha, IFN-gamma, IL-6 and GM-CSF was studied at local (tissue
      chamber fluid (TCF)) and systemic (serum) levels during 3 days post-injection.
      All forms of the plasmid, except the methylated, induced a transient local
      production of IFN-alpha but no plasmid-induced production of IFN-gamma, GM-CSF or
      IL-6 could be detected after injection of the plasmids. The IFN-alpha response
      increased markedly at repeated injections of pcDNA3. This IFN-alpha inducing
      capacity of the plasmid is likely to affect immune responses at DNA vaccination
      of pigs.

PMID- 12052341
TI  - Development of a canine trypsin-like immunoreactivity assay system using
      monoclonal antibodies.
AB  - The radioimmunoassay (RIA) for trypsin-like immunoreactivity (TLI) is one of the
      most sensitive and specific tests for detecting exocrine pancreatic insufficiency
      (EPI). An abnormally low serum TLI concentration (<2.5 ng/ml) indicates end-stage
      EPI. Although RIA methods can be used to detect canine serum TLI, these
      procedures are beyond the capabilities of most veterinary clinics and general
      laboratories. Using monoclonal antibodies (mAbs), we developed an enzyme-linked
      immunosorbent assay (ELISA) for canine TLI and incorporated it into an
      immunochromatographic test (ICT) for the diagnosis of EPI. The ELISA was linear
      over TLI concentrations of 1-100 ng/ml. Levels of intra-assay coefficients of
      variance (CVs) were 1.8-6.1%, inter-assay CVs were 5.1-9.8%, and the recovery of
      TLI added to two samples of canine serum ranged from 89 to 111 and 93 to 108%,
      respectively. Good correlation (correlation coefficient, 0.974) occurred between
      the TLI values obtained by the ELISA method and those by RIA from 56 clinical
      samples. Serum TLI values in clinically healthy dogs ranged from 7.8 to 29.2
      ng/ml by ELISA, and those from dogs with EPI were 0.0-0.6 ng/ml. The values were
      0.0-287.4 ng/ml for dogs with pancreatitis, and those from dogs with
      gastrointestinal disease were 5.5-58.9 ng/ml. The only statistically significant
      difference (P<0.01) occurred between the TLI level of healthy dogs and those with
      EPI. The ICT kit showed high reproducibility, and the TLI values yielding
      negative results differed significantly (P<0.01) from those returning positive
      results. The ICT kit yielded negative results (indicating EPI) from clinical
      serum samples with TLI concentrations of 0.0-4.1 ng/ml by ELISA. Both the ELISA
      and ICT kit are useful tools in the diagnosis of canine EPI.

PMID- 12052342
TI  - Changes in the leucocyte subpopulations of the palatine tonsillar crypt
      epithelium of pigs in response to Streptococcus suis type 2 infection.
AB  - The tonsils are portal of entry and a site of multiplication and persistence for
      a variety of pathogens, including Streptococcus suis (S. suis), which is a common
      cause of meningitis, septicemia and arthritis in pigs. Understanding the early
      changes that occur in the first barrier of the tonsil, i.e. the crypt epithelium,
      in response to S. suis infection is critical in clarifying the pathogenesis of
      this disease and for the future development of efficient methods of mucosal
      vaccination. In this study, we investigated the early changes, from 18 to 72 h,
      that occur in leucocyte subpopulations of the crypt epithelium of the palatine
      tonsils of 3-week-old pigs in response to S. suis type 2 infection. Monoclonal
      antibodies against leucocyte markers CD3, CD4, CD8, gammadelta T cell receptor,
      lambda-immunoglobulin light-chain, myeloid cells, and major histocompatibility
      complex class II molecule (MHC-II) were used in an avidin-biotin immunoperoxidase
      technique. An increase in the number of lambda-immunoglobulin light-chain
      positive cells (B cell subset) was noticed in crypts of S. suis-infected animals
      from 18 h after infection onwards. This increase was significant at 18 and 48 h
      after infection. The number of CD4 and CD8 cells was greater from 18 h onwards,
      with a significant increase at 24 and 72 h post-infection. No significant
      difference in numbers of CD3, gammadelta T cell receptor and MHC-II positive
      cells was detected in the crypts of infected animals compared to controls.
      Macrophages, neutrophils and crypt epithelial cells stained positively with the
      myeloid marker, and the area of crypt epithelium positive for this marker was
      increased in the crypts of infected animals, with a significant difference
      detected at 24 and 72 h after infection. These results suggest that there is
      participation of the innate immunity in the early phase of S. suis infection,
      represented by neutrophils, macrophages and likely epithelial cells, and that
      there is a potential for the initiation of both humoral and cellular responses
      against S. suis within the crypt epithelium of the palatine tonsil.

PMID- 12052343
TI  - High level expression and purification of bioactive bovine interleukin-18 using a
      baculovirus system.
AB  - Bioactive recombinant bovine interleukin-18 (rboIL-18) was expressed using a
      baculovirus system. Normally, IL-18 is translated as a precursor form of a 24kDa
      polypeptide and processed by IL-1beta converting enzyme (ICE) to a mature
      bioactive form of 18kDa protein. Hence, to express active form IL-18, we
      constructed two recombinant baculoviruses containing boIL-18 and human ICE (hICE)
      genes, respectively, and superinfected these viruses into insect cells.
      Superinfection of both recombinant viruses into the cells resulted in the
      expression of a 24kDa precursor form and an 18kDa mature form detectable in the
      supernatant by immunoblotting using anti-porcine IL-18 antibody. Culture
      supernatant from the superinfected cells showed a synergistic effect with
      recombinant boIL-12 for production of interferon-gamma (IFN-gamma) in bovine
      peripheral mononuclear cells. By addition of histidine hexamer at the C-terminal
      of boIL-18, the mature IL-18 was purified. Bioactivity remained after
      purification.

PMID- 12052344
TI  - Detection of Mycobacterium bovis infection and production of interleukin-2 by in
      vitro stimulation of badger lymphocytes.
AB  - The Eurasian badger (Meles meles) is considered to be an important wildlife
      reservoir for Mycobacterium bovis infection of cattle in Ireland and in GB.
      However, rapid diagnosis of tuberculosis in live badgers has been constrained
      through a lack of suitable immuno-diagnostic reagents for detection of M. bovis
      infected animals. To date, there have been no reports of cytokine activity in
      badgers that might be associated with specific immune responses to M. bovis
      infection. In this study, nine badgers were removed from an area with a
      persistent tuberculosis problem in cattle herds and tuberculosis was confirmed in
      four of the animals by "post-mortem" examination and M. bovis culture. In
      preliminary investigations of interleukin-2 (IL-2) activity, we were able to
      demonstrate that lymphoblasts prepared from badger peripheral blood mononuclear
      cells (PBMCs) proliferated when cultured in the presence of human recombinant IL
      2 (HrIL-2). Supernatants derived from purified protein derivative of tuberculin
      (PPD-bovine) stimulated PBMC cultures also induced blastogenesis of badger
      derived lymphoblasts. The results demonstrate that badger lymphocytes are
      responsive to HrIL-2 and that PPD-bovine stimulation of badger PBMC results in
      production of bio-active IL-2.

PMID- 12052345
TI  - Glucocorticoid regulation of type 1 and type 2 cytokines in cultured porcine
      splenocytes.
AB  - Glucocorticoids are reported to bias cytokines to a Th2 phenotype. However, this
      dogma has been advanced largely from studies utilizing potent glucocorticoid
      analogs. The current study was conducted to revisit the issue of glucocorticoid
      modulation of Th1/Th2 cytokine production and evaluate migration inhibitory
      factor (MIF) mRNA expression in cultured pig splenocytes treated with
      physiologically relevant concentrations of cortisol (CORT). Dexamethasone (DEX)
      was included for comparison. In Experiment 1, DEX, at 150 and 300 nM, suppressed
      concanavalin (ConA)-stimulated IFNgamma at both 12 and 24 h in culture, and IL-10
      at 24h (P<0.05). Both 150 and 300 nM CORT suppressed IL-10 at 24 h (P<0.05), but
      neither concentration affected IFNgamma at 24 h. In Experiment 2, cells were
      cultured with a broader range of CORT for 48 h following ConA. Parallel cultures
      with identical treatments also were conducted in separate plates for evaluation
      of glucocorticoid regulation of MIF mRNA. IFNgamma was reduced by 300 nM DEX at
      12, 24, and 48 h (P<0.05), whereas 150 and 300 nM CORT blunted IFNgamma at 24 h
      (P<0.05), but not 48 h. ConA increased IL-2 (P<0.01), but none of the steroid
      treatments affected IL-2. At both 12 and 24 h, IL-10 was reduced by 300 nM DEX
      and by 150 and 300 nM CORT (P<0.05). ConA increased relative abundance of MIF
      mRNA (P<0.001), but no steroid treatment affected MIF mRNA. In Experiment 3,
      steroid additions were delayed by 24 h after ConA, and cytokine concentrations
      evaluated 48 h later. Again, separate cultures were used for determination of
      effect of treatments on MIF mRNA. None of the steroid treatments affected
      IFNgamma, but 300 nM DEX reduced IL-10 (P<0.05). All of the CORT treatments (75
      300 nM) reduced MIF mRNA (P<0.05), whereas DEX did not affect MIF mRNA in this
      experiment. The current experiments suggest that both DEX and high physiological
      concentrations of CORT can suppress both type 1 and type 2-like cytokines in
      cultured pig splenocytes. But, IL-10 was generally more sensitive to CORT
      suppression with increased time in culture than was IFNgamma. In addition, MIF
      mRNA could be suppressed by delayed addition of CORT to porcine splenocytes.
      Taken together, the data do not support the hypothesis that CORT directs the
      cytokine milieu toward a type 2 bias in cultured pig splenocytes.

PMID- 12052346
TI  - The influence of nonspecific immunostimulation of pregnant sows on the
      immunological value of colostrum.
AB  - The purpose of this experiment was to estimate the influence of nonspecific
      immunostimulation of pregnant sows on the immunological value of colostrum. The
      studies were done in the fall-winter season on 20 pregnant sows (Polish Landrace)
      divided into four groups, five animals each. The sows were clinically healthy and
      unvaccinated. Group I received isoprinosine, group II (TFX), group III (HMB), and
      group IV served a control. The immunostimulants were applicated 4-6 weeks before
      the expected date of delivery. The following parameters were determined in
      colostrum taken from sows after completed delivery: specific gravidity; total
      proteins, lysozyme activity, IgG level. It was found that the nonspecific
      immunostimulation of pregnant sows increased in colostrum the level of IgG, total
      protein content and lysozyme activity.

PMID- 12052348
TI  - Bacteria-degraders as the base of an amperometric biosensor for detection of
      anionic surfactants.
AB  - Several strains belonging to genera Pseudomonas and Achromobacter and
      characterized by the ability to degrade anionic surfactants were tested as
      potential bases of microbial biosensors for surfactant detection. For each strain
      the substrate specificity and stability of sensor signals were studied. The total
      amount of the substrates tested (including carbohydrates, alcohols, aromatics,
      organic acids, etc.) was equal to 60; the maximal signals were observed towards
      the anionic surfactants. The lower limit of detection for sodium dodecyl sulfate
      used as a model surfactant was in the field of 1 microM for all the strains. The
      created microbial biosensor model can extend the practical possibilities for
      rapid evaluation of surfactants in water media.

PMID- 12052347
TI  - Real-time polymerase chain reaction assays for leukocyte CD and cytokine mRNAs of
      the Eastern woodchuck (Marmota monax).
AB  - Real-time polymerase chain reaction (PCR) assays were developed for woodchuck
      leukocyte cluster of differentiation (CD) and cytokine mRNA expression. Plasmid
      DNA standards of each marker (CD3, CD4, CD8, IL-2, IFN-gamma, TNF-alpha, IL-4, IL
      10), and RNA standards from mitogen-stimulated woodchuck peripheral blood
      mononuclear cells (PBMCs) were used to validate and optimize the assays for
      TaqMan 7700 and iCycler PCR instruments. The complementary DNAs (cDNAs) produced
      by reverse transcription (RT) of RNA were quantified by real-time PCR against the
      plasmid DNA standards (6-8 log range) with detection of as few as 10-50 copies of
      amplicon cDNA per reaction. Analysis of unstimulated and concanavalin A
      stimulated woodchuck PBMC demonstrated increased CD and cytokine mRNA expression
      following mitogenic activation. A liver sample from a woodchuck hepatitis virus
      (WHV) infected woodchuck with histologically confirmed acute hepatitis had
      increased intrahepatic CD and cytokine mRNAs compared to liver from an uninfected
      control woodchuck. The real-time PCR assays were highly specific for the
      woodchuck markers in PBMC and liver samples and were equally applicable for use
      in alternate real-time PCR instrumentation. These assays will enable the high
      throughput analyses of mRNA markers during WHV infection, and thereby facilitate
      continued modelling of the immunopathogenesis and immunotherapy of human
      hepatitis B virus (HBV) infection.

PMID- 12052349
TI  - Calibration of a subcutaneous amperometric glucose sensor. Part 1. Effect of
      measurement uncertainties on the determination of sensor sensitivity and
      background current.
AB  - The calibration of a continuous glucose monitoring system, i.e. the
      transformation of the signal I(t) generated by the glucose sensor at time (t)
      into an estimation of glucose concentration G(t), represents a key issue. The two
      point calibration procedure consists of the determination of a sensor sensitivity
      S and of a background current I(o) by plotting two values of the sensor signal
      versus the concomitant blood glucose concentrations. The estimation of G(t) is
      subsequently given by G(t) = (I(t)-I(o))/S. A glucose sensor was implanted in the
      subcutaneous tissue of nine type 1 diabetic patients during 3 (n = 2) and 7 days
      (n = 7). For each individual trial, S and I(o) were determined by taking into
      account the values of two sets of sensor output and blood glucose concentration
      distant by at least 1 h, the procedure being repeated for each consecutive set of
      values. S and I(o) were found to be negatively correlated, the value of I(o)
      being sometimes negative. Theoretical analysis demonstrates that this phenomenon
      can be explained by the effect of measurement uncertainties on the determination
      of capillary glucose concentration and of sensor output.

PMID- 12052350
TI  - Calibration of a subcutaneous amperometric glucose sensor implanted for 7 days in
      diabetic patients. Part 2. Superiority of the one-point calibration method.
AB  - Calibration, i.e. the transformation in real time of the signal I(t) generated by
      the glucose sensor at time t into an estimation of glucose concentration G(t),
      represents a key issue for the development of a continuous glucose monitoring
      system. OBJECTIVE: To compare two calibration procedures. In the one-point
      calibration, which assumes that I(o) is negligible, S is simply determined as the
      ratio I/G, and G(t) = I(t)/S. The two-point calibration consists in the
      determination of a sensor sensitivity S and of a background current I(o) by
      plotting two values of the sensor signal versus the concomitant blood glucose
      concentrations. The subsequent estimation of G(t) is given by G(t) = (I(t)
      I(o))/S. RESEARCH DESIGN AND METHODS: A glucose sensor was implanted in the
      abdominal subcutaneous tissue of nine type 1 diabetic patients during 3 (n = 2)
      and 7 days (n = 7). The one-point calibration was performed a posteriori either
      once per day before breakfast, or twice per day before breakfast and dinner, or
      three times per day before each meal. The two-point calibration was performed
      each morning during breakfast. RESULTS: The percentages of points present in
      zones A and B of the Clarke Error Grid were significantly higher when the system
      was calibrated using the one-point calibration. Use of two one-point calibrations
      per day before meals was virtually as accurate as three one-point calibrations.
      CONCLUSION: This study demonstrates the feasibility of a simple method for
      calibrating a continuous glucose monitoring system.

PMID- 12052351
TI  - Optimisation of glass surfaces for optical immunosensors.
AB  - The surfaces of glass sensor chips were modified with dextran to generate a layer
      protecting the sensor surface from unspecific protein binding and also serving as
      a matrix for covalent protein immobilisation. Dextran was coupled to the glass
      surface in different concentrations either covalently on amino-functionalised
      glass chips or via biotin-avidin binding. Unspecific binding of BSA was monitored
      with the grating coupler system, and was increasingly suppressed with increasing
      dextran concentrations. Using a solution with 100 mg/ml carboxymethylated dextran
      decreased the signals to approximately 2% of those obtained at an untreated glass
      chip. Antibodies were successfully immobilised in the dextran and binding to the
      corresponding Cy5-labelled antigen was repeatedly monitored using a fluorescence
      sensor system (total internal reflection fluorescence (TIRF)).

PMID- 12052352
TI  - Optical biosensors for real-time measurement of analytes in blood plasma.
AB  - The preparation of assemblies consisting of multiple molecular layers of bovine
      serum albumin (BSA), monoclonal antibodies against horseradish peroxidase (anti
      HRP), and monoclonal antibodies against methotrexate (anti-MTT), as well as
      interaction of the assemblies with human blood plasma were observed using a
      grating coupler and Young interferometer (YI). The assemblies could be arranged
      according to decreasing amounts of nonspecific deposits bound irreversibly to
      them from blood plasma as follows-an adsorbed antibody monolayer saturated with
      adsorbed BSA, antibody multilayers linked with polycations, antibodies covalently
      immobilized on a BSA layer densely crosslinked with glutaraldehyde (GA), slightly
      crosslinked BSA double layer, slightly crosslinked antibody double layers. The
      occurrence of human serum albumin (HSA), human fibrinogen (Fg), IgG, and IgM in
      the plasma deposits was studied by binding the respective antibodies. IgG, IgM,
      and Fg were detected in plasma deposits on the immobilized assemblies while the
      composition of a plasma deposit on the unmodified sensor surface reflected
      roughly the plasma composition containing mainly adsorbed HSA and Fg. A
      crosslinked anti-HRP double layer was immobilized on a waveguiding branch of YI
      and a similar anti-MTT double layer was immobilized on the other branch. The
      sensor response to blood plasma was fairly decreased owing to a compensation of
      the respective optical changes in the two branches, in which a similar non
      specific adsorption took place. The addition of HRP or MTT to plasma induced
      specific responses of the corresponding branches.

PMID- 12052353
TI  - Immunosensor for the differentiation and detection of Salmonella species based on
      a quartz crystal microbalance.
AB  - Immunosensors based on the microgravimetric quartz crystal microbalance (QCM)
      technique have been developed for the detection of Salmonella species from
      serogroups A, B and D. Salmonella serogroup-specific murine monoclonal
      antibodies, respectively, raised against these serogroups were immobilized onto
      the silver electrodes of piezoelectric (PZ) crystals by cross-linkage via
      glutaraldehyde (GA) to the electrode surfaces pre-coated with thin
      polyethyleneimine (PEI) layer. The specific immunosensors developed gave
      responses in linear ranges from 10(5) to 5x10(8) cells per ml with no significant
      interference from other strains of Salmonella and Escherichia coli up to 10(8)
      cells per ml. They showed good repeatability and excellent linear range,
      achieving detection limits down to 10(4) cells per ml with ability to distinguish
      different strains of Salmonella. These biosensors exhibited an exquisite
      specificity evidenced by their ability to discriminate antigens, the structures
      of which differ only by the isomeric form of di-deoxyhexose. The antibody
      modified crystals showed no loss in activity over 4 days under storage at 4
      degrees C.

PMID- 12052354
TI  - A biohybrid system to interface peripheral nerves after traumatic lesions: design
      of a high channel sieve electrode.
AB  - Peripheral nerve lesions lead to nerve degeneration and flaccid paralysis. The
      first objective in functional rehabilitation of these diseases should be the
      preservation of the neuro-muscular junction by biological means and following
      functional electrical stimulation (FES) may restore some function of the
      paralyzed limb. The combination of biological cells and technical microdevices to
      biohybrid systems might become a new approach in neural prosthetics research to
      preserve skeletal muscle function. In this paper, a microdevice for a biohybrid
      system to interface peripheral nerves after traumatic lesions is presented. The
      development of the microprobe design and the fabrication technology is described
      and first experimental results are given and afterwards discussed. The technical
      microprobe is designed in a way that meets the most important technical
      requirements: adaptation to the distal nerve stump, suitability to combine the
      microstructure with a containment for cells, and integrated microelectrodes as
      information transducers for cell stimulation and monitoring. Micromachining
      technologies were applied to fabricate a polyimide-based sieve-like microprobe
      with 19 substrate-integrated ring electrodes and a distributed counter electrode.
      Monolithic integration of fixation flaps and a three-dimensional shaping
      technology led to a device that might be adapted to nerve stumps with
      neurosurgical sutures in the epineurium. First experimental results of the
      durability of the shaping technology and electrochemical electrode properties
      were investigated. The three-dimensional shape remained quite stable after
      sterilization in an autoclave and chronic implantation. Electrode impedance was
      below 200 kOmega at 1 kHz which ought to permit recording of signals from nerves
      sprouting through the sieve holes.

PMID- 12052355
TI  - Immobilization of urease on poly(N-vinyl carbazole)/stearic acid Langmuir
      Blodgett films for application to urea biosensor.
AB  - Urease was immobilized in mixed monolayers of poly(N-vinyl carbazole) (PNVK) and
      stearic acid (SA) formed at an air-water interface. The monolayers were
      transferred onto indium-tin-oxide (ITO) coated glass plates using Langmuir
      Blodgett (LB) film deposition technique. Urease immobilized on PNVK/SA LB films,
      characterized using FTIR and UV-visible spectroscopy, was found to exhibit
      increased stability over a wide pH (6.5-8.5) and temperature (25-50 degrees C)
      range. Potentiometric measurements on these urease electrodes were carried out
      using an ammonium ion analyzer. Two values for K(m)(app) were obtained at lower
      and higher concentrations of substrate urea.

PMID- 12052356
TI  - Sensitivity studies for specific binding reactions using the biotin/streptavidin
      system by evanescent optical methods.
AB  - The combination of various evanescent optical methods such as surface plasmon
      spectroscopy, waveguide mode spectroscopy and an integrated optical Mach-Zehnder
      interferometer are used to characterize biotinylated self-assembled monolayers as
      well as the binding of streptavidin to these labels. The aim of designing a
      highly specific and sensitive, re-usable affinity sensor for antigens on the
      basis of an integrated optical Mach-Zehnder interferometer is based on a proper
      understanding of the characteristics of the entire binding matrix architecture.
      Therefore, a variety of biotin-derivatives immobilized in a monolayer are
      investigated with respect to their affinity to streptavidin and the possibility
      to remove the steptavidin layer specifically. The density of the streptavidin
      layer as well as the optical constants of the involved molecules are measured.
      Finally the integrated optical Mach-Zehnder interferometer is tested with respect
      to the sensitivity to an antigen-antibody binding reaction. An attempt to further
      increase the sensitivity by simultaneous detection of a fluorescence signal
      failed due to bleaching effects.

PMID- 12052357
TI  - Differentiating the orientations of photosynthetic reaction centers on Au
      electrodes linked by different bifunctional reagents.
AB  - The photosynthetic reaction center (RC) composite film was fabricated by self
      assembled monolayers (SAMs) on the Au electrode with two different bifunctional
      reagents, 4-aminothiophenol (ATP) and 2-mercaptoethylamine (MEA), respectively.
      The square wave voltametry (SWV), bulk electrolysis and photocurrent test were
      employed for characterizing the composite film. The dramatic different
      electrochemical characteristics were observed for the two types of films, which
      strongly suggested an orientational difference for RC arising from the structural
      difference between the two bifunctional reagents. For RC-MEA film, three redox
      peaks which implying electron transfer (ET) between the primary donor (P) and the
      bacteriopheophytin (Bphe) were observed. While for RC-ATP film, two redox peaks
      implying ET between the nonheme iron and the primary quinone (Q(A)) were
      observed. The ET behavior driven by electric field also supported the result that
      the RC could be linked to the electrode at different sites. The site-specific
      immobilization approach reported here supplies a method to differentiate the
      protein orientation.

PMID- 12052358
TI  - The discrimination of stenosed carotid bifurcation models with smooth and
      irregular plaque surface. Part I. Laser and ultrasonic Doppler flow studies.
AB  - Irregular carotid lesion surface is considered as a factor increasing the risk of
      the cerebral embolism. The objective of the study was to investigate the
      possibility to distinguish models of stenosed carotid bifurcation with lesion
      irregularity on the basis of the properties of flow velocity distributions. Two
      groups of elastic replicas of carotid bifurcations with different stenosis degree
      were investigated. Each group consisted of three models with different severity
      of plaque surface irregularity and one with smooth wall. Velocity data were
      collected using a one-component laser Doppler anemometer (LDA) system and a
      pulsed Doppler flowmeter. The LDA velocity distributions and Doppler spectral
      broadening index, turbulence intensity index and coefficient of skewness were
      analysed. The lesion irregularity resulted in change of the size and/or shape of
      reversed/reduced flow areas and of the position of the jet with respect to those
      observed in a smooth wall model. The flow features observed in the ultrasonic
      Doppler spectra were generally coherent with the axial LDA velocity
      distributions. Doppler spectral parameters demonstrated different sensitivities
      to the severity of the wall irregularity, however, the complexity of curves of
      these indices versus time did not allow to draw decisive conclusions and implied
      use of a more sensitive tool of analysis.

PMID- 12052359
TI  - The discrimination of stenosed carotid bifurcation models with smooth and
      irregular plaque surface. Part II. The multivariate statistical analysis of
      ultrasonic Doppler velocity data.
AB  - According to the conclusion of the first part of the paper the Doppler spectral
      indices were analyzed in a detailed manner to provide a means to differentiate
      bifurcation models with different irregularities. Autoregressive (AR) models
      using the Akaike FPE criterion were fitted to the curves of the spectral
      broadening index, turbulence intensity index and coefficient of symmetry. These
      curves were also submitted to the data reduction significant point extraction
      algorithm. The multivariate discriminant analysis was performed on parameter
      vectors containing coefficients of AR models, data reduction rate and data
      reduction error. The discriminant analysis allowed distinguishing models with the
      same degree of stenosis and different plaque surface characteristics on the basis
      of these vectors. The highest discrimination efficiency was observed for
      parameter vectors obtained from TBI and SKEW curves. The efficiency of
      discrimination was slightly higher for more severely stenosed models.

PMID- 12052360
TI  - Measurement of ejection fraction with standard thermodilution catheters.
AB  - Right ventricle ejection fraction (RVEF) is clinically used to evaluate right
      ventricular function. The thermodilution method can be modified to estimate the
      RVEF. However, this method requires a thermistor with a fast time response in
      order to yield correct estimates. Digital signal processing techniques that were
      developed in previous works, allow the use of industry-standard slow time
      response thermistors for the measurement EF. However, these algorithms were not
      automated, and the works did not present a complete evaluation of the method's
      performance. This article presents a modified automated version of these
      algorithms, and uses numerical and in vitro simulations to test their
      performance. In the simulations, the measured ejection fraction was compared to
      the true ejection fraction. RVEFs ranging from 0.20 to 0.80 were tested for heart
      rates ranging from 30 to 120 heart beats per min. Statistical analysis of data
      showed that the new method presents an improved performance.

PMID- 12052361
TI  - Optimizing the biomechanical compatibility of orthopedic screws for bone fracture
      fixation.
AB  - Progressive loosening of bone fixation screws is a well-documented phenomenon,
      induced by stress shielding and subsequent adaptive bone remodeling which results
      in bone loss around the screw. A set of two-dimensional computational (finite
      element) models was developed in order to test the effect of various engineering
      designs of fixation screws on the predicted screw-bone stress transfer, and
      consequently, on the biomechanical conditions for osteosynthesis. A dimensionless
      set of stress-transfer parameters (STP) was developed to quantify the screw-bone
      load sharing, enabling a convenient rating to be given of the biomechanical
      compatibility of practically any given screw design according to the nature of
      the simulated mechanical interaction. The results indicated that newly proposed
      screw designs, i.e. a "graded-stiffness" composite screw with a reduced-stiffness
      titanium core and outer polymeric threads and an "active-compression" hollow
      screw which generates compressive stresses on the surrounding bone, are expected
      to provide significantly better biomechanical performances in terms of the STP
      criteria, compared with conservative screw designs. Accordingly, the present work
      demonstrates that finite element computer simulations can be used as a powerful
      tool for design and evaluation of bone screws, including geometrical features,
      material characteristics and even coatings.

PMID- 12052362
TI  - Automatic recognition of alertness and drowsiness from EEG by an artificial
      neural network.
AB  - We present a novel method for classifying alert vs drowsy states from 1 s long
      sequences of full spectrum EEG recordings in an arbitrary subject. This novel
      method uses time series of interhemispheric and intrahemispheric cross spectral
      densities of full spectrum EEG as the input to an artificial neural network (ANN)
      with two discrete outputs: drowsy and alert. The experimental data were collected
      from 17 subjects. Two experts in EEG interpretation visually inspected the data
      and provided the necessary expertise for the training of an ANN. We selected the
      following three ANNs as potential candidates: (1) the linear network with Widrow
      Hoff (WH) algorithm; (2) the non-linear ANN with the Levenberg-Marquardt (LM)
      rule; and (3) the Learning Vector Quantization (LVQ) neural network. We showed
      that the LVQ neural network gives the best classification compared with the
      linear network that uses WH algorithm (the worst), and the non-linear network
      trained with the LM rule. Classification properties of LVQ were validated using
      the data recorded in 12 healthy volunteer subjects, yet whose EEG recordings have
      not been used for the training of the ANN. The statistics were used as a measure
      of potential applicability of the LVQ: the t-distribution showed that matching
      between the human assessment and the network output was 94.37+/-1.95%. This
      result suggests that the automatic recognition algorithm is applicable for
      distinguishing between alert and drowsy state in recordings that have not been
      used for the training.

PMID- 12052363
TI  - Electret-thermal analysis of blood.
AB  - The thermally stimulated discharge (TSD) method, intended for the analysis of
      charged dielectrics, was used for human blood research. Above-room-temperature
      TSD spectra of blood consist of three peaks. There are indications that the low
      temperature peak (40-50 degrees C) corresponds to the thermally stimulated
      destruction of hydrate shells surrounding blood components while the mid
      temperature peak (70-90 degrees C) is related to thermal denaturation of blood
      proteins. The intensive high-temperature peak (105-120 degrees C) is observed
      when a phase transition of blood, accompanied by the formation of a firm dry film
      of blood, occurs. The position of the high-temperature peak depends on the blood
      group. Data is discussed which suggests that the spontaneous "quasi-electret
      effect" of blood relates to the character of the biochemical processes taking
      place in human organisms. The TSD method might be used as simple and informative
      means of diagnostics in cooperation with medical and physical investigations.

PMID- 12052364
TI  - The device and algorithm for estimation of the mechanoemisson chaos in blood of
      patients with gastric cancer.
AB  - The mechanoemission (ME) of blood is developed as a result of mechanochemical
      activation of a sample which is layered onto chromatographic paper. This paper
      describes computer-controlled device, aimed for generation, detection and
      analysis of ME data in the blood of the persons investigated. The original
      algorithm for estimation of ME chaos in blood is developed. For gastric cancer
      patients an increase of ME chaos is observed in comparison with healthy
      individuals and patients with inflammation of gastric mucosa. The concept of
      deterministic chaos is biohierarchical for the host of a cancer patient. In the
      light of this we have calculated that spatial chaos for gastric cancer patients
      is also increased in the geometrical structure of tumor cells and magnetic
      resonance imaging of the stomach. The concept of deterministic chaos may find an
      application in the development of new multi-computer organizations for medical
      diagnostic equipment.

PMID- 12052365
TI  - Survey: use of skin substitute materials in UK burn treatment centres.

PMID- 12052366
TI  - The effects of inhaled nitric oxide on the levels of cGMP plasma and lung tissue
      in a canine model of smoke inhalation injury.
AB  - The effects of inhaled nitric oxide (NO) on pulmonary hypertension and their
      mechanisms were studied in a canine model of smoke inhalation injury. Twenty-one
      dogs were randomly divided into three groups: four dogs constituted the normal
      control group, eight dogs subjected to smoke inhalation followed by O(2)
      inhalation (FiO(2)=0.45) constituted the injury control group, and nine dogs
      inhaling a mixture of O(2) and 45ppm nitric oxide after smoke exposure served as
      the treatment group. The levels of cyclic guanosine monophosphate (cGMP) in
      arterial plasma of the treatment group were higher than that of the control group
      at 5, 8, and 12h after smoke exposure, while the levels of cGMP in lung tissue
      were also significantly higher compared with that of the control group (P<0.01).
      The levels of cGMP of injury control group were decreased significantly compared
      with normal controls (P<0.05). Pulmonary vasoconstriction following smoke
      inhalation was significantly attenuated by inhalation of NO (P<0.05), which
      exerted no apparent effect on the systemic circulation (P>0.05). Inhalation of NO
      may lower pulmonary hypertension induced by smoke inhalation injury in dogs. The
      selective effect of NO on pulmonary circulation may be attributed to an increase
      in level of cGMP in smooth muscle cells of the lung tissue after inhalation of
      NO.

PMID- 12052367
TI  - Expression of heme oxygenase-1 in the lung and liver tissues in a rat model of
      burns.
AB  - To investigate the functional significance of heme oxygenase (HO)-1 as having
      anti-oxidant activity in burns, a rat model of 30% burns was prepared, and the
      lungs and livers were extirpated for immunohistological examination (indirect
      immunoenzyme techniques). Plasma TNF-alpha levels were significantly higher in
      the burn group than in the control group, but there was no significant difference
      in total bilirubin levels between the groups. HO-1 expression was found
      histologically in the perivascular cells of the lung and liver. It was also
      found, though only at low levels, in liver parenchymal cells. These results
      suggest that HO-1 is expressed in the lung and liver tissues in a rat model of
      burns.

PMID- 12052368
TI  - The effect of calcitonin and growth hormone on urinary deoxypyridinoline levels
      in burned patients.
AB  - Reduced bone formation and bone loss have been documented in patients following
      burn injury. Urinary deoxypyridinoline (DPD) is accepted as a marker of collagen
      breakdown activity. Because calcitonin (CT) diminishes bone resorption and growth
      hormone (GH) increases bone formation and density in GH-deficient patients, we
      studied the short-term effects of CT and GH on urinary DPD levels in burned
      patients. In 30 patients with severe burns, urinary DPD levels were investigated
      for 3 days following hospitalisation. Then the patients were divided into 3
      groups of 10. In the CT group, CT 100U was injected subcutaneously daily for 5
      days. In the GH group, GH 0.1mg/kg was injected subcutaneously three times in a
      week. In the control group, isotonic saline solution 0.1mg/kg was injected
      subcutaneously three times in a week. In all groups, following the last dose of
      the agents, urinary DPD levels were investigated for 3 days again. Mean burn size
      and age were not significantly different between the groups. Urinary DPD level
      obtained in the early period was 16.5 +/- 3.1nM in the CT group, 10.4 +/- 5.3nM
      in the GH group and 18.6 +/- 2.7nM in the control group. There were no
      statistical differences among the groups (P > 0.5, for all). Urinary DPD level
      obtained in the late period was 4.5 +/- 1.0nM in the CT group, 14.4 +/- 5.9nM in
      the GH group and 36.6 +/- 2.1nM in the control group. The differences between the
      CT group and control group, the CT group and GH group and the GH group and
      control group were statistically significant (P < 0.001, P < 0.01, P < 0.01,
      respectively). In the comparison of early and late urinary DPD levels, a
      significant decrease was only obtained in the CT group (P < 0.001, Z:6.5). In the
      other 2 groups, DPD levels increased in the late period. We concluded that GH is
      not effective in decreasing urinary DPD levels. On the contrary, CT was found to
      very effective in decreasing urinary DPD levels. This decrease in urinary DPD
      levels may be associated with diminished bone loss

PMID- 12052369
TI  - Downregulation of glucocorticoid receptors of liver cytosols and the role of the
      inflammatory cytokines in pathological stress in scalded rats.
AB  - Preliminary experiments indicated that target cells were resistant to
      glucocorticoid (GC) after pathological stress. This study was designed to
      investigate the alterations in plasma corticosterone level and GC receptor (GR)
      of liver cytosols, to assess the relative inflammatory cytokines contribution to
      GC resistant, and to observe the action of alpha-melanocyte-stimulating hormone
      (alpha-MSH) on the potential implications of glucocorticord regulatory effects in
      burned rats. Male Wistar rats (weight range, 180-200g) received a 35% total body
      surface area immersion scald and were randomly divided to receive either tumor
      necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), polyclonal
      antibody (pAb), alpha-MSH, Ac-D-Lys-L-Pro-D-Val (KPV peptide), or saline
      (control). The binding capacity (Rt) of the steroid-binding sites was measured by
      radioligand binding assay, using [3H]dexamethasone as the ligand. We examined
      plasma levels of IL-1beta, TNFalpha, IL-10, and corticosterone following scald
      challenge in rats. The Rt of GR (208.45+/-30.78fmol/mg of protein) in hepatic
      cytosol in rats, 12h later the scald was significantly lower than that (306.71+/
      27.96fmol/mg of protein) of the control group (P<0.01). The injections of anti
      rat TNFalpha (257.80+/-12.82fmol/mg of protein), IL-1beta antibody (254.46+/
      21.21fmol/mg of protein), alpha-melanocyte-stimulating hormone (278.32+/
      7.76fmol/mg of protein) and KPV peptide (263.46+/-17.46fmol/mg of protein) might
      prevent the Rt of GR from decreasing in hepatic cytosols of rats with scald,
      respectively (all of P<0.05) in vivo. Scald-induced robust increases in plasma IL
      1beta (214.08+/-27.25pg/ml), TNFalpha (111.18+/-23.97pg/ml), IL-10 (177.50+/
      15.79pg/ml) and corticosterone (2680+/-443.23ng/ml) levels after 12h. The
      administration of TNFalpha, IL-1beta pAb, alpha-MSH and KPV might attenuate these
      increases. These studies suggest that pro-inflammatory cytokines are involved in
      downregulation of GRs and thus alpha-MSH and KPV might increase the level of GR
      in rats with immersion scald.

PMID- 12052370
TI  - Ventral burn in rats: an experimental model for intravital microscopic study of
      microcirculation.
AB  - A novel technique of application of controlled ventral scald burn to rodent,
      whose back is inaccessible because of preburn preparation, is described. Boiling
      water is applied across a polyethylene membrane that partially envelops the
      subject. The technique is simple, economical, reproducible and allows intravital
      microscopic study of microcirculation in a remote muscular bed before and after
      burn injury.

PMID- 12052371
TI  - Impairment of splenic B and T lymphocytes in the early period after severe
      thermal injury: immunohistochemical and electron microscopic analysis.
AB  - Immunocompetent cells, such as lymphocytes and macrophages are easily damaged
      after severe thermal injury. In the present study, we investigated structural
      changes in splenic lymphocytes in the early period after a full skin thickness
      burn of 30% of the body surface area in rats. At 2h after thermal injury,
      numerous B lymphocytes had accumulated in the markedly expanded marginal zone of
      the splenic white pulp. Electron microscopy showed a small number of apoptotic
      cells in the marginal zone of the white pulp. After 5h, B lymphocytes in the
      marginal zone as well as in the lymphoid sheath and follicles were markedly
      decreased in number with an increase of tingible bodies and tingible body
      macrophages. The number of apoptotic cells had increased not only in the marginal
      zone, but also in the lymphoid sheath and follicles. After 12h, the splenic white
      pulp became atrophic with the appearance of a small number of large blastic cells
      and mitotic figures. After 24h, the splenic white pulp was still atrophic with a
      decrease in the number of lymphocytes, especially B lymphocytes. On the other
      hand, the large blastic cells and mitotic figures increased in number. Apoptotic
      cells decreased in number in the white pulp. After 48h, the lymph follicles were
      slightly enlarged and a small germinal centre occasionally appeared. A small
      number of T lymphocytes were observed in the splenic white pulp of the normal
      rats. However, the T lymphocytes almost disappeared shortly after thermal injury.
      A recovery in T cell number was observed only after 48h. These findings indicate
      that severe impairment of both B and T lymphocytes, circulating and in the
      lymphoid organs, occurs shortly after thermal injury and continues for several
      days. This severe damage to the lymphocytes is considered to be closely related
      to severe immune suppression after thermal injury.

PMID- 12052372
TI  - Frequency of Pseudomonas aeruginosa serotypes in burn wound infections and their
      resistance to antibiotics.
AB  - Pseudomonas aeruginosa plays a prominent role as an etiological agent involved in
      serious infections in burned patients. In this study P. aeruginosa infections
      were analyzed at the Motahari Burn Center in Tehran (from 22 December 1998 to
      April 1999) to estimate their frequency, antibiotic susceptibility and serotypes.
      One hundred and eighty-four positive cultures and 205 bacterial strains were
      isolated among swabs or biopsy specimens during the study period. Pseudomonas was
      found to be the most common (57%) followed by Acinetobacter (17%), Escherichia
      coli (12%), Staphylococcus aureus (8%) and other organisms (6%). The frequency of
      P. aeruginosa resistance to gentamicin, ceftizoxime, carbenicillin, cephalothin
      and ceftazidime was over 90%. The antibiotics to which P. aeruginosa was most
      sensitive were amikacin and tetracyclin. The "O" serotypes isolated from the 117
      Pseudomona aeroginosa isolates were serotypes O:2, O:5, O:6, O:8, O:11, O:12 and
      O:16. The most common serotype was O:6 (20/17%) followed by O:11 (18/15%) and O:5
      (14/12%). The serotype most resistant was O:16 (8%) and the most sensitive was
      O:8 (2%). Since treatment of infection with available antibiotics according to
      the results attained proved to be difficult, prevention of infection in the
      burned patients is considered as an appropriate means of conquering overcoming
      infection problems. The sum of frequencies of serotypes O:6, O:11, O:5 and O:16
      was more than 60%, therefore vaccination of burn patients with polyvalent
      antiserum to these serotypes could possibly produce immunity in more than half of
      the burned patients.

PMID- 12052373
TI  - Multi-resistant Acinetobacter baumannii on a burns unit--clinical risk factors
      and prognosis.
AB  - Burns patients are highly susceptible to infection, and preventing and treating
      infection are integral to the successful management of severe burns.Multi
      resistant Acinetobacter baumannii (MR-AB) strains are becoming increasingly
      important in nosocomial infections. We conducted a retrospective study of all
      adult admissions to the Singapore General Hospital (SGH) National Burns Center
      over an 18-month period. The only independent risk factors for the acquisition of
      MR-AB were the APACHE II score on admission and the number of intravascular lines
      placed. The only independent predictor of infection with MR-AB was the number of
      intravascular lines placed. The only independent predictors of longer length of
      stay were the total number of operations required and infection with MR-AB. The
      only independent predictor of mortality was the APACHE II score. This is in
      contrast to other studies that have suggested that the acquisition of MR-AB is an
      independent risk factor for mortality.

PMID- 12052374
TI  - Allogenic skin: transplant or dressing?
AB  - The use of biological dressings is an established aspect of contemporary burns
      care. The type and source of these biological materials can give rise to both
      legal and ethical issues. This paper looks at these issues in relation to
      allogenic skin. It is argued, from a medical perspective, that non-viable
      allogenic skin, cannot be transplanted and so should therefore be classified both
      medically and legally as a dressing.

PMID- 12052375
TI  - Motorcycle exhaust burns in children.
AB  - OBJECTIVES: To document and describe motorbike exhaust burns on children. DESIGN,
      PATIENTS AND SETTING: Departmental database and case note review of all children
      with motorbike exhaust burns seen at the Stuart Pegg Paediatric Burns Centre,
      Brisbane between January 1996 and October 2001. MAIN OUTCOME MEASURES: Number and
      age of children burned, circumstances of the injury, burns sustained, treatment
      required and long-term sequelae. RESULTS: Twenty-four children, median age 8
      years, sustained thermal burns, most commonly to the right lower leg. Thirteen
      children required surgery, and 17 required chronic scar management. CONCLUSIONS:
      We have identified motorbike exhausts as a cause of burns in children. The
      injuries received resulted in significant morbidity to these children and
      warrants a campaign aimed at reducing the incidence of such injuries.

PMID- 12052376
TI  - Case studies in contact burns caused by exhaust pipes of motorcycles.
AB  - Contact burns caused by the exhaust pipe of motorcycles are rarely reported. We
      performed retrospective studies of such cases in 78 patients with complete
      records. The majority of victims were unmarried (75.7%), young (<25 years,
      70.5%), and female (69.3%), dressed mostly in short pants or mini skirts (75.7%).
      The burn accident occurred mostly in late spring and early summer (52.7%), during
      rush hours (57.7%), and during parking the motorcycles (65.4%). The burn wounds
      located mostly on the lateral aspect (46.2%) of the lower leg, usually took 3-4
      weeks for complete healing. Continuous monitoring of the exhaust pipe and its
      outside cover on moving motorcycles showed that the temperature reached 170-250
      and 40-60 degrees C, respectively. For the prevention of these injuries, our
      suggestions include well-designed external shield with adequate separation from
      the exhaust pipe, motorcycle parking lots of adequate width (>120cm), the wearing
      of trousers by motorcyclists, decrease of the density of motorcycle traffic, and
      development of the electric assisted cycle in place of the fuel-driven
      motorcycle.

PMID- 12052377
TI  - Campfire burns in children: an Australian experience.
AB  - OBJECTIVES: To document and describe the effects of campfire burns on children.
      To identify the sources of danger contributing to such injuries, so that a
      prevention strategy can be devised. DESIGN, PATIENTS AND SETTING: Departmental
      database and case note review of all children with campfire burns seen at the
      Burns Unit of a tertiary referral children's hospital between January 1999 and
      June 2001. MAIN OUTCOME MEASURES: Number and ages of children burned; risk
      factors contributing to the accidents; injuries sustained; treatment required and
      long-term sequelae. RESULTS: Thirty-three children, median age 2.5 years,
      sustained burns, usually to the hands and feet, with eight requiring surgery and
      the majority requiring some form of scar therapy. Seventy-four percent of the
      children were burned by hot ashes and coals, usually from the previous night's
      fire, rather than by open flames. CONCLUSIONS: Campfires cause serious injuries
      to children. In particular, hot ashes and coals from inadequately extinguished
      campfires pose the greatest danger. Increasing the awareness of this easily
      preventable problem amongst campers is intended through a public education
      campaign.

PMID- 12052378
TI  - Distally-based neurofasciocutaneous flaps in electrical burns.
AB  - Distally-based neurocutaneous flaps have been used successfully for
      reconstruction of the lower extremity for some decades. The reconstruction of
      deep wounds exposing tendons, bones and/or vessels in electrical burns requires
      flap coverage. It is known that there is often some sub-clinical vascular damage
      in electrical burn injury. Therefore, an important part of the procedure is
      modification to improve flap viability during the reconstruction of electrical
      burn wounds. In this paper, we report our experience with the use of distally
      based sural and saphenous neurocutaneous flaps for coverage of defects in the
      lower leg and foot in 14 electrical burn patients. In 12 patients, the flaps
      survived completely, in two patients the flaps underwent partial necrosis. In
      these cases, the width of the pedicle of the neurocutaneous flap was increased
      from 3.5 to 5cm and the neurovenous pedicle was decreased to give a delay effect
      several days before the flap harvesting. We believe that these modifications
      positively effect the viability of the flap and should be used to improve
      neurocutaneous flap circulation in high risk patients.

PMID- 12052379
TI  - Enteral feeding in patients with major burn injury: the use of nasojejunal
      feeding after the failure of nasogastric feeding.
AB  - Patients with major burn injury have increased protein and energy requirements
      and early feeding is an established part of their management. The optimal method
      of feeding is unknown. Nasogastric feeding is often unsuccessful and total
      parenteral nutrition has a number of potential disadvantages. Post pyloric
      feeding is an alternative means of providing enteral nutrition. We report our
      experience of enteral feeding of patients with significant burn injury.
      Nasogastric feeding was successful in only 7 of 17 patients (41%). The commonest
      reason that nasogastric feeding failed was gastric stasis. All patients who
      failed nasogastric feeding were commenced on nasojejunal feeding and a further
      two patients were fed by this route initially. Ten of these 12 patients (83%)
      were successfully fed nasojejunally. No major adverse events attributable to
      nasojejunal feeding were identified, a nasojejunal tube was successfully placed
      in all but 1 patient and the tubes were well tolerated. We conclude that
      nasojejunal tube feeding should be considered in all patients with significant
      burn injury who cannot tolerate nasogastric tube feeding.

PMID- 12052380
TI  - Survival of a 75% burn in a patient with longstanding Addison's disease.
AB  - This is the first reported case of survival of a significant burn in a patient
      with established Addison's disease. The systemic stress response to thermal
      injury is well recognised, there is a marked hypermetabolic response with
      prolonged periods of catabolism. In particular, the elevation of plasma cortisol
      levels is crucial for this response to severe systemic stress. Cortisol elevation
      is maintained for the duration of burn wound healing, is proportional to the
      burned body surface area and the normal circadian rhythm of endogenous cortisol
      is lost. Acute adrenal insufficiency has been described in patients suffering
      major burn injuries with generally poor outcomes. We discuss the management and
      complications of adrenal replacement therapy in a severe burn setting, as
      illustrated by this case report.

PMID- 12052381
TI  - Full thickness rectus abdominis muscle defect due to a contact burn.

PMID- 12052383
TI  - Causative agents producing burn injury.

PMID- 12052382
TI  - Clostridium difficile diarrhea on a burn unit.

PMID- 12052384
TI  - A 5-year retrospective study: burn injuries due to hot cooking oil.

PMID- 12052385
TI  - The receptive fields of cat retinal ganglion cells in physiological and
      pathological states: where we are after half a century of research.
AB  - Studies on the receptive field properties of cat retinal ganglion cells over the
      past half-century are reviewed within the context of the role played by the
      receptive field in visual information processing. Emphasis is placed on the work
      conducted within the past 20 years, but a summary of key contributions from the
      1950s to 1970s is provided. We have sought to review aspects of the ganglion cell
      receptive field that have not been featured prominently in previous review
      articles. Our review of the receptive field properties of X- and Y-cells focuses
      on quantitative studies and includes consideration of the function of the
      receptive field in visual signal processing. We discuss the non-classical as well
      as the classical receptive field. Attention is also given to the receptive field
      properties of the less well-studied cat ganglion cells-the W-cells-and the effect
      of pathology on cat ganglion cell properties. Although work from our laboratories
      is highlighted, we hope that we have given a reasonably balanced view of the
      current state of the field.

PMID- 12052386
TI  - Thermotherapy in the management of choroidal melanoma.
AB  - During the past 20 years of enucleation, which was the standard treatment for
      choroidal melanoma over more than a century, has largely been replaced by eye
      salvaging therapies such as radiotherapy or local resection. In 1995
      transpupillary thermotherapy (TTT) using an infrared diode laser was introduced
      as a new conservative therapy for patients with choroidal melanoma. TTT can be
      defined as a heat treatment modality, which is delivered through a dilated pupil
      to the tumour surface. The technique uses a wide diode laser beam diameter with a
      low irradiance and a long exposure time. TTT induces tumour necrosis at sub
      photocoagulation levels by a direct cell destructive effect with only a few
      ocular complications. TTT can be performed as sole therapy or combined with
      plaque radiotherapy, thus permitting a lower radiation dose. For amelanotic
      tumours dye-enhanced TTT with indocyanine green can be used. In this paper we
      review the role of sole or combined TTT, related to the current other treatment
      modalities for choroidal melanoma.

PMID- 12052387
TI  - Vernal keratoconjunctivitis: pathogenesis and treatment.
AB  - Vernal keratoconjunctivitis (VKC) is a recurrent or chronic ocular allergic
      disease that affects mostly children and young adults living in warm climates
      worldwide. Understanding and treating VKC has been a challenge for
      ophthalmologists since the pathogenesis is unclear and anti-allergic therapy
      often unsuccessful. In this paper, the culmination of 11 years of research into
      the immunological characteristics of this disease in a group of 221 VKC patients
      will be presented. Cytological, biohumoral, immunohistological and molecular
      biological studies indicate that VKC is a Th2 lymphocyte-mediated disease. Mast
      cells, eosinophils and their mediators play major roles in the clinical
      manifestation of VKC. In addition to typical Th2-derived cytokines, IL-4, IL-5
      and IL-13, other cytokines, chemokines, growth factors and enzymes are over
      expressed in the conjunctiva of VKC patients. Furthermore, structural cells, such
      as epithelial cells and fibroblasts, are involved both in the inflammatory
      process and in the tissue remodeling phase, ultimately resulting in the formation
      of giant papillae. Interactions between specific (IgE- and Th2-mediated) and non
      specific triggers and mechanisms may account for treatment failure. New insights
      into the pathogenesis of VKC should generate the means to better design the
      strategies for this complex disease.

PMID- 12052388
TI  - LEDGF, a survival factor, activates stress-related genes.
AB  - LEDGF is a survival factor and it enhances survival of various cell types against
      stress. LEDGF is also a transcriptional activator and it binds to promoter
      elements of heat shock and stress-related genes to activate expression of these
      genes. The elevated levels of the stress-related family of proteins, such as heat
      shock proteins, antioxidant proteins, and detoxication enzymes might suppress
      apoptosis induced by stress. The protective mechanisms against stress in
      mammalian cells and in yeast are surprisingly similar.

PMID- 12052389
TI  - Proliferation of human-derived osteoblast-like cells depends on the cycle number
      and frequency of uniaxial strain.
AB  - We tested the hypothesis whether the number of applied load cycles and the
      frequency of uniaxial strain have an effect on proliferation of human bone
      derived osteoblast-like cells. A new approach was developed in order to
      differentiate between the effects of frequency and the effects of cycle number
      and strain duration. Monolayers of subconfluently grown cells were stretched in
      rectangular silicone dishes with cyclic predominantly uniaxial movement along
      there longitudinal axes. Strain was applied over 2 days varying the number of
      applied load cycles (4-3600) at a constant frequency (1Hz) or varying the
      frequency (0.1-30Hz) at a constant number of applied cycles (1800) or at a
      constant strain duration (5min). At a constant frequency, proliferative response
      increases (103%) with the number of applied cycles until a cycle number maximum
      (1800 cycles) was reached. 3600 cycles reduced cell number (43%) in contrast to
      the maximum. The variation of the frequency of applied strain tended to result in
      slight differences with regard to cell proliferation when cycle number was left
      constant. However, combined with an appropriate number of cycles there was an
      optimal frequency (1Hz) as stimulus for bone cell proliferation (84%). A higher
      frequency (30Hz) in combination with a high cycle number (9000) reduced cell
      number to control level (4%). This study demonstrates a frequency and cycle
      number dependent proliferative response of human osteoblast-like cells. It could
      be shown that effects of the frequency should not be considered separately from
      the effects of the cycle number.

PMID- 12052390
TI  - A numerical simulation of mechanical heart valve closure fluid dynamics.
AB  - A computational fluid dynamics model for the analysis of the bileaflet mechanical
      heart valve closure process is presented. The objective of the study is to
      demonstrate the ability of the numerical model to simulate the leaflet motion
      during the closing phase in order to investigate the closure fluid dynamics and
      to evaluate the effect of alterations in the leaflet tip geometry. The model has
      been applied to six different combinations of the leaflet tip geometry and the
      gap width between the leaflet tip and the housing. The results show that the
      negative pressure quickly develops on the atrial side of the leaflet tip. The
      pressure becomes more negative as the leaflet closure progresses and the lowest
      pressure is reached before the leaflet comes to a stop in the closed position.
      The flow dynamics at the instant of valve closure is strongly dependent on the
      leaflet velocity during the closing phase. Decrease of the tip velocity by a
      factor of three in the last four degrees of leaflet motion leads to a 50%
      reduction in the negative pressure magnitude.

PMID- 12052391
TI  - Estimation of cat medial gastrocnemius fascicle lengths during dynamic
      contractions.
AB  - In typical muscle models, it is often assumed that the contractile element
      (fascicle) length depends exclusively on the instantaneous muscle-tendon length
      and the instantaneous muscle force. In order to test whether the instantaneous
      fascicle length during dynamic contractions can be predicted from muscle-tendon
      length and force, fascicle lengths, muscle-tendon lengths, and muscle forces were
      directly measured in cat medial gastrocnemii during isometric and dynamic
      contractions. Two theoretical muscle models were developed: model A was based on
      force-time data obtained during the activation phase and model D on force-time
      data obtained during the deactivation phase of isometric contractions. To test
      the models, instantaneous fascicle lengths were predicted from muscle-tendon
      lengths and forces during dynamic contractions that simulated cat locomotion for
      speeds ranging from 0.4 to 1.6m/s. The theoretically predicted fascicle lengths
      were compared with the experimentally measured fascicle lengths. It was found
      that fascicle lengths were not uniquely associated with muscle-tendon lengths and
      forces; that is, for a given muscle-tendon length and force, fascicle lengths
      varied depending on the contractile history. Consequently, models A and D
      differed in fascicle length predictions; model D (maximum average error=8.5%) was
      considerably better than model A (maximum average error=22.3%). We conclude from
      this study that it is not possible to predict the exact fascicle lengths from
      muscle-tendon lengths and forces alone, however, adequate predictions seem
      possible based on such a model. The relationship between fascicle length and
      muscle force and muscle-tendon length is complex and highly non-linear, thus, it
      appears unlikely that accurate fascicle length predictions can be made without
      some reference contractions in which fascicle length, muscle-tendon length, and
      force are measured simultaneously.

PMID- 12052392
TI  - Comparison of the equilibrium response of articular cartilage in unconfined
      compression, confined compression and indentation.
AB  - At mechanical equilibrium, articular cartilage is usually characterized as an
      isotropic elastic material with no interstitial fluid flow. In this study, the
      equilibrium properties (Young's modulus, aggregate modulus and Poisson's ratio)
      of bovine humeral, patellar and femoral cartilage specimens (n=26) were
      investigated using unconfined compression, confined compression, and indentation
      tests. Optical measurements of the Poisson's ratio of cartilage were also carried
      out. Mean values of the Young's modulus (assessed from the unconfined compression
      test) were 0.80+/-0.33, 0.57+/-0.17 and 0.31+/-0.18MPa and of the Poisson's ratio
      (assessed from the optical test) 0.15+/-0.06, 0.16+/-0.05 and 0.21+/-0.05 for
      humeral, patellar, and femoral cartilages, respectively. The indentation tests
      showed 30-79% (p<0.01) higher Young's modulus values than the unconfined
      compression tests. In indentation, values of the Young's modulus were independent
      of the indenter diameter only in the humeral cartilage. The mean values of the
      Poisson's ratio, obtained indirectly using the mathematical relation between the
      Young's modulus and the aggregate modulus in isotropic material, were 0.16+/
      0.06, 0.21+/-0.05, and 0.26+/-0.08 for humeral, patellar, and femoral cartilages,
      respectively. We conclude that the values of the elastic parameters of the
      cartilage are dependent on the measurement technique in use. Based on the similar
      values of Poisson's ratios, as determined directly or indirectly, the equilibrium
      response of articular cartilage under unconfined and confined compression is
      satisfactorily described by the isotropic elastic model. However, values of the
      isotropic Young's modulus obtained from the in situ indentation tests are higher
      than those obtained from the in vitro unconfined or confined compression tests
      and may depend on the indenter size in use.

PMID- 12052393
TI  - The effect of physical exercise on the dynamics of glucose and insulin.
AB  - Regular physical activity is indicated either to prevent and delay the onset of
      non-insulin-dependent diabetes or to assure a good control of diabetes by
      increasing insulin sensitivity and ameliorating the metabolism of glucose
      disappearance. Many studies and experiments have dealt with this subject. In this
      paper, we introduce the effect of physical activity via parameters of a
      mathematical model which allows us to compare the behaviour of blood glucose in
      normal, non-insulin-dependent diabetes and insulin-dependent diabetes people,
      with and without physical effort. Extreme cases of physical activity leading to
      hypoglycaemia or aggravating hyperglycaemia are also underlined.

PMID- 12052394
TI  - Modeling the length dependence of isometric force in human quadriceps muscles.
AB  - Functional electrical stimulation is used to restore movement and function of
      paralyzed muscles by activating skeletal muscle artificially. An accurate and
      predictive mathematical model can facilitate the design of stimulation patterns
      that produce the desired force. The present study is a first step in developing a
      mathematical model for non-isometric muscle contractions. The goals of this study
      were to: (1) identify how our isometric force model's parameters vary with
      changes in knee joint angle, (2) identify the best knee flexion angle to
      parameterize this model, and (3) validate the model by comparing experimental
      data to predictions in response to a wide range of stimulation frequencies and
      muscle lengths. Results showed that by parabolically varying one of the free
      parameters with knee joint angle and fixing the other parameters at the values
      identified at 40 degrees of knee flexion, the model could predict the force
      responses to a wide range of stimulation frequencies and patterns at different
      muscle lengths. This work showed that the current isometric force model is
      capable of predicting the changes in skeletal muscle force at different muscle
      lengths.

PMID- 12052395
TI  - Elastic anisotropy of articular cartilage is associated with the microstructures
      of collagen fibers and chondrocytes.
AB  - Chondrocyte shape and volumetric concentration change as a function of depth in
      articular cartilage. A given chondrocyte shape produces different effects on the
      global material properties depending on the structure of the collagen fiber
      network. The shape and volumetric concentration of chondrocytes in articular
      cartilage appear to be related to the mechanical stability of the matrix. The
      present study was aimed to investigate, theoretically, the effects of the
      structural arrangement of the collagen fiber network, and the shape and
      distribution of chondrocytes, on the global material behavior of articular
      cartilage. Articular cartilage was assumed to be a four-phasic composite
      comprised of a matrix (associated with the properties of the proteoglycan
      structure), vertically and horizontally distributed collagen fibers, and
      spheroidal inclusions representing chondrocytes. A solution for composite
      materials was used to estimate the global, effective material properties of
      cartilage. Only the elasticity of the solid phase was investigated in the present
      study. Our simulations suggest that a soft, spheroidal cell inclusion in a fiber
      reinforced proteoglycan matrix affects the material properties differently
      depending on the shape of the spheroidal inclusions. If the long axis of the
      inclusions is parallel to the collagen fibers, as in the deep zone, the soft
      inclusions increase the stiffness of the composite in the fiber direction, and
      reduce the stiffness of the composite in the direction normal to the fibers.
      Furthermore, we found that Young's modulus normal to the contact surface
      increases from the superficial to the deep zone in articular cartilage by a
      factor of 10-50, a finding that agrees well with experimental observations. Our
      analysis suggests that the combination of proteoglycan matrix, fiber orientation,
      and shape of chondrocytes are intimately related and are likely adapted to
      optimize the mechanical stability and load carrying capacity of the structure.

PMID- 12052396
TI  - Ligament material behavior is nonlinear, viscoelastic and rate-independent under
      shear loading.
AB  - The material behavior of ligament is determined by its constituents, their
      organization and their interaction with each other. To elucidate the origins of
      the multiaxial material behavior of ligaments, we investigated ligament response
      to shear loading under both quasi-static and rate-dependent loading conditions.
      Stress relaxation tests demonstrated that the tissue was highly viscoelastic in
      shear, with peak loads dropping over 40% during 30 min of stress relaxation. The
      stress relaxation response was unaffected by three decades of change in shear
      strain rate (1.3, 13 and 130%/s). A novel parameter estimation technique was
      developed to determine material coefficients that best described the experimental
      response of each test specimen to shear. The experimentally measured clamp
      displacements and reaction forces from the simple shear tests were used with a
      nonlinear optimization strategy based around function evaluations from a finite
      element program. A transversely isotropic material with an exponential matrix
      strain energy provided an excellent fit to experimental load-displacement curves.
      The shear modulus of human MCL showed a significant increase with increasing
      shear strain (p<0.001), reaching a maximum of 1.72+/-0.4871 MPa. The results
      obtained from this study suggest that viscoelasticity in shear does not likely
      result from fluid flow. Gradual loading of transversely oriented microstructural
      features such as intermolecular collagen crosslinks or collagen-proteoglycan
      crosslinking may be responsible for the stiffening response under shear loading.

PMID- 12052398
TI  - An alternative ultrasonic method for measuring the elastic properties of cortical
      bone.
AB  - We studied the elastic properties of bone to analyze its mechanical behavior. The
      basic principles of ultrasonic methods are now well established for varying
      isotropic media, particularly in the field of biomedical engineering. However,
      little progress has been made in its application to anisotropic materials. This
      is largely due to the complex nature of wave propagation in these media. In the
      present study, the theory of elastic waves is essential because it relates the
      elastic moduli of a material to the velocity of propagation of these waves along
      arbitrary directions in a solid. Transducers are generally placed in contact with
      the samples which are often cubes with parallel faces that are difficult to
      prepare. The ultrasonic method used here is original, a rough preparation of the
      bone is sufficient and the sample is rotated. Moreover, to analyze heterogeneity
      of the structure we measure velocities in different points on the sample. The aim
      of the present study was to determine in vitro the anisotropic elastic properties
      of cortical bones. For this purpose, our method allowed measurement of
      longitudinal and transverse velocities (C(L) and C(T)) in longitudinal (fiber
      direction) and the radial directions (orthogonal to the fiber direction) of
      compact bones. Young's modulus E and Poisson's ratio nu, were then deduced from
      the velocities measured considering the compact bone as transversely isotropic or
      orthotropic. The results are in line with those of other methods.

PMID- 12052397
TI  - A study of the effect of non-linearities in the equation of bone remodeling.
AB  - In this paper, we introduced a high-order non-linear equation of bone remodeling
      to combine with FEM by introducing two non-linearities, i.e. the remodeling
      coefficient B(t) and the order of non-linear remodeling equation. The influence
      of each non-linearity was tested based on its mechanical and physiological
      implications discussed. We use two finite element models to investigate the
      influences of non-linearities in this equation: a plate subjected to a ramp load,
      and a 2D model of the cross-section of a vertebra. By importing the idea of
      topology optimization in engineering, their external shapes and internal density
      distributions were simulated from unfixed configurations. To a certain extent,
      the high-order non-linear equation of bone remodeling we suggested here can
      control the remodeling processes of bones in different stages of growth or at
      different anatomic sites more effectively, and make it more consistent with
      physiological reality, i.e. express the remodeling characteristic that bone's
      best morphology is adapted to its mechanical environment. Furthermore, it is
      likely to describe the process of bone growth and evolution.

PMID- 12052399
TI  - The effects of tibial component inclination on bone stress after unicompartmental
      knee arthroplasty.
AB  - Unlike the case with total knee arthroplasty, the femorotibial angle (FTA) after
      unicompartmental knee arthroplasty (UKA) does not directly depend on the
      inclination of the tibial component when the height of the joint line is
      maintained. This study analyzed the effects of the inclination of the tibial
      component in the coronal plane on the contact pressure of the implant-bone
      surface and the stresses on the proximal tibia. A two-dimensional, coronal plane
      model of the proximal tibia was subjected to finite-element analysis. Sixteen
      patterns of finite-element models of equal FTA were developed in which the
      inclination of tibial components ranged from 5 degrees valgus to 10 degrees varus
      in increments of 1 degrees. Stress concentration at the proximal medial
      diaphyseal cortex gradually increased as the inclination changed from valgus to
      varus. Maximum contact pressure on the metal-bone interface similarly changed and
      shifted from the lateral edge to the medial edge of the implant as the
      inclination changed to varus. It was found that even without changing FTA, the
      inclination of the tibial component might affect stress concentration and contact
      pressure in the proximal tibia after UKA. The results suggested that slight
      valgus inclination of the tibial component might be preferable to varus and even
      to 0 degrees (square) inclination so far as the stress distribution is concerned.

PMID- 12052401
TI  - Precision of estimates of mean and peak spinal loads in lifting.
AB  - A bootstrap procedure was used to determine the statistical precision of
      estimates of mean and peak spinal loads during lifting as function of the numbers
      of subjects and measurements per subject included in a biomechanical study. Data
      were derived from an experiment in which 10 subjects performed 360 lifting trials
      each. The maximum values per lift of the lumbar flexion angle, L5S1 sagittal
      plane moment, and L5S1 compression force were determined. From the data set thus
      compiled, 3000 samples were randomly drawn for each combination of number of
      subjects and number of measurements considered. The coefficients of variation of
      mean and peak (defined as mean plus 2 standard deviations) spinal loads across
      these samples were calculated. The coefficients of variation of the means of the
      three parameters of spinal load decreased as a linear function of the number of
      subjects to a power of about -0.48 and number of measurements to a power of about
      -0.06, while the corresponding powers for peak loads were about -0.44 and -0.11.

PMID- 12052400
TI  - Mass properties of the human mandible.
AB  - Computer simulation of human masticatory dynamics requires specification of the
      jaw's mass properties. These are difficult to estimate, especially in living
      subjects. Here, we used calibrated computed tomography (CT) to determine the
      properties of eight osseous jaw specimens with adult dentitions. When the CT
      numbers were converted to mineral densities, the mean estimated jaw mass was 13%
      greater than the mean wet weight. Putative bone marrow accounted for an extra 7%
      of mass. The mean bone densities for the sample were very consistent (1.72+/
      0.02g/cm(3)). The mass and geometric centers were close (mean linear difference
      0.43+/-0.18mm), and were always located anteroposteriorly between the second and
      third molars. The largest moment of inertia (MI) occurred around the jaw's
      superoinferior axis, and the smallest around its transverse axis. Bone marrow
      added an extra 7% to the MIs. There were linear relationships between the
      mandibular length (expressed three dimensionally), the actual and estimated
      masses, and the moments of inertia. Our study suggests non-invasive imaging (such
      as magnetic resonance) and even direct linear measurement, may be adequate to
      estimate jaw mass properties in living humans.

PMID- 12052402
TI  - A precise radiographic technique for the measurement of dimensional changes in
      heart valve biomaterials following fixation.
AB  - Accurate tissue thickness measurements are difficult to acquire by present
      techniques. Error is introduced by tissue compression during measurements or by
      tissue processing prior to measurement. In the field of valve replacement, tissue
      dimensional changes from fixation prior to implantation may predispose implants
      to premature tissue failure and it becomes important to have an accurate method
      for comparing cusp dimensions pre- and post-fixation. A new approach is to use
      high-resolution digital radiography to make thickness maps of entire specimens.
      For 25 matched porcine aortic valve cusps, we have evaluated this technique's
      ability to measure and compare thickness, surface area and volume before and
      after 7 days of aldehyde fixation. Digital radiographs were acquired pre- and
      post-0.5% glutaraldehyde (n=13) or 10% formaldehyde (n=12) fixation. Mean
      thickness, surface area, volume and four measurements to evaluate shape
      differences with fixation were obtained and compared pre- and post-fixation using
      paired t tests. The results demonstrate that this X-ray imaging technique can
      provide dimensions of matched fresh and fixed specimens and is sensitive enough
      to show statistically significant changes due to fixation. These findings also
      illustrate that aldehyde fixation can cause tissue contraction resulting in a
      significant overall increase in tissue thickness and a decrease in surface area.
      This technique could be used to gain further insights into tissue anatomy and
      mechanics.

PMID- 12052403
TI  - A mathematical formula to calculate the theoretical range of motion for total hip
      replacement.
AB  - The reduced range of motion (ROM) resulting from total hip replacement (THR)
      leads to frequent prosthetic impingement, which may restrict activities of daily
      living and cause subluxation and dislocation. Therefore, to know the ROM of THR
      is very important in clinical situations and in the design of prostheses. THR
      involves a pure ball and socket joint. We created a mathematical formula to
      calculate the theoretical ROM of THR limited by the prosthetic impingement. The
      ROM of THR is governed by the following five factors, (1) The prosthetic ROM
      (oscillation angle: obtained from company data), (2) cup abduction (3) cup
      anterior opening, (4) the angle of the femoral neck component from the horizontal
      plane, and (5) the femoral neck anteversion. The last 4 factors are able to be
      obtained from anterior-posterior, axial X-rays and CT of the patient's THR. The
      objective was to create mathematical formulas that could accurately and quickly
      calculate the ROM of THR. By entering the five values into a computer programmed
      with the formulas, one could obtain the ROM for the THR. This reveals the effect
      on ROM of the oscillation angle and the interaction of ROM with cup abduction,
      anterior opening and neck anteversion. Furthermore this readily would enable a
      clinical evaluation of the possibility of postoperative dislocation and help in
      postoperative rehabilitation. The calculated numerical values of ROM by these
      mathematical formulas were successfully compared with the ROMs obtained from 3
      dimensional computer graphics (3D-CG).

PMID- 12052404
TI  - Nanoindentation and storage of teeth.
AB  - This study determined changes in nanomechanical properties of dentin and enamel
      during storage in deionized water, calcium chloride buffered saline solution and
      Hank's balanced salts solution (HBSS). Atomic force microscopy based
      nanoindentation showed that storing teeth in deionized water or CaCl(2)-solution
      resulted in a large decrease in elastic modulus and hardness. At 1 day a decrease
      in the mechanical properties values of up to 20% and 30% was observed for enamel
      and dentin, respectively. After 1 week, mechanical properties dropped below 50%
      of their starting values, which is attributed to a demineralization process
      during storage. In contrast, storing teeth in HBSS did not significantly alter
      the mechanical properties for a time interval of 2 weeks. The use of HBSS for
      storage of samples from teeth is recommended.

PMID- 12052405
TI  - Reproducible volar partial lacerations in flexor tendons: a new device for
      biomechanical studies.
AB  - A device was designed to create clinically relevant, precise partial flexor
      digitorum profundus tendon lacerations for in vitro studies but can be adapted
      for in vivo studies. This caliper-based system utilizes a direct measurement of
      the tendon height and assumes an elliptical cross section to select the depth of
      the cut. The accuracy was tested on 60 cuts on 12 human tendons lacerated to an
      expected 50% or 75% of their cross-sectional area, based on the assumption that
      the cross-section was elliptical in shape. The cuts were made in portions of the
      tendon that varied in cross-sectional shape and size. The cut surface of the
      laceration was colored with Methylene blue and then the laceration was completed.
      The tendon cross-section was digitally imaged and the respective areas of the
      stained and unstained regions were evaluated using image-processing software. The
      mean lacerated areas were 52% (SD 5%) and 73% (SD 6%) for targeted lacerations of
      50% and 75%, respectively. The device thus appears to be accurate within an
      acceptable 5% margin of error from the expected area, and adaptable to intra- and
      inter-tendinous size variations.

PMID- 12052406
TI  - The use of Roentgenstereofluorogrammetry to predict the 3-D spatial coordinates
      of points in low speed events.
AB  - Imaging technologies such as cine-radiography, cine-MRI, and X-ray stereo
      photogrammetry have become popular diagnostic tools in biomechanical studies of
      musculoskeletal systems. However, their widespread use for research purposes has
      been restricted due to their high cost and somewhat limited availability. In an
      attempt to develop a reliable low cost system, a dual-fluoroscopic system capable
      of tracking the 3-D spatial motion of discrete landmark points in real time was
      developed. A simple methodology was developed to convert the analog fluoroscopic
      images to digital files for post-processing. A custom computer code based on the
      principles of X-ray stereo photogrammetry was also developed to predict 3-D
      coordinates from the 2-D images from the individual flouroscopes. The goal of the
      current study was to assess the accuracy and resolution of this system by using
      it to predict the motion of a test point following a known curvilinear
      trajectory. Our system predicted the time-varying motion and path of the test
      point within 0.25%. However, the current system is limited to studying low speed
      events only (max event frequency of 3Hz) due to the limited sampling frequency of
      the A/D conversion employed here.

PMID- 12052407
TI  - Digital video combined with conventional radiography creates an excellent high
      speed X-ray video system.
AB  - Analysing rapid internal movement in animals requires high-speed X-ray imaging to
      visualise motion of bony and soft body structures. The frame rate of X-ray
      cinematic camera is limited to 200 frames s(-1) with a shutter speed of 1/3000s,
      due to the low X-ray kV, required for small animals. These rates are often too
      slow for analysing the rapid accelerations of which small animals are capable.
      Here, we present three alternative digital-video systems that can be combined
      with a conventional X-ray intensifier to yield excellent slow-motion images of
      internal body parts of small animals. Each system shows high performance for
      different requirements of radiographic motion analysis.

PMID- 12052408
TI  - Eales disease--an update.
AB  - Eales disease, first described by Henry Eales in 1880, remains an enigma. The
      disease, observed more commonly in the Indian subcontinent than in the rest of
      the world, occurs in young healthy adult males, initially presenting as retinal
      periphlebitis and later as retinal ischemia that may lead to vascular alterations
      and neovascularization. Recurrent vitreous hemorrhage with or without retinal
      detachment is the common sequelae. In recent years, immunological, molecular
      biological, and biochemical studies have indicated the role of human leukocyte
      antigen, retinal autoimmunity, mycobacterium tuberculosis genome, and free
      radical mediated damage in the etiopathogenesis of this disease. However, its
      etiology appears to be multifactorial. The management depends on the stage of the
      disease and consists of medical treatment with oral corticosteroids in the active
      inflammatory stage and laser photocoagulation in the advanced retinal ischemia
      and neovascularization stages. The results of vitreoretinal surgery have been
      found to be satisfactory in case of vitreous hemorrhage with or without retinal
      detachment.

PMID- 12052409
TI  - Primary anti-phospholipid antibody syndrome (APS): current concepts.
AB  - Primary anti-phospholipid syndrome (APS) is a thrombophilic state characterized
      by recurrent arterial and venous thrombosis, recurrent pregnancy loss, and the
      presence of circulating anti-phospholipid antibodies that may be responsible for
      thrombophilia and pregnancy morbidity. Ophthalmologic features are present in 15
      88% of the patients with primary APS, thus ophthalmologists are one of the first
      physicians to whom the patient will present. An accurate diagnosis may save the
      patient from recurrent, potentially life-threatening thrombosis. In the U.S.A.,
      an estimated 35,000 new cases of APS-related venous thrombosis occur each year in
      a population that is several decades younger than the patient population
      typically affected by thrombosis. Clinical features, such as chorea, transverse
      myelitis, cardiac valvular lesions, and accelerated atherosclerosis, are
      hypothesized to be due to a direct tissue-antibody interaction and cannot be
      explained purely by thrombosis. The use of recently proposed, well-defined
      diagnostic criteria, and better standardization of laboratory assays for the anti
      phospholipid antibodies should help enable epidemiological surveys to establish
      the prevalence of these antibodies in patients with thrombosis and in the general
      population. Diagnosis of APS should be considered in all patients with recurrent
      systemic or ocular thrombosis in the absence of known risk factors. Several well
      designed prospective studies show an increased risk of thrombosis in the presence
      of medium to high antibody level. With ocular involvement in as many as 88% of
      APS patients, an ophthalmic assessment should be an integral part of the clinical
      work-up of any patient with suspected or confirmed APS. The presence of isolated
      ocular thrombophilia with persistently elevated anti-phospholipid antibodies or
      lupus coagulant should confirm the diagnosis of APS. Management of these patients
      must be a multi-disciplinary effort with either a rheumatologist or a
      hematologist having the overall responsibility for coordinating treatment and
      monitoring the patient's immune status and anticoagulation. Treatment of isolated
      ocular thrombophilia in the presence of moderate to high titers of
      antiphospholipid antibodies should be on the same principles as patients with APS
      to prevent recurrent ocular or cerebral thrombosis.

PMID- 12052410
TI  - Matrix metalloproteinases in disease and repair processes in the anterior
      segment.
AB  - The pathogenesis of many anterior segment disorders and ocular complications
      following surgery are secondary to the wound healing response. The extent of
      clinical damage observed is closely related to the amount of scarring and tissue
      contraction. Matrix metalloproteinases (MMPs) are a family of enzymes that play a
      vital role in all stages of the wound healing process. They degrade all
      extracellular matrix components and also have the ability to synthesize collagen
      and extracellular matrix members, and are therefore important in the remodeling
      of a wound. Overexpression of MMPs results in excessive extracellular matrix
      degradation, leading to tissue destruction and loss of organ function. In the
      case of the anterior segment, this may mean the loss of visual function. This
      review focuses on the role MMPs have in the development of various anterior
      segment disorders. The importance of MMPs in the wound healing response and its
      potential modulation to manipulate the scarring response is being recognized, and
      current developments will be described.

PMID- 12052411
TI  - Bilateral decreased vision and cotton-wool spots in a 42-year-old man.
AB  - A 42-year-old man presented with bilateral decreased vision, transient visual
      loss, and anterior segment inflammation. The diagnosis of ocular ischemic
      syndrome was established by arteriography.

PMID- 12052412
TI  - Ahhh, that's a strange eye movement.
AB  - A 57-year-old woman presents with sudden onset of horizontal diplopia following
      surgical repair of a ruptured posterior fossa aneurysm. Neuro-ophthalmic
      examination revealed a left gaze palsy, right abducens palsy, bilateral facial
      nerve palsy, reverse ocular bobbing and oculopalatal myoclonus. These findings
      can be localized to the anterior pons caused by damage to the midline perforator
      vessels resulting in anterior pontine pathology. A video demonstration of the
      oculopalatal myoclonus and other types of vertical nystagmus is provided. The
      etiology and characteristics of these forms of nystagmus is discussed.

PMID- 12052413
TI  - Eye disease and care in Latin America and the Caribbean.
AB  - In the last decade, health indicators in Latin America and the Caribbean reflect
      advances. The per capita public expenditure on health care has increased in many
      countries. Despite these improvements, it is estimated that for every million
      population in Latin America and the Caribbean, 5,000 are blind and 20,000 are
      visually impaired; at least 66% of the blindness is attributable to treatable
      conditions such as cataract. The cataract surgery rate in the region remains low
      as compared to the industrialized countries, although it is higher than many
      other regions of the world. The availability of eye care services varies from
      country to country within the region, and the number of ophthalmologists per
      million population in the richest countries may be nine times more than in the
      poorest. Access, defined as the distance between the consumer and the services,
      is problematic in countries with isolated areas in the rainforest or high
      mountains, poor road systems, or lack of public transportation. Affordability is
      an important issue that limits utilization of services by the poorest segments of
      the population in nearly all countries in Latin America and the Caribbean.

PMID- 12052414
TI  - The ophthalmic trials of G. H. A. Hansen.
AB  - G. H. A. Hansen (1841-1912) is widely known as the discoverer of the infectious
      cause of leprosy. It is less well known that his career was threatened by an
      episode involving experimentation on the eye. As a staff physician at the leprosy
      hospitals of Bergen, Norway, early in his career, Hansen learned about ocular
      involvement in leprosy and co-authored Leprous Diseases and the Eye. In 1873 he
      observed bacilli in leprous nodules, but proof of an infectious origin was
      difficult to obtain because the agent could not be cultured and no one had
      demonstrated direct transmission. Hansen tried several unsuccessful experiments,
      and in 1879 he passed a cataract knife that had incised an active leprous nodule
      into a woman's conjunctiva. No nodule developed, but the woman complained of pain
      and said she was never asked for permission. Hansen was brought to trial where
      eminent physicians testified on his behalf-but Hansen himself readily admitted
      that no permission had been sought for fear the woman would say no. He was
      convicted, and relieved of his post as staff physician, but he was allowed to
      retain an appointment as Chief Medical Officer of Health for Leprosy, in which
      capacity he worked for the rest of his life.

PMID- 12052419
TI  - Ophthalmic manifestations of lightning [correction of lightening] strikes.

PMID- 12052423
TI  - Quality assured trusted third parties for deploying secure internet-based
      healthcare applications.
AB  - In this paper we present a complete reference framework for the provision of
      quality assured Trusted Third Party (TTP) services within a medical environment.
      The main objective is to provide all the basic guidelines towards the development
      of a quality system for a TTP as an organisation, which could be mapped directly
      to the requirements of ISO-9000 standards. The important results of the
      implementation of a quality system, are the enhanced trustworthiness of the TTP
      and the confidence of the medical society in the provided services. Furthermore,
      the value added certification services conform to customer requirements and are
      characterised by efficiency, reliability, security, credibility and trust. The
      internal organisation acquires a clear and strict structure and maximises its
      effectiveness by establishing quality management, committed to control, assure
      and improve quality. The TTP requirements for quality are identified and the
      various elements of the quality system are described illustratively.

PMID- 12052421
TI  - The tubulointerstitial nephritis and uveitis syndrome.

PMID- 12052424
TI  - The computerized patient record: balancing effort and benefit.
AB  - PROMISE AND REALITY: this review addresses two questions. First, why is the
      introduction of the computerized patient record (CPR) so slow, while its
      potential for improved quality of care and reduction of cost is well recognized?
      Second, what, in this respect, is the role of record architecture and
      standardization? BARRIERS: the impediments for CPR adoption are put in a larger
      context by addressing the relationship among effort, benefit, and the parties
      involved. An important financial impediment is insufficient return of investment.
      Other hurdles related to the use of CPRs are lack of integration and flexibility,
      which cause clinicians to experience insufficient reward to motivate them for
      data entry and changes in working style. Effort and benefit have to be balanced
      for each party involved. REQUIREMENTS FOR IMPROVEMENT: lack of standardization
      impedes exchange and sharing of medical data, and new developments cause fear of
      applications to become outdated. Flexibility in content and use, integration, and
      adaptability to change, are key requirements for CPR systems. These requirements
      can most effectively be met through an architecture that separates content and
      structure, such that the road to standardization is not paved with frequent
      expensive adaptations. STRATEGIES FOR IMPLEMENTATION: successful implementation
      and acceptance require reliable evaluation of applications by independent
      professional groups. Users need to be involved in setting priorities and planning
      for actual implementation.

PMID- 12052425
TI  - Minimum data set development: air transport time-related terms.
AB  - The purpose of this research was to identify, name and define a set of concepts
      to describe specific times and time intervals relevant to patient transport by
      helicopter. A list of 206 potential terms was identified from 96 patient records.
      A purposive sample of experts representing nurses, physicians, paramedics, pilots
      and communication specialists involved in air transport was selected to
      participate in a five-round Delphi study conducted by email. A set of 19 concepts
      were identified and defined. Fifteen of the terms were specific times, such as
      Time of Call, Depart Base and Arrive Location. Four of the terms were intervals,
      such as Ground Time or Transport Time.

PMID- 12052426
TI  - Computerisation, coding, data retrieval and related attitudes among Swedish
      general practitioners-a survey of necessary conditions for a database of diseases
      and health problems.
AB  - OBJECTIVE: To investigate necessary conditions for the establishment of a
      database of diseases and health problems for research and health care planning,
      based on electronic patient records in everyday clinical use among general
      practitioners (GPs). DESIGN: Postal questionnaire study. SETTING: Primary health
      care in Sweden. SUBJECTS: Three hundred randomly selected GPs. MAIN OUTCOME
      MEASURES: Degree of computerisation of patient records. User frequency and
      characteristics of diagnosis classification systems and coding tools. Frequency
      of coding activities and retrieval of codes, and related attitudes. Opinions on a
      primary health care version of ICD-10. RESULTS: A total of 184 GPs (61% of the
      300 GPs) were included in the study. About 92% used an electronic record system,
      some type of diagnostic classification was used by 93%, and ICD based
      classifications by 88%. The classification in use was computerised for 74%.
      Mainly simple tools were used to retrieve diagnostic codes. About 76% of GPs
      reported classifying at least one symptom or disease per encounter. The codes
      were retrieved 'once a month' or more by 19%. Classification of diseases was
      considered important for follow-up by 83%, and for the care of the patient by 75%
      of the GPs. The primary health care version of ICD-10 with a total of 972 codes
      was considered too limited in size by 31%. CONCLUSION: Electronic patient records
      in everyday clinical use in Swedish general practice provide several fundamentals
      for a database of diagnostic data. However, there are several barriers to the
      establishment of such a database that is both valid and reliable.

PMID- 12052427
TI  - Automatic calculation of a modified APACHE II score using a patient data
      management system (PDMS).
AB  - OBJECTIVE: To investigate a fully automated and modified APACHE II score
      calculation exclusively based on routine data supplied by patient data management
      system, the ICUData, and to assess the predictive performance of this score using
      analysis of discrimination and calibration at an operative ICU. METHOD: SQL
      scripts (calculation programs) were developed to calculate the scores of 524
      patients who stayed at the ICU between April 1st, 1999 and March 31st, 2000. The
      calculation programs considered unavailable data as 'not pathological'. The main
      outcome measure was survival status at ICU discharge. The discriminative power on
      mortality of this modified APACHE II score was checked with a receiver operating
      characteristic (ROC) curve. Calibration was tested using the Hosmer-Lemeshow
      goodness-of-fit test. RESULTS: The 459 survivors had an average APACHE score of
      17.8+/-5.3. The score of the 65 deceased patients averaged 22.7+/-4.6. The area
      under the ROC curve of 0.790 was significantly >0.5 (P<0.01) and had a 95%
      confidence interval (CI) of 0.712-0.825. The goodness-of-fit test showed a good
      calibration (H=4.89, P=0.70, dof 7, C=6.96, P=0.541, dof 8). CONCLUSION: A
      prediction model based on completely automatically calculated 'modified APACHE II
      scores' can be constructed using data collected with PDMS. However, due to
      differences in the patient collective and methods used, the results need
      validation and can only be partially compared to results from other studies.

PMID- 12052428
TI  - Wiring a medical school and teaching hospital for telemedicine.
AB  - The planning and installation of a telemedicine system for communication within a
      teaching hospital and its academic and hospital units with a capacity for
      accommodation of up to 400 video-stations is described. The system is intended
      for improving the communication between patients and health professionals, and
      between the health professionals themselves. It also provides the basis for
      improving pre-graduate teaching, especially problem-based learning, and all
      aspects of postgraduate teaching.

PMID- 12052429
TI  - Modulation of heterocyclic amine-induced mutagenicity and carcinogenicity: an 'A
      to-Z' guide to chemopreventive agents, promoters, and transgenic models.
AB  - A landmark report by Widmark in 1939 describing "cancer-producing substances in
      roasted food", and the seminal work of Sugimura and colleagues in the 1970s on
      the isolation of potent mutagens from cooked meat and fish stimulated a major
      international effort on the study of heterocyclic amines and their modulators.
      The latter term is used in its broadest context to mean agents or conditions that
      positively or negatively influence the mutagenic or carcinogenic activities of
      heterocyclic amines in vitro or in vivo. An 'A-to-Z' list of these modulators
      includes well over 150 natural or synthetic phytochemicals, micronutrients and
      antioxidants, as well as several large chemical classes (polyphenols, flavones,
      retinoids, porphyrins), food fractions, and food preparation methods. In many
      cases, the findings reported in the literature can be regarded as descriptive,
      but for a number of specific agents there is sufficient evidence to glean some
      understanding of the inhibitory or promotional mechanisms of action. These
      mechanisms can be divided into 11 separate sub-categories, arranged within a
      general classification scheme that encompasses such terms as 'blocking agents',
      'suppressing agents', 'desmutagens', 'bioantimutagens', 'interceptor molecules'
      and 'tumor promoters'. In addition, new research directions, most notably during
      the past 2-3 years or so, have led to the use of novel dosing protocols and
      unique animal models (including transgenic species) that provide insight into
      exposure conditions and genetic background as modulators of heterocyclic amine
      activity in vitro and in vivo. Overall, the more than 250 citations on the
      subject give ample evidence of the growing interest in modulators of heterocyclic
      amine carcinogenesis and mutagenesis, and their possible importance in
      determining human cancer risk in defined populations.

PMID- 12052430
TI  - Mutations and their use in insect control.
AB  - Traditional chemically based methods for insect control have been shown to have
      serious limitations, and many alternative approaches have been developed and
      evaluated, including those based on the use of different types of mutation. The
      mutagenic action of ionizing radiation was well known in the field of genetics
      long before it was realized by entomologists that it might be used to induce
      dominant lethal mutations in insects, which, when released, could sterilize wild
      female insects. The use of radiation to induce dominant lethal mutations in the
      sterile insect technique (SIT) is now a major component of many large and
      successful programs for pest suppression and eradication. Adult insects, and
      their different developmental stages, differ in their sensitivity to the
      induction of dominant lethal mutations, and care has to be taken to identify the
      appropriate dose of radiation that produces the required level of sterility
      without impairing the overall fitness of the released insect. Sterility can also
      be introduced into populations through genetic mechanisms, including
      translocations, hybrid incompatibility, and inherited sterility in Lepidoptera.
      The latter phenomenon is due to the fact that this group of insects has
      holokinetic chromosomes. Specific types of mutations can also be used to make
      improvements to the SIT, especially for the development of strains for the
      production of only male insects for sterilization and release. These strains
      utilize male translocations and a variety of selectable mutations, either
      conditional or visible, so that at some stage of development, the males can be
      separated from the females. In one major insect pest, Ceratitis capitata, these
      strains are used routinely in large operational programs. This review summarizes
      these developments, including the possible future use of transgenic technology in
      pest control.

PMID- 12052431
TI  - Is metronidazole carcinogenic?
AB  - Metronidazole (MTZ, 1-[2-hydroxyethyl]-2-methyl-5-nitroimidazole), an
      antiparasitic and antibacterial compound, is one of the world's most used drugs.
      MTZ is potentially carcinogenic to humans due to the following facts: it is a
      proven mutagen in bacterial systems, it is genotoxic to human cells and also, it
      is carcinogenic to animals. However, due to inadequate epidemiological evidence,
      it is not considered as a risk factor for cancer in humans. As it will be
      discussed here, the existing population studies are deficient since they have not
      included sufficient sample size, the follow-up time has not been long enough, and
      the individual sensitivity to the drug might have been acting as a confounding
      factor. Due to the increasing use of this drug, more and improved studies are
      needed to elucidate its mechanism of genotoxicity and its carcinogenic potential.

PMID- 12052432
TI  - DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways:
      fail-safe protection against carcinogenesis.
AB  - Two systems are essential in humans for genome integrity, DNA repair and
      apoptosis. Cells that are defective in DNA repair tend to accumulate excess DNA
      damage. Cells defective in apoptosis tend to survive with excess DNA damage and
      thus allow DNA replication past DNA damages, causing mutations leading to
      carcinogenesis. It has recently become apparent that key proteins which
      contribute to cellular survival by acting in DNA repair become executioners in
      the face of excess DNA damage. Five major DNA repair pathways are homologous
      recombinational repair (HRR), non-homologous end joining (NHEJ), nucleotide
      excision repair (NER), base excision repair (BER) and mismatch repair (MMR). In
      each of these DNA repair pathways, key proteins occur with dual functions in DNA
      damage sensing/repair and apoptosis. Proteins with these dual roles occur in: (1)
      HRR (BRCA1, ATM, ATR, WRN, BLM, Tip60 and p53); (2) NHEJ (the catalytic subunit
      of DNA-PK); (3) NER (XPB, XPD, p53 and p33(ING1b)); (4) BER (Ref-1/Ape, poly(ADP
      ribose) polymerase-1 (PARP-1) and p53); (5) MMR (MSH2, MSH6, MLH1 and PMS2). For
      a number of these dual-role proteins, germ line mutations causing them to be
      defective also predispose individuals to cancer. Such proteins include BRCA1,
      ATM, WRN, BLM, p53, XPB, XPD, MSH2, MSH6, MLH1 and PMS2.

PMID- 12052433
TI  - Forelimb muscle activity following nerve graft repair of ventral roots in the rat
      cervical spinal cord.
AB  - Current research on the cellular mechanisms of nerve regeneration suggests the
      application of nerve growth factors at the repair sites to be beneficial. To test
      the effectiveness of this approach, we performed transections of the C6 and C7
      ventral rootlets from their original sites in the spinal cord of 18 rats. We
      investigated the electrophysiological changes in three groups of rats operated on
      by different repair strategies. Six rats comprised the control group (G1). In the
      other 12 rats, 24 rootlets were implanted into the spinal cord by means of an
      intercostal nerve graft through the pia mater immediately after transection. Six
      rats (G2) had fibrin glue applied at the incision. The last 6 rats (G3) had
      grafts with acidic fibroblast growth factor (aFGF) added to the fibrin glue. The
      rats' functional recovery was evaluated electrophysiologically at 6 weeks and 6
      months after the operation. Needle electromyography showed profound fibrillation
      potentials (Daube's scoring system) in the deltoid, biceps, and triceps of the
      operated forelimbs in all groups 6 weeks after the operation. After 6 months,
      there was a significant decrease in the amount of fibrillation potentials in all
      groups (G1, G2 and G3, p < 0.0001, 0.0001, 0.0009, respectively, generalized
      estimating equation, repeated measures) and a significantly high probability for
      motor units present in sampled muscles of G2 and G3 as compared to G1 (log odds
      ratio in G2 = 51.8316, G3 = 57.4262, generalized estimating equation). We
      conclude that several cervical roots can regenerate through intercostal nerve
      grafts applied using fibrin glue. Adding aFGF may increase the efficacy of
      sprouting.

PMID- 12052434
TI  - Effects of papaya seed extract and benzyl isothiocyanate on vascular contraction.
AB  - To investigate their potentially toxic effects on mammalian vascular smooth
      muscle, pentane extracts of papaya seeds and the chief active ingredient in the
      extracts, benzyl isothiocyanate (BITC), were tested for their effects on the
      contraction of strips of dog carotid artery. BITC and the papaya seed extract
      caused relaxation when added to tissue strips that had been pre-contracted with
      phenylephrine (PE). Incubation of the tissue with papaya seed extract or BITC
      caused inhibition of contraction when the strips were subsequently contracted
      with KCl or PE. This relaxation and inhibition of contraction did not appear to
      be endothelium-dependent, as endothelium-denuded rings showed the same degree of
      relaxation or inhibition of contraction in response to the preparations/drugs as
      those with the endothelium intact. The effects of both BITC and the extract were
      irreversible, i.e., the tissue did not recover to normal contractile ability
      after extensive washing. Exposure of the tissue to the papaya seed extract caused
      slower relaxation of the tissue, compared to controls, both after contraction
      with PE and subsequent addition of carbachol (CCh), and after contraction with
      KCl and then washing. Calcium imaging studies using cultured endothelial cells
      showed strong influxes of Ca2+ into the cells in response to addition of the
      papaya seed extract. We conclude that these extracts, when present in high
      concentration, are cytotoxic by increasing the membrane permeability to Ca2+, and
      that the vascular effects of papaya seed extracts are consistent with the notion
      that BITC is the chief bio-active ingredient.

PMID- 12052435
TI  - Aged garlic extract enhances production of nitric oxide.
AB  - Nitric oxide (NO) controls several physiological functions of the cardiovascular
      system. Three kinds of NO synthases (NOSs), neuronal constitutive NOS (ncNOS),
      inducible NOS (iNOS) and endothelial constitutive NOS (ecNOS), were responsible
      for NO biosynthesis. This study investigated the effect of aged garlic extract
      (AGE) on NO production by measuring the NO metabolites nitrite and nitrate in the
      plasma of mice. AGE (2.86 g/kg, p.o.) temporarily increased NO production by 30
      40% from 15 to 60 min after administration. The time course of the fluctuation in
      NO levels in the AGE-treated group was clearly different to that in a group of
      mice treated with lipopolysaccharides, a typical iNOS inducer. Arginine (63
      mg/kg, p.o.) at the equivalent dose of AGE did not increase NO production.
      However diphenyleneiodonium chloride (1 mg/kg, i.p.), a selective cNOS inhibitor,
      administered prior to AGE, overcame the effect of AGE. These results indicate
      that AGE increased NO production by activating cNOS, but not iNOS. The arginine
      contained in AGE was not responsible for the effect. AGE may be a useful tool for
      the prevention of cardiovascular disease.

PMID- 12052436
TI  - One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze
      is not due to acquisition of a phobic avoidance of open arms during initial
      exposure.
AB  - A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or
      abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called
      one-trial tolerance has been suggested to represent the acquisition of a phobic
      like response to the open arms during trial 1. The present study was designed to
      examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in
      a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a
      four-enclosed arm EPM or a conventional EPM, as well as in naive rats.
      Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of
      time spent on the open arms) in a traditional EPM in naive rats and in animals
      previously exposed to a four-open-arm EPM. However, it was ineffective in rats
      previously exposed to a traditional or a four-closed-arm EPM. Thus, the
      phenomenon of one-trial tolerance does not depend upon initial open-arm
      experience.

PMID- 12052437
TI  - Priming effects of novel nonsteroidal progesterone receptor modulators CP8816 and
      CP8863 on the development of adenomyosis in the mouse uterus.
AB  - The possibility of therapeutic application of novel nonsteroidal progesterone
      receptor modulators CP8816 and CP8863 for preventing the development of uterine
      adenomyosis was investigated in mice. First priming effects of CP8816 on 17beta
      estradiol (E2)-induced cell division in uterine tissues were examined. As a
      result, pretreatment with CP8816 or progesterone significantly suppressed the
      elevation of the mitotic activity in the luminal epithelial cells of mice treated
      with E2 later. Priming with CP8816 had little effect on the stromal cells, but
      progesterone priming caused an increase of stromal mitotic activity in mice
      treated with E2 later. To evaluate the inhibitory effect of these compounds on
      the development of adenomyosis induced experimentally by pituitary grafting, 7
      week-old female mice were isografted with a single anterior pituitary in the
      uterus and divided into four groups. Two groups of mice were given daily
      subcutaneous injections of 1 mg of CP8816 or the vehicle alone for 6 weeks from
      the day after the grafting. Remaining two groups of mice were given oral
      administration of 1 mg of CP8863 or the vehicle only for 5 weeks starting one
      week after the grafting. The incidence of adenomyosis was significantly lower in
      the groups of mice treated with CP8816 and CP8863 than in the respective control
      groups. The mechanism by which CP compounds inhibited the development of
      adenomyosis might be related to their priming effects, i.e., their inhibitory
      effect on epithelial cell division and lack of effect on stromal cell division
      after subsequent exposure to E2.

PMID- 12052438
TI  - Direct measurement of renal sympathetic nervous activity in high-fat diet-related
      hypertensive rats.
AB  - The elevation of renal sympathetic nervous activity (SNA) is a possible cause of
      blood pressure (BP) elevation. Although a high-fat diet (FAT) often induces BP
      elevation in animals, the effect of FAT on renal SNA in animals is not consistent
      between studies. Thus, we compared the basal levels of efferent renal SNA and BP
      in FAT- or high-carbohydrate diet (CHO)-fed rats. Twenty-four male Sprague-Dawley
      rats were fed FAT (P/F/C=20/45/35% cal) or CHO (20/5/75) from 5 weeks of age.
      After 20-21 weeks of feeding, a 24-h urine sample was collected to measure sodium
      excretion. The next day, blood (0.2 ml) was withdrawn from a femoral artery, and
      basal efferent renal nerve discharges and mean arterial pressure (MAP) were
      recorded under anesthesia. Immediately after the experiment, abdominal
      (epididymal, perirenal and mesenteric) adipose tissues were dissected. Total
      abdominal fat weight was significantly greater in the FAT group than in the CHO
      group. The plasma level of leptin was significantly higher in the FAT group, but
      blood glucose and plasma insulin levels did not differ between the two groups.
      MAP and renal SNA were significantly higher in the FAT group. In addition, the
      ratio of urinary sodium excretion to dietary sodium intake was significantly
      lower in the FAT group than in the CHO group. The data suggest that the increased
      renal SNA may contribute to BP elevation in FAT-fed rats. The present study
      firstly demonstrated that renal SNA was elevated with FAT-related BP elevation.

PMID- 12052439
TI  - Protease-activated receptor-2-mediated Ca2+ signaling in guinea pig tracheal
      epithelial cells.
AB  - The protease-activated receptor-2 (PAR-2), a G protein-coupled receptor activated
      by trypsin, contributes to the pathogenesis of inflammatory disease including
      asthma. Here, we examined the mechanisms by which stimulation of PAR-2 induces an
      increase in intracellular Ca2+ concentration ([Ca2+]i) in guinea pig tracheal
      epithelial cells. Trypsin (0.01-3 units/ml) dose-dependently induced a transient
      increase in [Ca2+]i, the increase being blocked by soybean trypsin inhibitor
      (SBTI 1 microM). An increase in [Ca2+]i was also induced by an agonist peptide
      for PAR-2 (SLIGRL-NH2, 0.001-10 microM) but not by thrombin (3 units/ml, an
      activator for PAR-1, PAR-3 or PAR-4). Repeated or cross stimulation of trypsin or
      SLIGRL-NH2 caused marked desensitization of the [Ca2+]i response. These responses
      of [Ca2+]i to trypsin and SLIGRL-NH2 were attenuated by a phospholipase C
      inhibitor, U-73122, and a Ca2+-ATPase inhibitor, thapsigargin (100 nM), while
      removal of Ca2+ and a L-type Ca2+-channel blocker, verapamil, were without
      significant effects. Further, trypsin was without effect on the rate of fura 2
      quenching by Mn2+ entry as an indicator of Ca2+ influx. Thus, stimulation of PAR
      2 appears to increase [Ca2+]i through the mobilization of Ca2+ from intracellular
      stores probably via phospholipase Cbeta-linked generation of a second messenger.

PMID- 12052440
TI  - Cytoprotective effects of calbindin-D(28k) against antimycin-A induced hypoxic
      injury in proximal tubular cells.
AB  - Intracellular calcium plays an important role on the pathogenesis of hypoxia
      induced cellular injury. Calbindin-D(28k), a cytosolic vitamin D-dependent
      calcium binding protein, can serve as a buffer to limit a surge in intracellular
      Ca2+ concentration ([Ca2+]i) induced by various stimulations. To evaluate the
      possible cytoprotective effect of calbindin-D(28k) against hypoxic injury in
      proximal tubular cells, a plasmid containing calbindin-D(28k) cDNA under the
      control of CMV immediate-early gene promoter was transfected into the murine
      proximal tubular epithelial (MCT) cells. The expression of calbindin-D(28k) in
      the transfected cells was verified with Northern blot analysis, Western blot
      analysis, and immunofluorescent staining. The non-transfected and transfected MCT
      cells were subjected to chemical hypoxia induced by antimycin A (10 microM) and
      glucose deprivation for 30-120 min. The transfection of calbindin-D(28k) reduced
      lactate dehydrogenase (LDH) release by 41%, 41%, 24%, and 24%, respectively, at
      30, 60, 90 and 120 min after hypoxia when compared to the non-transfected cells
      (all p < 0.05). Cell viability after hypoxic injury was also significantly higher
      in transfected cells than non-transfected cells. Transfection with the plasmid
      without calbindin-D(28k) cDNA did not affect LDH release or cell viability after
      chemical hypoxic injury. [Ca+2]i was measured ratiometrically with fura-2 after
      exposure to chemical hypoxia. The rate of initial rise in [Ca2+]i and final
      [Ca+2]i at 30-120 min were significantly lowered in transfected cells. In
      conclusion, this study demonstrated that transfection of calbindin-D(28k) gene
      into MCT cells provide protective effects against chemical hypoxic injury
      probably through its buffering effects on [Ca+2]i.

PMID- 12052441
TI  - Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like
      immunoreactivity in the rat spinal cord via activation of endogenous opioid
      systems.
AB  - We investigated the antagonism of sevoflurane antinociception by opioid
      antagonists in the rat formalin test. Formalin injection into the hindpaw of the
      rat induces the nocifensive flinching behavior and the expression of Fos-like
      immunoreactivity (Fos-LI) in the spinal cord. Sevoflurane significantly
      suppressed the flinching behavior and decreased the number of Fos-LI neurons in
      the dorsal horn of spinal cord compared with the control group. Moreover,
      pretreatment with intraperitoneal naloxone plus naltrexone antagonized the
      suppression of flinching behavior and the decrease of the number of Fos-LI
      neurons produced by 3% sevoflurane. Intraperitoneal opioid antagonists themselves
      had no effects on both the behavior response and the expression of Fos-LI induced
      by formalin injection. This study supports the hypothesis that sevoflurane
      suppresses the nociceptive response, at least in part, by activating endogenous
      opioid systems.

PMID- 12052442
TI  - Mitochondrial calcium response in human transformed lymphoblastoid cells.
AB  - Human lymphoblastoid cell line (LCL) transformed by Epstein-Barr Virus (EBV) is a
      unique cellular model for the study of human diseases. Although
      pathophysiological significance of mitochondrial calcium regulation is drawing
      attention, it is not known whether or not mitochondria in LCLs play a role in
      intracellular calcium signaling. In this study, role of mitochondria of the
      lymphoblastoid cell line in calcium signaling was examined. Intra-mitochondrial
      calcium concentration ([Ca2+]m) was successfully measured using dihydro-Rhod-2,
      revealed by the decrease of fluorescence after application of carbonyl cyanide m
      chlorophenylhydrazone (CCCP) and intracellular localization patterns imaged by
      fluorescent microscope. Platelet activating factor (PAF) concentration
      dependently increased cytosolic calcium concentration ([Ca2+]i), while no
      increase of [Ca2+]m was observed. In contrast, 10 microM thapsigargin increased
      [Ca2+]i as well as [Ca2+]m. LCLs may be used for the study of possible
      pathophysiological role of mitochondrial calcium regulation in human diseases.

PMID- 12052443
TI  - Protection of cultured rat cortical neurons from excitotoxicity by asarone, a
      major essential oil component in the rhizomes of Acorus gramineus.
AB  - Previous reports have shown that the methanol extract and the essential oil from
      Acori graminei Rhizoma (AGR) inhibited excitotoxic neuronal cell death in primary
      cultured rat cortical cells. In the present study, an active principle was
      isolated from the methanol extract by biological activity-guided fractionations
      and identified as asarone. We evaluated neuroprotective actions and action
      mechanisms of the isolated asarone as well as the alpha- and the beta-asarone
      obtained commercially. The isolated asarone inhibited the excitotoxicity induced
      by the exposure of cortical cultures for 15 min to 300 microM NMDA in a
      concentration-dependent manner, with the IC50 of 56.1 microg/ml. The commercially
      obtained alpha- and beta-asarone exhibited more potent inhibitions of the NMDA
      induced excitotoxicity than the isolated asarone. Their respective IC50 values
      were 18.2 and 26.5 microg/ml. The excitotoxicity induced by glutamate (Glu) was
      also inhibited, but with much less potency than the toxicity induced by NMDA. The
      IC50 values for the alpha-, beta-, and the isolated asarone were 89.7, 121.7, and
      279.5 microg/ml, respectively. Based on the receptor-ligand binding studies using
      a use-dependent NMDA receptor-channel blocker [3H]MK-801, asarone inhibited the
      specific bindings in a concentration-dependent fashion. These results indicate
      that asarone, the major essential oil component in AGR, exhibits neuroprotective
      action against the NMDA- or Glu-induced excitotoxicity through the blockade of
      NMDA receptor function. The alpha-asarone was found to exhibit more potent
      inhibition of [3H]MK-801 bindings, which is consistent with its more potent
      neuroprotective action than the beta- or the isolated asarone.

PMID- 12052445
TI  - Misconceptions (2): turnover is always higher in cancellous than in cortical
      bone.

PMID- 12052444
TI  - Exercise training increases membrane bound form of tumor necrosis factor-alpha
      receptors with decreases in the secretion of soluble forms of receptors in rat
      adipocytes.
AB  - We examined the effects of exercise training (treadmill running over 9 weeks) on
      the ability of isolated adipocytes to secrete tumor necrosis factor-alpha (TNF
      alpha) and type 1 soluble TNF receptor (sTNFR1) in vitro in Wistar rats. We also
      examined the effects of exercise training on the expression of membrane bound
      forms of type 1 TNF receptor (mTNFR1) in adipocyte crude membranes of the same
      rat subjects. Exercise training significantly increased the secretions of TNF
      alpha from isolated adipocytes. Treatment with a cyclooxygenase inhibitor, either
      indomethacin (100 microM) or eicosatetraynoic acid (100 microM), significantly
      blocked the release of TNF-alpha from adipocytes in both exercise-trained rat
      group and sedentary control rat group, suggesting that some cyclooxygenase
      metabolite(s) acts as a ligand in TNF-alpha synthesis. Decreased amounts of TNF
      alpha were found to be significantly greater in both exercise-trained rat group
      than in sedentary control rat group after incubation with inhibitors. Thus, the
      inhibitory effect of both indomethacin and eicosatetraynoic acid was
      significantly greater in adipocytes from exercise-trained rats. Both plasma
      sTNFR1 levels and adipocytes-derived sTNFR1 were found to be significantly less
      in the exercise-trained rat group. Western blot analysis revealed that exercise
      training remarkably increased the expressions of mTNFR1 in adipocyte crude
      membrane. Thus, exercise training enhanced the ability of isolated adipocytes to
      secrete TNF-alpha with reduced secretion of sTNFR1, and provoked the greater
      expressions of mTNFR1 in adipocyte crude membrane. These alterations may induce
      enhanced the autocrine effects of TNF-alpha within adipocytes in exercise-trained
      rats.

PMID- 12052446
TI  - The potential of biomimesis in bone tissue engineering: lessons from the design
      and synthesis of invertebrate skeletons.
AB  - Synthetic bone replacement materials are now widely used in orthopedics. However,
      to date, replication of trabecular bone structure and mechanical competence has
      proved elusive. Maximization of bone tissue attachment to replacement materials
      requires a highly organized porous structure for tissue integration and a
      template for assembly, combined with structural properties analogous to living
      bone. Natural structural biomaterials provide an abundant source of novel bone
      replacements. Animal skeletons have been designed through optimization by natural
      selection to physically support and physiologically maintain diverse tissue types
      encompassing a variety of functions. These skeletons possess structural
      properties that provide support for the complete reconstruction and regeneration
      of ectodermal, mesodermal, and bone tissues derived from animal and human and are
      thus suited to a diversity of tissue engineering applications. Increased
      understanding of biomineralization has initiated developments in biomimetic
      synthesis with the generation of synthetic biomimetic materials fabricated
      according to biological principles and processes of self-assembly and self
      organization. The synthesis of complex inorganic forms, which mimic natural
      structures, offers exciting avenues for the chemical construction of
      macrostructures and a new generation of biologically and structurally related
      bone analogs for tissue engineering.

PMID- 12052447
TI  - Bone morphogenetic protein-2 coating of titanium implants increases biomechanical
      strength and accelerates bone remodeling in fracture treatment: a biomechanical
      and histological study in rats.
AB  - Bone morphogenetic protein-2 (BMP-2), a member of the transforming growth factor
      (TGF)-beta superfamily, is known to be a very potent osteoinductive growth
      factor. The purpose of this study was to investigate the effect of BMP-2 (5%
      [w/w], 50 microg on each nail), locally released from poly(D,L-lactide) (PDLLA)
      coated intramedullary implants, on fracture healing. A closed fracture of the
      right tibia of 5-month-old Sprague-Dawley rats (n = 64) was intramedullary
      stabilized with uncoated vs. BMP-2-coated titanium Kirschner wires. X-ray
      examinations (posteroanterior and lateral) were performed throughout the
      experiment. At 28 and 42 days after fracture, the animals were killed and both
      tibiae were dissected for biomechanical torsional testing. For histological and
      histomorphometric evaluation, 5 microm sections were obtained, stained with
      Safranin-O/light green and von Kossa, and examined using an image analysis
      system. The radiological results demonstrated progressed callus consolidation in
      the BMP-2-treated groups compared with the uncoated groups at both timepoints.
      Histomorphometric evaluation showed progressed callus remodeling with
      significantly increased mineralization and less cartilage of the periosteal
      callus. Due to the BMP-2 treatment, increased mineralization of the cortices was
      detected at 28 and 42 days after fracture. Biomechanical testing revealed
      significantly elevated maximum load and torsional stiffness in the BMP-2-treated
      groups compared with controls at both timepoints. The results clearly demonstrate
      that local application of BMP-2 from PDLLA-coated implants is feasible and
      significantly accelerates fracture healing. Local administration of growth
      factors from coated implants could reduce clinical problems in fracture treatment
      without opening of the fracture, implantation of further devices, or injection
      with the risk of infection or side effects caused by other carriers.

PMID- 12052448
TI  - Human fetal bone development: histomorphometric evaluation of the proximal
      femoral metaphysis.
AB  - Quantitative data on metaphyseal bone histology during early human development
      are scarce. In the present study the proximal femoral metaphysis of 35 fetuses
      and newborns (gestational age 16-35 weeks) was analyzed by histomorphometry.
      Averaged over the entire metaphyseal area, the relative amount of bone and
      cartilage was higher in the third compared to the second trimester. Osteoid
      thickness increased with gestational age, whereas indices of bone resorption
      decreased. The relative amount of cartilage decreased with increasing distance
      from the growth plate, whereas the relative amount of bone increased. This was
      due to trabecular thickening, which occurred at an estimated rate of 3 microm/day
      in areas close to the growth plate. Despite this rapid rate of net bone gain,
      osteoid indices were relatively low, indicating that mineralization occurred very
      rapidly after bone deposition. These observations suggest that modeling, not
      remodeling, is the predominant mechanism responsible for the development of
      femoral metaphyseal cancellous bone in utero.

PMID- 12052449
TI  - Patient-specific microarchitecture of vertebral cancellous bone: a peripheral
      quantitative computed tomographic and histological study.
AB  - This study directly compares peripheral quantitative computed tomography (pQCT)
      and histology for the assessment of 11 morphological parameters. Sixty-eight
      cylindrical cancellous bone samples were cored from the thoracic (T-9)
      thoracolumbar (T-12 or L-1), and lumbar (L-4) vertebral bodies of nine autopsy
      subjects (aged 44-88 years). Four transverse slices were acquired by pQCT from
      the bottom to the top of each cylinder. Slice thickness was 300 microm and pixel
      size was 70 x 70 microm. Thin sections (5 microm) were obtained at the same
      location in the samples, stained with Von Kossa, and photographed. Classical
      morphological parameters and strut analysis parameters were measured on all
      images (272 pQCT and 272 matched histological sections). Because of the partial
      volume effect and specific thresholding procedure, pQCT overestimated the
      absolute value of the bone volume fraction (BV/TV) and trabecular thickness
      (Tb.Th) by a factor 2. The trabecular number (Tb.N), trabecular spacing (Tb.Sp),
      and total strut length (TSL) were correctly estimated. However, the direct
      correlation between pQCT and histology was excellent (r2 > 0.85, p < 0.001) for
      BV/TV, Tb.N, Tb.Sp, TSL, and star surface. For Tb.Th, number of nodes, and number
      of free ends, the correlation was also good (r(2) > 0.6, p < 0.001). Using a
      random regression model, we also explored the ability of these parameters to add
      structural information to the readily available BV/TV or apparent density. The
      model identified significant (p < 0.001) differences between subjects. For a
      given BV/TV, some patients had more trabeculae (Tb.N) that were thinner (Tb.Th)
      and more disconnected (higher free ends and star). This was observed for both
      histology and pQCT morphometrical data. Our analysis demonstrates the capacity of
      both histology and pQCT to detect subjects with specific structural patterns in
      vertebral cancellous bone.

PMID- 12052450
TI  - Stronger back muscles reduce the incidence of vertebral fractures: a prospective
      10 year follow-up of postmenopausal women.
AB  - The long-term protective effect of stronger back muscles on the spine was
      determined in 50 healthy white postmenopausal women, aged 58-75 years, 8 years
      after they had completed a 2 year randomized, controlled trial. Twenty-seven
      subjects had performed progressive, resistive back-strengthening exercises for 2
      years and 23 had served as controls. Bone mineral density, spine radiographs,
      back extensor strength, biochemical marker values, and level of physical activity
      were obtained for all subjects at baseline, 2 years, and 10 years. Mean back
      extensor strength (BES) in the back-exercise (BE) group was 39.4 kg at baseline,
      66.8 kg at 2 years (after 2 years of prescribed exercises), and 32.9 kg at 10
      years (8 years after cessation of the prescribed exercises). Mean BES in the
      control (C) group was 36.9 kg at baseline, 49.0 kg at 2 years, and 26.9 kg at 10
      years. The difference between the two groups was still statistically significant
      at 10 year follow-up (p = 0.001). The difference in bone mineral density, which
      was not significant between the two groups at baseline and 2 year follow-up, was
      significant at 10 year follow-up (p = 0.0004). The incidence of vertebral
      compression fracture was 14 fractures in 322 vertebral bodies examined (4.3%) in
      the C group and 6 fractures in 378 vertebral bodies examined (1.6%) in the BE
      group (chi-square test, p = 0.0290). The relative risk for compression fracture
      was 2.7 times greater in the C group than in the BE group. To our knowledge, this
      is the first study reported in the literature demonstrating the long-term effect
      of strong back muscles on the reduction of vertebral fractures in estrogen
      deficient women.

PMID- 12052451
TI  - Estimation of distal radius failure load with micro-finite element analysis
      models based on three-dimensional peripheral quantitative computed tomography
      images.
AB  - There is increasing evidence that, in addition to bone mass, bone
      microarchitecture and its mechanical load distribution are important factors for
      the determination of bone strength. Recently, it has been shown that new high
      resolution imaging techniques in combination with new modeling algorithms based
      on the finite element (FE) method can account for these additional factors. Such
      models thus could provide more relevant information for the estimation of bone
      failure load. The purpose of the present study was to determine whether results
      of whole-bone micro-FE (microFE) analyses with models based on three-dimensional
      peripheral quantitative computer tomography (3D-pQCT) images (isotropic voxel
      resolution of 165 microm) could predict the failure load of the human radius more
      accurately than results with dual-energy X-ray absorptiometry (DXA) or bone
      morphology measurements. For this purpose, microFE models were created using 54
      embalmed cadaver arms. It was assumed that bone failure would be initiated if a
      certain percentage of the bone tissue (varied from 1% to 7%) would be strained
      beyond the tissue yield strain. The external force that produced this tissue
      strain was calculated from the FE analyses. These predictions were correlated
      with results of real compression testing on the same cadaver arms. The results of
      these compression tests were also correlated with results of DXA and structural
      measurements of these arms. The compression tests produced Colles-type fractures
      in the distal 4 cm of the radius. The predicted failure loads calculated from the
      FE analysis agreed well with those measured in the experiments (R(2) = 0.75 p <
      0.001). Lower correlations were found with bone mass (R(2) = 0.48, p < 0.001) and
      bone structural parameters (R(2) = 0.57 p < 0.001). We conclude that application
      of the techniques investigated here can lead to a better prediction of the bone
      failure load for bone in vivo than is possible from DXA measurements, structural
      parameters, or a combination thereof.

PMID- 12052452
TI  - Lack of association between calcium-sensing receptor gene "A986S" polymorphism
      and bone mineral density in Hungarian postmenopausal women.
AB  - Calcium-sensing receptor (CaSR) is an attractive candidate gene for osteoporosis
      susceptibility. The CaSR "A986S" genotype has been shown to have an effect on
      serum calcium. Recently, an association has been reported between the CaSR gene
      A986S polymorphism and bone mineral density in healthy white girls. In this
      study, we examined whether CaSR gene A986S polymorphism is associated with
      decreased bone mass in 230 Hungarian postmenopausal women. From this cohort, 108
      osteoporotic patients were compared with 122 healthy control women. Bone mineral
      density (BMD) was measured at the lumbar spine (L2-4) and femoral neck using dual
      energy X-ray absorptiometry. Allele-specific polymerase chain reaction was used
      to amplify A986S polymorphisms of the CaSR gene. We found no difference in the
      distribution of different alleles or genotypes between groups (p = 0.762). No
      significant effect of CaSR genotype on BMD was observed either in the whole
      population or in the subgroups. Our data do not support the idea that CaSR gene
      A986S polymorphism has an impact on bone mass.

PMID- 12052453
TI  - Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid
      treatment in patients with chronic glomerulonephritis.
AB  - It is well known that long-term glucocorticoid treatment causes osteoporosis, but
      the precise mechanism remains unclear. Recently, osteoprotegerin (OPG) has been
      identified as a cytokine that inhibits osteoclast differentiation. We have
      previously demonstrated that serum OPG is suppressed by glucocorticoids.
      Therefore, the present study was carried out to clarify the interrelationships
      between OPG and other markers of bone metabolism during glucocorticoid treatment.
      Thirteen patients (7 men, 6 women; 44.1 +/- 5.9 years old) with chronic
      glomerulonephritis who were to be treated with glucocorticoids for the first time
      were chosen for this study. Markers of bone metabolism, including serum OPG,
      osteocalcin (OC), bone-specific alkaline phosphatase activity (bAP), parathyroid
      hormone (PTH), tartrate-resistant acid phosphatase (TRAP), and bone mineral
      density (BMD), were measured before and during the treatment period.
      Glucocorticoids significantly reduced BMD of the lumbar spine in the 6 month
      treatment period (p < 0.01). Serum OPG was decreased significantly by
      glucocorticoids within 2 weeks (p < 0.001), and serum TRAP, a marker of bone
      resorption, was markedly increased (p < 0.001). On the other hand, there were no
      remarkable changes in serum PTH. Serum OC and bAP, markers of bone formation,
      were transiently reduced during the treatment period (p < 0.01). Furthermore,
      only serum OPG was positively and independently correlated with percentage BMD of
      age-matched reference (%AMR). These findings imply that glucocorticoid-induced
      bone loss develops rapidly via enhanced bone resorption and suppressed bone
      formation. Moreover, the increased bone resorption caused by glucocorticoids may
      be, at least in part, mediated by inhibition of OPG, not increment of PTH.

PMID- 12052454
TI  - Osteocyte density in aging subjects is enhanced in bone adjacent to remodeling
      haversian systems.
AB  - The osteocyte is a candidate regulatory cell for bone remodeling. Previously, we
      demonstrated that there is a substantial (approximately 50%) loss of osteocytes
      from their lacunae in the cortex of the elderly femoral neck. Higher occupancy
      was evident in tissue exhibiting high remodeling and high porosity. The present
      study examines the distribution of osteocytes within individual osteonal systems
      at differing stages of the remodeling cycle. In 22 subjects, lacunar density,
      osteocyte density, and their quotient, the percent lacunar occupancy, was
      assessed up to a distance of 65 microm from the canal surface in six quiescent,
      resorbing, and forming osteons. In both forming (p = 0.024) and resorbing (p =
      0.034) osteons, osteocyte densities were significantly higher in cases of hip
      fracture than controls. However, there were no significant between-group
      differences in lacunar occupancy. In both cases and controls, osteocyte density
      (p < 0.0001; mean difference +/-SEM: 157 +/- 34/mm2) and lacunar occupancy (p =
      0.025; mean difference: 8.1 +/- 3.4%) were shown to be significantly higher in
      forming compared with quiescent osteons. Interestingly, resorbing systems also
      exhibited significantly elevated osteocyte density in both the fracture and the
      control group combined (mean difference 76 +/- 23/mm2; p = 0.003). Lacunar
      occupancy was also greater in resorbing compared with quiescent osteons (both
      groups combined: p = 0.022; mean difference: 5.7 +/- 2.3%). Elevated osteocyte
      density and lacunar occupancy in forming compared with quiescent systems was
      expected because of the likely effects of aging on quiescent osteons. However,
      the higher levels of these parameters in resorbing compared with quiescent
      systems was the opposite of what we expected and suggests that, in addition to
      their postulated mechanosensory role in the suppression of remodeling and bone
      loss, osteocytes might also contribute to processes initiating or maintaining
      bone resorption.

PMID- 12052455
TI  - Patterns of osteocytic endothelial nitric oxide synthase expression in the
      femoral neck cortex: differences between cases of intracapsular hip fracture and
      controls.
AB  - Evidence indicates that extensive amalgamation of adjacent resorbing osteons is
      responsible for destroying the microstructural integrity of the femoral neck's
      inferior cortex in osteoporotic hip fracture. Such osteonal amalgamation is
      likely to involve a failure to limit excessive resorption, but its mechanistic
      basis remains enigmatic. Nitric oxide (NO) inhibits osteoclastic bone
      destruction, and in normal bone cells its generation by endothelial nitric oxide
      synthase (eNOS, the predominant bone isoform) is enhanced by mechanical stimuli
      and estrogen, which both protect against fracture. To determine whether eNOS
      expression in osteocytes reflects their proposed role in regulating remodeling,
      we have examined patterns of osteocyte eNOS immunolabeling in the femoral neck
      cortex of seven cases of hip fracture and seven controls (females aged 68-96
      years). The density of eNOS+ cells (mm(-2)) was 53% lower in the inferior cortex
      of the fracture cases (p < 0.0004), but was similar in the superior cortex. eNOS+
      osteocytes were, on average, 22% further from their nearest blood supply, than
      osteocytes in general (p < 0.0001) and the nearest eNOS+ osteocyte was 57%
      further from its nearest canal surface (p < 0.0001). This differential
      distribution of eNOS+ osteocytes was significantly more pronounced in the
      cortices of fracture cases (p < 0.0001). We conclude that the normal regional and
      osteonal pattern of eNOS expression by osteocytes is disrupted in hip fracture,
      particularly at sites that are loaded most by physical activity. These results
      suggest that eNOS+ osteocytes may normally act as sentinels confining resorption
      within single osteons. A reduction in their number, coupled to an increase in
      their remoteness from canal surfaces, may thus permit the irreversible merging of
      resorbing osteons, and thus contribute to the marked increase in the fragility of
      osteoporotic bone.

PMID- 12052456
TI  - Stage-dependent changes in trabecular bone turnover and osteogenic capacity of
      marrow cells during development of type II collagen-induced arthritis in mice.
AB  - Rheumatoid arthritis (RA) is a disease characterized by inflammatory
      polyarthritis leading to destruction of the joints and reduction in bone mass.
      However, the relationship between bone mass and turnover is not yet clear in RA
      patients. To clarify the effect of bone turnover and marrow osteogenic capacity
      on mass and structure during the development of arthritis, we examined DBA1/J
      mice for 8 weeks after the first immunization with bovine type II collagen at the
      age of 9 weeks. Localized arthritis developed at 4 weeks and advanced arthritis
      at 6 weeks postimmunization. Urinary deoxypyridinoline levels in arthritic mice
      were significantly higher at 4 weeks, and levels were maintained thereafter.
      Their serum osteocalcin levels were significantly reduced compared with controls
      at 2 and 6 weeks, but did not differ significantly from those in the control
      group at 4 and 8 weeks. Three-dimensional (3D) trabecular bone volume of the
      proximal tibia measured by 3D microcomputed tomography (micro-CT) in the
      arthritic mice became significantly lower at 4 weeks and decreased further at 6
      weeks compared with controls. Parameters of 3D trabecular bone structure, such as
      structure model index and trabecular bone pattern factor, were increased at 4 and
      6 weeks, respectively. Trabecular osteoclast number increased and bone formation
      rates decreased at 8 weeks. The number of total bone marrow cells (BMCs),
      adherent stromal cells, and area of mineralized nodule formation in the tibia of
      arthritic mice were significantly reduced compared with controls at 6 weeks.
      Numbers of total fibroblastic colony-forming units (CFU-f) and alkaline
      phosphatase (ALP)-positive CFU-f colonies also decreased. However, the values of
      these osteogenic parameters corrected for the total BMCs and/or adherent stromal
      cells did not differ significantly between the arthritic and control groups.
      These data indicate that an increase in bone resorption led to the reduction in
      trabecular bone mass and deterioration of 3D structure during the localized
      arthritic stage. The reduction in bone marrow osteogenic potential in the
      advanced arthritic stage was due to the reduction in the number of total bone
      marrow cells, and differentiation of osteogenic cells was apparently unaffected.
      The reduction in bone formation may not be substantial in this arthritic model.

PMID- 12052457
TI  - Overexpression of granulocyte colony-stimulating factor induces severe osteopenia
      in developing mice that is partially prevented by a diet containing vitamin K2
      (menatetrenone).
AB  - Mice transgenic for granulocyte colony-stimulating factor (G-CSF) exhibit severe
      osteopenia with an increase of osteoclast number and acceleration of bone
      resorption in adult mice. To examine the effect of G-CSF overexpression on
      developing bone, bone mineral density levels were examined from 4 weeks through
      36 weeks after birth. Peak bone mass was observed at around 24 weeks of age
      irrespective of G-CSF expression. Apparent osteopenia was observed as early as 4
      weeks of age without detectable developmental retardation in bone length and
      skeletal structure. Morphological examination confirmed a reduction of cancellous
      bone and cortical bone at this early stage of life, indicating that
      overexpression of G-CSF results in apparent osteopenia in developing mice,
      similar to that in adult animals. The effect of vitamin K2 (menatetrenone) (MK4)
      on bone phenotypes during development was then examined. Mice were fed chow
      containing either 0.05 mg MK-4 per 100 g or 20.0 mg MK-4 per 100 g for 12 weeks
      as the control and experimental diets, respectively. This treatment did not
      change bone length, irrespective of the type of mouse or diet. Peripheral
      quantitative computed tomography (pQCT) revealed an increase of in CT value bone
      of MK4-treated mice. Taken together, these results indicate that overexpression
      of G-CSF induces an apparent reduction of bone mass and results in osteopenia in
      developing mice. The bone reduction was partially restored by feeding the mice
      MK4, suggesting a choice for treatment on the osteopenia induced by G-CSF.

PMID- 12052458
TI  - Effect of feeding on bone turnover markers and its impact on biological
      variability of measurements.
AB  - Bone turnover markers are subject to day-to-day and within-day variability, which
      may influence clinical interpretation. We examined the effect of fasting vs.
      feeding on the concentration and between-day variability of several markers.
      Twenty healthy premenopausal women were studied on 10 consecutive weekdays.
      Subjects were studied either in the fasting (no breakfast) or fed (breakfast at
      08:00 h) state on alternate days, and were randomized to begin either fasting or
      fed. Two hour urine collections were obtained each day between 08:00 h and 10:00
      h, and blood samples were collected daily at 09:00 h. The N-telopeptide cross
      link of type I collagen in urine (uNTX) and serum (sNTX), the C-telopeptide in
      urine (uCTX) and serum (sbetaCTX), and immunoreactive free deoxypyridinoline
      (uifDPD) in urine were measured as resorption markers. Procollagen type I N
      terminal propeptide (PINP), osteocalcin (OC), and bone alkaline phosphatase (bone
      ALP) were measured as formation markers. All bone formation and resorption
      markers were significantly lower in the fed state with the exception of bone ALP.
      The magnitude of the decrease ranged from 3.8 +/- 0.9% for PINP (p < 0.0001) to
      17.8 +/- 2.6% (p < 0.0001) for sbetaCTX. Measurement variability was partitioned
      into analytical variability based on replicate assays (CV(a)) and within-subject
      variability (CV(i)). The CV(i) was greater (p < 0.05) for some markers in the
      fasting state (uifDPD, uNTX, and sNTX) but greater in the fed state for other
      markers (OC and sbetaCTX). In conclusion, the clinical impact of feeding vs.
      fasting is small with the exception of sbetaCTX; however, in clinical practice,
      collection of samples in the fasting state may be necessary to minimize the
      unpredictable effects of feeding. The mechanism of the acute effect of feeding on
      bone turnover remains uncertain.

PMID- 12052459
TI  - Gender differences in expression of androgen receptor in tibial growth plate and
      metaphyseal bone of the rat.
AB  - In this study, we investigate the expression of the androgen receptor (AR) in the
      tibial growth plate and metaphyseal bone of male and female rats at the mRNA and
      protein level. Using in situ hybridization and immunohistochemistry, AR mRNA and
      protein were demonstrated in proliferating and early hypertrophic chondrocytes in
      the growth plate of 1-, 4-, and 7-week-old male and female rats. Immunostaining
      for AR was observed both in the nucleus and the cytoplasm. After sexual
      maturation at 12 and 16 weeks of age, AR expression decreased in both genders and
      was confined to a small rim of prehypertrophic chondrocytes. In female rats of 40
      weeks of age, this expression pattern was still visible. In most age groups there
      was a tendency toward an increased AR mRNA expression in male vs. female rats
      except in the 7-week-old animals. At the protein level, sexually maturing 7-week
      old male rats demonstrated a higher staining intensity compared to their female
      counterparts. At this stage, AR staining in the males was mainly confined to the
      nucleus, whereas in females staining was predominantly found in the cytoplasm. In
      the tibial metaphysis, AR mRNA was detected in lining cells, osteoblasts,
      osteocytes, and osteoclasts at all stages of development. At the protein level, a
      similar expression pattern was observed, except for an absence of immunostaining
      in the lining cells. The staining was both nuclear and cytoplasmic. In most age
      groups, mRNA and protein signals were higher in males compared with females. We
      have demonstrated the presence of AR mRNA and protein in the tibial growth plate
      and the underlying metaphyseal bone during development of the rat. In male rats,
      the presence of higher messenger and protein staining intensities, as well as
      preferential nuclear staining during sexual maturation, suggests that direct
      actions of androgens in chondrocytes and in bone forming cells may be involved in
      establishing the gender differences in the skeleton.

PMID- 12052461
TI  - Interleukin-18 and interleukin-12 synergistically inhibit osteoclastic bone
      resorbing activity.
AB  - The effect of interleukin (IL)-18 on osteoclastic bone-resorbing activity was
      investigated in vitro. Osteoclast-enriched cells, about 70% of which were
      tartrate-resistant acid phosphatase (TRAP)-positive, were cultured on dentine
      slices, and then the total volume of resorption pits on each dentine slice was
      measured as bone-resorbing activity. When the effects of IL-18 alone at 1, 10,
      100, and 1000 ng/mL were examined, bone-resorbing activity was significantly
      reduced only at 1000 ng/mL, by about 50%. However, IL-18 plus IL-12 (10 ng/mL
      each) reduced bone-resorbing activity by about 70%, whereas IL-12 alone had no
      significant effect. When the concentration of interferon (IFN)-gamma in the
      medium was measured, IL-18 or IL-12 was found to increase it slightly, and the
      combination of these two cytokines synergistically increased it. The inhibitory
      effect of the combination of the two cytokines was completely abolished by the
      addition of an anti-IFN-gamma neutralizing antibody to the medium, but IFN-gamma
      by itself did not inhibit osteoclastic bone resorption. IL-18 alone or in
      combination with IL-12 did not affect the number of TRAP-positive cells in
      culture of osteoclast-enriched cells. Osteoclasts prepared from osteoclast
      enriched cells expressed mRNAs of IL-18 receptor, MyD88, and cathepsin K.
      Furthermore, IL-18 receptor protein was detected on the cell surface of
      osteoclasts. The present results indicate that the combination of IL-18 and IL-12
      synergistically inhibits osteoclastic bone-resorbing activity, suggesting that
      IFN-gamma participates in the mechanism underlying this inhibition.

PMID- 12052460
TI  - Vitamin K supplementation does not affect ovariectomy-induced bone loss in rats.
AB  - Vitamin K may be important in bone metabolism. Notably, high-dose menaquinone-4
      (menatetrenone, MK4) has been reported to reduce ovariectomy (ovx)-induced bone
      loss in rats and to decrease osteoporotic fracture in postmenopausal women.
      However, it is unclear whether these beneficial effects reflect a physiologic
      effect of vitamin K, or indicate direct pharmacologic activity of MK4. To further
      evaluate this, 60 6-month-old nulliparous Sprague-Dawley rats were randomized by
      distal femur bone mineral density (BMD) in a 3:1 ratio to ovx or sham groups. The
      sham and one ovx group's diet contained 1% calcium and 1300 microg/kg of vitamin
      K1, phylloquinone. Diets of the other two ovx groups were supplemented with 882
      mg phylloquinone or MK4 per kilogram chow. Distal femur bone mineral density
      (DFBMD) in an 8 mm region of interest was measured at baseline, 1 and 3 months
      postoperatively, utilizing dual-energy X-ray absorptiometry (DXA). All animals
      were killed at 3 months, their right femurs excised, ex vivo BMD measured by DXA,
      and biomechanical testing performed. No effect of phylloquinone or MK4
      supplementation on ovx-induced bone loss was observed. Specifically, DFBMD
      declined 10.5%, 9.2%, and 11.2% at 1 month and 14.4%, 10.6%, and 13.9% at 3
      months in the ovx control, high phylloquinone, and high MK4 groups, respectively.
      In addition, serum osteocalcin was elevated by ovx; this was not altered by
      phylloquinone or MK4. Finally, femoral biomechanical properties were not affected
      by phylloquinone or MK4. To conclude, in this study, neither high-dose
      phylloquinone nor MK4 reduced the ovx-associated increase in bone turnover or
      decline in DFBMD.

PMID- 12052463
TI  - Polycyclic aromatic hydrocarbons present in cigarette smoke cause bone loss in an
      ovariectomized rat model.
AB  - A number of epidemiological studies have suggested that cigarette smoking is a
      risk factor for osteoporosis. Benzo(a)pyrene (BaP) and 7,12
      dimethylbenz(a)anthracene (DMBA) are polycyclic aromatic hydrocarbons (PAHs)
      found in the tar fraction of cigarette smoke, as well as in car exhaust and
      furnace gases. We hypothesized that BaP and DMBA are responsible, through
      interaction with the aryl hydrocarbon receptor (AhR), for the bone loss and
      fragility seen in smoking-related osteoporosis. In this study four groups of 9
      month-old Sprague-Dawley rats were examined. An intact group served as controls.
      A second control was the ovariectomized (ovx) group. The third group (ovx + E(2))
      were ovariectomized and also given a continuous basal dose of estrogen by
      implanted estrogen pellet (0.085 mg of 17beta-estradiol per rat). The fourth
      group (ovx + E(2) + BaP/DMBA) was ovariectomized with an estradiol pellet, and
      received subcutaneous injections of 250 microg/kg of BaP/DMBA weekly for 15
      weeks. The loss of ovarian function allowed the study of a direct effect of
      BaP/DMBA on bone while the concomitant estrogen repletion prevented ovx-related
      bone loss. Dual-energy X-ray absorptiometry (DEXA), histomorphometry, image
      analysis, and mechanical testing were used to determine the effect of the
      treatments on bone. The DEXA results showed a significant (p < 0.05) decrease in
      bone mineral density compared with intact controls with both ovx alone and with
      ovx + E(2) + BaP/DMBA treatment. The ovx + E(2) rats were similar to the intact
      controls. The osteoid parameters showed a significant increase (p < 0.05) with
      BaP/DMBA addition vs. intact controls, mimicking the ovx rats. The ovx + E(2)
      rats had osteoid parameters comparable to those of intact rats. Bone connectivity
      was decreased in the ovx and ovx + E(2) + BaP/DMBA animals. Connectivity of the
      ovx + E(2) rats was comparable to that of intact animals. A decrease in failure
      force was seen in three-point bending for the ovx + E(2) + BaP/DMBA group and in
      vertebral compression in both the ovx and ovx + E(2) + BaP/DMBA groups vs. intact
      controls. The mechanical properties of the ovx + E(2) rats were similar to those
      of intact rats. These results demonstrate that BaP/DMBA causes a loss of bone
      mass and bone strength, possibly through an increase in bone turnover. This is
      the first in vivo study linking environmental toxicants, found in the tar
      fraction of cigarette smoke and in urban air pollution, to loss of bone mass and
      strength in estrogen-replete ovx rats.

PMID- 12052462
TI  - Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density
      during puberty in IGF-1-deficient MIDI mice.
AB  - Insulin-like growth factor-1 (IGF-1) increases both bone formation and bone
      resorption processes. To test the hypothesis that treatment with an antiresorber
      along with IGF-1, during the pubertal growth phase, would be more effective than
      IGF-1 alone to increase peak bone mass, we used an IGF-1 MIDI mouse model, which
      exhibits a >60% reduction in circulating IGF-1 levels. We first determined an
      optimal IGF-1 delivery by evaluating IGF-1 administration (2 mg/kg body
      weight/day) by either a single daily injection, three daily injections, or by
      continuous delivery via a minipump during puberty. Of the three regimens, the
      three daily IGF-1 injections and IGF-1 through a minipump produced a significant
      increase in total body bone mineral density (BMD) (6.0% and 4.4%, respectively)
      and in femoral BMD (4.3% and 6.2%, respectively) compared with the control group.
      Single subcutaneous (s.c.) administration did not increase BMD. We chose IGF-1
      administration three times daily for testing the combined effects of IGF-1 and
      alendronate (100 microg/kg per day). The treatment of IGF-1 + alendronate for a
      period of 2 weeks increased total body BMD at 1 week and 3 weeks after treatment
      (21.1% and 20.5%, respectively) and femoral BMD by 29% at 3 weeks after
      treatment. These increases were significantly greater than those produced by IGF
      1 alone. IGF-1, but not alendronate, increased bone length. IGF-1 and/or
      alendronate increased both periosteal and endosteal circumference. Combined
      treatment caused a greater increase in the total body bone mineral content (BMC)
      and periosteal circumference compared with individual treatment with IGF-1 or
      alendronate. Our data demonstrate that: (1) inhibition of bone turnover during
      puberty increases net bone density; and (2) combined treatment with IGF-1 and
      alendronate is more effective than IGF-1 or alendronate alone in increasing peak
      bone mass in an IGF-1-deficient MIDI mouse model.

PMID- 12052464
TI  - Glucocorticoid-induced osteopenia in the mouse as assessed by histomorphometry,
      microcomputed tomography, and biochemical markers.
AB  - Glucocorticoids are potent anti-inflammatory molecules used in the treatment of
      asthma, rheumatoid arthritis, inflammatory bowel disease, and other inflammatory
      and dermatological diseases, as well as in posttransplantation immunotherapy.
      Although glucocorticoids have been prescribed for many years, their potential
      side effects, when administered orally, can prevent their long-term use. The most
      serious side effect observed in the clinic is glucocorticoid-induced osteoporosis
      (GIOP). To develop a small animal model to characterize glucocorticoid-induced
      bone loss, we carried out a series of experiments using BALB/c mice given daily
      intraperitoneal doses of the synthetic glucocorticoid, dexamethasone. Following
      dexamethasone treatment, the mice became osteopenic, with highly significant
      decreases in bone formation rate and mineral apposition rate, as assessed by
      standard histomorphometry. Moreover, 3 week treatment with dexamethasone resulted
      in a decrease in trabecular thickness and trabecular number with an increase in
      surface-to-volume ratio of trabeculae in the distal femur, as measured using
      microcomputed tomography (micro-CT). The serum bone formation marker,
      osteocalcin, was dose-dependently decreased in all mice treated with
      dexamethasone and showed a parallel extent of regulation to the bone formation
      rate changes. In addition, serum levels of leptin, recently identified as playing
      a role in the regulation of bone mass, increased following dexamethasone
      treatment. BALB/c mice therefore represent a useful model system in which the
      detrimental effects of glucocorticoids on bone can be studied.

PMID- 12052467
TI  - Genetic polymorphisms: importance for response to HMG-CoA reductase inhibitors.
AB  - Coronary artery disease is among the leading causes of death worldwide. Clinical
      trials show a protective effect of statins against the sequelae of coronary
      artery disease. The mean risk reductions for subjects using statins compared with
      placebo found in these trials is about 30%. These are average reductions for all
      patients included in the trials. Important factors in interpreting the
      variability in the outcome of drug therapy include the patient's health profile,
      prognosis, disease severity, quality of drug prescribing, compliance with
      prescribed pharmacotherapy and the genetic profile of the patient. This review
      aims to give an overview of the known polymorphisms (Cholesteryl Ester Transfer
      Protein polymorphism, Stromelysin-1 polymorphism, -455G/A and TaqI polymorphisms
      of the beta-fibrinogen gene, apoE4, Asp(9)Asn mutation in the lipoprotein lipase
      gene, the -514 CT polymorphism in the hepatic lipase gene and the ACE deletion
      type gene) that have an influence on the effects of statins in the general
      population. The expectation is that in the future a subject's genotype may
      determine whether he will be treated with statins or not. Determining the
      genotype will not deny therapy to a subject, but will help in deciding the
      therapy that will suit the patient best.

PMID- 12052465
TI  - Osteoblast intracellular localization of Nmp4 proteins.
AB  - Nmp4 proteins are transcription factors that contribute to the expression of type
      I collagen and many of the matrix metalloproteinase genes. Numerous Nmp4 isoforms
      have been identified. These proteins, all derived from a single gene, have from
      five to eight Cys(2)His(2) zinc fingers, the arrangement of which directs
      specific isoforms to nuclear matrix subdomains. Nmp4 isoforms also have an SH3
      binding domain, typical of cytoplasmic docking proteins. Although recent evidence
      indicates that Nmp4 proteins also reside in the osteoblast cytoplasm, whether
      they localize to specific organelles or structures is not well defined. The
      intracellular localization of a protein is a determinant of its function and
      provides insights into its mechanism of action. As a first step toward
      determining the functional relationship between the cytoplasmic and nuclear Nmp4
      compartments, we mapped their location in the osteoblast cytoplasm.
      Immunocytochemical analysis of osteoblasts demonstrated that Nmp4 antibodies
      labeled the mitochondria, colocalized with Golgi protein 58K, and lightly stained
      the cytoplasm. Western analysis using Nmp4 antibodies revealed a complex profile
      of protein bands in the nuclear, mitochondrial, and cytosolic fractions. Several
      of these proteins were specific to defined intracellular domains. Consistent with
      the western analyses, reverse transcription-polymerase chain reaction (RT-PCR)
      analysis detected previously uncharacterized Nmp4 isoforms. These data
      necessarily enlarge the known Nmp4 family from nuclear matrix transcription
      factors to a more widely extended class of intracellular proteins.

PMID- 12052468
TI  - The expression of extracellular-superoxide dismutase is increased by
      lysophosphatidylcholine in human monocytic U937 cells.
AB  - Extracellular-superoxide dismutase (EC-SOD) [EC 1.15.1.1] is a secretory
      glycoprotein with an affinity for heparin-like proteoglycans. This enzyme locates
      in blood vessel walls at high levels and may be important for the antioxidant
      capability of vascular walls. Oxidative process plays an important role in
      atherogenesis. Lysophosphatidylcholine (lysoPC) is generated during oxidation of
      low-density lipoprotein (LDL) and is located within atherosclerotic plaques.
      Recently, lysoPC has been reported to induce transcription of a variety of
      cellular genes. In this study, we observed that lysoPC significantly increased
      the expression of EC-SOD mRNA and protein in human monocytic U937 cells, but not
      those of CuZn-SOD or Mn-SOD. Induced EC-SOD by lysoPC had a high affinity for
      heparin, and may bind to the endothelial cell surface. Very recently, it has been
      reported that exogenous addition of EC-SOD or overexpression of EC-SOD prevented
      endothelial cell-mediated oxidative modification of LDL. Therefore, it is
      speculated that EC-SOD is induced by lysoPC-stimulated monocytes as a feedback
      mechanism in vascular homeostasis.

PMID- 12052469
TI  - Troglitazone inhibits growth and improves insulin signaling by suppression of
      angiotensin II action in vascular smooth muscle cells from spontaneously
      hypertensive rats.
AB  - Troglitazone, a thiazolizidinedione, has recently been reported to possess anti
      arteriosclerotic properties. To evaluate mechanisms underlying the anti
      arteriosclerotic effects of troglitazone, we examined the effect of troglitazone
      on growth, expression of growth factors, and insulin signaling in vascular smooth
      muscle cells (VSMC) from spontaneously hypertensive rats (SHR) which produce
      angiotensin II (Ang II) in a homogeneous culture. Troglitazone inhibited basal
      and serum-stimulated DNA synthesis and inhibited increases in the number of VSMC
      from SHR and normotensive Wistar-Kyoto (WKY) rats. Its inhibition was greater in
      VSMC from SHR. Troglitazone abolished DNA synthesis in response to Ang II in VSMC
      from both rat strains and markedly inhibited DNA synthesis in response to
      epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-AA in
      VSMC from SHR. Troglitazone did not alter the expression of transforming growth
      factor (TGF)-beta1, PDGF A-chain, or basic fibroblast growth factor (bFGF) mRNAs
      in VSMC from WKY rats, but it markedly decreased expression of these growth
      factor mRNAs in VSMC from SHR. Troglitazone markedly decreased basal and Ang II
      stimulated expression of extracellular signal-regulated kinase proteins in VSMC
      from both rat strains. Troglitazone abolished Ang II-induced suppression of
      phosphatidilinositol 3-kinase (PI3-kinase) activity, insulin receptor substrate-1
      (IRS-1) associated tyrosine phosphorylation, and IRS-1 associated p85 levels in
      VSMC from WKY rats. Basal PI3-kinase activity, tyrosine phosphorylation of IRS-1,
      and IRS-1 associated p85 levels were lower in VSMC from SHR than in cells from
      WKY rats. Troglitazone significantly increased PI3-kinase activity, IRS-1
      associated tyrosine phosphorylation, and IRS-1 associated p85 levels in VSMC from
      SHR. These results indicate that troglitazone produce its anti-arteriosclerotic
      effects through suppression of the action of growth-promoting factors including
      Ang II, and that troglitazone inhibits Ang II-induced suppression of insulin
      signaling in VSMC from SHR, suggesting that tissue Ang II may lead to insulin
      resistance and to arteriosclerosis in hypertension. Troglitazone may be useful in
      the treatment of insulin resistance as well as of hypertensive vascular diseases.

PMID- 12052470
TI  - A major gene influences variation in large HDL particles and their response to
      diet in baboons.
AB  - Some baboons accumulate appreciable amounts of large apoE-rich HDLs (HDL(1))
      which are similar to those reported in humans with several different
      dyslipoproteinemias. We estimated HDL(1) cholesterol concentrations by gradient
      gel electrophoresis of serum samples obtained from 634 pedigreed baboons fed with
      three diets differing in levels of fat and cholesterol. The HDL(1) trait was
      highly heritable on each diet (0.390< or =h(2)< or =0.528). Segregation analyses
      yielded significant evidence that a single major gene plus polygenes affected
      HDL(1) on a high-fat low-cholesterol diet. The major gene explained approximately
      56% of total trait variance and 90% of the additive genetic variance in HDL(1)
      levels in these baboons. Bivariate one-locus segregation analyses indicated that
      this major gene exerts significant pleiotropic effects on a number of traditional
      HDL traits on all three diets, including HDL size distributions, and
      concentrations of HDL-C, apoAI, and apoE. Linkage analyses showed that this major
      gene was not located in chromosomal regions that contain six candidate genes
      whose protein products are important to HDL metabolism (LCAT, CETP, APOA1, APOE,
      ABCA1, LIPC). Our results suggest this major gene in baboons plays a pivotal role
      in HDL metabolism, but is unlikely to code for any of the proteins previously
      implicated in studies of human HDL(1).

PMID- 12052471
TI  - Comparison of the effects of alpha-tocopherol, ubiquinone-10 and probucol at
      therapeutic doses on atherosclerosis in WHHL rabbits.
AB  - Oxidative modification of lipoproteins may trigger and maintain atherogenesis. We
      compared the effects of different antioxidants (alpha-tocopherol, probucol,
      ubiquinone-10) at doses similar to those used in humans in Watanabe Heritable
      Hyperlipidemic (WHHL) rabbits for 12 months. Aortic lesions were analyzed for
      their extent and cellular composition of lesions, mean thickness of fibrous caps
      and density of smooth muscle cells therein, content of antioxidants, non-oxidized
      and oxidized lipids. Compared to controls, probucol significantly lowered the
      extent and macrophage content of lesions and increased the existence and smooth
      muscle cell density of fibrous caps. alpha-Tocopherol supplementation increased
      the aortic content of vitamin E, but had no decreasing effect on either the
      accumulation of macrophage-specific antigen in the aorta or lesion size.
      Nevertheless, both probucol and alpha-tocopherol significantly decreased in vitro
      LDL oxidizability, measured under typically strong oxidative conditions.
      Ubiquinone-10 supplement increased lesion size and the fraction of lesions
      containing fibrous caps; however, LDL oxidizability remained unaffected by
      ubiquinone-10 treatment. None of the antioxidants tested lowered oxidized lipids
      within aortic tissue; however, long-term treatment with probucol provided the
      most effective anti-atherosclerotic effect, while alpha-tocopherol may be pro
      atherogenic and ubiquinone-10 exerts ambivalent effects. Our data suggest that
      (i) widely used oxidation measures, such as ex-vivo LDL oxidizability, do not
      reflect the degree of atherosclerosis; and (ii) long-term beneficial effects of
      relatively low doses of antioxidants may be outweighed by high levels of plasma
      cholesterol in WHHL rabbits.

PMID- 12052472
TI  - Does correction of the friedewald formula using lipoprotein(a) change our
      estimation of ischemic heart disease risk? The Quebec Cardiovascular Study.
AB  - BACKGROUND: LDL-cholesterol is usually calculated using the Friedewald formula.
      This calculation method does not take into account the presence of Lp(a), which
      is associated with LDL-cholesterol. Dahlen has suggested that the Friedewald
      formula should be modified to account for Lp(a) associated cholesterol. This
      study was undertaken to determine if correction of the Friedewald formula would
      result in a better evaluation of ischemic heart disease (IHD) risk. METHODS: 2222
      men free from IHD were prospectively followed for 5 years for the appearance of
      myocardial infarction, coronary insufficiency or coronary death. At the baseline
      evaluation all had a complete fasting lipid profile which included Lp(a)
      determinations. LDL-cholesterol levels were calculated from total cholesterol,
      total triglycerides and HDL-cholesterol using the Friedewald formula and also
      using the Dahlen modification of the Friedewald formula. RESULTS: During the
      follow-up there were 89 first IHD events. Both types of LDL-cholesterol
      calculations showed that the last tertile of the LDL-cholesterol distribution in
      comparison to the first tertile, doubles the relative risk (RR: 2.15; 95%
      confidence limits: 1.23-3.75) using the Friedewald formula (RR: 2.18; 95%
      confidence limits: 1.25-3.81) using the Dahlen modification. Lp(a) levels were
      not an independent predictor of IHD risk. CONCLUSION: Modification of the
      Friedewald formula to account for Lp(a) levels does not improve our evaluation of
      IHD risk.

PMID- 12052473
TI  - Metalloproteinase inhibitor attenuates neointima formation and constrictive
      remodeling after angioplasty in rats: augmentative effect of alpha(v)beta(3)
      receptor blockade.
AB  - Release of matrix metalloproteinases (MMP) from smooth muscle and foam cells
      following arterial injury facilitates cell migration, neointimal hyperplasia, and
      vessel wall remodeling. Inhibition of MMP activity using the hydroxamate, zinc
      chelating mimicers of collagen, Batimastat and Marimastat, has shown efficacy in
      reducing constrictive vascular remodeling 6 weeks after experimental angioplasty
      but not intimal hyperplasia. Vitronectin receptor (alpha(v)beta(3)) blockade
      interferes with binding of this integrin to MMP-2 and proteolyzed collagen,
      thereby reducing cell invasion. This study tests the effect of MMP inhibition,
      with and without vitronectin receptor (alpha(v)beta(3)) blockade, on neointima
      formation and arterial remodeling in a long-term model (up to 212 months) of
      balloon injury in vivo. Male Sabra rats were treated with Batimastat (BB-94,
      British Biotech Pharmaceuticals Ltd., 30 mg/kg, intraperitoneally) and/or the
      alpha(v)beta(3) receptor inhibiting RGD peptide, G-Pen-GRGDSPCA (GIBCO BRL, 0.1
      micromol), administered as a perivascular gel to the common carotid artery after
      balloon injury. Animals were sacrificed 3, 14, 25, and 75 days (n=21, 23, 22, and
      21) after injury. Animals treated with BB-94, peptide, or both had markedly
      increased absolute luminal area with markedly reduced luminal cross-sectional
      area narrowing by neointima and intima-to-media area ratio at all time points
      except for 3 days after balloon injury versus non-treated, ballooned animals.
      Combined treatment was significantly more effective than either one alone.
      Constrictive remodeling, most marked 212 months after balloon injury, was
      prevented at this time point in all treated animals. The pattern of reduction in
      luminal narrowing, neointimal formation, and constrictive remodeling across
      treatment groups correlated very significantly with the reduction in tissue MMP
      activity as determined by zymography at 3 days. Confirmation of the efficacy of
      this strategy in larger animals should be the next step toward testing the
      applicability of this novel approach to the interventional setting.

PMID- 12052474
TI  - Evaluation of the atrial natriuretic peptide gene in stroke.
AB  - The atrial natriuretic peptide (ANP) gene was, though inconclusive, implied to be
      etiologically related to stroke in rats and recently in humans. The present study
      tested the candidacy of ANP for stroke susceptibility by a combination of
      molecular genetic approaches. First, we undertook an association study using a
      reported ANP variant, G664A, in two case-control panels independently collected,
      which involved 970 Japanese subjects. Second, we compared the rat ANP gene
      sequences and neighboring marker alleles among stroke-prone SHR (SHRSP), normal
      SHR and WKY of an original inbred colony and we also compared brain ANP
      expression between SHRSP and normal SHR. In humans, we found no significant
      association between the 664A variant and stroke in the studied population. In
      rats, 21 polymorphic sites were identified by direct sequencing of 2170-bp ANP
      fragments, from which two distinct alleles, SHRSP- and WKY-types, were inferred.
      From a genealogical point of view, our data indicated that an SHRSP-type allele
      could not play a determinant role in stroke-proneness. Overall results did not
      support the disease relevance of ANP, disagreeing with previous reports. Thus,
      considerable caution should be taken when one attempts to transfer findings in
      the animal model to humans.

PMID- 12052475
TI  - Dose-dependent action of atorvastatin in type IIB hyperlipidemia: preferential
      and progressive reduction of atherogenic apoB-containing lipoprotein subclasses
      (VLDL-2, IDL, small dense LDL) and stimulation of cellular cholesterol efflux.
AB  - Type IIB hyperlipidemia is associated with premature vascular disease, an
      atherogenic lipoprotein phenotype characterised by elevated levels of
      triglyceride-rich VLDL and small dense LDL, together with subnormal levels of
      HDL. The dose-dependent and independent effects of a potent HMGCoA reductase
      inhibitor, Atorvastatin, at daily doses of 10 and 40 mg, were evaluated on
      triglyceride-rich lipoprotein subclasses (VLDL-1, VLDL-2 and IDL), on the major
      LDL subclasses (light LDL, LDL-1+LDL-2, D: 1.019-1.029 g/ml; intermediate LDL,
      LDL-3, D: 1.029-1.039 g/ml and small dense LDL, LDL-4+LDL+5, D: 1.039-1.063
      g/ml), on CETP-mediated cholesteryl ester transfer from HDL to apoB-containing
      lipoproteins, on phospholipid transfer protein activity and on plasma-mediated
      cellular cholesterol efflux in patients (n=10) displaying type IIB
      hyperlipidemia. Plasma concentrations of triglyceride-rich lipoprotein subclasses
      (TRL: VLDL-1, Sf 60-400; VLDL-2, Sf 20-60 and IDL, Sf 12-20) and of LDL (D: 1.019
      1.063 g/ml) were markedly diminished after 6 weeks of statin treatment at 10 mg
      per day (-31 and -36%, respectively; P<0.002) and by 42 and 51%, respectively at
      the 40 mg per day dose. Increasing doses of atorvastatin progressively normalised
      both the quantitative and qualitative features of the LDL subclass profile, in
      which dense LDL predominated at baseline. Indeed, dense LDL levels were reduced
      by up to 57% at the 40-mg dose, leading to a shift in the peak of the density
      profile towards larger, buoyant LDL particles typical of normolipidemic subjects.
      In addition, marked reduction in numbers of apoB100-containing particle acceptors
      led to a 30% decrease (P<0.02) in CETP-mediated CE transfer from HDL. Finally, a
      significant dose-dependent statin-mediated elevation (+15% at 10 mg; P=0.0003 and
      +35% at 40 mg; P<0.0001 compared to baseline) in the capacity of plasma from type
      IIB subjects to mediate free cholesterol efflux from Fu5AH hepatoma cells was
      observed. Moreover, atorvastatin (40 mg per day) significantly increased plasma
      apoAI levels (+24%; P<0.05), thereby suggesting that this statin enhances
      production of apoAI and with it, formation of nascent pre-beta HDL particles.
      Plasma PLTP activity was not affected by either dose of atorvastatin. We conclude
      that increasing the dose of atorvastatin leads to dose-dependent, preferential
      and progressive reduction in particle numbers of atherogenic VLDL-2, IDL and
      dense LDL, and concomitantly, to enhanced cellular cholesterol efflux in type IIB
      dyslipidemia, thereby diminishing the atherosclerotic burden in subjects
      characterised by high cardiovascular risk.

PMID- 12052476
TI  - Acute phase reactants in patients with abdominal aortic aneurysm.
AB  - BACKGROUND: There is increasing evidence that an inflammatory process is present
      in abdominal aortic aneurysms (AAAs) to varying degrees. The aim of this study
      was to compare acute phase reactants in patients with asymptomatic AAA,
      symptomatic AAA without rupture and ruptured AAA. METHOD: Two hundred and twenty
      five consecutive patients treated because of AAA were included in this case
      control study. Polynomial logistic regression analysis was applied to compare
      admission C-reactive protein (CRP) and white blood count (WBC) measured in 111
      asymptomatic outpatients, 52 symptomatic patients without rupture and 62 patients
      with rupture of the aneurysm. We adjusted for the potentially confounding effect
      of age, sex, haemoglobin levels and aneurysm diameter. RESULTS: Patients with
      symptomatic AAA and patients with ruptured AAA had significantly elevated CRP
      (p=0.002) and WBC (p<0.0001) levels compared to asymptomatic patients. There was
      no statistically significant difference in CRP and WBC between patients with
      symptomatic AAA and ruptured AAA. Median CRP values of asymptomatic, symptomatic
      and ruptured AAA were <0.5 (interquartile range (IQR) <0.5-0.85), 1.1(IQR <0.5
      4.0) and 2.4 mg/dl (IQR 0.65-8.6), respectively, and median WBC values were 6.5
      (IQR 5.5-8.0), 8.7 (IQR 6.8-11.2) and 13.2 (IQR 10.5-17.0), respectively.
      CONCLUSION: A significant elevation of CRP and WBC could be found in patients who
      presented with symptoms or rupture of an AAA. These indicators of inflammation
      were not observed in asymptomatic patients with AAA.

PMID- 12052478
TI  - Changes in serum lipid levels during a 10 year period in a large Japanese
      population. A cross-sectional and longitudinal study.
AB  - To determine the recent secular trends in serum lipid levels and characterize
      their influence on the aging process, we examined a large cohort of Japanese
      cross-sectionally and longitudinally. The participants included 80331 Japanese
      men and women 20-79 years of age, who had received annual health examinations
      from 1989 to 1998. In cross-sectional analysis, an increase in total and LDL
      cholesterol as well as triglyceride levels was observed in the population during
      the period of 1989-1998. The longitudinal changes showed that total and LDL
      cholesterol increased with age in men between the birth cohorts of the 1920s and
      1960s. In women, these cholesterol levels increased in the 1930s and younger
      cohorts. HDL cholesterol decreased in men of all birth cohorts. However, HDL
      cholesterol increased in women of the 1940s and younger cohorts. Triglyceride
      levels increased in men of the 1940s and younger cohorts but decreased in the
      1930s and older. Triglyceride levels increased in women of the 1930s and younger.
      Longitudinal analysis also suggested a birth cohort effect except for the
      triglyceride level for women. These results suggest that Japanese serum lipid
      levels continue to increase and that there exist birth cohort effects regarding
      serum lipid levels in the Japanese population.

PMID- 12052477
TI  - Lowering of dietary advanced glycation endproducts (AGE) reduces neointimal
      formation after arterial injury in genetically hypercholesterolemic mice.
AB  - Restenosis remains a major cause of morbidity and mortality after coronary
      angioplasty. Injury-induced inflammation, thrombosis, smooth muscle cell (SMC)
      proliferation, and neointimal formation contribute to restenosis. These events
      are linked to circulating glucose-derived advanced gycation endproducts (AGE),
      known to promote cell proliferation, lipid glycoxidation and oxidant stress. This
      study evaluates the association between dietary AGE content and neointimal
      formation after arterial injury in genetically hypercholesterolemic mice. Male,
      12-week-old, apolipoprotein E-deficient (apoE(-/-)) mice were randomly assigned
      to receive either a high AGE diet (HAD; AGE=15000 U/mg), or a similar diet with
      ten-fold lower AGE (LAD; AGE=1500 U/mg). These mice underwent femoral artery
      injury 1 week later, and were maintained on their diets for an additional 4
      weeks. At 4 weeks after injury, significant decrease in neointimal formation was
      noted in LAD-fed mice. Neointimal area, intima/media ratio, and stenotic luminal
      area (LA) were less pronounced in the LAD group than the HAD group (P<0.05).
      These quantitative differences were associated with a marked reduction (
      approximately 56%) of macrophages in the neointimal lesions, as well as an
      obvious reduction of SMC content of LAD-fed mice. The reduction of neointimal
      formation in the LAD mice correlated with a approximately 40% decrease in
      circulating AGE levels (P<0.0005). Immunohistochemistry also showed a reduced (
      approximately 1.5-fold) deposition of AGE in the endothelia, SMC, and macrophages
      in neointimal lesions of LAD-fed mice. These results represent the first evidence
      in vivo for a causal relationship between dietary AGE and the vessel wall
      response to acute injury, suggesting a significant potential for dietary AGE
      restriction in the prevention of restenosis after angioplasty.

PMID- 12052479
TI  - Correction of long-term diet-induced hypertension and nitrotyrosine accumulation
      by diet modification.
AB  - Several recent studies have demonstrated that various forms of hypertension are
      associated with enhanced reactive oxygen species (ROS) activity. We have recently
      shown that long-term consumption of a diet similar to that ingested in
      westernized societies, containing high saturated fat and refined carbohydrate,
      induces oxidative stress and hypertension in normal rats. We hypothesized that
      diet modification may reverse diet-induced hypertension via (among other
      mechanisms) decreased ROS activity and improved nitric oxide (NO) availability.
      To test this hypothesis, female Fischer rats were placed on either a high-fat
      (primarily saturated), refined carbohydrate (sucrose) diet (HFS) or low-fat,
      complex-carbohydrate diet (LFCC) starting at 2 months of age. After 2 years when
      hypertension was well established, a group of HFS rats was converted to the LFCC
      diet (HFS/LFCC group) for a period of 2 months. Plasma malondialdehyde, a marker
      of lipid peroxidation by ROS, was elevated in the HFS group. Hypertension was
      present in the HFS group at 2 years as was a significant accumulation, in various
      tissues, of nitrotyrosine, which is the footprint of NO inactivation by ROS.
      Conversion from the HFS to the LFCC diet for 2 months led to normalization of
      blood pressure and reduced nitrotyrosine accumulation in the absence of caloric
      restriction. These results demonstrate that oxidative stress and hypertension
      induced by long-term consumption of an HFS diet are reversible with
      implementation of a low-fat, unrefined carbohydrate diet. The effects of the HFS
      diet and subsequent conversion to the LFCC diet on blood pressure appear to be,
      in part, mediated by changes in NO availability.

PMID- 12052480
TI  - Genetic variation in the apolipoprotein D gene among African blacks and its
      significance in lipid metabolism.
AB  - Apolipoprotein D (APOD, gene; apoD, protein) is a plasma high-density lipoprotein
      (HDL)-associated glycoprotein, with a putative role in the cholesterol (CHOL)
      transport pathway. An apoD protein polymorphism has been previously reported by
      us. The cathodically shifted pattern seen on isoelectric focusing gels,
      controlled by the APOD*2 allele, was found to be unique to populations of African
      ancestry. To characterize the molecular basis of the protein polymorphism and to
      identify new mutations, we used a combination of SSCP, DHPLC and DNA sequencing
      techniques to screen the entire coding region of the APOD gene. We identified
      three distinct missense mutations, including Phe36Val, Tyr108Cys, and Thr158Lys
      with frequencies ranging from 2.1 to 2.8% in 722 African blacks from Nigeria. In
      addition, a common 8 bp deletion polymorphism was observed in intron 1 with a
      carrier frequency of 30.1%. The missense mutation, Thr158Lys correlated with the
      APOD*2 allele of the protein polymorphism. None of the 454 Caucasians screened
      for these polymorphisms showed any variation. We also determined the effect of
      these polymorphisms on plasma lipid levels in the African black population by
      generalized linear model (GLM). The Val36 allele was associated with
      significantly decreased HDL3-C (P=0.027) and apoA-I (P=0.030) levels among
      females. The Lys158 allele was associated with significantly increased Lp(a)
      (P=0.018) and triglyceride (P=0.017) levels, among females and males,
      respectively. In addition, males heterozygous for both intron 1 and codon 108
      polymorphisms showed significantly increased HDL-C (P=0.011), HDL3-C (P=0.041),
      HDL2-C (P=0.009), apoA-I (P=0.005) and decreased LDL-C (P=0.025) levels. The
      results of our study show that the APOD gene harbors several polymorphisms, which
      are unique to African populations. Further study of these polymorphisms may help
      to characterize the role of apoD in lipid metabolism, and in cardiovascular
      disease among African populations.

PMID- 12052481
TI  - The effect of the phytoestrogen genistein on plasma nitric oxide concentrations,
      endothelin-1 levels and endothelium dependent vasodilation in postmenopausal
      women.
AB  - The phytoestrogen genistein improves endothelial dysfunction in ovariectomized
      rats through a nitric oxide-dependent mechanism. We investigated whether
      genistein alters the balance between the nitric oxide products and endothelin-1
      and influences endothelium-dependent vasodilation in postmenopausal women. Sixty
      healthy postmenopausal women were enrolled in the study. A double-blind, placebo
      controlled, randomized design was employed. After a 4-week stabilization on a
      standard fat-reduced diet, participants to the study were randomly assigned to
      receive either genistein (n=30; 54 mg/day) or placebo (n=30). Flow-mediated,
      endothelium-dependent vasodilation of the brachial artery, plasma nitric oxide
      breakdown products and endothelin-1 levels were measured at baseline and after 6
      months of genistein therapy. The mean baseline level of nitrites/nitrates was
      22+/-10 micromol/l and increased to 41+/-10 micromol/ml after 6 months of
      treatment. The mean baseline plasma endothelin-1 level was 14+/-4 pg/ml and
      decreased to 7+/-1 pg/ml following 6 months of treatment with genistein. The mean
      baseline ratio of nitric oxide to endothelin also significantly increased at the
      end of treatment. Flow-mediated, endothelium-dependent vasodilation of the
      brachial artery was 3.9+/-0.8 mm at baseline and increased to 4.4+/-0.7 mm after
      6 months of treatment. Placebo-treated women showed no changes in plasma
      nitrites/nitrates, endothelin-1 levels and flow-mediated vasodilation. Genistein
      therapy improves flow-mediated endothelium dependent vasodilation in healthy
      postmenopausal women. This improvement may be mediated by a direct effect of
      genistein on the vascular function and could be the result of an increased ratio
      of nitric oxide to endothelin.

PMID- 12052482
TI  - Pilot study of coronary atherosclerotic risk and plaque burden in HIV patients:
      'a call for cardiovascular prevention'.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically
      improved the life expectancy of patients with human immunodeficiency virus (HIV)
      prompting increasing concerns related to chronic management. Suggestions of
      greater cardiovascular risk, partially related to recently proposed HAART-induced
      dyslipidemia and glucose intolerance, amplify these concerns. At this time,
      further corroboration of the emerging evidence for increased coronary risk, as
      well as complimentary estimates of coronary artery atherosclerotic burden, would
      be valuable to practicing physicians. METHODS: Seventeen HIV patients on HAART
      (all from the same HIV clinic population) without coronary artery disease (CAD)
      were referred to Preventive Cardiology for treatment of dyslipidemia ('referred
      group'). Upon entry, they underwent computed tomography (CT) of the coronary
      arteries. Subsequently, the referred group was matched (1:4) for age, gender and
      traditional risk to non-HIV non-CAD subjects (matched group, n=68) from the
      University of Illinois CT database. A serial review of 90 subjects from the
      original HIV population was sampled to determine general cardiovascular risk.
      RESULTS: Thirteen (76%) of the 17 referred patients revealed the presence of
      coronary calcium compared with 63% in the matched HIV seronegative controls
      (P=0.18). Log-transformed median calcium score was 2.93+/-2.3 in the referred
      group versus 1.97+/-2.5 in the matched group (P=0.09). Fifty one percent of the
      overall population smoked cigarettes, 11% were diabetic (30% diagnosed pre-HAART
      and 70% post-HAART) and 30% were hypertensive (33% diagnosed pre-HAART and 67%
      post-HAART). CONCLUSIONS: In a particularly dyslipidemic subgroup of HIV subjects
      without known CAD we found evidence for atherosclerosis in three-quarters based
      on coronary calcium. Further, in this population of HIV patients on HAART, we
      found an enhanced prevalence of traditional cardiovascular risk. This pilot study
      encourages the development of preventive strategies in this population.

PMID- 12052483
TI  - Reduced structural and functional skin capillaries in familial combined
      hyperlipidemia affected men, associated with increased remnant-like lipoprotein
      cholesterol levels.
AB  - We determined whether abnormalities in the number of basal (BC) and post
      occlusive (POC) capillaries are present in familial combined hyperlipidemia
      (FCHL), and investigated the possible relationship of BC and POC with lipids,
      remnant-like lipoprotein particles (RLP-C), blood pressure, and insulin
      resistance. Fifty age-matched subjects, 23 (12 men) hyperlipidemic, normotensive
      FCHL subjects and 27 (14 men) healthy controls participated in this study.
      Capillary density was measured just above the finger nailfold, before and after 4
      min of arterial occlusion. The number of BC and POC were significantly lower in
      FCHL men compared with healthy men, 113.7+/-15.1 versus 132.0+/-18.0 (P=0.02) and
      123+/-19.1 versus 142.3+/-18.3 (P=0.03), respectively. No differences were found
      between FCHL women and control women. In univariate analyses in FCHL men, BC was
      inversely correlated with total cholesterol (r=-0.63; P=0.05). POC tended to be
      inversely correlated with total cholesterol (r=-0.62; P=0.056). No univariate
      correlations (P>0.3) were observed between BC or POC and blood pressure or
      insulin resistance. Multivariate analyses revealed that logRLP-C was the only
      significant independent contributor to BC and POC. This is the first description
      of a reduction in skin capillaries in FCHL men, which was associated with
      increased atherogenic lipoprotein levels. Loss of capillary surface may be
      important in the pathophysiology or can result from adaptation to the
      hyperlipidemia in FCHL.

PMID- 12052485
TI  - Increased fibrinogen, von Willebrand factor and tissue plasminogen activator
      levels in insulin resistant South Asian patients with ischaemic stroke.
AB  - The aim of this study was to determine differences in atherothrombotic risk
      factors in South Asian subjects with a history of ischaemic stroke and South
      Asian subjects free from personal and family history of clinically detectable
      stroke. Eighty South Asian patients with ischaemic stroke (confirmed on cranial
      computerised scan) and 80 South Asian controls with similar age and gender
      distributions were recruited at random. The frequency of hypertension
      (P=<0.0001), myocardial infarction (P=0.003) and diabetes mellitus (<0.0001) were
      significantly higher in stroke patients. Stroke patients had lower high-density
      lipoprotein cholesterol (0.95 vs. 1.1 mmol/l, P=<0.0001), higher plasma glucose
      (8.1 vs. 6.6 mmol/l, P=0.01) and trendwise higher HBA(1C) (6.4 vs. 6.0%, P=0.09).
      There was no difference in insulin levels but insulin resistance was
      significantly higher in stroke patients (3.75 vs. 2.66, P=0.01). Stroke patients
      showed elevated levels of fibrinogen (3.78 vs. 3.41 mg/dl, P=0.02), von
      Willebrand factor (1.78 vs. 1.50 IU/ml, P=0.006) and tissue plasminogen activator
      (12.8 vs. 11.3 ng/ml, P=0.04), but the differences did not persist after
      adjustment for glucose, triglycerides, HDL, WHR, and BMI. Higher levels of
      fibrinogen, von Willebrand factor and t-PA in South Asian stroke patients
      disappeared after adjustment for features of insulin resistance syndrome but
      persisted after adjustment for presence of diabetes, confirming that these
      changes are essentially dependant on features of insulin resistance syndrome. A
      prospective study would be required to elucidate the role of thrombotic risk
      factors in South Asians with ischaemic stroke.

PMID- 12052484
TI  - Activated factor XII levels and factor XII 46C>T genotype in relation to coronary
      artery calcification in patients with type 1 diabetes and healthy subjects.
AB  - The relationship of activated factor XII (FXIIa) and FXII 46C>T genotype to
      coronary atherosclerosis and endothelial function was examined in 192 randomly
      sampled subjects from the general population and 190 type 1 diabetic subjects
      (mean age 38+/-4 years). Coronary artery calcification (CAC) was measured using
      Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function,
      and FXIIa were measured by ELISA. Endothelial nitric oxide production was
      quantified as the forearm blood flow response to intra-brachial infusion of
      bradykinin and N(G) monomethyl-L-arginine (L-NMMA). A higher FXIIa was
      independently associated with higher triglycerides (P<0.001), BMI (P=0.001),
      alcohol consumption (P=0.003) and vWF (P<0.001) in non-diabetic subjects and with
      insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P<0.001) in
      diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non
      diabetic subjects (1.92 ng/ml, P<0.001). Higher FXIIa was associated with lower
      response to bradykinin (P=0.048) and to L-NMMA (P=0.029). FXIIa was positively
      associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but
      not independently of other risk factors (odds ratio=1.1 on adjustment). 46C>T
      genotype explained 18% of the variance in FXIIa (P<0.001) but was not associated
      with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control
      but also reflects plasma triglycerides and endothelial activation or dysfunction.
      FXIIa appears unlikely to be directly atherogenic but may be a useful marker of
      coronary atherosclerosis because of its association with these other factors.
      Type 1 diabetes is associated with lower levels of FXIIa despite a greater
      prevalence of atherosclerosis.

PMID- 12052486
TI  - Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study.
AB  - The association of an elevated level of lipoprotein (a) (Lp(a)) with the
      development of coronary heart disease (CHD) remains controversial. Lp(a) was
      investigated as a CHD risk factor in the PRIME Study, a prospective cohort study
      which included 9133 French and Northern Irish men aged 50-59 at entry, without a
      history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years,
      288 subjects experienced at least one CHD event (myocardial infarction (MI),
      coronary death, angina pectoris). Lp(a) was measured by immunoassay in all
      subjects on fresh plasma obtained at entry. Traditional cardiovascular risk
      factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol,
      triglycerides, the presence of diabetes, hypertension or smoking were determined.
      Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk
      factor after controlling for the other risk factors. In addition, its possible
      interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared
      a significant risk factor (P<0.0006) in the whole cohort without between
      population interaction, even if the association was not statistically significant
      in the Belfast sample. The relative risk (RR) of CHD events in subjects with
      Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest
      quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a)
      level was a risk for MI, coronary death and angina pectoris. A significant
      interaction term between Lp(a) and LDL-cholesterol levels, however, was found.
      The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison
      with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men
      with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06
      2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the
      risk for MI and angina pectoris, especially in men with a high LDL-cholesterol
      level. This study which analyzed Lp(a) level using a measurement independent of
      apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a
      predictor of CHD.

PMID- 12052488
TI  - Genetic characterization of Swedish patients with familial hypercholesterolemia:
      a heterogeneous pattern of mutations in the LDL receptor gene.
AB  - Familial hypercholesterolemia (FH) is an autosomal codominant disease, caused by
      mutations in the LDL receptor gene. To characterize the distribution of genetic
      aberrations in Swedish FH-patients fulfilling the clinical criteria of FH, we
      have investigated 150 unrelated Swedish patients for mutations in the LDL
      receptor gene and for the most common mutation causing familial ligand defective
      apo B-100 (FDB). Of the patients, 77 were recruited from Huddinge University
      Hospital in Stockholm and 73 from Sahlgren's University Hospital in Goteborg.
      Screening was carried out using SSCP and Southern blotting techniques, combined
      with DNA sequence analysis. In total, mutations regarded as cause for disease
      were identified in 55 patients (37%), representing 32 different types of
      mutations. In the LDL receptor gene we detected four nonsense mutations, 13
      missense mutations, seven splice junction mutations, and four major
      rearrangements. In addition, two small deletions were identified and one base
      exchange in the promoter region. The most common mutation (apo B3500) causing FDB
      was found in three patients. The most frequent mutation was FH-Helsinki,
      reflecting the admixture of Finnish immigrants. We further identified 15 point
      mutations which were not considered to affect the function of the gene, and thus
      were regarded as polymorphic changes. This multitude of mutations reflects a
      heterogeneous genetic background in our series of Swedish FH-patients and differs
      from the situation in the other Scandinavian countries. Future studies should aim
      at characterizing the importance of other genes for the development of the FH
      phenotype.

PMID- 12052487
TI  - Protective effect of dietary monounsaturated fat on arteriosclerosis: beyond
      cholesterol.
AB  - The consumption of diets enriched in monounsaturated fat has been related to a
      lower rate of coronary heart disease. It is well known that this dietary model
      decreases LDL-cholesterol plasma levels when replacing a saturated fat enriched
      diet. For this reason, a high monounsaturated fat diet is now being advocated to
      prevent cardiovascular disease, especially in Mediterranean countries. However,
      some expert panels-the Joint Task Force of European and other Societies on
      Coronary Prevention and the International Task Force for Prevention of Coronary
      Heart Disease-recommend replacing dietary saturated fat by complex carbohydrates,
      limiting the intake of total fat to <30% of the energy and monounsaturated fat to
      no more than 10-15% of total calories, reaching a similar effect on LDL
      cholesterol plasma levels to a high monounsaturated fat diet. The most
      appropriate nutritional model to prevent arteriosclerosis should be supported by
      research into other biological effects of both diets. Therefore, it is
      interesting to review the non-lipid effect of monounsaturated fat, starting with
      its influence on other cardiovascular risk factors, such as carbohydrate
      metabolism and blood pressure. Moreover, substantial evidence of the effect of
      dietary monounsaturated fat on a wide range of healthy benefits beyond
      cholesterol, which have been investigated in recent years, such as lipoprotein
      oxidation, coagulation, fibrinolysis and endothelium, will be discussed.
      Furthermore, many observational epidemiological studies suggest that a high
      intake of monounsaturated fat is associated with reduced coronary risk and this
      will be analyzed in accordance with the clinical evidence to discuss the best
      dietary model to prevent coronary artery disease.

PMID- 12052489
TI  - Multiple Methods for Reduction of Lipoprotein(a).

PMID- 12052490
TI  - Quantitative assessment of human erythrocyte membrane solubilization by Triton X
      100.

PMID- 12052491
TI  - Conformational transition of DNA induced by cationic lipid vesicle in acidic
      solution: spectroscopy investigation.
AB  - The conformational transition of DNA induced by the interaction between DNA and a
      cationic lipid vesicle, didodecyldimethylammonium bromide (DDAB), had been
      investigated by circular dichroism (CD) and UV spectroscopy methods. We used
      singular value decomposition least squares method (SVDLS) to analyze the
      experimental CD spectra. Although pH value influenced the conformation of DNA in
      solution, the results showed that upon binding to double helical DNA, positively
      charged liposomes induced a conformational transition of DNA molecules from the
      native B-form to more compact conformations. At the same time, no obvious
      conformational changes occurred at single-strand DNA (ssDNA). While the cationic
      lipid vesicles and double-strand DNA (dsDNA) were mixed at a high molar ratio of
      DDAB vesicles to dsDNA, the conformation of dsDNA transformed from the B-form to
      the C-form resulting in an increase in duplex stability (DeltaT(m)=8+/-0.4
      degrees C). An increasing in T(m) was also observed while the cationic lipid
      vesicles interacted with ssDNA.

PMID- 12052492
TI  - Kinetics of iron release from pig spleen ferritin with bare platinum electrode
      reduction.
AB  - Several anaerobic electrochemical cells were employed to study the kinetics of
      iron release from pig spleen ferritin (PSF) at a bare platinum electrode.
      Controlled potential microcoulometry (CPM) is the principal technology used to
      investigate the kinetics in the absence of a mediator. A kinetic study of iron
      release by microcoulometry has revealed that ferritin undergoes direct electron
      transfer at the electrode in the absence of a mediator, indicating that ferritin
      is an electroactive protein. Several experiments failed to show that alpha'alpha
      bipyridyl has the capacity to reduce hydrolyzed Fe(3+) within the ferritin core
      after it has been reduced by the electrode at -600 mV vs. NHE in the absence of
      mediator. PSF is known to bind heme to generate a hemeoprotein, named pig spleen
      hemeoferritin (PSF(ho)). The rate of iron release is accelerated by the heme
      binding to PSF(ho) without the need for small mediators. Under similar
      conditions, two kinetic processes for iron release from PSF and bacterial
      ferritin of Azoaobacter vinelandii (AvBF) were studied and both fit a zero-order
      law. In addition, the rate of iron release in PSF can be accelerated two-fold by
      a specific reduction system consisting of ascorbic acid (AA) and the bare
      platinum electrode at -600 mV. However, this kinetic process does not follow zero
      , half-, first, or second-order rate laws. A model is proposed to explain a
      mechanism of direct electron transfer between ferritin and the electrode is
      derived to describe the kinetics of iron release.

PMID- 12052493
TI  - Fluorescence pattern photobleaching recovery for samples with multi-component
      diffusion.
AB  - The translational mobility of proteins and lipids in phospholipid bilayers is
      often not well described as ideal self diffusion. One of the best methods for
      characterizing such non-ideal diffusion is to use fluorescence pattern
      photobleaching recovery. In this method, the spatial gradient of the monitoring
      and bleaching intensity is created by using epi-fluorescence and an expanded
      Gaussian-shaped laser beam which passes though a Ronchi ruling placed at the back
      image plane of a microscope. A difficulty arises when the fluorescence recovery
      from the exchange of slowly diffusing molecules between illuminated and non
      illuminated stripes temporally overlaps with the recovery from the exchange of
      more rapidly diffusing molecules through the gradient produced by the broad
      Gaussian shape of the illumination. In the work presented here, a general theory
      is developed that describes the shape of the resulting fluorescence recovery
      curve for these typical experimental conditions. Approximate expressions amenable
      to non-linear curve fitting are also given. The new theoretical formalism has
      been demonstrated on data for the translational mobility of a fluorescent lipid
      probe in phospholipid bilayers deposited on planar-fused silica substrates.

PMID- 12052494
TI  - Solubilization of human erythrocyte membranes by non-ionic surfactants of the
      polyoxyethylene alkyl ethers series.
AB  - In the present study, we investigated the interaction of the non-ionic
      surfactants polyoxyethylene alkyl ethers (C(n)E(m)) with erythrocyte membranes.
      For this purpose we have performed hemolytic assays under isosmotic conditions
      with five surfactants in the 8 polyoxyethylene ether series. By applying to the
      hemolytic curves a quantitative treatment developed for the study of surface
      active compounds on biomembranes, we could calculate the surfactant/lipid molar
      ratios for the onset of hemolysis (R(e)(sat)) and for complete hemolysis
      (R(e)(sol)). This approach also allowed the calculation of the binding constants
      for each surfactant to the erythrocyte membrane. Results in the C(n)E(m) series
      were compared to those obtained for Triton X-100, a well-known non-ionic
      surfactant with values of cmc and HLB in the range of the alkyl ethers studied.
      Inside the series the lytic effect increased with the more hydrophobic homologues
      (C(10)E(8)<C(12)E(8)<C(14)E(8)<C(16)E(8)<C(18)E(8)), with Re values between 3:1
      and 0.03:1. The effect of C(10)E(8) and C(12)E(8) was found to be in the range of
      that caused by Triton X-100, proving that C(n)E(m) surfactants are strongly
      hemolytic.

PMID- 12052495
TI  - Interaction of the IP(3)-Ca(2+) and the FGF-MAPK signaling pathways in the
      Xenopus laevis embryo: a qualitative approach to the mesodermal induction
      problem.
AB  - In this work we propose that the animal-vegetal gradient spatial distribution of
      the IP(3) receptors observed in the Xenopus embryo can effect a uniform FGF
      inducting input signal, allowing for different modes of transcription of the Xbra
      gene, producing the differentiation of the cells of the marginal zone. We analyze
      this hypothesis with a model for the interaction of the calcium signaling system
      with the MAPK cascade during the FGF mesodermal induction process, consisting of
      five non-linear coupled differential equations. A numerical treatment of a one-
      and two-cell system shows that the calcium flux between cells enhances the Raf
      activity levels, leading to oscillatory behavior. This qualitative result may be
      of consequence for the expression of the ventralizing characteristics of the FGF
      inducting signal.

PMID- 12052496
TI  - Heat capacity of folding of proteins corrected for disulfide cross-links.
AB  - The heat capacities (DeltaC(p,f)) for the temperature-induced folding of
      proteins: barnase, lysozyme T4, papain, trypsin, ribonuclease T1, chymotrypsin,
      lysozyme and ribonuclease A have been calculated from the change in solvent
      accessible surface area between the native state and extended polypeptide chain.
      To visualize the effect of disulfide cross-links on molar heat capacity, loops of
      varying number of alanine residues and extended alanine chains with terminal
      cystein are modeled. The difference in DeltaC(p) values between the extended
      state and the loop conformation of proteins is linearly related to the number of
      residues in the loop. Corrections to the heat capacity of folding (DeltaC(p,f))
      are applied for proteins with cross-links based on this observation. There is
      good correlation between corrected values of DeltaC(p,f) and experimental values.

PMID- 12052497
TI  - Metal ion complexation and folding of linear peptides.
AB  - A Linear peptide, GASYQDLG was synthesised and used as a model to evaluate the
      effects of nickel additions to increase the conformational stability. The NMR
      data obtained for the peptide and its histidyl derivative (H)(3)GASYQDLG(H)(3)
      suggest that in solution folded structures are present only for the H-tagged
      peptide-Ni(II) ion system. These results suggest that metal ions and additions of
      a double histidine tags of suitable length can be used as efficient tools to
      reduce peptide flexibility without other internal modifications. Synthesis of H
      tagged analogs could offer a promising strategy for large-scale preparation of
      diagnostic tools and, in general, whenever more rigid molecular structures should
      be advisable.

PMID- 12052498
TI  - Low dose, low-LET ionizing radiation-induced radioadaptation and associated early
      responses in unirradiated cells.
AB  - Numerous investigators have reported that irradiation of cells with a low dose of
      ionizing radiation (IR) can induce a condition of enhanced radioresistance, i.e.
      a radioadaptive response. In this report, we investigated the hypothesis that a
      radioadaptive bystander effect may be induced in unirradiated cells by a
      transmissible factor(s) present in the supernatants of cells exposed to low dose
      gamma-rays. Normal human lung fibroblasts (HFL-1) were irradiated with a 1 cGy
      dose of gamma-rays and their supernatants were transferred to unirradiated HFL-1
      as a bystander cell model. Compared with the directly irradiated cells, such
      treatment resulted in increased clonogenic survival following subsequent gamma
      irradiation with 2 and 4 Gy. This radioadaptive bystander effect was found to be
      preceded by early decreases in cellular levels of TP53 protein, increase in
      intracellular ROS, and increase in the redox and DNA repair protein AP
      endonuclease (APE). The demonstration that radioadaptation can occur in
      unirradiated cells via a fluid-phase, transferable factor(s) adds to the
      complexity of the current understanding of mechanisms by which radioadaptive
      responses can be induced by low dose, low-LET IR.

PMID- 12052499
TI  - Influence of mus201 and mus308 mutations of Drosophila melanogaster on the
      genotoxicity of model chemicals in somatic cells in vivo measured with the comet
      assay.
AB  - To check the possibilities of the recently developed comet assay, to be used in
      mechanistic studies in Drosophila melanogaster, neuroblast cells of third instar
      larvae are used to analyse in vivo, the effect of two repair deficient mutations:
      mus201, deficient on nucleotide excision repair, and mus308, deficient in a
      mechanism of damage bypass, on the genotoxicity of methyl methanesulphonate
      (MMS), ethyl methanesulphonate (EMS) and N-ethyl-N-nitrosourea (ENU). The
      obtained results reveal: (1) MMS-induced breaks are most probably consequence of
      N-alkylation damage mediated abasic (AP) site breakage; (2) MMS and at least part
      of the EMS induced damage leading to DNA strand breaks are efficiently repaired
      by the nucleotide excision repair mechanism; (3) ENU and part of EMS induced
      damage need a functional Mus308 protein to be processed, otherwise they can lead
      to DNA strand breaks. In addition, the results of this work confirm the validity
      of neuroblast cells to conduct the comet assay, and the usefulness of this assay
      in in vivo mechanistic studies related to DNA repair in D. melanogaster.

PMID- 12052500
TI  - Putative identification of functional interactions between DNA intercalating
      agents and topoisomerase II using the V79 in vitro micronucleus assay.
AB  - Clastogenicity is frequently observed following treatment of mammalian cells with
      new chemical entities. This clastogenicity, unless proven otherwise, is assumed
      to result from the imperfect repair of DNA lesions produced from covalent
      chemical/DNA interaction. However, clastogenicity can also arise via other
      mechanisms such as non-covalent chemical intercalation into DNA resulting in
      poisoning of cellular DNA topoisomerase II (topo II) and stabilization of DNA
      double strand breaks. We have recently reported modifications to the V79 in vitro
      micronucleus assay which allow an indirect evaluation of both the intercalative
      and topoisomerase-interactive activities of chemical agents. In the present
      studies we have used these modified assays to further assess the validity of this
      approach in an evaluation of a number of intercalating and non-intercalating
      polycyclic compounds. It is shown that intercalating agents may be catalytic topo
      II inhibitors (e.g. chloroquine (CHL), tacrine (TAC), 9-aminoacridine (9AA),
      ethidium bromide (EB)) or topo II poisons (e.g. proflavine (PROF), auramine O
      (AUR) and curcumin (CURC)). Still other intercalators are shown to lack
      detectable topo II-interactions, (e.g. imipramine (IMP), quinacrine (QUIN), 2
      aminoanthracene (AA), iminostilbene (IMN) and promethazine (PHE)). It is
      concluded that (1) the clastogenicity of three agents, PROF (a typical DNA
      intercalating agent), and AUR and CURC (both structurally atypical intercalating
      agents, with unknown clastogenic mechanisms), may be due to topo II poisoning;
      (2) other intercalating agents may either act as catalytic topo II inhibitors or
      exhibit no functional topo II interaction; (3) The use of these cell-based
      approaches may provide a logical first step in determining if unexpected
      clastogenicity associated with test article exposure is due to a topo II
      interaction.

PMID- 12052501
TI  - A hMLH1 genomic mutation and associated novel mRNA defects in a hereditary non
      polyposis colorectal cancer family.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC), or Lynch syndrome I, is
      responsible for as high as 10% of all colorectal cancers (CRCs) newly diagnosed
      in any given year. This disorder has an autosomal dominant inheritance pattern
      and is almost fully penetrant (>85%). It occurs when there is a mutation in any
      one of six mismatch repair genes: hMLH1, hMSH2, hPMS1, hPMS2, hMSH3 and hMSH6.
      Mutations in these genes allow mistakes in tumor suppressor genes and oncogenes
      to accumulate which eventually leads to cancer. The founder of an HNPCC family in
      the Creighton University Hereditary Cancer Institute database was known to
      produce truncated hMLH1 protein, a product of one of the aforementioned mismatch
      repair genes. Lymphoblasts were isolated from ten members of this HNPCC family
      (six affected and four unaffected) and two persons from outside this family (both
      unaffected controls). RNA and DNA were purified from these lymphoblasts which had
      been transformed by the Epstein-Barr virus (EBV). The hypothesis was that a
      mutation in the hMLH1 gene perpetuated defects in its mRNA and functional
      protein. hMLH1 RNA transcripts were detected in reverse transcriptase polymerase
      chain reactions (RT-PCR) whereby total poly A(+) RNA was converted to a
      complementary DNA (cDNA), amplified using hMLH1 specific primers, purified and
      cycle sequenced. Likewise, DNA was employed as template for PCR amplification of
      hMLH1 exons; PCR products were then directly cycle sequenced. Affected family
      members were found to produce hMLH1 mRNA lacking exons 6 and 7 (and wild-type
      mRNA). A splicing mutation at 546--2 (two bases 5' to exon 7) was located in the
      genomic DNA samples from the six family members with the HNPCC phenotype. This
      mutation caused deletion of exon 7 from the mRNA. None of the four unaffected
      family members or the two unaffected persons outside of this family had the above
      defects in their hMLH1 mRNA and DNA.

PMID- 12052502
TI  - Effect of SCID mutation on the occurrence of mouse Pc-1 (Ms6-hm) germline
      mutations.
AB  - Mouse Pc-1 (Ms6-hm) is a hypervariable minisatellite locus that is unstable
      during intergenerational transmission. This hyper-instability of Pc-1 is useful
      for detecting germline mutation using a small number of experimental animals,
      although its molecular mechanism has not yet been elucidated. We examined the
      effect of severe combined immune deficiency (SCID) mutation on the spontaneous
      germline mutation at the Pc-1 locus using the CB17 mouse strain. Our results
      showed that the frequency of spontaneous germline mutation at Pc-1 in the
      offspring of wild-type parents was 9.7%. In F1 between SCID male and wild-type
      female, however, the frequency of germline mutation was drastically increased to
      42.3%. When SCID female mice were mated with wild-type male, the frequency of
      germline mutation in F1 was slightly increased to 13.6%. These results suggest
      that DNA protein kinase catalytic subunit (DNA-PKcs), deficiency of which causes
      SCID mutation, plays an important role in the stable transmission of a genome
      containing hypervariable tandem repeats to progeny in male germ cells.

PMID- 12052503
TI  - Mosaic AZF deletions and susceptibility to testicular tumors.
AB  - We tested for azoospermia factor (AZF) deletions 17 loci corresponding to AZF
      subintervals a-d in 17 cases of testicular tumors occurring in Finns. While DNA
      samples from 48 CEPH and 32 Finnish males showed no deletions, patients with
      testicular cancer displayed AZF deletion mosaicisms in various non-tumor tissues
      (13 cases) and specific deletion haplotypes in tumor tissues (10 cases). Two of
      the cases with AZF deletions were testicular non-Hodgkin lymphomas indicating
      that Y-microdeletions appear also in malignancies other than seminoma and non
      seminoma tumors. In good agreement with this assumption, we detected one AZF
      deletion in normal cells from 1 of 5 HNPCC cases, heterozygous for an MLH1
      mutation. We propose that AZF deletions occur in early embryogenesis due to
      mutations of TSPY, mismatch repair (MMR), or X-specific genes. Since fathers of
      testicular, tumor cases did not exhibit AZF deletions, we assumed they were not
      carriers of the mutation inducing AZF deletion-mosaicisms. Therefore, tumor cases
      should have received the MMR gene or X mutations via the maternal lineage, or for
      the case of TSPY and MMR genes via a sperm carrying a mutation occurred in the
      paternal germ-cell line. We consider AZF microdeletions in non-tumor cells to be
      part of a broader pattern of chromosome instability producing susceptibility to
      testicular tumors. Clonal transformation and expansion of one of these tumor
      susceptible cell lineages give rise to testicular tumors showing genome anomalies
      characteristic of testicular cancers (i12p, LOH and genetic imbalance for various
      autosomal regions, Y- and autosomal MSI, specific AZF deletion haplotypes).

PMID- 12052504
TI  - Chromosomal response of human lymphocytes to streptozotocin.
AB  - The induction of chromosomal aberrations (CAs) and sister-chromatid exchanges
      (SCEs) by the methylating agent streptozotocin (STZ) and the effect of this
      compound on mitotic index (MI) and cell cycle progression in human lymphocytes
      were investigated. Unstimulated (G(0)) or cycling lymphocytes derived from whole
      blood or purified lymphocyte cultures were pulse-treated with increasing doses of
      STZ for 0.5-24h. Induction of CAs by STZ was only observed in cycling lymphocytes
      derived from whole blood cultures (WBC) (P<0.05). On the contrary, STZ produced a
      significant and dose-response increase in the yield of SCEs in unstimulated as
      well as cycling lymphocytes (P<0.05). In addition, STZ induced a dose-dependent
      decrease in the MI but had a slight effect on cell cycle progression. These
      results suggest that SCEs are the most sensitive endpoint for evaluating the
      chromosomal effects of STZ on these cells.

PMID- 12052505
TI  - A mouse kidney cell line with a G:C --> C:G transversion mutator phenotype.
AB  - We report the identification of a mouse kidney epithelial cell line (K435) in
      which G:C-->C:G transversion mutations occur at an elevated rate and are the
      predominant spontaneous events observed at the selectable Aprt locus. Of three
      genotoxins tested, ultraviolet radiation (UV), ionizing radiation, and hydrogen
      peroxide, only UV exposure was able to alter the spectrum of small mutational
      events. To determine if the G:C-->C:G mutator phenotype was due to a deficiency
      in the mismatch repair pathway, the K435 cells were tested for resistance to 6
      thioguanine, cisplatin, and MNNG. Although the K435 cells were as resistant to 6
      thioguanine and cisplatin as Pms2 and Mlh1 null kidney cells, they were
      hypersensitive to MNNG. Moreover, the K435 cells do not exhibit microsatellite
      instability, a hallmark of mismatch repair deficiency. These results suggest that
      a novel mechanism, which does not include a classical deficiency in mismatch
      repair, accounts for the G:C-->C:G mutator phenotype.

PMID- 12052506
TI  - Base-change mutations induced by various treatments of Bacillus subtilis spores
      with and without DNA protective small, acid-soluble spore proteins.
AB  - Previous work has shown that spores of wild-type Bacillus subtilis are more
      resistant to killing by dry and wet heat, low vacuum lyophilization and hydrogen
      peroxide than are spores lacking the majority of their DNA protective alpha/beta
      type small, acid-soluble spore proteins (SASP) (termed alpha(-)beta(-) spores).
      These four treatments kill alpha(-)beta(-) spores in large part by DNA damage
      with accompanying mutagenesis, but only dry heat kills wild-type spores by DNA
      damage and mutagenesis. DNA sequence analysis of nalidixic acid-resistant
      (nal(r)) mutants generated by these treatments has now shown that the nal(r)
      mutations are base changes in the gyrA gene that encodes one subunit of DNA
      gyrase. Analysis of the DNA sequence of the gyrA gene in a large number of nal(r)
      mutants also indicates that: (1) base changes induced by hydrogen peroxide and
      wet heat in alpha(-)beta(-) spores are similar to those in spontaneous nal(r)
      mutants with only a few notable differences; (2) base changes induced by dry heat
      in wild-type spores and low vacuum lyophilization of alpha(-)beta(-) spores are
      similar, and include a high level of a tandem base change seen previously only in
      spores treated with very high vacuum and (3) base changes induced by
      lyophilization and dry heat are very different from those in spontaneous mutants
      in wild-type and alpha(-)beta(-) spores, which exhibit only one significant
      difference. While the initial DNA damage generated in spores by dry heat,
      lyophilization or high vacuum is almost certainly different than that generated
      by hydrogen peroxide or wet heat, the precise nature of the DNA damage remains to
      be determined.

PMID- 12052507
TI  - The function of trehalose biosynthesis in plants.
AB  - Trehalose (alpha-D-glucopyranosyl-1,1-alpha-D-glucopyranoside) occurs in a large
      variety of organisms, ranging from bacteria to invertebrate animals, where it
      serves as an energy source or stress protectant. Until recently, only few plant
      species, mainly desiccation-tolerant 'resurrection' plants, were considered to
      synthesise trehalose. Instead of trehalose, most other plants species accumulate
      sucrose as major transport sugar and during stress. The ability to synthesize
      sucrose has probably evolved from the cyanobacterial ancestors of plastids and
      may be linked to photosynthetic function. Although most plant species do not
      appear to accumulate easily detectable amounts of trehalose, the discovery of
      genes for trehalose biosynthesis in Arabidopsis and in a range of crop plants
      suggests that the ability to synthesise trehalose is widely distributed in the
      plant kingdom. The apparent lack of trehalose accumulation in these plants is
      probably due to the presence of trehalase activity. After inhibition of
      trehalase, trehalose synthesis can be detected in Arabidopsis. Since trehalose
      induces metabolic changes, such as an accumulation of storage carbohydrates,
      rapid degradation of trehalose may be required to prevent detrimental effects of
      trehalose on the regulation of plant metabolism. In addition, the precursor of
      trehalose, trehalose-6-phosphate, is probably involved in the regulation of
      developmental and metabolic processes in plants.

PMID- 12052508
TI  - Lectins from seeds of Crotalaria pallida (smooth rattlebox).
AB  - A lectin from the seeds of Crotalaria pallida (CPL), with an apparent molecular
      mass of 30 kDa, determined by SDS-polyacrylamide gel electrophoresis, showed
      human type A and B erythrocytes agglutination activity, which is inhibited by
      raffinose and galactose. The lectin requirement for divalent cation was
      demonstrated with EDTA/EGTA blocking hemagglutination activity. Although the N
      terminal amino acid sequence of CPL is identical to another lectin from
      Crotalaria striata, which is taxonomically synonymous to Crotalaria pallida,
      these lectins differ in amino acid composition and hemagglutination properties.

PMID- 12052509
TI  - Feedback regulation of beta-thujaplicin production and formation of its methyl
      ether in a suspension culture of Cupressus lusitanica.
AB  - Suspension cell cultures of Cupressus lusitanica produce beta-thujaplicin, a
      tropolone found mostly in Cupressaceae heartwood. The factors controlling beta
      thujaplicin accumulation in this cell culture system were investigated. Initial
      cell density of the cultures did not affect beta-thujaplicin levels, though
      initial addition of beta-thujaplicin suppressed its de novo production. When beta
      thujaplicin accumulation reached a certain level (ca. 40 mg/l) in the medium, the
      cultures seemed to cease beta-thujaplicin production. However, beta-thujaplicin
      productivity was restored when the beta-thujaplicin-containing medium was
      exchanged for fresh medium; the formation of 2-methoxy-6-(methylethyl)cyclohepta
      2,4,6-trien-1-one, an isomer of methylated beta-thujaplicin, in medium was also
      observed. These results suggest that beta-thujaplicin synthesis was regulated by
      product feedback mechanism in this cell line, and that excess accumulation of
      beta-thujaplicin is relieved by conversion of beta-thujaplicin to its methyl
      ether.

PMID- 12052510
TI  - Differential incorporation of 1-deoxy-D-xylulose into (3S)-linalool and geraniol
      in grape berry exocarp and mesocarp.
AB  - In vivo feeding experiments with [5,5-(2)H(2)]mevalonic acid lactone (MVL) and
      [5,5-(2)H(2)]-1-deoxy-D-xylulose (DOX) indicate that the novel mevalonate
      independent 1-deoxy- D-xylulose 5-phosphate/2C-methyl- D-erythritol 4-phosphate
      (DOXP/MEP) pathway is the dominant metabolic route for monoterpene biosynthesis
      in grape berry exocarp and mesocarp and in grape leaves. The highly uneven
      distribution of the monoterpene alcohols (3S)-linalool and geraniol between
      leaves, berry exocarp and berry mesocarp can be attributed to a compartmentation
      of monoterpene metabolism. In grape berries incorporation of [5,5-(2)H(2)]-DOX
      into geraniol is mainly restricted to the exocarp, whereas (3S)-linalool
      biosynthesis can be detected in exocarp as well as in mesocarp tissue. The
      results demonstrate that grape berries exhibit an autonomic monoterpene
      biosynthesis via the novel DOXP/MEP route throughout the ripening process.

PMID- 12052511
TI  - Immunohistochemical localization of agatharesinol, a heartwood norlignan, in
      Cryptomeria japonica.
AB  - Localization of a heartwood norlignan, agatharesinol, in Sugi (Japanese cedar,
      Cryptomeria japonica D. Don, Taxodiaceae) was investigated by
      immunohistochemistry. Immuno light microscopy showed that the contents of ray
      parenchyma cells were immunostained in heartwood but not in sapwood. The staining
      of the heartwood tissue was competitively inhibited by agatharesinol but not by
      other Sugi heartwood extractives, and was, furthermore, markedly reduced by pre
      extraction of the tissue with MeOH. These results indicated that the staining can
      be ascribed to the immunolabeling of agatharesinol in situ. The accumulations
      over the inner surface of some tracheid cell walls adjacent to the ray parenchyma
      cells were also immunolabeled, while the contents in axial parenchyma cells were
      not. In conclusion, agatharesinol was localized in the ray parenchyma cells in
      Sugi heartwood, and differences between the chemical structure of the contents of
      ray and axial parenchyma cells were also suggested.

PMID- 12052512
TI  - Increase of free cysteine and citric acid in plant cells exposed to cobalt ions.
AB  - Cobalt complexation was investigated in a suspension cell culture of the cobalt
      hyperaccumulator Crotalaria cobalticola. C. cobalticola cells were more tolerant
      towards cobalt ions than the suspension cells of the non-accumulators Rauvolfia
      serpentina and Silene cucubalus. While the concentration of various compounds
      increased in cells of C. cobalticola challenged with cobalt ions, phytochelatin
      biosynthesis was not induced. Instead, the exposure to cobalt ions resulted in
      the increase of citrate and cysteine in cells. Size exclusion chromatography
      demonstrated the co-elution of cobalt and cysteine in C. cobalticola cell
      extracts. A significant increase in cysteine was observed also in cells of R.
      serpentina and S. cucubalus when they were exposed to cobalt ions. These results
      suggest that free cysteine is involved in cobalt ion complexation in plant cells.

PMID- 12052513
TI  - Aromadendrane transformations by Curvularia lunata ATCC 12017.
AB  - The naturally occurring sesquiterpene squamulosone (1), isolated from Hyptis
      verticillata (Labiatae), was synthetically reduced to five analogues that were
      identified as (1S,10S)-9alpha-hydroxy-allo-aromadendrane (2), (1R,10R)-9beta
      hydroxyaromadendrane (3), (1S,10S)-allo-aromadendran-9-one (4), (1R,10R)
      aromadendran-9-one (5) and aromadendra-1,9-diene (6). Each congener was incubated
      with the fungus Curvularia lunata ATCC 12017 in two different growth media. All
      the substrates except the deoxy compound 6 underwent a simple redox reaction.
      Ketone 5 additionally experienced remote hydroxylation while analogue 6,
      possessing a conjugated diene system, was most extensively metabolised. The
      substrates and products presented here, but one, are all novel.

PMID- 12052514
TI  - Movement to bark and metabolism of xylem cytokinins in stems of Lupinus
      angustifolius.
AB  - Following uptake of [(3)H]zeatin riboside and [(3)H]dihydrozeatin riboside by
      girdled lupin (Lupinus angustifolius L.) stems via the transpiration stream,
      rapid lateral movement of the radioactivity from xylem to bark was observed.
      Short-term studies with intact stems, and other studies with excised stem
      tissues, revealed that the ribosides and/or the corresponding nucleotides were
      the cytokinin forms which actually moved into the bark tissues. Relative to
      cytokinin metabolism in xylem plus pith, metabolism in bark was both more rapid
      and more complex. Riboside cleavage and formation of the O-acetylzeatin and O
      acetyldihydrozeatin ribosides and nucleotides were almost completely confined to
      bark tissues. Exogenous (3)H-labelled O-acetylzeatin riboside was converted to
      zeatin riboside in bark tissue, but the presence of the acetyl group suppressed
      degradation to adenine metabolites. The sequestration and modification of xylem
      cytokinins by stem tissues probably contributes significantly to the cytokinin
      status of the shoot. New cytokinins identified by mass spectrometry in lupin
      were: O-acetyldihydrozeatin 9-riboside, a metabolite of exogenous dihydrozeatin
      riboside in stem bark; O-methylzeatin nucleotide and O-methyldihydrozeatin 9
      riboside, metabolites of endogenous cytokinins in stem bark; O-methylzeatin
      nucleotide and O-methylzeatin 9-riboside, metabolites of exogenous zeatin
      riboside in excised pod walls.

PMID- 12052515
TI  - Chemotaxonomy of the tribe Antidesmeae (Euphorbiaceae): antidesmone and related
      compounds.
AB  - Selected species of the tribe Antidesmeae (Euphorbiaceae, subfamily
      Phyllanthoideae) have been screened for antidesmone occurrence and its content by
      quantitative HPLC (UV) and qualitative LC-MS/MS analysis. The LC-MS analysis
      allowing the additional detection of 17,18-bis-nor-antidesmone, 18-nor
      antidesmone, 8-dihydroantidesmone and 8-deoxoantidesmone was carried out in the
      selected reaction monitoring (SRM) mode. Leaf material from herbarium specimens
      of 13 Antidesma spp., Hyeronima alchorneoides and Thecacoris stenopetala (all
      subtribe Antidesminae), as well as Maesobotrya barteri, Aporosa octandra (both
      Scepinae) and Uapaca robynsii (Uapacinae) were analysed. Additionally, freshly
      collected samples of different plant parts of two Antidesma spp. were
      investigated to ensure the significance of the results on herbarium specimens and
      to compare the antidesmone content in bark, root and leaves. Antidesmone could be
      unambiguously identified in 12 of 13 Antidesma spp., as well as in the two other
      investigated genera of subtribe Antidesminae, in levels of up to 65 mg/kg plant
      dry weight. Antidesmone was not found in specimens from other subtribes.
      Antidesmone-derived compounds occur in much lower concentrations than
      antidesmone.

PMID- 12052516
TI  - Lipid and fatty acid composition of the green oleaginous alga Parietochloris
      incisa, the richest plant source of arachidonic acid.
AB  - We have hypothesized that among algae of alpine environment there could be
      strains particularly rich in long chain polyunsaturated fatty acids (LC-PUFA).
      Indeed, the chlorophyte (Trebuxiophyceae) Parietochloris incisa isolated from Mt.
      Tateyama, Japan, was found to be the richest plant source of the pharmaceutically
      valuable LC-PUFA, arachidonic acid (AA, 20:4omega6). The alga is also extremely
      rich in triacylglycerols (TAG), which reaches 43% (of total fatty acids) in the
      logarithmic phase and up to 77% in the stationary phase. In contrast to most
      algae whose TAG are made of mainly saturated and monounsaturated fatty acids, TAG
      of P. incisa are the major lipid class where AA is deposited, reaching up to 47%
      in the stationary phase. Except for the presence of AA, the PUFA composition of
      the chloroplastic lipids resembled that of green algae, consisting predominantly
      of C(16) and C(18) PUFAs. The composition of the extrachloroplastic lipids is
      rare, including phosphatidylcholine (PC), phosphatidylethanolamine (PE) as well
      as diacylglyceryltrimethylhomoserine (DGTS). PC and PE are particularly rich in
      AA and are also the major depots of the presumed precursors of AA, l8:3omega6 and
      20:3omega6, respectively.

PMID- 12052517
TI  - Iridoid glucosides from roots of Vietnamese Paederia scandens.
AB  - Four iridoid glucosides, three of which are dimeric were isolated from the
      methanol extract of roots of Vietnamese Paederia scandens (Lour) Merrill together
      with the five known glucosides, paederoside, asperuloside, paederosidic acid,
      asperulosidic acid and geniposide. Seven sulfur-containing iridoid glucosides
      were also isolated. The structures of the iridoid glucosides were determined by a
      combination of high-resolution NMR, MS, IR and UV spectra, and chemical reaction
      such as acetylation.

PMID- 12052518
TI  - Flavonolignans from Hyparrhenia hirta.
AB  - Leaves of Hyparrhenia hirta yielded the rare diastereoisomeric flavonolignans
      tricin 4'-O-(erythro-beta-guaiacylglyceryl) ether and tricin 4'-O-(threo-beta
      guaiacylglyceryl) ether together with their 7-O-glucosides, which are the first
      flavonolignan glycosides to be isolated as natural products. A complete set of
      (1)H and (13)C NMR resonance assignments obtained for both flavonolignan
      aglycones indicates the need for revision of data published previously for these
      compounds and for a reassessment of their original stereochemical designation.

PMID- 12052519
TI  - (4-->6)-Coupled proteracacinidins and promelacacinidins from Acacia galpinii and
      Acacia caffra.
AB  - The series of naturally occurring proanthocyanidins with 7,8-dihydroxylated A
      rings is extended by identification of the proteracacinidins epioritin-(4beta-
      >6)-oritin-4alpha-ol, epioritin-(4beta-->6)-ent-oritin-4alpha-ol, ent-oritin
      (4beta-->6)-epioritin-4alpha-ol, ent-oritin-(4beta-->6)-oritin-4alpha-ol, ent
      oritin-(4alpha-->6)-epioritin-4alpha-ol, ent-oritin-(4alpha-->6)-oritin-4alpha
      ol, ent-oritin-(4alpha-->6)-epioritin-4beta-ol, the 'mixed' pro-teracacinidins/
      melacacinidins epioritin-(4beta-->6)-epimesquitol-4alpha-ol, epioritin-(4beta-
      >6)-epimesquitol-4beta-ol and epimesquitol-(4beta-->6)- epioritin-4alpha-ol, and
      the promelacacinidin epimesquitol-(4beta-->6)-epimesquitol-4beta-ol.

PMID- 12052521
TI  - Xanthones from the heartwood of Garcinia mangostana.
AB  - Twelve xanthones were isolated from the hexane extract of the heartwood of
      Garcinia mangostana from Myanmar. Their structures were determined using 1D and
      2D NMR techniques

PMID- 12052520
TI  - Flavonoids from two Lonchocarpus species of the Yucatan Peninsula.
AB  - Leaves, stem bark and root of Lonchocarpus xuul and Lonchocarpus yucatanensis
      were studied separately. A chalcone, 2',4-dimethoxy-6'-hydroxylonchocarpin (),
      and the flavones 5,4'-dihydroxy-3'-methoxy-(6:7)-2,2-dimethylpyranoflavone (2)
      and 5,4'-dimethoxy-(6:7)-2,2-dimethylpyrano-flavone (3), together with the known
      carpachromene (4), were isolated from the leaves of both species. Similarly, the
      previously reported flavans xuulanin (5) and 3beta-methoxyxuulanin (6), together
      with the novel 3beta,4beta,5-trimethoxy-4'-hydroxy-(6:7)-2,2-dimethylpyranoflavan
      (7), 3-hydroxy-4,5-dimethoxy-(6:7)-2,2-dimethyl-pyranoflavan (8), and 3,4
      dihydroxy-5-methoxy-(6:7)-2,2-dimethylpyranoflavan (10), were isolated from the
      stem bark and root of both species. Finally, the known 2',4'-dihydroxy-3'-(3
      methylbut-2-enyl) chalcone (13) was obtained from the root of L. xuul only. The
      structures of the various metabolites were established by interpretation of their
      spectroscopic data.

PMID- 12052524
TI  - Neurosteroids enhance bandpass filter characteristics of the rat Schaffer
      collateral-to-CA1 synapse.
AB  - Neurosteroids are important modulators of synaptic activity in the mammalian
      central nervous system. We have shown previously that the neurosteroid,
      pregnenolone sulfate (PREGS) enhances paired-pulse facilitation at the Schaffer
      collateral-to-CA1 synapse in rat hippocampal slices. Here we show that PREGS
      enhances the facilitation of postsynaptic potentials (PSPs) during a 300 ms train
      of repetitive stimuli at frequencies between 10 and 50 Hz. At higher or lower
      frequencies, however, PREGS does not affect the PSPs produced by repetitive
      stimuli. This enhancement of the bandpass filtering characteristic of a central
      synapse by a naturally occurring neurosteroid could selectively influence
      transmission at bursting or other highly active synapses.

PMID- 12052525
TI  - Expression of alpha-synuclein, the precursor of non-amyloid beta component of
      Alzheimer's disease amyloid, in human cerebral blood vessels.
AB  - The non-amyloid beta component of Alzheimer's disease amyloid (NAC) is detected
      in cerebral amyloid angiopathy; and the precursor of NAC is now known to be
      identical to alpha-synuclein (alpha-S), a major component of Lewy bodies in
      Parkinson's disease. We studied if cerebral vascular cells express alpha-S.
      Immunohistochemical studies of human cerebral tissues from control and cerebral
      amyloid angiopathy patients revealed the expression of alpha-S in vascular
      endothelial and smooth muscle cells. Then we studied the expression of alpha-S in
      vitro using cultures of vascular cells. Cultures of human umbilical vein
      endothelial cells and umbilical artery smooth muscle cells were found to
      constitutively express alpha-S messenger RNA and protein. alpha-S is normally
      expressed in vascular cells and may play some physiological role in the vascular
      wall.

PMID- 12052526
TI  - Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the
      phosphorylation of retinoblastoma protein: relevance for neurodegeneration.
AB  - Mutations in the presenilin 1 (PS1) gene have been associated to familial
      Alzheimer disease although the exact pathogenic mechanism is unclear. We report
      that stable overexpression of wild type PS1 led to a decrease in cyclin-dependent
      kinase 4 (CDK 4) activity and retinoblastoma tumor suppressor protein (pRb)
      phosphorylation that correlated with decreased levels of beta-catenin and cyclin
      D1. PS1 mutant D385A also precipitated a similar effect suggesting that gamma
      secretase cleavage is not essential for PS1-mediated CDK 4 inhibition. We
      postulate that PS1 overexpression may balance the hyperphosphorylation of pRb
      associated with death of post mitotic neurons after injury.

PMID- 12052527
TI  - Quantal endplate currents from newborn to adult mice and the switch from
      embryonic to adult channel type.
AB  - Quantal endplate currents (qEPCs) were recorded extracellularly by a macropatch
      electrode from excised diaphragms of mice. During the first 3 days after birth,
      the mean rise time t(r) was 0.5 ms (0.1-0.9 peak, 20 degrees C). Double
      exponential, amplitude-weighted fits of the decay discerned almost equally
      abundant components tau(1)' approximately equal to 6 ms and tau(2)' approximately
      equal to 9 ms. Beginning on day 3, on days 4 and 5 after birth both t(r) and the
      tau' dropped. Further decreasing slowly, adult values were reached at day 8, with
      t(r) approximately equal to 0.3 ms, tau(1)' approximately equal to 2 ms and a
      very weak tau(2)' approximately equal to 6 ms component. When compared to the
      kinetics of fetal channels, the tau(1)' and tau(2)' of up to 3 day qEPCs could
      correspond to the short and long splice variants of the fetal channel type. The
      tau(1)' of adult muscles of 2 ms agrees well with the burst durations of adult
      channels while a weak longer tau(2)' component may represent 'extrasynaptic'
      channels. The long t(r) of very young mice may correspond to the relatively slow
      rise of channel currents elicited by ACh pulses in mouse myoballs.

PMID- 12052528
TI  - Release of beta-endorphin from adrenal gland to lower plasma glucose by the
      electroacupuncture at Zhongwan acupoint in rats.
AB  - We found that electroacupuncture (EA) at the Zhongwan acupoint released beta
      endorphin to induce an insulin-dependent hypoglycemia in rats. The present study
      investigated the source of beta-endorphin. EA at 2 Hz for 30 min in rats
      decreased plasma glucose that could be abolished by naloxone. A similar effect of
      EA was also observed in wild-type mice but disappeared in mu-opioid receptor
      knockout mice. Mediation of the mu(1)-opioid receptor is considered from the
      blockade of response to EA by naloxonazine in rats. Otherwise, adrenalectomy
      abolished not only the hypoglycemic response to EA in rat and mouse but also the
      increase of plasma beta-endorphin and insulin by EA in rats. In conclusion, the
      increase of plasma beta-endorphin by EA at 2 Hz is mainly from the adrenal gland.

PMID- 12052530
TI  - Body image distortion reveals amygdala activation in patients with anorexia
      nervosa -- a functional magnetic resonance imaging study.
AB  - In anorexia nervosa patients, body image distortion is a core and often
      persistent symptom, which continues to pose a risk for relapse even after weight
      recovery. Using functional magnetic resonance imaging (fMRI) in combination with
      a computer-based life image distortion technique, we stimulated female anorectic
      patients and healthy controls with digital pictures of their own body image,
      individually distorted by themselves. In anorectic patients, stimulation with
      their own body image was associated with activation in the right amygdala, the
      right gyrus fusiformis and the brainstem region. Our preliminary findings
      indicate an activation of the brain's 'fear network' and underscore the need for
      examination of body image distortions in anorectic patients with a fMRI design to
      further evaluate the course of this disturbance in a longitudinal approach.

PMID- 12052529
TI  - Breakdown of choline-containing phospholipids in rat brain during severe weight
      loss.
AB  - Recent investigations in human anorectic patients indicated changes of brain
      choline metabolism. We used starved rats to investigate possible changes of brain
      choline metabolites during severe weight loss. Reductions of body weight by 15,
      30 and 45% resulted in significant decreases of cerebral phosphatidylcholine and
      sphingomyelin levels. Concomitantly, the brain tissue content of
      glycerophosphocholine was increased while phosphocholine and free choline were
      unchanged. We conclude that severe weight loss is accompanied by phospholipase
      activation and breakdown of choline-containing phospholipids in the brain.

PMID- 12052531
TI  - Inflammation-induced up-regulation of neurokinin 1 receptors in rat glabrous
      skin.
AB  - Peripheral inflammation sensitizes primary afferent fibers causing lowered
      thresholds and increased responses to noxious input. One mechanism for
      sensitization might be increased expression of receptors whose activation results
      in nociceptor activity. Accordingly, the present study demonstrates that 15.6% of
      unmyelinated primary afferent axons in rat glabrous skin express the neurokinin 1
      (NK1) receptor. At 48 h following hindpaw inflammation with complete Freund's
      adjuvant, the proportion of unmyelinated axons expressing NK1 receptors
      significantly increases to 23.6%. This implies a considerable upregulation of NK1
      receptor synthesis in the dorsal root ganglia with subsequent transport to
      peripheral nociceptive terminals. Antagonizing peripheral NK1 receptors locally
      would be effective in reducing inflammatory pain by reducing neural transduction
      in NK1-expressing nociceptors as well as lessening the inflammatory vascular
      effects of peripheral substance P.

PMID- 12052532
TI  - The myeloperoxidase gene in Alzheimer's disease: a case-control study and meta
      analysis.
AB  - Myeloperoxidase (MPO) presence has been demonstrated in microglia associated with
      senile plaques, and contributes to Alzheimer's disease (AD) pathology through
      oxidation-induced damage. Recently, a functional biallelic (G/A) polymorphism in
      the promotor region (-463) of the MPO gene has been associated with
      susceptibility to AD, but the reports of this association have been inconsistent.
      A case-control study utilizing a clinically well-defined group of 315 sporadic AD
      patients and 327 control subjects was performed to test this association. The
      current study does not demonstrate any significant difference in MPO genotype or
      allele frequencies between AD patients and controls. A meta-analysis of all
      studies available gave a non-significant (P=0.83) odds ratio of 1.02 for the MPO
      GG genotype. Our study in the Spanish population as well as the meta-analysis
      argue against the hypothesis that the MPO gene is causally related to AD.

PMID- 12052533
TI  - Characterization of three novel isoforms of the metabotrobic glutamate receptor 7
      (GRM7).
AB  - The G protein-coupled metabotropic glutamate receptors (GRMs) consist of a family
      of eight members. Structural and functional diversity of this receptor family is
      achieved by the existence of alternative exon usage generally affecting the
      immediate carboxy-terminus. This region is known to specifically interact with
      defined proteins thus mediating various receptor functions such as intracellular
      signal transduction, axonal targeting and synaptic clustering. For GRM7 two
      isoforms, GRM7_v1 and GRM7_v2, have previously been characterized. In the present
      study, we have identified additional splicing variants involving the 3' end of
      the GRM7 coding sequence and resulting in three putative novel isoforms, termed
      GRM7_v3, GRM7_v4, GRM7_v5. While most variants are expressed in brain and retina
      with varying abundance, expression of GRM7 isoforms in non-neuronal tissues
      appears to be restricted to isoforms v3 and v4. This may suggest that particular
      functional properties associated with the various GRM7 subtypes could be
      reflected by their tissue- and/or cell-specific expression.

PMID- 12052534
TI  - The involvement of nitric oxide on the adenosine A(2) receptor-induced
      cardiovascular inhibitory responses in the posterior hypothalamus of rats.
AB  - This study was performed to investigate the putative relationship between nitric
      oxide (NO) and adenosine A(2) receptors on central cardiovascular regulation in
      the posterior hypothalamus of rats. Posterior hypothalamic injection of drugs was
      performed in anesthetized, artificially ventilated male Sprague-Dawley rats.
      Injection of adenosine A(2) receptor agonist 5'-(N-cyclopropyl)
      carboxamidoadenosine (CPCA; 1, 2 and 5 nmol) produced a dose-dependent decrease
      of blood pressure and heart rate. Pretreatment with adenosine A(2) receptor
      antagonist 3,7-dimethyl-1-propargylxanthine (10 nmol) blocked the depressor and
      bradycardiac effects of CPCA (5 nmol). Pretreatment with soluble guanylate
      cyclase inhibitor LY-83,583 (5 nmol) attenuated the depressor and bradycardiac
      effects of CPCA (5 nmol). In addition, pretreatment with NO synthase inhibitor
      N(G)-nitro-L-arginine methyl ester (40 nmol) attenuated the depressor and
      bradycardiac responses of CPCA (5 nmol). These results suggest that adenosine
      A(2) receptor in the posterior hypothalamus plays an inhibitory role in central
      cardiovascular regulation and that NO participates in the inhibitory response
      induced by adenosine A(2) receptor stimulation in the posterior hypothalamus.

PMID- 12052535
TI  - Time-of-flight-, phase contrast and contrast enhanced magnetic resonance
      angiography for pre-interventional determination of aneurysm size, configuration,
      and neck morphology in an aneurysm model in rabbits.
AB  - We describe three different magnetic resonance (MR)-angiography techniques to
      evaluate aneurysm size, configuration, and neck morphology of experimentally
      created aneurysms in a rabbit model. In five New Zealand White rabbits an
      aneurysm was created by endovascular occlusion of the right common carotid artery
      (CCA) using a pliable balloon and subsequent endoluminal incubation of elastase
      within the proximal CCA above the balloon and distal ligation of the vessel. In
      all animals, time-of-flight (TOF), phase contrast and contrast enhanced (CE) MR
      angiographies (MRA) were performed and compared to conventional digital
      subtraction angiography results. We found, that aneurysms are best visualized
      employing CE MRA, however, neck morphology was also found to demonstrate
      interpretable results when evaluating the axial source data of the TOF MRA. The
      animal model we used can be employed for testing endovascular devices such as new
      coil material, or covered stents. The described MRA techniques might then be
      helpful for pre-interventional planning and maybe even for the follow-up of the
      thus treated aneurysms.

PMID- 12052536
TI  - The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human
      neuroblastoma cells.
AB  - The E693G (Arctic) mutation of the amyloid precursor protein was recently found
      to lead to early-onset Alzheimer's disease in a Swedish family. In the present
      study, we report that the Arctic mutation decreases cell viability in human
      neuroblastoma cells. The cell viability, as measured by the MTT assay and
      propidium iodide staining, was further compromised following exposure to calcium
      ionophore A23187, microtubule-binding colchicine or oxidative stress inducer
      hydrogen peroxide. The manner of cell death was found to be apoptotic. During
      apoptosis, cells with the Arctic mutation also decreased their secretion of beta
      secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic
      stress in cells with the Arctic mutation most likely contributes to the
      pathogenic pathway leading to Alzheimer's disease.

PMID- 12052537
TI  - Increased monoamine oxidase messenger RNA expression levels in frontal cortex of
      Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder and the most common
      cause of dementia in the industrialised world. The two monoamine oxidase (MAO)
      enzymes, monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB), are important
      in the metabolism of monoamine neurotransmitters. AD and ageing have been shown
      to increase enzyme activity for both MAOA and MAOB. An increase (rather than
      decrease) of enzyme activity is a rare event in a disease that results in a
      decrease in the number of cells in the brain. The mechanism, transcriptional or
      post-transcriptional, responsible for the increase in protein activity, is not
      known. In this study, we investigate for the first time the messenger RNA (mRNA)
      expression levels of both MAOA and MAOB in 246 cortical brain samples obtained at
      autopsy from 62 AD patients and 61 normal controls. We found a significant
      increase in mRNA levels for both MAOA (P=0.001) and MAOB (P=0.002) in disease
      brain tissue. This indicates that both MAO enzymes might be important in the
      progression of AD.

PMID- 12052538
TI  - Low-frequency stimulation of the kindling focus delays basolateral amygdala
      kindling in immature rats.
AB  - Stimulation of deep brain sites is a new approach for treatment of intractable
      seizures. In adult rats, low-frequency stimulation (LFS; 1-3 Hz) of the kindling
      site interferes with the course of kindling epileptogenesis. In this study we
      determined whether the LFS will be effective against the fast kindling in the
      basolateral amygdala in immature, 15 day old rats. LFS (15 min of 1 Hz
      stimulation) was applied after each of the 1 s, 60 Hz kindling stimulus. LFS
      suppressed afterdischarge duration and seizure stage throughout the course of
      kindling, which indicates a strong antiepileptogenic potential. As the kindling
      and LFS stimulation patterns are similar to those used for induction of long-term
      potentiation and long-term depression (LTD), respectively, LTD or depotentiation
      may play a role in the mechanism of action.

PMID- 12052539
TI  - Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in
      brains of patients with Down syndrome.
AB  - The gene encoding the beta-site amyloid precursor protein cleaving enzyme 2
      (BACE2) has been determined to be located on the long arm of chromosome 21 at
      21q22.3. BACE2 cleaves the amyloid precursor protein at the beta-secretase site
      and is thought to contribute to amyloid beta protein production. In the present
      study, changes in the expression of BACE2 were investigated immunohistochemically
      in the frontal cortex of patients with Down syndrome (DS). The immunoreactivity
      for BACE2 was detected in neurofibrillary tangle-bearing neurons from the elderly
      DS brains with Alzheimer-type neuropathology, but were not detected in those of
      DS brains without Alzheimer-type neuropathology or of control brains of any age.
      This suggests the possibility that the elevated expression of BACE2 is involved
      in the Alzheimer-type neuropathology of DS.

PMID- 12052540
TI  - Association of interleukin-1 beta polymorphisms with idiopathic Parkinson's
      disease.
AB  - Activated microglia surround degenerating substantia nigra neurons in Parkinson's
      disease (PD). Such microglia produce high levels of interleukin-1 beta (IL-1
      beta) and interleukin-1 alpha (IL-1 alpha). T and C alleles exist for the IL-1
      beta-511 regulatory region as well as for the IL-1 alpha-889 regulatory region.
      The T genotypes of both have been reported to increase the risk of Alzheimer's
      disease (AD) (Arch. Neurol. 58 (2001) 1790). Since the lesions of PD and AD have
      similar neuroinflammatory characteristics (Neurology 38 (1988) 1285), we
      genotyped 100 PD and 100 control postmortem brains for the same polymorphisms. We
      found a significant increase of the IL-1 beta T genotype in PD cases compared
      with controls (chi(2)=9.65, P=0.0019). A significant increase was not found for
      the IL-alpha T genotype (chi(2)=1.32, P=0.23), although there was a trend towards
      more frequent expression of the T allele.

PMID- 12052541
TI  - Polymorphisms in the interleukin-1 alpha and beta genes and the risk for
      Parkinson's disease.
AB  - Several lines of evidence indicate that immune mechanisms are involved in the
      pathogenesis of neurodegenerative disorders. Activated immunocompetent cells and
      inflammatory cytokines are present in affected brain regions in patients with
      Alzheimer's (AD) and Parkinson's disease (PD). For AD biochemical and
      pathological data are supported by genetic studies identifying risk alleles for
      polymorphisms in regulatory regions of the interleukin-1 alpha (IL-1 alpha-889)
      and interleukin-1 beta (IL-1 beta-511) gene, respectively. The partially
      overlapping pathology and inflammatory reaction pattern between AD and PD led us
      to investigate these polymorphisms in a large sample of 295 German PD patients
      and 270 healthy controls. We found T in position -511 in the IL-1 beta gene more
      frequent in patients compared to controls (chi(2)=4.44, P=0.034). For the IL-1
      alpha-889 polymorphism no significant difference between patients and controls
      was observed.

PMID- 12052542
TI  - Bacterial anti-apoptotic activities.
AB  - Cell death by apoptosis is a common response to environmental stimuli and a
      frequent event in a multicellular organism. Not surprisingly, apoptosis is also
      found in microbial infections where it may contribute to progression and outcome.
      Perhaps less predictably, a number of bacteria have also been found to alleviate
      or even to inhibit apoptosis. Today we are at a point where our in some parts
      detailed knowledge of the molecular pathway to apoptosis allows us to probe
      situations in biology for the occurrence of apoptosis and to inquire into
      mechanisms of apoptosis induction and inhibition. In this brief article we will
      focus on anti-apoptotic activities exhibited by various bacteria. We will attempt
      to present the current knowledge on how the contact between mammalian and
      bacterial cell decrees resistance to apoptosis, what the respective contributions
      of the two partners are and how this interaction relates to the molecular path to
      apoptosis.

PMID- 12052543
TI  - Altamira cave Paleolithic paintings harbor partly unknown bacterial communities.
AB  - Since it has been reported that microorganisms can affect painting pigments,
      Paleolithic painting microbiology deserves attention. The present study is the
      first report on the bacterial colonization of the valuable Paleolithic paintings
      in the famous Altamira cave (Spain). One sample taken from a painting area in the
      Polychromes Hall was analyzed culture-independently. This was the first time
      microbiologists were allowed to take sample material directly from Altamira
      paintings. Identification methods included PCR amplification of 16S rRNA genes
      (16S rDNA) and community fingerprinting by denaturing gradient gel
      electrophoresis (DGGE). The applied approach gave insight into a great bacterial
      taxonomic diversity, and allowed the detection of unexpected and unknown bacteria
      with potential effects on the conservation of the painting. Regarding the number
      of 29 visible DGGE bands in the community fingerprint, the numbers of analyzed
      clones described about 72% of the phylogenetic diversity present in the sample.
      Thirty-eight percent of the sequences analyzed were phylogenetically most closely
      related to cultivated bacteria, while the majority (62%) were most closely
      related to environmental 16S rDNA clones. Bacteria identified in Altamira were
      related with sequence similarities between 84.8 and 99.4% to members of the
      cosmopolitan Proteobacteria (52.3%), to members of the Acidobacterium division
      (23.8%), Cytophaga/Flexibacter/Bacteroides phylum (9.5%), green non-sulfur
      bacteria (4.8%), Planctomycetales (4.8%) and Actinobacteria (4.8%). The high
      number of clones most closely related to environmental 16S rDNA clones showed the
      broad spectrum of unknown and yet to be cultivated bacteria in Altamira cave.

PMID- 12052545
TI  - Genetic heterogeneity of Campylobacter concisus determined by pulsed field gel
      electrophoresis-based macrorestriction profiling.
AB  - In order to investigate the genetic diversity of Campylobacter concisus to assist
      molecular typing studies, the use of macrorestriction profiling was examined. A
      suitable protocol was developed that included the use of formaldehyde
      pretreatment to prevent DNA degradation, and restriction enzyme NotI for pulsed
      field gel electrophoresis-based genotyping. Subsequently, 53 strains of C.
      concisus, principally from cases of diarrhoea in children, were examined. Fifty
      one distinct patterns were obtained, indicating the high discriminatory potential
      of the method. Patterns comprised between one and 14 restriction fragments, with
      type and reference strains of two well-defined genomospecies of oral and faecal
      origin containing six and 12 fragments respectively. Our results show that C.
      concisus is genetically diverse and suggest the species as currently defined to
      be a taxonomic continuum comprised of several genomospecies. The pulsed field gel
      electrophoresis typing method described here has considerable potential for
      molecular epidemiological studies of C. concisus and may be a useful adjunctive
      method for helping to resolve key taxonomic issues for this species.

PMID- 12052544
TI  - Substitution of Met-69 by Ala or Gly in TEM-1 beta-lactamase confer an increased
      susceptibility to clavulanic acid and other inhibitors.
AB  - In some inhibitor-resistant TEM-derived beta-lactamases, Met-69 is substituted by
      Leu, Ile or Val. Residue 69 is located in a region of strong structural
      constraints, at the beginning of H2 alpha-helix, and in the vicinity of B3 and B4
      beta-strands. Analysis of the three-dimensional structure of TEM-1 beta-lactamase
      suggests that alteration of the substrate-binding site can be produced by changes
      of the size of residue 69 side chain. Met-69 was substituted by alanine or
      glycine in TEM-Bs beta-lactamase (a TEM-1-related enzyme) using site-directed
      mutagenesis. The minimum inhibitory concentrations of the mutants compared with
      the wild-type revealed an increased susceptibility to beta-lactamase inhibitor
      beta-lactam combinations and to first-generation cephalosporins. Comparing the
      Met69Ala and Met69Gly beta-lactamases with TEM-Bs, K(m) constants of the mutants
      showed an increased affinity for most beta-lactams but the kcat for most
      substrates did not change substantially. Mutants also demonstrated lower IC50 for
      the three inhibitors (clavulanic acid, tazobactam and sulbactam). The two
      substitutions of the residue 69 by alanine and glycine had a noticeable effect on
      K(m) values of TEM-Bs beta-lactamase, and on affinity for beta-lactamase
      inhibitors.

PMID- 12052546
TI  - A 45-kDa acetylcholinesterase protoxin of Aeromonas hydrophila: purification and
      immunogenicity in fish.
AB  - A rabbit antiserum to the 15-kDa acetylcholinesterase toxin neutralised the
      lethal effect of the 15-kDa toxin of Aeromonas hydrophila when injected into
      trout. However, immunisation of fish with the 15-kDa toxoid failed to induce an
      antibody response, and a higher molecular mass form of this toxin was purified
      from the extracellular products with the aim of inducing an immune response in
      fish. The optimal conditions for production of extracellular products by A.
      hydrophila strain B32 were studied to increase the concentration of this
      protoxin. The extracellular products were fractionated by molecular exclusion
      chromatography to yield a purified protoxin with an estimated molecular mass of
      45 kDa by SDS-PAGE and which gave a positive reaction in Western blotting with
      the rabbit anti-15-kDa toxin serum. Since the 45-kDa protoxin showed lower
      specific acetylcholinesterase activity than the active 15-kDa toxin, the
      behaviour of the active site was studied using specific inhibitors. This 45-kDa
      protoxin was 13.3-fold less toxic than the 15-kDa toxin and induced antibody
      production in fish.

PMID- 12052547
TI  - A phosphate-stimulated NAD(P)+-dependent glyceraldehyde-3-phosphate dehydrogenase
      in Bacillus cereus.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme of central carbon
      metabolism, was studied in a Bacillus cereus strain isolated from the phosphate
      layer from Morocco. Enzymatic assays with cell extracts demonstrated that when
      grown on Luria-Bertani (LB) medium, B. cereus contains a major NAD+-dependent
      GAPDH activity and only traces of NADP+-dependent activity, but in cells grown on
      Pi-supplemented LB medium a strong increase of the NADP+-dependent activity, that
      became predominant, occurs concurrently with a GAPDH protein increase. Our
      results show that B. cereus possesses two GAPDH activities, namely NAD+- and
      NADP+-dependent, catalyzed by two enzymes with distinct coenzyme specificity and
      different phosphate regulation patterns. The finding of a phosphate-stimulated
      NADP+-dependent GAPDH in B. cereus indicates that this bacterium can modulate its
      primary carbon metabolism according to phosphate availability.

PMID- 12052548
TI  - Glutamate dehydrogenase of Halobacterium salinarum: evidence that the gene
      sequence currently assigned to the NADP+-dependent enzyme is in fact that of the
      NAD+-dependent glutamate dehydrogenase.
AB  - A GDH gene from Halobacterium salinarum has been cloned and sequenced and the
      publication assigns the sequence to the NADP+-glutamate dehydrogenase of this
      organism. We have expressed this gene in Escherichia coli and find that it
      encodes an NAD+-dependent glutamate dehydrogenase without activity towards NADP+.
      Further, peptide sequence from the two corresponding proteins supports the view
      that the deposited sequence is indeed that of the NAD+-dependent glutamate
      dehydrogenase. Sequence from the NAD+-dependent protein matches the published
      gene sequence, whereas sequence from the NADP+ glutamate dehydrogenase does not.

PMID- 12052549
TI  - Sphingomonas sp. strain KA1, carrying a carbazole dioxygenase gene homologue,
      degrades chlorinated dibenzo-p-dioxins in soil.
AB  - Hybridization analysis showed that a newly isolated carbazole (CAR)-degrading
      bacterium Sphingomonas sp. strain KA1 did not possess the gene encoding the
      terminal oxygenase component (carAa) of CAR 1,9a-dioxygenase at high homology
      (more than 90% identity) to that of another CAR-degrader, Pseudomonas
      resinovorans strain CA10. However, PCR experiments using the primers for
      amplifying the internal fragment of the carAa gene (810 bp for strain CA10)
      showed that a PCR product of unexpected size (1100 bp) was amplified. Sequence
      analysis revealed that this DNA region contained the portion of two possible
      ORFs, which showed moderate homology to CarAa and CarBa from strain CA10 (61% and
      40% identities at the amino acid level, respectively). Inoculation of strain KA1
      into dioxin-contaminated model soil resulted in 96% and 70% degradation of 2-mono
      and 2,3-dichlorinated dibenzo-p-dioxin, respectively, after 7-day incubation.

PMID- 12052550
TI  - ERIC- and REP-PCR amplify non-repetitive fragments from the genome of Drechslera
      avenae and Stemphylium solani.
AB  - In the present study, the homology relationships among fragments amplified by
      ERIC (Enterobacterial Repetitive Intergenic Consensus) and REP (Repetitive
      Extragenic Palindromic) primers in Drechslera avenae and Stemphylium solani
      causing leaf blotch and black spot of oats and leaf blight of cotton,
      respectively, were investigated by Southern hybridization followed by DNA
      sequencing. ERIC- and REP-PCR were performed for 24 isolates of D. avenae and 33
      isolates of S. solani. The banding patterns obtained were transferred to nylon
      membranes and a total of 16 fragments, four ERIC and four REP bands from each
      fungus, used as probes. The hybridization and DNA sequencing revealed a low
      degree of similarity among the bands indicating that the regions amplified by
      these primers are not repetitive and that the primers anneal at random regions in
      the genomes of D. avenae and S. solani.

PMID- 12052551
TI  - Characterization of regions of the cyanobacterial tRNA(pro) gene that affect the
      expression of a beta-glucuronidase reporter gene.
AB  - The E3 strong promoter-active fragment harbors the tRNA(pro) (GGG) gene upstream
      of the promoterless beta-glucuronidase (GUS) reporter gene in plasmid pKG-E3. The
      74-bp tRNA(pro) coding sequence contains two regions exhibiting strong homology
      to blocks A and B which are the split promoter elements of eukaryotic tRNA genes.
      Results in this study showed that the promoter region of tRNA(pro) gene located
      upstream of its coding sequence and harbored the putative -10 (TACATT) and -35
      (TTGGCA) regions which conformed to the Escherichia coli sigma(70) promoter.
      Differentiation of the 5' end of tRNA(pro)-GUS transcripts of pKG-E3 revealed
      that the true transcription initiation sites were located at positions -3, -4,
      and -6, while the processed sites were located at position +75, +76 and +78 with
      respect to the first nucleotide of the tRNA(pro) coding sequence. The presence of
      block A decreased GUS activity about three-fold, whereas block B and the 3' end
      of tRNA(pro) gene completely abolished GUS expression. However, the presence of
      full-length tRNA(pro) gene did not affect the GUS expression. Downstream of the
      tRNA(pro) coding sequence in chromosomal DNA contained a 32-bp stem-loop
      structure with a predicted DeltaG value of -21.7 kcal x mol(-1). The absence of
      this stem-loop structure downstream of the tRNA(pro) coding sequence in pKG-E3
      resulted in read-through transcription into the adjoining GUS gene.

PMID- 12052552
TI  - Energetics and kinetics of lactate fermentation to acetate and propionate via
      methylmalonyl-CoA or acrylyl-CoA.
AB  - Fermentation balances and growth yields were determined with various bacteria
      fermenting lactate to acetate plus propionate either via methylmalonyl-CoA or via
      acrylyl-CoA. All strains fermented lactate to acetate plus propionate at
      approximately a 1:2 ratio. Growth yields of Propionibacterium freudenreichii were
      more than twice as high as those of Clostridium homopropionicum or Veillonella
      parvula. Hydrogen was formed as a side product to a significant extent only by V.
      parvula and Pelobacter propionicus; the latter formed hydrogen preferentially
      when using ethanol as substrate. Acrylyl-CoA reductase of C. homopropionicum and
      Clostridium neopropionicum was found nearly exclusively in the cytoplasm thus
      confirming that this reduction step is unlikely to be involved in energy
      conservation. C. homopropionicum exhibited higher K(S) and higher micro(max)
      values, as well as higher specific substrate turnover rates than P.
      freudenreichii. The results allow us to conclude that C. homopropionicum using
      the acrylyl-CoA pathway with low growth yield obtains its specific competitive
      advantage compared to P. freudenreichii not through higher substrate affinity or
      metabolic shift toward enhanced acetate-plus-hydrogen formation but through
      faster specific substrate turnover.

PMID- 12052553
TI  - Expression of a streptococcal glucosyltransferase as a fusion to a solute-binding
      protein in Lactobacillus fermentum BR11.
AB  - BspA is a non-covalently anchored cystine-binding protein from Lactobacillus
      fermentum BR11. It has previously been used to present antigens derived from
      infectious organisms on the L. fermentum BR11 cell surface. In this study, the
      capacity of BspA to present a very large polypeptide was tested. A temperature
      sensitive plasmid was constructed that encodes a 175-kDa chimeric protein
      consisting of a fusion between BspA and an N-terminally truncated derivative of
      the Streptococcus salivarius ATCC 25975 glucosyltransferase GtfJ. This plasmid
      was introduced into the L. fermentum genome. Integrants were able to incorporate
      20-40 nmol sucrose derived glucose into glucan per ml culture per optical density
      unit. The glucosyltransferase activity was external to the cytoplasmic membrane
      and bound to the cell. Unlike native BspA, the BspA-GtfJ fusion could not be
      removed from the cell by 5 M LiCl wash.

PMID- 12052554
TI  - Characterization of a virulent bacteriophage specific for Escherichia coli
      O157:H7 and analysis of its cellular receptor and two tail fiber genes.
AB  - A virulent phage, named PP01, specific for Escherichia coli O157:H7 was isolated
      from swine stool sample. The phage concentration in a swine stool, estimated by
      plaque assay on E. coli O157:H7 EDL933, was 4.2x10(7) plaque-forming units per g
      sample. PP01 infects strains of E. coli O157:H7 but does not infect E. coli
      strains of other O-serogroups and K-12 strains. Infection of an E. coli O157:H7
      culture with PP01 at a multiplicity of infection of two produced a drastic
      decrease of the optical density at 600 nm due to cell lysis. The further
      incubation of the culture for 7 h produced phage-resistant E. coli O157:H7
      mutant. One PP01-resistant E. coli O157:H7 mutant had lost the major outer
      membrane protein OmpC. Complementation by ompC from a O157:H7 strain but not from
      a K-12 strain resulted in the restoration of PP01 susceptibility suggesting that
      the OmpC protein serves as the PP01 receptor. DNA sequences and homology analysis
      of two tail fiber genes, 37 and 38, responsible for the host cell recognition
      revealed that PP01 is a member of the T-even bacteriophages, especially the T2
      family.

PMID- 12052555
TI  - Purification and partial gene sequence of the tyrosine decarboxylase of
      Lactobacillus brevis IOEB 9809.
AB  - Some lactic acid bacteria contain a tyrosine decarboxylase (TDC) which converts
      tyrosine to tyramine, a biogenic amine frequently encountered in fermented food
      and wine. Purification and microsequencing of the TDC of Lactobacillus brevis
      IOEB 9809 allowed us to determine a partial sequence of the TDC gene encoding 264
      amino acids of the enzyme. Analysis of this protein sequence revealed typical
      features of pyridoxal phosphate-dependent amino acid decarboxylases while not any
      known decarboxylase was closely related to the TDC of L. brevis IOEB 9809. In
      addition, we could detect other L. brevis strains carrying a TDC gene in a rapid
      assay based on the polymerase chain reaction.

PMID- 12052556
TI  - A broad host range plasmid vector that does not encode replication proteins.
AB  - The 640-bp minimal replication region derived from a plasmid DNA preparation from
      an Acidothiobacillus ferrooxidans strain capable of autonomous replication in a
      range of Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa,
      Acinetobacter calcoaceticus and Alcaligenes faecalis) was identified. This DNA
      fragment (named TFK replicon) does not encode Rep proteins and appears to be
      unrelated to other known replicons.

PMID- 12052557
TI  - Comparison of 23S polymerase chain reaction-restriction fragment length
      polymorphism and amplified fragment length polymorphism techniques as typing
      systems for thermophilic campylobacters.
AB  - In this study, we evaluated the combination of polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) and amplified fragment length
      polymorphism (AFLP) molecular typing techniques for the analysis of thermophilic
      campylobacter species isolated from clinical and poultry samples. 23S PCR-RFLP
      analysis performed to fingerprint 69 strains exhibited an excellent level of
      typability. Eleven different types were defined at 100% linkage level following
      numerical analysis of band patterns. Differentiation of Campylobacter jejuni and
      Campylobacter coli at species level was achieved although no significant
      relationship could be observed between the profiles and the origin of the
      strains. Simplified AFLP analysis of the isolates disclosed the presence of 66
      different banding patterns. The resulting dendrogram showed a high diversity
      among the strains studied. All the isolates were grouped within eight main types
      with a 69% homology degree among them. Differentiation at subspecies level was
      possible but no significant relationship could be observed between the AFLP
      profiles and the origin of the strains. When used in combination, 23S PCR-RFLP
      and single-enzyme AFLP methods can be applied to determine taxonomic and
      epidemiological relationships among thermophilic campylobacters.

PMID- 12052558
TI  - A mutation in rpoS enhances biofilm formation in Escherichia coli during
      exponential phase of growth.
AB  - Biofilm formation in Escherichia coli is a process that involves slow growth and
      stress conditions where several molecular signals and growth phase regulated
      genes are involved. Here we show that rpoS mutant strains (defective in the
      stress regulator sigma(S)) exhibit an increased production of biofilm, especially
      in the exponential phase of growth. Our results indicate that rpoS mutants
      produce an extracellular factor that promotes the production of biofilm during
      the exponential phase of growth. Thus, RpoS plays an important role in the
      regulation of the amount and initiation of biofilm formation in E. coli.

PMID- 12052559
TI  - Isolation and characterization of a novel Pseudomonas sp., strain YG1, capable of
      degrading pyrrolidine under denitrifying conditions.
AB  - A denitrifying bacterium, strain YG1, capable of degrading pyrrolidine under
      denitrifying conditions, was isolated. On the basis of phenotypic and
      phylogenetic characteristics, it was identified as a member of the genus
      Pseudomonas. During the anaerobic degradation of pyrrolidine, YG1 reduced a
      stoichiometric amount of nitrate to nitrogen gas, demonstrating that the
      degradation of pyrrolidine is coupled with respiratory nitrate reduction. YG1
      also degraded pyrrolidine with a higher degradation rate under aerobic conditions
      than under denitrifying conditions.

PMID- 12052560
TI  - A molecular approach for early monitoring of decay basidiomycetes in wood chips.
AB  - A DNA-based method for the early detection and identification of decay
      basidiomycetes on wood chips is described. From 26 species of wood-decaying
      basidiomycetes and 20 species of wood-inhabiting ascomycetes, DNA fragments
      containing the internal transcribed spacers, 5.8S and partial 28S rDNA were
      amplified by PCR using the ITS1-F-NL2 rDNA primer pair and analysed through
      sequencing and restriction digestion. A decay basidiomycete-specific restriction
      fragment length polymorphism (RFLP) pattern was generated by DraI. Using this PCR
      RFLP method the detection of decay fungi is possible 4 days after the inoculation
      of the wood chips with either a single culture or mixed species.

PMID- 12052561
TI  - Monoclonal antibody of IgG isotype against a cross-reactive lipopolysaccharide
      epitope of Chlamydia and Salmonella Re chemotype enhances infectivity in L-929
      fibroblast cells.
AB  - A murine monoclonal antibody (MAb) 202D7 of IgG3 isotype recognizes a
      lipopolysaccharide (LPS) epitope of Chlamydia spp. and cross-reacts with the Re
      chemotype LPS of Salmonella and Escherichia coli. The antibody exhibits strong
      complement activating properties and stimulates phagocytosis of Salmonella
      enterica serovar Minnesota Re mutant by murine macrophages. Salmonella Re mutants
      are non-invasive for cell monolayers but still can enter and replicate in L-929
      murine fibroblast cells. The entry of bacteria within the cells increases five
      fold in the presence of MAb 202D7. The antibody mediates attachment and enhances
      five-fold the infectivity of Chlamydia pneumoniae into L-929 cells, which
      suggests a possible IgG-mediated mechanism of entry and survival of the pathogen
      in fibroblast cells.

PMID- 12052562
TI  - Isolation and characterisation of a 13.8-kDa bacteriolytic enzyme from house dust
      mite extracts: homology with prokaryotic proteins suggests that the enzyme could
      be bacterially derived.
AB  - Bacteriolytic activity was detected in extracts of whole mite and spent growth
      medium (SGM) from the clinically important Dermatophagoides pteronyssinus and
      Dermatophagoides farinae mites and was most abundant in whole mite extract. Gram
      positive organisms Micrococcus lysodeikticus, Bacillus megaterium and Listeria
      monocytogenes were preferentially lysed and the lytic activity was enhanced by
      thiols, destroyed by mite proteases, inhibited by HgCl2 and high concentrations
      of NaCl but was resistant to heat and acid treatment. Substrate SDS-PAGE analysis
      indicated the presence of several lytic enzymes, two of which were isolated from
      D. pteronyssinus spent growth medium extract by hydroxyapatite chromatography.
      The N-terminal amino acid sequence of one of them was then used in PCR-based
      cloning studies. The complete amino acid sequence of this protein was determined
      and cDNA found to encode a 130-amino acid residue mature protein with a 20-amino
      acid leader sequence. The deduced protein demonstrated sequence similarity with
      the C-terminal regions of a group of bacterial proteins belonging to the P60
      superfamily. These data suggest that the enzyme is derived from bacteria within
      the mites rather than from mites per se.

PMID- 12052563
TI  - Enhancement of the protective efficacy of an oprF DNA vaccine against Pseudomonas
      aeruginosa.
AB  - The outer membrane protein F gene (oprF) of Pseudomonas aeruginosa was recently
      shown by us to protect mice from P. aeruginosa chronic pulmonary infection when
      used as a DNA vaccine administered by three biolistic (gene gun) intradermal
      inoculations given at 2-week intervals. In the present study, we used two
      different strategies to improve the protective efficacy of the DNA vaccine. In
      the first strategy, mice were primed with two biolistic intradermal inoculations
      with the oprF vaccine and then were given a final intramuscular booster
      immunization containing either a synthetic peptide-keyhole limpet hemocyanin
      (KLH) conjugate or a chimeric influenza virus. Both the synthetic peptide
      conjugate and the chimeric virus contained peptide 10, a previously identified
      immunoprotective epitope of protein F. The second strategy involved the addition
      of a second outer membrane protein to the vaccine. DNA encoding a fusion protein
      comprised of the C-terminal half of protein F fused to OprI was administered by
      three biolistic intradermal inoculations. Challenge with P. aeruginosa in a
      chronic pulmonary infection model demonstrated that boosting with the chimeric
      virus (but not with peptide-KLH) or adding oprI to the DNA vaccine significantly
      enhanced protection as compared to that afforded by the oprF vaccine given alone.
      Thus, both strategies appear to augment the protection afforded by an oprF-only
      DNA vaccine.

PMID- 12052564
TI  - Spore diffusate isolated from some strains of Aspergillus fumigatus inhibits
      phagocytosis by murine alveolar macrophages.
AB  - Aspergillus fumigatus is a ubiquitous fungus that grows in decaying organic
      matter. It can cause disease in both immunodeficient and immunocompetent patients
      by using virulence factors to escape the host defenses. Some of these factors,
      such as a diffusate, released from the spores of A. fumigatus, have previously
      been described. This diffusate was demonstrated to inhibit oxidative burst and
      phagocytosis of coated red blood cells. The present study has shown that this
      substance can inhibit the phagocytosis of A. fumigatus spores by murine alveolar
      macrophages (MALU) and evaluated the action of this substance. We quantified
      phagocytosis by MALU cells with and without diffusate and evaluated the
      inhibition of phagocytosis by testing diffusates from different strains. We
      conclude that the spore diffusate of some strains of A. fumigatus can reversibly
      decrease the ability of alveolar macrophages to ingest A. fumigatus spores.

PMID- 12052565
TI  - Production and characterization of monoclonal immunoglobulin A antibodies
      directed against Salmonella H:g,m flagellar antigen.
AB  - Hybridomas were generated after intragastral immunization of BALB/c mice with
      live Salmonella suberu and subsequent fusion between isolated spleen lymphoblasts
      and myeloma cells. Three monoclonal antibodies (MAbs) of immunoglobulin A (IgA)
      isotype were selected and characterized. All of them were found to recognize the
      H:g epitope in enzyme-linked immunosorbent assay and immunoblotting but did not
      react with all H:g-expressing strains in slide agglutination test. All MAbs
      strongly agglutinated Salmonella enteritidis type strain and a large number of S.
      enteritidis clinical isolates. They were not bactericidal in the presence of
      complement. All hybridoma clones produced secretory IgA forms, which were found
      in the gastrointestinal tract of mice bearing hybridoma as a subcutaneous
      'backpack' tumor or after intravenous application of purified MAbs. The IgA MAbs
      stability demonstrated in different tests together with their antigen specificity
      and strong agglutination ability make them a useful diagnostic tool for
      serotyping of Salmonella strains.

PMID- 12052566
TI  - Identification of a chemotactic, MCP-1-like protein from Mycobacterium avium.
AB  - In the immunocompetent host, Mycobacterium avium is responsible for chronic
      localized pulmonary disease, which is characterized by the presence of increased
      numbers of activated T cells and macrophages in the lungs. M. avium organisms as
      well as sonic extracts of M. avium were found to act as chemoattractants for THP
      1 cells as well as monocytes, monocyte-derived macrophages and alveolar
      macrophages obtained from normal human donors in an in vitro chemotaxis assay,
      where a significantly higher number of cells were found in wells containing M.
      avium compared to control wells. Proteolytic treatment of M. avium sonicate
      resulted in significant loss (50%) of chemotactic activity. Monoclonal antibodies
      against recombinant human monocyte chemoattractant protein-1 (MCP-1) were found
      to cross-react with a 34-kDa protein of M. avium sonicate on Western blot and
      inhibit M. avium sonicate-mediated chemotaxis of THP-1 cells (47%). These data
      suggest the presence of an 'MCP-1 like' molecule on M. avium. Recruitment of host
      immune regulatory cells to the site of infection by pathogens may be involved in
      generating a local immune response or may be a bacterial strategy for survival
      within the host by recruiting the cells that they infect, i.e. macrophages.

PMID- 12052567
TI  - Mycobacterium tuberculosis mammalian cell entry operon (mce) homologs in
      Mycobacterium other than tuberculosis (MOTT).
AB  - The cloned mammalian cell entry gene mce1a from Mycobacterium tuberculosis
      confers to non-pathogenic Escherichia coli the ability to invade and survive
      inside macrophages and HeLa cells. The aim of this work was to search for and
      characterize homologs of the four M. tuberculosis mammalian cell entry operons
      (mce1, mce2, mce3 and mce4) in mycobacteria other than tuberculosis (MOTT). The
      dot-blot and polymerase chain reaction (PCR) experiments performed on 24 clinical
      isolates representing 20 different mycobacterial species indicated that the mce
      operons were widely distributed throughout the genus Mycobacterium. BLAST search
      results showed the presence of mce1, mce2 and mce4 homologs in Mycobacterium
      bovis, Mycobacterium avium and Mycobacterium smegmatis. A homologous region for
      the mce3 operon was also found in M. avium and M. smegmatis. DNA and protein
      alignments were done to compare the M. tuberculosis mce operons and the deduced
      M. bovis, M. avium, and M. smegmatis homologs. The deduced proteins of M. bovis
      mce1, mce2 and mce4 operons had 99.6-100% homology with the respective M.
      tuberculosis mce proteins (MTmce). The similarity between M. avium mce proteins
      and the individual M. tuberculosis homologs ranged from 56.2 to 85.5%. The
      alignment results between M. smegmatis mce proteins and the respective MTmce
      proteins ranged from 58.5% to 68.5%. Primer sets were designed from the M.
      tuberculosis mce4a gene for amplification of 379-bp fragments. Amplification was
      successful in 14 strains representing 11 different mycobacterial species. The PCR
      fragments were sequenced from 10 strains representing eight species. Alignment of
      the sequenced PCR products showed that mce4a homologs are highly conserved in the
      genus Mycobacterium. In conclusions, the four mce operons in different
      mycobacterial species are generally organized in the same manner. The
      phylogenetic tree comparing the different mce operons showed that the mce1 operon
      was closely related to the mce2 operon and mce3 diverged from the other operons.
      The wide distribution of the mce operons in pathogenic and non-pathogenic
      mycobacteria implicates that the presence of these putative virulence genes is
      not an indicator for the pathogenicity of the bacilli. Instead, the pathogenicity
      of these factors might be determined by their expression.

PMID- 12052568
TI  - Proinflammatory cytokine profile in Vibrio vulnificus septicemic patients' sera.
AB  - Vibrio vulnificus causes a fulminant and frequently fatal septicemia in
      susceptible hosts. The present study was designed to evaluate the proinflammatory
      cytokine profile in V. vulnificus septicemia patients' sera and the effect of
      doxycycline therapy on the levels of proinflammatory cytokines. Levels of
      proinflammatory cytokines, tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta and IL-6, were measured in the sera of V. vulnificus septicemic patients
      and normal healthy volunteers using colorimetric sandwich ELISA. The mean values
      of TNF-alpha, IL-1beta and IL-6 in the sera of V. vulnificus patients (n=33)
      increased by 210-, 232- and 40-fold in comparison with those of normal healthy
      volunteers (n=5), but only the IL-6 level showed a statistically significant
      difference (P<0.05) between the two groups. Sera from the cases for which
      doxycycline treatment histories were obvious were designated 'before-treatment'
      (TX). All the others were included in the after-TX group. In the before-TX group
      (n=5), the levels of TNF-alpha and IL-1beta significantly increased (P<0.05) in
      comparison with the after-TX group (n=5). IL-6 levels in the two groups showed no
      difference. In conclusion, the levels of the well known proinflammatory cytokines
      TNF-alpha, IL-1beta and IL-6 increased in the V. vulnificus septicemic patients'
      sera, and the levels of TNF-alpha and IL-1beta decreased significantly after
      doxycycline treatment. These data indicate that proinflammatory cytokines might
      play a critical role in V. vulnificus septicemia like in other endotoxemic
      shocks. The use of doxycycline as an effective bactericidal agent and as an
      effective modulator of proinflammatory cytokines is supported.

PMID- 12052569
TI  - Hantavirus-specific antibodies in rodents and humans living in Kuwait.
AB  - Hantaviruses are found in widely scattered areas of the world and are transmitted
      by inhalation of virus-contaminated aerosols of rodent excreta. The present study
      was undertaken in Kuwait to investigate the serological evidence for hantavirus
      infection in rodents and humans. Sera were collected from 283 wild rodents and
      183 human subjects (46 Kuwaitis and 137 non-Kuwaitis). The rodent sera were
      investigated for the presence of antibodies against the Seoul and Puumala strains
      of the hantaviruses by enzyme-linked immunosorbent assay and immunofluorescence
      technique using the virus-infected Vero E6 cells. The findings showed the
      presence of anti-hantavirus antibodies in seven out of the 283 (2.8%) rodents.
      Antibodies against the Seoul strain were present in six (2.1%) and against the
      Puumala strain in three (1%) rodents. Further, it was observed that three out of
      84 (3.6%) of the Rattus norvegicus and four out of 174 (2.3%) Mus musculus had
      anti-hantavirus antibodies. Two rodents belonging to species Mus musculus had
      antibodies against both strains of the hantaviruses. Out of 183 human sera, 13
      (7%) were positive for hantavirus antibodies. Among the Kuwaitis 5/46 (11%) and
      among the non-Kuwaitis 8/137 (6%) were positive for the hantavirus antibodies.
      Antibodies to both Puumala and Hantaan strains were detected in Kuwaitis as well
      as in non-Kuwaitis. Although no human case of hantavirus illness has yet been
      reported in Kuwait, the serological evidence of infection suggests a constant
      vigil.

PMID- 12052571
TI  - Happy birthday neuroleptics! 50 years later: la folie du doute.
AB  - Given that we are celebrating the 50th birthday of neuroleptics introduction in
      psychiatry, the author proposes to take a look at certain results related to
      therapeutic practice. After a brief chronological literature review of the
      clinical practices and theoretical models that have controlled drug treatment of
      schizophrenia, the author presents a critical review of four meta-analyses. Since
      Delay, Deniker and Harl's initial report, the story of neuroleptics comprises
      several periods. In 1963, the hyper-dopaminergic theory of psychoses was
      proposed. Another period began with models mainly based on the serotonin/dopamine
      relative blockade receptor hypothesis. More recently, a new framework to
      understand the differential effect of antipsychotics is related to the
      appropriate modulation (e.g., fast dissociation) of the D2 receptor alone. The
      concept of atypicality has become a new vista for research and to market new
      compounds. However, after 50 years of neuroleptic drugs, are we able to answer
      the following simple questions: Are neuroleptics effective in treating
      schizophrenia? Is there a difference between atypical and conventional
      neuroleptics? How do the efficacy and safety of newer antipsychotic drugs compare
      with those of clozapine? Actually, the answers yielded by these simple questions
      by meta-analysis should elicit in us a good deal of humility. If we wish to base
      psychiatry on evidence-based medicine, we run a genuine risk in taking a closer
      look at what has long been considered fact. Each psychiatrist must continue to be
      critical, sceptical, optimistic (not overoptimistic) and to learn in order to
      integrate the positive aspects of our growing knowledge base.

PMID- 12052570
TI  - Burkholderia anthina sp. nov. and Burkholderia pyrrocinia, two additional
      Burkholderia cepacia complex bacteria, may confound results of new molecular
      diagnostic tools.
AB  - Nineteen Burkholderia cepacia-like isolates of human and environmental origin
      could not be assigned to one of the seven currently established genomovars using
      recently developed molecular diagnostic tools for B. cepacia complex bacteria.
      Various genotypic and phenotypic characteristics were examined. The results of
      this polyphasic study allowed classification of the 19 isolates as an eighth B.
      cepacia complex genomovar (Burkholderia anthina sp. nov.) and to design tools for
      its identification in the diagnostic laboratory. In addition, new and published
      data for Burkholderia pyrrocinia indicated that this soil bacterium is also a
      member of the B. cepacia complex. This highlights another potential source for
      diagnostic problems with B. cepacia-like bacteria.

PMID- 12052572
TI  - Fringe phenotypes in autism: a review of clinical, biochemical and cognitive
      studies.
AB  - Progress in identifying the genetic vulnerability factors in autism requires
      correct identification of the inherited phenotype(s). This can be achieved not
      only by the accurate description of the affected subject but also by the
      identification of vulnerability traits in non-affected relatives of autistic
      probands. This review will focus on this last strategy and principally on
      clinical, biochemical and cognitive traits.

PMID- 12052573
TI  - Tardive dyskinesias and antipsychotics: a review.
AB  - Currently, tardive dyskinesia (TD) remains an important clinical problem. The
      average prevalence is estimated at 30%. The appearance of antipsychotics has
      opened new paths. The extrapyramidal profile of these molecules is more favorable
      than that of conventional neuroleptics. In order to assess their prophylactic as
      well as curative potential, we reviewed the literature concerning four of these
      atypical antipsychotics: clozapine, risperidone olanzapine and amisulpride.
      Clozapine seems to induce fewer cases of TD than the conventional neuroleptics,
      and has a specific therapeutic effect. However, the risk of agranulocytosis
      reduces the possibility of utilisation. Risperidone appears to be an effective
      therapy, but several authors report cases of TD during treatment. Furthermore,
      larger studies and longer follow-ups are necessary to confirm the efficiency of
      olanzapine and amisulpride. Further studies and observations are still necessary
      before drawing any conclusion for these new atypical antipsychotic actions. They
      are doubtlessly promising, but we cannot ignore the notion of risk-benefit;
      regular monitoring and listening to the subjective experience of the patients
      must remain uppermost in the choice of therapy.

PMID- 12052574
TI  - Patients' and relatives' satisfaction with psychiatric services in a large
      catchment area in Rome.
AB  - OBJECTIVE: To assess the satisfaction of patients and their relatives with
      psychiatric care and to identify variables associated with any dissatisfaction.
      METHODS: The study was performed in a defined psychiatric catchment area in south
      Rome, Italy. All eligible patients and relatives who had contacts with services
      during a predefined period were asked to participate. Satisfaction with
      psychiatric services was measured with a previously validated questionnaire.
      RESULTS: A total of 890 patients were asked to participate in the study and 855
      (96%) accepted. Also, 270 relatives were asked to participate and 265 (98%)
      agreed. The satisfaction with services expressed by outpatients and their
      relatives was fairly good, with the exception of poor satisfaction with
      information about treatment and involvement in the treatment programme. The
      satisfaction of inpatients and their relatives was significantly lower, with the
      issue of information-giving by staff appearing particularly critical. Among
      patients, variables associated with dissatisfaction were being an inpatient,
      having a diagnosis of psychosis, being in contact with services for more than 6
      years, and being single. Among relatives, being female and being the relative of
      an inpatient were associated with dissatisfaction. For both patients and
      relatives, receiving inpatient care was the strongest predictor of
      dissatisfaction. CONCLUSIONS: The results suggest that inpatient care, especially
      for psychotic patients, needs to be improved and that special attention should be
      devoted to inform adequately and to engage in treatment both patients and their
      relatives. Lack of information appears to be a crucial determinant of
      dissatisfaction with psychiatric care among both patients and their relatives.

PMID- 12052575
TI  - Predictors of noncompliance in males with first-episode schizophrenia,
      schizophreniform and schizoaffective disorder.
AB  - PURPOSE: Many factors influencing compliance in schizophrenia have been reported
      in the literature. Our aim was to assess predictors of noncompliance in male
      patients with first-episode schizophrenia, schizophreniform and schizoaffective
      disorder in a naturalistic setting. SUBJECTS AND METHODS: Fifty-six male
      patients, discharged from hospital, were included in a 1-year follow-up study.
      Psychopathological symptoms were assessed with positive and negative syndrome
      scale at admission and discharge, while extrapyramidal side effects were recorded
      weekly during hospitalisation using the Simpson-Angus and Barnes akathisia
      scales. Socio-demographic and some other variables were also recorded. RESULTS:
      Thirty patients (53.6%) dropped out of treatment in the first year and 21 of them
      relapsed. With the Cox survival analysis three predictors of noncompliance were
      found: diagnosis of schizophrenia versus the other two diagnoses, positive
      symptoms at admission, and lack of insight at discharge. Discussion. In spite of
      a specific methodology and selection of only first-episode male patients, the
      results are in accordance with the findings of other authors. This confirms the
      universality of noncompliance in psychotic patients. CONCLUSIONS: First-episode
      patients have a high dropout rate. However, in compliant patients, the relapse
      rate was low, and therefore special attention and compliance-promoting
      interventions in first-episode patients are needed.

PMID- 12052576
TI  - Cognitive patterns in subtypes of schizophrenia.
AB  - AIM: Because of the heterogeneity of schizophrenia, this study researched
      different cognitive patterns in distinct subtypes of schizophrenic patients.
      METHODS: Thirty-five Diagnostic and Statistical Manual IV (DSM IV) schizophrenic
      patients and 35 healthy controls were included. Patients were categorized into
      deficit, disorganized and positive subtypes with the schedule for the deficit
      syndrome (SDS) and the positive and negative syndrome scale (PANSS).
      Executive/attentional functions were assessed with the modified card sorting test
      (MCST), a test of verbal fluency, the trail making test (TMT) and the Stroop
      color-word test (Stroop test). Episodic memory was explored through the
      California verbal learning test (CVLT). RESULTS: The positive subtype had some
      executive/attentional (fluency and Stroop tests) and mnesic performances in the
      normal range, suggesting the preservation of good cognitive skills. In contrast,
      the deficit and disorganized subtypes had major mnesic and executive/attentional
      dysfunctions compared to healthy subjects. The deficit subtype compared to the
      control group performed predominantly worse on the MCST and fluency, whereas the
      disorganized subtype had the lowest scores on the TMT and the Stroop test.
      CONCLUSION: This study showed distinct cognitive patterns in deficit,
      disorganized and positive patients in comparison with the controls, suggesting a
      heterogeneous cognitive dysfunction in schizophrenia.

PMID- 12052577
TI  - New aspects in the treatment of heroin dependence with special reference to
      neurobiological aspects.
AB  - The Swiss trials on medical prescription of injectable diacetylmorphine
      (pharmaceutical heroin) for "severe" heroin dependence provoked very
      controversial commentaries. Despite methodological shortcomings, the evaluation
      of the Swiss heroin trials yielded some interesting findings. Study participants
      showed substantial improvements in health and well-being and noticeable declines
      in illicit drug use and criminal activities. Heroin prescription may thus be
      helpful for some of those who continue to regularly use illicit heroin while
      maintained on methadone or who refuse other available treatment options. However,
      research-based evidence suggests that the intravenous (IV) application of heroin
      under medical supervision may have untoward side effects. Recent studies have
      shown that heroin injections produce transient, but significant decreases in
      systemic and cortical oxygenation most likely secondary to respiratory
      depression. Among others, these effects are the subject of ongoing studies.

PMID- 12052578
TI  - Modafinil monotherapy in depression.

PMID- 12052579
TI  - Switching to amisulpride due to hepatic complications.

PMID- 12052580
TI  - Upper-extremity self-amputation in a case with schizophrenia.

PMID- 12052581
TI  - Putting elective cesarean into perspective.

PMID- 12052582
TI  - Endometrial ablation.

PMID- 12052583
TI  - Emergency peripartum hysterectomy: experience at a community teaching hospital.
AB  - OBJECTIVES: To estimate the incidence, indications, risk factors, and
      complications associated with emergency peripartum hysterectomy at a community
      based academic medical center. METHODS: We analyzed retrospectively 47 of 48
      cases of emergency peripartum hysterectomy performed at Winthrop-University
      Hospital from 1991 to 1997. Emergency peripartum hysterectomy was defined as one
      performed for hemorrhage unresponsive to other treatment less than 24 hours after
      delivery. Fisher exact test, Wilcoxon rank sum test, and Cochran-Armitage exact
      trend test were used for analysis. RESULTS: There were 48 emergency peripartum
      hysterectomies among 34,241 deliveries for a rate of 1.4 per 1000. Most frequent
      indications were placenta accreta (48.9%, 12 with previa, 11 without previa),
      uterine atony (29.8%), previa without accreta (8.5%), and uterine laceration
      (4.3%). Placenta accreta was the most common indication in multiparous women
      (58.8%, 20 of 34), uterine atony the most common in primiparas (69.2%, nine of
      13). Twenty-two of 23 (95.6%) women with placenta accreta had a previous cesarean
      delivery or curettage. The number of cesarean deliveries or curettages increased
      the risk of placenta accreta proportionally. Thirty-eight (80.9%) of the
      hysterectomies were subtotal. Postoperative febrile morbidity was 34%; other
      morbidity was 26.3%. CONCLUSION: Placenta accreta has become the most common
      indication for emergency peripartum hysterectomy.

PMID- 12052584
TI  - The likelihood of placenta previa with greater number of cesarean deliveries and
      higher parity.
AB  - OBJECTIVE: To examine the relationship between prior cesarean delivery and
      placenta previa. METHODS: A hospital-based, case-control study was conducted in
      which 316 multiparous women with placenta previa were identified. Controls
      consisted of 2051 multiparous women with spontaneous vaginal deliveries.
      Information on prior cesarean delivery was examined in three forms: as a
      dichotomous variable, as an ordinal variable, and as a set of three indicator
      variables for one, two, and three or more cesarean deliveries. Multivariable
      logistic regression modeling was used to obtain an adjusted estimate of this
      association. RESULTS: Women with a prior cesarean delivery were more likely to
      have a placenta previa than those without (odds ratio [OR] 1.59, 95% confidence
      interval [CI] 1.21, 2.08). The likelihood of placenta previa increased as both
      parity and number of cesarean deliveries increased. Thus, the adjusted OR for a
      primiparous woman with one cesarean delivery was 1.28 (95% CI 0.82, 1.99). For a
      woman who has four or more deliveries with only a single cesarean delivery, the
      OR increases to 1.72 (95% CI 1.12, 2.64). This trend continues with greater
      parity and a greater number of cesarean deliveries such that the likelihood of
      placenta previa for a woman with parity greater than four and greater than four
      cesarean deliveries was OR 8.76 (95% CI 1.58, 48.53). CONCLUSION: This study
      supports the association between prior cesarean delivery and placenta previa and
      demonstrates that the joint effect of parity and prior cesarean delivery is
      greater than that of either variable alone.

PMID- 12052585
TI  - Failure of methotrexate and internal iliac balloon catheterization to manage
      placenta percreta.
AB  - BACKGROUND: Placenta percreta is a rare but potentially lethal condition.
      Previously described conservative measures to avoid life-threatening hemorrhage
      and preserve fertility include use of methotrexate and uterine artery
      embolization. CASE: A woman with suspected placenta percreta diagnosed on
      ultrasound in the second trimester was delivered by classic, fundal cesarean at
      30 weeks' gestation for bleeding and premature rupture of membranes. The placenta
      was left in situ, and she was treated with methotrexate. Postpartum bleeding 1
      week later was managed by internal iliac balloon catheterization and manual
      transcervical removal of the placenta, which resulted in hysterectomy and
      required massive blood transfusion. CONCLUSION: Placenta percreta managed
      conservatively with methotrexate and internal iliac balloon catheterization
      resulted in serious morbidity.

PMID- 12052586
TI  - Microwave endometrial ablation versus endometrial resection: a randomized
      controlled trial.
AB  - OBJECTIVE: To compare menstrual status, satisfaction, and acceptability of
      microwave endometrial ablation with transcervical endometrial resection for the
      treatment of heavy menstrual bleeding. METHODS: Women were randomized to either
      endometrial ablative method. Menstrual status, satisfaction, acceptability, and
      changes in health-related quality of life were obtained by a self-completed
      questionnaire. Case note review and personal communication identified further
      surgery rates at 2 years after each procedure. RESULTS: Among the original 263
      women who underwent endometrial ablation, 249 (95%) returned questionnaires at 2
      years. Menstrual status in both groups was similar, although the amenorrhea rate
      was higher after microwave endometrial ablation. Seventy-nine percent of women
      were either completely or generally satisfied after microwave ablation compared
      with 67% after transcervical endometrial resection. Health-related quality-of
      life scores remained higher than at recruitment for both treatments. Hysterectomy
      rates were similar at 2 years (11.6% after microwave endometrial ablation and
      12.7% after transcervical endometrial resection), and no repeat endometrial
      ablative procedures were required. CONCLUSION: Microwave endometrial ablation is
      an effective alternative to transcervical endometrial resection for dysfunctional
      uterine bleeding.

PMID- 12052587
TI  - Five-year follow-up of endometrial ablation: endometrial coagulation versus
      endometrial resection.
AB  - OBJECTIVE: A randomized, controlled trial was performed to compare the patient
      complication rate, effectiveness, and satisfaction rate of transcervical
      hysteroscopic endometrial coagulation versus endometrial resection in the
      treatment for heavy dysfunctional bleeding. METHODS: One hundred and twenty women
      requiring endometrial ablation for the treatment of heavy bleeding disorders
      entered the study. All patients were offered a clinical examination 24 months
      postoperatively and had a questionnaire by mail 5 years after the initial
      treatment. The number of complications during and after the operation, re
      ablations, and hysterectomies were registered. A bleeding index and the patient
      satisfaction rate were stated. RESULTS: Sixty-one patients were treated by
      endometrial coagulation, and 59 were treated by endometrial resection. No
      differences between the two groups were observed concerning fluid absorption,
      bleeding, perforation, and infection. At the 5-year follow-up, 64% of the
      patients had only one ablation, 15% were treated twice, 15% had a hysterectomy,
      and 6% were lost to follow-up. After 5 years, the bleeding index was halved in
      patients with menses. Seventy-nine percent of the women would recommend the
      treatment to their best female friend. CONCLUSION: We found no significant
      differences in the frequency of complications. Only 15% of the women had a
      hysterectomy after 5 years. No significant difference was observed with respect
      to bleeding reduction and patient satisfaction in the two groups.

PMID- 12052588
TI  - Second-trimester genetic sonography in patients with advanced maternal age and
      normal triple screen.
AB  - OBJECTIVE: To estimate the value of second-trimester genetic sonography in
      detecting fetal Down syndrome in patients with advanced maternal age (at least 35
      years) and normal triple screen. METHODS: Since July 1999, a prospective
      collection and recording of all individual triple screen risks for fetal Down
      syndrome was initiated for all patients with advanced maternal age presenting in
      our ultrasound unit for second-trimester genetic sonography. Genetic sonography
      evaluated the presence or absence of multiple aneuploidy markers. Outcome
      information included the results of genetic amniocentesis, if performed, and the
      results of pediatric assessment and follow-up after birth. RESULTS: By June 2001,
      959 patients with advanced maternal age and normal triple screen were identified.
      Outcome information was obtained in 768 patients. The median risk for fetal Down
      syndrome based on maternal age was 1:213 (range 1:37-1:274). The median risk for
      fetal Down syndrome based on triple screen results was 1:1069 (range 1:275
      1:40,000). A total of 673 patients had normal genetic sonography, and none (0%)
      had Down syndrome; 95 had one or more aneuploidy markers present, and four (4.2%)
      had fetuses with Down syndrome. The triple screen risks for these four fetuses
      ranged from 1:319 to 1:833. CONCLUSION: This study suggests that patients with
      advanced maternal age and normal genetic sonography carried very little risk for
      Down syndrome. The use of genetic sonography may increase the detection rate of
      fetal Down syndrome in this group of pregnant women.

PMID- 12052589
TI  - Bleeding after loop electrosurgical excision procedure performed in either the
      follicular or luteal phase of the menstrual cycle: a randomized trial.
AB  - OBJECTIVE: To estimate the perioperative or postoperative bleeding rates after
      treatment of cervical intraepithelial neoplasia by loop electrosurgical excision
      procedure in either the follicular or luteal phase of the menstrual cycle.
      METHODS: A randomized controlled trial was carried out to compare the outcomes in
      terms of primary and secondary hemorrhage between patients treated by loop
      electrosurgical excision procedure during either the follicular (30 women) or
      luteal phase (30 women) of the menstrual cycle. The two groups did not differ in
      terms of mean age, grade of cervical intraepithelial neoplasia, depth of
      excision, parity, and duration of menses. Primary outcome measures included the
      objective and subjective assessment of intraoperative and postoperative bleeding.
      RESULTS: Women treated during the luteal phase of the menstrual cycle experienced
      significantly more postoperative bleeding than women treated during the
      follicular phase, as assessed by the fall in hematocrit levels (P <.001) and
      subjective reports. Intraoperative bleeding was judged to be more severe in women
      treated during the luteal phase of the cycle by a single, blinded colposcopist (P
      =.02). These women also experienced higher levels of anxiety postoperatively,
      which resulted in more consultations with medical staff (P =.007). CONCLUSION:
      The use of loop electrosurgical excision procedure to treat cervical
      intraepithelial neoplasia results in less bleeding if performed during the
      follicular phase of the menstrual cycle.

PMID- 12052590
TI  - Evaluation of outpatient hysteroscopy and ultrasonography in the diagnosis of
      endometrial disease.
AB  - OBJECTIVE: To develop a multivariable approach to determine the added value of
      tests in routine practice where some diagnostic information is already available
      from clinical history. METHODS: Multivariable logistic regression models were
      built in a stepwise fashion, considering the clinical sequence used in the rapid
      access ambulatory diagnosis clinic (clinical history followed by transvaginal
      ultrasonography and hysteroscopy). The reference standard for confirmation of
      diagnosis was endometrial biopsy. The diagnostic accuracy of the models was
      determined by the area under the receiver operating characteristic curve.
      RESULTS: The area under the receiver operating characteristic curve for the model
      including historical features alone was 0.78. When hysteroscopy and
      ultrasonography were each added to the model, it increased to 0.81 (P =.008 for
      improvement) and 0.82 (P =.02 for improvement), respectively. CONCLUSION: The
      type of stepwise analysis we have developed is crucial in facilitating meaningful
      clinical interpretation about the value of diagnostic technology. Our finding
      that hysteroscopy or ultrasonography marginally but significantly increased the
      prediction of serious endometrial pathology above that predicted from patient
      history alone needs validation in an independent data set. The use of this
      approach is recommended when evaluating strategies for diagnosis.

PMID- 12052591
TI  - Secondary cytoreductive surgery for recurrent epithelial ovarian cancer.
AB  - OBJECTIVE: To review our experience with secondary cytoreductive surgery for
      recurrent epithelial ovarian cancer with regard to its feasibility, morbidity,
      mortality, patient selection, and survival. METHODS: Forty-six patients who
      underwent secondary cytoreductive surgery at the Royal Hospital for Women,
      Sydney, between July 1988 and October 1996 were retrospectively reviewed. The
      mean age at surgery was 50.3 years, and the median disease-free interval was 26
      months. Eighty-nine percent of patients had a disease-free interval of at least
      12 months. Twenty-five patients (54%) had localized disease at the time of
      surgery. Univariate survival outcomes were analyzed using the log rank test, and
      survival curves were calculated using the method of Kaplan-Meier. RESULTS: Two
      patients (4%) were inoperable and 19 patients (41%) were cytoreduced to no
      macroscopic disease. There was one postoperative death (2%), and four patients
      (8.7%) had significant postoperative morbidity. With a median follow-up of 88
      months, the overall median survival was 22.5 months. Patients with a disease-free
      interval of less than 12 months after their initial treatment had a median
      survival of 6 months, compared with 11 months if the disease-free interval was 12
      24 months and 39 months for those with a disease-free interval of 24 months or
      more (P =.001, log rank). Patients who had any residual disease had a median
      survival of 11 months, whereas those with no residual disease had a median
      survival of 38 months (P =.002, log rank). CONCLUSION: For carefully selected
      patients with recurrent epithelial ovarian cancer: 1) complete surgical resection
      is feasible more commonly than with primary cytoreduction, 2) serious morbidity
      and mortality are acceptable, and 3) significant survival benefit accrues when a)
      all macroscopic disease can be resected, or b) the disease-free interval is 24
      months or more.

PMID- 12052592
TI  - Severity of premenstrual symptoms in a health maintenance organization
      population.
AB  - OBJECTIVE: To describe severity of emotional and physical symptoms in a large
      diverse sample; to examine demographic, health status, and behavioral correlates
      of symptom severity; and to describe use of medications and alternative remedies
      for premenstrual symptoms. METHODS: A total of 1194 women, ages 21-45, selected
      from members of a large northern California health maintenance organization,
      completed daily ratings of symptom severity for two menstrual cycles. An
      empirically derived algorithm defined symptom severity groups as minimal (n =
      186), moderate (n = 801), severe (n = 151), or premenstrual dysphoric disorder (n
      = 56). Symptom severity as a continuous variable was defined by the two-cycle
      mean symptom ratings in the luteal phase. Demographic, health status, and
      behavioral factors and use of treatments for premenstrual symptoms were assessed
      by self-report. RESULTS: Luteal phase symptom-specific ratings were generally
      significantly greater in the premenstrual dysphoric disorder group than in the
      other groups (P <.001). Symptom severity score increased with each comorbidity
      and decreased with each year of age. Symptom severity was also inversely
      associated with oral contraceptive use (emotional symptoms) and better perceived
      health (physical symptoms). Hispanics reported greater severity of symptoms, and
      Asians less, relative to whites. Use of herbal and nutritional supplements for
      premenstrual symptoms steadily increased from 10.8% in the minimal group to 30.4%
      in the premenstrual dysphoric disorder group (P <.01). CONCLUSION: The degree of
      premenstrual symptom severity varies in the population, is relatively constant
      within each woman over two consecutive cycles, particularly for emotional
      symptoms, and is influenced by age, race/ethnicity, and health status.

PMID- 12052593
TI  - Extremely preterm vaginal breech delivery en caul.
AB  - OBJECTIVE: To describe an alternative method of vaginal birth to the conventional
      assisted delivery for extremely preterm breech infants within intact amnions, and
      to compare the immediate neonatal outcomes with those delivered by cesarean.
      METHODS: Retrospective review of singleton breech deliveries under 26 weeks'
      gestation after spontaneous labor with intact membranes. Nine "en caul" vaginal
      births after tocolysis and six cesarean deliveries performed for the sole
      indication of preterm labor were identified between 1996 and 2001. RESULTS: The
      vaginal group's mean gestation and cervical dilatation on admission were 23(+6)
      weeks and 3.2 cm, respectively, and 24(+6) weeks and 2.8 cm in the cesarean
      group. Vaginal delivery occurred an average of 4 days after admission and 1 day
      for cesarean delivery. Mean time interval between the first corticosteroid
      injection and delivery was greater in the vaginal group (90 versus 22 hours).
      Failure to start or complete a steroid course was more likely in the operative
      group (67% versus 11%). Mean birth weights were comparable. Five-minute Apgar
      scores and cord pHs were 6 and 7.41, respectively, for vaginal births, and 5.5
      and 7.32 after cesarean deliveries. Fifty-five percent of vaginally delivered
      infants had a 5-minute Apgar score less than 7, with 22% of the whole group dying
      during the first week of life. This compared with 66% and 50%, respectively, for
      cesarean infants. Of the survivors, average age at discharge was 121 days for
      both groups. CONCLUSION: Vaginal birth can be effected in extremely preterm
      breech pregnancies with intact membranes by adopting the "en caul" delivery
      method.

PMID- 12052594
TI  - Do women prefer female obstetricians?
AB  - OBJECTIVE: To investigate gender preferences for obstetricians in a hospital
      setting and to examine its relationship to patient satisfaction. METHODS: Using
      methods of qualitative analysis, we interviewed a convenience sample of 67
      obstetric patients during their postpartum hospital stay, asking open-ended
      questions about gender preferences of health care providers and satisfaction with
      health care. RESULTS: Overall, 58% of patients (n = 39) had no preference for
      physician gender, 34% (n = 23) preferred female physicians, and 7% (n = 5)
      preferred male physicians. Physicians' interpersonal style, communication style,
      and technical expertise were considered important characteristics by patients.
      Although most patients had no preference for physician gender, the majority of
      patients preferred a female nurse. Patient satisfaction scores were not
      associated with physician gender. CONCLUSION: Our study found that a majority of
      women did not prefer a female obstetrician. Our results suggest that physician
      gender is less important to patients than other physician characteristics.

PMID- 12052595
TI  - Perianal versus anorectal specimens: is there a difference in Group B
      streptococcal detection?
AB  - OBJECTIVE: To investigate whether specimens obtained from the perianal area have
      a Group B streptococcal culture detection rate similar to anorectal specimens.
      METHODS: This is a prospective cohort study at a tertiary care university
      affiliated teaching hospital. A total of 136 pregnant women between 33 and 40
      weeks' gestation were recruited. Three samples for Group B streptococcal culture
      detection were obtained from each subject in the following order: perianal
      sample, vaginoperianal sample, and an anorectal sample. The women were asked to
      rank their pain or discomfort with obtaining the anorectal sample. The
      vaginoperianal specimen is the standard sample obtained from antepartum patients
      in this clinic, and, therefore, it serves as the control. RESULTS: Of the 136
      subjects, 26.5% of the control, vaginoperianal samples were positive for Group B
      streptococcal culture. In comparison, 27.2% of the anorectal specimens and 28.7%
      of the perianal specimens were positive for Group B streptococcal culture. There
      was no statistically significant difference in the detection of Group B
      streptococcal culture among the three sample sites. Evaluation of the pain
      experienced with an anorectal sampling showed that 68% of subjects ranked their
      pain between mild to moderate, and 5% noted severe pain. CONCLUSION: The Group B
      streptococcal detection rate was not different among the three sampling sites.
      Therefore, pregnant women do not need to be subjected to the additional pain of
      anorectal sampling to detect Group B Streptococcus.

PMID- 12052596
TI  - The relationship between maternal serum thyroid-stimulating immunoglobulin and
      fetal and neonatal thyrotoxicosis.
AB  - OBJECTIVE: To estimate whether the risk of neonatal thyrotoxicosis was related to
      the value of maternal thyroid-stimulating immunoglobulin in women with Graves
      disease. METHODS: The records of pregnant women undergoing testing for thyroid
      stimulating immunoglobulin over a 10-year period were analyzed. Neonatal
      thyrotoxicosis was defined as the presence of tachycardia, goiter, hydrops,
      tremulousness, voracious appetite, irritability, cardiomegaly, or congestive
      heart failure, with elevated thyroid hormone levels. The relationship between
      maternal thyroid-stimulating immunoglobulin values and the development of
      thyrotoxicosis was examined. The sensitivity, specificity, and positive and
      negative predictive values were calculated using an arbitrarily chosen cutoff for
      thyroid-stimulating immunoglobulin. RESULTS: Twenty-nine women with a history of
      Graves disease and positive thyroid-stimulating immunoglobulin values were
      available for analysis. Of the 35 live births, there were six cases of neonatal
      thyrotoxicosis (17.1%). A maternal thyroid-stimulating immunoglobulin value at
      least 5 index units predicted neonatal thyrotoxicosis with a sensitivity of 100%,
      specificity of 76.0%, positive predictive value of 40.0%, and negative predictive
      value of 100%. CONCLUSION: Pregnancies complicated by high values of maternal
      thyroid-stimulating immunoglobulin appear to be at risk of developing neonatal
      thyrotoxicosis.

PMID- 12052597
TI  - Oral versus vaginal misoprostol for labor induction.
AB  - OBJECTIVE: To compare the safety and effectiveness of vaginal with oral
      misoprostol for induction of labor. METHODS: A total of 107 women with clinical
      indication for induction were randomly assigned to receive oral or vaginal
      misoprostol. Doses of 100 microg of oral or 25 microg of vaginal misoprostol were
      given every 3-4 hours. If cervical ripening or active labor did not occur,
      repeated doses of oral (100-200 microg) or vaginal (25-50 microg) were given
      until labor was established. RESULTS: Fifty-nine women received oral misoprostol,
      and 48 received vaginal administration. Delivery time was similar for the vaginal
      and oral arms (1074 +/- 488 minutes versus 930 +/- 454 minutes, P =.11). Parity
      was significantly different (P =.04) for the vaginal and oral groups. The
      cesarean delivery rate was similar for the vaginal and oral arms (17% versus 15%,
      P =.72). The number of medication administrations was consistent between groups.
      Birth weight was not different for patients in the control and treatment groups
      (vaginal 3281 +/- 507 g versus oral 3359 +/- 541 g, P =.44). Chorioamnionitis and
      tachysystole were comparable for the oral and vaginal groups. There was no
      statistical difference in neonatal outcomes. Similar proportions of infants were
      admitted to the well baby nursery and intermediate care nursery. CONCLUSION:
      These findings indicate that, in a closely supervised hospital setting with
      adequate monitoring, oral misoprostol has the potential to induce labor as safely
      and effectively as its vaginal analogue.

PMID- 12052598
TI  - Risk of hepatitis B transmission in breast-fed infants of chronic hepatitis B
      carriers.
AB  - OBJECTIVE: To measure the rate of hepatitis B (HBV) transmission from chronic HBV
      carriers to breast-fed infants after immunoprophylaxis. METHODS: Since 1992,
      information on women with HBV during pregnancy has been collected in a
      prospective longitudinal study. Those HBV carriers and their infants
      participating in a county HBV immunoprophylaxis program were identified. Infants
      were followed for up to 15 months and examined for hepatitis B infection by
      hepatitis B surface antigen (HBsAg). RESULTS: A total of 369 infants born to
      women with chronic HBV met the inclusion criteria and received hepatitis B immune
      globulin at birth and the full course of the hepatitis B vaccine series. We
      compared 101 breast-fed infants with 268 formula-fed infants. There was no
      significant difference between the two groups with respect to the number of women
      who were positive for hepatitis B e antigen (HBeAg) (22% versus 26%, P =.51).
      Three women in the breast-feeding group had liver transaminase abnormalities,
      compared with six women in the formula-feeding group (P =.29). Overall, there
      were nine cases of HBV infection transmission (2.4%). None of the 101 breast-fed
      infants and nine formula-fed infants (3%) were positive for HBsAg after the
      initial vaccination series (P =.063). The mean length of time for breast-feeding
      was 4.9 months (range 2 weeks to 1 year). CONCLUSION: With appropriate
      immunoprophylaxis, including hepatitis B immune globulin and hepatitis B vaccine,
      breast-feeding of infants of chronic HBV carriers poses no additional risk for
      the transmission of the hepatitis B virus.

PMID- 12052600
TI  - Prognostic factors for the success of thermal balloon ablation in the treatment
      of menorrhagia.
AB  - OBJECTIVE: To identify predictive factors that will ensure successful menorrhagia
      treatment using hot fluid balloon endometrial ablation. METHODS: This is a
      prospective study on patients referred for menorrhagia and treated with hot fluid
      thermal balloon ablation. Potential prognostic factors for assessing the success
      of treatment were recorded. Success was defined as patient satisfaction and no
      subsequent hysterectomy at 2-year follow-up. RESULTS: A total of 130 women were
      included in the final analysis. The cumulative rate of patients undergoing a
      hysterectomy after 2 years was 12%. After 2 years, 81% of the remaining patients
      were satisfied with the results of the treatment. Predictive factors for adverse
      outcome were a retroverted uterus (hazard rate ratio 3.3, 95% confidence interval
      [CI] 1.2, 8.6), pretreatment endometrial thickness of at least 4 mm (hazard rate
      ratio 3.6, 95% CI 1.3, 11), and the duration of menstruation (hazard rate ratio
      1.2, 95% CI 1.0, 1.3, per day in excess of 9 days). The risk of an adverse
      outcome declined steadily with increasing age (hazard rate ratio 0.86, 95% CI
      0.77, 0.96 per year over 42 years of age). Uterine depth and dysmenorrhea were
      not predictive factors, which significantly affected outcome. CONCLUSION: Young
      age, retroverted uterus, endometrial thickness of at least 4 mm, and prolonged
      duration of menstruation were associated with an increased risk of treatment
      failure. Uterine depth and dysmenorrhea had limited impact on the effectiveness
      of balloon ablation.

PMID- 12052599
TI  - Liquid-based Papanicolaou smears without a transformation zone component: should
      clinicians worry?
AB  - OBJECTIVE: To evaluate whether ThinPrep smears without versus those with a
      transformation zone component were more likely to have falsely negative cytology
      findings. METHODS: Women aged 18-50 (N = 4389) attended one of three Planned
      Parenthood clinics between 1997 and 2001 for screening by ThinPrep Papanicolaou
      and polymerase chain reaction-based human papillomavirus (HPV) DNA testing. Women
      with 1) any cytologic abnormality, 2) high-risk HPV types, and 3) a random sample
      with normal Papanicolaou and negative HPV tests were offered repeat cytology,
      colposcopy, and biopsy. Cytology and biopsy diagnoses at the colposcopy visit
      were reviewed according to the presence (n = 3689) or absence (n = 700) of a
      transformation zone component at screening. RESULTS: Among women with normal
      cytology at screening, histologic detection of at least cervical intraepithelial
      neoplasia grade 2 (odds ratio 1.3, 95% confidence interval 0.5, 3.3) at
      colposcopy did not differ significantly between transformation zone-positive and
      zone-negative smears. Histologically confirmed cervical intraepithelial neoplasia
      grade 1 was detected more often among smears lacking a transformation zone
      component (odds ratio 2.0, confidence interval 1.0, 3.8). Transformation zone
      negative smears were more common among older women, current oral contraceptive
      users, those past the 14th day of their last menstrual period, and those negative
      for high-risk HPV types. CONCLUSION: Absence of a transformation zone component
      in a screening ThinPrep Papanicolaou test was not associated with missed high
      grade lesions. Based upon our data, we do not recommend repeat screening of
      reproductive-aged women with negative liquid-based tests and no cytologic
      evidence of a transformation zone component.

PMID- 12052601
TI  - Recognition of occult bladder injury during the tension-free vaginal tape
      procedure.
AB  - OBJECTIVE: To identify signs and the etiology of occult bladder injury during the
      tension-free vaginal tape sling procedure. METHOD: The charts of 140 women who
      underwent a tension-free vaginal tape procedure were reviewed, and complications
      were tabulated and analyzed. The tension-free vaginal tape procedure was
      performed in six fresh-frozen pelves to demonstrate the mechanism of the occult
      bladder injury. RESULTS: Occult bladder injury was suspected when cystoscopy
      instillation fluid flowed from the plastic sheath that covers the prolene tape
      after the extraction of the tension-free vaginal tape trocar. Three of six cases
      of intraoperative bladder injury had occult bladder injury identified on repeat
      cystoscopic inspection. The bladder injury caused by the rough edge at the point
      of attachment of the tension-free vaginal tape to the trocar was reproducible in
      three of 12 tension-free vaginal tape applications in fresh-frozen pelves.
      Traction on the tension-free vaginal tape reapproximates the injured bladder
      edges and potentially promotes spontaneous healing. CONCLUSION: Bladder injuries
      may go unrecognized during a tension-free vaginal tape procedure. Continuous
      seepage of water through the prolene plastic sleeve is suggestive of occult
      bladder injury and requires repeat cystoscopy to identify the potential site of
      injury.

PMID- 12052602
TI  - A comparison of women's regret after vasectomy versus tubal sterilization.
AB  - OBJECTIVE: To compare the 5-year cumulative probability of regret and risk
      factors for regret among women whose husbands underwent vasectomy with women
      after tubal sterilization. METHODS: A total of 525 women whose husbands underwent
      vasectomy were compared with 3672 women who underwent tubal sterilization in a
      prospective, multicenter, cohort study. RESULTS: The cumulative probability of a
      woman expressing regret within 5 years after her husband's vasectomy was 6.1%
      (95% confidence interval [CI] 3.6, 8.6), which was similar to the 5-year
      cumulative probability of regret among women after tubal sterilization (7.0%, 95%
      CI 5.8, 8.1). Women who reported substantial conflict with their husbands before
      vasectomy were more than 25 times more likely to request that their husband have
      a reversal than women who did not report such conflict (rate ratio 25.3, 95% CI
      2.9, 217.2). Similarly, women who reported substantial conflict with their
      husbands or partners before tubal sterilization were more then three times as
      likely to regret their decision and more than five times as likely to request a
      reversal than women who did not report such conflict (rate ratio 3.1, 95% CI 1.4,
      7.0, and rate ratio 5.4, 95% CI 1.6, 17.6, respectively). CONCLUSION: Most women
      did not express regret after their husband's vasectomy and the probability of
      regret was similar to sterilized women. However, when there was substantial
      conflict between a woman and her husband before vasectomy or tubal sterilization,
      the probability of subsequent request for reversal was increased.

PMID- 12052604
TI  - The methylenetetrahydrofolate reductase 677 C-->T polymorphism and preeclampsia
      in two populations.
AB  - OBJECTIVE: The C677T polymorphism of the 5,10 methylenetetrahydrofolate reductase
      (MTHFR) gene is associated with decreased MTHFR activity and elevated plasma
      homocysteine levels with the result of an increased risk for vascular disease.
      Because thrombosis of the maternal spiral arteries can be one of the causative
      events in the disease, it has been suggested that the C677T polymorphism may also
      play a role in the pathogenesis of preeclampsia. Our case-control study
      investigated the prevalence of the 677T allele in two ethnically different
      populations and the potential association of the 677T allele with preeclampsia.
      Special attention was paid to the potential contribution of the fetal genotype to
      disease risk. METHODS: Blood samples were collected from 81 mothers and 61
      newborns after preeclampsia and 99 mothers and 61 newborns with normal
      pregnancies. Genomic DNA was amplified by polymerase chain reaction with locus
      specific primers, and presence of the polymorphism was determined by enzymatic
      digestion with HinfI and visualization on polyacrylamide gels. RESULTS: Genotypes
      carrying the MTHFR 677T allele were significantly more frequent in German
      Croatians than in Indonesians in both patients and controls (P =.0033 in
      controls). In contrast, the prevalence of genotypes with the 677T allele was not
      increased among patients with preeclampsia compared with controls in both ethnic
      groups (P >.5 in all groups). In Germans, the frequency of 677T homozygotes among
      controls even exceeded that observed in preeclamptic patients (677T/T genotype
      frequency 0.20 in controls and 0.07 in patients). We did not find an increased
      prevalence of paternally inherited 677T alleles in preeclamptic fetuses relative
      to controls or other signs of maternal-fetal transmission distortion. CONCLUSION:
      In our study, the MTHFR C677T polymorphism was not associated with an increased
      risk for preeclampsia on the level of the maternal or fetal genotype. However,
      significant differences of the frequency of genotypes carrying the 677T allele
      between Middle-Europeans and Indonesians were identified.

PMID- 12052603
TI  - The effect of tablet moistening on labor induction with intravaginal misoprostol:
      a randomized trial.
AB  - OBJECTIVE: To estimate whether a dosage of 50 microg of misoprostol tablets
      moistened with 3% acetic acid and administered intravaginally is more efficacious
      for labor induction than a similar dosage regimen using dry tablets. METHODS: A
      total of 177 women who presented with an indication for cervical ripening and
      labor induction were randomly assigned to one of two treatment groups: 1)
      intravaginal misoprostol in dry tablet form, or 2) intravaginal misoprostol
      moistened with 1 mL of 3% acetic acid solution. The primary outcome assessed was
      the interval from start of induction to vaginal delivery. To detect at least a
      3.5-hour difference in the primary outcome with 80% power, 87 subjects were
      required in each group. RESULTS: Among 162 patients evaluated, 80 were allocated
      to the misoprostol dry group and 82 to the misoprostol moistened group. No
      significant difference was noted for the mean +/- standard deviation interval to
      vaginal delivery: 1130 +/- 636 minutes for the group who received dry tablets and
      1004 +/- 636 minutes for those who received moistened misoprostol tablets (P
      =.25). Additionally, no statistically significant differences were noted between
      the groups with respect to need for oxytocin, proportion of patients delivered
      after a single dose, intrapartum complications (including tachysystole and
      uterine hyperstimulation), mode of delivery, or perinatal outcomes. CONCLUSION:
      Tablet moistening with 3% acetic acid solution does not seem to improve the
      efficacy of intravaginally administered misoprostol for labor induction.

PMID- 12052605
TI  - Ontogenetic localization and distribution of S-100beta protein in human placental
      tissues.
AB  - OBJECTIVE: To investigate whether S-100beta, a brain-specific protein found in
      amniotic fluid and fetal circulation, is present in fetoplacental tissues
      throughout gestation. METHODS: S-100beta protein localization and concentration
      were assessed in placentae, fetal membranes, and cord vessels. Tissues were
      obtained from 40 pregnant women at different gestational ages: first trimester (n
      = 10), second trimester (n = 10), early third trimester (n = 10), and late third
      trimester (n = 10). RESULTS: In the placenta, S-100beta was localized in villous
      and intermediate trophoblast cells. The intensity of immunostaining and protein
      concentration increased with advancing gestation. S-100beta protein was also
      present in amnion, trophoblast, and decidual cells of fetal membranes, and in
      endothelial cells of umbilical vessels at all gestational ages. CONCLUSION: This
      study demonstrated that fetoplacental tissues contain S-100beta protein,
      suggesting that these tissues may, at least in part, be responsible for the high
      level found in the fetal circulation. Although the significance of placental S
      100beta is unknown, this origin should be taken into account when this protein is
      used as a marker of brain injury in the fetus or infant at birth.

PMID- 12052606
TI  - Contraception for women in selected circumstances.
AB  - OBJECTIVE: To review new evidence regarding ten controversial issues in the use
      of contraceptive methods among women with special conditions and to present World
      Health Organization recommendations derived in part from this evidence. DATA
      SOURCES: We searched MEDLINE and PREMEDLINE databases for English-language
      articles, published between January 1995 and December 2001, for evidence relevant
      to ten key contraceptive method and condition combinations: combined oral
      contraceptive (OC) use among women with hypertension or headaches, combined OC
      use for emergency contraception and adverse events, progestogen-only
      contraception use among young women and among breast-feeding women, tubal
      sterilization among young women, hormonal contraception and intrauterine device
      use among women who are human immunodeficiency virus (HIV) positive, have AIDS,
      or are at high risk of HIV infection. Search terms included: "contraception,"
      "contraceptives, oral," "progestational hormones," "medroxyprogesterone-17
      acetate," "norethindrone," "levonorgestrel," "Norplant," "contraceptives,
      postcoital," "sterilization, tubal," "intrauterine devices," "hypertension,"
      "stroke," "myocardial infarction," "thrombosis," "headache," "migraine," "adverse
      effects," "bone mineral density," "breast-feeding," "lactation," "age factors,"
      "regret," and "HIV." STUDY SELECTION: From 205 articles, we identified 33 studies
      published in peer-reviewed journals that specifically examined risks of
      contraceptive use among women with pre-existing conditions. TABULATION,
      INTEGRATION, AND RESULTS: Combined OC users with hypertension appear to be at
      increased risk of myocardial infarction and stroke relative to users without
      hypertension. Combined OC users with migraine appear to be at increased risk of
      stroke relative to nonusers with migraine. The evidence for the other eight
      method and condition combinations was either insufficient to draw conclusions or
      identified no excess risk. CONCLUSION: Of ten contraceptive method and condition
      combinations assessed, the evidence supported an increased risk of cardiovascular
      complications with combined OC use by women with hypertension or migraine. As new
      evidence becomes available, assessment of risk and recommendations for use of
      contraceptive methods can be revised accordingly.

PMID- 12052607
TI  - Vaginal breech delivery is no longer justified.

PMID- 12052608
TI  - Vaginal breech delivery is still justified.

PMID- 12052609
TI  - Summary of the updated recommendations from the Public Health Service Task Force
      to reduce perinatal human immunodeficiency virus-1 transmission in the United
      States.
AB  - Within the last decade, substantial advances have been made in the treatment of
      human immunodeficiency virus (HIV)-infected pregnant women and in the prevention
      of perinatal HIV-1 transmission, and recommendations for care continually change.
      Within this rapidly evolving field, the Public Health Service Task Force
      Perinatal HIV Guidelines Working Group, which is composed of pediatric and
      obstetric experts in HIV infection, community representatives, and federal agency
      representatives, currently meets by monthly conference calls to review new data
      related to prevention of mother-to-child HIV transmission and management of women
      with HIV infection. This group periodically issues updates to their guidelines,
      "Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs
      in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce
      Perinatal HIV-1 Transmission in the United States," which are available on the
      HIV/AIDS Treatment Information Service Web site (http://www.hivatis.org).

PMID- 12052610
TI  - Professionalism in medicine: an A-Z primer.
AB  - To be successful as physicians, we should adhere to a simple, time-honored code
      of conduct. We must commit ourselves to a lifetime of self-directed learning. We
      must strive to be thoughtful, kind, and sensitive. We must avoid arrogance,
      dogmatism, and negativism. We must be honest, moral, tolerant, trustworthy, and
      above all else, humble and compassionate. Consistent adherence to these traits
      will help us maintain the nobility and credibility of the medical profession.

PMID- 12052611
TI  - Sonographic definition of the fetal situs.
AB  - The sonographic definition of the fetal situs is of diagnostic importance.
      However, the current methods that rely on the position of both heart and stomach
      are not always reliable. Presented are the right-hand rule for transabdominal
      scanning and the left-hand rule for transvaginal scanning which enable the
      definition of the fetal situs. The presented rules of thumb enable a definite
      diagnosis of the fetal situs in all cases and apply for all fetal positions and
      presentations.

PMID- 12052612
TI  - Mode of term singleton breech delivery.

PMID- 12052614
TI  - Placenta accreta.

PMID- 12052616
TI  - Obstetrician-gynecologists and the intrauterine device: a survey of attitudes and
      practice.

PMID- 12052618
TI  - Furthering the profession: the early years of the American Gynecological Club and
      its first European tours.

PMID- 12052622
TI  - Detection of Chlamydia trachomatis infection with DNA extracted from formalin
      fixed paraffin-embedded tissues.
AB  - It is a well-known fact that tubal stenosis and/or peritubal adhesion are often
      associated with Chlamydia trachomatis infection. Although tubal pregnancy may be
      attributed to this infection, there are only extremely rare cases in which the
      presence of C. trachomatis has been confirmed by immumo-histochemical examination
      on tissues isolated from patients with tubal pregnancy. We thus tried to confirm
      the presence of C. trachomatis infection by detecting DNA of the organism in
      tissues surgically isolated from patients with tubal pregnancy. Two detection
      methods, a ligase chain reaction (LCR) method and an immuno-histochemical
      staining which detects an antigen of C. trachomatis, were compared using paraffin
      embedded tissue samples which were surgically isolated from patients with tubal
      pregnancy or hydrosalpinx. The LCR method was capable of detecting DNA of C.
      trachomatis in tissue samples in which the C. trachomatis-specific antigen could
      not be detected using immuno-histochemical staining. This was due to the fact
      that immuno-histochemical staining methods are applicable to the analysis of
      sequences the length of which range from 200 to 400 bp (base pairs), while the
      LCR method used here allows the analysis of sequences as small as 48 bp. This
      fact makes the LCR method a very convenient tool, as compared with immuno
      histochemical methods, for analysis of the paraffin embedded tissue samples where
      by effects of formalin--used for fixation for pathologic diagnosis--the risk of
      fragmenting the DNA samples is relatively high. Presence of C. trachomatis DNA as
      detected by LCR method in surgically isolated samples from patients with tubal
      pregnancy supports the involvement of Chlamydia trachomatis infection in the
      occurrence of tubal pregnancy. Accordingly the LCR method is capable of detecting
      DNA of C. trachomatis in paraffin-embedded samples of tubal tissue in which
      presence of C. trachomatis could not be confirmed by an immuno-histochemical
      staining method.

PMID- 12052623
TI  - Detection of EspB using reversed passive latex agglutination: application to
      determination of enteropathogenic Escherichia coli.
AB  - We developed a new practical method to identify enteropathogenic Escherichia coli
      (EPEC) by detecting the pathogenic factor, EspB. E. coli were cultured in
      Dulbecco's Modification of Eagle's Medium (DMEM), and EspB was detected in the
      culture supernatant by reversed passive latex agglutination (RPLA). All 63 E.
      coli strains harboring the eaeA gene encoding intimin were positive for RPLA, and
      all 25 strains without the eaeA gene were negative. Among these 63 eaeA-positive
      strains, 38 Shiga toxin-producing E. coli (STEC) produced Shiga toxin (Stx) under
      the same culture conditions (DMEM). Subtypes of EspB alpha, beta and gamma were
      antigenically cross-reactive to each other as determined by RPLA and Western
      blotting. A kit for Stx detection (RPLA) is commercially available and therefore
      this RPLA for detection of EspB could be a practical method to define EPEC in
      both clinical laboratories and the field.

PMID- 12052624
TI  - Antifungal activities of fluconazole, caspofungin (MK0991), and anidulafungin (LY
      303366) alone and in combination against Candida spp. and Crytococcus neoformans
      via time-kill methods.
AB  - The activities of the echinocandins caspofungin and anidulafungin were evaluated
      alone and in combination with fluconazole using time-kill methods against
      isolates of Candida albicans, Candida glabrata, Candida tropicalis, Candida
      krusei, and Cryptococcus neoformans. Antifungal concentrations tested against
      each isolate were 0.5 microg/mL and 20 microg/mL of fluconazole and 0.007
      microg/mL and 2 microg/mL of both caspofungin and anidulafungin. In addition, 20
      microg/mL of fluconazole was tested with 2 microg/mL of caspofungin and
      anidulafungin to test for additive or antagonistic activity. Finally 0.5
      microg/mL of fluconazole was tested with 0.007 microg/mL of caspofungin and
      anidulafungin to test for synergy. Combinations of fluconazole and caspofungin or
      anidulafungin resulted in indifference. Azole-echinocandin combinations do not
      produce antagonistic effects; therefore, combinations of these agents may warrant
      future clinical evaluation.

PMID- 12052625
TI  - Diversity of commensal yeasts within and among healthy hosts.
AB  - We sampled commensal yeasts from three body sites of 24 healthy individuals to
      examine the patterns of commensal yeast species distribution and strain
      relatedness within and among individuals. To examine the short-term dynamics,
      each individual was sampled three times every 35-40 days at each of three body
      sites: mouth, fingernail, and toenail. The hosts included six genealogically
      unrelated individuals and 18 that belonged to four families. A total of 63
      morphologically distinct colonies were isolated, identified, and genotyped. Nine
      yeast species were recovered, including 28 isolates of Candida albicans; 26 of C.
      parapsilosis; 2 each of C. krusei and C. tropicalis; and 1 each of C. famata, C.
      glabrata, C. guilliermondii, C. lusitaniae and Trichosporon beigelii. A
      significant difference in total yeast recovery rate between families was
      observed. However, body sites did not differ in the rates of yeast recovery. The
      three body sites showed different species distributions with the fingernail
      sample containing the highest species diversity, followed by the toenail sample.
      The oral sample contained the lowest species diversity with all 23 oral isolates
      being C. albicans. Among the 63 strains, forty-six unique genotypes were
      identified by PCR fingerprinting. Eleven shared-genotypes were identified, seven
      of which were from the same body site of the same host. The other four were from
      different members of the same family. Several family-specific genotypes and
      genotype clusters were found but the results were inconsistent with strict
      familial transmission of human commensal yeasts. A single host can have multiple
      species or multiple genotypes of the same species at the same or different body
      sites. Changes of species and genotypes over the sampling period for the same
      body site of individual hosts were also observed, including one direct
      observation of familial yeast transmission between two members of the same family
      during our sampling period. Our results indicate dynamic processes of yeast
      colonization, maintenance and evolution in healthy human hosts.

PMID- 12052626
TI  - Diagnosis of histoplasmosis by antigen detection based upon experience at the
      histoplasmosis reference laboratory.
AB  - Histoplasmosis is a common infection in endemic regions of North and Latin
      America, causing a broad spectrum of clinical findings. The diagnosis may be
      missed or delayed because histoplasmosis is not considered in the differential. A
      battery of serologic and mycologic tests may be used for the diagnosis, but each
      has advantages and limitations. Antigen detection may be particularly helpful for
      making a rapid diagnosis in patients with more extensive infection. The purpose
      of this review is to provide a comprehensive discussion of the role of antigen
      detection in the diagnosis of histoplasmosis, to provide the clinician and
      laboratory worker with a fuller understanding of the benefits and limitations of
      this useful laboratory method. This report is based soley upon the experience at
      the Histoplasmosis Reference Laboratory, and can not be used in interpretation of
      results of Histoplasma antigen testing done at other laboratories.

PMID- 12052627
TI  - Use of a nested polymerase chain reaction (N-PCR) to detect Trypanosoma cruzi in
      blood samples from chronic chagasic patients and patients with doubtful
      serologies.
AB  - Chagas disease, caused by Trypanosoma cruzi, is an important endemic illness in
      Latin America. Serologic tests for T. cruzi detection in blood are sensitive, but
      their specificity is unsatisfactory. Direct detection of parasites in blood,
      either by xenodiagnosis or hemoculture, is highly specific but of low
      sensitivity. Molecular assays such as the Polymerase chain reaction (PCR), which
      amplifies certain repetitive sequences of nuclear DNA has been used as a good
      alternative tool for T. cruzi detection in human blood. The present study aimed
      to test PCR diagnosis in chagasic chronic patients and doubtful serologic
      patients attended in GEDOCH (Chagas Disease Study Group/UNICAMP, Brazil). A 149
      bp fragment originated from nuclear DNA was specifically detected in chronic
      chagasic patients. The results of these tests were compared with serologic
      diagnosis performed using standard techniques and xenodiagnosis. We found that 43
      out of 50 patients previously serodiagnosed as chagasic were positive using the N
      PCR method. Thirteen of 30 patients with doubtful serologic results were
      confirmed as positive by N-PCR. Our results suggest that the N-PCR may be a
      complementary tool to serology in the diagnosis of Chagas disease, and that it is
      usefull for parasite detection in patients with chronic disease and patients with
      doubtful serologic results.

PMID- 12052628
TI  - Agar diffusion, agar dilution, Etest, and agar screening test in the detection of
      methicillin resistance in staphylococci.
AB  - Methicillin resistant Staphylococcus is an important worldwide problem.
      Resistance is verified in strains harboring the mecA gene and laboratory methods
      used to detect resistance are object of constant investigation. In the present
      study, 99 clinical isolates of staphylococci (41 S. aureus, 33 S. epidermidis, 12
      S. saprophyticus and 13 members of other species) were submitted to different
      phenotypic methods and conditions. Detection of the mecA gene by PCR was used as
      the reference method and detected 14/41, 10/33, and 10/25 isolates of S. aureus,
      S. epidermidis and other species, respectively. Results showed that, for S.
      aureus and S. epidermidis, agar diffusion, agar dilution, and the E test
      incubated during 24h at 35 degrees C correctly discriminated mecA positive from
      mecA negative isolates. For other species, all methods and conditions presented
      low specificity (ranging from 20% to 66.7%) and, particularly S. saprophyticus,
      may need molecular methods to correctly assess methicillin resistance.

PMID- 12052629
TI  - Potency and antimicrobial spectrum update for piperacillin/tazobactam (2000):
      emphasis on its activity against resistant organism populations and generally
      untested species causing community-acquired respiratory tract infections.
AB  - The in vitro activity of piperacillin/tazobactam and several comparison broad
      spectrum compounds was assessed against recent clinical isolates of Gram-positive
      and -negative bacteria from geographically diverse medical centers in Europe,
      North and Latin America participating in various surveillance programs in 2000.
      Several organisms were characterized for phenotypic expression of various
      resistant determinants such as extended-spectrum beta-lactamase (ESBL) or amp C
      cephalosporinase hyperproduction, and vancomycin resistance in enterococci (VRE).
      Piperacillin/tazobactam retained activity (MIC50) against oxacillin-susceptible
      Staphylococcus spp. (0.12-0.5 microg/ml), Bacillus spp. (0.5 microg/ml),
      vancomycin-susceptible enterococci (>4 microg/ml), and Corynebacterium spp. (2
      microg/ml; not including C. jeikeium) with susceptibility rates of 100.0, 91.7,
      85.7 and 81.8%, respectively. Piperacillin/tazobactam inhibited all Streptococcus
      spp. strains at < or = 16 microg/ml, including penicillin-resistant strains many
      of which were co-resistant to erythromycin (90%) and other beta-lactams. A
      specific breakpoint for these streptococci when testing piperacillin/tazobactam
      appears needed to prevent false-resistant reports using penicillin as a class
      representative. The carbapenems among beta-lactams were the most active agents
      against the ESBL-producing species of Escherichia coli and Klebsiella pneumoniae
      and those strains which hyper-express amp C enzymes including Citrobacter spp.
      and Enterobacter spp. Piperacillin/tazobactam only exhibited modest activity
      against the "amp C resistance group" strains (68.8% susceptible or intermediate,
      MIC < or = 64 microg/ml). Piperacillin/tazobactam (MIC50, 8 microg/ml; 79.5%
      susceptible) was the most active agent tested against multi-drug resistant
      isolates of Pseudomonas aeruginosa. Against sampled Haemophilus influenzae (39.2%
      ampicillin-resistant), piperacillin/tazobactam (MIC(90,) < or = 0.06 microg/ml),
      ceftriaxone and ceftazidime inhibited 100.0% of the isolates at < or = 0.25
      microg/ml. These in vitro surveillance results from the year 2000 on three
      continents, demonstrated a sustained potent activity of piperacillin/tazobactam
      against selected problematic nosocomial and community-acquired pathogens. The
      potential importance of these findings is that this beta-lactamase inhibitor
      combination can be used an empiric treatment of serious infections in hospital
      environments where resistance has emerged, as well as covering nearly all
      isolates of fastidious respiratory tract pathogens acquired in the community
      setting.

PMID- 12052630
TI  - Use of surrogate antimicrobial agents to predict susceptibility to ertapenem.
AB  - Broth or agar dilution susceptibility test results for Enterobacteriaceae (11,775
      strains), anaerobes (2888 strains), staphylococci (2206 strains), Haemophilus
      spp. (840 strains), group A streptococci (280 strains), group B streptococci (269
      strains), Streptococcus pneumoniae (709 strains), and 160 other streptococci were
      analyzed to identify surrogate antimicrobial agents to predict susceptibility to
      ertapenem. Ertapenem MIC interpretive categories approved by the United States
      FDA were compared to those of imipenem, oxacillin (staphylococci), or penicillin
      (streptococci). Ertapenem resistance was rare (1.2%) among 8187 consecutively
      collected clinical isolates of Enterobacteriaceae, including a large proportion
      of isolates from intensive care units. Absolute categorical agreement between
      ertapenem and imipenem, and very major (false susceptible) and major errors
      (false resistant) using imipenem to predict ertapenem results were 97.2%, 0.9%,
      and 0.4%, respectively, for Enterobacteriaceae (10,992 strains tested against
      both drugs) and 99.0%, 0.2%, and 0% for anaerobes. All Haemophilus spp., groups A
      and B streptococci, penicillin-susceptible and -intermediate S. pneumoniae, and
      other penicillin-susceptible streptococci were susceptible to ertapenem. All
      oxacillin-susceptible Staphylococcus aureus were ertapenem susceptible, except 1
      that was intermediate. Surrogate antimicrobial agents that can be used to
      reliably predict ertapenem susceptibility by MIC tests are imipenem for
      Enterobacteriaceae and anaerobes, oxacillin for staphylococci, and penicillin for
      streptococci.

PMID- 12052631
TI  - Spectrum and potency evaluation of a new oxazolidinone, linezolid: report from
      the SENTRY Antimicrobial Surveillance Program, 1998-2000.
AB  - Resistance (R) among Gram-positive cocci has escalated in the last two decades to
      levels necessitating the development and use in the newer drug classes,
      oxazolidinones (linezolid) and streptogramins (quinupristin/dalfopristin [Q/D]).
      The SENTRY Antimicrobial Surveillance Program has monitored these classes before,
      during and after their release by various regulatory agencies. Over 30,000 Gram
      positive strains were tested against >30 drugs by reference broth microdilution
      methods between 1998-2000 in four geographic regions (Asia-Western Pacific
      [APAC], Europe [EU], Latin America [LA], North America [NA]). The tested strains
      were 23,188 staphylococci; 5,103 enterococci and 2,045 streptococci. Among
      staphylococci, linezolid was active against all isolates (MICs, < or =4
      microg/ml) regardless of susceptibility patterns of other antimicrobial agents.
      Similar results were noted for vancomycin (includes one VISA from Hong Kong),
      teicoplanin, and Q/D (<1% R). Gatifloxacin had the widest spectrum among
      fluoroquinolones (FQ) against Staphylococcus aureus (1.5-9.2% R) and coagulase
      negative staphylococci (0.8-4.0%). Linezolid was also active against all
      enterococci (MIC50 and (90,) 2 microg/ml). Q/D was active against only 75.3% of
      vancomycin-resistant enterococci (VRE). The VRE rate was highest in NA (12.4%) >
      EU (3.2%) > LA (1.6%) > APAC (1.3%). Among streptococci, linezolid was
      consistently active (MIC(90,) 1 microg/ml) as were the glycopeptides and Q/D.
      Variable penicillin-R (MIC, > or = 2 microg/ml) was observed among regions: EU
      (32.5%) > APAC (15.1%) > LA (13.8%) > NA (9.6%), and macrolide-R was higher in EU
      (40.3%). Ciprofloxacin-R at > or =4 microg/ml in streptococcal strains was noted
      world wide highest in viridans group streptococci (18.4-25.6%). Linezolid
      remained active (MIC, < or =4 microg/ml) against all Gram-positive species
      strains tested in the SENTRY Program (1998-2000). Q/D, glycopeptides and newer FQ
      compounds were generally less effective in vitro. It remains a prudent practice
      to continue surveillance programs to detect emerging resistance patterns and
      recognize significant regional variations in the oxazolidinone susceptibilities.

PMID- 12052632
TI  - A multicenter evaluation of linezolid antimicrobial activity in North America.
AB  - Overall, 141 centers in North America enrolled in this international surveillance
      study designed to evaluate the in vitro antimicrobial activity and spectrum of
      linezolid, a new oxazolidinone. Each participant tested the susceptibility of
      clinical isolates of staphylococcal species (n = 85) against 12 drugs, and
      enterococcal species (n = 40) against 6 drugs using reference broth microdilution
      trays; and of streptococcal species (n = 25) against 6 drugs using Etests (AB
      BIODISK, Solna, Sweden). Quality control testing was conducted using recommended
      strains, and verification of resistance to linezolid and select other agents was
      performed by a regional monitor. Of the 20,161 isolates collected from sites
      across the United States (US; n = 132) and Canada (n = 9), 18,307 were included
      in this analysis. Oxacillin resistance occurred in 38.7 and 70.6% of
      Staphylococcus aureus and coagulase-negative staphylococcal (CoNS) isolates,
      respectively. Vancomycin resistance was reported in 65.9 and 2.6% of Enterococcus
      faecium and E. faecalis, respectively. Penicillin resistance occurred in 37.2% of
      Streptococcus pneumoniae, 17.5% constituting high-level resistance (MIC, > or =2
      microg/ml). The MIC(90) for linezolid was 1 microg/ml for streptococci, 2
      microg/ml for enterococci and CoNS isolates, and 4 microg/ml for S. aureus. Using
      the US FDA-recommended susceptible breakpoints for linezolid, there were no
      confirmed reports of linezolid resistance (i.e., MIC > or =8 microg/ml). The
      occurrence of linezolid MICs was unimodal and generally varied between, 1-4
      microg/ml for staphylococci (94% of recorded results), 1-2 microg/ml for
      enterococci (93%), and 0.5-1 microg/ml for streptococci (85%). Susceptibility to
      linezolid was not influenced by susceptibility to other antiicrobials such as
      vancomycin, beta-lactams or macrolides. Only linezolid was universally active
      against essentially all tested Gram-positive specimens. The unimodal
      susceptibility pattern is indicative of excellent and near complete activity
      against key Gram-positive pathogens including multiply resistant strains, but
      surveillance for emerging resistances (rare) and the performance of routine
      susceptibility tests to guide patient therapy seems prudent.

PMID- 12052633
TI  - Hypertonic sabouraud broth as a simple and powerful test for Candida dubliniensis
      screening.
AB  - We developed a new screening test for C. dubliniensis based on its inability to
      grow on Sabouraud dextrose broth with 6.5% NaCl. A total of 266 clinical yeast
      isolates and 3 reference strains were tested, including 250 C. albicans and 19 C.
      dubliniensis strains. All C. albicans isolates tested exhibited significant
      growth on hypertonic Sabouraud broth up to 96 h, while, all C. dubliniensis
      isolates did not exhibit any visually detectable growth during the same period.

PMID- 12052635
TI  - New horizons in toxicology for a safer future. Proceedings of EUROTOX 2001. The
      XXXIX European Congress of Toxicology. September 13-16, 2001. Istanbul, Turkey.

PMID- 12052634
TI  - AZD2563, a new oxazolidinone: bactericidal activity and synergy studies combined
      with gentamicin or vancomycin against staphylococci and streptococcal strains.
AB  - AZD2563, a novel oxazolidinone, was tested against 10 well characterized multiple
      resistant strains of staphylococci and viridans group or beta-hemolytic
      streptococci using kill curve kinetic methods. Generally, AZD2563 demonstrated
      bacteriostatic action and modest concentration-dependent cidal activity against a
      minority of strains of both genera. When combined with gentamicin (MIC/4
      concentration), rapid bactericidal action was observed against all streptococci
      tested, but not against the staphylococci. No enhanced activity was noted when
      AZD2563 was added to subinhibitory concentrations of vancomycin. Linezolid used
      as a control, showed the same characteristics, confirming that AZD2563 possesses
      activity comparable to other agents in the oxazolidinone class. AZD2563 remained
      active (MIC, < or = 1 microg/ml) against all 10 strains tested.

PMID- 12052636
TI  - The Gerhard Zbinden memorial lecture: application of biochemical and genetic
      approaches to understanding pathways of chemical toxicity.
AB  - All cells have evolved a complex number of pathways, which allow them to survive
      in a chemically hostile environment. In multicellular organisms, these pathways
      are catalysed by a number of key enzymes, which inhibit the absorption of toxins
      or facilitate their elimination so that they do not accumulate to toxic levels
      within the cell. These cytoprotective pathways are also critical determinants of
      the effectiveness of drug therapy and are thought to have evolved from a limited
      number of biochemical pathways, such as those which allow cells to utilise
      molecular oxygen in respiration without suffering deleterious effects. The study
      of both simple and multicellular organisms has shown that many stress response
      pathways previously considered as distinct adaptive mechanisms in mammalian
      systems are interrelated coordinated responses to toxic challenge. Understanding
      the functions and mechanisms of regulation of the genes involved in these
      pathways has many applications in medical science-in evaluating the role of
      environmental factors in the pathogenesis of human disease, in chemoprevention,
      in drug development and in the application of drug therapy. The use of genetic
      approaches, coupled with new chip-based profiling technologies, will play a key
      role in the development of studies in this research area.

PMID- 12052637
TI  - Update of survey, regulation and toxic effects of mycotoxins in Europe.
AB  - The most frequent toxigenic fungi in Europe are Aspergillus, Penicillium and
      Fusarium species. They produce aflatoxin B1 transformed into aflatoxin M1 found
      in the milk, as well as Ochratoxins and Zearalenone, Fumonisin B1, T-2 toxin, HT
      2 toxin and deoxynivalenol (vomitoxin), which are of increasing concern in human
      health. These mycotoxins are under continuous survey in Europe, but the
      regulatory aspects still need to be set up and/or harmonised at European level.
      They are found in foodstuffs and are not destroyed by normal industrial
      processing or cooking since they are heat-stable. Some of their metabolites are
      still toxic and may be involved in human diseases. Their toxic effects (liver,
      kidney and hematopoetic toxicity, immune toxicity, reproduction toxicity, foetal
      toxicity and teratogenicity, and mainly carcinogenicity) are mostly known in
      experimental models, the extrapolation to humans being always inaccurate. The
      inaccuracy of extrapolation to humans may be explained by the lack of adequate
      food consumption data, lack of knowledge about relative health risks associated
      with specifically proposed limits and by the possibility of synergism with other
      mycotoxins present in the same food commodities. Other pathological causes are
      viral hepatitis, immune or hormonal deficiencies or organ dysfunction. Even when
      a specific biomarker of a given mycotoxin is identified in humans, it remains
      difficult to establish the relation with a given illness, because of genetic
      polymorphism and the possible beneficial influence of diet, and because other
      environmental toxicants may well interfere. The acceptable daily intake limits
      are mostly based on animal data and may be too high, due to the differences in
      the sensitivity of different animal species. The prevention involves first
      reduction of mycotoxin levels in foodstuffs and further increasing the intake of
      diet components such as vitamins, antioxidants and substances known to prevent
      carcinogenesis.

PMID- 12052638
TI  - Food contamination by metals and pesticides in the European Union. Should we
      worry?
AB  - The estimation of the risk associated with dietary intakes of heavy metals and
      pesticide residues by the consumer is a vital and integral part of regulatory
      processes. The exposure of the consumer is compared directly to the acceptable
      daily intake (ADI) for pesticides and to the tolerable daily intake (TDI) for
      heavy metals. The exposure is obtained using the basic equation: Exposure (mg/kg
      b.w./day)=Consumption (mg/kg b.w./day) x Residue (mg/kg). The establishment of
      the ADI and the TDI is based on the results of toxicological studies that involve
      the determination of the lowest-no-observed-adverse-effect level/10 (SF1) x10
      (SF2), where SF corresponds to 'Safety Factor'. SF1 and SF2 account for
      interspecies and intraspecies variability, respectively. In order to evaluate the
      risk for the consumer, that is associated to the presence of heavy metals and
      pesticides in food, a review of the level of contamination in European countries
      has been made. The exposure of European consumers to lead, cadmium, arsenic and
      mercury is superior to the TDI. For pesticides, the first step is to compare the
      detected amount of residues of a specific pesticide to the maximum residue level
      (MRL) authorized in foodstuffs. If the residue level in food exceeds the MRL, the
      theoretical maximum daily intakes and the ADI have to be taken into account in
      order to assess the risk for the consumer.

PMID- 12052639
TI  - Threshold of toxicological concern (TTC) in food safety assessment.
AB  - The threshold of toxicological concern (TTC) is a principle which refers to the
      possibility of establishing a human exposure threshold value for all chemicals,
      below which there is no appreciable risk to human health. The concept that
      exposure thresholds can be identified for individual chemicals in the diet is
      already widely embodied in practice of many regulatory bodies in setting
      acceptable daily intakes (ADIs) for chemicals whose toxicological profile is
      known. However, the TTC concept goes further than this in proposing that a de
      minimis value can be identified for many chemicals, including those of unknown
      toxicity, taking the chemical structure into consideration. This concept forms
      the scientific basis of the US Food and Drug Administration (FDA) '1995 Threshold
      of Regulation' for indirect food additives. The TTC principle has also been
      adopted by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in its
      evaluations of flavouring substances. The establishment of a more widely accepted
      TTC would benefit consumers, industry and regulators. In precluding extensive
      toxicity testing and safety evaluations when human intakes are below such a
      threshold, TTC would focus limited resources of time, cost, animal use and
      expertise on the testing and evaluation of substances with greater potential to
      pose risks to human health and contribute to a reduction in the use of animals.
      An International Life Sciences Institute (ILSI)-Europe expert group has examined
      this TTC principle, which was based on general toxicity endpoints (including
      carcinogenicity), for its applicability in food safety evaluation. In addition,
      the group examined specific endpoints, such as neurotoxicity, immunotoxicity and
      developmental toxicity. The results of the expert group's considerations
      including the development of a guideline to apply the principle are discussed.

PMID- 12052640
TI  - Interactions by carcinogenic metal compounds with DNA repair processes:
      toxicological implications.
AB  - Even though compounds of nickel, arsenic, cobalt and cadmium are carcinogenic,
      their mutagenic potentials are rather weak. In contrast, they exert pronounced
      comutagenic effects, which may be explained by disturbances of different DNA
      repair systems. Thus, cobalt, arsenic, nickel and cadmium interfere with base and
      nucleotide excision repair, even though they affect different steps of the
      respective repair systems and act by different, not yet completely understood
      mechanisms. Potential target molecules for some metal ions are so-called zinc
      finger structures in DNA repair proteins, but each zinc finger protein exerts its
      own sensitivity towards toxic metal ions. Possible consequences of repair
      inhibitions are discussed in more detail for soluble and particulate nickel
      compounds, which have recently been shown to interfere with the repair of stable
      DNA adducts induced by benzo[a]pyrene (B[a]P). Since nickel compounds and
      polycyclic aromatic hydrocarbons such as B[a]P are frequently associated in the
      ambient air, in cigarette smoke and at many workplaces, an impaired removal of
      B[a]P-derived DNA adducts will lead to persistent DNA damage and thus increase
      the risk of mutations and tumor formation.

PMID- 12052641
TI  - Induction of oxidative DNA damage by carcinogenic metals.
AB  - The metal ions carcinogenic to humans are As, Be, Cd, Cr and Ni, and the
      candidates also include Co, Cu, Fe and Pt. A range of molecular mechanisms was
      proposed for these metals, reflecting their diverse chemical properties. The
      oxidative concept in metal carcinogenesis proposes that some complexes of the
      above metals (Co, Cr, Cu, Fe, Ni) formed in vivo undergo redox cycling, yielding
      reactive oxygen species and/or high valence metal ions which oxidize DNA. Some of
      the products of oxidative DNA damage, including 8-oxoguanine and strand breaks,
      induce mutations, which may lead to neoplastic transformation. The establishment
      of metal-binding modes in the cell nucleus and of their reactivity is crucial for
      the understanding of molecular events in metal carcinogenesis. We have proposed
      the binding sites for Ni(II) and Cu(II) in core histones (H3, H2A) and sperm
      protamines (HP2) and, using molecular models, provided evidence for the
      generation of promutagenic oxidative DNA damage by the bound metals.

PMID- 12052642
TI  - Effects of carcinogenic metals on gene expression.
AB  - Six metals and/or their compounds have been recognized as carcinogens: arsenic,
      beryllium, cadmium, chromium, cobalt and nickel. With the exception of arsenic,
      the main rote of exposure is inhalation and the main target organ is the lung.
      Arsenic is exceptional because it also produces tumors of skin and lung after
      oral uptake. With the exception of hexavalent chromium, carcinogenic metals are
      weak mutagens, if at all, and their mechanisms of carcinogenicity are still far
      from clear. A general feature of arsenic, cadmium, cobalt and nickel is their
      property to enhance the mutagenicity and carcinogenicity of directly acting
      genotoxic agents. These properties can be interpreted in terms of the ability of
      these metals to inhibit the repair of damaged DNA. However, because carcinogenic
      metals cause tumor development in experimental animals even under exclusion of
      further carcinogens, other mechanisms have to be envisaged, too. Evidence will be
      discussed that carcinogenic metal compounds alter patterns of gene expression
      leading to stimulated cell proliferation, either by activation of early genes
      (proto-oncogenes) or by interference with genes downregulating cell growth.
      Special reference will be devoted to the effects of cadmium and arsenic on gene
      expression, which have been studied extensively. Possible implications for
      occupational safety and health will be discussed.

PMID- 12052644
TI  - Immunologic basis for autoimmunity and the potential influences of xenobiotics.
AB  - Autoimmune disease may take a variety of forms ranging from organ-specific to
      systemic disorders. Such diseases are believed to be precipitated by a breakdown
      of tolerance and a failure of the immune system to discriminate effectively
      between 'self' and 'non-self'. Susceptibility to autoimmunity is determined by
      both heritable traits and environmental factors, and in this context there has
      been considerable interest in the influences that exposure to drugs and chemicals
      may have on the initiation and/or progression of autoimmune diseases. In this
      article we introduce the adaptive immune system and the concepts of tolerance to
      'self' and autoimmunity. In addition, the mechanisms through which immunological
      tolerance may be compromised are considered.

PMID- 12052643
TI  - Molecular mechanisms of nickel carcinogenesis.
AB  - Humans are exposed to carcinogenic nickel (Ni) compounds both occupationally and
      environmentally. In this paper, molecular mechanisms of nickel carcinogenesis are
      considered from the point-of-view of the uptake of nickel sulfide particles in
      cells, their dissolution and their effects on heterochromatin. Molecular
      mechanisms by which nickel induces gene silencing, DNA hypermethylation and
      inhibition of histone acetylation, will be discussed.

PMID- 12052645
TI  - Predictive testing for autoimmunity.
AB  - Many chemicals, in particular drugs, cause systemic allergy or autoimmune-like
      disorders. Due to complex pathogenesis and strong dependence on genetic make-up,
      these immunotoxicological effects are usually missed in standard toxicity
      testing. Besides, animal studies that demonstrate chemically induced systemic
      allergy or autoimmune-like disorders are scarce. Here, animal models are
      presented that would fit into a predictive two-tiered strategy, designed to allow
      screening for immunostimulatory potential in the first tier, and more elaborate
      testing for allergenic or autoimmunogenic potential of selected chemicals in the
      second tier. The popliteal lymph node assay (PLNA), with or without reporter
      antigens, would fit in the first tier, and relevant route of exposure protocols
      with selected strains of mice or rats may be further developed to compose the
      second tier. To date, the relevant route of exposure models mentioned here (with
      'normal' inbred mice and/or Brown Norway rats) has been tested with only a few
      chemicals, and the PLNA, although tested with over 100 chemicals, is not
      validated as yet. Conceivably, a major challenge in immunotoxicology is to
      incorporate the present knowledge on chemical-induced systemic allergy and
      autoimmunity in further development and validation of predictive models and
      strategies.

PMID- 12052646
TI  - Testing for autoimmunity in humans.
AB  - A number of the autoimmune rheumatic diseases are associated with environmental
      factors, drugs and chemicals. The often non-specific presentation of these
      diseases makes early diagnosis difficult. The availability of serological markers
      such as autoantibodies improves diagnostic ability when taken in context with the
      presenting clinical features. This review focuses on some of the major autoimmune
      rheumatic diseases and their associated autoantibody markers.

PMID- 12052647
TI  - Autoimmunity by pesticides: a critical review of the state of the science.
AB  - The goals of this paper will be to present a critical review of the state of the
      science of pesticides and autoimmunity, and to discuss research that addresses
      the potential links between environmental chemicals and autoimmune disease. To
      date, the science of immunotoxicology has primarily focused on immunosuppression
      and hypersensitivity/allergy, and test methods are available to address these
      outcomes. So much progress has been made to address immunosuppression and contact
      sensitization that there are regulatory guidelines in the U.S. included in the
      registration of pesticides. In contrast, there are no validated approaches to
      assess autoimmunity. The overall objective of this paper will be to use
      pesticides as an important class of environmental chemicals to critically
      evaluate the state of the science for addressing chemical-induced autoimmunity.
      Specific examples of studies with pesticides will be discussed in the context of
      the following types of approaches: animal studies using standard
      immunotoxicological parameters; animal studies using specialized models of
      autoimmunity; human studies after environmental or occupational exposure; and
      human studies after accidental poisoning.

PMID- 12052648
TI  - A tiered approach to assessing children's exposure: a review of methods and data.
AB  - From a public health view, there are many important issues to improving
      children's and adolescent's health, for example, prenatal and childhood
      nutrition, immunizations, infectious disease control, and drug/alcohol/tobacco
      control. There has been increasing emphasis worldwide on protecting children from
      adverse health effects due to environmental factors, including chemicals. For
      well-studied contaminants (e.g. lead) the risks to children are reasonably known
      and appropriate risk management actions, in a public health context, can be
      undertaken. For a number of other chemicals, hazard and exposure data are less
      complete, and risk-based priorities are consequently less substantive. The US
      EPA's Voluntary Children's Chemical Evaluation Program proposal prompted
      additional efforts to develop and improve methods and data for assessing
      children's exposure. The goal is to efficiently identify the substances and
      conditions that present the highest potential risks to children, so that
      resources can be applied efficiently to assure their health improvement. The
      methods we illustrate use an iterative (tiered) approach for (a) screening level
      and (b) more detailed exposure assessments relevant to children. We also review
      and reference the key information sources available for such assessments and
      analyze the information and method's strengths and limitations.

PMID- 12052649
TI  - Occupational versus environmental and lifestyle exposures of children and
      adolescents in the European Union.
AB  - There is recent international concern about specific exposures of children and
      adolescents to toxicants. In general, the situation within the European Union
      appears as follows. (i) OCCUPATIONAL EXPOSURE: Due to regulatory measures, there
      are almost no toxicologically significant occupational exposure situations of
      children to chemical toxicants. This contrasts to the situation in developing
      countries. There is also strict regulation of occupational exposure of
      adolescents (aged under 18). In consequence, the number of potentially exposed
      adolescents has been minimised. (ii) ENVIRONMENTAL EXPOSURE: Specific concern is
      directed towards exposures of infants, especially to neurotoxic heavy metals and
      carcinogens, and there is much regional differentiation of environmental
      exposures. (iii) FOOD: Recent research results are indicative of the general
      progress made in the field of food safety. (iv) INCIDENTAL ACUTE EXPOSURE:
      Besides drugs, household chemicals are a source of incidental acute intoxications
      in children. In Germany, there has been a particular focus on ingestion of lamp
      petroleum oils since 1989. (v) LIFESTYLE: Paramount problems are associated with
      increasing consumption of tobacco (mean age of starting smoking in Germany: 13.6
      years), alcohol (percentage of addicts at ages 12-24 in Germany 6%) and cannabis
      among adolescents, calling for new ways of risk communication. In general, it
      will be necessary to consider children of different ages as separate risk groups.

PMID- 12052650
TI  - Currently available in vitro methods used in the regulatory toxicology.
AB  - About two decades ago in vitro mutagenicity tests were adopted as the first in
      vitro methods in regulatory toxicology. For reasons of animal welfare and better
      science, many validation studies of various in vitro methods were performed
      between 1985 and 1995 for their potential to replace the Draize eye irritation
      test. Albeit the fact that four in vitro methods (HET-CAM, BCOP, IRE, and ECE)
      have gained regulatory tolerance in Europe for the classification of severe eye
      irritants, the lessons learned mainly from these validation studies led to the
      definition of internationally harmonised OECD validation principles and
      acceptance criteria (Final Report of the OECD Workshop on Harmonization of
      Validation and Acceptance Criteria for Alternative Toxicological Tests Methods,
      1996. OECD Publication Office, Paris, France). Application of these principles to
      prevalidation and validation studies, and additional special studies performed in
      Europe with the support of ECVAM, ended in the scientific validation of new in
      vitro methods for the prediction of skin corrosivity and phototoxicity. They were
      accepted for regulatory use in Europe and adopted on 8 June 2000 as test methods
      B. 40 and B. 41 of Annex V of Directive 67/548/EEC. In quite a different
      approach, European industry has submitted in-house validation data to support a
      Draft OECD Test Guideline for in vitro dermal absorption testing, which-after
      peer review and a long lasting international discussion-will now be adopted by
      the OECD. The increasing importance of regulatory measures derived from
      quantitative cytotoxicity tests, and some examples of regulatory accepted in
      vitro methods, where the specific purpose is restricted to a specific regulation
      (e.g. testing of medicinal products, or medical devices), are also addressed.

PMID- 12052651
TI  - The use of in vitro methods for hazard characterisation of chemicals.
AB  - The usual starting points for hazard characterisation are No Observed Adverse
      Effect Levels (NOAELs)/benchmark doses for threshold effects and risk-specific
      doses/unit risks for non-threshold effects. In vitro studies are in general of no
      use in identifying these doses. However, based in part on in vitro investigations
      toxic equivalency factors have been developed for selected halogenated organic
      PCDD/PCDF/PCB congeners. Such factors can be used to determine the total toxic
      equivalent doses of mixtures of these contaminants. Studies with paracetamol
      illustrate that in vitro systems may help in the identification of the most
      sensitive species and strain. In vitro methods have been successfully used to
      studying qualitative and quantitative species differences in the toxicity of
      agents such as peroxisome proliferators and dichloromethane. Investigations with
      a number of chemicals show that in vitro systems are excellent models for
      characterisation of the mode of action of chemicals, but in vitro findings need
      to be validated in vivo. Experiments with bis(tri-n-butyltin)oxide illustrate
      that in vitro systems may aid in the extrapolation from high to low dose and from
      experimental animals to humans. In addition, in vitro approaches can be used to
      obtain useful information on the disposition of xenobiotics. It is concluded that
      if sufficient in vivo mechanistic information is available, in vitro studies
      using sub-cellular fractions/cells/tissue from animals and humans may
      significantly aid in the hazard characterisation of chemicals.

PMID- 12052652
TI  - In vitro preclinical lead optimisation technologies (PLOTs) in pharmaceutical
      development.
AB  - The explosion of genuine high throughput technologies has allowed large compound
      libraries to be screened with ever increasing biological specificity,
      exacerbating the problem of lead candidate selection for subsequent drug
      development. To avoid creating a bottleneck, compounds identified from the high
      throughput screens undergo lead optimisation, a medium-throughput screen which
      allows ranking in terms of their basic absorption, distribution, metabolism,
      excretion (ADME) and toxicological properties. The historical role of the
      preclinical scientist in the drug discovery/development continuum has been to
      perform ADME and toxicology studies, simply to support the regulatory submission
      of lead candidates. This situation is, however, changing with the development of
      preclinical lead optimisation technologies (Approaches to High Throughput
      Toxicity Screening, London, Atterwill et al., 1999) facilitating the selection of
      leading candidates, thereby bridging the gap between high throughput efficacy
      screens and traditional safety assessment programmes.

PMID- 12052653
TI  - In vitro toxicology methods: impact on regulation from technical and scientific
      advancements.
AB  - The impressive advancement of technologies in biomedical research, and
      particularly in the area of in vitro experimental models, has opened up new
      possibilities related to co-cultures, micromass or stem cell cultures. Engineered
      cells to study specific targets and/or mechanisms are also available. Moreover, a
      very subtle approach in the study of toxicological effects is represented by the
      very recent genomics and proteomics techniques. New mechanistically based methods
      could be established from all these approaches, which, once validated, could
      enter the regulatory procedure. So far, in toxicology, only a few in vitro tests
      are accepted for regulatory purposes, such as those related to corrosion,
      phototoxicity and absorption. Many others are in the pre-validation or validation
      phase. An area where in vitro tests play a key role is the genetic toxicology. In
      this context, the most recent testing strategies and test methods will be
      presented, with particular attention to the recently updated guidelines for food
      additives by the EU Scientific Committee on Food. An improvement in the
      implementation of validated methods could arise from a better coordination on the
      matter at national and international levels, the harmonisation of different
      legislations, and a strict control of the national rules in order to make them up
      to-date with respect to validated methods.

PMID- 12052654
TI  - An EU perspective on the use of in vitro methods in regulatory pharmaceutical
      toxicology.
AB  - Some in vitro methods such as those used in the assessment of genotoxicity,
      receptor-binding and QT-prolongation are well established in regulatory
      pharmaceutical toxicology. In vitro systems to study metabolic profiles, P450
      isoforms, drug interactions, etc. or to provide metabolic activation in
      genotoxicity assays are extremely useful, but are subject to a number of
      important limitations. In vitro models are also employed on an ad-hoc basis for
      other purposes, for example, to help investigate mechanisms underlying in vivo
      findings. At the current stage of technical development of alternative methods,
      rapid replacement of the pivotal animal studies used in drug safety assessment
      seems unlikely. The existing in vivo models have good predictive ability
      regarding toxic effects in humans, are underpinned by an extensive literature and
      form the basis of most regulatory toxicology guidelines. Integrated in vitro
      testing strategies, meant to replace conventional repeated-dose studies, are
      still relatively undeveloped. Emerging technologies such as transgenics,
      toxicogenomics and toxicoproteomics, although they rely on the continued use of
      animals, have considerable potential in terms of reduction and refinement of in
      vivo methods.

PMID- 12052655
TI  - Introduction of in vitro data into local irritation/corrosion testing strategies
      by means of SAR considerations: assessment of chemicals.
AB  - The European legislation on control and evaluation of chemicals requires hazard
      and risk assessment of chemicals for human health and the environment. Technical
      guidance on carrying out this assessment includes the use of information based on
      results of testing with animals and on results of alternatives to animal testing.
      Within regulatory risk assessment the use of in vitro data for hazard and risk
      classification purposes is in the very beginning, because in vitro results do not
      mirror the total of effects observed in standardised animal tests, and hence
      cannot be easily related to current regulatory classification criteria. In vitro
      tests aim at the detection of only a few aspects considered crucial for the
      formation of a very complex health hazard observed in vivo. Therefore, they need
      a clear definition of the toxicological questions they can answer and of the
      limits of their evidence with respect to meeting regulatory classification
      criteria. In order to enhance the use of in vitro results within the regulatory
      classification procedure, the Organisation for Economic Co-operation and
      Development (OECD) developed tiered testing and assessment strategies that
      combine in vitro results and structure-activity relationship (SAR)
      considerations.

PMID- 12052656
TI  - The use and interpretation of in vitro data in regulatory toxicology: cosmetics,
      toiletries and household products.
AB  - There is currently a drive to eliminate animal testing for cosmetics, toiletries
      and household products; indeed, the European Union Cosmetics Directive aims to
      prohibit the use of experimental animals for the testing of finished cosmetic
      products after 2002. At present, national prohibitions are in place in the UK,
      Germany, Austria and the Netherlands, for the testing of finished cosmetic
      products and cosmetic ingredients. In the USA animal testing for certain types of
      finished products is mandatory. Against this background, the currently available
      regulatory in vitro tests comprise methods for eye irritation, skin corrosivity,
      genotoxicity, dermal penetration and photoirritation. The draft updates to the
      Organisation for Economic Co-operation and Development guidelines for eye and
      skin irritation advocate the use of in vitro or ex vivo methods prior to the
      commencement of animal studies. At present, testing for these endpoints cannot be
      completed in vitro, but potentially corrosive substances and products can be
      classified without the need for animal studies. Regulatory genotoxicity testing
      can be completed using only in vitro methods, provided that a clear negative
      outcome is obtained for each test. Data from dermal penetration studies may be
      used to refine risk assessments. Current developments in areas such as skin
      sensitisation and skin irritation promise that in the reasonably near future such
      information may be generated without the use of animals.

PMID- 12052657
TI  - Age-related sensitivity of the nervous system to neurotoxic insults.
AB  - Complex genomic activity and environmental factors regulate neuronal plasticity,
      which operates during pre- and postnatal development, can be reactivated after
      injury, and is impaired during aging. In these contexts, the effects of chemicals
      are often unpredictable because the developing and aging nervous system may or
      may not be equally susceptible as that of the adult. Thus, the developing central
      nervous system may be more susceptible to the acute toxicity of certain
      organophosphorus esters, whereas the developing peripheral nervous system is
      resistant to organophosphate-induced delayed polyneuropathy. Reasons for age
      related susceptibility are manifold, including both differences in toxicokinetics
      and toxicodynamics and in intrinsic susceptibility of the nervous system, which
      is related to given physiological conditions. Therefore, the identification of
      genetic and environmental factors regulating neuronal plasticity becomes critical
      to the understanding of age-related sensitivity to chemicals. The example of age
      related sensitivity to organophosphate-induced delayed polyneuropathy is
      illustrated together with that of the promotion of axonopathies by certain
      esterase inhibitors, which also seem modulated according to age. The
      identification of the molecular targets of both organophosphate neuropathy and
      promotion of neuropathy might allow the understanding of processes involved in
      the expression of peripheral neurotoxicities according to age.

PMID- 12052658
TI  - Apoptosis and age-related disorders: role of caspase-dependent and caspase
      independent pathways.
AB  - The execution of the apoptotic program involves a relatively limited number of
      pathways that converge on the activation of the caspase family of proteases.
      However, there is increasing evidence that other protease families may contribute
      to produce apoptotic-like features. This has posed the question as to whether
      caspase inhibitors may then be used to treat diseases characterised by an excess
      apoptosis. In several neurodegenerative diseases including acute neuronal loss as
      in stroke or slowly developing diseases at least two major events contribute to
      neurodegeneration: the loss of neuronal connectivity and cell loss. In many of
      these conditions, mitochondrial dysfunction and the resulting ATP depletion may
      preclude caspase activation, and consequently switch execution of cell death
      towards necrosis. A block or partial inhibition of the typical apoptotic demise
      may have profound implications in vivo, as persistence within the nervous system
      of damaged, but 'undead' cells, followed by delayed lysis may favour
      neuroinflammatory reactions. Furthermore, caspases may be involved in loss of
      neurons, but not in the loss of connectivity that seems to initiate degenerative
      processes in the nervous system. Some recent findings, which suggest that
      degenerating neurons may use multiple execution pathways will be discussed.

PMID- 12052659
TI  - Developmental neurotoxicity: do similar phenotypes indicate a common mode of
      action? A comparison of fetal alcohol syndrome, toluene embryopathy and maternal
      phenylketonuria.
AB  - Developmental neurotoxicity can be ascribed to in utero exposure to exogenous
      substances or to exposure of the fetus to endogenous compounds that accumulate
      because of genetic mutations. One of the best recognized human neuroteratogens is
      ethanol. The Fetal Alcohol Syndrome (FAS) is characterized by growth deficiency,
      particular facial features, and central nervous system (CNS) dysfunctions (mental
      retardation, microencephaly and brain malformations). Abuse of toluene by
      pregnant women can lead to an embryopathy (fetal solvent syndrome, (FSS)) whose
      characteristics are similar to FAS. Phenylketonuria (PKU) is a genetic defect in
      phenylalanine (Phe) metabolism. Offspring of phenylketonuric mothers not under
      strict dietary control are born with maternal PKU (mPKU), a syndrome with similar
      characteristics as FAS and FSS. While ethanol has been shown to cause neuronal
      death, no such evidence is available for toluene or Phe and/or its metabolites.
      On the other hand, alterations in astrocyte proliferation and maturation have
      been found, mostly in in vitro studies, which may represent a potential common
      mode of action for at least some of the CNS effects found in FAS, mPKU, and FSS.
      Further in vivo and in vitro studies should validate this hypothesis and
      elucidate possible molecular targets.

PMID- 12052660
TI  - Nicotine and neurodegeneration in ageing.
AB  - Impairment in cholinergic systems is a highly consistent finding in human
      dementia. Among cholinergic markers, marked decreases in nicotine binding have
      been most consistently observed in the telencephalic regions of demented patients
      and are thought to contribute to the cognitive deficits associated with ageing
      and age-related neurodegenerative diseases. New evidence that the cholinergic
      system has a specific pathogenic role in the neurodegenerative alterations of
      aged and, especially, demented patients is fast accumulating. Both in vivo and in
      culture, nicotine protects striatal, hippocampal and cortical neurons against the
      neurotoxicity induced by excitotoxic amino acids as well as the toxicity caused
      by beta-amyloid, the major component of senile plaques. Further support for the
      implication of nicotinic receptors in brain ageing is come from recent studies on
      transgenic animals lacking nicotinic receptor subtypes, which shed light on the
      mechanisms of nicotine neuroprotection and neurotoxicity.

PMID- 12052661
TI  - Tissue-specific estrogenic response and molecular mechanisms.
AB  - Estrogens exert profound effects on growth, differentiation, and function of many
      reproductive tissues. They also affect other tissues, including bone, liver,
      cardiovascular system, and brain. In the last few years it has been demonstrated
      that several synthetic estrogens can act in a tissue-specific manner. The first
      example of such a selective estrogen receptor modulator (SERM) was tamoxifen, for
      which an estrogen agonist-like activity in the endometrium and bone was seen to
      occur simultaneously with an estrogen antagonist activity in the breast. The
      mechanisms by which the same compound can exert tissue-specific agonist and
      antagonist actions are still being investigated. Important aspects include the
      interaction of the ligand with the two estrogen receptor subtypes and the
      interaction of these ligand-receptor complexes with effectors, which include
      different DNA response elements and important coregulator proteins. In addition
      to well-documented effects on gene transcription, there is evidence that estrogen
      receptors and other estrogen binding proteins are involved in some rapid, non
      genomic effects of estrogens in target cells. For these reasons it is important
      to point out that a toxicological evaluation of endocrine modulators should
      include an analysis of potential SERM-like properties.

PMID- 12052662
TI  - Integration of mechanistic data in the toxicological evaluation of endocrine
      modulators.
AB  - Controversy has arisen concerning the likelihood of adverse health effects due to
      exposure to hormonally active agents or endocrine modulators such as
      environmental estrogens. With the aim to improve the basis for their
      toxicological evaluation, several chemicals of anthropogenic (bisphenol A,
      octylphenol, o,p'-DDT) and of natural origin (daidzein, genistein) were
      investigated with regard to their mode of hormonal action and potency as well as
      toxicokinetics. Experimental toxicodynamic and toxicokinetic data illustrate
      important points in a comparative assessment of environmental estrogens. A novel
      concept, the Hygiene-Based Margine of Safety (HBMOS), has been suggested to
      characterize the relative impact of these potential endocrine modulators on human
      health: It integrates exposure scenarios (i.a. those generated within the
      European Existing Chemicals Programme) and in vivo rodent potency data for
      xenoestrogens and for dietary phytoestrogens. On the basis of these informations,
      HBMOS values calculated for the alkylphenol and bisphenol A appear sufficiently
      high to ensure the absence of a practical risk to human health under the present
      exposure conditions. For slowly accumulating compounds (e.g. DDT) with much
      longer half-lifes than isoflavones, such comparison should be based on
      comparative blood levels rather than on scenarios of daily exposures.

PMID- 12052663
TI  - Identification of end points relevant to detection of potentially adverse drug
      reactions.
AB  - Expectations are high that the use of proteomics, gene arrays and metabonomics
      will improve risk assessment and enable prediction of toxicity early in drug
      development. These molecular profiling techniques may be used to classify
      compounds and to identify predictive markers that can be used to screen large
      numbers of chemicals. One of the challenges for the scientific community is to
      discriminate between changes in gene/protein expression and metabolic profiles
      reflecting physiological/adaptive responses, and changes related to pathology and
      toxicology. In these proceedings we provide a brief overview of the technologies
      with focus on proteomics and the possible applications to mechanistic and
      predictive toxicology. The discussion also includes strengths and limitations of
      molecular profiling technologies.

PMID- 12052664
TI  - What do we want from proteomics in the detection and avoidance of adverse drug
      reactions.
AB  - The incidence of severe adverse drug reactions is approximately 7% in hospital
      patients. In many cases the adverse event is difficult to predict or even explain
      on the basis of the known pharmacology of the causative agent. It is not
      infrequent in the context of multiple drug therapy, which complicates
      identification of the culprit. This can present a major problem in the management
      of chronic diseases such as tuberculosis or epilepsy. Pharmacogenetics offers one
      approach to reducing the incidence of drug-induced adverse reactions but has
      recognised limitations as a predictive tool and little role in diagnosis.
      Proteomics may have some predictive value but is likely to be of greater use in
      diagnosis-for example by recognising a drug signature in an accessible tissue.
      This may be possible on a blood sample or biopsy taken at presentation.
      Alternatively an in vitro assay that replaced rechallenging the patient with a
      drug would be helpful. The goal is to identify the causative drug permitting
      resumption of treatment with a safer alternative.

PMID- 12052665
TI  - Lung diseases due to environmental exposures to erionite and asbestos in Turkey.
AB  - Asbestos deposits have been used locally by the rural inhabitants of Central and
      Southeastern Anatolia for domestic purposes for many years. Mineralogical
      analysis revealed that tremolite is the most prominent asbestos type found in the
      region. There is in addition another mineral fiber found particularly in three
      villages located in the Cappadocian region of Central Anatolia (zeolite
      villages). This is a non-asbestos mineral, which has been identified as the
      fibrous zeolite, erionite. This fiber is present in the volcanic tuffs, which are
      used as building stone. Hence, exposure to erionite fibers is always possible in
      the houses, annexes, and streets of the villages. It has been demonstrated that
      both asbestos and erionite cause a variety of benign and malignant chest
      diseases. Among the diseases, calcified pleural plaques (CPP) are the most
      frequently seen and may be used as an indicator of mineral fiber exposure.
      Asbestos and erionite exposure are the main causes of malignant mesotheliomas in
      Turkey. In zeolite villages malignant mesothelioma is responsible for more than
      50% of the total deaths. A recent study showed that simian virus 40 is not a
      cofactor in the pathogenesis of environmental malignant mesothelioma in Turkey.
      An additional recent genetic-epidemiological study showed that there are some
      families, which are genetically predisposed to mesothelioma.

PMID- 12052666
TI  - Biodegradability of inhaled p-aramid respirable fiber-shaped particulates (RFP):
      mechanisms of RFP shortening and evidence of reversibility of pulmonary lesions.
AB  - These studies elucidated mechanisms of inhaled p-aramid respirable fiber-shaped
      particulates (RFP) biodegradation in the lungs of exposed rats and hamsters. We
      postulate that lung fluids coat/activate inhaled p-aramid RFP which deposits in
      the lung and promote enzymatic attack and consequent shortening. p-Aramid or
      cellulose (biopersistent control) RFP were instilled into the lungs of rats and
      the lungs digested 24 h later using two different (KOH or enzymatic) digestion
      techniques. In vivo, the enzyme but not the KOH solution produced shortening of p
      aramid but not cellulose RFP recovered from the lungs. For in vitro studies, the
      two RFP-types were incubated with BAL fluids and underwent simulated digestions;
      also rat lung epithelial cells, macrophages or co-cultures were incubated with p
      aramid and digested at 1, 24, or 168 h postexposure. The results of in vitro
      acellular studies demonstrated that only p-aramid RFP incubated in BAL fluids and
      digested by the enzyme method were shortened. In vitro cellular studies
      demonstrated a shortening of p-aramid RFP in macrophages and co-cultures but not
      in lung epithelial cells at 24 h and 1 week postexposure. These results
      demonstrate that lung fluids coat and catalyze the p-aramid RFP as a prelude for
      shortening and describe a likely mechanism for the biodegradability of inhaled p
      aramid RFP in the lungs of exposed animals.

PMID- 12052667
TI  - Clinical toxicological aspects of fluoroquinolones.
AB  - Reactions of the gastrointestinal tract and the central nervous system are the
      most often observed adverse effects during therapy with fluoroquinolones.
      Pathogenesis of the neurotoxic effects of fluoroquinolones could be related to
      the activation of the NMDA receptor. Animal experiments as well as clinical
      experience show that the cardiotoxic potentials of sparfloxacin and grepafloxacin
      are higher than those of the other fluoroquinolones: they cause QT prolongation
      at rather low doses thus increasing the risk for severe arrhythmia (torsades de
      pointes). Phototoxicity has been described for all quinolones, but derivatives
      with a halogen atom at position 8 show the highest potential for such reactions
      (e.g. clinafloxacin). Chondrotoxicity of quinolones can affect the articular
      cartilage and the epiphyseal growth plate in immature animals; the use of these
      drugs in pediatrics should be restricted to carefully selected indications (such
      as the use of ciprofloxacin in cystic fibrosis). Tendinitis and tendon ruptures
      can also be induced by quinolones. Overall, quinolones are as well tolerated as
      most other anti-microbial agents. However, their specific toxic potentials have
      to be considered when they are chosen for treatment of bacterial infections.

PMID- 12052668
TI  - Cardiotoxicity of new antihistamines and cisapride.
AB  - Although the new second-generation nonsedative antihistamines terfenadine and
      astemizole were launched as highly selective and specific H(1)-receptor
      antagonists, they were later found to cause prolongation of the QT-interval and
      severe cardiac arrhythmias. The prolongation of the QT-interval is caused by the
      blockade of one or more of the cardiac potassium channels, among which the
      delayed rectifier I(Kr), encoded by the HERG-gene, appears to be the most
      significant. The potency of the prokinetic drug cisapride to block I(Kr) appears
      to be similar to that of terfenadine (IC(50) about 50 nmol/l). These drugs cause
      problems when overdosed, used in combination with inhibitors of their CYP3A4
      mediated metabolism, or when given to individuals with altered drug kinetics (the
      aged) or patients with existing cardiac disease (congenitally long QT). Moreover,
      interactions with other QT-interval prolonging drugs require special attention.
      Active hydrophilic metabolites of the second-generation antihistaminic compounds
      (ebastine-carebastine, loratadine-desloratadine, terfenadine-fexofenadine,
      astemizole-norastemizole) are new compounds with probably reduced risk for drug
      interactions and cardiac toxicity.

PMID- 12052669
TI  - Specific neurotoxicity of chronic use of ecstasy.
AB  - The use of the illicit drug ecstasy (mainly containing
      methylenedioxymethamphetamine, MDMA) is widespread among young people in western
      Nations. Animal experiments indicate that MDMA is a potent neurotoxin
      specifically affecting the serotonergic system. A few functional neuroimaging
      studies revealed central nervous alterations after the repeated use of ecstasy.
      We examined 94 ecstasy users in comparison to 27 control subjects by means of
      positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG).
      The FDG uptake rates were globally reduced in ecstasy users, most pronounced in
      the striatum. The uptake rates tended to be negatively correlated with the
      cumulative ecstasy doses. The results indicate that younger ecstasy users may be
      more vulnerable with regard to neurotoxicity.

PMID- 12052670
TI  - New developments in the therapy of intoxications.
AB  - There has been a significant evolution in the clinical management of the poisoned
      patient over the last decade. Interventions that were once the cornerstone of
      treating the poisoned patient have become passe or have come under intense
      scrutiny. The advent of evidence-based medicine has forced clinical scientists to
      re-evaluate standard therapies. Gastrointestinal decontamination with either
      emesis or gastric lavage was the foundation of the initial management of most
      poisoned patients. Examination of the published literature demonstrated that
      neither emesis nor lavage changed the ultimate outcome of poisoned patients, and
      most poison centers have abandoned their use. Even the use of activated charcoal
      has been questioned. A multitude of studies demonstrated that the effectiveness
      of activated charcoal diminished significantly 30-60 min after the ingestion of a
      poison. No study has demonstrated that charcoal changed patient outcome.
      Cathartics have been deemed to be ineffective and potentially dangerous and are
      never indicated. Whole bowel irrigation should not be used routinely in the
      management of the poisoned patient. Multiple dose activated charcoal and urinary
      alkalinization, commonly used to enhance the elimination of some poisons, have
      limited usefulness. While these 'old' and more general methods of
      'detoxification' have thus failed in most cases to improve or change patient
      outcome, the use of more specific antidotes, tailored to the exact cause of
      intoxication is to be considered. Very few antidotes, however, are used on a
      consistent basis in the management of poisoned victims. The indiscriminate use of
      antidotes may even be harmful to the patient and incur an inordinate expense. In
      addition to the commonly known antidotes N-acetylcysteine (acetaminophen,
      paracetamol), naloxone (opioids) and flumazenil (benzodiazepines), new antidotes
      include fomepizole to treat ethylene glycol and methanol poisoning and Crotalidae
      Polyvalent Immune Fab (Ovine) for pit viper envenomation.

PMID- 12052671
TI  - Ethical issues for bioscientists in the new millennium.
AB  - The scientific understanding of biological processes is developing extremely
      fast, providing opportunities for changing people's lives in many ways-through
      health care, food and the environment. The speed with which these changes are
      occurring means that even bioscientists can only keep up with their own narrow
      field of science. It is not surprising that members of the public are frightened
      about the rapidity and impact of the changes arising from the biological
      revolution. These concerns are often expressed in ethical terms. Decision making
      about the direction of research and its application is becoming more transparent.
      This means that bioscientists will have to engage in the debate about their work
      with members of the public, including those who are opposed to it, in order to
      create acceptance of their work and its products. At the moment, bioscientists
      are often ill equipped to enter this debate because of their lack of training in
      ethics and lack of understanding of the impact of ethics on their work. A better
      understanding of bioethics will be necessary for entering this debate with
      vigour. A comprehensive ethical analysis is outside the scope of this text. Some
      of the principal arguments about the ethics of two aspects of bioscience research
      genetically modified crops and the use of experimental animals-will be discussed
      to illustrate a few of the issues that derive from ethical analyses. I hope that
      this will encourage toxicologists to take a greater interest in bioethics.

PMID- 12052672
TI  - Structure of epidemiological studies on genetic susceptibility to environmental
      toxicants.
AB  - Metabolic genes code for enzymes that are involved in conjugation and
      detoxification of environmental toxicants. Polymorphisms in these genes result in
      individual differences in susceptibility to carcinogens and therefore in
      differences in cancer risk. The most common study design used in the area of
      genetic susceptibility is the case-control study, because of both economic and
      logistic constraints. Since metabolic gene polymorphisms are germ line mutations
      that are present before the onset of the disease, this study design is
      applicable, and the assessment of the polymorphism can be performed after
      diagnosis. Since the polymorphism interacts with the exposure through type 2 gene
      environment interaction, and in the absence of exposure the polymorphism alone
      has no effect on the risk of disease, the measurement of the relevant exposure is
      mandatory. Relevant exposures can be measured according to the classical
      epidemiological methods, or by means of specific biomarkers, and therefore biases
      and confounders have to be taken into account in both design and analysis of the
      study, like in classic epidemiologic studies.

PMID- 12052673
TI  - Genetic susceptibility to environmental toxicants: the interface between human
      and experimental studies in the development of new toxicological concepts.
AB  - The growing knowledge of the genetic polymorphisms of enzymes metabolising
      xenobiotics in humans and their connections with individual susceptibility
      towards toxicants has created new and important interfaces between human
      epidemiology and experimental toxicology. The results of molecular
      epidemiological studies may provide new hypotheses and concepts, which call for
      experimental verification, and experimental concepts may obtain further proof by
      molecular epidemiological studies. If applied diligently, these possibilities may
      be combined to lead to new strategies of human-oriented toxicological research.
      This overview will present some outstanding examples for such strategies taken
      from the practically very important field of occupational toxicology. The main
      focus is placed on the effects of enzyme polymorphisms of the xenobiotic
      metabolism in association with the induction of bladder cancer and renal cell
      cancer after exposure to occupational chemicals. Also, smoking and induction of
      head and neck squamous cell cancer are considered.

PMID- 12052674
TI  - Current and future benefits from the use of GM technology in food production.
AB  - For the current generation of genetically modified (GM) crops the improvement of
      agronomic traits (e.g. herbicide tolerance, insect resistance) has been a major
      objective. The lack of obvious and direct benefits for the consumer has been a
      main point of criticism. Future trends will increasingly encompass the
      modification of quality traits, such as the improvement of sensory and especially
      nutritional properties. Some of the ongoing developments try to meet the desire
      of consumers for 'healthy' or 'high-tech' foods in developed countries. Others
      are intended to assist in adjusting the nutritional status of foods to the needs
      of consumers in developing countries. Considering the increasing world population
      and the limited amount of arable land, GM technology may also become a valuable
      tool to ensure food security. The major prerequisite for the applicability of the
      technique is the safety of the resulting products. The increasing complexity of
      modifications intended might require adjustments and improvements of the
      strategies applied to the safety assessment of GM foods. Present research
      activities try to meet these new challenges.

PMID- 12052675
TI  - Clinical risk assessment of GM foods.
AB  - The main concerns about adverse effects of genetically modified (GM) foods on
      health are the transfer of antibiotic resistance, toxicity and allergenicity.
      There are two issues from an allergic standpoint. First, the transfer of a known
      allergen may occur from a crop into a non-allergenic target crop. The second
      scenario is the creation of a neo-allergen where de novo sensitisation occurs in
      the population. The first scenario occurred in 1996 when the 2S albumen protein
      from Brazil nut was transferred into soy bean (N. Engl. J. Med. 334 (1996) 688).
      2S albumen was found to be a major Brazil nut allergen and the newly expressed
      protein in transgenic soy retained its allergenicity. Patients allergic to Brazil
      nuts and not to soy bean now showed an IgE mediated response towards GM soy bean.
      We argue that it is possible to prevent such occurrences by doing IgE-binding
      studies and taking into account physico-chemical characteristics of proteins and
      referring to known allergen databases. The second possible scenario of de novo
      sensitisation does not easily lend itself to risk assessment. We compare GM
      technology to traditional plant breeding and food processing methods. There is no
      evidence that the technology used for the production of GM foods poses an
      allergic threat per se compared to other methodologies widely accepted in the
      food industry. We need to proceed cautiously in the future, assessing individual
      GM foods on the basis of their individual merits and risks prior to introducing
      them into the market.

PMID- 12052677
TI  - Experience with environmental issues in GM crop production and the likely future
      scenarios.
AB  - In the Cartagena Protocol on Biosafety, standards for risk assessment of
      genetically modified organisms (GMOs) have been set. The criteria and information
      basis for the risk assessment of GMOs have been modified by the EU Directive
      2001/18/EC. Various approaches to further improve the criteria for environmental
      risk assessment of GMOs are described in this study. Reports on the ecological
      impacts of the cultivation of certain non-transgenic crop plants with novel or
      improved traits as analogy models to transgenic plants showed that the effects of
      agricultural practice can be at least equally important as the effects of gene
      transfer and invasiveness, although the latter currently play a major role in
      risk assessment of transgenic crops. Based on these results the applicability of
      the methodology of 'Life Cycle Analysis (LCA)' for genetically modified plants in
      comparison with conventionally bred and organically grown crop plants was
      evaluated. The methodology was regarded as applicable with some necessary future
      improvements. In current projects, the assessment of toxicology and allergenicity
      of GM crops are analysed, and suggestions for standardization are developed.
      Based on results and recommendations from these efforts there are still the
      challenges of how to operationalize the precautionary principle and how to take
      into account ecologically sensitive ecosystems, including centres of origin and
      centres of genetic diversity.

PMID- 12052676
TI  - Regulatory control of genetically modified (GM) foods: likely developments.
AB  - The placing of genetically modified (GM) crops on the European market requires a
      regulatory approval supported by a thorough safety evaluation. This approach has
      been applied to all GM crops presently on the market. Despite this stringent
      process there has been an increasing public concern about the impact of GM foods
      on human health and the environment. In this context, regulatory control may
      develop in several directions. One response to the public concern is to
      strengthen the data requirements for the risk assessment process. Several avenues
      have been proposed. They include the application of technologies such as
      proteomics and metabolomics to assess unintended changes, and the development of
      predictive methods to evaluate allergenicity. Obligations for post-launch
      surveillance have appeared in regulations. Criteria are required to define when
      and why such approaches are necessary. Significant challenges including
      feasibility and validation of the methods, and safety relevance of the data
      generated will have to be addressed before any general application of these new
      approaches. Effective monitoring requires the ability to identify the presence of
      GM products and trace their origin. Traceability and labeling are therefore
      important developments in the GM food regulatory arena. Both require the
      development of reliable analytical detection tools.

PMID- 12052678
TI  - Degradation of phenol by Rhodococcus erythropolis UPV-1 immobilized on Biolite in
      a packed-bed reactor.
AB  - A strain of Rhodococcus erythropolis has been isolated and identified by 16S rRNA
      sequencing. Cells acclimated to phenol can be adsorbed on the external surface of
      beads of the ceramic support Biolite where they grow forming a network of large
      filaments. Exponentially-growing cells were adsorbed faster than their stationary
      phase counterparts. Immobilization resulted in a remarkable enhancement of the
      respiratory activity of cells and a shorter lag phase preceding the active phenol
      degradation. Under optimum operation conditions, the immobilized cells in a
      laboratory-scale column reactor packed with support beads were able to degrade
      completely phenol in defined mineral medium at a maximum rate of 18 kg phenol m(
      3) per day. The performance of the bioreactor in long-term continuous operation
      was characterized by pumping defined mineral medium which contained different
      concentrations of phenol at different flow-rates. Once phenol biodegradation in
      defined mineral medium was well established, an industrial wastewater from a
      resin manufacturing company, which contained both phenol and formaldehyde, was
      tested. In this case, after wastewater conditioning (i.e. pH, nitrogen source and
      micronutrient amendments) the immobilized cells were able to remove completely
      formaldehyde and to partly biodegrade phenols at a rate of 1 kg phenol m(-3) per
      day.

PMID- 12052679
TI  - Metabolic active-high density VERO cell cultures on microcarriers following
      apoptosis prevention by galactose/glutamine feeding.
AB  - The control of cell death occurring in high density cultures performed in
      bioreactors is an important factor in production processes. In this work, medium
      nutrient removal or feeding was used to determine at which extension apoptosis
      could be, respectively, involved or prevented in VERO cell cultures on
      microcarriers. Glutamine and galactose present in the VERO cell culture medium
      was consumed after, respectively, 6 and 12 days of culture. Kinetics studies
      showed that fresh medium replacement and, to some extent, galactose or glutamine
      depleted-fresh medium replacement provided a nutritional environment, allowing
      the VERO cell cultures to attain high densities. Galactose was shown to be a more
      critical nutrient when cultures reached a high density. In agreement with that,
      VERO cell cultures supplemented with galactose and/or glutamine were shown to
      confirm previous findings and, again at high densities, galactose was shown to be
      a critical nutrient for VERO cell growth. These observations also indicated that
      in VERO cell cultures, for feeding purposes, the glutamine could be replaced by
      galactose. The inverse was not true and led, at high densities, to a decrease of
      cell viability. In the absence of glutamine and galactose, apoptosis was observed
      in VERO cell cultures by cytofluorometry, Acridine orange staining or light and
      electron microscopy, reaching high levels when compared to cultures performed
      with complete medium. VERO cells apoptosis process could be prevented by the
      galactose and/or glutamine feeding and, at high densities, galactose was more
      efficient in protecting the cultures. These cultures, prevented from apoptosis,
      were shown to synthesize high levels of measles virus following infection. Our
      data show that apoptosis prevention by glutamine/galactose feeding, led to high
      productive and metabolic active VERO cell cultures, as indicated by the high cell
      density obtained and the virus multiplication leading to higher virus titers.

PMID- 12052680
TI  - A fibrous-bed bioreactor for continuous production of developmental endothelial
      locus-1 by osteosarcoma cells.
AB  - Genetically engineered human osteosarcoma cells containing developmental
      endothelial locus-1 (del-1) gene were studied for production of Del-1, a protein
      that has the properties of an extracellular matrix protein and can regulate
      vascular morphogenesis and remodeling. Del-1 has been studied as a potential anti
      angiogenesis drug targeting solid tumors. In this study, osteosarcoma cells were
      cultured in a fibrous-bed bioreactor (FBB) to continuously produce Del-1. The FBB
      was constructed by packing a polyester fibrous matrix into a 1.5-l spinner flask.
      The effects of media composition, including the serum content in the medium, and
      dilution rate on cell growth, metabolism, and Del-1 production were studied. A
      gradual reduction of serum content from 10% (v/v) to 0.5% (v/v) caused no loss in
      Del-1 production. However, the production of Del-1 decreased significantly in a
      serum-free medium, suggesting some nutrients present in the serum were important
      to culture viability and Del-1 production. The continuous FBB culture was stable
      for long-term production of Del-1, with a higher Del-1 titer than that normally
      obtained in T-flask cultures and overall productivity similar to the total
      production from 300 25-cm(2) T-flasks. Reducing geneticin in the medium from 250
      microg ml(-1) to zero at later culturing stages had no significant effect on Del
      1 production. The FBB was operated for a period of more than 4 months without any
      notable degeneration, and reached a final cell density of 3 x 10(8) cells ml(-1)
      of packing volume with >90% cell viability. The good reactor performance can be
      attributed to the three-dimensional environment provided by the fibrous matrix
      that allows for efficient mass transfer and cell immobilization and growth.
      Scanning electron microscopic and confocal scanning laser microscopic studies of
      the cell-matrix showed that cells formed large aggregates in the fibrous matrix
      and cell density was relatively uniform in the matrix.

PMID- 12052681
TI  - Enhanced expression of exogenous genes from retroviruses using HIV2/Tat.
AB  - The capacity to produce large amounts of protein in mammalian cells is important
      in several contexts, including large-scale generation of biologically useful
      proteins, gene therapy, and transdominant genetics in cultured cells. For
      transdominant genetics, retroviral vectors are especially useful for delivery of
      expression libraries. However, even the potent CMV promoter is often unable to
      stimulate single-copy production of protein beyond the 1 microM level. We have
      adapted the HIV2/Tat expression system to retroviral vectors to boost expression
      above levels attainable with CMV promoters. We show that the system produces
      protein levels in four cell types tested which exceed levels attained by wild
      type CMV or modified CMV promoters. In one cell line, the increase is 10-fold
      above CMV. Coupled with a stable expressed protein, levels of about 4 microM can
      be produced from presumptive single-copy retroviral transductants, and 30 microM
      from multicopy transductants.

PMID- 12052682
TI  - Heterologous production of two unusual acyclic carotenoids, 1,1'-dihydroxy-3,4
      didehydrolycopene and 1-hydroxy-3,4,3',4'-tetradehydrolycopene by combination of
      the crtC and crtD genes from Rhodobacter and Rubrivivax.
AB  - Acyclic hydroxy carotenoids were produced from lycopene and 3,4-didehydrolycopene
      in Escherichia coli by combining different carotenogenic genes including the
      carotene hydratase gene crtC and the carotene 3,4-desaturase gene crtD. The genes
      originated either from Rhodobacter species or Rubrivivax gelatinosus. It was
      shown that the product of crtD from Rubrivivax unlike the one from Rhodobacter is
      able to convert 1-HO-3,4-didehydrolycopene to 1-HO-3,4,3',4'-tetradehydrolycopene
      (=3,4,3',4'-tetradehydro-1,2-dihydro-psi,psi-caroten-1-ol). Thus, only when the
      desaturase from Rubrivivax is expressed can this novel carotenoid be obtained. In
      the presence of crtC from Rubrivivax, another carotenoid 1,1'-(HO)(2)-3,4
      didehydrolycopene (=3,4-didehydrolycopene-1,2,1',2'-tetrahydro-psi,psi-caroten
      1,1'-diol) not found in a non-transgenic organism before is formed in E. coli.
      Its accumulation under these conditions and its absence when crtC from Rubrivivax
      is replaced by the corresponding gene from Rhodobacter is discussed. The function
      of the different crtC and crtD genes in the pathway leading to the individual
      carotenoids is outlined. Since 1,1'-(HO)(2)-3,4-didehydrolycopene could not be
      produced in substantial amounts and 1-HO-3,4,3',4'-tetradehydrolycopene has not
      been described before, their structural characteristics were determined for the
      definite assignment of their identity. This included spectral properties,
      determination of relative molecular mass as well as the number of hydroxy groups
      by mass spectroscopy and NMR spectroscopy for 1,1'-(HO)(2)-3,4-didehydrolycopene.

PMID- 12052683
TI  - Reactive extraction of lactic acid using alamine 336 in MIBK: equilibria and
      kinetics.
AB  - Lactic acid is an important commercial product and extracting it out of aqueous
      solution is a growing requirement in fermentation based industries and recovery
      from waste streams. The design of an amine extraction process requires (i)
      equilibrium and (ii) kinetic data for the acid-amine (solvent) system used.
      Equilibria for lactic acid extraction by alamine 336 in methyl-iso-butyl-ketone
      (MIBK) as a diluent have been determined. The extent to which the organic phase
      (amine +MIBK) may be loaded with lactic acid is expressed as a loading ratio,
      z=[HL](o)/[B](i,o). Calculations based on the stoichiometry of the reactive
      extraction and the equilibria involved indicated that more lactic acid is
      transferred to the organic phase than would be expected from the (1:1)
      stoichiometry of the reaction. The extraction equilibrium was interpreted as a
      result of consecutive formation of two acid-amine species with stoichiometries of
      1:1 and 2:1. Equilibrium complexation constant for (1:1) and (2:1) has been
      estimated. Kinetics of extraction of lactic acid by alamine 336 in MIBK has also
      been determined. In a first study of its kind, the theory of extraction
      accompanied by a chemical reaction has been used to obtain the kinetics of
      extraction of lactic acid by alamine 336 in MIBK. The reaction between lactic
      acid and alamine 336 in MIBK in a stirred cell falls in Regime 3, extraction
      accompanied by a fast chemical reaction occurring in the diffusion film. The
      reaction has been found to be zero order in alamine 336 and first order in lactic
      acid with a rate constant of 1.38 s(-1). These data will be useful in the design
      of extraction processes.

PMID- 12052684
TI  - Expression of recombinant trichosanthin, a ribosome-inactivating protein, in
      transgenic tobacco.
AB  - Trichosanthin (TCS) is an antiviral plant defense protein, classified as a type-I
      ribosome-inactivating protein, found in the root tuber and leaves of the
      medicinal plant Trichosanthes kirilowii. It is processed from a larger precursor
      protein, containing a 23 amino acid amino (N)-terminal sequence (pre sequence)
      and a 19 amino acid carboxy (C)-terminal extension (pro sequence). Various
      constructs of the TCS gene were expressed in transgenic tobacco plants to
      determine the effects of the amino- and carboxy-coding gene sequences on TCS
      expression and host toxicity in plants. The maximum TCS expression levels of 2.7%
      of total soluble protein (0.05% of total dry weight) were obtained in transgenic
      tobacco plants carrying the complete prepro-TCS gene sequence under the
      Cauliflower mosaic virus 35S RNA promoter. The N-terminal sequence matched the
      native TCS sequence indicating that the T. kirilowii signal sequence was properly
      processed in tobacco and the protein translation inhibitory activity of purified
      rTCS was similar to native TCS. One hundred-fold lower expression levels and
      phenotypic aberrations were evident in plants expressing the gene constructs
      without the C-terminal coding sequence. Transgenic tobacco plants expressing
      recombinant TCS exhibited delayed symptoms of systemic infection following
      exposure to Cucumber mosaic virus and Tobacco mosaic virus (TMV). Local lesion
      assays using extracts from the infected transgenic plants indicated reduced
      levels of TMV compared with nontransgenic controls.

PMID- 12052686
TI  - Effects of dehydration temperature on water vapor adsorption and dissolution
      behavior of carbamazepine.
AB  - Anhydrous carbamazepine was prepared by heating carbamazepine dihydrate at 60,
      80, 100, 120, and 140 degrees C and used to investigate the effects of
      dehydration temperature on water vapor adsorption and dissolution behavior. The
      hydration rate of anhydrous carbamazepine at 75, 83, and 95% relative humidity
      and 25 degrees C decreased with increasing heating temperature. From the
      dissolution study by the rotating disk method, the calculated solubility of
      anhydrous carbamazepine was about 2.5 times higher than that of the dihydrate.
      The rate of phase transformation from the anhydrous form into the dihydrate
      during the dissolution process decreased with an increase in sample preparation
      temperature. These phenomena were further studied by thermal analysis, specific
      surface area measurement, density measurement, small-angle X-ray scattering, and
      wide-angle powder X-ray diffraction. As the heating temperature was raised, the
      specific surface area was reduced and the density was increased; furthermore, the
      average of the solid part calculated by the Debye method with small-angle X-ray
      scattering increased. The anhydrous carbamazepine prepared at lower heating
      temperatures was found to have a more porous structure and was seen by wide-angle
      powder X-ray diffraction to comprise both anhydrous forms I and II.

PMID- 12052685
TI  - Mass transfer correlations for rotating drum bioreactors.
AB  - Evaporative cooling is extremely important for large-scale operation of rotating
      drum bioreactors (RDBs). Outlet water vapour concentrations were measured for a
      RDB containing wet wheat bran with the aim of determining the mass transfer
      coefficient for evaporation from the bran bed to the headspace. Mass transfer was
      expressed as the mass transfer coefficient times the area for transfer per unit
      volume of void space in the drum. Values of ka' were determined under
      combinations of aeration superficial velocities ranging from 0.006 to 0.017 ms(
      1) and rotation rates ranging from 0 to 9 rpm. Mass transfer coefficients were
      evaluated using a variety of residence time distributions (RTDs) for flow in the
      gas phase including plug flow and well-mixed and a Central Jet RTD based on RTD
      studies. If plug flow is assumed, the degree of holdup at low effective Peclet
      (Pe(eff)) numbers gives an apparent under-estimate of ka' compared with empirical
      correlations. Values of ka' calculated using the Central Jet RTD agree well with
      values of ka' from literature correlations. There was a linear relationship
      between ka' and effective Peclet number: ka' = 2.32 x 10(-3)Pe(eff).

PMID- 12052687
TI  - Adsorption of an ionizable drug onto microspheres: experimental and modeling
      studies.
AB  - The purpose of this work was to study the in vitro equilibria and the adsorption
      kinetics of an ionizable drug, indomethacin, onto commercially available cationic
      polymeric microspheres: DEAE Trisacryl LS and QA Trisacryl LS. Isotherms were
      fitted to theoretical equations allowing accurate predictions of drug loading at
      different salt concentrations. Isotherm measurements were quickly obtained by
      simple column breakthrough experiments. The nature of the ion exchange group of
      the microspheres was observed to be preponderant for adsorption, as the tertiary
      amine derivative exhibited 53% more capacity than its quaternary amine
      counterpart. The maximum equilibrium uptake capacity in a 5 mM Tris-HCl buffer at
      pH 7.4 is 303 mmol/ml of particle volume, for DEAE microspheres. Transport
      properties of indomethacin into the tertiary amine microspheres were obtained in
      agitated contactor. Microbeads loading was completed in a 1-6 min range and was
      found to be controlled by pore diffusion mechanism. Equilibrium uptake data was
      fitted to the Langmuir and the mass action law models. Adsorption kinetics were
      fitted to a pore diffusion model. Good correlation was obtained between the
      theoretical models and the experimental data. The methodology outlined in this
      work provided a simple approach of estimating adsorption behavior of drugs onto
      ion-exchange macroporous microspheres. Although significant indomethacin loading
      was obtained onto the DEAE microspheres, the rapid rate of diffusion is not
      compatible with sustained release properties sought for this type of
      microspheres.

PMID- 12052688
TI  - On computational control of flow in airblast atomisers for pulmonary drug
      delivery.
AB  - Among different approaches to successful pharmacotherapy the pulmonary drug
      delivery (PDD) mode plays an increasingly important role. In this paper PDD
      systems based on air-blast atomisation have been analysed mathematically. In
      order to allow the bioengineer to estimate the degree of effectiveness of a
      specific system prototype and to lay the basic principles for design, a
      conservation-law-based mathematical model is discussed. Key control parameters
      that allow improvement in the efficiency of the system have been identified and
      main characteristics of the system have been analysed numerically as functions of
      these parameters.

PMID- 12052689
TI  - Role of poly [DL-lactide-co-glycolide] in development of a sustained oral
      delivery system for antitubercular drug(s).
AB  - An oral formulation based on poly (DL-lactide-co-glycolide) (PLG) microparticles
      was developed for delivery of antituberculous drugs. PLG entrapped antitubercular
      drugs when administered orally, were found to release the drugs in a sustained
      manner. This formulation was found to be stable in the acidic environment of
      gastric fluid whereas, in the intestinal fluid the drug release was obtained up
      to 20 days as indicated by in vitro studies. Pharmacokinetic analysis of the data
      revealed changes in C(max); AUC(o-alpha); t(1/2) (a) and t(1/2) (e) when drugs
      were given entrapped in PLG microparticles. Higher peak concentration, area under
      the concentration time curve and delayed elimination rate of entrapped drugs
      indicated the potential of PLG for effective treatment of tuberculosis. Further,
      work is being carried out to evaluate the chemotherapeutic efficacy of the
      antitubercular drugs encapsulated in PLG microspheres.

PMID- 12052690
TI  - Characterization of alginate/poly-L-lysine particles as antisense oligonucleotide
      carriers.
AB  - The gel forming characteristics of alginate in the presence of calcium ions and
      further crosslinking with poly-L-lysine led to the formation of sponge-like nano-
      and microparticles. The particle size was varied by adjusting the final
      concentrations of and proportions between the components. The region for particle
      formation was from 0.04 to 0.08% (w/v) of alginate in the final formulation, the
      change from the nm to microm size range occurred at a concentration of approx.
      0.055% (w/v). Oligonucleotide-loaded microparticles were prepared by two
      different methods, either by absorption of the drug into the crosslinked
      polymeric matrix or by incorporation of an oligonucleotide/poly-L-lysine complex
      into a calcium alginate pre-gel. The release of oligonucleotide from
      microparticles prepared by the first method was higher. The addition of
      increasing amounts of poly-L-lysine resulted in larger particles, higher
      oligonucleotide loading and slower drug release. An increase in the final solid
      content of the formulation led to larger particles, especially with high
      concentrated calcium alginate pre-gels. Microparticles based on alginate and poly
      L-lysine are potential carriers for antisense oligonucleotides.

PMID- 12052691
TI  - Release of ketoprofen enantiomers from HPMC K100M matrices--diffusion studies.
AB  - Sustained release formulations of ketoprofen elaborated with HPMC K100M were
      studied to test the hypothesis that chiral excipients can stereoselectively
      affect the release of the racemic drug. The differences observed in the
      percentage released between enantiomers show the existence of a chiral
      interaction between ketoprofen and HPMC K100M. HPMC interacts preferably with the
      S-enantiomer, although the enantioselectivity observed was not relevant from
      biopharmaceutical and clinical points of view. Diffusion studies were carried out
      in membrane diffusion cells to simplify the excipient-drug system and hence to
      analyze only the influence of diffusion process on the stereoselectivity. The
      results obtained show that the absence of the erosion process strengthens the
      enantiomeric differences observed in the drug release from tablets. Another
      objective of this work was to study the influence of formulation pH on the 'in
      vitro' release profile of ketoprofen. The amount and the release mechanism of
      ketoprofen from formulations elaborated are conditioned mainly by the pH of the
      matrix.

PMID- 12052692
TI  - Continuous twin screw extrusion for the wet granulation of lactose.
AB  - The suitability of continuous twin screw extrusion for the wet granulation of
      alpha-lactose monohydrate was studied and compared with conventional high shear
      granulation. The influence of process parameters (screw speed and total input
      rate) and formulation variables (water and polyvinylpyrrolidone (PVP)
      concentration) on the properties of granules (yield, particle size distribution,
      friability and compressibility) and tablets (tablet tensile strength, friability
      and disintegration time) was investigated. Variation of the formulation and
      process parameters had a major effect on the process feasibility. Optimization of
      these parameters is required to allow continuous processing and to ensure a high
      yield. Total input rate, screw speed and water concentration had a minor
      influence on the granule and the tablet properties. The addition of PVP had no
      major influence on the granule properties, but significantly affected the tablet
      characteristics. For granules formulated with and without PVP a yield above 50%,
      a friability below 30% and a compressibility below 15% was obtained. Tablets
      without PVP showed a tensile strength below 0.6 MPa, a friability above 1% and a
      disintegration time below 3 min, whereas tablets with PVP showed a tensile
      strength above 0.6 MPa, a friability below 1% and a disintegration time ranging
      from 8 to 15 min. High shear granulation was only possible when PVP was added and
      it required a higher amount of water. It was concluded that wet granulation of
      alpha-lactose monohydrate using continuous twin screw extrusion is a robust
      process and might offer a suitable alternative for high shear granulation in the
      pharmaceutical industry.

PMID- 12052693
TI  - Preparation of alginate beads for floating drug delivery system: effects of CO(2)
      gas-forming agents.
AB  - Floating beads were prepared from a sodium alginate solution containing CaCO(3)
      or NaHCO(3) as gas-forming agents. The solution was dropped to 1% CaCl(2)
      solution containing 10% acetic acid for CO(2) gas and gel formation. The effects
      of gas-forming agents on bead size and floating properties were investigated. As
      gas-forming agents increased, the size and floating properties increased. Bead
      porosity and volume average pore size, as well as the surface and cross-sectional
      morphology of the beads were examined with Mercury porosimetry and Scanning
      Electron Microscopy. NaHCO(3) significantly increased porosity and pore diameter
      than CaCO(3). Incorporation of CaCO(3) into alginate solution resulted in
      smoother beads than those produced with NaHCO(3). Gel strength analysis indicated
      that bead strength decreased with increasing gas-forming agent from 9 to 4 N.
      Beads incorporating CaCO(3) exhibited significantly increased gel strength over
      control and NaHCO(3)-containing samples. Release characteristics of riboflavin as
      a model drug were studied in vitro. Release rate of riboflavin increased
      proportionally with addition of NaHCO(3). However, increasing weight ratios of
      CaCO(3) did not appreciably accelerate drug release. The results of these studies
      indicate that CaCO(3) is superior to NaHCO(3) as a gas forming agent in alginate
      bead preparations. The enhanced buoyancy and sustained release properties of
      CaCO(3)-containing beads make them an excellent candidate for floating drug
      dosage systems (FDDS).

PMID- 12052694
TI  - A local delivery system for fentanyl based on biodegradable poly(L-lactide-co
      glycolide) oligomer.
AB  - To obtain a sustained fentanyl delivery with effective and precise control,
      fentanyl loaded wafer was fabricated using poly(L-lactide-co-glycolide) (PLGA)
      oligomer by direct compression method. XRD and DSC analysis indicated the
      presence of crystalline drug in the wafers. The release of fentanyl from PLGA
      wafer was determined to be primarily diffusion controlled, but swelling and
      erosion also contributed to the release process. In vitro release studies showed
      that different release patterns and rates could be achieved by simply modifying
      factors in the preparation conditions. The wafer degradation profiles were also
      investigated to understand the drug release mechanism. Gravimetric studies of
      mass loss of wafers during the incubation revealed that the weight loss increased
      apparently after 4 days. These results indicate that the polymer degradation was
      contributed to drug release followed by diffusion. From the results, this
      constant localized release system can potentially provide anesthesia for a longer
      period than injection or topical administration.

PMID- 12052695
TI  - Utilization of supercritical carbon dioxide for complex formation of ibuprofen
      and methyl-beta-cyclodextrin.
AB  - The dissolution rate of a drug into the biological environment can be enhanced by
      forming complexes with cyclodextrins and their derivatives. In this study,
      ibuprofen-methyl-beta-cyclodextrin complexes were prepared successfully by
      passing ibuprofen-laden CO(2) through a methyl-beta-cyclodextrin packed bed. The
      maximum drug loading obtained in this work was 10.8 wt.%, which was comparable to
      that of a 1:1 complex (13.6 wt.% of ibuprofen). The complex exhibited
      instantaneous dissolution profiles in water solution. The enhanced dissolution
      rate was attributed to the amorphous character and improved wettability of the
      product.

PMID- 12052696
TI  - Investigation of polymeric nanoparticles as carriers of enalaprilat for oral
      administration.
AB  - Enalaprilat is a typical angiotensin-converting enzyme inhibitor and is very
      poorly absorbed from the gastrointestinal tract. The aim of this study was to
      design and characterize poly-(lactide-co-glycolide) (PLGA) and
      polymethylmethacrylate (PMMA) nanoparticles containing enalaprilat and to
      evaluate the potential of these colloidal carriers for the transport of drugs
      through the intestinal mucosa. Nanoparticle dispersions were prepared by the
      emulsification-diffusion method and characterized according to particle size,
      zeta potential, entrapment efficiency and physical stability. Effective
      permeabilities through rat jejunum of enalaprilat in solution and in enalaprilat
      loaded nanoparticles were compared using side-by-side diffusion chambers. The
      solubility of enalaprilat is very low in many acceptable organic solvents, but in
      benzyl alcohol is sufficient to enable the production of nanoparticles by the
      emulsification-diffusion process. The diameters of drug-loaded PMMA and PLGA
      nanoparticles were 297 and 204 nm, respectively. The concentration of the
      stabilizer polyvinyl alcohol (PVA) in dispersion has an influence on particle
      size but not on drug entrapment. The type of polymer has a decisive influence on
      drug content--7 and 13% for PMMA and PLGA nanoparticles, respectively. In vitro
      release studies show a biphasic release of enalaprilat from nanoparticle
      dispersions-fast in the first step and very slow in the second. The apparent
      permeability coefficient across rat jejunum of enalaprilat entrapped in PLGA
      nanoparticles is not significantly improved compared with enalaprilat in
      solution.

PMID- 12052697
TI  - Preparation of solid lipid nanoparticles with clobetasol propionate by a novel
      solvent diffusion method in aqueous system and physicochemical characterization.
AB  - Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled
      drug delivery. Monostearin SLN were prepared by a novel solvent diffusion method
      in an acidic aqueous system in order to improve the recovery of the method. The
      lipophilic model drug clobetasol propionate was incorporated to study the
      recovery of nanoparticles, entrapment efficacy, zeta potential (charge) and drug
      delivery characterization. The drug and monostearin were dissolved in acetone and
      ethanol at 50 degrees C in water bath, the resultant organic solution was poured
      into an acidic aqueous (pH 1.10) containing 1% polyvinyl alcohol (PVA) under
      mechanical agitation at room temperature. The drug loaded SLN was quickly
      produced with an aggregation state and easily separated by centrifugation. The
      recovery of nanoparticles was markedly increased compared to using a usual
      aqueous (pH 5.73) containing the same concentration of PVA. After burst drug
      release at the first 3 h, a distinctly prolonged release over a monitored period
      of 4 days was observed and nearly 6% drug was released in each day. Further, a
      novel preparation method and the optimized separation parameters in the present
      research for SLN were established. These results also demonstrate the principle
      suitability of SLN as a prolonged release formulation for lipophilic drugs.

PMID- 12052698
TI  - Estimation of intradermal disposition kinetics of drugs: II. Factors determining
      penetration of drugs from viable skin to muscular layer.
AB  - To develop a more efficient transdermal delivery system, it is very important to
      regulate the intradermal disposition of drugs after topical application. We tried
      to elucidate the factors determining the intradermal disposition kinetics,
      especially drug penetration from the viable skin to the muscular layer, mainly
      based on the six-compartment model, including the contralateral skin and muscle
      for ten model drugs with different physicochemical characteristics. In vivo
      transdermal absorption study was performed for six model drugs using the stripped
      skin rats. The fitting analyses by the six-compartment model gave the theoretical
      curves describing the observed data very well and the reasonable pharmacokinetic
      parameters, showing the pharmacokinetic model should be useful for the estimation
      of the intradermal disposition kinetics of drugs applied topically again. The
      simulation study using the pharmacokinetic parameters obtained above could show
      the relative contribution of the direct penetration and the distribution from the
      systemic circulation to the muscular distribution of drugs. The largest
      contribution of direct penetration was observed for antipyrine (90.8%) and the
      smallest was for felbinac (43.3%). Among the pharmacokinetic parameters obtained
      above, the clearance from the viable skin to the muscle (CL(vs-m)) was found to
      be significantly correlated with the unbound fraction of drugs in the viable skin
      (fu(vs)). Although the clearance from the viable skin to the plasma (CL(vs-p))
      also tended to increase as fu(vs) increased, the ratio of CL(vs-m) to CL(vs-p)
      was significantly correlated with fu(vs), meaning that the larger amount of
      unbound drug in the viable skin significantly contributes to the direct
      penetration into the muscle more than to the systemic absorption. On the other
      hand, k(direct) values obtained in in vitro penetration study-the penetration
      rate constant of drugs from the viable skin to the muscular layer-were found to
      be correlated with CL(vs-m) values for seven model drugs. Therefore, adding the
      in vitro experiments for the other three model drugs, the multiple linear
      regression analysis of k(direct) was performed for ten model drugs in terms of
      fu(vs), logarithm of the partition coefficient (Log P) and molecular weight. The
      results clearly showed the largest and significant contribution of fu(vs) to the
      direct penetration of drugs from the viable skin to the muscular layer,
      indicating that a drug with the higher value of fu(vs) in the viable skin can
      penetrate more into the muscular layer.

PMID- 12052699
TI  - Characterisation of the mechanical properties of polymer films formed from
      aqueous polymer dispersions by creep testing.
AB  - The mechanical properties of films formed from an aqueous dispersion of
      polymethlymethacrylate (Eudragit NE30D) and as mixture with an aqueous dispersion
      of ethylcellulose (Aquacoat ECD30), have been assessed by applying creep tests at
      different temperatures, using a dynamic mechanical analyser. In the region of
      linear creep, the film prepared from 100% Eudragit was far less elastic than when
      60% Aquacoat was present. In this region, when the applied stress was doubled,
      the strain response was doubled. In the non-linear region of behaviour, there is
      clear evidence that the mixed film is more elastic than the film containing only
      Eudragit.

PMID- 12052700
TI  - Clickhaler dry powder inhaler: focussed in vitro proof of principle evaluation of
      a new chemical entity for asthma.
AB  - A new chemical entity (NCE) was evaluated in the Clickhaler (Innovata Biomed
      Ltd.) dry powder inhaler, a reservoir-based multidose delivery system. The
      standard device metering system was modified to handle higher doses (nominally 20
      mm(3) of lactose based blend). The micronized drug was formulated at 12.5% w/w in
      lactose monohydrate (Pharmatose 325M, DMV) equivalent to a nominal dose of
      approximately 1 mg. Delivered shot weight (mg of blend) and emitted dose (microg
      drug) averaged 7.4 mg and 905 microg, respectively, and were consistent (within
      +/-20 to 25% of mean) through the life of the inhaler. The fine particle fraction
      (FPF) (Andersen cascade impactor) was typically 60%. A short stability study
      (i.e. 3 months at room temperature, 53 or 75% RH, unpacked) showed that the in
      vitro performance was maintained. The results of these studies provide in vitro
      proof of principle for this novel drug/device combination.

PMID- 12052701
TI  - Modelling partitioning of sparingly soluble drugs in a two-phase liquid system.
AB  - The aim of this work was to develop a proper mathematical model able to describe
      the kinetics partitioning of a drug between a polar (water buffer) and an apolar
      (n-octanol) liquid phase. In particular, attention is focussed on sparingly
      soluble drugs in one or both environments. Basically, we suppose that drug fluxes
      occurring between the polar and apolar phase depend also on drug solubility, and
      not only on both the kinetics constants and the instantaneous drug concentration
      in the two phases. The proposed model adequately describes the drug partitioning
      of sparingly water soluble drugs (piroxicam and nimesulide) as proven by the
      comparison of the predicted and experimental data. Moreover, it indicates the
      unsuitability of a previous approach (Chem. Pharm. Bull. 29 (1961) 2718) in
      describing the partitioning kinetics unless sink conditions in both phases are
      attained, this being difficult to achieve when working with sparingly soluble
      drugs. Consequently, the model represents a simple and reliable tool to study the
      drug partitioning kinetics.

PMID- 12052702
TI  - The influence of pellet shape and surface properties on the drug release from
      uncoated and coated pellets.
AB  - Pellets of different shape, varying from spherical to cylindrical, without and
      with film coating were tested for their drug release properties. For non
      disintegrating uncoated pellets, drug release was found to be inversely related
      to the pellet porosity. A change of 5% in porosity doubled the value of the mean
      dissolution time (MDT). As coat thickness increased, the MDT value of coated
      pellets increased. For those pellets, which are nearly spherical, once a
      thickness of about 20 microm had been achieved, there was little further
      reduction in retardation. Pellets produced by extrusion/spheronisation appeared
      to prolong drug release to a larger extent than those where the extrusion step
      had been omitted. There was a strong inverse relationship between the surface
      area by volume of the coated pellets and the value of the MDT. The values of the
      relative dispersion coefficient (RD), which is an indicator of the drug release
      mechanism, were related to the amount of fluid used to manufacture the pellets
      and the pellet shape, in a similar fashion for both uncoated and coated pellets.
      This suggested that the presence of the film coating changed the rate but not the
      mechanism of drug release.

PMID- 12052703
TI  - Kinetic examination of the mechanical transition of polymethyl methacrylate films
      prepared from aqueous dispersions.
AB  - The activation energy of the phase transition of cast polymethyl methacrylate
      films produced from an aqueous dispersion (Eudragit NE30D) has been estimated
      from Dynamic Mechanical Thermal Analysis. The value was found to lie between 170
      and 350 kJ mol(-1), the variation arising from the different specimen test
      geometry and testing conditions. From experiments conducted at a range of
      frequencies and temperatures it was found possible to utilise the concept of
      frequency shift to produce a master curve, which could relate viscoelastic
      properties over the temperature range of 5-55 degrees C and a frequency range of
      0.1 to 50 Hz.

PMID- 12052704
TI  - Optimized chemical structure of nanoparticles as carriers for oral delivery of
      salmon calcitonin.
AB  - Nanoparticles having two kinds of surface hydrophilic polymeric chains were
      prepared by the free radical copolymerization between styrene and hydrophilic
      macromonomers terminating in vinylbenzyl groups. Their potential as carriers for
      oral peptide delivery was investigated using salmon calcitonin (sCT) in rats.
      After oral administration of mixtures of sCT and nanoparticles, the ionized
      calcium concentration in blood was measured. The absorption of sCT was
      significantly enhanced by nanoparticles having poly-N-isopropylacrylamide
      (PNIPAAm) chains on their surfaces. This enhancement effect was considerably
      increased by introducing cationic poly-vinylamine (PVAm) groups to the surface of
      PNIPAAm nanoparticles. The absorption enhancement depended on the ratio of NIPAAm
      and VAm macromonomers to styrene in the nanoparticle preparation. In contrast,
      the introduction of nonionic poly-vinylacetamide (PNVA) groups eliminated
      completely the absorption-enhancing function of PNIPAAm nanoparticles. It was
      suggested that this disappearance was due to the shielding of PNIPAAm groups by
      PNVA groups. The enhancement effect of sCT absorption by nanoparticles was
      greatly dominated by their chemical structure that was closely related to surface
      characteristics. Optimization of the chemical structure on the basis of the
      mechanism of the absorption enhancement resulted in the further improvement of
      sCT absorption.

PMID- 12052705
TI  - An in vitro evaluation of a chitosan-containing multiparticulate system for
      macromolecule delivery to the colon.
AB  - A multiparticulate system of chitosan hydrogel beads has been investigated for
      colon-specific delivery of macromolecules using fluorescein isothiocyanate
      labeled bovine serum albumin as a model protein. The hydrogel bead was formed by
      polyelectrolyte complexation of chitosan with its counterion, tripolyphosphate
      (TPP). The protein release experiments were carried out in vitro under different
      conditions to simulate the pH and times likely to be encountered during
      intestinal transit to the colon. The results show that the hydrogel beads were
      degraded by rat cecal and colonic enzymes, resulting in a marked acceleration in
      the release of protein. The ability of rat cecal and colonic enzymes to degrade
      chitosan hydrogel beads was independent of pretreatment conditions. A commercial
      beta-glucosidase preparation containing a chitinase did not have a similar effect
      on the chitosan bead, even though it has been found to mimic the degradation
      function of rat cecal and colonic enzymes in vitro for chitosan in solution.
      Degradation of the chitosan-TPP hydrogel beads in the presence of rat cecal and
      colonic enzymes indicates the potential of this multiparticulate system to serve
      as a carrier to deliver macromolecules specifically to the colon.

PMID- 12052706
TI  - Preformulation studies of a novel camptothecin anticancer agent, CKD-602:
      physicochemical characterization and hydrolytic equilibrium kinetics.
AB  - (20S)-7-(2-isopropylamino)ethylcamptothecin.HCl (CKD-602), a new camptothecin
      (CPT) anticancer agent, is a pale yellowish crystalline compound. DSC thermogram
      exhibited a melt endotherm near 270 degrees C, and CKD-602 was found to be
      slightly hygroscopic. The solubility of CKD-602 in deionized water was 8.22
      mg/ml, and two pK(a) values were measured to be 2.32 and 9.15, respectively. A pH
      dependent partition coefficient behavior in octanol-buffer was observed. CKD-602
      in solid state was stable over the range of temperature and humidity, but
      decomposed slightly by light. The hydrolysis of CKD-602 occurred reversibly and
      rapidly in aqueous buffer solutions. The conversion rate constants (k(f): from
      the lactone to the carboxylate and k(r): from the carboxylate to the lactone) and
      the final equilibrium ratio (K(eq)) between two species were dependent on the pH
      of aqueous solutions.

PMID- 12052707
TI  - Introduction and overview of peptide and protein pegylation.

PMID- 12052708
TI  - The origin of pegnology.

PMID- 12052709
TI  - Chemistry for peptide and protein PEGylation.
AB  - Poly(ethylene glycol) (PEG) is a highly investigated polymer for the covalent
      modification of biological macromolecules and surfaces for many pharmaceutical
      and biotechnical applications. In the modification of biological macromolecules,
      peptides and proteins are of extreme importance. Reasons for PEGylation (i.e. the
      covalent attachment of PEG) of peptides and proteins are numerous and include
      shielding of antigenic and immunogenic epitopes, shielding receptor-mediated
      uptake by the reticuloendothelial system (RES), and preventing recognition and
      degradation by proteolytic enzymes. PEG conjugation also increases the apparent
      size of the polypeptide, thus reducing the renal filtration and altering
      biodistribution. An important aspect of PEGylation is the incorporation of
      various PEG functional groups that are used to attach the PEG to the peptide or
      protein. In this paper, we review PEG chemistry and methods of preparation with a
      particular focus on new (second-generation) PEG derivatives, reversible
      conjugation and PEG structures.

PMID- 12052710
TI  - Mono-N-terminal poly(ethylene glycol)-protein conjugates.
AB  - A site-directed method of joining proteins to poly(ethylene glycol) is presented
      which allows for the preparation of essentially homogeneous PEG-protein
      derivatives with a single PEG chain conjugated to the amine terminus of the
      protein. This selectivity is achieved by conducting the reductive alkylation of
      proteins with PEG-aldehydes at lower pH. Working examples demonstrating the
      application of this method to improve the delivery characteristics and
      therapeutic value of several proteins are provided.

PMID- 12052711
TI  - Enzymatic procedure for site-specific pegylation of proteins.
AB  - We have developed a novel methodology for site-specific pegylation of proteins by
      use of transglutaminase (TGase). In this methodology, alkylamine derivatives of
      poly(ethyleneglycol) (PEG) could be site-specifically incorporated into intact or
      chimeric proteins without decreasing the bioactivities. The incorporation site of
      the TGase-catalyzed modification is limited to the substrate Gln residues for
      TGases. The high homogeneity of the constructed conjugates and the ability to
      design conjugates with suitable incorporation sites will improve the
      applicability of PEG-protein conjugates for clinical use.

PMID- 12052712
TI  - Effects of PEG conjugation on insulin properties.
AB  - The goal of this research was to determine whether the site-specific attachment
      of poly(ethylene glycol) to insulin could enhance the physical and
      pharmacological properties of insulin without negatively affecting its biological
      activity or immunological properties. Electrophilically activated derivatives of
      low-molecular-weight monomethoxypoly(ethylene glycol) (mPEG) were chemically
      coupled to insulin via its amino groups at positions phenylalanine-B1 or lysine
      B29, with an amide bond being formed between the polymer and protein. The site
      specific attachment of mPEG to insulin did not substantially alter insulin's
      secondary/tertiary structure, self-association behavior, or potency in vivo.
      However, mPEG attachment did significantly enhance insulin's resistance to
      aggregation. In addition, the pegylation of insulin almost completely eliminates
      the resultant conjugate's immunogenicity, allergenicity, and antigenicity.
      Finally, the conjugates were observed to remain in the systemic circulation for
      longer periods of time than unmodified insulin after subcutaneous administration.

PMID- 12052713
TI  - PEGylated antibodies and antibody fragments for improved therapy: a review.
AB  - The use of covalent attachment of poly(ethylene glycol) to various different
      proteins in order to modify their function has been reported over many years. One
      class of protein that this technology has more recently been applied to is
      antibodies and antibody fragments. PEG has been predominantly used to reduce the
      immunogenicity and increase the circulating half-lives of antibodies. It may also
      have a beneficial effect on the use of antibodies in certain clinical settings
      such as tumour targeting. This review describes previously reported experience
      with PEGylated antibodies and antibody fragments, and where these types of
      molecules may find clinical usefulness in the future.

PMID- 12052714
TI  - Structural and biological characterization of pegylated recombinant interferon
      alpha-2b and its therapeutic implications.
AB  - The type I interferon alpha family consists of small proteins that have
      clinically important anti-infective and anti-tumor activity. Interferon alpha-2b
      (Intron A) combination therapy with ribavirin is the current standard of care for
      the treatment of chronic hepatitis C virus infection. A drawback to the therapy
      however, is the short serum half-life and rapid clearance of the interferon alpha
      protein. Schering-Plough has developed a semi-synthetic form of Intron A by
      attaching a 12-kDa mono-methoxy polyethylene glycol to the protein (PEG Intron)
      which fulfills the requirements of a long-acting interferon alpha protein while
      providing significant clinical benefits. A detailed physicochemical and
      biological characterization of PEG Intron revealed its composition of pegylated
      positional isomers and the specific anti-viral activity associated with each of
      them. Though pegylation appeared to decrease the specific activity of the
      interferon alpha-2b protein, the potency of PEG Intron, independent of protein
      concentration, was comparable to the Intron A standard at both the molecular and
      cellular level. Importantly, PEG Intron has demonstrated an enhanced
      pharmacokinetic profile in both animal and human studies. Recently, PEG Intron in
      combination with ribavirin has been shown to be very effective in reducing
      hepatitis C viral load and maintaining effective sustained viral suppression in
      patients. Because of the improved clinical benefits, it is anticipated that the
      PEG Intron plus ribavirin combination therapy will become the new standard of
      care for the treatment of chronic hepatitis C.

PMID- 12052715
TI  - Use of peginterferon alfa-2a (40 KD) (Pegasys) for the treatment of hepatitis C.
AB  - Thrice-weekly interferon alfa-2b plus ribavirin has been the standard of care for
      chronic hepatitis C; however, a majority of patients fail to achieve a sustained
      virological response with this treatment. Peginterferon alfa-2a (40 KD),
      interferon alfa-2a conjugated to a 40 kDa branched polyethylene glycol moiety,
      exhibits sustained absorption and reduced renal clearance, resulting in antiviral
      pressure throughout a once-weekly dosing schedule. Peginterferon alfa-2a (40 KD)
      has superior virological efficacy to interferon alfa-2a, and elicits histological
      improvements in patients with and without sustained virological response.
      Peginterferon alfa-2a (40 KD) is effective in patients infected with viral
      genotype 1 and those with liver cirrhosis. Viral RNA measurements at 12 weeks can
      be used to predict the probability of achieving sustained virological response to
      peginterferon alfa-2a (40 KD) therapy. Peginterferon alfa-2a (40 KD) has
      comparable safety to interferon alfa-2a. The addition of ribavirin to
      peginterferon alfa-2a (40 KD) further enhances the therapeutic benefit for
      patients with hepatitis C.

PMID- 12052716
TI  - Polyethylene glycol-superoxide dismutase, a conjugate in search of exploitation.
AB  - Without a doubt PEG-SOD has been the enzyme most studied in PEGylation. One can
      say that it represents the preferred model to assess chemistries for PEG
      activation, analytical procedures suitable for conjugate characterization, the
      influence of PEG size in conjugate removal from circulation and elimination of
      immunogenicity and antigenicity, and the effect of route of administration. The
      effect of PEG conjugation was studied in vitro and in vivo models in comparison
      with the free enzyme and the following conclusions may be drawn: (1) At the blood
      vessel level, PEG-SOD has been shown to provide a greater resistance to oxidant
      stress, to improve endothelium relaxation and inhibit lipid oxidation. (2) In the
      heart, PEG-SOD proved to be at least as effective as native SOD in treatment of
      reperfusion-induced arrhythmias and myocardial ischemia. (3) In the lung, PEG-SOD
      appeared to be able to reduce oxygen toxicity and E. coli-induced lung injury,
      but not in the treatment of lung physiopathology associated with endotoxin
      induced acute respiratory failure and in the reduction of asbestos-induced cell
      damage. (4) On cerebral ischemia/reperfusion injuries the effect of PEG-SOD was
      uncertain, also due to the difficulty of cerebral cell penetration. (5) In kidney
      and liver ischemia both enzyme forms were found to ameliorate reperfusion damage.
      In view of so much positive research on PEG-SOD, it is surprising that no
      approved application in human therapy has been established and approved.

PMID- 12052717
TI  - Rational combinatorial chemistry-based selection, synthesis and evaluation of an
      affinity adsorbent for recombinant human clotting factor VII.
AB  - The selection, synthesis and chromatographic evaluation of a synthetic affinity
      adsorbent for human recombinant factor VIIa is described. The requirement for a
      metal ion-dependent immunoadsorbent step in the purification of the recombinant
      human clotting factor, FVIIa, has been obviated by using the X-ray
      crystallographic structure of the complex of tissue factor (TF) and Factor VIIa
      and has directed our combinatorial approach to select, synthesise and evaluate a
      rationally-selected affinity adsorbent from a limited library of putative
      ligands. The selected and optimised ligand comprises a triazine scaffold bis
      substituted with 3-aminobenzoic acid and has been shown to bind selectively to
      FVIIa in a Ca(2+)-dependent manner. The adsorbent purifies FVIIa to almost
      identical purity (>99%), yield (99%), activation/degradation profile and impurity
      content (approximately 1000 ppm) as the current immunoadsorption process, while
      displaying a 10-fold higher static capacity and substantially higher reusability
      and durability.

PMID- 12052718
TI  - Determination of free and total (free plus protein-bound) melatonin in plasma and
      cerebrospinal fluid by high-performance liquid chromatography with fluorescence
      detection.
AB  - A simple, sensitive and accurate method for the estimation of free and total
      (free plus protein-bound) melatonin (MLT) in human plasma and cerebrospinal fluid
      (CSF) is described. Via Chem-Elut cartridges, free and total MLT (the latter
      obtained after a deproteinization step) were quantified in dichloromethane
      extracted samples and analyzed in one chromatographic run by high-performance
      liquid chromatography (HPLC) with fluorimetric detection. The column used was an
      Extrasil ODS-2 (3 microm, 150 x 4.6 mm I.D.), while the mobile phase consisted of
      75 mM sodium acetate-acetonitrile (72:28, v/v) (pH 5.0). Repeatability and
      reproducibility of the method were 3.24 and 9.4%, respectively. The recovery of
      melatonin from plasma and CSF was 99.9+/-4.0% for non-deproteinized samples and
      93.2+/-4.8% for deproteinized samples. The detection limit of the assay was 0.5
      pg/ml. In human plasma, the mean+/-SD concentrations in the darkness period were
      23.18+/-7.44 pg/ml for free melatonin and 82.5+/-36.48 pg/ml for total melatonin,
      while the lowest concentrations detected during daytime were 2.23+/-2.22 and
      7.40+/-5.68 pg/ml, respectively. Detection of MLT in CSF was 5.01+/-2.31 and
      28.55+/-6.95 pg/ml for the free and total fraction, respectively.

PMID- 12052720
TI  - Sensitive liquid chromatographic method using fluorescence detection for the
      determination of estradiol 3- and 17-glucuronides in rat and human liver
      microsomal incubations: formation kinetics.
AB  - We have developed a sensitive and specific HPLC-fluorescence assay for the
      determination of estradiol-3-glucuronide and estradiol-17-glucuronide in human
      and rat liver microsomal incubations. The method utilizes a mobile phase
      comprised of acetonitrile and 50 mM ammonium phosphate buffer (35:65, v/v) that
      is pumped though a phenyl column at 1 ml/min; the run time is less than 15 min.
      Calibration curves for both metabolites were linear over the range 20-4000 pmol.
      The intra- and inter-day coefficients of variation were <6%. In both rat and
      human liver microsomes, the formation of estradiol-3-glucuronide displayed
      atypical kinetics (consistent with activation), while estradiol-17-glucuronide
      formation was consistent with classical Michaelis-Menten kinetics. Overall, the
      assay described is a sensitive and reproducible method for the determination of
      estradiol glucuronides in liver microsomal preparations.

PMID- 12052719
TI  - Characterization of deoxyribonuclease I immobilized on magnetic hydrophilic
      polymer particles.
AB  - Magnetic bead cellulose particles and magnetic poly(HEMA-co-EDMA) microspheres
      with immobilized DNase I were used for degradation of chromosomal and plasmid
      DNAs. Magnetic bead particles were prepared from viscose and magnetite powder.
      Magnetic poly(HEMA-co-EDMA) microspheres were prepared by dispersion
      copolymerization of 2-hydroxyethyl methacrylate and ethylene dimethacrylate in
      the presence of magnetite. Divalent cations (Mg(2+), Ca(2+), Mn(2+) and Co(2+))
      were used for the activation of DNase I. A comparison of free and immobilized
      enzyme (magnetic bead particles) activities was carried out in dependence on pH
      and activating cation. The maximum of the activity of immobilized DNase I was
      shifted to lower pH compared with free DNase I. DNase I immobilized on magnetic
      bead cellulose was used 20 times in the degradation of chromosomal DNA. Its
      residual activity was influenced by the nature of activating divalent cation. The
      immobilized enzyme with decreased activity was reactivated by Co(2+) ions.

PMID- 12052721
TI  - Identification of incurred sulfonamide residues in eggs: methods for confirmation
      by liquid chromatography-tandem mass spectrometry and quantitation by liquid
      chromatography with ultraviolet detection.
AB  - Two complementary methods for identifying and measuring sulfonamide residues in
      eggs were developed for use in surveying eggs for potential drug residues. The
      first method uses liquid chromatography-tandem mass spectrometry (LC-MS-MS) to
      confirm the presence of sulfonamide residues in eggs. During its validation the
      limit of confirmation was estimated to be 5-10 ng/g (ppb) depending on the drug.
      Also, a method for measuring residue level by liquid chromatography with
      ultraviolet detection (LC-UV) was validated using the same extraction procedure
      as the confirmatory method. The determinative method was validated over the 50
      200 ppb range. Samples were prepared by homogenizing whole egg, extracting with
      acetonitrile, and cleaning up with a C(18) solid-phase extraction cartridge. For
      confirmation, analytes were separated by gradient LC on a C(18) column, ionized
      by electrospray ionization (ESI), and detected by MS-MS with an ion trap mass
      spectrometer. For determination, analytes were separated by a different gradient
      LC procedure and detected by UV at 287 nm. Fifteen drugs were dosed individually
      in laying hens, and residues of parent drug and/or metabolites were found in eggs
      for all the drugs. Validation was based on repetitive analyses of control
      samples, control samples fortified at 100 ppb sulfonamides, and samples of
      blended incurred eggs.

PMID- 12052722
TI  - Three-dimensional protein map according to pI, hydrophobicity and molecular mass.
AB  - A three-dimensional method has been developed to map the protein content of cells
      according to pI, M(w) and hydrophobicity. The separation of complex protein
      mixtures from cells is performed using isoelectric focusing (IEF) in the liquid
      phase in the first dimension, non-porous silica (NPS) RP-HPLC in the second
      dimension and on-line electrospray ionization (ESI) time-of-flight mass
      spectrometry (TOF-MS) detection in the third dimension. The experimentally
      determined pI, M(w) and hydrophobicity can then be used to produce a three
      dimensional map of the protein expression of a cell, where now each protein can
      be tagged by three independent parameters. The ESI-TOF-MS provides an accurate
      M(w) for the intact protein while the hydrophobicity dimension results from the
      RP-HPLC component of the separation. The elution time, or percent acetonitrile at
      time of elution, of the protein is related to the hyrophobicity, which is an
      inherent property of the protein. 3D protein maps can thus be generated showing
      pI, M(w) and % acetonitrile at time of elution as well as pI, M(w) and
      hydrophobicity. The potential of the 3D plot for effective mapping of proteins
      from cells compared to current 2D methods is discussed.

PMID- 12052723
TI  - Identification of ractopamine residues in tissue and urine samples at ultra-trace
      level using liquid chromatography-positive electrospray tandem mass spectrometry.
AB  - Beta-agonist compounds are widely used in human therapeutics because of
      bronchodilator or heart tonic properties; they are also used as growth promoters
      in food-producing animals. Ractopamine is a forbidden molecule in the EU, but is
      registered as an additive in other countries such as in the USA for pigs.
      Consequently, efficient analytical methods were developed to survey residues in
      edible tissue and urine samples. This paper describes a protocol based on a
      powerful extraction and purification process and a liquid chromatography-positive
      electrospray mass spectrometry identification method. A validation was performed
      according to the "DG SANCO 1805/2000" European decision. The obtained decision
      limit (CCalpha) and detection capability (CCbeta) were as low as 10 and 30 ng/kg
      (ppt), respectively. This method appeared very efficient on incurred samples,
      including porcine edible tissues (meat, liver, kidney), tissues enriched in beta
      agonist receptors (lung, retina), and finally bovine urine samples.

PMID- 12052724
TI  - Determination of ketoconazole in human plasma by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - A simple, rapid and specific high-performance liquid chromatography coupled with
      tandem mass spectrometry (LC-MS-MS) has been developed and validated for the
      determination of ketoconazole in human plasma. The method used diethyl ether to
      extract the ketoconazole and the internal standard (I.S.) R51012 from alkalinized
      plasma sample. The LC separation was on a C(18) column (50 x 3 mm, 5 microm)
      using acetonitrile-water-formic acid (75:25:1, v/v/v) mobile phase. The retention
      times were approximately 1.8 min for both ketoconazole and the I.S. The MS-MS
      detection was by monitoring 531.2-->82.1 (m/z) for ketoconazole, and 733.5-
      >460.2 (m/z) for the I.S. The dynamic range was from 20.0 to 10000 ng/ml based on
      0.1 ml plasma, with linear correlation coefficient of > or =0.9985. The run time
      was 2.5 min/injection. The recoveries of ketoconazole and the I.S. were 102 and
      106%, respectively. The precision and accuracy of the control samples were with
      the relative standard deviations (RSDs) of < or =4.4% (n=6) and the relative
      errors (REs) from -0.6 to 1.4% for intra-day assay, and < or =8.6% RSD (n=18) and
      -1.4 to 0.9% RE for inter-day assay. The partial volume tests demonstrated good
      dilution integrity. Three freeze-thaw cycles, keeping plasma samples at ambient
      for 24 h, storing extracted samples at ambient for 24 h, and storing frozen
      plasma samples at approximately -20 degrees C for up to 2 months did not show
      substantial effects.

PMID- 12052725
TI  - Simple and rapid quantification of the non-nucleoside reverse transcriptase
      inhibitors nevirapine, delavirdine, and efavirenz in human blood plasma using
      high-performance liquid chromatography with ultraviolet absorbance detection.
AB  - A simple reversed-phase high-performance liquid chromatography assay for the
      simultaneous quantitative determination of three HIV non-nucleoside reverse
      transcriptase inhibitors (nevirapine, delavirdine, and efavirenz) in human blood
      plasma is described. The method was validated over the range of 10 ng/ml to 50
      microg/ml for nevirapine, 25 ng/ml to 25 microg/ml for delavirdine, and 10 ng/ml
      to 10 microg/ml for efavirenz. The method is accurate (average accuracies over
      eight concentrations ranging from 87.3 to 113%), and precise (within-day and
      between-day precision measures ranging from 0.12 to 7.9% and 0.26 to 5.9%,
      respectively). All three non-nucleoside reverse transcriptase inhibitors proved
      to be stable under various conditions. Due to its simplicity, this assay can
      readily be used for investigational or clinical monitoring of plasma
      concentrations.

PMID- 12052726
TI  - Chromatographic approach for determining the relative membrane permeability of
      drugs.
AB  - With the aid of the experimental dependence of the theoretical plate height (H)
      on the flow-rate (U), values of diffusion coefficients as the permeation rate, of
      the compounds in a polymeric stationary phase were calculated from solute mass
      transfer. This approach is proposed for modeling the relative diffusion rate of a
      drug within the membrane. After the successful separation of opioid compounds
      using a C(18) derivatized polystyrene-divinylbenzene polymer HPLC column, the
      slopes of H-U plots increase quantitatively in the order of
      meperidine<alfentanil<fentanyl<sufentanil, indicating that the large mass
      transfer resistance slows down the penetration of molecules. A constant intercept
      for the experimental plate height supports the proposal interpretation. A good
      correlation between the diffusion coefficients and hydrophobicity (log P(oct))
      from the traditional shake-flask method was obtained for the opioid compounds,
      demonstrating that the more lipophilic molecules penetrate deeper into the
      stationary phase leading to a lower migration rate under the specified
      conditions. Plot of the diffusion coefficients versus potency ratio for different
      opioids after intravenous administration reflect the values of the dynamic
      process in drug studies. The work herein differs from existing studies by
      measuring the permeability of drugs into the stationary phase rather than
      providing membrane partition coefficients for a series of analogues. Thus, the
      study of drug permeability combined with other physico-chemical properties, such
      as hydrophobicity, may provide additional information on drug-membrane
      interactions.

PMID- 12052727
TI  - High-resolution microanalysis of nitrite and nitrate in neuronal tissues by
      capillary electrophoresis with conductivity detection.
AB  - Nitrites and nitrates are widely used reporters of endogenous activity of nitric
      oxide synthases (NOS), an important group of enzymes producing the gaseous signal
      molecule nitric oxide (NO). However, due to the great chemical heterogeneity of
      neuronal tissues, standard analytical protocols for evaluation of neuronal
      nitrite/nitrate concentrations are inefficient. We optimized a high-performance
      capillary zone electrophoresis (CZE) technique to analyze nitrite/nitrate
      concentrations in submicroliter samples from mammalian neuronal tissues. The
      measurements were made using a PrinCE 476 computerized capillary electrophoresis
      system with a Crystal 1000 contact conductivity detector. Isotachophoretic
      stacking injection of 1000- to 10000-fold diluted samples, which had been
      pretreated with a custom-designed solid-phase microextraction (SPME) cartridge,
      was employed to assay micromolar and nanomolar nitrite and nitrate levels in the
      presence of the high millimolar chloride concentrations characteristic of many
      biological samples. In the presented technique, a 10-microl volume of diluted
      ganglionic sample was used for chloride removal and sample cleanup. The method
      yields high analytical performance, including good reproducibility, resolution,
      and accuracy. The limits of detection relative to undiluted sample matrix were
      8.9 nM (0.41 ppb) and 3.54 nM (0.22 ppb) for nitrite and nitrate, respectively.
      In addition, this technique resolves other anions that are present in neuronal
      tissues at sub-nanomolar concentrations and can be broadly applied for high
      throughput anionic profiling. In rat dorsal root ganglia, endogenous levels of
      nitrate (231+/-29 microM; n=6) and nitrite (24-96 microM) were found. These
      concentrations exceeded those previously found in neuronal tissue homogenates
      using different techniques.

PMID- 12052728
TI  - High-performance liquid chromatographic assay for amiodarone N-deethylation
      activity in human liver microsomes using solid-phase extraction.
AB  - A selective and sensitive assay for amiodarone N-deethylation activity in human
      liver microsomes by high-performance liquid chromatography (HPLC) with UV
      detection is reported. The extraction of desethylamiodarone from incubation
      samples was performed by means of an original solid-phase extraction (SPE)
      procedure using a polymeric reversed-phase sorbent (Oasis HLB). The method was
      validated for the determination of desethylamiodarone with respect to
      specificity, linearity, precision, accuracy, recovery, limit of quantitation and
      stability. Amiodarone N-deethylation activity from low to high substrate
      concentrations using human liver microsomes was precisely determined without a
      concentration step. This method is applicable to the study in vitro of the
      metabolism of amiodarone.

PMID- 12052729
TI  - Separation and identification of phosphatidylserine molecular species using
      reversed-phase high-performance liquid chromatography with evaporative light
      scattering and mass spectrometric detection.
AB  - A reversed-phase HPLC method compatible with evaporative light scattering (ELS)
      and electrospray mass spectrometric (ES-MS) detection was developed for
      separation of phosphatidylserine (PS) molecular species. The method was optimised
      for separation of three disaturated synthetic species: dipalmitoyl
      glycerophosphoserine, palmitoyl-stearoyl glycerophosphoserine and distearoyl
      glycerophosphoserine using isocratic elution with a mixture of 2-propanol,
      tetrahydrofuran and ammonium formate. Baseline separation was obtained on three
      different columns: one polystyrene/divinylbenzene (PS/DVB) column and two silica
      based C(18) and C(30) columns. The best chromatographic resolution was achieved
      with the C(30) column. The limit of detection for DPPS was 5 microg/ml (S/N=3)
      with ELS detection and 0.1 microg/ml (S/N=3) with negative ion ES-MS in the
      single ion monitoring mode. Baseline separation of the five main species in a
      biological PS sample, bovine brain PS, was obtained with the PS/DVB column.
      Species identification was done by using the retention times of the intact PS
      species and their corresponding carboxylate anion fragments obtained by in-source
      fragmentation. Data have shown that individual PS species can be identified by
      their retention times using direct ELS detection in a mixture of disaturated PS
      species. However, for the bovine brain PS electrospray-MS detection was necessary
      for species identification due to the many possible fatty acid combinations in
      biological PS.

PMID- 12052747
TI  - Editorial commentary on scientific fraud.

PMID- 12052730
TI  - Direct amperometric determination of lactate at a carbon fiber bundle microdisk
      electrode by capillary zone electrophoresis.
AB  - Capillary zone electrophoresis was employed for the determination of lactate
      using end-column amperometric detection at a carbon fiber bundle microdisk
      electrode. The optimum conditions of separation and detection are 3.6 x 10(-3)
      mol/l Na(2)HPO(4)-1.4 x 10(-3) mol/l NaH(2)PO (pH 7.2) for the buffer solution,
      18 kV for the separation voltage and 1.60 V versus the saturated calomel
      electrode for the detection potential. The limit of detection is 7.6 x 10(-7)
      mol/l or 1.7 fmol (S/N=3) and the linear range is 1.7 x 10(-6)-8.2 x 10(-4) mol/l
      for the injection voltage of 6 kV and injection time of 5 s. The RSD is 1.8% for
      the migration time and 3.3% for the electrophoretic peak current. The method was
      applied to the determination of lactate in human saliva. The recovery of the
      method is between 95 and 109%.

PMID- 12052748
TI  - Scientific data from clinical trials: investigators' responsibilities and rights.

PMID- 12052749
TI  - Should a potentially noncurative resection that prolongs survival be offered to
      patients with colorectal liver metastases?

PMID- 12052750
TI  - Screening colonoscopy for family history of colorectal cancer: a growing
      consensus.

PMID- 12052751
TI  - The results of the Department of Defense's breast lymphatic mapping study.

PMID- 12052752
TI  - Significance of hepatic pedicle lymph node involvement in patients with
      colorectal liver metastases: a prospective study.
AB  - BACKGROUND: We investigated whether hepatic pedicle lymph node (HP-LN)
      involvement is a more significant prognostic factor and whether HP-LN dissection
      could be efficient in patients with positive HP-LN involvement. METHODS: From
      1988 to 1998, HP-LN dissection was prospectively performed in 160 patients
      undergoing hepatectomy for colorectal liver metastases. Survival of patients with
      HP-LN involvement limited to the hepatoduodenal ligament and retropancreatic
      portion (area 1) was compared with that of patients with HP-LN involvement
      spreading over the common hepatic artery and celiac axis (area 2). RESULTS: HP-LN
      involvement was detected in 17 patients. The survival rate was significantly
      lower in patients with HP-LN involvement. HP-LN involvement was the most
      significant prognostic factor. Survival was significantly higher in patients with
      HP-LN involvement limited to area 1 than in those with HP-LN involvement
      spreading over area 2. CONCLUSIONS: HP-LN involvement was the most significant
      prognostic indicator in patients with colorectal liver metastases. Positive LNs
      of area 1 should no longer be considered an absolute contraindication to liver
      resection, but in case of area 2 lymph node involvement, liver resection does not
      seem justified.

PMID- 12052753
TI  - Colonoscopy in asymptomatic individuals with a family history of colorectal
      cancer.
AB  - BACKGROUND: This study was performed to evaluate the use of total colonoscopy as
      the optimal screening test in asymptomatic individuals with a family history of
      colorectal cancer (CRC). METHODS: Colonoscopy was performed in 249 asymptomatic
      individuals who had one or two first-degree relatives (FDRs) with CRC;
      individuals with three or more FDRs with CRC were excluded. RESULTS: Eighty-six
      colonic lesions were found in 51 individuals (51 of 249; 20.5%). Among these 51
      subjects, 27 had neoplastic polyps (n = 38) and 29 had metaplastic polyps (n =
      44). Although no invasive cancer was detected, in 14 individuals the lesions had
      a high malignancy potential because of their size and histopathology. We did not
      confirm a statistically significant difference in the incidence of neoplastic
      polyps according to the number of affected FDRs. Finally, the presence of
      metaplastic polyps was a very strong indication for the concomitant presence of
      metaplastic polyps (P <.0001). CONCLUSIONS: Total colonoscopy is the optimal
      screening procedure for the examination of asymptomatic individuals with a family
      history of CRC.

PMID- 12052754
TI  - Preoperative chemoradiation in patients with resectable rectal cancer: results on
      tumor response.
AB  - BACKGROUND: There is no consensus about the role of preoperative radiotherapy
      (RT) and chemotherapy (CT) in patients with resectable cancer of the distal
      rectum. This study analyzed the local clinical and pathologic response in
      patients receiving preoperative RT/CT for rectal cancer. METHODS: Thirty-two
      consecutive patients with a palpable adenocarcinoma of the rectum received
      preoperative RT (45 Gy in 25 fractions over 5 weeks) plus continuous chemotherapy
      with doxifluridine and leucovorin or 5-fluorouracil by continuous intravenous
      infusion during RT. Surgery was performed 8 weeks later. The Wilcoxon and chi(2)
      tests were used for data analysis. RESULTS: Twelve patients had mild
      gastrointestinal toxicity, only one of whom required interruption of therapy. The
      tumor shrank to 57.8% of its original size, and at the echoendoscopy (u) there
      was a 58.7% decrease of the maximum diameter (P <.001). Downstaging from uT3 and
      uT2 to <uT3 and <uT2, respectively, occurred in 41.6% of patients (P =.0020).
      Total and major regression of the tumor at the histopathologic examination
      occurred in 12.5% and 50% of patients. CONCLUSIONS: Local response to
      preoperative RT/CT was highly satisfactory and allowed conservative surgery in
      81% of patients. Optimization of the combined therapy could achieve even better
      results.

PMID- 12052755
TI  - The expression of murine double minute 2 is a favorable prognostic marker in
      esophageal squamous cell carcinoma without p53 protein accumulation.
AB  - BACKGROUND: Murine double minute 2 (MDM2) is an oncoprotein that inhibits the
      function of p53 tumor-suppressor protein. Although there have been a few reports
      on MDM2 gene abnormalities, there has been no investigation into expression of
      the product of this gene in esophageal squamous cell carcinoma. Thus, the
      clinicopathological and prognostic significance of the product of the MDM2 gene
      is as yet unknown. METHODS: MDM2 protein expression status was analyzed in
      surgically resected materials by immunohistochemical procedures. RESULTS: The
      expression of MDM2 significantly correlated inversely with tumor size, depth of
      invasion, lymph node metastasis, lymphatic vessel invasion, and stage of disease.
      However, the expression of MDM2 correlated with neither p53 protein accumulation
      status nor Ki-67 labeling index. The prognosis with MDM2-positive status was
      significantly better than that with MDM2-negative status for patients with p53
      negative tumors, but not in those with p53-positive tumors. Moreover,
      multivariate analysis showed that the expression of MDM2 was an independent
      prognostic factor in patients with p53-negative tumors. CONCLUSIONS: These
      findings indicate that MDM2 immunohistochemical analysis may provide useful
      information concerning the prognosis in esophageal squamous cell carcinoma
      patients with p53-negative tumors.

PMID- 12052756
TI  - Magnetic resonance imaging-guided biopsy of mammographically and clinically
      occult breast lesions.
AB  - BACKGROUND: Breast magnetic resonance imaging (MRI) is a very sensitive technique
      for detection of breast cancer. We report on MRI-guided needle localization for
      biopsy of abnormalities seen only on MRI. METHODS: A retrospective review was
      performed of 231 patients with invasive breast cancer or ductal carcinoma-in-situ
      who had MRI as part of their evaluation and treatment at the University of
      Pennsylvania between 1992 and 1998. Clinical, radiological, and pathologic data
      were examined. RESULTS: MRI needle localization was performed in 41 (18%)
      patients. MRI needle localization was required for a finding of a
      mammographically or clinically occult lesion in 31 patients, better MRI
      definition of tumor in 5 patients, and surgeon's choice in 5 patients. In all
      cases, MRI localization and excisional biopsy were successfully completed.
      Nineteen of 31 patients were found to have additional mammographically and
      clinically occult tumors. There were 12 (29%) false-positive MRI scans.
      CONCLUSIONS: MRI has a high sensitivity for detection of breast cancer;
      additional mammographically and clinically occult sites of tumor are detected in
      approximately 1 (15%) of 7 breast cancer patients. These otherwise occult sites
      of disease can be appropriately biopsied with MRI needle-localization techniques.

PMID- 12052757
TI  - Skin-sparing mastectomy and immediate breast reconstruction: a prospective cohort
      study for the treatment of advanced stages of breast carcinoma.
AB  - BACKGROUND: Recent published series demonstrate the safety and effectiveness of
      skin-sparing mastectomy (SSM) with immediate reconstruction for the treatment of
      early-stage breast carcinoma. Although several reports have retrospectively
      evaluated outcomes after breast reconstruction for locally advanced disease
      (stages IIB and III), no study has specifically considered immediate breast
      reconstruction after SSM for locally advanced disease. METHODS: From 1996 to
      1998, 67 consecutive patients with breast carcinoma underwent SSM with immediate
      reconstruction and were prospectively observed. From this group of patients,
      those with locally advanced disease (stage IIB, n = 12; stage III, n = 13) were
      analyzed separately. Tumor characteristics, adjuvant therapy, type of
      reconstruction, operative time, complications, hospital stay, and incidence of
      local recurrence and distant metastasis were noted. RESULTS: Breast
      reconstruction consisted of a transverse rectus abdominis myocutaneous flap (n =
      22) or a latissimus flap plus an implant (n = 4). The median operative time was
      5.5 hours; the average hospital stay was 5.2 days. Complications required
      reoperation in three patients (12%): partial skin flap necrosis in two and
      partial abdominal skin necrosis in one. Surgery on the opposite breast for
      symmetry was required in one patient (4%). Postoperative adjuvant therapy was not
      significantly delayed (median interval, 32 days). With a median length of follow
      up of 49.2 months (range, 33-64 months), local recurrence was present in only one
      patient (4%), with successful local salvage treatment, and distant metastasis was
      present in four patients (16%). CONCLUSIONS: SSM with immediate reconstruction
      seems safe and effective and has a low morbidity for patients with advanced
      stages of breast carcinoma. Local recurrence rates and the incidence of distant
      metastasis are not increased compared with those of patients who have had
      modified radical mastectomies without reconstruction.

PMID- 12052758
TI  - Biology of lymphatic metastases in breast cancer: lessons learned from sentinel
      node biopsy.
AB  - BACKGROUND: The evolution of sentinel node biopsy has placed new emphasis on the
      biology of lymphatic metastases in breast cancer. If radiocolloid mimics the
      migration of tumor cells, the nodes with the most uptake should also be the most
      likely to harbor metastatic cells. We attempted to correlate the frequency of
      metastatic disease to the greatest gamma uptake and to clarify the physiology of
      breast lymphatic drainage. METHODS: Data were collected from 152 patients
      undergoing sentinel node biopsy from January 1997 to June 1999. Localization was
      by injection of unfiltered (99m)Tc-labeled sulfur colloid. Sentinel nodes were
      identified with an intraoperative gamma counter and the 10% rule. A completion
      level I/II axillary dissection was performed in all patients. RESULTS: Fifty-four
      of 152 patients were positive for metastatic disease. There were no false
      negative sentinel nodes. In 46 (85%) of 54 cases, the node with the highest
      uptake was positive for metastatic disease. In the remaining eight (15%) cases,
      another node with a lower gamma count was positive. CONCLUSIONS: The sentinel
      node with the highest uptake is not the one that contains metastatic disease in
      15% of cases. This may reflect variations in lymphatic channels or technical
      variations in colloid properties and injection technique.

PMID- 12052759
TI  - Gold standard for sternectomies and plastic reconstructions after resections for
      primary or secondary sternal neoplasms.
AB  - BACKGROUND: Between January 1980 and December 1999, 88 patients underwent the
      surgical resection of sternal tumors: 30 primary malignant tumors, 28 local
      relapses or metastases from breast carcinomas, 16 other types of tumor, and 14
      radionecroses. METHODS: The sternectomies were total in 8 cases, subtotal in 32,
      and partial in 48. Prosthetic materials covered by flaps of myocutaneous or
      muscle tissue were used in 55 patients, prosthetic material alone in 13,
      myocutaneous or muscle flaps alone in 5, and other techniques in the remaining
      15. The resection was radical in 78 cases and palliative in the other 10.
      RESULTS: Forty-eight of the subjects who underwent radical surgery were alive and
      disease free at the end of the follow-up period. The expected 10-year survival of
      the patients treated for primary tumors is approximately 85% (Kaplan-Meier), and
      that of the patients with relapsing breast carcinomas is the same as after 5
      years (41.8%). CONCLUSIONS: In our experience, the treatment of neoplasms by
      means of a broad sternal resection followed by a reconstruction based on the use
      of prosthetic materials is an effective and safe solution that considerably
      improves the quality of life and makes it possible to perform curative broad
      radical resections in the case of primary sternal resections.

PMID- 12052760
TI  - Laparoscopic resection of large adrenal tumors.
AB  - BACKGROUND: The maximum size of adrenal tumors that should be removed with a
      laparoscopic approach is controversial. It has been suggested that laparoscopic
      adrenalectomy is appropriate only for adrenal tumors < 6 cm in size. We report
      our experience with laparoscopic adrenalectomy in patients with adrenal tumors of
      > or =6 cm compared with patients with smaller tumors. METHODS: We
      retrospectively reviewed a consecutive series of patients who had a laparoscopic
      adrenalectomy. Patients were considered candidates for laparoscopic adrenalectomy
      if their computed tomography (CT) scan showed a well-encapsulated tumor confined
      to the adrenal gland. RESULTS: Sixty laparoscopic adrenalectomies were performed
      in 53 patients. Twelve of the adrenalectomies (20%) were for tumors that were >
      or =6 cm (median, 8 cm; range, 6 to 12 cm). There have been no local or regional
      recurrences, but one patient with adrenocortical carcinoma developed pulmonary
      metastases. When the 12 patients with large tumors were compared with the 36
      patients with tumors < 6 cm, the median operative time (190 vs. 180 minutes; P
      =.32), operative blood loss (100 vs. 50 mL; P =.53), and postoperative hospital
      stay (2 vs. 2 days; P = 1.0) were similar. CONCLUSIONS: The size of an adrenal
      tumor should not be the primary factor in determining whether a laparoscopic
      adrenalectomy should be performed. Large adrenal tumors that are confined to the
      adrenal gland on CT can be removed with a laparoscopic approach.

PMID- 12052761
TI  - Active immunotherapy by reinduction with a polyvalent allogeneic cell vaccine
      correlates with improved survival in recurrent metastatic melanoma.
AB  - BACKGROUND: We have observed prolonged survival in patients undergoing vaccine
      reinduction after resection of recurrent metastatic melanoma and adjuvant
      polyvalent allogenic cell vaccine (PACV) immunotherapy. We hypothesized that
      reinduction with a more intensive vaccine regimen would re-stimulate specific
      immune responses that were correlated with survival after recurrence. METHODS:
      From 1996 to 1998, 194 patients developed recurrence during adjuvant PACV
      (CancerVax vaccine) treatment after resection of metastatic melanoma. Recurrent
      disease was treated with or without vaccine reinduction. Reinduction regimen
      entailed an increased vaccine frequency and coadministration of two doses of
      bacille Calmette-Guerin (BCG). PACV Delayed-type hypersensitivity (DTH) responses
      were prospectively recorded. Survival was defined as the interval from recurrence
      to death. RESULTS: Ninety-four patients underwent reinduction immunotherapy. DTH
      responses to PACV before recurrence increased significantly after reinduction
      therapy (P =.0001). The median survival time was 37 months for reinduced patients
      and 17 months for other patients. On multivariate analysis, reinduction status
      remained a significant prognostic variable (P =.0277). In the reinduction group,
      there was a significant correlation between PACV DTH responses and survival (P
      =.0178). CONCLUSIONS: Reinduction vaccine regimen can enhance immune responses in
      previously immunized patients and is associated with prolonged survival after
      recurrence in patients receiving the same active specific immunotherapy.

PMID- 12052762
TI  - Selective use of preoperative venous duplex ultrasound and intraoperative
      venography for central venous access device placement in cancer patients.
AB  - BACKGROUND: Central venous access in cancer patients is often challenging. A
      history of access is common. Appropriate indications for venous imaging studies
      are not clearly defined. METHODS: This study was a retrospective analysis of
      selective use of preoperative venous duplex ultrasound and intraoperative
      venography in 248 consecutive cancer patients undergoing central venous access
      placement. RESULTS: Ninety patients had a history of central venous access
      placement. Eleven had a history of deep venous thrombosis of an upper extremity
      or central vein. One hundred three underwent preoperative ultrasound. Previous
      central venous access placement was not associated with an abnormal preoperative
      ultrasound; however, previous central venous access with deep venous thrombosis
      was (P =.014). Thirty patients underwent intraoperative venography, of which 18
      also had preoperative ultrasound. Fifty percent of patients with an abnormal
      intraoperative venogram had no abnormal findings on preoperative ultrasound.
      CONCLUSIONS: Routine preoperative ultrasound is unnecessary. We advocate the
      selective use of preoperative ultrasound in those with a history of central
      venous access associated with deep venous thrombosis. We advocate the use of
      intraoperative venography when there is difficulty advancing the guidewire or
      catheter or when preoperative ultrasound is negative despite a history of central
      venous access with deep venous thrombosis.

PMID- 12052763
TI  - Combined gene therapy and ionizing radiation is a novel approach to treat human
      esophageal adenocarcinoma.
AB  - BACKGROUND: The ability to infect tumor cells limits the antitumor effects of
      gene therapy. The addition of radiotherapy to treatment with Ad.Egr.TNF.11D, a
      replication-deficient adenovirus containing a radiation-inducible promoter, early
      growth response-1, and the tumor necrosis factor-alpha (TNFalpha) complementary
      DNA may enhance the therapeutic ratio. METHODS: Seg-1 human esophageal
      adenocarcinoma cells were treated with Ad.Egr.TNF.11D with or without radiation.
      TNFalpha levels were quantified with enzyme-linked immunosorbent assay. Athymic
      nude mice bearing Seg-1 tumors were randomized to buffer, ionizing radiation,
      Ad.Egr.TNF.11D, and combination therapy. Tumor growth delay was used to compare
      treatment regimens. TNFalpha levels were measured in tumor homogenates and
      plasma. RESULTS: Seg-1 cells treated with Ad.Egr.TNF.11D and ionizing radiation
      demonstrated increased TNFalpha levels at 72 hours compared with cells exposed to
      vector alone (124 +/- 0 pg/mL vs. 31.11 +/- 22 pg/mL; P =.008). In vivo,
      Ad.Egr.TNF.11D-treated tumors expressed low TNFalpha levels (151.5 +/- 107.11
      pg/mg protein) compared with tumors receiving combined treatment (793.92 +/-
      489.13 pg/mg protein; P =.067). Increased TNFalpha levels were associated with
      increased tumor growth delay after combined treatment (P <.05). CONCLUSIONS:
      Radiotherapy enables focal stimulation of TNFalpha expression in Ad.Egr.TNF.11D
      infected cells and thus improves local tumor control.

PMID- 12052765
TI  - An NIH/NSF for Europe?

PMID- 12052764
TI  - Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa
      of colon resections from colon cancer patients.
AB  - BACKGROUND: Abnormal areas in normal-appearing flat colonic mucosa (field
      defects) may predispose individuals to colon cancer. Markers of field defects
      would indicate cancer risk. METHODS: We evaluated apoptosis capability,
      dedifferentiation, frequency of simple aberrant crypts, aberrant crypt foci,
      microadenomas, and total nicotinamide adenine dinucleotide levels at locations
      within normal-appearing flat mucosa obtained from colon resections. RESULTS:
      Among goblet cells from colonic mucosa samples of individuals without colonic
      neoplasia, there was a high mean deoxycholate-induced apoptotic index (AI) of
      59.1% and high Dolichos biflorus agglutinin (DBA) lectin reactivity
      (differentiation) in 85.0% of samples. In contrast, flat mucosa samples from
      colon cancer patients had a significantly (P <.01) lower average AI of 37.4%, and
      a significantly (P =.03) lower percentage (40.5%) had high DBA reactivity. For
      colon cancer patients, AI and DBA reactivity values were patchy within a
      resection. Nicotinamide adenine dinucleotide levels were highly variable among
      individuals without neoplasia, and aberrant crypt foci and microadenomas were
      rare. CONCLUSIONS: AI and aberrant DBA reactivity are promising indicators of
      colon cancer risk. Our results attest to the importance of obtaining multiple
      samples to assess colon cancer risk because of the patchy nature of field
      defects.

PMID- 12052766
TI  - Coding or non-coding, that is the question: having solved the last technical
      hurdles to extract DNA information from virtually any biological material,
      forensic biologists now have to ponder the ethical and social questions of using
      information from exonic DNA.

PMID- 12052767
TI  - What to call human cloning: the technical terminology increasingly used in the
      cloning debate sidesteps the ethical questions raised.

PMID- 12052768
TI  - A day at the museum: science centres and museums play an increasingly important
      role in bringing science and technology to the public.

PMID- 12052769
TI  - Virtual rice: Japan sets up the Rice Simulator Project to create an in silico
      rice plant.

PMID- 12052772
TI  - Disease models for every field: workshop on the molecular basis of human
      congenital lymphocyte disorders.

PMID- 12052773
TI  - Peptidyl-prolyl isomerases: a new twist to transcription.
AB  - Peptidyl-prolyl isomerases (PPIs) catalyse the cis-trans isomerisation of peptide
      bonds N-terminal to proline residues in polypeptide chains. They have roles in
      the folding of newly synthesised proteins and in the function of the immune
      system. In addition, members of the parvulin-like family of PPIs have been
      implicated in cell cycle control. Their activity is directed by the prior
      phosphorylation of target proteins in both yeast and mammalian cells. More recent
      data have illustrated that they may also influence other nuclear events. This
      review examines PPI activity in the context of eukaryotic transcriptional
      regulation. The findings are consistent with a two-step model of conformational
      control, in which the outcome depends on the transcription factor involved.

PMID- 12052774
TI  - Merging mitochondria matters: cellular role and molecular machinery of
      mitochondrial fusion.
AB  - Fusion is essential for mitochondrial function in a great variety of eukaryotic
      cell types. Yeast cells defective in mitohondrial fusion are respiration
      deficient, human cells use complementation of fused mitochondria as a defence
      against the accumulation of oxidative damage during cellular aging and fusion is
      required to build an intracellular mitochondrial continuum that allows the
      dissipation of energy in the cell. Moreover, developmental processes such as
      spermatogenesis in Drosophila require regulated mitochondrial fusion. Some of the
      molecular mediators of mitochondrial membrane fusion have been identified in
      recent years. An evolutionarily conserved large GTPase in the outer membrane is
      essential for mitochondrial fusion, and genetic screens in yeast are revealing an
      increasing number of additional important genes. Mechanistic studies have
      provided the first insights into how the problem of faithfully fusing a double
      membrane-bounded organelle in a coordinated manner is solved.

PMID- 12052775
TI  - NurA, a novel 5'-3' nuclease gene linked to rad50 and mre11 homologs of
      thermophilic Archaea.
AB  - We isolated and characterized a new nuclease (NurA) exhibiting both single
      stranded endonuclease activity and 5'-3' exonuclease activity on single-stranded
      and double-stranded DNA from the hyperthermophilic archaeon Sulfolobus
      acidocaldarius. Nuclease homologs are detected in all thermophilic archaea and,
      in most species, the nurA gene is organized in an operon-like structure with
      rad50 and mre11 archaeal homologs. This nuclease might thus act in concert with
      Rad50 and Mre11 proteins in archaeal recombination/repair. To our knowledge, this
      is the first report of a 5'-3' nuclease potentially associated with Rad50 and
      Mre11-like proteins that may lead to the processing of double-stranded breaks in
      3' single-stranded tails.

PMID- 12052776
TI  - The creation of a database of odorous compounds focused on molecular rigidity and
      analysis of the molecular features of the compounds in the database.
AB  - It is important to select odorous molecules for experiments on olfaction and for
      the development of an electronic nose. Odorous molecules having a small number of
      conformers, namely structurally rigid molecules, are assumed to interact with a
      small number of types of olfactory receptor proteins or to interact with the
      proteins in a simpler manner than that of fairly flexible molecules. Focusing on
      the rigidity of molecular structures, we collected 287 odorous molecules from
      data sources, which included 1205 chemicals in total and a database of the 287
      odorous molecules (DB_odMOL) was created using CS ChemFinder Pro (version 5.0).
      The logarithmic value of the octanol/water partition coefficient (log P) and
      melting point, boiling point and vapour pressure of the molecules were estimated
      using CS Chem3D Pro. The database DB_odMOL accumulates these estimated data in
      addition to literature values for odour quality, odour detection thresholds and
      the safety of molecules. The rigidity of the 287 molecules was further analysed
      by conformational analysis performed by molecular mechanics using Conformer in CS
      Chem3D Pro (version 5) and 72 rigid odorous molecules were selected. The 287
      molecules were also analysed based on atomic composition, substructure and
      molecular size. Sixty-two odorous molecules among the 72 rigid odorous molecules
      were further selected based on their atomic composition. The 62 rigid molecules
      with simple atomic composition that were finally selected should be useful for
      researchers in choosing odorous molecules for the study of olfaction, including
      the fields of molecular biology, physiology, structure-odour relationships and
      other fields of the study concerning odour.

PMID- 12052777
TI  - Ratings of different olfactory judgements in schizophrenia.
AB  - We assessed the influence of schizophrenia on different olfactory tasks. Forty
      patients with schizophrenia (20 males and 20 females) and 40 control subjects (20
      males and 20 females) were tested. The experiment included two sessions.
      Initially, 12 odorants were presented at a rate of one per minute. The subjects
      were asked to rate intensity, pleasantness, familiarity and edibility for each
      odour using linear rating scales. The odorants were then presented a second time
      and the subjects were asked to identify them. The results showed that the scores
      for pleasantness, familiarity, edibility and identification but not intensity
      were disturbed in patients when compared with control subjects. Furthermore, the
      familiarity judgement of male patients was more often deficient than that of
      female patients and they rated odorants as being inedible when the women judged
      them as neutral. Considered together, these data show that our olfactory test may
      be used in patients with schizophrenia for evidencing various dysfunctions
      specific to different types of olfactory processing that represent steps in the
      odour name identification process.

PMID- 12052778
TI  - Are polyamines involved in olfaction? An EAG and biochemical study in Periplaneta
      americana antennae.
AB  - Polyamines have been implicated in modulation of numerous cell functions. The
      purpose of this study was to assess the role of polyamines in intracellular
      regulation of insect antenna. Analysis of study data showed two main findings.
      First, in vivo treatment with the polyamine synthesis inhibitor alpha
      difluoromethyl-ornithine enhanced the sensitivity of male Periplaneta americana
      antenna to female pheromonal blend. Secondly, polyamine modulated phosphorylation
      of several antennary proteins including two found exclusively in antenna (30 and
      48 kDa). In both of these exclusive antennary proteins, phosphorylation changed
      after stimulation with the pheromonal blend. These results suggest that
      polyamines play a regulatory role in detection of female pheromonal blend and
      that modulation of protein phosphorylation is one of the mechanisms involved in
      this regulation.

PMID- 12052779
TI  - Sensory detection of glutaraldehyde in drinking water-emergence of sensitivity
      and specific anosmia.
AB  - A study of 30 young adults (15 males, 15 females), screened to have normal
      olfaction, measured detection of the flavor of glutaraldehyde, a biocide that
      could occur in disinfected potable water. Over the range of interest, up to 100
      p.p.m., flavor derived from olfactory stimulation. Higher concentrations would
      cause oral irritation. Fourteen subjects failed to detect the glutaraldehyde in
      the first of four sessions of testing. Eight of the 14 (seven males, one female)
      continued to exhibit the anosmia throughout testing. The other six (one male,
      five females) began to detect the material in session two and exhibited
      increasing sensitivity over sessions two to four. Their average sensitivity never
      reached that of the 16 subjects who evinced no anosmia and who also improved
      their performance over sessions. The combined group of 22 could detect 17 p.p.m.
      Less thorough testing would have yielded much higher values. Specific anosmia for
      this dialdehyde has precedence in anosmia for various monoaldehydes, most notably
      isobutyraldehyde. The positive influence of experience with a material on
      detection has been found previously, most intriguingly by Wysocki and colleagues,
      who showed that experience could differentially induce sensitivity to the odorant
      androstenone and suggested that the phenomenon might occur for other compounds.
      Glutaraldehyde appears to be one, perhaps of many.

PMID- 12052780
TI  - Activation and inhibition of the transduction process in silkmoth olfactory
      receptor neurons.
AB  - Electrophysiological responses of olfactory receptor neurons in both male and
      female silkmoths (Bombyx mori) were investigated. In both sexes, the G-protein
      activator sodium fluoride and 1,2-dioctanoyl-sn-glycerol, a membrane-permeable
      analog of the protein kinase C activator diacylglycerol, elicited nerve impulse
      responses similar to those elicited by weak continuous stimulation with odorants.
      Therefore, G(q)-proteins and diacylglycerol-activated ion channels seem to be
      involved in the transduction process in both pheromone-sensitive neurons in males
      and general odorant-sensitive neurons in females. Decyl-thio-trifluoro-propanone
      is known to inhibit electrophysiological responses of male moths to pheromones,
      but has no effect in females. Application of this inhibitor reduced the
      frequency, but not the amplitude of elementary receptor potentials. It had no
      inhibitory effect on nerve impulse responses elicited by sodium fluoride or 1,2
      dioctanoyl-sn-glycerol. This supports the idea that decyl-thio-trifluoro
      propanone acts on a prior step of the transduction cascade, e.g. on the pheromone
      receptor molecules. General odorants, such as (+/-)-linalool and 1-heptanol,
      excite olfactory receptor neurons in females, but inhibit the pheromone-sensitive
      neurons in males. Both (+/-)-linalool and 1-heptanol inhibited the responses of
      male neurons elicited by sodium fluoride or 1,2-dioctanoyl-sn-glycerol. (+/-)
      Linalool reduced the amplitude of elementary receptor potentials. In contrast to
      decyl-thio-trifluoro-propanone, (+/-)-linalool and 1-heptanol seem to interfere
      with later processes of the transduction cascade, possibly the opening of ion
      channels.

PMID- 12052781
TI  - The neural differentiation gene Mash-1 has a distinct pattern of expression from
      the taste reception-related genes gustducin and T1R2 in the taste buds.
AB  - Taste bud cells have a limited lifespan and are continuously replaced just like
      other epithelial cells. Although there is some evidence that taste buds may arise
      from the local epithelium, taste receptor cells have neuronal properties. This
      implies that there must be a critical stage at which the epithelial precursor
      cells for taste receptor cells start to exhibit neural properties during the
      differentiation of the taste receptor cells. The expression of the neural
      specific transcription factors Mash-1 and Prox-1 in the nervous system is
      transient and precedes neuronal differentiation. Therefore, we examined the
      expression of Mash-1 and Prox-1 in the epithelium of circumvallate papillae of
      the tongue in order to clarify the localization of the precursor cells with
      neural properties and observed that both expressions are restricted to the taste
      buds. Two-colour in situ hybridization showed that the signals for Mash-1 did not
      overlap those for taste receptor cell-specific genes such as gustducin and T1R2.
      In the process of development and regeneration of the taste buds, the expression
      of Mash-1 preceded that of gustducin and T1R2. These observations suggest that
      Mash-1 could be a candidate for a marker of immature taste receptor cells,
      including the cells that express gustducin and/or T1R2 at a later stage.

PMID- 12052782
TI  - A cluster of candidate odorant receptors from the malaria vector mosquito,
      Anopheles gambiae.
AB  - Olfaction is critical to the host preference selection behavior of many disease
      transmitting insects, including the mosquito Anopheles gambiae sensu stricto
      (hereafter A. gambiae), one of the major vectors for human malaria. In order to
      more fully understand the molecular biology of olfaction in this insect, we have
      previously identified several members member of a family of candidate odorant
      receptor proteins from A. gambiae (AgORs). Here we report the cloning and
      characterization of an additional AgOR gene, denoted as AgOr5, which shows
      significant similarity to putative odorant receptors in A. gambiae and Drosophila
      melanogaster and which is selectively expressed in olfactory organs. AgOr5 is
      tightly clustered within the A. gambiae genome to two other highly homologous
      candidate odorant receptors, suggesting that these genes are derived from a
      common ancestor. Analysis of the developmental expression within members of this
      AgOR gene cluster reveals considerable variation between these AgORs as compared
      to candidate odorant receptors from D. melanogaster.

PMID- 12052783
TI  - A high-throughput screening procedure for identifying mice with aberrant taste
      and oromotor function.
AB  - Little is known about how specific genes influence taste function in mammals. One
      of the most promising ways to fill this void is to screen the progeny of
      chemically mutagenized (or genetically altered) mice for aberrant taste
      phenotypes and then identify the mutated gene(s) that is associated with each
      taste anomaly. To exploit this approach, a high-throughput and robust screening
      procedure is needed. We have attempted to meet this demand by developing an
      automated procedure that assesses taste responsiveness of individual mice to
      palatable and unpalatable taste stimuli. We focused on three taste stimuli
      (quinine hydrochloride, QHCl; sodium chloride, NaCl; and sucrose) and one mouse
      strain (C57BL/6). We used a commercially available gustometer system that both
      monitors the licking responses of mice and controls the presentation of each
      taste stimulus during successive 5 s trials. We describe a screening procedure
      that (after 2 days of simple training) can generate a concentration-response
      curve for NaCl or sucrose during a single 30 min test session, and for QHCl over
      three 30 min test sessions. A normative database based on the responses of 98
      mice subjected to our screening procedure is also presented. We envision that
      investigators could use this normative database to assess taste function in the
      progeny of mutagenized (or genetically altered) mice. Any mouse that deviates
      significantly-e.g. three standard deviations (SD)-from the mean of the normative
      database would be flagged as having a potentially interesting mutation. We also
      developed an additional second screen for identifying mice with oromotor
      abnormalities. This latter screen is necessary because oromotor problems could
      lead to false positives or negatives in the screen for taste function, but is
      also useful for researchers interested in genes influencing oromotor circuitry.
      Throughout the development of the screening protocol, we sought to balance two
      conflicting demands: the need to maximize the screen's sensitivity and minimize
      its duration. This screen represents a significant improvement over the common
      two-bottle preference test because it assesses taste function more specifically
      and in a fraction of the time.

PMID- 12052784
TI  - Morphology and physiology of the serotonin-immunoreactive putative antennal lobe
      feedback neuron in the male silkmoth Bombyx mori.
AB  - In the male silkmoth Bombyx mori, olfactory information is relayed from olfactory
      receptor neurons in the antennae to the antennal lobe, and then to a variety of
      protocerebral neuropils. Currently, very little is known about neuromodulators
      that may affect the dynamics of this olfactory neural network. Immunocytochemical
      studies have revealed the presence of a serotonin-immunoreactive (SI) neuron
      that, in several insect species, is thought to provide feedback to the antennal
      lobe. To date, no studies have revealed details of this neuron's physiology.
      Using intracellular recording and staining, the silkmoth SI neuron (in two
      individuals) was first characterized physiologically and then stained with
      Lucifer Yellow to reveal morphological details. Immunocytochemical methods were
      also used to confirm the presence of serotonin. The silkmoth SI neuron branched
      in many important brain neuropils such as the mushroom body, central body,
      lateral accessory lobe and antennal lobe. The SI neuron in both individuals fired
      spontaneous, long duration action potentials, and responded to mechanosensory
      stimuli to the antennae.

PMID- 12052785
TI  - Managing antibiotic associated diarrhoea.

PMID- 12052786
TI  - The power of the press in smokers' attempts to quit.

PMID- 12052787
TI  - Intermediate care.

PMID- 12052788
TI  - Delaying folic acid fortification of flour.

PMID- 12052789
TI  - Physicians' and patients' choices in evidence based practice.

PMID- 12052793
TI  - Doctors condemn NICE's guidance on leukaemia drug.

PMID- 12052794
TI  - More women in the workforce reduces mortality.

PMID- 12052797
TI  - US and UK are top in teenage pregnancy rates.

PMID- 12052798
TI  - PFI critic rebuts criticism from select committee.

PMID- 12052799
TI  - Burden of illness and suicide in elderly people: case-control study.
AB  - OBJECTIVES: To study the association between physical illness and suicide in
      elderly people. DESIGN: Case-control with illness determined from interviews with
      relatives of people who committed suicide and with control participants and from
      medical records. SETTING: Gothenburg and two surrounding counties (210 703 people
      aged 65 years and over). PARTICIPANTS: Consecutive records of people who had
      committed suicide and had undergone forensic examination (46 men, 39 women) and
      living control participants from the tax register (84 men, 69 women). MAIN
      OUTCOME MEASURES: Physical illness rated in 13 organ systems according to the
      cumulative illness rating scale-geriatrics; serious physical illness (organ
      category score 3 or 4); overall score for burden of physical illness. RESULTS:
      Visual impairment (odds ratio 7.0, 95% confidence interval 2.3 to 21.4),
      neurological disorders (3.8, 1.5 to 9.4), and malignant disease (3.4, 1.2 to 9.8)
      were associated with increased risk for suicide. Serious physical illness in any
      organ category was an independent risk factor for suicide in the multivariate
      regression model (6.4, 2.0 to 20.0). When the sexes were analysed separately,
      serious physical illness was associated with suicide in men (4.2, 1.8 to 9.5) as
      was high burden of physical illness (2.8, 1.2 to 6.5). Such associations were not
      seen in women, possibly because of the small sample size. CONCLUSIONS: Visual
      impairment, neurological disorders, and malignant disease were independently
      associated with increased risk of suicide in elderly people. Serious physical
      illness may be a stronger risk factor for suicide in men than in women.

PMID- 12052800
TI  - Effect of routine zinc supplementation on pneumonia in children aged 6 months to
      3 years: randomised controlled trial in an urban slum.
AB  - OBJECTIVES: To evaluate the effect of daily zinc supplementation in children on
      the incidence of acute lower respiratory tract infections and pneumonia. DESIGN:
      Double masked, randomised placebo controlled trial. SETTING: A slum community in
      New Delhi, India. PARTICIPANTS: 2482 children aged 6 to 30 months. INTERVENTIONS:
      Daily elemental zinc, 10 mg to infants and 20 mg to older children or placebo for
      four months. Both groups received single massive dose of vitamin A (100 000 IU
      for infants and 200 000 IU for older children) at enrollment. MAIN OUTCOME
      MEASURES: All households were visited weekly. Any children with cough and lower
      chest indrawing or respiratory rate 5 breaths per minute less than the World
      Health Organization criteria for fast breathing were brought to study physicians.
      RESULTS: At four months the mean plasma zinc concentration was higher in the zinc
      group (19.8 (SD 10.1) v 9.3 (2.1) micromol/l, P<0.001). The proportion of
      children who had acute lower respiratory tract infection during follow up was no
      different in the two groups (absolute risk reduction -0.2%, 95% confidence
      interval -3.9% to 3.6%). Zinc supplementation resulted in a lower incidence of
      pneumonia than placebo (absolute risk reduction 2.5%, 95% confidence interval
      0.4% to 4.6%). After correction for multiple episodes in the same child by
      generalised estimating equations analysis the odds ratio was 0.74, 95% confidence
      interval 0.56 to 0.99. CONCLUSIONS: Zinc supplementation substantially reduced
      the incidence of pneumonia in children who had received vitamin A.

PMID- 12052802
TI  - Science commentary: Probiotics.

PMID- 12052801
TI  - Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis.
AB  - OBJECTIVE: To evaluate efficacy of probiotics in prevention and treatment of
      diarrhoea associated with the use of antibiotics. DESIGN: Meta-analysis; outcome
      data (proportion of patients not getting diarrhoea) were analysed, pooled, and
      compared to determine odds ratios in treated and control groups. IDENTIFICATION:
      Studies identified by searching Medline between 1966 and 2000 and the Cochrane
      Library. Studies reviewed Nine randomised, double blind, placebo controlled
      trials of probiotics. RESULTS: Two of the nine studies investigated the effects
      of probiotics in children. Four trials used a yeast (Saccharomyces boulardii),
      four used lactobacilli, and one used a strain of enterococcus that produced
      lactic acid. Three trials used a combination of probiotic strains of bacteria. In
      all nine trials, the probiotics were given in combination with antibiotics and
      the control groups received placebo and antibiotics. The odds ratio in favour of
      active treatment over placebo in preventing diarrhoea associated with antibiotics
      was 0.39 (95% confidence interval 0.25 to 0.62; P<0.001) for the yeast and 0.34
      (0.19 to 0.61; P<0.01 for lactobacilli. The combined odds ratio was 0.37 (0.26 to
      0.53; P<0.001) in favour of active treatment over placebo. CONCLUSIONS: The meta
      analysis suggests that probiotics can be used to prevent antibiotic associated
      diarrhoea and that S boulardii and lactobacilli have the potential to be used in
      this situation. The efficacy of probiotics in treating antibiotic associated
      diarrhoea remains to be proved. A further large trial in which probiotics are
      used as preventive agents should look at the costs of and need for routine use of
      these agents.

PMID- 12052803
TI  - Nottingham Staphylococcus aureus population study: prevalence of MRSA among
      elderly people in the community.

PMID- 12052804
TI  - Longitudinal study of genital infection by herpes simplex virus type 1 in Western
      Scotland over 15 years.

PMID- 12052805
TI  - Follow up after a family based genetic screening programme for familial
      hypercholesterolaemia: is screening alone enough?

PMID- 12052806
TI  - Research pointers: Association of common genetic variant with susceptibility to
      invasive pneumococcal disease.

PMID- 12052807
TI  - Detecting patients at a high risk of developing chronic obstructive pulmonary
      disease in general practice: cross sectional case finding study.
AB  - OBJECTIVES: To investigate the effectiveness of case finding of patients at risk
      of developing chronic obstructive pulmonary disease, whether the method is
      suitable for use in general practice, how patients should be selected, and the
      time required. DESIGN: Cross sectional study. SETTING: Two semirural general
      practices in the Netherlands. PARTICIPANTS: 651 smokers aged 35 to 70 years. MAIN
      OUTCOME MEASURES: Short standardised questionnaire on bronchial symptoms for
      current smokers, lung function with a spirometer, and the quality of the
      spirometric curve. RESULTS: Of the 201 smokers not taking drugs for a pulmonary
      condition, 169 produced an acceptable curve (fulfilling American Thoracic Society
      criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced
      expiratory volume in one second (FEV(1)) <80% of predicted. When smokers were
      preselected on the basis of chronic cough, the proportion with an FEV(1) <80% of
      predicted increased to 27% (17 of 64; 12% to 38%). Chronic cough was a better
      predictor of airflow obstruction than other symptoms, such as wheeze and
      dyspnoea. The presence of two symptoms was a slightly better predictor than cough
      only (odds ratio 3.02 (1.37 to 6.64) v 2.50 (1.14 to 5.52)). Age was also a good
      predictor of obstruction; smokers over 60 with cough had a 48% chance of having
      an obstruction. The mean time needed for spirometry was four minutes. Detecting
      one smoker with an FEV(1) <80% of predicted cost 5 pound sterling to 10 pound
      sterling. CONCLUSIONS: Trained practice assistants could check all patients who
      smoke for chronic obstructive pulmonary disease at little cost to the practice.
      Cough and age are the most important predictors of the disease. By testing one
      smoker a day, an average practice could identify one patient at risk a week.

PMID- 12052808
TI  - Burden of corticosteroids in children with asthma in primary care: retrospective
      observational study.

PMID- 12052809
TI  - 10-minute consultation. Newly diagnosed hypertension.

PMID- 12052810
TI  - Childhood atopic eczema.

PMID- 12052811
TI  - Lesson of the week: Osteomyelitis in the well looking afebrile child.

PMID- 12052812
TI  - ABC of clinical electrocardiography: Paediatric electrocardiography.

PMID- 12052813
TI  - Effect of a scoring system and protocol for sedation on duration of patients'
      need for ventilator support in a surgical intensive care unit.
AB  - PROBLEM: Need for improved sedation strategy for adults receiving ventilator
      support. DESIGN: Observational study of effect of introduction of guidelines to
      improve the doctors' and nurses' performance. The project was a prospective
      improvement and was part of a national quality improvement collaborative.
      BACKGROUND AND SETTING: A general mixed surgical intensive care unit in a
      university hospital; all doctors and nurses in the unit; all adult patients (>18
      years) treated by intermittent positive pressure ventilation for more than 24
      hours. KEY MEASURES FOR IMPROVEMENT: Reduction in patients' mean time on a
      ventilator and length of stay in intensive care over a period of 11 months;
      anonymous reporting of critical incidents; staff perceptions of ease and of
      consequences of changes. STRATEGIES FOR CHANGE: Multiple measures (protocol
      development, educational presentations, written guidelines, posters, flyers,
      emails, personal discussions, and continuous feedback) were tested, rapidly
      assessed, and adopted if beneficial. EFFECTS OF CHANGE: Mean ventilator time
      decreased by 2.1 days (95% confidence interval 0.7 to 3.6 days) from 7.4 days
      before intervention to 5.3 days after. Mean stay decreased by 1.0 day (-0.9 to
      2.9 days) from 9.3 days to 8.3 days. No accidental extubations or other incidents
      were identified. LESSONS LEARNT: Relatively simple changes in sedation practice
      had significant effects on length of ventilator support. The change process was
      well received by the staff and increased their interest in identifying other
      areas for improvement.

PMID- 12052814
TI  - Clinical endpoints in trials of drugs for cancer: time for a rethink?

PMID- 12052815
TI  - Storm over screening for prostate specific antigen. Right to choose is important.

PMID- 12052816
TI  - MMR uptake data are unlikely to be subject to manipulation.

PMID- 12052817
TI  - Fusidic acid cream for impetigo. Fusidic acid should be used with restraint.

PMID- 12052818
TI  - Eye drops and patches both in fact work for amblyopia.

PMID- 12052819
TI  - The power of shame. Behaviour should be distinguished from identity.

PMID- 12052820
TI  - Clinical quality should be put at the centre of care.

PMID- 12052821
TI  - Declining altruism in medicine. Good service is voluntary.

PMID- 12052822
TI  - Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter.
AB  - Members of the Wnt family of secreted molecules have been established as key
      factors in determining cell fate and morphogenic signaling. It has long been
      recognized that Wnt induces morphogenic signaling through the Tcf/LEF-1 cascade
      by regulating free intracellular levels of beta-catenin, a co-factor for Tcf/LEF
      1 transcription factors. In the present study, we have demonstrated that Wnt-3A
      can also directly induce transcription from the LEF-1 promoter. This induction
      was dependent on glycogen synthase kinase 3beta inactivation, a rise in free
      intracellular beta-catenin, and a short 110-bp Wnt-responsive element (WRE) in
      the LEF-1 promoter. Linear and internal deletion of this WRE led to a dramatic
      increase in constitutive LEF-1 promoter activity and loss of Wnt-3A
      responsiveness. In isolation, the 110-bp WRE conferred context-independent Wnt-3A
      or beta-catenin(S37A) responsiveness to a heterologous SV40 promoter. Studies
      expressing dominant active and negative forms of LEF-1, beta-catenin, GSK-3beta,
      and beta-catenin/LEF-1 fusions suggest that Wnt-3A activates the LEF-1 promoter
      through a beta-catenin-dependent and LEF-1-independent process. Wnt-3A expression
      also induced multiple changes in the binding of factors to the WRE and suggests
      that regulatory mechanisms may involve modulation of a multiprotein complex. In
      summary, these results provide evidence for transcriptional regulation of the LEF
      1 promoter by Wnt and enhance the mechanistic understanding of Wnt/beta-catenin
      signaling in the regulation of LEF-1-dependent developmental processes.

PMID- 12052823
TI  - Akt is a downstream target of NF-kappa B.
AB  - The ubiquitously expressed transcription factor NF-kappa B and the serine
      threonine kinase Akt both are involved in the promotion of cell survival.
      Although initially believed to operate as components of distinct signaling
      pathways, several studies have demonstrated that the NF-kappa B and Akt signaling
      pathways can converge. Indeed, I kappa B kinase, the kinase involved in NF-kappa
      B activation, is a substrate of Akt, and activation of Akt therefore stimulates
      NF-kappa B activity. Although these results place Akt upstream of NF-kappa B
      activation in the sequence of signaling events, we report that this may not
      necessarily be the case and that Akt is a downstream target of NF-kappa B.
      Treatment of NIH3T3 cells with the NF-kappa B activators, tumor necrosis factor
      (TNF) alpha and lipopolysaccharide, results in the stimulation of Akt
      phosphorylation. The stimulation of Akt is, however, detected only after I kappa
      B-alpha degradation is induced by these agents. The nuclear translocation of p65
      and increased DNA binding activity of NF-kappa B also precede Akt
      phosphorylation. Treatment with two pharmacological inhibitors of NF-kappa B,
      SN50 and N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), blocks TNF-induced
      Akt activation. On the other hand TNF-mediated NF-kappa B activation is not
      reduced by the phosphoinositide-3 kinase inhibitors wortmannin and LY294002,
      although these inhibitors completely block the activation of Akt. These results
      suggest that NF-kappa B is required for TNF-mediated Akt activation and that it
      lies upstream of the stimulation of Akt. Consistent with this conclusion is the
      finding that overexpression of p65/RelA leads to Akt phosphorylation in the
      absence of extracellular stimulatory factors, whereas overexpression of I kappa B
      alpha reduces Akt phosphorylation below basal levels. Interestingly, in addition
      to stimulating the phosphorylation of Akt, overexpression of p65 causes an
      increase in the expression of Akt mRNA and protein.

PMID- 12052824
TI  - Lithocholic acid decreases expression of bile salt export pump through farnesoid
      X receptor antagonist activity.
AB  - Bile salt export pump (BSEP) is a major bile acid transporter in the liver.
      Mutations in BSEP result in progressive intrahepatic cholestasis, a severe liver
      disease that impairs bile flow and causes irreversible liver damage. BSEP is a
      target for inhibition and down-regulation by drugs and abnormal bile salt
      metabolites, and such inhibition and down-regulation may result in bile acid
      retention and intrahepatic cholestasis. In this study, we quantitatively analyzed
      the regulation of BSEP expression by FXR ligands in primary human hepatocytes and
      HepG2 cells. We demonstrate that BSEP expression is dramatically regulated by
      ligands of the nuclear receptor farnesoid X receptor (FXR). Both the endogenous
      FXR agonist chenodeoxycholate (CDCA) and synthetic FXR ligand GW4064 effectively
      increased BSEP mRNA in both cell types. This up-regulation was readily detectable
      at as early as 3 h, and the ligand potency for BSEP regulation correlates with
      the intrinsic activity on FXR. These results suggest BSEP as a direct target of
      FXR and support the recent report that the BSEP promoter is transactivated by
      FXR. In contrast to CDCA and GW4064, lithocholate (LCA), a hydrophobic bile acid
      and a potent inducer of cholestasis, strongly decreased BSEP expression. Previous
      studies did not identify LCA as an FXR antagonist ligand in cells, but we show
      here that LCA is an FXR antagonist with partial agonist activity in cells. In an
      in vitro co-activator association assay, LCA decreased CDCA- and GW4064-induced
      FXR activation with an IC(50) of 1 microm. In HepG2 cells, LCA also effectively
      antagonized GW4064-enhanced FXR transactivation. These data suggest that the
      toxic and cholestatic effect of LCA in animals may result from its down
      regulation of BSEP through FXR. Taken together, these observations indicate that
      FXR plays an important role in BSEP gene expression and that FXR ligands may be
      potential therapeutic drugs for intrahepatic cholestasis.

PMID- 12052825
TI  - MAP kinase cascades are activated in astrocytes and preadipocytes by 15-deoxy
      Delta(12-14)-prostaglandin J(2) and the thiazolidinedione ciglitazone through
      peroxisome proliferator activator receptor gamma-independent mechanisms involving
      reactive oxygenated species.
AB  - 15-Deoxy-Delta(12-14)-prostaglandin J(2) (dPGJ2) and thiazolidinediones are known
      as ligands for the peroxisome proliferator activator receptor gamma (PPAR gamma)
      a member of the nuclear receptor superfamily. Herein, we show that dPGJ2
      activates, in cultured primary astrocytes, Erk, Jnk, p38 MAP kinase, and ASK1, a
      MAP kinase kinase kinase, which can be involved in the activation of Jnk and p38
      MAP kinase. The activation kinetic is similar for the three MAP kinase. The
      activation of the MAP kinases is detectable around 0.5 h. The activation
      increases with dPGJ2 in a dose dependent manner (0-15 microm). A scavenger of
      reactive oxygenated species (ROS), N-acetylcysteine (NAC) at 20 mm, completely
      suppresses the activation of MAP kinases and ASK1, suggesting a role for
      oxidative stress in the activation mechanism. Other prostaglandin cyclopentenones
      than dPGJ2, A(2), and to a lesser degree, A(1) also stimulate the MAP kinases,
      although they do not bind to PPAR gamma. Ciglitazone (20 microm), a
      thiazolidinedione that mimics several effects of dPGJ2 in different cell types,
      also activates the three MAP kinase families and ASK1 in cultured astrocytes.
      However the activation is more rapid (it is detectable at 0.25 h) and more
      sustained (it is still strong after 4 h). NAC prevents the activation of the
      three MAP kinase families by ciglitazone. Another thiazolidinedione that binds to
      PPAR gamma, rosiglitazone, does not activate MAP kinases, indicating that the
      effect of ciglitazone on MAP kinases is independent of PPAR gamma. Ciglitazone
      and less strongly dPGJ2 activate Erk in undifferentiated cells of the adipocyte
      cell line 1B8. Ciglitazone also activates Jnk and p38 MAP kinase in these
      preadipocytes. Our findings suggest that a part of the biological effects of
      dPGJ2 and ciglitazone involve the activation of the three MAP kinase families
      probably through PPAR gamma-independent mechanisms involving ROS.

PMID- 12052826
TI  - Localization of the lectin, ERp57 binding, and polypeptide binding sites of
      calnexin and calreticulin.
AB  - Calnexin and calreticulin are membrane-bound and soluble chaperones,
      respectively, of the endoplasmic reticulum (ER) which interact transiently with a
      broad spectrum of newly synthesized glycoproteins. In addition to sharing
      substantial sequence identity, both calnexin and calreticulin bind to
      monoglucosylated oligosaccharides of the form Glc(1)Man(5-9)GlcNAc(2), interact
      with the thiol oxidoreductase, ERp57, and are capable of acting as chaperones in
      vitro to suppress the aggregation of non-native proteins. To understand how these
      diverse functions are coordinated, we have localized the lectin, ERp57 binding,
      and polypeptide binding sites of calnexin and calreticulin. Recent structural
      studies suggest that both proteins consist of a globular domain and an extended
      arm domain comprised of two sequence motifs repeated in tandem. Our results
      indicate that the primary lectin site of calnexin and calreticulin resides within
      the globular domain, but the results also point to a much weaker secondary site
      within the arm domain which lacks specificity for monoglucosylated
      oligosaccharides. For both proteins, a site of interaction with ERp57 is centered
      on the arm domain, which retains approximately 50% of binding compared with full
      length controls. This site is in addition to a Zn(2+)-dependent site located
      within the globular domain of both proteins. Finally, calnexin and calreticulin
      suppress the aggregation of unfolded proteins via a polypeptide binding site
      located within their globular domains but require the arm domain for full
      chaperone function. These findings are integrated into a model that describes the
      interaction of glycoprotein folding intermediates with calnexin and calreticulin.

PMID- 12052827
TI  - The N-terminal coiled coil domain of the cytohesin/ARNO family of guanine
      nucleotide exchange factors interacts with the scaffolding protein CASP.
AB  - Cytohesin is a guanine nucleotide exchange factor that regulates members of the
      ADP-ribosylation factor (ARF) family of small GTPases. All of the members of the
      cytohesin family (including ARNO, ARNO3, and the newly characterized cytohesin-4)
      have a similar domain distribution consisting of a Sec7 homology domain, a
      pleckstrin homology domain, and an N-terminal coiled coil. In this study, we
      attempt to identify proteins that interact specifically with the coiled coil
      motif of cytohesin. Yeast two-hybrid screening of a B cell library using the
      cytohesin N terminus as bait, identified CASP, a scaffolding protein of
      previously unknown function, as a binding partner. CASP contains an internal
      coiled coil motif that is required for cytohesin binding both in vitro and in COS
      1 cells. The specificity of the coiled coil of CASP is not restricted to
      cytohesin, however, because it is also capable of interacting with other members
      of the cytohesin/ARNO family, ARNO and ARNO3. In immunofluorescence experiments,
      CASP localizes to perinuclear tubulovesicular structures that are in close
      proximity to the Golgi. These structures remain relatively undisturbed when the
      cells are treated with brefeldin A. In epidermal growth factor-stimulated COS-1
      cells overexpressing cytohesin and CASP, cytohesin recruits CASP to membrane
      ruffles, revealing a functional interaction between the two proteins. These
      observations collectively suggest that CASP is a scaffolding protein that
      facilitates the function of at least one member of the cytohesin/ARNO family in
      response to specific cellular stimuli.

PMID- 12052828
TI  - Expression of recombinant Plasmodium falciparum subtilisin-like protease-1 in
      insect cells. Characterization, comparison with the parasite protease, and
      homology modeling.
AB  - Serine proteases play crucial roles in erythrocyte invasion by merozoites of the
      malaria parasite. Plasmodium falciparum subtilisin-like protease-1 (PfSUB-1) is
      synthesized during maturation of the intraerythrocytic parasite and accumulates
      in a set of merozoite secretory organelles, suggesting that it may play a role in
      host cell invasion or post-invasion events. We describe the production,
      purification, and characterization of recombinant PfSUB-1 and comparison with the
      authentic protease detectable in parasite extracts. The recombinant protease
      requires high levels of calcium for optimum activity and has an alkaline pH
      optimum. Using a series of decapeptide and protein substrates, PfSUB-1 was found
      to have a relaxed substrate specificity with regard to the P1 position but is
      unable to efficiently cleave substrates with a P1 leucine residue. Similarly,
      replacement of a P4 valine with alanine severely reduced cleavage efficiency,
      whereas its replacement with lysine abolished cleavage. In all respects
      investigated, the recombinant protease was indistinguishable from parasite
      derived enzyme. Three-dimensional homology modeling of the PfSUB-1 catalytic
      domain based on an alignment with closely related bacterial subtilisins and an
      orthologue from the rodent malaria Plasmodium yoelii suggests that the protease
      has at least three potential calcium ion-binding sites, three intramolecular
      disulfide bridges, and a single free cysteine within the enzyme S1 pocket. A
      predicted highly polar S1 pocket and a hydrophobic S4 subsite are in broad
      agreement with the experimentally determined substrate specificity.

PMID- 12052829
TI  - Serine/threonine phosphorylation of ShcA. Regulation of protein-tyrosine
      phosphatase-pest binding and involvement in insulin signaling.
AB  - Serine phosphorylation of the ShcA signaling molecule has been reported recently.
      In this work, we have identified 12-O-tetradecanoylphorbol-13-acetate (TPA)- and
      growth factor-induced serine/threonine phosphorylation sites in p52(Shc) and
      p66(Shc). Among them, Ser(29) in p52(Shc) (equivalent to Ser(138) in p66(Shc))
      was phosphorylated only after TPA stimulation. Phosphorylation of this site
      together with the intact phosphotyrosine-binding domain was essential for ShcA
      binding to the protein-tyrosine phosphatase PTP-PEST. TPA-induced ShcA
      phosphorylation at this site (and hence, its association with PTP-PEST) was
      inhibited by a protein kinase C-specific inhibitor and was induced by
      overexpression of constitutively active mutants of protein kinase Calpha, 
      epsilon, and -delta isoforms. Insulin also induced ShcA/PTP-PEST association,
      although to a lesser extent than TPA. Overexpression of a PTP-PEST binding
      defective mutant of p52(Shc) (S29A) enhanced insulin-induced ERK activation in
      insulin receptor-overexpressing HIRc-B cells. Consistent with this, p52(Shc) S29A
      was more tyrosine-phosphorylated than wild-type p52(Shc) after insulin
      stimulation. Thus, we have identified a new mechanism whereby serine
      phosphorylation of ShcA controls the ability of its phosphotyrosine-binding
      domain to bind PTP-PEST, which is responsible for the dephosphorylation and down
      regulation of ShcA after insulin stimulation.

PMID- 12052830
TI  - The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide
      activation of signaling pathways and expression of inflammatory mediators in
      human monocytic cells.
AB  - Monocytes and macrophages express cytokines and procoagulant molecules in various
      inflammatory diseases. In sepsis, lipopolysaccharide (LPS) from Gram-negative
      bacteria induces tumor necrosis factor-alpha (TNF-alpha) and tissue factor (TF)
      in monocytic cells via the activation of the transcription factors Egr-1, AP-1,
      and nuclear factor-kappa B. However, the signaling pathways that negatively
      regulate LPS-induced TNF-alpha and TF expression in monocytic cells are currently
      unknown. We report that inhibition of the phosphatidylinositol 3-kinase (PI3K)
      Akt pathway enhances LPS-induced activation of the mitogen-activated protein
      kinase pathways (ERK1/2, p38, and JNK) and the downstream targets AP-1 and Egr-1.
      In addition, inhibition of PI3K-Akt enhanced LPS-induced nuclear translocation of
      nuclear factor-kappa B and prevented Akt-dependent inactivation of glycogen
      synthase kinase-beta, which increased the transactivational activity of p65. We
      propose that the activation of the PI3K-Akt pathway in human monocytes limits the
      LPS induction of TNF-alpha and TF expression. Our study provides new insight into
      the inhibitory mechanism by which the PI3K-Akt pathway ensures transient
      expression of these potent inflammatory mediators.

PMID- 12052831
TI  - Phosphorylation of VP30 impairs ebola virus transcription.
AB  - Transcription of the highly pathogenic Ebola virus (EBOV) is dependent on VP30, a
      constituent of the viral nucleocapsid complex. Here we present evidence that
      phosphorylation of VP30, which takes place at six N-terminal serine residues and
      one threonine residue, is of functional significance. Replacement of the
      phosphoserines by alanines resulted in an only slightly phosphorylated VP30
      (VP30(6A)) that is still able to activate EBOV-specific transcription in a
      plasmid-based minigenome system. VP30(6A), however, did not bind to inclusions
      that are induced by the major nucleocapsid protein NP. Three intracellular
      phosphatases (PP1, PP2A, and PP2C) have been determined to dephosphorylate VP30.
      The presence of okadaic acid (OA), an inhibitor of PP1 and PP2A, had the same
      negative effect on transcription activation by VP30 as the substitution of the
      six phosphoserines for aspartate residues. OA, however, did not impair
      transcription when VP30 was replaced by VP30(6A). In EBOV-infected cells, OA
      blocked virus growth dose-dependently. The block was mediated by the extensive
      phosphorylation of VP30, which is evidenced by the result that expression of
      VP30(6A), in trans, led to the progression of EBOV infection in the presence of
      OA. In conclusion, phosphorylation of VP30 was shown to regulate negatively
      transcription activation and positively binding to the NP inclusions.

PMID- 12052833
TI  - Isolation, characterization, and cDNA sequence of a carotenoid binding protein
      from the silk gland of Bombyx mori larvae.
AB  - A carotenoid binding protein (CBP) has been isolated from the silk glands of
      Bombyx mori larvae. The protein has an apparent molecular mass of 33 kDa and
      binds carotenoids in a 1:1 molar ratio. Lutein accounts for 90% of the bound
      carotenoids, whereas alpha-carotene and beta-carotene are minor components.
      Immunological analysis demonstrated the presence of CBP only in the yellow
      colored tissues of the silk gland, midgut, testis, and ovary. Several phenotypes
      of B. mori mutants linked to carotenoid transport have been utilized to
      characterize CBP. The Y (yellow hemolymph) gene controls uptake of carotenoids
      from the midgut lumen into the midgut epithelium, and larvae with the +(Y) gene
      lack this property. Immunoblotting analysis confirmed the presence of CBP in
      mutants with the dominant Y gene only. Immunohistochemistry verified the
      localization of CBP in the villi of the midgut epithelium, indicating that CBP
      might be involved in absorption of carotenoids. A cDNA clone for CBP encoding a
      protein of 297 amino acids has been isolated from the B. mori silk gland cDNA
      library. The deduced amino acid sequence revealed that CBP is a novel member of
      the steroidogenic acute regulatory (StAR) protein family with its unique
      structural feature of a StAR-related lipid transfer domain, known to aid in lipid
      transfer and recognition. Lutein-binding capacity of the recombinant CBP (rCBP)
      determined by incubating rCBP with lutein followed by immunoprecipitation using
      anti-CBP IgG conjugated to protein A-Sepharose, demonstrated the formation of a
      lutein-rCBP complex. Sequence analyses coupled with binding specificity suggest
      that CBP is a new member of the StAR protein family that binds carotenoids rather
      than cholesterol.

PMID- 12052832
TI  - Small inhibitory RNA duplexes for Sp1 mRNA block basal and estrogen-induced gene
      expression and cell cycle progression in MCF-7 breast cancer cells.
AB  - Small interfering RNA duplexes containing 21-22 nucleotides that mediate sequence
      specific mRNA degradation and inhibitory RNA (iRNA) for Sp1 mRNA were used in
      this study to investigate the role of Sp1 on basal and hormone-induced growth and
      transactivation in MCF-7 and ZR-75 human breast cancer cells. Transfection of Sp1
      iRNA in MCF-7 or ZR-75 cells for 36-44 h decreased Sp1 protein (50-70%) in
      nuclear extracts, and immunohistochemical analysis showed that the Sp1 protein in
      transfected MCF-7 cells was barely detectable. In cell cycle progression studies
      in MCF-7 cells, decreased Sp1 protein was accompanied by a decrease in cells in
      the S phase and an increase in cells in G(0)/G(1), and estrogen-induced G(0)/G(1)
      --> S phase progression was inhibited in cells treated with iRNA for Sp1. Sp1
      iRNA also specifically blocked basal and estrogen-induced transactivation in
      cells transfected with a GC-rich construct linked to a luciferase reporter gene
      (pSp1(3)), and this was accompanied by decreased Sp1 binding to this GC-rich
      promoter as determined in gel mobility shift and chromatin immunoprecipitation
      assays. These results clearly demonstrate the key role of the Sp1 protein in
      basal and estrogen-induced growth and gene expression in breast cancer cells.

PMID- 12052834
TI  - Regulation of two JunD isoforms by Jun N-terminal kinases.
AB  - The JunD transcription factor is one member of the Jun family of proteins that
      also includes c-Jun and JunB. Although c-Jun can function to promote cell
      proliferation and can cooperate with other oncogenes to transform cells, JunD
      slows proliferation of fibroblasts and antagonizes transformation by activated
      ras. Two isoforms of JunD, a full-length isoform containing 341 amino acids (JunD
      FL) and a truncated isoform lacking 48 amino acids at the N terminus (Delta
      JunD), are generated through utilization of two translation start sites within a
      single mRNA. Here we show that both isoforms of JunD are phosphorylated by Jun N
      terminal kinases (JNKs) at three identical residues and that both contain a
      docking domain that specifically binds JNKs. The JunD-FL isoform binds to and is
      phosphorylated by JNK more efficiently than Delta JunD in vitro; correspondingly,
      JunD-FL is a more potent transcriptional activator than Delta JunD. Although
      increased JNK signaling can activate both JunD isoforms, mutating either the JNK
      docking domain or the target JNK phosphorylation sites blocks this activation.
      These results identify two distinct isoforms of JunD with differential responses
      to JNK signaling pathways.

PMID- 12052835
TI  - Hsp90 regulates a von Hippel Lindau-independent hypoxia-inducible factor-1 alpha
      degradative pathway.
AB  - HIF-1 alpha is a normally labile proangiogenic transcription factor that is
      stabilized and activated in hypoxia. Although the von Hippel Lindau (VHL) gene
      product, the ubiquitin ligase responsible for regulating HIF-1 alpha protein
      levels, efficiently targets HIF-1 alpha for rapid proteasome-dependent
      degradation under normoxia, HIF-1 alpha is resistant to the destabilizing effects
      of VHL under hypoxia. HIF-1 alpha also associates with the molecular chaperone
      Hsp90. To examine the role of Hsp90 in HIF-1 alpha function, we used renal
      carcinoma cell (RCC) lines that lack functional VHL and express stable HIF-1
      alpha protein under normoxia. Geldanamycin (GA), an Hsp90 antagonist, promoted
      efficient ubiquitination and proteasome-mediated degradation of HIF-1 alpha in
      RCC in both normoxia and hypoxia. Furthermore, HIF-1 alpha point mutations that
      block VHL association did not protect HIF-1 alpha from GA-induced
      destabilization. Hsp90 antagonists also inhibited HIF-1 alpha transcriptional
      activity and dramatically reduced both hypoxia-induced accumulation of VEGF mRNA
      and hypoxia-dependent angiogenic activity. These findings demonstrate that
      disruption of Hsp90 function 1) promotes HIF-1 alpha degradation via a novel,
      oxygen-independent E3 ubiquitin ligase and 2) diminishes HIF-1 alpha
      transcriptional activity. Existence of an Hsp90-dependent pathway for elimination
      of HIF-1 alpha predicts that Hsp90 antagonists may be hypoxic cell sensitizers
      and possess antiangiogenic activity in vivo, thus extending the utility of these
      drugs as therapeutic anticancer agents.

PMID- 12052836
TI  - Fatty acid transport in Saccharomyces cerevisiae. Directed mutagenesis of FAT1
      distinguishes the biochemical activities associated with Fat1p.
AB  - The fatty acid transport protein Fat1p functions as a component of the long-chain
      fatty acid transport apparatus in the yeast Saccharomyces cerevisiae. Fat1p has
      significant homologies to the mammalian fatty acid transport proteins (FATP) and
      the very long-chain acyl-CoA synthetases (VLACS). In order to further understand
      the functional roles intrinsic to Fat1p (fatty acid transport and VLACS
      activities), a series of 16 alleles carrying site-directed mutations within FAT1
      were constructed and analyzed. Sites chosen for the construction of amino acid
      substitutions were based on conservation between Fat1p and the mammalian FATP
      orthologues and included the ATP/AMP and FATP/VLACS signature motifs. Centromeric
      and 2 mu plasmids encoding mutant forms of Fat1p were transformed into a yeast
      strain containing a deletion in FAT1 (fat1Delta). For selected subsets of FAT1
      mutant alleles, we observed differences between the wild type and mutants in 1)
      growth rates when fatty acid synthase was inhibited with 45 microm cerulenin in
      the presence of 100 microm oleate (C(18:1)), 2) levels of fatty acid import
      monitored using the accumulation of the fluorescent fatty acid 4,4-difluoro-5
      methyl-4-bora-3a,4a-diaza-S-indacene-3-dodecanoic acid and [(3)H]oleate, 3)
      levels of lignoceryl (C(24:0)) CoA synthetase activities, and 4) fatty acid
      profiles monitored using gas chromatography/mass spectrometry. In most cases,
      there was a correlation between growth on fatty acid/cerulenin plates, the levels
      of fatty acid accumulation, very long-chain fatty acyl-CoA synthetase activities,
      and the fatty acid profiles in the different FAT1 mutants. For several notable
      exceptions, the fatty acid transport and very long-chain fatty acyl-CoA
      synthetase activities were distinguishable. The characterization of these novel
      mutants provides a platform to more completely understand the role of Fat1p in
      the linkage between fatty acid import and activation to CoA thioesters.

PMID- 12052837
TI  - Structural requirements for the recruitment of Gaa1 into a functional
      glycosylphosphatidylinositol transamidase complex.
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins are synthesized on membrane
      bound ribosomes, translocated across the endoplasmic reticulum membrane, and GPI
      anchored by GPI transamidase (GPIT). GPIT is a minimally heterotetrameric
      membrane protein complex composed of Gaa1, Gpi8, PIG-S and PIG-T. We describe
      structure-function analyses of Gaa1, the most hydrophobic of the GPIT subunits,
      with the aim of assigning a functional role to the different sequence domains of
      the protein. We generated epitope-tagged Gaa1 mutants and analyzed their membrane
      topology, subcellular distribution, complex-forming capability, and ability to
      restore GPIT activity in Gaa1-deficient cells. We show that (i) detergent
      extracted, Gaa1-containing GPIT complexes sediment unexpectedly rapidly at
      approximately 17 S, (ii) Gaa1 is an endoplasmic reticulum-localized membrane
      glycoprotein with a cytoplasmically oriented N terminus and a lumenally oriented
      C terminus, (iii) elimination of C-terminal transmembrane segments allows Gaa1 to
      interact with other GPIT subunits but renders the resulting GPIT complex
      nonfunctional, (iv) interaction between Gaa1 and other GPIT subunits occurs via
      the large lumenal domain of Gaa1 located between the first and second
      transmembrane segments, and (v) the cytoplasmic N terminus of Gaa1 is not
      required for formation of a functional GPIT complex but may act as a membrane
      sorting determinant directing Gaa1 and associated GPIT subunits to an endoplasmic
      reticulum membrane domain.

PMID- 12052838
TI  - Genomewide linkage scan of resting blood pressure: HERITAGE Family Study. Health,
      Risk Factors, Exercise Training, and Genetics.
AB  - The purpose of this study was to search for genomic regions influencing resting
      systolic (SBP) and diastolic (DBP) blood pressure (BP) in sedentary families
      (baseline), and for resting BP responses (changes) resulting from a 20-week
      exercise training intervention (post-training-baseline) in the Health, Risk
      Factors, Exercise Training, and Genetics (HERITAGE) Family Study. A genome-wide
      scan was conducted on 317 black individuals from 114 families and 519 white
      individuals from 99 families using a multipoint variance-components linkage model
      and a panel of 509 markers. Promising results were primarily, but not
      exclusively, found in the black families. Linkage evidence (P<0.0023) with
      baseline BP replicated other studies within a 1-logarithm of odds (LOD) interval
      on 2p14, 3p26.3, and 12q21.33, and provided new evidence on 3q28, 11q21, and
      19p12. Results for several known hypertension genes were less compelling. For
      response BP, results were not very strong, although markers on 13q11 were mildly
      suggestive (P<0.01). In conclusion, these HERITAGE data, in conjunction with
      results from previous genomewide scans, provide a basis for planning future
      investigations. The major areas warranting further study involve fine mapping to
      narrow down 3 regions on 2q, 3p, and 12q that may contain "novel" hypertension
      genes, additional typing of some biological candidate genes to determine whether
      they are the sources of these and other signals, multilocus investigations to
      understand how and to what extent some of these candidates may interact, and
      multivariate studies to characterize any pleiotropy.

PMID- 12052839
TI  - Linkage of essential hypertension to chromosome 18q.
AB  - We performed a genomewide scan with 904 microsatellite markers using 120 extended
      Icelandic families with 490 hypertensive patients. The families were identified
      by cross-matching a list of hypertensive patients from the Hypertension Clinic of
      the University Hospital (Landspitalinn) in Iceland with a genealogy database of
      the entire Icelandic nation. After adding 5 markers, we found linkage to
      chromosome 18q with an allele-sharing LOD score of 4.60 (P=2.1x 10(-6)). These
      results provide evidence for a novel susceptibility gene for essential
      hypertension on chromosome 18q and show that it is possible to study the genetics
      of essential hypertension without stratifying by subphenotypes.

PMID- 12052840
TI  - Conserved synteny in rat and mouse for a blood pressure QTL on human chromosome
      17.
AB  - Evidence for blood pressure quantitative trait loci (QTLs) on rat chromosome 10
      has been found in multiple independent studies. Analysis of the homologous region
      on human chromosome 17 revealed significant linkage to blood pressure. The
      critical segment on human chromosome 17 spans a large interval containing the
      genes Itga2b, Gfap, and Itgb3. Therefore, findings in the rat may help to refine
      the position of blood pressure-regulating loci, assuming a common molecular cause
      across species. However, it has recently been suggested that the gene order in
      human, rat, and mouse is not conserved in this region, leaving uncertainty about
      the overlap of the blood pressure- regulating region between human chromosome 17
      and rat chromosome 10. We have performed a detailed comparative analysis among
      human, mouse, and rat, defining the segment in question, by obtaining gene
      structure information in silico and by radiation hybrid mapping. It is of
      interest that this region also contains Wnk4, a gene previously identified to
      cause pseudohypoaldosteronism type II and human hypertension. Our results
      definitively show that the conserved synteny extends among human chromosome 17,
      rat chromosome 10, and mouse chromosome 11, demonstrating an overlap between
      previously localized blood pressure QTLs in humans and rats.

PMID- 12052841
TI  - ADD1 460W allele associated with cardiovascular disease in hypertensive
      individuals.
AB  - High blood pressure is a predictor of cardiovascular disease. Hence, genes
      contributing to essential hypertension may play a role in the etiology of
      cardiovascular disease. For this reason, we examined the association between the
      alpha-adducin (ADD1) G460W and G-protein beta3 subunit (GNB3) 825C>T
      polymorphisms and the prevalence of peripheral arterial disease (PAD) and
      incidence of coronary heart disease (CHD) in non-Hispanic whites from the
      Atherosclerosis Risk in Communities (ARIC) Study. PAD prevalence was defined by
      an ankle-brachial index, ie, the ratio of ankle systolic blood pressure to
      brachial artery systolic blood pressure, of </=0.90 for men and </=0.85 for
      women. CHD incidence was determined by following the ARIC cohort for a median of
      5.3 years for potential coronary events. Stratified random samples of the ARIC
      cohort (n=703 and n=684) were used, respectively, as the comparison groups for
      the PAD (n=144) and incident CHD (n=408) cases. The GNB3 825T allele and the ADD1
      460W allele were not significantly associated with prevalence of PAD or incidence
      of CHD. However, a test of the interaction between hypertension status and the
      ADD1 G460W polymorphism indicated that further evaluation of the ADD1
      polymorphism in only hypertensive individuals was warranted. The ADD1 460W allele
      was significantly associated with PAD (odds ratio [OR]: 2.61, 95% CI, 1.27-5.37,
      P=0.01) and CHD (hazard rate ratio [HRR]: 2.30, 95% CI, 1.20-4.42, P=0.01) in
      hypertensive individuals after adjustment for multiple cardiovascular disease
      risk factors. An interaction with hypertension in the association between the
      ADD1 G460W polymorphism and cardiovascular disease merits further testing in
      additional populations.

PMID- 12052842
TI  - Myocyte redistribution of GRK2 and GRK5 in hypertensive, heart-failure-prone
      rats.
AB  - Gprotein-coupled receptor kinases (GRKs) are known to be involved in the
      development of cardiac hypertrophy. Their exact role and subcellular distribution
      during cardiac hypertrophy and failure remain to be elucidated. We examined
      expression and subcellular distribution of GRK2 and GRK5 in the left ventricle of
      female spontaneously hypertensive heart failure (SHHF) rats at 6 months of age
      using Western blots and fluorescent confocal microscopy. GRK2 was expressed
      mainly in the Triton X-100 soluble fraction in the left ventricle with similar
      expression levels between SHHF and age-matched Wistar-Kyoto (WKY) rats. GRK2 had
      a striated pattern which colocalized with sarcomeric alpha-actinin and G protein
      in both SHHF and WKY rat myocytes and specifically accumulated in the
      intercalated disks of myocytes from SHHF but not WKY rats. GRK5 was expressed in
      both the Triton X-100 soluble fraction and Triton X-100 insoluble fraction in the
      left ventricle with similar expression levels between SHHF and WKY rats. GRK5
      distributed diffusely in the cytoplasm in both SHHF and WKY rat myocytes and
      specifically accumulated in the nucleus of myocytes from SHHF but not WKY rats.
      GRK5 colocalized with coilin, the major component of the nuclear substructure
      involved in RNA synthesis and processing. The results suggest different roles for
      GRK2 and GRK5 in G-protein signaling and RNA biogenesis. Subcellular
      redistribution of GRK2 and GRK5 may be involved in cardiac hypertrophy resulting
      from chronic hypertension.

PMID- 12052843
TI  - Urinary protein and essential hypertension in black and in white people.
AB  - The objectives of this work were to examine the association between urinary
      protein and blood pressure and to compare the pattern of urinary protein
      excretion with essential hypertension in people of European origin (whites) and
      in people of African or African-Caribbean origin (blacks) living in southwest
      London, United Kingdom. In the groups as a whole, there were no significant
      differences in total urinary protein excretion between blacks and whites
      (geometric means [95% CI]: 94.0 [85.9 to 102.9] mg/24h for the blacks [n=151] and
      102.1 [96.1 to 108.4] mg/24h for the whites [n= 219]). There were also no
      significant differences between blacks and whites in urinary albumin (6.5 [4.9 to
      8.5] mg/24h for the blacks [n=97] and 7.1 [5.6 to 9.0] mg/24h for the whites
      [n=123]). In both groups, those with essential hypertension displayed a
      significantly raised urinary protein excretion (1.21-fold higher for the blacks
      and 1.19-fold higher for the whites) and albumin excretion (1.69-fold higher for
      the blacks and 2.40-fold higher for the whites). Urinary transferrin excretion
      measured in a subgroup of 67 subjects was also raised in those with essential
      hypertension (3.22-fold higher in the blacks and 2.76-fold higher in the whites).
      Examination of urinary proteins by SDS-PAGE did not identify any pattern
      consistent with a reduction in renal tubular protein reabsorption in those with
      essential hypertension. These results suggest that the increase in protein
      excretion in essential hypertension could be due, at least in part, to an
      increase in glomerular protein ultrafiltration.

PMID- 12052844
TI  - Fetal uninephrectomy leads to postnatal hypertension and compromised renal
      function.
AB  - It has been proposed that the number of nephrons an individual has may be
      inversely related to his or her blood pressure. In this study using female ovine
      fetuses, nephron number was reduced by performing a fetal uninephrectomy during
      the period of active nephrogenesis (100 days of gestation, term=150 days). Lambs
      were born at term and grew at a similar rate. At 5 months of age, ovaries were
      removed and the carotid artery exteriorized into a fold of skin. Blood pressure
      and renal function were studied at 6 and 12 months of age. At 6 months of age,
      uninephrectomized lambs had significantly higher mean arterial blood pressure
      than sham-operated lambs (89+/-2 versus 82+/-2 mm Hg, P<0.05) when measured over
      a 3-day period. Heart rate was not different between the groups. Urine flow rate
      was similar, but glomerular filtration rate was significantly lower in
      uninephrectomized animals (P<0.05). Urinary concentrations and excretion rates of
      sodium tended to be higher in uninephrectomized animals but were similar for
      chloride and potassium. There was no evidence of proteinuria in the
      uninephrectomized lambs. Similar differences were observed in blood pressure and
      renal function at 12 months of age. Plasma renin concentrations at this age were
      lower in the uninephrectomized lambs (P<0.05). An oral salt load for 10 days did
      not increase blood pressure significantly in either group at 12 months of age,
      nor were there differences in the responsiveness to graded doses of angiotensin
      II. These results suggest that formation of a low nephron number in utero, may
      result in elevated blood pressure and compromised renal function in later life.

PMID- 12052845
TI  - Renoprotective effect of chronic adrenomedullin infusion in Dahl salt-sensitive
      rats.
AB  - The present study was designed to examine whether chronic adrenomedullin infusion
      has renoprotective effects in hypertensive renal failure and the mechanism by
      which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive
      rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks
      of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11
      week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control.
      After 7 weeks, untreated Dahl salt-sensitive rats were characterized by decreased
      kidney function, abnormal morphological findings, increased hormone levels,
      increased renal tissue angiotensin II levels, and altered mRNA expressions of
      transforming growth factor beta (TGF-beta) and components of the renin
      angiotensin system compared with Dahl salt-resistant rats. Chronic adrenomedullin
      treatment significantly improved renal function (serum creatinine -87%,
      creatinine clearance +114%, urinary protein excretion -59%) and histological
      findings (glomerular injury score -54%) without changing mean arterial pressure
      compared with untreated Dahl salt-sensitive rats. Interestingly, long-term human
      adrenomedullin infusion decreased the endogenous rat adrenomedullin level (-97%)
      with a slight increase of human adrenomedullin level. Chronic adrenomedullin
      treatment also significantly inhibited the increase of plasma renin concentration
      (-269%), aldosterone level (-82%), and renal tissue angiotensin II levels (-60%).
      Furthermore, adrenomedullin infusion significantly decreased the increases of
      mRNA expressions of TGF-beta (- 63%), angiotensin-converting enzyme (-137%),
      renin (-230%), and angiotensinogen (-38%) in renal cortex. These results suggest
      that increased endogenous adrenomedullin plays a compensatory role in chronic
      hypertensive renal failure and that long-term adrenomedullin infusion has
      renoprotective effects in this type of hypertension model, partly via inhibition
      of the circulating and renal renin-angiotensin system.

PMID- 12052846
TI  - Heart rate: an important confounder of pulse wave velocity assessment.
AB  - Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave
      velocity (PWV) is an index of arterial stiffness, and its prognostic value has
      been repeatedly emphasized. The purpose of the present study was to assess the
      effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8+/
      8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV
      was measured at 5 different pacing frequencies in the same session (60, 70, 80,
      90, 100 bpm), the order of the various frequencies being randomly determined.
      Furthermore, to test the reproducibility, a repeat measurement of PWV was
      obtained in one randomly selected frequency. Blood pressure (BP) was measured by
      conventional means at each pacing frequency. PWV appeared fairly reproducible
      because no significant difference was disclosed between the 2 measurements
      obtained at the same HR level (P=0.5) and both measurements were strongly
      correlated (r=0.87, P<0.001). No significant BP variation was observed during
      pacing. There was a highly significant effect of HR on PWV estimated by a one
      way, within-subjects analysis of variance (P=0.01). This study demonstrates that
      HR is an important factor in the intraindividual variation of PWV in elderly
      subjects. This raises methodological concern about the measurement of this
      parameter. Standardizing PWV for HR level seems mandatory if one wants to
      interpret PWV changes in clinical trials or in the follow-up of patients.

PMID- 12052847
TI  - Nitric oxide modulates superoxide release and peroxynitrite formation in human
      blood vessels.
AB  - Nitric oxide and superoxide have important roles as vascular signaling molecules.
      Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite. The
      relative balance between these radicals has important implications for vascular
      pathophysiology in hypertension and other vascular disease states. However, the
      relationships between superoxide, NO, and peroxynitrite formation in human blood
      vessels remain unclear. Accordingly, we systematically measured NO, superoxide,
      and peroxynitrite production from human internal mammary arteries, radial
      arteries, and saphenous veins from 78 patients undergoing coronary bypass
      surgery. Basal superoxide release was detected in all vessels at similar levels.
      However, endothelial removal or nitric oxide synthase inhibition increased mean
      superoxide release, with a corresponding reduction in peroxynitrite formation.
      Conversely, NO donors and superoxide scavengers both reduced superoxide release,
      whereas only NO donors increased peroxynitrite formation. These changes were much
      larger in arteries that in veins, but there were striking correlations between
      superoxide production, NO bioavailability, and peroxynitrite formation between
      the vessel types. Our findings provide direct evidence for coordinated vascular
      signaling mediated by interactions between NO, superoxide, and peroxynitrite and
      have important implications for studies of the functional effects of these
      radicals in human blood vessels.

PMID- 12052848
TI  - KDR (VEGF receptor 2) is the major mediator for the hypotensive effect of VEGF.
AB  - Vascular endothelial growth factor (VEGF) exerts vasodilation-induced hypotension
      as a major side effect for treatment of ischemic diseases. VEGF has 2 receptor
      tyrosine kinases, KDR and Flt-1. Little is known about which receptor mediates
      VEGF-induced hypotension. To elucidate the role of each receptor in mediating
      hypotension, KDR-selective and Flt-1-selective mutants were used for in vitro and
      in vivo studies. The KDR-selective mutant induced vascular endothelial cell
      proliferation comparable to VEGF, whereas the Flt-1- selective mutant had no
      effect on proliferation. Intravenous injection of KDR-selective mutant, Flt
      selective mutant, or VEGF caused a dose-related decrease in mean arterial
      pressure in conscious rats. The hypotensive response to KDR-selective mutant was
      significantly less than that to VEGF (P<0.01) but was greater than that to Flt
      selective mutant (P<0.01). Similarly, VEGF and KDR-selective mutant induced more
      potent vasorelaxation than Flt-selective mutant or placenta growth factor that
      binds Flt-1 only (P<0.01), and the vasorelaxation to KDR-selective mutant was not
      significantly different at low concentrations but less than that to VEGF at high
      concentrations. The results indicate that the vasodilation and hypotensive effect
      of VEGF may involve both receptors, but KDR is the predominant receptor mediating
      this effect. Because KDR-selective mutant induced proliferation and angiogenesis
      similar to VEGF but was associated with 36% attenuation in hypotension, the data
      suggest that the KDR-selective mutant may represent an alternative treatment for
      ischemic diseases.

PMID- 12052850
TI  - Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking.
AB  - The purpose of this study was to compare circadian blood pressure and heart rate
      patterns and other cardiovascular effects of nicotine delivered rapidly (via
      nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking
      (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve
      healthy cigarette smokers were studied on a research ward when they smoked
      cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or
      placebo NNS, each for 5 days. There were no significant differences in systolic
      blood pressure, but diastolic blood pressure was slightly increased during
      cigarette smoking. Plasma epinephrine, beta-thromboglobulin, and fibrinogen
      levels were higher during cigarette smoking than with TDN. For most measurements,
      NNS values were intermediate between and not significantly different from those
      of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS
      have fewer effects on biomarkers of cardiovascular risk than does cigarette
      smoking.

PMID- 12052849
TI  - Losartan reduces central and peripheral sympathetic nerve activity in a rat model
      of neurogenic hypertension.
AB  - We have developed a new model of neurogenic hypertension in the rat, in which
      hypertension is caused by injecting 50 microL of 10% phenol in the lower pole of
      one kidney. Administration of phenol in the kidney causes an immediate and
      persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the
      posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA).
      Because angiotensin II (Ang II) is known to stimulate central and peripheral
      sympathetic nervous system (SNS) activity, we have tested the hypothesis that
      losartan, a specific Ang II AT1 receptor antagonist, may lower BP, at least in
      part, by SNS inhibition. To this end, we studied the effects of losartan on BP
      and SNS activity following intrarenal phenol injection. Central SNS activity was
      measured by NE secretion from the PH using a microdialysis technique, and
      peripheral SNS activity was measured by direct recording of renal nerve activity.
      At the end of the experiments, brains were isolated and interleukin (IL)-1beta
      and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in
      the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal
      injection of phenol raised BP, as well as central and renal SNS activity, but
      reduced the abundance of IL-1beta and neuronal NOS (nNOS) mRNA in the PH, PVN,
      and LC. Whether injected intravenously or in the lateral ventricle, losartan
      caused a significant (P<0.01) and dose-dependent inhibition of the effects of
      phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a
      significant (P<0.01) and dose-dependent rise in IL-1beta and nNOS-mRNA gene
      expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these
      studies have shown that the intrarenal injection of phenol causes a rise in
      central and renal SNS activity and a decrease in IL-1beta and nNOS-mRNA in the
      PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as
      the decrease in IL-1beta and nNOS mRNA abundance caused by phenol. These studies
      have demonstrated that the antihypertensive action of losartan in the phenol
      renal injury model is largely mediated by inhibition of central and peripheral
      SNS activity and suggest that activation of IL-1beta and nNOS, 2 important
      modulators of central SNS activity, mediates the inhibitory action of losartan on
      SNS activity.

PMID- 12052851
TI  - Prediction of outcomes in hypertensive patients with suspected coronary disease.
AB  - Stress echocardiography has been shown to improve the diagnosis of coronary
      artery disease in the presence of hypertension, but its value in prognostic
      evaluation is unclear. We sought to determine whether stress echocardiography
      could be used to predict mortality in 2363 patients with hypertension, who were
      followed for up to 10 years (mean 4.0+/-1.8) for death and revascularization.
      Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left
      ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were
      confined to one territory in 489 patients (21%) and to multiple territories in
      365 patients (15%). Cardiac death was less frequent among the patients able to
      exercise than among those undergoing dobutamine echocardiography (4% versus 7%,
      P< 0.001). The risk of death in patients with a negative stress echocardiogram
      was <1% per year. Ischemia identified by stress echocardiography was an
      independent predictor of mortality in those able to exercise (hazard ratio 2.21,
      95% confidence intervals 1.10 to 4.43, P=0.0001) as well as those undergoing
      dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75,
      P=0.0001); other predictors were age, heart failure, resting LV dysfunction, and
      the Duke treadmill score. In stepwise models replicating the sequence of clinical
      evaluation, the results of stress echocardiography added prognostic power to
      models based on clinical and stress-testing variables. Thus, the results of
      stress echocardiography are an independent predictor of cardiac death in
      hypertensive patients with known or suspected coronary artery disease,
      incremental to clinical risks and exercise results.

PMID- 12052852
TI  - Socioeconomic inequalities in hypertension prevalence and care: the IHPAF Study.
AB  - To analyze the health disparities relative to the prevalence of arterial
      hypertension and its therapeutic control in the active French population, in
      relation to occupational categories (OC), a population of 17 359 men and 12 267
      women was assessed from January 1997 to April 1998. The initial phase was a cross
      sectional analysis of a cohort study designed to assess the incidence of arterial
      hypertension in a French working population. Information was collected by the
      worksite physician during the annual examination. Blood pressure (BP) was
      measured using a validated automatic device. Among subjects with a BP > or
      =140/90 mm Hg, patients not treated with antihypertensive drugs were invited to
      have an additional BP measurement, 1 month later. Overall prevalence was 16.1%
      for men and 9.4% for women. Both prevalence and therapeutic control of high BP
      were related to OCs in this study. Prevalence of hypertension was higher and
      maintenance of therapeutic control lower among lower OCs. In contrast, awareness
      of high BP and the proportion of hypertensive subjects under current treatment
      were not related to OCs. Educational level and low OC were significantly related
      to prevalence of high BP after adjustment for obesity, excessive alcohol
      consumption, and sedentary lifestyle in women only. A poor BP control under
      treatment was related to high alcohol intake and low OC in men. In women only,
      however, low educational level was related to high prevalence of hypertension and
      poor BP control under antihypertensive treatment. Inequalities in hypertension
      prevalence persist, with prevalence being higher among lower OCs. Social
      disparities were not observed, however, in awareness of their condition among
      hypertensive subjects and among patients for receiving versus not receiving any
      treatment for hypertension. In contrast, BP control under antihypertensive
      treatment was lower among lower OCs.

PMID- 12052854
TI  - Renin-angiotensin and kallikrein-kinin systems coordinately modulate
      angiogenesis.

PMID- 12052855
TI  - Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway.
AB  - The EGF-CFC gene Cripto encodes an extracellular protein that has been implicated
      in the signaling pathway for the transforming growth factor beta (TGF beta)
      ligand Nodal. Although recent findings in frog and fish embryos have suggested
      that EGF-CFC proteins function as coreceptors for Nodal, studies in cell culture
      have implicated Cripto as a growth factor-like signaling molecule. Here we
      reconcile these apparently disparate models of Cripto function by using a
      mammalian cell culture assay to investigate the signaling activities of Nodal and
      EGF-CFC proteins. Using a luciferase reporter assay, we found that Cripto has
      activities consistent with its being a coreceptor for Nodal. However, Cripto can
      also function as a secreted signaling factor in cell coculture assays, suggesting
      that it may also act as a coligand for Nodal. Furthermore, we found that the
      ability of Cripto to bind to Nodal and mediate Nodal signaling requires the
      addition of an O-linked fucose monosaccharide to a conserved site within EGF-CFC
      proteins. We propose a model in which Cripto has dual roles as a coreceptor as
      well as a coligand for Nodal and that this signaling interaction with Nodal is
      regulated by an unusual form of glycosylation. Our findings highlight the
      significance of extracellular modulation of ligand activity as an important means
      of regulating TGF beta signaling pathways during vertebrate development.

PMID- 12052856
TI  - Acetylation of nucleosomal histones by p300 facilitates transcription from tax
      responsive human T-cell leukemia virus type 1 chromatin template.
AB  - Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the
      viral transcriptional activator Tax. Tax activates viral transcription through
      interaction with the cellular transcription factor CREB and the coactivators
      CBP/p300. One key property of the coactivators is the presence of histone
      acetyltransferase (HAT) activity, which enables p300/CBP to modify nucleosome
      structure. The data presented in this manuscript demonstrate that full-length
      p300 and CBP facilitate transcription of a reconstituted chromatin template in
      the presence of Tax and CREB. The ability of p300 and CBP to activate
      transcription from the chromatin template is dependent upon the HAT activity.
      Moreover, the coactivator HAT activity must be tethered to the template by Tax
      and CREB, since a p300 mutant that fails to interact with Tax did not facilitate
      transcription or acetylate histones. p300 acetylates histones H3 and H4 within
      nucleosomes located in the promoter and 5' proximal regions of the template.
      Nucleosome acetylation is accompanied by an increase in the level of binding of
      RNA polymerase II transcription factor TFIID and RNA polymerase II to the
      promoter. Interestingly, we found distinct transcriptional activities between CBP
      and p300. CBP, but not p300, possesses an N-terminal activation domain which
      directly activates Tax-mediated HTLV-1 transcription from a naked DNA template.
      Finally, using the chromatin immunoprecipitation assay, we provide the first
      direct experimental evidence that p300 and CBP are associated with the HTLV-1
      long terminal repeat in vivo.

PMID- 12052857
TI  - Transferable domain in the G(1) cyclin Cln2 sufficient to switch degradation of
      Sic1 from the E3 ubiquitin ligase SCF(Cdc4) to SCF(Grr1).
AB  - Degradation of Saccharomyces cerevisiae G(1) cyclins Cln1 and Cln2 is mediated by
      the ubiquitin-proteasome pathway and involves the SCF E3 ubiquitin-ligase complex
      containing the F-box protein Grr1 (SCF(Grr1)). Here we identify the domain of
      Cln2 that confers instability and describe the signals in Cln2 that result in
      binding to Grr1 and rapid degradation. We demonstrate that mutants of Cln2 that
      lack a cluster of four Cdc28 consensus phosphorylation sites are highly
      stabilized and fail to interact with Grr1 in vivo. Since one of the
      phosphorylation sites lies within the Cln2 PEST motif, a sequence rich in
      proline, aspartate or glutamate, serine, and threonine residues found in many
      unstable proteins, we fused various Cln2 C-terminal domains containing
      combinations of the PEST and the phosphoacceptor motifs to stable reporter
      proteins. We show that fusion of the Cln2 domain to a stabilized form of the
      cyclin-dependent kinase inhibitor Sic1 (Delta N-Sic1), a substrate of SCF(Cdc4),
      results in degradation in a phosphorylation-dependent manner. Fusion of Cln2
      degradation domains to Delta N-Sic1 switches degradation of Sic1 from SCF(Cdc4)
      to SCF(Grr1). Delta N-Sic1 fused with a Cln2 domain containing the PEST motif and
      four phosphorylation sites binds to Grr1 and is unstable and ubiquitinated in
      vivo. Interestingly, the phosphoacceptor domain of Cln2 binds to Grr1 but is not
      ubiquitinated and is stable. In summary, we have identified a small transferable
      domain in Cln2 that can redirect a stabilized SCF(Cdc4) target for SCF(Grr1)
      mediated degradation by the ubiquitin-proteasome pathway.

PMID- 12052859
TI  - Mouse model for human arginase deficiency.
AB  - Deficiency of liver arginase (AI) causes hyperargininemia (OMIM 207800), a
      disorder characterized by progressive mental impairment, growth retardation, and
      spasticity and punctuated by sometimes fatal episodes of hyperammonemia. We
      constructed a knockout mouse strain carrying a nonfunctional AI gene by
      homologous recombination. Arginase AI knockout mice completely lacked liver
      arginase (AI) activity, exhibited severe symptoms of hyperammonemia, and died
      between postnatal days 10 and 14. During hyperammonemic crisis, plasma ammonia
      levels of these mice increased >10-fold compared to those for normal animals.
      Livers of AI-deficient animals showed hepatocyte abnormalities, including cell
      swelling and inclusions. Plasma amino acid analysis showed the mean arginine
      level in knockouts to be approximately fourfold greater than that for the wild
      type and threefold greater than that for heterozygotes; the mean proline level
      was approximately one-third and the ornithine level was one-half of the proline
      and ornithine levels, respectively, for wild-type or heterozygote mice-
      understandable biochemical consequences of arginase deficiency. Glutamic acid,
      citrulline, and histidine levels were about 1.5-fold higher than those seen in
      the phenotypically normal animals. Concentrations of the branched-chain amino
      acids valine, isoleucine, and leucine were 0.4 to 0.5 times the concentrations
      seen in phenotypically normal animals. In summary, the AI-deficient mouse
      duplicates several pathobiological aspects of the human condition and should
      prove to be a useful model for further study of the disease mechanism(s) and to
      explore treatment options, such as pharmaceutical administration of sodium
      phenylbutyrate and/or ornithine and development of gene therapy protocols.

PMID- 12052858
TI  - A conserved domain of Schizosaccharomyces pombe dfp1(+) is uniquely required for
      chromosome stability following alkylation damage during S phase.
AB  - The fission yeast Dbf4 homologue Dfp1 has a well-characterized role in regulating
      the initiation of DNA replication. Sequence analysis of Dfp1 homologues reveals
      three highly conserved regions, referred to as motifs N, M, and C. To determine
      the roles of these conserved regions in Dfp1 function, we have generated dfp1
      alleles with mutations in these regions. Mutations in motif N render cells
      sensitive to a broad range of DNA-damaging agents and replication inhibitors, yet
      these mutant proteins are efficient activators of Hsk1 kinase in vitro. In
      contrast, mutations in motif C confer sensitivity to the alkylating agent methyl
      methanesulfonate (MMS) but, surprisingly, not to UV, ionizing radiation, or
      hydroxyurea. Motif C mutants are poor activators of Hsk1 in vitro but can fulfill
      the essential function(s) of Dfp1 in vivo. Strains carrying dfp1 motif C mutants
      have an intact mitotic and intra-S-phase checkpoint, and epistasis analysis
      indicates that dfp1 motif C mutants function outside of the known MMS damage
      repair pathways, suggesting that the observed MMS sensitivity is due to defects
      in recovery from DNA damage. The motif C mutants are most sensitive to MMS during
      S phase and are partially suppressed by deletion of the S-phase checkpoint kinase
      cds1. Following treatment with MMS, dfp1 motif C mutants exhibit nuclear
      fragmentation, chromosome instability, precocious recombination, and persistent
      checkpoint activation. We propose that Dfp1 plays at least two genetically
      separable roles in the DNA damage response in addition to its well-characterized
      role in the initiation of DNA replication and that motif C plays a critical role
      in the response to alkylation damage, perhaps by restarting or stabilizing
      stalled replication forks.

PMID- 12052860
TI  - Generation of multiple isoforms of eukaryotic translation initiation factor 4GI
      by use of alternate translation initiation codons.
AB  - Eukaryotic translation initiation factor 4GI (eIF4GI) is an essential protein
      that is the target for translational regulation in many cellular processes and
      viral systems. It has been shown to function in both cap-dependent and cap
      independent translation initiation by recruiting the 40S ribosomal subunit to the
      mRNA cap structure or internal ribosome entry site (IRES) element, respectively.
      Interestingly eIF4GI mRNA itself has been reported to contain an IRES element in
      its 5' end that facilitates eIF4GI protein synthesis via a cap-independent
      mechanism. In HeLa cells, eIF4GI exists as several isoforms that differ in their
      migration in sodium dodecyl sulfate (SDS) gels; however, the nature of these
      isoforms was unclear. Here, we report a new cDNA clone for eIF4GI that extends
      the 5' sequence 340 nucleotides beyond the previously published sequence. The new
      extended sequence of eIF4GI is located on chromosome 3, within two additional
      exons immediately upstream of the previously published eIF4GI sequence. When mRNA
      transcribed from this cDNA clone was translated in vitro, five eIF4GI
      polypeptides were generated that comigrated in SDS-polyacrylamide gels with the
      five isoforms of native eIF4GI. Furthermore, translation of eIF4GI-enhanced green
      fluorescent protein fusion constructs in vitro or in vivo generated five isoforms
      of fusion polypeptides, suggesting that multiple isoforms of eIF4GI are generated
      by alternative translation initiation in vitro and in vivo. Mutation of two of
      the five in-frame AUG residues in the eIF4GI cDNA sequence resulted in loss of
      corresponding polypeptides after translation in vitro, confirming alternate use
      of AUGs as the source of the multiple polypeptides. The 5' untranslated region of
      eIF4GI mRNA also contains an out-of-frame open reading frame (ORF) that may down
      regulate expression of eIF4GI. Further, data are presented to suggest that a
      proposed IRES embedded in the eIF4GI ORF is able to catalyze synthesis of
      multiple eIF4GI isoforms as well. Our data suggest that expression of the eIF4GI
      isoforms is partly controlled by a complex translation strategy involving both
      cap-dependent and cap-independent mechanisms.

PMID- 12052861
TI  - Recombinational telomere elongation promoted by DNA circles.
AB  - Yeast mutants lacking telomerase are capable of maintaining telomeres by an
      alternate mechanism that depends on homologous recombination. We show here, by
      using Kluyveromyces lactis cells containing two types of telomeric repeats, that
      recombinational telomere elongation generates a repeating pattern common in most
      or all telomeres in survivors that retain both repeat types. We propose that
      these patterns arise from small circles of telomeric DNA being used as templates
      for rolling-circle gene conversion and that the sequence from the lengthened
      telomere is spread to other telomeres by additional, more typical gene conversion
      events. Consistent with this, artificially constructed circles of DNA containing
      telomeric repeats form long tandem arrays at telomeres when transformed into K.
      lactis cells. Mixing experiments done with two species of telomeric circles
      indicated that all of the integrated copies of the transforming sequence arise
      from a single original circular molecule.

PMID- 12052863
TI  - c-Src-mediated phosphorylation of hnRNP K drives translational activation of
      specifically silenced mRNAs.
AB  - hnRNPK and hnRNP E1/E2 mediate translational silencing of cellular and viral
      mRNAs in a differentiation-dependent way by binding to specific regulatory
      sequences. The translation of 15-lipoxygenase (LOX) mRNA in erythroid precursor
      cells and of the L2 mRNA of human papilloma virus type 16 (HPV-16) in squamous
      epithelial cells is silenced when either of these cells is immature and is
      activated in maturing cells by unknown mechanisms. Here we address the question
      of how the silenced mRNA can be translationally activated. We show that hnRNP K
      and the c-Src kinase specifically interact with each other, leading to c-Src
      activation and tyrosine phosphorylation of hnRNP K in vivo and in vitro. c-Src
      mediated phosphorylation reversibly inhibits the binding of hnRNP K to the
      differentiation control element (DICE) of the LOX mRNA 3' untranslated region in
      vitro and specifically derepresses the translation of DICE-bearing mRNAs in vivo.
      Our results establish a novel role of c-Src kinase in translational gene
      regulation and reveal a mechanism by which silenced mRNAs can be translationally
      activated.

PMID- 12052862
TI  - Retinoic acid receptors inhibit AP1 activation by regulating extracellular signal
      regulated kinase and CBP recruitment to an AP1-responsive promoter.
AB  - Retinoids exhibit antineoplastic activities that may be linked to retinoid
      receptor-mediated transrepression of activating protein 1 (AP1), a heterodimeric
      transcription factor composed of fos- and jun-related proteins. Here we show that
      transcriptional activation of an AP1-regulated gene through the mitogen-activated
      protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway
      (MAPK(ERK)) is characterized, in intact cells, by a switch from a fra2-junD dimer
      to a junD-fosB dimer loading on its promoter and by simultaneous recruitment of
      ERKs, CREB-binding protein (CBP), and RNA polymerase II. All-trans-retinoic acid
      (atRA) receptor (RAR) was tethered constitutively to the AP1 promoter. AP1
      transrepression by retinoic acid was concomitant to glycogen synthase kinase 3
      activation, negative regulation of junD hyperphosphorylation, and to decreased
      RNA polymerase II recruitment. Under these conditions, fra1 loading to the AP1
      response element was strongly increased. Importantly, CBP and ERKs were excluded
      from the promoter in the presence of atRA. AP1 transrepression by retinoids was
      RAR and ligand dependent, but none of the functions required for RAR-mediated
      transactivation was necessary for AP1 transrepression. These results indicate
      that transrepressive effects of retinoids are mediated through a mechanism
      unrelated to transcriptional activation, involving the RAR-dependent control of
      transcription factors and cofactor assembly on AP1-regulated promoters.

PMID- 12052864
TI  - Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain
      and GADD45 binding.
AB  - A variety of cellular stresses activate the stress-responsive mitogen-activated
      protein (MAP) kinases p38 and JNK. In this study, we studied the activation
      mechanism of a human MAP kinase kinase kinase, MTK1 (also known as MEKK4), which
      mediates activation of both p38 and JNK. MTK1 has an extensive N-terminal
      noncatalytic domain composed of approximately 1,300 amino acids. Full-length or
      near full-length MTK1 is catalytically inactive when expressed in Saccharomyces
      cerevisiae cells, as it is in mammalian cells. Deletion of a segment including
      positions 253 to 553 activates kinase, indicating that this segment contains the
      autoinhibitory domain. In the autoinhibited conformation, the MTK1 kinase domain
      cannot interact with its substrate, MKK6. By a functional complementation
      screening with yeast cells, GADD45 proteins (GADD45alpha, beta, and gamma) were
      identified as MTK1 activators. GADD45 proteins bind a site in MTK1 near the
      inhibitory domain and relieve autoinhibition. Mutants of full-length MTK1 were
      isolated that can interact with MKK6 in the absence of the activator GADD45
      proteins. These MTK1 mutants are constitutively active, in both yeast and
      mammalian cells. A model of MTK1 autoinhibition by the N-terminal inhibitory
      domain and activation by GADD45 binding is presented.

PMID- 12052865
TI  - Increased p300 expression inhibits glucocorticoid receptor-T-cell receptor
      antagonism but does not affect thymocyte positive selection.
AB  - Positive selection of T cells is postulated to be dependent on the
      counterinteraction between glucocorticoid receptor (GR)- and T-cell-receptor
      (TCR)-induced death signals. In this study we used T-cell-specific expression of
      p300 to investigate whether GR-TCR cross talk between thymocytes was affected.
      Activation of the p300-transgenic T cells led to enhanced thymocyte proliferation
      and increased interleukin 2 production. Thymocyte death, induced by TCR
      engagement, was no longer prevented by dexamethasone in p300-transgenic mice,
      indicating an absence of GR-TCR cross-inhibition. This was accompanied by a 50%
      reduction in the number of thymocytes in p300-transgenic mice. However, the
      CD4/CD8 profile of thymocytes remained unchanged in p300-transgenic mice. There
      was no effect on positive selection of the bulk thymocytes or thymocytes with
      transgenic TCR in p300-transgenic mice. In addition, there was no apparent TCR
      repertoire "hole" in the selected antigens examined. Our results illustrate a
      critical role of CBP/p300 in thymic GR-TCR counterinteraction yet do not support
      the involvement of GR-TCR antagonism in thymocyte positive selection.

PMID- 12052866
TI  - SOCS-6 binds to insulin receptor substrate 4, and mice lacking the SOCS-6 gene
      exhibit mild growth retardation.
AB  - SOCS-6 is a member of the suppressor of cytokine signaling (SOCS) family of
      proteins (SOCS-1 to SOCS-7 and CIS) which each contain a central SH2 domain and a
      carboxyl-terminal SOCS box. SOCS-1, SOCS-2, SOCS-3, and CIS act to negatively
      regulate cytokine-induced signaling pathways; however, the actions of SOCS-4,
      SOCS-5, SOCS-6, and SOCS-7 remain less clear. Here we have used both biochemical
      and genetic approaches to examine the action of SOCS-6. We found that SOCS-6 and
      SOCS-7 are expressed ubiquitously in murine tissues. Like other SOCS family
      members, SOCS-6 binds to elongins B and C through its SOCS box, suggesting that
      it might act as an E3 ubiquitin ligase that targets proteins bound to its SH2
      domain for ubiquitination and proteasomal degradation. We investigated the
      binding specificity of the SOCS-6 and SOCS-7 SH2 domains and found that they
      preferentially bound to phosphopeptides containing a valine in the
      phosphotyrosine (pY) +1 position and a hydrophobic residue in the pY +2 and pY +3
      positions. In addition, these SH2 domains interacted with a protein complex
      consisting of insulin receptor substrate 4 (IRS-4), IRS-2, and the p85 regulatory
      subunit of phosphatidylinositol 3-kinase. To investigate the physiological role
      of SOCS-6, we generated mice lacking the SOCS-6 gene. SOCS-6(-/-) mice were born
      in a normal Mendelian ratio, were fertile, developed normally, and did not
      exhibit defects in hematopoiesis or glucose homeostasis. However, both male and
      female SOCS-6(-/-) mice weighed approximately 10% less than wild-type
      littermates.

PMID- 12052867
TI  - Characterization of specific protein-RNA complexes associated with the coupling
      of polyadenylation and last-intron removal.
AB  - Polyadenylation and splicing are highly coordinated on substrate RNAs capable of
      coupled polyadenylation and splicing. Individual elements of both splicing and
      polyadenylation signals are required for the in vitro coupling of the processing
      reactions. In order to understand more about the coupling mechanism, we examined
      specific protein-RNA complexes formed on RNA substrates, which undergo coupled
      splicing and polyadenylation. We hypothesized that formation of a coupling
      complex would be adversely affected by mutations of either splicing or
      polyadenylation elements known to be required for coupling. We defined three
      specific complexes (A(C)', A(C), and B(C)) that form rapidly on a coupled
      splicing and polyadenylation substrate, well before the appearance of spliced
      and/or polyadenylated products. The A(C)' complex is formed by 30 s after mixing,
      the A(C) complex is formed between 1 and 2 min after mixing, and the B(C) complex
      is formed by 2 to 3 min after mixing. A(C)' is a precursor of A(C), and the A(C)'
      and/or A(C) complex is a precursor of B(C). Of the three complexes, B(C) appears
      to be a true coupling complex in that its formation was consistently diminished
      by mutations or experimental conditions known to disrupt coupling. The
      characteristics of the A(C)' complex suggest that it is analogous to the
      spliceosomal A complex, which forms on splicing-only substrates. Formation of the
      A(C)' complex is dependent on the polypyrimidine tract. The transition from A(C)'
      to A(C) appears to require an intact 3'-splice site. Formation of the B(C)
      complex requires both splicing elements and the polyadenylation signal. A unique
      polyadenylation-specific complex formed rapidly on substrates containing only the
      polyadenylation signal. This complex, like the A(C)' complex, formed very
      transiently on the coupled splicing and polyadenylation substrate; we suggest
      that these two complexes coordinate, resulting in the B(C) complex. We also
      suggest a model in which the coupling mechanism may act as a dominant checkpoint
      in which aberrant definition of one exon overrides the normal processing at
      surrounding wild-type sites.

PMID- 12052868
TI  - Cell attachment to the extracellular matrix induces proteasomal degradation of
      p21(CIP1) via Cdc42/Rac1 signaling.
AB  - The cyclin-dependent kinase 2 (Cdk2) inhibitors p21(CIP1) and p27(KIP1) are
      negatively regulated by anchorage during cell proliferation, but it is unclear
      how integrin signaling may affect these Cdk2 inhibitors. Here, we demonstrate
      that integrin ligation led to rapid reduction of p21(CIP1) and p27(KIP1) protein
      levels in three distinct cell types upon attachment to various extracellular
      matrix (ECM) proteins, including fibronectin (FN), or to immobilized agonistic
      anti-integrin monoclonal antibodies. Cell attachment to FN did not rapidly
      influence p21(CIP1) mRNA levels, while the protein stability of p21(CIP1) was
      decreased. Importantly, the down-regulation of p21(CIP1) and p27(KIP1) was
      completely blocked by three distinct proteasome inhibitors, demonstrating that
      integrin ligation induced proteasomal degradation of these Cdk2 inhibitors.
      Interestingly, ECM-induced proteasomal proteolysis of a ubiquitination-deficient
      p21(CIP1) mutant (p21K6R) also occurred, showing that the proteasomal degradation
      of p21(CIP1) was ubiquitin independent. Concomitant with our finding that the
      small GTPases Cdc42 and Rac1 were activated by attachment to FN, constitutively
      active (ca) Cdc42 and ca Rac1 promoted down-regulation of p21(CIP1). However,
      dominant negative (dn) Cdc42 and dn Rac1 mutants blocked the anchorage-induced
      degradation of p21(CIP1), suggesting that an integrin-induced Cdc42/Rac1
      signaling pathway activates proteasomal degradation of p21(CIP1). Our results
      indicate that integrin-regulated proteasomal proteolysis might contribute to
      anchorage-dependent cell cycle control.

PMID- 12052869
TI  - Two ras pathways in fission yeast are differentially regulated by two ras guanine
      nucleotide exchange factors.
AB  - How a given Ras prreotein coordinates multiple signaling inputs and outputs is a
      fundamental issue of signaling specificity. Schizosaccharomyces pombe contains
      one Ras, Ras1, that has two distinct outputs. Ras1 activates Scd1, a presumptive
      guanine nucleotide exchange factor (GEF) for Cdc42, to control morphogenesis and
      chromosome segregation, and Byr2, a component of a mitogen-activated protein
      kinase cascade, to control mating. So far there is only one established Ras1 GEF,
      Ste6. Paradoxically, ste6 null (ste6 Delta) mutants are sterile but normal in
      cell morphology. This suggests that Ste6 specifically activates the Ras1-Byr2
      pathway and that there is another GEF capable of activating the Scd1 pathway. We
      thereby characterized a potential GEF, Efc25. Genetic data place Efc25 upstream
      of the Ras1-Scd1, but not the Ras1-Byr2, pathway. Like ras1 Delta and scd1 Delta,
      efc25 Delta is synthetically lethal with a deletion in tea1, a critical element
      for cell polarity control. Using truncated proteins, we showed that the C
      terminal GEF domain of Efc25 is essential for function and regulated by the N
      terminus. We conclude that Efc25 acts as a Ras1 GEF specific for the Scd1
      pathway. While ste6 expression is induced during mating, efc25 expression is
      constitutive. Moreover, Efc25 overexpression renders cells hyperelongated and
      sterile; the latter can be rescued by activated Ras1. This suggests that Efc25
      can recruit Ras1 to selectively activate Scd1 at the expense of Byr2.
      Reciprocally, Ste6 overexpression can block Scd1 activation. We propose that
      external signals can partly segregate two Ras1 pathways by modulating GEF
      expression and that GEFs can influence how Ras is coupled to specific effectors.

PMID- 12052870
TI  - Interactions of the Mcm1 MADS box protein with cofactors that regulate mating in
      yeast.
AB  - The yeast Mcm1 protein is a member of the MADS box family of transcriptional
      regulatory factors, a class of DNA-binding proteins that control numerous
      cellular and developmental processes in yeast, Drosophila melanogaster, plants,
      and mammals. Although these proteins bind DNA on their own, they often combine
      with different cofactors to bind with increased affinity and specificity to their
      target sites. To understand how this class of proteins functions, we have made a
      series of alanine substitutions in the MADS box domain of Mcm1 and examined the
      effects of these mutations in combination with its cofactors that regulate mating
      in yeast. Our results indicate which residues of Mcm1 are essential for viability
      and transcriptional regulation with its cofactors in vivo. Most of the mutations
      in Mcm1 that are lethal affect DNA-binding affinity. Interestingly, the lethality
      of many of these mutations can be suppressed if the MCM1 gene is expressed from a
      high-copy-number plasmid. Although many of the alanine substitutions affect the
      ability of Mcm1 to activate transcription alone or in combination with the alpha
      1 and Ste12 cofactors, most mutations have little or no effect on Mcm1-mediated
      repression in combination with the alpha 2 cofactor. Even nonconservative amino
      acid substitutions of residues in Mcm1 that directly contact alpha 2 do not
      significantly affect repression. These results suggest that within the same
      region of the Mcm1 MADS box domain, there are different requirements for
      interaction with alpha 2 than for interaction with either alpha1 or Ste12. Our
      results suggest how a small domain, the MADS box, interacts with multiple
      cofactors to achieve specificity in transcriptional regulation and how subtle
      differences in the sequences of different MADS box proteins can influence the
      interactions with specific cofactors while not affecting the interactions with
      common cofactors.

PMID- 12052871
TI  - Phosphorylation of the RNA polymerase II carboxyl-terminal domain by CDK9 is
      directly responsible for human immunodeficiency virus type 1 Tat-activated
      transcriptional elongation.
AB  - Stimulation of transcriptional elongation by the human immunodeficiency virus
      type 1 Tat protein is mediated by CDK9, a kinase that phosphorylates the RNA
      polymerase II carboxyl-terminal domain (CTD). In order to obtain direct evidence
      that this phosphorylation event can alter RNA polymerase processivity, we
      prepared transcription elongation complexes that were arrested by the lac
      repressor. The CTD was then dephosphorylated by treatment with protein
      phosphatase 1. The dephosphorylated transcription complexes were able to resume
      the transcription elongation when IPTG (isopropyl-beta-D-thiogalactopyranoside)
      and nucleotides were added to the reaction. Under these chase conditions,
      efficient rephosphorylation of the CTD was observed in complexes containing the
      Tat protein but not in transcription complexes prepared in the absence of Tat
      protein. Immunoblots and kinase assays with synthetic peptides showed that Tat
      activated CDK9 directly since the enzyme and its cyclin partner, cyclin T1, were
      present at equivalent levels in transcription complexes prepared in the presence
      or absence of Tat. Chase experiments with the dephosphorylated elongation
      transcription complexes were performed in the presence of the CDK9 kinase
      inhibitor DRB (5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole). Under these
      conditions there was no rephosphorylation of the CTD during elongation, and
      transcription through either a stem-loop terminator or bent DNA arrest sequence
      was strongly inhibited. In experiments in which the CTD was phosphorylated prior
      to elongation, the amount of readthrough of the terminator sequences was
      proportional to the extent of the CTD modification. The change in processivity is
      due to CTD phosphorylation alone, since even after the removal of Spt5, the
      second substrate for CDK9, RNA polymerase elongation is enhanced by Tat-activated
      CDK9 activity. We conclude that phosphorylation of the RNA polymerase II CTD by
      CDK9 enhances transcription elongation directly.

PMID- 12052872
TI  - Conditional derepression of ferritin synthesis in cells expressing a constitutive
      IRP1 mutant.
AB  - Iron regulatory protein 1 (IRP1), a major posttranscriptional regulator of
      cellular iron and energy metabolism, is controlled by an iron-sulfur cluster
      switch. Cysteine-437 is critical for coordinating the cluster, and its
      replacement yields mutants that do not respond to iron perturbations and
      constitutively bind to cognate mRNA iron-responsive elements (IREs). The
      expression of IRP1(C437S) in cells has been associated with aberrations in iron
      homeostasis and toxicity. We have established clones of human lung (H1299) and
      breast (MCF7) cancer cells that express high levels of IRP1(C437S) in a
      tetracycline-inducible manner. As expected, IRP1(C437S) stabilizes transferrin
      receptor mRNA and inhibits translation of ferritin mRNA in both cell types by
      binding to their respective IREs. However, H1299 transfectants grown at high
      densities are able to overcome the IRP1(C437S)-mediated inhibition in ferritin
      synthesis. The mechanism involves neither alteration in ferritin mRNA levels nor
      utilization of alternative transcription start sites to eliminate the IRE or
      relocate it in less inhibitory downstream positions. The derepression of ferritin
      mRNA translation occurs under conditions where global protein synthesis appears
      to be impaired, as judged by a significant enrichment in the expression of the
      underphosphorylated form of the translational regulator 4E-BP1. Collectively,
      these data document an example where ferritin mRNA translation evades control of
      the IRE-IRP system. The physiological implications of this response are reflected
      in protection against iron-mediated toxicity, oxidative stress, and apoptosis.

PMID- 12052873
TI  - Distinct functions of two RNA ligases in active Trypanosoma brucei RNA editing
      complexes.
AB  - Trypanosome RNA editing is a unique U insertion and U deletion process that
      involves cycles of pre-mRNA cleavage, terminal U addition or U removal, and
      religation. This editing can occur at massive levels and is directed by base
      pairing of trans-acting guide RNAs. Both U insertion and U deletion cycles are
      catalyzed by a single protein complex that contains only seven major proteins,
      band I through band VII. However, little is known about their catalytic
      functions, except that band IV and band V are RNA ligases and genetic analysis
      indicates that the former is important in U deletion. Here we establish
      biochemical approaches to distinguish the individual roles of these ligases,
      based on their distinctive ATP and pyrophosphate utilization. These in vitro
      analyses revealed that both ligases serve in RNA editing. Band V is the RNA
      editing ligase that functions very selectively to seal in U insertion (IREL),
      while band IV is the RNA editing ligase needed to seal in U deletion (DREL). In
      combination with our earlier findings about the cleavage and the U-addition/U
      removal steps of U deletion and U insertion, these results show that all three
      steps of these editing pathways exhibit major differences and suggest that the
      editing complex could have physically separate regions for U deletion and U
      insertion.

PMID- 12052874
TI  - Spermatogenesis and testis development are normal in mice lacking testicular
      orphan nuclear receptor 2.
AB  - Early in vitro cell culture studies suggested that testicular orphan nuclear
      receptor 2 (TR2), a member of the nuclear receptor superfamily, may play
      important roles in the control of several pathways including retinoic acids,
      vitamin D, thyroid hormones, and ciliary neurotrophic factor. Here we report the
      surprising results showing that mice lacking TR2 are viable and have no serious
      developmental defects. Male mice lacking TR2 have functional testes, including
      normal sperm number and motility, and both male and female mice lacking TR2 are
      fertile. In heterozygous TR2(+/-) male mice we found that beta-galactosidase, the
      indicator of TR2 protein expression, was first detected at the age of 3 weeks and
      its expression pattern was restricted mainly in the spermatocytes and round
      spermatids. These protein expression patterns were further confirmed with
      Northern blot analysis of TR2 mRNA expression. Together, results from TR2
      knockout mice suggest that TR2 may not play essential roles in spermatogenesis
      and normal testis development, function, and maintenance. Alternatively, the
      roles of TR2 may be redundant and could be played by other close members of the
      nuclear receptor superfamily such as testicular orphan receptor 4 (TR4) or
      unidentified orphan receptors that share many similar functions with TR2. Further
      studies with double knockouts of both orphan nuclear receptors, TR2 and TR4, may
      reveal their real physiological roles.

PMID- 12052875
TI  - A Functional chromatin domain does not resist X chromosome inactivation:
      silencing of cLys correlates with methylation of a dual promoter-replication
      origin.
AB  - To investigate the molecular mechanism(s) involved in the propagation and
      maintenance of X chromosome inactivation (XCI), the 21.4-kb chicken lysozyme
      (cLys) chromatin domain was inserted into the Hprt locus on the mouse X
      chromosome. The inserted fragment includes flanking matrix attachment regions
      (MARs), an origin of bidirectional replication (OBR), and all the cis-regulatory
      elements required for correct tissue-specific expression of cLys. It also
      contains a recently identified and widely expressed second gene, cGas41. The cLys
      domain is known to function as an autonomous unit resistant to chromosomal
      position effects, as evidenced by numerous transgenic mouse lines showing copy
      number-dependent and development-specific expression of cLys in the myeloid
      lineage. We asked the questions whether this functional chromatin domain was
      resistant to XCI and whether the X inactivation signal could spread across an
      extended region of avian DNA. A generally useful method was devised to generate
      pure populations of macrophages with the transgene either on the active (Xa) or
      the inactive (Xi) chromosome. We found that (i) cLys and cGas41 are expressed
      normally from the Xa; (ii) the cLys chromatin domain, even when bracketed by
      MARs, is not resistant to XCI; (iii) transcription factors are excluded from
      lysozyme enhancers on the Xi; and (iv) inactivation correlates with methylation
      of a CpG island that is both an OBR and a promoter of the cGas41 gene.

PMID- 12052876
TI  - Nucleotide exchange factor for the yeast Hsp70 molecular chaperone Ssa1p.
AB  - We report on the identification of Fes1p (yBR101cp) as a cytosolic homologue of
      Sls1p, an endoplasmic reticulum (ER) protein previously shown to act as a
      nucleotide exchange factor for yeast BiP (M. Kabani, J.-M. Beckerich, and C.
      Gaillardin, Mol. Cell. Biol. 20:6923-6934, 2000). We found that Fes1p associates
      preferentially to the ADP-bound form of the cytosolic Hsp70 molecular chaperone
      Ssa1p and promotes nucleotide release. Fes1p activity was shown to be compartment
      and species specific since Sls1p and Escherichia coli GrpE could not substitute
      for Fes1p. Surprisingly, whereas Sls1p stimulated the ATPase activity of BiP in
      cooperation with luminal J proteins, Fes1p was shown to inhibit the Ydj1p
      mediated activation of Ssa1p ATPase activity in steady-state and single-turnover
      assays. Disruption of FES1 in several wild-type backgrounds conferred a strong
      thermosensitive phenotype but partially rescued ydj1-151 thermosensitivity. The
      Delta fes1 strain was proficient for posttranslational protein translocation, as
      well as for the ER-associated degradation of two substrates. However, the Delta
      fes1 mutant showed increased cycloheximide sensitivity and a general
      translational defect, suggesting that Fes1p acts during protein translation, a
      process in which Ssa1p and Ydj1p are known to be involved. In support of this
      hypothesis, Fes1p was found to be associated with ribosomes.

PMID- 12052877
TI  - Targeting protein phosphatase 1 (PP1) to the actin cytoskeleton: the neurabin
      I/PP1 complex regulates cell morphology.
AB  - Neurabin I, a neuronal actin-binding protein, binds protein phosphatase 1 (PP1)
      and p70 ribosomal S6 protein kinase (p70S6K), both proteins implicated in
      cytoskeletal dynamics. We expressed wild-type and mutant neurabins fused to green
      fluorescent protein in Cos7, HEK293, and hippocampal neurons. Biochemical and
      cellular studies showed that an N-terminal F-actin-binding domain dictated
      neurabin I localization at actin cytoskeleton and promoted disassembly of stress
      fibers. Deletion of the C-terminal coiled-coil and sterile alpha motif domains
      abolished neurabin I dimerization and induced filopodium extension. Immune
      complex assays showed that neurabin I recruited an active PP1 via a PP1-docking
      sequence,(457)KIKF(460). Mutation of the PP1-binding motif or PP1 inhibition by
      okadaic acid and calyculin A abolished filopodia and restored stress fibers in
      cells expressing neurabin I. In vitro and in vivo studies suggested that the
      actin-binding domain attenuated protein kinase A (PKA) phosphorylation of
      neurabin I. Modification of a major PKA site, serine-461, impaired PP1 binding.
      Finally, p70S6K was excluded from neurabin I/PP1 complexes and required the
      displacement of PP1 for recruitment to neurabin I. These studies provided new
      insights into the assembly and regulation of a neurabin I/PP1 complex that
      controls actin rearrangement to promote spine development in mammalian neurons.

PMID- 12052878
TI  - Conserved sequences in a tissue-specific regulatory region of the pdx-1 gene
      mediate transcription in Pancreatic beta cells: role for hepatocyte nuclear
      factor 3 beta and Pax6.
AB  - Pancreas duodenum homeobox 1 (PDX-1) is absolutely required for pancreas
      development and the maintenance of islet beta-cell function. Temporal and cell
      type-specific transcription of the pdx-1 gene is controlled by factors acting
      upon sequences found within its 5'-flanking region. Critical cis-acting
      transcriptional control elements are located within a nuclease hypersensitive
      site that contains three conserved subdomains, termed areas I, II, and III. We
      show that area II acts as a tissue-specific regulatory region of the pdx-1 gene,
      directing transgene expression to a subpopulation of islet cells. Mutation of the
      area II hepatocyte nuclear factor 3 (HNF3) binding element in the larger area I-
      and area II- containing PstBst fragment also decreases PB(hsplacZ) transgene
      penetrance. These two results indicate possible ontogenetic and/or functional
      heterogeneity of the beta-cell population. Several other potential positive- and
      negative-acting control elements were identified in area II after mutation of the
      highly conserved sequence blocks within this subdomain. Pax6, a factor essential
      for islet alpha-cell development and islet hormone gene expression, was shown to
      bind in area II in vitro. Pax6 and HNF3 beta were also found to bind to this
      region in vivo by using the chromatin immunoprecipitation assay. Collectively,
      these data suggest an important role for both HNF3 beta and Pax6 in regulating
      pdx-1 expression in beta cells.

PMID- 12052879
TI  - ErbB2 is required for muscle spindle and myoblast cell survival.
AB  - Signaling mediated by ErbB2 is thought to play a critical role in numerous
      developmental processes. However, due to the embryonic lethality associated with
      the germ line inactivation of erbB2, its role in adult tissues remains largely
      obscure. Given the expression of ErbB2 at the neuromuscular junction, we have
      created a muscle-specific knockout to assess its role there. This resulted in
      viable mice with a progressive defect in proprioception due to loss of muscle
      spindles. Interestingly, a partial reduction of ErbB2 levels also reduced the
      number of muscle spindles. Although histological analysis of the muscle revealed
      an otherwise normal architecture, induction of muscle injury revealed a defect in
      muscle regeneration. Consistent with these observations, primary myoblasts
      lacking ErbB2 exhibit extensive apoptosis upon differentiation into myofibers.
      Taken together, these results illustrate a dual role for ErbB2 in both muscle
      spindle maintenance and survival of myoblasts.

PMID- 12052881
TI  - A third osmosensing branch in Saccharomyces cerevisiae requires the Msb2 protein
      and functions in parallel with the Sho1 branch.
AB  - Two Saccharomyces cerevisiae plasma membrane-spanning proteins, Sho1 and Sln1,
      function during increased osmolarity to activate a mitogen-activated protein
      (MAP) kinase cascade. One of these proteins, Sho1, utilizes the MAP kinase kinase
      kinase Ste11 to activate Pbs2. We previously used the FUS1 gene of the pheromone
      response pathway as a reporter to monitor cross talk in hog1 mutants. Cross talk
      requires the Sho1-Ste11 branch of the HOG pathway, but some residual signaling,
      which is STE11 dependent, still occurs in the absence of Sho1. These observations
      led us to propose the existence of another osmosensor upstream of Ste11. To
      identify such an osmosensor, we screened for mutants in which the residual
      signaling in a hog1 sho1 mutant was further reduced. We identified the MSB2 gene,
      which encodes a protein with a single membrane-spanning domain and a large
      presumptive extracellular domain. Assay of the FUS1-lacZ reporter (in a hog1
      mutant background) showed that sho1 and msb2 mutations both reduced the
      expression of the reporter partially and that the hog1 sho1 msb2 mutant was
      severely defective in the expression of the reporter. The use of DNA microarrays
      to monitor gene expression revealed that Sho1 and Msb2 regulate identical gene
      sets in hog1 mutants. A role for MSB2 in HOG1 strains was also seen in strains
      defective in the two known branches that activate Pbs2: an ssk1 sho1 msb2 strain
      was more osmosensitive than an ssk1 sho1 MSB2 strain. These observations indicate
      that Msb2 is partially redundant with the Sho1 osmosensing branch for the
      activation of Ste11.

PMID- 12052882
TI  - Internalization-dependent and -independent requirements for transforming growth
      factor beta receptor signaling via the Smad pathway.
AB  - Members of the transforming growth factor beta (TGF-beta) family of proteins
      signal through cell surface transmembrane serine/threonine protein kinases known
      as type I and type II receptors. The TGF-beta signal is extended through
      phosphorylation of receptor-associated Smad proteins by the type I receptor.
      Although numerous investigations have established the sequence of events in TGF
      beta receptor (TGF-beta R) activation, none have examined the role of the
      endocytic pathway in initiation and/or maintenance of the signaling response. In
      this study we investigated whether TGF-beta R internalization modulates type I
      receptor activation, the formation of a functional receptor/Smad/SARA complex,
      Smad2/3 phosphorylation or nuclear translocation, and TGF-beta-dependent reporter
      gene activity. Our data provide evidence that, whereas type I receptor
      phosphorylation and association of SARA and Smad2 with the TGF-beta R complex
      take place independently of clathrin lattice formation, Smad2 or Smad3 activation
      and downstream signaling only occur after endocytic vesicle formation. Thus, TGF
      beta R endocytosis is not simply a way to dampen the signaling response but
      instead is required to propagate signaling via the Smad pathway.

PMID- 12052880
TI  - Proteomics of the eukaryotic transcription machinery: identification of proteins
      associated with components of yeast TFIID by multidimensional mass spectrometry.
AB  - The general transcription factor TFIID is a multisubunit complex of TATA-binding
      protein (TBP) and 14 distinct TBP-associated factors (TAFs). Although TFIID
      constituents are required for transcription initiation of most mRNA encoding
      genes, the mechanism of TFIID action remains unclear. To gain insight into TFIID
      function, we sought to generate a proteomic catalogue of proteins specifically
      interacting with TFIID subunits. Toward this end, TFIID was systematically
      immunopurified by using polyclonal antibodies directed against each subunit, and
      the constellation of TBP- and TAF-associated proteins was directly identified by
      coupled multidimensional liquid chromatography and tandem mass spectrometry. A
      number of novel protein-protein associations were observed, and several were
      characterized in detail. These interactions include association between TBP and
      the RSC chromatin remodeling complex, the TAF17p-dependent association of the
      Swi6p transactivator protein with TFIID, and the identification of three novel
      subunits of the SAGA acetyltransferase complex, including a putative ubiquitin
      specific protease component. Our results provide important new insights into the
      mechanisms of mRNA gene transcription and demonstrate the feasibility of
      constructing a complete proteomic interaction map of the eukaryotic transcription
      apparatus.

PMID- 12052883
TI  - The cell adhesion molecule M-cadherin is not essential for muscle development and
      regeneration.
AB  - M-cadherin is a classical calcium-dependent cell adhesion molecule that is highly
      expressed in developing skeletal muscle, satellite cells, and cerebellum. Based
      on its expression pattern and observations in cell culture, it has been
      postulated that M-cadherin may be important for the fusion of myoblasts to form
      myotubes, the correct localization and function of satellite cells during muscle
      regeneration, and the specialized architecture of adhering junctions in granule
      cells of cerebellar glomeruli. In order to investigate the potential roles of M
      cadherin in vivo, we generated a null mutation in mice. Mutant mice were viable
      and fertile and showed no gross developmental defects. In particular, the
      skeletal musculature appeared essentially normal. Moreover, muscle lesions
      induced by necrosis were efficiently repaired in mutant mice, suggesting that
      satellite cells are present, can be activated, and are able to form new
      myofibers. This was also confirmed by normal growth and fusion potential of
      mutant satellite cells cultured in vitro. In the cerebellum of M-cadherin-lacking
      mutants, typical contactus adherens junctions were present and similar in size
      and numbers to the equivalent junctions in wild-type animals. However, the
      adhesion plaques in the cerebellum of these mutants appeared to contain elevated
      levels of N-cadherin compared to wild-type animals. Taken together, these
      observations suggest that M-cadherin in the mouse serves no absolutely required
      function during muscle development and regeneration and is not essential for the
      formation of specialized cell contacts in the cerebellum. It seems that N
      cadherin or other cadherins can largely compensate for the lack of M-cadherin.

PMID- 12052884
TI  - Blimp-1-dependent repression of Pax-5 is required for differentiation of B cells
      to immunoglobulin M-secreting plasma cells.
AB  - B-cell lineage-specific activator protein (BSAP), encoded by the Pax-5 gene, is
      critical for B-cell lineage commitment and B-cell development but is not
      expressed in terminally differentiated B cells. We demonstrate a direct
      connection between BSAP and B-lymphocyte-induced maturation protein 1 (Blimp-1),
      a transcriptional repressor that is sufficient to drive plasmacytic
      differentiation. Blimp-1 binds a site on the Pax-5 promoter in vitro and in vivo
      and represses the Pax-5 promoter in a binding-site-dependent manner. By
      ectopically expressing Blimp-1 or a competitive inhibitor of Blimp-1, we show
      that Blimp-1 is both necessary and sufficient to repress Pax-5 during plasmacytic
      differentiation of primary splenic B cells. Blimp-1-dependent repression of Pax-5
      is sufficient to regulate BSAP targets CD19 and J chain and is necessary but not
      sufficient to induce XBP-1. We further show that repression of Pax-5 is required
      for Blimp-1 to drive differentiation of splenocytes to immunoglobulin M-secreting
      cells. Thus, repression of Pax-5 plays a critical role in the Blimp-1-dependent
      program of plasmacytic differentiation.

PMID- 12052885
TI  - Kinetics of a gamma interferon response: expression and assembly of CIITA
      promoter IV and inhibition by methylation.
AB  - Chromatin immunoprecipitation assays were employed to assess the kinetics of
      transcription factor assembly and histone modifications that occur during gamma
      interferon (IFN-gamma) induction of CIITA gene expression. CIITA is the master
      regulator of major histocompatibility complex class II transcription. Promoter IV
      (PIV), the major IFN-gamma responsive promoter for CIITA expression, requires
      both STAT1 and IFN regulatory factor 1 (IRF-1) for induction by IFN-gamma. STAT1
      binding to PIV was detected first and was accompanied by a modest acetylation of
      histones H3 and H4 that were associated with the region. Despite these changes,
      which occurred within 30 min of IFN-gamma treatment, CIITA mRNA was not detected
      until IRF-1 protein was synthesized and bound to its site, a process that
      required >120 min. In contrast to these events, fetal trophoblast-like cell
      lines, which are refractory to CIITA induction by IFN-gamma, failed to assemble
      the above factors or modify their chromatin, suggesting that accessibility to the
      promoter is blocked. Bisulfite sequencing of PIV showed strong hypermethylation
      of PIV, providing a link between methylation, chromatin structure, and factor
      binding. Together, this analysis provides a kinetic view of the activation of the
      CIITA gene in response to IFN-gamma and shows that regulatory factor assembly,
      chromatin modification, and gene expression proceed in discrete steps.

PMID- 12052886
TI  - A physical interaction between Gar1p and Rnt1pi is required for the nuclear
      import of H/ACA small nucleolar RNA-associated proteins.
AB  - During rRNA biogenesis, multiple RNA and protein substrates are modified and
      assembled through the coordinated activity of many factors. In Saccharomyces
      cerevisiae, the double-stranded RNA nuclease Rnt1p and the H/ACA snoRNA
      pseudouridylase complex participate in the transformation of the nascent pre-rRNA
      transcript into 35S pre-rRNA. Here we demonstrate the binding of a component of
      the H/ACA complex (Gar1p) to Rnt1p in vivo and in vitro in the absence of other
      factors. In vitro, Rnt1p binding to Gar1p is mutually exclusive of its RNA
      binding and cleavage activities. Mutations in Rnt1p that disrupt Gar1p binding do
      not inhibit RNA cleavage in vitro but slow RNA processing, prevent nucleolar
      localization of H/ACA snoRNA-associated proteins, and reduce pre-rRNA
      pseudouridylation in vivo. These results demonstrate colocalization of various
      components of the rRNA maturation complex and suggest a mechanism that links rRNA
      pseudouridylation and cleavage factors.

PMID- 12052887
TI  - Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth.
AB  - Blood vessel recruitment is an important feature of normal tissue growth. Here,
      we examined the role of Akt signaling in coordinating angiogenesis with skeletal
      muscle hypertrophy. Hypertrophy of C2C12 myotubes in response to insulin-like
      growth factor 1 or insulin and dexamethasone resulted in a marked increase in the
      secretion of vascular endothelial growth factor (VEGF). Myofiber hypertrophy and
      hypertrophy-associated VEGF synthesis were specifically inhibited by the
      transduction of a dominant-negative mutant of the Akt1 serine-threonine protein
      kinase. Conversely, transduction of constitutively active Akt1 increased myofiber
      size and led to a robust induction of VEGF protein production. Akt-mediated
      control of VEGF expression occurred at the level of transcription, and the
      hypoxia-inducible factor 1 regulatory element was dispensable for this
      regulation. The activation of Akt1 signaling in normal mouse gastrocnemius muscle
      was sufficient to promote myofiber hypertrophy, which was accompanied by an
      increase in circulating and tissue-resident VEGF levels and high capillary vessel
      densities at focal regions of high Akt transgene expression. In a rabbit hind
      limb model of vascular insufficiency, intramuscular activation of Akt1 signaling
      promoted collateral and capillary vessel formation and an accompanying increase
      in limb perfusion. These data suggest that myogenic Akt signaling controls both
      fiber hypertrophy and angiogenic growth factor synthesis, illustrating a
      mechanism through which blood vessel recruitment can be coupled to normal tissue
      growth.

PMID- 12052888
TI  - JDP2, a repressor of AP-1, recruits a histone deacetylase 3 complex to inhibit
      the retinoic acid-induced differentiation of F9 cells.
AB  - Up-regulation of the c-jun gene is a critical event in the retinoic acid (RA)
      mediated differentiation of embryonal carcinoma F9 cells. Activating
      transcription factor 2 (ATF-2) and p300 cooperate in the activation of
      transcription of the c-jun gene during the differentiation of F9 cells. We show
      here that the overexpression of Jun dimerization protein 2 (JDP2), a repressor of
      AP-1, inhibits the transactivation of the c-jun gene by ATF-2 and p300 by
      recruitment of the histone deacetylase 3 (HDAC3) complex, thereby repressing the
      RA-induced transcription of the c-jun gene and inhibiting the RA-mediated
      differentiation of F9 cells. Moreover, chromatin immunoprecipitation assays
      showed that the JDP2/HDAC3 complex, which binds to the differentiation response
      element within the c-jun promoter in undifferentiated F9 cells, was replaced by
      the p300 complex in response to RA, with an accompanying change in the histone
      acetylation status of the chromatin, the initiation of transcription of the c-jun
      gene, and the subsequent differentiation of F9 cells. These results suggest that
      JDP2 may be a key factor that controls the commitment of F9 cells to
      differentiation and shed new light on the mechanism by which an AP-1 repressor
      functions.

PMID- 12052889
TI  - Distinct cellular functions of MK2.
AB  - Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) is
      activated upon stress by p38 MAPK alpha and -beta, which bind to a basic docking
      motif in the C terminus of MK2 and which subsequently phosphorylate its
      regulatory sites. As a result of activation MK2 is exported from the nucleus to
      the cytoplasm and cotransports active p38 MAPK to this compartment. Here we show
      that the amount of p38 MAPK is significantly reduced in cells and tissues lacking
      MK2, indicating a stabilizing effect of MK2 for p38. Using a murine knockout
      model, we have previously shown that elimination of MK2 leads to a dramatic
      reduction of tumor necrosis factor (TNF) production in response to
      lipopolysaccharide. To further elucidate the role of MK2 in p38 MAPK
      stabilization and in TNF biosynthesis, we analyzed the ability of two MK2
      isoforms and several MK2 mutants to restore both p38 MAPK protein levels and TNF
      biosynthesis in macrophages. We show that MK2 stabilizes p38 MAPK through its C
      terminus and that MK2 catalytic activity does not contribute to this
      stabilization. Importantly, we demonstrate that stabilizing p38 MAPK does not
      restore TNF biosynthesis. TNF biosynthesis is only restored with MK2 catalytic
      activity. We further show that, in MK2-deficient macrophages, formation of
      filopodia in response to extracellular stimuli is reduced. In addition, migration
      of MK2-deficient mouse embryonic fibroblasts (MEFs) and smooth muscle cells on
      fibronectin is dramatically reduced. Interestingly, reintroducing catalytic MK2
      activity into MEFs alone is not sufficient to revert the migratory phenotype of
      these cells. In addition to catalytic activity, the proline-rich N-terminal
      region is necessary for rescuing the migratory phenotype. These data indicate
      that catalytic activity of MK2 is required for both cytokine production and cell
      migration. However, the proline-rich MK2 N terminus provides a distinct role
      restricted to cell migration.

PMID- 12052890
TI  - Chromosome instability as a result of double-strand breaks near telomeres in
      mouse embryonic stem cells.
AB  - Telomeres are essential for protecting the ends of chromosomes and preventing
      chromosome fusion. Telomere loss has been proposed to play an important role in
      the chromosomal rearrangements associated with tumorigenesis. To determine the
      relationship between telomere loss and chromosome instability in mammalian cells,
      we investigated the events resulting from the introduction of a double-strand
      break near a telomere with I-SceI endonuclease in mouse embryonic stem cells. The
      inactivation of a selectable marker gene adjacent to a telomere as a result of
      the I-SceI-induced double-strand break involved either the addition of a telomere
      at the site of the break or the formation of inverted repeats and large tandem
      duplications on the end of the chromosome. Nucleotide sequence analysis
      demonstrated large deletions and little or no complementarity at the
      recombination sites involved in the formation of the inverted repeats. The
      formation of inverted repeats was followed by a period of chromosome instability,
      characterized by amplification of the subtelomeric region, translocation of
      chromosomal fragments onto the end of the chromosome, and the formation of
      dicentric chromosomes. Despite this heterogeneity, the rearranged chromosomes
      eventually acquired telomeres and were stable in most of the cells in the
      population at the time of analysis. Our observations are consistent with a model
      in which broken chromosomes that do not regain a telomere undergo sister
      chromatid fusion involving nonhomologous end joining. Sister chromatid fusion is
      followed by chromosome instability resulting from breakage-fusion-bridge cycles
      involving the sister chromatids and rearrangements with other chromosomes. This
      process results in highly rearranged chromosomes that eventually become stable
      through the addition of a telomere onto the broken end. We have observed similar
      events after spontaneous telomere loss in a human tumor cell line, suggesting
      that chromosome instability resulting from telomere loss plays a role in
      chromosomal rearrangements associated with tumor cell progression.

PMID- 12052891
TI  - Caspase processing and nuclear export of CTP:phosphocholine cytidylyltransferase
      alpha during farnesol-induced apoptosis.
AB  - CTP:phosphocholine cytidylyltransferase alpha (CCT alpha) is a nuclear enzyme
      that catalyzes the rate-limiting step in the CDP-choline pathway, the primary
      route for synthesis of phosphatidylcholine (PtdCho) in eukaryotic cells.
      Induction of apoptosis by farnesol (FOH) and other cytotoxic drugs has been shown
      to alter PtdCho synthesis via the CDP-choline pathway. Here we report that FOH
      induced apoptosis in CHO cells caused a dose-dependent activation of CCT alpha
      and inhibition of the final step in the pathway, resulting in a biphasic effect
      on PtdCho synthesis. Activation of CCT alpha was accompanied by enzyme
      translocation to the nuclear envelope within 30 min of FOH addition to cells.
      Following translocation to membranes, CCT alpha was exported from the nucleus and
      underwent caspase-mediated proteolysis that coincided with poly(ADP-ribose)
      polymerase cleavage. Site-directed mutagenesis and in vivo and in vitro
      expression studies mapped a caspase 6 and/or 8 cleavage site to TEED(28 downward
      arrow)G, the final residue in the CCT alpha nuclear localization signal. Nuclear
      export of CCT alpha appeared to be an active process in FOH-treated CHO cells
      that was independent of caspase removal of the nuclear localization signal.
      Caspase cleavage of CCT alpha occurred during UV or chelerythrine-induced
      apoptosis; however, nuclear membrane translocation and nuclear export were not
      evident under these conditions. Thus, caspase cleavage of CCT alpha was a late
      feature of several apoptotic programs that occurred in the nucleus or at the
      nuclear envelope. Activation and nuclear export of CCT alpha were early events in
      FOH-induced apoptosis that contributed to altered PtdCho synthesis and, in
      conjunction with caspase cleavage, excluded CCT alpha from the nucleus.

PMID- 12052893
TI  - Replication and subnuclear location dynamics of the immunoglobulin heavy-chain
      locus in B-lineage cells.
AB  - The murine immunoglobulin heavy-chain (Igh) locus provides an important model for
      understanding the replication of tissue-specific gene loci in mammalian cells. We
      have observed two DNA replication programs with dramatically different temporal
      replication patterns for the Igh locus in B-lineage cells. In pro- and pre-B-cell
      lines and in ex vivo-expanded pro-B cells, the entire locus is replicated early
      in S phase. In three cell lines that exhibit the early-replication pattern, we
      found that replication forks progress in both directions through the constant
      region genes, which is consistent with the activation of multiple initiation
      sites. In contrast, in plasma cell lines, replication of the Igh locus occurs
      through a triphasic pattern similar to that previously detected in MEL cells.
      Sequences downstream of the Igh-C alpha gene replicate early in S, while heavy
      chain variable (Vh) gene sequences replicate late in S. An approximately 500-kb
      transition region connecting sequences that replicate early and late is
      replicated progressively later in S. The formation of the transition region in
      different cell lines is independent of the sequences encompassed. In B-cell lines
      that exhibit a triphasic-replication pattern, replication forks progress in one
      direction through the examined constant-region genes. Timing data and the
      direction of replication fork movement indicate that replication of the
      transition region occurs by a single replication fork, as previously described
      for MEL cells. Associated with the contrasting replication programs are
      differences in the subnuclear locations of Igh loci. When the entire locus is
      replicated early in S, the Igh locus is located away from the nuclear periphery,
      but when Vh gene sequences replicate late and there is a temporal-transition
      region, the entire Igh locus is located near the nuclear periphery.

PMID- 12052892
TI  - Cyclin D and cdk4 are required for normal development beyond the blastula stage
      in sea urchin embryos.
AB  - cdk4 mRNA and protein are constitutively expressed in sea urchin eggs and
      throughout embryonic development. In contrast, cyclin D mRNA is barely detectable
      in eggs and early embryos, when the cell cycles consist of alternating S and M
      phases. Cyclin D mRNA increases dramatically in embryos at the early blastula
      stage and remains at a constant level throughout embryogenesis. An increase in
      cdk4 kinase activity occurs concomitantly with the increase in cyclin D mRNA.
      Ectopic expression of cyclin D mRNA in eggs arrests development before the 16
      cell stage and causes eventual embryonic death, suggesting that activation of
      cyclin D/cdk4 in cleavage cell cycles is lethal to the embryo. In contrast,
      blocking cyclin D or cdk4 expression with morpholino antisense oligonucleotides
      results in normal development of early gastrula-stage embryos but abnormal,
      asymmetric larvae. These results suggest that in sea urchins, cyclin D and cdk4
      are required for normal development and perhaps the patterning of the developing
      embryo, but may not be directly involved in regulating entry into the cell cycle.

PMID- 12052894
TI  - The human candidate tumor suppressor gene HIC1 recruits CtBP through a degenerate
      GLDLSKK motif.
AB  - HIC1 (hypermethylated in cancer) and its close relative HRG22 (HIC1-related gene
      on chromosome 22) encode transcriptional repressors with five C(2)H(2) zinc
      fingers and an N-terminal BTB/POZ autonomous transcriptional repression domain
      that is unable to recruit histone deacetylases (HDACs). Alignment of the HIC1 and
      HRG22 proteins from various species highlighted a perfectly conserved GLDLSKK/R
      motif highly related to the consensus CtBP interaction motif (PXDLSXK/R), except
      for the replacement of the virtually invariant proline by a glycine. HIC1
      strongly interacts with mCtBP1 both in vivo and in vitro through this conserved
      GLDLSKK motif, thus extending the CtBP consensus binding site. The BTB/POZ domain
      does not interact with mCtBP1, but the dimerization of HIC1 through this domain
      is required for the interaction with mCtBP1. When tethered to DNA by fusion with
      the Gal4 DNA-binding domain, the HIC1 central region represses transcription
      through interactions with CtBP in a trichostatin A-sensitive manner. In
      conclusion, our results demonstrate that HIC1 mediates transcriptional repression
      by both HDAC-independent and HDAC-dependent mechanisms and show that CtBP is a
      HIC1 corepressor that is recruited via a variant binding site.

PMID- 12052895
TI  - Rad23 promotes the targeting of proteolytic substrates to the proteasome.
AB  - Rad23 contains a ubiquitin-like domain (UbL(R23)) that interacts with
      catalytically active proteasomes and two ubiquitin (Ub)-associated (UBA)
      sequences that bind Ub. The UBA domains can bind Ub in vitro, although the
      significance of this interaction in vivo is poorly understood. Rad23 can
      interfere with the assembly of multi-Ub chains in vitro, and high-level
      expression caused stabilization of proteolytic substrates in vivo. We report here
      that Rad23 interacts with ubiquitinated cellular proteins through the synergistic
      action of its UBA domains. Rad23 plays an overlapping role with Rpn10, a
      proteasome-associated multi-Ub chain binding protein. Mutations in the UBA
      domains prevent efficient interaction with ubiquitinated proteins and result in
      poor suppression of the growth and proteolytic defects of a rad23 Delta rpn10
      Delta mutant. High-level expression of Rad23 revealed, for the first time, an
      interaction between ubiquitinated proteins and the proteasome. This increase was
      not observed in rpn10 Delta mutants, suggesting that Rpn10 participates in the
      recognition of proteolytic substrates that are delivered by Rad23. Overexpression
      of UbL(R23) caused stabilization of a model substrate, indicating that an
      unregulated UbL(R23)-proteasome interaction can interfere with the efficient
      delivery of proteolytic substrates by Rad23. Because the suppression of a rad23
      Delta rpn10 Delta mutant phenotype required both UbL(R23) and UBA domains, our
      findings support the hypothesis that Rad23 encodes a novel regulatory factor that
      translocates ubiquitinated substrates to the proteasome.

PMID- 12052896
TI  - Yeast Ysl2p, homologous to Sec7 domain guanine nucleotide exchange factors,
      functions in endocytosis and maintenance of vacuole integrity and interacts with
      the Arf-Like small GTPase Arl1p.
AB  - We previously described the isolation of ysl2-1 due to its genetic interaction
      with Delta ypt51/vps21, a mutant with a deletion of the coding sequence for the
      yeast Rab5 homolog, which regulates endocytic traffic between early and late
      endosomes. Here we report that Ysl2p is a novel 186.8-kDa peripheral membrane
      protein homologous to members of the Sec7 family. We provide multiple genetic and
      biochemical evidence for an interaction between Ysl12p and the Arf-like protein
      Arl1p, consistent with a potential function as an Arf guanine nucleotide exchange
      factor (GEF). The temperature-sensitive alleles ysl2-307 and ysl2-316 are
      specifically defective in ligand-induced degradation of Ste2p and alpha-factor
      and exhibit vacuole fragmentation directly upon a shift to 37 degrees C. In
      living cells, green fluorescent protein (GFP)-Ysl2p colocalizes with endocytic
      elements that accumulate FM4-64. The GFP-Ysl2p staining is sensitive to a
      mutation in VPS27 resulting in the formation of an aberrant class E compartment,
      but it is not affected by a sec7 mutation. Consistent with the idea that Ysl2p
      and Arl1p have closely related functions, Delta arl1 cells are defective in
      endocytic transport and in vacuolar protein sorting.

PMID- 12052897
TI  - The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal
      transduction by c-Jun NH(2)-terminal kinase.
AB  - Targeted gene disruption studies have established that the c-Jun NH(2)-terminal
      kinase (JNK) signaling pathway is required for stress-induced release of
      mitochondrial cytochrome c and apoptosis. Here we demonstrate that activated JNK
      is sufficient to induce rapid cytochrome c release and apoptosis. However,
      activated JNK fails to cause death in cells deficient of members of the Bax
      subfamily of proapoptotic Bcl2-related proteins. Furthermore, exposure to stress
      fails to activate Bax, cause cytochrome c release, and induce death in JNK
      deficient cells. These data demonstrate that proapoptotic members of the Bax
      protein subfamily are essential for JNK-dependent apoptosis.

PMID- 12052899
TI  - Promoter specificity and biological activity of tethered AP-1 dimers.
AB  - Activator protein 1 (AP-1) is a group of dimeric transcription factors composed
      of Jun, Fos, and ATF family proteins. Both gain- and loss-of-function studies
      have revealed specific roles for individual AP-1 components in cell
      proliferation, differentiation, apoptosis, and other biological processes.
      However, little is known about the functions of specific AP-1 dimers. To test the
      importance of AP-1 composition in transcriptional activation, AP-1 monomers were
      joined via a flexible polypeptide tether to force specific pairing. The resultant
      single-chain AP-1 molecules showed DNA binding specificity and transcriptional
      activation potentials similar to those of untethered dimers, even in the presence
      of dominant-negative AP-1 monomers. c-Jun-containing dimers showed distinct
      promoter specificity in transient-transfection experiments, depending on the Fos,
      Fra, or ATF partner. When stably expressed in NIH 3T3 cells, c-Jun tethered dimer
      Fra2, but not c-Jun tethered dimer Fra1 and c-Jun tethered dimer cFos (the tilde
      indicates a tethered dimer), inhibited G(0) arrest at confluency and under low
      serum conditions and specifically activated cyclin A expression. These data
      suggest that the choice of dimerization partner defines the role of c-Jun in gene
      activation and cell cycle regulation and that single-chain AP-1 molecules provide
      a powerful tool for assessing the role of specific AP-1 dimers.

PMID- 12052898
TI  - Maleylacetoacetate isomerase (MAAI/GSTZ)-deficient mice reveal a glutathione
      dependent nonenzymatic bypass in tyrosine catabolism.
AB  - In mammals, the catabolic pathway of phenylalanine and tyrosine is found in liver
      (hepatocytes) and kidney (proximal tubular cells). There are well-described human
      diseases associated with deficiencies of all enzymes in this pathway except for
      maleylacetoacetate isomerase (MAAI), which converts maleylacetoacetate (MAA) to
      fumarylacetoacetate (FAA). MAAI is also known as glutathione transferase zeta
      (GSTZ1). Here, we describe the phenotype of mice with a targeted deletion of the
      MAAI (GSTZ1) gene. MAAI-deficient mice accumulated FAA and succinylacetone in
      urine but appeared otherwise healthy. This observation suggested that either
      accumulating MAA is not toxic or an alternate pathway for MAA metabolism exists.
      A complete redundancy of MAAI could be ruled out because substrate overload of
      the tyrosine catabolic pathway (administration of homogentisic acid,
      phenylalanine, or tyrosine) resulted in renal and hepatic damage. However,
      evidence for a partial bypass of MAAI activity was also found. Mice doubly mutant
      for MAAI and fumarylacetoacetate hydrolase (FAH) died rapidly on a normal diet,
      indicating that MAA could be isomerized to FAA in the absence of MAAI. Double
      mutants showed predominant renal injury, indicating that this organ is the
      primary target for the accumulated compound(s) resulting from MAAI deficiency. A
      glutathione-mediated isomerization of MAA to FAA independent of MAAI enzyme was
      demonstrated in vitro. This nonenzymatic bypass is likely responsible for the
      lack of a phenotype in nonstressed MAAI mutant mice.

PMID- 12052900
TI  - Covariation of synaptonemal complex length and mammalian meiotic exchange rates.
AB  - Analysis of recombination between loci (linkage analysis) has been a cornerstone
      of human genetic research, enabling investigators to localize and, ultimately,
      identify genetic loci. However, despite these efforts little is known about
      patterns of meiotic exchange in human germ cells or the mechanisms that control
      these patterns. Using recently developed immunofluorescence methodology to
      examine exchanges in human spermatocytes, we have identified remarkable variation
      in the rate of recombination within and among individuals. Subsequent analyses
      indicate that, in humans and mice, this variation is linked to differences in the
      length of the synaptonemal complex. Thus, at least in mammals, a physical
      structure, the synaptonemal complex, reflects genetic rather than physical
      distance.

PMID- 12052901
TI  - Role of formins in actin assembly: nucleation and barbed-end association.
AB  - Nucleation of branched actin filaments by the Arp2/3 complex is a conserved
      process in eukaryotic cells, yet the source of unbranched actin filaments has
      remained obscure. In yeast, formins stimulate assembly of actin cables
      independently of Arp2/3. Here, the conserved core of formin homology domains 1
      and 2 of Bni1p (Bni1pFH1FH2) was found to nucleate unbranched actin filaments in
      vitro. Bni1pFH2 provided the minimal region sufficient for nucleation. Unique
      among actin nucleators, Bni1pFH1FH2 remained associated with the growing barbed
      ends of filaments. This combination of properties suggests a direct role for
      formins in regulating nucleation and polarization of unbranched filamentous actin
      structures.

PMID- 12052902
TI  - Surface melt-induced acceleration of Greenland ice-sheet flow.
AB  - Ice flow at a location in the equilibrium zone of the west-central Greenland Ice
      Sheet accelerates above the midwinter average rate during periods of summer
      melting. The near coincidence of the ice acceleration with the duration of
      surface melting, followed by deceleration after the melting ceases, indicates
      that glacial sliding is enhanced by rapid migration of surface meltwater to the
      ice-bedrock interface. Interannual variations in the ice acceleration are
      correlated with variations in the intensity of the surface melting, with larger
      increases accompanying higher amounts of summer melting. The indicated coupling
      between surface melting and ice-sheet flow provides a mechanism for rapid, large
      scale, dynamic responses of ice sheets to climate warming.

PMID- 12052903
TI  - The human genome project and its impact on psychiatry.
AB  - There has been substantial evidence for more than three decades that the major
      psychiatric illnesses such as schizophrenia, bipolar disorder, autism, and
      alcoholism have a strong genetic basis. During the past 15 years considerable
      effort has been expended in trying to establish the genetic loci associated with
      susceptibility to these and other mental disorders using principally linkage
      analysis. Despite this, only a handful of specific genes have been identified,
      and it is now generally recognized that further advances along these lines will
      require the analysis of literally hundreds of affected individuals and their
      families. Fortunately, the emergence in the past three years of a number of new
      approaches and more effective tools has given new hope to those engaged in the
      search for the underlying genetic and environmental factors involved in causing
      these illnesses, which collectively are among the most serious in all societies.
      Chief among these new tools is the availability of the entire human genome
      sequence and the prospect that within the next several years the entire
      complement of human genes will be known and the functions of most of their
      protein products elucidated. In the meantime the search for susceptibility loci
      is being facilitated by the availability of single nucleotide polymorphisms
      (SNPs) and by the beginning of haplotype mapping, which tracks the distribution
      of clusters of SNPs that segregate as a group. Together with high throughput DNA
      sequencing, microarrays for whole genome scanning, advances in proteomics, and
      the development of more sophisticated computer programs for analyzing sequence
      and association data, these advances hold promise of greatly accelerating the
      search for the genetic basis of most mental illnesses while, at the same time,
      providing molecular targets for the development of new and more effective
      therapies.

PMID- 12052904
TI  - Auditory system development: primary auditory neurons and their targets.
AB  - The neurons of the cochlear ganglion transmit acoustic information between the
      inner ear and the brain. These placodally derived neurons must produce a
      topographically precise pattern of connections in both the inner ear and the
      brain. In this review, we consider the current state of knowledge concerning the
      development of these neurons, their peripheral and central connections, and their
      influences on peripheral and central target cells. Relatively little is known
      about the cellular and molecular regulation of migration or the establishment of
      precise topographic connection to the hair cells or cochlear nucleus (CN)
      neurons. Studies of mice with neurotrophin deletions are beginning to yield
      increasing understanding of variations in ganglion cell survival and resulting
      innervation patterns, however. Finally, existing evidence suggests that while
      ganglion cells have little influence on the differentiation of their hair cell
      targets, quite the opposite is true in the brain. Ganglion cell innervation and
      synaptic activity are essential for normal development of neurons in the cochlear
      nucleus.

PMID- 12052905
TI  - AMPA receptor trafficking and synaptic plasticity.
AB  - Activity-dependent changes in synaptic function are believed to underlie the
      formation of memories. Two prominent examples are long-term potentiation (LTP)
      and long-term depression (LTD), whose mechanisms have been the subject of
      considerable scrutiny over the past few decades. Here we review the growing
      literature that supports a critical role for AMPA receptor trafficking in LTP and
      LTD, focusing on the roles proposed for specific AMPA receptor subunits and their
      interacting proteins. While much work remains to understand the molecular basis
      for synaptic plasticity, recent results on AMPA receptor trafficking provide a
      clear conceptual framework for future studies.

PMID- 12052906
TI  - Molecular control of cortical dendrite development.
AB  - Dendritic morphology has a profound impact on neuronal information processing.
      The overall extent and orientation of dendrites determines the kinds of input a
      neuron receives. Fine dendritic appendages called spines act as subcellular
      compartments devoted to processing synaptic information, and the dendritic
      branching pattern determines the efficacy with which synaptic information is
      transmitted to the soma. The acquisition of a mature dendritic morphology depends
      on the coordinated action of a number of different extracellular factors. Here we
      discuss this evidence in the context of dendritic development in the cerebral
      cortex. Soon after migrating to the cortical plate, neurons extend an apical
      dendrite directed toward the pial surface. The oriented growth of the apical
      dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant.
      Subsequent dendritic development involves signaling by neurotrophic factors and
      Notch, which regulate dendritic growth and branching. During postnatal
      development the formation and stabilization of dendritic spines are regulated in
      part by patterns of synaptic activity. These observations suggest that
      extracellular signals play an important role in regulating every aspect of
      dendritic development and thereby exert a critical influence on cortical
      connectivity.

PMID- 12052907
TI  - Functional MRI of language: new approaches to understanding the cortical
      organization of semantic processing.
AB  - Until recently, our understanding of how language is organized in the brain
      depended on analysis of behavioral deficits in patients with fortuitously placed
      lesions. The availability of functional magnetic resonance imaging (fMRI) for in
      vivo analysis of the normal brain has revolutionized the study of language. This
      review discusses three lines of fMRI research into how the semantic system is
      organized in the adult brain. These are (a) the role of the left inferior frontal
      lobe in semantic processing and dissociations from other frontal lobe language
      functions, (b) the organization of categories of objects and concepts in the
      temporal lobe, and (c) the role of the right hemisphere in comprehending
      contextual and figurative meaning. Together, these lines of research broaden our
      understanding of how the brain stores, retrieves, and makes sense of semantic
      information, and they challenge some commonly held notions of functional
      modularity in the language system.

PMID- 12052908
TI  - Intentional maps in posterior parietal cortex.
AB  - The posterior parietal cortex (PPC), historically believed to be a sensory
      structure, is now viewed as an area important for sensory-motor integration.
      Among its functions is the forming of intentions, that is, high-level cognitive
      plans for movement. There is a map of intentions within the PPC, with different
      subregions dedicated to the planning of eye movements, reaching movements, and
      grasping movements. These areas appear to be specialized for the multisensory
      integration and coordinate transformations required to convert sensory input to
      motor output. In several subregions of the PPC, these operations are facilitated
      by the use of a common distributed space representation that is independent of
      both sensory input and motor output. Attention and learning effects are also
      evident in the PPC. However, these effects may be general to cortex and operate
      in the PPC in the context of sensory-motor transformations.

PMID- 12052909
TI  - Beyond phrenology: what can neuroimaging tell us about distributed circuitry?
AB  - Unsupervised models of how the brain identifies and categorizes the causes of its
      sensory input can be divided into two classes: those that minimize the mutual
      information (i.e., redundancy) among evoked responses and those that minimize the
      prediction error. Although these models have the same goal, the way that goal is
      attained, and the functional architectures required, are fundamentally different.
      This review describes the differences, in the functional anatomy of sensory
      cortical hierarchies, implied by the two models. We then consider how
      neuroimaging can be used to disambiguate between them. The key distinction
      reduces to whether backward connections are employed by the brain to generate a
      prediction of sensory inputs. To ascertain whether backward influences are
      evident empirically requires a characterization of functional integration among
      brain systems. This review summarizes the approaches to measuring functional
      integration in terms of effective connectivity and proceeds to address the
      question posed by the theoretical considerations. In short, it will be shown that
      the conjoint manipulation of bottom-up and top-down inputs to an area can be used
      to test for interactions between them, in elaborating cortical responses. The
      conclusion, from these sorts of neuroimaging studies, points to the prevalence of
      top-down influences and the plausibility of generative models of sensory brain
      function.

PMID- 12052910
TI  - Transcriptional codes and the control of neuronal identity.
AB  - The topographic assembly of neural circuits is dependent upon the generation of
      specific neuronal subtypes, each subtype displaying unique properties that direct
      the formation of selective connections with appropriate target cells. Studies of
      motor neuron development in the spinal cord have begun to elucidate the molecular
      mechanisms involved in controlling motor projections. In this review, we first
      describe the actions of transcription factors within motor neuron progenitors,
      which initiate a cascade of transcriptional interactions that lead to motor
      neuron specification. We next highlight the contribution of the LIM homeodomain
      (LIM-HD) transcription factors in establishing motor neuron subtype identity.
      Importantly, it has recently been shown that the combinatorial expression of LIM
      HD transcription factors, the LIM code, confers motor neuron subtypes with the
      ability to select specific axon pathways to reach their distinct muscle targets.
      Finally, the downstream targets of the LIM code are discussed, especially in the
      context of subtype-specific motor axon pathfinding.

PMID- 12052911
TI  - The role of hypocretins (orexins) in sleep regulation and narcolepsy.
AB  - The hypocretins (orexins) are two novel neuropeptides (Hcrt-1 and Hcrt-2),
      derived from the same precursor gene, that are synthesized by neurons located
      exclusively in the lateral, posterior, and perifornical hypothalamus. Hypocretin
      containing neurons have widespread projections throughout the CNS with
      particularly dense excitatory projections to monoaminergic centers such as the
      noradrenergic locus coeruleus, histaminergic tuberomammillary nucleus,
      serotoninergic raphe nucleus, and dopaminergic ventral tegmental area. The
      hypocretins were originally believed to be primarily important in the regulation
      of appetite; however, a major function emerging from research on these
      neuropeptides is the regulation of sleep and wakefulness. Deficiency in
      hypocretin neurotransmission results in the sleep disorder narcolepsy in mice,
      dogs, and humans. The hypocretins are also uniquely positioned to link sleep,
      appetite, and neuroendocrine control. The aim of this review is to describe and
      discuss the current knowledge regarding the hypocretin neurotransmitter system in
      narcolepsy and normal sleep.

PMID- 12052912
TI  - A decade of molecular studies of fragile X syndrome.
AB  - Fragile X syndrome is one of the most common forms of inherited mental
      retardation. In most cases the disease is caused by the methylation-induced
      transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene that
      occurs as a result of the expansion of a CGG repeat in the gene's 5'UTR and leads
      to the loss of protein product fragile X mental retardation protein (FMRP). FMRP
      is an RNA binding protein that associates with translating polyribosomes as part
      of a large messenger ribonucleoprotein (mRNP) and modulates the translation of
      its RNA ligands. Pathological studies from the brains of patients and from Fmr1
      knockout mice show abnormal dendritic spines implicating FMRP in synapse
      formation and function. Evidence from both in vitro and in vivo neuronal studies
      indicates that FMRP is located at the synapse and the loss of FMRP alters
      synaptic plasticity. As synaptic plasticity has been implicated in learning and
      memory, analysis of synapse abnormalities in patients and Fmr1 knockout mice
      should prove useful in studying the pathogenesis of fragile X syndrome and
      understanding learning and cognition in general. If an appreciable portion of the
      total variance (in IQ) is due to sex linked genes, it is of more importance that
      a boy should have a clever mother than a clever father. Hogben 1932 (quoted in
      Lehrke 1974)

PMID- 12052913
TI  - Contextual influences on visual processing.
AB  - The visual image formed on the retina represents an amalgam of visual scene
      properties, including the reflectances of surfaces, their relative positions, and
      the type of illumination. The challenge facing the visual system is to extract
      the "meaning" of the image by decomposing it into its environmental causes. For
      each local region of the image, that extraction of meaning is only possible if
      information from other regions is taken into account. Of particular importance is
      a set of image cues revealing surface occlusion and/or lighting conditions. These
      information-rich cues direct the perceptual interpretation of other more
      ambiguous image regions. This context-dependent transformation from image to
      perception has profound-but frequently under-appreciated-implications for
      neurophysiological studies of visual processing: To demonstrate that neuronal
      responses are correlated with perception of visual scene properties, rather than
      visual image features, neuronal sensitivity must be assessed in varied contexts
      that differentially influence perceptual interpretation. We review a number of
      recent studies that have used this context-based approach to explore the neuronal
      bases of visual scene perception.

PMID- 12052915
TI  - Schizophrenia as a disorder of neurodevelopment.
AB  - A combination of genetic susceptibility and environmental perturbations appear to
      be necessary for the expression of schizophrenia. In addition, the pathogenesis
      of the disease is hypothesized to be neurodevelopmental in nature based on
      reports of an excess of adverse events during the pre- and perinatal periods, the
      presence of cognitive and behavioral signs during childhood and adolescence, and
      the lack of evidence of a neurodegenerative process in most individuals with
      schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest
      that no single gene or factor is responsible for driving a highly complex
      biological process. Together, these findings suggest that combinatorial genetic
      and environmental factors, which disturb a normal developmental course early in
      life, result in molecular and histogenic responses that cumulatively lead to
      different developmental trajectories and the clinical phenotype recognized as
      schizophrenia.

PMID- 12052914
TI  - Large-scale sources of neural stem cells.
AB  - Large-scale sources of neural stem cells are crucial for both basic research and
      novel approaches toward treating neurological disorders. Three sources that
      produce neural cells closely resembling their normal counterparts are now
      available: oncogene immortalized stem cells, neurospheres, and embryonic stem
      cell (ES)-derived neural cells. Cells including multiple subtypes of CNS and PNS
      neurons, as well as oligodendrocytes, Schwann cells, and astrocytes, are modeled
      by these large-scale sources. Although most cell lines were originally from
      rodents, their human counterparts are being discovered and characterized.

PMID- 12052916
TI  - The central autonomic nervous system: conscious visceral perception and autonomic
      pattern generation.
AB  - The overall organization of the peripheral autonomic nervous system has been
      known for many decades, but the mechanisms by which it is controlled by the
      central nervous system are just now coming to light. In particular, two major
      issues have seen considerable progress in the past decade. First, the pathways
      that provide visceral sensation to conscious perception at a cortical level have
      been elucidated in both animals and humans. The nociceptive system runs in
      parallel to the pathways carrying visceral sensation from the cranial nerves and
      may be considered in itself a component of visceral sensation. Second, structures
      in the central nervous system that generate patterns of autonomic response have
      been identified. These pattern generators are located at multiple levels of the
      central nervous system, and they can be combined in temporal and spatial patterns
      to subserve a wide range of behavioral needs.

PMID- 12052917
TI  - The role of notch in promoting glial and neural stem cell fates.
AB  - The Notch signaling pathway has long been known to influence cell fate in the
      developing nervous system. However, this pathway has generally been thought to
      inhibit the specification of certain cell types in favor of others, or to simply
      maintain a progenitor pool. Recently, this view has been challenged by numerous
      studies suggesting that Notch may play an instructive role in promoting glial
      development. This work has inspired a new look at the role of Notch signaling in
      specifying cell fate. It has also prompted further consideration of the emerging
      view that in some contexts glia may be multipotent progenitors. This review
      examines the role of Notch during gliogenesis in both fruit flies and
      vertebrates, as well as evidence in vertebrates that some glia may be stem cells.

PMID- 12052918
TI  - Multiple sclerosis: deeper understanding of its pathogenesis reveals new targets
      for therapy.
AB  - Recent technological breakthroughs allowing for large-scale analysis of gene
      transcripts and large-scale monitoring of the immune response with protein chips
      are revealing new participants in the pathogenesis of multiple sclerosis. Some of
      these participants may be useful targets for therapy.

PMID- 12052919
TI  - Wired for reproduction: organization and development of sexually dimorphic
      circuits in the mammalian forebrain.
AB  - Mammalian reproduction depends on the coordinated expression of behavior with
      precisely timed physiological events that are fundamentally different in males
      and females. An improved understanding of the neuroanatomical relationships
      between sexually dimorphic parts of the forebrain has contributed to a
      significant paradigm shift in how functional neural systems are approached
      experimentally. This review focuses on the organization of interconnected limbic
      hypothalamic pathways that participate in the neural control of reproduction and
      summarizes what is known about the developmental neurobiology of these pathways.
      Sex steroid hormones such as estrogen and testosterone have much in common with
      neurotrophins and regulate cell death, neuronal migration, neurogenesis, and
      neurotransmitter plasticity. In addition, these hormones direct formation of
      sexually dimorphic circuits by influencing axonal guidance and synaptogenesis.
      The signaling events underlying the developmental activities of sex steroids
      involve interactions between nuclear hormone receptors and other transcriptional
      regulators, as well as interactions at multiple levels with neurotrophin and
      neurotransmitter signal transduction pathways.

PMID- 12052920
TI  - Central nervous system damage, monocytes and macrophages, and neurological
      disorders in AIDS.
AB  - This review focuses on the role of the extended macrophage/monocyte family in the
      central nervous system during HIV or SIV infection. The accumulated data,
      buttressed by recent experimental results, suggest that these cells play a
      central, pathogenic role in retroviral-associated CNS disease. While the immune
      system is able to combat the underlying retroviral infection, the accumulation
      and widespread activation of macrophages, microglia, and perivascular cells in
      the CNS are held in check. However, with the collapse of the immune system and
      the disappearance of the CD4(+) T cell population, productive infection
      reemerges, especially in CNS macrophages. These cells, as well as noninfected
      macrophages, are stimulated to high levels of activation. When members of this
      cell group become highly activated, they elaborate a wide spectrum of deleterious
      substances into the neural parenchyma. In the final phases of HIV or SIV
      infection, this chronic, widespread, and dramatic level of
      macrophage/monocyte/microglial activation constitutes a self-sustaining state of
      macrophage dysregulation, which results in pathological alterations and the
      emergence of various neurological problems.

PMID- 12052922
TI  - When science and politics don't mix.

PMID- 12052921
TI  - Learning and memory functions of the Basal Ganglia.
AB  - Although the mammalian basal ganglia have long been implicated in motor behavior,
      it is generally recognized that the behavioral functions of this subcortical
      group of structures are not exclusively motoric in nature. Extensive evidence now
      indicates a role for the basal ganglia, in particular the dorsal striatum, in
      learning and memory. One prominent hypothesis is that this brain region mediates
      a form of learning in which stimulus-response (S-R) associations or habits are
      incrementally acquired. Support for this hypothesis is provided by numerous
      neurobehavioral studies in different mammalian species, including rats, monkeys,
      and humans. In rats and monkeys, localized brain lesion and pharmacological
      approaches have been used to examine the role of the basal ganglia in S-R
      learning. In humans, study of patients with neurodegenerative diseases that
      compromise the basal ganglia, as well as research using brain neuroimaging
      techniques, also provide evidence of a role for the basal ganglia in habit
      learning. Several of these studies have dissociated the role of the basal ganglia
      in S-R learning from those of a cognitive or declarative medial temporal lobe
      memory system that includes the hippocampus as a primary component. Evidence
      suggests that during learning, basal ganglia and medial temporal lobe memory
      systems are activated simultaneously and that in some learning situations
      competitive interference exists between these two systems.

PMID- 12052923
TI  - Research ethics. Germany gets in step with scientific misconduct rules.

PMID- 12052924
TI  - Intellectual property. High court reins in patent pirates.

PMID- 12052925
TI  - Biomedical research. Australia pushes stem cell advantage.

PMID- 12052927
TI  - Particle physics. Dark-matter 'sighting' returns to shadows.

PMID- 12052926
TI  - Materials science. Lighting initiative flickers to life.
AB  - Researchers met in New Mexico last week to map out priorities for the proposed
      Next Generation Lighting Initiative embedded in a broader energy bill moving
      through Congress. The 10-year, $500 million project is designed to help the
      United States stay ahead of competitors in Japan, Europe, and Korea for global
      leadership in the $40 billion lighting industry.

PMID- 12052928
TI  - Infectious disease. Cholera strengthened by trip through gut.

PMID- 12052929
TI  - Organic chemistry. New-model reactions skip the drip.

PMID- 12052930
TI  - Ecology. Signs of stress seen in snowmobile season.

PMID- 12052931
TI  - Canada. Social scientists go for a political dip.

PMID- 12052932
TI  - Rice sequence data. Syngenta agrees to wider release.

PMID- 12052933
TI  - Global warming. Rain might be leading carbon sink factor.

PMID- 12052935
TI  - Space science. China teams with Europe on exploration of magnetosphere.

PMID- 12052934
TI  - Space science. Science emerges from shadows of China's space program.

PMID- 12052936
TI  - Archaeology. Report of oldest boat hints at early trade routes.

PMID- 12052938
TI  - Portraits of science. Two good women, or too good to be true?

PMID- 12052937
TI  - Evolution and development. Comparative biology joins the molecular age.

PMID- 12052939
TI  - Cancer. Targeting lymphatic metastasis.

PMID- 12052940
TI  - Geology. Flood basalts--bigger and badder.

PMID- 12052941
TI  - Statistical mechanics. Far from equilibrium.

PMID- 12052942
TI  - Immunology. T cell activation in six dimensions.

PMID- 12052943
TI  - Neuroscience. Neurons in action.

PMID- 12052944
TI  - Analytic chemistry. Everyone's a (future) chemist.
AB  - The development of small, portable "lab-on-a-chip" devices has the potential to
      provide individuals with the tools for complex chemical and biochemical analysis.
      In his Perspective, Burns charts recent progress toward fabricating such devices.
      He highlights the report by Terray et al., who use latex spheres manipulated by
      optical traps to pump fluids. The integration of such components into larger,
      more complex devices will open up applications from airborne contaminant
      detection to genetic testing and screening.

PMID- 12052945
TI  - Development. Putting the brakes on regeneration.

PMID- 12052946
TI  - A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid
      domains.
AB  - The surface membrane of cells is studded with morphologically distinct regions,
      or domains, like microvilli, cell-cell junctions, and coated pits. Each of these
      domains is specialized for a particular function, such as nutrient absorption,
      cell-cell communication, and endocytosis. Lipid domains, which include caveolae
      and rafts, are one of the least understood membrane domains. These domains are
      high in cholesterol and sphingolipids, have a light buoyant density, and function
      in both endocytosis and cell signaling. A major mystery, however, is how resident
      molecules are targeted to lipid domains. Here, we propose that the molecular
      address for proteins targeted to lipid domains is a lipid shell.

PMID- 12052947
TI  - Prehistoric decline of genetic diversity in the nene.

PMID- 12052948
TI  - Direct cortical control of 3D neuroprosthetic devices.
AB  - Three-dimensional (3D) movement of neuroprosthetic devices can be controlled by
      the activity of cortical neurons when appropriate algorithms are used to decode
      intended movement in real time. Previous studies assumed that neurons maintain
      fixed tuning properties, and the studies used subjects who were unaware of the
      movements predicted by their recorded units. In this study, subjects had real
      time visual feedback of their brain-controlled trajectories. Cell tuning
      properties changed when used for brain-controlled movements. By using control
      algorithms that track these changes, subjects made long sequences of 3D movements
      using far fewer cortical units than expected. Daily practice improved movement
      accuracy and the directional tuning of these units.

PMID- 12052949
TI  - Equilibrium information from nonequilibrium measurements in an experimental test
      of Jarzynski's equality.
AB  - Recent advances in statistical mechanical theory can be used to solve a
      fundamental problem in experimental thermodynamics. In 1997, Jarzynski proved an
      equality relating the irreversible work to the equilibrium free energy
      difference, DeltaG. This remarkable theoretical result states that it is possible
      to obtain equilibrium thermodynamic parameters from processes carried out
      arbitrarily far from equilibrium. We test Jarzynski's equality by mechanically
      stretching a single molecule of RNA reversibly and irreversibly between two
      conformations. Application of this equality to the irreversible work trajectories
      recovers the DeltaG profile of the stretching process to within k(B)T/2 (half the
      thermal energy) of its best independent estimate, the mean work of reversible
      stretching. The implementation and test of Jarzynski's equality provides the
      first example of its use as a bridge between the statistical mechanics of
      equilibrium and nonequilibrium systems. This work also extends the thermodynamic
      analysis of single molecule manipulation data beyond the context of equilibrium
      experiments.

PMID- 12052950
TI  - Direct patterning of modified oligonucleotides on metals and insulators by dip
      pen nanolithography.
AB  - The use of direct-write dip-pen nanolithography (DPN) to generate covalently
      anchored, nanoscale patterns of oligonucleotides on both metallic and insulating
      substrates is described. Modification of DNA with hexanethiol groups allowed
      patterning on gold, and oligonucleotides bearing 5'-terminal acrylamide groups
      could be patterned on derivatized silica. Feature sizes ranging from many
      micrometers to less than 100 nanometers were achieved, and the resulting patterns
      exhibited the sequence-specific binding properties of the DNA from which they
      were composed. The patterns can be used to direct the assembly of individual
      oligonucleotide-modified particles on a surface, and the deposition of multiple
      DNA sequences in a single array is demonstrated.

PMID- 12052951
TI  - Probing high-barrier pathways of surface reactions by scanning tunneling
      microscopy.
AB  - The ability of scanning tunneling microscopy to probe the pathways of thermally
      activated high-barrier surface processes is frequently limited by competing low
      barrier processes that can confuse measurement of the true initial and final
      configuration. We introduce an approach to circumvent this difficulty by driving
      the surface process with nanosecond laser heating. The method is applied to
      determine the pathway of recombinative desorption in the H/Si(001) system. The
      observed configuration of dangling bonds after laser heating reveals that the
      desorbed hydrogen molecules are not formed on single dimers, but rather from
      neighboring silicon dimers via an interdimer reaction pathway.

PMID- 12052952
TI  - Microfluidic control using colloidal devices.
AB  - By manipulating colloidal microspheres within customized channels, we have
      created micrometer-scale fluid pumps and particulate valves. We describe two
      positive-displacement designs, a gear and a peristaltic pump, both of which are
      about the size of a human red blood cell. Two colloidal valve designs are also
      demonstrated, one actuated and one passive, for the direction of cells or small
      particles. The use of colloids as both valves and pumps will allow device
      integration at a density far beyond what is currently achievable by other
      approaches and may provide a link between fluid manipulation at the macro- and
      nanoscale.

PMID- 12052953
TI  - The origin of Cu/Au ratios in porphyry-type ore deposits.
AB  - Microanalysis of major and trace elements in sulfide and silicate melt inclusions
      by laser-ablation inductively coupled plasma mass spectrometry indicates a direct
      link between a magmatic sulfide liquid and the composition of porphyry-type ore
      deposits. Copper (Cu), gold (Au), and iron (Fe) are first concentrated in a
      sulfide melt during magmatic evolution and then released to an ore-forming
      hydrothermal fluid exsolved late in the history of a magma chamber. The
      composition of sulfide liquids depends on the initial composition and source of
      the magma, but it also changes during the evolution of the magma in the crust.
      Magmatic sulfide melts may exert the dominant direct control on the economic
      metal ratios of porphyry-type ore deposits.

PMID- 12052954
TI  - 40Ar/39Ar dates from the West Siberian Basin: Siberian flood basalt province
      doubled.
AB  - Widespread basaltic volcanism occurred in the region of the West Siberian Basin
      in central Russia during Permo-Triassic times. New 40Ar/39Ar age determinations
      on plagioclase grains from deep boreholes in the basin reveal that the basalts
      were erupted 249.4 +/- 0.5 million years ago. This is synchronous with the bulk
      of the Siberian Traps, erupted further east on the Siberian Platform. The age and
      geochemical data confirm that the West Siberian Basin basalts are part of the
      Siberian Traps and at least double the confirmed area of the volcanic province as
      a whole. The larger area of volcanism strengthens the link between the volcanism
      and the end-Permian mass extinction.

PMID- 12052955
TI  - Sharp sides to the African superplume.
AB  - Beneath southern Africa is a large structure about 1200 kilometers across and
      extending obliquely 1500 kilometers upward from the core-mantle boundary with a
      shear velocity reduction of about 3%. Using a fortuitous set of SKS phases that
      travel along its eastern side, we show that the boundary of the anomaly appears
      to be sharp, with a width less than 50 kilometers, and is tilted outward from its
      center. Dynamic models that fit the seismic constraints have a dense chemical
      layer within an upwardly flowing thermal structure. The tilt suggests that the
      layer is dynamically unstable on geological time scales.

PMID- 12052956
TI  - Polytype distribution in circumstellar silicon carbide.
AB  - The inferred crystallographic class of circumstellar silicon carbide based on
      astronomical infrared spectra is controversial. We have directly determined the
      polytype distribution of circumstellar SiC from transmission electron microscopy
      of presolar silicon carbide from the Murchison carbonaceous meteorite. Only two
      polytypes (of a possible several hundred) were observed: cubic 3C and hexagonal
      2H silicon carbide and their intergrowths. We conclude that this structural
      simplicity is a direct consequence of the low pressures in circumstellar outflows
      and the corresponding low silicon carbide condensation temperatures.

PMID- 12052957
TI  - Germline stem cells anchored by adherens junctions in the Drosophila ovary
      niches.
AB  - How stem cells are recruited to and maintained in their niches is crucial to
      understanding their regulation and use in regenerative medicine. Here, we
      demonstrate that DE-cadherin-mediated cell adhesion is required for anchoring
      germline stem cells (GSCs) in their niches in the Drosophila ovary. Two major
      components of this adhesion process, DE-cadherin and Armadillo/beta-catenin,
      accumulate at high levels in the junctions between GSCs and cap cells, one of the
      niche components. Removal of these proteins from GSCs results in stem cell loss.
      Furthermore, DE-cadherin is required for recruiting GSCs to their niche. Our
      study demonstrates that anchorage of GSCs in their niche by DE-cadherin-mediated
      adhesion is important for stem cell maintenance and function.

PMID- 12052958
TI  - Homologies in leaf form inferred from KNOXI gene expression during development.
AB  - KNOTTEDI-like homeobox (KNOXI) genes regulate development of the leaf from the
      shoot apical meristem (SAM) and may regulate leaf form. We examined KNOXI
      expression in SAMs of various vascular plants and found that KNOXI expression
      correlated with complex leaf primordia. However, complex primordia may mature
      into simple leaves. Therefore, not all simple leaves develop similarly, and final
      leaf morphology may not be an adequate predictor of homology.

PMID- 12052959
TI  - Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion
      cells.
AB  - The central nervous system (CNS) loses the ability to regenerate early during
      development, but it is not known why. The retina has long served as a simple
      model system for study of CNS regeneration. Here we show that amacrine cells
      signal neonatal rat retinal ganglion cells (RGCs) to undergo a profound and
      apparently irreversible loss of intrinsic axon growth ability. Concurrently,
      retinal maturation triggers RGCs to greatly increase their dendritic growth
      ability. These results suggest that adult CNS neurons fail to regenerate not only
      because of CNS glial inhibition but also because of a loss of intrinsic axon
      growth ability.

PMID- 12052960
TI  - Trans-synaptic Eph receptor-ephrin signaling in hippocampal mossy fiber LTP.
AB  - The site of induction of long-term potentiation (LTP) at mossy fiber-CA3 synapses
      in the hippocampus is unresolved, with data supporting both pre- and postsynaptic
      mechanisms. Here we report that mossy fiber LTP was reduced by perfusion of
      postsynaptic neurons with peptides and antibodies that interfere with binding of
      EphB receptor tyrosine kinases (EphRs) to the PDZ protein GRIP. Mossy fiber LTP
      was also reduced by extracellular application of soluble forms of B-ephrins,
      which are normally membrane-anchored presynaptic ligands for the EphB receptors.
      The application of soluble ligands for presynaptic ephrins increased basal
      excitatory transmission and occluded both tetanus and forskolin-induced synaptic
      potentiation. These findings suggest that PDZ interactions in the postsynaptic
      neuron and trans-synaptic interactions between postsynaptic EphB receptors and
      presynaptic B-ephrins are necessary for the induction of mossy fiber LTP.

PMID- 12052961
TI  - Dynamic imaging of T cell-dendritic cell interactions in lymph nodes.
AB  - T cell immune responses begin within organized lymphoid tissues. The pace,
      topology, and outcomes of the cellular interactions that underlie these responses
      have, so far, been inferred from static imaging of sectioned tissue or from
      studies of cultured cells. Here we report dynamic visualization of antigen
      specific T cells interacting with dendritic cells within intact explanted lymph
      nodes. We observed immunological synapse formation and prolonged interactions
      between these two cell types, followed by the activation, dissociation, and rapid
      migration of T cells away from the antigenic stimulus. This high-resolution
      spatiotemporal analysis provides insight into the nature of cell interactions
      critical to early immune responses within lymphoid structures.

PMID- 12052962
TI  - Dynamics of thymocyte-stromal cell interactions visualized by two-photon
      microscopy.
AB  - Thymocytes are selected to mature according to their ability to interact with
      self major histocompatibility complex (MHC)-peptide complexes displayed on the
      thymic stroma. Using two-photon microscopy, we performed real-time analysis of
      the cellular contacts made by developing thymocytes undergoing positive selection
      in a three-dimensional thymic organ culture. A large fraction of thymocytes
      within these cultures were highly motile. MHC recognition was found to increase
      the duration of thymocyte-stromal cell interactions and occurred as both long
      lived cellular associations displaying stable cell-cell contacts and as shorter,
      highly dynamic contacts. Our results identify the diversity and dynamics of
      thymocyte interactions during positive selection.

PMID- 12052963
TI  - Activation of endothelial cell protease activated receptor 1 by the protein C
      pathway.
AB  - The coagulant and inflammatory exacerbation in sepsis is counterbalanced by the
      protective protein C (PC) pathway. Activated PC (APC) was shown to use the
      endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease
      activated receptor 1 (PAR1) on endothelial cells. Gene profiling demonstrated
      that PAR1 signaling could account for all APC-induced protective genes, including
      the immunomodulatory monocyte chemoattractant protein-1 (MCP-1), which was
      selectively induced by activation of PAR1, but not PAR2. Thus, the prototypical
      thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a
      role for this receptor cascade in protection from sepsis.

PMID- 12052964
TI  - Worsening in ischemic stroke patients: is it time for a new strategy?

PMID- 12052965
TI  - Brain hemorrhage after thrombolysis: good or bad?

PMID- 12052967
TI  - Acute stroke trials: strengthening the underpowered.

PMID- 12052966
TI  - Use of selective serotonin reuptake inhibitors and the risk of stroke: is there
      reason for concern?

PMID- 12052968
TI  - Hyperhomocysteinemia, MTHFR 677C-->T polymorphism, and stroke.

PMID- 12052969
TI  - Helicobacter pylori, CagA-positive strains, and ischemic stroke.

PMID- 12052970
TI  - Influenza virus infection, infectious burden, and atherosclerosis.

PMID- 12052971
TI  - Testing the ICH score.

PMID- 12052972
TI  - When is a stroke actually "stable"?

PMID- 12052973
TI  - Microbleeding on MRI as a marker for hemorrhage after stroke thrombolysis.

PMID- 12052974
TI  - Outcomes in carotid endarterectomy performed by vascular surgeons or
      neurosurgeons.

PMID- 12052975
TI  - Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal
      arterial ischemic stroke among young adults.
AB  - BACKGROUND AND PURPOSE: The etiology of arterial ischemic stroke (AIS) in the
      young remains unknown in one third of patients. Serum paraoxonase (PON1) is an
      HDL-associated esterase that hydrolyzes products of lipid peroxidation and
      prevents the oxidation of LDL. Two common polymorphisms in the PON1 gene, the 192
      Gln (Q) --> Arg (R) and 55 Leu (L) --> Met (M) substitutions, determine
      interindividual variation in PON1 activity. The association of these
      polymorphisms with the risk of AIS remains controversial. METHODS: We analyzed
      118 patients (64 women) with a first nonfatal AIS occurring <45 years of age and
      118 1:1 age (+/-2 years)- and sex-matched controls. The PON1 polymorphisms were
      determined by polymerase chain reaction amplification and restriction digestion.
      RESULTS: The prevalence of the PON1 192RR genotype (P=0.006) and the frequency of
      the R allele (P=0.010) were significantly increased among young AIS patients
      compared with controls. After adjustment for conventional vascular and
      prothrombotic risk factors, the 192RR genotype remained independently associated
      with a 4-fold increase in the risk of AIS (odds ratio=4.1; 95% CI, 1.14 to
      14.73). Subanalyses stratified by the presence of vascular risk factors and
      ethnicity did not significantly modify the effect of the PON1 192 polymorphism on
      AIS risk. No significant differences were found between patients and controls
      regarding the PON1 55 polymorphism. CONCLUSIONS: These findings suggest that the
      PON 192RR genotype is independently associated with an increased risk of nonfatal
      AIS among young adults. Further studies are necessary to understand better the
      mechanistic implications of these observations in the development of AIS in the
      young.

PMID- 12052976
TI  - Selective serotonin reuptake inhibitors and the risk of stroke: a population
      based case-control study.
AB  - BACKGROUND AND PURPOSE: Selective serotonin reuptake inhibitors (SSRIs) have been
      associated with increased risk of bleeding complications, possibly as a result of
      inhibition of platelet aggregation. Little is known about the risk of
      intracerebral hemorrhage in users of SSRIs and whether the effect on platelet
      aggregation reduces the risk of ischemic stroke. We used population-based data to
      estimate the risk of hemorrhagic and ischemic stroke in users of SSRIs. METHODS:
      We performed a nested case-control study in Funen County (465 000 inhabitants),
      Denmark. All patients with a first-ever stroke discharge diagnosis in the period
      of 1994 to 1999 were identified, and a validated diagnosis of stroke was reached
      in 4765 cases. In all, 40 000 controls were randomly selected from the background
      population. Information on drug use for cases and controls was retrieved from a
      prescription registry with full coverage of the county. Odds ratios were adjusted
      for age, sex, calendar year, and use of other medication. To evaluate the effect
      of various potential confounders not recorded in the register data, we performed
      separate analyses on data from 2 large population-based surveys with more
      detailed information on risk factors. RESULTS: Of 659 patients with hemorrhagic
      stroke, 21 were current users of SSRIs. The adjusted odds ratio of hemorrhagic
      stroke in current SSRI users compared with never users was 1.0 [95% confidence
      interval (CI), 0.6 to 1.6]. Of 2717 patients with ischemic stroke, 100 were
      current users of SSRIs, and the adjusted odds ratio of ischemic stroke in cases
      compared with controls was 1.1 (95% CI, 0.9 to 1.4). The survey data indicated
      that additional confounder control would not have led to an increase in the
      relative risk estimates. CONCLUSIONS: Current exposure to SSRIs is not associated
      with increased risk of intracerebral hemorrhage and is probably not associated
      with a decreased risk of ischemic stroke.

PMID- 12052977
TI  - Chlamydia pneumoniae seropositivity is associated with increased plasma levels of
      soluble cellular adhesion molecules in community-dwelling subjects: the Shimanami
      Health Promoting Program (J-SHIPP) study.
AB  - BACKGROUND AND PURPOSE: In vitro studies have demonstrated that Chlamydia
      pneumoniae infection of the endothelium increases the expression of adhesion
      molecules and chemokines, indicating that C pneumoniae infection affects the
      adhesion and recruitment of leukocytes to the endothelium, which is believed to
      be involved in the initial steps of atherosclerosis. However, whether chronic C
      pneumoniae infection increases these molecules in vivo has not been elucidated.
      METHODS: The association between C pneumoniae seropositivity and plasma
      concentrations of soluble adhesion molecules and a chemokine was investigated in
      200 community-dwelling residents free from cardiovascular diseases and
      medication. Plasma levels of IgA and IgG antibodies to C pneumoniae were measured
      by enzyme-linked immunosorbent assay. Indices of IgG and IgA antibodies were
      determined as the ratio to the standardized positive control. The subjects were
      divided into 3 groups according to the indices of antibodies: C pneumoniae
      seronegative (n=57, IgA<1.0 and IgG<1.0), C pneumoniae intermediate (n=81, 1.0<
      or =IgA> or =1.1 or 1.0< or =IgG> or =1.1), and C pneumoniae seropositive (n=62,
      IgA>1.1 and IgG>1.1). Plasma concentrations of soluble forms of intercellular
      adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1, and monocyte
      chemoattractant protein-1 were determined by enzyme-linked immunosorbent assay.
      RESULTS: Plasma concentrations of ICAM-1 (392+/-118, 398+/-94, 470+/-154 ng/mL,
      P=0.0004) and vascular cellular adhesion molecule-1 (402+/-146, 419+/-130, 472+/
      181 ng/mL, P=0.03) were significantly different among the C pneumoniae
      seronegative, intermediate, and seropositive groups respectively. However, plasma
      monocyte chemoattractant protein-1 was not significantly different among the 3
      groups. Stepwise regression analysis showed that plasma concentration of ICAM-1
      was significantly associated with C pneumoniae seropositivity, independent of
      other known risk factors for atherosclerosis and carotid intima-media thickness.
      CONCLUSION: These findings indicate that C pneumoniae seropositivity is
      associated with higher plasma concentrations of soluble forms of adhesion
      molecules in the general population. The increase in circulating adhesion
      molecules may underlie the mechanisms linking C pneumoniae infection and
      atherosclerosis in vivo.

PMID- 12052978
TI  - Parallel morning and evening surge in stroke onset, blood pressure, and physical
      activity.
AB  - BACKGROUND AND PURPOSE: A circadian variation with a morning peak on waking and
      arising is known to occur in both blood pressure (BP) and cardiovascular event
      onset. A second peak in BP has been described to occur after an afternoon sleep
      (siesta). This study was designed to investigate the hypothesis that the 2-peak
      diurnal variation of BP is dependent on physical activity and occurs in parallel
      with the diurnal variation of stroke onset. METHODS: The diurnal variation of
      stroke onset was compared with the diurnal variation of BP, pulse rate (PR), and
      physical activity in 3 independent groups of Greek hypertensives 51 to 80 years
      of age (633 stroke patients, 379 subjects with 24-hour ambulatory BP monitoring,
      and 50 subjects with 24-hour physical activity monitoring through wrist devices).
      RESULTS: The diurnal variation of stroke onset, BP, and PR all showed 1 morning
      and 1 evening peak with a decline in the afternoon and at night that occurred in
      parallel with the diurnal variation in physical activity (P<0.001 for differences
      among morning, afternoon, evening, and nighttime intervals in BP, PR, activity,
      and stroke). The afternoon decline in BP, PR, and activity was significant only
      in subjects with a siesta. CONCLUSIONS: The 2-peak diurnal variation in stroke
      onset occurred in parallel with the variation in BP, PR, and physical activity.
      These data support the hypothesis that an abrupt change in physical activity is
      not only a major determinant of the 2-peak diurnal variation of BP but also an
      important triggering factor for a cerebrovascular event.

PMID- 12052979
TI  - Retinal microvascular abnormalities and cognitive impairment in middle-aged
      persons: the Atherosclerosis Risk in Communities Study.
AB  - BACKGROUND AND PURPOSE: Cerebral microvascular disease has been hypothesized to
      contribute to cognitive impairment, but few clinical data are available. Here, we
      examine the relation of retinal microvascular abnormalities with cognitive
      function in middle-aged persons free of stroke. METHODS: The Atherosclerosis Risk
      in Communities Study is a population-based study with examinations every 3 years
      from 1987 through 1998. At visit 3, when participants were 51 to 70 years of age,
      retinal photographs were obtained and evaluated for retinal microvascular
      abnormalities according to standardized protocols. Cognitive function was
      assessed with standardized tests (Delayed Word Recall Test, Digit Symbol Subtest,
      and Word Fluency Test) at visits 2 and 4 and averaged for analysis. Persons with
      stroke or taking central nervous system-relevant medications were excluded,
      leaving 8734 with data for this study. RESULTS: After education, diabetes
      mellitus, blood pressure, carotid intima-media thickness, and other risk factors
      were controlled for, retinopathy was associated with lower cognitive test scores.
      The adjusted odds ratios for persons with Delayed Word Recall scores 2 SD or
      lower than the mean were 2.60 [95% confidence interval (CI), 1.30 to 2.91] for
      any retinopathy, 3.00 (95% CI, 1.81 to 4.98) for microaneurysms, 3.39 (95% CI,
      1.99 to 5.78) for retinal hemorrhage, and 3.07 (95% CI, 1.53 to 6.17) for soft
      exudates. Results were similar for the other 2 cognitive tests and in people with
      and without diabetes and hypertension. CONCLUSIONS: Retinopathy is independently
      associated with poorer cognitive function in middle-aged persons without stroke,
      suggesting that cerebral microvascular disease may contribute to the development
      of cognitive impairment.

PMID- 12052980
TI  - Association of plasma homocysteine concentration with atherosclerotic carotid
      plaques and lacunar infarction.
AB  - BACKGROUND AND PURPOSE: Higher plasma total homocysteine (tHcy) levels have been
      associated with carotid atherosclerosis and cerebral infarction in whites.
      However, data regarding such associations are limited for Asians. This study
      examined associations between tHcy levels and severity of carotid atherosclerosis
      in Japanese subjects. Additionally, because lacunar infarction is the most
      prevalent type of ischemic stroke in Japan, we also investigated its associations
      with tHcy levels. METHODS: The subjects were 152 Japanese patients (age, 66.2+/
      11.0 years) at our hospital. Using ultrasound, we evaluated severity of carotid
      atherosclerosis by plaque score, which is defined by the sum of all plaque
      (intima-media thickness > or =1.1 mm) height in bilateral carotid arteries. In
      112 of 152 patients, the existence of lacunar infarction was evaluated on brain
      MRI scans. RESULTS: A moderate linear association was found between tHcy levels
      and plaque score (r=0.48, P<0.0001). Moreover, tHcy level was associated with
      plaque score (beta=0.26, P<0.001) independently of traditional atherosclerotic
      risk factors. In logistic regression analyses, each 1-micromol/L-higher tHcy
      level was associated with a 1.37-fold-higher [95% confidence interval (CI), 1.19
      to 1.58] likelihood for lacunar infarction, increasing the likelihood by 1.22
      fold (95% CI, 1.04 to 1.43) independently of traditional atherosclerotic risk
      factors. CONCLUSIONS: Higher tHcy levels appear to have associations with
      increased severity of carotid atherosclerotic plaques and prevalent lacunar
      infarction in the Japanese. Larger prospective studies are necessary to establish
      whether higher tHcy levels serve as a harbinger for insidious carotid and
      cerebrovascular diseases.

PMID- 12052981
TI  - Predominant involvement of ipsilateral anterior and posterior circulations in
      moyamoya disease.
AB  - BACKGROUND AND PURPOSE: We encountered several patients with childhood onset of
      moyamoya disease in whom the ipsilateral anterior and posterior circulations were
      predominantly involved. This study investigated whether this is an angiographic
      characteristic of this disease. METHODS: We evaluated steno-occlusive lesions on
      angiograms of 85 patients with pediatric onset of moyamoya disease, using two 4
      stage angiographic classification scales for the internal carotid artery and
      posterior cerebral artery systems (ICA and PCA staging, respectively) and
      determined whether lesions with more advanced ICA and PCA stages were on
      ipsilateral sides. RESULTS: When positive laterality was defined as the presence
      of a difference by > or =1 stage between the stages on both sides, lateralities
      in the ICA stages and in the PCA stages were present in 40 (47%) and 27 patients
      (32%), respectively. Lesions with more advanced ICA and PCA stages were on the
      same side, with significant probability (P=0.024, Fisher's exact test).
      Lateralities in both ICA and PCA lesions were found in 17 patients. In 14 (82%)
      of the 17 patients, the more advanced side of ICA lesions was the same as that of
      PCA lesions, while it was contralateral in 3 patients (18%). CONCLUSIONS: In
      pediatric-onset moyamoya disease, asymmetrical involvement of bilateral ICAs and
      PCAs was common, and the ipsilateral ICA and PCA tended to be predominantly
      involved.

PMID- 12052982
TI  - Observer agreement in the angiographic assessment of arteriovenous malformations
      of the brain.
AB  - PURPOSE: We aimed to determine intraobserver and interobserver agreement in the
      characterization of brain arteriovenous malformation (AVM) angioarchitecture on
      intra-arterial digital subtraction angiograms. METHODS: Five experienced
      interventional neuroradiologists independently reviewed 40 anonymized angiograms
      obtained at the time of first-ever AVM diagnosis. The allocation of the films to
      observers was balanced for AVM size and complexity. Every observer was compared
      with himself and all the others by distributing the films in 2 batches 3 months
      apart. The observers used standard forms to collect both quantitative and
      categorized qualitative angiographic data. To measure agreement we used the kappa
      statistic (kappa) for nominal data, weighted kappa for ordinal and discrete
      interval data, and Bland & Altman analysis for continuous data. RESULTS:
      Intraobserver agreement was generally moderate to substantial, with 95%
      confidence intervals ranging from fair to almost perfect. However, for every
      characteristic, interobserver agreement was less than intraobserver agreement.
      Interobserver agreement was generally slight to moderate, with 95% confidence
      intervals ranging from less than chance to almost perfect. CONCLUSION: This study
      demonstrates the need for robust and generalizeable definitions of AVM
      angioarchitecture and methods of nidus size measurement-with proof of good
      intraobserver and interobserver agreement-for future efforts to understand the
      prognosis and best treatment of AVMs.

PMID- 12052983
TI  - Lacunar stroke is the major cause of progressive motor deficits.
AB  - BACKGROUND AND PURPOSE: Severe motor deficits are the predominant cause of long
      term disability in stroke patients. In particular, progressive hemiparesis in the
      initial stage after stroke onset is frequently devastating. Therefore, we
      attempted to define the population at risk with respect to the presumed
      pathogenesis. METHODS: Among 941 stroke patients hospitalized during a 3-year
      period, 92 patients (41 men, 51 women; mean age, 68 years) had a severe motor
      deficit (<25 of 42 points on the 7 motor items of the European Stroke Scale)
      resulting from brain infarcts. Risk factors, neurological examinations,
      comprehensive diagnostic tests, and therapy were documented. The study population
      was separated into patients with (group A) and without (group B) progressive
      motor deficits. Progression was defined as a further decrease of at least 5
      points on the initial European Stroke Scale motor score during the first 5 days
      after stroke onset. RESULTS: Of the 92 patients, 23.9% had significant worsening
      of motor function with a decrease in the mean European Stroke Scale motor score
      from 20.3 to 12.9 points (P<0.01). Infarcts in group A patients were subcortical
      in 59.1%, whereas most infarcts were cortical in group B (61.4%, P<0.05).
      Progressive hemiparesis was also significantly associated with lacunar stroke
      (group A:, 59.1%; group B, 24.3%; P<0.01). With regard to risk factors,
      diagnostic studies, and neuroimaging, small-vessel disease was the predominant
      presumed cause of stroke in group A (63.6%, P<0.01), whereas infarcts in group B
      patients were frequently caused by embolism from cardiac or undetermined sources
      (61.4%, P<0.01). Prevalence of high-grade carotid stenosis was not significantly
      different between groups A and B; however, subtotal stenoses and complete
      internal carotid artery occlusions were found only among patients without
      progressive motor deficits. CONCLUSIONS: Lacunar stroke caused by small-vessel
      disease is the major cause of progressive motor deficits, probably because of
      stepwise occlusion of the branches of small penetrating arteries.

PMID- 12052984
TI  - Increased anisotropy in acute stroke: a possible explanation.
AB  - BACKGROUND AND PURPOSE: The increase in fractional anisotropy (FA) in acute
      stroke has yet to be explained. Using an engineering methodology known as pq
      diagrams, we sought to explain the increase in FA by describing changes in the
      total magnitude of the diffusion tensor (L) as well as the isotropic (p) and
      anisotropic (q) components. METHODS: Diffusion tensor imaging was performed in 10
      patients with stroke <27 hours old. The diffusion tensor was decomposed into the
      p and q components and plotted to describe the diffusion trajectories. FA was
      also calculated and compared. RESULTS: There was significant and consistent
      reduction in p, q, and L (p: mean, -50.0%; range, -36.6% to -64.5%; q: mean, 
      50.8%; range, -30.8% to -72.8%; L: mean, -50.3%; range, -37.0% to -65.1%). There
      were inconsistent changes in FA (mean, -0.5%; range, -44.9% to +45.0%). Five
      patients had elevated FA due to proportionately higher loss of L than q.
      CONCLUSIONS: Changes in FA only occur when there is a change in the ratio of q/L.
      Acute elevation of FA occurred in the context of a larger reduction in L than q.
      The elevation in FA occurs in the context of a reduction in the anisotropic
      tensor and therefore is a consequence of ratio-metric measurement. This appears
      to clarify the reported increase in FA in terms of alterations in the shape of
      the apparent diffusion tensor. pq diagrams appear to offer improved resolution of
      acute diffusion changes in ischemia.

PMID- 12052985
TI  - High-resolution, contrast-enhanced magnetic resonance angiography with elliptical
      centric k-space ordering of supra-aortic arteries compared with selective X-ray
      angiography.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to evaluate the relative
      value of high-resolution, contrast-enhanced MR angiography (CE MRA) with
      elliptical centric k-space ordering compared with intra-arterial x-ray
      angiography for imaging carotid stenosis. METHODS: Thirty patients with suspected
      stenosis of the carotid arteries were examined with CE MRA (1.5-T scanner) and x
      ray angiography (aortic arch survey and selective imaging of both common carotid
      arteries). For the first time, not only the extracranial carotid bifurcation but
      all the vessel segments from the aortic arch to the circle of Willis were
      assessed by independent investigators. RESULTS: For the internal carotid artery
      in the region of the extracranial carotid bifurcation, there was a very close
      correlation between CE MRA and x-ray angiography (sensitivity, 100%; specificity,
      92%). The initially suspected overestimation of stenosis on CE MRA in 3 cases was
      ultimately revealed to be an underestimation on x-ray angiography. CE MRA showed
      slightly poorer imaging of the basal vessel segments at the level of the aortic
      arch (because of breathing artifacts) and the intracranial vessel segments
      (because of small vessel caliber and venous superimposition due to delayed
      sequence starts). CONCLUSIONS: The MRA technique described here provides reliable
      results in the diagnosis of carotid stenosis and is thus suitable for replacing
      the invasive conventional x-ray angiography method in most cases. Further
      technical developments with regard to spatial resolution are still required for
      improved visualization of small vessels (terminal carotid branches and
      intracranial vessels).

PMID- 12052986
TI  - Second harmonic imaging of the human brain: the practicability of coronal
      insonation planes and alternative perfusion parameters.
AB  - BACKGROUND AND PURPOSE: Second harmonic imaging (SHI) is a novel ultrasound
      technique that allows the evaluation of brain tissue perfusion. The purpose of
      this study was to assess normal cerebral echo contrast characteristics in 3
      regions of interest (ROIs) in the transverse axial and coronal insonation planes
      through the temporal bone window. Materials and Methods- SHI examinations were
      performed in 25 patients without cerebrovascular disease (aged 50+/-19 years) in
      a transverse axial and a coronal diencephalic insonation plane through the
      temporal bone window. After intravenous administration of 2.5 g (400 mg/mL) of a
      galactose-based echo contrast agent, 62 time-triggered images with a transmission
      rate of 1 frame per 2.5 seconds were recorded for offline analysis. Time
      intensity curves, including peak intensity (PI) (dB) and positive gradient (PG)
      (dB/s), were calculated to quantify ultrasound intensity in 3 different ROIs in
      both planes of the following sections: the thalamus (ROI(thal)), the lentiform
      nucleus (ROI(ncl)), and the area supplied by the middle cerebral artery
      (ROI(mca)). RESULTS: Characteristic time-intensity curves with high PIs and steep
      PGs were recorded in each ROI. Statistical analysis of the aforementioned
      parameters showed no significant difference for comparison of the 3 ROIs in the
      transverse axial versus the coronal insonation plane. Comparison of different
      ROIs in the transverse axial insonation plane revealed that PI was significantly
      higher in ROI(thal) than in ROI(mca) (7.8 versus 5.5 dB; P<0.05) and
      significantly higher in ROI(ncl) than in ROI(thal) (9.3 versus 7.8 dB; P<0.05).
      In contrast, PG was comparable in ROI(thal) and in ROI(mca) (0.21 versus 0.25
      dB/s; P=0.42). CONCLUSIONS: SHI is a promising technique for the evaluation of
      cerebral parenchymal perfusion. Comparison of the transverse axial and coronal
      insonation planes shows similar time-intensity curves with comparable values for
      PIs and PGs. Coronal insonation allows the evaluation of perfusion abnormalities
      near the vertex and skull base, areas that cannot be depicted in the transverse
      axial plane. Comparison of the different ROIs indicates that the PG is a more
      robust and reliable parameter than the PI.

PMID- 12052987
TI  - Silent cerebral microbleeds on T2*-weighted MRI: correlation with stroke subtype,
      stroke recurrence, and leukoaraiosis.
AB  - BACKGROUND AND PURPOSE: Gradient-echo T2*-weighted MRI is uniquely sensitive to
      detect silent, old hemosiderin deposits, but the clinical significance of such
      "microbleeds" remains to be determined. Therefore, we investigated the incidence
      and the number of microbleeds among different stroke subtypes and the correlation
      with stroke recurrence and the severity of leukoaraiosis. METHODS: This study
      consisted of 213 patients (73.5+/-9.1 years old, 104 men and 109 women), who were
      classified according to stroke subtypes into atherothrombotic infarction (24
      patients), cardioembolic infarction (23 patients), lacunar infarction (66
      patients), intracerebral hemorrhage (35 patients), and control (65 patients)
      groups. Gradient-echo T2*-weighted MRI was performed with a 1.5 T system, and
      asymptomatic microbleeds were located and counted. RESULTS: The incidence and the
      number of microbleeds were significantly greater in patients with intracerebral
      hemorrhage (71.4% and 9.1+/-13.8, respectively) and lacunar infarction (62.1% and
      7.4+/-16.1) compared with patients with cardioembolic infarction (30.4% and 2.5+/
      5.6), atherothrombotic infarction (20.8% and 0.63+/-1.53), and controls (7.7% and
      0.09+/-0.34). There was a correlation between the number of microbleeds and the
      severity of periventricular hyperintensity (r=0.626, P<0.0001). There was also a
      correlation between the number of microbleeds and the number of intracerebral
      hemorrhages (r=0.689, P<0.0001) or lacunar infarctions (r=0.514, P<0.0001). The
      locations of microbleeds were subcortical white matter (31.8%), thalamus (24.8%),
      basal ganglia (19.8%), brain stem (12.0%), and cerebellum (11.7%). CONCLUSIONS:
      The findings suggest that microbleeds on T2*-weighted MRI are an indicator of
      advanced small artery disease of the brain with an increased risk for bleeding.
      This result should be taken into consideration when treating patients with
      stroke, and further studies are required.

PMID- 12052988
TI  - Small centrum ovale infarcts on diffusion-weighted magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: A small centrum ovale infarct (SCOI), caused by occlusion
      of the white matter medullary arteries, is often equated with a lacunar infarct.
      We sought to clarify the clinical characteristics of a SCOI visualized by
      diffusion-weighted MRI (DWI) compared with those of a small basal ganglia infarct
      (SBGI). METHODS: Patients with a SCOI (SCOI group; n=38) or SBGI (SBGI group;
      n=68) < or =15 mm in diameter on conventional MRI and DWI were selected from 582
      consecutive patients with acute ischemic stroke. Sex, age, neurological symptoms,
      vascular risk factors, emboligenic heart disease, arterial occlusive disease in
      the ipsilateral carotid system, and recurrent stroke within the initial 30 days
      were compared between the 2 groups. RESULTS: Only 47% of SCOIs but 87% of SBGIs
      could be identified with the use of conventional MRI, whereas DWI could detect
      them all. Age, sex, and vascular risk factors were not significantly different
      between the 2 groups. The SCOI group had more frequently an abrupt onset of
      symptoms (63% versus 26%; P=0.0002), emboligenic heart diseases (34% versus 12%;
      P=0.0054), occlusive carotid and/or middle cerebral artery diseases (53% versus
      19%; P=0.0004), and recurrent stroke (13% versus 1%; P=0.0216) but less
      frequently a classic lacunar syndrome (50% versus 81%; P=0.0009) than the SBGI
      group. On a multivariate analysis, both arterial and heart diseases were
      independently associated with the SCOI group. CONCLUSIONS: Symptomatic SCOIs
      detected by DWI may be associated with large-vessel and heart diseases and should
      be distinguished from lacunar infarcts.

PMID- 12052989
TI  - Heterogeneity of stroke pathophysiology and neuroprotective clinical trial
      design.
AB  - BACKGROUND AND PURPOSE: Tissue substrates for action of neuroprotective agents
      may be absent in a significant proportion of strokes. Pathophysiological
      heterogeneity is a possible contributor to negative neuroprotective trials.
      METHODS: Stroke subtypes and their individual outcomes in neuroprotective trial
      control populations were used to derive models incorporating accuracy of clinical
      classification and probability of an ischemic penumbra. With the use of treatment
      effect sizes from successful trials (predominantly of reperfusion therapies),
      sample sizes for neuroprotective trials were calculated. The potential influence
      of altered recruitment strategies was explored. RESULTS: The proportion of
      informative patients in 2 large neuroprotective trials was probably only 27% to
      30%. Optimistically, this proportion may be 50%; pessimistically, it may be only
      17%. These figures necessitate a sample size of 3700 to 4500 subjects per group;
      at best, 1800 to 2200 are needed per group with optimistic assumptions about
      treatment effect. Strategies to enhance the proportion with tissue substrate for
      neuroprotection could reduce sample size to 500 per group and simultaneously
      reduce the total number of patients screened compared with inclusive trials.
      CONCLUSIONS: Population heterogeneity alone may be sufficient to explain negative
      neuroprotective trials because even in the largest trials to date sample size is
      inadequate to detect effect size equivalent to those with thrombolysis, and it is
      possible that they have been severely underpowered. Reliable trials with
      inclusive entry criteria may be too large to be commercially feasible for novel
      compounds. Both sample size and total number of patients needing to be screened
      should be reduced by restricting entry to patients more likely to have a tissue
      target.

PMID- 12052990
TI  - Thrombolysis-related hemorrhagic infarction: a marker of early reperfusion,
      reduced infarct size, and improved outcome in patients with proximal middle
      cerebral artery occlusion.
AB  - BACKGROUND AND PURPOSE: The role of early and delayed recanalization after
      thrombolysis in the development of hemorrhagic transformation (HT) subtypes
      remains uncertain. We sought to explore the association between the timing of
      recanalization and HT risk in patients with proximal middle cerebral artery (MCA)
      occlusion treated with intravenous recombinant tissue plasminogen activator
      (rtPA) <3 hours of stroke onset and to investigate the relationship between HT
      subtypes, infarct volume, and outcome. METHODS: Thirty-two patients with acute
      stroke caused by proximal MCA occlusion treated with rtPA <3 hours of symptom
      onset were prospectively studied. Serial transcranial Doppler examinations were
      performed on admission and at 6, 12, 24, and 48 hours. Presence and type of HT
      were assessed on CT at 36 to 48 hours. Modified Rankin scale was used to assess
      outcome at 3 months. RESULTS: Early and delayed recanalization was identified in
      17 patients (53.1%) and 8 patients (25%), respectively. HT was detected in 14
      patients (43.7%): 4 (12.5%) with hemorrhagic infarction (HI1), 5 (15.6%) with
      HI2, 3 (9.3%) with parenchymal hematoma (PH1), and 2 (6.8%) with PH2.
      Distribution of HT subtypes differed significantly (P=0.025), depending on the
      time to artery reopening. Eight of 9 (89%), 1 of 5 (20%), and 8 of 18 (44.4%)
      with HI1-HI2, with PH1-PH2, and without HT, respectively, recanalized in <6
      hours. Delayed recanalization was observed in 1 patient with HI1-HI2 (11%), 4
      with PH1-PH2 (80%), and 3 without HT (16.6%). Neurological improvement was
      significantly (P<0.001) more frequent in patients with HI1-HI2 (88%) than in
      those without HT (39%). Infarct volume was significantly (P<0.031) lower in
      patients with HI1-HI2 (51.4+/-42 cm3) than in patients with PH1-PH2 (83.8+/-48
      cm3) and those without HT (98.4+/-84 cm3, P=0.021). The modified Rankin scale
      score was significantly lower in HI1-HI2 compared with PH1-PH2 patients (1.9+/
      1.1 versus 4.6+/-1.2, P<0.001) and with those without HT (1.9+/-1.1 versus 3.5+/
      2.0, P=0.009.). CONCLUSIONS: Thrombolysis-related HI (HI1-HI2) represents a
      marker of early successful recanalization, which leads to a reduced infarct size
      and improved clinical outcome.

PMID- 12052991
TI  - Computed tomographic findings in patients undergoing intra-arterial thrombolysis
      for acute ischemic stroke due to middle cerebral artery occlusion: results from
      the PROACT II trial.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the role of
      noncontrast CT in the selection of patients to receive thrombolytic therapy for
      acute ischemic stroke and to predict radiological and clinical outcomes. METHODS:
      One hundred eighty patients with stroke due to middle cerebral artery (MCA)
      occlusion were randomized 2:1 within 6 hours of onset to receive intra-arterial
      recombinant prourokinase plus intravenous heparin or intravenous heparin only.
      Four hundred fifty-four CT examinations were digitized to calculate early infarct
      changes, infarct volumes, and hemorrhagic changes among the 162 patients treated
      as randomized (108 recombinant prourokinase-treated patients and 54 control
      patients). CT changes were correlated with baseline stroke severity, angiographic
      clot location, collateral vessels, and outcome at 90 days. RESULTS: Baseline CT
      scans, 120 (75%) of 159, showed early infarct-related abnormalities. The baseline
      CT abnormality volume was not correlated with the baseline National Institutes of
      Health Stroke Scale (NIHSS) score (r=-0.11) but was correlated weakly with the
      outcome (r=0.17, P<0.05). Compared with patients with M2 occlusions, patients
      with M1 MCA occlusions had significantly higher baseline NIHSS scores (P<0.05),
      more basal ganglia involvement on CT, and larger hypodensity volumes on follow-up
      CTs. Compared with patients with partial or no collateral supply, patients with
      full collateral supply had lower baseline NIHSS scores, significantly smaller
      baseline CT infarct volumes, and less cortical involvement (P<0.05). CONCLUSIONS:
      Noncontrast CT is not correlated with baseline stroke severity and does not
      predict outcome in patients with stroke due to MCA occlusion. However, baseline
      CT changes, clinical presentation, and the evolution of CT changes are influenced
      by clot location and the presence of a collateral supply.

PMID- 12052993
TI  - Use of intravenous heparin by North American neurologists: do the data matter?
AB  - BACKGROUND AND PURPOSE: Our aim was to determine current usage patterns of
      intravenous heparin for patients with acute ischemic stroke. METHODS: A survey
      was undertaken of 280 neurologists from the United States and 270 neurologists
      from Canada. Brief vignettes were presented for the following 5 scenarios: stroke
      in evolution, atrial fibrillation-related stroke (A FIB), vertebrobasilar stroke,
      carotid territory stroke, and multiple transient ischemic attacks. The effect of
      medicolegal factors was also ascertained. Statistical comparisons were done with
      chi-squared testing. RESULTS: US neurologists were significantly more likely than
      Canadian neurologists to use intravenous heparin for patients with stroke in
      evolution (51% versus 33%, P<0.001), vertebrobasilar stroke (30% versus 8%,
      P<0.001), carotid territory stroke (31% versus 4%, P<0.001), and multiple
      transient ischemic attacks (47% versus 9%, P<0.001). The vast majority of US and
      Canadian neurologists would use intravenous heparin for acute stroke patients
      with A FIB (88% and 84%, respectively). US neurologists more often cited
      medicolegal factors as a potential influence on the decision-making process than
      Canadian neurologists (33% versus 10%, P<0.001). CONCLUSIONS: In several clinical
      scenarios, US neurologists were significantly more likely than Canadian
      neurologists to use intravenous heparin. Fears regarding medicolegal consequences
      may partially explain the treatment disparity. Despite the publication of 4
      clinical trials, which have not shown any long-term benefit for patients with
      acute stroke and A FIB (International Stroke Trial, Heparin in Acute Embolic
      Stroke Trial) or cardioembolic stroke (Trial of Org 10172 in Acute Stroke
      Treatment, the Tinzaparin in Acute Ischemic Stroke Trial), both US and Canadian
      neurologists would use intravenous heparin in large numbers for this condition.
      Further studies are warranted to investigate the lack of impact of "negative"
      studies on clinician behavior.

PMID- 12052992
TI  - Plasma vitamin C modifies the association between hypertension and risk of
      stroke.
AB  - BACKGROUND AND PURPOSE: There are no prospective studies to determine whether
      plasma vitamin C modifies the risk of stroke among hypertensive and overweight
      individuals. We sought to examine whether plasma vitamin C modifies the
      association between overweight and hypertension and the risk of stroke in middle
      aged men from eastern Finland. METHODS: We conducted a 10.4-year prospective
      population-based cohort study of 2419 randomly selected middle-aged men (42 to 60
      years) with no history of stroke at baseline examination. A total of 120 men
      developed a stroke, of which 96 were ischemic and 24 hemorrhagic strokes.
      RESULTS: Men with the lowest levels of plasma vitamin C (<28.4 micromol/L, lowest
      quarter) had a 2.4-fold (95% CI, 1.4 to 4.3; P=0.002) risk of any stroke compared
      with men with highest levels of plasma vitamin C (>64.96 micromol/L, highest
      quarter) after adjustment for age and examination months. An additional
      adjustment for body mass index, systolic blood pressure, smoking, alcohol
      consumption, serum total cholesterol, diabetes, and exercise-induced myocardial
      ischemia attenuated the association marginally (relative risk, 2.1; 95% CI, 1.2
      to 3.8; P=0.01). Adjustment for prevalent coronary heart disease and atrial
      fibrillation did not attenuate the association any further. Furthermore,
      hypertensive men with the lowest vitamin C levels (<28.4 micromol/L) had a 2.6
      fold risk (95% CI, 1.52 to 4.48; P<0.001), and overweight men (> or =25 kg/m2)
      with low plasma vitamin C had a 2.7-fold risk (95% CI, 1.48 to 4.90; P=0.001) for
      any stroke after adjustment for age, examination months, and other risk factors.
      CONCLUSIONS: Low plasma vitamin C was associated with increased risk of stroke,
      especially among hypertensive and overweight men.

PMID- 12052994
TI  - Multidisciplinary management of spinal dural arteriovenous fistulas: clinical
      presentation and long-term follow-up in 49 patients.
AB  - BACKGROUND AND PURPOSE: In the early 1980s, it was demonstrated that surgical
      intradural division of the shunting vein to the medullary venous plexus cures a
      spinal dural arteriovenous fistula (DAVF) at low morbidity. There is, however,
      growing literature to support endovascular therapy. METHODS: The clinical
      features of 49 consecutive patients with a spinal DAVF treated at a single
      institution between 1986 and 2001 were studied (mean age, 63 years; range, 28 to
      78 years; 80% male). When possible, embolization was offered as the initial
      treatment. Endovascular treatment was considered adequate only if the proximal
      shunting vein could be occluded with liquid adhesive embolics. Motor and bladder
      function was evaluated with Aminoff scores an average of 32.3 months after
      treatment. RESULTS: All but 1 patient presented with myelopathy. At a mean of 2.3
      years after symptom onset, 48 DAVFs were angiographically demonstrated. Since
      1999, gadolinium-enhanced MR angiography was additionally performed in 7 patients
      to point out the level of the DAVF. Endovascular embolization could be attempted
      in 44 of the 48 DAVFs and resulted in a cure in 11 (25%). Thirty-five DAVFs were
      surgically cured; 2 patients refused surgery after failed embolization.
      Angiographic confirmation of the treatment result was available in 97.7% of the
      patients. No permanent complications of either embolization or surgery were
      noted. Motor and bladder function scores were significantly improved in 35
      patients who had long-term follow-up (both P<0.005). CONCLUSIONS: Endovascular
      treatment with liquid adhesive material provided a result equal to surgery in 25%
      of patients, overall resulting in a significant amelioration in the neurological
      status of patients with a spinal DAVF.

PMID- 12052995
TI  - Hemicraniectomy and moderate hypothermia in patients with severe ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We compared the clinical course of 36 consecutive
      patients with severe acute ischemic stroke (more than two thirds of the middle
      cerebral artery territory) treated with hemicraniectomy (CE; n=17) or moderate
      hypothermia (MH; n=19) in terms of intracranial pressure control, mortality, and
      specific treatment parameters. METHODS: Over a period of 18 months, patients with
      severe ischemic stroke were treated with CE when the nondominant hemisphere was
      affected and with MH when the dominant hemisphere was affected. MH (33 degrees C)
      was induced with either cold blankets and fans (n=11) or endovascular cooling
      (n=8). Intracranial pressure was monitored invasively in all cases. RESULTS: Age,
      sex, cranial CT findings, level of consciousness, and time to treatment were
      similar between the 2 groups; significant differences were noted in National
      Institute of Health Stroke Scale (NIHSS) score (20 [range, 18 to 22] and 17
      [range, 16 to 18] for MH and CE, respectively) but were not present when NIHSS
      score was corrected for aphasia (17 [range, 15 to 19] and 17 [range, 16 to 18]
      for MH and CE, respectively). Mortality was 12% for CE and 47% for MH; 1 patient
      treated with MH died as a result of treatment complications (sepsis) and 3 of
      intracranial pressure crises that occurred during rewarming. Duration of
      mechanical ventilation and of neurological intensive care unit stay did not
      significantly differ, but duration of catecholamine application and maximal
      catecholamine dosage were significantly higher in the MH group. CONCLUSIONS: In
      patients with severe ischemic stroke, CE results in lower mortality and lower
      complication rates compared with MH. Both treatment modalities, however, are
      associated with intensive medical treatment and a prolonged stay in the
      neurological intensive care unit.

PMID- 12052996
TI  - Two coupled motor recovery protocols are better than one: electromyogram
      triggered neuromuscular stimulation and bilateral movements.
AB  - BACKGROUND AND PURPOSE: Overcoming chronic hemiparesis from a cerebrovascular
      accident (CVA) can be challenging for many patients, especially after the first
      12 months after the CVA. With the use of established motor control theories, the
      present study investigated electromyogram (EMG)-triggered neuromuscular
      stimulation and bilateral coordination training. METHODS: Twenty-five CVA
      subjects volunteered to participate in this motor recovery protocol study.
      Subjects were randomly assigned to 1 of 3 groups: (1) coupled protocol of EMG
      triggered stimulation and bilateral movement (n=10); (2) EMG-triggered
      stimulation and unilateral movement (n=10); or (3) control (n=5). All
      participants completed 6 hours of rehabilitation during a 2-week period according
      to group assignments. Motor capabilities of the wrist and fingers were evaluated
      on the basis of 3 categories of motor tasks in a pretest-posttest control group
      design. RESULTS: Significant findings for the (1) number of blocks moved in a
      functional task, (2) chronometric reaction times to initiate movements, and (3)
      sustained muscle contraction capability all favored the coupled bilateral
      movement training and EMG-triggered neuromuscular stimulation protocol group. In
      addition, the unilateral movement/stimulation group exceeded the control group in
      the number of blocks moved and rapid onset of muscle contractions. CONCLUSIONS:
      This new evidence is convincing in that subjects in the coupled protocol group
      were able to demonstrate enhanced voluntary motor control across 3 categories of
      tasks. Chronic hemiparesis decreased considerably in the wrist and fingers as CVA
      patients expanded their motor repertoire.

PMID- 12052997
TI  - Direct costs of modern treatment of aneurysmal subarachnoid hemorrhage in the
      first year after diagnosis.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate the current
      direct costs of modern management of patients with aneurysmal subarachnoid
      hemorrhage in the first year after diagnosis. METHODS: During a 1-year period, we
      studied all admitted patients with subarachnoid hemorrhage from a population of 2
      million people. We calculated the direct costs of treatment, which included the
      costs of medical and nursing care and the related travel expenses of patients. We
      calculated true costs for all major healthcare resources. National census data,
      if available, and standard charges were used to determine healthcare resource
      expenses. RESULTS: Hospital admissions and diagnostic and therapeutic
      interventions in 110 patients accounted for 85% of all costs; 64% of the total
      direct medical costs during admission were the medical, nursing, and overhead
      costs alone. Patients discharged directly to home generated 4% of the total
      budget, whereas admission to a nursing home accounted for the remaining 11% of
      the total costs. Of the diagnostic and therapeutic costs, 45% was caused by
      imaging and 42% by surgery or coiling. Angiography alone accounted for 52% of the
      total imaging costs and 24% of the total diagnostic and therapeutic costs.
      Prescribed medication accounted for only 3% of the total budget of diagnostic and
      therapeutic costs. CONCLUSIONS: Most direct costs during the first year after
      aneurysmal subarachnoid hemorrhage are caused by the hospital inpatient days,
      accounting for two thirds of the total costs generated during the first year
      after the initial bleeding. If new costly treatments succeed in reducing the
      average length of inpatient hospital stays, then progress in therapy may prove
      cost effective and might even be cost saving.

PMID- 12052998
TI  - Integrated care pathways and quality of life on a stroke rehabilitation unit.
AB  - BACKGROUND AND PURPOSE: Integrated care pathways (ICP) may not reduce disability,
      institutionalization, or duration of hospitalization compared with conventional
      multidisciplinary team (MDT) care in organized stroke rehabilitation. Their
      potential to improve patient heath status or satisfaction with care is not known.
      METHODS: A comparison of quality of life, caregiver strain, and patient/caregiver
      satisfaction at 6 months after stroke was undertaken in 152 stroke patients
      randomized to receive ICP or MDT care. Differences in processes of care were
      recorded with the use of a predefined schedule. Multivariate analyses were
      undertaken to identify the effect of age, sex, stroke severity, functional
      status, mood, and use of care pathway on quality of life score. RESULTS: The 2
      groups were comparable for baseline characteristics of age, sex, stroke severity,
      and initial disability. MDT care was characterized by greater emphasis on return
      of higher function and caregiver needs compared with ICP. EuroQol Visual Analogue
      Scale (EQ-VAS) scores were higher in the MDT group (median, 72 versus 63;
      P<0.005), who also had higher scores for EuroQol dimension of social functioning
      (P=0.014). Higher EQ-VAS scores were independently related to MDT care (P=0.04),
      Rankin score (P=0.01), and psychological function (P<0.0001) but not to age, sex,
      or stroke severity. There were no significant differences in patient or caregiver
      satisfaction between the 2 settings. CONCLUSIONS: Better quality of life in
      patients receiving conventional MDT care may be attributable to improved social
      functioning and greater attention to higher function and caregiver needs during
      rehabilitation.

PMID- 12052999
TI  - Societal costs of vascular cognitive impairment in older adults.
AB  - BACKGROUND AND PURPOSE: The construct of vascular cognitive impairment (VCI)
      includes many whose care is or will be costly. Nevertheless, estimates of these
      costs are not well described. We therefore set out to estimate the societal costs
      of VCI in elderly people. METHODS: In a secondary analysis of the Canadian Study
      of Health and Aging, a representative cohort study, Canadian dollar costs using a
      societal perspective were estimated by standard methods. RESULTS: The total
      annual per-patient societal costs for VCI by severity were $15 022 for those with
      mild disease, $14 468 for those with mild to moderate disease, $20 063 for those
      with moderate disease, and $34 515 for those with severe disease. The most
      expensive component per individual was the cost of institutional long-term care.
      Although severe impairment was associated with higher costs, the extent of
      institutionalization at all levels of severity and less drug use among those more
      severely impaired mitigated a severity-cost gradient. CONCLUSIONS: The societal
      costs of VCI are not inconsiderable. In contrast to Alzheimer disease, there is
      no clear gradient relating cost to severity. Unpaid caregiver costs are an
      important aspect of societal costs, even in those with only mild impairment.

PMID- 12053000
TI  - Longitudinal study of motor recovery after stroke: recruitment and focusing of
      brain activation.
AB  - BACKGROUND AND PURPOSE: The goal of this study was to characterize cortical
      reorganization after stroke and its relation with the site of the stroke-induced
      lesion and degree of motor recovery using functional MRI (fMRI). METHODS:
      Fourteen stroke patients with an affected upper limb were studied longitudinally.
      Three fMRI sessions were performed over a period of 1 to 6 months after stroke.
      Upper limb recovery, Wallerian degeneration of the pyramidal tract, and responses
      to transcranial magnetic stimulation were assessed. RESULTS: Two main patterns of
      cortical reorganization were found. Pattern 1 was focusing, in which, after
      initial recruitment of additional ipsilateral and contralateral areas, activation
      gradually developed toward a pattern of activation restricted to the
      contralateral sensorimotor cortex in 9 patients. Five patients were found to have
      pattern 2, persistent recruitment, in which there was an initial and sustained
      recruitment of ipsilateral activity. Occurrence of recruitment or focusing seemed
      to depend mainly on whether the primary motor cortex (M1) was lesioned;
      persistent recruitment was observed in 3 of 4 patients with M1 injury, and
      focusing was seen in 8 of 10 patients with spared M1. These patterns had no
      relation to the degree of recovery; in particular, focusing did not imply
      recovery. However, there was a clear relation between the degree of recovery and
      the degree of Wallerian degeneration. CONCLUSIONS: These results suggest that
      ipsilateral recruitment after stroke corresponds to a compensatory
      corticocortical process related to the lesion of the contralateral M1 and that
      the process of compensatory recruitment will persist if M1 is lesioned;
      otherwise, it will be transient.

PMID- 12053001
TI  - Increased risk for postoperative hemorrhage after intracranial surgery in
      patients with decreased factor XIII activity: implications of a prospective
      study.
AB  - BACKGROUND AND PURPOSE: The functional integrity of the hemostatic system is a
      prerequisite for the safe performance of neurosurgical procedures. To monitor the
      individual coagulation capacity of each patient, standard tests are effective to
      detect deficiencies involving the generation of fibrin. However, fibrin clot
      strength depends primarily on coagulation factor XIII, which cross-links fibrin
      monomers and enhances clot resistance against fibrinolysis. Therefore, factor
      XIII is functionally involved in both the hemostatic and fibrinolytic systems.
      The objective of this prospective study was to determine the incidence and
      clinical relevance of perioperative decreased factor XIII with respect to
      standard coagulation parameters and the occurrence of postoperative hematoma.
      METHODS: In 876 patients, 910 neurosurgical procedures were performed.
      Prothrombin time (PT), partial thromboplastin time (PTT), platelet count,
      fibrinogen, and factor XIII were tested in each patient preoperatively and
      postoperatively. RESULTS: Postoperative intracranial hematoma (defined as
      requiring surgical evacuation) occurred after 39 (4.3%) of 910 surgical
      procedures. Patients with postoperative hematoma had significantly lower factor
      XIII and fibrinogen levels preoperatively and postoperatively than patients
      without hematoma. In patients with postoperative hematoma, PT and platelets
      differed significantly only postoperatively, whereas PTT was different neither
      preoperatively nor postoperatively. Of the 39 patients with a postoperative
      hematoma, 13 (33.3%) had a postoperative factor XIII <60% compared with 61 (7%)
      of 867 patients without hematoma (P<0.01, Fisher's exact test). The relative risk
      of developing a postoperative hematoma is therefore increased 6.4-fold in
      patients with postoperative factor XIII <60%. The risk is increased 12-fold in
      patients who additionally have postoperative decreased fibrinogen levels (<1.5
      g/L) and 9-fold in patients with platelet count <150x10(9)/L and factor XIII
      <60%. CONCLUSIONS: This is the first prospective study that demonstrates the
      association of decreased perioperative factor XIII with an increased risk of
      postoperative hematoma in neurosurgical patients. The risk is further increased
      in those patients with low factor XIII and additional abnormalities of
      fibrinogen, PT, platelets, and PTT. Factor XIII testing and specific replacement,
      as accepted for other clotting factors, may reduce the risk of postoperative
      hematoma.

PMID- 12053002
TI  - Stroke in Lund-Orup, Sweden: improved long-term survival among elderly stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Several studies report declining early stroke case
      fatality, but the findings are not consistent across geographic areas.
      Corresponding changes in long-term survival are less well documented. We recently
      reported increased stroke incidence among patients aged <75 years and stable
      incidence among older persons. We now report temporal trends for early and late
      case fatality among patients with stroke onset during 1983-1985 and 1993- 1995.
      METHODS: Patients living within the Lund-Orup, Sweden, hospital district and
      fulfilling the diagnostic criteria for first-ever stroke during 1983-1985 (n=998)
      and 1993-1995 (n=1318) were followed up concerning survival status at 28 days, 1
      year, and 3 years. Age and sex adjustments were performed. The possible influence
      of Oxfordshire Community Stroke Project (OCSP) stroke subtypes on survival was
      also analyzed. RESULTS: Overall survival improved between the study periods (Cox
      proportional hazards regression: hazard ratio, 0.84; 95% confidence limits, 0.75
      to 0.94; P=0.0019). The 28-day case fatality was 15% for stroke patients from
      both study periods. One-year case fatality was 31% for 1983-1985 patients and 27%
      for 1993-1995 patients. The corresponding figures at 3 years were 44% and 40%,
      respectively. In the group aged <75 years, there were no significant changes in
      overall survival, but survival improved significantly among patients aged > or =
      75 years beyond 28 days after stroke onset. OCSP stroke subtype was an
      independent predictor of death (P<0.0001). CONCLUSIONS: The recently observed
      increase in stroke incidence among patients aged <75 years was not accompanied by
      changing survival in that age group. However, among patients aged > or =75 years,
      survival improved beyond 28 days after stroke. The causes of this change in
      survival are unknown but may be related to improved long-term care of elderly
      stroke patients.

PMID- 12053003
TI  - Does renal dysfunction predict mortality after acute stroke? A 7-year follow-up
      study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to investigate renal
      function as a long-term predictor of mortality in patients hospitalized for acute
      stroke. METHODS: This was a cohort study done in a Scottish tertiary teaching
      hospital. Participants included 2042 (993 male) unselected consecutive stroke
      patients (mean age, 73 years) admitted to hospital within 48 hours of stroke
      between 1988 and 1994. Follow-up was up to 7 years. Main outcome measure was all
      cause mortality. RESULTS: The total number of deaths at the end of follow-up was
      1026. Most subjects (1512) had creatinine <124 micromol/L. The mean calculated
      creatinine clearance was 54.8 mL/min (SD, 23 mL/min). Renal function indexes were
      analyzed by quartiles with Cox proportional-hazards model. Stroke survivors had
      higher calculated creatinine clearance and lower serum creatinine, urea, and
      ratios of urea to creatinine. Calculated creatinine clearance > or =51.27 mL/min
      significantly predicted better long-term survival in these stroke patients even
      after adjustment for confounders (age, neurological score, ischemic heart
      disease, hypertension, smoking, and diuretic use). Similarly, creatinine > or
      =119 micromol/L "relative risk (RR), 1.59; 95% confidence interval (CI), 1.32 to
      1.92", urea 6.8 to 8.9 mmol/L (RR, 1.34; 95% CI, 1.09 to 1.65) or > or =9 mmol/L
      (RR, 1.74; 95% CI, 1.42 to 2.13), and ratio of urea to creatinine > or =0.08573
      mmol/micromol (RR, 1.24; 95% CI, 1.03 to 1.50) remained significant predictors of
      mortality after adjustment for confounders. CONCLUSIONS: After acute stroke,
      patients with reduced admission calculated creatinine clearance, raised serum
      creatinine and urea concentrations (even within conventional reference
      intervals), and raised ratio of urea to creatinine had a higher mortality risk.
      This finding may be used to stratify risk and target interventions, eg, the use
      of angiotensin-converting enzyme inhibitors.

PMID- 12053004
TI  - Cerebrovascular disease and evolution of depressive symptoms in the
      cardiovascular health study.
AB  - BACKGROUND AND PURPOSE: Previous studies have reported an association between
      cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study
      (CHS) provides an opportunity to examine the relationship between vascular brain
      pathology seen on neuroimaging and changes in depressive symptoms. METHODS: The
      sample included 3236 CHS participants who had an MRI brain scan. Demographic
      variables, medical history, functional status, and apolipoprotein E genotype were
      obtained at baseline. Annual scores on a modified version of the Centers for
      Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to
      7 years subsequently. RESULTS: After controlling for important covariates,
      occurrence of depressive symptoms (defined as modified CES-D score of >7) was
      associated with small lesions in the basal ganglia, large cortical white-matter
      lesions, and severe subcortical white-matter grade. Neuroimaging variables did
      not predict incident depression among those who were nondepressive at the time of
      MRI. Persistence of depressive symptoms across 2 consecutive time points was
      associated with small basal ganglia lesions and large cerebral cortical white
      matter lesions. Worsening of depression (increase in CES-D score of > or =5) was
      associated with subcortical white-matter lesions. CONCLUSIONS: These findings
      suggest that cerebrovascular disease at baseline is related to depression
      symptoms over time. Further studies are needed to investigate the differential
      effects of subcortical white- versus gray-matter lesions on mood.

PMID- 12053005
TI  - Intracranial venous hemodynamics is a factor related to a favorable outcome in
      cerebral venous thrombosis.
AB  - BACKGROUND: In recent studies, coma, cerebral hemorrhage, older age, and
      infectious origin have been identified as prognostic factors in cerebral venous
      thrombosis (CVT). However, no studies of the prognosis of CVT have evaluated
      hemodynamic factors. However, it is conceivable that the presence or absence and
      the efficiency of venous collaterals, as well as recanalization, may have an
      impact on brain tissue damage and hence on the prognosis of acute CVT. METHODS:
      Twenty-six patients with acute CVT (mean age, 40+/-15 years) were recruited
      prospectively. All patients were treated with intravenous heparin, followed by
      oral anticoagulation for 12 months, except for 2 patients who were lost to follow
      up after hospital discharge. Neurological deficits were graded on the National
      Institute of Health Stroke Scale on admission, at hospital discharge, and at 90+/
      14 days after admission. The functional clinical outcome was graded on the
      modified Rankin Scale on day 90 after admission. All patients received a venous
      transcranial duplex sonography (TCCS) on admission and were followed up in case
      of a pathological result until normalization was recorded (mean follow-up, 316+/
      395 days; range, 13 to 1180 days). RESULTS: Initial TCCS was pathological in 18
      of 26 patients (69%). Four distinct venous drainage types were identified:
      increased drainage to the cavernous sinus and to the deep cerebral veins, flow
      reversal in the basal veins, and either compensatory increased or reversed flow
      in the transverse sinus. Initially normal venous TCCS or normalized TCCS within
      90 days was significantly related to favorable outcome. CONCLUSIONS: TCCS can be
      used to evaluate venous drainage patterns in acute CVT. Furthermore, initially
      normal and normalization of initially pathological venous TCCS within 90 days is
      related to a favorable outcome in this disease.

PMID- 12053006
TI  - Prognostic importance of leukoaraiosis in patients with symptomatic internal
      carotid artery stenosis.
AB  - BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is a frequent finding on brain CT
      scans. This study examined patients with LA and symptomatic internal carotid
      artery disease. METHODS: Patients in the North American Symptomatic Carotid
      Endarterectomy Trial were evaluated for the extent of LA. Long-term prognosis and
      perioperative risk associated with carotid endarterectomy were assessed. RESULTS:
      Among 2618 patients, 493 had LA: 354 restricted and 139 widespread. Patients with
      LA were older, had a history of hypertension, had more hemispheric ischemic
      events (particularly stroke), and had small, deep brain infarcts. The 3-year
      risks of stroke for medically treated patients were 20.2% (no LA), 27.3%
      (restricted LA), and 37.2% (widespread LA) (P=0.01). For surgically treated
      patients, the risks were 14.2%, 25.4%, and 33.6%, respectively (P<0.001). With
      widespread LA, occurrence of disabling strokes doubled in medical patients and
      tripled in surgical patients. The 30-day perioperative risks of any stroke or
      death for surgical patients with 50% to 99% internal carotid artery stenosis were
      5.3% (no LA), 10.6% (restricted LA), and 13.9% (widespread LA). Despite higher
      perioperative risk, endarterectomy reduced the absolute 3-year risk of stroke
      ipsilateral to the symptomatic 50% to 99% stenosed artery by 11.6% (P=0.46) for
      patients with widespread LA, 7.6% (P=0.39) with those with restricted LA, and
      10.9% (P<0.001) for those with no LA. CONCLUSIONS: In patients with a transient
      ischemic attack or nondisabling stroke associated with internal carotid artery
      disease, presence of LA was associated with an increased risk of any stroke and
      of disabling or fatal stroke. Patients with widespread LA had the worst
      prognosis. Despite the higher perioperative risk, endarterectomy reduced the risk
      of stroke.

PMID- 12053007
TI  - How well are hypertension, hyperlipidemia, diabetes, and smoking managed after a
      stroke or transient ischemic attack?
AB  - BACKGROUND AND PURPOSE: Stroke prevention clinics (SPCs) are not usually involved
      with the active management of hypertension, hyperlipidemia, diabetes, and
      smoking. The effect of consultations generated at SPCs on the adequacy of the
      management of these risk factors for stroke has not been well described, and few
      studies have long-term follow-up. METHODS: We performed a prospective study of
      119 consecutive patients referred to an SPC for secondary prevention. One year
      after their baseline visit, patients were re-evaluated for the adequacy of the
      management of the above risk factors, and the proportion of improvement was
      assessed. RESULTS: One-hundred twelve patients returned for their 1-year follow
      up visit. Sixty-six were male, and the average age was 65 years. Hypertension was
      present in 83 patients, hyperlipidemia in 92, diabetes in 26, and smoking in 38,
      and 80 had multiple risk factors. At baseline, 66% of patients with hypertension,
      17% of patients with hyperlipidemia, and 23% of diabetics had adequate management
      of their respective risk factors. During 1 year of follow-up, hypertension
      management improved 20% (P<0.001) and lipid management improved 32% (P<0.001).
      There was no significant improvement in diabetes management or smoking cessation.
      CONCLUSIONS: Although our understanding of the benefit of addressing
      hypertension, hyperlipidemia, diabetes, and smoking for secondary prevention of
      stroke is evolving, we found marked room for improvement in the management of
      these four risk factors. SPCs may need to be more actively involved in the
      management of these modifiable risk factors, if we are to significantly impact
      the risk of recurrent stroke.

PMID- 12053008
TI  - Social stress exacerbates focal cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to determine whether
      exposure to stress or elevated corticosterone concentrations in the days
      preceding cerebral ischemia exacerbates ischemic injury as assessed by
      histological and behavioral outcomes. METHODS: For 7 consecutive days, male
      C57/BL6 mice were exposed to social stress for 45 minutes or injected with 1
      mg/kg corticosterone or vehicle. The animals exposed to social stress were
      injected with either 1 mg/kg mifepristone, a glucocorticoid receptor antagonist,
      or the vehicle 30 minutes before stress. On the seventh day, all animals were
      trained in a passive avoidance task. Twenty-four hours after training, the
      animals were subjected to 60 minutes of intraluminal middle cerebral artery
      occlusion (MCAO) or sham surgery. At 72 hours of reperfusion, the animals were
      tested for retention of the passive avoidance task, and infarction size was
      determined. RESULTS: Animals subjected to chronic social stress or treated with
      exogenous corticosterone before MCAO exhibited larger infarcts and reduced
      retention of passive avoidance compared with the nonstressed MCAO control. The
      effects of social stress on infarct volume and passive avoidance were reversed by
      pretreatment with mifepristone. There was no difference between stressed and
      control groups in physiological parameters or reduction of laser-Doppler flow
      signal during MCAO or reperfusion. CONCLUSIONS: Prior exposure to social stress
      increases infarction volume and exacerbates cognitive deficits associated with
      transient cerebral ischemia. The mechanism underlying the effects of stress on
      stroke outcome likely involves corticosterone acting through glucocorticoid
      receptors to increase subsequent ischemia-induced neuronal death.

PMID- 12053009
TI  - Effects of the spin trap agent disodium- [tert-butylimino)methyl]benzene-1,3
      disulfonate N-oxide (generic NXY-059) on intracerebral hemorrhage in a rabbit
      Large clot embolic stroke model: combination studies with tissue plasminogen
      activator.
AB  - BACKGROUND AND PURPOSE: It has been proposed that the novel spin trap agent
      disodium-[(tert-butylimino)methyl]benzene-1,3-disulfonate N-oxide (NXY-059) may
      be useful in the treatment of ischemia and stroke. To date, there is little
      information concerning the safety of NXY-059 when administered in combination
      with the only Food and Drug Administration-approved pharmacological agent for the
      treatment of stroke, the thrombolytic tissue plasminogen activator (tPA). Thus,
      we determined the effects of NXY-059G, a generic form of NXY-059, on hemorrhage
      and infarct rate and volume when administered alone or in combination with tPA.
      In addition, we determined whether NXY-059G affected 2 physiological variables,
      blood glucose levels and body temperature. METHODS: Male New Zealand White
      rabbits were embolized by injecting a large blood clot into the middle cerebral
      artery via a catheter. Five minutes after embolization, NXY-059G (100 mg/kg) was
      infused intravenously; control rabbits received infusions of saline, the vehicle
      required to solubilize NXY-059G. In tPA studies, the thrombolytic was
      administered intravenously starting 60 minutes after embolization (20% bolus
      injection/80% infusion over 30 minutes). Body temperature and blood glucose
      levels were measured throughout the study. Postmortem analysis included
      assessment of hemorrhage and infarct rate, size, and location. RESULTS: In the
      vehicle control group, the hemorrhage rate after a thromboembolic stroke was 52%
      (n=23), and this was increased by 67% if tPA was administered (n=15). The rabbits
      treated with NXY-059G in the absence of tPA had a 79% incidence of hemorrhage
      (n=19), an increase of 52% over the control group. In the combination drug
      treated groups, the NXY-059G/tPA group had a 47% incidence of hemorrhage (n=15).
      There was a decrease of hemorrhage volume in the NXY-059G+tPA group compared with
      the other 3 groups included in the study. There was no significant effect of NXY
      059G either alone or in combination with tPA on infarct rate or volume. NXY-059G
      did not significantly alter the physiological variables that were measured.
      CONCLUSIONS: This study suggests that NXY-059G may affect the integrity of the
      cerebral vasculature when administered immediately after an embolic stroke, as
      evidenced by an increase in hemorrhage rate. However, when NXY-059G is
      administered in combination with tPA, it may improve the safety of tPA by
      reducing the incidence of tPA-induced hemorrhage. The mechanism(s) involved in
      the NXY-059G-induced increase in hemorrhage rate and reduction of tPA-induced
      hemorrhage rate remains to be elucidated.

PMID- 12053010
TI  - Sympathetic nervous activity and myocardial damage immediately after subarachnoid
      hemorrhage in a unique animal model.
AB  - BACKGROUND AND PURPOSE: Obvious cardiac dysfunction, including ECG abnormalities
      and left ventricular asynergy, is known to develop after subarachnoid hemorrhage
      (SAH). To clarify the close relationship between myocardial damage and
      sympathetic nervous activity immediately after SAH, a novel experimental animal
      model was used. METHODS: SAH was provoked by perforation of the basilar artery
      with the use of a microcatheter inserted through the femoral artery in 18 beagle
      dogs. Hemodynamic changes were recorded, and plasma concentrations of
      noradrenaline, adrenaline, and 3-methoxy-4-hydroxy-phenylethylene glycol (MHPG)
      and serum levels of creatine kinase-MB (CK-MB) and troponin T were measured at 0,
      5, 15, 30, 60, 120, and 180 minutes after SAH. RESULTS: Noradrenaline (pg/mL),
      adrenaline (pg/mL), and MHPG (ng/mL) increased abruptly from 120+/-70, 130+/-70,
      and 1.3+/-0.5 before SAH to 1700+/-1200, 5600+/-3500, and 3.2+/-1.2 at 5 minutes
      after SAH, respectively. Aortic pressure, left ventricular wall motion, and
      cardiac output increased by 60%, 40%, and 30%, respectively (P<0.001) at 5
      minutes and then decreased by 50%, 55%, and 40%, respectively (P<0.001) >60
      minutes after SAH compared with baseline values. The peak value of CK-MB
      correlated positively with the peak values of noradrenaline and adrenaline
      (r=0.730 and r=0.611, respectively). The peak value of troponin T also correlated
      positively with the peak values of noradrenaline and adrenaline (r=0.828 and
      r=0.792, respectively). CONCLUSIONS: These results suggest that the elevated
      activity of the sympathetic nervous system observed in the acute phase of SAH
      induced myocardial damage and contributed to the development of cardiac
      dysfunction.

PMID- 12053011
TI  - Neuroprotection and P450 2C11 upregulation after experimental transient ischemic
      attack.
AB  - BACKGROUND AND PURPOSE: Transient ischemic attack (TIA) is a risk factor for
      stroke. However, TIA may also serve as a preconditioning stimulus, reducing
      damage from subsequent stroke. We tested the hypothesis that experimental TIA
      induces expression of P450 2C11, an arachidonic acid epoxygenase that produces
      vasodilator epoxyeicosatrienoic acids, leading to increased tissue perfusion and
      reduced stroke damage. METHODS: Wistar rats underwent three 10-minute middle
      cerebral artery occlusions (TIA) or sham surgery. Three days later, animals were
      subjected to 2-hour middle cerebral artery occlusion and 24 hours of reperfusion.
      Brains were stained with 2,3,5-triphenyltetrazolium chloride for infarct size
      measurement or processed for quantification of P450 2C11 mRNA and protein with
      the use of RNase protection assay and Western blotting. Regional cerebral blood
      flow (CBF) at the end of 2-hour ischemia was measured in separate groups of rats
      with iodoantipyrine autoradiography. RESULTS: Cerebral infarct was reduced by
      >50% in TIA- versus sham-preconditioned animals. 2C11 mRNA and protein were
      increased in ipsilateral hemisphere by 3 days after TIA but not sham surgery.
      Induction of 2C11 by TIA was also evident in ipsilateral hemisphere at 24 hours
      after 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. End
      ischemic regional CBF was not different between TIA- and sham-pretreated groups.
      CONCLUSIONS: We conclude that experimental TIA induces ischemic tolerance by a
      mechanism temporally linked to upregulation of P450 2C11. Enzyme induction does
      not attenuate ischemic severity by amplifying end-ischemic CBF.

PMID- 12053012
TI  - Estrogen increases endothelial nitric oxide synthase via estrogen receptors in
      rat cerebral blood vessels: effect preserved after concurrent treatment with
      medroxyprogesterone acetate or progesterone.
AB  - BACKGROUND AND PURPOSE: In vivo and in vitro rat models of hormone therapy were
      used to test the following hypotheses: (1) estrogen acts directly on
      cerebrovascular estrogen receptors to increase endothelial nitric oxide synthase
      (eNOS); (2) increased protein correlates with higher NOS activity; and (3)
      effects of estrogen on eNOS are altered by concurrent treatment with either
      medroxyprogesterone acetate (MPA) or progesterone. METHODS: Blood vessels were
      isolated from brains of ovariectomized female rats; some were treated for 1 month
      with estrogen, estrogen and progesterone, or estrogen and MPA. Isolated cerebral
      vessels were also treated in vitro with estrogen in the absence and presence of
      progesterone, MPA, tamoxifen, and the estrogen receptor antagonist ICI 182 780.
      Levels of eNOS were measured by Western blot, and NOS activity was measured by
      [14C]arginine-[14C]citrulline conversion. RESULTS: Chronic hormone treatment in
      vivo resulted in plasma levels of 17beta-estradiol, progesterone, and MPA in the
      range of values found in humans. Estrogen treatment resulted in higher levels of
      cerebrovascular NOS activity that paralleled increases in eNOS protein. In vitro
      estrogen treatment for 18 hours also resulted in a concentration-dependent
      increase in eNOS protein (EC50 approximately 300 pmol/L) that was completely
      prevented by estrogen receptor antagonists tamoxifen or ICI 182 780. However,
      cotreatment with progesterone or MPA, either in vivo or in vitro, did not alter
      the effect of estrogen on eNOS protein. CONCLUSIONS: Estrogen receptor activation
      in cerebrovascular tissue results in increased eNOS activity and protein levels.
      The latter effect persists in the presence of either progesterone or MPA. Thus,
      increased NO production by eNOS may contribute to the neuroprotective effects of
      estrogen.

PMID- 12053013
TI  - Inhibitory effects of protein kinase C on inwardly rectifying K+- and ATP
      sensitive K+ channel-mediated responses of the basilar artery.
AB  - BACKGROUND AND PURPOSE: The structurally related, inwardly rectifying K+ (K(IR))
      channel and the ATP-sensitive K+ (K(ATP)) channel are important modulators of
      cerebral artery tone. Although protein kinase C (PKC) activators have been shown
      to inhibit these channels with the use of patch-clamp electrophysiology, effects
      of PKC on K+ channel function in intact cerebral blood vessels are unknown. We
      therefore tested whether pharmacological alteration of PKC activity affects
      cerebral vasodilator responses to K(IR) and/or K(ATP) channel activators in vivo.
      METHODS: We measured changes in basilar artery diameter using a cranial window
      preparation in anesthetized rats. In addition, intracellular recordings of smooth
      muscle membrane potential were made in isolated basilar arteries. RESULTS: K+ (5
      to 15 mmol/L) and aprikalim (1 to 10 micromol/L) each elicited reproducible
      vasodilatation. The PKC activator phorbol-12,13-dibutyrate (PdBu) (50 nmol/L)
      inhibited responses to K+ (by 40% to 55%) and aprikalim (by 40% to 70%), whereas
      responses to papaverine were unaffected. The PKC inhibitor calphostin C (0.1
      micromol/L) augmented responses to K+ (by 2- to 3-fold) and aprikalim (2-fold)
      but not papaverine. In addition, K+ (5 mmol/L) and aprikalim (3 micromol/L) each
      hyperpolarized the basilar artery. PdBu inhibited these responses to aprikalim by
      45% but had no effect on K+-induced hyperpolarization. CONCLUSIONS: These data
      suggest that both basal and stimulated PKC activity inhibit K(IR) and K(ATP)
      channel-mediated cerebral vasodilatation in vivo. The inhibitory effect on K(ATP)
      channel-mediated vasodilatation occurs at least partly by inhibition of
      hyperpolarization mediated by K(ATP) channels. PKC inhibits K+-induced
      vasodilatation without affecting hyperpolarization, suggesting that the
      inhibitory effect of PKC on vasodilator responses to K+ does not involve altered
      K(IR) channel function.

PMID- 12053014
TI  - [3H]muscimol binding to gamma-aminobutyric acid(A) receptors is upregulated in
      CA1 neurons of the gerbil hippocampus in the ischemia-tolerant state.
AB  - BACKGROUND AND PURPOSE: Excitotoxic activation of glutamate receptors is
      currently thought to play a pivotal role in delayed neuronal death (DND) of
      highly vulnerable CA1 neurons in the gerbil hippocampus after transient global
      ischemia. Postischemic degeneration of these neurons can be prevented by
      "preconditioning" with a short sublethal ischemic stimulus. The present study was
      designed to test whether ischemic preconditioning is associated with specific
      alterations of ligand binding to excitatory glutamate and/or inhibitory gamma
      aminobutyric acid (GABA)A receptors compared with ischemia severe enough to
      induce DND. METHODS: With the use of quantitative receptor autoradiography,
      postischemic ligand binding of [3H]MK-801 and [3H]alpha-amino-3-hydroxy-5-methyl
      4-isoxazole propionic acid (AMPA) to excitatory N-methyl-D-aspartate (NMDA) and
      AMPA receptors as well as [3H]muscimol to inhibitory GABA(A) receptors in
      hippocampal subfields CA1, CA3, and the dentate gyrus were analyzed in 2
      experimental paradigms. Gerbils were subjected to (1) a 5-minute ischemic period
      resulting in DND of CA1 neurons and (2) a 2.5-minute period of ischemia mediating
      tolerance induction. RESULTS: [3H]MK-801 and [3H]AMPA binding values to
      excitatory NMDA and AMPA receptors showed a delayed decrease in relatively
      ischemia-resistant CA3 and dentate gyrus despite maintained neuronal cell
      density. [3H]Muscimol binding to GABA(A) receptors in CA1 neurons was transiently
      but significantly increased after preconditioning but not after global ischemia
      with consecutive neuronal death. CONCLUSIONS: Downregulation of ligand binding to
      glutamate receptors in relatively ischemia-resistant CA3 and dentate gyrus
      neurons destined to survive suggests marked synaptic reorganization processes
      despite maintained structural integrity. More importantly, upregulation of
      binding to inhibitory GABA(A) receptors in the hippocampus indicates a relative
      shift between inhibitory and excitatory neurotransmission that we suggest may
      participate in endogenous postischemic neuroprotection.

PMID- 12053015
TI  - Calcium modulation of adherens and tight junction function: a potential mechanism
      for blood-brain barrier disruption after stroke.
AB  - BACKGROUND: This review deals with the role of calcium in endothelial cell
      junctions of the blood-brain barrier (BBB). Calcium is critical for adherens
      junction function, but it appears that calcium is also important in regulating
      tight junction function necessary for the barrier characteristics of cerebral
      microvessels. SUMMARY OF REVIEW: The BBB is critical for brain homeostasis and is
      located at the cerebral microvessel endothelial cells. These endothelial cells
      maintain their barrier characteristics via cell-cell contacts made up of adherens
      and tight junctions. Adherens junctions are calcium dependent; recent evidence
      suggests that calcium also affects tight junctions. After stroke, there is a
      disruption of the BBB. Interfering with calcium flux under hypoxic conditions can
      prevent BBB breakdown. Calcium may alter BBB junction integrity by a number of
      different signal transduction cascades, as well as via direct interaction of
      calcium ions with junction proteins. It remains to be determined whether clinical
      use of calcium channel antagonists is a viable means to reduce BBB disruption
      after stroke. CONCLUSIONS: With the widespread use of calcium channel blockers as
      clinical treatments for hypertension, which is a risk factor for stroke, the
      exact role of calcium in modulating BBB integrity needs to be elucidated.

PMID- 12053016
TI  - Biochemical basis of angioedema associated with recombinant tissue plasminogen
      activator treatment: an in vitro experimental approach.
AB  - BACKGROUND: Angioedema has been reported during recombinant tissue plasminogen
      activator (rtPA) treatment of acute ischemic stroke, often with concomitant use
      of angiotensin I-converting enzyme inhibitor treatment. Angioedema has been
      partly attributed to the nonapeptide bradykinin (BK), although its precise role
      has been poorly documented until now. The purposes of this report are 2-fold.
      First, we sought to define and characterize the in vitro kinin-forming capacity
      of rtPA when incubated with human plasma at a concentration within the
      therapeutic concentration range of rtPA attained in blood in vivo during
      fibrinolysis. Second, we sought to define the mechanism by which rtPA liberates
      BK from purified human single-chain high-molecular-weight kininogen, a key
      constituent of the contact system of plasma and the precursor of BK. SUMMARY OF
      REPORT: When incubated with human plasma, in the presence of an angiotensin I
      converting enzyme inhibitor, rtPA generates BK, which is further metabolized to
      des-Arg9-BK. The quantity of kinins generated by rtPA is similar to that observed
      during the activation of the contact system of plasma with a negatively charged
      surface, suggesting that it is physiologically relevant. The total amount of des
      Arg9-BK liberated during the incubation period depends on the aminopeptidase P
      activity, its main degrading peptidase. Additionally, incubations using purified
      proteins of the fibrinolytic and the contact system pathways show that the rtPA
      kinin-forming capacity is mediated by plasmin. CONCLUSIONS: We conclude that rtPA
      used in vitro at a therapeutic concentration has the capacity to generate
      significant quantities of kinins from human plasma. This kinin-forming activity
      depends on the activation of the fibrinolytic pathway. These data suggest that
      angioedema associated with rtPA treatment of ischemic stroke results directly
      from plasmin-mediated release of BK.

PMID- 12053017
TI  - New considerations in analyzing stroke and heart disease mortality trends: the
      Year 2000 Age Standard and the International Statistical Classification of
      Diseases and Related Health Problems, 10th Revision.
AB  - BACKGROUND: Monitoring of trends and patterns of stroke mortality will be of
      utmost importance in the coming decade. Two innovations in vital statistics may
      complicate this task and must be brought to the attention of both researchers and
      readers of research reports: the new Year 2000 Age Standard and the International
      Statistical Classification of Diseases and Related Health Problems, 10th Revision
      (ICD-10). SUMMARY OF REVIEW: For cerebrovascular diseases, the age-adjusted death
      rate is 2.4 times higher with the use of the year 2000 standard than with the use
      of the old 1940 standard. However, if rates for all years are computed with the
      use of the same age standard, the percent change from 1979 to 1995 is similar
      according to the 1940 standard (-35.8%) or the year 2000 standard (-34.3%).
      Another important effect of the change to the year 2000 standard is to reduce
      black/white differentials in age-adjusted death rates. Major discontinuities are
      not observed for mortality trends in cerebrovascular disease or heart disease
      between International Classification of Diseases, Ninth Revision (ICD-9) (1979
      1998) and ICD-10 (1999 and following years) classifications. CONCLUSIONS: All
      data users must exercise caution to specify the age standard used when assessing
      or presenting age-adjusted rates over time or between groups. The comparability
      of ICD codes chosen for years before 1999 versus 1999 or following years must be
      checked to distinguish changes due to coding from true changes in mortality
      levels.

PMID- 12053018
TI  - Warfarin-Aspirin Recurrent Stroke Study (WARSS) trial: is warfarin really a
      reasonable therapeutic alternative to aspirin for preventing recurrent
      noncardioembolic ischemic stroke?

PMID- 12053019
TI  - Evaluation of prognostic factors in radical prostatectomy specimens with cancer.
AB  - Prostate cancer (PCa) is a leading cause of morbidity and mortality in males
      accounting for approximately 30% of all new cases of cancer and approximately 14%
      of cancer deaths. Despite considerable advances achieved in the ability to detect
      and treat PCa, there have not been significant corresponding decreases in PCa
      related morbidity and mortality. Proper examination of radical prostatectomy
      specimens by the pathologists is critical in determining the need for adjuvant
      treatment and prediction of patient outcome. The goal is to tailor the
      therapeutic approach to the clinical, morphological and molecular features of
      each patient.

PMID- 12053020
TI  - Delayed high-dose intravesical epirubicin therapy of superficial bladder cancer.
      A way to reduce the side effects and increase the efficacy--a phase 2 trial.
AB  - INTRODUCTION: Intravesical epirubicin is a widely used agent for the treatment of
      superficial bladder cancer. A direct relationship between dose and activity has
      been reported: unfortunately the dose increase also increased the frequency and
      the intensity of treatment-related side effects. MATERIALS AND METHODS: A phase 2
      trial was designed to evaluate the toxicity and the activity of a delayed
      (biweekly) high-dose (80 mg) epirubicin therapy of superficial bladder cancer.
      Thirty patients with intermediate risk superficial bladder cancer (stage mTa, G2)
      have been treated with transurethral resection and epirubicin intravesical
      therapy: the patients were given 80 mg epirubicin in 50 ml sterile saline every 2
      weeks for 6 times (delayed regimen). The follow-up ranged from 3 to 26 months.
      Eleven of 30 (37%) patients experienced a local adverse reaction to intravesical
      epirubicin requiring specific medication (grade > or = 2 according to NCI-CTC
      v.2.0, 1999). No systemic toxicity related to the treatment was observed.
      RESULTS: Out of the 29 evaluable patients, 22 (76%) were free of disease after
      the induction course, 6 (21%) had superficial bladder cancer recurrences and 1
      (3%) experienced tumor progression. CONCLUSION: A delayed (biweekly instillation)
      high-dose (80 mg) intravesical epirubicin regimen was acceptable in terms of side
      effects and showed a worthwhile therapeutical impact in patients with
      intermediate risk superficial bladder cancer.

PMID- 12053021
TI  - Prostate-specific antigen dynamics predict risk of progression in advanced
      prostate cancer treated with bicalutamide plus castration.
AB  - OBJECTIVE: The aim of this study was to investigate the prognostic value of
      prostate-specific antigen (PSA) dynamics in patients treated with combined
      androgen blockade (CAB). METHODS: Patients with locally advanced or metastatic
      prostate cancer (n = 317) received bicalutamide (50 mg once daily) plus either
      goserelin acetate or surgical castration for 48 weeks. Cox's proportional hazard
      analysis was used to determine whether the decline of PSA following the use of
      this combination is predictive of a delay in progression. RESULTS: PSA levels at
      weeks 4 and 12 were statistically significant prognostic markers in predicting
      disease progression. The PSA rate of change to week 12 was also a statistically
      significant prognostic marker, although the PSA rate of change at week 4 did not
      reach statistical significance. These results were statistically less robust than
      those for PSA levels. Bicalutamide plus castration was well tolerated and
      effective in advanced prostate cancer. CONCLUSION: These results suggest that PSA
      dynamics at weeks 4 and 12 may predict time to progression in advanced prostate
      cancer treated with CAB.

PMID- 12053022
TI  - Significance of vitamin D receptor gene polymorphism for risk and disease
      severity of prostate cancer and benign prostatic hyperplasia in Japanese.
AB  - OBJECTIVE: Recent studies have demonstrated an association between vitamin D
      receptor (VDR) genotype and prostate cancer. Currently, there is a scarcity of
      data regarding the association of VDR genotype with benign prostatic hyperplasia
      (BPH). The purpose of this study was to investigate the TaqI VDR polymorphism in
      Japanese prostate cancer patients, Japanese BPH patients and Japanese controls in
      order to determine if an association exists between VDR genotype and the risk of
      developing prostate cancer and BPH as well as disease severity. METHODS: 110
      prostate cancer patients, 83 BPH patients and 90 male age-matched controls were
      genotyped for a previously described TaqI restriction fragment length
      polymorphism at codon 352 in exon 9 of the VDR gene. Products were digested into
      T allele or t allele according to the absence or presence of a TaqI restriction
      site with individuals being classified as TT, Tt or tt. RESULTS: The frequency of
      the genotype tt was higher in the control group (6.7%) compared to patients with
      prostate cancer (1.8%) and BPH (3.6%) but this was not statistically significant.
      However, the frequency of the genotype TT was significantly higher among prostate
      cancer patients with locally advanced or metastatic disease (T3/ T4/N1/M1)
      compared to controls (p = 0.001). In addition, the genotype TT was significantly
      higher among prostate cancer patients with a high Gleason grade of tumor (grade
      5) compared to controls (p = 0.0001). In addition, the genotype TT was
      statistically higher in BPH patients with high prostate volume (volume >50 cm(3))
      compared to controls (p = 0.001). CONCLUSION: These data demonstrate that VDR
      genotype plays an important role in determining the risk of more advanced and
      aggressive prostate cancer as well as prostatic enlargement in Japanese men.

PMID- 12053023
TI  - Predicting the extent of prostate cancer using a combination of serum prostate
      specific antigen-alpha(1)-antichymotrypsin complex and systematic biopsy.
AB  - OBJECTIVE: The objective of the present study was to evaluate the usefulness of
      the combined systematic biopsy with serum prostate-specific antigen-alpha(1)
      antichymotrypsin complex (PSA-ACT) level to predict the extent of prostate
      cancer. MATERIALS AND METHODS: Sixty-two patients with clinically organ-confined
      disease who underwent radical prostatectomy were evaluated for serum PSA and PSA
      ACT levels, systematic biopsy, and the pathological stage. RESULTS: The incidence
      of extraprostatic disease in patients with more than half the biopsy cores
      positive or > or = 8 ng/ml PSA-ACT was significantly higher than those with less
      than half positive or <8 ng/ml PSA-ACT, respectively, whereas cancer in bilateral
      lobes or > or = 10 ng/ml PSA could not be used as a predictor of extraprostatic
      disease. Furthermore, in those with more than half the biopsy cores positive and
      > or = 8 ng/ml PSA-ACT or those with more than half the biopsy cores positive and
      > or = 10 ng/ml PSA, extraprostatic disease was significantly more common than in
      those with less than half positive and <8 ng/ml PSA-ACT or those with less than
      half positive and <10 ng/ml PSA, respectively. However, the incidence of
      extraprostatic disease predicted by these three variables was not significantly
      better than those by the two variables (percentage positive biopsy cores plus
      serum PSA-ACT or PSA). CONCLUSIONS: The combined systematic biopsy with serum PSA
      ACT or PSA could be used as a useful predictor for the extent of prostate cancer.
      Patients with more than half the biopsy cores positive and > or = 8 ng/ml PSA-ACT
      or > or = 10 ng/ml PSA could avoid a prostatectomy because there is a high
      probability that they have extraprostatic disease.

PMID- 12053024
TI  - Clinical characteristics of alpha-blocker responders in men with benign prostatic
      hyperplasia.
AB  - BACKGROUND: Currently, alpha-blocker is becoming first-line drug therapy for
      benign prostatic hyperplasia (BPH). Although highly effective results are
      obtained with this therapy, a difference between the objective and subjective
      response rates is reported. To prevent unnecessary medical treatment and to
      predict the alpha-blocker response, we characterized the clinical features of
      alpha-blocker responders in men with BPH. METHODS: Twenty-two men were
      consecutively enrolled in this study and received tamsulosin 0.2 mg once daily
      for 4-6 weeks. The primary measures of efficacy were maximum urinary flow rate
      (Q(max)) determined from the flow measurements and international prostate symptom
      score (IPSS). Those with an increase in Q(max) of > or = 30% from baseline and a
      decrease in IPSS of > or = 25% from baseline were defined as Q(max) responders
      and IPSS responders, respectively. Clinical findings such as age, pretreatment
      IPSS and Q(max), serum prostate-specific antigen (PSA), total prostate volume,
      transition zone (TZ) volume, TZ index and T(2)-weighted magnetic resonance image
      (MRI) of the prostate TZ were compared between responders and non-responders for
      both criteria. RESULTS: In 17 of 22 (77.2%) patients IPSS improved by > or = 25%.
      In 9 of 22 (40.9%) patients Q(max) improved by > or = 30%. There were no
      differences in clinical findings between IPSS responders and non-responders. On
      the contrary, Q(max) responders showed smaller total prostate and TZ volumes, a
      smaller TZ index and a lower intensity of the TZ in MRI than Q(max) non
      responders. CONCLUSIONS: Determination of the prostate volume and MRI findings of
      the inner prostate gland were useful in predicting Q(max) responders to the alpha
      blocker in men with BPH. In contrast, there were no clinical characteristics of
      the IPSS responders. IPSS responders without a Q(max) response should be closely
      followed while continuing the alpha-blocker therapy for a long duration.

PMID- 12053025
TI  - Relationship between the shape of passive urethral resistance relation and
      prostatic histology in patients with benign prostatic hyperplasia.
AB  - We assessed the relationship between the type of passive urethral resistance
      relation (PURR) and prostatic histology in 28 patients with benign prostatic
      hyperplasia (BPH), who underwent transurethral resection of the prostate. PURR
      was classified into three types according to pressure-flow plots, and resected
      specimens were analyzed by quantitative morphometry. Patient age, prostatic
      volume and the area densities of each histological component did not show
      significant differences among the three groups. However, there was a trend to
      correlation between prostates with a high glandular component and urethral
      compliance. Further studies of larger populations are needed to validate this
      assumption.

PMID- 12053026
TI  - Benign prostatic hyperplasia: correlations between receptor density and binding
      affinity of alpha(1)-adrenoceptors and several clinical parameters.
AB  - The aim of the study was to determine whether relations do exist between the
      concentration and activity of alpha(1)-adrenoceptors, both inside the prostatic
      adenoma and the periurethral zone corresponding to the bladder neck, and clinical
      and biological parameters such as symptoms, evaluated by the American Urological
      Association (AUA) score, age, weight of the prostate, PSA, and the flow rate.
      Twenty patients with symptomatic benign prostatic hyperplasia were selected for
      an open prostatectomy. One gram of tissue was dissected from inside the adenoma
      and 1 g from the periurethral zone corresponding to the bladder neck. The
      alpha(1)-adrenoceptors were evaluated for the apparent dissociation constant
      (K(d)) and the maximal number of binding sites (B(max)). A correlation seems to
      exist between receptor density inside the adenoma and the bladder neck and an
      inverse correlation between receptor density and the AUA total symptoms score.
      Finally, a highly significant difference was found in patients with an AUA score
      of <15 or >15. No relationship was found between receptor binding affinity and
      the considered clinical parameters.

PMID- 12053027
TI  - Prostaglandin E(1)-based vasoactive cocktails in erectile dysfunction: how
      environmental conditions affect PGE(1) efficacy.
AB  - INTRODUCTION: The chemical stability of prostaglandin E(1) (PGE(1)) in
      physiological solution has been studied in different environmental conditions.
      However, very little data exist regarding the PGE(1) stability and the consequent
      breakdown products in PGE(1)-based vasoactive cocktails under different
      environmental conditions. OBJECTIVE: To evaluate the loss of the therapeutic
      efficacy of PGE(1) either alone or in combination with other vasoactive
      substances under different storage conditions. MATERIALS AND METHODS: Utilizing
      high performance liquid chromatography the PGE(1) content was evaluated alone and
      in association with papaverine and papaverine plus phentolamine at temperatures
      of 2-8 and at 20 degrees C, and after 15, 30, 60, 90 and 120 days of storage
      using multivariate statistical analysis of variance. RESULTS: We found that the
      time of storage significantly affects PGE(1) activity. Furthermore, both the
      storage temperature and cocktail composition had a significant effect on PGE(1)
      stability. The chromatographic studies did not disclose the presence of the
      principal degradation products of PGE(1) (PGA(1), PGB(1)). The presence of
      papaverine and temperature of 20 degrees C have the greatest effect on the
      degradation of PGE(1 )during the first 30 days of storage. DISCUSSION:
      Temperature and time are prevalent factors determining the slow and progressive
      deterioration curve of PGE(1) after 30 days of storage. None of the environmental
      conditions evaluated was so drastic to determine the presence of PGA(1) and
      PGB(1). CONCLUSION: For clinical use, one should note that PGE(1) maintains 50
      80% of its efficacy for about 1 month even if stored at room temperature (20
      degrees C) and/or combined with papaverine.

PMID- 12053029
TI  - Arteriosclerosis of penile arteries: histological findings and their significance
      in the treatment of erectile dysfunction.
AB  - OBJECTIVES: In this pathomorphological study, location, distribution, and degree
      of arteriosclerotic stenoses in penile arteries from unselected cadavers are
      investigated. The findings are discussed in the context of penile
      revascularization and may explain the poor results of this form of surgery in
      older patients with general arteriosclerosis. MATERIALS AND METHODS: 120 penile
      specimens from 120 cadavers were examined histologically after van Gieson
      staining. Transverse sections were performed at the level of the pubic bone, in
      the middle of the penis, and at the sulcus coronarius. At these levels the dorsal
      and deep penile arteries were examined. RESULTS: We found arteriosclerotic
      stenoses of the penile arteries in 65% of the specimens. Of these stenotic
      lesions, 20.4% were situated proximally, 37.1% centrally, and 42.5% distally.
      CONCLUSIONS: In patients with arteriosclerotic stenoses of the penile arteries,
      microsurgical penile revascularization to the proximal part of the dorsal
      arteries at the base of the penis seems to be without any relevant long-lasting
      hemodynamic effect, because the blood flow will be impeded by the peripheral
      stenoses. This can explain the poor results of revascularization in this group of
      patients.

PMID- 12053028
TI  - Is sildenafil citrate an alternative agent in the evaluation of penile vascular
      system with color Doppler ultrasound?
AB  - IINTRODUCION: The ideal diagnosis and therapeutic agent for erectile dysfunction
      (ED) would be an oral drug taken prior to color Doppler ultrasound (CDU)
      examination and sexual intercourse. In the present study we have investigated if
      the efficacy of oral sildenafil is optimal in the diagnosis of underlying
      pathology of ED. MATERIAL AND METHODS: The study group comprised of 41 patients
      with ED. Firstly, all patients underwent CDU examinations after the combined
      intracavernosal injection of 60 mg of papaverine and sexual stimulation (CIS).
      Secondly, these patients were examined after taking 50 mg of oral sildenafil
      citrate combined with self-manual and visual sexual stimulation. RERSULTS The
      differences of peak systolic velocity values were statistically significant
      between CIS and sildenafil (right: 40.7 +/- 2.9 vs. 28.7 +/- 3.3; left: 41.2 +/-
      3.3 vs. 25.7 +/- 2.4; p < 0.001) in patients with normal penile vascular system.
      However, end-diastolic velocity and resistance index values were not significant
      between the same groups. In addition, there were not significant differences for
      peak systolic and end-diastolic blood flow velocities and resistances index with
      CIS and sildenafil in cases with vasculogenic ED. CONCLUSIONS: Sildenafil citrate
      plus visual sexual stimulation is not reliable as CIS to make accurate
      interpretation of penile vascular status using CDU. On the other hand, in some
      cases suspected of psychogenic ED after detailed sexual history, sildenafil might
      be tried as an initial step of the functional evaluation with CDU in order to
      prevent prolonged erection risk with intracavernosal injection of vasoactive
      agents.

PMID- 12053030
TI  - Neodymium-YAG laser core through urethrotomy in obliterative posttraumatic
      urethral strictures after failed initial urethroplasty.
AB  - OBJECTIVE: To assess the feasibility, problems and results of Nd-YAG laser core
      through urethrotomy in the management of failed urethroplasty for posttraumatic
      bulbomembranous urethral strictures. MATERIAL AND METHODS: 61 patients with
      obliterative posttraumatic urethral strictures were treated by Nd-YAG laser core
      through urethrotomy between May 1997 to April 2000. Of these, 5 patients had
      failed end-to-end urethroplasty done as an initial procedure at various periods
      of time. The procedure was performed as day care and patients were discharged
      within 6 h of procedure. RESULTS: At 24-30 months of follow-up, all patients are
      voiding well and are continent. Auxiliary procedures were required in 2 cases.
      CONCLUSION: Nd-YAG laser core through urethrotomy is a feasible day care option
      for patients of obliterative urethral strictures following failed initial
      urethroplasty with successful outcome.

PMID- 12053031
TI  - The effect of diltiazem on the healing of traumatic urethral inflammation.
AB  - OBJECTIVE: To investigate the effect of diltiazem, a calcium channel blocker, on
      healing of the traumatic urethral inflammation when applied systemically or
      locally. MATERIALS AND METHODS: 21 adult male Wistar rats (230-250 g) were
      assigned to group 1 (n = 7) = control, group 2 (n = 7) = local application or
      group 3 (n = 7) = systemic application. In group 1, only a urethral injury was
      achieved at the 12-o'clock position by gently introducing and drawing a tiny hook
      in the urethra until urethral bleeding occurred. In group 2, after the same
      procedure, 10 mg/kg diltiazem was applied retrogradely via a 22-gauge Angiocath
      intraurethrally for 5 consecutive days, while the same account of the drug was
      administered intraperitoneally in group 3. After 21 days, the rats were
      sacrificed for urethrectomy. Pathologically, the thickness of connective tissue,
      the regularity of the epithelial lining, the presence of the inflammation and the
      density of collagen were evaluated with Masson's trichrome staining. The Mann
      Whitney U test was used for statistical analyses. RESULTS: The mean connective
      tissue thickness was 0.77 +/- 0.39, 1.01 +/- 0.77 and 0.93 +/- 0.53 microm in
      groups 1, 2 and 3, respectively. The differences between the groups were
      insignificant (p > 0.05). The hyperplastic epithelial lining in the study groups,
      with both systemic and local applications, was markedly infrequent and the
      inflammation was less prominent. However, these differences did not reach
      statistical significance. CONCLUSIONS: Diltiazem appears not to have any
      preventive effect on connective tissue formation when applied locally or
      systemically in our urethral injury model.

PMID- 12053032
TI  - Habitual intake of lactic acid bacteria and risk reduction of bladder cancer.
AB  - INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota,
      shows antitumor activity in experimental animals. One clinical trial using L.
      casei showed a significant decrease in the recurrence of superficial bladder
      cancer. So, to assess the preventive effect of the intake of L. casei, widely
      taken as fermented milk products in Japan, against bladder cancer, we conducted a
      case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10)
      were selected from 7 hospitals, and 445 population-based controls matched by
      gender and age were also selected. Interviewers asked them 81 items. The
      conditional logistic regression was used to estimate adjusted odds ratios (OR).
      RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those
      of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27
      0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week,
      respectively. CONCLUSION: It was strongly suggested that the habitual intake of
      lactic acid bacteria reduces the risk of bladder cancer.

PMID- 12053033
TI  - Influence of urinary sialic acid on calcium oxalate crystal formation.
AB  - Using seed crystal method, whole-urine method, and scanning electron microscopy,
      the inhibitory effects of sialic acid and osteopontin (OPN) on aggregation/growth
      of CaOx crystals were investigated. Using the seed crystal method, sialic acid
      showed an inhibitory effect on CaOx crystal aggregation/growth in a concentration
      dependent manner, but almost no effect was observed using the whole-urine method.
      OPN showed an inhibitory effect on aggregation/growth in both experimental
      systems. The inhibitory effect of asialo-OPN on aggregation/growth was
      approximately 20% lower than that of OPN in the experiment using the seed crystal
      method and approximately 15% lower in the experiment using the whole-urine
      method. Scanning electron microscopy showed that OPN and sialic acid inhibit the
      aggregation of CaOx crystals. The above findings show that sialic acid accounts
      for about 15-20% of the involvement of OPN in CaOx crystallization.

PMID- 12053034
TI  - Analysis of the trace element contents of inner nucleus and outer crust parts of
      urinary calculi.
AB  - In this study, the lead, cadmium, nickel, and aluminum concentrations were
      analyzed in inner nucleus and outer crust parts of various kinds of urinary
      calculi, and the results obtained were statistically compared. Significant
      differences were found among the element concentrations in the different stone
      groups. In general, higher element concentrations were found in the nuclei as
      compared with the crust parts. In addition, some significant intra- and
      intercorrelations were established among the elements analyzed. The results
      suggest that some trace elements, including lead, cadmium, nickel, and aluminum,
      together with other factors may have as yet no clarified functions in the stone
      precipitation process in the urinary tract.

PMID- 12053035
TI  - Squamous cell carcinoma in long-standing untreated lichen sclerosus et atrophicus
      of the penis.
AB  - Lichen sclerosus et atrophicus is an uncommon disease of skin and genital mucosa
      in both sexes. Involvement of the male genital mucosa is usually complicated by
      recurrent balanoposthitis, ulceration, phimosis, and meatal stenosis. The
      development of a squamous cell carcinoma is extremely rare in genital lichen
      sclerosus et atrophicus in males as compared with females. We report a 70-year
      old male with a squamous cell carcinoma of the glans superimposed on long
      standing lichen sclerosus et atrophicus of glans and prepuce. The patient in
      addition had a basal cell carcinoma on his face. Awareness of this rare
      complication of lichen sclerosus et atrophicus in males is emphasized.

PMID- 12053036
TI  - Solitary contralateral adrenal metastasis after nephrectomy for renal cell
      carcinoma.
AB  - Malignant involvement of the contralateral adrenal gland in cases of renal cell
      carcinoma is extremely rare. Solitary metachronous metastatic involvement of the
      contralateral adrenal gland from renal cell carcinoma is rarely diagnosed during
      life. In fact, clinical signs and symptoms of adrenal insufficiency are rare in
      these patients. We report a case of renal cell carcinoma with solitary
      metachronous contralateral adrenal metastasis occurring 9 years after radical
      nephrectomy.

PMID- 12053037
TI  - Pheochromocytoma and multifocal functioning paraganglioma in a 9-year-old boy
      with von Hippel-Lindau disease.
AB  - We report the case of a 9-year-old boy presenting with multifocal paraganglioma
      partially involving the right suprarenal gland, abdominal paraganglia, and the
      left para-aortal retropleural region. Von Hippel-Lindau disease (VHL) was
      diagnosed exclusively by VHL-gene analysis. Other clinical signs of VHL were
      lacking. After a complaint-free period of 7 months the boy developed a
      metachronous paraganglioma adjacent to the opposite adrenal gland. Patients with
      VHL disease should undergo adrenal-sparing surgery.

PMID- 12053038
TI  - Successful surgical reconstruction of ruptured renal pelvis following blunt
      abdominal trauma.
AB  - A 25-year-old man with occult ureteropelvic obstruction presented with abdominal
      pain 3 h following blunt abdominal trauma. Isolated rupture of the right renal
      pelvis was promptly diagnosed and the patient underwent immediate pyeloplasty
      according to the Anderson-Hynes procedure. The patient made an uneventful
      recovery. One year after surgery, renal function was satisfactory.

PMID- 12053039
TI  - Dorsal bony septum: a split cord malformation variant.
AB  - Split cord malformations (SCMs) are rare spinal anomalies and their
      classification is still a matter of debate. There is no widespread consensus on
      the embryological basis of this entity. The unified theory, proposed by Pang et
      al. [Neurosurgery 1992;31:451-480], was an attempt to explain the embryogenetic
      mechanism as a basic error occurring around the time when the primitive
      neuroenteric canal closes. We report two unusual cases of SCMs with a dorsally
      situated bony spur. We analyzed the radiological, clinical and surgical features
      of the lesions and were not able to classify these cases according to the unified
      theory. Further embryological studies should be conducted to elucidate the
      mechanisms of occurrence of these lesions, and the dorsal bony septum variant
      should be considered in SCM surgery.

PMID- 12053040
TI  - Experimental split cord malformations.
AB  - OBJECTIVE: To induce experimental split cord malformations (SCMs) produced
      through the surgical induction of a dorsal midline fistula. METHODS: In addition,
      the theory of embryogenesis of SCMs was verified by examining the developmental
      process of this experimentally induced anomaly. In Cynopus pyrrhogaster
      (amphibian) embryos (stage 18), the neural plate and notochord were split
      regionally to construct a fistula that appeared to be the ectopic neurenteric
      canal. Following this procedure, the embryonic development was traced
      morphologically and histologically. RESULTS: Following the incubation and
      breeding period, split cord malformation was observed in some animals. Scoliosis,
      spina bifida, vertebral anomaly and subcutaneous manifestations were also
      observed with SCMs. CONCLUSIONS: The observations made in these experimentally
      induced SCMs are consistent with the findings in human SCMs. We report an
      experimental animal model of split cord malformation, in which double spinal
      cords were developed in the spinal canal. In addition, we examined the
      embryogenesis of SCMs. This study indicates that SCMs may arise through a process
      of dorsal midline fistula of the neural plate.

PMID- 12053041
TI  - Ninth cranial nerve stimulation for epilepsy control. Part 1: efficacy in an
      animal model.
AB  - OBJECTIVE: To characterize the effects of stimulation of the nerve of Hering (HN;
      cranial nerve nine) in controlling seizure activity using a canine model.
      METHODS: Using penicillin applied topically to a region of the cerebral cortex,
      16 seizure-type continuous epileptiform discharges were generated. Ten specimens
      of HN (five left-sided and five right-sided) were dissected from the cervical
      region in five dogs and stimulated at varying parameters to determine the effects
      in controlling epileptiform activity. Electroencephalography (using a
      multielectrode array), electrocardiography and other vital signs were
      continuously monitored for side effects. RESULTS: Resolution of continuous
      epileptiform activity following stimulation was found in 12 of 16 trials (75%);
      no spontaneous resolution was noted in the absence of stimulation, and
      stimulation significantly shortened seizure duration (p < 0.05). Mean
      epileptiform activity duration was 139 s prior to stimulation (range 1-432 s),
      with a mean poststimulation delay of 17 s until resolution and a mean interictal
      time of 399 s. Two specimens became free of seizure activity for the duration of
      our study (p < 0.001). No significant side effects (such as the potentially life
      threatening cardiac problems seen with right-sided cervical vagal nerve
      stimulation) were found with stimulation of either left- or right-sided HN.
      Stimulation of other regional nerves (e.g. twelfth cranial nerve, nerves of the
      cervical plexus) failed to yield similar control of epileptiform activity.
      CONCLUSIONS: The results of this pilot study suggest that stimulation of the HN
      can successfully control focal seizure activity in the majority of cases. Pending
      further study, stimulation of the HN may have a role in the management of
      patients suffering from medically and otherwise surgically refractory epilepsy.

PMID- 12053042
TI  - Ninth cranial nerve stimulation for epilepsy control. Part 2: surgical
      feasibility in humans.
AB  - OBJECTIVE: To determine the anatomical and surgical feasibility of placement of a
      stimulator around the nerve of Hering (HN; a branch of cranial nerve nine). We
      previously determined the success of HN stimulation in controlling epileptiform
      activity in a canine model study. The present study assessed the ability to
      extrapolate the ease of surgical dissection and surrounding anatomy to humans.
      METHODS: Fifteen human cadavers (8 male, 7 female) were studied. The HN on each
      side was specifically evaluated in each specimen with respect to its presence,
      size, surgically accessible length below the mandibular angle, relationship to
      the internal carotid artery (ICA) and carotid bifurcation and relation to the
      common facial vein (CFV), thyroid cartilage (superior edge) and superior cervical
      ganglion (SCG). RESULTS: All 15 cadavers exhibited specimens of HN bilaterally,
      with the nerve diameter ranging from 0.5 to 1.5 mm (mean 1.0 mm); in relation to
      the ICA, the HN coursed anteromedially in 60%, anteriorly in 33% and
      anterolaterally in 7% of cases, and appeared to distinctly emerge at the level of
      the carotid bifurcation in all specimens. The surgically accessible length below
      the mandibular angle ranged from 6 to 30 mm (mean 15 mm). Relative to the carotid
      bifurcation, the superior edge of the thyroid cartilage was -35 to 33 mm (mean 
      5.4 mm) above; the CFV, which was clearly identifiable in only two thirds of the
      specimens, was -10 to 15 mm (mean 3.0 mm) above; and the inferiormost portion of
      the SCG was 6-30 mm (mean 16.6 mm) above. CONCLUSION: This study indicates that
      the HN was clearly present and surgically accessible in all human specimens.
      Based on the present study and our previous canine study, HN stimulation could be
      an important therapy for medically intractable epilepsy.

PMID- 12053043
TI  - Cerebrospinal fluid shunt survival and etiology of failures: a seven-year
      institutional experience.
AB  - BACKGROUND: Innovations in shunt technology and neuroendoscopy have been
      increasingly applied to shunt management. However, the relative life span of
      shunts and the etiology of shunt failure have not been characterized recently.
      METHODS: We reviewed the records of all shunting procedures at our institution
      between January 1992 and December 1998. Independent predictors of shunt failure
      were analyzed via multivariate Cox regression analysis in 836 shunting
      procedures. Independent predictors of the etiology of failure (infection,
      proximal obstruction, distal malfunction) were analyzed via multivariate logistic
      regression analysis in the 383 shunts which failed. RESULTS: A total of 353
      pediatric patients underwent 308 shunt placements and 528 revisions. The risk
      (hazard ratio; HR) of shunt failure decreased as a function of time in both
      primary placements and revised shunts. In failed shunts, the odds of infection
      decreased 4-fold per year of shunt function, while the odds of distal malfunction
      increased 1.45-fold per year. Increasing number of shunt revisions (HR 1.31, p <
      0.05), decreasing patient age in years (HR 1.04, p < 0.001), gestational age <40
      weeks (HR 2.15, p < 0.001) but not the etiology of hydrocephalus were associated
      with an increased risk of shunt failure. Revisions versus primary placements,
      Dandy-Walker cysts and gestational age <40 weeks were independently associated
      with proximal, distal and infectious causes of failure, respectively.
      CONCLUSIONS: The long-term shunt revision rates observed here are similar to
      those reported over the past 2 decades. Shunt life span remains poorer in shunt
      revisions and in younger patients. Patient characteristics may suggest a specific
      risk and mechanism of failure, aiding in the long-term management of shunted
      hydrocephalus.

PMID- 12053044
TI  - Duration of antibiotic therapy for the treatment of shunt infection: a surgeon
      and patient survey.
AB  - The ideal duration of antibiotic treatment for shunt infection remains a major
      unanswered question in pediatric neurosurgery. To date, no study has objectively
      determined the best length of treatment, i.e. that which minimizes both the
      length of hospital stay and the chance of reinfection. This study was undertaken
      to determine whether an increase in reinfection risk would be tolerated if the
      duration of therapy were shortened. Sixty-one members of the American Society of
      Pediatric Neurosurgeons (44 responding) and 831 patients or parents of patients
      with shunts (385 responding) were surveyed using similar questionnaires. Sixty
      four percent of neurosurgeons (28/44) and 54% of patients (178/325) responding to
      the survey would tolerate an increased reinfection risk in order to gain a
      shorter duration of treatment. These data support the feasibility of a planned
      randomized study to determine the ideal length of antibiotic treatment for shunt
      infection.

PMID- 12053045
TI  - Oncocytic paraganglioma of the cauda equina in a child. Case report and review of
      the literature.
AB  - The authors report a case of oncocytic paraganglioma of the cauda equina in a 12
      year-old girl who presented with lower back and leg pain on the right side of 6
      months' duration. Magnetic resonance imaging revealed an ellipsoidal, intradural,
      extramedullary mass causing cord compression at the level of L1. Total
      laminectomy was performed on T12 and L1, and the tumor was excised completely
      without difficulty despite adherence of the tumor to the spinal cord.
      Postoperatively, the leg pain and motor weakness were much improved. The use of
      electron microscopy, and the immunohistochemical demonstration of synaptophysin
      in this tumor, allowed a confident diagnosis of an oncocytic paraganglioma to be
      made. To the authors' knowledge, this patient represents the first definite case
      of an oncocytic paraganglioma of the cauda equina in a child.

PMID- 12053046
TI  - Papillary glioneuronal tumour in a 4-year-old.
AB  - The recently described 'papillary glioneuronal tumour' is not currently included
      in the WHO classification of tumours of the CNS. We present the youngest recorded
      case to date, and only the 3rd documented in the paediatric population. The
      incorporation of this neoplasm into the WHO classification would facilitate its
      wider recognition, providing an opportunity to elucidate its natural history and
      determine an evidence-based approach to treatment.

PMID- 12053047
TI  - Neonatal subependymal giant cell astrocytoma.
AB  - Subependymal giant cell astrocytoma (SEGCA) is a benign, slow-growing glial tumor
      that manifests with signs and symptoms of obstructive hydrocephalus most often in
      adolescent patients with tuberous sclerosis complex (TSC). Neonatal highly
      aggressive SEGCA is very rare. We report a 5-month-old child with TSC presenting
      with a cystic mass lesion in the left frontal lobe as well as multiple other
      periventricular masses. After initial conservative treatment, the child was
      readmitted with intractable seizures, a massive increase in the size of the left
      frontal lobe tumor and obstructive hydrocephalus. Despite surgical interventions,
      the child succumbed to the intracranial lesions. In this report, we discuss the
      challenges of managing SEGCA and the importance of further studies, including
      genetic studies, that may lead to a better understanding of its pathophysiology.

PMID- 12053048
TI  - Pediatric sylvian fissure meningioma.

PMID- 12053049
TI  - Fracture through the C2 synchondrosis in a young child.

PMID- 12053050
TI  - Jarcho-Levin syndrome.

PMID- 12053051
TI  - Graft immunogenicity revisited: relevance of tissue-specific immunity, brain
      death and donor pretreatment.

PMID- 12053052
TI  - Skin changes and tumours after renal transplantation.
AB  - Skin involvement in chronic renal failure is characterised by a multitude of
      different aspects. Apart from the typical yellow-brown discolouration of the
      skin, most often patients complain of pruritus and xerosis cutis. A marked
      actinic elastosis is noticed. Dialysis treatment alters and partly aggravates
      these pre-existing skin conditions. When chronic renal failure leads to a kidney
      transplantation, some of the reversible skin pathology, e.g. pruritus, xeroderma,
      tends to ameliorate, but a high tendency to develop malignancies becomes
      prominent.

PMID- 12053053
TI  - Effect of a prostacyclin analogue, iloprost, on urinary aquaporin-2 excretion in
      humans.
AB  - The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting
      duct depends mainly on the action of vasopressin (AVP). Recently, however, other
      regulatory factors have been identified: atrial natriuretic factor, oxytocin and
      prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 +/- 3
      years) we therefore evaluated the effect of a stable analogue of prostacyclin-2
      (PGI(2)), iloprost, on renal function and on the urinary excretion of AQP2 (U
      AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 +/- 0.15 to 1.8
      +/- 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased
      from 1.4 +/- 0.2 to 1.8 +/- 4 (p < 0.01). No significant change was found in the
      AVP serum concentration, with a basal value of 3.17 +/- 0.12 vs. 3.15 +/- 0.12
      pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study
      levels after a recovery period of 6 h. In conclusion, the PGI(2) analogue,
      iloprost, can induce U-AQP2 excretion independent of AVP.

PMID- 12053054
TI  - Hospitalizations for bacterial endocarditis after initiation of chronic dialysis
      in the United States.
AB  - AIMS: Bacterial endocarditis is a significant cause of morbidity and mortality
      but has not been studied in a national population of end-stage renal disease
      patients. METHODS: 327,993 dialysis patients in the United States Renal Data
      System initiated from 1 January 1992 to 30 June 1997 were analyzed in a
      historical cohort study of hospitalized bacterial endocarditis (ENDO, ICD9 Code
      421.x). Renal transplant recipients were excluded. RESULTS: Hemodialysis patients
      had an age-adjusted incidence ratio for ENDO of 17.86 (95% confidence interval,
      6.62-48.90) and peritoneal dialysis patients 10.54 (95% CI, 0.71- 158.13, not
      statistically significant) compared to the general population in 1996 (the
      National Hospital Discharge Survey). 6.1% of patients with ENDO underwent valve
      replacement surgery. In multivariate analysis, hemodialysis (vs. peritoneal
      dialysis), earlier year of dialysis, cardiac disease, and lower serum creatinine
      and albumin were associated with increased risk of ENDO. In Cox regression
      analysis, patients with ENDO had increased mortality, relative risk 1.48 (95% CI
      1.45-1.73). CONCLUSIONS: Patients on chronic dialysis were at increased risk for
      ENDO compared to the general population. The risk for peritoneal dialysis
      patients was not statistically significant, possibly due to the smaller numbers
      of patients on this modality. Hemodialysis (vs. peritoneal dialysis) and
      comorbidities were the strongest risk factors for ENDO identified.

PMID- 12053055
TI  - Stimulated salivary flow rate in chronic hemodialysis patients.
AB  - BACKGROUND: Reduced salivary flow has been reported in patients undergoing
      hemodialysis (HD) treatment. Our aim was to investigate the most important
      factors associated with stimulated salivary flow rate (ssfr) in chronic HD
      patients. METHODS: Fifty HD patients (27 F, 23 M, mean age 46. 7 +/- 13.2 years)
      were divided into two groups according to the duration of HD treatment as those
      receiving HD therapy less than or equal to (group I) or those more than (group
      II) 24 months. Fasting blood samples were obtained to determine hepatitis B and C
      serology, and biochemical and hematological parameters before a HD session. After
      prestimulation with a standard weight paraffin wax, stimulated saliva was
      collected in the HD patients and control group (23 F, 25 M, mean age 45.7 +/-
      19.1 years) and the flow rate was expressed as ml/min. RESULTS: Both HD groups
      consisted of 25 patients. There was no significant difference between the two HD
      groups other than serum alkaline phosphatase (ALP) levels and presence of HCV.
      The ssfr was decreased than controls in both groups (0.8 +/- 0.6 and 0.7 +/- 0.4,
      respectively, vs. 1.5 +/- 0.5 ml/min) and it did not correlate with any
      parameter. Smoking had a positive effect on ssfr in all groups. CONCLUSION:
      Although the salivary flow rate decreased significantly in chronic HD patients,
      the duration of therapy displayed no effect on the salivary changes in HD
      patients, but smoking increased ssfr.

PMID- 12053056
TI  - Serum levels of soluble CD26 and CD30 in patients on hemodialysis.
AB  - BACKGROUND/AIMS: Various abnormalities of the immune system have been
      demonstrated in patients on hemodialysis (HD). We hypothesize that the imbalance
      between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells in patients
      on HD contributes to these abnormalities. Furthermore, we investigate the
      relationship between the Th1/Th2 imbalance and HD duration. METHODS: We measured
      the serum levels of soluble CD26 (sCD26) and soluble CD30 (sCD30) in 47 patients
      on HD and in 13 patients with chronic renal failure not on HD and analyzed the
      effect of HD duration on the serum levels of sCD26 and sCD30. RESULTS: The serum
      level of sCD26 in the HD group was significantly lower than that in the control
      group. On the other hand, the serum levels of sCD30 in the HD group and in the
      CRF group were significantly higher than in the control group. In the short-term
      HD group (<1 year), the serum levels of sCD26 were lower and the sCD30 levels
      higher than those in middle-term HD group (1-10 years). CONCLUSIONS: In the HD
      group, the Th1/Th2 balance may shift towards Th2 dominance. It is possible that
      this imbalance contributes to the abnormality of the immune system in HD
      patients.

PMID- 12053057
TI  - Nonselective Beta-adrenergic blockade augments fasting hyperkalemia in
      hemodialysis patients.
AB  - BACKGROUND/AIM: Fasting hyperkalemia in patients with end-stage renal failure is
      a well-documented phenomenon. Both a decreased secretion of insulin and decreased
      beta-adrenergic receptor sensitivity may take part in this effect. METHODS:
      Twelve anuric, long-term (6.4 +/- 2.7 years; mean +/- SD) hemodialysis patients
      underwent three periods of 18-hour fasting (from 6 p.m. to 12 a.m.). At the
      beginning of each fasting period a single dose of the nonselective beta-blocker,
      nadolol (80 mg), or the beta(1)-selective blocker, betaxolol (20 mg), or placebo
      were given in a random order and in blinded fashion. The wash-out period was 7
      days. RESULTS: The mean decrease in blood pressure was similar after nadolol and
      betaxolol (18 +/- 10 vs. 19 +/- 11 mm Hg) as was a decrease in heart rate (20 +/-
      3 and 19 +/- 6, respectively). Serum potassium was not different before each of
      the fasting periods. The increase in serum potassium during fasting was highly
      significant in each case. The mean increase in serum potassium was 1.2 +/- 0.4
      mmol/l after nadolol, 0.9 +/- 0.6 after betaxolol and 0.6 +/- 0.6 after placebo.
      This effect was significantly larger after nadolol than after placebo (p = 0.01),
      but this relation was not significant with respect to betaxolol (p = 0.30). Serum
      insulin as well as glucose decreased significantly and to a similar extent during
      each fasting period. Plasma aldosterone was unchanged. CONCLUSION: Nonselective
      beta-adrenergic blockade increases the hyperkalemic effect of fasting in
      hemodialysis patients.

PMID- 12053058
TI  - Carbamylated hemoglobin as a therapeutic marker in hemodialysis.
AB  - Carbamylation requires isocyanic acid derived from urea. Carbamylation of
      hemoglobin (Hb) produces carbamylated Hb (carbHb), which could serve as a marker
      of posttranslational protein modification possibly associated with such uremic
      complications as atherosclerosis. Since relative carbHb levels are determined by
      mean urea concentration and duration of exposure, they could be used to assess
      the adequacy of a patient's hemodialysis (HD) regimen. We therefore determined
      the relationship between carbHb and urea kinetics in patients with chronic renal
      failure (CRF) undergoing maintenance HD. In pre-HD determinations as well as in
      nondialyzed subjects including healthy subjects and CRF patients without
      dialysis, carbHb correlated well with blood urea nitrogen (BUN) concentrations,
      especially with BUN averaged for the preceding 1-3 months. In HD patients, carbHb
      correlated significantly with urea kinetics (time-averaged concentration of urea,
      or TAC(urea), K(t)/V and urea reduction rate). The estimated mean urea
      concentration in HD patients calculated from the relationship between carbHb and
      averaged BUN over 3 months in the nondialyzed groups was lower than TAC(urea),
      suggesting that TAC(urea) may be an overestimate. Pre-HD BUN is not a good
      nutritional index since detrimental decreases in urea elimination from the body
      can elevate pre-HD BUN independently of nutrition. We therefore devised a new
      nutritional index, BUN/carbHb, which correlated significantly with serum albumin
      as well as the normalized protein catabolic rate. These results demonstrate that
      carbHb accurately reflects uremic control and the BUN/carbHb ratio could serve as
      an index of nutritional state in HD patients.

PMID- 12053059
TI  - Dialysis-membrane-dependent reduction and adsorption of circulating hepatitis C
      virus during hemodialysis.
AB  - BACKGROUND/AIMS: Patients on chronic hemodialysis (HD) are often infected with
      hepatitis C virus (HCV), a common cause of chronic liver disease. In some cases,
      however, decreases in the serum HCV load after HD have been documented. To better
      understand this phenomenon, we investigated the effects of various types of
      dialysis membrane on virus load in the circulation in vivo and in vitro. METHODS:
      HCV RNA levels in patients' serum, filtrate and dialyzer membranes were analyzed
      semiquantitatively by reverse transcription-polymerase chain reaction (RT-PCR)
      before and after HD treatment with two to four different types of dialysis
      membrane. HCV RNA was also determined from each fraction in in vitro dialysis and
      ultrafiltration. RESULTS: In HD patients treated with a polysulfone (PS) membrane
      and a hemophan membrane, the HCV RNA titer reproducibly decreased by a factor of
      10(-1)-10(-2). In contrast, a cuprophan (CU) membrane had no detectable effect on
      HCV viremia, and HD with the AN69 membrane reduced HCV RNA levels in only a
      subset of the patients. In addition, a PS membrane, but not a CU membrane,
      reduced the level of circulating HCV in an in vitro assay. In both in vivo and in
      vitro experiments, HCV RNA was recovered from the PS membrane itself, but not
      from the ultrafiltrate. CONCLUSIONS: Membrane-dependent adsorption of HCV occurs
      during HD, causing a transient reduction in HCV in the circulation of patients.

PMID- 12053061
TI  - QT dispersion in renal transplant recipients.
AB  - An increased QT dispersion (QTd) is associated with a variety of cardiac diseases
      and predicts sudden death. Although chronic renal failure patients and patients
      on hemodialysis are shown to have an increased QTd, evidence of increased QTd in
      renal transplant patients is scarce. In this study, renal transplant patients
      were evaluated to find out if they had an increased QTd. Thirty-four renal
      transplant recipients aged 35 +/- 8 years and 34 healthy control subjects aged 34
      +/- 8 years were included in the study. The mean time after transplantation was
      51.8 +/- 40.4 (range 5-154) months. The QT interval was measured by 12-lead
      electrocardiogram, and the QTd was defined as the difference between the maximum
      and minimum QT interval. Bazett's formula was used to correct for the heart rate
      (QTc). Both QTd and QTc dispersion (QTcd) in renal transplant patients were
      compared with those of control subjects. All patients underwent transthoracic
      echocardiographic assessment and 24-hour ambulatory blood pressure monitoring.
      Renal transplant recipients had similar QTd (37 +/- 15 vs. 39 +/- 17 ms) and QTcd
      (50 +/- 18 vs. 55 +/- 20 ms) compared to control subjects. QTd and QTcd were
      similar in patients with and without left ventricular hypertrophy (QTd 37 +/- 14
      vs. 36 +/- 17 ms and QTcd 50 +/- 14 vs. 49 +/- 21 ms, respectively). No
      association was found between QTd and left ventricular mass index or blood
      pressure measurements. The QTd was not found to be increased in renal transplant
      recipients as compared with that of healthy controls in this study. Normalization
      of the QTd after renal transplantation may be through the correction of several
      factors responsible for increased QTd in uremic patients.

PMID- 12053060
TI  - Increased urinary excretion of interleukin-17 in nephrotic patients.
AB  - BACKGROUND/AIM: Interleukin (IL)-17 is a newly discovered cytokine that is
      secreted by activated memory CD4+ T cells and modulated the early stage of immune
      response. To elucidate the pathophysiology of minimal-change nephrotic syndrome
      (MCNS), we focused on IL-17, which is one of the key factors in regulating an
      inflammatory response, and thus determined the daily excretion of IL-17 in urine.
      METHODS: For this purpose, excretion levels of IL-17 were measured in the urine
      of patients with MCNS during relapse and remission using a highly sensitive
      sandwich enzyme-linked immunosorbent assay. The data obtained were compared with
      levels of daily urinary excretion of IL-17 in patients with IgA nephropathy
      (IgAN). A group of healthy subjects served as control. In both experimental
      groups urine levels of IL-17 excretion were plotted against their daily urinary
      protein excretion. RESULTS: We demonstrated increased levels of IL-17 excretion
      in the urine of patients with MCNS and IgAN as compared to the non-nephrotic and
      healthy controls. In MCNS the daily urinary IL-17 (uIL-17) excretion was
      increased and returned to baseline with remission of the nephrotic syndrome (NS).
      We also demonstrated a positive correlation between urinary protein excretion and
      daily uIL-17 excretion. CONCLUSION: Taken together, these data indicate that uIL
      17 excretion is increased during the NS, suggesting the possibility that daily
      uIL-17 excretion may reflect the disease activity of NS.

PMID- 12053062
TI  - Predominance of type-2 immune response in idiopathic membranous nephropathy.
      Cytoplasmic cytokine analysis.
AB  - BACKGROUND: The Th1/Th2 paradigm is proving increasingly useful in the
      understanding of infectious diseases and many autoimmune diseases. Th1 cells
      predominantly produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and
      are instrumental in initiating delayed-type hypersensitivity and activating
      macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL
      13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown
      that in patients with membranous nephropathy, there may be a predominance of Th2,
      because of the presence of IgG, particularly IgG4, which belongs to a subclass of
      the type-2 immune response, and complement deposits in glomeruli. In this study,
      we investigated the immunoresponse of helper T cells, i.e. Th predominance in
      patients with idiopathic membranous nephropathy. METHODS: We used flow cytometry
      to assess the levels of circulating Th cells in patients with idiopathic
      membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the
      expression of intracellular type-1 and type-2 cytokines. Because the production
      of each of these cytokines has a specific time course, we observed the cytokine
      synthesis at 3, 6, 9 and 12 h after stimulation. RESULTS: The percentages of IL
      2+/CD4+ cells from patients with idiopathic membranous nephropathy were
      significantly lower than those from normal individuals at 6, 9 and 12 h, with the
      difference becoming more significant over time. IFN-gamma+/CD4+ cells and IL
      4+/CD4+ cells were not significantly different between the two groups. In
      patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+
      cells were significantly higher than those in normal individuals at each point in
      time. CONCLUSION: Increased IL-10-producing Th cells may lead to suppression of
      delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis,
      resulting in idiopathic membranous nephropathy.

PMID- 12053063
TI  - Enhanced expression of C chemokine lymphotactin in IgA nephropathy.
AB  - Leukocyte accumulation in the kidney is observed in patients with IgA
      nephropathy. Chemokines are a large family of cytokines chemotactic for
      leukocytes and have been shown to be upregulated in renal diseases. We previously
      reported that the gene expression of lymphotactin, a sole member of C chemokine
      subfamily, is enhanced in an animal model of crescentic glomerulonephritis, but
      its expression in human renal diseases is totally unknown. In the present study,
      we investigated the expression of mRNAs of lymphotactin and some other chemokines
      in IgA nephropathy. The expression of mRNAs for three chemokines, lymphotactin,
      MCP-1, and MIP-1beta, in renal cortex was increased and the levels of
      lymphotactin and MCP-1 mRNAs were statistically higher in patients with
      glomerular crescents than in those without crescents. These levels also
      correlated with tubulointerstitial changes and urinary protein excretion.
      Glomerular levels of mRNAs for lymphotactin and MCP-1, but not MIP-1beta, were
      higher in IgA nephropathy than controls. By immunohistochemical analysis,
      lymphotactin was detected in tryptase-positive cells (putative mast cells) in the
      interstitial space. These results suggest that lymphotactin, as well as MCP-1,
      may contribute to leukocyte infiltration and disease progression in IgA
      nephropathy.

PMID- 12053064
TI  - Ultrasonic tissue characterization of the carotid artery in chronic renal failure
      patients.
AB  - The ultrasonic reflectivity of the carotid wall, measured by means of integrated
      backscatter (IBS) analysis, has recently been evaluated in patients with
      atherosclerotic diseases and it was considered to be a prognostic marker. We
      performed B-mode measurement and IBS analysis of the carotid wall in 30 chronic
      renal failure (CRF) patients (serum creatinine 548 +/- 230 micromol/l) on
      conservative treatment and free of clinical evidence of cardiovascular
      complications; 14 were normotensives (NT) and 16 were treated hypertensives (TH).
      Thirty sex- and age-matched healthy subjects served as controls. The IBS carotid
      index was significantly higher in CRF patients than in controls (31.7 +/- 3.5 vs.
      28.9 +/- 2.3 dB; p < 0.001), and no difference was observed between TH and NT CRF
      patients. The IBS index was negatively correlated with low-density lipoprotein
      cholesterol plasma levels (r = -0.46, p < 0.05), and within the group of TH CRF
      patients the IBS index was also negatively correlated with the body mass index
      and diastolic blood pressure. The carotid intima-media thickness was similar
      between uremic patients and controls. This study demonstrates an increment in
      carotid ultrasonic reflectivity in CRF patients, independent of the presence of
      overt atherosclerotic damage, and probably related to vascular remodelling linked
      to CRF. IBS analysis can be a useful tool to detect early changes in arterial
      wall structure. However, prospective studies should be planned to define its
      prognostic importance in uremic patients.

PMID- 12053065
TI  - Cystine transport activity of heterozygous rBAT mutants expressed in Xenopus
      oocytes.
AB  - The rBAT gene encodes a transport protein for cystine and dibasic amino acids. It
      is a candidate gene for type I cystinuria, a genetic disorder inherited as an
      autosomal-recessive trait. Recently, several mutations in rBAT from Japanese
      patients with cystinuria have been reported from our laboratory. Some of these
      patients were heterozygous, which appears to be inconsistent with the previous
      concept that mutations in rBAT are recessive. To investigate the function of
      heterozygous mutants, we introduced these mutations into rBAT gene and analyzed
      the transport activity of cystine associated with the mutants in Xenopus oocytes.
      Co-injection of the mutant T1037C (L346P) and the polymorphism G1854A (M6181)
      into Xenopus oocytes produced a transport activity of 67.9% of the wild type.
      Oocytes co-injected with T2017C (C673R) and wild type had a transport activity of
      70.3% of the wild type. These findings indicate that the heterozygous mutants
      show decreased transport activity compared to wild-type rBAT. Further, some
      mutants in rBAT may show decreased cystine transport activity even in
      heterozygous condition, which may contribute to stone-forming cystinuria.

PMID- 12053066
TI  - Creatinine inhibits D-amino acid oxidase.
AB  - Inhibition of D-amino acid oxidase (DAO) activity by various uremic retention
      products and guanidino compounds was investigated. Creatinine (CTN) was found to
      inhibit DAO at a similar concentration in the sera of uremic patients. The
      inhibition was competitive and the K(i) value was 2.7 mM. Moreover, CTN was shown
      to interact with flavin adenine dinucleotide (FAD), a coenzyme of DAO. The UV
      spectral change of FAD bound to DAO was observed in the visible region by
      addition of CTN. These findings suggest that the increase in serum and tissue CTN
      concentrations might be responsible, in part, for the increase in D-amino acids
      in the sera of uremic patients.

PMID- 12053067
TI  - High plasma adenine concentration in chronic renal failure and its relation to
      erythrocyte ATP.
AB  - BACKGROUND: Concentration of plasma adenine has been found to increase in chronic
      renal failure (CRF). The aim of the present study was to evaluate whether high
      plasma adenine concentration contributes to the elevated ATP in erythrocytes of
      patients with CRF. METHODS: Three groups of patients with CRF were studied: (A)
      30 patients with different degree of CRF; (B) 11 patients on hemodialysis, and
      (C) 12 patients after successful renal transplantation. Concentrations of plasma
      adenine and erythrocyte adenine nucleotides were measured in groups A, B and C.
      Furthermore, adenine incorporation into erythrocyte adenine nucleotide pool was
      measured in group A. RESULTS: A positive correlation between plasma adenine and
      creatinine concentrations was found in CRF as well as between plasma adenine and
      erythrocyte ATP. Furthermore, positive correlation was evident between the rate
      of adenine incorporation into erythrocyte adenine nucleotide pool and the
      severity of CRF. A significant reduction in both plasma adenine and erythrocyte
      ATP was observed immediately following hemodalysis, but 2 days later, high
      predialysis plasma adenine and erythrocyte ATP concentrations were restored.
      Following successful renal transplantation erythrocyte ATP and plasma adenine
      concentrations reached control values. CONCLUSION: Our results provide evidence
      that plasma adenine concentration increases in parallel to the progress of the
      disease and that it could be responsible for the increase in erythrocyte ATP of
      patients with CRF.

PMID- 12053068
TI  - Urinary albumin as an indicator of diabetic nephropathy lesions in Japanese type
      2 diabetic patients.
AB  - Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt
      nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic
      patients. We examined whether a similar situation exists in 30 Japanese type 2
      diabetic patients [21 male, age 48 +/- (SD) 8 years, known duration 11 +/- (SD) 8
      years] without definable renal disease other than diabetic nephropathy. Six
      patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9
      age-matched Japanese living-related renal transplant donors. Electron microscopic
      morphometry was performed on renal biopsy specimens and related to renal
      function. Glomerular basement membrane width and mesangial fractional volume
      [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON)
      as compared with normal controls. The Vv(Mes/glom) correlated directly with
      urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement
      membrane width overlapped among the three functional categories (NA, MA, ON) and
      normal controls. IN CONCLUSION: (1) similar to Caucasian type 2 diabetic
      patients, Japanese type 2 diabetic patients have greater heterogeneity of renal
      structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not
      a reliable indicator of underlying renal structure in Japanese type 2 diabetic
      patients.

PMID- 12053069
TI  - Biliary and total extrarenal clearance of inulin and iohexol in pigs. A source of
      error when determining gfr as body clearance.
AB  - Biliary clearance, total extrarenal clearance, body and renal clearance of inulin
      and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary
      clearance of inulin, calculated as biliary excretion divided by the plasma
      concentration, was 0.04 and 0.01 ml min(-1) 10 kg(-1) and of iohexol 0.21 and 0.1
      ml min(-1) 10 kg(-1), in normal, respectively, nephrectomized pigs (p < 0.05).
      The extrarenal clearance of inulin, calculated as body minus renal clearance, was
      2.7 and 0.7 ml min(-1) 10 kg(-1) and of iohexol 3.7 and 0.7 ml min(-1) 10 kg(-1)
      in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after
      injection of the markers their plasma concentrations were much higher in the
      nephrectomized pigs. This higher plasma concentration was not matched by an
      equally higher biliary excretion and therefore biliary clearance decreased. The
      smaller total extrarenal clearance in nephrectomized pigs, i.e. the
      overestimation of GFR when calculated as body clearance, indicates that this
      source of error decreases with decreasing renal function.

PMID- 12053070
TI  - Bradykinin induces a calcium-store- dependent calcium influx in mouse mesangial
      cells.
AB  - Bradykinin (BK) elicits extracellular-dependent [Ca2+](i) elevations in mouse
      mesangial cells (MMC) that are not blocked by verapamil, nifedipine, L
      nicardipine, NiCl(2), or LaCl(3). The aim of the present study was to evaluate
      the mechanisms involved in calcium influx induced by BK in MMC. [Ca2+](i) was
      analyzed through spectrofluorometry employing fura-2-AM, and the data were
      expressed as [Ca2+](i )obtained/[Ca2+](i )basal ratio. Heparin (IP(3), a receptor
      antagonist) almost abolished the effects of BK in MMC (1.85 +/- 0.15 vs. 1.13 +/-
      0.02, n = 4, p = 0.001). Following external and intracellular calcium store
      depletion, BK's effect was absent even after successful extracellular calcium
      replenishment. ML-7 (a myosin light chain kinase inhibitor) blocked responses to
      thapsigargin (2.62 +/- 0.13 vs. 1.11 +/- 0.04, n = 4, p < 0.001), but not those
      of BK (6.51 +/- 0.39, n = 6, vs. 5.86 +/- 1.17, n = 4, p = 0.39). On the other
      hand, genistein (a tyrosine kinase inhibitor) was able to inhibit thapsigargin
      (3.12 +/- 0.22, n = 5, vs. 1.28 +/- 0.16, n = 4, p < 0.001) as well as BK
      responses (6.46 +/- 0.66 vs. 2.89 +/- 0.61, n = 4, p < 0.05). Econazole (a P-450
      monooxygenase inhibitor) inhibited the responses to both thapsigargin (3.45 +/-
      0.16 vs. 1.03 +/- 0.03, n = 4, p < 0.001) and BK (6.49 +/- 0.83, n = 6, vs. 1.17
      +/- 0.08, n = 4, p = 0.01). Finally, responses to BK were not affected by
      indomethacin (6.69 +/- 0.66 vs. 6.57 +/- 0.87, n = 4, p = 0.916). Thus, BK
      promotes an IP(3)-sensitive store-dependent calcium influx in MMC. This
      phenomenon seems to involve tyrosine kinase and P-450 monooxygenase products in
      its transduction pathway.

PMID- 12053071
TI  - Expression of nonmuscle myosin heavy chain B (SMemb) in rat allogeneic kidney
      transplantation.
AB  - BACKGROUND/AIM: Investigators have reported that the nonmuscle myosin heavy chain
      B (SMemb) expression is enhanced in various types of glomerular diseases which
      develop into nephrosclerosis. In renal transplantation, transplant glomerulitis
      is often recognized during acute rejection. Therefore, we hypothesized that SMemb
      plays important roles in acute kidney rejection. To evaluate the role of SMemb in
      the development of kidney rejection, we examined its expression in rat kidney
      transplantation models. METHODS: We used Lewis rats as recipients and Wistar rats
      as donors. Group I: controls; group II: isograft model; group III: allograft
      model; group IV: as group III +10 mg/kg/day of ciclosporin A (CsA), and group V:
      as group III + CsA administration for 5 days postoperatively. Histopathological
      and SMemb immunohistochemical studies were completed. RESULTS: Clear enhancement
      of SMemb expression was found on day 3 in group III. In groups I, II, IV, and V,
      SMemb was faintly expressed in the glomerular cells. However, after termination
      of CsA treatment, the SMemb expression increased. The expression of SMemb was
      higher in the allograft model than in either isograft or CsA-treated models.
      CONCLUSIONS: Immunohistological investigations show that the SMemb expression was
      significant from an early stage at which histopathological reactions were hardly
      identifiable. This, therefore, could be useful for an earlier diagnosis of acute
      rejection.

PMID- 12053072
TI  - Erythropoietin is beneficial in mitomycin-induced hemolytic-uremic syndrome.
AB  - Mitomycin C is a powerful antineoplastic agent. If used at high dosage, it may
      cause a secondary form of adult hemolytic-uremic syndrome (HUS). Blood
      transfusions worsen the evolution of this peculiar form of HUS. We describe a
      patient who developed HUS after treatment with mitomycin C (total dose 144 mg/m2)
      due to a carcinoma of the ascending colon. Repeated blood transfusions were
      associated with rapidly evolving renal failure coupled with anemia and
      thrombocytopenia. Haptoglobin was undetectable. Soon after starting subcutaneous
      erythropoietin, the velocity of progression of renal failure slowed whilst no
      more blood transfusions were required and haptoglobin levels returned to normal.
      Thereafter, the patient's renal function slowly worsened and she started chronic
      hemodialysis 5 years later. Up to now, all investigations have failed to show a
      relapse of her adenocarcinoma. A possible explanation of these data is that
      erythropoietin permitted the termination of blood transfusions which both
      triggered and perpetuated the syndrome. However, we cannot exclude a primitive
      effect of erythropoietin on the endothelium or on the platelets.

PMID- 12053073
TI  - Oxidative DNA damage and tubulointerstitial injury in diabetic nephropathy.
AB  - BACKGROUND: Oxidative stress is an important pathogenetic factor in underlying
      diabetic complications. Recently, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been
      reported to serve as a new sensitive biomarker of the oxidative DNA damage in
      vivo. We studied the relationship between oxidative DNA damage and
      tubulointerstitial injury in patients with diabetic nephropathy. METHODS: Type 2
      diabetic patients (n = 25) and healthy control subjects (n = 20) were studied.
      The urine concentrations of 8-OHdG were measured by a competitive ELISA. The
      severity of the glomerular changes was graded using Gellman's criteria, and the
      severity of the tubulointerstitial lesions was determined by a semiquantitative
      estimate of the space occupied by the fibrous tissue and/or interstitial
      infiltrates. RESULTS: The urinary 8-OHdG excretion were significantly higher in
      the diabetics than in the healthy controls, and tended to increase with severity
      of the glomerular diffuse lesion, but it was not significant. The urinary 8-OHdG
      excretion significantly increased with severity of the tubulointerstitial lesion.
      CONCLUSIONS: Oxidative stress may contribute to the progression of
      tubulointerstitial injury in patients with diabetic nephropathy.

PMID- 12053074
TI  - New acetylcholinesterase inhibitor (donepezil) treatment for Alzheimer's disease
      in a chronic dialysis patient.
AB  - The new-generation acetylcholinesterase inhibitor, donepezil, is useful in the
      treatment of mild-to-moderate Alzheimer's disease. A 72-year-old male chronic
      hemodialysis patient was diagnosed as having moderate Alzheimer's disease. We
      administered donepezil at 3 mg/day orally to the patient. After 1 month's
      treatment, the patient improved to a controllable psychiatric condition and was
      discharged from the hospital. The 24-hour plasma concentration profile of
      donepezil following the 3-mg once-daily dose varied from 11.1 to 18.2 ng/ml. The
      through level of donepezil was reduced from 12.4 to 10.9 ng/ml over a 3-month
      period. We did not experience any episodes of drug toxicity or adverse effects in
      this chronic dialysis patient. Donepezil treatment might have a beneficial impact
      on patients with severe renal dysfunction.

PMID- 12053075
TI  - Migration of inferior vena cava filter into renal hilum.

PMID- 12053076
TI  - Membranous glomerulonephritis, antiphospholipid syndrome, and persistent low C3
      levels associated with meningococcal disease.
AB  - A young male patient with a recent history of meningococcemia was referred to our
      hospital in his recovery period. He had signs suggesting deep venous thrombosis
      in the legs but no other abnormalities on physical examination at admission.
      Laboratory results showed proteinuria (3.1 g/day), prolonged activated partial
      thromboplastin time (56.3 s), low level of C3c (0.19 g/l), high titers of both
      IgM (27.04 MPLU/ml) and IgG (74.88 GPLU/ml) anticardiolipin antibodies and
      recanalized thrombotic changes in the deep veins of the lower extremities on
      venography. Histopathological diagnosis of the kidney disease was membranous
      glomerulonephritis. He was started on an angiotensin-converting enzyme inhibitor
      to reduce proteinuria and an oral anticoagulant to prevent thromboembolic events.
      Since no reduction in proteinuria was observed at the 10th month of therapy, the
      angiotensin-converting enzyme inhibitor was discontinued. On his last follow-up,
      approximately 1.5 years after meningococcemia, he had no complaints and no
      abnormal findings on physical examination. While both IgM and IgG anticardiolipin
      antibody titers returned to the normal range, he still had persistent proteinuria
      and hypocomplementemia.

PMID- 12053077
TI  - Multiple metabolic abnormalities in a patient with the syndrome of inappropriate
      antidiuresis.
AB  - The syndrome of inappropriate ADH secretion (SIADH) is a common cause of
      hyponatremia. However, other metabolic abnormalities have infrequently been
      described in patients with the syndrome of inappropriate antidiuresis. Here, we
      describe a female patient with hyponatremia due to SIADH who presented with a
      cluster of metabolic abnormalities and specifically hypouricemia associated with
      uricosuria, hypokalemia caused by renal potassium wasting, hypomagnesemia with
      inappropriate magnesiuria, hypophosphatemia with renal phosphate wasting and
      inappropriate calciuria. These abnormalities could be partly due to the
      extracellular volume expansion and were corrected with the water restriction
      induced increase in serum sodium levels.

PMID- 12053078
TI  - Prevalence of TT virus in a CAPD population.
AB  - TT virus (TTV) has recently been identified in patients with post-transfusion non
      A, non-G hepatitis. It is reported to be common in patients with a variety of
      liver diseases and with history of transfusion. Its pathogenesis in chronic liver
      diseases remains unclear. In this study, we have determined the prevalence of TTV
      in a continuous ambulatory peritoneal dialysis (CAPD) population and related its
      prevalence with history of previous hemodialysis, transfusion, HCV positivity and
      serum alanine amino-transferase (ALT) levels. TTV was detected in 44% of 63 CAPD
      patients and 30% of 43 healthy controls (p = 0.15). Frequency of TTV was similar
      in previously hemodialysed and never hemodialysed (8/14, 57% vs. 20/40, 41%, p =
      0.15) and previously transfused and non-transfused (7/19, 37% vs. 15/44, 34%)
      CAPD patients. Prevalence of TTV was also similar in HCV(+) and HCV(-) patients.
      Serum ALT levels were 19 +/- 16 and 20 +/- 12 U/l in TTV(+) and TTV(-) patients,
      respectively. These results indicate that prevalence of TTV in a CAPD population
      is similar to healthy controls, and other routes of transmission in addition to
      parenteral routes might be involved in the transmission of TTV.

PMID- 12053079
TI  - Psychiatric disorders among patients undergoing hemodialysis therapy.
AB  - We examined the incidence rates of psychiatric disorders in end-stage renal
      failure patients on hemodialysis (HD) based on 4-year long-term follow-up. Among
      various psychiatric disorders, the frequency of three psychiatric disorders,
      dementia, delirium, and major depression, was relatively high. One-year incidence
      rate of whole psychiatric disorders was 10.6% (7.1% in non-aged and 13.7% in
      aged). One-year incidence rate of dementia in aged patients was 4.2% (dementia of
      the Alzheimer's disease, 0.5%; multi-infarct dementia, 3.7%). One-year incidence
      rate of multi-infarct dementia in aged HD patients was 7.4 times as large as that
      in the elderly general populations, suggesting that aged HD patients tend to
      exhibit multi-infarct dementia. The high incidence rate may be closely related to
      advanced arteriosclerosis and other medical conditions. Psychiatric management is
      required for ESRD patients with three major psychiatric disorders, dementia,
      delirium, and major depression, in particular for aged patients with multi
      infarct dementia who has received long-term HD therapy.

PMID- 12053080
TI  - Renal transplantation in patients with Fabry disease.
AB  - Anderson-Fabry disease (AFd) is a rare X-linked disorder characterized by
      deficiency of alpha-galactosidase A that leads to systemic accumulation of
      neutral glycosphingolipids, predominantly globotriaosylceramide (Gb3), in body
      fluids and visceral tissues, including the kidney. End-stage renal failure is a
      common manifestation in hemizygous males that often occurs by the third to fourth
      decade of life. Usually transplanted patients exhibit improvement in clinical
      symptoms of the disease, probably related to the production of alpha
      galactosidase A from the grafted kidney, but mainly related to the increase in
      Gb3 clearance by the functioning kidney, and increased survival of red cells due
      to the correction of the uremic status with an evident decrease in the production
      of Gb3 depending from hemolysis. Several Fabry patients with successful kidney
      graft survived for 10-15 years and died for cardiovascular complications related
      to the metabolic disease. The loss of grafted kidney is due to rejection,
      thrombosis or sepsis. An important issue considering renal transplantation in AFd
      is the recurrence of the disease in the kidney graft; however, no evidence
      regarding this possibility has occurred up to now. We report herein the
      ultrastructural study of the urinary sediment of a 35-year-old male Fabry patient
      with a severe clinical form of the disease with progression to ESRF at age 29,
      and submitted to renal transplantation at 33 years. Ultrastructural findings of
      the urinary sediment documented several cells, probably tubular epithelial cells,
      with typical accumulation of myelinic bodies resulting from intracellular storage
      of neutral glycosphingolipids. This morphological evidence arises the problem of
      the possible recurrence of AFd in the kidney graft in patients with severe
      phenotype of the metabolic disease.

PMID- 12053081
TI  - Infantile renal dysfunction associated with intrauterine exposure to ritodrine
      and magnesium sulfate.

PMID- 12053082
TI  - Rhabdomyolysis after body building exercise.

PMID- 12053083
TI  - A protective role for protein C inhibitor on graft function in renal transplant
      recipients?

PMID- 12053084
TI  - Acute spontaneous spinal epidural hematoma in a hemodialysis patient with a
      bleeding tendency.

PMID- 12053086
TI  - Differentiated thyroid carcinoma in children and adolescents. Clinical
      characteristics, treatment and outcome of 15 patients.
AB  - BACKGROUND: Thyroid carcinoma in childhood and adolescence is uncommon and
      because of the slow progression of disease the standard treatment is
      controversial. The aim of this study was to perform a retrospective analysis of
      treatment results for differentiated thyroid carcinoma in this age group treated
      in our clinic. MATERIALS AND METHODS: From August 1988 to February 2001, 15
      patients between the ages of 8 and 21 years (average 16.8) were treated for
      differentiated thyroid carcinoma at Akdeniz University Medical School Departments
      of General and Pediatric Surgery. The patients included 10 (67%) females and 5
      (33%) males. None of the patients had a previous positive history of head and
      neck irradiation. All patients, except 2, were euthyroid at the time of
      diagnosis. RESULTS: Nine of the patients underwent total thyroidectomy and in 6
      cases subtotal thyroidectomy was performed. There were multiple lymph node
      metastases in 4 (27%) patients and (various forms of) cervical lymph node
      dissections were performed in these patients. In addition, 2 children (13%)
      showed pulmonary metastasis. The incidence of surgical complications was 20% (1
      permanent, 1 transient hypoparathyroidism and 1 permanent laryngeal nerve
      injury). Histological examinations revealed the following: papillary carcinoma in
      9 (60%), follicular carcinoma in 5 (33%) patients, and Hurthle cell carcinoma in
      1 (7%) patient. Postoperative radioiodine ablation was also added to treatment in
      10 (67%) of the patients and all patients received L-thyroxine in suppressive
      doses. After a median follow-up period of 57 months (range 5-149), all patients
      are alive and disease-free. CONCLUSUION: Our observations suggest that although
      most children and adolescents with differentiated thyroid carcinoma are seen with
      more extensive disease than adults, a total or subtotal thyroidectomy with an
      appropriate lymph node dissection followed by ablative radioiodine treatment
      carries a more favorable prognosis.

PMID- 12053085
TI  - The aromatase cytochrome P-450 and its clinical impact.
AB  - Cytochrome P-450 aromatase (P450arom), the key enzyme for estrogen biosynthesis,
      is encoded by a single gene, namely the CYP19 gene, localized on 15q21.2. The
      human CYP19 gene spans about 123 kb with a coding region of 9 exons (about 30 kb,
      exon II-exon X). Although there are a number of alternative first exons and nine
      different transcriptional start sides with individual promoters that permit
      tissue-specific regulation of expression, the protein expressed in these various
      tissue sites (placenta, adipose tissue, brain, bone, ovary, etc.) is the same
      regardless of the promoter used. P450arom catalyzes the conversion of
      testosterone to estradiol, of androstenedione to estrone, and of 16alpha
      hydroxylated dehydroepiandrosterone to estriol. As not only androgens but also
      estrogens are of importance, particularly in the male pubertal development,
      including bone changes which were classically considered mostly androgen
      dependent, the features of the aromatase deficiency syndrome in affected boys and
      girls as well as adult males and females are discussed. There is growing
      awareness that androgens and estrogens have general metabolic roles that reach
      far beyond reproductive processes. For instance, estrogen has a significant
      impact on carbohydrate and lipid metabolism, vascular function, and
      arteriosclerosis. In addition, extragonadal estrogen biosynthesis plays an
      important but often underestimated physiological and pathophysiological role, for
      example in breast cancer and endometriosis. Based on that knowledge, progress has
      been made as far as treatment and follow-up of these disorders are concerned. In
      addition, there is a focus on the treatment of children suffering from a lack of
      P450arom activity.

PMID- 12053088
TI  - Dehydroepiandrosterone sulfate and growth axis hormones in patients with ischemic
      heart disease.
AB  - BACKGROUND: The present study aimed to determine whether decreases in
      dehydroepiandrosterone sulfate (DHEA-S) and growth axis components precede
      cardiovascular disease or are a consequence of it. METHODS: We measured the
      concentrations in serum of DHEA-S, ACTH, cortisol, growth hormone, insulin-like
      growth factor-1 and insulin-like growth factor-binding protein-3 in 30 male
      controls and also in 37 male patients on days 0, 2, 5, 7 and 9 after suffering a
      myocardial infarction (MI). RESULTS: There was no significant variation in any of
      these parameters between the controls and the patients on day 0. However, we
      found a significant (p < 0.001) reduction in the DHEA-S concentrations of the
      patients between day 0 and subsequent days (days 2, 5, 7 and 9). CONCLUSION: We
      conclude that the decrease in DHEA-S in patients with MI is a consequence and not
      a cause of the disease.

PMID- 12053087
TI  - Growth failure in early life: an important manifestation of Turner syndrome.
AB  - The goals of this study were to test the hypothesis that girls with Turner
      syndrome (TS) experience growth failure early in life and to establish model
      based normative growth charts for 0- to 8-year-old American girls with TS. Full
      term girls with TS who had 5 or more measurements of height obtained during their
      first 10 years of life prior to initiation of growth hormone, estrogen and/or
      androgen therapy were eligible for this study. A nonlinear mixed-effects model
      comprising the first two components of the infancy-childhood-puberty (ICP) model
      of growth was fitted to the longitudinal height measurements and compared with
      those of healthy American girls. Height measurements (n = 1,146) from 112 girls
      with TS (45,X: 57.1%; 45,X/46,XX: 12.5%; 46,X, iso(X): 4.5%, and other: 25.9%)
      were analyzed. Mean height SDS fell from -0.68 at birth to -1.60 at 1 year, -1.80
      at 2 years and -1.95 at 3 years. When compared to controls (676 girls, 4,537
      measurements), girls with TS grew more slowly due to three principal factors: a
      slow growth rate of the infancy component, a slow growth rate at the onset of the
      childhood component, and delayed onset of the childhood component. Traditional
      concepts of growth failure in TS should be revised. Physicians should consider
      the diagnosis of TS in any girl with unexplained failure to thrive or short
      stature, even in the first 3 years of life.

PMID- 12053089
TI  - A cross-sectional study on biochemical parameters of bone turnover and vitamin d
      metabolites in healthy dutch children and young adults.
AB  - AIM: To provide reference data of biochemical markers of bone turnover and
      vitamin D metabolites for children and young adults. METHODS: Blood samples were
      taken from 176 healthy Dutch children and young adults (age range 7.6-25.3 years)
      to assess serum calcium, alkaline phosphatase, inorganic phosphate, osteocalcin,
      collagen type I cross-linked N-telopeptide, N-terminal propeptide of type I
      procollagen, 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 levels. Cross
      linked telopeptide of type I collagen and carboxy-terminal propeptide of type I
      procollagen were assessed in 286 subjects (age range 1.4-25.3 years). RESULTS:
      Calcium and vitamin D levels were independent of age. The peak concentrations for
      collagen type I cross-linked N-telopeptide, cross-linked telopeptide of type I
      collagen, carboxy-terminal propeptide of type I procollagen, N-terminal
      propeptide of type I procollagen, alkaline phosphatase, and osteocalcin were
      found during puberty, in girls approximately 2.5 years earlier than in boys.
      Strong correlations were found between the markers of bone turnover, while no
      correlation was found between the markers of bone turnover and bone mineral
      density measured by dual-energy X-ray absorptiometry. CONCLUSIONS: Single
      measurements of bone markers cannot predict bone density. Reference data
      according to gender, age, and Tanner stage are given which allow calculating
      standard deviation scores adjusted for age and gender.

PMID- 12053090
TI  - Ultrasonographic assessment of bone maturity in newborns.
AB  - BACKGROUND: Traditionally, the bone maturity at birth has been estimated from the
      radiological presence and size of the ossified distal femoral epiphysis. This
      study was conducted in a search for a sonographic tool for the evaluation of
      neonatal bone maturity. METHODS: We examined sonographically 256 neonates within
      24 h of birth. Gestational ages ranged from 36 to 42 weeks (mean: 39.4; median:
      40). Birth weights ranged from 1,945 to 5,000 g (mean: 3,175; median: 3,180). The
      distal femoral epiphysis was imaged on the coronal plane sonogram of the distal
      femur with the knee at 90 degrees flexion and the distal femoral epiphysis
      maximal height was recorded. The acetabulum was imaged using Graf's method in the
      coronal plane image and the acetabular diameter recorded. RESULTS: It was found
      that plotting the distal femoral epiphysis against neonatal birth weight and
      gestational age provided a simple method for assessing the bone maturity.
      According to our study, a neonate can be regarded as bone maturity percentile X
      when plotting distal femoral epiphysis height or acetabulum diameter against
      birth weight and gestational age or when averaging the four readings.
      CONCLUSIONS: We suggest performing sonography of the distal femoral epiphysis as
      a bedside tool for the assessment of skeletal maturity in newborns.

PMID- 12053091
TI  - Effects of tamoxifen on lipid profile and coagulation parameters in male patients
      with pubertal gynecomastia.
AB  - BACKGROUND/AIM: The estrogenic actions of tamoxifen on lipid profiles and
      hemostasis have been extensively demonstrated in women. Due to limited experience
      with this drug in males, it is uncertain whether these effects are also present
      in men. The aim of our study was to assess the response of blood lipids,
      lipoproteins, and coagulation parameters in a group of men taking tamoxifen.
      METHODS: We studied 15 healthy boys with pubertal gynecomastia who were given 10
      mg tamoxifen per day. Total testosterone, sex-hormone-binding globulin,
      estradiol, serum lipids, apolipoprotein B, apolipoprotein A-I, lipoprotein(a),
      fibrinogen, antithrombin III, von Willebrand factor, and markers of activated
      coagulation and fibrinolysis were determined at baseline and 1 and 3 months after
      beginning of the tamoxifen treatment. RESULTS: Total cholesterol and
      lipoprotein(a) showed moderate but significant decreases from baseline. Low
      density lipoprotein and high-density lipoprotein cholesterol concentrations as
      well as triglyceride and apolipoprotein B levels became lower, but these changes
      were not statistically significant. Among clotting parameters, antithrombin III
      was reduced, and von Willebrand factor increased significantly. Markers of
      activated coagulation and fibrinolysis remained unchanged throughout the period
      of therapy. CONCLUSIONS: The effects of tamoxifen on blood lipids and hemostasis
      we found in this group of healthy young men were qualitatively similar, but
      lesser than those previously described in women.

PMID- 12053092
TI  - Coexistence of 21-hydroxylase and 11 beta-hydroxylase deficiency in adrenal
      incidentalomas and in subclinical Cushing's syndrome.
AB  - OBJECTIVE: The prevalence of steroid secretion abnormalities was studied by
      evaluating the 17-hydroxyprogesterone (17-OHP) and 11-deoxycortisol (S) responses
      to adrenocorticotropic hormone (ACTH) stimulation in 48 patients with
      'nonfunctioning' incidentalomas and in 10 patients with 'subclinical' Cushing's
      syndrome. METHODS: In all patients the cortisol, 17-OHP, and S levels were
      measured after ACTH test. Eight patients were reinvestigated after surgery.
      RESULTS: In patients with nonfunctioning lesions, the ACTH test induced 17-OHP
      and S peaks higher than in normals (p < 0.005). In 10 cases an augmented rise of
      17-OHP and S was observed. In patients with subclinical Cushing's syndrome, the
      17-OHP peak after ACTH was greater than in patients with nonfunctioning lesions
      and in normals (p < 0.005); the S peak was also higher than in controls (p <
      0.005). In 7 of 8 operated patients, the exaggerated 17-OHP peak was normalized.
      CONCLUSIONS: A combined impairment of different enzyme activities is frequently
      present in adrenal incidentalomas; the alteration of enzymatic pathways can also
      coexist with the presence of partial cortisol autonomy.

PMID- 12053093
TI  - Cortical-sparing laparoscopic adrenalectomy in a patient with multiple endocrine
      neoplasia type IIA.
AB  - We describe the case of a patient affected by multiple endocrine neoplasia type
      IIA with a new diagnosis of an asymptomatic right pheochromocytoma. The patient
      underwent laparoscopic adrenalectomy with adrenal sparing. The removal of the
      tumor was successful with preservation of about one third of the adrenal gland.
      At the time of the last follow-up, the patient is well with partial
      hypoadrenalism without replacement therapy. The limitations to cortical-sparing
      adrenalectomy imposed by traditional open surgery (small tumor with peripheral
      location) can be reconsidered using the laparoscopic approach. Laparoscopic
      cortical-sparing adrenalectomy should become the gold standard for treatment of
      bilateral pheochromocytoma. The advantages of this technique are its efficacy and
      its reduced invasiveness with a low rate of complications either during the
      operation or in the postoperative period. Moreover, the preservation of a portion
      of the adrenal cortex may prevent the need for a life-long steroid replacement
      therapy.

PMID- 12053094
TI  - Ectopic ACTH syndrome: discrepancy between somatostatin receptor status in vivo
      and ex vivo, and between immunostaining and gene transcription for POMC and CRH.
AB  - OBJECTIVE: To characterize somatostatin receptor status in vivo and ex vivo and
      immunoreactivity and gene transcription for proopiomelanocortin (POMC) and
      corticotropin-releasing hormone (CRH) in a case of Cushing's syndrome caused by a
      sporadic metastatic medullary thyroid carcinoma (MTC). METHODS: (111)In
      octreoscan, analysis of tumorous mRNA transcripts for somatostatin receptor
      subtypes (SSTR) as well as for POMC and CRH. RESULTS: The tissue was intensely
      positive by (111)In octreoscan but expressed only SSTR 1, 3 and 5. There was
      immunopositivity only for CRH, but gene transcription for both POMC and CRH was
      seen. CONCLUSIONS: (1) This first comparison between somatostatin receptor status
      in vivo and ex vivo in MTC shows a marked positive octreoscan despite absent SSTR
      2 expression, and (2) this is the first report of a discrepancy between
      immunostaining and gene transcription for POMC and CRH.

PMID- 12053096
TI  - Gestational diabetes mellitus and neonatal hyperthyrotropinemia.
AB  - OBJECTIVE: To determine whether gestational diabetes mellitus (GDM) is associated
      with increased incidence of neonatal hyperthyrotropinemia. STUDY DESIGN: In a
      retrospective study, maternal characteristics, infant outcome and cord blood
      thyrotropin (TSH) concentration were compared between 469 diet-treated GDM
      pregnancies diagnosed by the World Health Organization 75 g oral glucose
      tolerance test (OGTT) with 474 non-diabetic pregnancies with normal OGTT results.
      RESULTS: Hyperthyrotropinemia (TSH >16 mIU/l) was found in 7.2% of the GDM
      pregnancies and 2.1% of the controls (p < 0.001), but there was no difference in
      the birth weight or gestational age. The TSH concentration was correlated with
      the OGTT 2-hour glucose value (rho = 0.0948, p = 0.029) and Apgar score at the
      fifth minute (rho = -0.1197, p = 0.009). There was no difference in the TSH or
      free thyroxine concentrations between the hyperthyrotropinemic newborns of the
      GDM and control groups. In the GDM group, the hyperthyrotropinemic newborns had a
      higher incidence (p = 0.017) of neonatal jaundice. CONCLUSIONS: Neonatal
      hyperthyrotropinemia is more frequently found in pregnancies with GDM, and this
      could have reflected increased fetal in-utero hypoxic stress in these
      pregnancies.

PMID- 12053095
TI  - Inhibin B levels in adolescents and young adults with type 1 diabetes.
AB  - OBJECTIVE/METHODS: To assess exocrine and endocrine testicular function in
      subjects with diabetes, we evaluated serum inhibin B, gonadotrophins and
      testosterone levels in 33 male adolescent and young adult patients affected by
      type-1 diabetes (age 21.0 +/- 5 years; range 14.2-33.3), with a mean disease
      duration of 12.7 +/- 5.8 years (range 1.5-25.3) and various metabolic control
      (HbA1c 7.8 +/- 1.5%; range 5.5-13.2) and compared them with those of an age
      matched group of 36 healthy control subjects (age 19.5 +/- 4.1 years; range 13.6
      28.1). Both patients and controls had a testicular volume >or=15 ml. Inhibin B
      was measured by ELISA method. RESULTS/CONCLUSION: Diabetics and controls had
      comparable inhibin B (203 +/- 74 vs. 221 +/- 69 pg/ml, respectively) and follicle
      stimulating hormone (FSH) levels, while luteinizing hormone (LH) and testosterone
      levels were significantly higher in the diabetic group. Inhibin B was negatively
      correlated both in patients and controls with FSH, while a negative correlation
      with LH was found only in the diabetic group. We conclude that our young diabetic
      males, after a mean disease duration of 12 years and various metabolic control,
      had inhibin B and FSH levels comparable to those of normal subjects. Therefore,
      they seem to have a regular testicular function and in particular a normal
      seminiferous tubule/Sertoli cell activity despite sustained hyperglycemia.

PMID- 12053097
TI  - Maternal peripheral T-helper 1-type and T-helper 2-type immunity in
      nonpreeclamptic twin pregnancies.
AB  - The percentage of T-helper (Th)1, Th2 cells and the Th1:Th2 cell ratios in
      peripheral blood from 14 normal nonpregnant women, 23 normal pregnant women and 9
      patients with twin pregnancies without preeclampsia at 28-32 weeks' gestation
      were calculated using flow cytometry. In normal pregnant women, the percentage of
      Th1 cells and Th1:Th2 ratios were significantly lower than those in nonpregnant
      women. In twin pregnancies, the percentage of Th1 cells and the Th1:Th2 ratios
      were significantly lower than those in non-pregnancies. In twin pregnancies; in
      addition, the percentage of Th1 cells was significantly lower than that in
      singleton pregnancies. Our findings show a markedly predominant Th2 immunity in
      twin pregnancies.

PMID- 12053098
TI  - Effects of vitamin K(2) on bone of ovariectomized rats and on a rat osteoblastic
      cell line.
AB  - The effects of vitamin K(2) on bone mineral density (BMD) and bone metabolic
      markers of ovariectomized rats, and those on mRNA expression of osteocalcin and
      IL-6 on a rat osteoblastic cell line, were investigated. BMD and bone metabolic
      markers were examined in ovariectomized rats after 2 months' treatment with
      vitamin K(2), and mRNA expression of osteocalcin and IL-6 were measured in the
      cell line after 24-hour treatment with vitamin K(2). Vitamin K(2) attenuated the
      decline in BMD after ovariectomy in the rats, and suppressed serum
      deoxypyridinoline levels of the ovariectomized rats. No effect on osteocalcin and
      IL-6 mRNA expression on the cell line was observed. In conclusion, vitamin K(2)
      has a bone-protective effect on ovariectomized rats.

PMID- 12053099
TI  - Detection of the cervical gland area in threatened preterm labor using
      transvaginal sonography in the assessment of cervical maturation and the outcome
      of pregnancy.
AB  - OBJECTIVES: To detect the cervical gland area in threatened preterm labor, and to
      determine its detection rate and relationship with cervical maturation and
      outcome of pregnancy in preterm labor. METHODS: This was a mixed longitudinal and
      cross-sectional study involving 615 transvaginal scans performed to detect the
      cervical gland area and measure cervical length in 101 singleton pregnancies with
      threatened preterm labor. The patients were treated with intravenous
      administration of ritodrine chloride for regular uterine contractions at 16-35
      weeks of gestation. 260 normal singleton pregnancies served as controls.
      Simultaneously conventional digital examination was used to assess the cervical
      maturation index. The detection rates of the cervical gland area, measurements of
      cervical length by sonography, and assessment of the cervical maturation index by
      digital examination in threatened preterm labor were compared with those of
      normal singleton pregnancies. In the threatened labor group, the outcome of
      pregnancy was assessed according to the sonographic absence or presence of the
      cervical gland area. RESULTS: In the normal pregnancy group, the detection rate
      of the cervical gland area remained practically constant until the 31st week of
      pregnancy (97%), but substantially decreased thereafter (70.2% in gestational
      weeks 32-35). In the threatened preterm labor group, the detection rate of the
      cervical gland area was constantly lower (44.5%) and the cervical maturation
      index was higher (4.65 score) than in the normal pregnancy group (83.1% and 1.80
      score, respectively). The outcome of pregnancy in the threatened preterm labor
      group was poorer in the subgroup with the absence of a cervical gland area than
      in the subgroup with the presence of a cervical gland area (duration of pregnancy
      257.0 vs. 271.0 days, birth weight 2,597.2 vs. 2,990.0 g, and admission to
      delivery interval 38.8 vs. 60.8 days). Highly significant correlations were noted
      among the detection rates of a cervical gland area and cervical length, cervical
      maturation index, and outcome of pregnancy. CONCLUSIONS: This study demonstrates
      for the first time that the sonographic absence of the cervical gland area
      reflects cervical maturation and could be considered as a predictor of threatened
      preterm labor and a sign of poor outcome of pregnancy in this condition.

PMID- 12053100
TI  - The plasma homocysteine levels are increased in polycystic ovary syndrome.
AB  - Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease
      risk factors. Since hyperhomocysteinemia is associated with early
      atherosclerosis, it was postulated that the homocysteine levels are higher in
      PCOS patients than in control subjects which, therefore, may explain the
      cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects
      were studied. Endocrine assays, lipid profile, homocysteine and insulin level
      determinations, and ultrasound evaluation were performed in all subjects. We
      found significantly higher mean plasma homocysteine concentrations in patients
      with PCOS as compared with controls (10.4 +/- 4.4 vs. 7.2 +/- 1.5 ng/dl; p <
      0.003). These data show that in PCOS early atherosclerosis is not exclusively
      dependent on hyperinsulinemia and elevated lipid profile - PCOS patients are
      exposed to significantly higher homocysteine levels which might increase the
      cardiovascular disease risk.

PMID- 12053102
TI  - Q-tip test and tension-free vaginal tape in the management of female patients
      with genuine stress incontinence.
AB  - INTRODUCTION: To compare the Q-tip test before and after performance of the
      tension-free vaginal tape (TVT) procedure in women with genuine stress
      incontinence, and to determine the value of the Q-tip test in order to predict
      the outcome of TVT. METHODS: Thirty-one patients with a diagnosis of stress
      incontinence but without previous anti-incontinence surgery (group I) and 10
      patients with stress incontinence and a history of previous anti-incontinence
      surgery (group II) participated in the study. None of these patients had an
      anterior vaginal wall prolapse of greater than stage I according to the
      International Continence Society Classification and, therefore, the TVT procedure
      was the only operation performed on these patients. Urethral mobility using the Q
      tip test was assessed by the same examiner at the initial physical examination
      and at the 6-month follow-up examination. Cure was defined as no leakage of urine
      postoperatively either subjectively or objectively, while failure was defined the
      objective loss of urine during the stress test. RESULTS: The mean preoperative
      and postoperative Q-tip measurement in patients without previous operation (group
      I) was 43.5 +/- 5.84 and 33.38 +/- 4.77 degrees, respectively (mean difference
      10.12 degrees), while the cure rate was 87.1%. The mean preoperative and
      postoperative Q-tip measurement in patients with previous operation (group II)
      was 17.5 +/- 4.44, and 11.1 +/- 6.88 degrees, respectively (mean difference 6.4
      degrees), while the cure rate was 40%. CONCLUSIONS: Adequate mobility of the
      proximal urethra is associated with a high success rate of the TVT procedure.

PMID- 12053101
TI  - Sexual activity, orgasm and tampon use are associated with a decreased risk for
      endometriosis.
AB  - OBJECTIVE: The purpose of the study was to determine if sexual behaviors, orgasm,
      tampon use, and douching during menstruation modify the risk of endometriosis.
      METHODS: A case-control study was conducted. Subjects (n = 2,012) consisted of
      members of the Endometriosis Association and friends not affiliated with the
      organization who completed mailed surveys. Data were analyzed using chi(2),
      Fisher's exact test, t test, and regression analyses. RESULTS: There was no
      difference between study groups concerning douching practices. However, cases
      were less likely than controls to report sometimes or often engaging in sexual
      behaviors during menstruation (p = 0.002, OR = 1.5), and sexual behaviors during
      menstruation that included orgasm (p = 0.001, OR = 1.5). Cases were also less
      likely than controls to report using only tampons (p < 0.0001, OR = 2.6).
      CONCLUSION: Sexual activity, orgasm, and tampon use during menstruation may
      confer protection against endometriosis.

PMID- 12053103
TI  - Risk factors for spontaneous preterm birth: a Northern Italian multicenter case
      control study.
AB  - Preterm birth remains one of the most serious problems facing obstetricians. The
      aim of this study was to investigate the risk factors for spontaneous preterm
      birth in northern Italy. Nine different collaborating institutions participated
      in this multicenter case-control study. Cases were defined as women who were
      spontaneously delivered of a live singleton newborn between 20 and 37 weeks of
      gestation. One control was matched to each case by delivery date, maternal age
      and parity. Seven hundred and fifty-four cases and 754 controls were available
      for data analysis. Demographic and clinical characteristics were obtained using a
      standardized questionnaire. At the time of hospital admission, urine and cervico
      vaginal samples were collected and tested for bacterial infections and bacterial
      vaginosis, respectively. Variables found to be statistically significant in the
      univariate analysis were entered in a multivariate model to examine their
      independent effects. In order of decreasing odds ratios (ORs), the factors that
      showed a significant association with preterm delivery were: previous preterm
      birth (OR 5.7, confidence interval (CI) 2.5-12.9); second-trimester miscarriages
      (OR 4.4, CI 1.3-15.3); genital bleeding before 24 weeks of gestation (OR 2.5, CI
      1.6-3.8); bacterial vaginosis (OR 2.0, CI 1.3-3.1), and previous genital
      infections (OR 1.6, CI 1.1-2.5). This study confirms that infections play a role
      in the etiology of preterm birth and that reproductive history is still the most
      important factor in identifying women at increased risk.

PMID- 12053104
TI  - Self-reported sexual symptoms in women attending menopause clinics.
AB  - The aim of the present cross-sectional study was to investigate the frequency of
      self-reported sexual symptoms in women (n = 355; age range 46-60 years) attending
      menopausal clinics in Italy and to relate them to other vasomotor, psychological,
      physical, and genital complaints. Each subject completed a visual scale for
      sexual symptoms and for other complaints frequently occurring at menopause. Pain
      during sexual intercourse (29.8%) and low libido/lack of arousal (22%) were
      significantly more frequent with age (chi(2) = 8.0, p < 0.02; chi(2) = 6.2, p <
      0.04, respectively) and years since menopause (chi(2) = 13.0, p < 0.005; chi(2) =
      11.3, p < 0.01, respectively). Reduction of sexual pleasure/satisfaction (45.9%)
      was common with age, but was more frequent with longer time since the menopause
      (chi(2) = 19.9, p < 0.001). By examining the intensity of sexual symptoms
      according to the presence of other complaints, we found that physical,
      psychological, and genital well-being significantly affects components of sexual
      response after the menopause. For example, loss of fitness, urogenital symptoms,
      a negative self-image (increase of facial hair), and depressive symptoms were
      more common in women with sexual complaints. Given the concomitant role of
      hormonal and aging determinants, a comprehensive approach to female health is
      needed when facing climacteric sexual dysfunction.

PMID- 12053105
TI  - Development of parafoveal exudates and serous retinal detachment in a pregnant
      woman with tuberous sclerosis.
AB  - The authors describe an unusual case of a serous detachment of the fovea and
      decreased vision with parafoveal exudates with subsequent spontaneous resolution
      and return of central vision in a pregnant patient with tuberous sclerosis. To
      our knowledge, this is the first report of an ocular change during gestation in a
      patient with tuberous sclerosis.

PMID- 12053106
TI  - Uterine arteriovenous malformation: ultrasonographic, magnetic resonance and
      radiological findings.
AB  - Uterine arteriovenous malformation (AVM) is a rare disease. However, it is
      important to make a rapid and precise diagnosis when it does occur, because life
      threatening massive genital bleeding may occasionally be a symptom of this
      disease. In this case report, we present a case of uterine AVM diagnosed by means
      of ultrasonographic, magnetic resonance imaging (MRI) and angiographic studies. A
      47-year-old Japanese woman was admitted complaining of severe hypermenorrhea that
      had been occurring for 5 years. Her last pregnancy was an uncomplicated term
      delivery at 32 years of age. Transvaginal and transabdominal ultrasonography
      demonstrated a thickening of the anterior wall of the uterine corpus with
      numerous cystic lesions. Color Doppler ultrasound, dynamic MRI and magnetic
      resonance angiography as well as pelvic angiography were useful for detecting the
      hypervascular lesions in this case. She was treated by a total hysterectomy and
      bilateral salpingo-oophorectomy under the diagnosis of uterine AVM. These
      noninvasive techniques should be performed initially when this rare disease is
      suspected.

PMID- 12053107
TI  - Visual retinocortical function in dementia of the Alzheimer type.
AB  - BACKGROUND: Some histological investigations have reported anomalies in the
      primary visual pathways of individuals with dementia of the Alzheimer type (DAT),
      while others have suggested that these visual structures are spared by the
      disease process. OBJECTIVES: This study was conducted to address this issue of
      substantial controversy. We determined in vivo whether DAT alters the functioning
      of the primary visual pathways by evaluating pattern-reversal electroretinograms
      (ERGs) and cortical visual evoked potentials (VEPs). METHODS: Twenty-seven
      individuals with mild to moderate DAT and 27 age- and sex-matched control
      subjects were included in the investigation. ERG and VEP recordings were obtained
      from all participants with the use of a clinical electrodiagnostic system.
      Stimulus conditions were biased towards a preferential response from the
      magnocellular and parvocellular subdivisions of the visual system. RESULTS:
      Amplitude and latency of the ERG were not affected by DAT. The VEP amplitude was
      not attenuated in DAT individuals, but there was a delay in the latency of the
      VEPs arising from both magnocellular and parvocellular streams of visual
      processing. CONCLUSION: Our results indicate that while the inner retina appears
      to be spared by the disease process, the visual function is altered upstream in
      the retinocortical visual pathways of individuals with DAT.

PMID- 12053108
TI  - Small bowel enterocyte apoptosis and proliferation are increased in the elderly.
AB  - BACKGROUND: It is known that in the elderly the small bowel does not reveal
      structural and functional deteriorations in normal conditions, whereas the
      absorptive function is impaired in stress conditions. OBJECTIVE: The balance
      between enterocyte apoptosis and proliferation being responsible for the
      maintenance of tissue size, mucosal morphology and function in the
      gastrointestinal tract, the aim of our study was to evaluate the rates of
      enterocyte apoptosis and proliferation in the duodenal mucosa of aged human
      beings in comparison to adults. METHODS: For this purpose, the terminal
      deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine triphosphate nick
      end labelling (TUNEL) technique and immunohistochemistry for MIB-1 detection were
      applied on histological sections of endoscopic duodenal biopsy specimens obtained
      from 12 healthy elderly subjects (mean age 77.6 years; M/F 7/5) and 12 healthy
      adult subjects (mean age 37.7 years; M/F 8/4). Counts were performed, at a
      constant magnification (x200), by computer-aided analysis and the results
      expressed as median percentages of positive enterocytes. RESULTS: The results
      showed a significant increase in enterocyte apoptosis in the elderly (15.3 vs.
      2.1% in the adults, p < 0.001) which was positively correlated (r(s) = 0.65, p <
      0.05) with a significant increase in enterocyte proliferation (37.7 vs. 15.8% in
      the adults, p < 0.0001). CONCLUSIONS: These data suggest that the maintenance of
      mucosal architecture throughout the process of aging is due to either a
      hyperproliferative state or an exaggerated apoptosis with a consequent cellular
      immaturity, which may impair the absorptive function observed in stress
      conditions.

PMID- 12053109
TI  - Malondialdehyde: a possible marker of ageing.
AB  - BACKGROUND: Numerous recent studies have suggested that oxidative damage may be
      important in the ageing process, and lipid peroxidation is an important
      biological consequence of oxidative cellular damage. OBJECTIVE: The aim of this
      work was to analyze the activities of the two protective enzymes, superoxide
      dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) to
      examine the relationship between the ageing process and defence antioxidant and
      lipid peroxidation. METHOD: SOD activity was measured in red blood cells using
      the Minami and Yoshikawa method; CAT activity was measured in hemolysates by the
      Aebi method, and MDA levels were measured in erythrocytes by high-performance
      liquid chromatography. RESULTS: SOD activity shows statistically significant
      differences between newborns and the rest of the sample (ANOVA p < 0.001; Student
      Newman-Keuls test p < 0.001). CAT activity did not show significant differences
      between the age groups. We observed statistically significant differences in MDA
      levels between the different groups (ANOVA p < 0.001; Student-Newman-Keuls test p
      < 0.05). In the regression analysis and rectilinear/curvilinear adjustment
      compared to age, SOD and CAT showed coefficients close to zero (SOD linear =
      0.16; SOD exponential = 0.15; CAT linear = 0.056; CAT exponential = 0.068),
      indicating in that way their independence from age. Only MDA obtained a
      regression coefficient superior to 0.75 (p < 0.05). The best adjustment was
      reached through an exponential expression, giving the following parametric
      relation: MDA = 103.117e(0.0021.AGE). No statistically significant variation in
      SOD and CAT activity and MDA levels, related to sex could be demonstrated.
      CONCLUSIONS: Our data show that old age is associated with an increase in
      systemic oxidative stress.

PMID- 12053110
TI  - A novel mutation in a patient with Werner's syndrome.
AB  - BACKGROUND: Werner's syndrome, a rare autosomal recessive disorder, is
      characterized by features of premature aging. Seventy-five percent of the alleles
      of Japanese patients with Werner's syndrome have one of three major mutations.
      OBJECTIVE: To determine the genotype of a patient with Werner's syndrome.
      METHODS: We diagnosed Werner's syndrome in a 47-year-old Japanese man who had
      juvenile cataracts, skin sclerosis and hyperpigmentation of the feet, a high
      pitched voice, characteristic bird-like appearance of the face with a beak-shaped
      nose, thinning of the skin over the whole body and hyperkeratoses on the soles of
      the feet, hyperlipidemia, and diabetes mellitus. None of his immediate family had
      entered into a consanguineous marriage. He had undergone surgery to treat
      duodenal perforation. We screened his family for three major mutations (mutations
      1, 4, 6) in the WRN gene by polymerase chain reaction-restriction fragment length
      polymorphism. Automated DNA sequencing fluorescence-labeled dideoxy terminators
      proceeded for abnormally migrating bands. RESULTS: The patient and his mother had
      mutation 1 (nonsense mutation) in one chromosome. Although mutations 4 and 6 were
      undetectable, screening for mutation 4 revealed an abnormally migrating band.
      Consequently, we discovered a novel 4-bp deletion in exon 25 only in the patient.
      This mutation was not detected in any other family member. CONCLUSION: This is
      the first description of a patient with Werner's syndrome who has a compound
      heterozygote of mutation 1 and a novel deletion mutation.

PMID- 12053111
TI  - Feasibility, acceptability and internal consistency reliability of the nottingham
      health profile in dementia patients.
AB  - BACKGROUND: Few studies have evaluated subjective health status in dementia
      patients. OBJECTIVES: The aim of the study was to determinate the feasibility,
      acceptability and internal consistency reliability of measuring subjective health
      status in dementia patients with the Nottingham Health Profile (NHP). DESIGN: The
      French version of the NHP was administered to 145 dementia patients and their
      proxies (family caregivers and formal caregivers). MEASURES: The refusal rate,
      type of administration and time for completion were used as indicators of
      feasibility. Internal consistency reliability was determined with Cronbach's
      alpha coefficient and test-retest reliability assessed with the intraclass
      correlation coefficient for test-retest values. The measurements obtained were
      compared by source of information (patient and proxies). RESULTS: The 145
      subjects had an average age of 82 and 78% were women. 73% had a Mini-Mental State
      <16. Ninety-four percent of the items were correctly filled in, but an
      interviewer had to be present because of problems in attention or comprehension.
      The test-retest reliability for subjects was good (rho < 0.7), but response
      agreement between patients and their proxies was just acceptable for physical
      domains (rho < 0.6) and poor for psychological and social domains (rho < 0.4).
      CONCLUSIONS: Self-rating of perceived health status by dementia patients seems
      feasible with the questionnaire with adaptations in the administration, but other
      methods are needed to approach the more subjective domains of the quality of
      life.

PMID- 12053112
TI  - Dementia as a predictor of functional disability: a four-year follow-up study.
AB  - BACKGROUND: Prospective studies have shown that cognitive impairment is a strong
      and consistent risk factor of physical disability. However, cognitive impairment
      has been based on the result of a single screening tool. OBJECTIVE: To
      investigate the role of cognition in the subsequent incidence and decline of
      functional disability in basic activities of daily living (ADL) and instrumental
      activities of daily living (IADL) after a full assessment of dementia. METHODS: A
      group of 1,358 Japanese atomic bomb survivors aged 61 years or older who lived in
      the community or in institutions in Hiroshima City were followed for 4 years.
      During the baseline survey (1993-1995), subjects were administered a screening
      test for cognitive impairment. Those suspected of dementia underwent a series of
      cognitive tests (Hasegawa's dementia scale, Clinical Dementia Rating) and a
      neurological examination. The diagnosis of dementia was made according to DSM-III
      R criteria. Study subjects were questioned about their reported ADL and their
      IADL. During the follow-up period, deaths were recorded and a follow-up survey
      (1997-1999) used to assess ADL and IADL performance. RESULTS: Dementia, even
      after adjustment for age, sex and history of stroke, was a strong predictor of
      functional disability, as indicated by ADL (odds ratio, OR = 14.0; confidence
      interval, CI = 5.4-36.3), IADL (OR = 10.1, CI = 2.2-46.4), and also by assessment
      of decline in ADL (OR = 9.8, CI = 4.2-22.8) or IADL status (OR = 3.9, CI = 1.8
      8.3). CONCLUSION: Dementia is an important determinant of functional status.
      Deterioration in ADL is more significant than deterioration in IADL, suggesting
      that factors other than cognition, such as motivation or perceptual, sensory and
      motor abilities, may be important in IADL performance. This study confirms
      previous findings on risk factors that affect functional ability and extends our
      knowledge by examining several criteria of function that are important in the
      daily lives of elderly people.

PMID- 12053113
TI  - Lifestyle factors and health outcomes in elderly Hong Kong chinese aged 70 years
      and over.
AB  - BACKGROUND: Although increasing emphasis is being placed on strategies for
      successful aging, few studies have examined the relationship between lifestyle
      factors and mortality and other health outcomes in the old-old population.
      OBJECTIVE: To examine the impact of physical activity, dietary habits, smoking,
      and alcohol consumption on 3-year mortality and other health outcomes. METHODS:
      2,032 Chinese subjects aged 70 years and older (mean age 80 years) were recruited
      territorywide by proportional random sampling and followed for 3 years. Baseline
      information was obtained by interview on level of physical activity, dietary
      habits (frequency of consumption per week of major food groups), alcohol
      consumption, and smoking habits. Outcome measures include mortality, self
      perceived health status, frequency of hospitalization, geriatric depression
      score, and development of new diseases (stroke, heart disease, hypertension,
      diabetes mellitus, fractures). Logistic regression was used to examine the
      effects of lifestyle factors on each health outcome, with and without adjustment
      for age and baseline health status. RESULTS: The mortality risk is reduced with
      increasing physical activity, daily fish intake and moderate alcohol consumption,
      and avoidance of smoking; hospitalization is inversely associated with increasing
      activity; better self-perceived health is associated with moderate alcohol
      consumption and a non-smoking status, and there is an inverse relationship
      between depressive symptoms and increasing activity and moderate alcohol
      consumption. After adjustment for age and baseline health status, higher levels
      of physical activity are associated with decreased mortality and hospitalization;
      non-smokers have reduced mortality and a better self-perceived health, and
      moderate alcohol consumption is also associated with better self-perceived
      health. CONCLUSION: Lifestyle factors may influence health outcomes even in the
      old-old population.

PMID- 12053114
TI  - Foot dimensions of elderly people with and without diabetes mellitus - a data
      basis for shoe design.
AB  - BACKGROUND: Injuries from footwear are common in elderly people, particularly in
      those with diabetes mellitus and polyneuropathy. A common cause is a mismatch
      between foot and shoe. OBJECTIVE: To assess the length and the breadth of the
      feet by an automatic measuring device in 568 patients with diabetic
      polyneuropathy and in 100 nondiabetic control subjects of the same mean age of 64
      years. RESULTS: While the foot length in all cases matched well with the size of
      the normal footwear available on the market, more than two thirds of the feet
      were considerably broader than the normal footwear available. The foot breadth
      correlated variably with the foot length. Tables of foot dimensions for men and
      women are provided over the complete range of shoe sizes. CONCLUSIONS: This
      anthropometric data set on feet, which is the first conducted in elderly people,
      proves that most feet of elderly people with or without diabetic neuropathy do
      not fit ordinary casual footwear. Therefore, the construction of shoes according
      to the anthropometric data of elderly people is required in order to prevent foot
      injuries in this particular population.

PMID- 12053115
TI  - Ischaemic hepatitis in the elderly.
AB  - BACKGROUND: Ischaemic hepatitis is centrilobular necrosis which is usually
      associated with an acute cardiovascular event and in a general hospital setting
      has been considered to be a rare condition. It is though thought to be frequently
      unrecognized, which is important as it has implications for both investigations
      and drug therapy. Previous reports have not focused on the elderly. OBJECTIVES:
      (1) To determine the incidence of ischaemic hepatitis in elderly patients
      admitted to a Department of Geriatric Medicine and (2) to assess both the
      clinical and biochemical features of the condition. METHODS: 1,905 elderly
      patients (1,270 F, 635 M) admitted consecutively to our department over a 2-year
      period were assessed prospectively. All were aged > or =65 years (mean 78, range
      65-98). Ischaemic hepatitis was diagnosed by a rapid development of abnormal
      liver function tests of hepatocellular type in acutely ill patients in whom a
      fall in blood pressure occurred and other causes of liver dysfunction were
      excluded. The admission, lowest and subsequent blood pressures were recorded.
      Daily renal and liver function tests, including prothrombin times, were measured
      during the acute illness. RESULTS: Nineteen patients (1%) developed ischaemic
      hepatitis. The clinical picture was dominated by the causal condition, the
      commonest being left ventricular failure (12 patients). The mean fall in
      systolic, diastolic and mean blood pressures were 61, 44 and 48 mm Hg,
      respectively. Within 3 days the alanine aminotransferase increased to more than 5
      times normal and there were marked elevations of the lactic dehydrogenase. In
      those who survived, the liver enzymes returned to normal within 7-22 days (mean
      13). The prothrombin time was prolonged to >20 s in 6 patients (32%). Six
      patients died, 5 from left ventricular failure; the mean creatinine in 5 of those
      who died was 244 micromol/l (range 174-355) and in each the urea was >25
      micromol/l. CONCLUSION: Ischaemic hepatitis is an uncommon but not rare condition
      in elderly patients admitted acutely to a Department of Geriatric Medicine. There
      was a dramatic rise in liver enzymes which in survivors returned to normal within
      3 weeks. Clinical features were dominated by the causal condition and a third of
      the patients died.

PMID- 12053116
TI  - Colonic transit time in diabetic and nondiabetic long-term care patients.
AB  - BACKGROUND: Constipation is a frequent health concern for elderly people. The
      increased incidence of constipation with age is mainly based on self-reported
      data. Only a few studies have examined this problem objectively and even fewer
      have carried this out in the special subpopulation of frail elderly patients.
      OBJECTIVE: The aim of this study was to examine colonic transit time (CTT) in
      frail elderly patients. We also attempted to compare CTT in diabetics and
      nondiabetics within this population. METHODS: 45 frail elderly patients, all
      immobile with and without diabetes mellitus, residing permanently in long-term
      geriatric departments were recruited for the study. All patients underwent
      segmental and total CTT studies using radiopaque markers. The segmental CTT was
      calculated separately for the four segments of the colon (ascending, transverse,
      descending, and rectosigmoid) and for the total transit time which was the sum of
      all four segments. RESULTS: The average CTT was extremely prolonged in all
      patients included in this study. In the diabetics the CTT was even longer with a
      mean total transit time of 200 +/- 144 h as compared with 143 +/- 95 h in the
      controls. The difference was not statistically significant. For each segment
      tested, the CTT was shorter in the control group, but these differences did not
      reach statistical significance. CONCLUSIONS: The CTT is prolonged in immobile
      frail elderly patients. No significant differences were noted between diabetic
      and nondiabetic patients.

PMID- 12053118
TI  - Retinoic acid regulation of mesangial cell apoptosis.
AB  - Retinoic acid (RA) is recently used for the treatment of experimental glomerular
      diseases. However, mechanisms underlying its therapeutic effects are largely
      unknown. We recently reported that RA has the potential for protecting certain
      cells from particular injury. A typical example is its effect on oxidant-induced
      apoptosis of mesangial cells. Mesangial cells exposed to hydrogen peroxide
      undergo apoptosis through activation of the c-Jun N-terminal kinase activator
      protein 1 pathway. RA dramatically inhibits this process via suppression of c
      fos/c-jun expression and inhibition of the c-Jun N-terminal kinase activation.
      The anti-apoptotic effect of RA is mediated by both nuclear receptor dependent
      and nuclear receptor independent mechanisms and is, at least in part, mediated by
      induction of mitogen-activated protein kinase phosphatase 1. In this review, we
      briefly summarize the current knowledge on molecular mechanisms involved in the
      anti-apoptotic effects of RA.

PMID- 12053117
TI  - Timed instrumental activities of daily living tasks: relationship to cognitive
      function and everyday performance assessments in older adults.
AB  - BACKGROUND: We live in a world where information is presented in a time-limited
      fashion and successful adaptation is dependent on time-limited responses. Slowed
      visual-processing speed is common among older adults. Its impact on everyday task
      performance is not clearly understood. OBJECTIVE: The goal was to determine
      whether visual-processing speed, as well as memory and inductive reasoning, are
      independently associated with the time required by older adults to complete
      instrumental activities of daily living typical of everyday life. METHODS: Five
      timed instrumental activities of daily (TIADL) tasks were administered to 173
      older adults (ages 65-90 years) along with assessments of visual-processing
      speed, memory, and inductive reasoning. The dependent variable was the time
      required to perform the task (e.g., finding a telephone number, making change,
      finding and reading the ingredients on a can of food, finding food items on a
      shelf, reading instructions on medicine container). Medical and functional
      comorbidities known to affect task performance were measured in order to adjust
      for their impact on the dependent variable. Other measures of everyday task
      competence (Everyday Problems Test, Observed Tasks of Daily Living, questionnaire
      on IADL difficulties) were also administered in order to determine to what extent
      existing measures of everyday performance are associated with TIADL performance.
      Test-retest reliability of the TIADL score was assessed in a separate sample.
      RESULTS: Although memory and reasoning were crudely related to the time needed to
      perform the TIADL tasks, only processing speed was independently associated with
      TIADL scores. Those older adults with slow processing speed were more likely to
      require longer times to complete everyday tasks. Previously developed measures of
      everyday task competence (e.g., Everyday Problems Test, Observed Tasks of Daily
      Living) based on accuracy scoring did not strongly predict TIADL performance.
      CONCLUSION: These results suggest a unique role for an everyday competence test
      that focuses on the timely completion of everyday tasks, rather than on an
      assessment of accuracy alone. TIADL measures may prove useful in evaluating the
      everyday effectiveness of cognitive interventions targeted at increasing
      information-processing speed.

PMID- 12053119
TI  - Urinary stone formation: Dent's disease moves understanding forward.
AB  - Renal stones form in the late collecting duct in a complex milieu involving salts
      and protein components of the urine together with direct interactions at the
      epithelial cells lining the duct. The operation of newly discovered physiological
      controls that limit crystal formation by feedback mechanisms which sense the
      luminal environment are discussed. Adhesion at the epithelial surface and
      intracellular processing of crystals comprise a previously unrecognised mechanism
      for limiting crystal growth, which may be disrupted resulting in disease. Dent's
      disease is discussed as a paradigm of a complex renal tubular disease resulting
      in renal stone formation. Defects in endosomal acidification, due to ablation of
      the CLC-5 voltage-gated Cl- channel, result in defects in both proximal and
      collecting duct endosomal traffic leading to stone formation.

PMID- 12053120
TI  - Matrix metalloproteinases and their inhibitions in experimental renal scarring.
AB  - Renal fibrosis is characterised by an excessive accumulation of extracellular
      matrix (ECM) proteins. Evidence suggests that this results from both increased
      ECM synthesis and a reduced degradation. Here, we determine changes in the matrix
      metalloproteinases (MMP) and their tissue inhibitors (TIMP) in relation to ECM
      production and the progression of renal fibrosis in subtotally nephrectomized
      (SNx) rats. Groups of 4-6 SNx or sham-operated male Wistar rats were sacrificed
      between days 7 and 120 following surgery. Total RNA was analysed by Northern
      blotting. Messenger RNA for collagens I (+710%), III (+674%), and IV (+358%) were
      significantly (p < 0.05) raised by day 7 and remained elevated over the 120 days.
      Significant (p < 0.05) increase in fibronectin, laminin and heparan sulfate
      proteoglycan mRNAs occurred latter at days 60 (+224%), 120 (+210%), and 120
      (+256%), respectively. Increases (p < 0.05) in mRNA for MMP-1 (+360%) and MMP-2
      (+239%) occurred from day 7 with MMP-1 reaching +881% by day 120. MMP-3 and -9
      showed no change. Zymography on day 90 remnant kidneys showed mRNA changes were
      translated into active MMP-1 (+1,700%) and MMP-2 (+440%), p < 0.05. TIMP-1 mRNA
      was also raised (+548%, p < 0.05) by day 7 and remained elevated, while TIMP-2
      mRNA levels only reached significance by day 120 (+165%). In contrast, TIMP-3
      mRNA was decreased by day 30 (p > 0.05) and dropped to 27% of control by day 120.
      However, Western blot analysis of TIMPs 1 and 3 at day 90 showed a 5- and 4-fold
      increase respectively, while TIMP-2 levels were not significantly altered.
      Measurements of overall collagenase activities in remnant kidney homogenates were
      reduced. Using collagen I and IV substrates, proteolytic activity in remnant
      kidneys dropped to 40 and 27% of controls (p < 0.01), respectively. This data
      suggests that reduced MMP activity may contribute towards renal scarring, however
      this is not a result of reduced MMP transcription or activation, but likely to be
      due to the inhibition by TIMPs.

PMID- 12053121
TI  - Historadioautographic localization of oxytocin and V1a vasopressin binding sites
      in the kidney of developing and adult rabbit, mouse and merione and of adult
      human.
AB  - The localization of oxytocin (OT) binding sites and vasopressin (VP) binding
      sites of the V1a subtype was investigated by radioautography in kidneys of
      rabbits, mice and meriones during postnatal development and in the adult, and in
      the human kidney. Kidney sections were incubated in the presence of selective
      radioiodinated OT and V1a antagonists, respectively. The localizations were
      compared with those previously described in the rat. The main finding of the
      study was the almost constant presence in the cortex of V1a binding sites in the
      connecting tubule, the cortical collecting duct and in the juxtaglomerular
      apparatus (on the intra- and extraglomerular mesangium and the afferent
      arteriole). This distribution suggests an interaction of VP via V1a receptors and
      the kallikrein-kinin system in the kidney. OT binding sites, in comparison with
      V1a binding sites, were fewer and less constantly detectable in the kidney of the
      different species. In the mouse, their presence on the limbs of Henle's loop in
      the medulla points to the possibility of their involvement in the medullary
      concentrating process. In the kidneys of the various species, OT and V1a binding
      sites occurred always in differential structures. In contrast, in the human
      kidney cortex, a colocalization of OT and V1a binding sites was almost constantly
      observed. This raises the question as to the specificity of the neurohypophysial
      hormone receptors in the human kidney.

PMID- 12053122
TI  - Ionic radiocontrast media disrupt intercellular contacts via an extracellular
      calcium-independent mechanism.
AB  - Direct cytotoxic effects of radiocontrast (RC) agents have been implicated in
      radiocontrast nephropathy (RCIN). The interaction between extracellular calcium,
      which plays a central role in intercellular contacts, and the in vitro toxicity
      of RC was tested in Madin-Darby canine kidney (MDCK) cell monolayers grown on
      permeable supports. Cell viability was determined by trypan blue exclusion. The
      function of intercellular junctions was assessed by measuring the electrical
      transmonolayer resistance (TMR). The cell contacts were examined with indirect
      immunofluorescence microscopy using antibodies against the junctional proteins E
      cadherin, ZO-1 and occludin. The ionic RC agents diatrizoate and ioxaglate (74 mg
      iodine/ml), but not the nonionic compounds iohexol or iodixanol, decreased
      ionized calcium (Ca2+) in the incubation media from 1.48 +/- 0.04 mM (control) to
      0.89 +/- 0.06 mM (diatrizoate), respectively to 1.05 +/- 0.08 mM (ioxaglate).
      Diatrizoate, and to a lesser extent ioxaglate, reduced the number of viable MDCK
      cells and showed a redistribution of the E-cadherin, ZO-1 and occludin
      immunofluorescence signal with a parallel decrease of the TMR indicating an
      impaired monolayer integrity. A similar reduction of extracellular Ca2+ through
      EGTA failed to reproduce these effects. Conversely, raising Ca2+ in diatrizoate
      containing media to control levels did not abrogate its toxicity. In conclusion,
      the ionic RC agents diatrizoate and ioxaglate, but not the nonionic compounds
      iohexol or iodixanol, reduce extracellular Ca2+ in vitro. However, this reduction
      of Ca2+ does not explain their cytotoxic effects which could contribute to the
      pathogenesis of RCIN in vivo by opening intercellular junctions.

PMID- 12053123
TI  - Nucleosome effects on mesangial cell matrix and proliferation: a possible role in
      early lupus nephritis.
AB  - BACKGROUND: Oligonucleosomes (ON) have been demonstrated in the circulation and
      biopsies of lupus nephritis patients. Their presence as immune complexes is an
      early and persistent finding in lupus nephritis as are changes in mesangial
      matrix. Since ON competitively bind to glomerular mesangial cells (MC) in a
      receptor-like fashion, the purpose of our study was to investigate what effects
      ON have on MC matrix and proliferation. METHODS: Rat and mouse MCs grown with ON
      or DNA for 1 week were dissociated from their matrices with Triton-X and their
      proteins were determined. MC collagen production, using collagenase sensitive 3H
      proline incorporation, was measured after 48-hour incubation with ON and DNA.
      Similar experiments using 10-fold excess DNA were done to assess its blocking
      effect on ON induced collagen synthesis. ON interaction with matrix was evaluated
      by incubated 125I-ON with MC matrix grown with ON or media alone for 1 week.
      RESULTS: MCs stimulated by ON but not DNA significantly increased total matrix
      protein, total collagen and specifically, collagen type I synthesis. DNA
      inhibited ON-stimulated collagen synthesis. MC matrix incubated with ON binds 3
      times more 125I-ON than matrix generated in media alone. Histone, a major
      component of nucleosomes, significantly increased 3H-thymidine incorporation.
      CONCLUSIONS: Oligonucleosomes, both qualitatively and quantitatively, influence
      mesangial cell function. These findings for the first time suggest ON to be
      pathogenic independent of their IC construct. DNA inhibition of ON induced
      mesangial matrix changes suggests participation of the ON/DNA receptor. Increased
      production of collagen type I may contribute to glomerulosclerosis.

PMID- 12053124
TI  - The identification of renal cell carcinoma as a target for allogeneic based
      cancer immunotherapy.
AB  - Renal cell carcinoma tumor cells are intrinsically resistant to chemotherapy, but
      unlike most solid tumors, may be susceptible to immune-based therapy. Because
      powerful immune effects can be generated against hematological malignancies
      following allogeneic stem cell transplantation, we investigated for similar anti
      tumor responses in patients with metastatic renal cell carcinoma following the
      transplantation of an allogeneic immune system from a healthy HLA-matched family
      donor. Early laboratory and clinical results have demonstrated that following a
      reduced-intensity allogeneic stem cell transplant, donor T-cell mediated anti
      tumor effects, resulting in sustained and sometimes complete tumor regression,
      can be generated against renal cell carcinoma (RCC) refractory to conventional
      cytokine-based therapy. Early data indicate that cytotoxic T cells of donor
      origin are the mediators of these anti-tumor effects. These preliminary studies
      provide additional evidence supporting the susceptibility of RCC to immune attack
      and lay the foundation for future targeted allo-immune-based cancer strategies.

PMID- 12053125
TI  - Increased blood-brain barrier permeability in white matter lesions of
      Binswanger's disease evaluated by contrast-enhanced MRI.
AB  - We investigated blood-brain barrier (BBB) permeability in white matter lesions of
      Binswanger's disease (BD) with contrast-enhanced MRI. Three subject groups were
      studied: 17 patients with BD and periventricular hyperintensities (PVH) on MRI,
      10 patients with ischemic cerebrovascular events and with PVH but no dementia,
      and 14 age-matched control subjects without PVH. BBB permeability was quantified
      by calculation of T(1) change defined as [(T(1post) - T(1pre))/T(1pre)] x100,
      where T(1pre) and T(1post) represent the T(1) relaxation times before and after
      Gd-DTPA administration. T(1) change in PVH of BD patients significantly decreased
      in comparison with that observed in PVH of the nondemented patients and in normal
      white matter of the control subjects, but no significant T(1) change was observed
      between the PVH of the nondemented patients and normal white matter of the
      controls. There was a significant correlation between the Mini-Mental State
      Examination score and T(1) change for areas of PVH in BD. These results suggest
      that BBB permeability increases in areas of PVH in BD and that a BBB dysfunction
      is related to a progression of cognitive impairment.

PMID- 12053126
TI  - Relation between plasma homocysteine and Alzheimer's disease.
AB  - OBJECTIVE: Several studies have shown that plasma total homocysteine (tHcy)
      concentration is elevated in Alzheimer's disease (AD). However, it is not clear
      whether elevated plasma tHcy is a primary cause or a consequence of AD. METHOD:
      To elucidate this question, we have analysed plasma homocysteine and its
      determinants in patients with early (EOAD)- and late-onset AD (LOAD) and compared
      the findings with those in vascular dementia (VaD) and age- and sex-matched
      control subjects. RESULTS: One of the main findings in the present study is that
      in EOAD there is no change in the levels of either plasma tHcy or its
      determinants compared with an age- and sex-matched control group. The fact that
      plasma tHcy concentration is normal in EOAD thus indicates that elevated plasma
      tHcy is not the primary cause of the disease. Another main finding is that
      patients with mixed dementia (AD and VaD) and patients with VaD showed
      significantly increased plasma tHcy concentration compared with controls and that
      plasma tHCy concentration in patients with LOAD and a history of additional
      cardiovascular disease was elevated compared both with AD patients without such a
      history and with the controls. Thus, there is an association between elevated
      plasma tHcy and vascular disease. A third main finding is that patients with AD
      who were followed up for several years showed a clinical deterioration of
      dementia and an elevation of plasma tHcy concentration. This finding likewise
      supports the notion that elevated plasma tHcy is not the primary cause of the
      disease. CONCLUSIONS: The findings suggest that elevated plasma tHcy is not the
      primary cause of the disease. Furthermore, the findings indicate that elevated
      plasma tHcy might be a reflection of concomitant vascular disease in AD patients.

PMID- 12053127
TI  - Familial frontotemporal dementia associated with a novel presenilin-1 mutation.
AB  - We report a kindred with three cases of dementia. The proband presented with
      forgetfulness and personality changes at age 56, followed shortly thereafter by
      behavioral dyscontrol, hyperphagia, hypersexuality, delusions, illusions,
      disinhibition and double incontinence. Neuroimaging studies were consistent with
      frontotemporal dementia (FTD). In one allele, an arginine insertion at codon 352
      in the presenilin 1 (PSEN1) gene was identified; no mutation was identified in
      the amyloid precursor protein or tau genes. We conclude that the clinical
      features of the Kluver-Bucy syndrome and FTD can be associated with PSEN1
      mutations. Furthermore, presenilin analyses may be helpful to characterize
      kindreds with familial dementing illnesses regardless of the phenotype,
      particularly if no tau mutation is present.

PMID- 12053128
TI  - Caudate nucleus dopamine d(2) receptors in vascular dementia.
AB  - Caudate nucleus dopamine (DA) D(2) receptors were studied in patients with
      vascular dementia (VaD) and in a control group using [(3)H]raclopride as a
      radioligand. There was no significant difference in the number of DA D(2)
      receptors in the VaD group as compared with controls. The binding affinity was
      significantly lower in the VaD group. When the VaD group was subdivided into
      subjects with or without neuroleptic treatment, there were no differences in the
      numbers of receptors as compared with controls, and the significant differences
      in binding affinity remained for both VaD subgroups. The present results are
      discussed with reference to the previous finding of a reduced density of caudate
      nucleus DA uptake sites in the same VaD group and to results from studies on DA
      D(2) receptors in Alzheimer's disease and Parkinson's disease.

PMID- 12053129
TI  - Neuropsychological deficit in early subcortical vascular dementia: comparison to
      Alzheimer's disease.
AB  - To further clarify the cognitive syndrome in subcortical vascular dementia (VaD),
      we investigated 20 patients with early-stage VaD as compared with 30 patients
      with Alzheimer's disease (AD) and 22 normal controls using episodic memory,
      attention/executive function and language tests. The patient groups were closely
      matched in terms of age, education and severity of dementia. The VaD patients had
      a significantly better free recall, cued recall and recognition memory than AD
      patients, the recognition being within normal limits in VaD. In addition, VaD
      patients had a greater number of perseverative errors during the Modified Card
      Sorting test, while AD patients exhibited more perseverations of semantic
      fluency. The results of retrieval deficit syndrome and increased number of
      perseverations during tasks sensitive to frontal lobe function are in agreement
      with the studies emphasizing the importance of frontal dysfunction in subcortical
      VaD. These findings are relevant for the early diagnosis of VaD and might be
      useful in the differential diagnosis with AD.

PMID- 12053130
TI  - Posterior cortical atrophy: clinical characteristics and differences compared to
      Alzheimer's disease.
AB  - BACKGROUND: Predominant and progressive complex visual disorders are often due to
      posterior cortical atrophy (PCA), a rare early-onset dementing syndrome
      presenting with visual complaints. In clinicopathological studies, PCA is most
      commonly considered a form of Alzheimer's disease (AD); no prior study has
      evaluated clinical differences between PCA and AD. METHODS: This study identified
      15 patients who presented with progressive complex visual disorders and
      predominant occipitoparietal hypoperfusion on SPECT. These patients were
      retrospectively compared on clinical variables with 30 patients with clinically
      probable AD matched for gender, age and duration of illness. RESULTS: The PCA
      patients presented with alexia, elements of Balint's syndrome, apperceptive
      visual agnosia, dressing apraxia and environmental disorientation along with
      elements of Gerstmann's syndrome. Compared to the AD patients, the 15 PCA
      patients (mean age of onset 58 years, range 51-64) had significantly better
      verbal fluency, less memory difficulty, more depression and greater insight into
      their illness but similar familial and apolipoprotein E risk factors. In the PCA
      patients, MRI often showed occipitoparietal atrophy without detectable
      mesiotemporal atrophy. CONCLUSIONS: PCA is a distinct clinical syndrome and not
      just AD with prominent visual deficits. Compared to AD controls, PCA patients
      have better language and memory but more insight and depression and more
      posterior atrophy on MRI. These results indicate clinical criteria for the
      diagnosis of PCA and recommend specific interventions such as visual aids and
      antidepressant medications. Similar risk factors and course suggest that PCA is
      most commonly an early-onset posteriorly shifted AD variant.

PMID- 12053132
TI  - Auditory Function and Dysfunction: Molecular and Physiological Mechanisms.
      Proceedings of a meeting. Auckland, New Zealand, August 2001.

PMID- 12053133
TI  - Molecular studies of hair cell development and survival.
AB  - The development of hair cells in both the auditory and vestibular sensory
      epithelia is a complex process that involves the coordinated expression of many
      regulatory proteins. Among these is the POU-domain transcription factor Brn-3.1.
      This factor is expressed in hair cell precursors immediately after commitment to
      the hair cell fate, and continues throughout life. Deletion of this factor in
      mice leads to failure of hair cell differentiation during development, and to the
      death of a majority of the undifferentiated cells. Normal expression of Brn-3.1
      is required for adult hair cell survival as well, since a mutation in this gene
      causes dominant, late-onset, inherited hearing loss in humans. The timing of the
      onset of Brn-3.1 expression suggests that factors regulating its expression may
      be involved in fate determination of hair cells. Moreover, genes that are
      themselves directly regulated by Brn-3.1 appear to play critical roles in hair
      cell development and survival.

PMID- 12053131
TI  - Candidate gene association studies in sporadic Alzheimer's disease.
AB  - The genetics of Alzheimer's disease (AD) is complex. Three genes (amyloid
      precursor protein, presenilin 1 and presenilin 2) have been described in the
      relatively rare, early-onset, autosomal dominant familial form of AD. In the
      common, non-familial (sporadic) late-onset AD, the major known genetic risk
      factor is the epsilon4 allele of the apolipoprotein E (APOE) gene. However, at
      least half of the people who develop AD do not carry this allele, and not all
      people who do carry this allele develop AD even if they live to an old age.
      Therefore, approximately 30 other candidate genes involving a protein in a
      critical pathway in the pathogenesis of disease (principally interaction with
      amyloid-beta, oxidative stress and inflammation/apoptosis) have been considered
      as risk factors for sporadic AD. Then these genes have been sequenced in search
      of genetic variability or polymorphisms, and each putative polymorphism has been
      reported to alter the risk of AD either directly or by an interaction with the
      APOE epsilon4 allele. However, positive-association studies with these candidate
      genes have not been consistently confirmed.

PMID- 12053134
TI  - Connexins and gap junctions in the inner ear.
AB  - Mutations in the genes for three different isotypes of the gap junction channel
      protein connexin are associated with deafness. This indicates an important role
      for gap junctions in auditory function and provides an opportunity to explore
      structure-function relationships in the connexin molecule. We have been examining
      the distribution of gap junctions and the pattern of connexin expression in the
      mature inner ear and during development, and the effect of specific mutations on
      the processing and functionality of the expressed connexin proteins in an in
      vitro system.

PMID- 12053135
TI  - Current issues in cochlear gene transfer.
AB  - Cochlear gene therapy represents a potential experimental and therapeutic tool to
      understand and treat deafness. In designing cochlear gene transfer studies, the
      chosen route of delivery of vector and the choice of gene therapy vector have to
      be given careful consideration. Several different routes of delivery have been
      tested in our laboratory including infusion with osmotic minipump, direct
      microinjection into the cochlea and application of vector-transgene complex
      soaked Gelfoam((R)) into the direct contact with the round window membrane. In
      our experience, the latter is an easy, safe and atraumatic technique to deliver
      gene into the cochlea. A number of different gene transfer vectors have been
      investigated in vivo for their efficacy, utility and safety in intracochlear gene
      transfer. Vectors successfully studied include cationic liposomes, adeno
      associated virus, adenovirus, lentivirus, herpes simplex virus and vaccinia
      virus. While the viral vectors offer clear experimental advantages, human gene
      therapy in the future will likely utilize nonviral vectors to maximize safety.
      Finally, safety issues regarding dissemination of gene transfer vectors beyond
      the target cochlea will need to be adequately addressed.

PMID- 12053136
TI  - Stress pathways in the rat cochlea and potential for protection from acquired
      deafness.
AB  - Noise overstimulation will induce or influence intracellular molecular pathways
      in the cochlea. One of these is the 'classical' stress response pathway involving
      heat shock proteins. Hsp70 is induced in the cochlea by a wide variety of
      stresses including noise, hyperthermia and ototoxic drugs. When a stress that
      induces Hsp70 is applied to the cochlea, there is protection from a subsequent
      noise that would normally cause a permanent hearing loss. An upstream regulator
      of heat shock protein transcription, heat shock factor 1, is expressed in the
      cochlea and activated by stress. Mice lacking this heat shock factor have reduced
      recovery from noise-induced hearing loss. The same noise exposure that induces
      Hsp70 also increases the level of glial cell line-derived neurotrophic factor in
      the cochlea. Moreover, when this neurotrophic factor is applied into the
      perilymph of scala tympani prior to a noise exposure there is a significant
      reduction in hair cell loss and hearing loss. With the potential for activation
      of multiple pathways in the response to noise, gene microarrays can be useful to
      examine global gene expression. Initial studies examined differential gene
      expression immediately following a mild noise exposure (from which there is
      complete recovery) versus an intense noise (giving profound permanent deafness).
      Differential expression of several immediate early genes was found following the
      intense but not the mild noise exposure.

PMID- 12053137
TI  - Viral-mediated gene transfer to study the molecular physiology of the Mammalian
      inner ear.
AB  - Several classes of viral vectors including adenovirus, adeno-associated virus,
      herpes simplex virus, lentivirus and vaccinia virus have been reported to infect
      cells of the inner ears of mammals and may be useful for protein manipulation and
      therapeutic purposes. We have screened a few of these for use as vectors to
      mediate gene transfer into the sensory hair cells of organotypic cultures from
      the neonatal mouse cochlea and utricle. Recombinant, replication-deficient
      adenovirus has emerged as a useful vector for several reasons: ease of vector
      generation at high titer; efficient hair cell specific infection; robust
      expression of reporter genes and minimal toxicity. Previously, we characterized
      adenovirus infected hair cells using a vector that carried the gene for green
      fluorescent protein (GFP). We screened GFP-positive cells electrophysiologically
      and found that although hair cells survive adenoviral vector infection, their
      mechanosensitivity was compromised. Until recently this has limited the scope of
      adenovirus application to the problems of inner ear physiology and
      pathophysiology. However, a modified adenoviral vector, now available, has been
      reported to have reduced ototoxicity in vivo. The modifications include the
      deletion of the adenoviral genes E1, E3, the viral polymerase, and the
      preterminal protein. We are currently working to characterize viral-mediated gene
      transfer into hair cells of the cultured mouse utricle using this new modified
      adenoviral vector. We have found that hair cells infected with the modified
      vector have intact hair bundles and robust mechanotransduction.

PMID- 12053138
TI  - From gene identification to gene therapy.
AB  - Inner ear disease due to hair cell loss is common, and no restorative treatments
      for the balance and hearing impairment are currently available. To develop
      clinical means for enhancing protection and regeneration in the inner ear, it is
      necessary to understand the molecular basis for hereditary and acquired deafness
      and vestibular disorders. One approach is to identify and characterize genes that
      regulate protection or repair in other systems. For that purpose, we have used
      the differential display assay and compared gene expression between normal and
      acoustically traumatized inner ears of chicks. Several chick cDNAs that were
      identified are considered as candidates for roles in the reparative process that
      follows trauma in the basilar papilla. The mammalian vestibular epithelium has a
      limited regenerative capability. To identify genes that may participate in the
      regenerative response, we have used gene arrays profiling, comparing normal to
      drug-traumatized vestibular epithelia. We identified several genes that are
      differentially expressed in traumatized vestibular epithelium, including several
      insulin-like growth factor-I binding proteins. To use this molecular knowledge
      for enhancing protection and repair in the organ of Corti, it is necessary to
      overexpress the genes of choice in the inner ear. Using viral-mediated gene
      transfer, we overexpressed transgenic glial cell line-derived neurotrophic factor
      and demonstrated a robust protective effect against acoustic and ototoxic inner
      ear trauma. Future identification of the genes that are important for protection
      and regeneration, along with improved gene transfer technology, will allow the
      use of gene therapy for treating hereditary and environmental inner ear disease.

PMID- 12053139
TI  - Mechanisms of cell death in the injured auditory system: otoprotective
      strategies.
AB  - Oxidative stress insults such as neurotrophin withdrawal, sound trauma,
      hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been
      shown to induce apoptosis of both auditory hair cells and neurons. In this paper,
      we review some components of the apoptotic pathways leading to the death of hair
      cells and auditory induced by growth factor withdrawal or cisplatin intoxication:
      (1) reactive oxygen species and free radicals are formed as by-products of
      several metabolic pathways and these molecules can themselves cause cell damage
      by reacting with cellular proteins; (2) activation of caspases, and (3)
      activation of calpain. These mechanisms have several different points at which
      inhibitors could be targeted to protect cells from programmed cell death,
      including the prevention of oxidative stress-induced apoptosis and the activation
      of caspases and calpains.

PMID- 12053140
TI  - Recent advances in understanding aminoglycoside ototoxicity and its prevention.
AB  - Studies over the last decade have left little doubt that reactive oxygen species
      (ROS) participate in the cellular events leading to aminoglycoside-induced
      hearing loss. The evidence ranges from the demonstration of aminoglycoside
      mediated ROS formation in vitro to the prevention of ototoxicity by antioxidants
      in guinea pig in vivo. Here we review a hypothesis of the mechanism of toxicity,
      discuss possible causes underlying the gradient in base-to-apex sensitivity of
      outer hair cells, and present recent results on the adult mouse as a new animal
      model of aminoglycoside ototoxicity and its prevention.

PMID- 12053141
TI  - Protection and regrowth of the auditory nerve after deafness: neurotrophins,
      antioxidants and depolarization are effective in vivo.
AB  - Deafness, with loss of sensory (hair) cells, results in progressive
      pathophysiological changes ending in the degeneration of most auditory nerve
      neurons. It is now possible to consider these events in the broader context of
      anti-apoptotic survival factors in the peripheral and central nervous system. One
      consequence of deafferentation of a neuron is the loss of neurotrophins that can
      lead to a change in oxidative state (formation of free radicals), changes in
      intracellular Ca(2+), and an up-regulation of apoptotic genes. Interventions that
      can modify availability of neurotrophins, [Ca(2+)](I), and/or free radical
      formation or their destructive effects, may preserve the auditory nerve. Some
      interventions (neurotrophins) may also lead to a regrowth of neurites. Studies in
      this area are of basic value and also of immediate clinical interest for the
      application of the cochlear prosthesis to the severe and profoundly deaf, since
      the benefits of this prosthesis are directly dependent on auditory nerve survival
      and the proximity of stimulating electrode to neuron. We, and others, have found
      that auditory nerve degeneration can be prevented by chronic electrical
      stimulation. We have demonstrated in vivo that this effect can be blocked by
      tetrodotoxin, thus indicating that propagated action potentials are a necessary
      condition, and by verapamil (Ca(2+) channel blocker), supporting in vitro studies
      by others, indicating that L-type Ca(2+) channels are necessary for stimulation
      induced rescue of the deafferented auditory nerve. The intensities of electrical
      stimulation required for rescue are at levels sufficient to express the
      intermediate-early gene c-fos which can initiate transcription of anti-apoptotic
      genes and pathways, and up-regulate expression of neurotrophins that may act in
      an autocrine manner to protect the nerve from death. We, and others, have found
      that chronic local delivery (osmotic pump and microcannulation of the inner ear
      fluid spaces) of individual neurotrophins and cocktails of factors can also
      enhance survival of the deafferented nerve, and some can also initiate a regrowth
      of degenerated peripheral processes of the nerve into the region of the destroyed
      sensory epitheliae. Recently, we have shown that this rescue can occur with
      delayed intervention, after degeneration of some neurons has begun, more closely
      mimicking the human clinical situation. Finally, we have shown that interventions
      with antioxidants may also be effective in preventing pathophysiological changes
      of the auditory nerve following deafness. These studies in the auditory periphery
      support the 'neurotrophic factor hypothesis' as proposed as a general mechanism
      underlying neurodegenerative and age-related pathology of the central nervous
      system. Additional animal studies can yield a rational scientific basis to
      justify human trials, with a goal to maintain auditory cell survival and initiate
      and direct fiber growth to the next generation of prosthesis. Intimate contact
      between electrode and a dense population of auditory neurons should greatly
      enhance the benefits of these devices for the profoundly deaf.

PMID- 12053142
TI  - Potential role of purinergic signalling in cochlear pathology.
AB  - Adenosine triphosphate (ATP) is a major intercellular signalling molecule that is
      involved in neurotransmission in the central and autonomic nervous systems,
      regulation of blood flow, and neuroendocrine function. It is also a key
      signalling molecule involved in normal cochlear homoeostasis, regulating hearing
      sensitivity, controlling vascular tone and acting as a candidate neurotransmitter
      at the hair cell afferent synapses. It has also been established that
      extracellular ATP mediates some pathological processes such as inflammation,
      apoptosis and cell proliferation. Evidence for a profound influence of
      extracellular ATP on normal cochlear function offers the tantalizing possibility
      that extracellular purine nucleotides may play a role in disease processes in the
      inner ear. This review draws on the current understanding of the
      pathophysiological role of extracellular ATP in tissues, and the evidence for the
      functional expression of purinergic signalling elements in the inner ear, to
      speculate on the potential role of purine nucleotides in cochlear pathology.

PMID- 12053143
TI  - Molecular diagnosis of deafness: impact of gene identification.
AB  - Recent progress in identifying genes responsible for hearing loss enables the ENT
      clinician to apply molecular diagnosis by genetic testing. This article focuses
      on three genes, which are prevalent and therefore commonly encountered in the
      clinic. GJB2 (connexin 26) is currently recognized as the most prevalent gene
      responsible for congenital hearing loss in many countries. A series of reports
      revealed that different combinations of GJB2 mutations exist in different ethnic
      populations, indicating that ethnic background should be considered when
      performing genetic testing. GJB2 mutations will be of particular interest in
      combination with universal infant hearing screening programs, because it has been
      shown that early identification of hearing loss and early intervention are
      crucial for language development. Progress in genetic analysis has changed the
      concept of diseases. The present review introduces the example of two
      historically distinct categories of disease, Pendred syndrome and nonsyndromic
      hearing loss associated with enlarged vestibular aqueduct, which are currently
      considered to be a continuum of diseases caused by the same gene, PDS. This
      review also emphasizes that some hearing impairment can be prevented. The 1555A-
      >G mitochondrial mutation, the most prevalent mitochondrial mutation found in the
      hearing-impaired population, was found in approximately 3% of the outpatients.
      The 1555A-->G mutation is known to be associated with a susceptibility to
      aminoglycoside antibiotics. There may be a considerably large high-risk
      population and to avoid possible side effects in this group, a rapid mass
      screening system and careful counseling are recommended.

PMID- 12053144
TI  - An animal model of auditory cortex prostheses.
AB  - Experiments aimed at rehabilitating deaf and blind patients with cortical
      prostheses were first conducted decades ago, but epicortical electrodes allowed
      only crude information transfer. Here we report that in Mongolian gerbils with
      electrodes implanted in input layers of the primary auditory cortex, spatial,
      temporal and spatiotemporal variations in intracortical stimulation all lead to
      perceptual differences as evidenced by discrimination training. For some stimulus
      regimes discrimination learning was as fast as with intracochlear stimulation in
      this animal. Intracortical stimulation induced field potentials and 2
      deoxyglucose labeling patterns in primary auditory cortex similar to those
      induced by auditory click or tone stimuli, respectively. Given the common
      organization principles of neocortical areas, these results are presumably also
      of significance to prostheses interfacing with visual cortex.

PMID- 12053145
TI  - Different kinetics in anti-cytomegalovirus immunity reconstitution evaluated by
      lymphocyte proliferation and IFN-gamma production in allogeneic and autologous
      bone marrow transplantation.
AB  - Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased
      risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To
      investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV
      immune reconstitution at 1 and 4 months after BMT and on the day after first CMV
      antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted
      by antigenemia of >or=2 cells. One month after transplant, AUTOBMT recipients
      already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but
      comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV
      antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-gamma secretion (86%),
      whereas this was infrequently seen in ALLOBMT patients (20 and 10%,
      respectively). This early AUTOBMT immune reconstitution was associated with a
      lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT
      patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag
      immune responses. At first antigenemia detection, all 3 AUTOBMT recipients
      already displayed anti-CMV immune functions and 2 cleared the infection without
      therapy, whereas of the 10 ALLOBMT recipients only 1 had positive
      lymphoproliferation. In the latter group, none had IFN-gamma secretion or cleared
      the infection without therapy. Thus, differences in anti-CMV immune
      reconstitution may help to explain the contrasting rates of CMV morbidity between
      ALLOBMT and AUTOBMT patients.

PMID- 12053146
TI  - Analysis of mixed chimerism in patients after allogeneic stem cell
      transplantation using a capillary electrophoresis system.
AB  - We analyzed mixed chimerism (MC) after allogeneic stem cell transplantation (SCT)
      using a capillary electrophoresis system with four kinds of fluorescence-labeled
      primers for microsatellites (D3S1359, D6S89, ACTBP2, HGH). The sensitivities of
      all microsatellites were at least 3%. The present method is sufficiently rapid:
      only 3-4 h are needed to perform all the procedures. For analysis of MC in 30
      patients who had undergone allogeneic SCT, heterozygosity of all microsatellites
      was over 88% and informativeness of ACTBP2 and HGH was over 73%. We analyzed MC
      using this technique to determine whether it was useful for prediction of the
      prognosis of 22 patients who had undergone allogeneic SCT. MC was more frequently
      observed in patients who were treated without total body irradiation (TBI) than
      in patients who were treated with TBI (p = 0.009). MC was also seen in a larger
      percentage of patients without acute graft-versus-host disease (p = 0.027). Six
      patients developed graft failure or relapse among 12 patients with MC. The graft
      failure or relapse was higher in patients with MC than in patients with complete
      chimerism (CC) (p = 0.009) especially if they were over 30 years of age (p =
      0.0005). In contrast, graft failure or relapse was not higher in patients with MC
      compared with patients with CC under 30 years of age (p = 0.78). These results
      show that MC is an important predictive factor, especially in patients over 30
      years of age.

PMID- 12053147
TI  - Outcome of treatment in adult acute lymphoblastic leukemia in southern Brazil
      using a modified german multicenter acute lymphoblastic leukemia protocol.
AB  - Reports on treatment outcomes in adults with acute lymphoblastic leukemia (ALL)
      in Brazil are sparse. To evaluate the outcome of patients with ALL managed by the
      public healthcare system, we studied 42 adults treated from 1990 to 1997 in the
      Division of Hematology at Hospital de Clinicas, Porto Alegre, Brazil. Of these
      patients, 14/42 were females and their median age at diagnosis was 26 (17-64)
      years. The diagnosis of ALL was based on cytological examination of marrow
      smears, and immunophenotypic and cytogenetic studies, when available. Fifty
      percent of the patients expressed CD10, 30% were CD10 negative and CD19 positive
      and 20% expressed T markers. Philadelphia chromosome was found in 4 (7.14%). The
      chemotherapy protocol was adapted from the German Multicenter ALL (GMALL) 02-84
      protocol. The complete remission rate was 93% and the overall survival at 5 years
      was 41%. No particular risk factor was identified in our series. These results
      are comparable to the findings of other international studies.

PMID- 12053148
TI  - Telomerase activity and its correlation with the proliferative potential of bone
      marrow in aplastic anemia in children.
AB  - OBJECTIVE: To explore telomerase activity and its association with the
      proliferative potential of hematopoietic stem cells in bone marrow (BM) in
      patients with aplastic anemia (AA). METHODS: Telomerase activity of mononuclear
      cells separated from BM was determined with the TRAPeze kit. BM specimens from 22
      cases with AA and 7 normal controls were included. SPSS10.0 was applied to
      analyze data derived from telomerase activity and colony-forming unit-granulocyte
      and monocyte. RESULTS: The median telomerase activity level of BM in AA was 2
      fold higher than that in normal controls. There was an inverse correlation in AA
      between telomerase activity and colony-forming unit (r = 0.78, p < 0.05). BM of
      chronic AA expressed higher telomerase than that of acute AA. CONCLUSIONS:
      Telomerase activity in AA was increased and may be the result of the negative
      feedback of hematopoietic potential. Telomerase activity varied between the
      subtypes of AA. Telomerase activity was conversely correlated with the
      proliferative potential of BM in AA.

PMID- 12053150
TI  - Bacteria in blood smears: overwhelming sepsis or trivial contamination.
AB  - It is unusual to find microorganisms in peripheral blood smears, and their
      presence is frequently associated with overwhelming sepsis and consequently a
      poor prognosis. In this report, we demonstrate 4 cases with bacteria in blood
      smears. Two of them had a fatal outcome, but the other 2 were caused by a
      contamination either via the central venous catheter or in vitro, both without
      dramatic outcome. The finding of bacteria in blood smears has to be interpreted
      carefully, and thorough examination of peripheral blood smears may be of great
      importance in the early diagnosis of bacteremia; however, in vitro contamination
      must be excluded.

PMID- 12053151
TI  - Spectral karyotyping refined the identification of a der(Y)t(Y;1)(q11.1 or.2;q12)
      in the blast cells of a patient with atypical chronic myeloid leukemia.
AB  - We report a case of atypical chronic myeloid leukemia who showed leukocytosis
      with immature granulocytes and dysplastic features but no monocytosis or
      basophilia. Cytogenetic analysis by conventional G-banding showed an abnormal
      clone, which was interpreted as 46,X,-Y,+der(?)t(?;1)(?;q?1), and no Philadelphia
      chromosome. Reverse transcription-polymerase chain reaction did not show either
      major or minor BCR-ABL chimeric mRNA. Spectral karyotyping (SKY) and fluorescence
      in situ hybridization (FISH) refined the karyotype to 46,X,der(Y)t(Y;1)(q11.1
      or.2;q12). The der(Y)t(Y;1) abnormality was reported previously in 9 cases and
      associated with myelodysplastic syndrome or chronic myeloproliferative disorders.
      SKY in combination with the standard banding method and FISH may be useful for
      exploring undefined chromosome abnormalities in hematological disorders.

PMID- 12053149
TI  - Interferon-alpha therapy following autologous peripheral blood stem cell
      transplantation for adult T cell leukemia/lymphoma.
AB  - In the present report, we describe a case of adult T cell leukemia/lymphoma
      (ATLL), a 58-year-old woman, successfully treated with interferon (IFN)-alpha
      following autologous peripheral blood stem cell transplantation (auto-PBSCT). The
      patient remains in remission with full performance status for more than 12
      months. Auto-PBSCT reduced the abdominal lymphoma mass and IFN-alpha eliminated
      residual tumor cells, possibly through the induction of specific T-cell subsets
      expressing CD3, CD8 on their surfaces and either IFN-gamma or tumor necrosis
      factor (TNF)-alpha in cytoplasm. We have treated a total of 4 ATLL patients with
      auto-PBSCT, including the case presented herein. All other patients treated with
      auto-PBSCT were not followed by adjuvant chemotherapy or cytokine therapy and
      relapsed within 3 months after auto-PBSCT. This evidence suggests that the
      therapeutic success of the present case was attributable to the administration of
      IFN-alpha immunotherapy following auto-PBSCT.

PMID- 12053152
TI  - De novo CD5-positive diffuse large B cell lymphoma solely presenting as multiple
      subcutaneous nodules.
AB  - Lymphomas may involve the subcutaneous tissue as a manifestation of generalized
      disease. However, they rarely present with multiple involvement of the
      subcutaneous fat tissue without other sites of the disease. We describe a patient
      with CD5+ diffuse large B cell lymphoma (DLBL) that was confined to the
      subcutaneous tissue. A 74-year-old woman with rheumatoid arthritis was admitted
      because of multiple subcutaneous nodules. The patient had not been treated with
      cytotoxic drugs or methotrexate. The biopsied specimen disclosed diffuse
      infiltration of large cells with a starry sky-like appearance. The cells were
      positive for CD5, CD19, CD20, CD25, IgM, lambda-chain, and negative for CD10,
      CD23 or cyclin D1. Thus a diagnosis of CD5+ DLBL was made. The patient was
      treated with a modified CHOP protocol and complete remission was achieved.

PMID- 12053153
TI  - Danazol therapy for thrombocytopenia in patients with myelodysplastic syndromes.

PMID- 12053154
TI  - Autoimmune thrombocytopenia and neutropenia after autologous peripheral blood
      stem cell transplantation.

PMID- 12053155
TI  - Noise and the PSTH response to current transients: II. Integrate-and-fire model
      with slow recovery and application to motoneuron data.
AB  - A generalized version of the integrate-and-fire model is presented that
      qualitatively reproduces firing rates and membrane trajectories of motoneurons.
      The description is based on the spike-response model and includes three different
      time constants: the passive membrane time constant, a recovery time of the input
      conductance after each spike, and a time constant of the spike afterpotential.
      The effect of stochastic background input on the peristimulus time histogram
      (PSTH) response to spike input is calculated analytically. Model results are
      compared with the experimental data of Poliakov et al. (1996). The linearized
      theory shows that the PSTH response to an input spike is proportional to a
      filtered version of the postsynaptic potential generated by the input spike. The
      shape of the filter depends on the background activity. The full nonlinear theory
      is in close agreement with simulated PSTH data.

PMID- 12053159
TI  - [Proposing surgical management to a patient with low-grade glioma: controversies
      and ethical consequences].
AB  - The therapeutic controversies surrounding low-grade glioma result mainly from the
      lack of certainty about their histological definition, and, from our imperfect
      knowledge of the natural history of the disease. Heterogeneous surgical
      management is the consequence of this situation, which renders difficult to
      propose the best attitude to each individual patient, thus raising ethical
      questions, because the absence of a consensus. Performing prospective studies
      able to analyse these different modalities is mandatory whenever we want to be
      enable to give to our patients the best answer in their precise case, and
      furthermore to justify back our acts too.

PMID- 12053156
TI  - Coarse-grained reduction and analysis of a network model of cortical response: I.
      Drifting grating stimuli.
AB  - We present a reduction of a large-scale network model of visual cortex developed
      by McLaughlin, Shapley, Shelley, and Wielaard. The reduction is from many
      integrate-and-fire neurons to a spatially coarse-grained system for firing rates
      of neuronal subpopulations. It accounts explicitly for spatially varying
      architecture, ordered cortical maps (such as orientation preference) that vary
      regularly across the cortical layer, and disordered cortical maps (such as
      spatial phase preference or stochastic input conductances) that may vary widely
      from cortical neuron to cortical neuron. The result of the reduction is a set of
      nonlinear spatiotemporal integral equations for "phase-averaged" firing rates of
      neuronal subpopulations across the model cortex, derived asymptotically from the
      full model without the addition of any extra phenomological constants. This
      reduced system is used to study the response of the model to drifting grating
      stimuli-where it is shown to be useful for numerical investigations that
      reproduce, at far less computational cost, the salient features of the point
      neuron network and for analytical investigations that unveil cortical mechanisms
      behind the responses observed in the simulations of the large-scale computational
      model. For example, the reduced equations clearly show (1) phase averaging as the
      source of the time-invariance of cortico-cortical conductances, (2) the
      mechanisms in the model for higher firing rates and better orientation
      selectivity of simple cells which are near pinwheel centers, (3) the effects of
      the length-scales of cortico-cortical coupling, and (4) the role of noise in
      improving the contrast invariance of orientation selectivity.

PMID- 12053157
TI  - Computing transient gating charge movement of voltage-dependent ion channels.
AB  - The opening of voltage-gated sodium, potassium, and calcium ion channels has a
      steep relationship with voltage. In response to changes in the transmembrane
      voltage, structural movements of an ion channel that precede channel opening
      generate a capacitative gating current. The net gating charge displacement due to
      membrane depolarization is an index of the voltage sensitivity of the ion channel
      activation process. Understanding the molecular basis of voltage-dependent gating
      of ion channels requires the measurement and computation of the gating charge, Q.
      We derive a simple and accurate semianalytic approach to computing the voltage
      dependence of transient gating charge movement (Q-V relationship) of discrete
      Markov state models of ion channels using matrix methods. This approach allows
      rapid computation of Q-V curves for finite and infinite length step
      depolarizations and is consistent with experimentally measured transient gating
      charge. This computational approach was applied to Shaker potassium channel
      gating, including the impact of inactivating particles on potassium channel
      gating currents.

PMID- 12053160
TI  - [Direct transnasal approach. Description and feasibility in 60 patients].
AB  - BACKGROUND AND PURPOSE: The direct transnasal approach is a less invasive
      approach to the sella turcica and represents an alternative to the sublabial
      transsphenoidal approach with minor oro-nasal complications. In this study, we
      describe this approach with emphasis on post-operative course. METHODS: We
      studied retrospectively 60 patients operated on consecutively by a transnasal
      approach between January 1996 and December 2000. RESULTS: There were 47
      macroadenomas, 9 microadenomas and 4 non-adenomatous pathologies. Despite its
      narrowness, the transnasal approach was possible in all cases and allowed tumor
      removal as satisfactory as with the sublabial approach. Eight patients had
      complications not directly related to the approach: 1 death (meningitis with
      brain stem ischemia), 3 pituitary fossa hematomas, 4 rhinorrheas and 2
      meningitis. Seven patients had complications related to the approach: 2 nasal
      obstructions, 1 nasal dryness, 2 sinusitises and 2 hyposmias. All these local
      complications were transitory and disappeared within 3 months. CONCLUSIONS: In
      our experience, the direct transnasal approach is safe, quick and less invasive
      than the sublabial approach.

PMID- 12053161
TI  - [Heschl's gyrus identification using functional MRI: neurosurgical issue].
AB  - AIM: Localizing Heschl's gyrus with functional MRI (fMRI) is a particularly
      difficult challenge due to the noise of the echo planar sequences and the
      frequent activation of language areas during auditory paradigms. The goal of this
      study was to search for a paradigm capable of assessing only pure primary
      auditory cortex activation with fMRI. MATERIAL AND METHOD: Ten healthy adults
      were studied. Subjects were asked to continuously perform a visual decisional
      task while passively listening to an ON-OFF randomized paradigm of tones and
      rhythmic stimuli. Data were analyzed with SPM. RESULTS: Auditory cortex
      activation was assessed by observing activated pixels in functional images. Due
      to the distraction effect of the visual decisional task, functional images of
      pure primary auditory cortex were obtained in all subjects, with strong and
      selective activation in the Heschl's gyrus. CONCLUSION: This technique, coupled
      with fMRI data of language areas can be used as a preoperative tool for surgical
      preplanning in the left superior temporal region. It shows a clear distinction
      between resectable areas (primary auditory cortex) and not resectable essential
      areas (language areas).

PMID- 12053162
TI  - [Subcranial subfrontal approach for the treatment of extensive cerebrospinal
      fluid leaks].
AB  - BACKGROUND AND PURPOSE: Over the time, the management of cerebrospinal fluid
      (CSF) rhinorrhea has been a major surgical challenge. In this paper, we will
      describe our experience using the extended anterior subcranial approach for the
      repair of extensive or previously treated CSF leaks. This approach consists of a
      nasoorbitofrontal bony flap, then an ethmoidectomy and sphenoidectomy are
      performed and the empty space is filled with subcutaneous fat, a pediculated
      periostal flap is dissected and layed extradurally at the base of the anterior
      cranial fossa. METHODS: Between January 1994 and December 1999, we reviewed the
      charts of 7 men and 3 women with a mean age of 36.5 years. The etiology was
      traumatic in 8 cases. One patient had a spontaneous CSF leak, the other had a
      macroprolactinoma. RESULTS: The average duration of surgery was 5 hours. Patients
      were kept in the Intensive Care unit for an average period of 36 hours. The mean
      follow-up period was 30 months. The success rate was 100%. Postoperatively, all
      of our patients were anosmic, four of them had anosmia as a preoperative finding.
      Cosmetically, the skin incisions are limited to the bicoronal incision.
      CONCLUSION: Knowing that the classical subfrontal and endoscopic approaches have
      their definite indications, our experience with the extended anterior subfrontal
      approach in the treatment of extensive or multiple anterior fossa defects
      suggests that it is a reliable procedure, giving an excellent access with low
      morbidity, provided that the patients are selected properly.

PMID- 12053163
TI  - [Image-guided neuroendoscopy].
AB  - BACKGROUND AND PURPOSE: By definition, image-guided neuroendoscopy is a
      connection between a neuroendoscope and a neuronavigational system creating a
      computer-guided instrument. Our objective was to adapt our rigid endoscope with
      our neuronavigation system to perform computer-guided endoscopy. METHODS AND
      RESULTS: The rigid neuroendoscope, equipped with light emitting diodes, was
      connected to the work station. We report our early results with this device in 17
      patients: 8 ventriculocisternostomies, 5 ventriculocisternostomies with biopsies
      of tumors of the posterior part of the third ventricule, 4 biopsies or tumor
      removal like colloid cysts. No technical complications were encountered.
      CONCLUSIONS: The development of image-guided neuroendoscopy has modified our
      approach to neuroendoscopy because the surgical procedure is facilitated. The use
      of fluoroscopy becomes unnecessary. The surgeon can choose, independent of the
      preestablish surgical technique, the entry point, the target and, of course, the
      optimal trajectory. The technique is adaptable to the individual anatomy of each
      patient, the location and the nature of the target. It is an undeniably useful
      teaching tool and represents a real progress in minimally invasive neurosurgery.

PMID- 12053164
TI  - [Subperiosteal hematoma of the orbit. Three cases].
AB  - Orbital subdural hematoma should be considered in victims of head and face trauma
      with signs of exophthalmia. Early diagnosis and treatment, consisting of
      decompression, is mandatory to avoid long-term functional complications.

PMID- 12053165
TI  - [Subperiosteal hematoma of the orbit associated with subfrontal extradural
      hematoma].
AB  - Subperosteal hematoma is rarely associated with extradural hematoma and orbital
      roof fracture. We report a case observed in a 16-year-old boy who developed
      exophthalmos, diplopia and visual loss after blunt head trauma. Computed
      tomography demonstrated the subperiosteal hematoma associated with a thin
      extradural hematoma and an orbital roof fracture. The hematomas were removed
      during the same procedure via fronto-orbito craniotomy. Surgery led to complete
      recovery without functional sequelae. We stress the importance of early diagnosis
      and treatment of post-traumatic exophthalmos.

PMID- 12053166
TI  - [Frontal sinus osteomas: neuro-ophthalmological complications].
AB  - Osteomas are the most frequent benign tumors of the paranasal sinuses. They often
      grow in the frontal sinus near the nasofrontal duct. They remain frequently
      asymptomatic and they tend to be an incidental finding on radiographic studies.
      Rarely, they extend out of the sinus limits. Two cases with neuro
      ophthalmological complications are reported and discussed. A 19-year-old female
      presented with a progressive left visual impairment and orbital bone deformity. A
      CT-scan revealed a large calcified mass in both frontal sinuses, with left
      intraorbital and frontobasal extension. A 21-year-old man suffered from acute
      frontoethmoidal sinusitis. Radiological exams revealed a right frontal sinus
      osteoma with bilateral nasofrontal ducts obstruction. The frontal sinus cavities
      were filled with a large mucocele with intracranial extension. Both patients were
      successfully treated using frontobasal craniotomy with complete osteoma and
      mucocele removal and cranio facial bone reconstruction. Neuro-ophthalmological or
      intrasinusal complications of osteomas lead to radical treatment. CT-scan and MRI
      analysis for surgical purpose and strategy are emphased.

PMID- 12053167
TI  - [Intracranial primary epidermoid carcinoma].
AB  - We report a case of intracranial primitive epidermoid carcinoma localized in the
      right temporal fossa in a 40-year-old man. The patient was submitted to surgical
      removal of his tumor and radiotherapy. Unfortunately, the survival time was six
      weeks after the operation. Clinical, radiological, anatomopathological features
      and the interest of the radiotherapy are discussed.

PMID- 12053168
TI  - [Primary cauda equina epidermoid cyst. A case report].
AB  - A primary epidermoid cyst of the cauda equina was diagnosed in an eleven-year-old
      boy. The patient had a previous two months history of lumbar pain with unilateral
      L 4 radicular pain. The diagnosis of an epidermoid cyst of the cauda equina,
      suspected by MRI, was confirmed by histology following surgery. Wide tumor
      resection, as complete as possible, was performed with minimum trauma. Presence
      of an epidermoid cyst in the filum terminale is a rare finding, few cases have
      been reported in the literature. However, surgical treatment and favorable post
      operative course are similar to that observed in intraspinal localizations. MRI
      is helpful for the preoperative and differential diagnosis and for post-operative
      follow-up.

PMID- 12053169
TI  - [Dissemination of melanoma cells after anterior surgery of the cervical spine].
AB  - We describe a previously unreported complication after anterior surgery of the
      cervical spine for melanoma. Ten days after the surgical procedure, a 51-year-old
      man presented a huge cystic cervical metastasis along the surgical route. The
      pathophysiology and the surgical risk of the procedure are discussed.

PMID- 12053170
TI  - [Syringomyelobulbia associated with cervical spondylosis. Pathophysiology and
      therapeutic implications].
AB  - Spinal spondylosis is rarely implicated in syringomyelia. We report the case of a
      70-year-old patient with a 10-year history of gait disturbance; constrictive pain
      of lower limbs and urinary incontinance. Physical examination disclosed spastic
      tetraparesis. In the upper limbs, deep tendon reflexes were abolished, with
      hyposthesia and hands amyotrophy. Brain and cervical MRI showed
      syringomyelobulbia with cervical spondylotic myelopathy. Extensive cervical
      laminectomy induced a mild clinical improvement. A second MRI performed 6 months
      after surgery depicted a complete disappearance of the bulbo-medullar cavitation
      with secondary atrophy. Extradural spondylotic compression of the spinal cord
      should be firmly considered as an etiology of syringomyelia. A purely extradural
      decompression could be sufficient to induce regression of the medullary
      cavitation.

PMID- 12053171
TI  - [Primary dural lymphoma. A case report].
AB  - Primary central nervous system lymphoma is an invasive disease in both HIV
      positive and HIV-negative patients. Atypical presentations, including
      leptomeningeal involvement often described in cases with aggressive histology,
      have been reported but primary meningeal B-cell lymphoma appears to be very rare.
      A 40-year-old immunocompetent man developed a voluminous frontoparietal cranial
      vault tumor. The neurology examination demonstrated a large extra-axial mass
      involving the anterior part of the superior longitudinal sinus. The tumor
      extended through the cranial vault, without osteolysis, and grew in the
      subcutaneous tissue. Craniotomy was performed and the entire mass was resected
      without neurological deterioration. Pathology reported B-cell lymphoma. No other
      localization was found. Primary B-cell meningeal lymphoma, as illustrated in this
      case, can be another atypical presentation of CNS lymphoma.

PMID- 12053172
TI  - The spontaneous umbilical perforation of the distal end of ventriculoperitoneal
      shunt.
AB  - We present a case of umbilical perforation of the distal end of
      ventriculoperitoneal shunt as a rare complication of ventriculoperitoneal shunts
      including an umbilical abscess and an infection related with ventriculoperitoneal
      shunt. The ventriculoperitoneal catheter was removed, the umbilical abscess was
      drained and appropriate medication was employed for infection with successful
      outcome. Possible factors that might predispose to these complications of
      ventriculoperitoneal shunting are suggested.

PMID- 12053173
TI  - [Osteosynthesis and fusion of the degenerative spine: results of the SNCLF 2000
      survey of 576 neuro surgeons].

PMID- 12053174
TI  - Mitochondrial death protein Nix is induced in cardiac hypertrophy and triggers
      apoptotic cardiomyopathy.
AB  - Loss of cardiomyocytes through programmed cell death is a key event in the
      development of heart failure, but the inciting molecular mechanisms are largely
      unknown. We used microarray analysis to identify a genetic program for myocardial
      apoptosis in Gq-mediated and pressure-overload cardiac hypertrophy. A critical
      component of this apoptotic program was Nix/Bnip3L. Nix localized to mitochondria
      and caused release of cytochrome c, activation of caspase-3 and apoptotic cell
      death, when expressed in HEK293 fibroblasts. A previously undescribed truncated
      Nix isoform, termed sNix, was not targeted to mitochondria but heterodimerized
      with Nix and protected against Nix-mediated apoptosis. Forced in vivo myocardial
      expression of Nix resulted in apoptotic cardiomyopathy and rapid death.
      Conversely, sNix protected against apoptotic peripartum cardiomyopathy in
      G(alpha)q-overexpressors. Thus, Nix/Bnip3L is upregulated in myocardial
      hypertrophy, and is both necessary and sufficient for Gq-mediated apoptosis of
      cardiomyocytes and resulting hypertrophy decompensation.

PMID- 12053175
TI  - A tumor-homing peptide with a targeting specificity related to lymphatic vessels.
AB  - Blood vessels of tumors carry specific markers that are usually angiogenesis
      related. We previously used phage-displayed peptide libraries in vivo to identify
      peptides that home to tumors through the circulation and that specifically bind
      to the endothelia of tumor blood vessels. Here we devised a phage screening
      procedure that would favor tumor-homing to targets that are accessible to
      circulating phage, but are not blood vessels. Screening on MDA-MB-435 breast
      carcinoma xenografts yielded multiple copies of a phage that displays a cyclic 9
      amino-acid peptide, LyP-1. Homing and binding to tumor-derived cell suspensions
      indicated that LyP-1 also recognizes an osteosarcoma xenograft, and spontaneous
      prostate and breast cancers in transgenic mice, but not two other tumor
      xenografts. Fluorescein-labeled LyP-1 peptide was detected in tumor structures
      that were positive for three lymphatic endothelial markers and negative for three
      blood vessel markers. LyP-1 accumulated in the nuclei of the putative lymphatic
      cells, and in the nuclei of tumor cells. These results suggest that tumor
      lymphatics carry specific markers and that it may be possible to specifically
      target therapies into tumor lymphatics.

PMID- 12053176
TI  - Loss of HIF-2alpha and inhibition of VEGF impair fetal lung maturation, whereas
      treatment with VEGF prevents fatal respiratory distress in premature mice.
AB  - Respiratory distress syndrome (RDS) due to insufficient production of surfactant
      is a common and severe complication of preterm delivery. Here, we report that
      loss of the hypoxia-inducible transcription factor-2alpha (HIF-2alpha) caused
      fatal RDS in neonatal mice due to insufficient surfactant production by alveolar
      type 2 cells. VEGF, a target of HIF-2alpha, regulates fetal lung maturation:
      because VEGF levels in alveolar cells were reduced in HIF-2alpha-deficient
      fetuses; mice with a deficiency of the VEGF(164) and VEGF(188) isoforms or of the
      HIF-binding site in the VEGF promotor died of RDS; intrauterine delivery of anti
      VEGF-receptor-2 antibodies caused RDS and VEGF stimulated production of
      surfactant proteins by cultured type 2 pneumocytes. Intrauterine delivery or
      postnatal intratracheal instillation of VEGF stimulated conversion of glycogen to
      surfactant and protected preterm mice against RDS. The pneumotrophic effect of
      VEGF may have therapeutic potential for lung maturation in preterm infants.

PMID- 12053177
TI  - Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer.
AB  - We have found that EEF1A2, the gene encoding protein elongation factor EEF1A2
      (also known as eEF-1 alpha 2), is amplified in 25% of primary ovarian tumors and
      is highly expressed in approximately 30% of ovarian tumors and established cell
      lines. We have also demonstrated that EEF1A2 has oncogenic properties: it
      enhances focus formation, allows anchorage-independent growth and decreases the
      doubling time of rodent fibroblasts. In addition, EEF1A2 expression made NIH3T3
      fibroblasts tumorigenic and increased the growth rate of ES-2 ovarian carcinoma
      cells xenografted in nude mice. Thus, EEF1A2 and the process of protein
      elongation are likely to be critical in the development of ovarian cancer.

PMID- 12053178
TI  - A high-resolution recombination map of the human genome.
AB  - Determination of recombination rates across the human genome has been constrained
      by the limited resolution and accuracy of existing genetic maps and the draft
      genome sequence. We have genotyped 5,136 microsatellite markers for 146 families,
      with a total of 1,257 meiotic events, to build a high-resolution genetic map
      meant to: (i) improve the genetic order of polymorphic markers; (ii) improve the
      precision of estimates of genetic distances; (iii) correct portions of the
      sequence assembly and SNP map of the human genome; and (iv) build a map of
      recombination rates. Recombination rates are significantly correlated with both
      cytogenetic structures (staining intensity of G bands) and sequence (GC content,
      CpG motifs and poly(A)/poly(T) stretches). Maternal and paternal chromosomes show
      many differences in locations of recombination maxima. We detected systematic
      differences in recombination rates between mothers and between gametes from the
      same mother, suggesting that there is some underlying component determined by
      both genetic and environmental factors that affects maternal recombination rates.

PMID- 12053180
TI  - Dimerization A Key Mechanism of Receptor Tyrosine Kinase Activation.
AB  - Receptor tyrosine kinase superfamily includes a group of growth factor receptors
      with intrinsic tyrosine kinase activity which share similar molecular structure.
      Their ligand-induced activation is mediated primarily by the receptor
      dimerization. It was proposed that ligand-induced homo- or hetero- dimerization
      is essential for the activation of receptor kinase however, the mechanisms of
      receptor dimerization are different. This review introduces the ligand-induced
      dimerization of different receptor tyrosine kinase subclasses and concentrates on
      heterodimerization between members of EGF receptor family, resulting the various
      cellular signaling pathways.

PMID- 12053179
TI  - The Iceland map.

PMID- 12053181
TI  - Mitochondrion and Apoptosis.
AB  - Mitochondrion is not only the major ATP manufacture center of animal cells, but
      also plays a key role, as a main switch, in the regulation of apoptos is. Opening
      of the mitochondrion permeability transition pore (MPTP), the life-or-death
      switch of cells, causes an increase of the permeability of mitochondrial membrane
      and the release of several types of apoptogenic factors from the intermembrane
      space, such as cytochrome c, apoptosis inducing factors (AIFs),procaspases and
      Ca(2+). These apoptotic factors can either activate caspases, the main member of
      apoptotic proteins, or destruct independently the intranuclear chromatin, or
      interact with other Ca(2+) -dependent proteins. These result in structural
      rupture and dysfunction of cells, and the cells are finally degraded into
      apoptotic bodies and died. Studies on the regulation mechanisms of mitochondrion
      in apoptosis will be of great value theoretically as well as potential practical
      usage in designing drugs for cancer, Parkinson's disease and so on, using
      mitochondria as targets. To understand the key role of the mitochondrion in the
      determination of life and death of the cells, recent findings in this field are
      reviewed in this article.

PMID- 12053182
TI  - Non-hydrolytic Disruption of Crystalline Structure of Cellulose by Cellulose
      Binding Domain and Linker Sequence of Cellobiohydrolase I from Penicillium
      janthinellum.
AB  - The cooperation between cellobiohydrolase (CBHI) and endoglucanase (EG) is
      necessary for biodegradation of native cellulose, but its mechanism is still
      poorly understood. The present paper report at the first time that an isolated
      component, the cellulose binding domain with its linker sequence of
      cellobiohydrolase I from Penicillium janthinellum (CBD(CBHI)), plays an important
      role in the synergism between CBHI and EGI during cellulose biodegradation. A
      recombinantplasmid (pUC18C), containing the gene fragment encoding CBD(CBHI) from
      P.janthinellum was derived from pUC18-181. In pUC 18C, the catalytic domain
      region of cbhI gene was deleted by in vitro DNA manipulations and then E.coli JM
      109 was transformed for the production of LacZ-CBD fusion protein. The active
      LacZ-CBD fusion protein was digested by papain and then purified by re-exclusion
      chromatography. The purified peptide sequence of CBD(CBHI) had the ability of
      binding crystalline cellulose. The detailed morphological and structural changes
      of cotton fibers after binding CBD(CBHI) were investigated by using scanning
      electron microscopy, calorimetric activity and X-ray diffraction. The results
      demonstrated that the CBD(CBHI) not only has a high binding capacity to
      cellulose, but also causes non-hydrolytic disruption of crystalline cellulose,
      which leads to the release of short fibers. IR spectroscopy and X-ray diffraction
      show that destabilization is caused by the non-hydrolytic disruption of cellulose
      and the disruption of hydrogen bonds in crystalline cellulose. The efficiency of
      crystalline cellulose degradation was enhanced by synergistic action of CBD(CBHI)
      with EGI. These results suggest that the cellulose-binding domain with its linker
      plays an important role in crystalline cellulose degradation.

PMID- 12053183
TI  - Molecular Cloning of NELIN, a Putative Human Cytoskeleton Regulation Gene.
AB  - For searching cardiovascular-associated genes and investigating their expression
      profiles, human adult heart and aorta cDNA libraries were constructed, and a
      novel gene from adult heart cDNA library was isolated based on large-scale
      ESTs(expressed sequence tags) sequencing(GenBank accession number AF114264). The
      2 736 bp clone contains one 1 344 bp open reading frame extending from 412 to 1
      755. We named it NELIN (nexilin-like protein) because it shares high similarity
      with the rat nexilin. NELIN was expression-restricted in heart, skeletalmuscle,
      artery and vein by Northern blot and RT-PCR analyses, and mapped to chromosome
      1p31-1p32 by database analyses. Based on domain structure, NELIN could regulate
      the formations of stress fibers,focal adhesion and its signaling complex, and
      even participates in the signal transduction in FAs(focal adhesions).

PMID- 12053185
TI  - The Thioredoxin Reductase-deficient E.coli Mutant Enhances Expression into
      Solution of Recombinant Proteins Containing Cys Residues.
AB  - A 3D artificial protein, a salmon calcitonin hexa-polymer, a salmon calcitonin
      octo-polymer and a human prourokinase, was expressed in the cytoplasma of E.coli
      GJ980(trxB(-)) mutant. These recombinant proteins containedcysteine residues of
      different length ranging from 12-22 residues. The mutation was mapped to the gene
      for thioredoxin reductase(trxB) and was found to eliminate the activity of this
      enzyme, which was thought to contribute to the sulfhydryl reducing potential of
      the cytoplasm. Recombinant salmon calcitonin hexapolymer, salmon calcitonin octo
      polymer and human prourokinase had more soluble form in cytoplasm of GJ980
      mutants than in wild-type strain, while 3D-protein, which has nocysteine residue,
      still remain in insoluble form. Results indicate the GJ980(trxB(-)) strain
      allowed the formation of disulphide bonds in the cell cytoplasm which is believed
      to encourage correct folding and soluble expression of the recombinant proteins.

PMID- 12053184
TI  - Hammerhead Ribozymes Suppress HBV(adr) in HepG2 Cells.
AB  - Three hammerhead ribozymes (RS3, RC2 and RC1) targeting to the HBV genome have
      been designed. Plasmids were constructed by inserting the genes of naked and tRNA
      embedded ribozymes into RNA trimming vector pRG523 and then were transferred to
      eukaryotic expression vector. By the similar cloning method the shotgun-type
      plasmids carrying homogeneous RS3 or RtS3 unitconnected in tandem were obtained.
      After co-transfecting the above plasmids and HBV genome containing plasmid into
      human hepatoma cell line HepG2 respectively and selection by G418, the HBV
      inhibiting activity of different kinds of ribozyme in G418-resistant cells was
      achieved by measuring the decrease of HBV-RNA, progeny DNA and the antigens
      expressed. The results showed that all the ribozymes were active with more than
      70% inhibition activity against the HBV and that tRNA-embedded ribozymes had
      higher activity than naked ribozymes. It is worth particular interest that
      shotgun-type ribozymes with the connected unit in tandem with 8 and 12 units
      constructed in the plasmid revealed the highest activity, reaching >90%
      inhibition.

PMID- 12053186
TI  - Enhancement of Macrophage Cytotoxicity by Overexpression of Exogenous NF-IL6
      Gene.
AB  - NF-IL6 (Nuclear factor for IL-6 expression) is involved in inflammatory reaction,
      expression of acute-phase proteins and cytokines, apoptosis and suppression of
      tumor cells, and maintenance of macrophage immunological functions. To
      investigate the role of highly expressed exogenous NF-IL6 in macrophage tumor
      cytotoxicity, a recombinant expression plasmid, pCN, which harbored the coding
      region of NF-IL6, was transfected into murine primary cultured peritoneal
      resident macrophages by an improved DEAE-dextran method. Western blot showed the
      high expression of NF-IL6 in these macrophages. Then the tumor cytotoxicity of
      the NF-IL6-overexpressing macrophages from normal and nude mice was measured by
      an alkaline phosphatase assay, using the human hepatocarcinoma cell line SMMC
      7721 as target cells. Results showed that the overexpression of NF-IL6 enhanced
      the tumor cytotoxicity in both types of macrophages, demonstrating that the
      expression level of the NF-IL6 gene was directly related to the tumoricidal
      activity in these cells.

PMID- 12053187
TI  - Binding of Human Cardiac Myosin Light Chain 1 to Heavy Chain and Actin.
AB  - The cloning and sequence analysis of Chinese human cardiac myosin light chain 1
      (CCMLC1) was previously reported. In this paper the cDNA of CCMLC1 was used as
      template and both of cDNAs of N and C terminal fragments of CCMLC1, each
      containing 98 amino acid residues, were obtained by PCR. Using the expressed
      products of both fragments, the binding experiments of two fragments to
      cardiacmyosin heavy chain of rat, human cardiac actin and to monoclonal antibody
      raised against CCMLC1, have been performed, respectively, by means of
      precipitation with GST-Sepharose beads. The results showed that all the heavy
      chain, actin and monoclonal antibody bound the N terminal fragment of CCMLC1 at
      different sites. Under experimental conditions, the binding of CCMLC1 with actin
      could affect the subsequent binding of CCMLC1 to heavy chain in topologically.

PMID- 12053188
TI  - Complete Nucleotide Sequence and Possible Genomic Expression Strategy of a
      Chinese Isolate of Broad Bean Wilt Virus.
AB  - The complete nucleotide sequence of isolate B935 of the RNAs of broad bean wilt
      virus2 (BBWV2) was determined. RNA1 contained 5956 nucleotide (nt) residues in
      length exclusive the 3' terminal poly(A)tail, and encoded a single long open
      reading frame (ORF) with a molecular weight of 210 063 (210 kD). RNA2 was
      composed of 3 601 nt residues exclusive of the poly(A) at the 3' end, and encoded
      a single long ORF with a molecular weight of 119 002 (119 kD). The determination
      of the N terminal sequences of large coat protein (LCP) and small coat protein
      (SCP) indicated that the polyprotein of RNA2 was cleaved at Q/G(465/466) residues
      and Q/A(867/868) residues, to release three mature proteins a N-terminal protein,
      LCP and SCP. The N-terminal protein shared homology with 58 kD/48 kD movement
      protein of cowpea mosaic virus and contained a similar rNTP-binding domain,
      indicating that this protein may have the function of movement. Comparisons
      between the RNA1-encoded polyprotein and proteins encoded by several species in
      Comoviridae revealed that the 210 kD polyprotein could be cleaved into proteins
      such as RdRp, protease, NTP-binding domain (NTBM), protease co-factor and Vpg.
      The phylogenetic tree based on the amino acid sequences of LCP and SCP confirmed
      that the two serotypes of BBWV should be regarded as different viruses.

PMID- 12053189
TI  - Role of FAK in TNF-alpha/Cycloheximide-induced Apoptosis of SMMC-7721 Cells.
AB  - To explore the role of FAK in TNF-alpha/cycloheximide-induced apoptos is of human
      hepatocellular carcinoma cell line SMMC-7721, the FAK antisense plasmid was
      constructed and transfected into SMMC-7721 cells. Western blot assay was adopted
      to examine PKB level. Flow cytometry assay was used to detect apoptosis. It was
      shown that the SMMC-7721 cells were insensitive to TNF-alpha cytotoxicity, but
      they entered apoptosis quickly in the presence of cycloheximide and TNF-alpha.
      PKB was decreased during TNF-alpha/cycloheximide-induced apoptosis. No
      significant change of PKB level was found in the presence of TNF-alpha or
      cycloheximide, respectively, seeming that PKB level was closely correlated with
      apoptosis. When FAK was 60% reduced as a result of the transfection of SMMC-7721
      cells with FAK antisense construct, the percentage of TNF-alpha/cycloheximide
      induced apoptosis was enhanced at lower dose of TNF-alpha but decreased at higher
      dose of TNF-alpha, compared with the control. Correspondingly, the PKB level in
      FAK-down-regulated transfectants was lower at lower dose of TNF-alpha, but higher
      at higher dose of it. Therefore, FAK regulated TNF-alpha/cycloheximide-induced
      apoptosis in a biphase manner. This function might be related with PKB level.

PMID- 12053190
TI  - Regulation of Gene Expression by SAR of Silkworm Attacus ricini rRNA Gene.
AB  - The 1 kb scaffold-attachment region (SAR) at 5' non-transcription region of rRNA
      gene of silkworm Attacus ricini was cloned into eukaryotic expression vector pLu,
      which contained luciferase report gene and neo(R) selecting marker. After
      transfection of constructs into NIH3T3 cell line by using cation liposome, the
      luciferase activity was monitored to check the SAR's function. The results
      demonstrated that the SAR could enhance gene expression up to 15-fold in stable
      transformed cells, but no obvious gene expression was observed in transient
      transfection. Its effect on gene expression appeared to requirechromosomal
      integration. Southwestern blotting experiments showed that SAR specifically bound
      to nuclear matrix proteins of NIH3T3 cells. The binding with nuclear matrix may
      be necessary for SAR function of transcriptional enhancement.

PMID- 12053191
TI  - Sequence-specific Assignment of (1)H-NMR Resonance and Determination of the
      Secondary Structure of HWTX-II.
AB  - Huwentoxin-II (HWTX-II)is an insecticidal peptide purified from the venom of
      spider Selenocosmia huwena. The structure of this toxin in solution was
      investigated using 2D-NMR. The complete sequence-specific assignments of proton
      resonance in the (1)H-NMR spectra of HWTX-II were obtained by analyzing a series
      of 2D spectrum, including COSY, DQF-COSY, TOCSY and NOESY. All the backbone
      protons and side chain protons, except epsilonNH(2) protons of Lys residues, were
      identified by d(alphaN), d(alpha&dgr);, d(NN) and d(betaN) connectivities. The
      results provide a basis for further determination of the solution conformation of
      HWTX-II. Furthermore the secondary structure of HWTX-II was determined from NMR
      data. It contained mainly extended conformation, especially a double-stranded
      anti-parallel beta-sheet with Trp27--Cys29 and Cys34--Lys36 at the C terminal,
      and it lacked helix. These characters of the secondary structure of HWTX-II were
      similar to those spider toxins which structure in solution had been reported.

PMID- 12053192
TI  - Reconstruction and Analysis of A Human Small Molecular Antibody to Tumor Necrosis
      Factor Alpha.
AB  - A Fab antibody gene was constructed on the basis of the reconstruction of the
      linker of a human anti-TNF-alpha ScFv gene. The two ScFvs before and after
      reconstruction were cloned into expression vector pBV220. About 30 kD recombinant
      proteins were expressed by induction and they constituted 6.5% and 13.8% of the
      total bacterial protein, respectively. A soluble Fab expression vector was
      constructed and transformed into E.coli HB2151.After induction by IPTG, a new
      protein band about 50 kD appeared on SDS-PAGE. The expressed ScFv and Fab were
      purified from E.coli lysates, and further experiments showed that 1) the
      expression amount of reconstructed ScFv was increased distinctly 2) ScFv and Fab
      could bind rhTNF-alpha. The ScFv containing GGGGS had an affinity constant of
      6.70x10(4)(mol/L)(-1), and the ScFv containing (GGGGS) (3) had an affinity
      constant of 7.27x10(5) (mol/L) (-1).The affinity constant of Fab was 7.61x10(5)
      (mol/L) (-1). The Fab and reconstructed ScFv was indifferent in affinity activity
      3) ScFv and Fab neutralized the cytotoxicity of rhTNF-alpha. The neutralizing
      ability of Fab was the same as the reconstructed ScFv, but lower than a mouse
      anti-TNF-alpha mAb. These data may be helpful for using human anti-TNF-alpha
      small molecular Ab in antagonizing the activity of TNF-alpha in therapy.

PMID- 12053193
TI  - Barotolerant E.coli Induced by High Hydrostatic Pressure.
AB  - The barotolerant E.coli TG1P, DH5alphaP, HB101P were obtained from TG1,DH5alpha,
      HB101 after treatment with high hydrostatic pressure, and the survival rates of
      the formers raised 2--3 magnitude, from 1.06x10(-6), 2.98x10(-4), 3.65x10(-3) to
      8.31x10(-3), 3.40x10(-1), 1.69x10(-1),respectively. Comparison of partial
      proteomes of wild and barotolerant bacteria of TG1 and DH5alpha with two
      dimensional electrophoresis showed that three proteins were obviously highly
      expressed in barotolerant bacteria. The N terminal sequence and molecular weight
      of one protein was shown to be V(L)EAGEFFMRA and 21 kD, with high identity to a
      known outmembrane protein in E.coli.

PMID- 12053194
TI  - Recombinant Human DFF45 Inhibits Apoptosis-specific Endonuclease in a Cell-free
      System of Xenopus Egg Extracts.
AB  - The human DNA fragmentation factor (DFF) is a heterodimer of 40 kD and 45 kD
      subunits. The 40 kD subunit (DFF40) has an intrinsic DNase activity responsible
      for the genomic DNA degradation into nucleosomal fragments during apoptosis. As
      an inhibitor for DFF40, the 45 kD subunit (DFF45) complexes with DFF40,
      inhibiting DNase activity until certain apoptosis signals are received. In cells
      undergoing apoptosis, the cleavage of DFF45 by activated caspase-3 frees
      DFF40from the complex and initiates the apoptosis-specific DNA fragmentation. In
      this report, the coding region of human DFF45 gene was amplified from the total
      RNA of HeLa cells by RT-PCR. The resulting 1 kb DNA fragment was cloned into the
      bacterial expression vector pET-28a(+) with a 6xhistidine tag fused to the N
      terminus of DFF45, generating plasmid pET28a-DFF45, which was then used to
      transform E.coli BL21(DE3). Induced by IPTG, the recombinant DFF45 was expressed
      efficiently with a yield of 56.6% of total bacterial proteins. The product was
      purified to homogeneity through a nickel affinity column, followed by heat
      treatment, and approximately 4--6 mg of DFF was purified from 100 ml culture.
      Purified recombinant human DFF45, added into the apoptotic cell-free system of
      Xenopus egg extracts, could effectively inhibit both the digestion of lambdaDNA
      and the degradation of chromosomal DNA into nucleosomal fragments in the nuclei
      of chicken red blood cells. Our results demonstrated the existence of an
      apoptosis-specific endonuclease in this cell-free system, the activity of which
      could be inhibited by recombinant human DFF45.

PMID- 12053195
TI  - High Expression in CHO Cells and Activity of an Anti-P185(erbB2) Mouse/human
      Chimeric Antibody.
AB  - The McAb C25 against human P185(erbB2) specifically inhibits proliferation of
      cancer cells overexpressing P185(erbB2). In order to decrease HAMA response in
      clinical therapy of human cancer using McAb, and to express this antibody
      efficiently in CHO cells, an anti-P185(erbB2) mouse/human chimeric antibody gene
      containing variable region of C25 gene was constructed. The expression vectors
      were constructed using genomic DNA of human IgG1 constant region, and using neo
      and dhfr genes driven by weaker promoters as selectable marker genes. Variable
      region genes of C25 were cloned by RT-PCR. VL and VH genes of C25 were sequenced
      and then inserted, respectively, into the light chain and heavy chain expression
      vectors. The two expression vectors were cotransfected into CHO-dhfr(-) cells
      with LipofectAMINE. The specificity of the chimeric antibody was verified using
      cellular-ELISA and immuno-fluorescence techniques. ELISA and RT-PCR were used
      toconfirm that the chimeric antibody containing both variable region of C25 and
      human constant region. At 72 h post-transfection, the chimeric antibody could be
      detected in supernatant of CHO cells by ELISA assay and the yield was 1 mg/L.
      After the selection by G418, stepwise MTX pressure (1x10(-8) 2.5x10(-7) mol/L)
      culture was carried out, and the yield of the chimeric antibody was increased up
      to 100 mg/L. The chimeric antibody was demonstrated to have the antigen
      specificity to P185(erbB2) and to carry the human antibody constant region by
      cellular-ELISA, immuno-fluorescence assay, indirect-ELISA and RT-PCR. The
      chimeric antibody could inhibit proliferation of SKBR(3) and SKOV(3) cells at the
      same inhibiting rate asMcAb C25. In conclusion, a mouse/human chimeric antibody
      against human P185(erbB2) with potential of usage in clinical therapy of human
      cancer was constructed and highly expressed.

PMID- 12053196
TI  - Preparation and Use of a Monoclonal Antibodyagainst Luffin b.
AB  - Luffin b is one of the most toxic single chain plant ribosome inactivating
      proteins. It has been successfully used to prepare an immunotoxin against human
      melanoma cells. Two strains of hybridomas (1E5 and 2E1) were screened out using
      cell fusion technique which steadily secreted monoclonal antibodies against
      luffin b. These antibodies specifically reacted with luffin b. The affinity
      constants of 1E5 and 2E1 monoclonal antibodies were determined to be 1.1x10(9)
      mol(-1).L and 7.5x10(8) mol(-)1.L, by RIA,respectively. An immunoaffinity gel
      composed with the 1E5 monoclonal antibody and Sepharose 4B was prepared. The
      luffin b was successfully purified by one step immunoaffinity chromatography from
      the crude extract of Luffa cylindrica seeds. An immunoconjugate 1E5-HRP was also
      prepared and it was successfully used in Western blotting for detection of
      recombinant luffin b from E.coli total proteins.

PMID- 12053197
TI  - SCAIF80, a Novel Inhibitor of Angiogenesis, and Its Effect on Tumor Growth.
AB  - A novel inhibitor of angiogenesis named SCAIF80 (shark cartilage-derived
      angiogenesis inhibitory factor) from shark cartilage has been isolated and
      characterized. SDS-PAGE analysis followed by silver staining revealed a single
      band with molecular weight (M(r)) of 80 kD. To determine whether this protein was
      capable of inhibiting angiogensis, it was assayed in endothelial cell (EC)
      proliferation and migration assay. The results showed that SCAIF80 significantly
      suppressed EC proliferation and migration in a dose-dependent manner. In the
      chick chorioallantoic membrane (CAM) assay, SCAIF80 also showed a potent
      inhibitory activity on angiogenesis in vivo. In animal tests, the growth of tumor
      was potently suppressed by SCAIF80 therapy. Lewis lung carcinoma was inhibited by
      93.83 % at a dose of 5 mg/(kg.d). These findings suggest that shark cartilage may
      produce a novel protein with anti-angiogenic and anti-tumor activity.

PMID- 12053198
TI  - Differentially Expressed Gene Profiles of hCR2-transfected Mouse Cells before and
      after EBV Infection and TPA Treatment.
AB  - Mouse Atlas(TM) cDNA Expression Arrays were used to analyze cellular gene
      expression profiles of human complement receptor type II gene (hCR2)-transfected
      mouse cells before and after EBV infection and TPA treatment, followed by
      screening differentially expressed genes with Eagle Eye II Image Analysis System.
      Results indicated that differentially expressed gene prifiles of EBV and TPA
      treated, hCR2-transfected mouse cells was preliminarily established. This study
      laid the basis for further research in relerant fields.

PMID- 12053199
TI  - Altering Fibroin Heavy Chain Gene of Silkworm Bombyx mori by Homologous
      Recombination.
AB  - A gene unit, which encoded fibroin-like peptide, was synthesized and constructed.
      The unit was multimerized to about 2 400 bp using BamHI and BglII at each end of
      the unit, then was fused with gfp reporter gene. The fusion gene, flanked by the
      5'and 3'sequence of the fibroin heavy chain gene of silkworm Bombyx mori, was
      transferred into the eggs of silkworm by electroporation. After the silkworms
      developed and spinned silk, 73 out of about 5 400 cocoons were brighter than
      normal ones under UV light. The protein extracted from the brighter cocoon could
      react with the GFP polyclonal antibodies. Genomic DNA from these silkworms and
      their progenies were analyzed. The integration of gfp gene into genomic DNA of
      silkworm and the occurrence of expected homologous recombination event had been
      proved by Southern hybridization. It was shown that gfp-fibroin like fusion gene
      had integrated into the genomic DNA of silkworm by homologous recombination and
      the phenotype of "brighter cocoon" could be used to select transgenic silkworms.

PMID- 12053200
TI  - Treatment of Parkinson's Disease by Genetically Modified Immortalized
      Fibroblasts.
AB  - Primary rat fibroblast cells were immortalized by genetic modification of SV40
      large T antigen (LT(Ag)) gene and called RFLT. This cell line was non-tumorigenic
      after grafting into nud-mouse and rat. The LT(Ag)gene stopped expression when the
      cells were transplanted in rat striatum, but it resumed the expression ability
      after the transplanted cells were recovered from striatum and cultured in
      vitro.TH gene and GCH gene were transfected into RFLT, respectively, and two
      types of transfected cells, RFLT-TH and RFLT-GCH, were obtained. In mixed culture
      with these two cell lines, DA was detected with HPLC-ECD. Implanting mixture of
      those cells into the striatum of PD rats significantly decreased their rotational
      asymmetry for up to 12 weeks. The expression of TH gene was proved by TH
      immunohistochemical staining in the sections of rat brain. The establishment of
      the genetically modified immortalized cells may play role in the gene therapy of
      PD.

PMID- 12053201
TI  - The Expression of Adenoviral Mediated gfp Reporter Gene in Tumor Cells Induced
      and Regulated by Irradiation.
AB  - In order to establish a radiation inducible gene expression system for cancer
      gene therapy, the promoter sequence of radiation-inducible Egr-1 gene was
      amplified from genomic DNA of BALB/c mouse with PCR method, and linked to gfp
      reporter gene. Then the pEgr-gfp expression cassette was subcloned into an
      adenoviral shuttle plasmid to generate recombinant adenovirus of AdEgr-GFP by
      using a novel, high efficient method of homologous recombination in bacteria.
      After infection with AdEgr-GFP, MM45T.Li tumor cells were exposed to different
      doses of gamma-irradiation from 0 Gy to 15 Gy in vitro. The percentage of GFP
      expression positive cells increased greatly in a dose-dependent manner as
      detected by FACS and Western blot analysis. For in vivo study, AdEgr-GFP were
      injected intratumorally, and tumor site received different doses of local gamma
      irradiation 48 h after injection, and after 8 h the tumor samples were biopsed
      for investigating the GFP expression. Tumor tissue image analysis revealed that
      gamma-irradiation could markedly increase GFP expression in a dose-dependent
      manner as compared with that of non-irradiated control group. Our results
      indicate that the irradiation can effectively control adenoviral-mediated GFP
      expression in tumor cells via Egr-1 promoter, and these data laid basis for
      further gene radiotherapy study.

PMID- 12053202
TI  - A Vaccine to Coxsackievirus Prepared by High Pressure.
AB  - Effects of high hydrostatic pressure on infectious and immune activity of
      coxsackievirus group B (CVB) was described. CVB was completely inactivated at 230
      MPa pressure and -16 degrees. The inactivated viruses remained highly immunogenic
      and induced CVB-specific serum antibody at a concentration as low as 1:1 500. 67%
      mice vaccinated with the pressurized viruses survived the challenge of fatal dose
      of CVB. These results indicated that the pressurized CVB induced immune reactions
      to protect mice from the viruses, and would be a potential vaccine candidate for
      human myocarditis.

PMID- 12053203
TI  - Co-expression of Triosephosphate Isomerase, Fructose-1, 6-bisphosphate Aldolase
      and Fructose-1, 6-bisphosphatase in E.coli.
AB  - To establish a way to control or to decrease the daily increasing concentration
      of atmospheric CO(2), metabolically engineering Cyanobacteria was taken for the
      improvement of its efficiency of photosynthetic CO(2) fixation. As a preliminary
      stage of this study, three genes coding for three important Calvin cycle enzymes,
      i.e. triosephosphate isomerase (TPI), fructose-1, 6-bisphosphate aldolase(FBP
      aldolase),and fructose-1, 6-bisphosphatase(FBPase), respectively, have been
      cloned into one plasmid, pTrcFAT, which is controlled by promoter trc. Successful
      co-transcriptional expression of these three genes resulted inhigh yields of
      these enzymes under the induction of 0.25 mmol/L IPTG. Bioassay showed that the
      expressed enzymes from one liter of culture could directly catalyze DHAP
      conversion into 700 &mgr;mol of fructose-6-phosphate (F-6-P) per one minute.
      Furthermore, in order to introduce the three genes co-expression system into
      Cyanobacteria, a shuttle plasmid between E.coli and Cyanobacteria was constructed
      using plasmid pTrcFAT and a shuttle vector pDC-8, forming ashuttle plasmid pDCFAT
      2 containing a dimer of the three genes co-expression operator. Successful co
      expression in E.coli of pDCFAT-2 with higher full activity has been obtained.
      This shuttle was used to transform of Cyanobacteria Synechococcus sp. PCC 7942,
      and a few positive colonies were obtained.

PMID- 12053204
TI  - Analysis of the Relationship between Globally Regulated Genes and Their
      Chromosomal Genetic Map Loci during Adipogenesis.
AB  - About a third of the expressed genes had expression level dramatically changed
      during adipocyte differentiation. By locating their chromosomal genetic map
      positions, the positional correlation of these differentiation-regulated genes
      with their expression regulation was analyzed. The results indicated that there
      was no chromosomal positional effect in regulating these genes'expression during
      adipocyte differentiation.

PMID- 12053205
TI  - Inhibition of Scavenger Receptor A Expression Treated with PMA by the Inhibitor
      of Tyrosine Protein Kinase Genistein.
AB  - In order to investigate the relationship between scavenger receptor type A and
      cell signal transduction, human U937 macrophages were treated with tyrosine
      protein kinase inhibitor genistein, then the cells were incubated with [(125)I]ox
      LDL or ox-LDL, and the cellular degradation of [(125)I]ox-LDL or binding were
      measured separately. Then the effect of the drug on cell surface expression of SR
      A were measured by means of autoradiography, it was found that genistein could
      reduce cellular SR-A mRNA transcription by RT-PCR. The results indicated that
      genistein could reduce U937 macrophages to bind lipids and reduce SR-A expression
      by suppression of transcription, and could reduce degradation of lipids by U937
      macrophage and accumulation of cholesterol within the cells. It suggests that the
      function of scavenger receptors may be correlated with cell tyrosine protein
      kinase, the mechanism is transcriptional and it also suggests that SR-A may
      participate in the signal transduction directly.

PMID- 12053206
TI  - Phase behavior of the alpha-hydroxyoctanoic acid/Laureth 4/white oil/water system
      and preliminary evaluation of the phase changes during evaporation of its
      emulsion.
AB  - The phase diagram was determined for the alpha-hydroxyoctanoic acid/Laureth
      4/white oil/water system using visual observation with an optical microscope.
      Typical emulsions were evaporated to determine the structural changes. These were
      compared to those predicted from the phase diagram. Small-angle x-ray diffraction
      was used to determine the location of the alpha-hydroxyoctanoic acid in the
      lamellar liquid crystal. The most important result is the fact that irrespective
      of initial composition, the final result was a suspension of solid acid particles
      with dissolved oil and surfactant in a surfactant/oil liquid with only minute
      amounts of solubilized acid.

PMID- 12053207
TI  - Stability estimation of emulsions of isopropyl myristate in mixtures of water and
      glycerol.
AB  - Phase studies were carried out on systems consisting of isopropyl myristate,
      polysorbate 80, glycerol, and water. The stable oil-in-water emulsion regions
      were identified. An influence of the glycerol-to-water ratio on the area of
      existence of stable emulsions was obtained. The Coulter counter technique was
      used to determine the droplet size in oil-in-water emulsions. A decrease in
      average particle size with an increase in glycerol and polysorbate concentration
      was observed 24 hours after the preparation. Rheologically, the emulsions
      displayed Newtonian behavior. Their viscosities increased with increasing
      glycerol and polysorbate concentrations. The influence of glycerol and
      polysorbate concentrations on the cream separation of one-month-old emulsions
      indicated an increase in emulsion stability with the increase in glycerol and
      polysorbate concentrations. The use of a polysorbate 80 concentration of 5% by
      weight can be proposed for stable oil-in-water emulsions of isopropyl myristate
      in glycerol-and-water mixtures.

PMID- 12053208
TI  - Investigation of jewelry powders radiating far-infrared rays and the biological
      effects on human skin.
AB  - Far-infrared rays have certain kinds of effects on the human body, especially on
      skin, blood circulation, and skin cell vitalizing. Some jewelry powders radiate
      far-infrared rays. Jade has powerful far-infrared ray radiation, and tourmaline
      has pyroelectric and piezoelectric properties and radiated far-infrared rays. The
      jewelry powders (fine powdered jade and tourmaline powders) were screened by far
      infrared rays for radiation properties and tested for the effects of far-infrared
      rays on the human skin by temperature observation using an infrared thermal
      analyzer.

PMID- 12053209
TI  - Applications of cyclodextrins in cosmetic products: A review.
AB  - Cyclodextrins are non-toxic cyclic polysaccharides. They form inlusion complexes
      with numerous organic molecules. The physical and chemical properties of the
      guest molecules change due to complex formation. Thus, for example, the stability
      of the complexed molecule against light and oxygen increases and the vapor
      pressure is reduced. The solubility of slightly soluble molecules increases in a
      cyclodextrin complex. All these and further advantages of cyclodextrins and their
      complexes can be used for the formulation of cosmetic products. As a result,
      effects are possible not realizable with common techniques.

PMID- 12053211
TI  - Atrial fibrillation and minimally invasive coronary artery bypass grafting: risk
      factor analysis.
AB  - Atrial fibrillation (AF) is a frequent arrhythmia after conventional coronary
      artery bypass grafting. With the advent of minimally invasive technique for left
      internal mammary artery-left anterior descending coronary artery (LIMA-LAD)
      grafting, we analyzed the incidence and the risk factors of postoperative AF in
      this patient population. This prospective study involves all patients undergoing
      isolated LIMA-LAD grafting with minimally invasive technique between January 1994
      and June 2000. Twenty-four possible risk factors for postoperative AF were
      entered into univariate and multivariate logistic regression analyses.
      Postoperative AF occurred in 21 of the 90 patients (23.3%) analyzed. Double- or
      triple-vessel disease was present in 12/90 patients (13.3%). On univariate
      analysis, right coronary artery disease (p <0.01), age (p = 0.01), and diabetes
      (p = 0.04) were found to be risk factors for AF. On multivariate analysis, right
      coronary artery disease was identified as the sole significant risk factor (p =
      0.02). In this patient population, the incidence of AF after minimally invasive
      coronary artery bypass is in the range of that reported for conventional coronary
      artery bypass grafting. Right coronary artery disease was found to be an
      independent predictor, and this may be related to the fact that in this patient
      population the diseased right coronary artery was not revascularized at the time
      of the surgical procedure. For the same reason, this risk factor may find a
      broader application to noncardiac thoracic surgery.

PMID- 12053213
TI  - Progesterone inhibits chloride transport in human intestinal epithelial cells.
AB  - Several pieces of evidence suggest that female sex hormones may play a role in
      the regulation of electrolyte transport. We therefore hypothesized that female
      sex hormones might impair regulated transcellular chloride transport in human
      intestinal epithelial cells. The T84 cell line was used for electrophysiological
      studies. Changes in transepithelial resistance and short-circuit current (Isc)
      were measured via a dual voltage/current clamp in epithelial monolayers. Short
      circuit current is equivalent to chloride secretion in T84 cells. Forskolin and 8
      Br-cyclic adenosine monophosphate (cAMP) were used to activate cAMP-dependent Cl?
      transport. Ca2+-dependent secretion was stimulated by the receptor-mediated Ca2+
      agonist carbachol. Acute exposure (30 minutes) to either progesterone or
      estradiol did not affect monolayer viability as reflected by transepithelial
      resistance. Moreover, the secretory response to both cAMP and Ca2+ agonists
      remained unaffected. In contrast, long-term exposure (24 hours) to physiological
      concentrations of progesterone (100 nM), but not estradiol, dose-dependently
      reduced the peak Isc induced by the cAMP-agonist forskolin from 125 +/- 2.7 mA.
      cm(2) in the control group to 96 +/- 2.5 mA. cm(2) in monolayers exposed to
      progesterone (n = 6 for each group; p <0.001). When the cAMP-analogue 8-Br-cAMP
      was used, the same behavior was observed (peak Isc = 112 +/- 1.6 mA. cm(2) vs 88
      +/- 1.7 mA. cm(2) for control vs. progesterone-treated monolayers; n = 6 for each
      group; p <0.001). Taken together, our results suggest that progesterone but not
      estradiol inhibits cAMP-stimulated Cl- secretion in intestinal epithelial cells
      at a site distal to cyclic nucleotide generation.

PMID- 12053212
TI  - Risk indicators for varicose veins in forty- to sixty-year-olds in the Tampere
      varicose vein study.
AB  - The objectives of the study were to discover the main determinants for the
      prevalence of varicose veins in a general population, and to assess the
      possibilities for prevention of this common surgical disease. Varicose veins were
      evaluated in three defined cohorts of 3284 men and 3590 women aged 40, 50, and 60
      years by using a validated questionnaire. The response rate was 75% among men and
      86% among women, and varicose veins were determined by self-assessment.
      Increasing age, female sex, childbirths, standing posture at work, higher weight
      or height, and positive family history were significantly associated with
      varicose veins in a univariate analysis. These factors were further taken into a
      multivariate logistic regression analysis, and female gender (adjusted odds
      ratio, OR 2.2), increasing age (OR 2.2-2.8), a reported positive family history
      for varicose veins (OR 4.9), increasing number of births (OR 1.2-2.8), standing
      posture at work (OR 1.6), and higher weight (OR 1.2) and height (OR 1.4) were
      found to independent and significant risk indicators of varicose veins.
      Increasing age, positive family history of varicose veins, and child-births in
      women were the most important factors in terms of population etiologic fractions.
      Familial predisposition and pregnancy-related factors bear important associations
      with varicose veins. Thus prevention of varicose veins appears to be difficult.
      Varicose veins are nonlethal and, therefore, higher age is related to higher
      prevalence.

PMID- 12053214
TI  - Normocalcemia and persistent elevated serum concentrations of 1-84 parathyroid
      hormone after operation for sporadic parathyroid adenoma: evidence of increased
      morbidity from cardiovascular disease.
AB  - Elevated serum concentrations of 1-84 parathyroid hormone (PTH) after operation
      for sporadic parathyroid adenoma have been reported in previous studies, years
      after operation for primary hyperparathyroidism (pHPT). The cause and
      significance of this finding have not been elucidated. Primary
      hyperparathyroidism was diagnosed in 195 patients from January 1987 to December
      1998. Operation for pHPT was performed in 124 patients. To evaluate long-term
      effects of elevated serum 1-84 PTH, biochemical variables and pre- and
      postoperative diseases were investigated from hospital case records. Of the 124
      patients operated on, 103 had a solitary adenoma. Among these patients, 60 had
      normal serum concentrations of 1-84 PTH and calcium postoperatively, 38 patients
      had follow-up for more than 12 months (range 12-207 months-group A). Persistent
      elevated serum concentrations of 1-84 PTH and normocalcemia were found in 23
      patients. Fourteen patients had follow-up for more than 12 months (range 15-76
      months-group B). Two patients had persistent pHPT, and 18 were normocalcemic, but
      in this retrospective study data on serum 1-84 PTH were not available. No
      significant differences were found between groups A and B at the time of
      diagnosis concerning clinical characteristics. More that 12 months after
      operation for pHPT, the patients in group B, with persistent elevated serum
      concentrations of 1-84 PTH, had a significantly (c2 = 11, p = 0.005, and power of
      test 0.66) higher frequency of cardiovascular diseases from ischemic heart
      disease and hypertension. Persistent elevated serum concentrations of 1-84 PTH
      after operation for sporadic parathyroid adenoma may be associated with
      development of cardiovascular disease. This group of patients therefore needs
      lifelong control and, possibly, medical intervention.

PMID- 12053215
TI  - Evaluation of a new composite prosthesis (PL-PU99) for the repair of abdominal
      wall defects in terms of behavior at the peritoneal interface.
AB  - This study was designed to evaluate the behavior of a new composite polypropylene
      polyurethane (PL-PU99) when placed in direct contact with the visceral peritoneum
      during the repair of an abdominal wall defect. Full-thickness abdominal wall
      defects (7 x 5 cm) were created in 36 anaesthetized white New Zealand rabbits.
      The defects were repaired with polypropylene prostheses or PL-PU99 prostheses
      (comprised of PL and a polyurethane sheet glued to the PL with acrylic adhesive)
      to establish two study groups (n = 18 each). Animals were sacrified 14, 30, or 90
      days after implantation and prosthesis/surrounding tissue specimens were
      subjected to light and electron microscopy and morphometric analysis of the newly
      formed peritoneum. Immunohistochemical analysis was performed using the rabbit
      specific monoclonal antibody RAM-11. The biomechanical strength of the implants
      was also assessed. Firm adhesions were detected in the PL implants, whereas
      adhesions were practically non-existent in the PL-PU99 implants. The surface area
      covered by adhesions was greater (p < 0.01) in the PL group (7.36 vs. 0.11 cm2).
      The neoperitoneum formed after the implantation of a PL prosthesis was
      disorganized in structure, whereas that formed at the interface with the PL-PU99
      prosthesis was structurally similar to the host peritoneum. The excellent
      performance of the PL-PU99 prosthesis shown in this study warrants further
      investigation into its use for the repair of abdominal wall defects when the
      prosthetic patch needs to be placed in contact with the intestinal loops.

PMID- 12053216
TI  - Short- and long-term outcome and health-related quality of life after severe
      peritonitis.
AB  - The short-form survey 36 (SF-36) is a useful and qualified instrument for
      measurement of health-related quality of life (HRQL) in critically ill patients.
      In this study we determined hospital mortality, hospital discharge mortality, and
      HRQL of 136 patients with severe peritonitis admitted to our hospital between
      January 1996 and May 1999. Hospital mortality was 46% and hospital discharge
      mortality 10%. The HRQL-questionnaire was answered completely by 97% of the
      patients who where still alive during the study period. Age significantly reduced
      physical functions in these patients. Patients with cancer had significant
      impaired physical functions in the first year, followed by significant impairment
      in emotion. Generally, patients who survived peritonitis and had no malignancy
      had an acceptable outcome when compared to individuals from a large normal
      population. Health-related quality of life measurements in peritonitis patients
      justify the high efforts in the treatment of these patients, but they do not
      provide a useful tool in the outcome prediction for individual patients.

PMID- 12053217
TI  - Impact of the latest TNM classification for gastric cancer: retrospective
      analysis on 94 D2 gastrectomies.
AB  - The aim of this study was to determine whether the latest edition of tumor-node
      metastasis (TNM) classification provides reliable prognostic information. The
      fifth edition of TNM Classification of Malignant Tumors has introduced for
      gastric cancer the numeric count of involved lymph nodes whereas their
      topographic location was considered in earlier editions. For our study, data from
      94 patients who underwent D2-gastrectomy were reviewed. The N-factor was scored
      according to both the Japanese Research Society for Gastric Cancer (JRSGC)
      classification (n) and, retrospectively, the latest TNM classification (N).
      Actuarial survival was calculated for both groups. The two staging systems showed
      similar stratification of actuarial survival with relation to N-stage; in the
      JRSGC classification no statistical differences were observed between n1 and n2
      patients (62.7% vs. 52.5%; p = NS), whereas the 5th TNM classification showed a
      significant difference between N1 and N2 patients (68.5% vs. 45.0%; p = 0.04),
      and between N1 and the new category of N3 patients (68.5% vs. 45.0%, p = 0.03).
      It appears, therefore, that the numeric count of involved nodes may represent a
      more reliable indicator for single-case prognosis. Reclassification of all node
      positive patients in our series caused an overall stage modification in 32.9%
      (31/94); 22 of those patients were reclassified to a less favorable stage
      (23.4%). In addition, 11.7% of patients (6/51) who were previously designated n1
      were reclassified as N2, shifting from an expected actuarial survival after 72
      months of 62.7% to 33.3%.

PMID- 12053218
TI  - Higher morbidity and mortality after combined total gastrectomy and
      pancreaticosplenectomy for gastric cancer.
AB  - Total gastrectomy with pancreaticosplenectomy for gastric cancer has been
      proposed for facilitating lymph node dissection or for resection of direct tumor
      invasion to the pancreas, especially for T4 lesions. Its effectiveness in
      improving patient survival is still controversial, and higher morbidity and
      mortality with this procedure have been reported in several series. Such risks to
      patient survival were not observed in the Japanese series. Based on a prospective
      gastric cancer database maintained from 1987 to 1999 in our institution, the
      morbidity and mortality were analyzed in our series of pancreaticosplenectomies.
      A total of 1,278 patients with gastric cancer received gastrectomy in our
      surgical unit. Of these, 127 patients underwent curative total gastrectomy with
      pancreaticosplenectomy in order to facilitate lymph node dissection or removal of
      direct tumor invasion. Operative time, postoperative hospital stay, postoperative
      complications, and surgical mortality were analyzed. Compared to another 201
      total gastrectomies, longer mean operative time (7.91 +/- 2.16 hours vs. 6.67 +/-
      2.01, p <0.001) and postoperative hospital stay (median, 24.5 days vs. 17, p
      <0.001) for combined organ resection (pancreaticosplenectomy) were shown in this
      series. The major complication rate, including intraabdominal abscess,
      anastomotic leak, postoperative bleeding, pancreatitis/fistula, chylous leak, and
      general complications causing unstable vital signs (26.8% vs. 11.9%, p = 0.001),
      but not the mortality rate (6.3% vs. 4.8%, p = 0.608), was also shown to be
      higher in pancreaticosplenectomy patients. The most frequent fatal complication
      was intraabdominal abscess. However, more than 50% of complications occurred in
      the first 40 pancreaticosplenectomies (1987-1991); after adequate accumulation of
      experience, the total complication rate (57.5% vs. 35.6%, p = 0.021), major
      complication rate (40% vs. 20.7%, p = 0.022), and mortality rate (17.5% vs. 1.1%,
      p = 0.001) improved significantly in the remaining 87 patients (1991-1999). We
      therefore conclude that total gastrectomy with pancreaticosplenectomy can be
      performed by experienced surgeons with acceptable risk of morbidity and
      mortality.

PMID- 12053219
TI  - Inhibitory effect of epigallocatechin-3-gallate on growth and invasion in human
      biliary tract carcinoma cells.
AB  - Based on recent evidence that tea consumption contributes to a decreased
      incidence of human carcinomas, a number of investigators have focused on the
      mechanisms of cancer prevention by tea extracts, especially green tea
      polyphenols. Epigallocatechin-3-gallate (EGCG) is a representative polyphenol
      that inhibits the activity of the cyclin-dependent kinases of cdk2 and cdk4. This
      suggests that EGCG may exert its growth-inhibitory effects through modulation of
      G1 regulatory proteins such as cdk2 and cdk4. The human biliary tract carcinoma
      cells (TGBC-2, SK-ChA-1, and NOZC-1) were treated with different doses of EGCG
      (0, 25, 50, 100, and 200 mM) for 48 hours in cell medium. Cell proliferation was
      analyzed by WST-1 colorimetric assay. For the cell-invasion analysis, the cells
      were incubated with 100 mM of EGCG for 2 hours. The cells were then added into a
      Matrigel-coated Cell Insert. After incubation at 37 degrees C for 24 hours, the
      cells visible through the Matrigel were counted under the microscope. All human
      biliary tract cancer cells studied showed a significant suppression of cell
      growth by EGCG treatment in a dose-dependent manner (27.2%, 16.0%, and 10.1%, in
      TGBC-2, SK-ChA-1, and NOZC-1, respectively, at the dose of 200 mM).
      Epigallocatechin-3-gallate treatment also produced a significant suppression of
      invasive ability of the carcinoma cells (12.6%, 11.2%, 7.9%, in TGBC-2, SK-ChA-1,
      and NOZC-1, respectively, at a dose of 100 mM). These data indicated that EGCG
      might be a potent biological inhibitor of human biliary tract cancers, reducing
      their proliferative and invasive activities.

PMID- 12053220
TI  - Clinicopathological prognostic factors and impact of surgical treatment of mass
      forming intrahepatic cholangiocarcinoma.
AB  - The clinicopathological characteristics relevant to prognosis after surgical
      treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study,
      the clinicopathological features of 19 patients with mass-forming ICC, the most
      common form of the disease, were reviewed to analyze prognostic determinants. Two
      or more segmentectomies of the liver with systematic lymphadenectomy were
      performed in 18 patients. Resection of the extrahepatic bile duct was performed
      in 14 patients, and reconstruction of the portal vein was accomplished in 5
      patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN)
      metastasis was present in 14 patients. The estimated 5-year survival rate after
      surgery for mass-forming ICC was 28%, with median survival time of 18 months. In
      univariate analysis, five variables were determined to be significantly
      correlated with poor survival of patients with mass-forming ICC after surgery.
      These variables include mass-forming ICC with periductal infiltration, perineural
      invasion, portal vein invasion, presence of intrahepatic metastasis, and two or
      more LN metastases. Survival rates of 5 patients without LN metastasis and 6
      patients with a single LN metastasis were 80% and 33% at 5 years, respectively,
      while 8 patients with two or more LN metastasis failed to survive beyond 2 years.
      Multivariate analysis revealed the presence of intrahepatic metastasis to be an
      independent prognostic factor of poor survival. Hepatectomy with resection of the
      extrahepatic bile duct and systematic lymphadenectomy yields a good chance for
      prolonged survival for patients with mass-forming ICC when the lesion is singular
      and LN metastasis is limited to a regional LN. Because the presence of
      intrahepatic metastasis was closely related to a poor prognosis in patients with
      mass-forming ICC, efficacious chemotherapy would be needed to control development
      of the lesion.

PMID- 12053221
TI  - Changes in serum hyaluronic acid levels and expression of CD44 and CD44 mRNA in
      hepatic sinusoidal endothelial cells after major hepatectomy in cirrhotic rats.
AB  - Serum hyaluronic acid (HA) is widely distributed in connective tissues, and the
      majority of circulating HA is degraded by hepatic sinusoidal endothelial cells
      (SECs) via a receptor recycling pathway. Our previous clinical study revealed
      that monitoring serum HA levels after hepatectomy is useful in predicting the
      development of liver failure. In the present study, to determine the mechanism of
      the high HA levels after hepatectomy, especially in patients with liver
      cirrhosis, expression of the major HA receptor, CD44, and its mRNA was
      investigated in SECs isolated from rats with thioacetamide-induced liver
      cirrhosis subjected to 70% hepatectomy (group I) and from rats with a normal
      liver that were subjected to 70% hepatectomy (group II). The 48-hour
      postoperative survival rate in group I (13.3%) was significantly lower than in
      group II (100%). In group II, the expression of CD44 mRNA had increased
      significantly at 6 hours after hepatectomy, and this was followed by progressive
      increases in expression of CD44, indicating activation of SEC function. The
      increased serum HA levels after hepatectomy in group II became normal as CD44
      expression increased. By contrast, the expression of CD44 and CD44 mRNA in group
      I was markedly attenuated after hepatectomy. The very low CD44 expression was
      followed by a significant and sustained increase in serum HA levels, indicating
      functional failure of the SECs. These results suggest that the significantly
      impaired functional reserve of SECs in liver cirrhosis is associated with
      increased mortality after 70% hepatectomy.

PMID- 12053222
TI  - Clinical characteristics of hepatitis B core antibody-positive hepatocellular
      carcinoma.
AB  - The pathology and prognosis of hepatitis B surface antigen (HBsAg)-positive
      hepatocellular carcinoma (HCC) and hepatitis C virus antibody (HCVAb)-positive
      HCC is well documented. However, patients with HBsAg-negative/hepatitis B core
      antibody (HBcAb)-positive HCC are included with non-B non-C disease and have been
      characterized independently. A series of 125 patients who had undergone
      hepatectomy for HCC were divided into three groups and compared. The HBsAg group
      comprised 25 HBsAg-positive patients, the HCV group comprised 70 HCVAb-positive
      patients, and the HBcAb group comprised 22 HBcAb-positive/HBsAg-negative
      patients. Eight patients of negative virus markers were excluded in this study.
      Tumors were larger in the HBcAb group (6.2 cm) than in the HBsAg (4.4 cm) and HCV
      (3.7 cm) groups. Disease-free 1-, 3-, and 5-year survival rates were,
      respectively, 75.0%, 57.1%, and 57.1% in the HBcAb group; 60.9%, 41.8%, and 41.8%
      in the HBsAg group; and 88.0%, 54.0%, and 37.8% in the HCV group. HBcAb-positive
      HCC patients had larger tumors, but their prognosis was relatively good. Although
      HBsAg and HCVAb are used for conventional screening of patients with hepatic
      disorders, we believe that screening is also necessary in patients with positive
      HBcAb titers for early detection of HCC.

PMID- 12053223
TI  - Significance of bile leaks complicating conservative surgery for liver
      hydatidosis.
AB  - Hepatic hydatidosis presents a challenge in liver surgery, and there is still
      controversy regarding the appropriate surgical technique. A high incidence of
      postoperative bile leaks is reported as a significant disadvantage of
      conservative surgical procedures. The purpose of this study was to examine the
      incidence and clinical importance of bile leakage in patients being treated
      exclusively by a conservative surgical technique. From January 1985 to November
      2000 a total of 187 patients were operated on at our department for hepatic
      hydatidosis. They were subjected to the standard conservative surgical technique
      (wide unroofing and cyst drainage). A total of 18 complications were related to
      bile leakage (10%), 3 of them bile abscesses (1 drained surgically and 2
      percutaneously), 1 case of bile peritonitis due to an accessory bile duct in the
      gallbladder bed (treated surgically), and 14 fistulas (1 bronchobiliary and 13
      biliocutaneous). Five of the fistulas, including the bronchobiliary one, were
      treated successfully by endoscopy; and the remaining nine healed after
      conservative treatment. Bile leakage, representing a significant complication
      following conservative operations for hepatic hydatidosis, can be effectively
      treated conservatively or endoscopically, not justifying more aggressive surgical
      approaches.

PMID- 12053224
TI  - Impact of grade of dysplasia in villous adenomas of Vater's papilla.
AB  - Therapeutic strategies for villous adenoma of the papilla of Vater remain
      controversial. This study evaluates the accuracy of preoperative histopathologic
      diagnosis and the impact of the grade of dysplasia on recurrence as well as on
      potential alteration of the surgical approach. A series of 32 patients with an
      adenoma of Vater's papilla who underwent local resection or pylorus-preserving
      pancreaticoduodenectomy between January 1990 and August 2000 were reviewed
      retrospectively. Multiple endoscopic biopsies had been performed preoperatively.
      The histopathology of the preoperatively obtained biopsy specimens and subsequent
      surgical specimens were evaluated for grade of dysplasia by two pathologists and
      correlated with the clinical course after operative treatment. Altogether, 3 of
      11 patients (27%) with a low-grade (LG) dysplasia adenoma and 6 of 21 patients
      (29%) with a high-grade (HG) dysplasia adenoma in the initial endoscopic biopsy
      specimens exhibited invasive carcinoma at the postoperative histologic
      examination (NS). Recurrence was not observed in the 6 patients from the LG
      dysplasia adenoma group following local resection and benign postoperative
      histology. In contrast, recurrence of villous adenoma was discovered in 2 of 12
      patients (17%) and development of invasive carcinoma in 5 of 12 patients (42%)
      from the preoperative HG dysplasia group (p <0.05). The overall risk of carcinoma
      after primary diagnosis of an HG dysplasia adenoma was 44% (14/32). Adenoma of
      the papilla of Vater including HG dysplasia appears to be associated with a high
      risk of exhibiting invasive carcinoma postoperatively and a high rate of
      recurrence. Therefore pylorus-preserving pancreaticoduodenectomy should be
      offered to patients with an HG dysplasia adenoma.

PMID- 12053226
TI  - Minilaparotomy approach to terminal ileal Crohn's disease.
AB  - The feasibility and safety of a minilaparotomy approach to terminal ileal Crohn's
      disease have not been fully elucidated. The purpose of this study was to compare
      early outcomes utilizing this technique as an alternative to conventional
      approaches. Nine patients with terminal ileal Crohn's disease (but no
      complicating enteric fistulas) who underwent minilaparotomy between January 1998
      and September 2000 were studied prospectively. The minilaparotomy approach
      entails a complete surgical procedure performed through a skin incision of less
      than 7 cm. Ten similar patients who underwent conventional laparotomy between
      January 1995 and December 1997 served as the control group. Age, gender, body
      weight, height, body mass index, number of prior laparotomies, operating times,
      operative blood loss, and types of operative procedure were similar for cases and
      controls. The length of the laparotomy incision in the minilaparotomy approach
      group was significantly shorter than that in the conventional approach group
      (median length 6.0 vs. 16.5 cm; p <0.05). Postoperative intervals until initial
      standing and walking were significantly shorter for minilaparotomy patients than
      conventional surgery patients (p <0.05 and p <0.05, respectively), whereas
      postoperative intervals until passing flatus, urinary catheter removal, and
      tolerance of liquids and solids did not differ for the two groups, nor did the
      analgesic requirement or postoperative hospital stay. Postoperative complications
      developed in two conventional-group patients; none was noted with the
      minilaparotomy approach. Our data suggest that the minilaparotomy approach to
      terminal ileal Crohn's disease without an enteric fistula is feasible, safe, and
      less invasive than the conventional approach.

PMID- 12053225
TI  - Pain management of patients with unresectable peripancreatic carcinoma.
AB  - In patients with unresectable peripancreatic carcinoma, pain is generally treated
      with pain medication or with a celiac plexus blockade. Radiotherapy has also been
      reported to reduce pain. The efficacy of these treatment modalities is still
      under discussion. The aim of this study was to analyze the effects of the various
      types of pain management on patients who underwent palliative bypass surgery for
      unresectable peripancreatic carcinoma. During the period January 1995 to December
      1998 a series of 98 patients underwent palliative bypass surgery, mostly for
      unresectable disease found during exploration. Patients were divided into three
      groups: palliative bypass surgery (BP), palliative bypass surgery with an
      intraoperative celiac plexus blockade (CPB), and palliative bypass surgery with
      or without celiac plexus blockade followed by high-dose conformal radiotherapy
      (RT). Radiotherapy was performed only in selected patients with locally advanced
      disease and without metastases, implying a better prognosis of the last group.
      The pain medication consumption, pain medication-free survival, hospital-free
      survival, and overall survival were analyzed. The preoperative consumption of
      pain medication was significantly higher in the CPB group than in the BP or RT
      group. The postoperative consumption of pain medication in the CPB, BP, and RT
      groups increased during follow-up from 15%, 17%, and 13% before surgery to 52%,
      57%, and 46%, respectively, at three-fourths of the survival time (NS). This
      increase in consumption of pain medication was not different in the three groups.
      In the RT group the median pain medication-free survival was significantly longer
      than in the BP or CPB group (9.3 vs. 3.1 and 3.3 months; p = 0.02). The median
      hospital-free survival and median overall survival were significantly longer in
      the RT group than in the CPB group (10.3 vs. 6.8 months, p = 0.01; and 7.1 vs.
      10.8 months, p = 0.01). Celiac plexus blockade as pain management did not result
      in an increase of the pain medication-free survival or overall survival.
      Therefore a positive effect of a celiac plexus blockade on pain could not be
      confirmed in the present study. Radiotherapy resulted in increased pain
      medication survival, hospital-free survival, and overall survival compared to
      celiac plexus blockade. These effects are probably partly related to patient
      selection.

PMID- 12053227
TI  - Metallothionein: early marker in the carcinogenesis of ulcerative colitis
      associated colorectal carcinoma.
AB  - Metallothioneins (MTs) are zinc-binding proteins whose overexpression may lead to
      sequestration of zinc ions and consequently to functional inactivation of the p53
      tumor suppressor gene. The aim of the study was to investigate the potential role
      of MTs in the carcinogenesis of ulcerative colitis (UC) as well as possible
      effects on p53 function. The monoclonal antibodies E9 (anti-MT), DO-7, and 1801
      (anti-p53) and the polyclonal antibody CM-1 (anti-p53) were used to stain
      formalin-fixed, paraffin-embedded colon specimens obtained from 14 patients with
      UC-associated colorectal carcinoma (CAC), 13 with high-grade dysplasia (HGD), 10
      with low-grade dysplasia (LGD), and 30 with UC without dysplasia or carcinoma.
      Statistical significance (p <0.05) was assessed using Fisher's exact test.
      Positive MT staining (> 20% of tumor, dysplastic, or epithelial cells) was found
      in most UC and LGD but in only a small percentage of HGD and CAC (p <0.01 for CAC
      vs. UC and LGD vs. HGD). Positive p53 immunoreactivity was observed predominantly
      in HGD and CAC but not in LGD and UC (p <0.01 for CAC vs. UC and HGD vs. LGD). In
      histologically normal tissue neighboring CAC, significant MT expression was found
      in six of seven specimens with simultaneous lack of p53 expression. MT
      overexpression may represent an important early step in the development of CAC
      independent of p53 expression and should be investigated in the long term as an
      independent cancer risk factor in UC.

PMID- 12053228
TI  - Results of long-term follow-up after curative resection of Dukes A colorectal
      cancer.
AB  - Patients with Dukes A (UICC I) colorectal cancer have a good prognosis after
      curative resection. It is not known, however, if the outcome is significantly
      different for UICC Ia and Ib patients or if patients with reduced risks of
      recurrences can be identified early after surgery. This is of interest, as it
      would permit a more cost-effective, patient-oriented, and tumor stage-oriented
      follow-up program. To study these questions, a prospective follow-up database,
      including 1375 patients after curative resection of colorectal cancer, was
      analyzed. A total of 296 patients with Dukes A colorectal cancer with a median
      follow-up of 44 months were studied. Perioperative and follow-up mortality rates
      were 3% and 14%, respectively. Recurrent disease developed in 10% of Dukes A
      patients after a disease-free interval of 16 months. Significantly more patients
      suffering from pT2 (UICC Ib) cancer had recurrent disease than patients with pT1
      (UICC Ia) cancer (13% vs. 4%; p <0.05). Preoperative CEA levels in patients with
      recurrent disease were significantly higher than in long-term disease-free
      patients (5.3 +/- 1.8 vs. 3.5 +/- 0.6 ng/ml; p <0.05). Curative resection of
      recurrent disease was achieved in 38% of the patients with recurrences (4% of all
      patients). Survival analysis showed significantly better survival in patients
      with Dukes A cancer than in those at higher tumor stages (log rank, <0.0001), and
      only 39% of all Dukes A patients who died during follow-up had recurrent disease.
      Dukes A (UICC Ia and Ib) colorectal cancer was diagnosed in 22% of our patients
      treated for cure, and long-term survival was 86%. There were significantly fewer
      cases of recurrent disease after curative resection of UICC Ia (pT1N0M0) cancer,
      so we propose a novel, less intensive follow-up regimen for these patients,
      leading to a more cost-effective, patient-oriented, and tumor stage-oriented
      follow-up program.

PMID- 12053229
TI  - Parasympathetic extrinsic reflex: role in defecation mechanism.
AB  - The rectum has an intrinsic nervous mechanism represented by the enteric nervous
      plexus (ENP) and an extrinsic one mediated by the parasympathetic nerves. Rectal
      distension evokes the rectoanal inhibitory reflex, which acts through the ENP and
      is considered the main mechanism responsible for defecation. However, the role of
      the parasympathetic innervation compared to the role of the intrinsic mechanism
      of the defecation act has so far not been sufficiently addressed in the
      literature. The current study investigated this point. Twelve dogs were
      anesthetized. The anal and rectal pressures were recorded during rectal balloon
      distension with normal saline in 10 ml increments until the balloon was expelled
      to the exterior. The test was repeated after ENP block with a (phentolamine) and
      b (propranolol) adrenoceptor blocking agents and then after rectal denervation by
      bilateral pelvic ganglionectomy. The rectal balloon was expelled to the exterior
      at rectal balloon distension with 30 to 40 ml. After separate administration of
      phentolamine and propranolol, it was dispelled at a distending volume of 50 to 60
      ml, and after rectal denervation at a volume of 80 to 90 ml. The results were
      reproducible. The balloon expulsion test suggests that the intrinsic defecation
      reflex is weaker than the extrinsic one for inducing defecation, although the two
      reflexes appear to be complementary. The difference between them in inducing
      defecation might be significant to our understanding the defecation act in the
      neurogenic rectum, a point that needs further study.

PMID- 12053231
TI  - Surgical results in patients with hepatitis virus-related hepatocellular
      carcinoma in Taiwan.
AB  - To investigate the surgical results of hepatectomy for hepatocellular carcinoma
      in relation to hepatitis virus status in Taiwan, 252 patients (196 men and 56
      women; March 1992 to August 1998) were reviewed. The patients were divided into
      four groups: 30 patients (11.9%) seronegative for both hepatitis B surface
      antigen (HBsAg) and antihepatitis C antibody (HCVAb) (N-HCC group); 133 patients
      (52.8%) seropositive for HBsAg and seronegative for HCVAb (B-HCC group); 66
      patients (26.2%) seronegative for HBsAg and seropositive for HCVAb (C-HCC group);
      and 23 patients (9.1%) seropositive for both HBsAg and HCVAb (BC-HCC group).
      Patients in group C-HCC were older (p = 0.001) and had a higher incidence of
      diabetes mellitus (p = 0.004). Also, they had a higher indocyanine green
      retention rate at 15 minutes (p = 0.021), longer international normalization
      ratio for the prothrombin time (p = 0.049), and smaller tumor (p = 0.006).
      Postoperative complications and hospital mortality were significantly higher in
      patients in the C-HCC and BC-HCC groups (p = 0.046, 0.021). All patients were
      followed 12 to 76 months after hepatectomy (mean 23.5 +/- 16.3 months). The 1-, 3
      , and 5-year overall cumulative survival rates of the 252 patients in this series
      were 80%, 54.3%, and 34.2%, respectively. The cumulative intrahepatic recurrence
      rates were 46.5%, 64.9%, and 72.9% at 1, 3, and 5 years, respectively. The mean
      disease-free survival time was longest in group C-HCC and shortest in group BC
      HCC (p = 0.020). The overall survival time and cumulative survival rates in the
      four groups were not significantly different (p = 0.146).

PMID- 12053233
TI  - Attempted assassination of Benito Mussolini.

PMID- 12053235
TI  - Quantifying natural resource injuries and ecological service reductions:
      challenges and opportunities.
AB  - The natural resource damage assessment (NRDA) provisions of the Comprehensive
      Environmental Response, Compensation, and Liability Act (CERCLA) and the Oil
      Pollution Act (OPA) are complex and have been difficult to implement. The
      complexity and difficulty in implementation arise both from the assessment
      procedures specified in agency NRDA guidance and from the limited ability of
      ecologists to quantify impacts of hazardous substances on natural resources. This
      paper explores the scientific aspects of NRDA implementation, and discusses
      conceptual and methodological relationships between NRDA and the much broader
      field of ecological risk assessment (ERA). We discuss three critical components
      of the NRDA assessment approach: measuring natural resource injuries and
      reductions in resource services; evaluating causality; and establishing baseline
      conditions. We identify (1) specific approaches drawn from ERA practice that
      could improve each of these components, and (2) research needs and institutional
      changes that may improve the ability of the NRDA process to achieve its stated
      objectives. We recommend the acceleration of the ongoing dialogue among NRDA
      practitioners from the Trustee and PRP communities as a first step toward
      resolving the procedural and technical deficiencies of the NRDA process.

PMID- 12053236
TI  - The role of population projections in environmental management.
AB  - California and other regions in the United States are becoming more populated and
      ethnically diverse, and thus, ecological impacts on the wildland-urban interface
      are a significant policy concern. In a socioeconomic assessment focused on the
      geographic regions surrounding four national forests in southern California,
      population projections are being formulated to assist in the update of forest
      plans. In southern California, the projected trend of explosive population growth
      combined with increased ethnic and racial diversity indicates four challenges for
      environmental management. First, patterns of recreation use on wildlands are
      likely to change, and management of these areas will have to address new needs.
      Second, as land-management agencies face changing constituencies, new methods of
      soliciting public involvement from ethnic and racial groups will be necessary.
      Third, growth in the region is likely to encroach upon wildland areas, affecting
      water, air, open space, and endangered species. Fourth, in order to address all
      these concerns in a climate of declining budgets, resource management agencies
      need to strengthen collaborative relationships with other agencies in the region.
      How environmental managers approach these changes has widespread implications for
      the ecological sustainability of forests in southern California.

PMID- 12053237
TI  - Explaining human settlement patterns in a recreational lake district: Vilas
      County, Wisconsin, USA.
AB  - Lakeshore development in Vilas County, northern Wisconsin (USA) is heterogeneous,
      ranging from lakes that are surrounded by homes and commercial establishments to
      lakes that have no buildings on their shorelines. Development in this
      recreational area has increased, and since the 1960s over half of new homes have
      been built on the lakeshore. We examined building density around lakes in
      relationship to 11 variables, including in-lake, shoreline, and social
      characteristics. Buildings in many parts of northern Wisconsin tend to be
      concentrated around shorelines; in Vilas County 61% of all medium-sized buildings
      (our proxy for residential development) on private land were < or =100 m of a
      lake. The probability of development on a lake was largely related to lake
      surface area, with larger, more accessible lakes showing a higher probability of
      development. Building density along shorelines varied with travel cost, lake
      surface area, presence of wetlands, and extent of public land ownership. Building
      density was greater on larger, more accessible lakes that were surrounded by
      forest (as opposed to wetlands) and public lands. Gaining a more precise
      understanding of human settlement patterns can help direct planning and resource
      protection efforts to lakes most likely to experience future development.

PMID- 12053232
TI  - History of treatment of groin hernia.
AB  - The history of open surgery for groin hernia has gone through many stages of
      development, including the ancient era (ancient times to the fifteenth century),
      the era of the start of herniology (fifteenth to seventeenth centuries), the
      anatomic era (seventeenth to nineteenth centuries), the era of repair under
      tension (nineteenth to mid-twentieth century), and the era of tensionless repair
      (mid-twentieth century to the present). Five principles of modern hernia repair
      developed through these periods of development: antiseptic/aseptic hernia
      operation, high ligation of the sac, tightening of the internal ring,
      reconstruction of the posterior inguinal floor, and tensionless repair.
      Interestingly, many of the initial attempts at laparoscopic hernia repair did not
      adhere to the recognized principles of hernia surgery learned from open surgery.
      It is only when the transabdominal preperitoneal mesh repair and the totally
      extraperitoneal approach, which adhere to the basic principles, are considered
      that the results of laparoscopic hernia repair procedures can improve and the
      recurrence of hernia decrease.

PMID- 12053238
TI  - GIS-based support tool system for decision-making regarding local forest
      protection: illustrations from Orissa, India.
AB  - A support tool system comprising risk and priority analyses was illustrated in a
      geographical information system environment and also tested with data from two
      forest protection areas for comparison of the system output. The system is
      recommended as a management monitoring tool for areas where village forest
      protection at a local level is taking place. The geographical area in the eastern
      part of India is subject to scarcity of forest resources and is representative in
      the context of widespread occurrence of local forest protection. Data used were
      topography, hectares protected, population census, distance to forest and other
      villages, degree of forest regeneration, presence of plantations, age of
      protection, surrounding forest resources, and population mix. Methods used were
      digitizing information for the systems' different layers, analyses of satellite
      information, field work, gathering of local information, and the application of
      five risk/priority analyses: erosion, ecological and institutional
      sustainability, conflict, and degree of dependency. Questions asked were how the
      different analyses should be interpreted and how the system could be kept
      updated. The results show that the system needs resource-demanding and field
      assistance to be kept dynamic. The system is also dependent on the
      interpretations of the analyses. The limits or levels of assistance for forest
      management depend on the resources available. The system illustrates how a tool
      can be utilized for decisions regarding input of resources. It can further be
      very useful in defining and comparing different areas in order to detect areas in
      need of assistance and the type of help needed.

PMID- 12053239
TI  - Montreal's Eco-quartier environmental program: local action and municipal
      management.
AB  - This article assesses the City of Montreal's Eco-quartier program from the
      viewpoint of managing the urban environment and improving living environments. It
      evaluates the actual achievements of the program, looking especially at the
      ability of local communities to take effective action to improve their living
      environments, while under the guidance of the associations mandated to manage the
      program at the local level. Our research concentrated on three main areas: a) the
      development of the City of Montreal's environmental program; b) the effectiveness
      of the Eco-quartiers in carrying out their mandate; c) the actual impacts of the
      program in improving living environments.

PMID- 12053240
TI  - Maintaining volunteer commitment to local watershed initiatives.
AB  - Australia's Landcare program is advanced as a successful international example of
      local watershed groups and governments working together to improve natural
      resource management. One of the aspects considered critical in the success of
      watershed groups is engaging widespread participation. This paper draws on two
      regional surveys that explored burnout, or loss of engagement, among Landcare
      participants in the state of Victoria using the Maslach Burnout Inventory. Survey
      findings indicated that a large proportion of respondents were experiencing high
      burnout in terms of low personal accomplishment and suggested that there was
      potential for burnout to increase. The authors suggest that the expectations of
      watershed groups must be based around a realistic assessment of the capacity for
      volunteer groups to deliver improved environmental and social outcomes.

PMID- 12053241
TI  - Importance of public relations in recycling strategies: principles and case
      studies.
AB  - The separate collection of waste, and especially of recyclables with specific
      collection systems, would not be possible without the involvement of the users.
      Apart from the physical installations such as collection containers, collection
      points, etc., the motivation of the users is an essential component. Motivation
      can be reinforced through public relations work. In addition to the underlying
      technical considerations, this paper describes the difference between
      communication in general and public relations and specifically examines public
      involvement in recycling. Through the use of examples, we look at the targeted
      users and typical media employed. Furthermore, we analyzes the development of
      public involvement. The examples show that public relations for recycling
      strategies relies to a great extent on attitudes, habits, and access to the
      target group. Thus, standardized procedures cannot be developed. For these
      reasons, public relation activities must be planned carefully and professionally
      and include an analysis of the target group, choice of media, and verification of
      success.

PMID- 12053242
TI  - Use of loglinear models to assess factors influencing concern for the natural
      environment.
AB  - Since it is necessary to isolate the most significant factors influencing
      personal concern for the environment, this paper utilizes loglinear models for
      identifying the interactions and interrelationships underlying multidimensional
      environmental survey data. A field study in Guyana conducted face-to-face
      interviews with 1600 citizens. Acquired categorical data were then subjected to
      loglinear modeling techniques to determine what significance the factors
      education, age, residential location, and gender have on personal concern for the
      environment. The loglinear models obtained from the five-dimensional contingency
      table suggest that there is a direct relationship between education and personal
      concern for the environment. Age has an interaction with education, and some
      influence on environmental concern, with younger respondents expressing higher
      concern for the environment than older respondents. Other results from the
      loglinear model demonstrate that residential location and the gender of the
      respondents do not have any statistically significant association with personal
      concern for the environment.

PMID- 12053243
TI  - Testing a GIS model of habitat suitability for a declining grassland bird.
AB  - Demand for information that can be used to manage loggerhead shrikes has recently
      increased because of concern over declining populations and loss of open, non
      forested habitat. A previously-developed habitat model was modified to predict
      shrike habitat quality on Fort Riley Military Reservation (FRMR) in Kansas.
      Shrike habitat suitability indices were calculated based on the amount of
      potential and usable foraging habitat, and the number of potential nesting sites
      within a specified area. Interpretation of high quality digital photographs was
      used to delineate land cover classes, hedgerows and tree counts. These data were
      entered into a geographic information system (GIS) as individual data sets. The
      shrike habitat model was then employed to produce a GIS database predicting low,
      moderate, and high quality shrike habitat throughout the Reservation. Model
      results indicated that 67% of the Reservation was suitable habitat for loggerhead
      shrikes. Although over 80% of FRMR was mapped as grassland, the presence of few
      to several isolated trees or hedgerows was identified as a key factor in modeling
      habitat suitability. The accuracy of the GIS model was 82% in predicting suitable
      (moderate and high quality) loggerhead shrike habitat using an independent set of
      66 recent shrike observations. The number of potential nesting sites and percent
      cover of usable foraging habitat were significantly related to habitat
      suitability of the sites occupied by shrikes.

PMID- 12053244
TI  - Climate- and human-induced woody vegetation changes in Botswana and their
      implications for human adaptation.
AB  - For purposes of suggesting adaptive and policy options regarding the sustained
      use of forestry resources in Botswana, an analysis of the whole countrywide
      satellite data (showing the mean present distribution of vegetation in terms of
      species abundance and over all density) and the projection of vegetation cover
      changes using a simulation approach under different climatic scenarios were
      undertaken. The analysis revealed that changes in vegetation cover types due to
      human and natural causes have taken place since the first vegetation map was
      produced in 1971. In the southwest, the changes appear to be more towards an
      increasing prevalence of thorn trees; in the eastern part of the country where
      widespread bush encroachment is taking place, the higher population density
      suggests more human induced (agrarian-degradation) effects, while in the sparsely
      settled central Kalahari region, changes from tree savanna to shrubs may be
      indicative of the possible influence of climate with the associated effects of
      fires and local adaptations. Projection of future vegetation changes to about
      2050 indicates degeneration of the major vegetation types due to the expected
      drying. Based on the projected changes in vegetation, current adaptive and policy
      arrangements are not adequate and as such a shift from the traditional adaptive
      approaches to community-based types is suggested. Defining forestry management
      units and adopting different management plans for the main vegetation stands that
      are found in Botswana are the major policy options.

PMID- 12053245
TI  - An ecological basis for managing giant sequoia ecosystems.
AB  - A strategy for management of giant sequoia groves is formulated using a
      conceptual framework for ecosystem management recently developed by Region Five
      of the USDA Forest Service. The framework includes physical, biological, and
      social dimensions. Environmental indicators and reference variability for key
      ecosystem elements are discussed in this paper. The selected ecosystem elements
      include: 1) attitudes, beliefs, and values; 2) economics and subsistence; 3)
      stream channel morphology; 4) sediment; 5) water; 6) fire; 7) organic debris; and
      8) vegetation mosaic. Recommendations are made for the attributes of
      environmental indicators that characterize these elements. These elements and
      associated indicators will define and control management activities for the
      protection, preservation, and restoration of national forest giant sequoia
      ecosystems.

PMID- 12053246
TI  - Mushrooms, trees, and money: value estimates of commercial mushrooms and timber
      in the pacific northwest.
AB  - Wild edible mushrooms are harvested in the forests of the Pacific Northwest,
      where both trees and mushrooms grow in the same landscape. Although there has
      been some discussion about the value of trees and mushrooms individually, little
      information exists about the joint production of, and value for, these two forest
      products. Through four case studies, the information needed to determine
      production and value for three wild mushroom species in different forests of the
      Pacific Northwest is described, and present values for several different forest
      management scenarios are presented. The values for timber and for mushrooms are
      site- and species-specific. On the Olympic Peninsula in Washington, timber is
      highly valued and chanterelles are a low-value product by weight; timber has a
      soil expectation value (SEV) 12 to 200 times higher than chanterelles. In south
      central Oregon, timber and American matsutake mushrooms have the potential to
      have about the same SEV. In eastern Oregon, timber is worth 20 to 110 times as
      much as the morels that grow in the forest. Production economics is concerned
      with choices about how much and what to produce with what resources. The choices
      are influenced by changes in technical and economic circumstances. Through our
      description and analysis of the necessary definitions and assumptions to assess
      value in joint production of timber and wild mushrooms, we found that values are
      sensitive to assumptions about changes in forest management, yields for mushrooms
      and trees, and costs.

PMID- 12053248
TI  - Degradation model: a quantitative EIA instrument, acting as a decision support
      system (DSS) for environmental management.
AB  - Environmental assessment of alternative development plans, programs, and policies
      may bring conflict among decision-makers, particularly when some quantitative
      measures for decision-making are needed and where cumulative impacts are
      neglected. Environmental impact assessment (EIA) and environmental economics
      theories, despite their usefulness, are not capable of addressing those issues
      and problems alone. In recent years, the decision support system (DSS) has
      provided some solutions, but mathematical analysis of the system to show the
      internal structure of the problem is not always possible. To addres the above
      shortcomings and ongoing problems of decision-making in Iran, a degradation model
      (DM) was introduced as an instrument of EIA, to act as a DSS for managers. The
      model is a compromise between knowledge-based decision support systems, detailed
      models, digested information models, and the basic theorem of environmental
      economics. In the present study (1996-2000), the model was applied in three
      provinces of Iran, representing three of four biogeographical regions of Iran.
      The study area was divided into a set of grids (100 km(2)). The degradation
      coefficient ( H) was computed for all grids (1333), representing the degree of
      degradation in the grid. It is obvious that the higher the coefficient the more
      area is degraded and less prone to further development, and vice versa. In order
      to provide decision-makers with a set of quantitative measures to observe
      impacted areas (critical and noncritical) for resource allocation and further
      development, the degradation coefficients of all grids were classified into
      categories and criteria, using a fuzzy set theoretic approach. Accordingly, only
      24% of study areas are prone to further development. The degradation model as a
      knowledge-based decision support system has its strengths and weaknesses, but it
      has solved managers' ongoing problems in Iran and it could be used elsewhere.

PMID- 12053247
TI  - Detection of coastal saline land uses with multi-temporal landsat images in
      Shangyu City, china.
AB  - Many coastal regions in China are confronted with pressing problems of scarce
      land resources and heavy population. Over the past 30 years, considerable parts
      of coastal tidelands have been enclosed and reclaimed for agricultural land uses.
      To assess, plan, and implement large-scale reclamation programs, up-to-date and
      reliable information concerning the nature, areal extent, and physical and
      chemical characteristics of coastal saline lands is essential. This paper reports
      a remote sensing approach to detecting coastal saline land uses in Shangyu City,
      China, by using multi-temporal Landsat images. First, with the aid of resolution
      sharpened Landsat-7 ETM+ images and their enhanced linear features, a visual
      interpretation is applied to extract individual dikes. Based on time series
      images and local government records, a spatial zoning procedure is then used to
      define six sub-zones with different historical years of reclamation. It shows
      that a total of 15,668 ha of coastal saline lands were enclosed and reclaimed
      from 1969 to 1996. Second, a modified land-use classification system for the
      study area is prescribed, and both unsupervised and supervised classifiers are
      performed for land-use classifications of grouped sub-zones. Information obtained
      from the spatial zoning, Tasseled Cap transformation and Normalized Difference
      Vegetation Index, is also utilized to facilitate the supervised classification
      process. Finally, a detailed land-use map is produced, with an overall
      classification accuracy of 77.8%. Results show that dominant agricultural land
      uses of sub-zones are changed with historical reclamation years, from saline
      lands with wildgrass (very recently reclaimed) to aqua-farm ponds, to cotton
      fields, and to paddy fields and orchards (very early reclaimed). This transform
      process is primarily affected by soil salinities, and according to a soil survey
      an electrical conductivity of saturation extract decreased from 7.3 ds/m in the
      saline land reclaimed in 1996 to below 2 ds/m in the land reclaimed before 1969.
      The study concludes that multi-temporal remotely sensed images are important and
      effective data sources for monitoring the rapid changes of coastal land uses.

PMID- 12053249
TI  - Determination of heavy metals in the bones and livers of deceased neonatal
      humans.

PMID- 12053250
TI  - Lead in blood and hair of shipyard workers, Sabah, Malaysia.

PMID- 12053251
TI  - Toxic elements in marine products and human hair samples in Mersin, Turkey.

PMID- 12053252
TI  - Relationship between age and levels of organochlorine contaminants in human serum
      of a belgian population.

PMID- 12053253
TI  - Determination of organochlorine pesticides in human adipose tissue in Minsk,
      Republic of Belarus.

PMID- 12053254
TI  - Simple solid dose bioassay for insecticides using the fruit fly ( Drosophila
      melanogaster).

PMID- 12053256
TI  - Monitoring of pesticide residues in different sources of drinking water of
      Jaipur, India.

PMID- 12053255
TI  - Comparison of binding energies of selected environmental xenobiotics by porphyrin
      complexes.

PMID- 12053257
TI  - Evaluation of residues of beta-cyfluthrin on cotton.

PMID- 12053258
TI  - Diazinon and its degradation products in agricultural water courses in British
      Columbia, Canada.

PMID- 12053259
TI  - Biodegradation of polycyclic aromatic hydrocarbons by inoculated microorganisms
      in soil.

PMID- 12053260
TI  - Potential of alfalfa plant to phytoremediate individually contaminated
      montmorillonite-soils with cadmium(II), chromium(VI), copper (II), nickel(II),
      and zinc(II).

PMID- 12053261
TI  - Aquatic macrophytes as biomonitors of pollution by textile industry.

PMID- 12053262
TI  - Toxicity of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) to soil
      microbes.

PMID- 12053263
TI  - Acute toxicity of Bunker A and C refined oils to the marine harpacticoid copepod
      Tigriopus japonicus mori.

PMID- 12053264
TI  - Quantitative structure-biodegradability relationships of substituted benzenes and
      their biodegradability in river water.

PMID- 12053265
TI  - Field application of a lysosomal assay as biomarker of copper oxychloride
      exposure, in the snail Helix aspersa.

PMID- 12053266
TI  - Comparison of liquid-liquid extraction (LLE), solid-phase extraction (SPE), and
      solid-phase microextraction (SPME) for pyrethroid pesticides analysis from
      enriched river water.

PMID- 12053267
TI  - Monitoring the impact of the Aznalcollar mining spill on recent sediments from
      the Guadalquivir estuary, southwest Spain.

PMID- 12053268
TI  - Selenium concentration in compartments of aquatic ecosystems in central Chile.

PMID- 12053269
TI  - Glutathione S-transferase activity in mussels, Mytilus edulis, exposed to
      discharges from an aluminum smelter.

PMID- 12053270
TI  - FIV and neuroAIDS.

PMID- 12053271
TI  - Central nervous system infections in individuals with HIV-1 infection.
AB  - Opportunistic infections of the central nervous system (CNS) are common
      complications of advanced immunodeficiency in individuals with human
      immunodeficiency virus type 1 (HIV-1) infection. Neurological disease is the
      first manifestation of acquired immunodeficiency syndrome (AIDS) in 10% to 20% of
      symptomatic HIV-1 infection. Prompt diagnosis and treatment of such disorders is
      critical. Also, in the era of highly active antiretroviral therapy (HAART), these
      disease states have changed in presentation and epidemiology. Therefore, we
      review the epidemiology, pathogenesis, clinical features, diagnosis, and
      management of five common central nervous system disorders in individuals with
      HIV-1 infection: toxoplasma encephalitis, primary central nervous system
      lymphoma, cryptococcal meningitis, cytomegalovirus encephalitis, and progressive
      multifocal leukoencephalopathy.

PMID- 12053272
TI  - Upregulation of chemokine receptor gene expression in brains of Borna disease
      virus (BDV)-infected rats in the absence and presence of inflammation.
AB  - Infection of adult rats with Borna disease virus (BDV) causes CD8 T cell-mediated
      meningoencephalitis. Previously, we described a complex pattern of chemokine gene
      expression in the central nervous system (CNS) of such rats. We now found that
      expression of chemokine receptor genes CXCR3, CCR5, CX(3)CR1, and CXCR4 was also
      upregulated, which is in agreement with the predominance in brains of adult
      infected rats of T cells and monocytes/macrophages that express these receptors.
      In contrast to these rats, neonatally infected rats (designated PTI-NB) develop a
      persistent CNS infection associated with neurodegenerative processes in the
      absence of inflammation. In brains of PTI-NB rats, sustained expression of
      chemokines also takes place. We therefore analyzed mRNA expression of selected
      chemokine receptor genes, as well as of the chemokine fractalkine in brains of
      PTI-NB rats. We observed a marked increase of CCR5 and CX(3)CR1 transcripts in
      brains of these rats. CX(3)CR1 expressing cells were predominantly microglia, and
      upregulation of CX(3)CR1 was mainly due to an increase in the number of CX(3)CR1
      expressing microglia. Fractalkine gene expression was found to be reduced to
      similar extents in brains of adult and newborn infected rats. These findings
      might be of relevance with respect to the selective neuronal cell loss observed
      in brains of PTI-NB rats.

PMID- 12053274
TI  - Simian varicella virus DNA is present and transcribed months after experimental
      infection of adult African green monkeys.
AB  - To study the pathogenesis of simian varicella virus (SVV) infection in its
      natural primate host, we inoculated adult SVV-seronegative African green monkeys
      intratracheally with 10(3)-10(4) PFU of SVV, sacrificed them 11 days, 2, 5, 10,
      and 12 months postinfection (p.i.), and examined lung, liver, and ganglia for SVV
      DNA and RNA. PCR analysis revealed SVV DNA in ganglia and viscera at 11 days and
      2, 5, and 10 months p.i. Similarly, SVV transcripts corresponding to immediate
      early (IE), putative early (E), and late (L) SVV open-reading frames (ORFs) were
      found in liver, lung, and ganglia of most monkeys at multiple intervals for the
      12-month study period. SVV-specific antigens were detected in ganglia and liver
      during acute varicella, but not in ganglia 12 months p.i. Analysis of control
      tissue (ganglia, lung, and liver) from uninfected SVV-seronegative adult African
      green monkeys did not reveal SVV DNA, SVV RNA, SVV-specific antigen, or varicella
      specific pathological changes. Overall, intratracheal inoculation of SVV in
      African green monkeys resulted in the presence of viral DNA and transcription of
      multiple viral genes in many tissues for months after experimental infection.

PMID- 12053273
TI  - Brain resistance to HSV-1 encephalitis in a mouse model.
AB  - Brain resistance to intracerebral superinfections develops after a peripheral
      inoculation of neurovirulent viruses. Superinfection resistance combines
      specificity, toward the virus used for the peripheral inoculum, and short-term
      duration after the inoculum. In order to study this unusual combination,
      neurovirulent superinfections were made on albino Swiss mice previously infected
      with a nasal inoculum. A herpesvirus strain SC16, or a homologue recombinant
      virus carrying the reporter lac Z gene or a vesicular stomatitis virus (VSV) (a
      virus taxonomically unrelated to Herpesviridae) were used. The mice underwent a
      neurological examination and their survival rate was recorded. The brains
      superinfected with the reporter virus were stained for the beta-galactosidase
      reaction to trace the virus spread and the inflammatory infiltrates were
      characterized immunocytochemically. The results confirm and extend previous
      observations about virus specificity and short-term duration of superinfection
      resistance. They show, moreover, an enhanced brain inflammation with T-cells and
      macrophages infiltrating the tissue around microvessels, at a time when both
      neurovirulence and the spread of herpesvirus in the brain are reduced. The
      results suggest that the immune response to superinfection in the nervous tissue
      is enhanced by blood-brain barrier mechanisms that promote the timely
      extravasation of immune cells.

PMID- 12053275
TI  - The relationship of herpes simplex virus latency associated transcript expression
      to genome copy number: a quantitative study using laser capture microdissection.
AB  - To investigate the quantitative relationship of latent herpes simplex virus (HSV)
      genomes to the expression of latency associated transcripts (LATs) we used a
      combination of laser capture microdissection (LCM), polymerase chain reaction
      (PCR), and quantitative real-time PCR to determine the number of HSV genomes in
      individual neurons of the mouse trigeminal ganglion (TG) during viral latency.
      Both LAT-positive and LAT-negative neurons detected by in situ hybridization
      (ISH) and lifted by LCM contained HSV genomes detected by PCR for HSV ICP47. The
      number of genomes/cell determined by real-time PCR with probes for HSV UL44
      following LCM demonstrated a Poisson distribution with a predicted mean count of
      178 genomes/LAT-positive neuron, and 68 genomes/LAT-negative neuron. The range
      was similar between the LAT-positive and LAT-negative neurons, and there was a
      substantial overlap in the distributions. These results suggest that the
      expression of LATs in an amount that is detectable by ISH does not depend only on
      the number of HSV genomes in the cell, and by implication suggests that neuron
      specific factors play a role in the regulation of LAT expression during latency.

PMID- 12053276
TI  - Infection of the choroid plexus by feline immunodeficiency virus.
AB  - The human, simian, and feline immunodeficiency viruses rapidly penetrate into the
      brain and trigger an inflammatory process that can lead to significant neurologic
      disease. However, the mechanisms that permit efficient trafficking of macrophage
      tropic and the more neurotoxic lymphocytotropic isolates are still poorly
      understood. One potential source of virus entry may be the blood-CSF barrier
      provided by the choroid plexus. Infected cells are often detected within the
      choroid plexus but it is unclear whether this reflects trafficking cells or
      infection of the large macrophage population within the choroidal stroma. To
      address this issue, we cultured fetal feline choroid plexus and evaluated the
      ability of feline immunodeficiency virus (FIV) to establish a primary infection.
      Significant provirus was detected in macrophage-enriched choroid plexus cultures
      as well as in the choroid plexus of cats infected in vivo. FIV p24 antigen
      production in vitro was very low but detectable. Addition of a feline T-cell line
      to macrophages inoculated with FIV resulted in a dense clustering of the T cells
      over macrophages with dendritic cell-like morphologies and a robust productive
      infection. The direct infection of choroid plexus macrophages with FIV, the
      efficient transfer of the infection to T cells indicate that the choroid plexus
      can be a highly efficient site of viral infection and perhaps trafficking of both
      macrophage-tropic and T-cell-tropic viruses into the CNS.

PMID- 12053277
TI  - Choroid plexus macrophages proliferate and release toxic factors in response to
      feline immunodeficiency virus.
AB  - Recent observations have suggested that lentiviruses stimulate the proliferation
      and activation of microglia. A similar effect within the dense macrophage
      population of the choroid plexus could have significant implications for
      trafficking of virus and inflammatory cells into the brain. To explore this
      possibility, we cultured fetal feline macrophages and examined their response to
      feline immunodeficiency virus (FIV) or the T-cell-derived protein, recombinant
      human CD40-ligand trimer (rhuCD40-L). The rhCD40-L was the most potent stimulus
      for macrophage proliferation, often inducing a dramatic increase in macrophage
      density. Exposure to FIV resulted in a small increase in the number of
      macrophages and macrophage nuclei labeled with bromodeoxyuridine. The increase in
      macrophage density after FIV infection also correlated with an increase in
      neurotoxic activity of the macrophage-conditioned medium. Starting at 16-18 weeks
      postinfection, well after the peak of viremia, a similar toxic activity was
      detected in cerebrospinal fluid (CSF) from FIV-infected cats. Toxicity in the CSF
      increased over time and was paralleled by strong CD18 staining of
      macrophages/microglia in the choroid plexus and adjacent parenchyma. These
      results suggest that lentiviral infection of the choroid plexus can induce a
      toxic inflammatory response that is fueled by local macrophage proliferation.
      Together with the observation of increasing toxic activity in the CSF and
      increased CD18 staining in vivo, these observations suggest that choroid plexus
      macrophages may contribute to an inflammatory cascade in the brain that
      progresses independently of systemic and CSF viral load.

PMID- 12053278
TI  - Methamphetamine enhances cell-associated feline immunodeficiency virus
      replication in astrocytes.
AB  - Human immunodeficiency virus (HIV) infection among substance abusers is on the
      rise worldwide. Psychostimulants, and in particular methamphetamine (METH), have
      detrimental effects on the immune system as well as causing a progressive
      neurodegeneration, similar to HIV infection. Many Lentivirinae, including feline
      immunodeficiency virus (FIV), penetrate into the central nervous system early in
      the course of infection with astrocytes serving as a reservoir of chronic brain
      infection. We demonstrate that the FIV-Maryland isolate infects feline primary
      and cell line (G355-5)-cultured astrocytes only under cell-associated conditions.
      Infected astrocytes yielded a new astrocytotropic isolate, capable of cell-free
      infection (termed FIV-MD-A). This isolate contained four amino acid substitutions
      in the envelope polyprotein resulting in a change in net charge as compared to
      FIV-MD. Infection for both isolates was dependent upon a functional astrocyte
      CXCR4 receptor. Methamphetamine increased significantly FIV replication in feline
      astrocytes for cell-associated infection only, with no effect on peripheral blood
      mononuclear cells or astrocytes infected with FIV-MD-A. This viral replication
      was related to proviral copy number, suggesting the effect of METH is at the
      viral entry or integration into host genome levels, but not at the translational
      level. Thus, lentiviral infection of the brain in the presence of the
      psychostimulant METH may result in enhanced astrocyte viral replication,
      producing a more rapid and increased brain viral load.

PMID- 12053279
TI  - Increased detection of serum HHV-6 DNA sequences during multiple sclerosis (MS)
      exacerbations and correlation with parameters of MS disease progression.
AB  - In recent years, human herpesvirus 6 (HHV-6) has been investigated as a possible
      causative agent for MS. To determine if the detection of HHV-6 DNA in the serum
      of MS patients correlates with clinical parameters of MS disease progression, a
      total of 215 serum samples was obtained from 59 MS patients followed
      prospectively for a 5-month period. These samples were analyzed for the presence
      of HHV-6 DNA by nested PCR and compared in parallel to MS disease activity. HHV-6
      DNA was amplified in 22% (4/18) of samples obtained during a period of clinical
      exacerbation. Significantly fewer (P = 0.008) sera, 5.6% (11/197), obtained from
      MS patients during clinical remission tested positive for the presence of HHV-6
      DNA. This work demonstrates that the detection of serum HHV-6 DNA is
      significantly correlated with clinical exacerbations in MS. Moreover, the
      findings presented in this study have confirmed previous reports supporting an
      association between MS and HHV-6 and suggest a role for this human herpesvirus in
      the pathogenesis of MS.

PMID- 12053282
TI  - [Long term compliance with an oral protrusive appliance in patients with
      obstructive sleep apnoea].
AB  - BACKGROUND AND OBJECTIVE: Oral protrusive devices (OPD) are increasingly used in
      primary snoring and mild-to-moderate obstructive sleep disordered breathing. Due
      to evidence of reduced compliance with the well established standard treatment of
      nasal positive airway pressure (CPAP) and reports of patient preference for OPD
      treatment, particularly in mild cases, OPD may be considered another treatment
      alternative. PATIENTS AND METHODS: We contacted 192 patients suffering from
      obstructive sleep breathing disorder, who were treated between May 1996 and
      September 2001 with an OPD. The patients" use of the device was evaluated, as
      were any reasons for ceasing to use the device. RESULTS: 105 patients (54.4%)
      regularly used the appliance after a mean time of 22.7 12.3 month. 21 patients
      (10.9%) showed no primary compliance and stopped had using the device before the
      first somnographic follow-up after a mean time of 3.8 months. In this
      investigation 76 patients (80,2%) were classified as responders and 19 patients
      (20.8%) as primary non-responders. 22 responders (11.4%) demonstrated no
      secondary compliance after a mean of 21.9 8.8 months and the discontinued OPD
      treatment themselves. In 21 patients (10.9%) the nightly respiratory parameters
      decreased after a mean of 23.0 11.7 months; hence, those patients required CPAP.
      The cumulative risk using the device after four years as prescribed was 32.2%. We
      found a correlation between patient compliance, body-mass index and the amount of
      teeth in the upper and lower jaws. CONCLUSION: OPD compliance seems to be lower
      than frequently expected. Regular follow-up investigations are necessary to
      ensure adequate treatment. Poor dental status and an excess body-mass index
      reduce patient compliance.

PMID- 12053280
TI  - Neither B cells nor T cells are required for CNS demyelination in mice
      persistently infected with MHV-A59.
AB  - Murine hepatitis virus A59 infection of the central nervous system (CNS) results
      in CNS demyelination in susceptible strains of mice. In infected B-cell-deficient
      mice, demyelination not only occurred but was also more severe than in parental
      C57BL/6 animals. This increase may be due to the persistence of virus in the CNS
      in the absence of B cells. In mice lacking antibody receptors or complement
      pathway activity, virus did not persist yet demyelination was similar to parental
      mice. In infected RAG1(-/-) mice, moderately sized, typical demyelinating lesions
      were identified. Therefore, demyelination can occur in the absence of B and T
      cells.

PMID- 12053283
TI  - [Resistance to thyroid hormone - goiter and attention deficit-hyperactivity
      disorder as main manifestation].
AB  - HISTORY AND CLINICAL FINDINGS: Two siblings with goiter and attention deficit
      hyperactivity disorder were presented. Earlier laboratory tests showed increased
      serum levels of thyroid hormones in association with non-suppressed serum levels
      of thyrotropin (TSH) in both children. Because hyperthyroidism caused by
      inappropriate secretion of thyrotropin was suspected, a cerebral MRI was
      performed. A pituitary adenoma was excluded in both children. Before antithyroid
      drug treatment was initiated, both patients were referred to our hospital.
      Careful medical history, clinical examination of the patients and careful
      interpretation of the laboratory results finally led to the diagnosis resistance
      to thyroid hormone (RTH). INVESTIGATIONS: Thyroid hormone serum levels were
      elevated in both children, while serum TSH was within the normal range. Molecular
      analysis confirmed the diagnosis of RTH. COURSE: Thyrostatic treatment was not
      initiated. CONCLUSION: Careful medical history, correct interpretation of
      laboratory results, comprehensive clinical examination and molecular genetic
      analysis are important in the diagnosis of RTH.

PMID- 12053284
TI  - [Coronary interventions in old patients presenting with cardiogenic shock].
AB  - HISTORY AND CLINICAL FINDINGS: A 80-year-old unconscious woman was admitted to
      our hospital. She had suffered from angina pectoris and progressive dyspnea for
      three days. She had been in pulmonary edema 6 months ago. Clinical examination
      revealed low blood pressure of 90/60 mmHg, central cyanosis and signs of
      pulmonary congestion. INVESTIGATIONS: Laboratory findings comprised elevated
      creatinkinase, troponin and lactate dehydrogenase as well as reduced sodium.
      CLINICAL COURSE: After intubation and mechanical ventilation the patient
      underwent cardiac catheterization because of the cardiogenic shock. Coronary
      angiography revealed severe coronary artery disease with high grade stenoses of
      the right coronary artery and of the main stem of the left coronary artery. After
      initiating intraaortic balloon counterpulsation, transcatheter revascularization
      of the right and left coronary artery was performed, leading to an improvement of
      the systolic left ventricular function. But the patient finally died due to
      cardiac pump failure. CONCLUSION: Elderly patients presenting with cardiogenic
      shock and additional risk factors have the highest mortality. Thus the decision
      for cardiac catheterization and eventual intervention should be made on a case-by
      case basis. Successful angioplasty may reduce mortality by approximately 20 %.
      Due to the usually severe comorbidity absolute mortality is nevertheless very
      high.

PMID- 12053285
TI  - [Colorectal cancer and inhibition of cyclooxygenase-2].

PMID- 12053286
TI  - [Growth hormone and dilated cardiomyopathy].

PMID- 12053287
TI  - [Diagnosis of myocardial infarction and myocardial viability using contrast
      enhanced magnetic resonance imaging].

PMID- 12053288
TI  - [Tumor risk in Peutz-Jegher's syndrome].

PMID- 12053290
TI  - [Immunotherapy in broad allergy spectrum].

PMID- 12053291
TI  - [Is MRI reliable for screening for hepatocellular carcinoma?].

PMID- 12053289
TI  - [In fibromyalgia antibiotic therapy is not indicated].

PMID- 12053292
TI  - [Influence of hemoglobin value on hematogenous tumor cell dissemination at the
      time of primary breast carcinoma diagnosis].

PMID- 12053293
TI  - [Colorectal carcinoma].

PMID- 12053295
TI  - Conscious sedation with intermittent midazolam and fentanyl in electrophysiology
      procedures.
AB  - OBJECTIVES: To determine the safety and efficacy of intermittent midazolam and
      fentanyl conscious sedation for electrophysiology procedures (EP). BACKGROUND:
      Intermittent midazolam and fentanyl conscious sedation was administered in 700
      consecutive cases (175 radiofrequency ablations, 163 EP studies, 261 pacemakers,
      and 101 implantable cardioverter-defibrillators) for 471 patients (239 males,
      51%) mean age 65 +/- 15 years. The mean dose of midazolam was 0.063 mg/kg/hr and
      fentanyl was 0.591 microgram/kg/hr. METHODS: Cardiac rate and rhythm were
      monitored continuously, while blood pressure and arterial oxygen saturation were
      noninvasively assessed every 5 minutes. Drugs were administered in aliquots of
      0.5 to 2.0 mg of midazolam and 6.25 to 25 micrograms of fentanyl as determined by
      clinical condition every 15 to 30 minutes. RESULTS: There were no deaths. In no
      case was endotracheal intubation required. Mild hypoxemia (SaO2 > 80%, but < 90%)
      occurred in 17 cases (2.4%) and was easily reversed with verbal stimulation and
      oropharyngeal repositioning (12 cases, 1.7%), increased F1O2 (3 cases, 0.4%), or
      intravenous naloxone (2 cases, 0.3%). Reversible hypotension (systolic blood
      pressure < 90, but > 60 mmHg) occurred in 14 patients (2.0%) and was corrected
      with intravenous crystalloid bolus or flumazenil (10 cases, 1.4%) or inotrope
      infusion (4 cases, 0.6%). No patient stay was prolonged due to sedation. Only
      five patients (0.7%) had any recollection of the procedure, while two (0.3%) were
      aware of pain. All hypoxemic episodes occurred during the first hour, whereas 43%
      (6/14) of hypotensive episodes occurred after the first hour. CONCLUSION:
      Conscious sedation with intermittent midazolam and fentanyl is safe and
      efficacious for a broad range of EP procedures.

PMID- 12053294
TI  - Clinical trials of glycoprotein IIb/IIIa inhibitors.
AB  - Glycoprotein (GP) IIb/IIIa inhibitors were developed to block platelet
      aggregation and potentially to abolish thrombus formation. Clinical trials have
      demonstrated that GP IIb/IIIa inhibitors are more potent antithrombotic agents
      than aspirin and heparin alone. GP IIb/IIIa inhibitors reduce short- and long
      term complications of percutaneous revascularization. These agents also are
      effective as adjuncts to various treatment strategies for the management of
      patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQMI).
      Furthermore, recent clinical trials with a small number of patients suggest that
      GP IIb/IIIa inhibitors in combination with low-dose fibrinolytics are safe and
      effective for the treatment of ST segment elevation myocardial infarction. The
      clinical trials of GP IIb/IIIa inhibitors summarized here examined different
      patient populations managed under different strategies. Moreover, these agents
      have different indications for clinical use and varying safety profiles.

PMID- 12053296
TI  - A novel automated injection system for angiography.
AB  - The present method of performing manual coronary angiography requires repetitive
      manipulation of a cumbersome stopcock-manifold system and contrast injection by
      hand syringe. This study reports a novel mechanical contrast injector with
      automated manifold that provides finger touch operator-controlled contrast
      injections. The ACIST Injection System components include a software-controlled
      syringe injector, a disposable automated manifold without stopcocks, a disposable
      hand controller, and a touch screen control panel. The ACIST system was evaluated
      in 50 patients undergoing diagnostic coronary angiography (n = 37) or coronary
      interventions (n = 13). In all cases, the system was easy to use and provided
      excellent quality images even with four catheters, as well as imaging during
      stent positioning with 6Fr guides. This mechanical injector facilitates precision
      operator-controlled angiographic injections, provides superb high quality
      coronary images even with very small lumen catheters, and expedites
      ventriculography during angiographic procedures.

PMID- 12053297
TI  - Directional coronary atherectomy: the Vienna experience.
AB  - BACKGROUND: Several multicenter trials have shown excellent results for
      directional coronary atherectomy (DCA) in a selected patient cohort. To prove the
      applicability of this method in daily clinical routine and a nonselected patient
      cohort, we analyzed 46 consecutive cases performed at our catheterization lab.
      METHODS: DCA was performed as a routine procedure in 45 suitable patients.
      Balloon dilatation or stent implantation postprocedure was accomplished only in
      case of unsatisfactory results. Quantitative coronary angiography was achieved
      pre- and postprocedure as well as at 6-month follow-up. RESULTS: Optimal
      atherectomy < 20% residual stenosis was reached in 24 (52%) of 46 target lesions
      and a residual stenosis < 50% in 46 (100%) lesions. Procedure-related
      complications occurred in three (6%) patients (one major complication, death, <
      24 hours, 2%; two minor complications, pseudoaneurysm, 4%). The 6-month
      angiographic follow-up revealed a binary restenosis rate of 29% (n = 11). Ten out
      of 11 restenotic lesions required revascularization. When patients were
      stratified in two groups according to their preprocedural minimal lumen diameter
      (MLD), this parameter proved to be a very strong predictor of outcome. The
      percentage of restenosis was significantly higher in patients with an MLD > 1.60
      mm compared to patients with a smaller MLD (54% vs 19.3%; P < 0.0001). Reference
      vessel diameter preprocedure did not differ significantly. CONCLUSIONS: Our study
      demonstrated that DCA is a suitable technique for the daily clinical routine, as
      the rates of complications and restenosis were similar to that in a highly
      selective patient cohort. Additionally, our study showed that patient selection
      should include preprocedural analysis of MLD in order to achieve optimal results.
      Therefore, atherectomy yielded comparable results to other conventional
      techniques and may be used instead of or in combination with them.

PMID- 12053298
TI  - Improved outcomes associated with stenting in the healthcare cost and utilization
      project.
AB  - Recent results from Medicare indicated that both hospital mortality and the use
      of same admission coronary artery bypass graft (CABG) surgery were lower in
      patients receiving stents, and that stenting did not alter the finding of
      improved outcomes at high volume centers. The purpose of this report is to
      compare outcomes in a national sample of patients of all ages receiving stents
      with those undergoing conventional balloon angioplasty. A second purpose is to
      evaluate the volume outcome hypothesis. This study included 100,318 angioplasties
      from 191 hospitals in 19 states; 43,966 (44%) involved stent placement. The major
      outcomes of interest were same admission hospital death and same admission CABG
      surgery. In comparison to patients with conventional angioplasty, patients
      receiving stents were younger, less often female and nonwhite, and had less
      diabetes and hypertension. In the group without infarction, hospital mortality
      was lower in the stent group (0.7% vs 0.9%, P = 0.01), as was the use of same
      admission bypass surgery (1.4% vs 2.7%, P < 0.0001). The same pattern was true
      for myocardial infarction; hospital mortality (2.7% vs 4.2%, P < 0.0001) and
      bypass surgery rates (1.6% vs 5.3%, P < 0.0001) were lower in the stent group.
      These results persisted after adjustment for important predictors of outcome. In
      general, outcomes were better in high volume centers, although in the stent
      group, there was no clear relationship between volume and outcome. These results
      support earlier findings that hospital mortality and particularly same admission
      surgery rates are lower with stenting. Although the volume outcome association
      for stenting was less clear in this study than in Medicare, these results do not
      mean that the fundamental volume outcome relationship has been changed by
      stenting.

PMID- 12053299
TI  - Transcatheter coil closure of muscular ventricular septal defects.
AB  - We report two patients with small, muscular ventricular septal defects, both of
      whom had a potential risk of infective endocarditis and underwent transcatheter
      closure using a detachable Cook coil. We suggest that in selected patients this
      technique offers a simple and cost-effective alternative to surgery or double
      disc device procedures.

PMID- 12053300
TI  - Comparison between the safety profile and clinical results of the Cook detachable
      and Gianturco coils for transcatheter closure of patent ductus arteriosus in 272
      patients.
AB  - OBJECTIVES: We evaluated the occlusion rate and safety of Cook detachable coils
      versus Gianturco coils in transcatheter closure of patent ductus arteriosus
      (PDA). BACKGROUND: The Cook detachable coil recently was introduced in an attempt
      to improve the safety of transcatheter closure of PDA. METHODS: Between January
      1994 and September 1998, 272 patients underwent transcatheter PDA closure. Cook
      detachable coils were used in 137 patients, with a mean age of 43.9 months and
      weight of 13.8 kg. In 135 patients, Gianturco coils were used, with a mean age of
      56.8 months and weight of 17.8 kg. The mean narrowest diameter of the PDA in the
      Cook detachable coil group was 2.85 mm versus 2.32 mm for the Gianturco coil
      group. RESULTS: The Cook detachable coil group was younger and weighed less than
      the Gianturco group (P < 0.05 and 0.02, respectively). Their narrowest PDA
      diameter was larger (P < 0.01). Embolization rate was significantly lower in the
      Cook coil group (9[6.5%] of 137 vs 22 (16.3%) of 135; P = < 0.013). The mean
      follow-up for the Cook coil group was significantly shorter (0.55 years) than for
      the Gianturco coil group (1.18 years; P < 0.001). On an intention-to-treat basis,
      complete occlusion by echocardiography was achieved in 99 (72.3%) of 137 patients
      in the Cook detachable coil group, which was significantly less than the
      Gianturco coil group (114 [84.4%] of 135; P = 0.008). CONCLUSION: Cook detachable
      coils for transcatheter closures of the PDA are safer than Gianturco coils.
      Hence, children with large ductal can be treated earlier in life. Short-term
      complete occlusion rate was lower in the Cook detachable coil group. This rate
      can be explained by a shorter follow-up time, larger ductal diameter, and the
      different materials used for the detachable coils.

PMID- 12053301
TI  - Use of fenoldopam for prevention of radiocontrast nephropathy in the cardiac
      catheterization laboratory: a case series.
AB  - Many of the longstanding challenges in interventional cardiology, such as
      restenosis and thrombosis, have been met. However, radiocontrast-induced
      nephropathy (RCN) continues to be problematic, particularly as the population of
      patients who are diagnosed and treated for vascular occlusions in the cardiac
      catheterization laboratory have become increasingly older and more complex.
      Introduction of nonionic contrast media has not eliminated this problem. We
      present the cases of four high risk patients whom we treated with a newly
      available renal vasodilator, fenoldopam, as a strategy to prevent RCN and its
      associated morbidity and mortality.

PMID- 12053302
TI  - Covered stents in the treatment of aortic coarctation.
AB  - Coarctation of the aorta can be managed in different ways depending upon the age
      of presentation, anatomical details of the coarctation, the aortic arch anatomy,
      and whether the coarctation is native or a recurrence following surgery. In
      infants, surgery is the preferred treatment of choice, whereas in older children
      and adults, percutaneous procedures, such as balloon angioplasty or stent
      implantation, are becoming increasingly popular methods for treating coarctation.
      Various types of stents have been used and this paper specifically addresses the
      use of covered or graft Jomed stents in a small group of patients with
      coarctation.

PMID- 12053303
TI  - Echocardiographically guided closure of a patent foramen ovale during pregnancy
      after recurrent strokes.
AB  - BACKGROUND: Stroke during pregnancy and puerperium is a severe complication that
      causes high morbidity and mortality. A patent foramen ovale (PFO) allowing
      paradoxical embolism is one identified risk factor. CASE: A 25-year-old pregnant
      woman with PFO suffered from recurrent cerebral embolism. To prevent recurrent
      cerebral embolism during pregnancy, delivery, and puerperium, interventional
      closure of the PFO was performed without fluoroscopy under echocardiographic
      guidance. The postinterventional course was uneventful. CONCLUSION: Percutaneous
      transvenous closure of a PFO during pregnancy is feasible without the use of
      fluoroscopy.

PMID- 12053304
TI  - Transcatheter closure of secundum atrial septal defect with a new self-expanding
      nitinol double disk device (Amplatzer device): experience in Nanjing.
AB  - PURPOSE: Various devices have been developed for the transcatheter closure of
      secundum atrial septal defect (ASD II) to avoid the morbidity, discomfort, and
      thoracotomy scar associated with surgical closure. The purpose of this study was
      to evaluate the safety and efficacy of the Amplatzer septal occluder for
      transcatheter closure of ASD II. PATIENTS AND METHODS: Only patients who were
      clinically diagnosed with ASD II were selected. The anatomy of ASD had to meet
      certain echocardiographic criteria. Under the guidance of echocardiography and
      fluoroscopy, the implantation of the device was accomplished as recommended by
      the manufacturer. RESULTS: Thirty patients (median age 18.4 years) with an ASD II
      underwent transcatheter closure. Procedure time ranged from 30-200 minutes and
      fluoroscopy time from 10-50 minutes. The diameter of the ASD measured by
      echocardiography ranged from 13-25 mm, while both the stretched diameters of the
      ASDs and the sizes of the devices ranged from 18-34 mm. The successful placement
      rate was 100%. The residual shunt rate was 100% immediately after device
      implantation and 10% after 24 hours. After 3 months, 3.3% of the patients had a
      (trivial) residual shunt. The device did not affect the surrounding structures of
      ASD. No embolization of the device occurred. CONCLUSION: The Amplatzer device
      designed for the closure of ASD II can be implanted easily and also is
      retrievable. Due to a low ratio of residual shunt and few complications, this
      device is a good choice for transcatheter closure of ASD II. Long-term follow-up
      will be required for widespread clinical use.

PMID- 12053305
TI  - Neurological aspects of patent foramen ovale: in search of the optimal treatment.
AB  - Although paradoxical embolism through a patent foramen ovale (PFO) has become an
      established cause of cerebral ischemia in younger patients without other obvious
      causes of stroke, the therapeutic options have not been investigated
      satisfactorily. There are still uncertainties about the natural history of PFO
      patients after suffering a stroke, and diagnostic criteria proving a causal and
      not incidental relation to the embolic event are not established. The stroke
      recurrence has been evaluated in several studies in a heterogeneous population
      and seems as low as 1.9% per year. Secondary prophylactic treatment has become a
      matter of discussion since efforts were made to close the PFO either surgically
      or by percutaneous transcatheter methods. Foramen closure seems to be effective
      in eliminating the mechanism of paradoxical embolism but its benefit-risk ratio
      has yet to be established. Following the goals of evidence-based medicine, none
      of the therapeutic options can be recommended. Fortunately, the issue has gone to
      trial and there are two studies underway to compare foramen closure to medical
      therapy.

PMID- 12053306
TI  - Percutaneous closure of patent foramen ovale in symptomatic patients.
AB  - BACKGROUND: Patent foramen ovale (PFO) and atrial septal aneurysm (ASA) have been
      associated with stroke in young adults. Patients with PFO suffering from
      paradoxical embolism are at increased risk for recurrent events. Percutaneous PFO
      closure is a new treatment modality aimed at secondary prevention. METHODS AND
      RESULTS: Since April 1994, 132 consecutive patients, aged 51 +/- 12 years with
      PFO and with at least one paradoxical embolic event, underwent percutaneous PFO
      closure using six different device types. The embolic index event was an ischemic
      stroke in 62% of patients, a transient ischemic attack (TIA) in 33% of patients,
      and a peripheral embolism in 5% of patients. Thirty-six (27%) patients had PFO
      associated with ASA, whereas 96 (73%) patients had PFO only. The implantation
      procedure was successful in 130 (98%) patients. During and up to 6 years of
      follow-up (mean 1.8 +/- 1.6 years, 231 patient years), a total of eight recurrent
      embolic events were observed, with six TIAs, two peripheral emboli, and no
      ischemic stroke. The actuarial freedom from recurrence of the combined end point
      of TIA, ischemic stroke, and peripheral embolism was 95.3% (95% confidence
      interval [CI], 91.0%-96.4%) at 1 year and 90.5% (95% CI, 83.6%-97.2%) at 6 years.
      CONCLUSIONS: Percutaneous PFO closure can be performed with a high success rate.
      The procedure appears a promising therapeutic modality for secondary prevention
      of recurrent embolism in patients with PFO. Randomized trials must define its
      therapeutic value.

PMID- 12053307
TI  - From disk devices to transcatheter patches: the evolution of wireless heart
      defect occlusion.
AB  - Since 1988, we have been using double-disk devices with several device
      generations and improving results. Our current disk device, "The ButtonSeal
      Centering on Demand Device," is a multipurpose device made of stainless steel and
      polyurethane. It has shown high occlusion rates and no significant complications
      in atrial septal defects (ASDs) up to 30 mm in diameter. It can be used according
      to the ASD anatomy both in large, single defects (centering) and in multiple
      fenestrations (noncentering). The ButtonSeal shares the same limitations as other
      disk devices, namely, the possibility of wire-related problems and the need for
      significant septal rim. The development of wireless balloon-delivered devices and
      patches addresses these problems and limitations. Both detachable balloon devices
      and patches were used experimentally in animals and in feasibility studies in
      humans. The results showed good occlusion rates and lack of wire-related
      complications. Both methods required a minimal rim and occluded more defects than
      the disk devices. The transcatheter patch method was safer and had only one
      disadvantage, which was the need for 48-hour balloon support.

PMID- 12053308
TI  - An unusual encounter of a "cobra" in the heart: rare appearance of an Amplatzer
      Septal Occluder.
AB  - This article presents the unusual appearance of a "cobra" due to "acute bending"
      of the proximal part and partial opening of the distal part of the left atrial
      disk of an Amplatzer Septal Occluder during the process of transcatheter closure
      of a secundum atrial septal defect in a 6-year-old boy. The possible reasons and
      method to overcome this technical problem, which resulted in successful occlusion
      of the atrial septal defect, are discussed.

PMID- 12053309
TI  - Transcatheter closure of muscular ventricular septal defects in two patients
      after myocardial infarction.
AB  - Acquired muscular ventricular septal defects (MVSD) after myocardial infarction
      (MI) can lead to right heart failure and cardiogenic shock with high mortality.
      Early surgical therapy is often difficult to perform but can reduce the
      mortality. The closure of congenital septal defects is performed with high
      safety. Therefore, the interventional closure of an acquired post-MI VSD might be
      feasible and of potential benefit. To date, experiences with closure of post-MI
      MVSDs are minimal. We report on two patients with post-MI VSD.

PMID- 12053310
TI  - Catheter closure of the persistent foramen ovale: mid-term results in 162
      patients.
AB  - Four different types of occluder systems were used to close a persistent foramen
      ovale (PFO) in 162 patients with paradoxical embolic events. Ninety-eight
      patients had ischemic stroke, 60 transient ischemic attacks (TIA) or prolonged
      reversible ischemic neurological deficit (PRIND), and 4 had peripheral arterial
      embolism. The age of the patients was 40.2 +/- 11.9 years and the ischemic event
      had happened 7 +/- 10 months before device closure. CardioSeal and Amplatzer
      occluders were the most commonly used devices (73 and 77 cases, respectively).
      Implantations were successful in all patients. Serious catheter-related
      complications included two device embolizations and two venous bleedings. Six
      patients had documented supraventricular arrhythmias within the first month after
      implantation, which disappeared spontaneously within some weeks without therapy
      in three patients; the other three patients with atrial fibrillation needed
      conversion to sinus rhythm. Residual leaks were found in 5 out of 116 patients
      who had been followed by transesophageal echocardiography (TEE) and one leak was
      closed by a second device. During a follow-up period of 19.4 +/- 16.2 months per
      patient, TIA and PRIND occurred in 3 of 116 patients. Interventional closure of
      PFO is a simple, effective and quick method that is superior to surgery and
      avoids the problems of life-long anticoagulation.

PMID- 12053311
TI  - The duct-occlud device: design, clinical results, and future directions.
AB  - The successful employment of embolization coils for transcatheter occlusion of
      the patent ductus arteriosus (PDA) has resulted in acceptance of transcatheter
      occlusion as the treatment of choice for small to medium-sized PDAs. The Duct
      Occlud device was developed to further improve the technique by utilizing a
      controlled release mechanism and coil shape specifically designed for the
      geometry of the ductus arteriosus. Clinical studies have demonstrated excellent
      efficacy with low embolization rates and low incidences of complications. Newer
      modifications have been designed for occlusion of larger PDAs and subaortic
      ventricular septal defects, and preliminary clinical results have been promising.

PMID- 12053312
TI  - The Sideris buttoned devices for transcatheter closure of patent ductus
      arteriosus.
AB  - This article reviews the experience in the last decade with Sideris buttoned
      devices for occlusion of patent ductus arteriosus (PDA). The devices used were
      the regular buttoned device, the infant buttoned device, the device with the
      folding plug, and the wireless device. The buttoned devices were implanted
      transvenously and introduced through 7Fr-8Fr long sheaths for PDAs up to 12 mm;
      wireless devices required 9Fr-11Fr sheaths for PDAs up to 22 mm. All different
      shapes of ductus were occluded. The records of 356 patients in the international
      and Food and Drug Administration (FDA) supervised United States (US) clinical
      trials were reviewed. Despite excellent long-term full occlusion rates and the
      absence of significant complications with the regular buttoned device,
      modifications were necessary to improve the full occlusion rates in 24 hours. The
      24-hour rates improved from 60% with the regular device to 85% with the folding
      plug device. Most residual shunts disappeared on long-term follow-up without
      significant complications. Wireless devices were developed for very large PDAs
      and have excellent occlusion rates. The buttoned device with the incorporated
      folding plug and the wireless devices are currently under clinical trial. The
      safety record of the new devices needs to be established with larger clinical
      trials.

PMID- 12053313
TI  - Patent ductus arteriosus equipment and technique. Amplatzer duct occluder:
      intermediate-term follow-up and technical considerations.
AB  - Between May 1997 and June 2000, 69 patients, ages 0.1 to 34 years, underwent
      attempted anterograde transcatheter closure of a patent ductus arteriosus (PDA)
      using the Amplatzer Duct Occluder (ADO). The ADO is a cone-shaped, self
      centering, and repositionable occluder made of nitinol wire mesh. A 5Fr to 7Fr
      sheath was used for the delivery of the device. The mean PDA diameter (at the
      pulmonary end) was 4.6 +/- 1.9 mm (range 1 mm-8.5 mm). Sixty-seven of the 69
      patients had successful device placement. The mean ADO smallest diameter was 6.9
      +/- 1.8 mm (range 4 mm-12 mm). Complete angiographic closure occurred in 62
      (92.5%) of 67 patients (95% confidence interval, 88.22%-98.77%). In five
      patients, there was a trivial residual shunt immediately after the procedure. At
      24 hours, color Doppler flow imaging revealed complete closure in all 67 (100%)
      patients. The unsuccessful attempts occurred in two patients with a small, 1-mm
      diameter native PDA and residual PDA after surgical occlusion. Fluoroscopy time
      was 7.6 +/- 1.8 minutes (4 min-18 min). No complications were observed. At a
      median follow-up of 1.5 years (range 0.25 to 3.2 years), all patients had
      complete closure without complications. We conclude that transcatheter closure
      using the ADO is a highly effective and safe treatment for most patients with
      PDA.

PMID- 12053314
TI  - Patent ductus arteriosus: catheter closure in the adult patient.

PMID- 12053315
TI  - Patent foramen ovale closure in patients with transient ischemia attack/stroke.
AB  - Paradoxical embolism through a patent foramen ovale (PFO) has been recognized as
      a potential cause of transient ischemia attack (TIA) and stroke especially in
      younger patients. The therapeutic options are medical treatment (antiaggregation
      or anticoagulation) with an annual recurrence rate of 3% to 4% for stroke or TIA,
      surgical PFO closure, or catheter closure. Randomized studies are ongoing;
      however, the results will not be available soon. Since August 1994, we have
      attempted catheter closure of a PFO in 281 patients (age 17 to 79 years, mean
      46.8 +/- 13.2) with paradoxical embolism. Of these, 184 patients had at least one
      embolic stroke, 112 patients at least one TIA, and 15 patients at least one
      peripheral embolism. The diameter of the PFO, measured with a balloon catheter,
      ranged from 3 mm to 24 mm with a mean of 10 +/- 3.5 mm. Implantation of the
      occluder was technically successful in all patients (two attempts in four
      patients). Seven different devices were used: 26 Sideris buttoned, 11 ASDOS, 19
      Angel Wings, 98 PFO-Star, 37 Cardioseal-Starflex, 57 Amplatzer and, 33 Helex
      devices. One patient suffered from septicemia and subsequently died. In 2
      patients, device embolization occurred during or after the procedure (1 Sideris,
      1 PFO-Star; catheter retrieval successful). Thirty-seven patients had other minor
      complications without long-term sequelae: atrial fibrillation within the first
      weeks after implantation in five patients, asymptomatic thrombus on the device at
      routine transesophageal echocardiogram (TEE) in 7 patients (1 Angel Wings, 1
      ASDOS, 1 CardioSeal, 4 PFO-Star), and device frame fracture in 25 patients (2
      Sideris, 4 ASDOS, 1 Angel Wings, 1 CardioSeal, 17 PFO-Star). No complications
      occurred with the newer devices (Amplatzer and Helex). A residual shunt after 6
      months was found in 5.5% of the patients who had completed their 6-month TEE
      follow-up. In two patients, a second occluder was implanted because of a residual
      shunt. During a follow-up period of 1 month to 71 months (mean 12 +/- 16 months,
      268 patient years), a recurrence of an embolic event (seven TIA, two stroke)
      occurred in eight patients. None of these occurred with the newer devices
      (Amplatzer, Helex). Freedom from recurrence of the combined end point of TIA,
      ischemic stroke, and peripheral embolism was 95.7% (95% CI: 89.0%-98.4%) at 1
      year and 94.1% (95% CI: 80.1-98.4%) at 3 years. Catheter PFO closure is a
      technically simple procedure. With the newer devices and increasing experience,
      the success rate has improved and the complication rate has decreased. The
      advantage of the procedure is that closing the defect means a causal treatment.
      However, catheter closure of PFO despite a very low morbidity has inherent
      potential risks like any other interventional procedure. Furthermore, selection
      of patients who definitely have PFO as the cause of their cerebral event has not
      been defined. For these reasons, further studies are warranted.

PMID- 12053316
TI  - Closure of atrial septal defects in adult patients: justification of the "tipping
      point".
AB  - The "tipping point," favoring closure of hemodynamically significant atrial
      septal defects (ASDs) in the adult, has occurred and is supported by strong
      clinical data, especially in patients who present with symptoms.
      Echocardiographic evidence of right ventricular volume overload as a correlate of
      significant left-to-right intracardiac shunting remains a prerequisite to
      determine need for closure, even in patients with child-bearing potential. No
      patient appears too old to achieve benefit from closure of such defects. Modern
      therapeutics for pulmonary vascular disease may allow extension of these
      techniques to an increasingly threatened population, with care best coordinated
      and offered in appropriate centers of expertise.

PMID- 12053317
TI  - Initial and follow-up results of the Tenax coronary stent.
AB  - The Tenax coronary stent is laser sculpted from high precision 316 L stainless
      steel using advanced production procedures. An a-SiC: H (hydrogen-rich amorphous
      silicon carbide) coating reduces its thrombogenicity and improves its
      biocompatibility. From April to July 1998, 266 stents were implanted in 241
      patients (aged 62.7 +/- 10.5 years) in five centers. The clinical indication for
      intervention was unstable angina (33.2%) and recent myocardial infarction (29.5%)
      in many cases. Most lesions (53.8%) had complex characteristics (Class B2 or C).
      The target vessel was the LAD in 42.5% and the right coronary artery in 36.8% of
      all cases. Four primary stent deployment failures occurred and implantation was
      successful in 259 (97.4%) of 266 stents. No death and no Q-wave myocardial
      infarction or emergency CABG occurred during hospital stay. Clinical success,
      defined as successful deployment without procedural or clinical event, was
      achieved in 230 (95.4%) of 241 patients. One-year clinical follow-up shows a low
      need for target lesion revascularization (17/237 [7.1%] patients) and a 15.8%
      rate of major adverse cardiac events (36/237 patients). The clinical and
      angiographic outcomes of our study suggest that the hybrid, amorphous
      hydrogenated silicon carbide coated design is promising and merits further
      evaluation in larger clinical trials.

PMID- 12053318
TI  - Coronary revascularization: an opportunity for lipid screening and treatment.

PMID- 12053319
TI  - Percutaneous transluminal angioplasty of the anomalous circumflex artery.
AB  - The technical experience reported in the literature concerning angioplasty in
      patients with anomalous origin of the left circumflex artery is limited. Balloon
      angioplasty seems to be a favorable approach for revascularization in these
      vessels, and major determinants of successful angioplasty are angiographic
      knowledge of their course and structure, appropriate selection of guiding
      catheter, and the possibility of advancing the balloon into the anomalous vessel.
      Five consecutive patients with severe atherosclerotic lesions on the anomalous
      left circumflex artery who underwent coronary angioplasty of the anomalous vessel
      are reported. Angiographic and clinical success were achieved in three patients
      with balloon alone and in one with stent implantation.

PMID- 12053320
TI  - Guides and wires.

PMID- 12053321
TI  - Difficult percutaneous mitral commissurotomy: failure of the Inoue balloon
      technique and successful double-balloon technique.
AB  - From December 1994 to May 1999, 487 patients underwent percutaneous transvenous
      mitral commissurotomy according to the Inoue balloon technique for tight mitral
      stenosis. In three cases, the Inoue balloon technique was not possible because
      the catheter balloon could not enter the mitral orifice and the double-balloon
      technique was performed instead. In two cases, a flow-guided balloon catheter met
      the mitral orifice and the double-balloon technique was effective. In the third
      case, passing the valve with a flow balloon catheter was impossible, a 0.032"
      Terumo straight wire crossed the valve, which was dilated with a single balloon
      the first time and a double balloon the second time. The mitral valve area
      increased in the three cases from 0.8 to 1.8 cm2, from 0.7 to 1.6 cm2, and from
      0.5 to 1.5 cm2, respectively. There were no complications.

PMID- 12053323
TI  - Rheolytic thrombectomy for in-stent thrombosis: creating a diagnostic window.
AB  - Acute-stent thrombosis is a relatively uncommon complication of coronary artery
      stenting, however, it is a potentially catastrophic event. In this case report of
      stent thrombosis, rheolytic thrombectomy is used to reestablished flow within the
      artery and, thereby, facilitate intravascular ultrasound. This documented that
      inadequate stent expansion, residual disease, and tissue prolapse through the
      stent at an angulated segment of the artery are factors that may underlie
      thrombosis. This case illustrates that rheolytic thrombectomy is feasible in
      subacute thrombosis, and that this approach facilitates diagnostic evaluation and
      treatment of underlying factors involved in stent thrombosis.

PMID- 12053322
TI  - Y stenting of a bifurcation stenosis using a new radiopaque stent.
AB  - A case of Y stenting using radiopaque stents for a bifurcation stenosis is
      described. Angiography and intravascular ultrasound demonstrate that in spite of
      optimal stent placement there is an area of the lesion that is not fully covered
      by the stents. This may predispose to subacute thrombosis and restenosis. This
      case illustrates a potential deficiency of this type of bifurcation stenting.

PMID- 12053324
TI  - Early experience with the Amplatzer ductal occluder for closure of the
      persistently patent ductus arteriosus.
AB  - Using an Amplatzer duct occluder, 106 patients (weight 21 +/- 18 kg) underwent an
      attempt at catheter closure of a persistently patent ductus arteriosus (PDA).
      Their age ranged from 22 days to 48 years. The PDA measured between 1.2 to 8.1 mm
      at its narrowest diameter. The device was successfully implanted in 105 patients.
      The immediate closure rate was 70% and gradually increased to 100% at 1-month
      follow-up. There was no clinical evidence of hemolysis and no incidence of device
      embolization or bacterial arteritis. Doppler evaluation showed no evidence of
      aortic arch or pulmonary artery obstruction. The device, which is currently
      undergoing multicenter clinical trial in the United States, is proving to be a
      safe and effective device for closure of the persistently PDA.

PMID- 12053325
TI  - Transcatheter closure of atrial septal defects in children & adults using the
      Amplatzer Septal Occluder.
AB  - We are reporting the worldwide experience in closing atrial septal defects (ASDs)
      in children and adults using the Amplatzer Septal Occluder (ASO) as of July 2000.
      The outcome measures were safety and efficacy with special emphasis on: (1)
      immediate success of the ASD closure as measured by transesophageal
      echocardiography (TEE), (2) short- and medium-term follow-up at 24 hours and 1
      and 3 months and long-term follow-up at 1, 2, and 3 years as assessed by
      transthoracic echocardiography (TTE); and (3) the incidence of complications. In
      all, 3580 procedures were performed in 3535 patients. In 75 patients, the device
      was not implanted for variety of reasons; 3460 patients received a single ASO
      device and 45 received two devices for multiple ASDs. The median age of the
      patients was 12.1 year, (range, 10 days-88 years, the median weight was 41.0 kg
      (range, 2.4-137 kg) and the median Qp/Qs ratio was 2 (range, 0.3-10). The median
      size of ASD by TEE was 14 mm (range, 1-38 mm) and the median stretched diameter
      was 18 mm (range, 4-44 mm). The median size of device implanted was 18 mm (range,
      4-40 mm). The median fluoroscopy time was 17.1 minutes (range, 0.0-194.0
      minutes). The immediate success rate including those patients with complete
      closure, trivial residual shunt, or with small residual shunt was 97.4%. This
      increased to 99.2% and 100% at 3 months and 3 years, respectively. Minor
      complications were encountered in 2.8% of procedures, while serious complications
      occurred in less than 0.3% of the cases. There were no device related deaths. We
      conclude that the ASO is a safe and effective device for catheter closure of
      small to large ASDs up to a stretched diameter of 40 mm in children and adults
      with very high short-, medium, and long-term success rates.

PMID- 12053326
TI  - The use of Amplatzer devices to occlude vascular fistulae.
AB  - The Amplatzer occluders are Nitinol-based devices that are preshaped for specific
      indications, primarily to close atrial septal defects, patent foramen
      ovale/fenestrations, or to occlude patent arterial ducts or one designed
      specifically for closure of ventricular septal defects. The flexible quality of
      the Nitinol together with the different designs of Amplatzer occluders make it
      possible for these plug devices to be used for conditions other than what they
      are designed for. This is particularly the case for fistulae where no specific
      devices are available and hence improvisation may be required. The established
      use of the Amplatzer occluder devices primarily for atrial septal defects and for
      patent arterial ducts provide the confidence to use them for alternative
      conditions where few or no alternatives are available or if surgery is the only
      option. This article describes the use of Amplatzer occluder devices for two
      unusual conditions, namely to occlude a pulmonary arteriovenous malformation and
      to close an aorto-left ventricular tunnel.

PMID- 12053327
TI  - Catheter closure of atrial septal defects and patent foramen ovale in patients
      with an atrial septal aneurysm using different devices.
AB  - BACKGROUND: Atrial septal aneurysm is frequently associated with patent foramen
      ovale (PFO) and atrial septal defects (ASD). Moreover, a relationship between
      atrial septal aneurysm and embolic cerebrovascular events has been suggested. The
      aims of this study were to analyze morphological and functional characteristics
      of atrial septal aneurysm in PFO and ASD patients and to assess the feasibility
      and efficacy of different devices for transcatheter closure and the influence of
      atrial septal aneurysm. METHODS: Between March 1997 and May 2000 transcatheter
      ASD or PFO closure was attempted in 63 patients (mean age 47 +/- 13 years) with
      an atrial septal aneurysm using one of the following devices: Angelwings (n = 3),
      Cardioseal (n = 5), Cardioseal-Starflex (n = 7), Amplatzer (n = 11), Amplatzer
      PFO (n = 5), PFO-Star (n = 25), or Helex (n = 7). RESULTS: Implantation was
      primarily successful (after the first or second attempt) in all patients. One PFO
      Star device embolized 12 hours after the procedure. During follow-up (0.6-37
      months, mean 10.4 +/- 9.2) a residual shunt could be detected by transesophageal
      echocardiography after 2 weeks in four patients and after 6 months in one
      patient. Three PFO patients had cerebrovascular events after implantation. Two
      patients had a transient ischemic attack (TIA) and one patient a stroke. A
      thrombus formation on the device detected in three patients disappeared after
      antithrombotic therapy. CONCLUSION: We conclude that ASDs and PFOs with an
      associated atrial septal aneurysm can be closed with different available devices.
      There seem to be no additional risks compared with patients without atrial septal
      aneurysm.

PMID- 12053328
TI  - Hypoxemia related to right-to-left shunting through a patent foramen ovale:
      successful percutaneous treatment with the CardioSeal device.
AB  - Hypoxemia related to right-to-left shunting through a patent foramen ovale (PFO)
      is not rare. It can be observed in correlation with a specific situation such as
      pneumonectomy and can occur even with normal pulmonary pressure. This article
      reports the experience of 12 patients in which a transcatheter closure with the
      CardioSeal device was done successfully. Clinical improvement is often obtained,
      despite incomplete occlusion of the defects. The author demonstrated that
      transcatheter closure of PFO can be performed safety and should be considered as
      an efficient alternative to surgery in cyanotic patients with PFO.

PMID- 12053329
TI  - Percutaneous closure of large atrial septal defects with the Amplatzer Septal
      Occluder: technical overkill or recommendable alternative treatment?
AB  - To judge whether an Amplatzer Septal Occluder (ASO) can be used as a safe therapy
      instead of surgery for closure of large atrial septal defects > 25 mm in
      diameter, we report our experiences in 45 patients out of a cohort of 467
      patients after successful ASO implantation within a period of 3 years. Median
      defect diameter was 28 mm (range 25-36), median age was 41.2 years (range 10.1
      77.7 years). Body weight ranged from 33.5 to 112.0 kg (median 68 kg). Due to an
      inevitable reduction of the stent size with increasing distances of the discs
      fixed at the thicker part of the atrial septum in larger defects, we implanted
      devices 2-4 mm larger than the measured stretched diameter. Fluoroscopy times
      ranged from 2.0 to 24.4 minutes, with a median of 10.3 minutes. Follow-up studies
      were obtained after 48 hours and 1, 6, and 12 months, and then yearly. The median
      period of follow-up was 0.82 years (range 0.1-2.6). The complete occlusion rate
      was 91.1%. A trivial hemodynamically insignificant residual shunt remained in
      8.9% of the patients. Three patients showed transient atrial tachyarrhythmias
      within the first 3 months after implantation and three remained in chronic atrial
      fibrillation. The excellent results in the short and medium term make Amplatzer
      device implantation a recommendable safe and effective alternative to surgery,
      even in selected cases with defects > 25 mm. Final judgement, however, is only
      possible after long-term follow-up.

PMID- 12053330
TI  - StarFlex ASD closure: deployment, techniques, equipment.

PMID- 12053331
TI  - Role of manual compression time and bed rest duration on the occurrence of
      femoral bleeding complications after sheath retrieval following 4Fr left-sided
      cardiac catheterization.
AB  - To shorten hospital stay or to allow ambulatory procedures, 4Fr catheters for
      left-sided cardiac catheterization can be used. These latter parameters may also
      be influenced by compression time and bed rest duration. The role of these
      parameters was assessed by prospectively including 130 consecutive patients who
      underwent 4Fr femoral diagnostic procedures. The patients were randomized into
      two groups: group 1 consisted of 70 patients undergoing 5-minute compression and
      group 2 consisted of 60 patients with 15-minute compression. In each group, a
      second randomization was applied to determine the bed rest duration (2-4 hours).
      More group 1 patients experienced immediate bleeding following manual compression
      than group 2 patients (12 [17%] vs 3 [5%], P < 0.03, respectively). Compared to
      group 2, a slight but nonsignificant increase in the total number of hematomas
      was observed in group 1 (31 vs 22%, NS). No difference existed in terms of local
      large hematomas at 24 hours (7% in each group) or in terms of benign > or = 10 cm
      diffuse subcutaneous ecchymosis at 7-day follow-up (13 [19%] group 1 patients vs
      8 [13%] group 2 patients, NS). However, persistence of diffuse subcutaneous
      ecchymosis at 7-day follow-up appeared to be related to the history of immediate
      bleeding following manual compression in both groups (group 1: 5/13 vs 7/57
      patients [P < 0.04] and group 2: 3/8 vs 0/52 patients [P < 0.002]). In
      conclusion, 4Fr femoral left-sided cardiac catheterization is safe and could be
      performed as an ambulatory procedure. However, it requires 15-minute duration of
      manual compression associated with 2-hour bed rest to decrease local bleeding
      complications.

PMID- 12053332
TI  - Microvena atrial septal defect occlusion device--update 2000.
AB  - This article (1) summarizes the Duke University results with the Das-Angel Wings
      atrial septal defect occlusion device, (2) outlines the rationale for design
      changes in the device, and (3) describes the new Microvena atrial septal defect
      occlusion device characteristics, and plans for the future. At Duke University,
      investigators using the first-generation device attempted closures in 35 patients
      with atrial level communications. Ages ranged from 5 to 83 years with a median of
      28 years, and weights ranged from 16 to 100 kg. Thirty-two of the 35 defects had
      successful device placement. On follow-up, the defects of 27 of 32 patients with
      an implanted device were completely closed, and 5 patients had < 2-mm residual
      leaks. Three patients had malposition of the device, two of whom were treated
      surgically and one of whom was treated with percutaneous device retrieval.
      Complications included one small mitral valve perforation with no clinical
      sequelae. There have been no strokes, delayed embolizations, nor procedure or
      device related deaths. There have been no new or late problems in the cohort in a
      follow-up extending to 63 months. Opportunities for improvement of the device
      were noted during the clinical study. The manufacturer, Microvena Corporation,
      voluntarily withdrew the occluder for a redesign initiative. The objectives of
      redesign were ready deployment, reduction of device manipulation, rounding of the
      device, and retrievability. The Guardian Angel device has been the product of the
      redesign effort. It is a percutaneously inserted atrial septal defect occlusion
      device that uses the same materials as the initial device, but which has
      advantages of retrievability, repositionability, and no need for device
      manipulation. Initial studies have been performed in experimental animals, and
      clinical trials are planned for the near future.

PMID- 12053333
TI  - Centering-on-demand buttoned device: its role in transcatheter occlusion of
      atrial septal defects.
AB  - Since the initial design and description of the buttoned device, it has undergone
      a number of design changes. Introduction of radiopacity in the knot (button) made
      it easier to visualize and document that buttoning has indeed occurred.
      Introduction of two buttons has markedly decreased the unbuttoning rate with
      potential for eliminating it. A centering mechanism was then incorporated into
      the device, which allowed closure of larger defects and use of smaller-sized
      devices. For some unknown reason, unbuttoning rate no longer occurs since the
      introduction of this device. The centering-on-demand (COD) device also appears to
      have increased the effective occlusion rates. At the present time, however, no
      long-term follow-up data are available to assess the long-term efficacy of the
      new device. Experience in a larger number of patients and evaluation of follow-up
      data are necessary to confirm the safety and efficacy observed in the small
      cohort reported in this review.

PMID- 12053335
TI  - Transcatheter PDA closure: equipment and technique.

PMID- 12053334
TI  - Simultaneous double or triple coil technique for closure of moderate sized (> or
      = 3.0 mm) patent ductus arteriosus.
AB  - One important complication of coil occlusion of patent ductus arteriosus using
      the conventional Gianturco coil is migration of coils into peripheral vessels.
      Especially in patients having relatively larger size ductus, the risk for such
      complication could be increased. In this regard, a detachable coil may have some
      technical benefits in performing coil occlusion and reducing the incidence of
      complications such as migration of coil. Based on our clinical experiences, we
      describe the clinical efficacy of a simultaneous double or triple coil occlusion
      technique using the Cook detachable coil system to close the ductus arteriosus,
      especially in patients whose ductus diameter more than 3.0 mm.

PMID- 12053336
TI  - [Evidence to the treatment of asthma].

PMID- 12053337
TI  - [Environmental and genetic causes of cancer].

PMID- 12053338
TI  - [Is the insurance physician wiser than the treating physician?].

PMID- 12053339
TI  - [The treating physician and the insurance physician against each other?].

PMID- 12053340
TI  - [An hyperactive child].

PMID- 12053341
TI  - [The effects of steroids on connective tissue].

PMID- 12053342
TI  - [The offspring of Influenza A (H3N2) in Finland--30 years of catching and
      following].

PMID- 12053343
TI  - [Differences in cervical cancer mass screening results in Greater-Helsinki area].

PMID- 12053344
TI  - [The impact of environment and inherited factors in carcinogenesis: analyses from
      three Nordic twin studies].

PMID- 12053345
TI  - [Cold and damp legs].

PMID- 12053346
TI  - [Allergic rhinitis, asthma and eczema caused by gum arabic in a candy factory
      worker].

PMID- 12053347
TI  - [Epiglottitis in an adult--a forgotten disease?].

PMID- 12053349
TI  - [Fever, seizures and unconsciousness in a young woman leading to death].

PMID- 12053348
TI  - [Treatment of hyperhidrosis].

PMID- 12053350
TI  - [Panic disorder].

PMID- 12053351
TI  - [Increased urinary frequency in a small boy].

PMID- 12053352
TI  - [On chronic venous insufficiency and varicose ulcer].

PMID- 12053353
TI  - [On causes of recurrent pharyngitis].

PMID- 12053355
TI  - [Spurring into the wind].

PMID- 12053356
TI  - [Diagnostics and therapy of asthma].

PMID- 12053357
TI  - [New hope concerning the prognosis of atherosclerosis].

PMID- 12053358
TI  - [What is the best treatment for atopic dermatitis?].

PMID- 12053359
TI  - [Radiotherapy of benign disorders--a new old treatment method].

PMID- 12053360
TI  - [Henoch-Schonlein purpura in children].

PMID- 12053361
TI  - [Atrioventricular block in a young man].

PMID- 12053362
TI  - [Restless legs].

PMID- 12053363
TI  - [Treatment of nephrotic syndrome in adults].

PMID- 12053364
TI  - [A pricking pastry].

PMID- 12053365
TI  - [A stubborn dermatitis on the forehead].

PMID- 12053366
TI  - [Mouth-to-mouth resuscitation is still needed].

PMID- 12053367
TI  - [Cord blood as a part of the whole in stem cell transplantations].

PMID- 12053368
TI  - [Hypersensitivity to electricity is a polymorphic disorder].

PMID- 12053369
TI  - [Family-orientated medicine--a new viewpoint for physician's work].

PMID- 12053370
TI  - [The effectiveness of family-orientated treatment in the light of research].

PMID- 12053371
TI  - [Does family-orientated medicine offer anything new?].

PMID- 12053373
TI  - [From a doctor to a family doctor].

PMID- 12053372
TI  - [Family doctor's working models and collaboration].

PMID- 12053374
TI  - [Psychosocial problems and the office visit].

PMID- 12053375
TI  - [Somatizing patient--a challenge for general practitioner].

PMID- 12053376
TI  - [Family physician as a support to an adolescent].

PMID- 12053377
TI  - [Child with symptoms as a patient of the family physician].

PMID- 12053379
TI  - Diffuse in-stent restenosis.
AB  - Stent restenosis, especially the diffuse pattern, has developed into a
      significant clinical and economical problem. It has been estimated that up to
      250,000 patients developed in-stent restenosis in 2,000 alone, two thirds of them
      can be expected to have diffuse in-stent restenosis, which is difficult to treat
      because of high recurrence rates. None of the conventionally available
      interventional treatment modalities provides optimal long-term results.
      Intravascular radiation therapy is currently the only effective percutaneous
      therapy for combating in-stent restenosis. Late thrombotic complications have
      largely been eliminated by extended antiplatelet regimens. Geographical miss, a
      major reason for recurrence of in-stent restenosis after brachytherapy, can be
      reduced by an improved radiation technique. The first preliminary data on drug
      eluting stents, showing only minimal neointimal proliferation at 6-month
      postimplantation, could represent a major breakthrough in the quest to solve
      restenosis.

PMID- 12053378
TI  - Stenting of bifurcation lesions: a rational approach.
AB  - The occurrence of stenosis in or next to coronary bifurcations is relatively
      frequent and generally underestimated. In our experience, such lesions account
      for 15%-18% of all percutaneous coronary intervention > (PCI). The main reasons
      for this are (1) the coronary arteries are like the branches of a tree with many
      ramifications and (2) because of axial plaque redistribution, especially after
      stent implantation, PCI of lesions located next to a coronary bifurcation almost
      inevitably cause plaque shifting in the side branches. PCI treatment of coronary
      bifurcation lesions remains challenging. Balloon dilatation treatment used to be
      associated with less than satisfactory immediate results, a high complication
      rate, and an unacceptable restenosis rate. The kissing balloon technique resulted
      in improved, though suboptimal, outcomes. Several approaches were then suggested,
      like rotative or directional atherectomy, but these techniques did not translate
      into significantly enhanced results. With the advent of second generation stents,
      in 1996, the authors decided to set up an observational study on coronary
      bifurcation stenting combined with a bench test of the various stents available.
      Over the last 5 years, techniques, strategies, and stent design have improved. As
      a result, the authors have been able to define a rational approach to coronary
      bifurcation stenting. This bench study analyzed the behavior of stents and
      allowed stents to be discarded that are not compatible with the treatment of
      coronary bifurcations. Most importantly, this study revealed that stent
      deformation due to the opening of a strut is a constant phenomenon that must be
      corrected by kissing balloon inflation. Moreover, it was observed that the
      opening of a stent strut into a side branch could permit the stenting, at least
      partly, of the side branch ostium. This resulted in the provocative concept of
      "stenting both branches with a single stent." Therefore, a simple approach is
      currently implemented in the majority of cases: stenting of the main branch with
      provisional stenting of the side branch. The technique consists of inserting a
      guidewire in each coronary branch. A stent is then positioned in the main branch
      with a wire being "jailed" in the side branch. The wires are then exchanged,
      starting with the main branch wire that is passed through the stent struts into
      the side branch. After opening the stent struts in the side branch, kissing
      balloon inflation is performed. A second stent is deployed in the side branch in
      the presence of suboptimal results only. Over the last 2 years, this technique
      has been associated with a 98% angiographic success rate in both branches. Two
      stents are used in 30%-35% of cases and final kissing balloon inflation is
      performed in > 95% of cases. The in-hospital major adverse cardiac events (MACE)
      rate is around 5% and 7-month target vessel revascularization (TVR) is 13%.
      Several stents specifically designed for coronary bifurcation lesions are
      currently being investigated. The objective is to simplify the approach for all
      users. In the near future, the use of drug-eluting stents should reduce the risk
      of restenosis.

PMID- 12053380
TI  - Pathobiology of coronary stents.

PMID- 12053381
TI  - Intracoronary beta radiation: state of the art.
AB  - This state-of-the-art review is intended to explore the development of beta
      radiation including catheter delivered and permanent implants from its inception
      to current practice. Specific focus will be given to the isotopes currently
      available, radiation physics of beta emitters, preclinical studies, clinical
      trials, beta radiation delivery systems, and implications for future practice.
      The encouraging results from the clinical trials have established vascular
      brachytherapy as a standard of care for patients with in-stent restenosis.
      Vascular brachytherapy requires additional "fine-tuning" to achieve full
      optimization.

PMID- 12053382
TI  - Chronic total occlusions: experience with fiber-optic guidance technology-
      optical coherence reflectometry.
AB  - Chronic total occlusions are difficult to treat and continue to challenge the
      interventional cardiologist. The primary difficulty is safely crossing the total
      occlusion with a guidewire before any revascularization can begin. One of the
      main reasons conventional and newer guidewires have not proven effective is
      simply the lack of visualization to safely steer the guidewire across the
      occlusion. This limitation can be overcome with new technology using a "forward
      looking" fiber-optic guidance. The Safe-Steer TO (Total Occlusion) Crossing
      System is a new guidance system that uses optical coherence reflectometry to
      steer a guidewire through total occlusions. Optical coherence reflectometry uses
      algorithms to determine tissue types (plaque vs arterial wall) by measuring the
      intensity of the reflection of near-infrared light. The authors' clinical
      experience with the Safe-Steer System has met considerable success. With their
      initial 28 patients (7 women, 21 men) with known chronic total occlusions and
      confirmed ischemia, the primary success rate for the crossing the occlusion was
      86% (24/28 cases). The average occluded lesion length was 41.1 +/- 30.8 mm. Our
      initial clinical experience demonstrates that the optical guidewire is a viable
      technology in the treatment of chronic total occlusions.

PMID- 12053383
TI  - Carotid stenting: which stent for which lesion?
AB  - Dedicated catheter and stent systems for use in the carotid circulation have only
      been developed recently. Almost exclusively, self-expandable metallic stents are
      being used. Longitudinal flexibility, contourability of the luminal
      configuration, sufficient radial resistive force, narrow meshwork for sealing of
      the diseased vessel wall, low profile of the constraint stent, and compatibility
      of the devices with routine angioplasty techniques are the premier requirements.
      Most of the current experience is based on the longitudinal wire mesh design
      (Carotid Wallstent). The narrow meshwork has excellent sealing capacity but the
      inherent (yet manageable) problem of foreshortening with expansion needs
      attention. The segmented ring designs of the more recent Nitinol stents permit
      more precise positioning and contouring of the luminal surface, yet their
      capacity to seal a complex or thrombotic lesion and their clinical safety needs
      further evaluation. As more distinct features of dedicated carotid stents are
      being developed and as their differential importance gets recognized, a more
      meaningful and individual stent selection for the carotid anatomy may further
      improve clinical outcome.

PMID- 12053384
TI  - Carotid artery stenosis: who should undergo surgery and who should undergo
      stenting?
AB  - Carotid angioplasty and stent implantation is a rapidly evolving treatment option
      currently under evaluation in several randomized trials. Although this technique
      needs some special technical skills and knowledge, it is technically simpler than
      many other interventional procedures. Current data indicate that the results
      regarding success rate and complication rate may be similar to surgery. It will
      take years to get the results of the randomized trials that are currently planed
      or have already started. Unfortunately, the results of these studies will not
      reflect the state-of-the-art because new stents and new protection devices will
      become available during these studies. Therefore, in clinical practice the
      decision has to be made depending on individual patient and lesion
      characteristics. Patients with concomitant diseases considered to be a risk
      factor for surgical procedures and patients with contralateral occlusion may be
      better candidates for angioplasty and stenting. However, patients with diffuse
      disease of the common carotid artery and patients with difficult vascular access
      may be better candidates for surgery.

PMID- 12053385
TI  - Peripheral vascular disease: perspectives on aortoiliac, renal, and femoral
      treatments using catheter-based techniques.
AB  - The percutaneous treatment of peripheral vascular disease has advanced over the
      past two decades and is fast becoming the preferred treatment of choice. Stents
      have positively altered the clinical outcomes in peripheral revascularizations.
      Anatomic variability is an important factor in determining if the patient is an
      ideal percutaneous interventional candidate. Future technological developments in
      percutaneous interventions will help include new patients with peripheral
      vascular disease previously considered nonideal percutaneous candidates.

PMID- 12053387
TI  - Aortic coarctation and recoarctation: to stent or not to stent?

PMID- 12053386
TI  - Identification of hemodynamically significant restenosis after percutaneous
      transluminal coronary angioplasty in acute myocardial infarction by
      transesophageal dobutamine stress echocardiography and comparison with myocardial
      single photon emission computed tomography.
AB  - BACKGROUND: Beside thrombolysis, percutaneous transluminal coronary angioplasty
      (PTCA) has become a well-established treatment for acute myocardial infarction.
      However, restenosis occurs in approximately 15%-40% of patients. Despite a
      frequently occurring infarct-related regional systolic dysfunction at rest, the
      identification of hemodynamically relevant restenosis seems important in terms of
      risk stratification, adequate treatment, and possible improvement of prognosis in
      these patients. This study was designed to assess the role of transesophageal
      dobutamine stress echocardiography and myocardial scintigraphy for identification
      of hemodynamically significant restenosis after PTCA for acute myocardial
      infarction. METHODS: Multiplane transesophageal stress echocardiography
      (dobutamine 5, 10, 20, 30, and 40 micrograms/kg per min) studies and myocardial
      single photon emission computed tomography (SPECT) studies were performed in 40
      patients, all of whom underwent PTCA in the setting of acute myocardial
      infarction > or = 4 months prior to the test. Repeated coronary angiography was
      performed in all study patients who showed stress-induced perfusion defects or
      wall-motion abnormalities, or both. RESULTS: Significant restenosis (> or = 50%)
      was angiographically found in 15 (37.5%) of 40 patients. Of these 15 patients,
      transesophageal dobutamine stress echocardiography identified restenosis in 12
      (80%) and myocardial SPECT in 14 (93%), yielding diagnostic agreement in 70% of
      patients. Echocardiographic detection of restenosis was based mainly on a
      biphasic response to increasing doses of dobutamine. Sensitivity and specificity
      for identification of hemodynamically relevant restenosis in individual patients
      was 80% and 92%, respectively for dobutamine stress echocardiography versus 93%
      and 68% for myocardial SPECT. CONCLUSIONS: Both transesophageal dobutamine stress
      echocardiography and myocardial SPECT were highly sensitive in identifying
      significant restenosis after PTCA for acute myocardial infarction. Therefore,
      either test, as a single diagnostic tool or especially if performed together, are
      clinically valuable alternatives to coronary angiography for the detection of
      restenosis after PTCA for acute myocardial infarction.

PMID- 12053388
TI  - Catheter closure of coronary artery fistulas.
AB  - Coronary artery fistulas are rare and vary widely in their morphological
      appearance and presentation. This paper presents experience of catheter closure
      of coronary artery fistulas in 40 patients. Catheter closure was performed with a
      variety of techniques, including detachable balloons, stainless steel coils,
      controlled-release coils, controlled-release patent ductus arteriosus (PDA)
      coils, and Amplatzer PDA plug. The vast majority of the fistulas were occluded
      with coils and in particular, controlled-release coils. Successful occlusion of
      the fistula was achieved in 39 (97%) of 40 patients. In one patient, the
      detachable balloon deflated prematurely and the patient underwent elective
      surgery. One 4-month-old infant died approximately 6 hours after the procedure.
      Immediate occlusion of the coronary artery fistula occurred in 33 (82%) of
      patients and late occlusion in 4 patients. Thus overall, total occlusion was
      achieved in 37 (97%) of 39 patients. The main complication was embolization of
      the occlusion device, which occurred in 6 (17%) of cases. In one of these cases,
      a detachable balloon deflated prematurely, and in five patients, coils embolized
      and were retrieved. In one of the patients, all six coils embolized 24 hours
      after the procedure but were retrieved, and further coils were implanted
      successfully. Controlled-release coils have made an important contribution to the
      technique of catheter closure of coronary artery fistulas. Catheter closure of
      these fistulas is an acceptable alternative to the standard surgical treatment.

PMID- 12053389
TI  - Experimental preseeding of the STARFlex atrial septal occluder device with
      autologous cells.
AB  - Devices used in interventional cardiology are permanent implants. However, most
      of the devices fulfill only a temporary function. For example, atrial septal
      defect (ASD) occluders serve as mechanical shields until complete in- and
      overgrowth of the occluding device by endogenous tissue from the defect edges has
      occurred. Thereafter, the foreign body material of the devices is no longer
      needed and bears potential long-term adverse effects. The concept of
      "biodegradable" occluder devices that act as transient mechanical shields to
      close the defects and as scaffolds for overgrowth with autologous tissue is,
      therefore, tempting. Since rapid and complete ingrowth as well as coverage by
      firm tissue is a prerequisite for any such "biological" occluder devices, the
      feasibility and short-term in vivo response to STARFlex devices preceeded with
      autologous cells was studied in an experimental sheep model. The experiments
      demonstrated that autologous cell preceeding of cardiovascular implants is
      technically feasible. Cells survived the mechanical stress of device
      implantation. A precoating of conventional STARFlex occluders led to an increased
      cellular density after cell seeding of the device, an increased resistance of the
      precultured cytolayer against mechanical stress, and a significantly higher
      poststress viability of "implanted" cells. Experimental closure of ASD using
      autologous-cell preseeded STARFlex devices was uncomplicated. In the sheep model
      this led to rapid, complete, and firm ingrowth of the device into the adjacent
      atrial tissue. A thicker layer of young fibrous granulation tissue in
      organization was found on the preceeded devices compared with the unseeded
      control group after 4 weeks in vivo. Currently, an increased thrombogenicity
      limits in vivo application.

PMID- 12053390
TI  - Interventional occlusion of congenital vascular malformations with the detachable
      Cook coil system.
AB  - INTRODUCTION: Nonsurgical closure of pathologic vascular communications can be
      achieved by coil embolization. Different systems used in patients with congenital
      heart disease (e.g., patent ductus arteriosus) allow controlled release of the
      devices. However, they are too stiff for coil occlusion of small or tortuous
      vessels. METHODS AND PATIENTS: The new detachable Cook coil system combines
      flexibility with a simple release control mechanism. Five children, age 8 days to
      10 years, underwent heart catheterization for interventional occlusion of
      different vascular malformations (two coronary artery fistulas, two
      aortopulmonary collaterals, and one hemangioma). The diameter of the vessels
      varied between 1.8 mm and 3.6 mm and the length between 10 mm and 22 mm. RESULTS:
      Up to four 0.018" soft spiral coils were placed as distally as possible in the
      feeding vessels. In addition, in two patients, one to three J-shaped coils were
      placed inside and proximal to spiral coils. Positioning of the coils was
      controlled easily by radio-opaque markers. Counter-clockwise rotation of the
      delivery wire provided fast and safe detachment without movement of the detached
      coils. Control angiograms showed complete occlusion of the vessels within 10
      minutes after delivery of coils. CONCLUSION: Interventional closure of vascular
      malformations can be successfully obtained with the detachable Cook coil system.
      This system offers safe and controlled placement of coils, and it works rapidly
      in an uncomplicated manner.

PMID- 12053391
TI  - Transcatheter closure of atrial septal defects with the STARFlex device: early
      results and follow-up.
AB  - BACKGROUND: The STARFlex (SF) device is a CardioSEAL (CS) double-umbrella device
      that has been modified by the addition of a self-centering mechanism comprised of
      nitinol springs connected between the two umbrellas and a flexible core wire with
      a pin-pivoting connection. This paper compares the results of atrial septal
      defect (ASD) closure with CardioSEAL and STARFlex devices. PATIENTS AND METHODS:
      Between December 1996 and March 2000, 117 patients underwent ASD closure with
      CardioSEAL (n = 79) and STARFlex (n = 38). The mean age (17 years), weight (49
      kg), and ASD size (15 mm) were similar in the two groups. The procedures were
      performed under general anesthesia with both fluoroscopic and transesophageal
      echocardiographic monitoring. IMMEDIATE RESULTS: The devices were successfully
      implanted in all patients. Ten patients had multiple ASDs. A single device was
      used in four patients (CardioSEAL in three, STARFlex in one), while a
      simultaneous placement of two CardioSEAL (one patient) or two STARFlex (five
      patients) were performed in six patients. The results are summarized as follows:
      [table: see text] Follow-Up Results: On follow-up clinical exam,
      electrocardiograms, chest X-rays, and echocardiograms were obtained at 1, 6, and
      12 months. [table: see text] During follow-up there were no deaths, endocarditis,
      rhythm disturbances, or other complications. Arm fractures were observed almost
      exclusively with large CardioSEAL devices (40 mm, less frequently with 33 mm),
      and only in one 33-mm STARFlex device. There were no clinical complications
      related to fractures. CONCLUSIONS: The STARFlex device seems to offer better
      results than the CardioSEAL, with significantly lower rates of residual shunts
      and arm fractures.

PMID- 12053392
TI  - Occlusion of interatrial communications with the Amplatzer device: experience in
      48 consecutive patients.
AB  - Both secundum atrial septal defect (ASD) and patent foramen ovale (PFO) have been
      closed interventionally using several different occluding devices. At a single
      institution we strived for interventional occlusion of interatrial communications
      using the Amplatzer device exclusively. During a study period of 22 months, we
      studied 48 patients ranging in age from 1 to 48 years with an ASD (n = 45) or a
      PFO (n = 3). Successful implantation of an Amplatzer device was possible in 92%
      of the patients, and 95% of these patients had a complete early closure of their
      defect. There were no complications related to the procedure. We conclude that
      interventional closure of interatrial communications with the Amplatzer device is
      feasible and safe for selected patients.

PMID- 12053393
TI  - Catheterization of the adult with congenital heart disease (ACHD): beyond
      "shooting the coronaries".

PMID- 12053394
TI  - Echocardiography before, during, and after interventions.
AB  - Before intervention, a detailed echocardiographic examination is mandatory for
      the decision whether this procedure will be necessary, possible, and safe. During
      intervention, transesophageal echocardiography (TEE) is needed for the continuous
      monitoring of the procedure, immediate assessment of results, and complications.
      TEE results in a significant reduction of fluoroscopy time. After intervention,
      echocardiography provides information on long-term results and newly developed
      complications.

PMID- 12053395
TI  - Critical pulmonary stenosis.
AB  - Critical pulmonary stenosis causes cyanosis and can be potentially lethal in the
      neonate. Initial treatment includes general resuscitation and infusion of
      prostaglandin E1 to dilate the ductus. The diagnosis is usually made
      echocardiographically, but a right ventriculogram in the outflow tract may be
      necessary in some patients with only a tiny valve opening. Preformed catheters
      may aid in the passage of an appropriate guidewire. Valvuloplasty should be
      performed with a balloon approximately 1.2 times the annulus diameter. Most
      patients remain mildly to moderately cyanotic immediately after the procedure.
      With right ventricular (RV) growth and improved RV compliance, the cyanosis
      eventually resolves. Some patients may require prolonged prostaglandin infusion,
      a surgical shunt, or other mechanical means of maintaining systemic-to-pulmonary
      artery flow. Intermediate--to long-term results are excellent. However, only 5%
      10% of patients may require surgical relief of residual valve or subvalvular
      stenosis. Very long-term follow-up raises concern about the significance of
      induced pulmonary insufficiency. Up to 30% of patients may require repeat balloon
      valvuloplasty.

PMID- 12053396
TI  - Issues in transcatheter treatment of critical aortic stenosis in the newborn
      infant.
AB  - Critical aortic valve stenosis is not a frequently seen disease. In most cases,
      these patients are in critical condition. Transcatheter dilatation is one of the
      therapeutic options for treatment. This article addresses important issues in
      transcatheter dilatation in the newborn infant.

PMID- 12053397
TI  - Intervention in the critically ill neonate and infant with hypoplastic left heart
      syndrome and intact atrial septum.
AB  - Neonates that present with hypoplastic left heart syndrome (HLHS) and intact
      atrial septum (IAS) pose a major management problem for the pediatric cardiac
      team. They are critically ill newborns with profound hypoxemia and acidosis that
      require immediate attention. Controversy exists as to the most appropriate
      management strategy. In one series where a primary and emergent surgical-staged
      reconstructive procedure was performed, the in-house hospital mortality was 65%
      and the overall survival was 17%. With equal abysmal results, transcatheter
      creation of an atrial septal defect (ASD) using conventional balloon atrial
      septostomy (BAS) with or without the combination of blade atrial septotomy had an
      unacceptable high risk of cardiac perforation leading to tamponade and death.
      However, using more modern transcatheter techniques of transseptal perforation of
      the atrial septum followed by progressive and serial balloon septoplasty,
      creating an ASD, significantly reduced the risk of the procedure. In one series,
      16 consecutive neonates underwent this type of interventional procedure without
      procedural mortality. The management strategy of creating an ASD in the
      catheterization lab followed by Stage I reconstructive surgical repair 3-5 days
      after the initial catheterization procedure improved the in-house survival to
      57%. Unfortunately, there continues to be significant attrition of these patients
      undergoing Stage II and III reconstructive repair, which supports cardiac
      transplantation as an alternative strategy. There have been echocardiographic and
      histopathologic studies of these neonates, and an important echo classification
      of left atrial morphology has been described with perhaps some prognostic
      implication. In addition, autopsy specimens have demonstrated significant
      "arterialization" of the pulmonary venous architecture that likely dooms the
      patient with single ventricle physiology to a poor outcome. Future improvement in
      transcatheter techniques and materials offer promise in palliating these
      critically ill neonates. The concept of radiofrequency energy perforating
      catheters has great merit and may reduce the risk of cardiac perforation as
      compared with the rigid and long transseptal needle. Echocardiographic imaging at
      the time of entry through the IAS may improve the safety as well. The novel
      concepts of "butterfly" or "dog-bone" stents placed across the atrial septum
      creates a precisely sized ASD that may be more conducive to effectively lower
      left atrial hypertension, yet avoids excessive pulmonary blood flow associated
      with large atrial communications. In addition, new materials, such as the Cutting
      Balloon Catheter, may offer promise in creating ASDs in these patients. A more
      aggressive approach would be to consider intrauterine fetal transcatheter opening
      of the IAS using modified techniques that have been attempted for left
      ventricular outflow tract obstruction. Unfortunately to date, the results of
      attempted relief of aortic valve stenosis have been extremely poor. Finally, we
      as interventionalists need to continue to improve our skills to help in the
      complex management of these critically ill neonates and infants. Only through
      continued efforts of the entire cardiac team of intensivists, cardiologists,
      cardiothoracic surgeons, and interventionalists will our management strategy be
      defined to maximize the future outcome in this group of patients.

PMID- 12053398
TI  - Comprehensive management of branch pulmonary artery stenosis.
AB  - Branch pulmonary artery stenosis may occur as an isolated finding or in
      conjunction with other cardiac malformations; it may be congenital or acquired
      postoperatively. Transcatheter management with balloon pulmonary angioplasty
      (BPA) and/or endovascular stenting is generally considered the procedure of
      choice for most patients. With the introduction of high-pressure balloons, the
      results of BPA have improved significantly (75%). Stent implantation has
      increased the success rate to over 90%. However, BPA continues to be the initial
      procedure of choice for distal stenoses, or those associated with branching
      points, and in small children or infants. Stent implantation is preferred over
      BPA for central or proximal stenoses, and those due to kinking or tenting,
      external compression, intimal flaps, failed balloon dilation, and early
      postoperative procedures. Certain lesions, such as supravalvar pulmonary
      stenosis, or stenosis at the branch pulmonary arteries bifurcation, are better
      dealt with at surgery. High-risk situations for the development of postoperative
      pulmonary artery (PA) stenosis exist in small infants with hypoplastic branch PAs
      after a conotruncal procedure, after duct ligation, after shunt insertion, after
      PA band placement, or after pulmonary arteriotomies or anastomoses of any kind. A
      combined collaborative transcatheter and surgical approach is essential for many
      patients with PA stenosis, particularly in complex forms of tetralogy of Fallot.

PMID- 12053399
TI  - Collaborative approach in the management of pulmonary atresia with intact
      ventricular septum.

PMID- 12053400
TI  - Vascular access, vessel thrombosis, vessel reconstruction.

PMID- 12053401
TI  - [Clinical pharmacology and clinical evaluation of drugs. Significance and
      progress].

PMID- 12053402
TI  - [Development of clinical drug trials and the formal, legal and financial scope].

PMID- 12053403
TI  - [Drug safety and post-marketing control. Developments since the reform of the
      1978 drug regulation].

PMID- 12053404
TI  - [The Therapeutic Drug Committee of German Physicians. 50 years in the service of
      drug safety in Germany].

PMID- 12053405
TI  - [End points of clinical studies: surrogate parameters of "hard clinical end
      points"?].

PMID- 12053406
TI  - [Responsibilities of coordination centers for clinical studies and their status
      in general practice].

PMID- 12053407
TI  - [Status of pharmacogenomics and its future role in drug therapy].

PMID- 12053408
TI  - [Drug prescription studies. Goals and results].

PMID- 12053409
TI  - [Spondyloarthritis].

PMID- 12053410
TI  - [30-year-old patient with exanthema mostly of the trunk and granulomatous
      hepatitis].

PMID- 12053411
TI  - [37-year-old patient with eye muscle paralysis and rapidly progressing
      respiratory insufficiency].

PMID- 12053412
TI  - [Rational and cost effective osteoporosis prevention and therapy].

PMID- 12053413
TI  - [Fludarabine as primary therapeutic drug in chronic lymphatic leukemia].

PMID- 12053414
TI  - National Institute for Clinical Excellence (NICE): symposium on technology
      assessment.

PMID- 12053415
TI  - Health technology assessment for the NHS in England and Wales.
AB  - In healthcare decision making, there is an important functional separation
      between assessment and appraisal. In the U.K. National Health Service (NHS), this
      distinction is illustrated by the separation of roles between the Health
      Technology Assessment Programme and the National Institute for Clinical
      Excellence. However, it can be seen at every level within the healthcare system.
      Assessment of a technology is a scientific task that synthesizes all relevant
      evidence on effectiveness and cost-effectiveness; its results are therefore
      generalizable. Appraisal of the technology is informed by the assessment but adds
      context-specific judgments on the applicability of the evidence, the feasibility
      and impact of alternative options, relative priorities, and wider social and
      ethical aspects. An explicit distinction between assessment and appraisal is
      helpful in achieving clarity, consistency, and consensus. It also makes clear the
      need for a wide range of assessment reviews to support decision making by
      commissioners, providers, and users of health services. Increasingly, the
      secondary research supported by the NHS R&D Programme is being distributed
      electronically. It is also being used to identify areas in which further primary
      research should be commissioned.

PMID- 12053416
TI  - National Institute for Clinical Excellence (NICE).  HTA rhyme and reason?
AB  - The technology appraisal program of the National Institute for Clinical
      Excellence (NICE) was established on April 1, 1999. Its role is to advise the NHS
      in England and Wales on the clinical effectiveness, cost-effectiveness, and
      service impact of new and emerging as well as established healthcare
      technologies. This paper describes the role of HTA in the NICE technology
      appraisal process, discusses some of the challenges of the use of HTA in national
      policy making, and considers some of the potential ways forward.

PMID- 12053417
TI  - Development of health technology assessment in Europe. A personal perspective.

PMID- 12053418
TI  - Health technology assessment. The pharmaceutical industry perspective.
AB  - Increasingly, health technology assessment (HTA) is used to aid decisions on the
      reimbursement of pharmaceuticals or recommendations for their use. The
      pharmaceutical industry seeks to work in partnership with HTA agencies; however,
      this presents a number of challenges. Clinical trials will need to include
      appropriate measures that capture economic and patient benefits as well as
      relevant clinical endpoints, and the industry will want to seek international
      harmonization of the many guidelines for economic evaluation. The problem of
      demonstrating cost-effectiveness of a product before it is available for use must
      be addressed, possibly by conditional reimbursement to allow collection of real
      world evidence. It is also important that reimbursement decision makers minimize
      bias, play fair, and adhere to the written rules they issue. If the industry
      fairly demonstrates the value of a product using the best available evidence, HTA
      agencies should be transparent in the rationale for their recommendations.

PMID- 12053419
TI  - Health technology assessment in the United States. Past, present, and future.

PMID- 12053420
TI  - Challenges, choices, and Canada.
AB  - The Canadian Coordinating Office for Health Technology Assessment (CCOHTA) was
      established by the Federal, Provincial, and Territorial Ministers of Health in
      1989 for a 3-year trial period. In 1993 CCOHTA was made a permanent organization
      and in 1999 the Deputy Ministers of Health renewed CCOHTA's mandate and increased
      its funding. CCOHTA's role is to coordinate health technology assessment (HTA)
      priorities across jurisdictions, foster and undertake assessment activity, and
      function as a clearinghouse for technology assessment results while increasing
      healthcare system stakeholder awareness of HTA findings. The coordinated and
      collaborated approach adopted by CCOHTA minimizes duplication with other national
      and provincial organizations and contributes to the ability of the Canadian
      healthcare system to continue to deliver high-quality health care to its
      constituents.

PMID- 12053421
TI  - Antipodean assessment. Activities, actions, and achievements.

PMID- 12053422
TI  - Executive summary of the ECHTA/ECAHI project. European Collaboration for Health
      Technology Assessment/Assessment of Health Interventions.

PMID- 12053423
TI  - Summary report of the ECHTA/ECAHI project. European Collaboration for Health
      Technology Assessment/Assessment of Health Interventions.

PMID- 12053424
TI  - Health promotion and disease prevention as a complement to community health
      indicators. Working group 1.

PMID- 12053425
TI  - Systems for routine information sharing in HTA. Working group 2 report.

PMID- 12053426
TI  - European joint assessments and coordination of findings and resources. Working
      group 3 report.

PMID- 12053427
TI  - Best practice in undertaking and reporting health technology assessments. Working
      group 4 report.

PMID- 12053428
TI  - Education and support networks for assessment of health interventions. Working
      group 5 report.

PMID- 12053429
TI  - Health technology assessment in policy and practice. Working group 6 report.

PMID- 12053430
TI  - Restoration of upper extremity function after peripheral nerve injuries.
AB  - These days injuries to the peripheral nerves of the upper extremity that
      necessitate total or partial lesion are very common in the household and working
      environment. With regard to the majority of these injuries, not only plastic
      surgeons or neurosurgeons must have knowledge  of their correct treatment, but
      general surgeons as well. The principles of reconstruction of the peripheral
      nerves of the upper extremity are described. The authors refer to immediate and
      delayed nerve repair, free nerve grafting, free vascularised nerve grafting,
      tendon transfer for a paralyzed hand, pedicled muscle transfer, functioning free
      muscle transplantation and neurotization.

PMID- 12053431
TI  - Topigel in the treatment of hypertrophic scars after burn injuries.
AB  - The authors present the results of a medium-term study in which they investigated
      the therapeutic effect of the silicone elastomer TopiGel on developing
      hypertrophic scars in a group of patients after burn injuries classified as IIb
      or deeper. The hitherto published results are very encouraging. This medium-term
      study confirmed the hypothesis that TopiGel has a positive effect on the
      reduction, stabilization and normalization of hypertrophic scars. In 48 patients
      (96%) out of a total of 50, stabilization of the scar occurred as well as its
      functional and cosmetic normalization, although the subjective view of the
      patients or parents (in case of pediatric patients) differed in some instances.
      In two children (4%) only a significant reduction of the scar occurred and not
      normalization, due to incorrect application of the gel by the parents, lack of
      adherence to basic hygienic principles or the recommended procedure of gel
      application. In case of repeated complications, treatment was not pursued. In two
      patients (4%) treatment was discontinued for a short time due to an allergic skin
      reaction subsequently, treatment was resumed until complete stabilization of the
      scar was achieved. The study ruled out a positive therapeutic effect of the
      silicone sheet on the painfulness of a scar and old, mature hypertrophic scars.

PMID- 12053432
TI  - New safety assurance for biological skin covers.
AB  - The described system of safety assurance of cryopreserved allogeneic and
      xenogeneic dermoepidermal transplants comprises serological examination of
      deceased tissue donors, long-term storage of sera of all donors, microbiological
      control of prepared allogeneic and xenogeneic dermoepidermal grafts, labelling of
      released tissue grafts and monitoring of temperatures inside the mechanical
      freezer (-80 degrees C). From a total number of 76 donors from whom tissues were
      collected for transplantation during 1999-2001, tissues were discarded in two
      instances. One because of a positive HBsAg test, the others second one because of
      presence of anti-HTLV antibodies. In xenogeneic dermoepidermal grafts, out of a
      total number of 1,203 grafts prepared during the same period, 84 (6.9%) were
      discarded because of the presence of pathogeneic or potentially pathogeneic
      microbes. The system of labelling released grafts makes unequivocal
      identification of the pathway from recipient to donor possible, while at the same
      time respecting the anonymous character of the donor's data. In xenogeneic grafts
      it ensures the identification of the appropriate batch. Storage of cryopreserved
      biological skin covers at a temperature of -80 degrees C in low temperature
      cabinets with emergency back-up cooling with liquid nitrogen and a supplementary
      source of electric power, proved very useful. The system responds to the gradual
      implementation of the principles of Quality Management System ISO 9000 and Good
      Manufacturing Practice into the activities of tissue banks. Further tightening of
      the demands for the safety of allo- and xeno-transplantation is foreseen in
      conjunction with the occurrence of transmissible spongiform encephalopathy and
      porcine retroviruses.

PMID- 12053433
TI  - Polythelia is not a mere aesthetic issue.
AB  - Anomalies in breast development include an increase in the number of breast
      (polymastia), nipples (polythelia), areolas (polythelia areolaris) and the tissue
      of the breast gland. Of the many forms, the most common is an accessory nipple,
      polythelia. It commonly develops along the embryonic "milk line" (Fig. 1). It
      constitutes a diagnostic problem only sporadically. Excision is indicated for
      diagnostic, treatment or cosmetic reasons. In the literature, the evidence of
      these anomalies suggests that they could be markers for others, most notably
      urologic malformations and malignancies.

PMID- 12053434
TI  - Ensuring prehospital care in thermal injuries: experience from an explosion in a
      textile factory.
AB  - The objective of this work was to inform about the performance of the rescue
      service, in collaboration with other members of an integrated rescue system, in
      responding to an event in which several subjects suffered burn injuries. Proper
      organization of the work by a doctor of the rescue group at the site of the
      explosion, the work of the rescue service dispatchers, and the coordination of
      the activities of the different rescue teams are the prerequisite for the
      successful avoidance of the sequelae of mass disasters.

PMID- 12053435
TI  - Advantages and disadvantages of endoscopically assisted front-lift.
AB  - Reduced surgical risk, a diminution of visible scars, rapid recovery, long-termed
      results and reduced costs are at present the most important demands on
      development in aesthetic plastic surgery. Endoscopically assisted front-lift
      meets perfectly the need of reduced invasiveness. It is technically simple and
      associated with a minimum of complications. It brings minimal scars beyond the
      hairline with a favourable effect after eliminating the drop of the brows, and
      wrinkles on the forehead. The duration of the effect in the aging face depends,
      however, similarly as other methods, on the characteristics of the skin, changes
      in other parts and the individual disposition. A marked disadvantage is the high
      initial, cost of special equipment. Their recovery ensues from the reduced time
      of surgery, reduced consumption of material, lower number of complications and
      more rapid return to normal life.

PMID- 12053436
TI  - Advertising content in physical activity print materials.
AB  - Copies of 80 sets of print materials available free of charge to the general
      public were analyzed to determine the relationship between the developer and
      advertising-related material. Almost all of the materials had some form of
      advertising content. Materials from commercial product vendors were most likely
      to have product logos, references to specific brands, and had the greatest number
      of logos, and the greatest number of references to specific brands. They were the
      second most likely to have advertising slogans, and had the second greatest
      number of advertising slogans.

PMID- 12053437
TI  - Ethnic and gender differences in smoking and smoking cessation in a population of
      young adult air force recruits.
AB  - PURPOSE: To examine gender and ethnic differences in smoking and smoking
      cessation in a population of young adult military recruits. DESIGN: A self
      administered survey of demographics, tobacco use, and other health risk behaviors
      was administered at the start of basic military training. SETTING: The study was
      conducted at Lackland Air Force Base, San Antonio, Texas, where all U.S. Air
      Force recruits complete basic military training. SUBJECTS: All recruits who
      entered the U.S. Air Force between September 1995 and September 1996 participated
      in this study (n = 32,144; 100% participation rate). MEASURES: Recruits completed
      a written 53-item behavioral risk questionnaire. Measures examined in the present
      study included smoking status (ever having smoked a cigarette, current daily
      smoking, and quitting); demographics (ethnicity, gender, education, family
      income, and age); smoking history; and nicotine dependence. RESULTS: Rates of
      ever smoking, current daily smoking, and quitting were examined in multiple
      logistic regression analyses as a function of gender and ethnicity, controlling
      for age, education, and family income. Overall, 54% of recruits had ever smoked a
      cigarette and 24.9% smoked daily at the time of entry into basic military
      training. Smoking rates were highest among white and Native American recruits.
      Among whites, women were more likely to be a current daily smoker (31.6% vs.
      29.4%; odds ratio [OR] = 1.18, 99% confidence intervals [CI] = 1.08-1.29). The
      opposite pattern was observed among African-Americans (5.6% vs. 9.8%,
      respectively; OR = .57; CI = .41-.79). Current smokers had low levels of nicotine
      dependence compared with the general population of U.S. smokers, but whites
      tended to be more dependent than other ethnic groups. Cessation rates were
      similar for men and women but differed according to ethnicity, ranging from 15%
      among whites to 23% among Hispanics. CONCLUSIONS: These findings document
      important gender and ethnic differences in cigarette smoking among military
      recruits. Whites and Native Americans were more likely to smoke, less likely to
      quit, and more nicotine-dependent than other ethnic groups. Across
      gender/ethnicity groups, smoking rates were especially high among white women,
      with nearly one-third smoking daily until entry into basic training. Gender
      differences were not observed in cessation rates, but Hispanics were more likely
      than other ethnic groups to have quit smoking. The results highlight the need to
      develop effective cessation interventions for this population.

PMID- 12053438
TI  - Making youth tobacco control programs more ecological: organizational and
      professional profiles.
AB  - PURPOSE: To identify the organizational and professional correlates of the
      integration of the ecological approach in Canadian public health organizations'
      tobacco control programs for youth. DESIGN: Cross-sectional survey. SETTING:
      Canadian public health organizations. SUBJECTS: One hundred and ten tobacco
      control programs implemented in 90 organizations. The response rate for the
      organizations was 87%. MEASURES: Descriptions of programs were obtained by
      telephone interviews. An analytical procedure was applied to the program data to
      identify intervention settings, targets and strategies for each program. Using
      this information, a summary score of the integration of the ecological approach
      was estimated for each program. Organizational and professional variables were
      assessed by self-administered questionnaires to managers and professionals
      involved in these programs. RESULTS: The level of integration of the ecological
      approach in programs was related to organizational (frequency of contacts and
      collaborations with external partners, team composition) and extraorganizational
      factors (size of the city in which the public health unit is located). Cognitive
      attributes of the practitioners (knowledge and beliefs) also emerged as
      significant predictors. Finally, positive associations were observed between
      practitioners' personal characteristics (educational achievement, working status
      in health promotion [full vs. part-time], previous experience, gender, and
      disciplinary/professional background) and cognitive predictors. CONCLUSIONS:
      Organizational environment and staff preparation play a critical role in the
      adoption of the ecological approach in tobacco control programs.

PMID- 12053439
TI  - Construct validity of the stages of change of exercise adoption for different
      intensities of physical activity in four samples of differing age groups.
AB  - PURPOSE: To examine whether the stages of change of exercise adoption
      appropriately address strenuous, moderate, and mild intensities of physical
      activity. DESIGN AND SETTING: Secondary analysis of four data sets investigating
      transtheoretical model (TTM) constructs for exercise adoption. SUBJECTS: Four
      samples of differing age groups (adolescents, n = 400; college students, n = 240;
      adults, n = 346; seniors, n = 504). MEASURES: Stage of change algorithm for
      exercise adoption and self-reported physical activity. RESULTS: Multivariate
      analysis of variance (MANOVA) results showed that stages of change were
      distinguished by strenuous and moderate but not mild exercise in the adolescent,
      college student, and adult sample. In the senior sample, stage differences were
      found in the frequency of exercising (equivalent for moderate to strenuous
      exercise) and the frequency of walking (equivalent for mild exercise). Bivariate
      correlation coefficients as well as sensitivity, specificity, and related quality
      indices decreased respectively from strenuous to moderate to mild exercise and
      from exercising to walking. CONCLUSIONS: Results provide additional support for
      the construct validity of the stages of change for strenuous and moderate
      intensities of physical activity. Development of a new stage assessment
      instrument for mild intensities of physical activity is recommended. Limitations
      include use of a different validation measure of exercise behavior in the senior
      sample.

PMID- 12053440
TI  - Checklist of Health Promotion Environments at Worksites (CHEW): development and
      measurement characteristics.
AB  - PURPOSE: Health promotion policy frameworks, recent theorizing, and research all
      emphasize understanding and mobilizing environmental influences to change
      particular health-related behaviors in specific settings. The workplace is a key
      environmental setting. The Checklist of Health Promotion Environments at
      Worksites (CHEW) was designed as a direct observation instrument to assess
      characteristics of worksite environments that are known to influence health
      related behaviors. METHODS: The CHEW is a 112-item checklist of workplace
      environmental features hypothesized to be associated, both positively and
      negatively, with physical activity, healthy eating, alcohol consumption, and
      smoking. The three environmental domains assessed are (1) physical
      characteristics of the worksite, (2) features of the information environment, and
      (3) characteristics of the immediate neighborhood around the workplace. The
      conceptual rationale and development studies for the CHEW are described, and data
      from observational studies of 20 worksites are reported. RESULTS: The data on
      CHEW-derived environmental attributes showed generally good reliability and
      identified meaningful sets of variables that plausibly may influence health
      related behaviors. With the exception of one information environment attribute,
      intraclass correlation coefficients ranged from 0.80 to 1.00. Descriptive
      statistics on selected physical and information environment characteristics
      indicated that vending machines, showers, bulletin boards, and signs prohibiting
      smoking were common across worksites. Bicycle racks, visible stairways, and signs
      related to alcohol consumption, nutrition, and health promotion were relatively
      uncommon. CONCLUSIONS: These findings illustrate the types of data on
      environmental attributes that can be derived, their relevance for program
      planning, and how they can characterize variability across worksites. The CHEW is
      a promising observational measure that has the potential to assess environmental
      influences on health behaviors and to evaluate workplace health promotion
      programs.

PMID- 12053441
TI  - [Clinical picture and therapy of endometriosis].
AB  - This paper defines endometriosis disease and summarizes its clinical and
      pathological features. Definitive diagnosis of endometriosis requires direct
      visualization of the disease. Laparoscopy is the most commonly employed method to
      inspect the peritoneal cavity directly. We list the drugs employed for the
      medical therapy of endometriosis and put evidence on limits and side effects of
      medical treatment. The surgical treatment is mainly laparoscopic for excision or
      coagulation of pelvic endometriosis implants but frequently the rate of
      recurrences or new implants is high. In this paper we stressed the urological
      aspect of endometriosis in particular bladder and ureteral locations and the
      secondary ureteral injuries resulting from surgical treatment.

PMID- 12053442
TI  - ["Post-actinic pelvic disease" and the ureter: the post-actinic ureter].
AB  - PURPOSE: A retrospective study was done to analyze late urological complications
      following curative radiotherapy of primary gynecological carcinomas. METHODS:
      From 1990 to 2000, 167 patients with primary gynecological cancer treated with
      external radiotherapy or intracavitary applications were observed. During the
      follow-up, all signs, symptoms and therapy of late treatment complications were
      recorded. RESULTS: Most patients with ureteral stenosis or obstruction required
      surgical correction. Most patients with bladder fistulas were best served by
      creation of a cutaneous urinary diversion. CONCLUSION: Ureteral complications
      after radiotherapy of the pelvis are rare but severe. Surgical therapy of
      irradiated tissues has a higher complication rate compared to surgery on non
      irradiated tissue. A cutaneous urinary diversion may be an acceptable and safe
      procedure when the bladder is definitely compromised.

PMID- 12053443
TI  - [Treatment of ureteral lesions during gynecologic surgery].
AB  - Surgery of gynecologic area and of pelvic cavity in general is a risk situation
      for ureteral injury. The incidence of these injuries is about 1% and may be
      considered as "unavoidable", irrespective of the surgical approach which could be
      either abdominal, vaginal or laparoscopic. In this study, 37 patients who had
      undergone a previous gynecological surgery were assessed for 38 ureteral units.
      Ureteral injury was identified at the surgical table in 2 patients who were
      treated successfully during the same surgical session with an end-to-end
      anastomosis. In 8 patients, a double-J ureteral stent was placed and the cure was
      obtained in 7 patients. The single case of failure was converted to surgery. 22
      female patients for 23 ureteral units were subjected to open surgery performing
      16 ureterocystoneostomies, 6 of them with a combined psoas-bladder hitching. In 1
      patient a termino-terminal anastomosis was performed due to an injury in an upper
      site. Finally, in 3 patients nephrectomy was carried out due to a nonfunctional
      kidney; 1 patient refused surgery, whereas in another patient a spontaneous
      canalization of the excretory tract was obtained after reposition of a
      percutaneous nephrostomy. The minimum follow-up is of at least 1 year. The
      diagnostic aspects and therapeutic indications are then described with a special
      emphasis on the so-called prognostic factors which could influence the outcome of
      the treatment. Finally, the main surgical correction techniques employed in case
      of leakage of ureteral substance, are reviewed.

PMID- 12053444
TI  - [Pathology of the gynecologic ureter].
AB  - OBJECTIVE: Ureteral lesions due to pelvic endometriosis, gynecological surgery
      and post-actinic are common findings in urology. Pelvic endometriosis can also be
      caused by a direct or indirect ureteral lesion after laparoscopic procedures.
      Stenosing ureteral lesions can be found after major gynecological surgery and
      after laparoscopic procedures. Many surgical techniques have been described to
      reduce the risks and to correct the complications. MATERIALS AND METHODS: In our
      experience (1985-2000) we registered 2 ureteral lesions due to pelvic
      endometriosis. The patients were treated with resection and end-to-end
      anastomosis. We also protected the site of suture with omentoplasty. 49 patients
      developed a post-actinic ureteral lesion (43 unilaterally and 6 bilaterally). In
      20 cases we performed an end-to-end anastomosis, in 25 cases we re-implanted the
      ureter and in 10 cases we performed a psoas hitch. In 36 patients we performed an
      omentoplastic procedure. Ureteral lesions after gynecological surgery were
      registered in 44 patients (33 after trans-vaginal hysterectomy, 6 after
      colposuspension, 5 after Wertheim). 40 ureters underwent open air surgery (26
      patients, resection + end-to-end anastomosis, 6 patients simple re-implantation,
      4 psoas hitch). In 32 patients we performed an omentoplastic procedure. 4
      patients were corrected with an endoscopic procedure. These patients had a
      fulgurating lesion of the ureter with a consequent urinary fistula. A long-term
      drainage with endoureteral stent avoided the operation. All patients with an
      acute ureteral lesion were treated with a nephrostomic drainage and a short term
      repair. RESULTS: In 2 patients with ureteral lesions due to pelvic endometriosis
      the results after corrective operation (3-4 years follow-up) were excellent with
      a good conservation of kidney function. In patients that underwent operation due
      to post-actinic ureteral stenosis, long-term results were: 78% complete
      preservation of kidney function without the need for permanent stents, 20%
      preservation of kidney function with need to conserve endoureteral stents, 2%
      loss of kidney function and consequent nephrectomy. Long-term results in patients
      that underwent an operation for ureteral lesions following surgical gynecological
      procedures were: 87% complete preservation of kidney function without the need of
      permanent stents, 13% conservation of kidney function but no need to preserve the
      endoureteral stent. DISCUSSION: Lower urinary tract lesions after gynecological
      surgery are present in every surgical study. Most authors describe that
      intraoperative cystoscopy can immediately enhance the problem avoiding a re
      operation. The laparoscopic risk seems to be for the cardinal ligaments when they
      divide beneath the uterine veins. Most authors seem to agree with the immediate
      need for a nephrostomic drainage followed by a postponed intervention. These
      procedures seem to reduce morbidity and the risk for a re-operation. In extended
      ureteral lesions there is agreement that psoas hitch is the best procedure. In
      our experience a nephrostomic drainage and a postponed intervention (2 weeks) has
      given comparable results with the best in literature as far as kidney function is
      concerned. The worst results were registered in patients with chronic lesions and
      with a deteriorated kidney function at the moment of the corrective procedure.

PMID- 12053445
TI  - [The gynecologic ureter revisited].
AB  - From 1991 to 2001, 23 female patients were admitted to the Urologic Operative
      Unit of the Varese Hospital for urological lesions due to gynecological surgery.
      The mean age of the patients was 52 years. Out of them, 5 presented a complete
      division of the ureter after hysterectomy, 3 an inadvertently ligature of the
      ureter and 2 an angulation. In 12 cases a vesico-vaginal fistula was present,
      while a patient presented an uretero-vaginal fistula. The 5 patients with
      complete division of the ureter underwent: end-to-end anastomosis (3 patients);
      reimplantation (2 patients); psoas hitch (1 patient). In 3 patients with ureter
      ligation a reimplantation with psoas hitch was performed; in 2 cases with ureter
      angulation a double J stent was placed. The patient with an uretero-vaginal
      fistula underwent a reimplantation with psoas hitch while the patients with
      vesico-vaginal fistula were successfully treated by a combined transperitoneal
      and transvesical access, excision of the fistula tract and closure of the bladder
      and vaginal wall with omental interposition.

PMID- 12053446
TI  - [Pathology of the gynecologic ureter: our experience].
AB  - Endometriosis, surgery and radiotherapy are the main causes of ureteral injuries
      in gynaecologic pathology. MATERIALS AND METHODS: In this paper we present our
      experience about ureteral injuries. We treated 31 patients; 6 cases of
      endometriosis, 13 cases of pelvic radiotherapy for gynecologic tumors, 12 cases
      of ureteral injuries after gynecologic surgery. The treatments were different
      depending on the cause of the lesion and on the site of the lesion. In 3 cases we
      performed an ureteral-bladder implant with bladder psoas hitch, in 2 cases an end
      to end anastomosis was made. In 2 cases we made an ureteric substitution with
      Boari bladder flap. In 8 cases the ureteral stenting with DJ or a percutaneous
      nephrostomy was the solution. RESULTS AND CONCLUSIONS: In our experience good
      results can be obtained with ureteral implant and bladder psoas hitch. The end to
      end ureteral anastomosis had disappointing results in our hands. In case of
      ureteral fistula it would be better repair it as soon as possible. If the
      ureteral lesion is recognised during surgery and the loss of substance is not
      complete, the suture on stent can be performed.

PMID- 12053447
TI  - [Retrospective study on the incidence and cause of drop-out during intracavernous
      pharmaco-prosthesis therapy].
AB  - OBJECTIVE: We report a retrospective analysis of 394 patients affected by
      erectile dysfunction and enrolled in a self-injection program after a positive
      injection test with alprostadil or vasoactive mixture, evaluating the rate and
      the causes of drop-out. We analyzed these data in two different groups of
      patients, classified on the basis of the training received before home therapy.
      METHODS: 286 patients, included in group I, were trained in a single visit, in
      which the technique of injection was demonstrated on a rubber model. 108
      patients, included in group II, were trained in a first office visit, consisting
      in demonstration and guided self-injection, and a home training trial of 3 self
      injections, each followed by an office visit in which any questions or problems
      encountered during home therapy were discussed with the physician. All the
      patients enrolled in the self-injection program were contacted, after a follow-up
      of 2-8 years, and invited to an office visit or a phone interview, in order to
      answer to a questionnaire. RESULTS: 62% of the patients of group I had
      discontinued therapy. Among these inactive patients, 79% had ceased therapy
      during the initial four self-injections. The most commonly cited reason for
      attrition was ineffectiveness (61%), followed by recovery of spontaneous erectile
      activity (17%). Satisfaction rate with therapy in active patients was high, with
      89% of patients reporting a score of 3 (satisfied) or 4 (very satisfied). Among
      the 99 patients of group II, only 4 had discontinued therapy. Two of them had
      dropped out because of a recovery of potency. A high rate of patients satisfied
      with therapy was observed also in this group (78%). CONCLUSIONS: Data provided by
      the patients enrolled in a self-injection protocol confirm alprostadil as a very
      effective and well tolerated therapeutic option for erectile dysfunction. The
      high drop-out rate registered during the initial period of therapy, and
      ineffectiveness as the most cited reason, underline the importance of a closer
      monitoring of patients in the early therapy in order to improve acceptance.

PMID- 12053448
TI  - [Ureteral endometriosis: urological features].
AB  - Endometriosis affects about 10-20% of premenopausal women but ureteral
      involvement is an infrequent event occurring only in 0.1-0.4% of cases. Clinical
      presentation and radiological aspects are non-specific so that preoperative
      diagnosis is difficult, requiring a high index of suspicion. Intravenous
      urography is mandatory in all patients with pelvic endometriosis. Between 1995
      and 2001, 10 patients with severe endometriosis of the ureter were referred to
      our center. Bilateral involvement was present in 3 cases. 6 patients showed a
      significant involvement of other pelvic organs, with subsequent surgical
      treatment. 1 patient with bilateral ureteral endometriosis was treated by
      bilateral stenting and medical hormonal therapy, with good results. 2 patients
      underwent ureteral resection with primary reanastomosis; one of them showed an
      ureteral relapse 22 months after surgery, with the necessity of a second
      resection and ureteroneocystostomy. Ureteric resection and ureteroneocystostomy
      were initially performed in the other 7 patients, without evidence of recurrences
      in all cases (median follow-up 31 months). Hormonal therapy or
      hysteroadnexiectomy, when feasible, are necessary to reduce the risks of
      relapses. In our opinion, ureteral resection associated with ureteroneocystostomy
      gives the best chances to cure severe ureteral endometriosis.

PMID- 12053449
TI  - [Use of levofloxacin in the antibiotic prophylaxis for diagnostic procedures in
      urology].
AB  - Chemoprophylaxis is the use of antimicrobial agents before contamination in the
      hope of preventing infections. The need for prophylaxis depends on the type of
      procedure and the risk for each individual patient. The risk for infection from
      urethral catheterization in a hospital setting is 5% for men and 10-20% for
      women, after routine cystoscopy is 4.7%, after transurethral resection of the
      bladder (TURB) is 39%, after transurethral resection of the prostate (TURP) is 6
      43%, after transrectal biopsy of the prostate is 6.2-87%, and after shock wave
      lithotripsy is 5.7%. On this basis prophylactic treatment is recommended in all
      patients for transrectal prostate biopsy and transurethral surgery and in
      patients with increased risk of infection for diagnostic endoscopy of the urinary
      tract and SWL. Risk factors such as age, immunosuppression, metabolic dysfunction
      (e.g., diabetes), reduced general condition, prolonged operative time and
      bleeding, should be considered. Broad-spectrum cephalosporin, penicillins and
      fluoroquinolones are most often used. The choice of the drug also depends on its
      pharmacokinetic properties that should secure effective tissue levels during the
      procedure. Levofloxacin meets these criteria and reduces the incidence of
      infection after transrectal prostate biopsy and endoscopy of the urinary tract.

PMID- 12053450
TI  - [Obstructive uropathy secondary to recurrent pelvic endometriosis: description of
      a clinical case].
AB  - The typical presentation of endometriosis is pelvic pain. Patients with with
      endometriosis often have associated fertility disorders even if their
      relationship with the symptoms and signs of endometriosis is not evident. The
      first line of treatment for endometriosis must be surgery. In case of infertility
      the preferred approach is laparoscopic, maybe in association with medical
      treatment and possibly followed up by a second-look. In cases with relevant
      pelvic pain and involvement of other organs, laparotomy is necessary,
      particularly when a deep endometriosis is infiltrating the uterosacral ligaments,
      the rectovaginal septum and the bladder. Medical treatment of endometriosis is
      based upon the hormone-dependency of the endometriotic lesions inducing a resting
      status. Adhesions, endometriomas or fibrous sequelae do not respond to medical
      treatment. We describe a case of recurrent endometriosis treated with radical
      surgery for relevant lesions and fibrous adhesions of ureters with consequent
      bilateral hydronephrosis.

PMID- 12053452
TI  - [Metastatic penile lesions secondary to transitional cell carcinoma of the
      bladder: a rare cause of "malignant priapism"].
AB  - Metastases to the penis from transitional cell carcinoma of the bladder are rare.
      In the literature about 300 cases of secondary penile malignancies were
      described; 35% out of these cases were from primary neoplasms of the bladder. The
      Authors describe a case of priapism secondary to penile metastases from a
      transitional cell carcinoma of the bladder.

PMID- 12053451
TI  - Primary lymphoma of the kidney. Report of a case and update of the literature.
AB  - OBJECTIVES: To report on a case of primary renal lymphoma (PRL) and update the
      literature concerning this topic. MATERIALS AND METHODS: A 48-year-old woman
      underwent surgery for the presumed diagnosis of renal cell carcinoma with
      bilateral adrenal metastases. RESULTS: The neoplasm was assessed as primary renal
      non-Hodgkin high grade lymphoma, diffuse large B-cell type. Then the patient
      underwent polychemotherapy according to the VACOP-B protocol. Unfortunately, 5
      weeks later the patient was lost since missing chemotherapy and follow-up.
      CONCLUSIONS: PRL is a distinct pathological and clinical entity which is
      extremely rare and highly aggressive since disseminating rapidly from its origin.
      The disease usually affects adults with an average age of 60 years and slight
      male preponderance; however it has also been reported in childhood. Etiology
      factors for PRL are unknown. Several histogenetic theories of the disease have
      been postulated since the kidney does not normally contain lymphoid tissue.
      Investigators reported many classes of non-Hodgkin lymphoma which include large,
      small, intermediate and mixed cell types with high, intermediate or low grade
      histologies. The neoplastic lymphoid cells may express both B and T immunoblastic
      phenotypes, primary renal Hodgkin lymphoma has also been reported. The disease
      may present with progressive renal failure of either oliguric or non oliguric
      type. Imaging studies in diagnosing and staging primary renal lymphomas include
      ultrasound examination (US) and computed tomography (CT); there are also some
      reports of magnetic resonance imaging (MRI). Total body bone scan and bone marrow
      biopsy will complete disease clinical staging. Renal biopsy is important in
      assessing the diagnosis of PRL as well as of acute renal failure for bilateral
      lymphomatous infiltration of the kidneys. Up to now, there are no standard
      treatment modalities for this entity since the small number of cases reported.
      Multidrug chemotherapy is mandatory for high grade lymphoma and when the disease
      is diagnosed preoperatively. High dose chemotherapy in the future may offer a
      curative approach in primary bilateral renal disease and without end-stage renal
      disease. Survival is extremely poor since 75% of patients die less than 1 year
      after operation. Prognosis may be improved by early detection of disease and by
      performing systemic chemotherapy.

PMID- 12053453
TI  - [Post-radiation pelvic disease and ureteral stenosis: physiopathology and
      evolution in the patient treated for cervical carcinoma. Review of the literature
      and experience of the Radium Institute].
AB  - Ureteral stenosis secondary to radiation-induced fibrosis is a well-known, late
      complication of radiation treatment in patients with carcinoma of the uterine
      cervix. This paper focuses on epidemiological data, physiopathology and treatment
      modalities reviewed from Internet-published literature. Experience from a single
      institution (Institute of Radiotherapy of Brescia) is reported. Ureteral stenosis
      has an incidence of 15% in patients treated with standard doses of radiotherapy
      for carcinoma of the uterine cervix. An asymptomatic low-grade fibrotic ureteral
      stenosis establishes at doses of 20 Gy in experimental animal models, and both
      incidence and severity rise with increasing of doses. An emerging role for
      Transforming Growth Factor beta 1 (TGF-beta 1) is recognized in determining
      chronic activation of fibroblast/fibrocyte lineage and remodelling extracellular
      matrix which are known mechanisms in the genesis of any fibrotic disease.
      Experience of the radiotherapy Institute of Brescia, Italy, is reported. A series
      of 191 patients with stage IB-IIA cervix carcinoma was treated with radical
      radiotherapy. About 10% of patients developed late urinary tract complications
      related to post-actinic fibrosis with only 1% of grade III-IV ureteral fibrosis.
      These data are consistent with those published by other institutions. In
      conclusion, late ureteral fibrosis is a common and distressing treatment-related
      complication in patients treated with radiotherapy for cervix carcinoma. Newer
      strategies in better defining the target for radiotherapy, conformational
      radiotherapy and better understanding of biologic factors will contribute to
      further reducing the frequency of such a complication.

PMID- 12053454
TI  - Treatment decisions about lumbar herniated disk in a shared decision-making
      program.
AB  - BACKGROUND: An explicit process of collaborative (shared) decision making
      involving the patient and physician has been recommended for discretionary
      surgical procedures in which small-area analysis demonstrates high variation not
      attributable to differences in the patient population in the area. One such
      example is laminectomy for lumbar herniated disk (HD). An observational study was
      undertaken to evaluate the impact of an HD videodisk program on patient
      satisfaction, decision making, and treatment preferences. METHODS: Enrollment
      occurred in the outpatient offices of surgeons treating Kaiser Permanente
      (Colorado Region) patients with HD who had indications for surgery. Enrollment
      took place from May 1993 to December 1995, and follow-up surveys of patients were
      completed by January 1997. RESULTS: A 6.0% decrease in the undecided group and a
      1.3% decrease in the group preferring nonsurgical treatment drove a shift of
      patients toward laminectomy, from 26.7% to 35.8% (Wilcoxon signed rank test =
      349.5, p = .017). Postviewing preference (74.0%) was a better aggregate predictor
      of the ultimate treatment than previewing preference (70.0%) for laminectomy.
      DISCUSSION: Viewing the videodisk increased the preference for laminectomy.
      However, limitations in the data prevented us from determining whether this
      change in preference was actually reflected in patients' ultimate decisions. The
      fact that the strongest predictor of choosing surgery was the patient's valuation
      of his or her condition supports shared decision making, with its emphasis on
      patient's values. Participation in other videodisk programs has been low; perhaps
      physicians should ask patients to view these videodisks before their visits.

PMID- 12053455
TI  - Assessing performance reports to individual providers in the care of acute
      coronary syndromes.
AB  - BACKGROUND: As part of a quality improvement initiative in the management of
      acute coronary syndromes, performance reports on care of patients with acute
      myocardial infarction (MI) or unstable angina (UA) who were admitted to two
      cardiology services at the University of Michigan Medical Center in 1999 were
      disseminated to a range of providers. METHODS: In 1999, data were routinely
      collected by chart review on presentation, comorbidities, treatments, outcomes,
      and key process of care indicators for nearly 300 patients with AMI and a similar
      number of patients with acute UA. Key process of care indicators and outcomes
      were the focus of the report cards for AMI and UA. RESULTS OF SURVEY ON REPORT
      CARDS: The return rate for the provider survey--a simple one-page, nine-item
      question/answer sheet--was highest among faculty who received physician-specific
      reports (14 out of 17; 82%). Overall, 18 (60%) of 30 providers indicated that the
      report was useful, 18 responded favorably to the format, and only 3 (10%)
      indicated that the information was repetitive. Importantly, 24 (80%) indicated a
      desire to see future performance reports. DISCUSSION: Although hospitalwide or
      even statewide reports have become familiar, their overall impact on care within
      hospitals or health systems is unknown. Because so many different caregivers
      affect the care of a single patient, it is difficult to identify all of these and
      to consider which part of the care oversight should be ascribed to each provider.
      The care process itself must be reengineered to build in the systems and time
      required to accomplish continuous evaluation and improvement.

PMID- 12053456
TI  - Collaboration is in the eye of the beholder.

PMID- 12053457
TI  - The new paradigm of crew resource management: just what is needed to re-engage
      the stalled collaborative movement?
AB  - The literature is replete with examples of collaborative studies and research
      from 1960 to about 1995, after which the movement seems to have lost momentum.
      With the emergence and focus on patient safety issues, the importance of
      collaboration and a team approach to patient care has become paramount. CRM is a
      communication methodology developed by the aviation industry, based on team
      centered decision making systems. Once we have identified the key components of a
      successful collaborative model, it is imperative that we incorporate them into
      the health care providers' educational curriculum, both in training as well as in
      the practice setting. Effective communication must be identified as a necessary
      skill, and collaboration as a conscious, learned behavior. The dream of
      collaboration has been deferred long enough, and CRM shows promise for re
      igniting the collaborative movement.

PMID- 12053458
TI  - Working together but apart: barriers and routes to nurse--physician
      collaboration.
AB  - The authors argue that the aircraft safety model may be of limited relevance for
      health care and suggest strategies for greater collaboration between nurses and
      physicians in the care of patients.

PMID- 12053459
TI  - Using health care Failure Mode and Effect Analysis: the VA National Center for
      Patient Safety's prospective risk analysis system.
AB  - The authors describe HFMEA, a five-step process used to proactively evaluate a
      health care process, and provide examples of a team's forms and actions regarding
      prostate-specific antigen testing.

PMID- 12053460
TI  - Pursuing perfection: an interview with Don Berwick and Michael Rothman. Interview
      by Andrea Kabcenell and Jane Roessner.
AB  - Don Berwick and Michael Rothman discuss the Pursuing Perfection initiative, which
      is intended to help health care organizations integrate improvement work into day
      to-day life, with systemwide changes in infrastructure, project management, care,
      and leadership.

PMID- 12053461
TI  - [Eppur si muove!].

PMID- 12053462
TI  - Effects of nerve and fibroblast growth factors on the production of nitric oxide
      in experimental model of Huntington's disease.
AB  - The role of nitric oxide (NO) in neurological diseases represents one of the most
      studied, yet controversial subjects in physiology. The aim was to examine the
      effects of intrastriatal injection neurotrophins (nerve growth factors-NGF,
      fibroblast growth factors-FGF) in order to investigate the possible involvement
      of NO in quinolinic acid (QA) induced striatal toxicity in the rat model of
      Huntington's disease (HD). QA was administered unilaterally into the striatum of
      adult Wistar rats in a single dose of 150 nM. The other two groups of animals
      were pretreated immediately before QA application with NGF and FGF, respectively.
      Control group was treated with 0.9% saline solution in the same manner. Animals
      were decapitated 7 days after the treatment. Nitrite levels were significantly
      decreased both in the ipsi- and contralateral striatum and forebrain cortex of
      NGF- and FGF-treated animals compared with QA treatment. These results indicated
      a temporal and spatial propagation of oxidative stress and spread protective
      effects of NGF and FGF on the forebrain cortex, the distant structure, but
      tightly connected with striatum, the place of direct neurotoxic damage.
      Neurotrophins could be the potential neuroprotective agents in HD.

PMID- 12053463
TI  - [Intraoperative rupture of cerebral aneurysms and use of temporary arterial
      occlusion].
AB  - OBJECTIVES: The aim was to analyze the risk factors for intraoperative rupture
      (IR) of cerebral aneurysm and for temporary clips (TC) use, as well as their
      influence on the final postoperative outcome. METHODS: Retrospective study was
      done 72 IR patients, and on 75 TC patients. For patients with or without IR, as
      well as for the patients with or without TK, outcome of the treatment, aneurysm
      size and localization, preoperative clinical state and operative timing was
      analyzed, and statistical significance of obtained differences was tested.
      RESULTS: IR occurred in 40% of anterior cerebral artery aneurysms and in 16.7% of
      internal carotid artery aneurysms (p > 0.05), while TCs were used in 52% of
      middle cerebral artery aneurysms and 34.8% of internal carotid artery aneurysms
      (p > 0.05). Average size was 17.3 mm for aneurysms with IR and 11.7 mm for those
      without IR (p > 0.05). Aneurysms were significantly larger in patients with TCs,
      than in patients without TCs (16.7 mm and 9.4 mm respectively, p < 0.05).
      Preoperative period was 10.2 days for patients with IR, and 16.8 days for
      patients without IR (p < 0.05). Favorable outcome was observed in 71.4% of
      patients with IR and in 70.6% of those without IR, as well as in 76.4% of
      patients who required TC and in 75.6% of cases without TC (p > 0.05). Average
      duration of temporary occlusion was 5.8 min for patients with favorable outcome
      and 15 min for patients with poor outcome (p < 0.05). CONCLUSIONS: Incidence of
      IR mostly depended on the duration of preoperative interval, while the frequency
      of TC use depended mostly on aneurysm size. IR did not influence the surgical
      outcome, as well as TC use, if the occlusion was shorter than 8-10 min.

PMID- 12053464
TI  - [Correction of congenital blepharoptosis by transposition of the frontal muscle].
AB  - Congential ptosis (CP) represents a significant reconstructive problem. Numerous
      studies have not yet provided full and satisfactory results. In this study, we
      have presented our experience in the surgical treatment of 108 patients by the
      use of Son Ye Guang's modified method--frontal muscle transposition. A total of
      108 patients with CP were surgically treated at the Clinic for Plastic Surgery
      and Burns of the Military Medical Academy in the period 1991-2000. Unilateral
      ptosis was operated in 85 patients, and bilateral in 23 patients. CP was more
      frequently found in males (58.34%) than in females (41.66%). The youngest patient
      was only 5.5 years old, and the oldest was 42, the average age was 21.3 years.
      All patients were operated on by the same surgeon, and were monitored monthly
      during the first six months, and then twice a year for the next 3 years.
      Postoperative results were evaluated after 6 months: the action of raising the
      eyelids was compared to the full amplitude of movement of the eye on the healthy
      side. The closure of the eyelids and the symmetry of the palpebral fissure in a
      steady horizontal view was also assessed. The action of the opening as well as
      closure of the eyelids in full amplitude was obtained in all operated patients.
      Assymetry of the palpebral fissure in a steady horizontal view up to 1 mm did not
      require additional correction. In 9 cases, assymetry of the palpebral fissure
      greater than 1 mm was subsequently corrected. The advantages of this surgical
      method compared to the other, previously described techniques, were emphasized in
      the conclusion. The main advantage was the elimination of postoperative
      lagophthalmos, which represented the problem in all previously used methods.

PMID- 12053465
TI  - [Advanced prostatic carcinoma with low levels of serum prostate-specific
      antigen].
AB  - The serum levels of prostate-specific antigen (PSA) represent a significant
      diagnostic and monitoring parameter of prostatic carcinoma (PC). The aim of the
      study was to establish correlation of serum PSA level in addition to grade,
      histological type, and clinical stage of PC in patients with normal or
      intermediary PSA serum level. In 37 untreated PC patients with preoperative serum
      PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum
      samples were immunohistologically studied and immunoassay for PSA was done. The
      most representative was poorly differentiated PC with D stage. In serum samples
      from PC patients 27 (73.7%) normal (< or = 4.0 ng/ml), and 10 (27.3%)
      intermediate (4.1-10 ng/ml) PSA levels were found. Immunohistochemistry, in 36 PC
      (97.3%) had demonstrated the expression of PSA. Our study results had shown low
      serum PSA levels in some patients with advanced poorly differentiated PC.

PMID- 12053467
TI  - [Can the use of computer tomography and transesophageal echosonography decrease
      the number of exploratory thoracotomies in pulmonary carcinoma?].
AB  - A group of 49 patients (41 males, 8 females) with locally confined non small cell
      lung carcinoma, of the average age 58.48 +/- 9.05 years, was retrospectively
      analyzed. Bronchoscopy, computed tomography of the thorax and transesophageal
      echosonography were performed in all the patients to evaluate preoperatively the
      locoregional dissemination of the disease as well as the tumor resectability. The
      aim was to establish whether the complementary use of computed tomography and
      transesophageal echosonography could decrease the number of explorative
      thoracotomies. Resectability evaluation by computed tomography, burdened by many
      falsely negative results, could lead to 15 (30.61%) explorative thoracotomies.
      When transesophageal echosonography was performed, only 3 (6.12%) falsely
      negative results were obtained. Resectability evaluation by complementary use of
      computed tomography and transesophageal echosonography would be the best, with
      only 1 (2.04%) explorative thoracotomies necessary. By such procedure, it was
      possible to set the optimal indications for surgical treatment with the minimal
      number of explorative thoracotomies.

PMID- 12053466
TI  - [Role of various virus genotypes in progression of chronic hepatitis C].
AB  - The relation between HCV genotypes and the progression of chronic hepatitis is
      still unknown. Some studies implied more pathogenic effect of genotype 1b for the
      severity of liver inflammation. However, other studies did not show the
      association between HCV genotype 1b and the severe outcome of HCV infection. The
      aim of this study was to determine the most frequent genotypes in this
      environment and their influence on hepatitis C severity. The investigation
      included 34 patients with histologically confirmed chronic hepatitis C, aged 20
      65 (mean 35.0 years). On the basis of pathohistological findings, applying the
      modern classification, the disease activity was graded as: minimal (A1) moderate
      (A2) and severe (A3). The extent of fibrosis was marked as: absent (F0), mild
      (F1), moderate (F2) and severe (F3). Genotyping was performed by nested PCR with
      type-specific primers and LIPA test and verified by sequencing. The most
      prevailing genotype in our group of patients was 1b (44.1%), followed by genotype
      3a (26.4%), genotype 1a (11.7%) and 2a (2.8%). Five patients had mixed genotypes
      (four 3a/1b, and one 1a/1b). The severity of liver cell necrosis, measured by
      alanintransferase (ALT) levels in serum was not related to any of HCV genotypes.
      There was no statistically significant difference between histological disease
      activity in relation to HCV genotypes. Stage of the disease was not significantly
      related to the HCV genotypes. There was a strong association between the degree
      of fibrosis and the age of patients (p < 0.01). These results could indicate that
      the determination of HCV genotypes was not useful in the estimation of disease
      severity and that liver biopsy was the most important for the prognosis of the
      disease.

PMID- 12053468
TI  - [War injuries of blood vessels of the extremities].
AB  - Treatment results of 200 injured with the lesions of 282 magistral blood vessels
      were analyzed. All were combat injuries, and the majority was caused by the
      fragments of explosive device. The mechanisms of such the injuries produced large
      defects of soft tissues as well as the high level of the wound contamination,
      which aggravated reconstructive procedures and increased the risk of infection.
      In the majority of cases anatomic reconstruction of the artery was performed, and
      the ligature was used only in the case of graft infection and in the injuries of
      one artery of the lower leg or the forearm. The majority of injuries was solved
      by lateral suture or patch plastic, since postoperative constriction caused by
      those methods did not cause greater hemodynamic disorders due to the size of
      venous lumen. The duration of ischemic interval was of the utmost importance for
      the favorable final result of the treatment, as well as the adequate debridement
      of the wound, good soft-tissue cover of the reconstructed blood vessel and
      precise atraumatic technique. Total percentage of amputations was 14.5%, and all
      were involving the lower extremities, and were mostly caused by popliteal artery
      lesion.

PMID- 12053469
TI  - [An epidemic of Q fever in a unit of the Yugoslav Army during war conditions].
AB  - In an outbreak of Q-fever in an Army unit lasting 9 days, 20 (13.4%) soldiers had
      contracted a disease. The outbreak occurred due to the entry of the unit into the
      focus originated by lambing and pasture of infected sheep. The source of the
      infection was the contaminated dust from the grassland where the soldiers were
      training, and they were infected by aerogenic way. In 11 (55%) patients, the
      disease was manifested as pneumonia that was radiologically confirmed in 7 (35%)
      patients, while the rest were with the symptoms of influenza and upper airways
      infection. As soon as tetracycline was administered, health state of the patients
      was significantly improved and all were released as cured after the treatment.
      Finding of the antibodies to Coxiella burneti in 66.6% of the patients confirmed
      the etiology of the disease in this outbreak.

PMID- 12053470
TI  - [Kidney transplantation yesterday, today and tomorrow].

PMID- 12053471
TI  - [Atherosclerosis of the aortic arch--a possible etiopathogenic factor in cerebral
      ischemic disease].

PMID- 12053472
TI  - [Models of the lipid skin barrier].

PMID- 12053473
TI  - [Gastrointestinal stromal tumors].
AB  - BACKGROUND: Gastrointestinal Stromal Tumors (GISTs) are non-epithelial, non
      myogenic, non-neurogenic, and non-lymphogenic GIT neoplasms built of spindle
      and/or epithelioid cells with the expression of c-kit proteins. Histogenesis is
      still unclear, criteria of malignancies are not adopted, biological behavior is
      not known, and the diagnosis and prognosis are questionable. The aim of the paper
      was to create clearer conclusions about the diagnosis, prognosis and treatment of
      GIST, upon the analysis of numerous cases. METHODS: On the basis of multifaceted
      search of Medline, Index Medicus and cited references, published articles were
      collected, in all languages, from the first published case in 1984 until the end
      of 2000. The analysis of 98% published articles with 2088 (99%) GIST cases was
      performed. After quantitative synthesis, qualitative analysis was obtained by
      statistical data processing. RESULTS: GISTs were represented in 1-4% of
      gastrointestinal tract (GIT) tumors, and they were most frequently (42%)
      nonepithelial GIT tumors. GIST (n = 1368) were most frequently located on the
      stomach (53%) then on the small intestine (27%), rectum (4%) and on the colon,
      duodenum, esophagus, retroperitoneum, mesenterium and omentum (2-3%).
      Histopathologic, imunohistochemical, and prognostic differences were
      significantly dependent on GIST localization. GIST (n = 1040) were equally
      present in males and females, but GIST of the small intestine was more frequently
      found in females. The average age of patients was 62 years. Symptomatology of
      GIST was nonspecific and one third of patients were asymptomatic. Imuno
      histochemical investigations (n = 1492) were necessary for the correct GIST
      diagnosis, and they were positive on: vimentin in 98%, CD117 in 90%, CD34 in 65%,
      NSE in 58%, S-100 in 21%, SMA in 33% and desmin in 8% of cases. About 55% of GIST
      had malignant behavior. At the moment of operative treatment, 20% of patients had
      liver and/or peritoneal metastases. Metastatic dissemination of GIST was not
      lymphatic. Prognosis of malignant GIST was significantly poorer compared to the
      other GIT sarcomas. The most significant clinical parameters of the disease
      behavior were tumor size and mitotic activity, and significant were: tumor
      localization, hemorrhage and necrosis in the tumor, cellularity, mucosal
      invasion, and cellular and nuclear atypia. In spite of all criteria, even the
      most benign GIST could relapse with metastases. Even the incomplete resection as
      well as the resection of recurrent tumor had enabled better survival rate.
      CONCLUSIONS: According to this analysis GIST were the most frequent stromal GIT
      tumors. Correct diagnosis of GIST was based on imunohistochemical studies, and
      biological behavior upon the clinico-pathological parameters in 90% of cases.
      Complete surgical resection was the only therapeutic option. Regional
      lymphadenectomy was not necessary. Long-term follow-up of these patients was
      necessary due to the high incidence of recurrence.

PMID- 12053474
TI  - [Necrotizing fasciitis caused by group A streptococcus].
AB  - The first case of the confirmed necrotizing fasciitis caused by Group A
      Streptococcus in Yugoslavia was presented. Male patient, aged 28, in good health,
      suddenly developed symptoms and signs of severe infective syndrome and intensive
      pain in the axillary region. Parenteral antibiotic, substitutional and supportive
      therapy was conducted along with the radical surgical excision of the necrotizing
      tissue. The patient did not develop streptococcal toxic shock syndrome thanks to
      the early established diagnosis and timely applied aggressive treatment. He was
      released from the hospital as completely cured two months after the admission.

PMID- 12053475
TI  - [The Churg-Strauss syndrome].
AB  - Churg-Strauss syndrome (CSS) is medium blood vessels vasculitis with predilection
      for lungs in patients with bronchial asthma, chronic eosinophilic pneumonia and
      positive ANCA in the sera in 55-67%. This is a case report of a 60 years old
      female patient with bronchial asthma, peripherial pulmonary infiltrations, blood
      eosinophilia, xerophtalmia, tachycardia, chronic rhinosinustis, polyneuropathia
      and negative imunological tests: CIC (PEG), CRYO, ANA (IIF), RF (aglutination)
      and ANCA (IFF: pANCA and cANCA; ELISA: proteinase 3, lactoferrin,
      myeloperoxidase. elastase, cathepsin G). Eosinophilic infiltrates in the tissues
      tested by skin and salivery gland biopsies were not found. The patient had
      fulfilled five clinical diagnostic criteria and responded well to
      imunosuppressive therapy, so this case could be classified as the ANCA negative
      angiitis and granulomatosis of CSS type.

PMID- 12053476
TI  - [Military physicians--the first recipients of scholarships to study medicine
      abroad].

PMID- 12053477
TI  - [Better late than...(41st anniversary of the Institute for Scientific
      Information)].

PMID- 12053478
TI  - [Effect of diclofop on the activity of some drug-metabolizing enzymes in the
      liver of male Wistar rats].
AB  - The study was designed to determine whether diclofop, introduced to environment
      as herbicide, would exert properties of chemical inducers of rat liver
      monooxygenase system related to CYP1A and CYP2B isozymes. For this purpose, the
      effect of diclofop on 7-etoxyresorufin O-dealkylase and p-nitroanisole O
      demethylase activities specific for CYP1A as well as on CYP2B mediated 7
      pentoxyresorufin O-dealkylase activity was studied in male Wistar rats. This
      biochemical method permits to determine whether tested compound belongs to one of
      two main types of chemical inducers. Diclofop was dosed by gavage for 4 days at
      0; 5.6, 11.2 and 56 mg/kg b.w. per day. Treatment of rats with diclofop resulted
      in significant increase in relative liver weight (RLW), to 19% and 31% above the
      control, respectively. Diclofop administered at the dose of 11.2 and 56 mg/kg
      b.w. per day induced a 3-fold (p < 0.001) and a 5-fold (p < 0.001) increase in
      the metabolism of 7-pentoxyresorufin (CYP2B-mediated reaction), respectively. No
      effect level for CYP2B induction was 5.6 mg/kg b.w per day. However, diclofop
      induced only slight increase in 7-etoxyresorufin O-dealkylase and did not show
      any effect on p-nitroanisole O-demethylase activity (CYP1A-mediated reactions).
      The results revealed that diclofop not show the ability to induce CYP1A and
      moreover it was weak inducer of CYP2B isozymes in the liver of male Wistar rats.
      Diclofop was also examined for its ability to affect the activity of phenol UDP
      glucuronosyltransferase in rat liver. The results suggest that diclofop
      suppressed phenol form of UDP-glucuronosyltransferase activity. The isozyme
      activity decreased by 50% and 35% at the dose of 11.2 and 56 mg/kg b.w. per day,
      respectively. It should be noted that this form of enzyme inactivates during II
      phase of biotransformation most chemical carcinogens and other xenobiotics.

PMID- 12053479
TI  - Further studies on the anti-oxidative effect of putrescine in sodium nitrite
      treated rats.
AB  - In recent years, dietary polyamines, including putrescine, have attracted
      considerable interest because of the suggestion that their presence in human diet
      many have some anti-oxidative properties. Therefore, studies were carried out to
      elucidate the anti-oxidative effect(s) of oral putrescine supplementation in rats
      pretreated per os with either sodium nitrite or normal saline (control). Results
      suggest that putrescine is an effective anti-oxidant agent, which mitigates
      nitrite-induced lipid peroxidation in rat liver and small intestinal mucosa.

PMID- 12053480
TI  - A pilot study on the histochemical evaluation of Na/K-ATPase and succinate
      dehydrogenase in rat intestinal villi.
AB  - Poisoning of rats with sodium nitrite has been found to decrease Na/K-ATPase and
      succinate dehydrogenase activity in the small intestinal villi.

PMID- 12053481
TI  - [Evaluation of the effect of deionized water on selected components of fat,
      carbohydrate, and protein metabolism, morphology and the acid-base equilibrium in
      the rats blood].
AB  - By virtue of the carried out experimental investigations no essential effect of
      deionized water, administered orally for 90 days in a dose ad libitum, has been
      stated to act, in the blood of rats, on the determined elements of carbohydrate,
      protein metabolism, on morphology and the peripheral blood smear. The observed
      value shifts of the indices of fat metabolism and of the acid-base equilibrium
      are contained within the limits of physiological norms for that species of
      animals.

PMID- 12053482
TI  - [Some toxicological aspects of polycyclic aromatic hydrocarbons (PAHs) effects].
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental
      contaminants. They are found through environment in the air, in the soil, in
      water, in plants, and also in food. PAHs are formed during pyrolisis and the
      incomplete combustion of organic materials. PAHs can be man-made or occur
      naturally. They undergo metabolic activation after entering the mammalian cells
      to highly toxic reactive metabolite intermediates and can irreversibly damage
      cellular macromolecules (DNA, proteins, lipids). Polycyclic aromatic hydrocarbons
      represent a class of toxicological compounds which can create a variety of
      hazardous effects in vivo, including cytotoxicity, genotoxicity, immunotoxicity,
      teratogenicity and carcinogenesis described in present paper.

PMID- 12053483
TI  - [Substance migration and health quality of packaged food].
AB  - According to legislation the producer is responsible for the product. Products
      placed on the market must be safe and the relevant documentation confirming the
      conformity of the product with the accepted limits of global and specific
      migration must be available from the producer. The provisions concerning
      acceptable migration limits (global and specific), stimulants and testing methods
      are set by the relevant regulations. Distilled water, 3% acetic acid, 10% ethanol
      and olive oil are used as stimulants of foodstuffs. The choice of an appropriate
      stimulant and testing conditions depends on the type of food expected to come in
      contact with packaging. According to provisions testing should be performed in
      the conditions, which possibly closely reflect actual or expected use of the
      packaging material, taking into account storage of the product as well as
      possible thermal processing. Test methods for global migration into stimulants
      using the cell, pouch, by immerse or by article filling are recommended. The
      criteria used to choose an appropriate testing method are set in European
      Standards EN 1186. A product meets the quality criteria as set by the legislation
      if the global migration from the packaging into stimulants does not exceed value
      of 10 mg/dm2 or 60 mg/kg and if the specific migration limit (SML), set for given
      substance is not exceeded.

PMID- 12053485
TI  - [Vegetarian diets of breastfeeding women in the light of dietary
      recommendations].
AB  - The literature review concerning selected nutritional and health aspects of
      applying different vegetarian diets by breastfeeding women was presented. The
      only two types of vegetarian diets: lactoovo- and semi-vegetarian, when properly
      composed, seem to be relatively safe for mother and her child. The most
      threatening vegetarian diets for lactating women are those including exclusively
      products of plant origin (so called restricted diets: vegan or macrobiotic). The
      results of studies performed on mothers consuming these vegetarian diets showed
      deficiencies in: vitamin B12 and vitamin D (in mothers and their infants) and
      calcium (only in lactating women). The low intake of docosahexaenoic acid (DHA)
      was also characteristic in this group. Additionally the endogenous metabolism of
      DHA is inhibited due to high proportion of linoleic vs. linolenic acid intake. It
      considered that lactating women on vegetarian diet should have a greater
      nutritional knowledge in order to avoid deficiencies which would adversely affect
      mother's and her child's health.

PMID- 12053484
TI  - [Assessment of fatty acids content in margarines available on Polish market in
      the years 1996-2000].
AB  - Fatty acids content in margarines from Polish market in the years 1996-2000 was
      investigated. 56 samples of low fat, 40 normal fat and 78 stick were examined
      derived from different producers. Considerable differences in amount of
      particular groups of fatty acids were observed during investigation period i.e.
      saturated, monounsaturated, polyunsaturated and trans isomers in the same type of
      margarines. The low fat soft type of margarines showed the most desirable from
      nutritional point of view fatty acids content--such as low level of saturated
      acids as well as absence of trans isomers.

PMID- 12053486
TI  - [Frequency intake and energy value of breakfast consumed by school youth].
AB  - The aim of study was evaluation of frequency intake and energy value of breakfast
      consumed by high school youth. The group of 126 pupils aged 16-18 years was
      investigated. Frequency intake was estimated using questionnaire and energy value
      by 24 hours recall method. The irregularity in breakfast intake as well as
      changing energy value of them has been shown.

PMID- 12053487
TI  - [Assessment of learning conditions in urban and county secondary schools in the
      first year of education's system reform].
AB  - The study was conducted in spring 2000 on the representative national sample of
      266 secondary schools. Collected data included information about the organisation
      of schools, hygienic conditions of classrooms, conditions of regular travelling
      to schools, using of day-rooms, base for physical education range of
      supplementary alimentation. It was established that on the contrary to the
      reforms program (education in different sites) secondary schools were located in
      2/3 of cases in the same site with primary schools. Analysis of data from
      independent secondary schools showed that ensuring appropriate conditions for
      education was more difficult that in case of secondary schools located with
      primary school. A lot of problems were not solved with a such consequences like
      crowded schools, poor ventilation, inappropriate lighting, inconvenient
      furniture, Significantly better base of physical education and wide range of
      supplementary alimentation may be regarded as the positive aspects of created
      system. Unfortunately only a part of children took the possibility of
      supplementary alimentation. Both positive and negative aspects of education's
      conditions in urban and country secondary schools were similar with the exception
      of better technical status of buildings, more frequently taking offers of
      supplementary alimentation and more frequently organisation of breakfast at
      country schools. Urban schools had better conditions at day rooms and frequently
      owned the physical education halls. Presenting results may serve as a basis for
      planning activities to support health needs of children at urban and country
      secondary schools.

PMID- 12053488
TI  - [The cerebellum: anatomy, distribution of mediators and their receptors,
      communication with hypothalamic structures and comparison with the hypothalamic
      paraventricular nucleus under conditions of stress].
AB  - Cerebellum is a profound structure of the central nervous system. Human
      cerebellum weighs about 150 g which represents around 10% of the total weight of
      the brain. It receives main input from sensory systems but the cerebellum
      functions as a part of the motor system. The cerebellum contributes by only few
      direct connections to motoneurons (therefore it cannot initiate any motor
      activity) but it projects profusely to all major motor control regions of the
      cerebral cortex. The cerebellum acts as a controller and coordinator. It compares
      movement intention with, performance and coordinates the equilibrium, posture and
      muscle tone necessary for the smooth coordinated motor activity. The number of
      input projections which exceed considerably the output ones (40:1) speaks out of
      an enormous analytical and synthetic capacity of the cerebellum. Interneuronal
      transmission of informations and carriage of afferent and efferent signals are
      provided by wide variety of chemical messengers (amino acids, biogenic amines and
      neuropeptides) of the local origin or delivered from the precerebellar nuclei.
      Direct and reciprocal connections between the hypothalamus and cerebellum have
      anatomically been well documented but monosynaptic contacts between the
      cerebellum and the hypothalamic paraventricular nucleus have not been approved
      yet. Cerebellum can respond to stress, however, this response may not be related
      only to the primary effect of the stressor but also to its consequences.

PMID- 12053489
TI  - [Experimental in vivo models of cerebral ischemia].
AB  - This article summarizes different types of animal stroke models as well as the
      methods of detection of induced changes.

PMID- 12053490
TI  - [Diurnal rhythm of endogenous somatostatin in patients with carcinoid].
AB  - AIM OF THE STUDY: Was to investigate the differences of the circadian rhythm of
      the endogenous somatostatin in patients with carcinoid and in healthy probands.
      METHODS: The group of 30 patients (16 men/14 women) was divided onto two groups.
      The group M of 20 (12/8) pts with metastatic disease and group B of 10 pts
      without known metastases at the time of investigation. The control group A
      included by 12 healthy probands (7/5). Plasma levels of somatostatin were
      determined by radioimmunoassay. Fisher periodogram and Halberg's cosinor were
      used for statistical evaluation. RESULTS: We confirmed the 24-hour circadian
      rhythm of somatostatin in group A, B and M. Patients of the M group when compared
      with A and B groups had higher mesor and the later 24-hour acrophase (p < 0.05)
      and 12-hour acrophase (p < 0.05). Treatment with lanreotide led to the
      significant decrease of the somatostatin mesor (p < 0.05).

PMID- 12053491
TI  - [Analysis of variability of physiologic parameters using the Poincare plot].
AB  - The noninvasive assessment of spontaneous temporal physiological parameters
      variations can provide valuable information about control systems involved in
      their complex regulations. Recently, in addition to conventional measures
      describing variability in time and frequency domains, methods based on nonlinear
      dynamics are increasingly used in physiology. The graphical analysis using
      Poincare plot analysis with subsequent qualitative and quantitative analysis is
      one of them. The aim of this paper is to provide basic information about this
      method and its application in physiological research and clinical praxis.

PMID- 12053492
TI  - [beta-Amyloid, cholinergic neurons and Alzheimer's disease].
AB  - Alzheimer's disease is the most common neurodegenerative disorder in men and its
      incidence increases with the prolongation of life expectancy. The late phase of
      the disease is accompanied by a failure of cognitive and mental functions. Post
      mortem examination of the brain reveals the presence of neuritic plaques and
      neurofibrillary tangles, particularly in the cortex and hippocampus, and a
      reduction of the number of cerebrocortical neurons. Biochemical changes include
      the affliction of various neurotransmitter systems with the obligatory damage of
      the basal forebrain cholinergic system. Understanding of the pathogeny of
      Alzheimer's disease and, consequently, of ways to its therapy is still quite
      limited, in spite of enormous effort by investigators. Advanced molecular
      biological and genetical approaches indicate that the primary cause of
      Alzheimer's disease is the accumulation and toxic action of beta-amyloid peptide,
      which is formed as a less common breakdown product of the amyloid precursor
      protein. In this review we briefly outline some recent ideas concerning the
      origin and progression of the disease, with the main focus on the metabolism of
      beta-amyloid and on possible mechanisms of its deleterious influence on the
      neuronal, particularly cholinergic cells. Two basic cytotoxic effects of beta
      amyloid on neurons appear to be the disturbance of the homeostasis of
      intracellular calcium ions and the induction of oxidative stress, and they
      together bring about necrotic or apoptotic cell death. However, it has been found
      in experiments that the damage of cholinergic neurons and cholinergic
      neurotransmission can be induced by beta-amyloid at such low concentrations which
      do not yet evoke general cytotoxic effects. Weakening of cholinergic
      neurotransmission is known to result in an increase in the production of beta
      amyloid, and the damage of cholinergic neurons thus seems to initiate a vicious
      circle which speeds up the progression of the disease.

PMID- 12053493
TI  - Intravascular ultrasound-guided stenting in long lesions: an insight into
      possible mechanisms of restenosis and comparison of angiographic and
      intravascular ultrasound data from the MUSIC and RENEWAL trials.
AB  - The high restenosis rates in long stents may be related to suboptimal stent
      deployment. In an attempt to understand the potential components associated with
      restenosis in long stents, this study compares angiographic and intravascular
      ultrasound (IVUS) data from the MUSIC and RENEWAL studies where IVUS was used to
      optimize stent deployment in short (< 15 mm) and long (> 20 mm) coronary lesions,
      respectively. The RENEWAL study, a randomized trial, compared the NIR stent and
      Wallstent in long (> 20 mm) coronary lesions and used on-line visual IVUS
      criteria to optimize stent expansion. Detailed analysis of IVUS data was
      performed off line. Angiographic and IVUS data from this study was compared to
      that from the MUSIC study. Initial stent deployment was deemed optimal by the
      operator after visual angiographic and IVUS assessment in 50 of 70 lesions. In
      the remaining 20 lesions further balloon inflations were required to optimize
      stent apposition that led to an average gain in minimal in-stent luminal area
      (MISA) of 15.9% (P < 0.01). Off-line IVUS data analysis showed that the number
      reaching "MUSIC criteria" for optimal stent deployment preredilatation was 8
      (11.4%) of 70 and 14 (20%) of 70 postredilatation. The ratio of MISA/MRAprox
      (mean proximal reference area) was 0.69 in RENEWAL. At 6-month follow-up, the
      angiographic restenosis rate in RENEWAL was 36% and target lesion
      revascularization (TLR) rate was 7.8%, compared with MUSIC's 9.7% and 4.5%,
      respectively. In conclusion, angiographic assessment of stent deployment in long
      lesions is limited. On-line visual IVUS with further balloon inflations to
      improve stent apposition led to a significant gain in MISA, but the MISA/MRAprox
      ratio remained suboptimal. Therefore, suboptimal stent deployment due to
      constraint by lesion resistance may be an important mechanism underlying the high
      restenosis rates in long stents.

PMID- 12053494
TI  - Substantial reduction of platelet adhesion by heparin-coated stents.
AB  - Although optimized antiplatelet medication has improved the clinical outcome
      after coronary stenting, vessel occlusion and restenosis still remain a relevant
      clinical problem. Platelets play a key role in this process. Therefore, the
      authors compared the platelet adhesion on different stent surface modifications
      (electropolished without coating or coated with carbon, carbon and additional
      heparin, silicon carbide, or heparin alone) to investigate their role in reducing
      platelet adhesion. All stents and additional stainless steel plates were
      incubated in heparinized whole blood with radiolabeled platelets. After washing
      the stents and plates four times, radioactivity caused by the adhesion of
      radiolabeled platelets was measured. The adhesion of radiolabeled platelets,
      compared to uncoated, electropolished stents, was reduced through silicon carbide
      coating to 58.6%, by carbon coating with additional heparin to 32.9%, and heparin
      coating alone to 7.7%. Stent coating with heparin is the most effective among the
      examined coatings in reducing platelet adhesion in vitro.

PMID- 12053495
TI  - A time-to-treatment analysis in the medicine versus angiography in thrombolytic
      exclusion (MATE) trial.
AB  - Patients with acute coronary syndromes who are considered ineligible for
      thrombolytic therapy are at high risk of recurrent ischemia and death. This trial
      randomized 201 patients to triage angiography in the first 24 hours of hospital
      admission versus conventional medical care. Of the 165 patients who underwent
      angiography that was either protocol-driven or on the basis of physician
      preference, those who underwent angiography within 6 hours of symptom onset had a
      reduction in early and late adverse events. The rates of in-hospital recurrent
      ischemia were 15.4%, 15.4%, 17.5%, 32.4%, and 38.5%, respectively (P = 0.01 for
      trend), and rates of cumulative recurrent myocardial infarction or death were 0%,
      12.8%, 10.0%, 11.8%, and 7.7%, respectively (P = 0.48 for trend) for patients who
      underwent angiography at 0-6, 6-12, 12-24, 24-48, and over 48 hours, respectively
      from symptom onset. Future trials of invasive versus conservative therapy should
      focus on performing angiography within 6 hours of symptom onset.

PMID- 12053496
TI  - Role of prolonged intravenous heparin in unstable angina patients prior to
      coronary angioplasty.
AB  - BACKGROUND: The optimal timing of coronary angioplasty in unstable angina
      patients is controversial. Early reports suggested using 3-5 days of intravenous
      heparin and aspirin for plaque stabilization before angioplasty. There is no
      clearcut data in this regard from the published literature. The purpose of this
      study was to evaluate whether delaying the angioplasty in order to stabilize the
      plaque affected the outcome. METHODS: We reviewed the hospital course of patients
      who were admitted with unstable angina through the emergency room and ruled out
      for myocardial infarction, and who required angioplasty during the index
      hospitalization. To diminish the influence of coronary stenting and glycoprotein
      IIb/IIIa receptor blockade, we reviewed all patients admitted during 1994.
      RESULTS: Of the 305 patients, 166 patients received < or = 48 hours and 139
      patients received > 48 hours of intravenous heparin infusion before angioplasty.
      Both groups were well-matched. The procedural success was similar in both the
      groups (98% vs 97%, P = 0.72). The complication rate was similar in both groups,
      including abrupt closure, emergency bypass surgery, myocardial infarction and
      death. Length of hospital stay was significantly prolonged in the group with > 48
      hours of heparin infusion (4.4 +/- 3.0 vs 7.4 +/- 3.6 days; P < 0.001).
      CONCLUSION: In patients with unstable angina undergoing angioplasty, prolonged
      duration of heparin infusion influenced the procedural outcome or postprocedural
      complications, but prolonged the hospital stay. These data suggest that early
      angioplasty of unstable angina patients is safe and may be cost-effective, even
      in the absence of stenting and potent antiplatelet agents. However, prospective,
      randomized trials are needed to clarify the need for and duration of heparin
      infusion prior to angioplasty in unstable angina patients.

PMID- 12053497
TI  - The clinical significance of QTc dispersion measurement for risk of syncope in
      patients with aortic stenosis.
AB  - OBJECTIVES: (1) To evaluate the clinical usefulness of QTc dispersion
      determination in aortic stenosis and (2) to compare the effects of QTc dispersion
      on the occurrence risk of syncope in aortic stenosis. BACKGROUND: QT interval
      dispersion has long been known to be a marker of dispersion of ventricular
      repolarization and, hence, electrical instability. Additionally, it has been
      shown that these patients have a propensity to ventricular tachyarrhythmic
      syncope. METHODS: The study included 86 patients with aortic stenosis who
      underwent left-heart catheterization and coronary angiography during
      investigation of syncope, as well as 30 control subjects. The patients were
      characterized with regards to the presence or absence of a history of syncope and
      the severity of aortic stenosis (the degree of peak transvalvular gradient). In
      addition, QT dispersion measurements were corrected for heart rate according to
      Bazett's formula and both were measured. RESULTS: QTc dispersion was greater in
      patients with aortic stenosis than in the control subjects (60 +/- 13 msec vs 38
      +/- 12 msec, P < 0.001). Similarly, QTc dispersion was greater in the patients
      with a history of syncope than in the patients with no history of syncope (68 +/-
      12 msec vs 53 +/- 10 msec, P < 0.001). In addition, QTc dispersion values were
      greater in the patients with a high transvalvular gradient than in the patients
      with a low transvalvular gradient (65 +/- 12 msec vs 50 +/- 9 msec, P < 0.001).
      Multivariate logistic regression analysis showed that only an increased QTc
      dispersion had significant value for the risk of syncope in aortic stenosis.
      CONCLUSIONS: An increased QTc dispersion increases the occurrence risk for
      syncope in aortic stenosis. These results suggest that high values of QTc
      dispersion are a sensitive noninvasive marker for determining the risk for
      syncope in aortic stenosis.

PMID- 12053498
TI  - Initial experience with a low profile, high energy excimer laser catheter for
      heavily calcified coronary lesion debulking: parameters and results of first
      seven human case experiences.
AB  - BACKGROUND: Excimer laser coronary angioplasty (ELCA) has not been used in the
      setting of highly calcified, tight stenoses because the energies required to use
      existing catheters would lead to excessive heat damage and dissection. There are,
      however, cases that frequently benefit from debulking prior to percutaneous
      intervention. A new, small laser catheter capable of high energies and repetition
      was previously examined in vitro. This study describes the first in vivo use.
      PURPOSE: To determine the safety and feasibility of a new, low profile, high
      energy laser catheter for creating a pilot hole to facilitate coronary
      angioplasty and stenting in patients with heavily calcified and occluded coronary
      arteries where a balloon has either failed to pass or was predicted to perform
      poorly. These patients represent the first patients treated with this new
      catheter. METHODS: At a high volume center, seven consecutive patients with
      anatomy as summarized above were treated and studied with QCA and then followed
      for 30 days postprocedure for complications and Canadian Cardiovascular Society
      (CCS) angina class. RESULTS: The laser catheter crossed five out of seven lesions
      and partially penetrated the remaining lesions. The mean maximum luminal diameter
      (MLD) postlasing was 1.0 mm with Thrombolysis in Myocardial Infarction (TIMI) 3
      flow. It was possible to easily balloon and stent after the pilot hole creation
      in all but one patient. TIMI 3 was achieved for the final result after adjunct
      therapy in all patients. All patients except one, who died at 3 months
      postprocedure of stroke, were improved by an average of two angina classes. No
      late procedural-related complications developed. CONCLUSIONS: The new, low
      profile laser catheter is easy to use and achieved good results in cases where a
      balloon either failed to pass or was predicted to give poor results. Further
      trials are warranted for this niche technology.

PMID- 12053499
TI  - Ostial left anterior descending coronary artery stent positioning: partial
      preinflation prevents stent oscillation and facilitates accurate deployment.
AB  - Ostial intracoronary stent deployment is complicated by the influence of cardiac
      motion, which causes the stent to oscillate back and forth during the cardiac
      cycle. Accurate deployment can be facilitated by initial low pressure inflation
      of the balloon on which the stent is mounted. This stabilizes the stent within
      the stenosis, while still allowing adjustment of the exact stent location prior
      to deployment.

PMID- 12053500
TI  - Successful thrombus removal using 6Fr hydrolyser thrombectomy catheter in acute
      myocardial infarction via radial artery.
AB  - The 6Fr Hydrolyser thrombectomy catheter for acute myocardial infarction (AMI)
      successfully removed a massive thrombus in the coronary artery in three patients.
      The 6Fr Hydrolyser catheter could be advanced into the right coronary artery with
      bare-wire methods via a 6Fr sheath at the radial artery. This approach suggests
      that the device can be an alternative method for thrombolysis in selected AMI
      patients with massive thrombus in the coronary artery.

PMID- 12053501
TI  - Controversies in carotid stenting: an editorial perspective.

PMID- 12053502
TI  - Cerebral protection systems for distal emboli during carotid artery
      interventions.
AB  - Carotid angioplasty and stenting is associated with liberation of cerebral emboli
      that can cause periprocedural stroke. There are currently three classes of emboli
      protection devices (EPDs) that are undergoing feasibility studies and one
      randomized clinical trial. Preliminary data from a small series appear to be
      promising, and there appears to be attenuation of embolic signals on a cerebral
      Doppler exam with EPD use. However, rare strokes and patient intolerance due to
      imposed ischemia have been observed. The advantages and disadvantages of each EPD
      class and the issues involving clinical trials and surrogate end points in this
      area of study are discussed.

PMID- 12053503
TI  - Endovascular stent-grafts for the repair of infrarenal abdominal aortic
      aneurysms: a brief review.
AB  - In the United States nearly 1.5 million people have abdominal aortic aneurysms
      (AAAs). The natural history of AAAs is to enlarge and rupture. Rupture of an AAA
      results in an estimated 15,000 deaths per year. The major objective in the
      treatment of AAAs is to prevent aneurysm rupture and death. Endoluminal grafting
      for the treatment of aortic aneurysms is the most exciting topic in vascular
      surgery today. It is anticipated that approximately half of all aneurysms in the
      infrarenal abdominal and descending thoracic aorta will be repaired
      endovascularly in the future. Despite the enthusiasm for this technology, there
      are unanswered questions like the long-term fate of the device, management of
      endoleaks, and the ability to protect the patient from subsequent rupture. This
      article describes the two FDA approved devices in clinical use today and the
      indications, techniques, and potential pitfalls of endoluminal stent-grafting for
      the treatment of AAAs.

PMID- 12053504
TI  - Stenting of a proximal left internal mammary artery stenosis.

PMID- 12053505
TI  - [Descriptive epidemiological study of a year-long otologic consultation in a
      tertiary hospital].
AB  - Despite the spreading of Otologic care Units it is surprising the lack of
      comprehensive epidemiologic descriptions of patients attended in these
      Departments. A greater efficacy would be the result of better protocols designs
      and consequently a much better sanitary behaviour. We make a register of
      protocols and several aspects epidemiologic and diagnostical of our first
      consultations in the Unit during 1998. Were studied 595 cases, 320 women and 275
      men, middle age was 49.91 years. From each one was controlled and analyzed the
      age, the sex, where they come from under the sanitary view-point, consult reason
      and diagnosis achieved.

PMID- 12053507
TI  - [Major myocutaneous pectoralis flap for the head and neck repair].
AB  - The AA. report the outcomes of a retrospective study done with 22 patients
      operated on the mouth cavity, pharynx and larynx, all in advanced evolutive
      stages. The repair take place through a myocutaneous flap of pectoralis major
      muscle. Viability was excellent in 77.3% percent of patients, regular in 27.3%
      and disgusting in 9.1%. Swallowing normal in 54.5%, regularly in 27.3% and bad in
      18.2%. Language was normal in 45.4% of cases, intelligible in 36.4% and almost
      incomprehensible in 18.2% of members of the whole group.

PMID- 12053506
TI  - [Post-traumatic carotid cavernous fistula as a cause of objective tinnitus].
AB  - Reporting the case of a patient, seen in our Hospital Consulting Department,
      enduring heavy pulsatile tinnitus, following a craniocerebral traumatism. ENT
      examination was negative, but having the feeling of a carotid-cavernous fistula,
      angiographies confirmed this pathology. Embolisation of the fistula as treatment
      stopped the patient's symptomatology. We take the advantage of this case in order
      to review the etiology, the pathology, diagnostic measure and treatment of this
      condition.

PMID- 12053508
TI  - [Dysphagia in cervical hyperostosis of Forestier's disease].
AB  - Some rachis conditions can produce dysphagia. We report one case of extrinsic
      oesophageal dysphagia, unusual but not exceptional problem. A 76-year-old patient
      suffering on idiopathic vertebral hyperostosis or Forestier's disease. He showed
      an enormous osteophytes widespread throughout the cervical vertebrae, fusing
      together and causing the extrinsic compression both of hypopharynx and
      oesophagus. Bibliography perusal.

PMID- 12053509
TI  - [The importance of larynx electromyography for the differential diagnosis of
      vocal cord fixation].
AB  - Fourteen patients have been studied, with precedents of endotracheal intubation,
      suffering dysphonia and fixation of one vocal cord (13 cases) or both (1 case).
      The lack of neutrogen signs was confirmed through conventional electromyography,
      and objectivity because the clinical findings pointing to a direct traumatism of
      the vocal cord, the cricoarytenoid joint or an inflammatory origin of the damage.
      We support the limitation of electromyographic procedures of the larynx facing
      the conductive techniques and concede the possibility of the use of magnetic
      stimulation with this purpose.

PMID- 12053510
TI  - [The neck cysts and infectious mononucleosis due to cytomegalovirus].
AB  - Infectious mononucleosis is usually produced as primoinfection by Epstein-Barr
      virus, but the second most common cause is cytomegalovirus. Clinical presentation
      of infectious mononucleosis is a pharyngitis and tonsillitis, associated to neck
      nodes, fever and general malaise, as well as haematological features such as an
      absolute lymphomonocytosis. Occasionally it is the neck node that is more severe,
      even without initial lymphomonocytosis. We report a deep neck abscess within a
      neck node as subacute presentation of infectious mononucleosis by
      cytomegalovirus. We review the clinical presentation of infectious mononucleosis,
      specially due to cytomegalovirus, as well as the importance that this disease
      could have while dealing with diagnosis and management of neck masses.

PMID- 12053511
TI  - [Infiltrating lipomas of the face. Reporting five clinical cases].
AB  - Lipomas are benign tumors situated preferably on shallow areas of members and
      trunk, although they can be detected also on head and neck. Infiltrative lipomas
      subfasciae (intramuscular or intermuscular) are on the contrary rarities.
      Differential diagnosis with liposarcoma is important because both growths share
      the preferential those sites. Diagnosis rest upon clinical findings, biopsy with
      FNA, rounded off with TAC, MRI or ultrasounds, according to the lesion's site.
      Treatment of choice is surgical exeresis. We report 5 cases of infiltrative
      lipomas and analyze the diagnostic procedures and the treatment followed.

PMID- 12053512
TI  - [Total glossectomy without laryngectomy. Surgical techniques and its
      controversies].
AB  - Total glossectomy is the procedure for entire removal of the tongue, practice
      considered as one of the most mutilating possible done in head and neck surgery.
      Vital functions altered after tongue resection are: mastication, language and
      swallowing. It's controversial the role played by total laryngectomy considering
      the definitive split of respiratory and digestive tracts. Some AA. perform apart
      both ectomies pending of the suitable rehabilitation. OBJECTIVE: Report of a case
      of glossectomy recently operated maintaining the larynx and review the several
      operative steps, the complications until satisfactory swallow was achieved and
      perusal of literature on this controversial subject.

PMID- 12053513
TI  - [Dermoid cyst of the floor of the mouth. A case report].
AB  - This is the case of a young woman, 16-year-old, calling to our Department because
      of the appearance, in the floor of the mouth, of a mass progressively growing
      until about 5 cm diameter. Through fine needle biopsy was diagnosed of epidermoid
      cyst. Despite its size and infrahyoid site was removed successfully. Perusal
      review of last years bibliography and its variants.

PMID- 12053514
TI  - [Thrombophlebitis of the lateral sinuses. A difficult diagnostic case for nine
      otorhinolaryngologists].
AB  - Since the advent of antibiotic era lateral sinus thrombophlebitis has become an
      scarce complication in otology. The clinical picture can present under several
      aspects, specially if given a course of antibiotics previously, which complicates
      the diagnose. We report a case recently treated and compare ours with the classic
      symptomatology quoted in the literature.

PMID- 12053515
TI  - [Microsatellite analysis of the 3p13-p25 region in renal cell carcinoma in
      humans].
AB  - INTRODUCTION & OBJECTIVES: Interstitial and terminal deletions of different
      regions of the chromosome 3 have been associated with the development of human
      nonpapillary renal cell carcinomas. We performed a microsatellite analysis at the
      region 3p13-p25 to study the role of the short arm of chromosome 3 in the
      pathogenesis of Renal Cell Carcinomas. MATERIAL & METHODS: Renal tumor specimens
      and normal kidney tissue from 57 patients were obtained after radical nephrectomy
      and immediately snap-frozen. Blood samples were also obtained from each patient,
      immediately processsed and used as normal DNA. To detect allelic loss, we used 8
      microsatellite markers covering the region 3p13-p25. Genetic alterations have
      been correlated with histology, nuclear grade, pathological stage and stromal
      cell infiltration. RESULTS: A total of 41 cases (71.9%) were clear cell renal
      cell carcinomas (CCRCC), 7 (12.3%) were chromophobe renal cell carcinomas, 5
      (8.8%) were papillary renal cell carcinomas, and 4 (7%) oncocytic tumors.
      Microsatellite analysis showed loss of heterozigosity (LOH) in 73.2% of the
      CCRCCs, and in none of the remaining histologic types. Terminal deletions were
      detected in 53.3% of the nonpapillary RCCs with LOH, and the remaining
      nonpapillary RCCs showed multiple interstitial deletions (46.6%). A common region
      of deletion in 3p14.2 has been observed. Due to contamination with normal DNA,
      when stromal cell infiltration increases, less losses of heterozigosity are
      detected. We did not find a correlation between LOH at 3p and the nuclear grade,
      nor between LOH at 3p and the pathological stage. CONCLUSIONS: 1. Microsatellite
      analysis of LOH at 3p can be used for the differential diagnosis of renal tumors.
      2. The evidence of multiple interstitial deletions in a great number of
      nonpapillary RCCs suggests that more than one gene should be involved in the
      development of nonpapillary RCC, and already present in early stages of
      oncogenesis. 3. The common region of deletion 3p14.2 suggests the presence of
      unstable sequences of DNA that play an important role in the pathogenesis of
      nonpapillary RCC. 4. LOH at 3p in most nonpapillary RCCs irrespective of the
      grade and stage, proves that these molecular alterations do not mark a more
      aggressive behaviour of the tumor.

PMID- 12053516
TI  - [Benign prostatic hyperplasia: biological significance of lymphohistiocytic
      infiltration of the adenoma].
AB  - The presence of mononuclear cells infiltrating the prostate adenoma is a
      morphological observation well established in the literature. However, its
      biological meaning is a subject of controversy. It has been postulated that it
      may represent a local immunological reaction contributing to the pathogenesis of
      prostatic adenoma. Several studies have been performed to test this hypothesis,
      both in humans and animals. The purpose of this review is to update available
      information, including our own ongoing studies. Morphological research has shown
      that cells infiltrating the adenoma are lymphocyte T, lymphocyte B and
      macrophages with a high proportion of lymphocyte T. Many of the inflammatory
      markers, such as lymphoquines (IL1, IL2, IL4, IL6, IL13), are elevated in the
      adenoma tissue as are some growth factors (EGF, TGF alpha, IFN gamma, TGF beta).
      The general impression is that an inflammatory process is activated in the
      adenoma during growth and maturing. It has also been proved that this
      inflammatory process could be modified with treatment and, in our case, with the
      lipido-sterolic extract of Serenoa Repens.

PMID- 12053517
TI  - [Diagnosis and follow up with endoluminal ultrasound in the endourologic
      treatment of experimental ureteral stenosis].
AB  - OBJECTIVES: The objective of this study is to determine the utility and
      reliability of endoluminal sonography transducer in the diagnosis and follow up
      after the treatment of partial ureteral obstruction. MATERIAL AND METHODS: Ten
      healthy Large White female pigs, weighing 35-40 Kg, were induced a partial
      ureteral obstruction by laparoscopic approach. All the studied animals underwent
      the same three-phase procedure; inducement (phase 1), diagnosis (phase 2) and
      treatment of experimental strictures (phase 3), as well as, a month follow up. In
      all the stages of the study endoluminal sonography was used to diagnose the
      stricture and to assess the treatment, as well as, to measure the internal ureter
      diameter. RESULTS: The endoluminal ultrasonography was able to assess, in all the
      cases, the affectation of all the ureteral layers. All the animals develop a
      ureteral stricture after a four weeks ligature and, except in one animal, they
      progress favourably after the treatment using the balloon rupture technique of
      the stricture ureter. The means of the ureteral diameter are: phase 1 (0.46 +/-
      0.10 cm), phase 2 (0.30 +/- 0.17 cm), phase 3 (0.47 +/- 0.13 cm). CONCLUSIONS:
      The use of the IVUS in the diagnosis of ureteral strictures results safe and
      useful, as well as, its application in the election and in the assessment of the
      treatment.

PMID- 12053518
TI  - [Hydrodynamic and biochemical effects of hypothermic perfusion of isolated kidney
      according to the type of pump].
AB  - OBJECTIVE: To study on isolated kidney perfusions by means of a self-designed
      computer-controlled organ perfusion system the hydrodynamic and biochemical
      effects of two types of pumps: a self-designed vacuum powered tubular pump and a
      classical roller pump. BASIC PROCEDURES: Experimental study performed on 12 right
      mini-pig kidneys. After transperitoneal bilateral nephrectomy, organs are
      perfused with Eurocollins solution in a randomised manner with one type of pump.
      The system records continuously perfusion pressure, flow and renal resistance.
      RESULTS: Medium renal vascular resistance was significantly lower in vacuum
      powered tubular pump perfusions. LDH level in the solution showed correlation
      with perfusion flow. CONCLUSIONS: Vacuum powered tubular pump increases renal
      flow and lowers renal vascular resistance significantly in comparison to roller
      pump. LDH level in the solution is related to good-quality hydrodynamic perfusion
      parameter values.

PMID- 12053519
TI  - [Assessment of the basal membrane status as prognostic factor in renal
      carcinoma].
AB  - OBJECTIVES: To know the basal membrane (BM) integrity in renal cell carcinoma
      (RC) and its importance as prognostic factor. MATERIAL AND METHODS: 73 patients
      with RC were selected. Immunohistochemistry with monoclonal antibodies against
      basal proteins laminin and collagen IV was performed. Percentage for BM
      fragmentation in the whole tumour was considered taking 75% as cut off. RESULTS:
      Follow-up was 6.3 +/- 4.3 years and 27 patients progressed. Correlation between
      laminin and collagen IV was significative (p = 0.000). A BM fragmentation
      expressed with laminin bigger than 75% was related to tumoural symptoms (p =
      0.019), worse grade (p = 0.004) and necrosis in more than 10% of the tumour (p =
      0.000). Fragmentation observed with collagen IV was associated to tumours greater
      than 7 cm (p = 0.014). Those patients whose tumours displayed more than 75% of BM
      fragmentation, measured with collagen IV, presented worse survival (p = 0.042). A
      similar trend was observed in the case of laminin, but it did not reach statistic
      significance (p = 0.119). In the unvariated analysis grade III-IV, more than 10%
      of necrosis within the tumour, tumoural symptoms and BM fragmentation bigger than
      75% measured with collagen IV were prognostic, while only grade and necrosis did
      so in the multivariate analysis. CONCLUSIONS: Collagen IV and laminin represent
      nicely, with a similar expression pattern, the BM fragmentation in RC. Within a
      battery of immunohistochemical markers to study RC at least one of them should be
      included because their prognostic implication.

PMID- 12053520
TI  - [Clinical and analytical parameters that might indicate a second biopsy in
      patient with high PSA and previously negative biopsy].
AB  - OBJECTIVES: To determine what clinical, analytic and ultrasound parameters, are
      more effective to predict the result of a second biopsy in patient with high PSA
      and a first prostate biopsy negative. MATERIAL AND METHODS: It was carried out a
      longitudinal study in a series of 435 cases with negative prostate biopsy. In 59
      of these cases it was practiced a second biopsy due to a permanent or sudden high
      PSA levels with or without a suspicious digital rectal examination. Of the 31
      cases with a negative second biopsy, in 4 cases it was carried out a third
      biopsy. The biopsy was made in all the occasions by transrectal ultrasound guided
      sextant biopsy. It were also valued the ultrasound characteristic of the
      prostate, the prostate volume and the proportion of free PSA. RESULTS: It was
      demonstrated statistically significant differences among the patients with a
      second biopsy negative and positive regarding: the age, proportion of free PSA,
      abnormal digital rectal examination and presence of hipoechogenic areas in the
      prostate. The multivariate analysis demonstrated that the only significant
      parameters were the proportion of free PSA and the existence of an abnormal
      digital rectal examination. Based on the data of multivariate analysis, we
      settled down for the patients with normal digital rectal examination a cut-off
      point of 0.23 of proportion of free PSA as indication for the realization of a
      second biopsy, and of 0.59 for the patients with abnormal digital rectal
      examination. This protocol applied to our series would avoid the realization of a
      second biopsy in 8 patients, and a third biopsy in 1 patient, diagnosing all the
      cases of prostate cancer. CONCLUSIONS: The digital rectal examination associated
      with the proportion of free PSA constitutes a reliable parameter to indicate the
      realization of a second prostate biopsy in patient with high PSA and previous
      negative biopsy.

PMID- 12053521
TI  - [Genetic study of six chromophobic renal carcinomas].
AB  - OBJECTIVES: To determine the role of tumor suppressor genes p53 and von Hippel
      Lindau (VHL), and the specific loss of chromosomes 1, 2, 3, 6, 10, 13, 17 and 21
      in the pathogenesis of Chromophobe Renal Cell Carcinomas (CrRCC). MATERIAL &
      METHODS: Renal tumor specimens and normal kidney tissue from 6 patients affected
      of CrRCC were obtained after radical nephrectomy and immediately snap-frozen. PCR
      SSCP analysis for mutations of p53 (exons 5-8) and VHL genes was performed in all
      cases. All of the positive cases in SSCP analysis were further characterized by
      direct sequencing. Inactivation by VHL methylation were searched by Southern blot
      analysis. Microsatellite analysis using several markers covering both arms of
      chromosomes 1, 2, 6, 10, 13 and 17, as well as 3p and 21q, was performed to
      investigate specific loss of these chromosomes. RESULTS: Mutations of p53 were
      detected in 2 (33%) of the 6 CrRCCs, showing both tumors loss of heterocigosity
      (LOH) on 17p. VHL mutations and inactivation by methylation were not detected in
      any tumor. In 5 (83.3%) of the 6 CrRCCs, microsatellite analysis showed LOH at
      every informative marker on all the regions tested except 3p. Retention of
      heterozigosity on 3p was present in all cases. CONCLUSIONS: Mutations of p53 in
      CrRCCs are more frequent (33% in our series) than in clear cell renal cell
      carcinomas (< 2% in most series). Despite 65-75% of clear cell RCCs show VHL
      mutations (60%) and inactivation by methylation (5-20%), no CrRCC in our series
      showed these alterations. LOH in the specific chromosomes tested (1, 2, 6, 10,
      13, 17 and 21) confirm cytogenetic findings that characterize CrRCCs (specific
      combinations of multiple chromosomal losses). Our results, similar to those
      reported by other authors, confirm that CrRCC is not only a histologic fenotype,
      but also a distinctive genotype from other RCCs. The specific combination of
      chromosomal losses allows a quick and easy diagnostic of this kind of neoplasms
      with a simple technique of microsatellite analysis.

PMID- 12053522
TI  - [Penile carcinoma. Retrospective study in the XIII area of the community of
      Valencia].
AB  - We have analyzed a set of 27 patients diagnosed of penile cancer who have been
      treated in our Hospital during the last 17 years (since january 1984 to december
      2000). The annual incidence was set in 1.7 patients/100,000 men/year. The average
      age has been 64 years (range 42-85). Patients delayed medical consulting of their
      lesions for 15 months (2-120). Histologic analysis found an epidermoid carcinoma
      in 19 patients, and verrucous carcinoma in 8. The average follow-up has been 48
      months (range 2-120). As a conclusion we don't belive necessary prophylactic
      inguinal lymphadenectomy. Correct followup, for early detection of lymph nodes
      does not worsen survival and it avoids unnecessary operations with a high rate of
      morbidity. The prognostic factors in our patients have been the presence of lymph
      nodes and the degree of local extension. We lack of experience with radiotherapy
      and chemotherapy.

PMID- 12053523
TI  - [Non-venereal sclerosing lymphangitis of the penis. Report of two clinical
      cases].
AB  - Nonvenereal sclerosing lymphangitis of the penis is a rare condition that
      preferably affects men aged between 20 and 40 years, and it is appeared like a
      hard cord or a nodular lesion in the sulcus coronarius penis. It is believed that
      it has origin in lymph vessels of the penis. Usually it is resolved in a self
      limited way, so the initial treatment is conservative. We report two cases, and
      some etiopathogenic, diagnosis and therapeutic aspects are discussed.

PMID- 12053524
TI  - [Giant cyst of the seminal vesicle associated with ipsilateral renal agenesis].
AB  - Cyst of the seminal vesicles represent a rare but illustrative type of
      embryologic malformation whose etiology is associated with an abnormal
      development of the mesonephric or Wolffian duct. Frequently these malformations
      are associated with an abnormal development of the ipsilateral upper urinary
      tract. The initial evaluation of the majority of cases is performed with
      abdominal or transrectal ultrasound. Considering the possible need of other
      diagnostic procedures to confirm the diagnosis, ultrasonography is safe in the
      majority of cases. The treatment of these urologic malformations should be
      restricted to symptomatic cases and usually consists of vesiculectomy, with of
      without, removal of the displastic or histoplastic kidney. We present a case of a
      right mesonephric duct malformation with a giant seminal vesicle associated with
      ipsilateral kidney agenesis and severe oligozoospermia, that presented with
      sporadic episodes of hemospermia and urinary complaints.

PMID- 12053525
TI  - [Technique of bladder catheterization after transurethral prostatic resection].
AB  - The obstacle that represents the bladder neck posterior lip after a prostate
      transuretral resection is, sometimes, the cause of sugtrigonal perforations when
      a bladder catheterization is performed after the surgery. We explain an easy
      procedure that allows a safe catheterization, reducing the risk of complications
      added to those of the surgery.

PMID- 12053526
TI  - [Primary bladder osteosarcoma treated with hemicystectomy].
AB  - Primary osteosarcoma of the bladder is an extremely rare type of tumour, and less
      than 30 adequately documented cases have been registered. From a clinical and
      radiological point of view, it is impossible to distinguish from other types of
      bladder tumours, since despite the fact that calcification of the bladder wall is
      common in osteosarcoma, other bladder diseases exist which may also present
      calcification. Prior to primary bladder osteosarcoma diagnosis, it is vital to
      first rule out the existence of an skeletal origin. Differential diagnosis must
      be carried out essentially with other bone-forming tumours, such as
      carcinosarcoma and transitional cell carcinoma with bone metaplasia. Prognosis
      for bladder osteosarcoma is extremely pessimistic, as the majority of patients do
      not survive beyond 6 months, regardless of the treatment carried out. We present
      a case of bladder osteosarcoma treated by right hemi-cystectomy, which remains
      disease free after a follow-up period of one year.

PMID- 12053527
TI  - [Melanoma metastatic to the female urethra. Report of a case].
AB  - We report a case of a 77 years old woman with an previous malignant melanoma, who
      presented an urethral metastasis. The disease was treated with conservative
      therapy by local excision after pedicle ligation, and she is free of symptoms
      after one 1 year of control.

PMID- 12053528
TI  - [Multiple urinary lithiasis and nephrocalcinosis secondary to primary Sjogren
      syndrome].
AB  - A 39 year old women with a primary Sjogren syndrome (pSS) had bilateral and
      multiple nephrolithiasis and nephrocalcinosis due to distal renal tubular
      acidosis (dRTA), hypercalciuria and hypocitraturia. She had in serum positive
      antinuclear antibodies with mottled pattern 1/320, totals ENA, Anti-SSA/Ro 52,
      Anti-SSA/Ro 60 and Anti-SSB-La antibodies. Stones were removed with
      extracorporeal shock wave lithotripsy satisfactory and were composed of calcium
      phosphate and calcium oxalate. Metabolic abnormalities were resolved with
      potassium citrate and hydrochlorothiazide. At two years of follow-up, the patient
      hadn't stone recurrence and had normal 24-hour urinary levels of citrate and
      calcium.

PMID- 12053529
TI  - Assessment of cognitive load in multimedia learning using dual-task methodology.
AB  - In two pilot experiments, a new approach for the direct assessment of cognitive
      load during multimedia learning was tested that uses dual-task methodology. Using
      this approach, we obtained the same pattern of cognitive load as predicted by
      cognitive load theory when applied to multimedia learning: The audiovisual
      presentation of text-based and picture-based learning materials induced less
      cognitive load than the visual-only presentation of the same material. The
      findings confirm the utility of dual-task methodology as a promising approach for
      the assessment of cognitive load induced by complex multimedia learning systems.

PMID- 12053530
TI  - How "implicit" are implicit color effects in memory?
AB  - Processing colored pictures of objects results in a preference to choose the
      former color for a specific object in a subsequent color choice test (Wippich &
      Mecklenbrauker, 1998). We tested whether this implicit memory effect is
      independent of performances in episodic color recollection (recognition). In the
      study phase of Experiment 1, the color of line drawings was either named or its
      appropriateness was judged. We found only weak implicit memory effects for
      categorical color information. In Experiment 2, silhouettes were colored by
      subjects during the study phase. Performances in both the implicit and the
      explicit test were good. Selections of "old" colors in the implicit test, though,
      were almost completely confined to items for which the color was also remembered
      explicitly. In Experiment 3, we applied the opposition technique in order to
      check whether we could find any implicit effects regarding items for which no
      explicit color recollection was possible. This was not the case. We therefore
      draw the conclusion that implicit color preference effects are not independent of
      explicit recollection, and that they are probably based on the same episodic
      memory traces that are used in explicit tests.

PMID- 12053531
TI  - Differences and similarities in event recall and suggestibility between children
      and adults in Germany and the United States.
AB  - Children (5-6 year olds, 7-8 year olds, 9-10 year olds) and adults from Germany
      and the United States were shown a brief video of a theft. One week later,
      participants were asked to give a free narrative of an observed event (free
      recall), followed either by sets of misleading or unbiased questions, and finally
      they were given a three-choice recognition question for each queried item. German
      participants of all ages had higher levels of correct free recall than did
      American participants. American adults and 9-10 year olds gave more correct
      responses to the open-ended unbiased questions than did their German
      counterparts. Germans of all ages made more correct responses to the misleading
      questions, whereas national differences, favoring the Germans, for incorrect
      response to misleading questions were restricted to the 5-6 year olds. National
      differences were interpreted as reflecting possible differences in strategic
      abilities, exposure to formal instruction, and the degree to which children
      experience self-directed, autonomous learning opportunities.

PMID- 12053532
TI  - Acquisition and use of mental operators: effects of type of practice.
AB  - Planning interactions with the physical world requires knowledge about
      operations; in short, mental operators. Abstractness of content and
      directionality of access are two important properties to characterize the
      representational units of this kind of knowledge. Combining these properties
      allows four classes of knowledge units to be distinguished that can be found in
      the literature: (a) rules, (b) mental models or schemata, (c) instances, and (d)
      episodes or chunks. The influence of practicing alphabet-arithmetic operators in
      a prognostic, diagnostic, or retrognostic way (A + 2 = ?, A? = C, or ? + 2 = C,
      respectively) on the use of that knowledge in a subsequent test was used to
      assess the importance of these dimensions. At the beginning, the retrognostic use
      of knowledge was worse than the prognostic use, although identical operations
      were involved (A + 2 = ? vs. ? - 2 = A). This disadvantage was reduced with
      increased practice. Test performance was best if the task and the letter pairs
      were the same as in the acquisition phase. Overall, the findings support theories
      proposing multiple representational units of mental operators. The disadvantage
      for the retrognosis task was recovered in the test phase, and may be evidence for
      the importance of the order of events independent of the order of experience.

PMID- 12053533
TI  - The impact of response mode on implicit and explicit sequence learning.
AB  - Evidence regarding the influence of response mode on sequence learning in serial
      reaction time (SRT) tasks has been mixed so far. In the present study, sequence
      learning was investigated under two different response conditions: manual (button
      presses) versus verbal (pronunciation of digits). Additionally, participants were
      divided post hoc into subgroups differing in their degree of explicit knowledge
      about the sequence. Results showed an interaction between response mode and type
      of learning (implicit vs. explicit), with explicit learning functioning more
      effectively under verbal than under manual conditions, whereas implicit learning
      was unaffected by the variation of the response mode. Implications concerning
      different underlying learning mechanisms (R-R learning vs. R-S learning) are
      discussed. Specifically, we suggest that the high response-effect distinctiveness
      of the verbal responses facilitated R-R learning.

PMID- 12053534
TI  - Tests of the power PC theory of causal induction with negative contingencies.
AB  - The power PC theory of causal induction (Cheng, 1997) proposes that causal
      estimates are based on the power p of a potential cause, where p is the
      contingency between the cause and effect normalized by the base rate of the
      effect. Previous tests of this theory have concentrated on generative causes that
      have positive contingencies with their associated outcomes. Here we empirically
      test this theory in two experiments using preventive causes that have negative
      contingencies for their outcomes. Contrary to the power PC theory, the results
      show that causal judgments vary with contingency across conditions of constant
      power p. This pattern is consistent, however, with several alternative accounts
      of causal judgment.

PMID- 12053535
TI  - The elusive matching bias effect in the disjunctive selection task.
AB  - When reasoning with conditional statements (i.e., if [not] p then [not] q), for
      example when solving Wason's selection task, subjects tend to display matching
      bias: Options which match the entities named in the rule tend to be selected
      irrespective of whether this is logically appropriate. Recently, there have been
      suggestions that the underlying causes of matching bias reflect a general
      phenomenon that applies to many types of logical rule, not just conditionals. A
      study is reported in which performance is investigated for selection tasks with
      categorical or disjunctive rules. Although matching bias was clearly present for
      categorical rules, inverted matching bias was identified for disjunctive rules,
      calling into question the generality of the phenomenon and its explanations. In
      addition, performance at one task was not correlated with performance at the
      other, calling into question recent cognitive capacity accounts of selection task
      performance.

PMID- 12053536
TI  - Goal specificity and learning with a hypermedia program.
AB  - Problem solving research has found that a nonspecific goal (NSG) leads to better
      learning than a specific goal (SG). This effect can be understood in terms of
      dual-space search theories of problem solving. To apply the theory, we studied
      goal specificity effects with a hypermedia program in which participants had to
      learn about the outbreak of World War 1, either with the goal to find twenty
      dates (i.e., SG) or with the goal to explain the reasons for the war (i.e., NSG).
      As expected, compared to the SG-group, the NSG-group correctly answered more
      factual questions about the text during the task, spent more time on average per
      page, and more often looked for extra information. In a final questionnaire with
      factual and inferential questions, the NSG-group still performed better than the
      SG-group. The NSG-group may also show better transfer of what they had learnt to
      a new situation.

PMID- 12053537
TI  - [Diagnosis of neonatal mucoviscidosis: a double probability for the future].

PMID- 12053538
TI  - [Standardized oculocardiac reflex in ex-premature near full term (93 cases)].
AB  - The aim of the study was to present data investigating vagal reactivity in a
      population of premature infants reaching term, using the oculo-cardiac reflex.
      PATIENTS AND METHODS: Ninety three premature infants, free of any disease, near
      full term at the moment of testing, were prospectively investigated at a time
      close to discharge from neonatal unit. After an all-night polygraphic recording,
      a standardized oculo-cardiac reflex test was performed during quiet sleep. Data
      were classified in relation to both chronological and postconceptional ages.
      Simple liner regression analyses were performed on the selected variables.
      RESULTS: The results showed heterogeneity of the vagal response in this
      population: longest asystole (1049 ms +/- 540; 95th percentile = 1894 ms);
      maximal percentage of deviation between two successive RR intervals (88% +/- 90;
      95th percentile = 200%); and duration between the beginning of decrease in heart
      rate and return to mean heart rate (14 s +/- 10; 95th percentile = 30 s).
      CONCLUSION: Our healthy premature infants at time of discharge exhibited a wider
      range of vagal reactivity than previously reported for the full term newborns.
      Considering our findings, we recommend caution before proceeding with treatment
      of vagal bradycardia in a similar premature infant population.

PMID- 12053539
TI  - [Genotypic exploration of a hospital neonatal outbreak due to Klebsiella
      pneumoniae producing extended-spectrum-betalactamase].
AB  - BACKGROUND: The aim of the study was to explore nosocomial neonatal outbreak of
      Klebsiella pneumoniae producing extended-spectrum-betalactamase by
      macrorestriction genotyping. PATIENTS AND METHODS: Over a 25 days period, a
      hospital neonatal outbreak due to Klebsiella pneumoniae producing extended
      spectrum-betalactamase affected 14 newborn infants admitted to a university
      hospital in Sousse (Tunisia). We collected 21 strains of Klebsiella pneumoniae
      producing extended-spectrum-betalactamase. Susceptibility testing to 17
      antibiotics was determined. Macrorestriction genotyping of strains was determined
      by pulsed-field-electrophoresis. Neonatal intensive care unit survey was
      undertaken. RESULTS: A macrorestriction genotyping subdivided 21 strains into 3
      clonally groups. Only cefoxitin, colistin, imipenem, amikacin and quinolons were
      active on the whole of strains. All infected babies died. The hygiene
      insufficiency and contamination of transfusion products at the time of their
      dividing in neonatal intensive care unit were incriminated. Handholding due to
      work overcharge was the main cause of bacterial diffusion. CONCLUSION:
      Multiclonal outbreak of Klebsiella pneumoniae producing extended-spectrum
      betalactamase appeared following hygiene insufficiency related to work
      overcharge.

PMID- 12053540
TI  - [Pancreatic involvement in inflammatory bowel diseases in children].
AB  - Pancreatitis in inflammatory bowel disease (IBD) in children is anecdotal. In
      adults, symptomatic pancreatitis occurs in 2% and asymptomatic in 8 to 21%.
      PATIENTS AND METHODS: The aim of our study was to review retrospectively the
      frequency of pancreatitis in 124 pediatric patients (54.8% boys, 45.2% girls; 97
      with Crohn disease, 16 with ulcerative colitis and 11 with undetermined colitis).
      Diagnostic criterion of pancreatitis was an increase of amylasemia > or = +2 SD
      of the normal with or without evocative clinical symptoms. RESULTS: Symptomatic
      or asymptomatic pancreatitis was found in 27% (respectively 14.5 and 12.5%).
      Pancreatitis was significantly more frequent in girls as compared to boys (P =
      0.04). Symptomatic pancreatitis was moderate and non complicated, often
      recurrent. It occurred mainly during active and severe diseases (P = 0.006). The
      localizations of IBD were not discriminant. Strong relation with drug was found
      in 25% of pancreatitis mainly due to azathioprine or 5-aminosalicylic acid, and
      salazopyrin. Duodenal localisation of Crohn disease or hepatobiliary
      complications were found associated with pancreatitis in 18% and 15%
      respectively. CONCLUSION: These data suggest the high incidence of symptomatic
      and asymptomatic pancreatitis in children with IBD, the importance of its regular
      monitoring but also its multifactorial causes. Precise diagnosis of pancreatitis
      in pediatric IBD has to be done in order to avoid inappropriate drug pancreatitis
      diagnosis.

PMID- 12053541
TI  - [Evaluation of systematic pulmonary function testing for asthma in children aged
      three to five years].
AB  - Pulmonary function testing is not usually done in the preschool child, despite
      the recent data showing early deterioration in airway function in asthma.
      METHODS: We evaluated feasibility and clinical interest of flow-volume loop by
      forced expiratory maneuver and measure of airway resistance by interrupter
      technique (interrupter resistance), before and after inhalation of salbutamol, in
      75 children aged three to five years seen in the ambulatory setting for asthma.
      RESULTS: Feasibility rate (92%) and reproducibility rate (91%) of those
      techniques were good, so that 84% of the cases could be exploited (63 children of
      75). We found few significant associations between clinical parameters and flow
      volume loop. We found a significant association between elevated interrupter
      resistance at basis and night-symptoms (P = 0.03), between diminished interrupter
      resistance after salbutamol and exercise-symptoms (P = 0.03), symptoms in the
      ambulatory setting (P = 0.02) and absence of inhaled corticosteroid treatment (P
      = 0.046). Pulmonary function testing resulted in treatment modification in 14% of
      cases. CONCLUSION: Our study shows that flow-volume loop and measure of airway
      resistance by interrupter technique can be done with a good reproducibility in
      the preschool child. Interrupter resistance appears to be better correlated than
      flow-volume loop with usually evaluated clinical parameters.

PMID- 12053543
TI  - [Neonatal enterovirus myocarditis].
AB  - Enterovirus infections in neonates are difficult to diagnose. Diphasic pattern
      and possibly fatal myocarditis must be anticipated. CASE REPORT: A 14-day-old
      girl had presented a heart failure after an initial episode of gastroenteritis
      and supraventricular tachycardia. Investigation demonstrated global myocardial
      dysfunction. Diagnosis of neonatal enterovirus myocarditis was made by polymerase
      chain reaction detection of viral genome. Heart failure was controlled with
      medical treatment. CONCLUSION: Enterovirus myocarditis is typically a biphasic
      illness. Rapid diagnosis of enteroviral infection in neonatal period may be made
      by polymerase chain reaction detection of viral genome. There is anecdoctal
      evidence that immunoglobulin infusions may improve outcome.

PMID- 12053542
TI  - [Terminal and pre-terminal chronic renal insufficiency in newborns in French
      neonatal intensive care units: survey of the French pediatric nephrologic society
      of resuscitation and emergency].
AB  - OBJECTIVES: The aim of this study was to describe the intensive care unit
      neonatologists' attitudes about a neonate with terminal or pre-terminal renal
      failure. METHODS: A questionnaire was sent to all French neonatal intensive care
      units. Physicians were asked to describe their attitude about neonatal chronic
      renal failure (Would you agree with dialysis and graft for these children?).
      Physicians were also presented with two clinical observations involving neonates
      with varying degrees of renal insufficiency and a complicating comorbidity,
      including neurological abnormality or socioeconomic circumstances. RESULTS:
      Responses were obtained from 92% of the university neonatal care units. The will
      to take care of a neonate with end-stage renal failure till the renal graft,
      varied greatly from a centre to another one. Three (9%) university-teams said
      they had a strong will to bring the baby from the neonatal period to the time of
      renal graft. Eleven other centres (32%) did not have any will for accompanying
      the baby till the renal graft. Eight centres (24%) would be rather favourable to
      the idea of dialysis and graft, and 12 others (35%) would be rather unfavourable.
      CONCLUSION: The results of this study show great differences between French
      neonatologists when they are faced to newborns with end stage renal failure.
      Ethical, medical and organisational difficulties are matters of controversy. The
      epidemiological impact of the perinatal discussion could be a 20% variation of
      all the renal grafts in children.

PMID- 12053544
TI  - [Treatment of cytomegalovirus pneumonia with ganciclovir in an immunocompetent
      infant].
AB  - Cytomegalovirus infection is common in the immunodepressed child, and because of
      its severity, is usually treated with intravenous ganciclovir. It is also common
      in the immunocompetent child, but is usually asymptomatic, so that there is no
      indication for ganciclovir treatment, because of the potential toxicity of the
      drug. CASE REPORT: We report a case of symptomatic cytomegalovirus infection in a
      six-week-old infant, presenting with interstitial pneumonia associated with
      weight and height growth failure. Cytomegalovirus was found by polymerase chain
      reaction in the bronchovalveolar lavage fluid and in the blood. This child was
      successfully treated with 15 days of intravenous ganciclovir, and experienced no
      adverse effect of this treatment. The child was free of symptoms and free of
      immunodeficiency after seven months of follow-up. CONCLUSION: Immunocompetent
      patients with cytomegalovirus infection, pulmonary involvement and weight and
      height growth failure, may benefit from intravenous ganciclovir treatment.
      Further studies, with larger number of cases, are yet needed to define more
      precisely the indications of such a treatment in the immunocompetent child.

PMID- 12053545
TI  - [Neonatal lupus erythematosus and neurologic involvement: an incidental
      association?].
AB  - Neonatal lupus erythematosus is a rare disorder characterized by cutaneous
      lesions of the face and/or congenital heart block. The transplacental transfer of
      maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP antibodies is responsible for
      the development of the disease. Few cases of neonatal lupus erythematosus with
      neurological involvement were reported in the medical literature. CASE REPORT: A
      36-week GA female infant presented with neonatal lupus erythematosus comprising
      cutaneous, hematologic and hepatic disorders with a favorable outcome. However,
      cutaneous atrophy and hyperpigmentation persisted. Spastic paraparesis was
      diagnosed at the age of six months. CONCLUSION: The neurological lesions in
      neonatal lupus erythematosus could either be related to the presence of anti
      Ro/SSA antibodies of maternal origin, or of anticardiolipin antibodies.

PMID- 12053546
TI  - [Transient left myocardial dysfunction: a cause of neonatal hypoxemia].
AB  - Refractory hypoxemia in the newborn requires an accurate diagnostic investigation
      for an optimal and prompt management. CASE REPORT: After a short delivery, a post
      term newborn developed a severe hypoxemia with patchy pulmonary alveolar
      opacities and systolic right-to-left extrapulmonary shunting through the ductus
      arteriosus. Echocardiography ruled out a cardiac malformation and showed dilated
      left atrium with left-to-right shunting by the ovale foramen due to left
      ventricular dysfunction. Inotropic support associated with mechanical ventilation
      allowed a rapid improvement. CONCLUSION: A pathophysiological analysis is needed
      in case of severe neonatal hypoxemia. Doppler ultrasound is a non invasive and
      rapid method allowing the adjustment of the therapeutic strategy.

PMID- 12053547
TI  - [Urinary antimicrobial prophylaxis].
AB  - Antibiotics are usually used to prevent childhood recurrent urinary tract
      infections: cystitis or pyelonephritis. The mechanism of action of these
      antibiotics, although imperfectly known, seems to be double: the antibiotic acts
      by its bactericidal effect, but also probably for minimal concentrations by
      reducing adhesion capability of bacteria to the urothelium. The most commonly
      used molecules are cotrimoxazole, trimethoprime, pivmecillinam, cefaclor and
      nalidixic acid. However all have not been studied rigorously as for their
      prophylactic capacity, and in particular very little is known for patients
      presenting with vesico-ureteral reflux.

PMID- 12053548
TI  - [Berger's disease in childhood].
AB  - Berger's disease or IgA nephropathy (NIgA) is the most common form of
      glomerulonephritis in the world. In children macroscopic haematuria is the first
      sign in about 80% of the patients. Renal failure appears in 20% of cases after
      twenty years of follow-up. The most important prognosis indicators are a
      nephrotic syndrome at the onset, a proteinuria > 1 g/24 hours, diffuse tubulo
      interstitial lesions and extracapillary proliferation with crescents in more than
      50% of the glomeruli. The pathogenic mechanisms are just emerging and involve a
      disrupted process of the systemic tolerance to mucosal antigen with abnormal
      mucosal gamma delta T cell repertoire, abnormally glycosylated IgA1 molecules and
      a down-regulation of Fc alpha receptors on blood cells. After IgA deposition, the
      mechanisms of mesangial cell damage and activation involve vascular factors as
      endothelin/nitric oxide system, cytokines and growth factors such as interleukine
      6, platelet derived growth factor and transforming growth factor beta. There is
      no curative treatment but steroids are useful in diffuse proliferative
      extracapillary forms, when histological activity score is high with a short delay
      between diagnosis and treatment, or for moderately severe NIgA with normal renal
      function.

PMID- 12053549
TI  - [Radiologic case of the month].

PMID- 12053550
TI  - [Practical aspects of pelvic floor training in the treatment of children voiding
      disorders].
AB  - Besides the technical aspects of bio-feed-back, pelvic floor training of voiding
      disorders in children requires a careful approach in order to understand the
      nature of the voiding disorders, and then to give clear explanations to the child
      and his/her parents. Success of pelvic floor training in large part depends upon
      the good concern and understanding of its voiding disorder by the child.

PMID- 12053552
TI  - [Human milk: a perpetual (re)appreciation].
AB  - Based upon recent studies, it appears more and more evident that exclusive breast
      feeding can be said as the best functional food, the last being defined as: "a
      food that has components or ingredients bringing a specific medical or
      physiological benefit to the host, other than purely nutritional effects". In
      particular, human breast milk does favour optimal bacterial intestinal
      colonization with bifidobacteria and lactic acid bacteria in the neonates and
      contains a large number of components with antimicrobial activity.

PMID- 12053551
TI  - [Chronic hepatitis C virus infection in children].
AB  - Peripartum transmission is today the main cause of hepatitis C virus (HCV)
      infection in children. HCV infection rarely causes a clinical illness during
      childhood and adolescence, except when it is associated with additional risk
      factors such as hepatitis B or HIV infection, chemotherapy or immunodeficiency.
      Present data suggest that between 20 to 50 percent of contaminated infants will
      become spontaneously non viremic within 15 to 20 years. Studies on treatment with
      interferon-alpha are limited and show a mean recovery rate of 40%.

PMID- 12053553
TI  - [White pityriasis].

PMID- 12053554
TI  - [Predictive factors of death in a pediatric service from Dakar: diarrhea and
      brachial perimeter].

PMID- 12053555
TI  - [Obstructive rhinitis with respiratory syncytial virus infants under 3 years of
      age and at risk for bronchiolitis].

PMID- 12053556
TI  - Increase of the radiation resistance of eucaryotic cells by means of sodium
      nitrite serving as an NO donor.

PMID- 12053557
TI  - Impaired processes of working memory in the monkey model of Alzheimer's disease.

PMID- 12053558
TI  - In vivo toxicological evaluation of polyhydroxyalkanoates.

PMID- 12053559
TI  - The system of endogenous modulators involved in the control of functioning of
      peripheral autonomic nervous structures.

PMID- 12053560
TI  - On the involvement of macrophages and phosphomonoesterases in the tissue response
      to implantation of polyhydroxyalkanoates.

PMID- 12053561
TI  - Tissue morphogenesis under the conditions of implantation of polyhydroxybutyrate,
      a biodegradable polymer.

PMID- 12053562
TI  - A new type of effect of potentially hazardous substances: uncouplers of pelagial
      benthal coupling.

PMID- 12053563
TI  - Eddy covariance assessment of CO2 accumulation by mature pine forest.

PMID- 12053564
TI  - Baikal invaders have become dominant in the upper Yenisei benthofauna.

PMID- 12053565
TI  - New definitions of the concepts and terms ecosystem and biogeocenosis.

PMID- 12053566
TI  - Frequencies of single-nucleotide polymorphisms and mutations in the BRCA1 gene in
      patients with hereditary breast or ovarian cancer.

PMID- 12053567
TI  - System of principles for conservation of the biogeocenotic function and the
      biodiversity of filter-feeders.

PMID- 12053568
TI  - Viability of higher plant seeds of late pleistocene age from permafrost deposits
      as determined by in vitro culturing.

PMID- 12053569
TI  - Feeding response of perch (Perca fluviatilis) and roach (Rutilus rutilus) fry to
      the presence of a predator.

PMID- 12053570
TI  - Snow cover as a factor of winter ecology of small mammals in the steppe zone.

PMID- 12053571
TI  - The mechanisms of endogenous control of hepatocyte proliferation are different in
      mice of two inbred strains (BALB/c and AKR).

PMID- 12053572
TI  - Specific L-929 cell death caused by cytotoxic proteins of lymphoid and erythroid
      cells.

PMID- 12053573
TI  - Mouse chromocenters contain associated telomeric DNA and telomerase activity.

PMID- 12053574
TI  - Ricin and viscumin bind to different sites of the cell membrane.

PMID- 12053575
TI  - Methane generation in permafrost sediments.

PMID- 12053576
TI  - Characteristics of the effects of neurotransmitters on the uterine contractile
      activity of immature mice of different ages.

PMID- 12053577
TI  - Behavioral and brain activity changes in users of optical filters with fractal
      matrix topology.

PMID- 12053578
TI  - Microarray technology in studying the effect of melatonin on gene expression in
      the mouse heart.

PMID- 12053579
TI  - The stimulatory effect of small doses of inhibitors in organotypic culture of
      nervous and lymphoid tissues.

PMID- 12053581
TI  - [Contemporary control of biological warfare].
AB  - Biological pathogens actually are in the focus of interest as a potential
      biological weapon in bioterrorist's disposition. In the study the main pathogens
      and their activity spectrum have been presented. The special attention has been
      paid upon aerosol way of transmission and its consequences. The possibilities of
      prevention and treatment of diseases caused by biological pathogens have been
      also discussed.

PMID- 12053580
TI  - Limbic epileptogenesis: a model study using kindling from the amygloid cortical
      nucleus.

PMID- 12053582
TI  - [Indirect evaluation of respiratory muscle strength with the help of markers of
      maximal inspiratory and expiratory pressure in the mouth of healthy individuals].
AB  - The aim of the study was the evaluation of respiratory muscle strength by
      measurement of maximal inspiratory (PImax) and expiratory (PEmax) pressures
      values. Results for 166 clinically normal subjects (79 female and 87 male) were
      obtained. The results were as follow: in woman PImax ranged 38-104 cm H2O,
      average 60 cm H2O, PEmax ranged 46-140 cm H2O average 87.5 cm H2O, in men PImax
      was 40-120 cm H2O, average 73.2 cm H2O, PEmax ranged 46-140 cm H2O, average 115.9
      cm H2O. PImax was negatively correlated with age in both groups. There was no
      correlation between age and PImax or PEmax in both groups (p > 0.05). There was
      no correlation between PImax and PEmax and height in women group and men group
      treated apart. The correlation was found between PImax as well as PEmax and
      height for whole group (p = 0.00019). There were observed positive correlation
      between PImax, PEmax and weight in both (male and female) groups. The comparison
      of results of present study with those obtained in former studies reveals
      important differences of norms for different populations. The normal values of
      maximal inspiratory and expiratory pressures in the mouth (PImax, PEmax) should
      be qualified individually for studied population. The normal values recommended
      by producers of medical equipment might be inadequate for studied population.

PMID- 12053584
TI  - [The effect of inactivation of co-stimulated particles B7.1 (CD80), B7.2 (CD86)
      on T lymphocyte activity].
AB  - We have studied the effect of CD80 (B7.1) and CD86 (B7.2) costimulatory molecules
      inactivation on IL-4 and IFN-gamma production by T lymphocytes. T cells were
      received from nonatopic asthmatic and healthy subjects. We have added anti-CD80
      or anti-CD86 monoclonal antibodies to the monocyte/lymphocyte (1:5) cultures. In
      nonatopic asthma patients compare to control group inactivation of CD80
      significantly reduced IFN-gamma production by T lymphocytes (2172/2368 pg/ml; p <
      0.02). Blockade of CD86 decreased IFN-gamma production non-significantly
      (2858/3317 pg/ml; p < 0.3). In both studied groups anti-CD80 antibodies did not
      diminish T lymphocyte production of IL-4 (control: 630/725 pg/ml; nonatopic
      asthma: 718/742 pg/ml). Anti-CD86 antibodies reduced the IL-4 concentration in
      culture supernatants (630/523 pg/ml; 718/659 pg/ml), but the changes were
      nonsignificant.

PMID- 12053583
TI  - [The role of monocytes stimulated with LPS on CD69 expression in T lymphocytes of
      patients with non-atopic asthma].
AB  - CD69 molecule is the earliest antigen of T lymphocytes activation. We have
      studied the ex-pression of CD69 on LPS-stimulated T cells in nonatopic bronchial
      asthma. We have found that CD69 expression on freshly isolated peripheral blood T
      cells in nonatopic asthma patients was increased compare to control group (4.74
      +/- 1.55/3.05 +/- 1.31) and the difference was statistically significant (p <
      0.01). Monocytes added to nonstimulated T cell cultures increased 3-4 times the
      expression of CD69 and about 10-times in LPS-stimulated T lymphocytes.

PMID- 12053585
TI  - [Precision and economy of skin prick tests].
AB  - Due to a rise in the number of cases of allergic disease and a need to increase
      financial resources for the diagnosis of these conditions, the possibility of
      reducing costs of skin pricks tests (SPT) was very welcome. In an attempt to
      reduce costs some practitioners use one lancet for several pricks in one patient.
      The purpose of this study was to determine whether this way of performing SPT
      influences the results. 52 subjects with (39) and without (13) atopy were tested
      with histamine, codeine and standard allergen extracts. SPT were applied to the
      volar surface of a randomly assigned forearm using two methods: one lancet-one
      prick on one forearm (single test method) and one lancet-multiple pricks
      ("multiple test" method) on the other. The false positive tests at the placebo
      site following allergen were recorded only in multiple test method, in 41 out of
      72 pricks (p < 0.00001) when all reactions above baseline were considered and in
      26 out of 72 (p = 0.00001) when a 3 mm cut-off was considered. The size of the
      false positive reaction depends on the intensity of the reaction to the preceding
      allergen (rang Spearman factor R = 0.706, p < 0.000001) and decreases in the
      second consecutive placebo test. Our data show that one lancet for multiple test
      method cannot be used to diagnose factors responsible for allergy, particularly
      in patients qualified for immunotherapy and in scientific studies. For financial
      reasons multiple test method can be used in screening and epidemiological studies
      where atopy is studied and there is no need to identify the specific allergen.

PMID- 12053586
TI  - [Value of the leukotriene generation test in diagnosis of immediate
      hypersensitivity to penicillin].
AB  - In this study we have decided to explore the diagnostic usefulness of CAST-ELISA
      test in patients with immediate allergic reactions caused by penicillin.
      Peripheral blood leukocytes were stimulated by commercially available penicillin
      allergens--Penicillin G, Benzyl-penicillin--Polylysine and specially performed
      Penicillin G conjugated to human serum albumin. Test was performed in 33 allergic
      persons and in 13 control healthy persons well tolerated penicillin antibiotics
      with negative skin tests results. CAST-ELISA test gave the positive results in
      30.3% when unconjugated penicillin was used and in 18.18% with penicillin-
      polylysine. The best results were obtained when cells were stimulated with
      penicillin conjugated to human serum albumin--positive results were observed in
      47.82%. Accumulate percentage of positive results was 73.91%. In our opinion CAST
      ELISA test is reliable method in diagnosis of immediate allergic reactions caused
      by penicillin and inclusion of penicillin conjugated to human serum albumin seems
      to be justifiable.

PMID- 12053587
TI  - [Aerodynamic activity of the larynx of vocal cord edema and atrophy in patients
      with presbyphonia].
AB  - The senile patients with laryngeal diseases were subjected to phonatory and
      respiratory function studies. Each patient was examined laryngologically and
      phoniatrically. The patients were divided into two groups, according to the
      changes observed in the larynx: as edema and atrophy of the vocal folds. These
      studies included phonation time (MPT), mean flow rate (MFR), phonation volume
      (PV), phonatio quotient (PQ), vocal velocity index (VVI) and spirometric
      investigations. Five physiologic criteria are recommended to establish on
      objective evaluation of laryngeal function under clinical condition (MPT, MFR,
      PV, PQ, VVI). The studies confirm the clinical importance of objective and
      quantitative measures of laryngeal function.

PMID- 12053588
TI  - [Evaluation of the voice in the elderly].
AB  - The voice analysis of 80 patients (near age 64) is presented in the study.
      Laryngeal pathology observed in the patients was classified as edema or vocal
      fold atrophy. The voice was examined subjectively and objectively (spectrographic
      examination). Voice quality pathology, voice monotony, and ill intelligibility
      were observed. The histological structure of vocal fold mucous membrane (squamous
      epithelium) was presented. Morphological changes of vocal folds are the
      underlying cause of voice pathology.

PMID- 12053589
TI  - [Usefulness of neuron specific enolase in patients with head and neck malignant
      tumors].
AB  - The authors present results of evaluation of neuron specific enolase (NSE) in 146
      persons. We analyzed a concentration of NSE in preliminary study and in
      monitoring depending on clinical advances of tumour, mass of primary tumour and
      metastases to lymph nodes. Neuron specific enolase was excluded because the
      number of positive results was the same both in the main and control group. Our
      results indicate that evaluation of NSE have not height value in monitoring
      patients with head and neck carcinoma.

PMID- 12053590
TI  - [Effect of triamcinolone acetonide, montelukast, nedocromil sodium and formoterol
      on eosinophil blood counts, ECP serum levels and clinical progression of asthma
      in children].
AB  - Eosinophil-mediated damage to the respiratory epithelium is a major pathogenetic
      mechanism in asthma. Glucocorticoids have confirmed antiinflammatory properties
      and effect of formoterol, montelukast and nedocromil on markers of inflammation
      has been studied. Eosinophil blood counts and eosinophil cation protein (ECP)
      serum level are often use as markers of clinical monitoring of the disease
      activity. To evaluate the effect of treatment on allergic inflammation, we
      measured eosinophil blood counts and ECP serum level, and clinical parameters
      before and after 4 weeks treatment with triamcinolon, montelukast, nedocromil,
      formoterol. It was 8 week, placebo-controlled and randomized, double blind trial
      of 154 children with moderate atopic asthma. Patients were randomly allocated to
      receive 400 mg triamcinolon (n = 28), 5 or 10 mg (according to age) montelukast
      (n = 27), 16 mg nedocromil (n = 26), 24 micrograms formoterol (n = 28) or placebo
      (n = 45). 140 children completed the study. After treatment with triamcinolon and
      montelukast eosinophil blood counts significantly decreased, after treatment with
      triamcinolon, montelukast and nedocromil ECP serum level significantly decreased;
      all clinical parameters improved after treatment with each drug; treatment with
      triamcinolon had the strongest effect on most parameters (except of FEV1). Mean
      eosinophil blood counts before and after treatment with triamcinolon were 277.4
      and 187.2 cells/mm3 respectively (p < 0.001); with montelukast were 279.6 and
      250.7 cells/mm3 respectively (p = 0.002); with nedocromil were 181.7 and 170.1
      cells/mm3 respectively (p < 0.183); with formoterol were 276.4 and 264.1
      cells/mm3 respectively (p = 0.2). Mean ECP serum levels before and after
      treatment with triamcinolon were 94.3 and 63.5 micrograms/l respectively (p <
      0.001); with montelukast were 85.1 micrograms/l and 71.2 micrograms/l
      respectively (p < 0.001); with nedocromil were 92.6 and 80.1 micrograms/l
      respectively (p < 0.001); with formoterol were 95.9 micrograms/l and 87.8
      micrograms/l (p = 0.05). We found significant correlation between ECP and
      hyperresponsiveness after treatment with triamcinolon, montelukast. This study
      shows that triamcinolon, montelukast contribute to inhibition of allergic
      inflammation by decreasing eosinophil blood counts and ECP. The serum level of
      ECP seems to be a good clinical marker of monitoring the disease.

PMID- 12053591
TI  - [The effect of nedocromil sodium on levels of IL-4 and IgE in serum of children
      with bronchial asthma].
AB  - Levels of pro-allergic cytokine IL-4 are increased in asthmatic airways,
      contributing to allergic inflammation. IL-4 and IL-13 are the most important
      factors in production of class E immunoglobulin, playing major role in childhood
      atopic asthma. The mechanism of effect of nedocromil, often prescribed in
      children, has been discussed. Our previous study on the effect of nedocromil on
      different inflammatory markers, showed decreased levels of IL-4 and IgE after
      monotherapy in 15 asthmatic children. The purpose of this study was to define the
      effect of treatment with nedocromil on serum level of IL-4 and IgE, clinical
      symptoms and bronchial hyperreactivity (BHR) in children with moderate atopic
      asthma. It was 8 week, placebo-controlled and randomized, double blind trial of
      81 children with moderate atopic asthma allergic to dust mite. Patients were
      randomly allocated to receive nedocromil sodium two puffs four times daily (0.002
      g/puff) (n = 34) or placebo (n = 47). 69 children completed the study. After
      treatment with nedocromil the levels of IL-4 and IgE in blood serum in study
      group significantly decreased, and all clinical parameters improved. Mean levels
      of IL-4 in serum before and after treatment with nedocromil were 0.13 pg/ml +/-
      0.01 and 0.12 pg/ml +/- 0.02 respectively (p < 0.01). Mean serum levels of IgE
      before and after treatment with nedocromil were 556.83 IU/ml +/- 201.3 and 485
      IU/ml +/- 200.5 respectively (p < 0.02). This study demonstrate that one possible
      way by which nedocromil contribute to inhibition of allergic inflammation is by
      decreasing IL-4 and IgE levels.

PMID- 12053592
TI  - [The effect of inhaled low molecular weight heparin on cell composition in
      bronchoalveolar lavage fluid and serum levels of soluble receptor IL-2 in
      bronchial asthma patients].
AB  - The 17 asthmatics were studied. The patients were administered LMWH inhalations
      during two weeks in a day dose 5000 IU anti-Xa. The cell composition in BALF and
      serum levels of sIL-2R were estimated before and two weeks after treatment. We
      found that LMWH changed significantly cell BALF profile, decreased the number of
      inflammatory cells (p < 0.005) but did not change serum sIL-2R concentrations (p
      < 0.13). Baseline serum levels of sIL-2R were normal (73.9 +/- 26.6 U/ml)
      according to producer's norm.

PMID- 12053593
TI  - [The effect of anthocyanins from Aronii melanocarpa and acetylcysteine on
      selected after-effects of lead acetate poisoning].
AB  - In recent years we have widely examined the results of protracted exposures on
      lead. Lead mostly shows that it accumulates in bones in an insoluble phosphate
      form. In much of the experimental research we observed that lead can cause
      reactive forms of oxygen and oxidative stress. The examination was carried out on
      40 female and male Wistar rats weighing 200-250 g. They lived in the animal
      quarters with a stable temperature and humidity. They were fed with standard
      fodder (Murigan) and water ad libitum. In the work carried out the effect of
      anthocyanins of Aronia Melanocarpa Elliot and acetylcysteine on the selected
      parameters of oxidative stress of experimental animals with chronic lead acetate
      poisoning were examined. After administration anthocyanins substantially
      decreased the concentration of unsaturated fatty acid peroxidation and carbonyls
      in blood serum. At the same time we observed a significant decrease of 8-hydroxy
      2'-deoxyguanosine in urine. Antocyanins from Aronia Melanocarpa appear to be a
      good substance for the diminishing of oxidative stress, these results caused with
      long-term administration of lead acetate.

PMID- 12053594
TI  - [Zafirlukast in treatment of nasal polyps in patients with aspirin intolerant
      bronchial asthma--preliminary report].
AB  - Aspirin intolerance is characterized by polypous rhinosinusitis, bronchial asthma
      and adverse reactions to aspirin. The common intolerance to all cyclo-oxygenase
      inhibitors allows us to focus study of the pathogenesis of AI on the metabolism
      of arachidonic acid. Nasal polyposis is a chronic inflammatory condition that is
      mostly characterized by an infiltration of eosinophils. How this eosinophilic
      inflammation leads to polyp formation remains largely unclear. Eosinophils are
      the major source of cysteinyl leukotrienes--potent pro-inflammatory mediators
      they can by responsible for nasal blockade, rhinorrhoea and hyperresponsiveness.
      A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of
      nasal polyps has been recently suggested and leukotriene levels have been shown
      to be elevated in patients with asthma as well as in those with sinonasal
      polyposis and sinusitis. Because leukotriene receptor antagonists inhibit
      activity of endogenous leukotrienes and decrease tissue eosinophilia it is
      speculated that these drugs may be useful also in the management of nasal polyps.
      Our study was designed to determine the efficacy of zafirlukast, a cysteinyl
      leukotriene receptor antagonist, in nasal polyposis. We conclude that
      antileukotrienes might play a role in controlling polyposis and their symptoms,
      and they might be a alternative to long-term steroid therapy and repeated
      surgical therapy.

PMID- 12053595
TI  - [Tests for the usefulness of glucocorticosteroids in treatment of experimental
      peritonitis].
AB  - In this experimental study the influence of glycocorticosteroids on the course of
      infection and prognosis in 75 rats with diffuse peritonitis was examined. We
      focused on the relation between doses, moment of pharmacotherapy introduction and
      the course of disease. To achieve this we estimated the dexamethasone doses and
      moment of its introduction on C-reactive protein (CRP), TNF-alpha and its soluble
      type I--p55 and type II--p75 receptors' concentrations in examined animals'
      serum. A diffuse peritonitis was elicited in study animals by means of cecum
      ligation and perforation (CLP). Cytokine concentrations were estimated with ELISA
      test. In group 1 (test) no steroids were given. In group 2 20 mg/kg b.m., and in
      group 3 100 mg/kg b.m. dexamethasone was given 2 hrs before CLP. In group 4
      dexamethasone was used in the dose of 20 mg/kg b.m., and in group 3--of 100 mg/kg
      b.m. 8 hrs after CLP. The results of this study show that glycocorticosteroids
      administered during the initial phase of experimental diffuse peritonitis display
      favorable action decreasing animal mortality rate regardless of the dose.
      However, glycocorticosteroids given in the developed septic syndrome decrease the
      pro-inflammatory cytokine serum concentration regardless of the dose, still not
      affecting the animal mortality rate.

PMID- 12053597
TI  - [A case of pseudohypoparathyroidism coexisting with primary hypothyroidism and
      low bone mineral density in relation to age].
AB  - We report a case of 18 year old woman with pseudohypoparathyroidism type la
      presenting with low bone mineral density and primary hypothyroidism. The patient
      was diagnosed because of muscular cramps, accompanied by elevated parathormone
      (PTH) level and hypocalciuria, but normal serum calcium, phosphate and magnesium
      levels. She had features of Albright's osteodystrophy: short stature with normal
      bone age, shortening of IV and V metacarpal bones, and small cerebral
      calcifications shown by CT.

PMID- 12053596
TI  - [Cutaneous larva migrans--an unusual case].
AB  - Cutaneous larva migrans is the result of human skin infestation by nematode
      larvae, which penetrate through the epidermis. The case of 21-year-old woman with
      serpiginous, erythematosus, and linear stripes was reported. The skin lesions
      lasted for five months. The diagnosis of cutaneous larva migrans was established
      based on the typical clinical picture of infestation. Thus, it is important for
      infestation to be recognized clinically, so that effective treatment may be
      instituted. Various therapeutic modalities, including cryotherapy, topical and
      systemic chemotherapy, can be used in the treatment of cutaneous larva migrans.
      It was demonstrated, that cryosurgery is a fast and effective method in the
      therapy of cutaneous larva migrans infestation.

PMID- 12053598
TI  - [Ambras syndrome--a form of generalised congenital hypertrichosis].
AB  - The frequency incidence of generalised congenital hypertrichosis is about 1 to
      billion of people. There are only 4 reported cases of this atavism in Poland from
      Middle Ages. Authors describe 8-months-old infant covered (from birth) with dark,
      delicate hair. The length of the hair ranged from a few millimetres on the
      abdominal region to 5 cm on the back and extremities and 20 cm on head. Eyelids,
      sub orbital regions, ridge and tip of the nose, palms, feet, palmar and lateral
      surfaces of fingers and distal phalanxes were hairless. Especially long hair
      covered pre-temporal and pre-auricular regions, shoulders, spine and extremities.
      Eyebrows were dense and concrescent. Nasal alae and holes were covered with
      lanugo. Ears were covered with long and auditory canals with short hair. The face
      was characterised by hypertelorism, wide nose with horizontal nasal holes.
      Hormonal metabolism was normal. There was no sign of dentition. Skeletal age was
      2 months and psychomotor development--3 months delayed. Upon the basis of above
      mentioned features the Ambras syndrome, which occurred due to a mutation, was
      diagnosed. It is probably the tenth case described since Middle Ages.

PMID- 12053599
TI  - [Fungal allergy. Part I].
AB  - Fungal spores are one of the main groups of allergens. They are present in our
      environment all year long. The concentration of the spores in July and August is
      100-1000 higher than pollens. In contrast with the pollens there is a correlation
      between the spore count and higher risk of medication use, nocturnal asthma
      attacks, and hospitalization rates. We have presented the clinical classification
      of fungi, and characterized main indoor and outdoor allergens. The fungi play
      also an important role in the sick building syndrome. Fungal allergens are not
      only aeroallergens, they may also get into our body with food. They may also
      develop contact reactions. Antibiotic allergy is regarded as one of the classic
      allergic reactions caused by fungi. The id reactions are caused by the fungi from
      far infection focuses.

PMID- 12053600
TI  - [Mucolytics in acute and chronic respiratory tract disorders. I. Pathophysiology
      and mechanisms of action].
AB  - Mucus hypersecretion is a cardinal sign of both acute and chronic pulmonary
      diseases. Normally, mucus protects respiratory tract, but its overproduction
      leads to airway obstruction and promotes bacterial colonization. In the first
      part of our review we outlined the possible factors responsible for mucus
      hypersecretion and clinical consequences of this process. Mucolytic agents such
      as Ambroxol and N-acetylcysteine are able to alter the secretion of mucus and its
      physical properties which results in improvement of mucociliary clearance.
      Mechanisms of action and indications for use of mucolytics are presented.
      Mucolytics have been shown to have a role in improving lung functions and
      patients' quality of life. Undoubtedly they are useful as an adjunctive therapy
      of respiratory tract disorders.

PMID- 12053602
TI  - [Changes in evoked potentials caused in patients with acute stroke (based on
      literature review 1988-1999].
AB  - The CNS neuron excitability and plasticity are objective and measured on the
      basis of the somatosensory (SEP) and motor (MEP) evoked potential (EP) findings.
      The EP examinations are performed in acute stroke (ac-sk) and comatose patients
      (pts) after brain injury. It was tried to check publication frequency of the
      reports in the 1988-1999 years, in Neurologia i Neurochirurgia Polska and in the
      journals registered in the MEDLINE system. The screening meta-analysis was
      conducted of the reported findings. The authors of 23 publications from 16
      countries performed SEP and/or MEP examinations in the 802 ischeamic and 140
      haemorrhagic acute stroke patients. The lesion was accurately localized, the
      immediate and late plasticity was identified and the influence of mannitol on
      penumbra neurons was assessed. The time of active movement recovery and the
      functional improvement of the patients were early and accurately prognosticated.

PMID- 12053601
TI  - [Mucolytics in acute and chronic respiratory tract disorders. II. Uses for
      treatment and antioxidant properties].
AB  - In the first part of our editorial we reviewed the possible factors responsible
      for mucus hypersecretion in acute and chronic pulmonary diseases. The present
      paper presents the results of studies proving, that mucolytics are useful in
      adjunctive therapy of respiratory tract disorders. Mucolytic agents such as
      Ambroxol and N-acetylcysteine are able to alter the secretion of mucus and its
      physical properties which results in improvement of mucociliary clearance.
      Current evidence indicate, that these drugs are effective, especially in chronic
      obstructive pulmonary disease, asthma and acute bronchitis. They produce a modest
      improvement in symptom control and lung function. It has been demonstrated that
      there is a synergism between mucolytics and antibiotics in the treatment of
      exacerbation of chronic bronchitis. Moreover, they act as scavengers of reactive
      oxygen species. Ambroxol is able to inhibit mediator release involved in the
      pathogenesis of allergic inflammation. As mucolytics are cheap and well-tolerated
      they are beneficial in the therapy of patients suffering from respiratory tract
      disorders.

PMID- 12053603
TI  - [Role of gene polymorphism of catechol-O-methyltransferase (COMT), monoamine
      oxidase B (MAOB), cytochrome P450 2D6 (CYP2D6) and N-acetyltransferase 2 (NAT2)
      in pathogenesis of Parkinson's disease].
AB  - Factors underlying pathogenesis of diseases are currently being searched. In
      recent years increasing number of reports on genetic background of central
      nervous system diseases have appeared. In the search of factors that can
      precipitate degeneration of dopaminergic neurons the role of enzymes catabolising
      xenobiotics (CYP2D6, NAT2) and enzymes metabolising catecholamines (COMT, MAO B)
      has been postulated. Polymorphism of genes coding for isotypes characterised by
      different biological activity could be responsible for the propensity for
      Parkinson's disease, progression and efficacy of pharmacotherapy of the disease.

PMID- 12053605
TI  - [Effects of estrogens on the brain and implications for neuro-protection].
AB  - Numerous biological effects of oestrogens within the brain support the argument
      that their influence is not restricted to the reproductive system. Specific
      estrogen receptors were found in the central nervous system as early as in the
      70's, but until recently little was known about the molecular background of
      oestrogens activity in the brain. The last decade witnessed a great effort aimed
      at better understanding of the tangled molecular mechanisms underlying subtle
      liaisons between brain metabolism and cerebral blood flow and particularly their
      disturbances triggered by brain ischaemia. These investigations had an ultimate
      goal--an effective method of preventing an expanding biochemical "catastrophe"
      within and around the ischaemic brain regions (the so-called "neuroprotection").
      Molecular mechanisms by which oestrogens increase both metabolism and blood flow
      through certain regions of the brain became only recently better understood. Now
      there is a consensus as to that these hormones increase secretion of
      neuromediators, stimulate formation of new synapses and can activate certain
      genes, responsible for production of anti-apoptotic proteins and growth factors.
      Oestrogens can also dilate cerebral vessels, here acting through increased
      synthesis of nitric oxide and by stimulating such compounds as prostacycline and
      a potent vasodilator-epoxyeikosotrienoic acid. There is a body of recent evidence
      which suggest that during brain ischaemia the physiological estrogen stimulation,
      of both, brain metabolism and cerebral blood flow, becomes biased towards
      increased release of vasodilating substances. As the metabolism is not spurred
      accordingly, the net effect of oestrogens is neuroprotection. Other protective
      properties of oestrogens within the brain are related to attenuation of the
      excitotoxic effects of glutamate and to the activation of enzymes scavenging free
      oxygen radicals. Moreover, oestrogens can diminish free radicals synthesis and
      act as free radicals scavengers themselves. They can also activate synthesis of
      bcl-2 protein, which prevents cell apoptosis in the ischaemic regions. The
      relevant evidence, which continue to accumulate, may suggest that it is time now
      to consider launching a clinical investigation on the role of oestrogens as
      potentially important neuroprotective factors.

PMID- 12053604
TI  - [Effect of Chlamydia pneumoniae infection on carotid atherosclerosis
      development].
AB  - Recently, a growing number of epidemiological, histopathological and
      microbiological studies have shown that chronic Chlamydia pneumoniae (C.
      pneumoniae) infection accelerates the progression of atherosclerosis of carotid
      and cerebral arteries and thus could constitute a risk factor for stroke. We
      present a number of mechanisms postulated in recent papers that link C.
      pneumoniae infection with the development of atherosclerosis. The one most
      important seems to be the effect of activation of nuclear factor--kappa B and the
      phenomenon of antigenic mimicry between human and C. pneumoniae heat shock
      proteins. We also discuss the problem of immunological reaction against myosin
      filaments of carotid artery wall smooth muscle cells and the problem of antigenic
      mimicry between heavy chains of myosin filaments and antigens presented on C.
      pneumoniae outer membrane.

PMID- 12053606
TI  - [The role of inflammatory reaction in Alzheimer's disease and neurodegenerative
      processes].
AB  - Recent studies state that specific inflammatory mechanisms contribute to
      neurodegeneration. The theory is based on laboratory evidence of local
      upregulation of inflammatory cytokines (ex. IL-1, IL-6), acute phase proteins
      (ex. alpha 1-antitrypsin), activation of the complement cascade and accumulation
      of microglia in damaged regions in AD. In addition epidemiologic studies suggest
      that anti-inflammatory treatment provides some protection from AD. The first
      trials with prednisone fail to show any positive influence in AD patients. The
      alternative therapies are now considered with nonsteroid anti-inflammatory drugs,
      colchicine, cyclophosphamide. The anti-inflammatory treatment gives hope for
      slowing progression of the disease and decline of AD incidence.

PMID- 12053607
TI  - [Use of needle electromyography for diagnosis of radiculopathies].
AB  - Radiculopathy is sometimes evaluated with needle electromyography as additional
      examination to radiographic imaging. The purpose of this study was to determine
      the optimal needle electromyography protocol and the use of needle
      electromyography in the diagnosis of radiculopathy. The authors analysed English
      language writings from years 1981-2000. The selected studies reported a wide
      range of needle EMG abnormalities--from about 30 to 100% of pathological EMGs.
      That is caused by wide variety of patient populations and various EMG protocols.
      EMG of leg muscles in radiculopathy can consist of the assessment of the
      spontaneous activity only or be completed with the assessment of motor unit
      potential (MUP). The EMG of paraspinal muscles assesses spontaneous activity
      only. The number of abnormalities in needle EMG grows with the presence of
      characteristic radiculopathy symptoms, but positive EMG examinations are of
      importance only in cases where diagnosis is complicated. The rate of pathological
      results is higher when needle electromyography is used in the muscles of
      paraspinal region and extremities at the same time. The assessment of the
      spontaneous activity in extremity muscles alone minimizes the influence of error-
      causing factors on the EMG result. Nevertheless lack of assessment of motor units
      potentials makes electromyographic investigation of chronic radiculopathy
      impossible. Sensitivity and specificity of the method have to be determined
      before the clinical use of the assessment of MUP in chronic radiculopathy,
      especially in patients without motor weakness. Needle EMG abnormalities correlate
      with radiological findings in limited range as would be expected from the
      occurrence of radiological findings in asymptomatic patients and overlapping
      innervations of myotomes.

PMID- 12053608
TI  - [Laryngeal dystonia--personal experience with botulin toxin treatment].
AB  - Laryngeal dystonia is a focal dystonia occurring more often than it is diagnosed.
      Adductor type dystonia was described in 5 patients. In 3 cases it manifested
      itself as blepharospasm, which later developed into Meige's syndrome. The
      patients were treated with botulinum toxin A injections under EMG control
      administering 10 i.m. into laryngeal muscles on both sides with good and very
      good results. There were no serious side effects.

PMID- 12053609
TI  - [Cauda equina syndrome caused by Tarlov's cysts--case report].
AB  - Perineural Tarlov cysts located on lumbo-sacral roots can be a cause of cauda
      equina syndrome. OBJECTIVES: 1) To draw attention to the fact that multiple
      Tarlov lumbo-sacral perineural cysts can produce serious movement disturbances.
      2) To document the usefulness of the magnetic resonance imaging in noninvasive
      diagnosis of perineural cysts. CASE DESCRIPTION: A male patient, 80 years of age,
      suffered from progressive weakness of lower limbs, which caused an increasing
      drop of the feet. The disease began in August 2000, following a long journey by
      train. The patient additionally complained of urinary incontinence as result of
      sneezing, coughing or fast walking. The urologist did not find prostatic gland
      hypertrophy. An examination by the internist revealed atheromatous myocardiopathy
      in circulation failure stage. Magnetic resonance imaging showed multiple
      perineural cysts up to 15 mm in diameter on lumbo-sacral roots. This clinical
      picture, supported by the magnetic resonance imaging allowed to recognize cauda
      equina syndrome caused by Tarlov lumbo-sacral perineural cysts. DISCUSSION: This
      case is a reminder, that part of perineural cysts, particularly multiple, can be
      a cause of nerve roots injury, and their lumbo-sacral location can produce cauda
      equina syndrome. As reported by Zarski and Leo, Tarlov cysts were cause of 7.3%
      of pain syndrome cases 2 patients in the study group showed lower limb
      claudication. Magnetic resonance imaging of patients with back pain, performed by
      Paulsen, Call and Murtagh, revealed that Tarlov cysts occurred in 4.6% of
      patients, but only 1% had the symptoms connected with the presence of those
      cysts. In available Polish literature no report has been found referring to fixed
      cauda equina syndrome which was caused by multiple cysts revealed through the
      magnetic resonance imaging of spinal canal. Only Zarski and Leo, discussing the
      correlation between the clinical and radicographic picture, described transient
      cauda equina syndrome in two patients who, beside Tarlov cysts, were also found
      to have intervertebral lumbosacral disc herniation. Tarlov was the first to
      describe well documented cauda equina syndromes caused by cysts on the lumbo
      sacral roots. It is necessary to emphasize the established role of magnetic
      resonance of spinal canal in the diagnosis of perineural cysts on the lumbo
      sacral roots as well as other anatomical anomalies of cerebrospinal fluid spaces.
      Despite the fact that cauda equina syndrome in the case reported here was a
      serious complication of multiple Tarlov cysts in the lumbo-sacral region, a
      surgical treatment was not undertaken; in such cases this treatment should be the
      chosen procedure. CONCLUSION: Multiple perineural Tarlov cysts in lumbo-sacral
      region, without disc herniation or other cause of vertebral canal stenosis, can
      produce cauda equina syndrome.

PMID- 12053610
TI  - [Metachromatic leukodystrophy symptoms in an adult. Case report].
AB  - Metachromatic leukodystrophy is a genetic metabolic disease which generally
      occurs in childhood, surprisingly it can also occur during adulthood. Adult forms
      have very often characteristic presentations with progressive dementia. The
      authors presented a case of metachromatic leukodystrophy in an adult,
      differential diagnosis and examinations which possible made diagnosis.

PMID- 12053611
TI  - [Cystic meningioma: report of three cases].
AB  - Meningioma with cystic component is not a commonly encountered tumor. We report
      three patients with cystic meningioma histologically confirmed. Tomographic
      images of these tumours resembled those of a glial or metastatic origin with
      cystic or necrotic changes and were easily confused. In a 2-year period (1997
      1999) in our Department we had three patients with cystic meningioma who account
      for 5.4% of all patients with meningiomas we have.

PMID- 12053612
TI  - [Report on the Satellite Symposium "Thinking forward--critical problems of
      therapy. 17th Congress ECTRIMS. Dublin (Ireland), 14.09.2001].

PMID- 12053613
TI  - [Micturition disturbances in Parkinson's disease. Clinical and urodynamic
      evaluation].
AB  - Urinary dysfunction in idiopathic Parkinson's disease (IPD) has already been
      described, however its incidence, urodynamic pattern, dependence on the severity
      of parkinsonism as well as improvement with levodopa treatment are not exactly
      known. The aim of the study was to evaluate the frequency of urinary disturbances
      in patients with idiopathic Parkinson's disease and their relationship to
      treatment with levodopa. The investigation was carried out on 41 IPD patients
      aged 37-84 (mean 61.6) years. The neurological examination, including evaluation
      of parkinsonism according to UP-DRS scale was conducted together with the
      urological tests, including uroflowmetry and cystometry. Patients with infection
      of the urinary tract and with prostate hypertrophy were excluded from the study.
      32 (78%) patients had urinary symptoms: frequency in 27 cases (65%), urgency in 9
      cases (21%), urge incontinence in 1 case and dysuria in 1 case. Disorders in
      urodynamic examination were found in 26 cases (63%); they were: detrusor
      hyperactivity in 21 cases (51%), prolonged time of micturition in 18 cases (44%)
      and decrease of maximum flow rate in 19 cases (46%). Detrusor hyperactivity was
      more frequent in patients with extended parkinsonian motor signs. The results of
      the examination indicate frequent urinary disturbances (70%) in IPD, which
      improve during treatment with increased dose of levodopa.

PMID- 12053614
TI  - [Neurological disorders in post-traumatic algodystrophy of the upper extremity].
AB  - Sensory disturbances (hypoaesthesia in fingertips and tenderness) and movement
      disorders (tremor, dystonia, muscle spasms, abnormal postures and inability in
      initiating of movement) were investigated in 80 patients with post-traumatic
      reflex sympathetic dystrophy (RSD) of the upper extremity. Sensory disturbances
      were found in 67 patients (84%): most frequently hypoaesthesia in fingertips--in
      49, and tenderness of the dorsal aspect of the hand in 24; in six patients both
      these signs were present simultaneously. Movement disorders were found less
      frequently: tremor was observed in 12 patients, spasms of the flexor muscles of
      the forearm and hand in two, postural dystonia in one, and inability initiating
      of movement in the other one. Sympathetic interruptions reduced movement
      disturbances in two patients. Dystonia was resistant to various treatment
      approaches including botulinum toxin injections. Certain hypothesis explaining
      pathogenic background of motor and sensory disorders in RSD are discussed. The
      results of this study show that sensory disturbances are frequently observed in
      RSD, however, they usually disappear after successful treatment of the condition;
      movement disorders are less frequent, but much more difficult to control.
      Neurologists are not frequently faced with the problem of neurological disorders
      after trauma of the limb. Inclusion of RSD in differential diagnosis may improve
      recognition of the disorder and result in its faster and proper management.

PMID- 12053615
TI  - [Prognostic factors of long-standing improvement in cervical dystonia, treated
      with botulinum A toxin].
AB  - The clinical improvement after injections of botulinum toxin A in patients with
      idiopathic spasmodic torticollis lasts usually about 3 months. Nevertheless in
      some patients it exceeds several months. The aim of our study was to assess the
      frequency of prolonged response (arbitrally established as > 6 months) and to
      find the possible prognostic factors of such longer effect. In the group of 43
      patients (F30, M13), average age 43.9 (19-72) years, we observed prolonged effect
      in 13 (30.2%). In 5 of them remission was repeated in following sessions (two
      times in four and four times in one). The frequency of spontaneous remissions in
      spasmodic torticollis (12%) is significantly lower than after botulinum toxin,
      what means that they are triggered by drug injection in our group of patients
      with prolonged effect. Within the analysed parameters only the lower average age
      and the average age at the onset of symptoms statistically significantly differ
      in both groups. The authors suggest the possibility of other mechanisms
      responsible for prolonged clinical effect after botulinum toxin: e.g. different
      time of reinnervation (remodelling of synapses) or the modification of natural
      course (feed-back mechanisms) of spasmodic torticollis in some patients.

PMID- 12053616
TI  - [Analysis of causes for falls in people with Parkinson's disease].
AB  - Falls in Parkinson's disease may pose a significant threat for patients. This is
      not only a clinical problem, but also an economic one. The effects of falls may
      cause deterioration of the quality of life for both patients and their
      caretakers. The causes of falls are not clinically uniform: the falls are caused
      by various factors and require a differential diagnosis. The purpose of this
      paper is to analyse the above mentioned causes, as well as to draw clinicians'
      attention to the possibility of effective therapy for certain disorders that
      cause such falls in patients with Parkinson's disease. 51 patients with
      recognized Parkinson's disease were examined, including 25 persons who reported
      falls that had occurred within the past 6 months and 26 persons who had no falls.
      In both groups there were patients with different types of the disease
      (tremulous, akinetic-hipertonic and mixed). The clinical status of the patients
      was assessed using the Hoehn and Yahr scale. In each patient Schellong test and
      EEG examinations were performed. It has been established that the occurrence of
      falls is related to the duration of the disease (on average 9.6 years in the
      group with falls versus 6.2 years in the group without falls) and the daily
      levodopa dosage (on average 806.0 mg in the group with falls versus 499.0 mg in
      the group without falls). The proportion of patients with abnormalities in the
      EEG (revealed mainly as slowing of EEG background activity) was notably higher in
      the group with falls. The comparison of such groups from the point of view of
      sex, age, stage of the disease and the occurrence of asymptomatic orthostatic
      hypotension did not reveal any statistically significant differences. The
      analysis of the causes of falls in the examined patients revealed that in 8 cases
      they fell due to unstable posture, 4--due to freezing or festination, 1--due to
      symptomatic orthostatic hypotension, 1--due to co-existing neurological
      disorders, 2--due to the heart arrhythmia (requiring implantation of pacemaker),
      in 8 persons--due to toppling falls and in 1 patients the falls could not be
      classified.

PMID- 12053617
TI  - [Prognostic value of the Knosp scale in trans-sphenoidal surgery for pituitary
      adenomas].
AB  - Various surgical approaches are available for the treatment of somatotroph
      pituitary adenomas. The treatment of choice remains surgical excision via
      transsphenoidal route. The results of that operation depend on the volume of the
      tumour, its suprasellar and parasellar extension, especially to the cavernous
      sinus. Modern neuroimaging by magnetic resonance provides visualization of the
      size and extension of the tumour, but invasion of the cavernous sinus space
      remains still a surgical diagnosis. According to intraoperative observations and
      proliferation marker (Ki-67) Knosp has evolved out radiological classification
      describing parasellar extension of pituitary adenomas. We present a series of 142
      somatotroph pituitary adenomas surgically treated by transsphenoidal route. The
      radiological features of the tumours are described using Knosp classification.
      The results of surgery are analyzed with special reference to preoperative
      magnetic resonance findings. We found Knosp scale useful for prognostic
      classification for transsphenoidal surgery cases.

PMID- 12053618
TI  - [Determination of brain death].
AB  - We present diagnostic criteria of brain death determination that were
      determinated by physicians based on physical signs, "tests of death" and
      confirmatory tests. All standards required by Polish law are also presented and
      discussed. They are compared with recent guidelines published by American Academy
      of Neurology. Confirmatory tests that are not required by law in Poland are also
      emphasised. They appear to be of great worth for cases in whom physical signs
      cannot be reliably interpreted. The aim of this article is to present how the
      definition of death was being changed for the centuries and what kinds of
      requirements the law in Poland needs at the beginning of the XXI century.

PMID- 12053619
TI  - Shared mental health care. The way ahead.

PMID- 12053620
TI  - MAINPRO. Self-regulation, professionalism, and continuing professional
      development.

PMID- 12053621
TI  - Health care just a phone call away.

PMID- 12053622
TI  - Volunteer clinic for the uninsured.

PMID- 12053623
TI  - Time to establish a successful model.

PMID- 12053624
TI  - Time to establish a successful model.

PMID- 12053625
TI  - Time to establish a successful model.

PMID- 12053626
TI  - Treating persistent cough: caution!

PMID- 12053627
TI  - What is the role of walk-in clinics?

PMID- 12053628
TI  - What is the role of walk-in clinics?

PMID- 12053629
TI  - De facto evidence for the no-stirrup method.

PMID- 12053630
TI  - Bacterial vaginosis during pregnancy. Should we screen for and treat it?
AB  - QUESTION: Some of my patients have been diagnosed with bacterial vaginousis (BV)
      during pregnancy; some have symptoms, others do not. Should I be treating them,
      and if so, with what? Also, should I be screening all my pregnant patients for
      BV? ANSWER: There appears to be no benefit to screening or treating pregnant
      women with an average risk of BV. It is not even clear that treating pregnant
      women at high risk of BV is beneficial. If you decide to treat, the drugs of
      choice are oral or intravaginal gel metronidazole or oral clindamycin. Both these
      drugs are safe to use throughout pregnancy.

PMID- 12053631
TI  - Ophthaproblem. Pseudopapilledema.

PMID- 12053632
TI  - Who is using the drugs I prescribe?

PMID- 12053633
TI  - Who needs an endometrial biopsy?

PMID- 12053634
TI  - Bipolar spectrum disorders. New perspectives.
AB  - OBJECTIVE: To review new perspectives on diagnosis, clinical features,
      epidemiology, and treatment of bipolar II and related disorders. QUALITY OF
      EVIDENCE: Articles were identified by searching MEDLINE and ClinPSYCH from
      January 1994 to August 2001 using the key words bipolar disorder, type II or 2;
      hypomania; spectrum; or variants. Reference lists from articles were reviewed.
      Overall, the quality of evidence was not high; we found no randomized controlled
      trials that specifically addressed bipolar II or bipolar spectrum disorders
      (BSDs). MAIN MESSAGE: Characterized by elevated mood cycling with depression,
      BSDs appear to be much more common than previously thought, affecting up to 30%
      of primary care patients presenting with anxiety or depressive symptoms.
      Hypomania, the defining feature of bipolar II disorder, is often not detected.
      Collateral information, semistructured interviews, and brief screening
      instruments could improve diagnosis. Antidepressants should be used with caution.
      The newer mood stabilizers or combinations of mood stabilizers might be the
      treatments of choice in the future. CONCLUSION: Family physicians, as primary
      providers of mental health care, should try to recognize and treat BSDs more
      frequently. These disorders are becoming increasingly common in primary care
      populations.

PMID- 12053635
TI  - St John's wort or sertraline? Randomized controlled trial in primary care.
AB  - OBJECTIVE: To compare the change in severity of depressive symptoms and
      occurrence of side effects in primary care patients treated with St John's wort
      (SJW) and sertraline. DESIGN: Double-blind, randomized 12-week trial. SETTING:
      Community-based offices of 12 family physicians practising in greater Montreal,
      Que. PARTICIPANTS: Eighty-seven men and women with major depression and an
      initial score of > or = 16 on the Hamilton Rating Scale for Depression (Ham-D).
      INTERVENTIONS: Patients were randomized to treatment with either sertraline (50
      to 100 mg/d) or SJW (900 to 1800 mg/d) in a double-blind fashion. Assessment of
      depression was done at entry and at 2, 4, 8, and 12 weeks using the Ham-D, the
      Beck Depression Inventory (BDI), and a questionnaire asking about compliance and
      side effects. MAIN OUTCOME MEASURES: Changes from baseline in Ham-D and BDI
      scores and self-reported side effects. RESULTS: There were no important
      differences in changes in mean Ham-D and BDI scores (using intention-to-treat
      analysis), with and without adjustment for baseline demographic characteristics,
      between the two groups at 12 weeks. Significantly more side effects were reported
      in the sertraline group than in the SJW group at 2 and 4 weeks' follow up.
      CONCLUSION: The more benign side effects of SJW make it a good first choice for
      this patient population.

PMID- 12053636
TI  - Caring for seriously mentally ill patients. Qualitative study of family
      physicians' experiences.
AB  - OBJECTIVE: To examine family physicians' experiences in caring for patients with
      serious mental illness and their expectations of a shared mental health care
      (SMHC) model. DESIGN: Qualitative method of in-depth interviews. SETTING: London,
      Ont. PARTICIPANTS: Purposive sample of 11 full-time family physicians providing
      ongoing care for patients with serious mental illness. METHOD: Eleven interviews
      were conducted to explore family physicians' experiences. All interviews were
      audiotaped and transcribed verbatim. Analysis was done using a constant
      comparative approach and was carried out concurrently rather than sequentially.
      Researchers read all interview transcripts independently before comparing and
      combining their analyses. Final analysis involved examining all interviews
      together to discover relationships between and among emerging themes. MAIN
      FINDINGS: Findings reflected three main themes: what family physicians perceive
      they bring to care of seriously mentally ill patients (i.e., whole-person
      approach to care); challenges family physicians face in participating in shared
      care of these patients (i.e., communication and access issues); and family
      physicians' expectations of a SMHC model (i.e., guidance and feedback).
      CONCLUSION: As seriously mentally ill patients are moved out of institutions, the
      need for an effective and efficient SMHC model becomes imperative. Our findings
      suggest that family physicians could be an important part of SMHC models but only
      if systemic barriers are removed and collaborative practice is encouraged.

PMID- 12053637
TI  - Family physicians and psychiatrists. Qualitative study of physicians' views on
      collaboration.
AB  - OBJECTIVE: To understand how to improve collaboration between psychiatrists and
      family physicians in primary care settings. DESIGN: Qualitative study using 10 in
      depth interviews and a focus group session. SETTING: Catchment area in eastern
      Montreal, Que. PARTICIPANTS: Five FPs and five psychiatrists. METHOD: Ten
      interviews and a focus group were conducted to identify ways of improving
      collaboration between FPs and psychiatrists. All session were audiotaped and
      transcribed verbatim. Analysts used Atlas.ti to compare findings vertically and
      horizontally. MAIN FINDINGS: Three strategies were identified: communication,
      continuing medical education (CME) for FPs, and access to consulting
      psychiatrists. The first two can be implemented by FPs and psychiatrists
      together, but psychiatrists thought the last one was not feasible due to lack of
      both time and remuneration for such activity. CONCLUSION: Better communication
      and CME for FPs in psychiatry can help improve collaboration between FPs and
      psychiatrists. Increased access to consulting psychiatrists requires substantial
      alteration in established clinical roles and routines.

PMID- 12053639
TI  - Shared mental health care. Update from the Collaborative Working Group of the
      College of Family Physicians of Canada and the Canadian Psychiatric Association.

PMID- 12053640
TI  - Transatrial access to the normal pericardial space for local cardiac therapy:
      preclinical safety testing with aspirin and pulmonary artery hypertension.
AB  - The reliability, rapidity, and safety of nonsurgical, transatrial pericardial
      access for local cardiac therapy have been demonstrated in healthy animals. Since
      many patients take aspirin or have increased right-sided pressures, we evaluated
      the procedure's safety under these conditions. Transatrial pericardial access was
      performed in anesthetized pigs following aspirin administration (162 mg p.o., n =
      6) or during experimental pulmonary artery hypertension (n = 4 different animals)
      and required only 3 minutes following guide catheter positioning. Platelet
      aggregability testing with arachidonic acid confirmed aspirin effectiveness. Mean
      pericardial fluid hematocrit was 0.1 +/- 0.1% after 2 days of aspirin therapy and
      1.9 +/- 1.1% at sacrifice 24 hours later (NS). Mean pericardial fluid hematocrit
      was 1.0 +/- 0.5% after 45 minutes of pulmonary artery hypertension and 4.3 +/-
      0.8% at sacrifice 30 minutes later (NS). Histologic analysis in both groups
      revealed a small thrombus and localized inflammation at the site of puncture.
      Neither aspirin use nor pulmonary artery hypertension causes significant bleeding
      into the pericardial space following transatrial access and thus does not
      preclude this route for local cardiac drug delivery.

PMID- 12053641
TI  - Measurement of fractional flow reserve to assess moderately severe coronary
      lesions: correlation with dobutamine stress echocardiography.
AB  - BACKGROUND: New techniques to evaluate coronary artery disease, such as
      calculation of myocardial fractional flow reserve (FFR) with a guidewire and
      pressure transducer, provide a functional assessment of coronary lesions. The
      present study was designed to determine the correlation between FFR and
      dobutamine stress echocardiography in patients with moderately severe coronary
      stenosis in order to judge the usefulness of FFR for commonly encountered
      clinical problems. METHODS AND RESULTS: We studied 21 patients with 23 moderately
      severe coronary artery stenoses on angiography. The FFR was calculated and
      dobutamine stress echocardiography was performed to detect ischemia. Of the 16
      stenoses with a negative FFR (> or = 0.75), dobutamine echocardiography also was
      negative. In the seven stenoses with a positive FFR (< 0.75), dobutamine
      echocardiography was positive in three. The efficacy of FFR in detecting ischemia
      that was confirmed with stress echocardiography was sensitivity 100%, specificity
      80%, positive and negative predictive value 42.8%, and 100%, respectively, with a
      global predictive value 82.6%. A moderate degree of correlation was found between
      the two diagnostic tests (kappa [kappa] = 0.51). CONCLUSIONS: FFR correlates
      moderately well with dobutamine stress echocardiography in the assessment of
      moderately severe lesions in patients for whom coronary arteriography is usually
      indicated. However, its high negative predictive value makes FFR a useful aid in
      reaching clinical decisions promptly in the hemodynamics laboratory.

PMID- 12053638
TI  - Prevention of group B streptococcal infection in newborns. Recommendation
      statement from the Canadian Task Force on Preventive Health Care.

PMID- 12053643
TI  - Therapeutic angiogenesis in critical limb and myocardial ischemia.
AB  - Research in animal models of ischemia has shown that administration of angiogenic
      growth factors, either as a recombinant protein or by gene transfer, can augment
      nutrient perfusion through neovascularization to promote the development of
      supplemental collateral blood vessels that will constitute endogenous bypass
      conduits around occluded native arteries; a strategy termed "therapeutic
      angiogenesis." In animal models and clinical trials, the best studied cytokines
      with angiogenic activity are vascular endothelial growth factor (VEGF) and
      fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in
      patients with critical limb ischemia demonstrated resolution of rest pain and/or
      improved limb integrity, increased pain-free walking time and ankle-brachial
      index, newly visible collateral vessels by digital subtraction angiography, and
      qualitative evidence of improved distal flow by magnetic resonance imaging.
      Initial clinical trials in patients with end-stage coronary artery disease using
      direct myocardial injection via thoracotomy resulted in large increases in
      exercise time and marked reductions in anginal symptoms, as well as objective
      evidence of improved perfusion and left ventricular function. Larger scale
      placebo-controlled trials have been limited to intracoronary and intravenous
      administration of recombinant protein, and have not shown significant improvement
      in exercise time or angina compared to placebo. Larger scale placebo-controlled
      studies of gene transfer using catheter-based endocardial delivery are in
      progress. Future clinical studies are required to determine the optimal dose,
      formulation, route of administration, and combinations of growth factors, as well
      as the requirement for endothelial progenitor cell or stem cell supplementation,
      to provide effective and safe therapeutic angiogenesis for patients with critical
      limb ischemia and chronic myocardial ischemia who are not candidates for
      conventional revascularization procedures.

PMID- 12053642
TI  - Clinical management of patients with coronary syndromes and negative fractional
      flow reserve findings.
AB  - AIMS: New interventional techniques to diagnose coronary artery stenosis, such as
      calculation of myocardial fractional flow reserve (FFR) with a guidewire and
      pressure transducer, provide a functional assessment of coronary lesions. The
      present study was designed to investigate the occurrence of cardiac events in
      patients with coronary syndromes and negative FFR findings in moderately severe
      coronary stenosis in order to determine the usefulness of this technique in
      predicting coronary events during follow-up for problems commonly encountered in
      clinical practice. A further objective was to evaluate the safety of deferring
      angioplasty in patients with a negative FFR result. METHODS: We studied 43
      patients with 44 moderately severe coronary artery stenoses on angiography and
      FFR > or = 0.75. Mean age of the patients was 58 +/- 11.4 years. The indications
      for coronary angiography included recent unstable angina in 24 (55.8%) patients,
      recent acute myocardial infarction in 10 (23.2%) patients, 5 (11.6%) patients
      with a coronary stent who had symptoms of uncertain cause, and stable angina in 4
      (9.3%) patients. RESULTS: During a mean follow-up period of 10.7 +/- 5.9 months,
      clinical events (unstable angina) occurred in five patients. In three patients,
      the initially investigated artery was involved, and in the two patients who
      required coronary revascularization, unstable angina was related with an artery
      different from the one studied initially. CONCLUSIONS: Patients with recent
      coronary syndromes and negative FFR findings in moderately severe coronary
      stenosis were unlikely to have cardiac events during a 10-month follow-up period.
      Our findings suggest that FFR is a potentially useful indicator of the likelihood
      of cardiac events and thus represents a useful aid in clinical decision-making in
      the hemodynamics laboratory. This diagnostic technique also is potentially useful
      in identifying patients for whom angioplasty can be safely deferred.

PMID- 12053644
TI  - Clinical evaluation and options for infrainguinal atherosclerosis therapy: when
      to intervene?
AB  - Cardiologists have gained considerable experience and expertise in the diagnosis
      and management of coronary artery disease. Interventional therapy has now become
      a standard cornerstone of therapy for coronary artery disease, and endoluminal
      stents are being used in over 70% of all coronary interventions. Diagnosis and
      treatment of peripheral arterial disease (PAD) has recently gained momentum. In
      the past, vascular surgeons and interventional radiologists were the classic
      caregivers for PAD patients, with an interest in deciding between intervention or
      no intervention. In addition, the majority of PAD patients had few medical
      resources since many medical specialists did not view PAD as important for many
      reasons, such as: (1) few effective options for the management of patients with
      PAD, (2) PAD did not represent a significant health hazard to patients, (3) few
      patients actually suffered from PAD, and (4) patients did not view PAD as a
      significant limitation in their quality of life. Over the past decade, a new
      medical specialty, vascular medicine, had dedicated itself to the comprehensive
      management of these complex patients. Vascular medicine specialists are
      predominantly internists and cardiologists. These physicians not only view PAD as
      an important medical issue, they understand the increasing prevalence of PAD
      among the "baby-boomer" generation, the shortened life-expectancy of patients
      with PAD, and the marked reduction in the quality of life among PAD patients.
      Most importantly, vascular medicine physicians are now aware of several effective
      options for patients with PAD.

PMID- 12053645
TI  - Percutaneous arterial aortoiliac intervention.
AB  - Historically reconstructive vascular surgery, has been a cornerstone of treatment
      for symptomatic obliterative aortoiliac disease. Surgical results include a
      reported aortobifemoral bypass 5-year patency rate from 85% to 90% and a 10-year
      patency rate of 70% to 75%. Operative mortality for aortoiliac reconstruction
      ranges from 1.6% to 3.3%, with an aggregated systemic morbidity of 8.3%. Clinical
      indications for surgical intervention are well-established and are limited
      primarily to severe claudication and limb-threatening ischemia. Broader
      application of surgical intervention is not recommended because of significant
      morbidity and mortality associated with the procedure. As balloon angioplasty and
      endovascular stenting technologies evolve, they are proving to be an effective
      modality for the treatment of aortoiliac disease. These lower risk procedures
      have allowed expansion of traditional indications for intervention. Treatment is
      recommended presently for patients with clinical symptoms that impact lifestyle
      and professional requirements. Less conventional indications include allowing
      access for coronary intervention or for placement of an intra-aortic balloon
      pump, or improving inflow prior to a distal surgical bypass procedure. Results of
      aortoiliac percutaneous interventions are difficult to compare with surgical data
      since methods and technology continue to improve and evolve, and randomized
      studies are limited. It is clear that as long as outcomes of percutaneous
      interventions are predictable and secondary patency rates acceptable, the low
      complication rates of a percutaneous intervention are clearly preferable to a
      riskier surgical alternative.

PMID- 12053646
TI  - The management of acute limb ischemia: techniques for dealing with thrombus.
AB  - Acute limb ischemia (ALI) has long been a major clinical problem, producing
      significant risks for limb loss and death. It is most commonly caused by arterial
      thrombosis in the setting of underlying atherosclerotic peripheral vascular
      disease or by arterial embolism, usually of cardiac origin. Over the past several
      decades, preferred treatment options for ALI have alternated between medical and
      surgical approaches. More recently, direct intra-arterial thrombolysis became the
      standard of care after several randomized trials demonstrated the benefit of this
      approach as compared with acute surgical intervention. Despite all of the
      experience with direct intra-arterial thrombolysis for the treatment of ALI, the
      optimal thrombolytic approach not been clearly established. Current investigation
      is directed at identifying the ideal thrombolytic agent for this purpose and the
      appropriate dosing regimen. In addition, there is interest in the newer
      mechanical thrombectomy devices and the use of platelet glycoprotein IIb/IIIa
      inhibitors to speed the time to reperfusion of the acutely ischemic limb.

PMID- 12053647
TI  - Prediction and prevention of contrast nephropathy.
AB  - Over the last 10 years, the main advances in RCN have come in our ability to
      predict outcomes for an individual patient. Treatment trials have been almost all
      uniformly disappointing. Recent positive trials with acetylcysteine and PGE1 will
      require confirmation in larger trials that are adequately powered for meaningful
      end points in the PCI population. In the meantime, adequate prehydration and
      maintenance of post-PCI urine flow rates of > 150 mL/min remain the most prudent
      measures. As the population ages, breakthroughs with respect to new contrast
      agents or effective prevention measures will be needed to offer PCI to the
      spectrum of patients at risk for renal injury.

PMID- 12053648
TI  - Aggressive secondary prevention: a perspective from the coronary interventional
      setting.

PMID- 12053649
TI  - Balloon angioplasty.

PMID- 12053650
TI  - [Role of epileptogenic lesions in the development of ictal and interictal
      epileptic disturbance].
AB  - The most common cause of focal epilepsies is the morphological brain abnormality,
      the epileptogenic lesion. Nowadays, by using MRI, the epileptogenic lesion can be
      demonstrated in vivo in more and more cases. Our knowledge regarding the clinical
      and pathophysiological features of epilepsy should be reevaluated in the
      highlight of the epileptogenic lesions demonstrated by MRI. The presence and the
      type of the epileptogenic lesion are important prognostic factors in the
      pharmacological and surgical treatments of epilepsy. Because the localization of
      the lesion is usually identical with the site of the seizure onset, the MRI
      investigation play an important role not only in identifying the epilepsy
      etiology but also in the non-invasive localization of the epileptic focus.
      Tumors, malformations of the cortical development, the hippocampal sclerosis,
      perinatal lesions, posttraumatic scars and the vascular malformations are the
      most important morphological abnormalities associated with epilepsy. Low-grade
      astrocytoma, pilocytic astrocytoma, oligodendroglioma, ganglioglioma, and the
      dysembrioplastic neuroepithelial tumors are the most common neoplasms associated
      with chronic epilepsy. Low grade astrocytomas or vascular malformations generate
      seizures due to chemical or mechanical effects of the lesion, the pacemaker area
      occurs obviously outside the lesion, in the adjacent brain tissue. Conversely,
      malformations of cortical development have intrinsic epileptogenicity. In them,
      the seizure onset zone is localized intralesional: the lesion generates seizures
      itself.

PMID- 12053651
TI  - [Plasticity of tissue stem cells].
AB  - In the early stages of embryonic development, cells have the capability of
      dividing indefinitely and then differentiating into any type of cell in the body.
      Recent studies have revealed that much of this remarkable developmental potential
      of stem cells is retained by small populations of cells within most tissues in
      the adult. Intercellular signals that control the proliferation, differentiation
      and survival of tissue stem cells in their niches are being identified and
      include a diverse array of morphogens, cytokines, chemokines and cell adhesion
      molecules. Adult tissue stem cells, moreover, can also differentiate into
      developmentally unrelated cell types, such as nerve stem cells into blood cells.
      Currently, we can only speculate about the mechanisms involved in such dramatic
      changes in cell fate. For example, the emergence of, say, hematopoietic stem
      cells from brain neurospheres could involve either transdifferentiation (brain-
      >blood) or dedifferentiation (brain-->pluripotent cells), or by the actions of
      rare, but residual pluripotent stem cells. This issue is central to understanding
      the molecular basis of commitment and lies at the heart of debates about
      plasticity and the reversibility of developmental restriction.

PMID- 12053652
TI  - [Experience with laser in situ keratomileusis].
AB  - AIM OF THE STUDY: To evaluate the results of laser in situ keratomileusis (LASIK)
      in groups with different refractive errors. PATIENTS AND METHODS: 68 LASIK
      procedure have been performed in the following patient groups: Group 1 (-3.0 D to
      -6.0 D) n = 14; Group 2 (-6.25 D to -9.0 D) n = 29; Group 3 (-9.25 D to -14.0 D)
      n = 13; Group 4 (eyes with hyperopic refractive error between +1.75 D and +7.5 D)
      n = 12. A Moria CB manual mikrokeratom was used, flap thickness was 130 microns.
      Excimer laser treatment was carried out with Asclepion-Meditec MEL 70 G-Scan
      flying spot excimer laser. Follow-up time is 6 months. RESULTS: The preoperative
      correction decreased in Group 1. from -4.45 D +/- 0.93 D (SE = spherical
      equivalent) to -0.04 D +/- 0.13 D, in Group 2. from -7.81 D +/- 0.98 D (SE) to 
      0.56 D +/- 0.9 D, in Group 3. from -11.33 D +/- 1.97 D (SE) to -1.88 D +/- 1.64
      D, and in Group 4. from +4.67 D +/- 1.67 D (SE) to +0.24 D +/- 0.50 D 6 months
      following LASIK. The best spectacle corrected visual acuity (BSCVA) decreased by
      2 or more Snellen lines in 4 eyes in Group 2, in 2 eyes in Group 3, and there was
      no change in Group 1 and Group 4. BSCVA improved by 2 or more Snellen lines in
      one eye in Group 2, in 2 eyes in Group 3 and there was no change in Group 1 and
      in Group 4. CONCLUSIONS: The preoperative correction decreased significantly
      following LASIK procedure in each patient group. The method was found to be
      effective, safe and durable during the 6 months follow-up. Application is
      recommended especially in eyes with a refractive error higher than -6.0 D due to
      possible intra- and early postoperative complications.

PMID- 12053653
TI  - [Mor Kaposi (1837-1902)--after 100 years].

PMID- 12053654
TI  - [Centenary of the St.Gyorgy Hospital in Fejer County (1901-2001)].

PMID- 12053655
TI  - [Embryonal rhabdomyosarcoma of the nasopharynx in a 3-year old girl].
AB  - A case of rhabdomyosarcoma embryonal of the nasopharynx in a 3-year-old girl has
      been described. Clinical manifestations and initial diagnostic difficulties
      resulting in delay of proper diagnosis were discussed. Division of RMS, etiology,
      differentiation of the most often applied clinical sign and modern therapeutic
      opportunities depending on the location, histopathological type, the disease
      advancement level and the patient's age were described. Late outcome and the
      initially positive results of the employed treatment were emphasized in the
      presented case. The authors would like to underline the necessity to apply all
      imaging methods available (CT scan and MRI), in order to determine the exact site
      and extensiveness of malignancy which is crucial for evaluation of appropriate
      treatment and therapy.

PMID- 12053656
TI  - [A case of inverted papilloma of the nose and sinuses].
AB  - Two cases of inverted papilloma with unilateral nasal obstruction since 2 years,
      bleeding from the nose and headache are described. Surgical treatment was
      applied. Histological examination revealed inverted papilloma.

PMID- 12053658
TI  - [Tuberculosis of the inner ear].
AB  - Tuberculosis of the middle ear is a rare, but not a nonexistent disease. It is
      well reported in literature that the typical features of this disease have been
      changing over the years, what can lead to delay in proper diagnosis and cause
      irreversible complications. Presented two cases of tuberculous otitis media
      confirm the opinion that historically classical triad of features: painless
      otorrhea, multiple perforations of the tympanic membrane and concomitant
      peripheral facial paralysis is often absent in the clinical picture of this
      disease.

PMID- 12053657
TI  - [Endothelin-1 and bradykinin in nasal lavage fluid of patients allergic to tree
      pollen].
AB  - Hay fever is one of the most frequent upper airway diseases. The nasal epithelium
      is considered to play and active role in the allergic inflammation through its
      capacity to synthesize and release a wide range of cytokines and mediators. One
      substance of potential relevance in this regard is endothelin (ET). We postulated
      that ET-1 could contribute to pathomechanism of seasonal allergic rhinitis. The
      aim of this study was to demonstrate release of this peptide and bradykinin into
      the nasal lavage fluid (NLF) of tree pollen allergic patients in response to
      allergen challenge. 16 subjects aged 25.5 +/- 3.3 years with clinical history of
      tree pollen allergic rhinitis participated in the study. Nasal allergen
      provocation with following lavage was performed in all subjects. Ten of them were
      hyposensitized preseasonally by allergic vaccine Allergovit (Allergopharma,
      Germany). Six patients received treatment with antihistamines, cromoglicates or
      steroids. Bradykinin and endothelin-1 in the nasal secretion were assayed before
      starting immunotherapy and early during tree pollen season. Increase in
      concentration of bradykinin in nasal lavage fluid from hyposensitized patients
      were significantly lower than from second group, 509.4 +/- 110.4 before 942.9 +/-
      234.89 pg/ml after allergen provocation versus 417.8 +/- 100.4 and 2001.6 +/-
      223.6 pg/ml (p < 0.05). We noticed lower concentration of ET-1 in NLF of hay
      fever patients, 17.5 +/- 3.9 versus 13.9 +/- 2.7 pmol/ml. We conclude that
      bradykinin and endothelin-1 could be involved in the pathogenesis of hay fever.

PMID- 12053659
TI  - [Professional medical expressions collected during Kronlein's orbitotomy].
AB  - The paper analyses medical expressions which are refered to as professional
      terms. The lexical data were collected during performing orbitotomy. The authors
      confirm the necessity and usefulness of the application by medical staff of brief
      statements, usually confined to one word or phrase which conveys the main
      meaning.

PMID- 12053660
TI  - [Evaluation of the vestibular apparatus in children with diabetes mellitus type
      1].

PMID- 12053661
TI  - [Expression of E-cadherin and CD44 in laryngeal cancer].

PMID- 12053662
TI  - [Evaluation of vocal cords with electroglottographic examination].

PMID- 12053663
TI  - [Epidemiologic analysis of patients with laryngeal and hypopharyngeal cancer
      treated in the Department of Otolaryngology in Bialystok from 1986-1999].
AB  - Epidemiological analysis of patients with the larynx cancer, who were treated in
      the Department of Otolaryngology in Bialystok from 1996 to 1999 was performed.
      The following aspects were assessed: a) number of patients, b) gender, c) age, d)
      place of living, e) primary site of the tumour. The results in years 1996-1999
      were compared with the earlier published results in years 1986-1994. Altogether
      1431 patients (1340-93.6% males and 91-6.4% females) in that period and there
      were similar numbers of hospitalizations every year. Among patients there were 28
      33% farmers, 41-46% labourers, 5-9% white collar workers, the others were old age
      pensioners. 55-59% patients came from the rural areas and 41-45% patients from
      urban areas. The most common site of the primary tumour was the supraglottic
      region (831-58.1%), then glottis (421-29.4%) and rarely in the subglottic region
      (5-0.3%). Hypopharynx was the tumor primary site in 174 (12.2%) patients. The
      analysis showed that the numbers of patients with cancer of the larynx or
      hypopharynx are similar in each year. A constant increase in number of female
      patients; coming from the rural area, farmers or labourers was found. Increasing
      incidence rate of supraglottic tumours and little decrease in the number of
      glottic tumours were also found.

PMID- 12053664
TI  - [Rhinitis in patients with cystic fibrosis].
AB  - The author presents material of 110 cystic fibrosis patients, 81 with typical
      clinical features and 29 with atypical phenotype. Based on clinical examination
      and nasal cytological smears infective chronic nonspecific rhinitis (n = 80),
      infective acute rhinitis (n = 16), perennial allergic rhinitis (n = 4),
      nonalergic rhinitis with eosinophilia (n = 2), and moreover 19 patients with
      nasal polyposis, and 8 patients without nasal symptoms were distinguished.
      Infective chronic nonspecific rhinitis and infective acute rhinitis were present
      in typical and atypical cystic fibrosis patients with similar frequency but in
      patients with atypical phenotype perennial allergic rhinitis and nonalergic
      rhinitis with eosinophilia were observed more frequently. Nasal polyposis was
      associated with typical cystic fibrosis phenotype, and with two "severe"
      mutations.

PMID- 12053665
TI  - [Effect of ultrasonography on postoperative changes in treatment of neck lymph
      nodes and improvement of long term results in patients with laryngeal neoplasms].
AB  - Ultrasonography (US) is a well-known and valuable method of detecting lymph nodes
      in the neck. It is widely used in the preoperative neck assessment and in follow
      up patients treated for head and neck cancer. The aim of the study was to compare
      the larynx cancer patients in two decades: the 80-ies and the 90-ies and the
      influence of a single diagnostic tool, i.e. ultrasonography, on therapeutic
      decisions and final results. Two groups of patients were selected: 737 patients
      treated between 1981-1985 (before the introduction of US) and 840 patients
      treated between 1991-1995 (routinely examined with the help of US) in ENT Dept.
      of Karol Marcinkowski University of Medical Sciences in Poznan. We aimed at
      analysing the percentages of neck metastases at the moment of diagnosis, the
      frequency of particular types of primary neck treatment, the percentages of neck
      recurrences, their advancement at the diagnosis and the methods of secondary
      treatment. Particular attention to feasibility of salvage was paid. Mean survival
      time in the group of patients with recurrence and the overall 5-year-long
      survival rates were analysed. No marked differences were stated between both
      groups as to epidemiological data, primary tumor advancement and types of the
      performed larynx surgery. Neck metastases occurred in both groups, 34% and 42%,
      respectively. Relapse rates were 12.9% and 12.6%, respectively. It was found that
      the number of elective neck dissections over the period given above became
      smaller, the number of radical neck dissections was stable, while the number of
      patients referred to wait and see policy increased. The number of successful neck
      salvage surgeries markedly increased while the number of patients not qualified
      for salvage decreased. For the both studied data, the curves on diagrams cross
      around the year 1992. The turning point situated in this time shows that
      ultrasound, introduced in 1991, gradually changed the types of primary treatment
      and possibilities of salvage neck treatment. The statistically significant
      differences in both groups were shown as to: types of the initial i.e. first neck
      treatment, relapse rate and the possibility of performing surgical salvage, while
      the only change was the introduction of a new diagnostic tool, i.e. neck
      ultrasonography. Survival rate was markedly better in the second group of
      patients. The methods of qualifying patients for the primary neck treatment and
      follow-up schedule have been changed since ultrasonography diagnostics was
      introduced in 1991 for routine assessment of the neck lymphatics in the larynx
      cancer patients. Strict follow-up schedule allow for early detection and
      successful treatment in high percentage of relapses.

PMID- 12053666
TI  - [Anastomosis of hypoglossal-facial nerves by modified May technique].
AB  - Facial palsy is a unpleasant disorder, which handicaps habitual vital movements
      and the expression of the face. There are many surgical techniques, which use the
      neighboring nerve fibers to reanimate the face, such as the end to end or side to
      end anastomosis with hypoglosal, glosopharyngeal, axesorius, or mandibular
      nerves. The donor fiber can be derived from homolateral or heterolateral side.
      The reconstruction can be completed by cosmetic surgery using parietal muscle or
      free muscular flaps. The authors wanted to present the modified May technique
      described by Darrouzet with the rerouting of the facial nerve in the mastoid
      portion of the temporal bone. This procedure aimed at elongation of the facial
      nerve stumps with simultaneous rerouting of the facial nerve. Three temporal bone
      blocks with adjacent tissues were taken from cadavers. The temporal bones were
      dissected under operating microscope ZEISS OPM 11. The standard set of
      instruments for the ear microsurgery was used. As the first step retroauricular
      incision and large antromastoidectomy were performed. The facial nerve was found
      and exposed in its mastoid portion, then rerouted out of the temporal bone. The
      length of the isolated nerve stump was measured. The photos were also taken as
      documentation. The length of the prolonged nerve stump was 13 mm in each case.
      After adding to this value the length of the trunk, i.e. the portion between
      stylomastoid foramen and pes anserinus, the fragments of rerouted nerve were
      elongated up to 21 mm. This distance allowed for performing the facial-hypoglosal
      anastomosis using only one neuroraphy without increased tension.

PMID- 12053667
TI  - [Epstein-Barr virus antibodies in blood serum of patients with laryngeal cancer].
AB  - Association of Epstein-Barr virus with cancers of upper respiratory tract has
      been recently reported. The aim of our study was to determine the prevalence of
      serum IgG and IgM antibodies against Epstein-Barr virus capsid antigen (EBVCA)
      and nuclear antigen (EBNA) in patients with laryngeal cancer. Serum samples from
      28 patients with laryngeal cancer were evaluated for presence of IgG and IgM
      EBVCA and EBNA antibodies using ELISA assay. Serum from 18 healthy age and sex
      matched individuals served as control. Patients with laryngeal cancer and healthy
      subjects were negative for anti-EBV-VCA IgM antibodies (< 20 IU). Serum samples
      were positive for IgG EBNA in 85.7% of patients with laryngeal cancer and in
      72.2% of control group. 89.3% of patients with cancer and 88.8% of healthy
      individuals were positive for IgG VCA antibodies. The mean level of IgG EBNA
      (107.8 +/- 71.4) and IgG VCA (124.8 +/- 54.7) antibodies in patients with
      laryngeal cancer was higher than in control group. The differences were not
      significant. Patients with N0 neck had significantly higher IgG VCA and EBNA
      antibodies levels than patients with N1-N3 neck. The results may suggest a role
      of Epstein-Barr virus in laryngeal cancer pathogenesis.

PMID- 12053668
TI  - [Relationship between inflammation of upper and lower respiratory airways].
AB  - Dysfunction of the upper and lower airways frequently coexists, and they appear
      to share key elements of pathogenesis. Data from epidemiologic studies indicate
      that nasal symptoms are experienced by as many as 78% of patients with asthma and
      that asthma is experienced by as many as 38% of patients with allergic rhinitis.
      Among patients with nasal polyps 27-51% have asthma. Polyps of nasal mucosa
      usually exacerbates symptoms of concomitant asthma. Studies also have identified
      a temporal relation between the onset of rhinitis and asthma, with rhinitis
      frequently preceding the development of asthma. Patients with allergic rhinitis
      and no clinical evidence of asthma commonly exhibit nonspecific bronchial
      hyperresponsivenes. The mechanisms upper and lower airway dysfunction are under
      investigation. They include nasal-bronchial reflex, mouth breathing caused by
      nasal obstruction, and pulmonary aspiration of nasal contents. Nasal allergen
      challenge results in increases in lower airway reactivity within 30 minutes,
      suggesting a neural reflex. Improvements in asthma associated with increased
      nasal breathing may be the result of superior humidification, warming of inspired
      air, and decreased inhalation of airborne allergens. Postnasal drainage of
      inflammatory cells during sleep also may affect lower airway responsiveness. The
      effective management of allergic rhinitis relieves symptoms of asthma. A link
      between allergic rhinitis and asthma is evident from epidemiologic,
      pathophysiologic, and clinical studies. The development of differential diagnosis
      of rhinitis has multiplied their present classifications. This article presents
      classifications of rhinitis connected with lower airways dysfunction.

PMID- 12053670
TI  - [Hyperinsulinemia in vertigo, tinnitus and hearing loss].
AB  - 48 patients (25 woman, mean age 42 +/- 9.9 years and 23 men, mean age 46.6 +/-
      8.3 years) suffering from vertigo, tinnitus and hearing loss of unknown origin
      were included into this study. The occurrence and coexistence of symptoms was
      measured. Insulin levels were measured fasting and at the second hour of OGTT.
      Results were compared with the control group of 31 healthy persons (16 women,
      mean age 41.3 +/- 5.6 years and 15 men, mean age 47.6 +/- 9.4 years). The
      character of vertigo, localization of hearing loss and electronystagmographic
      findings showed the pathology of the inner ear. The occurrence of
      hyperinsulinemia was significantly more common in the patients group--43.8%,
      comparing to the control group--22.6%. Also the insulin levels in the second hour
      of OGTT, were statistically significantly higher in patients that in the control
      group.

PMID- 12053669
TI  - [The value of exploratory anterior tympanotomy in differentiating causes of
      conductive hearing loss and assessment of their treatment results].
AB  - The aim of examination was value of exploratory anterior tympanotomy in
      differentiation causes of conductives hearing loss and assessment of results
      treatment. Materials of examinations determined 34 patients aged 15-66 years,
      treated in 1995-2000 years, who qualified to exploratory anterior tympanotomy in
      aim decision of cause of conductives hearing loss. Among of examined were 14
      patients with suspicion of otosclerosis (41.2%), 12 patients with unclear
      etiology of hypoacusis (35.3) and 8 patients with deterioration of hearing after
      stapedectomy (23.5%). Preoperative diagnostic embraced: a history,
      otolaryngologic examination, full audiologic examination and chosen cases of
      radiologic assessment of temporal bone by computer tomography. After
      perioperative decision cause of conductive hypoacousis were performed of
      operations of improved hearing and comprised of average hearing loss by CPT and
      PTA pre- and postoperative treatment. After performed of exploratory tympanotomy
      there vere stated following causes of conductive hypoacusis: otosclerosis
      (61.8%), separated of prosthesis after stapedectomy (14.7%) synechia of
      prosthesis with tympanic membrane (8.8%) and in singles causes of ossicular
      synechia in tympanic cavum (5.9%), tympanosclerosis (5.9%) and vitium of middle
      ear (2.9%). The best of hearing improvement after repairment operations of
      conductive system were obtained in cases of stapedectomy, exchange of prosthesis
      after stapedectomy, reconstruction of system by TORP prosthesis, however smaller
      improvement after operations of synechias of stapes prosthesis with surroundings
      and postoperation of tympanosclerosis.

PMID- 12053671
TI  - [Surgical treatment of acquired external auditory canal atresia].
AB  - Acquired atresia of the external auditory canal is a relatively rare disease,
      that can be the result of the recurrent external otitis, chronic media otitis,
      ear trauma, neoplasms or iatrogenic complications. The surgical treatment results
      after operation in the 7 patients with acquired external auditory canal atresia
      were presented. The mean age of the patients was 34.1 and the female to male
      ratio was 2:5. In 6 cases we performed transcanal operation. The meatus atresia
      was removed and then the stenotic canal was widened by removing the skin and
      fibrous tissue. We especially focused our attention on the state of the anterior
      angle of the tympanic membrane. The bony canal was widened by burr in cases with
      bony overhangs. The bony canal walls were lined with pediculate or free skin
      grafts. In cases of tympanic membrane perforation we performed myringoplasty with
      temporal muscle fascia or tragus perichondrium. The follow-up period was from 8
      to 39 months. The hearing improvement with primary closure of air bone gap within
      20 dB was achieved in 43% of cases. In 28% of the patients recurrent atresia
      developed. The early surgical treatment is recommended in all the cases because
      cholesteatoma behind the atresia was found in 28% of patients.

PMID- 12053672
TI  - [Acoustic evaluation of voice in children with cleft palate].
AB  - The study presents some problems related to objective methods of evaluation of
      nasalization due to a cleft palate. A group of 30 children 3-11 years old were
      referred for evaluation of nasalization through acoustics. The primary factor of
      children speech disability with cleft palate is velopharyngeal valving
      malfunction which results in hypernasal voice quality. The hypernasality is one
      of the most important features of cleft palate speech and its objective
      evaluation after surgical operation is recommended to assessment of
      velopharyngeal insufficiency and therapy efficiency prognosis. Some problems in
      clinical application of acoustical methods of speech nasality evaluation are
      discussed.

PMID- 12053673
TI  - [Effect of middle ear impedance on hearing threshold level in children with
      adenoid hypertrophy].
AB  - The adenoid hypertrophy in children may lift the hearing threshold level
      especially for low frequency and also influence on the middle-ear impedance. The
      authors tested eighteen children with adenoid hypertrophy and ten healthy
      children. The tone audiometry for 250 Hz-8 kHz and impedance audiometry was made.
      For eight children with adenoid hypertrophy tests were made before and after
      adenoidectomy (surgical removal of the adenoids). The authors found the relation
      between the curve of the hearing threshold level and the middle-ear impedance. It
      was found correlation between the middle-ear impedance and the value of hearing
      threshold level for 250 Hz, 1000 Hz, 2000 Hz and average of value for 250, 500
      and 1000 Hz. There was no correlation between the middle-ear impedance and the
      value of hearing threshold level for 500 Hz and average of value for 500, 1000
      and 2000 Hz.

PMID- 12053674
TI  - [Results of combined treatment for vestibular receptor impairment with physical
      therapy and Ginkgo biloba extract (Egb 761)].
AB  - Vestibular receptor impairment causes symptoms called vestibular organ peripheral
      lesion syndrome. Subjective and objective symptoms of vestibular lesion diminish
      gradually in the process of vestibular compensation. Stimulating a patient to
      action is a basic factor that influences on the compensation process. The aim of
      our studies was an evaluation of treatment results in patients with vertigo of
      peripheral origin with the use of gingko biloba extract together with
      kinezytherapy. Ginkgo biloba extract shows vasoactive, rheologic, metabolic and
      neural effects. We have examined 45 persons aged between 35 and 48 years (38 on
      average, 35 female, 13 male) with clinical symptoms of peripheral vestibular
      lesion. In each case we performed as follows: ORL physical examination, pure tone
      audiometry, suprathreshold audiometry, electronystagmography (eyes open and
      closed nystagmus, cervical tests, caloric tests according to Hallpike), static
      and dynamic posturography. In all of the cases vestibular rehabilitation
      originally programmed in our Clinic was applied. N 23 cases (17 female and 6
      male) chosen at random, kinezytherapy together with gingko biloba in tablet was
      applied: 2 tablets twice a day for 3 months. Control examination were performed
      on 30, 60 and 90 days of treatment. Treatment results evaluation was based on
      anamnesis, electronystagmography, static and dynamic posturography. CONCLUSIONS:
      1. In almost all of the cases with peripheral lesion of vestibular organ, after
      30 days of application of gingko biloba extract together with kinezytherapy and
      without gingko biloba there was vestibular compensation confirmed in
      electronystagmography but there were disturbances in static and dynamic
      posturography. 2. Control examination in the course of treatment revealed gradual
      improvement in vestibular tests in both group (with and without biloba extract).
      But in patients treated with gingko biloba extract the improvement was more clear
      and faster an dynamic posturography. It implies central effect of gingko biloba
      extract that allows to gain full vestibular compensation sooner.

PMID- 12053675
TI  - [Multiple primary neoplasms on the face].
AB  - A case of 74-year old woman with six separate cancers is presented. Four of them
      were nonmelanoma skin cancers (2 basal-cell carcinomas and 2 squamous-cell
      carcinomas), the remaining two were noncutaneous malignancies (invasive lobular
      carcinoma of the breast and squamous cell carcinoma of the parotid gland). Three
      lesions were present simultaneously on the head and neck region; basal-cell
      carcinoma on the cheek, squamous-cell carcinomas on the forehead, and in the
      parotid gland. All neoplasms were surgically removed, the region of affected
      parotid gland was additionally radiated. Extreme rarity of the multifocal primary
      malignancies is emphasized and the non-completely clear etiology, biology and
      pathology of these tumors is discussed.

PMID- 12053676
TI  - [Acute invasive fungal rhinosinusitis--case report].
AB  - A case report of acute invasive fungal rhinosinusitis in 28 year old woman with
      acute myeloid leukemia is described in this paper. The diagnosis of the fungal
      disease was based on clinical presentation, endoscopic evaluation of nasal
      cavity, computed tomography and magnetic resonance imaging of the paranasal
      sinuses and histopathological findings. An aggressive treatment including
      antifungal therapy (amphotericin B), antibiotics and the surgery of paranasal
      sinuses was implemented. Unfortunately the underlying disease and the fungal
      invasion progressed rapidly and the patient died on the forth week post-op due to
      cardiorespiratory failure.

PMID- 12053677
TI  - Predictors of clinical outcome following NIR stent implantation for coronary
      artery disease: analysis of the results of the First International New
      Intravascular Rigid-Flex Endovascular Stent Study (FINESS trial).
AB  - BACKGROUND: Patient and procedural characteristics associated with major adverse
      cardiac events following balloon angioplasty have been identified. Factors
      predictive of angiographic restenosis following coronary stent implantation have
      been reported, although patient variables associated with adverse clinical
      outcome are not well defined. HYPOTHESIS AND METHODS: To identify predictors of
      adverse clinical outcome following NIR stent implantation, clinical and
      angiographic characteristics of patients enrolled in the FINESS Trial were
      subjected to stepwise logistic regression analysis. From December 1995 through
      March 1996, NIR stent implantation was attempted in 255 patients (341 lesions)
      enrolled prospectively in a multicenter registry with broad entry criteria.
      RESULTS: On stepwise logistic regression analysis, the presence of multivessel
      disease, diabetes, and the total length of the stented segment were predictive of
      major adverse cardiac events during 6-month follow-up. For every 1 mm increase in
      stent length, the risk for the combined end point of death or myocardial
      infarction increased by 3%. Lesion length was not predictive of clinical events
      on multivariate analysis. CONCLUSIONS: Our data raise the possibility that an
      attempt to use shorter stents to cover significant stenoses, but not adjacent
      areas of visible narrowing, may improve outcome.

PMID- 12053678
TI  - Exposure of the operator to ionizing radiation during intracoronary radiation
      therapy.
AB  - This study examined the radiation exposure levels and safety of medical personnel
      during intracoronary radiotherapy procedures. The data of 34 stenosis patients
      from a total of 42 irradiated patients who participated in the Seoul National
      University Hospital Postangioplasty Rhenium (SPARE) trial were analyzed.
      Intracoronary radiotherapy was delivered to the patient immediately after
      angioplasty ballooning. The prescribed dose was 17 Gy to the media of the
      diseased artery and was delivered via a Re-188 filled balloon catheter. Dosimetry
      was carried out with a Geiger-Muller counter at eight different points. The
      selected maximum and whole-body exposed doses to the operator were 10 cm and 40
      cm from the patient's heart. Median delivered activity was 111.6 MCi, with an
      average treatment time of 576 seconds. Average exposed dose rates at 10 cm and 40
      cm from the patient's heart level were 47.2 mrem/hour and 29.6 mrem/hour,
      respectively, and average exposed doses per treatment were 7.0 mrem and 4.9 mrem,
      respectively. Exposure levels measured were much lower than the recommended limit
      of 50 mSv for radiation workers or 1 mSv for the general population, as
      recommended by the International Commission on Radiological Protection. This
      study proves that the method of intracoronary radiotherapy currently adopted and
      which is the basis of this trial is safe with respect to radiation protection.

PMID- 12053679
TI  - Acute cardiogenic shock immediately after successful intervention for failed
      thrombolysis.
AB  - We report the case of a 60-year-old female with a history of hypertension who was
      admitted with an acute inferior myocardial infarction. She received rescue
      percutaneous transluminal coronary angioplasty/stenting of an occluded right
      coronary artery for failed thrombolysis with a good initial result. However, this
      was immediately complicated by cardiogenic shock characterized by left
      ventricular outflow tract (LVOT) gradient. She was treated with intravenous
      fluids and adrenaline. Predischarge echocardiography showed no LVOT gradient and
      features of left ventricular hypertrophy that mainly affected the septum.

PMID- 12053680
TI  - Fractional flow reserve in a patient with intermediate coronary stenosis and
      hypertrophic cardiomyopathy.
AB  - We discuss the case of a 61-year-old male patient with hypertrophic
      cardiomyopathy and chest pain on exertion. Coronary angiography and intravascular
      ultrasound revealed an intermediate stenosis in the proximal site of the left
      anterior descending artery, while Tc-99m myocardial scintigraphy revealed
      exercise-induced myocardial ischemia in the anteroseptal wall and apical portion.
      Flow velocity-derived coronary flow reserve (CFR) and pressure-derived fractional
      flow reserve (FFRmyo) were both low (1.1 and 0.59), suggesting that the stenosis
      was functionally significant. Directional coronary atherectomy greatly improved
      the FFRmyo (0.99), the scintigraphic findings, and anginal pain but did not
      improve the CFR (1.2). FFRmyo was useful in assessing the functional significance
      of an equivocal coronary stenosis and its interventional resolution.

PMID- 12053681
TI  - Stent placement for coronary stenosis in Kawasaki disease: case report and
      literature review.
AB  - A 48-year-old male patient diagnosed with Kawasaki disease in childhood presented
      with recurrent angina after undergoing coronary artery bypass surgery in 1996.
      Percutaneous transluminal coronary angioplasty and intracoronary stent placement
      to a lesion in the proximal ramus intermedius were performed successfully. This
      case illustrates the complementary nature of percutaneous and surgical myocardial
      revascularization strategies in appropriately selected patients with Kawasaki
      disease.

PMID- 12053682
TI  - Evolution of interventional cardiology in Germany.

PMID- 12053683
TI  - Antiplatelet therapy and coronary interventions: childhood friends or permanent
      partners?

PMID- 12053684
TI  - The pharmacodynamics of parenteral glycoprotein IIb/IIIa inhibitors.
AB  - Glycoprotein (GP) IIb/IIIa antagonists are a unique class of antiplatelet agents
      introduced for the management of patients undergoing percutaneous coronary
      intervention (PCI) and those presenting with unstable angina or non-ST segment
      elevation (NSTE) myocardial infarction (MI), collectively recognized as acute
      coronary syndromes (ACS). Eptifibatide, abciximab, and tirofiban HCl are three
      GPIIb/IIIa antagonists approved for use by the Food and Drug Administration. Of
      the three agents, eptifibatide is approved for use in both PCI and NSTE ACS
      patient populations, whereas abciximab is indicated for patients undergoing PCI,
      and tirofiban is approved for patients with NSTE ACS. Dose selection for the
      initial trials using the three parenteral antagonists was based on in vitro and
      ex vivo pharmacodynamic assays conducted under different blood collection and
      platelet function assay conditions. Recent comparative pharmacodynamics studies,
      which used newly defined and standardized assay conditions, indicate that the
      platelet aggregation inhibition achieved with these dosing regimens is variable.
      Therefore, the differences in clinical efficacy as evidenced in the more recent
      clinical studies (e.g., Enhanced Suppression of the Platelet Receptor GPIIb/IIIa
      using Integrilin Therapy [ESPRIT], Global Use of Strategies to Open Occluded
      Coronary Arteries IV Acute Coronary Syndromes [GUSTO-IV ACS], and Do Tirofiban
      HCl and ReoPro Give Similar Efficacy Outcomes Trial [TARGET]) may be related to
      the variable antiplatelet effects of the approved dose regimens.

PMID- 12053685
TI  - Monitoring of platelet function in the setting of glycoprotein IIb/IIIa inhibitor
      therapy.
AB  - The role of the platelet in the pathogenesis of acute coronary syndromes is
      clearly established. In addition, the beneficial effects of oral and intravenous
      platelet inhibitor therapies were demonstrated in multiple, large, randomized
      clinical trials. However, despite these advances, current antiplatelet therapy
      fails to prevent coronary events in a substantial proportion of patients. One
      possible explanation for this phenomenon is that antiplatelet medications are
      administered without monitoring of the response to therapy. For example, oral
      antiplatelet therapy is administered as a standard dose for all patients, while
      intravenous inhibitors of the platelet glycoprotein (GP) IIb/IIIa receptor are
      dosed based on patient body weight. A major limitation of measuring platelet
      function has been that no practical test exists. The historic gold standard,
      bleeding time, was a very crude measure of platelet function with limited
      clinical utility. The current "gold standard," turbidimetric aggregometery,
      requires a central laboratory and is cumbersome to perform. Fortunately, a number
      of new tests with rapid turnaround time can be performed at the patient's
      bedside. This article discusses the details regarding the performance,
      advantages, disadvantages, and available data related to clinical use of each
      test in populations with coronary disease and patients treated with antiplatelet
      therapy.

PMID- 12053686
TI  - Catheter-based transendocardial myocardial gene transfer.
AB  - BACKGROUND AND AIM: Local modulation of myocardial function by gene transfer or
      cell depositions constitutes a potential method of cardiac treatment. This study
      tested the morphology of myocardial plasmid gene transfer by catheter-based
      transendocardial injection (NOGA). METHODS: Left ventricular morphology and
      electrical and mechanical characteristics were mapped in three dimensions. In two
      pigs, 0.10 mL of toluidine blue was injected at ten sites. In seven pigs, seven
      to ten injections of 0.10 mL saline containing 0.10 mg pCMV-LacZ expressing the
      enzyme beta-galactosidase and 0.10 mg phVEGF-A165 were given. The pigs were
      sacrificed after 3 days and gene expression was determined. RESULTS:
      Macroscopically on the endocardial surface, all identified spots were located in
      the target area. However, along the transmyocardial axis, injections with color
      and plasmid were located randomly throughout the left ventricular wall from the
      endocardium to the epicardium. In each detected spot, gene expression of beta
      galactosidase was observed in an approximate myocardial volume of 5 x 5 x 5 mm.
      Microscopically, the transfected cells were located typically at the tip of the
      injection scar. As a rule, 10 to 20 transfected cells were located at the end of
      the injection scar. In sections where expression of both transcripts was
      observed, 42% of the cells expressed both beta-galactosidase and vascular
      endothelial growth factors (VEGF), 32% only beta-galactosidase, and 26% only
      VEGF. CONCLUSIONS: Myocardial gene transfer following magnetic guidance can be
      located precisely on the left ventricular inner surface. Within the myocardium,
      gene expression is local around the distal tip of the injection scar and is
      located randomly at every level of depth of the left ventricular wall.

PMID- 12053687
TI  - The use of the glycoprotein IIb/IIIa receptor antagonists during percutaneous
      coronary intervention.
AB  - Coronary thrombosis is the major cause of ischemic complications during
      percutaneous coronary interventions (PCI). The glycoprotein (GP) IIb/IIIa
      receptor plays a critical role in the process of platelet thrombus formation
      since it serves as the final common pathway for platelet aggregation. Presently,
      there are three commercially available intravenous GPIIb/IIIa inhibitors that
      block fibrinogen binding to its receptor. These agents significantly reduce the
      incidence of death and nonfatal myocardial infarction at 30 days in patients
      undergoing percutaneous coronary revascularization. In addition, the early
      benefits appear to be sustained at 6 months to 1 year. Increasing evidence shows
      that the predominant mechanism of benefit is due to a reduction in embolization
      to the microcirculation that occurs during PCI. While data regarding the
      comparative efficacy and cost-effectiveness of these agents are scarce, the
      magnitude of benefit appears to be greatest for abciximab. Furthermore, a
      mortality benefit has been demonstrated only for abciximab. Although high risk
      patients reap the greatest benefit from the use of these agents, it is clear that
      even patients who are classified as low-to-moderate risk still derive substantial
      benefit from their use. Finally, evidence indicates that the majority of patients
      with acute coronary syndromes without ST segment elevation who are scheduled to
      undergo PCI should be pretreated with a GPIIb/IIIa receptor antagonist.

PMID- 12053688
TI  - The thienopyridines.
AB  - Platelet adhesion, activation, and aggregation are key processes in the
      pathogenesis of coronary disease. Inhibition of these processes forms the
      cornerstone of therapy for coronary artery disease and particularly of acute
      coronary syndromes (ACS). Aspirin was the only available antiplatelet therapy for
      over 100 years, and it improves clinical outcome in a wide range of clinical
      situations. However, aspirin only inhibits platelet activation mediated by
      thromboxane A2, allowing platelet activation to occur through innumerable other
      pathways. As a result, adverse ischemic events are common when aspirin alone is
      used for the treatment of coronary disease, including ACS, during coronary
      interventions (particularly during stent implantation), and following coronary
      vascular brachytherapy (VBT). In these clinical situations, the presence of
      either thrombus, deep injury to the vessel wall, or delayed vascular
      reendothelialization leads to intense and often prolonged platelet activation,
      overwhelming the relatively weak effects of aspirin. The development of the
      thienopyridines, a class of antiplatelet drugs that reduce adenosine diphosphate
      (ADP) mediated platelet activation, has significantly improved clinical outcomes
      in many coronary conditions. Widespread use of ticlopidine, the first available
      thienopyridine, was limited by frequent side-effects, including life-threatening
      neutropenia and thrombotic thrombocytopenic purpura. Following the introduction
      of clopidogrel, a thienopyridine with an excellent safety profile, dual
      antiplatelet therapy with aspirin and clopidogrel has become standard therapy
      following coronary stent implantation and coronary VBT. In patients presenting
      with ACS, the addition of clopidogrel to aspirin has now been proven to reduce
      ischemic events. The most important limitation of dual antiplatelet therapy is
      the increased bleeding risk as compared with aspirin alone, particularly in
      patients undergoing coronary artery bypass grafting during the index
      hospitalization. However, for many patients with ACS, combination therapy is
      appropriate.

PMID- 12053689
TI  - [Current status of dermatomicrobiology. An overview].
AB  - The new German laws dealing with protection against infectious diseases
      (Infektionsschutzgesetz of 1.1.2001) have reconfirmed the importance of
      microbiology as a basic science and infectiology as a multi-disciplinary clinical
      discipline. Concerning dermatological diagnosis and therapy, the implementation
      of molecular biological techniques has a decisive influence. The discovery of new
      (e.g. Helicobacter pylori) and the better detection of known organisms (e.g.
      Chlamydia, Borrelia) suggested findings in questions of causality and therapeutic
      developments. Concerning the infections of the skin this synopsis provides the
      state of the art of diagnostic process and treatment in mycology, bacteriology
      and virology.

PMID- 12053690
TI  - [Gene therapy concepts for promoting wound healing].
AB  - Growth factors are important players in orchestrating all stages of wound
      healing. They are mitogen, chemotactic, they regulate cell-cell interactions and
      influence synthesis and composition of extra-cellular matrix components. The use
      of growth factors to stimulate wound healing is a promising new therapeutic
      approach to repair chronic tissue defects. The delivery of genetic material
      offers an attractive treatment modality to produce an appropriate amount of
      growth factor proteins within the wound site. This review discusses several
      methods of growth factor gene transfer into wound tissue and presents recent
      experimental results of gene therapy approaches in stimulating wound repair.

PMID- 12053691
TI  - [In vivo differentiation of pigmented skin tumors with laser Doppler perfusion
      imaging].
AB  - BACKGROUND AND OBJECTIVE: Malignant melanomas show a higher heterogeneity in
      their architecture and a higher vessel density because of neovascularization
      compared to benign melanocytic skin tumours. In this study the validity of the
      newly developed Laser Doppler Perfusion Imager (LDPI) with a lateral resolution
      of 100 microns in the differential diagnosis of pigmented skin tumours was
      investigated. PATIENTS/METHODS: The perfusion of 116 pigmented skin tumours was s
      measured with LDPI; 44 malignant melanomas, five melanoma metastases, 59
      dysplastic nevi and eight basal cell carcinomas were studied before excision for
      precise histological diagnosis. RESULTS: There is a significantly higher
      perfusion of the malignant melanomas (3.15 +/- 1.87 AU) compared to dysplastic
      nevi (1.14 +/- 0.97 AU) (p < 0.01). By calculating a ratio of the mean perfusion
      in the tumour and the mean perfusion in adjacent healthy skin, the potential
      source of error because of regional differences in perfusion is eliminated. The
      ratio of malignant melanomas (10.78 +/- 9.18) is significantly higher than these
      of melanoma metastases (4.20 +/- 1.66), basal cell carcinomas (3.24 +/- 1.32) and
      dysplastic nevi (2.85 +/- 1.32). CONCLUSIONS: The high resolution LDPI has the
      potential to be a non-invasive screening method for preoperative differential
      diagnosis of pigmented skin tumours. Besides the epiluminescence microscopy and
      sonographic determination of the tumour thickness, we have now the possibility to
      get preoperative information about tumour vascularization.

PMID- 12053692
TI  - [Melanoma on congenital nevus. Malignant differentiation after radiotherapy?].
AB  - Giant congenital nevi involve an approximately 5% risk of malignant
      transformation. We report about a 27-year-old patient who developed malignant
      melanoma after radiation of a large congenital nevus of the foot which was
      initially misinterpreted as a trophic disorder. The mechanisms and probability of
      malignant transformation and prophylactic therapy of large vs small congenital
      nevi are discussed.

PMID- 12053694
TI  - [Scrotal leiomyoma].
AB  - Genital leiomyomas of the scrotal skin are extremely rare benign tumors,
      originating from the tunica dartos of the scrotum. We describe a 55-year-old
      caucasian male with a 3-year history of a slowly growing asymptomatic scrotal
      knot which was first clinically regarded as a cyst and finally diagnosed
      histopathologically as leiomyoma. This typical case demonstrates that leiomyomas
      should be considered in the differential diagnosis of scrotal tumors.

PMID- 12053693
TI  - [Skin manifestations of Fanconi anemia].
AB  - Fanconi's anemia is a rare autosomal recessive disorder associated with variable
      clinical manifestations. So far, eight complementation groups have been
      identified, and the genes of four of them have been cloned. Early-onset
      progressive bone marrow failure and a predisposition to malignancies,
      particularly acute myelogenous leukemia, liver tumors, and mucocutaneous squamous
      cell carcinomas, result in a poor prognosis. Additionally, almost all organs can
      be affected by this defect. Widespread areas of hyper- and hypopigmentation of
      the skin in a characteristic pattern and cafe-au-lait spots preceding the
      manifestation of panmyelopathy can aid early diagnosis. Here we report an 11-year
      old boy with Fanconi's anemia presenting with typical cutaneous manifestations.
      We emphasize the important role of skin abnormalities of Fanconi's anemia as
      signs enabling early diagnosis. Moreover, we summarize clinical features, course,
      therapy, and new aspects of the molecular basis of Fanconi's anemia.

PMID- 12053695
TI  - [Giant cavernous hemangioma of the scalp].
AB  - Cavernous hemangiomas of the scalp associated with vascular tumors of the skull
      occur rarely in older patients. Giant hemangiomas can cause complications
      secondary to extensive bleeding. Here we report on a 78-year-old female
      presenting with a giant ulcerated cavernous hemangioma of the scalp. Before
      admission to the hospital, she had suffered from severe bleeding of the vascular
      tumor, with resulting anemia. Because of her cardiovascular disease, the tumor
      mass, and possible vascular connections to osseous hemangiomas, complete surgical
      removal of the hemangioma was not indicated. Therefore the superficial ulceration
      was covered with a split skin transplant. After complete wound healing, no
      further bleeding occurred.

PMID- 12053697
TI  - [Staging of scientific facts in syphilis education. "The Shipwrecked" in the
      Berlin German Theater (1913)].
AB  - The "Deutsche Gesellschaft zur Bekampfung der Geschlechtskrankheiten" (DGBG) used
      plays as a means of public education. The play "Damaged Goods" (Les Avaries) by
      the French dramatist Eugene Brieux (1858-1932) was used extensively for this
      purpose in Germany between 1910 and 1920. By proliferating a specific image of
      both the medical profession and the syphilis, it helped established the self
      confidence of the then new dermatological discipline. The teaching of Alfred
      Fournier (1832-1914) provided the medical background for the play. In "The
      Inheritance of Syphilis" (1882) Fournier had laid the dramatic framework for
      Brieux' play. Analyzing the Berlin premiere of "Damaged Goods" on June 25 1913 in
      the German Theatre/Berlin, the interplay between scientific facts and theatrical
      license and their diverse influences on the public becomes obvious.

PMID- 12053696
TI  - [Persistent hemorrhagic crusts on the lips of a 13-year-old patient. Cheilitis
      crustosa factitia].

PMID- 12053700
TI  - [Added information and corrections on the continuing education section "Indoor
      allergens"].

PMID- 12053698
TI  - [Bullous autoimmune dermatoses. 2: Pathogenesis].

PMID- 12053699
TI  - [Comment on the contribution by A. Hauschild et al.: "Safety margins in excision
      of primary malignant melanoma"].

PMID- 12053701
TI  - [Recent therapeutic progress in alopecia and hypertrichosis].

PMID- 12053702
TI  - The many roles of oxalate in nature.

PMID- 12053703
TI  - Partners HealthCare: an exercise in marital counseling.
AB  - The high cost of health care in Boston led industry and government to expand
      managed care. The expensive academic health centers had the choice of closing,
      downsizing, merging, and/or integrating. The MGH and BWH chose to develop
      Partners HealthCare (PHCS) an integrated healthcare system that maintained the
      identities of the founding institutions. PHS founded in 1994 is physician-led and
      protects the missions of patient care, research and education. It includes the
      MGH and BWH, four community hospitals and one thousand primary care physicians.
      All administrative services have been consolidated as had several clinical
      departments, residencies and fellowships. Research coordination has resulted in
      shared space, grants, industrial partnerships, and a growth in support. Clinical
      service volumes have surpassed pre-merger levels. Contracts now cover the true
      costs of care and produce positive operating margins and bottom lines. The
      strategy of forming an integrated health system has achieved most but not all of
      its goals.

PMID- 12053704
TI  - The Institute of Medicine and its quality of healthcare in America reports.
AB  - The Institute of Medicine was founded in 1970 under the charter of the National
      Academy of Sciences to address the concerns of medicine and healthcare. Many
      members of the Institute and at least two of its former presidents are also
      members of the Association. For those unfamiliar with the Institute's history and
      purpose, I will provide a brief overview. The National Academy of Sciences was
      chartered in 1863 by President Lincoln and the U.S. Congress, to advise the
      government on scientific issues and technology. As the scope of its activities
      broadened, the Academy established the National Research Council to provide an
      operating entity and staff for the many issues studied by members of the Academy
      and other volunteers. The closely related National Academy of Engineering was
      created in the 1960's and it also utilized the staff and facilities of the
      National Research Council. During the 1960's there was increasing need and
      concern for the establishment of an entity closely affiliated with the National
      Academy of Sciences that could provide advice, counsel, and studies on difficult
      issues in medicine and in the social, economic, and political aspects of
      healthcare. The Institute of Medicine evolved from these deliberations and, like
      the National Academy of Sciences, is an independent, non-governmental, nonprofit
      organization with a mandate to provide the government and others with advice,
      counsel, and independent research on major topics in healthcare.

PMID- 12053705
TI  - Clinical research in the private office setting--ethical issues.
AB  - A new model for performing clinical investigations has emerged in the United
      States which utilizes networks of physicians practicing in private office
      settings. This arrangement has sparked much controversy because of the potential
      conflicts of interest inherent in the dual roles of physician as clinician and
      investigator as well as the significant direct financial gains reported by some
      physicians which might impact on the interests of research subjects. We describe
      some of the ethical concerns and propose some procedural guidelines to safeguard
      the interests of research subjects participating in clinical trials in private
      physician offices. These safeguards include: requiring education of all
      investigators in research ethics, limiting financial incentives, disclosure to
      subjects of potential conflicts and financial arrangements, creation of an
      independent resource available to subjects to discuss concerns and answer
      questions, and development of educational materials to inform all potential
      subjects about important issues related to clinical research.

PMID- 12053706
TI  - Clinical examination: still a tool for our times?
AB  - Physical diagnosis, as an integral part of the diagnostic process and as a
      central component of the physician-patient relationship, is at a crossroad.
      Technology offers a more sophisticated and, in many instances, more accurate
      solution to diagnostic problems, while evidence mounts suggesting that students'
      and residents' physical diagnosis skills are inadequate. For several reasons,
      however, physical diagnosis must remain a core skill for clinicians, particularly
      for those who practice in outpatient settings. Recent literature critically
      appraising specific physical diagnosis maneuvers has identified the components of
      physical exam that are well worth learning and using, as well as the specific
      clinical conditions in which physical exam can and should play a central
      diagnostic role. Interestingly, critical appraisal of physical diagnosis also
      underscores the importance of proper technique. Thus, physical examination now
      can be approached as a science, based upon sound evidence, and as an art as well.

PMID- 12053708
TI  - Theodore E. Woodward Award. How bacterial enterotoxins work: insights from in
      vivo studies.
AB  - Clostridium difficile is a spore forming, gram-positive anaerobic bacillus first
      described in 1935 by Hall and O'Toole as a commensal organism in the fecal flora
      of healthy newborn infants (1). The organism was given its unusual name because
      it grew slowly and was difficult to isolate in pure culture. Its presence in the
      stool of healthy neonates suggested that C. difficile was a nonpathogen, even
      though it produced toxins in broth culture. Following its original description,
      C. difficile passed quickly into relative obscurity in the 1960's and 1970's when
      antibiotic-associated pseudomembranous colitis became prevalent following the
      introduction into clinical practice of broad spectrum antibiotics. The frequent
      association of clindamycin and lincomycin therapy with pseudomembranous colitis
      led to the term "clindamycin colitis" (2). A breakthrough occurred in 1978 when
      C. difficile was identified as the source of a cytotoxin in the stool of patients
      with pseudomembranous colitis (3). During the two decades since its rediscovery,
      a great deal has been learned about the pathophysiology, epidemiology and
      management of C. difficile infection, yet many challenges remain. Currently this
      organism infects over 30% of individuals admitted to United States hospitals,
      making C. difficile colitis one of the most common nosocomial infections (4). It
      is estimated that approximately 10-12 million adults are infected with this
      organism each year in the United States, about a third of whom become
      symptomatic. The disease burden in the elderly is particularly severe as they are
      hospitalized more frequently and for longer duration. The pathophysiology of C.
      difficile diarrhea requires alteration of the colonic microflora by antibiotics,
      colonization by C. difficile, and release of two potent enterotoxins designated A
      and B (5). The toxins of Clostridium difficile are required virulence factors in
      both animals and humans since non-toxigenic strains do not cause disease. Recent
      cloning and sequencing of the toxin genes reveals extensive amino acid homology
      between them that is reflected in common molecular and cellular mechanisms. Both
      toxins damage cells by modifying the rho family of proteins, key regulators of
      cellular actin. C. difficile infection causes a florid acute inflammatory
      response seen in patients with pseudomembranous colitis. It is now realized that
      neurons and immune cells of the lamina propria are major determinants of toxin
      induced diarrhea and mucosal damage. Early critical events following toxin
      exposure are release of the neuropeptides substance P and calcitonin gene related
      peptide (CGRP) from sensory afferent neurons and activation of lamina propria
      macrophages and intestinal mast cells. These peptides in turn release a complex
      cascade of other inflammatory mediators from lamina propria cells (5). The
      importance of the host immune response, specifically serum IgG directed against
      toxin A, is now recognized as a critical determinant of disease expression in
      man.

PMID- 12053707
TI  - Interactions of ethanol and folate deficiency in development of alcoholic liver
      disease in the micropig.
AB  - Folate deficiency is present in most patients with alcoholic liver disease (ALD),
      whereas folate regulates and alcoholism perturbs intrahepatic methionine
      metabolism, and S-adenosyl-methionine prevents the development of experimental
      ALD. Our studies explored the hypothesis that abnormal methionine metabolism is
      exacerbated by folate deficiency and promotes the development of ALD in the
      setting of chronic ethanol exposure. Using the micropig animal model, dietary
      combinations of folate deficiency and a diet containing 40% of kcal as ethanol
      were followed by measurements of hepatic methionine metabolism and indices of
      ALD. Alcoholic liver injury, expressed as steatohepatitis in terminal 14 week
      liver specimens, was evident in micropigs fed the combined ethanol containing and
      folate deficient diet but not in micropigs fed each diet separately.
      Perturbations of methionine metabolism included decreased hepatic S
      adenosylmethionine and glutathione with increased products of DNA and lipid
      oxidation. Thus, the development of ALD is linked to abnormal methionine
      metabolism and is accelerated in the presence of folate deficiency.

PMID- 12053709
TI  - The new stem cell biology.
AB  - Recent studies have indicated that bone marrow stem cells are capable of
      generating muscle, cardiac, hepatic, renal, and bone cells. Purified
      hematopoietic stem cells have generated cardiac and hepatic cells and reversed
      disease manifestations in these tissues. Hematopoietic stem cells also alter
      phenotype with cell cycle transit or circadian phase. During a cytokine
      stimulated cell cycle transit, reversible alterations of differentiation and
      engraftment occur. Primitive hematopoietic stem cells express a wide variety of
      adhesion and cytokine receptors and respond quickly with migration and podia
      extensions on exposure to cytokines. These data suggest an "Open Chromatin" model
      of stem cell regulation in which there is a fluctuating continuum in the stem
      cell/progenitor cell compartments, rather than a hierarchical relationship. These
      observations, along with progress in using low dose treatments and tolerization
      approaches, suggest many new therapeutic strategies involving stem cells and the
      creation of a new medical specialty; stemology.

PMID- 12053710
TI  - Recombinant thyrotropin for detection of recurrent thyroid cancer.
AB  - Detection of recurrent thyroid cancer tumor requires TSH stimulation for
      radioiodine scanning and thyroglobulin (Tg) measurement. Temporary thyroid
      hormone withdrawal has previously been used, but causes hypothyroidism and,
      rarely, tumor progression. METHODS: The alternative of recombinant thyrotropin
      (rTSH) was assessed in two randomized clinical trials in which patients had 131I
      and Tg testing twice: first after rTSH, and second after thyroid hormone
      withdrawal. Test results and quality of life were compared. RESULTS: In the first
      trial, among 62 of 127 patients with positive scans, rTSH was equivalent to
      withdrawal in 41, superior in 3, and inferior in 18 (P < 0.05), suggesting a
      lesser sensitivity of rTSH scans. In a second trial employing enhanced
      techniques, among 108 of 220 patients with positive scans, there was no
      difference in the number of superior rTSH and withdrawal scans. Furthermore,
      among all patients with withdrawal study evidence of residual thyroid tissue, 74%
      of all patients with residual thyroid tissue and 100% of patients with tumor
      metastases had rTSH-stimulated thyroglobulin values above 2 ng/mL. Naturally,
      patients experienced significantly more symptoms and diminished quality of life
      when hypothyroid than after rhTSH. CONCLUSIONS: Combined rTSH-stimulated
      radioiodine and Tg testing is as sensitive as thyroid hormone withdrawal to
      detect recurrent thyroid cancer, and causes less morbidity.

PMID- 12053712
TI  - Academic-industrial collaboration: the good, the bad, and the ugly.
AB  - Academic-industrial collaborations and technology transfer have over the past 50
      years played an increasingly prominent role in the biomedical sciences.
      University partnerships with industry can expedite the availability of innovative
      drugs and other medical technologies, bringing both important public health
      benefits and a source of income for universities and their faculty through a
      variety of financial arrangements. However, these relationships raise ethical
      concerns, particularly when research involves human subjects in clinical trials.
      Lapses in oversight of industry-sponsored clinical trials at universities, and
      especially patient deaths in a number of trials, have brought these issues into
      the public spotlight and have led the federal government to intensify its
      oversight of clinical research. The leadership of Harvard Medical School convened
      a group of leaders in academic medicine to formulate guidelines on individual
      financial conflicts of interest. They and other groups are working to formulate a
      national consensus on this issue.

PMID- 12053713
TI  - Managing patients with papillary thyroid carcinoma: insights gained from the Mayo
      Clinic's experience of treating 2,512 consecutive patients during 1940 through
      2000.
AB  - 2,512 consecutive patients with papillary thyroid carcinoma (PTC) were managed
      during 1940 through 2000 at the Mayo Clinic. During that period, there were two
      significant therapeutic trends. The first was a change in surgical practice
      during 1940-69 from an initial unilateral lobectomy (UL) to a bilateral lobar
      resection (BLR). The second was the increasing use since 1970 of I-131 for
      radioactive-iodine remnant ablation (RRA). The advent of BLR resulted in
      significantly improved tumor recurrence (TR) rates in both low-risk (MACIS scores
      < 6) and high-risk (MACIS scores 6+) patients, and also reduced cause-specific
      mortality (CSM) in high-risk patients. By contrast, RRA did not significantly
      improve the outcome (either CSM or TR) in low-risk (MACIS < 6) patients
      previously treated with initial near-total or total thyroidectomy. These data
      encourage a more selective use of I-131 in PTC management and do not lend support
      to the current widespread use of RRA in low-risk PTC.

PMID- 12053711
TI  - The Jeremiah Metzger Lecture. Polycystic kidney disease: old disease in a new
      context.
AB  - I want to thank the organizers for inviting me to present the Jeremiah Metzger
      Lecture at this, the 114th meeting of the ACCA. It is a high honor, indeed, to
      join a list of very distinguished predecessors. And for this opportunity to tell
      you about my passion in medicine and science, I am most grateful. Most of you in
      this room have passing knowledge of polycystic kidney disease, probably hearing
      about it in your medical school Pathology course where you were shown an
      especially grotesque, enormously enlarged kidney either encased in transparent
      plastic or submerged in a bucket of formaldehyde. In that minute or two when PKD
      was discussed in lecture, you may have been told that this is a rare, hereditary
      disorder that causes kidney failure and that nothing can be done to alter that
      course. Unless you chose to specialize in General Internal Medicine or
      Nephrology, you may not have encountered PKD again until today, despite the fact
      there are approximately 600,000 PKD patients in the USA and over 10,000,000
      worldwide, and it accounts for approximately 5% of non-diabetic dialysis and
      renal transplant patients (Table 1). I might have overlooked PKD as well had it
      not been for a close friend that I grew up with who had inherited the disease
      from his mother. He was very open about the fact that he had cysts in his kidneys
      that caused bleeding into the urine from time to time, especially after a solid
      hit during a game of tackle football. We remained friends long after I left home
      for college and medical school. At an early stage of my research career in
      medicine, while wondering how nephron segments processed glomerular filtrate, I
      inadvertently discovered that renal tubules could secrete as well as reabsorb
      salt and water. This was quite an unexpected finding at the time (1). But it
      occurred to [table: see text] me that this might be a means to fill renal cysts
      with fluid and so I decided to learn more about the pathology and pathogenesis of
      PKD. This didn't take long, because there wasn't much literature on the subject.
      The clinical manifestations of PKD were described in the 19th century European
      medical literature and Sir William Osler had published on the topic in this
      country, but by and large only a few descriptions of small groups of patients
      were reported through the middle of the 20th century. In 1957, Dalgaard (2)
      reported in a classic doctoral thesis that the most common type of hereditary PKD
      is transmitted as an autosomal dominant trait (ADPKD) with complete penetrance.
      It is a bilateral renal condition, but cysts also occur in the liver
      (approximately 60%), pancreas (approximately 10%) and various other organs, and
      it is associated with cerebral aneurysms in approximately 5% of patients. A
      recessive form that affects infants and children primarily (ARPKD), is much rarer
      than ADPKD and commonly leads to death in infancy in association with massively
      enlarged kidneys (Table 2). I was also attracted to the study of PKD because the
      etiology was not in question: it had to be mutated DNA. Yet that fact proved to
      be a hindrance in attaining research support. As some of you will recall, not too
      long ago genetic diseases were viewed by kidney-oriented NIH review panels to be
      incurable. I was advised that a young scientist's time would be better spent
      determining how the kidneys excrete salt and water. Fortunately, the era of
      molecular genetics and biology was upon us, and we quickly learned that uncommon
      genetic disorders could lead to the discovery of novel molecules in metabolic and
      structural pathways. And that is just what happened in the PKD field. The
      autosomal dominant form of PKD led to the discovery of a unique family of highly
      complex proteins long before they would have been selected from a gene or
      proteomic micro-array by some desperate graduate student or fellow. The
      chromosomal location of the major ADPKD genotype, PKD1, was defined in 1985 (3),
      a date that marks the beginning of a remarkable period of discovery.

PMID- 12053714
TI  - The coronary angiogram and its seminal contributions to cardiovascular medicine
      over five decades.
AB  - The selective hand injection of contrast media into the right coronary artery of
      a middle-aged male by Doctor F. Mason Sones on October 30, 1958 introduced a new
      era in Cardiovascular Medicine. It is the purpose of this presentation to portray
      the pivotal role the coronary angiogram has played in creating some of the
      epochal events and discoveries that have characterized the march of progress in
      the field of cardiology over the past five decades. As the first reliable in vivo
      marker for the presence of obstructing coronary lesions, the coronary angiogram
      importantly led to our first studies of the natural history of patients with CAD.
      The motion studies afforded by cineangiography also permitted dynamic
      visualization of the contracting ventricle which led to the concept of regional
      wall motion abnormalities being characteristic of CAD and provided some of our
      earliest understanding of left ventricular dysfunction. The coronary angiogram
      also provided the stimulus for the development of aorto-coronary bypass surgery
      that was introduced by Dr. Rene Favaloro in May 1967. Subsequently, Dr. Andreas
      Gruntzig astounded the cardiology world by reporting his new percutaneous method
      of achieving revascularization (PTCA). The coronary angiogram provided the road
      map necessary for the successful deployment and application of this balloon
      technology that was soon to rival CABG surgery. The thrombolytic era was heralded
      in July 1979 when Dr. Peter Rentrop documented the successful reperfusion of a
      coronary artery in a 57-year old man by first recanalizing the occluding thrombus
      with a guidewire and then infusing the proteolytic enzyme, streptokinase directly
      into the artery. Within a year, DeWood made the angiographic observation that
      spontaneous regression of the totally occluding thrombus occurred among patients
      undergoing coronary arteriography within the first 24 hours of the onset of
      symptoms of an acute myocardial infarction. This led to the earliest studies on
      clot lysis by fibrinolytic agents and also paved the way for the balloon catheter
      to be used as a mechanical means of achieving coronary reperfusion in the acute
      setting. In the 1980s it was realized that vigorous lipid lowering with statin
      drugs did little to effect regression of the established atherosclerotic lesion
      but it did result in a dramatic decrease in subsequent clinical cardiovascular
      events. Similar observations were made by Little and others that acute coronary
      occlusion resulted more often from young, non-obstructing atheromatous lesions
      than it did from high grade obstructive lesions. This incriminated rupture of the
      soft, lipid rich atheromatous plaque as the most common mechanism leading to
      acute MI. In the closing decade of the past century, estimates of coronary blood
      flow using TIMI flow grades and TIMI frame rates led to the central unifying
      concept that the early restoration of normal flow (TIMI grade 3) was linearly
      related to survival after reperfusion therapy whether it be achieved
      pharmacologically or mechanically. The coronary angiogram was also integral in
      establishing antiplatelet therapy as the preferred pharmacotherapeutic agents to
      be used in association with stent deployment compared to coumarin drugs in
      preventing stent thrombosis. Although the coronary catheter is now used to
      deliver newer intracoronary devices such as intravascular ultrasound, velocity
      probes, gene probes and eluting catheters, it has served as the one indispensable
      form of coronary imaging for five successive decades. As such it has provided far
      more than is implied by the term "lumenology" and can rightly be called the lumen
      de lumine, the light of lights, for cardiovascular medicine.

PMID- 12053715
TI  - Thoughts on the diagnostic process.

PMID- 12053716
TI  - Hormones and heart disease: what we thought, what we have learned, what we still
      need to know.
AB  - Hormone replacement therapy has previously been recommended for the prevention
      and treatment of many conditions affecting women as they age. Decades of research
      have determined many beneficial biologic effects of hormones on the direct and
      indirect mechanisms of atherosclerosis. Observational studies have furthered the
      enthusiasm for hormone use with estimates of 35-50% reduction in risk for future
      cardiovascular events in women who took estrogens at menopause. However, there
      may be inherent selection and compliance biases in the non-randomized cohort
      methodology. The last decade has produced important randomized clinical trial
      results which now question whether estrogen replacement will reduce risks or even
      potentially increase cardiovascular event rates, particularly in women with known
      coronary disease within the first 1-2 years of initiating treatment. Conclusive
      evidence of the true risk:benefit ratio for hormone use after menopause awaits
      the completion of ongoing clinical trials. Until those results are available,
      each decision for postmenopausal hormone use must be made on a case-by-case basis
      weighing individual risks with the positive and negative aspects of therapy.

PMID- 12053717
TI  - Recognizing the real threat of biological terror.
AB  - Weapons of mass destruction can be used to harm and terrorize populations. Such
      weapons include those with chemical, nuclear or biological properties. Obviously
      computer viruses can add additional barriers to a quick response. The most
      effective, least costly and greatest threats are biologicals. Biological terror
      is not new, and biological weapons have been used for centuries. However, as a
      result of modern technology, the risks are greater now and the outcomes more
      terrible. Today they include live pathogens, various toxins, and theoretically
      "bioregulators"--biochemicals affecting cell signaling. Altered cell signaling
      could be used to induce apoptosis-cell death, or a heightened outpouring of
      cytokines mimicking overwhelming sepsis, or even an intracellular, biochemical
      "strike" causing cellular paralysis. Biological weaponeers now have the
      frightening ability to alter the genetic makeup of pathogens, rendering them
      resistant not only to available antibiotic therapy but also to currently
      effective vaccines. In dark corners of some fringe groups, bioweaponeers are
      searching for the capability of designing pathogens that target specific races,
      by virtue of discriminating ligands (1). The resulting morbidity and mortality
      from use of any biological weapons will be accompanied by chaos, governmental and
      social instability, panic, an extraordinary utilization of available resources,
      and an ongoing epidemic of sleepless nights (2,3). Herein I will review some of
      the issues and some of the currently available biological weapons. The major goal
      is to highlight the clinical presentations of patients with infections that could
      be used as biological weapons.

PMID- 12053718
TI  - Randomized trials of high-dose chemotherapy in breast cancer: fraud, the press
      and the data (or lessons learned in medical policy governing clinical research).
AB  - High dose therapy for breast cancer remains controversial. Of the 15 randomized
      trials of high dose therapy in breast cancer reported to date, two South African
      studies have been discredited leaving 13 remaining studies. Mortality was
      consistently low, in the 0 to 2.5% range, except for the BCNU containing American
      Intergroup study, which had a 7.4% toxic mortality rate. Seven of the remaining
      13 studies randomized fewer than 200 patients. Three of these small studies have
      significant differences in disease free survival, and a fourth study has a trend
      in favor of high dose therapy. The other three small studies cannot exclude a
      survival difference of 20%. Of the 6 remaining moderately large trials of 219 to
      885 randomized patients, 5 are adjuvant studies and one included patients with
      metastatic disease. Of the five adjuvant trials, four have significant
      differences in relapse rate favoring the high dose arm, and the remaining study
      has a trend (with a high dose sequential single agent design rather than
      combination therapy as in the other studies). A planned subset analysis of the
      first 284 patients in the largest study funded by the Dutch insurance industry
      showed a significant advantage for high dose therapy. Given the 2-year median
      time to relapse and an addition 2-year median to death after relapse, the follow
      up for survival of 3-5 years on these studies is still short. In the only
      moderately sized metastatic trial from the National Cancer Institute of Canada
      with a very short median follow-up of 19 months, a significant difference in
      disease free survival has emerged, with no difference in survival.

PMID- 12053719
TI  - Thrombocytosis: too much of a good thing?
AB  - Thrombocytosis is due to (a) a variety of disorders that cause reactive
      stimulation of platelet production, (b) familial mutations, or (c) essential
      thrombocythemia (ET) and other myeloproliferative disorders (MPDs). The MPDs are
      clonal abnormalities of the pluripotent hematopoietic stem cell. Dysregulation of
      megakaryocytopoiesis in ET involves defective binding of thrombopoietin by
      platelets and megakaryocytes resulting in increased levels of plasma free
      thrombopoietin, and increased sensitivity of megakaryocytes to thrombopoietin
      leading to their increased proliferation. Bleeding and thrombosis are the major
      causes of morbidity and mortality in ET and the other MPDs. The elevated platelet
      count and qualitative platelet defects have been implicated in the
      pathophysiology of these hemostatic problems. However, these platelet
      abnormalities do not correlate well with clinical complications. It is proposed
      that bleeding and thrombosis could be due to vascular abnormalities that result
      from dysfunctional hematopoietic stem cell-derived endothelial cells.

PMID- 12053720
TI  - "Managing the unmanageable" the U.S. Department of Health and Human Services,
      1989-1993.
AB  - The author served as the 17th U.S. Secretary of Health and Human Services, from
      March 1, 1989 until January 20, 1993. The department had 250 programs and 38
      percent of the expenditures of the federal government ($600.0 billion), the
      fourth largest budget in the world. The history of the department included the
      fact that the tenure of previous Secretaries had ranged from only eight months up
      to 37 months, and had averaged 27.5 months, resulting in the view that the
      department was unmanageable. The author's tenure as Secretary was 47 months, and,
      in the author's view, the department was indeed manageable. The United States
      Department of Health, Education and Welfare (DHEW) was created as a cabinet
      agency in 1953, during the administration of President Dwight D. Eisenhower. The
      Department was formed by bringing together the Social Security Administration
      (founded in 1935), the United States Commissioner of Education, and the United
      States Public Health Service (founded in 1798) to serve the United States
      Merchant Marines). This new cabinet department contained the nation's major
      domestic programs concerned with income security, public health and education.
      Oveta Culp Hobby of Texas was the first Secretary of the Department. By 1989, the
      department's programs had increased to more than 250, including Medicare,
      Medicaid, Headstart, Welfare, and others. During the administration of President
      Jimmy Carter, the Education programs were separated into a new cabinet agency,
      the U.S. Department of Education, and the name of the U.S. Department of Health,
      Education and Welfare became the U.S. Department of Health and Human Services
      (DHHS).

PMID- 12053721
TI  - The Gordon Wilson Lecture. The Mayo model: one path to an academic medical
      center.

PMID- 12053722
TI  - Memorial. James J. Cerda, M.D. 1930-2001.

PMID- 12053723
TI  - Memorial. Harper K. Hellems, M.D. 1920-1999.

PMID- 12053724
TI  - Memorial. Thomas E. Van Metre, Jr. 1923-1996.

PMID- 12053725
TI  - Memorial. Major General Robert E. Blount 1908-2000.

PMID- 12053726
TI  - Local probe techniques.

PMID- 12053728
TI  - The biophysics of sensory cells of the inner ear examined by atomic force
      microscopy and patch clamp.

PMID- 12053729
TI  - Biotechnological applications of atomic force microscopy.

PMID- 12053727
TI  - Molecular recognition studies using the atomic force microscope.

PMID- 12053730
TI  - Cellular membranes studied by photonic force microscopy.

PMID- 12053731
TI  - Methods for biological probe microscopy in aqueous fluids.

PMID- 12053732
TI  - Supported lipid bilayers as effective substrates for atomic force microscopy.
AB  - Supported lipid bilayers offer a diverse set of substrates for AFM investigations
      of both water-soluble samples and integral membrane proteins. Although their
      amphipathic nature is necessary for the latter specimens, it is their robustness
      and easily changed surface characteristics that make these surfaces particularly
      attractive for the former ones. When starting any AFM investigation of water
      soluble biological complexes, it is probably best to try mica first, owing to its
      remarkable effectiveness with a wide range of samples. Yet, if mica should prove
      inadequate, supported lipid bilayers are, as demonstrated here, a sensible second
      choice.

PMID- 12053733
TI  - Cryo-atomic force microscopy.

PMID- 12053734
TI  - Conformations, flexibility, and interactions observed on individual membrane
      proteins by atomic force microscopy.

PMID- 12053736
TI  - Forced unfolding of single proteins.

PMID- 12053735
TI  - Single-molecule force measurements.

PMID- 12053737
TI  - The atomic force microscope in the study of membrane fusion and exocytosis.

PMID- 12053738
TI  - Developments in dynamic force microscopy and spectroscopy.

PMID- 12053739
TI  - Scanning force microscopy studies on the structure and dynamics of single DNA
      molecules.

PMID- 12053740
TI  - Atomic force microscope imaging of cells and membranes.

PMID- 12053741
TI  - Measuring the elastic properties of living cells by the atomic force microscope.
AB  - In this chapter I discussed the possibility of measuring elastic properties of
      living cells by AFM. One reason for using the AFM for this purpose is its ability
      to both measure locally the mechanics of a cell and to distinguish different
      regions of the cell. Since the AFM can be operated under physiological conditions
      cellular processes can be followed, for example, cytokinesis and the
      investigation of the migration of cells.

PMID- 12053742
TI  - Cell adhesion measured by force spectroscopy on living cells.

PMID- 12053743
TI  - Eighteenth-century "monsters" and nineteenth-century "freaks": reading the
      maternally marked child.

PMID- 12053744
TI  - Life stories: in response to Deborah Minter.

PMID- 12053746
TI  - Friends in need: illness and friendship in adolescent fiction.

PMID- 12053745
TI  - Samantha: a story in pictures.

PMID- 12053747
TI  - An annotated bibliography of death-related books for children and adolescents.

PMID- 12053749
TI  - Jacques Doillon's Ponette: the perennial mourning child.

PMID- 12053748
TI  - Leeches and leprosy: medieval medicine in modern novels for young readers.

PMID- 12053750
TI  - "An infallible nostrum": female husbands and greensick girls in eighteenth
      century England.

PMID- 12053751
TI  - Research shows: a narrative of teaching and learning.

PMID- 12053752
TI  - Life as a literary laboratory.

PMID- 12053753
TI  - Literature, medicine and children.

PMID- 12053754
TI  - [Bone quality and fracture susceptibility].
AB  - Prevention of fractures brings about the effort to eliminate their potential
      causes. Osteoporosis syndrome belongs to the most frequent causes of the bone
      fractures. The use of densitometric methods may bring an overestimation of the
      bone quantity. Because of the independent contribution to mechanical resistance,
      the bone quality needs to be also evaluated. Qualitative changes of the bone can
      occur at the level of the bone as an organ, or at levels of its components-
      cortex, spongiosis and bone matrix. Bone quality is influenced mainly
      genetically; however, it can deteriorate also with age or in some diseases.
      Measurement of the bone quality is not yet practically accessible. Some
      ultrasonographic methods have a character of qualitative assessment. Osteoporosis
      can worsen the bone quality at different levels.

PMID- 12053755
TI  - [Changes in levels of acute phase proteins in patients with central
      hypercortisolism].
AB  - BACKGROUND: Acute phase protein reaction depends on complex interaction of
      proinflammatory cytokines and hormones, especially glucocorticoids.
      Glucocorticoids are essential factors for hepatocellular microenvironment and
      proteosynthesis during both rest and inflammatory period. Cushing's disease
      represents a model of glucocorticoid hyperstimulation of acute phase protein
      synthesis without interleukin-6 and other cytokine influence. METHODS AND
      RESULTS: 20 patients (age of 38 +/- 11, 11 males, 9 females) with a diagnosis of
      central hypercorticolism were examined. Plasma levels of 11 acute phase proteins
      were estimated. These results were compared with plasma ACTH, interleukin-6, and
      U-cortisol concentrations and correlated to the control group (healthy
      volunteers, age 30 +/- 5, 13 males, 7 females). Plasma levels of albumin and
      prealbumin in patients with Cusing's disease were significantly lower. We proved
      significant elevation of alpha 1-acid glycoprotein, haemopexin, and fibrinogen
      compared with healthy subjects. The positive correlation of alpha 1-acid
      glycoprotein and U-cortisol (r = 0.51, p < 0.01), haemopexin and U-cortisol (r =
      0.47, p < 0.05) respectively was found. CONCLUSIONS: The interaction between
      glucocorticoids and proinflammatory cytokines in acute phase protein synthesis
      depends on permissive effects of corticoids on cytokine signal transduction in
      hepatocytes. However, our results document that corticoida themselves
      significantly stimulate acute phase protein synthesis, and this stimulation
      differs from inflammatory pattern of hepatic proteosynthesis.

PMID- 12053756
TI  - [Effect of fibrates on VLDL and LDL lipoprotein composition and parameters of
      their oxidation in hypertriglyceridemia].
AB  - BACKGROUND: Meta-analyses of epidemiological studies proved that
      hypertriacylglycerolemia (HTAG) is an independent CHD risk factor. The VLDL
      lipoproteins, which are the main TAG carrier, are precursors of atherogenic LDL
      and their increased concentration is related to the decrease of antiatherogenic
      HDL, increased ratio of small, dense LDL and represents one of the causes of the
      endothelial dysfunction. According to some authors, HTAG is one of the factors of
      the oxidation stress. MATERIAL AND METHODS: 45 patients of the studied group
      received 200 mg of micronized fenofibrate per day for six weeks. Before the
      beginning and after the end of treatment, following examinations were carried
      out: concentration of plasma lipids, lipoproteins, and apolipoproteins,
      composition of fatty acids (FA) in main lipid plasma classes and LDL
      (phosphatidylcholine--PC, TAG, cholesteryl esters--CE) and lipoperoxidation in
      VLDL and LDL, isolated by preparative ultracentrifugation. RESULTS AND
      CONCLUSIONS: In plasma, the treatment of HTAG led to a significant decrease of
      TC, TAG and apo-B concentration and to the increase of cholesterol concentration
      in HDL and in both HDL2 and HDL3 subfractions. In isolated LDL particles we
      observed a decrease of the TAG portion (by 25%) together with significant lag
      phase prolongation (by 33%, P < 0.05) and peak time retardation (by 24%, P <
      0.05). In VLDL particles the concentration of cholesterol became smaller (by
      28%), TAG (by 26%), phospholipids (by 28%) (in all groups P < 0.005) and the lag
      phase became significantly longer (by 16%, P < 0.01). Treatment with fenofibrate
      significantly reduced the linoleic acid (18:2n-6) in PC and TAG plasma, CE and TG
      LDL, in a higher ratio of palmitoleic acid (16:1n-7) in CE LDL, oleic (18:1n-9)
      in PC LDL, in significant concentration of total monoenic FA in PC and CE LDL and
      to a significant increase of the concentration of myristic acid (14:0) in CE and
      myristic and stearic acids (18:0) in TAG LDL. From our results it is possible to
      conclude that the six-week long treatment of HTAG with micronized phenofibrate
      led to significant modification of LDL and VLDL composition accompanied by their
      lower lipoperoxidation indexes. These favourable changes in oxidability were
      accompanied with changes in the composition of FA in CE, TAG and PC plasma as
      well as LDL.

PMID- 12053757
TI  - [Occult fecal blood loss--comparison of immunochemical and biochemical tests].
AB  - BACKGROUND: Test of occult fecal blood loss belongs to the basic diagnostic
      procedures in gastroenterology. That examination is introductory method for
      screening, diagnosis and dispensarization of patients with colorectal cancer.
      Most frequently used tests in practice are biochemical and immunochemical tests.
      The aim of the study was to compare the results and clinical contribution of both
      kinds of tests. METHODS AND RESULTS: The results of immunochemical test Immocare
      (Care Diagnostica) and biochemical test Haemoccult (Rohm Pharma) were compared in
      a group of 253 patients (131 women, 122 men, average age 52.6 yr, range 19-88
      yr). In all patients total coloscopy was subsequently performed. Sensitivity of
      immunochemical test was clearly higher (61.2%) than of biochemical test (29.4%),
      specificity was slight lower (95%, resp. 98%). Accuracy of Immocare test was also
      higher (82% than 72% of Haemoccult). CONCLUSIONS: Our results confirm advantages
      and competency of Haemoccult test for screening and dispensary programmes. More
      expensive and more difficult Immocare test is suitable for examination of
      symptomatic or risk patients.

PMID- 12053758
TI  - [Evaluation of trends in ue of antibiotics and resistance in selected bacterial
      pathogens].
AB  - BACKGROUND: Evaluation of antibiotic consumption and the surveillance of
      bacterial pathogens resistance appears to be an indispensable part of antibiotic
      policy. The aim of this study was to evaluate dynamics of antibiotics consumption
      and resistance development in selected bacterial strains (Pseudomonas
      aueruginosa, Staphylococcus aureus and Staphylococcus epidermidis) in the
      environment of Faculty Hospital. METHODS AND RESULTS: The analysis was focused on
      the development of antibiotic consumption and monitoring of the development of
      bacterial resistance. Samples were taken in internal and surgical departments of
      General Faculty Hospital in Prague in 1992, 1995, and 1999. The evaluation of
      antibiotic consumption was based on Anatomical Therapeutic and Chemical
      classification system and the Defined Daily Doses (DDD). The consumption in the
      follow up period almost doubled in surgical department while in internal medicine
      department was decreased by almost one third. In both department, namely in the
      surgical one significant increase of bacterial resistance of tested antibiotics
      was noted. CONCLUSION: The important part of the local antibiotic policy is the
      monitoring of development of bacterial resistance and consumption of antibiotics.

PMID- 12053759
TI  - [Biothesiometry in the diagnosis of peripheral neuropathies].
AB  - The aim of review is to give basic information on the method of peripheral
      neuropathy examination using biothesiometry technique. Impaired vibratory
      threshold can be identified in all patients with peripheral neuropathies, the
      diabetic, uremic, alcoholic or paraneoplastic ones. It is a simple, sensitive and
      comfortable method for daily screening. On the other hand it is sufficiently
      sensitive for detection and evaluation of peripheral neuropathy. Principle is a
      vibrating probe, vibration amplitude can be changed by voltage adjustment.
      Biothesiometry is used in diagnostics of peripheral neuropathies with impaired
      vibratory perception threshold, mainly in diabetology and neurology.

PMID- 12053760
TI  - [History of the Institute for Clinical and Experimental Medicine (IKEM), a
      research institute for experimental therapy].

PMID- 12053761
TI  - Atrial natriuretic peptide in the granular cells of the snail heart.
AB  - Cardiomyocytes of vertebrates combine contractile and endocrine functions. They
      synthesize and secrete atrial natriuretic peptide (ANP), which is localized in
      their specific granules. The presence of ANP has been shown in some tissues of
      invertebrates, including the heart of molluscs. We have studied localization of
      ANP in cells of the snail heart. METHOD: The atrial and ventricular tissues of
      the snail Helix pomatia were studied by electron microscope immunocytochemistry,
      using anti-ANP antibodies. ANP-immunoreactivity has been detected in granules of
      granular cells located on the luminal surface of the snail myocardium. These
      cells are abundant in the atrium being very rare in the ventricle. Granular cells
      at different stages of maturation were revealed. Immature granular cells have
      light granules of moderate size with homogeneous tight content, while mature
      granular cells are huge in size and all their granules are fused together. The
      material of these granules loosens up and almost completely fills up the
      cytoplasm. No ANP-immunoreactivity was observed in muscle cells or nerve fibers.
      A possible origin of granular cells from the cardiac endothelial cells is
      discussed. The molluscan heart, similar to that of vertebrates, is a bifunctional
      organ. However, contrary to the heart of vertebrates, in the molluscan heart
      contractile and endocrine functions are separated between different types of
      cells.

PMID- 12053762
TI  - [Disruption of organization of mitotic microtubules in root meristem cells of
      Allium cepa induced by chloral hydrate].
AB  - Data are presented on the effect of chlorahydrate on microtubule organization in
      the root meristem of Allium cepa. Our studies show that an incomplete preprophase
      band commonly appears during G2-prophase transition, yet the major effect is the
      lack of perinuclear microtubules, leading to inhibition of the prophase spindle
      formation and transition to C-mitosis. Upon chloralhydrate treatment of metaphase
      cells, we found cells with chromosomes regularly aligned within the metaphase
      plate and differently disorganized mitotic spindles. Concurrently, C-metaphase
      cells with remnants of kinetochore fibers were present. In addition, normal
      bipolar and abnormal irregular types of chromosome segregation were detected,
      this representing multipolar and diffuse anaphases. The major difference between
      them is the presence of polar microtubules during multipolar anaphase, and their
      lacking during diffuse anaphase. Alternatively, microtubule clusters between
      segregated groups of chromosomes are typical for cells with diffuse anaphase.
      During bipolar anaphase, excessive aster-like microtubules emanate from the
      spindle poles, and in telophase accessory phragmoplasts are observed at the cell
      periphery. The formation of incomplete phragmoplasts was observed after normal
      bipolar and abnormal chromosome segregation. We conclude that chloralhydrate may
      affect the nuclear surface capability to initiate the growth of perinuclear
      microtubules, thus blocking the prophase spindle formation. It also disturbs the
      spatial interaction between microtubules, which is crucial for the formation and
      functioning of various microtubular systems (preprophase band, spindle and
      phragmoplast).

PMID- 12053763
TI  - [Ultrastructural and morphometric characteristics of cardiomyocyte
      mitochondriomes of several invertebrate species. II. Heart ventricle
      cardiomyocyte mitochondriome of several gastropod mollusks].
AB  - The mitochondrial ultrastructure in ventricle cardiomyocytes of three gastropod
      molluscs (Clione limacina, Helix pomatia, Lymnaea stagnalis) has been studied.
      Mitochondria in cardiomyocytes of these molluscs are connected by
      intermitochondrial contacts of the same morphology as intermitochondrial contacts
      in vertebrate cardiomyocytes. Their numbers in cardiomyocytes of the above
      molluscs being, respectively, 61, 35.1 and 29.2 contacts per 100 mitochondria. In
      Clione limacina cardiomyocyte contractile elements located on the periphery of
      cell occupy 21.1% of the cytoplasm volume. Mitochondria form a core making large
      dense central accumulations taking up 54.9% of the cytoplasm volume. Numerous
      mitochondria have vesicular or tubular cristae and light matrix. Unlike
      cardiomyocytes of Clione limacina, in Helix pomatia and Lymnaea stagnalis
      contractile material predominates in cardiomyocytes occupying 43.7% and 49.2% of
      the cytoplasm volume, respectively. Mitochondria located on the periphery and in
      the center of cardiomyocytes in Lymnaea stagnalis and Helix pomatia occupy 31 and
      32.5% of the cytoplasma volume, respectively. Mitochondria in cardiomyocytes of
      both these molluscs have plastic cristae and dense matrix. The differences in
      cardiomyocyte mitochondriom organization in the studied molluscs can be explained
      by different functional heart loading in these due to different levels of their
      locomotor activity.

PMID- 12053764
TI  - [Morphological changes in the parr masou salmon Oncorhynchus masou retina in
      experimental change of geomagnetic field].
AB  - Topography of photoreceptor cells in young salmon Oncorhynchus masou retina,
      their properties and morphology of cellular organelles in external and internal
      segments of photoceptors have been first described. Morphological changes of
      retina cells were analysed in day and night time, and also in the experiment for
      indemnification of geomagnetic field (GMF) in the body of the aquarium. A
      comparison of retina structure in fishes of night and day time controls with that
      in experimental fishes has shown that the external cone segments in the latter
      occupy, in relation to the external limiting membrane, an intermediate position,
      characteristic of retinae exposed to twilight lighting. It is supposed that GMF
      indemnification was equivalent to weak light pulse, which, however, could
      considerably change melatonin production by retina photoreceptor cells. Thus, at
      experimental indemnification of GMF, retina sensitive cells demonstrate typical
      retinomotor response. Some ultrastructural changes in retina cells were also
      detected, in particular, size changes in ribbon synapses in rod and cone
      terminations. In addition, nematosomes appeared in the internal nuclear layer,
      and in the spinules, i.e. digitiform invaginations of terminal dentrites of
      horizontal cells into cone nervous terminations, the quantity of an electron
      dense material was noticeably magnified in comparison with a night control. The
      noted changes testify, in our opinion, to essential modifications in metabolic
      processes of retina photoreceptors under effect of GMF variations, in particular,
      to changes in retinal melatonin synthesis.

PMID- 12053765
TI  - [Differences in the character of interaction of normal and transformed human
      keratinocytes with laminin isoforms].
AB  - Laminins constitute a family of heterotrimeric glycoproteins of basement
      membranes. Laminins promote cell adhesion, migration, growth, and
      differentiation. So far, at least 12 different isoforms of laminin have been
      known. However, no sufficient knowledge is available on the nature of cell
      response on different laminins. The study was aimed to compare adhesive
      properties of two laminin isoforms, laminin-1 and laminin-2/4, with respect to
      normal (freshly isolated keratinocytes) and transformed (A-431) human skin cells.
      We have used the following assays: cell adhesion to the substrate covered with
      laminin isoformes, interaction of latex beads (D = 1 micron) coated with the same
      proteins with cells in suspension, and a comparative study of the cytoskeleton
      structure of cells spread on the immobilized laminins. It was demonstrated that
      laminin-2/4 is a more effective potent promotor of adhesion for both normal
      keratinocytes and transformed A-431 cells, compared with laminin-1. A comparison
      of many attached protein-covered beads allowed to estimate a relative quantity of
      cell surface receptors to laminin isoforms in different cell types. The relative
      number of receptors to laminin-2/4 on the keratinocyte surface is 7 times higher
      than that to laminin-1 after a 30 min incubation with cells, and is 6 times
      higher after 1 hour. As for A-431 cells, their attachment to laminin-2/4 beads is
      5 times higher than that to laminin-1-beads after a 1 min incubation, but as
      early as after 5 min this distinction disappeared, owing to bead internalization.
      The presence of a specific receptor to laminin-2/4 but not to laminin-1 on the
      keratinocyte surface has been suggested. Keratin differences in cytoskeleton
      organization in normal and transformed skin cells spread on the substrates
      covered with laminin-1 and laminin-2/4 were demonstrated.

PMID- 12053766
TI  - [Reproductive development of initial sporophytes in Pinus sylvestris L].
AB  - The reproductive development of Pinus sylvestris from generative primordia to
      sporophyte initial (embryo tier of 16-celled proembryo) was studied. In the
      reproductive cycle, three types of stages are distinguished and described in
      association with: 1) hereditary program formation; 2) a new reproductive initial
      origin, and 3) increase in propogative energy. The layout of disposition of these
      stages in the reproductive cycle is given.

PMID- 12053767
TI  - [Effect of bemythyl on carbohydrate metabolism in cirrhotic rat liver].
AB  - Effect of actoprotector bemitil (2-ethylthiobenzimidazole hydrobromide) on
      glycogen content and activities of glycogen synthase, glycogen phosphorylase, and
      glucose-6-phosphatase was studied in cirrhotically altered rat liver. The
      contents of glycogen and its fraction were determined a cytofluorimetrically
      (Kudryavtseva et al., 1974). In cirrhosis, the total glycogen content in
      hepatocytes increases by nearly 3 times, while the amount of a stable fraction of
      glycogen rises by 7.5 times. Glucose-6-phosphatase activity fell to the level of
      25% compare to the norm. Activities of glycogen synthase and glycogen
      phosphorylase in the cirrhotic liver did not differ from the norm. In
      cirrhotically altered liver, bemitil produced a decrease in the total glycogen
      content due to a decrease in glycogen synthase activity in an increase in glucose
      6-phosphatase and glycogen phosphorylase activities. The above results suggest a
      favorable effect of bemitil on cirrhotic liver.

PMID- 12053768
TI  - [Distribution of RNA polymerase II in nuclei of early murine embryos].
AB  - Nuclear distribution of unphosphorylated and phosphorylated forms of RNA
      polymerase II in two celled mouse embryos was studied using immunoelectron
      microscopy. RNA polymerase II was shown to be present in the karyoplasm of mouse
      embryo nuclei at the early two-celled stage, that is before activation of the
      embryonic genome. During this period, RNA polymerase II is diffusely localized in
      the nuclei being not associated with any nuclear domains. After embryonic genome
      activation, the pattern of the nuclear distribution of RNA polymerase II is
      changed. At the late two-celled stage, its prominent part is deposited in
      pronucleoli, as well as in interchromatin granule clusters and perichromatin
      fibrils. At this stage, unphosphorylated RNA polymerase II is mainly associated
      with perichromatin fibrils. The obtained data fit well with the notion of the
      coordinated distribution of RNA polymerase II and splicing factors, and of their
      association with the same nuclear domains.

PMID- 12053769
TI  - [Characteristics of endoribonuclease activity of proteasomes from K562 cells. I.
      Dependence of RNAase activity of proteasome and alph-RNP on conditions of
      endonucleolysis reaction].
AB  - Proteosomes from human proerythroleukaemic cell line K562 are found to degrade
      high molecular weight cytoplasmic RNAs, particularly ribosomal and specific
      messenger RNA. This activity was observed to be endoribonucleotylic. The
      induction of differentiation by erythroid pathway in K562 cells invokes
      augmentation of endonuclease activity in proteasomes. The number of
      characteristics of this enzymatic activity was investigated. Specificity of
      endonuclease of these RNPs is shown to be Ca- and Mg-dependent. Dephosphorylation
      of protein subunits suppresses RNase activity of proteasomes. Endonuclease of
      proteasomes is thermolabile. The examined activity depends on the secondary
      structure of substrate RNA. Protein subunits are responsible for ribonuclease
      activity of proteasomes rather than for low molecular weight RNAs associated with
      the complex.

PMID- 12053770
TI  - [Inducible nitric oxide synthase in rat lungs in experimental bronchial asthma
      and its status in administering drugs with adrenergic action].
AB  - The state of inducible NO-synthase (iNOs) in the rat lung with experimental model
      of bronchial asthma (BA) was studied after administrating short-acting beta 2
      agonist fenoterol, long-acting beta 2-agonist salmeterol, and adrenoblocker
      propranolol. Administrated beta 2-agonists were observed to result in reducing
      iNOs activity in the rats with BA, while propranolol intensified iNOs expression.

PMID- 12053771
TI  - [Search for a molecular determinant in phosphatidylinositol-3-kinase molecules,
      involved in the interaction with the beta-gamma-G protein dimer].
AB  - The heterodimer p85/p110 and p101/p120 gamma phosphatidylinositol-3-kinases
      (PI3K) are important effector proteins in the signal transduction in a cell. beta
      gamma-subunits of heterotrimetic G-proteins are some of the main regulators of
      PI3K functional activity. Molecular determinants in the molecules of PI3K which
      may be responsible for coupling with beta gamma-dimer, remain obscure. The aim of
      this work was to identify the determinants of the basis of a comparative analysis
      of primary structures of PI3K and other beta gamma-binding proteins (adenylyl
      cyclases of the different types, G-protein-coupled receptor kinases,
      phospholypase C beta). The obtained data enables us to make some conclusions. In
      p85/p110 PI3K, beta gamma-binding determinants are located mainly in its
      regulatory subunit (BCR-domain, inter-SH2-domain). However, the interaction
      between beta gamma and catalytic domain of the catalytic p-110 subunit is also
      possible. In p101/p120 gamma PI3K, beta gamma-binding regions are located only in
      the catalytic p120 gamma-subunit of the enzyme, i.e. in its middle part and C
      terminal catalytic domain regions of 436-502, 791-822 and 911-1000). In spite of
      the fact that potential beta gamma-binding regions are localized in different
      loci of PI3K subunits, they can form a compact beta gamma-binding surface in the
      process of its molecule folding, similar by as in other beta gamma-binding
      proteins.

PMID- 12053773
TI  - [Recognition of cell patterns and prospects of applying it in analytical
      microscopy].
AB  - On the base of multiparametric analysis of scanograms, a method of creation of
      cell patterns and of their recognition in n-dimensional space is suggested. The
      prospects of its application in the analytic microscopy and in differential
      diagnostics of diseases are discussed.

PMID- 12053772
TI  - [Optimization of conditions for isolating chromosomes in flow sorting].
AB  - Factors for purity and efficiency of flow chromosome sorting were analysed on the
      base of quantitative analysis. The sorting rate and relative purity of individual
      chromosome fractions are determined both by the quality of initial chromosome
      suspension, instrument parameters and gate position on experimental histograms.
      The described procedure of analysing sorting efficiency and fraction purity
      allowed to formulate general tips for optimization of sorting conditions
      depending on a given strategy: maximization of quantity of obtained material, or
      achieving maximum purity for sorted fraction. The analysis is carried out on the
      bases of chromosome distribution parameters: their relative halfwidths and
      distances. These parameters can be obtained by the quantitative analysis programs
      for flow cytometry data. It is shown that the critical parameter for sorting
      purity is the level of contaminated objects in a zone of sorted chromosome signal
      registration. In addition, the fraction purity depends on the cover extent
      between different chromosome distributions. Created procedure allows to build up
      nomograms linking the sorting efficiency with fraction purity, depending on the
      position of sorting gates. These monograms permit to determine the position of
      sorting gates in relation to one or another strategy: 1) maximum rate for
      chromosome material obtaining, 2) maximum fraction purity, or 3) compromise
      between the two. The presented analysis allows to optimize the chromosome sorting
      process for subsequent genome investigations providing chromosome material with
      controlled characteristics.

PMID- 12053774
TI  - [Aging as a metagenetic process].
AB  - Genomes of eukaryotic cells are so complicated that spontaneous processes lead
      inevitably to a continuous formation of egoistic genetic elements from the normal
      ones. These elements convert the intracellular Cosmos into Chaos and therefore
      they can be named chaonogenes. They behave as endogenous genetic parasites and
      are able to evaluate. The rate of their evolution is very rapid, which unevitably
      results in senescence and death of not only cells and multicellular organisms but
      also of populations and species, because chaonogens are transmitted from somatic
      cells to gametes. Populations of chaonogenes are very sensitive to environmental
      changes, and different sets of intracellular or extracellular changes are
      commonly used in nature to put obstracles in deleterious evolution of chaonogenes
      or to stop their evolution. These changes can be moderate (as at mitosis) or
      crude (as at meiosis), or they can be predicted (as programmed biochemical
      changes in the course of mitosis, meiosis and gametogenesis) or unpredicred
      (mutations, somatic crossingover, random association of gamets), but in all the
      cases they lead eventually to some degree of rejuvenation. In somatic cell
      populations, the process of senescence in slowed down by means of epigenetically
      determined changes and mitotic divisions, at which both kinds of changes
      (programmed and accidental) are moderate, and for this reason only a small part
      of dividing cells dies. At meiosis both kinds of changes are so acute that the
      majority of cells die, but the formation of gametes and zygotes becomes almost
      completely rejuvenated. Only mutations leading to very acute changes in
      intracellular conditions (whose products act on chaonogenes similarly as new
      antibiotics on bacteria) can save aging populations of multicellular organisms
      from death (as do L. N. Gumilev's "mutations of passionarity"), and only
      accidentally appearing "catastrophic" macromutations can give rise to new (and,
      of the same time, young) species. It is concluded that the induction of acute
      temporal biochemical changes in the inner environment is to slow down processes
      of human senescence and to lead to rejuvenation.

PMID- 12053775
TI  - [Trends in the incidence of hepatic tumors in childhood].
AB  - OBJECTIVE: To evaluate the incidence trends of hepatic tumors among children
      living in Mexico City. MATERIAL AND METHODS: A cross-sectional hospital survey
      was conducted to yield two databases. The first database contains the registry of
      all the cases of hepatic tumors occurring during the period 1982-1991, in public
      hospitals of Mexico City. The second database contains all hepatic tumor cases
      found between 1996 and 1999 in Hospital de Pediatria del Centro Medico Nacional
      "Siglo XXI" and in Hospital General del Centro Medico La Raza, both hospitals
      pertaining to Instituto Mexicano del Seguro Social (Mexican Institute of Social
      Security). The average annual incidence rates (AAIR) were calculated for each
      type of hepatic tumor. The rates were standardized with the direct method, using
      as standard the world population under 15 years of age. The trends were evaluated
      with the annual incidence rates and the average rate of change assuming a Poisson
      distribution. RESULTS: The AAIR for hepatoblastoma during the period 1982-1991
      was three times higher for men than for women, with a value of 0.6 x 10(6). The
      group of 1-4 years of age was the most affected. For hepatocarcinomas the AAIR
      was two-fold for women (0.14) as compared to men. Between 1996-1999 the AAIR for
      hepatoblastoma was 5.11 in women and 1.85 in men. The age group with the highest
      rate was women under one year of age. The AAIR for hepatocarcinoma was 0.64 for
      males and 1.23 for females. The most affected age group was males aged 10 to 14
      years. No significant upward or downward trend was found in the incidence of
      hepatoblastomas. A non-significant change rate of 10% was found for
      hepatocarcinoma. CONCLUSIONS: No significant trends were observed in the
      incidence of hepatic tumors in children of Mexico City aged under 15 years,
      during the periods 1982-1991 and 1996-1999. The English version of this paper is
      available at: http://www.insp.mx/salud/index.html.

PMID- 12053776
TI  - Epidemiology of drug resistance: the case of Staphylococcus aureus and coagulase
      negative staphylococci infections.
AB  - OBJECTIVE: To study the activity of several antibiotics against Staphylococcus
      spp. MATERIAL AND METHODS: The study included 1209 strains of Staphylococcus spp.
      from two institutions; Instituto Nacional de Pediatria (National Institute of
      Pediatrics) and Hospital Infantil de Mexico Federico Gomez (Mexico City
      Children's Hospital). Minimum Inhibitory Concentrations of all antibiotics were
      determined by the agar macrodilution technique and standard methods from the
      National Committee for Clinical Laboratory Standards. RESULTS: Resistance of S.
      aureus was 14.2% and that of coagulase-negative staphylococci was 53.4%. The
      activity of different antibiotics is presented in detail. CONCLUSIONS:
      Surveillance of strains resistant to methicillin is necessary. The English
      version of this paper is available too at: http://www.insp.mx/salud/index.html.

PMID- 12053777
TI  - [Prevalence of hazardous and harmful consumption of alcohol in the insured
      population of the Mexican Social Security Institute].
AB  - OBJECTIVE: To estimate the prevalence of hazardous and harmful alcohol
      consumption among the insured population of Instituto Mexicano del Seguro Social
      (Mexican Social Security Institute, IMSS). MATERIAL AND METHODS: A cross
      sectional survey was conducted in 45,117 insured subjects from Mexico's 36
      political districts; study subjects were interviewed using a structured and self
      applied questionnaire on alcohol consumption, using the ten-item screening
      instrument AUDIT (Alcohol Use Disorder Identification Test). The first three
      questions refer to the amount and frequency of drinking, the following three
      question to alcohol dependence, and the last four to alcohol-related problems.
      Each item has three to five options and each is scored progressively from zero to
      four. The prevalence of alcohol consumption was estimated with 95% confidence
      intervals. RESULTS: The prevalence of problem drinkers (hazardous and harmful)
      was 12.8% (IC 95% 12.5-13.2); it was higher in men (22.2%; IC 95% 21.7-22.8) than
      in women (3.4%; IC 95% 3.1-3.6). An age effect was observed in men, while in
      women alcohol consumption was more homogeneous. In both genders consumption was
      higher in productive-age groups. CONCLUSIONS: The prevalence of hazardous and
      harmful alcohol consumption is high in the insured population of the IMSS in
      Mexico. There is a need to implement health policies and health programs to
      diminish this serious health problem. The English version of this paper is
      available at: http://www.insp.mx/salud/index.html.

PMID- 12053778
TI  - [Whom do Mexican adolescents talk to about AIDS?].
AB  - OBJECTIVE: To establish whether certain characteristics of the young influence
      their choice of people with whom to discuss AIDS. MATERIAL AND METHODS: A
      national survey was conducted in 1997 by the Consejo Nacional para la Prevencion
      y Control del SIDA (CONASIDA, Mexican Council for AIDS Prevention and Control).
      Study subjects were 4886 male and female 15-19 year-old teenagers. Multinomial
      logistic regression was used to analyze data. RESULTS: A model including the
      variables sex, sexual activity, work conditions, and father's schooling level,
      turned out to be significant and highly predictive of people with whom teenagers
      discuss AIDS, as compared to teenagers speaking with no one. Male teenagers
      discuss AIDS with their fathers more than female teenagers, and female teenagers
      discuss AIDS more with their mothers. Sexually active teenagers discuss AIDS more
      with their friends and less with their teachers than sexually inactive teenagers.
      The greater schooling level the father has, the more people teenagers have with
      whom to discuss AIDS and the more they discuss AIDS at home, compared to
      teenagers with fathers without schooling. CONCLUSIONS: Differentiated sexual
      education training strategies should be designed in accordance with
      subpopulations' characteristics. The English version of this paper is available
      at: http://www.insp.mx/salud/index.html.

PMID- 12053779
TI  - [Comparison of normal delivery care in the hospital and traditional care
      systems].
AB  - OBJECTIVE: To compare vaginal delivery hospital and traditional care systems to
      identify resources and practices, as well as maternal and neonatal complications
      related to each system. MATERIAL AND METHODS: Between 1989 and 1990, a cross
      sectional study was conducted in three hospitals of Merida City and four
      municipalities of the state of Yucatan. The study sample consisted of 205 women
      who had a normal vaginal delivery. Delivery procedures were observed and a
      questionnaire to identify complications was applied 15 days after childbirth.
      Data analysis consisted in comparison of proportions with the chi-squared test.
      RESULTS: Maternal and neonatal complications were identified in both systems;
      however, maternal complications were more frequent in hospital care, whereas
      neonatal complications were more frequent in traditional delivery care. The total
      number of complications was similar in the two systems. CONCLUSIONS: No
      difference was found in the quality of care between the hospital and the
      traditional systems. Observed complications may be attributable to resources and
      practices of each system. Additional studies should be conducted to evaluate the
      advantages and disadvantages of each system, as well as to improve the quality of
      maternal and child care. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12053780
TI  - [Seroprevalence of brucellosis in agricultural workers in the coastal zones of
      Castellon, Spain].
AB  - OBJECTIVE: To estimate the seroprevalence of brucellosis in agricultural workers.
      MATERIAL AND METHODS: This cross-sectional study was conducted between 1996 and
      1997 at Unidad de Salud Laboral del Centro de Salud Publica (CSP) in Castellon,
      Espana (Public Health Center Occupational Health Unit), among 482 subjects
      applying for certification to handle pesticides for agricultural use. Serologic
      testing consisted of rose Bengal staining, Wright's agglutination, and
      antibrucella Coombs tests: Statistical analysis consisted in estimation of
      prevalence figures and logistic regression modelling. RESULTS: Fifteen subjects
      (3.1%, 95% CI 1.8%-5.1%) had titers of 1/40 or higher to Wright and/or Coombs
      tests; all were negative to rose Bengal staining. No high occupational risk was
      observed. CONCLUSIONS: A low prevalence of brucellosis was found. The English
      version of this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 12053782
TI  - Clinicians and the economic evaluation of health.
AB  - Papers dealing with the economic evaluation of health care have proliferated in
      the clinical literature. They provide an evidence-based element to help policy
      makers allocate resources among competing projects. These studies are generally
      done from a the perspective of a health provider (public or practice) or a public
      health professional, they do not take into account the special nature of the
      patient-physician relationship. The value of these studies for a clinician caring
      for an individual patient is questioned because the perspective used and the
      values measured represent those of society or a health provider, not those of
      patients. In addition, since cost-effectiveness analysis fails to take into
      account important societal ethical beliefs that are relevant to the care of
      individuals, its application to individual care is limited. Physicians should use
      these analyses when working as private or public policy makers, not as
      clinicians. The English version of this paper is available too at:
      http://www.insp.mx/salud/index.html.

PMID- 12053781
TI  - The centennial of the Yellow Fever Commission and the use of informed consent in
      medical research.
AB  - The year 2000 marked the centennial of the discovery of the mode of transmission
      of yellow fever. Informed consent was systematically used for the first time in
      research. This process was the result of a complex social phenomenon involving
      the American Public Health Association, the US and Spanish Governments, American
      and Cuban scientists, the media, and civilian and military volunteers. The public
      health and medical communities face the AIDS pandemic at the beginning of the
      21st Century, as they faced the yellow fever epidemic at the beginning of the
      20th Century. Current medical research dilemmas have fueled the debate about the
      ethical conduct of research in human subjects. The AIDS pandemic is imposing
      enormous new ethical challenges on the conduct of medical research, especially in
      the developing world. Reflecting on the yellow fever experiments of 1900, lessons
      can be learned and applied to the current ethical challenges faced by the
      international public health research community. The English version of this paper
      is available too at: http://www.insp.mx/salud/index.html.

PMID- 12053783
TI  - [Statistics of hospital discharges in the public sector of the National Health
      System, 2000].

PMID- 12053784
TI  - [Association of oral lesions with HIV serological status].
AB  - OBJECTIVE: To estimate the prevalence of oral lesions and its association with
      HIV serological status. MATERIAL AND METHODS: A cross-sectional descriptive study
      was conducted between 1998 and 1999 in Mexico City, among 512 subjects attending
      two information centers of Centro Nacional para la Prevencion del VIH/SIDA e ITS
      (CONASIDA, National Center for Prevention of HIV/AIDS and Sexually Transmitted
      Infections) for HIV serologic testing. The oral examination was performed without
      knowledge of the HIV status. Statistical analysis was conducted using Student's t
      test, Fisher's exact test and the chi 2 test; odds ratios and 95% CI were also
      calculated. RESULTS: A total of 512 individuals were examined, 68 of whom were
      HIV-positive. HIV-related oral lesions (OL), were evident in 65% (44/68) of the
      HIV-positive individuals; 95% of them consisted in oral candidosis (OC) and hairy
      leukoplakia (HL). OC and HL were strongly associated with seropositivity to HIV.
      CONCLUSIONS: OC and HL were the oral lesions most strongly associated to HIV
      seropositivity. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12053785
TI  - [Interpretation of anthropometric indices in children in Arandas, Jalisco,
      Mexico].
AB  - OBJECTIVE: To assess the nutritional status of children attending the Instituto
      Alteno para el Desarrollo de Jalisco (Highlands Institute for Development of
      Jalisco State, Inadej) in Arandas, Jalisco and to discuss the classification
      criteria of infant malnutrition in Mexico. MATERIAL AND METHODS: A cross
      sectional study was conducted in 775 children aged between twelve and one hundred
      and twenty months, who attended Inadej, including 432 children recently
      registered in INADEJ. Measurements included weight/age, height/age, and
      weight/height indices. The prevalence of malnutrition was compared using the
      WHO's criteria and the Mexican Official Norm Classification (NOM-SSA) criteria.
      The weight/age, height/age and weight/height indices were compared using the chi
      squared test. RESULTS: Parents' schooling level was low (mean = 3.6 years); the
      mean family income was U.S. $198.00 dollars per month, with each family member
      receiving 0.56 dollars per day for three daily meals. The prevalence of
      malnutrition was significantly higher with any of the three indices when using
      the NOM-SSA criteria, as compared to the WHO criteria (weight/age 91.7 vs. 30.9%;
      height/age 66.9 vs 17.3%; and weight/height 62.5 vs. 9.5%, respectively).
      CONCLUSIONS: The weight/age index and the NOM-SSA criteria overestimate the
      prevalence of malnutrition and are not able to tell apart children with familial
      small size, nor those with acute and/or chronic or past malnutrition. The WHO
      criteria were found to be more useful; the weight/height (recent malnutrition)
      and height/age (chronic malnutrition) indices should be used for international
      comparisons. The English version of this paper is available at:
      http://www.insp.mx/salud/index.html.

PMID- 12053786
TI  - [Caring for a patient and not a disease isolated in its context].

PMID- 12053787
TI  - [Melancholy: from Hippocrates to DSM-IV].

PMID- 12053789
TI  - [Clinical aspects of acne].
AB  - Acne is the most current disease in clinical practice for dermatologist offices,
      where 15 to 20% of consultation have to deal with. If juvenile polymorphous acne
      is the most classical form, new aspects has been enhanced during these late
      years. Acne in new borns, prepubertal acne with hormonal secretions from
      surrenalians glands, late acne starting after 25 years, and leading to specific
      hormonal testing have been emphaized. Severe acne is happily much less frequent,
      but fulminans acne can start after the beginning of a treatment by isotretinoin.

PMID- 12053788
TI  - [Mechanisms and causes of acne].
AB  - Three pathogenic factors are closely involved in the mechanism of acne with a
      sequence beginning with seborrhea, then sebum retention, and finally
      inflammation. The sebaceous gland is a target of androgens. Acne may be related
      to an excessive sensitivity of sebaceous end-organs to androgens. However, in
      women, an ovarian or adrenal hyperandrogenism may be implicated. The cause of
      sebum retention is the hyperkeratinisation of the infra infundibulum of the
      sebaceous duct. Many factors, particularly the chemical composition of sebum in
      acne and the androgens are responsible for this hyperkeratinisation. The
      inflammation is related to the inflammatory role of the numerous enzymes of
      Propionibacterium acnes and to the chimiotactism of neutrophils. Other pathogenic
      factors may have a role in acne, particularly smoking and stress. The knowledge
      of these pathogenic factors and their evaluation in each patient are a main point
      for therapeutic strategy, because every available treatment has a special impact
      on such or such factor.

PMID- 12053790
TI  - [Induced acne].
AB  - Induced acne belongs to the clinical forms of acne. Some dermatoses present with
      acne-like patterns. They can be induced or perpetuated by non physiological
      factors. Among these factors, medicines must always be considered, taken either
      topically (dermocorticoids, sulfur, anti-acneic topics) or generally (androgens,
      oral corticoids, ACTH, anti-epileptics, anti-depressive drugs, anti-tuberculosis
      medications). Halogens (iodine, bromine) found in inhaled or orally taken
      pharmaceutical products, or associated with occupational contact, can also induce
      acne. Acne of exogenous origin has been described in some specific occupations,
      and are induced by exposure to chlorine, industrial oils, tar. Sun exposure, PUVA
      therapy and ionizing radiation are potentially acneigenous. Finally acne caused
      by cosmetics includes acne cosmetica, brilliantine and oily creams acne and
      detergent acne.

PMID- 12053791
TI  - [General antibiotic therapy in acne].
AB  - The primary indication for systemic antibiotics is acute therapy for moderate-to
      severe inflammatory acne. The preferred agents include tetracyclines and
      derivatives; macrolides, co-trimoxazole, and trimethoprim may represent
      acceptable alternatives. Antibiotics act mainly on inflammatory lesions (papules
      and pustules) and are only slightly comedolytic. Oral antibiotics reduce the
      number of Propionibacterium acnes. In addition, they have an anti-inflammatory
      activity. The side effects associated with oral antibiotics for acne depend on
      the drug; however, severe side effects are not common. Resistant strains of
      Propionibacterium acnes to antibiotics are increasing. Thus, general guidelines
      are useful when utilizing oral antibiotic therapy in acne.

PMID- 12053792
TI  - [Treatment of acne by isotretinoin (general course)].
AB  - Acne is a chronic disease which evolves under periodic eruptions. Resolution
      occurs around the late teens. Conventional treatment clears the lesions, but
      treatment by isotretinoin alone can achieve long remissions indeed definitive
      clearing. Indications are nodulo-cystic acne and resistant acne to a conventional
      treatment of at least 3 months duration. This drug is prescribed in cures, a cure
      is the period during which the patient receives a continuous treatment. The daily
      dose is computed according to the patient's weight and varies between 0.5 and 1
      mg/kg. To prevent relapses, it is recommended to cumulate a dose between 100 and
      150 mg/kg. No other topical or systemic treatment is needed. Side effects exist,
      among which teratogenicity is the most severe. Very strict contraception is
      necessary for women of child-bearing age. The most important mucocutaneous side
      effect is dryness and has to be counteracted by emollients. It is recommended
      that the drug be prescribed by doctors having a fair experience of oral retinoids
      and a perfect understanding of the teratogenic risk of the drug.

PMID- 12053793
TI  - [Acne and hormones].
AB  - Androgens stimulate sebum production which is necessary for the development of
      acne. Acne in women may thus be considered as a manifestation of cutaneous
      androgenization. Most of acnes may be related to an idiopathic skin
      hyperandrogenism due to in situ enzyme activity and androgen receptor
      hypersensitivity, as also noted in idiopathic hirsutism. Some acne may correspond
      to elevated ovarian or adrenal androgen secretion. The presence of acne in women
      may lead to a diagnosis of functional hyperandrogenism, either polycysticovary
      syndrome or nonclassical 21-hydroxylase deficiency. Plasma level assays for
      testosterone, delta 4 androstenedione and 17-OH progesterone and ovarian
      echography are necessary to determine the possibility for an ovarian or adrenal
      hyperandrogenism, but not to better treat acne. The goal of hormonal therapy in
      acne is to oppose the effects of androgens on the sebaceous gland. Hormones may
      be used in female acne in the absence of endocrine abnormalities. Antiandrogens
      (cyproterone acetate or aldactone) may be useful in severe acne, hormonal
      contraceptives with cyproterone acetate or non androgenic progestins in mild or
      common acne often in association with other anti-acneic drugs. Glucocorticoids
      have to be administered in acne fulminans and other forms of acute, severe,
      inflammatory acne, for their anti-inflammatory properties.

PMID- 12053794
TI  - [Topical treatment of acne].
AB  - The topical treatment of acne has a great place in the therapeutic range of
      products which is available. It can be prescribed alone in moderate acne in most
      of cases, or in combination with an oral treatment in diffuse or severe acne.
      Last years formulations have improved with a better penetration and tolerance and
      therefore a better compliance and efficiency. Also, the association of 2 active
      molecules gives better efficiency and an easier following of the treatment.
      Topical treatment can be prescribed with a cosmetic cream specially adapted for
      greasy or acneic skin which can reduce irritation and give comfort.

PMID- 12053796
TI  - [Interns and residents: French-American data].

PMID- 12053795
TI  - [Cosmetic treatments and acne].
AB  - Cosmetic products contribute to the efficacy of anti-acneic treatment. Cleaning
      bars without soap and lotions are to be preferred to soaps. Morning application
      of moisturizing creams compensate for dryness and irritation induced by topical
      treatment. Some of these cosmetic products may have a limited efficacy of the
      shiny appearance and/or acne lesions. Scrubs, abrasive sponges, masks and patches
      have a very limited usefulness. Make up and camouflage techniques are authorized,
      provided that the products have been tested non comedogenic and non acne-genic.

PMID- 12053797
TI  - [Stomach tumors].

PMID- 12053799
TI  - [Eosinophilia. Diagnostic approach].

PMID- 12053798
TI  - [Prevention of tetanus].

PMID- 12053800
TI  - [Fractures of the inferior end of the radius in adults].

PMID- 12053801
TI  - [Delay in height-weight growth].

PMID- 12053802
TI  - [Confusional state and disturbances of conscience].

PMID- 12053803
TI  - [Kidney tumors].

PMID- 12053804
TI  - [Acute ischemia of the limbs].

PMID- 12053805
TI  - [Stem cells: perspectives on their clinical application].

PMID- 12053806
TI  - [To what extent does a diet varying in calcium influence recurrent lithiasis in
      idiopathic hypercalciuria?].

PMID- 12053807
TI  - [Antibiotic-resistant fecal Escherichia coli in healthy children. Induced by the
      use of antibiotics?].
AB  - OBJECTIVE: To determine the rate of antibiotic resistance of fecal E. coli from
      healthy children and to infer if it is acquired environmentally or induced by
      antibiotic use. MATERIAL AND METHODS: Cross sectional study in children from
      schools and day care centers in Leon, Mexico. Prior antibiotic use (60 days) was
      questioned to the parents. A single fecal sample was cultured and an isolated
      colony suggestive of E. coli was submitted to biochemical identification and
      testing of disk susceptibility to 12 antibiotics. RESULTS: Four hundred fifty-six
      isolates were studied from children of 10 institutions, with ages ranging from 3
      to 72 months (mean, 42.41). Use of antibiotics was referred in 242 children
      (53.07%). The antibiotics more commonly used were trimethoprim/sulfa, ampicillin,
      and penicillin (34, 20.5, and 18%). The highest rate of resistance was found for
      tetracycline, ampicillin, and trimethoprim/sulfa (64.4, 52.63, and 46.05%). The
      resistance to ciprofloxacin, amikacin, gentamicin, and ceftriaxone was less than
      5%. Resistance to five or more antimicrobials was found in 93 isolates (20.39%);
      this rate was higher in isolates from children who received antibiotics (59/242,
      24.38% vs. 34/214, 15.89%) (p = .025; OR 1.71, IC 95% 1.04-2.81). CONCLUSIONS:
      The study suggests that saprophyte bacteria acquires resistance through both, use
      of antibiotics and from the environment. These results support the concept that
      antimicrobial resistance must be considered as a public health problem.

PMID- 12053808
TI  - [Phylogenetic distance between Giardia intestinalis isolates from symptomatic and
      asymptomatic children].
AB  - The purpose of the present investigation, was to analyze the sequences of 16S
      ribosomal genes partially amplified from 17 isolated Giardia intestinalis
      obtained from faces of 13 children with intestinal pathology and four symptoms
      free children with intestinal pathology. Analysis was made also with Giardia
      Portland-I and four Giardias isolated from dogs. Children ages in both groups
      ranged from six to twelve years. Genomic DNA was isolated using the phenol
      chloroform-isoamyl alcohol technique, and partial amplification of 16S rRNA
      ribosomal gene was carried out by the Polymerase Chain Reaction. Sequences of
      rDNA were compared with Portland-I by using CLUSTAL-W (1.81) and PHYLIP (3.6)
      software in order to determine phylogenic associations. Our results showed that
      only one isolate from symptoms-free children and three from the symptomatic
      children were associated with Portland I. The other isolated Giardias were
      associated between them and with two samples obtained from dogs that are
      phylogenetically distant from Portland-I. Two isolates from dog constituted a
      different group. These results suggest a zoonotic infection and presence of
      symptoms in children from the present investigation; probably it was associated
      with host or special characteristics of Giardia strains. The last two situations
      have a special epidemiological and public health interest.

PMID- 12053809
TI  - [Surgical treatment of lower digestive tract hemorrhage. Experience at the
      Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran].
AB  - BACKGROUND: Lower gastrointestinal bleeding is usually self-limiting in about 80%
      of cases; however, surgical treatment may be required in selected cases.
      Preoperative precise identification of the bleeding source is crucial for a
      successful outcome. OBJECTIVE: To determine the most frequent diagnoses, as well
      as short and long-term results in a series of patients who underwent a surgical
      procedure for lower gastrointestinal bleeding. MATERIAL AND METHODS:
      Retrospective analysis of 39 patients operated upon for lower gastrointestinal
      bleeding from 1979 through 1997 in a referral center. Demographic data, history,
      physical examination, laboratory tests, resuscitative measures, preoperative work
      up for identification of bleeding source, definitive cause of bleeding, surgical
      procedure, operative morbidity and mortality, as well as long-term status and
      recurrence of bleeding were recorded. RESULTS: There were 54% women and 46% men.
      Mean age was 56 years (range, 15-92). Most patients presented hematochezia (69%).
      Colonoscopy was the most used diagnostic procedure (69%). The bleeding source was
      located in 90% of patients. Diverticular disease was the most frequent cause of
      bleeding. A segmental bowel resection was the treatment in 97% of cases.
      Morbidity was 23% with 18% of mortality. Recurrence occurred in 9% of survivors.
      CONCLUSIONS: Morbidity and mortality were high. Patients who require a surgical
      operation should be carefully selected and evaluated with a complete work-up to
      determine the site and cause of bleeding.

PMID- 12053810
TI  - [Risk factors associated with bronchiolitis in children under 2 years of age].
AB  - INTRODUCTION: The objective of this study was to determine the risk factors
      associated to bronchiolitis in infants less than two years of age. MATERIALS AND
      METHODS: Prospective case-control study was performed in a hospital of second
      level of attention. The sample size was calculated for a level of confidence of
      95%, a power of 90%, and a difference of exposure of 15% between cases and
      controls. For each case, there was one control matched for age and sex. The cases
      were obtained in the pediatric emergency room and the controls were healthy
      infants who came to the preventive medicine service of the same hospital. The
      diagnosis of bronchiolitis was established by direct observation in accordance to
      clinical criteria and chest X-ray. All the patients were weighed to the moment to
      be included in the study, and through structured interview the following
      variables were investigated: family history of bronchial asthma and atopy in
      immediate family members, prematurity, mechanical ventilation, bronchopulmonary
      dysplasia, present-day breast-feeding, length of time of breast feeding, early
      weaning, passive tobacco smoke exposure, maternal smoking, housing and living
      with domestic animals. The global significance of the study was probed by
      multiple logistic regression. RESULTS: Were studied 110 pairs with a range of age
      of 10 days to 23 months (average of 7.1 +/- 4.7 months), 49 pairs were female and
      61 male (ratio 1:1.2) The variables significantly associated (P < or = 0.05) to
      bronchiolitis were family history of bronchial asthma in immediate family members
      (OR: 2.9, IC 95% 1.29-6.34) and prematurity (OR: 3.0, IC 95% 1.04-8.87). The
      early weaning(OR: 0.44, IC 95% 0.24-0.79) and present-day breast-feeding (OR:
      0.53, IC 95% 0.30-0.95) revealed a significant negative association. The other
      studied variables didn't show statistically significant association with
      bronchiolitis. CONCLUSIONS: Factors that increase the risk of bronchiolitis are a
      history of prematurity, and family history of bronchial asthma. Factors that have
      a protective effect are early weaning, and present-day breast-feeding.

PMID- 12053811
TI  - Cortical, brainstem and autonomic nervous system dysfunction in infants with post
      hemorrhagic hydrocephalus.
AB  - OBJECTIVE: The aim of this study was to evaluate the degree of central and
      autonomic dysfunction by means of electroencephalographic (EEG) and cardio
      pneumographic recording (CPGR) in infants with Post-Hemorrhagic Hydrocephalus
      (PHH). METHODS: Nineteen infants with PHH were studied, born from October 1998 to
      January 2000. Clinical diagnosis was confirmed by cephalic perimeter measurement
      and ultrasonographic study. Eight channel bipolar EEG and CPGR were performed
      after sleep deprivation, EEG features studied were: Temporal organization,
      symmetry, synchrony, frequency of normal and abnormal patterns. CPGR features
      studied were: Frequency of apnea and temporal organization by means of beat to
      beat variability. RESULTS: Averages of birth's age and weight, Apgar scores at
      one and five minutes, and cephalic perimeter showed lower values in PHH infants.
      PHH infants showed abnormalities in EEG and CPGR such as: Higher discontinuous
      activity (63%), asymmetry (73%), asynchrony (89%), abnormal EEG patterns (89%),
      apnea (26%) and absence of heart rate variability (63%). CONCLUSIONS: EEG and
      CPGR recordings are a useful tools in the examination of infants with PHH. These
      findings suggest cortical-subcortical, and brainstem dysfunction with severe
      encephalopathy and autonomic nervous dysfunction related to ventricular
      dilatation in infants with PHH.

PMID- 12053812
TI  - [Analysis of liver biopsy experience in a regional hospital].
AB  - Hepatic biopsy is a safe procedure. Its findings contribute to precise diagnoses
      and in selecting or modifying the treatment of some patients with liver diseases.
      AIM: To analyze indications, findings and complications of hepatic biopsy.
      MATERIAL AND METHODS: Retrospective study of patients with hepatic disease in
      which a hepatic biopsy was obtained. Information pertaining to clinical
      characteristics, biopsy indications and its results were collected. All tissue
      samples were stained with hematoxylin-eosin, Masson and Perl. The analysis was
      performed by descriptive statistics, chi 2 test and the Fisher exact test.
      RESULTS: There were 54.6% were women and 45.4% were men. In 361 patients the
      major diagnoses were: Hepatic cirrhosis 19.1%, hepatic metastases 16.3%, chronic
      hepatitis 11.6%, alcoholic hepatitis 11.1% and nonalcoholic steatohepatitis 9.7%.
      In 66.2% of the biopsies were preformed meanwhile patients were in the Hospital.
      The procedure was ultrasound-assisted in 76%. There were major complications in
      1.4%. CONCLUSION: The hepatic disease is more common in the woman and the
      pathologic results show that the etiology of liver diseases in our hospital are
      similar to reports of third level hospitals in Mexico, its major complications
      were fewer.

PMID- 12053813
TI  - [Mechanism of action of sterol regulatory element binding proteins (SREBPs) in
      cholesterol and fatty-acid biosynthesis].
AB  - Cholesterol is an important lipid in higher organisms, and its concentration must
      be maintained in narrow limits depending of the cell needs. An excess of dietary
      cholesterol can lead to serious health problems, however, if consumption of this
      lipid is restricted in the diet, cells have the capacity to synthesize it. For
      the synthesis of cholesterol, the cell uses a family of proteins named sterol
      regulatory element binding proteins (SREBP's), that are transcriptional factors
      involved in the control of expression of genes of cholesterol and fatty acids
      synthesis. SREBP's regulate gene transcription by binding to cis-acting elements
      denominated sterol regulatory elements (SRE-1). SREBP's are localized in the
      endoplasmic reticulum, but in the event that the cell needs to synthesize
      cholesterol, the NH2-terminal portion of these proteins is cleaved by two
      specific proteases, and then travels into the nucleus to function as
      transcriptional factor. The present review shows the details of the mechanism
      that the cell uses to regulate cholesterol biosynthesis by the SREBP's, and its
      potential metabolic implications.

PMID- 12053814
TI  - [Graft vs. tumor effect in chronic granulocytic leukemia].

PMID- 12053815
TI  - [Leptin].
AB  - Leptin is a hormone secreted by adipocytes, stomach and placenta. Age, sex,
      puberty onset and food intake are the most important physiological factors that
      determines leptin concentration. It has been shown that leptin secretion is
      regulated by other hormones such as insulin, glucocorticoids and sex steroids.
      Leptin has an important role in hungry and satiety regulation as well as in
      normal sexual maturation. There have been some studies in obese subjects showing
      promising results with leptin administration.

PMID- 12053816
TI  - [Effect of menopause on the activity of systemic lupus erythematosus].

PMID- 12053817
TI  - [Those die who have to die].

PMID- 12053818
TI  - [Pontine myelinolysis after a hypoglycemic episode].
AB  - A case of central pontine myelinolysis following hypoglycemia is reported. The
      case was a 26- year-old female. Diabetes mellitus was found when she was 8 years
      old and she has hypertension and renal failure. She suffered a severe
      hypoglycemia at an unknown time. After the episode she developed a vegetative
      state. A magnetic resonance scan showed features consistent with the presence of
      central pontine myelinolysis.

PMID- 12053819
TI  - Medication decisions--right and wrong.
AB  - This paper reviews the recent literature on problems associated with prescription
      drug use in older adults. The authors address four major issues: Why giving
      patients the wrong drug is so common; how taking the wrong amount is an even
      larger problem; why good drugs may be wrong for particular patients; and how high
      out-of-pocket spending and inadequate insurance coverage may disrupt otherwise
      sound drug regimens. The organizing theme of this review is the right drug for
      the right patient, taken in the right way at the right price. Despite significant
      gaps in the research record the evidence leaves no doubt that elderly individuals
      are at significant risk for inappropriate medication use. The paper concludes
      with an agenda for future studies: the need to validate standards for geriatric
      drug use, assess inappropriate drug use at the national level, establish
      population-based risk factors, and target research to the most significant
      adverse outcomes.

PMID- 12053820
TI  - Health insurance and family structure: the case of adolescents in skipped
      generation families.
AB  - Since 1970, both the number and proportion of children being parented by a
      grandparent without the help of a parent has increased substantially. The
      increase in skipped-generation households has generated much concern from policy
      makers because such households are, on average, disadvantaged compared with most
      other household types. One important challenge facing grandparents with parenting
      responsibilities is securing health insurance for their dependent grandchildren.
      In this study, the authors investigate the extent to which grandparents raising
      their grandchildren were able to secure health insurance for their dependent
      grandchildren. They find that adolescents living in skipped-generation families
      in 1995 were more often uninsured, more often publicly insured, and less often
      privately insured compared with adolescents in other family types. Even after
      controlling for income, work status, and education, adolescents in skipped
      generation families were still more likely to have public insurance and less
      likely to have private insurance compared with other adolescents.

PMID- 12053821
TI  - Children in the Oregon Health Plan: how have they fared?
AB  - This study examines the impact of the Oregon Health Plan (OHP) on children's
      access to care. A telephone survey was conducted in 1998 of two groups of
      children: OHP enrollees and food stamp recipients not enrolled in OHP. Much of
      OHP's impact has been realized by the simple extension of health insurance
      coverage to Oregon's low-income children. The availability of insurance
      significantly increased the use of physician visits and dental care. The priority
      list had little effect on children, affecting only 2 percent of OHP children
      surveyed, most of whom succeeded in getting the service anyway. Thus, despite the
      negative publicity prior to its implementation, there is no evidence that
      "rationing" under OHP has substantially restricted access to needed services for
      children.

PMID- 12053822
TI  - Measuring deception: test-retest reliability of physicians' self-reported
      manipulation of reimbursement rules for patients.
AB  - This study examined the test-retest reliability of physicians' self-reported
      manipulation of reimbursement rules for patients. The test-retest reliability of
      self-report of three specific tactics were examined: (1) exaggerating the
      severity of patients' conditions, (2) changing a patient's official (billing)
      diagnosis, and (3) reporting signs or symptoms that patients did not have. The
      reliability of a scaled summary measure of physicians' manipulation of
      reimbursement rules was also assessed. Overall, the authors found high levels of
      test-retest agreement across all three items and the summary measure. These
      findings suggest that self-report can be used to produce reliable data on this
      controversial issue. Specifically, the three items reported here can be used to
      produce a reliable summary measure of physicians' manipulation of reimbursement
      rules to help patients obtain care that physicians perceive as necessary.

PMID- 12053823
TI  - Nursing staff reductions in Pennsylvania hospitals: exploring the discrepancy
      between perceptions and data.
AB  - Previous research has not confirmed public and practitioner perceptions of a
      decline in hospital nurse staffing. One reason for this discrepancy is that
      aggregate or mean values may not be an accurate description of the situation in a
      sizable percentage of hospitals. This article calculates the mean percentage
      change in various measures of nursing staff in Pennsylvania hospitals, 1991-1997,
      and the percentage of hospitals that experienced various degrees of this change.
      Major findings are that the means of changes in nursing staff understate the
      declines. When adjusted for patient severity and outpatient care, 50 percent of
      the hospitals experienced large decreases in RNs per patient days of care, 70
      percent had large decreases in LPNs per patient days of care, and 56 percent had
      large declines in licensed nurses per patient days of care. Overall, the findings
      support perceptions of a decline in licensed nurse staffing. Policy implications
      are discussed.

PMID- 12053824
TI  - [Attention deficit hyperactivity disorder in children].

PMID- 12053825
TI  - [New treatments for psoriasis].

PMID- 12053826
TI  - [Polypathology in geriatric patients and dosage adjustments].

PMID- 12053827
TI  - [Sun and drugs].

PMID- 12053828
TI  - Managing solar keratoses.
AB  - Solar keratoses (actinic keratoses) are common, often multiple, epidermal lesions
      found mainly on the sun-exposed skin of fair-skinned middle-aged and older
      people. They may transform into non-melanoma skin cancers, particularly squamous
      cell carcinoma. Here, we review the prevention and treatment of solar keratoses.

PMID- 12053829
TI  - What to do about traveller's diarrhoea.
AB  - Traveller's diarrhoea is common but usually mild and self-limiting. However, it
      can disrupt business plans or spoil a holiday. Here, we discuss its prevention
      and treatment, and the investigation of patients whose symptoms persist after
      returning home.

PMID- 12053830
TI  - MS, Parkinson's disease and physiotherapy.
AB  - In the UK, around 10-12 in every 10,000 people have multiple sclerosis, typical
      features of which include weakness, ataxia, spasticity and sensory loss. By
      comparison, around 16-18 in every 10,000 have Parkinson's disease, a condition
      typified by rigidity, bradykinesia, tremor and postural instability. Both
      conditions can limit function with, for example, nearly 25% of patients with
      multiple sclerosis and about 10% of those with Parkinson's disease being
      dependent on a wheelchair. Physiotherapy is widely used as part of a
      multidisciplinary approach to the management of multiple sclerosis, while 7-38%
      of people with Parkinson's disease are referred for physiotherapy. Here, we
      review the evidence for physiotherapy in the management of patients with either
      condition.

PMID- 12053831
TI  - Acute renal failure in the critically ill patient.
AB  - This article focuses on the epidemiology, pathogenesis, and prevention of the
      most common forms of acute renal failure encountered in the critically ill. These
      include pre-renal azotemia and acute tubular necrosis that occurs
      postoperatively, in patients with rhabdomyolysis, or as a complication of sepsis.
      In addition, some unusual causes of acute renal failure that occur predominantly
      in the intensive care unit are briefly discussed.

PMID- 12053832
TI  - Dialysis modalities in the intensive care unit.
AB  - Acute renal failure in the ICU is a clinically diverse entity. Consequently, the
      indications for initiation of dialysis therapy are varied. In general, the
      indications are solute control, volume control, or both. A variety of dialysis
      modalities are available; however, there is no consensus as to the optimal
      modality for any particular group of patients. A careful understanding of the
      particular benefits, limitations, and potential complications of each modality
      coupled with a thorough assessment of the individual patient's need formulate the
      basis for dialysis modality selection. In certain circumstances, the more
      conventional intermittent therapies are sufficient, whereas in other settings,
      CRRT techniques are advantageous. The impact of modality selection on outcome
      remains an area of significant controversy. Future studies in which more
      uniformity within specific subgroups of patients with ARF is sought may shed
      light on the optimal modality for a particular patient group. Newer therapies
      aimed at more optimal and more specific blood purification may prove promising in
      the management of complex critically ill patients with ARF and other comorbid
      conditions.

PMID- 12053833
TI  - Clinical approach to disorders of salt and water balance. Emphasis on integrative
      physiology.
AB  - Our purpose was to illustrate the utility of an approach that begins with simple
      principles of physiology to patients who have a disturbance in salt and water
      balance (Table 1). At times, the physiology is restricted to the kidney and body
      fluid compartments. In these settings, the goals of therapy are defined by
      calculating a tonicity balance--electrolyte-free water balances simply do not
      provide the needed information [3]. At other times, performing balances of other
      solutes such as urea reveal that another critically important problem is present
      (tissue catabolism). Thus the physiologic analysis becomes more integrative,
      extending beyond renal issues. Goals for therapy become clearer once the
      integrative physiology is known. More modern contributions from molecular studies
      permit a revised interpretation of the physiology. An example presented was the
      possible role of gentamicin-like drugs as a cause of high output renal failure
      that is basically a persistent loop diuretic-like effect. In the patient
      presenting with hyponatremia, the first step is to determine if the time course
      is less than 48-hours because emergency therapy is different in this setting.
      With acute hyponatremia, the objective is to diminish brain cell swelling
      especially if even mild symptoms are present. In contrast, the objective in the
      patient with chronic hyponatremia is to prevent ODS. An even slower rate of rise
      of the PNa is required in patients who are malnourished and/or K+ depleted.

PMID- 12053834
TI  - Disorders of potassium homeostasis. Hypokalemia and hyperkalemia.
AB  - This article reviews the diagnosis and management of clinical disorders of
      potassium balance, with particular attention to the critically ill patient. The
      normal regulation of potassium balance is reviewed as a background for
      understanding these disorders, followed by a discussion of the causes and
      management of hypo- and hyperkalemia. Practical guidelines are presented for
      acute and chronic management.

PMID- 12053835
TI  - Metabolic acidosis in the intensive care unit.
AB  - Metabolic acidosis is a common occurrence in critically ill patients.
      Understanding the pathological mechanisms underlying the generation of protons
      will enable the clinician to quickly recognize these disorders and establish an
      acceptable treatment strategy. This article presents a logical approach to
      metabolic acidosis.

PMID- 12053836
TI  - Thrombotic microangiopathies.
AB  - The thrombotic microangiopathies (TMA) are a group of diseases associated with
      microangiopathic hemolytic anemia, thrombocytopenia, and end-organ dysfunction.
      These seemingly disparate entities share in common a pathogenic mechanism
      involving endothelial injury and thrombus formation. Prognosis and treatment
      depend on the nature of the underlying disease.

PMID- 12053837
TI  - Evaluation and treatment of vasculitis in the critically ill patient.
AB  - The systemic vasculitides, if left untreated, often lead to major organ damage
      and death. When a patient presents with features that may be consistent with
      vasculitis, especially with pulmonary and renal findings, it is important to make
      a specific diagnosis as quickly as possible so that specific therapy can be
      started. Diagnosis is dependent on familiarity with the myriad of typical and
      unusual clinical features of the various vasculitides together with performance
      of supportive tests including serologies, angiograms, and biopsies. When
      evaluating a potential case of vasculitis, clinicians must comprehensively search
      for other more common, non-vasculitic diseases. The diagnosis may be even more
      difficult in patients with established diagnoses of vasculitis on
      immunosuppressive treatment who develop new clinical findings. Rapid initiation
      of immunosuppressive therapy for critically ill patients with vasculitis is
      crucial and may be life-saving.

PMID- 12053838
TI  - Hepatorenal syndrome. Definition, pathophysiology, and intervention.
AB  - Hepatorenal syndrome is a well characterized entity in which vasodilation of
      splanchnic vessels and intense constriction of the renal cortical vasculature
      occur in concert. The condition is often fatal unless orthotopic liver
      transplantation (OLT) is performed. Many extracorporeal blood purification
      techniques exist which can be offered to patients awaiting OLT. Continuous
      hemofiltration, with or without other modalities such as therapeutic plasma
      exchange and hemoperfusion, may be helpful in improving the level of
      consciousness of these patients. Unfortunately, mortality and hepatic
      regeneration do not appear to be affected by such interventions. The development
      of a hybrid bioartifical liver support system and pharmacologic manipulation of
      the hemodynamic perturbations that occur in HRS provide particularly appealing
      prospects as a means of providing a bridge to liver transplantation in the
      future.

PMID- 12053839
TI  - Plasmapheresis. Technical aspects and indications.
AB  - In summary, use of plasmapheresis has changed in recent years given advances in
      medical technology that have allowed a wider clinical application in the critical
      care setting. Membrane filtration technology has provided an alternative to
      centrifugation that can be easily applied in intensive care units. Use of
      plasmapheresis has also changed in recent years reflecting the availability of
      evidence largely obtained from controlled prospective studies. However, the
      clinical efficacy of plasmapheresis for many acute renal conditions is still
      controversial. Plasmapheresis appears to be a useful adjunct to conventional
      therapy in the treatment of anti-GBM nephritis, severe dialysis-dependent forms
      of pauciimmune RPGN, cryoglobulinemia, and HUS-TTP. Reported data also suggest a
      possible benefit of plasmapheresis in patients with myeloma cast nephropathy,
      sepsis, and poisoning/overdose, but the case for plasmapheresis in these
      disorders is largely unproven and the reported evidence insufficient to recommend
      its use outside research settings. In contrast, data from controlled trials do
      not support a role for plasmapheresis in immune complex-mediated RPGN, such as
      lupus nephritis, and acute allograft rejection. The more widespread application
      of prospective, randomized, controlled clinical trials should help to better
      define the value of plasmapheresis for treatment of acute renal diseases.

PMID- 12053840
TI  - Extracorporeal therapies for acute intoxications.
AB  - Intoxications frequently perturb acid-base and electrolyte status, intravascular
      volume, and renal function. In selected cases, extracorporeal techniques
      effectively restore homeostasis and augment intoxicant removal. The use of 4
      methylpyrazole, an inhibitor of alcohol dehydrogenase, is a new and effective
      treatment for patients exposed to toxic alcohols. In this section, practical
      approaches to commonly encountered intoxicants and the use of extracorporeal
      techniques are critically reviewed.

PMID- 12053841
TI  - Critical care issues in the patient with chronic renal failure.
AB  - The metabolic abnormalities associated with chronic renal failure and
      complications of the dialysis procedure present unique challenges in critical
      care medicine. Understanding how renal failure impacts the development and
      management of cardiovascular disease, bleeding tendencies, infection, and
      malnutrition is necessary to provide optimal care for these patients. The
      recognition of ESRD as a state of chronic inflammation and increased oxidative
      stress ultimately should lead to more effective treatment approaches for several
      of the comorbid conditions common in this patient population.

PMID- 12053842
TI  - The role of state government, local government, and nongovernmental organizations
      in medical innovative readiness training.
AB  - This article describes the Medical Innovative Readiness Training program of the
      Wisconsin Army National Guard. State government coordinates the various entities
      involved, and local government does most of the planning for the actual medical
      care that will be rendered. Funding is through the National Guard Bureau. The
      bulk of the medical professional manpower comes from National Guard medical
      units.

PMID- 12053843
TI  - Primary care enrollment levels in staff- and group-model health maintenance
      organizations: a standard to compare military enrollment with civilian
      organizations.
AB  - A literature review was conducted to determine civilian staff- and group-model
      health maintenance organization (HMO) primary care provider staffing. Civilian
      staff- and group-model HMOs enroll an average of 1,473 members per primary care
      physician. When physician extenders are considered, the average enrollment is
      1,156 members per primary care provider. Despite the similarities between the
      staff- and group-model HMO and military medicine, military medical care is
      significantly different and may decrease the capability for enrollment as a
      result of mission support, occupational medicine, and other military-unique
      factors. Comparisons between military and civilian enrollment should be tempered
      with these considerations.

PMID- 12053844
TI  - Differentiation of the health behavior patterns related to prostate cancer
      screening among African-American men in military settings.
AB  - The objectives of this study were to identify, describe, classify, and
      differentiate African-American men (AAM) in military settings according to the
      frequency with which they regularly, infrequently, or did not screen for prostate
      cancer using factors of the Health Belief Model. Participants in the study
      included 147 military health care beneficiaries who were AAM 40 years of age and
      older. Self-reporting questionnaires were used to collect data pertaining to the
      objectives. The results revealed that 85% of the men reported having screened for
      prostate cancer and more than 54% of them reported screening "annually."
      Discriminant analysis statistics revealed that age, education, and "perceived
      benefits" of the digital rectal examination and the prostate-specific antigen
      test best differentiated AAM who screened annually compared with nonscreeners.
      Educating AAM on the benefits and efficacy of the digital rectal examination and
      prostate-specific antigen tests may be helpful in increasing screening practices
      in this high-risk group.

PMID- 12053845
TI  - Drug-positive rates for the Army from fiscal years 1991 to 2000 and for the
      National Guard from Fiscal years 1997 to 2000.
AB  - This article examines the positive rate by drug for all urinalysis specimens
      tested by the U.S. Army from fiscal year 1991 (FY91) to FY00 and for the Army
      National Guard (NG) from FY97 to FY00. The average positive rate for the Army
      from FY91 to FY00 was 0.84%. In FY00, the Army rate reached a 10-year high of
      1.04%. From FY97 to FY00, the NG positive rate declined from 3.4% to 2.16% but
      was significantly (p < 0.05) higher than the Army rate during the same period.
      Marijuana and cocaine are the most abused drugs for both the Army and NG. The
      positive rate for marijuana in the Army from FY91 to FY00 was 0.51%, and the
      cocaine rate was 0.19%. The NG marijuana-positive rate from FY97 to FY00 was
      1.70%, and the cocaine rate was 0.51%. The positive rate for all other drugs of
      abuse tested was less than 0.3% for both the Army and NG during the same periods.
      The overall positive rate for the Army and NG are below those estimated (6.3%) in
      the civilian population.

PMID- 12053846
TI  - Foot evaluation by infrared imaging.
AB  - For better assessment of foot injury severity during basic military training, we
      evaluated a simple noninvasive technique: thermography. With this infrared
      imaging method, we determined normal foot parameters (from 30 soldiers before
      training), thermographic findings in different foot stress fractures (from 30
      soldiers so diagnosed), and normal responses to abnormal stresses in 30 trainees
      who underwent the same training as the previous group but did not have
      musculoskeletal complaints. We found that normal foot thermograms show onion peel
      like progressive cooling on the plantar surface, with a medially located warm
      center at the instep. Thermograms of injured feet show areas of increased heat,
      but excessive weight-bearing pressures on feet, new shoes, or boots also cause
      increased infrared emission even without discomfort. Differentiation remains
      difficult; however, thermography can detect injury early. It does not reveal
      exact diagnoses, but its greatest benefit is easy follow-up to monitor severity
      and healing.

PMID- 12053848
TI  - Clearing the cervical spine in victims of blunt trauma.
AB  - Cervical spine injuries occur in 2.3% to 6.4% of victims of blunt trauma. The
      difficulty of identifying the minority of patients with cervical spine injuries
      continues to challenge those who triage and treat the acutely injured. We
      retrospectively reviewed our practice for cervical spine clearance, which
      consists of three-view plain radiographs supplemented by focused further studies,
      such as computed or plain film tomography and flexion/extension views, as needed.
      Fifty-four patients with cervical spine injuries were identified during a 39
      month period, which represented approximately 1% of the patients evaluated.
      Eighty cervical spine injuries were found, of which nine were missed. Review of
      the six patients in whom the nine cervical spine injuries were missed
      demonstrated error in the interpretation of radiographic studies in five
      patients, only two of whom were felt to have technically adequate films in
      hindsight. We conclude that a protocol based on three-view plain film radiographs
      supplemented by focused additional studies will allow the visualization of
      virtually all cervical spine injuries and that the main cause of missed injuries
      is errors of interpretation.

PMID- 12053847
TI  - Costs of excess body weight among active duty personnel, U.S. Air Force, 1997.
AB  - Although the increasing public health impact of excess body weight in the U.S.
      general population has received national attention, the impact of excess body
      weight among active duty military personnel is unknown. A study was conducted to
      determine the direct (increased medical care) and indirect (lost workdays) costs
      of excess body weight among active duty Air Force (ADAF) personnel in 1997. Based
      on measured height and weight values, in 1997, 20.4% of ADAF men and 20.5% of
      ADAF women had body weights that exceeded their official maximum allowable weight
      for height. Total excess body weight-attributable costs were estimated at $22.8
      million per year, with annual direct and indirect costs estimated at $19.3
      million (approximately 6% of total annual expenditures for ADAF medical care) and
      $3.5 million, respectively. Attributable lost workdays were estimated at 28,351
      per year. Annual excess body weight-attributable costs among ADAF personnel are
      high, both in dollars and lost duty days.

PMID- 12053849
TI  - Determining the level of job satisfaction of nurses working at Turkish military
      forces hospitals.
AB  - The purpose of this study was to determine the level of job satisfaction of
      nurses working at Turkish military hospitals. A questionnaire was prepared as a
      data-gathering tool. This study measured the job satisfaction level at two
      stages. At the first stage, nurses' expectations for their jobs were measured
      with a Likert-type scale; at the second stage, the current level of satisfaction
      was determined. The differences between expectations and current level of
      satisfaction was calculated as the level of job satisfaction.

PMID- 12053850
TI  - Women in the Persian Gulf: lack of gender differences in long-term health effects
      of service in United Kingdom Armed Forces in the 1991 Persian Gulf War.
AB  - A cross-sectional postal survey was conducted to evaluate the health of a random
      sample of United Kingdom Armed Forces personnel who were deployed to the 1990
      1991 Persian Gulf conflict compared with nondeployed controls and controls
      deployed to Bosnia. The health of service women was examined and compared with
      that of United Kingdom service men. The main outcome measures were physical
      symptoms and ailments, functional capacity on the 36-item Short-Form Health
      Survey, the 12-item General Health Questionnaire, the Centers for Disease Control
      and Prevention multisymptom criteria for Gulf War illness, and post-traumatic
      stress reactions. There were 645 (65.3%) valid responses. The women from the Gulf
      cohort reported each symptom and the majority of health outcomes more frequently
      than either control group. No gender differences were found for 32 of the 50
      symptoms assessed. Of the remaining 18 symptoms, women reported significantly
      more than men for only 6 of them, and there were no gender differences in 5 of
      the 6 principal health outcome measures. Women deployed to the Persian Gulf had
      similar rates of ill health as their male counterparts. Nothing was found to
      suggest that, other than for gender-specific health effects, any special
      considerations need to be made on health grounds for service women in any future
      deployments.

PMID- 12053851
TI  - Clinical management of Gulf War veterans with medically unexplained physical
      symptoms.
AB  - Veterans of the Persian Gulf War have increased rates of medically unexplained
      physical symptoms (MUPS). This article describes a model for the clinical
      management of MUPS in Gulf War veterans. Predisposing, precipitating, and
      perpetuating factors contribute to the emergence and clinical course of MUPS.
      Predisposing factors include biologically and psychosocially determined
      vulnerabilities that render individuals more susceptible to MUPS and related
      morbidity. Precipitating factors promote the onset of MUPS. These factors are
      triggering events that serve to initiate episodes of MUPS. Perpetuating factors
      sustain illness. They maintain, exacerbate, or prolong MUPS and associated
      distress and disability. Intervention involves identifying and addressing all
      relevant predisposing, precipitating, and perpetuating factors. A representative
      patient vignette is presented to illustrate the clinical utility of the model for
      a Gulf War veteran with MUPS.

PMID- 12053852
TI  - Military internal medicine resident performance on the American Board of Internal
      Medicine Certifying Examination.
AB  - The mission of military graduate medical education in internal medicine is to
      produce high-quality military internists prepared to practice in military
      environments. Board certification in internal medicine is an important outcome of
      internal medicine residency training. The American Board of Internal Medicine
      Certifying Examination (ABIMCE) first-taker pass rate of the graduates of an
      internal medicine residency program is a key measure of the quality of the
      program. We compared the ABIMCE first-taker pass rates for military and civilian
      internal medicine residency program graduates. Military internal medicine
      residency graduates had higher first-taker pass rates than their civilian
      counterparts. This is likely a reflection of the high-quality residents and the
      faculty at military programs. These results support the notion that military
      internal medicine residency programs continue to fulfill their mission of
      training high-quality internists.

PMID- 12053853
TI  - Access to Mental Health Services at Veterans Affairs community-based outpatient
      clinics.
AB  - Access to care and treatment of mental disorders within the Veterans Health
      Administration (VHA) has seen dramatic changes in recent years. The VHA has been
      transformed from a hospital-based provider to one that relies on more outpatient
      care, although some are concerned this has compromised specialty services such as
      mental health care. The VHA is increasing the number of community-based
      outpatient clinics, which has improved access to primary care, and some are
      suggesting providing more mental health services at these clinics. The objective
      of this survey was to determine which clinics are currently providing mental
      health care and to identify clinics that provide little or no mental health care
      and their reasons for not doing so. A questionnaire was developed to answer these
      questions, and clinics were contacted by telephone to complete the survey. The
      results indicate that more clinics are providing basic mental health services
      than has been reported previously. The results also suggest that, before making
      changes in the delivery of mental health care within the VHA, a comprehensive
      study needs to be performed to identify current needs and establish a clear goal
      of how and where to provide quality mental health care for veterans.

PMID- 12053854
TI  - Acute stress reactions after submarine accidents.
AB  - The aim of the present study was to explore contextual and individual factors
      associated with acute stress reactions in three Norwegian submarine crews exposed
      to different significant peacetime maneuver accidents. Approximately 2 to 3 weeks
      after the accidents, crew members completed the Coping Style Questionnaire, the
      General Health Questionnaire, the Impact of Event Scale, and the Post-Traumatic
      Symptom Scale. Although exposed subjects (N = 47) revealed more posttraumatic
      stress symptoms than nonexposed crew members on shore leave (N = 7), they showed
      less acute stress reactions than survivors from a surface ship accident in the
      Norwegian Navy. Inspection of individual cases revealed that 4% of the exposed
      submariners showed high loads of acute stress symptoms. Unit cohesion and
      habitual coping styles emerged as resilience factors, whereas previous exposure
      to critical incidents and personal experience of not coping in the accident
      situation emerged as vulnerability factors, explaining 32% of the acute stress
      reactions reported by submarine crew members.

PMID- 12053855
TI  - Death by water intoxication.
AB  - With recent emphasis on increased water intake during exercise for the prevention
      of dehydration and exertional heat illness, there has been an increase in cases
      of hyponatremia related to excessive water intake. This article reviews several
      recent military cases and three deaths that have occurred as a result of
      overhydration, with resultant hyponatremia and cerebral edema. All of these cases
      are associated with more than 5 L (usually 10-20 L) of water intake during a
      period of a few hours. The importance of maintaining adequate hydration in
      exertional heat illness prevention cannot be overemphasized, but excessive fluid
      intake may lead to life-threatening hyponatremia. Current guidelines provide
      safety by limiting fluid intake during times of heavy sweating to 1 to 1.5 L per
      hour.

PMID- 12053856
TI  - Fatal water intoxication of an Army trainee during urine drug testing.
AB  - An Army trainee developed acute water intoxication, hyponatremia, pulmonary
      edema, and fatal cerebral edema. This is the first report of a fatality related
      to urine drug testing. This resulted from supervised excessive water ingestion in
      an attempt to induce a sufficient urine specimen for substance abuse testing. To
      avoid a similar preventable death in the future, we make several recommendations.
      These include limiting the volume of ingested fluid to eight ounces every 30 to
      45 minutes, not to exceed 40 ounces, and providing a relaxed, reassuring
      environment when obtaining urine specimens for substance abuse detection.

PMID- 12053857
TI  - The circumferential antishock sheet.
AB  - Hemorrhage control in patients with pelvic ring disruptions remains problematic.
      To decrease bleeding, efforts have been made to acutely reduce and stabilize the
      pelvis. The goals of rapid pelvic reduction and stabilization are restoration of
      normal pelvic volume, protection of the early clot, and improved patient comfort.
      The use of military antishock trousers, hip spica casts, external fixators,
      antishock pelvic clamps, early open reduction/internal fixation, and open packing
      have been reported in the literature. A simple temporary technique of reduction
      is reported using a circumferential bed sheet. The sheet is placed between the
      iliac crests and the greater trochanters, encircling the pelvis. The
      circumferential sheet provides stabilization for transportation and allows
      transfemoral angiographic embolization or exploratory laparotomy at the receiving
      hospital. Definitive fixation can then be accomplished.

PMID- 12053858
TI  - Mary, a 4-year-old with oppositional defiant disorder.
AB  - OBJECTIVE: Examine the treatment course of a 4-year-old girl with oppositional
      defiant disorder, which developed in the context of her father's deployment to
      Bosnia. METHOD: A case report of the interventions made with this patient and her
      clinical outcomes. RESULTS: The patient's behavior improved substantially with
      regular therapy sessions and with a designated playtime with her mother.
      CONCLUSIONS: One possible cause of oppositional defiant disorder is a parent
      child attachment deficit. In this case, the child's parents are both active duty
      service members and her father was deployed overseas. Young children have
      difficulty verbalizing feelings of loss and may respond behaviorally by exerting
      control over their immediate environment. Some children may respond to
      unstructured play sessions in which they are able to express feelings and gain
      some control in their interactions with adults.

PMID- 12053859
TI  - The role of growth factors in malignancy: a focus on the epidermal growth factor
      receptor.
AB  - OBJECTIVES: To review the role of growth factors in the development of malignancy
      with a focus on the epidermal growth factor receptor (EGFR) pathways. The
      clinical significance and prognostic implications of EGFR expression in
      malignancy will be discussed in addition to screening methods used for detection
      of EGFR expression. DATA SOURCES: Research articles and textbooks. CONCLUSIONS:
      Growth factors and their receptors play an important role in the development and
      progression of malignancy. The association between the EGFR pathway and
      malignancy is well defined and many agents that block the EGFR pathways are in
      clinical testing. IMPLICATIONS FOR NURSING PRACTICE: Knowledge about the role of
      growth factors in malignancy has increased greatly over the past few decades.
      Many new biological agents targeted at growth factor pathways are in the late
      stages of clinical testing and are likely to be approved and available soon. It
      is imperative that nurses understand the underlying growth factor biology and the
      mechanisms by which targeted biological agents exert their antitumor effects, and
      be able to apply these principles in clinical practice.

PMID- 12053860
TI  - Introduction to colorectal cancer.
AB  - OBJECTIVES: To provide an overview of colorectal carcinoma (CRC), including
      current treatment strategies for various stages of the disease. DATA SOURCES:
      Research articles and textbooks. CONCLUSIONS: Despite screening methods for early
      detection of CRC, many patients present with late-stage disease and have a poor
      prognosis. The approval of irinotecan for CRC changed the approach to treatment,
      and there are numerous agents under clinical evaluation that may soon be
      available for the management of patients with CRC. IMPLICATIONS FOR NURSING
      PRACTICE: Recent advances in molecular targeting have led to the development of
      new treatments for CRC. Because nurses will ultimately administer these agents,
      it is important to understand how these agents target CRC.

PMID- 12053861
TI  - The role of the epidermal growth factor receptor in the treatment of colorectal
      carcinoma.
AB  - OBJECTIVES: To review the implications of epidermal growth factor receptor (EGFR)
      blockade and become familiar with the clinical experience in colorectal carcinoma
      to date. DATA SOURCES: Research articles and textbooks. CONCLUSIONS: Blockade of
      the EGFR results in clinically significant antitumor activities in a variety of
      tumors, including colorectal carcinoma. There are a variety of mechanisms by
      which to block the EGFR pathway. Those that have undergone extensive clinical
      testing include tyrosine kinase inhibitors and anti-EGFR monoclonal antibodies.
      In addition, biological agents have shown promise when combined with traditional
      cytotoxic approaches. IMPLICATIONS FOR NURSING PRACTICE: With many targeted
      biological agents undergoing evaluation, it is important that nurses become
      familiar with early clinical experience to understand their role in the treatment
      of cancer.

PMID- 12053863
TI  - For Oklahoma BMET, computer expertise is a necessity, not an option.

PMID- 12053862
TI  - Clinical issues in the administration of an anti-epidermal growth factor receptor
      monoclonal antibody, IMC-C225.
AB  - OBJECTIVES: To review the clinical safety experience of the monoclonal antibody
      IMC-C225, focusing on two clinically important adverse events: acne-like rash and
      allergic reactions. In addition, practical administration issues are discussed.
      DATA SOURCES: Research articles. CONCLUSIONS: IMC-C225 administration is well
      tolerated and adverse events are mild and manageable. IMC-C225 can be safely and
      conveniently administered once weekly in outpatient settings. IMPLICATIONS FOR
      NURSING PRACTICE: Because nurses will be involved with administration of IMC-C225
      in the clinical setting, they must understand and be prepared to manage the acute
      and long-term adverse events associated with this agent.

PMID- 12053865
TI  - Adapting to industry changes provides clinical engineer with wealth of career
      opportunities.

PMID- 12053864
TI  - California BMET veteran adapts to the blurring of information technology and
      clinical engineering fields.

PMID- 12053866
TI  - University of Connecticut professor helps prepare the next generation of
      biomedical professionals.

PMID- 12053867
TI  - Are minidisc recorders adequate for the study of respiratory sounds?
AB  - Digital audio tape (DAT) recorders have become the de facto gold standard
      recording devices for lung sounds. Sound recorded on DAT is compact-disk (CD)
      quality with adequate sensitivity from below 20 Hz to above 20 KHz. However, DAT
      recorders have drawbacks. Although small, they are relatively heavy, the
      recording mechanism is complex and delicate, and finding one desired track out of
      many is inconvenient. A more recent development in portable recording devices is
      the minidisc (MD) recorder. These recorders are widely available, inexpensive,
      small and light, rugged, mechanically simple, and record digital data in tracks
      that may be named and accessed directly. Minidiscs hold as much recorded sound as
      a compact disk but in about 1/5 of the recordable area. The data compression is
      achieved by use of a technique known as adaptive transform acoustic coding for
      minidisc (ATRAC). This coding technique makes decisions about what components of
      the sound would not be heard by a human listener and discards the digital
      information that represents these sounds. Most of this compression takes place on
      sounds above 5.5 KHz. As the intended use of these recorders is the storage and
      reproduction of music, it is unknown whether ATRAC will discard or distort
      significant portions of typical lung sound signals. We determined the suitability
      of MD recorders for respiratory sound research by comparing a variety of normal
      and pathologic lung sounds that were digitized directly into a computer and also
      after recording by a DAT recorder and 2 different MD recorders (Sharp and Sony).
      We found that the frequency spectra and waveforms of respiratory sounds were not
      distorted in any important way by recording on the two MD recorders tested.

PMID- 12053869
TI  - A case study.... Lessons in contracting services.

PMID- 12053868
TI  - Engineering and governmental challenge: 7-day/24-hour chronobiologic blood
      pressure and heart rate screening: Part II.

PMID- 12053870
TI  - Wireless networking reshapes the face of patient monitoring systems.

PMID- 12053872
TI  - Unshielded Twisted Pair and Cat 5.

PMID- 12053871
TI  - The fundamentals of.... Medical laser technology.

PMID- 12053873
TI  - How certification exams are developed.

PMID- 12053874
TI  - [Normal values and evaluation of the German parents' version of Strengths and
      DIfficulties Questionnaire (SDQ): Results of a representative field study].
AB  - OBJECTIVE: The (SDQ) is a short questionnaire which addresses positive and
      negative behavioural attributes of children or adolescents. Being rated by
      parents or teachers, or as an equivalent self-report version, the 25 SDQ items
      were designed to include both strengths and difficulties. Although several
      reports have demonstrated the validity of the German SDQ, normative data have not
      yet been established. METHODS: In a nationwide representative field study, parent
      ratings were completed for 930 children and adolescents aged between 6 and 16
      years. Following verification of the scale structure by factor analysis, the
      observed distributions of scores were used to define normal, borderline, and
      abnormal score ranges. Possible effects of gender, age, and social class were
      also investigated. RESULTS: Factor analysis yielded an exact replication of the
      original scales. Several associations with gender, age, and social status
      attained statistical significance, but cut-off scores for the five subscales
      remained stable in different subgroups. Age- and sex-specific bandings for the
      total problem score reflected small differences between homogeneous subgroups.
      CONCLUSIONS: After replication and confirming the original scale factors, the
      availability of normative data further enhances the diagnostic value of the SDQ
      and facilitates future validation studies. Present evidence suggests that the SDQ
      may serve as a useful and economical screening measure, and in many other
      clinical and research settings.

PMID- 12053875
TI  - [Possible definitions and subsequent incidence of circumscribed reading and
      spelling disorders--theoretical considerations and empirical findings in a
      representative sample of young adults].
AB  - OBJECTIVES: With reference to an epidemiological sample of adolescents and young
      adults the impact of different models on the number of children classified as
      having specific reading and spelling problems is investigated. METHODS: Using the
      same set of data, the effects of alternative measurement models, definitions and
      methodological procedures on the prevalence of specific spelling problems are
      shown. The virtual consequences of various norm-oriented definitions of cases are
      discussed with reference to external empirical criteria. RESULTS: In the present
      study case definitions of specific spelling retardation based on substantial
      criteria result in prevalence rates between six and nine percent.

PMID- 12053876
TI  - [Theodor Ziehen as child and adolescent psychiatrist. A belated commemoration on
      the 50th anniversary of his death].
AB  - OBJECTIVE: The 50th anniversary of the death of Theodor Ziehen was on December
      29, 2000. As this occasion passed without fanfare, it is the authors' intent to
      recollect his importance in the field of child and adolescent psychiatry.
      METHODS: A short description of his life and an evaluation of his scientific work
      is presented based on earlier publications. RESULTS: Ziehen (1862-1950) was an
      extraordinarily versatile scholar. He is regarded as a great psychiatrist,
      psychologist and philosopher, as well as one of the founding fathers of child
      psychiatry. He began work on developmental psychiatry in Jena, publishing his
      first article "Association Psychology in Childhood" in 1898. He worked in close
      collaboration with the educators Rein and Truper. In 1902 the first part of his
      book "Mental Diseases in Childhood" was published, followed by further
      publications in 1904 and 1906. These volumes are regarded as the second most
      important in child psychiatry in Germany. His work is the first systematic and
      almost complete compendium in this field. Ziehen introduced the medical terms
      "affective psychosis" and "psychopathic constitution" to psychiatric literature.
      He also worked in the fields of medical education and education.

PMID- 12053877
TI  - [Symptom or illness? The exhausting life of an adolescent with chronic fatigue
      syndrome].
AB  - This case report presents the assessment of a 16-year old boy with chronic
      fatigue syndrome (CFS). Questions on the etiology, dynamics, diagnostics and
      treatment of this complex condition are briefly discussed.

PMID- 12053878
TI  - [Psychotic disorders and drug abuse in adolescents].
AB  - OBJECTIVES: The relation between substance abuse and symptoms of psychosis as
      well as related disorders was evaluated among patients at the Hospital for Child
      and Adolescent Psychiatry and Psychotherapy of the University of Marburg.
      METHODS: Using a child and adolescent version of the IRAOS (Instrument of the
      Retrospective Assessment of the Onset of Schizophrenia, Hafner et al., 1990), all
      patients with a co-morbid substance abuse were assessed. Patients with a drug
      induced psychosis (n = 8) were compared to psychotic patients with co-morbid
      substance abuse and to patients with other psychiatric disorders and substance
      abuse (n = 30). RESULTS: These three groups could be significantly distinguished
      on the basis of pre-morbid symptoms and pre-morbid functioning. CONCLUSIONS: The
      IRAOS shows some evidence that psychotic patients with co-morbid substance abuse
      can be distinguished from patients with a drug-induced psychosis according to the
      course of the initial psychopathology and pre-morbid functioning.

PMID- 12053880
TI  - [Quo vadis, pathology?].

PMID- 12053879
TI  - [Is there a temporal correlation between substance abuse and psychosis in
      adolescents?].
AB  - OBJECTIVES: The temporal relationship between substance abuse and symptoms of
      psychosis in adolescent patients was examined. METHODS: The hospital records of
      all adolescent inpatients admitted to the Central Institute of Mental Health in
      Mannheim during the period from 1976-1997 with a first-time diagnosis of
      psychosis were examined retrospectively for evidence of co-morbid substance
      abuse. RESULTS: In 18 of a total of 165 psychotic patients, co-morbid substance
      abuse was present, whose frequency rose after 1988, with a renewed increase since
      1996. Two of the 18 adolescents began taking drugs only after the appearance of
      the first symptoms of psychosis, in 13 others the abuse was already well
      established, while for the final three patients the onset of psychotic symptoms
      and substance abuse was congruent, occurring within the same month. A close
      temporal correlation between symptoms of psychosis and substance abuse was
      established for amphetamines (including ecstasy), LSD and excessive abuse of
      cannabis. CONCLUSIONS: Substance abuse constitutes a risk factor for the
      development of psychoses without, however, necessarily being a direct trigger of
      psychosis.

PMID- 12053881
TI  - [Relationship of the clinician and the pathologist at the turn of the
      millennium].
AB  - The autopsy, once a fundamental and familiar component of medical practice based
      on the good cooperation of clinicians and pathologist, is now infrequently used.
      Recent data indicate that autopsies are performed only about one third of the
      cases in Hungary and less that 1 of 10 inpatients death in the united States.
      Explanation for this decrease is multifactorial, involving changing professional
      and patients attitudes, the advent of sophisticated antemortem diagnostic
      methods, socioeconomic factors, and medicolegal concerns as well. Teaching
      institutions need to reevaluate concerning the need and practice of the autopsy.
      "The final audit" not always reflect well on clinical diagnoses and management of
      patients. Many facts proves that our modern tools still not enough to reach
      always a correct and safe diagnoses. Errors are still common in medicine. About
      10% of necropsies indicate a clinical managements different from what the
      patients received, 20% reveal additional diagnoses, and 60% of cases have
      teaching point. Though autopsy is expensive and time consuming, moreover the
      shortage of pathologist is evident, necropsy should remain the cornerstone of
      medicine in the new millennium as well. There are a broad range of different
      fields where pathologist and clinicians should work together in an everyday-
      setting--e.g. evaluate biopsy- or cytology-samples. Clinicopathological
      conferences are also important to discuss cases mainly for teaching purposes.
      Without maintaining the traditionally good cooperation neither clinicians nor
      pathologists will be able to give proper answers to the challenges and
      professional questions of the new era.

PMID- 12053882
TI  - [Postoperative vomiting].
AB  - INTRODUCTION: Nausea and vomiting following general anaesthesia are among the
      most frequent adverse reactions causing complications, the relief of which is an
      absolute demand. 5-HT3 receptor antagonists, such as ondansetron, belonging to
      the latest class of antiemetics were launched more than a decade ago.
      PATIENTS/METHODS: Efficacy and tolerability of ondansetron injection in
      prevention of postoperative nausea and vomiting were investigated in a
      prospective, randomised, double-blind, placebo controlled, three-armed clinical
      study in 148 patients undergoing laparoscopic cholecystectomy. Moreover the
      authors also investigated the effect of timing of dosing, i.e. whether the
      administration of antiemetic drug before starting anaesthesia has any advantage
      comparing its use at the end of operation. RESULTS: While using a standard
      surgical and anaesthesia method vomiting after laparoscopic cholecystectomy
      occurred in a frequency of 44.7% of the patients in the placebo group, whereas
      the figures decreased significantly after administration of 4 mg ondansetron at
      the end (28.9%) or before (25.5%) anaesthesia. Inclusively the frequency of
      severe cases decreased from 19.2% of control group up to 8.9% and 4.3% in the
      active groups, respectively. CONCLUSIONS: Intravenous administration of 4 mg
      ondansetron effectively reduces vomiting occurring in more than 40% of patients
      after laparoscopic cholecystectomy, especially the frequency of severe cases, and
      mainly if administered before operation. The preparation is safe; no clinical or
      laboratory adverse reactions, complications have been observed in the studied
      patients.

PMID- 12053883
TI  - [Early results of topotecan therapy in patients with recurrent ovarian cancer].
AB  - INTRODUCTION: Topotecan inhibits the topoisomerase-I enzyme resulting its
      stabilisation on the DNA and the suspension of replication and transcription.
      AIMS: The authors summarized their first experience on second-line topotecan
      treatment in a prospective non-randomized study. METHOD: Topotecan was given for
      recurrent epithelial ovarian cancer in the dose of 1.5 mg/m2/d for 5 days
      repeated in every 3 weeks in a 30-minute infusion intravenously. RESULTS: Twenty
      five recurrent ovarian cancer patients were treated between March, 1999 and
      March, 2001. Complete and partial response rates were found 12% and 12%,
      respectively. Stable disease was observed in 48% of patients for 4-8 courses,
      then progression continued. In these 3 groups of patients the median progression
      free interval was shown as 12 weeks. CONCLUSION: When comparing to previous
      chemotherapies, topotecan treatment failed to show a definitive improvement in
      the outcome of recurrent ovarian cancer.

PMID- 12053884
TI  - [Does the TT virus affect T-cell subgroups in patients undergoing hemodialysis?].
AB  - BACKGROUND: Recently many publications have appeared about the new DNA virus,
      called transfusion transmitted virus (TT virus), first described in 1997. These
      are mainly about the virus epidemiology, gene sequences and the distribution of
      different genotypes. In spite of the fact that the prevalence of this type of
      infection can reach 40 percent rate in polytransfused patients, such as in
      hemodialysis patients, the real pathogenetic effect of the virus has not yet been
      known. AIMS: The aim of the authors was to examine the activation and
      distribution of mononuclear cells in peripheral blood and to analyse the possible
      changes in Th1/Th2 immune regulatory mechanism through the soluble and
      intracellular cytokine profile beside the biochemical parameters of hepatic
      lesions in TT virus positive (n = 32) and negative (n = 17) hemodialysed
      patients. Healthy blood donors were the control group (n = 20). METHOD: Semi
      nested PCR was used to detect the DNA of TT virus. For the surface antigen (CD3,
      CD4, CD8, CD19, CD56, CD3/HLA-DR, CD3/CD69) and intracellular cytokine analysis
      the authors applied flow cytometric method. RESULTS: The authors did not find any
      differences in the liver specific biochemical parameters between TT virus
      positive and negative hemodialysed and the healthy control group. The number of
      total T, T helper and total B cells were decreased. The percentage of CD8+,
      CD3+/HLA-DR+, CD3+/CD69+ and CD56+ cells were increased significantly in both
      hemodialysed population independently the presence or absence of TT virus. The
      soluble and intracellular cytokines showed significant growth of the Th1/Th2
      cells ratio in hemodialysed patients, which has not been modified by the virus.
      CONCLUSIONS: From these results the authors assume that the TT virus does not
      cause any significant changes in the immune regulation, although it could play
      some role in the pathogenesis of hepatitis by local reaction.

PMID- 12053886
TI  - [Hungarian idioms and phrases connected with medical treatment].

PMID- 12053885
TI  - [Position statement of the College of Obstetrics and Gynecology regarding home
      childbirth, January 18, 2002].

PMID- 12053888
TI  - Neurolab: learning how the nervous system adapts to microgravity.

PMID- 12053887
TI  - Human water, sodium, and calcium regulation during space flight and exercise.
AB  - When one is exposed to microgravity, fluid which is normally pooled in the lower
      extremities is redistributed headward and weight bearing bones begin to
      demineralize due to reduced mechanical stresses. The kidney, which is the primary
      regulator of body fluid volume and composition, responds to the fluid shift and
      bone demineralization by increasing the urinary output of water, sodium, and
      calcium. This research involves developing a mathematical description of how
      water and electrolytes are internally redistributed and exchanged with the
      environment during space flight. This model consequently involves kidney function
      and the associated endocrine system. The model agrees well with actual data,
      including that a low sodium diet can prevent bone demineralization. Therefore,
      assumptions made to develop the model are most likely valid. Additionally,
      various levels of activity are also considered in the model since exercise may
      help to eliminate some of the undesired effects of space flight such as muscle
      atrophy and bone demineralization.

PMID- 12053889
TI  - [Secondary retention of permanent molars. I. Clinical, radiologic and histologic
      characterization].
AB  - The clinical, radiographical and histological aspects of secondary retention in
      permanent molars were studied in a group of 53 patients with 81 secondarily
      retained permanent molars. First molars turned out to be affected most
      frequently. The mean infraocclusion at the patients' first visit was 4.3 mm.
      After six months, infraocclusion had increased in adolescents. It seemed to be
      stable in adults. Tilting of adjacent teeth was observed in 39 cases of secondary
      retention. A solid, clear percussion sound and a partial absence of the
      periodontal ligament space on radiographs was only noted in less than 20% of the
      affected molars, while histological examination of 38 removed molars revealed
      that local areas of ankylosis were present in all cases. During a follow-up
      period of four years, six new cases of secondary retention were observed in the
      same population.

PMID- 12053890
TI  - [The clinical behavior of metal-composite post and core build-up. Results of a
      pilot study].
AB  - During the period 1974-1986 112 post and core buildups were inserted in 74
      patients. The buildups consisted of a metal prefabricated post (Dentatus,
      Unimetric or Radix) in combination with a composite core. After an average follow
      up period of 7.9 years 14 failures (12.5%) were noticed. Eight teeth could be
      rerestored and six teeth had to be extracted. However, when correction was made
      for teeth with a bad initial prognosis and for extractions not related to the
      buildup restoration, eight failures remained caused by failure of the buildup
      (7.5%). Half of these concerned Dentatus posts.

PMID- 12053891
TI  - [Oral health and ethnicity. An epidemiologic investigation in 5- and 11-year-olds
      in Amsterdam].
AB  - This study investigates whether the oral health of 5- and 11-year-old children of
      immigrants from Turkey and Morocco is worse than that of Dutch peer groups in
      Amsterdam. The outcome variables considered were dmft/s. DMFT/S and the index
      components, amount of plaque and number of tooth surfaces sealed (only 11-year
      olds). The explanatory variable considered was ethnicity (Turkish, Moroccan,
      Dutch, Surinam and 'Others'). The mean dmfs-score of Turkish and Moroccan 5-year
      olds was significantly higher than that of Dutch children: 8.1 and 8.2 vs. 3.6,
      respectively. Also a significant difference in mean DMFS-score between Turkish
      and Dutch 11-year olds was found; 3.3 vs. 1.7, but not between Moroccan and Dutch
      children. On average 1.8 surfaces were found sealed in 11-year olds. The mean
      plaque scores observed in Turkish and Moroccan five- and 11-year olds was
      significantly higher than in Dutch children. It was concluded that the oral
      health of Turkish and Moroccan children in Amsterdam was worse than that of their
      Dutch peer groups and that programs should be developed aimed at improving this
      situation.

PMID- 12053892
TI  - [Reaction to "The activity package of the dental assistant"].

PMID- 12053893
TI  - [Occupational differentiation, not for the dentist?].

PMID- 12053895
TI  - Family planning and reproductive health in China.

PMID- 12053896
TI  - ACOG committee opinion. Mode of term singleton breech delivery. Number 265,
      December 2001. American College of Obstetricians and Gynecologists.
AB  - Recently, researchers conducted a large, international multicenter randomized
      clinical trial comparing a policy of planned cesarean birth with planned vaginal
      birth. Given the results of this exceptionally large and well-controlled clinical
      trial, the American College of Obstetricians and Gynecologists Committee on
      Obstetric Practice recommends that obstetricians continue their efforts to reduce
      breech presentations in singleton gestations through the application of external
      cephalic version whenever possible. As a result of the findings of the study,
      planned vaginal delivery of a term singleton breech may no longer be appropriate.
      In those instances in which breech vaginal deliveries are pursued, great caution
      should be exercised. Patients with persistent breech presentation at term in a
      singleton gestation should undergo a planned cesarean delivery. A planned
      cesarean delivery does not apply to patients presenting in advanced labor with a
      fetus in the breech presentation in whom delivery is likely to be imminent or to
      patients whose second twin is in a nonvertex presentation.

PMID- 12053897
TI  - ACOG committee opinion. Placenta accreta. Number 266, January 2002. American
      College of Obstetricians and Gynecologists.
AB  - The incidence of placenta accreta has increased 10-fold in the past 50 years and
      now occurs with a frequency of 1 per 2,500 deliveries. Women who have had two or
      more cesarean deliveries with anterior or central placenta previa have nearly a
      40% risk of developing placenta accreta. If the diagnosis or strong suspicion of
      placenta accreta is formed before delivery, the patient should be counseled about
      the likelihood of hysterectomy and blood transfusion. Blood products and clotting
      factors should be available. Cell saver technology should be considered if
      available as well as the appropriate location and timing for delivery to allow
      access to adequate surgical personnel and equipment. A preoperative anesthesia
      assessment should be obtained.

PMID- 12053898
TI  - ACOG committee opinion. Exercise during pregnancy and the postpartum period.
      Number 267, January 2002. American College of Obstetricians and Gynecologists.
AB  - The physiologic and morphologic changes of pregnancy may interfere with the
      ability to engage safely in some forms of physical activity. A woman's overall
      health, including obstetric and medical risks, should be evaluated before
      prescribing an exercise program. Generally, participation in a wide range of
      recreational activities appears to be safe during pregnancy; however, each sport
      should be reviewed individually for its potential risk, and activities with a
      high risk of abdominal trauma should be avoided during pregnancy. Scuba diving
      also should be avoided throughout pregnancy because the fetus is at an increased
      risk for decompression sickness during this activity. In the absence of either
      medical or obstetric complications, 30 minutes or more of moderate exercise a day
      on most, if not all, days of the week is recommended for pregnant women.

PMID- 12053899
TI  - Three-quarter crown preparation.

PMID- 12053900
TI  - Surgical extraction of the mandibular canine tooth in the dog.

PMID- 12053901
TI  - [Influence of ursodeoxycholic acid on the therapeutic effects of low-calorie diet
      in obesity and hyperlipidemia rats with steatohepatitis].
AB  - OBJECTIVE: To explore the influence of ursodeoxycholic acid on the therapeutic
      effects of low-calorie diet in steatohepatitis with obesity and hyperlipidemia.
      METHODS: Thirty-five Sprague-Dawley rats fed with high-fat diet for 10 weeks were
      randomly allocated into 3 groups, and continued to experiment for 2 weeks. The
      animals in model group (n = 10) were still fed with high-fat diet; low-calorie
      diet group (n = 10) with common diet but only one third of the amount of normal
      demand; ursodeoxycholic acid group (n = 15) with low-calorie diet and
      ursodeoxycholic acid (15 mg/kg.d(-1)); and another 9 rats with common diet for 12
      weeks as normal group. RESULTS: Compared with normal group, such indexes as body
      weight, liver weight, and the level of serum lipids and aminotransferase were all
      increased significantly in model group. Furthermore, all rats in model group
      developed steatohepatitis. On the other hand, such indexes as body weight and the
      degree of steatosis in rats of low-calorie diet group were decreased sharply
      compared with those in model group, but neither disorders of serum lipid nor the
      degree of hepatic inflammation and necrosis in low-calorie diet group were
      improved obviously. Disorders of serum lipid, aspartate aminotransferase, hepatic
      inflammation and necrosis in ursodeoxycholic acid group were ameliorated to some
      extent. CONCLUSIONS: Ursodeoxycholic acid might help to improve the therapeutic
      effects of low-calorie diet on steatohepatitis with obesity and hyperlipidemia.

PMID- 12053902
TI  - Leadership and political influence.

PMID- 12053903
TI  - Generalized pustular reaction and ectopic flare of dermatitis caused by patch
      testing.

PMID- 12053904
TI  - Nonoccupational allergic contact dermatitis to cashew nut simulating
      photosensitivity eczema.

PMID- 12053906
TI  - [Life threatening Quincke edema. Can I really do without antihistaminics?].

PMID- 12053905
TI  - Allergy to propolis caused by beeswax-containing ointment.

PMID- 12053907
TI  - Breathe easy.

PMID- 12053908
TI  - [Care of psychiatric disorders: thoughts about human rights and the patient's
      rights].
AB  - Considering the social, political and economical changes such as occurred during
      the construction of the Psychiatric Nursing History, as well as the ongoing
      modifications in teaching nursing due the new Law for Directories and Bases, and
      taking also into account the existing preoccupation of some sections as far as
      the compliance with the Human Rights and Patient Rights are concerned, the
      present study proposes some reflections about the ethical conducts by nursing
      professionals in relation to patients interned in Psychiatric Hospitals, giving
      emphasis to the aspects related to the human dignity. The discussion is based in
      the Directory of the Rights of Patients proposed by the Secretary of Health of
      the Government of the State of Sao Paulo, as well as the Universal Declaration of
      Human Rights. The study gives furthermore emphasis to the responsibility in the
      area of teaching as far as the mobilization process for transforming the
      preconceptions regarding the mental diseases are concerned and examines the
      effective practice of equality, democracy, liberty and the exercise of the
      citizenship of the patient.

PMID- 12053911
TI  - A long-term perspective.

PMID- 12053909
TI  - [Influence of dose regimen on gentamycin nephrotoxicity in rats].
AB  - The acute renal failure (ARF), that still presents a right mortality rate (50%)
      can be defined as an abrupt decline of the glomerular filtration, resultant of
      ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent
      cause (27%) of ARF and it is suggested that the interval of administration of the
      drug can interfere in this side effect, however the best administration regimen
      is not very well established. This study evaluated the renal function of rats
      that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg),
      by intraperitoneal infusion. The results obtained in this research, indicated
      that the single infusion of gentamicin determined smaller nephrotoxicity by the
      reduction of serum concentration of this drug in 24 hours, decreasing the
      intracellular accumulation of this gentamicin, which is one of the main cellular
      mechanisms of this renal injury. The single dose treatment regime, otherwise,
      shows advantages not only related to the nephrotoxicity effect, but also it is
      relevant to the cost and safety, which can be rationable factors in the
      administration of this drug.

PMID- 12053912
TI  - Characterization of fowl adenovirus serotype-4 associated with hydropericardium
      syndrome in chicken.
AB  - The polypeptides of three fowl adenovirus-4 (FAV-4) field isolates of
      hydropericardium syndrome from various geographical areas of the country and the
      standard FAV-1 (CELO virus) were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and analysed by protein immunoblotting with
      polyclonal antibodies to FAV-4 and FAV-1. Protein profile analysis of FAV-4
      isolates revealed similarity of all the eight polypeptides with molecular weight
      ranging from 20 to 107 kDa but differed from CELO, particularly in their 24.2 kDa
      protein. Subsequent immunoblotting showed relatedness of at least five protein
      fractions of FAV-4 to CELO virus.

PMID- 12053913
TI  - Kinetics of interleukin-2 production in chickens infected with Eimeria tenella.
AB  - Interleukin (IL)-2 is a major cytokine of cell-mediated immunity (CMI). Because
      chickens infected with Eimeria, the causative agent of coccidiosis, develop a
      robust cell-mediated response against the parasite, we measured IL-2
      concentrations in vivo and in vitro during the course of primary and secondary
      experimental Eimeria tenella infections. IL-2 levels in serum and culture
      supernatants of spleen lymphocytes stimulated with mitogen or E. tenella
      sporozoites were significantly increased on day 7 post-primary infection compared
      with control group. This peak in IL-2 coincided with the time of maximum
      intestinal lesions as measured by cecum lesion scores. By contrast, during
      secondary infection highest IL-2 concentrations preceded intestinal lesions by 5
      days (day 2 versus day 7, respectively). These results confirmed that IL-2
      production is augmented during experimental coccidiosis and suggested that
      cellular immunity elicited during an anamnestic response to parasite reinfection
      is mediated, at least in part, by IL-2.

PMID- 12053914
TI  - Dynamics of a protective avian inflammatory response: the role of an IL-8-like
      cytokine in the recruitment of heterophils to the site of organ invasion by
      Salmonella enteritidis.
AB  - Increased resistance to Salmonella enteritidis (SE) organ infectivity in chickens
      can be conferred by the prophylactic administration of SE-immune lymphokines
      (ILK). Resistance is associated with an enhanced heterophilic accumulation within
      4 h of ILK injection. In these studies, the role of IL-8 in ILK-mediated
      heterophil recruitment during SE infections in young chickens was investigated.
      Heterophil accumulation was enhanced 2-4 h after the i.p. injection of both ILK
      and SE (ILK/SE) when compared to the control chicks. An i.p. injection of a
      rabbit polyclonal anti-human IL-8 antibody significantly (P < 0.01) reduced the
      accumulation of heterophils in the peritoneum after the injection of ILK/SE.
      Injections of preimmune rabbit IgG had no effect on peritoneal heterophil
      numbers. Within 2 h of injection of ILK/SE, a ten-fold increase in heterophil
      chemotactic activity was found in the peritoneal lavage fluid from these chicks
      compared to the saline control chicks. Pretreatment, with the anti-IL-8 antibody,
      of the peritoneal lavage fluids collected from the ILK/SE-treated chicks
      dramatically reduced this heterophil chemotactic activity. Treatment of the
      lavage fluids from all groups with preimmune IgG had no effect on heterophil
      chemotaxis. Additionally, pretreatment of ILK with the anti-human IL-8 antibody
      had no effect on heterophil chemotaxis. The results from these experiments
      suggest that IL-8 is produced locally by the host in response to both the SE
      infection and the ILK. With these studies, it was established that IL-8 is a
      major chemotactic factor produced by the host, which aids in mediating the ILK/SE
      induced recruitment of heterophils to the site of SE invasion.

PMID- 12053915
TI  - Antigenic heterogeneity amongst the field isolates of Newcastle Disease Virus
      (NDV) in relation to the vaccine strain. Part II: studies on viruses isolated
      from domestic birds in Israel.
AB  - Forty three Newcastle disease virus (NDV) strains isolated before and during 1997
      in Israel from domestic birds were studied by means of the three panels of
      monoclonal antibodies prepared against all the viral envelope proteins in order
      to reveal the possible antigenic differences between them and the VH strain used
      in Israel for poultry vaccination. Three isolates were found to have significant
      antigenic differences in the hemagglutinin-neuraminidase (HN) and fusion (F)
      glycoproteins as compared to the vaccine strain. As to the matrix protein, almost
      all the viruses isolated during the year 1997 were found to have considerable
      differences from the vaccine strain in two of four antigenic sites.

PMID- 12053916
TI  - Non-lethal infection parameters in mice separate sheep Type II Toxoplasma gondii
      isolates by virulence.
AB  - The zoonotic protozoan parasite Toxoplasma gondii can infect all warm-blooded
      animals, but virulence of isolates has previously been characterised mainly by
      the ability to kill mice after experimental infections. In the present study, 15
      Type II strains of T. gondii, isolated from five adult sheep, six sheep
      abortions, two pigs, one cat and one fox were examined for their virulence to
      young mice by less dramatic parameters. Clinical disease of inoculated mice,
      directly evidenced by reduced weight gain, was correlated to increase in serum
      level of haptoglobin and level of specific antibodies. Although Type II T. gondii
      strains are non-virulent to mice by lethality studies, significant differences in
      mouse virulence were observed between the strains of T. gondii isolated either
      from adult sheep or from sheep abortions. It was not possible to characterise
      strains isolated from sheep abortions as being more or less virulent than strains
      isolated from adult slaughter sheep.

PMID- 12053917
TI  - ["Veterinary genetics" and "Women in veterinary medicine", the main themes of the
      31rst WAHVM-congress in Brno (Czech Republic)].
AB  - The congress, held from 6-10 September 2000 on the campus of the University of
      Veterinary and Pharmaceutical Sciences in Brno, attracted 102 participants from
      23 countries, plus 20 accompanying persons. Next to a report on some special
      events as visits to the Veterinary Museum and the Mendelianum, after laying a
      wreath at Mendal's tomb, summaries or annotations are given of the lectures
      presented. There were five invited speakers in the session on "Veterinary
      genetics" and one invited speaker in the session devoted to "Women in veterinary
      medicine". Three guest speakers could be invited thanks to a grant by the
      "History of Medicine Programme" of The Wellcome Trust in London. The total number
      of lectures was 34. Besides some historical veterinary films were shown, and 34
      posters were on display. The congress was very well organized by a team presided
      by em.-professor Rudolf Bohm.

PMID- 12053918
TI  - [Feminization of veterinary medicine in the Netherlands 1925-2000].
AB  - The feminisation of veterinary medicine occurred in The Netherlands, as elsewhere
      in the world, in the course of the twentieth century. In 1930, Jeannette Voet
      (1907-1979) was the first female veterinarian graduate of the Faculty of
      Veterinary Medicine of Utrecht University. In contrast with the first Dutch
      female physician who graduated in 1878, Jeannette Voet was not an active
      feminist. Instead, she concentrated on the development of various fields of
      veterinary medicine during her career. Nevertheless, she played an important role
      in the acceptance of women in Dutch veterinary medicine. The integration of women
      into all areas of the veterinary profession was a gradual process. Meat
      inspection, in particular, proved to be rather conservative in its acceptance of
      female veterinarians. The number of women veterinarians in the profession
      increased only gradually throughout the twentieth century. In 1970, women
      represented not more than 5 % of all veterinarians in The Netherlands. A
      significant increase in female students was first observed in the 1980s. The
      large influx of city girls who are primarily interested in companion animal and
      horse medicine is still quite remarkable. The average percentage of female first
      year students between 1988 and 1992 was 60; over the last 5 years, this increased
      to 70%. Between 1988 and 1999, the average percentage of female graduates grew
      from 35 to 60%. Consequently, the proportion of Dutch female veterinarians
      increased from 5 to 25% between 1970 and 2000. In spite of this development, the
      representation of women veterinarians among policymaking officials, leading
      veterinary authorities and academic staff (particularly at the professor level)
      is still quite low. From this point of view, veterinary medicine could still be
      considered as 'a man's job'. Feminisation of veterinary medicine is often
      explained by an increase in the numbers of companion animals and horses and part
      time jobs or by a different, gender-based attitude towards animals. Another,
      simpler, explanation is that fewer male students are attracted to veterinary
      medicine because they can make more money in other professions. More historical
      sociological research, including a comparison with feminisation in other sciences
      and broader society, is necessary to obtain a deeper insight into this
      phenomenon. Regardless, feminisation is likely to further change the veterinary
      profession in the near future.

PMID- 12053919
TI  - Significant costs savings possible through improved ICU care, study finds.

PMID- 12053920
TI  - Advanced practice nurses lengthen survival of elderly cancer patients.

PMID- 12053921
TI  - Guidelines clarify drug therapy for congestive heart failure.

PMID- 12053922
TI  - Guidelines: drug therapy for HIV can start later.

PMID- 12053923
TI  - Storm over screening for prostate specific antigen. Innuendo in article is
      insulting.

PMID- 12053924
TI  - Storm over screening for prostate specific antigen. Give men facts on prostate
      cancer.

PMID- 12053925
TI  - Storm over screening for prostate specific antigen. Number needed to test needs
      to be known.

PMID- 12053926
TI  - Storm over screening for prostate specific antigen.  Summary of responses.

PMID- 12053927
TI  - Fusidic acid cream for impetigo. Judicious use is advisable.

PMID- 12053928
TI  - Fusidic acid cream for impetigo. Emergence of resistance to fusidic acid limits
      its use.

PMID- 12053929
TI  - Fusidic acid cream for impetigo. Problem may be clinically important.

PMID- 12053930
TI  - Fusidic acid cream for impetigo. Resistance trends must be monitored.

PMID- 12053931
TI  - Fusidic acid cream for impetigo. Findings cannot be extrapolated.

PMID- 12053932
TI  - The power of shame. Patients' perspective is also important.

PMID- 12053933
TI  - Declining altruism in medicine. Altruism is not equal to self sacrifice.

PMID- 12053934
TI  - Switzerland. Report aims to rescue science from doldrums.

PMID- 12053935
TI  - The rice genome and the minor grains.

PMID- 12053936
TI  - Altered peptide ligands and MS treatment.

PMID- 12053937
TI  - Reassessing research assessment in the UK.

PMID- 12053938
TI  - Major ongoing stroke trials.

PMID- 12053939
TI  - Effect of fluid and salt supplementation on body hydration of athletes during
      prolonged hypokinesia.
AB  - Body hydration decreases significantly during hypokinesia (HK) (diminished
      movement), but little is known about the effect of fluid and salt supplements
      (FSS) on body hydration during HK. The aim of this study was to measure the
      effect of FSS on body hydration during HK. Studies were done during 30 days pre
      HK period and 364 days HK period. Thirty male athletes aged 24.5 +/- 6.6 yr were
      chosen as subjects. They were equally divided into three groups: unsupplemented
      ambulatory control subjects (UACS), unsupplemented hypokinetic subjects (UHKS)
      and supplemented hypokinetic subjects (SHKS). Hypokinetic subjects were limited
      to an average walking distance of 0.7 km day-1. The SHKS group took daily 30 ml
      of water/kg body weight and 0.1 g of sodium chloride (NaCl)/kg body weight.
      Control subjects experienced no changes in their professional training and
      routine daily activities. Plasma volume (PV), urinary and plasma sodium (Na) and
      potassium (K), plasma osmolality, plasma protein, whole blood hemoglobin (Hb) and
      hematocrit (Hct), plasma renin activity (PRA) plasma aldosterone (PA) levels,
      physical characteristics, food and fluid intakes were measured. Plasma
      osmolality, plasma protein, urinary and plasma Na and K, whole blood Hct and Hb,
      PRA and PA levels decreased significantly (p < or = 0.01), while PV and body
      weight increased significantly (p < or = 0.01) in the SHKS group when compared
      with the UHKS group and did not change when compared with the UACS group. Plasma
      osmolality, plasma protein, urinary and plasma Na and K, PRA and PA, whole blood
      Hb and Hct levels increased significantly (p < or = 0.01), while PV body weight,
      food and fluid intakes decreased significantly (p < or = 0.01) in UHKS group when
      compared with the SHKS and UACS groups. The measured parameters did not change in
      the UACS group when compared with their baseline control values. It was shown
      that during HK body hydration decreased significantly, while during HK and FSS
      body hydration increased significantly. It was concluded that daily intake of FSS
      prevents the decrease of PV and blunts the increase of activity of the PRA and PA
      during prolonged HK.

PMID- 12053940
TI  - Tolerance of LSS plant component to elevated temperatures.
AB  - Stability of LSS based on biological regeneration of water, air and food subject
      to damaging factors is largely dependent on the behavior of the photosynthesizing
      component represented, mainly, by higher plants. The purpose of this study is to
      evaluate the tolerance of uneven-aged wheat and radish cenoses to temperature
      effects different in time and value. Estimation of thermal tolerance of plants
      demonstrated that exposure for 20 h to the temperature increasing to 45 degrees C
      brought about irreversible damage both in photosynthetic processes (up to 80% of
      initial value) and the processes of growth and development. Kinetics of visible
      photosynthesis during exposure to elevated temperatures can be used to evaluate
      critical exposure time within the range of which the damage of metabolic
      processes is reversible. With varying light intensity and air temperature it is
      possible to find a time period admissible for the plants to stay under adverse
      conditions without considerable damage of metabolic processes.

PMID- 12053941
TI  - Fluid and salt supplementation effect on body hydration and electrolyte
      homeostasis during bed rest and ambulation.
AB  - Bed rest (BR) induces significant urinary and blood electrolyte changes, but
      little is known about the effect of fluid and salt supplements (FSS) on
      catabolism, hydration and electrolytes. The aim was to measure the effect of FSS
      on catabolism, body hydration and electrolytes during BR. Studies were done
      during 7 days of a pre-bed rest period and during 30 days of a rigorous bed rest
      period. Thirty male athletes aged, 24.6 +/- 7.6 years were chosen as subjects.
      They were divided into three groups: unsupplemented ambulatory control subjects
      (UACS), unsupplemented bed rested subjects (UBRS) and supplemented bed rested
      subjects (SBRS). The UBRS and SBRS groups were kept under a rigorous bed rest
      regime for 30 days. The SBRS daily took 30 ml water per kg body weight and 0.1
      sodium chloride per kg bodyweight. Plasma sodium (Na), potassium (K), calcium
      (Ca) and magnesium (Mg) levels, urinary Na, K, Ca and Mg excretion, plasma
      osmolality, plasma protein level, whole blood hemoglobin (Hb) and hematocrit
      (Hct) level increased significantly (p < or = 0.05), while plasma volume (PV),
      body weight, body fat, peak oxygen uptake, food and fluid intake decreased
      significantly (p < or = 0.05) in the UBRS group when compared with the SBRS and
      UACS groups. In contrast, plasma and urinary electrolytes, osmolality, protein
      level, whole blood Hct and Hb level decreased significantly (p < or = 0.05),
      while PV, fluid intake, body weight and peak oxygen uptake increased
      significantly (p < or = 0.05) in the SBRS group when compared with the UBRS
      group. The measured parameters did not change significantly in the UACS group
      when compared with their baseline control values. The data indicate that FSS
      stabilizes electrolytes and body hydration during BR, while BR alone induces
      significant changes in electrolytes and body hydration. We conclude that FSS may
      be used to prevent catabolism and normalize body hydration status and electrolyte
      values during BR.

PMID- 12053942
TI  - Novel aquatic modules for bioregenerative life-support systems based  on the
      closed equilibrated biological aquatic system (C.E.B.A.S.).
AB  - The closed equilibrated biological aquatic system (C.E.B.A.S) is a man-made
      aquatic ecosystem which consists of four subcomponents: an aquatic animal
      habitat, an aquatic plant bioreactor, an ammonia oxidizing bacteria filter and a
      data acquisition/control unit. It is a precursor for different types of fish and
      aquatic plant production sites which are disposed for the integration into
      bioregenerative life-support systems. The results of two successful spaceflights
      of a miniaturized C.E.B.A.S version (the C.E.B.A.S. MINI MODULE) allow the
      optimization of aquatic food production systems which are already developed in
      the ground laboratory and open new aspects for their utilization as aquatic
      modules in space bioregenerative life support systems. The total disposition
      offers different stages of complexity of such aquatic modules starting with
      simple but efficient aquatic plant cultivators which can be implemented into
      water recycling systems and ending up in combined plant/fish aquaculture in
      connection with reproduction modules and hydroponics applications for higher land
      plants. In principle, aquaculture of fishes and/or other aquatic animals edible
      for humans offers optimal animal protein production under lowered gravity
      conditions without the tremendous waste management problems connected with
      tetrapod breeding and maintenance. The paper presents details of conducted
      experimental work and of future dispositions which demonstrate clearly that
      aquaculture is an additional possibility to combine efficient and simple food
      production in space with water recycling utilizing safe and performable
      biotechnologies. Moreover, it explains how these systems may contribute to more
      variable diets to fulfill the needs of multicultural crews.

PMID- 12053943
TI  - Report calls for drastic overhaul to improve quality in the U.S. health care
      system.

PMID- 12053944
TI  - ESRD management program cuts hospital utilization by 35 percent.

PMID- 12053945
TI  - COPD is under-reported and undertreated, survey finds.

PMID- 12053946
TI  - Better treatment of neonates' pain urged.

PMID- 12053947
TI  - Postmarket surveillance. Final rule.
AB  - The Food and Drug Administration (FDA) is implementing the postmarket
      surveillance (PS) provisions of the Federal Food, Drug, and Cosmetic Act (the
      act), as amended by the Food and Drug Administration Modernization Act of 1997
      (FDAMA). The purpose of this rule is to provide for the collection of useful data
      about devices that can reveal unforeseen adverse events or other information
      necessary to protect the public health.

PMID- 12053948
TI  - Trypanosoma cruzi: effect of parasite subpopulation on murine pregnancy outcome.
AB  - C3H/HeN female mice infected with distinct Trypanosoma cruzi subpopulations (RA
      strain [pantropic/reticulotropic] and K98 clone of the CA-I strain [myotropic])
      show differences both in inflammatory compromise of the genital tract and in the
      outcome of pregnancy. The group of mice infected with the K98 clone show
      lymphomononuclear infiltrates in pelvian fat and in uterus interstitium,
      coexisting with the presence of T. cruzi DNA, and show moderate oophoritis,
      perioophoritis, and vasculitis. However, neither parasite DNA nor inflammatory
      foci were detected in the uterus, and only mild oophoritis was observed among RA
      infected mice at mating time. Independently from the parasite subpopulation,
      females developed estrous 30 days postinoculation (PI), and at the same time,
      parasite counts were similar for K98 and for RA-infected mice. However, fertility
      was significantly diminished in K98-infected females. On day 14 of gestation,
      fetal resorptions increased in this group and cannot be attributed to hormonal
      disbalance because similar serum progesterone levels were found in all groups. At
      this time (44 days PI), parasitemia was higher in K98- than in RA-infected mice.
      However, resorptions were not triggered by massive infection because polymerase
      chain reaction failed to prove parasite DNA in resorbing fetuses. In contrast
      with K98 females, RA-infected mice delivered T. cruzi-infected newborns.

PMID- 12053949
TI  - Wallinia chavarriae n. sp. (Trematoda: Macroderoididae) in Astyanax aeneus
      (Gunther, 1860) and Bryconamericus scleroparius (Regan, 1908) (Osteichthyes:
      Characidae) from the Area de Conservacion Guanacaste, Costa Rica.
AB  - Wallinia chavarriae n. sp. is described from the small-bodied characids Astyanax
      aeneus and Bryconamericus scleroparius in the Area de Conservacion Guanacaste,
      northwestern Costa Rica. The species differs from W. valenciae in possessing an
      acetabulum that is smaller than the oral sucker and vitelline follicles that are
      ovoid or rounded rather than elongate and tubular. Detailed comparison between
      these 2 species is handicapped by the less than satisfactory condition of the
      type and only museum specimen of W. valenciae. Wallinia chavarriae and W.
      valenciae belong to a subfamily of trematodes, Walliniinae, that arguably
      includes Creptotrematina spp., Magnivitellum simplex, and possibly Margotrema.
      The morphology of walliniines suggests that they are macroderoidids, but a
      clearer understanding of their classification could be gained from their larval
      morphology or from molecular systematic studies. The host associations of a
      monophyletic Walliniinae would indicate diversification within 2 groups of
      freshwater fishes: the neotropical characids for species of Wallinia,
      Creptotrematina, and Magnivitellum and the endemic central Mexican goodeids for
      those of Margotrema. The biogeography and host associations of these parasites
      provide a system for studies of potential host switching and vicariance,
      involving the middle-American and neotropical regions.

PMID- 12053950
TI  - Sarcocystis mephitisi n. sp. (Protozoa: Sarcocystidae), Sarcocystis neurona-like
      and Toxoplasma-like infections in striped skunks (Mephitis mephitis).
AB  - Two structurally distinct types (A, B) of microscopic sarcocysts were found in
      muscles of 4 of 5 feral skunks. Type A sarcocysts had sarcocyst walls of up to 6
      microm thick. The villar protrusions (Vp) on the sarcocyst wall were up to 5
      microm long. The Vp were constricted at the base, expanded in the middle, and had
      a blunt tip. Numerous microtubules were present in the Vp and in the granular
      layer. Bradyzoites were up to 11 microm long and up to 3.2 microm wide. Based on
      the distinctiveness of the Vp, a new name, Sarcocystis mephitisi is proposed for
      type A sarcocysts. Type B sarcocysts had a relatively thin (approximately 1-2
      microm thick) sarcocyst wall and the Vp were slender and tapered toward the tip.
      These sarcocysts were structurally similar to S. neurona sarcocysts. A Toxoplasma
      gondii-like tissue cyst was found in a section of tongue of 1 of the 4 skunks.

PMID- 12053951
TI  - Dicyemennea canadensis n. sp. (phylum Dicyemida) from Bathypolypus arcticus
      (Mollusca: Cephalopoda: Octopoda).
AB  - Dicyemennea canadensis n. sp. is described from a bathyal octopus collected off
      Canada in the Bay of Fundy. The dicyemid is a small species that rarely exceeds
      600 microm in length. The vermiform stages are further characterized as having 17
      23 peripheral cells, a conical-shaped calotte, an axial cell that extends to the
      base of the propoplar cells, and no abortive axial cells. Infusoriform embryos
      consist of 37 cells. There is 1 nucleus in each urn cell, and refringent bodies
      are absent. This is the first dicyemid to be described from the cephalopod
      Bathypolypus arcticus (Prosch. 1847), and the first dicyemid reported from
      Canada. In addition, it is the first species of Dicyemennea from the northwestern
      Atlantic Ocean to be described.

PMID- 12053952
TI  - Life cycle of Brachylaima mascomai n. sp. (Trematoda: Brachylaimidae), a parasite
      of rats in the Llobregat delta (Spain).
AB  - The terrestrial triheteroxenous life cycle of Brachylaima mascomai n. sp.
      (Trematoda: Brachylaimidae) is elucidated. Operculated, assymetric, embryonated
      eggs (25.4 x 12.7 microm) are passed with feces of the natural (Rattus norvegicus
      and R. rattus) and experimental (albino and wild mice, albino rats, Apodemus
      sylvaticus, Mus spretus [Muridae] and the golden gerbil) definitive hosts and
      ingested by the helicid gastropod Pseudotachea splendida, the only natural and
      experimental first intermediate host. Microcaudate cercariae harbored in branched
      sporocysts in the digestive gland emerge from this snail and contact P.
      splendida, Otala punctata, Theba pisana, and Helix (C.) aspersa snails developing
      into unencysted infective metacercariae in the kidney. Definitive hosts are
      infected by ingestion of infected snails; the adult parasites inhabit the small
      intestine. Chaetotaxic cercarial pattern specific at acetabular (S(II) 8-10
      papillae) and cephalic (C(III) 13-15 papillae, H 16 papillae) levels. Three types
      of cercarial papillae are observed by scanning electron microscopy (SEM) and
      their arrangement is correlated with chaetotaxy for the first time in trematodes:
      argentophilic papillae with fingerlike process (cephalic, body, and acetabular
      levels), argentophilic papillae with opening (2 papillae in the M body level),
      and nonargentophilic dome-shaped papillae (alternated with argentophilic S(II)
      papillae on the ventral sucker). SEM detected interlacing network of ridges
      covering the metacercarial body. Adults with multidigitate tegumentary spines
      were observed by SEM. Subequal suckers; the acetabulum located in the posterior
      part of anterior fifth of body. Vitellaria extend from between middle level and
      anterior margin of anterior testis to between middle level and posterior margin
      of acetabulum. Uterus almost reaches the intestinal bifurcation.

PMID- 12053953
TI  - New molecular evidence that Teladorsagia circumcincta (Nematoda:
      Trichostrongylidea) is a species complex.
AB  - In the polymorphic Teladorsagia circumcincta (morphs circumcincta and
      trifurcata), a sheep and goat line (SGL) and a goat line (GL) have been
      previously described on the basis of the malate dehydrogenase allozyme
      polymorphism (MDH-2) and of the morphology of the dorsal ray. The GL were never
      found alone in 1 host, so the status of species was not given to these 2 lines.
      To investigate further whether there are other genetic markers that will
      delineate them, we collected T. circumcincta worms from goat and sheep at 8 farms
      in Touraine (west-central France). The worms were identified individually as
      being SGL or GL on the basis of MDH-2 polymorphism. This distinctiveness was
      corroborated by sequences of the beta-tubulin isotype I gene, the second internal
      transcribed spacer (ITS2) of their rDNA, and the nicotinamide dehydrogenase (ND4)
      gene of their mDNA. The extent of the divergence in the 3 additional genetic
      markers was such that SGL and GL may be considered as 2 species. A third putative
      species was found in the SGL line based exclusively on the ND4 gene. These
      findings suggest that T. circumcincta is a species complex and that further
      investigation is required on a wider geographic scale.

PMID- 12053954
TI  - Schistosoma mansoni sporocysts in culture: host plasma hemoglobin contributes to
      in vitro oxidative stress.
AB  - The initiation and promotion of sporocyst propagation and subsequent production
      of cercariae by intramolluscan larval stages of digenic trematodes are thought to
      depend on mollusc-derived factors. The ability to investigate this using in vitro
      cultures of Schistosoma mansoni sporocysts has been impeded by the fact that
      plasma from the host, Biomphalaria glabrata, becomes toxic to the parasite in
      long-term cultures. The present study identifies hemoglobin as the plasma
      component responsible for this toxicity. The addition of the enzyme catalase to
      sporocyst cultures neutralized the toxic effects of both purified hemoglobin and
      whole plasma, suggesting that the generation of H2O2 as a consequence of
      hemoglobin oxidation is the mechanism of plasma toxicity. Furthermore, cultures
      incubated in unconditioned schistosome medium with plasma plus catalase yielded
      significantly higher numbers of daughter sporocysts than cultures with media or
      plasma alone, but not higher than cultures with catalase alone. These latter
      results suggest that the oxidative environment and the antioxidant capacity of
      the media are critical factors for in vitro propagation of S. mansoni sporocysts.

PMID- 12053955
TI  - Spiracanthus bovichthys n. gen. n. sp. (Acanthocephala: Arhythmacanthidae), a
      parasite of littoral fishes of the central south coast of Chile.
AB  - A new acanthocephalan species, Spiracanthus bovichthys n. gen. n. sp., is
      described. Samples were taken from 26 marine fish species between 23 and 53
      degrees S of Chile. The parasite was found in the intestine of 6 species and only
      between 36 and 40 degrees S, especially in those fish that prey on small
      crustaceans in the upper and sublittoral zone. The parasite was found in
      Bovichthys chilensis (Reagan). Auchenionchus variolosus (Valenciennes),
      Calliclinus genigutattus (Valenciennes), Sindoscopus australis (Fowler and Bean),
      Myxodes cristatus Valenciennes, and Gobiesox marmoratus (Jenyns). However, only
      the first species is a suitable host for the parasite as evidenced by the
      presence of mature females. This acanthocephalan belongs to Arhythmacanthidae,
      but it does not correspond to any genus described. Spiracanthus bovichthys is
      different in the number and spiralled distribution of its hooks in the proboscis.
      In the short proboscis, 3 groups of hooks are distinguished according to size,
      summing up to 150-190 hooks. The group of largest hooks are found in the apical
      part of the proboscis, and there are 10 diagonal rows of small hooks from the
      prebasal to basal proboscis. Its trunk is covered partially by small spines.
      Amphipod and isopods were the prey items shared among the host fish species and
      are the best candidates to be the intermediate hosts of S. bovichthys.

PMID- 12053956
TI  - PCR diagnostics underestimate the prevalence of avian malaria (Plasmodium
      relictum) in experimentally-infected passerines.
AB  - Several polymerase chain reaction (PCR)-based methods have recently been
      developed for diagnosing malarial infections in both birds and reptiles, but a
      critical evaluation of their sensitivity in experimentally-infected hosts has not
      been done. This study compares the sensitivity of several PCR-based methods for
      diagnosing avian malaria (Plasmodium relictum) in captive Hawaiian honeycreepers
      using microscopy and a recently developed immunoblotting technique. Sequential
      blood samples were collected over periods of up to 4.4 yr after experimental
      infection and rechallenge to determine both the duration and detectability of
      chronic infections. Two new nested PCR approaches for detecting circulating
      parasites based on P. relictum 18S rRNA genes and the thrombospondin-related
      anonymous protein (TRAP) gene are described. The blood smear and the PCR tests
      were less sensitive than serological methods for detecting chronic malarial
      infections. Individually, none of the diagnostic methods was 100% accurate in
      detecting subpatent infections, although serological methods were significantly
      more sensitive (97%) than either nested PCR (61-84%) or microscopy (27%).
      Circulating parasites in chronically infected birds either disappear completely
      from circulation or to drop to intensities below detectability by nested PCR.
      Thus, the use of PCR as a sole means of detection of circulating parasites may
      significantly underestimate true prevalence.

PMID- 12053957
TI  - Effect of ozone treatment on Eimeria colchici oocysts.
AB  - The effect of ozone on the inhibition of the sporulation of Eimeria colchici
      oocysts in vitro was examined. Lower sporulation ratios were found to correspond
      directly to longer ozone exposure time. In pheasants, Phasianus colchicus, orally
      inoculated with ozone-treated oocysts, lower mortality and lower oocysts per gram
      of feces were observed as compared with birds given untreated oocysts. Thus,
      treatment of E. colchici oocysts with ozone alone was observed to partially
      inhibit the growth and infectivity of the oocysts.

PMID- 12053958
TI  - Antischistosomal bioactivity of isoflavonoids from Millettia thonningii
      (Leguminosae).
AB  - Extracts of the seeds of the leguminous tree Millettia thonningii are
      molluscicidal and schistosomicidal and contain a mixture of isoflavonoids and 3
      phenylcoumarins. Robustic acid and a pure mixture of alpinumisoflavone and
      dimethylalpinumisoflavone, as characterized by nuclear magnetic resonance, were
      isolated from a dichloromethane extract. The bioactivity of these compounds
      against Schistosoma mansoni miracidia, cercariae, and adult worms was tested in
      vitro. Both robustic acid and the alpinumisoflavone mixture killed cercariae and
      adult schistosomes in vitro. At sublethal concentrations of the isoflavonoids,
      reductions in miracidial motility were measured using a video-imaging technique.
      The inhibition of mitochondrial electron transport at site I by the isolated
      isoflavonoids was also investigated. The results suggest that robustic acid and
      at least 1 alpinumisoflavone compound from the dichloromethane extract of the
      seeds of M. thonniogii are responsible for some of the observed bioactivity of
      this extract against schistosomes.

PMID- 12053959
TI  - Effect of management interventions on the helminth parasites recovered from
      donkeys in South Africa.
AB  - The helminth burdens and biodiversity of 9 randomly selected donkeys (Equus
      asinus) were examined after necropsy. Prior to necropsy, 8 of the animals were
      subjected to 1 of 3 management interventions (monthly fecal removal, prewinter
      moxidectin treatment, and a combination of both treatments) or a control for a 16
      mo period. The remaining animal was killed earlier in the study. Quantitative
      samples were collected from the gastrointestinal tract for helminth recovery. The
      intestinal walls were examined with transmural illumination and thereafter
      digested with a HCl-peptic method for identification of the mucosal larval stages
      of cyathostomes. In this study, 37 helminth species belonging to the Ascarididae,
      Atractidae, Dictyocaulidae. Habronematidae, Onchocercidae, Oxyuridae,
      Strongylidae, and Trichostrongylidae, 1 cestode species of the Anoplocephalidae,
      and 1 trematode species in the Paramphistomatidae were recovered. In addition, 1
      species of oestrid fly of the Gasterophilidae was identified. The results
      obtained in the present study support the application of several intervention
      methods to reduce the helminth burdens in donkeys.

PMID- 12053960
TI  - Alternative migration routes of Ascaris suum in the pig.
AB  - Experiments were conducted to investigate possible alternative routes of
      extraintestinal migration of Ascaris suum larvae in the pig. Pigs were infected
      with A. suum via injection of newly hatched larvae into cecal veins (i.v.), into
      cecal lymph nodes (LN), or intraperitoneally (i.p.), and control animals were
      inoculated orally with infective eggs (p.o.). Two pigs per inoculation route were
      necropsied on days 1, 4, and 13 postinoculation. The numbers of liver lesions and
      the percentage of larvae recovered was considerably greater in pigs inoculated
      i.v. or p.o. on each necropsy day. However, irrespective of inoculation route, at
      least a proportion of larvae passed through the livers and were able to complete
      migration to the small intestine by day 13. The results indicate that larval
      penetration of the intestinal wall is not necessary for liver-lung migration and
      that passage through the liver may be favorable for migrating A. suum larvae,
      although a delayed arrival in the small intestine cannot be ruled out for larvae
      following alternative routes.

PMID- 12053961
TI  - Behavior favoring transmission in the viviparous monogenean Gyrodactylus
      turnbulli.
AB  - Transmission by Gyrodactylus turnbulli occurs most frequently when its hosts
      (Poecilia reticulata) come into close contact. This study is the first
      description of a specific migratory behavior that facilitates transmission of a
      gyrodactylid from dead hosts. Recently-dead guppies typically float at the
      water's surface; G. turnbulli moves off these fish into the water film, hanging
      motionless with the haptor held by surface tension. Because guppies are surface
      feeders, detached parasites in the water film are more likely to contact a new
      host.

PMID- 12053962
TI  - Efficacy of beta-cyclodextrin against experimental cryptosporidiosis in neonatal
      lambs.
AB  - The efficacy of beta-cyclodextrin against experimental Cryptosporidium parvum
      infection was evaluated in neonatal lambs. The animals were treated by oral
      administration of the drug at 1 g/kg of body weight during 3 consecutive days.
      Preventive treatment was started within 1 day of birth, and therapeutic treatment
      was initiated at the onset of diarrhea following confirmation of infection.
      Disease development and drug efficacy were evaluated by monitoring the presence
      or absence of diarrhea and oocyst shedding from birth until 30 days of age.
      Weight gains at 15 and 30 days of age were also recorded. Beta-cyclodextrin was
      highly effective as a prophylactic treatment; 1 animal did not acquire the
      infection, diarrhea was prevented in infected animals, and there was a
      considerable decrease in oocyst shedding. The therapeutic treatment was effective
      in decreasing the severity of diarrhea and the duration of oocyst shedding. The
      animals tolerated the drug well, and there was a significant increase in their
      body weights.

PMID- 12053964
TI  - Baylisascaris procyonis (Nematoda: Ascaridoidea) eggs in raccoon (Procyon lotol)
      latrine scats in Orange County, California.
AB  - Baylisascaris procyonis is the common intestinal nematode of the raccoon and is
      well-recognized as a cause of visceral, ocular, and neural larva migrans in many
      species of wild and domestic birds and mammals, including humans. To develop data
      on the prevalence of B. procyonis in Orange County, California, 800 distinct
      raccoon latrine sites were sampled in 4 spatial zones from 15 January to 31
      December 2000. Counts of fecal eggs per gram (EPG) were determined and evaluated
      with reference to spatial zone and season of collection. No significant
      differences in EPG were noted among the spatial zones. However, EPG exhibited a
      significant rise (37,730 +/- 1,865) in the fall and a significant decline (26,204
      +/- 1,446) in the winter (ANOVA, P = 0.045). The overall egg prevalence was 100%,
      and the overall mean EPG was 30,265 +/- 867.

PMID- 12053963
TI  - Parasites of swordfish from the Gulf of Guinea.
AB  - Ten parasite species were identified after a study carried out on 125 swordfish
      from the Gulf of Guinea waters. The samples were taken between August and
      November 1997; 3 of the parasite species, Caligus coryphaenae. Pelichnibothrium
      speciossum, and Sphyriocephalus viridis were recorded for the first time on this
      host.

PMID- 12053965
TI  - First descriptions of early- and middle-stage copepodids of Anthosoma crassum
      (Dichelesthiidae: Siphonostomatoida) and lesions on shortfin makos (Isurus
      oxyrinchus) infected with A. crassum.
AB  - Early- and middle-stage copepodids of Anthosoma crassum (Dichelesthiidae:
      Siphonostomatoida) and lesions associated with A. crassum infections are
      described from samples collected from the jaws of shortfin makos captured off
      southern California. The copepodids did not possess frontal filaments or frontal
      organs, and they resided in a headstandlike position firmly attached by their
      embedded antennae. Copepod larvae and small adults were lodged in shallow mucosal
      ulcers that basally exhibited mild, acute granulocytic stomatitis; large adults
      were lodged in deep tunnels encompassing the anterior aspects of their bodies.
      Some lesions contained more than I copepod. Examinations of lesions revealed that
      A. crassum infection of shortfin makos can result in severe subacute, necrotizing
      stomatitis with hemorrhage, granulation tissue, and lymphocytic aggregations in
      the mucosa, and reactive lymphocytic infiltration of the submucosal skeletal
      muscle. Copepod gut contents consisted of shark erythrocytes, hemosiderin
      granules, and necrotic host cells. These observations, along with reports of
      sharks heavily infected with A. crassum, suggest that this copepod may sometimes
      play a role in the morbidity and mortality of sharks that it infects.

PMID- 12053966
TI  - Observations on mouthparts of Dermatobia hominis (Linneaus Jr., 1781) (Diptera:
      Cuterebridae) by scanning electron microscopy.
AB  - The ultrastructure of the mouthparts of Dermatobia hominis was studied using
      scanning electron microscopy. The morphological characteristics of the segments,
      articulations, sensory organs, and pilose covering are described.
      Mechanoreceptors of the long trichoid sensillum and smaller trichoid sensillum
      types were observed, as well as labellar gustatory receptors of the basiconic
      sensillum type, which differed between the sexes. These observations are
      discussed with reference to the current literature on the morphology and sense
      organs of dipteran mouthparts, and the prevailing view that the adult mouthparts
      of this species are non-functional is challenged.

PMID- 12053967
TI  - Prevalence and intensity of Haemobaphes diceraus (Copepoda: Pennellidae) from
      shiner perch, Cymatogaster aggregata (Embiotocidae).
AB  - The prevalence and intensity of the hematophagous pennellid copepod Haemobaphes
      diceraus were monitored over a 10-mo period in shiner perch Cymatogaster
      aggregata at Pipers Lagoon, Nanaimo, British Columbia. The prevalence and mean
      intensity of metamorphosed adult female H. diceraus (n = 421) were 10.0% and 1.2
      (+/-0.5 SD), respectively. The majority (97.9%) of infected fish had single
      infections, reflecting the possibility of intensity-dependent parasite-induced
      mortality, rejection of additional parasites, or both. Transforming females were
      detected throughout the year; however, there was no detectable seasonal pattern
      of colonization. Neither copepodids nor adult males of H. diceraus were observed
      on the gills of shiner perch, and this was consistent with the hypothesis that an
      intermediate host harbors these stages. Males of Haemobaphes sp. infected the
      gills of bay pipefish Syngnathus griseolineatus with a prevalence and mean
      intensity of 56.0% and 6.8 +/- 3.7, respectively. Transmission of H. diceraus to
      shiner perch probably occurs in inshore protected areas, where shiner perch
      ecologically overlap with the probable intermediate host of H. diceraus, the bay
      pipefish.

PMID- 12053968
TI  - Congenital toxoplasmosis in a Indo-Pacific bottlenose dolphin (Tursiops aduncus).
AB  - Toxoplasma gondii was identified in tissues of a stillborn late-term fetus from
      an Indo-Pacific bottlenose dolphin (Tursiops aduncus). Myocardial necrosis and
      nonsuppurative inflammation in the heart and nonsuppurative necrotizing
      encephalitis were associated with tachyzoites and tissue cysts. The diagnosis was
      confirmed by immunohistochemical staining with anti-T. gondii-specific polyclonal
      rabbit serum.

PMID- 12053969
TI  - Cloning and molecular characterization of the cDNA encoding histone H1 from
      Leishmania braziliensis.
AB  - The isolation and molecular characterization of the histone H1-encoding gene from
      Leishmania braziliensis was carried out. The gene is present in the genome as a
      single copy and transcribed as a polyadenylated transcript of 830 nucleotides.
      The deduced amino acid sequence has in its central region the DNA binding K-[K/R]
      A-A-[A/P] motif, which is repeated in tandem 9 times.

PMID- 12053970
TI  - Occurrence of Bunodera sacculata Van Cleave and Mueller, 1932 in Perca flavescens
      from Silver Creek and Silver Lake, Michigan.
AB  - Bunodera sacculata (Trematoda: Allocreadiidae) infected 65 (54%) of 120 yellow
      perch collected in 1997 and 40 (50%) of 80 perch from Silver Creek in 1998. and
      17 (30%) of 56 perch in 2000 from Silver Lake in lower Michigan. Gravid B.
      sacculata occurred in the pyloric ceca and anterior intestine. There were
      differences in monthly trends (July through August) in prevalences, mean
      intensities, and mean abundances of B. sacculata in Silver Creek between 1997 and
      1998. The mean intensity +/- SD (8.2 +/- 9.1) and mean abundance (4.1 +/- 7.8) of
      B. sacculata were significantly higher in 1998 than in 1997 and 2000. An
      additional 20 perch (0+ in age) collected from the creek in July 1998 were all
      infected and had the highest mean intensity of 21.3 +/- 14.1.

PMID- 12053971
TI  - Hepatic sarcocystosis in a striped dolphin (Stenella coeruleoalba) from the
      Spanish Mediterranean coast.
AB  - Fatal hepatic sarcocystosis was diagnosed in a striped dolphin (Stenella
      coeruleoalba) from the northeastern Spanish Mediterranean coast based on
      pathologic findings and the microscopic and ultrastructural characteristics of
      the intralesional parasite. Main gross lesions were icterus, subcutaneous
      hemorrhages, and hepatic congestion. The most prominent microscopic lesions
      consisted of severe acute multifocal to coalescing necrotizing hepatitis with
      cholestasis and intralesional protozoa. There was severe chronic pancreatitis
      with generalized distension of pancreatic ducts by hyaline plugs and adult
      trematodes. Only asexual stages of the protozoa were found. The parasite in the
      liver divided by endopolygeny. Schizonts varied in shape and size. Mature
      schizonts had merozoites randomly arranged or budding peripherally around a
      central residual body. Schizonts were up to 22 microm long, and merozoites were
      up to 6 microm long. Ultrastructurally, merozoites lacked rhoptries. This
      parasite failed to react by immunohistochemistry with anti-Toxoplasma gondii,
      anti-Neospora caninum and anti-Sarcocystis neurona antibodies. The microscopic
      and ultrastructural morphologies of the parasite were consistent with Sarcocystis
      canis, so far described only from animals in the Unites States. The life cycle
      and source of S. canis are unknown. The present report of S. canis-like infection
      in a sea mammal from Spain indicates that the definitive host for this parasite
      also exists outside of the United States.

PMID- 12053973
TI  - Ocular angiostrongyliasis without meningitis symptoms in Okinawa, Japan.
AB  - A 62-year-old female farmer presented with retinal detachment in her left eye,
      and an Angiostrongylus cantonensis worm was recovered by vitreous surgery. The
      case did not show typical clinical symptoms indicating meningitis, although the
      patient complained of a mild headache, a low-grade fever, and slight ataxia. The
      symptoms were treated as influenza before the onset of the retinal detachment.
      The present case is the first confirmed of ocular angiostrongyliasis in Japan.

PMID- 12053972
TI  - Anticryptosporidial prophylactic efficacy of enrofloxacin and paromomycin in
      chickens.
AB  - Two battery tests were conducted to study the anticryptosporidial prophylactic
      efficacy of the 2 commercially available antibiotics, enrofloxacin and
      paromomycin. The efficacy of enrofloxacin was 52% at the recommended level, which
      could not be increased, using twice the recommended dose. At the recommended
      levels, paromomycin reduced the oocyst output of birds by 67-82%, showing the
      highest efficacy of all drugs tested against avian cryptosporidiosis thus far.
      Moreover, the patent period was shortened by 12-23%. The body weight gain of
      paromomycin-treated chickens was almost identical with that of uninfected,
      untreated control birds irrespective of dosage, indicating the lack of toxicity.
      Although paromomycin is not registered for use in birds, in combination with
      sanitary procedures and disinfection, it may help in the control of
      cryptosporidiosis in some bird facilities.

PMID- 12053974
TI  - Molecular characterization of Cryptosporidium sp. isolated from northern Alaskan
      caribou (Rangifer tarandus).
AB  - Cryptosporidium sp. was found in 3 out of 49 caribou (Rangifer tarandus) from
      northern Alaska. Segments of both the 18S ribosomal RNA and the heat shock
      protein genes were amplified from the caribou isolate and compared with that
      obtained from an isolate from a wild white-tailed deer (Odocoileus virginianus)
      in Virginia as well as other species and isolates available from GenBank.
      Analyses showed the white-tailed deer isolate to be identical with the C. parvum
      cattle genotype; however, the caribou isolate represents a new genotype closely
      related to C. serpentis, C. muris, and C. andersoni. Giardia sp. was not detected
      in any of the caribou samples nor was Cryptosporidium sp. or Giardia sp. detected
      in any of the 42 moose (Alces alces) samples examined.

PMID- 12053975
TI  - Taeniacanthodes dojirii n. sp. (Copepoda: Poecilostomatoida: Taeniacanthidae),
      from Cortez electric rays (Narcine entemedor: Torpediniformes: Narcinidae)
      captured in the Gulf of California, and a phylogenetic analysis of and key to
      species of taeniacanthodes.
AB  - Taeniacanthodes dojirii n. sp. (Copepoda: Poecilostomatoida: Taeniacanthidae) is
      described from adult female specimens collected from the body surface of Cortez
      electric rays Narcine entemedor (Torpediniformes, Narcinidae), captured at
      several locations in the Gulf of California. Taeniacanthodes dojirii is
      distinguished from its congeners, as well as from other members of
      Taeniacanthidae, by possessing unimerous fifth legs. A cladistic analysis of the
      3 known species of Taeniacanthodes resulted in a single most parsimonious tree
      (tree length = 18 steps, consistency index = 1) demonstrating that T. gracilis
      and T. haakeri, both parasites of benthic teleosts, are more closely related to
      each other than to the new species.

PMID- 12053976
TI  - Presidential address. Sex and schistosomes: an interesting biological interplay
      with control implications.

PMID- 12053977
TI  - Ecology and host specificity of laelapine mites (Acari: Laelapidae) of small
      mammals in an Atlantic forest area of Brazil.
AB  - Mesostigmatic mites of the Laelapinae Berlese, 1892 (Acari: Laelapidae) are
      nidicolous arthropods that commonly occur in the fur of Neotropical small
      mammmals. In this 2-yr study, the laelapine acarofauna associated with the small
      mammal community in an area of Atlantic forest on Ilha Grande, Rio de Janeiro
      State, was examined, including observations on patterns of host specificity, mite
      dispersal, ecology, and food habits. A total of 1,347 laelapines was sampled from
      the pelage of 6 species of small mammals (Marmosops incanus, Nectomys squamipes,
      Oryzomys russatus, Rhipidomys n. sp., Oxymycterus dasytrichus, and Trinomys
      dimidiatus), all of which occurred exclusively in monoxenous associations with
      their hosts. No evidence of a blood meal was observed in the gut of the mites.
      With the exception of the 2 species of Tur, mite populations on hosts were
      entirely or nearly restricted to adult females. These results, together with some
      morphological characteristics of laelapines, reinforce the hypotheses that
      Neotropical laelapine mites are not ectoparasitic, and that females disperse by
      phoresy.

PMID- 12053978
TI  - Comparing tolerance of Ichthyophthirius multifiliis and Tetrahymena thermophila
      for new cryopreservation methods.
AB  - Ichthyophthirius multifiliis is an obligate protozoan parasite of freshwater
      fishes that has a complex developmental cycle. It has not been successfully
      cryopreserved, so management studies are restricted to parasites obtained during
      outbreaks or perpetuated by passage in live fishes. To overcome this serious
      limitation, free-swimming I. multifiliis parasites were tested in a
      cryopreservation protocol routinely used for a related ciliate, Tetrahymena. In
      this protocol, I. multifiliis theronts retained infectivity for 3 days, although
      the protocol itself was ultimately lethal. Exposure of I. multifiliis and
      Tetrahymena thermophila to a battery of media and cryopreservative reagents
      showed that I. multifiliis was less hardy than T. thermophila and likely had
      significant biological and cytoskeletal differences. No combination of reagents,
      media, freezing rates, or dilution media permitted cryopreservation of I.
      multifiliis parasites that could then undergo development or infect fish.
      However, a vitrification protocol was formulated using Ficoll, 1,2-propanediol,
      and N,N-dimethylacetamide from which intact cryopreserved theronts with some
      motility were recovered. Understanding the effects of these reagents may lead to
      both a cryopreservation method for I. multifiliis and to improved understanding
      of the biology of ciliates.

PMID- 12053979
TI  - Parasitic infection and developmental stability: fluctuating asymmetry in
      Gammarus pulex infected with two acanthocephalan species.
AB  - Several studies have reported a negative association between developmental
      stability and parasitic infection. However, the host-parasite associations
      examined so far consist only of a limited number of parasite taxa, and
      developmental stability was appraised on definitive hosts. The present study
      examines the association between infection by 2 acanthocephalan parasites.
      Pomphorhynchus laevis and Polymorphus minutus, and the developmental stability of
      their common intermediate host Gammarus pulex. Developmental stability was
      estimated from the fluctuating asymmetry (FA) levels of 6 morphological traits. A
      positive association was found between FA and infection. Infected gammarids
      tended to be more asymmetrical than the noninfected ones for an index generated
      by combining FA scores from 2 characters out of the 6 studied, even though no
      significant relationships were found between FA levels and parasitic loads. The
      simultaneous presence of both acanthocephalan species in the same host seems to
      be associated with increased FA levels of gammarids, but this trend was not
      statistically significant. For the same characters, males exhibited higher levels
      of FA than females.

PMID- 12053980
TI  - Intestinal helminth infections are associated with increased incidence of
      Plasmodium falciparum malaria in Thailand.
AB  - In a prospective study of the total population of 5 hamlets on the western border
      of Thailand, all subjects were screened for helminth infections; during the
      following year, the incidence of malaria was recorded. Patients were not treated
      for helminth infections. Among 731 villagers, helminth-infected subjects were
      more likely to develop falciparum malaria during the following year (adjusted
      risk ratio 2.24, range 1.4-3.6; P = 0.001). The risk of developing falciparum
      malaria increased with the number of helminth species (P =0.036). Whereas in
      other studies helminths were associated with protection from severe complications
      of malaria, it seemed here that helminth-infected patients were more likely to
      develop malaria. It is suggested that a helminth-mediated Th2 shift may have
      complex consequences on malaria, decreasing antisporozoite immunity, but
      protecting against severe malaria.

PMID- 12053981
TI  - Plasmodium falciparum and P. vivax gametocyte-specific exoantigens stimulate
      proliferation of TCR gammadelta+ lymphocytes.
AB  - Immune modulation of Plasmodium vivax and P. falciparum gametocytes occurs over
      the course of erythrocytic infection. The response is linked to proliferative and
      inflammatory responses, which may be stimulated by stage-specific gametocyte
      proteins. Stage-specific exoantigens were purified from supernatants of P.
      falciparum and P. vivax gametocyte cultures, and either primary or secondary
      postinfection lymphocytes were stimulated for proliferation. Five of 25
      exoantigens purified from P. falciparum gametocyte cultures and 6 of 28
      exoantigens isolated from P. vivax were gametocyte stage specific. Metabolic
      labeling of soluble P. falciparum gametocyte proteins confirmed synthesis and
      secretion of 5 stage-specific exoantigens, with molecular masses of 118, 62, 52,
      37, and 33 kDa. Purified gametocyte exoantigens within the range of 50 to 100 kDa
      stage-specifically stimulated proliferation of lymphocytes from postprimary P.
      falciparum infections, and from postprimary and secondary P. vivax infection
      patients with homologous purified exoantigens. T-cell receptor (TCR)gammadelta+,
      and CD3+ CD8+ and CD3+ CD4- CD8- T cells were specifically upregulated from P.
      falciparum primary- and P. vivax secondary-infection lymphocytes, respectively,
      using gametocyte stage-specific exoantigens. CD25+ was the major activation
      marker expressed by CD3+ and gammadelta T cells when stimulated with gametocyte
      exoantigens. None of the T cell markers was significantly upregulated using
      gametocyte stage-specific exoantigens with primary-infection P. vivax
      lymphocytes.

PMID- 12053983
TI  - Characteristics of the haemoproteid community in an expanding white-winged dove
      population.
AB  - The haemoproteid community of 171 eastern white-winged doves (Zenaida asiatica
      asiatica) from the expanding Texas population was examined using thin blood
      smears. During summer 1997, heart blood was taken from doves within their
      historical breeding range (Lower Rio Grande Valley of Texas), an intermediate
      region (San Antonio and surrounding area), and the new breeding periphery (north
      central to southeast Texas). Two species were found: Haemoproteus columbae and
      Haemoproteus sacharovi. Infracommunities rarely occurred in heart blood, as only
      20 of 132 infected doves demonstrated gametocytes of both species. Overall
      prevalence of H. columbae and H. sacharovi was 77 and 15%, respectively.
      Prevalence of H. columbae was higher in the Lower Rio Grande Valley (LRGV) and
      intermediate regions than at the periphery, higher in adults than juveniles, and
      similar between males and females. Prevalence of H. sacharovi was lower in the
      LRGV than intermediate and peripheral regions, similar between juveniles and
      adults, and higher in females than males. Mean density of H. columbae and H.
      sacharovi was 15.9 +/- 2.7 and 0.3 +/- 0.1 (mean +/- SE per 3,000 erythrocytes),
      respectively. Overall mean abundance of H. columbae and H. sacharovi was 12.2 +/-
      2.2 and 0.04 +/- 0.02, respectively. Mean abundance of H. columbae was higher in
      the LRGV and intermediate regions than at the periphery and was similar between
      host age and between host sex; H. sacharovi was similar among regions, host age,
      and host sex. This study emphasizes the importance of using prevalence, density,
      and abundance data to assess haemoproteid community structure and pattern.

PMID- 12053982
TI  - The experimental infection of pigs with different numbers of Taenia solium eggs:
      immune response and efficiency of establishment.
AB  - Three of 4 pigs inoculated with 10 eggs of Taenia solium became infected. In
      those pigs infected with larger numbers of eggs, all became infected. Specific
      antibodies against the metacestodes were found in serum at day 30 postinoculation
      (PI) in animals that received 1,000 or more eggs and at day 60 in those that
      received 10 or 100 eggs. The concentration and diversity of antibodies increased
      up to the day of death in pigs that received 10,000 or 100,000 eggs. All pigs
      infected with 1,000 or more eggs developed antibodies, but only 40% and 75% of
      pigs that received 10 and 100 eggs, respectively, developed antibodies.
      Metacestodes were found in the muscles of 23 of the 27 infected animals. In 35.7%
      of the pigs that received 1,000 or more eggs, metacestodes were also found in the
      brain. Most of the metacestodes found in pigs infected with 10 or 100 eggs were
      caseous, whereas in pigs infected with 1,000 or more eggs the majority of
      metacestodes were vesicular. This study shows that the severity of T. solium
      infection and the possible regulation of the immune system-evasion mechanisms
      depend on the number of metacestodes that succeed in establishing themselves and
      remain vesicular.

PMID- 12053984
TI  - Acanthocephalans from crabs in the southeastern U.S., with the first intermediate
      hosts known for Arhythmorhynchus frassoni and Hexaglandula corynosoma.
AB  - Cystacanths of Hexaglandula corynosoma were discovered in the fiddler crabs Uca
      spinicarpa and Uca rapax collected in Mississippi and Florida. Adults were
      present in yellow-crowned night herons, Nyctanassa violacea, collected in
      Florida. Cystacanths are very similar to adults, varying only in size and state
      of development. This is the first record of H. corynosoma from the United States
      and the first record of an intermediate host for any species of the genus.
      Cystacanths of Arhythmorhynchus frassoni were present in U. rapax from Florida.
      The proboscis size, shape, and armature of the cystacanths are identical to those
      of adults from clapper rails (Rallus longirostris) collected in several
      southeastern states. This is the first report of an intermediate host for A.
      frassoni. Profilicollis altmani cystacanths were collected from mole crabs
      (Emerita talpoida) at Atlantic Beach, North Carolina. These specimens, together
      with adults obtained from shore birds in Louisiana and Mississippi, are
      consistent with the view that P. altmani, Profilicollis kenti, and Profilicollis
      texensis are synonyms, with P. altmani having nomenclatural priority.

PMID- 12053985
TI  - Associations between Trichinella species and host species in Finland.
AB  - Examination of 627 wild animals--raccoon dogs (Nyctereutes procyonoides), red
      foxes (Vulpes vulpes), European lynxes (Lynx lynx), brown bears (Ursus arctos),
      wolves (Canis lupus), and badgers (Meles meles)--revealed Trichinella spp. The
      prevalence varied according to geographical region of Finland (north; southwest,
      SW; and southeast, SE) and was the highest among lynxes (70%, SW). The risk of
      trichinellosis was higher in the SE (odds ratio, OR, 19.4) and SW regions (OR
      14.3), as compared with the northern region (OR 1), with no difference between
      the former 2 regions. Foxes (OR 2.1) and lynxes (OR 1.9) had a higher risk than
      raccoon dogs (OR 1) of being infected. The distribution of different Trichinella
      species was evaluated in 87 wild and domestic mammals by multiplex polymerase
      chain reaction. Trichinella spiralis was detected more often in domestic and
      synanthropic animals than in sylvatic hosts. Trichinella nativa was detected only
      in wildlife. Trichinella pseudospiralis was found both in sylvatic and
      synanthropic hosts. Trichinella britovi was detected only in mixed infections
      with other Trichinella species. The raccoon dog was the sole host for all 4
      Trichinella species and also carried the most intense infections.

PMID- 12053986
TI  - Prevalence, geographic distribution, and fitness effects of Microphallus turgidus
      (trematoda: Microphallidae) in grass shrimp (Palaemonetes spp.) from coastal
      Georgia.
AB  - Grass shrimp, Palaemonetes pugio Holthuis and P. vilgaris (Say), were collected
      at 11 localities along the coast of Georgia and surveyed for digenetic trematode
      metacercariae. The effect of trematode infection on grass shrimp fitness was also
      examined. Microphallus turgidas (Leigh) was the only trematode observed. The
      prevalence of metacercarial cysts of this parasite in P. pugio (75%) was higher
      than in P. vulgaris (24%), as were the mean intensity, abundance, and population
      density (no. cysts/cm host body length) of the parasite. Infected shrimp were
      found at every collection locality and parasite prevalence and density were
      greatest in P. pugio from higher salinity localities (> or = 20 parts per
      thousand [ppt]). There was no relation between host body size and parasite
      density in P. vulgaris, and parasite density increased with host body size in P.
      pugio, suggesting that the parasite does not affect host survival. There was no
      relation between parasite density and shrimp egg mass, but nonovigerous female P.
      pugio were more heavily infected than ovigerous ones. In addition, 1 metacercaria
      of M. turgidus in each of 2 specimens of P. vulgaris was parasitized by the
      haplosporidian Urosporidium crescens De Turk. This represents a new shrimp host
      record for this hyperparasite.

PMID- 12053987
TI  - Assessment of domestic goats as a patent host of Elaphostrongylus cervi.
AB  - A study was undertaken to determine whether domestic goats can serve as patent
      hosts of Elaphostrongylus cervi under natural or experimental conditions. Three
      hundred and two fecal samples from 124 domestic goats raised outdoors in New
      Zealand, where E. cervi is enzootic, were tested for nematode larvae by the
      Baermann method. All samples were negative for E. cervi dorsal-spined larvae.
      Twenty juvenile male Nubian and Saanen goats obtained locally were assigned
      randomly to 5 dosage groups and were orally administered 5, 15, 35, 65, or 125
      third-stage larvae of E. cervi, respectively. Two yearling female red deer
      (Cervus elaphus elaphus) each received 35 or 65 third-stage larvae as positive
      controls, and 2 uninoculated juvenile male goats served as negative controls.
      Fecal Baermann testing of pooled samples from the inoculated goats was conducted
      weekly for the first 80 days postinoculation (DPI) and daily thereafter until 250
      DPI. No dorsal-spined larvae were recovered. One goat that had received 15 third
      stage larvae displayed a mild transient posterior ataxia suggestive of
      cerebrospinal elaphostrongylosis. Gross postmortem examination did not reveal any
      direct evidence of nematodes in any of the goats, and only a few minor lesions
      were present. Histologically, these lesions were consistent with a parasite
      etiology. Histological evaluation of grossly normal lumbar and sacral spinal cord
      from 2 goats that had each received 125 third-stage larvae revealed eosinophilic
      meningoencephalitis and leukomyelitis, respectively, suggestive of the presence
      of parasites in the central nervous system. The 2 positive control red deer
      became patent with dorsal-spined larvae consistent with E. cervi at 131 DPI.
      These findings suggest that goats, at least those breeds utilized in this study,
      are not suitable patent hosts for E. cervi.

PMID- 12053988
TI  - Decreased hemoglobin concentrations, hyperparasitemia, and severe malaria are
      associated with increased Plasmodium falciparum gametocyte carriage.
AB  - To determine factors influencing gametocyte carriage, a cross-sectional study was
      conducted among 512 patients admitted for Plasmodium falciparum malaria. After
      adjustments for potential confounders, hemoglobin concentrations were lower in
      gametocyte carriers 10.5 (+/-2.5) than in patients without gametocytes 12.5 (+/
      2.3) (P < 0.0001). Hemoglobin concentrations were negatively correlated with peak
      gametocyte counts (Spearman's p = -0.37, P < 0.0001) and gametocyte carriage
      durations (Spearman's p = -(0.30, P < 0.0001). Adjustments for the duration of
      the malaria episode and other potential confounders did not alter the association
      (P < 0.0001). After adjustment for potential confounders, the median asexual
      parasitemia was higher in patients with gametocytes than in patients without
      gametocytes (P = 0.003). Severe malaria cases were more likely to have
      gametocytes (65%) than malaria with hyperparasitemia (38%) or mild malaria (31%)
      (P = 0.0001). These findings suggest that events surrounding anemia and tissue
      hypoxia stimulate Plasmodium falciparum gametocytogenesis.

PMID- 12053989
TI  - Comparison of nodulisporic acid analogs in a Lucilia sericata in vitro assay and
      a Ctenocephalides felis membrane feeding system.
AB  - A medicinal chemistry program on the nodulisporic acid chemical class, guided by
      an artificial membrane flea-feeding assay, has recently identified permissive and
      nonpermissive regions of the pharmacophore for exploitation against fleas. This
      pathway was validated when several promising compounds from this program were
      administered orally to dogs at 15.0 mg/kg and found to have >90% flea activity
      for 2 wk. To determine if a surrogate insect assay would have provided the same
      guidance, a nodulisporic acid analog series was examined in both a Lucilia
      sericata larval assay and an artificial membrane flea-feeding assay using
      Ctenocephalides felis. Results from both insect assays were concordant in that
      even subtle chemical modification or substitution to the left-hand side of the
      nodulisporic acid pharmacophore resulted in substantial loss of insecticidal
      activity. Both assays were also in general agreement that the only modifications
      to the pharmacophore that did not result in loss of activity occurred to the C-8
      side chain on the right-hand side of the molecule. Although there was good
      agreement between the 2 assays on the general regions of the pharmacophore, there
      was variance on individual compounds in the mono- and disubstituted amide series
      from the C-8 side chain. For example, the L. sericata assay showed several
      analogs from this subclass to possess similar activity to the parent acid,
      whereas the membrane assay indicated superior activity against fleas relative to
      the same parent. Consequently, although there was substantial general agreement
      between the assays, it was concluded that finer optimization of a lead compound
      should be done against the target parasite, even if it is ex vivo, as early as
      possible in a medicinal chemistry program.

PMID- 12053990
TI  - Partial characterization of a tapeworm-secreted signal factor inducing sustained
      spike potentials in the smooth muscle of the rat small intestine.
AB  - The rat tapeworm Hymenolepis diminuta alters the myoelectric activity of the
      small intestine. To determine if secreted factors from the tapeworm are
      responsible for these alterations of intestinal smooth muscle activity, tapeworm
      conditioned medium (TCM) obtained from in vitro culture was infused via an
      indwelling cannula into the duodenum of an uninfected rat. Myoelectric recordings
      were analyzed for sustained spike potentials (SSP) and repetitive bursts of
      action potentials (RBAP), the previously characterized tapeworm modifications of
      the normal interdigestive myoelectric pattern. Results indicated that TCM
      initiated SSP, but not RBAP in the intestine of the uninfected rat. The SSP
      inducing signal factor activity, present in TCM, was retained after boiling,
      prolonged freezing, proteinase treatment, and passage through a 10-kDa exclusion
      filter. The signal factor was soluble in the aqueous phase on lipid extraction.
      It was concluded that the SSP-inducing signal factor is a nonproteinaceous, heat
      resistant, low-molecular weight, water soluble molecule.

PMID- 12053991
TI  - Distribution of schistosome infections in molluscan hosts at different levels of
      parasite prevalence.
AB  - Biomphalaria glabrata snails infected with Schistosoma mansoni were collected
      during consecutive seasons from a site in Brazil known to have a very high
      percentage of infected snails. Schistosoma mansoni cercariae from single snails
      were used to infect individual mice, and the recovered adult worms were
      genetically assessed using a mtVNTR marker. The number of unique parasite
      genotypes found per snail was compared to expected abundance values, based on the
      infection prevalence at the site, to determine the distribution of S. mansoni
      infections within the snail population. The observed distributions and those from
      previous studies were used to examine the relationship between schistosome
      prevalence and aggregation across a wide range of prevalence values. Our analysis
      showed that prevalence was inversely related to the degree of parasite
      overdispersion, and at high prevalence, S. mansoni infections were randomly
      distributed among snails.

PMID- 12053992
TI  - Polyphasic typing of Cryptosporidium baileyi: a suggested model for
      characterization of cryptosporidia.
AB  - The present study was undertaken to characterize the oocyst morphology, host
      specificity, organ location, virulence, and sequences of the small subunit
      ribosomal RNA, 70-kDa heat shock protein, and oocyst wall protein genes of
      Cryptosporidium baileyi, and to compare this strain with other Cryptosporidium
      species. This study also aims to serve as a model for polyphasic (phenetic and
      genetic) characterization of Cryptosporidium species and strains. On the basis of
      these results, further genetic and phenetic characterization of an avian isolate
      is needed if the difference between the length or width, or both, of oocysts of
      an isolate and of C. baileyi is > or = 10% or if the difference between the
      oocyst shape index of the isolate and of C. baileyi is > or = 3% (or both). The
      isolate is infectious for mammals or lower vertebrates, or the host range is
      narrow, i.e., infectious only for some bird species; after oral or intratracheal
      inoculation, the parasites are not located in the cloaca and in the bursa of
      Fabricius or the respiratory tract; clinical disease or weight gain reduction can
      be observed after oral inoculation; the genetic distance for the examined gene
      between C. baileyi and the isolate is similar in magnitude to that observed
      between most closely related Cryptosporidium species.

PMID- 12053993
TI  - Ultrastructural study of the early development and localization of Loma salmonae
      in the gills of experimentally infected rainbow trout.
AB  - The early ultrastructural stages of Loma salmonae were studied in the gills of
      experimentally infected rainbow trout. No parasitic stages were identified during
      the first 2 wk of the infection. By week 3 postexposure (PE), uninucleate and
      binucleate meronts were recognized within host cells (no xenomas) associated with
      the capillary channels of secondary lamellae and lamellar arteries. An
      inflammatory reaction was absent. In secondary lamellae, infected cells were
      isolated from the capillary lumen, and some were recognized as pillar cells. In
      lamellar arteries, infected cells were localized beneath the endothelium and not
      in the lumen. Inflammatory reaction and destruction of parasites inside blood
      cells in the lumen of secondary lamellae were observed by week 4 PE. Three
      hypotheses, i.e., isolation, internalization, and evasion, are proposed to
      explain the localization of the infected cells in the gills. It is concluded that
      meronts are the earliest parasitic stage observed by week 3 PE, pillar cells are
      secondarily infected by phagocytosis of infected cells in the blood, endothelial
      cells of gills are not infected, and inflammatory response to the parasite starts
      by week 4 PE.

PMID- 12053994
TI  - Allele-specific PCR for the beta-tubulin codon 200 TTC/TAC polymorphism using
      single adult and larval small strongyle (Cyathostominae) stages.
AB  - It has been shown that benzimidazole (BZ) resistance in sheep gastrointestinal
      nematodes is linked with an increase in beta-tubulin codon 200 tyrosine
      expressing alleles in the resistant parasite populations. Here, an allele
      specific PCR has been developed for the discrimination of the TAC/TTC
      polymorphism in the beta-tubulin 200 codon of small strongyles. One reverse
      primer was used in 2 separate amplifications with 1 of 2 forward primers that
      differed only in their final 3' nucleotide. The primers flank a facultative
      intron/exon. Therefore, the amplified fragments are either 251 or 308 bp in size,
      depending on the presence or absence of the intron in individual worms.
      Amplification of genomic DNA isolated from single adult small strongyles from a
      set of 7 species consistently generated allele-specific products. Three worms
      each of the following species were used: Cylicocyclus nassatus, Cylicocyclus
      insigne, Cylicocyclus elongatus, Cylicocyclus radiatus, Cyathostomum pateratum,
      Cyathostomum catinatum, and Cyathostomum coronatum. PCR with DNA isolated from
      single larvae also reproducibly generated specific fragments. This method might
      be applied for the future assessment of allele frequencies in susceptible and
      resistant populations to further investigate the mechanism of BZ-resistance in
      small strongyles.

PMID- 12053995
TI  - Fertility insurance and the sex ratios of malaria and related hemospororin blood
      parasites.
AB  - The sex ratio (z*; proportion of gametocytes that are male) of malaria and
      related hemospororin blood parasites has been predicted to be related to the
      inbreeding rate (f) by the simple equation z* = (1 - f)/2. Although there is some
      empirical support for this prediction, there are several cases where the sex
      ratio is less female biased or more variable than expected. Here, we present a
      theoretical model that may be able to explain some of these discrepancies. We
      show that if low gametocyte densities lead to a danger that female gametes may
      not encounter any male gametes, then natural selection favors a less female
      biased sex ratio as a form of 'fertility insurance' to ensure that female gametes
      are mated. This model can be applied to a number of situations. In particular,
      (1) empirical data suggest that the number of gametocyes per blood meal can be
      low enough to favor fertility insurance in some Plasmodium infections in humans
      and (2) our model predicts facultative shifting toward less-biased sex ratios in
      response to immune pressure that reduces gametocyte or gamete survival or
      mobility, consistent with some recent experimental data from Plasmodium species
      of birds and mice.

PMID- 12053996
TI  - Protective immunity induced by irradiated third-stage larvae of the filaria
      Acanthocheilonema viteae is directed against challenge third-stage larvae before
      molting.
AB  - Jirds (Meriones unguiculatus) were vaccinated with irradiated L3 third-stage
      larvae (L3) of Acanthocheilonema viteae, and the time required for killing of the
      challenge L3 was determined. The number of parasites recovered from vaccinated
      jirds was reduced to about 10% of the control values on the second day after
      challenge infection and later on. Histological studies revealed an eosinophil
      rich infiltrate containing macrophages, neutrophils, and mast cells in the
      vicinity of the L3 on day 2 after challenge and destruction of the worms by day 4
      after challenge. Ultrastructural studies confirmed these data and showed that
      eosinophils, macrophages, and mast cells were close to the L3 on day 2 after
      challenge. Flattening of the eosinophils onto the surface of the worms,
      degranulation of electron-dense material, and rupture of the L3 surface was
      observed on day 4 after challenge, followed by invasion of the inner of the worms
      by phagocytic cells. These data show that immune attack against the challenge L3
      in vaccinated jirds is initiated between the first and the second day after
      challenge and that killing occurs around the fourth day after challenge, before
      the worms undergo their first molt.

PMID- 12053997
TI  - Immune factors influencing the course of infection with Neospora caninum in the
      murine host.
AB  - This paper investigates the role of specific immune factors on the course of
      infection in genetic knockout (gko) mice infected with 3 different strains of
      Neospora caninum. Survival time and parasite persistence were examined in
      interferon-gamma (IFN-gamma), tumor necrosis factor receptor-2 (TNFR2),
      interleukin 10 (IL-10), beta 2 microglobulin (beta2M), and inducible nitric oxide
      synthase (iNOS2) gko or wild-type (wt) mice following infection with either
      pathogenic (NC-1 or NC-2) or attenuated (NCts-8) N. caninum strains. Infection
      with NC-1 was 100% lethal in IFN-gamma gko mice, as evidenced by mean survival
      times of 10-13 days, depending on the challenge dose used. TNFR2 and beta2M gko
      mice infected with NC-1 or NC-2 strain demonstrated partial susceptibility to
      disease, as evidenced by histopathology and survival curves. TNFR2 or beta2M gko
      mice were not susceptible to infection with NCts-8, on the basis of absence of
      pathology and lack of mortality. Lack of mortality and minimal histopathology
      scores demonstrated that NC-1, NC-2, and NCts-8 infections were avirulent in IL
      10 and iNOS2 gko mice. Adoptive transfer of immune cells from NCts-8 vaccinated
      normal syngeneic mice into IFN-gamma gko mice significantly (P < 0.05) prolonged
      mean survival times at all 3 challenge doses of NC-1 but failed to protect
      against mortality. Interestingly, there was a notable change in the tissue
      tropism of tachyzoites from the lung and brain in immunocompetent wt, TNFR2 gko,
      IL-10 gko, beta2M gko, and iNOS2 gko mice to the liver and spleen in IFN-gamma
      gko mice when challenged with N. caninum. On the basis of these results in gko
      mice, IFN-gamma is a critical cytokine in the host response against acute
      neosporosis.

PMID- 12053998
TI  - Association of IL-10 expression by mucosal lymphocytes with increased expression
      of Cryptosporidium parvum epitopes in infected epithelium.
AB  - The objective of this study was to determine whether changes in the ileal
      intraepithelial lymphocyte (TEL) phenotype and function occurred prior to
      development of diarrhea in Cryptosporidium parvum-infected calves. Calves were
      orally inoculated with 10(8) oocysts and maintained in enteric pathogen-free
      conditions until their use in experiments. Age-matched uninfected calves were
      used for comparisons. Ileal IELs were isolated and phenotyped to determine
      whether changes in lymphocyte population dynamics had occurred by 3 days
      postinoculation (PI). Ex vivo reverse transcriptase-polymerase chain reaction of
      messenger ribonucleic acid (mRNA) from IELs from infected calves was compared
      with controls to determine whether changes in cytokine expression had occurred by
      3 days PI. No significant changes in lymphocyte population dynamics were
      documented, however, IELs isolated from 4 out of 8 infected calves, but not from
      8 out of 8 control calves, expressed mRNA for interleukin-10 (IL-10). IL-10
      expression by IELs was associated with the expression of a significantly larger
      (P < 0.001) proportion (0.75) of monoclonal antibody-defined C. parvum epitopes
      within infected ileal epithelium, as compared with a much smaller proportion
      (0.30) of epitopes with IL-10 lymphocytes. The results suggest that a temporal
      association exists between the expression of IL-10 by ileal IELs and the
      expression of C. parvum antigens in infected calf epithelium prior to development
      of cryptosporidiosis.

PMID- 12053999
TI  - Seasonal occurrence, morphology, and observations on the life history of Gordius
      difficilis (Nematomorpha: Gordioidea) from southeastern Wisconsin, United States.
AB  - A total of 584 adult nematomorphs, Gordius difficilis, was collected from 2 man
      made ponds and their overflow stream in southeastern Wisconsin. Ponds were
      surveyed throughout the year, but all free-living worms were found during July
      August of 1996, July-September of 1997, and June-August of 1998. Overall sex
      ratio was male biased; however, sex ratio was variable during different months.
      Observations during 1998-2000 indicated that worms mated within 24-48 hr of
      emergence from their hosts and began laying eggs by mid-August, continuing until
      mid-October. Eggs with well-developed larvae were recovered during October and
      November. Encysted larval nematomorphs were recovered from aquatic and
      semiaquatic invertebrates (gastropods, earthworms, and insects), whereas
      developing hairworms were found in terrestrial European ground beetles
      Pterostichus melanarius. It is hypothesized that semiaquatic invertebrates may
      serve as intermediate/paratenic hosts in this system and are preyed upon by
      terrestrial carabid beetles, thus completing the life cycle. In addition,
      scanning electron microscopy observations of G. difficilis add previously
      unreported observations on intraspecific variation in body length, cuticle
      morphology, and gametes of this species. This is the first report of G.
      difficilis from Wisconsin as well as the first report of this species from P.
      melanarius and aquatic and semiaquatic invertebrates.

PMID- 12054000
TI  - Experimental infection of Anopheles farauti with different species of Plasmodium.
AB  - Studies were conducted to determine the susceptibility of Anopheles farauti to
      different species and strains of Plasmodium. Mosquitoes were infected by feeding
      on animals or cultures infected with different strains of P. vivax, P.
      falciparum, P. ovale, P. coatneyi, P. gonderi, P. simiovale, P. knowlesi, and P.
      brasilianum. Infections of P. vivax and P. coatneyi were transmitted via
      sporozoites from An. farauti to monkeys. Comparative infection studies indicated
      that An. farauti was less susceptible to infection than An. stephensi, An.
      gambiae, An. freeborni, and An. dirus with the Salvador I strain of P. vivax, but
      more susceptible than An. stephensi and An. gambiae to infection with the
      coindigenous Indonesian XIX strain.

PMID- 12054001
TI  - Baylisascaris procyonis (Nematoda: Ascarididae) larva migrans in free-ranging
      wildlife in Orange County, California.
AB  - Baylisascaris procyonis is well recognized as a cause of visceral (VLM), ocular,
      and neural (NLM) larva migrans in birds and mammals, including man. A study of
      the prevalence of larva migrans in free-ranging wildlife associated with raccoon
      latrines as well as a retrospective study of wildlife mortalities with
      neurological disease was conducted in 2000 in Orange County, California. Eighty
      seven birds of 18 species and 64 mammals of 8 species were found to have NLM or
      VLM or both. NLM clinical signs included convulsions, torticollis, opisthotonus,
      head-tilts, circling, ataxia, paralysis, and visual defects. NLM lesions were
      characterized by focally disseminated, frequently linear, "tracklike" areas of
      parenchymal degeneration with varying degrees of astrocytosis in the white matter
      of the cerebrum, cerebellum, brain stem, and spinal cord. Larvae were rarely
      found in these lesions but were rather isolated in the brain-spinal cord
      parenchyma. At least 1 larva was isolated by digestion from each case of NLM and
      identified as Baylisascaris sp., most likely B. procyonis. VLM lesions consisted
      of granulomatous reactions surrounding intact or degenerative larvae in the
      parenchyma of the liver, kidney, diaphragm, and, occasionally, the lymph nodes.
      This report broadens the range of species of wild birds and mammals that have
      been found to be susceptible to larva migrans caused by B. procyonis and
      reaffirms the importance of raccoon latrine sites as contaminative foci for
      wildlife.

PMID- 12054002
TI  - The "crowding effect" in the cestode Schistocephalus solidus: density-dependent
      effects on plerocercoid size and infectivity.
AB  - The occurrence of the crowding effect was demonstrated in plerocercoids of the
      cestode Schistocephalus solidus infecting threespine stickleback Gasterosteus
      aculeatus from Walby and Scout lakes, Alaska. Contrary to an earlier report,
      relatively large numbers of parasites (>3-4 plerocercoids) were observed to grow
      large enough in an intermediate host fish to become competent to infect and to
      mature in the definitive host under any of 3 assumed threshold values and 1
      scenario of graded sizes for parasite competency. In Walby Lake, intensity and
      host body mass were significant predictors of mean plerocercoid mass per host,
      whereas intensity, host body mass, and combined parasite index were significant
      predictors in Scout Lake. Slopes of equations expressing the relationship between
      mean parasite mass and intensity for both lakes were less than 1, implying that
      processes other than or in combination with simple resource limitation might be
      producing the observed crowding effect. The causal mechanism for the crowding
      effect could include exploitative competition, interference competition, and host
      immune response. There were significant differences in infection between the two
      lakes, including different distributions of parasite intensities among hosts and
      different expressions of the crowding effect; however, an explanation of the
      differences awaits further investigation.

PMID- 12054003
TI  - Patterns in size and shedding of Fasciola hepatica eggs by naturally and
      experimentally infected murid rodents.
AB  - Using samples collected on the island of Corsica, a comparative study was done of
      the morphometry of Fasciola hepatica eggs shed by cattle and by naturally and
      experimentally infected murid rodents (wild Mus musculus and Rattus rattus and
      Rattus norvegicus Wistar laboratory strain). Eggs shed by murids are smaller in
      size than those shed by naturally infected cattle. A second study analyzed the
      number of F. hepatica eggs shed in murid feces at different time intervals, i.e.,
      months, days, and 6-hr periods, by the Kato-Katz technique. Both experimentally
      and naturally infected black rats (R. rattus) were used, and Wistar rats were
      experimentally infected and included for comparison. The present studies prove
      that black rats R. rattus are able to shed eggs independently from the liver
      fluke isolate and that egg shedding occurs throughout the life of this host
      species, uninterrupted during all the months analyzed in a 2-yr period. Moreover,
      the results suggest that this shedding is continuous, with eggs appearing in the
      feces daily. The results on egg shedding by wild black rats R. rattus reach their
      maximum shedding in spring and autumn and a maximum during twilight hr. These
      chronobiological patterns appear to favor parasite transmission, both seasonally
      and daily.

PMID- 12054004
TI  - Susceptibility of Psammomys obesus and Meriones tristrami to tachyzoites of
      Neospora caninum.
AB  - The susceptibility of Psammomys obesus (sand rat) and Meriones tristrami
      (Tristram's jird) to Neospora caninum was investigated by subcutaneous (s.c.) and
      intraperitoneal (i.p.) inoculation of 10-fold doses of culture-derived
      tachyzoites. Groups of 5 animals were inoculated with doses of 10-10(7) parasites
      via each route of inoculation. All but 2 of the sand rats inoculated with doses
      of 10-10(4) parasites succumbed to the infection by 7-18 days postinfection. All
      jirds inoculated with 10(7) tachyzoites succumbed by 5-16 days postinfection and
      those inoculated with 10(6) tachyzoites by 9-25 days. A considerable proportion
      of the jirds inoculated with 10-10(5) tachyzoites survived. Fibrinous peritonitis
      with ascites containing numerous tachyzoites was observed in the i.p.-inoculated
      sand rats and jirds that succumbed to the infection. In the jirds, tachyzoites
      were also found in pleural exudate. A considerable number (42.8%) of the jirds
      inoculated s.c. or i.p. exhibited neuromuscular symptoms, expressed in ataxia,
      head tilt, circling movement, and posterior paralysis. Seven successive passage
      of tachyzoites were achieved in sand rats with doses of 10(5) parasites and in
      jirds with doses of 10(7) parasites. All surviving jirds became seroconverted and
      were immune to lethal challenge.

PMID- 12054005
TI  - Atractis marquezi n. sp. (Nematoda: Atractidae) and a revision of Atractis
      dujardin, 1845, sensu Baker, 1987.
AB  - Atractis marquezi n. sp. from the large intestine of the tortoise Geochelone
      nigrita is described and illustrated. Atractis Dujardin, 1845, sensu Baker, 1987,
      is revised to contain only those atractids having a lagonoid spicule. The
      remaining species of Atractis sensu Baker, 1987, are assigned to Cyrtosomum,
      Pseudatractis, and Klossinemella. A. marquezi represents the 12th species to be
      assigned to this genus and is distinguished from other Neotropical species by the
      distribution pattern of caudal papillae of the male: 2 pairs precloacal, 2 pairs
      adcloacal, and 6 pairs postcloacal.

PMID- 12054006
TI  - Dicyema shorti n. sp. (phylum Dicyemida) from Octopus burryi (Mollusca:
      Cephalopoda: Octopodidae) in the Gulf of Mexico.
AB  - Nematogens and vermiform embryos of a new species of Dicyema are described from
      an octopus collected off Veracruz, Mexico. Dicyema shorti n. sp. is a small
      dicyemid species that rarely exceeds 500 microm in length. It is further
      characterized by the presence of 18 peripheral cells in the vermiform stages, a
      conical-shape calotte, and an axial cell that extends to the base of the propolar
      cells. Other stages in the life cycle of the parasite are not known. This is the
      first dicyemid to be described from Octopus burryi Voss. 1950, and also from both
      the southern Gulf of Mexico and the country of Mexico.

PMID- 12054007
TI  - New species of Dicyemennea (phylum: Dicyemida) in deep-water Graneledone
      (Mollusca: Cephalopoda: Octopoda) from the Antarctic.
AB  - Two new species of dicyemids are described from 2 species of deep benthic
      cephalopods, Graneledone antarctica and G. macrotyla, collected in the Southern
      Ocean south of the Antarctic Convergence. Dicyemennea bathybenthum n. sp. was
      found in G. antarctica. It is a medium-sized dicyemid whose length does not
      exceed 1,000 microm. The calotte is bluntly rounded or conical in small
      individuals, but the shape becomes discoidal in large individuals. Nematogens and
      vermiform embryos have 23 peripheral cells. An anterior abortive axial cell is
      present in vermiform embryos. Other stages in the life cycle were not observed.
      Dicyemennea dorycephalum n. sp. was found in G. macrotyla. It is a medium to
      large dicyemid that rarely exceeds 4,000 microm. The calotte is distinctly
      pointed, similar in shape to a spearhead. Vermiform stages typically have either
      25 or 27 peripheral cells. An anterior abortive axial cell is present in
      vermiform embryos. Infusoriform embryos have 37 cells, the refringent bodies are
      solid in composition, and 2 nuclei are present in each urn cell.

PMID- 12054008
TI  - Neoheterobothrium chilensis n. sp. (Monogenea: Diclidophoridae), a parasite of
      the bigeye flounder Hippoglossina macrops (Paralichthyidae: Pleuronectiformes)
      from northern Chile.
AB  - Neoheterobothrium chilensis n. sp. (Monogenea: Diclidophoridae) from the gills of
      the bigeye flounder Hippoglossina macrops (Paralichthyidae: Pleuronectiformes)
      from northern Chile (30 degrees 11'S, 71 degrees 51'W) is described and compared
      with the known species in the genus. Diagnostic characters include the position
      of the seminal receptacle, the number of hooks in the male copulatory organ, the
      number of testes, and the relative size of the clamp peduncles.

PMID- 12054009
TI  - Notomegarhynchus navonae n. gen. and n. sp. (Eucestoda: Tetraphyllidea), from
      skates (Rajidae: Arhynchobatinae) in the southern hemisphere.
AB  - Notomegarhynchus n. gen. (Eucestoda: Tetraphyllidea) is proposed to accommodate
      Notomegarhynchus navonae n. gen., n. sp. from Atlantoraja castelnaui in Mar del
      Plata, Argentina. Notomegarhynchus shetlandicum n. comb. from Bathyraja eatonii
      and B. maccaini in South Shetlands region, Antarctica, is a second species in the
      genus. Notomegarhynchus belongs to the Echeneibothriinae within the
      Phyllobothriidae. It can be distinguished from all other tetraphyllidean genera
      by the structure of the scolex in form of a massive myzorhynchus consisting of a
      proscolex and an apical organ, both of which are nonretractable and
      noninvaginable; in addition, there are 4 pedunculated and nonloculate acetabula.
      Notomegarhynchus shetlandicum is differentiated from N. navonae particularly in
      details of acetabular and myzorhynchus morphology, arrangement of testes, and
      shape of eggs. The inclusion of Notomegarhynchus in the Echeneibothriinae
      requires emendation of the diagnosis of the subfamily to include taxa possessing
      postvaginal testes. In addition, new terminology is proposed for distinct regions
      of the scolex.

PMID- 12054010
TI  - Unusual plasmodium malariae-like parasites in southeast Asia.
AB  - During malaria surveys in Myanmar, 2 peculiar forms of Plasmodium malariae-like
      parasites were found. The morphologies of their early trophozoite stages were
      distinct from that of the typical P. malariae, resembling instead that of
      Plasmodium vivax, var. minuta, reported by Emin, and Plasmodium tenue, reported
      by Stephens, both in 1914. Two polymerase chain reaction (PCR)-based diagnoses,
      which target the same regions in the small subunit ribosomal RNA (SSUrRNA) genes,
      indicated that these parasites were new variant forms of P. malariae and that
      they could be separated into 2 genetic types that correlated with the 2
      morphological types. Sequence analysis of the SSUrRNA and the circumsporozoite
      protein genes revealed that they were distinct both from each other and from
      other known P. malariae isolates and that the P. tenue-like type was closer to a
      monkey quartan malaria parasite, Plasmodium brasilianum. These results illustrate
      that the microscopic appearance of human P. malariae parasites may be more varied
      than previously assumed and suggest the value of molecular tools in the
      evaluation of malaria morphological variants.

PMID- 12054011
TI  - Two new species of Pseudohapladena yamaguti, 1952 (Digenea: Waretrematidae) from
      mugilid fish from the Taiwan Straits, China.
AB  - Two new species of Pseudohapladena Yamaguti, 1952 (Digenea: Waretrematidae) are
      described. Pseudohapladena megoorchis n. sp. was obtained from the intestine of
      Mugil engeli (Bleeker) (Mugilidae), and Pseudohapladena lizae n. sp. from the
      intestine of Liza carinatus (Cuvier and Valenciennes) (Mugilidae).
      Pseudohapladena megaorchis is the most closely related in general morphology to
      Pseudohapladena scatophagi Yamaguti, 1952, but differs from the latter in the
      position of the hermaphroditic sac, and in the nature and distribution of the
      vitellaria. Features of P. lizae distinguishing it from other species of the
      genus include the shorter uterus, which contains only 1 egg, and the lesser
      extent of the vitellaria.

PMID- 12054012
TI  - Phanurus oligoovus gen. et sp. nov. (Digenea: Waretrematidae) from Liza carinatus
      from the South China Sea.
AB  - The species Phanurus oligoovus gen. et sp. nov. is described from the intestine
      of Liza carinatus (Cuvier et Valencienne) from the South China Sea. From the
      general internal anatomy, it belongs to the Waretrematidae and is distinguished
      from the other known species of the Waretrematidae by the tail appendage. A new
      subfamily, Phanurunae, is proposed for the genus Phanurus.

PMID- 12054013
TI  - Reevaluation and emended diagnosis of Illiosentis and I. heteracanthus
      (Acanthocephala: Illiosentidae).
AB  - Information on putative synapomorphies was used to distinguish between
      Dollfusentis, Illiosentis, and Tegorhynchus. Members of Tegorhynchus and
      Illiosentis possess a thick padlike vestibular muscle on the inner posterior wall
      of the trunk of female worms. The 2 genera differ in that the proboscis of
      members of Illiosentis have ventral hooks in the posteriormost circle that are
      greatly enlarged and male worms have a heavy muscular sheath covering the
      urogenital duct, both of which are absent in members of Tegorhynchus. Based on
      these features, Illiosentis is formally reestablished, and the diagnosis of the
      genus is emended. Dollfusentis is characterized by members having vestibular
      muscles that are bandlike rather than padlike, normal-sized hooks in the poster
      ring of the proboscis, and a crescent of 6 large hooks on the ventral proboscis,
      separated posteriorly from the posteriormost ring of hooks. The heavy muscular
      sheath covering the urogenital duct is not present in male worms of species of
      Dollfusentis. Type specimens of D. heteracanthus, originally described as I.
      heteracanthus but later transferred from Illiosentis to Dollfusentis, and the
      material included in a recent redescription of D. heteracanthus possess the
      padlike vestibular muscle, greatly enlarged ventral proboscis hooks in the
      posteriormost circle, and heavy muscular sheath covering the urogenital duct that
      is characteristic of other members of Illiosentis and lack the features
      characteristic of the other species assigned to Dollfusentis. Thus, D.
      heteracanthus is removed from Dollfusentis and reinstated as I. heteracanthus.

PMID- 12054014
TI  - Spauligodon loboi n. sp. (Nematoda: Pharyngodonidae) parasite of Liolaemus spp.
      (Iguania: Liolaemidae) from northwestern Argentina.
AB  - Three-hundred and forty-nine specimens of Spauligodon loboi n. sp. (Nematoda,
      Pharyngodonidae) were found in the large intestines of 55 of 225 adult specimens
      representing 5 species of Liolaemus collected in 11 localities of northwestern
      Argentina. Prevalence of infection was 24% (mean intensity = 6.3 +/- 3.4, range =
      2-28). Spauligodon loboi n. sp. differs from other neotropical species in that
      the filamentous portion of the tail of males is spiny, whereas that of females is
      smooth. A key to the species of Spauligodon in the Neotropical Realm is provided.

PMID- 12054015
TI  - Species of Mediorhynchus (Acanthocephala: Gigantorhynchidae) in Australian birds
      with the description of Mediorhynchus colluricinclae n. sp..
AB  - Four species of Mediorhynchus are identified from Australian birds. New locality
      records are given for Mediorhynchus alecturae (Johnston and Mawson, 1947) Golvan,
      1962 and new host and locality records for M. corcoracis Johnston and Edmonds,
      1951. Mediorhychus grandis has been reported from Australian hosts, but this
      record could not be verified. Two females from Acanthogenys rufogularis and the
      anterior portion of a single female from a "gull" had characters of proboscis
      armature, lemnisci, and eggs that precluded them being assigned to any of the
      presently known species of Mediorhynchus. Mediorhynchus colluricinclae n. sp. was
      found in pomatostomatids from South Australian localities. A high degree of host
      specificity is recorded for M. corcoracis and M. colluricinclae. Selection of
      specific dietary items may be one filter that influences the degree of host
      specificity encountered.

PMID- 12054016
TI  - Description of Bucephalus anguillae n. sp. (Trematoda: Bucephalidae), a parasite
      of the eel Anguilla anguilla (Anguillidae) from a brackish water lagoon of the
      Adriatic Sea.
AB  - The digenetic trematode Bucephalus anguillae n. sp. is described from the
      intestine of eel, Anguilla anguilla L., originating from a brackish water fish
      farm on the Italian coast of the Adriatic Sea. The new taxon is 1 of 12
      Bucephalus species characterized by an anterior rhynchus surrounded by 7
      tentacular appendages, each when fully protruded with 2 prongs. Scanning electron
      microscopy reveals, for the first time in a Bucephalus species, the crescent
      shaped, unspined field located between the rhynchus and the dorsal tentacles. A
      comparison of B. anguillae n. sp. with 11 congeneric species revealed its
      remarkable similarity with B. polymorphus Baer, 1827; however, the new species
      has a larger cirrus sac, larger pharynx, vitelline gland fields not extending the
      level of pharynx, ovary located in the pharyngeal area rather than fairly
      posterior to pharynx, smaller testes, relatively wider rhynchus, and tegumental
      armature comprising slightly larger spines. Multivariate discriminant analyses
      confirmed a differentiation of B. anguillae from populations of B. polymorphus;
      the combination of 4 variables, namely cirrus sac length, pharynx width, cirrus
      sac width, and rhynchus width yielded a total separation of compared species.

PMID- 12054017
TI  - Molecular phylogeny and evolutionary relationships of Cryptosporidium parasites
      at the actin locus.
AB  - To further validate previous observations in the taxonomy of Cryptosporidium
      parasites, the phylogenetic relationship was analyzed among various
      Cryptosporidium parasites at the actin locus. Nucleotide sequences of the actin
      gene were obtained from 9 putative Cryptosporidium species (C. parvum, C.
      andersoni, C. baileyi, C. felis, C. meleagridis, C. muris, C. saurophilum, C.
      serpentis, and C. wrairi) and various C. parvum genotypes. After multiple
      alignment of the obtained actin sequences, genetic distances were measured, and
      phylogenetic trees were constructed. Results of the analysis confirmed the
      presence of genetically distinct species within Cryptosporidium and various
      distinct genotypes within C. parvum. The phylogenetic tree constructed on the
      basis of the actin sequences was largely in agreement with previous results based
      on small subunit rRNA, 70-kDa heat shock protein, and Cryptosporidium oocyst wall
      protein genes. The Cryptosporidium species formed 2 major clades; isolates of C.
      andersoni, C. muris, and C. serpentis formed the first major group, whereas
      isolates of all other species, as well as various C. parvum genotypes, formed the
      second major group. Intragenotype variations were low or absent at this locus.

PMID- 12054018
TI  - Effects of ivermectin and albendazole against Anisakis simplex in vitro and in
      guinea pigs.
AB  - The activity of ivermectin and albendazole against larval Anisakis simplex was
      tested in vitro and in experimentally infected guinea pigs. Before drug exposure
      the medium for half of the larvae was adjusted to pH 2.0 with 1 N HCl, whereas
      the other half was held at pH 7.0. To these solutions, ivermectin was added to
      full concentrations of 1, 2, 5, 10, 50, 100, or 200 microg/ml, and for
      albendazole, 300, 400, and 500 microg/ml. Animals from group I were given 0.1 ml
      of 1% (3.3 mg/kg) ivermectin, whereas guinea pigs from group II were each given 5
      7 mg (16.6-23.3 mg/kg) of albendazole orally. The efficacy of both drugs against
      L, A. simplex was high in vitro and in vivo against the larvae in different
      organs of guinea pigs.

PMID- 12054019
TI  - Dimethicone barrier cream prevents infection of human skin by schistosome
      cercariae: evidence from Franz cell studies.
AB  - One approach to the prevention of schistosomiasis is the use of topical
      formulations to inhibit cercarial penetration of skin. A number of formulations
      containing either cercaricidal ingredients or components designed to inhibit
      penetration have been studied, but with variable results. Such studies have
      rarely considered the persistence of inhibitory effects through time, and to
      date, there have been no systematic investigations of barrier formulations. The
      aim of this study was to use Franz cells to investigate the effect of such
      barrier creams on the penetration of S. mansoni cercariae into human skin. The
      results show that a single application of a barrier cream based on dimethicone
      offers a high level of protection against penetration that is sustained for at
      least 48 hr.

PMID- 12054020
TI  - Presence of genital spines in a male Corynosoma cetaceum Johnston and Best, 1942
      (Acanthocephala).
AB  - We collected 83 females and 80 males of Corynosoma cetaceum from 2 common
      dolphins, Delphinus delphis, collected in northern Patagonia (Argentina). Worms
      were most similar to specimens collected in other South American localities.
      However, 1 male had 2 spines adjacent to the genital pore and isolated from the
      rest of body spines. This finding confirms the recent reassignment of C. cetaceum
      to Corynosoma. Absence of genital spines is suggested to be avoided as the sole
      criterion to exclude specimens from Corynosoma or Andracantha.

PMID- 12054021
TI  - First recovery of Schistosoma mansoni eggs from a latrine in Europe (15-16th
      centuries).
AB  - Schistosoma mansoni eggs were found in a latrine dated AD 1450-1550 in
      Montbeliard, France. This is the first record of intestinal schistosomiasis in
      archaeological material. Because the parasite has an African origin, its presence
      in Europe at that time may be due to African slaves. However, intestinal
      schistosomiasis has never been established in Europe.

PMID- 12054022
TI  - Dexamethasone inhibition of the cellular immune response of Drosophila
      melanogaster against a parasitoid.
AB  - Host larvae of Drosophila melanogaster injected with the eicosanoid biosynthesis
      inhibitor, dexamethasone, prior to parasitization by the wasp Leptopilina
      boulardi, exhibited significantly reduced rates of melanotic encapsulation in
      comparison with control and saline-injected larvae. The results of this
      investigation suggest that prostaglandins and other eicosanoids are involved as
      cell-signaling molecules in the hemocytic encapsulation reaction of D.
      melanogaster larvae.

PMID- 12054023
TI  - Prevalence of Neospora caninum antibodies in dogs from dairy cattle farms in
      Parana, Brazil.
AB  - Serum samples from 134 dogs from 22 cattle dairy farms in the northern region of
      Parana State, Brazil, were tested for antibodies to Neospora caninum in an
      indirect fluorescent antibody test. Antibodies (> or = 1:50) to N. caninum were
      found in 29 (21.6%) of the 134 dogs, and seropositive dogs were found on 14
      (63.6%) of the 22 dairy cattle farrms. The antibody titers of dogs were 1:50 (3
      dogs), 1:100 (7 dogs), 1:200 (7 dogs), 1:400 (6 dogs), and > or = 1:800 (6 dogs).
      The low prevalence (9%) in < 1-yr-old dogs compared with the 2- to 3-fold higher
      prevalence in older dogs (17-29%) suggests postnatal exposure to N. caninum
      infection.

PMID- 12054024
TI  - Arthropod and helminth parasites of the wild guinea pig, Cavia aperea, from the
      Andes and the cordillera in Peru, South America.
AB  - As part of an ongoing research project concerning the diversity and distribution
      of parasites of Caviidae in South America, 143 wild guinea pigs (Cavia aperea)
      were collected from 3 localities in the Andean Highlands of Peru. Samples were
      collected between November 1996 and May 1999 and included representatives of
      arthropods, nematodes, and trematodes. Seven species of arthropods: Leptopsylla
      segnis (27.3%), Tiamastus cavicola (6.9%), Gliricola porcelli (55.2%),
      Hoplopleura alata (6.9%), Polyplax spinulosa (12.6%), Myobia musculi (1.4%), and
      Eutrombicula bryanti (49.6%); 4 species of nematodes: Capillaria hepatica (6.9%),
      Graphidioides mazzai (18.8%), Trichuris gracilis (3.5%), and Paraspirudera
      uncinata (37%); and a single trematode, Fasciola hepatica (4.2%), were
      identified.

PMID- 12054025
TI  - Seroepidemiology of Toxoplasma gondii infection among two mountain aboriginal
      populations and Southeast Asian laborers in Taiwan.
AB  - A seroepidemiological survey of Toxoplasma gondii infection among Atayal and
      Paiwan mountain aborigines and Southeast Asian laborers in Taiwan was assessed
      from February 1998 to July 2000 using a latex agglutination test. To determine
      risk factors for T. gondii infection among Taiwan aborigines, the consumption of
      raw meat and valley water were given particular attention in a self-administered
      questionnaire. The overall seroprevalence of T. gondii infection was 19.4% for
      Atayal, 26.7% for Paiwan, 42.9% for Indonesian, 14.7% for Thai, and 11.3% for
      Filipinos. No significant gender difference in seroprevalence was found among
      Atayals, Paiwans, Indonesians, and Filipinos (P > 0.05). In the Thai group,
      however, males had a higher seroprevalence than females (P < 0.001). Results of
      the multiple logistic regression analysis indicate a higher odds ratios (OR) with
      age in both aboriginal groups. In contrast, the OR was lower among older
      Indonesians and Thais. Those Atayals and Paiwans with a history of eating raw
      meat seemed more susceptible to T. gondii infection than those who had never
      consumed raw meat. Ethnically, a significant difference in seroprevalence was
      observed between Indonesians and Paiwans, Atayals, Thais, and Filipinos (P <
      0.001).

PMID- 12054026
TI  - Congenital infection with Schistosoma japonicum but not with Schistosoma bovis in
      sheep.
AB  - The present study investigated whether Schistosoma japonicum or Schistosoma bois
      could establish prenatally in lambs. Three ewes were exposed to S. japonicum by
      intramuscular injection of cercariae, and 3 ewes were exposed to S. bovis
      cercariae using the leg-emerging technique approximately 2 mo before delivery,
      and 1 age-matched pregnant ewe served as an uninfected control. The study lasted
      18-20 wk after infection, which was 8-9 wk after delivery. All 6 exposed ewes
      became infected with either S. bovis or S. japonicum. Eight lambs were borne by
      the 7 ewes, of which 1 (S. bovis exposed) was dead and 1 (S. japonicum exposed)
      died at delivery. Of the 3 S. japonicum-exposed lambs, 2 were found infected.
      Four lambs born of S. bovis-exposed ewes were negative. Despite having no worms,
      these 4 S. bovis-exposed lambs as well as the 1 negative S. japonicum-exposed
      lamb had, in contrast to the nonexposed control lamb, few, but distinct, liver
      granulomas dominated by eosinophils and giant cells with large central necrotic
      areas but with no remnants of eggs or worms. Hence, congenital infection was
      demonstrated in S. japonicum-infected lambs, but not in S. bovis-infected ones.

PMID- 12054027
TI  - Prevalence of antibodies to Neospora caninum in white-tailed deer, Odocoileus
      virginianus, from the southeastern United States.
AB  - Serum samples from 305 white-tailed deer (Odocoileus virginianus) from 14 states
      in the southeastern United States were examined for antibodies to Neospora
      caninum using a direct agglutination test. Positive agglutination titers were
      found in 145 (48%) of the white-tailed deer examined: 21 (7%) had titers of 1:25,
      92 (30%) had titers of 1:50, and 32 (10%) had titers of > or = 1:500. These
      findings that antibodies to N. caninum are common in white-tailed deer support
      the concept that a sylvatic cycle might exist for this economically important
      parasite of domestic cattle.

PMID- 12054028
TI  - Identical ITS-1 and ITS-2 sequences suggest Spiculopteragia asymmetrica and
      Spiculopteragia quadrispiculata (Nematoda: Trichostrongylidae) constitute
      morphologically distinct variants of a single species.
AB  - Sequences of ITS-1 and ITS-2 rDNA for adult males of Spiculopteragia asymmetrica
      and Spiculopteragia quadrispiculata in red deer (Cervus elaphus) were determined.
      They were found to be identical, suggesting that S. asymmetrica and S.
      quadrispiculata represent a single species and do not refute the concept of
      dimorphic species in the Spiculopteragia.

PMID- 12054029
TI  - Prevalence of Toxoplasma gondii antibodies in sera of domestic cats from
      Guarulhos and Sao Paulo, Brazil.
AB  - Antibodies to Toxoplasma gondii were determined in serum samples of 502 domestic
      cats from Brazil by the modified agglutination test (MAT), using formalin-fixed
      whole tachyzoites and mercaptoethanol. Antibodies (MAT > or = 1:20) were found in
      132 (26.3%) of 502 cats. With respect to origin, antibodies were found in 26.7%
      of 430 stray cats from Sao Paulo, 10% of 40 stray cats from Guarulhos, and 40.6%
      of 32 cats from a cat breeder in Sao Paulo. Antibody titers were: 1:20 in 10
      cats, 1:25 in 40 cats, 1:50 in 73 cats, and > or = 1:500 in 9 cats. Exposure
      rates of T. gondii in cats from Sao Paulo, Brazil are similar to that in domestic
      cats in North America.

PMID- 12054030
TI  - Distribution and prevalence of Echinococcus multilocularis in wild predators in
      Nebraska, Kansas, and Wyoming.
AB  - To further determine the distribution and prevalence of Echinococcus
      multilocularis in the central United States, 245 wild canids (125 red foxes, 120
      coyotes) and 33 bobcats were collected from Nebraska, Kansas, and Wyoming and
      examined for this parasite. Animals examined included 11 red foxes from the
      western panhandle of Nebraska; 5 red foxes and 30 coyotes from southern Nebraska;
      56 red foxes and 1 coyote from northeastern Nebraska; 20 red foxes, 63 coyotes,
      and 13 bobcats from northern Kansas; 2 red foxes, 26 coyotes, and 20 bobcats from
      southern Kansas; and 31 red foxes from east-central Wyoming. Of these, 27 of 72
      (37.5%) red foxes from Nebraska were positive, including 2 of 11 (18.2%) from the
      western panhandle and 25 of 56 (44.6%) from the northeastern part of the state.
      Mean intensity of infection was 282 worms (range, 1-5,150). New distribution
      records were established for E. multilocularis in western Nebraska as well as for
      several northeastern counties. These findings support previous estimates that the
      southernmost front of the parasite's range extends along the southern border of
      Wyoming, eastward through central Nebraska and central Illinois into Indiana and
      Ohio.

PMID- 12054031
TI  - Infection of Aotus and Saimiri monkeys with Plasmodium gonderi.
AB  - Attempts were made to infect 4 species of New World monkeys (Saimiri boliviensis,
      Aotus nancymai, A. vociferans, A. azarae boliviensis) with Plasmodium gonderi, a
      malaria parasite of African monkeys. Sporozoites were obtained from Anopheles
      dirus or A. stephensi mosquitoes that fed on an infected rhesus monkey (Macaca
      mulatta). Inoculation of sporozoites was by injection of dissected sporozoites by
      either the intravenous or intrahepatic routes, or by mosquito bite. Liver
      biopsies done 7 or 8 days after sporozoite inoculation showed that hepatocytes of
      all 4 species of these New World monkeys supported exoerythrocytic stages of P.
      gonderi, but daily blood film examination during a 60-day observation period
      failed to detect blood stages of the parasite.

PMID- 12054032
TI  - Negative influence of Gammarinema gammari (Nematoda) on the fecundity of
      Microphallus papillorobustus (Trematoda): field and experimental evidence.
AB  - The gammarid amphipod Gammarus insensibilis frequently harbors adult individuals
      of the ectoparasitic nematode Gammarinema gammari as well as metacercariae of the
      trematode Microphallus papillorobostus. After the demonstration in a previous
      study of a negative relationship between the abundance of these 2 parasites, the
      nature of the relationship between these 2 parasites was explored in more detail
      by studying, in the field and in the laboratory, the influence of nematode
      abundance on trematode fecundity. In gammarids collected in the field, a negative
      relationship between metacercarial fecundity and the number of co-occurring
      nematodes was found. By manipulating the nematode abundance in the laboratory, it
      was confirmed that G. gammari has a negative effect on egg production in M.
      papillorobustus.

PMID- 12054033
TI  - The impact of internalized homophobia on HIV preventive interventions.
AB  - A growing body of research implicates internalized homophobia--the
      internalization of society's antihomosexual sentiments by gay and lesbian people-
      as a factor contributing to HIV-related sexual risk behavior in gay and bisexual
      men. Although accumulating evidence links internalized homophobia and sexual risk
      behavior, no study has explored the impact of internalized homophobia on efforts
      to prevent these behaviors. This paper examines the effect of internalized
      homophobia on gay and bisexual men's awareness of participation in, and
      perceptions of programs offered by a community-based HIV prevention organization.
      In Study 1, 595 gay and bisexual men reported their levels of awareness of and
      participation in HIV prevention programming offered by one community
      organization. Internalized homophobia was negatively related to men's awareness
      of the services offered by the organization. However, among the men who were
      aware of at least one service, internalized homophobia did not further predict
      service utilization. Study 2 examined 89 gay and bisexual men who participated
      for a single session in a group-structured, community-based HIV preventive
      intervention. Pre- to immediate postintervention change in perceptions of condom
      use self-efficacy was inversely related to internalized homophobia. Internalized
      homophobia was also a significant negative predictor of the extent to which
      participants felt similar to and related well with other members of the group.
      Together, these findings suggest that internalized homophobia may pose multiple
      barriers to community-based HIV prevention efforts.

PMID- 12054034
TI  - Factors contributing to the survival of self-help groups.
AB  - Despite the growing utilization of self-help groups, there have been only a
      handful of studies that have examined the factors that contribute to their
      survival. The purpose of this study was to explore the factors that contribute to
      self-help group survival by examining their relationship with external sources
      (i.e., national and local self-help organizations, professionals) and group
      organizational characteristics (i.e., leadership diversification, recruitment,
      attendance at group meetings). Representatives from 245 active and 94 recently
      disbanded self-help groups were included in the analysis. Results indicated that
      the primary factors that discriminated between active and disbanded groups were
      the number of new people to attend a meeting, average group meeting attendance,
      length of existence, leadership diversification, outreach to potential group
      members, and support from national and local organizations. Results are discussed
      in terms of what national self-help organizations, self-help clearinghouses, and
      others who interact with self-help groups can do to empower and support them.

PMID- 12054035
TI  - The academic achievement of African American students during early adolescence:
      an examination of multiple risk, promotive, and protective factors.
AB  - This study examined the effects of multiple risk, promotive, and protective
      factors on three achievement-related measures (i.e., grade point average, number
      of absences, and math achievement test scores) for African American 7th-grade
      students (n = 837). There were 3 main findings. First, adolescents had lower
      grade point averages, more absences, and lower achievement test scores as their
      exposure to risk factors increased. Second, different promotive and protective
      factors emerged as significant contributors depending on the nature of the
      achievement-related outcome that was being assessed. Third, protective factors
      were identified whose effects were magnified in the presence of multiple risks.
      Results were discussed in light of the developmental tasks facing adolescents and
      the contexts in which youth exposed to multiple risks and their families live.

PMID- 12054036
TI  - Promotion of social change: a conceptual framework.
AB  - This paper argues for the need to advance promotion efforts and proposes a
      conceptual framework for promotion of social change. A brief review is presented
      of traditional frameworks for the prevention of mental and social disorders and
      the promotion of wellness and social competencies, with attention to the ways in
      which promotion of social change extends and departs from these frameworks. In a
      framework for promoting social change, we advocate for promoting dynamic
      processes within systems, rather than outcomes within individuals. Systems are
      viewed as flexible and capable of facilitating multiple adaptive pathways for
      individuals and groups. Promoting social change also involves careful attention
      to critical analysis, values, language, and contextual processes. Examples are
      discussed throughout to illustrate how these principles have been used in the
      past and can be implemented in future efforts to promote social change.

PMID- 12054037
TI  - Battered women's coping strategies and psychological distress: differences by
      immigration status.
AB  - People are rarely passive, and battered women are no exception. This study
      investigated the types of coping strategies women of Japanese descent (both Japan
      born and U.S.-born) chose and their perceived effectiveness in dealing with their
      partners' violence. Japan-born respondents were significantly less likely to use
      "active" strategies and perceived them to be less effective than did U.S.-born
      respondents For the Japan-born, the more effective they perceived "active"
      strategies, the higher their psychological distress, whereas the more effective
      they perceived "passive" strategies, the lower their psychological distress. In
      contrast, for the U.S.-born, the higher the perceived effectiveness of "active"
      strategies, the lower their psychological distress, and the perceived
      effectiveness of "passive" strategies had little effect on their psychological
      distress. The complex relationship between individuals' country of birth, the
      choice and perceived effectiveness of coping strategies, and psychological
      distress calls for increased attention to the role of culture in studies of
      coping and domestic violence.

PMID- 12054038
TI  - Implications of evidence-based practice for community health.
AB  - Evidence-based practice, developed in clinical medicine, is being applied to
      community health programs. Barriers to implementation of evidence-based practice
      noted in clinical medicine are likely to exist in community health settings and
      may be complicated by the nature of community health programs. These barriers
      include accessibility and availability of relevant data, social and political
      considerations of program decision-making, and conflicting expectations for
      evaluation research. This paper discusses barriers to both amassing evidence for
      practice and using evidence for decision-making in community health. The
      potentialfor conflict between practice goals set by evidence-based thinking and
      those set by community health organizations is also discussed. Implications for
      evaluations of community health programs are raised and recommendations for
      improving access to and use of evaluation information are made.

PMID- 12054039
TI  - Estimation of 14CO2 flux at soil-atmosphere interface and distribution of 14C in
      forest ecosystem.
AB  - To realize the dynamical behavior of 14C among exchangeable carbon reservoirs in
      terrestrial environment, a method for in situ determination of 14CO2 flux at soil
      atmosphere interface and a high flow rate CO2 sampler were developed. This method
      allowed us to collect integrated quantity of CO2 for determining 14C activity
      over an extended time period under environmental conditions with minimal site
      disturbance. The 14CO2 flux from ground surface was estimated to be 1.59 x 10(-5)
      Bq m (-2) S (-1) in a forest floor with the method. The specific activities of
      14C in environmental materials such as some biological and air samples were also
      determined in the vicinity of the place, where the flux measurement was made, to
      discuss the behavior of 14C in the forest ecosystem. The results indicated that
      fresh pine needles had a similar 14C specific activity to the atmospheric CO2 at
      the same height due to its fairly rapid equilibrium, 14C specific activity in the
      atmospheric CO2 has a concentration gradient near the ground surface and, at
      least in this site, CO2 with high 14C specific activity was generated by
      decomposition of soil organic matter which may be accumulated in soil as a result
      of former nuclear weapons tests.

PMID- 12054040
TI  - Seasonal variations of 222Rn concentrations in the air of a tunnel located in
      Nagano city.
AB  - The seasonal variation of 222Rn concentrations in the air of tunnels constructed
      during World War II at Nagano City has been investigated. The determination of
      222Rn concentrations in tunnel air was performed using a solid-state nuclear
      track detector technique. The monthly radon concentrations changed smoothly,
      decreasing towards winter and increasing towards summer, and it was found that
      the concentrations strongly correlate with the temperature difference between the
      inside and the outside of the tunnel. In the innermost areas of the tunnel, the
      maximum concentration was observed in July, its value being about 6500 Bq m (-3).
      The concentrations of radon in the tunnel air decrease exponentially towards the
      openings of the tunnel, which indicates that the radon concentration in the
      tunnel is basically governed by diffusion and mixing of radon gas with air. These
      observations lead to the conclusion that the seasonal variation of the radon
      concentration in the tunnel air is mainly caused by a convection current due to a
      stack effect induced by the temperature difference between the tunnel air and the
      outside air.

PMID- 12054042
TI  - Absorbed dose delivered by alpha particles calculated in cylindrical geometry.
AB  - The present work aims to develop a semi-analytical method to calculate the
      absorbed dose delivered by alpha particles in a cylindrical geometry. This method
      will be employed to reproduce the dose conversion coefficients or absorbed
      fraction of alpha particles in sensitive cells of the tracheobronchial tree
      obtained by NRC and ICRP, respectively. The difference caused by using water
      stopping power and tissue stopping power will also be investigated. Linear
      stopping powers for alpha particles in tissue and air were calculated, and the
      dependences of stopping powers on the traveled distance were established. A
      geometry model is set up for our calculations, and two different cases have been
      considered, namely the near-wall and far-wall cases. The total energy imparted to
      a unit-diameter sphere around a point is shown to be obtainable from a triple
      integral, which can be solved numerically. The absorbed dose is found to be
      independent of the diameter of the sphere being considered and additional
      assumptions about its diameter were not needed. The results obtained are in good
      agreement with those obtained previously by NRC and ICRP66. Using the semi
      analytical method developed in the present work, the dose conversion coefficients
      or absorbed fraction previously obtained by NRC and ICRP, respectively, have been
      satisfactorily reproduced. Using the tissue stopping power instead of the water
      stopping power can slightly lower the values for dose conversion coefficients in
      the bronchial region.

PMID- 12054043
TI  - Thermal neutron fluence from ultra low-level gamma-ray spectrometry of spoons
      activated during the JCO criticality accident at Tokai-mura in 1999.
AB  - During the JCO-accident in Tokai-mura in 1999, the surrounding village was
      irradiated by an uncontrolled neutron flux. At some locations in that village,
      the thermal neutron flux was determined retrospectively by measurement of the
      very low activity of 51Cr and 60Co in stainless-steel spoons using gamma-ray
      spectrometry in underground laboratories. Activities determined in the HADES
      underground facility are presented here, together with calibrations performed
      using a well-defined thermal neutron flux to directly estimate the fluence of
      thermal neutrons independent of most assumptions. The results show measurable
      51Cr in three samples and 60Co in four samples taken from locations at distances
      of up to 430m from the accident location despite the elapse of 4 half-lives of
      51Cr before measurement. Effects of air transport of the samples were considered
      and shown to be negligible.

PMID- 12054041
TI  - Variability in background levels of surface soil radionuclides in the vicinity of
      the US DOE waste isolation pilot plant.
AB  - Concentrations of radionuclides were measured in soils from a grid of locations
      surrounding the US Department of Energy Waste Isolation Pilot Plant (WIPP) in
      southeastern New Mexico and from a grid on a reference site approximately 20 km
      southeast of the WIPP site. Each of the two grids has 16 sampling locations (grid
      nodes) systematically distributed within an area of 16.580 ha. Sampling was
      conducted prior to the arrival of the first waste shipment at WIPP. Thus, the
      137Cs and 23,240Pu in the soil are expected to have been deposited as global
      fallout, although the Gnome Site, 8.8 km southwest of the WIPP, is also a
      potential source of 239,240Pu and fission products. The reference grid has
      significantly higher concentrations of fallout and natural radionuclides than the
      WIPP grid. Up to 80% of the total variability in radionuclide concentrations
      across the two grids is attributable to differences between grid nodes.
      Differences between replicates within a location account for 44-50% of the
      variability in concentrations of the uranium isotopes, but only 11-17% of the
      variability in the concentrations of the other radionuclides. Samples having
      similar abundance of radionuclides were spatially aggregated across the terrain.
      The activity concentrations of the radionuclides were strongly correlated with
      the concentrations of Al and Pb, and with the percentages of sand, silt and clay
      in the soil. Normalizing radionuclide concentrations to the concentration of Al
      or percent fine particles can help adjust for differences in soil textures among
      samples and facilitate the detection of gradients or temporal changes in soil
      concentrations.

PMID- 12054044
TI  - A general approach to transform a lake model for one radionuclide (radiocesium)
      to another (radiostrontium) and critical model tests using data for four Ural
      lakes contaminated by the fallout from the Kyshtym accident in 1957.
AB  - This paper presents results of a model test carried out within the framework of
      the COMETES project (EU). The aim of the work was to change the structure of the
      MOIRA lake model for radiocesium so that it can be applied more generally for, in
      principle, all types of radionuclides and heavy metals. This general lake model
      is used within the MOIRA decision support system (DSS; MOIRA and COMETES are
      acronyms for EU-projects). The model is based on a set of differential equations
      and a specific modelling structure. It incorporates all important fluxes to, from
      and within lakes in a general manner. Yet the model is driven by a minimum of
      variables accessible from standard maps and monitoring programs. The model can be
      separated into two parts, a general part with equations applicable for all types
      of water pollutants and a substance-specific part. This model has previously been
      validated for 137Cs from many lakes covering a wide domain and yielded excellent
      predictive power. The alterations discussed in this work are meant to be general
      and radiostrontium is used as a typical element. Radiostrontium is known to be
      more mobile than radiocesium and all abiotic parts of the model handling fixation
      and mobility have been altered. The new model for 90Sr has been critically tested
      using data from four lakes heavily contaminated with 90Sr from the Kyshtym
      accident in the Southern Urals, Russia, using empirical data from a period from
      1958 to 1995 for 90Sr in fish (here goldfish), water and sediments.

PMID- 12054045
TI  - Foliar and root uptake of 134Cs, 85Sr and 65Zn in processing tomato plants
      (Lycopersicon esculentum Mill.).
AB  - The results of an experimental study on the behaviour of 134Cs, 85Sr and 65Zn in
      processing tomato plants grown in peat substrate are presented. Plants were
      contaminated by wet deposition of 134Cs, 85Sr and 65Zn, either by sprinkling the
      above ground part at two phenological stages or by administering 134Cs, 85Sr and
      65Zn to the soil. The plants contaminated at the second phenological stage
      intercepted 38.3% less than those contaminated at the first stage, although leaf
      area increased by more than double. Transfer coefficients from peat soil to ripe
      fruit for 134Cs are significantly higher than those for 85Sr and 65Zn. Leaf to
      fruit transfer coefficients for 134Cs are one order of magnitude higher than for
      65Zn and two orders higher than for 85Sr. Only when deposition affects fruits, as
      at the second phenological stage, are transfer coefficients to fruits similar for
      the three radionuclides.

PMID- 12054046
TI  - Radiocesium in North San Francisco Bay and Baja California coastal surface
      waters.
AB  - Radiocesium, 137Cs, and rare earth elements (REEs) were determined in suspended
      material and dissolved fractions of waters across the salinity gradient in North
      San Francisco Bay (estuary). We describe the variation of this conservative
      isotope tracer with salinity and sediment load. REE data are used to
      differentiate marine and terrigenous source terrains for suspended material and
      dissolved fractions. We estimate that about 1-4 x 10(10) Bq of 137Cs migrates
      annually on suspended material through the North Bay. In addition, 137Cs
      concentrations were measured in surface waters off Baja California. Combined in
      situ water density (sigma(t)) and 137Cs data distinguish between California
      Current and Gulf of California water, and delineate areas of upwelling, where
      nutrient-rich, deep Pacific Intermediate water, with little or no 137Cs, is
      brought to the surface off promontories along Baja California.

PMID- 12054047
TI  - Isolation of a Cryptococcus neoformans serotype A MATa strain from the Italian
      environment.
AB  - Cryptococcus neoformans is a heterothallic basidiomycete which possesses a
      bipolar mating system based on two mating type alleles, MATa and MATalpha. In the
      type variety, C. neoformans var. neoformans, both mating types have been found
      among strains of one serotype, serotype D, whereas only MATalpha was identified
      after extensive survey of serotype A strains. Serotype A MA Ta appeared to be
      extinct or to exist only in a vestigial, non-functional form. We report the
      isolation of a C. n. var. neoformans serotype A MATa strain from the Italian
      environment. The strain was serotyped by slide agglutination test, genotyped by
      polymerase chain reaction (PCR) fingerprinting using the (GACA)4 primer, and its
      haploid state was determined by flow cytometry. The mating type was identified by
      PCR amplification of the pheromone a gene. In addition, the amplification of the
      four STE20 alleles, specific for the mating type of serotypes A and D, showed
      that the strain contains only the MATa locus. By crossing experiments the strain
      was found to be fertile. The interest in the finding of this fertile isolate is
      related to the possibility to construct a congenic pair of serotype A
      MATa/MATalpha strains to be used in genetic and pathogenesis studies.

PMID- 12054048
TI  - The Candida albicans cell wall-associated glyceraldehyde-3-phosphate
      dehydrogenase activity increases in response to starvation and temperature
      upshift.
AB  - We have determined the effect of environmental factors (mild thermal upshift and
      starvation) on the Candida albicans cell wall-associated glyceraldehyde-3
      phosphate dehydrogenase (cwGAPDH) activity. Temperature upshift (from 28 to 37
      degrees C) and/ or starvation (at 28 or 37 degrees C in water) of exponentially
      growing yeast cells caused an increase in cwGAPDH activity (3 to 5-, and 7 to 8
      fold, respectively). This increase in activity did not correlate with an increase
      in the amount of cwGAPDH protein present, as determined by flow cytometry,
      immunoelectron microscopy and Western-blotting. These results indicate that
      thermal upshift and starvation cause an activation of the cwGAPDH in C. albicans
      cells.

PMID- 12054049
TI  - Immuno-crossreactivity of an anti-Pichia anomala killer toxin monoclonal antibody
      with a Williopsis saturnus var. mrakii killer toxin.
AB  - A monoclonal antibody (mAbKT4), produced against the Pichia anomala ATCC 96603
      killer toxin (PaKT) was used to detect the toxin (WmKT) produced by Williopsis
      saturnus var. mrakii MUCL 41968 which inhibits the growth of a PaKT-sensitive P.
      anomala strain MUCL 41969. Immunofluorescence studies revealed that mAbKT4
      specifically labels the surface of P. anomala and W. saturnus var. mrakii,
      suggesting that both taxa secrete a killer toxin bearing a common epitope.
      Immunoblot analyses of concentrated supernatants from P. anomala and W. saturnus
      var. mrakii cultures showed that in both taxa mAbKT4 reacts with high molecular
      weight secreted proteins ranging 85-200 kDa. However, immunoblot experiments
      showed that the molecular weights of PaKT and WmKT are quite different,
      indicating that the two toxins are related but not identical molecules.

PMID- 12054050
TI  - Mechanism of antifungal action of kanosamine.
AB  - The antibiotic kanosamine inhibited growth of Saccharomyces cerevisiae and a
      range of human pathogenic fungi, including Candida albicans. Kanosamine was
      transported into C. albicans cells by the glucose transport system and
      subsequently phosphorylated. The product of its intracellular metabolism,
      kanosamine-6-phosphate, was an inhibitor of the enzyme glucosamine-6-phosphate
      synthase. Inhibition was competitive in respect to one of the substrates, D
      fructose-6-phosphate, with Ki = 5.9 mM, and was non-competitive in respect to the
      second substrate, L-glutamine. On the other hand, kanosamine-6-phosphate had no
      effect on the enzyme catalysing the next metabolic step, namely glucosamine-6
      phosphate N-acetylase. The action of kanosamine on C. albicans cells resulted in
      profound morphological changes, inhibition of septum formation and cell
      agglutination. Experiments with S. cerevisiae mutants showed that the presence of
      the Cdr1p drug efflux pump did not affect the antifungal activity of kanosamine.

PMID- 12054051
TI  - Prospective use of RFLP analysis on amplified Cryptococcus neoformans URA5 gene
      sequences for rapid identification of varieties and serotypes in clinical
      samples.
AB  - Clinical isolates of Cryptococcus neoformans, whole blood, cerebrospinal fluid,
      bronchoalveolar lavage fluid from patients with positive cryptococcal antigen
      latex-agglutination test, and spiked clinical material from healthy individuals,
      were tested by polymerase chain reaction (PCR) with primers amplifying C.
      neoformans URA5 gene sequences. To test compatibility of different DNA extraction
      protocols with the PCR-restriction fragment length polymorphism (RFLP) assay, a
      commercial DNA extraction kit (XTRAX; Gull Laboratories, UT, USA) was used
      alongside with the hexadecyltrimethylammonium bromide (CTAB) method on spiked
      biological fluids. Both methods extracted DNA from spiked clinical samples
      containing C. neoformans (8 +/- 2 cells ml(-1)) and generated amplification
      products suitable for restriction enzyme analysis. Alu I digestion differentiated
      the two varieties of C. neoformans. Three distinct RFLP patterns were obtained
      upon restriction with MspI corresponding to serotypes A, AD and B, C and D. URA5
      PCR followed by RFLP analysis, coupled with a sensitive in-house or commercially
      available DNA extraction method from clinical samples, could be successfully
      incorporated into rapid routine diagnostic strategies. It could also provide an
      expeditious tool for epidemiology-based population genetics studies.

PMID- 12054052
TI  - First report of Cryptococcus neoformans var. gattii serotype B from Greece.
AB  - A plethora of cases of Cryptococcus neoformans infections have been recorded
      worldwide in immunocompromised individuals. The number of such cases showed a
      steady rise before 1981 and increased dramatically thereafter due to the AIDS
      epidemic. A similar pattern has been seen in Greece but, so far, infections
      appear to have been caused by C. neoformans var. neoformans. This paper describes
      for the first time two culture-proven C. n. var. gattii serotype B infections in
      Greece, one in an AIDS patient and one in a patient with systemic lupus
      erythematosus.

PMID- 12054053
TI  - Levels of specific antigen (gp43), specific antibodies, and antigen-antibody
      complexes in saliva and serum of paracoccidioidomycosis patients.
AB  - The present study analyses human immunoglobulin G (IgG) antibodies directed
      against the Paracoccidioides brasiliensis exoantigen, gp43, as well as the
      presence of gp43-IgG immune complexes (ICs) in 31 samples of saliva and serum
      from 19 patients with paracoccidioidomycosis (PCM) and 12 normal donors.
      Additional analysis of secretory IgA (sIgA) was performed on the same saliva
      samples. Consistent with previous findings, a significant increased specific IgG
      level was observed in PCM patients' saliva and serum (P < 0.05). The analysis of
      serum gp43 and gp43-IgG IC demonstrated a higher level in patients with PCM (P <
      0.05); however, this difference was not statistically significant with regard to
      gp43 and gp43-IgG in saliva when compared to the healthy donors. A high level of
      sIgA in saliva of PCM patients compared to that of normal donors was also
      observed (P < 0.05). Patients exhibiting low levels of serum IgG but with high
      titres of IC were observed, thus strengthening the idea of the necessity to use
      more than one marker for diagnosis and treatment monitoring of PCM. This is the
      first report of sIgA in PCM patients' saliva and may be indicative of a
      protective role in neutralizing antigens on mucosal surfaces.

PMID- 12054054
TI  - Isolation and partial characterization of an adhesin from Fonsecaea pedrosoi.
AB  - We showed previously that mannose and N-acetylglucosamine (GlcNAc) residues are
      involved in the process of adhesion of Fonsecaea pedrosoi, the causative agent of
      chromoblastomycosis, to epithelial cells. It was then suggested that lectin-like
      molecules would be involved in the interaction. In the present study, we used
      fluorescein isothiocyanate-labeled neoglycoproteins (bovine serum albumin [BSA]
      mannose and BSA-GlcNAc) to analyze the presence of sugar-binding proteins on the
      surface of conidia of F. pedrosoi grown at 28 and 37 degrees C. Binding of the
      neoglycoproteins was measured using flow cytometry. Fungal conidia expressed high
      levels of binding sites for BSA-mannose and BSA-GlcNAc when grown at 37 degrees C
      rather than 28 degrees C. Binding was inhibited by previous incubation of the
      conidia in the presence of chloroquine and trypsin. Chloroquine treatment also
      inhibited the interaction of fungal conidia with Chinese hamster ovary cells.
      Extracts from the conidia, obtained using a mechanical cell homogenizer, were
      purified by affinity chromatography using mannose-agarose or GlcNAc-agarose
      column. Polyacrylamide gel electrophoresis of the purified material from both
      columns showed a single protein band of 50 kDa, suggesting that the same lectin
      like protein recognizes both carbohydrates.

PMID- 12054055
TI  - Analysis of restriction profiles of mitochondrial DNA from Sporothrix schenckii.
AB  - Mitochondrial DNA (mtDNA) diversity was analyzed in 42 clinical isolates of
      Sporothrix schenckii from Mexico (n = 29), Guatemala (n = 4) and Colombia (n =
      9). Based on HaeIII restriction digestion profiles, the isolates were classified
      into eight types. In addition to 24 mtDNA types previously reported in another
      study, 6 new types were found in this study. Most of the strains belong to type
      14 and type 30, the former restricted to Mexico, whereas the latter was
      distributed in Mexico, Guatemala and Colombia. The new types (25-30) were
      identified in Mexico, Guatemala and Colombia. Restriction-fragment length
      polymorphism in mtDNA of S. schenckii revealed high levels of genetic variation
      attributable to differences in restriction sites as well as in mtDNA size. Based
      on genetic distances S. schenckii types were clustered into two main groups.

PMID- 12054056
TI  - Molecular cloning, characterization and expression of the heat shock protein 60
      gene from the human pathogenic fungus Paracoccidioides brasiliensis.
AB  - A gene encoding the heat shock protein (HSP) 60 from Paracoccidioides
      brasiliensis (Pb) was cloned and characterized. The hsp60 gene is composed of
      three exons divided by two introns. Structural analysis of the promoter detected
      canonical sequences characteristic of regulatory regions from eukaryotic genes.
      The deduced amino acid sequence of the Pb hsp60 gene and the respective cloned
      cDNA consists of 592 residues highly homologous to other fungal HSP60 proteins.
      The hsp60 gene is present as a single copy in the genome, as shown by Southern
      blot analysis. The HSP60 protein was isolated from Pb yeast cellular extracts. N
      terminal amino acid sequencing of HSP60 confirmed that the cloned hsp60 gene
      correlated to the predicted protein in Pb. HSP60 expression appeared to be
      regulated during form transition in Pb, as different levels of expression were
      detected in in vitro labeling of cells and northern blot analysis. The complete
      coding region of Pb hsp60 was fused with plasmid pGEX-4T-3 and expressed in
      Escherichia coli as a glutathione S-transferase-tagged recombinant protein. The
      protein reacted with a mouse monoclonal antibody raised to a human recombinant
      HSP60. Western immunoblot experiments demonstrated that the recombinant protein
      and the native HSP60 were recognized by sera from humans with
      paracoccidioidomycosis (PCM).

PMID- 12054057
TI  - Expression of alpha tubulin during the dimorphic transition of Paracoccidioides
      brasiliensis.
AB  - In this study we analyzed the expression of (alpha-tubulin during the dimorphic
      transition of the human-pathogenic fungus Paracoccidioides brasiliensis. The
      alpha-tubulin from P. brasiliensis was recognized by a commercially available
      anti-tubulin antibody and was developmentally regulated during the dimorphic form
      transition. We detected at least two alpha-tubulin isoforms in the mycelial state
      and only one isoform in the yeast forms. This finding suggests specific roles for
      the alpha-tubulin isoforms in P. brasiliensis's yeast and mycelial forms.

PMID- 12054058
TI  - Production of extracellular enzymes by Microsporum canis and their role in its
      virulence.
AB  - Microsporum canis is the most prevalent dermatophyte of domestic animals. Several
      enzymes produced by dermatophytes, particularly keratinases, are considered to
      play a role in the virulence of this fungus. To investigate the possible
      relationship between the clinical status of M. canis infection and enzymatic
      activity of isolates, we studied the relationship between keratinase, elastase,
      lipase and DNase levels produced in vitro by different isolates and virulence as
      expressed in a guinea pig model. Samples isolated from symptomatic dogs and cats
      showed a statistically significantly (P < 0.05) higher keratinase activity than
      samples isolated from asymptomatic animals. Experimental infection of guinea pigs
      showed that a strain with high in vitro keratinase activity induced acute
      infection, which resolved clinically and mycologically faster than the infection
      induced by a strain with low keratinase activity. This suggested a strong
      correlation between high keratinase activity and the development of symptoms. The
      same correlation was not observed for other enzymes tested.

PMID- 12054059
TI  - Dopamine D3 and D4 receptor antagonists in the treatment of schizophrenia.
AB  - The findings that dopamine D3 and D4 receptors are highly expressed in limbic and
      cortical areas (D4 more than D3), and the fact that the atypical drug clozapine
      has preferential affinity for the D4 receptors have suggested an involvement of
      these receptors in schizophrenia. Subsequently, many pharmaceutical companies
      have pursued the approach of developing selective dopamine D3 or D4 antagonists
      as potential antipsychotics. This review will discuss the current status of
      selective dopamine D3 and D4 receptor antagonists for the treatment of
      schizophrenia.

PMID- 12054060
TI  - 5-HT2A antagonists in psychiatric disorders.
AB  - Several lines of evidence support a role for serotoninergic (5-HT) system
      abnormalities in the pathogenesis and treatment of several psychiatric disorders.
      This review summarizes information about the association between the 5-HT2A
      receptor gene and its relevance to schizophrenia, tardive dyskinesia, major
      depression, suicidality, anorexia nervosa and obsessive-compulsive disorder.
      Evidence is presented that implies that selective 5-HT2A antagonists may be
      considered useful in investigating the role of 5-HT2A receptor function and in
      the treatment of psychosis, and possibly alcohol and cocaine dependence.
      Additionally, findings are reviewed on the importance of 5-HT2A receptor
      antagonism in contributing to the therapeutic effect of several clinically
      effective and potential atypical antipsychotics as well as several
      antidepressants. In conclusion, the ability of selective 5-HT2A receptor
      antagonists to interfere with the heightened state of dopamine activity without
      altering basal tone, suggests that these drugs possess antipsychotic activity and
      may provide the basis for new therapies for psychosis and drug dependence, in
      addition to contributing towards a more complete understanding of 5-HT2A receptor
      function.

PMID- 12054061
TI  - Aripiprazole (Otsuka Pharmaceutical Co).
AB  - Otsuka Pharmaceuticals in collaboration with Bristol-Myers Squibb is developing
      aripiprazole, a dual dopamine autoreceptor agonist and postsynaptic D2 receptor
      antagonist, for the potential treatment of psychoses including schizophrenia
      [281327], [340364]. A regulatory filing for schizophrenia in the US was submitted
      at the end of 2001 [340364]. The compound entered phase III trials in Japan in
      1995 [192966]. Although presynaptic dopamine autoreceptor agonists may be
      efficacious in the treatment of schizophrenia, they may also potentially increase
      the risk for exacerbation of psychosis through stimulation of postsynaptic
      dopaminergic receptors [245791], [350478], [350479]. However, earlier
      neuropharmacology studies have shown that aripiprazole can act as a presynaptic
      D2 agonist while displaying an antagonistic effect at the postsynaptic D2
      receptors [281327], [337126], [350479], [424587], [424588]. In animal models,
      aripiprazole inhibits the apomorphine-induced stereotypy, without causing
      catalepsy [281327], [337126]. Moreover, in contrast to classical antipsychotics
      that produce disabling movement disorders, aripiprazole does not cause an
      upregulation of D2 receptors or an increase in expression of the c-fos mRNA in
      the striatum, in agreement with the low risk for extrapyramidal side effects
      (EPS) during aripiprazole treatment [245781], [262096], [350481], [350483].
      Collectively, aripiprazole is an important atypical antipsychotic candidate with
      a favorable safety profile. Moreover, the mechanism of action of aripiprazole
      differentiates it from both typical and atypical antipsychotics and hence, may
      provide important leads for pharmacotherapy of schizophrenia and other psychotic
      disorders. In January 2000, Lehman Brothers predicted peak sales of aripiprazole
      could reach US $500 million [357788]. In February 2001, Credit Suisse First
      Boston predicted sales of US $403 million in 2005 [399484].

PMID- 12054062
TI  - Perospirone (Sumitomo Pharmaceuticals).
AB  - Perospirone is a serotonin 5-HT2 antagonist and dopamine D2 antagonist developed
      by Sumitomo Pharmaceuticals for the potential treatment of schizophrenia and
      other psychoses [381769]. Its receptor binding profile and animal pharmacology
      resemble those of other atypical antipsychotic agents, in particular risperidone.
      In November 2000, CPAC's First Committee on Drugs recommended the approval of
      this product in Japan, [394007]; approval was granted in December 2000 [396121].
      In January 2001, the NHI price was agreed by the Chuikyo [398222] and the drug
      was added to the NHI price list in February 2001 13982261. It was finally
      launched in Japan on February 8 2001 [399401]. In November 2000, Sumitomo and
      Welfide signed an agreement whereby Welfide's subsidiary Yoshitomi Yakuhin will
      copromote perospirone [394007]. Based on data from the Chuikyo, peak sales of
      perospirone are forecast to be yen9 billion in the sixth year following launch
      [398222], [398226]. In February 2001, Sumitomo predicted that perospirone would
      reach sales of yen10 billion within five to six years [399401].

PMID- 12054063
TI  - Overview: immunotherapy for cancer--is it time for the kitchen sink?

PMID- 12054064
TI  - Epitope identification and vaccine design for cancer immunotherapy.
AB  - The development of processes for engineering multi-epitope vaccines based on the
      identification and selection of epitope packages, along with vaccine design
      optimization using epitope placements and spacers to optimize processing
      efficacy, are reviewed. The Epimmune Inc epitope identification process has been
      applied to numerous cancer types, but also applies to infectious diseases.
      Epitope-analog efforts in novel vaccine design have also been explored and their
      uses in prophylactic and therapeutic applications are eagerly anticipated.

PMID- 12054065
TI  - Cancer vaccines, a critical review--Part I.
AB  - Cancer vaccines are more properly referred to as 'active specific immunotherapy',
      and are used to treat cancers rather than to prevent them, at least at present.
      Vaccines augment already established tumor immunity, are far more specific
      against the tumor than cytokines, have little or no toxicity, and thus may easily
      be combined with other types of immunotherapy. They also elicit immunological
      memory, which may check recurrence of the tumor. Melanoma vaccines have received
      the most attention thus far. Among the several vaccines in clinical trials are
      whole cell lysates, such as Melacine, hapten-treated autologous melanoma cells (M
      Vax) and irradiated allogeneic cells (CancerVax). Regressions of metastatic
      nodules have been noted with each preparation. Controlled trials of Melacine
      indicate prolongation of survival in patients with resected stage IIB disease,
      particularly those with one or more of the following HLA class I alleles: HLA-A2
      or -A28 (-A6802), HLA-B12, -44 or -45, and HLA-C3. A combination of interferon
      alpha2b and Melacine appears to enhance the anti-tumor response in advanced
      (stage IV) disease, and is being tested in a large randomized controlled trial in
      resected stage III disease. An irradiated autologous colon carcinoma vaccine has
      improved relapse-free survival in resected stage II disease (Dukes B) in a
      controlled trial. Second-generation whole cell vaccines include those
      incorporating genes such as GM-CSF or CD80 (B7-1) to improve immunogenicity, and
      the use of immunogenic cell membranes such as large multivalent immunogen (LMI).
      Upregulation of HLA class II molecules and concomitant inhibition of the Ii
      molecule are also being explored as a strategyfor improved presentation of tumor
      associated antigens in vaccines. Complex whole cell-derived vaccines have given
      clinically superior responses compared to vaccines containing well-defined
      antigens, such as peptides or gangliosides; however, well-defined vaccines are
      theoretically more desirable because of their reproducibility.

PMID- 12054066
TI  - Cancer vaccines, a critical review--Part II.
AB  - Cancer vaccines have been explored clinically against melanomas, adenocarcinomas
      and lymphomas. Breast cancer vaccines include Theratope, MUC1 mucin peptides and
      HER-2/neu peptide vaccines. Phase II trials suggest prolongation of survival of
      advanced breast cancer patients who generate high titers of antibody to
      Theratope. In contrast, melanoma ganglioside vaccines, which also elicit only
      antibodies, have not been effective in improving survival in controlled trials.
      Anti-idiotype vaccines for solid tumors, which depend upon mimicry of the tumor
      associated antigens, have also had limited success. In lymphomas, where the
      idiotypes are the tumor-associated antigens, greater success has been achieved. A
      number of tumor-associated antigens have been identified in melanoma, such as the
      lineage related cancer-testis group (MAGE) and tyrosinase-related antigens. Non
      lineage related antigens shared among a variety of very different tumors have
      recently been demonstrated too, which may permit immunization against more than
      one tumor group. Telomerase and MG50, one of several interleukin-1 receptor
      antagonist molecules, are both immunogenic and widespread in their
      representation. Carcinoembryonic antigen is the basis for vaccines against many
      adenocarcinomas. Both viral and non-viral vectors are being used to improve the
      reactivity to peptides in adenocarcinomas. Dendritic cell-carried vaccines, which
      package the antigens ex vivo rather than depending upon in vivo uptake, are being
      extensively explored in clinical models to improve the effectiveness of defined
      vaccines, such as peptides and RNA. 'Naked' DNA vaccines injected intramuscularly
      also have their advocates. Among the most recent attempts to improve the
      immunogenicity of vaccines is the use of antigens newly identified by genomic
      techniques and 'superagonist' peptide mimics, selected from combinatorial peptide
      libraries. These modern biochemical and molecular biological methods may greatly
      expand our ability to immunize against tumor antigens, which are essentially
      'self' molecules. Finally, a greater understanding of ways in which tumors escape
      immunological detection or thwart immunological responses should lead to improved
      strategies against the tumor to augment the effect of vaccination.

PMID- 12054067
TI  - GMK (Progenics Pharmaceuticals).
AB  - Progenics Pharmaceuticals is developing GMK vaccine (a ganglioside conjugate
      vaccine coupled to keyhole limpet hemocyanin and formulated with the adjuvant QS
      21), licensed from the Memorial Sloan-Kettering Cancer Center, for the potential
      treatment of melanoma and other cancers [194258], [325284]. It was previously
      under co-development with Bristol-Myers Squibb, but in May 2001, all rights to
      the GMK vaccine were returned to Progenics [409168]. It was the first of a new
      class of ganglioside conjugate vaccine evaluated by Progenics [194258]. GMK
      vaccination induces antibodies against GM2 ganglioside capable of specifically
      killing melanoma cells. Melanoma patients with antibodies against GM2 ganglioside
      have significantly improved disease-free and overall survival compared to
      antibody-negative subjects. The vaccine is undergoing two phase III trials, the
      first comparing GMK to high-dose IFNalpha in melanoma patients with more serious
      disease and at a high risk of relapse, and the second, in collaboration with the
      European Organization for Research and Treatment of Cancer, comparing GMK (14
      doses of GMK over three years) to no treatment other than close monitoring of
      malignant melanoma patients at immediate risk of relapse [409168]. In February
      1999, Lehman Brothers predicted that the vaccine had a 50% probability of
      reaching market, with an estimated first launch date in 2002. The analysts
      predicted potential peak sales in 2008 of $150 million in the US and $100 million
      in the rest of the world at that time [319225]. In January 2000, Lehman Brothers
      expected that an NDA filing would take place in 2002, with possible launch of the
      vaccine in 2003. In addition, Lehman Brothers estimated potential peak sales at
      $500 million [357788]. In August 2000, Punk, Ziegel & Company predicted that
      Progenics Pharmaceuticals will become sustainably profitable in 2003 following
      the launch of GMK and PRO-542 in 2002 [390063]. In July 2001, Ladenburg Thalmann
      predicted a $257 million market potential for GMK in the US, with the non-US
      market equivalent to the US market. A launch date of 2005 in the US, with a
      worldwide launch in 2006, was estimated [433347].

PMID- 12054068
TI  - Bexxar (Corixa/GlaxoSmithKline).
AB  - Bexxar (131I tositumomab) is a radiolabeled anti-CD20 monoclonal antibody for the
      treatment of relapsed and refractory follicular/low-grade and transformed non
      Hodgkin's lymphoma. It has shown high response rates with durable complete
      remissions in patients who have received either prior chemotherapy or rituximab
      (Rituxan, MabThera; IDEC Pharmaceuticals Corp/Genentech/F Hoffmann La Roche).
      Complications include myelosuppression, secondary acute leukemia, myelodysplasia
      and hypothyroidism. The role of this promising new agent is being defined in
      phase II and III trials. In February 2001, ABN Amro Predicted launch in 2001 and
      sales of US $25 million rising to US $70 million in 2003 [422363]. Corixa and
      GlaxoSmithKline anticipate a launch in the US in 2002 [424619].

PMID- 12054069
TI  - Memory T-cells in non-lymphoid tissues.
AB  - Recent studies have shown that long-lived memory CD8 T-cell populations can be
      subdivided into two distinct groups. The central pool of resting memory cells in
      lymph organs has been extensively analyzed. However, a second subset of partially
      activated CD8 memory T-cells has recently been identified in non-lymphoid
      tissues. In respiratory virus models, a strong correlation between the numbers of
      antigen-specific T-cells in lung tissues and effective protective cellular
      immunity suggests that boosting the numbers of memory T-cells in non-lymphoid
      tissues may be a fruitful approach in vaccine development for viral infections.

PMID- 12054070
TI  - Update on human papillomavirus vaccines for cervical cancer.
AB  - Cervical cancer is a leading cause of cancer related mortality in women,
      particularly in developing countries. As a result of several recent advances in
      molecular biology, the causal association between human papillomavirus (HPV)
      infection and cervical cancer has been firmly established and the oncogenic
      potential of certain HPV types has been clearly demonstrated. In recognition of
      the causal association of cervical cancer with a sexually transmitted viral
      infection, substantial interest has arisen to develop effective prophylactic and
      therapeutic vaccines. Prophylactic strategies currently under investigation focus
      on the induction of effective humoral immune responses that are potentially
      protective against subsequent HPV infection. Using recombinant techniques to
      express the L1 major capsid protein, papillomavirus-like particles (VLPs) have
      been synthesized in order to induce neutralizing antibody responses and
      impressive immunoprophylactic effects have been demonstrated in both animals and
      humans. For the treatment of existing HPV infection, techniques to improve
      cellular immunity by enhancing viral antigen recognition are being studied. For
      this purpose, the oncogenic proteins E6 and E7 of HPV-16 and -18 are the focus of
      current clinical trials for cervical cancer patients. The development of
      successful HPV-specific vaccines may offer an attractive and cost-effective
      alternative to existing screening and treatment programs for cervical cancer.

PMID- 12054071
TI  - StaphVAX (Nabi).
AB  - StaphVAX is a bivalent polysaccharide- and protein-conjugated vaccine, directed
      against capsular Staphylococcus aureus types 5 and 8, which are associated with
      80 to 90% of S aureus clinical infections. The vaccine is being developed by
      Nabifor the potential treatment of infections in kidney patients who are
      receiving peritoneal dialysis and are prone to serious staphylococcal infections
      [193495], [221403], [222643], [283114]. In February 2001, Nabi revealed that it
      was movingforward during the second quarter of 2001 with previously stated plans
      to conduct a boosting study of StaphVAX in patients with end-stage renal disease
      (ESRD). This study would be conducted in patients who were enrolled in the first
      phase III trial and the company expected completion by early 2002 [283114]. The
      company was also progressing with scale-up of the manufacturing process for
      commercial production of the vaccine. Nabi met with the FDA in December 2000 to
      review results from its phase III trial of StaphVAX in patients with ESRD. The
      FDA stated that a definitive demonstration of preventative efficacy in another
      well-designed, randomized and controlled clinical study would be required for
      licensing. At this time, Nabi was making plans for this second phase III trial,
      despite plans to appeal the FDA's decision [397729].

PMID- 12054072
TI  - Meningitis C vaccine (North American vaccine).
AB  - North American Vaccine Inc (NAVI) has launched a conjugate polysaccharide
      vaccinefor the prevention of meningitis caused by group C meningococcal bacteria
      [433475]. The vaccine is based upon conjugate technology, incorporating the
      serogroup C polysaccharide (CPS) of all three major serogroups. Antibody
      dependent, complement-mediated activity was demonstrated in mice and non-human
      primates, with no detectable adverse effects [277193]. Approval was filed for in
      the UK in January 2000 [353305]. In July 2000, Baxter received approval for
      NeisVac-C in the UK, and by September 2000 the vaccine was expected to be
      incorporated into the NHS's immunization campaign against meningitis C [381225].
      NeisVac-C will initially appear labeled from NAVI; Baxter completed its
      acquisition of NAVI in June 2000 [375389]. Baxter estimates the worldwide global
      market for the vaccine at US $600 million per year [376204].

PMID- 12054073
TI  - Varivax (Merck & Co).
AB  - Varivax is a live-attenuated varicella vaccine developed and launched in the US
      by Merck & Co for the treatment of chickenpox [413319]. The vaccine uses the Oka
      strain of the varicella virus licensed from the Biken Institute at Osaka
      University in Japan [178223]. By June 2001, Merck was also developing the vaccine
      for use in adults for herpes zoster infection [413319]. The FDA required post
      marketing studies as a condition for its approval of Varivax, which was granted
      in March 1995 [174416]. The Centers for Disease Control & Prevention Advisory
      Committee on Immunization Practices recommended that Varivax should be
      administered at the same time as the measles, mumps and rubella vaccine.
      Unvaccinated children between the ages of 19 months and 13 years should be
      vaccinated by the time they are 13 years old [180148]. Varivax, from its launch
      in the spring of 1995 to the end of the third quarter 1995, produced sales of US
      $60 million [196542]. In June 2000, a second generation of Varivax, Varivax II,
      was launched for vaccination against chickenpox in individuals 12 months of age
      and older. Varivax II prevents the transmission of chickenpox with exactly the
      same safety and efficacy profile as Varivax; however, the new Varivax II has the
      advantage of being refrigerator-stable [371871].

PMID- 12054074
TI  - Overview: why are corticosteroids ineffective in COPD?

PMID- 12054075
TI  - Antibiotics as anti-inflammatory agents.
AB  - Although the empirical use of some antibacterial agents in various inflammatory
      diseases has proved beneficial in the past, it is only recently that the
      therapeutic anti-inflammatory potential of cyclines and macrolides has received
      attention worldwide. Other drugs like fosfomycin and some quinolones are also
      contenders for this role. Owing to the complexity of the inflammatory process,
      which involves many redundant cellular effectors and soluble mediators, and the
      obscure etiopathogenesis of many inflammatory diseases (some of which may be
      secondary to persistent infections), the precise mechanisms underlying the
      therapeutic benefit of anti-inflammatory antibiotics remain to be elucidated.
      Structure-activity relationships are the key to developing new anti-inflammatory
      agents derived from antibacterial drugs.

PMID- 12054076
TI  - Adenosine receptor ligands as potential therapeutics in asthma.
AB  - Increasingly persuasive evidence implicates adenosine in the pathophysiology of
      asthma. Adenosine exerts its manifold biological activities by interacting with
      at least four adenosine receptor subtypes. Selective activation or blockade of
      these sites is being exploited by the pharmaceutical industry in an attempt to
      generate novel therapies for asthma. Compounds have been designed which
      downregulate the A1 receptor, activate the A2A receptor or block the A2B receptor
      and are currently in development for this condition.

PMID- 12054077
TI  - Ciclesonide ( Byk Gulden).
AB  - Ciclesonide, a non-halogenated inhaled corticosteroid with anti-inflammatory
      activity, is under development by Byk Gulden, Aventis and Teijin as a potential
      treatment for asthma [213439]. It was also being developed by Byk Gulden for
      chronic obstructive pulmonary disease (COPD), but no development had been
      reported for this indication since 1999; however, Teijin was carrying out
      clinical trials in this indication at the end of 2000. During 2000, Byk Gulden
      was carrying out phase III trials in the US and Europe and in March 2001, results
      were expected in the third quarter of 2001 [312399], [383726], [423659]. Two
      inhalant formulations (multidose powder and propellant filled) and a nasal
      formulation of ciclesonide are being developed by Byk Gulden for the treatment of
      asthma and seasonal allergic rhinitis, respectively [337147]. The compound is
      formulated for once-daily dosing and demonstrated good efficacy without
      corticosteroid-associated systemic side effects [409257]. In January 2001, Byk
      Gulden expected launch of a CFC-free multidose inhaler formulation in 2003
      [395596]; in March 1999, launch of a nasal formulation was expected in 2004 and a
      multidose powder inhaler in 2005 [337147]. By September 2001, the compound was in
      phase III trials in the US for asthma, with a potential US launch anticipated by
      Aventis in 2004 [423465]. In November 2001, Aventis expected to submit an NDA to
      the FDA in 2003 [428057]. Teijin, which has a development and licensing agreement
      with Byk Gulden for the treatment of asthma and COPD in Japan, commenced phase I
      trials of ciclesonide in Japan in spring 1999, had completed these during 2000,
      and began phase II trials by September of that year [383726]. An NDA is expected
      to befiled in Japan in 2003. In October 2000 and April 2001, Merrill Lynch
      predicted peak sales of Euro400 million in 2007, with sales of Euro5 million in
      2002, rising to Euro150 million in 2004 [395562], [420574]. Deutsche Bank
      predicted in August 2001, that sales of the product would reach Euro70 million in
      2004, rising to Euro150 million in 2005 [420814].

PMID- 12054078
TI  - Antiarrhythmics in atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common arrhthymia that exists in both the acute and
      chronic form. As the molecular basis of arrhythmogenesis is further elucidated,
      the discovery of novel antiarrhythmic agents, which can be tailored to individual
      patients and the particular subtype of AF, while minimizing potential side
      effects, will become possible.

PMID- 12054079
TI  - Conivaptan (Yamanouchi).
AB  - Yamanouchi is developing conivaptan, an orally active vasopressin V1A and V2
      antagonist for the potential treatment of heart failure, edema and hyponatremia.
      The company anticipated launch of the product for hyponatremia in 2002 [362201].
      By May 2001, Yamanouchi was continuing phase II trials in Japan for hyponatremia
      and heart failure, and in the US and Europe for heart failure, and phase III
      trials in the US and Europe for hyponatremia [411763]. In July 2000, it had been
      reported that conivaptan was undergoing phase III trials in both the US and
      Europefor hyponatremia and heart failure [377561]. In April 1998, Warner-Lambert
      (now Pfizer) acquired the rights to YM-087 for US, South America, Europe and
      Africa, while Yamanouchi retains copromotion rights, but by November 2000, Pfizer
      had cancelled its licensing contract to market the drug in the US [397901]. In
      September 2001, analysts at Morgan Stanley predicted launch of conivaptan for
      hyponatremia in the US between 2004 and 2005 [422782]. In October 2001, analysts
      at Credit Suisse First Boston predicted that an NDA would be filed in 2002
      followed by launch in 2003, with peak annual sales of $50 million and $300
      million for hyponatremia and heart failure, respectively [427028].

PMID- 12054080
TI  - CVT-510 (CV Therapeutics).
AB  - CVT-510, the lead compound from a series of selective adenosine A1 receptor
      agonists, is being developed by CV Therapeutics for the potential treatment of
      supraventricular tachycardias and atrial arrhythmias [224364], [299365]. Phase II
      trialsfor atrial fibrillation commenced in December 1999 [349469], while a phase
      III trial for paroxysmal supraventricular tachycardia (PSVT) began in June 2001;
      this multicenter, randomized, double-blind, placebo-controlled trial, was to
      determine the safety and efficacy of CVT-510 in the conversion of PS VT to normal
      sinus rhythm [414190]. Analysts at Morgan Stanley predicted in December 2001,
      that the product would befiled with the FDA in 2004 and be launched onto the US
      market in 2005, with revenues of US $25 million, rising to US $83 million in 2006
      [435233].

PMID- 12054081
TI  - Development of WF10, a novel macrophage-regulating agent.
AB  - WF10 represents a new class of drug involved in regulating macrophage function
      both in vitro and in vivo. In the US, WF10 is being evaluated in patients with
      advanced HIV infection as an adjunct to highly active antiretroviral therapy
      (HAART). To date, most therapeutic efforts to treat HIV infection have focused on
      inhibition of viral replication with the goal of decreasing viral load. The
      introduction of HAART was associated with a dramatic decline in AIDS-related
      mortality; however, recent indications suggest that the trend maybe changing.
      WF10, which contains chlorite as the active principle, causes profound changes in
      macrophage function and activation of gene expression, and appears to
      downregulate inappropriate immunological activation. The loss of T-cell function
      observed in HIV-infected patients likely requires the involvement of chronically
      activated macrophages. Therefore, the persistently activated macrophage
      represents a therapeutic target that is, unlike HIV, not highly mutable. With
      this target as a focus, WF10 is being developed for use in advanced HIV disease.
      WF10 is currently being studied in the US, Europe and Asia for treatment of late
      stage HIV disease, as well as recurrent prostate cancer, late post-radiation
      cystitis, autoimmune disease and chronic active hepatitis C disease.

PMID- 12054082
TI  - Heterologous prime-boost vaccination strategies for HIV-1: augmenting cellular
      immune responses.
AB  - Cellular immune responses, specifically those mediated by CD8+ cytotoxic T
      lymphocytes and CD4+ helper T-lymphocytes, are needed to control HIV-1 in vivo
      and to mediate viral clearance. Vaccines capable of inducing cellular immune
      responses are, therefore, widely considered as necessary for controlling the
      spread of HIV-1. Numerous different vaccine delivery formats designed to induce
      cellular immune responses have been evaluated in animal models and clinical
      trials. These include adjuvant-supplemented peptide- or protein-based
      formulations, DNA vaccines and viral vectors. While none of the current
      generation vaccine delivery technologies have proved potent enough for stand
      alone use against HIV-1-infection, mixed delivery vaccine formats, vaccination
      schemes known as heterologous prime-boost, have proved to be significantly potent
      methods for inducing cellular immune responses. Different forms of heterologous
      prime-boost vaccines are currently being tested in numerous clinical trials and
      hold significant promise.

PMID- 12054083
TI  - Sch-351125 and Sch-350634. Schering-Plough.
AB  - Schering-Plough is developing Sch-351125 (Sch-C), the lead in a series of CCR5
      inhibitors, for the potential treatment of HIV infection. By March 2001, it had
      entered phase I studies in the US, however, by April 2001, these had been
      suspended based in part on observed QTc prolongation at the highest dose. By
      December 2001, a new phase I trial had been initiated in France. The company has
      continued to investigate a number of second-generation CCR5 receptor antagonists,
      including Sch-350634, for the potential treatment of HIV infection. Although it
      was reported at two separate meetings in early 2001 that Sch-350634 was in phase
      I/II trials, in April 2001, Schering-Plough confirmed that the compound was not
      in clinical development at that time and that a preclinical toxicology program
      was scheduled for late 2001. In December 2001, Morgan Stanley predicted a 2004
      launch for a compound arising from the CCR5 inhibitor program, with sales of
      US$100 million in 2004, US$200 million in 2005, rising to US$300 million in 2006.

PMID- 12054085
TI  - Remune. Immune Response.
AB  - The Immune Response Corp (IRC) is developing Remune, a potential HIV therapeutic
      vaccine. Remune is based on the Salk Immunogen, which is derived from an HIV
      isolate which has been inactivated by chemical depletion of glycoprotein 120
      (gp120). Preliminary data suggested that Remune, in combination with antiviral
      drug therapy, results in undetectable levels of HIV. Phase III trials commenced
      in May 1997 and it was initially expected that registration filings would be made
      in 1999. However, following interim analysis of the 2500-patient, multicenter,
      double-blind, pivotal phase III study (study 806) in May 1999, an independent
      panel recommended concluding the clinical endpoint trial and IRC and licensee,
      Agouron, decided to pursue alternative regulatory strategies, including
      initiating two additional phase III surrogate marker trials. Despite this,
      Agouron gave IRC notice of termination of its continued development in July 2001.
      In August 2001, IRC informed Agouron that, due to the total number of endpoints
      to date falling short of that previously assumed by Agouron, it did not intend to
      continue Agouron's Study 202 of Remune. In July 2001, licensee Trinity Medical
      Group filed an NDA with the governing health authorities in Thailand for Remune.
      The Thai FDA certified Immune Response's Remune manufacturing facility as being
      in compliance with GMP standards, following an on site inspection by Thai
      officials in November 2001 that was performed as a requirement of Trinity's Thai
      NDA. As a result of this certification, Trinity expected that a "timely
      determination" could be made by the Thai FDA. Rhjne-Poulenc Rorer discontinued
      its part in the development of Remune, with all manufacturing, marketing and
      distribution rights reverting to IRC. After Agouron returned rights to Remune in
      July 2001, IRC heldfull rights in the US, Europe and Japan, while collaborating
      with its partners Trinity Medical Group and Roemmers Laboratory in the Southeast
      Asian and Latin American markets, respectively. In June 1998, Merrill Lynch had
      expected an FDA filing for Remune by the end of 1999, and in May 1999 Agouron was
      hoping to file an NDA for the use of Remune against AIDS during 2001. Analysts at
      Lehman Brothers predicted in September 2001, that the product would be launched
      onto the market with sales of US$150 million in 2004.

PMID- 12054084
TI  - Fosamprenavir. Vertex Pharmaceuticals/GlaxoSmithKline.
AB  - Fosamprenavir, a Vertex Pharmaceuticals phosphate ester prodrug of the HIV
      protease inhibitor amprenavir, is under development by GlaxoSmithKline (GSK;
      formerly Glaxo Wellcome) for the potential treatment of HIV infection in adults
      and children. By November 2000, it was in phase III trials; a third phase III
      trial was initiated in April 2001. In October 2001, GSK expected filing in both
      the EU and US in 2002. In January 2002, Vertex anticipated an NDA filing during
      the second half of 2002. Fast-track status for fosamprenavir was received by
      Glaxo Wellcome in December 1999. As of January 2002, enrollment was complete for
      two of the three phase III trials, and an NDA was expected to be filed during
      2002. Fosamprenavir was first synthesized at Vertex as part of a collaboration
      with Glaxo Wellcome and by 1999, it was being developed by Glaxo Wellcome as part
      of an ongoing agreement between the two companies. In September 2000 and January
      2001, Merrill Lynch predicted a 2002 launch, with sales of pounds sterling 50
      million in 2002, rising to pounds sterling 150 million in 2004.

PMID- 12054086
TI  - Chemokines in transplant rejection.
AB  - Recent studies in transplant biology have demonstrated a role for chemokines in
      the migration of leukocytes into transplanted tissue. There is further evidence
      that modulation of the action of chemokines at their receptors can improve the
      outcome of acute rejection as well as long-term graft survival. A number of
      clinical therapies, based on both small molecules and biologicals, are currently
      under investigation with the potential for selective immunosupression. This
      article discusses the chemokines and receptors identified as the best
      characterized molecular targets, as well as the therapies under investigation for
      these targets.

PMID- 12054087
TI  - Targeting IL-15 as a therapeutic strategy in organ transplant rejection.
AB  - Much effort is currently directed towards generating and evaluating agents that
      target the individual components of the alloimmune response, with a view to
      promoting allograft survival accompanied by minimum side effects. Recently, there
      has been considerable interest in inhibiting individual cytokine/receptor
      interactions since they are key elements in pathways for differentiation of
      immune effector cells. This article examines the utility of targeting
      interactions of interleukin (IL)-15 with its receptor as a strategy for disabling
      the T-cell activation events following recognition of foreign major and minor
      histocompatibility antigens. Experimental evidence suggests that interrupting IL
      15/IL-15R interaction may be of therapeutic value in preventing allograft
      rejection.

PMID- 12054088
TI  - Nuvion. Protein Design Labs.
AB  - Protein Design Labs Inc (PDL) is developing SMART anti-CD3 (Nuvion) as a
      potential therapeutic for autoimmune diseases such as inflammatory bowel disease
      (IBD), and as a prophylactic for transplant rejection. The therapy had been in
      phase II trials for the prevention of kidney rejection, but in December 2000 PDL
      decided not to continue the development of Nuvion in kidney transplantation to
      allow the company to focus on the rapid development of Nuvion for the treatment
      of acute GvHD, as well as on the larger autoimmune indications 13921621. In April
      1999, Nuvion was in phase I/II trials for the treatment of psoriasis and phase I
      trials for GvHD, with phase II/III trials planned for 2001 for this indication.
      Following the release of disappointing trial results in June 2001, however, the
      development of Nuvion for the psoriasis indication was dropped. As of December
      2000, PDL planned to initiate a phase I trial in IBD in the near future. In March
      1999, Protein Design Labs was issued US-05834597. The patent relates generally to
      certain modifications of the constant (Fc) region of IgG2 antibodies and more
      specifically to anti-CD3 antibodies incorporating these modifications, including
      the company's SMART anti-CD3 antibody. In January 2002, analysts at Salomon Smith
      Barney predicted that the product would make sales of US $3.13 million in 2005,
      rising to US $7.20 million in 2006.

PMID- 12054089
TI  - ABCA1: regulation, function and relationship to atherosclerosis.
AB  - Since the identification of mutations in the ATP-binding cassette transporter
      (ABCA1), the relationship between ABCA1 expression, cholesterol efflux, high
      density lipoprotein (HDL) biosynthesis and cholesterol homeostasis has been a
      subject of intense investigation. Several studies have provided significant new
      information with regards to pathways controlling ABCA1 expression and activity
      and established that this transporter facilitates the efflux of cholesterol and
      phospholipids to apoprotein acceptors, leading to the formation of nascent HDL
      particles. Although ABCA1 appears to play a critical role in cholesterol flux
      from tissues, and despite a considerable interest in developing pharmacological
      agents that increase ABCA1 activity, the role of ABCA1 in preventing
      atherosclerosis remains unclear.

PMID- 12054090
TI  - Use of recombinant apolipoproteins in vascular diseases: the case of apoA-I.
AB  - Apolipoprotein (apo) A-I, because of its anti-atherogenic properties, represents
      a powerful approach to the management of vascular diseases. Infusion of apoA-I
      containing synthetic high-density lipoprotein (HDL) inhibits atherosclerosis
      progression or prevents restenosis in experimental animals, and apoA-I liposomes
      are capable of stimulating reverse cholesterol transport in humans. Moreover,
      many experimental studies have been conducted with a molecular variant of apoA-I,
      apoA-I(Milano), characterized by a prolonged residence time in plasma and
      improved function, which may offer an even better approach to the therapeutic
      handling of arterial disease.

PMID- 12054091
TI  - Ezetimibe. Schering-Plough.
AB  - Ezetimibe (Sch-58235) is a cholesterol absorption inhibitor under development by
      Schering-Plough (SP), in collaboration with Merck, for the potential treatment of
      hypercholesterolemia. In late December 2001, the companies filed an NDA in the US
      for this indication. SP is studying ezetimibe as a monotherapy for lowering lipid
      levels, and also in combination with commonly used statins therapies. The company
      believes that ezetimibe will have additive effects with the statins, inhibiting
      the absorption of cholesterol in the intestine, while the statins work by
      inhibiting the production of cholesterol in the liver. In May 2000, SP and Merck
      signed an agreementfor the codevelopment of ezetimibe covering its uses as a
      monotherapy, in combination with statins, and as a fixed combination with
      simvastatin. In December 2001, Merck and SP expanded their partnership launched
      in the US in 2000, to develop and market ezetimibe. In August and September 2001,
      Credit Suisse First Boston predicted ezetimibe sales of US $420 million in 2003
      and US $959 million in 2004. Analysts at Salomon Smith Barney predicted in
      November 2001 that the product would be launched in 2003.

PMID- 12054092
TI  - AGI-1067. AtheroGenics.
AB  - AGI-1067 is an oral VCAM-1 (vascular cell adhesion molecule-1) gene expression
      inhibitor under development by AtheroGenics for the potential prevention of
      atherosclerosis (hypercholesterolemia) and restenosis. AGI-1067 was also being
      developed in collaboration with Schering-Plough; however, in October 2001, all
      rights to the drug were returned to AtheroGenics. In February 2001, dosing was
      completed in phase II trials for the potential treatment and prevention of
      restenosis and atherosclerosis following angioplasty. In December 2001, further
      phase II trials (CART-2) were initiated for the treatment of restenosis and
      atherosclerosis. Early-phase clinical trials are ongoing for the prevention of
      atherosclerosis. In January 2002, analysts at Adams, Harkness & Hill predicted
      that AGI-1067 would be launched in the second half of 2005, with sales of US $100
      m in that year and US $540 m in 2006. It was also believed that AtheroGenics
      would look to sign a marketing partnership following the expected completion of
      the CART-2 trial in 2002.

PMID- 12054093
TI  - Cannabis: old medicine with new promise for neurological disorders.
AB  - Marijuana is a complex substance containing over 60 different forms of
      cannabinoids, the active ingredients. Cannabinoids are now known to have the
      capacity for neuromodulation, via direct, receptor-based mechanisms at numerous
      levels within the nervous system. These have therapeutic properties that may be
      applicable to the treatment of neurological disorders; including anti-oxidative,
      neuroprotective, analgesic and anti-inflammatory actions; immunomodulation,
      modulation of glial cells and tumor growth regulation. This article reviews the
      emerging research on the physiological mechanisms of endogenous and exogenous
      cannabinoids in the context of neurological disease.

PMID- 12054094
TI  - Current treatment options in neuropathic pain.
AB  - Neuropathic pain results from damage to the nervous system due to many diverse
      processes. It causes persistent, distressing pain that is reputedly unresponsive
      to conventional analgesics. Treatment is best managed in a multi-therapy pain
      clinic setting and pharmacotherapy is one facet of this treatment. There is no
      single effective drug treatment and patients have been empirically treated with
      antidepressants and antiepileptics in the past. This review focuses on evidence
      from randomized controlled trials to assess the efficacy of the currently
      available drug treatments.

PMID- 12054095
TI  - Sensitization: its role in primary headache.
AB  - The pathophysiology of the two most common primary headaches, migraine and
      tension-type headache, is complex and not yet fully understood. Recent animal and
      human studies examining these headaches indicate that the nociceptive input to
      the central nervous system (CNS) may be increased due to activation or
      sensitization of peripheral sensory afferents. The barrage of nociceptive
      impulses may result in sensitization of second- and third-order neurons in the
      CNS. In this way, sensitization may play a role in initiation and maintenance of
      migraine and tension-type headache. It is likely that the effects of established
      medication for both disorders may be partly due to a reduction in sensitization.
      Several interesting drugs that counteract sensitization are under development,
      and targeting this mode of action seems to be a promising way of improving the
      treatment for these prevalent disorders.

PMID- 12054096
TI  - Antidepressants in pain management.
AB  - Antidepressants exhibit a number of pharmacological mechanisms, including
      norepinephrine and serotonin modulation, direct and indirect effects on opioid
      receptors, inhibition of histamine, cholinergic and N-methyl-D-aspartate
      receptors, and inhibition of ion channel activity. Although it is not entirely
      clear which mechanisms produce analgesia and to what extent, the available animal
      and clinical trials data indicates that tricyclic antidepressants are effective
      in treating many types of pain. The newer selective serotonin reuptake inhibitors
      also appear to be effective for chronic headache and other non-neuropathic forms
      of chronic pain but are not as well studied. This article reviews the current
      basic and clinical research on antidepressants in pain management.

PMID- 12054097
TI  - EN-3231. Endo Pharmaceuticals.
AB  - Endo (which acquired Algos in July 2000) has developed EN-3231, a combination of
      morphine and dextromethorphan, for the treatment of moderate-to-severe chronic
      pain. In October 1998, the FDA accepted for filing the company's NDA submission
      on EN-3231, which was submitted in August 1998. However, in August 1999, Algos
      received a 'non-approvable' letter from the FDA for EN-3231. In September 2000,
      the company met with the FDA to discuss what information the FDA required in
      order to approve EN-3231. The FDA requested a second pivotal trial, which Endo
      initiated promptly. Endo hoped to file its supplement to the NDA during 2002.

PMID- 12054098
TI  - E-TRANS fentanyl. ALZA.
AB  - ALZA and Crescendo are developing E-TRANS fentanyl, an electrotransport system
      (ETS) delivery offentanyl that allows self-titration of the drug by the patient,
      for the potential management of acute pain. The product was previously being
      developed in collaboration with Janssen, but by February 2000, Janssen was no
      longer involved in its development. In January 1998, Janssen, ALZA and Crescendo
      had plans to develop the product for the potential treatment of chronic pain in
      addition to the acute pain indication; however, no further development for this
      indication has been reported since that date. ETS is able to deliver drugs that
      normally would not diffuse across the skin. A small electric current passes
      through the patient's skin, between the two electrodes on the patch. Charged drug
      molecules are attracted to the electrode of the opposite polarity to their own.
      Manipulating the charge on drug molecules is relatively easy in most instances,
      so the technology should be applicable to the majority of drugs that do not lend
      themselves to passive diffusion. ETS technology is also potentially useful in
      delivering rapid boluses of drug on demand. In February 2000, Merrill Lynch
      predicted E-TRANS fentanyl sales at US $30 million in 2002, rising to US $131
      million in 2004. Analysts at SG Cowen predicted in March 2001, that E-TRANS
      fentanyl would be rolled out during 2003 and that sales would reach US $40 to 50
      million in 2004. In April 2001, Merrill Lynch predicted earliest launch in 2003.

PMID- 12054100
TI  - Overview: the art of cancer drug screening: molecular target versus milieu-based
      screens.

PMID- 12054099
TI  - Gabapentin. Pfizer.
AB  - Gabapentin has been approved for the treatment of neuropathic pain in six
      European countries, New Zealand and Australia, and numerous countries in Latin
      America. By January 2001, Pfizer was preparing to file an NDA in the US for this
      indication; by October 2001, this NDA had been filed with the FDA. The drug is a
      GABA analog, but is not a GABA mimetic, although some neurons that respond to
      gabapentin are GABAergic. Gabapentin, at relevant concentrations, binds to an
      auxiliary protein of voltage-gated calcium channels (a2/3) and apparently, as a
      result, modulates the action of calcium channels and neurotransmitter release.
      This may account for many of its pharmacological actions. Gabapentin is also a
      substrate for the large neutral amino acid transporter, and this may be the major
      route allowing gabapentin access to the CNS. Modulation of synaptic transmission
      between primary afferents and substantia gelatinosa neurons, and blockade of
      signal transduction, are two potential mechanisms of action, in addition to
      inhibition of glutamate release by voltage-sensitive calcium channels. In
      September 2001, Morgan Stanley predicted sales of US $1871 million in 2002
      falling to US $413 million in 2006.

PMID- 12054101
TI  - Small molecules in anti-angiogenic therapy.
AB  - Angiogenesis, or the formation of new blood vessels from preexisting capillaries,
      is a sequence of events that occurs in many physiological and pathological
      conditions, including cancer. The identification of several pro-angiogenic
      factors and the recent description of endogenous inhibitors of angiogenesis, has
      made interference with vessel formation an attractive potential therapeutic
      option. Several compounds with anti-angiogenic or antivascular properties have
      been identified, and several of them have entered patient studies in cancer on
      the basis of promising preclinical results. However, this development of
      compounds that are not directly cytotoxic to cancer cells is problematic in terms
      of trial design and interpretation. This review discusses classes of molecules
      that interfere specifically with regulatory elements of the angiogenic process,
      and comments upon their stage of development and characteristics in clinical
      trials.

PMID- 12054102
TI  - Imatinib. Novartis.
AB  - Novartis has launched imatinib, an inhibitor of tyrosine kinases, including Bcr
      Abl, for the treatment of chronic myeloid leukemia (CML). Imatinib selectively
      inhibits activation of target proteins involved in cellular proliferation. It
      also inhibits c-KIT tyrosine kinase activity and is equally effective against
      both wild-type and constitutively active enzyme. Close correlation between in
      vitro responses to IFNalpha and imatinib suggested that it may be an alternative
      to IFNalpha therapy for chronic-phase CML, and the compound has the advantage
      that it can be administered orally. Futhermore, Bcr-Abl-expressing cells treated
      with imatinib undergo apoptosis. Imatinib also has potential for the treatment of
      other cancers that express these kinases, including acute lymphocytic leukemia
      and certain solid tumors. In February 2002, the FDA approved imatinib for the
      treatment of inoperable and/or metastatic malignant gastrointestinal stromal
      tumors (GIST); in September 2001, launch for the indication was expected in 2002.
      In November 2000, imatinib was granted Orphan Drug status in Japan for the target
      indication of Philadelphia chromosome-positive leukemia. By May 2001, imatinib
      had entered phase II trials for small cell lung cancer, prostate cancer and
      glioma. Imatinib has been launched in more than 35 countries, including the US,
      Brazil, Switzerland, Australia and the UK. By December 2001, the drug had also
      been launched in Japan. The drug is marketed as Gleevec (imatinib mesilate) in
      the US, and Glivec (imatinib) outside the US. In August 2001, Deutsche Bank
      estimated sales of SFr 233 million in 2001, rising to SFr 850 million in 2005;
      while Bear Stearns & Co predicted sales of SFr 250 million in 2001, rising to SFr
      800 million in 2005.

PMID- 12054103
TI  - BMS-275291. Bristol-Myers Squibb.
AB  - Bristol-Myers Squibb (BMS) is developing BMS-275291, which is a matrix
      metalloproteinase (MMP) inhibitor, for the potential treatment of cancer. It was
      originally developed by Chiroscience R&D (now known as Celltech Group plc), and
      it inhibits a broad range of MMPs known to be associated with the growth and
      spread of tumors. Advantageously, it does not inhibit MMP-mediated shedding
      events, which may be involved in the side effects associated withfirst-generation
      MMP inhibitors. ByMarch 2001, BMS-275291 was undergoing phase II/III trials, as
      an adjunct to standard chemotherapy, involving non-small cell lung cancer
      patients. In March 1999, Lehman Brothers predicted that the compound had a 25%
      chance of reaching the market, with a possible launch anticipated in 2005 and
      potential peak sales of $500 million in 2010. In November 2000, Lehman Brothers
      revised their predictions estimating a 2004 launch with a 20% chance of reaching
      the market; predicted peak sales were unchanged. In January 2002, Morgan Stanley
      Dean Witter expressed the view that release of positive phase II/III trials data
      would surprise stock markets.

PMID- 12054104
TI  - Geographical and temporal variation in levels of organochlorine contaminants in
      marine mammals.
AB  - The interpretation of the spatial and temporal patterns of variation in
      organochlorine concentrations in marine mammal populations is complex because of
      the lack of wide-scale, long-term surveys. Therefore the results from several
      surveys must be combined and this causes undesired heterogeneity due to
      differences in the sampling and analytical techniques used and in the biological
      characteristics of the individuals sampled. Moreover, information is not
      homogeneously distributed in either space or in time. Most research is
      concentrated in western Europe, northern America and certain areas of Asia, while
      it is extremely limited or non-existent in Africa and most regions of the
      southern hemisphere. Marine mammals from the temperate fringe of the northern
      hemisphere, particularly fish-eating species which inhabit the mid-latitudes of
      Europe and North America, show the greatest organochlorine loads; noteworthy are
      the extremely high levels found in the Mediterranean Sea and certain locations on
      the western coasts of the United States. Concentrations in the tropical and
      equatorial fringe of the northern hemisphere and throughout the southern
      hemisphere are low or extremely low. The polar regions of both hemispheres showed
      the lowest concentrations of DDTs and PCBs, although levels of HCHs, chlordanes
      and HCB were moderate to high in the cold waters of the North Pacific. During
      recent decades, concentrations have tended to decrease in the regions where
      pollution was initially high but they have increased in regions located far from
      the pollution source as a consequence of atmospheric transport and
      redistribution. It is expected that the Arctic and, to a lesser extent, the
      Antarctic, will become major sinks for organochlorines in the future; this
      process may already be significant for some compounds such as HCB and HCHs.
      Effort should be devoted to both assessment of organochlorine trends in the now
      highly polluted populations of the temperate fringe of the northern hemisphere
      and to the implementation of long-term monitoring of marine mammal populations
      inhabiting polar regions.

PMID- 12054105
TI  - Trace metal uptake by the Chinese mitten crab Eriocheir sinensis: the role of
      osmoregulation.
AB  - Changes in salinity affect the bioavailability and consequent uptake of trace
      metals by euryhaline invertebrates. In many cases, salinity-related effects on
      metal uptake can be explained by changes in chemical speciation but salinity may
      also influence uptake indirectly through its action on osmoregulatory mechanisms.
      Specifically, it can be hypothesised that trace metal uptake may be reduced at
      salinities approaching the isosmotic point of a species because, at this point,
      there is reduced activity of ionic exchange pumps. The present study tested this
      hypothesis using the Chinese mitten crab, Eriocheir sinensis, a hyper
      hypoosmoregulator with an isosmotic point around 33 per thousand. Crabs were
      exposed to radio-labelled cadmium and zinc at 23, 33 and 43 per thousand for 4
      days. To eradicate speciation effects, crabs were exposed to the same
      concentration of the radio-labelled free metal ion (estimated using MineQL
      computer software) at each salinity. Haemolymph samples were taken daily and
      radio-labelled metal concentrations were estimated from radioactivity counts and
      used to provide relative measures of metal uptake. Neither cadmium nor zinc
      uptake was lowest at the isosmotic point. The uptake of cadmium increased
      significantly with increase in salinity, while the uptake of zinc showed no
      significant change with increased salinity. Thus changes in trace metal uptake
      rates in E. sinensis do not appear to be controlled only by changes in free metal
      ion concentrations. The different effects of salinity change on the uptake of
      cadmium and zinc (in the absence of free metal ion change) also indicate that
      physiological responses to osmotic change alone do not control metal uptake rates
      for this species.

PMID- 12054106
TI  - Reed (Phragmites australis) decline in a brackish wetland in Italy.
AB  - A comparative field study was carried out at two sites (a healthy site and a
      declining site) in a brackish wetland in northern Italy, with the objective to
      investigate the symptoms and the possible causes leading to reed (Phragmites
      australis) decline in this area. The declining reed plants presented many of the
      symptoms (clumping habit, smaller size, weaker culms, abnormal rhizome and root
      anatomy, low starch levels in rhizomes) comprised within the so-called reed die
      back syndrome, frequently observed in central European wetlands but never
      recorded previously in (Sub)Mediterranean regions. Soil nutrient levels did not
      differ much between the two sites, with nitrate concentrations in the soil being
      even higher at the healthy site (1.54 microg g(-1); die-back site 0.76 microg g(
      1)). Hence, eutrophication did not seem to represent a major cause in determining
      reed decline in this area. High sulphate concentrations in saltwater associated
      with low soil redox potentials (-215 mV) due to waterlogging resulted in high
      soil sulphide concentrations. Concentrations of organic acids, especially acetic
      acid, did not differ remarkably between sites. High sulphide levels presumably
      accounted for abnormal anatomical formations (callus blocking aerenchyma
      channels), lower rates of net CO2 exchange and reduced reserve storage, observed
      at the die-back site. This was associated with a lower mechanical resistance of
      reed culms which accelerated reed mortality in the die-back areas. We concluded
      that high sulpihde levels in permanently waterlogged soils may result in die-back
      of reed stands in Mediterranean wetlands.

PMID- 12054107
TI  - Evaluation of mine tailings effects on a benthic marine infaunal community over
      29 years.
AB  - Benthic infaunal and sediment data collected over 29 years were used to examine
      the extent and geographic range of effects and recovery from submarine tailings
      deposition. Empirical data were used to determine extreme and moderate effects,
      and identify near-, mid- and far-field zones. A simple probability test using
      overlap in frequency distributions was then used to determine less obvious
      effects, identify "normal" or "reference" conditions, and verify the geographic
      range of effect zones. Tailings thickness and sediment particulate copper were
      elevated from the outfall to 16-20 km distant, particularly below discharge depth
      (50 m). Changes in tailings thickness and copper levels before, during and after
      mining showed three distinct impact zones below discharge depth: near-field (<5
      km from outfall); mid-field (5-16 km); and far-field (20 + km). Consistent faunal
      declines during mining were noted at sediment particulate copper levels >300
      microg g(-1), and sediment tailings thickness > 15-20 cm. Extreme impoverishment
      at these sediment levels were; < 100 animals/m2, <2.5 g/m2 biomass and <7 taxa
      per station. No stations with >300 microg g(-1) copper and 20 cm tailings had
      more than 40 taxa. Amphipods were particularly affected by tailings, with
      distributions reflecting the instability in sediments from heavy deposition
      and/or shifting of tailings due to resuspension. The probability testing method
      assumed that reference conditions existed in far-field stations. There was no
      difference in abundance distributions between near-, mid- and far-field zones.
      Total taxa per station during mining was significantly reduced (<45) in both near
      and mid-field stations compared with far-field (less than 10% overlap in
      distributions). One midfield station in Quatsino Sound (23) was in reference
      condition throughout the study period. Post-closure stations in the near- and mid
      field had total taxa numbers approaching far-field conditions (overlap of 62% in
      distributions). Within 3 years following closure, total taxa values were within
      the far-field range for all stations sampled. Biomass showed a distinct decline
      in the near-field during mining, but with more overlap in near-field and far
      field distributions (27%) than for total taxa per station, and was returning to
      far-field conditions in the post-closure years. A multivariate (Bray-Curtis)
      measure of dissimilarity indicated that the near- and mid-field infaunal
      compositions were distinct from the far-field during mining (< 10% overlap in
      distributions). The mid-field composition overlapped more with the far-field in
      the post-closure years, but the near-field composition did not, suggesting that
      the mine tailings are still affecting the fauna. The most abundant taxon in each
      of the reference and near-field station groups both showed significantly distinct
      relative abundance distributions between near- and far-field stations. In
      summary, the probability method showed that species richness, biomass, species
      composition and indicator taxa were useful for differentiating affected and non
      affected stations. Polychaetes recolonize stable tailings most quickly, and have
      dominated the tailings stations in the post-closure years. Amphipods have
      recolonized sporadically, but seem to be highly sensitive to tailings stability.
      There was no evidence of recovery in dominant bivalves or echinoderms within
      three years after mine closure.

PMID- 12054108
TI  - Body height and weight of patients with childhood onset and adult onset
      thyrotoxicosis.
AB  - The present study has compared body height and weight of thyrotoxic female
      patients of childhood onset and adult onset. The body height of 141 out of 143
      (99%) adult-onset thyrotoxic patients was within the range of mean +/- 2SD for
      the age-matched general Japanese female population. On the other hand, in 42
      patients with childhood-onset thyrotoxicosis, 6 (14%) had their height being
      greater than the mean + 2SD of general population, and 34 (81%) were taller than
      the mean value. In 86 patients with siblings, 42 (49%) were at least 2 cm taller
      than their sisters, and 26 (30%) were more than 2 cm shorter than their sisters.
      The body weight of 27 out of 42 (68%) patients younger than 20 years was not
      decreased but was even greater than the mean value for the age-matched general
      population. The results indicate that excessive thyroid hormone in vivo enhances
      body height in humans. The increased body weight in some young patients suggests
      that enhanced dietary intake due to increased appetite in hyperthyroidism has
      overcome the energy loss with increased metabolism.

PMID- 12054109
TI  - MRI findings in the hypopharynx and the larynx of a patient with acromegaly
      associated with severe obstructive sleep apnea syndrome.

PMID- 12054110
TI  - Does hypopituitarism due to neurohypophyseal germinoma recover after
      chemotherapy?

PMID- 12054111
TI  - Insulin and EGF receptors integrate the Ras and Rap signaling pathways.
AB  - Ras is a low molecular weight (Mr 21,000) GTP binding protein that plays an
      essential role in cell proliferation and differentiation. Mutations that result
      in constitutive activation of Ras are associated with several types of neoplastic
      tissue in mammals and expression of these alleles into cultured fibroblasts
      results in cellular transformation. Opposing the Ras activation pathway, the low
      molecular GTP binding protein Rap was originally observed to revert or suppress
      the transformed phenotype in Ki-Ras-transformed fibroblasts. This apparent
      antagonism between Ras and Rap function may reflect the ability of Rap and Ras to
      interact with the same downstream effectors, since these proteins share identical
      sequences within their respective effector domains. Although the precise
      molecular details remained to be established, there is a substantial similarity
      in the upstream signaling mechanisms that regulate both Ras and Rap activation.
      Ras GTP binding is stimulated upon the targeting of the Ras guanylnucleotide
      exchange factor SOS to the plasma membrane location of Ras. The carboxyl terminal
      domain of SOS contains a proline-rich regions that directs its association with
      the SH3 domains of the small adapter protein, Grb2. Similarly, the formation of
      active GTP-bound Rap results from the specific interaction with the Rap
      guanylnucleotide exchange factor C3G which specifically associates with the
      central SH3 domain of the small adapter protein, CrkII. Thus, efficient
      regulation of receptor tyrosine kinase downstream signaling events require the
      coordinate interplay of these two pathways.

PMID- 12054112
TI  - A case of growth failure caused by 13-CIS-retinoic acid administration after bone
      marrow transplantation for neuroblasoma.
AB  - We report an 11-year-old girl with growth failure caused by long-term
      administration of 13-cis-retinoic acid after bone marrow transplantation for
      neuroblastoma. Her growth velocity was 1-2 cm/year after 13-cis-retinoic acid
      administration. Her endocrinological findings were normal except for peak growth
      hormone levels of 6.4 ng/ml (clonidine) and 9.7 ng/ml (arginine). IGF-1 and IGFBP
      3 were normal. It is not possible to conclude that her severe growth failure was
      caused by partial growth hormone deficiency, but premature epiphyseal closure was
      seen on radiographic examination. We concluded that the growth failure was caused
      by pediatric cancer therapy for the musculoskeletal system but not by
      endocrinological disturbance.

PMID- 12054113
TI  - Interaction between leptin and growth hormone (GH)/IGF-I axis.
AB  - In order to identify the mutual interaction between GH and leptin, we studied the
      effect of GH on fatty Zucker rats. GH administration at a high dose (5.0 IU/kg)
      reduced % body fat after 7 days. The leptin mRNA level in subcutaneous fat tissue
      was not changed but that in epididymal fat tissue was decreased by an even lower
      dose of GH (1.5 IU/kg). IGF-I treatment (200 microg/kg/day) did not change the %
      body fat or leptin mRNA level. These observations suggest that GH directly
      interacts with visceral fat and reduces fat mass and leptin expression. We also
      measured serum leptin levels in patients. The levels in patients with acromegaly
      were significantly lower than those in normal subjects with the same amount of
      body fat, but serum IGF-I and urinary C peptide excretion rates were higher in
      the acromegalic. These observations also suggests that GH directly interacts with
      adipose tissue and reduces leptin expression. Next we investigated the direct
      action of leptin on GH release from the pituitary. Leptin pretreatment of
      pituitary cells in culture or rats in a fasted or fed condition did not change
      GRH induced GH secretion. As indicated also by other recent studies, leptin may
      increase GRH or decrease somatostatin secretion by the hypothalamus. Thus GH
      interacts with fat tissues and leptin may be a good marker of the interaction.

PMID- 12054114
TI  - The mechanism of insulin-induced signal transduction mediated by the insulin
      receptor substrate family.
AB  - Distinct from other growth factor receptors, insulin and insulin-like growth
      factor-I (IGF-I) receptors phosphorylate endogenous substrates on tyrosine
      residues which in turn associate with the SH2 domain-containing proteins
      transducing signals to downstream pathways. Among the cellular substrates of
      insulin and IGF-I receptors, insulin receptor substrate (IRS)-1 has been shown to
      play an important role in mediating the actions of these hormones. Recently,
      several proteins with similar structures and different tissue distributions were
      cloned as IRS-2, -3 and -4. To study the roles of these IRSs in mediating insulin
      actions, we analyzed liver, muscle and adipocytes, the major targets of insulin
      actions, from IRS-1 null mice which we previously generated, and showed that: 1)
      insulin-stimulated activation of PI 3-kinase, mitogen-activated protein kinase
      and glucose transport were impaired in muscles from IRS-1 null mice which was in
      contrast to the grossly normal signaling and actions in livers from these mice;
      2) the difference in the degree of insulin resistance in these two major insulin
      targets appeared to depend on the amount of tyrosine phosphorylation of IRS-2
      compensating for IRS-1 deficiency; 3) insulin-induced activation of PI 3-kinase,
      glucose transport and GLUT4 translocation were impaired but not abolished in
      adipocytes from these mice in which IRS-3 was the major tyrosine-phosphorylated
      protein activating PI 3-kinase and at least partially mediating some residual
      insulin actions in the absence of IRS-1. These data suggest that the members of
      the IRS family redundantly regulate insulin actions in each target organ in a
      distinct fashion.

PMID- 12054115
TI  - Long-term effect of growth hormone (GH) treatment on body composition in children
      with GH deficiency.
AB  - OBJECTIVE: It is important for GH-deficient children to treat abnormal body
      composition associated with a metabolic consequence, not only short stature. In
      this study we evaluated long-term effects of GH therapy on body composition in GH
      deficient boys and girls. SUBJECTS AND METHODS: Forty-nine subjects with GH
      deficiency, 35 boys and 14 girls, 6 to 14 years of age, were studied. All the
      subjects were treated for three years with recombinant human GH at a weekly
      dosage of 0.5 IU/kg by subcutaneous daily injection. Body composition was
      measured by bioelectrical impedance analysis (BIA 101, Spectrum II 287, RJL
      Systems, Detroit, Mich). RESULTS: Body fat (%) decreased significantly during the
      first three months of GH treatment. These values were maintained low thereafter
      in boys, in contrast to those which continued to tend upward in girls from the
      second year of the treatment. Lean body mass (kg) increased significantly with
      increasing extracellular water (kg) and body cell mass (kg) in both sexes during
      GH treatment. CONCLUSION: Our data demonstrate that GH can reduce body fat mass
      in GH-deficient boys and girls. The gender difference in changes in body fat with
      age during the course of this study is compatible with that observed in normal
      children. The rapid increase in extracellular water and the gradual increase in
      body cell mass both contributed to the steady increase in LBM during GH
      treatment.

PMID- 12054117
TI  - Growth of two children after six months interruption of GH therapy.
AB  - We describe two short boys with normal GH responses to the stimuli in whom GH
      therapy was interrupted for 6 months. Their growth rates before and after the
      interruption, and after re-administration of GH were evaluated. Height velocity
      (HV) in case 1 before and after the interruption was 6.6 cm/y and 5.0 cm/y,
      respectively. HV was not increased (5.0 cm/y) by re-initiation of GH therapy
      despite the high serum IGF-1 level. Height velocity (HV) in case 2 before and
      after the interruption was 5.6 cm/y and 3.6 cm/y, respectively. HV was slightly
      increased to 4.1 cm/y by re-administration of GH, but it was far below the
      pretreatment value. Serum IGF-1 was increased by GH in this case as well. We
      conclude that re-acceleration of growth by re-administration of GH after
      interruption of therapy, as seen in classical GHD patients, may not be expected
      in normal short children.

PMID- 12054116
TI  - Continuous subcutaneous infusion of recombinant human growth hormone (rhGH)
      improved renal function in a patient with Sheehan's syndrome associated with
      chronic renal failure.

PMID- 12054118
TI  - Normal growth after administration of octreotide: report on a case of persistent
      hyperinsulinemic hypoglycemia of infancy treated by continuous subcutaneous
      injection of octreotide.

PMID- 12054119
TI  - Cardiac effects of growth hormone in physiology and in heart failure.

PMID- 12054120
TI  - Pharmacological treatments for GH-induced insulin resistance.
AB  - Troglitazone (T) and d-chiroinositol (DCI) have been reported to improve insulin
      resistance associated with obesity and NIDDM. We tested whether these compounds
      counteract the insulin antagonistic effects of recombinant human GH. Male Wistar
      rats were allocated to 4 different treatment groups, rhGH (n=8), rhGH+T (n=7),
      rhGH+DCI (n=8) and control (saline, n=8). rhGH (2 IU/100 g/day) was injected sc
      twice daily for 2 days. T and DCI were given (20 mg/day) po for 5 days preceding
      and 2 days along with rhGH. Euglycemic hyperinsulinemic clamp studies were done
      to assess the hepatic glucose output (HGO) and glucose disappearance rate (GDR).
      Fasting plasma glucose, insulin, serum FFA and basal HGO were similar in all 4
      treatment groups. During the hyperinsulinemic clamp which raised plasma insulin
      levels to 7.2 +/- 0.4 ng/ml, HGO was suppressed in the control and rhGH+T treated
      rats but not in the rats treated with rhGH and rhGH+DCI. GDR decreased in the
      rats which received rhGH (18.1 +/- 5.8 vs 30.3 +/- 5.2 mg/kg/min) compared to the
      control rats. The rats given either T (24.7 +/- 2.7) or DCI (31.4 +/- 2.7) along
      with rhGH showed comparable GDR to the control rats. These results indicated that
      rhGH induced hepatic and peripheral insulin resistance. Troglitazone counteracted
      the insulin-antagonistic action of rhGH both in the liver and the peripheral
      tissues. DCI was effective in offsetting peripheral insulin resistance but
      without any effect on hepatic insulin resistance associated with rhGH treatment.

PMID- 12054121
TI  - Decreased bone mineral density during GnRH analog therapy and polymorphism of
      estrogen receptor gene in precocious puberty.

PMID- 12054122
TI  - IGF-1 regulates migration and angiogenesis of human endothelial cells.
AB  - Recent studies revealed favorable para- and/or autocrine effects of IGF-1 in the
      pathogenesis of diabetic complications. On the other hand, hyperglycemia is a
      risk factor for the development of diabetic vascular complications. In this study
      we examined the effects of high glucose and/or IGF-1 on cell migration and
      angiogenesis (tubular formation) by using human endothelial cells (EC) in vitro.
      First we examined cell migration by the two-chamber method. Chronic treatment
      with a high concentration of D-glucose strongly stimulated the cell migration,
      which was mimicked by PMA, a protein kinase C (PKC) agonist. The cell migration
      was also induced by IGF-1. The glucose-induced cell migration was blocked by PKC
      inhibitor, H7. IGF-1-induced cell migration was not blocked by PD98059, MAPK/ERK
      kinase (MEK) inhibitor or wortmannin, a phosphatidylinositol (PI) 3-kinase
      inhibitor. Next we examined the effects of high glucose and/or IGF-1 on the
      tubular formation of EC. The tubular formation was induced only when the cells
      were exposed to a combination of high glucose and IGF-1. The tubular formation
      was blocked by MEK inhibitor and PI 3-kinase inhibitor but not by PKC inhibitor.
      These results indicate that hyperglycemia and IGF-1, respectively, stimulate the
      EC migration, and tubular formation is induced by a combination of IGF-1 and
      hyperglycemia.

PMID- 12054123
TI  - Effect of cytokines on production of insulin-like growth factor binding proteins
      (IGFBPs) from human fibroblasts in culture.
AB  - Bioactivity of Insulin-like growth factors (IGEs) are positively or negatively
      regulated by IGF binding proteins (IGFBPs). Like IGFs, production of IGFBPs are
      influenced by a number of hormonal factors. We studied the effects of cytokines
      on production of IGFBPs in human fibroblasts in culture. Both IL-1beta and TNF
      alpha inhibited IGFBP-3 (42/38 KDa species) production in a concentration
      dependent manner judged by Western ligand blot. Expression of IGFBP-3 mRNA was
      also decreased by these cytokines. Moreover, the treatment with IL-1beta and TNF
      alpha resulted in appearance of smaller mol weight (26 KDa) immunoreactive IGFBP
      3 fragment(s) which lacked the ability to bind 125I-IGFs, indicating that these
      cytokines degrade IGFBP-3 via activation of proteases. Both IL-1beta and TNF
      alpha decreased production of IGFBP-4, whereas they increased that of IGFBP-6, IL
      6 had little effect on production of IGFBPs. Likewise, interferon-gamma failed to
      affect of production of IGFBPs except at high concentrations. The present data
      demonstrate that cytokines, especially IL-1beta and TNF-alpha are potent
      regulators of IGFBPs production and degradation. These cytokines may alter tissue
      uptake of IGFs and help to counteract the catabolic state induced by them.

PMID- 12054125
TI  - Screening for mutations in the GH-1 gene by dideoxy fingerprinting (ddF).

PMID- 12054124
TI  - The involvement of growth hormone-binding protein in altered GH-IGF axis in IDDM.
AB  - High GH and low IGF-I are well known in IDDM patients. To delineate this altered
      GH-IGF-I axis in IDDM, we investigate the role of GH-binding protein (GHBP) in
      relation to the metabolic and nutritional states. MATERIALS AND METHODS: Forty
      seven patients with IDDM, mean 13.7 years, were evaluated. Blood samples were
      obtained before insulin injection and breakfast to test for plasma glucose (PG),
      IGF-I, IGFBP-1, IGFBP-3, total and complex GHBP (tGHBP and cGHBP), and HbA1c.
      Urine samples were collected in the morning for urinary GH (uGH). The difference
      between tGHBP and cGHBP is defined as fGHBP. The levels of PG and HbA1C were not
      correlated with each level of tGHBP, cGHBP, fGHBP or uGH. The levels of tGHBP,
      cGHBP and fGHBP were not all correlated with uGH. Both the levels of IGF-I and
      body mass index (BMI) were positively correlated with fGHBP. The duration of IDDM
      was negatively correlated with tGHBP, cGHBP and fGHBP. DISCUSSION: As the
      previous report of the relationship between GH binding reserve to GHBP and IGF-I
      or BMI in non-diabetic subjects, fGHBP again showed statistical links with these
      parameters in IDDM. We therefore suggest that GHBP, especially its free form, may
      reflect a malmetabolic state of IDDM liver, resulting in an altered GH-IGF-I
      axis.

PMID- 12054126
TI  - Functional expression of human growth hormone (hGH) transgene in the rat
      somatotroph.

PMID- 12054127
TI  - Silent somatotroph adenoma, detected by catalyzed signal amplification and non
      radioisotopic in situ hybridization.

PMID- 12054128
TI  - Stimulation of growth hormone gene expression in the pituitary and brain by Panax
      ginseng C. A. MEYER.

PMID- 12054129
TI  - Effect of growth hormone on growth failure and bone loss induced by
      supraphysiologic dose of glucocorticoid in rats.

PMID- 12054130
TI  - Regulation of body fluid balance in spontaneous dwarf rats caused by isolated
      growth hormone (GH) deficiency.

PMID- 12054132
TI  - Bid to save MSc teaching at the CTVM. Centre for Tropical Veterinary Medicine.

PMID- 12054131
TI  - Setting up an automated system for evaluation of bone age.
AB  - The "Tanner-Whitehouse 2" method is the most popular in evaluating skeletal
      maturation, but this method has some inherent weak points. We therefore developed
      the new system to automatically evaluate the skeletal maturation of Japanese
      children by means of a personal computer. The subjects of this study were 318
      healthy Japanese boys and 199 girls ranging from 2 to 15 years of age. The bone
      age was calculated by multiple regression analysis with parameters for the
      epiphysis and metaphysis. Successful automatic evaluation was about 80-90% on
      each phalanx. There was a significant correlation between chronological age and
      the ratio of epiphyseal width to metaphyseal width. The system developed in this
      study was useful for evaluating the skeletal maturation.

PMID- 12054133
TI  - Antimicrobial resistance in Salmonella isolated from animals and their
      environment in England and Wales from 1988 to 1999.
AB  - Resistance to 16 antimicrobial agents was monitored in 109,125 Salmonella
      cultures isolated from animals, their environment and feedstuffs between 1988 and
      1999. The sensitivity of the 6512 isolates of Salmonella enterica enterica
      serotype Dublin to all the antimicrobial agents tested varied from 98.2 per cent
      in 1997 to 99.7 per cent in 1990 and 1996. In contrast, among 28,053 isolates of
      Salmonella enterica enterica serotype Typhimurium, there was a marked decrease in
      their sensitivity to all the antimicrobial agents tested, from 57.4 per cent in
      1992 to 7.6 per cent in 1995, owing to the widespread occurrence in farm animals
      of S Typhimurium isolates of the definitive type DT104, resistant to ampicillin,
      sulphonamides, streptomycin, chloramphenicol and tetracyclines, although the
      percentage of sensitive isolates increased to 18.4 per cent in 1999, when the
      incidence of DT104 had decreased. Some isolates of DT104 also showed an increase
      in resistance to potentiated sulphonamides (2.4 per cent in 1989 to 19.2 per cent
      in 1999) and nalidixic acid (0 per cent in 1992, 3.8 per cent in 1995 to a peak
      of 16.9 per cent in 1998). In 1996, 5.1 per cent of 1086 isolates of S
      Typhimurium from cattle and 35.9 per cent of 192 isolates of S Typhimurium from
      poultry showed resistance to nalidixic acid. Of the other 74,528 Salmonella
      isolates, the percentage of strains sensitive to all the antimicrobials tested
      decreased slightly from 88.2 per cent in 1988 to 70.6 per cent in 1996 and then
      increased slightly to 73.7 per cent in 1999. The commonest of these other
      Salmonella serotypes was Salmonella Enteritidis (20,982), which remained
      predominantly susceptible (ranging from 81.4 to 97.4 per cent) during the study
      period. Few isolates were resistant to commonly used veterinary antimicrobials,
      for example, furazolidone, the use of which was banned in 1990, and the
      aminoglycoside, apramycin.

PMID- 12054134
TI  - Evaluation of measurements of the conductivity of quarter milk samples for the
      early diagnosis of mastitis.
AB  - Measurements of the conductivity of quarter milk samples were made in 31 cows in
      a 70-cow herd in southeast England, for a period of 15 weeks. Over this period,
      42 per cent of cow-weeks and 20 per cent of quarter-weeks had an increase in
      quarter milk conductivity of 10 per cent of more compared with the mean
      conductivity of the previous 14 milkings. Fourteen per cent of quarter-weeks had
      an increase in conductivity of 15 per cent or more. The geometric mean somatic
      cell count (cell count) was higher in quarter-weeks with a 10 per cent or greater
      increase in conductivity than in quarter-weeks with a conductivity change of less
      than 10 per cent. At a conductivity threshold of 10 or 15 per cent and a cell
      count threshold of 200,000 or 400,000 cells/ml the specificity of this system was
      estimated to be 85 to 92 per cent, the sensitivity 40 to 54 per cent, the
      negative predictive value 87 to 93 per cent and the positive predictive value 33
      to 55 per cent. The positive predictive value of the individual quarter milk
      conductivity was insufficiently accurate to be used as the sole criterion for the
      selection of quarters for early antibiotic treatment.

PMID- 12054135
TI  - Infectious agents associated with respiratory disease in pheasants.
AB  - In a case-control study of the infectious agents associated with natural
      outbreaks of respiratory disease in pheasants, 28 batches of birds from sites
      affected by disease and eight batches of birds from unaffected sites were
      examined by six veterinary laboratories in England, Wales and Scotland, and
      tested for mycoplasmas, other bacteria and viruses. Sinusitis was the commonest
      sign of disease and was associated with Mycoplasma gallisepticum as detected by
      PCR in the trachea (P < 0.05) and conjunctiva (P < 0.01). Sinusitis was also
      associated with pasteurella cultured from the sinus (P < 0.05), antibody to avian
      pneumovirus (APV) (P < 0.01) and avian coronaviruses as detected by reverse
      transcriptase PCR (P < 0.05); there was no association between disease and APV as
      detected by PCR. Avian coronaviruses were the most common infectious agents
      detected. They were genetically close to infectious bronchitis virus (IBV) but
      differed in their gene sequence from all the serotypes of IBV previously
      identified in domestic fowl, and serological tests with six known IBV types
      showed little cross reactivity. Mycoplasma species other than M gallisepticum
      were cultured in 18 batches of pheasants but, with the exception of Mycoplasma
      gallinaceum, were not associated with disease.

PMID- 12054136
TI  - Coronary band dystrophy in two horses.
AB  - Two mature large-breed horses with coronary band dystrophy and chorioptic mange
      are described. They both had clinical signs of coronary band scaling and crusting
      but were not lame. Coronary band dystrophy can be differentiated from similar
      clinical conditions on the basis of the histological appearance of skin biopsy
      specimens, and by the exclusion of other possible disease processes. Its
      aetiology is uncertain, but probably involves a localised defect of
      keratinisation affecting the specialised epithelium of the coronary band.

PMID- 12054137
TI  - Investigation into the potential pathogenicity of Staphylococcus felis in a cat.

PMID- 12054138
TI  - Supply of POMs.

PMID- 12054139
TI  - Supply of POMs.

PMID- 12054140
TI  - Supply of POMs.

PMID- 12054141
TI  - Village pounds.

PMID- 12054142
TI  - RCVS Council elections.

PMID- 12054143
TI  - Palliative care and geriatric medicine: shared concerns, shared challenges.

PMID- 12054144
TI  - Home palliative care as a cost-saving alternative: evidence from Catalonia.
AB  - The aim of this study was to provide a comparative assessment of the health care
      resources consumed during the final month of life of patients undergoing
      palliative treatment and who died from cancer in the town of Mataro, Spain, in
      1998, with respect to whether they benefited from home care teams or not.
      Relevant differences in the use of health care resources were found between the
      groups. Patients in the standard care group presented more hospital care
      admissions and longer length of stay, higher use of emergency and outpatient
      visits, and greater use of palliative care units within nursing homes than
      patients in the home care group. The monetary quantification of the use of the
      above-mentioned resources showed a 71% increase in the cost per patient in the
      standard care when compared to home care. According to the results of this study,
      home care teams for terminal cancer patients allow for savings to the health care
      system. A series of policy making and health services research implications are
      discussed.

PMID- 12054145
TI  - The concerns of patients under palliative care and a heart failure clinic are not
      being met.
AB  - Patients with a terminal illness, identified by palliative care teams working in
      Manchester, and patients attending a heart failure clinic, were asked to
      participate in a prospective survey to determine their main concerns. Data were
      collected from 213 palliative care (PC) patients (mostly with cancer) and 66
      patients with heart failure (HF). The median ages of the two patient groups were
      similar, but the HF patients were more likely to be male and living with a
      partner; 13% of PC and 7% of HF patients reported that they had no carer. The PC
      patients had more district nurse, hospice, social work and physiotherapy input.
      The most frequently reported troublesome problems for PC patients were pain
      (49%), loss of independence (30%) and difficulty walking (27%). HF patients
      reported dyspnoea (55%), angina (32%) and tiredness (27%) as the most troublesome
      problems. From a checklist of symptoms, the frequency of tiredness (PC = 77%, HF
      = 82%) and difficulty getting about (PC = 71%, HF = 65%) were high in each group.
      Psychological problems were reported by 61% of PC and 41% of HF patients. Cardiac
      patients reported more breathlessness and cough than PC patients (83% vs 49% and
      44% vs 26%, respectively). Reduced libido was more common in cardiac patients
      (42% vs 21%). Patient disclosure of troublesome problems to professional carers
      was high (>87% in both PC and HF patients). Documented action was greater for
      physical than social or psychological problems. For PC patients, documented
      action was recorded for 83% physical, 43% social/functional and 52% psychological
      problems. For HF patients documented action was recorded for 74% cardiac, 60%
      physical - non-cardiac, 30% social/functional and 28% psychological problems.
      Clearly many patients' troublesome problems were not being addressed. As a result
      of this study, specific action by health care professionals was taken in 50% of
      PC patients and 71% of HF patients. We plan to target specific educational events
      on the treatment of physical problems, psychological assessment and social
      service provision.

PMID- 12054146
TI  - A comparison of the palliative care needs of patients dying from chronic
      respiratory diseases and lung cancer.
AB  - This paper reports on data from the Regional Study of Care for the Dying,
      conducted in 1990, and compares symptoms, care and service utilization for
      patients with chronic lung diseases (CLD) and lung cancer (LC) in the final 12
      months of life. Post-bereavement structured interviews were conducted with
      informal carers of 449 LC patients and 87 CLD patients. The LC patients were
      significantly younger than those with CLD (P = 0.001) and these respondents were
      more likely to have been a spouse (P = 0.034). No differences were found in the
      mean number of symptoms reported by the two groups in the final year or week of
      life, although the CLD patients were more likely to have experienced these
      symptoms for longer. Significantly more patients with CLD than LC experienced
      breathlessness in the final year (94% CLD vs 78% LC, P < 0.001) and final week
      (91% CLD vs 69% LC, P < 0.001) of life. Significantly more LC patients were
      reported to have experienced anorexia (76% LC vs 67% CLD, P = 0.06) and
      constipation (59% LC vs 44% CLD, p = 0.01) in the final year of life. There were
      no differences in general practitioner use, but LC patients were reported to have
      received more help from district nurses (52% LC vs 39% CLD, P = 0.025) and from a
      palliative care nurse (29% LC vs 0% CLD, P < 0.001). More CLD patients were
      reported to have received help from social services (29% CLD vs 18% LC, P =
      0.037). LC patients were reported to be more likely to have known they might die
      (76% LC vs 62% CLD, P = 0.003) and to have been told this by a hospital doctor
      (30% LC vs 8% CLD, P = 0.001). Among those that knew, LC patients were told
      earlier prior to death than CLD patients. This study suggests that patients with
      CLD at the end of life have physical and psychosocial needs at least as severe as
      patients with lung cancer.

PMID- 12054147
TI  - The role of disodium pamidronate in the management of bone pain due to
      malignancy.
AB  - A number of controlled studies have recently demonstrated the role of disodium
      pamidronate in the prevention of skeletal complications in patients with
      metastatic bone disease due to breast cancer and multiple myeloma. They have also
      shown that it relieves pain and is well tolerated. The aim of this open
      prospective study was to evaluate the acceptability of a new schedule of
      pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky
      Performance Status (KPS) in patients with metastatic bone pain treated with
      pamidronate in association or not with chemotherapy, radiotherapy, and hormone
      therapy. Patients with different types of cancer and at least one painful bone
      metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate
      weekly for three consecutive doses, with a 3-week interval between the two cycles
      (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total
      of 24 infusions. Two hundred patients were enrolled in the study, of whom 94
      received at least the first six infusions; 25 patients received all 24 infusions.
      Pamidronate was well tolerated in the majority of the patients both during the
      first six infusions and during the whole study period. In the patients under
      study, pain intensity decreased compared with T0 after the first two infusions
      (second week of treatment). The mean equivalent daily dose of oral morphine
      required ranged from 21.5 to 41.5 mg/day and was low and stable during the study.
      For the patients who remained in the study, the KPS remained around 70 during the
      whole treatment period and intrasubject analysis showed a substantial stability
      of the KPS within each subject. A first fracture occurred within 321 days in 25%
      of the whole population under study. Pamidronate represents a further valid
      therapy to add to an already consolidated list of therapies such as radiotherapy,
      chemotherapy, hormone therapy and orthopaedic intervention in the pain management
      of patients with bone metastases. Future studies are necessary to evaluate the
      role of pamidronate and the appropriate schedule in patients with advanced or
      terminal cancer who are no longer being treated with oncological therapies.

PMID- 12054148
TI  - Transdermal fentanyl for the management of cancer pain: a survey of 1005
      patients.
AB  - Transdermal fentanyl was released in Germany in 1995. From October 1996 to
      February 1998 transdermal treatment was documented for 1005 patients (506 men and
      499 women with a mean age of 60 years, range 20-92 years) with chronic pain in an
      open survey including 290 physicians from hospitals and general practitioners
      throughout Germany. Most patients suffered from cancer pain and only 11 patients
      had chronic pain from non-malignant disease. Physicians were asked to complete a
      questionnaire for patients treated with transdermal fentanyl on initiation of
      therapy (day 0), and days 3, 6, 18, 30 thereafter, followed by monthly follow-up
      intervals. Patients were asked to complete a pain diary. Transdermal therapy was
      documented from day 0 for 824 patients, while 181 patients had been treated with
      transdermal fentanyl before admission in the survey. Most of the other 824
      patients had been treated with other step 3 opioids (55% of the patients) or step
      2 opioids (23%) before conversion to transdermal fentanyl, whereas 8% had been
      treated only with non-opioids and 14% had received analgesics only as required or
      not at all before initiation of transdermal therapy. The most important reasons
      for switching to transdermal opioid therapy were insufficient pain relief with
      the previous medication followed by a variety of gastrointestinal symptoms
      impeding oral analgesic therapy. Initial fentanyl doses ranged from 0.6 to 9.6
      mg/day (25 to 400 microg/h) with a median of 1.2 mg/day (50 microg/h). Median
      doses slowly increased throughout the observation period to 2.4 mg/day (100
      microg/h) after 4 months of treatment. Most patients continued transdermal
      therapy until the time of death (47% of patients). Other reasons for
      discontinuation were inadequate pain relief (10%), pain relief with other
      analgesic regimens (10%), other symptoms than pain (5%), rejection of transdermal
      therapy by the patient (6%) or miscellaneous (16%). Adverse events were
      documented as the reason for discontinuation of transdermal therapy in 49
      patients (5%). Dyspnoea was documented for seven patients as the reason for
      discontinuation. One of these patients, as well as another patient with an
      episode of apnoea, had to be treated with artificial respiration for several
      hours, but both patients recovered without sequelae. Transdermal therapy with
      fentanyl was safe and efficient in this national survey. Transdermal fentanyl can
      be recommended for treatment of moderate to severe cancer pain and probably may
      even be used as a first-line drug on step 3 of the World Health Organization
      recommendations in selected patient groups.

PMID- 12054149
TI  - Sublingual fentanyl citrate for cancer-related breakthrough pain: a pilot study.
AB  - The effects of sublingual fentanyl citrate (SLFC) were assessed in 11 hospice
      inpatients with cancer-related breakthrough pain. Patients were asked to rate
      their pain, using a visual analogue scale, before SLFC, then after 3, 5, 10, 15,
      30, 45 and 60 min. Six patients (55%) had reductions in pain scores at 10 min and
      nine patients (82%) at 15 min. Ratings for SLFC were very good (18%), good (36%),
      moderate (28%), and bad (18%). Compared to the usual breakthrough medication,
      SLFC was better (46%), the same (36%), or worse (18%). Advantages of SLFC
      included ease of use, quick onset of action and no associated drowsiness. No
      systemic adverse events were noted, but two patients reported dry mouth and two a
      bitter taste. Two patients found it difficult to retain the medication under the
      tongue. Seven patients (64%) said they would continue to use SLFC. Sublingual
      fentanyl citrate appears safe and well tolerated by these patients. Randomized
      placebo-controlled and dose ranging studies are required to confirm these
      findings.

PMID- 12054150
TI  - A study comparing hyoscine hydrobromide and glycopyrrolate in the treatment of
      death rattle.
AB  - This study looked at the efficacy of drug treatment in managing death rattle in a
      30-bedded specialist palliative care unit. The study was conducted in two phases.
      In the first, patients received hyoscine hydrobromide as the antimuscarinic;
      glycopyrrolate was used in the second phase. The patients in the two phases were
      well matched for diagnosis, age, sex and duration of death rattle. A noise score
      scale of 0-3 was used, which was separately validated using a verbal rating scale
      and noise-meter readings. Noise scores were taken at the start; 30 min after an
      antimuscarinic drug was administered; an hour after the initial injection if a
      repeat dose was given at 30 min; and 4-hourly thereafter. Drug charts of all
      patients with death rattle were analysed to ascertain the amount of each drug
      given and the cost. The incidence of death rattle was 44% in phase I, and 36% in
      phase II. The percentage of patients with reduced noise scores 30 min after one
      injection of hyoscine was significantly greater than after one dose of
      glycopyrrolate (56% vs 27%, P = 0.002). The need for a second injection after 30
      min was less using hyoscine (33% vs 50%, P = 0.03). There was no statistically
      significant difference in improvement at 1 h, or at the last recorded score
      before death. A comparison of the cost of drug treatment using hyoscine or
      glycopyrrolate was made, and the potential reduction in cost per patient in the
      glycopyrrolate group was largely offset by increased expenditure on other drugs,
      especially diamorphine, midazolam and levomepromazine. The results of this study
      suggest that: (1) glycopyrrolate 0.2 mg is less effective at reducing death
      rattle than hyoscine hydrobromide 0.4 mg when assessed at 30 min, (2) the use of
      glycopyrrolate may lead to an increased need for other sedative or anti-emetic
      medication such as diamorphine, midazolam or levomepromazine, and (3) the cost
      benefit of using glycopyrrolate over hyoscine hydrobromide is a small part of the
      total drug budget, and may be less than anticipated due to the increased need of
      these other drugs.

PMID- 12054151
TI  - Accounts of carers' satisfaction with health care at the end of life: a
      comparison of first generation black Caribbeans and white patients with advanced
      disease.
AB  - While much research has described experiences at the end of life, no studies have
      explored the black Caribbean perspective. This paper compares the final year of
      life of first generation black Caribbeans and white patients with advanced
      disease in an inner London health authority, focusing on their satisfaction with
      service provision in both primary care and acute settings using face-to face
      interviews with carers of deceased patients. Of the 106 black Caribbean patients
      and 110 white deceased patients identified as dying during the study period 50
      interviews per ethnic group were conducted with family members or close friends,
      a response rate of 47% and 45%. Even though examples of excellent and good care
      were cited, a larger proportion of negative satisfaction ratings of health care
      was recorded among respondents representing black Caribbean patients. This was
      true for all health care settings, particularly primary care, but less so for
      specialist palliative care nurses. However, few black Caribbean patients accessed
      specialist palliative care nurses or hospices. Qualitative data provided a deeper
      insight into the black Caribbean experience care at the end of life. We recommend
      that where examples of best practice in palliative care and culturally sensitive
      provision are evident they be extended to more health care professionals through
      education and training. Access to specialist palliative care services needs to be
      improved.

PMID- 12054152
TI  - The use of sedatives at the end of life.

PMID- 12054153
TI  - A simple method of using epidural analgesia in palliative medicine.

PMID- 12054154
TI  - Gabapentin: resistant neuropathic pain and malignancy.

PMID- 12054155
TI  - Overexpression of Dlx5 in chicken calvarial cells accelerates osteoblastic
      differentiation.
AB  - Our laboratory and others have shown that a homeodomain protein binding site
      plays an important role in transcription of the Collal gene in osteoblasts. This
      suggests that homeodomain proteins have an important role in osteoblast
      differentiation. We have investigated the role of Dlx5 in osteoblastic
      differentiation. In situ hybridization studies indicated that Dlx5 is expressed
      in chick calvarial osteoblasts (cCOB) in vivo. Northern blot analysis indicated
      that Dlx5 expression in cultured cCOBs is induced concurrently with osteoblastic
      markers. To study the effect of overexpression of Dlx5 on osteoblast
      differentiation, we infected primary osteoblast cultures from 15-day-old
      embryonal chicken calvaria with replication competent retroviral vectors
      [RCASBP(A)] expressing Dlx5 or control replication competent avian splice
      acceptor brianhightiter polymerase subtype A [RCASBP(A)]. Expression of Collal,
      osteopontin, alkaline phosphatase, and osteocalcin messenger RNA (mRNA) occurred
      sooner and at higher levels in cultures infected with RCASBP(A)DLX5 than in
      RCASBP(A)-infected cultures. Mineralization of Dlx5-expressing cultures was
      evident by days 12-14, and RCAS-infected control osteoblasts did not begin to
      mineralize until day 17. Dlx5 also stimulated osteoblastic differentiation of
      calvarial cells that do not normally undergo osteoblastic differentiation in
      vitro. Our results suggest that Dlx5 plays an important role in inducing
      calvarial osteoblast differentiation.

PMID- 12054156
TI  - Role of inducible nitric oxide synthase in skeletal adaptation to acute increases
      in mechanical loading.
AB  - To clarify the role of nitric oxide (NO) in regulation of bone metabolism in
      response to skeletal loading, we examined inducible NO synthase (iNOS) gene
      knockout mice in the tail-suspension model. Histomorphometric analyses of
      proximal tibias revealed that 7 days of tail suspension decreased the bone volume
      (BV/TV) and bone formation rate (BFR/BS) and increased the osteoclast surface
      (Oc.S/BS) in mice with all iNOS genotypes. Both iNOS+/+ and iNOS+/- mice
      responded to subsequent 14-day reloading, with increases in BV/TV and BFR/BS and
      a decrease in Oc.S/BS, whereas these responses were abolished in iNOS-/- mice.
      The osteoblasts flattened after tail suspension appeared cuboidal during
      subsequent reloading. Immunoreactivity for iNOS was detected in these osteoblasts
      and osteocytes by immunohistochemistry. These defective responses after reloading
      were rescued in iNOS-/- mice by treatment with an NO donor nitroglycerine (NG).
      Conversely, the responses in iNOS+/+ mice were inhibited by treatment with an NOS
      inhibitor aminoguanidine (AG). In bone marrow cell cultures, mineralized nodules
      derived from iNOS-/- mice after reloading were significantly reduced. Taken
      together, our results suggest that NO generated by iNOS in osteoblasts plays a
      critical role in adjusting bone turnover and increasing osteogenic activity in
      response to the acute increase in mechanical loading after tail suspension.

PMID- 12054157
TI  - Enhancing effect of Tob deficiency on bone formation is specific to bone
      morphogenetic protein-induced osteogenesis.
AB  - Tob is a recently reported novel bone morphogenetic protein (BMP) inhibitor,
      which originally was identified by West-Western procedure using ErbB2 as a probe
      and contains a nuclear localization signal. To further characterize the effects
      of Tob deficiency on BMP-induced new bone (NB) formation, we examined
      microcomputed tomography (microCT) on the cross-section of the bone induced by
      daily injection with BMP onto the calvariae of newborn mice. The calvariae of the
      saline-injected Tob-deficient (TD) mice were similar to those of the saline
      injected or untreated wild-type (WT) mice. BMP injection locally produced NB on
      the calvaria in WT mice as known previously. In contrast to WT mice, BMP
      injection onto the calvariae of TD mice produced a calcified area in the cross
      section of NB, which was more than that produced by BMP in the WT calvariae. In
      addition, the horizontal width and the vertical height of the NB induced by BMP
      in TD mice were several-fold more than those in WT mice. The effect of Tob
      deficiency on bone-forming activity was selective to the response to the
      injection with BMP because the levels of injury-induced NB formation examined by
      microCT 10 days after bone marrow ablation in the femora were similar between the
      TD and WT mice. These data indicate that Tob acts as a novel specific antagonist
      against bone formation induced by BMP treatment in bone.

PMID- 12054158
TI  - Leptin acts as a growth factor on the chondrocytes of skeletal growth centers.
AB  - Childhood obesity frequently is associated with an increase in height velocity
      and acceleration of epiphyseal growth plate maturation despite low levels of
      serum growth hormone (GH). In addition, obesity is associated with higher
      circulating levels of leptin, a 16-kDa protein that is secreted from the
      adipocytes. In this study, we evaluated the direct effect of leptin on the
      chondrocyte population of the skeletal growth centers in the mouse mandibular
      condyle, a model of endochondral ossification. We found that chondrocytes in the
      growth centers contain specific binding sites for leptin. Leptin, at a
      concentration of 0.5-1.0 microg/ml, stimulated in a dose-dependent manner the
      width of the chondroprogenitor zone (up to 64%), whereas higher concentrations
      had an inhibitory effect. Leptin induction of both proliferation and
      differentiation activities in the mandibular condyle was confirmed by our
      findings of an increase in bromodeoxyuridine (BrdU) incorporation into DNA and in
      (acidic) Alcian blue (AB) staining of the cartilaginous matrix. Leptin also
      increased the abundance of the insulin-like growth factor (IGF) I receptor and
      IGF-I receptor messenger RNA (mRNA) within the chondrocytes and the progenitor
      cell population. Our results indicate that leptin acts as a skeletal growth
      factor with a direct peripheral effect on skeletal growth centers. Some of its
      effects on the growing bone may be mediated by the IGF system via regulation of
      IGF-I receptor expression. We speculate that the high circulating levels of
      leptin in obese children might contribute to their growth.

PMID- 12054159
TI  - Changes in bone structure and mass with advancing age in the male C57BL/6J mouse.
AB  - To determine whether the mouse loses bone with aging and whether the changes
      mimic those observed in human aging, we examined the changes in the tibial
      metaphysis and diaphysis in the male C57BL/6J mouse over its life span using
      microcomputed tomography (microCT). Cancellous bone volume fraction (BV/TV)
      decreased 60% between 6 weeks and 24 months of age. Loss was characterized by
      decreased trabecular number (Tb.N), increased trabecular spacing (Tb.Sp), and
      decreased connectivity. Anisotropy decreased while the structure model index
      increased with age. Cortical bone thickness increased between 6 weeks and 6
      months of age and then decreased continuously to 24 months (-12%). Cortical bone
      area (Ct.Ar) remained constant between 6 and 24 months. Fat-free weight reached a
      peak at 12 months and gradually declined to 24 months. Total mass lost between 12
      and 24 months reached 10%. Overall, the age-related changes in skeletal mass and
      architecture in the mouse were remarkably similar to those seen in human aging.
      Furthermore, the rapid early loss of cancellous bone suggests that bone loss is
      not just associated with old age in the mouse but rather occurs as a continuum
      from early growth. We conclude that the C57BL/6J male mouse maybe a useful model
      to study at least some aspects of age-related bone loss in humans.

PMID- 12054160
TI  - The incidence of vertebral fractures in men and women: the Rotterdam Study.
AB  - Vertebral fractures are considered the most common fractures in osteoporosis.
      Nevertheless, little is known about the epidemiology of these fractures,
      especially in men. Therefore, the incidence of vertebral fractures was studied in
      3469 men and women from the Rotterdam Study. Spinal radiographs were obtained at
      baseline and again after a mean follow-up of 6.3 years. The follow-up radiographs
      were scored for vertebral fractures using the McCloskey-Kanis assessment method.
      Whenever a vertebral fracture was detected, the radiograph was compared with the
      baseline radiograph. If this fracture was not already present at baseline, it was
      considered an incident fracture. The incidence increased strongly with age,
      ranging from 7.8/1,000 person years (PY) at ages 55-65 years to 19.6/1,000 PY at
      ages over 75 years for women, and 5.2-9.3/1,000 PY for men, respectively.
      Analyses repeated in strata of presence or absence of prevalent vertebral
      fractures showed that both in men and in women, the increase in incidence with
      age was almost exclusively observed in subjects with one or more prevalent
      fractures present at baseline. For both genders, the incidence of vertebral
      fractures doubled per SD decrease in lumbar spine or femoral neck bone mineral
      density (BMD). This study shows that overall, the incidence of vertebral
      fractures is higher in women-than in men. In both genders, the incidence
      increases with age. Furthermore, the presence of a prevalent vertebral fracture
      and a low BMD are strong independent predictors of incident vertebral fractures
      in men and women.

PMID- 12054161
TI  - Daily oral pamidronate in women and men with osteoporosis: a 3-year randomized
      placebo-controlled clinical trial with a 2-year open extension.
AB  - The efficacy and safety of oral pamidronate was examined in a double-blind,
      placebo-controlled trial in women and men with established osteoporosis. Seventy
      eight postmenopausal women and 23 men with at least one prevalent vertebral
      fracture were randomized separately to 150 mg/day of pamidronate or placebo for 3
      years followed by 150 mg/day of pamidronate for an additional 2 years. In
      addition, all patients received 400 U/day of cholecalciferol and 500 mg/day of
      elemental calcium. Pamidronate increased significantly bone mineral density of
      the lumbar spine (LS-BMD) and of the femoral neck (FN-BMD). The total increase in
      BMD of the spine after 5 years of treatment was 14.3%. Lateral spine radiographs
      were obtained at baseline and after 3 years of treatment. Fractures of previously
      normal vertebrae occurred in 15 of 45 patients treated with placebo (33.3%) and
      in 5 of 46 patients treated with pamidronate (11%). The relative risk was 0.33
      (95% CI, 0.14-0.77). Treatment was well tolerated and there was no difference in
      gastrointestinal toxicity between pamidronate and placebo-treated patients. One
      hundred fifty milligrams daily of pamidronate is an effective and safe treatment
      of women and men with established osteoporosis.

PMID- 12054162
TI  - Four-year gain in bone mineral in girls with and without past forearm fractures:
      a DXA study. Dual energy X-ray absorptiometry.
AB  - We have previously shown that girls with a recent distal forearm fracture have
      weaker skeletons than girls who have never fractured. This could be a transient
      or persistent phenomenon. The present study was undertaken to determine whether
      the bone mineral content (BMC) of girls with previous distal forearm fractures
      remains lower 4 years postfracture or if catch-up gain has occurred. We report
      baseline and follow-up dual energy X-ray absorptiometry (DXA) results for 163
      girls: 81 girls from the original control group who remained free of fracture
      (group 1) and 82 girls from the original group with distal forearm fractures
      (group 2). In data adjusted for bone area, height, weight, and pubertal status,
      group 2 girls had 3.5-8.5% less BMC at the total body, lumbar spine, ultradistal
      radius, and hip trochanter than group 1 at baseline, and 2.4-5.7% less BMC at
      these sites at follow-up. Even girls from group 2 who did not experience another
      fracture after baseline (n = 58) did not display greater BMC at follow-up
      compared with baseline values at any site, indicating that the decreased BMC at
      the time of fracture had persisted. In group 2, the relative gain in BMC after
      adjusting for the initial BMC and current bone area, height, weight, and pubertal
      stage was less than or similar to, but not greater than that of group 1 (ratio
      [95% CI]: total body, 0.985 [0.972-0.998]; lumbar spine, 0.961 [0.935-0.987];
      ultradistal radius, 0.968 [0.939-0.998]; hip trochanter, 0.955 [0.923-0.988];
      femoral neck, 0.981 [0.956-1.007]; and 33% radius 0.999 [0.977-1.021]). These
      findings indicate that girls with distal forearm fractures do not improve their
      gain of BMC. We conclude that girls who have sustained a distal forearm fracture
      maintain their lower BMC at most sites for at least 4 years.

PMID- 12054163
TI  - Male sex and low physical activity are associated with reduced spine bone mineral
      density in survivors of childhood acute lymphoblastic leukemia.
AB  - Survivors of acute lymphoblastic leukemia (ALL) are at risk of osteoporosis and
      obesity. We studied bone mineral density (BMD), percent of fat mass (%FM), and
      activity levels in survivors of ALL treated without radiotherapy. Lumbar and
      total areal BMD (g/cm2) and %FM were measured in 28 survivors (aged 5.7-14.7
      years) of childhood ALL by dual-energy X-ray absorptiometry (DXA) scan (GE Lunar,
      Prodigy) an average of 5 years after completion of chemotherapy (UK Medical
      Research Council randomized trial protocol XI [UKALL XI]). One boy fractured his
      arm during treatment. Apparent volumetric lumbar BMD (BMD(vol); g/cm3) was
      calculated and %FM was adjusted for sex and age (%FM(adj)). Physical activity was
      measured by accelerometer and questionnaire. The results were compared with 28
      sex- and age-matched healthy controls. Total body and lumbar areal BMD (g/cm2)
      were not different between the ALL group and the control group. However, mean
      lumbar BMD(vol) in survivors of ALL was significantly lower than in controls
      (0.303 +/- 0.036 g/cm3 vs. 0.323 +/- 0.03 g/cm3; p < 0.01), which mostly was
      caused by the difference in boys (0.287 +/- 0.032 g/cm3 vs. 0.312 +/- 0.027
      g/cm3; p < 0.05). Weekly activity score by questionnaire was significantly lower
      in the ALL group than in the control group (geometric mean 50 vs. geometric mean
      74; p < 0.05). Male gender, low activity levels and an intravenous (iv) high dose
      of methotrexate were associated with low lumbar BMD(vol). Patients who received
      an iv high dose of methotrexate (n = 18) had significantly higher %FM(adj) than
      those with intrathecal methotrexate only (n = 10; 141 +/- 70% vs. 98 +/- 37%;p <
      0.05). In conclusion, male survivors of childhood ALL have reduced lumbar
      BMD(vol), whereas no such difference was seen in girls. Overall, survivors of ALL
      were physically less active than their healthy controls and lower activity
      correlated with lower lumbar BMD(vol) and higher %FM(adj).

PMID- 12054164
TI  - The effects of growth hormone replacement therapy on bone metabolism in adult
      onset growth hormone deficiency: a 2-year open randomized controlled multicenter
      trial.
AB  - Adult hypopituitary patients with growth hormone deficiency (GHD) show a
      significant decrease in bone mass and an increased fracture rate. Replacement
      therapy with GH increases bone turnover. Most of the long-term data on bone
      mineral content (BMC) and bone mineral density (BMD) have been acquired in open,
      noncontrolled trials involving limited numbers of patients. To determine whether
      long-term GH therapy is beneficial for bone despite the increased bone turnover,
      100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with
      adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean
      dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women)
      for 24 months. Despite a similar increase in parameters of bone turnover
      (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and
      pyridinolines ([PYD]) in male and female GH-treated patients compared with
      controls, the effects on BMC and BMD as evaluated by dual-energy X-ray
      absorptiometry were gender specific. A significant increase in spine BMC and BMD
      and total hip BMD and a decrease in BMD at the ultradistal radius over time was
      observed in male GH-treated patients compared with the evolution in controls
      (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and
      p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008,
      respectively). No significant treatment effects were observed in female patients.
      Despite the increase in the total remodeling space induced by GH treatment,
      prolonged GH therapy in adult-onset GHD has a positive effect on bone balance,
      maintaining bone mass in women, and even increasing it in men over a 2 year
      period.

PMID- 12054165
TI  - Bone mineral content per muscle cross-sectional area as an index of the
      functional muscle-bone unit.
AB  - Bone densitometric data often are difficult to interpret in children and
      adolescents because of large inter- and intraindividual variations in bone size.
      Here, we propose a functional approach to bone densitometry that addresses two
      questions: Is bone strength normally adapted to the largest physiological loads,
      that is, muscle force? Is muscle force adequate for body size? To implement this
      approach, forearm muscle cross-sectional area (CSA) and bone mineral content
      (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19
      years of age (183 girls), using peripheral quantitative computed tomography
      (pQCT). Reference data were established for height-dependent muscle CSA and for
      the variation with age in the BMC/muscle CSA ratio. These reference data were
      used to evaluate results from three pediatric patient groups: children who had
      sustained multiple fractures without adequate trauma (n = 11), children with
      preterminal chronic renal failure (n = 11), and renal transplant recipients (n =
      15). In all three groups mean height, muscle CSA, and BMC were low for age, but
      muscle CSA was normal for height. In the multiple fracture group and in renal
      transplant recipients the BMC/muscle CSA ratio was decreased (p <. 0.05),
      suggesting that bone strength was not adapted adequately to muscle force. In
      contrast, chronic renal failure patients had a normal BMC/muscle CSA ratio,
      suggesting that their musculoskeletal system was adapted normally to their
      (decreased) body size. This functional approach to pediatric bone densitometric
      data should be adaptable to a variety of densitometric techniques.

PMID- 12054166
TI  - Tumors associated with oncogenic osteomalacia express genes important in bone and
      mineral metabolism.
AB  - Oncogenic osteomalacia (OOM) is associated with primitive mesenchymal tumors that
      secrete phosphaturic factors resulting in low serum concentrations of phosphate
      and calcitriol, phosphaturia, and defective bone mineralization. To identify
      overexpressed genes in these tumors, we compared gene expression profiles of
      tumors resected from patients with OOM and histologically similar control tumors
      using serial analysis of gene expression (SAGE). Three hundred and sixty-four
      genes were expressed at least twofold greater in OOM tumors compared with control
      tumors. A subset of 67 highly expressed genes underwent validation with an
      extended set of OOM and control tumors using array analysis or reverse
      transcription polymerase chain reaction (RT-PCR). Ten of these validated genes
      were consistently overexpressed in all OOM tumors relative to control tumors.
      Strikingly, genes with roles in bone matrix formation, mineral ion transport, and
      bone mineralization were highly expressed in the OOM tumors.

PMID- 12054167
TI  - Localization of the gene causing autosomal dominant osteopetrosis type I to
      chromosome 11q12-13.
AB  - The osteopetroses are a heterogeneous group of genetic conditions characterized
      by increased bone density due to impaired bone resorption by osteoclasts. Within
      the autosomal dominant form of osteopetrosis, the radiological type I (ADOI) is
      characterized by a generalized osteosclerosis, most pronounced at the cranial
      vault. The patients are often asymptomatic but some suffer from pain and hearing
      loss. ADOI is the only type of osteopetrosis not associated with an increased
      fracture rate. Linkage analysis in two families with ADOI from Danish origin
      enabled us to assign the disease-causing gene to chromosome 11q12-13. A summated
      maximum lod score of +6.54 was obtained with marker D11S1889 and key recombinants
      allowed delineation of a candidate region of 6.6 cM between markers D11S1765 and
      D11S4113. Previously, genes causing other conditions with abnormal bone density
      have been identified from this chromosomal region. The TCIRG1 gene was shown to
      underly autosomal recessive osteopetrosis (ARO), and, recently, mutations in the
      LRP5 gene were found both in the osteoporosis-pseudoglioma syndrome and the high
      bone mass trait. Because both genes map within the candidate region for ADOI, it
      can not be excluded that ADOI is caused by mutations in either the TCIRG1 or the
      LRP5 gene.

PMID- 12054168
TI  - Mineralization of developing mouse calvaria as revealed by Raman
      microspectroscopy.
AB  - Raman microspectroscopy is a nondestructive vibrational spectroscopic technique
      that permits the study of organic and mineral species at micron resolution,
      offers the ability to work with hydrated and dehydrated specimens in vivo or in
      vitro, and requires minimal specimen preparation. We used Raman microspectroscopy
      to determine the composition of the mineral environments present in mouse
      calvaria, the flat bones that comprise the top of the skull. We have acquired
      Raman transects (lines of point spectra) from mouse calvaria during a
      developmental time course ranging from embryonic day 13.5 (E13.5; 6 days before
      birth) to 6 months of age. Exploratory factor analysis (FA) reveals the presence
      of a variety of apatitic mineral environments throughout the tissue series. The
      earliest mineral is observed in the fetal day 15.5 (F15.5) mice and is identified
      as a carbonated apatite. The presence of a heterogeneous mineralized tissue in
      the postnatal specimens suggests that ionic incorporation and crystal perfection
      in the lattice yary as the mouse develops. This variation is indicative of the
      presence of both recently deposited mineral and more matured remodeled mineral.
      Band area ratios reveal that the mineral/matrix ratio initially increases,
      reaches a plateau, and then increases again. The carbonate/phosphate band area
      ratio remains constant from F18.5 to postnatal day 3 (PN3) and then increases
      with age. Insights into the chemical species, the degree of mineralization, and
      the multiple mineral environments that are present in normal calvarial tissue
      will enable us to better understand both normal and abnormal mineralization
      processes.

PMID- 12054169
TI  - Paget's disease in an archeological population.
AB  - The aim of this investigation was to study the prevalence and distribution of
      Paget's disease in an archeological population. Paget's disease, first described
      over 100 years ago, is a well-recognized chronic disorder involving abnormal bone
      turnover with established radiological features. Prevalence within modern
      populations varies both within individual countries and between them.
      Paleopathological examples are uncommon and sporadically reported both from
      Europe and the Americas and from many periods of history. A large skeletal
      assemblage (2,770 individuals) from Barton on Humber, UK, provided an opportunity
      to examine the prevalence of Paget's disease in one area of the northern England
      over the period 900-1,850 AD. All bones were examined visually for evidence of
      Paget's disease of the bone (PDB) and all abnormal bones were examined further by
      plain radiography. Fifteen cases of probable Paget's disease were found. The
      overall prevalence was 2.1% in those aged >40 years. The prevalence before 1500
      AD was 1.7% and post-1500 AD was 3.1%. The distribution of disease mirrored
      modern disease, with the lumbar spine, pelvis, and proximal femur being the
      commonest sites. The prevalence of Paget's disease in the United Kingdom over the
      last 1,000 years has been assessed. Although there is a trend of increasing
      prevalence, this did not reach statistical significance. This is likely caused by
      the small sample size, but this is by far the greatest number of cases of PDB
      described in a single skeletal assemblage to date. The distribution of lesions
      within the skeleton is unchanged.

PMID- 12054170
TI  - Leptin receptor (OB-R) gene expression in human primary osteoblasts:
      confirmation.

PMID- 12054171
TI  - Cyclo-oxygenase 2 function is essential for bone fracture healing.
AB  - Despite the molecular and histological similarities between fetal bone
      development and fracture healing, inflammation is an early phase of fracture
      healing that does not occur during development. Cyclo-oxygenase 2 (COX-2) is
      induced at inflammation sites and produces proinflammatory prostaglandins. To
      determine if COX-2 functions in fracture healing, rats were treated with COX-2
      selective nonsteroidal anti-inflammatory drugs (NSAIDs) to stop COX-2-dependent
      prostaglandin production. Radiographic, histological, and mechanical testing
      determined that fracture healing failed in rats treated with COX-2-selective
      NSAIDs (celecoxib and rofecoxib). Normal fracture healing also failed in mice
      homozygous for a null mutation in the COX-2 gene. This shows that COX-2 activity
      is necessary for normal fracture healing and confirms that the effects of COX-2
      selective NSAIDs on fracture healing is caused by inhibition of COX-2 activity
      and not from a drug side effect. Histological observations suggest that COX-2 is
      required for normal endochondral ossification during fracture healing. Because
      mice lacking Cox2 form normal skeletons, our observations indicate that fetal
      bone development and fracture healing are different and that COX-2 function is
      specifically essential for fracture healing.

PMID- 12054172
TI  - Do inhibitors of cyclooxygenase-2 impair bone healing?

PMID- 12054173
TI  - Osteoblastic 11beta-hydroxysteroid dehydrogenase type 1 activity increases with
      age and glucocorticoid exposure.
AB  - The risk of glucocorticoid-induced osteoporosis increases substantially with age
      but there is considerable individual variation. In recent studies we have shown
      that the effects of glucocorticoids on bone are dependent on autocrine actions of
      the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1); expression
      of 11beta-HSD1 in osteoblasts (OBs) facilitates local synthesis of active
      glucocorticoids with consequent effects on osteoblastic proliferation and
      differentiation. Using primary cultures of human OBs, we have now characterized
      the age-specific variation in osteoblastic 11beta-HSD1 and defined enzyme
      kinetics and regulation using natural and therapeutic glucocorticoids. 11beta
      HSD1 reductase activity (cortisone to cortisol conversion) was recognized in all
      OB cultures and correlated positively with age (r = 0.58 with all cultures, p <
      0.01, and n = 18; r = 0.87 with calcaneal-derived cultures, p < 0.001, and n =
      14). Glucocorticoid treatment caused a time- and dose-dependent increase in
      11beta-HSD1 activity over control (e.g., dexamethasone [DEX; 1 microM], 2.6-fold
      +/- 0.5 (mean +/- SE), p < 0.001, and n = 16; cortisol (100 nM), 1.7-fold +/-
      0.1, p < 0.05, and n = 14). Similar increases in 11beta-HSD1 mRNA expression were
      indicated using real-time quantitative reverse-transcription polymerase chain
      reaction (RT-PCR) analyses (3.5-fold with DEX, p < 0.01; 2.5-fold with cortisol,
      p < 0.05). The capacity of 11beta-HSD1 to metabolize the synthetic
      glucocorticoids prednisone and prednisolone was investigated in human OBs (hOBs)
      and fetal kidney-293 cells stably transfected with human 11beta-HSD1 cDNA.
      Transfected cells and hOBs were able to interconvert prednisone and prednisolone
      with reaction kinetics indistinguishable from those for cortisone and cortisol.
      To assess the in vivo availability of substrates for osteoblastic 11beta-HSD1,
      plasma cortisone and prednisone levels were measured in normal males before and
      after oral prednisolone (5 mg). The 9:00 a.m. serum cortisone levels were 110 +/-
      5 nmol/liter and prednisone levels peaked at 78 +/- 23 nmol/liter 120 minutes
      after administration of prednisolone. Thus, therapeutic use of steroids increases
      substrate availability for 11beta-HSD1 in bone. These studies indicate that
      activation of glucocorticoids at an autocrine level within bone is likely to play
      an important role in the age-related decrease in bone formation and increased
      risk of glucocorticoid-induced osteoporosis.

PMID- 12054174
TI  - 11beta-hydroxysteroid dehydrogenase, an amplifier of glucocorticoid action in
      osteoblasts.

PMID- 12054175
TI  - Tumor necrosis factor modulates apoptosis of monocytes in areas of
      developmentally regulated bone remodeling.
AB  - Tooth eruption is characterized by spatially segregated bone resorption along the
      path of eruption and bone formation in the opposite direction. Monocyte
      recruitment occurs in two distinct peaks in both areas of resorption and
      formation. Without such recruitment tooth eruption does not occur. The signals
      that regulate this recruitment are thought to involve the expression of cytokines
      and chemokines. One such cytokine is tumor necrosis factor (TNF), which can
      affect monocyte recruitment through the induction of chemokines and adhesion
      molecules and increase their lifespan by acting as antiapoptotic cell survival
      signals. We examined the latter by studying mice with targeted deletions of TNF
      receptors p55 and p75 (TNFRp55/p75). The results indicate that mice that lack
      functional TNF receptors have a significantly reduced number of monocytes in the
      apical area associated with bone formation. The reduced number of monocytes in
      this area can be accounted for by an increase in apoptosis in TNFRp55-/-/p75-/-.
      In contrast, the number of monocytes, the rate of monocyte apoptosis, and the
      formation of osteoclasts in the occlusal area associated with bone resorption
      occurred independently of TNF activity. These results suggest that TNF receptor
      signaling can affect tooth eruption by acting as a monocyte survival signal in
      some but not all areas of bone undergoing developmentally regulated remodeling.

PMID- 12054176
TI  - Dissociation of angiogenesis and osteoclastogenesis during endochondral bone
      formation in neonatal mice.
AB  - Invasion of the mineralized matrix by endothelial cells and osteoclasts is a key
      event in endochondral bone formation. To examine the putative role of osteoclast
      activity in the angiogenic process, we used two in vivo models of suppressed bone
      resorption: mice treated with the bisphosphonate clodronate and in osteoclast
      deficient, osteopetrotic mice. Angiogenesis was assessed in caudal vertebrae of
      these neonatal mice. This model enables us to study the interaction between
      osteoclasts and endothelial cells during endochondral bone formation. In control
      conditions, sinusoid-like structures were detected in the vicinity of tartrate
      resistance acid phosphatase positive (TRAcP+) osteoclasts. Treatment with
      clodronate completely abolished osteoclastic bone resorption, whereas
      angiogenesis remained unaffected. In line with these observations, in the
      osteopetrotic mouse mutants c-fos knockout mice and op/op mice, capillaries
      invaded the calcified cartilage in the absence of osteoclasts. In conclusion, our
      data strongly suggest that during endochondral bone formation, vascular invasion
      can occur in the absence of osteo(chondro)clastic resorption. In addition,
      bisphosphonates show no apparent effect on angiogenesis in this in vivo model.
      These findings may have important clinical implications in the management of
      skeletal disorders such as metastatic bone disease, in which both osteoclastic
      bone resorption and angiogenesis contribute to tumor growth. On the other hand,
      our results confirm that bisphosphonates can be used safely in the treatment of
      disorders that affect the growing skeleton, such as in juvenile osteoporosis.

PMID- 12054178
TI  - TVT: on midurethral tape positioning and its influence on continence.
AB  - All known original and subsequent publications describing the treatment of stress
      urinary incontinence by means of tension-free vaginal tape (TVT) assert that
      fixing the tape in a midurethral position is an absolute requirement for
      restoring continence and avoiding bladder voiding disorders. These studies assume
      that TVT works by replacing defective pubourethral ligaments inserting at the
      midurethra. In 20 patients we intraoperatively marked the suburethral position of
      the tape by metal clips and X-ray-proof string, and documented this
      postoperatively by X-ray images. In most cases the tape was located in the
      proximal third of the urethra, which did not cause a higher rate of bladder
      voiding disorders. All 20 patients became continent through the operation. We do
      not contest the efficiency of the TVT procedure, but we disprove first, that
      correctly performed operations always result in the midurethral location of the
      tape, and secondly that the midurethral position is decisive for its success.

PMID- 12054177
TI  - Vaginal erosion of cadaveric fascia lata following abdominal sacrocolpopexy and
      suburethral sling urethropexy.
AB  - The aim of this paper is to report vaginal erosion of cadaveric fascia lata used
      for abdominal sacrocolpopexy and suburethral sling urethropexy. The charts of
      patients who underwent abdominal sacrocolpopexy or suburethral sling urethropexy
      between March 1994 and February 1999 were reviewed for perioperative data. In 47
      cases of abdominal sacrocolpopexy or suburethral sling, 32 utilized cadaveric
      fascia lata, with 11 for sacrocolpopexy and 22 for suburethral sling. Vaginal
      erosion of cadaveric fascia lata graft was noted in 5 (23%) following sling
      procedure and 3 (27%) following sacrocolpopexy, diagnosed a mean of 36.8 days (+/
      7.1, range 27-45) following surgery. These women were treated conservatively
      with estrogen vaginal cream, and both vaginal and oral antibiotics. Four of the 8
      (50%) underwent excision of the exposed graft and reapproximation of the vaginal
      edges under local anesthesia, whereas the remainder responded to medical therapy
      alone. None of the patients experienced recurrence of vaginal vault prolapse or
      urinary incontinence following graft erosion. Comparison of women with vaginal
      erosion of cadaveric fascia lata to those without revealed an association with
      perioperative febrile morbidity (P=0.04), but not with age, hormonal or insurance
      status, body mass index, history of diabetes mellitus or smoking, length of
      surgery, estimated blood loss, change in hematocrit, or other perioperative
      complications. Vaginal erosion of cadaveric fascia lata utilized for abdominal
      sacrocolpopexy and suburethral sling was noted in 25% of our patients and may
      have an infectious etiology. Conservative treatment with antibiotics and estrogen
      is effective, but removal of exposed graft with vaginal closure may be necessary.

PMID- 12054179
TI  - The histomorphologic structure of the levator ani muscle and its functional
      significance.
AB  - The levator ani muscle (LAM), unlike other striated muscles has resting
      myoelectric activity, the cause of which is not precisely known. In a recent
      study this activity was suggested to be related to the presence of smooth muscle
      bundles in the LAM. The present study investigated this point in 25 cadaveric
      specimens (10 neonates, 15 adults). Histologic examination of the LAM was
      performed in 12 specimens, three to six slices being taken from the lateral to
      the medial side of each muscle, processed and stained with H&E and Masson's
      trichrome stain. The remaining 13 specimens were studied by direct dissection and
      photographed. Microscopic examination of specimens from adult cadavers showed
      that the lateral part of the LAM consisted of purely skeletal muscle bundles,
      mostly of the small-caliber type and few of the large or intermediate type. As we
      proceeded medially, smooth muscle bundles started to appear. Examination of
      slices medial to the midportion of the LAM showed that the muscle began to be
      separated into two layers: a deep (pelvic) one formed of smooth fibers and a
      superficial (perineal) one of skeletal fibers, separated by a neurovascular
      plane. Microscopic examination of specimens from neonates showed that the whole
      LAM consisted of skeletal fibers; no smooth fibers or separation into two layers
      were identified. By direct dissection of the adult specimens the medial part of
      the LAM consisted of two layers, superficial and deep, which were separated by
      fascia containing vessels and nerves. The muscle was thicker at its medial part
      and tapered laterally, with loss of demarcation, into two layers. Specimens from
      neonates showed no differentiation of the LAM, into two layers. It is suggested
      that the deep layer of the LAM, which was formed of smooth fibers, acts
      involuntarily, supporting the pelvic viscera by its tone and responding to
      variations in intra-abdominal pressure by adaptation of this tone. The
      superficial layer of the LAM, made of skeletal fibers, appears to represent the
      functional mobile part that acts voluntarily during urination or defecation. The
      presence of the smooth fibers in the adult LAM and not in neonates seems to be
      adaptational, caused by the action of intra.abdominal pressure and visceral
      weight. The skeletal fibers pass into various histologic stages before they
      transform to smooth fibers.

PMID- 12054180
TI  - Pelvic floor and abdominal muscle interaction: EMG activity and intra-abdominal
      pressure.
AB  - Pelvic floor muscle exercises prescribed for the treatment of incontinence
      commonly emphasize concurrent relaxation of the abdominal muscles. The purpose of
      this study was to investigate the interaction between individual muscles of the
      abdominal wall and the pelvic floor using surface and intramuscular
      electromyography, and the effect of their action on intra-abdominal pressure.
      Four subjects were tested in the supine and standing positions. The results
      indicated that the transversus abdominis (TA) and the obliquus internus (OI) were
      recruited during all pelvic floor muscle contractions. It was not possible for
      these subjects to contract the pelvic floor effectively while maintaining
      relaxation of the deep abdominal muscles. A mean intra-abdominal pressure rise of
      10 mmHg (supine) was recorded during a maximum pelvic floor muscle contraction.
      These results suggest that advice to keep the abdominal wall relaxed when
      performing pelvic floor exercises is inappropriate and may adversely affect the
      performance of such exercises.

PMID- 12054182
TI  - Ilioinguinal nerve entrapment after tension-free vaginal tape (TVT) procedure.
AB  - The anatomy of the ilioinguinal nerve makes it vulnerable to entrapment near its
      exit from the superficial inguinal ring, where it lies almost directly superior
      to the pubic tubercle. Ilioinguinal nerve entrapment is a documented complication
      of inguinal herniorrhaphy, inguinal lymph node dissection, appendectomy,
      Pfannenstiel incision and the needle suspension procedure. It has not previously
      been described as a complication of the tension-free vaginal tape (TVT)
      procedure, which is the most recent technique for the treatment of genuine
      urinary stress incontinence. This paper describes a clinical history to
      illustrate the diagnosis and management of ilioinguinal nerve entrapment
      occurring as a complication of tension-free vaginal tape procedure.

PMID- 12054181
TI  - Repeat tension-free transvaginal tape (TVT) sling for the treatment of recurrent
      stress urinary incontinence.
AB  - The pubovaginal sling is one of the preferred procedures for the treatment of
      female stress urinary incontinence because of its improved long-term cure rates.
      Recently a modified technique of the pubovaginal sling, known as the tension-free
      transvaginal tape (TVT), has gained popularity. We present the first reported
      cases of repeat TVT pubovaginal sling for the treatment of patients with
      recurrent stress urinary incontinence. Both patients had repeat TVT slings
      performed between 6 and 9 months following the initial procedure without revision
      or removal of the previous TVT sling. Both patients reported surgical cure
      without significant intraoperative or postoperative complications. It appears
      that reapplication of the TVT polypropolene sling may be a viable option in the
      event of initial TVT sling failure.

PMID- 12054183
TI  - Neurovesical dysfunction in postural tachycardia syndrome (POTS).
AB  - This is the first report of neurovesical dysfunction in a woman with postural
      tachycardia syndrome (POTS). The patient had both symptoms and urodynamic
      findings diagnostic of detrusor hyperreflexia. Management consisted of
      anticholinergic medication and timed voiding. Lower urinary tract dysfunction may
      be underrecognized in POTS.

PMID- 12054184
TI  - Dumbing down.

PMID- 12054185
TI  - Repeatability of cystometry and pressure-flow parameters in female patients.
AB  - The repeatability of cystometric and pressure-flow data was studied in 31 female
      patients. The measured parameters had poor correlation coefficients, and
      logarithmic transforming of the data was generally not warranted. Previous
      studies and statistical methods of reliability measurement are reviewed. It is
      suggested as a subject for future studies, that urodynamic measurements are
      repeated in each patient so that confidence limits can be established within
      disease entities.

PMID- 12054186
TI  - Biomechanical properties of prolapsed vaginal tissue in pre- and postmenopausal
      women.
AB  - The aim of this study was to biomechanically assess vaginal tissue from pre- and
      postmenopausal women with symptomatic prolapse. Vaginal tissue was collected at
      the time of surgery in women with symptomatic prolapse. Tissue specimens were
      biomechanically assessed by a purpose-built tissue puller system and stress
      strain curves were digitally recorded. Tissue was stretched at a constant rate of
      0.8 mm/s to an elongation of 8 mm. A force-stiffness relationship was obtained.
      All data were normalized for length and cross-sectional area of the specimens.
      Tissues from the anterior vaginal wall were analyzed in 10 postmenopausal and 8
      premenopausal women. The mean age of the postmenopausal women was 69 years,
      compared to 41 years for premenopausal women. Pre- and postmenopausal groups show
      very little or no difference regarding elongation or long-term tissue
      deformation. A significantly higher elastic modulus was observed in
      postmenopausal vaginal tissue. This is most likely an age-related phenomenon.
      Apart from this, pre- and postmenopausal vaginal tissue showed few differences in
      biomechanical assessment.

PMID- 12054187
TI  - Collagen metabolism and turnover in women with stress urinary incontinence and
      pelvic prolapse.
AB  - The aim of this study was to investigate quantitative mRNA expression of matrix
      metalloproteinases MMP-1, MMP-2, MMP-9, and their inhibitors, the tissue
      inhibitors of metalloproteinases TIMP-1, TIMP-2 and TIMP-3, in vaginal wall
      tissue from women with stress urinary incontinence compared to continent
      controls. Vaginal wall tissues were obtained from 7 women with stress urinary
      incontinence/severe pelvic prolapse and 15 continent controls. RNA was then
      extracted and quantified. Quantitative competitive reverse transcription (QC-RT
      PCR) was carried out with oligonucleotide primers to quantify MMP-1, MMP-2, MMP
      9, TIMP-1, TIMP-2 and TIMP-3 mRNA expression. Stress continent women demonstrated
      a significant decrease in TIMP-1 and mRNA expression (P = 0.03). There was no
      difference in TIMP-2, TIMP-3, MMP-2 or MMP-9 mRNA expression between stress
      incontinent women and controls. However, MMP-1 mRNA expression was significantly
      increased (P = 0.05) in the incontinent group and the MMP-1/TIMP-1 ratio (P =
      0.04) was consistent with increased collagen degradation in the stress
      incontinence. Stress incontinent women demonstrated an increase in MMP-1 mRNA
      expression and a decrease in the inhibitor TIMP-1 mRNA expression. Both these
      findings are consistent with increased collagen breakdown as a pathologic
      etiology of incontinence.

PMID- 12054188
TI  - Long-term results of the FemSoft urethral insert for the management of female
      stress urinary incontinence.
AB  - A 5-year ongoing, controlled multicenter study enrolled 150 women. Outcome
      measures included pad weight tests (PWT), voiding diary (VD), quality of life
      (QOL) and satisfaction questionnaires. Outcome measures during the baseline
      period were compared to evaluations during follow-up. Concurrent evaluations with
      and without device use were also performed. Safety evaluations included
      urinalysis and culture, leak-point pressure (LPP) and cystoscopy. Adverse events
      (AE) were recorded throughout the study. One to 2 years of follow-up were
      collected on all study participants (mean 15 months). Statistically significant
      reductions in overall daily incontinence episodes (P<0.001) and PWT urine loss
      (P<0.001) were observed with the device at all follow-up intervals, and 93% of
      women had a negative PWT at 12 months. Women were satisfied with ease of use of
      the device, comfort and dryness, and significant improvements in QOL were
      observed (P<0.001). Subgroup analysis revealed that the insert was effective,
      despite the presence of urgency, low LPP, failed surgery and advanced age. AE
      included symptomatic urinary tract infection in 31.3%, mild trauma with insertion
      in 6.7%, hematuria in 3.3%, and migration in 1.3% of women. The results of PWT
      and VD demonstrated device efficacy. Women were satisfied and significant
      improvements in QOL were observed. AE were transient and required minimal or no
      treatment. The urethral insert should be considered as an option for the
      management of SUI.

PMID- 12054189
TI  - Important clinical outcomes in urogynecology: views of patients, nurses and
      medical staff.
AB  - We attempted to grade treatment outcomes in female urinary incontinence by the
      perceived importance of these outcomes for patients, nursing staff and medical
      staff. One hundred millimeter visual analog scales (VAS) quantifying the relative
      importance of five clinical outcomes were sent to 100 patients, 50 nursing staff
      and 135 medical staff involved in continence care and median VAS scores for each
      outcome were compared between groups. Subjective improvement and improvement in
      quality of life were rated most highly. Median scores for subjective cure were 93
      (76-99) for nurses, 93 (11-100) for patients and 91 (50-100) for ICS (UK)
      members. Median quality of life improvement scores were 92 (67-100), 93 (3-100)
      and 93 (74-100), respectively (not significant). There was a striking concordance
      of opinion regarding the importance of subjective improvement and improvement in
      quality of life. We suggest that these should become primary outcome measures in
      all future clinical trials and audits of incontinence treatments.

PMID- 12054190
TI  - Grades of intrinsic sphincteric deficiency (ISD) associated with female stress
      urinary incontinence.
AB  - Intrinsic urethral sphincter deficiency (ISD) is a clinical entity that should be
      suspected in women with stress urinary incontinence. If it is not diagnosed prior
      to surgery, it poses a significant risk factor for repair failure. We propose a
      classification of ISD based on videofluorourodynamic (VFUD) and abdominal leak
      point pressures. One hundred female patients with stress urinary incontinence due
      to ISD were included in this study. History and physical examination were
      performed on all patients. Each patient underwent a standard VFUD study with
      abdominal leak-point pressure (ALPP) measurement. ISD is classified into subtypes
      according to VFUDS and ALPP. The findings were then correlated with the clinical
      presentation, etiology and proposed management. Three types of ISD/SUI were
      identified. ISD-A, subtle/urodynamic, was present in 32 patients (32%). It is
      most difficult to diagnose because radiologically the bladder neck is not open at
      rest, and it is only diagnosed by VFUD. The abdominal leak-point pressure was
      less than 12 cmH2O. ISD-B was present in 45 patients (45%). This is characterized
      by a beak-shaped open bladder neck at rest. The abdominal leak-point pressure was
      less than 90 cmH2O. ISD-C was present in 14 patients (14%). It is characterized
      by an open, fixed non-functioning urethra (pipe-stem) with high position of the
      bladder neck. The abdominal leak-point pressure was less than 70 cmH2O. All the
      three subtypes had proximal urethral closure pressure (PCUP) less than 10 cmH2O.
      Based on these data, the treatment options may vary from one subtype to another.
      For ISD-A, initial treatment was medical, with collagen injection being used for
      the failed cases. For ISD-B a modified pubovaginal sling was used, as it corrects
      the ISD and the urethral hypermobility at the same time. For ISD-C, urethrolysis
      and takedown of the previous suspension was required before using a sling.
      Collagen injections were used in selected cases. This classification identifies
      different subgroups of ISD, which is important in the diagnosis and management of
      this condition.

PMID- 12054191
TI  - Robust circadian rhythmicity of Per1 and Per2 mutant mice in constant light, and
      dynamics of Per1 and Per2 gene expression under long and short photoperiods.
AB  - The Per1 and Per2 genes are components of the mammalian circadian clock.
      Mutations in these genes alter phase resetting in response to a nocturnal light
      pulse, and Per2 mutant mice are known to become arrhythmic in constant darkness.
      We show that under constant light conditions, Per2 mutant mice exhibit robust
      activity rhythms as well as body temperature rhythms with a period length that is
      less than 24 h. In Per1 mutants, the period length of both activity and body
      temperature rhythms is longer than 24 h in constant light. Per1 mutants prolong
      their period length (tao) when illuminance is increased, whereas Per2 mutants
      shorten their endogenous period. Additionally, the authors show that the
      circadian pattern of Per1 and Per2 gene expression in mice is modified under
      different photoperiods and that there is a mutual influence of these genes on
      their timing of expression. We propose that, in mice, the phase relationship
      between Per1 and Per2 gene expression might be critical for transducing day
      length information to the organism. Per1 could be part of a morning oscillator
      tracking dawn, and Per2 could be part of an evening oscillator tracking dusk.

PMID- 12054192
TI  - Enhanced longevity in tau mutant Syrian hamsters, Mesocricetus auratus.
AB  - The single-gene mutation tau in the Syrian hamster shortens the circadian period
      by about 20% in the homozygous mutant and simultaneously increases the mass
      specific metabolic rate by about 20%. Both effects might be expected to lead to a
      change in longevity. To test such expectations, the life span of male and female
      hamsters from three genotypes (wild-type, heterozygous, and homozygous tau
      mutants, all derived from heterozygote crosses to randomize the genetic
      background) was recorded in constant darkness. Male hamsters lived significantly
      longer than females: the overall average life span was 96.9 weeks (SE = 2.5, n =
      118) for males and 82.0 weeks (SE = 2.1, n = 99) for females. To our surprise,
      male and female homozygous mutant hamsters lived significantly longer rather than
      shorter compared to wild-types. For males, the difference between the two
      genotypes was on average 14%; for females, the difference was 16%. The mortality
      rate of wild-type males was significantly different from that of homozygous tau
      males but not different from that of heterozygotes. Overall, survival of wild
      type females was statistically distinguishable from both heterozygous and
      homozygous mutant females. Male and female wild-type hamsters were heavier than
      homozygote mutants throughout the entire life span, and heterozygous mutants had
      intermediate weights. There was no correlation between body mass and life span,
      and the causes of the extended life span in tau mutant hamsters remain
      unresolved.

PMID- 12054193
TI  - The intergeniculate leaflet, but not the visual midbrain, mediates hamster
      circadian rhythm response to constant light.
AB  - Several studies have demonstrated a variety of effects of intergeniculate leaflet
      (IGL) lesions on circadian rhythm regulation. Recent studies have suggested the
      possibility that certain rhythm functions attributed to the IGL are actually
      controlled by retinorecipient midbrain nuclei or other brain areas connected to
      the IGL. The present investigations evaluated whether midbrain lesions previously
      shown to block the phasic actions of benzodiazepine would also reduce or
      eliminate the period-lengthening effect of constant light (LL), a function that
      has been attributed to the IGL. Experiment 1 established that the circadian
      period of controls lengthened by about 0.57 h when the animals were transferred
      from constant dark (DD) to LL, but the magnitude of change was attenuated by
      about 50% in animals with IGL lesions caused by the neurotoxin N-methyl-D
      aspartate (NMDA). In experiment 2, controls were compared to groups receiving
      either NMDA lesions of the pretectum or tectum or knife cuts designed to sever
      connections between the IGL and more medial retinorecipient nuclei. As in
      experiment 1, there were no differences between groups with respect to circadian
      period in DD. However, unlike experiment 1, all groups lengthened period equally
      in LL (overall mean increase = 0.57 h). Thus, the effect of LL on circadian
      period appears to be a joint result of photic information arriving at the
      circadian clock directly from the retinohypothalamic tract and indirectly through
      the IGL via the geniculohypothalamic tract, without involvement of visual
      midbrain. The results may have implications for the anatomical basis of Aschoff's
      rule.

PMID- 12054194
TI  - Circadian clock resetting by sleep deprivation without exercise in Syrian
      hamsters: dark pulses revisited.
AB  - Circadian rhythms in Syrian hamsters can be phase shifted by procedures that
      stimulate wheel running ("exercise") in the mid-subjective day (the hamster's
      usual sleep period). The authors recently demonstrated that keeping hamsters
      awake by gentle handling, without continuous running, is sufficient to mimic this
      effect. Here, the authors assessed whether wakefulness, independent of wheel
      running, also mediates phase shifts to dark pulses during the midsubjective day
      in hamsters free-running in constant light (LL). With running wheels locked
      during a 3 h dark pulse on day 3 of LL, hamsters (N = 16) averaged only 43+/-15
      min of spontaneous wake time and phase shifted only 24+/-43 min. When wheels were
      open during a dark pulse, two hamsters remained awake, ran continuously, and
      showed phase advance shifts of 7.3 h and 8.7 h, respectively, whereas the other
      hamsters were awake <60 min and shifted only 45+/-38 min. No animals stayed awake
      for 3 h without running. Additional time in LL (10 and 20 days) did not
      potentiate the waking or phase shift response to dark pulses. When all hamsters
      were sleep deprived with wheels locked during a dark pulse, phase advance shifts
      averaged 261+/-110 min and ranged up to 7.3 h. These shifts are large compared to
      those previously observed in response to the 3 h sleep deprivation procedure.
      Additional tests revealed that this potentiated shift response is dependent on LL
      prior to sleep deprivation but not LL after sleep deprivation. A final sleep
      deprivation test showed that a small part of the potentiation may be due to
      suppression of spontaneous wheel running by LL. These results indicate that some
      correlate of waking, other than continuous running, mediates the phase-shifting
      effect of dark pulses in the mid-subjective day. The mechanism by which LL
      potentiates shifting remains to be determined. The lack of effect of subsequent
      LL on the magnitude of shifts to sleep deprivation in the dark suggests that LL
      reduces responsivity to light by processes that take >3 h of dark to reverse.

PMID- 12054195
TI  - Phase shifting the hamster circadian clock by 15-minute dark pulses.
AB  - The mammalian circadian pacemaker can be phase shifted by exposure to a period of
      darkness interrupting otherwise continuous light. Circadian phase shifting by
      dark pulses was interpreted originally as reflecting a photic mirror-image
      mechanism, but more recent observations suggest that dark pulse-induced phase
      shifting may be mediated by a nonphotic, behavioral state-dependent mechanism.
      The authors recently presented evidence indicating that the dark-pulse phase
      response curve (PRC) is in fact a complex function, reflecting both photic mirror
      image and nonphotic mechanisms at different phases of the circadian cycle.
      Previous studies of dark pulse-induced phase shifting have universally employed
      relatively long (2 to 6 h) pulses, which complicates PRC analysis due to the
      extended segment of the underlying PRC spanned by such a long pulse. The present
      study was therefore designed to examine the phase-shifting effects of brief 15
      min dark pulses presented at both mid-subjective day and subjective dusk, and to
      explore the possible activity dependence of these effects by using physical
      restraint to prevent evoked locomotor activity. The results indicate that 15-min
      dark pulses are effective phase-shifting stimuli at both midday and dusk.
      Furthermore, as with longer dark pulses, phase shifting by 15-min dark pulses is
      completely blocked by physical restraint during subjective day but combines in a
      simple additive manner with the independent phase-shifting effect of restraint at
      subjective dusk.

PMID- 12054196
TI  - Djungarian hamsters: a species with a labile circadian pacemaker? Arrhythmicity
      under a light-dark cycle induced by short light pulses.
AB  - In most cases, phase-shifting effects of light pulses are studied in animals kept
      in constant darkness (DD) or in animals released into DD following the stimulus.
      In this study, the authors exposed Djungarian hamsters (Phodopus sungorus) to
      short light pulses during the dark phase of a 16:8 light-dark (LD) cycle and thus
      obtained a type VI phase response curve. Light pulses early in the night caused
      phase delays of the activity onset as well as phase advances of the activity
      offset, whereas light pulses later in the night resulted in phase advances of the
      activity offset only. A combination of two 15-min light pulses-the first one
      given late in the scotophase and the second given early in the dark phase of the
      following night-led to a strong compression of the activity phase alpha. In 75%
      of all animals, daily rhythms were no longer visible after complete alpha
      compression, and long-term arrhythmicity (up to 145 days) persisted despite
      continued exposure to an LD cycle. Because three independent output rhythms of
      the clock (i.e., activity, body temperature, and melatonin rhythms) were equally
      affected, the authors conclude that overt arrhythmicity was due not merely to
      disrupted output pathways but to an altered state of the central pacemaker. The
      authors suggest a qualitative two-oscillator model to explain this phenomenon.
      Their hypothesis assumes that, due to loose coupling, the pacemaker of Djungarian
      hamsters can be driven to a state of zero phase difference between the two
      oscillators, with zero amplitude of their outputs.

PMID- 12054197
TI  - Ontogeny of the daily profile of plasma melatonin in European starlings raised
      under long or short photoperiods.
AB  - Photoperiodic manipulation of young European starlings suggests that their
      reproductive physiology is incapable of responding to a short photoperiod until
      they are fully grown. This study aimed to determine whether the lack of response
      to a short photoperiod is reflected in the daily profile of plasma melatonin
      concentrations. Five-day-old starlings taken from nest boxes showed a significant
      (p < 0.0001) rhythm in plasma melatonin concentrations, with high values during
      night. In nestlings hand-reared from 5 days of age on a long photoperiod (LD
      16:8), equivalent to natural photoperiod at the time, the amplitude of the daily
      rhythm in melatonin increased significantly (p < 0.01) with age until birds were
      fully grown (20 days old). In nestlings reared on a short photoperiod (LD 8:16),
      the daily melatonin profile remained almost identical to that of long photoperiod
      birds until they were fully grown. However, after 20 days old, the duration of
      elevated nighttime melatonin began to extend to encompass the entire period of
      darkness. In contrast, fully grown starlings transferred from a long to a short
      photoperiod had partially adapted to the short photoperiod after 5 days; by 10
      days, the daily melatonin profile was identical to that of birds held chronically
      on a short photoperiod. Thus, consistent with responses of reproductive
      physiology, the pineal of young birds appears to be incapable of perceiving, or
      adapting to, a short photoperiod.

PMID- 12054198
TI  - Phase-dependent effect of room light exposure in a 5-h advance of the sleep-wake
      cycle: implications for jet lag.
AB  - The acute disruption in sleep quality, vigilance levels, and cognitive and
      athletic performance observed after transmeridian flights is presumed to be the
      result of a transient misalignment between the endogenous circadian pacemaker and
      the shifted sleep schedule. Several laboratory and field experiments have
      demonstrated that exposure to bright artificial light can accelerate circadian
      entrainment to a shifted sleep-wake schedule. In the present study, the authors
      investigated whether the schedule of exposure to indoor room light, to which
      urban dwellers are typically exposed, can substantially affect circadian
      adaptation to a simulated eastward voyage. We enrolled 15 healthy young men in a
      laboratory simulation of a Montreal-to-London voyage. Subjects were exposed to 6
      h of room light (mean +/- SD: 379+/-10) prior to bedtime (n = 7) or when on a
      progressively advancing schedule (n = 8) early in the day. The remaining 10 hours
      of wakefulness were spent in dim light (4+/-1 lux). Circadian assessments,
      performed via the constant routine procedure, evaluated the phase of the
      endogenous circadian rhythms of core body temperature and plasma melatonin before
      and after 1 week on the shifted schedule. At the end of the study, only subjects
      exposed to room light on the advancing schedule expressed oscillations of the
      endogenous circadian pacemaker in phase with the new sleep-wake cycle. In this
      group, a mean advance shift of the nadir of core body temperature of +5:22+/-0:15
      h was observed, with parallel shifts in plasma melatonin concentration and
      subjective alertness. The circadian rhythms of subjects exposed to room light
      later in the day remained much more adjusted to the departure than to the
      destination time zone. These results demonstrate that the schedule of exposure to
      room light can substantially affect circadian adaptation to a shifted sleep-wake
      schedule.

PMID- 12054199
TI  - Selection of prepubertal goat oocytes using the brilliant cresyl blue test.
AB  - Brilliant cresyl blue stain allows us to determine the activity of glucose-6
      phosphate dehydrogenase (G6PD), an enzyme synthesized in growing oocytes but with
      decreased activity in oocytes that have finished their growth phase. The
      objective of this study was to evaluate the utility of the brilliant cresyl blue
      (BCB) test as an indirect measure of oocyte growth, in order to select competent
      prepubertal goat oocytes for in vitro embryo production. Oocytes were exposed to
      BCB diluted in PBS and were classified according to their cytoplasm coloration:
      oocytes with a blue cytoplasm or grown oocytes (BCB+) and oocytes without a blue
      cytoplasm or growing oocytes (BCB-). After exposure to different BCB
      concentrations, we evaluated in vitro maturation (IVM), in vitro fertilization
      (IVF) and embryo development parameters. We defined matured oocytes as those
      oocytes that reached the metaphase II (MII) stage after being cultured for 27 h.
      Oocytes showing two pronuclei at 20 h post-insemination were classified as
      normally fertilized oocytes. We assessed embryo development 8 days post
      insemination and recorded the percentage of total embryos, morale and
      blastocysts. The mean percentage of BCB+ oocytes was 29.4%. Mean diameter of BCB+
      oocytes (136.6+/-6.3 microm) was higher (P < 0.001) than that of BCB- oocytes
      (125.5+/-10.2 microm). The percentage of BCB+ oocytes reaching the MII stage
      (81.4%) was higher (P < 0.05) than that of BCB- (52.5%) and control oocytes
      (72.4%). Normal fertilization rate of BCB+ oocytes was also higher (23.5%) than
      that of BCB- (8.2%; P < 0.0001) and control oocytes (11.9%; P < 0.05). The
      percentages of total embryos undergoing development to >8-cell and the morula
      plus blastocyst stages were higher (P < 0.05) in the group of BCB+ (41.3 and
      12.0%, respectively) than in BCB- oocytes (21.3 and 3.6%, respectively). In
      conclusion, the BCB test is a useful way to select more competent prepubertal
      goat oocytes for in vitro embryo production.

PMID- 12054200
TI  - Relation between progesterone concentrations during the early luteal phase and
      follicular dynamics in goats.
AB  - We studied the relationship between progesterone (P4) concentrations early in the
      estrus cycle and follicular dynamics in dairy goats. We used seven untreated
      goats (control group) and six progesterone treated goats (P group) with a
      controlled internal drug release device from Days 0 to 5 (Day 0: day of
      ovulation). We performed daily ultrasonograph during the interovulatory interval
      to determine ovarian change and took daily blood samples to determine serum
      estradiol 17beta (E2) and P4 concentrations by RIA. We divided the control goats
      into 3- (n = 4) and 4-wave goats (n = 3), according to the number of follicular
      waves recorded during the ovulatory cycle. Mean progesterone concentrations
      between Days I and 5 were higher and mean estradiol concentrations between Days 3
      and 5 were lower in 4-wave goats (P4: 3.8+/-0.2 ng/ml; E2: 1.6+/-0.2 pg/ml) than
      in 3-wave goats (P4: 2.0+/-0.5 ng/ml, P < 0.05; E2: 4.4+/-0.9 pg/ml, P < 0.05).
      Wave 2 emerged earlier in 4-wave (Day 4.2+/-0.3) than in 3-wave goats (Day 7.3+/
      0.3, P < 0.05). Three out of six of the progesterone-treated goats had short
      cycles (mean 8.0+/-0.0 days) and ovulated from Wave 1. The other three goats had
      shorter cycles (mean 18.3+/-0.3 days) than the control group (20.0+/-0.2 days; P
      < 0.05), although they were within the normal range of control cycles (shortened
      cycles). In the three treated goats with shortened cycles (two with four waves,
      one with three waves), mean progesterone concentrations between Days I and 5 were
      higher (4.7+/-0.6 ng/ml) than in the 3-wave control goats. In these goats, Wave 2
      emerged at Day 4.3+/-0.3, similar to the time observed in 4-wave goats but
      earlier (P < or = 0.05) than in 3-wave control goats. Overall results confirm a
      relationship between the progesterone levels and the follicular wave turnover
      during the early luteal phase in the goat. Higher progesterone concentrations may
      accelerate follicular turnover probably by an early decline of the negative
      feedback action of the largest follicle of Wave 1. This is followed by an early
      emergence of Wave 2.

PMID- 12054201
TI  - Comparison of two Ovsynch protocols (GnRH versus LH) for fixed timed insemination
      in buffalo (Bubalus bubalis).
AB  - We evaluated the efficiency of replacing GnRH with LH in the ovulation
      synchronization protocol in buffaloes. Buffaloes received GnRH on Day 0,
      (Buserelin; Conceptal, 20 microg), PGF2alpha (Luprostiol; Prosolvin, 15 mg) on
      Day 7 and GnRH (Buserelin; Conceptal, 10 microg; Group 1) or porcine LH (LH;
      Lutropin-V, 12.5 mg; Group 2) on Day 9. In Experiment 1, we studied the
      follicular dynamics of 30 buffaloes (Group 1, n = 15 and Group 2, n = 15). We
      performed ultrasonography every 12 h from Days 0 to 2, then on Day 7 and then
      every 6 h from the time of GnRH or LH treatment (Day 9) until the time of
      ovulation. All females not ovulating by 48 h after the second GnRH or LH
      injection were considered as nonresponders. In Experiment 2, we evaluated 305
      buffaloes (Group 1, n = 154; Group 2, n = 151), using the same two treatments
      studied in Experiment 1. We also recorded and evaluated aspects like parity,
      lactational status, the presence of mucus, and uterine tone at the time of
      artificial insemination (Al). In Experiment 1, ovulation rate after the first
      GnRH was 86.6% (26/30). Ovulation rates were 93.3% (14/15; Group 1) after the
      second dose of GnRH and 93.3% (14/15) after LH (Group 2). Ovulation occurred
      36.4+/-10.4 h after the first GnRH. The interval for treatment to ovulation was
      26.5+/-9.6 h for buffaloes treated with GnRH (Group 1) and 24.4+/-7.9 h for
      buffaloes treated with LH (Group 2); the time of ovulation did not differ
      statistically between the two groups (GnRH versus LH; P > 0.05). In Experiment 2,
      conception rates of the animals AI in the field were 56.5% (Group 1) and 64.2%
      (Group 2), respectively (P = 0.08). The response to the treatment with LH was not
      different to the treatment with GnRH; however, multiparous buffaloes had higher
      conception rates than the primiparous buffaloes in both groups (P > 0.05).
      Buffaloes with mucus at the time of AI in Group 2 had higher conception rates
      than the buffaloes that had mucus in Group 1 (P < 0.05). Uterine tone and
      lactational status did not influence conception rates (P > 0.05). In summary, the
      results showed that both treatments resulted in synchronization of ovulation and
      acceptable conception rates. Therefore, the exogenous injection of LH can
      substitute the GnRH injections in the Ovsynch program in buffaloes.

PMID- 12054202
TI  - Effect of in vitro and in vivo culture on embryo development from prepubertal
      goat IVM-IVF oocytes.
AB  - The aim of this study was to analyze different culture systems on embryo
      development of prepubertal goat oocytes. We compare (i) the effect of the age of
      donor (goat) of oocytes on in vitro maturation, fertilization and subsequent
      embryo development, (ii) the effect of the origin of oviduct cells from coculture
      of prepubertal goat embryo development, and (iii) the effect of in vivo culture
      in rabbit oviducts for 1, 2 and 3 days on the development of prepubertal goat
      embryos produced in vitro. In Experiment 1, at 24 h post-insemination (hpi),
      oocytes from adult goats were allocated in TCM199 with oviduct cells from adult
      goats, and oocytes from prepubertal goats were randomly placed in drops with
      oviduct epithelial cells from adult (aOEC) or prepubertal (pOEC) goats. Cleavage
      rate and embryo development were evaluated at 48 hpi and after 7 days coculture,
      respectively. In Experiment 2, at 24 hpi, prepubertal oocytes were allocated in
      TCM 199 with pOEC. At 40-42 hpi, a group of embryos remained in the coculture
      (control group), and the rest were transferred to rabbit oviducts (three rabbits
      for replicate) for culturing in vivo for 24, 48 and 72 h. After these in vivo
      cultures, embryos were recovered, evaluated and placed in TCM199 with pOEC until
      Day 8 post-insemination. The maturation, fertilization and blastocyst rates did
      not differ significantly between oocytes obtained from adult and prepubertal
      goats. The percentage of blastocysts obtained from prepubertal goat embryos
      cocultured with aOEC or pOEC was also similar (12.1% versus 12.2%). The transfer
      of prepubertal goat embryos to rabbit oviducts for 1, 2 and 3 days did not
      improve the blastocyst rate compared to the control group (9.7, 10.9, 4.1 and
      11.5%, respectively). In conclusion, in our conditions, there were no significant
      differences in embryo development between oocytes obtained from prepubertal and
      adult goats, and the embryo development from prepubertal goat oocytes were
      similar in the different culture systems compared.

PMID- 12054203
TI  - Effect of glutathione synthesis stimulation during in vitro maturation of ovine
      oocytes on embryo development and intracellular peroxide content.
AB  - Cysteamine and beta-mercaptoethanol supplementation of in vitro maturation (IVM)
      medium has been found to increase intracellular glutathione (GSH) content in
      oocytes and to improve embryo development and quality in several species. The
      objective of this experiment was to study the effect of cysteamine and beta
      mercaptoethanol added during IVM of sheep oocytes on GSH synthesis and embryo
      development. Furthermore, we examined if cysteamine addition (hence GSH
      production) had an effect on the reduction of the intracellular peroxide content.
      We matured oocytes obtained from ovaries collected at a slaughterhouse in vitro
      in the presence of 0, 50, 100, and 200 microM cysteamine (Experiment 1) or with
      0, 50, 100, and 200 microM beta-mercaptoethanol (Experiment 2). Following
      fertilization and embryo development, there was a increasing level of morula and
      blastocyst development in the presence of cysteamine, reaching significance in
      the presence of 200 microM (P < 0.05). However, beta-mercaptoethanol did not
      influence on the rate of embryo development. GSH levels were measured in oocytes
      matured in the presence or absence of 200 microM cysteamine (Experiment 3) or 50
      microM beta-mercaptoethanol (Experiment 4), with or without buthionine
      sulfoximide (BSO), an inhibitor of GSH synthesis. Results demonstrated that for
      both cysteamine and beta-mercaptoethanol, intracellular GSH levels increased
      against control values (P < 0.01), which was abolished in the presence of BSO.
      Finally, we reduced intracellular peroxide levels, as measured by the relative
      fluorescence of the intracellular peroxide probe, carboxy-H2DCFDA, in the
      presence of either 200 microM cysteamine or 50 microM beta-mercaptoethanol
      (Experiment 5). These results demonstrate that cysteamine, but not beta
      mercaptoethanol, when present during IVM, stimulates sheep embryo development;
      both cysteamine and beta-mercaptoethanol stimulate GSH synthesis; the increase in
      intracellular GSH is associated with a decrease in peroxide levels within
      oocytes.

PMID- 12054204
TI  - Prevalence of apoptosis and inner cell allocation in bovine embryos cultured
      under different oxygen tensions with or without cysteine addition.
AB  - Supraphysiological oxygen tension during embryo culture can generate reactive
      oxygen species (ROS), which can induce apoptosis. Antioxidants such as thiol
      compounds (cysteine, cysteamine) can be used to prevent ROS damage to the embryo.
      The purpose of this study was to evaluate the prevalence of apoptosis during
      bovine embryo development and to evaluate the effect of the presence or absence
      of cysteine 0.6 mM in modified synthetic oviduct fluid (mSOF) on in vitro
      produced cattle embryos cultured under two different oxygen tensions (5% O2
      versus 20% O2). Effects were assessed by checking embryo development at Days 7, 8
      and 9 and by evaluating Day 9 hatched blastocysts for differentiation by means of
      differential staining and for apoptosis by means of TUNEL-assay. Apoptotic cells
      were present in 94% of Day 7 blastocysts and in 100% of Days 8 and 9 blastocysts.
      Cysteine addition affected Day 8 blastocyst rates in a negative way (P < 0.05)
      regardless of the oxygen tension. In fact, cysteine addition to the mSOF culture
      medium had a negative effect upon embryo development in terms of blastocyst
      rates, hatching rates and apoptotic cell ratio. Embryos cultured under 5% O2 in
      the presence of cysteine, however, possessed significantly higher numbers of ICM
      cells. This finding corroborates the theoretical assumption that antioxidants are
      beneficial for ICM development.

PMID- 12054205
TI  - Zebu (Bos indicus) ovarian preantral follicles: morphological characterization
      and development of an efficient isolation method.
AB  - Preantral follicles are a major source of oocytes, and their utilization as an
      important tool to store large number of female gametes for future use in
      reproductive programs has been investigated. The increasing importance of studies
      in this subject, together with the important role of Zebu cattle in the economy
      of tropical and subtropical countries as well as their well-known differences
      from European cattle, led to this research. The present study aims to determine
      the best size interval for sectioning ovarian tissue to isolate preantral
      follicles from Zebu cows using a tissue chopper and to evaluate the follicular
      quality after isolation. Furthermore, it aims to provide information about the
      Zebu cow preantral follicle population and use this data (as a control) to
      evaluate the effectiveness of the tested isolation method. Testing eight
      different tissue sectioning size intervals, it was possible to conclude that the
      125-microm-section interval is shown to be better than the intervals of 25, 50,
      175 and 200 microm to isolate preantral follicles from Zebu cow ovaries. The 125
      microm interval allowed the recovery of 26,050+/-1611 (mean +/- S.E.M.) preantral
      follicles per one-half ovary, while the number of preantral follicles in situ
      estimated by evaluation of histological sections was 35,288+/-2342 per one-half
      ovary. Thus, the mean (+/-S.E.M.) recovery rate (=[number of preantral follicles
      isolated/number of preantral follicles in situ in the same ovary] x 100) was
      74.3+/-4.3%. The morphometrical analysis showed that Bos indicus preantral
      follicles are similar to B. taurus preantral follicles based on previous reports.
      In conclusion, this study showed that a simple, mechanical method can be used
      effectively to isolate a large number of intact preantral follicles from Zebu cow
      ovaries, with a high recovery rate.

PMID- 12054206
TI  - Synchronization of estrus in beef heifers using either melengesterol acetate
      (MGA)/prostaglandin or MGA/Select Synch.
AB  - The objective of this study was to evaluate synchronization, conception, and
      pregnancy rates of yearling beef heifers synchronized with either the Select
      Synch protocol preceded by 7 days of MGA feeding (MGA/Select Synch) or the
      traditional MGA/PGF protocol. Heifers in the MGA/Select Synch group (n = 402)
      were fed MGA (0.5 mg/day/head) for 7 days, received an injection of GnRH (100
      microg) the day following the last MGA feeding and an injection of PGF (25 mg) 7
      days after GnRH. Heifers in the MGA/PGF group (n = 394) received MGA (0.5
      mg/day/head) for 14 days, followed by an injection of PGF (25 mg) 17 days later.
      Synchronization rates tended (P = 0.08) to be higher for the MGA/Select Synch
      (82%) compared to the MGA/PGF (77%)-treated heifers. Conception and pregnancy
      rates to AI were similar (P > 0.10), 57 and 46% for the MGA/Select Synch heifers
      and 61 and 47% for the MGA/PGF heifers, respectively. Mean estrous response (h)
      was earlier (P < 0.05) for the MGA/Select Synch versus MGA/PGF treatment, 56
      versus 61 h post-PGF treatment, respectively. In summary, short-term (7 days) MGA
      feeding preceding the Select Synch protocol produced similar synchronization,
      conception, and pregnancy rates as the traditional MGA/PGF protocol.

PMID- 12054207
TI  - Capacitation and acrosomal exocytosis are enhanced by incubation of stallion
      spermatozoa in a commercial semen extender.
AB  - Preserved stallion semen often has decreased spermatozoal motility and fertility
      that can vary significantly between individual stallions. It is not known whether
      the medium used for extending equine sperm contributes to these decreases by
      inducing premature capacitation during storage. If spermatozoa undergo
      capacitation or acrosome reaction prior to insemination, this could result in a
      diminished capacity to penetrate the cumulus mass and fertilize the egg. We
      hypothesized that skim milk-based semen extenders, similar to those used in
      cooled storage, stabilize sperm membranes and prolong sperm motility and
      longevity. However, this could decrease the efficiency of sperm to undergo
      subsequent capacitation in vivo. This study was designed to evaluate the effects
      from two media on sperm function. Spermatozoal motility was analyzed,
      intracellular calcium was measured, and the ability of sperm to undergo acrosome
      reaction was compared after incubation in a skim milk extender (SME) and Tyrode's
      medium containing albumin, lactate, and pyruvate (TALP) at 37 degrees C. Results
      suggest that the SME facilitated capacitation as detected by an increase in both
      intracellular calcium and acrosome reactions, and a decrease in motility, as
      compared to TALP. Our data support a shortened functional lifespan for equine
      sperm in skim milk extender, which indicates that further refinements in cooled
      semen preservation are required to improve fertility of transported equine semen.

PMID- 12054208
TI  - Improvement of reproductive performance in crossbred zebu anestrous primiparous
      cows by treatment with norgestomet implants or 96 h calf removal.
AB  - The aim of the present study was to compare the effect of norgestomet implants
      (NI) and calf removal (CR) for 96 h on estrus induction and first service
      fertility in crossbred zebu primiparous anestrous cows after 120 days postpartum.
      A total of 152 cows in a tropical environment were allotted to three experimental
      groups: CR for 96 h (n = 51), NI for 9 days plus 500 IU of PMSG at implant
      removal (n = 51) and a control group (CG) without treatment (n = 50). Estrous
      rate (%) and mean interval to first estrus (days) were 50.9 and 26.3+/-6.8; 60.7
      and 13.8+/-6.8; 16.0% and 61.8+/-5.9 days for groups CR, NI and CG, respectively.
      CR and NI were statistically similar, however, both groups were different (P <
      0.01) when compared with CG. Calving interval to first service and to conception
      were: CR: 151.2+/-8.4 and 157.8+/-21.4; NI: 145.2+/-8.5 and 150.9+/-21.3; CG:
      186.8+/-7.3 and 201.0+/-18.5. A difference (P < 0.01) was found in both intervals
      when comparing the CR and NI with CG, with longer intervals for cows in the CG
      group. First service conception rates were 61.5, 67.7 and 62.5% for groups CR, NI
      and CG, respectively, and were not different (P > 0.05). These results
      demonstrate the efficacy of NI + PMSG or temporary CR for 96 h in inducing a
      fertile estrus and shortening the interval to estrus and to conception in
      primiparous crossbred anestrous zebu cows in the tropics.

PMID- 12054209
TI  - Effect of precocious collection on semen output and quality in young Holstein
      bulls.
AB  - Semen production units compete heavily with each other, so they tend to select
      and collect bulls at the earliest possible age, even before puberty, in order to
      reduce the interval between generations. This study is a retrospective analysis
      of the effect of precocious collection on semen quality in Holstein bulls. The
      semen parameters of early- and late-maturing bulls collected before and after 410
      days of age, respectively, were compared over two periods, 1991-1995 and 1997
      1999. These periods were defined in relation to the collection rhythms (three
      collections of two ejaculates at 15 days interval before 1996 and adaptation of
      the collection rhythms to individual physiological capacity after 1996) and the
      collection conditions. The effects of age, precocious collection and the
      interaction between age and precocious collection on mean semen parameters
      (volume of the ejaculate, sperm motility, percent of motile spermatozoa per
      ejaculate, total sperm concentration and mobile sperm concentration) measured on
      collections 1-6 (n = 358 for 1991-1995 and n = 121 for 1997-1999), 7-12 (n = 255
      for 1991-1995 and n = 80 for 1997-1999) and 13-18 (n = 92 for 1991-1995 and n =
      36 for 1997-1999) were studied by covariance analysis. The semen quality of bulls
      collected at the early age differed from that of bulls collected after 410 days
      of age for the first period when the collection rhythm was intense. No effect of
      precocious collection was evidenced for the second period, suggesting the
      importance of individual adaptation of the collection rhythm to sexual maturation
      in young bulls. Early collections at a semen production unit reduced the time
      needed to obtain the number of insemination straws required for the progeny
      testing program by 40 days. Early sperm collection is, thus, of economic and
      technical interest in well managed semen production units.

PMID- 12054210
TI  - Effect of follicular size on meiotic and developmental competence of porcine
      oocytes.
AB  - In several species, the developmental competence of the oocyte is acquired
      progressively during late follicular growth, after the acquisition of the
      competence to resume and complete meiosis. In the pig, full meiotic competence of
      the oocyte is reached in ovarian follicles with a diameter of 3 mm or more.
      However, there is no information about developmental competence acquisition. We
      analyzed the ability of oocytes from three foll icular size classes to resume and
      complete meiosis, to be fertilized, and to develop in vitro to the blastocyst
      stage. A total of 941 follicles were dissected from slaughterhouse gilt ovaries
      and classified as small (<3 mm, n = 330), medium (3-5 mm, n = 373), or large (>5
      mm, n = 238). The cumulus-oocyte complexes recovered from these follicles were
      submitted to in vitro maturation for 44 h in TCM199 supplemented with 10 ng/ml
      EGF, 400 ng/ml pFSH and 570 microM cysteamine; in vitro fertilized for 18 h in
      mTBM with 10(5) frozen-thawed percoll-selected sperms/ml; and developed for 7
      days in mSOF. Samples of oocytes or presumptive zygotes were fixed and stained at
      the end of maturation and fertilization. Groups of oocytes were cultured for 3 h
      in the presence of 35S-methionine before or after maturation for SDS-PAGE
      analysis of protein neosynthesis. More oocytes originating from medium and large
      follicles were competent for maturation than oocytes from small follicles (77 and
      86% of metaphase II, respectively, versus 44%, P < 0.05). More oocytes from
      medium and large follicles werepenetratedby spermatozoa during in vitro
      fertilization, resulting in significantly more oocytes presenting two or more
      pronuclei at the end of fertilization (73 and 77% for medium and large follicles,
      respectively, versus 53% for small follicles, P < 0.05). More oocytes from medium
      and large follicles developed to the blastocyst stage (14 and 23%, respectively)
      than those from small follicles (3%, P < 0.05), even if the development rates
      were corrected by the maturation or fertilization rates. It is concluded that a
      high proportion of oocytes harvested from follicles of less than 3 mm in the pig
      are not fully competent for meiosis and are cytoplasmically deficient for
      development.

PMID- 12054211
TI  - Transfer of porcine embryos through mini-laparotomy.
AB  - The aim of this experiment was to examine the suitability of mini-laparotomy for
      transferring embryos in pigs. Expanded blastocysts collected from estrus-induced
      prepuberal gilts were transferred to the uterus of synchronous recipients. Each
      recipient received 18 embryos transferred unilaterally either by conventional
      laparotomy (n = 20), mini-laparotomy (n = 15) or laparoscopy (n = 14). The mini
      laparotomy consisted of a midventral incision of 4 cm enabling the surgeon to
      grasp a uterine horn with two fingers and exteriorize about 3 cm of it. To close
      the suture wound, only three or four interrupted skin sutures are required.
      Pregnancy rates after conventional surgery, mini-laparotomy and laparoscopy were
      60.67 and 21%, respectively. Corresponding litter size was 7.4, 6.2 and 6.0 and
      total embryo survival 25, 23 and 7%. The differences in pregnancy rate and total
      embryo survival between conventional and mini-surgery were negligible, whereas
      between laparoscopy and the other two techniques it was significant. It may be
      concluded that, with a little practice, the time saving and less traumatic mini
      laparotomy is a practicable alternative to conventional surgery.

PMID- 12054212
TI  - Oral administration of pharmacological doses of vitamins C and E reduces
      reproductive fitness and impairs the ovarian and uterine functions of female
      mice.
AB  - This study aims to ascertain whether oral administration of pharmacological doses
      of Vitamins C and E has any detrimental effect on reproductive fitness of female
      mice. We fed hybrid female mice from the first day of weaning a standard diet
      supplemented or not supplemented with pharmacological doses of Vitamins C and E.
      At the age of 28 weeks, we individually caged females with a male for the rest of
      their reproductive life. We performed a series of mating experiments to ascertain
      the number of oocytes ovulated and the potential for embryo development in vitro
      to the blastocyst stage and in vivo to Day 12 of gestation. The antioxidant diet
      decreased the frequency of litters, litter size, total number of offspring born
      and survival of male pups to weaning. This effect was associated with lower
      number of corpora lutea in the left ovary, decreased percentage of viable
      fetuses, and higher number of fetal resorptions in the left uterine horn when
      compared to the control group. The strategy of supplementing the diet with
      antioxidant vitamins to prevent the age associated decrease in reproductive
      potential should not be implemented in human beings until a safe and efficient
      diet is designed.

PMID- 12054213
TI  - Effects of acetoacetate and D-beta-hydroxybutyrate on bovine in vitro embryo
      development in serum-free medium.
AB  - It is known that the ketone bodies acetoacetate and D-beta-hydroxybutyrate can be
      metabolized by the early bovine embryo for in vitro development. In the present
      work, we report experiments leading to the culture of bovine embryos in the
      absence of serum. In vitro-produced bovine zygotes were cultured in modified
      synthetic oviduct fluid medium supplemented with acetoacetate derivatives,
      acetoacetate and D-beta-hydroxybutyrate. Acetoacetate and its derivatives
      prevented blastocysts from forming in the absence of serum during the whole
      culture period. However, from Days 6 to 8 of culture in the absence of serum,
      acetoacetate did not affect development as compared to controls containing
      lactate and pyruvate or no substrate. Interestingly, D-beta-hydroxybutyrate
      stimulated blastocyst and expansion development, and allowed lipid mobilization.
      In feeder cells coculture, embryos produced with D-beta-hydroxybutyrate showed
      improved hatching. Embryos cultured in D-beta-hydroxybutyrate were viable upon
      transfer to recipients, although no pregnancies were confirmed later by
      ultrasonic scanning. The protective effect of serum upon embryos cultured in
      medium containing acetoacetate is apparently not required in the presence of D
      beta-hydroxybutyrate.

PMID- 12054214
TI  - Myometrial activity around estrus in sows: spontaneous activity and effects of
      estrogens, cloprostenol, seminal plasma and clenbuterol.
AB  - A new, nonsurgical, open-end catheter technique was used to study spontaneous
      uterine activity around estrus in sows, and the effects of estrogens, seminal
      plasma, cloprostenol, and clenbuterol on uterine activity. In the first
      experiment, uterine activity was studied in 14 multiparous, cyclic sows, during
      one or more estrous cycles, from day -4 to day 4 of the cycle (day 0: first day
      of standing estrus). From a few days before estrus until estrus, the percentage
      of sows showing any uterine contractions increased from 55 to 100%, and frequency
      and mean amplitude of uterine contractions for these sows increased from 15 to
      22/h, and from 20 to 40 mmHg on average. After estrus, uterine activity
      decreased. There were large differences between sows in uterine activity, which
      were consistent over the days of the cycle. In the second experiment, 11.5 microg
      of estrogens in 100 ml saline (n = 17), 100 ml seminal plasma (n = 5), 1 mg
      cloprostenol in 100 ml saline (n = 10), 0.30 mg clenbuterol in 100 ml saline (n =
      11), or 100 ml saline (n = 5) was infused IU, after recording spontaneous
      activity. Infusion with saline or seminal plasma did not affect uterine activity.
      Estrogens increased frequency of contractions. Cloprostenol increased both
      frequency and amplitude of contractions. Clenbuterol reduced both frequency and
      amplitude of contractions. In conclusion, this study shows that spontaneous
      uterine activity in sows is increased around estrus, and it supports the role of
      estrogens in boar seminal plasma in affecting uterine activity around mating.
      Further, this study has yielded possible tools to study the relation between
      uterine activity and sperm transport.

PMID- 12054215
TI  - Scientific whaling.

PMID- 12054216
TI  - Corynebacterium aurimucosum sp. nov. and emended description of Corynebacterium
      minutissimum Collins and Jones (1983).
AB  - Two coryneform bacteria isolated from human clinical specimens were characterized
      by phenotypic and molecular taxonomic methods. Chemotaxonomic investigations
      revealed the presence of cell-wall chemotype IV and short-chain mycolic acids
      consistent with the genus Corynebacterium sensu stricto. Comparative 16S rRNA
      gene sequence analysis showed that the two strains are genealogically highly
      related (99.8% sequence similarity) and constitute a new subline within the genus
      Corynebacterium, with Corynebacterium minutissimum as their nearest phylogenetic
      neighbours (98.8% sequence similarity). However, DNA-DNA hybridization
      experiments demonstrated unambiguously that the isolates are genealogically
      distinct from Corynebacterium minutissimum (42% homology). Biochemical testing
      indicated that the two isolates were hardly differentiated from Corynebacterium
      minutissimum. Based on both phenotypic and phylogenetic evidence it is proposed
      that these isolates be classified as a new species, Corynebacterium aurimucosum
      sp. nov. The type strain of Corynebacterium aurimucosum is represented by strain
      IMMIB D-1488T (= DSM 44532T = NRRL B-24143T).

PMID- 12054217
TI  - Cellular fatty acids as chemotaxonomic markers of the genera Anabaena,
      Aphanizomenon, Microcystis, Nostoc and Planktothrix (cyanobacteria).
AB  - The cellular fatty acid content of 22 cyanobacterial strains belonging to the
      genera Anabaena, Aphanizomenon, Calothrix, Cylindrospermum, Nostoc, Microcystis
      and Planktothrix were analysed. The identities of the major peaks were confirmed
      by MS. Correspondence analysis of the data revealed three distinct groups formed
      by the Microcystis strains, the Nostoc/Planktothrix strains and the
      Anabaena/Aphanizomenon/Cylindrospermum strains. The Calothrix strain did not
      cluster with the other heterocystous cyanobacteria, supporting its morphological
      classification separate from the Nostocaceae family. The presence of large
      amounts of the fatty acids 18:30omega6,9,12c and 18:0 iso distinguished the
      Microcystis strains from the other cyanobacteria studied. The high content of
      16:1omega7c grouped the Nostoc strains with the Planktothrix strains. A free
      living strain of Nostoc contained 16:1omegao5c and 16: 1omega7c (about 1: 1),
      separating it from the symbiotic Nostoc strain and the Planktothrix strains. the
      strains of Anabaena, Aphanizomenon and Cylindrospermum grouped tightly and were
      characterized by the presence of 16:1omega9c and 16:0 anteiso fatty acids.
      Correspondence analysis of Anabaena, Aphanizomenon and Cylindrospermum showed
      that all hepatotoxic Anabaena strains grouped together, whereas the non-toxic and
      neurotoxic Anabaena strains grouped with the non-toxic Aphanizomenon strains.

PMID- 12054218
TI  - Arthrobacter roseus sp. nov., a psychrophilic bacterium isolated from an
      antarctic cyanobacterial mat sample.
AB  - Strain CMS 90rT, a red-pigmented bacterium, was isolated from a cyanobacterial
      mat sample from a pond located in McMurdo, Antarctica. Based on its
      chemotaxonomic and phylogenetic properties, strain CMS 90r(T) was identified as a
      member of group I of Arthrobacter. It shared 16S rDNA similarity of 98% with
      Arthrobacter oxydans ATCC 14358T and Arthrobacter polychromogenes ATCC 15216T,
      while DNA-DNA similarities determined for these three organisms were less than
      70%. It also differed from all 17 reported Arthrobacter species with A3alpha
      variant peptidoglycan in that it possessed a unique peptidoglycan (Lys-Gly-Ala3)
      and contained galactose, glucose, ribose and rhamnose as cell-wall sugars. These
      data and the presence of diagnostic phenotypic traits support the description of
      CMS 90r(T) as a novel species of Arthrobacter, for which the name Arthrobacter
      roseus sp. nov. is proposed. The type strain is strain CMS 90r(T) (= MTCC 3712T =
      DSM 14508T).

PMID- 12054219
TI  - Bannoa hahajimensis gen. nov., sp. nov., and three related anamorphs,
      Sporobolomyces bischofiae sp. nov., Sporobolomyces ogasawarensis sp. nov. and
      sporobolomyces syzygii sp. nov., yeasts isolated from plants in Japan.
AB  - Fourteen ballistoconidium-forming yeast strains were isolated from leaves of
      plants collected in the Ogasawara Islands, which are isolated islands in the
      Pacific Ocean, about 1,000 km south of the Japanese mainland, in the subtropical
      zone. The 14 isolates were characterized by the absence of xylose in whole-cell
      hydrolysates, the presence of Q-10(H2) as the major ubiquinone isoprenologue, G+C
      contents of 47.6-52.0 mol%, the inability to ferment sugars or to assimilate
      nitrate and positive Diazonium blue B and urease reactions. They formed a
      phylogenetically coherent cluster within the Erythrobasidium lineage in the
      Urediniomycetes of the Basidiomycota based on 18S rDNA sequences. Analyses of the
      nucleotide sequences of internal transcribed spacer regions and DNA
      complementarity showed that four genospecies were recognized among the 14
      isolates. A mating reaction was observed in one of the four genospecies, which
      produced one-celled basidia on dikaryotic hyphae with clamp connections. On the
      basis of the morphological, physiological, chemotaxonomic and phylogenetic
      analyses, a new teleomorphic genus, Bannoa, is proposed, in which one novel
      species is described, Bannoa hahajimensis gen. nov., sp. nov. (type strain OK
      248(T) = JCM 10336T = CBS 9039(T)). The other three anamorphic genospecies are
      described as Sporobolomyces bischofiae sp. nov. (type strain OK-257T = JCM 10338T
      =CBS 9041T), Sporobolomyces ogasawarensis sp. nov. (type strain OK-14T = JCM
      10326T = CBS 9038T) and Sporobolomyces syzygii sp. nov. (type strain OK-227T =
      JCM 10337T = CBS 9040T.

PMID- 12054220
TI  - Cryptococcus nyarrowii sp. nov., a basidiomycetous yeast from Antarctica.
AB  - In December 1997, 196 soil and snow samples were collected from Vestvold Hills,
      Davis Base, Antarctica. Two isolates, CBS 8804T (pink colonies) and CBS 8805
      (yellow colonies), were shown by proteome analysis and DNA sequencing to
      represent the same species. Results from the sequencing of the D1/D2 region of
      the large rDNA subunit placed this species in the hymenomycetous tree in a unique
      sister clade to the Trichosporonales and the Tremellales. The clade consists of
      Holtermannia corniformis CBS 6979 and CBS strains 8804T, 8805, 8016, 7712, 7713
      and 7743. Morphological and physiological characteristics placed this species in
      the genus Cryptococcus, with characteristics including the assimilation of D
      glucuronate and myo-inositol, no fermentation, positive Diazonium blue B and
      urease reactions, absence of sexual reproduction and production of starch-like
      compounds. Fatty acid analysis identified large proportions of polyunsaturated
      lipids, mainly linoleic (C18:2) and, to a lesser extent, linolenic (C18:3) acids.
      On the basis of the physiological and phylogenetic data, isolates CBS 8804T and
      CBS 8805 are described as Cryptococcus nyarrowii sp. nov.

PMID- 12054221
TI  - Correction of the connecting vowel and gender of the specific epithet in the name
      Sphingomonas macrogoltabidus Takeuchi et al. 1993 to Sphingomonas
      macrogolitabida.
AB  - In accordance with the Bacteriological Code (1990 Revision), the connecting vowel
      and gender of the specific epithet macrogoltabidus in combination with the
      generic name Sphingomonas must be -i- and the ending must be changed to -a to
      agree with the gender of the generic name, respectively. Thus Sphingomonas
      macroboltabidus Takeuchi et al. 1993 should be Sphingomonas macrogolitabida
      corrig. Takeuchi et al. 1993.

PMID- 12054222
TI  - Bacillus dysentericus (sic) 1897 was the first taxonomic rather than Bacillus
      dysenteriae 1898.
AB  - The basonym of Shigella dysenteriae (Shiga 1898) Castellani and Chalmers 1919 was
      first and officially proposed in 1897 as Bacillus dysentericus (sic) in
      Saikingaku Zasshi, published in Japan. In accordance with Section 6 (Citation of
      Authors and Names) of the Bacteriological Code (1990 Revision), the year of the
      first proposal of Shigella dysenteriae has to be corrected from Bacillus
      dysenteriae 1898 to Bacillus dysentericus (sic) 1897.

PMID- 12054223
TI  - Report of the ad hoc committee for the re-evaluation of the species definition in
      bacteriology.
AB  - An ad hoc committee for the re-evaluation of the species definition in
      bacteriology met in Gent, Belgium, in February 2002. The committee made various
      recommendations regarding the species definition in the light of developments in
      methodologies available to systematists.

PMID- 12054225
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM. International Journal of Systematic and
      Evolutionary Microbiology.

PMID- 12054224
TI  - Proposed minimal standards for describing new taxa of the family
      Flavobacteriaceae and emended description of the family.
AB  - In this paper minimal standards for the description of new genera and cultivable
      species in the family Flavobacteriaceae are proposed in accordance with
      Recommendation 30b of the Bacteriological Code (1990 Revision). In addition to
      specified phenotypic characteristics, the description of new species should be
      based on DNA-DNA hybridization data, and the placement of new taxa should be
      consistent with phylogenetic data derived from 16S rRNA sequencing. An emended
      description of the family is also proposed as several new taxa have been
      described since 1996. These proposals have been endorsed by the members of the
      Subcommittee on the taxonomy of Flavobacterium and Cytophaga-like bacteria of the
      International Committee on Systematics of Prokaryotes.

PMID- 12054226
TI  - Notification that new names and new combinations have appeared in volume 52, part
      2, of the IJSEM. International Journal of Systematic and Evolutionary
      Microbiology.

PMID- 12054227
TI  - 'Candidatus mycoplasma haemodidelphidis' sp. nov., 'Candidatus mycoplasma
      haemolamae' sp. nov. and Mycoplasma haemocanis comb. nov., haemotrophic parasites
      from a naturally infected opossum (Didelphis virginiana), alpaca (Lama pacos) and
      dog (Canis familiaris): phylogenetic and secondary structural relatedness of
      their 16S rRNA genes to other mycoplasmas.
AB  - The 16S rRNA sequence of newly characterized haemotrophic bacteria in an opossum
      (Didelphis virginiana) and alpaca (Lama pacos) was determined. In addition, the
      16S rRNA sequence of a haemotrophic parasite in the dog (Canis familiaris) was
      determined. Sequence alignment and evolutionary analysis as well as secondary
      structural similarity and signature nucleotide sequence motifs of their 16S rRNA
      genes, positioned these organisms in the genus Mycoplasma. The highest scoring
      sequence similarities were 16S rRNA genes from haemotrophic mycoplasma species
      (Haemobartonella and Eperythrozoon spp.). However, the lack of several higher
      order structural idiosyncrasies used to define the pneumoniae group, suggests
      that these organisms and related haemotrophic mycoplasmas represent a new group
      of mycoplasmas. It is recommended that the organisms be named 'Candidatus
      Mycoplasma haemodidelphidis', 'Candidatus Mycoplasma haemolamae' and Mycoplasma
      haemocanis comb. nov., to provide some indication of the target cell and host
      species of these parasites, and to reflect their phylogenetic affiliation.

PMID- 12054228
TI  - Pasteurella skyensis sp. nov., isolated from Atlantic salmon (Salmo salar L.).
AB  - From four separate incidents of disease in farmed Atlantic salmon over a four
      year period, gram-negative rod-shaped bacteria were consistently isolated by
      culture on sea-water blood agar. Biochemical and physiological tests indicated
      that the organism was related to the family Pasteurellaceae, and this was
      confirmed from the 16S rRNA gene sequence. Comparison of the 16S rRNA gene
      sequence with those of 45 members of the Pasteurellaceae showed that the closest
      phylogenetic relationship was with an organism termed 'Pasteurella phocoenarum',
      isolated from a porpoise, for which the 16S rRNA gene sequence has been recorded
      but for which the properties have yet to be published. It is proposed that this
      bacterium isolated from salmon should be classified as a new species, namely
      Pasteurella skyensis sp. nov. The type strain of Pasteurella skyensis sp. nov. is
      strain 95A1T (= NCTC 13204T = NCIMB 13593T).

PMID- 12054230
TI  - Mitsuokella jalaludinii sp. nov., from the rumens of cattle in Malaysia.
AB  - Five strains of phytase-producing, gram-negative, non-spore-forming, non-motile,
      small, stout, rod-shaped, strictly anaerobic, fermentative bacteria were isolated
      from the rumens of cattle in Malaysia. All five strains had morphological,
      physiological and biochemical features in common. Although these strains had many
      physiological and biochemical characteristics that were identical to those of the
      Mitsuokella multacida type strain (ATCC 27723T), they could be distinguished from
      this species by means of the following characteristics: a smaller cell size (1.2
      2.4 microm long and 0.6-0.8 microm wide); a lower final pH value (3.8-4.0) in
      peptone/yeast extract/glucose broth; inhibition by 0.001% brilliant green;
      insensitivity to kanamycin (100 microg ml(-1)) and penicillin (10 microg ml(-1));
      a higher optimum growth temperature (approx. 42 degrees C); the ability to grow
      at 45 and 47 degrees C; the ability to ferment glycerol, sorbitol and amidon; and
      the inability to ferment mannitol, rhamnose, D-tagatose and melezitose. The G+C
      content of the type strain (M 9T) of these five strains was 56.9 mol%. Analysis
      of the 16S rRNA gene sequence of type strain M 9T indicated that the strain falls
      within the genus Mitsuokella. The sequence similarity between type strain M 9T
      and Mitsuokella multacida was 98.7%. The DNA-DNA relatedness between type strain
      M 9T and Mitsuokella multacida type strain DSM 20544T (= ATCC 27723T) was 63.8%,
      indicating that, in spite of a high level of similarity for the 16S rRNA gene
      sequence, type strain M 9T is independent of Mitsuokella multacida at the species
      level. On the basis of these results, a new species, Mitsuokella jalaludinii sp.
      nov., is proposed for these strains. The type strain is M 9T (= DSM 13811T = ATCC
      BAA-307T).

PMID- 12054229
TI  - Aeromonas hydrophila subsp. dhakensis subsp. nov., isolated from children with
      diarrhoea in Bangladesh, and extended description of Aeromonas hydrophila subsp.
      hydrophila (Chester 1901) Stanier 1943 (approved lists 1980).
AB  - A group of 10 Aeromonas hydrophila-like strains referred to as group BD-2, which
      mainly comprised haemolytic and cytotoxic isolates from diarrhoeal children in
      Bangladesh, was subjected to a polyphasic taxonomic study including fluorescent
      amplified fragment length polymorphism (FAFLP) and ERIC-PCR fingerprinting,
      microplate DNA-DNA hybridization and extensive phenotypic characterization.
      Comparison of FAFLP and ERIC-PCR genotypic profiles indicated that the group BD-2
      isolates constituted a separate taxon that was most closely related to A.
      hydrophila DNA hybridization group (HG) 1. Determination of DNA-DNA hybridization
      values with type and reference strains of all known Aeromonas taxa revealed that
      the BD-2 group represented a homogeneous taxon (internal DNA homology, 77-94%)
      that exhibited 78-92% DNA relatedness with the type strain of A. hydrophila HG1.
      These results indicated that the BD-2 group belongs genotypically to A.
      hydrophila HG1, but examination of 152 phenotypic characteristics revealed that
      the group BD-2 isolates differed from representatives of HG1 in eight biochemical
      properties. The diagnostic value of at least three of these tests, namely
      utilization of urocanic acid and L-arabinose and acid production from L
      arabinose, has been confirmed outside this study by other workers. Collectively,
      the genotypic and phenotypic data reported suggest that the BD-2 group represents
      a subspecies of A. hydrophila, for which the name Aeromonas hydrophila subsp.
      dhakensis subsp. nov. is proposed. Its type strain is P21T (= LMG 19562T= CCUG
      45377T). An extended description of A. hydrophila subsp. hydrophila (Chester
      1901) Stanier 1943 (Approved Lists 1980) is given.

PMID- 12054231
TI  - Geoglobus ahangari gen. nov., sp. nov., a novel hyperthermophilic archaeon
      capable of oxidizing organic acids and growing autotrophically on hydrogen with
      Fe(III) serving as the sole electron acceptor.
AB  - A novel, regular to irregular, coccoid-shaped, anaerobic, Fe(III)-reducing
      microorganism was isolated from the Guaymas Basin hydrothermal system at a depth
      of 2000 m. Isolation was carried out with a new technique using Fe(III) oxide as
      the electron acceptor for the recovery of colonies on solid medium. The isolate,
      designated strain 234T, was strictly anaerobic and exhibited a tumbling motility.
      The cells had a single flagellum. Strain 234T grew at temperatures between 65 and
      90 degrees C, with an optimum at about 88 degrees C. The optimal salt
      concentration for growth was around 19 g l(-1). The isolate was capable of growth
      with H2 as the sole electron donor coupled to the reduction of Fe(III) without
      the need for an organic carbon source. This is the first example of a
      dissimilatory Fe(III)-reducing micro-organism capable of growing autotrophically
      on hydrogen. In addition to molecular hydrogen, strain 234T oxidizes pyruvate,
      acetate, malate, succinate, peptone, formate, fumarate, yeast extract, glycerol,
      isoleucine, arginine, serine, glutamine, asparagine, stearate, palmitate,
      valerate, butyrate and propionate with the reduction of Fe(III). This isolate is
      the first example of a hyperthermophile capable of oxidizing long-chain fatty
      acids anaerobically. Isolate 234T grew exclusively with Fe(III) as the sole
      electron acceptor. The G+C content was 58.7 mol%. Based on detailed analysis of
      its 16S rDNA sequence, G+C content, distinguishing physiological features and
      metabolism, strain 234T is proposed to represent a novel genus within the
      Archaeoglobales. The name proposed for strain 234T is Geoglobus ahangari gen.
      nov., sp. nov..

PMID- 12054232
TI  - Haloferax alexandrinus sp. nov., an extremely halophilic canthaxanthin-producing
      archaeon from a solar saltern in Alexandria (Egypt).
AB  - An extremely halophilic red micro-organism designated strain TM(T) was isolated
      from a solar saltern in Alexandria, Egypt. The micro-organism stains gram
      negative, is very pleomorphic, non-motile and strictly aerobic and requires at
      least 10 g NaCl l(-1) for growth. The growth optimum is 250 g NaCl l(-1). Growth
      is also observed over a wide range of MgSO4 concentrations (10-40 g l(-1)).
      Aerobic reduction of nitrate without gas production was detected. Cells grew
      aerobically in a minimal salts medium containing ammonium chloride and glucose.
      Strain TM(T) produced acid from fructose, glucose, rhamnose, maltose and
      glycerol. The G+C content of the DNA was 59.5+/-0.3 mol %. On the basis of polar
      lipid analysis, the isolate belonged to the genus Haloferax. Analysis of the 16S
      rDNA sequence showed the highest similarity (>99%) to be to the type strain
      Haloferax volcanii. Although the spectrum of antibiotic susceptibility was
      similar to that of validly described species of the genus Haloferax, the strain
      could be distinguished from them by its different response to josamycin and
      rifampicin. Strain TM(T) is unique within the genus Haloferax in producing
      canthaxanthin. Comparative analysis of phenotypic properties and DNA-DNA
      hybridization between strain TM(T) and Haloferax species supported the conclusion
      that TM(T) is a novel species within this genus, for which the name Haloferax
      alexandrinus sp. nov. is proposed. The type strain is TM(T) (= JCM 10717T = IFO
      16590T).

PMID- 12054233
TI  - Phylogenetic study of the genus Oceanospirillum based on 16S rRNA and gyrB genes:
      emended description of the genus Oceanospirillum, description of Pseudospirillum
      gen. nov., Oceanobacter gen. nov. and Terasakiella gen. nov. and transfer of
      Oceanospirillum jannaschii and Pseudomonas stanieri to Marinobacterium as
      Marinobacterium jannaschii comb. nov. and Marinobacterium stanieri comb. no.
AB  - The phylogenetic relationships of Oceanospirillum strains were analysed by using
      the nucleotide sequences of 16S rRNA and gyrB genes. Results from sequence
      analysis demonstrated that the Oceanospirillum core group consisted of four
      species, Oceanospirillum linum, Oceanospirillum maris, Oceanospirillum
      beijerinckii and Oceanospirillum multiglobuliferum, with enough distance to
      separate them as different species. However, four other Oceanospirillum species
      occupied taxonomic positions separate from the Oceanospirillum core group:
      Oceanospirillum jannaschii, Oceanospirillum japonicum and Oceanospirillum kriegii
      in the gamma-Proteobacteria and Oceanospirillum pusillum in the alpha
      Proteobacteria. Oceanospirillum jannaschii clustered with Marinobacterium
      georgiense, Pseudomonas iners and Pseudomonas stanieri on the basis of
      phylogenetic analysis of 16S rRNA and gyrB genes. The other three species did not
      cluster with known genera. Also, the sequence similarity values of the gyrB genes
      between the three subspecies of Oceanospirillum maris and those between the two
      subspecies of Oceanospirillum beijerinckii were above 99%. The close
      relationships between the subspecies of Oceanospirillum maris and of
      Oceanospirillum beijerinckii were further supported by similar physiological
      properties and high DNA-DNA hybridization values, suggesting that these
      subspecies should not be regarded as valid. From these results, Oceanospirillum
      sensu stricto should be defined to consist of Oceanospirillum linum,
      Oceanospirillum maris, Oceanospirillum beijerinckii and Oceanospirillum
      multiglobuliferum. We propose to create the following new genera: Pseudospirillum
      gen. nov. for Oceanospirillum japonicum as Pseudospirillum japonicum comb. nov.;
      Oceanobacter gen. nov. for Oceanospirillum kriegii as Oceanobacter kriegii comb.
      nov.; and Terasakiella gen. nov. for Oceanospirillum pusillum as Terasakiella
      pusilla comb. nov. The transfer is proposed of Oceanospirillum jannaschii and
      Pseudomonas stanieri to Marinobacterium as Marinobacterium jannaschii comb. nov.
      and Marinobacterium stanieri comb. nov. Furthermore, Pseudomonas iners should be
      reclassified as a strain of Marinobacterium georgiense. Finally, the subspecies
      of Oceanospirillum maris (O. maris subsp. maris, O. maris subsp. hiroshimense and
      O. maris subsp. williamsae) and Oceanospirillum beijerinckii (O. beijerinckii
      subsp. beijerinckii and O. beijerinckii subsp. pelagicum) should be combined as
      Oceanospirillum maris and Oceanospirillum beijerinckii, respectively.

PMID- 12054234
TI  - Transfer of Tsukamurella wratislaviensis Goodfellow et a. 1995 to the genus
      Rhodococcus as Rhodococcus wratislaviensis comb. nov..
AB  - A polyphasic study was undertaken to clarify the taxonomic position of the type
      strain (N805T) of Tsukamurella wratislaviensis. This organism showed a
      combination of phenotypic properties, notably chemotaxonomic markers, consistent
      with its classification in the genus Rhodococcus. Comparative 16S rDNA sequencing
      studies indicated that strain 805T falls into the Rhodococcus erythropolis
      subclade, where it forms a monophyletic group with the type strains of
      Rhodococcus opacus and Rhodococcus percolatus. The close relationship between
      these strains was underpinned by the results of mycolic acid analyses. However,
      strain N805T was distinguished from the R. opacus and R. percolatus strains in
      DNA-DNA pairing experiments and by using a range of phenotypic properties. In
      light of these studies, it is clear that strain N805T is misclassified in the
      genus Tsukamurella. It is, therefore, proposed that Tsukamurella wratislaviensis
      Goodfellow et al. 1995 be transferred to the genus Rhodococcus as Rhodococcus
      wratislaviensis comb. nov..

PMID- 12054235
TI  - Differences in rDNA libraries of faecal bacteria derived from 10- and 25-cycle
      PCRs.
AB  - In spite of its shortcoming, analysis of PCR-derived rDNA libraries is being
      employed increasingly to investigate microbial diversity within many ecosystems.
      In the present investigation, the effects of the number of PCR cycles (10 vs 25
      cycles) on the inferred structure of a 16S rDNA library have been examined.
      Seventy-five 25-cycle sequences were retrieved and analysed in comparison with
      284 10-cycle sequences already described in a previous study. The 359 clones
      obtained were classified into 94 molecular species (at least 98% sequence
      similarity). At the level of large phylogenetic groups, the two cloned rDNA
      libraries were not different. A mathematical model was developed in order to
      estimate the number of molecular species expected if further sequencing was
      performed. Coverage-based computing, projections and statistical analysis
      demonstrated that the structures of the two PCR-derived rDNA libraries were
      different and that the 25-cycle rDNA library displayed reduced diversity. It is
      suggested that the number of PCR cycles used for amplification of 16S rDNA genes
      for phylogenetic diversity studies must therefore be kept as small as possible.

PMID- 12054236
TI  - Thermodesulfobacterium hydrogeniphilum sp. nov., a thermophilic,
      chemolithoautotrophic, sulfate-reducing bacterium isolated from a deep-sea
      hydrothermal vent at Guaymas Basin, and emendation of the genus
      Thermodesulfobacterium.
AB  - A thermophilic, non-spore-forming, marine, sulfate-reducing bacterium, strain
      SL6T, was isolated from deep-sea hydrothermal sulfides collected at Guaymas
      Basin. The gram-negative-staining cells occurred singly or in pairs as small,
      highly motile rods. The temperature range for growth was 50-80 degrees C with an
      optimum at 75 degrees C. The pH range for growth at 70 degrees C was 6.3-6.8,
      with an optimum at 6.5. The NaCl concentration range for growth was 5-55 g l(-1),
      with an optimum at 30 g l(-1). H2 and CO2 were the only substrates for growth and
      sulfate reduction. However, growth was stimulated by several organic compounds.
      Sulfur, thiosulfate, sulfite, cystine, nitrate and fumarate were not used as
      electron acceptors. Pyruvate, lactate and malate did not support fermentative
      growth. Desulfoviridin was not detected. The G+C content of the genomic DNA was
      28 mol%. On the basis of 16S rRNA sequence analysis, strain SL6T is related to
      members of the genus Thermodesulfobacterium. However, the novel organism
      possesses phenotypic and phylogenetic traits that differ from those of its
      closest relatives. Therefore, it is proposed that this isolate, which constitutes
      the first marine representative of this genus, should be described as the type
      strain of a novel species, Thermodesulfobacterium hydrogeniphilum sp. nov. The
      type strain is SL6T (= DSM 14290T = JCM 11239T). Because of the phenotypic
      characteristics of the novel species, it is also proposed that the description of
      the genus Thermodesulfobacterium requires emendation.

PMID- 12054237
TI  - Methylobacterium suomiense sp. nov. and Methylobacterium lusitanum sp. nov.,
      aerobic, pink-pigmented, facultatively methylotrophic bacteria.
AB  - Two aerobic, pink-pigmented, facultatively methylotrophic bacteria, strains F20T
      and RXM(T), are described taxonomically. On the basis of their phenotypic and
      genotypic properties, the isolates are proposed as novel species of the genus
      Methylobacterium, Methylobacterium suomiense sp. nov. (type strain F20T = VKM B
      2238T = NCIMB 13778T) and Methylobacterium lusitanum sp. nov. (type strain RXMT =
      VKM B-2239T = NCIMB 13779T).

PMID- 12054238
TI  - Distributional profiles of homologous open reading frames among bacterial phyla:
      implications for vertical and lateral transmission.
AB  - If open reading frames (ORFs) have been transmitted primarily by vertical
      descent, the distributional profile of orthologues of each ORF should be
      congruent with the organismal tree or a subtree thereof. Distributional patterns
      not reconciled parsimoniously with tree-like descent and loss are prima facie
      evidence of lateral gene transfer. Herein, a rigorous criterion for recognizing
      ORF distributions is described and implemented; it does not require the inference
      of phylogenetic trees, nor does it assume any specific tree. Because lineage
      specific differences in rates of sequence change can also generate unexpected
      distributional patterns, rate artefacts were controlled for by requiring pairwise
      matches between ORFs to exceed a rigorous inclusion threshold, but absence of a
      match was assessed against a more-permissive exclusion threshold. Applying this
      dual-threshold criterion to cross-domain and cross-phylum distributional patterns
      for ORFs in 23 bacterial genomes, a relative abundance of ORFs was observed that
      find a match in exactly seven other bacterial phyla; 94-99% of these ORFs also
      find matches among the Archaea and/or Eukarya. In the larger (and some smaller)
      bacterial genomes, ORFs that find matches in exactly one other bacterial phylum
      are also relatively abundant, but fewer of these have non-bacterial homologues;
      most of their matches within the Bacteria are to the Proteobacteria and/or
      Firmicutes, which cannot be sister lineages to all bacteria. ORFs that are
      neither distributed universally among the Bacteria, nor necessarily shared with
      topologically adjacent lineages, are preferentially enriched in large bacterial
      genomes.

PMID- 12054239
TI  - Salinicoccus alkaliphilus sp. nov., a novel alkaliphile and moderate halophile
      from Baer Soda Lake in Inner Mongolia Autonomous Region, China.
AB  - A novel alkaliphilic and moderately halophilic gram-positive coccus, designated
      strain T8T, was isolated from Baer Soda Lake in Inner Mongolia Autonomous Region,
      China. Strain T8T grew in the presence of 0-25% (w/v) NaCl and at pH 6.5-11.5,
      with optimum growth at 10% (w/v) NaCl and pH 9.0. It grew at 10.0-46.0 degrees C,
      with an optimum growth temperature of 32.0 degrees C. The organism was strictly
      aerobic, non-motile, non-sporulating and catalase- and oxidase-positive. The DNA
      G+C content was 49.6 mol%. The cell wall contained Lys and Gly. The major
      isoprenoid quinone was menaquinone 6 (MK-6). Phylogenetic analyses based on 16S
      rDNA sequence comparisons indicate that strain T8T is a member of the genus
      Salinicoccus. DNA-DNA relatedness of less than 50% with the described species of
      Salinicoccus supported the view that this organism represents a novel species of
      the genus Salinicoccus. The name Salinicoccus alkaliphilus sp. nov. is proposed
      for this novel species. The type strain is T8T (= AS 1.2691T = JCM 11311T).

PMID- 12054240
TI  - Thermaerobacter subterraneus sp. nov., a novel aerobic bacterium from the Great
      Artesian Basin of Australia, and emendation of the genus Thermaerobacter.
AB  - A strictly aerobic, thermophilic, gram-positive, spore-producing, rod-shaped
      bacterium (2.0-10.0 x 0.3 microm), designated isolate C21T, was isolated from a
      sample collected from an open drain run-off channel of a bore in the Great
      Artesian Basin of Australia (New Lorne Bore, registered number 17263). Isolate
      C21T grew optimally at 70 degrees C (temperature range for growth was 55-80
      degrees C) and pH 8.5 (pH range for growth was 6.0-10.5), with a generation time
      of 90 min. The isolate was strictly heterotrophic and grew on yeast extract
      and/or tryptone as carbon and energy sources. An increase in growth was not
      observed with carbohydrates (sucrose, cellobiose, glucose, dextrin, amylopectin,
      chitin, carboxymethylcellulose, xylan, inositol, arabinose, mannose, fructose,
      gelatin, starch, amylose, galactose, dextrose, xylose, maltose, L-sorbose or
      raffinose), organic acids (lactic acid, pyruvic acid or benzoic acid) or Casamino
      acids as sole carbon sources or in the presence of yeast extract and/or tryptone.
      The G+C content of the chromosomal DNA, as measured by the thermal denaturation
      method, was 71 mol%. Phylogenetic analysis of the 16S rRNA gene of isolate C21T
      placed it as a member of the phylum Firmicutes, with Thermaerobacter marianensis
      as the closest relative (similarity value of 98%). However, isolate C21T and T.
      marianensis differed in a number of key physiological and phenotypic properties
      and also had a DNA-DNA hybridization value of less than 5%. Based on this
      evidence, it is proposed that strain C21T be designated Thermaerobacter
      subterraneus sp. nov. (type strain C21T = ATCC BAA-137T = DSM 13965T).

PMID- 12054241
TI  - Reclassification of Clostridium hydroxybenzoicum as Sedimentibacter
      hydroxybenzoicus gen. nov., comb. nov., and description of Sedimentibacter
      saalensis sp. nov..
AB  - Strain ZF2T, isolated from freshwater sediment, is a motile, rod-shaped, gram
      positive, endospore-forming, amino acid- and pyruvate-utilizing, anaerobic
      bacterium. It requires yeast extract for growth. Carbohydrates are not utilized.
      The optimal temperature and pH for growth are 37 degrees C and 6.8-7.3,
      respectively. The G+C content of the DNA is 34.0 mol %. A 16S rDNA sequence
      analysis of strain ZF2T revealed that the highest similarity (94.4%) was shared
      with Clostridium hydroxybenzoicum JW/Z-1T. Strain ZF2T, however, was not able to
      carboxylate phenol or to decarboxylate 4-hydroxybenzoate, which are
      characteristic properties of strain JW/Z-1T. The degree of 16S rDNA relatedness,
      together with the physiological and chemotaxonomic properties, suggest that
      strain ZF2T represents a novel species that is clearly distinct from Clostridium
      hydroxybenzoicum JW/Z-1T. In a phylogenetic dendrogram, both strains form a
      separate cluster that is peripherally associated with the Peptostreptococcus
      group (cluster XIII) of the clostridia and the lineage of Helcococcus kunzii.
      Strains ZF2T and JW/Z-1T show a somewhat deeper branching from the cluster XII
      clostridia Clostridium purinolyticum and Clostridium acidiurici. The latter
      strains possessed the closest 16S rDNA similarity (between 88.4 and 90.7%), but
      were clearly separated by phenotypic markers. Therefore, a new genus,
      Sedimentibacter gen. nov., is described, comprising Sedimentibacter
      hydroxybenzoicus gen. nov., comb. nov., as the type species of the genus, with
      JW/Z-1T (= ATCC 51151T = DSM 7310T) as the type strain, and the novel species
      Sedimentibacter saalensis sp. nov., with strain ZF2T (= DSM 13558T = ATCC BAA
      283T) as the type strain.

PMID- 12054242
TI  - Transfer of Bifidobacterium inopinatum and Bifidobacterium denticolens to
      Scardovia inopinata gen. nov., comb. nov., and Parascardovia denticolens gen.
      nov., comb. nov., respectively.
AB  - Bifidobacterium inopinatum Crociani et al. 1996 and Bifidobacterium denticolens
      Crociani et al. 1996 have distinct phenotypic characteristics and low G+C
      contents compared with other bifidobacteria. In the 16S rRNA phylogenetic tree,
      these two species grouped in an independent subcluster. In our previous work,
      partial heat-shock protein 60 (HSP60) gene-sequence analysis also indicated that
      these two species had distinct taxonomic positions. In this work, the complete
      HSP60 genes of five representative bacterial strains were sequenced by using an
      inverse PCR method. The complete sequence similarities turned out to be at the
      same level as those of the partial genes, thus confirming the result based on
      partial sequence analysis. On the basis of all the evidence mentioned above, it
      is proposed that these two species should be transferred to two new genera as
      Scardovia inopinata gen. nov., comb. nov., and Parascardovia denticolens gen.
      nov., comb. nov.

PMID- 12054243
TI  - Kozakia baliensis gen. nov., sp. nov., a novel acetic acid bacterium in the alpha
      proteobacteria.
AB  - Four bacterial strains were isolated from palm brown sugar and ragi collected in
      Bali and Yogyakarta, Indonesia, by an enrichment culture approach for acetic acid
      bacteria. Phylogenetic analysis based on 16S rRNA gene sequences showed that the
      four isolates constituted a cluster separate from the genera Acetobacter,
      Gluconobacter, Acidomonas, Gluconacetobacter and Asaia with a high bootstrap
      value in a phylogenetic tree. The isolates had high values of DNA-DNA similarity
      (78-100%) between one another and low values of the similarity (7-25%) to the
      type strains of Acetobacter aceti, Gluconobacter oxydans, Gluconacetobacter
      liquefaciens and Asaia bogorensis. The DNA base composition of the isolates
      ranged from 56.8 to 57.2 mol% G+C with a range of 0-4 mol%. The major quinone was
      Q-10. The isolates oxidized acetate and lactate to carbon dioxide and water, but
      the activity was weak, as with strains of Asaia bogorensis. The isolates differed
      from Asaia bogorensis strains in phenotypic characteristics. The name Kozakia
      baliensis gen. nov., sp. nov., is proposed for the four isolates. Strain Yo-3T (=
      NRIC 0488T = JCM 11301T = IFO 16664T = DSM 14400T) was isolated from palm brown
      sugar collected in Bali, Indonesia, and was designated as the type strain.

PMID- 12054244
TI  - Description of Methanobrevibacter gottschalkii sp. nov., Methanobrevibacter
      thaueri sp. nov., Methanobrevibacter woesei sp. nov. and Methanobrevibacter
      wolinii sp. nov..
AB  - Formal nomenclature is proposed for five methanogens, isolated from horse, pig,
      cow, goose and sheep faeces, that represent four novel species of the genus
      Methanobrevibacter. The four species, Methanobrevibacter gottschalkii sp. nov.,
      Methanobrevibacter thaueri sp. nov., Methanobrevibacter woesei sp. nov. and
      Methanobrevibacter wolinii sp. nov., are distinguished from each other by a lack
      of genomic DNA reassociation and from previously described members of the genus
      on the basis of differences in the sequences of the 16S rRNA genes.

PMID- 12054245
TI  - The search for synonyms among streptomycetes by using SDS-PAGE of whole-cell
      proteins. Emendation of the species Streptomyces aurantiacus, Streptomyces cacaoi
      subsp. cacaoi, Streptomyces caeruleus and Streptomyces violaceus.
AB  - A collection of 93 Streptomyces reference strains were investigated using SDS
      PAGE of whole-cell proteins. Computer-assisted numerical analysis revealed 24
      clusters encompassing strains with very similar protein profiles. Five of them
      grouped several type strains with visually identical patterns. DNA-DNA
      hybridizations revealed homology values higher than 70% among these type strains.
      According to the current species concept, it is proposed that Streptomyces
      albosporeus subsp. albosporeus LMG 19403T is considered as a subjective synonym
      of Streptomyces aurantiacus LMG 19358T, that Streptomyces aminophilus LMG 19319T
      is considered as a subjective synonym of Streptomyces cacaoi subsp. cacaoi LMG
      19320T, that Streptomyces niveus LMG 19395T and Streptomyces spheroides LMG
      19392T are considered as subjective synonyms of Streptomyces caeruleus LMG
      19399T, and that Streptomyces violatus LMG 19397T is considered as a subjective
      synonym of Streptomyces violaceus LMG 19360T.

PMID- 12054246
TI  - Weissella soli sp. nov., a lactic acid bacterium isolated from soil.
AB  - Phylogenetic analysis of the 16S rRNA gene of bacterial isolates from garden soil
      showed relatedness to Weissella kandleri and Weissella confusa. However, the
      sequences had notable differences, and DNA-DNA hybridizations confirmed that the
      isolates are separate from these two species. The isolates could be further
      distinguished from all previously described Weissella species by electrophoretic
      analysis of whole-cell proteins, as well as by the results from different
      biochemical tests. The name Weissella soli is proposed for the new species, the
      type strain being Mi268T (= LMG 20113T = DSM 14420T).

PMID- 12054247
TI  - Chelatobacter heintzii (Auling et al. 1993) is a later subjective synonym of
      Aminobacter aminovorans (Urakami et al. 1992).
AB  - Chelatobacter heintzii, which was described as a nitrilotriacetate-utilizing
      organism, was re-investigated in order to clarify its taxonomic position. On the
      basis of 16S rDNA sequence comparisons, it is obvious that this species clusters
      phylogenetically with species of the genus Aminobacter. The results of
      investigations of the fatty acid patterns, polar lipid profiles, polyamine
      patterns and quinone system supported this placement. The substrate-utilization
      profiles and fatty acid patterns of four strains (belonging to two different
      genomovars) revealed homogeneous results and showed high levels of similarity to
      Aminobacter aminovorans. DNA-DNA similarity studies confirmed that both
      genomovars of Chelatobacter heintzii belong to Aminobacter aminovorans. It could
      be shown that all species of this group are highly interrelated. On the basis of
      these data and previously published results, it is obvious that Chelatobacter
      heintzii is a later subjective synonym of Aminobacter aminovorans.

PMID- 12054248
TI  - Reclassification of Bacteroides forsythus (Tanner et al. 1986) as Tannerella
      forsythensis corrig., gen. nov., comb. nov.
AB  - The characteristics of the fusiform species Bacteroides forsythus, isolated from
      human periodontal pockets, were examined. 165 rDNA sequence analysis confirmed
      that B. forsythus was not a species within the genus Bacteroides sensu stricto.
      Although B. forsythus was phylogenetically related to Bacteroides distasonis and
      Bacteroides merdae in the phylogenetic tree, the ratio of anteiso-15:0 to iso
      15:0 in whole-cell methanolysates of B. forsythus was different from those of B.
      distasonis, B. merdae and other Bacteroides species. B. forsythus did not grow on
      medium containing 20% bile, but members of the Bacteroides fragilis group did. B.
      forsythus was the only species tested that was trypsin-positive in API ZYM tests.
      The dehydrogenase enzyme pattern was of no use for the differentiation of B.
      forsythus and the B. fragilis group. On the basis of these data, a new genus,
      Tannerella, is proposed for Bacteroides forsythus, with one species, Tannerella
      forsythensis corrig., gen. nov., comb. nov. The type strain of Tannerella
      forsythensis is JCM 10827T (= ATCC 43037T).

PMID- 12054249
TI  - Leisingera methylohalidivorans gen. nov., sp. nov., a marine methylotroph that
      grows on methyl bromide.
AB  - A marine methylotroph, designated strain MB2T, was isolated for its ability to
      grow on methyl bromide as a sole carbon and energy source. Methyl chloride and
      methyl iodide also supported growth, as did methionine and glycine betaine. A
      limited amount of growth was observed with dimethyl sulfide. Growth was also
      noted with unidentified components of the complex media marine broth 2216, yeast
      extract and Casamino acids. No growth was observed on methylated amines,
      methanol, formate, acetate, glucose or a variety of other substrates. Growth on
      methyl bromide and methyl iodide resulted in their oxidation to CO2 with
      stoichiometric release of bromide and iodide, respectively. Strain MB2T exhibited
      growth optima at NaCl and Mg2+ concentrations similar to that of seawater.
      Phylogenetic analysis of the 16S rDNA sequence placed this strain in the alpha
      Proteobacteria in proximity to the genera Ruegeria and Roseobacter. It is
      proposed that strain MB2T (= ATCC BAA-92T = DSM 14336T) be designated Leisingera
      methylohalidivorans gen. nov., sp. nov..

PMID- 12054250
TI  - The cpcB-cpcA locus as a tool for the genetic characterization of the genus
      Arthrospira (Cyanobacteria): evidence for horizontal transfer.
AB  - To investigate the genetic diversity of the genus Arthrospira and to compare it
      with other cyanobacteria, sequences of 670 nt from the phycocyanin operon were
      determined for 23 natural, cultivated or commercial strains of Arthrospira and
      compared with sequences from 20 other non-Arthrospira cyanobacterial strains. The
      sequenced DNA fragment comprises the last 255 nt of cpcB, the cpcB-cpcA spacer
      and the first 304 nt of cpcA. The resulting phylogenetic tree confirms that the
      genus Arthrospira is not related to Spirulina. So far, cpcB-cpcA data suggest
      that the closest relative of Arthrospira is Planktothrix. Based on this locus,
      the genus Arthrospira consists of three genetically clustered lineages. However,
      the distribution of nucleotide substitutions indicates that these three lineages
      are not the result of a simple cladogenesis characterized by the accumulation of
      independent substitutions. Instead, the observed clustering is the result of
      horizontal transfers of blocks of sequences. Analysis of the distribution of
      substitutions in the sequenced fragment indicates a point of intragenic
      recombination close to the stop codon of cpcB. The capacity of exchange of
      genetic material among strains probably explains why morphology and geographical
      origin do not correlate with the cpcB-cpcA clusters. Nevertheless, this study
      shows for the first time that the genus Arthrospira, represented here by
      cultivated and wild specimens, is clearly monophyletic. Moreover, the cpcB-cpcA
      DNA fragment, comprising both highly and moderately variable regions, allows (1)
      a strict differentiation of the taxon Arthrospira from other cyanobacteria (using
      the coding regions only) and (2) the study of relationships inside Arthrospira
      (using both the coding and non-coding regions).

PMID- 12054251
TI  - Bacillus subterraneus sp. nov., an iron- and manganese-reducing bacterium from a
      deep subsurface Australian thermal aquifer.
AB  - A facultatively anaerobic bacterium, designated strain COOI3B(T) (= ATCC BAA 136T
      = DSM 13966T), was isolated from the waters emitted by a bore well tapping the
      deep subterranean thermal waters of the Great Artesian Basin of Australia. The
      cells were straight to slightly curved rods (0.5-0.8 x 2-25 microm) that occurred
      singly and rarely in pairs or in chains. Strain COOI3B(T) was motile by
      peritrichous flagella. It stained gram-negative, but electron micrographs showed
      a gram-positive-type cell wall. Spores were never observed and cells were heat
      sensitive. Yeast extract at 0.02% (w/v) was required for growth and could also be
      used as a sole carbon and energy source at concentrations higher than 0.1% (w/v).
      The strain utilized amorphous iron(III), manganese(IV), nitrate, nitrite and
      fumarate as electron acceptors in the presence of yeast extract, glucose,
      sucrose, fructose, maltose, xylose, starch, glycerol, ethanol or lactate.
      Electron acceptors were not obligately required and growth was better in the
      presence of nitrate than in its absence. Acid was not produced from growth on
      carbohydrates. Tryptophan deaminase, H2S, arginine dihydrolase, lysine
      decarboxylase, beta-galactosidase, arabinosidase, glucuronidase, glucosaminidase,
      nitroanilidase, xylosidase and ornithine decarboxylase were not produced. Starch
      and gelatin, but not casein, were hydrolysed. Aesculin and catalase, but not
      oxidase and urease, were produced. Strain COOI3B(T) grew optimally at
      temperatures between 37 and 40 degrees C (the temperature growth range was 25-45
      degrees C) and at pH 7.0-9.0 (the pH growth range was 6.0 to 9.5) with 5% (w/v)
      NaCl (the NaCl concentration growth range was 0.9%, w/v). The DNA base
      composition was 43 +/- 1 mol % G+C. Phylogenetic analysis indicated that it was a
      member of the family Bacillaceae, Bacillus infernus and Bacillus firmus being the
      closest phylogenetic neighbours (having a mean similarity value of 96%); hence,
      strain COOI3B(T) is designated as a novel species, Bacillus subterraneus sp. nov.

PMID- 12054252
TI  - Georgenia muralis gen. nov., sp. nov., a novel actinobacterium isolated from a
      medieval wall painting.
AB  - Two bacterial strains, designated 1A-C(T) and 3A-1, were studied and, using these
      results and previously published data, taxonomically classified. Cells of the
      strains exhibited a rod-coccus cycle. The peptidoglycan determined for 1A-C(T)
      was of type A4alpha with lysine as the diagnostic cell-wall diamino acid and an
      interpeptide bridge of L-Lys <-- L-Glu. The menaquinone systems of the two
      strains contained MK-8(H4) (82-94%) and MK-7(H4) (3-11%). The polar lipid
      profiles consisted of diphosphatidylglycerol, phosphatidylglycerol,
      phosphatidylinositol mannoside, two unidentified phospholipids and an
      unidentified glycolipid. The fatty acid profiles contained predominantly ai-C15:0
      and significant amounts of i-C14:0 and i-C15:1 fatty acids. Genomic fingerprints
      clearly distinguished strains 1A-C(T) and 3A-1 from each other. DNA-DNA
      relatedness between the two strains (92%) demonstrated that they are members of a
      single species. Analyses of the 16S rDNA sequences of strains IA-C(T) and 3A-1,
      which were almost identical (99.6% sequence similarity), and comparison with
      corresponding sequences demonstrated that they represent a novel lineage within
      the suborder Micrococcineae, most closely related to species of the genera
      Beutenbergia, Bogoriella and Cellulomonas (94.7-95.7% sequence similarity). The
      results demonstrate that the two strains are members of a single new genus and a
      single novel species. Thus, the name Georgenia muralis gen. nov., sp. nov. is
      proposed. The type strain is strain 1A-C(T) (= DSM 14418T = CCM 4963T). Another
      strain of the species is strain 3A-1 (= DSM 14419 = CCM 4964).

PMID- 12054253
TI  - Tetrasphaera elongata sp. nov., a polyphosphate-accumulating bacterium isolated
      from activated sludge.
AB  - A new meso-diaminopimelic acid-containing, gram-positive bacterium was isolated
      from an activated sludge reactor showing enhanced biological phosphorus removal
      activity. The isolate was an asporogenous oval to rod-shaped bacterium, but
      occasionally formed clumps. The Neisser staining was positive, suggesting
      intracellular polyphosphate granules. The isolate was an aerobic chemoheterotroph
      which was capable of utilizing various sugars, sugar alcohols and organic acids.
      It contained anteiso-C15:0, iso-C15:0, iso-C14:0 and C16:0 as the major cellular
      fatty acids, and menaquinone-8(H4) as the major quinone. The G+C content of the
      genomic DNA was 69.6 mol%. Analysis of the 16S rDNA sequence revealed that the
      isolate is a new member of the family Intrasporangiaceae. The closest relatives
      were Tetrasphaera species. On the basis of the phenotypic and phylogenetic
      distinctiveness of the isolate, it was concluded that the organism represents a
      new species in the genus Tetrasphaera, for which the name Tetrasphaera elongata
      sp. nov. is proposed. The type strain is strain Lp2T (= JCM 11141T = DSM 14184T).

PMID- 12054254
TI  - Amycolatopsis eurytherma sp. nov., a thermophilic actinomycete isolated from
      soil.
AB  - The taxonomic positions of two thermophilic actinomycetes isolated from soil were
      established in a polyphasic taxonomic study. The organisms were shown to have
      phenotypic properties typical of members of the genus Amycolatopsis and formed a
      distinct phyletic line in the Amycolatopsis methanolica 16S rDNA subclade. They
      also had many phenotypic properties in common and formed a genomic species that
      was closely related to, albeit distinct from, the type strain of A. methanolica.
      A range of phenotypic properties distinguished the isolates from representatives
      of all validly described species of Amycolatopsis. Genotypic and phenotypic data
      show that the two strains should be classified in the genus Amycolatopsis as a
      novel species, Amycolatopsis eurytherma sp. nov.; the type strain is strain
      NT202T (= DSM 44348T = NCIMB 13795T).

PMID- 12054255
TI  - Caldimonas manganoxidans gen. nov., sp. nov., a poly(3-hydroxybutyrate)
      degrading, manganese-oxidizing thermophile.
AB  - A poly(3-hydroxybutyrate) (PHB)-degrading, gram-negative, aerobic bacterium,
      strain HS(T), was isolated from a hot spring and chemotaxonomically and
      phylogenetically characterized. The oxidase-positive, weakly catalase-positive,
      non-pigmented cells (0.6 x 2.6 microm) exhibited a single polar flagellum and
      accumulated PHB granules. Strain HS(T) was capable of manganese oxidation.
      Highest growth rate was attained at 50 degrees C. The optimum pH for growth was 7
      8. The major respiratory quinone was ubiquinone-8 and major cellular fatty acids
      were C16:0, C16:1 and C18:1. The G+C content of the DNA was 66.2 mol%.
      Comparative 16S rDNA analysis indicated that strain HS(T) is related to the
      Rubrivivax subgroup and the family Comamonadaceae. The nearest phylogenetic
      relatives were Ideonella dechloratans (92.1% similarity), Leptothrix discophora
      (93.6%), Roseateles depolymerans (92.4%) and Rubrivivax gelatinosus (92.2%). On
      the basis of its phylogenetic and phenotypic properties, it is proposed that this
      isolate be designated Caldimonas manganoxidans gen. nov., sp. nov.; the type
      strain is HS(T) (= JCM 10698T = IFO 16448T = ATCC BAA-369T).

PMID- 12054256
TI  - Oleiphilaceae fam. nov., to include Oleiphilus messinensis gen. nov., sp. nov., a
      novel marine bacterium that obligately utilizes hydrocarbons.
AB  - A bacterial isolate, ME102T, was obtained from an n-hexadecane enrichment culture
      of seawater/sediment samples collected in the harbour of Messina (Italy). This
      gram-negative, aerobic, motile, rod-shaped bacterium used a narrow spectrum of
      organic compounds, including aliphatic hydrocarbons, alkanoates and alkanoles, as
      carbon and energy sources. None of the sugars, organic acids or amino acids
      tested was used. During cultivation on n-alkanes as the sole source of carbon and
      energy, the cells formed a biofilm on the surface of the alkane droplets. Large
      scale (sometimes >50% of the cell mass) intracellular accumulation of alkanoates
      occurred in cells adsorbed on the alkane surface and under nitrogen-limiting
      conditions. 16S rRNA gene sequence analysis showed that this isolate represents a
      distinct lineage in the gamma-Proteobacteria and has about 91% sequence identity
      to members of Marinobacter and Alcanivorax, the closest genera. Four different
      types of polar lipid could be detected, phosphatidyl glycerol, phosphatidyl
      ethylamine, phosphatidyl dimethylethylamine and lipids belonging to an unknown
      type of phospholipid (m/z between 861 and 879). The principal fatty acids in the
      polar lipid fatty acid profile were 16:0 and 16:1. The putative gene encoding the
      key enzyme of alkane catabolism, alkane hydroxylase (AlkB), has been cloned. The
      protein sequence of the putative AlkB of the isolate ME102T was related to the
      AlkB of Pseudomonas oleovorans and Alcanivorax borkumensis, showing about 60%
      sequence identity. On the basis of physiological studies and taking into account
      the distant phylogenetic position of isolate ME102T relative to previously
      described organisms, a novel genus and species is proposed, Oleiphilus
      messinensis gen. nov., sp. nov., within a new family, Oleiphilaceae fam. nov.
      Strain ME102T (= DSM 13489T = LMG 20357T) is the type and only strain of O.
      messinensis.

PMID- 12054257
TI  - Thioalkalimicrobium cyclicum sp. nov. and Thioalkalivibrio jannaschii sp. nov.,
      novel species of haloalkaliphilic, obligately chemolithoautotrophic sulfur
      oxidizing bacteria from hypersaline alkaline Mono Lake (California).
AB  - Two strains of haloalkaliphilic, obligately autotrophic, sulfur-oxidizing
      bacteria were isolated from the oxygen-sulfide interface water layer of
      stratified alkaline and saline Mono Lake, California, USA. Strain ALM 1T was a
      dominant species in enrichment on moderate-saline, carbonate-buffered medium (0.6
      M total Na+, pH 10) with thiosulfate as an energy source and nitrate as a
      nitrogen source. Cells of ALM 1T are open ring-shaped and are non-motile. It has
      a high growth rate and activity of thiosulfate and sulfide oxidation and very low
      sulfur-oxidizing activity. Genetic comparison and phylogenetic analysis suggested
      that ALM 1T (= DSM 14477T = JCM 11371T) represents a new species of the genus
      Thioalkalimicrobium in the gamma-Proteobacteria, for which the name
      Thioalkalimicrobium cyclicum sp. nov. is proposed. Another Mono Lake isolate,
      strain ALM 2T, dominated in enrichment on a medium containing 2 M total Na+ (pH
      10). It is a motile vibrio which tolerates up to 4 M Na+ and produces a membrane
      bound yellow pigment. Phylogenetic analysis placed ALM 2T as a member of genus
      Thioalkalivibrio in the gamma-Proteobacteria, although its DNA hybridization with
      the representative strains of this genus was only about 30%. On the basis of
      genetic and phenotypic properties, strain ALM 2T (= DSM 14478T = JCM 11372T) is
      proposed as Thioalkalivibrio jannaschii sp. nov..

PMID- 12054258
TI  - Clostridium lactatifermen tans sp. nov., a lactate-fermenting anaerobe isolated
      from the caeca of a chicken.
AB  - An obligately anaerobic, lactate-fermenting bacterium (strain G17T) was isolated
      from the caeca of a 31-day-old chicken. Grown at neutral pH, cells were rod
      shaped with tapered ends and showed no motility and no spore formation. Electron
      microscopy showed that the cell walls had a gram-positive structure. The DNA G+C
      content was 44.6 mol %. Based on 16S rDNA sequence analysis, strain G17T was
      considered to belong to the low-G+C-content gram-positive bacteria of cluster XIV
      subgroup b and most closely related to Clostridium propionicum (93.5%) and
      Clostridium neopropionicum (93.5%). The optimum temperature for growth was 41
      degrees C and the optimum pH was pH 6.4-7.3. The optimum temperature of 41
      degrees C suggests that strain G17T might have become adapted to the body
      temperature of chickens. Strain G17T was able to grow on a variety of organic
      compounds. Most of these compounds were converted to acetate, propionate and
      traces of butyrate and isovalerate. In media with mixtures of substrates, lactate
      was degraded by strain G17T before the other substrates. This indicates that
      strain G17T might be important in the fermentation of lactate in the caeca of
      chickens. Based on its physiological and phylogenetic characteristics, it is
      proposed that strain G17T should be assigned to the genus Clostridium as a novel
      species, Clostridium lactatifermentans sp. nov.

PMID- 12054259
TI  - Lactobacillus durianis sp. nov., isolated from an acid-fermented condiment
      (tempoyak) in Malaysia.
AB  - Lactic acid bacteria (LAB) are the predominant micro-organisms in tempoyak, a
      Malaysian acid-fermented condiment. In a study on the diversity of LAB in this
      product, three isolates could not be identified using SDS-PAGE of whole-cell
      proteins or API 50 CH. The taxonomic position of the three isolates was clarified
      in the present study. 16S rDNA sequencing classified a representative strain in
      the genus Lactobacillus, clearly separated from all known species, and most
      closely related to the Lactobacillus reuteri phylogenetic group. DNA-DNA
      hybridization experiments and an extensive phenotypic description confirm that
      the strains represent a single and separate novel species among the obligately
      heterofermentative lactobacilli. The three isolates are distinguished at the
      intra-species level by plasmid profiling, pulsed-field gel electrophoresis of
      macro-restriction fragments and biochemical features. The name Lactobacillus
      durianis sp. nov. is proposed for the novel taxon and the type strain is LMG
      19193T (= CCUG 45405T).

PMID- 12054260
TI  - Kineococcus radiotolerans sp. nov., a radiation-resistant, gram-positive
      bacterium.
AB  - A gram-type positive, motile, coccus-shaped organism was isolated from a
      radioactive work area. Strain SRS30216T is an orange-pigmented bacterium that is
      catalase-positive, oxidase-negative and urease-negative. The orange pigment is
      most likely a carotenoid with absorption peaks at approximately 444, 471 and 501
      nm. Cells normally grew in clusters, but individual, motile, flagellated cells
      were also observed. Growth of strain SRS30216T occurred at temperatures between
      11 and 41 degrees C, between pH 5 and 9 and at NaCl concentrations up to and
      including 5%. Fatty acid composition was limited, with >90% of the fatty acids
      being anteiso 15:0. Alkenes of 19-24 carbons in length were detected during
      examination of the neutral lipids. Strain SRS30216T demonstrated high levels of
      resistance to gamma-radiation and desiccation. The most closely related
      recognized species is Kineococcus aurantiacus RA 333T, which is 93% similar in
      16S rDNA sequence. DNA-DNA hybridization revealed only 31% similarity between
      these two organisms. It is proposed that SRS30216T (= ATCC BAA-149T = DSM 14245T)
      represents the type strain of a novel species in the genus Kineococcus,
      Kineococcus radiotolerans sp. nov..

PMID- 12054262
TI  - Comparison between Streptococcus macedonicus and Streptococcus waius strains and
      reclassification of Streptococcus waius (Flint et at. 1999) as Streptococcus
      macedonicus (Tsakalidou et al. 1998).
AB  - Two species of dairy streptococci, Streptococcus waius and Streptococcus
      macedonicus, were originally characterized by 16S-23S intergenic spacer sequence
      analysis, random amplified polymorphic DNA fingerprinting, PFGE analysis and DNA
      DNA reassociation experiments. All genetic data suggested that S. waius strains
      belong to the previously described species S. macedonicus. Likewise, the
      phenotypic characterization showed that strains of S. macedonicus and S. waius
      were highly related and easily differentiated from the closest phylogenetic
      neighbour, Streptococcus bovis, principally by their failure to produce a
      blackening reaction in medium containing aesculin. The utilization of maltose and
      cellobiose by S. macedonicus/S. waius strains allowed their differentiation from
      the most studied dairy species, Streptococcus thermophilus. On the basis of
      genetic and phenotypic data S. macedonicus and S. waius species should be
      considered synonyms and S. macedonicus has the priority.

PMID- 12054261
TI  - Isolation from a shea cake digester of a tannin-degrading Streptococcus
      gallolyticus strain that decarboxylates protocatechuic and hydroxycinnamic acids,
      and emendation of the species.
AB  - A facultatively anaerobic, mesophilic, non-motile, non-sporulating bacterium,
      designated strain B7, was isolated from an anaerobic digester fed with shea cake
      rich in tannins and aromatic compounds, after enrichment on tannic acid. The
      coccoid cells (less than 2 microm in diameter) occurred in pairs or short chains
      and stained gram-positive. Strain B7 fermented a wide range of carbohydrates
      (cellobiose, fructose, galactose, glucose, lactose, maltose, mannitol, melibiose,
      raffinose and trehalose), grew optimally at pH 7.0 and had a G+C content of
      40.4+/-0.3 mol%. Strain B7 was closely related to Streptococcus gallolyticus ACM
      3611T, a member of the Streptococcus bovis rRNA cluster, with a sequence
      similarity of 98% and a DNA hybridization value of 86 mol%. Isolate B7 hydrolysed
      tannic acid and decarboxylated gallic acid to pyrogallol, traits also observed in
      S. gallolyticus ACM 3611T. In addition, both strains decarboxylated
      protocatechuic acid to catechol, p-coumaric acid to 4-vinylphenol, caffeic acid
      to 4-vinylcatechol and ferulic acid to 4-vinylguaiacol. An unsubstituted para
      hydroxyl group on the benzene ring was required for decarboxylation. Glucose
      addition markedly increased the conversion rate. As these traits were not
      described previously, emendation of the description of the species Streptococcus
      gallolyticus is proposed.

PMID- 12054263
TI  - Polyphasic identification of Bacillus and Brevibacillus strains from clinical,
      dairy and industrial specimens and proposal of Brevibacillus invocatus sp. nov..
AB  - Thirty-three clinical, dairy and industrial isolates of aerobic endospore-forming
      bacteria which were unreactive in routine identification tests were characterized
      genotypically by using amplified rDNA restriction analysis (ARDRA), 16S rDNA
      sequencing and DNA-DNA reassociation, and phenotypically by using fatty acid
      methyl ester (FAME) analysis, SDS-PAGE of whole-cell proteins, API Biotype 100
      assimilation tests and 16 other routine phenotypic tests. Three isolates were
      identified as strains of Bacillus badius, 12 as Brevibacillus agri, including 3
      strains associated with an outbreak of waterborne illness, 4 as Brevibacillus
      centrosporus and 2 as Brevibacillus parabrevis; 12 strains contaminating an
      antibiotic production plant were recognized as members of a new species, for
      which the name Brevibacillus invocatus is proposed, with the type strain LMG
      18962T (= B2156T = CIP 106911T = NCIMB 13772T).

PMID- 12054264
TI  - Proposal to transfer Catellatospora ferruginea and 'Catellatospora ishikariense'
      to Asanoa gen. nov. as Asanoa ferruginea comb. nov. and Asanoa ishikariensis sp.
      nov., with emended description of the genus Catellatospora.
AB  - The taxonomic position of Catellatospora ferruginea and 'Catellatospora
      ishikariense' was investigated by phylogenetic, chemotaxonomic and physiological
      characterization. The 16S rDNA sequences of the organisms were compared with
      those of members of the genus Catellatospora and other genera of the
      Micromonosporaceae and phylogenetic trees were inferred by using distance-matrix
      and parsimony methods. The organisms formed a distinct cluster within the
      radiation of this family that was supported by a high bootstrap value, of 100%.
      The nearest neighbours were members of the genera Catenuloplanes and
      Verrucosispora. The organisms were readily differentiated from all of the validly
      described genera of the family Micromonosporaceae by using a battery of chemical
      and morphological characters, and the name Asanoa gen. nov. is proposed. On the
      basis of phenotypic and DNA-DNA hybridization data, Asanoa ferruginea comb. nov.
      (type strain IMSNU 22009T = IFO 14496T DSM 44099T) and Asanoa ishikariensis sp.
      nov. (type strain IMSNU 22004T = IFO 14551T) are described.

PMID- 12054265
TI  - Vibrio trachuri Iwamoto et al. 1995 is a junior synonym of Vibrio harveyi
      (Johnson and Shunk 1936) Baumann et al. 1981.
AB  - The taxonomic position of Vibrio trachuri was examined through a polyphasic
      approach using 16S rDNA sequencing, fluorescent amplified fragment length
      polymorphisms (FAFLP), DNA-DNA hybridization experiments, G+C content of DNA and
      phenotypical tests. Phylogenetic analysis showed that Vibrio harveyi is the
      closest neighbour of V. trachuri, sharing about 98.8% similarity in the 16S rDNA
      gene. Moreover, numerical analysis of the FAFLP patterns revealed that both
      species have highly related genomes, sharing 55% pattern similarity. DNA-DNA
      hybridization experiments and G+C content measurements reinforced these results,
      since V. trachuri and V. harveyi had at least 74% DNA similarity and 44.5-45.2
      mol % G+C. Phenotypical features of both species were also very similar, except
      that V. trachuri utilized itaconic acid, whereas V. harveyi did not. Therefore,
      it is proposed that the species V. trachuri should be reclassified as V. harveyi.

PMID- 12054266
TI  - Proposal to combine the genera Actinobispora and Pseudonocardia in an emended
      genus Pseudonocardia, and description of Pseudonocardia zijingensis sp. nov..
AB  - The 16S rDNA sequences of four strains, i.e. three type strains of Actinobispora
      and strain 6330T, were determined and compared with those of representatives of
      the family Pseudonocardiaceae by using two tree-making algorithms. All the
      validly described species of the genera Actinobispora and Pseudonocardia were
      consistently recovered as a mixed group in phylogenetic trees, and were distinct
      from the other genera of the family Pseudonocardiaceae. Strain 6330T formed a
      distinct phyletic line in the 16S rDNA tree and was most closely associated with
      the type strain of Actinobispora aurantiaca. The use of specific PCR primers
      designed for differentiating the genus Pseudonocardia from other genera of the
      family Pseudonocardiaceae showed that all the Actinobispora species and strain
      6330T have the same amplified 640 bp 16S rDNA fragment as members of the genus
      Pseudonocardia. The DNA-DNA relatedness, chemotaxonomic and phenotypic data also
      supported classification of these taxa in the genus Pseudonocardia, and
      distinguished each from the others. On the basis of these observations, it is
      proposed that the genera Actinobispora and Pseudonocardia be combined in an
      emended genus Pseudonocardia, and that strain 6330T be classified in the same
      genus as Pseudonocardia zijingensis sp. nov. The type strain is 6330T (= AS
      4.1545T = JCM 11117T).

PMID- 12054267
TI  - Anaeroglobus geminatus gen. nov., sp. nov., a novel member of the family
      Veillonellaceae.
AB  - A hitherto unknown anaerobic coccus isolated from a post-operative fluid
      collection was characterized by phenotypic and phylogenetic methods. 16S rDNA
      sequence analysis revealed an affiliation of this isolate to the family
      Veillonellaceae. Also, a high level of sequence similarity was observed to some
      oral clone sequences of Megasphaera spp. contained in the GenBank database under
      designations BB166, CS025 and BS073. These clones and the unknown bacterium form
      a well-separated phylogenetic branch that may represent a novel lineage within
      the family Veillonellaceae. Based on phenotypic and phylogenetic evidence, a new
      genus, Anaeroglobus gen. nov., is proposed for the unknown bacterium, with one
      species, Anaeroglobus geminatus gen. nov., sp. nov. The type strain of
      Anaeroglobus geminatus is strain AIP 313.00T (= CIP 106856T = CCUG 44773T). It is
      also suggested that the oral clones BB166, CS025 and BS073 belong to the genus
      Anaeroglobus.

PMID- 12054268
TI  - Okibacterium fritillariae gen. nov., sp. nov., a novel genus of the family
      Microbacteriaceae.
AB  - Okibacterium fritillariae gen. nov., sp. nov. (type strain VKM Ac-2059T = IFO
      16404T) is proposed for aerobic, oxidase- and catalase-positive, coryneform
      bacteria isolated from seeds of Fritillaria ruthenica Wikstr. and Clematis recta
      L. Strains of the new genus form a distinct branch within the phylogenetic
      cluster composed of members of the family Microbacteriaceae and are characterized
      by B-type peptidoglycan containing amino acids glycine, glutamate, homoserine,
      alanine and lysine, the glycolyl type of muramic acid, the major menaquinones MK
      10 and MK-11, the principal phospholipids phosphatidylglycerol and
      diphosphatidylglycerol, and a DNA G+C content of approximately 67 mol %.

PMID- 12054270
TI  - Population aging and its impact on elderly welfare in Africa.
AB  - This article discusses the demographic transition and its impact on the welfare
      of the elderly in Africa. It provides a brief socio-demographic profile on
      elderly Africans. Also, it addresses challenges brought about by population aging
      and how it affects the provision of services to address the care giving needs of
      the elderly. Additionally, it examines the major features and limitations of
      current social insurance and retirement programs in Africa. Finally, it proposes
      measures to better meet the challenges brought about by population aging.

PMID- 12054269
TI  - Bifidobacterium scardovii sp. nov., from human sources.
AB  - Five strains of an unusual catalase-negative Gram-positive asporogenous rod
      shaped bacterium from human sources were subjected to a polyphasic taxonomic
      study. The presence of fructose-6-phosphate phosphoketolase, a key enzyme of
      bifidobacterial hexose metabolism, indicated the strains were members of the
      genus Bifidobacterium but they did not correspond to any of the recognized
      species of this genus on the basis of biochemical profiles and whole-cell protein
      analyses. Comparative 16S rRNA gene sequencing confirmed the placement of the
      isolates in the genus Bifidobacterium, and demonstrated they represent a hitherto
      unknown subline within the genus displaying > 5% sequence divergence with
      recognized species. Based on both phenotypic and phylogenetic criteria, it is
      proposed that the isolates recovered from human sources be classified as a new
      species, Bifidobacterium scardovii sp. nov.; the type strain is CCUG 13008T (=
      DSM 13734T).

PMID- 12054271
TI  - Applying work-role attachment theory to retirement decision-making.
AB  - This study examined the relationships between work-role attachment variables (job
      involvement, affective organizational commitment, and career identification) and
      intention to retire. Results indicated that organizational commitment was
      negatively related to retirement intent. Contrary to expectations, job
      involvement displayed a positive relationship and career identification had no
      relationship to retirement intent.

PMID- 12054272
TI  - A phenomenological study of wisdom in later life.
AB  - There is growing agreement that wisdom is multidimensional. But are the
      dimensions imputed to wisdom by recent theories congruent with major attributes
      of wisdom as lived by aging adults? Significant data exist on the attributes that
      various populations, including elderly populations, associate with wisdom. But
      there is little data available on what attributes and dimensions of wisdom emerge
      in descriptions of wisdom as lived by older adults. To produce such data, we
      adopted a phenomenological approach to wisdom. Interviews were conducted
      individually with six older adults. The interviews were audiotaped, transcribed,
      and analyzed using a qualitative software program known as MAX. We concluded that
      essential elements of wisdom as it is lived are Guidance, Knowledge, Experience,
      Moral Principles, Time, and Compassionate Relationships.

PMID- 12054273
TI  - Chronic illness and depressive symptoms among Chinese older adults: a
      longitudinal study.
AB  - Depression is quite common among the elderly members of Hong Kong Chinese
      society. This study examined the impact of a series of chronic illnesses on
      change in depressive symptoms among the older people. The respondents were 260
      people aged 70 years or older from a longitudinal study of a representative
      community sample of the elderly population in Hong Kong. Using multiple
      regression models, the authors found that, of six chronic illnesses examined,
      only arthritis was associated with depressive symptoms three years later, even
      after controlling socio-demographic, functional impairment, and social support
      variables were applied. Service and policy implications of the findings are
      discussed.

PMID- 12054274
TI  - Regret and psychological well-being among voluntarily and involuntarily childless
      women and mothers.
AB  - This study examines regret and psychological well-being among 72 middle-aged and
      older women who are either voluntarily childless, involuntarily childless, or
      mothers. Group comparisons indicate that, when compared to involuntarily
      childless women, voluntarily childless women show higher levels of overall well
      being, rate themselves as more autonomous with greater environmental mastery, and
      are less likely to have a child-related regret. An unexpected finding is that
      about one-third of women categorized by researchers as involuntarily childless
      indicate that they are "childless by choice." These women report making an active
      decision to accept the childless lifestyle and focus on the future, in essence
      exerting control over their situations. Results from this small and selective
      sample should be interpreted cautiously. However, they do suggest that
      researchers' definitions of childlessness may not map directly onto those of
      participants, and they emphasize the importance of ascertaining respondents'
      perceptions of control over their situations.

PMID- 12054275
TI  - First vaccine for cat AIDS approved for veterinary use.

PMID- 12054276
TI  - Australia lauded for emergency response.

PMID- 12054277
TI  - The provision of services to non-payers.

PMID- 12054278
TI  - Cases involving young dogs with limb fractures sustained in car accidents.

PMID- 12054279
TI  - What are the regulations regarding disposal of bodies and biological waste?

PMID- 12054280
TI  - Health problems of wild animals and the work of a wildlife veterinarian.

PMID- 12054281
TI  - Acute febrile neutrophilic vasculitis of the skin of young Shar-Pei dogs.
AB  - Three young Shar-Pei dogs were presented for signs of an acute widespread
      dermatopathy associated with fever and malaise. Cutaneous lesions initially
      consisted of multifocal areas of skin discolouration (haemorrhagic papules,
      macules or plaques) or oedema, preferentially affecting the head and limbs. In
      some locations, pus-filled bullae were evident also. Cutaneous lesions exuded
      seropurulent liquid and, in time, usually progressed to full thickness necrosis
      and ulceration. Lesions were so widespread and severe that one of the dogs was
      euthanased because its owners could not afford the reconstructive surgery
      required to close the skin deficits left at the completion of otherwise
      successful therapy. Histological examination of representative biopsies showed
      neutrophilic dermatitis and vasculitis, which ultimately resulted in ischaemic
      necrosis of skin. Therapy with immunosuppressive doses of corticosteroids, and in
      one case cyclophosphamide, resulted in prompt amelioration of the underlying
      inflammatory process, although regions of skin deprived of their blood supply
      eventually became necrotic and sloughed. Healing occurred through granulation,
      contraction and epithelialisation. The physical findings in these three dogs were
      so similar that it is likely all suffered from the same breed-related syndrome,
      an immune-mediated vasculitis precipitated by some event, such as vaccination or
      an undetected infection. Whatever the inciting cause, it was most likely a one
      off event, as the two surviving dogs were readily weaned off immunosuppressive
      medication without relapse.

PMID- 12054282
TI  - Cyclosporin and ketoconazole interaction for treatment of perianal fistulas in
      the dog.
AB  - OBJECTIVE: To assess the use of concurrent ketoconazole and low dose cyclosporin
      administration in a group of dogs with clinical evidence of perianal fistulas,
      and to determine if this combination could be used to manage perianal fistulas
      effectively. DESIGN: Prospective clinical trial PROCEDURE: Sixteen dogs with
      clinical evidence of perianal fistulas were given ketoconazole (10 mg/kg once
      daily) and cyclosporin (1 mg/kg twice daily initially) for 16 weeks. Blood
      cyclosporin assays were performed regularly and cyclosporin doses were altered to
      achieve a stable blood level above 200 ng/mL. Regular examinations assessed the
      dogs' general health, changes in clinical behaviour, fistula size and number. A
      complete blood count and serum biochemical analysis was performed in all dogs
      before and after the treatment period, and after 8 weeks of treatment in 12 dogs.
      Dogs were assessed for recurrence of lesions at 1, 3 and 12 months after the
      trial. RESULTS: All dogs showed marked improvement in lesions and behaviour
      within 14 days of the medication. Fourteen dogs completed the trial. Two dogs
      were excluded due to concurrent disease. Thirteen dogs (93%) showed complete
      resolution of fistulas during the treatment period. Seven dogs (50%) had no
      recurrence after 12 months. Recurrence was seen in three dogs (21%) at 8, 10 and
      12 months after treatment, and in three dogs (21%) within 1 month of treatment.
      The medication was well tolerated. Side effects included transient anorexia,
      vomiting and lethargy in some dogs, increased shedding of hair and gingival
      hyperplasia. Ketoconazole administration allowed a dramatic reduction in
      cyclosporin dose (over 90% in 12 dogs and 80% in the other two) compared to
      previously reported cases treated with cyclosporin alone. CONCLUSION: The use of
      combined ketoconazole and cyclosporin provided an effective treatment for
      perianal fistulas. Outcomes were similar to those seen with cyclosporin alone,
      but allowed a significant reduction in cyclosporin dose and, therefore, cost. The
      use of immunosuppressive therapy in the treatment of perianal fistulas was
      effective and avoided many of the problems associated with surgical treament.

PMID- 12054283
TI  - Acrylic cranioplasty and axial pattern flap following calvarial and cerebral mass
      excision in a dog.
AB  - A 4 kg Chihuahua was presented with seizures and a large mass on his dorsal
      cranium. The mass had regrown after two previous attempts to remove it.
      Histological examination had shown the mass to be a multilobular osteochondroma
      (osteochondrosarcoma). A CT scan revealed destruction of the dorsal cranial bones
      by the mass and compression of cerebral cortex. A craniotomy was performed to
      excise the mass and attached skin, leaving a large deficit of calvarial bone and
      skin. A cranioplasty was performed in situ, using polypropylene mesh and
      polymethyl methacrylate. A caudal auricular axial pattern flap was placed
      directly over the cranioplasty to fill the skin defect. This unusual
      reconstruction resulted in good recovery, function and cosmetic effect, although
      tumour regrowth was seen within the cerebral cortex.

PMID- 12054284
TI  - Emerging arboviral diseases.

PMID- 12054285
TI  - The effect of timing of administration of oestradiol benzoate on characteristics
      of oestrus, timing of ovulation and fertility in Bos indicus heifers synchronised
      with a progesterone releasing intravaginal insert.
AB  - OBJECTIVE: To compare the timing of onset of oestrus and ovulation,
      characteristics of oestrus, and fertility in Bos indicus heifers synchronised
      with a progesterone releasing intravaginal insert (IVP4) and administration of
      oestradiol benzoate (ODB) either at the time of removal of the insert or 24 h
      later. DESIGN: Cohort study. PROCEDURE: Bos indicus and Bos indicus cross heifers
      were treated on two farms (Farm A, n = 273; Farm B, n = 47) with an IVP4 for 8
      days with 1.0 mg of ODB administered at the time of device insertion and 250 mg
      of cloprostenol at the time of device removal. Heifers in the ODB-0 group were
      administered 0.75 mg of ODB at the time of device removal while heifers in the
      ODB-24 group were administered the same dose of ODB 24 h after device removal.
      Heifers were inseminated once daily after detection of oestrus. Heifers not
      detected in oestrus by 72 h after removal of inserts were inseminated at that
      time. Oestrus was detected in heifers on Farm A using heatmount detectors while
      on Farm B oestrus in heifers was monitored using radiotelemetry of mounting
      pressure. Ovarian follicular development was monitored daily in 30 heifers on
      Farm B from the time of administration of inserts until ovulation to a maximum of
      96 h after removal of inserts, and again 11 days after removal of inserts (Day
      19). A blood sample was collected from all heifers on Farm B on Day 19 and
      analysed for plasma concentration of progesterone. Pregnancy was diagnosed 6 to 8
      weeks after insemination. RESULTS: Administration of ODB at the time of removal
      of inserts shortened the time interval to oestrus and ovulation (P < 0.001),
      increased the number of mounts recorded during oestrus (P = 0.04) and reduced the
      odds of pregnancy (P = 0.03). The proportion of heifers ovulating on Farm B was
      67% and was not affected by treatment group (P = 0.61). The mean diameter of the
      largest follicle measured in ovaries was greater at the time of removal of
      inserts (9.1 +/- 0.6 vs 10.7 +/- 0.4; P = 0.03) and at the expected time of the
      LH surge (8.1 +/- 0.4 vs 11.5 +/- 0.3 mm; P < 0.001) in heifers that ovulated
      compared to heifers that failed to ovulate, respectively. Emergence of a new
      follicular wave was not detected during the synchronisation treatment in heifers
      that failed to ovulate. Concentrations of progesterone in plasma on Day 19 were
      less in non-pregnant heifers (P = 0.05) compared to heifers subsequently
      diagnosed as pregnant to insemination and were affected by the diameter of the
      ovulatory follicle (P = 0.01). CONCLUSION: Administration of ODB at the time of
      removal of inserts can shorten the time interval to oestrus and ovulation and can
      reduce fertility when insemination is carried out once daily. Further work is
      needed to determine if prolonged suppression of follicular development,
      anovulatory oestrus and premature ovulation occuring in some heifers is
      associated with administration of ODB.

PMID- 12054286
TI  - Effectiveness of copper oxide wire particles for Haemonchus contortus control in
      sheep.
AB  - OBJECTIVE: To assess the efficacy of copper oxide wire particles (COWP) for the
      control of H contortus infections in grazing sheep. PROCEDURE: In experiment 1,
      40 worm-free Merino hoggets (11 to 12 months of age) were divided into four equal
      groups and allocated to separate 0.8 ha pasture plots. Two groups then received
      2.5 g COWP whereas the other two groups were untreated. From 1 week after COWP
      treatment all lambs received a weekly infection of 2000 H contortus larvae. At
      week 8, six sheep from the untreated group were then allocated to two groups and
      treated with either 2.5 or 5.0 g of COWP to establish therapeutic efficacy of
      treatment. Experiment 2 followed a similar protocol but was conducted with 40
      worm-free Merino lambs (3 to 4 months of age) and no assessment of therapeutic
      efficacy was made. RESULTS: In experiment 1 no significant difference in faecal
      worm egg counts was observed between treatments and faecal worm egg counts
      remained less than 3000 epg in all animals. Total worm counts were reduced by 37%
      by COWP treatment (P = 0.055). Both 2.5 g and 5.0 g doses of COWP at 8 weeks of
      infection reduced faecal worm egg counts by > 85% with the higher dose giving an
      earlier response to treatment. In experiment 2, faecal worm egg counts at 4 and 6
      weeks were reduced by more than 90% in the COWP treated lambs and worm numbers
      were 54% lower after 6 weeks when all remaining untreated lambs had to be treated
      for haemonchosis. Mean faecal worm egg counts in the COWP lambs remained below
      3500 epg and clinical disease did not develop in the majority of lambs before the
      end of the experiment at 10 weeks. CONCLUSION: Treatment with COWPs appears to
      have the potential to reduce establishment and worm fecundity of Haemonchus spp
      for an extended period and may offer livestock producers a supplementary means of
      reducing larval contamination of pasture particularly in areas where anthelmintic
      resistance is a problem and copper supplementation is likely to be beneficial.

PMID- 12054288
TI  - Cytological and microbiological findings in guttural pouch lavages of clinically
      normal horses with head restraint.
AB  - OBJECTIVE: To evaluate the cytological and microbiological contents of guttural
      pouch washes of ten randomly selected horses restrained so as to prevent them
      lowering their heads, and to assess the possible effects on the guttural pouch
      environment in these horses. PROCEDURE: Cytological and microbiological studies
      were performed on guttural pouch washes of ten clinically normal horses
      restrained in a standing position so as to prevent them from lowering their heads
      below normal, as would happen during transportation on long journeys. They were
      restrained for 12 or 24 h and cytological, bacteriological and mycological
      findings in guttural pouch washes were recorded. RESULTS: The cytological
      gradings and neutrophil concentrations of guttural pouch washings were higher in
      horses that had their heads restrained for a longer period. Washings from these
      horses were more likely to contain cultivable bacteria and were the only washes
      yielding potentially pathogenic bacterial species. CONCLUSION: Variation in the
      cytological differential counts and bacterial cultures of guttural pouch lavages
      may be found in clinically normal horses which have had their heads restrained in
      an elevated position for periods from 12 to 24 h. This should be considered when
      examining this site and care must be taken when interpreting cytology of guttural
      pouch lavages in samples taken after transportation for more than 12 h.
      Restriction of head movement could also affect the normal pouch enviroment and
      predispose it to disease.

PMID- 12054287
TI  - A comparison of catecholamine and cortisol responses of young lambs and calves to
      painful husbandry procedures.
AB  - AIM: To compare the changes in plasma concentrations of noradrenaline, adrenaline
      and cortisol in lambs after ring castration plus tailing and in calves after
      dehorning with or without prior local anaesthesia. METHODS: Male lambs were
      castrated and tailed with rings and calves were dehorned by amputation using a
      scoop with or without prior local anaesthesia. Blood samples were taken before
      and after treatment and plasma concentrations of noradrenaline, adrenaline and
      cortisol were determined. RESULTS: Castration plus tailing of lambs resulted in a
      rapid increase in noradrenaline concentrations, a lack of an adrenaline response
      and a marked increase in cortisol concentration. There were similar changes in
      catecholamine concentrations in calves that were dehorned both with and without
      local anaesthetic, with adrenaline being elevated within 5 min of treatment and
      noradrenaline exhibiting a more protracted response. Dehorning caused a marked
      cortisol increase which was reduced to control concentrations by local
      anaesthesia for as long as the associated nerve blockade lasted. CONCLUSIONS: The
      very short-lived adrenaline responses in calves were attributed to dehorning
      induced nociceptor input leading to sympathetic stimulation of the adrenal
      medulla. The longer lasting noradrenaline responses in lambs and calves were
      thought be due to 'wash-out' of noradrenaline from damaged tissue associated with
      rings and amputation wounds, respectively.

PMID- 12054289
TI  - Questions of complexity.

PMID- 12054291
TI  - Determining the role that ecological and developmental constraints play in
      controlling disparity: examples from the crinoid and blastozoan fossil record.
AB  - It is widely believed that morphological constraints are responsible for the
      observed pattern of decreasing major morphological innovation in both the Metazoa
      and Metaphytes over geological time. This is readily seen as the decreasing trend
      of origination of higher taxa: phyla, classes, and orders. Currently, there are
      two competing evolutionary hypotheses that have been proposed to explain this
      phenomenon: (1) the empty ecospace hypothesis and (2) the developmental
      constraint hypothesis. To distinguish between hypotheses 1 and 2, the change of
      morphological innovation before and after several mass extinction events was
      measured in the Crinoidea and Blastozoa. Mass extinction intervals provided a
      means in which to remove ecospace limiting constraints and allow the
      developmental constraint hypothesis to be thoroughly tested. Within the
      Crinoidea, disparity was measured before and after three mass extinctions. Within
      the Blastozoa, disparity was measured before and after two mass extinctions. For
      each taxon, three suites of characters were analyzed: ecological, nonecological,
      or "developmental" and a combination of the two previous suites plus 50
      additional characters. Four different measures of disparity were used to analyze
      each character suite. In the majority of the cases investigated, disparity
      rebounds to comparable levels or in some cases higher levels in both the
      Crinoidea and Blastozoa. The results indicate that developmental constraints are
      not responsible for the decrease in disparity throughout the geologic range of
      the taxa. The more likely scenario is that increasingly structured ecological
      guilds have made it much more difficult to allow large increases in disparity.

PMID- 12054290
TI  - Why such long faces? Response to Collard and O'Higgins.

PMID- 12054293
TI  - Brachyury expression in tailless Molgulid ascidian embryos.
AB  - The T-box transcription factor gene Brachyury is important for the
      differentiation of notochord in all chordates, including the ascidians
      Halocynthia roretzi and Ciona intestinalis. We isolated Brachyury from molgulid
      ascidians, which have evolved tailless larvae multiple times independently, and
      found the genes appear functional by cDNA sequence analyses. We then compared the
      expression of Mocu-Bra in tailed Molgula oculata embryos to two tailless species,
      Molgula occulta (Mocc-Bra) and Molgula tectiformis (Mt-Bra). Here we show that
      both tailless species express Brachyury in the notochord lineage during
      embryogenesis. Initial expression of Mocu-Bra is normal in tailed M. oculata
      embryos; 10 precursor notochord cells divide twice to result in 40 notochord
      cells that converge and extend to make a notochord down the center of the tail.
      In contrast, in tailless Molgula occulta, Mocc-Bra expression disappears
      prematurely, and there is only one round of division, resulting in 20 cells in
      the final notochord lineage that never converge or extend. In M. occulta x M.
      oculata hybrid embryos, expression of Mocu-Bra is prolonged, and the embryos form
      a tail with 20 notochord cells that converge and extend normally. However, in
      Molgula tectiformis, a different tailless ascidian, Mt-Bra was expressed only in
      the 10 notochord precursor cells, which never divide, converge, or extend. In
      summary, neither Brachyury function nor the early establishment of the notochord
      lineage appears to be impaired in tailless embryos. In light of these results, we
      are continuing to investigate how and why notochord development is lost in
      tailless molgulid ascidian embryos.

PMID- 12054292
TI  - Patterns of gene expression in the developing adult sea urchin central nervous
      system reveal multiple domains and deep-seated neural pentamery.
AB  - The adult sea urchin central nervous system (CNS) is composed of five radial
      nerve cords connected to a circular nerve ring. Although much is known about the
      molecular mechanisms underlying the development and function of the nervous
      systems of many invertebrate and vertebrate species, virtually nothing is known
      about these processes in echinoderms. We have isolated a set of clones from a
      size-selected cDNA library prepared from the nervous system of the sea urchin
      Heliocidaris erythrogramma for use as probes. A total of 117 expressed sequence
      clones were used to search the GenBank database. Identified messages include
      genes that encode signaling proteins, cytoskeletal elements, cell surface
      proteins and receptors, cell proliferation and differentiation factors, transport
      and channel proteins, and a RNA DEAD box helicase. Expression was analyzed by RNA
      gel blot hybridization to document expression through development. Many of the
      genes have apparently neural limited expression and function, but some have been
      co-opted into new roles, notably associated with exocytotic events at
      fertilization. Localization of gene expression by whole-mount in situ
      hybridization shows that the morphologically simple sea urchin radial CNS
      exhibits complex organization into localized transcriptional domains. The
      transcription patterns reflect the morphological pentamery of the echinoderm CNS
      and provide no indication of an underlying functional bilateral symmetry in the
      CNS.

PMID- 12054294
TI  - Ontogenetic torsion in two basal gastropods occurs without shell attachments for
      larval retractor muscles.
AB  - Results of this study on two species of vetigastropods contradict the long
      standing hypothesis, originally proposed by Garstang (1929), that the larval
      retractor muscles power the morphogenetic movement of ontogenetic torsion in all
      basal gastropods. In the trochid Calliostoma ligatum and the keyhole limpet
      Diodora aspera, the main and accessory larval retractor muscles failed to
      establish attachments onto the protoconch (larval shell) when the antibiotics
      streptomycin sulfate and penicillin G were added to cultures soon after
      fertilization. Defects in protoconch mineralization were also observed. Despite
      these abnormalities, developing larvae of these species accomplished complete or
      almost complete ontogenetic torsion, a process in which the head and foot rotate
      by 180 degrees relative to the protoconch and visceral mass. Analysis by using
      phalloidin-fluorophore conjugate and transmission electron microscopy showed that
      myofilaments differentiated within myocytes of the larval retractor muscles and
      adherens-like junctions formed between muscle and mantle epithelial cells in both
      normal and abnormal larvae. However, in abnormal larvae, apical microvilli of
      mantle cells that were connected to the base of the larval retractor muscles
      failed to associate with an extracellular matrix that normally anchors the
      microvilli to the mineralized protoconch. If morphogenesis among extant, basal
      gastropods preserves the original developmental alteration that created gastropod
      torsion, as proposed by Garstang (1929), then the alteration involved something
      other than the larval retractor muscles. Alternatively, the developmental process
      of torsion has evolved subsequent to its origin in at least some basal gastropod
      clades so that the original alteration is no longer preserved in these clades.

PMID- 12054295
TI  - Evolutionary implications of developmental instability in parthenogenetic
      drosophila mercatorum. I. Comparison of several strains with different genotypes.
AB  - Natural populations of sexually reproducing Drosophila mercatorum are capable of
      a very low rate of parthenogenesis, but this mode of reproduction has apparently
      never characterized an entirely asexual population in this species. The high
      abortion rate observed in laboratory parthenogenetic lines suggests that
      developmental constraints may cause the failure of this trait to spread in
      nature. To investigate the basis of this developmental instability and how it may
      affect the evolution of parthenogenesis in natural populations, early embryonic
      development was compared between one sexual and four parthenogenetic laboratory
      strains of D. mercatorum. There is a large amount of variation within a given
      parthenogenetic strain, suggesting that parthenogenesis is associated with a
      general breakdown of developmental stability. There is relatively little
      variation among different parthenogenetic strains, suggesting that most abortions
      are due to a feature inherent to parthenogenetic reproduction rather than a
      feature of a particular genome. Likewise, there is little variation between
      parthenogenetic and sexual strains in the causes of abortions, suggesting that
      the developmental problems encountered by parthenogenetic lineages are not unique
      to parthenogens. Thus, the failure of parthenogenesis to spread within D.
      mercatorum can be attributed to no particular developmental constraint per se
      operating after the initiation of embryogenesis. However, the overall increase in
      all developmental problems that occurs with the transition from sexual to
      parthenogenetic development suggests that the high degree of developmental
      instability associated with parthenogenesis may be considered a developmental
      constraint in its own right.

PMID- 12054296
TI  - Evolutionary implications of developmental instability in parthenogenetic
      Drosophila mercatorum. II. Comparison of two strains with identical genotypes,
      but different modes of reproduction.
AB  - Developmental instability is particularly pronounced in parthenogenetic strains
      of Drosophila mercatorum. All parthenogenetically produced eggs in a given strain
      have the same genotype, but even when reared in the same environment, only
      approximately 5% of the eggs initiating development ever reach adulthood. A
      sexual analogue of a parthenogenetic strain was created to investigate the basis
      of this developmental instability. The two strains have identical genotypes
      (except for the Y chromosome in males of the sexual strain) and differ only in
      mode of reproduction. The sexual strain had a much lower rate of developmental
      instability than the parthenogenetic strain, suggesting that the instability is
      caused by the mode of reproduction per se and is not due to homozygosity,
      disruption of coadapted gene complexes, or any other feature of the
      parthenogenetic genome. The increased rate of abortion with parthenogenetic
      reproduction is caused by a proportional increase in the normal panoply of errors
      that occur in sexual reproduction but at a much lower rate. Attempts to establish
      other sexual analogues of laboratory parthenogenetic strains revealed different
      male sterility factors within several parthenogenetic genomes that could
      potentially act to prevent hybridization with sexually reproducing ancestors
      during the incipient stages in the evolution of an entirely parthenogenetic
      lineage.

PMID- 12054297
TI  - A diagnostic approach for the evaluation of spina bifida by three-dimensional
      ultrasonography.
AB  - OBJECTIVE: To describe a prenatal diagnostic method for evaluating spina bifida
      by three-dimensional ultrasonography. METHODS: Two- and three-dimensional
      ultrasonography were used to determine the extent of vertebral defects among
      fetuses with spina bifida. Spinal levels were independently counted from the most
      caudal thoracic vertebra with a rib (e.g., 12th thoracic rib). A virtual cutting
      plane was manipulated through a volume-rendered spine to generate optimal
      multiplanar views for this blinded analysis. Prenatal diagnosis was compared with
      a postnatal analysis of bony spine defects derived from radiographic films or
      magnetic resonance imaging. RESULTS: Nine fetuses were examined by two
      dimensional ultrasonography (21.8 +/- 3.4 menstrual weeks) and three-dimensional
      ultrasonography (22.8 +/- 4.4 menstrual weeks). For two-dimensional
      ultrasonography, the spinal level agreed to within 1 vertebral segment in 6 of 9
      infants. In contrast, three-dimensional ultrasonography agreed to within 1
      vertebral segment in 8 of 9 infants. Three fetuses had vertebral defect levels on
      two-dimensional ultrasonography that were 1.5 to 2 segments away from postnatal
      findings. The same fetuses had results that were within 1 vertebral segment on
      three-dimensional ultrasonography. Volume rendering showed splayed vertebral
      pedicles and disrupted vertebrae. An intact meningeal sac was easily rendered in
      5 of 9 subjects. CONCLUSIONS: Multiplanar views are generally more informative
      than rendered views for localizing bony defects of the fetal spine. The level of
      the defect on three-dimensional ultrasonography correlates well with those on two
      dimensional ultrasonography and postnatal imaging studies. This approach may
      improve characterization of spina bifida by adding diagnostic information that is
      complementary to the initial assessment by two-dimensional ultrasonography.

PMID- 12054298
TI  - Sonographic prenatal diagnosis of marginal placental cord insertion: clinical
      importance.
AB  - OBJECTIVE: To assess the impact of a sonographic diagnosis of marginal placental
      cord insertion on birth weight and duration of pregnancy. METHODS: A
      retrospective chart review was performed for 100 singleton pregnancies with
      prospectively identified marginal placental cord insertion. RESULTS: Birth
      weights below the 10th percentile occurred in 6.25% of pregnancies without
      preeclampsia. Spontaneous preterm delivery occurred in 7.3% of pregnancies
      without preeclampsia. Rates of birth weight below the 10th percentile and preterm
      delivery were not significantly different from those in the general population.
      Preeclampsia developed in 4 patients; all had elective preterm deliveries, and
      all gave birth to neonates with birth weights below the 10th percentile.
      CONCLUSIONS: A prenatal diagnosis of marginal placental cord insertion is not
      associated with increased risk of growth impairment or preterm delivery.

PMID- 12054299
TI  - Uterine artery embolization: sonographic imaging findings.
AB  - OBJECTIVE: To examine the sonographic and angiographic imaging findings before
      and after uterine fibroid embolization for symptomatic leiomyoma. METHODS: This
      prospective study involved 14 premenopausal women who underwent uterine fibroid
      embolization for symptomatic leiomyoma. Preprocedure sonography with color
      Doppler imaging was performed. Bilateral uterine artery embolization was
      successfully performed with the use of polyvinyl alcohol. Follow-up sonographic
      examinations were performed between 1 and 3 months after the procedure. The
      correlation between the sonographic appearance before and after embolization and
      the degree of decrease in uterine size was evaluated by using the Jonckheere
      Terpstra 2-sided P test. RESULTS: Preprocedure sonographic imaging showed a
      varied appearance to the fibroids. Color Doppler imaging primarily showed the
      fibroids to be vascular with marked peripheral blood flow. Postprocedure
      sonographic imaging showed decreased uterine size and echogenicity. Color Doppler
      imaging showed a marked decrease in the blood flow to the leiomyoma. There was no
      statistical significance in the relationship between echogenicity and vascularity
      shown before the procedure and the percent decrease in the size of the uterus.
      CONCLUSIONS: Although sonography is an efficient method for identifying
      leiomyomata and determining the reduction in size after uterine artery
      embolization, we were unable to identify any predictive characteristics of
      success for aiding the preprocedural assessment.

PMID- 12054300
TI  - Placental surface cysts detected on sonography: histologic and clinical
      correlation.
AB  - OBJECTIVE: To evaluate the clinical outcome and histologic findings of
      pregnancies in which placental surface cysts were detected on prenatal
      sonography. METHODS: A computerized search of our obstetric sonographic database
      from 1988 through 2000 identified 34 cases. Results of pathologic examinations,
      when performed, were obtained. Sonographic features were correlated with
      histologic findings and clinical parameters. RESULTS: On review of available
      microscopic slides, in all cases in which the cyst was seen at pathologic
      examination, there was subchorionic fibrin with central cyst formation. All
      pregnancies resulted in live births, although intrauterine growth restriction
      occurred in 4 (12%) of 34. Three (11%) of 28 cases with placental pathologic
      findings had maternal floor infarction. Only 2 significant associations between
      sonographic features and postnatal findings were found. In all cases of
      intrauterine growth restriction, average cyst size was larger than 4.5 cm. Of 12
      cysts larger than 4.5 cm, 4 (33%) had intrauterine growth restriction. Of 22
      cysts smaller than 4.5 cm, there were no instances of intrauterine growth
      restriction (P = .01). Of 32 cases with 3 or fewer cysts, only 2 had intrauterine
      growth restriction, whereas in 2 cases with more than 3 cysts, both had
      intrauterine growth restriction (P = .01). CONCLUSIONS: Most placental surface
      cysts are associated with a normal pregnancy outcome. Most such cysts are related
      to cystic change in an area of subchorionic fibrin. Cysts larger than 4.5 cm or
      more than 3 in number are more frequently associated with intrauterine growth
      restriction.

PMID- 12054301
TI  - Low-frequency ultrasound induces nonenzymatic thrombolysis in vitro.
AB  - OBJECTIVE: To evaluate whether ultrasound, applied over a distance of several
      centimeters and in the absence of thrombolytic agents, may have a thrombolytic
      effect on blood clots. METHODS: Low-frequency (20 kHz) continuous wave ultrasound
      at different intensity levels (0.15-1.2 W/cm2) and exposure times (5, 10, and 20
      minutes) was assessed for its potential to induce thrombolysis of fresh human
      blood clots. The ultrasound effect was also studied in combination with
      recombinant tissue-type plasminogen activator-mediated thrombolysis. Experiments
      were carried out in a flow model in degassed sodium phosphate buffer at 37
      degrees C at a distance of 3 cm from the ultrasonic probe to the blood clots.
      Regardless of ultrasound exposure times, blood clots in all experimental groups
      and the control group were left in the flow system for 20 minutes. RESULTS: The
      use of ultrasound alone showed a significant thrombolytic effect compared with
      the control group, with a statistically significant effect at 0.15 W/cm2 and
      exposure of 10 minutes (P = .02). There was a clear correlation between the
      extent of weight loss and the chosen intensity level and exposure time. Complete
      disruption in 8 of 10 blood clots occurred at 1.2 W/cm2 within 10 min. Addition
      of ultrasound to recombinant tissue-type plasminogen activator-mediated
      thrombolysis significantly enhanced thrombolysis compared with application of
      recombinant tissue-type plasminogen activator or ultrasound alone (P = .0001),
      with the results pointing toward a purely additive, nonsynergistic effect of the
      2 treatment modalities. Lysis was more effective in fresh thrombi. CONCLUSIONS:
      The use of low-frequency ultrasound alone, without addition of a thrombolytic
      drug, has the potential to induce thrombolysis over a distance. Combination of
      ultrasound with recombinant tissue-type plasminogen activator is superior to
      either treatment alone. Ultrasound is a promising tool for developing an
      alternative or additional treatment modality for acute cerebral vessel occlusion.

PMID- 12054302
TI  - Extensive wall thickening in intestinal Burkitt lymphoma.
AB  - OBJECTIVE: To evaluate intestinal lesions in Burkitt lymphoma. METHODS:
      Ultrasonography was used in the initial evaluation of 6 Japanese patients with
      intestinal Burkitt lymphoma. RESULTS: Ultrasonography revealed marked wall
      thickening of the colon from the cecum through either the ascending or the
      transverse colon, which led to a target sign (4 cases) or a pseudokidney sign (2
      cases). The target sign histopathologically corresponded to invagination of an
      occult tumor of the cecum into the ascending colon. Wall thickening of the colon
      when associated with a target or pseudokidney sign corresponded to marked lymph
      edema or a diffuse infiltration of Burkitt lymphoma cells into the intramural
      layers, respectively CONCLUSIONS: Ultrasonography provides useful information in
      the initial evaluation of intestinal lesions with distinctive histopathologic
      characteristics in Burkitt lymphoma.

PMID- 12054303
TI  - Unusual "to-and-fro" Doppler spectral waveform in lymph node metastasis.

PMID- 12054304
TI  - Scrotal lymphangioma: an uncommon cause for a scrotal mass.

PMID- 12054305
TI  - Milk of calcium in a tunica albuginea cyst.

PMID- 12054306
TI  - Long-term sonographic follow-up of stable imaging findings of multiseptate
      gallbladder.

PMID- 12054307
TI  - Unusual sonographic appearance of a large fetal cardiac rhabdomyoma: antenatal
      diagnosis and treatment.

PMID- 12054308
TI  - Ovarian cystic teratoma: determined phenotypic response of keratocytes and
      uncommon intracystic floating balls appearance on sonography and computed
      tomography.

PMID- 12054309
TI  - Intramural duodenal hematoma mimicking an intestinal mass on sonography.

PMID- 12054310
TI  - Color Doppler examination of a regressing pulmonary artery pseudoaneurysm due to
      Behcet disease.

PMID- 12054311
TI  - Acute thrombosis of a giant portal venous aneurysm: value of color Doppler
      sonography.

PMID- 12054312
TI  - Sonographic diagnosis and treatment of a median nerve epineural hematoma caused
      by brachial artery catheterization.

PMID- 12054313
TI  - Three-dimensional fetal brain volumes.

PMID- 12054314
TI  - Self-appraised problem solving and pain-relevant social support as predictors of
      the experience of chronic pain.
AB  - The purpose of this study was to examine the contributions of self-appraised
      problem-solving competence and pain-relevant social support to the prediction of
      pain, depression, and disability. The 234 chronic pain patients referred for
      participation in a comprehensive pain management program were administered self
      report measures of pain, depression, disability, pain-relevant social support,
      and problem solving. Hierarchical multiple-regression analyses revealed that
      lower self-appraised problem-solving competence was related to increased pain,
      depression, and disability. Pain-relevant social support was directly related to
      pain and disability but indirectly related to depression. High levels of pain
      relevant social support were found to buffer the relation between poorer self
      appraised problem-solving competence and depressive symptoms. The results support
      the assessment of problem-solving skills in chronic pain patients and the
      investigation and utility of interventions aimed at increasing adaptive pain
      relevant social support.

PMID- 12054315
TI  - Perception of cognitive performance in patients with chronic fatigue syndrome.
AB  - This study examined discrepancies between perceived and actual performance by
      patients with chronic fatigue syndrome (CFS) confronted with a challenging
      cognitive task. Before and after completing a modified version of the Stroop
      task, 40 patients and 40 healthy control participants estimated their own
      performance and the performance that would normally be achieved by someone of
      equal age and education level. After correcting for differences between the
      groups in depression, we found no differences in actual performance on the
      Stroop. However, patients with CFS consistently underestimated their performance
      relative to normal performance. This difference was observed for both depressed
      and nondepressed subgroups of patients, persisted after adjusting the results for
      depression, and correlated with patients' ratings of the mental effort and
      fatigue evoked by the task. The results are discussed in light of cognitive
      models of CFS that suggest the setting of impossibly high standards of personal
      performance may contribute to the dynamism of this disease.

PMID- 12054316
TI  - Cardiovascular stress responses among Asian Indian and European American women
      and men.
AB  - Asian Indians have approximately 3 times the rate of coronary artery disease as
      do age-matched European Americans, but the increased risk cannot be explained by
      the presence of known physiological and behavioral risk factors. One previous
      study suggested that Asian Indians have diminished vasoactive responses to
      isoproterenol, but no published study has examined responses to psychological
      stressors. The purpose of this study was to test the hypothesis that the
      vasomotor response to stress, as indexed by hemodynamic measures, would be
      exaggerated in Asian Indian men and women, relative to European American
      individuals. Thirty-seven Asian Indian and 43 European American men and women
      were tested in a standard reactivity protocol, whereas heart rate, blood
      pressure, and cardiac impedance measures were assessed. Asian Indian men and
      women had significantly smaller changes in systolic blood pressure and mean
      arterial pressure during the stressors, relative to European American men and
      women. Asian Indian women, but not men, had significantly smaller diastolic blood
      pressure and total peripheral-resistance index changes to the stressors, relative
      to the other 3 groups. These data are in contrast to our expectation of decreased
      tendency of Asian Indians to vasodilate during psychological stress but do
      suggest that sex and Asian Indian ethnicity interact to influence vascular
      reactivity to stressors.

PMID- 12054317
TI  - Audience status moderates the effects of social support and self-efficacy on
      cardiovascular reactivity during public speaking.
AB  - Exaggerated blood pressure responses to stress are implicated in the development
      of cardiovascular disease, and an effort has been made to identify factors
      associated with such responses. One situational factor that impacts
      cardiovascular responses to stress is the presence of other people and their
      behavior. Here, we manipulated the status of the audience during a stressful
      public speaking task to explore its impact on reactivity and its possible role in
      moderating the effects of the speaker's confidence and the audience's response
      during the speech. Sixty-four normotensive female undergraduates, classified as
      having high or low self-efficacy for public speaking, gave a 5-min speech to an
      audience that responded positively or negatively. Half of the audiences were
      presented as public speaking experts and half as novices. Cardiovascular
      reactivity was greater for low-efficacy speakers and for those receiving positive
      feedback. Reactivity was also greater facing an expert audience. Furthermore, the
      effects of both self-efficacy and audience feedback were intensified before an
      expert audience. To understand social support effects, we must attend not only to
      characteristics of the recipient but also to those of the provider.

PMID- 12054318
TI  - Coping in normal pregnancy.
AB  - BACKGROUND: In high-risk populations (e.g., adolescents, substance abusers),
      coping strategies in pregnancy have been studied. Avoidance of the stressful
      situation and aggressive coping are frequently used and related to postnatal
      depression and other negative outcomes. Little is known about coping strategies
      in nulliparous normal-risk pregnancy. OBJECTIVE: To examine the factor structure
      of the 19-item Utrecht Coping List (UCL-19) in a sample of nulliparous normal
      risk pregnant women and to explore the stability, change, and correlates of
      coping strategies throughout pregnancy. The associations between a particular
      coping strategy and the reported pregnancy complaints and experienced distress
      were examined. METHODS: The UCL-19 was filled out and self-report data were
      collected about neuroticism, locus of control, depression, general anxiety,
      perceived stress, and physical pregnancy complaints in nulliparous women in
      early, mid-, and late pregnancy. RESULTS: Confirmatory factor analysis on the UCL
      19 revealed 2 coping strategies: emotion-focused coping and problem-focused
      coping. The factor structure of the UCL-19 had a good stability throughout
      pregnancy. Some changes in emotion-focused coping and problem-focused coping
      scores were found, although the absolute differences were rather small. High
      educational level and low internal locus of control predicted a high score on
      emotion-focused coping in the early period of pregnancy, F(2, 228) = 11.49, p <
      .005, R2 = .22. High educational level also predicted a high score on problem
      focused coping in early pregnancy, F(1, 229) = 4.80, p < .05, R2 = .06. Emotion
      focused coping was negatively and problem-focused coping was positively related
      to pregnancy complaints (r = -.23, p < .05 and r = .25, p < .005, respectively).
      Emotion-focused coping in early pregnancy and problem-focused coping in mid
      pregnancy were negatively related to experienced distress in early and mid
      pregnancy, respectively (r = -.27, p < .0005 and r = -.18, p < .01). CONCLUSION:
      Two coping strategies were consistently found throughout pregnancy: emotion
      focused coping and problem-focused coping. Coping in nulliparous normal-risk
      pregnancy is a process with small temporal variations. Emotion-focused coping was
      negatively related to the number of reported pregnancy complaints and to
      experienced distress.

PMID- 12054319
TI  - Thoughts of suicide among HIV-infected rural persons enrolled in a telephone
      delivered mental health intervention.
AB  - This study characterized rates and predictors of suicidal thoughts among HIV
      infected persons living in rural communities of eight U.S. states. Self
      administered surveys were completed by 201 HIV-infected persons living in
      communities of 50,000 or fewer that were located at least 20 miles from a city of
      100,000 or more. All participants were clients of rural AIDS service
      organizations and had recently enrolled into a randomized clinical trial of a
      telephone-delivered, coping improvement-group intervention designed specifically
      for HIV-infected rural persons. At baseline, participants reported on thoughts of
      suicide, psychological symptomatology, life-stressor burden, ways of coping,
      coping self-efficacy, social support, and barriers to health care and social
      services. Thirty-eight percent of HIV-infected rural persons had engaged in
      thoughts of suicide during the past week. A logistic regression analysis revealed
      that participants who endorsed thoughts of suicide also reported more depressive
      symptoms (odds ratio [OR] = 2.19; 95% confidence interval [CI] = 1.32-3.63, p <
      .002), less coping self-efficacy (OR = 0.70; 95% CI = 0.56-0.88, p < .002), more
      frequently worried about transmitting their HIV infection to others (OR = 1.66,
      95% CI = 1.14-2.40, p < .008), and experienced more stress associated with AIDS
      related stigma (OR = 1.58, 95% CI = 1.07-2.35, p < .03). As AIDS prevalence rates
      increase in rural areas, interventions that successfully identify and treat
      geographically isolated HIV-infected persons who experience more frequent or
      serious thoughts of suicide are urgently needed.

PMID- 12054320
TI  - Social cognitive determinants of physical activity in young adults: a prospective
      structural equation analysis.
AB  - This study used a prospective design to test a model of the relation between
      social cognitive variables and physical activity in a sample of 277 university
      students. Social support, self-efficacy, outcome expectations, and self
      regulation were measured at baseline and used to predict physical activity 8
      weeks later. Results of structural equation modeling indicated a good fit of the
      social cognitive model to the data. Within the model, self-efficacy had the
      greatest total effect on physical activity, mediated largely by self-regulation,
      which directly predicted physical activity. Social support indirectly predicted
      physical activity through its effect on self-efficacy. Outcome expectations had a
      small total effect on physical activity, which did not reach significance. The
      social cognitive model explained 55% of the variance observed in physical
      activity.

PMID- 12054321
TI  - Challenges to improving the impact of worksite cancer prevention programs:
      comparing reach, enrollment, and attrition using active versus passive
      recruitment strategies.
AB  - OBJECTIVE: The impact of worksite intervention studies is maximized when reach
      and enrollment are high and attrition is low. Differences in reach, enrollment,
      and retention were investigated by comparing 2 different employee recruitment
      methods for a home-based cancer-prevention intervention study. METHODS: Twenty
      two worksites (N = 10,014 employees) chose either active or passive methods to
      recruit employees into a home-based intervention study. Reach (e.g., number of
      employees who gave permission to be called at home), Enrollment (e.g., number of
      employees who joined the home intervention study), and Attrition (e.g., number
      who did not complete the 12- and 24-month follow-ups) were determined. Analysis
      at the cluster level assessed differences between worksites that selected active
      (n = 12) versus passive (n = 10) recruitment methods on key outcomes of interest.
      Employees recruited by passive methods had significantly higher reach (74.5% vs.
      24.4% for active) but significantly lower enrollment (41% vs. 78%) and retention
      (54% vs. 70%) rates (all ps < .0001). Passive methods also successfully enrolled
      a more diverse, high-risk employee sample. Passive (vs. active) recruitment
      methods hold advantages for increased reach and the ability to retain a more
      representative employee sample. Implications of these results for the design of
      future worksite studies that involve multilevel recruitment methods are
      discussed.

PMID- 12054322
TI  - A commentary on Sallis, Owen, and Fotheringham's perspective on "Behavioral
      epidemiology: a systematic framework to classify phases of research on health
      promotion and disease prevention".

PMID- 12054324
TI  - Counterbalancing patient demands with evidence: results from a pan-Canadian
      randomized clinical trial of brief supportive-expressive group psychotherapy for
      women with systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the effect of Brief Supportive-Expressive Group
      Psychotherapy as an adjunct to standard medical care in reducing psychological
      distress, medical symptoms, and health care costs and improving quality of life
      in women with systemic lupus erythematosus (SLE). METHODS: A randomized clinical
      trial was conducted with 133 SLE female patients from 9 clinics across Canada.
      Clinical and psychosocial measures were taken at baseline, posttreatment, and 6
      and 12 months posttreatment. Outcomes assessed were psychological distress,
      quality of life, disease activity, health service utilization, and diminished
      productivity. RESULTS: Intention-to-treat analyses revealed that there were no
      clinically important group differences on any of the outcome measures.
      CONCLUSION: Although both groups improved over time on several measures (e.g.,
      decreases in psychological distress, stress, and emotion-oriented coping), these
      changes could not be attributed to the psychotherapeutic intervention. Thus,
      evidence does not support the referral of these patients to this type of
      intervention.

PMID- 12054323
TI  - Self-management aspects of the improving chronic illness care breakthrough
      series: implementation with diabetes and heart failure teams.
AB  - Self-management is an essential but frequently neglected component of chronic
      illness management that is challenging to implement. Available effectiveness data
      regarding self-management interventions tend to be from stand-alone programs
      rather than from efforts to integrate self-management into routine medical care.
      This article describes efforts to integrate self-management support into broader
      health care systems change to improve the quality of patient care in the Chronic
      Illness Care Breakthrough Series. We describe the general approach to system
      change (the Chronic Care Model) and the more specific self-management training
      model used. The process used in training organizations in self-management is
      discussed, and data are presented on teams from 21 health care systems
      participating in a 13-month-long Breakthrough Series to address diabetes and
      heart failure care. Available system-level data suggest that teams from a variety
      of health care organizations made improvements in support provided for self
      management. Improvements were found for both diabetes and heart failure teams,
      suggesting that this improvement process may be broadly applicable. Lessons
      learned, keys to success, and directions for future research and practice are
      discussed.

PMID- 12054326
TI  - Chips with everything.

PMID- 12054325
TI  - Fat content of chips, quality of frying fat and deep-frying practices in New
      Zealand fast food outlets.
AB  - OBJECTIVES: To collect baseline data on the fat content of hot chips, quality
      (degradation) of cooking fat, deep-frying practices and related attitudes in fast
      food outlets in New Zealand. To identify the key determinants of the fat content
      of chips and quality of cooking fat. METHODS: A nationally representative sample
      of fast food outlets (n=150, response rate 80%) was surveyed between September
      1998 and March 1999. Data collected included a questionnaire, observation of
      cooking practices and analysis of cooked chips and frying fat. RESULTS: Only 8%
      of independent operators had formal training in deep frying practices compared
      with 93% of chain operators. There was a wide range of fat content of chips (5%
      20%, mean 11.5%). The use of thinner chips, crinkle cut chips and lower fryer fat
      temperature were associated with higher chip fat content. Eighty-nine per cent of
      chain outlets used 6-10 mm chips compared with 83% of independent outlets that
      used chips > or = 12 mm. A wide range of frying temperatures was recorded (136
      233 degrees C) with 58% of outlets frying outside the reference range (175-190
      degrees C). As indices of fat degradation, fat acid and polar compound values
      above the recommended levels occurred in 54% and 5% of outlets respectively.
      Operators seemed willing to learn more about best practice techniques, with lack
      of knowledge being the main barrier to change. CONCLUSIONS AND IMPLICATIONS: Deep
      frying practices could be improved through operator training and certification
      options. Even a small decrease in the mean fat content of chips would reduce the
      obesogenic impact of this popular food.

PMID- 12054327
TI  - An investigation of professional advice advocating therapeutic sun exposure.
AB  - OBJECTIVE: To determine the prevalence of inappropriate professional advice
      advocating therapeutic sun exposure in infancy and the post-partum period.
      METHODS: Self-administered postal questionnaires were completed by doctors
      (n=130; 71% response) and nurses (n=285; 58.6% response) responsible for the care
      of post-parturient women in eight hospitals in metropolitan and regional
      Queensland (1999/2000). RESULTS: Both groups reported several risky beliefs about
      the therapeutic benefits of sun exposure including using sunlight to treat:
      cracked nipples (41.1% nurses, 46.2% doctors); neonatal jaundice (49.5%, 34.9%);
      nappy rash (23.3%, 19.5%); and acne (12.3%, 20.2%). Approximately 10% of nurses
      and doctors recommended sunlight to treat sore/cracked nipples from
      breastfeeding, while 42% recommended sun exposure to treat neonatal jaundice.
      Relatively few doctors and nurses who recommended therapeutic sun exposure
      stipulated sunning through a window. Subtropical residence was a significant
      predictor of recommending sunlight to treat cracked nipples (p=0.002) and nappy
      rash (p=0.0005) among nursing staff. Midwives were more likely to recommend
      sunlight for neonatal jaundice than other nurses (p=0.004). Obstetricians
      (p=0.046), older doctors (p=0.049) and those who qualified earlier (p=0.031) were
      more likely to recommend sunlight to treat nappy rash. Paediatricians and
      neonatologists were less likely to recommend sunlight to treat neonatal jaundice
      than obstetricians and other doctors (p=0.009). CONCLUSIONS AND IMPLICATIONS: An
      education program is needed to change the practices of health professionals who
      recommend therapeutic sun exposure and should coincide with a health promotion
      campaign aimed at reducing the prevalence of related risky beliefs among parents.

PMID- 12054328
TI  - Predictors of falls in the Melbourne visual impairment project.
AB  - OBJECTIVE: To assess factors associated with falls in the past month, including
      visual acuity and other vision-related variables. METHODS: A household census was
      used to recruit permanent residents aged 40 years and older for baseline
      examinations of the Melbourne Visual Impairment Project conducted from 1992-94.
      At the five-year follow-up examinations, returning participants were asked to
      recall all falls that they had ever experienced and also how many falls they had
      experienced in the past month. Falls history was divided into those that occurred
      at home and away from home. Standardised examination of visual acuity was
      performed. RESULTS: Of the original cohort of 3,271, 231 (7.1%) were reported to
      have died, leaving 3,040 eligible. Of these, 2,594 (85%) were examined, 51 (2%)
      had moved interstate or overseas, 83 (3%) could not be traced, and 312 (10%)
      refused to participate. A history of having ever fallen at home was reported by
      466 (20%) participants, and 406 (17.3%) reported having fallen away from home at
      least once. Five per cent of the cohort (129/2,343) had fallen in the previous
      month. Factors significantly related to falls at home in the past month in a
      multivariate logistic regression model included age (OR=1.56 for 10-year age
      groups) and nuclear cataract (OR=2.87). CONCLUSIONS: Irrespective of visual
      acuity, cataract is major risk factor for falls at home. IMPLICATIONS:
      Interventions aimed at decreasing the incidence of falls in the community should
      include assessment of both visual acuity and cataract status and referral for
      treatment if functional impairment is evident.

PMID- 12054329
TI  - Historical and cultural roots of tobacco use among Aboriginal and Torres Strait
      Islander people.
AB  - Tobacco smoking has been identified as a major contributor to the high morbidity
      and mortality rates of Aborigines and Torres Strait Islanders. After years of
      inattention, smoking cessation projects designed for Indigenous Australians are
      beginning to emerge. Dealing successfully with smoking cessation would be
      enhanced by an understanding of the long-standing historical, social and cultural
      antecedents to present-day usage of tobacco. This paper provides a brief account
      of the historical precursors to present-day patterns of tobacco use among
      Aboriginal and Torres Strait Islander people. Historical records and mission
      documents, together with ethnographic accounts, suggest that Indigenous tobacco
      use today demonstrates strong continuity with past patterns and styles of use.
      These sources also reveal that Europeans deliberately exploited Aboriginal
      addiction to nicotine.

PMID- 12054330
TI  - Teenage pregnancy: trends, characteristics and outcomes in South Australia and
      Australia.
AB  - OBJECTIVES: To describe trends in teenage pregnancy rates in South Australia and
      Australia in 1970-2000, and the socio-demographic and clinical characteristics
      and outcomes of teenage women who gave birth in South Australia in 1995-99.
      METHODS: A descriptive study using population-based legislated South Australian
      perinatal and abortion data, Australian Medicare and hospital morbidity data on
      abortions, and birth registration rates from the Australian Bureau of Statistics.
      RESULTS: The teenage pregnancy rate in South Australia fell in the 1970s and
      1980s, increased in the 1990s, but is declining at the turn of the century.
      Teenage abortions exceeded livebirths annually from 1994, and in 2000 the teenage
      abortion, birth and pregnancy rates were 22.4,18.3 and 40.8 per 1,000
      respectively. The Australian rates, which are an underestimate, follow the South
      Australian trends and are declining but still much higher than in many western
      European countries. High socio-economic areas in South Australia have the lowest
      teenage pregnancy rates but the highest proportion of teenage pregnancies
      terminated. Teenagers who gave birth were more likely than older women to be
      Australian-born, Aboriginal, smokers during pregnancy (47% vs. 23%), to attend
      few antenatal visits, and to have preterm, small-for-gestational-age and low
      birthweight babies and neonatal deaths. Perinatal mortality has halved among
      teenagers under 17 years in the past decade. CONCLUSIONS AND IMPLICATIONS: Births
      to South Australian teenage women are associated with social disadvantage and
      relatively poor perinatal outcomes, although these have improved. Current
      strategies are aimed at reducing the incidence of unplanned teenage pregnancy and
      improving support for pregnant teenagers.

PMID- 12054331
TI  - Prevalence and socio-economic correlates of smoking among lone mothers in
      Australia.
AB  - OBJECTIVE: To report smoking prevalence among Australian lone mothers by age and
      socio-economic group and to examine the extent to which the difference in smoking
      prevalence between lone mothers and other women is due to socio-economic factors.
      METHODS: This was a secondary analysis of data from the 1995 National Health
      Survey (NHS), which was conducted by the Australian Bureau of Statistics (ABS).
      Information was collected from 53,800 respondents using face-to-face interviews.
      This analysis was limited to single mothers (n=1,184) who had at least one
      dependent child aged under 15. The outcome measure was smoking status,
      distinguishing regular smokers from occasional smokers, ex-smokers and never
      smokers. RESULTS: The overall smoking prevalence among lone mothers was 46.3% (Cl
      43.5%-49.1%). Lone mothers who were younger, less educated, received government
      pension/benefits, occupied rental housing or who lived in more disadvantaged
      areas were more likely to smoke than others. A strong 'lone mother effect'
      remained after controlling for socio-economic variables. The odds of smoking for
      lone mothers were 2.4 times greater than for married mothers (95% Cl 2.0-2.9) and
      twice as large as those for women living alone (95% CI 1.62.4). CONCLUSION: As
      the prevalence for this population group is considerably higher than the
      prevalence for other women within each age category, programs to assist lone
      mothers to quit smoking are a priority for the long-term health of these women
      and their children. Furthermore, we discuss how policies and interventions that
      enhance the material conditions and social circumstances of lone mothers can
      bring about a decline in their smoking prevalence.

PMID- 12054332
TI  - Comparing health inequalities among men aged 18-65 years in Australia and England
      using the SF-36.
AB  - OBJECTIVE: To compare the distribution of the domains and summary scores of the
      SF-36 health survey by occupation-related social classes in England and Australia
      for employed males age 18-65 years. METHOD: Relative and absolute measures of
      inequality based on the concentration index were used to examine the distribution
      of indicators of reported health based on domains and summary scores of the SF-36
      across occupation-related social classes in both countries. RESULTS: The degree
      of inequality is most pronounced in the domains and summary scores of the SF-36
      representing aspects of physical health. In regard to comparisons between these
      countries, there is no significant difference in the distribution of summary
      scores for physical health. Although there are differences in the summary scores
      for mental health, there is no evidence of significant inequality in Australia in
      this aspect of health. CONCLUSIONS: There is a similar pattern of occupation
      related health inequality in the physical health dimensions of the SF-36 health
      survey for employed males age 18-65 years. IMPLICATIONS: Given the similarities
      in the distribution of measures of physical health in the two countries, it would
      be useful to assess recent English policy initiatives aimed at reducing health
      inequalities when developing interventions to tackle inequalities in Australia.

PMID- 12054333
TI  - Obesity, diabetes and associated cardiovascular risk factors among Torres Strait
      Islander people.
AB  - OBJECTIVE: To describe the lifestyle-related chronic disease and risk factor
      prevalence among Torres Strait Islander people of the Torres Strait and Northern
      Peninsula Area Health Service District and to compare this information with that
      available for the general Australian population. METHODS: Voluntary community
      based screening for persons aged 15 years and older, including oral glucose
      tolerance test, anthropometry, health questionnaire, measurement of lipids and
      lipoprotein levels, blood pressure and urinary albumin to creatinine ratio.
      RESULTS: Nine communities participated in screening between 1993 and 1997. Five
      hundred and ninety-two participants (286 male and 306 female) identified as
      Torres Strait Islander. There were high prevalences of overweight (30%), obesity
      (51%), abdominal obesity (70%), diabetes (26%), hypercholesterolaemia (33%),
      albuminuria (28%), hypertension (32%) and tobacco smoking (45%). Only 8.5% of men
      and 6.5% of women were free of any cardiovascular risk factors (abdominal
      obesity, hypercholesterolaemia, hypertension, dyslipidaemia, smoking, diabetes,
      albuminuria). Comparisons of this information for Torres Strait Islander people
      with results from the AusDiab survey show rates of obesity three times higher and
      diabetes six times higher than for other Australians. CONCLUSIONS: There is a
      very high prevalence of preventable chronic disease and associated risk factors
      among Torres Strait Islander people of the Torres Strait and Northern Peninsula
      Area. IMPLICATIONS: Effective interventions to prevent and manage obesity,
      diabetes and associated cardiovascular risk factors are essential if the health
      of the Torres Strait Islander people is to improve. Such interventions could
      inform initiatives to stem the burgeoning epidemic of obesity and diabetes among
      all Australians.

PMID- 12054334
TI  - Trends in neural tube defects in Western Australia.
AB  - OBJECTIVE: To report on trends in neural tube defects in Western Australia, in
      relation to folate promotion, periconceptional use of folic acid supplements and
      food fortification with folate. METHODS: Data on neural tube defects from the
      Western Australian Birth Defects Registry. RESULTS: A 30% fall in neural tube
      defects was documented from 1996 to 2000. CONCLUSIONS AND IMPLICATIONS: The
      sustained fall in neural tube defects is thought to be due to increased
      periconceptional folate intake in response to health promotion campaigns and
      fortification of selected foods. There is room for further improvement.

PMID- 12054335
TI  - Accurate sampling in general practice waiting room surveys: methodological
      issues.
AB  - OBJECTIVES: This is a pilot study to test the validity of using one research
      assistant to train and support reception staff at five clinics to obtain waiting
      room data in general practice surveys. DESIGN: A research assistant trained
      reception staff at five randomly chosen general practices to administer a survey
      to all eligible women over a two-week period. Practices were audited daily by
      their appointment books and where possible by billing records to check total
      numbers of eligible women to determine the denominator of the sample. SETTING:
      Five metropolitan general practices in one divisional area. PARTICIPANTS: Twenty
      five receptionists distributed surveys to 1,298 women. MAIN OUTCOME MEASURES:
      Number of eligible women missed at each clinic. RESULTS: The number of potential
      subjects missed by the reception staff ranged from nil to 18% with the
      appointment book audit. A second audit using billing records at three clinics
      revealed inaccuracies of up to 50%. The ability to accurately capture eligible
      patients for waiting room surveys depends on good administrative systems within
      the practice and motivated staff. CONCLUSIONS: It is important for general
      practice researchers to consider and account for eligible participants who are
      missed from the denominator with a waiting room survey method. Valid sampling
      using this method can be achieved in certain practices, however this may limit
      the generalisability of the findings.

PMID- 12054336
TI  - Changes in the use of tobacco among Australian secondary students: results of the
      1999 prevalence study and comparisons with earlier years.
AB  - OBJECTIVE: To estimate smoking prevalence among Australian secondary students in
      1999 and to examine trends in smoking-related behaviours since 1984. METHOD: A
      randomly selected representative sample of 399 secondary schools from across
      Australia participated in the study. At each school, up to 80 randomly selected
      students completed a pencil-and-paper questionnaire anonymously. Data from 25,486
      students aged between 12 and 17 years are reported. RESULTS: Current smoking
      (smoking in the week before the survey) was 6% in boys and girls aged 12, and
      rose to a peak prevalence among 17-year-olds of 33% for boys and 30% for girls.
      Comparisons across survey years showed that while fewer 12-to-15-year-olds were
      current smokers in 1999 than in 1996, among 16- and 17-year-olds, the proportion
      of current smokers in 1999 and 1996 was similar. Students who smoked were less
      likely to buy their cigarettes in 1999 than in previous surveys. Both older and
      younger secondary students were more likely to have received lessons about
      tobacco in the school year prior to the 1999 survey than were students in the
      1996 survey. CONCLUSION: The rise in the prevalence of smoking among younger
      secondary students seen in the 1990s seems to have stopped and smoking prevalence
      has declined. IMPLICATIONS: Extrapolating from this survey, we estimate that
      nearly 269,000 12-to-17-year-old students were current smokers in 1999. If they
      all continue to smoke, 134,000 would die prematurely.

PMID- 12054337
TI  - Increasing 'active prevalence' of cancer in Western Australia and its
      implications for health services.
AB  - OBJECTIVE: To measure the active and total prevalence of cancer in Western
      Australia from 1990-98 and to examine trends in utilisation of hospital services
      by prevalent cancer patients. METHOD: Longitudinal analysis of linked cancer
      registrations, hospital separations and death registrations in Western Australia
      in 1990-98 using a population-based record linkage system. RESULTS: There was an
      estimated total of 53,450 patients ever-diagnosed with cancer in Western
      Australia at 30 June 1998 (29.7 per 1,000 population), an increase of 51% since
      mid-1990 (21.9/1,000). Patients with active disease accounted for 25% of the
      total prevalence, and the active prevalence of cancer increased from 5.1/1,000 in
      1990 to 7.4/1,000 in 1998. In patients with active cancer, hospital admission
      rates for procedures other than chemotherapy and radiotherapy were stable or
      declining, but admission rates for chemotherapy and radiotherapy increased. The
      annual average cumulative length of stay decreased. CONCLUSIONS AND IMPLICATIONS:
      There has been a rapid increase in the number of prevalent patients requiring
      health care services for cancer during the 1990s. Most of the increase is due to
      improved survival, population growth and ageing. Further strain on Australian
      health care expenditure seems inevitable.

PMID- 12054338
TI  - Prevalence of South Australia's online health seekers.
AB  - OBJECTIVE: To determine the proportion of South Australians accessing online
      health care information, predictive characteristics of online health seekers,
      nature of the information sought and consumer behaviour. METHODS: A probability
      based survey of 3,027 South Australians, aged 15 years and older, as part of the
      Spring 2000 South Australian Health Omnibus. RESULTS: Internet access decreases
      with age, while the prevalence of online health seekers is constant (26% to 28%)
      among people aged between 15 and 54 years. Predictive characteristics of online
      health seekers include gender, age, education and income. Most commonly sought
      information is the cause or description of disease (60%). Consumers use online
      health information as a second opinion (19%), discuss it with their doctor or
      pharmacist (16%), or change their health care management (11%). CONCLUSIONS: The
      Australian prevalence of online health seekers is likely to be slightly higher
      than 21%. IMPLICATIONS: The Intemet can deliver preventative and clinical health
      information to a critical mass of Australians, but poorer and older Australians
      may be unable to access it.

PMID- 12054340
TI  - The mumps outbreak that wasn't.

PMID- 12054339
TI  - Undergraduate public health education: a workforce perspective.
AB  - OBJECTIVE: To describe the career paths of students who majored in public health
      at the undergraduate level and to assess the skills and knowledge these graduates
      believed were most useful to them in the public health workforce. METHOD: A
      telephone survey was conducted of all graduates from Adelaide University's
      Bachelor of Health Sciences degree from 1992-99 who had majored in public health
      (124 graduates). RESULTS: The response rate to the graduate survey was 71%. Using
      the definition of public health functions from the National Delphi Study on
      Public Health Functions to delineate the public health workforce, 59% of
      respondents were employed in public health. Graduates working in public health
      valued generic skills such as communication and collaboration more highly than
      more specific public health skills and knowledge areas. However, they also
      believed their undergraduate course would have been improved by a more practical
      orientation. CONCLUSIONS: A high proportion of graduates from this generalist
      degree who major in public health find employment in the public health workforce.
      They greatly value the generic skills associated with their undergraduate public
      health education and believe their entry into the workforce would have been
      further facilitated by stronger links between their academic program and the
      working environment of public health professionals. IMPLICATIONS: Studies of
      workforce training programs in public health must differentiate between the
      educational needs of undergraduate and postgraduate students. In particular,
      strategies need to be developed to provide stronger links between undergraduate
      students and the public health workforce.

PMID- 12054341
TI  - New Year quit smoking resolutions.

PMID- 12054343
TI  - Comment was made by an individual on refugees from Afghanistan.

PMID- 12054342
TI  - HIV seroconversion.

PMID- 12054344
TI  - Assessment of possible ecological risks and hazards of transgenic fish with
      implications for other sexually reproducing organisms.
AB  - Transgenic technology is developing rapidly; however, consumers and
      environmentalists remain wary of its safety for use in agriculture. Research is
      needed to ensure the safe use of transgenic technology and thus increase consumer
      confidence. This goal is best accomplished by using a thorough, unbiased
      examination of risks associated with agricultural biotechnology. In this paper,
      we review discussion on risk and extend our approach to predict risk. We also
      distinguish between the risk and hazard of transgenic organisms in natural
      environments. We define transgene risk as the probability a transgene will spread
      into natural conspecific populations and define hazard as the probability of
      species extinction, displacement, or ecosystem disruption given that the
      transgene has spread. Our methods primarily address risk relative to two types of
      hazards: extinction which has a high hazard, and invasion which has an unknown
      level of hazard, similar to that of an introduced exotic species. Our method of
      risk assessment is unique in that we concentrate on the six major fitness
      components of an organism's life cycle to determine if transgenic individuals
      differ in survival or reproductive capacity from wild type. Our approach then
      combines estimates of the net fitness parameters into a mathematical model to
      determine the fate of the transgene and the affected wild population. We also
      review aspects of fish ecology and behavior that contribute to risk and examine
      combinations of net fitness parameters which can lead to invasion and extinction
      hazards. We describe three new ways that a transgene could result in an
      extinction hazard: (1) when the transgene increases male mating success but
      reduces daily adult viability, (2) when the transgene increases adult viability
      but reduces male fertility, and (3) when the transgene increases both male mating
      success and adult viability but reduces male fertility. The last scenario is
      predicted to cause rapid extinction, thus it poses an extreme risk. Although we
      limit our discussion to aquacultural applications, our methods can easily be
      adapted to other sexually reproducing organisms with suitable adjustments of
      terminology.

PMID- 12054345
TI  - Human anti-rhesus D IgG1 antibody produced in transgenic plants.
AB  - Transgenic plants represent an alternative to cell culture systems for producing
      cheap and safe antibodies for diagnostic and therapeutic use. To evaluate the
      functional properties of a 'plantibody', we generated transgenic Arabidopsis
      plants expressing full-length human IgG1 against the Rhesus D antigen, which is
      responsible for alloimmunization of RhD- mothers carrying an RhD+ fetus. Anti-RhD
      extracted from plants specifically reacted with RhD+ cells in antiglobulin
      technique, and elicited a respiratory burst in human peripheral blood mononuclear
      cells. Plant-derived antibody had equivalent properties to CHO cell-produced anti
      RhD antibody, indicating its potential usefulness in diagnostic and therapeutic
      programs.

PMID- 12054346
TI  - Ectopic expression of the ets transcription factor ER81 in transgenic mouse
      mammary gland enhances both urokinase plasminogen activator and stromelysin-1
      transcription.
AB  - The PEA3 group members PEA3, ER81 and ERM, which are highly conserved
      transcription factors from the Ets family, are over-expressed in metastatic
      mammary tumors. In the current study, we present the characterization of a
      transgenic mouse strain which over-expresses ER81 in the mammary gland via the
      long terminal repeat of the mouse mammary tumor virus (LTR-MMTV). Although six
      genotypically positive transgenic lines were identified, only one expressed the
      ectopic transcript with an exclusive expression in the lactating and late
      pregnancy (18th day) mammary glands. No mammary tumor or mammary deregulation
      appeared after 2 years of ectopic ER81 expression following lactation. We then
      sought to identify ER81 target genes, and the urokinase plasminogen activator
      (uPA) and the stromelysin-1, two enzymes involved in extracellular matrix
      degradation, were found to be transcriptionally upregulated in lactating mammary
      glands over-expressing ER81. Since these enzymes are involved in metastasis, this
      murine model could be further used to enhance mammary cancer metastatic process
      by crossing these animals with mice carrying non-metastatic mammary tumors. We
      thus created a transgenic mouse model permitting the over-expression of a
      functionally active Ets transcription factor in the mammary gland without
      perturbing its development.

PMID- 12054347
TI  - A human CpG island randomly inserted into a plant genome is protected from
      methylation.
AB  - In vertebrate genomes the dinucleotide CpG is heavily methylated, except in CpG
      islands, which are normally unmethylated. It is not clear why the CpG islands are
      such poor substrates for DNA methyltransferase. Plant genomes display
      methylation, but otherwise the genomes of plants and animals represent two very
      divergent evolutionary lines. To gain a further understanding of the resistance
      of CpG islands to methylation, we introduced a human CpG island from the
      proteasome-like subunit I gene into the genome of the plant Arabidopsis thaliana.
      Our results show that prevention of methylation is an intrinsic property of CpG
      islands, recognized even if a human CpG island is transferred to a plant genome.
      Two different parts of the human CpG island - the promoter region/ first exon and
      exon 2-4 - both displayed resistance against methylation, but the promoter/ exon1
      construct seemed to be most resistant. In contrast, certain sites in a plant CpG
      rich region used as a control transgene were always methylated. The frequency of
      silencing of the adjacent nptII (KmR) gene in the human CpG constructs was lower
      than observed for the plant CpG-rich region. These results have implications for
      understanding DNA methylation, and for construction of vectors that will reduce
      transgene silencing.

PMID- 12054348
TI  - Efficient generation of alpha(1,3) galactosyltransferase knockout porcine fetal
      fibroblasts for nuclear transfer.
AB  - Pigs are currently considered the most likely source of organs for human
      xenotransplantation because of anatomical and physiological similarities to
      humans, and the relative ease with which they can be bred in large numbers. A
      severe form of rejection known as hyperacute rejection has been the major barrier
      to the use of xenografts. Generating transgenic pigs for organ transplantation is
      likely to involve precise genetic manipulation to ablate the alpha(1,3)
      galactosyltransferase (galT) gene. In contrast to the mouse, homologous
      recombination in livestock species to ablate genes is hampered by the inability
      to isolate functional embryonic stem cells. However, nuclear transfer using
      genetically targeted cultured somatic cells provides an alternative means to
      producing pigs deficient for galT. In this study we successfully produced galT+/-
      somatic porcine fetal fibroblasts using two approaches; positive negative
      selection (PNS) using an isogenic targeting construct, and with a promoterless
      vector using non-isogenic DNA.

PMID- 12054349
TI  - Expression of a 434:VP16 chimeric activator leads to high-level activation of
      gene expression in stable transformants of Arabidopsis.
AB  - The performance of an expression system based on a fusion of the bacteriophage
      434-repressor to the VP16 activation domain of Herpes simplex virus type 1
      (434:VP16) was tested after stable integration into Arabidopsis. A special
      feature of this system was the use of the monocot maize ubiquitin1 and rice
      actin1 promoters to drive the expression of the 434:VP16 activator and 434
      repressor, respectively. Our results demonstrate that the maize ubiquitin1 and
      the rice actin1 promoters, each of which contain introns, are active in
      Arabidopsis and can be used to express genes in this dicot species. Activation of
      gene expression after co-integration of the activator and reporter cassettes into
      the same genomic locus resulted in a higher activation level (84-fold activation)
      compared to crossing individual lines expressing only the activator or the
      operator reporter cassette alone (9-fold activation). Increasing the number of
      operator elements in the reporter cassette from 1 to 4 increased the activation
      level in cross-activated lines to an average of 281-fold with one combination of
      parental lines giving a 900-fold activation. Simultaneous expression of the 434
      repressor protein driven by the rice actin promoter resulted in a significant
      decrease in the 434:VP16 mediated reporter gene expression. Nevertheless, an
      overall induction via 434:VP16 was possible even in the presence of the 434
      repressor protein. This feature is important for genes which need to be
      absolutely repressed except under activating conditions. To our knowledge this
      investigation is the first report on the use of the 434:VP16 chimeric activator
      in an expression system in stably transformed plant lines.

PMID- 12054350
TI  - The expression of a mammalian proteinase inhibitor, bovine spleen trypsin
      inhibitor in tobacco and its effects on Helicoverpa armigera larvae.
AB  - The cDNA for bovine spleen trypsin inhibitor (SI), a homologue of bovine
      pancreatic trypsin inhibitor (BPTI), including the natural mammalian presequence
      was expressed in tobacco using Agrobacterium tumefaciens-mediated transformation.
      Stable expression required the N-terminal targeting signal presequence although
      subcellular localization was not proven. SI was found to exist as two forms, one
      coinciding with authentic BPTI on western blots and the second marginally larger
      due to retention of the C-terminal peptide. Both were retained on a trypsin
      agarose affinity gel and had inhibitory activity. Newly emergent leaves contained
      predominantly the large form whereas senescent leaves had little except the fully
      processed form present. Intermediate-aged leaves showed a gradual change
      indicating that a slow processing of the inhibitor peptide was occurring. The
      stability of SI was shown by the presence of protein at high levels in completely
      senescent leaves. Modifications to the cDNA (3' and 5' changes and minor codon
      changes) resulted in a 20-fold variation in expression. Expression of modified SI
      in transgenic tobacco leaves at 0.5% total soluble protein reduced both survival
      and growth of Helicoverpa armigera larvae feeding on leaves from the late first
      instar. In larvae surviving for 8 days, midgut trypsin activity was reduced in SI
      tobacco fed larvae, while chymotrypsin activity was increased. Activities of
      leucine aminopeptidase and elastase-like chymotrypsin remained unaltered. The use
      of SI as an insect resistance factor is discussed.

PMID- 12054351
TI  - Introduction and expression of a deregulated tobacco nitrate reductase gene in
      potato lead to highly reduced nitrate levels in transgenic tubers.
AB  - Twenty transformed Solanum tuberosum plants issued from five different varieties
      and carrying a chimeric tobacco nitrate reductase gene (a truncated tobacco Nia2
      coding sequence fused to the CaMV 35S promoter) were cultivated in field
      conditions at INRA Ploudaniel in 1999 and 2000. In 60% of the transgenic plants,
      the presence of the tobacco Nia2 transcript was detected by RT-PCR. These clones
      exhibited a drastic decrease in the nitrate content in tubers. Indeed the nitrate
      content decreased by about 95% in the tubers of transformed plants compared to
      nontransformed potato plants from the same variety. This decrease was correlated
      with a modified regulation of NR expression as revealed by a higher chlorate
      sensitivity of these transgenic lines. Two methods of nitrate content
      determination in tubers were also compared and were found to give similar
      results.

PMID- 12054352
TI  - Avidin expressed in transgenic tobacco leaves confers resistance to two noctuid
      pests, Helicoverpa armigera and Spodoptera litura.
AB  - Fertile transgenic tobacco plants with leaves expressing avidin in the vacuole
      have been produced and shown to halt growth and cause mortality in larvae of two
      noctuid lepidopterans, Helicoverpa armigera and Spodoptera litura. Late first
      instar H. armigera larvae and neonate (< 12-h-old) S. litura larvae placed on
      leaves excised from T0 tobacco expressing avidin at 3.1-4.6 microM (micromoles/kg
      of fresh leaf tissue) had very poor growth over their first 8 days on the leaves,
      significant numbers had died by days 11 or 12 and all were dead by day 22 (H.
      armigera) or day 25 (S. litura). Similar results were obtained when late first
      instar H. armigera larvae were placed on leaves from T1 plants expressing avidin
      at six different average concentrations, ranging from 3.7 to 17.3 microM. Two
      larvae on the lowest expressing leaves survived to pupation, but there was total
      mortality among the other groups and no relationship between avidin concentration
      and the effects on the larvae. Synergistic effects between avidin-expressing
      tobacco plants and a purified Bt toxin, Cry1Ba, were demonstrated. Late instar H.
      armigera larvae fed with leaves from T2 plants expressing avidin at average
      concentrations of either <5.3 or > 12.9 microM, and painted with Cry1Ba protein
      at a rate equivalent to an expression level of 0.5% of total leaf protein, died
      significantly faster than larvae given either of the two treatments alone. Larvae
      fed with avidin-expressing leaves painted with the protease inhibitor, aprotinin,
      at a rate equivalent to 1% of total leaf protein had mortality similar to those
      given avidin-leaves alone. There was no evidence of antagonism between these two
      proteins.

PMID- 12054353
TI  - Expression of biotin-binding proteins, avidin and streptavidin, in plant tissues
      using plant vacuolar targeting sequences.
AB  - Tobacco plants have been developed which constitutively express high levels of
      the biotin-binding proteins, avidin and streptavidin. These plants were
      phenotypically normal and produced fertile pollen and seeds. The transgene was
      expressed and its product located in the vacuoles of most cell types in the
      plants. Targeting was achieved by use of N-terminal vacuolar targeting sequences
      derived from potato proteinase inhibitors which are known to target
      constitutively to vacuoles in potato tubers and, under wound-induction, in tomato
      leaves. Avidin was located in protein body-like structures within the vacuole and
      transgene protein levels remained relatively constant throughout the lifetime of
      the leaf. We describe two chimeric constructs with similar levels of expression.
      One comprised a potato proteinase inhibitor I signal peptide cDNA sequence
      attached to an avidin cDNA and the second a potato proteinase inhibitor II signal
      peptide genomic sequence (including an intron) attached to a core streptavidin
      synthetic sequence. We were unable to regenerate plants when transformation used
      constructs lacking the targeting sequences. The highest levels observed (up to
      1.5% of total leaf protein) confirm the vacuole as the organelle of choice for
      stable storage of plant-toxic transgene products. The efficient targeting of
      these proteins did not result in any measured changes in plant biotin metabolism.

PMID- 12054354
TI  - The potential use of a viral coat protein gene as a transgene screening marker
      and multiple virus resistance of pepper plants coexpressing coat proteins of
      cucumber mosaic virus and tomato mosaic virus.
AB  - Transgenic pepper plants coexpressing coat proteins (CPs) of cucumber mosaic
      virus (CMV-Kor) and tomato mosaic virus (ToMV) were produced by Agrobacterium
      mediated transformation. To facilitate selection for positive transformants in
      transgenic peppers carrying an L gene, we developed a simple and effective
      screening procedure using hypersensitive response upon ToMV challenge
      inoculation. In this procedure, positive transformants could be clearly
      differentiated from the nontransformed plants. Transgenic pepper plants
      expressing the CP genes of both viruses were tested for resistance against CMV
      Kor and pepper mild mottle virus (PMMV). In most transgenic plants, viral
      propagation was substantially retarded when compared to the nontransgenic plants.
      These experiments demonstrate that our transgenic pepper plants might be a useful
      marker system for the transgene screening and useful for classical breeding
      programs of developing virus resistant hot pepper plants.

PMID- 12054355
TI  - Offspring derived from intracytoplasmic injection of transgenic rat sperm.
AB  - The objective of the present study was to produce rat offspring by
      intracytoplasmic sperm injection (ICSI) using a Piezo-driven micromanipulator.
      Transgenic male rats carrying a green fluorescent protein gene (GFP: homozygous)
      were used as sperm donors. The epididymal spermatozoa were suspended and
      sonicated in m-KRB medium and were frozen in the same medium at -20 degrees C
      until use. When the sperm heads were aspirated into injection pipettes 7-10
      microm in diameter and introduced into oocytes from the Wistar strain, no
      offspring resulted from the transfer of 59 eggs. In contrast, the sperm heads
      were hung on the tip of injection pipettes 2-4 microm in diameter and introduced
      into the oocytes, use of Piezo resulting in the production of 18 transgenic
      offspring carrying the GFP gene from 181 eggs transferred. The oocytes from the
      Sprague-Dawley strain also supported full-term development following ICSI with
      three offspring resulting from 163 transferred eggs. In an additional ICSI trial,
      spermatozoa from infertile transgenic rats carrying human lactalbumin with the
      thymidine kinase gene (LAC3: heterozygous) were used. The spermatozoa of the LAC3
      transgenic rats appeared to be defective and immotile because of the expression
      of thymidine kinase in the testes, and no ICSI offspring resulted from 218
      transferred eggs. These results suggest that ICSI is applicable in rats when
      Piezo-driven smaller pipettes are used to inject sperm heads together with a
      limited amount of the surrounding medium and that the ability of isolated sperm
      heads to participate in normal embryo development is maintained under the
      cryopreservation conditions employed.

PMID- 12054356
TI  - Genetic engineering: what are we fearing?

PMID- 12054358
TI  - LC-mS analysis of human urine specimens for 2-oxo-3-hydroxy LSD: method
      validation for potential interferants and stability study of 2-oxo-3-hydroxy LSD
      under various storage conditions.
AB  - 2-Oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD), a major LSD metabolite, has
      previously been demonstrated to be a superior marker for identifying LSD use
      compared with the parent drug, LSD. Specifically, O-H-LSD analyzed using liquid
      chromatography-mass spectrometry has been reported to be present in urine at
      concentrations 16 to 43 times greater than LSD. To further support forensic
      application of this procedure, the specificity of the assay was assessed using
      compounds that have structural and chemical properties similar to O-H-LSD, common
      over-the-counter products, prescription drugs and some of their metabolites, and
      other drugs of abuse. Of the wide range of compounds studied, none were found to
      interfere with the detection of O-H-LSD or the internal standard 2-oxo-3-hydroxy
      lysergic acid methyl propylamide. The stability of O-H-LSD was investigated from
      0 to 9 days at various temperatures, pH conditions, and exposures to fluorescent
      light. Additionally, the effect of long-term frozen storage and pH was
      investigated from 0 to 60 days. There was no significant loss of O-H-LSD under
      both refrigerated and frozen conditions within the normal human physiological pH
      range of urine (4.6-8.4). However, significant loss of O-H-LSD was observed in
      samples prepared at pH 4.6-8.4 and stored at room temperature or higher (24-50
      degrees C).

PMID- 12054357
TI  - Simple method of methylation for gas chromatographic analysis of S-benzyl-N
      acetylcysteine, a metabolite of toluene, in human urine.
AB  - A simplified method of methylation for the determination of urinary S-benzyl-N
      acetylcysteine (benzylmercapturic acid, SBAC), a metabolite of toluene, by gas
      chromatography (GC) was developed. Acidified urine samples (pH 2) were extracted
      once with ethyl acetate and then derivatized to methyl ester (ME) using HCl
      methanol. The optimum conditions for derivatization for SBAC and the internal
      standard (S-phenethyl-N-acetylcysteine) were reaction at 60 degrees C for 20 min.
      The SBAC-ME was measured by capillary GC. The calibration curve showed good
      linearity over the range of 0.2 to 5.0 mg/L (r = 0.986). This method was compared
      with a previously developed diazomethane methylation method for testing urine
      from subjects who had sniffed toluene. The values obtained by the two different
      methods were in good accordance. These results suggest that this technique for
      the methylation of SBAC by means of HCI-methanol is simpler and time-saving, thus
      making it feasible to determine SBAC and other mercapturic acids in urinary
      samples obtained from subjects who have been exposed to organic solvents.

PMID- 12054359
TI  - Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide.
AB  - This study compared the urinary excretion characteristics of ethyl glucuronide
      (EtG) with that of ethanol, with focus on the effect of water-induced diuresis.
      Six healthy volunteers ingested an ethanol dose of 0.5 g/kg (range 25.0-41.5 g)
      as 5% (v/v) beer in 30 min and the same volume of water after 3 h. Urine
      collections were made before starting the experiment and at timed intervals over
      31.5 h. The concentration of EtG was determined by an LC-MS method (LOQ = 0.1
      mg/L). The urine samples collected immediately before starting drinking were all
      negative for ethanol and EtG, thus confirming that the participants had not
      recently ingested alcohol. Intake of beer resulted in a marked increase in
      excreted urine volume and a concomitant drop in creatinine concentration. The
      concentration of ethanol peaked at a mean value of 17 mmol/L in the 1.5-h urine
      collection. Except for one subject, EtG was first detectable (range 0.9-5.5 mg/L)
      at 1 h. Intake of water at 3 h produced another increase in urine volume and a
      drop in creatinine. The ethanol concentration curve was not influenced by the
      water diuresis, whereas this caused a distinct drop in the EtG concentration.
      When EtG was expressed relative to the creatinine value, this ratio was seemingly
      not affected by the intake of water. The ethanol concentration returned to zero
      at 6.5 h, whereas EtG was still detectable for up to 22.5-31.5 h, albeit at low
      levels in the end (< 1 mg/l). Only about 0.02% of the administered dose of
      ethanol (on a molar basis) was recovered in the urine as EtG. The results
      demonstrated that EtG remains detectable in the urine for many hours after the
      ethanol itself has been eliminated. Moreover, it was possible to lower the
      concentration of EtG by drinking large amounts of water prior to voiding, whereas
      this strategy did not influence the EtG/creatinine ratio or the concentration of
      ethanol.

PMID- 12054360
TI  - An online automatic sample cleanup system for the quantitative detection of the
      benzene exposure biomarker S-phenylmercapturic acid in human urine by
      electrospray ionization tandem mass spectrometry.
AB  - An online automatic sample cleanup system was developed for use with electrospray
      ionization tandem mass spectrometry (ESI-MS-MS) for the quantitative detection of
      the benzene exposure biomarker S-phenylmercapturic acid (S-PMA) in human urine.
      The sample clean-up system was constructed with an autosampling device, a
      reversed-phase C18 trap cartridge, a two-position switching valve, and
      controlling computer software and hardware. The sample cleanup system was
      interfaced directly with the ESI source of a triple-stage-quadrupole MS using
      multiple reaction monitoring of negative product ions derived from S-PMA and the
      internal standard as the detection mode. The calibration curve was linear using
      human urine spiked at concentrations from 0.23 to 100 mg/L S-PMA (R2 = 0.997).
      The detection limit of the analytical system for neat S-PMA standard solution was
      0.04 microg/L, whereas the detection limit was estimated to be lower than 0.35
      microg/L for a urine matrix containing trace amounts of S-PMA. Without tedious
      manual sample cleanup procedures, the analytical system is fully automatic and
      therefore useful for high-throughput urinary S-PMA determination. With the
      selectivity and the sensitivity provided by MS-MS detection, the analytical
      system can be used for high-throughput and accurate determination of S-PMA levels
      in human urinary samples as a biomarker for benzene exposure.

PMID- 12054362
TI  - A simple method for the determination of ethylene-thiourea (ETU) in biological
      samples.
AB  - A direct, simple, and rapid high-performance liquid chromatographic method has
      been developed for the determination of ethylene-thiourea (ETU) in biological
      fluids. Samples were chromatographed on a Lichrosorb RP8 (5 pm) column after
      extraction with dichloromethane. The mobile phase was a mixture of
      hexane/isopropyl alcohol/ethyl alcohol (93:6:1 v/v) added with 0.6 mL/L
      butylamine. Detection was done with a UV detector set at 243 nm. This method was
      validated to standard criteria. Calibration curves for ETU in 100 microL of 0.9%
      saline, 500 microL plasma, and 10 mL urine were linear (r2 > 0.99) from 0.05 to
      30 microg/mL, 0.025 to 30 microg/mL, and 1 to 100 ng/mL, respectively. The lower
      limit of detection was 20 ng/mL in plasma, 25 ng/mL in 0.9% saline, and 0.5 ng/mL
      in urine.

PMID- 12054361
TI  - Detection of flunitrazepam and 7-aminoflunitrazepam in oral fluid after
      controlled administration of rohypnol.
AB  - Although administered as a short-acting hypnotic for sleeping disorders,
      flunitrazepam, often in combination with alcohol or other drugs, was one of the
      most frequently abused benzodiazepines over the last 10 years. It has been
      reported in cases of driving under the influence, and its use is associated with
      marked psychomotor impairment. Studies over the last five years have investigated
      the use of oral fluid as an alternative matrix to blood and urine, especially
      when non-intrusive and quick sampling procedures are important (e.g., screening
      for drugs of abuse at the roadside and screening and confirmatory workplace drug
      testing). In this study, Rohypnol (flunitrazepam) was administered to four
      healthy volunteers, and oral fluid samples were collected by spitting into a
      polypropylene tube at fixed times between 0 and 6 h after the intake of a tablet
      of 1 mg. A specific and very sensitive method was developed, both for
      flunitrazepam and for its main metabolite 7-aminoflunitrazepam, based on solid
      phase extraction of the oral fluid samples, stored at +4 degrees C, and gas
      chromatographic-mass spectrometric analyses using negative chemical ionization
      with methane as the ionization gas. The heptadeuterated parent compound and
      metabolite were used as internal standards. The respective limits of detection
      and quantitation were 0.05 microg/L and 0.1 microg/L for flunitrazepam, and 0.1
      and 0.15 microg/L for 7-aminoflunitrazepam. The parent drug could only be
      detected when the analyses were performed within 12-24 h after collection of the
      oral fluid samples or when 2% of NaF was added to the collection tubes. The
      stability of flunitrazepam in oral fluid was poor, even at +4 degrees C, when no
      NaF was added to the sample. In any case, concentrations remained below 1
      microg/L. The metabolite was detected in slightly higher concentrations, with or
      without the presence of NaF, reaching a maximum of 1-3 microg/L within 2-4 h
      after administration. In all cases the drug was detectable, but at extremely low
      concentrations, for 6 h after intake of a normal dose of Rohypnol and it will be
      an analytical challenge to come up with a sufficiently sensitive onsite test for
      low-dose benzodiazepines in oral fluid.

PMID- 12054363
TI  - Simultaneous determination of cardenolides by sonic spray ionization liquid
      chromatography-ion trap mass spectrometry--a fatal case of oleander poisoning.
AB  - Simultaneous determination of oleandrin and its three related compounds,
      desacetyloleandrin, oleandrigenin, and gitoxigenin in blood by using liquid
      chromatography-three-dimensional quadrupole mass spectrometry (LC-3DQMS) system
      equipped with sonic spray ionization (SSI) interface was conducted. This
      analyzing method was suitable for all of these compounds except gitoxigenin. The
      limits of detection of oleandrigenin and desacetyloleandrin from blood were 2
      ng/mL and that of oleandrin was 3 ng/mL. The calibration curves for oleandrin,
      desacetyloleandrin, and oleandrigenin were linear in the range of 5-100 ng/mL.
      The coefficients of variation of oleandrin, desacetyloleandrin, and oleandrigenin
      in the blood were satisfactory ranging from 1.6% to 4.1%. This analysis method
      was applied to a fatal case of oleander poisoning. As a result of liquid
      chromatography-mass spectrometry (LC-MS) analysis, oleandrin was detected in
      heart blood and cerebrospinal fluid. Desacetyloleandrin, oleandrigenin, and
      gitoxigenin were not detected. In order to make identification of oleandrin
      reliable, LC-MS-MS analysis was performed. The concentrations of oleandrin found
      in the heart blood and cerebrospinal fluid were 9.8 and 10.1 ng/mL, respectively.

PMID- 12054364
TI  - Identification of 4-methylthioamphetamine and some of its metabolites in mouse
      urine by GC-MS after acute administration.

PMID- 12054365
TI  - Application of the CEDIA 6-MAM assay to routine drugs-of-abuse screening.
AB  - A total of 1010 urine specimens obtained from General Practitioners, drug
      dependency units, and hospitals throughout the West Midlands were screened using
      the Microgenics CEDIA 6-monoacetylmorphine (6-MAM) assay as a means of
      establishing its effectiveness as a screening technique to monitor heroin abuse.
      A total of 282 specimens screened positive for 6-MAM using the CEDIA 6-MAM assay.
      However, the presence of 6-MAM could not be confirmed by gas chromatography-mass
      spectrometry in 21 (7%) of the CEDIA-positive specimens. Morphine was identified
      in all of these specimens at free concentrations ranging between 410 microg/L to
      2010 microg/L. The data presented from this preliminary investigation suggests
      that either there are substances present within the urine specimens, as yet
      undetermined, which are interfering with the assay or that there may be a greater
      degree of cross reactivity to other opiates than previously published. 6-MAM
      assays may be potentially useful rapid screening techniques for high-throughput
      drugs-of-abuse screening laboratories performing employment and pre-employment
      screening. However, all positive results will still need to be confirmed by a
      more sensitive and specific technique.

PMID- 12054366
TI  - Long-term stability of methadone in clinical plasma samples stored at -20 degrees
      C.

PMID- 12054367
TI  - Fatal overdosage with nefopam (Acupan).
AB  - This paper presents a fatality due to massive, intravenous self-administration of
      nefopam (Acupan), a non-opiate central analgesic, in a 37-year-old female.
      Nefopam was measured in various postmortem samples by means of high-pressure
      liquid chromatography coupled to mass spectrometry via an ionspray interface.
      Heart blood concentration was 4.38 microg/mL and exceeded by approximately 30
      times the highest therapeutic levels with the usual reservations concerning
      possible postmortem redistribution. This is only the third case of death
      following nefopam overdose reported in the literature.

PMID- 12054368
TI  - Differences in contact lens-induced responses in the corneas of Asian and non
      Asian subjects.
AB  - PURPOSE: To investigate ethnic differences in corneal endothelia bleb formation
      and corneal swelling during contact lens wear under closed-eye conditions, with
      the use of lenses of varying oxygen transmissibilities (Dk/L) in Asian and non
      Asian subjects METHODS: Asian and non-Asian contact-lens naive subjects were
      fitted with one of four different types of contact lenses at each 20-minute
      session. During lens wear, the eyelid was closed Endothelial bleb formation was
      determined by specular microscopy or confocal microscopy immediately on eye
      opening. Some Asian contact-lens naive subjects were asked to wear one of two
      types of lenses (Dk/L values of 24 and 175) on each eye for 1 hour Corneal
      swelling was determined immediately after opening of the eyes. RESULTS: Asian
      subjects had a significantly higher degree of endothelial bleb formation than the
      non-Asian population for all closed eye conditions, p=0.0001. There was no
      significant difference in endothelial bleb formation between closed eves with or
      without lenses in the non-Asian population. There was a significantly higher
      degree of bleb formation with low Dk/L lenses, < or = 40, compared to high Dk/L
      lenses, > or = 110, in Asian subjects, p=0.0001. CONCLUSIONS: There is a
      significant difference between Asian and non-Asian subjects in the corneal
      response to stress. Under a closed eyelid only contact lenses with very high
      levels of Dk/L do not cause cornea stress in Asian patients.

PMID- 12054369
TI  - Relationship of contact lenses, pregnancy, and herpes simplex virus.
AB  - Herpes simplex virus (HSV) is one of the most common causes of corneal infections
      in the world, affecting more than 500,000 people in the United States alone. HSV
      keratitis recurrences can occur with systemic immunosuppression. Pregnancy can
      resemble a modified state of immunosuppression resulting in an increased risk for
      HSV keratitis. This type of immunosuppression combined with contact lens wear may
      have an additive effect and increase the possibility of HSV recurrence. Despite
      the obvious correlation, there are no reported cases in the literature. A case of
      bilateral HSV keratitis in a pregnant contact lens wearer is presented with an
      explanation of the causes and possible treatment methods.

PMID- 12054370
TI  - Bacterial keratitis and inflammatory corneal reactions: possible relations to
      contact lens oxygen transmissibility: the Harold A. Stein Lectureship 2001.
AB  - PURPOSE: Conventional contact lenses, particularly when used for extended wear
      (EW), are still associated with a high incidence of microbial keratitis and
      inflammatory reactions. This article discusses the possible relationship of such
      complications to contact lens oxygen transmissibility (Dk/t). METHODS: The
      literature, including our own work, is reviewed in regard to the binding of
      bacteria to the corneal epithelium and receptors likely to be associated with
      such binding, as well as the incidence of microbial keratitis and inflammatory
      reactions, in relation to conventional, lower Dk/t contact lenses and new, high
      Dk/t soft silicone hydrogel lenses. RESULTS: Receptors for lectins and,
      presumably, for bacteria such as Pseudomonas aeruginosa on the surface of the
      corneal epithelium are exposed in significantly higher numbers after wear of low
      Dk/t contact lenses than after wear of higher Dk/t lenses; and binding of P.
      aeruginosa follows the same pattern. Thus, it seems that high Dk/t lenses may
      reduce the risk of microbial keratitis. Published results of clinical trials of
      high Dk/t soft silicone hydrogel lenses worn for 7-day EW or 30-day continuous
      wear (CW), including our own 1-year study of 504 patients, are promising in so
      far as no cases of bacterial keratitis have yet been reported. In our study of
      high Dk/t silicone hydrogels, the incidence of inflammatory reactions, such as
      sterile infiltrates, was significantly lower than in studies of conventional soft
      lenses. Thus, it may be possible that inflammatory reactions also are related to
      oxygen transmissibility. CONCLUSIONS: High Dk/t contact lenses seem to reduce the
      rate of complications.

PMID- 12054371
TI  - Nocardia asteroides sclerokeratitis in a contact lens wearer.
AB  - PURPOSE: To report a case of sclerokeratitis caused by Nocardia asteroides in a
      soft contact lens wearer. CASE REPORT: A 65-year-old male presented with a 2
      month history of a corneal ulcer in the left eye. He wore two weekly disposable
      soft contact lenses on an extended basis. He revealed his history of gardening
      before the onset of symptoms. On examination, his best-corrected visual acuity
      was 20/30 in the right eye and 20/400 in the left eye. In the left eye, there was
      conjunctival injection. His cornea showed multiple patchy infiltrates, with a
      feathery border that was raised and involved up to the midstroma. There was a 3+
      anterior chamber reaction. Corneal scrapings were performed for smears and
      cultures. Topical 2% amikacin sulfate every half hour along with oral
      clarithromycin therapy was initiated. On follow-up, the sclera lesions worsened.
      RESULTS: Smears of corneal scrapings revealed gram-positive filamentous bacteria
      in Gram's stain. The cultures grew Nocardia asteroides. The patient was switched
      to trimethoprim-sulfamethoxazole (Bactrim DS, Roche Laboratories, Nutley, NJ) as
      the sclera was involved. The patient responded to treatment, and the infection
      resolved. When last seen, approximately 4 months after his initial presentation
      to us, his visual acuity was 20/40 in the affected eye. There was corneal
      scarring, and the adjacent sclera showed thinning. CONCLUSIONS: Nocardia
      sclerokeratitis can be associated with contact lens wear. Nocardia should be
      considered in the differential diagnosis of a corneal ulcer with an indolent
      progressive course with feathery infiltrates. Topical amikacin and systemic
      trimethoprim-sulfamethoxazole are effective drugs in the treatment of nocardial
      corneal infection with scleral involvement.

PMID- 12054372
TI  - Herpes simplex reactivation following laser in situ keratomileusis and subsequent
      corneal perforation.
AB  - PURPOSE: To present a case of corneal perforation secondary to herpes simplex
      reactivation after laser in situ keratomileusis (LASIK) and its subsequent
      management. METHODSL A case report of a 69-year-old man who underwent LASIK after
      penetrating keratoplasty for herpes simplex keratitis (HSK) is presented.
      RESULTS: The patient is a 69-year-old man who had a penetrating keratoplasty of
      the right eye 6 years prior for corneal scarring secondary to HSK. A spectacle
      refraction of -13.25 + 6.00 x 45 yielded 20/60 visual acuity in his grafted eye.
      LASIK was performed, and the patient's visual acuity without correction on
      postoperative day 1 was 20/60. Ten days after LASIK, the patient developed
      thinning of the cornea at the temporal edge of the flap, which perforated the
      following day. The perforation site was glued with cyanoacrylate adhesive and
      covered with a soft contact lens. After 7 months, a 4-mm lamellar keratoplasty
      and conjunctivoplasty was performed. Nine months after surgery, the patient's
      visual acuity without correction is 20/50 and the graft remains intact.
      CONCLUSION: Herpes simplex keratitis may be a contraindication for LASIK in
      postkeratoplasty patients. Bandage contact lenses and cyanoacrylate adhesive can
      be used successfully to manage the rare complication of corneal perforation after
      LASIK.

PMID- 12054373
TI  - Protection of the ocular surface after keratoprosthesis surgery: the role of soft
      contact lenses.
AB  - PURPOSE: To evaluate the short-term therapeutic value of soft contact lenses in
      patients with keratoprosthesis. METHODS: Nineteen patients with a collar button
      shaped keratoprosthesis were fitted with a soft contract lens and evaluated for
      the protective effect on the surrounding cornea. RESULTS: The lenses were found
      to be highly protective against evaporative damage to the corneal surface around
      the device. They were well tolerated and could remain clean and in place for
      months. One infection occurred. CONCLUSION: A soft contact lens can be of
      considerable protective value to the cornea surrounding a keratoprosthesis.

PMID- 12054374
TI  - Epidermolysis bullosa in a child.
AB  - PURPOSE: To describe a rare case of epidermolysis bullosa (EB) and its ocular
      manifestations. METHOD: A case report. RESULTS: The ocular and systemic findings
      in this dermatologic condition are presented. CONCLUSIONS: The various
      presentations of EB are discussed. The management requires close observation and
      treatment by both ophthalmology and dermatology. Unfortunately in this case the
      patient was brought to this country after maturation of the visual system with a
      resultant poor visual outcome.

PMID- 12054375
TI  - Acute angle closure glaucoma secondary to a choroidal melanoma.
AB  - PURPOSE: Report a case of acute angle closure glaucoma secondary to a choroidal
      melanoma. METHODS: Case report of a 75-year-old woman who presented with acute
      angle closure glaucoma with bilateral narrow angles. After medical management
      with drops and peripheral laser iridotomies in both eyes, the pressure was
      controlled and the angles were noted to be open. This allowed safe dilation of
      the pupils to perform funduscopic examination. A large choroidal melanoma was
      noted in the eye with the acute angle closure attack. RESULTS: Dilated fundus
      exam after peripheral laser iridotomies revealed a choroidal melanoma as the
      cause for the acute angle closure glaucoma. CONCLUSION: It is important to do a
      thorough eye examination to rule out secondary causes of angle closure, such as a
      potentially life-threatening tumor, when a patient presents with acute angle
      closure glaucoma.

PMID- 12054376
TI  - Effect of variable tinted spectacle lenses on visual performance in control
      subjects.
AB  - PURPOSE: To evaluate quantitatively the effects of tinted spectacle lenses on
      visual performance in individuals without visual pathology. METHODS: Twenty-five
      subjects were assessed by measuring contrast sensitivity with and without glare.
      Gray, brown, yellow, green, purple, and blue lens tints were evaluated.
      Measurements were repeated with each lens tint and with a clear lens, and the
      order was counterbalanced within and between subjects. Glare was induced with a
      modified brightness acuity tester. RESULTS: All subjects demonstrated an increase
      in contrast thresholds under glare conditions for all lens tints. However, purple
      and blue lens tints resulted in the least amount of contrast threshold increase;
      the yellow lens tint resulted in the largest contrast threshold increase.
      CONCLUSIONS: Purple and blue lens tints may improve contrast sensitivity in
      control subjects under glare conditions.

PMID- 12054377
TI  - Effect of softperm lens wear on corneal thickness and topography: a comparison
      between keratoconic and normal corneae.
AB  - PURPOSE: Complications related to contact lens-induced anoxia in the keratoconic
      eye are well documented, but the underlying mechanisms are poorly understood.
      This study compared topographical changes in corneal thickness and anterior
      corneal radius following SoftPerm (Ciba Vision, Atlanta, GA) (rigid-and-soft
      combination) lens wear in a group of keratoconic and normal individuals. METHODS:
      Video keratoscopic (VKS) (EyeSys, Houston, TX) and ultrasonographic pachometry
      measurements were taken at nine ocular locations, at central, mid-peripheral, and
      peripheral corneal areas of keratoconic and normal subjects. Subjects were
      subsequently fitted with SoftPerm lenses and further measurements of corneal
      topography and thickness were noted after 1 day, 2 weeks, and 1 month of daily
      wear. RESULTS: Corneal thickness increased significantly in normal and
      keratoconic eyes following SoftPerm lens wear. Radius values obtained from the
      VKS measurements indicated that a significant and progressive degree of corneal
      flattening occurred for the keratoconic subjects at the 1-day, 2-week, and 1
      month intervals, in contrast to the normal group, whose corneal radii remained
      unchanged. CONCLUSIONS: Corneal swelling occurs in both normal and keratoconic
      corneas following SoftPerm lens wear. Differences in the apparent central edema
      response within the keratoconic group may relate to the ease with which these
      corneas may be molded by a rigid contact lens.

PMID- 12054378
TI  - Visual performance of a multi-zone bifocal and a progressive multifocal contact
      lens.
AB  - PURPOSE: This study measured the relative visual performance of two planned
      replacement soft contact lenses for presbyopic correction: a multi-zone bifocal
      (ACUVUE, Johnson & Johnson Vision Care, Jacksonville, FL) contact lens and a
      progressive multifocal (Focus Progressives, CIBA Vision, Duluth, GA) contact
      lens. METHODS: This was a randomized, double-masked, non-dispensing cross-over
      study. Visual performance was evaluated by log of minimal angle of resolution
      (LogMAR) measurement of visual acuity (VA) under a representative range of
      luminances (distance 250 candela[cd]/m2 and 2.5 cd/m2, near 250 cd/m2 and 50
      cd/m2) and contrasts (90% and 10%). The 45 presbyopic subjects were equally
      distributed in three subgroups according to spectacle addition: low presbyopia
      (+0.75D to +1.25D); medium presbyopia (+ 1.50D to + 1.75D); and high presbyopia
      (+2.00 to +2.50D). RESULTS: Statistically significant differences were found in
      overall distance VA (P<0.001; average of four luminance-contrast combinations)
      and low-luminance distance VA (P=0.004), which, in both cases, favored the multi
      zone bifocal lens design. For low presbyopes, the multi-zone bifocal design
      produced a significantly better visual performance (P=0.004) than did the
      progressive multifocal. Overall near VA was also significantly better (P<0.001)
      with the multi-zone bifocal lens. Differences in near VA were particularly marked
      in high-luminance conditions (high and low contrasts combined) and were
      statistically significant for all three presbyopic subgroups. CONCLUSIONS: Visual
      acuity performance with the multi-zone bifocal was superior overall to that
      achieved with the progressive multifocal design. This study suggests that having
      only one addition is detrimental to performance with the progressive multifocal
      lens, particularly for low presbyopes.

PMID- 12054379
TI  - Effect of frequent-replacement contact lenses on normal conjunctival flora.
AB  - PURPOSE: To evaluate the effect of frequent-replacement contact lenses (FRCL) on
      the normal conjunctival flora. METHODS: This study included 30 patients using
      FRCL for refractive errors only and 32 age-matched, healthy controls. All
      patients replaced their lenses every 3 to 4 weeks. The samples were taken from
      the lower fornix with a culture swab and incubated in blood agar. RESULTS:
      Staphylococcus epidermidis was the predominant organism found in the conjunctival
      samples in the two groups. In the FRCL group, 9 (30%) S. epidermidis, 3 (10%)
      Acinetobacter Iwoffii, and 2 (6.7%) Moraxella spp. were isolated from the
      conjunctival samples. In the control group, 7 (23.3%) S. epidermidis and 2 (6.7%)
      A. lwoffii were isolated from the conjunctival samples. There was no
      statistically significant difference between two groups (P > .05). CONCLUSION:
      Our results show that the normal conjunctival flora was not changed by the FRCL,
      but there was a nonsignificant increase in the bacterial population.

PMID- 12054380
TI  - A comparison of the effect of refresh plus and bion tears on dry eye symptoms and
      ocular surface health in myopic LASIK patients.
AB  - PURPOSE: To compare the effect of artificial tears (0.5% carboxymethylcellulose
      [CMC] in lactate buffer vs. 0.3% hydroxypropyl methylcellulose and 0.1% dextran
      in bicarbonate buffer [HPMC]) on the preservation of ocular surface health in
      postoperative laser in situ keratomileusis (LASIK) patients. METHODS:
      Nonrandomized, comparative, retrospective analysis of a clinical database.
      Patients (n = 519; 985 eyes) had undergone LASIK in a single refractive surgery
      center performed by a single surgeon using the same LASIK technique (Nidek EC5000
      laser and ACS keratome). Patients (n = 254) were given CMC (Refresh
      Plus/Cellufresh) or HPMC (Bion Tears) four times per day and were evaluated at
      presurgery, week 2, and months 1, 3, and 6. Included patients were those with
      complete clinical data through the month I follow-up visit. RESULTS: There were
      no significant between-group differences in any baseline variable. Following
      LASIK, fewer CMC patients (n = 111) reported dry eye symptoms than HPMC patients
      (n = 143) at the week 2 (13.5% vs. 30.8%; P = .001) and month 1 (19.8% vs. 38.5%;
      P = .001) follow-up visits. CMC patients also had significantly lower mean ocular
      surface staining scores than HPMC patients at week 2 (0.09 vs. 0.30; P = .015)
      and month 1 (0.05 vs. 0.28; P = .008). There were no between-group differences in
      either measure at months 3 or 6 (P < or = .728). CONCLUSIONS: CMC was more
      effective than HPMC in controlling dry eye symptoms and preserving ocular surface
      health in the immediate postoperative period in myopic post-LASIK patients,
      possibly due to the greater muco-adhesive properties of CMC. These results
      warrant further investigation as to the most effective postoperative LASIK
      lubricant.

PMID- 12054381
TI  - The contribution of sports science and sports medicine to the development of the
      Australian sports system.

PMID- 12054382
TI  - SMA statement the benefits and risks of exercise during pregnancy. Sport Medicine
      Australia.
AB  - There are numerous benefits to pregnant women of remaining active during
      pregnancy. These include improved weight control and maintenance of fitness.
      There may also be benefits in terms of reduced risk of development of gestational
      diabetes meilitus and improved psychological functioning. Moderate intensity
      aerobic exercise has been shown to be safe in pregnancy, with a number of studies
      now indicating that for trained athletes it may be possible to exercise at a
      higher level than is currently recommended by the American College of
      Obstetricians and Gynecologists. Studies of resistance training, incorporating
      moderate weights and avoiding maximal isometnc contractions, have shown no
      adverse outcomes. There may be benefits of increased strength and flexibility.
      The risk of neural tube defects due to exercise-induced hyperthermia that is
      suggested by animal studies is less likely in women, because of more effective
      mechanisms of heat dissipation in humans. There is accumulating evidence to
      suggest that participation in moderate intensity exercise throughout pregnancy
      may enhance birth weight, while more severe or frequent exercise, maintained for
      longer into the pregnancy: may result in lighter babies. There have been no
      reports of foetal injury or death in relation to trauma or contact during
      sporting activities. Despite this, a risk of severe blunt trauma is present in
      some sporting situations as pregnancy progresses. Exercise and lactation are
      compatible in the post-partum period, providing adequate calories are consumed.
      Considerations of pelvic floor function and type of delivery are relevant in
      planning a return to certain types of exercise at this time.

PMID- 12054383
TI  - Exercise in pregnancy: physiological basis of exercise prescription for the
      pregnant woman.
AB  - A pregnant woman participated in cycling events in the 2000 Olympics. Recently
      there was concern about the participation of a pregnant woman in the Australian
      netball team. More and more women are anxious to pursue sports during their
      pregnancies and to maintain condition. For the clinician or sports physician
      caring for women who want to maintain a high-level of physical activity there is
      no simple exercise prescription. It is probable that continuing exercise by women
      who are already conditioned will not result in foetal compromise, unless there
      are hidden or unknown complications of pregnancy. Pregnant women should probably
      exercise within limits that do not cause severe discomfort and should, as
      pregnancy progresses, be prepared to moderate the intensity and duration of their
      exercise programs to avoid risks and injury. It is probably not advisable for
      women to begin high intensity exercise programs when pregnant, although moderate
      exercise is beneficial to both mother and baby. The type of activity that is
      undertaken has to be taken into consideration and in particular the adverse
      effects of supine activity in late gestation recognised.

PMID- 12054384
TI  - The effects of vigorous exercise during pregnancy on birth weight.
AB  - Whether or not vigorous exercise during pregnancy affects birth weight is an
      important issue because birth weight is the single most important determinant of
      neonatal mortality. A current meta-analysis of randomised trials of exercise
      during pregnancy did not find, although also did not exclude, a clinically
      important effect of exercise on birth weight. Randomised trials may miss the
      women exercising at the most elite levels during pregnancy. We should remain open
      minded on this issue until sufficient evidence is available on which to base
      recommendations.

PMID- 12054385
TI  - The benefits of physical activity during pregnancy.
AB  - The aims of this paper are (1) to comment on the evidence relating to the health
      risks and benefits of physical activity (PA) for pregnant women and their unborn
      foetuses. and (2) to discuss the public health benefits of participation in
      appropriate physical activity during pregnancy. Evidence from recent original
      research and review papers suggests that there are potential benefits of
      appropriate PA in terms of maternal weight control and fitness, which are likely
      to have significant long term public health benefits. Concerns about the
      potential ill-effects of PA during pregnancy, such as hyperthermia, shortened
      gestational age and decreased birth weight are not supported by the most recent
      scientific reviews. The physiological adaptations to exercise during pregnancy
      appear to protect the foetus from potential harm and, while an upper level of
      safe activity has not been established, the benefits of continuing to be active
      during pregnancy appear to outweigh any potential risks. All decisions about
      participation in physical activity during pregnancy should however be made by
      women in consultation with their medical advisers.

PMID- 12054386
TI  - The risk of abdominal injury to women during sport.
AB  - Although trauma to pregnant women is a potential risk during sport, as there is
      no published information about the magnitude of this risk, it is presumed to be
      low. Whilst there is an emerging literature about the risk of adverse outcomes
      following severe and catastrophic trauma to pregnant women, this literature
      almost exclusively focuses on road trauma victims or the result of assault. This
      paper describes the risk of abdominal injuries to women participants across a
      range of sports in Australia. An extensive search of the available literature
      could not identify any studies that had discussed this issue specifically in
      pregnant women. Studies, which have reported injuries in athletes, have generally
      found abdominal/chest injuries to account for fewer than 2% of all injuries, even
      in contact sports. Most of these published studies do not differentiate between
      the chest and abdomen and provide no specfic details on the exact nature or
      mechanisms of the injuries. Given the limitations of the published studies, an
      examination of data from two Australian general injury databases (one describing
      hospital admissions, the other hospital emergency department presentations),
      three Australian sports-injury treatment databases (sports medicine clinic
      attendances and medical coverage services) and one cohort study was undertaken to
      describe sports-related abdominal injuries. These analyses confirm that the risk
      of abdominal injury during sport is very low. In conclusion, currently there is
      not an adequate evidence-base for quantifying the risk of abdominal injuries
      during sport in women, let alone pregnant women or for justifying a ban of sport
      on this basis. Recommendations for future epidemiological sports injury studies
      and the potential for linkages with perinatal morbidity and mortality databases
      are given.

PMID- 12054387
TI  - Pregnant athletes: a summary review of the legal issues.
AB  - This summary review is not, and should not be relied upon as, legal advice. It
      has been prepared at the request of the Journal of Science and Medicine in Sport
      as a discussion paper for the purposes of providing a background in the legal
      issues arising from the participation of pregnant women in sport. The discussion
      is necessarily pitched at a very general level, and without any specific
      circumstances in mind. Readers with particular concerns, or with specific issues
      to be addressed, should seek independent legal advice.

PMID- 12054388
TI  - Pregnancy in sport.

PMID- 12054389
TI  - Rehabilitative nursing: a core nursing function across all settings.
AB  - Nurses are challenged to meet the changing health care needs of the Australian
      population as they live longer and experience increasing levels of disability.
      This paper reports on part of the findings of a recent study of rehabilitation
      nurses and suggests that the findings are relevant to all nurses as they attempt
      to meet this challenge. Thirty-four registered nurses working in rehabilitation
      settings in three states of Australia participated in the study. In-depth
      interviews and focus group discussions were used to collect data and validate
      interpretations. From the seven domains of practice identified in the findings,
      this paper discusses only one, the rehabilitative approach. This domain begins to
      capture the how and why of rehabilitation nursing practice, rather than the what.
      The rehabilitative approach is about the way the nurses conceptualise and think
      about their practice and the people they interact with. It is greater than the
      cliche of holistic care. Given that rehabilitation is a process that the patient
      undergoes and is not setting specific, the findings of this study offer direction
      to all nurses in supporting the rehabilitation of their patients. The study, the
      first of its kind in Australia, provides valuable guidance for the designers of
      undergraduate and postgraduate nursing programs in Australia.

PMID- 12054390
TI  - Facets of private practice nursing: a conceptual model.
AB  - AIM: This paper critically examines the literature relating to private practice
      nursing. Particular attention is given to the reasons nurses choose private
      practice and the major issues involved. A conceptual model has been developed
      based on this information. BACKGROUND: Nurses' roles are expanding into different
      work domains. Private practice nursing is one of the advanced practice options
      available. It also requires the nurse to develop business knowledge and skills.
      METHODS: A literature search was conducted of Pub-Med, Cinahl, Medline and
      InfoTrac databases using the terms 'private practice', 'nurse entrepreneur',
      'nurses in business', Inurse practitioners', 'self-employed nurse', 'advanced
      practice' and 'clinical nurse specialist'. Further relevant articles were
      identified from the reference lists of papers detected by this literature search.
      In addition, conference proceedings were examined for any other material on this
      topic. FINDINGS: A thorough search of the existing literature revealed one
      unpublished theoretically based study which examined limited aspects of private
      practice nursing in Victoria. A reasonable number of articles and publications
      that provided anecdotal and personal accounts of being a nurse in business were
      identified. This review highlights the need for further theoretically based
      research in this area of nursing, so as to expand nursing knowledge. Suggestions
      are given for further research in this topical area. CONCLUSIONS/IMPLICATIONS:
      Existing research into private practice nursing is limited and not sufficient to
      inform changes to policy and nurse education. More research is needed.

PMID- 12054391
TI  - Life after breast cancer: Australian women's stories of support.
AB  - Quality support is crucial to the care of women diagnosed with breast cancer.
      Little qualitative research has been conducted in this area. Semi-structured
      interviews were conducted with six women in New South Wales, Australia, to
      explore their experiences of breast cancer. Specifically the study focused on the
      support the women felt they needed at different times during their illness
      experience, how this was given and by whom. The qualitative data from the
      interviews supported previous research in that the diagnosis of breast cancer was
      devastating. Their primary source of support was family and friends with their
      surgeon and general practitioner providing some support. Overall the women felt
      they received physical support. However, emotional support was lacking,
      especially from nurses.

PMID- 12054392
TI  - Evaluation of a mentor-arranged clinical practice placement for student nurses.
AB  - Second year nursing students evaluated a new initiative, the Mentor-Arranged
      Clinical Practice (MACP), which supplemented their other clinical experiences.
      Seventy-eight students (95.6%) returned their completed questionnaires. Results
      indicated that the MACP program was beneficial to the students in the acquisition
      of knowledge, improvement of basic nursing skills, time management,
      prioritisation in patient care, and improvement in their confidence and self
      esteem. Students identified six positive aspects of the MACP program: continuity
      and consolidation of nursing skills, improved communication and reporting skills,
      working in a variety of shifts, and working as a team member. Characteristics of
      a good mentor encompassed four areas: personality traits, teaching ability,
      nursing competence and interpersonal relationship. Findings suggest that there is
      a need for the development of mentorship models in the clinical experiences of
      undergraduate nursing courses, and the importance of effective clinical teachers
      in preparing nursing students for the workforce.

PMID- 12054393
TI  - Why nurses are resigning from rural and remote Queensland health facilities.
AB  - This paper presents a selection of the results reported in the study "Factors
      Influencing the Recruitment and Retention of Rural and Remote Area Nurses in
      Queensland" (Hegney et al 2001). The main aim of this study was to determine why
      nurses in those rura and remote areas of Queensland that reported higher than
      State average turnover rates between February 1999 and May 2000, chose to leave
      their employment. The study therefore investigated the factors that influenced
      nurses' decisions to leave rural and remote area practice, the factors that
      influenced them to remain in practice and those factors nurses considered
      irrelevant to leaving or staying in rural/remote area nursing. This paper reports
      those factors the participants believed influenced them to leave rural and remote
      area nursing in Queensland. While the findings cannot be generalised to the
      Australian nursing workforce or to nurses not employed by Queensland Health, the
      study does confirm the findings of prev ous Australian research and formulates
      recommendations to assist future nursing workforce planning and policy.

PMID- 12054394
TI  - Alcohol and other drug use is our business.

PMID- 12054395
TI  - Management of the child with fever.
AB  - The primary purpose of any intervention is to increase the child's comfort (or
      decrease their discomfort). The decision to treat fever therefore needs to be:
      individualised, based on knowledge of effectiveness, balanced against any risk of
      harm that might result from intervening. Interventions that assist the body's
      physiological responses to infection (eg encouraging fluids and removing excess
      clothing or wrappings) are particularly recommended.

PMID- 12054396
TI  - The challenges in providing quality clinical education for undergraduate nursing.

PMID- 12054397
TI  - Muriel Knox Doherty--recognised at the 'Treasures' exhibition in Canberra.

PMID- 12054398
TI  - Re: National drug policy: implications of the 'tough on drugs' ideology by
      Rosemary Norman.

PMID- 12054399
TI  - Appropriate use of images.

PMID- 12054400
TI  - Ways, means and ends: debating health care reform.

PMID- 12054401
TI  - Public health capacity in Canada.

PMID- 12054402
TI  - Coronary artery bypass grafting in octogenarians.

PMID- 12054403
TI  - Telehealth revisited.

PMID- 12054404
TI  - Disordered eating behaviours.

PMID- 12054405
TI  - Centralizing coronary artery bypass grafting surgery.

PMID- 12054406
TI  - A systematic review and meta-analysis of studies comparing mortality rates of
      private for-profit and private not-for-profit hospitals.
AB  - BACKGROUND: Canadians are engaged in an intense debate about the relative merits
      of private for-profit versus private not-for-profit health care delivery. To
      inform this debate, we undertook a systematic review and meta-analysis of studies
      comparing the mortality rates of private for-profit hospitals and those of
      private not-for-profit hospitals. METHODS: We identified studies through an
      electronic search of 11 bibliographical databases, our own files, consultation
      with experts, reference lists, PubMed and SciSearch. We masked the study results
      before determining study eligibility. Our eligibility criteria included
      observational studies or randomized controlled trials that compared private for
      profit and private not-for-profit hospitals. We excluded studies that evaluated
      mortality rates in hospitals with a particular profit status that subsequently
      converted to the other profit status. For each study, we calculated a relative
      risk of mortality for private for-profit hospitals relative to private not-for
      profit hospitals and pooled the studies of adult populations that included
      adjustment for potential confounders (e.g., teaching status, severity of illness)
      using a random effects model. RESULTS: Fifteen observational studies, involving
      more than 26 000 hospitals and 38 million patients, fulfilled the eligibility
      criteria. In the studies of adult populations, with adjustment for potential
      confounders, private for-profit hospitals were associated with an increased risk
      of death (relative risk [RR] 1.020, 95% confidence interval [CI] 1.003-1.038; p =
      0.02). The one perinatal study with adjustment for potential confounders also
      showed an increased risk of death in private for-profit hospitals (RR 1.095, 95%
      CI 1.050-1.141; p < 0.0001). INTERPRETATION: Our meta-analysis suggests that
      private for-profit ownership of hospitals, in comparison with private not-for
      profit ownership, results in a higher risk of death for patients.

PMID- 12054407
TI  - Weekly work hours and clinical activities of Canadian family physicians: results
      of the 1997/98 National Family Physician Survey of the College of Family
      Physicians of Canada.
AB  - BACKGROUND: Health systems planning is a challenging task, exacerbated by a lack
      of detailed information on the role played by family physicians, as indicated by
      practice variations across regions and demographic characteristics. Outcome
      measures used in past studies of family physician practice patterns were not
      uniform. Furthermore, past research has generally been limited to narrowly
      defined geographic regions. A national study of family physician practice
      patterns was undertaken to allow regional-level comparisons of clinical workload
      and range of medical services offered. METHODS: The 1997/98 National Family
      Physician Survey was mailed to a sample of 5198 Canadian family physicians and
      general practitioners (FP/GPs); the overall response rate was 58.4% (3036
      questionnaires returned, of which 3004 were analyzable). Sampling strata were
      based on College of Family Physicians of Canada (CFPC) membership status and
      regions of Canada. RESULTS: Clinical workload varied considerably across the
      demographic categories studied. Male physicians reported 8.9 more total weekly
      work hours than female physicians, but the mean number of medical and clinical
      services offered did not differ between the sexes. Solo practitioners reported
      53.8 (95% confidence interval [CI] 52.7-55.0) total weekly work hours, whereas
      those practising in multidisciplinary clinics reported 45.0 (95% CI 43.2-46.8)
      hours. FP/GPs in the Atlantic and Prairie provinces reported 5.6 and 5.1 more
      weekly work hours, respectively, than the national average of 51.4 (95% CI 50.8
      52.0) hours. Finally, FP/GPs who served inner-city populations reported 48.6 (95%
      CI 46.8-50.5) total weekly work hours, whereas those serving rural populations
      reported 57.0 (95% CI 54.7-59.2) hours. Mean weekly work hours were similar for
      all age cohorts less than 65 years. FP/GPs practising in less populated provinces
      and in rural areas reported the highest numbers of work hours, medical services
      offered and clinical procedures performed. INTERPRETATION: These data suggest
      significant variations in FP/GP clinical workload in relation to key demographic
      variables.

PMID- 12054408
TI  - Your money and/or your life?

PMID- 12054409
TI  - What price for-profit hospitals?

PMID- 12054410
TI  - The decline of family medicine as a career choice.

PMID- 12054411
TI  - The bog, the fog, the future: 5 strategies for renewing federalism in health
      care.

PMID- 12054412
TI  - Do bisphosphonates reduce the risk of osteoporotic fractures? An evaluation of
      the evidence to date.

PMID- 12054413
TI  - Identifying and managing adverse environmental health effects: 4. Pesticides.
AB  - Pesticide exposure can cause many different health effects, from acute problems
      such as dermatitis and asthma exacerbation to chronic problems such as chronic
      obstructive pulmonary disease and cancer. The resulting clinical presentations
      are undifferentiated, and specific knowledge of the links to environmental
      exposures is often required for effective diagnosis. In this article we
      illustrate the use of the CH2OPD2 mnemonic (Community, Home, Hobbies, Occupation,
      Personal habits, Drugs and Diet), a history-taking tool that assists physicians
      in quickly identifying possible environmental exposures. We also provide clinical
      information on the epidemiology, clinical presentations, treatment and prevention
      of pesticide exposures.

PMID- 12054414
TI  - Caring for refugees.

PMID- 12054415
TI  - A child with kinky hair.

PMID- 12054417
TI  - "This is brand new for us": FP residencies go begging as match ends.

PMID- 12054418
TI  - Graphic tobacco warnings having desired effect.

PMID- 12054420
TI  - Injection facilities needed to combat infection crisis, AIDS network says.

PMID- 12054419
TI  - Suicide claiming more British Falkland veterans than fighting did.

PMID- 12054421
TI  - With only your stethoscope and your brain.

PMID- 12054422
TI  - Occupational exposures to air contaminants at the World Trade Center disaster
      site--New York, September-October, 2001.
AB  - Amid concerns about the fires and suspected presence of toxic materials in the
      rubble pile following the collapse of the World Trade Center (WTC) buildings on
      September 11, 2001, the New York City Department of Health (NYCDOH) asked CDC for
      assistance in evaluating occupational exposures at the site. CDC's National
      Institute for Occupational Safety and Health (NIOSH) collected general area (GA)
      and personal breathing zone (PBZ) air samples for numerous potential air
      contaminants. This report summarizes the results of the assessment, which
      indicate that most exposures, including asbestos, did not exceed NIOSH
      recommended exposure limits (RELs) or Occupational Safety and Health
      Administration (OSHA) permissible exposure limits (PELs). One torch cutter was
      overexposed to cadmium; another worker was overexposed to carbon monoxide (CO)
      while cutting metal beams with an oxyacetylene torch or a gasoline-powered saw,
      and two more were possibly overexposed to CO. NIOSH recommended that workers
      ensure adequate on-site ventilation when using gas-powered equipment and use
      rechargeable, battery-powered equipment when possible.

PMID- 12054423
TI  - State-specific trends in self-reported blood pressure screening and high blood
      pressure--United States, 1991-1999.
AB  - High blood pressure (HBP) increases the risk for heart disease and stroke, the
      first and third leading causes of death in the United States, respectively. An
      estimated one in four U.S. adults has HBP, which is defined as taking
      antihypertensive medication or having either a systolic blood pressure (SBP) of >
      or = 140 mmHg or a diastolic blood pressure (DBP) of > or = 90 mmHg. Optimal
      blood pressure is defined as SBP of < or = 120 mmHg or DBP of < or = 80 mmHg. To
      reduce the prevalence of HBP in the United States, the National Heart, Lung, and
      Blood Institute initiated the National High Blood Pressure Education Program
      (NHBPEP) in 1972, recommending that all adults aged > or = 20 years have their
      blood pressure (BP) checked at least once every 2 years. Although HBP is easily
      detectable and can usually be controlled with treatment, greater awareness of BP
      levels among U.S. adults is needed. This report summarizes data from the
      Behavioral Risk Factor Surveillance System (BRFSS) on state-specific trends in
      recent BP screening and prevalence of HBP (both by self-report). The findings
      indicate that during 1991-1999, BP screening levels were very high, and the
      percent of adults reporting HBP increased among some populations. Innovative
      education and intervention programs are needed to prevent and treat HBP in five
      high-risk groups: men, blacks, Hispanics, persons with less education, and older
      adults.

PMID- 12054424
TI  - Nonfatal physical assault-related injuries treated in hospital emergency
      departments--United States, 2000.
AB  - CDC, in collaboration with the Consumer Product Safety Commission (CPSC),
      expanded CPSC's National Electronic Injury Surveillance System (NEISS) in July
      2000 to include all types and external causes of nonfatal injuries treated in
      U.S. hospital emergency departments (EDs). This ongoing surveillance system,
      called NEISS All Injury Program (NEISS-AIP), can be used to calculate national,
      annualized, weighted estimates for nonfatal injuries treated in U.S. hospital
      EDs. This report summarizes NEISS-AIP data, which indicate that approximately 1.6
      million persons were treated in U.S. EDs during 2000 for nonfatal physical (i.e.,
      nonsexual) assault-related injuries. Such injuries occurred disproportionately
      among males, adolescents, and young adults, particularly among black males; most
      of these injuries were contusions or lacerations, few of which resulted in
      hospital admission. NEISS-AIP data can increase understanding of physical assault
      related injuries and serve as a basis for monitoring trends, facilitating
      additional research, and evaluating intervention approaches.

PMID- 12054426
TI  - Detergent modulation of electron and proton transfer reactions in bovine
      cytochrome c oxidase.
AB  - The effect of detergents on electron and proton transfer in bovine cytochrome c
      oxidase was studied using steady-state and transient-state methods. Cytochrome c
      oxidase in lauryl maltoside has high maximal turnover (TN(max)=400 s(-1)),
      whereas activity is low (TN(max)=10 s(-1)) in Triton X-100. Single turnover
      studies of intramolecular electron transfer show similar rates in either
      detergent. Transient proton uptake experiments show the oxidase in lauryl
      maltoside consumes 1.8+/-0.3 H(+)/aa(3) during either partial reduction of the
      oxidase or reaction of fully reduced enzyme with O(2). However, the oxidase in
      Triton X-100 consumes 2.6+/-0.4 H(+)/aa(3) during partial reduction and 1.0+/-0.2
      H(+)/aa(3) in the O(2) reaction. Absorption spectra recorded during turnover show
      that the enzyme undergoes activation in lauryl maltoside, but does not activate
      in Triton X-100. We propose that cytochrome c oxidase in different detergents
      allows access to different sites of protonation, which in turn influences steady
      state activity.

PMID- 12054425
TI  - Evidence for involvement of calpain in c-Myc proteolysis in vivo.
AB  - Precise control of the level of c-Myc protein is important to normal cellular
      homeostasis, and this is accomplished in part by degradation through the
      ubiquitin-proteasome pathway. The calpains are a family of calcium-dependent
      proteases that play important roles in proteolysis of some proteins, and their
      possible participation in degradation of intracellular c-Myc was therefore
      investigated. Activation of calpain with the cell-permeable calcium ionophore
      A23187 in Rat1a-myc or ts85 cells in culture induced rapid cleavage of c-Myc.
      This degradation was both calpain- and calcium-dependent since it was inhibited
      by preincubation with either the calpain-inhibitory peptide calpeptin or the
      calcium-chelating agent EGTA. A23187-induced c-Myc cleavage occurred in a time
      dependent manner comparable to that of FAK, a known calpain substrate, and while
      calpeptin was able to significantly protect c-Myc from degradation, inhibitors of
      the proteasome or caspase proteases could not. Exposure of Rat1a-myc or ts85
      cells in culture to calpeptin, or to the thiol-protease inhibitor E64d, resulted
      in the accumulation of c-Myc protein without an impact on ubiquitin-protein
      conjugates. Using an in vitro assay, calpain-mediated degradation occurred
      rapidly with wild-type c-Myc as the substrate, but was significantly prolonged in
      some c-Myc mutants with increased transforming activity derived from lymphoma
      patients. Those mutants with a prolonged half-life in vitro were also more
      resistant to A23187-induced cleavage in intact cells. These studies support a
      role for calpain in the control of c-Myc levels in vivo, and suggest that
      mutations impacting on sensitivity to calpain may contribute to c-Myc-mediated
      tumorigenesis.

PMID- 12054427
TI  - Degradation of oxidized extracellular proteins by microglia.
AB  - In living organisms a permanent oxidation of protein oxidation occurs. The
      degradation of intracellular oxidized proteins is intensively studied, but
      knowledge about the fate of oxidatively modified extracellular proteins is still
      limited. We studied the fate of exogenously added oxidized proteins in microglial
      cells. Both primary microglial cells and RAW cells are able to remove added
      oxidized laminin and myelin basic protein from the extracellular environment.
      Moderately oxidized proteins are degraded most efficiently, whereas strongly
      oxidized proteins are taken up by the microglial cells without an efficient
      degradation. Activation of microglial cells enhances the selective recognition
      and degradation of moderately oxidized protein substrates by proteases. Inhibitor
      studies also revealed an involvement of the lysosomal and the proteasomal system
      in the degradation of extracellular proteins. These studies let us conclude that
      microglial cells are able to remove oxidized proteins from the extracellular
      environment in the brain.

PMID- 12054428
TI  - Diastereomeric ecdysteroids with a cyclic hemiacetal in the side chain produced
      by cytochrome P450 in hormonally resistant insect cells.
AB  - A microsomal cytochrome P450 from a cell line of the insect Chironomus tentans
      has been shown to hydroxylate the steroid hormone 20-hydroxyecdysone at C(26) to
      yield 20,26-dihydroxyecdysone, P1, which is further metabolized to P2 and P3.
      Based on (1)H NMR studies, acetonide formation and quantum chemical calculations,
      P2 and P3 represent novel slowly interconvertible geometrical isomers, occurring
      at a 3:1 ratio, presumably arising from hemiacetal formation between the 26
      aldehyde group and the 22R-hydroxyl group to build a tetrahydropyran ring in the
      side chain. The stereochemistry at C(26) was S in P2 (trans-diol) and R in P3
      (cis-diol), respectively. Both metabolites showed S configuration at C(25). With
      Chironomus cells, P2/P3 was inactive as both a hormonal agonist and antagonist,
      whereas 20,26-dihydroxyecdysone (P1) showed weak agonist activity. Thus,
      cytochrome P450-mediated inactivation of 20-hydroxyecdysone may be responsible
      for the hormonal insensitivity observed in some subclones of this cell line.

PMID- 12054429
TI  - Nitration of cytoskeletal proteins in the chicken embryo chorioallantoic
      membrane.
AB  - Protein tyrosine nitration is one of the post-translational modifications that
      alter the biological function of proteins. Two important mechanisms are involved:
      peroxynitrite formation and myeloperoxidase or eosinophil peroxidase (EPO)
      activity. In the present work we studied the nitration of proteins in the in vivo
      system of chicken embryo chorioallantoic membrane (CAM). 3-Nitrotyrosine was
      detected only in the insoluble fraction of the CAM homogenate. By
      immunoprecipitation, Western blot analysis, and double immunofluorescence, we
      identified two major polypeptides that were nitrated: actin and alpha-tubulin.
      Quantification of actin and alpha-tubulin nitration revealed that they are
      differentially nitrated during normal development of the chicken embryo CAM.
      After irradiation, although they were both increased, they required different
      time periods to return to the physiological levels of nitration. It seems that
      both peroxynitrite formation and EPO activity are involved in the in vivo
      tyrosine nitration of cytoskeletal proteins. These data suggest that tyrosine
      nitration of cytoskeletal proteins has a physiological role in vivo, which
      depends on the protein involved and is differentially regulated.

PMID- 12054431
TI  - Alteration of inhibitor selectivity by site-directed mutagenesis of Arg(294) in
      the ADP-glucose pyrophosphorylase from Anabaena PCC 7120.
AB  - Previous alanine scanning mutagenesis of ADP-glucose pyrophosphorylase from
      Anabaena PCC 7120 indicated that Arg(294) plays a role in inhibition by
      orthophosphate [J. Sheng, J. Preiss, Biochemistry 36 (1997) 13077]. In this
      study, analysis of several site-directed mutants in the presence of different
      metabolic effectors showed that the primary inhibitor for two of the mutant
      proteins, R294A and R294Q, was no longer orthophosphate but rather NADPH, which
      was a reversal in the pattern of inhibitor selectivity from the wild-type.
      Despite the differences in charge and size, analysis of the purified R294K,
      R294E, and R294Q mutant enzymes demonstrated similar decreases in orthophosphate
      affinity as the R294A mutant, while most of the other kinetic values were similar
      to those reported for the wild-type. All these results suggest that the positive
      charge of Arg(294) is not specifically involved in orthophosphate binding and
      that it is important in determining inhibitor selectivity.

PMID- 12054430
TI  - Vascular smooth muscle cell proliferation requires both p38 and BMK1 MAP kinases.
AB  - Vascular smooth muscle cell (VSMC) proliferation is a key event in the
      progression of atherosclerosis. Induction of both c-fos (through the
      transcription factor Elk-1) and c-jun, both immediate early genes, is important
      for the stimulation of VSMC proliferation and migration. It was earlier found
      that p38 mitogen-activated protein (MAP) kinase upregulates c-jun gene
      transcription through phosphorylation of two myocyte enhancer factor 2 (MEF2)
      family transcription factors, MEF2A and MEF2C, while big MAP kinase 1 (BMK1) may
      upregulate c-jun gene transcription through MEF2A, MEF2C, and also MEF2D. Here,
      we report that inhibition of BMK1 by a dominant negative form of MEK5 or
      pharmacologic inhibition of p38 by SB 203580 additively suppress serum-induced
      VSMC proliferation. This additive effect of p38 and BMK1 inhibition implies that
      these two kinases coordinately regulate MEF2 transcription factors. The exclusive
      activation of MEF2D by BMK1 appears required for this cooperative upregulation of
      c-jun in VSMC, and coactivation of p38 and BMK1 also has additive effects on the
      activation of a reporter gene linked to the c-jun promoter in our experimental
      system. Thus, coordinate activity of both the p38 and BMK1 pathways appears
      necessary for optimal transcription of c-jun and, pari pasu, VSMC proliferation.
      These results may have implications for the future design of pharmacologic agents
      for inhibition of VSMC growth.

PMID- 12054433
TI  - Comparative time-courses of copper-ion-mediated protein and lipid oxidation in
      low-density lipoprotein.
AB  - Free radicals damage both lipids and proteins and evidence has accumulated for
      the presence of both oxidised lipids and proteins in aged tissue samples as well
      as those from a variety of pathologies including atherosclerosis, diabetes, and
      Parkinson's disease. Oxidation of the protein and lipid moieties of low-density
      lipoprotein is of particular interest due to its potential role in the
      unregulated uptake of lipids and cholesterol by macrophages; this may contribute
      to the initial stage of foam cell formation in atherosclerosis. In the study
      reported here, we examined the comparative time-courses of lipid and protein
      oxidation during copper-ion-mediated oxidation of low-density lipoprotein. We
      show that there is an early, lipid-mediated loss of 40-50% of the Trp residues of
      the apoB100 protein. There is no comparable loss over an identical period during
      the copper-ion-mediated oxidation of lipid-free BSA. Concomitant with Trp loss,
      the antioxidant alpha-tocopherol is consumed with subsequent extensive lipid
      peroxidation. Further changes to the protein, including the copper-ion-dependent
      3.5-fold increase in 3,4-dihydroxyphenylalanine and the copper-ion-independent 3
      5-fold increase in o-tyrosine, oxidation products of Tyr and Phe, respectively,
      only occur after maximal lipid peroxidation. Long incubation periods result in
      depletion of 3,4-dihydroxyphenylalanine, presumably reflecting further oxidative
      changes. Overall, copper-ion-mediated oxidation of LDL appears to proceed
      initially by lipid radical-dependent processes, even though some of the earliest
      detectable changes occur on the apoB100 protein. This is followed by extensive
      lipid peroxidation and subsequent additional oxidation of aromatic residues on
      apoB100, though it is not yet clear whether this late protein oxidation is lipid
      dependent or occurs as a result of direct radical attack.

PMID- 12054432
TI  - ATA2-mediated amino acid uptake following partial hepatectomy is regulated by
      redistribution to the plasma membrane.
AB  - System A, the Na(+)-dependent amino acid transport activity, is encoded by the
      ATA2 gene and up-regulated following partial hepatectomy (PH), and its
      competitive inhibition interferes with liver regeneration. Rabbit polyclonal
      antibody was raised against a portion of the ATA2 gene product followed by
      immunodetection of ATA2 in isolated liver plasma membrane and lysate. The level
      of ATA2 increased in the plasma membrane following PH, while the relatively high
      quantity of ATA2 found in liver lysate remained constant. We also have shown that
      Northern analysis of steady-state ATA2 mRNA revealed no significant change
      following PH. These data show that ATA2-mediated transport is not regulated by
      the steady-state level of ATA2 mRNA but is regulated by the amount of ATA2 and
      redistribution to the plasma membrane. We hypothesize that ATA2 activity is
      regulated by recruitment of ATA2 protein from an intracellular compartment. In
      addition, the pattern of expression of System A activity in oocytes, transport
      kinetics, and sensitivity to chemical modification indicate the presence of a
      second System A isoform in liver that differs substantially from ATA2.

PMID- 12054434
TI  - Generation of multiple mRNA transcripts from the novel human apoptosis-inducing
      gene hap by alternative polyadenylation utilization and the translational
      activation function of 3' untranslated region.
AB  - hap, a novel human apoptosis-inducing gene, was identified to have two major mRNA
      species of 1.8 and 2.7 kb in length by Northern blot analysis of poly(A)(+) RNA
      from multiple human tissues. The two hap transcripts derive from the alternative
      polyadenylation site selection: an AATAAA signal at position 1528-1533 nt for the
      1.8 kb mRNA, and an AATAAA signal at position 2375-2380 nt for the 2.7 kb mRNA.
      The 3'-UTR spanning the region between the second and the third polyadenylation
      site of 2.7 kb hap was demonstrated to exert a translational activation function
      for hap itself and the reporter gene chloramphenicol acetyltransferase (CAT)
      expression by approximately threefold, despite no differences observed in the
      steady-state level of relative cytoplasmic mRNA. Comparing the mRNA stability of
      two hap transcripts indicated that the longer mRNA was not more stable than the
      short one. Taken together, all these data provide evidence that the hap 3'-UTR
      containing within the second and the third polyadenylation signal can regulate
      gene translation rather than transcription and mRNA stability.

PMID- 12054435
TI  - The multisubunit acetyl-CoA carboxylase is strongly associated with the
      chloroplast envelope through non-ionic interactions to the carboxyltransferase
      subunits.
AB  - The committed step for de novo fatty acid biosynthesis is the carboxylation of
      acetyl-CoA catalyzed by acetyl-CoA carboxylase (ACCase). Plastidial ACCase from
      most plants is a multisubunit complex composed of multiple copies of four
      different polypeptides, biotin carboxyl carrier protein (BCCP), biotin
      carboxylase (BC), and carboxyltransferase (alpha-CT and beta-CT). Immunoblot
      analyses revealed these four proteins were mostly (69% of total) associated with
      a 17,000 g insoluble fraction from lysed pea chloroplasts. Under the same
      conditions only 8% of ribulose-1,5-bisphosphate carboxylase was associated with
      this insoluble fraction. BCCP and biotin carboxylase BC subunits freely
      dissociated from 17 kg insoluble fractions under high ionic strength conditions,
      whereas alpha-CT and beta-CT subunits remained tightly associated. Both CT
      subunits were highly enriched in envelope versus stroma and thylakoid
      preparations whereas BC and BCCP subunits were predominantly stromal-localized
      due to partial dissociation. Rapid solubilization of intact chloroplasts with
      Triton X-100 followed by centrifugation at 30 kg resulted in a pellet that was up
      to 8-fold enriched in ACCase activity and 21-fold enriched in BC activity. Triton
      insoluble 30 kg pellets were reduced in lipid and chlorophyll content but
      enriched in chloroplast DNA due to the isolation of nucleoid particles. However,
      ACCase was not directly associated with nucleoids since enzymatic digestion of
      DNA or RNA had no effect on the association with Triton-insoluble matter. The
      amount of Triton-insoluble ACCase was similar in chloroplasts isolated from dark-
      or light-adapted leaves suggesting transitory starch granules were also not
      involved in this association. It is proposed that ACCase is associated with
      envelope membranes through interactions with an unidentified integral membrane
      protein.

PMID- 12054436
TI  - Purification and characterization of benzoate:coenzyme A ligase from Clarkia
      breweri.
AB  - Benzoate:CoA ligase (BZL) was partially purified from flowers of the annual
      California plant Clarkia breweri. BZL catalyzes the formation of benzoyl-CoA and
      anthraniloyl-CoA, important intermediates for subsequent acyltransferase
      reactions in plant secondary metabolism. The native enzyme is active as a monomer
      with a molecular mass of approximately 59-64.5 kDa, and it has K(m) values of 45,
      95, and 130 microM for benzoic acid, ATP, and CoA, respectively. BZL is most
      active in the pH range of 7.2-8.4, and its activity is strictly dependent on
      certain bivalent cations. BZL is an AMP-forming enzyme. Overall, its properties
      suggest that it is related to the family of CoA ligase enzymes that includes the
      plant enzyme 4-hydroxycinnamate:CoA ligase.

PMID- 12054437
TI  - Intracellular superoxide dismutase, catalase, and glutathione peroxidase
      activities and membrane lipid peroxide levels in Fusarium acuminatum upon
      environmental changes in a defined medium.
AB  - The variations of superoxide dismutase (SOD), catalase (CAT), and glutathione
      peroxidase (GSH-Px) activities and lipid peroxide (LPO) levels in Fusarium
      acuminatum, an aerobic filamentous fungus, were investigated depending on the
      carbon and nitrogen sources during the incubation period. Fungus was cultivated
      in growing medium containing either maltose or saccharose in 5-25 g/L
      concentration range as a carbon source and either glycine or peptone in 5-35 g/L
      concentration range as a nitrogen source at 28 degrees C and 100 rpm. The
      observed highest SOD, CAT, and GSH-Px activities were 31.2+/-0.655, 62.5+/-5.23,
      and 1.52+/-0.0122 IU/mg in the presence of 20 g/L maltose and 73.96+/-1.48,
      74.46+/-2.94, 3.48+/-0.083 IU/mg in the 15 g/L glycine-containing medium at 16
      days, respectively. At the same time, the minimum LPO level was observed at 20
      g/L maltose and 15 g/L glycine compared with the other carbon and nitrogen
      sources. The results showed a negative correlation between antioxidant enzyme
      activities and membrane LPO levels in F. acuminatum cells.

PMID- 12054438
TI  - Reduction of iron by extracellular iron reductases: implications for microbial
      iron acquisition.
AB  - The extracellular enzymatic reduction of iron by microorganisms has not been
      appropriately considered. In this study the reduction and release of iron from
      ferrioxamine were examined using extracellular microbial iron reductases and
      compared to iron mobilization by chemical reductants, and to chelation by EDTA
      and desferrioxamine. A flavin semiquinone was formed during the enzymatic
      reduction of ferrioxamine, which was consistent with the 1 e(-) reduction of iron
      by an enzyme. The rates for the enzymatic reactions were substantially faster
      than both the 2 e(-) chemical reductions and the chelation reactions. The rapid
      rates of the enzymatic reduction reactions demonstrated that these enzymes are
      capable of accomplishing the extracellular mobilization of iron required by
      microorganisms. The data suggest that mechanistically there are two phases for
      the mobilization and transport of iron by those microorganisms that produce both
      extracellular iron reductases and siderophores, with reduction being the
      principle pathway.

PMID- 12054440
TI  - A fluorescent-photochrome method for the quantitative characterization of solid
      phase antibody orientation.
AB  - A fluorescent-photochrome method of quantifying the orientation and surface
      density of solid phase antibodies is described. The method is based on
      measurements of quenching and rates of cis-trans photoisomerization and
      photodestruction of a stilbene-labeled hapten by a quencher in solution. These
      experimental parameters enable a quantitative description of the order of binding
      sites of antibodies immobilized on a surface and can be used to characterize the
      microviscosity and steric hindrance in the vicinity of the binding site.
      Furthermore, a theoretical method for the determination of the depth of immersion
      of the fluorescent label in a two-phase system was developed. The model exploits
      the concept of dynamic interactions and is based on the empirical dependence of
      parameters of static exchange interactions on distances between exchangeable
      centers. In the present work, anti-dinitrophenyl (DNP) antibodies and stilbene
      labeled DNP were used to investigate three different protein immobilization
      methods: physical adsorption, covalent binding, and the Langmuir-Blodgett
      technique.

PMID- 12054441
TI  - A novel ultraviolet assay for testing side reactions of carbodiimides.
AB  - Carbodiimides possess considerable absorbance in the ultraviolet region; the
      extinction coefficient of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) in
      water is epsilon(214) = 6.3. 10(3) L x mol(-1) x cm(-1). It provides a very
      simple method for testing possible side reactions of carbodiimides. This
      technique was used to study effects of pH, different buffers, and other
      components typically present in biological samples on EDC stability. It was shown
      that the hydrolysis rate in pure water increased from 1.5. 10(-5) to 5. 10(-4) s(
      1) by pH decreasing from 7 to 4. A strong increase of the rate of EDC loss was
      observed in the presence of different components. This effect can be described by
      the following row of hydrolysis rates: citrate >> acetate approximately phosphate
      >> SDS. The results can be used to optimize carbodiimide-mediated reactions of
      peptide bond formation in organic chemistry or peptide synthesis or during
      immobilization or cross-linking of biological molecules.

PMID- 12054442
TI  - Assay and analysis for anti- and pro-oxidative effects of ascorbic acid on DNA
      with the bulk acoustic wave impedance technique.
AB  - A bulk acoustic wave (BAW) impedance sensor has been applied for in situ
      monitoring of the whole process of DNA oxidative damage induced by the vitamin C
      (Vc)-Fe (III) system, based on its real-time responses to the density-viscosity
      change of the tested solution due to the damages occurring on the DNA molecules.
      The results showed that Vc exhibited two conflicting effects, i.e., pro-oxidation
      and anti-oxidation on the DNA at different Vc concentrations in the damage
      system, and the "threshold" concentration of Vc for these two effects was
      estimated to be about 100 micromol/L. The end-point frequency change of the
      sensor (Deltaf(m)) was found to be linearly related to the initial concentration
      of the soybean DNA (C(DNA)) in the range of 40-1000 microg/mL, and the
      exponential relationship between the frequency change (Deltaf(0)) vs damaging
      time suggested that the Fe (III)-mediated DNA damage by Vc could be described as
      a first-order kinetics reaction. The effects of variations in concentrations of
      Vc and Fe3+ on the DNA oxidative damage were discussed, and based on
      investigations for the enhancing influence of H2O2 and inhibiting influence of
      HO* scavengers on the DNA damage, the nature and physiological toxicity of the
      damage in biological system were also examined. In addition, UV-vis spectra and
      electrophoresis analysis were also used, and the experimental observations were
      in good agreement with the above results.

PMID- 12054443
TI  - Selective immobilization of multivalent ligands for surface plasmon resonance and
      fluorescence microscopy.
AB  - Cell surface multivalent ligands, such as proteoglycans and mucins, are often
      tethered by a single attachment point. In vitro, however, it is difficult to
      immobilize multivalent ligands at single sites due to their heterogeneity.
      Moreover, multivalent ligands often lack a single group with reactivity
      orthogonal to other functionality in the ligand. Biophysical analyses of
      multivalent ligand-receptor interactions would benefit from the availability of
      strategies for uniform immobilization of multivalent ligands. To this end, we
      report the design and synthesis of a multivalent ligand that has a single
      terminal orthogonal functional group and we demonstrate that this material can be
      selectively immobilized onto a surface suitable for surface plasmon resonance
      (SPR) experiments. The polymeric ligand we generated displays multiple copies of
      3,6-disulfogalactose, and it can bind to the cell adhesion molecules P- and L
      selectin. Using SPR measurements, we found that surfaces displaying our
      multivalent ligands bind specifically to P- and L-selectin. The affinities of P-
      and L-selectin for surfaces displaying the multivalent ligand are five- to
      sixfold better than the affinities for a surface modified with the corresponding
      monovalent ligand. In addition to binding soluble proteins, surfaces bearing
      immobilized polymers bound to cells displaying L-selectin. Cell binding was
      confirmed by visualizing adherent cells by fluorescence microscopy. Together, our
      results indicate that synthetic surfaces can be created by selective
      immobilization of multivalent ligands and that these surfaces are capable of
      binding soluble and cell-surface-associated receptors with high affinity.

PMID- 12054444
TI  - In vivo investigation of progressive alterations in rat mammary gland tumors by
      near-infrared spectroscopy.
AB  - We have investigated mammary gland tissues of female rats treated with 7,12
      dimethylbenz[a]anthracene in sesame oil by a near infrared (NIR) spectroscopy
      finding that the DNA and water contents in the cancerous tissues were larger than
      those in the normal tissues but that the lipid content in the former was less
      than that in the latter. With protein contents, however, little difference was
      observed between the two. Thus, we used a lipid band around 1725 nm (the first
      overtone of n-alkane) and a protein band around 2054 nm (a combination band of
      amide A and amide II of polypeptides) for a quantitative evaluation of malignant
      changes in the mammary gland tissues. The lipid/protein band intensity ratios
      were calculated from the spectra of the mammary glands in the control animals and
      those of the noncancerous and cancerous sites in the treated animals. The
      lipid/protein ratios in the control animals, in the noncancerous sites, and in
      the cancerous sites were 1.452 +/- 0.221 (n = 5), 0.728 +/- 0.069 (n = 5), and
      0.362 +/- 0.060 (n = 5), respectively. These values were significantly different
      from each other (P < 0.001). The lipid changes observed by near-infrared (NIR)
      spectroscopy were confirmed by the results obtained from chemical methods for the
      evaluation of lipid levels in the same samples. Thus, our NIR spectroscopic
      method would be able not only to discriminate between cancerous and normal
      tissues but also to distinguish animals with cancers from normal animals. In
      addition, as the cancer grew, the lipid band intensity decreased, this band was
      shifted to higher wavelengths, and collagen peaks appeared in the tissues. These
      findings were supported by histological examinations of the cancerous and normal
      tissues. The present study indicates that NIR spectroscopy has high specificity
      and sensitivity in discriminating cancerous tissues from normal mammary glands in
      animals and it may offer potential for noninvasive, in vivo diagnosis of female
      breast cancer in the near future.

PMID- 12054445
TI  - Time-resolved luminescence energy transfer immunobinding study using a ruthenium
      ligand complex as a donor label.
AB  - A novel immunosystem is described that exploits the effect of luminescence energy
      transfer from a luminescently labeled antigen to a fluorescent antibody. A
      luminescent ruthenium-ligand complex (D-455) with absorption/emission maxima at
      456/639 nm, respectively, was employed as the donor label, and a squaraine-type
      cyanine label (636/655 nm), as the fluorescent acceptor label. Specifically, the
      system human serum albumin (HSA)/anti-HSA was studied. HSA was labeled with the
      donor dye D-455, and anti-HSA was labeled with the acceptor dye A-631. On
      formation of the antigen-antibody complex, energy transfer occurs. The
      radiationless energy transfer affects both the decay time of D-455 and the
      intensities of the emissions of both D-455 and A-631. The decay time of around
      500 ns of D-455 allows frequency-domain measurements in the low kilohertz range
      and therefore can be based on the use of conventional optoelectronics. This also
      suggests gated measurements to be performed. The major difference from existing
      HSA immunosystems is the use of a slow decaying ruthenium-ligand complex as the
      donor and of a long-wave emitting cyanine acceptor dye having a high quantum
      yield and a decay kinetics that is governed by the rate of energy transfer from
      the slow decaying donor.

PMID- 12054446
TI  - Analysis of O-linked reducing oligosaccharides released by an in-line flow
      system.
AB  - Reducing O-linked oligosaccharides from bovine submaxillary mucin, bovine fetuin,
      and porcine gastric mucin were recovered by nonreductive alkaline beta
      elimination from an in-line flow system. Glycoproteins where attached to a solid
      support using hydrophobic interaction with alkali-resistant Poros reversed phase
      beads and a flow of alkali released the oligosaccharides. The alkali was
      subsequently neutralized by a continuous flow through cation exchange resin. The
      released oligosaccharides in the flow were trapped in a cartridge filled with
      graphitized carbon. Salt-free oligosaccharides could be recovered as a
      concentrated solution by elution with organic solvents from the cartridge. The
      glycosylation pattern of the released oligosaccharides was compared with the
      conventionally released and reduced oligosaccharides recovered from alkaline beta
      elimination in the presence of borohydride. In general, the recovery from the in
      line release was sometimes lower than from the reductive elimination method, but
      it was shown that alkaline degradation of reducing oligosaccharides was limited
      in this system. Liquid chromatography using graphitized carbon packing and high
      pH mobile phases together with negative ion electrospray mass spectrometry showed
      that both neutral and acidic reducing oligosaccharides could be analyzed in a
      single run. Reducing O-linked oligosaccharides could also be recovered in this
      way from human glycophorin separated by SDS-PAGE. The polyacrylamide was
      sufficient to retain the glycoprotein in the gel while the flow of alkali
      released the oligosaccharides. It was also shown that the alkaline conditions for
      releasing O-linked oligosaccharides from fetuin would partially release some N
      linked oligosaccharides, particularly in the presence of reducing agent.

PMID- 12054447
TI  - Evaluation of mitochondrial respiratory function in small biopsies of liver.
AB  - Mitochondrial respiratory function was studied in permeabilized pig liver
      biopsies. The cell membrane was permeabilized mechanically in tissue samples of 2
      7 mg, for application of a standardized substrate/inhibitor titration protocol in
      high-resolution respirometry. Specific respirometric tests demonstrated complete
      plasma membrane permeabilization and accessibility of substrates to intact
      mitochondria. High respiratory adenylate control ratios and cytochrome c
      conservation in the tissue preparation were comparable or even better than in
      isolated mitochondria. Citrate synthase and cytochrome c oxidase activities
      remained at 85% of controls after up to 98 h storage of liver tissue at 0 degrees
      C in histidine-tryptophan-ketoglutarate solution. Multiple mitochondrial defects,
      however, were indicated after 48 h cold storage by the decline in respiratory
      capacity, which was lowered to a larger extent with complex I substrates compared
      to respiration with substrates for complex II or IV, measured in the absence of
      cytochrome c. After prolonged ischemia, the adenylate control ratio was
      significantly reduced, and cytochrome c depletion was detected by the stimulatory
      effect of cytochrome c. High-resolution respirometry allows the assessment of
      mitochondrial function in a few milligrams of permeabilized liver tissue, without
      isolation of mitochondria. This provides a basis for the analysis of
      mitochondrial function in human liver biopsies.

PMID- 12054448
TI  - Measurement of Ca2+-binding constants of proteins and presentation of the
      CaLigator software.
AB  - The complexity of Ca2+ cell signaling is dependent on a plethoria of Ca2+-binding
      proteins that respond to signals in different ranges of Ca2+ concentrations.
      Since the function of these proteins is directly coupled to their Ca2+-binding
      properties, there is a need for accurately determined equilibrium Ca2+-binding
      constants. In this work we outline the experimental techniques available to
      determine Ca2+-binding constants in proteins, derive the models used to describe
      the binding, and present CaLigator, software for least-square fitting directly to
      the measured quantity. The use of the software is illustrated for Ca2+-binding
      data obtained for two deamidated forms of calbindin D(9k), either an isospartate
      56 (beta form) or a normal Asp-56 (alpha form). Here, the Ca2+-binding properties
      of the two isoforms have been studied using the chelator method. The alpha form
      shows similar Ca2+-binding properties to the wild type while the beta form has
      lost both cooperativety and affinity.

PMID- 12054449
TI  - Determination of 5-methyltetrahydrofolate (13C-labeled and unlabeled) in human
      plasma and urine by combined liquid chromatography mass spectrometry.
AB  - The association of folates with the prevention of neural tube defects and reduced
      risk of other chronic diseases has stimulated interest in the development of
      techniques for the study of their bioavailability in humans. Stable isotope
      protocols differentiate between oral and/or intravenous test doses of folate and
      natural levels of folate already present in the body. An liquid
      chromatography/mass spectrometry (LC/MS) procedure is described that has been
      validated for the determination of [13C]5-methyltetrahydropteroyl monoglutamic
      acid ([13C]5-CH3H4PteGlu) in plasma and urine, following oral dosing of
      volunteers with different labeled folates. Folate binding protein affinity
      columns were used for sample purification prior to LC/MS determination.
      Chromatographic separation was achieved using a Superspher 100RP18 (4 microm)
      column and mobile phase of 0.1 mol/L acetic acid (pH 3.3):acetonitrile (90:10;
      250 microL/min). Selected ion monitoring was conducted on the [M-H](-) ion: m/z
      458 and 459 for analyzing 5-CH3H4PteGlu; m/z 464 [M+6-H](-) to determine 5
      CH3H4PteGlu derived from the label dose; m/z 444 for analysis of 2H4PteGlu
      internal standard, and m/z 446 and 478 to confirm that there was no direct
      absorption of unmetabolized compounds. Calibration was linear over the range 0-9
      x 10(-9) mol/L; the limits of detection and quantification were 0.2 x 10(-9) and
      0.55 x 10(-9) mol/L, respectively. The mean coefficient of variation of the
      ratios (m/z 463/458) was 7.4%. The method has potential applications for other
      key folates involved in one-carbon metabolism.

PMID- 12054450
TI  - Generation of RNA aptamers to the G-protein-coupled receptor for neurotensin, NTS
      1.
AB  - G-protein-coupled receptors (GPCRs) are integral membrane proteins involved in
      signal transduction and constitute major drug targets for disease therapy.
      Aptamers, which are globular RNA or DNA molecules evolved to specifically bind a
      target, could represent a valuable tool with which to probe the role of such
      receptors in normal tissue and disease pathology and for cocrystallization with
      receptors for structure determination by X-ray crystallography. Using the
      bacterially expressed rat neurotensin receptor NTS-1 as an example, we describe a
      strategy for the generation of GPCR-specific RNA aptamers. Seven rounds of a
      "subtractive," paramagnetic bead-based selection protocol were used to enrich for
      neurotensin receptor-specific aptamers, while circumventing the evolution of
      aptamers reactive to minor protein contaminants. Representatives of each aptamer
      family were analyzed in Escherichia coli membrane nitrocellulose filter binding
      assays. Eight aptamers demonstrated specificity for the neurotensin receptor. One
      aptamer, P19, was characterized in detail and shown to bind to both the rat
      receptor and the human receptor with nanomolar affinity. P19 was also shown to
      interact with rat neurotensin receptor expressed in CHO cells, in both membrane
      preparations and intact cells. P19 represents the first example of a GPCR
      specific RNA aptamer.

PMID- 12054451
TI  - Quantification of splice variants using molecular beacon or scorpion primers.
AB  - Uncovering the relationship between the generation of alternative transcripts and
      cellular processes is of crucial importance in the exploration of a gene's
      biology. The description and quantification of the spatiotemporal splicing
      pattern can be one method to select the most interesting transcripts for future
      studies. Fluorescence-based real-time quantitative RT-PCR has recently
      revolutionized the possibilities for transcriptional quantification studies. In
      this report, Molecular Beacon and Scorpion probes have been tested as new
      possibilities for determining the expression level of alternative transcripts. We
      validated these systems by analyzing alternative splicing of exons 6, 15, and 16
      of the calpain 3 gene with tissues containing large variation in the ratio of the
      different transcripts. We determined conditions that demonstrated that boundary
      probes are useful tools and good alternatives to boundary primers, when
      developing a system to quantify specific transcripts. We suggest that the choice
      of a quantification system should depend in part on the structure and base
      composition of the gene and may have to be determined experimentally.

PMID- 12054452
TI  - Enhanced firefly bioluminescence assay of ATP in the presence of ATP extractants
      by using diethylaminoethyl-dextran.
AB  - A highly sensitive ATP bioluminescence assay with diethylaminoethyl-dextran (DEAE
      Dx) in the presence of ATP extractants such as trichloroacetic acid (TCA) and
      Triton X-100 is described. These ATP extractants inhibited the activity of
      firefly luciferase, resulting in a remarkable decrease in the intensity of light
      emission. However, DEAE-Dx enhanced the intensity of light emission as long as
      firefly luciferase was active in the presence of the ATP extractants. When DEAE
      Dx was used for the assay, the detection limits for ATP in the presence of TCA
      and Triton X-100 were 0.3 and 0.5 pM, respectively, in aqueous ATP standard
      solution. The detection limit in the presence of DEAE-Dx was improved 13- to 20
      fold compared to that in the absence of DEAE-Dx. The method was applied to the
      determination of ATP in Escherichia coli extracts. When a 5% solution of TCA was
      used for the extraction of ATP from E. coli cells, the detection limit
      corresponded to 250 cells ml(-1) of E. coli.

PMID- 12054453
TI  - A rapid screening method to monitor expression of recombinant proteins from
      various prokaryotic and eukaryotic expression systems using matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry.
AB  - Rapid methods using matrix-assisted laser desorption ionization-time-of-flight
      mass spectrometry to monitor recombinant protein expression from various
      prokaryotic and eukaryotic cell culture systems were devised. Intracellular as
      well as secreted proteins from both induced and constitutive expression systems
      were measured and monitored from whole cells and growth media, thus providing an
      alternative to time-consuming traditional methods for screening and monitoring of
      protein expression. The methods described here involve minimal processing of
      samples and are therefore relevant to high-throughput screening applications.

PMID- 12054454
TI  - Chemical ionization mass spectrometric determination of acrolein in human breast
      cancer cells.
AB  - A selected ion flow tube-chemical ionization mass spectrometric method is
      presented for the first determination of acrolein metabolically produced in
      biological tissues. Acrolein in aqueous samples (2.5 ml) is preconcentrated by
      distillation and directly analyzed using gas-phase proton transfer from H3O+.
      This method provides sensitive detection of acrolein with the method detection
      limit of 15 nM at the 99% confidence level. Detection is linear up to the highest
      concentration studied (13.5 microM, R2 = 0.998). Acrolein levels are determined
      in doxorubicin-sensitive (MCF-7) and doxorubicin-resistant (MCF-7/Adr) human
      breast cancer cells in vitro. The intracellular acrolein concentrations differ
      insignificantly: 0.61 microM for sensitive cells and 0.54 microM for resistant
      cells. Treatment with a physiological concentration of doxorubicin (0.5 microM)
      for 24 h at 37 degrees C increased acrolein levels by factors of 2.6 and 1.9 for
      MCF-7 and MCF-7/Adr cells, respectively. The differential enhancement observed is
      consistent with the lower levels of enzymes that neutralize oxidative stress in
      sensitive MCF-7 cells and overexpression of an active drug efflux pump P-170
      glycoprotein in resistant MCF-7/Adr cells.

PMID- 12054455
TI  - A melanocyte-keratinocyte coculture model to assess regulators of pigmentation in
      vitro.
AB  - Many melanocyte or skin equivalent models have been used to evaluate the
      potential efficacy of melanogenic compounds to regulate pigmentation, but there
      has been great variation in results, partially stemming from the use of different
      cell lines and diverse conditions for the melanogenic assays. In an earlier
      report, we optimized a microtiter format assay system to screen potential
      bioactive compounds using immortalized melan-a melanocytes. That assay system,
      termed the STOPR protocol, allowed effects on melanocyte proliferation and
      differentiation to be assessed in a highly sensitive, reproducible, and cost
      effective manner. However, in the skin and hair, melanocytes interact with
      keratinocytes, fibroblasts, and other cell types, and testing of putative
      bioactive compounds on melanocytes alone in culture does not allow one to observe
      the interactions with those other cell types, such as would occur in vivo.
      Therefore, we developed a melanocyte-keratinocyte coculture protocol that allows
      testing of compounds for potential effects on pigmentation in a more
      physiologically relevant context. It is a sensitive, reproducible, and reliable
      model for testing melanogenic regulators, and we have standardized it with known
      melanogenic inhibitors (hydroquinone, arbutin, kojic acid, and niacinamide) and
      stimulators (alpha-melanocyte-stimulating hormone, 8-methoxypsoralen, and 3,4
      dihydroxyphenylalanine). This coculture system allows for large-scale screening
      of candidate compounds in conjunction with the STOPR protocol and provides a more
      physiologically relevant system to study melanocyte-keratinocyte interactions and
      to elucidate the regulatory mechanisms of melanogenic compounds.

PMID- 12054456
TI  - High-performance liquid chromatographic technique for detection of a fluorescent
      analogue of ADP-ribose in isolated blood vessel preparations.
AB  - Analysis of endogenous nucleotides in biologic media is hampered by rapid
      degradation and low final concentrations that are difficult to detect. A reversed
      phase high-performance liquid chromatographic (HPLC) technique is described that
      efficiently detects a stable fluorescence derivative of adenosine 5'
      diphosphoribose (ADPR), 1,N6-etheno-ADPR (epsilon-ADPR), at low femtomolar
      concentration range in vascular tissue superfusates. epsilon-ADPR was formed by
      the reaction of ADPR with chloroacetaldehyde at 80 degrees C and pH 4.0. Gradient
      elution with 0.1 M KH2PO4 (pH 6.0), increasing methanol (0-35% over 18 min), and
      a 25-cm by 4.5-mm (5 microm) silica ODS-AM column were employed. epsilon-ADPR was
      detected by fluorescence at an excitation wavelength of 230 nm and an emission
      wavelength of 410 nm. The detection sensitivity for epsilon-ADPR was
      approximately 10 fmol. Linearity of the HPLC detection method was demonstrated in
      the range from 0.0125 to 1 pmol epsilon-ADPR. The method was validated in terms
      of within-day and between-day reproducibility of retention times and peak areas
      of standard nucleotide. Matrix-assisted laser desorption/ionization mass
      spectrometry measurements confirmed the presence of an etheno ring after reaction
      of ADPR with chloroacetaldehyde. The method was applied to quantitate the
      overflow of ADPR upon electrical field stimulation (8 Hz, 0.3 ms, 15 V, 1-2 min)
      of both canine and guinea-pig isolated mesenteric artery segments.

PMID- 12054457
TI  - Polyacrylamide gel electrophoresis without a stacking gel: application for
      separation of peptides.

PMID- 12054458
TI  - Recovery of cyanine-dye nucleotide triphosphates.

PMID- 12054459
TI  - pH-Stat titration allows the continuous determination of ribonuclease A activity
      toward cytidine 2',3'-cyclic monophosphate at high substrate concentrations.

PMID- 12054460
TI  - Magnetic beads capture assay for the study of zymogen activation.

PMID- 12054461
TI  - Determination of reducing sugars with 3-methyl-2-benzothiazolinonehydrazone.

PMID- 12054462
TI  - Canine sulfotransferase SULT1A1: molecular cloning, expression, and
      characterization.
AB  - Sulfotransferases (SULTs) are involved in detoxification and activation of
      various endogenous and exogenous compounds including important drugs and
      hormones. SULT1A, the phenol-SULT subfamily, is the most prominent subfamily in
      xenobiotic metabolism and has been found in several species, e.g., human, rat,
      and mouse. We have cloned a phenol-sulfating phenol SULT from dog (cSULT1A1) and
      expressed it in Escherichia coli for characterization. cSULT1A1 showed 85.8,
      82.7, 76.3, and 73.6% identities to human P-PST, human M-PST, rat PST-1, and
      mouse STp1, respectively. It consists of 295 amino acids, which is in agreement
      with the human ortholog and sulfate substrates typical for the SULT1A family,
      i.e., p-nitrophenol (PNP), alpha-naphthol, and dopamine. The K(m) for PNP was
      found to be within the nanomolar range. It also sulfates minoxidil and beta
      estradiol but not dehydroepiandrosterone. Western blot analysis indicated that
      this newly cloned enzyme was found to be ubiquitously expressed in canine tissues
      with highest expression in male and female liver.

PMID- 12054463
TI  - Further evidence for distinct reactive intermediates from nitroxyl and
      peroxynitrite: effects of buffer composition on the chemistry of Angeli's salt
      and synthetic peroxynitrite.
AB  - The nitroxyl (HNO) donor Angeli's salt (Na(2)N(2)O(3); AS) is cytotoxic in vitro,
      inducing double strand DNA breaks and base oxidation, yet may have
      pharmacological application in the treatment of cardiovascular disease. The
      chemical profiles of AS and synthetic peroxynitrite (ONOO(-)) in aerobic solution
      were recently compared, and AS was found to form a distinct reactive
      intermediate. However, similarities in the chemical behavior of the reactive
      nitrogen oxide species (RNOS) were apparent under certain conditions. Buffer
      composition was found to have a significant and unexpected impact on the observed
      chemistry of RNOS, and varied buffer conditions were utilized to further
      distinguish the chemical profiles elicited by the RNOS donors AS and synthetic
      ONOO(-). Addition of HEPES to the assay buffer significantly quenched oxidation
      of dihydrorhodamine (DHR), hydroxylation of benzoic acid (BA), and DNA damage by
      both AS and ONOO(-), and oxidation and nitration of hydroxyphenylacetic acid by
      ONOO(-). Additionally, H(2)O(2) was produced in a concentration-dependent manner
      from the interaction of HEPES with both the donor intermediates. Interestingly,
      clonogenic survival was not affected by HEPES, indicating that H(2)O(2) is not a
      contributing factor to in vitro cytotoxicity of AS. Variation in RNOS reactivity
      was dramatic with significantly higher relative affinity for the AS intermediate
      toward DHR, BA, DNA, and HEPES and increased production of H(2)O(2). Further, AS
      reacted to a significantly greater extent with the unprotonated amine form of
      HEPES while the interaction of ONOO(-) with HEPES was pH-independent. Addition of
      bicarbonate only altered ONOO(-) chemistry. This study emphasizes the importance
      of buffer composition on chemical outcome and thus on interpretation and provides
      further evidence that ONOO(-) is not an intermediate formed between the reaction
      of O(2) and HNO produced by AS.

PMID- 12054464
TI  - Diversity of properties among catalases.
AB  - Catalases from 16 different organisms including representatives from all three
      phylogenetic clades were purified and characterized to provide a comparative
      picture of their respective properties. Collectively the enzymes presented a
      diverse range of activities and properties. Specific activities ranged from
      20,700 to 273,800 units per milligram of protein and maximal turnover rates
      ranged from 54,000 to 833,000 per second. The effective concentrations of common
      catalase inhibitors, cyanide, azide, hydroxylamine, aminotriazole, and
      mercaptoethanol, varied over a 100- to 1000-fold concentration range, and a broad
      range of sensitivities to heat inactivation was observed. Michaelis-Menten
      kinetics were approximately followed only at the low substrate concentrations. At
      high H(2)O(2) concentrations, inactivation of small-subunit enzymes resulted in
      lower velocities than what were predicted, whereas large-subunit enzymes had
      velocities higher than predicted. Kinetic constants such as K(m) and V(max) for
      catalases must be labeled as "apparent."

PMID- 12054465
TI  - Functional and structural changes due to a serine to alanine mutation in the
      active-site flap of enolase.
AB  - Crystallographic and kinetic methods have been used to characterize a site
      specific variant of yeast enolase in which Ser 39 in the active-site flap has
      been changed to Ala. In the wild-type enzyme, the carbonyl and hydroxyl groups of
      Ser 39 chelate the second equivalent of divalent metal ion, effectively anchoring
      the flap over the fully liganded active site. With Mg(2+) as the activating
      cation, S39A enolase has <0.01% of wild-type activity as reported previously
      [J.M. Brewer, C.V. Glover, M.J. Holland, L. Lebioda, Biochim. Biophys. Acta 1383
      (2) (1998) 351-355]. Measurements of (2)H kinetic isotope effects indicate that
      the proton abstraction from 2-phosphoglycerate (2-PGA) is significantly rate
      determining. Analysis of the isotope effects provides information on the relative
      rates of formation and breakdown of the enolate intermediate. Moreover, assays
      with different species of divalent metal ions reveal that with S39A enolase
      (unlike the case of wild-type enolase), more electrophilic metal ions promote
      higher activities. The kinetic results with the S39A variant support the notions
      that a rate-limiting product release lowers the activity of wild-type enolase
      with more electrophilic metal ions and that the metal ions are used to acidify
      the C2-proton of 2-PGA. The S39A enolase was co-crystallized with Mg(2+) and the
      inhibitor phosphonoacetohydroxamate (PhAH). The structure was solved and refined
      at a resolution of 2.1 A. The structure confirms the conjecture that the active
      site flap is opened in the mutant protein. PhAH chelates to both Mg ions as in
      the corresponding structure of the wild-type complex. Positions of the side
      chains of catalytic groups, Lys 345 and Glu 211, and of "auxiliary" residues Glu
      168 and Lys 396 are virtually unchanged relative to the complex with the wild
      type protein. His 159, which hydrogen bonds to the phosphonate oxygens in the
      wild-type complex, is 5.7 A from the closest phosphonate oxygen, and the loop
      (154-166) containing His 159 is shifted away from the active center. A peripheral
      loop, Glu 251-Gly 275, also moves to open access to the active site.

PMID- 12054466
TI  - Heterologous expression and characterization of recombinant purple acid
      phosphatase from red kidney bean.
AB  - Purple acid phosphatases (PAPs) are dinuclear metallohydrolases of widespread
      occurrence. In a first step to understand structure-function relationship of PAP
      from red kidney bean (kbPAP), we cloned its cDNA and functionally expressed the
      enzyme in insect cells. kbPAP cDNA encodes a protein of 459 amino acids with 99%
      identity to the published primary structure (T. Klabunde et al., Eur. J. Biochem.
      226 (1994) 369-375). N-terminally the cDNA encodes 27 amino acids with
      characteristics for a signal directing the nascent protein to the endoplasmic
      reticulum. A baculovirus vector was constructed containing cDNAs of kbPAP and
      green fluorescent protein, the latter to serve as transfection and infection
      marker. Heterologous expression in High Five insect cells afforded a dimeric,
      disulfide-linked phosphatase of 110 kDa, identical to the mass of native kbPAP.
      Purification in three steps yielded 1.5 mg recombinant protein per liter of
      culture medium with a specific activity of 266 units/mg, slightly exceeding that
      of native kbPAP. The recombinant protein was functionally indistinguishable from
      native kbPAP, despite differences in glycosylation and sensitivity to redox
      reagents.

PMID- 12054467
TI  - Korormicin insensitivity in Vibrio alginolyticus is correlated with a single
      point mutation of Gly-140 in the NqrB subunit of the Na(+)-translocating NADH
      quinone reductase.
AB  - Na(+)-translocating NADH-quinone reductase (NQR) from the marine Vibrio
      alginolyticus is strongly inhibited by a new antibiotic korormicin. Korormicin
      specifically inhibits the Na(+)-dependent reaction of the NQR complex and acts as
      a purely non-competitive inhibitor for Q-1 with the inhibitor constant of 82 pM.
      Korormicin-resistant mutants were isolated from V. alginolyticus and the NQR
      complex was purified from a mutant KR2. Similar to 2-n-heptyl-4-hydroxyquinoline
      N-oxide (HQNO), korormicin acted as a purely noncompetitive inhibitor to the NQR
      complex from the mutant KR2, but the inhibitor constant increased to 8 microM,
      which is 10(5)-fold higher than that of the wild-type NQR complex. The inhibitor
      constant of HQNO, however, was only slightly affected by the acquisition of
      korormicin resistance. The spontaneous mutation was caused by a single mutation
      of G-422 to T-422 in the nucleotide sequence of the nqrB gene, which resulted in
      the conversion of Gly-140 to Val-140. Thus, Gly-140 seems to play an important
      role for the binding of korormicin to the NqrB subunit. The fact that korormicin
      is a purely noncompetitive inhibitor for Q-1 strongly supports the presence of
      one of Q-1 binding sites in the NqrB subunit, which also has a covalently bound
      FMN at Thr-235.

PMID- 12054468
TI  - Modulation of ANP-C receptor signaling by endothelin-1 in A-10 smooth muscle
      cells.
AB  - We have previously shown that pretreatment of A-10 smooth muscle cells (SMC) with
      angiotensin II (Ang II) attenuated atrial natriuretic peptide (ANP) receptor-C
      (ANP-C)-mediated inhibition of adenylyl cyclase without altering (125)I-ANP
      binding. In the present studies, we have investigated the modulation of ANP-C
      receptor signaling by endothelin-1 (ET-1). Pretreatment of A-10 SMC with ET-1 for
      24 h attenuated the expression of ANP-C receptor by about 60% as determined by
      immunoblotting which was reflected in attenuation of ANP-C-receptor-mediated
      inhibition of adenylyl cyclase. C-ANP(4-23)
      [des(Gln(18),Ser(19),Gln(20),Leu(21),Gly(22))ANP(4-23)-NH(2)], a ring-deleted
      peptide of ANP that interacts specifically with ANP-C receptor, inhibited
      adenylyl cyclase activity in a concentration-dependent manner with an apparent
      K(i) of about 1 nM in control cells. The maximal inhibition observed was about
      30% which was almost completely attenuated in ET-1-treated cells. In addition,
      Ang II- and oxotremorine-mediated inhibitions of adenylyl cyclase were also
      attenuated by ET-1 treatment; however, the expression of Gialpha-2 and Gialpha-3
      proteins and not of Gsalpha and Gbeta proteins was augmented by such treatment.
      The increased expression of Gialpha-2 and Gialpha-3 proteins by ET-1 treatment
      was inhibited by actinomycin D treatment (RNA synthesis inhibitor). On the other
      hand, the Gsalpha-mediated effects of some agonists on adenylyl cyclase activity
      were significantly decreased by ET-1 treatment. These results suggest that ET-1
      induced downregulation of ANP-C receptor and not the overexpression of Gi
      proteins may be responsible for the attenuation of C-ANP(4-23)-mediated
      inhibition of adenylyl cyclase activity. From these studies it may be suggested
      that the downregulation of ANP-C receptors by increased levels of endothelin in
      vivo may be one of the possible mechanisms for the pathophysiology of
      hypertension.

PMID- 12054469
TI  - Expression and regulation of the Na(+)/K(+)/2Cl(-) cotransporter NKCC1 in rat
      liver and human HuH-7 hepatoma cells.
AB  - The expression of sodium potassium chloride cotransporter 1 (NKCC1) was studied
      in different liver cell types. NKCC1 was found in rat liver parenchymal and
      sinusoidal endothelial cells and in human HuH-7 hepatoma cells. NKCC1 expression
      in rat hepatic stellate cells increased during culture-induced transformation in
      the myofibroblast-like phenotype. NKCC1 inhibition by bumetanide increased
      alpha(1)-smooth muscle actin expression in 2-day-cultured hepatic stellate cells
      but was without effect on basal and platelet-derived-growth-factor-induced
      proliferation of the 14-day-old cells. In perfused rat liver the NKCC1 made a
      major contribution to volume-regulatory K(+) uptake induced by hyperosmolarity.
      Long-term hyperosmotic treatment of HuH-7 cells by elevation of extracellular
      NaCl or raffinose concentration but not hyperosmotic urea or mannitol profoundly
      induced NKCC1 mRNA and protein expression. This was antagonized by the compatible
      organic osmolytes betaine or taurine. The data suggest a role of NKCC1 in
      stellate cell transformation, hepatic volume regulation, and long-term adaption
      to dehydrating conditions.

PMID- 12054470
TI  - The use of proteolysis to study the structure of nardilysin.
AB  - Treatment of a 128 kDa mouse nardilysin with trypsin initially produced an active
      105 kDa N-terminally cleaved form. Continued trypsin digestion occurred at the C
      terminus, producing inactive core species of approximately 92, 76.5, and 62 kDa.
      Protease V8 digestion generated a stable approximately 105 kDa form,
      nardilysin(V8), that was cleaved near the N-terminal trypsin site. The
      approximately 105 kDa nardilysin(V8) exhibited the same K(m) as did the uncleaved
      enzyme for substrates of the type Abz-GGFX(1)X(2)X(3)VGQ-EDDnp, where X residues
      were varied. However, k(cat) for nardilysin(V8) was 5-6 times greater. Both
      uncleaved nardilysin and nardilysin(V8) are inhibited by NaCl; however,
      nardilysin(V8) exhibits an IC(50) of approximately 2 mM compared to an IC(50) of
      approximately 50 mM for uncleaved nardilysin. Nardilysin(V8) is more sensitive to
      inhibition by phosphate buffer. Treatment of nardilysin(V8) with trypsin
      generated primarily the 92 kDa form which was inactive. Attempts to express
      nardilysin as a 105 kDa truncated N-terminal form or as a C-terminally truncated
      form led to inactive proteins.

PMID- 12054471
TI  - ATP stimulates glucose transport through activation of P2 purinergic receptors in
      C(2)C(12) skeletal muscle cells.
AB  - Extracellular ATP acts as a signal that regulates a variety of cellular processes
      via binding to P2 purinergic receptors (P2 receptors). We herein investigated the
      effects and signaling pathways of ATP on glucose uptake in C(2)C(12) skeletal
      muscle cells. ATP as well as P2 receptor agonists (ATP-gamma S) stimulated the
      rate of glucose uptake, while P2 receptor antagonists (suramin) inhibited the
      stimulatory effect of ATP, indicating that P2 receptors are involved. This ATP
      stimulated glucose transport was blocked by specific inhibitors of Gi protein
      (pertusiss toxin), phospholipase C (U73122), protein kinase C (GF109203X), and
      phosphatidylinositol (PI) 3-kinase (LY294002). ATP stimulated PI 3-kinase
      activity and P2 receptor antagonists blocked this activation. In C(2)C(12)
      myotubes expressing glucose transporter GLUT4, ATP increased basal and insulin
      stimulated glucose transport. Finally, ATP facilitated translocation of GLUT1 and
      GLUT4 into plasma membrane. These results together suggest that cells respond to
      extracellular ATP to increase glucose transport through P2 receptors.

PMID- 12054472
TI  - Biochemical implications of sequence comparisons of the cystic fibrosis
      transmembrane conductance regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride
      channel that is both of medical significance in humans and of interest with
      regard to osmoregulation in aquatic organisms. CFTR is composed of five domains:
      two membrane-spanning domains, two nucleotide-binding domains, and a regulatory
      domain. Notwithstanding the plethora of information concerning the structure and
      function of CFTR, the biochemistry of many facets of CFTR are not completely
      understood. In this regard, we have performed a sequence alignment of
      representative vertebrate CFTR with the aim of generating hypotheses on the
      functional significance of conserved and variable residues. Postulates on
      function common to all organisms are: (i) Thr338 in the sixth transmembrane
      segment could have a function related to that of the pore-lining residue Lys335,
      and it is possible that Thr338 hydrogen bonds to Lys335, thus indirectly
      affecting anion permeability; (ii) the fragment (111)PDNKE could be an ion
      sensor; (iii) motifs in the two nucleotide-binding domains reflect differential
      ATP binding and hydrolysis; and (iv) an interaction in the R domain involving
      (765)RRQSVL and the C terminal end of the domain results in an inhibitory
      conformation. Major adaptations in fishes include variations in the postulated
      ion sensor (111)PDNKE, and the absence of a proline residue in the R domain with
      consequent higher chloride efflux.

PMID- 12054473
TI  - Hydrogen peroxide-induced apoptosis of HL-60 human leukemia cells is mediated by
      the oxidants hypochlorous acid and chloramines.
AB  - We set out to identify whether HOCl, which is generated from H(2)O(2) /MPO/Cl(-),
      is a proximal mediator of H(2)O(2) programmed cell death in the HL-60 human
      leukemia cell. We found that authentic HOCl induces apoptosis in the HL-60 cell.
      Both the addition of methionine, an HOCl scavenger, and the removal of Cl(-) from
      the medium to prevent the formation of HOCl inhibited H(2)O(2)-induced apoptosis.
      HL-60 cells underwent apoptosis when exposed to HOCl in full medium, which gives
      rise to chloramines by the reaction of HOCl with amine groups, but not by HOCl in
      the amine-free HBSS, in which HOCl but not chloramines can be detected. Authentic
      chloramines induced apoptosis in this cell line in a concentration-dependent
      manner and at concentrations lower than HOCl. Full medium exposed to HOCl for 24
      h would support methionine noninhibitable apoptosis, but did not react with 2
      nitro-5-thiobenzoic acid (TNB), raising the possibility that the final inducer is
      a nonoxidant formed from HOCl and chloramines. We conclude that the signal for
      apoptosis induced by H(2)O(2) in the MPO-containing HL-60 cell involves the
      reaction of the diffusible oxidant HOCl with amines producing chloramines and a
      subsequent non-TNB-reactive product.

PMID- 12054474
TI  - Cloning of rat cytochrome P450RAI (CYP26) cDNA and regulation of its gene
      expression by all-trans-retinoic acid in vivo.
AB  - A novel retinoic acid (RA)-inducible cytochrome P450 (P450 RAI or CYP26),
      previously cloned from human, zebra fish, and mouse, functions in the metabolism
      of all-trans-RA to polar metabolites including 4-hydroxy-RA and 4-oxo-RA. To
      further study CYP26 in the rat model, we first cloned rat CYP26 cDNA. The
      nucleotide sequence predicts a 497-amino-acid protein whose sequence is 95%
      identical to mouse and 91% homologous to human CYP26. Animal studies showed that
      CYP26 mRNA expression is very low (0.01+/-0.008;P<0.05) in vitamin-A-deficient
      rats compared to pair-fed vitamin-A-sufficient rats (defined as 1.0). In a
      kinetic study, vitamin-A-deficient rats were treated with approximately 100
      microg of all-trans-RA and liver was collected after 3-72 h for analysis of CYP26
      mRNA by quantitative real-time PCR. Liver CYP26 mRNA increased to nearly 10-fold
      above control after 3 h (P<0.01), reaching a peak of about 2000-fold greater
      around 10 h (P<0.001) and then decreased rapidly. The CYP26 dose response to RA
      was nearly linear (R(2)=0.9638). Additionally, significant regulation of CYP26
      gene expression was observed in the vitamin-A-deficient, control, and RA-treated
      condition in lung, testis, and small intestine. We conclude that CYP26 mRNA
      expression is dynamically regulated in vivo by diet and RA in hepatic and
      extrahepatic tissues. The long-term down-regulation of CYP26 in retinoid
      deficiency may be critical for conserving RA, while the acute up-regulation of
      CYP26 may be important for preventing a deleterious overshoot of RA derived from
      either dietary or exogenous sources.

PMID- 12054475
TI  - The translation state of differentially expressed mRNAs in the hibernating 13
      lined ground squirrel (Spermophilus tridecemlineatus).
AB  - The translation state of differentially expressed mRNAs were compared in kidney
      and brown adipose tissue of the hibernating ground squirrel, Spermophilus
      tridecemlineatus. Polysome analysis revealed a striking disaggregation of
      polyribosomes during hibernation and the redistribution of Cox4 (cytochrome c
      oxidase subunit 4) and Oct2 (organic cation transporter type 2) transcripts into
      monosome and mRNP fractions of kidney cytoplasmic extracts. Additionally, OCT2
      protein levels decreased in kidney of hibernating animals in line with a strong
      decrease (85%) in translation rate compared with euthermic kidney. There was no
      translational depression in brown adipose tissue during hibernation and the H
      isoform of fatty-acid-binding protein (H-FABP), that is up-regulated during
      hibernation, was increasingly abundant in the heavy polyribosome fraction
      isolated from the brown adipose of hibernators. This may indicate the existence
      of a tissue-specific mechanism for the translational control of a subset of genes
      that are physiologically relevant to the survival of hibernation.

PMID- 12054476
TI  - Antioxidant enzyme activities, lipid peroxidation, and DNA oxidative damage: the
      effects of short-term voluntary wheel running.
AB  - We examined the effect of voluntary exercise on antioxidant enzyme activities
      (catalase, glutathione peroxidase, superoxide dismutase) in skeletal muscle (hind
      and forelimb) and heart of a model small mammal species: short-tailed field vole
      Microtus agrestis. In addition, DNA oxidation was determined in lymphocytes and
      hepatocytes using the comet assay and lipid peroxidation estimated in hindlimb
      muscle by measurement of thiobarbituric-acid-reactive substances. Voles
      (approximately 6 weeks old), exposed to a 16L:8D photoperiod (lights on 0500 h),
      ran almost continuously during darkness. We studied the effects of voluntary
      running over 1 or 7 days duration, with or without an 8-h rest period, on various
      biomarkers of oxidative stress compared to nonrunning controls. No differences
      were observed in antioxidant enzyme activities, except in heart total superoxide
      dismutase activity (P=0.037), with the lowest levels in 1- and 7-day runners at
      0500 h. DNA oxidative damage, in lymphocytes or hepatocytes, and lipid
      peroxidation did not differ between groups. There was no evidence of any
      significant increase in any oxidative stress parameter in running individuals,
      despite having significantly elevated energy expenditures compared to sedentary
      controls.

PMID- 12054477
TI  - Regulation of the murine alpha(2)(I) collagen promoter by retinoic acid and
      retinoid X receptors.
AB  - Retinoic acid decreases collagen production by hepatic stellate cells. This study
      investigated the effects of retinoic acid receptor beta (RARbeta) and retinoid X
      receptor alpha (RXRalpha) on the regulation of the alpha(2)(I) collagen promoter.
      Retinoic acid and the RARbeta and RXRalpha expression vectors suppressed the
      promoter in transfected stellate cells with maximal suppression obtained when
      combined. Mutation of the retinoic acid response element (RARE) at -879 to -874
      (site 1) enhanced promoter activity and diminished but did not eliminate the
      suppression by RARbeta and RXRalpha. Mutation of another RARE site (site 2), at 
      930 to -911, resulted in low activity that was inhibited by retinoic acid.
      Mutation of the AP-2-binding site enhanced promoter activity that was inhibited
      by retinoic acid. This study shows that the suppressive effect of retinoic acid
      on the promoter is maximal with a combination of RARbeta and RXRalpha and occurs
      at more than one RARE site. The effect of retinoic acid is not mediated by AP-2.

PMID- 12054478
TI  - Cell cycle specific changes in the human cyclin B1 gene regulatory region as
      revealed by response to trichostatin A.
AB  - The human cyclin Bl gene is cell cycle regulated with maximal activity during
      G(2)/M. We examined the role of histone deacetylation in cyclin Bl regulation
      using the histone deacetylase inhibitor trichostatin A (TSA). TSA treatment (100
      ng/ml) of NIH3T3 cells containing the luciferase reporter construct pCycB(-287)
      LUC caused an increase in promoter activity in G(0) and G(1) but no significant
      change in G(2). Removal of upstream sequences including an E-box and Sp1 site
      eliminated the TSA induced increase in G(0) and G(1), and caused a decrease in
      promoter activity during S and G(2). Promoter activity increased only 2-fold
      following TSA treatment of G(0) cells containing the construct pCycB(MUT-E-Box)
      LUC with an E-box mutation, and a decrease in activity was detected during G(2).
      We conclude that histone deacetylation contributes to the repression of cyclin B1
      expression in G(0) and G(1), and that this mechanism requires, in part, the E
      box. TSA reduction of cyclin B1 promoter activity in G(2), however, involves
      sequences within the first 119 bp. A working model for cyclin B1 regulation is
      provided.

PMID- 12054479
TI  - Hormone-stimulated Mg(2+) accumulation into rat hepatocytes: a pathway for rapid
      Mg(2+) and Ca(2+) redistribution.
AB  - Many diseases such as cardiac arrhythmia, diabetes, and chronic alcoholism are
      associated with a marked decrease of plasma and parenchymal Mg(2+), and Mg(2+)
      administration is routinely used therapeutically. This study uses isolated rat
      hepatocytes to ascertain if and under which conditions increases in extracellular
      Mg(2+) result in an increase in intracellular Mg(2+). In the absence of
      stimulation, changing extracellular Mg(2+) had no effect on total cellular Mg(2+)
      content. By contrast, carbachol or vasopressin administration promoted an
      accumulation of Mg(2+) that increased cellular Mg(2+) content by 13.2 and 11.8%,
      respectively, and stimulated Mg(2+) uptake was unaffected by the absence of
      extracellular Ca(2+). Mg(2+) efflux resulting from stimulation of alpha- or beta
      adrenergic receptors operated with a Mg(2+):Ca(2+) exchange ratio of 1. These
      data indicate that cellular Mg(2+) uptake can occur rapidly and in large amounts,
      through a process distinct from Mg(2+) release, but operating only upon specific
      hormonal stimulation.

PMID- 12054481
TI  - A 40-kDa polypeptide from papain digestion of the rabbit intestinal Na+/phosphate
      cotransporter retains Na+ and phosphate cotransport.
AB  - The rabbit intestinal brush border membrane Na+/phosphate cotransporter was
      digested with a variety of proteolytic enzymes. Limited papain digestion
      generated a 40-kDa polypeptide (P40) which retained putative substrate site
      markers, fluorescein isothiocyanatophenyl glyoxal and eosin n-acetyl imidazole.
      P40 retained Na+- and phosphate-selective tryptophan fluorescence quenching, pH
      sensitivity of ion-induced conformational changes, and tight Na+ and H(2)PO(4)(-)
      binding. Reconstituted into proteoliposomes, P40 catalyzed Na+-dependent
      phosphate uptake. The N-terminus of P40 was blocked. An internal sequence of P40
      demonstrated that it was derived from NaPi II b. These results suggest that P40
      may be a useful model system for studies of the molecular mechanism of Na+
      dependent phosphate cotransport and a starting point for structural studies.

PMID- 12054482
TI  - Polyenoic fatty acid isomerase from the marine alga Ptilota filicina: protein
      characterization and functional expression of the cloned cDNA.
AB  - The recently described enzyme, polyenoic fatty acid isomerase (PFI), from the
      marine alga Ptilota filicina J. Argardh has been analyzed with respect to its
      protein structure and an associated cofactor. The enzyme was purified to
      homogeneity (as judged by SDS-PAGE and silver staining). By sedimentation
      equilibrium ultracentrifugation the mass of the native enzyme was estimated to be
      125 kDa. The N-terminal peptide sequence derived from this protein was used to
      isolate two very similar cDNA clones encoding novel 500-amino acid proteins, both
      with calculated molecular masses of 55.9 kDa and pIs of 4.87. The data predict
      translation of a preprotein containing a signal peptide of 21 amino acids that is
      removed during maturation. Deglycosylation assays demonstrate that native PFI
      from P. filicina is a glycoprotein. The purified protein is chromophoric with a
      flavin-like UV spectrum and sequence analysis reveals the presence of a flavin
      binding motif near the mature N-terminus. Heterologous expression of active PFI
      in Arabidopsis, using one of the cDNA clones, was successful as evidenced by
      conversion of arachidonic acid to a conjugated triene in an in vitro assay of the
      transgenic plant tissues.

PMID- 12054483
TI  - Functional interactions between the noncovalently associated N- and C-terminal
      halves of mammalian Type I hexokinase.
AB  - The 100 kDa Type I isozyme of mammalian hexokinase has evolved by duplication and
      fusion of a gene encoding an ancestral 50 kDa hexokinase. Although the N- and C
      terminal halves are similar in sequence, they differ in function, catalytic
      activity being associated only with the C-terminal half while the N-terminal half
      serves a regulatory role. The N- and C-terminal halves of rat Type I hexokinase
      have been coexpressed in M + R 42 cells. The halves associate noncovalently to
      produce a 100 kDa form that exhibits characteristics seen with the intact Type I
      isozyme but not with the isolated catalytic C-terminal half, i.e.,
      characteristics that are influenced by interactions between the halves. These
      include a decreased K(m) for the substrate ATP and the ability of P(i) to
      antagonize inhibition by Glc-6-P or its analog, 1-5-anhydroglucitol-6-P. Thus,
      functional interactions between the N- and C-terminal halves do not require their
      covalent linkage.

PMID- 12054484
TI  - Green tea constituent epigallocatechin-3-gallate inhibits angiogenic
      differentiation of human endothelial cells.
AB  - Several independent research studies have shown that consumption of green tea
      reduces the development of cancer in many animal models. Epidemiological
      observations, though inconclusive, are suggesting that green tea consumption may
      also reduce the risk of some cancers in humans. These anti-carcinogenic effects
      of green tea have been attributed to its constituent polyphenols. Angiogenesis is
      a crucial step in the growth and metastasis of cancers. We have investigated the
      effect of the major polyphenolic constituent of green tea, epigallocatechin-3
      gallate (EGCG), on the tube formation of human umbilical vein endothelial cells
      (HUVEC) on matrigel. Tube formation was inhibited by treatment both prior to
      plating and after plating endothelial cells on matrigel. EGCG treatment also was
      found to reduce the migration of endothelial cells in matrigel plug model. The
      role of matrix metalloproteinases (MMP) has been shown to play an important role
      during angiogenesis. Zymography was performed to determine if EGCG had any effect
      on MMPs. Zymographs of EGCG-treated culture supernatants modulated the
      gelatinolytic activities of secreted proteinases indicating that EGCG may be
      exerting its inhibitory effect by regulating proteinases. These findings suggest
      that EGCG acts as an angiogenesis inhibitor by modulating protease activity
      during endothelial morphogenesis.

PMID- 12054485
TI  - Quantitative and qualitative alterations of chondroitin/dermatan sulfates
      accompanied with development of tubulointerstitial nephritis.
AB  - Quantitative and qualitative alterations of renal oversulfated
      chondroitin/dermatan sulfates (C/DSs) accompanied by the development of
      tubulointerstitial nephritis were examined. The rat model with unilateral
      ureteral obstruction (UUO) is a suitable model for study of renal interstitial
      fibrosis, and was utilized in the present study. Cortical regions of serial
      sections of UUO kidney and sham-operated kidney on glass slides were processed
      using a small surgical knife under dark field microscopy. Oversulfated C/DSs in
      tissue sections on a glass slide were degraded to unsaturated disaccharides using
      chondroitinase ABC and ACII digestion in the presence of bacterial collagenase.
      The resulting unsaturated disaccharides were subsequently determined by HPLC.
      These in situ investigations yielded the following results: (1) marked increases
      in oversulfated C/DSs content and decreases in the oversulfation degree of C/DSs
      were observed in fibrous lesions, compared to non-fibrous lesions, and (2)
      iduronic acid content in C/DSs in fibrous lesions was significantly lower than
      that in non-fibrous lesions. These findings indicate that oversulfated C/DSs with
      low-iduronic acid content represent a potential marker for tubulointerstitial
      nephritis.

PMID- 12054486
TI  - Regulation of renal vitamin D receptor is an important determinant of 1alpha,25
      dihydroxyvitamin D(3) levels in vivo.
AB  - The synthesis of 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) is most strongly
      regulated by dietary calcium and the action of parathyroid hormone to increase
      1alpha-hydroxylase (1alpha-OHase) and decrease 24-hydroxylase (24-OHase) in
      kidney proximal tubules. This study examines the hypothesis that 1,25-(OH)(2)D(3)
      synthesis, induced by dietary calcium restriction, is also the result of negative
      feedback regulation blockade. Rats fed a low calcium (0.02%, -Ca) diet and given
      daily oral doses of vitamin D (0, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 microg)
      remained hypocalcemic despite increasing levels of serum calcium in relation to
      the vitamin D dose. Plasma levels of 1,25-(OH)(2)D(3) rose to high levels (1200
      pg/ml) at the high vitamin D dose levels. As expected, thyroparathyroidectomy
      caused a rapid fall in serum 1,25-(OH)(2)D(3). In rats fed a 0.47% calcium diet
      (+Ca) supplemented with vitamin D (4 microg/day), exogenous 1,25-(OH)(2)D(3)
      suppressed renal 1alpha-OHase and stimulated the 24-OHase. In rats fed the -Ca
      diet, vitamin D was unable to suppress the renal 1alpha-OHase or stimulate the
      renal 24-OHase. In contrast, vitamin D was fully able to stimulate intestinal 24
      OHase. Intestinal vitamin D receptor (VDR) was present under all circumstances,
      while kidney VDR was absent under hypocalcemic conditions and present under
      normocalcemic conditions. It appears that tissue-specific down-regulation of VDR
      by hypocalcemia blocks the 1,25-(OH)(2)D(3) suppression of the 1alpha-OHase and
      upregulation of the 24-OHase in the kidney, causing a marked accumulation of 1,25
      (OH)(2)D(3) in the plasma.

PMID- 12054488
TI  - Changes in catalytic activity and association state of pyruvate carboxylase which
      are dependent on enzyme concentration.
AB  - The specific activity of chicken liver pyruvate carboxylase has been shown to
      decrease with decreasing enzyme concentration, even at 100 microM, which is close
      to the estimated physiological concentration. The kinetics of the loss of enzyme
      specific activity following dilution were biphasic. Incubation of dilution
      inactivated enzyme with ATP, acetyl CoA, Mg2+ + ATP or, to a lesser degree, with
      Mg2+ alone resulted in a high degree of reactivation, while no reactivation
      occurred in the presence of pyruvate. The association state of the enzyme before,
      during, and after dilution inactivation has been assessed by gel filtration
      chromatography. These studies indicate that on dilution, there is dissociation of
      the catalytically active tetrameric enzyme species into inactive dimers.
      Reactivation of the enzyme resulted in reassociation of enzymic dimers into
      tetramers. The enzyme was shown to form high molecular weight aggregates at high
      enzyme concentrations.

PMID- 12054487
TI  - Topoisomerase II antagonism and anticancer activity of coordinated derivatives of
      [RuCl(2)(C(6)H(6))(dmso)].
AB  - Topoisomerase II poisoning and anticancer activity by the organometallic compound
      [RuCl(2)(C(6)H(6))(dmso)] was shown by us in an earlier study [Biochemistry 38
      (1999) 4382]. Since high concentrations of this complex were required to achieve
      either effects, we have synthesized four derivatives of this complex in which the
      dimethyl sulphoxide group on the ruthenium atom was replaced with pyridine, 3
      aminopyridine, p-aminobenzoic acid, and aminoguanidine. Three of these molecules
      showed enhanced potency of topoisomerase II poisoning and consequently also
      showed higher anticancer activity in breast and colon carcinoma cells in vitro.
      Detailed analysis of the molecular action of these compounds on topoisomerase II
      activity was carried out using the classical relaxation and cleavage activity of
      the enzyme, which revealed that the compounds poison topoisomerase II by freezing
      the enzyme and enzyme-cleaved DNA in a ternary "cleavage complex". The cleavage
      complex is implicated in the anti-neoplastic activity of these compounds. DNA
      interaction studies showed that these compounds interact with DNA in much the
      same way as [RuCl(2)(C(6)H(6))(dmso)], by external binding of the DNA helix. This
      is unlike most other topoisomerase II poisons, which predominantly interact with
      DNA through intercalation with the double helix.

PMID- 12054489
TI  - Activation and induction of glycine N-methyltransferase by retinoids are tissue-
      and gender-specific.
AB  - Glycine N-methyltransferase (GNMT) is a key protein in the liver that functions
      to regulate S-adenosylmethionine (SAM) and the SAM/S-adenosylhomocysteine ratio.
      Significant GNMT expression is also present in the kidney and pancreas.
      Inappropriate regulation of GNMT may have negative consequences on methyl group
      and folate metabolism. We have demonstrated that retinoid compounds significantly
      elevated hepatic GNMT activity and abundance (approximately 2-fold) in male rats.
      However, pancreatic GNMT activity and abundance were not altered by retinoid
      treatment. Likewise, retinoid administration was without effect on renal GNMT
      activity. Hepatic GNMT activity was also elevated in female rats treated with all
      trans-retinoic acid, but to a lesser extent compared to males. Collectively,
      these results indicate that the modulation of methyl group metabolism by
      retinoids is tissue- and gender-specific, and may compromise the availability of
      methyl groups for SAM-dependent transmethylation reactions. In support of this,
      SAM-dependent synthesis of creatinine was significantly reduced 21% following all
      trans-retinoic acid treatment.

PMID- 12054490
TI  - Implication by site-directed mutagenesis of Arg314 and Tyr316 in the coenzyme
      site of pig mitochondrial NADP-dependent isocitrate dehydrogenase.
AB  - Sequence alignment of pig mitochondrial NADP-dependent isocitrate dehydrogenase
      with eukaryotic (human, rat, and yeast) and Escherichia coli isocitrate
      dehydrogenases reveals that Tyr316 is completely conserved and is equivalent to
      the E. coli Tyr345, which interacts with the 2'-phosphate of NADP in the crystal
      structure [Hurley et al., Biochemistry 30 (1991) 8671-8678]. Lys321 is also
      completely conserved in the five isocitrate dehydrogenases. Either an arginine or
      lysine residue is found among the enzymes from other species at the position
      corresponding to the pig enzyme Arg314. While Arg323 is not conserved among all
      species, its proximity to the coenzyme site makes it a good candidate for
      investigation. The importance of these four amino acids to the function of pig
      mitochondrial NADP-isocitrate dehydrogenase was studied by site-directed
      mutagenesis. Mutants (R314Q, Y316F, Y316L, K321Q, and R323Q) were generated by a
      megaprimer polymerase chain reaction method. Wild-type and mutant enzymes were
      expressed in E. coli and purified to homogeneity. All mutant and wild-type
      enzymes exhibited comparable molecular weights indicative of the dimeric enzyme.
      Mutations do not cause an appreciable change in enzyme secondary structure as
      revealed by circular dichroism measurements. The kinetic parameters (V(max) and
      K(M) values) of K321Q and R323Q are similar to those of wild-type, indicating
      that Lys321 and Arg323 are not involved in enzyme function. R314Q exhibits a 10
      fold increase in K(M) for NADP as compared to that of wild-type, while they have
      comparable V(max) values. These results suggest that Arg314 contributes to the
      affinity between the enzyme and NADP. The hydroxyl group of Tyr316 is not
      required for enzyme function since Y316F exhibits similar kinetic parameters to
      those of wild-type. Y316L shows a 4-fold increase in K(M) for NADP and a decrease
      in V(max) as compared to wild-type, suggesting that the aromatic ring of the Tyr
      of isocitrate dehydrogenase contributes to the affinity for coenzyme, as well as
      to catalysis. The K(i) for NAD of R314Q, Y316F, and Y316L is comparable to that
      of wild-type, indicating that the Arg314 and Tyr316 may be located near the 2'
      phosphate of enzyme-bound NADP.

PMID- 12054491
TI  - Biodegradation of polychlorinated dibenzo-p-dioxins by recombinant yeast
      expressing rat CYP1A subfamily.
AB  - Metabolism of polychlorinated dibenzo-p-dioxins (PCDDs) by recombinant yeast
      cells expressing either rat CYP1A1 or CYP1A2 was examined. When each of the
      dibenzo-p-dioxins (DDs), mono-, di-, and tri-chloroDDs, was added to the cell
      culture of the recombinant yeast, a remarkable metabolism was observed. The
      metabolism contained multiple reactions such as hydroxylation at an unsubstituted
      position, hydroxylation with migration of a chloride substituent, hydroxylation
      with elimination of a chloride substituent, and opening of dioxin ring. The
      distinct difference was observed in substrate specificity and reaction
      specificity between CYP1A1 and CYP1A2. Kinetic analysis using microsomal
      fractions prepared from the recombinant yeast cells revealed that 2,7-dichloroDD
      and 2,3,7-trichloroDD were good substrates for both CYP1A1 and CYP1A2. When 2,3,7
      trichloroDD was added to the yeast cells expressing each of rat CYP1A1 and
      CYP1A2, most of 2,3,7-trichloroDD was first converted to 8-hydroxy-2,3,7
      trichloroDD, and further metabolized to more hydrophilic compounds whose ethereal
      bridges were cleaved. These findings give essential information on the metabolism
      of PCDDs in mammalian liver. In addition, this study indicates the possibility of
      application of microorganisms expressing mammalian cytochrome P450 to
      bioremediation of contaminated soils with dioxins.

PMID- 12054492
TI  - Hsp90 makes the human HBV Pol competent for in vitro priming rather than
      maintaining the human HBV Pol/pregenomic RNA complex.
AB  - Previous studies show that the Hsp90 complex facilitates binding of duck
      hepatitis B virus polymerase on the epsilon stem-loop region in pregenomic RNA
      for the priming of Pol. In this report, we found that Hsp90 also binds to human
      HBV Pol and its binding seems to be involved in in vitro priming of human HBV
      Pol. (i) Inhibition of Hsp90 by anti-Hsp90 antibody (3G3) and (ii) the stripping
      of the Hsp90 by 1 M NaCl buffer containing 1% NP-40 almost completely reduced in
      vitro priming activity of human HBV Pol expressed in insect cells. However,
      binding of human HBV Pol to pregenomic RNA is different from that of duck HBV
      Pol. It seems that Hsp90 makes the human HBV Pol competent for in vitro priming
      rather than maintaining the human HBV Pol/pregenomic RNA complex as duck HBV Pol.
      In addition, although Hsp70 is a component of the Hsp90 complex, Hsp70 can
      directly bind to human HBV Pol without Hsp90.

PMID- 12054493
TI  - Identification of a splice variant of mouse caveolin-2 mRNA encoding an isoform
      lacking the C-terminal domain.
AB  - We identified a splice variant of mouse caveolin-2 mRNA having an intronic
      sequence in place of the third exon (Deltaex3). The entire sequence of full
      length (FL) and Deltaex3 caveolin-2 mRNA was determined; their sizes were 2490
      and 973 bp, respectively. The Deltaex3 mRNA encoded a putative isoform lacking
      the C-terminal 49 amino acids of the authentic caveolin-2. The expression level
      of Deltaex3 was lower than that of FL mRNA, but considerable in some culture
      cells and tissues. The isoform lacking the C-terminus localized to the
      endoplasmic reticulum, while the authentic caveolin-2 was distributed to the
      Golgi and the plasma membrane along with caveolin-1. The result confirmed the
      necessity of the C-terminal domain of caveolin-2 for the caveolar localization,
      and showed the existence of a novel caveolin-2 isoform, which is not recruited to
      caveolae even in the presence of caveolin-1.

PMID- 12054494
TI  - A cluster region of AP-1 responsive elements is required for transcriptional
      activity of mouse ODC gene by hepatocyte growth factor.
AB  - Ornithine decarboxylase (ODC) activity is regulated by a variety of mechanisms
      including transcription, translation, and RNA and protein half-life. Since in
      mouse B16-F1 melanoma cells an early and remarkable (about 6-fold) increase in
      steady state mRNA levels was observed after hepatocyte growth factor (HGF)
      treatment, we investigated the transcriptional regulation of mouse ODC promoter.
      Transient transfection of various ODC-luciferase promoter constructs into the B16
      Fl cells in combination with electrophoretic mobility shift assays identified the
      HGF-responsive element as a cluster of three AP-1 binding sites (-1660 to -1572).
      Even if each site differs from the canonical TPA responsive element for one
      nucleotide, only the first two AP-1 consensus sequences seemed to be functional
      since allowed DNA-binding activity of nuclear proteins after HGF treatment.
      Comparison of the results of transfection assays with the pOD2.5-luc (2.5 kb gene
      fragment) and with the construct deprived of the AP-1 cluster pOD-B-luc showed
      that this 50 bp region was required for ODC transactivating activity in response
      to HGF. Since in B16-F1 cells HGF increased AP-1 activity and the mRNA expression
      of various AP-1 subunits, we may conclude that HGF-induced transcription of mouse
      ODC was largely due to triggering of AP-1 pathway.

PMID- 12054495
TI  - The role of uncoupling proteins in pathophysiological states.
AB  - Until very recently, the uncoupling protein-1 (UCP1), present only in brown
      adipose tissue (BAT), was considered to be the only mitochondrial carrier protein
      that stimulated heat production by dissipating the proton gradient generated
      during respiration across the inner mitochondrial membrane and therefore
      uncoupling respiration from ATP synthesis. Recently, new uncoupling proteins,
      UCP2, UCP3, and UCP4, and brain mitochondrial carrier protein-1 (BMCP-1) have
      been described in mammalian tissues. The present review deals with the possible
      role of these proteins in different pathological conditions involving alterations
      in energy balance such as obesity or cachexia. In conclusion, the emergence of
      the UCP family has altered the approaches to bioenergetics and stressed the
      importance of uncoupling respiration in different pathophysiological conditions.
      An extensive qualitative and quantitative characterization of the new members of
      the UCP family in mammalian tissues will allow a better understanding of the
      molecular and regulatory mechanisms of thermogenesis and energy metabolism. At
      this point, we hope that the knowledge presented in the present review will not
      only stimulate a debate about the role of the UCP family in disease but also lead
      to applications beneficial for human health.

PMID- 12054496
TI  - Viral fusion peptides and identification of membrane-interacting segments.
AB  - Viral envelope glycoproteins promote infection by mediating fusion between viral
      and cellular membranes. Fusion occurs after dramatic conformational changes
      within fusion proteins, leading to the exposure of a short stretch of mostly
      apolar residues, termed the fusion peptide, which is presumed to insert into the
      membrane and initiate the fusion process. The typical global composition of
      fusion peptides, rich in hydrophobic but also in small amino acids such as
      alanine and glycine, was used here as bait to detect other peptidic segments that
      can insert into membranes. We so evidenced a similar composition in several
      cytotoxic peptides, which promote pore formation such as peptides involved in
      amyloidoses and hydrophobic alpha-hairpins of pore-forming toxins. It is
      suggested that the structural plasticity observed for several membrane active
      peptides can be conferred by this particular global amino acid composition, which
      could be thus used to predict such functional behavior from genome data.

PMID- 12054497
TI  - Identification of novel putative membrane proteins selectively expressed during
      adipose conversion of 3T3-L1 cells.
AB  - Fat tissue plays a critical role in the regulation of energy metabolism. Here we
      report the proteomic identification of a novel _fa_t tissue-specific _l_ow
      molecular weight _p_rotein (Falp) which responds to insulin. Falp is
      preferentially expressed in adipocytes but not in preadipocytes, as shown by two
      dimensional gel electrophoresis. Northern blot analysis shows that the Falp gene
      is predominantly expressed in brown and white fat tissues, but not in any other
      tissues examined. Human homologs of mouse Falp are found to exist as two
      alternatively spliced isoforms, which share the same N-terminus but have
      different C-termini. Both human and mouse Falp contain a conserved putative
      transmembrane domain. Immunofluorescent analyses of 3T3-L1 adipocytes show that
      Falp protein strictly localizes at a compact perinuclear membrane compartment.
      Treatment of cells with insulin induces the redistribution of Falp into numerous
      discrete spotty structures spreading throughout the cytoplasm. Whereas the
      function of Falp is currently unclear, its tissue specific expression and the
      responsiveness to insulin suggest that Falp might be involved in a process
      specifically restricted to adipose tissue function, such as vesicular transport
      and protein secretion.

PMID- 12054498
TI  - Extracellular acidification parallels insulin secretion in INS-1 and HIT-T15 beta
      cell lines.
AB  - As an alternative to manual assays that track insulin secretion, we tested a
      silicon-based biosensor that allows automated monitoring of extracellular
      acidification. Glucose stimulation of INS-1 and HIT-T15 cells resulted in a rapid
      increase in extracellular acidification in a biphasic and concentration-dependent
      fashion much like insulin secretion (EC(50) INS-1=5 mM and HIT-T15=1 mM). This
      response was attenuated by verapamil (10 microM) and stimulated by administration
      of glybenclamide (100 nM) or KCl-induced (40 mM) depolarization. These
      experiments suggest that automated monitoring of extracellular pH may be a useful
      assay and support the relevance of linking metabolic activity to insulin
      secretion.

PMID- 12054500
TI  - Formation of MUC1 metabolic complex is conserved in tumor-derived and normal
      epithelial cells.
AB  - MUC1 is abundantly expressed at the surface of epithelial cells in many tissues
      and their carcinomas. In humans, genetic polymorphism and differential splicing
      produce isoforms that may contribute to MUC1 participation in protection of the
      cell surface, modulation of cell-cell interactions, signaling, and metastasis.
      Biosynthetic and processing studies in tumor-derived cell lines indicate that
      cell surface MUC1 consists of a non-covalently associated heterodimer of separate
      cytoplasmic tail and extracellular domains. This heterodimer results from a
      single precursor proteolytically cleaved intracellularly. To determine whether
      similar processing of this isoform occurs in normal epithelial cells, we have
      examined cell-associated MUC1 and MUC1 released into medium by normal human
      uterine, mammary, and prostate epithelial cells. Cell-associated MUC1/REP was
      extracted as an SDS labile complex which was resistant to dissociation by
      boiling, urea, sulfhydryl reduction, peroxide, high salt, or low pH and was
      present in all normal cells examined. Addition of various proteolytic inhibitors
      during extraction had no effect on the proportion of this complex detected. MUC1
      released into the medium was not associated with a particulate fraction (100,000g
      insoluble) and lacked the cytoplasmic tail. MUC1/REP and the MUC1 isoform lacking
      the transmembrane/cytoplasmic tail region, MUC1/SEC, mRNA were detected in all
      normal cells examined indicating that both shed and secreted MUC1 are likely to
      contribute to soluble forms found in culture media.

PMID- 12054499
TI  - FGF-2 and TPA induce matrix metalloproteinase-9 secretion in MCF-7 cells through
      PKC activation of the Ras/ERK pathway.
AB  - Matrix metalloproteinases (MMPs) play an important role in cancer metastasis.
      Here, we investigated the effect of fibroblast growth factor-2 (FGF-2) and 12-O
      tetradecanoylphorbol-13-acetate (TPA) on the secretion of type IV collagenases
      (MMP-2, MMP-9) in breast cancer MCF-7 cells. As shown by gelatin zymography, both
      FGF-2 and TPA stimulated the secretion of MMP-9 in MCF-7 cells while they did not
      change the level of MMP-2 secretion. Signaling cascade studies indicated that
      both FGF-2 and TPA induced Ras activation, c-Raf phosphorylation, mitogen
      activated protein kinase/ERK kinase (MEK(1/2)) phosphorylation, and extracellular
      signal-regulated kinase (ERK(1/2)) phosphorylation. The FGF-2- and TPA-induced
      MMP-9 secretion was significantly inhibited by transient transfection of MCF-7
      cells with dominant negative Ras (Ras-N17) and by treatment with MEK(1/2)
      inhibitor PD98059. A pan-protein kinase C (PKC) inhibitor, GF109203X, was found
      to totally abolish the FGF-2- and TPA-induced MMP-9 secretion and ERK(1/2)
      phosphorylation. Use of isoform-specific PKC inhibitors such as Rotllerin and
      Go6976 suggested, moreover, that the PKC-delta isoform is a likely component of
      FGF-2 and TPA trophic signaling. These results demonstrated that FGF-2 and TPA
      induce MMP-9 secretion in MCF-7 cells mainly through PKC-dependent activation of
      the Ras/ERK(1/2) signaling pathway.

PMID- 12054501
TI  - Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) phosphorylates
      glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 through direct
      interaction.
AB  - Serum and glucocorticoid-inducible kinase-like kinase (SGKL) has been identified
      as a new integrator that decodes lipid signals produced by the activation of
      phosphoinositide 3-kinase (PI3K). SGKL is activated via its lipid-binding domain
      (phox homology domain) in response to PI3K signaling. However, downstream targets
      of SGKL as well as the role of SGKL as a mediator in PI3K signaling in human
      tissues remain to be established. In this study, we identified human glycogen
      synthase kinase 3 beta (GSK-3beta) as a specific interacting partner with SGKL in
      a yeast two-hybrid screening of human brain cDNA library. The association between
      these two proteins is confirmed independently in human embryonic kidney (HEK293)
      cells by co-immunoprecipitation. Furthermore, the kinase activity of wild-type
      SGKL was required for the in vitro phosphorylation of a GSK-3 crosstide fusion
      protein at serine-21/9 as demonstrated with a Phospho-GSK-3alpha/beta (Ser21/9)
      specific antibody. The present results provide strong evidences that SGKL could
      utilize GSK-3beta as a direct downstream target by phosphorylating GSK-3beta at
      serine-9.

PMID- 12054503
TI  - Eliminating membrane depolarization caused by the Alzheimer peptide Abeta(1-42,
      aggr.).
AB  - A high-throughput screen found compounds that eliminate the dramatic membrane
      depolarization caused by the aggregated Alzheimer Abeta1-42 peptide, which
      activates mGluR1 receptors. The library was composed of known biologically active
      compounds; the cell-based assay measured the changes of membrane potential with a
      slow-acting voltage-sensitive dye. We found 10 potentially useful compounds, some
      of which reduce the Abeta-induced membrane depolarization up to 96%.
      Interestingly, the active compounds include specific tyrosine kinase inhibitors
      and inhibitors of certain chloride channels. We deduce that mGluR1 receptors,
      activated by Abeta1-42 or otherwise, can control the membrane potential via
      downstream activation of certain tyrosine kinases and certain ion channels.
      Dopaminergic and serotonergic agonists that emerged from the screen presumably
      compensate for the Abeta-induced membrane depolarization by themselves causing a
      hyperpolarization. The hit compounds, whose pharmacokinetics are known, show
      promise for the restoration of cognitive function in the treatment of early and
      mid-stage Alzheimer's disease.

PMID- 12054502
TI  - Mechanism of membrane depolarization caused by the Alzheimer Abeta1-42 peptide.
AB  - We report a novel observation that the neurotoxic Alzheimer peptide Abeta1-42,
      when pre-incubated, causes a dramatic and lasting membrane depolarization in
      differentiated human hNT neuronal cells and in rodent PC12 cells in a
      concentration-dependent manner. This phenomenon involves activation of the
      metabotropic glutamate receptor, mGluR(1). Abeta-induced membrane depolarization
      in PC12 cells is sensitive to mGluR(1) antagonists and to pertussis and cholera
      toxins, indicating the involvement of particular G-proteins. The effect is
      different from the known ability of aggregated Abeta1-42 to cause a calcium
      influx. Since mGluR(1) agonists mimic the Abeta effect, we deduce that in this
      cell system glutamate can control the membrane potential and thereby the
      excitability of its target neurons. We propose that Abeta-induced membrane
      depolarization described here leads in Alzheimer's disease to hyperexcitability
      of affected neurons and is a crucially important molecular mechanism for beta
      amyloid toxicity and cognitive dysfunction in the disease.

PMID- 12054504
TI  - Plant pre-mRNA splicing in fission yeast, Schizosaccharomyces pombe.
AB  - Pre-mRNA splicing or the removal of introns from precursor messenger RNAs depends
      on the accurate recognition of intron sequences by the splicing machinery. We
      have analyzed various aspects of intron sequence and structure in relation to
      splice site selection and splicing efficiency of a plant gene AmA1 in
      Schizosaccharomyces pombe. Earlier, we reported the cloning of AmA1, a seed
      albumin gene from Amaranthus hypochondriacus [A. Raina, A. Datta, Proc. Natl.
      Acad. Sci. USA 89 (1992) 11774]. In the absence of an in vitro splicing system
      for plants, the expression of AmA1 genomic clone in S. pombe has been used to
      analyze splicing of intron constructs. We aim to focus on S. pombe as a possible
      alternative and examined its effectiveness as a host for plant gene splicing. The
      results show here that pre-mRNA transcripts of AmA1 gene underwent splicing in S.
      pombe.

PMID- 12054505
TI  - Gene regulation by human orthologs of Drosophila heterochromatin protein 1.
AB  - Heterochromatin protein 1 (HP1) functions in gene silencing, transcriptional
      regulation, and chromatin remodeling. Drosophila HP1 enhances position effect
      variegation and has also been shown to repress transcription of some euchromatic
      genes and activate some heterochromatic ones. The purpose of this study was to
      determine if human orthologs of Drosophila HP1 differentially regulate
      transcription by identifying genes that are targets for regulation by HP1 family
      proteins in human cells. Using a gene expression array, we identify several genes
      regulated by overexpression of the three human HP1 family proteins HP1(Hsalpha),
      HP1(Hsbeta), and HP1(Hsgamma). We show further that overexpressed HP1(Hsalpha)
      and HP1(Hsbeta) repress the transcription of four human genes while overexpressed
      HP1(Hsgamma) enhances transcription of the same genes. These results show that
      different human HP1 family proteins can potentially repress or activate the same
      genes.

PMID- 12054506
TI  - The motilin pharmacophore in CHO cells expressing the human motilin receptor.
AB  - We performed a structure-activity study with the human motilin receptor, which
      was recently cloned from thyroid tissue. N-terminal fragments, Ala-analogs of
      motilin, and motilides were tested in a cell line that expresses the cloned human
      motilin receptor and apoaequorin. Full potency to induce calcium fluxes was
      obtained with N-terminal fragments of 14 amino acids. Motilin fragments 1-14 in
      which residues 1 (Phe), 4 (Ile), and 7 (Tyr) were replaced by Ala showed the
      largest reduction in potency. Only motilides with an enol configuration had
      markedly higher potencies compared to erythromycin A. The potencies to induce
      Ca(2+) fluxes correlated strongly with rabbit binding and contractility data,
      suggesting that the cloned receptor is indeed the motilin receptor, responsible
      for contractile effects. Conservation of the motilin pharmacophore in evolution
      indicates an important physiological role of motilin.

PMID- 12054507
TI  - BACE1 interacts with nicastrin.
AB  - Beta-amyloid peptide (Abeta) is generated through the proteolytic cleavage of
      beta-amyloid precursor protein (APP) by beta- and gamma-secretases. The beta
      secretase, BACE1, initiates Abeta formation followed by gamma-cleavage within the
      APP transmembrane domain. Although BACE1 localizes in the transGolgi network
      (TGN), its physiological substrates and modulators are not known. In addition,
      the relationship to other secretase(s) also remains unidentified. Here, we
      demonstrate that BACE1 binds to nicastrin, a component of gamma-secretase
      complexes, in vitro, and that nicastrin activates beta-secretase activity in COS
      7 cells.

PMID- 12054508
TI  - Mutagenesis and peptide analysis of the DRY motif in the alpha2A adrenergic
      receptor: evidence for alternate mechanisms in G protein-coupled receptors.
AB  - In G protein-coupled receptors (GPCRs), a conserved aspartic acid in the DRY
      motif at the cytoplasmic end of helix 3 regulates the transition to the active
      state, while the adjacent arginine is crucial for G protein activation. To
      examine the functions of these two residues, we made D130I and R131Q mutations in
      the alpha2A adrenergic receptor (AR). We demonstrate that, unlike other GPCRs,
      the alpha2A AR is not constitutively activated by the D130I mutation, although
      the mutation increases agonist affinity. While the R131Q mutation severely
      disrupts function, it decreases rather than increasing agonist affinity as seen
      in other GPCRs. We then investigated the molecular effects of the same mutations
      in a peptide model and showed that Arg131 is not required for peptide-mediated G
      protein activation. These results indicate that the alpha2A AR does not follow
      the conventional GPCR mechanistic paradigm with respect to the function of the
      DRY motif.

PMID- 12054509
TI  - Identification of nuclear import and export signals within the structure of the
      zinc finger protein TIS11.
AB  - TIS11, a member of the CCCH zinc finger protein family, functions as a positive
      transcriptional regulator. TIS11 was localized in both the cytoplasm and nucleus
      when transiently expressed in COS-7 cells. Upon treatment with leptomycin B, a
      specific inhibitor of the nuclear export receptor CRM1, a marked nuclear
      accumulation of TIS11 was observed, indicating that TIS11 shuttles between the
      nucleus and the cytoplasm. By deletion studies using a green fluorescent protein
      fusion system, we have mapped a functional nuclear localization signal (NLS) to a
      region containing two tandem repeats of the zinc finger motif of TIS11. A site
      directed mutagenesis analysis of TIS11 NLS has revealed the critical importance
      of two arginine residues (Arg127 and Arg131 in the rat TIS11). Furthermore, we
      demonstrated that the N-terminal Leu-rich region of TIS11 serves as an LMB
      sensitive nuclear export signal (NES), indicating that TIS11 follows a CRM1
      mediated export pathway. These results suggest that TIS11 is subject to constant
      nucleocytoplasmic shuttling due to its NLS and NES.

PMID- 12054510
TI  - H(2)O(2)-induced AP-1 activation and its effect on p21(WAF1/CIP1)-mediated G2/M
      arrest in a p53-deficient human lung cancer cell.
AB  - Cellular response to oxidative stress is a complex process that is often
      connected to cell cycle regulation. The present study examines the effect of
      H(2)O(2) on cell cycle regulation and involvement of reactive oxygen species
      (ROS) in these H(2)O(2)-induced responses in a p53-deficient human lung carcinoma
      cell line, H1299. Treatment of the cells with H(2)O(2) caused a G2/M phase
      arrest. Among the redox-sensitive transcription factors, NF-kappaB and AP-1, we
      found that only AP-1 was activated by 200 microM H(2)O(2) in human lung cells.
      Furthermore, electrophoretic mobility shift assays revealed that H(2)O(2)
      enhanced the DNA binding of AP-1 to a putative AP-1 binding element (TGAGGAA) in
      the p21(WAF1/CIP1) promoter region (between -2203 and -2197 nucleotides upstream
      of the transcription initiation site). An increase in c-Jun phosphorylation by
      ERK was also found to accompany the increased AP-1 activity as detected by
      Western blot. PD98059, a specific inhibitor of MEK, diminished H(2)O(2)-induced
      phosphorylation of c-Jun and DNA binding activity of AP-1, decreased expression
      of p21(WAF1/CIP1), and released the cells from G2/M arrest. Taken together, these
      results revealed a novel AP-1 binding site in the promoter region of
      p21(WAF1/CIP1) and a possible cell cycle regulation mechanism mediated by
      activation of a redox-dependent ERK signaling pathway.

PMID- 12054511
TI  - Analysis of gene expression patterns during glucocorticoid-induced apoptosis
      using oligonucleotide arrays.
AB  - To determine the genes responsible for mediating the effects of glucocorticoids
      (GCs) on leukemic cells, transcriptional changes in GC-sensitive human pre-B
      leukemia 697 cells during GC-induced apoptosis were monitored using
      oligonucleotide microarrays. To circumvent the challenge of recovering mRNAs from
      dying cells, we compared the pattern of gene expression with that of 697 cells
      protected from apoptosis by transfection with bcl-2. Of the 12,000 genes examined
      for their response to GC, 93 genes were induced and 28 genes were repressed, many
      of which are known to be implicated in signal transduction, growth arrest, and
      transcription. These included the signal transduction-related genes encoding
      SOCS1, SOCS2, FKBP51, DSCR1, p56lck, and four protein kinase phosphatases. Growth
      arrest-related genes encoding p19(INK4d) and several Myc inhibitors were induced
      in response to the GC treatment. Anti-proliferative- or apoptosis-related genes
      encoding BTG1, BTG2, and granzyme A were also found to be transcriptionally up
      regulated by GC. In addition, the regulation of genes encoding the glucocorticoid
      receptor and steroid receptor coactivator-1 suggested autoregulation of a GC
      mediated signaling pathway.

PMID- 12054512
TI  - Immunohistochemical colocalization of Yellow and male-specific Fruitless in
      Drosophila melanogaster neuroblasts.
AB  - The Drosophila melanogaster fruitless gene encodes multiple male-specific
      transcription factors that are hypothesized to regulate a hierarchy of genes
      responsible for the development of male courtship behavior. Here we show that
      there are dramatically increased levels of the protein product of the male
      courtship behavior gene yellow associated with male-specific Fruitless protein in
      a subset of neuroblasts in third-instar larval male brains. We hypothesize that
      yellow is downstream of fruitless in a male courtship behavior developmental
      genetic pathway.

PMID- 12054513
TI  - Micro-dystrophin cDNA ameliorates dystrophic phenotypes when introduced into mdx
      mice as a transgene.
AB  - The adeno-associated virus vector is a good tool for gene transfer into skeletal
      muscle, but the length of a gene that can be incorporated is limited. To develop
      a gene therapy for Duchenne muscular dystrophy, we generated a series of rod
      truncated micro-dystrophin cDNAs: M3 (one rod repeat, 3.9 kb), AX11 (three rod
      repeats, 4.4 kb), and CS1 (four rod repeats, 4.9 kb). These micro-dystrophins,
      driven by a CAG promoter, were used to produce transgenic (Tg) mdx mice and all
      three micro-dystrophins were shown to localize at the sarcolemma together with
      the expression of dystrophin-associated proteins. Among them, CS1 greatly
      improved dystrophic phenotypes of mdx mice and contractile force of the diaphragm
      in particular was restored to the level of normal C57BL/10 mice. AX11 modestly
      ameliorated the dystrophic pathology, but, importantly, M3-Tg mdx mice still
      showed severe dystrophic phenotypes. These data suggest that the rod structure,
      and its length in particular, is crucial for the function of micro-dystrophin.

PMID- 12054514
TI  - A new multidrug resistance protein at the blood-brain barrier.
AB  - Porcine brain capillary endothelial cells (PBCEC) cultured in serum-free and
      hydrocortisone supplemented medium are characterised by high transendothelial
      electrical resistances and low cell monolayer permeabilities for small solutes
      very similar to the blood-brain barrier (BBB) in vivo. Differential screening of
      a subtracted cDNA library disclosed a 2.1-kb mRNA that is overexpressed in
      hydrocortisone treated PBCEC relative to untreated cells. The mRNA encodes a 656
      aa member of the ATP-binding cassette (ABC) superfamily of transporters that we
      named brain multidrug resistance protein (BMDP). Phylogenetic analysis and
      multiple sequence alignment showed that porcine BMDP is most related to the human
      and mouse breast cancer resistance protein (BCRP). Northern blot analysis
      revealed that BMDP is expressed in brain tissue in vivo and was predominantly
      localised within the endothelial cells isolated from brain capillaries. Thus, we
      identified a new transport protein at the BBB that might play an important role
      in the exclusion of xenobiotics from the brain.

PMID- 12054515
TI  - The effect of TGF-beta receptor binding peptides on smooth muscle cells.
AB  - TGF-beta1 is a potent regulator of vascular smooth muscle cell (VSMC)
      proliferation, migration, and extracellular matrix (ECM) synthesis. In this
      study, we selected two peptides, IM-1 and IM-2, that bind to the TGF-beta type II
      receptor (TGF-beta RII) using phage display. IM-1 and IM-2 bind to the TGF-beta
      RII, with a K(d) of 1 microM. Like TGF-beta, IM-1 induced VSMC chemotaxis and PAI
      1 mRNA expression, as determined using Boyden chambers and real time quantitative
      PCR. In contrast, IM-2 had no effect on VSMC chemotaxis or PAI-1 induction.
      Induction of ECM synthesis, involving proteins such as osteopontin and alpha
      smooth muscle actin, was determined by ELISA. Osteopontin expression was
      inhibited by both peptides, but TGF-beta-induced alpha-smooth muscle actin
      expression could only be inhibited by IM-1. In conclusion, IM-1 activity on VSMC
      is agonistic with TGF-beta, except for ECM synthesis, whereas the IM-2 peptide is
      antagonistic for some examined TGF-beta functions.

PMID- 12054516
TI  - Identification of genes responsive to sodium butyrate in colonic epithelial
      cells.
AB  - We identified genes responsive to sodium butyrate (SB) in colonic epithelial
      cells using cDNA microarrays. Treatment with 2 mM SB of colonic epithelial cells
      (MCE301), which was derived from transgenic mice harboring a temperature
      sensitive simian virus 40 large T-antigen, arrested cell growth and showed a
      differentiated phenotype accompanying an increase in alkaline phosphatase
      activity. Of the approximately 900 genes analyzed, SB down-regulated 25 genes and
      up-regulated 88 genes by a factor of 2.0 or greater. Northern blot or TaqMan and
      Western blot analyses confirmed that the mRNA and protein levels of cyclin D1 and
      the level of proliferating cell nuclear antigen decreased, whereas the levels of
      integrin beta1 and osteopontin increased. The present results regarding the
      changes in gene expression, arrived at using microarrays, will provide a basis
      for a further understanding of the molecular mechanisms of cell growth arrest and
      differentiation in response to SB in colonic epithelial cells.

PMID- 12054517
TI  - Characterization of CeHDA-7, a class II histone deacetylase interacting with MEF
      2 in Caenorhabditis elegans.
AB  - As a result of screen searching for proteins interacting with MEF-2 transcription
      factor, we have identified the hda-7 gene in Caenorhabditis elegans. The hda-7
      locus encodes a class II histone deacetylase containing a highly conserved
      catalytic domain. C. elegans HDA-7 protein translated in vitro demonstrated a
      direct interaction with CeMEF-2, as shown in other organisms. CeHDA-7 is
      abundantly expressed in body-wall muscle cells, neurons, and hypodermal seam
      cells, similar to CeMEF-2 expression patterns. Consistent with previously known
      phenotypes observed in mef-2 deletion mutants [Dev. Biol. 223 (2000) 431], RNA
      interference targeted for hda-7 did not result in muscle function or
      developmental defects.

PMID- 12054518
TI  - Pseudorabies virus DNA-binding protein stimulates the exonuclease activity and
      regulates the processivity of pseudorabies virus DNase.
AB  - The pseudorabies virus (PRV) DNase is an alkaline exonuclease and endonuclease,
      which exhibits an Escherichia coli RecBCD-like catalytic function. The PRV DNA
      binding protein (DBP) promotes the renaturation of complementary single strands
      of DNA, which is an essential function for recombinase. To investigate the
      functional and physical interactions between PRV DBP and DNase, these proteins
      were purified to homogeneity. PRV DBP stimulated the DNase activity, especially
      the exonuclease activity, in a dose-dependent fashion. Acetylation of DBP by
      acetic anhydride resulted in a loss of DNA-binding ability and a 60% inhibition
      of the DNase activity, suggesting that DNA-binding ability of PRV DBP was
      required for stimulating the DNase activity. PRV DNase behaved in a processive
      mode; however, it was converted into a distributive mode in the presence of DBP,
      implying that PRV DBP stimulated the dissociation of DNase from DNA substrates.
      The physical interaction between DBP and DNase was further analyzed by enzyme
      linked immunosorbent assay, and a significant interaction was observed. Thus,
      these results suggested that PRV DBP interacted with PRV DNase and regulated the
      DNase activity in vitro.

PMID- 12054519
TI  - The fatty acid translocase (FAT)/CD36 and the glucose transporter GLUT4 are
      localized in different cellular compartments in rat cardiac muscle.
AB  - The fatty acid translocase (FAT)/CD36 plays an important role in the acute
      regulation of fatty acid uptake in muscle tissue. We studied the subcellular
      distribution of FAT/CD36 in rat cardiac muscle after in vivo insulin stimulation
      by membrane fractionation and immunoisolation of GLUT4- and FAT/CD36-vesicles.
      FAT/CD36 was equally present in both plasma and microsomal membranes with no
      effect of insulin on the cellular distribution, whereas GLUT4 increased 2- to 3
      fold in the plasma membrane. FAT/CD36 resides in one intracellular pool, whereas
      GLUT4 is present in two distinct pools. Immunoadsorption of GLUT4-vesicles
      indicated that FAT/CD36 is undetectable in these vesicles. Likewise, no GLUT4
      could be detected in FAT/CD36-vesicles. These vesicles contain a high amount of
      Rab11 that remained unaffected after insulin stimulation, whereas Rab11 increased
      about 3-fold in the GLUT4-vesicles in response to insulin. These data show that
      GLUT4 and FAT/CD36 do not co-localize in cardiac muscle and that FAT/CD36 is not
      redistributed in response to insulin in the heart. Rab11 may be involved in
      endosomal recycling of FAT/CD36, however, insulin-associated Rab11 functions
      appear to be limited to GLUT4-vesicles.

PMID- 12054520
TI  - Nestin-positive progenitor cells derived from adult human pancreatic islets of
      Langerhans contain side population (SP) cells defined by expression of the ABCG2
      (BCRP1) ATP-binding cassette transporter.
AB  - The disease diabetes mellitus arises as a consequence of a failure of the beta
      cells in the islets of Langerhans of the pancreas to produce insulin in the
      amounts required to meet the needs of the body. Whole pancreas or islet
      transplants in patients with severe diabetes effectively restore insulin
      production. A lack of availability of donor pancreata requires the development of
      alternative sources of islets such as the ex vivo culture and differentiation of
      stem/progenitor cells. Earlier we discovered multipotential progenitor cells in
      islets isolated from adult human pancreata that express the neural stem cell
      marker nestin: nestin-positive islet-derived progenitor cells (NIPs). Recently it
      was shown that the exclusion of the Hoechst 33342 dye, which defines the
      pluripotential side population (SP) of hematopoietic stem cells, is mediated by
      the ATP-binding cassette transporter, ABCG2. Here we report that the human islet
      derived NIPs contain a substantial subpopulation of SP cells that co-express
      ABCG2, MDR1, and nestin. Thus NIPs may be a potential source of adult
      pluripotential stem/progenitor cells useful for the production of islet tissue
      for transplantation into diabetic subjects.

PMID- 12054521
TI  - Expression and functional analysis of an inhibitor of apoptosis protein from
      Trichoplusia ni.
AB  - An inhibitor of the apoptosis protein (IAP) family gene from Trichoplusia ni, Tn
      IAP1v, a variant of lepidopteran Tn-IAP1, was cloned by RT-PCR. There are six
      single nucleotide polymorphisms between the two Tn-IAP1 variants, resulting in
      three predicted single amino acid polymorphisms. With the GST fusion expression
      system, soluble recombinant Tn-IAP1v was highly expressed in Escherichia coli and
      then purified by affinity chromatography. Caspase inhibition assays indicated
      that recombinant Tn-IAP1v could specifically inhibit human caspase-9 in vitro
      instead of caspase-3, -7, and -8, which was further confirmed by the observation
      that recombinant Tn-IAP1v can directly bind caspase-9 in the protein pull-down
      assay. These results suggested that Tn-IAP1v might serve as an initiator caspase
      inhibitor in vivo in the conserved mitochondria apoptotic pathway.

PMID- 12054522
TI  - Inhibitory effect of bFGF on endochondral heterotopic ossification.
AB  - Basic fibroblast growth factor (bFGF) is reported to stimulate repair of fracture
      and bony defects in in vivo animal studies. However, most studies performed in
      vitro demonstrate inhibitory effect of bFGF on cartilage and bone
      differentiation. To understand the discrepancy observed in in vivo and in vitro
      studies, we evaluated the effect of bFGF on chondro-osteogenesis initiated by
      bone matrix powder (MP). MP was implanted in the murine hamstring muscles with or
      without administration of bFGF. Injection of 1 microg of bFGF markedly reduced
      the size of heterotopic bone induced by MP, as detected by X-ray. Injection of 10
      microg of bFGF completely inhibited ossification and only fibrous tissues were
      observed at the site of MP implantation. The expressions of alkaline phosphatase
      and osteocalcin mRNAs, markers for bone differentiation, were completely
      suppressed by 10 microg of bFGF. These results demonstrate the inhibitory effect
      of bFGF on endochondral ossification in vivo, implicating a precaution for its
      use in musculo-skeletal disorders.

PMID- 12054523
TI  - Inositol(1,4,5)trisphosphate signal triggers a receptor-mediated ATP release.
AB  - Intracellular signal transduction pathways involved in ATP release evoked by
      angiotensin II (Ang II) were investigated in cultured guinea pig Taenia coli
      smooth muscle cells. Ang II (0.3-1 microM) elicited substantial release of ATP
      from the cells, but not from a human fibroblast cell line. However, Ang II even
      at 10 microM failed to cause a leakage of lactate dehydrogenase (LDH) from the
      smooth muscle cells. The release of ATP by Ang II was suppressed by 10 microM
      SC52458, an AT1 receptor antagonist, not by 10 microM PD123319, an AT2 receptor
      antagonist. The evoked release of ATP was almost completely inhibited in the
      presence of 10 microM U73122, a phospholipase C inhibitor, and 0.5 microM
      thapsigargin, a Ca2+-ATPase inhibitor. Furthermore, the release was hampered by
      50 microM BAPTA/AM, an intracellular Ca2+ chelator, but not by 0.1 microM
      nifedipine, a voltage gated Ca2+ channel inhibitor. The basal release of ATP was
      increased by BAPTA/AM, but was reduced by U-73122. Ang II enhanced
      instantaneously inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) accumulation in the
      cells. The enhancing effect was perfectly antagonized by SC52458. These findings
      suggest that intracellular Ca2+ signals activated via stimulation of Ins(1,4,5)P3
      receptor are involved in the release of ATP evoked by Ang II.

PMID- 12054524
TI  - Lectin as a marker for staining and purification of embryonic pancreatic
      epithelium.
AB  - The embryonic pancreatic epithelium, and later the ductal epithelium, is known to
      give rise to the endocrine and exocrine cells of the developing pancreas, but no
      specific surface marker for these cells has been identified. Here, we utilized
      Dolichos Biflorus Agglutinin (DBA) as a specific marker of these epithelial cells
      in developing mouse pancreas. From the results of an immunofluorescence study
      using fluorescein-DBA and pancreatic specific cell markers, we found that DBA
      detects specifically epithelial, but neither differentiating endocrine cells nor
      acinar cells. We further applied this marker in an immunomagnetic separation
      system (Dynabead system) to purify these putative multi-potential cells from a
      mixed developing pancreatic cell population. This procedure could be applied to
      study differentiation and cell lineage selections in the developing pancreas, and
      also may be applicable to selecting pancreatic precursor cells for potential
      cellular engineering.

PMID- 12054525
TI  - Caenorhabditis elegans reticulon interacts with RME-1 during embryogenesis.
AB  - Reticulon (RTN) family proteins are localized in the endoplasmic reticulum (ER).
      At least four different RTN genes have been identified in mammals, but in most
      cases, the functions of the encoded proteins except mammalian RTN4-A and RTN4-B
      are unknown. Each RTN gene produces 1-3 proteins by different promoters and
      alternative splicing. In Caenorhabditis elegans, there is a single gene (rtn
      gene) encoding three reticulon proteins, nRTN-A, B, and C. mRNA of nRTN-C is
      expressed in germ cells and embryos. However, nRTN-C protein is only expressed
      during embryogenesis and rapidly disappears after hatch. By yeast two-hybrid
      screening, two clones encoding the same C-terminal region of RME-1, a protein
      functioning in the endocytic recycling, were isolated. These findings suggest
      that nRTN-C functions in the endocytic pathway during embryogenesis.

PMID- 12054526
TI  - Aspirin potently inhibits oxidative DNA strand breaks: implications for cancer
      chemoprevention.
AB  - Epidemiological studies have suggested that the use of aspirin is associated with
      a decreased incidence of human malignancies, particularly colorectal cancer.
      Since reactive oxygen species (ROS) are critically involved in multistage
      carcinogenesis, this study was undertaken to examine the ability of aspirin to
      inhibit ROS-mediated DNA damage. Hydrogen peroxide (H2O2)+Cu(II) and hydroquinone
      (HQ) + Cu(II) were used to cause oxidative DNA strand breaks in phiX-174 plasmid
      DNA. We demonstrated that the presence of aspirin at concentrations (0.5-2 mM)
      compatible with amounts in plasma during chronic anti-inflammatory therapy
      resulted in a marked inhibition of oxidative DNA damage induced by either
      H2O2/Cu(II) or HQ/Cu(II). The inhibition of oxidative DNA damage by aspirin was
      exhibited in a concentration-dependent manner. Moreover, aspirin was found to be
      much more potent than the hydroxyl radical scavengers, mannitol and dimethyl
      sulfoxide, in protecting against the H2O2/Cu(II)-mediated DNA strand breaks.
      Since the reduction of Cu(II) to Cu(I) is crucially involved in both H2O2/Cu(II)-
      and HQ/Cu(II)-mediated formation of hydroxyl radical or its equivalent, and the
      subsequent oxidative DNA damage, we examined whether aspirin could inhibit this
      Cu(II)/Cu(I) redox cycle. It was observed that aspirin at concentrations that
      showed the inhibitory effect on oxidative DNA damage did not alter the
      Cu(II)/Cu(I) redox cycle in either H2O2/Cu(II) or HQ/Cu(II) system. In addition,
      aspirin was not found to significantly scavenge H2O2. This study demonstrates for
      the first time that aspirin potently inhibits both H2O2/Cu(II)- and HQ/Cu(II)
      mediated oxidative DNA strand breaks most likely through scavenging the hydroxyl
      radical or its equivalent derived from these two systems. The potent inhibition
      of oxidative DNA damage by aspirin may thus partially contribute to its
      anticancer activities observed in humans.

PMID- 12054527
TI  - VEGF and VEGF receptor levels in retinal and brain-derived endothelial cells.
AB  - Vascular endothelial cell growth factor (VEGF) is an endothelial cell-specific
      angiogenic and permeability-inducing factor that has been implicated in the
      pathogenesis of diabetic retinopathy. The objectives of this study are to compare
      VEGF and VEGF receptor expression between retinal and brain-derived endothelial
      cells cultured in 5 or 30 mM glucose for 5 days. Our results show that expression
      of cell-surface VEGF receptors, assessed by flow cytometry, is higher in retinal
      derived endothelial cells. RT-PCR results show that both retinal and brain
      derived endothelial cells express comparable levels and types of VEGF. Exposure
      to 30 mM glucose for 5 days did not alter levels of VEGF or VEGF receptors. The
      higher level of VEGF receptor expression in retinal endothelial cells suggests
      that the retinal microcirculation may be more sensitive to the effects of VEGF
      and this may contribute to the pathogenesis of diabetic retinopathy.

PMID- 12054528
TI  - GPI-anchored GFP signals Ca2+ but is homogeneously distributed on the cell
      surface.
AB  - Glycosyl-phosphatidylinositol (GPI)-anchored proteins are unique in that they
      penetrate only the outer leaflet of the plasma membrane but are still able to
      mediate intracellular signalling events following antibody-induced ligation.
      Detergent solubilisation studies suggest that microdomains exist at the cell
      surface within which are sequestered GPI-linked proteins. Here we report the
      construction and expression of a fluorescent GPI anchor on the surface of CHO,
      EL4, and U937 cells by fusing green fluorescent protein (GFP) to the GPI
      attachment site of CD59. The resultant GFP-GPI has properties comparable to that
      of endogenously expressed GPI-anchored molecules as shown by Triton X-114
      partitioning. However, sucrose gradient floatation showed that GFP-GPI was only
      partially resistant to detergent solubilisation. Furthermore confocal scanning
      laser microscopy revealed a homogeneous distribution of GFP-GPI at the cell
      surface, which only became clustered following cross-linking of the GPI anchor
      via an anti-GFP antibody. Surprisingly, GFP-GPI signalled Ca2+ change upon cross
      linking demonstrating its signalling competence. Our results suggest that the GPI
      anchor itself does not confer a clustered distribution to molecules but that
      clustering occurs following ligation with antibody, which allows the protein to
      become Ca2+ signalling competent.

PMID- 12054529
TI  - Human caspase 12 has acquired deleterious mutations.
AB  - Caspase 12 has been cloned from rodent cells, in which it mediated apoptosis in
      response to endoplasmic reticulum stress. Based on experiments with murine cells
      it was suggested that this caspase plays a central role in the pathogenesis of
      Alzheimer's disease. By alignment of the murine caspase 12 cDNA with the human
      genome sequence we localized the human caspase 12 gene at a single locus within
      the caspase 1/ICE gene cluster on chromosome 11q22.3. RT-PCR and molecular
      cloning revealed that nine alternatively spliced transcripts of this gene are
      expressed. A frame shift mutation and a premature stop codon which is present in
      all splice variants preclude the expression of a full length protein. An
      additional loss-of-function mutation within the SHG box, a critical site in
      caspases, prohibits any proteins, if they are produced, from acting
      catalytically. Based on our data we conclude that functional caspase 12 is lost
      in humans and that it can therefore not play a role in Alzheimer's disease.

PMID- 12054530
TI  - Ca2+-overload inhibits the cardiac SR Ca2+-calmodulin protein kinase activity.
AB  - There is increasing evidence to suggest that Ca2+-calmodulin dependent protein
      kinase (CaMK) regulates the sarcoplasmic reticulum (SR) function and thus plays
      an important role in modulating the cardiac performance. Because intracellular
      Ca2+-overload is an important factor underlying cardiac dysfunction in a heart
      disease, its effect on SR CaMK was examined in the isolated rat heart
      preparations. Ca2+-depletion for 5 min followed by Ca2+-repletion for 30 min,
      which is known to produce intracellular Ca2+-overload, was observed to attenuate
      cardiac function as well as SR Ca2+-uptake and Ca2+-release activities.
      Attenuated SR function in the heart was associated with reduced CaMK
      phosphorylation of the SR Ca2+-cycling proteins such as Ca2+-release channel,
      Ca2+-pump ATPase, and phospholamban, decreased CaMK activity, and depressed
      levels of SR Ca2+-cycling proteins. These results indicate that alterations in
      cardiac performance and SR function following the occurrence of intracellular
      Ca2+-overload may partly be due to changes in the SR CaMK activity.

PMID- 12054531
TI  - Two-hybrid cloning and characterization of OSH3, a yeast oxysterol-binding
      protein homolog.
AB  - We identify Osh3p, one of seven yeast oxysterol-binding protein (OSBP) homologs,
      by its protein-protein interactions with a DEAD-box RNA helicase, Rok1p. The ROK1
      gene was initially identified by its ability on a high-copy number plasmid to
      suppress the nuclear fusion defect caused by the kem1 null mutation. Our results
      show that OSH3 also affects nuclear fusion in a kem1-specific manner; the nuclear
      fusion defect of kem1 was intensified by the multicopy expression of OSH3. The
      Osh3p synthesis was highly induced by alpha-mating pheromone. We also found that
      OSH3 overexpression promoted filamentation growth of the Sigma1278b wild-type
      strain and suppressed the filamentation growth defect of the ste12 mutation.
      These results lead us to a new understanding of cellular functions of the yeast
      OSBPs.

PMID- 12054532
TI  - Identification of amidicin: a novel peptide with C-terminal amide structure
      isolated from porcine cardiac atrium.
AB  - Using a novel method employing a V8 protease digestion coupled with ethyl acetate
      extraction, we have purified a peptide with C-terminal amide structure from
      porcine cardiac atrium. The peptide was determined to be Ala-Val-Leu-Gly-Leu
      CONH2. According to the sequence, we have raised an antibody and established the
      radioimmunoassay. Using this radioimmunoassay, we have isolated a novel 14 amino
      acid peptide where C-terminus was amidated. This peptide was termed amidicin.
      Amidicin is widely distributed in porcine tissue and is especially abundant in
      pituitary gland, cardiac ventricle, and spleen.

PMID- 12054533
TI  - Chloroplast SecE: evidence for spontaneous insertion into the thylakoid membrane.
AB  - SecE, an essential component of the bacterial SecAYEG translocase, mediates
      protein translocation across the cytoplasmic membrane. In the thylakoid membranes
      of chloroplasts an SecE homologue, cpSecE, has recently been identified. In this
      report we show that insertion of cpSecE does not require stromal extract,
      indicating that signal recognition particle is not involved. Removal of
      nucleoside triphosphates has apparently no effect on the integration, again
      ruling out an involvement of SRP or its partner protein, FtsY. The use of well
      known inhibitors of the Sec- and Tat pathways, sodium azide and nigericin,
      respectively, also had no influence on membrane insertion. The data presented
      here point towards cpSecE as another passenger of a wholly spontaneous
      import/insertion pathway in the thylakoids of chloroplasts.

PMID- 12054534
TI  - Identification and characterization of Nek6 protein kinase, a potential human
      homolog of NIMA histone H3 kinase.
AB  - In Aspergillus nidulans, the kinase activity of NIMA (never in mitosis, gene A)
      is critical for the initiation of mitosis. NIMA regulates mitotic chromatin
      condensation through phosphorylation of histone H3 at serine 10. In the present
      study, we identified human Nek6 (hNek6), a member of the mammalian NIMA-related
      kinases. The predicted hNek6 protein is comprised of 338 amino acids. Northern
      blot analysis revealed that hNek6 transcripts are ubiquitously expressed with the
      highest expression found in the heart and skeletal muscle. Lower cell cycle
      dependent expression of hNek6 transcripts was observed in the early G1 phase. GFP
      fused hNek6 protein showed both nuclear and cytoplasmic localizations in HeLa
      cells. Fluorescence in situ hybridization using full-length hNek6 cDNA as a probe
      showed that the hNek6 gene is localized to human chromosome 9q33-34, a region at
      which the loss of heterozygosity is associated with transitional cell carcinomas.
      Importantly, recombinant hNek6 protein produced in insect cells effectively
      phosphorylated histones H1 and H3, but not casein. Thus, these results suggest
      that, unlike other mammalian NIMA-related kinases, Nek6 is a mitotic histone
      kinase which regulates chromatin condensation in mammalian cells.

PMID- 12054535
TI  - The carboxyterminus of the ATP-binding cassette transporter A1 interacts with a
      beta2-syntrophin/utrophin complex.
AB  - Recent work identified ABCA1 as the major regulator of plasma HDL-cholesterol
      responsible for the removal of excess choline-phospholipids and cholesterol from
      peripheral cells and tissues. ABCA1 function may depend on the association with
      heteromeric proteins and to identify these candidates a human liver yeast two
      hybrid library was screened with the carboxyterminal 144 amino acids of ABCA1.
      Beta2-syntrophin was found to interact with ABCA1 and the C-terminal five amino
      acids of ABCA1 proned to represent a perfect tail for binding to syntrophin PDZ
      domains. Immunoprecipitation further confirmed the association of ABCA1 and beta2
      syntrophin and in addition utrophin, known to couple beta2-syntrophin and its PDZ
      ligands to the F-actin cytoskeleton, was identified as a constituent of this
      complex. ABCA1 in the plasmamembrane of human macrophages was found to be
      partially associated with Lubrol rafts and effluxed choline-phospholipids involve
      these microdomains. Beta2-syntrophin does not colocalize in these rafts
      indicating that beta2-syntrophin may participate in the retaining of ABCA1 in
      cytoplasmic vesicles and for the targeting of ABCA1 to plasmamembrane
      microdomains when ABCA1 is released from beta2-syntrophin.

PMID- 12054537
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase-activating
      polypeptide inhibit the MEKK1/MEK4/JNK signaling pathway in endotoxin-activated
      microglia.
AB  - The vasoactive intestinal peptide (VIP) and the pituitary adenylate cyclase
      activating polypeptide (PACAP), two immunomodulatory neuropeptides, act as anti
      inflammatory factors for activated microglia, by inhibiting the production of
      proinflammatory factors. In the present study the effects of VIP/PACAP on the
      MEKK1/MEK4/JNK transduction pathway and on the subsequent changes in Jun family
      members, a transduction pathway clearly involved in the activation of microglia
      cells were examined. VIP/PACAP inhibit MEKK1 activity and the subsequent
      phosphorylations of MEK4, JNK, and c-Jun, which result in a decrease in the AP-1
      binding and a marked change in the composition of AP-1 complexes from c-Jun/c-Fos
      to JunB/c-Fos. Furthermore, VIP stimulates JunB production in LPS-stimulated
      microglia. Both inhibition of the MEKK1/MEK4/JNK pathway, leading to a reduction
      in phosphorylated c-Jun, and the stimulation of JunB are mediated through the
      specific VPAC1 receptor and cAMP/PKA pathway. The VIP/PACAP interference with the
      stress-induced SAPK/JNK pathway in activated microglia may represent a
      significant element in the regulation of inflammatory response in the CNS by
      endogenous neuropeptides.

PMID- 12054536
TI  - Down-regulation by elicitors of phosphatidylcholine-hydrolyzing phospholipase C
      and up-regulation of phospholipase A in plant cells.
AB  - Phosphatidylcholine, labeled by two fluorescent fatty acids, was fed to cultured
      plant cells (Petrosilenum crispum, L.; VBI-0, Nicotiana benthiana, L.) and
      fluorescent diacylglycerol (DAG) was the major metabolite. When a glycoprotein
      elicitor, derived from Phytophthora sojae, was applied to the parsley cells and
      the small protein cryptogein from Phytophthora cryptogea was applied to the
      tobacco cells, these signal substances strongly and rapidly decreased the pool of
      fluorescent diacylglycerol and weakly increased the pool of free fluorescent
      fatty acid and of fluorescent lysophosphatidylcholine. The cells responded in a
      very similar way to the application of mastoparan, a wasp venom peptide. As
      phosphatidic acid was only a very minor fluorescent metabolite DAG is
      hypothesized to arise by the action of a phosphatidylcholine-hydrolyzing
      phospholipase C which was down-regulated by elicitors. Up-regulation of a
      phospholipase A by elicitors is also suggested by these results. This is the
      first evidence for phosphatidylcholine-hydrolyzing phospholipase C in plant
      signal transduction.

PMID- 12054539
TI  - In silico sequence analysis of arylamine N-acetyltransferases: evidence for an
      absence of lateral gene transfer from bacteria to vertebrates and first
      description of paralogs in bacteria.
AB  - The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes
      responsible for the biotransformation of various arylamine and heterocyclic
      amines, including drugs and carcinogenic compounds. NAT and NAT-like genes have
      been identified in several vertebrate and eubacterial species. Little is known
      about their evolutionary history, but the horizontal transfer of NAT genes from
      bacteria to vertebrates was recently suggested [S. Salzberg, O. White, J.
      Peterson, J. Eisen, Science 292 (2001) 1903]. We used various bioinformatics
      based approaches to screen eukaryotic and prokaryotic genomes. We identified
      Mesorhizobium loti NAT genes as the first examples of NAT paralogs in
      prokaryotes. As shown for vertebrate species, the existence of NAT paralogs in
      this bacterium may be accounted for by enzymatic specialization after gene
      duplication. Phylogenetic analysis following the identification of a NAT ortholog
      in the nonvertebrate species Ciona intestinalis indicated that NAT genes are
      unlikely to be examples of direct horizontal gene transfer (HGT). Our study
      suggests that NAT genes have evolved from a common ancestor, with a succession of
      nonvertebrate intermediates. The absence of NAT genes in yeast, nematode worms,
      fruit flies, and mustard weed may result from gene loss in these nonvertebrate
      lineages. These results provide new insight into the taxonomic distribution and
      evolutionary history of this class of drug-metabolizing enzymes.

PMID- 12054538
TI  - Thapsigargin binds to and inhibits the cloned vanilloid receptor-1.
AB  - We investigated the effect of thapsigargin, a well-known sarcoplasmic reticulum
      ATPase (SERCA) inhibitor, on the non-specific Ca2+ channel vanilloid receptor-1
      (VR1) in CHO-VR1 cells. We found that thapsigargin inhibited the VR-1 mediated
      (45)Ca2+ uptake of CHO-VR1 cells (IC50=6.4+/-1.9 microM) and the [3H]RTX binding
      to VR1 (IC50=4.0+/-1.3 microM). Further analysis revealed that thapsigargin is a
      mixed-type inhibitor, suggesting both direct and indirect interactions between
      thapsigargin and the capsaicin binding site of VR1. Thapsigargin alone
      transiently elevated the [Ca2+]i in CHO-VR1 cells (EC50=44 nM). However, 45Ca2+
      uptake was not detected after thapsigargin treatment, indicating that the
      emptying of the thapsigargin sensitive intracellular pools of Ca2+ was
      responsible for the elevated [Ca2+]i level rather than the activation of VR-1. We
      conclude that thapsigargin represents a new prototype of a VR1 inhibitor and that
      caution should be exercised in interpreting the effects of thapsigargin,
      especially when it is used in the micromolar range to inhibit SERCA activity.

PMID- 12054540
TI  - Murine H-rev107 gene encoding a class II tumor suppressor: gene organization and
      identification of an Sp1/Sp3-binding GC-box required for its transcription.
AB  - H-rev107, which belongs to class II tumor suppressor genes, is ubiquitously
      expressed in normal cells, but is downregulated in many carcinomas and tumor cell
      lines. Sequence analysis showed that the murine H-rev107 gene is composed of five
      exons and four introns. Transfections revealed that 7.6 kb of the H-rev107
      promoter directed a high level expression of the reporter gene. There were no
      significant differences in promoter activity when various 5'-deletion promoter
      constructs from -7.6 kb to -113 bp were employed. By further deletion and
      mutation analysis, we found that the region between -83 and -75 containing a GC
      box was essential for promoter activity in NIH3T3 or REF52 fibroblasts expressing
      H-rev107 at moderate to high levels. Gelshifts demonstrated in vitro binding of
      Sp1 and Sp3 to this GC-box. Cotransfection of Sp1 and Sp3 functionally stimulated
      promoter activity in SL2 cells. By chromatin immunoprecipitation assays, we
      observed in vivo binding of Sp1 and Sp3 to the proximal promoter region in NIH3T3
      cells and liver, concluding that the transcription of the H-rev107 gene is
      dependent on Sp1/Sp3-binding to the -83/-75 GC-box.

PMID- 12054542
TI  - Overexpression of Arabidopsis response regulators, ARR4/ATRR1/IBC7 and
      ARR8/ATRR3, alters cytokinin responses differentially in the shoot and in callus
      formation.
AB  - Arabidopsis ARR4/ATRR1/IBC7 and ARR8/ATRR3 are homologous genes of prokaryotic
      response regulators that are involved in the His-Asp phosphorelay signal
      transduction. We analyzed the function of these genes as response regulators
      using transgenic plants. Overexpression of ARR4 in cultured stems of the
      transgenics markedly promoted shoot formation in the presence of cytokinin, while
      overexpression of ARR8 repressed shoot formation and greening of calli. The
      expression level of cytokinin-inducible genes, cycD3 and cab increased in the
      ARR4 overexpressor but decreased in the ARR8 overexpressor. By contrast, two
      drought stress-inducible genes, rd29A and erd1, were expressed in both
      overexpressors as that in control plants. These results suggest that ARR4 and
      ARR8 are involved in cytokinin signal transduction, and that ARR4 functions as a
      positive-regulator, whereas ARR8 functions as a negative-regulator. Furthermore,
      microarray analysis showed that several genes were up-regulated in the ARR4
      overexpressor. Consistent with these results, ARR4 and ARR8 might play important
      roles in the sensoring system of cytokinin signal transduction pathway in various
      developmental and environmental conditions and the regulation of gene expression.

PMID- 12054541
TI  - A secreted form of human ADAM9 has an alpha-secretase activity for APP.
AB  - ADAM9 (MDC9, meltrin gamma) is a member of the ADAM family of metalloproteases,
      which play important roles in cell-cell fusion, intracellular signaling, and
      other cellular functions. Here we cloned a novel form of human ADAM9, designated
      hADAM9s (s for short), which lacks the carboxyl-terminus. Human ADAM9s was found
      to be secreted from transfected COS cells. RT-PCR analysis demonstrated that the
      mRNA for hADAM9s is expressed in human brain, liver, heart, kidney, lung, and
      trachea. When hADAM9s was co-expressed in COS cells with APP and treated with
      phorbol ester, the APP was digested exclusively at the alpha-secretory site.
      These results suggest that hADAM9s has an alpha-secretase-like activity for APP.
      Non-amyloidgenic cleavage of APP may occur at the plasma membrane. Our new
      results support a new therapeutic strategy to decrease in the Abeta content by
      directly activating ADAM9 in the extracellular space.

PMID- 12054543
TI  - Identification and characterization of a novel murine multigene family containing
      a PHD-finger-like motif.
AB  - The genes Phf5a and Phf5b-ps are the first two members of a novel murine
      multigene family that is highly conserved during evolution and belongs to the
      superfamily of PHD-finger genes. The Phf5 gene family contains an active locus on
      mouse chromosome 15, region E and several processed pseudogenes on different
      chromosomes. The active locus, Phf5a, is expressed ubiquitously in pre- and
      postnatal murine tissues and encodes a protein of 110 amino acids. The protein is
      localized in the nucleus in a non-homogenous pattern as the nucleolar
      subcompartment is almost free of Phf5a. The molecular and biological functions of
      Phf5a are unknown up-to-date, but the systematic deletion of its yeast homolog is
      lethal, pointing out that the protein is required for cell viability.
      Interpretation of our data and review of the literature suggest both basic and
      essential cellular functions of the Phf5a protein, possibly acting as a chromatin
      associated protein.

PMID- 12054544
TI  - Butyrate reduces colonic paracellular permeability by enhancing PPARgamma
      activation.
AB  - Butyrate may have a role in preventing ulcerative colitis, but its precise
      mechanism is unknown. Also, PPARgamma (peroxisome proliferator-activated receptor
      gamma) is expressed at high levels both in the colonic epithelium and colon
      cancer cell lines, but no report was shown on the relationship between PPARgamma
      activation and the effect of butyrate. We investigated the effects of butyrate
      and PPARgamma agonist on paracellular permeability. To discover whether PPARgamma
      expressed in the cell lines treated with butyrate was functional or not, we
      transfected HT-29 cells with an acyl-CoA oxidase promoter-luciferase reporter
      plasmid containing a PPRE (peroxisome proliferator responsive element) and
      analyzed the luciferase activity. Butyrate and PPARgamma agonist significantly
      reduced paracellular permeability of the colon cell line (p<0.05) and this effect
      indicated that butyrate and PPARgamma agonist decreased HT-29 cell growth and
      increased differentiation (p<0.01). PPRE activation treated with butyrate was
      approximately four and a half times that in untreated cells (p<0.01). These
      findings suggest that the effect of butyrate on paracellular permeability has
      apparently taken place through PPARgamma activation and this effect attributes to
      preventing inflammation of the colon.

PMID- 12054545
TI  - The mediation of veratryl alcohol in oxidations promoted by lignin peroxidase:
      the lifetime of veratryl alcohol radical cation.
AB  - The kinetics of decay of veratryl alcohol radical cation, generated by cerium(IV)
      ammonium nitrate induced oxidation of veratryl alcohol, have been followed
      spectrophotometrically in a stopped-flow apparatus. In acidic aqueous
      acetonitrile the radical cation was found to decay by a first-order process, due
      to deprotonation from the alpha-carbon leading to an alpha-hydroxybenzyl radical
      with the rate constant of 17.1+/-0.5 s(-1). This value is in full agreement with
      those obtained by pulse radiolysis studies but much lower than the value
      (1.2x10(3) s(-1)) indirectly determined by EPR experiments. The implications of
      these results with respect to the possible role of veratryl alcohol as a mediator
      in the oxidative biodegradation of lignin catalysed by lignin peroxidase are
      discussed.

PMID- 12054546
TI  - Reduction of actin-related protein complex 2/3 in fetal Down syndrome brain.
AB  - Down syndrome (DS) patients present with morphological abnormalities in brain
      development, leading to mental retardation. Given the importance of actin
      cytoskeleton to form the basis of various cell functions, the regulation of actin
      system is crucial during brain development. We therefore aimed to study the
      expression levels of actin binding proteins in fetal DS and control cortex. We
      evaluated the levels of eight actin binding proteins using the proteomic approach
      of two-dimensional gel electrophoresis with subsequent mass spectroscopical
      identification of protein spots. In fetal DS brain we found a significant
      reduction of the actin-related protein complex 2/3 (Arp2/3) 20 kDa subunit and
      the coronin-like protein p57, which are involved in actin filament cross-linking
      and nucleation and capping of actin filaments. We conclude that deficient levels
      of these proteins may, at least partially, be involved in the dysgenesis of the
      brain in DS.

PMID- 12054547
TI  - Insulin-secreting INS-1 cells generate a novel type of poorly synchronized Ca2+
      transients.
AB  - Pancreatic beta-cells have an intrinsic oscillatory Ca2+ activity supposed to be
      synchronized among the islets by cytoplasmic Ca2+ transients elicited by
      nonadrenergic, noncholinergic (NANC) neurons. To improve the understanding of
      this process, the cytoplasmic Ca2+ concentration ([Ca2+]i) was measured in two
      insulin-releasing cell lines using dual wavelength microfluorometry and the
      indicator fura-2. INS-1 cells but not RINm5F cells were found to generate
      transients of [Ca2+]i in the presence of the Ca2+ channel blocker
      methoxyverapamil. These transients differed from those occurring in native beta
      cells persisting in the presence of thapsigargin or during prolonged exposure to
      ATP. Moreover, the [Ca2+]i transients were poorly synchronized whether or not the
      INS-1 cells had physical contact. If appearing in native beta-cells, the type of
      [Ca2+]i transients now observed may interfere with the coordination of the beta
      cell rhythmicity evoked by NANC neurons.

PMID- 12054548
TI  - Azaftig stimulates in vitro lipolysis by rodent and human adipocytes.
AB  - Azaftig is an urinary proteoglycan present in some cancer and AIDS patients
      experiencing weight loss. Administration of azaftig to mice results in weight
      loss that is associated with loss of fat depot. So far, very little is known
      about the mechanism underlying loss of fat depot in mice or weight loss in
      patients excreting azaftig. Augmentation of lipolysis may be one mechanism that
      can cause reduction of fat depot. Therefore, the present study was designed to
      examine the effect of azaftig on lipolysis by adipocytes derived from obese rats
      and humans. Results show a dose-dependent potentiation of lipolysis by azaftig in
      both rat and human adipocytes.

PMID- 12054549
TI  - Comparison of anti-p53 antibodies in immunoblotting.
AB  - Some of the most important tools to study p53 protein are various anti-p53
      antibodies and immunological methods based on antibody-antigen reactions.
      Critical comments on the specificity and sensitivity of anti-p53 antibodies have
      been published. Four monoclonal and two polyclonal anti-p53 antibodies, four of
      them from two different sources, were compared for their ability to detect in
      immunoblotting the benzo(a)pyrene-induced p53 from C57BL/6 mouse skin and MCF-7
      human breast carcinoma cells. Multiple extra bands were seen with most
      antibodies. A theoretical comparison of the equivalent epitopes of p53 homologues
      with the known epitopes of p53 antibodies indicated that the extra bands seen
      with most antibodies are not due to cross-reactivity with these homologues. A
      careful adjustment of antibody dilutions is needed for each application utilizing
      commercial p53 antibodies, regardless of the recommendations of the supplier.

PMID- 12054550
TI  - A novel and potent ribonuclease from fruiting bodies of the mushroom Pleurotus
      pulmonarius.
AB  - A ribonuclease (RNase), with an N-terminal sequence different from those of
      ribonucleases from the mushrooms Irpex lacteus, Lentinus edodes, Pleurotus
      ostreatus, Pleurotus tuber-regium, and Volvariella volvacea, was purified from
      fruiting bodies of the edible mushroom Pleurotus pulmonarius. The N-terminal
      sequence of P. pulmonarius RNase manifested homology to a portion of the
      sequences of ribosome inactivating protein abrin-b, abrin-c, and abrin-d, and
      Bacillus subtilis transcriptional regulator. The ribonuclease was adsorbed on
      Affi-gel blue gel, CM-Sepharose, and Mono S. It displayed a molecular mass of
      14.4 kDa in both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      gel filtration on Superdex 75. The ribonuclease exhibited an activity of 25 114
      U/mg on yeast tRNA. The highest ribonucleolytic activity was demonstrated toward
      poly C, followed by poly A, and then by poly G. There was no activity toward poly
      U. The optimal pH for its activity was 7 and the optimal temperature was 55
      degrees C. It inhibited cell-free translation in a rabbit reticulocyte lysate
      with an IC50 of 0.33 nM.

PMID- 12054552
TI  - Revised theory on DNA renaturation kinetics and its experimental verification.
AB  - Many molecular biology and genomics techniques (including C(0)t analysis, PCR,
      and HPLC) depend upon the renaturation of DNA in solution. Traditionally, the
      renaturation process has been treated as a second-order kinetics reaction with
      the concentration of the DNA as the order parameter. However, second-order
      kinetics only describes complementary strand recognition and not the
      intramolecular "zipping" of complementary strands once recognition has been
      established. And also we cannot use simply the DNA concentration as the order
      parameter. Here I present an improved model that takes both phenomena into
      account using "mol-bases" as the order parameter. The model was tested
      experimentally and found to provide a more accurate description of the observed
      data than previous DNA renaturation models based solely on second-order kinetics.

PMID- 12054551
TI  - Cloning, sequencing, and expression analysis of the porcine uroplakin II gene.
AB  - In this study, we report the cloning of porcine UPII genomic DNA, which contains
      a putative full-length open reading frame encoding the UPII protein. A comparison
      of the porcine UPII gene coding sequence with the previously published mouse UPII
      sequence demonstrates that the exon sequences are only partially conserved.
      Northern and immunohistochemical analyses show that the porcine UPII gene is
      expressed only in the urothelium and that the protein specifically localizes to
      urothelial superficial cells. Among urothelial superficial cells, 8.5-9.8% of
      umbrella cells expresses the UPII gene. A 2-kb region of the porcine UPII
      promoter contains multiple transcription factor binding sites, including GC
      boxes, SP1, AP2, and GATA-box sites, but no TATA or CAAT-box sequences. A
      sequence comparison of the porcine and murine UPII promoter genes by the MEME
      system allowed two conserved motifs to be identified, suggesting that these
      sequences have cis-acting regulatory roles. Sequence homologies between the
      motifs A and B of the two species are 79% and 80%, respectively, although their
      relative locations are different. Our results show that the porcine UPII gene is
      expressed highly and specifically in the bladder urothelium.

PMID- 12054554
TI  - Farnesol as an inhibitor and substrate for rabbit liver microsomal P450 enzymes.
AB  - Farnesol and the related isoprenoids, geranylgeraniol, geranylgeranyl
      pyrophosphate, and farnesyl pyrophosphate, are produced in the endoplasmic
      reticulum of hepatocytes in mammals, and each serve important biological
      functions. Of these compounds, only farnesol was shown to significantly inhibit
      rabbit liver microsomal cytochrome P450 enzymes. The observed inhibition appeared
      to be reversible, and was not strictly competitive, but rather mixed in nature.
      Of the activities examined, ethoxycoumarin de-ethylase and diclofenac-4
      hydroxylase activities were most sensitive to farnesol, with K(I) and K(I)'
      values between 11 and 40 microM. Caffeine-8-hydroxylation and taxol-6
      hydroxylation were not inhibited at all by farnesol. Farnesol appeared to be a
      P450 substrate, as well as an inhibitor, as indicated by the NADPH-dependent
      decrease in farnesol concentration in microsomal incubations, and the metabolism
      was inhibited by CO, which pointed to the involvement of P450 isozymes.

PMID- 12054553
TI  - A novel photoprotein from oceanic squid (Symplectoteuthis oualaniensis) with
      sequence similarity to mammalian carbon-nitrogen hydrolase domains.
AB  - A 60-kDa photoprotein was selectively extracted from squid photogenic organ with
      0.6 M KCl solution at pH 6 as luminescence-active forms. The photoprotein with
      fluorescence chromophore was eluted from size-exclusion HPLC mainly as oligomeric
      forms (about 200 kDa or more) with a trace amount of monomeric form of about 60
      kDa. A limited tryptic digestion of the KCl-extract induced the cleavage into a
      40-kDa fragment and a 16-kDa N-terminal fragment and the conversion to the
      monomeric form which still retained luminescence activity. Under UV light the 60
      kDa protein and its 40-kDa fragment emitted fluorescence. Immunoblot analysis
      using specific antibody showed specific expression of the 60-kDa protein in the
      photogenic organ. Amino acid sequences of the 60-kDa photoprotein, its 40- and 16
      kDa fragments, and six peptides from the Lys-C digest revealed no sequence
      similarity to known photoproteins but significant similarity to the carbon
      nitrogen hydrolase domain found in mammalian biotinidase and vanin
      (pantetheinase).

PMID- 12054555
TI  - Decreased subunit exchange of heat-treated lens alpha A-crystallin.
AB  - alpha A-Crystallin high-molecular-weight (HMW) aggregates were prepared by
      preheating at 80-90 degrees C and studied using spectroscopic measurements.
      Conformational differences were suggested based on data of increased bis-ANS
      (4,4(')-dianilino-1,1(')-binaphthalene-5,5(')-disulfonic acid) and ThT
      (thioflavin T) fluorescence as well as increased far-UV and decreased near-UV
      circular dichroism (CD). These results indicated that HMW aggregated alpha
      crystallin was more hydrophobic than the native alpha-crystallin, possibly
      resulting from partial unfolding of alpha-crystallin. The two cysteines in alpha
      A-crystallin were mostly oxidized in HMW aggregates. The effects of HMW
      aggregation on the dynamic structure were studied with fluorescence resonance
      energy transfer; subunit exchange became slower. These results strongly suggest
      that HMW alpha A-crystallin aggregates result from exposure of buried beta
      pleated sheets and increased hydrophobic interaction.

PMID- 12054556
TI  - A single nucleotide polymorphism in the promoter region of the human gene for
      osteoprotegerin is related to vascular morphology and function.
AB  - Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor
      family, and has previously been shown to regulate bone mass by inhibiting
      osteoclast differentiation and activation. Recent evidence indicates that OPG
      also plays a role in the vascular system, since ablation of the OPG gene in mice
      results in calcification of the aorta and renal arteries, and association has
      been found between serum levels of OPG and cardiovascular mortality. This study
      presents a novel single nucleotide polymorphism, a T/C transition located 129 bp
      upstream the TATA-box of the human OPG gene, detected by sequence analysis. The
      OPG genotype was determined by restriction fragment length polymorphism in a
      cohort consisting of 59 healthy subjects. The intima-media thickness (IMT) in the
      common carotid artery and maximal post-ischemic forearm blood flow (FBF) were
      investigated. Subjects with the CC genotype showed a significantly increased IMT
      (p<0.05) and a concommitantly reduced maximal FBF (p<0.01) as compared to those
      with the T allele. Thus, our results show that the polymorphism in the promoter
      region of OPG is associated with both vascular morphology and function in
      apparently healthy subjects.

PMID- 12054557
TI  - A two step model aimed at delivering antisense oligonucleotides in targeted
      cells.
AB  - To be efficient in vivo antisense oligonucleotides must reach the targeted cells
      and then cross the cellular membrane. We propose a two step system where the
      oligonucleotide is first electrostatically bound to a peptide coupled to a ligand
      of a cellular receptor. A complex is formed which allows the oligonucleotide to
      be bound to the membrane of the targeted cells. These oligonucleotides are then
      delivered inside the cells by the subsequent use of a transfection agent. As a
      reductionist model of peptide coupled to a ligand we have used a lipopeptide and
      characterized by a filter elution assay the stoichiometry between the peptide and
      the oligonucleotide in the complexes. Using HeLa cultured cells we have shown
      that addition of these complexes to the cells triggers the oligonucleotide
      binding to the cell membrane. The subsequent addition of dendrimers allows these
      antisense oligonucleotides to inhibit a reporter gene inside the cells.

PMID- 12054558
TI  - Evolution of placentally expressed cathepsins.
AB  - Species and strain variants of a family of placentally expressed cathepsins
      (PECs) were cloned and sequenced in order to identify evolutionary conserved
      structural characteristics of this large family of cysteine proteases. Cathepsins
      M, P, Q, and R, are conserved in mice and rats but homologs of these genes are
      not found in human or rabbit placenta, showing that this family of proteases are
      probably restricted to rodents. Species-specific gene duplications have given
      rise to variants of cathepsin M in mice, and cathepsin Q in rats. Although the
      PECs have diverged at a greater rate than the other lysosomal cathepsins,
      residues around the specificity sub-sites of the individual enzymes are
      conserved. Strain-specific polymorphisms show that the evolutionary rate of
      divergence of cathepsins M and 3, the most recently duplicated pair of mouse
      genes, is even higher than the other PECs. In human placenta, critical functions
      of the PECs are probably performed by broader specificity proteases such as
      cathepsins B and L.

PMID- 12054559
TI  - Splice variants of the beta-site APP-cleaving enzyme BACE1 in human brain and
      pancreas.
AB  - BACE is the beta-secretase responsible for the first step in amyloidogenic
      processing of the amyloid precursor protein APP. We have identified two BACE
      isoforms, BACE1B and BACE1C, lacking 25 and 44 amino acids, respectively. Whereas
      the BACE1B transcript is present in human pancreas and brain, the BACE1C
      transcript is found in pancreas only. In transfected cells both BACE1A, which
      encodes the originally described full-length BACE1 protein and the close homolog
      BACE2 localized mainly to post-Golgi membranes. In contrast, the two shorter
      isoforms were found in the endoplasmic reticulum only, and they did not display
      beta-secretase activity. Using RNase protection we in addition show that the
      major pancreatic transcript is BACE1A. This suggests that the known absence of
      beta-secretase activity in the pancreas is not due to a missing BACE1A
      transcript.

PMID- 12054560
TI  - Osteoprotegerin differentially regulates protease expression in osteoclast
      cultures.
AB  - Cysteine proteases and matrix metalloproteinases (MMPs) are important factors in
      the degradation of organic matrix components of bone. Osteoprotegerin (OPG) is an
      osteoblast-secreted decoy receptor that inhibits osteoclast differentiation and
      activation. This study investigated the direct effects of human OPG on cathepsin
      K, MMP-9, MMP-2, and tissue inhibitors of metalloproteinases (TIMP1 and TIMP2)
      expressed by purified rabbit osteoclasts. The expression of two osteoclast
      markers, namely tartrate-resistant acid phosphatase (TRAP) and cathepsin K, was
      inhibited by 100 ng/mL hOPG, whereas MMP-9 expression was enhanced. Gelatinase
      activities were measured using a zymographic assay, and hOPG was shown to enhance
      both pro-MMP-9 and MMP-2 activities. Concomitantly, TIMP1 expression was greatly
      stimulated by hOPG, whereas TIMP2 mRNA levels were not modulated. Overall, these
      results show that hOPG regulates the proteases produced by purified osteoclasts
      differentially, producing a marked inhibitory effect on the expression of
      cathepsin K, the main enzyme involved in bone resorption.

PMID- 12054561
TI  - Role of the second immunoglobulin-like loop of nectin in cell-cell adhesion.
AB  - Nectin is a Ca(2+)-independent immunoglobulin (Ig)-like cell-cell adhesion
      molecule that forms cell-cell adherens junctions cooperatively with E-cadherin in
      a variety of cells. Nectin has one transmembrane segment and three Ig-like loops
      in the extracellular region. The first Ig-like loop is essential for the trans
      dimer formation of nectin of two neighboring cells, causing cell-cell adhesion.
      We show here that the second Ig-like loop is essential for the cis-dimer
      formation of nectin on the same cell, and that the cis-dimer formation is
      essential for the trans-dimer formation.

PMID- 12054562
TI  - Binding properties of a locust's chemosensory protein.
AB  - The chemosensory protein CSP-sg4 of the desert locust Schistocerca gregaria binds
      reversibly N-phenyl-1-naphthylamine in fluorescent-binding assays, with a
      dissociation constant of 4 microM. Upon binding to the protein, the emission
      peaks of the fluorescent probe undergo a marked blue shift, accompanied by an
      order of magnitude increase of the maximum intensity. The assay has also allowed
      the measurement of the affinity of CSP to other aromatic and aliphatic compounds.
      The binding capacity of this protein is unaffected by thermal treatments up to
      100 degrees C for 20 min. The ligand-binding characteristics of chemosensory
      proteins may help in clarifying the role of this recently discovered class of
      soluble proteins in chemoreception.

PMID- 12054563
TI  - The amino-terminal region of insulin-like growth factor binding protein-3, (1
      95)IGFBP-3, induces apoptosis of MCF-7 breast carcinoma cells.
AB  - In an earlier study, we reported that an N-terminal proteolytic fragment ((1
      95)IGFBP-3) corresponding to the first 95 residues of human insulin-like growth
      factor binding protein-3 (IGFBP-3) inhibits proliferation in a variety of
      fibroblasts. With a view to investigating its cytostatic capacity in carcinoma
      cells, we transiently transfected MCF-7 breast adenocarcinoma cells with an
      expression vector containing (1-95)IGFBP-3 cDNA. The transfected cells secreted a
      hyper-glycosylated form of (1-95)IGFBP-3. Twenty-four hours after transfection,
      cell morphology and viability were similar in control and (1-95)IGFBP-3-secreting
      cells. However, after 48 h, (1-95)IGFBP-3-secreting cells were apoptotic, with
      marked cytoplasmic vacuolation and increased free histones in the cytoplasm.
      Culture media conditioned by (1-95)IGFBP-3-secreting cells also induced
      morphological changes and apoptosis in wild-type MCF-7 cells, indicating that (1
      95)IGFBP-3 was responsible for the effects observed. These results provide
      further evidence that the N-terminal proteolytic fragment of IGFBP-3 has a
      functional role.

PMID- 12054564
TI  - Lack of matrix metalloproteinase (MMP)-1 and -3 expression in Ewing sarcoma may
      be due to loss of accessibility of the MMP regulatory element to the specific
      fusion protein in vivo.
AB  - Ewing sarcoma is a malignant bone and soft tissue tumor of children and young
      adults, which is known to be highly aggressive and invasive. It expresses
      specific chimeric genes (EWS-FLI-1, EWS-ERG, EWS-ETV1, and EWS-E1AF), the 3'
      portions of which are all members of the ETS family. ETS-related proteins, such
      as FLI-1, ERG, and E1AF, transactivate the promoters of matrix metalloproteinase
      (MMP) genes, which play important roles in the processes of invasion and
      metastasis. Therefore, we hypothesize that the Ewing sarcoma-specific chimeric
      genes also transactivate the MMP genes, contributing to the tumor's invasiveness
      and propensity for metastasis. To verify this hypothesis, we investigated the
      expression of MMPs in eight Ewing sarcoma cell lines. Surprisingly, MMP-1 and MMP
      3 were not expressed at all in any of the cell lines. MMP-9 was expressed in four
      out of the eight cell lines, and MMP-2 and MT1-MMP in all of the cell lines.
      Ewing sarcoma-specific chimeric genes have been shown to transactivate the
      promoter of the MMP-1 gene by the reporter assay, and bind to the putative
      recognition sites in the MMP regulatory elements by the gel shift assay. However,
      an in vivo formaldehyde cross-linking study revealed that the chimeric protein
      did not bind to the predicted ETS recognition sites in the regulatory elements of
      the MMPs. These results indicate that the absence of the MMP expression in the
      tumor cells is at least in part due to the loss of accessibility of the ETS
      recognition sites in the regulatory elements of the MMP genes. Therefore, we
      should be careful before theorizing simply that a putative binding site is
      essential for the transcription of critical genes, since the binding of this
      fusion protein was found to be modulated in tumor cells in this study.

PMID- 12054565
TI  - Inhibitors of the tyrosine kinase signaling cascade attenuated thrombin-induced
      guinea pig airway smooth muscle cell proliferation.
AB  - Airway remodeling is one of the major hallmarks of asthma. The present study
      examined the effects of tyrosine kinase inhibitors on thrombin-induced guinea pig
      ASM cell proliferation, in comparison with inhibitors of mitogen-activated
      protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K). The ASM cells
      expressed smooth muscle alpha-actin and myosin, and responded to thrombin by
      increasing cytosolic Ca(+2). Thrombin (1-10 U/ml) induced [(3)H]thymidine
      incorporation into ASM cells. Tyrphostin 47, a broad-spectrum tyrosine kinase
      inhibitor, PP2, a Src-specific inhibitor, and piceatannol, a Syk-selective
      inhibitor, significantly attenuated thrombin-induced [(3)H]thymidine
      incorporation. In addition, the tyrosine kinase inhibitors significantly reduced
      thrombin-induced cyclin D(1) expression in ASM cells. PD098059 and U0126, two
      MAPK kinase inhibitors, and LY294002, a PI3K inhibitor, significantly blocked
      thrombin-induced [(3)H]thymidine incorporation and cyclin D(1) expression in ASM
      cells. Our data show that inhibitors of Src and, probably Syk, can modulate
      thrombin-induced ASM cell proliferation, which may have therapeutic potential for
      asthma.

PMID- 12054566
TI  - GDH1 expression is regulated by GLN3, GCN4, and HAP4 under respiratory growth.
AB  - In the yeast Saccharomyces cerevisiae, two NADP(+)-dependent glutamate
      dehydrogenase isoenzymes encoded by GDH1 and GDH3 catalyze the synthesis of
      glutamate from ammonium and alpha-ketoglutarate. In this work we analyzed GDH1
      transcriptional regulation, in order to deepen the studies in regard to its
      physiological role. Our results indicate that: (i) GDH1 expression is strictly
      controlled in ethanol-grown cultures, constituting a fine-tuning mechanism that
      modulates the abundance of Gdh1p monomers under this condition, (ii) GDH1
      expression is controlled by transcriptional activators that have been considered
      as exclusive of either nitrogen (Gln3p and Gcn4p) or carbon metabolism (HAP
      complex), and (iii) chromatin remodeling complexes play a role in GDH1
      expression; ADA2 and ADA3 up-regulated GDH1 expression on ethanol, while that on
      glucose was ADA3-dependent. SPT3 and SNF2 activated GDH1 expression on either
      carbon source whereas GCN5 played no role in any condition tested. The above
      described combinatorial control results in a refined mechanism that coordinates
      carbon and nitrogen utilization.

PMID- 12054567
TI  - Adhesion of osteosarcoma cells to the 70-kDa core region of thrombospondin-1 is
      mediated by the alpha 4 beta 1 integrin.
AB  - Thrombospondin-1 (TSP-1) is an extracellular glycoprotein that is involved in a
      variety of physiological processes such as tumor cell adhesion, invasion, and
      metastasis. It has been hypothesized that TSP-1 provides an adhesive matrix for
      osteosarcoma cells. Here we present data showing that TSP-1 can promote cell
      substrate adhesion to U2OS and SAOS cells through the alpha 4 beta 1 integrin.
      The dose-dependent adhesion to TSP-1 was inhibited by anti-integrin antibodies
      directed against the alpha 4 or beta 1 subunit, but not by control antibodies
      against other integrins. To localize the potential alpha 4 beta 1-binding site
      within the TSP-1 molecule, the protein was subjected to limited proteolysis with
      chymotrypsin in the absence of calcium. The stable 70-kDa core fragment produced
      under these conditions promoted alpha 4 beta 1-dependent osteosarcoma cell
      adhesion in a manner similar to that of the intact protein. Moreover adhesion
      experiments with neutralizing antibodies revealed that the adhesion was totally
      dependent on the alpha 4 beta 1 interaction. Further blocking experiments with
      potential inhibitory peptides revealed that the alpha 4 beta 1-mediated adhesion
      was not influenced by peptides containing the RGD sequence. Attachment to the 70
      kDa fragment was strongly inhibited by the CS-1 peptide, which represents the
      most active recognition domain for alpha 4 beta 1 integrin in fibronectin. The
      present data provide evidence that TSP-1 contains an alpha 4 beta 1 integrin
      binding site within the 70-kDa core region.

PMID- 12054568
TI  - WAVE2 serves a functional partner of IRSp53 by regulating its interaction with
      Rac.
AB  - We previously reported that IRSp53 binds both Rac and WAVE2, inducing formation
      of Rac/IRSp53/WAVE2 complex that is important for membrane ruffling. However,
      recent reports noted a specific interaction between IRSp53 and Cdc42 but not Rac,
      which led us to re-examine the binding of IRSp53 to Rac. Immunoprecipitation
      analysis and pull-down assay reveal that full-length IRSp53 binds Rac much less
      efficiently than the N-terminal fragment, which may be caused by intramolecular
      interaction. Interestingly, the intramolecular interaction is interrupted by the
      binding of WAVE2 and full-length IRSp53 associates with Rac in the presence of
      WAVE2. We also report that IRSp53 induces spreading and neurite formation of N1E
      115 cells, which presumably reflect functional cooperation with Rac.

PMID- 12054569
TI  - In vitro and in vivo hepatic transport of the magnetic resonance imaging contrast
      agent B22956/1: role of MRP proteins.
AB  - The molecular mechanisms of the hepatic transport of B22956/1, a new gadolinium
      complex from the class of intravascular contrast agents for MRI, which undergoes
      extensive biliary elimination, were studied. Biliary and urinary elimination of
      B22956/1 were measured in normal and in mutant MRP2 lacking rats (TR(-));
      cellular trafficking of the compound was assessed in wild and MRP1 or MRP2
      transfected MDCKII cells. Eight hours after IV injection of B22956/1, 90+/-8% of
      the dose was recovered in the bile of normal rats. By contrast, in TR(-) rats,
      the biliary excretion was significantly lower (14+/-3%) while 55+/-9% of the
      compound was found in urine. In vitro, the cellular accumulation of B22956/1 was
      significantly lower in both MRP1 and MRP2 transfected cells as compared to wild
      type MDCKII cells, and the cellular efflux was prevented by the MRP inhibitor
      MK571, indicating the involvement of both MRP2 and MRP1 in the transport of
      B22956/1. Due to the distinct cellular localization of the proteins, MRP2
      accounts for the biliary and urinary excretion of the compound, while MRP1
      prevents cellular accumulation of the MRI agent. B22956/1 may be useful in
      clinical conditions where a defective biliary transport is present.

PMID- 12054570
TI  - The preovulatory rise of ovarian ornithine decarboxylase is required for
      progesterone secretion by the corpus luteum.
AB  - Ovarian progesterone secretion during the diestrus stage of the estrous cycle is
      produced by luteal cells derived from granulosa and thecal cells after the
      differentiation process that follows ovulation. Our results show that blockade of
      the preovulatory rise of ovarian ornithine decarboxylase (ODC), a key enzyme in
      polyamine biosynthesis, by treatment with the specific inhibitor alpha
      difluoromethylornithine (DFMO) leads to a significant decrease in the ovarian
      progesterone content and a dramatic fall in the plasma levels of this hormone
      during the following diestrus. The same inhibition was produced in spite of the
      fact that both luteinizing and follicle stimulating hormones were given
      concomitantly with DFMO. On the other hand, the acute rise in the plasma
      progesterone levels observed after administration of human chorionic gonadotropin
      to mice at different periods of the estrous cycle was not affected by DFMO
      administration. Our results indicate that although elevated levels of ODC are not
      required for acute ovarian steroidogenesis, the preovulatory peak of ovarian ODC
      activity observed in the evening of proestrus may be critical for the
      establishment of a constitutive steroidogenic pathway and progesterone secretion
      by the corpus luteum during the diestrus stage of the murine estrous cycle.

PMID- 12054571
TI  - Increased MAPK signaling during in vitro muscle wounding.
AB  - Regeneration of skeletal muscle upon injury is a complex process, involving
      activation of satellite cells, followed by migration, fusion, and regeneration of
      damaged myofibers. Previous work concerning the role of the mitogen activated
      protein (MAP) kinase signaling pathways in muscle injury comes primarily from
      studies using chemically induced wounding. The purpose of this study was to test
      the hypothesis that physical injury to skeletal muscle cells in vitro activates
      the MAP kinase signaling pathways. We demonstrate that extracellular signal
      regulated kinases (ERKs) 1, 2, and p38 are rapidly and transiently activated in
      response to injury in C2C12 cells, and are primarily localized to cells adjacent
      to the wound bed. Culture medium from wounded cells is able to stimulate
      activation of p38 but not ERK in unwounded cells. These results suggest that both
      ERK and p38 are involved in the response of muscle cells to physical injury in
      culture, and reflect what is seen in whole tissues in vivo.

PMID- 12054572
TI  - Identification of the regulatory region required for ubiquitination of the cyclin
      kinase inhibitor, p21.
AB  - The expression of cyclin kinase inhibitor p21 is regulated by the ubiquitin
      proteasome protein degradation system, as well as by transcriptional regulation.
      Generally, ubiquitination is regulated by the phosphorylation of the substrate.
      In this study, we identified the region of p21 responsible for the regulation of
      ubiquitination. Since the phosphorylation sites of p21 are distributed in the C
      terminal region, we constructed sequential C-terminal truncated fragments and
      examined their ubiquitination in eukaryotic cells. The ubiquitination was
      observed in the 1-164 (full length) and 1-157 fragments with the same efficiency,
      but not in the 1-147 fragment. The lack of ubiquitination in the 1-147 fragment
      was unlikely due to the removal of a Lys residue at position 154, since the p21
      K154R mutant was ubiquitinated as efficiently as the full-length p21.
      Furthermore, the 148-157 deleted form of p21 was not ubiquitinated, just like the
      1-147 fragment. Thus, the C-terminal 148-157 region, not a ubiquitination site by
      itself, should contain an essential regulatory region for the efficient
      ubiquitination of p21.

PMID- 12054573
TI  - Epigenetic control of mouse receptor activator of NF-kappa B ligand gene
      expression.
AB  - Receptor activator of NF-kappa B ligand (RANKL) is a membrane-bound signal
      transducer requisite for differentiation and maintenance of osteoclasts. RANKL
      expression on stromal/osteoblastic cells is tightly regulated to maintain
      physiological serum calcium levels and bone mass. These stromal/osteoblastic
      cells, however, comprise a rather heterogeneous population ranging from immature
      mesenchymal cells to mature osteoblasts and also respond differently to bone
      resorptive stimuli. In the mouse coculture system, we also have demonstrated the
      passage-dependent difference of cultured mouse stromal cells in supporting
      osteoclastogenesis due to altered RANKL gene expression. To address the issue of
      what molecular mechanism gives the diversity of RANKL gene expression to
      stromal/osteoblastic cells, we characterized the mouse RANKL gene promoter that
      contains two CpG clustering regions; one around the transcription start site, and
      the other downstream of the vitamin D response element (VDRE). Using earlier- and
      later-passage mouse ST2 cells, we analyzed the CpG methylation status by sodium
      bisulfite mapping and found that CpG loci around the transcription start site (
      66/+246) were predominantly methylated in later-passage ST2 cells. Moreover,
      earlier- and later-passage ST2 cells transfected with a RANKL promoter construct
      showed the same steady-state level of luciferase activity and of the inducible
      effect of 1,25(OH)(2)D(3). Furthermore, the introduction of methylation to the
      promoter construct silenced promoter activity. The results suggest that CpG
      methylation around the transcription start site of the mouse RANKL gene is an
      important epigenetic event, and that its heterogeneity might cause the diversity
      of the stromal/osteoblastic cells in RANKL gene expression.

PMID- 12054574
TI  - Mechanisms of up-regulation of single calcium channels by serotonin in Helix
      pomatia neurons.
AB  - Action of serotonin (5-HT) on single Ca(2+) channel activity was studied in
      identified neurons of snail Helix pomatia. Only one type of Ca(2+) channels of 5
      pS unitary conductance was determined under patch-clamp cell-attached mode.
      Kinetic analysis have shown a monotonically declining distribution of channel
      open times (OT) with mean time constant of 0.2 ms. The distribution of channel
      closed times (CT) could be fitted by double-exponential curve with time constants
      1 and 12 ms. We established that 5-HT acts on Ca(2+) channel activity indirectly
      via cytoplasm. 5-HT prolonged the OT (up to 0.3 ms) and shortened the CT
      proportionally for both constants to 0.4 and 6 ms correspondingly. A conclusion
      is made that enhancement of Ca(2+) macro-current by 5-HT is determined by kinetic
      changes, increase of the number of active channels, and increase of the
      probability of OT. At the same time the transmitter did not affect the unitary
      channel conductance.

PMID- 12054575
TI  - Degradation of ornithine decarboxylase in Saccharomyces cerevisiae is ubiquitin
      independent.
AB  - Ornithine decarboxylase (ODC), the first rate-limiting enzyme in the polyamine
      biosynthesis is one of the most rapidly degraded proteins in eukaryotic cells.
      Mammalian ODC is a notable exception to the widely accepted dogma that
      ubiquitination is always required for targeting a protein to degradation by the
      26S proteasome. However, while it is well established that in mammalian cells
      degradation of ODC is ubiquitin independent, the requirement of ubiquitination
      for degradation of ODC in yeast cells remained undetermined. We have investigated
      ODC degradation in three mutant strains of Saccharomyces cerevisiae in which
      ubiquitin-dependent protein degradation activity is severely compromised. While
      yeast ODC was rapidly degraded in all these mutant strains the degradation of N
      end rule substrates was inhibited. A mutant mouse ODC that fails to interact with
      Az was rapidly degraded in yeast cells but was stable in mammalian cells
      suggesting that interaction with a mammalian Az like yeast protein is not
      necessary for the degradation of ODC in yeast cells. Deletion analysis revealed
      that sequences from its unique N-terminus are involved in targeting yeast ODC to
      rapid degradation in yeast cells.

PMID- 12054576
TI  - Reduction in cytochrome P-450 enzyme expression is associated with repression of
      CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse
      liver during the acute phase response.
AB  - Expression of P-450 (Cyp) enzymes is reduced in liver during the acute phase
      response, contributing to the decrease in bile acid levels and drug metabolism
      during infection. Nuclear hormone receptors CAR and PXR are key transactivators
      of Cyp2b and Cyp3a genes, respectively. Injection of bacterial lipopolysaccharide
      (LPS) induced the expected reduction in Cyp2b10 and Cyp3a mRNA levels in mouse
      liver. These decreases were associated with a marked reduction in CAR and PXR
      mRNA levels within 4 h following treatment. LPS-induced CAR and PXR repression
      were dose-dependent and sustained for at least 16 h. LPS treatment also reversed
      the up-regulation of Cyp3a in mice pre-treated with PXR ligand RU486. In
      addition, we observed a concomitant decrease in RXR (retinoid X receptor) mRNA
      levels, the obligatory partner of both CAR and PXR for high affinity binding to
      DNA. These findings represent one possible molecular mechanism underlying sepsis
      induced repression of Cyp enzymes.

PMID- 12054577
TI  - Expression of the Musashi1 gene encoding the RNA-binding protein in human
      hepatoma cell lines.
AB  - Musashi1, a neural RNA-binding protein, plays an important role in regulating
      cell differentiation in precursor cells. Recently, expression of Musashi1 has
      been detected in human tumor tissues such as gliomas and melanomas, suggesting
      its involvement in oncogenic development. To determine any association between
      Musashi1 and the development of liver cancer, we investigated its gene expression
      in seven human hepatoma cell lines: HuH6, HuH7, Hep3B, SK-Hep1, HepG2, HLE, and
      HLF. Musashi1 mRNA expression was analyzed using the reverse-transcription
      polymerase chain reaction (PCR), and the PCR products were sequenced using a
      subcloning procedure. Musashi1 protein expression was analyzed in HuH7 and HepG2
      cells by Western blot and immunofluorescence staining. Musashi1 mRNA was detected
      in the HuH6, HuH7, and Hep3B hepatoma cell lines, but not in the others.
      Sequencing of the PCR-amplified Musashi1 cDNA in these three cell lines showed
      the expected sequence of the human Musashi1 gene. Musashi1 protein expression was
      confirmed in HuH7 cells, which were positive for Musashi1 mRNA expression, but
      not in HepG2 cells. These results suggest that Musashi1 expression may be an
      important factor in the development of several types of carcinoma such as human
      hepatoma, and may be a useful molecular marker for tumor detection.

PMID- 12054578
TI  - Characterization of the Mycoplasma hominis ftsZ gene and its sequence variability
      in mycoplasma clinical isolates.
AB  - We cloned and sequenced Mycoplasma hominis chromosomal fragment containing ftsZ
      gene. The wild-type expression of the gene was shown at RNA level by reverse
      transcription followed by PCR amplification. We revealed that M. hominis FtsZ had
      a comparatively low similarity to proteins of Mycoplasma genitalium and
      Mycoplasma pneumoniae. After full ftsZ gene sequencing for 14 clinical isolates
      of M. hominis, single-nucleotide substitutions were found in 21 positions, 6 of
      them being common for almost all isolates. This ftsZ gene polymorphism may be
      used for subtyping of M. hominis in clinical samples. Expression of the M.
      hominis ftsZ gene in different Escherichia coli strains was also demonstrated,
      and M. hominis FtsZ protein was purified from E. coli cells transformed with
      recombinant expression plasmid. Complementation between the M. hominis FtsZ and
      E. coli FtsZ could be shown. The comparison of FtsZ protein structures may also
      be used for investigation of bacterial phylogenetic relationships.

PMID- 12054579
TI  - Characterization of nuclear localization signal in mouse ING1 homolog protein.
AB  - We reported previously that mouse ING1 homolog (mINGh), localized in the nucleus,
      enhanced cell death in HC11 mouse mammary epithelial cells. Analysis of the mINGh
      amino acid sequences revealed the presence of potential nuclear localization
      signal (NLS) and plant homeodomain (PHD) finger DNA binding domain. In the
      present study, NLS site in mINGh was determined using different pieces of mutant
      mINGh proteins, which were fused to green fluorescent protein (GFP), and
      transfected into HC11 cells. NLS of mINGh was split into two parts consisting of
      amino acids KEKK and KKLK. Mutation in NLS sites of mINGh resulted in no
      enhancement of the cell death when over-expressed. These results indicated that
      mINGh contains NLS of bipartite type, which is essential for the regulation of
      cell death.

PMID- 12054580
TI  - Wnt-1 promotes neuronal differentiation and inhibits gliogenesis in P19 cells.
AB  - Wnt-1, the vertebrate counterpart of the Drosophila wingless gene, plays an
      important role in the early morphogenesis of neural tissues. In this report, we
      have shown that overexpression of Wnt-1 can direct embryonic carcinoma P19 cells
      to differentiate into neuron-like cells in the absence of retinoic acid.
      Immunocytochemistry showed that these cells expressed neuronal markers, such as
      the neurofilament (NF) and microtubule-associated protein 2 (MAP2), but failed to
      express the glial cell marker, glial fibrillary acidic protein (GFAP). RT-PCR
      revealed that two basic helix-loop-helix (bHLH) genes, Mash-1 and Ngn-1, were up
      regulated during the differentiation stage of Wnt-1-overexpressing P19 cells.
      These results suggest that the Wnt-1 gene promotes neuronal differentiation and
      inhibits gliogenesis during the neural differentiation of P19 cells, and that
      neural bHLH genes might be involved in this process.

PMID- 12054581
TI  - Mutated focal adhesion kinase induces apoptosis in a human glioma cell line,
      T98G.
AB  - We have established that focal adhesion kinase (FAK)-transfected HL-60 (HL
      60/FAK) cells were highly resistant to hydrogen peroxide and etoposide-induced
      apoptosis compared to vector-transfected cells. Mutagenesis study revealed that
      Y397 is required for anti-apoptotic activity in HL-60/FAK, since Y397F-mutated
      FAK (397FAK) lost anti-apoptotic function. Assuming that 397FAK functions as a
      dominant negative FAK, we introduced 397FAK cDNA into a human glioma cell line,
      T98G, using an adenoviral vector. We found that 397FAK induced marked apoptosis
      with significant FAK degradation. As PI3-kinase-Akt survival pathway was
      constitutively activated in T98G cells, we hypothesized that this pathway was
      shut off by 397FAK gene transfection. As expected, activation of PI3-kinase-Akt
      survival pathway was decreased by the 397FAK gene transfection. 397FAK activated
      mainly caspase-6 which induced degradation of transfected FAK as well as
      endogenous FAK. These results indicated that 397FAK induces apoptosis in T98G
      cells, by interrupting signals of FAK leading to the survival pathway in T98G
      glioma cells.

PMID- 12054582
TI  - Chromosomal organization and localization of the human histone deacetylase 9 gene
      (HDAC9).
AB  - Epigenetically mediated modulation of gene promoter function through histone
      acetylation modifying enzymes, which regulate the acetylation state of histone
      proteins and other promoter-bound transcription factors, is increasingly
      appreciated as a key component in the regulation of reversible gene expression.
      While histone acetyltransferases (HATs), which are frequently part of
      multisubunit coactivator complexes, lead to the relaxation of chromatin structure
      and transcriptional activation, histone deacetylases (HDACs) tend to associate
      with multisubunit corepressor complexes, which result in chromatin condensation
      and transcriptional repression of specific target genes. We have isolated and
      characterized the human HDAC9 genomic sequence, which spans a region of 458 kb
      and which has one single chromosomal locus. Determination of the exon-intron
      splice-junctions established that HDAC9 is encoded by 23 exons ranging in size
      from 22 bp (exon 1) to 264 bp (exon 11). Characterization of the 5' flanking
      genomic region revealed that the human HDAC9 promoter lacks both the canonical
      TATA and CCAAT boxes; CpG elements are missing. The human HDAC9 open reading
      frame is 3036 bp long and encodes a 1011 aa protein with a predictive molecular
      weight of 111.3 kDa and an isoelectric point of 6.41. Fluorescence in situ
      hybridization analysis localized the human HDAC9 gene to chromosome 7p21, a
      region which has been associated particularly with the pathogenesis of
      gynecological tumors.

PMID- 12054583
TI  - Tumor autocrine motility factor induces hyperpermeability of endothelial and
      mesothelial cells leading to accumulation of ascites fluid.
AB  - Accumulation of ascites fluid often observed in some solid tumors is one of the
      most devastating conditions of a patient's difficulty in responding to treatment,
      and to a decrease in the quality of life. Various factors are thought to be
      associated with the formation of cancer-induced fluid accumulation and
      hyperpermeability of a blood vessel is thought to go with this process. Here, we
      report a new factor that is involved in this process, e.g., autocrine motility
      factor (AMF). AMF is a tumor-related cytokine which stimulates the tumor cell
      locomotion and migration and promotes tumor cell invasion during metastasis. AMF
      secretion and its receptor (AMFR) expression in tumor cells are closely
      correlated with disease aggravation of convalescence. The response of endothelial
      or mesothelial cellular morphological alternation to AMF leads to motile
      enhancement and vascular permeability. Tumor AMF induces gaps in an endothelial
      or mesothelial monolayer by stimulating a cellular movement, and accelerates the
      ascites accumulation. And treatment experiment with anti-AMF antibody succeeded
      in the reduction of the ascites accumulation, which renders AMF to the target
      molecule. It is suggested that AMF is one of the significant factors which
      relates to various pathological malignancies induced by tumor mass, and
      understanding of its function could benefit prognosis and treatment.

PMID- 12054584
TI  - Phospholipase D2 stimulates cell protrusion in v-Src-transformed cells.
AB  - Phospholipase D (PLD) activity has been implicated in several aspects of cell
      physiology including vesicle transport, signal transduction, cell proliferation,
      cytoskeletal structure, and oncogenic transformation. Two PLD isoforms (PLD1 and
      PLD2) have been identified and characterized. We have expressed both wild-type
      and catalytically inactive forms of PLD1 and PLD2 in 3Y1 rat fibroblasts and in
      3Y1 cells transformed by v-Src, a tyrosine kinase that elevates PLD activity. The
      v-Src-transformed 3Y1 cells have small, but distinct cell protrusions, implicated
      in cell migration and metastasis. We report here that elevated expression of PLD2
      substantially increased the length of the cell protrusions and that a
      catalytically inactive PLD2 mutant abolished the cell protrusions. The extended
      protrusions in the PLD2-overexpressing cells were dependent upon microtubule
      assembly. These data suggest a role for PLD2 in the v-Src-mediated formation of
      cell protrusions that may be critical for the invasive properties of v-Src
      transformed cells.

PMID- 12054585
TI  - Alloxan is an inhibitor of the enzyme O-linked N-acetylglucosamine transferase.
AB  - We have previously shown that diabetogenic antibiotic streptozotocin (STZ), an
      analog of N-acetylglucosamine (GlcNAc), inhibits the enzyme O-GlcNAc-selective N
      acetyl-beta-d-glucosaminidase (O-GlcNAcase) which is responsible for the removal
      of O-GlcNAc from proteins. Alloxan, another beta-cell toxin is a uracil analog.
      Since the O-GlcNAc transferase (OGT) uses UDP-GlcNAc as a substrate, we
      investigated whether alloxan might interfere with the process of protein O
      glycosylation by blocking OGT, a very abundant enzyme in beta-cells. In isolated
      pancreatic islets, alloxan almost completely blocked both glucosamine-induced and
      STZ-induced protein O-GlcNAcylation, suggesting that alloxan indeed was
      inhibiting (OGT). In order to show definitively that alloxan was inhibiting OGT
      activity, recombinant OGT was incubated with 0-10 mM alloxan, and OGT activity
      was measured directly by quantitating UDP-[(3)H]-GlcNAc incorporation into the
      recombinant protein substrate, nucleoporin p62. Under these conditions, OGT
      activity was completely inhibited by 1 mM alloxan with half-maximal inhibition
      achieved at a concentration of 0.1 mM alloxan. Together, these data demonstrate
      that alloxan is an inhibitor of OGT, and as such, is the first OGT inhibitor
      described.

PMID- 12054586
TI  - Structural analysis of N-glycans from human neutrophil azurocidin.
AB  - N-glycans of human neutrophil azurocidin, enzymatic inactive homolog of serine
      proteinase playing important and multifunctional roles in antimicrobial defense,
      endotoxin binding, monocyte, and T-cell activation, were isolated by
      hydrazinolysis and fluorescence labeled. An ion-exchange chromatography on
      GlycoSep C column separated neutral, mono-, and disialylated glycans. The glycans
      from each group were separated subsequently on GlycoSep N and GlycoSep H columns.
      Sequential exoglycosidase treatment and HPLC mapping allowed determining 21
      different glycan structures, majority of them being neutral (79.8%), the rest
      mono- (13.1%) and disialylated (1.2%).

PMID- 12054587
TI  - Carriers for enzymatic attachment of glycosaminoglycan chains to peptide.
AB  - In the previous study, we have found that the endo-beta-xylosidase from
      Patinopecten had the attachment activities of glycosaminoglycan (GAG) chains to
      peptide. As artificial carrier substrates for this reaction, synthesis of various
      GAG chains having the linkage region tetrasaccharide, GlcA beta 1-3Gal beta 1
      3Gal beta 1-4Xyl, between GAG chain and core protein of proteoglycan was
      investigated. Hyaluronic acid (HA), chondroitin (Ch), chondroitin 4-sulfate
      (Ch4S), chondroitin 6-sulfate (Ch6S), and desulfated dermatan sulfate (desulfated
      DS) as donors and the 4-metylumbelliferone (MU)-labeled hexasaccharide having the
      linkage region tetrasaccharide at its reducing terminals (MU-hexasaccharide) as
      an acceptor were subjected to a transglycosylation reaction of testicular
      hyaluronidase. The products were analyzed by high-performance liquid
      chromatography and enzyme digestion, and the results indicated that HA, Ch, Ch4S,
      Ch6S, and desulfated DS chains elongated by the addition of disaccharide units to
      the nonreducing terminal of MU-hexasaccharide. It was possible to custom
      synthesize various GAG chains having the linkage region tetrasaccharide as
      carrier substrates for enzymatic attachment of GAG chains to peptide.

PMID- 12054589
TI  - Design of novel peptide analogs with potent fungicidal activity, based on PMAP-23
      antimicrobial peptide isolated from porcine myeloid.
AB  - PMAP-23 is a 23-mer peptide derived from porcine myeloid. To develop novel
      antifungal peptides useful as therapeutic drugs, it would require a strong
      fungicidal activity against pathogenic fungal cells. To this goal, several
      analogs, with amino acid substitutions, were designed to increase the net
      hydrophobicity by Trp (W)-substitution at positions 10, 13, or 14 at the
      hydrophilic face of PMAP-23 without changing the hydrophobic helical face. The
      Trp (W)-substitution (P6) showed an enhanced fungicidal and antitumor activities,
      with the fungicidal activity inhibited by salts and the respiratory inhibitor,
      NaN(3). The results suggested that the increase of hydrophobicity of the peptides
      correlated with fungicidal activity. The fungicidal effects of analog peptides
      were further investigated using 1,6-diphenyl-1,3,5-hexatriene (DPH) as a membrane
      probe. In Candida albicans, the analog peptide (P6) exerted its fungicidal effect
      on the blastoconidia in 20% fetal bovine serum by disrupting the mycelial forms.
      Furthermore, P6 caused significant morphological changes, and these facts
      suggested that the fungicidal function of the novel analog peptide (P6) was by
      damaging the fungal cell membranes. Thus, this peptide may provide a useful
      template for designing novel antifungal peptides useful for the treatment of
      infectious diseases.

PMID- 12054588
TI  - Isolation of Chinese hamster ovary cell pex mutants: two PEX7-defective mutants.
AB  - We searched for novel Chinese hamster ovary (CHO) cell mutants defective in
      peroxisome biogenesis by an improved method using peroxisome targeting signal 2
      (PTS2)-tagged enhanced green fluorescent protein (EGFP). From mutagenized TKaEG2
      cells, the wild-type CHO-K1 stably expressing rat Pex2p and PTS2-EGFP, cell
      colonies resistant to the 9-(1(')-pyrene)nonanol/ultraviolet treatment were
      examined for intracellular location of PTS2-EGFP. Of six mutant cell clones two,
      ZPEG227 and ZPEG231, showed cytosolic PTS2-EGFP, indicative of impaired PTS2
      import, and numerous PTS1-positive particles. PEX7 expression restored the
      impaired PTS2 import in both mutants. Cell fusion with fibroblasts from a patient
      with PEX7-defective rhizomelic chondrodysplasia punctata did not complement PTS2
      import defect of ZPEG227 and ZPEG231, confirming that these two are pex7 mutants.
      Mutation analysis of PEX7 by reverse transriptase (RT)-PCR indicated that ZPEG227
      allele carried an inactivating nonsense mutation, Trp158Ter. Therefore, ZPEG227
      is a pex7 mutant possessing a newly identified mutation in mammalian pex7 cell
      lines.

PMID- 12054590
TI  - Specific packaging of spliced retroviral vector transcripts lacking the Psi
      region.
AB  - The effect of a cryptic splice acceptor (cSA) site located at the end of the
      extended packaging signal in murine leukemia virus (MLV)-based vectors was
      investigated. Although this cSA is also present in wild type MLV, it was found to
      result in a smaller transcript in which the packaging signal (Psi) had been
      removed by splicing only in MLV-derived vectors. Splicing occurs both in
      packaging cells producing the MLV-vectors as well as in the infected target
      cells. Transcripts lacking the Psi-sequence (Psi(-)) are packaged relatively
      efficiently into virus particles, even in the presence of wild type Psi(+)-vector
      transcripts. The Psi(-)-viral RNA is reverse transcribed in vector transduced
      cells as is any other retroviral genome. The titer obtained from the Psi(-)
      vector was only 1000-fold reduced in comparison to the same Psi(+)-vector. These
      results suggest that Psi(-)-transcripts may be packaged more frequently than
      previously supposed and that splicing patterns should be carefully analysed on an
      individual basis for retroviral vectors used in gene therapy.

PMID- 12054591
TI  - A missense mutant myostatin causes hyperplasia without hypertrophy in the mouse
      muscle.
AB  - Myostatin, which is a member of the TGF-beta superfamily, is a negative regulator
      of skeletal muscle formation. Double-muscled Piedmontese cattle have a C313Y
      mutation in myostatin and show increased skeletal muscle mass which resulted from
      an increase of myofiber number (hyperplasia) without that of myofiber size
      (hypertrophy). To examine whether this mutation in myostatin gene affects muscle
      development in a dominant negative manner, we generated transgenic mice
      overexpressing the mutated gene. The transgenic mice exhibited dramatic increases
      in the skeletal muscle mass resulting from hyperplasia without hypertrophy. In
      contrast, it has been reported that a myostatin mutated at its cleavage site
      produces hypertrophy without hyperplasia in the muscle. Thus, these results
      suggest that (1) the myostatin containing the missense mutation exhibits a
      dominant negative activity and that (2) there are two types in the dominant
      negative form of myostatin, causing either hypertrophy or hyperplasia.

PMID- 12054592
TI  - Nuclear factor (NF)-kappa B blockade attenuates but does not abrogate LPS
      mediated interleukin (IL)-1 beta biosynthesis in alveolar epithelial cells.
AB  - The role that the nuclear factor (NF)-kappa B plays in regulating the
      biosynthesis of interleukin (IL)-1 beta, an inflammatory cytokine, has been
      investigated in vitro. Irreversible inhibition of the proteasome complex by
      carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 microM) had no inhibitory
      effect on lipopolysaccharide (LPS)-mediated IL-1 beta biosynthesis. Furthermore,
      selective inhibition of NF-kappa B by the action of caffeic acid phenylethyl
      ester (CAPE; 1-100 microM) and sulfasalazine (SSA; 0.1-10 mM), a potent and
      irreversible inhibitor of NF-kappa B, partially attenuated but did not abolish
      LPS-dependent IL-1 beta secretion. Incorporation of a selectively permeant
      inhibitor of NF-kappa B, SN-50 (1-20 microM), a peptide which contains the
      nuclear localization sequence (NLS) for the p50 NF-kappa B subunit and the amino
      terminal sequence of Kaposi fibroblast growth factor to promote cell
      permeability, attenuated in a dose-dependent manner LPS-mediated release of IL-1
      beta. It is concluded that the NF-kapp B pathway is partially implicated and its
      blockade attenuates but does not abrogate LPS-dependent IL-1 beta biosynthesis in
      alveolar epithelial cells.

PMID- 12054593
TI  - 5'-Nucleotidases: specific assays for five different enzymes in cell extracts.
AB  - Several mammalian 5'-nucleotidases (5-NTs), attached to membranes or present in
      the cytosol or in mitochondria, remove the phosphate from ribo- and
      deoxyribonucleotides with different specificities for the sugar and base
      moieties. Some enzymes probably participate in signaling functions by producing
      adenosine from AMP. A more general function may be to prevent overproduction of
      deoxyribonucleotides. 5-NTs may affect the pharmacological activity of nucleoside
      analogs and also be involved in their mitochondrial toxicity. Here we describe
      for five cloned 5-NT specific assays that largely rely on new inhibitors for some
      of the enzymes. The assays can be used to quantitate each enzyme in crude cell
      extracts. To ascertain their validity we applied each assay to extracts from
      genetically modified cells that overproduce separately each of the five enzymes.
      The methodology should be useful in further studies of the physiological function
      of 5-NTs and their influence on the clinical use of nucleoside analogs.

PMID- 12054594
TI  - Unique capping activity of the recombinant RNA polymerase (L) of vesicular
      stomatitis virus: association of cellular capping enzyme with the L protein.
AB  - Vesicular stomatitis virus (VSV), a prototype of non-segmented negative strand
      RNA viruses, packages an RNA-dependent RNA polymerase (L) which, together with an
      associated phosphoprotein (P), transcribes the genome RNA, in vitro and in vivo,
      into mRNAs that are capped at the 5'-ends. However, unlike cellular
      guanlylyltransferase (GT), the RNA polymerase incorporates GDP in the capped
      structure, as Gp(alpha)p(beta)-p(alpha)A. In an effort to characterize the
      capping activity of the RNA polymerase, we have purified recombinant L (rL)
      protein expressed in insect cells. The rL, like the virion L polymerase, also
      caps transcribed mRNAs with identical unique cap structure. Interestingly, the
      purified rL is found to be tightly bound to the GT of the insect cell during all
      stages of purification. VSV grown in baby hamster kidney cells also packages
      cellular GT of the murine cell, suggesting that VSV L protein or its associated
      proteins may have a strong affinity for the cellular GT. The GT bound to rL,
      however, formed E-GMP complex, whereas no such complex was detected with the rL
      protein. It appears that the L protein may contain the putative active site for
      the unique capping reaction or the tightly bound cellular GT may by some unknown
      mechanism participate in the unique capping reaction.

PMID- 12054595
TI  - Identification of the peroxisomal beta-oxidation enzymes involved in the
      degradation of leukotrienes.
AB  - Leukotrienes (LTs) are metabolically inactivated via omega-oxidation and
      subsequent beta-oxidation from the omega-end. This beta-oxidation process takes
      place in peroxisomes. In this study we investigated the role of different enzymes
      involved in peroxisomal beta-oxidation in the degradation of LTs. We analyzed
      LTB(4), LTE(4), and their oxidation products in urine of patients with Infantile
      Refsum's disease (IRD), d-bifunctional protein (DBP) deficiency, Rhizomelic
      Chondrodysplasia Punctata (RCDP) type 1, and X-linked adrenoleukodystrophy
      (XALD). We found that patients with IRD and DBP deficiencies excrete increased
      amounts of LTB(4), LTE(4), omega-carboxy-LTB(4), and omega-carboxy-LTE(4) in
      their urine, whereas the beta-oxidation products were not detectable. These
      results show that DBP plays an essential role in the degradation of LTs. In urine
      of patients with XALD and RCDP type 1 we found normal levels of LTB(4), LTE(4),
      and their oxidation products, indicating that the adrenoleukodystrophy protein
      and peroxisomal 3-ketoacyl-CoA thiolase are not involved in the metabolic
      inactivation of LTs.

PMID- 12054596
TI  - Genetic analysis of four novel peroxisome proliferator activated receptor-gamma
      splice variants in monkey macrophages.
AB  - Peroxisome proliferator activated receptor-gamma (PPAR-gamma) is abundantly
      expressed in atherosclerotic lesions and is implicated in atherogenesis. The
      existence of three splice variants, PPAR-gamma 1, PPAR-gamma 2, and PPAR-gamma 3
      has been established. Using monocyte-derived macrophages from cynomolgus monkeys,
      we demonstrate here the identification of two new PPAR-gamma exons, exon C and
      exon D, which splice together with already established exons A1, A2, and B in the
      5(') terminal region to generate four novel PPAR-gamma subtypes, PPAR-gamma 4, 
      gamma 5, -gamma 6, and -gamma 7. PPAR-gamma 4 and gamma 5 were detected only in
      macrophages whereas gamma 6 and gamma 7 were expressed both in macrophages and
      adipose tissues. None of these novel isoforms were detected in muscle, kidney,
      and spleen from monkeys. We found sequences identical to exons C and D in the
      human genome database. These and all PPAR-gamma exons known to date are encoded
      by a single gene, located from region 10498 K to 10384 K on human chromosome 3.
      We cloned and expressed PPAR-gamma 1, PPAR-gamma 4, and PPAR-gamma 5 proteins in
      yeast using the expression vector pPICZB. As expected, all recombinant proteins
      showed a molecular weight of approximately 50 kDa. We also investigated the
      effect of a high-fat diet on the level of macrophage PPAR-gamma expression in
      monkeys. RT-PCR showed a significant increase in total PPAR-gamma and ABCA1 mRNA
      levels in macrophages of fat-fed monkeys (n=7) compared to those maintained on a
      normal diet (n=2). However, none of the novel isoforms seemed to be induced by
      fat-feeding. We used tetracycline-responsive expression vectors to obtain
      moderate expression of PPAR-gamma 4 and -gamma 5 in CHO cells. In these cells,
      expression of PPAR-gamma 5 but not -gamma 4 repressed the expression of ABCA1.
      Neither isoform modulated the expression of lipoprotein lipase. Our results
      suggest that individual PPAR-gamma isoforms may be responsible for unique tissue
      specific biological effects and that PPAR-gamma 4 and -gamma 5 may modulate
      macrophage function and atherogenesis.

PMID- 12054597
TI  - Molecular analysis of expansion, differentiation, and growth factor treatment of
      human chondrocytes identifies differentiation markers and growth-related genes.
AB  - This study is intended to optimise expansion and differentiation of cultured
      human chondrocytes by growth factor application and to identify molecular markers
      to monitor their differentiation state. We dissected the molecular consequences
      of matrix release, monolayer, and 3D-alginate culture, growth factor optimised
      expansion, and re-differentiation protocols by gene expression analysis. Among 19
      common cartilage molecules assessed by cDNA array, six proved best to monitor
      differentiation. Instant down-regulation at release of cells from the matrix was
      strongest for COL 2A1, fibromodulin, and PRELP while LUM, CHI3L1, and CHI3L2 were
      expansion-related. Both gene sets reflected the physiologic effects of the most
      potent growth-inducing (PDGF-BB) and proteoglycan-inducing (BMP-4) factors. Only
      CRTAC1 expression correlated with 2D/3D switches while the molecular phenotype of
      native chondrocytes was not restored. The markers and optimised protocols we
      suggest can help to improve cell therapy of cartilage defects and chondrocyte
      differentiation from stem cell sources.

PMID- 12054598
TI  - Overexpression of VDUP1 mRNA sensitizes HeLa cells to paraquat.
AB  - 5-Bromodeoxyuridine (BrdU) induces or suppresses senescence-associated genes in
      any types of mammalian cells. From a cDNA library upregulated by BrdU in HeLa
      cells, we identified the gene encoding VDUP1 as a senescence-associated gene in
      normal human fibroblasts. To address a role of VDUP1 in senescence, we
      established HeLa cell clones, V7 and V27, which express its mRNA in a doxycycline
      dependent manner. Although their growth in liquid culture was moderately
      retarded, colony formation on semi-solid medium was strongly inhibited by
      overexpression of the mRNA. We also examined susceptibility of these clones to
      various reagents. Consequently, colony formation in liquid culture was strongly
      inhibited by paraquat in these clones. Their superoxide dismutase activity was
      normal.

PMID- 12054599
TI  - Restoration of p53 tumor suppressor pathway in human cervical carcinoma cells by
      sodium arsenite.
AB  - In most cervical cancer cells, p53 and Rb are disrupted by human papillomaviruses
      (HPVs) E6 and E7, respectively. Restoration of p53 or Rb function by blocking
      E6/p53 or E7/Rb pathway might be a potential therapeutic purpose for these cancer
      cells. Treatment with sodium arsenite (SA) resulted in significant repression of
      E6 and E7 mRNA levels in SiHa cells. After E6 and E7 repression, p53 was
      dramatically induced and accumulated in cellular nuclei and Rb was also induced.
      Two p53-responsive genes, p21(waf1/cip1) and mdm2, were induced after SA
      treatment. Furthermore, SA also reduced the expressions of Cdc25A and cyclin B,
      blocked cell cycle progression at G2/M phase, and induced apoptosis in SiHa
      cells. SA-induced apoptosis was greatly reduced by expression of a dominant
      negative mutated p53. In this study, we have first demonstrated that SA did
      repress E6 and E7 oncogenes, restore the p53 tumor suppressor pathway and induce
      apoptosis in SiHa cells. Therefore, it would be a potential strategy to promote
      SA as therapeutic purpose for HPV-positive cancer cells.

PMID- 12054600
TI  - Enhanced SUMOylation in polyglutamine diseases.
AB  - Small ubiquitin-like modifiers (SUMOs) are proteins homologous to ubiquitin that
      possibly regulate intranuclear protein localization, nuclear transport, and
      ubiquitination. We examined patients of DRPLA, SCA1, MJD, and Huntington's
      disease and found that neurons in affected regions of the brain react strongly to
      SUMO-1, a family member of SUMOs. Western blot with a transgenic mouse expressing
      mutant ataxin-1 showed the increase of SUMOylated proteins in the cerebellar
      cortex, which we named ESCA1 and ESCA2. These results indicated activation of
      SUMO-1 system in polyglutamine diseases and predicted its involvement in the
      pathology.

PMID- 12054601
TI  - Lipid kinases and Ca(2+) signaling in Trypanosoma cruzi stimulated by a synthetic
      peptide.
AB  - The synthetic peptide carrying residues 1-40 of chicken alpha(D)-globin, which
      promotes differentiation in Trypanosoma cruzi epimastigote, stimulated PPtdIns-k,
      DAG-k, and PA-k activities in a dose-dependent manner. A biphasic behavior only
      for PPtdIns-k and DAG-k was demonstrated by changes in [(32)P]PPtdIns and PtdOH
      levels, the earlier phase peaking at 3 min with a return to basal levels by 6 min
      and then a second phase with a sustained increase in time. This behavior was not
      observed for PA-k; the DGPP levels peaked at 6 min and were sustained in time.
      PMA pretreatment only abolished the first peak of PPtdIns-k, DAG-k activities,
      and InsPs/InsP(3) levels. There was also a transient elevation in intracellular
      calcium concentration, but this variation was modified only 50% by PMA. The
      results suggest that peptide 1-40 induces activation of the inositol cycle
      through lipid kinase activation in a biphasic manner. In this response, the early
      increase of enzymatic activities would be regulated by PKC and the InsP(3) may
      only be responsible, in part, for the calcium signaling.

PMID- 12054602
TI  - Probing the membrane topology of a subunit of the mitochondrial protein
      translocase, Tim44, with biotin maleimide.
AB  - Tim44 is an essential component of the translocase of the inner mitochondrial
      membrane (TIM) complex that mediates transport of nuclear encoded mitochondrial
      precursors across the inner membrane. Here, we have investigated the topology of
      Tim44 by probing mitochondria with membrane impermeable 3-(N
      maleimidopropionyl)biocytin (MPB) followed by the specific immunoprecipitation of
      modified proteins. Our data indicate that a single cysteine residue, Cys-369,
      located in the C-terminal domain of the yeast Tim44 is exposed to the
      mitochondrial intermembrane space.

PMID- 12054603
TI  - Conserved physical linkage of GnRH-R and RBM8 in the medaka and human genomes.
AB  - Candidate genes for human type II gonadotropin-releasing hormone receptor (GnRH
      RII) reside on two separate loci, 1q12-q21 and 14q21-23, yet neither locus
      generates functional GnRH-RII. Instead, their opposite DNA strands encode
      functional RNA-binding motif protein 8 (RBM8s), which is also encoded by another
      locus, 5q13-q14. To elucidate the mechanism through which such multiple human
      GnRH-RII/RBM8 loci arose, here we have defined an RBM8 locus in a comparative
      model species, the medaka Oryzias latipes. The medaka RBM8, which exists as a
      single copy gene, is linked to, but does not overlap with, GnRH-R2 on linkage
      group (LG) 16, demonstrating the ancient origin of the physical linkage between
      GnRH-R and RBM8. The medaka LG 16 contains orthologous segments to the human
      chromosome 1 and therefore the 1q12-q21 locus would be an originating human GnRH
      RII/RBM8 segment. Furthermore, like the human RBM8s on 1q12-q21 and 5q13-q14 but
      not that on 14q21-q23, the medaka RBM8 is a multiexon gene, indicating that the
      14q21-q23 and 5q13-q14 loci were generated by retrotransposition and segmental
      genomic duplication, respectively, of the originating 1q12-q21 locus.

PMID- 12054605
TI  - LXR alpha is the dominant regulator of CYP7A1 transcription.
AB  - Cholesterol 7 alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the
      classic pathway of bile acid biosynthesis. Dietary cholesterol stimulates CYP7A1
      transcription via activation of oxysterol receptor, LXR alpha, whereas bile acids
      repress transcription through FXR-mediated induction of SHP protein. The aim of
      this study was to determine the quantitative role that LXR- and FXR-regulated
      pathways play in regulating CYP7A1 and SHP in both rat and hamster models. In
      rats fed a 2% cholesterol diet, both SHP and CYP7A1 mRNA levels were elevated.
      The inability to induce CYP7A1 mRNA levels by cholesterol feeding in hamsters led
      to a decline in SHP mRNA levels. Elimination of hepatic bile acid flux by
      cholestyramine or bile fistula resulted in a marked repression of rat SHP mRNA
      levels. These results suggest that under conditions of both SHP and LXR alpha
      activation, stimulatory effect of LXR alpha overrides the inhibitory effect of
      FXR and results in an induction of rat CYP7A1 mRNA levels.

PMID- 12054604
TI  - Regulation of angiogenesis by the aging suppressor gene klotho.
AB  - Advanced age is a major risk factor of peripheral artery disease. We examined the
      effects of the aging-suppressor gene klotho on angiogenesis in response to
      ischemia by introducing ischemic hindlimb model in mice heterozygously deficient
      for the klotho gene and in wild type mice. Blood flow recovery as assessed by
      laser doppler perfusion imaging and angiogenesis as assessed by density of PECAM
      1/CD31-positive positive capillaries were markedly impaired in mice
      heterozygously deficient for the klotho gene (both <0.05). Our findings show that
      the aging-suppressor gene klotho affects angiogenesis and the possibility that
      age-related impairment of angiogenesis might be regulated by the klotho gene. Our
      results present a new possibility of therapeutic angiogenesis for patients of
      advanced age.

PMID- 12054606
TI  - Plasmid DNA activates murine macrophages to induce inflammatory cytokines in a
      CpG motif-independent manner by complex formation with cationic liposomes.
AB  - Plasmid DNA (pDNA) is very important in non-viral gene therapy and DNA
      vaccination. Unmethylated CpG motifs in bacterial DNA, but not in vertebrate DNA,
      are known to trigger an inflammatory response, which inhibits gene expression
      while improving immunological consequences. In this report, we investigated the
      cytokine secretion induced by pDNA/cationic liposome complexes using murine
      macrophages. Naked CpG DNA induced tumor necrosis factor-alpha (TNF-alpha)
      secretion from the macrophages, but DNA without CpG motif did not, demonstrating
      that the cytokine induction was mediated by CpG motifs. pDNA complexed with
      cationic liposomes, but not the cationic liposomes alone, produced a significant
      amount of TNF-alpha from the macrophages. Surprisingly, methylated pDNA and calf
      thymus DNA complexed with the cationic liposomes were also able to induce TNF
      alpha production, indicating that these responses were not dependent on CpG
      motifs. Taken together, the present study demonstrated that for the first time
      DNA can stimulate murine macrophages in a CpG motif-independent manner when it is
      complexed with the cationic liposomes.

PMID- 12054607
TI  - Lethal toxin of Bacillus anthracis causes apoptosis of macrophages.
AB  - Lethal toxin is a major anthrax virulence factor, causing the rapid death of
      experimental animals. Lethal toxin can enter most cell types, but only certain
      macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have
      shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger
      intracellular signaling events typical for apoptosis, including changes in
      membrane permeability, loss of mitochondrial membrane potential, and DNA
      fragmentation. The cells were protected from the toxin by specific inhibitors of
      caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was
      inhibited by sublytic concentrations of lethal toxin. Infection of cells with
      anthrax (Sterne) spores impaired their bactericidal capacity, which could be
      reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather
      than direct lysis is biologically relevant to lethal toxin intracellular
      activity.

PMID- 12054608
TI  - Identification and characterization of C6orf37, a novel candidate human retinal
      disease gene on chromosome 6q14.
AB  - We have identified a novel human gene, chromosome 6 open reading frame 37
      (C6orf37), that is expressed in the retina and maps to human chromosome 6q14, a
      genomic region that harbors multiple retinal disease loci. The cDNA sequence
      contains an open reading frame of 1314 bp that encodes a 437-amino acid protein
      with a predicted molecular mass of 49.2 kDa. Northern blot analysis indicates
      that this gene is widely expressed, with preferential expression observed in the
      retina compared to other ocular tissues. The C6orf37 protein shares homology with
      putative proteins in R. norvegicus, M. musculus, D. melanogaster, and C. elegans,
      suggesting evolutionary conservation of function. Additional sequence analysis
      predicts that the C6orf37 gene product is a soluble, globular cytoplasmic protein
      containing several conserved phosphorylation sites. Furthermore, we have defined
      the genomic structure of this gene, which will enable its analysis as a candidate
      gene for chromosome 6q-associated inherited retinal disorders.

PMID- 12054609
TI  - Autoinduction of the trefoil factor 2 (TFF2) promoter requires an upstream cis
      acting element.
AB  - Trefoil factor 2 (TFF2)/spasmolytic polypeptide (SP) is a highly stable peptide
      which is abundantly expressed and secreted by mucous cells of the stomach and
      which functions in gastric cytoprotection. Previous studies from our group have
      shown that TFF2 is an immediate early gene capable of regulating its own
      expression through activation of the TFF2 promoter. We therefore aimed to
      investigate the cis-acting elements mediating this response in AGS cells
      transfected with TFF2 promoter-reporter gene constructs, using a TFF2-expression
      system resembling physiologic paracrine conditions. TFF2 peptide expression was
      achieved through stable transfection of AGS cells with a TFF2-expression
      construct. Stimulation of transiently transfected cells with this TFF2-containing
      conditioned media resulted in a significant increase in TFF2 promoter activity.
      Promoter stimulation was blocked by an anti-TFF2 antibody, indicating that it was
      mediated specifically by TFF2. Deletion analysis of the TFF2 promoter led to the
      identification of a specific response element located between -191 and -174
      upstream of the transcriptional initiation site. This region of the promoter,
      which was designated SPRE (for spasmolytic polypeptide response element), was
      sufficient to confer responsiveness in a heterologous promoter system. Mutational
      analysis and electrophoretic mobility shift assays (EMSA) showed that a GAG motif
      was responsible for mediating promoter activation in response to TFF2
      stimulation. Since auto- and cross-induction of TFF2 promoter is likely to be a
      means of rapid amplification of TFF2 expression in the critical first minutes
      following mucosal injury, these results should lead to insight into the molecular
      events initiating epithelial restitution and healing.

PMID- 12054610
TI  - Rab7 gene is up-regulated by cholesterol-rich diet in the liver and artery.
AB  - To identify genes responding to the cholesterol-rich diet, differentially
      expressed hepatic genes have been searched from a diet-induced
      hypercholesterolemic rabbit by differential display reverse transcription
      polymerase chain reaction (DDRT-PCR). Among the many screened genes, Rab7 gene
      was shown to be distinctively up-regulated in response to the cholesterol-loading
      into the rabbit. To visualize the location of elevated Rab7 expression in
      tissues, patterns of the gene expression were monitored within hepatic and aortic
      tissues by in situ hybridization and immunohistochemistry. The expression of Rab7
      was obviously increased in the hepatic tissues, especially in the endothelial
      cells and hepatocytes around central veins of the high cholesterol-fed rabbit,
      compared to the tissues from rabbit fed a normal diet. To find out a potential
      relationship between the Rab7 and the atherogenesis, the same experiments were
      conducted with the atherosclerotic plaques obtained from rabbit and human. The
      elevated expression of Rab7 gene was clearly evident in both tissues, suggesting
      that the Rab7 may be involved in the process of atherogenesis.

PMID- 12054611
TI  - Modulation of intracellular Ca(2+) via alpha(1B)-adrenoreceptor signaling
      molecules, G alpha(h) (transglutaminase II) and phospholipase C-delta 1.
AB  - We characterized the alpha(1B)-adrenoreceptor (alpha(1B)-AR)-mediated
      intracellular Ca(2+) signaling involving G alpha(h) (transglutaminase II, TGII)
      and phospholipase C (PLC)-delta 1 using DDT1-MF2 cell. Expression of wild-type
      TGII and a TGII mutant lacking transglutaminase activity resulted in significant
      increases in a rapid peak and a sustained level of intracellular Ca(2+)
      concentration ([Ca(2+)](i)) in response to activation of the alpha(1B)-AR.
      Expression of a TGII mutant lacking the interaction with the receptor or PLC
      delta 1 substantially reduced both the peak and sustained levels of [Ca(2+)](i).
      Expression of TGII mutants lacking the interaction with PLC-delta 1 resulted in a
      reduced capacitative Ca(2+) entry. Reduced expression of PLC-delta 1 displayed a
      transient elevation of [Ca(2+)](i) and a reduction in capacitative Ca(2+) entry.
      Expression of the C2-domain of PLC-delta 1, which contains the TGII interaction
      site, resulted in reduction of the alpha(1B)-AR-evoked peak increase in
      [Ca(2+)](i), while the sustained elevation in [Ca(2+)](i) and capacitative Ca(2+)
      entry remained unchanged. These findings demonstrate that stimulation of PLC
      delta 1 via coupling of the alpha(1B)-AR with TGII evokes both Ca(2+) release and
      capacitative Ca(2+) entry and that capacitative Ca(2+) entry is mediated by the
      interaction of TGII with PLC-delta 1.

PMID- 12054612
TI  - Differential display of expressed genes in pancreatic cancer cells.
AB  - Activating K-ras mutations occur in 80-95% of pancreatic cancers. The purpose of
      this study was to conduct an open, panoramic survey of gene expression, using K
      ras status as the axis over which to sub-classify pancreatic cancers.
      Differential display was used to contrast mRNA purified from exponentially
      growing PANC-1 and Capan-2 cells (mutated K-ras) with Hs766T and BxPC-3 cells
      (wild-type). Differences were confirmed by Northern analysis. Twenty-five
      transcripts were differentially expressed by a factor of two or more. Four
      transcripts were over-expressed and twelve were under-expressed in the mutants
      relative to the wild-types. The transcripts most strikingly over-expressed by the
      mutant cell lines were MARCKS, DKFZp547C244, and RPLP2. The transcripts over
      expressed by the wild-types were CEACAM6, cDNA AK026924, and myosin light chain
      6. Profiling of gene expression with respect to K-ras mutation status may lead to
      new insights into pancreatic cancer pathogenesis, as well as to the
      identification of novel therapeutic targets.

PMID- 12054613
TI  - Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two
      orphan G-protein-coupled receptors.
AB  - Endocrine gland-derived vascular endothelial growth factor (EG-VEGF, identical to
      prokineticin 1) is a novel peptide recently identified as a selective mitogen for
      endocrine gland endothelial cells. The present study demonstrates that EG
      VEGF/prokineticin 1 and a peptide closely related to EG-VEGF, prokineticin 2, are
      cognate ligands of two orphan G-protein-coupled receptors designated ZAQ (=EG
      VEGF/PK-R1) and I5E (=EG-VEGF/PK-R2). EG-VEGF/prokineticin 1 and prokineticin 2
      induced a transient increase in intracellular calcium ion concentration
      ([Ca(2+)](i)) with nanomolar potency in Chinese hamster ovary (CHO) cells
      expressing EG-VEGF/PK-R1 and -R2 and bind to these cells with high affinity and
      with different receptor selectivity. EG-VEGF/prokineticins provoke rapid
      phosphorylation of p44/42 MAP kinase and DNA synthesis in the bovine adrenal
      capillary endothelial cells (BACE). The mRNAs of both EG-VEGF/PK-R1 and -R2 were
      expressed in BACE. The identification of the receptors for EG-VEGF/prokineticins
      may provide a novel molecular basis for the regulation of angiogenesis in
      endocrine glands.

PMID- 12054615
TI  - Induction of pro-renin converting enzyme mk9 by thyroid hormone in the guinea-pig
      liver.
AB  - Kallikreins are a group of specific serine proteases and are an integral part of
      kallikrein-kinin system. The kallikrein-kinin system is hypotensive in nature and
      counteracts with the renin-angiotensin system in the maintenance of normal blood
      pressure. So far, four kallikrein-like enzymes, namely, mK9, mK13, mK22, and
      mK26, have been known to convert the inactive pro-renin into biologically active
      renin. Some of these enzymes are induced by the thyroid hormone. In the proposed
      study, we investigated the effects of thyroid hormone on the expression of genes
      for mk9, mk13, and mk22 enzymes. We used guinea pigs as models because these
      animals share many characteristics in common to humans. Male adult guinea pigs
      were intramuscularly injected with 2 mg/kg body weight of thyronine. Forty-eight
      hours following the last injection, the liver was processed for Northern blot
      analysis using labeled mK9, mK13, and mK22 specific RNA probes. Only mK9 was
      found to be transcriptionally regulated by the hormone.

PMID- 12054614
TI  - Evidence of two forms of poly(A) polymerase in germinated wheat embryos and their
      regulation by a novel protein kinase.
AB  - Two forms of poly(A) polymerase (PAPI and PAPII) from germinated wheat embryos
      have been resolved on DEAE-cellulose ion-exchange chromatography by a linear
      gradient of 0-500 mM (NH(4))(2)SO(4). Further purification shows that both forms
      are monomeric in nature with an identical molecular weight, approximately 65 kDa.
      The phosphoprotein nature of PAPI and PAPII has been established by in vivo
      labelling with (32)P-orthophosphate. Acid hydrolysis of both (32)P-labelled
      purified PAPI and PAPII has revealed that phosphorylations generally take place
      in serine and threonine residues. PAPI and PAPII have also been characterised
      with respect to V(max) and K(m) for poly(A). The V(max) and K(m) values of PAPI
      are 28.57 and 11.37 microg, respectively, whereas 34.48 and 7.04 microg of PAPII.
      In vitro dephosphorylation of the purified enzyme by alkaline phosphatase leads
      to a significant loss of the enzyme activity, which is regained upon
      phosphorylation by a 65 kDa protein kinase (PK) purified from wheat embryos. The
      extent of phosphorylation by protein kinase shows that PK has similar affinity
      towards both PAPI and PAPII, whereas the phosphate incorporation in PAPII is
      twofold higher than PAPI suggesting their distinct chemical nature.

PMID- 12054616
TI  - Effects of polyhydroxy compounds on the structure and activity of alpha
      chymotrypsin.
AB  - The effects of glycerol, polyethylene glycol, fructose, glucose, sorbitol, and
      saccharose on the conformation and catalytic activity of alpha-chymotrypsin were
      studied in 0.1 M sodium phosphate buffer and buffered aqueous 60% ethanol (pH
      8.0). The enzyme activity was practically completely lost within 10 min in 60%
      ethanol, but in the presence of stabilizers the activity was retained. With the
      exception of polyethylene glycol, the stabilizing effect decreased with increase
      of the incubation time. The preservation of the catalytic activity was
      accompanied by changes in the secondary and tertiary structures of alpha
      chymotrypsin.

PMID- 12054617
TI  - Molecular isolation and characterization of novel four subisoforms of ECE-2.
AB  - Endothelin-converting enzymes (ECEs) are the key enzymes in the endothelin (ET)
      biosynthesis that catalyze the conversion of big ET, the biologically inactive
      precursor of mature ET. Two enzymes, termed ECE-1 and ECE-2, have been
      molecularly identified. Here, we report novel four subisoforms of ECE-2 that
      differ in their N-terminal cytoplasmic tails, termed ECE-2a-1, ECE-2a-2, ECE-2b
      1, and ECE-2b-2. RT-PCR analysis of these subisoforms in bovine tissues
      demonstrated that their tissue distribution was strikingly different. ECE-2a-1
      and ECE-2a-2 are expressed in a variety of tissues including liver, kidney,
      adrenal gland, testis, and endothelial cells, while ECE-2b-1 and ECE-2b-2 are
      expressed abundantly in brain and adrenal gland. Furthermore, ECE-2a-1 and ECE-2b
      2 were revealed to be predominant forms as compared to ECE-2a-2 and ECE-2b-1,
      respectively. Immunohistochemical analyses of CHO cells, stably expressing ECE-2a
      1 or ECE-2b-2, revealed that both ECE-2a-1 and ECE-2b-2 were localized in
      intracellular compartments but not on the cell surface. Detailed analysis of ECE
      2 subisoforms will provide crucial information to clarify the physiological
      function of ECE-2.

PMID- 12054618
TI  - A novel protocol based on HN(C)N for rapid resonance assignment in ((15)N, (13)C)
      labeled proteins: implications to structural genomics.
AB  - A novel protocol, based on the HN(C)N experiment, has been developed for rapid
      assignment of backbone H(N) and (15)N resonances in ((15)N, (13)C) labeled
      proteins. The protocol exploits the directly observable (15)N and H(N) sequential
      correlations and the distinctive peak patterns in the different planes of the
      HN(C)N spectrum, depending upon the nature of the residues displaying the
      correlations. Glycines and prolines, which are responsible for the distinctive
      features, provide many check/start points for the sequential walks. These
      features enhance the speed of data analysis and render side chain assignments
      less crucial for the success of the assignments. The application of the protocol
      has been demonstrated with FK506 binding protein (FKBP, molecular mass 12 kDa).

PMID- 12054619
TI  - Roles of lysine 219 and 255 residues in tobacco acetolactate synthase.
AB  - Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis
      of valine, leucine, and isoleucine. The ALS is the target of several classes of
      herbicides, including the sulfonylureas, the imidazolinones, and the
      triazolopyrimidines. The roles of three well-conserved lysine residues (K219,
      K255, K299) in tobacco ALS were determined using site-directed mutagenesis. The
      mutation of K219Q inactivated the enzyme and abolished the binding affinity for
      cofactor FAD. However, the secondary structure of the enzyme was not changed
      significantly by the mutation. Both mutants, K255F and K255Q, showed strong
      resistance to three classes of herbicides Londax (a sulfonylurea), Cadre (an
      imidazolinone), and TP (a triazolopyrimidine). In addition, there was no
      difference in the secondary structures of wALS and K255F. On the other hand, the
      mutation of K299Q did not show any significant effect on the kinetic properties
      or any sensitivity to the herbicides. These results suggest that Lys219 is
      located at the active site and is likely involved in the binding of FAD, and that
      Lys255 is located at a binding site common for the three herbicides in tobacco
      ALS.

PMID- 12054620
TI  - Zeta-crystallin displays strong selectivity for salicylic acid over aspirin.
AB  - Interaction of camel lens zeta-crystallin with aspirin was investigated by
      activity and fluorescence measurements. Aspirin minimally inhibited the
      oxidoreductase activity of the enzyme and weakly quenched its fluorescence.
      However, significant fluorescence quenching of zeta-crystallin coincided with the
      appearance of a fluorescence signal characteristic of salicylic acid thereby
      raising the possibility that salicylic acid might have been the moiety
      responsible for inhibition and fluorescence quenching. Direct fluorescence
      measurements showed that zeta-crystallin had a much higher affinity for salicylic
      acid than aspirin (K(i) of about 24 microM for salicylic acid versus 630 microM
      for aspirin). Salicylic acid was also far more effective in inhibiting zeta
      crystallin than aspirin (K(i) values were 23 microM versus 820 microM,
      respectively). Inhibition kinetics suggested that salicylic acid interacted with
      zeta-crystallin via a binding site that was distinct from that of NADPH.
      Salicylic acid also interacted with and quenched the fluorescence of camel lens
      alpha-crystallin suggesting a general mode of interaction with lens proteins.
      Within the normal therapeutic concentrations of salicylic acid or aspirin, only
      crystallin-salicylic acid interactions might be significant. These results showed
      that camel lens zeta- and alpha-crystallin exhibited remarkable selectivity for
      salicylic acid over aspirin, and thus, could be considered as salicylate-binding
      proteins.

PMID- 12054621
TI  - The dietary flavonoid quercetin modulates HIF-1 alpha activity in endothelial
      cells.
AB  - The mechanism of activation of the transcription factor hypoxia-inducible factor
      1 (HIF-1) has been studied extensively. Under normal cellular oxygen conditions
      protein levels of the alpha subunit (HIF-1 alpha) are kept low due to massive
      ubiquitination and subsequent proteosomal degradation. However, during hypoxia
      ubiquitination is inhibited, causing stabilisation of the HIF-1 alpha protein.
      HIF-1 alpha can then translocate to the nucleus and facilitate transcription of
      numerous target genes, the majority of which are involved in glycolysis and
      angiogenesis via heterodimerisation with the beta subunit (HIF-1 beta/ARNT).
      Until now hypoxia has been the only naturally occurring signal shown to activate
      this transcription factor. We report here that the dietary flavonoid quercetin
      also activates HIF-1 alpha in all steps of its activation pathway, in a manner
      similar to hypoxia. We found that quercetin, an inhibitor of Ser/Thr kinases,
      stabilises HIF-1 alpha and causes nuclear localisation of the protein in a
      transcriptionally active state. Taken together these results strongly indicate
      that the dietary flavonoid quercetin regulates HIF-1 function at normal oxygen
      concentrations.

PMID- 12054622
TI  - Osteoprotegerin secretion from prostate cancer is stimulated by cytokines, in
      vitro.
AB  - Osteoprotegerin (OPG), a member of the tumor necrosis receptor family, is
      produced by various tissues and inhibits osteoclast differentiation and activity.
      Since the metastasis of prostate cancer to bone often induces osteosclerosis, the
      possibility that these tumor cells secrete OPG is of interest. We have
      investigated whether the prostate cancer cell lines LNCaP, PC-3, and DU-145
      produce and secrete OPG in vitro and if the production might be regulated by
      cytokines involved in remodeling of bone. OPG transcripts were detected by RT-PCR
      in all cell lines. OPG in culture media was analyzed by ELISA. In all three
      lineages, treatment with tumor necrosis factor-alpha and interleukin-1 beta dose
      dependently (5-5000 pM) stimulated the OPG secretion. Treatment with tumor
      necrosis factor-beta in increasing concentrations (1-1000 pM) stimulated OPG
      secretion in PC-3 but had no effect on the DU-145 and LNCaP cells. Dexamethasone
      (100 pM) had a small, but not significant, inhibitory effect on OPG secretion
      from DU-145 and LNCaP. In human non-malignant prostate cells, used as controls,
      there was no effect of IL-1 or TNFs on the secretion rate of OPG.

PMID- 12054623
TI  - Cloning, sequencing, and functional studies of the rpoS gene from Vibrio harveyi.
AB  - The Vibrio harveyi rpoS gene which encodes an alternative sigma factor (sigma(s)
      or sigma(38)), has been cloned and characterized. The predicted protein sequence
      is closely related to RpoS proteins in other bacteria with up to 86% sequence
      identity. A rpoS null mutant of V. harveyi was constructed and the phenotype
      studied. Comparison of the properties of the V. harveyi wild type and rpoS
      deletion mutant showed that rpoS affected the ability of the cells to survive
      only under specific types of environmental stresses. The rpoS null mutant had a
      lower survival rate compared to the wild type parental strain at high
      concentrations of ethanol and in the stationary phase. In contrast to other
      bacteria, deletion of rpoS in V. harveyi did not affect the resistance of the
      cells to high osmolarity or hydrogen peroxide, suggesting the existence of
      alternative systems in V. harveyi responsible for resistance to these stresses.
      RpoS appears not to be involved in the control of luminescence in V. harveyi even
      though it is implicated in regulation of other acyl-homoserine dependent quorum
      sensing systems.

PMID- 12054625
TI  - OASIS is a transcriptional activator of CREB/ATF family with a transmembrane
      domain.
AB  - Murine OASIS is a putative CREB/ATF family transcription factor that is induced
      in gliosis, but its molecular role has not been determined. We have isolated the
      human OASIS gene and investigated the potential of OASIS protein as a
      transcriptional activator. We found that OASIS can activate transcription through
      box-B elements but not through the somatostatin CRE. OASIS contains a putative C
      terminal hydrophobic transmembrane domain, a typical structural feature for the
      transcription factors activated by regulated intramembrane proteolysis.
      Truncation of the OASIS transmembrane domain resulted in a significant increase
      in transcriptional activity and altered its subcellular localization from the
      endoplasmic reticulum to the nucleus. Western blot analysis of transfected cells
      identified OASIS polypeptides of 82 and 66 kDa. These results suggest that the
      transmembrane domain plays an important role in the regulation of transcriptional
      activation by OASIS.

PMID- 12054624
TI  - Molecular crosstalk between p70S6k and MAPK cell signaling pathways.
AB  - We report here for the first time that the specific MAPK kinase (MEK) inhibitor,
      PD-98059, completely knocked out granulocyte-macrophage colony-stimulating factor
      (GM-CSF)-stimulated MAPK activity but also partially inactivated the ribosomal
      kinase p70S6K. Since a connection between the two major signaling pathways,
      Ras/MEK/MAPK and PI3-K/p70S6K was suspected, experiments were designed to prove a
      molecular crosstalk between those. First, p70S6K protein could be co
      immunoprecipitated with anti-MAPK antibodies, MAPK protein was similarly present
      in anti-p70S6K immunoprecipitates, indicating close spatial proximity of both
      signaling molecules. Second, p70S6K enzymatic activity was found in anti-MAPK
      immunoprecipitates and MAPK in anti-p70S6K immunoprecipitates, being the latter
      activity higher in samples derived from GM-CSF-treated cells. Since an upstream
      activator of p70S6K, phosphatidylinositol (PI)3-kinase, has been associated to
      cell movement in phagocytic cells, we studied a possible participation of p70S6K
      in chemotaxis and whether MAPK had an input. Our data show that functional
      chemotaxis was inhibited by rapamycin, a specific p70S6K inhibitor, as well as by
      PD-98059. Thus, a connection between these two kinases extends from the molecular
      level to cell migration, a key functionality in non-proliferative, mature
      phagocytes such as neutrophils.

PMID- 12054626
TI  - Protein engineering and properties of human metalloproteinase and thrombospondin
      1.
AB  - This work generated many truncated proteins and Glu(385) to Ala (E(385)/A)
      mutants of the human metalloproteinase and thrombospondin 1 (METH-1 or ADAMTS1)
      and specific antibodies. METH-1 was an active endopeptidase and both the
      metalloproteinase and the disintegrin/cysteine-rich domains were required for the
      proteinase activity. A point mutation at the zinc-binding site (E(385)/A)
      abolished the catalytic activity. METH-1 protein function may be modulated
      through proteolytic cleavage at multiple sites. One 135 kDa species had an NH(2)
      terminal sequence of L(33)GRPSEEDEE. A species at 115 kDa and some other protein
      bands began with F(236)VSSHRYV(243), indicating that METH-1 proenzyme might be
      activated by a proprotein convertase such as furin by cleaving the R(235)-F(236)
      peptide bond. This cleavage was not an autocatalytic process since the E(385)/A
      mutants were also processed. Furthermore, a 52 kDa band with an NH(2)-terminal
      sequence of L(800)KEPLTIQV resulted from the digestion between the first and the
      second thrombospondin 1-like motifs in the spacer region of the extracellular
      matrix-binding domains.

PMID- 12054627
TI  - Crystal structure of the liganded anti-gibberellin A(4) antibody 4-B8(8)/E9 Fab
      fragment.
AB  - Gibberellins, a class of plant hormones, consist of more than 120 members. Only a
      few of them are recognized by a receptor that remains unknown. The haptenic mouse
      monoclonal antibody, 4-B8(8)/E9, was generated against gibberellin A(4) (GA(4))
      to recognize biologically active GA selectivity, and we attempted to confirm the
      binding properties between the antibody and GA(4). We carried out an X-ray
      crystallographic analysis of the 4-B8(8)/E9 Fab fragment complexed with GA(4) at
      a 2.8 A resolution by using the molecular replacement method. The crystal
      structure of the Fab fragment showed the typical immunoglobulin fold of the beta
      barrel structure which is the common motif of all antibodies. A small hapten
      combining site was made up of three heavy chain CDR loops. On the other hand,
      CDRs of the light chain did not interact directly with GA(4). The C/D rings of
      the GA(4) molecule were in van der Waals contact mainly with the aromatic side
      chain of Tyr100AH and Phe100BH of CDR-H3. The 3 beta-hydroxyl and 6 beta-carboxyl
      groups were, respectively, hydrogen-bonded to the main chain of Ala33H and to the
      Thr53H heavy chain.

PMID- 12054628
TI  - Anti-angiogenic effects of homocysteine on cultured endothelial cells.
AB  - High levels of homocysteine induce a sustained injury on arterial endothelial
      cells which accelerates the development of thrombosis and atherosclerosis. Some
      of the described effects of homocysteine on endothelial cells are features shared
      with an anti-angiogenic response. Therefore, we studied the effects of
      homocysteine on key steps of angiogenesis using bovine aorta endothelial cells as
      a model. Homocysteine decreased proliferation and induced differentiation.
      Furthermore, 5 mM homocysteine produced strong inhibitions of matrix
      metalloproteinase-2 and urokinase, two proteolytic activities that play a key
      role in extracellular matrix re-modeling, and decreased migration and invasion,
      other two key steps of angiogenesis. This study demonstrates that homocysteine
      can inhibit several steps of the angiogenic process.

PMID- 12054629
TI  - ADAMTS1 cleaves aggrecan at multiple sites and is differentially inhibited by
      metalloproteinase inhibitors.
AB  - ADAMTS1 is a secreted protein that belongs to the recently described ADAMTS (a
      disintegrin and metalloprotease with thrombospondin repeats) family of proteases.
      Evaluation of ADAMTS1 catalytic activity on a panel of extracellular matrix
      proteins showed a restrictive substrate specificity which includes some
      proteoglycans. Our results demonstrated that human ADAMTS1 cleaves aggrecan at a
      previously shown site by its mouse homolog, but we have also identified
      additional cleavage sites that ultimately confirm the classification of this
      protease as an 'aggrecanase'. Specificity of ADAMTS1 activity was further
      verified when a point mutation in the zinc-binding domain abolished its catalytic
      effects, and latency conferred by the prodomain was also demonstrated using a
      furin cleavage site mutant. Suppression of ADAMTS1 activity was accomplished with
      a specific monoclonal antibody and some metalloprotease inhibitors, including
      tissue inhibitor of metalloproteinases 2 and 3. Finally, we developed an activity
      assay using an artificial peptide substrate based on the interglobular domain
      cleavage site (E(373)-A) of rat aggrecan.

PMID- 12054630
TI  - Multiplex standardized RT-PCR for expression analysis of many genes in small
      samples.
AB  - Standardized RT-PCR (StaRT-PCR) enables numerical quantification as well as intra
      and inter-laboratory comparison of gene expression. Multiplex StaRT-PCR, using
      two rounds of amplification, was conducted on Stratagene Universal Reference RNA.
      In the first round, cDNA, competitive template (CT) mix, and primers for up to 96
      genes were amplified for varying numbers of cycles. Next, products from round one
      were diluted, combined with primers for one gene, and amplified for an additional
      35 cycles. No additional cDNA or CT mix was added. Expression values obtained by
      uniplex and multiplex StaRT-PCRs were highly correlated (R=0.993, p<0.001).
      Products from round one could be diluted as much as 100,000-fold and still be
      quantified following round two amplification. Thus, using multiplex StaRT-PCR, 96
      genes were measured in the same amount of cDNA typically used to measure one gene
      with uniplex StaRT-PCR. Multiplex StaRT-PCR was also used to measure 18 genes in
      the fine needle biopsy of a primary lung carcinoma.

PMID- 12054631
TI  - Psychological stress increases bilirubin metabolites in human urine.
AB  - Some authors have suggested that psychological stress induces the production of
      reactive oxygen species (ROS). Some studies have supported that bilirubin exerts
      anti-oxidative effects in vivo. However, it is not known whether ROS induced by
      psychological stress provoke bilirubin oxidation in vivo. We investigated if the
      concentration of bilirubin oxidative metabolite (BOM), a bilirubin oxidative
      metabolite, increased in urine from subjects exposed to psychological stress.
      Sixty healthy male volunteers working in a pharmaceutical company were divided
      into a Group I which did not attend a conference, a Group II which attended a
      conference but did not deliver a speech, and a Group III which attended a
      conference and delivered speeches in the presence of the company executives.
      Subjective stress was scored (self-rating score) after subjects in Group III
      delivered their speeches at the conference. Urine was collected on the next day.
      The BOM concentrations, as measured by enzyme-linked immunosorbent assay, were
      normalized to the urinary concentration of creatinine. The concentration of BOM
      in Group III was significantly higher compared to that in Groups I and II (p<0.01
      and p<0.05, respectively). Furthermore, in Group III, the concentration of BOM
      correlated with the self-rating stress score (r=0.53, p<0.01). These findings
      suggest that emotional stimuli are associated with an increase in the oxidative
      metabolites of bilirubin in human urine, and that BOMs could be useful markers of
      psychological stress.

PMID- 12054632
TI  - Pathogenesis of the deafness-associated A1555G mitochondrial DNA mutation.
AB  - The pathogenic mechanisms of the A1555G mitochondrial DNA mutation in the 12S
      rRNA gene, associated with maternally inherited sensorineural deafness, are
      largely unknown. Previous studies have suggested an involvement of nuclear
      factor(s). To address this issue cybrids were generated by fusing osteosarcoma
      cells devoid of mtDNA with enucleated fibroblasts from two genetically unrelated
      patients. Furthermore, to determine the contribution, if any, of the
      mitochondrial and nuclear genomes, separately or in combination, in the
      expression of the disease phenotype, transmitochondrial fibroblasts were
      constructed using control and patient's fibroblasts as nuclear donors and
      homoplasmic mutant or wild-type cybrids as mitochondrial donors. Detailed
      analysis of mutant and wild-type cybrids from both patients and
      transmitochondrial fibroblast clones did not reveal any respiratory chain
      dysfunction suggesting that, if nuclear factors do indeed act as modifier agents,
      they may be tissue-specific. However, in the presence of high concentrations of
      neomycin or paromomycin, but not of streptomycin, mutant cells exhibit a decrease
      in the growth rate, when compared to wild-type cells. The decrease did not
      correlate with the rate of synthesis or stability of mitochondrial DNA-encoded
      subunits or respiratory chain activity. Further studies are required to determine
      the underlying biochemical defect.

PMID- 12054633
TI  - Structural and functional significance of disulfide bonds in saxatilin, a 7.7 kDa
      disintegrin.
AB  - Saxatilin is a 7.7 kDa disintegrin that belongs to a family of homologous protein
      found in several snake venoms. Six disulfide bond locations of the disintegrin
      were determined by enzymatic cleavage and matrix-assisted-laser-desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF). Functional implications
      of the disulfide bonds related to the biological activity of saxatilin were
      investigated with recombinant protein species produced by site-directed
      mutagenesis of saxatilin. Several lines of experimental evidence indicated that
      three disulfide bonds, Cys21-Cys35, Cys29-Cys59, and Cys47-Cys67, of the
      disintegrin are closely associated with its biological function such as its
      ability to block the binding of integrin GPIIb-IIIa and alpha(v)beta(3) with
      fibrinogen and extracellular matrix. Those disulfide linkages were also revealed
      to be important for maintaining the functional structure of the protein molecule.
      On the other hand, the disulfide bridges of Cys6-Cys15 and Cys8-Cys16 do not
      appear to be critical for the molecular structure and function of saxatilin.

PMID- 12054634
TI  - Silent mutations affect in vivo protein folding in Escherichia coli.
AB  - As an approach to investigate the molecular mechanism of in vivo protein folding
      and the role of translation kinetics on specific folding pathways, we made codon
      substitutions in the EgFABP1 (Echinococcus granulosus fatty acid binding
      protein1) gene that replaced five minor codons with their synonymous major ones.
      The altered region corresponds to a turn between two short alpha helices. One of
      the silent mutations of EgFABP1 markedly decreased the solubility of the protein
      when expressed in Escherichia coli. Expression of this protein also caused strong
      activation of a reporter gene designed to detect misfolded proteins, suggesting
      that the turn region seems to have special translation kinetic requirements that
      ensure proper folding of the protein. Our results highlight the importance of
      codon usage in the in vivo protein folding.

PMID- 12054635
TI  - Affinity improvement of the high-affinity immunoglobulin E receptor by phage
      display.
AB  - The immunoglobulin E (IgE)-binding site of its high-affinity receptor is
      localized in the second immunoglobulin-like domain (D2) of the alpha-subunit (Fc
      epsilon RI alpha). In this study, the randomized pentapeptides were introduced
      between Glu(132) and Ile(138) of Fc epsilon RI alpha D2 and displayed on a
      filamentous phage. After eight rounds of panning, a phage clone having a mutation
      of Asp(135)Tyr(136)Met(137) in Fc epsilon RI alpha D2 was obtained. The binding
      affinity of the mutant phages to immobilized IgE was approximately 500 times
      higher than that of the wild type. The mutant phages competitively inhibited the
      binding of IgE to the soluble receptor at a 50% inhibition (IC(50)) value of 116
      pM. The mutant Fc epsilon RI alpha D2, which had been expressed as a fusion
      protein with glutathione S-transferase in Escherichia coli, also showed higher
      IgE-binding capacity than the wild type. The mutant Fc epsilon RI alpha D2 is
      expected to manifest its improved IgE-binding affinity together with any fusion
      partner.

PMID- 12054636
TI  - Effect of a peroxisome proliferator on 3 beta-hydroxysteroid dehydrogenase.
AB  - To better understand the changes that occur following exposure to peroxisome
      proliferators, we utilized mRNA differential display and microarray to screen for
      peroxisome proliferator target genes apart from those involved in lipid
      metabolism in male C57B6 mice by using the ubiquitous plasticizer, di(2
      ethylhexyl)phthalate (DEHP). One noted change was the dose-dependent suppression
      of the mouse hormone metabolizing 3 beta-hydroxysteroid dehydrogenase V (HSD3b5),
      which is specifically expressed in the male mouse liver. Northern analysis showed
      that HSD3b5 mRNA levels decreased dramatically upon one-day exposure to 2.0%
      dietary DEHP, and were nearly undetectable by one week of treatment. Food
      restriction also significantly suppressed HSD3b5 expression; however, in this
      case the suppression was delayed and to a lesser extent. Another mouse 3 beta
      hydroxysteroid dehydrogenase, HSD3b4, predominantly expressed in kidneys, was
      also regulated by DEHP and food restriction. The sex-specific gene, HSD3b5, was
      affected more by DEHP and food restriction than the tissue-specific gene, HSD3b4.

PMID- 12054637
TI  - Thyroid hormonal activity of the flame retardants tetrabromobisphenol A and
      tetrachlorobisphenol A.
AB  - The thyroid hormonal-disrupting activity of the flame retardants
      tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) was examined and
      compared with that of bisphenol A, a typical estrogenic xenobiotic. TBBPA and
      TCBPA, halogenated derivatives of bisphenol A, markedly inhibited the binding of
      triiodothyronine (T(3); 1 x 10(-10) M) to thyroid hormone receptor in the
      concentration range of 1 x 10(-6) to 1 x 10(-4) M, but bisphenol A did not. The
      thyroid hormonal activity of TBBPA and TCBPA was also examined using rat
      pituitary cell line GH3 cells, which grow and release growth hormone (GH)
      depending on thyroid hormone. TBBPA and TCBPA enhanced the proliferation of GH3
      cells and stimulated their production of GH in the concentration range of 1 x 10(
      6) to 1 x 10(-4) M, while bisphenol A was inactive. TBBPA, TCBPA, and bisphenol A
      did not show antagonistic action, i.e., these compounds did not inhibit the
      hormonal activity of T(3) to induce growth and GH production of GH3 cells. TBBPA
      and TCBPA, as well as bisphenol A, enhanced the proliferation of MtT/E-2 cells,
      whose growth is estrogen-dependent. These results suggest that TBBPA and TCBPA
      act as thyroid hormone agonists, as well as estrogens.

PMID- 12054639
TI  - Structural basis for inhibition of cyclin-dependent kinase 9 by flavopiridol.
AB  - Flavopiridol has been shown to potently inhibit CDK1 and 2 (cyclin-dependent
      kinases 1 and 2) and most recently it has been found that it also inhibits CDK9.
      The complex CDK9-cyclin T1 controls the elongation phase of transcription by RNA
      polymerase II. The present work describes a molecular model for the binary
      complex CDK9-flavopiridol. This structural model indicates that the inhibitor
      strongly binds to the ATP-binding pocket of CDK9 and the structural comparison of
      the complex CDK2-flavopiridol correlates the structural differences with
      differences in inhibition of these CDKs by flavopiridol. This structure opens the
      possibility of testing new inhibitor families, in addition to new substituents
      for the already known leading structures such as flavones and adenine
      derivatives.

PMID- 12054638
TI  - Intracerebroventricular interleukin-6 treatment decreases body fat in rats.
AB  - Recently we found that interleukin-6 (IL-6) knockout mice develop mature-onset
      obesity and that a single intracerebroventricular (ICV) injection of IL-6
      increases energy expenditure. In the present study we investigated if chronic ICV
      treatment with IL-6 can suppress body fat mass. IL-6 was injected ICV daily for
      two weeks to rats fed a high-fat diet. IL-6 treatment but not saline treatment
      decreased body weight by 8.4% and decreased the relative weights of mesenteric
      and retroperitoneal fat pads. Consistent with this, circulating leptin levels
      were decreased by 40% after IL-6 treatment but not after saline treatment.
      Average food intake per day was decreased in the IL-6 treated group compared to
      the saline treated rats. IL-6 treatment did not change hepatic expression of the
      acute-phase protein haptoglobin, serum levels of insulin or insulin-like growth
      factor-I, or the weights of the heart, liver, kidneys, adrenals, and spleen. We
      conclude that centrally administered IL-6 can decrease body fat in rats without
      causing acute-phase reaction.

PMID- 12054640
TI  - Use of a hydrophobic dye to indirectly probe the structural organization and
      conformational plasticity of molecules in amorphous aggregates of carbonic
      anhydrase.
AB  - Understanding protein aggregation may hold important clues to understanding what
      goes wrong with protein folding in neurodegenerative disorders and in bioreactors
      in which proteins are overexpressed. Unfortunately, aggregates tend to be
      intractable to most standard methods of biochemical investigation. Thus,
      relatively little is even now known about the micro- and macro-structural
      features of aggregates. To gain insights into the thermal aggregation of a model
      globular protein [bovine carbonic anhydrase (BCA)], we have used
      spectrofluorimetry to examine the binding of a hydrophobic dye, 8
      anilinonaphthalene sulfonate (ANS), to hydrophobic clusters on the protein's
      surface both before and after heat-induced aggregation and upon cooling. Whereas
      native BCA shows no surface hydrophobicity, thermally aggregated BCA displays
      significant hydrophobicity both in the heated state and upon cooling. The timing
      of the addition of ANS in the course of aggregation makes no net difference to
      the ANS bound; we argue that this suggests that aggregates are essentially
      porous. Cooling of aggregates results in a dramatic, fully reversible increase in
      ANS binding that cannot be explained by the temperature dependence of
      fluorescence quantum yield alone; we argue that the enhancement of fluorescence
      upon cooling indicates possible structural consolidation of unfolded regions
      within aggregates (akin to refolding), with the required structural
      reorganization being facilitated by porosity. Finally, implications of porosity
      in aggregates are discussed, in particular, for the possible immobilization of
      enzymes through fusion with aggregation-prone protein domains.

PMID- 12054641
TI  - EST-based identification of genes expressed in the liver of adult Atlantic salmon
      (Salmo salar).
AB  - A list of genes expressed in the liver of Atlantic salmon was compiled using the
      expressed sequence tag (EST) strategy. 733 ESTs, derived from 170 abundant and
      563 rare mRNA encoding liver cDNA clones, were determined. Bioinformatic analysis
      revealed that 390 (53%) of the salmon liver ESTs could be ascribed to the
      transcriptional products of 93 identified genes including 7 previously described
      in the Atlantic salmon. The identified Atlantic salmon genes were classified with
      respect to cellular role which showed that 33 (36%) of the identified genes
      encoded proteins associated with primary liver functions such as transport, acute
      phase response, and blood clotting. Furthermore, comparative analysis revealed
      that 12 of the 16 salmon genes that were shown to encode abundant mRNA
      transcripts in liver had homologues that have also been shown to be highly
      expressed in mammalian liver systems. Finally, two cDNA variants corresponding to
      the two cDNA forms of the apolipoprotein A-I gene previously identified in
      rainbow trout were also found in Atlantic salmon.

PMID- 12054642
TI  - Structural and functional characterization of hBD-1(Ser35), a peptide deduced
      from a DEFB1 polymorphism.
AB  - beta-Defensins are mammalian antimicrobial peptides that share a unique disulfide
      bonding motif of six conserved cysteines. An intragenic polymorphism of the DEFB1
      gene that changes a highly conserved Cys to Ser in the peptide coding region has
      recently been described. The deduced peptide cannot form three disulfide bonds,
      as one of the cysteines is unpaired. We have determined the cysteine
      connectivities of a corresponding synthetic hBD-1(Ser35) peptide, investigated
      the structure by circular dichroism spectroscopy, and assayed the in vitro
      antimicrobial activity. Despite a different arrangement of the disulfides, hBD
      1(Ser35) proved as active as hBD-1 against the microorganisms tested. This
      activity likely depends on the ability of hBD-1(Ser35) to adopt an amphipathic
      conformation in hydrophobic environment, similar to the wild type peptide, as
      suggested by CD spectroscopy.

PMID- 12054643
TI  - A rare protein fluorescence behavior where the emission is dominated by tyrosine:
      case of the 33-kDa protein from spinach photosystem II.
AB  - An abnormal fluorescence emission of protein was observed in the 33-kDa protein
      which is one component of the three extrinsic proteins in spinach photosystem II
      particle (PS II). This protein contains one tryptophan and eight tyrosine
      residues, belonging to a "B type protein". It was found that the 33-kDa protein
      fluorescence is very different from most B type proteins containing both
      tryptophan and tyrosine residues. For most B type proteins studied so far, the
      fluorescence emission is dominated by the tryptophan emission, with the tyrosine
      emission hardly being detected when excited at 280 nm. However, for the present
      33-kDa protein, both tyrosine and tryptophan fluorescence emissions were
      observed, the fluorescence emission being dominated by the tyrosine residue
      emission upon a 280 nm excitation. The maximum emission wavelength of the 33-kDa
      protein tryptophan fluorescence was at 317 nm, indicating that the single
      tryptophan residue is buried in a very strong hydrophobic region. Such a strong
      hydrophobic environment is rarely observed in proteins when using tryptophan
      fluorescence experiments. All parameters of the protein tryptophan fluorescence
      such as quantum yield, fluorescence decay, and absorption spectrum including the
      fourth derivative spectrum were explored both in the native and pressure
      denatured forms.

PMID- 12054644
TI  - Increased levels of tyrosinated alpha-, beta(III)-, and beta(IV)-tubulin isotypes
      in paclitaxel-resistant MCF-7 breast cancer cells.
AB  - Paclitaxel (PTX), the diterpene alkaloid, is a potent anti-cancer drug and is
      routinely used for the treatment of breast and ovarian cancers. The cellular
      targets of PTX are microtubules, which are composed of alpha- and beta-tubulin.
      Development of PTX resistance in patients has been a major problem associated
      with cancer chemotherapy. In an effort to get insight into this phenomenon of
      drug resistance, a PTX-resistant cell line from MCF-7 breast cancer cells has
      been generated. Western analysis of the cell extracts revealed that the resistant
      cells contain 2-fold higher amount of tyrosinated alpha-tubulin than those of the
      wild-type MCF-7 cells. Similar analyses of beta-tubulin with the isotype-specific
      monoclonal antibodies demonstrated that the PTX-resistant cells contain 2.5-fold
      higher amounts of beta(III) and 1.5-fold higher amount of beta(IV)-tubulin, while
      no difference was observed in the level of beta(I) isotype. These results
      demonstrate for the first time that PTX resistance is associated with an increase
      in the level of tyrosinated alpha-tubulin.

PMID- 12054645
TI  - Analysis of the migration behaviour of single microtubules in electric fields.
AB  - By video contrast microscopy, individual microtubules formed from pure tubulin in
      the presence of taxol were studied in constant electric fields. At nearly
      physiological conditions, i.e., in a buffer at pH 6.8 and 120 mM ionic strength,
      suspended microtubules moved towards the anode with an electrophoretic mobility
      of approximately 2.6 x 10(-4) cm(2)/V s, corresponding to an unbalanced negative
      charge of 0.19 electron charges per tubulin dimer. Strikingly, this value is
      lower by a factor of at least 50 than that calculated from crystallographic data
      for the non-assembled tubulin dimer. Moreover, the taxol-stabilized microtubules
      had an isoelectric point of about pH 4.2 which is significantly lower than that
      known for the tubulin monomers. This indicates that microtubule formation is
      accompanied by substantial changes of charge distribution within the tubulin
      subunits. Constant electric fields were shown to affect also the orientation of
      microtubules gliding across a kinesin-coated surface at pH 6.8.

PMID- 12054646
TI  - Regulation of protein phosphatase 2A by hydrogen peroxide and glutathionylation.
AB  - The regulation of protein phosphatase 2A (PP2A) and protein threonine
      phosphorylation by H(2)O(2) was determined in Caco-2 cell monolayer. Incubation
      with H(2)O(2) (20 microM) resulted in threonine phosphorylation of a cluster of
      proteins at the molecular mass range of 170-250 kDa. PKC activity and plasma
      membrane localization of several isoforms of PKC were not affected by H(2)O(2).
      However, H(2)O(2) reduced 80-85% of okadaic acid-sensitive protein phosphatase
      activity. Immunocomplex protein phosphatase assay demonstrated that H(2)O(2)
      reduced the activity of PP2A, but not that of PP2C or PP1. Oxidized glutathione
      inhibited PP2A activity in plasma membranes prepared from Caco-2 cells and the
      phosphatase activity of an isolated PP2A. PP2A activity was also inhibited by N
      ethylmaleimide, iodoacetamide, and p-chloromercuribenzoate. Inhibition of PP2A by
      oxidized glutathione was reversed by reduced glutathione. Glutathione also
      restored the PP2A activity in plasma membranes isolated from H(2)O(2)-treated
      Caco-2 cell monolayer. These results indicate that PP2A activity can be regulated
      by glutathionylation, and that H(2)O(2) inhibits PP2A in Caco-2 cells, which may
      involve glutathionylation of PP2A.

PMID- 12054647
TI  - Up-regulation of PDCD4 in senescent human diploid fibroblasts.
AB  - Programmed cell death 4 (PDCD4) has a common MI domain sharing with death
      associated protein 5 (DAP5) and a component of eukaryotic translation initiation
      factor (eIF4G) complex and it might also work as a tumor suppressor. We could
      find that the message and product of Pdcd4 gene were up-regulated in senescent
      human diploid fibroblasts. In yeast two hybrid analysis, the C-terminal region of
      PDCD4 interacted with ribosomal protein S13 (RPS13), ribosomal protein L5 (RPL5),
      and TI-227H. In in vitro binding assay, RPS13, a component of 40S ribosome was
      stably bound to PDCD4. We also found that PDCD4 was localized to polysome
      fractions. We could pull out eIF4G with GST-PDCD4, but eIF4E did not interact
      with PDCD4. From these results, we could assume that PDCD4 might regulate the
      eIF4G-dependent translation through direct interactions with eIF4G and RPS13 in
      senescent fibroblasts.

PMID- 12054648
TI  - Leptin mediates a proliferative response in human MCF7 breast cancer cells.
AB  - Obesity is a risk factor of breast cancers. As leptin, a hormone mainly secreted
      by white adipocytes, elicits proliferative effects in some cell types, we tested
      the hypothesis that leptin could influence human breast cancer MCF-7 cell growth.
      Here we show that MCF-7 cells express leptin receptors and respond to human
      recombinant leptin by STAT3 and p42/p44 MAPkinase activations and by increased
      proliferation. These findings suggest that leptin could act in vivo as a
      paracrine/endocrine growth factor towards mammary epithelial cells thus
      contributing to explain why obesity is a risk factor of developing breast
      cancers.

PMID- 12054649
TI  - Polymorphism in exon 4 of the human 3 beta-hydroxysteroid dehydrogenase type I
      gene (HSD3B1) and blood pressure.
AB  - There is growing evidence to the effect that steroid hormones are associated with
      a complex phenotype of metabolic abnormalities usually referred to as the
      metabolic syndrome. The 3 beta-hydroxysteroid dehydrogenases/Delta(4,5)-isomerase
      (3 beta-HSD) is crucial to the biosynthesis of hormonal steroids, including
      aldosterone, cortisol, and testosterone. The objective of the present study was
      to examine the potential impact of a T-->C substitution at codon Leu(338) of the
      type I (HSD3B1) 3 beta-HSD gene on obesity, circulating hormones, and estimates
      of insulin, glucose, and lipid metabolism as well as blood pressure in 284
      unrelated Swedish men born in 1944. The subjects were genotyped by using PCR
      amplification of exon 4 of the HSD3B1 gene followed by digestion with the
      restriction enzyme BglII. The frequency of allele T was 0.44 and that of allele C
      0.56. Homozygotes for the C allele (n=75) had significantly (P<0.05) higher mean
      systolic and diastolic blood pressures compared to both heterozygotes (n=143) and
      homozygotes for the T allele (n=45). In addition, the C allele was significantly
      (P=0.018) more frequent among subjects with grade 1 hypertension (>140/90 mm Hg)
      compared to normotensive (<130/85 mm Hg) subjects. These results were all
      adjusted for the potential confounding effect of body mass index (BMI) and waist
      to-hip ratio (WHR). Other measurements such as BMI, WHR, abdominal sagittal
      diameter, salivary cortisol, total testosterone, serum leptin, fasting insulin
      and glucose, and serum lipids were not different across the HSD3B1 genotype
      groups. In conclusion, a T-->C polymorphism at codon Leu(338) of exon 4 of the
      HSD3B1 gene is associated with elevated systolic and diastolic blood pressures.
      The pathogenic mechanism underlying this association is, however, uncertain from
      the present data and further studies are warranted.

PMID- 12054650
TI  - Probing the specificity of a trypanosomal aromatic alpha-hydroxy acid
      dehydrogenase by site-directed mutagenesis.
AB  - The aromatic l-alpha-hydroxy acid dehydrogenase (AHDAH) from Trypanosoma cruzi
      has over 50% sequence identity with cytosolic malate dehydrogenases (cMDHs), yet
      it is unable to reduce oxaloacetate. Molecular modeling of the three-dimensional
      structure of AHADH using the pig cMDH as template directed the construction of
      several mutants. AHADH shares with MDHs the essential catalytic residues H195 and
      R171 (using Eventoff's numbering). The AHADH A102R mutant became able to reduce
      oxaloacetate, while remaining fully active towards aromatic alpha-oxoacids. The
      Y237G mutant diminished its affinity for all of the natural substrates, whereas
      the double mutant A102R/Y237G was more active than Y237G and had similar activity
      with oxaloacetate and with aromatic substrates. The present results reinforce our
      proposal that AHADH arose by a moderate number of point mutations from a cMDH no
      longer present in the parasite.

PMID- 12054651
TI  - Translocation of pleckstrin requires its phosphorylation and newly formed
      ligands.
AB  - Pleckstrin is the major substrate of protein kinase C (PKC) in platelets. We
      sought to determine whether pleckstrin phosphorylation is sufficient to target
      the soluble protein to binding sites. Permeabilization of platelets by
      streptolysin O (SLO) was used to separate bound and soluble pleckstrin. Platelets
      were incubated with phorbol 12-myristate 13-acetate (PMA) and/or guanosine 5'
      [gamma-thio]triphosphate (GTP[S]) in the presence of [gamma-(32)P]ATP and SLO.
      PMA stimulated pleckstrin phosphorylation, but this pleckstrin diffused from
      permeabilized platelets. Addition of GTP[S] with PMA caused up to 40-50% of
      pleckstrin to be retained within platelets and enhanced secretion of platelet 5
      hydroxytryptamine. PKC alpha pseudosubstrate peptide inhibited pleckstrin
      phosphorylation, the binding of pleckstrin and secretion. After extraction of
      permeabilized platelets containing bound pleckstrin with Triton X-100, the
      protein was solubilized. Thus, phosphorylated pleckstrin was retained in
      platelets only after activation of GTP-binding proteins that stimulate the
      formation of membrane-bound pleckstrin ligands. Translocation of pleckstrin may
      facilitate the associated secretion.

PMID- 12054652
TI  - Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3.
AB  - Phospholipase C (PLC)-beta enzymes (isoenzymes beta 1-beta 4) are activated by G
      protein subunits, leading to the generation of intracellular messengers which
      mobilize calcium and activate protein kinase C. It has recently been recognized
      that these enzymes interact with and are regulated by proteins other than G
      proteins. Using the yeast two-hybrid technique to screen a leukocyte library we
      identified mitogen-activated protein kinase kinase 3 (MKK3) as a partner of PLC
      beta 2. The interaction was confirmed by co-immunoprecipitation assays which
      indicated that MKK3 interacts with PLC-beta 2, but not with other PLC-betas. PLC
      beta 2 interacted weakly with MKK6, which is related to MKK3, but not with the
      other MKK3 tested. The region of PLC-beta 2 involved in the interaction with MKK3
      was mapped to the C-terminus of PLC-beta 2. p38MAPK also co-immunoprecipitated
      with PLC-beta 2. The data suggest that PLC-beta 2 serves an unappreciated role
      assembling components of the p38MAPK signaling module.

PMID- 12054653
TI  - Enhancement of tolerance to heavy metals and oxidative stress in Dunaliella
      tertiolecta by Zn-induced phytochelatin synthesis.
AB  - The synthesis of phytochelatins (PCs) in a marine alga, Dunalliela tertiolecta,
      is strongly induced by Zn. Pretreatment of the cells with Zn enhances the
      tolerance toward toxic heavy metals such as Cd, Hg, Cu, Pb, and arsenate.
      Moreover, the pretreatment also increases the tolerance toward oxidative stress
      caused by hydrogen peroxide or paraquat. In vitro analysis shows that PC is a
      stronger scavenger of hydrogen peroxide and superoxide radical than glutathione.
      These results suggest that PCs inducibly synthesized by Zn treatment could play a
      role not only in detoxification of heavy metals but also in mitigation of
      oxidative stress.

PMID- 12054654
TI  - KCl activates mitogen-activated protein kinase in rabbit bailar artery.
AB  - The objective of the present study was to investigate if MAPK can be activated by
      a non-receptor agonist KCl, which depolarizes membrane to increase intracellular
      Ca(2+) and contracts cerebral arteries. Rabbit basilar arteries were used in
      isometric tension and western blot analysis studies. KCl produced a concentration
      dependent contraction and an elevation of phospho-MAPK, which can be abolished by
      nicardipine, a voltage-dependent Ca(2+) channel blocker, and by PD98059 or U0126,
      MAPK kinase inhibitors. Thus, MAPK can be activated by the elevation of
      intracellular Ca(2+), independent of the activation of either G-protein coupled
      receptors or receptor tyrosine kinase. KCl which not only depolarizes membrane
      potentials, opens voltage-dependent Ca(2+), and increases intracellular Ca(2+),
      but also, probably by elevation of intracellular Ca(2+), triggers the activation
      of MAPK which seems responsible for a predominant part of the contraction of KCl
      in the rabbit basilar arteries.

PMID- 12054655
TI  - Alpha-tocopheryl succinate epitomizes a compound with a shift in biological
      activity due to pro-vitamin-to-vitamin conversion.
AB  - With the advent of the third millennium, a number of pathologies have been
      eradicated or taken under control. However, the incidences, of cancer and
      atherosclerosis, the two most common causes of death in developed countries, have
      increased or, in some instances, only stagnated. Therefore there has been an
      intensive search for agents effective against such life-threatening conditions.
      Accordingly, the potential anti-atherogenic activity of vitamin E analogs has
      been studied extensively. Interestingly, recent reports strongly suggest that
      certain vitamin E analogs, represented in particular by alpha-tocopheryl
      succinate (alpha-TOS), also possess anti-neoplastic activity. In this
      communication, we review our current understanding of the molecular basis for
      these double effects of alpha-TOS and propose a testable hypothesis, according to
      which this semi-synthetic analog exerts both anti-atherogenic and anti-neoplastic
      activities. We propose that the prevalence of each activity depends on the actual
      form of the vitamin E analog. That is, the conversion of the pro-vitamin E form,
      alpha-TOS, to the corresponding vitamin form, alpha-tocopherol, makes this anti
      neoplastic agent active against inflammatory diseases like atherosclerosis.

PMID- 12054656
TI  - ASC, which is composed of a PYD and a CARD, is up-regulated by inflammation and
      apoptosis in human neutrophils.
AB  - ASC is an adaptor protein that is composed of two protein-protein interaction
      domains, a PYRIN domain (PYD), and a caspase-recruitment domain (CARD). Recently,
      ASC was identified as a binding partner of pyrin, which is the product of MEFV, a
      gene causing familial Mediterranean fever (FMF). Mutations in MEFV result in
      defects in control of neutrophil-mediated inflammation. Thus we focused on the
      expression of ASC in neutrophils. Immunohistochemical study showed that ASC is
      increased in neutrophils in severe inflammatory sites of gangrenous appendicitis.
      We, then, tested whether proinflammatory mediators induce ASC using peripheral
      blood neutrophils in vitro. ASC expression was transiently up-regulated by IL
      1alpha, IL-1beta, IFN-alpha, IFN-gamma, TNFalpha, and LPS. ASC was also increased
      by incubation with either anti-Fas antibody or recombinant soluble Fas ligand.
      The Fas-mediated induction of ASC was inhibited by a general caspase inhibitor, z
      VAD-fmk, and an immunocytochemical study showed that ASC was increased in
      neutrophils exhibiting characteristic phenotypes for apoptosis. These findings
      suggest that up-regulation of ASC is closely associated with inflammation and
      apoptosis in neutrophils.

PMID- 12054657
TI  - Interaction of Btk and Akt in B cell signaling.
AB  - Reactive oxygen species (ROS) or reactive oxygen intermediates (ROIs) mediate
      complex signaling involving multiple pathways. In this report, we demonstrate for
      the first time that endogenous Bruton's tyrosine kinase (Btk) and Akt can
      interact with each other in DT40 chicken B cells and human Nalm6 B cells and that
      this interaction is inducible following H2O2 stimulation. This interaction is
      supported by visualizing the co-localization of Btk and Akt in the perinuclear
      region and membrane ruffles in COS-7 cells. We have also shown the involvement of
      phosphatidylinositol 3-kinase (PI 3-K) and Btk in the phosphorylation of Akt
      following stimulation by hydrogen peroxide (H2O2). Interestingly, Akt
      phosphorylation was found in the presence of Btk even in the absence of oxidative
      stress. In addition, we have investigated the involvement of PI 3-K in the MAPKs
      and ERK and JNK phosphorylation, in the presence or absence of Btk.
      Phosphorylation of both ERK and JNK increased when the PI 3-K pathway was
      inhibited and both pathways were modulated positively by Btk. Taken together,
      based on the study of endogenous conditions, we show the novel interaction of Btk
      and Akt in H2O2 signaling in B cells.

PMID- 12054658
TI  - Oxidized low density lipoprotein induces the cyclin-dependent kinase inhibitor
      p21(waf1) and the tumor suppressor Rb.
AB  - Oxidized low density lipoprotein (OxLDL) is known to be cytotoxic towards
      different cell types of the arterial wall, leading to progression of an
      atherosclerotic plaque. We previously reported that OxLDL activates the tumor
      suppressor p53 in human fibroblasts [Biochem. Biophys. Res. Commun. 276 (2000)
      718]. In the present work, we demonstrate that OxLDL increased intracellular
      levels of the kinase inhibitor p21(waf1) (p21) and of the tumor suppressor Rb.
      Concomitantly, level of the hypophosphorylated active form of Rb (HypoP-Rb) was
      also enhanced. Cycloheximide prevented the OxLDL-induced increase in p21, Rb, and
      HypoP-Rb, whereas okadaic acid had no effect. This increase was also prevented by
      the antioxidant vitamin E. In addition, the lipid extract of OxLDL, which
      includes the lipid peroxidation products, reproduced the action of the OxLDL
      particle itself. OxLDL and its lipid extract induced an oxidative stress, as
      assessed by the intracellular levels of reactive oxygen species and lipid
      peroxidation products. Finally, OxLDL induced a dose-dependent inhibition of DNA
      synthesis as assessed by thymidine incorporation. These results demonstrate that
      OxLDL or its lipid peroxidation products, by generation of an oxidative stress,
      enhances the expression of p21 and Rb genes, leading to an accumulation of the
      Hypo-P active form of the tumor suppressor Rb. This phenomenon is in accordance
      with the fact that p21 is a mediator of p53-dependent cell-cycle arrest in G1 and
      is most probably involved in the cytotoxicity of OxLDL.

PMID- 12054660
TI  - Selective binding of trisamine-modified phosphorothioate antisense DNA to target
      mRNA improves antisense activity and reduces toxicity.
AB  - Antisense activity in living cells has been thought to occur via a mechanism
      involving both DNA-mediated hybridization arrest of target mRNA and RNase H
      mediated mRNA digestion. Therefore an ideal antisense agent should be permeable
      to the cell and possess capacities (1) to form a thermally stable duplex in vivo
      with its target, (2) to discriminate between mRNAs with different degrees of
      complementarity, and (3) to form antisense/RNA complexes that are susceptible to
      RNase H hydrolysis. A trisamine-modified deoxyuridine derivative of a novel
      phosphorothioate DNA 15-mer that meets all these criteria is described here.
      Compared with the unmodified phosphorothioate oligomer, the phosphorothioate
      derivative exhibits a higher antisense activity as well as reduced cytotoxicity
      in cells infected with HIV-1. Our data suggest that the melting temperature
      (T(m)) between antisense DNA and the target mRNA is not only one of the factors
      contributing to this derivative's improved antisense activity. Also important are
      an enhanced ability to discriminate between sequences and an increased
      susceptibility of the DNA/mRNA complex to RNase H hydrolysis. These results will
      be useful in designing more active, clinically useful antisense drugs.

PMID- 12054659
TI  - Different regulation of the LXRalpha promoter activity by isoforms of
      CCAAT/enhancer-binding proteins.
AB  - LXRs have recently been shown to regulate key enzymes in cholesterol degradation,
      reverse transport of cholesterol from peripheral cells, cholesterol uptake and
      lipogenesis. The LXRalpha promoter was thus studied to investigate if LXRalpha
      gene expression is under the regulation of transcription factors involved in
      adipogenesis. We report that the C/EBP transcription factor interacts with the
      promoter of the LXRalpha gene. In in vitro footprinting experiments, protein
      extracts from several tissues gave footprints covering a putative C/EBP
      recognition site. Transfection experiments and EMSA showed a direct effect of
      these transcription factors on the LXRalpha promoter. C/EBPalpha upregulated
      expression of the reporter gene in an NIH 3T3-L1 preadipocyte cell line, while
      C/EBPbeta and C/EBPdelta had no effect. In liver hepatoma Fao II and Cos-7 kidney
      cells, both C/EBPalpha and C/EBPbeta downregulated expression of the reporter
      gene while C/EBPdelta induced activity, indicating that the functional
      consequences of C/EBP isoform interactions with the LXRalpha promoter are
      dependent on the cellular context. Monitoring of the LXR mRNA levels during
      adipose tissue differentiation showed that LXRbeta is constitutively expressed
      during the entire differentiation process while LXRalpha is induced upon addition
      of differentiation mix.

PMID- 12054661
TI  - Some human B and T cell epitopes of bovine serum albumin, the major beef
      allergen.
AB  - Bovine serum albumin (BSA) is the major beef allergen. Since IgE and T cell
      recognitions are central to the specific immune response to allergens, the
      identification and immunologic characterization of B and T cell epitopes of BSA
      represent important steps in the development of treatments for beef allergy.
      Prior to our experiments, we hypothesized that BSA-specific antibodies and T
      cells react primarily with sequential epitopes in which the amino acid sequences
      differ greatly between bovine and human albumin. To clarify this hypothesis, 16
      peptides corresponding to such regions were synthesized as candidate epitopes.
      Among them, at least two regions, aa336-345 and aa451-459, were found to be B
      cell (IgE-binding) epitopes. In inhibition ELISA experiments, EYAV (aa338-341)
      and LILNR (aa453-457) bound to patient IgE antibodies and were found to be the
      cores of the IgE-binding epitopes. Three regions, DDSPDLPKLKPDPNTLC (aa107-123),
      PHACYTSVFDKLKHLVDEP (aa364-382), and LSLILNRLC (aa451-459), were found to induce
      T cell proliferation in more than half of the patients tested. Of interest was
      that these three regions were also recognized by B cells. Information concerning
      human B and T cells epitopes can contribute greatly to the elucidation of the
      etiology of beef allergy.

PMID- 12054662
TI  - Esterification of the propionate groups promotes alpha/beta hemoglobin chain
      homogeneity of CN-hemin binding.
AB  - This study examines the post-translational role of peripheral propionate groups
      in the incorporation of the Fe-protoporphryin IX heme into nascent alpha- and
      beta-globin chains. Human apohemoglobin (a heme-free alpha/beta dimer) in 0.05 M
      potassium phosphate buffer, pH 7, at 20 degrees C was titrated with either CN
      protohemin (native heme with two peripheral propionate groups), or CN
      dimethylester hemin (a modified heme with two methyl ester groups in place of the
      propionate groups). Soret spectrophotometric CN-hemin titrations confirmed that a
      spectral shift resulted upon binding of protohemin, but no spectral shift
      occurred upon binding the dimethylester derivative. Recent studies have
      correlated a Soret spectral shift with the preferential heme binding to the alpha
      subunit of apohemoglobin. The absence of a Soret wavelength shift (in conjunction
      with molecular modeling) presented here suggested that the modification of heme
      propionate groups prevented the formation of an alpha-heme/beta-globin
      intermediate, a requisite step in the normal assembly of functional hemoglobin.

PMID- 12054663
TI  - Platelet-activating factor (PAF) activates casein kinase 2 in the protozoan
      parasite Herpetomonas muscarum muscarum.
AB  - Herpetomonas muscarum muscarum is a flagellate parasite of the family
      Trypanosomatidae, whose cell differentiation can be triggered by the lipid
      mediator, PAF. In this study we demonstrate for the first time that PAF effect
      relies on the activation of casein kinase 2 (CK2). The classical antagonist of
      PAF receptor, WEB 2086, abrogated PAF-enhanced CK2 activity. CK2 activation by
      PAF was also inhibited when parasite extracts were assayed in the presence of
      modulators of PKC, MAPK, and both Ser/Thr and Tyr phosphatases. Finally, a cell
      permeable inhibitor of CK2 (DRB) suppressed PAF-induced cell differentiation in a
      dose-dependent manner.

PMID- 12054664
TI  - Establishment of a monoclonal antibody against human Toll-like receptor 3 that
      blocks double-stranded RNA-mediated signaling.
AB  - A monoclonal antibody (mAb) against human Toll-like receptor (TLR) 3 was
      established and its effect on TLR3-mediated responses was tested using human
      fibroblast cell lines expressing TLR3 on the cell surface. Fibroblasts are known
      to produce IFN-beta upon viral infection or treatment with double-stranded RNA
      (dsRNA) through distinct signaling pathways. Here, we show the mAb to TLR3
      suppressed poly(I):poly(C)-mediated IFN-beta production by human fibroblasts
      naturally expressing TLR3 on their surface. By reporter gene assay using HEK293
      cells transfected with a human TLR3 expression vector, TLR3 recognized dsRNA to
      activate NF-kappaB and the IFN-beta promoter. TLR3 signaling was not elicited by
      either single-stranded RNA (ssRNA) or dsDNA. Thus, specific recognition of dsRNA
      by extracellular TLR3 is essential for induction of type I IFN: the
      interassociation between dsRNA and TLR3, regardless of direct or indirect
      binding, should be disrupted by mAb being attached to TLR3. The mAb against TLR3
      reported herein may serve as a regulator for virus-mediated immune response via
      an alternative pathway involving the dsRNA-TLR3 recognition which might occur on
      host cells.

PMID- 12054665
TI  - Inhibitors of antibiotic efflux pump in resistant Enterobacter aerogenes strains.
AB  - Enterobacter aerogenes, a nosocomial pathogen, is frequently exhibiting multidrug
      resistance mechanisms associated with a change in membrane permeability. In
      clinical isolates, active efflux plays a prominent role in antibiotic resistance.
      We report here the effect of three unrelated compounds that are able to restore a
      noticeable antibiotic susceptibility to resistant strains. The targeting of
      various parameters which contribute to the efficacy of the efflux mechanism, such
      as energy, flux selectivity, or functional assembly of the membrane complex,
      increases the intracellular chloramphenicol concentration in resistant isolates.

PMID- 12054666
TI  - Characterization of the chondroitin sulfates in wild type Caenorhabditis elegans.
AB  - The purpose of this study was to isolate and characterize the GAGs from the wild
      type nematode Caenorhabditis elegans in preparation for the characterization of
      the transgenic form constructed by Link [Proc. Natl. Acad. Sci. USA 92 (1995)
      9368] which expresses various forms of beta-peptide (or A4 peptide). This peptide
      forms deposits very similar to the ones found in the neuritic plaques and
      neurofibrillary tangles in Alzheimer disease (AD). Characterization has been
      accomplished by degradation with specific enzymes and analysis of the products by
      TLC and HPLC. The results were compared with earlier works and shown to differ in
      disaccharide content.

PMID- 12054667
TI  - Cardiac ankyrin repeat protein, a negative regulator of cardiac gene expression,
      is augmented in human heart failure.
AB  - The technique of representational difference analysis of cDNA has been applied to
      screen for differentially expressed genes in a canine model of pacing-induced
      heart failure. We identified the canine homolog of the cardiac ankyrin repeat
      protein (CARP) which has been shown to be involved in the regulation of the
      transcription of cardiac genes. To confirm the significance for human heart
      failure, cardiac tissue specimens obtained from non-failing donor hearts and from
      explanted hearts from patients with end-stage heart failure were investigated.
      CARP mRNA and protein levels were markedly increased in failing left ventricles.
      Interestingly, alterations in CARP expression were restricted to ventricular
      tissue and were not observed in atria. Fractionation experiments revealed that
      CARP was expressed predominantly in the nuclei consistent with the proposed
      function of CARP as a modulator of transcription. Together, these findings raise
      the possibility that augmented ventricular CARP expression may play a role in the
      pathogenesis of human heart failure.

PMID- 12054668
TI  - Activation of Ras cascade increases the mitochondrial enzyme content of
      respiratory competent yeast.
AB  - We investigated the effects of genetic and physiological modulations of the cAMP
      protein kinase A pathway on mitochondrial biogenesis of yeast cells grown on
      lactate. Yeast mutants with over-activated Ras/adenylate cyclase pathway (i.e.,
      Ras2(val19), ira1Delta(ira2)Delta) or with a constitutive downstream activation
      of protein kinases A (i.e., bcyDelta) showed an increase in the mitochondrial
      enzyme content. In contrast, loss of Ras activity (i.e., Ras2 mutant) resulted in
      a slight decrease. The treatment by cAMP of a responsive mutant increased the
      oxidative phosphorylation capacity of cells and increased the transcript level of
      nuclear genes encoding for mitochondrial proteins. In contrast, the transcript
      level of mitochondrial DNA genes was unchanged. It is concluded that the
      Ras/cAMP/protein kinase A pathway is part of the regulatory circuit controlling
      biogenesis of the oxidative phosphorylation complexes in yeast cells.

PMID- 12054669
TI  - Hsc62, Hsc56, and GrpE, the third Hsp70 chaperone system of Escherichia coli.
AB  - Hsc62 is the third Hsp70 homolog of Escherichia coli, which we found previously.
      Hsc62 is structurally and biochemically similar to DnaK, but hscC gene encoding
      Hsc62 did not compensate for the defects in the dnaK-null mutant of E. coli
      MC4100 strain. We cloned the ybeV gene and purified the gene product named Hsc56,
      a 55,687-Da protein with a J-domain like sequence. Hsc56 stimulated the ATPase
      activity of only Hsc62 but not those of the other Hsp70 homologs, DnaK and Hsc66.
      Hsc56 contains the -His-Pro-Glu- sequence corresponding to the His-Pro-Asp motif
      in DnaJ, which is indispensable for DnaJ to interact with DnaK. Conversion of 
      His-Pro-Glu- to -Ala-Ala-Ala- abolished the ability of Hsc56 to stimulate the
      ATPase activity of Hsc62. GrpE, a nucleotide exchange factor for DnaK, also
      stimulated the ATPase activity of Hsc62 in the presence of Hsc56. Hsc62-Hsc56
      GrpE is probably a new Hsp70 chaperone system of E. coli.

PMID- 12054670
TI  - CARP is a novel caspase recruitment domain containing pro-apoptotic protein.
AB  - Many CARD-containing caspase mediators interact with CARD-containing caspases and
      participate in activation or suppression of caspases. We cloned a novel CARD
      containing protein from our EST database, named CARP. Computational
      characterization revealed that CARP encoded 445 amino acids with predicted MW
      49.7 kDa, localized at chromosome 10p13 with 15 exons, and four putative function
      domains, one CARD domain (aa 160-243), one nuclear receptor-binding motif, two EF
      hand motifs, and 42% alpha-helix content. Stable transfection of CARP into lung
      carcinoma A549 and HEK293S cells leads to 23% of the cells undergoing apoptosis,
      but only 3% in the cells transfected with empty control vector. The cell
      proliferation was significantly inhibited by 1.2-5 folds (P<0.02) in seven CARP
      transfected tumor cell lines-lung carcinoma A549 and PG, melanoma WM451, prostate
      cancer PC-3 and PC-3M, liver cancer H7402, and bladder cancer BIU87. Our results
      suggest that CARP is a novel CARD-containing pro-apoptotic protein.

PMID- 12054671
TI  - Mice with cardiac-specific sequestration of the beta-subunit of the L-type
      calcium channel.
AB  - The beta subunit of the L-type voltage-dependent calcium channel modifies the
      properties of the channel complex by both allosteric modulation of the alpha1
      subunit function and by chaperoning the translocation of the alpha1 subunit to
      the plasma membrane. The goal of this study was to investigate the functional
      effect of changing the in vivo stoichiometry between the alpha1 and beta subunits
      by creating a dominant negative expression system in a transgenic mouse model.
      The high affinity beta subunit-binding domain of the alpha1 subunit was
      overexpressed in a cardiac-specific manner to act as a beta subunit trap. We
      found that the predominant beta isoform was located primarily in the membrane
      bound fraction of heart protein, whereas the beta1 and beta3 were mostly
      cytosolic. There was a significant diminution of the amount of beta2 in the
      membrane fraction of the transgenic animals, resulting in a decrease in
      contractility of the heart and a decrease in L-type calcium current density in
      the myocyte. However, there were no distinguishable differences in beta1 and
      beta3 protein expression levels in the membrane bound fraction between transgenic
      and non-transgenic animals. Since the beta1 and beta3 isoforms only make up a
      small portion of the total beta subunit in the heart, slight changes in this
      fraction are not detectable using Western analysis. In contrast, beta1 and beta3
      in skeletal muscle and brain, the predominant isoforms in these tissues,
      respectively, are membrane bound.

PMID- 12054672
TI  - Dissection of promoter control modules that direct Bmp4 expression in the
      epithelium-derived components of hair follicles.
AB  - Bone morphogenetic protein 4 (Bmp4) plays a significant role in development.
      Using transgenic approaches, we studied the mechanisms controlling Bmp4
      expression during primordial and mature tissue development, as well as in
      epithelium- and mesenchyme-derived components with hair follicles as a model. In
      this report, we demonstrated that the promoter region between the -0.26 and the 
      1.14 kb, highly conserved between human and mouse, controls Bmp4 expression in
      the epithelium-derived tissues but not in mesenchyme-derived tissues of hair
      follicles, suggesting that control modules for Bmp4 expression in epithelium
      derived tissues and mesenchyme originated tissues are in separate regions. Using
      live embryos and mice, we demonstrated the temporal and spatial activities of
      these modules. We also demonstrated that control regions for Bmp4 expression in
      primordial and differentiated hair follicle tissues are separated. Therefore we
      present a model to explain a mechanism controlling expression of the Bmp4 gene in
      different tissue types, as well as different development stages as related to
      hair development.

PMID- 12054673
TI  - Differentiation of liver epithelial (stem-like) cells into hepatocytes induced by
      coculture with hepatic stellate cells.
AB  - The liver is believed to contain stem cells that can differentiate into either
      hepatocytes or biliary epithelial cells. In the present study, we established a
      nonhepatocytic epithelial cell line from the normal livers of adult rats. The
      established cells, designated HSL cells, were immunoreactive against alpha
      fetoprotein, but neither albumin nor cytokeratin 19. To demonstrate the
      differentiation potential of HSL cells in vitro, the cells were cocultured with
      hepatic stellate cells as a mixture or separately using insert wells.
      Consequently, although coculture with hepatic stellate cells rendered HSL cells
      able to produce albumin, the mixed coculture system mimicking the hepatic
      environment elicited this phenomenon more effectively than the separated
      coculture system. In conclusion, HSL cells have immature properties and the
      potential to differentiate into mature cells. Not only the extracellular matrices
      but also soluble factors, which are produced by hepatic stellate cells, induce
      this maturation, demonstrating the importance of the hepatic environment for
      hepatocyte differentiation.

PMID- 12054674
TI  - Identification and genetic analysis of human and mouse activated Cdc42
      interacting protein-4 isoforms.
AB  - By yeast two-hybrid screening with the Src kinase Lyn as bait, we identified a
      novel gene product with features of a scaffolding protein. Reported as Felic ( es
      related, with homology to Ezrin, Lyn interactor with Cdc42), it is related to the
      CIP4 (Cdc42 Interacting Protein-4) gene. Southern blotting for CIP4/Felic of
      genomic DNA shows a single band, suggesting no gene duplication. Felic differs
      from CIP4 because of a 29 nucleotide sequence derived from the end of intron 13.
      Consequently, there is an out-of-frame translation that destroys an SH3 domain.
      Analysis of various tissues shows that the original CIP4 is the predominant
      transcript. Therefore, we propose to call that, CIP4a and Felic, CIP4b. During
      screening of the colorectal CaCo2 cell line, clones corresponding to a third CIP4
      related transcript (CIP4c) were identified. CIP4c encodes a premature stop codon,
      resulting in the loss of the SH3 domain. A fourth, relatively abundant transcript
      (CIP4h) was isolated from heart, lung, and trachea tissue. CIP4h retains the SH3
      domain. CIP4 levels are modified by all-trans-retinoic acid. The presence of
      alternative splice transcripts, with or without SH3 domains, suggests that CIP4
      regulates cytoskeletal organization through structural-functional differences in
      a tissue-specific manner.

PMID- 12054675
TI  - PPAR activators inhibit endothelial cell migration by targeting Akt.
AB  - Peroxisome proliferator-activated receptors (PPARs) regulate lipid and glucose
      metabolism and exert several vascular effects that may provide a dual benefit of
      these receptors on metabolic disorders and atherosclerotic vascular disease.
      Endothelial cell migration is a key event in the pathogenesis of atherosclerosis.
      We therefore investigated the effects of lipid-lowering PPARalpha-activators
      (fenofibrate, WY14643) and antidiabetic PPARgamma-activators (troglitazone,
      ciglitazone) on this endothelial cell function. Both PPARalpha- and PPARgamma
      activators significantly inhibited VEGF-induced migration of human umbilical vein
      endothelial cells (EC) in a concentration-dependent manner. Chemotactic signaling
      in EC is known to require activation of two signaling pathways: the
      phosphatidylinositol-3-kinase (PI3K)-->Akt- and the ERK1/2 mitogen-activated
      protein kinase (ERK MAPK) pathway. Using the pharmacological PI3K-inhibitor
      wortmannin and the ERK MAPK-pathway inhibitor PD98059, we observed a complete
      inhibition of VEGF-induced EC migration. VEGF-induced Akt phosphorylation was
      significantly inhibited by both PPARalpha- and gamma-activators. In contrast,
      VEGF-stimulated ERK MAPK-activation was not affected by any of the PPAR
      activators, indicating that they inhibit migration either downstream of ERK MAPK
      or independent from this pathway. These results provide first evidence for the
      antimigratory effects of PPAR-activators in EC. By inhibiting EC migration PPAR
      activators may protect the vasculature from pathological alterations associated
      with metabolic disorders.

PMID- 12054677
TI  - Functional GABA(B) receptors expressed in cultured calvarial osteoblasts.
AB  - In immature and mature primary cultured rat calvarial osteoblasts, both mRNA and
      corresponding proteins were constitutively expressed for 2 splice variants of
      GABA(B) receptor (GABA(B)R) subunits but not for any known GABA(A) and GABA(C)
      receptor subunits. The agonist for GABA(B)R baclofen significantly inhibited cAMP
      formation induced by forskolin in a manner sensitive to the antagonist 2
      hydroxysaclofen. Similar expression was seen with mRNA for GABA(B)R-1a and -1b
      splice variants in the murine calvarial osteoblast cell line MC3TC-E1 cells
      cultured for 7-21 days in vitro (DIV). In these MC3T3-E1 cells, baclofen not only
      inhibited the activity of alkaline phosphatase, but also exacerbated Ca2+
      accumulation, throughout the culture period up to 28 DIV. These results suggest
      that GABA may play an unidentified role in mechanisms associated with cellular
      proliferation, differentiation, and/or development through functional GABA(B)R
      constitutively expressed in cultured osteoblasts.

PMID- 12054676
TI  - Inhibition of cGMP-dependent protein kinase II by its own splice isoform.
AB  - cGMP- and cAMP-dependent protein kinases (cGK I, cGK II, and cAK) are important
      mediators of many signaling pathways that increase cyclic nucleotide
      concentrations and ultimately phosphorylation of substrates vital to cellular
      functions. Here we demonstrate a novel mRNA splice isoform of cGK II arising from
      alternative 5' splicing within exon 11. The novel splice variant encodes a
      protein (cGK II Delta(441-469)) lacking 29 amino acids of the cGK II Mg-ATP
      binding/catalytic domain, including the conserved glycine-rich loop consensus
      motif Gly-x-Gly-x-x-Gly-x-Val which interacts with ATP in the protein kinase
      family of enzymes. cGK II Delta(441-469) has no intrinsic enzymatic activity
      itself, however, it antagonizes cGK II and cGK I, but not cAK. Thus, the
      activation and cellular functions of cGK II may be determined not only by
      intracellular cGMP levels but also by alternative splicing which may regulate the
      balance of expression of cGK II versus its own inhibitor, cGK II Delta(441-469).

PMID- 12054678
TI  - Histone cross-linking by transglutaminase.
AB  - Transglutaminases irreversibly catalyze covalent cross-linking of proteins by
      forming isopeptide bonds between peptide-bound glutamine and lysine residues.
      Among several transglutaminases, tissue-type transglutaminase (tTGase) is most
      ubiquitously found in every type of cells and tissues in animals, but its natural
      substrate has yet to be identified. In an attempt to identify the natural
      substrate for tTGase, we examined in vitro if core histones were subject to cross
      linking by tTGase. We found core histone subunits, H2A and H2B, were specifically
      cross-linked by tTGase. The cross-linking was between either one or both
      glutamines at C-terminal end of H2A (-VTIAQ104 GGVLPNTQ112 SVLLPKKTESSKSK-C' end)
      and the first and/or third lysine from C-terminal end of H2B (-AVESEGK116
      AVTKYTSSK125-C' end). The cross-linking occurred only when these subunits were
      released from nucleosome but not when these were organized in nucleosome. Most
      interestingly, in chicken erythrocyte the cross-linked H2A-H2B was present in a
      significant amount. From these results, it can be proposed that tTGase-mediated
      cross-linking is an another form of core histone modification and it may play a
      role of chromatin condensation during erythrocyte differentiation.

PMID- 12054680
TI  - Oscillatory shear alters endothelial hydraulic conductivity and nitric oxide
      levels.
AB  - This study addresses the role of nitric oxide (NO) and downstream signaling
      pathways in mediating the influences of oscillatory shear stress on the hydraulic
      conductivity (L(p)) of bovine aortic endothelial cell (BAEC) monolayers. Exposure
      of BAEC monolayers to 20 dyne/cm2 steady shear stress for 3 h induced a 3.3-fold
      increase in L(p). When an oscillatory shear amplitude of 10 dyne/cm2 was
      superimposed on a steady shear of 10 dyne/cm2 to produce a non-reversing
      oscillatory shear pattern (10+/-10 dyne/cm2), L(p) increased by 3.0-fold within
      90 min. When the amplitude was increased to 15 dyne/cm2, resulting in a reversing
      oscillatory shear pattern (10+/-15 dyne/cm2), the increase in L(p) over 3 h was
      completely suppressed. Twenty and 10+/-10 dyne/cm2 induced 2.9- and 2.6-fold
      increases in NO production above non-sheared controls, respectively, whereas 10+/
      15 dyne/cm2 stimulated a 14-fold increase in NO production. The inhibition of
      L(p) with reversing oscillatory shear may be associated with alterations in
      cyclic guanosine monophosphate (cGMP) production downstream of NO which is up
      regulated by reversing oscillatory shear, but is unaffected by steady shear.

PMID- 12054679
TI  - Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the
      inhibition of JNK and AP-1 signaling pathway.
AB  - We previously reported that quercetin, a bioflavonoid belonging to polyphenols,
      inhibited Angiotensin II (Ang II)-induced vascular smooth muscle cell (VSMC)
      hypertrophy through the inhibition of c-Jun N-terminal kinase (JNK) activation.
      However, we recently found that orally administered quercetin appeared in plasma
      as glucuronide-conjugated forms in rats and humans. Therefore we examined the
      effect of chemically synthesized quercetin glucuronide on Ang II-induced mitogen
      activated protein (MAP) kinase activation and hypertrophy of cultured rat aortic
      smooth muscle cells (RASMC). Ang II activated extracellular signal-regulated
      kinase (ERK)1/2, JNK, and p38 in RASMC. Ang II-induced JNK activation was
      inhibited by quercetin 3-O-beta-d-glucuronide (Q3GA) whereas ERK1/2 and p38
      activations were not affected. Q3GA scavenged 1,1-diphenyl-2-picrylhydrazyl
      radical measured by a method of electron paramagnetic resonance. Q3GA also
      inhibited Ang II-induced increases in activator protein-1 (AP-1) DNA binding, a
      downstream transcription factor of JNK. Finally, Ang II-induced [3H]leucine
      incorporation into RASMC was abolished by Q3GA. These findings suggest that the
      preventing effect of Q3GA on Ang II-induced VSMC hypertrophy is attributable in
      part to its inhibitory effect on JNK and the AP-1 signaling pathway. Q3GA would
      be an active metabolite of quercetin in plasma and may possess a preventing
      effect for cardiovascular diseases relevant to VSMC growth.

PMID- 12054681
TI  - Identification and characterization of murine IRAK-M.
AB  - Interleukin-1 receptor-associated-kinases (IRAKs) are signal transduction
      mediators of the Toll/IL-1 receptor family, which comprise several transmembrane
      proteins involved in host defense mechanisms. Today four different human IRAKs
      (hu-IRAK-1, hu-IRAK-2, hu-IRAK-M, hu-IRAK-4) and two murine IRAKs (mouse pelle
      like kinase (mPLK) and mu-IRAK-4) have been described. Here we report the
      identification and characterization of murine IRAK-M (mu-IRAK-M), a mouse
      homologue to human IRAK-M (hu-IRAK-M). These IRAK-M molecules show 71% sequence
      identity, a comparable cellular expression, and functional similarities with
      respect to signal transduction capacity and kinase activity, suggesting
      functional homology in signalling in human and mouse cells.

PMID- 12054682
TI  - Cytotoxic activity of 2',2'-difluorodeoxycytidine, 5-aza-2'-deoxycytidine and
      cytosine arabinoside in cells transduced with deoxycytidine kinase gene.
AB  - Deoxycytidine nucleoside analogs must be first phosphorylated to become active
      anticancer drugs. The rate-limiting enzyme in this pathway is deoxycytidine
      kinase (dCK). Cells deficient in this enzyme are resistant to these analogs. To
      evaluate the potential of dCK to be used as suicide gene for deoxycytidine
      nucleoside analogs, we transduced both human A-549 lung carcinoma and murine
      NIH3T3 fibroblast cell lines with this gene. The dCK-transduced cells showed an
      increase in cytotoxicity to the analogs, cytosine arabinoside (ARA-C), and 5-aza
      2'-deoxycytidine (5-AZA-CdR). Unexpectedly, the related analog, 2',2'
      difluorodeoxycytidine (dFdC), was less cytotoxic to the dCK-transduced cells than
      the wild-type cells. For the A-549-dCK cells, the phosphorylation of dFdC by dCK
      was much greater than control cells. In accord with the elevated enzyme activity,
      we observed a 6-fold increased dFdC incorporation into DNA and a more pronounced
      inhibition of DNA synthesis in the A-549-dCK cells. In an attempt to clarify the
      mechanism of dFdC, we investigated its action on A549 and 3T3 cells transduced
      with both cytidine deaminase (CD) and dCK. We reported previously that
      overexpression of CD confers drug resistance to deoxycytidine analogs. In this
      study, when the CD-transduced cells were also transduced with dCK they became
      relatively more sensitive to dFdC. In addition, we observed that dFdU, the
      deaminated form of dFdC, was cytotoxic to the A-549-dCK cells, but not the wild
      type cells. Our working hypothesis to explain these results is that the
      mitochondrial thymidine kinase (TK2), an enzyme reported to phosphorylate dFdC,
      acts as an important modulator of dFdC-induced cell toxicity. These findings may
      further clarify the action of dFdC and the mechanism by which it induces cell
      death.

PMID- 12054683
TI  - Brain hydrogen sulfide is severely decreased in Alzheimer's disease.
AB  - Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous
      gas, it is endogenously produced in the brain from cysteine by cystathionine beta
      synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle
      relaxant. Here we show that the levels of H2S are severely decreased in the
      brains of Alzheimer's disease (AD) patients compared with the brains of the age
      matched normal individuals. In addition to H2S production CBS also catalyzes
      another metabolic pathway in which cystathionine is produced from the substrate
      homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM),
      a CBS activator, is much reduced in AD brain and that homocysteine accumulates in
      the serum of AD patients, were confirmed. These observations suggest that CBS
      activity is reduced in AD brains and the decrease in H2S may be involved in some
      aspects of the cognitive decline in AD.

PMID- 12054684
TI  - Low level of mitochondrial deoxyguanosine kinase is the dominant factor in
      acquired resistance to 9-beta-D-arabinofuranosylguanine cytotoxicity.
AB  - 9-beta-D-arabinofuranosylguanine (Ara-G) is an important and relatively new
      guanosiue analog with activity in patients with T-cell malignancies. The
      biochemical and molecular events leading to resistance to Ara-G are not fully
      understood. Therefore we generated two Ara-G-resistant human MOLT-4 leukemic cell
      lines with different levels of resistance. The mitochondrial enzyme
      deoxyguanosine kinase (dGK) and the nuclear/cytosol enzyme deoxycytidine kinase
      (dCK) are key enzymes in the activation of Ara-G. Decreased levels of dGK protein
      and mRNA were found in both resistant cell sublines. The activity of dCK was
      decreased in the subline with higher resistance to Ara-G and these cells were
      highly cross-resistant to other nucleosides activated by dCK. Increased activity
      of the mitochondrial enzyme thymidine kinase 2 was observed in both resistant
      sublines and this could be related to the dGK deficiency. In search for other
      resistance mechanisms it was found that the resistant cells overexpress the mdr1
      gene, while no changes were detected in the levels of multidrug resistance
      associated protein 1 through 6, lung resistance-associated protein or
      topoisomerase IIalpha or IIbeta. Taken together, our findings demonstrate that
      multiple mechanisms are involved in the acquired resistance to Ara-G. However,
      low expression of dGK is the most apparent alteration in both resistant cell
      lines. Partial deficiency of dCK was found in the subline cells with higher
      resistance to Ara-G. Furthermore, Ara-G may select for high expression of the
      multidrug resistance (mdr1) which could be a specific resistance mechanism but
      more likely part of an overall cellular stress response.

PMID- 12054685
TI  - The proteolytic release of genotoxins from cooked beef.
AB  - Dietary factors are important in the aetiology of human cancer and carcinogens,
      mostly heterocyclic aromatic amines, have been isolated from cooked proteinaceous
      foodstuffs. Whilst such carcinogens have induced tumours in rodent bioassays, the
      dosages required were much higher than estimates of human exposure levels. We
      have examined the possibility that genotoxins, which were not extractable prior
      to enzymic digestion, may be released from cooked beef by proteolysis.
      Dichloromethane and/or a solid-phase tandem extraction procedure were used with
      aqueous homogenates of pan-fried or uncooked beef, both before and after
      proteolysis (proteinase K). Genotoxicity was measured using the alkaline single
      cell-gel electrophoresis ('Comet') assay in MCL-5 cells and mutagenicity in
      Salmonella typhimurium strains TA1538 or YG1019. Proteolysis released significant
      amounts of DNA-damaging material that was not extractible prior to enzymic
      digestion, suggesting that human exposures to diet-derived genotoxins may have
      been underestimated.

PMID- 12054686
TI  - Cytotoxic and cytostatic effects induced by 4-hydroxynonenal in human
      osteosarcoma cells.
AB  - Several studies point to the existence of an inverse correlation between cellular
      lipid peroxidation and both cell proliferation and neoplastic transformation.
      Furthermore, numerous results demonstrate that lipid peroxidation products affect
      central biochemical pathways and intracellular signalling at physiological
      concentrations. 4-Hydroxynonenal (HNE) is one of the most active products of
      lipid peroxidation. This work has focused on the evaluation of HNE nuclear
      content, so far never directly measured, by electrospray-ionization-mass
      spectrometry (ESI/MS) and on the correlation between its concentration and the
      induced effects after exogenous administration. In a human osteosarcoma cell line
      (SaOS2), HNE exhibited an early cytotoxic effect characterized by apoptosis,
      cytostatic and differentiating effects characterized by slow growth, increase in
      alkaline phosphatase (ALP), and alpha5 integrin subunit content with decrease in
      tumorigenicity.

PMID- 12054687
TI  - The catalytic subunits of IkappaB kinase, IKK-1 and IKK-2, contain non-equivalent
      active sites when expressed as homodimers.
AB  - The signal-inducible phosphorylation of serines 32 and 36 of IkappaBalpha is the
      key step in regulating the subsequent ubiquitination and proteolysis of
      IkappaBalpha which then releases NF-kappaB to promote gene transcription. The
      multisubunit IkappaB kinase responsible for this phosphorylation contains two
      catalytic subunits, termed IKK-1 and IKK-2. It has been shown that both subunits
      catalyze the phosphorylation of IkappaBalpha as well as an autophosphorylation at
      a C-terminal cluster of serines. With baculovirus/insect cell-expressed
      homodimeric IKK-1 or IKK-2, inhibitors such as ADP or a peptide inhibitor
      (corresponding to amino acid residues 26-42 of IkappaBalpha with Ser-32 and Ser
      36 changed to aspartates) inhibited autophosphorylation and IkappaBalpha
      phosphorylation reactions with different potencies. ADP was more potent against
      IkappaBalpha phosphorylation as compared to autophosphorylation, while the
      peptide inhibitor showed the opposite effect. Pseudo-Dixon plots of the
      inhibition with ADP were linear while non-linear plots were obtained with the
      peptide inhibitor, suggesting a cooperative effect in the case of the latter.
      Using different concentrations of IKK-1, autophosphorylation was shown to be
      intramolecular. These results indicated that there were non-equivalent active
      sites present within the preparations of recombinant homodimers of IKK-1 and IKK
      2. The peptide inhibitor showed equivalent inhibitory effects with wild-type IKK
      1 and the S176E/S180E mutant. In contrast, ADP showed equipotent inhibition
      against the S176E/S180E mutant-catalyzed autophosphorylation and IkappaBalpha
      phosphorylation reactions. A model is proposed in which the phosphorylation state
      of the activation loop of IKK-1 or IKK-2 affects the active site conformation of
      the enzyme such that the two forms catalyze the autophosphorylation and
      IkappaBalpha phosphorylation reactions with different affinities. In addition,
      the two active sites within the dimer appear to act in a cooperative fashion so
      that binding of peptide inhibitor at one active site affects the conformation of
      the other active site.

PMID- 12054688
TI  - Purification, structure-function analysis, and molecular characterization of
      novel linear peptides from scorpion Opisthacanthus madagascariensis.
AB  - In the previous report [Biochem. Biophys. Res. Commun. 286 (2001) 820], we
      described a novel short linear peptide, IsCT, with cytolytic activity isolated
      from the venom of scorpion Opisthacanthus madagascariensis. From the same
      scorpion venom, we further purified and characterized three short linear peptides
      named IsCT2, IsCTf, and IsCT2f that shared high homology with IsCT, while with
      different C-terminal areas between IsCT/IsCT2 and IsCTf/IsCT2f. Structure
      activity relationship was analyzed by performing vivo and vitro assays and
      circular dichroism spectroscopy. Like IsCT, IsCT2 showed broad activity spectra
      against microbes (Gram positive and negative bacteria as well as fungi) and
      relatively weak hemolytic activity against sheep red blood cells. It adopts an
      amphipathic alpha-helical structure in aqueous TFE and is able to disrupt the
      artificial membrane. However, the other two peptides IsCTf and IsCT2f showed no
      activity in antimicrobial or hemolytic assay. Furthermore, IsCTf and IsCT2f
      cannot form amphipathic alpha-helix while demonstrating random coil structure in
      aqueous TFE, which might result in their lost cytolytic activity. IsCTf and
      IsCT2f both exist in the crude venom and are proved to be enzymatic products from
      IsCT and IsCT2. Whether they have some other biological activity is still
      unclear. In addition, we got the cDNAs encoding the precursors of IsCT and IsCT2.
      Besides the signal peptide, they still contain an unusual acidic pro-peptide at
      the C-terminal that was quite different from other known precursors of scorpion
      venom peptides. The novel structure and biological activity of these peptides
      proposed them to be a new class in scorpion venom.

PMID- 12054689
TI  - A novel pex2 mutant: catalase-deficient but temperature-sensitive PTS1 and PTS2
      import.
AB  - We searched for Chinese hamster ovary (CHO) cell mutants defective in peroxisome
      biogenesis by using peroxisome targeting sequence (PTS) of Pex3p (amino acid
      residues 1-40)-fused enhanced green fluorescent protein (EGFP). From mutagenized
      wild-type CHO-K1 cells stably expressing rat Pex2p and Pex3p(1-40)-EGFP, cell
      colonies resistant to the 9-(1(')-pyrene)nonanol/ultraviolet treatment were
      examined for intracellular location of peroxisomal proteins, including EGFP
      chimera, catalase, and matrix proteins with PTS types 1 and 2. One clone,
      ZPEG309, showed a distinct phenotype: import defect of catalase, but normal
      transport of PTS1 and PTS2 proteins at 37 degrees C. PTS1 and PTS2 import was
      abrogated when ZPEG309 was cultured at 39 degrees C. Genetic defect of ZPEG309
      was a nonsense point mutation in a codon for Arg50 in CHO PEX2 and a mutation
      resulting in a C-terminal truncation of the introduced rat Pex2p. Therefore,
      ZPEG309 is a novel pex2, catalase-deficient mutant with temperature-sensitive
      PTS1 and PTS2 import.

PMID- 12054690
TI  - Successful genetic transduction in vivo into synovium by means of
      electroporation.
AB  - This present study aims at establishing a novel in vivo gene delivery system for
      intra-articular tissues. Plasmid DNA (pDNA) carrying the firefly luciferase or
      enhanced green fluorescent protein (EGFP) genes as markers was injected into a
      joint space and electric stimuli were given percutaneously with a pair of
      electrodes. Injection with naked pDNA alone did not induce any detectable level
      of luciferase activity, whereas electroporation at 25-500 V/0.7 cm resulted in a
      significant expression of the marker gene in the synovium. The expression level
      depended on the voltage, the optimum transfection being achieved at 150 V/0.7 cm.
      When the Epstein-Barr virus (EBV)-based plasmid vectors harboring the EBV nuclear
      antigen 1 (EBNA1) gene and oriP sequence were substituted for conventional pDNA,
      the transfection efficiency was increased approximately 5-10 times. Histological
      examination of the EGFP gene-transfected joints revealed that the marker gene was
      expressed in the synovial membrane while other intra-articular tissues such as
      articular cartilage were negative for the transgene product. Transgene-specific
      mRNA was demonstrated in synovium but not in other organs as estimated by RT-PCR
      analysis. The present results strongly suggest that in vivo electroporation is a
      quite simple, safe, and effective gene delivery method that could be applicable
      to gene therapy against articular diseases.

PMID- 12054691
TI  - NMDA receptor stimulation induces temporary alpha-tubulin degradation signaled by
      nitric oxide-mediated tyrosine nitration in the nervous system of Sepia
      officinalis.
AB  - Biochemical and immunohistochemical evidence is reported, showing basal protein
      nitration in specific regions of the optic lobes of Sepia officinalis, mainly in
      the fiber layers of the plexiform zone. SDS-PAGE analysis of optic lobe extracts
      revealed an intense 3-nitrotyrosine immunoreactive band identified as alpha
      tubulin by immunoprecipitation and partial purification. Stimulation of NMDA
      receptors resulted in a selective decrease in alpha-tubulin levels within 30 min
      with partial recovery after 4 h. The effect was suppressed by the NO synthase
      (NOS) inhibitor L-nitroarginine. Incubation of optic lobes with free 3
      nitrotyrosine resulted likewise in a selective loss of alpha-tubulin, due
      apparently to incorporation of the amino acid into the C-terminus of
      detyrosinated alpha-tubulin to give the nitrated protein purportedly more
      susceptible to degradation. Overall, these results point to a novel potential
      physiologic role of NO and free 3-nitrotyrosine in the control of the alpha
      tubulin tyrosination/detyrosination cycle and turnover in Sepia nervous tissue.

PMID- 12054692
TI  - RCAS1 is associated with ductal breast cancer progression.
AB  - RCAS1/EBAG9 (receptor-binding cancer antigen expressed on SiSo cells/ estrogen
      receptor-binding fragment-associated gene 9), an estrogen-transcribed protein,
      has been shown to be expressed in a wide variety of cancers, including uterine,
      ovarian, and lung cancer cells. Soluble and membranous RCAS1 proteins may play a
      role in the immune escape of tumor cells by promoting T lymphocyte inhibition of
      growth and apoptosis. In the present report, the presence of RCAS1 was revealed
      in human ductal breast cancer biopsies by immunohistochemistry. Its cytoplasmic
      expression was exhibited in cancer cells obtained from tumor biopsies and in
      breast cancer cell lines. RCAS1 significantly correlated with tumor grade. In
      addition, RCAS1 was identified in MCF7 culture supernatants. Those observations
      suggest that RCAS1 is a new marker for breast cancer progression and a possible
      mechanism for breast cancer immune escape.

PMID- 12054693
TI  - Visualization and force measurement of branching by Arp2/3 complex and N-WASP in
      actin filament.
AB  - To determine whether the Arp2/3 complex activated by N-WASP (VCA) branches actin
      filaments at the side (side branching), or at the barbed (B-)end (end branching)
      of the mother filaments, we have directly observed the branching process of actin
      filaments and examined single-molecule unbinding under optical microscope. We
      found that side branching was predominant, though not exclusive. At the initial
      stage of polymerization, the branching at the B-end occurred and subsequently the
      side branching started to occur. In either type of branching, the mother and
      daughter filaments elongated at nearly the same rate (growing type).
      Independently of the stage of polymerization, branching due to the direct
      coupling of filaments with an acute angle to the mother filaments (a coupling
      type) occurred. Phalloidin suppressed the growing type of branching but not the
      coupling type, implying that actin monomers are required for the former but not
      the latter. We found, by single molecule measurements using optical tweezers,
      that the Arp2/3 complex attaches to the side of actin filaments and the N-WASP
      appears to detach from the actin-Arp2/3 complex at 6-7 pN.

PMID- 12054695
TI  - Identification of oxidized plasma proteins in Alzheimer's disease.
AB  - The modification of proteins by reactive oxygen species is central to the
      pathology of Alzheimer's disease (AD). Previously, we have observed specific
      oxidized proteins in blood plasma of AD subjects [Biochem. Biophys. Res. Commun.
      275 (2000) 678]. Plasma from AD subjects and age-matched controls was subjected
      to two-dimensional gel electrophoresis (2-DE). Oxidized proteins with new
      carbonyl groups were detected by reaction with 2,4-dinitrophenylhydrazine,
      followed by Western blotting with anti-DNP antibody. Seven principal oxidized
      protein spots (isoelectric point=4.7-5.5; molecular mass=45-65 kDa) were
      observed, with varying levels of oxidation in plasma samples from both AD and non
      AD subjects. Matrix-assisted laser desorption mass spectroscopy (MALDI-TOF/MS)
      revealed that these oxidized proteins were isoforms of fibrinogen gamma-chain
      precursor protein and of alpha-1-antitrypsin precursor. These proteins exhibited
      a two- to sixfold greater specific oxidation index in plasma from AD subjects
      when compared to controls. Both these proteins have been previously implicated in
      the pathology of the disease. It is possible that oxidized isoforms of these
      proteins may serve as biomarkers for AD.

PMID- 12054694
TI  - The novel type I serine-threonine kinase receptor Alk8 binds TGF-beta in the
      presence of TGF-betaRII.
AB  - The TGF-beta superfamily consists of an array of ligands including BMP, TGF-beta,
      activin, and nodal subfamilies. The extensive range of biological effects
      elicited by TGF-beta family signaling is due in part to the large numbers and
      promiscuity of types I and II TGF-beta family member receptors. Alk8 is a novel
      type I TGF-beta family member receptor first identified in zebrafish [Dev. Dyn.
      211 (4) (1998) 352], which participates in BMP signaling pathways [Development
      128 (6) (2001) 849; Development 128 (6) (2001) 859; Mech. Dev. 100 (2) (2001)
      275; J. Dent. Res. 80 (11) (2001) 1968]. Here we report that Alk8 also forms
      active signaling complexes with TGF-beta in the presence of TGF-betaRII. These
      results expand the signaling repertoire of zAlk8 by demonstrating an ability to
      participate in two distinct TGF-beta subfamily signaling pathways.

PMID- 12054696
TI  - Relationship between p38 mitogen-activated protein kinase and small GTPase Rac
      for the activation of NADPH oxidase in bovine neutrophils.
AB  - Superoxide production by NADPH oxidase is essential for bactericidal properties
      of neutrophils. However, molecular mechanisms underlying the activation of this
      enzyme remain largely unknown. Here, using bovine neutrophils we examined the
      role of p38 mitogen-activated protein kinase (p38 MAPK) in the signaling pathways
      of the NADPH oxidase activation. Superoxide production was induced by stimulation
      with serum-opsonized zymosan (OZ) and attenuated by p38 MAPK inhibitor, SB203580.
      OZ stimulation induced the translocation of p47(phox) and Rac to the plasma
      membrane and SB203580 completely blocked the translocation of Rac, but only
      partially blocked that of p47(phox). Furthermore, SB203580 abolished the OZ
      elicited activation of Rac, which was assessed by detecting the GTP-bound form of
      this protein. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and
      LY294002, blocked not only p38 MAPK activation but also Rac activation. However,
      SB203580 showed no effect on the PI3K activity. These results suggested that
      PI3K/p38 MAPK/Rac pathway was present in the activation of NADPH oxidase in
      bovine neutrophils.

PMID- 12054697
TI  - Trypanosoma cruzi: isoenzyme analysis suggests the presence of an active Chagas
      sylvatic cycle of recent origin in Parana State, Brazil.
AB  - Thirty-one trypanosomatid stocks were isolated from various sylvatic hosts and
      vectors in two different regions from the Parana State of Brazil. The stocks were
      analyzed by multilocus enzyme electrophoresis (MLEE) on cellulose acetate plates
      (22 genetic loci). All stocks were unambiguously attributed to Trypanosoma cruzi,
      and were found to be closely related to the formerly described zymodeme I (TC1
      subgroup of T. cruzi). By comparison with other sylvatic cycles with similar
      sample sizes (Southern USA, Colombia, French Guiana), genetic variability among
      these stocks was very limited, with only two variable loci out of 22, and only
      three different multilocus genotypes. Population structure of T. cruzi in these
      cycles appears to correspond to a set of very closely related clonal genotypes.
      This very limited genetic variability could be due to a recent foundation of
      these populations (founder effect). The implications of an active Chagas sylvatic
      cycle in this area are discussed.

PMID- 12054698
TI  - Taenia solium: identification of specific antibody binding regions of metacestode
      10-kDa protein.
AB  - Taenia solium neurocysticercosis (NCC) represents one of the major public health
      problems associated with several neurological manifestations worldwide. We
      previously identified a recombinant 10-kDa protein of T. solium metacestode
      (CyDA) specific to active NCC. Immunoblottings with sera from active NCC patients
      and from animals experimentally infected with larval T. solium (pig), T. saginata
      (pig), T. asiatica (pig), and T. crassiceps (mouse) strongly recognized CyDA,
      while sera from patients infected only with adult worms did not. Mapping of
      antigenic sites using deletion mutants revealed that amino acids (aa) residues 30
      34, Asn-Met-Thr-Val-Met (NMTVM), reacted only with sera from active stage T.
      solium cysticercosis cases. Recognition of CyDA aa 30-34 resided almost
      exclusively in the IgG4 isotype. Competitive immunoprecipitation with synthetic
      peptides confirmed the specificity of anti-sera for this penta-peptide. These
      results demonstrated that aa residues NMTVM in CyDA comprise the core sequence
      for an active stage NCC-related antigenic determinant. ligand binding protein,
      HLBP; Cyst fluid, CF; Pooled serum of 10 active NCC patients, serum-pool.

PMID- 12054699
TI  - Brugia malayi: transient transfection by microinjection and particle bombardment.
AB  - To develop a method for the introduction of DNA into filarial parasites, several
      methods that have proven successful in other organisms were evaluated for their
      ability to transform Brugia malayi. Luciferase activity was detectable in embryos
      bombarded with gold particles coated with a construct consisting of a luciferase
      reporter gene under the control of the 5S rRNA intergenic spacer (SL promoter).
      Similar results were seen in adult parasites and infective larvae bombarded with
      this construct, or in adult female parasites microinjected with the plasmid. In
      similar experiments employing the SL promoter driving a green fluorescent protein
      (GFP) reporter, expression of the reporter was detectable in the intrauterine
      embryos of the microinjected adult parasites, and in the sub-cuticular tissues of
      biolistically transfected adult female parasites. A similar pattern of GFP
      expression to that seen in the SL promoter construct transfected parasites was
      noted in parasites transfected with constructs consisting of the upstream domain
      derived from an aspartyl aminoacyl tRNA synthetase gene of B. malayi. The ability
      to transfect B. malayi embryos may provide a foundation for studies of the
      regulation of gene expression and function in these organisms.

PMID- 12054700
TI  - Pancreatic hepatocytes in hamsters (Mesocricetus auratus) infected with
      Trypanosoma cruzi.
AB  - Hepatocytic metaplasia may be induced in hamsters by carcinogens, and associated
      with aging, diabetes or chronic pancreatitis. By means of histopathologic and
      immunohistochemic studies, we observed pancreatic hepatocytes in hamsters
      infected and reinfected with Trypanosoma cruzi. The change was seen in 18 (19%)
      out of 94 infected animals, and was not found among 53 controls, Normal islet
      cells were immunoreactive for neuron-specific enolase and not reactive for NCL
      HAS. Metaplastic cells were immunoreactive for NCL-HAS and not reactive for islet
      hormones and enolase. No relationship was observed between number of inoculations
      and metaplasia; however, the intensity of the inflammatory process and sequels
      seems to favor the development of metaplastic cells. Hamsters infected with T.
      cruzi may be useful to study hepatocytic metaplasia, and contribute to clarify
      aspects of Chagas' disease and pancreatic changes. Our data indicate that aging,
      in addition to inflammation and atrophy, plays a role in this change.

PMID- 12054701
TI  - Immunoaffinity-isolated antigens induce protective immunity against larval
      Strongyloides stercoralis in mice.
AB  - The objective of this study was to identify soluble protein antigens that would
      induce protective immunity against infective-stage larvae (L-3) of Strongyloides
      stercoralis in mice. Deoxycholate (DOC)-soluble proteins derived from L-3,
      adsorbed to aluminum hydroxide, induced protective immunity in BALB/c mice. The
      immunized mice generated parasite-specific IgG that could transfer passive
      immunity to naive animals. The protective antibodies bound to parasite antigens
      found in the muscles and nerve cords of the L-3. An IgG affinity chromatography
      column generated with IgG from the sera of DOC-immunized mice was used to purify
      specific larval antigens. Proteins were eluted from the affinity column with
      sizes of 80, 75, 61, 57, 43, and 32 kDa. This antigen pool stimulated both
      proliferation and IL-5 production by splenocytes recovered from mice immunized
      with live L-3. Vaccination of mice with the immunoaffinity-isolated antigens led
      to significant protective immunity, with 83% of challenge larvae killed. This
      study demonstrates that IgG-isolated proteins are candidate antigens for a
      vaccine against larval S. stercoralis.

PMID- 12054702
TI  - Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s)
      interacts with human alpha(2)-macroglobulin and pregnancy zone protein.
AB  - Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute
      Chagas disease. PZP, as well as alpha2-macroglobulin (alpha2-M), are able to
      interact with Trypanosoma cruzi proteinases. The interaction of alpha2-M and PZP
      with cruzipain, the major cysteine proteinase of T. cruzi, was investigated.
      Several molecular changes on both alpha-M inhibitors under reaction with
      cruzipain were found. PAGE analysis showed: (i) formation of complexes of
      intermediate mobility and tetramerization of native alpha2-M and PZP,
      respectively; (ii) limited proteolysis of bait region in alpha2-M and PZP, and
      (iii) covalent binding of cruzipain to PZP and alpha2-M. Conformational and
      structural changes experimented by alpha-Ms correlate with modifications of the
      enzyme electrophoretic mobility and activity. Cruzipain-alpha-M complexes were
      also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti
      cruzipain antibodies. Concomitantly, alpha2-M and PZP impaired the activity of
      cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, alpha-Ms were able
      to form covalent complexes with membrane isoforms of cysteine proteinases cross
      reacting with cruzipain. The present study suggests that both human alpha
      macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on
      host's molecules and hypothetically regulate parasite functions controlled by
      cruzipain.

PMID- 12054703
TI  - Plasmodium vivax: parasitemia determination by real-time quantitative PCR in
      Aotus monkeys.
AB  - Plasmodium vivax and Plasmodium falciparum are the two prevalent human malaria
      species. A Colombian P. vivax wild strain has been adapted in Aotus nancymaae
      monkeys for use in further biological and immunological studies. We present data
      validating a real-time PCR assay quantifying P. vivax parasitemia, using the
      small subunit ribosomal RNA genes as an amplification target. P. vivax species
      specific primers were designed on the 18S ribosomal gene V8 region, for
      amplifying both asexual and sporozoite ssrRNA genes. The assay detects
      amplification products bound to fluorescent SYBR-Green I dye using Perkin-Elmer
      GeneAmp-5700-SDS. Linear range standard curves from 6 DNA concentration logs
      (+0.99 correlation coefficients) were obtained. Standard curves were constructed
      using a plasmid containing target gene for real-time PCR amplification. This P.
      vivax specific assay is very sensitive, having a three parasite detection limit,
      and is reproducible and accurate. It involves a "closed-tube" PCR, avoids time
      consuming post-PCR manipulation, and decreases potential PCR contamination.

PMID- 12054704
TI  - Entamoeba histolytica genomic organization: identification, structure, and
      phylogenetic relationship of two serine-threonine protein kinases.

PMID- 12054705
TI  - Mouse H2 haplotype influences on the survival rate after Angiostrongylus
      costaricensis infection.

PMID- 12054707
TI  - Expression of nitric oxide synthase-2 in cutaneous squamous cell carcinoma of the
      head and neck.
AB  - Nitric oxide (NO) has a pivotal role in angiogenesis. The expression of NO
      synthase (NOS2) is down-regulated in basal cell skin cancer but we know of no
      studies that have investigated its expression in the more aggressive squamous
      cell skin carcinoma. This immunohistochemical study assessed NOS2 expression in
      37 cases of head and neck squamous cell skin carcinoma. NOS2 expression was
      located in cells of the basal cell layer of epidermis, but was significantly
      increased in tumour epithelium. No correlations were found between NOS2
      expression and tumour size or degree of tumour differentiation. The raised NO
      concentrations in these tumours may provide one explanation for their more
      aggressive behaviour than that of the slower-growing basal cell carcinoma.

PMID- 12054706
TI  - Vascularized iliac crest with internal oblique muscle for immediate
      reconstruction after maxillectomy.
AB  - The vascularized iliac crest graft with internal oblique muscle as a method of
      reconstruction after maxillectomy has been used routinely at the Regional
      Maxillofacial Unit in Liverpool since 1993. Twenty-four consecutive operations
      have now been done and this paper reports an audit of our experience. An analysis
      of case-notes was made retrospectively after checking theatre diaries and
      records. A detailed inspection of the case-notes was undertaken to ascertain the
      presenting diagnosis, the complications and the outcome in terms of recurrence
      and disease survival. The type of defect was recorded, as was whether it had been
      possible to rehabilitate the patient both dentally and facially. At the time of
      this study 9 patients (38%) had died of their disease leaving 15 surviving. In 13
      cases full dental and facial rehabilitation had been achieved or patients were
      waiting for an implant-retained prosthesis. Donor site problems important enough
      to be recorded in the notes were minimal, one case of abdominal wall weakness was
      noted, which required no intervention. The vascularized iliac crest graft with
      internal oblique muscle offers a complete solution for reconstruction after
      maxillectomy, providing there has been no sacrifice of the overlying facial skin
      and oral sphincter. There is sufficient height and depth of bone to maintain a
      facial profile and the muscle epithelializes to provide an ideal oral and nasal
      lining. This flap provides a base to enable full dental and facial prosthetic
      rehabilitation with either implant-retained or conventional prostheses.

PMID- 12054708
TI  - Amelanotic malignant melanomas of the oral mucosa.
AB  - Oral amelanotic melanomas are rare and the prognosis is poorer than that of
      pigmented melanomas because of delays in establishing the correct diagnosis and
      in the initiation of treatment. Amelanotic forms are also thought to be
      biologically more aggressive than pigmented melanomas. We have seen three cases
      of oral amelanotic melanomas since 1970, in two of whom the diagnosis was long
      delayed. Two lesions were not pigmented but one had slight pigmentation. One
      patient simultaneously had both an amelanotic and a pigmented melanoma in the
      oral cavity. Lymph node metastases and distant metastases developed in all
      patients, two of whom eventually died of the disease. Early diagnosis by
      histological examination together with immunostaining with S100 and HMB-45 are
      the keys to improve survival for patients with amelanotic melanoma.

PMID- 12054710
TI  - Ultrastructural changes in malignant transformation of oral mucosa.
AB  - Transmission electron microscopy (EM) has been used to identify the
      ultrastructural details of normal and cancerous human oral mucosa. However,
      inconsistent reports of structural descriptions have rendered transmission EM
      valueless in the diagnosis of oral squamous cell carcinoma (SCC) or as a
      prognostic indicator. To identify features of dysplasia for diagnostic purposes,
      normal mucosa, severe dysplasia, oral SCC and normal margin adjacent to oral SCC
      were used to compare the ultrastructural features of normal and premalignant oral
      mucosa and oral SCC. The preparatory stages of dehydration, embedding, cutting
      and positive staining for transmission EM were modified and tested to improve
      ultrastructural definition. Thin and discontinuous basal laminas were found in
      mucosa with severe dysplasia and normal margin adjacent to oral SCC. No basal
      lamina was identified in oral SCC. This study has shown that there are some
      ultrastructural changes during malignant transformation of oral mucosa. Together
      with other laboratory investigative techniques, transmission EM may be helpful in
      detecting malignant changes in oral mucosa.

PMID- 12054709
TI  - Regeneration of defects in the articular cartilage in rabbit temporomandibular
      joints by bone morphogenetic protein-2.
AB  - The purpose of this study was to investigate the therapeutic use of recombinant
      human bone morphogenetic protein-2 (rhBMP-2) in internally deranged
      temporomandibular joints (TMJ). Defects (2 mm in diameter) were created in the
      surface of the condylar head. Lyophilized rhBMP-2 with collagen as the carrier
      was implanted in the defects in different doses: rhBMP-2 15 microg (n = 5); rhBMP
      2 3 microg (n = 5); rhBMP-2 0.6 microg (n = 5). In the two control groups, the
      defects were either filled with collagen alone (n = 5) or left untreated (n = 5).
      Three weeks postoperatively the sites of defects were examined under light
      microscopy. In the 15 micromg and the 3 microg groups, new cartilage had filled
      the defects; endochondral ossification was also found deep within the defect. In
      the 0.6 microg group, fibrous tissue was proliferating in most areas of the
      defect, although cartilage was also found in some parts. In the two control
      groups, there was either soft tissue repair only or no evidence of tissue repair.
      These findings suggest that BMP-2 could stimulate the repair of defects in the
      articular cartilage of the mandibular condyle head during the 3 weeks
      postoperatively. To observe the progress of endochondral ossification in more
      detail, it may be necessary to extend the experiment for a longer period of time.
      However, this study supports the contention that BMP-2 may be useful in the
      regeneration of cartilage in TMJ disease.

PMID- 12054711
TI  - Primary ectopic thyroid papillary carcinoma in the floor of the mouth and tongue:
      a case report.
AB  - We report a rare case of papillary carcinoma in the tongue and floor of the mouth
      with metastasis in cervical lymph nodes. Treatment was by total thyroidectomy
      with right radical lymph node dissection of the neck, followed by 60 Gy of
      radiotherapy and 100 mCi (131)I. Pathological examination of the thyroid gland
      showed no primary cancer. We review publications about ectopic thyroid and the
      value of antithyroglobulin immunostaining for diagnosis and treatment of the
      tumour.

PMID- 12054712
TI  - Syndrome of inappropriate antidiuretic hormone secretion associated with oral
      squamous cell carcinoma.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is
      associated with various conditions including malignant disease, particularly
      small cell lung cancer. It has been reported to occur in 3% of patients with head
      and neck cancer. Less well known is its association with oral squamous cell
      carcinoma. This report describes a patient with SIADH associated with recurrent
      oral squamous cell carcinoma.

PMID- 12054713
TI  - MRI in the assessment of internal derangement and pain within the
      temporomandibular joint: a pictorial essay.
AB  - In this pictorial essay we aim to illustrate the normal temporomandibular joint
      (TMJ) and the common abnormalities of the osseous, cartilaginous and soft tissue
      components. These include disc (meniscus) displacement, deformities and
      perforations, abnormalities of disc and condylar movement, joint effusions,
      synovial proliferation, condylar deformity and erosions, degenerative change and
      abnormal retrodiscal enhancement.

PMID- 12054714
TI  - Parapharyngeal metastasis from papillary microcarcinoma of thyroid: report of a
      case diagnosed by peroral fine needle aspiration.
AB  - A parapharyngeal metastasis from primary thyroid carcinoma is rare and a search
      of relevant publications disclosed only seven previous reported cases. We
      describe a 46-year-old man who presented with a left parapharyngeal mass that was
      subsequently diagnosed by peroral fine-needle aspiration as a metastasis
      originating from a papillary carcinoma of the thyroid gland. Metastatic thyroid
      cancer should be considered in the differential diagnosis of a parapharyngeal
      mass. Fine-needle aspiration cytology is a simple, speedy, and cost-effective
      method of diagnosis of parapharyngeal masses.

PMID- 12054715
TI  - An experimental model of osteoarthrosis of the temporomandibular joint in
      monkeys.
AB  - The purpose of this study was to develop a model of osteoarthrosis of the
      temporomandibular joint in monkeys, which is remarkably similar in structure and
      function to that of humans. Nine juvenile monkeys, two as controls and seven as
      an experimental group, were used in this study. In the experimental group, the
      articular eminence on both sides was surgically made steeper. Two animals were
      killed at 1 week, four at 6 months, and one at 1 year postoperatively and the
      temporomandibular joints were examined macroscopically and microscopically.
      Typical changes of osteoarthrosis were observed in the 6-month and 1-year
      specimens. These comprised clustering of chondrocytes which resulted in vertical
      and horizontal splitting in the articular cartilage, and fibrillation of the
      articular surface resulting in fibrous union in the joint cavity. These
      degenerative changes advanced progressively over time. Slight anterior
      displacement and degenerative changes in the articular disc were also seen.

PMID- 12054716
TI  - Use of an orthopaedic fixator for external fixation of the mandible.
AB  - A patient presented with a chronically infected, non-united fracture of the
      mandible, with considerable bone loss. He was treated with a metacarpal fixator,
      the miniPennig external fixator. The fixator is stable and smaller than
      conventional mandibular fixators. It can be applied and removed under local
      anaesthesia, if necessary, requires little maintenance and produces minimal
      scarring. The successful outcome in this patient is encouraging and we commend
      the use of the fixator in similar difficult cases.

PMID- 12054717
TI  - Complications with intermaxillary fixation screws in the management of fractured
      mandibles.
AB  - A dedicated bicortical bone screw for temporary intraoperative intermaxillary
      fixation (IMF) during open reduction and fixation of mandibular fractures offers
      many benefits to surgeons and patients. We have used this system for 2 years and
      confirm the benefits over traditional methods of intermaxillary fixation.
      However, complications can arise. One hundred and twenty-two patients with
      mandibular fractures had IMF screws of which five (4%) developed complications
      intraoperatively and postoperatively. Complications included fracture of the
      screws on insertion, iatrogenic damage to teeth causing loss and bony sequestra
      around the area of screw placement.

PMID- 12054718
TI  - Cryosurgical treatment of genuine trigeminal neuralgia.
AB  - A newly developed cryoprobe for peripheral nerves allows surgeons to freeze
      branches of the trigeminal nerve at the infraorbital or the mandibular foramen
      without exposing the nerve or damaging the surrounding tissue. The probe has an
      outer diameter of 2.7mm, and a vacuum-insulated shaft to protect the adjacent
      tissue. It is designed to be inserted transmucosally. The cryoprobe was used in
      19 patients to freeze the infraorbital nerve or the inferior alveolar nerve. At 4
      8 months after cryotherapy sensation in the areas innervated by the treated nerve
      had returned, but pain was absent for at least 6 months. The pain recurred in 13
      out of 19 patients within 6-12 months. However, it was possible to repeat the
      cryotherapy as the procedure was not stressful. Cryosurgery widens the range of
      methods available to treat trigeminal neuralgia.

PMID- 12054719
TI  - Can warfarin be continued during dental extraction? Results of a randomized
      controlled trial.
AB  - A randomized controlled trial was set up to investigate whether patients who were
      taking warfarin and had an International Normalised Ratio (INR) within the normal
      therapeutic range require cessation of their anticoagulation drugs before dental
      extractions. Of 109 patients who completed the trial, 52 were allocated to the
      control group (warfarin stopped 2 days before extraction) and 57 patients were
      allocated to the intervention group (warfarin continued). The incidence of
      bleeding complications in the intervention group was higher (15/57, 26%) than in
      the control group (7/52, 14%) but this difference was not significant. Two
      patients in the study required hospital review for bleeding and all other
      episodes of bleeding were controlled by patients at home. Continuing warfarin
      when the INR is < 4.1 may lead to an increase in minor post-extraction bleeding
      after dental extractions but we found no evidence of an increase in clinically
      important bleeding. As there are risks associated with stopping warfarin, the
      practice of routinely discontinuing it before dental extractions should be
      reconsidered.

PMID- 12054720
TI  - Intracranial dislocation of the mandibular condyle: report of two cases and
      review of the literature.
AB  - Fractures of the mandibular condylar process are common and account for up to 40%
      of all mandibular fractures. Penetration of the condylar head into the middle
      cranial fossa is, however, rare. We have found reports of only 43 cases since
      1834. The diagnosis of intracranial condylar dislocation is difficult, there are
      usually no particular symptoms or neurological signs. As a result, detailed
      radiological studies are necessary. In the absence of clear radiographic images
      of the condylar structures, computed tomography (CT) is essential to locate the
      fragments and to investigate and monitor intracranial lesions. This paper
      describes the diagnostic and surgical procedures used in two cases of condylar
      dislocation and discusses them with reference to previous cases. The use of a
      titanium screw, which was positioned intracranially in the first case, has not,
      to our knowledge, been described previously.

PMID- 12054721
TI  - Occult lymph node metastases posterior to the internal jugular vein.
AB  - Supraomohyoid neck dissection is a reliable staging procedure in patients with
      oral or oropharyngeal squamous cell carcinoma and no clinical evidence of node
      metastases. We have recorded the yield and distribution of occult lymph node
      metastases in the fibro-fatty strip of tissue posterior to the internal jugular
      vein and beneath the sternomastoid in 35 neck dissections. Occult lymph node
      metastases were found in 12/35 (34%); 3 of these had metastases in the posterior
      strip, which were never in isolation. We think that it is worthwhile to sample
      the posterior strip. Firstly it removes tumour that would have been left behind
      in a small number of cases had a conventional supraomohyoid neck dissection been
      done, and secondly it enables postoperative radiotherapy to be targeted at the
      anterior triangle alone when the posterior strip is clear of tumour.

PMID- 12054722
TI  - Assessment of free fibula flaps: a cautionary note.

PMID- 12054723
TI  - A method of skeletal anchorage for maxillary distraction.
AB  - A simple method of providing skeletal anchorage in maxillary distraction is
      described. The method utilizes cheap and readily available miniplates and
      provides rigid fixation to the fragment. It can be utilized at multiple levels in
      high-level osteotomies and situations with an inadequate dentition for anchorage.

PMID- 12054724
TI  - Role for sulcus deepening sutures in reconstructive surgery.

PMID- 12054725
TI  - Trapezius muscle innervation by a cervical nerve--a rare anatomical variant.

PMID- 12054726
TI  - Metronidazole: avoid it unless it's very much indicated (avoid its routine
      prescription).

PMID- 12054727
TI  - Surgical training programme.

PMID- 12054728
TI  - The pen is not mightier than the sword.

PMID- 12054729
TI  - Re: Webster K, Wilde J. Management of anticoagulation in patients with prosthetic
      heart valves undergoing oral and maxillofacial operations. Br J Oral Maxillofac
      Surg 2000; 38: 124-126.

PMID- 12054731
TI  - Dipeptidyl peptidase IV inhibition as an approach to the treatment and prevention
      of type 2 diabetes: a historical perspective.

PMID- 12054732
TI  - Synthesis, aggregation, neurotoxicity, and secondary structure of various A beta
      1-42 mutants of familial Alzheimer's disease at positions 21-23.
AB  - Cerebral amyloid angiopathy (CAA) due to amyloid beta (A beta) deposition is a
      key pathological feature of Alzheimer's disease (AD), especially in some form of
      familial Alzheimer's disease (FAD) including hereditary cerebral hemorrhage with
      amyloidosis-Dutch type. A beta mainly consists of 40- and 42-mer peptides (Abeta
      1-40 and A beta 1-42), which accumulate in senile plaques of AD brains and show
      neurotoxicity for cultured nerve cells. We synthesized all variant forms of A
      beta 1-42 associated with reported FAD, such as A21G (Flemish), E22Q (Dutch),
      E22K (Italian), E22G (Arctic), and D23N (Iowa) along with three potential mutants
      by one point missense mutation (E22A, E22D, and E22V) in a highly pure form, and
      examined their ability to aggregate and their neurotoxicity in PC12 cells. The
      mutants at positions 22 and 23 showed potent aggregative ability and
      neurotoxicity whereas the potential mutants did not, indicating that A beta 1-42
      mutants at positions 22 and 23 play a critical role in FAD of Dutch-, Italian-,
      Arctic-, and Iowa-types. However, Flemish-type FAD needs alternative explanation
      except the aggregation and neurotoxicity of the corresponding A beta 1-42 mutant.

PMID- 12054733
TI  - Luteinizing hormone-releasing hormone induces JunD-DNA binding and extends cell
      cycle in human ovarian cancer cells.
AB  - Expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as
      part of an autocrine regulatory system of cell proliferation has been
      demonstrated in a number of human malignant tumors, including cancers of the
      ovary. This study was conducted to investigate whether LHRH induces activation of
      JunD and affects cell cycle regulation and DNA synthesis. Treatment of primary
      human ovarian cancer cells and human ovarian cancer cell lines EFO-21 and EFO-27
      with LHRH agonist triptorelin (100 nM) resulted in an increase in G(0/1) phase
      and a decrease in G(2/S) phase of cell cycle. Treatment of quiescent EFO-21 or
      EFO-27 cells with triptorelin (100 nM) resulted in a 46.7 or 44.2-fold increase
      of AP-1 activation, respectively (p<0.001). Maximal binding of JunD on DNA
      consensus sequence was found after 4 h of treatment of quiescent EFO-21 or EFO-27
      cells with triptorelin (100 nM). DNA synthesis was significantly decreased to
      45.5+/-11.4% (day 0=control=100%; p<0.001) after 3 days of triptorelin (1 nM)
      treatment. These results suggest that LHRH agonist triptorelin induces JunD-DNA
      binding, resulting in reduced proliferation as indicated by increased G(0/1)
      phase of cell cycle and decreased DNA synthesis. Since LHRH activates nucleus
      factor kappa B (NF kappa B) and protects ovarian cancer cells from doxorubicin
      induced apoptosis and JunD is shown to decrease cell cycle and cell
      proliferation, we propose that JunD activated by LHRH acts as a modulator of cell
      proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions
      of LHRH.

PMID- 12054734
TI  - NS3 protease of Langat tick-borne flavivirus cleaves serine protease substrates.
AB  - Langat (LGT) virus, initially isolated in 1956 from ticks in Malaysia, is a
      naturally occurring nonpathogenic virus with a very close antigenicity to the
      highly pathogenic tick-borne encephalitis (TBE) Western subtype virus and TBE Far
      Eastern subtype virus. NS3, the second largest viral protein of LGT virus, is
      highly conserved among flaviviruses and contains a characteristic protease moiety
      (NS3 pro). NS3 pro represents an attractive target for anti-protease molecules
      against TBE virus. We report herein a purification method specially designed for
      NS3 pro of LGT using a strategy for proper refolding coupled with the enzymatic
      characterisation of the protein. Different p-nitroanilide substrates, defined on
      canonic sequences for their susceptibility to Ser-protease, were applied to the
      proteolytic assays of the protein. The highest values were obtained from
      substrates containing an Arg or Lys (amino acid) residue at the P1 position. This
      purification method will facilitate the future development of reliable testing
      procedures for anti-proteases directed to NS3 proteins.

PMID- 12054735
TI  - A complex containing PBX2 contributes to activation of the proto-oncogene HOX11.
AB  - Ectopic expression of the homeobox gene HOX11 is associated with a significant
      proportion of childhood T-cell acute lymphoblastic leukaemias (T-ALLs). We
      hypothesise that one mechanism of gene deregulation involves overcoming the
      silencing mechanism(s) of gene expression present in normal cells. Here, we
      describe a search for trans-acting factors that control transcriptional activity
      from a distal 5' region of the HOX11 promoter. We have identified a region of
      this promoter which contributes significantly to HOX11 activation and two
      distinct regulatory elements are involved. First, a PBX2 Regulatory Element PRE
      1048 has been identified which contains a novel DNA-binding sequence and mediates
      significant activation of the HOX11 gene in K562 cells. This is the first report
      of a homeobox gene being specifically regulated by PBX2 and the second report of
      a vertebrate homeobox target gene of a PBX protein. The PREP1 protein was also
      shown to be part of the PRE-1048-binding complex. The other regulatory element we
      describe here RE-1019 contains little sequence conservation to known
      transcription control elements. It appears that this element is a novel sequence
      that binds an as yet unidentified factor, mediating significant activation of the
      HOX11 gene in K562 cells. This is the first detailed report of elements that
      mediate regulation of the proto-oncogene HOX11.

PMID- 12054736
TI  - Dimerization of v-erbA on inverted repeats.
AB  - Thyroid hormone receptors (TRs) and the oncoprotein v-erbA can heterodimerize
      with retinoid X receptor (RXR) on core motifs arranged as inverted repeats (IR0)
      which contain the consensus sequence AGGTCA. On this core motif, v-erbA can also
      form homodimers whereas TRs homodimerize very poorly. Therefore to obtain a
      better understanding of distinct homodimerization properties of TR alpha 1 as
      compared to those of v-erbA, we created chimeras between these two receptors and
      tested their abilities to homodimerize on IR0. We found that the enhanced
      homodimerization properties of v-erbA compared to those of TR alpha 1 on IR0 map
      to amino acids 107-156 in v-erbA/121-170 in TR alpha 1 (VT-2 chimera).
      Furthermore, functional studies on transient transfections showed that v-erbA-RXR
      heterodimers do not mediate the dominant negative activity of v-erbA on an
      inverted repeat response element. These data, in conjunction with our previous
      studies, indicate that v-erbA homodimers mediate the repressor activity of v-erbA
      on IR0.

PMID- 12054737
TI  - The inhibitory and facilitatory actions of amyloid-beta peptides on nicotinic ACh
      receptors and AMPA receptors.
AB  - The present study investigated the effects of amyloid-beta peptides on nicotinic
      ACh receptors (Torpedo, alpha 4 beta 2, and alpha 7 receptors) and AMPA receptors
      expressed in Xenopus oocytes by monitoring whole-cell membrane currents. Ten
      minutes treatment with amyloid-beta(1-42) (1 microM) inhibited Torpedo ACh
      receptor currents, reaching 53% of original levels 30 min after treatment.
      Amyloid-beta(1-40) inhibited the currents in a dose-dependent manner (0.1-10
      microM) during treatment, gradually reversing after treatment. Amyloid-beta(1-40)
      and amyloid-beta(1-42) (0.1 microM) depressed alpha 4 beta 2 receptor currents to
      each 69% and 62% of original levels at 10-min treatment and lesser depression was
      obtained with alpha 7 receptors. Amyloid-beta(1-42) (0.1 microM) did not
      significantly inhibit AMPA receptor currents, but amyloid-beta(1-40) (0.1 microM)
      potentiated the currents to 145-191% of original levels. Amyloid-beta peptides,
      thus, exert their diverse actions on nicotinic ACh receptors and AMPA receptors,
      and the inhibitory actions on nicotinic ACh receptors may account for the
      deterioration of learning and memory in Alzheimer's disease.

PMID- 12054738
TI  - Liver- and lobe-selective gene transfection following the instillation of plasmid
      DNA to the liver surface in mice.
AB  - The present study has undertaken the liver- and lobe-selective gene transfections
      following the instillation of plasmid DNA (pDNA) to the liver surface in mice.
      The luciferase levels produced in the applied (left) liver lobe at 6 h after
      liver surface instillation of pDNA were significantly higher than those produced
      in the other tissues assayed, and ranged from 8.5-fold higher in other liver
      lobes to 320-fold higher in other tissues. After small intestine surface
      instillation of pDNA, the gene expression was a little detected in the tissues
      assayed. Following liver surface instillation of pDNA at a time from 2 to 48 h or
      at a volume from 15 to 120 microl, the gene expressions of the applied liver lobe
      were always significantly higher than those of other liver lobes and other
      tissues. We demonstrated the novel liver- and lobe-selective gene transfection
      utilizing the instillation to the liver surface.

PMID- 12054740
TI  - Crystallization and preliminary crystallographic analysis of manganese superoxide
      dismutase from Bacillus halodenitrificans.
AB  - Manganese superoxide dismutase (GP-MnSOD), a component of the so-called 'green
      protein' (green protein complex) from the facultative anaerobic halodenitrifier
      Bacillus halodenitrificans, has been crystallized using the hanging-drop vapor
      diffusion method. Crystals have unit-cell parameters a=b=93.4 A, c=65.0 A, and
      belong to the space group P4(3)2(1)2. Preliminary analysis indicates there is one
      monomer in each asymmetric unit. The structural information from this enzyme will
      enrich our knowledge on its high catalytic activity and its possible role in
      green protein complex.

PMID- 12054739
TI  - Induction of apoptosis in granulosa cells by TNF alpha and its attenuation by
      glucocorticoids involve modulation of Bcl-2.
AB  - Tumor necrosis factor alpha (TNF alpha) plays a role in mammalian ovarian
      follicular development, steroidogenesis, ovulation, luteolysis, and atresia, but
      the exact mechanism of TNF alpha action is not completely understood. Induction
      of apoptosis and suppression of steroidogenesis by TNF alpha in primary
      preovulatory rat and human granulosa cells, as well as, in human granulosa cells
      immortalized by mutated p53, were characterized in the present work.
      Dexamethasone (Dex) and hydrocortisone efficiently suppressed TNF alpha-induced
      apoptosis in granulosa cells. TNF alpha dramatically reduced intracellular levels
      of Bcl-2, while Dex abrogated this reduction. TNF alpha reduced considerably
      intracellular levels of StAR protein, a key regulating factor in steroidogenesis.
      This reduction can be explained only in part by elimination of cells through
      apoptosis, since loss of steroidogenic capacity was much higher and faster than
      the rate and extent of loss of cell viability induced by TNF alpha, suggesting
      independent mechanisms for TNF alpha-induction of apoptosis and TNF alpha
      suppression of steroidogenesis.

PMID- 12054741
TI  - Induction of murine H-rev107 gene expression by growth arrest and histone
      acetylation: involvement of an Sp1/Sp3-binding GC-box.
AB  - H-rev107 is downregulated in many carcinomas and tumor cell lines. Using
      postconfluent NIH3T3 cells, we demonstrated that growth arrest caused by contact
      inhibition, but not serum deprivation, increased H-rev107 expression.
      Furthermore, histone deacetylase inhibitors induced H-rev107 expression in NIH3T3
      cells and allowed its reexpression in H-rev107-deficient WEHI 7.1 lymphoma cells.
      In contrast, no effect of the postconfluent stage or histone deacetylase
      inhibitors on H-rev107 levels was observed in tumorigenic H-rev107-expressing
      cell lines, HepG2, HeLa, and SKBR3. Transfections showed that TSA treatment
      increased luciferase activity 20-fold in NIH3T3 cells. We found that the GC-box
      at -83/-75 is a key element for H-rev107 induction by TSA and growth arrest,
      although there were no changes in the pattern and intensity of Sp1/Sp3-binding
      after induction. These data suggest that contact inhibition of growth and growth
      arrest caused by histone deacetylase inhibitors probably use the same mechanism
      to stimulate H-rev107 expression via histone acetylation in NIH3T3 cells and this
      might contribute to the development of drugs that can induce H-rev107 expression
      in certain tumors.

PMID- 12054742
TI  - Isoprene synthase activity parallels fluctuations of isoprene release during
      growth of Bacillus subtilis.
AB  - Isoprene is a volatile metabolite of uncertain function in plants, animals, and
      bacteria. Here, we demonstrate that the isoprene-producing bacterium, Bacillus
      subtilis, contains an isoprene synthase activity that catalyzes dimethylallyl
      diphosphate-dependent isoprene formation. Although the enzyme was very labile, it
      was demonstrated in both permeabilized cells and in partially purified cell
      extracts. Its activity was optimal at pH 6.2, required low levels of a divalent
      cation, and appears distinct from chloroplast isoprene synthases. When grown in a
      bioreactor, B. subtilis cells released isoprene in three distinct phases; using
      permeabilized cells, it was shown that isoprene synthase activity rose and fell
      in parallel with each phase. These results suggest that isoprene synthesis is
      highly regulated in B. subtilis and further research in this model system may
      shed light on the role of isoprene formation in biological systems.

PMID- 12054743
TI  - A bacterial flavin reductase system reduces chromate to a soluble chromium(III)
      NAD(+) complex.
AB  - Biological reduction of carcinogenic chromate has been extensively studied in
      eukaryotic cells partly because the reduction produces stable chromium(III)-DNA
      adducts, which are mutagenic. Microbial reduction of chromate has been studied
      for bioremediation purposes, but little is known about the reduction mechanism.
      In eukaryotic cells chromate is mainly reduced non-enzymatically by ascorbate,
      which is usually absent in bacterial cells. We have characterized the reduction
      of chromate by a flavin reductase (Fre) from Escherichia coli with flavins. The
      Fre-flavin system rapidly reduced chromate, whereas chemical reduction by NADH
      and glutathione was very slow. Thus, enzymatic chromate reduction is likely the
      dominant mechanism in bacterial cells. Furthermore, the end-product was a soluble
      and stable Cr(III)-NAD(+) complex, instead of Cr(III) precipitate. Since
      intracellularly generated Cr(III) forms adducts with DNA, protein, glutathione,
      and ascorbate in eukaryotic cells, we suggest that the produced Cr(III) is
      primarily complexed to NAD(+), DNA, and other cellular components inside
      bacteria.

PMID- 12054744
TI  - Module fusion in an A-type flavoprotein from the cyanobacterium Synechocystis
      condenses a multiple-component pathway in a single polypeptide chain.
AB  - The A-type flavoproteins (ATF) are modular proteins involved in multi-component
      electron transfer pathways, having oxygen reductase activity. They are complex
      flavoproteins containing two distinct structural domains, one having an FMN in a
      flavodoxin-like fold and the other a binuclear iron centre within a metallo-beta
      lactamase-like fold. Here, we report the purification and characterisation of a
      recombinant ATF from the cyanobacterium Synechoystis sp. PCC 6803, which has the
      unique feature of comprising an additional third domain with similarities towards
      flavin:NAD(P)H reductases. The latter was expressed independently as a truncated
      protein form and found to be capable of receiving electrons from NADH as well as
      to indiscriminately bind either one FAD or one FMN with equivalent affinities.
      Further kinetic studies have shown that the intact ATF is an NADH:oxygen
      oxidoreductase, with the catalytic ability to fully reduce oxygen to water. Thus,
      this constitutes an example on how structural modules found within partner
      proteins from an electron transfer pathway can be combined in a single
      polypeptide chain achieving identical catalytic activities.

PMID- 12054746
TI  - Gender differences in steroid modulation of angiotensin II-induced protein kinase
      C activity in anterior pituitary of the rat.
AB  - To investigate whether the various steroid hormones can modulate the basal and
      angiotensin II-induced protein kinase C (PKC) activity in the anterior pituitary
      of the rat, female and male intact and ovariectomized female Wistar rats were
      treated in vivo with estradiol (E2), progesterone (P), dehydroepiandrostendione
      sulfate (DHEA-S), and pregnenolone sulfate (PREG-S). Estradiol caused the
      increase of basal PKC activity in intact and ovariectomized females, but did not
      change the enzyme activity in males. In ovariectomized animals the increase of
      PKC activity was lower than in intact females. Progesterone decreased PKC
      activity only in intact animals. DHEA-S strongly enhanced activity of PKC in
      ovariectomized females. Pregnenolone sulfate did not significantly change PKC
      function of all studied groups. Incubation with AngII enhanced the PKC activity
      in intact (without steroid treatment) animals of both genders. In females, AngII
      and estradiol together rise the PKC-stimulated phosphorylation in greater degree
      than used separately. Treatment with other investigated steroids reduced the
      effect of AngII. In intact males every examined hormone turned back the
      stimulatory effect of AngII on PKC activity. These data suggest that gender
      differences in PKC activity are likely related to hormonal milieu of experimental
      animals and may depend in part on the basic plasma level of estrogens.

PMID- 12054745
TI  - Deficiency in sPLA(2) does not affect HDL levels or atherosclerosis in mice.
AB  - Secretory non-pancreatic phospholipase A(2) (sPLA(2)) has been implicated in
      inflammation and has been found in human atherosclerotic lesions. To test the
      effect of sPLA(2) deficiency on atherosclerosis, C57BL/Ks mice (apoE(+/+) and
      PLA(2)(++) were bred with C57BL/6 apoE knockout mice which are sPLA(2)(--) due to
      a spontaneous mutation. Sibling pairs of mice (apoE(--)/sPLA(2)(++) and apoE(-
      )/sPLA(2)(--)) on high fat Western diets were dissected at 22 weeks. In vitro
      enzyme assays confirmed higher serum sPLA(2) activity in the sPLA(2)(++) compared
      to sPLA(2)(--) for both sexes, while sPLA(2)(--) males had slightly higher serum
      cholesterol and phospholipids. Analysis of lipoprotein profiles by FPLC showed no
      effect of sPLA(2) genotype on any measured parameters. Atherosclerosis was
      quantitated by assaying cholesterol in aortic extracts. Male sPLA(2) trended
      slightly higher than sPLA(2)(++) with no statistical significance. Female
      sPLA(2)(++) and sPLA(2)(--) mice showed no significant differences in any of the
      measured parameters. These results suggest that the endogenous mouse sPLA(2) gene
      does not significantly affect HDL or atherosclerosis in mice.

PMID- 12054748
TI  - NBT-II carcinoma behaviour is not dependent on cell-cell communication through
      gap junctions.
AB  - To study the mechanism(s) underlying the proliferation of heterogeneous cell
      populations within a solid tumour, the NBT-II rat bladder carcinoma system was
      used. It has been first investigated whether the different cell populations are
      coupled through gap junctions (GJIC). Cells overexpressing the Cx43 were
      generated to test for any tumour suppressive activity in vivo. To determine
      whether GJIC is essential for tumour proliferation and the establishment of a
      cooperative community effect, NBT-II cells that are incompetent for cell coupling
      were generated. The data report that (i) carcinoma cells expressing or not FGF-1
      are coupled through GJIC in vitro and in coculture and express the gap junction
      protein Cx43, (ii) overexpression of Cx43 in these cells does not affect their in
      vitro coupling capacities and in vivo tumourigenic growth properties, (iii)
      inhibition of GJIC through antisense strategy has no in vivo obvious consequence
      on the tumour growth properties of the carcinoma, and (iv) the community effect
      between two carcinoma cell populations does not critically involve cell coupling
      through gap junctions.

PMID- 12054747
TI  - Benzo(a)pyrene, but not 2,3,7,8-tetrachlorodibenzo-p-dioxin, alters cell adhesion
      proteins in human uterine RL95-2 cells.
AB  - This study compared the effects of benzo(a)pyrene (BaP) and 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), two aryl hydrocarbon receptor agonists, on
      cell attachment and adherens junction proteins in RL95-2 human uterine
      endometrial cells. Exposure to 10 microM BaP significantly decreased cell
      attachment to Matrigel, whereas 10 nM TCDD had no effect. Immunocytochemistry and
      Western immunoblot analysis showed that BaP, but not TCDD, produced a marked loss
      of plasma membrane epidermal growth factor receptor (EGF-R) localized along
      intercellular boundaries. BaP-treated cells exhibited significant decreases in
      beta-catenin and cadherin protein levels, while vinculin levels remained
      unchanged relative to control. In contrast, TCDD treatment had no effect on the
      levels of beta-catenin, cadherin, or vinculin. Further studies using the
      fluorescein labeled peptide phalloidin showed the presence of continuous
      subcortical actin filaments in control cells, whereas BaP-treated cells had
      subcortical actin aggregates. Thus, in contrast to TCDD, BaP produces a loss of
      cell attachment involving decreased localization of molecules important for cell
      cell interactions in RL95-2 cells.

PMID- 12054749
TI  - Cellular localisation of a water-soluble fullerene derivative.
AB  - Fullerenes are a new class of compounds with potential uses in biology and
      medicine and many insights were made in the knowledge of their interaction with
      various biological systems. However, their interaction with organised living
      systems as well as the site of their potential action remains unclear. In this
      work, we have demonstrated that a fullerene derivative could cross the external
      cellular membrane and it localises preferentially to the mitochondria. We propose
      that our finding supports the potential use of fullerenes as drug delivery agents
      as their structure mimics that of clathrin known to mediate endocytosis.

PMID- 12054751
TI  - Differential localisation of nPKC delta during cell cycle progression.
AB  - nPKC delta is a phospholipid-dependent and calcium-independent PKC isoform, whose
      over expression in BL6T murine melanoma cells, modifies their proliferative and
      metastatic potential in vivo. We focus here on the possible relationship between
      the subcellular localisation of nPKC delta and distinct phase of the cell cycle.
      Our findings show a dynamic localisation of nPKC delta in dependence of the phase
      of the cell cycle. Actually, this isoform is preferentially localised to the
      cytoplasm in serum-starved cells, shifting to the nucleus during the S-phase and
      becoming peri-nuclear, associated to the Golgi apparatus, in G2-M phase.
      Therefore, taken together our findings demonstrate that the subcellular
      localisation of nPKC delta changes dynamically during the cell cycle in
      dependence of the requirement of the enzyme at a particular place of the cell.

PMID- 12054750
TI  - The APC regulator CDH1 is essential for the progression of embryonic cell cycles
      in Xenopus.
AB  - The orderly progression of cell cycle depends on timely destruction of key
      regulators through ubiquitin-mediated proteolysis. The anaphase-promoting complex
      (APC) is a major component of this degradation machinery and its activation is
      regulated by CDC20 and CDH1. We demonstrate here that CDH1 mRNA is ubiquitously
      expressed in Xenopus embryos of all developmental stages. Loss of CDH1 function
      during early embryonic cell cycles leads to an immediate and prolonged arrest
      with low cyclin-dependent kinase activity. In contrast, ectopic overexpression of
      CDH1 induces cell cycle arrest during the first G(1) phase at the midblastula
      transition. CDH1-dependent degradation of cyclin A is likely involved in this
      G(1) arrest. Our findings establish the essential roles of CDH1 in embryonic cell
      cycles.

PMID- 12054752
TI  - Propionic acid side chain hydrogen bonding in the malaria pigment beta-hematin.
AB  - Malaria pigment, or beta-hematin, the insoluble heme detoxification product
      resulting from the intraerythrocitic digestion of hemoglobin by young malaria
      trophozoites has been structurally characterized by X-ray powder diffraction and
      shown to contain chains of propionic acid linked dimers. Although there is
      considerable spectroscopic evidence for a monodentate propionate-iron interaction
      in this crystalline material, the spectroscopic characterization of the propionic
      acid dimer is limited. Herein we demonstrate the presence of the propionic acid
      dimer unit by H/D isotope substitution in carboxylic acid dimer. In the Raman
      spectrum of the deuterium substituted compound there is a circa 12 cm(-1) shift,
      H: 1629 cm(-1) vs. D: 1617 cm(-1) in the symmetric ring breathing mode for the
      propionic acid dimer. On the other hand, the IR active asymmetric stretch has a
      very small shift, <3 cm(-1), upon deuteration. These, and other vibrational data,
      are consistent with the presence of a planar carboxylic acid dimer in the
      structure of beta-hematin.

PMID- 12054753
TI  - Cloning and characterization of a testis and brain-specific isoform of mouse 3'
      phosphoinositide-dependent protein kinase-1, mPDK-1 beta.
AB  - 3'-Phosphoinositide-dependent protein kinase-1 (PDK-1) phosphorylates and
      activates members of the protein kinase AGC family and plays a key role in
      receptor tyrosine kinase signaling. Here we report the cloning and
      characterization of a splice variant of mouse PDK-1, mPDK-1 beta. The cDNA
      encoding mPDK-1 beta contains two alternative start codons and translation from
      these start codons generates proteins that are, respectively, 27 or 51 amino acid
      residues shorter at the amino-terminus than the previously identified PDK-1
      isolated from mouse liver (now renamed mPDK-1 alpha) [J. Biol. Chem. 274 (1999)
      8117]. Analysis of mouse tissues shows that mPDK-1 beta is highly expressed in
      the testis and various functional regions of the brain. Expression of this
      isoform is increased in the brain of aged mice. Both mPDK-1 alpha and mPDK-1 beta
      are autophosphorylated at both serine and threonine residues in vitro and showed
      similar levels of tyrosine phosphorylation when co-expressed with either
      constitutively active Src or Fyn tyrosine kinases in cells. However, the mPDK-1
      isoforms showed significant differences in their response to pervanadate- or
      insulin plus vanadate-stimulated tyrosine phosphorylation. Taken together, our
      findings suggest that the two PDK-1 isoforms may be differentially regulated in
      cells. The specific expression of mPDK-1 beta in mouse testis and brains of aged
      mice also suggests potential involvement of this kinase in regulating animal
      spermatogenesis and aging.

PMID- 12054754
TI  - Native transfer RNA catalyzes Diels-Alder reaction.
AB  - In this paper we show that transfer ribonucleic acids (tRNAs) catalyze the Diels
      Alder cycloaddition reaction. A new DNA oxidative damage product, 6
      furfuryladenine (kinetin) or its riboside (diene), was transformed with dimethyl
      acetylenedicarboxylate or maleic anhydride (dienophile). The reaction proceeds in
      the presence of tRNA at high pressure but not at ambient condition. If so tRNA in
      prebiotic conditions (RNA world) had at least two functions: catalytic and a
      carrier of genetic information. It means that tRNA at high pressure shows
      catalytic properties and is a true Diels-Alderase.

PMID- 12054755
TI  - Growth factors for sequential cellular de- and re-differentiation in tissue
      engineering.
AB  - A model system for the in vitro generation of cartilaginous constructs was used
      to study a tissue engineering paradigm whereby sequentially applied growth
      factors promoted chondrocytes to first de-differentiate into a proliferative
      state and then re-differentiate and undergo chondrogenesis. Early cultivation in
      medium with supplemental TGF-beta1/FGF-2 doubled cell fractions in 2-week
      constructs compared to unsupplemented controls. Subsequent culture with
      supplemental IGF-I yielded large 4-week constructs with high fractions of
      cartilaginous extracellular matrix (ECM) and high compressive moduli, whereas
      prolonged culture with supplemental FGF-2 yielded small 4-week constructs with
      low ECM fractions and moduli. Sequential supplementation with TGF-beta1/FGF-2 and
      then IGF-I yielded 4-week constructs with type-specific mRNA expression and
      protein levels that were high for type II and negligible for type I collagen, in
      contrast to other growth factor regimens studied. The data demonstrate that
      structural, functional, and molecular properties of engineered cartilage can be
      modulated by sequential application of growth factors.

PMID- 12054756
TI  - The origin of the absorption band induced through the interaction between
      apotransketolase and thiamin diphosphate.
AB  - It has long been known that formation of a catalytically active holotransketolase
      from the apoenzyme and coenzyme (thiamin diphosphate) is accompanied by the
      appearance of a new band, in both the absorption and CD spectra. Binding and
      subsequent conversion of the substrates bring about changes in this band's
      intensity. The observation of these changes allows the investigator to monitor
      the coenzyme-to-apoenzyme binding and the conversion of substrates during the
      transketolase reaction and thus to kinetically characterize its individual steps.
      The origin of the thiamin diphosphate induced absorption band has been postulated
      to be resulted from formation of a charge transfer complex or alternatively from
      an induced conformational transition of the enzyme. The latter brings aromatic
      amino acid residues into close proximity and generates the absorption. However, X
      ray crystallographic and enzyme point mutation experiments cast doubts on both of
      these hypotheses. Here we show that the binding of thiamin diphosphate to the
      apotransketolase leads to the conversion of the 4'-amino tautomeric form of its
      aminopyrimidine ring into the N(1')H-imino tautomeric form. This imino form
      emerges as a result of the coenzyme's aminopyrymidine ring incorporation into the
      hydrophobic pocket of the transketolase active center and is stabilized through
      the interactions with Glu418 and Phe445 residues. The N(1')H-imino tautomeric
      form of thiamin diphosphate is thought to be the origin of the holotransketolase
      absorption band induced through the coenzyme binding.

PMID- 12054757
TI  - A novel gene IC53 stimulates ECV304 cell proliferation and is upregulated in
      failing heart.
AB  - C53, cloned from rat brain cDNA library, can bind to p35, the precursor of
      activator of Cdk5. A novel gene with 84% homolog to C53, named IC53, was cloned
      from our 5300 EST database of human aorta cDNA library (GenBank Accession No.
      AF110322). Computational analysis showed that IC53 cDNA is 2538 bp long, encoding
      419 amino acids, mapped to chromosome 17q21.31 with 12 exons, ubiquitously
      expressed in 12 tested normal tissues and 8 tumor cell lines from MTN membranes
      and vascular endothelial cells by Northern blot and in situ hybridization, and
      upregulated in the rat models of subacute heart failure and chronic ischemic
      heart failure by left coronary ligation. Stable transfection of IC53 stimulates
      ECV304 cell proliferation by 2.1-fold compared to cells with empty vector
      (P<0.05). The results support that IC53 is a novel gene, mainly expressed in
      vascular endothelial cells and mediates cell proliferation.

PMID- 12054758
TI  - Molecular modeling of flavonoids that inhibits xanthine oxidase.
AB  - The inhibition of xanthine oxidase activity by various flavonoids was assessed.
      All of the tested flavonoids were competitive inhibitors, and from the kinetic
      analysis suggested that flavonoids bind to the reactive site. To further
      understand the stereochemistry between these flavonoids and xanthine oxidase,
      structure-based molecular modeling was performed. Apigenin was the most potent
      inhibitor which showed the most favorable interaction in the reactive site. The
      bicyclic benzopyranone ring of apigenin stacked with phenyl of Phe 914, and the
      phenolic group stretched to the space surrounding with several hydrophobic
      residues. Quercetin and myricetin composed a 3-hydroxyl group on benzopyranone
      which resulting in reduction of binding affinity. The phenolic group of genistein
      positioned in opposite orientation comparison with apigenin, and resulted in a
      weaker interaction with xanthine oxidase. Isovitexin showed the weakest
      inhibitory effect among the compounds tested. The bulky group of sugar in
      isovitexin may hamper its interaction with xanthine oxidase.

PMID- 12054759
TI  - Comparative modelling and immunochemical reactivity of Escherichia coli UMP
      kinase.
AB  - Bacterial UMP kinases do not exhibit any sequence homology with other nucleoside
      monophosphate kinases described so far, and appear under oligomeric forms,
      submitted to complex regulation by nucleotides. We propose here a structural
      model of UMP kinase from Escherichia coli based on the conservation of the fold
      of carbamate kinase whose crystal structure was recently solved. Despite sequence
      identity of only 18% over 203 amino acids, alignment of UMP kinase from E. coli
      with carbamate kinase from Enterococcus faecalis by hydrophobic cluster analysis
      and threading suggested the conservation of the overall structure, except for a
      small subdomain (absent in UMP kinase). The modelled dimer suggested conservation
      of the dimer interface observed in carbamate kinase while interaction of UMP
      kinase with a monoclonal antibody (Mab 44-2) suggests a three in-plane dimer
      subunit arrangement. The model was analyzed in light of various modified forms of
      UMP kinase obtained by site-directed mutagenesis.

PMID- 12054760
TI  - The design, synthesis, and biochemical evaluation of derivatives of biphenyl
      sulfamate-based compounds as novel inhibitors of estrone sulfatase.
AB  - We report the initial results of our study into the use of a potential transition
      state (TS) of the reaction catalyzed by the enzyme estrone sulfatase (ES) in the
      design of a series of simple 4'-O-sulfamoyl-4-biphenyl-based compounds as novel
      inhibitors of ES. The results of the study show that these compounds are: potent
      inhibitors, possessing greater inhibitory activity than 4-methylcoumarin-7-O
      sulfamate (COUMATE); weaker inhibitors than the tricyclic derivative of COUMATE,
      namely 667-COUMATE and the steroidal inhibitor estrone-3-O-sulfamate (EMATE), and
      irreversible inhibitors of ES.

PMID- 12054761
TI  - Domain-swapped structure of a mutant of cyanovirin-N.
AB  - Cyanovirin-N (CV-N) is a potent 11 kDa HIV-inactivating protein that binds with
      high affinity to the HIV surface envelope protein gp120. A double mutant
      P51S/S52P of CV-N was engineered by swapping two critical hinge-region residues
      Pro51 and Ser52. This mutant has biochemical and biophysical characteristics
      equivalent to the wild-type CV-N and its structure resembles that of wild-type CV
      N. However, the mutant shows a different orientation in the hinge region that
      connects two domains of the protein. The observation that this double mutant
      crystallizes under a wide variety of conditions challenges some of the current
      hypotheses on domain swapping and on the role of hinge-region proline residues in
      domain orientation. The current structure contributes to the understanding of
      domain swapping in cyanovirins, permitting rational design of domain-swapped CV-N
      mutants.

PMID- 12054762
TI  - Expression, purification, and evidence for the interaction of the two nucleotide
      binding folds of the sulphonylurea receptor.
AB  - The ATP-sensitive potassium channel is made up of four pore forming Kir6.2
      subunits, surrounded by four regulatory sulphonylurea receptor (SUR) subunits.
      The latter subunit contains two nucleotide-binding folds (NBFs) that confer the
      ability on the channel to sense changes in the metabolic status ([ATP]/[ADP]) of
      the cell and couple the changes to the membrane potential of the cell. In an
      attempt to better understand the mechanisms by which NBFs influence the activity
      of the channel, we have expressed the NBF domains with C-terminally added
      epitopes (FLAG to NBF1 and His(6) to NBF2) in Escherichia coli and the rabbit
      reticulocyte lysate system and examined the ability of these domains to interact
      with each other and with Kir6.2. Both NBFs could be expressed to high levels in
      E. coli and purified to homogeneity from inclusion bodies. Re-folding of the
      proteins proved to be unsuccessful. However, we were able to obtain small amounts
      of radio-labelled NBFs in a soluble state. Using co-immunoprecipitation, we
      demonstrate that the radio-labelled NBF1 and NBF2 interact with each other.
      Neither of the NBFs bound to Kir6.2 expressed in the presence of canine
      microsomes.

PMID- 12054763
TI  - Potent inhibition of HIV-1 fusion by cyanovirin-N requires only a single high
      affinity carbohydrate binding site: characterization of low affinity carbohydrate
      binding site knockout mutants.
AB  - Cyanovirin-N (CVN) is a novel cyanobacterial protein that potently inhibits viral
      entry by human immunodeficiency viruses (HIV) via high affinity carbohydrate
      mediated binding to the surface envelope glycoprotein gp120. Bearing C(2) pseudo
      symmetry, CVN contains two carbohydrate binding sites of differing affinities
      located at opposite ends of the protein. CVN selectively binds with nanomolar
      affinity the mammalian high mannose oligosaccharides oligomannose-8 D1D3 and
      oligomannose-9, which also govern binding to gp120. At nanomolar concentrations
      CVN binds these oligosaccharides only through its high affinity site, while at
      micromolar to millimolar concentrations the oligosaccharides are bound through
      both sites leading to divalent protein-carbohydrate interactions. Similarly, two
      modes of binding to gp120 can be envisioned where CVN either binds gp120 solely
      through the high affinity site, or binds divalently using both carbohydrate
      binding sites. To determine the role of the low affinity site in binding to
      gp120, we sought to design a variant of CVN that lacks the low affinity
      carbohydrate binding site but retains a fully functional high affinity site.
      Thus, we constructed a series of CVN mutants possessing cumulative mutations in
      the low affinity site only, and characterized by NMR the overall structure and
      carbohydrate binding ability of each of these mutants. We demonstrate that
      carbohydrate binding by the low affinity site is completely absent in two mutants
      bearing three or four mutations (namely, m3-CVN=Lys3Asn, Glu23Ile, Asn93Ala; and
      m4-CVN=Lys3Asn, Thr7Ala, Glu23Ile, Asn93Ala), while the high affinity site binds
      the high affinity ligand Manalpha(1-2)Manalpha with a K(d) value equal to that
      measured for CVN. Using an HIV-1 cell fusion assay, we show that all of the
      mutants inhibit HIV-1 fusion with nearly identical IC50 values as wild-type CVN.
      We interpret these results as indicating that the low affinity carbohydrate
      binding site of CVN is not necessary for high affinity binding to gp120, and HIV
      1 fusion can therefore be blocked by monovalent protein-carbohydrate
      interactions.

PMID- 12054764
TI  - In vitro cleavage of eIF4GI but not eIF4GII by HIV-1 protease and its effects on
      translation in the rabbit reticulocyte lysate system.
AB  - In eukaryotic cells, protein synthesis is regulated by a set of initiation
      factors (eIF) that are required for recruiting the 40 S ribosomal subunit onto
      the mRNA molecule. Among these proteins, eIF4GI, which is targeted by
      picornaviral proteases, makes a bridge between the mRNA cap structure (via eIF4E)
      and the 40 S ribosome (via eIF3). Recently, internal ribosome entry segment
      (IRES) elements have been characterized in the genomic RNA of both simian
      immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1),
      suggesting that viral expression of these two viruses can be regulated at the
      translational level. Thus, by analogy with members of the picornavirus family, we
      have investigated the action of the HIV-1 protease on initiation factors eIF4GI
      and eIF4GII using cell extracts and the rabbit reticulocyte lysate system. Our
      results show that eIF4GI, but not eIF4GII, is substrate for HIV-1 protease and
      this effect can be prevented by a HIV-1 protease inhibitor, palinavir. However,
      in contrast to picornaviral proteases, the cleavage of eIF4GI by HIV-1 protease
      occurs at multiple sites and impairs translation of both cap-dependent and IRES
      containing RNAs, except for the HCV IRES, which does not require eIF4GI or
      eIF4GII for activity.

PMID- 12054765
TI  - Sub-proteome differential display: single gel comparison by 2D electrophoresis
      and mass spectrometry.
AB  - Two-dimensional (2D) gel electrophoresis and mass spectrometry (MS) have been
      used in comparative proteomics but inherent problems of the 2D electrophoresis
      technique lead to difficulties when comparing two samples. We describe a method
      (sub-proteome differential display) for comparing the proteins from two sources
      simultaneously. Proteins from one source are mixed with radiolabelled proteins
      from a second source in a ratio of 100:1. These combined proteomes are
      fractionated simultaneously using column chromatographic methods, followed by
      analysis of the pre-fractionated proteomes (designated sub-proteomes) using 2D
      gel electrophoresis. Silver staining and (35)S autoradiography of a single gel
      allows precise discrimination between members of each sub-proteome, using
      commonly available computer software. This is followed by MS identification of
      individual proteins. We have demonstrated the utility of the technology by
      identifying the product of a transfected gene and several proteins expressed
      differentially between two renal carcinoma proteomes. The procedure has the
      capacity to enrich proteins prior to 2D electrophoresis and provides a simple,
      inexpensive approach to compare proteomes. The single gel approach eliminates
      differences that might arise if separate proteome fractionations or 2D gels are
      employed.

PMID- 12054766
TI  - A general strategy for effector-mediated control of RNA-cleaving ribozymes and
      DNA enzymes.
AB  - A novel and general approach is described for generating versions of RNA-cleaving
      ribozymes (RNA enzymes) and DNAzymes (DNA enzymes), whose catalytic activity can
      be controlled by the binding of activator molecules. Variants of the RNA-cleaving
      10-23 DNAzyme and 8-17 DNAzyme were created, whose catalysis was activated by up
      to approximately 35-fold by the binding of the effector adenosine. The design of
      such variants was possible even though the tertiary folding of the two DNAzymes
      is not known. Variants of the hammerhead ribozyme were constructed, to respond to
      the effectors ATP and flavin mononucleotide. Whereas in conventional allosteric
      ribozymes, effector-binding modulates the chemical step of catalysis, here,
      effectors exercise their effect upon the substrate-binding step, by stabilizing
      the enzyme-substrate complex. Because such an approach for controlling the
      activity of DNAzymes/ribozymes requires no prior knowledge of the enzyme's
      secondary or tertiary folding, this regulatory strategy should be generally
      applicable to any RNA-cleaving ribozyme or DNAzyme, natural or in vitro selected,
      provided substrate-recognition is achieved by Watson-Crick base-pairing.

PMID- 12054767
TI  - A novel short peptide is a specific inhibitor of the human immunodeficiency virus
      type 1 integrase.
AB  - The retroviral encoded protein integrase (IN) is required for the insertion of
      the human immunodeficiency virus type 1 (HIV-1) proviral DNA into the host
      genome. In spite of the crucial role played by IN in the retroviral life cycle,
      which makes this enzyme an attractive target for the development of new anti-AIDS
      agents, very few inhibitors have been described and none seems to have a
      potential use in anti-HIV therapy. To obtain potent and specific IN inhibitors,
      we used the two-hybrid system to isolate short peptides. Using HIV-1 IN as a bait
      and a yeast genomic library as the source of inhibitory peptides (prey), we
      isolated a 33-mer peptide (I33) that bound tightly to the enzyme. I33 inhibited
      both in vitro IN activities, i.e. 3' end processing and strand transfer. Further
      analysis led us to select a shorter peptide, EBR28, corresponding to the N
      terminal region of I33. Truncated variants showed that EBR28 interacted with the
      catalytic domain of IN interfering with the binding of the DNA substrate. Alanine
      single substitution of each EBR28 residue (alanine scanning) allowed the
      identification of essential amino acids involved in the inhibition. The EBR28 NMR
      structure shows that this peptide adopts an alpha-helical conformation with
      amphipathic properties. Additionally, EBR28 showed a significant antiviral effect
      when assayed on HIV-1 infected human cells. Thus, this potentially important
      short lead peptide may not only be helpful to design new anti-HIV agents, but
      also could prove very useful in further studies of the structural and functional
      characteristics of HIV-1 IN.

PMID- 12054768
TI  - An ensemble of theta class glutathione transferases with novel catalytic
      properties generated by stochastic recombination of fragments of two mammalian
      enzymes.
AB  - The correlation between sequence diversity and enzymatic function was studied in
      a library of Theta class glutathione transferases (GSTs) obtained by stochastic
      recombination of fragments of cDNA encoding human GST T1-1 and rat GST T2-2. In
      all, 94 randomly picked clones were characterized with respect to sequence,
      expression level, and catalytic activity in the conjugation reactions between
      glutathione and six alternative electrophilic substrates. Out of these six
      different compounds, dichloromethane is a selective substrate for human GST T1-1,
      whereas 1-menaphthyl sulfate and 1-chloro-2,4-dinitrobenzene are substrates for
      rat GST T2-2. The other three substances serve as substrates for both enzymes.
      Through this broad characterization, we have identified enzyme variants that have
      acquired novel activity profiles that differ substantially from those of the
      original GSTs. In addition, the expression levels of many clones were improved in
      comparison to the parental enzyme. A library of mutants can thus display a
      distribution of properties from which highly divergent evolutionary pathways may
      emerge, resembling natural evolutionary processes. From the GST library, a clone
      was identified that, by the point mutation N49D in the rat GST T2-2 sequence, has
      a 1700% increased activity with 1-menaphthyl sulfate and a 60% decreased activity
      with 4-nitrophenethyl bromide. Through the N49D mutation, the ratio of these
      activities has thus been altered 40-fold. An extensive characterization of a
      population of stochastically mutated enzymes can accordingly be used to find
      variants with novel substrate-activity profiles and altered catalytic properties.
      Recursive recombination of selected sequences displaying optimized properties is
      a strategy for the engineering of proteins for medical and biochemical
      applications. Such sequential design is combinatorial protein chemistry based on
      remodeling of existing structural scaffolds and has similarities to evolutionary
      processes in nature.

PMID- 12054769
TI  - Computational identification of transcription factor binding sites via a
      transcription-factor-centric clustering (TFCC) algorithm.
AB  - While microarray-based expression profiling has facilitated the use of
      computational methods to find potential cis-regulatory promoter elements, few
      current in silico approaches explicitly link regulatory motifs with the
      transcription factors that bind them. We have thus developed a TF-centric
      clustering (TFCC) algorithm that may provide such missing information through
      incorporation of biological knowledge about TFs. TFCC is a semi-supervised
      clustering algorithm which relies on the assumption that the expression profiles
      of some TFs may be related to those of the genes under their control. We examined
      this premise and found the vicinities of TFs in expression space are often
      enriched with the genes they regulate. So, instead of clustering genes based on
      the mutual similarity of their expression profiles to each other, we used TFs as
      seeds to group together genes whose expression patterns correlate with that of a
      particular TF. Then a Gibbs sampling algorithm was applied to search for shared
      cis-regulatory elements in promoters of clustered genes. Our working hypothesis
      was that if a TF-centric cluster indeed contains many targets of the seeding TF,
      at least one of the discovered motifs would be the site bound by the very same
      TF. We tested the TFCC approach on eight cell cycle and sporulation regulating
      TFs whose binding sites have been previously characterized in Saccharomyces
      cerevisiae, and correctly identified binding site motifs for half of them. In
      addition, we also made de novo predictions for some unknown TF binding sites.

PMID- 12054770
TI  - A highly conserved lysine residue in phi29 DNA polymerase is important for
      correct binding of the templating nucleotide during initiation of phi29 DNA
      replication.
AB  - DNA polymerases that initiate replication by protein-priming are able to catalyze
      terminal protein (TP)-primed initiation, the following transition steps and
      finally DNA-primed elongation. Therefore, their structures must be able to
      position sequentially both primers, TP and DNA, at a common binding site. For DNA
      templated initiation, these DNA polymerases have to bind the origin of
      replication as template and TP as primer. It is likely that very precise
      interactions are required to position both TP and templating nucleotide at the
      polymerization active site. Such a specificity during TP-priming must rely on
      specific amino acids that must be evolutionarily conserved in this subfamily of
      DNA polymerases. By site-directed mutagenesis, we have analyzed the functional
      significance of Lys392 of phi29 DNA polymerase, immediately adjacent to the
      Kx3NSxYG motif, and specifically conserved among protein-primed DNA polymerases.
      During TP-primed initiation, mutations in this residue did not affect untemplated
      TP-dAMP formation, indicating that the interaction with the initiating nucleotide
      and TP were not affected, whereas the template-directed initiation activity was
      severely inhibited. Both mutant DNA polymerases had a wild-type-like (overall)
      DNA binding activity. We thus infer that residue Lys392 of phi29 DNA polymerase
      is important for the correct positioning of the templating nucleotide at the
      polymerization active site, a critical requirement during template-directed TP
      priming at phi29 DNA origins. Consequently, mutation of this residue compromised
      the fidelity of the initiation reaction, not controlled by the 3'-5' exonuclease
      activity. During DNA-primed polymerization, the mutant polymerases showed a
      defect in translocation of the template strand. This translocation problem could
      be the consequence of a more general defect in the stabilization and positioning
      of a next templating nucleotide at the polymerization active site, during DNA
      primed DNA synthesis.

PMID- 12054771
TI  - Abeta42-peptide assembly on lipid bilayers.
AB  - One of the major pathological features of Alzheimer's disease (AD) is the
      presence of extracellular amyloid plaques that are composed predominantly of the
      amyloid-beta peptide (Abeta). Diffuse plaques associated with AD are composed
      predominantly of Abeta42, whereas senile plaques contain both Abeta40 and
      Abeta42. Recently, it has been suggested that diffuse plaque formation is
      initiated as a plasma membrane-bound Abeta species and that Abeta42 is the
      critical component. In order to investigate this hypothesis, we have examined
      Abeta42-membrane interactions using in situ atomic force microscopy and
      fluorescence spectroscopy. Our studies demonstrate the association of Abeta42
      with planar bilayers composed of total brain lipids, which results initially in
      peptide aggregation and then fibre formation. Modulation of the cholesterol
      content is correlated with the extent of Abeta42-assembly on the bilayer surface.
      Although Abeta42 was not visualized directly on cholesterol-depleted bilayers,
      fluorescence anisotropy and fluorimetry demonstrate Abeta42-induced membrane
      changes. Our results demonstrate that the composition of the lipid bilayer
      governs the outcome of Abeta interactions.

PMID- 12054772
TI  - Domain closure, substrate specificity and catalysis of D-lactate dehydrogenase
      from Lactobacillus bulgaricus.
AB  - NAD-dependent Lactobacillus bulgaricus D-Lactate dehydrogenase (D-LDHb) catalyses
      the reversible conversion of pyruvate into D-lactate. Crystals of D-LDHb
      complexed with NADH were grown and X-ray data collected to 2.2 A. The structure
      of D-LDHb was solved by molecular replacement using the dimeric Lactobacillus
      helveticus D-LDH as a model and was refined to an R-factor of 20.7%. The two
      subunits of the enzyme display strong asymmetry due to different crystal
      environments. The opening angles of the two catalytic domains with respect to the
      core coenzyme binding domains differ by 16 degrees. Subunit A is in an "open"
      conformation typical for a dehydrogenase apo enzyme and subunit B is "closed".
      The NADH-binding site in subunit A is only 30% occupied, while in subunit B it is
      fully occupied and there is a sulphate ion in the substrate-binding pocket. A
      pyruvate molecule has been modelled in the active site and its orientation is in
      agreement with existing kinetic and structural data. On domain closure, a cluster
      of hydrophobic residues packs tightly around the methyl group of the modelled
      pyruvate molecule. At least three residues from this cluster govern the substrate
      specificity. Substrate binding itself contributes to the stabilisation of domain
      closure and activation of the enzyme. In pyruvate reduction, D-LDH can adapt
      another protonated residue, a lysine residue, to accomplish the role of the acid
      catalyst His296. Required lowering of the lysine pK(a) value is explained on the
      basis of the H296K mutant structure.

PMID- 12054773
TI  - Multiple oligomeric states of the Helicobacter pylori vacuolating toxin
      demonstrated by cryo-electron microscopy.
AB  - Helicobacter pylori vacuolating toxin (VacA) is a bacterial protein toxin that
      forms water-soluble oligomeric complexes, and can somehow insert into lipid
      bilayers to produce anion-selective channels. In this study, we utilize the novel
      technique of "cryo-negative staining" to examine the morphology of vitrified VacA
      complexes. Two basic types of oligomeric structures were observed: (i) relatively
      thick six or seven-sided astral arrays with near-perfect radial symmetry; and
      (ii) relatively thin astral arrays of six to nine short "rodlets" that display a
      distinct handedness or "chirality". Additionally, the new technique provided edge
      views of the thicker form of VacA oligomer, which appears to be a thin bilayered
      disc, indicating that the relatively thick six-sided arrays are actually
      dodecamers. Also observed occasionally in the present cryo-negatively stained
      VacA preparations were 2D crystalline arrays that appeared to be comprised of
      interlocked dodecamers. The structural alterations that VacA oligomers must
      undergo to form these 2D crystals were analyzed, and intermediates in this
      transition were identified. Additionally, the oligomeric state of acid-activated
      VacA bound to membranes was visualized by the traditional technique of "deep
      etch" electron microscopy, and was found to resemble most closely the top halves
      of the dodecamers. These results indicate that VacA is able to undergo major
      conformational changes, accompanied by major changes in its state of
      oligomerization, under different natural and experimental conditions.

PMID- 12054774
TI  - Crystal structure of the anti-His tag antibody 3D5 single-chain fragment
      complexed to its antigen.
AB  - The crystal structure of a mutant form of the single-chain fragment (scFv),
      derived from the monoclonal anti-His tag antibody 3D5, in complex with a
      hexahistidine peptide has been determined at 2.7 A resolution. The peptide binds
      to a deep pocket formed at the interface of the variable domains of the light and
      the heavy chain, mainly through hydrophobic interaction to aromatic residues and
      hydrogen bonds to acidic residues. The antibody recognizes the C-terminal
      carboxylate group of the peptide as well as the main chain of the last four
      residues and the last three imidazole side-chains. The crystals have a solvent
      content of 77% (v/v) and form 70 A-wide channels that would allow the diffusion
      of peptides or even small proteins. The anti-His scFv crystals could thus act as
      a framework for the crystallization of His-tagged target proteins. Designed
      mutations in framework regions of the scFv lead to high-level expression of
      soluble protein in the periplasm of Escherichia coli. The recombinant anti-His
      scFv is a convenient detection tool when fused to alkaline phosphatase. When
      immobilized on a matrix, the antibody can be used for affinity purification of
      recombinant proteins carrying a very short tag of just three histidine residues,
      suitable for crystallization. The experimental structure is now the basis for the
      design of antibodies with even higher stability and affinity.

PMID- 12054775
TI  - Functional interactions of nucleocapsid protein of feline immunodeficiency virus
      and cellular prion protein with the viral RNA.
AB  - All lentiviruses and oncoretroviruses examined so far encode a major nucleic-acid
      binding protein (nucleocapsid or NC* protein), approximately 2500 molecules of
      which coat the dimeric RNA genome. Studies on HIV-1 and MoMuLV using in vitro
      model systems and in vivo have shown that NC protein is required to chaperone
      viral RNA dimerization and packaging during virus assembly, and proviral DNA
      synthesis by reverse transcriptase (RT) during infection. The human cellular
      prion protein (PrP), thought to be the major component of the agent causing
      transmissible spongiform encephalopathies (TSE), was recently found to possess a
      strong affinity for nucleic acids and to exhibit chaperone properties very
      similar to HIV-1 NC protein in the HIV-1 context in vitro. Tight binding of PrP
      to nucleic acids is proposed to participate directly in the prion disease
      process. To extend our understanding of lentiviruses and of the unexpected
      nucleic acid chaperone properties of the human prion protein, we set up an in
      vitro system to investigate replication of the feline immunodeficiency virus
      (FIV), which is functionally and phylogenetically distant from HIV-1. The results
      show that in the FIV model system, NC protein chaperones viral RNA dimerization,
      primer tRNA(Lys,3) annealing to the genomic primer-binding site (PBS) and minus
      strand DNA synthesis by the homologous FIV RT. FIV NC protein is able to trigger
      specific viral DNA synthesis by inhibiting self-priming of reverse transcription.
      The human prion protein was found to mimic the properties of FIV NC with respect
      to primer tRNA annealing to the viral RNA and chaperoning minus strand DNA
      synthesis.

PMID- 12054776
TI  - On the role of electrostatic interactions in the design of protein-protein
      interfaces.
AB  - Here, the methods of continuum electrostatics are used to investigate the
      contribution of electrostatic interactions to the binding of four protein-protein
      complexes; barnase-barstar, human growth hormone and its receptor, subtype N9
      influenza virus neuraminidase and the NC41 antibody, the Ras binding domain (RBD)
      of kinase cRaf and a Ras homologue Rap1A. In two of the four complexes
      electrostatics are found to strongly oppose binding (hormone-receptor and
      neuraminidase-antibody complexes), in one case the net effect is close to zero
      (barnase-barstar) and in one case electrostatics provides a significant driving
      force favoring binding (RBD-Rap1A). In order to help understand the wide range of
      electrostatic contributions that were calculated, the electrostatic free energy
      was partitioned into contributions of individual charged and polar residues, salt
      bridges and networks involving salt bridges and hydrogen bonds. Although there is
      no one structural feature that accounts for the differences between the four
      interfaces, the extent to which the desolvation of buried charges is compensated
      by the formation of hydrogen bonds and ion pairs appears to be an important
      factor. Structural features that are correlated with contribution of an
      individual residue to stability are also discussed. These include partial burial
      of a charged group in the free monomer, the formation of networks involving
      charged and polar amino acids, and the formation of partially exposed ion-pairs.
      The total electrostatic contribution to binding is found to be inversely
      correlated with buried total and non-polar surface area. This suggests that
      different interfaces can be designed to exploit electrostatic and hydrophobic
      forces in very different ways.

PMID- 12054777
TI  - Crystal structure of the V-region of Streptococcus mutans antigen I/II at 2.4 A
      resolution suggests a sugar preformed binding site.
AB  - Antigens I/II are large multifunctional adhesins from oral viridans streptococci
      that exert immunomodulatory effects on human cells and play important roles in
      inflammatory disorders. Among them, Streptococcus mutans plays a major role in
      the initiation of dental caries. The structure of the V-region (SrV+, residues
      464-840) of the antigen I/II of S. mutans has been determined using the
      multiwavelength anomalous diffraction phasing technique with seleno-methionine
      substituted recombinant protein and subsequently refined at 2.4 A resolution. The
      crystal structure of SrV+ revealed a lectin-like fold that displays a putative
      preformed carbohydrate-binding site stabilized by a metal ion. Inhibition of this
      binding site may confer to humans a protection against dental caries and
      dissemination of the bacteria to extra-oral sites involved in life-threatening
      inflammatory diseases. This crystal structure constitutes a first step in
      understanding the structure-function relationship of antigens I/II and may help
      in delineating new preventive or therapeutic strategies against colonization of
      the host by oral streptococci.

PMID- 12054779
TI  - Application of the diffusion-collision model to the folding of three-helix bundle
      proteins.
AB  - The diffusion-collision model has been successful in explaining many features of
      protein folding kinetics, particularly for helical proteins. In the model the
      folding reaction is described in terms of coupled chemical kinetic (Master)
      equations of coarse grained entities, called microdomains. Here, the diffusion
      collision model is applied to compute the folding kinetics of four three-helix
      bundle proteins, all of which fold on a time scale of tens of microseconds and
      appear to have two-state folding. The native structure and the stability of the
      helical microdomains are used to determine the parameters of the model. The
      formulation allows computation of the overall rate and determination of the
      importance of kinetic intermediates. The proteins considered are the B domain of
      protein A (1BDC), the Engrailed Homeodomain (1ENH), the peripheral sub-unit
      binding domain (1EBD C-chain) and the villin headpiece subdomain (1VII). The
      results for the folding time of protein A, the Engrailed Homeodomain, and 1EBD C
      chain are in agreement with experiment, while 1VII is not stable in the present
      model. In the three proteins that are stable, two-state folding is predicted by
      the diffusion-collision model. This disagrees with published assertions that
      multistate kinetics would be obtained from the model. The contact order
      prediction agrees with experiment for protein A, but yields values that are a
      factor of 40, 30 and 15 too slow for 1ENH, 1EBD C-chain and 1VII. The effect of
      mutants on folding is described for protein A and it is demonstrated that
      significant intermediate concentrations (i.e. deviation from two-state folding)
      can occur if the stability of some of the helical microdomains is increased. A
      linear relationship between folding time and the length of the loop between
      helices B and C in protein A is demonstrated; this is not evident in the contact
      order description.

PMID- 12054781
TI  - Shell disease in eastern oysters, Crassostrea virginica, reared in France.
AB  - Progeny of eastern oyster, Crassostrea virginica, introduced into France in 1992,
      were reared in IFREMER facilities to test their growth performances. During the
      summer of 1993, sporadic mass mortalities (80-90%) occurred among C. virginica
      spat reared in the IFREMER laboratories in La Tremblade (Charente Maritime,
      France) and Bouin (Vendee, France). Affected oysters presented mantle retraction
      and deposition of an anomalous conchiolin layer on the inner surface of the
      shell. The incidence of oysters with gross signs exceeded 80%. No obvious
      pathogen was identified in soft tissues by histology and transmission electron
      microscopy (TEM). However, histological examination showed the presence of
      anomalous basophilic round structures, 0.5-1 microm in diameter, in gill and
      mantle connective tissues. These extracellular Feulgen-negative structures
      reacted positively with the von Kossa stain. TEM examination on mantle and gill
      samples in diseased spat showed that the basophilic bodies consisted of
      concentric deposits of an amorphous substance interpreted as containing calcium.
      These observations may indicate that the mineralization process in spat shells
      was disturbed without exact determination of the cause. Based on the similarities
      of the gross signs to those reported in juvenile eastern oysters in the United
      States, we believe that the cause of the mortalities observed in France was
      probably the Juvenile Oyster Disease. Moreover, we report for the first time the
      detection of anomalous amorphous structures in gill and mantle connective tissues
      associated with mortalities and deposition of an anomalous conchioloin layer on
      the inner shell surface in C. virginica spat.

PMID- 12054778
TI  - The crystal structure of a major dust mite allergen Der p 2, and its biological
      implications.
AB  - The crystal structure of the common house mite (Dermatophagoides sp.) Der p 2
      allergen was solved at 2.15 A resolution using the MAD phasing technique, and
      refined to an R-factor of 0.209. The refined atomic model, which reveals an
      immunoglobulin-like tertiary fold, differs in important ways from the previously
      described NMR structure, because the two beta-sheets are significantly further
      apart and create an internal cavity, which is occupied by a hydrophobic ligand.
      This interaction is structurally reminiscent of the binding of a prenyl group by
      a regulatory protein, the Rho guanine nucleotide exchange inhibitor. The crystal
      structure suggests that binding of non-polar molecules may be essential to the
      physiological function of the Der p 2 protein.

PMID- 12054782
TI  - Storage stability of Anagrapha falcifera nucleopolyhedrovirus in spray-dried
      formulations.
AB  - A multiply embedded nucleopolyhedrovirus isolated from Anagrapha falcifera
      (Kirby) (AfMNPV) can lose insecticidal activity during months of dry storage in
      ambient room conditions. We tested the spray-dried AfMNPV formulations after
      storage for up to 1 year at room temperatures for insecticidal activity against
      neonate Trichoplusia ni (Hubner). Experimental formulations were made using
      combinations of corn flours, lignin, and sucrose, and were selected based on
      previous work which demonstrated that these formulations resisted solar
      degradation in field experiments. Twelve experimental formulations (organized in
      three groups of four formulations) compared the effect of (1) the ratio of
      formulation ingredients (lignin and corn flour) to virus concentration, (2)
      different sources of lignin, or (3) different corn flours and sugar. Based on a
      single-dose plant assay with these 12 formulations, none of the formulations lost
      significant activity due to the drying process, when compared with the
      unformulated wet AfMNPV. Samples of the 12 dried formulations were stored at room
      (22+/-3 degrees C) and refrigerated (4 degrees C) temperatures. Insecticidal
      activity (LC(50)) was determined with a dosage-response assay for neonates fed on
      treated cotton-leaf disks. After 6 (or 9) and 12 months storage, refrigerated
      samples maintained insecticidal activity better than corresponding samples stored
      at room temperatures with LC(50)s that averaged 2.0 x 10(6) polyhedral inclusion
      bodies per milliliter (pibs/ml) for refrigerated samples and 5.4 x 10(6) pibs/ml
      for samples stored at room temperatures. Compared with unformulated stock virus
      stored frozen, six formulations stored at room temperature and 10 formulations
      stored in the refrigerator did not lose significant insecticidal activity after 1
      year based on overlapping 90% confidence intervals. Changing the ratio of virus
      to formulation ingredients did not provide a clear trend over the range of
      concentrations tested, and may be less important for shelf-life of virus activity
      compared with formulations made with different ingredients. Two of the four
      formulations made with different lignins were about 15 times less active after 1
      year at room temperature compared with refrigerated samples, indicating that
      specific formulation ingredients can affect storage stability. Formulations that
      contained sugar generally maintained activity during storage better than
      formulations without sugar. Unformulated virus stock maintained insecticidal
      activity (ranged from 0.20 to 2.5 x 10(6) pibs/ml) better during storage than
      dried formulations with LC(50)s that ranged from 0.39 to 27 x 10(6) pibs/ml.
      Unformulated virus stock, which is essentially a suspension of virus occlusion
      bodies in homogenized insect cadavers, did not lose activity when stored at
      refrigerated or room temperature. We believe that stability of AfMNPV
      insecticidal activity during storage as dry formulations is related to the
      general composition of the formulation and that sugar may play a critical role in
      maintaining insecticidal activity.

PMID- 12054783
TI  - Early developmental stages of two actinosporeans, Raabeia and Aurantiactinomyxon
      (Myxozoa), as detected by light and electron microscopy.
AB  - The development of actinosporeans in their oligochaete host proceeding
      pansporocyst formation is relatively well documented, however, phases preceding
      it are not as well known. The initial stages in the development of two
      actinosporeans, Raabeia type 1 of Oumouna et al. [Parasitol. Res. 2002] and
      Aurantiactinomyxon pavinsis (Ormieres, 1968) Marques [Languedoc, Universite des
      Sciences et Techniques, Dissertation, 1984] from schizogony to gametogony and
      sporogony are described. Both actinosporeans begin their development as
      multinucleate stages near the basal lamina of the oligochaete intestine. Proximal
      to these stages and between the host epithelium cells are uninucleate cells whose
      nuclei divide to produce binucleate cells. These divide mitotically to produce
      cells with four nuclei which then undergo plasmotomy to yield a tetracellular
      stage and the first phase in pansporocyst formation. From the uninucleate stage
      to the tetranucleate stage, the cell membrane of the parasite is associated
      closely via finger-like projections with the intestinal epithelial and glandular
      cells of the host.

PMID- 12054784
TI  - The life cycle of Gregarina ronderosi n. sp. (Apicomplexa: Gregarinidae) in the
      Argentine grasshopper Dichroplus elongatus (Orthoptera: Acrididae).
AB  - Gregarina ronderosi n. sp. is described based on life cycle observations
      conducted on nymphs and adults of its natural host, the grasshopper Dichroplus
      elongatus. Following ingestion of oocysts by the host, parasite development
      occurs between the epithelium and the food mass in the midgut and gastric caeca.
      Gametocysts are liberated in the faeces. Natural prevalence in the type locality,
      Girondo, northwestern Buenos Aires Province, was 39.7% (n=131). The earliest
      trophozoites seen were small (< or = 10 microm), somewhat ovoid, unsegmented
      bodies. Fully developed trophozoites (the body is divided into epimerite,
      protomerite, and deutomerite) were slender, with conical or globular epimerites
      in attached or unattached forms, respectively. Trophozoites varied greatly in
      size [total length: 10.4-275.1 microm; mean (+/-S.E.): 126.3+/-78.9]. Gamonts,
      which were the most common stages observed and filled the midgut and gastric
      caeca in grasshoppers kept in rearing rooms, had a stocky appearance and also
      varied greatly in size (total length: 80-348 microm; 205+/-13). Association of
      gamonts was precocious, biassociative, and caudofrontal. Gametocysts were
      spherical and highly variable in size (96-376 microm in diameter; 202.8+/-52.5),
      and normally have 14 sporoduct basal discs. Everted sporoducts were up to 60
      microm long. Oocysts were uniformly doliform in shape, measured (5+/-0.08 by
      3.2+/-0.06 microm) and contained eight sporozoites. Wall reinforcements (carinae)
      were present. No infection resulted in experimentally inoculated Locusta
      migratoria, which is a host of Gregarina acridiorum. G. ronderosi is strikingly
      similar to G. acridiorum, but has larger oocysts.

PMID- 12054785
TI  - Deposition and germination of conidia of the entomopathogen Entomophaga maimaiga
      infecting larvae of gypsy moth, Lymantria dispar.
AB  - Germination of conidia of Entomophaga maimaiga, an important fungal pathogen of
      gypsy moth, Lymantria dispar, was investigated on water agar and larval cuticle
      at varying densities. Percent germination was positively associated with conidial
      density on water agar but not on larval cuticle. When conidia were showered onto
      water agar, the rate of germination was much slower than on the cuticle of L.
      dispar larvae. From the same conidial showers, the resulting conidial densities
      on water agar were much higher than those on larval cuticle in part because many
      conidia adhered to setae and did not reach the cuticle. A second factor
      influencing conidial densities on larval cuticle was the location conidia
      occurred on larvae. Few conidia were found on the flexible intersegmental
      membranes in comparison with the areas of more rigid cuticle, presumably because
      conidia were physically dislodged from intersegmental membranes when larvae
      moved. Conidia were also exposed to heightened CO(2) to evaluate whether this
      might influence germination. When conidia on water agar were exposed to
      heightened CO(2) levels, germinating conidia primarily formed germ tubes while
      most conidia exposed to ambient CO(2) rapidly formed secondary conidia.

PMID- 12054786
TI  - Vertical transmission of TnSNPV, TnCPV, AcMNPV, and possibly recombinant NPV in
      Trichoplusia ni.
AB  - Four viruses were tested for vertical transmission in Trichoplusia ni: T. ni
      nucleopolyhedrovirus (TnSNPV), T. ni cypovirus (TnCPV), Autographa californica
      nucleopolyhedrovirus (AcMNPV), and AcMNPV engineered to express a scorpion toxin
      (AcMNPV.AaIT). Fifth instars were exposed to each virus, the survivors were
      reared and mated, and second-generation (F(1)) insects were examined for
      infection. TnSNPV was transmitted to offspring at a prevalence rate of 15.4%,
      TnCPV at 10.2%, and AcMNPV at 10.1%. Only one of 2484 F(1) insects was infected
      with AcMNPV.AaIT; this experiment was repeated, and none of 4774 insects was
      infected. Thus, vertical transmission is unlikely to contribute to AcMNPV.AaIT
      contacting non-target organisms after its field release. There was evidence that
      TnCPV and possibly TnSNPV were activated to overt infections by ingestion of a
      different virus. TnCPV, but not the NPVs, routinely infected 0.3-1.7% of non
      treated insects, probably indicating that it is vertically transmitted at
      enzootic levels.

PMID- 12054787
TI  - Matrix assisted laser desorption ionisation time of flight mass spectrometry
      (MALDI-TOF MS) for detecting novel Bt toxins.
AB  - Matrix assisted laser desorption ionisation time of flight mass spectrometry
      (MALDI-TOF MS) was used to study crystal (Cry) toxins from different Bacillus
      thuringiensis (Bt) strains. Known Cry toxins such as Cry1Ac and Cry2A, as well as
      novel toxins for which the protein sequences were predicted by their gene
      sequences, were used as controls in this study. The peptide masses, obtained
      after in-gel trypsin digestion for all these proteins, matched correctly to the
      corresponding proteins. Also, MALDI-TOF MS was able to resolve and identify
      multiple Cry toxins of very similar molecular weights and highly similar
      isoelectric points, from a single protein band. Furthermore, in novel Bt strains
      for which PCR techniques were unable to detect the cognate genes, this method was
      able to detect novel Cry toxins. Hence, present data clearly suggest that MALDI
      TOF MS could be used as a tool for identifying Cry toxins from novel Bt strains.

PMID- 12054788
TI  - Further evidence that spindles of an entomopoxvirus enhance its infectivity in a
      host insect.

PMID- 12054789
TI  - Upregulation of transcripts encoding select heat shock proteins in the flesh fly
      Sarcophaga crassipalpis in response to venom from the ectoparasitoid wasp Nasonia
      vitripennis.

PMID- 12054791
TI  - Sequence conservation in Ig-like domains: the role of highly conserved proline
      residues in the fibronectin type III superfamily.
AB  - The role of conserved proline residues in fibronectin type III (fnIII) domains is
      investigated. Surprisingly, none of the standard set of explanations for residue
      conservation applies. The proline residues are not apparently conserved for
      function, or stability, or to nucleate folding, or to promote stabilising
      interactions across domain boundaries. However, when the most highly conserved
      proline residues are mutated to alanine there is an increase in the rate of
      aggregation of a fnIII double-module construct. The results suggest that proline
      residues may be conserved at domain-domain boundaries in fnIII domains to prevent
      aggregation in multi-modular proteins.

PMID- 12054792
TI  - Intrinsic membrane targeting of the flagellar export ATPase FliI: interaction
      with acidic phospholipids and FliH.
AB  - The specialised ATPase FliI is central to export of flagellar axial protein
      subunits during flagellum assembly. We establish the normal cellular location of
      FliI and its regulatory accessory protein FliH in motile Salmonella typhimurium,
      and ascertain the regions involved in FliH(2)/FliI heterotrimerisation. Both FliI
      and FliH localised to the cytoplasmic membrane in the presence and in the absence
      of proteins making up the flagellar export machinery and basal body. Membrane
      association was tight, and FliI and FliH interacted with Escherichia coli
      phospholipids in vitro, both separately and as the preformed FliH(2)/FliI
      complex, in the presence or in the absence of ATP. Yeast two-hybrid analysis and
      pull-down assays revealed that the C-terminal half of FliH (H105-235) directs
      FliH homodimerisation, and interacts with the N-terminal region of FliI (I1-155),
      which in turn has an intra-molecular interaction with the remainder of the
      protein (I156-456) containing the ATPase domain. The FliH105-235 interaction with
      FliI was sufficient to exert the FliH-mediated down-regulation of ATPase
      activity. The basal ATPase activity of isolated FliI was stimulated tenfold by
      bacterial (acidic) phospholipids, such that activity was 100-fold higher than
      when bound by FliH in the absence of phospholipids. The results indicate
      similarities between FliI and the well-characterised SecA ATPase that energises
      general protein secretion. They suggest that FliI and FliH are intrinsically
      targeted to the inner membrane before contacting the flagellar secretion
      machinery, with both FliH105-235 and membrane phospholipids interacting with FliI
      to couple ATP hydrolysis to flagellum assembly.

PMID- 12054793
TI  - Modulation of eukaryotic mRNA stability via the cap-binding translation complex
      eIF4F.
AB  - Decapping by Dcp1 in Saccharomyces cerevisiae is a key step in mRNA degradation.
      However, the cap also binds the eukaryotic initiation factor (eIF) complex 4F and
      its associated proteins. Characterisation of the relationship between decapping
      and interactions involving eIF4F is an essential step towards understanding
      polysome disassembly and mRNA decay. Three types of observation suggest how
      changes in the functional status of eIF4F modulate mRNA stability in vivo. First,
      partial disruption of the interaction between eIF4E and eIF4G, caused by
      mutations in eIF4E or the presence of the yeast 4E-binding protein p20,
      stabilised mRNAs. The interactions of eIF4G and p20 with eIF4E may therefore act
      to modulate the decapping process. Since we also show that the in vitro decapping
      rate is not directly affected by the nature of the body of the mRNA, this
      suggests that changes in eIF4F structure could play a role in triggering
      decapping during mRNA decay. Second, these effects were seen in the absence of
      extreme changes in global translation rates in the cell, and are therefore
      relevant to normal mRNA turnover. Third, a truncated form of eIF4E (Delta196) had
      a reduced capacity to inhibit Dcp1-mediated decapping in vitro, yet did not
      change cellular mRNA half-lives. Thus, the accessibility of the cap to Dcp1 in
      vivo is not simply controlled by competition with eIF4E, but is subject to
      switching between molecular states with different levels of access.

PMID- 12054794
TI  - A compact RNA tertiary structure contains a buried backbone-K+ complex.
AB  - The structure of a 58 nucleotide ribosomal RNA fragment buries several phosphate
      groups of a hairpin loop within a large tertiary core. During refinement of an X
      ray crystal structure containing this RNA, a potassium ion was found to be
      contacted by six oxygen atoms from the buried phosphate groups; the ion is
      contained completely within the solvent-accessible surface of the RNA. The
      electrostatic potential at the ion chelation site is unusually large, and more
      than compensates for the substantial energetic penalties associated with partial
      dehydration of the ion and displacement of delocalized ions. The very large
      predicted binding free energy, approximately -30 kcal/mol, implies that the site
      must be occupied for the RNA to fold. These findings agree with previous studies
      of the ion-dependent folding of tertiary structure in this RNA, which concluded
      that a monovalent ion was bound in a partially dehydrated environment where Mg2+
      could not easily compete for binding. By compensating the unfavorable free energy
      of buried phosphate groups with a chelated ion, the RNA is able to create a
      larger and more complex tertiary fold than would be possible otherwise.

PMID- 12054795
TI  - Sequence-specific and non-specific binding of the Rci protein to the asymmetric
      recombination sites of the R64 shufflon.
AB  - Specific cleavages within the shufflon-specific recombination site of plasmid R64
      were detected by primer extension when a DNA fragment carrying the recombination
      site was incubated with the shufflon-specific Rci recombinase. Rci-dependent
      cleavages occurred in the form of a 5' protruding 7 bp staggered cut, suggesting
      that DNA cleavage and rejoining in the shufflon system take place at these
      positions. As a result, shufflon crossover sites were designated as sfx sequences
      consisting of a central 7 bp spacer sequence, and left and right 12 bp arms. R64
      sfx sequences are unique among various site-specific recombination sites, since
      only the spacer sequence and the right arm sequence are conserved among various
      R64 sfxs, whereas the left arm sequence is not conserved and is not related to
      the right arm sequence. From nuclease protection analyses, Rci protein was shown
      to bind to entire R64 and artificial sfx sequences, suggesting that one Rci
      molecule binds to the conserved sfx right arm in a sequence-specific manner and
      the second to the sfx left arm in a non-specific manner. The sfx left arm
      sequences as well as the right arm sequences were shown to determine affinity to
      Rci and subsequently inversion frequency. Asymmetry of the sfx sequence may be
      the reason why Rci protein acts only on the inverted sfx sequences.

PMID- 12054796
TI  - Inhibition mechanism of cytokine activity of human autocrine motility factor
      examined by crystal structure analyses and site-directed mutagenesis studies.
AB  - Autocrine motility factor (AMF), a tumor-secreted cytokine, stimulates cell
      migration in vitro and metastasis in vivo. AMF is genetically identical with the
      extracellular cytokines neuroleukin (NLK) and maturation factor (MF) and,
      interestingly, the intracellular enzyme phosphohexose isomerase (PHI). The
      crystal structures of the inhibitor-free open form and the inhibitor (erythrose 4
      phosphate, E4P, a strong inhibitor of AMF's cytokine activity)-bound closed form
      of human AMF have been determined at 1.9 A and 2.4 A resolution, respectively.
      Upon E4P binding, local conformation changes (open to closed) occur around the
      inhibitor-binding site. The E4P-bound structure shows that the location of the
      inhibitor (of cytokine activity) binding site of human AMF is very similar to
      those of the inhibitor (of enzymatic activity) binding sites of PHIs. The present
      study shows clearly that there is structural overlap of the regions responsible
      for the enzymatic and cytokine functions of AMF and PHI and suggests two
      scenarios for the inhibition mechanism of cytokine activity of AMF by the
      carbohydrate phosphate group. One likely scenario is that the compound could
      compete for AMF binding with the carbohydrate moiety of the AMF receptor (AMFR),
      which is a glycosylated seven-transmembrane helix protein. The other scenario is
      that the local conformation changes upon inhibitor binding may affect the AMF
      AMFR interactions. To examine roles of the residues in the inhibitor-binding
      site, two mutant AMFs were prepared. Replacements of His389, which is hydrogen
      bonded to the hydroxyl group of E4P by Phe, and Thr215, which is hydrogen-bonded
      to the phosphate group of E4P by Asp, result in mutant AMFs that are impaired in
      cytokine activity. These results suggest a role for these amino acids in
      recognition of a carbohydrate moiety of the AMFR. Since the E4P is one of the
      smallest compounds having AMF inhibitor activity, knowledge of the present
      crystal structure would provide an insight into the lead compound design of more
      effective AMF inhibitors.

PMID- 12054797
TI  - Mass determination of native smooth muscle myosin filaments by scanning
      transmission electron microscopy.
AB  - The thick filaments of vertebrate smooth muscle have a fundamentally different
      arrangement of myosin molecules from the bipolar, helical organization present in
      striated muscle filaments. This side-polar, non-helical structure is probably
      critical to the ability of smooth muscles to shorten by large amounts; however,
      details of myosin organization beyond this general description are unknown. The
      non-helical arrangement of myosin precludes the use of helical reconstruction
      methods for structural determination, and a tomographic approach is required. As
      a first step towards this goal we have determined the number of myosin molecules
      present at each 14.5 nm repeat in native smooth muscle myosin filaments by
      scanning transmission electron microscopy. The mass-per-length of myosin
      filaments was 159 kDa/nm, corresponding to 4.38(+/-0.11) (mean+/-s.e.m.) myosin
      molecules at each 14.5 nm level. The mass of thin filaments in the preparation
      (intrinsic control) was 21 kDa/nm, consistent with current models of smooth
      muscle thin filament structure, and the mass of tobacco mosaic virus (mass
      standard) was within 5% of the known value. We conclude that native smooth muscle
      myosin filaments contain four myosin molecules at each 14.5 nm level, two on each
      side of the side-polar structure.

PMID- 12054798
TI  - The X-ray crystallographic structure of the angiogenesis inhibitor angiostatin.
AB  - Angiogenesis inhibitors have gained much public attention recently as anti-cancer
      agents and several are currently in clinical trials, including angiostatin (Phase
      I, Thomas Jefferson University Hospital, Philadelphia, PA). We report here the
      bowl-shaped structure of angiostatin kringles 1-3, the first multi-kringle
      structure to be determined. All three kringle lysine-binding sites contain a
      bound bicine molecule of crystallization while the former of kringle 2 and
      kringle 3 are cofacial. Moreover, the separation of the kringle 2 and kringle 3
      lysiner binding sites is sufficient to accommodate the alpha-helix of the 30
      residue peptide VEK-30 found in the kringle 2/VEK-30 complex. Together the three
      kringles produce a central cavity suggestive of a unique domain where they may
      function in concert.

PMID- 12054799
TI  - Substrate binding induces domain movements in orotidine 5'-monophosphate
      decarboxylase.
AB  - Orotidine 5'-monophosphate decarboxylase (ODCase) catalyses the decarboxylation
      of orotidine 5'-monophosphate to uridine 5'-monophosphate (UMP). We have earlier
      determined the structure of ODCase from Escherichia coli complexed with the
      inhibitor 1-(5'-phospho-beta-d-ribofuranosyl)barbituric acid (BMP); here we
      present the 2.5 A structure of the uncomplexed apo enzyme, determined from
      twinned crystals. A structural analysis and comparison of the two structures of
      the E. coli enzyme show that binding of the inhibitor is accompanied by
      significant domain movements of approximately 12 degrees around a hinge that
      crosses the active site. Hence, the ODCase dimer, which contains two active
      sites, may be divided in three domains: a central domain that is fixed, and two
      lids which independently move 12 degrees upon binding. Corresponding analyses,
      presented herein, of the two Saccharomyces cerevisiae ODCase structures (with and
      without BMP) and the Methanobacterium thermoautotrophicum ODCase structures (with
      and without 6-aza UMP) show very similar, but somewhat smaller domain movements.
      The domain movements seem to be initiated by the phosphoryl binding to the enzyme
      and can explain why the binding of the phosphoryl group is essential for the
      catalytic function.

PMID- 12054800
TI  - Leucine-induced dissociation of Escherichia coli Lrp hexadecamers to octamers.
AB  - Lrp is a global regulator of metabolism in Escherichia coli that helps cells
      respond to changes in environmental conditions. The action of Lrp as a
      transcriptional activator or repressor is sometimes affected when the medium
      contains exogenous leucine. In this study, we examined the thermodynamics of
      leucine binding to Lrp and to a leucine response mutant, Lrp-1, and leucine
      induced dissociation of Lrp hexadecamer to leucine-bound octamer. The results of
      dynamic light-scattering and fluorescence measurements suggest that Lrp has two
      leucine-binding sites, one a high-affinity site and the other a low-affinity site
      that is coupled to the dissociation reaction. The Gibbs free energy change for
      leucine binding to the high-affinity site is about -7.0 kcal/mol. Binding of two
      leucine molecules to low-affinity sites on the hexadecamer or one leucine
      molecule to one octamer induces the dissociation of hexadecamer to leucine-bound
      octamer. The Gibbs free energy change for leucine binding to the low-affinity
      site was estimated to be in the range -4.66 to -5.03 kcal/mol for leucine binding
      to an octamer or -6.01 to -6.75 kcal/mol for leucine binding to a hexadecamer.
      The thermodynamic parameters derived from this study were used together with
      other data to estimate the distribution of free Lrp hexadecamer, octamer, leucine
      bound hexadecamer, and leucine-bound octamer in cells. Mathematical modeling,
      employed to simulate modulation of Lrp action in response to growth conditions,
      gave results that are consistent with known patterns of Lrp action on different
      operons.

PMID- 12054801
TI  - The ligand-binding site of bovine beta-lactoglobulin: evidence for a function?
AB  - Ever since the fortuitous observation that beta-lactoglobulin (beta-Lg), the
      major whey protein in the milk of ruminants, bound retinol, the details of the
      binding have been controversial. beta-Lg is a lipocalin, like plasma retinol
      binding protein, so that ligand association was expected to make use of the
      central cavity in the protein. However, an early crystallographic analysis and
      some of the more recent solution studies indicated binding elsewhere. We have now
      determined the crystal structures of the complexes of the trigonal form of beta
      Lg at pH 7.5 with bound retinol (R=21.4% for 7329 reflections between 20 and 2.4
      A resolution, R(free)=30.6%) and with bound retinoic acid (R=22.7% for 7813
      reflections between 20 and 2.34 A resolution, R(free)=29.8%). Both ligands are
      found to occupy the central calyx in a manner similar to retinol binding in
      retinol-binding protein. We find no evidence of binding at the putative external
      binding site in either of these structural analyses. Further, competition between
      palmitic acid and retinol reveals only palmitate bound to the protein. An
      explanation is provided for the lack of ligand binding to the orthorhombic
      crystal form also obtained at pH 7.5. Finally, the possible function of beta-Lg
      is discussed in the light of its species distribution and similarity to other
      lipocalins.

PMID- 12054802
TI  - Conformational changes during the catalytic cycle of gluconate kinase as revealed
      by X-ray crystallography.
AB  - The crystal structure of gluconate kinase from Escherichia coli has been
      determined to 2.0 A resolution by X-ray crystallography. The three-dimensional
      structure was solved by multi-wavelength anomalous dispersion, using a crystal of
      selenomethionine-substituted enzyme. Gluconate kinase is an alpha/beta structure
      consisting of a twisted parallel beta-sheet surrounded by alpha-helices with
      overall topology similar to nucleoside monophosphate (NMP) kinases, such as
      adenylate kinase. In order to identify residues involved in substrate binding and
      catalysis, structures of binary complexes with ATP, the ATP analogue adenosine 5'
      (beta,gamma-methylene) triphosphate and the product, gluconate-6-phosphate have
      been determined. Significant conformational changes are induced upon binding of
      ATP to the enzyme. The largest changes involve a hinge-bending motion of the
      NMP(bind) part and a motion of the LID with adjacent helices, which opens the
      cavity to the second substrate, gluconate. Opening of the active site cleft upon
      ATP binding is the opposite of what has been observed in the NMP kinase family so
      far, which usually close their active site to prevent fortuitous hydrolysis of
      ATP. The conformational change positions the side-chain of Arg120 to stack with
      the purine ring of ATP and the side-chain of Arg124 is shifted to interact with
      the alpha-phosphate in ATP, at the same time protecting ATP from solvent water.
      The beta and gamma-phosphate groups of ATP bind in the predicted P-loop. A
      conserved lysine side-chain interacts with the gamma-phosphate group, and might
      promote phosphoryl transfer. Gluconate-6-phosphate binds with its phosphate group
      in a similar position as the gamma-phosphate of ATP, consistent with inline
      phosphoryl transfer. The gluconate binding-pocket in GntK is located in a
      different position than the nucleoside binding-site usually found in NMP kinases.

PMID- 12054803
TI  - The structure of arylamine N-acetyltransferase from Mycobacterium smegmatis--an
      enzyme which inactivates the anti-tubercular drug, isoniazid.
AB  - Arylamine N-acetyltransferases which acetylate and inactivate isoniazid, an anti
      tubercular drug, are found in mycobacteria including Mycobacterium smegmatis and
      Mycobacterium tuberculosis. We have solved the structure of arylamine N
      acetyltransferase from M. smegmatis at a resolution of 1.7 A as a model for the
      highly homologous NAT from M. tuberculosis. The fold closely resembles that of
      NAT from Salmonella typhimurium, with a common catalytic triad and domain
      structure that is similar to certain cysteine proteases. The detailed geometry of
      the catalytic triad is typical of enzymes which use primary alcohols or thiols as
      activated nucleophiles. Thermal mobility and structural variations identify parts
      of NAT which might undergo conformational changes during catalysis. Sequence
      conservation among eubacterial NATs is restricted to structural residues of the
      protein core, as well as the active site and a hinge that connects the first two
      domains of the NAT structure. The structure of M. smegmatis NAT provides a
      template for modelling the structure of the M. tuberculosis enzyme and for
      structure-based ligand design as an approach to designing anti-TB drugs.

PMID- 12054805
TI  - NMR solution structure and dynamics of the peptidyl-prolyl cis-trans isomerase
      domain of the trigger factor from Mycoplasma genitalium compared to FK506-binding
      protein.
AB  - We have solved the solution structure of the peptidyl-prolyl cis-trans isomerase
      (PPIase) domain of the trigger factor from Mycoplasma genitalium by homo- and
      heteronuclear NMR spectroscopy. Our results lead to a well-defined structure with
      a backbone rmsd of 0.23 A. As predicted, the PPIase domain of the trigger factor
      adopts the FK506 binding protein (FKBP) fold. Furthermore, our NMR relaxation
      data indicate that the dynamic behavior of the trigger factor PPIase domain and
      of FKBP are similar. Structural variations when compared to FKBP exist in the
      flap region and within the bulges of strand 5 of the beta sheet. Although the
      active-site crevice is similar to that of FKBP, subtle steric variations in this
      region can explain why FK506 does not bind to the trigger factor. Sequence
      variability (27% identity) between trigger factor and FKBP results in significant
      differences in surface charge distribution and the absence of the first strand of
      the central beta sheet. Our data indicate, however, that this strand may be
      partially structured as "nascent" beta strand. This makes the trigger factor
      PPIase domain the most minimal representative of the FKBP like protein family of
      PPIases.

PMID- 12054804
TI  - Assembly of light-harvesting bacteriochlorophyll in a model transmembrane helix
      in its natural environment.
AB  - The transmembrane, bacteriochlorophyll-binding region of a bacterial light
      harvesting complex, (LH2-alpha from the photosynthetic bacterium Rhodobacter
      sphaeroides) was redesigned and overexpressed in a mutant of Rb. sphaeroides
      lacking LH2. Bacteriochlorophyll served as internal probe for the fitness of this
      new region for the assembly and energy transfer function of the LH2 complex. The
      ability to absorb and transfer light energy is practically undisturbed by the
      exchange of the transmembrane segment, valine -7 to threonine +6, of LH2-alpha
      with a 14 residue Ala-Leu sequence. This stretch makes up the residues of the
      transmembrane helix that are in close contact (< or =4.5 A) with the
      bacteriochlorophyll molecules that are coordinated through His of both the alpha
      and beta-subunits. In this Ala-Leu stretch, neither alpha-His0, which binds the
      bacteriochlorophyll, nor the adjacent alpha-Ile-1, were replaced. Novel LH2
      complexes composed of LH2-alpha with a model transmembrane sequence and a normal
      LH2-beta are assembled in vivo into a complex, the biochemical and spectroscopic
      properties of which closely resemble the native one. In contrast, the additional
      insertion of four residues just outside the C-terminal end of the model
      transmembrane helix leads to complete loss of functional antenna complex. The
      results suggest that light energy can be harvested and transferred efficiently by
      bacteriochlorophyll molecules attached to only few key residues distributed over
      the polypeptide, while residues at the bacteriochlorophyll-helix interface seem
      to be largely dispensable for the functional assembly of this membrane protein
      complex. This novel antenna with a simplified transmembrane domain and a built-in
      probe for assembly and function provides a powerful model system for
      investigation of the factors that contribute to the assembly of chromophores in
      membrane-embedded proteins.

PMID- 12054806
TI  - Crystal structure of the Homer 1 family conserved region reveals the interaction
      between the EVH1 domain and own proline-rich motif.
AB  - PSD-Zip45 (also named Homer 1c/Vesl-1L) is a synaptic scaffolding protein, which
      interacts with neurotransmitter receptors and other scaffolding proteins to
      target them into post-synaptic density (PSD), a specialized protein complex at
      the synaptic junction. Binding of the PSD-Zip45 to the receptors and scaffolding
      proteins results in colocalization and clustering of its binding partners in PSD.
      It has an Ena/VASP homology 1 (EVH1) domain in the N terminus for receptor
      binding, two leucine zipper motifs in the C terminus for clustering, and a
      linking region whose function is unclear despite the high level of conservation
      within the Homer 1 family. The X-ray crystallographic analysis of the largest
      fragment of residues 1-163, including an EVH1 domain reported here, demonstrates
      that the EVH1 domain contains an alpha-helix longer than that of the previous
      models, and that the linking part included in the conserved region of Homer 1
      (CRH1) of the PSD-Zip45 interacts with the EVH1 domain of the neighbour CRH1
      molecule in the crystal. The results suggest that the EVH1 domain recognizes the
      PPXXF motif found in the binding partners, and the SPLTP sequence (P-motif) in
      the linking region of the CRH1. The two types of binding are partly overlapped in
      the EVH1 domain, implying a mechanism to regulate multimerization of Homer 1
      family proteins.

PMID- 12054807
TI  - Crystal structure of E. coli Hsp100 ClpB nucleotide-binding domain 1 (NBD1) and
      mechanistic studies on ClpB ATPase activity.
AB  - E. coli Hsp100 ClpB was recently identified as a critical part in a multi
      chaperone system to play important roles in protein folding, protein transport
      and degradation in cell physiology. ClpB contains two nucleotide-binding domains
      (NBD1 and NBD2) within their primary sequences. NBD1 and NBD2 of ClpB can be
      classified as members of the large ATPase family known as ATPases associated with
      various cellular activities (AAA). To investigate how ClpB performs its ATPase
      activities for its chaperone activity, we have determined the crystal structure
      of ClpB nucleotide-binding domain 1 (NBD1) by MAD method to 1.80 A resolution.
      The NBD1 monomer structure contains one domain that comprises 11 alpha-helices
      and six beta-strands. When compared with the typical AAA structures, the crystal
      structure of ClpB NBD1 reveals a novel AAA topology with six-stranded beta-sheet
      as its core. The N-terminal portion of NBD1 structure has an extra beta-strand
      flanked by two extra alpha-helices that are not present in other AAA structures.
      Moreover, the NBD1 structure does not have a C-terminal helical domain as other
      AAA proteins do. No nucleotide molecule is bound with ClpB NBD1 in the crystal
      structure probably due to lack of the C-terminal helix domain in the structure.
      Isothermal titration calorimetry (ITC) studies of ClpB NBD1 and other ClpB
      deletion mutations showed that either ClpB NBD1 or NBD2 alone does not bind to
      nucleotides. However, ClpB NBD2 combined with ClpB C-terminal fragment can
      interact with one ADP or ATP molecule. ITC data also indicated that full-length
      ClpB could bind two ADP molecules or one ATP analogue ATPgammaS molecule. Further
      ATPase activity studies of ClpB and ClpB deletion mutants showed that only wild
      type ClpB have ATPase activity. None of ClpB NBD1 domain, NBD2 domain and NBD2
      with C-terminal fragment has detectable ATPase activities. On the basis of our
      structural and mutagenesis data, we proposed a "see-saw" model to illustrate the
      mechanisms by which ClpB performs its ATPase activities for chaperone functions.

PMID- 12054808
TI  - Three-dimensional structure of human tubulin chaperone cofactor A.
AB  - alpha and beta-Tubulin fold in a series of chaperone-assisted steps. At least
      five protein cofactors are involved in the post-chaperonin tubulin folding
      pathway and required to maintain the supply of tubulin; some of them also
      participate in microtubule dynamics. The first tubulin chaperone identified in
      the tubulin folding pathway was cofactor A (CoA). Here we describe the three
      dimensional structure of human CoA at 1.7 A resolution, determined by
      multiwavelength anomalous diffraction (MAD). The structure is a monomer with a
      rod-like shape and consists of a three-alpha-helix bundle, or coiled coil, with
      the second helix kinked by a proline break, offering a convex surface at one face
      of the protein. The helices are connected by short turns, one of them, between
      alpha2 and alpha3, including a 3(10)-helix. Peptide mapping analysis and
      competition experiments with peptides show that CoA interacts with beta-tubulin
      via the three alpha-helical regions but not with the rod-end loops. The main
      interaction occurs with the middle kinked alpha2 helix, at the convex face of the
      rod. Strong 3D structural homology is found with the Hsp70 chaperone cofactor BAG
      domain, suggesting that these proteins define a family of cofactors of simple
      compact architecture. Further structural homology is found with alpha
      spectrin/alpha-actinin repeats, all are rods of identical length of ten helical
      turns. We propose to call these three-helix bundles alpha ten modules.

PMID- 12054809
TI  - Interaction of the chaperone BiP with an antibody domain: implications for the
      chaperone cycle.
AB  - BiP is an Hsp70 homologue found in the endoplasmic reticulum of eukaryotic cells.
      Like other Hsp70 chaperones, BiP interacts with its substrate proteins in an ATP
      dependent manner. The functional analysis has so far been performed mainly with
      short, synthetic peptides. Here, we present an experimental system that allows to
      study the partial reactions of the BiP chaperone cycle for a natural substrate
      protein domain in its soluble, stably unfolded conformation. This unfolded
      antibody domain forms a binary complex with BiP in the absence of ATP. The
      dissociation of the BiP dimer seems to be the rate-limiting step in this
      reaction. The BiP-C(H)3 complexes dissociate rapidly in the presence of ATP. The
      affinity for BiP-binding peptides and the non-native antibody domain was
      determined to be similar, suggesting that only the peptide binding site is
      involved in these interactions. Furthermore, these results imply that, also in
      the context of the antibody domain, an extended peptide sequence is recognized.
      However, the accessibility of the BiP-binding site in the non-native protein
      seems to influence the kinetics of complex formation.

PMID- 12054810
TI  - Resolution of a disordered region at the entrance of the human sex hormone
      binding globulin steroid-binding site.
AB  - The crystal structure of human sex hormone-binding globulin (SHBG) has revealed
      how 5alpha-dihydrotestosterone intercalates between the two seven-stranded beta
      sheets of its amino-terminal laminin G-like domain. However, a region of disorder
      (residues 130 to 135 of SHBG) was identified together with a zinc-binding site in
      immediate proximity to the steroid. It has been important to resolve the
      structure of this region because previous studies have suggested that these
      residues may contribute to steroid binding directly. Here, we present the 2.35 A
      and 1.7 A crystal structures of the amino-terminal LG domain of SHBG obtained
      from a tetragonal crystal form and by EDTA-soaking of a trigonal crystal form,
      respectively. In both of these new structures, residues Pro130 to Arg135 are now
      clearly visible. Substitution of the two residues (Leu131Gly and Lys134Ala)
      pointing towards the steroid has shown that only Leu131 contributes significantly
      to steroid binding. Rather than covering the steroid-binding pocket in an
      extended conformation, a 3(10) helical turn is formed by residues Leu131 to
      Lys134 in this segment. Unfolding of this secondary structure element can either
      facilitate the entry of the steroids into the binding site or modulate the
      important contribution that Leu131 makes to steroid binding. A comparison with
      previous structures supports the concept that zinc binding re-orients the side
      chain of His136, and this residue serves as a lever causing disorder within the
      loop structure between Pro130 and Arg135.

PMID- 12054811
TI  - Inheritance and organisation of the mitochondrial genome differ between two
      Saccharomyces yeasts.
AB  - Petite-positive Saccharomyces yeasts can be roughly divided into the sensu
      stricto, including Saccharomyces cerevisiae, and sensu lato group, including
      Saccharomyces castellii; the latter was recently studied for transmission and the
      organisation of its mitochondrial genome. S. castellii mitochondrial molecules
      (mtDNA) carrying point mutations, which confer antibiotic resistance, behaved in
      genetic crosses as the corresponding point mutants of S. cerevisiae. While S.
      castellii generated spontaneous petite mutants in a similar way as S. cerevisiae,
      the petites exhibited a different inheritance pattern. In crosses with the wild
      type strains a majority of S. castellii petites was neutral, and the
      suppressivity in suppressive petites was never over 50%. The two yeasts also
      differ in organisation of their mtDNA molecules. The 25,753 bp sequence of S.
      castellii mtDNA was determined and the coding potential of both yeasts is
      similar. However, the S. castellii intergenic sequences are much shorter and do
      not contain sequences homologous to the S. cerevisiae biologically active
      intergenic sequences, as ori/rep/tra, which are responsible for the hyper
      suppressive petite phenotype found in S. cerevisiae. The structure of one
      suppressive S. castellii mutant, CA38, was also determined. Apparently, a short
      direct intergenic repeat was involved in the generation of this petite mtDNA
      molecule.

PMID- 12054812
TI  - Towards structural genomics of RNA: rapid NMR resonance assignment and
      simultaneous RNA tertiary structure determination using residual dipolar
      couplings.
AB  - We report a new residual dipolar couplings (RDCs) based NMR procedure for rapidly
      determining RNA tertiary structure demonstrated on a uniformly (15)N/(13)C
      labeled 27 nt variant of the trans-activation response element (TAR) RNA from HIV
      I. In this procedure, the time-consuming nuclear Overhauser enhancement (NOE)
      based sequential assignment step is replaced by a fully automated RDC-based
      assignment strategy. This approach involves examination of all allowed sequence
      specific resonance assignment permutations for best-fit agreement between
      measured RDCs and coordinates for sub-structures in a target RNA. Using idealized
      A-form geometries to model Watson-Crick helices and coordinates from a previous X
      ray structure to model a hairpin loop in TAR, the best-fit RDC assignment
      solutions are determined very rapidly (<five minutes of computational time) and
      are in complete agreement with corresponding NOE-based assignments. Orientational
      constraints derived from RDCs are used simultaneously to assemble sub-structures
      into an RNA tertiary conformation. Through enhanced speeds of application and
      reduced reliance on chemical shift dispersion, this RDC-based approach lays the
      foundation for rapidly determining RNA conformations in a structural genomics
      context, and may increase the size limit of RNAs that can be examined by NMR.

PMID- 12054813
TI  - FIS modulates the kinetics of successive interactions of RNA polymerase with the
      core and upstream regions of the tyrT promoter.
AB  - We have applied laser UV photo-footprinting to characterise kinetically complexes
      involving the activator protein FIS, RNA polymerase and the tyrT promoter of
      Escherichia coli. FIS photo-footprints strongly to three binding sites upstream
      of the core promoter. The polymerase photo-footprints in the near-consensus -35
      hexamer on the non-template strand of DNA in a fashion similar to that of stable
      complexes involving the lacUV5 promoter. The kinetics of the interactions of
      polymerase alone with the tyrT promoter differ from those observed previously at
      the lacUV5 promoter. In the absence of FIS, we observe an upstream polymerase
      induced signal at -122 within FIS site III that occurs subsequent to changes in
      the core promoter region and is strongly dependent on negative supercoiling.
      These observations support the proposal that the upstream region of the promoter
      is wrapped around the polymerase. We propose that the wrapped DNA allows the
      polymerase to overcome, at least in part, the barrier to DNA untwisting imparted
      by the G+C-rich discriminator. We further suggest that FIS plays a similar role
      and may facilitate polymerase escape.

PMID- 12054814
TI  - Crystal structure of archaeosine tRNA-guanine transglycosylase.
AB  - Archaeosine tRNA-guanine transglycosylase (ArcTGT) catalyzes the exchange of
      guanine at position 15 in the D-loop of archaeal tRNAs with a free 7-cyano-7
      deazaguanine (preQ(0)) base, as the first step in the biosynthesis of an archaea
      specific modified base, archaeosine (7-formamidino-7-deazaguanosine). We
      determined the crystal structures of ArcTGT from Pyrococcus horikoshii at 2.2 A
      resolution and its complexes with guanine and preQ(0), at 2.3 and 2.5 A
      resolutions, respectively. The N-terminal catalytic domain folds into an
      (alpha/beta)(8) barrel with a characteristic zinc-binding site, showing
      structural similarity with that of the bacterial queuosine TGT (QueTGT), which is
      involved in queuosine (7-[[(4,5-cis-dihydroxy-2-cyclopenten-1-yl)-amino]methyl]-7
      deazaguanosine) biosynthesis and targets the tRNA anticodon. ArcTGT forms a
      dimer, involving the zinc-binding site and the ArcTGT-specific C-terminal domain.
      The C-terminal domains have novel folds, including an OB fold-like "PUA domain",
      whose sequence is widely conserved in eukaryotic and archaeal RNA modification
      enzymes. Therefore, the C-terminal domains may be involved in tRNA recognition.
      In the free-form structure of ArcTGT, an alpha-helix located at the rim of the
      (alpha/beta)(8) barrel structure is completely disordered, while it is ordered in
      the guanine-bound and preQ(0)-bound forms. Structural comparison of the
      ArcTGT.preQ(0), ArcTGT.guanine, and QueTGT.preQ(1) complexes provides novel
      insights into the substrate recognition mechanisms of ArcTGT.

PMID- 12054815
TI  - NMR studies of the backbone flexibility and structure of human growth hormone: a
      comparison of high and low pH conformations.
AB  - (15)N NMR relaxation parameters and amide (1)H/(2)H-exchange rates have been used
      to characterize the structural flexibility of human growth hormone (rhGH) at
      neutral and acidic pH. Our results show that the rigidity of the molecule is
      strongly affected by the solution conditions. At pH 7.0 the backbone dynamics
      parameters of rhGH are uniform along the polypeptide chain and their values are
      similar to those of other folded proteins. In contrast, at pH 2.7 the overall
      backbone flexibility increases substantially compared to neutral pH and the
      average order parameter approaches the lower limit expected for a folded protein.
      However, a significant variation of the backbone dynamics through the molecule
      indicates that under acidic conditions the mobility of the residues becomes more
      dependent on their location within the secondary structure units. In particular,
      the order parameters of certain loop regions decrease dramatically and become
      comparable to those found in unfolded proteins. Furthermore, the HN-exchange
      rates at low pH reveal that the residues most protected from exchange are
      clustered at one end of the helical bundle, forming a stable nucleus. We suggest
      that this nucleus maintains the overall fold of the protein under destabilizing
      conditions. We therefore conclude that the acid state of rhGH consists of a
      structurally conserved, but dynamically more flexible helical core surrounded by
      an aura of highly mobile, unstructured loops. However, in spite of its prominent
      flexibility the acid state of rhGH cannot be considered a "molten globule" state
      because of its high stability. It appears from our work that under certain
      conditions, a protein can tolerate a considerable increase in flexibility of its
      backbone, along with an increased penetration of water into its core, while still
      maintaining a stable folded conformation.

PMID- 12054816
TI  - Design of peptide-based inhibitors of human islet amyloid polypeptide
      fibrillogenesis.
AB  - Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits
      found in the pancreas of over 90% of all cases of type-2 diabetes. We have
      generated a series of overlapping hexapeptides to target an amyloidogenic region
      of IAPP (residues 20-29) and examined their effects on fibril assembly. Peptide
      fragments corresponding to SNNFGA (residues 20-25) and GAILSST (residues 24-29)
      were strong inhibitors of the beta-sheet transition and amyloid aggregation.
      Circular dichroism indicated that even at 1:1 molar ratios, these peptides
      maintained full-length IAPP (1-37) in a largely random coil conformation.
      Negative stain electron microscopy revealed that co-incubation of these peptides
      with IAPP resulted in the formation of only semi-fibrous aggregates and loss of
      the typical high density and morphology of IAPP fibrils. This inhibitory
      activity, particularly for the SNNFGA sequence, also correlated with a reduction
      in IAPP-induced cytotoxicity as determined by cell culture studies. In contrast,
      the peptide NFGAIL (residues 22-27) enhanced IAPP fibril formation. Conversion to
      the amyloidogenic beta-sheet was immediate and the accompanying fibrils were more
      dense and complex than IAPP alone. The remaining peptide fragments either had no
      detectable effects or were only weakly inhibitory. Specificity of peptide
      activity was illustrated by the fragments, SSNNFG and AILSST. These differed from
      the most active inhibitors by only a single amino acid residue but delayed the
      random-to-beta conformational change only when used at higher molar ratios. This
      study has identified internal IAPP peptide fragments which can regulate
      fibrillogenesis and may be of therapeutic use for the treatment of type-2
      diabetes.

PMID- 12054817
TI  - Structural basis for thermophilic protein stability: structures of thermophilic
      and mesophilic malate dehydrogenases.
AB  - The three-dimensional structure of four malate dehydrogenases (MDH) from
      thermophilic and mesophilic phototropic bacteria have been determined by X-ray
      crystallography and the corresponding structures compared. In contrast to the
      dimeric quaternary structure of most MDHs, these MDHs are tetramers and are
      structurally related to tetrameric malate dehydrogenases from Archaea and to
      lactate dehydrogenases. The tetramers are dimers of dimers, where the structures
      of each subunit and the dimers are similar to the dimeric malate dehydrogenases.
      The difference in optimal growth temperature of the corresponding organisms is
      relatively small, ranging from 32 to 55 degrees C. Nevertheless, on the basis of
      the four crystal structures, a number of factors that are likely to contribute to
      the relative thermostability in the present series have been identified. It
      appears from the results obtained, that the difference in thermostability between
      MDH from the mesophilic Chlorobium vibrioforme on one hand and from the moderate
      thermophile Chlorobium tepidum on the other hand is mainly due to the presence of
      polar residues that form additional hydrogen bonds within each subunit.
      Furthermore, for the even more thermostable Chloroflexus aurantiacus MDH, the use
      of charged residues to form additional ionic interactions across the dimer-dimer
      interface is favored. This enzyme has a favorable intercalation of His-Trp as
      well as additional aromatic contacts at the monomer-monomer interface in each
      dimer. A structural alignment of tetrameric and dimeric prokaryotic MDHs reveal
      that structural elements that differ among dimeric and tetrameric MDHs are
      located in a few loop regions.

PMID- 12054818
TI  - Structures of glycopeptide antibiotics with peptides that model bacterial cell
      wall precursors.
AB  - The vancomycin-related antibiotics balhimycin and degluco-balhimycin have been
      crystallized in complexes with di-, tri- and pentapeptides that emulate bacterial
      cell-wall precursors, and four structures determined at atomic resolution (<1 A).
      In addition to the features expected from previous structural and spectroscopic
      studies, two new motifs were observed that may prove important in the design of
      antibiotics modified to overcome bacterial resistance. A changed binding mode was
      found in two dipeptide complexes, and a new type of face-to-face oligomerization
      (in addition to the well-established back-to-back dimerization) was seen when the
      model peptide reaches a critical fraction of the size of the cell-wall precursor
      pentapeptide. The extensive interactions involving both antibiotic and peptide
      molecules in this interface should appreciably enhance the kinetic and
      thermodynamic stability of the complexes. In the pentapeptide complex, the
      relative positions of the peptides are close to those required for d-Ala
      elimination, so this structure may provide a realistic model for the prevention
      of the enzyme-catalyzed cell-wall crosslinking by antibiotic binding.

PMID- 12054819
TI  - The mechanism and pathway of pH induced swelling in cowpea chlorotic mottle
      virus.
AB  - Normal mode analysis based on a simplified energy function was used to study the
      swelling process of the icosahedral virus, cowpea chlorotic mottle virus (CCMV).
      Native state virus particles (coat proteins) of this T=3 icosahedral virus have
      been shown to undergo a large conformational change to a swollen state when metal
      ions are removed or the pH is raised. A normal mode analysis based on the native
      state capsid showed one preferential direction, a breathing mode, that explains
      the majority of the structural rearrangement necessary to bring the native
      structure close to the swollen state. From the native form of CCMV, the structure
      can be displaced along the direction of a single breathing mode by different
      amounts to create several candidate swollen structures and a putative pathway for
      virus expansion. The R-factor between these predicted swollen capsid structures
      and experimental electron density from cryoelectron microscopy (cryo-EM)
      measurements is then calculated to indicate how well each structure satisfies the
      experimental measurements on the swollen capsid state. A decrease of the
      crystallographic R-factor value from approximately 72% to approximately 49% was
      observed for these simple incremental displacements along the breathing mode. The
      simultaneous displacement of the native structure along other relevant
      (symmetric, non-degenerate) modes produce a structure with an R-factor of 45%,
      which is further reduced to 43.9% after minimization: a value in good accord with
      models based on the EM data at 28 A resolution. Based on the incrementally
      expanded structures, a pathway for the swelling process has been proposed.
      Analysis of the intermediate structures along this pathway indicates a
      significant loss of interactions at the quasi-3-fold interfaces occurs in the
      initial stages of the swelling process and this serves as a trigger for the
      compact to swollen transition. Furthermore, the pH dependent swelling appears to
      be triggered by the titration of a single residue with an anomalous pK(a) value
      in the unswollen particle.

PMID- 12054820
TI  - HIV-1 nucleocapsid protein as a nucleic acid chaperone: spectroscopic study of
      its helix-destabilizing properties, structural binding specificity, and annealing
      activity.
AB  - Assembly of infectious retroviral particles involves recognition of specific
      sequences on the viral RNA by the nucleocapsid (NC) domain of the Gag
      polyprotein, and subsequent stoichiometric binding of the processed NC protein
      along the entire length of the RNA. NC proteins also act as nucleic acid
      chaperones. They accelerate nucleic acid hybridization and strand exchange, which
      may be critical during the initial stages of reverse transcription. In order to
      better understand these properties, we have studied the nucleic acid helix
      destabilizing t(m)-depressing) and binding activities of HIV-1 NCp7 protein with
      a variety of substrates, and the real-time kinetics of NC-induced strand
      exchange. At low ionic strength (0.01 M Na phosphate, pH 7.0) and saturating
      levels of protein, NCp7 displays moderate helix-destabilizing activity on double
      stranded DNA. Saturating levels of NCp7 lowered the t(m) of a synthetic 28 base
      pair 28(+)/28(-) oligonucleotide duplex by about 10 deg. C (51 to 41 degrees C).
      The presence of single-stranded calf thymus DNA (equimolar with duplex)
      eliminated the t(m) depression, whereas double-stranded calf thymus DNA only
      altered the t(m) of the 28-mer duplex by about 2 deg. C. Similar effects were
      seen with duplexes with single-stranded overhangs or internal single-stranded
      gaps. Binding experiments utilizing intrinsic tryptophan quenching indicated
      significant affinity (K(d) about 0.1 microM) for both single-stranded and double
      stranded forms of the 28-mer in 0.01 M sodium phosphate at 25 degrees C, although
      long-chain (calf thymus double-stranded) DNA displayed a much lower affinity. The
      effects of NCp7 on the kinetics of nucleic acid annealing, strand exchange, and
      strand displacement were determined by use of oligonucleotides with end-labeled
      fluorophores serving as donor-acceptor pairs. NCp7 accelerated all these
      reactions. In the strand exchange reaction, an imperfect duplex, 28(+)/21(-), was
      reacted with a perfect complement, 28(-). The kinetics of 28(+)/28(-) annealing
      in this reaction did not conform to a simple bimolecular model, but could be well
      fit to the sum of two exponential decays. Addition of stoichiometric levels of
      NCp7 increased the rate constants of both components, and significantly increased
      the fraction of exchange associated with the rapid process. Increasing levels of
      28(-) also increased the rapid fraction, as well as the rapid rate constant. This
      concentration dependence indicates that, although the kinetic decays appear
      biexponential, at least one of the steps is bimolecular. Simple annealing
      reactions, 28(+) with 28(-), could be fit to single-exponential decays, and their
      magnitudes in the presence of NCp7 were comparable to the rapid step of annealing
      observed for exchange reactions, suggesting that this step is connected with
      annealing. Strand dissociation during exchange was monitored by placing the
      fluorescent acceptor on the 21(-) strand. The results, though complex, suggest
      that the slow step of exchange is largely associated with the dissociation of the
      shorter oligonucleotide. Analogous experiments were performed with variants of
      these oligonucleotides, and the results are in line with the 28(+)/21(-)/28(-)
      experiments. On the basis of an analysis of the effect of increasing levels of
      28(-) on the formation of the perfect 28 bp duplex from the imperfect duplex, we
      propose that NCp7 forms a ternary complex intermediate with imperfect duplex and
      28(-), and suggest several ways by which such an intermediate would facilitate
      strand exchange.

PMID- 12054821
TI  - The structure of apo human glutamate dehydrogenase details subunit communication
      and allostery.
AB  - The structure of human glutamate dehydrogenase (GDH) has been determined in the
      absence of active site and regulatory ligands. Compared to the structures of
      bovine GDH that were complexed with coenzyme and substrate, the NAD binding
      domain is rotated away from the glutamate-binding domain. The electron density of
      this domain is more disordered the further it is from the pivot helix. Mass
      spectrometry results suggest that this is likely due to the apo form being more
      dynamic than the closed form. The antenna undergoes significant conformational
      changes as the catalytic cleft opens. The ascending helix in the antenna moves in
      a clockwise manner and the helix in the descending strand contracts in a manner
      akin to the relaxation of an extended spring. A number of spontaneous mutations
      in this antenna region cause the hyperinsulinism/hyperammonemia syndrome by
      decreasing GDH sensitivity to the inhibitor, GTP. Since these residues do not
      directly contact the bound GTP, the conformational changes in the antenna are
      apparently crucial to GTP inhibition. In the open conformation, the GTP binding
      site is distorted such that it can no longer bind GTP. In contrast, ADP binding
      benefits by the opening of the catalytic cleft since R463 on the pivot helix is
      pushed into contact distance with the beta-phosphate of ADP. These results
      support the previous proposal that purines regulate GDH activity by altering the
      dynamics of the NAD binding domain. Finally, a possible structural mechanism for
      negative cooperativity is presented.

PMID- 12054822
TI  - Crystal structure of HslUV complexed with a vinyl sulfone inhibitor:
      corroboration of a proposed mechanism of allosteric activation of HslV by HslU.
AB  - On the basis of the structure of a HslUV complex, a mechanism of allosteric
      activation of the HslV protease, wherein binding of the HslU chaperone propagates
      a conformational change to the active site cleft of the protease, has been
      proposed. Here, the 3.1 A X-ray crystallographic structure of Haemophilus
      influenzae HslUV complexed with a vinyl sulfone inhibitor is described. The
      inhibitor, which reacts to form a covalent linkage to Thr1 of HslV, binds in an
      "antiparallel beta" manner, with hydrogen-bond interactions between the peptide
      backbone of the protease and that of the inhibitor, and with two leucinyl side
      chains of the inhibitor binding in the S1 and S3 specificity pockets of the
      protease. Comparison of the structure of the HslUV-inhibitor complex with that of
      HslV without inhibitor and in the absence of HslU reveals that backbone
      interactions would correctly position a substrate for cleavage in the HslUV
      complex, but not in the HslV protease alone, corroborating the proposed mechanism
      of allosteric activation. This activation mechanism differs from that of the
      eukaryotic proteasome, for which binding of activators opens a gated channel that
      controls access of substrates to the protease, but does not perturb the active
      site environment.

PMID- 12054824
TI  - Transient intermediary states with high and low folding probabilities in the
      apparent two-state folding equilibrium of ACBP at low pH.
AB  - Measurements of the stability as a function of pH for the acyl-coenzyme A binding
      protein (ACBP) has shown a significant difference in the pH transition midpoint
      measured by NMR spectroscopy at pH 3.12 and the transition midpoint measured at
      pH 2.92 and 2.97 by circular dichroism and by fluorescence spectroscopy,
      respectively. A similar behavior has not been observed in other proteins. It is
      suggested that these differences arise because the population of the unfolded
      molecules still contains significant amounts of native like secondary and
      tertiary structure. NMR spectroscopy measures the concentration of the two
      components of the folding unfolding equilibrium individually, whereas circular
      dichroism and fluorescence measure the concentration of the conformations of the
      light-absorbing chromophores present in both the folded and the unfolded
      molecules. In the narrow pH range, nascent structure can be detected as the
      average amount of secondary structure per unfolded molecule and hydrophobic
      interactions in the population of unfolded molecules. These structures are not
      observable immediately by NMR spectroscopy; however, a chemical shift analysis of
      the peptide backbone (13)C chemical shift indicates strongly the existence of
      short-lived and transient helical structures at pH 2.3. Magnetization transfer
      studies have been applied to study the equilibrium between folded and unfolded
      ACBP near the pH transition point measured by NMR. This study has shown that
      there are two categories of subpopulations in the population of unfolded ACBP.
      One for which magnetization can be transferred to the folded form during the
      folding process, and one for which transfer is not observed. The molecules of the
      latter population of unfolded protein apparently, do not fold within the time
      frame of the magnetization transfer experiment. This result suggests the
      existence of a subpopulation of the acid-unfolded protein molecules with a high
      propensity for folding. It is suggested that in this subpopulation, a particular
      set of native like interactions in the peptide backbone and between side-chains
      in the peptide chain have to be formed.

PMID- 12054823
TI  - Structural dynamics of the membrane translocation domain of colicin E9 and its
      interaction with TolB.
AB  - In order for the 61 kDa colicin E9 protein toxin to enter the cytoplasm of
      susceptible cells and kill them by hydrolysing their DNA, the colicin must
      interact with the outer membrane BtuB receptor and Tol translocation pathway of
      target cells. The translocation function is located in the N-terminal domain of
      the colicin molecule. (1)H, (1)H-(1)H-(15)N and (1)H-(13)C-(15)N NMR studies of
      intact colicin E9, its DNase domain, minimal receptor-binding domain and two N
      terminal constructs containing the translocation domain showed that the region of
      the translocation domain that governs the interaction of colicin E9 with TolB is
      largely unstructured and highly flexible. Of the expected 80 backbone NH
      resonances of the first 83 residues of intact colicin E9, 61 were identified,
      with 43 of them being assigned specifically. The absence of secondary structure
      for these was shown through chemical shift analyses and the lack of long-range
      NOEs in (1)H-(1)H-(15)N NOESY spectra (tau(m)=200 ms). The enhanced flexibility
      of the region of the translocation domain containing the TolB box compared to the
      overall tumbling rate of the protein was identified from the relatively large
      values of backbone and tryptophan indole (15)N spin-spin relaxation times, and
      from the negative (1)H-(15)N NOEs of the backbone NH resonances. Variable
      flexibility of the N-terminal region was revealed by the (15)N T(1)/T(2) ratios,
      which showed that the C-terminal end of the TolB box and the region immediately
      following it was motionally constrained compared to other parts of the N
      terminus. This, together with the observation of inter-residue NOEs involving
      Ile54, indicated that there was some structural ordering, resulting most probably
      from the interactions of side-chains. Conformational heterogeneity of parts of
      the translocation domain was evident from a multiplicity of signals for some of
      the residues. Im9 binding to colicin E9 had no effect on the chemical shifts or
      other NMR characteristics of the region of colicin E9 containing the TolB
      recognition sequence, though the interaction of TolB with intact colicin E9 bound
      to Im9 did affect resonances from this region. The flexibility of the
      translocation domain of colicin E9 may be connected with its need to recognise
      protein partners that assist it in crossing the outer membrane and in the
      translocation event itself.

PMID- 12054825
TI  - The interaction of the molecular chaperone alpha-crystallin with unfolding alpha
      lactalbumin: a structural and kinetic spectroscopic study.
AB  - The unfolding of the apo and holo forms of bovine alpha-lactalbumin (alpha-LA)
      upon reduction by dithiothreitol (DTT) in the presence of the small heat-shock
      protein alpha-crystallin, a molecular chaperone, has been monitored by visible
      and UV absorption spectroscopy, mass spectrometry and (1)H NMR spectroscopy. From
      these data, a description and a time-course of the events that result from the
      unfolding of both forms of the protein, and the state of the protein that
      interacts with alpha-crystallin, have been obtained. alpha-LA contains four
      disulphide bonds and binds a calcium ion. In apo alpha-LA, the disulphide bonds
      are reduced completely over a period of approximately 1500 seconds. Fully reduced
      alpha-LA adopts a partly folded, molten globule conformation that aggregates and,
      ultimately, precipitates. In the presence of an equivalent mass of alpha
      crystallin, this precipitation can be prevented via complexation with the
      chaperone. alpha-Crystallin does not interfere with the kinetics of the reduction
      of disulphide bonds in apo alpha-LA but does stabilise the molten globule state.
      In holo alpha-LA, the disulphide bonds are less accessible to DTT, because of the
      stabilisation of the protein by the bound calcium ion, and reduction occurs much
      more slowly. A two-disulphide intermediate aggregates and precipitates rapidly.
      Its precipitation can be prevented only in the presence of a 12-fold mass excess
      of alpha-crystallin. It is concluded that kinetic factors are important in
      determining the efficiency of the chaperone action of alpha-crystallin. It
      interacts efficiently with slowly aggregating, highly disordered intermediate
      (molten globule) states of alpha-LA. Real-time NMR spectroscopy shows that the
      kinetics of the refolding of apo alpha-LA following dilution from denaturant are
      not affected by the presence of alpha-crystallin. Thus, alpha-crystallin is not a
      chaperone that is involved in protein folding per se. Rather, its role is to
      stabilise compromised, partly folded, molten globule states of proteins that are
      destined for precipitation.

PMID- 12054826
TI  - Intradomain disulfide bonds impede formation of the alternatively folded state of
      antibody chains.
AB  - Antibodies undergo significant conformational changes upon acidification, leading
      to the formation of an alternatively folded state. Here, we analyzed the
      conformation of MAK 33 Fab and its light chain at acidic pH, both in the reduced
      and oxidized form. At acidic pH, the proteins exhibited a highly structured, but
      non-native conformation, corresponding to the alternatively folded state,
      previously described for the intact antibody. However, the requirements to form
      this alternative structure were different for the oxidized and reduced protein.
      Whereas in the oxidized form of the immunoglobulin light chain the alternatively
      folded state could only be detected at pH<1.4, the reduced light chain already
      adopted this structure at pH 2. Thermal denaturation measurements revealed that,
      surprisingly, the alternatively folded state of the reduced light chain was more
      stable than that of the oxidized protein at pH 1.4. This indicates that the
      intradomain disulfide bonds, which stabilize the native state of antibody
      domains, impede the formation of the alternatively folded state.

PMID- 12054827
TI  - Water contributes actively to the rapid crossing of a protein unfolding barrier.
AB  - The cold-shock protein CspB folds rapidly in a N <= => U two-state reaction via a
      transition state that is about 90% native in its interactions with denaturants
      and water. This suggested that the energy barrier to unfolding is overcome by
      processes occurring in the protein itself, rather than in the solvent.
      Nevertheless, CspB unfolding depends on the solvent viscosity. We determined the
      activation volumes of unfolding and refolding by pressure-jump and high-pressure
      stopped-flow techniques in the presence of various denaturants. The results
      obtained by these methods agree well. The activation volume of unfolding is
      positive (Delta V(++)(NU)=16(+/-4) ml/mol) and virtually independent of the
      nature and the concentration of the denaturant. We suggest that in the transition
      state the protein is expanded and water molecules start to invade the hydrophobic
      core. They have, however, not yet established favorable interactions to
      compensate for the loss of intra-protein interactions. The activation volume of
      refolding is positive as well (Delta V(++)(NU)=53(+/-6) ml/mol) and, above 3 M
      urea, independent of the concentration of the denaturant. At low concentrations
      of urea or guanidinium thiocyanate, Delta V(++)(UN) decreases significantly,
      suggesting that compact unfolded forms become populated under these conditions.

PMID- 12054828
TI  - Assessment of proteasomal cleavage probabilities from kinetic analysis of time
      dependent product formation.
AB  - Proteasomes are multicatalytic cellular protease complexes that degrade
      intracellular proteins into smaller peptides. Proteasomal in vitro digests have
      revealed that the various peptide bonds of a given substrate are cleaved in a
      highly selective manner. Regarding the key role of proteasomes as the main
      supplier of antigenic peptides for MHC class I-mediated antigen presentation, it
      is important to know to what extent these preferences for specific peptide bonds
      may vary among proteasomes of different cellular origin and of different subunit
      composition. Here, we quantify such cleavage rates by means of a kinetic
      proteasome model that relates the time-dependent changes of the amount of any
      generated peptide to the rates with which this peptide can be either generated
      from longer precursor peptides or degraded into smaller successor peptides.
      Numerical values for these rates are estimated by minimizing the distance between
      simulated and measured time-courses. The proposed method is applied to kinetic
      data obtained by combining HPLC fractionation and mass spectrometry (MS) to trace
      the degradation of two model peptides (pp89-25mer and LLO-27mer) by either the
      constitutive (T2) or immunoproteasome (T2.27). To convert the intensity of the MS
      signals into the respective peptide amounts, we use two methods leading to
      similar results: experimental calibration curves and theoretically determined
      linear scaling functions based on a novel approach using mass conservation rules.
      Comparison of the cleavage probabilities and procession rates obtained for the
      two types of proteasomes reveals that the striking differences between the time
      dependent peptide profiles can be accounted for mainly by a generally higher
      turnover rate of the immunoproteasome. For the pp89-25mer, there is no
      significant change of the cleavage probabilities for any of the ten observed
      cleavage sites. For the LLO-27mer, there appears to be a significant change in
      the cleavage probabilities for four of the nine observed cleavage sites when
      switching from the constitutive to the immunoproteasome.

PMID- 12054829
TI  - Thermodynamics and folding kinetics analysis of the SH3 domain form discrete
      molecular dynamics.
AB  - We perform a detailed analysis of the thermodynamics and folding kinetics of the
      SH3 domain fold with discrete molecular dynamic simulations. We propose a protein
      model that reproduces some of the experimentally observed thermodynamic and
      folding kinetic properties of proteins. Specifically, we use our model to study
      the transition state ensemble of the SH3 fold family of proteins, a set of
      unstable conformations that fold to the protein native state with probability
      1/2. We analyze the participation of each secondary structure element formed at
      the transition state ensemble. We also identify the folding nucleus of the SH3
      fold and test extensively its importance for folding kinetics. We predict that a
      set of amino acid contacts between the RT-loop and the distal hairpin are the
      critical folding nucleus of the SH3 fold and propose a hypothesis that explains
      this result.

PMID- 12054830
TI  - Core side-chain packing and backbone conformation in Lpp-56 coiled-coil mutants.
AB  - Native proteins exhibit precise geometric packing of atoms in their hydrophobic
      interiors. Nonetheless, controversy remains about the role of core side-chain
      packing in specifying and stabilizing the folded structures of proteins. Here we
      investigate the role of core packing in determining the conformation and
      stability of the Lpp-56 trimerization domain. The X-ray crystal structures of Lpp
      56 mutants with alanine substitutions at two and four interior core positions
      reveal trimeric coiled coils in which the twist of individual helices and the
      helix-helix spacing vary significantly to achieve the most favored superhelical
      packing arrangement. Introduction of each alanine "layer" into the hydrophobic
      core destabilizes the superhelix by 1.4 kcal mol(-1). Although the methyl groups
      of the alanine residues pack at their optimum van der Waals contacts in the
      coiled-coil trimer, they provide a smaller component of hydrophobic interactions
      than bulky hydrophobic side-chains to the thermodynamic stability. Thus, specific
      side-chain packing in the hydrophobic core of coiled coils are important
      determinants of protein main-chain conformation and stability.

PMID- 12054831
TI  - Interactions between bacterial flagellar axial proteins in their monomeric state
      in solution.
AB  - The axial structure of the bacterial flagellum is composed of many different
      proteins, such as hook protein and flagellin, and each protein forms a short or
      long axial segment one after another in a well-defined order along the axis.
      Under physiological conditions, most of these proteins are stable in the
      monomeric state in solution, and spontaneous polymerization appears to be
      suppressed, as demonstrated clearly for flagellin, probably to avoid undesirable
      self-assembly in the cytoplasmic space. However, no systematic studies of the
      possible associations between monomeric axial proteins in solution have been
      carried out. We therefore studied self and cross-association between hook
      protein, flagellin and three hook-associated proteins, HAP1, HAP2 and HAP3, in
      all possible pairs, by gel-filtration and analytical centrifugation, and found
      interactions in the following two cases only. Flagellin facilitated HAP3
      aggregation into beta-amyloid-like filaments, but without stable binding between
      the two. Addition of HAP3 to HAP2 resulted in disassembly of preformed HAP2
      decamers and formation of stable HAP2-HAP3 heterodimers. HAP2 missing either of
      its disordered terminal regions did not form the heterodimer, whereas HAP3
      missing either of its disordered terminal regions showed stable heterodimer
      formation. This polarity in the heterodimer interactions suggests that the
      interactions between HAP2 and HAP3 in solution are basically the same as those in
      the flagellar axial structure. We discuss these results in relation to the
      assembly mechanism of the flagellum.

PMID- 12054833
TI  - Homology, pathway distance and chromosomal localization of the small molecule
      metabolism enzymes in Escherichia coli.
AB  - Here, we analyse Escherichia coli enzymes involved in small molecule metabolism
      (SMM). We introduce the concept of pathway distance as a measure of the number of
      distinct metabolic steps separating two SMM enzymes, and we consider protein
      homology (as determined by assigning enzymes to structural and sequence families)
      and gene interval (the number of genes separating two genes on the E. coli
      chromosome). The relationships between these three contexts (pathway distance,
      homology and chromosomal localisation) is investigated extensively. We make use
      of these relationships to suggest possible SMM evolution mechanisms. Homology
      between enzyme pairs close in the SMM was higher than expected by chance but was
      still rare. When observed, homologues usually conserved their reaction mechanism
      and/or co-factor binding rather than shared substrate binding. The correlation
      between pathway distance and gene intervals was clear. Enzymes catalysing nearby
      SMM reactions were usually encoded by genes close by on the E. coli chromosome.
      We found many co-regulated blocks of three to four genes (usually non-homologous)
      encoding enzymes occurring within four metabolic steps of one another; nearly all
      of these blocks formed part of known or predicted operons. The "inline reuse" of
      enzymes (i.e. the use of the same enzyme to catalyse two or more different steps
      of a metabolic pathway) is also discussed: of these enzymes, four were
      multifunctional (i.e. catalysed a different reaction in each instance), nine had
      multiple substrate specificity (i.e. catalysed the same reaction on different
      substrates in each instance) and one catalysed the same reaction on the same
      substrate but as part of two different complexes. We also identified 59 sets of
      isozymic proteins most commonly duplicated to function under different
      conditions, or with a different preferred substrate or minor substrate. In
      addition to transcriptional units, isozymes and inline reuse of enzymes provide
      mechanisms for controlling the SMM network. Our data suggest that several pathway
      evolution mechanisms may occur in concert, although chemistry-driven
      duplication/recruitment is favoured. SMM exploits regulatory strategies involving
      chromosomal location, isozymes and the reuse of enzymes.

PMID- 12054832
TI  - Improving coiled-coil stability by optimizing ionic interactions.
AB  - Alpha-helical coiled coils are a common protein oligomerization motif stabilized
      mainly by hydrophobic interactions occurring along the coiled-coil interface. We
      have recently designed and solved the structure of a two-heptad repeat coiled
      coil peptide that is stabilized further by a complex network of inter- and
      intrahelical salt-bridges in addition to the hydrophobic interactions. Here, we
      extend and improve the de novo design of this two heptad-repeat peptide by four
      newly designed peptides characterized by different types of ionic interactions.
      The contribution of these different types of ionic interactions to coiled-coil
      stability are analyzed by CD spectroscopy and analytical ultracentrifugation. We
      show that all peptides are highly alpha-helical and two of them are 100% dimeric
      under physiological conditions. Furthermore, we have solved the X-ray structure
      of the most stable of these peptides and the rational design principles are
      verified by comparing this structure to the structure of the parent peptide. We
      show that by combining the most favorable inter- and intrahelical salt-bridge
      arrangements it is possible to design coiled-coil oligomerization domains with
      improved stability properties.

PMID- 12054835
TI  - Two notions of conspicuity and the classification of phyllotaxis.
AB  - Invoking cylindrical Bravais lattices, Adler (1974, 1977) proposed a
      mathematically precise definition for the botanical classification of
      phyllotaxis. It is based on opposed pairs of parastichy families, that are
      conspicuous and visible. Jean (1988) generalized this concept to non-opposed
      pairs of parastichy families. In the present paper it is shown that this
      generalization implies a notion of conspicuity different from Adler's. This is
      made obvious by redefining the key terms of the two approaches. Both
      classifications are well defined. For Adler's, this is shown by presenting a
      general proof for his conjecture that conspicuous (in the sense of Adler) opposed
      pairs of parastichy families are visible. There are indications that in
      applications to models of phyllotaxis (van Iterson model, inhibitor models) their
      solutions are better characterized by Jean's classification. The differences
      between Adler's and Jean's classification show up only in very rare cases, so
      that the practice of pattern determination is only insignificantly touched by the
      present results. It turns out that the widely used contact parastichy method to
      determine phyllotactic patterns gives results according to Jean's classification
      rather than Adler's.

PMID- 12054836
TI  - A model for glucose-induced wave propagation in pancreatic islets of Langerhans.
AB  - A reaction-diffusion type model is constructed, describing the spatio-temporal
      dynamics of the basic intracellular variables assumed to be involved in the
      initiation of the insulin secretion process by beta -cells in the pancreatic
      islets of Langerhans. The model includes equations for the electric membrane
      potential of the cells, with respective kinetics for ionic currents, for
      concentrations of both free and stored intracellular calcium, and for the intra-
      and extracellular concentrations of glucose. An empirical expression connecting
      the equation for the intracellular glucose concentration to the electrical
      equation is introduced. The model reproduces the events observed in experiments
      in vitro upon external glucose application to the islets of Langerhans, such as
      usual bursting oscillations of the membrane potential and corresponding
      oscillations of the intracellular calcium concentration. It also allows
      simulation of electric wave propagation through the islet, initiated by the
      spatial gradient of glucose concentration within the islet. The gradient emerges
      due to glucose diffusing into the islets from the external medium, being high at
      the edges. The latter results show that glucose diffusion presents a means for
      wave initiation in the islets, which supports our previous assumption (Aslanidi
      et al., 2001).

PMID- 12054837
TI  - Group beneficial norms can spread rapidly in a structured population.
AB  - Group beneficial norms are common in human societies. The persistence of such
      norms is consistent with evolutionary game theory, but existing models do not
      provide a plausible explanation for why they are common. We show that when a
      model of imitation used to derive replicator dynamics in isolated populations is
      generalized to allow for population structure, group beneficial norms can spread
      rapidly under plausible conditions. We also show that this mechanism allows
      recombination of different group beneficial norms arising in different
      populations.

PMID- 12054838
TI  - A mathematical model of chemoreception for odours and taste.
AB  - We propose a mathematical model based on the occupation theory and on the
      hypothesis that, for a given stimulus, there exist two kinds of receptors. The
      receptors of the first kind react by a two-step process, first forming an
      intermediate inactive compound which is then changed into an active depolarizing
      form (this scheme was already used by Del Castillo & Katz, 1957). In the same
      way, the receptors of the second kind react by a two-step process, first forming
      an intermediate inactive compound which is then changed into an active
      hyperpolarizing form. The response is assumed to be proportional to the
      difference between the fraction of the active depolarizing compound and that of
      the active hyperpolarizing compound. The present paper deals only with the time
      course of the intensity of the response: in the first part, when a continuous
      flow of stimulus is applied and in the second part, when this continuous flow is
      removed. It does not deal with the quality and the discrimination of odours. The
      proposed mathematical model accounts for the depolarizing responses (which are
      the most frequent ones), the hyperpolarizing responses, the mixed responses
      reported by Patte et al. (1989), the off-responses reported by Takagi & Shibuya
      (1959) and for their variability, and the latent period in the olfactory response
      (Ottoson, 1974).

PMID- 12054839
TI  - Bi-trophic mathematical model for pest adaptation to a resistant crop.
AB  - A version of the Lotka-Volterra predator-prey model with logistic crop growth is
      modified to explore the rate of adaptation of a herbivore to a pest-resistant
      crop. This provides a phenotypic model for the evolution of resistance in a
      population comprising three different pest types each defined by differing
      parameter values for respiration rate and crop palatability. Expressions
      estimating the rates of increase of the fitter pest types are obtained as a
      function of the food qualities, and respiration and mortality rates. Potential
      strategies for delaying the rate of adaptation with regard to the expressions
      derived above, via the use of pest-susceptible refugia and natural enemies, are
      discussed. Although the model is formulated as one in which a single gene is the
      factor conferring resistance it can be interpreted and used independently of
      this.

PMID- 12054840
TI  - Begging for milk: evolution of teat massaging in suckling pigs.
AB  - We present a model that simulates the evolution of teat massaging (begging) by
      suckling piglets (Sus scrofa) and milk distribution among teats (provisioning) by
      their mothers. Contrary to previous begging models, this one incorporates an
      ontogenetic dimension in that the inherited begging and provisioning rules are
      repeatedly allowed to interact, and their consequences for milk intake, growth
      and death probability are assessed, during each nursing. We test the model under
      three selection regimes differing in the relative importance of the between
      litter selection component. We show that the selection regime with the strongest
      between-litter selection component leads to lowest begging levels and most
      effective milk utilization, thus supporting the hypothesis that selection based
      on whole litters may attenuate sibling competition.

PMID- 12054841
TI  - Toxin-producing plankton may act as a biological control for planktonic blooms-
      field study and mathematical modelling.
AB  - Termination of planktonic blooms is of great importance to human health,
      ecosystem, environment, tourism and fisheries. Toxic substances released by
      plankton play an important role in this context. The effect of toxin-producing
      plankton (TPP) on zooplankton is observed from the field-collected samples and
      mathematical modelling. Information from both the studies led us to suggest that
      TPP may terminate the planktonic blooms by decreasing the grazing pressure of
      zooplankton and thus acts as a biological control.

PMID- 12054842
TI  - Pattern formation of the cone mosaic in the zebrafish retina: a cell
      rearrangement model.
AB  - In fish retinas, cone photoreceptor cells are arranged in two-dimensional regular
      patterns, called cone mosaics. In the zebrafish retina, four subtypes of cone
      cells, which are maximally sensitive to different wavelengths of light, appear in
      quasi-periodic patterns. The pattern formation mechanism is unknown. Here, I
      develop a mathematical model to examine whether cell adhesion can explain the
      formation of the zebrafish mosaic. I assume that the movement of differentiated
      cells is responsible for generating the pattern, and that the movement rate is
      modified by cell adhesion. The pattern is formed if the magnitudes of cell
      adhesion between cell types are chosen appropriately. I determine the conditions
      of cell adhesion for generating the pattern. I also compare this cell
      rearrangement model with a previously studied model in which the pattern is
      formed by transitions of cell fate. The condition for obtaining the focal pattern
      is looser in the cell rearrangement model than in the fate transition model.

PMID- 12054844
TI  - Construction of an associative memory using unstable periodic orbits of a chaotic
      attractor.
AB  - Unstable periodic orbits are the skeleton of a chaotic attractor. We constructed
      an associative memory based on the chaotic attractor of an artificial neural
      network, which associates input patterns to unstable periodic orbits. By
      processing an input, the system is driven out of the ground state to one of the
      pre-defined disjunctive areas of the attractor. Each of these areas is associated
      with a different unstable periodic orbit. We call an input pattern learned if the
      control mechanism keeps the system on the unstable periodic orbit during the
      response. Otherwise, the system relaxes back to the ground state on a chaotic
      trajectory. The major benefits of this memory device are its high capacity and
      low-energy consumption. In addition, new information can be simply added by
      linking a new input to a new unstable periodic orbit.

PMID- 12054843
TI  - Emergent polyethism as a consequence of increased colony size in insect
      societies.
AB  - A threshold reinforcement model in insect societies is explored over a range of
      colony sizes and levels of task demand to examine their effects upon worker
      polyethism. We find that increasing colony size while keeping the demand
      proportional to the colony size causes an increase in the differentiation among
      individuals in their activity levels, thus explaining the occurrence of elitism
      (individuals that do a disproportionately large proportion of work) in insect
      societies. Similar results were obtained when the overall work demand is
      increased while keeping the colony size constant. Our model can reproduce a whole
      suite of distributions of the activity levels among colony members that have been
      found in empirical studies. When there are two tasks, we demonstrate that
      increasing demand and colony size generates highly specialized individuals, but
      without invoking any strict assumptions about spatial organization of work or any
      inherent abilities of individuals to tackle different tasks. Importantly, such
      specialization only occurs above a critical colony size such that smaller
      colonies contain a set of undifferentiated equally inactive individuals while
      larger colonies contain both active specialists and inactive generalists, as has
      been found in empirical studies and is predicted from other theoretical
      considerations.

PMID- 12054845
TI  - What is the unique function of SAPK3/p38gamma in cardiac myocytes?

PMID- 12054846
TI  - A thousand times NO.

PMID- 12054847
TI  - Diastolic dysfunction and the aging heart.

PMID- 12054848
TI  - Divergent signaling pathways converge on GATA4 to regulate cardiac hypertrophic
      gene expression.

PMID- 12054849
TI  - Potential roles of plasminogen activator system in coronary vascular remodeling
      induced by long-term nitric oxide synthase inhibition.
AB  - Recent studies have indicated that a number of factors contribute to the
      pathophysiology in response to nitric oxide synthase (NOS) inhibition. We
      previously demonstrated that plasminogen activator inhibitor-1 deficient (PAI-1-/
      ) mice are protected against hypertension and perivascular fibrosis induced by
      relatively short-term NOS inhibition. In this study, we compared the temporal
      changes in systolic blood pressure and coronary perivascular fibrosis induced by
      long-term treatment with N(omega)-nitro- L -arginine methyl ester (L -NAME) in
      wild type (WT), PAI-1(-/-) and tissue-type plasminogen activator deficient (t-PA
      /-) mice. After initiating L -NAME, systolic blood pressure increased in all
      groups at 2 weeks. Over a 16 week study period, systolic blood pressure increased
      to 143+/-3 mmHg (mean+/-SEM) in WT animals, 139+/-2 in t-PA-/- mice vs 129+/-2 in
      PAI-1-/- mice (P < 0.01). Coronary perivascular fibrosis increased in L -NAME
      treated WT and t-PA(-/-) mice compared to each control group (P<0.01 in WT,
      P<0.05 in t-PA-/-), while PAI-1-/- mice were protected against fibrosis induced
      by L -NAME. t-PA deficiency did not accentuate the vascular pathology or the
      changes in blood pressure. In situ zymography demonstrated augmented
      gelatinolytic activity in PAI-1-/- mice at baseline, suggesting that PAI-1
      deficiency prevents the increase of collagen deposition by promoting matrix
      degradation. Plasma TGF-beta1 levels increased in L -NAME-treated WT and PAI-1-/-
      mice (P < 0.01), but not in L -NAME-treated t-PA-/- mice. These findings support
      the hypothesis that the plasminogen activator system protects against the
      structural vascular changes induced by long-term NOS inhibition. While PAI-1
      deficiency protects against L -NAME-induced hypertension and perivascular
      fibrosis, t-PA deficiency does not exacerbate the vascular pathology or
      hypertension.

PMID- 12054850
TI  - Characterisation of murine cytomegalovirus myocarditis: cellular infiltration of
      the heart and virus persistence.
AB  - Myocarditis triggered by a viral infection has integral viral and immunological
      aspects associated with the pathogenesis of disease. The present study was
      performed to analyse the cellular inflammatory response in the heart and
      cytomegalovirus replication during the development of myocarditis in vivo. We
      examined murine cytomegalovirus in an animal model of myocarditis using both
      susceptible BALB/c and resistant C57BL/6 mice. The heart infiltrating cells of
      BALB/c mice were found to comprise predominantly CD8+ T cells, with other cells
      of the CD4+ T cell, macrophage, B cell and neutrophil phenotype. Infectious MCMV
      titres in the heart were low and replicative virus could not be isolated beyond
      the first week post-infection (p.i.). Direct viral lysis of myocytes in vitro and
      apoptosis of cardiac cells in vivo was observed. Furthermore, viral DNA was
      detected in the heart of both mouse strains throughout the development of chronic
      disease. Viral gB RNA was detected during the first 35 days p.i. However, viral
      transcript for ie1 RNA but not gB RNA was found in the heart during the late
      stage of disease, suggesting latent viral infection of the heart. Our findings
      suggest that maintenance of the chronic phase of myocarditis involving post-viral
      immunological responses can occur in the presence of little infectious virus
      replication in the heart.

PMID- 12054851
TI  - Action potential prolongation in cardiac myocytes of old rats is an adaptation to
      sustain youthful intracellular Ca2+ regulation.
AB  - Advanced age in rats is accompanied by reduced expression of the sarcoplasmic
      reticulum (SR) Ca2+ pump (SERCA-2). The amplitudes of intracellular Ca2+
      (Ca2+(i)) transients and contractions in ventricular myocytes isolated from old
      (23-24-months) rats (OR), however, are similar to those of young (4-6-months) rat
      myocytes (YR). OR myocytes also manifest slowed inactivation of L-type Ca2+
      current (I(CaL)) and marked prolongation of action potential (AP) duration. To
      determine whether and how age-associated AP prolongation preserves the Ca2+(i)
      transient amplitude in OR myocytes, we employed an AP-clamp technique with
      simultaneous measurements of I(CaL) (with Na+ current, K+ currents and Ca2+
      influx via sarcolemmal Na+-Ca2+ exchanger blocked) and Ca2+(i) transients in OR
      rat ventricular myocytes dialyzed with the fluorescent Ca2+ probe, indo-1.
      Myocytes were stimulated with AP-shaped voltage clamp waveforms approximating the
      configuration of prolonged, i.e. the native, AP of OR cells (AP-L), or with short
      AP waveforms (AP-S), typical of YR myocytes. Changes in SR Ca2+ load were
      assessed by rapid, complete SR Ca2+ depletions with caffeine. As expected, during
      stimulation with AP-S vs AP-L, peak I(CaL) increased, by 21+/-4%, while the
      I(CaL) integral decreased, by 19+/-3% (P<0.01 for each). Compared to AP-L,
      stimulation of OR myocytes with AP-S reduced the amplitudes of the Ca2+(i)
      transient by 31+/-6%, its maximal rate of rise (+dCa2+(i)/dt(max); a sensitive
      index of SR Ca2+ release flux) by 37+/-4%, and decreased the SR Ca2+ load by 29+/
      4% (P<0.01 for each). Intriguingly, AP-S also reduced the maximal rate of the
      Ca2+(i) transient relaxation and prolonged its time to 50% decline, by 35+/-5%
      and 33+/-7%, respectively (P<0.01 for each). During stimulation with AP-S, the
      gain of Ca2+-induced Ca2+ release (CICR), indexed by +dCa2+(i)/dt(max)/I(CaL),
      was reduced by 46+/-4% vs AP-L (P<0.01). We conclude that the effects of an
      application of a shorter AP to OR myocytes to reduce +dCa2+(i)/dt(max) and the
      Ca2+ transient amplitude are attributable to a reduction in SR Ca2+ load,
      presumably due to a reduced I(CaL) integral and likely also to an increased Ca2+
      extrusion via sarcolemmal Na+-Ca2+ exchanger. The decrease in the Ca2+(i)
      transient relaxation rate in OR cells stimulated with shorter APs may reflect a
      reduction of Ca2+/calmodulin-kinase II-regulated modulation of Ca2+ uptake via
      SERCA-2, consequent to a reduced local Ca2+ release in the vicinity of SERCA-2,
      also attributable to reduced SR Ca2+ load. Thus, the reduction of CICR gain
      during stimulation with AP-S is the net result of both a diminished SR Ca2+
      release and an increased peak I(CaL). These results suggest that ventricular
      myocytes of old rats utilize AP prolongation to preserve an optimal SR Ca2+
      loading, CICR gain and relaxation of Ca2+(i) transients.

PMID- 12054852
TI  - Transcriptional activation of the BNP gene by lipopolysaccharide is mediated
      through GATA elements in neonatal rat cardiac myocytes.
AB  - Lipopolysaccharide (LPS) has a profound effect on cardiac performance through a
      collapse of the vasculature. In this study, we determined whether LPS has a
      direct effect on the cardiac myocytes by examining the expression of the BNP gene
      in cultured neonatal rat cardiac myocytes. Northern blot analysis showed that LPS
      induces the expression of the BNP gene. Time-course experiments revealed that BNP
      mRNA levels were increased 1 h after LPS stimulation. Enhanced induction of BNP
      was observed 3 h after stimulation when expression of CD14, a specific receptor
      for LPS, was markedly induced. LPS-mediated BNP expression was completely
      inhibited by the pretreatment of SB203580, a specific inhibitor for p38 MAPK as
      well as by genistein, a broad range tyrosine kinase inhibitor. In accordance with
      these results, LPS increases phosphorylation of p38 mitogen-activated protein
      kinase (MAPK). Transient transfection assays revealed that low dose (1 ng/ml) of
      LPS induces the luciferase activity derived from the construct containing the BNP
      promoter spanning from -1000 and +80 in front of the luciferase gene.
      Cotransfection of the expression vectors for constitutive active forms of Rac1,
      MKK3 and p38 MAPK significantly increased BNP promoter activity. Mutation of the
      GATA sequence located at -95 and -84 abolished such an induction of BNP promoter
      activity. Overexpression of CD14 enhanced the LPS's effect on BNP promoter. These
      results indicate that LPS induces the BNP gene expression through a pathway
      involving CD14, Rac1, p38 MAPK and GATA elements. In addition to the induction of
      BNP expression by hemodynamic overload, our data suggest that elevated levels of
      BNP under the endotoxemic condition is partly mediated through the increased
      expression of CD14, which lies upstream of the Rac1-p38 MAPK pathway.

PMID- 12054853
TI  - PI3 kinase and not p42/p44 appears to be implicated in the protection conferred
      by ischemic preconditioning.
AB  - Ischemic preconditioning results in an immediate phase of protection against
      lethal ischemia/reperfusion injury that is comprised of both irreversible
      necrosis and programmed cell death, apoptosis. We hypothesized that
      preconditioning may activate putative anti-apoptotic pathways, through the
      induction of either phosphatidyl inositol 3-OH kinase (PI3 kinase) or p42/p44
      extracellular receptor kinase, attenuating total cell death. Isolated perfused
      rat hearts were preconditioned with two cycles of 5 min ischemia and 10 min
      reperfusion. Then they were frozen for Western blot analysis or subjected to 35
      min regional ischemia and 120 min reperfusion prior to infarct size assessment.
      Selective PI3 kinase inhibitors, wortmannin (W, 100 n M) and LY294002 (LY, 15
      microM) and the p42/p44 inhibitor, PD 98059 (PD, 10 and 50 microM), were
      individually infused during the preconditioning protocol. One further group of
      hearts received both inhibitors (W and PD). The results were expressed as
      percentage of infarction within the risk zone. Inhibition of PI3 kinase by either
      W or LY partially abrogated the infarct sparing effect of ischemic
      preconditioning (I/R%: 44.6+/-2.7 in C, 17.6+/-2.0 in IP, vs 32.2+/-4.2 in W, and
      30.9+/-2.6 in LY, P<0.05). Inhibition of ERK phosphorylation however, had no
      significant effect upon infarct size reduction (17.6+/-2.0 in ischemic
      preconditioning vs 21.4+/-3.0 in IP+10 microM PD and 15.2+/-1.4 in IP+50 microM
      PD, P>0.05). Western blot analysis confirmed that PD abrogated the
      phosphorylation of p42/p44 and LY the phosphorylation of AKT. Combined inhibition
      with PD+W failed to further attenuate protection (27.6+/-1.3%, P>0.1). These data
      appear to demonstrate that the PI3 kinase, but not the p42/p44 cascade, is
      implicated in early ischemic preconditioning.

PMID- 12054854
TI  - Inhibition of betaARK1 restores impaired biochemical beta-adrenergic receptor
      responsiveness but does not rescue CREB(A133) induced cardiomyopathy.
AB  - The myocardial beta-adrenergic receptor (betaAR) system plays a key role in
      dysfunctional signaling and physiology of the failing heart. Recently we
      described a murine model of dilated cardiomyopathy (DCM) produced by cardiac
      specific expression of a dominant negative form of the CREB transcription factor
      (CREB(A133) mice). CREB(A133) mice display abnormalities within the betaAR
      signaling system including loss of inotropic reserve. Rapid desensitization of
      betaARs is mediated by the betaAR kinase (betaARK1), which is upregulated during
      heart failure. Inhibition of betaARK1 activity in the heart via expression of a
      peptide inhibitor (betaARKct) has been shown to enhance myocardial function and
      to "rescue" several animal models of heart failure. To determine the role of
      betaAR dysfunction in the progression of DCM in the CREB(A133) mice, we interbred
      them with mice expressing the betaARKct. Concurrent expression of the betaARKct
      peptide and CREB(A133) in mouse hearts resulted in the normalization of elevated
      betaARK1 levels. This biochemical change resulted in partial restoration of
      isoproterenol-stimulated adenylate cyclase activity as well as improvement in
      fractional shortening in response to betaAR stimulation. Interestingly, the
      progression of DCM and premature mortality was not altered. Therefore, the
      pathogenesis of DCM in CREB(A133) mice does not appear to involve abnormal betaAR
      signaling as a key element in its pathological progression and accordingly, the
      restoration of betaAR signaling is not sufficient to prevent the development and
      progression of all forms of heart failure.

PMID- 12054855
TI  - Epiandrosterone, a metabolite of testosterone precursor, blocks L-type calcium
      channels of ventricular myocytes and inhibits myocardial contractility.
AB  - The dehydroepiandrosterone metabolite epiandrosterone (EPI) inhibits the pentose
      phosphate pathway (PPP) and dilates isolated blood vessels pre-contracted by
      partial depolarization. We found that EPI (10-100 microM) also dose-dependently
      decreases left-ventricular developed pressure (LVDP), the rate of myocardial
      contraction (+d p /d t), and the pressure rate product (PRP); at 100 microM EPI,
      LVDP (131+/-9 vs 34+/-7 mmHg), +d p /dt (1515+/-94 vs 542+/-185 mmHg/s), and PRP
      (37870+/-2471 vs 9498+/-2375 HR x mmHg/min) were all significantly (P<0.05)
      reduced. EPI also elevated CPP in isolated hearts, decreased levels of myocardial
      NADPH and nitrite, and dose-dependently relaxed rat aortic rings pre-contracted
      with KCl. Electrophysiological analysis of single ventricular myocytes using
      whole cell clamp showed EPI to dose-dependently (100 n M-100 microM) and
      reversibly inhibit L-type channel currents carried by Ba2+ (IBa) (IC50=42+/-6
      microM) by as much as 50%. At 30 microM, EPI shifted the steady-state
      inactivation curve to more negative potentials (V50=-26.6 mV vs -38.0 mV),
      thereby accelerating the decay of IBa during depolarization. These results
      suggest that EPI may act as a L-type Ca2+ channel antagonist with properties
      similar to those of 1,4-dihydropyridine (DHP) Ca2+ channel blockers.

PMID- 12054856
TI  - The hexameric ring structure of the Escherichia coli RuvB branch migration
      protein.
AB  - The RuvB protein is part of the homologous recombination machinery in prokaryotic
      cells. Many studies have shown that RuvB is organized into hexameric rings
      functioning as DNA pumps at Holliday junctions, using ATP hydrolysis to drive
      branch migration. Structures now exist for two RuvB proteins, as well as for
      several structurally homologous proteins, including the replication factor-C
      small subunit (RFCS). Two models for the possible hexameric organization of RuvB
      subunits have been proposed, based upon the hexameric structures of NSF and HslU,
      two AAA-ATPases involved in vesicle fusion and proteolysis, respectively. We have
      used electron microscopy to generate an improved three-dimensional reconstruction
      of the double hexamers formed by Escherichia coli RuvB on double-stranded DNA. We
      find that an atomic model of the hexameric RFCS provides a significantly better
      fit to the RuvB hexamer than do the models for RuvB generated from NSF and HslU.
      This suggests that there may be a highly conserved structure for many proteins
      involved in different aspects of DNA replication, recombination, transcription
      and repair.

PMID- 12054857
TI  - Human genome search in celiac disease: mutated gliadin T-cell-like epitope in two
      human proteins promotes T-cell activation.
AB  - Discovery of a number of novel and known human genes whose protein products bear
      striking similarity to two or more wheat gliadin domains raised the possibility
      that human intestinal non-HLA peptides homologous to celiac T-cell epitopes could
      play a role in non-HLA gene specification in celiac disease. Database searching
      of the entire human genome identified only 11 gut-expressed proteins with high T
      cell epitope homology, particularly to the DQ2-gamma-I-gliadin epitope (i.e.
      TFIIA, FOXJ2 and IgD; mean BestFit quality score=40 versus random value of 24).
      Others were similar to DQ2-alpha-I-gliadin (i.e. PAX9; BestFit quality 46 versus
      20 for random), or DQ2-alpha-II-gliadin (PHLDA1, known in mice as the T-cell
      death-associated gene; BestFit quality 43 versus 30 for random) epitopes. Among
      proteins previously screened for gliadin homology, noteworthy was achaete scute
      homologous protein (DQ2-alpha-I-gliadin; BestFit quality 41 versus 22 for
      random). With the exception of IgD, all are nuclear factors. Paying particular
      attention to the position of potential major histocompatibility complex (MHC)
      anchor residues, several were selected for testing in a DQ2-gamma-I-gliadin
      restricted T-cell system. All native 10-mer peptides were inactive, even when
      deamidated, but V96F substitution of deamidated TFIIA amino acid residues 91-100
      stimulated IL-2 release at levels exceeding the wheat gliadin positive control.
      Also active, but only slightly, was L1009F substitution of AIB3 amino acid
      residues 1004-1013. PlotSimilarity alignment of TFIIAs from eight species
      revealed subthreshold similarity score in the peptide region, in contrast to the
      highly conserved amino and carboxy termini. Molecular modeling of TFIIA[V96F]
      peptide points to an important juxtaposition of an upwardly projecting
      phenylalanine residue at peptide position 6 that likely contacts a receptor
      complementarity-determining region, and a downwardly projecting glutamic acid
      residue that fits into the shallow MHC P7 pocket. These observations tentatively
      point to a new multi-gene hypothesis for the initiation of celiac disease in
      which deamidated free human peptides with T-cell epitope homology (particularly
      those made more homologous by mutation) escape negative selection, as per
      deamidation of the HEL(48-62) peptide in the hen egg lysozyme model of
      autoimmunity. Deamidation following peptide release due to injury triggers
      inflammation, thereafter repeatedly provoked by dietary gliadin immunodominant
      peptides concentrated in the proximal small intestine.

PMID- 12054858
TI  - Delineating the site of interaction on the pIII protein of filamentous
      bacteriophage fd with the F-pilus of Escherichia coli.
AB  - The minor coat protein pIII at one end of the filamentous bacteriophage fd,
      mediates the infection of Escherichia coli cells displaying an F-pilus. pIII has
      three domains (D1, D2 and D3), terminating with a short hydrophobic segment at
      the C-terminal end. Domain D2 binds to the tip of F-pilus, which is followed by
      retraction of the pilus and penetration of the E. coli cell membrane, the latter
      involving an interaction between domain D1 and the TolA protein in the membrane.
      Surface residues on the D2 domain of pIII were replaced systematically with
      alanine. Mutant virions were screened for D2-pilus interaction in vivo by
      measuring the release of infectious virions from E. coli F(+) cells infected with
      the mutants. A competitive ELISA was developed to measure in vitro the ability of
      mutant phages to bind to purified pili. This allowed the identification of amino
      acid residues involved in binding to F and to EDP208 pili. These residues were
      found to cluster on the outer rim of the 3D structure of the D2 domain,
      unexpectedly identifying this as the F-pilus binding region on the pIII protein.

PMID- 12054859
TI  - Biophysical studies of eIF4E cap-binding protein: recognition of mRNA 5' cap
      structure and synthetic fragments of eIF4G and 4E-BP1 proteins.
AB  - mRNA 5'-cap recognition by the eukaryotic translation initiation factor eIF4E has
      been exhaustively characterized with the aid of a novel fluorometric, time
      synchronized titration method, and X-ray crystallography. The association
      constant values of recombinant eIF4E for 20 different cap analogues cover six
      orders of magnitude; with the highest affinity observed for m(7)GTP
      (approximately 1.1 x 10(8) M(-1)). The affinity of the cap analogues for eIF4E
      correlates with their ability to inhibit in vitro translation. The association
      constants yield contributions of non-covalent interactions involving single
      structural elements of the cap to the free energy of binding, giving a reliable
      starting point to rational drug design. The free energy of 7-methylguanine
      stacking and hydrogen bonding (-4.9 kcal/mol) is separate from the energies of
      phosphate chain interactions (-3.0, -1.9, -0.9 kcal/mol for alpha, beta, gamma
      phosphates, respectively), supporting two-step mechanism of the binding. The
      negatively charged phosphate groups of the cap act as a molecular anchor,
      enabling further formation of the intermolecular contacts within the cap-binding
      slot. Stabilization of the stacked Trp102/m(7)G/Trp56 configuration is a
      precondition to form three hydrogen bonds with Glu103 and Trp102.
      Electrostatically steered eIF4E-cap association is accompanied by additional
      hydration of the complex by approximately 65 water molecules, and by ionic
      equilibria shift. Temperature dependence reveals the enthalpy-driven and entropy
      opposed character of the m(7)GTP-eIF4E binding, which results from dominant
      charge-related interactions (DeltaH degrees =-17.8 kcal/mol, DeltaS degrees= 
      23.6 cal/mol K). For recruitment of synthetic eIF4GI, eIF4GII, and 4E-BP1
      peptides to eIF4E, all the association constants were approximately 10(7) M(-1),
      in decreasing order: eIF4GI>4E-BP1>eIF4GII approximately 4E-BP1(P-Ser65)
      approximately 4E-BP1(P-Ser65/Thr70). Phosphorylation of 4E-BP1 at Ser65 and Thr70
      is insufficient to prevent binding to eIF4E. Enhancement of the eIF4E affinity
      for cap occurs after binding to eIF4G peptides.

PMID- 12054860
TI  - Alternate usage of two dimerization initiation sites in HIV-2 viral RNA in vitro.
AB  - An essential step in the replication cycle of all retroviruses is the
      dimerization of genomic RNA prior to or during encapsidation and budding. In HIV
      1, a stem-loop structure in the genomic RNA called the dimerization initiation
      site, or DIS, has been well characterized. However, the identification of the
      structure(s) necessary for dimerization of HIV-2 genomic RNA has been less
      straightforward, as reflected by recent conflicting reports. Here, using a
      variety of mutant and wild-type RNA constructs and a systematic analysis of
      experimental conditions, we demonstrate that two dimerization sites in HIV-2 RNA
      are clearly discernible under different experimental conditions. A short sequence
      overlapping the primer binding site acts as the default dimerization site for
      wild-type viral RNA transcripts of several lengths provided that dimerization
      incubation conditions do not include a high heat step (>50 degrees C), and
      electrophoresis is carried out under mild conditions that do not deplete the RNA
      of magnesium. However, some RNA constructs are able to dimerize through stem-loop
      1 (SL1), which is the structure homologous to the HIV-1 DIS, under certain
      experimental conditions. Interestingly, deletion or mutation of the default PBS
      dimerization site leads to efficient usage of the SL1 dimerization site. This
      study defines conditions under which each site may be used for dimerization and
      demonstrates, furthermore, the facility with which the two sites can substitute
      for each other. This is suggestive of a switching mechanism that may be used in
      the viral replication cycle.

PMID- 12054861
TI  - Kinetic studies and structural models of the association of E. coli sigma(70) RNA
      polymerase with the lambdaP(R) promoter: large scale conformational changes in
      forming the kinetically significant intermediates.
AB  - The kinetics of interaction of Esigma(70) RNA polymerase (R) with the lambdaP(R)
      promoter (P) were investigated by filter binding over a broad range of
      temperatures (7.3-42 degrees C) and concentrations of RNA polymerase (1-123 nM)
      in large excess over promoter DNA. Under all conditions examined, the kinetics of
      formation of competitor-resistant complexes (I(2), RP(o)) are single-exponential
      with first order rate constant beta(CR). Interpretation of the polymerase
      concentration dependence of beta(CR) in terms of the three step mechanism of open
      complex formation yields the equilibrium constant K(1) for formation of the first
      kinetically significant intermediate (I(1)) and the forward rate constant (k(2))
      for the conformational change converting I(1) to the second kinetically
      significant intermediate I(2): R + P-->(K(1))<--I(1)(k(2))-->I(2). Use of rapid
      quench mixing allows K(1) and k(2) to be individually determined over the entire
      temperature range investigated, previously not possible at this promoter using
      manual mixing. Given the large (>60 bp) interface formed in I(1), its relatively
      small binding constant K(1) at 37 degrees C at this [salt] (approximately 6 x
      10(6) M(-1)) strongly argues that binding free energy is used to drive large
      scale structural changes in polymerase and/or promoter DNA or other coupled
      processes. Evidence for coupling of protein folding is provided by the large and
      negative activation heat capacity of k(a)[DeltaC(o,++)(a)= -1.5(+/-0.2)kcal K(
      1)], now shown to originate directly from formation of I(1) [DeltaC(o)(1)= 
      1.4(+/-0.3)kcal K(-1)] rather than from the formation of I(2) as previously
      proposed. The isomerization I(1)-->I(2) exhibits relatively slow kinetics and has
      a very large temperature-independent Arrhenius activation energy [E(act)(2)=
      34(+/-2)kcal]. This kinetic signature suggests that formation of the transition
      state (I(1)-I(2)++ involves large conformational changes dominated by changes in
      the exposure of polar and/or charged surface to water. Structural and biochemical
      data lead to the following hypotheses to interpret these results. We propose that
      formation of I(1) involves coupled folding of unstructured regions of polymerase
      (beta, beta' and sigma(70)) and bending of promoter DNA (in the -10 region). We
      propose that interactions with region 2 of sigma(70) and possibly domain 1 of
      beta induce a kink at the -11/-12 base pairs of the lambdaP(R) promoter which
      places the downstream DNA (-5 to +20) in the jaws of the beta and beta' subunits
      of polymerase in I(1). These early interactions of beta and beta' with the DNA
      downstream of position -5 trigger jaw closing (with coupled folding) and
      subsequent steps of DNA opening.

PMID- 12054862
TI  - Directed evolution of restriction endonuclease BstYI to achieve increased
      substrate specificity.
AB  - Restriction endonucleases have proven to be especially resistant to engineering
      altered substrate specificity, in part, due to the requirement of a cognate DNA
      methyltransferase for cellular DNA protection. The thermophilic restriction
      endonuclease BstYI recognizes and cleaves all hexanucleotide sequences described
      by 5'-R GATCY-3' (where R=A or G and Y=C or T). The recognition of a degenerate
      sequence is a relatively common feature of the more than 3000 characterized
      restriction endonucleases. However, very little is known concerning substrate
      recognition by such an enzyme. Our objective was to investigate the substrate
      specificity of BstYI by attempting to increase the specificity to recognition of
      only AGATCT. By a novel genetic selection/screening process, two BstYI variants
      were isolated with a preference for AGATCT cleavage. A fundamental element of the
      selection process is modification of the Escherichia coli host genomic DNA by the
      BglII N4-cytosine methyltransferase to protect AGATCT sites. The amino acid
      substitutions resulting in a partial change of specificity were identified and
      combined into one superior variant designated NN1. BstYI variant NN1 displays a
      12-fold preference for cleavage of AGATCT over AGATCC or GGATCT. Moreover,
      cleavage of the GGATCC sequence is no longer detected. This study provides
      further evidence that laboratory evolution strategies offer a powerful
      alternative to structure-guided protein design.

PMID- 12054863
TI  - Elucidation of primary (alpha(3)N) and vestigial (alpha(5)) heavy metal-binding
      sites in Staphylococcus aureus pI258 CadC: evolutionary implications for metal
      ion selectivity of ArsR/SmtB metal sensor proteins.
AB  - Despite a common evolutionary origin, individual members of the ArsR/SmtB family
      of bacterial metal-responsive transcriptional repressors sense a wide range of
      heavy-metal ions. The molecular basis for this metal ion selectivity is unclear.
      Here, we establish that Staphylococcus aureus plasmid pI258 CadC, a
      Cd(II)/Pb(II)/Bi(III)/Zn(II) sensor, contains two distinct metal-binding sites: a
      thiolate-rich alpha(3)N site comprised exclusively of cysteine ligands that
      preferentially binds larger, softer metal ions such as Cd(II), Pb(II) and
      Bi(III); and a second C-terminal alpha(5) site, found at the dimer interface,
      that is devoid of cysteine ligands and preferentially binds smaller, harder metal
      ions [Co(II) and Zn(II)] concurrently with metal binding to the alpha(3)N site.
      Optical absorption and X-ray spectroscopies reveal that the alpha(3)N site can
      adopt distinct coordination geometries in order to accommodate different metal
      ions, i.e. Cd(II), Bi(III), Co(II) and Zn(II) form distorted tetrahedral S(4)
      complexes, while Pb(II) adopts a trigonal S(3) complex. Characterization of
      mutant CadCs reveals that the alpha(3)N site is composed of Cys58 and Cys60 from
      the alpha(3) helix of the helix-turn-helix DNA-binding domain and Cys7 and/or
      Cys11 from the N-terminal "arm" of CadC; Cys11 is excluded from the Pb(II)
      coordination sphere. Only the thiolate-rich alpha(3)N site is metalloregulatory
      for repressor binding to a fluorescein-labeled cad O/P oligonucleotide upon
      coordination to Cd(II), Pb(II), Bi(III), Zn(II), and weakly for Co(II).
      Substitution of Cys60 and Cys7 with non-ligating residues specifically abrogates
      metal-dependent negative regulation of cad O/P binding, despite the fact that
      C60G and C7G CadCs maintain high affinity for metals in altered coordination
      complexes. These findings reveal that formation of metal coordination bonds to
      Cys7 and Cys60 play primary roles in transducing the allosteric response in CadC.
      The evolutionary implications for metal ion selectivity of ArsR/SmtB metal sensor
      proteins are discussed.

PMID- 12054864
TI  - Mediator factor Med8p interacts with the hexokinase 2: implication in the glucose
      signalling pathway of Saccharomyces cerevisiae.
AB  - In the presence of glucose the protein hexokinase 2 (Hxk2p), normally resident in
      the cytosol, is translocated to the nucleus where it impairs the activation of
      transcription of the glucose-repressed genes HXK1, GLK1 and SUC2, and promotes
      the activation of transcription of the glucose-induced genes HXK2 and HXT1. Here,
      we demonstrate the involvement of an heptameric motif, named the MED8 site, in
      the direct binding of the mediator protein Med8p, either as a monomer or as a
      homodimer. Because this site was previously involved in the Hxk2p-dependent
      glucose-induced regulation of gene transcription, we tested whether Hxk2p
      interacts with Med8p. Our results show that Hxk2 and Med8 proteins are physically
      associated and that this Hxk2p-Med8p interaction is of physiological significance
      because both proteins have been found interacting together in a cluster with DNA
      fragments containing the MED8 site. We conclude that Hxk2p operates through the
      MED8 site, by interacting with Med8p, in the glucose signal transduction pathway
      of Saccharomyces cerevisiae.

PMID- 12054865
TI  - Promoter of FGF8 reveals a unique regulation by unliganded RARalpha.
AB  - We previously reported that retinoids were inducing a complete switch in the
      expression of two isoforms from the fgf8 gene. In order to gain insight into the
      transcriptional mechanisms possibly involved in this regulation, we cloned and
      sequenced a fragment of genomic DNA encompassing 6 kb of the region 5' upstream
      of the fgf8 coding sequence and investigated its promoter elements. A
      comprehensive series of biochemical and cellular experiments determined two
      distinct functional regions cis-responsive to retinoids and/or their receptors:
      (i) a canonical RARE (type DR2) which is the cis target of a RARalpha-RXRalpha
      liganded heterodimer; and (ii) a completely novel type of response element
      composed of two half-binding sites separated by 87 nucleotides, which we
      demonstrate to be the target of an unliganded RARalpha homodimer phosphorylated
      on the Ser77 residue. Combined activities of these cis and trans-acting factors
      support a model of a complex regulation of fgf8 expression: by alternative
      binding to two distinct promoter elements, phosphorylated-unliganded-RARalpha
      homodimer or its liganded form have two distinct and mutually exclusive trans
      activating activities, explaining the expression of two different isoforms of
      fgf8.

PMID- 12054866
TI  - Detecting compensatory covariation signals in protein evolution using
      reconstructed ancestral sequences.
AB  - When protein sequences divergently evolve under functional constraints, some
      individual amino acid replacements that reverse the charge (e.g. Lys to Asp) may
      be compensated by a replacement at a second position that reverses the charge in
      the opposite direction (e.g. Glu to Arg). When these side-chains are near in
      space (proximal), such double replacements might be driven by natural selection,
      if either is selectively disadvantageous, but both together restore fully the
      ability of the protein to contribute to fitness (are together "neutral").
      Accordingly, many have sought to identify pairs of positions in a protein
      sequence that suffer compensatory replacements, often as a way to identify
      positions near in space in the folded structure. A "charge compensatory signal"
      might manifest itself in two ways. First, proximal charge compensatory
      replacements may occur more frequently than predicted from the product of the
      probabilities of individual positions suffering charge reversing replacements
      independently. Conversely, charge compensatory pairs of changes may be observed
      to occur more frequently in proximal pairs of sites than in the average pair.
      Normally, charge compensatory covariation is detected by comparing the sequences
      of extant proteins at the "leaves" of phylogenetic trees. We show here that the
      charge compensatory signal is more evident when it is sought by examining
      individual branches in the tree between reconstructed ancestral sequences at
      nodes in the tree. Here, we find that the signal is especially strong when the
      positions pairs are in a single secondary structural unit (e.g. alpha helix or
      beta strand) that brings the side-chains suffering charge compensatory
      covariation near in space, and may be useful in secondary structure prediction.
      Also, "node-node" and "node-leaf" compensatory covariation may be useful to
      identify the better of two equally parsimonious trees, in a way that is
      independent of the mathematical formalism used to construct the tree itself.
      Further, compensatory covariation may provide a signal that indicates whether an
      episode of sequence evolution contains more or less divergence in functional
      behavior. Compensatory covariation analysis on reconstructed evolutionary trees
      may become a valuable tool to analyze genome sequences, and use these analyses to
      extract biomedically useful information from proteome databases.

PMID- 12054867
TI  - Biochemical characterisation and genetic analysis of aureocin A53, a new,
      atypical bacteriocin from Staphylococcus aureus.
AB  - Aureocin A53 is produced by Staphylococcus aureus A53. It is encoded on a 10.4 kb
      plasmid, pRJ9, and is active against Listeria monocytogenes. Aureocin A53 is a
      highly cationic 51-residue peptide containing ten lysine and five tryptophan
      residues. Aureocin A53 was purified to homogeneity by hydrophobic-interaction,
      cation-exchange, and reverse-phase chromatography. MALDI-TOF mass spectrometry
      yielded a molecular mass of 6012.5 Da, which was 28 Da higher than predicted from
      the structural gene sequence of the bacteriocin. The mass increment resulted from
      an N-formylmethionine residue, indicating that the aureocin A53 is synthesised
      and secreted without a typical bacteriocin leader sequence or sec-dependent
      signal peptide. The structural identity of aureocin A53 was verified by Edman
      sequencing after de-blocking with cyanogen bromide and extensive mass
      spectrometry analysis of enzymatically and laser-generated fragments. The
      complete sequence of pRJ9 was determined and none of the open reading frames
      identified in the vicinity of the structural gene aucA showed similarity to genes
      that are typically found in bacteriocin gene clusters. Thus, neither a dedicated
      protease or transporter, nor modifying enzymes and regulatory elements seemed to
      be involved in the production of aureocin A53. Further unique features that
      distinguish aureocin A53 from other peptide bacteriocins include remarkable
      protease stability and a defined, rigid structure in aqueous solution.

PMID- 12054868
TI  - The catalytic mechanism of indole-3-glycerol phosphate synthase: crystal
      structures of complexes of the enzyme from Sulfolobus solfataricus with substrate
      analogue, substrate, and product.
AB  - Indoleglycerol phosphate synthase catalyzes the ring closure of an N-alkylated
      anthranilate to a 3-alkyl indole derivative, a reaction requiring Lewis acid
      catalysis in vitro. Here, we investigated the enzymatic reaction mechanism
      through X-ray crystallography of complexes of the hyperthermostable enzyme from
      Sulfolobus solfataricus with the substrate 1-(o-carboxyphenylamino) 1
      deoxyribulose 5-phosphate, a substrate analogue and the product indole-3-glycerol
      phosphate. The substrate and the substrate analogue are bound to the active site
      in a similar, extended conformation between the previously identified phosphate
      binding site and a hydrophobic pocket for the anthranilate moiety. This binding
      mode is unproductive, because the carbon atoms that are to be joined are too far
      apart. The indole ring of the bound product resides in a second hydrophobic
      pocket adjacent to that of the anthranilate moiety of the substrate. Although the
      hydrophobic moiety of the substrate moves during catalysis from one hydrophobic
      pocket to the other, the triosephosphate moiety remains rigidly bound to the same
      set of hydrogen-bonding residues. Simultaneously, the catalytically important
      residues Lys53, Lys110 and Glu159 maintain favourable distances to the atoms of
      the ligand undergoing covalent changes. On the basis of these data, the
      structures of two putative catalytic intermediates were modelled into the active
      site. This new structural information and the modelling studies provide further
      insight into the mechanism of enzyme-catalyzed indole synthesis. The charged
      epsilon-amino group of Lys110 is the general acid, and the carboxylate group of
      Glu159 is the general base. Lys53 guides the substrate undergoing conformational
      transitions during catalysis, by forming a salt-bridge to the carboxylate group
      of its anthranilate moiety.

PMID- 12054869
TI  - Redox-coupled conformational alternations in cytochrome c(3) from D. vulgaris
      Miyazaki F on the basis of its reduced solution structure.
AB  - Heteronuclear NMR spectroscopy was performed to determine the solution structure
      of (15)N-labeled ferrocytochrome c(3) from Desulfovibrio vulgaris Miyazaki F
      (DvMF). Although the folding of the reduced cytochrome c(3) in solution was
      similar to that of the oxidized one in the crystal structure, the region
      involving hemes 1 and 2 was different. The redox-coupled conformational change is
      consistent with the reported solution structure of D. vulgaris Hildenborough
      ferrocytochrome c(3), but is different from those of other cytochromes c(3). The
      former is homologous with DvMF cytochrome c(3) in amino acid sequence. Small
      displacements of hemes 1 and 2 relative to hemes 3 and 4 were observed. This
      observation is consistent with the unusual behavior of the 2(1)CH(3) signal of
      heme 3 reported previously. As shown by the (15)N relaxation parameters of the
      backbone, a region between hemes 1 and 2 has more flexibility than the other
      regions. The results of this work strongly suggest that the cooperative reduction
      of hemes 1 and 2 is based on the conformational changes of the C-13 propionate of
      heme 1 and the aromatic ring of Tyr43, and the interaction between His34 and His
      35 through covalent and coordination bonds.

PMID- 12054870
TI  - Crystal structure of shikimate kinase from Mycobacterium tuberculosis reveals the
      dynamic role of the LID domain in catalysis.
AB  - Shikimate kinase (SK) and other enzymes in the shikimate pathway are potential
      targets for developing non-toxic antimicrobial agents, herbicides, and anti
      parasite drugs, because the pathway is essential in the above species but is
      absent from mammals. The crystal structure of Mycobacterium tuberculosis SK
      (MtSK) in complex with MgADP has been determined at 1.8 A resolution, revealing
      critical information for the structure-based design of novel anti-M. tuberculosis
      agents. MtSK, with a five-stranded parallel beta-sheet flanked by eight alpha
      helices, has three domains: the CORE domain, the shikimate-binding domain (SB),
      and the LID domain. The ADP molecule is bound with its adenine moiety sandwiched
      between the side-chains of Arg110 and Pro155, its beta-phosphate group in the P
      loop, and the alpha and beta-phosphate groups hydrogen bonded to the guanidinium
      group of Arg117. Arg117 is located in the LID domain, is strictly conserved in SK
      sequences, is observed for the first time to interact with any bound nucleotide,
      and appears to be important in both substrate binding and catalysis. The crystal
      structure of MtSK (this work) and that of Erwinia chrysanthemi SK suggest a
      concerted conformational change of the LID and SB domains upon nucleotide
      binding.

PMID- 12054871
TI  - The structure of the soluble domain of an archaeal Rieske iron-sulfur protein at
      1.1 A resolution.
AB  - The first crystal structure of an archaeal Rieske iron-sulfur protein, the
      soluble domain of Rieske iron-sulfur protein II (soxF) from the hyperthermo
      acidophile Sulfolobus acidocaldarius, has been solved by multiple wavelength
      anomalous dispersion (MAD) and has been refined to 1.1 A resolution. SoxF is a
      subunit of the terminal oxidase supercomplex SoxM in the plasma membrane of S.
      acidocaldarius that combines features of a cytochrome bc(1) complex and a
      cytochrome c oxidase. The [2Fe-2S] cluster of soxF is most likely the primary
      electron acceptor during the oxidation of caldariella quinone by the cytochrome
      a(587)/Rieske subcomplex. The geometry of the [2Fe-2S] cluster and the structure
      of the cluster-binding site are almost identical in soxF and the Rieske proteins
      from eucaryal cytochrome bc(1) and b(6)f complexes, suggesting a strict
      conservation of the catalytic mechanism. The main domain of soxF and part of the
      cluster-binding domain, though structurally related, show a significantly
      divergent structure with respect to topology, non-covalent interactions and
      surface charges. The divergent structure of soxF reflects a different topology of
      the soxM complex compared to eucaryal bc complexes and the adaptation of the
      protein to the extreme ambient conditions on the outer membrane surface of a
      hyperthermo-acidophilic organism.

PMID- 12054872
TI  - The crystal structure of the olfactory marker protein at 2.3 A resolution.
AB  - Olfactory marker protein (OMP) is a highly expressed and phylogenetically
      conserved cytoplasmic protein of unknown function found almost exclusively in
      mature olfactory sensory neurons. Electrophysiological studies of olfactory
      epithelia in OMP knock-out mice show strongly retarded recovery following odorant
      stimulation leading to an impaired response to pulsed odor stimulation. Although
      these studies show that OMP is a modulator of the olfactory signal-transduction
      cascade, its biochemical role is not established. In order to facilitate further
      studies on the molecular function of OMP, its crystal structure has been
      determined at 2.3 A resolution using multiwavelength anomalous diffraction
      experiments on selenium-labeled protein. OMP is observed to form a modified beta
      clamshell structure with eight antiparallel beta-strands. While OMP has no
      significant sequence homology to proteins of known structure, it has a similar
      fold to a domain found in a variety of existing structures, including in a large
      family of viral capsid proteins. The surface of OMP is mostly convex and lacking
      obvious small molecule binding sites, suggesting that it is more likely to be
      involved in modulating protein-protein interaction than in interacting with small
      molecule ligands. Three highly conserved regions have been identified as leading
      candidates for protein-protein interaction sites in OMP. One of these sites
      represents a loop known to mediate ligand interactions in the structurally
      homologous EphB2 receptor ligand-binding domain. This site is partially buried in
      the crystal structure but fully exposed in the NMR solution structure of OMP due
      to a change in the orientation of an alpha-helix that projects outward from the
      structurally invariant beta-clamshell core. Gating of this conformational change
      by molecular interactions in the signal-transduction cascade could be used to
      control access to OMP's equivalent of the EphB2 ligand-interaction loop, thereby
      allowing OMP to function as a molecular switch.

PMID- 12054874
TI  - The activation energy for insertion of transmembrane alpha-helices is dependent
      on membrane composition.
AB  - The physical mechanisms that govern the folding and assembly of integral membrane
      proteins are poorly understood. It appears that certain properties of the lipid
      bilayer affect membrane protein folding in vitro, either by modulating helix
      insertion or packing. In order to begin to understand the origin of this effect,
      we investigate the effect of lipid forces on the insertion of a transmembrane
      alpha-helix using a water-soluble, alanine-based peptide,
      KKAAAIAAAAAIAAWAAIAAAKKKK-amide. This peptide binds to preformed 1,2-dioleoyl-l
      alpha-phosphatidylcholine (DOPC) vesicles at neutral pH, but spontaneous
      transmembrane helix insertion directly from the aqueous phase only occurs at high
      pH when the Lys residues are de-protonated. These results suggest that the
      translocation of charge is a major determinant of the activation energy for
      insertion. Time-resolved measurements of the insertion process at high pH
      indicate biphasic kinetics with time constants of ca 30 and 430 seconds. The
      slower phase seems to correlate with formation of a predominantly transmembrane
      alpha-helical conformation, as determined from the transfer of the tryptophan
      residue to the hydrocarbon region of the membrane. Temperature-dependent
      measurements showed that insertion can proceed only above a certain threshold
      temperature and that the Arrhenius activation energy is of the order of 90 kJ
      mol(-1). The kinetics, threshold temperature and the activation energy change
      with the mole fraction of 1,2-dioleoyl-l-alpha-phosphatidylethanolamine (DOPE)
      introduced into the DOPC membrane. The activation energy increases with
      increasing DOPE content, which could reflect the fact that this lipid drives the
      bilayer towards a non-bilayer transition and increases the lateral pressure in
      the lipid chain region. This suggests that folding events involving the insertion
      of helical segments across the bilayer can be controlled by lipid forces.

PMID- 12054873
TI  - Olfactory marker protein (OMP) exhibits a beta-clam fold in solution:
      implications for target peptide interaction and olfactory signal transduction.
AB  - Olfactory marker protein (OMP) is a ubiquitous, cytoplasmic protein found in
      mature olfactory receptor neurons of all vertebrates. Electrophysiological and
      behavioral studies demonstrate that it is a modulator of the olfactory signal
      transduction pathway. Here, we demonstrate that the solution structure of OMP, as
      determined by NMR studies, is a single globular domain protein comprised of eight
      beta-strands forming two beta-sheets oriented orthogonally to one another, thus
      exhibiting a "beta-clam" or "beta-sandwich" fold: beta-sheet 1 is comprised of
      beta3-beta8-beta1-beta2 and beta-sheet 2 contains beta6-beta5-beta4-beta7.
      Insertions include two, long alpha-helices located on opposite sides of the beta
      clam and three flexible loops. The juxtaposition of beta-strands beta6-beta5
      beta4-beta7-beta2-beta1-beta8-beta3 forms a continuously curved surface and
      encloses one side of the beta-clam. The "cleft" formed by the two beta-sheets is
      opposite to the closed end of the beta-clam. Using a peptide titration series, we
      have identified this cleft as the binding surface for a peptide derived from the
      Bex1 protein. The highly conserved Omega-loop structure adjacent to the Bex1
      peptide-binding surface found in OMP may be the site of additional OMP-protein
      interactions related to its role in modulating olfactory signal transduction.
      Thus, the interaction between the OMP and Bex1 proteins could facilitate the
      interaction between OMP and other components of the olfactory signaling pathway.

PMID- 12054876
TI  - Modern approaches in studying gene expression.

PMID- 12054877
TI  - Examining signaling specificity to transcription factors.
AB  - The activities of many transcription factors are controlled by intracellular
      signal transduction pathways that respond to changes in the extracellular
      environment. The resulting changes in gene expression lead to appropriate
      physiological responses. Elucidating the signaling pathways that target
      transcription factors is an important goal as they represent potential targets
      for therapeutic intervention in many diseases. A number of tools and techniques
      have been developed that can be used for studying signaling specificity toward
      transcription factors. This article describes how (1) mutant alleles of signaling
      enzymes and (2) protein/peptide inhibitors can be used in conjunction with
      phosphorylation-specific antibodies and reporter gene assays to examine the
      targeting of transcription factors by signaling pathways in vivo.

PMID- 12054878
TI  - Protein N-methyltransferase assays in the study of gene transcription.
AB  - Protein N-methylation has recently emerged as a major mechanism involved in
      regulating gene transcription and epigenetic inheritance. Transcriptional
      coactivators and corepressors have both been shown to associate with protein N
      methyltransferases. These enzymes methylate arginine or lysine residues within
      histones as well as other proteins, such as transcription factors. Here, we
      discuss the recent advances in our understanding of protein methylation and its
      involvement in gene expression. Protocols are presented for studying
      transcriptionally relevant protein methylation.

PMID- 12054879
TI  - In vitro assays to study protein ubiquitination in transcription.
AB  - Polyubiquitination is a death signal for proteins and condemns proteins to
      subsequent degradation by the 26S proteasome. However, recent studies imply that
      monoubiquitination and polyubiquitination of proteins do not necessarily result
      in protein degradation but play an important role in the execution of various
      biological events such as signal transduction and transcription. Ubiquitin was
      originally identified as a moiety attached to histones, and this as well as other
      histone modifications may play an important role for transcription and various
      other DNA-dependent processes. Considerable progress has been made in linking
      several histone modifications with chromatin dynamics in transcription.
      Acetylation of histones has been intimately linked to activation of
      transcription, while deacetylation is concomitant with repression of
      transcription. Although other histone modifications such as methylation,
      phosphorylation, and ubiquitination have been correlated with transcriptionally
      competent or inactive chromatin, the enzymes that mediate these modifications are
      only now being discovered. The identification of these histone-modifying enzymes
      may provide valuable insights into the role and function of histone modifications
      such as ubiquitination in transcription as well as other DNA-dependent processes.
      Recently, we have used various in vitro assays to show that the coactivator
      TAF(II)250 possesses both ubiquitin-activating and ubiquitin-conjugating
      activities, which monoubiquitinate histone H1. Here, we describe the methods used
      to identify this bifunctional enzyme: (1) in-gel activity assay; (2) protein
      transfer membrane activity assay; and (3) in-solution activity assay. These
      methods have been successfully used to identify various histone-modifying enzymes
      and protein kinases. In this article we contribute a short review of the history
      of the methods used to study ubiquitination of proteins and histone modification.
      We provide protocols for in-gel, protein-transfer membrane, and in-solution
      ubiquitination assays. A discussion of the general use of the provided protocols,
      their limitations, and future perspectives are presented. The described methods
      provide useful tools for the identification of not only novel histone-modifying
      enzymes but also other protein-modifying enzymes that act in a variety of
      biological events.

PMID- 12054880
TI  - Assays for the identification and evaluation of histone acetyltransferase
      inhibitors.
AB  - There is presently enormous interest in the function and regulatory roles of
      histone acetyltransferase enzymes. Along with deacetylases it is now evident that
      these enzymes play a key role in many cellular processes including chromatin
      remodeling and gene transcription. As such, effective small molecule enzyme
      inhibitors would be useful tools for molecular pharmacology and may also be
      suitable for further development into agents for the treatment of diseases such
      as cancer. A high-throughput assay based on the use of scintillating microplates
      (FlashPlates) suitable for screening libraries of compounds for inhibitors of
      acetylase activity is described here. Confirmation of activity of selected
      compounds is achieved with a conventional filter assay, the details of which are
      also described. In addition, an assay suitable for confirming that cellular
      protein acetylation has been altered by inhibition of acetylases or deacetylases
      is also presented. On the same plate, cells are grown, exposed to compound,
      fixed, and permeabilized, and protein acetylation is determined using standard
      ELISA methodology and a europium-labeled second antibody. This latter method
      provides a medium-throughput alternative to the use of immunoblotting for
      mechanistic studies.

PMID- 12054881
TI  - Immunoprecipitation techniques for the analysis of transcription factor
      complexes.
AB  - Interactions among transcription factors can be detected and analyzed by a
      variety of in vitro and in vivo approaches. In many studies, the existence of
      putative interactions among transcription factor partners is initially
      established from yeast two-hybrid screening and in vitro protein association
      analysis. The ability to detect candidate interacting proteins in
      coimmunoprecipitates from cell lysates provides an important criterion for
      establishing the authenticity of such protein interactions in vivo. This article
      describes methodology developed for detecting interactions between the helix-loop
      helix protein, Id3, and the paired homeodomain protein, Pax5, and interactions
      involving the zinc finger transcription factor, CTCF. The importance of
      empirically establishing optimum conditions for cell lysis, selection of
      appropriate antibodies, conditions for immunoprecipitation, and detection of
      interacting partners are discussed.

PMID- 12054882
TI  - Isolation and mass spectrometry of transcription factor complexes.
AB  - Protocols are described that enable the isolation of novel proteins associated
      with a known protein and the subsequent identification of these proteins by mass
      spectrometry. We review the basics of nanosample handling and of two
      complementary approaches to mass analysis, and provide protocols for the entire
      process. The protein isolation procedure is rapid and based on two high-affinity
      chromatography steps. The method does not require previous knowledge of complex
      composition or activity and permits subsequent biochemical characterization of
      the isolated factor. As an example, we provide the procedures used to isolate and
      analyze yeast Elongator, a histone acetyltransferase complex important for
      transcript elongation, which led to the identification of three novel subunits.

PMID- 12054883
TI  - The use of inducible engrailed fusion proteins to study the cellular functions of
      eukaryotic transcription factors.
AB  - Transcription factors determine cell lineages, control cell fate, and regulate
      cellular responses to stimuli. Many methods are currently used to study the
      function of transcription factors in a cellular context and several of these
      involve overexpressing a constitutively active form of the protein and studying
      its effects. Here we outline an alternative approach involving the inducible
      expression of dominant-negative transcription factors in human cell lines.
      Dominant-negative transcription factors can be used to investigate the effect of
      signaling pathways on complex cellular processes that are regulated by a
      particular transcription factor. Potent dominant-negative transcription factors
      can be created by using fusions to the engrailed repressor domain. These fusion
      proteins can be coupled to inducible expression systems such as the ecdysone
      inducible system. The ability to control protein expression has several benefits
      including the ability to create stable cell lines that express potentially
      cytotoxic proteins. Therefore when used in tandem, these two methods constitute a
      new and improved approach for dissecting the cellular role and transcriptional
      targets of many transcription factors. Here we illustrate this integrated
      approach by using a conditional dominant-negative Elk-1 protein to identify
      candidate Elk-1-regulated target genes.

PMID- 12054884
TI  - Hybridization array technology coupled with chemostat culture: Tools to
      interrogate gene expression in Saccharomyces cerevisiae.
AB  - Hybridization array technology is increasingly being used for the analysis of
      gene expression in the yeast Saccharomyces cerevisiae. It is a powerful technique
      in which the relative abundance of all the mRNA molecules transcribed under a
      particular condition may be simultaneously measured. However, most studies
      performed using this technique are carried out in batch culture where the growth
      rate and environment are continuously changing. Often, the experimental condition
      being studied also impacts on the growth rate of the cells. Changes in growth
      rate affect the pattern of gene expression. Consequently, the analysis and
      interpretation of experimental results obtained in this way are inherently
      problematic due to the difficulty in discriminating between effects due to the
      experimental condition per se and concomitant growth rate-related effects. Here,
      we present a method that addresses this problem by exploiting chemostat culture,
      in which the cells can be grown at a fixed growth rate, in combination with
      hybridization array technology. We use two experimental examples to illustrate
      the advantages of using this approach and then describe a specific application of
      this approach to investigate the effect of carbon and nitrogen limitation at the
      transcriptome level.

PMID- 12054885
TI  - RNA-protein interactions: insight into gene function.

PMID- 12054886
TI  - Kinetic studies of RNA-protein interactions using surface plasmon resonance.
AB  - Although structural, biochemical, and genetic studies have provided much insight
      into the determinants of specificity and affinity of proteins for RNA, little is
      currently known about the kinetics that underlie RNA-protein interactions.
      Protein-RNA complexes are dynamic, and the kinetics of binding and release could
      influence many processes, such as the ability of RNA-binding proteins to compete
      for binding sites, the sequential assembly of ribonucleoprotein complexes, and
      the ability of bound RNA to move between cellular compartments. Therefore, to
      attain a complete and biologically relevant understanding of RNA-protein
      interactions, complex formation must be studied not only in equilibrated
      reactions, but also as a dynamic process. BIACORE, a surface plasmon resonance
      based biosensor technology, allows intermolecular interactions to be measured in
      real time, and can provide both equilibrium and kinetic information about complex
      formation. This technology is a powerful tool with which to study the dynamics of
      RNA-protein interactions. We have used BIACORE extensively to obtain detailed
      insight into the interaction between RNA and proteins carrying RNA recognition
      motif domains. Here we discuss the physical principles on which BIACORE is based,
      and the required instrumentation. We describe how to design well-controlled RNA
      protein interaction experiments aimed at yielding high-quality data, and outline
      the steps required for data analysis. In addition, we present examples to
      illustrate how kinetic studies have provided us with unique insights into the
      interaction of the spliceosomal U1A protein and the neuronal HuD protein with
      their respective RNA targets.

PMID- 12054887
TI  - Toeprint analysis of the positioning of translation apparatus components at
      initiation and termination codons of fungal mRNAs.
AB  - The ability to map the position of ribosomes and their associated factors on
      mRNAs is critical for an understanding of translation mechanisms. Earlier
      approaches to monitoring these important cellular events characterized nucleotide
      sequences rendered nuclease-resistant by ribosome binding. While these approaches
      furthered our understanding of translation initiation and ribosome pausing, the
      pertinent techniques were technically challenging and not widely applied. Here we
      describe an alternative assay for determining the mRNA sites at which ribosomes
      or other factors are bound. This approach uses primer extension inhibition, or
      "toeprinting," to map the 3' boundaries of mRNA-associated complexes. This
      methodology, previously used to characterize initiation mechanisms in prokaryotic
      and eukaryotic systems, is used here to gain an understanding of two interesting
      translational regulatory phenomena in the fungi Neurospora crassa and
      Saccharomyces cerevisiae: (a) regulation of translation in response to arginine
      concentration by an evolutionarily conserved upstream open reading frame, and (b)
      atypical termination events that occur as a consequence of the presence of
      premature stop codons.

PMID- 12054888
TI  - Identifying mRNAs bound by RNA-binding proteins using affinity purification and
      differential display.
AB  - Many methods are available and widely used to determine specific proteins that
      bind to a particular RNA of interest. However, approaches to identify unknown
      substrate RNAs to which an RNA-binding protein binds and potentially regulates
      are not as common. In this article we describe a technique termed isolation of
      specific nucleic acids associated with proteins (SNAAP) that allows the
      identification of mRNAs associated with a protein. Methods are detailed for
      expressing and purifying fusion proteins that are used to isolate substrate mRNPs
      employing differential display technology. Lastly, experiments are described to
      confirm that the RNAs identified are indeed bonafide substrates for an RNA
      binding protein. As the number of known RNA-binding proteins increases, of which
      many are involved in genetic disorders, it is essential that methodologies exist
      to identify RNA-protein interactions to better understand the manifestation of
      disease.

PMID- 12054889
TI  - Analyzing mRNA-protein complexes using a yeast three-hybrid system.
AB  - RNA-protein interactions are essential for the proper execution and regulation of
      every step in the life of a eukaryotic mRNA. Here we describe a three-hybrid
      system in which RNA-protein interactions can be analyzed using simple phenotypic
      or enzymatic assays in Saccharomyces cerevisiae. The system can be used to detect
      or confirm an RNA-protein interaction, to analyze RNA-protein interactions
      genetically, and to discover new protein or RNA partners when only one is known.
      Multicomponent complexes containing more than one protein can be detected,
      identified, and analyzed. We describe the method and how to use it, and discuss
      applications that bear particularly on eukaryotic mRNAs.

PMID- 12054890
TI  - Tethered function assays using 3' untranslated regions.
AB  - Proteins that regulate mRNA metabolism are often bipartite: an RNA binding
      activity confers substrate specificity, and a "functional" domain elicits the
      biological outcome. In some cases, these two activities reside on different
      polypeptides that form a complex on the mRNA. Regardless, experimental separation
      of RNA binding from function facilitates analysis of both properties, liberating
      each from the constraints of the other. "Tethered function" assays bring a
      protein to a reporter RNA through a designed RNA-protein interaction. The
      function of the tethered protein-whether that be stability, translation,
      localization, or transport, or otherwise-is then assessed. We refer to this
      approach as a "tethered function" assay, since it can be examined. The approach
      does not require knowledge of the natural RNA binding sites, or of the
      composition of the naturally occurring protein complexes. It can be useful in
      dissecting how proteins that act on RNAs work, and in identifying active
      components of multiprotein complexes. RNA-binding proteins previously have been
      linked to foreign RNA-binding specificities, for a wide variety of purposes. We
      emphasize here the particular value of tethering to the 3' untranslated region of
      eukaryotic mRNAs, and the opportunities it presents for the analysis of how those
      mRNAs are regulated. We discuss experimental design, as well as published and
      potential applications.

PMID- 12054891
TI  - Identifying proteins that affect mRNA localization in living cells.
AB  - Messenger RNA transport has emerged as a significant mechanism for regulating
      gene expression. Many of the protein factors affecting RNA transport remain
      unknown. The emergence of green fluorescent protein (GFP) fluorescence microscopy
      allows imaging in living cells and an increased understanding of in vivo
      molecular transport. GFP imaging is now applied to RNA transport by engineering
      RNA hairpins into the RNA of interest and observing fluorescence from GFP fused
      to an RNA-binding protein that recognizes the hairpins. In yeast, different
      genetic backgrounds can be tested to identify various proteins that affect RNA
      transport and localization. The technology also allows the swapping of different
      regions of the RNA to determine the cis requirements for transport. GFP RNA
      imaging opens many possibilities to examine RNA transport in real time in a
      variety of different organisms.

PMID- 12054892
TI  - RNA affinity tags for purification of RNAs and ribonucleoprotein complexes.
AB  - Intrinsic affinity tags are useful tools for the study of macromolecular targets.
      Although polypeptide affinity tags are routinely used in purification and
      detection of protein complexes, there has been a relative lack of powerful RNA
      affinity tags that can be embedded within RNA sequences. Here, the preparation
      and use of two RNA affinity tags against Sephadex or streptavidin are described.
      The two tags have different strengths that make them appropriate for slightly
      different uses. One is a high-affinity ligand for streptavidin that can be
      specifically eluted by competition with biotin under otherwise native binding
      conditions. The other tag binds selectively to Sephadex beads, and can be eluted
      by competition with the soluble dextran that composes Sephadex. When properly
      placed within another RNA molecule, the tags can be used to effect dramatic
      purification of RNA or ribonucleoprotein complexes from complex mixtures of
      cellular RNA.

PMID- 12054893
TI  - Analysis of RNA-protein complexes by oligonucleotide-targeted RNase H digestion.
AB  - Oligonucleotide-targeted RNase H protection assays are powerful means to analyze
      protein binding domains in ribonucleoprotein particles (RNPs). In such an assay,
      the RNA component of a RNP and, in an essential control reaction, the
      corresponding deproteinized RNA are targeted with an antisense DNA
      oligonucleotide and RNase H. If the oligonucleotide is able to anneal to the
      complementary sequence of the RNA, RNase H will cleave the RNA within the double
      stranded DNA/RNA region. However, protein binding to a specific RNA sequence may
      prevent hybridization of the DNA oligonucleotide, thereby protecting the RNA
      molecule from endonucleolytic cleavage. An RNase H protection analysis can
      usually be carried out with crude cell extract and does not require further RNP
      purification. On the other hand, purified RNP fractions are preferable when a
      crude extract contains RNase activity or a heterogenous RNP population of a
      specific RNA. The cleavage pattern of RNase H digestion can be analyzed by
      Northern blotting or primer-extension assays. In addition, the investigation of
      RNP fragments, for example, by native gel electrophoresis, may reveal important
      structural information about a RNP. In this article, we describe procedures for
      RNP and RNA preparation, the oligonucleotide-targeted RNase H protection assay,
      and methods for the analysis of RNA and RNP cleavage products. As an example, we
      show oligonucleotide-targeted RNase H protection of the Trypanosoma brucei U1
      small nuclear RNP.

PMID- 12054894
TI  - A two-tracked approach to analyze RNA-protein crosslinking sites in native,
      nonlabeled small nuclear ribonucleoprotein particles.
AB  - Much attention is currently being devoted to questions of protein and RNA
      tertiary structures and to the quaternary arrangement of the individual
      macromolecules in ribonucleoprotein (RNP) particles. In this article we describe
      two complementary strategies that allow the identification of RNA-protein contact
      sites in assembled, nonlabeled RNP particles after UV crosslinking. The first
      combines immunoprecipitation of UV-irradiated RNP particles under mildly
      denaturing conditions followed by primer-extension analysis of the crosslinked
      (and thus coprecipitated) RNA. The second involves the purification of
      crosslinked peptide-oligonucleotide from RNP particles and the subsequent
      analysis of the crosslinked peptide and RNA by Edman degradation and matrix
      assisted laser desorption/ionization (MALDI)-mass spectrometry (MS),
      respectively. Although the first approach provides a rapid method for the exact
      identification of RNA-protein contact sites in purified nonlabeled RNP particles,
      the latter adds valuable information about potential RNA binding domains within
      proteins and, thus, about the arrangement of these proteins within the quaternary
      structures of complex RNP assemblies. Recently, we applied both these strategies
      successfully to native purified spliceosomal RNP. These methods may be generally
      applicable to the analysis of RNP complexes, especially as they avoid labeling
      and reconstitution, both of which risk introducing artifacts.

PMID- 12054895
TI  - Reversible cross-linking combined with immunoprecipitation to study RNA-protein
      interactions in vivo.
AB  - Protein-RNA interactions play indispensable structural, catalytic, and regulatory
      roles within the cell. Understanding their physical association in vivo provides
      valuable insight into their assembly, function, and regulation in the cellular
      milieu. Inspired by the chromatin immunoprecipitation assay, we have developed a
      ribonucleoprotein (RNP) immunoprecipitation assay to study RNA-protein
      interactions in vivo. This method takes advantage of the highly reactive,
      reversible crosslinker formaldehyde, combined with high-stringency
      immunoprecipitation to identify specific RNAs associated with a given protein.
      The RNP immunoprecipitation (RIP) assay was developed using RNA-protein
      interactions of hepatitis delta virus (HDV) as a model system. HDV is an RNA
      virus with a single-stranded circular RNA genome that encodes one viral protein,
      hepatitis delta antigen (HDAg). The high affinity of HDAg for the HDV RNA genome,
      combined with the well-characterized anti-HDAg antibodies, made this system a
      logical starting point for the development of the RIP assay. Cells with
      replicating HDV were crosslinked with formaldehyde and the HDV RNPs were
      immunoprecipitated using anti-HDAg antibodies. The crosslinks were then reversed
      by heat treatment, and the immunoprecipitated HDV RNAs were identified by reverse
      transcription polymerase chain reaction (RT-PCR). The specificity of this assay
      was tested using HDV mutants and heterologous antibodies for immunoprecipiation
      followed by RT-PCR with HDV-specific primers. This experiment showed no
      nonspecific immunoprecipitation of the HDV RNPs. The method was tested further
      using protein-RNA interactions known to exist in the U1 snRNP. The results
      indicate that the RIP assay is a powerful tool to identify RNA-protein
      interactions in vivo and has the potential to unravel the cellular network of RNP
      complexes in their native setting.

PMID- 12054896
TI  - Ribonomics: identifying mRNA subsets in mRNP complexes using antibodies to RNA
      binding proteins and genomic arrays.
AB  - Although in vitro methods have been used to identify putative targets of mRNA
      binding proteins, direct in vivo methods are needed to identify endogenously
      associated mRNAs and their cognate proteins. Therefore, we have developed high
      throughput methods to identify structurally and/or functionally related mRNA
      transcripts through their endogenous association with RNA-binding proteins. We
      have termed the identification and analysis of mRNA subsets using RNA-associated
      proteins ribonomics, and have established four primary steps for the method: (1)
      isolation of endogenous mRNA-protein complexes (mRNPs) under optimized
      conditions, (2) the en masse characterization of the protein and mRNA components
      associated with the targeted mRNP complexes, (3) identification of sequences or
      structural similarities among members of the mRNA subset, and (4) determination
      of functional relationships among the protein products coded for by members of
      the mRNA subset. We have hypothesized that mRNAs are organized into structurally
      and functionally linked groups to better affect information transfer through
      coordinate gene expression. The functional consequences of such organization
      would be to facilitate the production of proteins that regulate processes
      necessary for growth and differentiation. This article describes a series of
      biochemical techniques that deal with the first two steps of ribonomic profiling:
      purifying endogenous mRNP complexes and identifying multiple mRNA targets using
      microarray analysis.

PMID- 12054897
TI  - Analysis of gene function in somatic mammalian cells using small interfering
      RNAs.
AB  - RNA interference (RNAi) is a highly conserved gene silencing mechanism that uses
      double-stranded RNA (dsRNA) as a signal to trigger the degradation of homologous
      mRNA. The mediators of sequence-specific mRNA degradation are 21- to 23-nt small
      interfering RNAs (siRNAs) generated by ribonuclease III cleavage from longer
      dsRNAs. Twenty-one-nucleotide siRNA duplexes trigger specific gene silencing in
      mammalian somatic cells without activation of the unspecific interferon response.
      Here we provide a collection of protocols for siRNA-mediated knockdown of
      mammalian gene expression. Because of the robustness of the siRNA knockdown
      technology, genomewide analysis of human gene function in cultured cells has now
      become possible.

PMID- 12054898
TI  - In vivo assays to examine transcription factor localization and target gene
      specificity.

PMID- 12054899
TI  - Localizing transcription factors on chromatin by immunofluorescence.
AB  - This article contains a detailed protocol for localizing transcription factors on
      Drosophila melanogaster polytene chromosomes by immunofluorescence. The large
      polytene chromosomes from third-instar larval salivary gland cells allow mapping
      of chromosome-associated proteins at high resolution. Thus, this method has been
      used to investigate how broadly transcription factors function and to identify
      and characterize cis-acting protein domains, trans-acting proteins, and trans
      acting DNA elements that are necessary for chromosomal association of
      transcription factors. The ability to directly visualize transcription factors
      bound to chromosomes during a transcriptionally active stage of the cell cycle
      has greatly enhanced our understanding of how transcription factors function in
      vivo.

PMID- 12054900
TI  - Visualizing nuclear proteins together with transcribed and inactive genes in
      structurally preserved cells.
AB  - Recent data support the idea that the mammalian nucleus is organized in a
      functionally significant way. Immunocytochemistry has revealed the existence of
      diverse nuclear "bodies" and compartments. Fluorescence in situ hybridization
      (FISH) has shown that chromosomes change their spatial relationships during
      dynamic cell cycle progression and that nuclear organization can change during
      development and differentiation when patterns of gene expression are established
      or modified. To determine the relationship between nuclear organization and
      genome function is an important goal for biology. This article describes an
      immunoFISH technique, which is a useful tool for investigating the functional
      organization of the nucleus. It combines immunocytochemistry with FISH to allow
      associations between proteins, DNA, and RNA to be visualized in a single-step
      analysis using confocal microscopy. Immunocytochemistry and FISH were thought
      incompatible since cell preparation flattens nuclei and the harsh DNA
      denaturation treatment required for FISH destroys proteins. The immunoFISH
      technique successfully overcomes these problems and can reveal interactions
      between nuclear components not readily detectable using other experimental
      approaches. The interactions of single-copy, endogenous loci with nuclear
      proteins or bodies can be seen, as can spatial compartmentalization of these
      loci, in cells preserved in three dimensions, representative of the situation in
      vivo. Allelic differences in transcription can be related to nuclear location and
      protein interactions of the individual alleles since genes, RNA and proteins can
      be visualized together. Chromosome behavior can be followed through mitosis to
      investigate centromere activity or vector segregation efficiency, for example.
      Visual data obtained using the immunoFISH technique have provided insight into
      the functional significance of nuclear organization and its role in cell biology.

PMID- 12054901
TI  - Allele-specific analysis of transcription factors binding to promoter regions.
AB  - In vivo footprinting techniques are useful for the identification of regulatory
      elements mediating transcriptional control of a gene. However, regulation of a
      gene can differ between the two alleles, and further steps must be taken to
      distinguish between the regulatory elements occupied on one allele and those used
      on the second allele. Many hematologic malignancies result from chromosomal
      translocations, which, in some cases, relocate a gene to a transcriptionally
      active region leading to the deregulated expression of that gene. This situation
      provides an example of differential expression between two alleles. In studying
      the t(14; 18) and t(8; 14) translocations, which involve the bcl-2 and c-myc
      proto-oncogenes, respectively, we have been able to identify regulatory elements
      important in mediating the activation of the translocated alleles and the
      silencing of the normal alleles. Following in vivo methylation and isolation of
      genomic DNA, we were able to separate the translocated and normal alleles by
      electrophoresis. Using the ligation-mediated polymerase chain reaction (LMPCR)
      technique, we could then assess protein interactions on the two different
      alleles. A detailed description of this methodology with examples from our
      studies are provided with a discussion of how these techniques may be applied to
      the study of other genes.

PMID- 12054902
TI  - Dissecting long-range transcriptional mechanisms by chromatin
      immunoprecipitation.
AB  - Analysis of physiological mechanisms that control transcription often requires
      extrapolation of in vitro measurements into in vivo mechanisms. This
      extrapolation is complex, as mammalian genes are commonly organized into broad
      chromosomal domains, and such domains cannot be readily reconstituted in vitro.
      Thus, the nucleoprotein structure of chromosomes constitutes a considerable
      impediment to elucidating transcriptional mechanisms. The development of assays
      to measure protein-DNA interactions and chromatin structure in living cells has
      greatly facilitated progress in understanding physiological transcriptional
      mechanisms. Chromatin immunoprecipitation (ChIP) is a powerful approach that
      allows one to define the interaction of factors with specific chromosomal sites
      in living cells, thereby providing a snapshot of the native chromatin structure
      and factors bound to genes in different functional states. ChIP involves treating
      cells or tissue briefly with formaldehyde to crosslink proteins to DNA. An
      antibody against a protein suspected of binding a given cis-element is then used
      to immunoprecipitate chromatin fragments. Polymerase chain reaction analysis of
      the immunoprecipitate with primers flanking the cis-element reveals whether a
      specific DNA sequence is recovered in an immune-specific manner and therefore
      whether the protein contacted the site in living cells. The central focus of this
      review is the use of ChIP to study transcriptional activation over long distances
      on chromosomes.

PMID- 12054903
TI  - Identification of unknown target genes of human transcription factors using
      chromatin immunoprecipitation.
AB  - The standard chromatin immunoprecipitation (ChIP) assay is used to examine the
      specific association of transcription factors with DNA in the context of living
      cells. Here we review two modifications to this protocol which are designed to
      identify novel target genes of transcription factors in mammalian cells. The main
      advantage to both of these approaches is that only DNA sequences directly bound
      by a factor within the context of a living cell will be identified. Therefore,
      artifacts associated with overexpression and/or alterations in signaling pathways
      are avoided. The first modification we describe, a ChIP cloning strategy, can be
      used to isolate any genomic fragment specifically associated with a particular
      factor. It requires no special equipment or reagents other than a high-affinity
      antibody to be used for immunoprecipitation of the factor of interest. However,
      it is most useful for the isolation of a small number of genomic targets. In
      contrast, the second modification, which combines ChIP with specialized CpG
      microarrays, is ideal for a more global analysis of target genes. Advantages,
      common problems, and detailed protocols for these two ChIP techniques are
      discussed.

PMID- 12054904
TI  - Characterizing transcription factor binding sites using formaldehyde crosslinking
      and immunoprecipitation.
AB  - In their article, A.S. Weinmann and P.J. Farnham (2002, Methods 26) described new
      techniques for isolating in vivo binding sites for any DNA-binding protein. In
      this article, we describe complementary methods for detailed in vivo
      characterizations of such identified protein-DNA interactions. First, we describe
      how formaldehyde crosslinking and chromatin immunoprecipitation (ChIP), in
      conjunction with transient transfections or the use of cell lines containing
      stably integrated constructs or episomes, can be employed to identify which
      specific nucleotides of a region of DNA are required for recruitment of a
      particular transcription factor. In contrast to in vivo footprinting, this method
      not only specifies which nucleotides are bound, but also identifies the
      protein(s) involved in binding. Next, we discuss the use of the ChIP assay to
      study how binding of a transcription factor is altered by passage through the
      cell cycle, by overexpression or deletion of another factor, or during
      tumorigenesis. Finally, a look toward the future suggests that the ChIP assay may
      be combined with Western blot analysis or mass spectrometry to identify
      additional proteins that interact with a transcription factor of interest.

PMID- 12054905
TI  - Identification and characterization of transcription factor target genes using
      gene-targeted mice.
AB  - Critical to understanding biological roles for transcription factors is an
      appreciation of the target genes regulated by the transcription factor. The
      identification of target genes can often expand the understanding of known
      biological roles for a transcription factor and may reveal unappreciated and
      unexpected functions. This article focuses on the identification and
      characterization of transcription factor target genes using mouse molecular
      genetics. The use of genetically engineered (knockout) mice and global gene
      expression analysis to identify transcription factor target genes is reviewed,
      with emphasis on important technical considerations. Detailed protocols for the
      application of real-time reverse transcription polymerase chain reaction and
      immunohistochemistry in target gene expression analysis are described. The
      article closes with a discussion of the use of mouse molecular genetics for the
      characterization of target genes as downstream effectors of transcription
      factors.

PMID- 12054906
TI  - The use of zinc finger peptides to study the role of specific factor binding
      sites in the chromatin environment.
AB  - The once ambitious goal of creating custom DNA-binding factors has been achieved.
      Advances in construction methodology now enable any laboratory to create site
      specific binding proteins to nearly any sequence. Using predefined zinc finger
      modules, new proteins can be constructed in days with minimal cost and using only
      standard polymerase chain reaction techniques. The existing spectrum of modules
      can be rearranged to produce more than one billion different proteins that bind
      with high affinity and specificity. Artificial transcription factors based on
      modified zinc finger domains have recently been shown by several groups to be
      capable of activating or repressing transcription of a handful of endogenous
      genes in the chromatin environment of plant and animal cells. These proteins can
      also be used in a number of ways to compete with endogenous factors for specific
      binding sites in vivo. Zinc finger peptides are therefore useful tools in the
      study of gene regulation and signal transduction. A detailed description of the
      construction method is presented, along with a full discussion of potential
      caveats and future expectations.

PMID- 12054907
TI  - The use of altered specificity mutants to probe specific protein-protein
      interactions involved in the activation of GATA-1 target genes.
AB  - With the increasing popularity of the yeast two-hybrid screen, a large number of
      protein-protein interactions have been identified. In many cases, single proteins
      have been found to associate with a large number of cofactors. For example, the
      hematopoietic transcription factor GATA-1 interacts with a multitude of other
      nuclear proteins, including Friend of GATA-1 (FOG-1), EKLF, CBP/p300, and Lmo2.
      Furthermore, p300, besides associating with GATA-1, interacts with at least seven
      other hematopoietic transcription factors. Despite the numerous pairwise and
      higher-order interactions identified, assessment of their contribution to
      transcriptional control has been lacking. Here we describe a strategy that can be
      applied to assess the functional relevance of any protein-protein association.
      This approach involves the creation of altered specificity mutants though the use
      of a combination of two yeast two-hybrid screens. Once altered specificity
      factors are obtained, a researcher can then proceed to functional assays that
      address the role of a specific protein-protein interaction.

PMID- 12054908
TI  - How blind is double-blind? A study of fish oil versus placebo.
AB  - The distinctive aftertaste associated with fish oil preparations used in clinical
      trials of omega-3 fatty acids may weaken the double-blind. This double-blind
      pilot study was designed to examine whether normal subjects could correctly
      'guess' if they were receiving capsules containing concentrated fish oil or
      capsules of pure olive oil. The informed consent was designed to give subjects
      ambiguous expectations about what oil they might be receiving to examine whether
      this would influence their guess. Despite a marked difference in taste
      experience, there was no significant difference in correct guesses between the
      two groups. The results suggest that altering subjects' expectations could
      further improve the validity of the double-blind.

PMID- 12054909
TI  - Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic
      beverage-induced bronchoconstriction in asthmatic patients.
AB  - Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The
      thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits
      acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study
      evaluated the involvement of TXA(2) on alcoholic beverage-induced
      bronchoconstriction. Four patients with alcohol-induced asthma received ozagrel
      (400 mg for 4 days) or placebo using a single-blind, randomized, cross-over
      design. On two separate study days, each subject drank the same brand and volume
      of alcoholic beverage (beer or Japanese sake) and bronchoconstriction was
      assessed as the change in peak expiratory flow (PEF). The effect of ozagrel on
      the aerosolized challenge of acetaldehyde was investigated in the same subjects.
      Although aerosolized acetaldehyde-induced bronchoconstriction was significantly
      prevented by ozagrel, there were no differences in the time course of the
      decrease in PEF or the maximum fall in PEF after alcohol intake between placebo
      and ozagrel. We conclude that TXA(2) is not involved in alcoholic beverage
      induced bronchoconstriction.

PMID- 12054910
TI  - Investigations into the mechanisms controlling prostaglandin production by the
      guinea-pig placenta: roles of calcium and gonadotrophin-releasing hormone.
AB  - The outputs of PGF(2 alpha), PGE(2) and 6-keto-PGF(1 alpha) were higher from the
      day 29 guinea-pig placenta than from the sub-placenta in culture, with PGF(2
      alpha)being the major prostaglandin produced by the placenta. Lack of
      extracellular calcium reduced the production of all three prostaglandins by the
      sub-placenta and 6-keto-PGF(1 alpha) production by the placenta, but had no
      effect on the production of PGF(2 alpha) and PGE(2) by the placenta. EGTA (a
      calcium chelator) and a low concentration (30 microM) of TMB-8 (an intracellular
      calcium antagonist) generally inhibited prostaglandin output from the placenta
      and sub-placenta at various time points during culture, although EGTA had no
      effect on PGE(2) output from the placenta. Trifluoperazine and W-7 (calmodulin
      inhibitors) had no inhibitory effect on the outputs of PGF(2 alpha) and PGE(2)
      from the placenta, nor on the outputs of any prostaglandin from the sub-placenta.
      However, these two compounds inhibited the output of 6-keto-PGF(1 alpha) from the
      placenta. Nifedipine and verapamil (calcium channel blocking drugs) generally
      reduced the outputs of prostaglandins from the placenta and sub-placenta, except
      verapamil had no inhibitory effect on PGF(2 alpha) output from the sub-placenta.
      Gonadotrophin-releasing hormone (GnRH) did not stimulate the output of
      prostaglandins from the placenta, and tended to have a weak inhibitory action on
      this tissue. On the sub-placenta, GnRH had an initial inhibitory action on the
      outputs of PGF(2alpha) and 6-keto-PGF(1 alpha), which was then followed by a
      stimulation of the outputs of PGF(2 alpha) and, to a lesser extent, of PGE(2).

PMID- 12054911
TI  - Prostaglandin E(2) 9-keto reductase activity in bovine retained and not retained
      placenta.
AB  - Prostaglandin E(2) 9-keto reductase (9-KPR) activity shifts reversibly PGE(2)
      into PGF(2 alpha) and may be responsible for the control of prostaglandins (PGs)
      levels in, among others, placental tissues. The retention of fetal membranes in
      cows is the postpartum disorder where the disturbances in PGs metabolism have
      been reported. It has been argued whether these disturbances are due to
      alterations in 9-KPR activity. In this study, the activity of the enzyme was
      determined in maternal and fetal bovine placental tissues which were divided into
      6 groups as follows: (A) caesarian section before term without retained fetal
      membranes (n=10), (B) caesarian section before term with retained fetal membranes
      (n=10), (C) caesarian section at term without retained fetal membranes (n=12),
      (D) caesarian section at term with retained fetal membranes (n=12), (E)
      spontaneous delivery at term without retained fetal membranes (n=12), (F)
      spontaneous delivery at term with retained fetal membranes (n=12). The enzyme
      activity was measured spectrophotometrically and expressed in nanokatals (nkat)
      per protein content. The activity increased towards parturition and was
      significantly higher in maternal than in fetal part of placenta in all groups
      examined. The significantly higher values in retained than in not retained
      placental tissues were observed in the samples examined. The present results
      indicate that the disturbances in 9-KPR activity in bovine retained placenta
      exist but their reasons still require further experiments.

PMID- 12054912
TI  - Effect of fatty acids on estradiol and testosterone binding to whole DU-145
      prostate cells.
AB  - Cancer of the prostate is one of the leading causes of cancer related deaths in
      men. An important role in the development of prostate cancer is played by
      androgens and androgen ablation is therefore currently used in cancer treatment.
      In the past, estrogens were widely used in treatment of prostate cancer, but
      there are indications that estrogens could also be involved in carcinogenesis.
      Lately, much research has been done on the modulation of the binding of steroid
      hormones to their receptors by polyunsaturated fatty acids (PUFAs), which could
      interfere with the steroid hormone's message. Therefore, the aim of this study
      was to determine in whole DU-145 human prostate cells the effect of EFAs and
      their metabolites on the binding and affinity of the estrogen receptor (ER) and
      androgen receptor (AR) to estradiol (E(2)) and testosterone (T), respectively.
      Fatty acids were dissolved in ethanol and added to the cell culture in a final
      ethanol concentration of 0.2% on the fourth day of incubation. The results showed
      that the PUFAs under investigation inhibited the AR's capacity, in contrast to
      the ER's capacity which was stimulated. However, the dissociation constants
      (K(d)) of the AR and ER complexes in the presence of the PUFAs, were as follows.
      Except for eicosapentaenoic acid (EPA) which decreased the AR dissociation
      constant and EPA and alpha-linolenic acid (ALA) which increased the ER
      dissociation constant, the remaining FAs had no significant effect on the K(d)
      values of both the AR and ER complexes. According to these priliminary results it
      is postulated that men should benefit with a diet rich in certain essential
      polyunsaturated fatty acids although its function remains to be clarified.

PMID- 12054913
TI  - Interleukin (IL)-17 enhances prostaglandin F(2 alpha)-stimulated IL-6 synthesis
      in osteoblasts.
AB  - We previously showed that prostaglandin F(2alpha) (PGF(2alpha)) and endothelin-1
      (ET-1) induce interleukin (IL)-6 through the activation of protein kinase C
      dependent p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3
      E1 cells. It has recently been reported that tumor necrosis factor-alpha-induced
      IL-6 synthesis is amplified by IL-17 in these cells. In the present study, we
      investigated the effect of IL-17 on the IL-6 synthesis stimulated by PGF(2alpha)
      in MC3T3-E1 cells. IL-17 significantly enhanced the PGF(2alpha)-induced IL-6
      synthesis in a dose-dependent manner in the range between 0.1 and 10 ng/ml. IL-17
      also enhanced the IL-6 synthesis stimulated by 12- O -tetradecanoylphorbol-13
      acetate, a direct activator of protein kinase C. In addition, IL-17 amplified the
      IL-6 synthesis induced by ET-1. However, IL-17 hardly affected the
      phosphorylation of p44/p42 MAP kinase induced by PGF(2alpha) or ET-1. These
      results strongly suggest that IL-17 enhances the IL-6 synthesis stimulated by
      PGF(2alpha) as well as ET-1 in osteoblasts, and that the effect is exerted at a
      point downstream from p44/p42 MAP kinase.

PMID- 12054914
TI  - Effects of n-3 polyunsaturated fatty acids on dermatitis in NC/Nga mice.
AB  - The administration of n-3 polyunsaturated fatty acids (PUFAs) is known to be
      effective against allergic diseases by suppressing the production of eicosanoids
      derived from arachidonic acid. To investigate the mechanisms and efficacy of n-3
      PUFA treatment in patients with atopic dermatitis (AD), we administered four
      different formulas of alpha-linolenic acid for 6 weeks in an AD model using
      NC/Nga mice. According to the doses of alpha-linolenic acid given, the levels of
      alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid in the red
      blood cell membranes increased while the levels of linoleic acid and arachidonic
      acid decreased. However, there was no significant difference among the four dose
      groups in clinical skin severity score, histopathological findings of skin
      lesions, or levels of total plasma IgE. Moreover, there was no significant
      difference in the production of leukotriene B(4) and Leukotriene C(4) from skin
      lesions after stimulation with A23187 among the groups, although the production
      of prostaglandin E(2) (PGE(2)) was significantly reduced and skin blood flow in
      the ear was significantly higher in the group given the highest dose of alpha
      linolenic acid. Our results suggest that the administration of alpha-linolenic
      acid can change the fatty acid composition, PGE(2) production, and skin blood
      flow but may not prevent the development of dermatitis in NC/Nga mice.

PMID- 12054915
TI  - Urinary excretion of 8-iso-PGF(2 alpha) in three patients during sepsis, recovery
      and state of health.
AB  - Sepsis is known to be associated with oxidative stress. Novel markers of
      oxidative stress are now believed to be F2-isoprostanes which are produced in
      situ in phospholipids and subsequently released into circulation and excreted in
      the urine. This study, therefore, sought to investigate whether the excretion of
      the isoprostane, 8-iso-PGF(2 alpha), is elevated during sepsis. The excretion of
      8-iso-PGF(2 alpha), in the 24 h urine of three patients was studied in the septic
      stage, during mobilisation and in the state of health by a radioimmunological
      method. Extrapolating the urinary excretion of 8-iso-PGF(2 alpha) over time
      showed an insignificant variation in the excretion values during 24 h. The amount
      of mean 24 h urinary 8-iso-PGF(2 alpha) was about similar in the septic stage and
      in the state of health but increased remarkably during mobilisation in two of the
      patients. We suggest that mobilisation of septic patients can be associated with
      an increase of oxidative stress which may stem from an increase in oxygen
      consumption and/or from a depletion of antioxidants leading to the enhanced
      formation of free radicals.

PMID- 12054916
TI  - Increased cytosol Ca(2+) and type 1 programmed cell death in Bcl-2-positive U937
      but not in Bcl-2-negative PC-3 and Panc-1 cells induced by the 5-lipoxygenase
      inhibitor MK 886.
AB  - MK 886, an arachidonic acid-related analog which inhibits the enzyme, 5
      lipoxygenase by an indirect mechanism involving the 5-lipoxygenase activating
      protein, rapidly increased U937 cytosol Ca(2+), much of which localized around
      the cell nuclei. Five-lipoxygenase activity was not directly involved since the
      direct redox-dependent 5-LPOx inhibitor, SC-41661A did not increase Ca(2+). U937
      cells subsequently undergo classic type 1 programmed cell death. At least
      initially the ionized calcium originates from internal stores. Coincident with
      the rise in U937 ionized calcium, MK 886 rapidly increased reactive oxygen
      species and reduced mitochondrial membrane potential, as judged by several
      fluorescent probes. The Ca(2+) response of myeloid leukemia-derived HL-60 cells
      to MK 886 was similar and both cell lines express Bcl-2 protein. Bcl-2-negative
      Panc-1 and PC-3 cells did not respond to MK 886 with a Ca(2+) signal but did
      develop oxidative stress and a decline in mitochondrial membrane potential; these
      events are thought to contribute to the inhibition of cell proliferation and
      induction of a type 2 PCD. In addition to its marked inhibition of Bcl-2 mRNA
      synthesis, an interesting hypothesis is that MK 886, serving as a low molecular
      weight ligand, either by direct or indirect inhibition of U937 Bcl-2 protein
      function, possibly related to an ion channel activity, alters the distribution of
      intracellular, possibly nuclear Ca(2+), thereby promoting the development of type
      1 programmed cell death.

PMID- 12054917
TI  - Antithrombotic effect of onion in streptozotocin-induced diabetic rat.
AB  - In the present study, we investigated whether onion has antithrombotic effect in
      streptozotocin (STZ)-induced diabetic rats. In diabetic rats, serum thromboxane
      B(2) (TXB(2)) level was elevated compared to that in normal, and this elevation
      in diabetes was significantly inhibited by treatment with onion (0.5 g/ml/kg/day,
      i.p.) for 4 weeks. In normal rats, the serum TXB(2) level remained unaltered
      after the treatment with onion. To investigate in vitro effect of onion, we
      examined its effect on TXB(2) formation, platelet aggregation and arachidonic
      acid (AA)-release in platelets from diabetic and normal rats. Onion showed a
      significant inhibitory effect on collagen- or AA-induced TXB(2) formation with
      greater potency in diabetic platelets than in normal. Similarly, more potent
      inhibitory effects of onion in diabetes were observed in collagen- or AA-induced
      platelet aggregation and collagen-induced AA release response. In conclusion,
      these results suggest that onion can produce more beneficial antithrombotic
      effect in diabetes.

PMID- 12054918
TI  - Studying mitochondria of animal cells.

PMID- 12054919
TI  - Isolation of biogenetically competent mitochondria from mammalian tissues and
      cultured cells.
AB  - This article describes a quick basic method adapted for the purification of
      mammalian mitochondria from different sources. The organelles obtained using this
      protocol are suitable for the investigation of biogenetic activities such as
      enzyme activity, mtDNA, mtRNA, mitochondrial protein synthesis, and mitochondrial
      tRNA aminoacylation. In addition, these mitochondria are capable of efficient
      protein import and the investigation of mtDNA/protein interactions by DNA
      footprinting is also possible.

PMID- 12054920
TI  - Protein import and processing reconstituted with isolated rat liver mitochondria
      and recombinant mitochondrial processing peptidase.
AB  - Most mitochondrial proteins are synthesized in the cytoplasm as larger precursors
      carrying N-terminal matrix-targeting presequences, and are subsequently
      transported to the mitochondria. The presequence mediates the interaction between
      the precursor polypeptide and components of the mitochondrial protein import
      machinery, a complex apparatus that is responsible for translocation of the
      precursor across the two mitochondrial membranes. Once the precursor has reached
      the mitochondrial matrix, the presequence is removed by the general mitochondrial
      processing peptidase (MPP). Some precursors undergo additional processing steps
      carried out by specialized processing peptidases. For most mitochondrial
      proteins, however, cleavage by MPP is the step that precedes folding and assembly
      into the native form. We describe methods to isolate import-competent
      mitochondria from rat liver and to perform import reactions with precursor
      proteins synthesized in vitro by coupled transcription-translation. We also
      describe methods to perform in vitro processing reactions of mitochondrial
      precursors by recombinant MPP and to identify the cleavage sites used by this
      enzyme.

PMID- 12054921
TI  - In vivo and in organello assessment of OXPHOS activities.
AB  - Mitochondrial OXPHOS defects are responsible for a large group of human diseases
      and have been associated with degenerative disorders and aging. The accurate in
      vivo and in organello biochemical assessment of the OXPHOS system is necessary
      for the diagnosis and investigation of such conditions. Here I describe a set of
      accurate polarographic and spectrophotometric assays that use relatively small
      amounts of biological material (cells or isolated mitochondria) and discuss the
      biochemical parameters appropriate for discriminating partial OXPHOS defects.

PMID- 12054922
TI  - Measurements of ATP in mammalian cells.
AB  - Levels of phosphorylated adenosine nucleotides, including the universal energy
      carrier adenosine 5(')-triphosphate (ATP) and its metabolites adenosine 5(')
      diphosphate (ADP) and adenosine 5(')-monophosphate (AMP), define the energy state
      in living cells and are dependent mainly on mitochondrial function. In this
      article, we describe a method based on the luciferase-luciferin system used to
      measure mitochondrial ATP synthesis continuously in permeabilized mammalian cells
      and mitochondria isolated from animal tissues. We also describe a technique that
      uses the expression of recombinant targeted luciferase to report ATP content in
      different cell compartments. Finally, we describe an HPLC-based method for
      accurate measurement of ATP, ADP, and AMP in cultured cells and animal tissues.

PMID- 12054923
TI  - Blue Native electrophoresis to study mitochondrial and other protein complexes.
AB  - The biogenesis and maintenance of mitochondria relies on a sizable number of
      proteins. Many of these proteins are organized into complexes, which are located
      in the mitochondrial inner membrane. Blue Native polyacrylamide gel
      electrophoresis (BN-PAGE) is a method for the isolation of intact protein
      complexes. Although it was initially used to study mitochondrial respiratory
      chain enzymes, it can also be applied to other protein complexes. The use of BN
      PAGE has increased exponentially over the past few years and new applications
      have been developed. Here we review how to set up the basic system and outline
      modifications that can be applied to address specific research questions.
      Increasing the upper mass limit of complexes that can be separated by BN-PAGE can
      be achieved by using agarose instead of acrylamide. BN-PAGE can also be used to
      study assembly of mitochondrial protein complexes. Other applications include in
      gel measurements of enzyme activity by histochemical staining and preparative
      native electrophoresis to isolate a protein complex. Finally, new ways of
      identifying protein spots in Blue Native gels using mass spectrometry are briefly
      discussed.

PMID- 12054924
TI  - Measuring mitochondrial reactive oxygen species.
AB  - This article examines recent methods for measuring reactive oxygen species
      produced in isolated mitochondria and within live cells, with particular emphasis
      on the detection of hydrogen peroxide. Protocols for reliable measurements of
      mitochondrial hydrogen peroxide are presented, while the advantages and pitfalls
      of these and other methods are discussed. New developments in the detection of
      lipid peroxidation are outlined. Advice is also provided to aid the
      interpretation of cellular data with respect to the contribution of oxygen
      radical production by different components of the mitochondrial respiratory
      chain.

PMID- 12054925
TI  - Analyzing mitochondrial changes during apoptosis.
AB  - Mitochondria play a central role in programmed cell death through the release of
      cytochrome c and other proapoptotic factors. Fluorescence microscopy is used to
      visualize cytochrome c translocation and loss of mitochondrial membrane
      potential. Flow cytometry can also be used to measure mitochondrial membrane
      potential. Cytochrome c content in cytosol and mitochondria can be determined by
      immunoblotting after subcellular fractionation or selective permeabilization with
      digitonin. Isolated mitochondria can be used to study the mechanism of cytochrome
      c release. This article summarizes some of the more widely used methods to assess
      mitochondrial alterations in apoptosis.

PMID- 12054926
TI  - Production of transmitochondrial mice.
AB  - With the advancement of various gene transfer technologies, the establishment of
      mitochondria transfer as a viable technique to genetically engineer mouse models
      paradoxically lagged behind other genetic technologies. The lack of demonstrable
      recombination in mtDNA necessitates different approaches to conventional
      transgenesis-based techniques. Initially, heteroplasmic mice were created to
      explore disease pathogenesis and mitochondrial dynamics in an in vivo system.
      Ultimately, transmitochondrial mouse models will be used to explore the role of
      the mitochondrial genome in human disease processes and in the development of
      novel human gene therapies. Here, we describe methodology to produce
      transmitochondrial mice (both homoplasmic and heteroplasmic models) harboring
      foreign mitochondrial genomes, using both embryo microinjection and embryonic
      stem (ES) cell-based approaches. Specific modeling and the procedures for
      mitochondrial transfer will be of considerable importance toward our
      understanding of discrete mitochondrial mutations, as well as lead to the
      development of novel strategies and therapies for human diseases influenced by
      mitochondrial DNA mutations.

PMID- 12054927
TI  - Production of mitochondrial DNA transgenic mice using zygotes.
AB  - Several animal models of human disease, which have been developed by random or
      targeted modifications of genomic DNA sequences, have furthered our understanding
      of pathogenesis and the development of therapeutics. However, these models have
      not facilitated studies on mitochondrial diseases, since modifications to
      mitochondrial DNA (mtDNA) sequences are not possible using current recombination
      techniques. Consequently, information on human mitochondrial diseases is
      relatively sparse, and issues related to mitochondrial pathogenesis and
      inheritance remain unresolved. Recently, we reported the development of a new
      technique to generate mice carrying mutant mtDNA from a mouse cell line. In this
      report, we describe our techniques in detail, with emphasis on the preparation of
      donor cytoplasts and the micromanipulative procedures for electrofusion of
      cytoplasts and recipient zygotes. These steps are critically important for the
      successful introduction of exogenous mtDNA into embryos, and thereby into
      animals, so that the mutant mtDNA is efficiently propagated in subsequent
      generations.

PMID- 12054928
TI  - Noninvasive, in vivo approaches to evaluating behavior and exercise physiology in
      mouse models of mitochondrial disease.
AB  - Mitochondrial diseases are a clinically heterogeneous group of disorders related
      to dysfunction of various components of oxidative metabolism. Common
      manifestations of these diseases include encephalopathy, skeletal myopathy, and
      cardiomyopathy, but essentially any tissue can be affected. To understand better
      the pathogenesis of mitochondrial disease and to potentially evaluate novel
      therapies, several mouse models have been reported in the literature over the
      past few years. In assessing genetically altered mice as potential models of
      human mitochondrial disease, careful behavioral and physiologic analyses are
      essential components of the overall phenotypic characterization. Noninvasive, in
      vivo approaches are useful because they assess end-organ and multiorgan function
      in a whole-organism context, as well as permit serial measurements of individual
      animals over time. This review presents various behavioral and exercise
      physiology protocols that can be used for the evaluation of potential mouse
      models of human mitochondrial disorders.

PMID- 12054929
TI  - Importance of specific hydrogen-bond donor-acceptor interactions for the key
      carbocycle-forming reaction catalyzed by 2-deoxy-scyllo-inosose synthase in the
      biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics.
AB  - A crucial enzyme in the biosynthesis of the 2-deoxystreptamine aglycon of
      clinically important aminocyclitol antibiotics is 2-deoxy-scyllo-inosose synthase
      (DOIS), which converts ubiquitous D-glucose 6-phosphate (G-6-P) into the specific
      carbocycle 2-deoxy-scyllo-inosose. Among all the oxygenated carbons of the
      substrate, C-1, -4, -5, and -6 are directly involved in the chemical
      transformation. To get insight into the roles of C-2 and C-3 hydroxy groups, 2
      deoxy-2-fluoro-, 3-deoxy-3-fluoro-, 2-amino-2-deoxy-, and 3-amino-3-deoxy-D
      glucose 6-phosphates (2-F-G-6-P, 3-F-G-6-P, 2-NH(2)-G-6-P, and 3-NH(2)-G-6-P,
      respectively) were subjected to the DOIS reaction as probe, since a fluorine
      substituent generally acts as a hydrogen-bond acceptor, and an ammonium
      functionality derived physiologically from an amino group as a hydrogen-bond
      donor. Among those tested, 2-F-G-6-P and 3-NH(2)-G-6-P were used as substrates by
      DOIS and were converted into the corresponding deoxyfluoro- and aminodeoxy-scyllo
      inososes, respectively. In contrast, 3-F-G-6-P and 2-NH(2)-G-6-P were inactive in
      the cyclization reaction. Clearly, DOIS recognizes the G-6-P substrate through
      specific hydrogen-bonding interactions, i.e., through a hydrogen-donating group
      for C-2 and an accepting group for C-3 of the substrate. Modeling of DOIS based
      on the structure of evolutionary-related dehydroquinate synthase is also
      described.

PMID- 12054930
TI  - Amino acid derived heterocycles: lewis acid catalyzed and radical cyclizations
      from peptide acetals.
AB  - Bicyclization of peptide acetals via nucleophilic attack of a phenyl group on an
      endocyclic acyliminium ion 4 was explored as a route to novel amino acid derived
      heterocycles and peptidomimetic scaffolds. In the presence of protic acid,
      bridged structures such as 6 are formed readily from phenylalanine derivatives,
      but the fused-ring analogues 5 could not be obtained in good yield. In contrast,
      radical cyclization of the bromophenyl dihydropyrazinone 7 provides an effective
      alternative for the synthesis of 5 (n = 0, 1, 2). Additional versatility in this
      process was demonstrated by efficient synthesis of a different fused ring system,
      represented by the antihelmintic praziquantel, 8.

PMID- 12054931
TI  - Do deviations from bond enthalpy additivity define the thermodynamic stabilities
      of diradicals?
AB  - Deviations from bond enthalpy additivity (DeltaBEA) are frequently used to assess
      the thermodyamic stabilities of diradicals. (U)B3LYP/6-31G calculations have been
      performed in order to determine how well DeltaBEA values actually do reflect the
      thermodynamic stabilities of the triplet states of diradicals in which one or
      both nonbonding electrons occupy a delocalized pi orbital. The calculations find
      that different pathways for forming sigma,pi-diradicals, such as alpha,2- and
      alpha,4-dehydrotoluene (4 and 6), give DeltaBEA values that differ by ca. 1
      kcal/mol. The path dependency of the DeltaBEA values is computed to be one order
      of magnitude larger for non-Kekule hydrocarbon diradicals, such as m
      benzoquinodimethane (12) and 1,3-dimethylenecyclobutane-2,4-diyl (15), than for
      sigma,pi-diradicals. Since the DeltaBEA values for forming 4, 6, 12, and 15 are
      all path dependent, we conclude that DeltaBEA values for diradicals with one or
      two delocalized, nonbonding pi electrons do not, in general, uniquely define the
      thermodynamic stabilities of the diradicals. Hence, DeltaBEA values should not be
      used for this purpose, especially for non-Kekule hydrocarbon diradicals.

PMID- 12054933
TI  - A method for easily determining coupling constant values: an addendum to "A
      practical guide to first-order multiplet analysis in 1H NMR spectroscopy".
AB  - A systematic procedure to decipher first-order 1H NMR multiplets is described.
      This method is a very practical tool for extracting coupling constant values. It
      requires only that one (a) learn to identify each of the 2n (n = number of spin
      1/2 nuclei to which the proton is coupled) "units of intensity" of a multiplet
      and (b) then apply a clearly delineated sequence of iterative steps that allows
      the J's to be assigned in order (from smallest to largest). The approach is even
      easier to use than one described previously (J. Org. Chem. 1994, 59, 4096-4103).

PMID- 12054934
TI  - Homochiral 4-azalysine building blocks: syntheses and applications in solid-phase
      chemistry.
AB  - Anomalous amino acids not only play central roles as mimics of natural amino
      acids but also offer opportunities as unique building blocks for combinatorial
      chemistry. This paper describes the chiral syntheses and solid-phase applications
      of a versatile atypical amino acid, 4-azalysine (2,6-diamino-4-azahexanoic acid)
      1. The syntheses of differentially protected 4-azalysine derivatives 28a-e have
      been developed by two efficient and inexpensive routes that start either from
      Garner's aldehyde 16 or the chiron (S)-N(alpha)-Cbz-2,3-diaminopropionic acid 23.
      Both approaches employ the convergent modular concept and exploit reductive
      amination of aldehydes with amines as the key step for the fusion of the two
      segments. In the first route, the overall process inverts the chirality of the
      starting material, L-serine, and thus provides an excellent route to the
      unnatural D-isomers. The alternative route starting from L-asparagine provides a
      shorter and high-yielding route to orthogonally protected 4-azalysine
      derivatives. The corresponding N(2)-Fmoc-4-azalysines 31a-e, readily derived from
      the key intermediate 27, are compatible with the Fmoc-based solid-phase peptide
      synthesis (SPPS) and solid-phase organic chemistry (SPOC) protocols. Furthermore,
      the utility and versatility of another key structure, tris-Boc-4-azalysine 2 in
      the engineering of novel high-loading dendrimeric polystyrene resins 33 and 36,
      have been demonstrated. Following derivatization with the Rink amide linker 34,
      the stability and robustness of these resin-bound dendrimers 35 and 37 in the
      synthesis of small molecules using a range of reaction conditions (e.g.,
      Mitsunobu and Suzuki reactions) have been effectively illustrated.

PMID- 12054932
TI  - Oligodeoxyribonucleotide analogues with bridging dimethylene sulfide, sulfoxide,
      and sulfone groups. Toward a second-generation model of nucleic acid structure.
AB  - Short DNA analogues with bridging dimethylene sulfide, sulfoxide, and sulfone
      groups replacing the phosphate diesters (S-DNAs) were synthesized from building
      blocks prepared via two routes, both starting from D-glucose. Building blocks for
      RNA analogues were prepared by stereoselective introduction of nucleobase into a
      2'-acylated ribose analogue. The ribose analogues were converted to deoxyribose
      analogues by replacement of a 3''-OH group by a thioacetyl unit, followed by
      photolytic deoxygenation or radical-based 2'-deoxygenation. DNA analogues joined
      via CH(2)(-)S-CH(2) units were prepared by S(N)2 displacement of a 6'-mesyl group
      on one building block using a thiolate nucleophile of another. 4,4'
      Dimethoxytrityl protection and deprotection schemes were established for both the
      thiol and hydroxyl groups. The corresponding sulfoxide DNA analogues were
      obtained by oxidation with hydrogen peroxide. Sulfone DNA analogues were obtained
      by oxidation of the sulfide DNA with persulfate or hydrogen peroxide in the
      presence of a titanium silicate catalyst. The physical properties of several
      representative oligonucleotide analogues were examined, and interpreted in light
      of a "second-generation" model for DNA strand-strand recognition, a model that
      emphasizes the role of the polyanionic backbone in diminishing unwanted
      tendencies of highly functionalized molecules to form "structure" in solution.
      Even short sulfide-linked DNA analogues displayed association properties
      different from those displayed by standard DNA molecules. Complex formation
      observed with sulfide-linked tetramers by HPLC study in different solvents
      suggested that the complex is formed using hydrogen bonding. Sulfone-linked
      dinucleotides display Watson-Crick behavior; the tetramer, however, displayed
      self-structure. Self-structure and self-aggregation become more prominent as the
      length of the oligonucleotide analogues increases. The tendency to self-aggregate
      can be decreased by adding a charged sulfonate group to the 3''-end of the DNA
      analogue. Features of the second-generation model are important for many areas of
      nucleic acid chemistry, from the design of nucleic acid therapeutic agents to the
      search for life on other planets.

PMID- 12054935
TI  - Mono- and bisadducts from the addition of thianthrene cation radical salts to
      cycloalkenes and alkenes.
AB  - Thianthrene cation radical salts, Th(*)(+) X(-)(X(-) = a, ClO(4)(-); b, PF(6)(-);
      c, SbF(6)(-)), add to cycloalkenes (C(5)-C(8)) in acetonitrile (MeCN) to form 1,2
      bis(5-thianthreniumyl)cycloalkane salts and 1,2-(5,10
      thianthreniumdiyl)cycloalkane salts, most of which have now been isolated and
      characterized. These are called bis- (3, 6, 9, 12) and monoadducts (4, 7, 10,
      13). The proportional amount of the monoadduct obtained in the initial stage of
      the reaction varied with the cycloalkene in the order C(6) << C(5) < C(7) <<
      C(8). Thus, the ratio bis:mono for C(5) and C(7) was, respectively, about 80/20
      and 50/50. In contrast, only about 5% of the C(6) monoadduct (7a) and none of
      7b,c was obtained, while for C(8) none of the bisadducts 12a-c was found.
      Bisadducts 3 and 9 lost thianthrene (Th) slowly in MeCN solution and changed into
      monoadducts 4 and 10. A comparable change from 6a into 7a was not observed. The
      monoadducts, themselves, lost a proton slowly in dry MeCN and opened into 1-(5
      thianthreniumyl)cycloalkenes (5, 8, 11, 14). With 3 and 9, particularly, it was
      possible to follow with NMR spectroscopy the succession of changes, for example,
      3 to 4 to 5. The opening of a monoadduct was made faster by adding a small amount
      of water to the solution. The bisadducts of 4-methylcyclohexene (15a) and 1,5
      cyclooctadiene (17a) were isolated and characterized. Although a small amount of
      monodduct (16a) of 4-methylcyclohexene was found with NMR spectroscopy, it could
      not be isolated. Bis- and monoadducts were obtained also in additions of Th(*)(+)
      ClO(4)(-) to acyclic alkenes, in relative amounts that, again, varied with the
      alkene. From cis-2-butene the dominant product was the bisadduct (18), while the
      monoaduct (19) was characterized with NMR spectroscopy but could not be isolated.
      In contrast, trans-3-hexene gave mainly the monoadduct (21), while the bis adduct
      (20) could not be isolated. With 4-methyl-cis-2-pentene, both bis- (22) and
      monoadduct (23) were isolated, the former being dominant. The conversion of 18
      into 19 was characterized with NMR spectroscopy. In all cycloalkene bisadducts,
      the configurational relationship of the two thianthrenium groups was trans, while
      in the monoadducts, the bonds to the single thianthrene dication were
      (necessarily) cis. In both bis- and monoadducts of acyclic alkenes, the
      configuration of the alkene was retained. The mechanisms of addition with
      retention of configuration, of conversion of a bis- into a monoadduct, and of
      opening of a monoadduct are discussed. Products were identified with a
      combination of NMR spectroscopy, X-ray crystallography, elemental analysis, and
      (for cycloalkene adducts) reaction with thiophenoxide ion.

PMID- 12054936
TI  - Synthesis and characterization of a new tetradentate ligand for Cu(II) metal
      ions.
AB  - The synthesis and characterization of a tailor-made ligand 1 is described. Self
      assembly of 1 on a GaAs surface was studied by FT-IR spectroscopy. The IR
      spectrum of the thin film points to the conclusion that the monolayer adsorbs to
      the surface via both carboxylates of the malonic acid derivative. The distinction
      between the possible binding modes is discussed.

PMID- 12054938
TI  - Tracing the allomerization pathways of chlorophylls by (18)O-labeling and mass
      spectrometry.
AB  - The Willstatter allomerization reaction of chlorophylls (Chl) has posed a
      difficult problem in Chl and photosynthesis research over the past 90 years.
      Here, we present strong additional evidence, based on (18)O-labeling and mass
      spectrometry, for the previously published free-radical allomerization (FRA)
      mechanism (Hynninen, Z. Naturforsch. 1981, 36b, 1010-1016). This mechanism is
      also complemented now by describing two alternative pathways for the formation of
      13(2)(S/R)-hydroxy-Chl a. The results from the (18,18)O(2)-experiments suggest
      that the predominant route for the formation of the 13(2)(S/R)-hydroxy-Chl a
      under essentially anhydrous conditions (anhydrous Chl and thoroughly dried
      methanol) is the homolytic cleavage of the C-13(2)-hydroperoxide intermediate.
      However, if Chl dihydrate and undried methanol are used in the reaction mixture,
      the direct route from the Chl C-13(2) radical to 13(2)(S/R)-hydroxy-Chl a can be
      predicted to become significant. The results from the (18,18)O(2)-allomerization
      experiments described in this paper also verified that the 13(2)(S/R)-methoxy
      lactone derivatives and the 15-glyoxylic acid derivative of Chl a incorporated
      each a single (18)O-atom, whereas 13(2)(R/S)-methoxy-Chl a remained unlabeled.
      Consequently, these allomers are formed via the pathways previously suggested in
      the original FRA mechanism. The possible factors contributing to the control of
      the allomerization reactions are considered. Finally, the relationship between
      the allomerization reactions of Chl a and those of Chl b and BChl a is briefly
      discussed.

PMID- 12054937
TI  - Synthesis of chiral pyrrolo[1,2-c]thiazoles via intramolecular dipolar
      cycloaddition of munchnones: an interesting rearrangement to pyrrolo[1,2
      c]thiazines.
AB  - Intramolecular dipolar cycloaddition of bicyclic munchnones, 5H,7H-thiazolo[3,4
      c]oxazol-4-ium-1-olates, derived from cyclodehydration of 2-substituted-N
      acylthiazolidine-4-carboxylic acids are reported. A range of new pyrrolo[1,2
      c]thiazole derivatives (7, 14, 15, 20, 23, and 26) were obtained as single
      enantiomers from 2-phenylthiazolidines, 2-benzoylthiazolidines, and 2
      methylthiazolidine-4-carboxylates. Pyrrolo[1,2-c][1,4]thiazine derivative 27 was
      also obtained from pyrrolo[1,2-c]thiazole derivative 26. The structures of methyl
      (2R,4R)-2-(p-methoxybenzoyl)thiazolidine-4-carboxylate (17a), methyl (2R,4R)-2-(p
      methoxybenzoyl)-N-(prop-2-ynyloxyacetyl)thiazolidine- 4-carboxylate (18), and 3
      oxo-4-phenyl-3,4,6,8-tetrahydro-1H-furo[3',4':2,3]pyrrolo[1,2-c][1,4]thiazine
      (27) were determined by X-ray crystallography. Chirooptical studies of the
      pyrrolo[1,2-c]thiazoles were done by confirming the absolute configuration at the
      chiral center C-3.

PMID- 12054939
TI  - Design, synthesis, and evaluation of matrix metalloprotease inhibitors bearing
      cyclopropane-derived peptidomimetics as P1' and P2' replacements.
AB  - We have previously used trisubstituted cyclopropanes as peptide replacements to
      induce conformational constraints in known pseudopeptide inhibitors of a number
      of important enzymes. Cyclopropane-derived peptide mimics are novel in that they
      are among the few replacements that locally orient the peptide backbone and the
      amino acid side chain in a predefined manner. Although these dipeptide isosteres
      have been employed to orient amino acid side chains mimicking the gauche(-)
      conformation of chi(1)-space, their ability to project the side chains into an
      anti orientation has not been evaluated. As a first step toward this goal, the
      conformationally constrained pseudopeptides 8 and 10 and their corresponding
      flexible analogues 9 and 11 were prepared and tested as inhibitors of matrix
      metalloproteinases (MMPs). These compounds are analogues of 4 and 5, which were
      known to be potent MMP inhibitors. The anti orientations of the isopropyl side
      chain in 8 and the aromatic ring in 10 relative to the peptide backbone
      substituents on the cyclopropane were predicted to correspond to the known
      orientations of the P1' and P2' side chains of 5 when bound to MMPs. Hence, 8 and
      10 were designed explicitly to probe topological features of the S1' or the S2'
      binding pockets of the MMPs. They were also designed to explore the importance of
      the P1'-P2' amide group, which is known to form highly conserved hydrogen bonds
      in several MMP-inhibitor complexes, and the viability of introducing a retro
      amide linkage between P2' and P3'. Pseudopeptides 8 and 9 were found to be weak
      competitive inhibitors of a series of MMPs. Any entropically favorable
      conformational constraints that were induced by the cyclopropane in 8 were thus
      overwhelmed by the loss of the hydrogen bonding capability associated with the
      P1'-P2' amide group. On the other hand, compounds 10 and 11, which contain a P2'
      P3' retro amide group, were modest competitive inhibitors of a series of MMPs.
      The results obtained for 10 and 11 suggest that there may be a loss of hydrogen
      bonding capability associated with introducing the P2'-P3' retro amide group.
      However, because the conformationally constrained pseudopeptide 10 was
      significantly more potent than its flexible analogue 11, trisubstituted
      cyclopropanes related to 3 may serve as useful rigid dipeptide replacements in
      some biologically active pseudopeptides.

PMID- 12054941
TI  - A new, facile synthesis of 1,4,7,10-tetraazacyclododecane: cyclen.
AB  - This report outlines a new and efficient synthesis of cyclen (1,4,7,10
      tetraazacyclododecane, 1) utilizing bis-imidazoline, 6 (1,1'-ethylenedi-2
      imidazoline), with 1,2-dibromoethane. General conditions were developed, allowing
      for the simple, three-step synthesis of 1 at the multigram scale with an isolated
      overall yield approaching 65%. The cyclization of 6 produced by the condensation
      of triethylene tetraamine (TETA) with N,N-dimethylformamide dimethyl acetal, gave
      the twelve-membered, imidazolinium, cyclized intermediate bromide salt, 7
      (2,3,4,5,6,7,8,8c-octahydro-1H-4a,6a,8a-triaza-2a
      azoniacyclopent[fg]acenaphthylene), which hydrolyzed to 1 with the use of hot,
      aqueous caustic. Hydrolysis of 7 under milder conditions formed the 1,4,7,10
      tetraazabicyclo[8.2.1]tridecan-13-one (20). Mechanistically, the formation of 7
      may be rationalized as involving a diaminocarbene that undergoes an
      intramolecular carbon-hydrogen insertion.

PMID- 12054940
TI  - Asymmetric synthesis of 4'-ethoxy-2',3'-didehydro-2',3'-dideoxynucleosides by
      palladium-catalyzed kinetic discrimination between the corresponding
      diastereoisomeric lactol acetates.
AB  - 4'-Substituted nucleoside analogues have been synthesized using palladium
      catalyzed asymmetric allylic amination conditions. A kinetic discrimination
      between the diastereomeric lactol acetates (3) produced the desired aminated
      products (6a-d) and recovered acetate (alpha-3) in high yields and <97:3
      diastereoselectivity. Epimerization of the recovered lactol acetate (alpha-3)
      produced a 60:40 alpha/beta mixture of (3), which could be resubjected, in
      principle, to the palladium-catalyzed asymmetric allylic amination conditions.

PMID- 12054942
TI  - Catalytic oxidative carbonylation of primary and secondary diamines to cyclic
      ureas. Optimization and substituent studies.
AB  - W(CO)(6)-catalyzed oxidative carbonylation of 1,3-propanediamine to the
      corresponding urea has been examined under a variety of conditions. Following
      optimization, the Thorpe-Ingold effect on ring closure was studied using 2,2
      dialkyl-1,3-propanediamines. For the 2,2-dimethyl- and 2,2-dibutyl-1,3
      propanediamines, the yields were increased significantly as compared to that of
      the unsubstituted case. The eight-membered cyclic urea 5-butyl-5-ethyl-1,3
      diazepan-2-one (5f) was formed in 38% yield, while only trace amounts of the
      cyclic urea were produced from the parent 1,5-pentanediamine. In a study of
      secondary diamines, yields from the carbonylation of N,N'-dialkyl-2,2-dimethyl
      1,3-propanediamines were lower than those obtained from the primary diamines. The
      main byproducts from secondary diamines were tetrahydropyrimidine derivatives
      formed from a competitive reaction of the substrate with the oxidant and base.

PMID- 12054943
TI  - Z-selective synthesis of alpha,beta-unsaturated amides with
      triphenylsilylacetamides.
AB  - With the purpose of developing a method of preparing Z-alpha,beta-unsaturated
      amides, the Peterson reaction of the (triphenylsilyl)acetamide Ph(3)SiCH(2)COX
      (1, X = NBn(2); 3, X = NMe(2)) with various aldehydes was examined. The reaction
      of aromatic aldehydes gave selectivities up to >97:3. It was found that the
      selectivity was a function of the electronic nature of the aromatic ring and
      higher Z selectivity was attained with electron-rich aldehydes. With aliphatic
      aldehydes selectivities up to 92:8 were achieved, and unlike with analogous
      phosphorus reagents, less sterically hindered aldehydes gave higher Z
      selectivity. Also, 3, which has a smaller amide group than 1, tended to give rise
      to higher selectivity. A comparison with the reaction of trimethylsilyl analogues
      revealed the significance of the phenyl substituents on the silyl group.

PMID- 12054944
TI  - Reactivities of methylenetriangulanes and spirocyclopropanated
      bicyclopropylidenes toward bromine. Relative stabilities of spirocyclopropanated
      versus methyl-substituted bromonium ions.
AB  - The bromine additions to methylenecyclopropane (1), bicyclopropylidene (2), and
      spirocyclopropanated methylenecyclopropanes and bicyclopropylidenes 3-6 in
      methanol at 25 degrees C proceed essentially with the same rate as those to the
      corresponding oligomethyl-substituted ethylenes. An increasing number of
      spiroannelated three-membered rings enhances the rate of bromination and
      stabilizes the intermediate cyclopropyl bromonium cations against ring opening in
      the course of bromine addition. Calculations at the B3LYP/6-311G(d,p) level show
      that unsymmetrical bromonium ions are the intermediates, and that they are
      stabilized by the spiroannelation with cyclopropane rings. The bromonium ion
      derived from 1 is less stable by 6.3 kcal mol-1 than that from isobutene. One or
      two spirocyclopropane rings as in 3 and 4 stabilize the corresponding bromonium
      ion by 9.6 and 16.4 kcal mol-1, respectively, while one or two alpha-cyclopropyl
      substituents as in ethenylcyclopropane (7) and 1,1-dicyclopropylethene (8)
      stabilize the corresponding bromonium ions by 13 and 29 kcal mol-1, respectively.
      The experimental bromination rates of all the studied alkenes correlate
      reasonably well (r2 = 0.93) with calculated relative energies of the
      corresponding bromonium ions. The correlation is even better within the series of
      methylenecyclopropanes 1, 3, and 4 (r2 = 0.974) and bicyclopropylidenes 2, 5, and
      6 (r2 = 0.999). The experimental bromination rates also correlate fairly well
      with the first ionization energies of the corresponding alkenes 1-12 (with r2 =
      0.963) and 13-19 (with r2 = 0.991). The calculated preferred nucleophilic attack
      of a water molecule at both the C1' and C1 atoms of representative bromonium ions
      conforms well to the experimentally observed product distribution.

PMID- 12054946
TI  - Synthesis of cyclic enol ethers from alkenyl-beta-dicarbonyl compounds.
AB  - In this work we describe the cyclofunctionalization of eleven differently
      substituted alkenyl-beta-dicarbonyl compounds, employing three electrophilic
      reagents, namely, iodine, p-methoxyphenyltellurium trichloride, and
      phenylselenenyl bromide. The reactions occur through the enolic form of the
      substrates, to afford the corresponding iodo-, telluro-, or selenocyclic enol
      ethers. Substrates bearing trisubstituted double bonds failed in reacting with
      the selenium and tellurium reagents. In general, beta-diketones reacted faster
      than beta-keto esters with the three studied electrophiles.

PMID- 12054945
TI  - Regio- and stereoselective ring openings of 3-Aza-2-oxabicyclo[2.2.1]hept-5-ene
      systems with copper catalyst-modified grignard reagents: application to the
      synthesis of an inhibitor of 5-lipoxygenase.
AB  - Treatment of acylnitroso hetero Diels-Alder cycloadducts 2 with organomagnesium
      reagents in the presence of a catalytic amount of copper induces ring opening to
      afford predominantly monocyclic anti-1,2-hydroxamic acids 12. Alkylmagnesium
      reagents were found to give superior regio- and stereoselectivities compared with
      vinyl and arylmagnesium reagents. This cycloadduct ring opening methodology was
      applied to the synthesis of a unique cyclopentenyl hydroxamic acid-based
      inhibitor of 5-lipoxygenase.

PMID- 12054947
TI  - Total synthesis of (+)-Brefeldin A.
AB  - The total synthesis of (+)-brefeldin A has been accomplished via 15 linear steps
      in a 7.9% overall yield from the known Weinreb amide 6. The key parts of this
      approach include the stereoselective construction of the cis-disubstituted
      hydroxycyclopentane skeleton and the direct introduction of the C1-C3 acrylate
      moiety using a new variant of a trans-vinylogous acyl anion equivalent.

PMID- 12054948
TI  - Involvement of triplet excited states and olefin radical cations in electron
      transfer cycloreversion of four-membered ring compounds photosensitized by
      (thia)pyrylium salts.
AB  - Cycloreversion of 1,2,3,4-tetraphenylcyclobutanes 1a,b and oxetane 2 is achieved
      using (thia)pyrylium salts as electron-transfer photosensitizers. Radical cation
      intermediates involved in the electron-transfer process have been detected using
      laser flash photolysis. The experimental results are consistent with the reaction
      taking place from the triplet excited state of the sensitizer.

PMID- 12054949
TI  - Solid-phase oligosaccharide and glycopeptide synthesis using glycosynthases.
AB  - Enzymatic approaches for the preparation of oligosaccharides are interesting
      alternatives to traditional chemical synthesis, the main advantage being the
      regio- and stereoselectivity offered without the need for protecting groups. The
      use of solid-phase techniques offers easy workup procedures and the prospect of
      automatability. Here, we report the first application of glycosynthases to solid
      phase oligosaccharide synthesis by use of the 51 kDa serine and glycine mutants
      of Agrobacterium sp. beta-glucosidase, Abg E358S and E358G. Acceptors were linked
      to PEGA resin through a backbone amide linker (BAL), and using these mutated
      enzymes, a galactose moiety was transferred from a donor sugar, alpha-D
      galactosyl fluoride, with high efficiency (>90%) together with excellent recovery
      of material. Furthermore, it was demonstrated that a resin-bound model
      glycopeptide was also an acceptor for the glycosynthase.

PMID- 12054950
TI  - Oligofuranosides containing conformationally restricted residues: synthesis and
      conformational analysis.
AB  - The synthesis of a panel of arabinofuranosyl oligosaccharide analogues (5-13) in
      which one ring is locked into either the E(3) or OE conformation is described.
      The E(3)-locked scaffolds 15 and 16 required for the synthesis of 5-10 were
      prepared in one step from known 1,5-anhydroalditols. A number of routes were
      explored for the preparation of the OE-locked monosaccharide derivative 17 needed
      for the preparation of 11-13. The successful synthesis of 17 was achieved in 17
      steps from D-arabinose. Subsequent analysis of 5-13 by 1H NMR spectroscopy
      demonstrated that the locked residue does not exert any detectable influence upon
      the conformers populated by adjacent conformationally unrestricted furanose
      rings.

PMID- 12054951
TI  - Catalytic asymmetric benzylic C-H activation by means of carbenoid-induced C-H
      insertions.
AB  - Tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-prolinate]dirhodium [Rh(2)(S-DOSP)(4)]
      catalyzed decomposition of methyl aryldiazoacetates in the presence of
      substituted ethylbenzenes results in benzylic C-H activation by means of a
      rhodium-carbenoid-induced C-H insertion. A Hammet study showed that positive
      charge buildup occurred on the benzylic carbon in the transition state of the C-H
      activation step. C-H activation of toluene and isopropylbenzene is possible, but
      a competing double cyclopropanation occurs with these substrates. The C-H
      activation is highly regioselective and enantioselective, and in certain cases,
      moderate diastereoselectivity is also possible.

PMID- 12054952
TI  - Modulation of the porphyrin inner proton exchange rates by the steric effects of
      bridge substitution.
AB  - The tautomeric equilibria and H-N proton transfer taking place in the
      nonsymmetrically substituted water-soluble 2-sulfonato-5,15-bis(4
      sulfonatophenyl)porphyrin (1) and in its 10-bromo-substituted derivative (2) were
      analyzed by NMR methods: 1H and 13C spectroscopies and heteronuclear multiple
      bond correlation (HMBC) and heteronuclear single quantum coherence (HSQC) 1H-13C
      and 1H-15N techniques. The existence of preferred pathways of H-N transfer was
      detected. The conclusions are rationalized by taking into account the effect
      partial meso-substitution exerts on the relative energies of the different cis
      tautomer intermediates involved in the tautomerism. These results underline the
      experimental consequences stemming from the nonequivalence in porphyrins between
      the 'tautomeric interconversion' and 'proton transfer' terms, when observed by
      NMR techniques, as a consequence of the existence of two pairs of degenerate
      tautomers and transformation pathways.

PMID- 12054953
TI  - Synthesis of furano[2,3-c]pyran-3-one and thieno[2,3-c]pyran-3-one derivatives
      through the coupling of 3-alkynyl-2-heteroaromatic carboxaldehydes with Fischer
      carbene complexes: total synthesis of a Baccharis-derived cadinene derivative.
AB  - The coupling of Fischer carbene complexes with 3-alkynyl-2-heteroaromatic
      carboxaldehyde derivatives has been examined. The reaction affords pyrones fused
      to furans or thiophenes in a single step. The compounds are stable enough for
      isolation. If the carbene complex features a remote alkene substituent, a
      subsequent Diels-Alder reaction can occur. This reaction has been used as the key
      step in the synthesis of a naturally occurring cadinene derivative.

PMID- 12054954
TI  - Linear total synthetic routes to beta-D-C-(1,6)-linked oligoglucoses and
      oligogalactoses up to pentaoses by iterative Wittig olefination assembly.
AB  - Two complementary routes, A and B, have been followed for the stepwise iterative
      assembly of beta-D-(1,6)-glucopyranose and galactopyranose residues through
      methylene bridges. In route A the building block was constituted by 2,3,4-tri-O
      benzyl-6-O-tert-butyldiphenylsilyl (O-TBDPS) beta-linked
      galactosylmethylenephosphorane, while in route B the building block was a beta
      linked formyl C-glycopyranoside with a similar orthogonal protection of hydroxy
      groups. In route A each cycle consisted of the reaction of the phosphorane
      building block with a sugar residue bearing a formyl group at the C-5 carbon atom
      (coupling) and transformation of the O-TBDPS-protected primary alcohol into the
      formyl group (arming). Accordingly, route A is defined as the aldehyde route. On
      the other hand, each cycle in route B involved the coupling of the sugar aldehyde
      building block with a substrate bearing a phosphorus ylide at C-6 and
      introduction of the phosphonium group in the arming step as a precursor of the
      ylide functionality. Accordingly, route B is defined as the ylide route. The
      efficiency of route A proved to be seriously hampered by the 1,2-elimination of
      BnOH under the basic reaction conditions of the Wittig olefination, giving rise
      to the formation of substantial amounts of enopyranose. On the other hand, the
      ylide route B proved to be more efficient since very good yields (70-93%) of the
      isolated Wittig products were obtained throughout four consecutive cycles.
      Individual olefins and polyolefins obtained by routes A and B using gluco and
      galacto substrates were reduced and debenzylated in one pot by H(2)/Pd(OH)(2) to
      give the corresponding beta-D-C-(1,6)-linked oligosaccharides up to the pentaose
      stage. The latter compounds were fully characterized by high-field NMR
      spectroscopy (500 MHz).

PMID- 12054955
TI  - Novel approach to the zaragozic acids. Enantioselective total synthesis of 6,7
      dideoxysqualestatin H5.
AB  - The total synthesis of 6,7-dideoxysqualestatin H5 (3) has been completed by a
      concise approach that features the stereoselective intramolecular vinylogous
      aldol reaction of the furoic ester 25a to give 30 or its trimethylsilyl ether
      derivative 34, which possess the requisite absolute stereochemistry at C(3)-C(5)
      of 3. Compound 34 was reduced to the saturated bislactone 39, and the C(1) side
      chain subunit 47 was introduced leading to a mixture of the hemiacetals 48 and
      the corresponding ketone 49. When this mixture was stirred with methanolic acid,
      transketalization occurred to give a mixture of 50 and the spirocyclic methyl
      acetals 51a,b. Oxidation of the primary alcohol group in 50 followed by
      saponification of the two remaining ester groups gave 3. The longest linear
      sequence in the synthesis commences with commercially available erythronolactone
      (26) and requires 17 chemical steps with only 10 isolated intermediates.

PMID- 12054956
TI  - Preparation of ferrocene-containing phosphinamine ligands possessing central and
      planar chirality and their application in palladium-catalyzed asymmetric allylic
      alkylation.
AB  - The preparation of [2-(S(p))-[(trans-(2R,5R)-2,5
      dialkylpyrrolidinyl)methyl]]ferrocenyldiphenyl phosphines, new
      ferrocenylphosphinamine ligands possessing one site of planar and two stereogenic
      centers, is described. trans-(2R,5R)-2,5-Dialkyl-1-(ferrocenylmethyl)pyrrolidines
      were diastereoselectively lithiated and quenched with chlorodiphenylphosphine.
      For the dimethyl ligand, chemical yields of up to 65% and des of up to 90% were
      obtained whereas the diethyl ligand afforded lower chemical yields (10%) and des
      of 78%. Diastereomerically pure material was obtained in both cases after a
      single recrystallization from ethanol. (S)-Planar chirality was confirmed by X
      ray crystallographic analysis of the dimethyl ligand. The palladium complexes of
      the new ligands were applied in the allylic alkylation of 1,3-diphenylprop-2-enyl
      acetate with reasonable chemical yields and moderate ees of up to 36% and 38%
      when dimethyl malonate and dimethyl methyl malonate were employed as
      nucleophiles, respectively. Importantly, it was found that the new ligands
      possessing the combination of planar and central chirality gave the opposite
      enantiomeric alkylation products compared to ligands which possess only the
      central chirality of the trans-2,5-dimethylpyrrolidinyl moiety. Solution NMR
      studies of the 1,3-diphenylallyl palladium complex of the dimethyl ligand
      revealed the presence of only the exo-configured allyl diastereomer.

PMID- 12054957
TI  - Synthetic procedure for various selenium-containing electron donors of the
      bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) type.
AB  - Six selenium variants of BEDT-TTF have been successfully synthesized by a newly
      developed synthetic method that involves a combination of two key reactions for
      the construction of two kinds of heterocyclic rings: the first is a one-pot
      formation of 1,3-dichalcogenole-2-chalcogenones from a common starting material,
      THP-protected 2-(ethynylthio)ethanol, leading to the inner five-membered rings,
      and the other is the annelation of the outer six-membered heterocyclic ring onto
      the inner ring by an intramolecular transalkylation reaction on a chalcogen atom.
      This method turned out to be widely applicable to the syntheses of the electron
      donors of bis(ethylenedithio)- and bis(ethyleneselenothio)-substituted types.
      However, synthetic attempts to form analogous donors of the bis(ethylenediseleno)
      substituted type from THP-protected 2-(ethynylseleno)ethanol were unsuccessful.
      This is attributable to the predominance of side-reactions via a seleniranium
      (episelenonium) salt over the desired six-membered ring formation by
      transalkylation via a seleninium salt.

PMID- 12054958
TI  - Time-resolved resonance Raman and density functional theory investigation of
      iodocyclopropanation and addition reactions with alkenes after ultraviolet
      photolysis of iodoform.
AB  - A time-resolved resonance Raman spectroscopic investigation is reported for the
      ultraviolet photolysis of CHI(3) in pure cyclohexane and mixed
      cyclohexane/cyclohexene solvents. The ICHI-I species is observed in pure
      cyclohexane solvent. Upon addition of cyclohexene, the ICHI-I species lifetime is
      reduced and new bands from an I(2):cyclohexene complex are observed. Density
      functional theory computations show that ICHI-I and CHI(2) species have similar
      barriers of reaction toward addition to the C=C of ethylene. The addition
      reaction of ICHI-I with ethylene results in formation of an iodocyclopropane and
      I(2) molecule while addition of.CHI(2) results in initial formation of a
      diiodopropyl radical intermediate. Ultraviolet photolysis of CHI(3) in the
      presence of cyclohexene is known to produce a reasonable yield of iodonorcarane
      product and some addition reaction products. We present a mechanism for the
      iodocyclopropanation reaction that is consistent with both experimental and
      theoretical characterization of reaction intermediates formed after ultraviolet
      photolysis of CHI(3). We briefly discuss the concentration dependence of the time
      resolved resonance Raman spectra and photochemistry in relation to the
      competition between the reaction of the ICHI-I and CHI(2) species with the C=C
      bond of olefins.

PMID- 12054959
TI  - Secondary deuterium kinetic isotope effects in irreversible additions of allyl
      reagents to benzaldehyde.
AB  - The competitive kinetics of additions of allyl to benzaldehyde-h and -d from
      allyltributyl tin, from diisopropyltartrylallyl boronate, and from allyl bromide
      and zinc dust in aqueous tetrahydrofuran have inverse secondary deuterium kinetic
      isotope effects, SDKIEs. These inverse SDKIEs are in contrast to the normal
      SDKIEs that were obtained with allyl lithium and allyl Grignard, suggesting rate
      determining single-electron transfer in these cases. By various MO calculations
      the transition state for addition of allyl boronate occurs with substantial B-O
      bond formation and little C-C bond formation. The magnitudes of the SDKIEs with
      the other two allylating reagents, when compared with reasonable equilibrium
      isotope effects for the addition, suggest transition states with substantial C-C
      bond formation.

PMID- 12054960
TI  - Incorporation of Ahc into model dipeptides as an inducer of a beta-turn with a
      distorted amide bond. Conformational analysis.
AB  - The proline residue of dipeptides Ser-Pro and Pro-Ser has been replaced by 7
      azabicyclo[2.2.1]heptane-1-carboxylic acid (Ahc), a conformationally restricted
      analogue of proline that is capable of mimicking distorted amides. The
      conformational analysis of the new peptides in the solid state revealed that the
      Ahc-Ser sequence displays a type I beta-turn, which includes a distorted amide
      bond. In contrast, the Ser-Ahc sequence exists in a nonfolded structure.

PMID- 12054961
TI  - The origins of noncovalent catalysis of intermolecular Diels-Alder reactions by
      cyclodextrins, self-assembling capsules, antibodies, and RNAses.
AB  - The catalysis of Diels-Alder reactions by noncovalent binding by synthetic,
      protein, and nucleic acid hosts has been surveyed and compared. These catalysts
      consist of binding cavities that form complexes containing both the diene and the
      dienophile; the cycloaddition reaction occurs in the cavity. The binding requires
      no formation of covalent bonds and is driven principally by the hydrophobic (or
      solvophobic) effect. A molecular mechanics and dynamics study of the cyclodextrin
      catalysis of a Diels-Alder reaction is used to exemplify and probe this form of
      catalysis. Detailed kinetic data is available for catalysis by antibodies, RNA,
      cyclodextrins, and Rebek's tennis ball capsules. Some of these catalysts
      stabilize the reactants more than the transition state and consequently will only
      have catalytic effect under conditions of low substrate-to-catalyst ratios. None
      of the hosts achieve significant specific binding of transition states that is
      the hallmark of enzyme catalysis.

PMID- 12054962
TI  - The power of visual imagery in synthesis planning. Stereocontrolled approaches to
      CGP-60536B, a potent renin inhibitor.
AB  - Two strategies were developed toward the stereocontrolled synthesis of 8-aryl-3
      hydroxy-4-amino-2,7-diisopropyloctanoic acids with predetermined stereogenic
      centers. This is a generic motif in a new class of potent inhibitors of the
      enzyme renin, exemplified by CGP-60536B. The synthesis relies on the utilization
      of L-pyroglutamic acid as chiron, and proceeds through the incorporation of
      required functionality by exploiting internal induction. One of the strategies
      shows the power of visual imagery in synthesis planning, akin to a Dali-like
      representation of objects that can be viewed in more than one way. Thus, the
      entire carbon skeleton of the target molecule is encompassed in a partially
      functionalized bicyclic indolizidinone precursor. In a second strategy, an
      intermediate common to the first approach is elaborated into an appended gamma
      lactone which is alkylated through enolate chemistry and ultimately transformed
      into the intended target compound. X-ray crystallography was used to corroborate
      the structures and stereochemistries of several intermediates.

PMID- 12054963
TI  - Studies on the synthesis of bafilomycin A(1): stereochemical aspects of the
      fragment assembly aldol reaction for construction of the C(13)-C25) segment.
AB  - Highly stereoselective syntheses of aldols 8a-c corresponding to the C(13)-C(25)
      segment of bafilomycin A(1) were developed by routes involving fragment assembly
      aldol reactions of chiral aldehyde 6a and the chiral methyl ketones 7. A remote
      chelation effect plays a critical role in determining the stereoselectivity of
      the key aldol coupling of 6a and the lithium enolate of 7b. The protecting group
      for C(23)-OH of the chiral aldehyde fragment also influences the selectivity of
      the lithium enolate aldol reaction. In contrast, the aldol reaction of 6a and the
      chlorotitanium enolates of 7a,c were much less sensitive to the nature of the
      C(15)-hydroxyl protecting group. Studies of the reactions of chiral aldehydes
      with Takai's (gamma-methoxyallyl)chromium reagent 40 are also described. The
      stereoselectivity of these reactions is also highly dependent on the protecting
      groups and stereochemistry of the chiral aldehyde substrates.

PMID- 12054964
TI  - An NMR method for assigning relative stereochemistry to beta-hydroxy ketones
      deriving from aldol reactions of methyl ketones.
AB  - We describe a simple 1H NMR analysis that permits the stereochemistry of beta
      hydroxy ketones to be assigned by visual inspection of the ABX patterns for the
      alpha-methylene unit of the beta-hydroxy ketone in the 1H NMR spectra. This
      method has been verified by application to a wide range of beta-hydroxy ketones
      deriving from aldol reactions of chiral aldehydes with a variety of chiral and
      achiral methyl ketone enolates (see Tables 1 and 2). The stereochemistry of 54 of
      these compounds have been assigned by rigorous chemical methods.

PMID- 12054965
TI  - Cyclic tetraselenadiynes: rigid cycles with long-range van der Waals forces
      between chalcogen centers.
AB  - The synthesis of cyclic tetraselenadiynes could be achieved by a stepwise
      approach. Key steps were the reaction of the lithium salt of
      trimethylsilylacetylene (1) with alpha,omega-diselenocyanatoalkanes 2(m) (m = 2
      5). By treating the bis-lithium salt of the resulting alpha,omega
      diselenaalkadiynes 4(m) (m = 2-5) again with 2(n) (n = 2-5) the cyclic
      tetraselenadiynes 5(m.n) resulted, with methylene chains of length m and n
      between the SeC triple bond CSe units. The structures of seven ring systems could
      be investigated in the solid state. These investigations reveal that the
      molecular structures are determined by the rigid SeC triple bond CSe units, which
      try to adopt torsion angles of the CH(2)-Se sigma-bonds between 60 degrees and 90
      degrees. In the solid state, the systems 5(3.3) and 5(5.5) show columnar
      structures that can be traced back to close contacts between Se atoms of
      neighboring rings.

PMID- 12054966
TI  - NMR and ab initio studies of amination of ketenimine: direct evidence for a
      mechanism involving a vinylidenediamine as an intermediate.
AB  - High-level ab initio calculations were carried out in both gas phase and solvent
      (epsilon = 35.9) to estabilish that the amination of ketenimine proceeds via
      amine addition across the C=N bond rather than the C=C bond, followed by
      tautomerization to form amidine product. The HOMO of ketenimine is perpendicular
      to its molecular plane with the largest coefficient on C(beta), while the LUMO is
      in its molecular plane with the largest coefficient on C(alpha). Amination of
      ketenimine involves in-plane attack of amine nucleophile on C(alpha) (LUMO) of
      ketenimine. The labile vinylidenediamine intermediate trans-11 for the reaction
      of ketenimine 10 with n-butylamine was directly observed by means of low
      temperature proton NMR spectra. The evidence confirms that the amination reaction
      is stepwise and proceeds via n-butylamine addition across the C=N bond of
      ketenimine 10 rather than the C=C bond, followed by a slower tautomerization of
      vinylidenediamine trans-11 to amidine 12. Even though the second step is much
      slower, the first step involving amine addition across the C=N bond is kinetic
      control. Surprisingly, in the reaction of 10 with n-BuNH(2), attack of n-BuNH(2)
      syn to the phenyl group on C(beta) of 10 is preferred, even though this produces
      a less stable product (trans-11); attack of n-BuNH(2) anti to phenyl group on
      C(beta) of 10 is lacking and results in serious nonbonding interactions between
      the two phenyls of the ketenimine, as they are pushed together in this transition
      state.

PMID- 12054968
TI  - Kinetic and mechanistic investigation of the aminolysis of 3-methoxyphenyl 3
      nitrophenyl thionocarbonate, 3-chlorophenyl 3-nitrophenyl thionocarbonate, and
      bis(3-nitrophenyl) thionocarbonate.
AB  - The reactions of the title thionocarbonates (6, 7, and 8, respectively) with a
      series of secondary alicyclic amines are subjected to a kinetic investigation in
      44 wt % ethanol-water, 25.0 degrees C, ionic strength 0.2 M (KCl). Under excess
      amine, pseudo-first-order rate coefficients (k(obsd)) are obtained for all
      reactions. Reactions of substrates 6 and 7 with piperidine and of thionocarbonate
      8 with the same amine and piperazine, 1-(2-hydroxyethyl)piperazine, and
      morpholine show linear k(obsd) vs [amine] plots, with slopes (k(1)) independent
      of pH. On the other hand, these plots are nonlinear upward for the reactions of
      substrates 6 and 7 with all the amines, except piperidine, and also for the
      reactions of compound 8 with 1-formylpiperazine and piperazinium ion. For all
      these reactions a mechanistic scheme is proposed with the formation of a
      zwitterionic tetrahedral intermediate (T(+/-)), which can transfer a proton to an
      amine to give an anionic intermediate (T(-)). Rate and equilibrium
      microcoefficients of this scheme, k(1), k(-)(1), K(1) (= k(1)/k(-)(1)), and k(2),
      are obtained by fitting the nonlinear plots through an equation derived from the
      scheme. The Bronsted-type plots for k(1) are linear with slopes beta(1) = 0.19,
      0.21, and 0.26 for the aminolysis of 6, 7, and 8, respectively. This is
      consistent with the hypothesis that the formation of T(+/-) (k(1) step) is the
      rate-determining step. The k(1) values for these reactions follow the sequence 8
      > 7 > 6, consistent with the sequence of the electron-withdrawing effects from
      the substituents on the "nonleaving" group of the substrates. The k(1) values for
      the aminolysis of 6, 7, and 8 are smaller than those for the same aminolysis of 3
      methoxyphenyl, 3-chlorophenyl, and 4-cyanophenyl 4-nitrophenyl thionocarbonates
      (2, 3, and 4, respectively). The k(2) values (expulsion of the nucleofuge from
      T(+/-)) increase as the electron withdrawal from the nonleaving group increases.
      These values are smaller for the aminolysis of 6, 7, and 8 compared to those for
      the same aminolysis of 2, 3, and 4, respectively.

PMID- 12054967
TI  - 2-pyridones from cyanoacetamides and enecarbonyl compounds: application to the
      synthesis of nothapodytine B.
AB  - The condensation of an enone or enal with cyanoacetamide derivatives and t-BuOK
      furnishes either 3-cyano-2-pyridones or 3-unsubstituted-2-pyridones, depending on
      whether the reaction is carried out in the presence or in the absence of O(2). In
      the first case, in situ oxidation of Michael-type intermediates takes place; in
      the second case, the products result from "decyanidative aromatization" of such
      intermediates. A one-step synthesis of 3-alkyl-2-pyridones has been devised on
      the basis of decyanative union of an enone/enal and a 2-alkylcyanoacetamide. The
      new reaction forms the centerpiece of an unusually concise synthesis of
      nothapodytine B (mappicine ketone).

PMID- 12054969
TI  - Studies on the synthesis of (-)-spinosyn a: application of the steric directing
      group strategy to transannular Diels-Alder reactions.
AB  - A highly diastereoselective and enantioselective synthesis of the decahydro-as
      indacene nucleus 12 of (-)-spinosyn A (1) is reported. By implementing the steric
      directing group strategy, tricyclic lactone 37 was produced from a remarkably
      diastereoselective transannular Diels-Alder reaction of lactone 9. The tricyclic
      core of the natural product was then obtained by using an Ireland-Claisen ring
      contraction of 37. Reversal of the order of these two steps resulted in an almost
      complete loss of diastereoselectivity.

PMID- 12054970
TI  - A new approach to (-)-swainsonine by ruthenium-catalyzed ring rearrangement.
AB  - A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in
      40% overall yield starting from the known oxazolidinone 6 is described.
      Throughout the synthesis, the high efficiency of metal-catalyzed reactions is
      illustrated. The key step is a new ruthenium-catalyzed metathesis rearrangement
      reaction. In this ring-closing/ring-opening tandem process, stereocenters are
      transferred from a ring to the olefinic side chain of the formed heterocycle. The
      metathesis precursor was obtained by palladium-catalyzed desymmetrization of
      cyclopentenediol. The synthesis was completed by functionalization of the
      terminal double bond, cyclization of the second ring, and diastereoselective
      dihydroxylation.

PMID- 12054971
TI  - Reactions of 5-, 6-, 7-, 8-hydroxyquinolines and 5-hydroxyisoquinoline with
      benzene and cyclohexane in superacids.
AB  - Isomeric 5-, 6-, 7-hydroxyquinolines (11-13) and 5-hydroxyisoquinoline (14) gave
      N,C-diprotonated dications in CF(3)SO(3)H-SbF(5) superacid medium. Compounds 11,
      13, 14, and 8-hydroxyquinoline (5) underwent selective ionic hydrogenation with
      cyclohexane in the presence of aluminum chloride. Compounds 11 and 14 condense
      with benzene in the presence of aluminum halides. The detailed mechanism of
      reactions, which involves superelectrophilic dicationic intermediates, is
      discussed.

PMID- 12054972
TI  - Stereoselective total syntheses of the racemic form and the natural enantiomer of
      the marine alkaloid lepadiformine via a novel N-acyliminium ion/allylsilane
      spirocyclization strategy.
AB  - Stereoselective total syntheses of the racemic form and the natural enantiomer of
      the tricyclic marine alkaloid lepadiformine (6) have been accomplished using a
      novel intramolecular spirocyclization of an N-acyliminium ion with an allylsilane
      to form the A/C rings as the key step. Introduction of the hydroxymethyl group at
      C-13 of the racemic spirocycle 11 was achieved using our methodology for
      oxidative radical-based remote functionalization of o-aminobenzamides, followed
      by copper-catalyzed addition of Grignard reagent 16 to the N-acyliminium ion
      intermediate derived from 15. Subsequent Tamao oxidation of silane 17 then
      afforded the requisite hydroxymethyl compound 19, which was converted to the
      dimethyl acetal 25 via hydroformylation followed by aldehyde protection.
      Hydrolysis of the benzamide moiety of 25 and subsequent protection of the primary
      alcohol gave amino acetal 27. The synthesis was concluded from 27 by a four-step
      procedure: acid-catalyzed ring closure, amino nitrile formation, introduction of
      the hexyl chain by a Grignard reaction to an iminium salt, and removal of the O
      benzyl protecting group to give (+/-)-lepadiformine (6). The enantioselective
      total synthesis of 6 started from known optically pure bromide 37, derived from
      (S)-pyroglutamic acid, and followed a similar sequence involving the key
      spirocyclization of N-acyliminium ion 42. This synthesis has established the
      absolute configuration of naturally occurring lepadiformine to be
      2(R),5(S),10(S),13(S).

PMID- 12054973
TI  - First total synthesis of A(2) isoprostane.
AB  - A stereoselective Julia-Lythgoe olefination has allowed the first total synthesis
      of A(2) isoprostane (1), a recently discovered member of the growing isoprostane
      family. This elusive compound opens up numerous new avenues for the molecular
      biology of cyclopentenone prostaglandins, which are endowed of intriguing
      biological effects such as antitumor, antiinflammatory, and antiviral activities.

PMID- 12054974
TI  - Optically active aromatic and heteroaromatic alpha-amino acids by a one-pot
      catalytic enantioselective addition of aromatic and heteroaromatic C-H bonds to
      alpha-imino esters.
AB  - The development of a practical one-pot catalytic enantioselective procedure for
      the synthesis of non-natural aromatic and heteroaromatic alpha-amino acids is
      reported. Starting from readily available starting materials and application of a
      chiral BINAP-Cu(I) catalyst, the optically active products are formed with
      readily removable N-protecting groups. The scope of the reaction is demonstrated
      by the addition of substituted furans, thiophenes, pyrroles, and aromatic
      compounds to N-alkoxycarbonyl-alpha-imino esters in good yields and with
      enantioselectivities up to 96% ee for the furans, 93% ee for the thiophenes, and
      98% for the aromatic compounds. The protecting groups are readily removed, and
      various transformations of the aromatic and heteroaromatic alpha-amino acids are
      demonstrated. The coordination of the N-alkoxycarbonyl alpha-imino ester to the
      chiral BINAP-Cu(I) complex and the enantioselectivity of the catalyst is
      discussed on the basis of the DFT calculations and X-ray crystallographic data.

PMID- 12054975
TI  - Reactivities of novel [hydroxy(tosyloxy)iodo]arenes and
      [hydroxy(phosphoryloxy)iodo]arenes for alpha-tosyloxylation and alpha
      phosphoryloxylation of ketones.
AB  - Novel [hydroxy(tosyloxy)iodo]arenes bearing 2-thienyl, 3-thienyl, N-tosyl-4
      pyrazolyl, 3-trifluoromethylphenyl, and 3,5-bis(trifluoromethy)phenyl as an
      aromatic group, and [hydroxy(phosphoryloxy)iodo]arenes bearing N-tosyl-4
      pyrazolyl, 3-trifluoromethylphenyl, and 3,5-bis(trifluoromethy)phenyl as an
      aromatic group, were prepared. alpha-Tosyloxylation and alpha-phosphoryloxylation
      of ketones with these compounds were carried out, respectively. Their
      reactivities were compared with that of the parent [hydroxy(tosyloxy)iodo]benzene
      and [hydroxy(phosphoryloxy)iodo]benzene, respectively, and consequently
      [hydroxy(tosyloxy)iodo]arenes and [hydroxy(phosphoryloxy)iodo]arenes bearing 3
      trifluoromethylphenyl and 3,5-bis(trifluoromethy)phenyl as an aromatic group
      showed the best reactivity. These new compounds can be used as powerful alpha
      tosyloxylation and alpha-phosphoryloxylation reagents, instead of the parent
      [hydroxy(tosyloxy)iodo]benzene and [hydroxy(phosphoryloxy)iodo]benzene.

PMID- 12054976
TI  - Asymmetric synthesis of silylated alpha-amino acid esters through dynamic kinetic
      resolution.
AB  - Esters of three types of silylated alpha-amino acids have been prepared from
      appropriate zirconaaziridines. Slow addition (syringe pump) of the (R,R)
      carbonate of trans-stilbene gave metallacycles with the maximum possible
      diastereomeric excess (as determined by the diastereomeric excess produced by the
      Hoffmann test-the same reaction but with racemic carbonate). Methanolysis gave
      esters (RO(2)C)CH(R')(NHPh) (R' = Me(3)Si, Me(3)SiCH(2), and p-Me(3)SiC(6)H(4))
      with the same optical purity at the alpha carbon.

PMID- 12054977
TI  - Hammett rho of reactions of MeLi with benzophenones.
AB  - Relative rates of reactions of MeLi with benzophenones in diethyl ether at 0
      degrees C that furnish methyldiarylmethanols were determined using slow addition
      of a MeLi solution to solutions containing an excess of two benzophenones. The
      additions exhibit a Hammett rho of 0.94.

PMID- 12054978
TI  - A concise synthesis of beta-asparaginyladenylate.
AB  - Stable analogues of acyladenylate intermediates, such as N-acylphosphoramidates,
      are useful probes of tRNA aminoacylation and enzyme mechanism, and have potential
      application as enzyme inhibitors. We now report a concise, "one-pot" synthesis of
      beta-asparaginyladenylate using a novel coupling protocol that yields the target
      N-acylphosphoramidate in three reactions from readily available precursors. This
      simple synthetic procedure may represent a general approach for the preparation
      of functionalized N-acylphosphoramidates from amides that do not undergo coupling
      under the conditions of existing literature protocols.

PMID- 12054979
TI  - Palladium-indium-mediated arylative cyclization of allenyl-aldehydes and 
      ketones.
AB  - The arylative cyclization of allenyl-aldehydes and -ketones to form homoallylic
      cyclopentanols and cyclohexanols by the palladium-catalyzed and indium-mediated
      Babier allylation is described.

PMID- 12054980
TI  - Intramolecular cycloadditions of alpha-allyloxycarbonylnitrones: stereoselective
      synthesis of 3-amino-2(5H)furanones.
AB  - Treatment of furoisoxazolidines with NaH leads to functionalized 3-amino-2(5H)
      furanones through a new rearrangement pattern of the isoxazolidine nucleus. This
      process has been usefully exploited for the synthesis of enantiomerically pure
      (5R)-3-alkylamino-5-methyl-2(5H)-furanones.

PMID- 12054981
TI  - New fluorescent chemosensors for silver ion.
AB  - New fluorescent chemosensors, 1,8-bis(pyrazolylmethyl)anthracene and 9,10
      bis(pyrazolylmethyl)anthracene, were synthesized. The 1,8-isomer showed selective
      fluorescent quenching effects with Ag(I) and Cu(II). On the other hand, the 9,10
      isomer displayed a selective fluorescent quenching effect only with Ag(I). From
      the association constants obtained from fluorescent titrations and by extraction,
      we conclude that rigid immobilization of the ligands, 1,8-isomer, plays a more
      important role in the binding with Ag(I) than the additional pi-cation
      interaction offered by the 9,10-isomer.

PMID- 12054982
TI  - Giant metal-cyanide coordination clusters: tetracapped edge-bridged cubic
      Cr(12)Ni(12)(CN)(48) and double face-centered cubic Cr(14)Ni(13)(CN)(48) species.
AB  - The crystal structures of two new metal-cyanide clusters with record high
      nuclearities are reported. A direct assembly reaction involving
      [(Me(3)tacn)Cr(CN)(3)] (Me(3)tacn = N,N',N"-trimethyl-1,4,7-triazacyclononane),
      NiI(2), and KCN in aqueous solution affords
      [(Me(3)tacn)(12)Cr(12)Ni(12)(CN)(48)](12+). The structure of this 24-metal
      cluster features a cube of eight Cr(III) centers linked along the edges by 12
      trans-coordinated [Ni(CN)(4)](2)(-) units, and capped on four faces by
      [(Me(3)tacn)Cr](3+) moieties. Its metal-cyanide cage encloses a 900 A(3) cavity
      that is accessible through the two noncapped cube faces. A still larger cluster,
      [(Me(3)tacn)(14)Cr(14)Ni(13)(CN)(48)](20+), was obtained from a related reaction
      excluding the addition of KCN. This 27-metal species possesses a highly
      anisotropic geometry in which two face-centered cubic units are fused through a
      common Ni(II) vertex.

PMID- 12054983
TI  - Synthesis and characterization of phosphorescent cyclometalated platinum
      complexes.
AB  - The synthesis, electrochemistry, and photophysics of a series of square planar
      Pt(II) complexes are reported. The complexes have the general structure
      C(wedge)NPt(O(wedge)O),where C(wedge)N is a monoanionic cyclometalating ligand
      (e.g., 2-phenylpyridyl, 2-(2'-thienyl)pyridyl, 2-(4,6-difluorophenyl)pyridyl,
      etc.) and O(wedge)O is a beta-diketonato ligand. Reaction of K(2)PtCl(4) with a
      HC(wedge)N ligand precursor forms the chloride-bridged dimer, C(wedge)NPt(mu
      Cl)(2)PtC(wedge)N, which is cleaved with beta-diketones such as acetyl acetone
      (acacH) and dipivaloylmethane (dpmH) to give the corresponding monomeric
      C(wedge)NPt(O(wedge)O) complex. The thpyPt(dpm) (thpy = 2-(2'-thienyl)pyridyl)
      complex has been characterized using X-ray crystallography. The bond lengths and
      angles for this complex are similar to those of related cyclometalated Pt
      complexes. There are two independent molecular dimers in the asymmetric unit,
      with intermolecular spacings of 3.45 and 3.56 A, consistent with moderate pi-pi
      interactions and no evident Pt-Pt interactions. Most of the
      C(wedge)NPt(O(wedge)O) complexes display a single reversible reduction wave
      between -1.9 and -2.6 V (vs Cp(2)Fe/Cp(2)Fe(+)), assigned to largely C(wedge)N
      ligand based reduction, and an irreversible oxidation, assigned to predominantly
      Pt based oxidation. DFT calculations were carried out on both the ground
      (singlet) and excited (triplet) states of these complexes. The HOMO levels are a
      mixture of Pt and ligand orbitals, while the LUMO is predominantly C(wedge)N
      ligand based. The emission characteristics of these complexes are governed by the
      nature of the organometallic cyclometalating ligand allowing the emission to be
      tuned throughout the visible spectrum. Twenty-three different C(wedge)N ligands
      have been examined, which gave emission lambda(max) values ranging from 456 to
      600 nm. Well-resolved vibronic fine structure is observed in all of the emission
      spectra (room temperature and 77 K). Strong spin-orbit coupling of the platinum
      atom allows for the formally forbidden mixing of the (1)MLCT with the (3)MCLT and
      (3)pi-pi states. This mixing leads to high emission quantum efficiencies (0.02
      0.25) and lifetimes on the order of microseconds for the platinum complexes.

PMID- 12054984
TI  - Chemical vapor deposition of gallium nitride from the GaCl(3)+NH(3) system.
      Theoretical study of the structure and thermodynamics of potential intermediates
      formed in the gaseous phase.
AB  - Quantum chemical calculations at the B3P86/6-311G(d,p) level have been performed
      on potential intermediate molecules in the chemical vapor deposition (CVD) of GaN
      from the GaCl(3) + NH(3) system. The investigated molecules included the monomer
      (Cl(x)GaNH(x), x = 1-3) and oligomer species (Cl(2)GaNH(2))(n) with n = 1-3 and
      (ClGaNH)(n) with n = 1-4 as well as the respective chain dimers and trimers. The
      calculations revealed the importance of intramolecular Cl...H hydrogen bonding
      and dipole-dipole interactions in determining the conformational properties of
      the larger species. Except for the ClGaNH monomer, the Ga[bond]N bonding has a
      single bond character with a strong ionic contribution. Our thermodynamic study
      of the composition of the gaseous phase supported the predominance of the
      Cl(3)GaNH(3) complex under equilibrium conditions. Additionally, the calculated
      Gibbs free energies of various GaCl(3) + NH(3) reactions imply the favored
      formation of "saturated" chain and cyclic oligomers below 1000 K.

PMID- 12054985
TI  - Kinetic study of the oxidation of catechol by aqueous copper(II).
AB  - The kinetics of the oxidation of catechol by aqueous copper(II) have been studied
      as a function of reactant concentrations at pH 6.4-7.2. To follow the reaction, a
      spectrophotometric method has been developed that circumvents the problem of
      precipitation of decomposition products of the initial o-quinone oxidation
      product. The rate law shows that the reactive species is the monocatecholate
      complex of Cu(II), and that this species undergoes rate-limiting intramolecular
      electron transfer with k = 1.9 x 10(-5) s(-1) (22 +/- 1 degrees C, mu = 0.125 M
      NaClO(4)). The results have allowed a reanalysis of previous work on the
      autoxidation in the aqueous Cu(II)-catechol-dioxygen system, and comparisons to
      mechanisms of copper(II) oxidases.

PMID- 12054986
TI  - Synthesis and reactivity of 1,2-bis(chlorodimethylgermyl)carborane and 1,2
      bis(bromodimethylstannyl)carborane.
AB  - The 1,2-bis(chlorogermyl)- (1) and 1,2-bis(bromostannyl)carborane (2) have been
      prepared by the reaction of dilithio-o-carborane with Me(2)GeCl(2) and
      Me(2)SnBr(2), respectively. Compounds 1 and 2 are found to be good precursors for
      the synthesis of a variety of cyclization compounds. The Wurtz-type coupling
      reaction of 1 and 2 using sodium metal afforded the four-membered digerma
      compound 3 and five-membered tristanna compound 4, respectively. The salt
      elimination reactions of 1 and 2 using Li(2)N(t)Bu and Li(2)PC(6)H(5) afforded
      the cyclic products [structure: see text]. The 1,2-bis(dimethylgermyl)carborane 9
      and 1,2-bis(dimethylstannyl)carborane 10 were prepared by the reaction of 1 and 2
      with sodium cyanoborohydride. The reactions of 9 and 10 with Pd(PPh(3))(4)
      afforded the bis(germyl)palladium 12 and bis(stannyl)palladium 13 complexes,
      respectively.

PMID- 12054987
TI  - Interpretation of indirect nuclear spin-spin coupling tensors for polyatomic
      xenon fluorides and group 17 fluorides: results from relativistic density
      functional calculations.
AB  - Significant improvements have been made recently in the calculation of NMR
      indirect nuclear spin-spin coupling tensors (J). In particular, the relativistic
      zeroth-order regular approximation density-functional theory (ZORA-DFT) approach
      holds great promise for the calculation of spin-spin coupling constants for a
      variety of chemical systems containing heavy nuclei. In the present work, the
      ZORA-DFT method is applied to the calculation of the complete reduced coupling
      tensors, K, for a range of chlorine-, bromine-, iodine-, and xenon-containing
      species: K(Cl,F) for ClF(2)(+), ClF(3), ClF(4)(+), ClF(5), ClF(6)(-), and
      ClF(6)(+); K(Br,F) for BrF(3), BrF(6)(-), and BrF(6)(+); K(I,F) for IF(4)(+) and
      IF(6)(+); K(Xe,F) for XeF(+), XeF(2), XeF(3)(+), XeF(4), XeF(5)(-), XeF(5)(+),
      and XeF(7)(+). These species represent a wide variety of geometrical bonding
      arrangements. Agreement between the calculated coupling constants and available
      experimental data is excellent, and the absolute sign of the coupling constants
      is provided. It is shown that (1)K(iso) may be positive or negative even within
      the same molecule, e.g., K(Cl,F)(iso) may be of either sign, depending on the
      local environment. Periodic trends in (1)K(iso) for isovalent and isostructural
      molecules are evident. The spin-spin coupling anisotropies, Delta K, and the
      orientations of the K tensors are also determined. The success of the
      calculations is a direct result of employing reliable geometries and considering
      both scalar and spin-orbit relativistic effects. The dependence of K(Cl,F)(iso)
      and K(Xe,F)(iso) on the local molecular and electronic structure is discussed in
      terms of the paramagnetic spin-orbit (PSO) and combined Fermi-contact spin
      dipolar (FC+SD) coupling mechanisms. The PSO term depends strongly on the number
      of valence shell electron lone pairs on the central heavy atom, and the FC+SD
      contribution increases with the Cl[bond]F or Xe[bond]F bond length for a given
      series of compounds. This interpretation allows for the successful
      rationalization of the existing experimental data.

PMID- 12054989
TI  - Steric control of substituted phenoxide ligands on product structures of uranyl
      aryloxide complexes.
AB  - A series of uranyl aryloxide complexes has been prepared via metathesis reactions
      between [UO(2)Cl(2)(THF)(2)](2) and di-ortho-substituted phenoxides. Reaction of
      4 equiv of KO-2,6-(t)()Bu(2)C(6)H(3) with [UO(2)Cl(2)(THF)(2)](2) in THF produces
      the dark red uranyl compound, UO(2)(O-2,6-(t)()Bu(2)C(6)H(3))(2)(THF)(2).THF, 1.
      Single-crystal X-ray diffraction analysis of 1 reveals a monomer in which the
      uranium is coordinated in a pseudooctahedral fashion by two apical oxo groups,
      two cis-aryloxides, and two THF ligands. A similar product is prepared by
      reaction of KO-2,6-Ph(2)C(6)H(3) with [UO(2)Cl(2)(THF)(2)](2) in THF. Single
      crystal X-ray diffraction analysis of this compound reveals it to be the trans
      monomer UO(2)(O-2,6-Ph(2)C(6)H(3))(2)(THF)(2), 2. Dimeric structures result from
      the reactions of [UO(2)Cl(2)(THF)(2)](2) with less sterically imposing aryloxide
      salts, KO-2,6-Cl(2)C(6)H(3) or KO-2,6-Me(2)C(6)H(3). Single-crystal X-ray
      diffraction analyses of [UO(2)(O-2,6-Cl(2)C(6)H(3))(2)(THF)(2)](2), 3, and
      [UO(2)Cl(O-2,6-Me(2)C(6)H(3))(THF)(2)](2), 4, reveal similar structures in which
      each U atom is coordinated by seven ligands in a pseudopentagonal bipyramidal
      fashion. Coordinated to each uranium are two apical oxo groups and five
      equatorial ligands (3, one terminal phenoxide, two bridging phenoxides, and two
      nonadjacent terminal THF ligands; 4, one terminal chloride, two bridging
      phenoxides, and two nonadjacent terminal THF ligands). Apparently, the phenoxide
      ligand steric features exert a greater influence on the solid-state structures
      than the electronic properties of the substituents. Emission spectroscopy has
      been utilized to investigate the molecularity and electronic structure of these
      compounds. For example, luminescence spectra taken at liquid nitrogen temperature
      allow for a determination of the dependence of the molecular aggregation of 3 on
      the molecular concentration. Electronic and vibrational spectroscopic
      measurements have been analyzed to examine trends in emission energies and
      stretching frequencies. However, comparison of the data for compounds 1-4 reveals
      that the innate electron-donating capacity of phenoxide ligands is only subtly
      manifest in either the electronic or vibrational energy distributions within
      these molecules.

PMID- 12054988
TI  - Structural, spectroscopic, and reactivity comparison of xanthene- and
      dibenzofuran-bridged cofacial bisporphyrins.
AB  - A comparison of the structure, spectroscopy, and oxygen atom-transfer reactivity
      of cofacial bisporphyrins anchored by xanthene (DPX) and dibenzofuran (DPD)
      pillars is presented. The synthesis and characterization of dicopper(II) and
      dinickel(II) complexes of DPD completes a homologous series of homobimetallic
      zinc(II), copper(II), and nickel(II) complexes for both cofacial platforms. X-ray
      crystallographic analysis of the parent free-base porphyrins H(4)DPX (1) and
      H(4)DPD (5) confirms the face-to-face arrangement of the two porphyrin
      macrocycles with a large available range of vertical pocket sizes: 1
      (C(80)H(92)Cl(2)N(8)O), triclinic, space group P1 macro, a = 13.5167(12) A, b =
      21.7008(18) A, c = 23.808(2) A, alpha = 80.116(2) degrees, beta = 76.832(2)
      degrees, gamma = 80.4070(10) degrees, Z = 4; 5 (C(80)H(83)N(8)O(2)), monoclinic,
      space group C2/c, a = 22.666(2) A, b = 13.6749(14) A, c = 42.084(4) A, beta =
      94.554(2) degrees, Z = 8. EPR spectroscopy of dicopper(II) derivatives Cu(2)DPX
      (3) and Cu(2)DPD (7) complements the crystallographic studies by probing
      intramolecular metal-metal arrangements in frozen solution. Exciton interactions
      between the porphyrin subunits in fluid solution are revealed by steady-state and
      time-resolved electronic absorption and emission spectroscopy. The resulting
      compilation of structural and spectroscopic data provides a benchmark for the use
      of these and related platforms for the activation of small-molecule substrates. A
      structure-function relation is developed for the photoinduced oxygen atom
      transfer reactions of bisiron(III) mu-oxo derivatives of DPX and DPD. The
      efficiency of the photochemical process is markedly dependent (approximately
      10(4)-fold) on the vertical flexibility of cofacial architecture provided by the
      spacer.

PMID- 12054990
TI  - Site-selective EXAFS in mixed-valence compounds using high-resolution
      fluorescence detection: a study of iron in Prussian Blue.
AB  - A quantitative analysis is presented for the site-selective Fe K-edge absorption
      spectra of Prussian Blue: Fe(4)[Fe(CN)(6)](3) x xH(2)O (x = 14-16). The site
      selective spectra were recorded using high-resolution fluorescence detection of
      the K beta emission from a polycrystalline sample. The K beta fluorescence lines
      arising from the high-spin and low-spin sites are shifted in energy. Since the
      emission features partially overlap, fluorescence-detected absorption spectra
      using different emission energies represent different linear combinations of the
      pure high-spin and low-spin EXAFS. A numerical method was used to extract the
      individual site EXAFS spectra from the experimental data. The analysis yields a
      range of solutions. A unique solution can be obtained if homovalent model
      compounds are used to simulate the K beta fluorescence emission from the two Fe
      sites in Prussian Blue. EXAFS analysis of the range of spectra obtained in the
      numerical method yields almost identical interatomic distances for the different
      spectra while the Debye-Waller factors vary considerably. The distances obtained
      in the EXAFS fit correspond to the crystallographic distances.

PMID- 12054992
TI  - Substitution reactions of [Ru(dppe)(CO)(H(2)O)(3)][OTf](2).
AB  - The labile nature of the coordinated water ligands in the organometallic aqua
      complex [Ru(dppe)(CO)(H(2)O)(3)][OTf](2) (1) (dppe = Ph(2)PCH(2)CH(2)PPh(2); OTf
      = OSO(2)CF(3)) has been investigated through substitution reactions with a range
      of incoming ligands. Dissolution of 1 in acetonitrile or dimethyl sulfoxide
      results in the facile displacement of all three waters to give
      [Ru(dppe)(CO)(CH(3)CN)(3)][OTf](2) (2) and [Ru(dppe)(CO)(DMSO)(3)][OTf](2) (3),
      respectively. Similarly, 1 reacts with Me(3)CNC to afford
      [Ru(dppe)(CO)(CNCMe(3))(3)][OTf](2) (4). Addition of 1 equiv of 2,2'-bipyridyl
      (bpy) or 4,4'-dimethyl-2,2'-bipyridyl (Me(2)bpy) to acetone/water solutions of 1
      initially yields [Ru(dppe)(CO)(H(2)O)(bpy)][OTf](2) (5a) and
      [Ru(dppe)(CO)(H(2)O)(Me(2)bpy)][OTf](2) (6a), in which the coordinated water lies
      trans to CO. Compounds 5a and 6a rapidly rearrange to isomeric species (5b, 6b)
      in which the ligated water is trans to dppe. Further reactivity has been
      demonstrated for 6b, which, upon dissolution in CDCl(3), loses water and
      coordinates a triflate anion to afford [Ru(dppe)(CO)(OTf)(Me(2)bpy)][OTf] (7).
      Reaction of 1 with CH(3)CH(2)CH(2)SH gives the dinuclear bridging thiolate
      complex [[(dppe)Ru(CO)](2)(mu-SCH(2)CH(2)CH(3))(3)][OTf] (8). The reaction of 1
      with CO in acetone/water is slow and yields the cationic hydride complex
      [Ru(dppe)(CO)(3)H][OTf] (9) via a water gas shift reaction. Moreover, the same
      mechanism can also be used to account for the previously reported synthesis of 1
      upon reaction of Ru(dppe)(CO)(2)(OTf)(2) with water (Organometallics 1999, 18,
      4068).

PMID- 12054991
TI  - Enhancing reactivity via structural distortion.
AB  - To examine how small structural changes influence the reactivity and magnetic
      properties of biologically relevant metal complexes, the reactivity and magnetic
      properties of two structurally related five-coordinate Fe(III) thiolate compounds
      are compared. (Et,Pr)-ligated [Fe(III)(S(2)(Me2)N(3)(Et,Pr))]PF(6) (3) is
      synthesized via the abstraction of a sulfur from alkyl persulfide ligated
      [Fe(III)(S(2)(Me2)N(3)(Et,Pr))-S(pers)]PF(6) (2) using PEt(3). (Et,Pr)-3 is
      structurally related to (Pr,Pr)-ligated [Fe(III)(S(2)(Me2)N(3)(Pr,Pr))]PF(6) (1),
      a nitrile hydratase model compound previously reported by our group, except it
      contains one fewer methylene unit in its ligand backbone. Removal of this
      methylene distorts the geometry, opens a S-Fe-N angle by approximately 10
      degrees, alters the magnetic properties by stabilizing the S = 1/2 state relative
      to the S = 3/2 state, and increases reactivity. Reactivity differences between 3
      and 1 were assessed by comparing the thermodynamics and kinetics of azide
      binding. Azide binds reversibly to both (Et,Pr)-3 and (Pr,Pr)-1 in MeOH
      solutions. The ambient temperature K(eq) describing the equilibrium between five
      coordinate 1 or 3 and azide-bound 1-N(3) or 3-N(3) in MeOH is approximately 10
      times larger for the (Et,Pr) system. In CH(2)Cl(2), azide binds approximately 3
      times faster to 3 relative to 1, and in MeOH, azide dissociates 1 order of
      magnitude slower from 3-N(3) relative to 1-N(3). The increased on rates are most
      likely a consequence of the decreased structural rearrangement required to
      convert 3 to an approximately octahedral structure, or they reflect differences
      in the LUMO (vs SOMO) orbital population (i.e., spin-state differences).
      Dissociation rates from both 3-N(3) and 1-N(3) are much faster than one would
      expect for low-spin Fe(III). Most likely this is due to the labilizing effect of
      the thiolate sulfur that is trans to azide in these structures.

PMID- 12054993
TI  - Linear heterotrinuclear complexes derived from an alkyl platinum(II) twelve
      membered macrocycle.
AB  - The P,N,P-tridentate ligand 2,6-bis(diphenylphosphino)pyridine, L, was employed
      to generate a twelve-membered metallomacrocyclic host species cis-Pt(2)Me(4)(mu
      L)(2) that encapsulates Tl(I) and Cu(I) guest ions. The ligand was also used to
      synthesize another two linear heterotrinuclear complexes, [Me(2)Pt(mu
      L)(2)Ag(2)(MeCN)(2)](BF(4))(2).MeCN and [(CO)(3)Fe(mu
      L)(2)Ag(2)(Et(2)O)](ClO(4))(2), both containing a metal-metal dative bond (Pt-
      >Ag and Fe-->Ag, respectively) and stabilized by the d(10)-d(10) argentophilic
      interaction.

PMID- 12054994
TI  - Excited state properties of mixed phosphine 2-(2'-pyridyl)quinoline complexes of
      ruthenium(II).
AB  - Mixed ligand complexes of the type Ru(pq)(2)(PP)(2+) (pq = 2,2'-pyridylquinoline
      and PP = one bidentate or two monodentate phosphine ligands) have been prepared
      from the appropriate phosphine and Ru(pq)(2)Cl(2). The room temperature
      absorption spectra and low temperature (77 K) emission spectra, emission
      lifetimes, and quantum yields have been measured for the series of complexes and
      compared with those of Ru(pq)(3)(2+) and analogous Ru(bpy)(2)(PP)(2+) complexes
      (bpy = 2,2'-bipyridine) where possible. Emission spectra have been fit using a
      single mode Franck-Condon analysis. The visible absorption bands and emission
      bands are assigned to MLCT transitions that are blue shifted relative to
      Ru(pq)(3)(2+), while the emission lifetimes and quantum yields are increased. The
      trends in the nonradiative rate constants, k(nr), are described in terms of the
      energy gap, E(0), and the Huang-Rhys factor, S(M), which were obtained from the
      spectral fittings, and are correlated with the phosphine ligand structures.

PMID- 12054995
TI  - Syntheses of ruthenium(II) quinonediimine complexes of cyclam and
      characterization of their DNA-binding activities and cytotoxicity.
AB  - The synthesis and characterization of ruthenium(II) complexes, [Ru(cyclam)(bqdi)]
      x ZnCl(4) (1 x ZnCl(4); cyclam = 1,4,8,11-tetraazacyclotetradecane, bqdi = o
      benzoquinonediimine), [Ru(cyclam)(nqdi)] x (ClO(4))(2) (2 x (ClO(4))(2); nqdi =
      2,3-naphthoquinonediimine), and [Ru(cyclam)(phi)] x (ClO(4))(2) (3 x (ClO(4))(2);
      phi = 9,10-phenanthroquinonediimine), are described. The DNA binding properties
      and biological activity of the Ru(II) complexes were studied by various
      biophysical and cytological techniques. As expected, only 3 showed significant
      binding with DNA. The thermodynamic profile of the binding of 3 and DNA was
      constructed by analyzing the experimental data of absorption titration and UV
      melting studies with the McGhee equation, van't Hoff's equation, and the Gibbs
      Helmholtz equation. Compound 3 binds double-stranded DNA with a binding constant
      of 5.0 x 10(4) M(-1) at 20 degrees C, and the binding mode of the complex to DNA
      was proved to be intercalative. Cytotoxicity and induced type of cell death of 1
      3 were also investigated. Basically, metal complexes with ligands of molecular
      shape closely related to the structure of DNA are more likely to bind DNA and
      possess higher toxicity.

PMID- 12054996
TI  - Structural and spectroscopic studies of valence-delocalized diiron(II,III)
      complexes dupported by carboxylate-only bridging ligands.
AB  - The synthesis, molecular structures, and spectroscopic properties of a series of
      valence-delocalized diiron(II,III) complexes are described. One-electron
      oxidation of diiron(II) tetracarboxylate complexes afforded the compounds
      [Fe(2)(mu-O(2)CAr(Tol))(4)L(2)]X, where L = 4-(t)BuC(5)H(4)N (1b), C(5)H(5)N
      (2b), and THF (3b); X = PF(6)(-) (1b and 3b) and OTf(-) (2b). In 1b-3b, four mu
      1,3 carboxylate ligands span relatively short Fe...Fe distances of 2.6633(11)
      2.713(3) A. Intense (epsilon = 2700-3200 M(-1) cm(-1)) intervalence charge
      transfer bands were observed at 620-670 nm. EPR spectroscopy confirmed the S =
      (9)/(2) ground spin state of 1b-3b, the valence-delocalized nature of which was
      probed by X-ray absorption spectroscopy. The electron delocalization between
      paramagnetic metal centers is described by double exchange, which, for the first
      time, is observed in diiron clusters having no single-atom bridging ligand(s).

PMID- 12054997
TI  - Metal ion scrambling in hexanuclear M(6)(Et(2)NCO(2))(12) complexes (M = Co, Mg).
      Synthesis, solid state structure, and solution dynamics of heteronuclear
      Co(n)Mg(6-n)(Et(2)NCO(2))(12) complexes.
AB  - Heteronuclear diethylcarbamato complexes of the form Co(n)()Mg(6)(
      )(n)()(Et(2)NCO(2))(12) were prepared from the isostructural homonuclear
      precursors Mg(6)(Et(2)NCO(2))(12), 1, and Co(6)(Et(2)NCO(2))(12), 2, via a
      solvothermal methodology. Two materials were selected for single-crystal X-ray
      diffraction analysis: Co(1.6)Mg(4.4)(Et(2)NCO(2))(12) and
      Co(2.7)Mg(3.3)(Et(2)NCO(2))(12). Both compounds crystallize in the orthorhombic
      space group Ccca, as do 1 and 2. The molecular structure is best described as two
      trinuclear M(3) units cross-linked by diethylcarbamate ligands and twisted about
      one another, so that the complex has overall D(2) symmetry and is chiral. Each
      trinuclear unit consists of two terminal pentacoordinate metal ions and one
      central hexacoordinate metal ion. The X-ray diffraction data were unambiguous
      that the Co(2+) ions migrate exclusively to the pentacoordinate sites in the
      heteronuclear complexes, thus demonstrating that metal ion scrambling at the
      molecular level must occur. The composition of individual crystals can be
      continuously varied for Co(2+) mole fractions chi(Co) < 0.5, and the a and c unit
      cell distances are linearly related to chi(Co). This indicates that the compounds
      behave as solid solutions. There appears to be either a chemical or
      crystallographic phenomenon inherent in the synthetic methodology that prevents
      isolation of heteronuclear materials having chi(Co) > 0.5. Solution electronic
      spectroscopy and molecular weight measurements show that 2 can dissociate in
      chloroform and cyclohexane solution to give a dimeric complex 2'. This behavior
      contrasts with the stability of 1 in solution, as shown by NMR. The kinetic rate
      profile for formation of Co(n)Mg(6-n)(Et(2)NCO(2))(12) reveals saturation
      kinetics and is consistent with direct attack by 2' on 1 to give the
      heteronuclear complex via a higher nuclearity intermediate. This study
      illustrates a general method for the preparation of solids based on heteronuclear
      Werner-type complexes of the M(6)(Et(2)NCO(2))(12) structure type, and the
      mechanism by which such compounds can be formed from isostructural homonuclear
      precursors.

PMID- 12054999
TI  - Unprecedented cage-carbon to cage-boron NMe(3) transfer in a monocarbon
      Molybdenacarborane.
AB  - The reagent Li(2)[7-NMe(3)-nido-7-CB(10)H(10)] reacts with [Mo(CO)(3)(NCMe)(3)]
      in THF-NCMe (THF = tetrahydrofuran) to give a molybdenacarborane intermediate
      which, upon oxidation by CH(2)[double bond]CHCH(2)Br or I(2) and then addition of
      [N(PPh(3))(2)]Cl, gives the salts [N(PPh(3))(2)][2,2,2-(CO)(3)-2-X-3-NMe(3)-closo
      2,1-MoCB(10)H(10)] (X = Br (1) or I (2)). During the reaction, the cage-bound
      NMe(3) substituent is transferred from the cage-carbon atom to an adjacent cage
      boron atom, a feature established spectroscopically in 1 and 2, and by X-ray
      diffraction studies on several of their derivatives. When [Rh(NCMe)(3)(eta(5)
      C(5)Me(5))][BF(4)](2) is used as the oxidizing agent, the trimetallic compound
      [2,2,2-(CO)(3)-7-mu-H-2,7,11-[Rh(2)(mu-CO)(eta(5)-C(5)Me(5))(2)]-closo-2,1
      MoCB(10)H(9)] (10) is formed, the NMe(3) group being lost. Reaction of 1 in
      CH(2)Cl(2) with Tl[PF(6)] in the presence of donor ligands L affords neutral
      zwitterionic compounds [2,2,2-(CO)(3)-2-L-3-NMe(3)-closo-2,1-MoCB(10)H(10)] for L
      = PPh(3) (4) or CNBu(t) (5), and [2-Bu(t)C[triple bond]CH-2,2-(CO)(2)-3-NMe(3)
      closo-2,1-MoCB(10)H(10)] (6) when L = Bu(t)C[triple bond]CH. When 1 is treated
      with CNBu(t) and X(2), the metal center is oxidized, and in the products
      obtained, [2,2,2,2-(CNBu(t))(4)-2-Br-3-X-closo-2,1-MoCB(10)H(10)] (X = Br (7), I
      (8)), the B-NMe(3) bond is replaced by B-X. In contrast, treatment of 2 with I(2)
      and cyclo-1,4-S(2)(CH(2))(4) in CH(2)Cl(2) results in oxidative substitution of
      the cluster and retention of the NMe(3) group, giving [2,2,2-(CO)(3)-2-I-3-NMe(3)
      6-[cyclo-1,4-S(2)(CH(2))(4)]-closo-2,1-MoCB(10)H(9)] (9). The unique structural
      features of the new compounds were confirmed by single-crystal X-ray diffraction
      studies upon 6, 7, 9 and 10.

PMID- 12054998
TI  - High-nuclearity sulfide-rich molybdenum[bond]iron[bond]sulfur clusters:
      reevaluation and extension.
AB  - High-nuclearity Mo[bond]Fe[bond]S clusters are of interest as potential synthetic
      precursors to the MoFe(7)S(9) cofactor cluster of nitrogenase. In this context,
      the synthesis and properties of previously reported but sparsely described
      trinuclear [(edt)(2)M(2)FeS(6)](3-) (M = Mo (2), W (3)) and hexanuclear
      [(edt)(2)Mo(2)Fe(4)S(9)](4-) (4, edt = ethane-1,2-dithiolate; Zhang, Z.; et al.
      Kexue Tongbao 1987, 32, 1405) have been reexamined and extended. More accurate
      structures of 2-4 that confirm earlier findings have been determined. Detailed
      preparations (not previously available) are given for 2 and 3, whose structures
      exhibit the C(2) arrangement [[(edt)M(S)(mu(2)-S)(2)](2)Fe(III)](3-) with square
      pyramidal Mo(V) and tetrahedral Fe(III). Oxidation states follow from (57)Fe
      Mossbauer parameters and an S = (3)/(2) ground state from the EPR spectrum. The
      assembly system 2/3FeCl(3)/3Li(2)S/nNaSEt in methanol/acetonitrile (n = 4)
      affords (R(4)N)(4)[4] (R = Et, Bu; 70-80%). The structure of 4 contains the
      [Mo(2)Fe(4)(mu(2)-S)(6)(mu(3)-S)(2)(mu(4)-S)](0) core, with the same bridging
      pattern as the [Fe(6)S(9)](2-) core of [Fe(6)S(9)(SR)(2)](4-) (1), in overall
      C(2v) symmetry. Cluster 4 supports a reversible three-member electron transfer
      series 4-/3-/2- with E(1/2) = -0.76 and -0.30 V in Me(2)SO. Oxidation of
      (Et(4)N)(4)[4] in DMF with 1 equiv of tropylium ion gives
      [(edt)(2)Mo(2)Fe(4)S(9)](3-) (5) isolated as (Et(4)N)(3)[5].2DMF (75%).
      Alternatively, the assembly system (n = 3) gives the oxidized cluster directly as
      (Bu(4)N)(3)[5] (53%). Treatment of 5 with 1 equiv of [Cp(2)Fe](1+) in DMF did not
      result in one-electron oxidation but instead produced heptanuclear
      [(edt)(2)Mo(2)Fe(5)S(11)](3-) (6), isolated as the Bu(4)N(+)salt (38%). Cluster 6
      features the previously unknown core Mo(2)Fe(5)(mu(2)-S)(7)(mu(3)-S)(4) in
      molecular C(2) symmetry. In 4-6, the (edt)MoS(3) sites are distorted trigonal
      bipramidal and the FeS(4) sites are distorted tetrahedral with all sulfide
      ligands bridging. Mossbauer spectroscopic data for 2 and 4-6 are reported; (mean)
      iron oxidation states increase in the order 4 < 5 approximately 1 < 6
      approximately 2. Redox and spectroscopic data attributed earlier to clusters 2
      and 4 are largely in disagreement with those determined in this work. The only
      iron and molybdenum[bond]iron clusters with the same sulfide content as the
      iron[bond]molybdenum cofactor of nitrogenase are [Fe(6)S(9)(SR)(2)](4-) and
      [(edt)(2)Mo(2)Fe(4)S(9)](3-)(,4-).

PMID- 12055000
TI  - Synthesis and crystal structures of (fulvalene)W(2)(SH)(2)(CO)(6),
      (fulvalene)W(2)(mu-S(2))(CO)(6), and (fulvalene)W(2)(mu-S)(CO)(6): low valent
      tungsten carbonyl sulfide and disulfide complexes stabilized by the bridging
      fulvalene ligand.
AB  - Reaction of FvW(2)(H)(2)(CO)(6) with 2/8S(8) in THF results in rapid and
      quantitative formation of FvW(2)(SH)(2)(CO)(6). The crystal structure of this
      complex is reported and shows that the two tungsten-hydrosulfide groups are on
      opposite faces of the fulvalene ligand in an anti configuration. Nevertheless,
      treatment of FvW(2)(SH)(2)(CO)(6) (1) with PhN[double bond]NPh produces FvW(2)(mu
      S(2))(CO)(6) (2) and Ph(H)NN(H)Ph. The crystal structure of the bridging
      disulfide, which cocrystallizes with 1 in a 2:1 ratio, is also described.
      Exposure of 2 equiv of *CrCp*(CO)(3) to 1 effects similar H atom transfers
      yielding 2 HCrCp*(CO)(3) and 2. Attempts to obtain crystals of the latter from
      solutions derived from this reaction mixture furnished a third product, FvW(2)(mu
      S)(CO)(6) (3), which was analyzed crystallographically. The enthalpy of sulfur
      atom insertion into FvW(2)(H)(2)(CO)(6), yielding 1, has been measured by
      solution calorimetry.

PMID- 12055001
TI  - Diverse evolution of [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu
      S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 2, 3) metalloligands in CH(2)Cl(2).
AB  - The nucleophilicity of the [Pt(2)S(2)] core in [[Ph(2)P(CH(2))(n)PPh(2)]Pt(mu
      S)(2)Pt[Ph(2)P(CH(2))(n)PPh(2)]] (n = 3, dppp (1); n = 2, dppe (2))
      metalloligands toward the CH(2)Cl(2) solvent has been thoroughly studied. Complex
      1, which has been obtained and characterized by X-ray diffraction, is
      structurally related to 2 and consists of dinuclear molecules with a hinged
      [Pt(2)S(2)] central ring. The reaction of 1 and 2 with CH(2)Cl(2) has been
      followed by means of (31)P, (1)H, and (13)C NMR, electrospray ionization mass
      spectrometry, and X-ray data. Although both reactions proceed at different rates,
      the first steps are common and lead to a mixture of the corresponding mononuclear
      complexes [Pt[Ph(2)P(CH(2))(n)PPh(2)](S(2)CH(2))], n = 3 (7), 2 (8), and
      [Pt[Ph(2)P(CH(2))(n)PPh(2)]Cl(2)], n = 3 (9), 2 (10). Theoretical calculations
      give support to the proposed pathway for the disintegration process of the
      [Pt(2)S(2)] ring. Only in the case of 1, the reaction proceeds further yielding
      [Pt(2)(dppp)(2)[mu-(SCH(2)SCH(2)S)-S,S']]Cl(2) (11). To confirm the sequence of
      the reactions leading from 1 and 2 to the final products 9 and 11 or 8 and 10,
      respectively, complexes 7, 8, and 11 have been synthesized and structurally
      characterized. Additional experiments have allowed elucidation of the reaction
      mechanism involved from 7 to 11, and thus, the origin of the CH(2) groups that
      participate in the expansion of the (SCH(2)S)(2-) ligand in 7 to afford the
      bridging (SCH(2)SCH(2)S)(2-) ligand in 11 has been established. The X-ray
      structure of 11 is totally unprecedented and consists of a hinged [(dppp)Pt(mu
      S)(2)Pt(dppp)] core capped by a CH(2)SCH(2) fragment.

PMID- 12055002
TI  - Magnetic molecular conductors based on BETS molecules and divalent magnetic
      anions [BETS = bis(ethylenedithio)tetraselenafulvalene].
AB  - Several conducting salts based on BETS [where BETS =
      bis(ethylenedithio)tetraselenafulvalene] molecules and divalent magnetic anions
      such as the (CoCl(4))(2-), (CoBr(4))(2-), and (MnBr(4))(2-) were prepared.
      Electrocrystallization by using the (CoCl(4))(2-) anion gave two kinds of
      crystals. Block-shaped crystals were cleared to be (BETS)(2)CoCl(4), which is an
      insulator with the high-spin state of cobalt 3d spin. On the other hand, the X
      ray crystal structure analysis of a plate-shaped crystal of the (CoCl(4))(2-)
      salt revealed the system to be kappa-(BETS)(4)CoCl(4)(EtOH), which is metallic
      down to 0.7 K. The electronic band structure calculation gave a typical two
      dimensional cylindrical Fermi surface. However, there is only very weak
      antiferromagnetic interaction between the S = 3/2 cobalt 3d spins because of its
      anion-solvent-intermingled layer structure. On the other hand, the
      electrocrystallization by using the (MnBr(4))(2-) anion yielded the plate-shaped
      black crystals of the (MnBr(4))(2-) salt. Crystal structure analysis of the
      (MnBr(4))(2-) salt showed that the salt is theta;-(BETS)(4)MnBr(4)(EtOH)(2) with
      alternating donor and anion-solvent mixed layers. The stacking direction in one
      donor layer is perpendicular to those of the neighboring layers. The electrical
      and magnetic properties of the theta;-(BETS)(4)MnBr(4)(EtOH)(2) salt showed the
      metallic behavior down to approximately 30 K and the paramagnetism of the high
      spin manganese 3d spins. Band structure calculation of this salt gave an
      elliptical cylindrical Fermi surface. Because the Fermi surfaces of the adjacent
      donor layers are rotated to each other by 90 degrees, the theta
      (BETS)(4)MnBr(4)(EtOH)(2) salt becomes a two-dimensionally isotropic metal.

PMID- 12055003
TI  - Study of pH-dependent zinc(II)-carboxamide interactions by zinc(II)-carboxamide
      appended cyclen complexes (cyclen = 1,4,7,10-tetraazacyclododecane).
AB  - To elucidate intrinsic recognition of carboxamides by zinc(II) in carbonic
      anhydrase (CA) (as inhibitors) and carboxypeptidase A (CPA) (as substrates), a
      new series of Zn(2+)-carboxamide-appended cyclen complexes have been synthesized
      and characterized (cyclen = 1,4,7,10-tetraazacyclododecane). Two types of Zn(2+)
      carboxamide interactions have been found. In the first case represented by a
      zinc(II) complex of carbamoylmethyl-1,4,7,10-tetraazacyclododecane (L(1)), the
      amide oxygen binds to zinc(II) at slightly acidic pH (to form ZnL(1)), and the
      deprotonated amide N(-) binds to zinc(II) at alkaline pH (to form ZnH(-1)L(1))
      with pK(a) = 8.59 at 25 degrees C and I = 0.1 (NaNO(3)), as determined by
      potentiometric pH titrations, infrared spectral changes, and (13)C and (1)H NMR
      titrations. The X-ray crystal structure of ZnH(-1)L(3) (where L(3) = N-(4
      nitrophenyl)carbamoylmethyl cyclen, pK(a) = 7.01 for ZnL(3) <==> ZnH(-1)L(3))
      proved that the zinc(II) binds to the amidate N(-) (Zn-N(-) distance of 1.974(3)
      A) along with the four nitrogen atoms of cyclen (average Zn-N distance 2.136 A).
      Crystal data: monoclinic, space group P2(1)/n (No. 14) with a = 10.838(1) A, b =
      17.210(2) A, c = 12.113(2) A, b = 107.38(1) degrees, V = 2156.2(5) A(3), Z = 4, R
      = 0.042, and R(w) = 0.038. These model studies provide the first chemical support
      that carboxamides are CA(-) inhibitors by occupying the active Zn(2+) site both
      in acidic and alkaline pH to prevent the occurrence of the catalytically active
      Zn(2+)-OH(-) species. In the second case represented by a zinc(II) complex of 1
      (N-acetyl)aminoethylcyclen, ZnL(6), the pendant amide oxygen had little
      interaction with zinc(II) at acidic pH. At alkaline pH, the monodeprotonation
      yielded a zinc(II)-bound hydroxide species ZnL(6)(OH(-)) (pK(a) = 7.64) with the
      amide pendant remaining intact. The ZnL(6)(OH(-)) species showed the same
      nucleophilic activity as Zn(2+)-cyclen-OH(-). The second case may mimic the
      Zn(2+)-OH(-) mechanism of CPA, where the nucleophilic Zn(2+)-OH(-) species does
      not act as a base to deprotonate a proximate amide.

PMID- 12055004
TI  - Synthesis, characterization, and properties of three europium 2-propoxides:
      [Eu(4)(OPr(i))(10)(HOPr(i))(3)]*2HOPr(i), Eu(5)O(OPr(i))(13), and
      EuAl(3)(OPr(i))(12).
AB  - The reaction of Eu metal with HOPr(i)/toluene solutions yielded the mixed
      Eu(2+)/Eu(3+) alkoxide [Eu(4)(OPr(i))(10)(HOPr(i))(3)] x 2HOPr(i) (1), in
      contrast to the other lanthanide metals, which exclusively yield trivalent
      lanthanide ions in the alkoxides formed. Metathesis between EuCl(3) and 3KOPr(i)
      and stoichiometric hydrolysis yielded the square-pyramidal Eu(5)O(OPr(i))(13)
      (2), and metathesis with EuCl(3) and 3KAl(OPr(i))(4) gave EuAl(3)(OPr(i))(12)
      (3). The structures of these compounds were determined by single-crystal X-ray
      diffraction. IR spectroscopic studies showed that the solid-state molecular
      structure of the three alkoxides remained close to intact in solution. Further
      characterizations were made with UV-vis spectroscopy, differential scanning
      calorimetry, and solubility studies. It was also found that 1 can be converted to
      2 by oxidation with dioxygen, but 2 was not reduced by Eu metal to 1. The
      reactions of 2 and 1 with Al(4)(OPr(i))(12) in toluene/HOPr(i) solvent were
      studied by IR and UV-vis spectroscopy; 2 reacted completely to form 3 in 2 h at
      75 degrees C, while 1 reacted to yield 3 and other unidentified Eu(2+) containing
      product(s) in the same time.

PMID- 12055005
TI  - Investigation of silver salt metathesis: preparation of cationic germanium(II)
      and Tin(II) complexes, and silver adducts containing unsupported silver-germanium
      and silver-tin bonds.
AB  - Syntheses of halide derivatives of germanium(II) and tin(II) aminotroponiminate
      (ATI) complexes and their silver salt metathesis reactions have been
      investigated. The treatment of GeCl(2) x (1,4-dioxane), SnCl(2), or SnI(2) with
      [(n-Pr)(2)ATI]Li in a 1:1 molar ratio affords the corresponding germanium(II) or
      tin(II) halide complex [(n-Pr)(2)ATI]MX (where [(n-Pr)(2)ATI](-) = N-(n-propyl)-2
      (n-propylamino)troponiminate; M = Ge or Sn; X = Cl or I). As usually expected,
      [(n-Pr)(2)ATI]GeCl and [(n-Pr)(2)ATI]SnCl undergo rapid metathesis with
      CF(3)SO(3)Ag, leading to trifluoromethanesulfonate salts, [[(n
      Pr)(2)ATI]Ge][SO(3)CF(3)] and [[(n-Pr)(2)ATI]Sn][SO(3)CF(3)], and silver
      chloride. However, when the silver source [HB(3,5-(CF(3))(2)Pz)(3)]Ag(eta(2)
      toluene) is used, rather than undergoing metathesis, very stable 1:1 adducts
      [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Ge(Cl)[(n-Pr)(2)ATI] and [HB(3,5
      (CF(3))(2)Pz)(3)]Ag<--Sn(Cl)[(n-Pr)(2)ATI] are formed (where [HB(3,5
      (CF(3))(2)Pz)(3)](-) = hydrotris(3,5-bis(trifluoromethyl)pyrazolyl)borate). The
      use of the iodide derivative [(n-Pr)(2)ATI]SnI did not change the outcome either.
      All new compounds have been characterized by multinuclear NMR spectroscopy and X
      ray crystallography. The Ag-Ge and Ag-Sn bond distances of [HB(3,5
      (CF(3))(2)Pz)(3)]Ag<-- Ge(Cl)[(n-Pr)(2)ATI], [HB(3,5-(CF(3))(2)Pz)(3)]Ag<-
      Sn(Cl)[(n-Pr)(2)ATI], and [HB(3,5-(CF(3))(2)Pz)(3)]Ag<--Sn(I)[(n-Pr)(2)ATI] are
      2.4142(6), 2.5863(6), and 2.5880(10) A, respectively. A convenient route to [(n
      Pr)(2)ATI]H is also reported.

PMID- 12055006
TI  - Cooperative ligation, back-bonding, and possible pyridine-pyridine interactions
      in tetrapyridine-vanadium(II): a visible and X-ray spectroscopic study.
AB  - The binding of pyridine by V(II) in aqueous solution shows evidence for the late
      onset of cooperativity. The K(1) governing formation of [V(py)](2+) (lambda(max)
      = 404 nm, epsilon(max) = 1.43 +/- 0.3 M(-1) cm(-1)) was determined
      spectrophotometrically to be 11.0 +/- 0.3 M(-)(1), while K(1) for isonicotinamide
      was found to be 5.0 +/- 0.1 M(-1). These values are in the low range for 3d M(2+)
      ions and indicate that V(II).py back-bonding is not significant in the formation
      of the 1:1 complex. Titration of 10.5 mM V(II) with pyridine in aqueous solution
      showed an absorption plateau at about 1 M added pyridine, indicating a reaction
      terminus. Vanadium K-edge EXAFS analysis of 63 mM V(II) in 2 M pyridine solution
      revealed six first-shell N/O ligands at 2.14 A and 4 +/- 1 pyridine ligands per
      V(II). UV/vis absorption spectroscopy indicated that the same terminal V(II)
      species was present in both experiments. Model calculations showed that in the
      absence of back-bonding only 2.0 +/- 0.2 and 2.4 +/- 0.2 pyridine ligands would
      be present, respectively. Cooperativity in multistage binding of pyridine by
      [V(aq)](2+) is thus indicated. XAS K-edge spectroscopy of crystalline
      [V(O(3)SCF(3))(2)(py)(4)] and of V(II) in 2 M pyridine solution each exhibited
      the analogous 1s --> (5)E(g) and 1s --> (5)T(2g) transitions, at 5465.5 and
      5467.5 eV, and 5465.2 and 5467.4 eV, respectively, consistent with the EXAFS
      analysis. In contrast, [V(py)(6)](PF(6))(2) and [V(H(2)O)(6)]SO(4) show four 1s -
      > 3d XAS transitions suggestive of a Jahn-Teller distorted excited state.
      Comparison of the M(II)[bond]N(py) bond lengths in V(II) and Fe(II)
      tetrapyridines shows that the V(II)[bond]N(py) distances are about 0.06 A shorter
      than predicted from ionic radii. For [VX(2)(R-py)(4)] (X = Cl(-), CF(3)SO(3)(-);
      R = 4-Et, H, 3-EtOOC), the E(1/2) values of the V(II)/V(III) couples correlate
      linearly with the Hammett sigma values of the R group. These findings indicate
      that pi back-bonding is important in [V(py)(4)](2+) even though absent in
      [V(py)](2+). The paramagnetism of [V(O(3)SCF(3))(2)(py)(4)] in CHCl(3), 3.8 +/-
      0.2 mu(B), revealed that the onset of back-bonding is not accompanied by a spin
      change. Analysis of the geometries of V(II) and Fe(II) tetrapyridines indicates
      that the ubiquitous propeller motif accompanying tetrapyridine ligation may be
      due to eight dipole interactions arising from the juxtaposed C-H edges and pi
      clouds of adjoining ligands, worth about -6 kJ each. However, this is not the
      source of the cooperativity in the binding of multiple pyridines by V(II) because
      the same interactions are present in the Fe(II)-tetrapyridines, which do not show
      cooperative ligand binding. Cooperativity in the binding of pyridine by V(II) is
      then assigned by default to V(II)-pyridine back-bonding, which emerges only after
      the first pyridine is bound.

PMID- 12055007
TI  - A mechanistic investigation of oxidative addition of methyl iodide to
      [Tp*Rh(CO)(L)].
AB  - Reaction of methyl iodide with square planar [kappa(2)-Tp*Rh(CO)(PMe(3))] 1a (Tp*
      = HB(3,5-Me(2)pz)(3)) at room temperature affords [kappa(3)
      Tp*Rh(CO)(PMe(3))(Me)]I 2a, which was fully characterized by spectroscopy and X
      ray crystallography. The pseudooctahedral geometry of cationic 2a, which contains
      a kappa(3)-coordinated Tp* ligand, indicates a reaction mechanism in which
      nucleophilic attack by Rh on MeI is accompanied by coordination of the pendant
      pyrazolyl group. In solution 2a transforms slowly into a neutral (acetyl)(iodo)
      rhodium complex [kappa(3)-Tp*Rh(PMe(3))(COMe)I] 3a, for which an X-ray crystal
      structure is also reported. Kinetic studies on the reactions of [kappa(2)
      Tp*Rh(CO)(L)] (L = PMe(3), PMe(2)Ph, PMePh(2), PPh(3), CO)] with MeI show second
      order behavior with large negative activation entropies, consistent with an S(N)2
      mechanism. The second-order rate constants correlate well with phosphine
      basicity. For L = CO, reaction with MeI gives an acetyl complex, [kappa(3)
      Tp*Rh(CO)(COMe)I]. The bis(pyrazolyl)borate complexes [kappa(2)-Bp*Rh(CO)(L)] (L
      = PPh(3), CO) are much less reactive toward MeI than the Tp* analogues,
      indicating the importance of the third pyrazolyl group and the accessibility of a
      kappa(3) coordination mode. The results strengthen the evidence in favor of an
      S(N)2 mechanism for oxidative addition of MeI to square planar d(8) transition
      metal complexes.

PMID- 12055008
TI  - Molten-globule and other conformational forms of zinc cytochrome C. Effect of
      partial and complete unfolding of the protein on its electron-transfer
      reactivity.
AB  - To test the effect of protein conformation on reactivity, we use laser flash
      photolysis to compare the electron-transfer properties of the triplet state of
      zinc-substituted cytochrome c, designated (3)Zncyt, in the folded forms at low
      (F(low)) and high (F(high)) ionic strength, molten-globule (MG) form, and the
      forms unfolded by acid (U(acid)) and urea (U(urea)) toward the following four
      oxidative quenchers: Fe(CN)(6)(3-), Co(acac)(3), Co(phen)(3)(3+), and iron(III)
      cytochrome c. We characterize the conformational forms of Zncyt on the basis of
      the far-UV circular dichroism, Soret absorption, and rate constant for natural
      decay of the triplet state. This rate constant in the absence of quencher
      increases in the order F(high) < F(low) < MG < U(acid) < U(urea) because the
      exposure of porphyrin to solvent increases as Zncyt unfolds. Bimolecular rate
      constants for the reaction of (3)Zncyt with the four quenchers show significant
      effects on reactivity of electrostatic interactions and porphyrin exposure to
      solvent. This rate constant at the ionic strength of 20 mM increases upon
      unfolding by urea and acid, respectively, as follows: 1340-fold and 466-fold when
      the quencher is Co(phen)(3)(3+) and 168-fold and 36-fold when the quencher is
      cyt(III). To compare reactivity of (3)Zncyt in the F(low), F(high), MG, U(acid),
      and U(urea) forms without complicating effects of electrostatic interactions, we
      used the electroneutral quencher Co(acac)(3). Indeed, reactivity of folded
      (3)Zncyt with Co(acac)(3) was independent of ionic strength. Reactivity of
      (3)Zncyt with Co(acac)(3) upon partial and complete unfolding increases 10-fold,
      54-fold, and 64-fold in the molten-globule, urea-unfolded, and acid-unfolded
      forms.

PMID- 12055009
TI  - Hydrothermal synthesis, structures, and magnetic properties of three novel 5
      aminoisophthalic acid ligand bridged transition metal cation polymers.
AB  - Three novel 5-aminoisophthalic acid (AIP) bridged polymers
      [Co(C(8)NH(5)O(4))(H(2)O)](n)() (1), [Ni(C(8)NH(5)O(4))(H(2)O)(2)](n)() (2), and
      [Zn(C(8)NH(5)O(4))(H(2)O)](n)() (3) were synthesized by hydrothermal reactions
      and characterized by IR, Raman, elemental analysis, ESR, and magnetic
      measurements. X-ray single-crystal analyses were carried out for
      [Co(C(8)NH(5)O(4))(H(2)O)](n)() (1), which crystallizes in the triclinic system,
      space group P1 macro, with a = 6.477(1) A, b = 7.130(1) A, c = 9.826(2) A, alpha
      = 108.9(1) degrees, beta = 93.97(3) degrees, gamma = 98.82(3) degrees, and Z = 2;
      for [Ni(C(8)NH(5)O(4))(H(2)O)(2)](n)() (2), in the triclinic system, space group
      P1 macro, a = 6.425(1) A, b = 8.115(2) A, c = 10.146(2) A, alpha = 113.09(3)(o),
      beta = 99.64(3)(o), gamma = 98.90(3)(o), and Z = 2; and for
      [Zn(C(8)NH(5)O(4))(H(2)O)](n)() (3), in the monoclinic system, space group
      P2(1)/n, a = 9.044(1) A, b = 8.264(1) A, c = 11.646(1) A, beta = 100.77(1)
      degrees, and Z = 4. The single X-ray diffraction studies reveal that 1 consists
      of an infinite honeycomb layer formed by four crystallographically independent
      motifs packed alternatively together; 2 consists of an infinite neutral railroad
      like linear polymer, and 3 consists of infinite layers of alternating four
      coordinated Zn(II) cations and AIP ligands. Finally, they are all packed into
      beautiful three-dimensional frameworks through complicated hydrogen bonding.
      Antiferromagnetic and ferromagnetic behaviors were observed for 1 and 2 from the
      magnetic measurements.

PMID- 12055010
TI  - Magnetic ordering in the rare earth molecule-based magnets, Ln(TCNE)(3) (Ln = Gd,
      Dy; TCNE = tetracyanoethylene).
AB  - The reaction of LnI(3) x xMeCN (Ln = Gd, Dy) and TCNE (tetracyanoethylene) in
      acetonitrile forms Ln(2)[C(4)(CN)(8)](3) x xMeCN. These paramagnetic light
      colored solids contain the S = 0 octacyanobutandiide dianion, [C(4)(CN)(8)](2-),
      which upon desolvation of these products forms dark green Ln(TCNE)(3). In these
      compounds the central C[bond]C sigma bond in [C(4)(CN)(8)](2-) is broken, re
      forming S = 1/2 [TCNE]*(-). as evidenced by the color change and the infrared
      spectra. Ln(TCNE)(3) exhibit coupling between Ln(3+) and [TCNE]*(-) and
      magnetically order as ferrimagnets at 8.5 (Dy) and 3.5 (Gd) K.

PMID- 12055011
TI  - Synthesis and structural characterization of Cu(I) and Ni(II) complexes that
      contain the bis[2-(diphenylphosphino)phenyl]ether ligand. Novel emission
      properties for the Cu(I) species.
AB  - The pseudotetrahedral complexes [Cu(NN)(DPEphos)]BF(4), where DPEphos = bis[2
      (diphenylphosphino)phenyl]ether and NN = 1,10-phenanthroline (1), 2,9-dimethyl
      1,10-phenanthroline (2), 2,9-di-n-butylphenanthroline (3), or two
      dimethylcyanamides (4), and NiCl(2)(DPEphos) (5) have been synthesized and
      structurally characterized by X-ray crystallography and their solution properties
      examined by use of a combination of cyclic voltammetry, NMR spectroscopy, and
      electronic absorption spectroscopy. Complexes 1-4 possess a reversible
      Cu(II)/Cu(I) couple at potentials upward of +1.2 V versus Ag/AgCl. Compounds 1-3
      exhibit extraordinary photophysical properties. In room-temperature
      dichloromethane solution, the charge-transfer excited state of the dmp (dbp)
      derivative exhibits an emission quantum yield of 0.15 (0.16) and an excited-state
      lifetime of 14.3 mus (16.1 mus). Coordinating solvents quench the charge-transfer
      emission to a degree, but the photoexcited dmp complex 2 retains a lifetime of
      over a microsecond in acetone, methanol, and acetonitrile.

PMID- 12055012
TI  - Two chiral coordination polymers: preparation and X-ray structures of mono(4
      sulfo-L-phenylalanine)(diaqua) zinc(II) and copper(II) complexes.

PMID- 12055013
TI  - Outcome of major cardiac injuries at a Canadian trauma center.
AB  - BACKGROUND: Canadian trauma units have relatively little experience with major
      cardiac trauma (disruption of a cardiac chamber) so injury outcome may not be
      comparable to that reported from other countries. We compared our outcomes to
      those of other centers. METHODS: Records of patients suffering major cardiac
      trauma over a nine-year period were reviewed. Factors predictive of outcome were
      analyzed. RESULTS: Twenty-seven patients (11 blunt and 16 penetrating) with major
      cardiac trauma were evaluated. Injury severity scores (ISS) were similar for
      blunt (49.6 +/- 16.6) and penetrating (39.5 +/- 21.6, p = 0.20) injuries. Five of
      11 blunt trauma patients, and 9 of 16 penetrating trauma patients, had detectable
      vital signs on hospital arrival (p = 0.43). Ten patients underwent emergency
      department thoracotomy and 11 patients had cardiac repair in the operating
      theatre. Eleven patients survived and 16 died. Survivors had a lower ISS (33.7 +/
      15.4) than non-survivors (50.4 +/- 20.4; p = 0.03). Two of 11 blunt trauma
      patients and 9 of 16 penetrating trauma patients survived (p = 0.06). Eleven of
      14 patients with detectable vital signs survived; all 13 without detectable vital
      signs died (p = 0.00003). Ten of eleven patients treated in the operating theatre
      survived, while only one of the other 16 patients survived (p = 0.00002).
      CONCLUSIONS: Patients with major cardiac injuries and detectable vital signs on
      hospital arrival can be salvaged by prompt surgical intervention in the operating
      theatre. Major cardiac injuries are infrequently encountered at our center but
      patient survival is comparable to that reported from trauma units in other
      countries.

PMID- 12055017
TI  - The subchronic oral toxicity of ethane, 1,2-bis(pentabromophenyl) (Saytex 8010)
      in rats.
AB  - Ethane, 1,2-bis(pentabromophenyl) (EBP; CAS no. 8452-53-9) dose levels of 0, 100,
      320 and 1000 mg/kg/day administered to rats by gavage in corn oil for 90
      consecutive days produced no compound-related clinical signs of systemic
      toxicity, ocular lesions, or alterations in urinalysis, clinical chemistry, and
      hematology values in the treated or recovery groups. No biologically or
      toxicologically significant differences were observed in body weights, body
      weight gains, and food consumption. Statistically significant differences were
      found between control and high-dose animals in mean absolute or relative liver
      weights. Histomorphological evaluation showed in male rats low-grade liver
      changes consisting of minimal to slight hepatocellular vacuolation (high-dose
      males) and minimal to slight centrilobular hepatocytomegaly (high- and possibly
      mid-dose males). These changes had resolved by the end of the 28-day recovery
      period. No treatment-related changes were found in the livers of female rats. No
      treatment-related histomorphologic changes were present in any of the other
      tissues examined in either sex, except for evidence of aspirated test article in
      individual rats. The 90-day EBP no-adverse-effect level in the rat was > or =
      1000 mg/kg/day, and was consistent with that of the preceding 28-day study (no
      effect level > or = 1250 mg/kg/day). EBP's lack of toxicity is likely related to
      poor bioavailability due to its high molecular weight and low solubility.

PMID- 12055018
TI  - Evaluation of the carcinogenic potential of insulin glargine (LANTUS) in rats and
      mice.
AB  - Insulin glargine (LANTUS) is a new, long-acting insulin analogue with a stable
      profile of action. The purpose of these studies was to evaluate the carcinogenic
      potential of insulin glargine in rats and mice. General toxicity studies were
      conducted in NMRI mice (3 months' duration) and rats (Wistar rats in the 3- and 6
      month studies and Sprague-Dawley rats in the 12-month study) to determine the
      optimal dose of insulin glargine for long-term carcinogenicity studies. Based on
      these results, groups of Sprague-Dawley rats or NMRI mice (50 male, 50 female)
      received a daily subcutaneous dose of 2, 5, or 12.5 IU/kg of insulin glargine or
      12.5 (mice) or 5 IU/kg (rats) of the reference insulin (NPH insulin) in a
      lifetime study. Similarly treated control and vehicle-control animals received
      isotonic sodium chloride (NaCl) solution or the vehicle solution, respectively.
      In mice, the mortality rate was comparable between all groups. In rats, the
      mortality rate compared with the NaCl control was significantly increased in the
      following groups: males treated with the vehicle control, all insulin glargine
      and NPH insulin groups, and in females in the high-dose insulin glargine and NPH
      insulin groups. There was no difference in the incidence of mammary tumors
      reported in both mice and rats when comparing the insulin glargine groups with
      the NaCl, vehicle-control, or the NPH insulin groups. In rats and mice, the
      distribution of subcutaneous malignant fibrous histiocytomas found at the
      injection site were not dose-dependent. These lesions are a rodent-specific event
      and were related to chronic tissue irritation and inflammation. In rats, neuronal
      necrosis of the cerebrum was attributed to persistent repeated episodes of
      hypoglycemia induced by high doses of insulin. In these studies, there were no
      neoplastic findings to indicate that insulin glargine had a systemic carcinogenic
      potential in mice or rats.

PMID- 12055019
TI  - Evaluation of the reproductive toxicity and embryotoxicity of insulin glargine
      (LANTUS) in rats and rabbits.
AB  - Insulin glargine (LANTUS) is a new insulin analog that has a prolonged duration
      of action with no pronounced peak of activity, rendering it an ideal basal
      insulin for the treatment of diabetes. The aim of these studies was to assess the
      reproductive and embryotoxicity of insulin glargine. Reproductive toxicity was
      assessed in 25 male and 25 female Wistar rats per group treated with a daily
      subcutaneous injection of control; 1 IU/kg, 3 IU/kg, and 10 IU/kg insulin
      glargine; or 3 IU/kg NPH insulin in the premating and mating periods, and
      throughout pregnancy and lactation in the females. Embryotoxicity was assessed in
      20 female rats per group injected with daily subcutaneous doses of control; 2
      IU/kg, 6.3 IU/kg, and 20 IU/kg insulin glargine; or 6.3 IU/kg NPH insulin from
      the 7th to 18th day of pregnancy. Embryotoxicity was also assessed in 20 female
      rabbits per group treated with 0 IU/kg, 0.5 IU/kg, 1 IU/kg, and 2 IU/kg insulin
      glargine, or 1 IU/kg NPH insulin from the 6th to 18th day of pregnancy. The data
      demonstrated that, with the exception of toxicologic effects induced by
      hypoglycemia in response to high doses of insulin glargine and NPH insulin
      (including the premature dropout of female rats in the reproductive toxicity
      study, and increased incidence of abortions, early intrauterine deaths, and
      single anomalies in the rabbit embryotoxicity study), insulin glargine had no
      effects on reproduction, embryofetal development, and postnatal development in
      rats. Maternal and embryofetal toxicity in rabbits treated with middle and high
      doses of insulin glargine was related to the hypoglycemic effect of insulin.

PMID- 12055020
TI  - The blockade of mineralocorticoid hormone signaling provokes dramatic
      teratogenesis in cultured rat embryos.
AB  - Although the administration of adrenocortical hormones to pregnant rats provokes
      only limited effect on the growth and development of the fetus, the direct
      influence of these steroids on cultured embryos has never been studied. The
      disruption of cell signaling by ZK 91587, which specifically occupies the
      mineralocorticoid receptor, resulted within 2 days in significant and pronounced
      adverse effects on the total length, the somite number, the embryo curvature, the
      communication between vitelline and umbilical blood vessels in the allantoid, and
      the vascularization of the vitelline sac, in 244-hour Wistar rat embryos in
      culture. The average score of 16 organs declined in a dose-dependent manner,
      following exposure to ZK 91587, and this was totally reversed by 10 microM
      aldosterone which, by itself, did not at all influence the embryonic development.
      The organogenesis was inhibited in the order: hind limb > fore limb > optic stalk
      > brain > olfactory pit > otic vesicle. ZK 91587 was completely ineffective in
      embryos that had attained the age of 260 hours. Similar, but less dramatic,
      results were obtained with the mineralocorticoid antagonist RU 26752, and with
      the antiglucocorticoid RU 38486. Sprague-Dawley rat embryos responded in a manner
      similar to the Wistar conceptuses. Thus, steroid receptor-mediated cell signaling
      is of critical importance to the growth and development of cultured rat embryos,
      which form a new model system to unravel adrenocortical hormone action.

PMID- 12055021
TI  - Vicine and convicine in common vetch (Vicia sativa) seeds enhance beta
      cyanoalanine toxicity in male broiler chicks.
AB  - Two studies were conducted to investigate the effects of feeding raw and water
      soaked vetch seeds to male broiler chicks on performance, organ weights, and
      blood parameters. Intact and ground vetch seeds were soaked in water (1:5) at
      room temperature for 24 hours (study 1), and (1:10) at 40 degrees C for 24, 48,
      and 72 hours, with water change every 12 hours (study 2). In study 1, untreated
      vetch contained, on dry matter basis, 0.530%, 0.731%, and 0.081% total beta
      cyanoalanine (BCA), vicine, and convicine, respectively. Toxins were not
      appreciably reduced in soaked intact and ground vetch. Diets containing
      untreated, soaked intact, and soaked ground vetch, each at 0%, 20%, 40%, and 60%,
      were fed to 7-day-old male broilers until onset of neurotoxicity symptoms.
      Survival time was not only decreased by BCA level but also by those of vicine and
      convicine (p <.05). In study 2, 60% of untreated or treated vetch seeds were
      incorporated in chick diets. Although untreated vetch used in this study
      contained 32% less BCA but 8% and 81% more vicine and convicine, respectively,
      yet, the chicks on 60% untreated vetch showed toxicity symptoms earlier than
      those of study 1. Soaking ground vetch for 48 hours or more reduced BCA and
      totally removed vicine and convicine. Consequently, birds on 60% ground vetch
      soaked for 48 and 72 hours survived through the starter period and had mean
      corpuscular hemoglobin concentration and organ weights comparable to those of
      control at 4 days post trial. The results indicated that "high levels" of vicine
      or convicine or both might have shortened the birds' survival time by enhancing
      the neurotoxicity induced by "lower levels" of BCA.

PMID- 12055022
TI  - Chromium toxic effect monitoring using ozonation method.
AB  - The hexavalent chromium toxicity (in vitro) to plasma, erythrocytes, and semen
      lipids was evaluated. The ozonation technique is suggested to realize the rapid
      measurements of the lipid peroxidation (LPO) by means of the double bond indexes
      (DB-index and DB(cell)-index) calculation. The obtained experimental results
      permit to conclude that it is possible to detect the chromium effect on LPO by
      ozonation. The DB-index and DB(cell)-index determination in the plasma,
      erythrocytes, and sperm can be considered as a measure of this effect. Ozonation,
      suggested in this work, can provide the useful preliminary information for
      specialists and is a quantitative, fast, inexpensive, and simple method. In view
      of these comments, we conclude that the suggested ozonation method can be
      considered as the acceptable modern technique for the chromium toxic effect
      monitoring in vitro.

PMID- 12055023
TI  - Carcinogenicity of bromodichloromethane administered in drinking water to Male
      F344/N Rats and B6C3F1 mice.
AB  - A life-time exposure study was conducted to assess the carcinogenicity of
      bromodichloromethane (BDCM) administered in the drinking water to male F344/N
      rats and B6C3F(1) mice. In mouse, the calculated mean daily BDCM concentrations
      (measured concentrations corrected for on-cage loss of chemical) were 0.06, 0.28
      and 0.49 g/l. Time-weighted water consumption of 135, 97, and 89 ml/kg/day
      resulted in mean daily doses of 8.1, 27.2, and 43.4 mg BDCM/kg/day. No changes in
      feed consumption, final body weight, or survival were observed. Kidney weights
      were significantly depressed at 27.2 and 43.4 mg BDCM/kg/day. There was no
      increase in neoplasia in the liver, kidney, spleen, testis, bladder, sections
      along the alimentary tract, excised lesions, or at any other organ site. In rat,
      the corrected mean daily BDCM concentrations were 0.06, 0.33, and 0.62 g/l. Time
      weighted water consumption of 65, 63, and 59 ml/kg/day yielded 3.9, 20.6 and 36.3
      mg BDCM/kg/day. No alterations in feed consumption, body weight gain, and
      survival were seen. Kidney weight was significantly depressed in the 36.3
      mg/kg/day treatment group. There was a significantly enhanced prevalence and
      multiplicity of hepatocellular adenomas at 3.9 mg BDCM/kg/day (15.5% and
      0.16/animal vs. 2.2% and 0.02/animal for the control). Hepatocellular carcinomas
      increased from 2.2% and 0.02/animal for the control and 3.9 mg BDCM/kg/day to
      8.3% and 0.10/animal at 20.6 mg BDCM/kg/day. The combined neoplasms were enhanced
      at 3.9 and 20.6 mg BDCM/kg/day. Liver neoplasia was depressed to the control
      value at 36.3 mg BDCM/kg. The prevalence of basophilic and clear cell, but not
      eosinophilic cells, altered foci of cells declined with increasing dose. BDCM did
      not increase cancer in the large bowel, renal tubules, or in any of the other
      tissues examined. Renal tubular hyperplasia was observed at 36.3 mg BDCM/kg
      (15.8% vs. 8.7% for the control group). Under the conditions of the study, BDCM
      in the drinking water was not carcinogenic in the male B6C3F(1) mouse, but was
      carcinogenic in the male F344/N rat based on an increased hepatocellular
      neoplasia.

PMID- 12055024
TI  - Acute toxicity of TBT and IRGAROL in Artemia salina.
AB  - A 24-hour LC(50) bioassay method was carried out to study acute toxicity of
      Tributyltin (TBT) and IRGAROL (C(11)H(19)N(5)S) in Artemia salina. Five graded
      levels of both biocides were tested. According to the range test, the doses of
      TBT were 11.6 ng x l(-1), 21.0 ng x l(-1), 37.3 ng x l(-1), 65.2 ng x l(-1), and
      116.5 ng x l(-1), and for IRGAROL were 1.0 mg x l(-1), 1.8 mg x l(-1), 3.2 mg x
      l(-1), 5.6 mg x l(-1), and 10 mg x l(-1). The determined LC(50) values were 41.41
      ng x l(-1) and 1.62 mg x l(-1) respectively. These results indicate that in this
      system TBT is acutely more toxic than IRGAROL; however, both are proven
      environmentally toxic substances.

PMID- 12055025
TI  - 9th National Retrovirus Conference: new treatments, new choices.

PMID- 12055026
TI  - Safer-sex education: evaluating effectiveness with test scores.

PMID- 12055027
TI  - Mycobacterium avium complex-associated cholecystitis in an HIV-infected woman.
AB  - Mycobacterium avium complex (MAC) is commonly associated with fever, fatigue,
      nausea, diarrhea, and cytopenias related to invasion of the intestine and bone
      marrow. Infection and clinical disease has been reported in other organs as well.
      We report the first case of cholecystitis associated with MAC infection of the
      gallbladder.

PMID- 12055028
TI  - HIV infection is a risk factor for venous thromboembolism.
AB  - The reported incidence of venous thromboembolism (VTE) in patients with human
      immunodeficiency virus (HIV) infection has ranged from 0.25 to 0.96% in clinical
      studies, but up to 17% at autopsy. A preliminary analysis at our hospital
      suggested that the frequency of VTE among HIV-positive individuals might be
      higher than previously reported. To further evaluate this issue, we performed a
      retrospective study of patients with a diagnosis of VTE and/or HIV infection
      discharged from our hospital between July 1, 1998 and June 30, 1999. A total of
      13,496 patients were discharged during the year of the study. There were 244
      patients with VTE and 362 who were HIV-positive. Ten of the 244 patients with VTE
      were HIV-positive (4.1%). The frequency of VTE among HIV-positive individuals was
      10/362 (2.8%) compared to 234/13134 (1.8%) in the non-HIV-positive group, but the
      difference is not statistically significant. However, in patients under age 50,
      the frequencies were significantly different: 10/302 (3.31%) versus 35/6594
      (0.53%), respectively (p < 0.0001). The frequency of VTE in HIV-positive patients
      less than 50 years old (3.31%) was greater than in HIV-positive patients over 50
      years of age (0/60), but the difference did not reach statistical significance.
      In contrast, in the non-HIV-positive group, VTE was significantly more frequent
      in those 50 and older compared to younger patients (3.04% versus 0.53%, p =
      0.0001). Statistical analysis indicated that the direction of association between
      age and diagnosis of VTE differed for HIV-positive patients versus non-HIV
      positive patients. Our results suggest that HIV-positive patients under age 50
      are at increased risk for VTE compared with non-HIV-positive individuals.

PMID- 12055029
TI  - Interactions of the female hormonal environment, susceptibility to viral
      infections, and disease progression.
AB  - Sex hormones influence susceptibility and disease predisposition for many genital
      tract infections. This review describes the mechanisms by which sex steroids
      affect mucosal immunity, with particular reference to human immunodeficiency
      virus (HIV) and genital herpes, and the stage-specific effects of hormonal
      contraception on human papillomavirus (HPV) infection. Estrogen's role is
      important in the early stages of several infections as it stimulates antibody-
      and cell-mediated immune responses. There is increased expression of some
      cytokines in peripheral blood and vaginal fluids during the follicular phase of
      the menstrual cycle and with use of hormonal contraception. Whether estrogen
      exerts a protective or deleterious influence depends on the infecting organism
      and stage of infection or disease. Estrogen apparently reduces susceptibility to
      primary HPV infection but in the event of persistent HPV infection, sex steroid
      hormones (estrogen and/or progesterone) are associated with progression to
      cervical cancer. It is important that these stage-specific effects are better
      described because most vaccines will try to prevent either infection or disease.
      Clinicians with patients at high risk of sexually transmitted infections,
      especially HIV, require better information on the risks associated with different
      hormonal contraceptive regimes.

PMID- 12055030
TI  - Does access to health care impact survival time after diagnosis of AIDS?
AB  - Lack of access to health care is often blamed for poor health outcomes, but this
      effect is not supported by existing HIV/AIDS literature. The authors examined the
      association between access to care and survival time after progression to AIDS,
      using survival analysis methods. This study combined data from two CDC sponsored
      studies of HIV-infected persons, a cross-sectional interview study and a
      longitudinal medical record review study. Study subjects included 752 persons who
      progressed to AIDS before December 31, 1999, and were patients at either of two
      major HIV care facilities in Detroit, MIchigan. Separate statistical models were
      used to test associations between survival time after meeting the criteria for
      AIDS and two indicators of access to health care: (1) perceived access to health
      care and (2) health care utilization patterns. Perceived access was not
      associated with survival time after AIDS, but patterns of health care utilization
      were significantly associated with survival time after AIDS (HR = 2.04, p <
      0.001). Individuals who received a greater proportion of their care in the ER had
      a worse survival prognosis than those who received more of their health care in
      an outpatient clinic setting. It is crucial that we provide HIV-infected
      populations with tools that enable them to access a regular source of health
      care.

PMID- 12055032
TI  - Change in d4T label.

PMID- 12055031
TI  - Perceptions of health care among persons living with HIV/AIDS who are not
      receiving antiretroviral medications.
AB  - Antiretroviral medications are effective at improving the health and increasing
      the survival of people living with HIV/AIDS. However, studies have shown that a
      substantial number of HIV-infected people do not receive antiretroviral
      treatments. The current study examined the physical and mental health, substance
      use, and perceptions of medical care of 163 men and 78 women living with
      HIV/AIDS. Results of a confidential survey showed that 79 (33%) were not
      currently treated for HIV. These persons did not differ from those who were
      treated in chart-abstracted CD4 cell counts, years living with HIV infection, HIV
      related symptoms, and HIV-related hospitalizations. Unlike past studies, gender
      was not found to be a factor in treatment status. However, untreated persons had
      higher chart-abstracted viral loads and were more likely to be ethnic minorities,
      have a lower level of education, greater level of depression, and greater
      pessimistic attitude. They were significantly more likely to have used alcohol,
      powder cocaine, and crack cocaine in the previous 3 months, were likely to know
      their own viral load and CD4 count, and held significantly more negative views of
      their health care and their health care providers. There were no differences
      between untreated and treated persons in their meeting the year 1999
      antiretroviral treatment guidelines that were in effect at the time of data
      collection. These results suggest that persons who are not receiving
      antiretroviral medications may be in need of mental health and substance use
      interventions and may benefit from interventions designed to engage and retain
      them in medical treatment.

PMID- 12055033
TI  - Microbicides may be ready.

PMID- 12055035
TI  - A crosslinked calcium-alginate-pectinate-cellulose acetophthalate gelisphere
      system for linear drug release.
AB  - This study proposes a novel binary crosslinked ternary multiple-unit system,
      collectively referred to as calcium-alginate-pectinate-cellulose acetophthalate
      gelispheres (CAPCA), for the purpose of obtaining linear, controlled drug
      release. This polymeric system, composed of sodium alginate, pectin, and
      cellulose acetophthalate, was developed through a binary crosslinking reaction in
      a composite aqueous system consisting of calcium and acetate ions. The
      crosslinking reaction was optimized in terms of maximizing drug release
      suppression and could be obtained by exposing the gelispheres for 24 hours to a
      combined aqueous solution of 15% w/v acetic acid and 2% w/v calcium chloride. The
      highly acidic nature of this solution (pH 1.9) was desirable for enhancing the
      drug entrapment efficiency of the gelispheres. Synchronization of matrix swelling
      and erosion appeared to be responsible for the attainment of zero-order drug
      release. However, such perfect synchronization was only achievable through
      application of the ternary polymeric combination presented in this work. The main
      advantages of the ternary system shown in this study over the previously
      presented binary calcium-alginate-pectinate system (CAP) proposed by Pillay and
      Fassihi (1999a, 1999b), was provision of extended drug release over 18 hours,
      minimization of late-phase drug release tapering, and provision of superior
      linearity in drug release profiles. Kinetic modeling of dissolution data using
      various power law equations highlighted the significance of matrix relaxation and
      erosion in modulation of drug release rate. In all cases of model fitting
      excellent correlation (r(2) > 0.98) was obtained between observed and predicted
      data. Textural profiling of crosslinked gelispheres reflected a significantly
      lower reduction in matrix resilience as the concentration of cellulose
      acetophthalate was increased in the gelisphere formulation. This may be
      attributed to the concentration-dependent matrix plastic-transforming property of
      cellulose acetophthalate.

PMID- 12055036
TI  - Delivery of LMW heparin via surface coated chitosan/peg-alginate microspheres
      prevents thrombosis.
AB  - Heparin remains the gold-standard inhibitor of the process involved in the
      vascular response to injury. Continued anticoagulation is achieved by
      subcutaneous administration of low-molecular-weight heparin (LMW Hep) or with an
      orally active anticoagulant such as warfarin. An oral heparin would avoid the
      inconvenience of subcutaneous injections and adverse events associated with
      warfarin. A mild chitosan/PEG/calcium alginate microencapsulation process, as
      applied to encapsulation of biological macromolecules such as heparin and LMW Hep
      was investigated. Heparin and LMW Hep entrapped alginate beads were further
      surface/enteric coated with chitosan and cellulose acetate phthalate (CAP) via
      carbodiimide (EDC) functionalities. It was observed that approximately 70% of the
      content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 hours
      and no significant release of LMW Hep was observed from enteric coated
      microspheres (12%) during treatment with 0.1 M HCl, pH 1.0 for 4 hours. But acid
      treated capsules had released almost all the entrapped LMW Hep into Tris-HCl, pH
      7.4 media within 6 hours. From scanning electron microscopic and swelling
      studies, it appeared that the surface coatings (via chitosan and CAP) had
      modified the alginate microspheres and subsequently the drug release. The
      released heparin and LMW Hep had shown their anticoagulant functions. These
      results established the feasibility of modifying the formulation in order to
      obtain the desired controlled release of bioactive agent (LMW Hep), for a
      convenient pH dependent delivery system.

PMID- 12055037
TI  - Beads of acryloylated polyaminoacidic matrices containing 5-Fluorouracil for drug
      delivery.
AB  - Spherical polymeric microparticles have been prepared by a reverse phase
      suspension polymerization technique. The starting polymer was alpha,beta-poly(N-2
      hydroxyethyl)-DL-aspartamide (PHEA), partially derivatized with
      glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) was crosslinked in the
      presence of N,N'-dimethylacrylamide (DMAA) or N,N'-ethylenebisacrylamide (EBA). 5
      fluorouracil was incorporated into PHG-DMAA or PHG-EBA beads both during and
      after the crosslinking process. Swelling studies revealed a high affinity toward
      aqueous medium, influenced by the presence of 5-fluorouracil. The in vitro
      release study showed that the release rate depends on the chemical structure of
      the beads and the procedure adopted to incorporate 5-fluorouracil into the
      microparticles.

PMID- 12055038
TI  - Antigenic and adjuvant activities of branched aliphatic oligoester (M-DL-LA)
      microspheres with incorporated bovine rotavirus.
AB  - Branched aliphatic oligoester microspheres (msp) with incorporated rotavirus were
      used to induce the production of systemic and mucosal antibodies in mice. The msp
      with a mean diameter of 7.4 microm were prepared by the w/o/w technique. The mice
      were immunized intraperitoneally or orally. High ELISA titres of systemic and
      local IgG and IgA antibodies were indicative of rotavirus incorporation and of
      the adjuvant activity of msp. Oral immunization with a split dose administered on
      three consecutive days, resulted in the production of systemic IgG and IgA
      antibodies, but failed to induce the production of mucosal antibodies even if the
      immunization dose was increased threefold. Specific antibodies were detectable in
      faeces of orally immunized mice only after another triple administration of the
      same dose in the fourth week of the experiment. Reactions of blood serum IgG with
      the structural viral proteins VP4, VP6, and VP7 were demonstrated by western
      blotting. Both systemic, and faecal IgA antibodies were specific for the VP6
      protein and the dimeric form of the glycoprotein VP4.

PMID- 12055039
TI  - Correlation between in vitro release and in vivo immune response from
      biodegradable polymer particles entrapping tetanus toxoid.
AB  - Release of immunoreactive antigen from biodegradable polymer particles in a
      manner mimicking the normal vaccination schedule is one of the most important
      requirements for the successful development of single dose vaccine formulation.
      Tetanus toxoid (TT) was used as a model antigen to develop single dose vaccine
      formulations using poly(lactide-co-glycolide) and poly(lactide)polymers. An
      amphiphilic stabilizer such as RSA or PVA was used at an optimal concentration in
      the internal aqueous phase during preparation of immunoreactive TT particles
      using the multiple emulsion solvent evaporation method. Particles made from
      different polymers released immunoreactive TT continuously for more than 4 months
      in vitro and release profiles were in accordance with the degradation
      characteristics of the polymer. Initial burst release of antigen from the
      particles was controlled by incorporation of different concentrations of PVA in
      the internal aqueous phase during particle formulation. The extent of antigen
      release from the particles was varied by changing the aqueous to organic phase
      volume during the primary emulsification stage of particles formulation. Use of
      above formulation variables resulted in the formulation of polymer particles
      having different in vitro release characteristics. Anti-TT antibody titers in
      vivo were also in accordance with the in vitro release characteristics of
      immunoreactive TT from the particles. Anti-TT antibody titers from the stabilized
      particles were much better than that observed from particles made without
      stabilizers. These results indicate the importance of stabilizers and different
      formulation variables for the preparation of polymer particles having desired in
      vitro release characteristics.

PMID- 12055040
TI  - Effects of vehicles and pressure sensitive adhesives on the penetration of
      isosorbide dinitrate across the hairless mouse skin.
AB  - The effects of various vehicles and adhesives on the percutaneous absorption of
      isosorbide dinitrate (ISDN) were evaluated. Lauroglycol FCC showed the highest
      flux among vehicles tested. The flux of ISDN from silicone and acrylic adhesive
      matrices was found to be higher than that from other types of adhesive matrices.
      No statistically significant relationship between the flux from acrylic PSA and
      the flux from a solution formulation was observed. A highly cross-linked acrylic
      adhesive gave higher permeation rates than the other acrylic adhesives examined.
      N-decylmethyl sulfoxide showed the highest enhancing effect on the flux of ISDN
      from acrylic adhesive. The relationship between the HLB values of vehicles and
      the measured flux showed a decrease of flux at HLB values greater than 12.

PMID- 12055041
TI  - Development and physical characterization of a periodontal bioadhesive gel of
      metronidazole.
AB  - To develop a localized drug delivery system that offers prolonged administration
      of metronidazole into the periodontal pocket, muccoadhesive gel formulations
      containing 5% w/w metronidazole were prepared using the bioadhesive polymers:
      carboxymethylcellulose, methylcellulose, hydroxyethylcellulose,
      polyvinylpirrolidone, and carbopol. Increased concentrations of the polymers
      decreased the drug release rate and enhanced syringeability, yield value, and
      adhesiveness but decreased the spreadability. The bioadhesive properties of the
      gels were affected by pH and Ca(2+) concentration. The gel containing 20%
      hydroxyethylcellulose, 20% polyvinylpirrolidone, and 1% carbopol exhibited zero
      order drug release kinetics and suitable physical properties for drug delivery to
      the periodontal pocket.

PMID- 12055043
TI  - Literature alerts.

PMID- 12055044
TI  - Teen smoking, field cancerization, and a "critical period" hypothesis for lung
      cancer susceptibility.
AB  - Cigarette smoking by children and adolescents continues to be prevalent, and this
      fact represents a major public health problem and challenge. Epidemiologic work
      has previously suggested that exposure of the lung to tobacco carcinogens at an
      early age may be an independent risk factor for lung cancer. Recent studies at
      the molecular and cellular levels are consistent with this, now suggesting that
      early exposure enhances DNA damage and is associated with the induction of DNA
      alterations in specific chromosomal regions. In this paper we hypothesize that
      adolescence, which is known to be the period of greatest development for the
      lung, may constitute a "critical period" in which tobacco carcinogens can induce
      fields of genetic alterations that make the early smoker more susceptible to the
      damaging effects of continued smoking. The fact that lung development differs by
      sex might also contribute to apparent gender differences in lung cancer
      susceptibility. Because this hypothesis has important implications for health
      policy and tobacco control, additional resources need to be devoted to its
      further evaluation. Targeted intervention in adolescent smoking may yield even
      greater reductions in lung cancer occurrence than otherwise anticipated.

PMID- 12055045
TI  - Lead poisoning among young children in Russia: concurrent evaluation of childhood
      lead exposure in Ekaterinburg, Krasnouralsk, and Volgograd.
AB  - The Gore-Chernomyrdin Commission encouraged a binational collaboration to
      evaluate pediatric lead poisoning in Russia. The study evaluated children in
      three Russian cities: Krasnouralsk, a small city with minimal traffic centered
      around a copper smelter; and Ekaterinburg and Volgograd, both of which are large
      cities with multiple factories and heavy vehicular traffic. This project was the
      first international use of portable blood lead analysis instruments. In each
      city, at least 90% of children attending selected neighborhood kindergartens
      participated. We selected kindergartens on the basis of their proximity to
      industrial areas and major traffic corridors. We obtained capillary blood samples
      and analyzed for lead content and hemoglobin (Hgb) levels in the field, and
      collected environmental samples (i.e., indoor dust, tap water, play area soil,
      and interior and exterior paint) and analyzed for each participating school and
      in the homes of about 10% of the children who had elevated blood lead levels
      (BLLs; greater than or equal to 10 microg/dL). We calculated all age-, sex-, and
      city-specific geometric means using generalized estimating equations to account
      for covariance within kindergartens, and used multivariate logistic regression
      models to identify variables predictive of elevated BLLs. Overall, 23% of study
      children had elevated BLLs and 2% were anemic, defined as Hgb < 11 g/dL.
      Krasnouralsk had the highest geometric mean BLL (10.7 microg/dL), the highest
      percentage of children (60%) with elevated BLLs, and the highest percentage of
      anemic children (4%). All soil samples in Krasnouralsk had detectable lead
      levels. Volgograd was the only city that had paint samples with elevated lead
      levels. We found apparent city-specific differences in the percentages of
      children with elevated BLLs. Lead-contaminated soil and dust, which can result
      from lead-based automotive fuel and from lead-related industrial emissions,
      appear to be the most important routes of lead exposure of those evaluated in
      this study. Elevated lead levels found in paint samples from Volgograd may
      indicate old undercoats of lead-based paint that could represent a regionally
      rather than nationally important source of exposure.

PMID- 12055046
TI  - Economic gains resulting from the reduction in children's exposure to lead in the
      United States.
AB  - In this study we quantify economic benefits from projected improvements in worker
      productivity resulting from the reduction in children's exposure to lead in the
      United States since 1976. We calculated the decline in blood lead levels (BLLs)
      from 1976 to 1999 on the basis of nationally representative National Health and
      Nutrition Examination Survey (NHANES) data collected during 1976 through 1980,
      1991 through 1994, and 1999. The decline in mean BLL in 1- to 5-year-old U.S.
      children from 1976-1980 to 1991-1994 was 12.3 microg/dL, and the estimated
      decline from 1976 to 1999 was 15.1 microg/dL. We assumed the change in cognitive
      ability resulting from declines in BLLs, on the basis of published meta-analyses,
      to be between 0.185 and 0.323 IQ points for each 1 g/dL blood lead concentration.
      These calculations imply that, because of falling BLLs, U.S. preschool-aged
      children in the late 1990s had IQs that were, on average, 2.2-4.7 points higher
      than they would have been if they had the blood lead distribution observed among
      U.S. preschool-aged children in the late 1970s. We estimated that each IQ point
      raises worker productivity 1.76-2.38%. With discounted lifetime earnings of
      $723,300 for each 2-year-old in 2000 dollars, the estimated economic benefit for
      each year's cohort of 3.8 million 2-year-old children ranges from $110 billion to
      $319 billion.

PMID- 12055047
TI  - The effect of house dust mite sensitization on lung size and airway caliber in
      symptomatic and nonsymptomatic preadolescent children: a community-based study in
      Poland.
AB  - There are conflicting reports on the effects of atopy on lung function. The
      purpose of this study was to compare the effects of house mite (HM) atopy on lung
      function in subsamples of 12-year-old symptomatic and nonsymptomatic
      preadolescent children taken from the community sample. An additional objective
      of this study was to identify possible environmental determinants of HM skin
      reaction. We obtained questionnaire data on respiratory symptoms and skin-prick
      tests and performed spirometry on a subsample of 311 children of a birth cohort
      of children who have been followed over 3 years. Multivariate regression analysis
      showed progressive decrement of lung function indices (forced vital capacity,
      forced expiratory volume in 1 sec, and forced expiratory flow, midexpiratory
      phase) with increasing degree of HM atopy reflected by the skin reaction to HM
      allergens. The apparent association between the level of HM atopy and the lung
      function indices was highly significant in symptomatic individuals but
      insignificant in nonsymptomatic subjects. HM sensitization was significantly
      associated with mother's atopy. It occurred predominantly in boys and was related
      to the use of coal or gas for house heating. The effect of allergen sensitization
      on lung size and airway caliber confined to symptomatic subjects may reflect the
      inflammatory status of bronchial airways in the symptomatic subjects.

PMID- 12055048
TI  - The influence of ambient coarse particulate matter on asthma hospitalization in
      children: case-crossover and time-series analyses.
AB  - In this study, we used both case-crossover and time-series analyses to assess the
      associations between size-fractionated particulate matter and asthma
      hospitalization among children 6-12 years old living in Toronto between 1981 and
      1993. Specifically, we used exposures averaged over periods varying from 1 to 7
      days to assess the effects of particulate matter on asthma hospitalization. We
      calculated estimates of the relative risk of asthma hospitalization adjusted for
      daily weather conditions (maximum and minimum temperatures, and average relative
      humidity) for an incremental exposure corresponding to the interquartile range in
      particulate matter. Both bidirectional case-crossover and time-series analyses
      revealed that coarse particulate matter (PM10-2.5) averaged over 5-6 days was
      significantly associated with asthma hospitalization in both males and females.
      The magnitude of this effect appeared to increase with increasing number of days
      of exposure averaging for most models, with the relative risk estimates
      stabilizing at about 6 days. Using a bidirectional case-crossover analysis, the
      estimated relative risks were 1.14 [95% confidence interval (CI), 1.02, 1.28] for
      males and 1.18 (95% CI, 1.02, 1.36) for females, for an increment of 8.4
      microg/m(3) in 6-day averages of PM10-2.5. The corresponding relative risk
      estimates were 1.10 and 1.18, respectively, when we used time-series analysis.
      The effect of PM10-2.5 remained positive after adjustment for the effects of the
      gaseous pollutants carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide
      (SO2), and ozone (O3). We did not find significant effects of fine particulate
      matter (PM2.5) or of thoracic particulate matter (PM10) on asthma
      hospitalizations using either of these two analytic approaches. For the most
      part, relative risk estimates from the unidirectional case-crossover analysis
      were more pronounced compared with both bidirectional case-crossover and time
      series analyses.

PMID- 12055049
TI  - Host and environmental determinants of polychlorinated aromatic hydrocarbons in
      serum of adolescents.
AB  - This study investigated host factors and environmental factors as potential
      determinants of polychlorinated aromatic hydrocarbons (PCAHs) in serum of
      adolescents. We recruited 200 participants (80 boys and 120 girls), with a mean
      age of 17.4 years (SD, 0.8), in Belgium from a rural control area (Peer) and from
      two polluted suburbs of Antwerp where a nonferrous smelter (Hoboken) and waste
      incinerators (Wilrijk) are located. We quantified polychlorinated biphenyls
      (PCBs; congeners 138, 153, and 180) in serum by gas chromatography and obtained
      the toxic equivalents (TEQs) of PCAHs in serum with the chemically activated
      luciferase gene expression bioassay (CALUX). Serum PCB concentration was higher
      in boys than in girls (1.67 vs. 1.02 nmol/L or 377 vs. 210 pmol/g serum lipids;
      p< 0.001). In the whole adolescent group, multiple regression showed that serum
      PCB concentration decreased 0.06 nmol/L per 1% increase in body fat content (p<
      0.001) and increased 0.39 nmol/L and 0.14 nmol/L per 1 mmol/L increase in serum
      concentrations of triglycerides (p < 0.001) and cholesterol (p = 0.002),
      respectively. Host factors explained 44% of the serum PCB variance. In the same
      model, serum PCB concentration increased 0.14 nmol/L with 10 weeks of breast
      feeding (p< 0.001) and 0.06 nmol/L with intake of 10 g animal fat per day (p <
      0.001), and was associated with residence in the waste incinerator area (9%
      higher; p = 0.04); 11% of the variance could be explained by these environmental
      factors. The geometric mean of the serum TEQ value was similar in boys and girls
      (0.15 TEQ ng/L or 33.0 pg/g serum lipids). In multiple regression, TEQ in serum
      decreased 0.03 ng/L per centimeter increase in triceps skinfold (p = 0.006) and
      was 29% higher in subjects living close to the nonferrous smelter (p < 0.001).
      This study showed that in 16- to 18-year-old teenagers host factors are important
      determinants of serum concentrations of PCAHs, whereas environmentally related
      determinants may to some extent contribute independently to human exposure to
      these persistent chemicals in the environment.

PMID- 12055050
TI  - GSTT1 and CYP2E1 polymorphisms and trihalomethanes in drinking water: effect on
      childhood leukemia.
AB  - The purpose of the study was to determine whether the risk of childhood acute
      lymphoblastic leukemia (ALL) associated with drinking water disinfection by
      products was modified in the presence of variants in genes involved in the
      metabolism of trihalomethanes (THMs). We included a subset of cases from a
      population-based case-control study in a case-only study to estimate the
      interaction odds ratios (IORs) between prenatal and postnatal exposure to THMs
      and polymorphisms in the GSTT1 and CYP2E1 genes. We compared cases with and
      without a given variant regarding their exposure to THMs using unconditional
      logistic regression. The IOR for a postnatal average of total THM above the 95th
      percentile with GSTT1 null genotype was 9.1 [95% confidence interval (95% CI),
      1.4-57.8]. With CYP2E1 (variant G-1259C, known as the allele CYP2E1*5), the
      effect of exposure during pregnancy for an average exposure to total THM at or
      above the 75th percentile was 9.7 (95% CI, 1.1-86.0). These results contrast
      strongly with those from our case-control analysis, in which we considered the
      exposure to THMs only in relation with ALL, and observed no increase in risk or
      very moderate ones. The present preliminary study shows suggestive but imprecise
      results. We found no similar results in the literature, underscoring the need for
      other studies as well as the potential usefulness of combining exposure and
      relevant genetic information in such studies.

PMID- 12055051
TI  - Immunologic biomarkers in relation to exposure markers of PCBs and dioxins in
      Flemish adolescents (Belgium).
AB  - In this study, we investigated 17- to 18-year-old boys and girls to determine
      whether changes in humoral or cellular immunity or respiratory complaints were
      related to blood serum levels of polychlorinated biphenyls (PCBs) and dioxin-like
      compounds after lifetime exposure in Flanders (Belgium). We obtained blood
      samples from and administered questionnaires to 200 adolescents recruited from a
      rural area and two urban suburbs. Physicians recorded medical history and
      respiratory diseases. We measured immunologic biomarkers such as differential
      blood cell counts, lymphocyte phenotypes, and serum immunoglobulins. As
      biomarkers of exposure, we determined the serum concentrations of PCBs (PCB 138,
      PCB 153, and PCB 180) and dioxin-like compounds [chemical-activated luciferase
      expression (CALUX) bioassay]. The percentages of eosinophils and natural killer
      cells in blood were negatively correlated with CALUX toxic equivalents (TEQs) in
      serum (p = 0.009 and p = 0.05, respectively). Increased serum CALUX TEQs resulted
      in an increase in serum IgA levels (p = 0.05). Furthermore, levels of specific
      IgEs (measured by radioallergosorbent tests) of cat dander, house dust mite, and
      grass pollen were also significantly and negatively associated with the CALUX
      TEQ, with odds ratios (ORs) equal to 0.63 [95% confidence interval (CI), 0.42
      0.96], 0.68 (0.5-0.93), and 0.70 (0.52-0.95), respectively. In addition, reported
      allergies of the upper airways and past use of antiallergic drugs were negatively
      associated with CALUX TEQs, with ORs equal to 0.66 (0.47-0.93) and 0.58 (0.39
      0.85), respectively. We found a negative association between IgGs and marker PCBs
      in serum (p = 0.009). This study shows that immunologic measurements and
      respiratory complaints in adolescents were associated with environmental exposure
      to polyhalogenated aromatic hydrocarbons (PHAHs). The negative correlation
      between PHAHs and allergic responses in adolescents suggested that exposure may
      entail alterations in the immune status.

PMID- 12055052
TI  - The exposure of nonsmoking and smoking mothers to environmental tobacco smoke
      during different gestational phases and fetal growth.
AB  - We studied the impact of maternal exposure to environmental tobacco smoke (ETS)
      on birth weight (BW), low birth weight (LBW), and intrauterine growth retardation
      (IUGR) according to self-reported maternal smoking habits in a sample of 6,866
      singleton births. We obtained data about parental characteristics and maternal
      active smoking (AS) and passive smoking at delivery via maternal questionnaires
      and medical records. We used three categories of smoking habits (nonsmokers and
      those who smoked 1-10 or >10 cigarettes per day) and defined ETS exposure as
      greater than or equal to 5 cigarettes per day smoked by others in the mother's
      presence. We used multiple regression and logistic regression procedures with
      adjustment for many associated covariates. We observed a significant reduction of
      the mean BW in infants of AS mothers. This reduction was only marginal for
      mothers who stopped smoking after recognizing their pregnancy. ETS exposure in
      1,797 of 5,507 nonsmoking mothers reduced the mean BW of their infants by 53 g
      [95% confidence interval (CI), 24-82 g]. ETS exposure also significantly reduced
      BW in babies of AS mothers by 92 g (CI, 21-113 g) compared with BW of ETS
      nonexposed AS mothers. The adjusted odds ratio (AOR) of LBW for ETS-exposed AS
      mothers was two times the LBW risk of ETS-nonexposed AS mothers(2.02; CI, 1.11
      3.67); the AOR of ETS-exposed nonsmoking mothers was 1.51 (CI, 1.02-2.26). The
      AOR of IUGR for this group did not differ from unity (1.08; CI, 0.82-1.43).
      However, ETS exposure increased the AOR of IUGR for AS mothers from 1.64 (CI,
      1.06-2.53) to 2.13 (CI, 1.70-2.67). ETS exposure reduced the BW of infants of
      nonsmoking mothers and contributed to additional BW reduction in infants of AS
      mothers. ETS exposure increased the risk of LBW but not that of IUGR in babies of
      nonsmoking mothers.

PMID- 12055054
TI  - A child with chronic manganese exposure from drinking water.
AB  - The patient's family bought a home in a suburb, but the proximity of the house to
      wetlands and its distance from the town water main prohibited connecting the
      house to town water. The family had a well drilled and they drank the well water
      for 5 years, despite the fact that the water was turbid, had a metallic taste,
      and left an orange-brown residue on clothes, dishes, and appliances. When the
      water was tested after 5 years of residential use, the manganese concentration
      was elevated (1.21 ppm; U.S. Environmental Protection Agency reference, < 0.05
      ppm). The family's 10-year-old son had elevated manganese concentrations in whole
      blood, urine, and hair. The blood manganese level of his brother was normal, but
      his hair manganese level was elevated. The patient, the 10-year-old, was in the
      fifth grade and had no history of learning problems; however, teachers had
      noticed his inattentiveness and lack of focus in the classroom. Our results of
      cognitive testing were normal, but tests of memory revealed a markedly below
      average performance: the patient's general memory index was at the 13th
      percentile, his verbal memory at the 19th percentile, his visual memory at the
      14th percentile, and his learning index at the 19th percentile. The patient's
      free recall and cued recall tests were all 0.5-1.5 standard deviations (1 SD =
      16th percentile) below normal. Psychometric testing scores showed normal IQ but
      unexpectedly poor verbal and visual memory. These findings are consistent with
      the known toxic effects of manganese, although a causal relationship cannot
      necessarily be inferred.

PMID- 12055055
TI  - Beyond The Bangkok Statement: research needs to address environmental threats to
      children's health.

PMID- 12055053
TI  - Environmental exposure to polychlorinated biphenyls and placental CYP1A1 activity
      in Inuit women from northern Quebec.
AB  - Some polychlorinated biphenyl (PCB) congeners are CYP1A1 inducers, and induction
      of this enzyme in the placenta has been linked to adverse effects on fetal
      development. The objective of this study was to determine if the body burden of
      PCBs is related to placental CYP1A1 activity in Inuit women from Nunavik
      (northern Quebec), a population highly exposed to organochlorines. Placenta and
      cord blood samples were obtained from 35 Inuit women and 30 women from a southern
      Quebec community exposed to background levels of organochlorines. We measured PCB
      concentrations in all cord plasma samples and in a subset of placenta samples
      from the Nunavik group and assessed CYP1A1 activity (ethoxyresorufin-O
      deethylase; EROD) in placental microsomes from all participants. Concentrations
      of PCBs in cord plasma were strongly correlated to those in placenta (Pearson's
      r) = 0.77-0.97, p < 0.001) and were on average 4-fold higher in Inuit women than
      in southern Quebec women [for PCB 153, the geometric means (geometric SDs) were
      83.3 (1.9) ng/g lipid vs. 16.9 (1.6) ng/g lipid, respectively]. Despite this
      difference in PCB body burden, both study groups had similar EROD activities when
      data were stratified according to tobacco smoking. Although simple correlation
      analysis first showed that placental EROD activity was correlated with PCB 153
      plasma concentration in the Nunavik group, a multivariate analysis failed to
      demonstrate a significant contribution of PCBs to EROD activity when tobacco
      smoking was included in the analysis. We conclude that dietary exposure to PCBs
      in Inuit women from Nunavik does not significantly influence EROD activity in the
      placenta, implicating tobacco smoking as the major modulating factor.

PMID- 12055056
TI  - Carrageenan: a safe additive.

PMID- 12055057
TI  - World's children threatened.

PMID- 12055059
TI  - Learning the hard way: the poor environment of America's schools.

PMID- 12055058
TI  - Soy and children's health: a formula for trouble.

PMID- 12055060
TI  - Reading, writing, but no arithmetic: healthier schools legislated but funding
      lags.

PMID- 12055061
TI  - Chemical contaminants in breast milk and their impacts on children's health: an
      overview.
AB  - Human milk is the best source of nutrition for infants. Breast milk contains the
      optimal balance of fats, carbohydrates, and proteins for developing babies, and
      it provides a range of benefits for growth, immunity, and development.
      Unfortunately, breast milk is not pristine. Contamination of human milk is
      widespread and is the consequence of decades of inadequately controlled pollution
      of the environment by toxic chemicals. The finding of toxic chemicals in breast
      milk raises important issues for pediatric practice, for the practice of public
      health, and for the environmental health research community. It also illuminates
      gaps in current knowledge including a) insufficient information on the nature and
      levels of contaminants in breast milk; b) lack of consistent protocols for
      collecting and analyzing breast milk samples; c) lack of toxicokinetic data; and
      d) lack of data on health outcomes that may be produced in infants by exposure to
      chemicals in breast milk. These gaps in information impede risk assessment and
      make difficult the formulation of evidence-based health guidance. To address
      these issues, there is a need for a carefully planned and conducted national
      breast milk monitoring effort in the United States. Additionally, to assess
      health outcomes of toxic exposures via breast milk, it will be necessary to
      examine children prospectively over many years in longitudinal epidemiologic
      studies that use standardized examination protocols that specifically assess
      breast milk exposures. Finally, current risk assessment methods need to be
      expanded to include consideration of the potential risks posed to infants and
      children by exposures to chemical residues in breast milk.

PMID- 12055062
TI  - Analytic considerations for measuring environmental chemicals in breast milk.
AB  - The presence of environmental chemicals in human breast milk is of general
      concern because of the potential health consequence of these chemicals to the
      breast-fed infant and the mother. In addition to the mother's exposure, several
      features determine the presence of environmental chemicals in breast milk and
      their ability to be determined analytically. These include maternal factors and
      properties of the environmental chemical--both physical and chemical--such as its
      lipid solubility, degree of ionization, and molecular weight. Environmental
      chemicals with high lipid solubility are likely to be found in breast milk; they
      include polyhalogenated compounds such as polychlorinated biphenyls,
      polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, organochlorine
      insecticides, and polybrominated diphenylethers. These fat-soluble chemicals are
      incorporated into the milk as it is synthesized, and they must be measured in
      accordance with the fat content of the milk to allow for meaningful comparisons
      within an individual and among populations. Although the analytic approach
      selected to measure the environmental chemical is predominantly determined by the
      characteristics of the chemical, the concentration of the chemical in the milk
      sample and the existence of structurally similar chemicals (e.g., congeners) must
      be considered as well. In general, the analytic approach for measuring
      environmental chemicals in breast milk is similar to the approach for measuring
      the same chemicals in other matrices, except special considerations must be given
      for the relatively high fat content of milk. The continued efforts of
      environmental scientists to measure environmental chemicals in breast milk is
      important for defining the true contribution of these chemicals to public health,
      especially to the health of the newborn. Work is needed for identifying and
      quantifying additional environmental chemicals in breast milk from the general
      population and for developing analytic methods that have increased sensitivity
      and the ability to speciate various chemicals.

PMID- 12055063
TI  - Infant exposure to dioxin-like compounds in breast milk.
AB  - We used a one-compartment, first-order pharmacokinetic model to predict the
      infant body burden of dioxin-like compounds that results from breast-feeding.
      Validation testing of the model showed a good match between predictions and
      measurements of dioxin toxic equivalents (TEQs) in breast-fed infants, and the
      exercise highlighted the importance of the assumption of the rate of dissipation
      of TEQs in the infant. We evaluated five nursing scenarios: no nursing (i.e.,
      formula only), and nursing for 6 weeks, 6 months, 1 year, and 2 years. We assumed
      that an infant weighs 3.3 kg at birth and is exposed to a total of 800 pg TEQ/day
      by consumption of breast milk, leading to an estimated body weight-based dose of
      242 pg TEQ/kg-day, which drops to 18 pg TEQ/kg-day after 1 year. This decline is
      due to declines in dioxin concentration in mother's milk and infant body weight
      increases. This range is significantly higher, on a body-weight basis, than adult
      TEQ exposure, which has been estimated to average about 1 pg TEQ/kg-day. For the
      nursing scenarios of >or= 6 months, we predict that body burdens (expressed as a
      body lipid concentration) peak at around 9 weeks at 44 ppt TEQ lipid. We predict
      that the body burden of the formula-fed infants will remain below 10 ppt TEQ
      lipid during the first year. These results compare to the current adult average
      body burden of 25 ppt TEQ lipid. We also found that an infant who had been breast
      fed for 1 year had an accumulated dose 6 times higher than a 1-year-old infant
      who had not been breast-fed. For a 70-year lifetime, individuals who had been
      breast-fed had an accumulated dose 3-18% higher than individuals who had not been
      breast-fed.

PMID- 12055064
TI  - Pharmacokinetics of toxic chemicals in breast milk: use of PBPK models to predict
      infant exposure.
AB  - Factors controlling the transfer of potentially toxic chemicals in the breast
      milk of nursing mothers include both chemical characteristics, such as
      lipophilicity, and physiologic changes during lactation. Physiologically based
      pharmacokinetic (PBPK) models can aid in the prediction of infant exposure via
      breast milk. Benefits of these quantitative models include the ability to account
      for changing maternal physiology and transfer kinetics, as well as the chemical
      specific characteristics, in order to produce more accurate estimates of neonatal
      risk. A recently developed PBPK model for perchlorate and iodide kinetics in the
      lactating and neonatal rat demonstrates the utility of PBPK modeling in
      predicting maternal and neonatal distribution of these two compounds. This model
      incorporates time-dependent changes in physiologic characteristics and includes
      interactions between iodide and perchlorate that alter the distribution and
      kinetics of iodide.

PMID- 12055066
TI  - Global perspectives in breast milk contamination: infectious and toxic hazards.
AB  - Breast milk is the natural and optimal food for infants. In addition to meeting
      nutritional needs, breast milk provides numerous immunologic, developmental,
      psychologic, economic, and practical advantages. It is postulated that breast
      feeding may also be related to the prevention of some adult health problems such
      as diabetes and coronary heart disease. Malnutrition among infants and young
      children, which remains one of the most severe global public health problems, is
      among the main reasons that the World Health Organization (WHO) so strongly
      supports breast-feeding. However, WHO recognizes the growing concern expressed by
      scientists, health professionals, environmentalists, and mothers about the
      potential risks posed by the presence of toxicants and infectious agents in
      breast milk. In this paper we review the main infectious hazards (tuberculosis,
      hepatitis B, and human immunodeficiency virus) and selected chemical hazards
      (tobacco, persistent contaminants) and the activities undertaken by WHO. We
      conclude that in cases where there is a high degree of pollution from chemical
      sources occurring simultaneously in a bacterially contaminated environment, the
      choice is not simply between polluted breast milk and risk-free substitutes.
      Rather, informed choice is based on assessing the known and unknown risks of
      artificial feeding versus the unknown, but potential, risks of chemical
      contamination of breast milk. Clearly, the possible toxicity of compounds
      requires further investigation. Of much greater importance, however, are
      effective measures to protect the environment for the entire population by
      controlling the use of these toxic products. Current scientific evidence does not
      support altering WHO's global public health recommendation of exclusive breast
      feeding for 6 months followed by safe and appropriate complementary foods, with
      continued breast-feeding, up to 2 years of age or beyond.

PMID- 12055068
TI  - Cross signaling, cell specificity, and physiology.
AB  - The literature on intracellular signal transduction presents a confusing picture:
      every regulatory factor appears to be regulated by all signal transduction
      cascades and to regulate all cell processes. This contrasts with the known
      exquisite specificity of action of extracellular signals in different cell types
      in vivo. The confusion of the in vitro literature is shown to arise from several
      causes: the inevitable artifacts inherent in reductionism, the arguments used to
      establish causal effect relationships, the use of less than adequate models (cell
      lines, transfections, acellular systems, etc.), and the implicit assumption that
      networks of regulations are universal whereas they are in fact cell and stage
      specific. Cell specificity results from the existence in any cell type of a
      unique set of proteins and their isoforms at each level of signal transduction
      cascades, from the space structure of their components, from their combinatorial
      logic at each level, from the presence of modulators of signal transduction
      proteins and of modulators of modulators, from the time structure of
      extracellular signals and of their transduction, and from quantitative
      differences of expression of similar sets of factors.

PMID- 12055065
TI  - Chemical contaminants in breast milk: time trends and regional variability.
AB  - Research on environmentally related chemical contaminants in breast milk spans
      several decades and dozens of countries. The ability to use this research as an
      environmental indicator is limited because of a lack of consistent protocols.
      Data on xenobiotics in breast milk are influenced by choices in sample selection,
      sample pooling, analysis, and reporting. In addition, most studies have focused
      only on a small panel of persistent organic pollutants, despite indications that
      a wide range of additional chemical contaminants may also enter breast milk.
      Despite these limitations, however, it is possible to draw some generalizations.
      In this paper we review available data on levels of organochlorine pesticides,
      polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs),
      polybrominated diphenyl ethers (PBDEs), metals, and solvents in breast milk.
      Examples drawn from around the world illustrate the available data and the
      patterns that have appeared in various areas over time. Over the past few
      decades, levels of the organochlorine pesticides, PCBs, and dioxins have declined
      in breast milk in countries where these chemicals have been banned or otherwise
      regulated. In contrast, the levels of PBDEs are rising. Regional differences in
      levels of xenobiotics in breast milk are related to historical and current local
      use patterns. Diet is a major factor that influences breast milk levels of
      persistent organic pollutants, with patterns in fish consumption playing a
      particularly significant role. Improved global breast milk monitoring programs
      would allow for more consistent data on trends over time, detection of new
      xenobiotics in breast milk, and identification of disproportionately exposed
      populations.

PMID- 12055069
TI  - Focus on "Claudins create charge-selective channels in the paracellular pathway
      between epithelial cells".

PMID- 12055070
TI  - MAP kinases contribute to IL-8 secretion by intestinal epithelial cells via a
      posttranscriptional mechanism.
AB  - The intracellular pathways that regulate intestinal epithelial gene expression
      are poorly understood. In this study we examined the roles of extracellular
      signal-regulated kinase (ERK) and p38 in the expression of interleukin-8 (IL-8)
      and intercellular adhesion molecule-1 (ICAM-1) using the human intestinal cell
      line HT-29. HT-29 cells were treated with tumor necrosis factor-alpha (TNF-alpha)
      in the presence or absence of ERK and p38 pathway inhibitors. TNF-alpha treatment
      resulted in increased IL-8 and ICAM-1 protein and mRNA synthesis, increased ERK
      and p38 activity, and activation of the transcription factors activator protein-1
      (AP-1) and nuclear factor-kappaB (NF-kappaB). Inhibition of the ERK and p38
      pathways attenuated IL-8 secretion but did not alter ICAM-1 expression.
      Furthermore, AP-1 and NF-kappaB DNA binding was not affected by ERK and p38
      inhibition. In contrast, ERK and p38 inhibition resulted in the accelerated
      degradation of the IL-8 mRNA, suggesting that in HT-29 cells, p38 and ERK
      contribute to TNF-alpha-stimulated IL-8 secretion by intestinal epithelial cells
      via a posttranscriptional mechanism that involves stabilization of the IL-8
      transcript.

PMID- 12055071
TI  - Prolonged force increase following a high-frequency burst is not due to a
      sustained elevation of [Ca2+]i.
AB  - A brief high-frequency burst of action potentials results in a sustained force
      increase in skeletal muscle. The present study investigates whether this force
      potentiation is the result of a sustained increase of the free myoplasmic [Ca2+]
      ([Ca2+]i). Single fibers from mouse flexor brevis muscles were stimulated with
      three impulses at 150 Hz (triplet) at the start of a 350-ms tetanus or in the
      middle of a 700-ms tetanus; the stimulation frequency of the rest of the tetanus
      ranged from 20 to 60 Hz. After the triplet, force was significantly (P < 0.05)
      increased between 17 and 20% when the triplet was given at the start of the
      tetanus and between 5 and 18% when the triplet was given in the middle (n = 7).
      However, during this potentiation, [Ca2+]i was not consistently increased. Hence,
      the increased force following a high-frequency burst is likely due to changes in
      the myofibrillar properties.

PMID- 12055072
TI  - A role for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic
      signaling in the human neutrophil.
AB  - The proinflammatory cytokine tumor necrosis factor (TNF)-alpha has been
      implicated in the attenuation of neutrophil spontaneous apoptosis during sepsis.
      Antiapoptotic signaling is principally mediated through the p60TNF receptor
      (p60TNFR). In neutrophils, TNF-alpha is an incomplete secretagogue and requires
      input from a ligated integrin(s) for neutrophil activation. In adherent
      neutrophils, TNF-alpha triggers association of both protein kinase C (PKC)-delta
      and phosphatidylinositol (PI) 3-kinase with the p60TNFR. In this study, a role
      for PKC-delta and PI 3-kinase in TNF-alpha-mediated antiapoptotic signaling was
      examined. TNF-alpha inhibited spontaneous apoptosis in fibronectin-adherent
      neutrophils, and this antiapoptotic signaling was blocked by the PKC-delta
      inhibitor rottlerin, but not by an inhibitor of Ca(2+)-dependent PKC isotypes, Go
      6976. Inhibition of PI 3-kinase by LY-294002 also inhibited TNF-alpha-mediated
      antiapoptotic signaling. Cycloheximide blocked TNF-alpha-mediated antiapoptotic
      signaling, suggesting protein synthesis is required. Inhibition of either PKC
      delta or PI 3-kinase attenuated TNF-alpha-mediated activation of the
      antiapoptotic transcription factor NFkappaB. Thus both PKC-delta and PI 3-kinase
      have essential roles in TNF-alpha-mediated antiapoptotic signaling in adherent
      neutrophils.

PMID- 12055073
TI  - NF-kappaB induced by IL-1beta inhibits elastin transcription and myofibroblast
      phenotype.
AB  - Interleukin (IL)-1beta released after lung injury regulates the production of
      extracellular matrix components. We found that IL-1beta treatment reduced the
      rate of elastin gene transcription by 74% in neonatal rat lung fibroblasts.
      Deletion analysis of the rat elastin promoter detected a cis-acting element
      located at -118 to -102 bp that strongly bound Sp1 and Sp3 but not nuclear factor
      (NF)-kappaB. This element mediated IL-1beta-induced inhibition of the elastin
      promoter. IL-1beta treatment did not affect the level of Sp1 but did induce
      translocation of the p65 subunit of NF-kappaB. Overexpression of p65 decreased
      elastin promoter activity and markedly reduced elastin mRNA. Immunoprecipitation
      studies indicated an interaction between the p65 subunit and Sp1 protein.
      Microarray analysis of mRNA isolated after overexpression of p65 or treatment
      with IL-1beta revealed downregulation of alpha-smooth muscle actin and calponin
      mRNAs. Expression of these genes is associated with the myofibroblast phenotype.
      These results indicate that IL-1beta activates the nuclear localization of NF
      kappaB that subsequently interacts with Sp1 to downregulate elastin transcription
      and expression of the myofibroblast phenotype.

PMID- 12055074
TI  - Potential role for Id myogenic repressors in apoptosis and attenuation of
      hypertrophy in muscles of aged rats.
AB  - Aging attenuates the overload-induced increase in myogenic regulatory
      transcription factor (MRF) expression and the extent of muscle enlargement. To
      identify whether mRNA levels of repressors of the MRFs are greater in overloaded
      muscles from aged animals, overload was achieved in plantaris muscle of aged (33
      mo; n = 14) and adult (9 mo; n = 17) rats. After 14 days, plantaris muscles in
      the overloaded limb were ~25% and 6% larger in adult and aged rats, respectively,
      compared with the contralateral limb. Hypertrophied muscles of adult rats had
      significantly greater levels of mRNA and protein levels for myogenin and MyoD
      compared with control muscles, but neither MRF increased with overload in muscles
      of aged rats. Muscles of aged rats had greater Id mRNA (150-700%) and protein
      repressor (200-6,000%) levels compared with adult rats. BAX and caspase 9 protein
      levels were 9,500% and 300% greater, respectively, in both control and
      hypertrophied muscles of aged rats compared with young adult rats. These data are
      consistent with the hypothesis that aging increases Id transcripts that activate
      apoptotic pathways involving BAX. This may contribute to sarcopenia by
      attenuating MRF protein levels in muscles of old animals.

PMID- 12055075
TI  - Pore formation is not associated with macroscopic redistribution of P2X7
      receptors.
AB  - The present study examines whether changes in P2X7 purinergic receptor density
      precede formation of the cytolytic pore characteristic of this receptor. We fused
      P2X7 receptors with enhanced green fluorescent protein (EGFP) at the amino or
      carboxy termini (EGFP-P2X7 and P2X7-EGFP). Electrophysiological characterization
      in Xenopus oocytes revealed wild-type responses to ATP for GFP-tagged receptors.
      However, differences in sensitivity to ATP were apparent with the P2X7-EGFP
      receptor displaying a threefold reduction in ATP sensitivity compared with
      control. Ethidium ion uptake was used to measure cytolytic pore formation.
      Comparison of tagged receptors with wild type in HEK-293 and COS-7 cells showed
      there was no significant difference in ethidium ion uptake, suggesting that
      fusions with EGFP did not interfere with cytolytic pore formation. Confocal
      microscopy confirmed that tagged receptors localized to the plasmalemma.
      Simultaneous monitoring of EGFP and ethidium ion fluorescence revealed that
      changes in receptor distribution do not precede pore formation. We conclude that
      it is unlikely that large scale changes in P2X7 receptor density precede pore
      formation.

PMID- 12055076
TI  - Inhibition of sarcoplasmic reticulum Ca2+-ATPase by miconazole.
AB  - The inhibition of sarcoplasmic reticulum Ca2+-ATPase activity by miconazole was
      dependent on the concentration of ATP and membrane protein. Half-maximal
      inhibition was observed at 12 microM miconazole when the ATP concentration was 50
      microM and the membrane protein was 0.05 mg/ml. When ATP was 1 mM, a low
      micromolar concentration of miconazole activated the enzyme, whereas higher
      concentrations inhibited it. A qualitatively similar response was observed when
      Ca2+ transport was measured. Likewise, the half-maximal inhibition value was
      higher when the membrane concentration was raised. Phosphorylation studies
      carried out after sample preequilibration in different experimental settings shed
      light on key partial reactions such as Ca2+ binding and ATP phosphorylation. The
      miconazole effect on Ca2+-ATPase activity can be attributed to stabilization of
      the Ca2+-free enzyme conformation giving rise to a decrease in the rate of the
      Ca2+ binding transition. The phosphoryl transfer reaction was not affected by
      miconazole.

PMID- 12055077
TI  - Adhesion of flowing monocytes to hypoxia-reoxygenation-exposed endothelial cells:
      role of Rac1, ROS, and VCAM-1.
AB  - Production of reactive oxygen species (ROS) by ischemic tissue after ischemia
      reperfusion (I/RP) is an important factor that contributes to tissue injury. The
      small GTPase Rac1 mediates the oxidative burst, and ROS act on signaling pathways
      involved in expression of inflammatory genes. Because there is evidence
      implicating monocytes in the pathogenesis of I/RP injury, our objective was to
      determine the molecular mechanisms that regulate adhesive interactions between
      monocytes and hypoxia-reoxygenation (H/RO)-exposed cultured endothelial cells
      (ECs). When U937 cells were perfused over human umbilical vein ECs at 1 dyn/cm2,
      H (1 h at 1% O2)/RO (13 h) significantly increased the fluxes of rolling and
      stably adherent U937 cells. Either EC treatment with the antioxidant pyrrolidine
      dithiocarbamate (PDTC) or infection with AdRac1N17, which results in expression
      of the dominant-negative form of Rac1, abolished H/RO-induced ROS production,
      attenuated rolling, and abolished stable adhesion of U937 cells to H/RO-exposed
      ECs. Infection with AdRac1N17 also abolished H/RO-induced upregulation of
      vascular cell adhesion molecule (VCAM)-1. In turn, blocking VCAM-1 abolished U937
      cell stable adhesion and slightly increased rolling. We concluded that the Rac1
      dependent ROS partially regulate rolling and exclusively regulate stable adhesion
      of monocytic cells to ECs after H/RO and that stable adhesion, but not rolling,
      is mediated by ROS-induced expression of VCAM-1.

PMID- 12055078
TI  - Alternative splicing yields novel BMAL2 variants: tissue distribution and
      functional characterization.
AB  - The BMAL2 gene encodes a member of the basic helix-loop-helix PER-ARNT-SIM family
      of transcription factors, which control diverse physiological processes including
      circadian rhythms. We identified four novel human BMAL2 transcripts that differ
      by alternative splicing within their NH2-terminal regions. Divergent expression
      of these and previously reported transcripts was observed among human tissues.
      The functional consequences of alternative splicing for transcriptional
      activation by CLOCK:BMAL2 heterodimers were assessed using luciferase reporter
      gene constructs that contained one of three diurnally regulated promoters,
      namely, those of the mouse period1, mouse vasopressin, and human plasminogen
      activator inhibitor-1 genes. These studies revealed that alternative splicing
      generates BMAL2 isoforms possessing high, medium, low, or no transcriptional
      activity. Similar results were obtained with each promoter, suggesting that
      alternative splicing may influence the amplitudes of both central and peripheral
      oscillators. Indeed, alternative splicing of BMAL2 may provide tissues with a
      rheostat capable of regulating CLOCK:BMAL2 heterodimer function across a broad
      continuum of potential transcriptional activities to accommodate varied metabolic
      demands and physiological roles.

PMID- 12055079
TI  - RhoA exerts a permissive effect on volume-regulated anion channels in vascular
      endothelial cells.
AB  - Cell swelling triggers in most cell types an outwardly rectifying anion current,
      I(Cl,swell), via volume-regulated anion channels (VRACs). We have previously
      demonstrated in calf pulmonary artery endothelial (CPAE) cells that inhibition of
      the Rho/Rho kinase/myosin light chain phosphorylation pathway reduces the
      swelling-dependent activation of I(Cl,swell). However, these experiments did not
      allow us to discriminate between a direct activator role or a permissive effect.
      We now show that the Rho pathway did not affect VRAC activity if this pathway was
      activated by transfecting CPAE cells with constitutively active isoforms of
      Galpha (a Rho activating heterotrimeric G protein subunit), Rho, or Rho kinase.
      Furthermore, biochemical and morphological analysis failed to demonstrate
      activation of the Rho pathway during hypotonic cell swelling. Finally,
      manipulating the Rho pathway with either guanosine 5'-O-(3-thiotriphosphate) or
      C3 exoenzyme had no effect on VRACs in caveolin-1-expressing Caco-2 cells. We
      conclude that the Rho pathway exerts a permissive effect on VRACs in CPAE cells,
      i.e., swelling-induced opening of VRACs requires a functional Rho pathway, but
      not an activation of the Rho pathway.

PMID- 12055080
TI  - Rabbit retinal neurons and glia express a variety of ENaC/DEG subunits.
AB  - Some members of the epithelial Na+ channel/degenerin (ENaC/DEG) family of ion
      channels have been detected in mammalian brain. Therefore, we examined the RNA
      and protein expression of these channels in another part of the central nervous
      system, the rabbit retina. We next sought to demonstrate physiological evidence
      for an amiloride-sensitive current in Muller glia, which, on the basis of a
      previous study, are thought to express alpha-ENaC (Golestaneh N, de Kozak Y,
      Klein C, and Mirshahi M. Glia 33: 160-168, 2001). RT-PCR of retinal RNA revealed
      the presence of alpha-, beta-, gamma-, and delta-ENaC as well as acid-sensing ion
      channel (ASIC)1, ASIC2, ASIC3, and ASIC4. Immunohistochemical localization with
      antibodies against alpha-ENaC and beta-ENaC showed labeling in Muller cells and
      neurons, respectively. The presence of alpha-ENaC, beta-ENaC, and ASIC1 was
      detected by Western blotting. Cultured Muller cells were whole cell patch
      clamped. These cells exhibited an inward Na+ current that was blocked by
      amiloride. These data demonstrate for the first time both the expression of a
      variety of ENaC and ASIC subunits in the rabbit retina as well as distinct
      cellular expression patterns of specific subunits in neurons and glia.

PMID- 12055081
TI  - Single cysteine to tyrosine transition inactivates the growth inhibitory function
      of Piedmontese myostatin.
AB  - Myostatin, a member of the transforming growth factor-beta superfamily, is a
      secreted growth factor that is proteolytically processed to give COOH-terminal
      mature myostatin and NH2-terminal latency-associated peptide in myoblasts.
      Piedmontese cattle are a heavy-muscled breed that express a mutated form of
      myostatin in which cysteine (313) is substituted with tyrosine. Here we have
      characterized the biology of this mutated Piedmontese myostatin. Northern and
      Western analyses indicate that there is increased expression of myostatin mRNA
      and precursor myostatin protein in the skeletal muscle of Piedmontese cattle. In
      contrast, a decrease in mature myostatin was observed in Piedmontese skeletal
      muscle. However, there is no detectable change in the circulatory levels of
      mature myostatin in Piedmontese cattle. Myoblast proliferation assay performed
      with normal and Piedmontese myostatin indicated that mature wild-type myostatin
      protein inhibited the proliferation of C2C12 myoblasts. Piedmontese myostatin, by
      contrast, failed to inhibit myoblast proliferation. In addition, when added in
      molar excess, Piedmontese myostatin acted as a potent "competitive inhibitor"
      molecule. These results indicate that, in Piedmontese myostatin, substitution of
      cysteine with tyrosine results in the distortion of the "cystine knot" structure
      and a loss of biological activity of the myostatin. This mutation also appears to
      affect either processing or stability of mature myostatin without altering the
      secretion of myostatin.

PMID- 12055082
TI  - Claudins create charge-selective channels in the paracellular pathway between
      epithelial cells.
AB  - Epithelia separate tissue spaces by regulating the passage of ions, solutes, and
      water through both the transcellular and paracellular pathways. Paracellular
      permeability is defined by intercellular tight junctions, which vary widely among
      tissues with respect to solute flux, electrical resistance, and ionic charge
      selectivity. To test the hypothesis that members of the claudin family of tight
      junction proteins create charge selectivity, we assessed the effect of reversing
      the charge of selected extracellular amino acids in two claudins using site
      directed mutagenesis. Claudins were expressed in cultured Madin-Darby canine
      kidney cell monolayers under an inducible promoter, and clones were compared with
      and without induction for transmonolayer electrical resistance and dilution
      potentials. Expression and localization of claudins were determined by
      immunoblotting, immunofluorescence microscopy, and freeze-fracture electron
      microscopy. We observed that substituting a negative for a positive charge at
      position 65 in the first extracellular domain of claudin-4 increased paracellular
      Na+ permeability. Conversely, substituting positive for negative charges at three
      positions in the first extracellular domain of claudin-15, singly and in
      combination, reversed paracellular charge selectivity from a preference for Na+
      to Cl-. These results support a model where claudins create charge-selective
      channels in the paracellular space.

PMID- 12055083
TI  - Oxidative stress inactivates the human DNA mismatch repair system.
AB  - In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSalpha and
      hMutSbeta complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2
      form the hMutLalpha heterodimer. These complexes, together with other components
      in the MMR system, correct single-base mismatches and small insertion/deletion
      loops that occur during DNA replication. Microsatellite instability (MSI) occurs
      when the loops in DNA microsatellites are not corrected because of a
      malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically
      inflamed tissues in the absence of genetic inactivation of the MMR system. We
      hypothesize that oxidative stress associated with chronic inflammation might
      damage protein components of the MMR system, leading to its functional
      inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2
      inactivate both single-base mismatch and loop repair activities of the MMR system
      in a dose-dependent fashion. On the basis of in vitro complementation assays
      using recombinant MMR proteins, we show that this inactivation is most likely due
      to oxidative damage to hMutSalpha, hMutSbeta, and hMutLalpha protein complexes.
      We speculate that inactivation of the MMR function in response to oxidative
      stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues
      associated with chronic inflammation.

PMID- 12055084
TI  - An ancient prevertebrate Na+-nucleoside cotransporter (hfCNT) from the Pacific
      hagfish (Eptatretus stouti).
AB  - The human concentrative (Na+-linked) plasma membrane transport proteins hCNT1,
      hCNT2, and hCNT3 are pyrimidine nucleoside-selective (system cit), purine
      nucleoside-selective (system cif), or broadly selective for both pyrimidine and
      purine nucleosides (system cib), respectively. All have orthologs in other
      mammalian species and belong to a gene family (CNT) that has members in insects,
      nematodes, pathogenic yeast, and bacteria. Here, we report the cDNA cloning and
      functional characterization of a CNT family member from an ancient marine
      prevertebrate, the Pacific hagfish (Eptatretus stouti). This Na+-nucleoside
      symporter, designated hfCNT, is the first transport protein to be characterized
      in detail in hagfish and is a 683-amino acid residue protein with 13 predicted
      transmembrane helical segments (TMs). hfCNT was 52, 50, and 57% identical in
      sequence to hCNT1, hCNT2, and hCNT3, respectively. Similarity to hCNT3 was
      particularly marked in the TM 4-13 region. When produced in Xenopus oocytes,
      hfCNT exhibited the transport properties of system cib, with uridine, thymidine,
      and inosine apparent K(m) values of 10-45 microM. The antiviral nucleoside drugs
      3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, and 2',3'-dideoxyinosine were
      also transported. Simultaneous measurement of uridine-evoked currents and
      radiolabeled uridine uptake under voltage-clamp conditions gave a Na+-to-uridine
      coupling ratio of 2:1 (cf. 2:1 for hCNT3 and 1:1 for hCNT1/2). The apparent K50
      value for Na+ activation was >100 mM. A 50:50 chimera between hfCNT and hCNT1
      (TMs 7-13 of hfCNT replaced by those of hCNT1) exhibited hCNT1-like cation
      interactions, establishing that the structural determinants of cation
      stoichiometry and binding affinity were located within the carboxy-terminal half
      of the protein. The high degree of sequence similarity between hfCNT and hCNT3
      may indicate functional constraints on the primary structure of the transporter
      and suggests that cib-type CNTs fulfill important physiological functions.

PMID- 12055085
TI  - K+-induced twitch potentiation is not due to longer action potential.
AB  - The objective of this study was to determine whether an increased duration of the
      action potential contributes to the K+-induced twitch potentiation at 37 degrees
      C. Twitch contractions were elicited by field stimulation, and action potentials
      were measured with conventional microelectrodes. For mouse extensor digitorum
      longus (EDL) muscle, twitch force was greater at 7-13 mM K+ than at 4.7 mM
      (control). For soleus muscle, twitch force potentiation was observed between 7
      and 11 mM K+. Time to peak and half-relaxation time were not affected by the
      increase in extracellular K+ concentration in EDL muscle, whereas both parameters
      became significantly longer in soleus muscle. Decrease in overshoot and
      prolongation of the action potential duration observed at 9 and 11 mM K+ were
      mimicked when muscles were respectively exposed to 25 and 50 nM tetrodotoxin
      (TTX; used to partially block Na+ channels). Despite similar action potentials,
      twitch force was not potentiated by TTX. It is therefore suggested that the K+
      induced potentiation of the twitch in EDL muscle is not due to a prolongation of
      the action potential and contraction time, whereas a longer contraction,
      especially the relaxation phase, may contribute to the potentiation in soleus
      muscle.

PMID- 12055086
TI  - Role of nitric oxide in the regulation of HIF-1alpha expression during hypoxia.
AB  - Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor
      consisting of HIF-1alpha and HIF-1beta subunits, controls the expression of a
      large number of genes involved in the regulation of cellular responses to reduced
      oxygen availability. The oxygen-regulated subunit, HIF-1alpha, is stabilized in
      cells exposed to hypoxia. The regulation of hypoxic responses by nitric oxide
      (NO) is believed to have wide pathophysiological relevance, thus we investigated
      whether NO affects HIF-1 activation in hypoxic cells. Here we show that NO
      generated from NO donors prevented HIF-1alpha hypoxic accumulation in Hep 3B and
      PC-12 cells. Addition of a glutathione analog or peroxynitrite scavengers
      prevented the NO-induced inhibition of HIF-1alpha accumulation in both cell
      lines. Exposure to NO was associated with inhibition of mitochondrial electron
      transport and compensatory glycolysis, which maintained normal cellular ATP
      content. Succinate, a Krebs cycle intermediate and respiratory chain substrate,
      restored HIF-1alpha hypoxic induction in the cells, suggesting involvement of
      mitochondria in regulation of HIF-1alpha accumulation during hypoxia. Regulation
      of HIF-1alpha by NO is an additional important mechanism by which NO might
      modulate cellular responses to hypoxia in mammalian cells.

PMID- 12055087
TI  - Force generation, but not myosin ATPase activity, declines with age in rat muscle
      fibers.
AB  - We tested the hypothesis that age-associated decline in muscle function is
      related to a change in myosin ATPase activity. Single, glycerinated
      semimembranosus fibers from young (8-12 mo) and aged (32-37 mo) Fischer 344 x
      Brown Norway male rats were analyzed simultaneously for force and myosin ATPase
      activity over a range of Ca2+ concentrations. Maximal force generation was ~20%
      lower in fibers from aged animals (P = 0.02), but myosin ATPase activity was not
      different between fibers from young and aged rats: 686 +/- 46 (n = 30) and 697 +/
      46 microM/s (n = 33) (P = 0.89). The apparent rate constant for the dissociation
      of strong-binding myosin from actin was calculated to be ~30% greater in fibers
      from aged animals (P = 0.03), indicating that the lower force produced by fibers
      from aged animals is due to a greater flux of myosin heads from the strong
      binding state to the weak-binding state during contraction. This is in agreement
      with our previous electron paramagnetic resonance experiments that showed a
      reduced fraction of myosin heads in the strong-binding state during a maximal
      isometric contraction in fibers from older rats.

PMID- 12055088
TI  - Bradykinin B1 receptor blocks PDGF-induced mitogenesis by prolonging ERK
      activation and increasing p27Kip1.
AB  - The mechanism by which the bradykinin B1 receptor (B1R) inhibits platelet-derived
      growth factor (PDGF)-stimulated proliferation was investigated in cultured rat
      mesenteric arterial smooth muscle cells. The B1R agonist des-Arg9-bradykinin
      (DABK) was found to inhibit PDGF-mediated activation of the cyclin E-cyclin
      dependent kinase 2 (Cdk2) complex and to prevent hyperphosphorylation of
      retinoblastoma protein. DABK did not inhibit upregulation of cyclin E expression
      but increased expression of the Cdk2 inhibitor p27Kip1 and the association of
      p27Kip1 with the cyclin E-Cdk2 complex. In addition, DABK inhibited the PDGF
      stimulated expression of cyclin D that would otherwise siphon p27Kip1 away from
      inhibition of cyclin E-Cdk2. The signaling mechanism by which DABK regulated
      p27Kip1 was explored. DABK was found to stimulate the activity of mitogen
      activated protein kinase kinase (MEK) and extracellular signal-regulated kinase
      (ERK) and to prolong activation of MEK and ERK by PDGF. Inhibition of ERK
      activation with the MEK inhibitors PD-98059 and U-0126 as well as the Src family
      kinase inhibitor PP2 completely blocked the effect of DABK to increase p27Kip1
      and partially reversed the DABK-mediated inhibition of PDGF-stimulated
      proliferation. These studies demonstrate that the B1R inhibits PDGF-stimulated
      mitogenesis in part by prolonged activation of ERK leading to increased
      expression of p27Kip1.

PMID- 12055090
TI  - Fibroblasts cocultured with keloid keratinocytes: normal fibroblasts secrete
      collagen in a keloidlike manner.
AB  - Keloid scars represent a pathological response to cutaneous injury, reflecting a
      new set point between synthesis and degradation biased toward extracellular
      matrix (ECM) collagen accumulation. Using a serum-free two-chamber coculture
      model, we recently demonstrated a significant increase in normal fibroblast
      proliferation when cocultured with keloid-derived keratinocytes. We hypothesized
      that similar keratinocyte-fibroblast interactions might influence fibroblast
      collagen production and examined conditioned media and cell lysate from coculture
      for collagen I and III production by Western blot, allied with Northern analysis
      for procollagen I and III mRNA. Normal fibroblasts cocultured with keloid
      keratinocytes produced increased soluble collagen I and III with a corresponding
      increase in procollagen I and III mRNA transcript levels. This was associated
      with decreased insoluble collagen from cell lysate. When keloid fibroblasts were
      cocultured with keloid keratinocytes, both soluble and insoluble collagen were
      increased with associated procollagen III mRNA upregulation. Transmission
      electron microscopy of normal fibroblasts cocultured with keloid keratinocytes
      showed an ECM appearance similar to in vivo keloid tissue, an appearance not seen
      when normal fibroblasts were cocultured with normal keratinocytes.

PMID- 12055089
TI  - Multiple signaling pathways mediate LIF-induced skeletal muscle satellite cell
      proliferation.
AB  - There are many known growth factors/cytokines that induce skeletal muscle
      satellite cell proliferation. Currently, the signaling mechanisms in which these
      growth factors/cytokines activate satellite cell proliferation are not completely
      understood. Here, we sought to determine signaling mechanisms by which leukemia
      inhibitory factor (LIF) induces satellite cell proliferation in culture. First,
      we confirmed that LIF induces proliferation of C2C12 immortalized myoblasts and
      cultured primary rat satellite cells. In addition, we also found that this
      increase in proliferation can be inhibited by incubation of the cells in
      tyrphostin AG 490, a specific inhibitor of Janus-activated kinase (JAK) 2
      activity. Furthermore, we also found that incubation of the cells at various time
      points with LIF (10 ng/ml) induces a significant, transient increase in JAK2
      phosphorylation, signal transducers and activators of transcription (STAT3)
      phosphorylation, and STAT3 transcriptional activity. Increases in the STAT3
      sensitive endogenous SOC3 protein followed these transient increases in STAT3
      activation. In addition, AG 490 inhibited the increase in STAT3 phosphorylation.
      Finally, LIF did not change the phosphorylation status of extracellular signal
      regulated protein kinase (ERK)1/2 or affect the phosphorylation status of
      Akt/protein kinase B. However, LY-294002, an inhibitor of phosphoinositide 3
      kinase, blocked LIF-induced proliferation of satellite cells. These data suggest
      that LIF induces satellite cell proliferation by activation of the JAK2-STAT3
      signaling pathway, suggesting that this may be an important pathway in muscle
      growth and/or hypertrophy.

PMID- 12055091
TI  - Modulation of cardiac PIP2 by cardioactive hormones and other physiologically
      relevant interventions.
AB  - Phosphatidylinositol 4,5-bisphosphate (PIP2) affects profoundly several cardiac
      ion channels and transporters, and studies of PIP2-sensitive currents in excised
      patches suggest that PIP2 can be synthesized and broken down within 30 s. To test
      when, and if, total phosphatidylinositol 4-phosphate (PIP) and PIP(2) levels
      actually change in intact heart, we used a new, nonradioactive HPLC method to
      quantify anionic phospholipids. Total PIP and PIP2 levels (10-30 micromol/kg wet
      weight) do not change, or even increase, with activation of
      Galpha(q)/phospholipase C (PLC)-dependent pathways by carbachol (50 microM),
      phenylephrine (50 microM), and endothelin-1 (0.3 microM). Adenosine (0.2 mM) and
      phorbol 12-myristate 13-acetate (1microM) both cause 30% reduction of PIP2 in
      ventricles, suggesting that diacylglycerol (DAG)-dependent mechanisms negatively
      regulate cardiac PIP2. PIP2, but not PIP, increases reversibly by 30% during
      electrical stimulation (2 Hz for 5 min) in guinea pig left atria; the increase is
      blocked by nickel (2 mM). Both PIP and PIP2 increase within 3 min in hypertonic
      solutions, roughly in proportion to osmolarity, and similar effects occur in
      multiple cell lines. Inhibitors of several volume-sensitive signaling mechanisms
      do not affect these responses, suggesting that PIP2 metabolism might be sensitive
      to membrane tension, per se.

PMID- 12055092
TI  - C2C12 myoblast/osteoblast transdifferentiation steps enhanced by epigenetic
      inhibition of BMP2 endocytosis.
AB  - We investigated the modulation of critical transcriptional steps of C2C12
      myoblast/osteoblast transdifferentiation triggered by the bone morphogenetic
      protein 2 (BMP2) signaling protein, in response to epigenetic inhibition of the
      endocytotic internalization of exogenous BMP2. BMP2 endocytosis was inhibited
      chemically with polyethylene glycol-50 (PEG-Chol) and cyclodextrin and
      mechanically by mild hyposmotic treatment. BMP2-dependent nuclear translocation
      of the mother against Dpp (Smad1) transcription factor was ten times faster if
      BMP2 endocytosis was inhibited. Smad1-dependent expression of the JunB gene, the
      first transcriptional step in myoblast dedifferentiation, was increased by a
      factor of three to four. JunB-dependent levels of myogenin repression, one of the
      critical markers of terminal myoblastic differentiation, was amplified by a
      factor of three. Smad1-dependent levels of alkaline phosphatase expression, one
      of the C2C12 osteoblast differentiation markers, were 3.5 to 5 times higher. The
      same behavior was observed for osteopontin, the other C2C12 osteoblast
      differentiation marker. These results suggest that the cell genome could "sense"
      tissue mechanical deformations by mechanical inhibition of signaling protein
      endocytosis, thereby translating mechanical strains into transcription events
      involved in cell differentiation.

PMID- 12055093
TI  - Mechanisms of leptin secretion from white adipocytes.
AB  - The mechanisms regulating leptin secretion were investigated in isolated rat
      white adipocytes. Insulin (1-100 nM) linearly stimulated leptin secretion from
      incubated adipocytes for at least 2 h. The adrenergic agonists norepinephrine,
      isoproterenol (two nonselective beta-agonists), or CL-316243 (potent beta3) all
      inhibited insulin (10 nM)-stimulated leptin release. The inhibitory effects of
      norepinephrine and isoproterenol could be reversed not only by the nonselective
      antagonist propranolol but also by the selective antagonists ICI-89406 (beta1) or
      ICI-118551 (beta2), the beta2-antagonist being less effective than the beta1.
      Insulin-stimulated leptin secretion could also be inhibited by a series of agents
      increasing intracellular cAMP levels, such as lipolytic hormones (ACTH and
      thyrotropin-stimulating hormone), various nonhydrolyzable cAMP analogs, pertussis
      toxin, forskolin, methylxanthines (caffeine, theophylline, IBMX), and specific
      inhibitors of phosphodiesterase III (imazodan, milrinone, and amrinone).
      Significantly, antilipolytic agents other than insulin (adenosine, nicotinic
      acid, acipimox, and orthovanadate) did not mimic the acute stimulatory effects of
      insulin on leptin secretion under these conditions. We conclude that
      norepinephrine specifically inhibits insulin-stimulated leptin secretion not only
      via the low-affinity beta3-adrenoceptors but also via the high-affinity
      beta1/beta2-adrenoceptors. Moreover, it is suggested that 1) activation of
      phosphodiesterase III by insulin represents an important metabolic step in
      stimulation of leptin secretion, and 2) lipolytic hormones competitively
      counterregulate the stimulatory effects of insulin by activating the adenylate
      cyclase system.

PMID- 12055094
TI  - ET-1 stimulates ERK signaling pathway through sequential activation of PKC and
      Src in rat myometrial cells.
AB  - In this study, we analyzed in rat myometrial cells the signaling pathways
      involved in the endothelin (ET)-1-induced extracellular signal-regulated kinase
      (ERK) activation required for the induction of DNA synthesis. We found that
      inhibition of protein kinase C (PKC) by Ro-31-8220 abolished ERK activation.
      Inhibition of phospholipase C (PLC) by U-73122 or of phosphoinositide (PI) 3
      kinase by wortmannin partially reduced ERK activation. A similar partial
      inhibition was observed after treatment with pertussis toxin or PKC
      downregulation by phorbol ester treatment. The effect of wortmannin was additive
      with that produced by PKC downregulation but not with that due to pertussis
      toxin. These results suggest that both diacylglycerol-sensitive PKC, activated by
      PLC products, and diacylglycerol-insensitive PKC, possibly activated by a G(i)-PI
      3-kinase-dependent process, are involved in ET-1-induced ERK activation. These
      two pathways were found to be activated mainly through the ET(A) receptor
      subtype. ET-1 and phorbol ester stimulated Src activity in a PKC-dependent
      manner, both responses being abolished in the presence of Ro-31-8220. Inhibition
      of Src kinases by PP1 abrogated phorbol ester- and ET-1-induced ERK activation.
      Finally, ET-1 activated Ras in a PP1- and Ro-31-8220-sensitive manner.
      Altogether, our results indicate that ET-1 induces ERK activation in rat
      myometrial cells through the sequential stimulation of PKC, Src, and Ras.

PMID- 12055095
TI  - Rac1, but not RhoA, signaling protects epithelial adherens junction assembly
      during ATP depletion.
AB  - Rho family GTPase signaling regulates actin cytoskeleton and junctional complex
      assembly. Our previous work showed that RhoA signaling protects tight junctions
      from damage during ATP depletion. Here, we examined whether RhoA GTPase signaling
      protects adherens junction assembly during ATP depletion. Despite specific RhoA
      signaling- and ATP depletion-induced effects on adherens junction assembly, RhoA
      signaling did not alter adherens junction disassembly rates during ATP depletion.
      This shows that RhoA signaling specifically protects tight junctions from damage
      during ATP depletion. Rac1 GTPase signaling also regulates adherens junction
      assembly and therefore may regulate adherens junction assembly during ATP
      depletion. Indeed, we found that Rac1 signaling protects adherens junctions from
      damage during ATP depletion. Adherens junctions are regulated by various GTPases,
      including RhoA and Rac1, but adherens junctions are specifically protected by
      Rac1 signaling.

PMID- 12055096
TI  - Mitochondrial K(ATP) channel openers activate the ERK kinase by an oxidant
      dependent mechanism.
AB  - Extracellular signal-regulated kinases (ERKs) are key regulatory proteins that
      mediate cell survival, proliferation, and differentiation. Reactive oxygen
      species (ROS) may play a role in activation of the ERK pathway. Because
      mitochondria are a major source of ROS, we investigated whether mitochondria
      derived ROS play a role in ERK activation. Diazoxide, a potent mitochondrial ATP
      sensitive K+ (K(ATP)) channel opener, is known to depolarize the mitochondrial
      membrane potential and cause a reversible oxidation of respiratory chain
      flavoproteins, thus increasing mitochondrial ROS production. Using THP-1 cells as
      a model, we postulated that opening mitochondrial K(ATP) channels would increase
      production of ROS and, thereby, regulate the activity of the ERK kinase. We found
      that opening mitochondrial K(ATP) channels by diazoxide induced production of ROS
      as determined by an increased rate of dihydroethidium and dichlorofluorescein
      fluorescence. This increased production of ROS was associated with increased
      phosphorylation of ERK kinase in a time-dependent fashion. The MEK inhibitors PD
      98059 and U-0126 blocked ERK activation mediated by diazoxide. N-acetylcysteine,
      but not diphenyleneiodonium, attenuated ERK activation mediated by diazoxide.
      Adenovirus-mediated overexpression of manganese superoxide dismutase, which is
      expressed in mitochondria, decreased the rate of dihydroethidium oxidation as
      well as ERK activation. We conclude that mitochondrial K(ATP) channel openers
      trigger ERK activation via mitochondria-derived ROS.

PMID- 12055097
TI  - Phosphatidylinositol 3-kinase-dependent, MEK- independent proliferation in
      response to CaR activation.
AB  - Although ovarian surface epithelial (OSE) cells are responsible for the majority
      of ovarian tumors, we know relatively little about the pathway(s) that is
      responsible for regulating their proliferation. We found that
      phosphatidylinositol 3-kinase (PI3K) is activated in OSE cells in response to
      elevated extracellular calcium, and the PI3K inhibitors wortmannin and LY-294002
      inhibited extracellular signal-regulated kinase (ERK) activation by approximately
      75%, similar to effects of the mitogen-activated protein kinase/ERK kinase
      inhibitor PD-98059. However, in assays of proliferation, we found that PD-98059
      inhibited proliferation by approximately 50%, whereas wortmannin inhibited >90%
      of the proliferative response to elevated calcium. Expression of a dominant
      negative PI3K totally inhibited ERK activation in response to calcium. These
      results demonstrate that ERK activation cannot account for the full proliferative
      effect of elevated calcium in OSE cells and suggest the presence of an ERK
      independent, PI3K-dependent component in the proliferative response.

PMID- 12055099
TI  - Role of nitric oxide synthase isoforms in glucose-stimulated insulin release.
AB  - The role of islet constitutive nitric oxide synthase (cNOS) in insulin-releasing
      mechanisms is controversial. By measuring enzyme activities and protein
      expression of NOS isoforms [i.e., cNOS and inducible NOS (iNOS)] in islets of
      Langerhans cells in relation to insulin secretion, we show that glucose dose
      dependently stimulates islet activities of both cNOS and iNOS, that cNOS-derived
      nitric oxide (NO) strongly inhibits glucose-stimulated insulin release, and that
      short-term hyperglycemia in mice induces islet iNOS activity. Moreover, addition
      of NO gas or an NO donor inhibited glucose-stimulated insulin release, and
      different NOS inhibitors effected a potentiation. These effects were evident also
      in K+-depolarized islets in the presence of the ATP-sensitive K+ channel opener
      diazoxide. Furthermore, our results emphasize the necessity of measuring islet
      NOS activity when using NOS inhibitors, because certain concentrations of certain
      NOS inhibitors might unexpectedly stimulate islet NO production. This is shown by
      the observation that 0.5 mmol/l of the NOS inhibitor N(G)-monomethyl-L-arginine
      (L-NMMA) stimulated cNOS activity in parallel with an inhibition of the first
      phase of glucose-stimulated insulin release in perifused rats islets, whereas 5.0
      mmol/l of L-NMMA markedly suppressed cNOS activity concomitant with a great
      potentiation of the insulin secretory response. The data strongly suggest, but do
      not definitely prove, that glucose indeed has the ability to stimulate both cNOS
      and iNOS in the islets and that NO might serve as a negative feedback inhibitor
      of glucose-stimulated insulin release. The results also suggest that
      hyperglycemia-evoked islet NOS activity might be one of multiple factors involved
      in the impairment of glucose-stimulated insulin release in type II diabetes
      mellitus.

PMID- 12055098
TI  - Cytokine response to eccentric exercise in young and elderly humans.
AB  - To examine the plasma interleukin (IL)-6 response in elderly (E) and young (Y)
      humans, 10 E and 10 Y subjects completed 60 min of eccentric lower limb exercise
      at the same relative oxygen uptake. Plasma IL-6 was measured before, immediately
      after, and 5 days into recovery from exercise, as were the biochemical markers of
      muscle damage, creatine kinase (CK), and myoglobin. In both groups, IL-6
      increased (P < 0.05) immediately after exercise and peaked 4 h after exercise at
      4.35 +/- 1.7 vs. 5.05 +/- 3.17 pg/ml for E and Y subjects, respectively. However,
      the increase in IL-6 in both groups was modest relative to the increases in CK
      peaking at 539 +/- 413 vs. 10,301 +/- 5,863 U/l for E and Y subjects,
      respectively. In addition, the increase in IL-6 was less pronounced (P < 0.05) in
      E subjects compared with Y subjects. These results suggest that IL-6 increases
      progressively after eccentric exercise, suggesting that this increase is related
      to muscle damage. However, the modest increase in IL-6, despite large increases
      in CK, suggests that the IL-6 response to muscle damage does not make an
      important contribution to the large increase in IL-6 observed during concentric
      exercise of long duration. Our data also suggest that aging may be associated
      with impaired repair mechanisms for exercise-induced muscle damage.

PMID- 12055100
TI  - Human nongastric H+-K+-ATPase: transport properties of ATP1al1 assembled with
      different beta-subunits.
AB  - To investigate whether nongastric H+-K+-ATPases transport Na+ in exchange for K+
      and whether different beta-isoforms influence their transport properties, we
      compared the functional properties of the catalytic subunit of human nongastric
      H+-K+-ATPase, ATP1al1 (AL1), and of the Na+-K+-ATPase alpha1-subunit (alpha1)
      expressed in Xenopus oocytes, with different beta-subunits. Our results show that
      betaHK and beta1-NK can produce functional AL1/beta complexes at the oocyte cell
      surface that, in contrast to alpha1/beta1 NK and alpha1/betaHK complexes, exhibit
      a similar apparent K+ affinity. Similar to Na+-K+-ATPase, AL1/beta complexes are
      able to decrease intracellular Na+ concentrations in Na+-loaded oocytes, and
      their K+ transport depends on intra- and extracellular Na+ concentrations.
      Finally, controlled trypsinolysis reveals that beta-isoforms influence the
      protease sensitivity of AL1 and alpha1 and that AL1/beta complexes, similar to
      the Na+-K+-ATPase, can undergo distinct K+-Na+- and ouabain-dependent
      conformational changes. These results provide new evidence that the human
      nongastric H+-K+-ATPase interacts with and transports Na+ in exchange for K+ and
      that beta-isoforms have a distinct effect on the overall structural integrity of
      AL1 but influence its transport properties less than those of the Na+-K+-ATPase
      alpha-subunit.

PMID- 12055102
TI  - TIMAP, a novel CAAX box protein regulated by TGF-beta1 and expressed in
      endothelial cells.
AB  - Representational difference analysis of the glomerular endothelial cell response
      to transforming growth factor-beta1 (TGF-beta1) revealed a novel gene, TIMAP (TGF
      beta-inhibited membrane-associated protein), which contains 10 exons and maps to
      human chromosome 20.q11.22. By Northern blot, TIMAP mRNA is highly expressed in
      all cultured endothelial and hematopoietic cells. The frequency of the TIMAP SAGE
      tag is much greater in endothelial cell SAGE databases than in nonendothelial
      cells. Immunofluorescence studies of rat tissues show that anti-TIMAP antibodies
      localize to vascular endothelium. TGF-beta1 represses TIMAP through a protein
      synthesis- and histone deacetylase-dependent process. The TIMAP protein contains
      five ankyrin repeats, a protein phosphatase-1 (PP1)-interacting domain, a COOH
      terminal CAAX box, a domain arrangement similar to that of MYPT3, and a PP1
      inhibitor. A green fluorescent protein-TIMAP fusion protein localized to the
      plasma membrane in a CAAX box-dependent fashion. Hence, TIMAP is a novel gene
      highly expressed in endothelial and hematopoietic cells and regulated by TGF
      beta1. On the basis of its domain structure, TIMAP may serve a signaling
      function, potentially through interaction with PP1.

PMID- 12055101
TI  - Human trabecular meshwork cell volume regulation.
AB  - The volume of certain subpopulations of trabecular meshwork (TM) cells may modify
      outflow resistance of aqueous humor, thereby altering intraocular pressure. This
      study examines the contribution that Na+/H+, Cl-/HCO exchange, and K+-Cl- efflux
      mechanisms have on the volume of TM cells. Volume, Cl- currents, and
      intracellular Ca2+ activity of cultured human TM cells were studied with calcein
      fluorescence, whole cell patch clamping, and fura 2 fluorescence, respectively.
      At physiological bicarbonate concentration, the selective Na+/H+ antiport
      inhibitor dimethylamiloride reduced isotonic cell volume. Hypotonicity triggered
      a regulatory volume decrease (RVD), which could be inhibited by the Cl- channel
      blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), the K+ channel blockers
      Ba2+ and tetraethylammonium, and the K+-Cl- symport blocker
      [(dihydroindenyl)oxy]alkanoic acid. The fluid uptake mechanism in isotonic
      conditions was dependent on bicarbonate; at physiological levels, the Na+/H+
      exchange inhibitor dimethylamiloride reduced cell volume, whereas at low levels
      the Na+-K+-2Cl- symport inhibitor bumetanide had the predominant effect. Patch
      clamp measurements showed that hypotonicity activated an outwardly rectifying,
      NPPB-sensitive Cl- channel displaying the permeability ranking Cl- >
      methylsulfonate > aspartate. 2,3-Butanedione 2-monoxime antagonized actomyosin
      activity and both increased baseline [Ca2+] and abolished swelling-activated
      increase in [Ca2+], but it did not affect RVD. Results indicate that human TM
      cells display a Ca2+-independent RVD and that volume is regulated by swelling
      activated K+ and Cl- channels, Na+/H+ antiports, and possibly K+-Cl- symports in
      addition to Na+-K+-2Cl- symports.

PMID- 12055103
TI  - Channel-mediated water movement across enclosed or perfused mouse intrahepatic
      bile duct units.
AB  - We previously reported the development of reproducible techniques for isolating
      and perfusing intact intrahepatic bile duct units (IBDUs) from rats. Given the
      advantages of transgenic and knockout mice for exploring ductal bile formation,
      we report here the adaptation of those techniques to mice and their initial
      application to the study of water transport across mouse intrahepatic biliary
      epithelia. IBDUs were isolated from livers of normal mice by microdissection
      combined with enzymatic digestion. After culture, isolated IBDUs sealed to form
      intact, polarized compartments, and a microperfusion system employing those
      isolated IBDUs developed. A quantitative image analysis technique was used to
      observe a rapid increase of luminal area when sealed IBDUs were exposed to a
      series of inward osmotic gradients reflecting net water secretion; the choleretic
      agonists secretin and forskolin also induced water secretion into IBDUs. The
      increase of IBDU luminal area induced by inward osmotic gradients and choleretic
      agonists was reversibly inhibited by HgCl2, a water channel inhibitor. With the
      use of a quantitative epifluorescence technique in perfused mouse IBDUs, a high
      osmotic water permeability (P(f) = 2.5-5.6 x 10(-2) cm/s) was found in response
      to osmotic gradients, further supporting the presence of water channels. These
      findings suggest that, as in the rat, water transport across intrahepatic biliary
      epithelia in mice is water channel mediated.

PMID- 12055104
TI  - Differential requirement for NF-kappaB-inducing kinase in the induction of NF
      kappaB by IL-1beta, TNF-alpha, and Fas.
AB  - In this study, we examined the role of the nuclear factor-kappaB (NF-kappaB)
      inducing kinase (NIK) in distinct signaling pathways leading to NF-kappaB
      activation. We show that a dominant-negative form of NIK (dnNIK) delivered by
      adenoviral (Ad5dnNIK) vector inhibits Fas-induced IkappaBalpha phosphorylation
      and NF-kappaB-dependent gene expression in HT-29 and HeLa cells. Interleukin (IL)
      1beta- and tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activation
      and kappaB-dependent gene expression are inhibited in HeLa cells but not in
      Ad5dnNIK-infected HT-29 cells. Moreover, Ad5dnNIK failed to sensitize HT-29 cells
      to TNF-alpha-induced apoptosis at an early time point. However, cytokine- and Fas
      induced signals to NF-kappaB are finally integrated by the IkappaB kinase (IKK)
      complex, since IkappaBalpha phosphorylation, NF-kappaB DNA binding activity, and
      IL-8 gene expression were strongly inhibited in HT-29 and HeLa cells
      overexpressing dominant-negative IKKbeta (Ad5dnIKKbeta). Our findings support the
      concept that cytokine signaling to NF-kappaB is redundant at the level of NIK. In
      addition, this study demonstrates for the first time the critical role of NIK and
      IKKbeta in Fas-induced NF-kappaB signaling cascade.

PMID- 12055105
TI  - Apical Na+/H+ exchange near the base of mouse colonic crypts.
AB  - Colonic crypts can absorb fluid, but the identity of the absorptive transporters
      remains speculative. Near the crypt base, the epithelial cells responsible for
      vectorial transport are relatively undifferentiated and often presumed to mediate
      only Cl- secretion. We have applied confocal microscopy in combination with an
      extracellular fluid marker [Lucifer yellow (LY)] or a pH-sensitive dye (2',7'
      bis(2-carboxyethyl)-5(6)-carboxyfluorescein) to study mouse colonic crypt
      epithelial cells directly adjacent to the crypt base within an intact mucosal
      sheet. Measurements of intracellular pH report activation of colonocyte Na+/H+
      exchange in response to luminal or serosal Na+. Studies with LY demonstrate the
      presence of a paracellular fluid flux, but luminal Na+ does not activate Na+/H+
      exchange in the nonepithelial cells of the lamina propria, and studies with LY
      suggest that the fluid bathing colonocyte basolateral membranes is rapidly
      refreshed by serosal perfusates. The apical Na+/H+ exchange in crypt colonocytes
      is inhibited equivalently by luminal 20 microM ethylisopropylamiloride and 20
      microM HOE-694 but is not inhibited by luminal 20 microM S-1611. Immunostaining
      reveals the presence of epitopes from NHE1 and NHE2, but not NHE3, in epithelial
      cells near the base of colonic crypts. Comparison of apical Na+/H+ exchange
      activity in the presence of Cl- with that in the absence of Cl- (substitution by
      gluconate or nitrate) revealed no evidence of the Cl--dependent Na+/H+ exchange
      that had been previously reported as the sole apical Na+/H+ exchange activity in
      the colonic crypt. Results suggest the presence of an apical Na+/H+ exchanger
      near the base of crypts with functional attributes similar to those of the cloned
      NHE2 isoform.

PMID- 12055106
TI  - Generation of a cell line with smooth muscle phenotype from hypertrophied urinary
      bladder.
AB  - We have established a cell line from hypertrophied rabbit urinary bladder smooth
      muscle (SM) that stably expresses SM myosin (SMM). These cells, termed BSM, are
      spindle shaped and form swirls, similar to the "hills and valleys" described for
      cultured aortic SM cells. Western blotting revealed that BSM expresses the amino
      terminal SMM heavy chain isoform SM-B, the carboxy-terminal SM1 and SM2 isoforms,
      and SM alpha-actin. In addition, they express cGMP-dependent protein kinase G,
      made by contractile SM cells in vitro but not by noncontractile cells
      synthesizing extracellular matrix. Immunofluorescence studies indicate a
      homogeneous population of cells expressing alpha-actin and SMM, including the SM
      B isoform, and karyotyping demonstrates a stable 4N chromosomal pattern. These
      cells also express calcium-dependent myosin light chain kinase and phosphatase
      activity and contract in response to the muscarinic agonist bethanechol. To our
      knowledge, BSM is the first visceral SM cell line that expresses the SM-B isoform
      and might serve as a useful model to study the transcriptional regulation of
      tissue-specific SMM isoforms in differentiation and pathological SM.

PMID- 12055107
TI  - Cavum septi pellucidi--a reason to ban boxers?

PMID- 12055109
TI  - Physical activity and all cause mortality in women: a review of the evidence.
AB  - A computer assisted literature search was performed (Medline, 1966-2000) to
      examine the association of physical activity with all cause mortality in women.
      It was concluded that, by adhering to current guidelines for physical activity
      and expending about 4200 kJ of energy a week, women can postpone mortality. The
      magnitude of benefit experienced by women is similar to that seen in men.

PMID- 12055110
TI  - Ultrasound guided sclerosis of neovessels in painful chronic Achilles tendinosis:
      pilot study of a new treatment.
AB  - BACKGROUND: The mechanism that causes pain in chronic Achilles tendinosis is not
      known. However, high resolution colour Doppler ultrasound has shown that
      neovascularisation may be involved. OBJECTIVE: To investigate if sclerosing the
      neovessels would affect the level of tendon pain. METHODS: The effect of colour
      Doppler ultrasound guided injection of a sclerosing agent, polidocanol, against
      neovessels was studied in 10 patients (seven men and three women, mean age 55
      years) with painful chronic mid-portion Achilles tendinosis. RESULTS: Eight
      patients were satisfied with the results of treatment. There was significantly
      reduced pain during activity (reported on a visual analogue scale (VAS)) and no
      remaining neovascularisation after an average of two injections. Two patients
      were not satisfied, and neovascularisation remained. At the six month follow up,
      the same eight patients remained satisfied and could perform Achilles tendon
      loading activities as desired. Their VAS score had decreased from 74 before
      treatment to 8 (p<0.01). CONCLUSIONS: Sclerosing neovessels appears to be an
      effective treatment for painful chronic Achilles tendinosis, suggesting that
      neovessels play a key part in causing chronic tendon pain.

PMID- 12055111
TI  - Surgical treatment for chronic Achilles tendinopathy: a prospective seven month
      follow up study.
AB  - OBJECTIVE: To prospectively assess the early results of surgical treatment of
      chronic Achilles tendinopathy. METHODS: This seven month prospective follow up
      study assessed the short term results of surgical treatment of chronic Achilles
      tendinopathy and compared the subjective and functional outcome of patients with
      Achilles tendinopathy without a local intratendinous lesion (group A) with that
      of similar patients with such a lesion (group B). Forty two of the initial 50
      patients were examined before surgery and after the seven month follow up.
      Evaluation included an interview, subjective evaluation, clinical tests, and a
      performance test. RESULTS: At the follow up, physical activity was fully restored
      in 28 of the 42 patients (67%), and 35 patients (83%) were asymptomatic or had
      only mild pain during strenuous exercise. In clinical tests, significant
      improvements were observed in climbing up and down stairs and the rising on the
      toes test. Surgical treatment also seemed to be successful from the total test
      score, which was excellent or good in 35 patients, compared with before surgery
      when it was excellent or good in one patient only. Patients in group A fared
      better than those in group B, whether evaluated by recovery of physical activity
      after surgery (88% v 54%) or the complication rate (6% v 27%). CONCLUSIONS:
      Surgical treatment of chronic Achilles tendinopathy gives good and acceptable
      short term results. A lower complication rate and a trend to better recovery was
      observed in patients with peritendinous adhesions only than in those with
      peritendinous adhesions combined with an intratendinous lesion.

PMID- 12055113
TI  - Randomised, controlled walking trials in postmenopausal women: the minimum dose
      to improve aerobic fitness?
AB  - BACKGROUND: The American College of Sports Medicine recommends 20-60 minutes of
      aerobic exercise three to five days a week at an intensity of 40/50-85% of
      maximal aerobic power (VO(2)MAX) reserve, expending a total of 700-2000 kcal
      (2.93-8.36 MJ) a week to improve aerobic power and body composition. OBJECTIVE:
      To ascertain the minimum effective dose of exercise. METHODS: Voluntary, healthy,
      non-obese, sedentary, postmenopausal women (n = 121), 48-63 years of age, were
      randomised to four low dose walking groups or a control group; 116 subjects
      completed the study. The exercise groups walked five days a week for 24 weeks
      with the following intensity (% of VO(2)MAX) and energy expenditure (kcal/week):
      group W1, 55%/1500 kcal; group W2, 45%/1500 kcal; group W3, 55%/1000 kcal; group
      W4, 45%/1000 kcal. VO(2)MAX was measured in a direct maximal treadmill test.
      Submaximal aerobic fitness was estimated as heart rates at submaximal work levels
      corresponding to 65% and 75% of the baseline VO(2)MAX. The body mass index (BMI)
      was calculated and percentage of body fat (F%) estimated from skinfolds. RESULTS:
      The net change (the differences between changes in each exercise group and the
      control group) in VO(2)MAX was 2.9 ml/min/kg (95% confidence interval (CI) 1.5 to
      4.2) in group W1, 2.6 ml/min/kg (95% CI 1.3 to 4.0) in group W2, 2.4 ml/min/kg
      (95% CI 0.9 to 3.8) in group W3, and 2.2 ml/min/kg (95% CI 0.8 to 3.5) in group
      W4. The heart rates in standard submaximal work decreased 4 to 8 beats/min in all
      the groups. There was no change in BMI, but the F% decreased by about 1% unit in
      all the groups. CONCLUSIONS: Walking (for 24 weeks) at moderate intensity 45% to
      55% of VO(2)MAX, with a total weekly energy expenditure of 1000-1500 kcal,
      improves VO(2)MAX and body composition of previously sedentary, non-obese,
      postmenopausal women. This dose of exercise apparently approaches the minimum
      effective dose.

PMID- 12055112
TI  - Escin/diethylammonium salicylate/heparin combination gels for the topical
      treatment of acute impact injuries: a randomised, double blind, placebo
      controlled, multicentre study.
AB  - OBJECTIVES: To investigate the clinical efficacy and safety of escin-containing
      gels in the topical treatment of blunt impact injuries. METHODS: Competitors in
      soccer, handball, or karate competitions were enrolled within two hours of
      sustaining a strain, sprain, or contusion and treated three times with the trial
      gel within a period of eight hours. Patients were randomised to three parallel
      groups consisting of two active treatment gels, containing escin (1% or 2%), 5%
      diethylammonium salicylate, and 5000 IU heparin, or placebo gel. Tenderness
      produced by pressure was measured at 0 (baseline), 1, 2, 3, 4, 6, and 24 hours
      after enrollment (within two hours of the injury). Tenderness was defined as the
      amount of pressure (measured by a calibrated caliper at the centre of the injury)
      that first produced a pain reaction as reported by the patient. RESULTS: A total
      of 158 patients were enrolled; 156 were evaluated in the intention to treat
      analysis. The primary efficacy variable was the area under the curve for
      tenderness over a six hour period. The gel preparations containing 1% and 2%
      escin were significantly more effective (a priori ordered hypotheses testing
      controlling the multiple alpha = 5% significance level) than placebo (p(1) =
      0.0001 and p(2) = 0.0002 respectively). The treatment effects were 5.7 kp h/cm(2)
      (95% confidence interval (CI) 2.9 to 8.5) and 5.9 kilopond (kp) h/cm(2) (95% CI
      2.9 to 8.8) between 1% escin and placebo and between 2% escin and placebo
      respectively. These results were supported by secondary efficacy variables. The
      time to reach the baseline contralateral tenderness value (resolution of pain) at
      the injured site was shorter in the treatment groups than in the placebo group
      (p<0.0001). Both active gel preparations produced more rapid pain relief than the
      placebo gel. No relevant differences were detected between the two active gels.
      The safety and tolerability of the escin-containing gels were excellent.
      CONCLUSIONS: Escin/diethylammonium salicylate/heparin combination gel
      preparations are effective and safe for the treatment of blunt impact injuries.

PMID- 12055114
TI  - Effects of exercise on soluble transferrin receptor and other variables of the
      iron status.
AB  - BACKGROUND: Soluble transferrin receptor (sTfr) is a new marker of iron status
      and erythropoietic activity. It has been included in multivariable blood testing
      models for the detection of performance enhancing erythropoietin misuse in sport.
      OBJECTIVE: To evaluate the effect of different types and volumes of physical
      activity on sTfr concentration, variables of iron status (ferritin, transferrin,
      iron, and protein), and haematological indices. METHODS: Thirty nine subjects
      were divided into three groups: 1, untrained (n = 12); 2, moderately trained (n =
      14); 3, highly trained (n = 13, seven men, six women). Groups 1 and 2 carried out
      two exercise tests: an incremental running test until exhaustion (test A) and a
      45 minute constant speed running test at 70% VO(2)MAX (test B). Group 3 performed
      three days (women) or four days (men) of prolonged aerobic cycling exercise. The
      above variables together with haemoglobin and packed cell volume were analysed in
      venous blood samples before and after exercise. Changes in blood and plasma
      volume were estimated. RESULTS: sTfr levels were slightly increased in trained
      and untrained subjects immediately after test A. Test B and aerobic exercise had
      no significant effect on sTfr. Ferritin levels were increased after the
      laboratory tests for trained and untrained subjects and after prolonged aerobic
      exercise in male cyclists. Transferrin was increased significantly in trained and
      untrained subjects after both laboratory tests, but remained unchanged after
      prolonged exercise. Plasma and blood volumes were decreased after the laboratory
      tests but increased after aerobic exercise. No differences in the variables were
      observed between trained and untrained subjects with respect to response to
      exercise. CONCLUSION: The changes in sTfr and the variables of iron status can be
      mainly attributed to exercise induced changes in volume. Taking these limitations
      into account, sTfr can be recommended as a marker of iron deficiency in athletes.

PMID- 12055115
TI  - Evidence based medicine in clinical practice: how to advise patients on the
      influence of age on the outcome of surgical anterior cruciate ligament
      reconstruction: a review of the literature.
AB  - OBJECTIVE: To determine, using a literature search, whether patient age
      influences the outcome of surgical reconstruction of a torn anterior cruciate
      ligament. METHODS: Medline (1966 to present) was searched using the PubMed
      interface, Embase (1974 to present) using the Datastar system, and the Cochrane
      Library at the Update Software web site. Papers retrieved from the three
      databases were independently assessed by two reviewers using preliminary
      inclusion criteria. Reference lists of papers satisfying the preliminary criteria
      were then scanned and appropriate papers reviewed. Any new papers in turn had
      their reference lists scanned, this process continuing until no new papers were
      identified. Final inclusion criteria were then applied to all papers satisfying
      the preliminary inclusion criteria. RESULTS: The initial search identified 661
      papers. Exclusion of duplicates produced 536 unique papers. Medline contained
      445, Embase 185, and the Cochrane Library 31. Of the 536, 523 were assessed by
      abstract and 12 by full text; one paper was not retrieved. Application of the
      preliminary inclusion criteria produced 33 papers. Their reference lists
      contained 950 references. Scanning of these added six new papers to the dataset.
      These six had their reference lists assessed; no new papers were identified. Four
      of the 39 papers in the completed dataset satisfied the final inclusion criteria.
      There was wide variation in the total number of subjects in the four studies,
      ranging from 22 to 203 patients. The total number of different outcome measures
      was 17; only one measure was used by all four studies. None of the objective
      outcome measures showed any significant difference between age groups, and the
      subjective measures, which did show differences, were contradictory. A total of
      108 interlibrary loans were requested, by a full time researcher, at a total cost
      of 432.00 Irish pounds over a 10 week period. CONCLUSIONS: When advising patients
      on the outcome of anterior cruciate ligament reconstruction, age should not be
      considered in isolation. In the absence of relevant guidelines, meta-analyses, or
      systematic reviews, the application of evidence based medicine to clinical
      practice has significant resource implications.

PMID- 12055116
TI  - Effect of ethylene vinyl acetate (EVA) closed cell foam on transmitted forces in
      mouthguard material.
AB  - OBJECTIVES: To compare transmitted forces through ethylene vinyl acetate (EVA)
      mouthguard material and the same EVA material with gas inclusions in the form of
      a closed cell foam. METHOD: EVA mouthguard materials with and without foam gas
      inclusions and 4 mm thick were impacted with a constant force from an impact
      pendulum. Various porosity levels in the foam materials were produced by 1%, 5%,
      and 10% by weight foaming agent. The forces transmitted through the EVA after
      energy absorption by the test materials were measured with a force sensor and
      compared. RESULTS: Only minor non-significant differences in transmitted forces
      through the EVA with and without foam were shown. CONCLUSIONS: The inclusion of
      gas in the form of a closed cell foam in 4 mm thick EVA mouthguard materials did
      not improve the impact performance of the EVA mouthguard material.

PMID- 12055117
TI  - Benefits and risks of using local anaesthetic for pain relief to allow early
      return to play in professional football.
AB  - OBJECTIVE: To investigate the risks and benefits of the use of local anaesthetic
      in a descriptive case series from three professional football (rugby league and
      Australian football) teams. METHODS: Cases of local anaesthetic use (both
      injection and topical routes) and complications over a six year period were
      recorded. Complications were assessed using clinical presentation and also by
      recording all cases of surgery, incidences of players missing games or leaving
      the field through injury, and causes of player retirement. RESULTS: There were
      268 injuries for which local anaesthetic was used to allow early return to play.
      There were 11 minor and six major complications, although none of these were
      catastrophic or career ending. About 10% of players taking the field did so with
      the assistance of local anaesthetic. This rate should be considered in isolation
      and not seen to reflect standard practice by team doctors. CONCLUSIONS: The use
      of local anaesthetic in professional football may reduce the rates of players
      missing matches through injury, but there is the risk of worsening the injury,
      which should be fully explained to players. A procedure should only be used when
      both the doctor and player consider that the benefits outweigh the risks.

PMID- 12055118
TI  - The trunk muscles of elite oarsmen.
AB  - OBJECTIVES: To investigate the trunk strength of elite rowers and the impact of
      low back pain on these measures in order to determine if asymmetries or weakness
      were present. METHODS: Twenty two elite rowers were recruited: 13 reported
      previous low back pain, five current low back pain, and the remainder had no
      history of low back pain. All subjects were scanned during simulated rowing in an
      interventional open magnetic resonance imaging scanner. In each simulated rowing
      position, axial scans were obtained at the level of the L4-5 and L5-S1 disc
      interspace to determine the cross sectional area of the posterior trunk muscles.
      RESULTS: Considerable differences were observed between the three groups of
      rowers. In contrast with expectations and previous literature, the trunk muscles
      of rowers with low back pain had significantly larger cross sectional areas
      (p<0.001). No left/right asymmetries were observed and no differences between
      oarside and non-oarside in terms of muscle cross sectional area. CONCLUSION:
      These findings suggest that low back pain in rowers does not arise as a result of
      muscle weakness.

PMID- 12055120
TI  - Soccer specific aerobic endurance training.
AB  - BACKGROUND: In professional soccer, a significant amount of training time is used
      to improve players' aerobic capacity. However, it is not known whether soccer
      specific training fulfils the criterion of effective endurance training to
      improve maximal oxygen uptake, namely an exercise intensity of 90-95% of maximal
      heart rate in periods of three to eight minutes. OBJECTIVE: To determine whether
      ball dribbling and small group play are appropriate activities for interval
      training, and whether heart rate in soccer specific training is a valid measure
      of actual work intensity. METHODS: Six well trained first division soccer players
      took part in the study. To test whether soccer specific training was effective
      interval training, players ran in a specially designed dribbling track, as well
      as participating in small group play (five a side). Laboratory tests were carried
      out to establish the relation between heart rate and oxygen uptake while running
      on a treadmill. Corresponding measurements were made on the soccer field using a
      portable system for measuring oxygen uptake. RESULTS: Exercise intensity during
      small group play was 91.3% of maximal heart rate or 84.5% of maximal oxygen
      uptake. Corresponding values using a dribbling track were 93.5% and 91.7%. No
      higher heart rate was observed during soccer training. CONCLUSIONS: Soccer
      specific exercise using ball dribbling or small group play may be performed as
      aerobic interval training. Heart rate monitoring during soccer specific exercise
      is a valid indicator of actual exercise intensity.

PMID- 12055121
TI  - Exact moment of a gastrocnemius muscle strain captured on video.
AB  - A left gastrocnemius strain was sustained by an elite cricket batsman while he
      was taking off to run. The exact moment of injury, captured by a camera in the
      middle stump, appears to correspond to the sudden appearance of a deficit in the
      gastrocnemius muscle, seen through the player's trousers. The strain occurred
      when the entire body weight was on the left foot with the centre of mass well in
      front of the leg. The injury probably occurred close to the time when the
      gastrocnemius complex was moving from an eccentric to an isometric phase.

PMID- 12055122
TI  - Stress fracture of the hook of the hamate.
AB  - Fractures of the hook of the hamate have rarely been reported. They have usually
      resulted from blunt trauma or a sharp strike against the hamate hook while
      swinging a golf club, baseball bat, or tennis racquet. Patients present with
      acute onset of pain localised over the ulnar aspect of the wrist and reduction in
      grip strength. In the case reported here, the patient complained of gradual onset
      of pain on the ulnar aspect of the wrist after altering his grip for serving in
      tennis. Once the diagnosis was made, the fracture was treated conservatively and
      the patient made a complete recovery.

PMID- 12055123
TI  - Pectoralis major tendon ruptures: when to operate.
AB  - The treatment of pectoralis major tendon ruptures has been the subject of much
      debate. The classical history of the injury is forced abduction and external
      rotation. The cases of two patients (an amateur rugby union player and a
      recreational snowboarder) are reported. The diagnosis was made by clinical
      examination in both patients, and both were operated on more than two weeks after
      injury. After surgery and a graduated rehabilitation programme, both men were
      able to return to their sporting activities. These two cases highlight the
      advantage of operative management in this uncommon condition.

PMID- 12055124
TI  - Medicine at the 2000 Sydney Olympic Games: the New Zealand health team.

PMID- 12055125
TI  - Endothelial AT(2)-receptors: chicken or egg?

PMID- 12055126
TI  - AT(2) receptor-dependent vasodilation is mediated by activation of vascular kinin
      generation under flow conditions.
AB  - Physiological roles of angiotensin II type 2 receptor (AT(2)) are not well
      defined. This study was designed to investigate the mechanisms of AT(2)-dependent
      vascular relaxation by studying vasodilation in pressurized and perfused rat
      mesenteric arterial segments. Perfusion of angiotensin II in the presence of
      AT(1) antagonist elicited vascular relaxation, which was completely dependent on
      AT(2) receptors on endothelium. FR173657 (>1 microM), a bradykinin (BK) B(2)
      specific antagonist, significantly suppressed AT(2)-dependent vasodilation
      (maximum inhibition: 68.5% at 10 microM). Kininogen-deficient Brown Norway
      Katholiek rats showed a significant reduction in AT(2)-mediated vasodilatory
      response compared with normal wild-type Brown Norway rats. Indomethacin (>1
      microM), aprotinin (10 microM) and soybean trypsin inhibitor (10 microM) also
      reduced AT(2)-dependent vasodilation. Our results demonstrated that stimulation
      of AT(2) receptors caused a significant vasodilation through local production of
      BK in resistant arteries of rat mesentery in a flow-dependent manner. Such
      vasodilation counterbalances AT(1)-dependent vasoconstriction to regulate the
      vascular tone.

PMID- 12055127
TI  - Enzymatic activation of endothelial protease-activated receptors is dependent on
      artery diameter in human and porcine isolated coronary arteries.
AB  - Protease-activated receptor (PAR)-mediated vascular relaxations have been
      compared in coronary arteries of different diameters isolated from both humans
      and pigs. Thrombin, trypsin, and the PAR1-activating peptide, TFLLR, all caused
      concentration-dependent relaxation of both large (epicardial; approximately 2 mm
      internal diameter) and small (intramyocardial; approximately 200 microm internal
      diameter) human coronary arteries. EC(50) values for thrombin (0.006 u ml(-1) in
      epicardial, 1.69 u ml(-1) in intramyocardial) and trypsin (0.02 u ml(-1) in
      epicardial, 1.05 u ml(-1) in intramyocardial) were significantly (P<0.01) greater
      in intramyocardial arteries. By contrast, EC(50) values for TFLLR were not
      different between epicardial (0.35 microM) and intramyocardial (0.43 microM)
      arteries. In porcine coronary arteries, EC(50) values for relaxations to thrombin
      (0.03 u ml(-1) in epicardial 0.17 u ml(-1) in intramyocardial) were also
      significantly (P<0.01) greater in the smaller arteries. EC(50) values for both
      TFLLR and the PAR2-activating peptide, SLIGKV, were not different between the two
      different-sized pig coronary arteries. PAR1-immunoreactivity was localized to the
      endothelium of human epicardial and intramyocardial arteries and both PAR1- and
      PAR2-immunoreactivity was observed in endothelial cells of equivalent porcine
      arteries. These findings indicate that enzymatic activation of endothelial cell
      PARs in human (PAR1) and porcine (PAR1 and PAR2) coronary arteries is markedly
      reduced in intramyocardial arteries when compared with epicardial arteries,
      suggesting increased regulation of PAR-mediated vascular responses in resistance
      type arteries.

PMID- 12055128
TI  - Blockade of neuropeptide Y(2) receptors and suppression of NPY's anti-epileptic
      actions in the rat hippocampal slice by BIIE0246.
AB  - Neuropeptide Y (NPY) has been shown to suppress synaptic excitation in rat
      hippocampus by a presynaptic action. The Y(2) (Y(2)R) and the Y(5) (Y(5)R)
      receptors have both been implicated in this action. We used the non-peptide,
      Y(2)R-selective antagonist, BIIE0246, to test the hypothesis that the Y(2)R
      mediates both the presynaptic inhibitory and anti-epileptic actions of NPY in rat
      hippocampus in vitro. NPY and the Y(2)R-selective agonist, [ahx(5-24)]NPY, both
      inhibited the population excitatory postsynaptic potential (pEPSP) evoked in area
      CA1 by stratum radiatum stimulation in a concentration-dependent manner. BIIE0246
      suppressed the inhibitory effects of both agonists, suppressing the maximal
      inhibition without causing a change in the agonist EC(50), in a manner
      inconsistent with competitive antagonism. BIIE0246 washed out from hippocampal
      slices extremely slowly. Application of agonist at high concentrations (1 - 3
      microM) for prolonged periods did not alter the rate of washout, but did
      partially overcome the antagonism, inconsistent with an insurmountable antagonism
      by BIIE0246. In the stimulus train-induced bursting (STIB) model of ictal
      activity in hippocampal slices, both NPY and [ahx(5-24)]NPY inhibited primary
      afterdischarge (1 degrees AD) activity. BIIE0246 (100 nM) completely suppressed
      the actions of NPY and [ahx(5-24)]NPY in this model. In contrast, the potent
      Y(5)R-selective agonist, Ala(31)Aib(32)NPY, affected neither 1 degrees AD
      activity in the presence of BIIE0246, nor, by itself, even the pEPSP in CA1.
      BIIE0246 potently suppresses NPY actions in rat hippocampus, suggesting a
      dominant role for Y(2)R there. The apparently insurmountable antagonism observed
      may result from the lipophilic nature of the antagonist.

PMID- 12055129
TI  - Differences in potency and efficacy of a series of
      phenylisopropylamine/phenylethylamine pairs at 5-HT(2A) and 5-HT(2C) receptors.
AB  - The pharmacological profile of a series of (+/-)-2,5-dimethoxy-4-(X)
      phenylisopropylamines (X=I, Br, NO(2), CH(3), or H) and corresponding
      phenylethylamines, was determined in Xenopus laevis oocytes injected with cRNA
      coding for rat 5-HT(2A) or 5-HT(2C) receptors. The efficacy and relative potency
      of these drugs were determined and compared to classical 5-HT(2) receptor
      agonists and antagonists. The rank order of agonist potency at the 5-HT(2A)
      receptor was: alpha-methyl-5-HT=5-HT>m-CPP>MK-212; at the 5-HT(2C) receptor the
      order was: 5-HT>alpha-methyl-5-HT>MK-212>m-CPP. All these compounds were full
      agonists at the 5-HT(2C) receptor, but alpha-methyl-5-HT and m-CPP showed lower
      efficacy at the 5-HT(2A) receptor. 4-(4-Fluorobenzoyl)-1-(4
      phenylbutyl)piperidine (4F 4PP) was 200 times more potent as a 5-HT(2A)
      antagonist than at 5-HT(2C) receptors. Conversely, RS 102221 was 100 times more
      potent as a 5-HT(2C) antagonist, confirming their relative receptor
      selectivities. The phenylisopropylamines were partial agonists at the 5-HT(2A)
      receptor, with I(max) relative to 5-HT in the 22+/-7 to 58+/-15% range; the
      corresponding phenylethylamines had lower or undetectable efficacies. All these
      drugs had higher efficacies at 5-HT(2C) receptors; DOI was a full 5-HT(2C)
      agonist. 2C-I and the other phenylethylamines examined showed relative efficacies
      at the 5-HT(2C) receptor ranging from 44+/-10% to 76+/-16%. 2C-N was a 5-HT(2)
      receptor antagonist; the mechanism was competitive at the 5-HT(2A), but non
      competitive at the 5-HT(2C) receptor. The antagonism was time-dependent at the 5
      HT(2C) receptor but independent of pre-incubation time at the 5-HT(2A) receptor
      subtype. The alpha-methyl group determines the efficacy of these
      phenylalkylamines at the 5-HT(2A) and 5-HT(2C) receptors.

PMID- 12055130
TI  - Extracellular ATP and UTP activate the protein kinase B/Akt cascade via the
      P2Y(2) purinoceptor in renal mesangial cells.
AB  - Extracellular nucleotides can activate a common purinoceptor mediating various
      cell responses. In this study we report that stimulation of rat mesangial cells
      with ATP and UTP leads to a rapid activation of the protein kinase B/Akt (PKB)
      pathway. Time-course studies reveal a rapid and transient phosphorylation of both
      Ser(473) and Thr(308) of PKB with a maximal effect after 5 min of stimulation.
      The response is concentration-dependent with a maximal effect at 30 microM of ATP
      and UTP. Western blot analysis of mesangial cells reveals the expression of the
      isoenzymes PKB-alpha and PKB-gamma, but not the PKB-beta. ATP and UTP also
      activate the upstream located PI 3-kinase-dependent kinase. Furthermore, the ATP-
      and UTP-induced PKB phosphorylation is abolished by two inhibitors of the PI 3
      kinase. In addition, suramin, a putative P2Y(2) receptor antagonist, and
      pertussis toxin, an inhibitor of G(i)/G(o) activation, markedly block ATP- and
      UTP-induced PKB phosphorylation. A series of ATP and UTP analogues were tested
      for their ability to stimulate PKB phosphorylation. UTP, ATP and gamma-thio-ATP
      are the only compounds capable of activating PKB. Stress-induced apoptosis of
      mesangial cells is reduced by the stable ATP analogue, gamma-thio-ATP, and this
      inhibitory effect is reversed in the presence of LY 294002. In summary, these
      results demonstrate that extracellular nucleotides are able to activate the PI 3
      kinase/PDK/PKB cascade via the P2Y(2)-receptor and a pertussis toxin-sensitive
      G(i) protein. Moreover, in mesangial cells this cascade may have an important
      role in the antiapoptotic response but not in the mitogenic or inflammatory
      response produced by extracellular nucleotides.

PMID- 12055131
TI  - Effects of the prostanoids on the proliferation or hypertrophy of cultured murine
      aortic smooth muscle cells.
AB  - Effects of the prostanoids on the growth of cultured aortic vascular smooth
      muscle cells (VSMCs) were examined using mice lacking prostanoid receptors.
      Proliferation of VSMCs was assessed by measuring [(3)H]-thymidine incorporation
      and the cell number, and their hypertrophy by [(14)C]-leucine incorporation and
      protein content. In VSMCs from wild-type mice, expressions of mRNAs for the EP(4)
      and TP were most abundant, followed by those for the IP, EP(3) and FP, when
      examined by competitive reverse transcriptase-PCR. Those for the EP(1), EP(2) and
      DP, however, could not be detected. AE1-329, an EP(4) agonist, and cicaprost, an
      IP agonist, inhibited platelet derived growth factor (PDGF)-induced proliferation
      of VSMCs from wild-type mice; these inhibitory effects disappeared completely in
      VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. In accordance with these
      effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type
      mice, which were absent in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively.
      Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar
      with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs
      from EP(4)(-/-) mice. PGD(2) inhibited PDGF-induced proliferation of VSMCs from
      both wild-type and DP(-/-) mice to a similar extent. This action of PGD(2) was
      also observed in VSMCs from EP4(-/-) and IP(-/-) mice. In VSMCs from wild-type
      mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP
      failed to show this action in VSMCs from TP(-/-) mice. The specific agonists for
      the EP(1), EP(2) or EP(3), and PGF(2)alpha showed little effect on the growth of
      VSMCs. These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced
      proliferation or hypertrophy of VSMCs via the EP(4), IP and TP, respectively, and
      that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not
      mediated by the DP, EP(4) or IP.

PMID- 12055132
TI  - Enhancement of delayed-rectifier potassium conductance by low concentrations of
      local anaesthetics in spinal sensory neurones.
AB  - Combining the patch-clamp recordings in slice preparation with the 'entire soma
      isolation' method we studied action of several local anaesthetics on delayed
      rectifier K(+) currents in spinal dorsal horn neurones. Bupivacaine, lidocaine
      and mepivacaine at low concentrations (1 - 100 microM) enhanced delayed-rectifier
      K(+) current in intact neurones within the spinal cord slice, while exhibiting a
      partial blocking effect at higher concentrations (>100 microM). In isolated
      somata 0.1 - 10 microM bupivacaine enhanced delayed-rectifier K(+) current by
      shifting its steady-state activation characteristic and the voltage-dependence of
      the activation time constant to more negative potentials by 10 - 20 mV. Detailed
      analysis has revealed that bupivacaine also increased the maximum delayed
      rectifier K(+) conductance by changing the open probability, rather than the
      unitary conductance, of the channel. It is concluded that local anaesthetics show
      a dual effect on delayed-rectifier K(+) currents by potentiating them at low
      concentrations and partially suppressing at high concentrations. The phenomenon
      observed demonstrated the complex action of local anaesthetics during spinal and
      epidural anaesthesia, which is not restricted to a suppression of Na(+)
      conductance only.

PMID- 12055133
TI  - Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to
      fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol.
AB  - Endocannabinoids are implicated in appetite and body weight regulation. In
      rodents, anandamide stimulates eating by actions at central CB1 receptors, and
      hypothalamic endocannabinoids may be under the negative control of leptin.
      However, changes to brain endocannabinoid levels in direct relation to feeding or
      changing nutritional status have not been investigated. We measured anandamide
      and 2-arachidonoyl glycerol (2-AG) levels in feeding-associated brain regions of
      rats, during fasting, feeding of a palatable food, or after satiation.
      Endocannabinoid levels were compared to those in rats fed ad libitum, at a point
      in their daily cycle when motivation to eat was absent. Fasting increased levels
      of anandamide and 2-AG in the limbic forebrain and, to a lesser extent, of 2-AG
      in the hypothalamus. By contrast, hypothalamic 2-AG declined as animals ate. No
      changes were detected in satiated rats. Endocannabinoid levels in the cerebellum,
      a control region not directly involved in the control of food intake, were
      unaffected by any manipulation. As 2-AG was most sensitive to variation during
      feeding, and to leptin regulation in a previous study, we examined the
      behavioural effects of 2-AG when injected into the nucleus accumbens shell, a
      limbic forebrain area strongly linked to eating motivation. 2-AG potently, and
      dose-dependently, stimulated feeding. This effect was attenuated by the CB1
      receptor antagonist SR141716. These findings provide the first direct evidence of
      altered brain levels of endocannabinoids, and of 2-AG in particular, during
      fasting and feeding. The nature of these effects supports a role for
      endocannabinoids in the control of appetitive motivation.

PMID- 12055134
TI  - YC-1 increases cyclo-oxygenase-2 expression through protein kinase G- and p44/42
      mitogen-activated protein kinase-dependent pathways in A549 cells.
AB  - YC-1, an activator of soluble guanylate cyclase (sGC), has been shown to increase
      the intracellular cGMP concentration. This study was designed to investigate the
      signaling pathway involved in the YC-1-induced COX-2 expression in A549 cells. YC
      1 caused a concentration- and time-dependent increase in COX activity and COX-2
      expression in A549 cells. Pretreatment of the cells with the sGC inhibitor (ODQ),
      the protein kinase G (PKG) inhibitor (KT-5823), and the PKC inhibitors (Go 6976
      and GF10923X), attenuated the YC-1-induced increase in COX activity and COX-2
      expression. Exposure of A549 cells to YC-1 caused an increase in PKC activity;
      this effect was inhibited by ODQ, KT-5823 or Go 6976. Western blot analyses
      showed that PKC-alpha, -iota, -lambda, -zeta and -mu isoforms were detected in
      A549 cells. Treatment of A549 cells with YC-1 or PMA caused a translocation of
      PKC-alpha, but not other isoforms, from the cytosol to the membrane fraction.
      Long-term (24 h) treatment of A549 cells with PMA down-regulated the PKC-alpha.
      The MEK inhibitor, PD 98059 (10 - 50 microM), concentration-dependently
      attenuated the YC-1-induced increases in COX activity and COX-2 expression.
      Treatment of A549 cells with YC-1 caused an activation of p44/42 MAPK; this
      effect was inhibited by KT-5823, Go 6976, long-term (24 h) PMA treatment or
      PD98059, but not the p38 MAPK inhibitor, SB 203580. These results indicate that
      in human pulmonary epithelial cells, YC-1 might activate PKG through an upstream
      sGC/cGMP pathway to elicit PKC-alpha activation, which in turn, initiates p44/42
      MAPK activation, and finally induces COX-2 expression.

PMID- 12055135
TI  - Multiple effects of trichloroethanol on calcium handling in rat submandibular
      acinar cells.
AB  - The effect of trichloroethanol (TCEt), the active metabolite of chloral hydrate,
      on the intracellular concentration of calcium ([Ca(2+)](i)) was investigated in
      rat submandibular glands (RSMG) acini loaded with fura-2. TCEt (1 - 10 mM)
      increased the [Ca(2+)](i) independently of the presence of calcium in the
      extracellular medium. Dichloroethanol (DCEt) and monochloroethanol (MCEt)
      reproduced the stimulatory effect of TCEt but at much higher concentrations
      (about 6 fold higher for DCEt and 20 fold higher for MCEt). TCEt mobilized an
      intracellular pool of calcium, which was depleted by a pretreatment with
      thapsigargin, an inhibitor of the sarcoplasmic and endoplasmic reticulum calcium
      dependent ATPases, but not with FCCP, an uncoupler of mitochondria. TCEt 10 mM
      inhibited by 50% the thapsigargin-sensitive microsomal Ca(2+)-ATPase. DCEt 10 mM
      and MCEt 10 mM inhibited the ATPase by 20 and 10%, respectively. TCEt inhibited
      the increase of the [Ca(2+)](i) and the production of inositol phosphates in
      response to carbachol, epinephrine and substance P. TCEt inhibited the uptake of
      calcium mediated by the store-operated calcium channel (SOCC). ATP and Bz-ATP
      increased the [Ca(2+)](i) in RSMG acini and this effect was blocked by
      extracellular magnesium, by Coomassie blue and by oxydized ATP (oATP). TCEt
      potentiated the increase of the [Ca(2+)](i) and of the uptake of extracellular
      calcium in response to ATP and Bz-ATP. TCEt had no effect on the uptake of barium
      and of ethidium bromide in response to purinergic agonists. These results suggest
      that TCEt, at sedative concentrations, exerts various effects on the calcium
      regulation: (1) it mobilizes a thapsigargin-sensitive intracellular pool of
      calcium in RSMG acini; (2) it inhibits the uptake of calcium via the SOCC; (3) it
      inhibits the activation by G protein-coupled receptors of a polyphosphoinositide
      specific phospholipase C. It does not interfere with the activation of the
      ionotropic P2X receptors. The use of chloral hydrate should be avoided in studies
      exploring the in vivo responses to sialagogues.

PMID- 12055136
TI  - Influence of the CB(1) receptor antagonist, AM 251, on the regional haemodynamic
      effects of WIN-55212-2 or HU 210 in conscious rats.
AB  - In conscious, freely-moving, male, Sprague-Dawley rats, the regional haemodynamic
      responses to the synthetic cannabinoids, WIN-55212-2 and HU 210, were compared.
      The possible involvement of cannabinoid, CB(1)-receptors, or beta(2)
      adrenoceptors in the responses to WIN-55212-2 and HU 210 were investigated using
      the CB(1)-receptor antagonist, AM 251, or the beta(2)-adrenoceptor antagonist,
      ICI 118551, respectively. Both WIN-55212-2 (150 microg kg(-1)) and HU 210 (100
      microg kg(-1)) had pressor, renal, and mesenteric vasoconstrictor and
      hindquarters vasodilator actions, although the effects of HU 210 were much more
      sustained than those of WIN-55212-2. Lower doses of the cannabinoids (WIN-55212
      2, 50 microg kg(-1), HU 210, 10 microg kg(-1)) had less consistent actions. All
      the significant cardiovascular effects of WIN-55212-2 and HU 210 were antagonized
      by pretreatment with AM 251 (3 mg kg(-1)). Furthermore, pretreatment with the
      beta(2)-adrenoceptor antagonist, ICI 118551, inhibited the hindquarters
      vasodilator effects of WIN-55212-2 and of HU 210. On the basis of the present
      findings, and our earlier work, it is suggested that, in conscious rats, the
      pressor and vasoconstrictor effects of HU 210 and WIN-55212-2 involve cannabinoid
      receptor-mediated increases in sympathetic activity. The accompanying
      hindquarters vasodilator actions of these agonists are cannabinoid receptor
      mediated and appear to involve beta(2)-adrenoceptors.

PMID- 12055137
TI  - Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced
      arthritis in rats.
AB  - The contribution of nitric oxide (NO) to articular pain in arthritis induced by
      zymosan (1 mg, intra articular) in rats was assessed by measuring articular
      incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS)
      inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors
      aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.)
      inhibited the AI induced by injection of zymosan 30 min later. Local (intra
      articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol;
      1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or
      local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1
      micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h
      after zymosan did not affect the subsequent AI. Local treatment with the NO
      donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p.
      inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L
      NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood
      pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema
      induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan
      arthritis only when given before the zymosan. This was not due to inhibition of
      articular PGE(2) release or oedema. NO donors also promoted antinociception in
      zymosan arthritis without affecting oedema.

PMID- 12055138
TI  - Pharmacologically activated migration of aortic endothelial cells is mediated
      through p38 SAPK.
AB  - Impairment in endothelial cell (EC) function plays a central role in vascular
      diseases (e.g. atherosclerosis, restenosis, diabetic angiopathies, microvascular
      angina, peripheral arterial disease). BRX-235 (a novel small molecule synthesized
      by Biorex, Hungary) has a potent vasculoprotective activity in different in vivo
      and in vitro studies. Since the importance of the p38 pathway in EC homeostasis
      and migration in particular is well documented, we have carried out studies to
      address the role of the p38 stress activated protein kinase (p38 SAPK) in the
      mode of action of BRX-235. In this study, Bovine aortic endothelial cells were
      used in a wounding migration assay (WMA) and for Western-blot analysis to study
      the effect and molecular mechanism of BRX-235-induced EC migration. The bovine
      aortic endothelial (BAE) cells were shown to be good models for EC migration.
      Both endothelial cell growth factor (ECGF)- and BRX-235-induced BAE cell
      migration were shown to be inhibited by SB 203580, a specific inhibitor of p38
      SAPK. It was also shown that, BRX-235 induces phosphorylation of p38 SAPK without
      affecting p38 SAPK protein levels. Thus, BRX-235 acts upstream of p38 SAPK. In
      summary, we have shown that p38 SAPK is a potential pharmacological mediator for
      candidate drugs that target the endothelium.

PMID- 12055139
TI  - Sirolimus/cyclosporine/tacrolimus interactions on bile flow and biliary excretion
      of immunosuppressants in a subchronic bile fistula rat model.
AB  - The new immunosuppressive agent sirolimus generally is combined in transplant
      patients with cyclosporine and tacrolimus which both exhibit cholestatic effects.
      Nothing is known about possible cholestatic effects of these combinations which
      might be important for biliary excretion of endogenous compounds as well as of
      immunosuppressants. Rats were daily treated with sirolimus (1 mg kg(-1) p.o.),
      cyclosporine (10 mg kg(-1) i.p.), tacrolimus (1 mg kg(-1) i.p.), or a combination
      of sirolimus with cyclosporine or tacrolimus. After 14 days a bile fistula was
      installed to investigate the effects of the immunosuppressants and their
      combinations on bile flow and on biliary excretion of bile salts, cholesterol,
      and immunosuppressants. Cyclosporine as well as tacrolimus reduced bile flow (
      22%; -18%), biliary excretion of bile salts (-15%;-36%) and cholesterol (-15%; 
      47%). Sirolimus decreased bile flow by 10%, but had no effect on cholesterol or
      bile salt excretion. Combination of sirolimus/cyclosporine decreased bile flow
      and biliary bile salt excretion to the same extent as cyclosporine alone, but led
      to a 2 fold increase of biliary cholesterol excretion. Combination of
      sirolimus/tacrolimus reduced bile flow only by 7.5% and did not change biliary
      bile salt and cholesterol excretion. Sirolimus enhanced blood concentrations of
      cyclosporine (+40%) and tacrolimus (+57%). Sirolimus blood concentration was
      increased by cyclosporine (+400%), but was not affected by tacrolimus. We
      conclude that a combination of sirolimus/tacrolimus could be the better
      alternative to the cotreatment of sirolimus/cyclosporine in cholestatic patients
      and in those facing difficulties in reaching therapeutic ranges of sirolimus
      blood concentration.

PMID- 12055141
TI  - Effect of dopamine receptor agonists on sensory nerve activity: possible
      therapeutic targets for the treatment of asthma and COPD.
AB  - Sensory nerves regulate central and local reflexes such as airway plasma leakage,
      and cough and their function may be enhanced during inflammation. Evidence
      suggests that dopamine receptor agonists may inhibit sensory nerve-mediated
      responses. In this study dopamine inhibited vagal sensory nerve induced
      microvascular leakage in the rat. In order to characterize the receptor involved
      rat vagus preparations were utilized. Quinagolide (D(2/3) agonist), ropinirole
      (D(2/3/4) agonist), SKF 38393 (D(1/5) agonist), AR-C68397AA (Viozan) (dual
      D(2)/B(2) agonist) and dopamine inhibited hypertonic saline induced
      depolarization by approximately 50%. Data suggests that AR-C68397AA and
      quinagolide also inhibited depolarization of the human vagus. The quinagolide
      response was blocked by sulpiride (D(2/3) antagonist) but not SCH 23390 (D(1/5)
      antagonist); ropinirole was partially blocked by sulpiride, totally blocked by
      spiperone (at a concentration that blocks all dopamine receptors) but not by SCH
      23390. The response to SKF 38393 was not blocked by sulpiride but was by SCH
      23390. The inhibition evoked by AR-C68397AA was only partially blocked by SCH
      23390 but not by sulpiride or spiperone whereas dopamine was blocked by
      spiperone. The effect of dopamine was not stimulus-specific as it inhibited
      capsaicin-induced depolarization of the rat vagus in a spiperone sensitive
      manner. In conclusion, dopamine receptor ligands inhibit depolarization of the
      rat and human vagus. These data suggest that dopamine receptor agonists may be of
      therapeutic benefit in the treatment of symptoms such as cough and mucus
      secretion which are evident in respiratory diseases such as asthma and chronic
      obstructive pulmonary disease.

PMID- 12055144
TI  - The accidental epidemiologist: losing the way or following social-epidemiological
      leads?

PMID- 12055142
TI  - Inhibition of glycine receptor function of native neurons by aliphatic n
      alcohols.
AB  - The inhibitory effects of n-alcohols (methanol to dodecanol) on glycine-activated
      currents were studied in neurons freshly dissociated from the ventral tegmental
      area of neonatal rats using whole-cell patch-clamp recording technique. Ethanol
      enhanced and depressed glycine-activated currents in 35% and 45%, respectively,
      of neurons of ventral tegmental area of neonatal rats. In this report, we
      extended our focus of ethanol-induced inhibition of glycine currents to other
      straight-chain alcohols. Aliphatic n-alcohols, which have carbon numbers less
      than nine, suppressed glycine currents in 45% (71/158) of the neurons. All
      results from this study are obtained from the 45% of cells displaying inhibition;
      the other 55% of the neurons were not studied. Alcohol potency increased as the
      number of carbon atoms increased from one to five, and was at a maximal plateau
      from five to nine; alcohols with 10 or more carbons did not inhibit glycine
      activated currents. Thus, a 'cutoff' point in their potency for inhibition of
      glycine receptor function occurred at about decanol. A coapplication of dodecanol
      with ethanol eliminated the inhibition resulting from ethanol. Thus, dodecanol
      may bind to the receptor silently and compete with ethanol. These observations
      indicate that straight-chain n-alcohols exhibit a 'cutoff' point in their potency
      for inhibition of the glycine receptor function between nine and 10 carbon atoms.
      The inability of longer alcohols to change the activation properties of the
      receptors may contribute to the cutoff effect.

PMID- 12055140
TI  - Docosahexaenoic acid potentiates interleukin-1beta induction of nitric oxide
      synthase through mechanism involving p44/42 MAPK activation in rat vascular
      smooth muscle cells.
AB  - The effect of docosahexaenoic acid (DHA) on nitric oxide (NO) production and
      inducible NO synthase (iNOS) expression induced by interleukin (IL)-1beta, and
      whether the effect of DHA is related to its effect on mitogen-activated protein
      kinase (MAPK) activation were investigated in cultured rat vascular smooth muscle
      cells (VSMCs). DHA and eicosapentaenoic acid (EPA), although less potent,
      increased the NO production induced by IL-1beta (3 ng ml(-1)) in a concentration
      dependent manner (3 - 30 microM) Arachidonic acid had no significant effect. The
      stimulatory effect of DHA (30 microM) on the NO production was more obvious at
      lower concentrations of IL-1beta. IL-1beta induced iNOS protein and mRNA
      expressions, which were significantly potentiated by DHA. EPA (30 microM) had a
      tendency to increase the iNOS protein and mRNA expressions, but arachidonic acid
      had no effect. IL-1beta-induced iNOS protein expression was significantly
      inhibited by PD 98059 (10 microM), a selective inhibitor of p44/42 MAPK kinase,
      both in the absence and the presence of DHA. SB 203580 (10 microM), a selective
      inhibitor of p38 MAPK activity, had no significant effect, although had a
      tendency to inhibit slightly. IL-1beta increased the phosphorylation of p44/42
      MAPK, while it did not apparently increase the phosphorylation of p38 MAPK. DHA
      significantly potentiated the IL-1beta-induced phosphorylation of p44/42 MAPK,
      while it had no significant effect on the phosphorylation of p38 MAPK. These
      results suggest that DHA increases NO production by potentiating iNOS expression
      induced by IL-1beta through mechanism involving p44/42 MAPK signalling cascade in
      rat VSMCs. The present study may contribute to the understanding of basic
      mechanisms underlying the beneficial effects of DHA on various cardiovascular
      disorders.

PMID- 12055145
TI  - Road safety in less-motorized environments: future concerns.
AB  - In the last three decades, the incidence of traffic crash fatalities and injuries
      has been reduced significantly in the high-income countries but not in the low-
      and middle-income countries. The traffic patterns in the former are not only
      different but are also less complex than those in the latter. Traffic in low
      income countries comprises a much higher share of vulnerable road users and so
      vehicles, roads and the environment have to be designed for their safety.
      Solutions for such problems are not readily available and very innovative work
      needs to be done around the world to arrive at new policies and designs. In
      addition to crashworthiness of vehicles, transportation planning, exposure
      control, intelligent separation of non-motorized traffic on major roads, and
      traffic calming are likely to play a much more important role.

PMID- 12055146
TI  - Income and inequality as determinants of mortality: an international cross
      section analysis. 1979.

PMID- 12055147
TI  - Commentary: Liberty, fraternity, equality.

PMID- 12055149
TI  - Commentary: The convoluted story of international studies of inequality and
      health.

PMID- 12055148
TI  - Commentary: Theory in the fabric of evidence on the health effects of
      inequalities in income distribution.

PMID- 12055150
TI  - Commentary: Income inequality and health: the end of the story?

PMID- 12055151
TI  - Too much too young? Teenage pregnancy is not a public health problem.

PMID- 12055152
TI  - Too much too young? Teenage pregnancy is a public health, not a clinical,
      problem.

PMID- 12055153
TI  - Teen pregnancy is not a public health crisis in the United States. It is time we
      made it one.

PMID- 12055154
TI  - Too much too young? In Nepal more a case of too little, too young.

PMID- 12055155
TI  - What a difference a year makes? Too little too late.

PMID- 12055156
TI  - Domestic violence across generations: findings from northern India.
AB  - BACKGROUND: Although one cannot underestimate the importance of macrosystem-level
      forces (such as cultural and social norms) in the aetiology of gender-based
      violence within any country, including India, individual-level variables (such as
      observing violence between one's parents while growing up) may also play
      important roles in the development of such violence. Therefore, this research
      studies men residing in northern India to: (1) estimate the prevalence of men's
      childhood experiences of witnessing parent-to-parent violence within their
      families of origin; (2) examine whether men raised in violent homes were more
      likely than men raised in non-violent homes to have attitudes supportive of
      husbands' control of their wives; (3) examine whether men raised in violent homes
      were more likely than men raised in non-violent homes to be abusive toward their
      own wives; and (4) estimate the extent to which wife abuse in this second
      generation could have been prevented had there not been parent-to-parent violence
      in the men's natal families. METHODS: Married men (n = 6902) were surveyed
      concerning: their childhood experiences of witnessing parent-to-parent violence
      in their families of origin; their attitudes regarding the appropriateness of
      husbands' control of their wives; their physically and sexually abusive
      behaviours toward their own wives; and sociodemographic variables. Descriptive
      statistics, multivariable modelling procedures, and estimation of a population
      attributable fraction were used to address the study questions. RESULTS:
      Approximately one-third of the men had witnessed parent-to-parent violence as a
      child. Compared to men raised in non-violent homes, men from violent homes were
      significantly more likely to believe in husbands' rights to control their wives,
      and to be physically/sexually abusive toward their own wives. Non-violence in the
      earlier generation was strongly predictive of non-violence in the second
      generation, with about a third of the wife abuse in the second generation being
      attributable to parent-to-parent violence in the first generation. CONCLUSIONS:
      These findings from northern India are congruent with those from other
      geographical/cultural settings in suggesting that witnessing violence between
      one's parents while growing up is an important risk factor for the perpetration
      of partner violence in adulthood.

PMID- 12055157
TI  - Mortality, severe morbidity and injury among long-term lone mothers in Sweden.
AB  - BACKGROUND: Being a lone mother often implies disadvantage in terms of both
      socioeconomic circumstances and health. Our aim was to examine differences in
      mortality, severe morbidity and injury between lone mothers and mothers living
      with partners, on the assumption that the disadvantaged socioeconomic
      circumstances contribute to poor health. METHODS: The odds for receipt of
      hospital care or death between 1991 and 1994 were estimated for 26 619 lone
      mothers and 379 855 partnered mothers from data collected for the Swedish
      Population and Housing Census of 1990. We computed odds ratios by means of
      logistic regression, adjusting for confounders, mediators, and factors with an
      indeterminate position in various models. To control for health-selection
      effects, we only considered initially healthy women, as measured by non
      hospitalization 4 years prior to follow-up. To reduce the impact of distress
      following divorce on health, we only included mothers who had been either lone or
      partnered for a period of > or =5 years. RESULTS: Lone mothers showed increased
      risks of total mortality, lung cancer, suicide/ suicide attempt, inflicted
      violence, traffic injury and other accident, psychiatric disease, and addiction.
      The main explanation for increased risks seems for most outcomes to lie in
      deficient household resources, as indicated here by receipt of social-welfare
      benefit and housing situation. For all the initially elevated outcomes, except
      for total mortality, significant risk increases remained unaccounted for even in
      the full model. Relationships varied according to subgroup. Lone motherhood was
      not related to accident, suicide and addiction among medium- and high-grade non
      manual workers. Although lone mothers in general showed no increased risk of
      ischaemic heart disease, those receiving social benefit were exposed to a
      significantly increased risk. CONCLUSIONS: Our findings suggest that lone
      motherhood entails health disadvantages. Lack of household resources seems to
      play a major role in accounting for increased risks, but the risks are partly
      independent of socioeconomic circumstances, selection factors, and distress
      following divorce.

PMID- 12055158
TI  - Vulnerability to homicide in Karachi: political activity as a risk factor.
AB  - BACKGROUND: Previous studies analysing Karachi ambulance data from 1993 to 1995
      identified neighbourhoods in Karachi disproportionately affected by homicide. As
      a step toward developing intervention programmes to curb violence, we conducted a
      study to identify risk factors for becoming a homicide victim in a high violence
      area of Karachi. METHODS: We interviewed families of 35 cases, individuals
      intentionally killed through acts of violence between January 1994 and January
      1997, and 85 community-based controls frequency matched by sex, from Orangi, a
      high violence area of Karachi. RESULTS: Most of our cases and controls were male
      (97% and 92%, respectively) and had similar socioeconomic and ethnic backgrounds.
      All the victims were killed by firearms; 4 (11%) had been tortured prior to
      death. Most of the victims were killed in the streets (n = 25, 71%). Of these, 7
      (36%) had been killed by law-enforcement officers, while 6 (24%) died from
      indiscriminate firing. People who were killed were 34 times more likely to have
      attended all political processions (29% versus 1%, odds ratio [OR] = 34; 95% CI:
      4-749, P < 0.001), 19 times more likely to have attended political meetings (31%
      versus 2%, OR = 19; 95% CI: 4-136, P < 0.001), and 17 times more likely to have
      held an important position in a political party (29% versus 2%, OR = 17; 95% CI:
      3-120, P < 0.001) than controls. CONCLUSIONS: Homicide in Orangi was political.
      Efforts to improve trust between ethnic groups and to build legitimacy for non
      violent forms of conflict resolution are important steps to limit future
      violence.

PMID- 12055159
TI  - Commentary: Studying political violence: we should push for more from
      epidemiology.

PMID- 12055160
TI  - An ecologic study of protective equipment and injury in two contact sports.
AB  - BACKGROUND: Contact sports have high rates of injury. Protective equipment
      regulations are widely used as an intervention to reduce injury risk. The purpose
      of this study was to investigate the injury prevention effect of regulations
      governing protective equipment in two full-body contact sports. METHODS: Injury
      rates in US collegiate football were compared to New Zealand club Rugby Union.
      Both sports involve significant body contact and have a high incidence of injury.
      Extensive body padding and hard-shell helmets are mandated in collegiate football
      but prohibited in Rugby Union. RESULTS: The injury rate in football was
      approximately one-third the rugby rate (rate ratio [RR] = 0.35; 95% CI: 0.31
      0.40). The head was the body site with the greatest differential in injury
      incidence (RR = 0.11; 95% CI: 0.08-0.16). Rugby players suffered numerous
      lacerations, abrasions, and contusions to the head region, but the incidence of
      these injuries in football was almost zero (RR = 0.01; 95% CI: 0.01-0.03). Injury
      rates were more similar for the knee (RR = 0.61; 95% CI: 0.43-0.87) and ankle (RR
      = 0.72; 95% CI: 0.46-1.13), two joints largely unprotected in both sports.
      CONCLUSIONS: The observed differences are consistent with the hypothesis that
      regulations mandating protective equipment reduce the incidence of injury,
      although important potential biases in exposure assessment cannot be excluded.
      Further research is needed into head protection for rugby players.

PMID- 12055161
TI  - Injury inequalities: morbidity and mortality of 0-17 year olds in Israel.
AB  - BACKGROUND: To determine whether there are inequalities in the incidence of fatal
      and non-fatal unintentional injuries among Jewish and Arab children in Israel.
      METHODS: A nationwide random sample of injured children aged 0-17 attending
      emergency rooms (ER) during one year was selected (n = 11 058). The number of
      cases was weighted to 365 days and rates and odds ratios (OR) were calculated.
      Logistic regression was performed to study the OR of hospitalization in the total
      population and among Jews and Arabs controlling for independent variables.
      RESULTS: The incidence of ER admissions among the Jews was 752.6/10 000 (95% CI:
      738.1-767.1), 1.5 times higher than among the Arabs (492.8/10 000, 95% CI: 472.8
      512.8). However, the rate of hospitalization was 1.1 times higher among Arabs
      than among Jews and the mortality rate was 3.2 times higher among Arabs than
      among Jews. CONCLUSIONS: The differences in injury rates for fatal and non-fatal
      injuries may be due to differences in the severity of injuries or in the use of
      services by the two populations. A study is underway to elucidate this point.

PMID- 12055162
TI  - Increasing inequalities in all-cause and cardiovascular mortality among US adults
      aged 25-64 years by area socioeconomic status, 1969-1998.
AB  - BACKGROUND: This study examined the extent to which areal socio-economic
      gradients in all-cause and cardiovascular disease (CVD) mortality among US men
      and women aged 25-64 years increased between 1969 and 1998. METHODS: Using factor
      analysis 17 census tract variables were used to develop an areal index of socio
      economic status that was used to stratify all US counties into five socio
      economic categories. By linking the index to county-level mortality data from
      1969 to 1998, we calculated annual age-adjusted mortality rates for each area
      socio-economic group. Poisson regression models were fitted to estimate areal
      socio-economic gradients in mortality over time. RESULTS: Areal socio-economic
      gradients in all-cause and cardiovascular mortality have increased substantially
      over the past three decades. Compared to men in the highest area socio-economic
      group, rates of all-cause and CVD mortality among men in the lowest area socio
      economic group were 42% and 30% greater in 1969-1970 and 73% and 79% greater in
      1997-1998, respectively. The gradients in mortality among women were steeper for
      CVD than for all causes. Compared to women in the highest area socio-economic
      group, rates of all-cause and CVD mortality among women in the lowest area socio
      economic group were 29% and 49% greater in 1969-1970 and 53% and 94% greater in
      1997-1998, respectively. CONCLUSIONS: Although US all-cause and cardiovascular
      mortality declined for all area socio-economic groups during 1969-1998, the
      gradient increased because of significantly larger mortality declines in the
      higher socio-economic groups. Increasing areal inequalities in mortality shown
      here may be related to increasing temporal differences in the material and social
      living conditions between areas.

PMID- 12055163
TI  - Socioeconomic inequalities in cardiovascular mortality and the role of work: a
      register study of Finnish men.
AB  - BACKGROUND: In Finland, socioeconomic inequalities in mortality have been well
      documented. However, the role of working conditions in the emergence of those
      inequalities has not been thoroughly examined. METHODS: Data came from the
      Longitudinal Census file, which included censuses since 1970 (every 5 years). The
      cohort consisted of men who were in the same occupation in 1975 and 1980, and who
      were between 25 and 64 years old in 1980. Farm work, mining and military
      occupations were excluded. Cardiovascular mortality of this cohort was followed
      up 1981-1994 (5.4 million person-years). Information on marital status, education
      and income was updated in 1985 and 1990. Working conditions were evaluated at
      occupational level (job exposure matrix). Poisson regression analyses were
      conducted to estimate the impact of independent variables on mortality.
      Inequalities were assessed in relation to occupational class and occupational
      category. RESULTS: According to the models, elimination of unfavourable working
      conditions would have reduced the number of all cardiovascular deaths by 8%,
      myocardial infarctions by 10%, and cerebrovascular deaths by 18%. The most
      influential job exposures appeared to be high workload, low control, noise, and
      shift work. Income had a strong effect on mortality. CONCLUSIONS: Working
      conditions explained a relatively small portion of socioeconomic inequalities in
      mortality. Inequalities associated with occupational category and class were more
      attributable to varying levels of education and income.

PMID- 12055164
TI  - Commentary: Cheap but cheerless. Is it the underpaid or the overworked who die
      young?

PMID- 12055165
TI  - Relation of adult lifestyle and socioeconomic factors to the prevalence of
      Helicobacter pylori infection.
AB  - INTRODUCTION: The influence of adult socioeconomic status, co-habitation, gender,
      smoking, coffee and alcohol intake on risk of Helicobacter pylori infection is
      uncertain. METHODS: Subjects between aged 40-49 years were randomly invited to
      attend their local primary care centre. Participants were interviewed by a
      researcher on smoking, coffee and alcohol intake, history of living with a
      partner, present and childhood socioeconomic conditions. Helicobacter pylori
      status was determined by 13C-urea breath test. RESULTS: In all, 32 929 subjects
      were invited, 8429 (26%) were eligible and 2327 (27.6%) were H. pylori positive.
      Helicobacter pylori infection was more common in men and this association
      remained after controlling for childhood and adult risk factors in a logistic
      regression model (odds ratio [OR] = 1.15; 95% CI: 1.03-1.29). Living with a
      partner was also an independent risk factor for infection (OR = 1.30; 95% CI:
      1.01-1.67), particularly in partners of lower social class (social class IV and V
      OR = 1.47; 95% CI: 1.19-1.81, compared with social class I and II). Helicobacter
      pylori infection was more common in lower social class groups (I and II-22%
      infected, III-29% infected, IV and V-38% infected) and there was a significant
      increase in risk of infection in manual workers compared with non-manual workers
      after controlling for other risk factors (OR = 1.18; 95% CI: 1.03-1.34). Alcohol
      and coffee intake were not independent risk factors for infection and smoking was
      only a risk factor in those smoking >35 cigarettes a day. CONCLUSIONS: Male
      gender, living with a partner and poor adult socioeconomic conditions are
      associated with increased risk of H. pylori infection.

PMID- 12055166
TI  - History of breastfeeding and Helicobacter pylori infection in pre-school
      children: results of a population-based study from Germany.
AB  - BACKGROUND: Helicobacter pylori infection is predominantly acquired in early
      childhood. Therefore, childhood nutrition may be related to acquisition of
      infection. However, there are few current data from developed countries to
      elucidate this association. We investigated the relation between history of
      breastfeeding and H. pylori infection in a large population-based sample.
      METHODS: Study subjects were all pre-school children in the city of Ulm, located
      in southern Germany and two nearby communities who were screened for school
      fitness between January and July 1997. The infection status of the children and
      of the accompanying mother was determined by the 13C-urea breath test. The
      parents provided additional information through a standardized questionnaire.
      RESULTS: In all, 946 children (mean age 5.9 years) and their mothers were
      included in the final analysis (response in study population 80.2%). Overall, H.
      pylori prevalence was 9.8% in children and 34.7% in their mothers; there was a
      strong association between children's and mother's infection. Of the children,
      82.5% had ever been breastfed. Prevalence of H. pylori infection was higher in
      children breastfed compared to never breastfed children (10.1% versus 8.4%) and
      showed a positive relationship with duration of breastfeeding. After controlling
      for covariates, including mother's H. pylori status, by means of multivariable
      analysis, the odds ratio (OR) for children's H. pylori infection was 1.56 (95%
      CI: 0.79-3.11) for any versus never breastfeeding and 2.57 (95% CI: 1.19-5.55)
      given the child was breastfed > or =6 months. CONCLUSIONS: These data suggest
      that breastfeeding in infancy does not protect against H. pylori infection among
      pre-school children in industrialized countries.

PMID- 12055167
TI  - Helicobacter pylori infection in rural China: demographic, lifestyle and
      environmental factors.
AB  - BACKGROUND: Although Helicobacter pylori is one of the most common human
      bacterial infections worldwide, its mode of transmission is unclear. METHODS: To
      investigate possible associations between H. pylori infection and demographic,
      lifestyle, and environmental factors in a rural Chinese population, a cross
      sectional survey was administered to 3288 adults (1994 seropositive, 1019
      seronegative, 275 indeterminate) from 13 villages in Linqu County, Shandong
      Province, China. RESULTS: Helicobacter pylori prevalence was elevated for:
      infrequent handwashing before meals (OR = 1.7, 95% CI: 1.0-3.0), crowding (i.e.
      sharing a bed with >2 people [OR = 2.3, 95% CI: 1.3-4.2]), washing/bathing in a
      pond or ditch (OR = 1.5, 95% CI: 1.0-2.4), and medium (OR = 1.6, 95% CI: 1.3-2.0)
      and low (OR = 2.3, 95% CI: 1.9-2.9) compared to high village education level, and
      reduced for never being married or divorced (OR = 0.4, 95% CI: 0.2-1.0). There
      was also a suggestion that source of drinking water, especially water from a
      shallow village well might be related to H. pylori seropositivity. There was no
      evidence of an association between H. pylori prevalence and alcohol or tobacco
      use, raw fruit and vegetable intake, or individual social class measures.
      CONCLUSIONS: The results of this study suggest that person-to-person transmission
      is the most plausible route of H. pylori infection in this rural Chinese
      population, but waterborne exposures deserve further investigation.

PMID- 12055168
TI  - Commentary: What remains to be done regarding transmission of Helicobacter
      pylori.

PMID- 12055169
TI  - Neonatal tetanus: mortality rate and risk factors in Loralai District, Pakistan.
AB  - BACKGROUND: This study was conducted to estimate the neonatal tetanus (NNT)
      mortality rate and to identify the risk factors for NNT deaths in Loralai
      District, Pakistan. METHOD: We conducted a community-based cross-sectional survey
      during July-September 1997. We stratified the sample proportionate to population
      of union councils. The most populous village in a union council was selected
      first. We interviewed the women, selected randomly, who had a live birth in the
      18 months preceding the survey. We conducted a matched case-control study to
      identify the risk factors for NNT deaths. We used the World Health Organization
      criteria to enrol cases, identified during the cross-sectional survey or
      registered at the district hospital. We enrolled three community-based controls
      per case, matched on the area of residence, immunization status and date of
      birth. RESULTS: Of the 1547 live births, there were 36 neonatal deaths due to
      tetanus. The NNT mortality rate in the district was 23 per 1000 live births (95%
      CI: 16-30). For the case-control study, we enrolled 41 cases and 123 controls.
      Using conditional logistic regression, the risk of NNT death was increased with
      the use of soil as delivery surface (O.R = 3.2, 95% CI: 1.1-10.2), father's
      illiteracy (OR = 3.2, 95% CI: 1.3-8.1) and possession of sheep at home (OR = 2,
      95% CI: 1.0-5.0). The population attributable risk per cent for soil as delivery
      surface was 64%. CONCLUSION: Transmission of infection while using soil as the
      delivery surface can occur through direct or indirect contamination of the fresh
      umbilical wound. Use of safer delivery practices in general and clean surfaces in
      particular should be encouraged to reduce the NNT mortality rate in the area.

PMID- 12055170
TI  - The heavier the better? Birthweight and perinatal mortality in different ethnic
      groups.
AB  - BACKGROUND: Mother's ethnicity is associated with her baby's birthweight and risk
      of perinatal mortality. Given the close relation between birthweight and
      perinatal mortality, we explored whether ethnic differences in birthweight
      explain ethnic differences in perinatal mortality. METHODS: Data on all births to
      mothers born in Norway (808 658), Pakistan (6854), Vietnam (3283) and North
      Africa (1461) from 1980 to 1995 were obtained from the Medical Birth Registry of
      Norway. The associations between birthweight and perinatal mortality among ethnic
      groups were analysed using univariate and multivariate methods. RESULTS: Mean
      birthweights were low for Vietnamese and Pakistani mothers (3202 g, 3244 g) and
      high for Norwegian and North African mothers (3530 g, 3559 g). Mean birthweights
      were largely unrelated to perinatal mortality, which was lowest for Vietnamese
      (8.2/1000, 95% CI: 5.1-11.3) and highest for Pakistanis (14.9/1000, 95% CI: 12.0
      17.7). Intermediate perinatal mortality rates were found among Norwegians
      (9.5/1000, 95% CI: 9.3-9.7) and North Africans (9.6/1000, 95% CI: 4.6-14.6).
      Further comparison of weight-specific mortality rates between the two largest
      ethnic groups showed the low birthweight paradox, where among low-weight births,
      perinatal mortality was lower among Pakistani than among Norwegian babies.
      However, adjustment to a relative birthweight scale (units of standard deviations
      from population-specific mean value) revealed higher rates of weight-specific
      mortality among Pakistanis across the entire range of birthweights. Multivariate
      adjustment for relative birthweight and other factors did not change these
      results. CONCLUSIONS: Differences in perinatal mortality between the ethnic
      groups were not explained by differences in mean birthweight. Paradoxical
      differences in birthweight-specific mortality rates could be resolved by
      adjustment to a relative scale.

PMID- 12055171
TI  - Can clinical risk factors for late stillbirth in West Africa be detected during
      antenatal care or only during labour?
AB  - BACKGROUND: Recent studies have shown that the most important risk factors for
      perinatal mortality in developing countries are not detectable during antenatal
      care but can be observed only shortly before or during labour. Although 60% of
      perinatal deaths in these countries are stillbirths, few epidemiological studies
      focus on them. We tested the hypothesis that the risk factors for late stillbirth
      in West Africa are detectable principally shortly before or during labour.
      METHODS: Data came from a prospective population-based study (the MOMA survey)
      that collected information about 20 326 pregnant women in seven areas, primarily
      urban, in West Africa. RESULTS: There were 19 870 singleton births. The
      stillbirth rate was 25.9 per 1000 total births (95% CI: 23.7-28.1). In the crude
      analysis, after adjustment and consideration of prevalence, the principal risk
      factors for late stillbirth were: late antenatal or intrapartum vaginal bleeding,
      intrapartum hypertension, dystocia, and infection. Other risk factors were:
      maternal height (<150 cm), maternal age (>35 years), previous stillbirths,
      hypertension at the 8-month antenatal visit and number of antenatal visits (<2).
      CONCLUSIONS: The principal risk factors for late stillbirth observed in our study
      could be detected only in the late antenatal and intrapartum period. These
      results highlight the potential benefits of partograph use. They need to be
      confirmed by studies incorporating continuous intrapartum fetal monitoring.

PMID- 12055172
TI  - Relative risk for genetic associations: the case-parent triad as a variant of
      case-cohort design.
AB  - The contribution of this paper is to conceptualize the case-parent triad within
      an epidemiological framework. We propose that the case-parent triad design is a
      variant of the case-cohort design. The affected offspring of case-parent triads
      come from a source cohort of all offspring of parents in a population. We first
      demonstrate that if the source cohort is restricted to offspring of a certain
      parental mating type then the relative risk in relation to genetic exposure can
      be estimated simply from the ratio of the number of exposed to the number of
      unexposed affected offspring. We then extend the logic to studies including
      offspring of all parental mating types; provided that the allele frequencies and
      possible parental mating types are specified, a valid relative risk can still be
      estimated. Compared to prior descriptions of the case-parent triad design, the
      proposed approach is readily understandable, epidemiologically meaningful and
      provides a relatively simple perspective for estimating valid measure of effect.
      Also, by allowing the potential sources of selection bias to be revealed more
      easily the design is made more accessible both conceptually and practically to
      epidemiologists.

PMID- 12055174
TI  - Mind the gap--hierarchies, health and human evolution.

PMID- 12055173
TI  - Estimating the number of Cubans infected sexually by human immunodeficiency virus
      using contact tracing data.
AB  - BACKGROUND: To estimate the yearly number of people in Cuba who are living with
      human immunodeficiency virus (HIV) and were infected through sexual contact but
      who have not developed acquired immunodeficiency syndrome (AIDS). Estimation was
      made directly from the yearly HIV seroprevalence data of the Cuban Partner
      Notification Programme from 1991 to 2000. METHODS: The generalized removal model
      for open populations is utilized for the estimation. The total number of known
      HIV-infected Cubans at each sampling time is used in the prior to provide more
      reasonable approximations. RESULTS: We estimated a yearly survival rate of 93%.
      The median estimates for the number of all living asymptomatic HIV-positive
      Cubans, infected by sexual contact, tripled from 714 in 1991 to 2170 in 2000. The
      number of unknown HIV-positive Cubans infected sexually is estimated to range
      from 174 in 1991 to 401 in 2000. CONCLUSIONS: A consistent increase in the number
      of sexually infected HIV-positive individuals in Cuba from 1991 to 2000 is
      evident from the estimates. From 1996 onwards more sexually active
      homosexual/bisexual contacts were traced and consequently more sexually-infected
      HIV-positives were detected. A consequence of increased detection is the
      levelling off and subsequent decrease in the number of unknown HIV-positives
      during this time period. The estimation procedure is useful in estimating
      prevalent population sizes of epidemiological and public health interest.

PMID- 12055175
TI  - Exploring the relationships between income inequality, socioeconomic status and
      health: a self-guided tour?

PMID- 12055176
TI  - Chagas' disease among older adults: branches or mainstream of the present burden
      of Trypanosoma cruzi infection?

PMID- 12055177
TI  - Jerry Morris and health services research in the USA.

PMID- 12055180
TI  - Identification, tissue expression, and functional characterization of Otx3, a
      novel member of the Otx family.
AB  - Transcription factors containing a homeodomain play an important role in the
      organogenesis of vertebrates. We have isolated a novel homeodomain transcription
      factor, Otx3, which is structurally and functionally related to Otx1 and Otx2,
      transcription factors that are critical in brain morphogenesis. Mouse Otx3 is a
      protein composed of 376 amino acids. Otx3 mRNA was expressed in mouse embryos
      from 10.5 to 13.5 days postcoitum (dpc) and in adult cerebellum as assessed by
      Northern blotting. Whole-mount in situ hybridization of mouse embryos from 9.5 to
      11.5 dpc revealed strong expression of Otx3 mRNA in the diencephalon,
      mesencephalon, metencephalon, myelencephalon, and developing eye, indicating an
      expression pattern largely overlapping but distinct from those of Otx1 and Otx2.
      In addition, Otx3 was shown by electrophoretic mobility shift assay to bind to
      the TAATCC motif, the consensus binding sequence for Otx1, Otx2, and Crx. Results
      of a transcription reporter assay suggest that Otx3 functions as a transcription
      repressor by binding to this motif. These results suggest that Otx3 is a novel
      member of the Otx family and may be involved in the development of the central
      nervous system.

PMID- 12055181
TI  - Inositol 3,4,5,6-tetrakisphosphate inhibits insulin granule acidification and
      fusogenic potential.
AB  - ClC Cl(-) channels in endosomes, synaptosomes, lysosomes, and beta-cell insulin
      granules provide charge neutralization support for the functionally indispensable
      acidification of the luminal interior by electrogenic H(+)-ATPases (Jentsch, T.
      J., Stein, V., Weinreich, F., and Zdebik, A. A. (2002) Physiol. Rev. 82, 503
      568). Regulation of ClC activity is, therefore, of widespread biological
      significance (Forgac, M. (1999) J. Biol. Chem. 274, 12951-12954). We now ascribe
      just such a regulatory function to the increases in cellular levels of inositol
      3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P(4)) that inevitably accompany activation
      of the ubiquitous Ins(1,4,5)P(3) signaling pathway. We used confocal imaging to
      record insulin granule acidification in single mouse pancreatic beta-cells.
      Granule acidification was reduced by perfusion of single cells with 10 microm
      Ins(3,4,5,6)P(4) (the concentration following receptor activation), whereas at 1
      microm ("resting" levels), Ins(3,4,5,6)P(4) was ineffective. This response to
      Ins(3,4,5,6)P(4) was not mimicked by 100 microm Ins(1,4,5,6)P(4) or by 100 microm
      Ins(1,3,4,5,6)P(5). Ins(3,4,5,6)P(4) did not affect granular H(+)-ATPase activity
      or H(+) leak, indicating that Ins(3,4,5,6)P(4) instead inhibited charge
      neutralization by ClC. The Ins(3,4,5,6)P(4)-mediated inhibition of vesicle
      acidification reduced exocytic release of insulin as determined by whole-cell
      capacitance recordings. This may impinge upon type 2 diabetes etiology.
      Regulatory control over vesicle acidification by this negative signaling pathway
      in other cell types should be considered.

PMID- 12055182
TI  - Silencing of the mouse H-rev107 gene encoding a class II tumor suppressor by CpG
      methylation.
AB  - H-rev107 is a tumor suppressor originally isolated in revertants of H-ras
      transformed cell lines. The gene is ubiquitously expressed in normal tissues but
      down-regulated in primary carcinomas or in many cell lines derived from tumors,
      including WEHI 7.1 lymphoma cells. Here, we show that unlike in H-rev107
      expressing cells or tissues the 5'-end of H-rev107 containing a CpG-rich region
      of 421 bp is highly methylated in WEHI 7.1 lymphoma cells, correlating with
      silencing of this gene. Repression of H-rev107 transcription in these cells could
      be relieved by chemically induced hypomethylation with 5-aza-dC. In addition,
      upon in vitro methylation, expression of the luciferase reporter gene driven by
      the H-rev107 promoter decreased by 80% in WEHI 7.1 and 293 cells. Furthermore, co
      transfection of the methyl-CpG binding proteins, MeCP2 and MBD2, inhibited H
      rev107 promoter activity up to 70% in SL2 cells when the promoter was methylated.
      By chromatin immunoprecipitation assays, we observed in vivo binding of MeCP2 and
      MBD2 to the 5'-end of H-rev107 in WEHI 7.1 cells, which was reduced to
      undetectable levels upon 5-aza-dC treatment, concluding that MeCP2 and MBD2 might
      be involved in silencing the methylated H-rev107 gene in lymphoma cells and
      probably certain tumors.

PMID- 12055183
TI  - Loss of androgen receptor transcriptional activity at the G(1)/S transition.
AB  - Androgens are essential for the differentiation, growth, and maintenance of male
      specific organs. The effects of androgens in cells are mediated by the androgen
      receptor (AR), a member of the nuclear receptor superfamily of transcription
      factors. Recently, transient transfection studies have shown that overexpression
      of cell cycle regulatory proteins affects the transcriptional activity of the AR.
      In this report, we characterize the transcriptional activity of endogenous AR
      through the cell cycle. We demonstrate that in G0, AR enhances transcription from
      an integrated steroid-responsive mouse mammary tumor virus promoter and also from
      an integrated androgen-specific probasin promoter. This activity is strongly
      reduced or abolished at the G(1)/S boundary. In S phase, the receptor regains
      activity, indicating that there is a transient regulatory event that inactivates
      the AR at the G(1)/S transition. This regulation is specific for the AR, since
      the related glucocorticoid receptor is transcriptionally active at the G(1)/S
      boundary. Not all of the effects of androgens are blocked, however, since
      androgens retain the ability to increase AR protein levels. The transcriptional
      inactivity of the AR at the G(1)/S junction coincides with a decrease in AR
      protein level, although activity can be partly rescued without an increase in
      receptor. Inhibition of histone deacetylases brings about this partial
      restoration of AR activity at the G(1)/S boundary, demonstrating the involvement
      of acetylation pathways in the cell cycle regulation of AR transcriptional
      activity. Finally, a model is proposed that explains the inactivity of the AR at
      the G(1)/S transition by integrating receptor levels, the action of cell cycle
      regulators, and the contribution of histone acetyltransferase-containing
      coactivators.

PMID- 12055184
TI  - Physical and functional interaction of HIV-1 Tat with E2F-4, a transcriptional
      regulator of mammalian cell cycle.
AB  - Tat protein of the human immunodeficiency virus type-1 (HIV-1) plays a critical
      role in the regulation of viral transcription and replication. In addition, Tat
      regulates the expression of a variety of cellular genes and could account for
      AIDS-associated diseases including Kaposi's Sarcoma and non-Hodgkin's lymphoma by
      interfering with cellular processes such as proliferation, differentiation, and
      apoptosis. The molecular mechanisms underlying the pleiotropic activities of Tat
      may include the generation of functional heterodimers of Tat with cellular
      proteins. By screening a human B-lymphoblastoid cDNA library in the yeast two
      hybrid system, we identified E2F-4, a member of E2F family of transcription
      factors, as a Tat-binding protein. The interaction between Tat and E2F-4 was
      confirmed by GST pull-down experiments performed with cellular extracts as well
      as with in vitro translated E2F-4. The physical association of Tat and E2F-4 was
      confirmed by in vivo binding experiments where Tat.E2F-4 heterodimers were
      recovered from Jurkat cells by immunoprecipitation and immunoblotting. By using
      plasmids expressing mutant forms of Tat and E2F-4, the domains involved in
      Tat.E2F-4 interaction were identified as the regions encompassing amino acids 1
      49 of Tat and amino acids 1-184 of E2F-4. Tat x E2F-4 complexes were shown to
      bind to E2F cis-regions with increased efficiency compared with E2F-4 alone and
      to mediate the activity of E2F-dependent promoters including HIV-1 long terminal
      repeat and cyclin A. The data point to Tat as an adaptor protein that recruits
      cellular factors such as E2F-4 to exert its multiple biological activities.

PMID- 12055185
TI  - Low Mr phosphotyrosine protein phosphatase associates and dephosphorylates p125
      focal adhesion kinase, interfering with cell motility and spreading.
AB  - Low M(r) phosphotyrosine protein phosphatase interferes in vivo with the
      activation of several growth factor receptors and is transiently redistributed,
      following cell stimulation with platelet-derived growth factor, from the cytosol
      to the cytoskeleton. We demonstrate here that this phosphatase also participates
      in the regulation of cell spreading and migration, pointing to its involvement in
      cytoskeleton organization. Low M(r) phosphotyrosine protein phosphatase
      overexpressing fibroblasts are, indeed, less spread than controls and display a
      significantly decreased number of focal adhesions and increased cell motility.
      Furthermore, p125 focal adhesion kinase is associated to, and dephosphorylated
      by, low M(r) phosphotyrosine protein phosphatase both in vitro and in vivo. This
      event is consistent with an altered association of pp60(src) with focal adhesion
      kinase. The activation of extracellular signal-regulated kinase, another well
      known event downstream of the focal adhesion kinase, is also affected. On the
      other hand, cells overexpressing the dominant-negative form of low M(r)
      phosphotyrosine protein phosphatase exhibit hyperphosphorylated focal adhesion
      kinase, reduced motility, and an increased number of focal adhesions, which are
      distributed all over the ventral cell surface. Taken together, the results
      reported here are in keeping with low M(r) phosphotyrosine protein phosphatase
      participation in FAK-mediated focal adhesion remodeling.

PMID- 12055186
TI  - Chemical identification of a low abundance lysozyme peptide family bound to I-Ak
      histocompatibility molecules.
AB  - The processing by antigen-presenting cells (APC) of the protein hen egg-white
      lysozyme (HEL) results in the selection of a number of peptide families by the
      class II major histocompatibility complex (MHC) molecule, I-A(k). Some of these
      families are expressed in very small amounts, in the order of a few
      picomoles/10(9) APC. We detected these peptides from an extract of class II MHC
      molecules by using monoclonal anti-peptide antibodies to capture the MHC-bound
      peptides prior to their examination by HPLC tandem mass spectrometry. Here, we
      have identified several members of a family of peptides encompassing residues 20
      35, which represent less than 1% of the total HEL peptides. Binding analysis
      indicated that the core segment of the family was represented by residues 24-32
      (SLGNWVCAA). Asn-27 (shown in boldface) is the main MHC-binding residue, mapped
      as interacting with the P4 pocket of the I-A(k) molecule. Analysis of several T
      cell hybridomas indicated that three residues contacted the T cell receptor: Tyr
      23 (P-1), Leu-25 (P3), and Trp-28 (P5). The HEL peptides isolated from the APC
      extract were sulfated on Tyr-23, but further analysis showed that this
      modification did not occur physiologically but took place during the peptide
      isolation.

PMID- 12055187
TI  - Molecular kinetics of nerve growth factor receptor trafficking and activation.
AB  - A growing body of evidence indicates a close relationship between tyrosine kinase
      receptor trafficking and signaling. Biochemical and molecular analyses of the
      expression, fate, and kinetics of membrane trafficking of the nerve growth factor
      (NGF) receptor TrkA were performed in PC12 cells. Pulse-chase experiments
      indicate that TrkA is synthesized as a 110-kDa N-glycosylated precursor that
      leads to the mature 140-kDa form of the receptor with a half-life of conversion
      of approximately 24 +/- 0.5 min. Neuraminidase digestion shows that modification
      of the carbohydrate moiety of the receptor by sialylation occurs during
      maturation. The 140-kDa form is rapidly translocated to the cell surface as
      assessed by cell surface biotinylation performed on intact PC12 cells. Mature
      receptor half-life is approximately 138 +/- 4 min and is shortened to 86 +/- 8
      min by NGF treatment. Flow cytometric analysis indicates that NGF induces
      clearing of this receptor from the cell surface within minutes of treatment. The
      addition of NGF decreases the half-life of cell surface gp140(TrkA) from 100 to
      35 min and leads to enhanced lysosomal degradation of the receptor. The process
      of NGF-induced TrkA internalization is clearly affected by interfering with
      ligand binding to p75(NTR). An analysis of receptor activation kinetics also
      shows that receptor signaling primarily takes place from an intracellular
      location. Together, these data show that the primary effect of NGF treatment is a
      p75(NTR)-modulated decrease in TrkA transit time at the cell surface.

PMID- 12055188
TI  - The effects of reactive site location on the inhibitory properties of the serpin
      alpha(1)-antichymotrypsin.
AB  - The large size of the serpin reactive site loop (RSL) suggests that the role of
      the RSL in protease inhibition is more complex than that of presenting the
      reactive site (P1 residue) to the protease. This study examines the effect on
      inhibition of relocating the reactive site (Leu-358) of the serpin alpha(1)
      antichymotrypsin either one residue closer (P2) or further (P1') from the base of
      the RSL (Glu-342). alpha(1)-Antichymotrypsin variants were produced by mutation
      within the P4-P2' region; the sequence ITLLSA was changed to ITLSSA to relocate
      the reactive site to P2 (Leu-357) and to ITITLS to relocate it to P1' (Leu-359).
      Inhibition of the chymotrypsin-like proteases human chymase and chymotrypsin and
      the non-target protease human neutrophil elastase (HNE) were analyzed. The P2
      variant inhibited chymase and chymotrypsin but not HNE. Relative to P1,
      interaction at P2 was characterized by greater complex stability, lower
      inhibition rate constants, and increased stoichiometry of inhibition values. In
      contrast, the P1' variant inhibited HNE (stoichiometry of inhibition = 4) but not
      chymase or chymotrypsin. However, inhibition of HNE was by interaction with Ile
      357, the P2 residue. The P1' site was recognized by all proteases as a cleavage
      site. Covalent-complexes resistant to SDS-PAGE were observed in all inhibitory
      reactions, consistent with the trapping of the protease as a serpin-acyl protease
      complex. The complete loss in inhibitory activity associated with lengthening the
      Glu-342-reactive site distance by a single residue and the enhanced stability of
      complexes associated with shortening this distance by a single residue are
      compatible with the distorted-protease model of inhibition requiring full
      insertion of the RSL into the body of the serpin and translocation of the linked
      protease to the pole opposite from that of encounter.

PMID- 12055189
TI  - Syndecan-2 mediates adhesion and proliferation of colon carcinoma cells.
AB  - Syndecan-2 is a transmembrane heparan sulfate proteoglycan whose function at the
      cell surface is unclear. In this study, we examined the function of syndecan-2 in
      colon cancer cell lines. In several colon cancer cell lines, syndecan-2 was
      highly expressed compared with normal cell lines. In contrast, syndecan-1 and -4
      were decreased. Cell biological studies using the extracellular domain of
      recombinant syndecan-2 (2E) or spreading assay with syndecan-2 antibody-coated
      plates showed that syndecan-2 mediated adhesion and cytoskeletal organization of
      colon cancer cells. This interaction was critical for the proliferation of colon
      carcinoma cells. Blocking with 2E or antisense syndecan-2 cDNA induced G(0)/G(1)
      cell cycle arrest with concomitantly increased expression of p21, p27, and p53.
      Furthermore, blocking of syndecan-2 through antisense syndecan-2 cDNA
      significantly reduced tumorigenic activity in colon carcinoma cells. Therefore,
      increased syndecan-2 expression appears to be a critical for colon carcinoma cell
      behavior, and syndecan-2 regulates tumorigenic activity through regulation of
      adhesion and proliferation in colon carcinoma cells.

PMID- 12055191
TI  - Ligand exchange between proteins. Exchange of biotin and biotin derivatives
      between avidin and streptavidin.
AB  - We have studied the structural elements that affect ligand exchange between the
      two high affinity biotin-binding proteins, egg white avidin and its bacterial
      analogue, streptavidin. For this purpose, we have developed a simple assay based
      on the antipodal behavior of the two proteins toward hydrolysis of biotinyl p
      nitrophenyl ester (BNP). The assay provided the experimental basis for these
      studies. It was found that biotin migrates unidirectionally from streptavidin to
      avidin. Conversely, the biotin derivative, BNP, is transferred in the opposite
      direction, from avidin to streptavidin. A previous crystallographic study
      (Huberman, T., Eisenberg-Domovich, Y., Gitlin, G., Kulik, T., Bayer, E. A.,
      Wilchek, M., and Livnah, O. (2001) J. Biol. Chem. 276, 32031-32039) provided
      insight into a plausible explanation for these results. These data revealed that
      the non-hydrolyzable BNP analogue, biotinyl p-nitroanilide, was almost completely
      sheltered in streptavidin as opposed to avidin in which the disordered
      conformation of a critical loop resulted in the loss of several hydrogen bonds
      and concomitant exposure of the analogue to the solvent. In order to determine
      the minimal modification of the biotin molecule required to cause the disordered
      loop conformation, the structures of avidin and streptavidin were determined with
      norbiotin, homobiotin, and a common long-chain biotin derivative, biotinyl
      epsilon-aminocaproic acid. Six new crystal structures of the avidin and
      streptavidin complexes with the latter biotin analogues and derivatives were thus
      elucidated. It was found that extending the biotin side chain by a single CH(2)
      group (i.e. homobiotin) is sufficient to result in this remarkable conformational
      change in the loop of avidin. These results bear significant biotechnological
      importance, suggesting that complexes containing biotinylated probes with
      streptavidin would be more stable than those with avidin. These findings should
      be heeded when developing new drugs based on lead compounds because it is
      difficult to predict the structural and conformational consequences on the
      resultant protein-ligand interactions.

PMID- 12055190
TI  - Increased spreading, Rac/p21-activated kinase (PAK) activity, and compromised
      cell motility in cells deficient in vasodilator-stimulated phosphoprotein (VASP).
AB  - Ena/VASP (Drosophila Enabled/vasodilator-stimulated phosphoprotein) proteins are
      key regulators that promote or inhibit actin-based motility, cell adhesion, and
      various aspects of axon guidance. However, a conclusive concept of Ena/VASP
      functions remains elusive. Here, we report that VASP-deficient fibroblasts,
      despite normal mammalian Enabled (Mena) and Ena-VASP-like (Evl) expression
      levels, are highly spread. VASP(-/-) cells cover about twice the substrate
      surface area as wild type cells, while cell volumes are unchanged. In accordance
      with these observations, activation of the Rac/p21-activated kinase (PAK)
      pathway, a crucial element in the regulation of cell spreading, is markedly
      enhanced in VASP(-/-) cells. Thus, in the absence of VASP Rac activation is
      dramatically prolonged, and PAK activity is elevated after stimulation with
      platelet-derived growth factor or serum, respectively. Moreover, VASP-deficient
      cells show compromised migration and reorientation in a wound healing assay.
      Collectively, our results reveal a VASP-dependent modulation of the Rac/PAK
      pathway and Rac/PAK-regulated processes, like cell motility and polarization.

PMID- 12055192
TI  - Xenopus actin-interacting protein 1 (XAip1) enhances cofilin fragmentation of
      filaments by capping filament ends.
AB  - Xenopus actin-interacting protein 1 (XAip1) is thought to promote fragmentation
      of actin filaments by cofilin. To examine the mechanism of XAip1, we measured
      polymer lengths by fluorescence microscopy and the concentration of filament ends
      with an elongation assay. Cofilin creates ends by severing actin filaments. XAip1
      alone does not sever actin filaments or prevent annealing/redistribution of
      mechanically severed filaments and has no effect on the concentration of ends
      available for subunit addition. In the presence of XAip1, the apparent filament
      fragmentation by cofilin is enhanced, but XAip1 reduces rather than increases the
      concentration of ends capable of adding subunits. Electron microscopy with gold
      labeled antibodies showed that a low concentration of XAip1 bound preferentially
      to one end of the filament. A high concentration of XAip1 bound along the length
      of the filament. In the presence of gelsolin-actin to cap filament barbed ends,
      XAip1 does not enhance cofilin activity. We conclude that XAip1 caps the barbed
      end of filaments severed by cofilin. This capping blocks annealing and
      depolymerization and allows more extensive severing by cofilin.

PMID- 12055193
TI  - Transcriptional profiling of bone regeneration. Insight into the molecular
      complexity of wound repair.
AB  - The healing of skeletal fractures is essentially a replay of bone development,
      involving the closely regulated, interdependent processes of chondrogenesis and
      osteogenesis. Using a rat femur model of bone healing to determine the degree of
      transcriptional complexity of these processes, suppressive subtractive
      hybridization (SSH) was performed between RNA isolated from intact bone to that
      of callus from post-fracture (PF) days 3, 5, 7, and 10 as a means of identifying
      up-regulated genes in the regenerative process. Analysis of 3,635 cDNA clones
      revealed 588 known genes (65.8%, 2392 clones) and 821 expressed sequence tags
      (ESTs) (31%, 1,127). The remaining 116 cDNAs (3.2%) yielded no homology and
      presumably represent novel genes. Microarrays were then constructed to confirm
      induction of expression and determine the temporal profile of all isolated cDNAs
      during fracture healing. These experiments confirmed that approximately 90 and
      approximately 80% of the subtracted known genes and ESTs are up-regulated (> or =
      2.5-fold) during the repair process, respectively. Clustering analysis revealed
      subsets of genes, both known and unknown, that exhibited distinct expression
      patterns over 21 days (PF), indicating distinct roles in the healing process.
      Additionally, this transcriptional profiling of bone repair revealed a host of
      activated signaling molecules and even pathways (i.e. Wnt). In summary, the data
      demonstrate, for the fist time, that the healing process is exceedingly complex,
      involves thousands of activated genes, and indicates that groups of genes rather
      than individual molecules should be considered if the regeneration of bone is to
      be accelerated exogenously.

PMID- 12055194
TI  - Sp1 and Sp3 transcription factors mediate malondialdehyde-induced collagen alpha
      1(I) gene expression in cultured hepatic stellate cells.
AB  - Malondialdehyde, the end product of lipid peroxidation, has been shown to
      stimulate collagen alpha1(I) (Col1a1) gene expression. However, mechanisms of
      this effect are unclear. The purpose of this study was to clarify these
      mechanisms. Rat hepatic stellate cells were cultured in the presence of 200
      microm malondialdehyde, and the effects on collagen gene expression and the
      binding of nuclear proteins to the col1a1 promoter were analyzed. Malondialdehyde
      treatment induced an increase in the cellular levels of col1a1 mRNA that was
      abrogated by pretreating cells with cycloheximide, p-hydroxymercuribenzoate,
      pyridoxal 5'-phosphate, and mithramycin. Transient transfections showed that
      malondialdehyde exerted its effect through regulatory elements located between 
      220 and -110 bp of the col1a1 promoter. Gel retardation assays demonstrated that
      malondialdehyde increased the binding of nuclear proteins to two elements located
      between -161 and -110 bp of the col1a1 promoter. These bindings were supershifted
      with Sp1 and Sp3 antibodies. Finally, malondialdehyde increased cellular levels
      of the Sp1 and Sp3 proteins and Sp1 mRNA. Our data indicated that treatment of
      hepatic stellate cells with malondialdehyde stimulated col1a1 gene expression by
      inducing the synthesis of Sp1 and Sp3 and their binding to two regulatory
      elements located between -161 and -110 bp of the col1a1 promoter.

PMID- 12055195
TI  - Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated
      by the peroxisome proliferator-activated receptor alpha.
AB  - The apical sodium-dependent bile salt transporter (ASBT/SLC10A2), also called the
      ileal bile acid transporter, mediates the intestinal absorption of bile salts.
      The efficiency of this transport process is a determinant of hepatic bile salt
      synthesis from cholesterol and of serum triglyceride levels. Our aim was to
      characterize the human ASBT gene promoter with respect to regulatory mechanisms
      that coordinately affect ASBT expression and hepatic lipid and bile salt
      metabolism. The minimal construct that confers full promoter activity contains
      three functional hepatocyte nuclear factor 1alpha (HNF1alpha) recognition sites,
      explaining the dependence of ASBT gene expression upon HNF1alpha. A nuclear
      receptor binding site arranged as a direct hexanucleotide repeat (DR1 motif) is
      localized approximately 1.6 kb upstream of the transcription initiation site.
      Constructs containing this element were transactivated by WY14643 and
      ciprofibrate, ligands of the peroxisome proliferator-activated receptor alpha
      (PPARalpha), in Caco2 cells. The DR1 element was shown to bind the PPARalpha/9
      cis-retinoic acid receptor heterodimer, and targeted mutagenesis of the DR1 motif
      abolished PPARalpha responsiveness. Ciprofibrate treatment of SK-ChA
      cholangiocytes increased ASBT mRNA levels, suggesting a physiologic role for
      PPARalpha-mediated ASBT gene regulation. This study identifies PPARalpha as a
      novel link between ileal bile salt absorption and hepatic lipid metabolism.

PMID- 12055196
TI  - A novel single amino acid deletion caspase-8 mutant in cancer cells that lost
      proapoptotic activity.
AB  - Caspase-8 is an important initiation caspase that activates the caspase cascade
      during death receptor-mediated apoptosis. We here report a novel caspase-8 mutant
      with a naturally occurring deletion of leucine 62 (Delta Leu62casp-8). Delta
      Leu62casp-8 has a shorter half-life than its wild-type counterpart. Unlike wild
      type caspase-8, Delta Leu62casp-8 failed to interact with wild-type caspase-8 or
      with the adaptor protein FADD. Delta Leu62casp-8 lost its proapoptotic activity
      in mammalian cells. The leucine 62 therefore is critical for caspase-8 function,
      and the mutation may be one of the mechanisms through which some types of cancer
      cells escape from programmed cell death.

PMID- 12055197
TI  - Induction of apoptosis by protein kinase C delta is independent of its kinase
      activity.
AB  - Protein kinase C, a multigene family of phospholipid-dependent and diacylglycerol
      activated Ser/Thr protein kinases, is a key component in many signal transduction
      pathways. The kinase activity was thought to be essential for a plethora of
      biological processes attributed to these enzymes. Here we show that at least one
      protein kinase C function, the induction of apoptosis by protein kinase C delta,
      is independent of the kinase activity. Stimulation of green fluorescent protein
      protein kinase C delta fusion protein with phorbol ester or diacylglycerol led to
      its redistribution within seconds after the stimulus. Membrane blebbing, an early
      hallmark of apoptosis, was visible as early as 20 min after stimulation, and
      nuclear condensation was visible after 3-5 h. Apoptosis could be inhibited by
      expression of Bcl-2 but not by specific protein kinase C inhibitors. In addition,
      a kinase-negative mutant of protein kinase C delta also induced apoptosis to the
      same extent as the wild type enzyme. Apoptosis was confined to the protein kinase
      C delta-overexpressing cells. Stimulation of overexpressed protein kinase C
      epsilon did not result in increased apoptosis. Our results indicate that distinct
      protein kinase C isozymes induce apoptosis in vascular smooth muscle cells. More
      importantly, they show that some protein kinase C effector functions are
      independent of the catalytic activity.

PMID- 12055198
TI  - Proteolytic Cleavage of the Linker Region of the Human P-glycoprotein Modulates
      Its ATPase Function.
AB  - P-glycoprotein (Pgp), an anticancer drug-translocating ATPase, is responsible for
      multidrug resistance in cancer. We have previously shown (Nuti, S. L., Mehdi, A.,
      and Rao, U. S. (2000) Biochemistry 39, 3424-3432) that tryptic cleavage of Pgp
      results in the activation of basal and drug-stimulated ATPase functions of Pgp.
      To understand this phenomenon, we determined the sites cleaved by trypsin and
      further examined whether the modulation of Pgp function is trypsin-specific or
      the result of proteolysis in general. The effects of chymotrypsin and proteinase
      K on Pgp ATPase function were studied. The results show that proteolysis of Pgp
      irrespective of the protease employed resulted in the activation of basal ATPase
      activity. However, drug-stimulated ATPase activities were differentially
      modulated. Immunoblot analysis of proteolytic digests indicated that,
      irrespective of the protease employed, Pgp was predominantly cleaved in the
      middle of the molecule. N-terminal amino acid sequencing of Pgp tryptic and
      chymotryptic peptides indicated Arg(680) and Leu(682) as the sites of cleavage,
      respectively. These two cleavage sites are part of the predicted linker region
      that joins the two halves of Pgp. Together, these results suggest that the linker
      region in Pgp is primarily accessible to protease action and that cleavage of
      this region modulates Pgp ATPase function.

PMID- 12055200
TI  - Regulation of Wnt signaling during adipogenesis.
AB  - We have identified Wnt10b as a potent inhibitor of adipogenesis that must be
      suppressed for preadipocytes to differentiate in vitro. Here, we demonstrate that
      a specific inhibitor of glycogen synthase kinase 3, CHIR 99021, mimics Wnt
      signaling in preadipocytes. CHIR 99021 stabilizes free cytosolic beta-catenin and
      inhibits adipogenesis by blocking induction of CCAAT/enhancer-binding protein
      alpha and peroxisome proliferator-activated receptor gamma. Preadipocyte
      differentiation is inhibited when 3T3-L1 cells are exposed to CHIR 99021 for any
      24 h period during the first 3 days of adipogenesis. Consistent with this time
      frame of inhibition, expression of Wnt10b mRNA is suppressed upon induction of
      differentiation, with a 50% decline by 6 h and complete inhibition by 36 h. Of
      the agents used to induce differentiation, exposure of 3T3-L1 cells to methyl
      isobutylxanthine or cAMP is sufficient to suppress expression of Wnt10b mRNA.
      Inhibition of adipogenesis by Wnt10b is likely mediated by Wnt receptors,
      Frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor
      related proteins 5 and 6. These receptors, like Wnt10b, are highly expressed in
      preadipocytes and stromal vascular cells. Finally, we demonstrate that disruption
      of extracellular Wnt signaling by expression of secreted Frizzled related
      proteins causes spontaneous adipocyte conversion.

PMID- 12055199
TI  - Sucrase is an intramolecular chaperone located at the C-terminal end of the
      sucrase-isomaltase enzyme complex.
AB  - The sucrase-isomaltase enzyme complex (pro-SI) is a type II integral membrane
      glycoprotein of the intestinal brush border membrane. Its synthesis commences
      with the isomaltase (IM) subunit and ends with sucrase (SUC). Both domains reveal
      striking structural similarities, suggesting a pseudo-dimeric assembly of a
      correctly folded and an enzymatically active pro-SI. The impact of each domain on
      the folding and function of pro-SI has been analyzed by individual expression and
      coexpression of the individual subunits. SUC acquires correct folding, enzymatic
      activity and transport competence and is secreted into the external milieu
      independent of the presence of IM. By contrast, IM persists as a mannose-rich
      polypeptide that interacts with the endoplasmic reticulum resident molecular
      chaperone calnexin. This interaction is disrupted when SUC is coexpressed with
      IM, indicating that SUC competes with calnexin for binding of IM. The interaction
      between SUC and the membrane-anchored IM leads to maturation of IM and blocks the
      secretion of SUC into the external milieu. We conclude that SUC plays a role as
      an intramolecular chaperone in the context of the pro-SI protein. To our
      knowledge all intramolecular chaperones so far identified are located at the N
      terminal end. SUC is therefore the first C-terminally located intramolecular
      chaperone in mammalian cells.

PMID- 12055201
TI  - On glutathione. II. A thermostable oxidation-reduction system (Hopkins, F. G.,
      and Dixon, M. (1922) J. Biol. Chem. 54, 527-563).

PMID- 12055202
TI  - Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not
      sufficient, for induction of organ-specific autoimmune disease.
AB  - Thymectomy of BALB/c mice on day 3 of life results in the development of
      autoimmune gastritis (AIG) due to the absence of CD4(+)CD25(+) regulatory T
      cells. However, depletion of CD4(+)CD25(+) T cells by treatment with anti-CD25
      rarely resulted in AIG. Depletion was efficient, as transfer of splenocytes from
      depleted mice induced AIG in nu/nu mice. One explanation for this result is that
      CD4(+)CD25(-) T cells upon transfer to nude recipients undergo lymphopenia
      induced proliferation, providing a signal for T cell activation. Cotransfer of
      CD25(+) T cells did not inhibit initial proliferation but did suppress AIG.
      Surprisingly, immunization with the AIG target Ag, H/K ATPase, in IFA failed to
      induce disease in normal animals but induced severe AIG in CD25-depleted mice.
      These results demonstrate that second signals (nonspecific proliferation, TCR
      activation, or inflammation) are needed for induction of autoimmunity in the
      absence of CD25(+) regulatory T cells.

PMID- 12055203
TI  - Cutting edge: activation of the p38 mitogen-activated protein kinase signaling
      pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia.
AB  - Myelosuppressive cytokines, in particular IFN-gamma and TNF-alpha, play an
      important role in the pathogenesis of idiopathic aplastic anemia in humans. It is
      unknown whether these negative regulators of hemopoiesis suppress stem cells by
      activating a common signaling cascade or via distinct nonoverlapping pathways. In
      this study, we provide evidence that a common element in signaling for IFN-gamma
      and TNF-alpha in human hemopoietic progenitors is the p38/MapKapK-2 signaling
      cascade. Our studies indicate that pharmacological inhibition of p38 reverses the
      suppressive effects of IFN-gamma and TNF-alpha on normal human bone marrow
      derived erythroid and myeloid progenitors. Most importantly, inhibition of p38
      strongly enhances hemopoietic progenitor colony formation from aplastic anemia
      bone marrows in vitro. Thus, p38 appears to play a critical role in the
      pathogenesis of aplastic anemia, suggesting that selective pharmacological
      inhibitors of this kinase may prove useful in the treatment of aplastic anemia
      and other cytokine-mediated bone marrow failure syndromes.

PMID- 12055204
TI  - Cutting edge: the immunostimulatory activity of the lung surfactant protein-A
      involves Toll-like receptor 4.
AB  - The collectin surfactant protein-A (SP-A) is involved in the innate host defense
      and the regulation of inflammatory processes in the lung. In this work we
      investigated the molecular mechanisms related to the immunostimulatory activity
      of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation
      in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary
      cells. We demonstrate that SP-A-induced activation of the NF-kappaB signaling
      pathway and up-regulation of cytokine synthesis such as TNF-alpha and IL-10 are
      critically dependent on the TLR4 functional complex. These findings support the
      concept that TLR4 is a pattern recognition receptor that signals in response to
      both foreign pathogens and endogenous host mediators.

PMID- 12055205
TI  - Cutting edge: BLyS enables survival of transitional and mature B cells through
      distinct mediators.
AB  - These studies characterize BLyS responsiveness and receptor expression among
      transitional and mature peripheral B cells. The results show a maturation
      associated increase in BLyS binding capacity that reflects differential
      expression patterns of the three BLyS receptors. Accordingly, BLyS administration
      enlarges only late transitional and mature peripheral B (MB) cell compartments.
      Furthermore, bromodeoxyuridine labeling and cell cycle analyses show these
      effects are mediated through enhanced proportional survival of cells traversing
      the T2, T3, and MB cell stages, rather than by causing proliferation or slowing
      transit within these subsets. Despite similar effects on survival, BLyS up
      regulates the antiapoptotic genes A1 and bcl-x(L) in MB cells but not immature B
      cells. Together, these findings show that, while BLyS influences B cell survival
      in several peripheral differentiation subsets, the downstream mediators differ,
      thus providing the first direct evidence for an established B lineage survival
      system whose intermediates change as B cells mature.

PMID- 12055206
TI  - Cutting edge: MyD88 is required for resistance to Toxoplasma gondii infection and
      regulates parasite-induced IL-12 production by dendritic cells.
AB  - Host resistance to the intracellular protozoan Toxoplasma gondii is highly
      dependent on early IL-12 production by APC. We demonstrate here that both host
      resistance and T. gondii-induced IL-12 production are dramatically reduced in
      mice lacking the adaptor molecule MyD88, an important signaling element used by
      Toll-like receptor (TLR) family members. Infection of MyD88-deficient mice with
      T. gondii resulted in uncontrolled parasite replication and greatly reduced
      plasma IL-12 levels. Defective IL-12 responses to T. gondii Ags (soluble
      tachyzoite Ag (STAg)) were observed in MyD88(-/-) peritoneal macrophages,
      neutrophils, and splenic dendritic cells (DC). In contrast, DC from TLR2- or TLR4
      deficient animals developed normal IL-12 responses to STAg. In vivo treatment
      with pertussis toxin abolished the residual IL-12 response displayed by STAg
      stimulated DC from MyD88(-/-) mice. Taken together, these data suggest that the
      induction of IL-12 by T. gondii depends on a unique mechanism involving both
      MyD88 and G protein-coupled signaling pathways.

PMID- 12055207
TI  - Cutting edge: urease release by Helicobacter pylori stimulates macrophage
      inducible nitric oxide synthase.
AB  - Inducible NO synthase (iNOS) expression and production of NO are both up
      regulated with Helicobacter pylori infection in vivo and in vitro. We determined
      whether major pathogenicity proteins released by H. pylori activate iNOS by
      coculturing macrophages with wild-type or mutant strains deficient in VacA, CagA,
      picB product, or urease (ureA(-)). When filters were used to separate H. pylori
      from macrophages, there was a selective and significant decrease in stimulated
      iNOS mRNA, protein, and NO(2)(-) production with the ureA(-) strain compared with
      wild-type and other mutants. Similarly, macrophage NO(2)(-) generation was
      increased by H. pylori protein water extracts of all strains except ureA(-).
      Recombinant urease stimulated significant increases in macrophage iNOS expression
      and NO(2)(-) production. Taken together, these findings indicate a new role for
      the essential H. pylori survival factor, urease, implicating it in NO-dependent
      mucosal damage and carcinogenesis.

PMID- 12055208
TI  - Cutting edge: V alpha 14-J alpha 281 NKT cells naturally regulate experimental
      autoimmune encephalomyelitis in nonobese diabetic mice.
AB  - Although deficiencies in the NKT cell population have been observed in multiple
      sclerosis and mouse strains susceptible to experimental autoimmune
      encephalomyelitis (EAE), little is known about the function of these cells in CNS
      autoimmunity. In this work we report that TCR Valpha14-Jalpha281 transgenic
      nonobese diabetic mice, which are enriched in CD1d-restricted NKT cells, are
      protected from EAE. The protection is associated with a striking inhibition of Ag
      specific IFN-gamma production in the spleen, implying modulation of the
      encephalitogenic Th1 response. This modulation is independent of IL-4 because IL
      4-deficient Valpha14-Jalpha281 mice are still protected against EAE and
      independent of NKT cell-driven Th1 to Th2 deviation, because no increased
      autoantigen-specific Th2 response was observed in immunized Valpha14-Jalpha281
      transgenic mice. Our findings indicate that enrichment and/or stimulation of CD1d
      dependent NKT cells may be used as a novel strategy to treat CNS autoimmunity.

PMID- 12055209
TI  - T and B cell recovery in arthritis adoptively transferred to SCID mice: antigen
      specific activation is required for restoration of autopathogenic CD4+ Th1 cells
      in a syngeneic system.
AB  - T cell homeostasis is a physiological function of the immune system that
      maintains a balance in the numbers and ratios of T cells at the periphery. A self
      MHC/self-peptide ligand can induce weak (covert) signals via the TCR, thus
      providing an extended lifespan for naive T cells. A similar mechanism is
      responsible for the restoration of immune homeostasis in severe lymphopenic
      conditions such as those following irradiation or chemotherapy, or upon transfer
      of lymphocytes to nu/nu or SCID mice. To date, the genetic backgrounds of donor
      and recipient SCID mice were unmatched in all autoimmune arthritis transfer
      experiments, and the recovery of lymphoid cells in the host has not been
      followed. In this study, we present the adoptive transfer of proteoglycan (PG)
      induced arthritis using unseparated and T or B cell-depleted lymphocytes from
      arthritic BALB/c donors to genetically matched syngeneic SCID recipient mice. We
      demonstrate that selectively recovered lymphoid subsets determine the clinical
      and immunological status of the recipient. We found that when T cells were
      depleted (>98% depleted), B cells did not produce PG-specific anti-mouse (auto)
      Abs unless SCID mice received a second Ag (PG) injection, which promoted the
      recovery of Ag-specific CD4(+) Th1 cells. Reciprocally, as a result of B cell
      recovery, high levels of serum anti-PG Abs were found in SCID mice that received
      B cell-depleted (>99% depleted) T lymphocytes. Our results indicate a selective
      and highly effective cooperation between CD4(+) T cells and B lymphocytes that is
      required for the restoration of pathological homeostasis and development of
      autoimmune arthritis in SCID mice.

PMID- 12055210
TI  - Dynamic regulation of T cell immunity by CD43.
AB  - During a viral response, Ag-specific effector T cells show dramatically increased
      binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated
      the contribution of CD43 expression to 1B11 and PNA binding as well as its role
      in generation and maintenance of a CD8 T cell response. Analysis of CD43(-/-)
      mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific
      CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the
      role of CD43 in the kinetics of an immune response. We show that CD43 expression
      modestly effects generation of a primary virus-specific CD8 T cell response in
      vivo but plays a more significant role in trafficking of CD8 T cells to tissues
      such as the brain. More interestingly, CD43 plays a role in the contraction of
      the immune response, with CD43(-/-) mice showing increased numbers of Ag-specific
      CD8 T cells following initial expansion. Following the peak of expansion, Ag
      specific CD8 T cells from -/- mice show similar proliferation but demonstrate
      increased Bcl-2 levels and decreased apoptosis of Ag-specific effector CD8 T
      cells in vitro. Consistent with a delay in the down-modulation of the immune
      response, following chronic viral infection CD43(-/-) mice show increased
      morbidity. These data suggest a dynamic role of CD43 during an immune response: a
      positive regulatory role in costimulation and trafficking of T cells to the CNS
      and a negative regulatory role in the down-modulation of an immune response.

PMID- 12055211
TI  - Antiviral immune responses in the absence of organized lymphoid T cell zones in
      plt/plt mice.
AB  - The paucity of lymph node (LN) T cells (plt) mutation in mice results in strongly
      reduced T cell numbers in LNs and homing defects of both dendritic cells (DCs)
      and naive T cells. In this study, we investigated the functional significance of
      the plt phenotype for the generation of antiviral immune responses against
      cytopathic and noncytopathic viruses. We found that DC-CD8(+) T cell contacts and
      the initial priming of virus-specific T cells in plt/plt mice occurred mainly in
      the marginal zone of the spleen and in the superficial cortex of LNs. The
      magnitude of the initial response and the maintenance of protective memory
      responses in plt/plt mice was only slightly reduced compared with plt/+ controls.
      Furthermore, plt/plt mice mounted rapid neutralizing antiviral B cell responses
      and displayed normal Ig class switch. Our data indicate that the defective homing
      of DCs and naive T cells resulting from the plt/plt mutation results in a small,
      but not significant, effect on the induction of protective antiviral T and B cell
      immunity. Overall, we conclude that the spatial organization of secondary
      lymphoid T cell zones via the CCR7-CC chemokine ligand 19/CC chemokine ligand 21
      pathway is not an absolute requirement for the initial priming and the
      maintenance of protective antiviral T and B cell responses.

PMID- 12055212
TI  - The protein product of the tumor suppressor gene, melanoma differentiation
      associated gene 7, exhibits immunostimulatory activity and is designated IL-24.
AB  - The melanoma differentiation-associated gene 7 (mda-7) has been studied primarily
      in the context of its tumor suppressor activity. Although mda-7 has been
      designated as IL-24 based on its gene location in the IL-10 locus and its mRNA
      expression in leukocytes, no functional evidence supporting this cytokine
      designation exists. To further characterize MDA-7/IL-24 expression patterns in
      the human immune system, MDA-7/IL-24 protein levels were examined in human PBMC.
      MDA-7/IL-24 was detected in PHA- and LPS-stimulated whole PBMC lysate by Western
      blot and in PHA-activated CD56 and CD19 subsets by immunohistochemistry. The
      biological function of MDA-7/IL-24, secreted from Ad-MDA7-transfected HEK 293
      cells, was assessed by examining the effect of MDA-7/IL-24 on the cytokine
      secretion profile of PBMC. Within 48 h MDA-7/IL-24 induced secretion of high
      levels of IL-6, TNF-alpha, and IFN-gamma and low levels of IL-1beta, IL-12, and
      GM-CSF from human PBMC as measured by ELISA. The MDA-7/IL-24-mediated induction
      of these Th1-type cytokines was inhibited by the addition of IL-10 to the PBMC
      cultures, suggesting that these two related protein family members may provide
      antagonistic functions. Therefore, because human blood leukocytes can be
      stimulated to produce MDA-7/IL-24, as well as respond to MDA-7/IL-24 by
      expressing secondary cytokines, MDA-7/IL-24 has the expression profile and major
      functional attributes that justify its designation as an IL.

PMID- 12055213
TI  - Viral abrogation of stem cell transplantation tolerance causes graft rejection
      and host death by different mechanisms.
AB  - Tolerance-based stem cell transplantation using sublethal conditioning is being
      considered for the treatment of human disease, but safety and efficacy remain to
      be established. We have shown that mouse bone marrow recipients treated with
      sublethal irradiation plus transient blockade of the CD40-CD154 costimulatory
      pathway develop permanent hematopoietic chimerism across allogeneic barriers. We
      now report that infection with lymphocytic choriomeningitis virus at the time of
      transplantation prevented engraftment of allogeneic, but not syngeneic, bone
      marrow in similarly treated mice. Infected allograft recipients also failed to
      clear the virus and died. Postmortem study revealed hypoplastic bone marrow and
      spleens. The cause of death was virus-induced IFN-alphabeta. The rejection of
      allogeneic bone marrow was mediated by a radioresistant CD8(+)TCR
      alphabeta(+)NK1.1(-) T cell population. We conclude that a noncytopathic viral
      infection at the time of transplantation can prevent engraftment of allogeneic
      bone marrow and result in the death of sublethally irradiated mice treated with
      costimulation blockade. Clinical application of stem cell transplantation
      protocols based on costimulation blockade and tolerance induction may require
      patient isolation to facilitate the procedure and to protect recipients.

PMID- 12055214
TI  - CD36 or alphavbeta3 and alphavbeta5 integrins are not essential for MHC class I
      cross-presentation of cell-associated antigen by CD8 alpha+ murine dendritic
      cells.
AB  - Cross-presentation of cell-associated Ag is thought to involve receptor-mediated
      uptake of apoptotic cells by dendritic cells (DC), and studies with human DC
      strongly implicate the endocytic receptor CD36 and the integrins alpha(v)beta(3)
      and/or alpha(v)beta(5) in this process. In the mouse, cross-presentation was
      recently shown to be a function of CD8alpha(+) DC. Here we report that CD36 is
      expressed on CD8alpha(+), but not on CD8alpha(-), DC. To address the role of CD36
      in cross-presentation we compared CD36(-/-) and CD36(+/+) H-2(b) DC for their
      ability to stimulate naive OT-1 T cells specific for OVA plus H-2K(b) in the
      presence of OVA-loaded MHC-mismatched splenocytes as a source of cell-associated
      Ag for cross-presentation. Surprisingly, no difference was seen between CD36(-/-)
      and CD36(+/+) CD8alpha(+) DC in their ability to cross-present cell-associated
      OVA or to capture OVA-bearing cells. Furthermore, the proliferation of CFSE
      labeled OT-1 cells in response to OVA cross-presentation in vivo was normal in
      CD36(-/-) bone marrow chimeras, also arguing against a necessary role for CD36 in
      cross-presentation by DC or other APC. DC doubly deficient for beta(3) and
      beta(5) integrins were similarly unimpaired in their ability to cross-present OVA
      bearing cells in vitro. These data demonstrate that in the mouse, receptors other
      than CD36 or beta(3) and beta(5) integrins can support the specialized cross
      presenting function of CD8alpha(+) DC.

PMID- 12055215
TI  - CD36 is differentially expressed by CD8+ splenic dendritic cells but is not
      required for cross-presentation in vivo.
AB  - Cross-presentation allows the processing of Ags from donor cells into the MHC
      class I presentation pathway of dendritic cells (DCs). This is important for the
      generation of cytotoxic T cell immunity and for induction of self tolerance.
      Apoptotic cells are reported to be efficient targets for cross-presentation, and
      in vitro studies using human DCs have implicated CD36 in their capture. In
      support of a role for CD36 in cross-presentation, we show that this molecule is
      differentially expressed by CD8(+) splenic DCs, which previously have been
      identified as responsible for cross-presentation in the mouse. Three different
      cross-presentation models were examined for their dependence on CD36. These
      included cross-priming to OVA-coated spleen cells and cross-tolerance to OVA
      transgenically expressed in the pancreatic islet beta cells under constitutive
      conditions or during beta cell destruction. In these models, CD36 knockout DCs
      were equivalent to wild-type DCs in their capacity to cross-present either
      foreign or self Ags, indicating that CD36 is not essential for cross-presentation
      of cellular Ags in vivo.

PMID- 12055216
TI  - Transendothelial migratory pathways of V delta 1+TCR gamma delta+ and V delta
      2+TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis
      patients: involvement of phosphatidylinositol 3 kinase and calcium calmodulin
      dependent kinase II.
AB  - We have previously reported that the Vdelta2(+)TCRgammadelta(+) T lymphocyte
      subset, expressing the NK receptor protein 1a (NKRP1a; CD161), is expanded in
      patients with relapsing-remitting multiple sclerosis and uses this molecule to
      migrate through endothelium. In this work, we show that Vdelta1(+) and Vdelta2(+)
      gammadelta T lymphocytes use distinct signal transduction pathways to accomplish
      this function. Indeed, we have found that Vdelta1(+) cells lack NKRP1a and
      selectively express the platelet endothelial cell adhesion molecule 1 (PECAM1;
      CD31), which drives transendothelial migration of this cell subset, at variance
      with Vdelta2(+) T cells, which are PECAM1 negative and use NKRP1a for
      transmigration. Interestingly, when Vdelta2(+) T cells were pretreated with two
      specific inhibitors of the calcium calmodulin-dependent kinase II KN62 and KN93,
      but not with the inactive compound KN92, the number of migrating cells and the
      rate of transmigration were significantly decreased. In turn, the
      phosphatidylinositol 3 kinase blockers wortmannin and LY294002 exerted a dose
      dependent inhibition of Vdelta1(+) cell migration. Finally, NKRP1a and PECAM1
      engagement led to activation of different signal transduction pathways: indeed,
      oligomerization of NKRP1a on Vdelta2(+) T cells activates calcium calmodulin
      dependent kinase II, while occupancy of PECAM1 on Vdelta1(+) cells triggers the
      phosphatidylinositol 3 kinase-dependent Akt/protein kinase Balpha activation.
      These findings suggest that subsets of gammadelta T lymphocytes may migrate to
      the site of lesion in multiple sclerosis using two different signaling pathways
      to extravasate.

PMID- 12055217
TI  - Differentially regulated expression and function of CD22 in activated B-1 and B-2
      lymphocytes.
AB  - CD22 is a B cell-restricted transmembrane protein that apparently controls signal
      transduction thresholds initiated through the B cell Ag receptor (BCR) in
      response to Ag. However, it is still poorly understood how the expression of CD22
      is regulated in B cells after their activation. Here we show that the expression
      levels of CD22 in conventional B-2 cells are markedly down-regulated after cross
      linking of BCR with anti-IgM mAb but are up-regulated after stimulation with LPS,
      anti-CD40 mAb, or IL-4. In contrast, treatment with anti-IgM mAb barely modulated
      the expression levels of CD22 in CD5(+) B-1 cells, consistent with a weak Ca(2+)
      response in anti-IgM-treated CD5(+) B-1 cells. Moreover, in CD22-deficient mice,
      anti-IgM treatment did not trigger enhanced Ca(2+) influx in CD5(+) B-1 cells,
      unlike CD22-deficient splenic B-2 cells, suggesting a relatively limited role of
      CD22 in BCR signaling in B-1 cells. In contrast, CD22 levels were markedly down
      regulated on wild-type B-1 cells in response to LPS or unmethylated CpG
      containing oligodeoxynucleotides. These data indicate that the expression and
      function of CD22 are differentially regulated in B-1 and conventional B-2 cells,
      which are apparently implicated in innate and adaptive immunity, respectively.

PMID- 12055218
TI  - Apoptosis mediated through CD45 is independent of its phosphatase activity and
      association with leukocyte phosphatase-associated phosphoprotein.
AB  - Besides the well-recognized role of CD45 as a major player in TCR signaling, we
      and others have demonstrated that cross-linking of CD45 with mAbs can induce cell
      death in T lymphocytes. To investigate the role of CD45 phosphatase activity in
      apoptosis induction, we expressed either wild-type or phosphatase-dead CD45
      molecules in a CD45-deficient BW5147 T cell line. We show here that the
      phosphatase activity of CD45 was not required for apoptosis triggering after
      cross-linking of the molecule. It is noteworthy that a revertant of the CD45
      negative BW5147 cell line, expressing a truncated form of CD45 lacking most of
      the cytoplasmic domain, was also susceptible to CD45-mediated death. Moreover, we
      also demonstrate that leukocyte phosphatase-associated phosphoprotein expression
      is totally dispensable for CD45-mediated apoptosis to occur. Taken together,
      these results strongly suggest a role for the extracellular and/or the
      transmembrane portion of CD45 in apoptosis signaling, which contrasts with the
      previously reported functions for CD45 in T lymphocytes.

PMID- 12055219
TI  - IL-2 and IL-12 alter NK cell responsiveness to IFN-gamma-inducible protein 10 by
      down-regulating CXCR3 expression.
AB  - Cytokine treatment of NK cells results in alterations in multiple cellular
      responses that include cytotoxicity, cytokine production, proliferation, and
      chemotaxis. To understand the molecular mechanisms underlying these responses,
      microarray analysis was performed and the resulting gene expression patterns were
      compared between unstimulated, IL-2, IL-2 plus IL-12, and IL-2 plus IL-18
      stimulated NK92 cells. RNase protection assays and RT-PCR confirmed microarray
      predictions for changes in mRNA expression for nine genes involved in cell cycle
      progression, signal transduction, transcriptional activation, and chemotaxis.
      Multiprobe RNase protection assay also detected changes in the expression of CCR2
      mRNA, a gene that was not imprinted on the microarray. We subsequently expanded
      our search for other chemokine receptor genes absent from the microarray and
      found an IL-2- and IL-12-dependent decrease in CXCR3 receptor mRNA expression in
      NK92 cells. A detailed analysis of CXCR3 expression in primary NK cells revealed
      that an IL-2 and an IL-12 together significantly decreased the CXCR3 receptor
      mRNA and receptor surface expression by 6 and 24 h of treatment, respectively.
      This decrease in receptor expression was associated with a significant reduction
      in chemotaxis in the presence of IFN-gamma-inducible protein-10. The decline in
      CXCR3 mRNA was due to transcriptional and posttranscriptional mechanisms as the
      addition of actinomycin D to IL-2- and IL-12-treated NK92 slightly altered the
      half-life of the CXCR3 mRNA. Collectively, these data suggest that IL-2 and IL-12
      directly affect NK cell migratory ability by rapid and direct down-regulation of
      chemokine receptor mRNA expression.

PMID- 12055220
TI  - Vaccination with tumor peptide in CpG adjuvant protects via IFN-gamma-dependent
      CD4 cell immunity.
AB  - The low frequency of tumor Ag-specific T cells in vivo has made it challenging to
      directly measure their clonal sizes and cytokine signatures. We used a new
      generation ELISPOT approach to study the constitutive immunogenicity of the RMA
      tumor in syngeneic B6 mice and adjuvant-guided immunity against an MHC class II
      restricted RMA peptide, H11.1. The RMA tumor was found to activate cells of the
      innate immune system and to induce a type 1 polarized, RMA-specific CD4 and CD8 T
      cell response. With clonal sizes approximately 10/10(6), the magnitude of this
      constitutively induced immune response did not suffice to control the tumor cell
      growth. In contrast, immunization with H11.1 peptide, using an immunostimulatory
      CpG oligonucleotide or CFA as adjuvant, engaged approximately 25- or
      approximately 10-fold higher clonal sizes of type 1 polarized CD4 cells,
      respectively. Therefore, the CpG oligonucleotide functioned as a stronger type 1
      adjuvant and, unlike CFA, elicited protective immunity. The protection was IFN
      gamma dependent, as it was not inducible in IFN-gamma knockout mice. Therefore,
      CpG adjuvant-guided induction of type 1 immunity against tumor Ags might be a
      promising subunit vaccination approach.

PMID- 12055221
TI  - CD4-Lck through TCR and in the absence of Vav exchange factor induces Bax
      increase and mitochondrial damage.
AB  - In the present study, we aimed to demonstrate that CD4 may represent a critical
      turning point that governs the apoptotic and survival programs in T cells,
      without modifying the physical association with the TCR-CD3 complex. To address
      this issue, we have explored the possibility that the activation of CD4 may
      transduce apoptotic signals unless signaling effectors neutralize them. Our data
      show that in Jurkat T cells CD4 engagement by Leu3a mAb results in a rapid and
      strong increase of Lck kinase activity, subsequent alterations of mitochondrial
      membrane potential, and apoptosis. Critical parameters are coassociation of
      CD4/Lck with TCR/CD3 and up-regulation of the proapoptotic protein Bax. Indeed,
      Leu3a-mediated Lck activation failed to induce apoptotic features in Jurkat cells
      either defective for TCR/CD3 or overexpressing the antiapoptotic protein Bcl-2.
      Furthermore, we demonstrate that Leu3a treatment of Jurkat cells overexpressing
      Vav results in the inhibition of mitochondrial damage and apoptosis; this rescue
      effect is accompanied with a significant decrease of Bax expression observed in
      apoptotic cells. Our evidence that the activation of Lck activates in T cells
      apoptotic pathways which are counteracted by Vav, a signaling molecule that
      cooperates with CD28 to boost TCR signals, suggests a novel role for
      costimulation in protecting T cells from CD4-mediated cell death.

PMID- 12055222
TI  - Murine Peyer's patches favor development of an IL-10-secreting, regulatory T cell
      population.
AB  - Peyer's patches (PP) are believed to be the principal sites for induction of
      tolerance to Ags from food and commensal flora, yet the phenotype of T cells
      activated within the PP is largely unexplored. We hypothesize that exposure to
      Ags within the PP promotes differentiation of T cells with immunoregulatory
      functions. Cytokine production and cell surface marker expression of murine PP
      mononuclear cells (MC) are compared with those from mesenteric lymph nodes and
      peripheral lymph nodes (PLN). In response to stimulation through the TCR/CD3
      complex, PP MC exhibit vigorous proliferation, modest production of IL-2, and
      significantly elevated synthesis of IL-10. Exogenous IL-12 enhances both IL-10
      and IFN-gamma secretion by activated PP MC. Cell surface marker analysis reveals
      that PP T cells consist of activated and memory subpopulations compared with the
      predominantly naive T cells identified in the PLN and mesenteric lymph nodes.
      Upon stimulation, only CD45RB(low)CD4(+) PP T cells produce IL-10, whereas
      secretion of IL-2, IL-4, and IFN-gamma was not detected. Furthermore, PP MC, but
      not PLN MC, stimulated through the TCR/CD3 complex suppress proliferation of
      purified PLN T cells in vitro, evidence for a regulatory function among PP
      lymphocytes. We conclude that PP favor differentiation of an IL-10-producing,
      regulatory CD45RB(low)CD4(+) T cell population and that inhibition of T cell
      proliferation by activated PP MC may reflect regulatory activity consistent with
      T regulatory cells.

PMID- 12055223
TI  - Early antigen-specific response by naive CD8 T cells is not altered with aging.
AB  - Both a dramatic decline in CD8 responses and a switch to memory T cell
      predominance occur with aging. The extent to which the loss of responsiveness is
      the consequence of the accumulation of more differentiated vs intrinsically
      defective T cells (or both) has been unclear. Using similar conditions of Ag
      stimulation, we have examined the responses generated by CD8(+) cells isolated
      from aged TCR transgenic mice. We found that the naive transgene(+) CD8(+) cells
      from aged 2C mice expressed activation markers, produced IL-2, proliferated, and
      differentiated into cytotoxic T cells as efficiently as their young counterparts.
      The extent of responsiveness and the level of the responses were comparable in
      both age groups regardless of the stimulatory conditions used, i.e., partial
      costimulation/adhesion molecule expression on APCs, or presentation of lower
      affinity peptide or diminished peptide concentrations. By day 4 after Ag
      stimulation, no significant age-related differences were observed in the number
      of effector cells generated nor in the levels of secreted IL-2 or IFN-gamma. Upon
      restimulation of effector cells, IL-2 secretion and to a lesser extent TNF-alpha
      expression, but not IFN-gamma secretion, were diminished with age. These findings
      suggest that age-associated alterations in naive CD8 cell function are not found
      after primary stimulation, but may become apparent upon restimulation.

PMID- 12055225
TI  - Lipopolysaccharide- and lipoteichoic acid-induced tolerance and cross-tolerance:
      distinct alterations in IL-1 receptor-associated kinase.
AB  - Human Toll-like receptor (TLR) 4 and TLR2 receptors recognize LPS or lipoteichoic
      acid (LTA), respectively. Prolonged exposure of human macrophages/monocytes to
      bacterial LPS induces a state of adaptation/tolerance to subsequent LPS
      challenge. Inflammatory gene expressions such as IL-1beta and TNF-alpha are
      selectively repressed, while certain anti-inflammatory genes such as secretory IL
      1R antagonist are still induced in LPS-adapted/tolerant cells. In this report, we
      demonstrate that LPS-tolerized human promonocytic THP-1 cells develop cross
      tolerance and no longer respond to LTA-induced IL-1beta/TNF-alpha production,
      indicating that disruption of common intracellular signaling is responsible for
      the decreased IL-1beta/TNF-alpha production. We observe that down-regulation of
      IL-1R-associated kinase (IRAK) protein level and kinase activity closely
      correlates with the development of cross-tolerance. IRAK protein levels and
      kinase activities in LPS-tolerized cells remain low and hyporesponsive to
      subsequent LPS or LTA challenges. We also demonstrate that THP-1 cells with
      prolonged LTA treatment develop LTA tolerance and do not express IL-1beta/TNF
      alpha upon further LTA challenge. Strikingly, cells tolerized with LTA are only
      refractory to subsequent LTA challenge and can still respond to LPS stimulation.
      Correspondingly, stimulation of TLR2 by LTA, although activating IRAK, does not
      cause IRAK degradation. IRAK from LTA-tolerized cells can be subsequently
      activated and degraded by further LPS challenge, but not LTA treatment. Our
      studies reveal that LTA-induced tolerance is distinct compared with that of LPS
      tolerance, and is likely due to disruption of unique TLR2 signaling components
      upstream of MyD88/IRAK.

PMID- 12055224
TI  - Catecholamines inhibit the antigen-presenting capability of epidermal Langerhans
      cells.
AB  - The sympathetic nervous system modulates immune function at a number of levels.
      Within the epidermis, APCs (Langerhans cells (LC)) are frequently anatomically
      associated with peripheral nerves. Furthermore, some neuropeptides have been
      shown to regulate LC Ag-presenting function. We explored the expression of
      adrenergic receptors (AR) in murine LC and assessed their functional role on Ag
      presentation and modulation of cutaneous immune responses. Both purified LC and
      the LC-like cell lines XS52-4D and XS106 expressed mRNA for the ARs alpha(1A) and
      beta(2). XS106 cells and purified LC also expressed beta(1)-AR mRNA. Treatment of
      murine epidermal cell preparations with epinephrine (EPI) or norepinephrine
      inhibited Ag presentation in vitro. Furthermore, pretreatment of epidermal cells
      with EPI or norepinephrine in vitro suppressed the ability of these cells to
      present Ag for elicitation of delayed-type hypersensitivity in previously
      immunized mice. This effect was blocked by use of the beta(2)-adrenergic
      antagonist ICI 118,551 but not by the alpha-antagonist phentolamine. Local
      intradermal injection of EPI inhibited the induction of contact hypersensitivity
      to epicutaneously administered haptens. Surprisingly, injection of EPI at a
      distant site also suppressed induction of contact hypersensitivity. Thus,
      catecholamines may have both local and systemic effects. We conclude that
      specific ARs are expressed on LC and that signaling through these receptors can
      decrease epidermal immune reactions.

PMID- 12055226
TI  - The absence of Itk inhibits positive selection without changing lineage
      commitment.
AB  - The Tec family tyrosine kinase Itk is critical for efficient signaling downstream
      of the TCR. Biochemically, Itk is directly phosphorylated and activated by Lck.
      Subsequently, Itk activates phospholipase C-gamma1, leading to calcium
      mobilization and extracellular signal-regulated kinase/mitogen-activated protein
      kinase activation. These observations suggested that Itk might play an important
      role in positive selection and CD4/CD8 lineage commitment during T cell
      development in the thymus. To test this, we crossed Itk-deficient mice to three
      lines of TCR transgenics and analyzed progeny on three different MHC backgrounds.
      Analysis of these mice revealed that fewer TCR transgenic T cells develop in the
      absence of Itk. In addition, examination of multiple T cell development markers
      indicates that multiple stages of positive selection are affected by the absence
      of Itk, but the T cells that do develop appear normal. In contrast to the defects
      in positive selection, CD4/CD8 lineage commitment seems to be intact in all the
      TCR transgenic itk(-/-) lines tested. Overall, these data indicate that altering
      TCR signals by the removal of Itk does not affect the appropriate differentiation
      of thymocytes based on their MHC specificity, but does impact the efficiency with
      which thymocytes complete their maturation process.

PMID- 12055227
TI  - Down-regulation of monocyte apoptosis by phagocytosis of platelets: involvement
      of a caspase-9, caspase-3, and heat shock protein 70-dependent pathway.
AB  - Monocytes interact and cross-talk with platelets in many settings including
      inflammation, hemostasis, or vascular disorders. During inflammatory diseases,
      there is a rapid targeting of monocytes and platelets to points of inflammation
      and endothelial injury, where they lie side-by-side. In this in vitro study, we
      investigated different interactions between monocytes and platelets and
      elucidated whether platelets might affect monocyte apoptosis. Freshly isolated
      human monocytes were rendered apoptotic by serum deprivation or CD95 ligation and
      cocultured with platelets. Monocyte apoptosis was determined by flow cytometry,
      TUNEL staining, DNA electrophoresis, and transmission electron microscopy
      imaging. We could show that monocyte apoptosis was highly suppressed when
      platelets were added to the cultures. Transmission electron microscopy depicted
      that monocytes completely ingested thrombocytes by phagocytosis. Blocking
      thrombocyte uptake by the phagocytosis inhibitor cytochalasin D abrogated the
      enhanced monocyte survival and led to high apoptosis levels. Monocyte survival
      was paralleled by down-regulation of caspase-9 and -3 and up-regulation of heat
      shock protein 70 during uptake of platelets. Platelet supernatants and contents
      of platelet granules were ineffective in altering monocyte senescence. Also,
      ingestion of latex beads or zymosan by monocytes was ineffective to mimic
      platelet-dependent rescue from apoptosis. In conclusion, this study shows that
      platelets can suppress apoptosis of monocytes by a specific phagocytosis
      dependent process with further consequences for atherosclerotic or inflammatory
      conditions.

PMID- 12055228
TI  - Regulation of diabetes development by regulatory T cells in pancreatic islet
      antigen-specific TCR transgenic nonobese diabetic mice.
AB  - Nonobese diabetic (NOD) mice carrying a transgenic TCR from an islet Ag-specific
      CD4 T cell clone, BDC2.5, do not develop diabetes. In contrast, the same
      transgenic NOD mice on the SCID background develop diabetes within 4 wk after
      birth. Using a newly developed mAb specific for the BDC2.5 TCR, we examined the
      interaction between diabetogenic T cells and regulatory T cells in NOD.BDC
      transgenic mice. CD4 T cells from NOD.BDC mice, expressing high levels of the
      clonotype, transfer diabetes to NOD.SCID recipients. In contrast, CD4 T cells
      expressing low levels due to the expression of both transgenic and endogenous TCR
      alpha-chains inhibit diabetes transfer. The clonotype-low CD4 T cells appear late
      in the ontogeny in the thymus and peripheral lymphoid organs, coinciding with
      resistance to cyclophosphamide-induced diabetes. These results demonstrate that
      diabetic processes in NOD.BDC mice are regulated by a balance between
      diabetogenic T cells and regulatory T cells. In the absence of specific
      manipulation, regulatory T cell function seems to be dominant and mice remain
      diabetes free. Understanding of mechanisms by which regulatory T cells inhibit
      diabetogenic processes would provide means to prevent diabetes development in
      high-risk human populations.

PMID- 12055229
TI  - Role of IFN-gamma in Th1 differentiation: IFN-gamma regulates IL-18R alpha
      expression by preventing the negative effects of IL-4 and by inducing/maintaining
      IL-12 receptor beta 2 expression.
AB  - Two key events occur during the differentiation of IFN-gamma-secreting Th1 cells:
      up-regulation of IL-12Rbeta2 and IL-12-driven up-regulation of IL-18Ralpha. We
      previously demonstrated that IL-12-driven up-regulation of IL-18Ralpha expression
      is severely impaired in IFN-gamma(-/-) mice. However, it was unclear from these
      studies how IFN-gamma influenced IL-18Ralpha since IFN-gamma alone had no direct
      effect on IL-18Ralpha expression. In the absence of IL-4, IL-12-dependent up
      regulation of IL-18Ralpha/IL-12Rbeta2 was independent of IFN-gamma. However, in
      the presence of IL-4, IFN-gamma functions to limit the negative effects of IL-4
      on both IL-18Ralpha and IL-12Rbeta2. Neutralization of IL-4 restored IL-12-driven
      up-regulation of IL-18Ralpha/IL-12Rbeta2 in an IFN-gamma-independent fashion. In
      the absence of both IL-12 and IL-4, IFN-gamma up-regulates IL-12beta2 expression
      and primes IFN-gamma-producing Th1 cells. When T cells were primed in the
      presence of IL-4, no correlation was found between the levels of expression of
      the IL-18Ralpha or the IL-12Rbeta2 and the capacity of these cells to produce IFN
      gamma, suggesting that IL-4 may also negatively affect IL-12-mediated signal
      transduction and thus Th1 differentiation. These data clarify the role of IFN
      gamma in regulation of IL-18Ralpha/IL-12Rbeta2 during both IL-12-dependent and IL
      12-independent Th1 differentiation.

PMID- 12055230
TI  - Dual functions of fractalkine/CX3C ligand 1 in trafficking of perforin+/granzyme
      B+ cytotoxic effector lymphocytes that are defined by CX3CR1 expression.
AB  - Fractalkine/CX3C ligand 1 and its receptor CX3CR1 are known to mediate both cell
      adhesion and cell migration. Here we show that CX3CR1 defines peripheral blood
      cytotoxic effector lymphocytes commonly armed with intracellular perforin and
      granzyme B, which include NK cells, gammadelta T cells, and terminally
      differentiated CD8(+) T cells. In addition, soluble fractalkine preferentially
      induced migration of cytotoxic effector lymphocytes. Furthermore, interaction of
      cytotoxic effector lymphocytes with membrane-bound fractalkine promoted
      subsequent migration to the secondary chemokines, such as macrophage inflammatory
      protein-1beta/CC ligand 4 or IL-8/CXC ligand 8. Thus, fractalkine expressed on
      inflamed endothelium may function as a vascular regulator for cytotoxic effector
      lymphocytes, regardless of their lineage and mode of target cell recognition,
      through its ability to capture them from blood flow and to promote their
      emigration in response to other chemokines.

PMID- 12055231
TI  - Corticosteroids prevent generation of CD34+-derived dermal dendritic cells but do
      not inhibit Langerhans cell development.
AB  - Corticosteroids (CS) have been shown to exert strong inhibitory effects on
      dendritic cell (DC) differentiation and function. Those studies were mostly
      performed with monocyte-derived DC, which represents only one subpopulation from
      the wide variety of DC types. In the present study the effects of the CS
      dexamethasone and prednisolone were investigated on the differentiation of
      CD34(+) hemopoietic progenitor cells into 1) Langerhans cells (LC), which
      differentiate directly into CD1a(+) DC; and 2) dermal/interstitial DC, which
      differentiate via a CD14(+)CD1a(-) phenotype into CD14(-)CD1a(+) DC. CS present
      during the entire 11-day culture period, resulting in fully differentiated
      CD1a(+) DC, increased the percentage of langerin(+) DC within the CD1a(+)
      population. In line with these data, CS treatment during the first 6 days of
      differentiation reduced the development of CD14(+) dermal DC precursors and
      thereby seemed to support the generation of CD1a(+) LC precursors. Addition of CS
      from day 6 onward specifically blocked the development of CD1a(+) dermal DC by
      both inhibition of spontaneous and IL-4-induced differentiation of CD14(+) DC
      precursors into CD1a(+) DC as well as induction of apoptosis in CD14(+) DC
      precursors. Apoptosis was not found in CD14(+) macrophage precursors derived from
      the same CD34(+) progenitors. The development and function of LC were not
      affected by CS, as demonstrated by a normal T cell stimulatory capacity and IL-12
      production. These data demonstrate that CS interfere with the normal development
      of DC from CD34(+) progenitors by specific induction of apoptosis in precursors
      of dermal/interstitial DC. In view of the different functional capacities of
      dermal/interstitial DC and Langerhans cells, this might affect the overall
      cellular immune response.

PMID- 12055232
TI  - A decaepitope polypeptide primes for multiple CD8+ IFN-gamma and Th lymphocyte
      responses: evaluation of multiepitope polypeptides as a mode for vaccine
      delivery.
AB  - Proteins are generally regarded as ineffective immunogens for CTL responses. We
      synthesized a 100-mer decaepitope polypeptide and tested its capacity to induce
      multiple CD8(+) IFN-gamma and Th lymphocyte (HTL) responses in HLA transgenic
      mice. Following a single immunization in the absence of adjuvant, significant IFN
      gamma in vitro recall responses were detected for all epitopes included in the
      construct (six A2.1-, three A11-restricted CTL epitopes, and one universal HTL
      epitope). Immunization with truncated forms of the decaepitope polypeptide was
      used to demonstrate that optimal immunogenicity was associated with a size of at
      least 30-40 residues (3-4 epitopes). Solubility analyses of the truncated
      constructs were used to identify a correlation between immunogenicity for IFN
      gamma responses and the propensity of these constructs to form particulate
      aggregates. Although the decaepitope polypeptide and a pool of epitopes
      emulsified in IFA elicited similar levels of CD8(+) responses using fresh
      splenocytes, we found that the decaepitope polypeptide more effectively primed
      for in vitro recall CD8(+) T cell responses. Finally, immunogenicity comparisons
      were also made between the decaepitope polypeptide and a corresponding gene
      encoding the same polypeptide delivered by naked DNA immunization. Although naked
      DNA immunization induced somewhat greater direct ex vivo and in vitro recall
      responses 2 wk after a single immunization, only the polypeptide induced
      significant in vitro recall responses 6 wk following the priming immunization.
      These studies support further evaluation of multiepitope polypeptide vaccines for
      induction of CD8(+) IFN-gamma and HTL responses.

PMID- 12055233
TI  - A novel role for IL-3: human monocytes cultured in the presence of IL-3 and IL-4
      differentiate into dendritic cells that produce less IL-12 and shift Th cell
      responses toward a Th2 cytokine pattern.
AB  - Dendritic cells (DC) derived from plasmacytoid precursors depend on IL-3 for
      survival and proliferation in culture, and they induce preferentially Th2
      responses. Monocytes express not only GM-CSF receptors, but also IL-3Rs.
      Therefore, we examined whether IL-3 had an effect on the functional plasticity of
      human monocyte-derived DC generated in a cell culture system that is widely used
      in immunotherapy. DC were generated with IL-3 (instead of GM-CSF) and IL-4.
      Yields, maturation, phenotype (surface markers and Toll-like receptors),
      morphology, and immunostimulatory capacity were similar. Only CD1a was
      differentially expressed, being absent on IL-3-treated DC. In response to CD40
      ligation DC generated in the presence of IL-3 secreted significantly less IL-12
      p70 and more IL-10 compared with DC grown with GM-CSF. Coculture of naive
      allogeneic CD4(+) T cells with DC generated in the presence of IL-3 induced T
      cells to produce significantly more IL-5 and IL-4 and less IFN-gamma compared
      with stimulation with DC generated with GM-CSF. These data extend the evidence
      that different cytokine environments during differentiation of monocyte-derived
      DC can modify their Th cell-inducing properties. A hitherto unrecognized effect
      of IL-3 on DC was defined, namely suppression of IL-12 secretion and a resulting
      shift from Th1 toward Th2.

PMID- 12055234
TI  - KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential.
AB  - KIR2DL4 (CD158d) is an unusual member of the killer cell Ig-like receptor family
      expressed in all NK cells and some T cells. KIR2DL4 activates the cytotoxicity of
      NK cells, despite the presence of an immunoreceptor tyrosine-based inhibition
      motif (ITIM) in its cytoplasmic tail. The role of this ITIM on the activating
      function of KIR2DL4, and whether it can provide inhibitory signals, is not known.
      Mutated forms of KIR2DL4 were engineered that lacked either the tyrosine in the
      ITIM or an arginine-tyrosine motif in the transmembrane region that is required
      for the activation signal. The activity of the mutated KIR2DL4 molecules was
      tested in a redirected lysis assay. The ITIM was not necessary for activation of
      lysis by KIR2DL4. The activation signal of KIR2DL4 was sensitive to inhibition by
      another ITIM-containing receptor. The activation-deficient mutant of KIR2DL4
      inhibited the signal delivered by the activating receptor CD16. In pull-down
      experiments with GST fusion proteins, the tyrosine-phosphorylated cytoplasmic
      tail of KIR2DL4 bound the Src homology 2-containing phosphatases 1 and 2, as did
      the tail of the inhibitory receptor KIR2DL1. Therefore, KIR2DL4 has inhibitory
      potential in addition to its activating function.

PMID- 12055235
TI  - Overexpression of insulin receptor substrate-1, but not insulin receptor
      substrate-2, protects a T cell hybridoma from activation-induced cell death.
AB  - The insulin receptor substrate (IRS) family of signaling molecules is expressed
      in lymphocytes, although their functions in these cells is largely unknown. To
      investigate the role of IRS in the protection of T cells from activation-induced
      cell death (AICD), we transfected the T cell hybridoma A1.1, which is IL-4
      responsive but lacks expression of IRS family members with cDNA encoding IRS1 or
      IRS2. Stimulation of these clones with immobilized anti-CD3-induced expression of
      CD69 to the same level as the parental A1.1 cells. However, the A1.1 IRS1
      expressing cells were markedly resistant to AICD, while the A1.1 IRS2-expressing
      cells were not. Inhibition of phosphatidylinositol 3'-kinase in the A1.1 IRS1
      expressing cells did not abrogate their resistance to AICD. Fas mRNA was induced
      similarly by anti-CD3 in A1.1, A1.1 IRS1-expressing, and A1.1 IRS2-expressing
      cells. However, induction of Fas ligand (FasL) mRNA and functional FasL protein
      was delayed and decreased in IRS1-expressing cells, but not in IRS2-expressing
      cells. The induction of transcription from a 500-bp FasL promoter and a minimal
      16-mer early growth response element linked to luciferase was also impaired in
      the IRS1-expressing cells. These results suggest that overexpression of IRS1, but
      not IRS2, protects A1.1 cells from AICD by diminishing FasL transcription through
      a pathway that is independent of the tyrosine phosphorylation of IRS1 and
      phosphatidylinositol 3'-kinase activity.

PMID- 12055236
TI  - IFN-stimulated gene 15 is synergistically activated through interactions between
      the myelocyte/lymphocyte-specific transcription factors, PU.1, IFN regulatory
      factor-8/IFN consensus sequence binding protein, and IFN regulatory factor-4:
      characterization of a new subtype of IFN-stimulated response element.
AB  - Type I IFNs cause the induction of a subset of genes termed IFN-stimulated genes
      (ISGs), which harbor a specific DNA element, IFN-stimulated response element
      (ISRE). This ISRE confers the responsiveness to the IFN signal through the
      binding of a family of transcription factors designated IFN regulatory factors
      (IRFs). Some IRFs can bind to the DNA alone, such as IRF-1, which elicits
      transcriptional activation, or IRF-2, which leads to transcriptional repression.
      In addition, these factors associate with IRF-8/IFN consensus sequence binding
      protein (ICSBP), an immune cell-restricted IRF, and the assembled heterocomplexes
      lead to synergistic repression of ISRE elements. ISG15 is a prototype ISG that
      contains a well-characterized ISRE. Here we show that PU.1, an ETS member
      essential for myeloid/lymphoid cell differentiation, forms heterocomplexes with
      the immune-restricted IRFs, IRF-8?/ICSBP and IRF-4, which lead to transcriptional
      activation of ISG15. These data allowed the characterization of a subset of ISREs
      designated ETS/IRF response element (EIRE), which are differentially regulated in
      immune cells. EIREs are unique in their ability to recruit different factors to
      an assembled enhanceosomes. In nonimmune cells the factors will mainly include
      IRF members, while cell type-restricted factors, such as PU.1, IRF-8?/ICSBP, and
      IRF-4, will be recruited in immune cells. IRF heterocomplex formation leads to
      transcriptional repression, and conversely, PU.1/IRFs heterocomplex formation
      leads to transcriptional activation. The fact that IRF-8?/ICSBP is an IFN-gamma
      induced factor explains why some of the EIREs are also induced by type II IFN.
      Our results lay the molecular basis for the unique regulation of ISGs, harboring
      EIRE, in immune cells.

PMID- 12055237
TI  - Prostaglandin D2 and its metabolites induce caspase-dependent granulocyte
      apoptosis that is mediated via inhibition of I kappa B alpha degradation using a
      peroxisome proliferator-activated receptor-gamma-independent mechanism.
AB  - Many inflammatory mediators retard granulocyte apoptosis. Most natural PGs
      studied herein (e.g., PGE(2), PGA(2), PGA(1), PGF(2 alpha)) either delayed
      apoptosis or had no effect, whereas PGD(2) and its metabolite PGJ(2) selectively
      induced eosinophil, but not neutrophil apoptosis. This novel proapoptotic effect
      does not appear to be mediated via classical PG receptor ligation or by elevation
      of intracellular cAMP or Ca(2+). Intriguingly, the sequential metabolites
      Delta(12)PGJ(2) and 15-deoxy-Delta(12,) Delta(14)-PGJ(2) (15dPGJ(2)) induced
      caspase-dependent apoptosis in both granulocytes, an effect that did not involve
      de novo protein synthesis. Despite the fact that Delta(12)PGJ(2) and 15dPGJ(2)
      are peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activators,
      apoptosis was not mimicked by synthetic PPAR-gamma and PPAR-alpha ligands or
      blocked by an irreversible PPAR-gamma antagonist. Furthermore, Delta(12)PGJ(2)
      and 15dPGJ(2) inhibited LPS-induced I kappa B alpha degradation and subsequent
      inhibition of neutrophil apoptosis, suggesting that apoptosis is mediated via
      PPAR-gamma-independent inhibition of NF-kappa B activation. In addition, we show
      that TNF-alpha-mediated loss of cytoplasmic I kappa B alpha in eosinophils is
      inhibited by 15dPGJ(2) in a concentration-dependent manner. The selective
      induction of eosinophil apoptosis by PGD(2) and PGJ(2) may help define novel
      therapeutic pathways in diseases in which it would be desirable to specifically
      remove eosinophils but retain neutrophils for antibacterial host defense. The
      powerful proapoptotic effects of Delta(12)PGJ(2) and 15dPGJ(2) in both
      granulocyte types suggest that these natural products control the longevity of
      key inflammatory cells and may be relevant to understanding the control and
      resolution of inflammation.

PMID- 12055238
TI  - Expression of functional CCR and CXCR chemokine receptors in podocytes.
AB  - Chemokines and their receptors play an important role in the pathogenesis of
      acute and chronic glomerular inflammation. However, their expression pattern and
      function in glomerular podocytes, the primary target cells in a variety of
      glomerulopathies, have not been investigated as of yet. Using RT-PCR, we now
      demonstrate the expression of CCR4, CCR8, CCR9, CCR10, CXCR1, CXCR3, CXCR4, and
      CXCR5 in cultured human podocytes. Stimulation of these receptors induced a
      concentration-dependent biphasic increase of the free cytosolic calcium
      concentration in podocytes in culture. In addition, we demonstrate that podocytes
      release IL-8 in the presence of FCS and that IL-8 down-regulates cell surface
      CXCR1. Chemokine stimulation of the detected CCRs and CXCRs increased activity of
      NADPH-oxidase, the primary source of superoxide anions in podocytes.
      Immunohistochemistry studies revealed only diffuse and weak CXCR expression in
      healthy human glomerula. In contrast, in membranous nephropathy, a characteristic
      podocyte disorder, the expression of CXCR1, CXCR3, and CXCR5 is up-regulated in
      podocytes. In conclusion, podocytes in culture and podocytes in human kidney
      sections express a set of chemokine receptors. The release of oxygen radicals
      that accompanies the activation of CCRs and CXCRs may contribute to podocyte
      injury and the development of proteinuria during membranous nephropathy.

PMID- 12055239
TI  - The immunodominant, Ld-restricted T cell response to hepatitis B surface antigen
      (HBsAg) efficiently suppresses T cell priming to multiple Dd-, Kd-, and Kb
      restricted HBsAg epitopes.
AB  - MHC-I-restricted CTL responses of H-2(d) (L(d+) or L(d-)) and F(1) H-2(dxb) mice
      to hepatitis B surface Ag (HBsAg) are primed by either DNA vaccines or HBsAg
      particles. The D(d)/S(201-209) and K(d)/S(199-208) epitopes are generated by
      processing endogenous HBsAg; the K(b)/S(208-215) epitope is generated by
      processing exogenous HBsAg; and the L(d)/S(28-39) epitope is generated by
      exogenous as well as endogenous processing of HBsAg. DNA vaccination primed high
      numbers of CTL specific for the L(d)/S(28-39) HBsAg epitope, low numbers of CTL
      specific for the D(d)/S(201-209) or K(d)/S(199-208) HBsAg epitopes in BALB/c
      mice, and high numbers of D(d)/S(201-209)- and K(d)/S(199-208)-specific CTL in
      congenic H-2(d)/L(d-) dm2 mice. In F(1)(dxb) mice, the K(d)-, D(d)-, and K(b)
      restricted CTL responses to HBsAg were strikingly suppressed in the presence but
      efficiently elicited in the absence of L(d)/S(28-39)-specific CTL. Once primed,
      the K(d)- and D(d)-restricted CTL responses to HBsAg were resistant to
      suppression by immunodominant L(d)/S(28-39)-specific CTL. The L(d)-restricted
      immunodominant CTL reactivity to HBsAg can thus suppress priming to multiple
      alternative epitopes of HBsAg, independent of the processing pathway that
      generates the epitope, of the background of the mouse strain used, and of the
      presence/absence of different allelic variants of the K and D MHC class I
      molecules.

PMID- 12055240
TI  - An abortive ligand-induced activation of CCR1-mediated downstream signaling event
      and a deficiency of CCR5 expression are associated with the hyporesponsiveness of
      human naive CD4+ T cells to CCL3 and CCL5.
AB  - Human memory CD4(+) T cells respond better to inflammatory CCLs/CC chemokines,
      CCL3 and CCL5, than naive CD4(+) T cells. We analyzed the regulatory mechanism
      underlying this difference. Memory and naive CD4(+) T cells expressed similarly
      high levels of CCR1; however, CCR5 was only expressed in memory CD4(+) T cells at
      low levels. Experiments using mAbs to block chemokine receptors revealed that
      CCR1 functioned as a major receptor for the binding of CCL5 in memory and naive
      CD4(+) T cells as well as the ligand-induced chemotaxis in memory CD4(+) T cells.
      Stimulation of memory CD4(+) T cells with CCL5 activated protein tyrosine kinase
      dependent cascades, which were significantly blocked by anti-CCR1 mAb, whereas
      this stimulation failed to induce these events in naive CD4(+) T cells.
      Intracellular expressions of regulator of G protein signaling 3 and 4 were only
      detected in naive CD4(+) T cells. Pretreatment of cell membrane fractions from
      memory and naive CD4(+) T cells with GTP-gamma S inhibited CCL5 binding,
      indicating the involvement of G proteins in the interaction of CCL5 and its
      receptor(s). In contrast, CCL5 enhanced the GTP binding to G(i alpha) and G(q
      alpha) in memory CD4(+) T cells, but not in naive CD4(+) T cells. Thus, a failure
      of the ligand-induced activation of CCR1-mediated downstream signaling event as
      well as a deficiency of CCR5 expression may be involved in the hyporesponsiveness
      of naive CD4(+) T cells to CCL3 and CCL5.

PMID- 12055241
TI  - Peptide mimotopes of pneumococcal capsular polysaccharide of 6B serotype: a
      peptide mimotope can bind to two unrelated antibodies.
AB  - Two groups of bacteriophage clones displaying the antigenic properties of
      serotype 6B pneumococcal capsular polysaccharide (PS) were obtained from
      different phage libraries expressing random heptameric peptides. One group,
      biopanned with a mouse mAb (Hyp6BM1), is comprised of 17 phage clones expressing
      10 unique sequences of linear peptides. The other group, selected with another
      mAb (Hyp6BM8), contained six clones, all of which expressed the identical
      circular peptide. Phage clones expressing the linear peptides (e.g., PhaM1L3)
      bound only to Hyp6BM1, but not other 6B PS-specific mAb, and their binding could
      be inhibited with pneumococcal capsular type 6B PS only. In contrast, a phage
      clone expressing the circular peptide (PhaM8C1) cross-reacted with several other
      6B PS-specific mAbs, and their binding could be inhibited with pneumococcal
      capsular PS of 6A and 6B serotypes. Two short peptides, PepM1L3 and PepM8C1,
      reflecting the peptide inserts of the corresponding phage clones, could inhibit
      the binding of the two clones to their respective mAb. Interestingly, the peptide
      insert in PhaM8C1 was identical to that in PhaB3C4, a previously reported
      mimotope of alpha(2-->8) polysialic acid, Neisseria meningitidis group B PS.
      Indeed, PhaM8C1 bound to HmenB3 (a meningococcal Ab), and their association could
      be inhibited with alpha(2-8) polysialic acid, but not with 6B PS. Conversely,
      alpha(2-8) polysialic acid could not inhibit the binding of PhaM8C1 to Hyp6BM8.
      The two-dimensional nuclear magnetic resonance studies indicate that PepM8C1
      peptide can assume several conformations in solution. The ability of this peptide
      to assume multiple conformations might account for its ability to mimic more than
      one Ag type.

PMID- 12055242
TI  - Functional analysis of the human complement receptor 2 (CR2/CD21) promoter:
      characterization of basal transcriptional mechanisms.
AB  - Human complement receptor (CR) type 2 (CR2/CD21) is a 145-kDa membrane protein
      encoded within the regulators of complement activation gene cluster localized on
      human chromosome 1q32. Understanding the mechanisms that regulate CR2 expression
      is important because CR2 is expressed during specific stages of B cell
      development, and several lines of evidence suggest a role for altered CR2
      function or expression in a number of autoimmune diseases. Additionally, even
      modest changes in CR2 expression are likely to affect relative B cell responses.
      In this study we have delineated the transcriptional requirements of the human
      CR2 gene. We have studied the human CR2 proximal promoter and identified sites
      important for controlling the level of transcription in CR2-expressing cells. We
      have determined that four functionally relevant sites lie within very close
      proximity to the transcriptional initiation site. These sites bind the
      transcription factors USF1, an AP-2-like transcription factor, and Sp1.

PMID- 12055243
TI  - VpreB1/VpreB2/lambda 5 triple-deficient mice show impaired B cell development but
      functional allelic exclusion of the IgH locus.
AB  - At the precursor B cell stage during bone marrow B cell development, Ig muH chain
      associates with surrogate L (SL) chain, which is encoded by the three genes
      VpreB1, VpreB2, and lambda 5, to form the pre-B cell receptor (pre-BCR). Surface
      expression of the pre-BCR is believed to signal both proliferation and allelic
      exclusion of the IgH locus. Mice which lack either VpreB1/VpreB2 or lambda 5 show
      a lack of precursor B cell expansion but normal IgH allelic exclusion. This would
      suggest that one of either lambda 5 or VpreB can make a pre-BCR-like complex
      which is still able to signal allelic exclusion but not proliferation. To
      investigate this, we established mice lacking all components of the SL chain.
      These mice showed severely impaired B cell development which was similar to that
      previously found in mice lacking either lambda 5 or VpreB1/VpreB2. Surprisingly,
      the IgH locus was still allelically excluded and thus the SL chain appears not to
      be involved in allelic exclusion.

PMID- 12055244
TI  - Characterization of mouse and human B7-H3 genes.
AB  - T cell activation and immune function are regulated by costimulatory molecules of
      the B7 superfamily. Human B7-H3 is a recent addition to this family and has been
      shown to mediate T cell proliferation and IFN-gamma production. In this work we
      describe the identification of the mouse B7-H3 homolog, which is ubiquitously
      expressed in a variety of tissues. Activated CD4 and CD8 T cells express a
      putative receptor that can be recognized by soluble mouse B7-H3-Ig molecules.
      While the mouse B7-H3 gene was found to contain a single copy, we discovered a
      novel isoform of human B7-H3 (named as B7-H3b hereafter) with four Ig-like
      domains that results from gene duplication and differential splicing. B7-H3b is
      the major isoform expressed in several tissues. This structural information
      suggests a genetic variation of the B7-H3 gene in mammalian species.

PMID- 12055246
TI  - Analysis of IgE antibodies from a patient with atopic dermatitis: biased V gene
      usage and evidence for polyreactive IgE heavy chain complementarity-determining
      region 3.
AB  - To better understand V gene usage, specificity, and clonal origins of IgE Abs in
      allergic reactions, we have constructed a combinatorial Ab library from the mRNA
      of an adult patient with atopic dermatitis. Sequence analysis of random clones
      revealed that 33% of clones used the IGHV6-1 H chain V gene segment, the only
      member of the V(H)6 gene family. IGHV6-1 is rarely used in the expressed adult
      repertoire; however, it is associated with fetal derived Abs. Features of the
      V(H)6 rearrangements included short complementarity-determining region 3,
      frequent use of IGHD7-27 D gene, and little nucleotide addition at the D-J
      junction. There was also a low level of mutation compared with V(H)1, V(H)3, and
      V(H)4 rearrangements. The library was expressed as phage-Fab fusions, and
      specific phage selected by panning on the egg allergen ovomucoid. Upon expression
      as soluble IgE Fabs, 12 clones demonstrated binding to ovomucoid, skim milk, and
      BSA by ELISA. Nucleotide sequencing demonstrated that the IGHV6-1 V gene segment
      encoded each of the 12 multiply reactive IgE Fabs. A cyclic peptide was designed
      from the complementarity-determining region 3 of several of these clones. The
      cyclic peptide bound both self and nonself Ags, including ovomucoid, human IgG,
      tetanus toxoid, and human and bovine von Willebrand factor. These results suggest
      that some IgE Abs may bind more than one Ag, which would have important
      implications for understanding the multiple sensitivities seen in conditions such
      as atopic dermatitis.

PMID- 12055245
TI  - Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited
      on cells.
AB  - C4b and C3b deposited on host cells undergo limited proteolytic cleavage by
      regulatory proteins. Membrane cofactor protein (MCP; CD46), factor H, and C4b
      binding protein mediate this reaction, known as cofactor activity, that also
      requires the plasma serine protease factor I. To explore the roles of the fluid
      phase regulators vs those expressed on host cells, a model system was used
      examining complement fragments deposited on cells transfected with human MCP as
      assessed by FACS and Western blotting. Following incubation with Ab and
      complement on MCP(+) cells, C4b was progressively cleaved over the first hour to
      C4d and C4c. There was no detectable cleavage of C4b on MCP(-) cells, indicating
      that MCP (and not C4BP in the serum) primarily mediates this cofactor activity.
      C3b deposition was not blocked on MCP(+) cells because classical pathway
      activation occurred before substantial C4b cleavage. Cleavage, though, of
      deposited C3b was rapid (<5 min) and iC3b was the dominant fragment on MCP(-) and
      MCP(+) cells. Studies using a function-blocking mAb further established factor H
      as the responsible cofactor. If the level of Ab sensitization was reduced 8-fold
      or if Mg(2+)-EGTA was used to block the classical pathway, MCP efficiently
      inhibited C3b deposition mediated by the alternative pathway. Thus, for the
      classical pathway, MCP is the cofactor for C4b cleavage and factor H for C3b
      cleavage. However, if the alternative pathway mediates C3b deposition, then MCP's
      cofactor activity is sufficient to restrict complement activation.

PMID- 12055247
TI  - B cell receptor- and beta 2-adrenergic receptor-induced regulation of B7-2 (CD86)
      expression in B cells.
AB  - The costimulatory molecule B7-2 (CD86) is expressed on the surface of APCs,
      including B cells. Considering the importance of B7-2 in regulating both T and B
      cell function, it may be important to understand the regulatory mechanisms
      governing its expression. We report in this study that stimulation of the B cell
      receptor (BCR) and/or a neurotransmitter receptor, the beta(2)-adrenergic
      receptor (beta(2)AR), may cooperate to regulate B cell-associated B7-2 expression
      in vitro and in vivo. beta(2)AR stimulation further enhanced the level of BCR
      induced B7-2 expression in B cells potentially via protein tyrosine kinase-,
      protein kinase A-, protein kinase C-, and mitogen-activated protein kinase
      dependent mechanisms. Importantly, BCR and/or beta(2)AR stimulation, but not
      histone hyperacetylation and DNA hypomethylation alone, increased B cell
      associated B7-2 expression by increasing B7-2 mRNA stability, NF-kappa B nuclear
      binding, and NF-kappa B-dependent gene transcription. Thus, this study provides
      additional insight into the signaling intermediates and molecular mechanisms by
      which stimulation of the BCR and beta(2)AR may regulate B cell-associated B7-2
      expression.

PMID- 12055248
TI  - A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan
      speaking Native Americans.
AB  - Athabascan SCID (SCIDA) is an autosomal recessive disorder found among Athabascan
      speaking Native Americans and is manifested by the absence of both T and B cells
      (T(-)B(-)NK(+) SCID). We previously mapped the SCIDA gene to a 6.5-cM interval on
      chromosome 10p. SCIDA fibroblasts were found to have defective coding joint and
      reduced, but precise signal joint formation during V(D)J recombination. After
      excluding potential candidate genes, we conducted a combined positional candidate
      and positional cloning approach leading to the identification of nine novel
      transcripts in the refined SCIDA region. One of the transcripts showed
      significant homology with the mouse and yeast SNM1/PSO(2) and was recently
      reported (Artemis) to be responsible for another T(-)B(-)NK(+) SCID condition
      (radiation sensitive SCID) in 13 patients of primarily European origin. In our
      evaluation of this gene, we have identified a unique nonsense mutation in 21
      SCIDA patients that is closely correlated to the founder haplotypes that we had
      previously identified. This nonsense founder mutation results in the truncation
      of the deduced protein product. The wild-type construct of the primary transcript
      can effectively complement the defective coding joint and reduced signal joint
      formation in SCIDA fibroblasts. The above results indicate that this SNM1-like
      gene (Artemis) is the gene responsible for SCIDA. We also discovered three
      additional alternative exons and detected at least six alternatively spliced
      SCIDA variants (SCIDA-V1, 2, 3, 4, 5, and 6) coexisting with the primary
      transcript in trace amounts. Finally, we found that the SCIDA primary transcript
      (Artemis) encodes a nuclear protein.

PMID- 12055249
TI  - Signaling through integrin LFA-1 leads to filamentous actin polymerization and
      remodeling, resulting in enhanced T cell adhesion.
AB  - The integrins can activate signaling pathways, but the final downstream outcome
      of these pathways is often unclear. This study analyzes the consequences of
      signaling events initiated by the interaction of the leukocyte integrin LFA-1
      with its ligand, dimeric ICAM-1. We show that the active form of LFA-1 regulates
      its own function on primary human T cells by directing the remodeling of the F
      actin cytoskeleton to strengthen T cell adhesion to ICAM-1. Confocal microscopy
      revealed that both F-actin bundling and overall levels of F-actin are increased
      in the ICAM-1-adhering T cells. This increase in F-actin levels and change in F
      actin distribution was quantitated for large numbers of T cells using the
      technique of laser scanning cytometry and was found to be significant. The study
      went on to show that clustering of conformationally altered LFA-1 is essential
      for the changes in F-actin, and a model is proposed in which clustered, high
      avidity T cell LFA-1, interacting with multivalent ICAM-1, causes LFA-1
      signaling, which results in F-actin polymerization and higher-order F-actin
      bundling. The findings demonstrate that LFA-1 acts not only as an adhesion
      receptor but also as a signaling receptor by actively initiating the F-actin
      reorganization that is essential for many T cell-dependent processes.

PMID- 12055250
TI  - Synaptic transfer by human gamma delta T cells stimulated with soluble or
      cellular antigens.
AB  - B, alpha beta T, and NK lymphocytes establish immunological synapses (IS) with
      their targets to enable recognition. Transfer of target cell-derived Ags together
      with proximal molecules onto the effector cell appears also to occur through
      synapses. Little is known about the molecular basis of this transfer, but it is
      assumed to result from Ag receptor internalization. Because human gamma delta T
      cells recognize soluble nonpeptidic phosphoantigens as well as tumor cells such
      as Daudi, it is unknown whether they establish IS with, and extract molecules
      from, target cells. Using flow cytometry and confocal microscopy, we show in this
      work that Ag-stimulated human V gamma 9/V delta 2 T cells conjugate to, and
      perform molecular transfer from, various tumor cell targets. The molecular
      transfer appears to be linked to IS establishment, evolves in a dose-dependent
      manner in the presence of either soluble or cellular Ag, and requires gamma delta
      TCR ligation, Src family kinase signaling, and participation of the actin
      cytoskeleton. Although CD45 exclusion characterized the IS performed by gamma
      delta T cells, no obvious capping of the gamma delta TCR was detected. The
      synaptic transfer mediated by gamma delta T cells involved target molecules
      unrelated to the cognate Ag and occurred independently of MHC class I expression
      by target cells. From these observations, we conclude that despite the particular
      features of gamma delta T cell activation, both synapse formation and molecular
      transfer of determinants belonging to target cell characterize gamma delta T cell
      recognition of Ags.

PMID- 12055251
TI  - Memory Th2 effector cells can develop in the absence of B7-1/B7-2, CD28
      interactions, and effector Th cells after priming with an intestinal nematode
      parasite.
AB  - B7-1/B7-2 interactions are required for many Th2-cell mediated primary immune
      responses including the response that follows infection with the intestinal
      nematode parasite, Heligmosomoides polygyrus. However, few studies have examined
      the role of B7-1/B7-2/CD28 interactions in the development of a Th2 memory immune
      response. We examined the development of the memory Th2 response to H. polygyrus
      in BALB/c mice deficient in both B7-1 and B7-2 (B7-1/B7-2(-/-)) and in BALB/c
      mice deficient in CD28 (CD28(-/-)). Following primary inoculation with H.
      polygyrus, adult worms in the gut were cleared with an anti-helminthic drug and
      mice were subsequently challenge-inoculated with H. polygyrus larvae. The memory
      Th2 response is readily distinguished by its inhibitory effect on adult worm
      maturation, resulting in marked reductions in adult worm egg production that are
      not observed during the primary immune response. Following H. polygyrus challenge
      inoculation, comparable decreases in egg production and similar increases in
      mesenteric lymph node cell IL-4 production were observed in B7-1/B7-2(-/-) and B7
      1/B7-2(+/+) mice. However, elevations in total serum IgG1 and IgE were reduced,
      while increases in serum Ag-specific IgG1 and IgE and germinal center formation
      were blocked in H. polygyrus-challenged B7-1/B7-2(-/-) mice. In contrast, in H.
      polygyrus-challenged CD28(-/-) mice, marked elevations in Ag-specific IgG1 and
      IgE and increased germinal center formation were observed. The results of these
      studies demonstrate that effector Th2 memory cells that produce IL-4 and mediate
      host defense can develop when B7-1/B7-2 interactions, and associated effector Th2
      cell development, are blocked during priming. However, humoral immunity is
      impaired and differentially affected in B7-1/B7-2(-/-) mice and CD28(-/-) mice
      following H. polygyrus challenge.

PMID- 12055253
TI  - Mycobacterium tuberculosis promotes apoptosis in human neutrophils by activating
      caspase-3 and altering expression of Bax/Bcl-xL via an oxygen-dependent pathway.
AB  - In addition to direct bactericidal activities, such as phagocytosis and
      generation of reactive oxygen species (ROS), neutrophils can regulate the
      inflammatory response by undergoing apoptosis. We found that infection of human
      neutrophils with Mycobacterium tuberculosis (Mtb) induced rapid cell death
      displaying the characteristic features of apoptosis such as morphologic changes,
      phosphatidylserine exposure, and DNA fragmentation. Both a virulent (H37Rv) and
      an attenuated (H37Ra) strain of Mtb were equally effective in inducing apoptosis.
      Pretreatment of neutrophils with antioxidants or an inhibitor of NADPH oxidase
      markedly blocked Mtb-induced apoptosis but did not affect spontaneous apoptosis.
      Activation of caspase-3 was evident in neutrophils undergoing spontaneous
      apoptosis, but it was markedly augmented and accelerated during Mtb-induced
      apoptosis. The Mtb-induced apoptosis was associated with a speedy and transient
      increase in expression of Bax protein, a proapoptotic member of the Bcl-2 family,
      and a more prominent reduction in expression of the antiapoptotic protein Bcl
      x(L). Pretreatment with an inhibitor of NADPH oxidase distinctly suppressed the
      Mtb-stimulated activation of caspase-3 and alteration of Bax/Bcl-x(L) expression
      in neutrophils. These results indicate that infection with Mtb causes ROS
      dependent alteration of Bax/Bcl-x(L) expression and activation of caspase-3, and
      thereby induces apoptosis in human neutrophils. Moreover, we found that
      phagocytosis of Mtb-induced apoptotic neutrophils markedly increased the
      production of proinflammatory cytokine TNF-alpha by human macrophages. Therefore,
      the ROS-dependent apoptosis in Mtb-stimulated neutrophils may represent an
      important host defense mechanism aimed at selective removal of infected cells at
      the inflamed site, which in turn aids the functional activities of local
      macrophages.

PMID- 12055252
TI  - Murine Lyme arthritis development mediated by p38 mitogen-activated protein
      kinase activity.
AB  - Borrelia burgdorferi, the Lyme disease agent, causes joint inflammation in an
      experimental murine model. Inflammation occurs, in part, due to the ability of B.
      burgdorferi to induce the production of proinflammatory cytokines and a strong
      CD4(+) T helper type 1 response. The mechanisms by which spirochetes induce these
      responses are not completely known, although transcription factors, such as NF
      kappa B in phagocytic cells, initiate the proinflammatory cytokine burst. We show
      here that the mitogen-activated protein (MAP) kinase of 38 kDa (p38 MAP kinase)
      is involved in the proinflammatory cytokine production elicited by B. burgdorferi
      Ags in phagocytic cells and the development of murine Lyme arthritis. B.
      burgdorferi Ags activated p38 MAP kinase in vitro, and the use of a specific
      inhibitor repressed the spirochete-induced production of TNF-alpha. The infection
      of mice that are deficient for a specific upstream activator of the kinase, MAP
      kinase kinase 3, resulted in diminished proinflammatory cytokine production and
      the development of arthritis, without compromising the ability of CD4(+) T cells
      to respond to borrelial Ags or the production of specific Abs. Overall, these
      data indicated that the p38 MAP kinase pathway plays an important role in B.
      burgdorferi-elicited inflammation and point to potential new therapeutic
      approaches to the treatment of inflammation induced by the spirochete.

PMID- 12055254
TI  - The Trypanosoma cruzi Tc52-released protein induces human dendritic cell
      maturation, signals via Toll-like receptor 2, and confers protection against
      lethal infection.
AB  - The intracellular protozoan parasite Trypanosoma cruzi is the etiological agent
      of Chagas disease. We have recently identified a T. cruzi-released protein
      related to thiol-disulfide oxidoreductase family, called Tc52, which is crucial
      for parasite survival and virulence. In vitro, Tc52 in combination with IFN-gamma
      activates human macrophages. In vivo, active immunization with Tc52 relieves the
      immunosuppression associated to acute infection and elicits a specific immune
      response. As dendritic cells (DC) have a central role in the initiation of immune
      responses, we investigated whether Tc52 may modulate DC activity. We show that
      Tc52 induces human DC maturation. Tc52-treated immature DC acquire CD83 and CD86
      expression, produce inflammatory chemokines (IL-8, monocyte chemoattractant
      protein-1, and macrophage-inflammatory protein-1 alpha), and present potent
      costimulatory properties. Tc52 binds to DC by a mechanism with the
      characteristics of a saturable receptor system and signals via Toll-like receptor
      2. While Tc52-mediated signaling involves its reduced glutathione-binding site,
      another portion of the molecule is involved in Tc52 binding to DC. Finally, we
      report that immunization with Tc52 protects mice in vivo against lethal infection
      with T. cruzi. Together these data evidence complex molecular interactions
      between the T. cruzi-derived molecule, Tc52, and DC, and suggest that Tc52 and
      related class of proteins might represent a new type of pathogen-associated
      molecular patterns. Moreover, the immune protection data suggest that Tc52 is
      among candidate molecules that may be used to design an optimal multicomponent
      vaccine to control T. cruzi infection.

PMID- 12055255
TI  - Protection from Streptococcus pneumoniae infection by C-reactive protein and
      natural antibody requires complement but not Fc gamma receptors.
AB  - Streptococcus pneumoniae is an important human pathogen and the most common cause
      of community-acquired pneumonia. Both adaptive and innate immune mechanisms
      provide protection from infection. Innate immunity to S. pneumoniae in mice is
      mediated by naturally occurring anti-phosphocholine (PC) Abs and complement. The
      human acute-phase reactant C-reactive protein (CRP) also protects mice from
      lethal S. pneumoniae infection. CRP and anti-PC Ab share the ability to bind to
      PC on the cell wall C-polysaccharide of S. pneumoniae and to activate complement.
      CRP and IgG anti-PC also bind to Fc gamma R. In this study, Fc gamma R- and
      complement-deficient mice were used to compare the mechanisms of protection
      conferred by CRP and anti-PC Ab. Injection of CRP protected wild-type, FcR gamma
      chain-, Fc gamma RIIb-, and Fc gamma RIII-deficient mice from infection.
      Complement was required for the protective effect of CRP as cobra venom factor
      treatment eliminated the effect of CRP in both gamma-chain-deficient and wild
      type mice, and CRP failed to protect C3- or C4-deficient mice from infection.
      Unexpectedly, gamma-chain-deficient mice were extremely sensitive to pneumococcal
      infection. This sensitivity was associated with low levels of natural anti-PC Ab.
      Gamma-chain-deficient mice immunized with nonencapsulated S. pneumoniae produced
      both IgM- and IgG PC-specific Abs, were protected from infection, and were able
      to clear the bacteria from the bloodstream. The protection provided by
      immunization was eliminated by complement depletion. The results show that in
      this model of systemic infection with highly virulent S. pneumoniae, protection
      from lethality by CRP and anti-PC Abs requires complement, but not Fc gamma R.

PMID- 12055256
TI  - Organ-specific CD4+ T cell response during Listeria monocytogenes infection.
AB  - The immune response against the intracellular bacterium Listeria monocytogenes
      involves both CD4(+) and CD8(+) T cells. We used the MHC class II-presented
      peptide listeriolysin(189-201) to characterize the organ-specific CD4(+) T cell
      response during infection. Systemic listeriosis resulted in a strong peptide
      specific CD4(+) T cell response with frequencies of 1/100 and 1/30 CD4(+)
      splenocytes at the peak of primary and secondary response, respectively. This
      response was not restricted to lymphoid organs, because we detected specific
      CD4(+) T cells in all tissues analyzed. However, the tissue distribution of the T
      cell response was dependent on the route of infection. After i.v. infection, the
      strongest CD4(+) T cell response and the highest levels of memory cells were
      observed in spleen and liver, the major sites of L. monocytogenes replication.
      After oral infection, we detected a strong response in the liver, the lamina
      propria, and the intestinal epithelium. These tissues also harbored the highest
      frequencies of listeriolysin(189-201)-specific CD4(+) memory T cells 5-8 wk post
      oral infection. Our results show that kinetics and magnitude of the CD4(+) T cell
      response and the accumulation of CD4(+) memory T cells depend on the route of
      infection and are regulated in a tissue-specific way.

PMID- 12055257
TI  - Inhibition of CXCR4-tropic HIV-1 infection by lipopolysaccharide: evidence of
      different mechanisms in macrophages and T lymphocytes.
AB  - Bacterial LPS protects primary human macrophages from infection by CCR5-tropic
      HIV-1 isolates through the release of the CC chemokines RANTES and macrophage
      inflammatory protein-1 alpha and -1 beta. Here, we show that LPS also suppresses
      infection of macrophages by CXCR4-tropic HIV-1 isolates. A marked down-regulation
      of both CD4 and CXCR4 expression was associated with this effect. Furthermore, a
      soluble factor(s) released by macrophages upon LPS treatment inhibited infection
      with CXCR4-tropic HIV-1 isolate viruses in both macrophages and T lymphocytes.
      Infection of both cell types appeared to be blocked at the level of viral entry
      and was independent of stromal cell-derived factor-1, the only known natural
      ligand of CXCR4. Moreover, the suppressive effect of LPS was unrelated to the
      release of IFN-alpha and -beta, macrophage-derived chemokine, leukemia inhibitory
      factor, or TNF-alpha. These results suggest the existence of potent HIV-1
      inhibitory factor(s), uncharacterized to date, released by activated cells of the
      mononuclear phagocytic system.

PMID- 12055258
TI  - The role of lipopolysaccharide binding protein in resistance to Salmonella
      infections in mice.
AB  - Polymorphonuclear leukocytes (PMN) and LPS-binding protein (LBP) are both
      components of the innate immune system. LBP is a plasma protein that binds to
      lipid A and enhances the biological activity of LPS 100- to 1000-fold. Recently
      it was reported that LBP-deficient mice are more susceptible to Salmonella
      typhimurium infection. Here we report that LBP KO mice are more susceptible to
      Salmonella peritonitis, but not to oral or i.v. infection. LBP knockout (KO) mice
      responded normally to i.p. injections of Staphylococcus aureus and casein, but
      not to i.p. injection of S. typhimurium or Salmonella LPS. Mice with a mutation
      in Toll-like receptor 4 (C3H/HeJ) have a similar defect in PMN chemotaxis. In
      normal mice S. typhimurium stimulated production of the CXC chemokines macrophage
      inflammatory protein-2 and cytokine-induced neutrophil chemoattractant, but
      levels of cytokine-induced neutrophil chemoattractant and macrophage inflammatory
      protein-2 were greatly reduced in the LBP KO mice. LBP KO mice pretreated with
      casein to attract PMN in an LBP-independent manner were more resistant to
      Salmonella infection, but neutropenic mice were not protected by casein. Splenic
      TNF-alpha mRNA levels were also lower in LBP KO than in control mice infected
      with Salmonella. Since TNF-alpha can activate PMN, LBP KO mice may have both
      fewer and less active PMN in the first few hours after Salmonella are injected,
      making LBP KO mice more susceptible. This work confirms the importance of PMN in
      resistance to Salmonella infections and shows that this is facilitated by LBP.

PMID- 12055259
TI  - Involvement of suppressor of cytokine signaling-3 as a mediator of the inhibitory
      effects of IL-10 on lipopolysaccharide-induced macrophage activation.
AB  - Previous studies have shown that IL-10 can induce the expression of the
      suppressor of cytokine signaling 3 (SOCS-3) mRNA in human monocytes and
      neutrophils, suggesting that the capacity of IL-10 to inhibit the expression of
      LPS-inducible proinflammatory genes may depend on SOCS-3 induction. However, no
      direct experimental evidence has been provided to support such hypothesis.
      Herein, we show that stable transfection of SOCS-3 into the mouse macrophage cell
      line J774 resulted in an inhibition of NO, TNF-alpha, IL-6, and GM-CSF secretion
      in response to LPS at levels similar to those exerted by IL-10 in LPS-stimulated
      wild-type J774. Constitutive SOCS-3 expression also down-regulated the mRNA
      expression of inducible NO synthase and IL-6 and impaired the production of TNF
      alpha, mainly at a post-transcriptional level. In addition, SOCS-3-transfected
      cells displayed a constitutive expression of the IL-1R antagonist gene,
      consistent with the observation that IL-10 enhances IL-1R antagonist mRNA in LPS
      stimulated wild-type cells. Furthermore, in peritoneal macrophages harvested from
      mice carrying heterozygous disruption of the SOCS-3 gene, IL-10 was less
      effective in repressing LPS-stimulated TNF-alpha and NO production. Taken
      together, our data show that SOCS-3 inhibits LPS-induced macrophage activation,
      strongly supporting the idea that it plays a role in the molecular mechanism by
      which IL-10 down-modulates the effector functions of LPS-activated macrophages.
      Finally, we show that forced expression of SOCS-3 significantly suppresses the
      ability of IL-10 to trigger tyrosine phosphorylation of STAT3. Therefore, SOCS-3
      functions both as an LPS signal inhibitor and as a negative feedback regulator of
      IL-10/STAT3 signaling.

PMID- 12055261
TI  - IFN-gamma-inducible T cell alpha chemoattractant is a potent stimulator of normal
      human blood T lymphocyte transendothelial migration: differential regulation by
      IFN-gamma and TNF-alpha.
AB  - Previous studies have shown that the CXC chemokine, IFN-gamma-inducible T cell
      alpha chemoattractant (I-TAC), was chemotactic for IL-2-activated human T
      lymphocytes, which express abundant CXCR3. However, because most memory T
      lymphocytes are also CXCR3(+), the ability of I-TAC to promote the migration of
      normal human blood T cells across HUVEC monolayers in Transwell chambers was
      examined. I-TAC induced a marked (4- to 6-fold) increase in transendothelial
      migration (TEM) of T cells across unstimulated HUVEC from 5.6 to 28% of input T
      cells and was substantially more active than IFN-gamma-inducible protein-10,
      another CXCR3 ligand. I-TAC significantly enhanced TEM of T cells across TNF
      alpha, but not across IFN-gamma or IFN-gamma plus TNF-alpha-activated HUVEC. IFN
      gamma or IFN-gamma plus TNF-alpha-activated HUVEC produced substantial amounts of
      I-TAC, in contrast to TNF-alpha-treated EC. Both CD4(+) and CD8(+) T cells
      migrated in response to I-TAC to a similar extent, while memory T cells migrated
      several fold better than naive T cells. Blockade of LFA-1 strongly inhibited I
      TAC-induced T cell TEM across unstimulated HUVEC, and approximately 50-60% of the
      TEM across cytokine-activated HUVEC. However, blocking both LFA-1 and very late
      Ag-4 abolished I-TAC induced T cell TEM. In vivo significant levels of I-TAC were
      detected in arthritic synovial fluid. Thus, I-TAC is one of the most potent
      chemoattractants of normal human blood CD4 and CD8 T cell TEM and is likely a
      major mediator of blood memory T lymphocyte migration to inflammation.

PMID- 12055260
TI  - Nerve growth factor activates mast cells through the collaborative interaction
      with lysophosphatidylserine expressed on the membrane surface of activated
      platelets.
AB  - Effect of nerve growth factor (NGF) on platelet-associated mast cell activation
      was investigated. Although neither NGF alone nor platelets alone induced
      significant 5-hydroxytriptamine (5-HT) release from rat peritoneal mast cells,
      marked 5-HT release was detected when costimulated with NGF and calcium ionophore
      activated platelets. This response reached maximal levels as early as 5 min after
      the initiation of the coincubation and was completely blocked by anti-NGF Ab or
      by an inhibitor for a tyrosine kinase of the trkA NGF receptor. Paraformaldehyde
      fixed platelets activated with either calcium ionophore or thrombin exhibited the
      collaborative ability, suggesting the possible involvement of some membrane
      molecules expressed on activated platelets in mast cell activation. Because
      activation of platelets induced expression of phosphatidylserine (PS) and/or
      lysoPS on membrane surface, and since lysoPS, unlike PS, initiated the NGF
      induced 5-HT release, lysoPS expressed on activated platelets may be involved in
      the mast cell activation. Moreover, intradermal injection of NGF and activated
      platelets into the rat skin increased local vascular permeability. These findings
      suggested that NGF collaboratively worked with membrane lysoPS of activated
      platelets to induce mast cell activation. Thus, NGF released in response to
      inflammatory stimuli may contribute to mast cell activation in collaboration with
      locally activated platelets in the process of inflammations and tissue repair.

PMID- 12055262
TI  - Protein kinase R regulates double-stranded RNA induction of TNF-alpha but not IL
      1 beta mRNA in human epithelial cells.
AB  - Epithelial cells represent the initial site of respiratory viral entry and the
      first line of defense against such infections. This early antiviral response is
      characterized by an increase in the production of proinflammatory cytokines such
      as TNF-alpha and IL-1 beta. dsRNA, which is a common factor present during the
      life cycle of both DNA and RNA viruses, is known to induce TNF-alpha and IL-1
      beta in a variety of cells. In this work we provide data showing that dsRNA
      treatment induces TNF-alpha and IL-1 beta in human lung epithelial cells via two
      different mechanisms. Our data show that dsRNA activation of dsRNA-activated
      protein kinase (PKR) is associated with induction of TNF-alpha but not IL-1 beta
      expression. An inhibitor of PKR activation blocked the dsRNA-induced elevations
      in TNF-alpha but not IL-1 beta mRNA in epithelial cells. Data obtained from
      infection of epithelial cells with a vaccinia virus lacking the PKR inhibitory
      polypeptide, E3L, revealed that PKR activation was essential for TNF-alpha but
      not for IL-1 beta expression. In this report, we provide experimental support for
      the differential regulation of proinflammatory cytokine expression by dsRNA and
      viral infections in human airway epithelial cells.

PMID- 12055263
TI  - Absence of the P2X7 receptor alters leukocyte function and attenuates an
      inflammatory response.
AB  - When challenged with extracellular ATP, leukocytes respond and activate processes
      attributed to the P2X(7) receptor (P2X(7)R), an unusual ligand-gated ion channel.
      To prove P2X(7)R involvement, blood samples from P2X(7)R-deficient mice were
      characterized. Monocytes and lymphocytes associated with wild-type blood
      responded to ATP and underwent volume/shape changes and shed L-selectin. In
      contrast, leukocytes from P2X(7)R-deficient animals demonstrated no change in
      physical properties or L-selectin expression following ATP challenge. Blood
      stimulated with LPS or ATP individually generated minimal quantities of the
      leaderless polypeptide IL-1 beta, but sequential treatment of wild-type, but not
      P2X(7)R-deficient, blood with LPS and ATP yielded large amounts of cell-free
      cytokine. Based on these differences, wild-type and P2X(7)R-deficient animals
      were compared following induction of monoclonal anti-collagen-induced arthritis.
      Ab-treated wild-type animals subsequently challenged with LPS developed inflamed,
      swollen paws; their joint cartilage demonstrated lesions, loss of proteoglycan
      content, and the presence of collagen degradation products. P2X(7)R-deficient
      animals subjected to the same challenge were markedly less affected; both the
      incidence and severity of disease were reduced. These data indicate that ATP does
      act via the P2X(7)R to affect leukocyte function and that the P2X(7)R can serve
      as an important component of an in vivo inflammatory response.

PMID- 12055264
TI  - Fgr deficiency results in defective eosinophil recruitment to the lung during
      allergic airway inflammation.
AB  - Using a mouse model of allergic lung inflammation, we found that mice deficient
      of Fgr, a Src family tyrosine kinase highly expressed in myelomonocytic cells,
      fail to develop lung eosinophilia in response to repeated challenge with
      aerosolized OVA. Both tissue and airway eosinophilia were markedly reduced in
      fgr(-/-) mice, whereas mice with the sole deficiency of Hck, another Src family
      member, responded normally. Release of allergic mediators, such as histamine, IL
      4, RANTES/CCL5, and eotaxin/CCL11, in the airways of OVA-treated animals was
      equal in wild-type and fgr(-/-) mice. However, lung eosinophilia in Fgr-deficient
      mice correlated with a defective accumulation of GM-CSF and IL-5 in the airways,
      whereas secretion of these cytokines by spleen cells in response to OVA was
      normal. Examination of mRNA expression in whole lung tissue allowed us to detect
      comparable expression of transcripts for eotaxin/CCL11, macrophage-inflammatory
      protein-1 alpha/CCL3, macrophage-inflammatory protein-1 beta/CCL4, monocyte
      chemoattractant protein-1/CCL2, TCA-3/CCL1, IL-4, IL-10, IL-2, IL-3, IL-9, IL-15,
      and IFN-gamma in OVA-sensitized wild-type and fgr(-/-) mice. In contrast, the
      increase in IL-5 and IL-13 mRNA expression was lower in fgr(-/-) compared with
      wild-type mice. These findings suggest that deficiency of Fgr results in a marked
      reduction of lung eosinophilia and the establishment of a positive feedback loop
      based on autocrine secretion of eosinophil-active cytokines. These results
      identify Fgr as a novel pharmacological target to control allergic inflammation.

PMID- 12055265
TI  - Absence of platelet endothelial cell adhesion molecule-1 (CD31) leads to
      increased severity of local and systemic IgE-mediated anaphylaxis and modulation
      of mast cell activation.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a newly assigned
      member of the Ig-immunoreceptor tyrosine-based inhibitory motif superfamily, and
      its functional role is suggested to be an inhibitory receptor that modulates
      immunoreceptor tyrosine-based activation motif-dependent signaling cascades. In
      this study, we hypothesized that PECAM-1 plays an essential in vivo role as a
      counterregulator of immediate hypersensitivity reactions. We found that PECAM-1
      was highly expressed on the surface of immature bone marrow mast cells and at a
      lower density on mature peritoneal mast cells. Examination of skin biopsies from
      PECAM-1(+/+) and PECAM-1(-/-) mice revealed that absence of PECAM-1 did not
      affect mast cell development or the capacity of mast cells to populate tissues.
      To examine whether the absence of PECAM-1 would influence immediate
      hypersensitivity reactions, PECAM-1(+/+) and PECAM-1(-/-) mice were presensitized
      with anti-DNP mouse IgE and then challenged 20 h later with DNP-BSA or PBS. PECAM
      1(-/-) mice exhibited elevated serum histamine concentrations after Ag
      stimulation compared with PECAM-1(+/+) mice, indicating an increased severity of
      systemic IgE-mediated anaphylaxis. PECAM-1(-/-) mice have increased sensitivity
      to local cutaneous IgE-dependent anaphylaxis compared with PECAM-1(+/+) mice, as
      assessed by greater tissue swelling of their ears and mast cell degranulation in
      situ. PECAM-1(-/-) bone marrow mast cells showed enhanced dense granule serotonin
      release after Fc epsilon RI cross-linking in vitro. These results suggest that
      PECAM-1 acts as a counterregulator in allergic disease susceptibility and
      severity and negatively modulates mast cell activation.

PMID- 12055266
TI  - Resistance to adjuvant arthritis is due to protective antibodies against heat
      shock protein surface epitopes and the induction of IL-10 secretion.
AB  - Adjuvant arthritis (AA) is an experimental model of autoimmune arthritis that can
      be induced in susceptible strains of rats such as inbred Lewis upon immunization
      with CFA. AA cannot be induced in resistant strains like Brown-Norway or in Lewis
      rats after recovery from arthritis. We have previously shown that resistance to
      AA is due to the presence of natural as well as acquired anti-heat shock protein
      (HSP) Abs. In this work we have studied the fine specificity of the protective
      anti-HSP Abs by analysis of their interaction with a panel of overlapping
      peptides covering the whole HSP molecule. We found that arthritis-susceptible
      rats lack Abs to a small number of defined epitopes of the mycobacterial HSP65.
      These Abs are found naturally in resistant strains and are acquired by Lewis rats
      after recovery from the disease. Active vaccination of Lewis rats with the
      protective epitopes as well as passive vaccination with these Abs induced
      suppression of arthritis. Incubation of murine and human mononuclear cells with
      the protective Abs induced secretion of IL-10. Analysis of the primary and
      tertiary structure of the whole Mycobacterium tuberculosis HSP65 molecule
      indicated that the protective epitopes are B cell epitopes with nonconserved
      amino acid sequences found on the outer surface of the molecule. We conclude that
      HSP, the Ag that contains the pathogenic T cell epitopes in AA, also contains
      protective B cell epitopes exposed on its surface, and that natural and acquired
      resistance to AA is associated with the ability to respond to these epitopes.

PMID- 12055267
TI  - TGF-beta 1 as an enhancer of Fas-mediated apoptosis of lung epithelial cells.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) has important roles in lung
      fibrosis and the potential to induce apoptosis in several types of cells. We
      previously demonstrated that apoptosis of lung epithelial cells induced by Fas
      ligation may be involved in the development of pulmonary fibrosis. In this study,
      we show that TGF-beta1 induces apoptosis of primary cultured bronchiolar
      epithelial cells via caspase-3 activation and down-regulation of cyclin-dependent
      kinase inhibitor p21. Concentrations of TGF-beta 1 that were not sufficient to
      induce apoptosis alone could enhance agonistic anti-Fas Ab or rFas ligand
      mediated apoptosis of cultured bronchiolar epithelial cells. Soluble Fas ligand
      in the bronchoalveolar lavage fluid (BALF) from patients with idiopathic
      pulmonary fibrosis (IPF) also induced apoptosis of cultured bronchiolar
      epithelial cells that was significantly attenuated by anti-TGF-beta Ab.
      Otherwise, BALF from patients with hypersensitivity pneumonitis (HP) could not
      induce apoptosis on bronchiolar epithelial cells, despite its comparable amounts
      of soluble Fas ligand. The concentrations of TGF-beta 1 in BALF from patients
      with IPF were significantly higher compared with those in BALF from patients with
      HP or controls. Furthermore, coincubation with the low concentration of TGF-beta
      1 and HP BALF created proapoptotic effects comparable with the IPF BALF. In vivo,
      the administration of TGF-beta 1 could enhance Fas-mediated epithelial cell
      apoptosis and lung injury via caspase-3 activation in mice. Our results
      demonstrate a novel role of TGF-beta 1 in the pathophysiology of pulmonary
      fibrosis as an enhancer of Fas-mediated apoptosis of lung epithelial cells.

PMID- 12055268
TI  - Suppression of autoimmune diabetes by viral IL-10 gene transfer.
AB  - Th1 cell activation and cytokine production shift the balance between Th1 and
      Th2, favoring the up-regulation of proinflammatory activity that leads to
      destruction of insulin-producing pancreatic beta cells in type 1 diabetes. Th2
      type cytokines, such as IL-10, have immune regulatory function. Administration of
      IL-10, or IL-10 gene transfer, prevents autoimmune diabetes in nonobese diabetic
      (NOD) mice. However, constant administration of purified rIL-10 is not practical
      for long-term therapy to prevent diabetes. In this study, we transferred the BCRF
      1 gene, an open reading frame in the Epstein-Barr viral genome with remarkable
      homology to mouse IL-10 (viral IL-10 or vIL-10), by an adeno-associated viral
      (AAV) vector to NOD mice to attain sustained vIL-10 gene expression. Like
      endogenous mouse IL-10, vIL-10 has potent immunoregulatory and immunosuppressive
      functions, but can be specifically distinguished from endogenous mouse IL-10 for
      monitoring of the transgene expression. A single systemic administration of AAV
      vIL-10 significantly reduced insulitis and prevented diabetes development in NOD
      mice. This protective effect correlated with sustained transgene expression and
      protein production. Moreover, splenocytes from the treated mice blocked diabetes
      transfer to NOD recipients, suggesting that vIL-10 induces an active suppression
      of autoimmunity. This study provides evidence to support the possibility of using
      vIL-10 gene therapy to prevent type 1 diabetes.

PMID- 12055269
TI  - Developmental and functional defects of thymic and epidermal V gamma 3 cells in
      IL-15-deficient and IFN regulatory factor-1-deficient mice.
AB  - In this study, the role of IL-15 and its regulation by the transcription factor
      IFN regulatory factor-1 (IRF-1) in murine V gamma 3 T cell development and
      activity is assessed. Compared with wild-type (WT) mice, reduced numbers of
      mature V gamma 3 cells were found in the fetal thymus of IL-15(-/-) mice, while
      IRF-1(-/-) mice displayed normal frequencies. V gamma 3(+) dendritic epidermal T
      cells (DETCs) were absent in IL-15(-/-) mice but present in IRF-1(-/-) mice.
      DETCs from IRF-1(-/-) mice displayed morphologically a less mature phenotype and
      showed different emergence kinetics during ontogeny. This corresponded with lower
      IL-15 mRNA levels in the skin epidermis. Comparable levels of IL-7 were found in
      the skin of WT and IL-15(-/-) mice. Adoptive transfer experiments of WT fetal
      thymocytes into IL-15(-/-) mice did not result in the development of V gamma 3(+)
      DETCs, confirming the nonredundant role of IL-15 in the skin during DETC
      development. In vitro, cytolytic activity of IL-15(-/-) V gamma 3 cells was
      normal after stimulation with IL-15 and was further enhanced by addition of IL
      12. In contrast, cytolytic activity of IRF-1(-/-) V gamma 3 cells remained
      defective after stimulation with IL-15 in combination with IL-12. These data
      suggest that IL-15 is redundant for the development and/or survival of mature V
      gamma 3 cells in the fetal thymus, whereas it is essential for the localization
      of V gamma 3 cells in the skin. Furthermore, a possible role for IRF-1 in
      inducing morphological maturation of DETCs and cytolytic capacity of V gamma 3
      cells is suggested.

PMID- 12055270
TI  - Impaired proliferative response of V alpha 24 NKT cells from cancer patients
      against alpha-galactosylceramide.
AB  - Human invariant V alpha 24(+) NKT cells are a relatively new subpopulation of
      lymphocytes. It has been reported that V alpha 24 NKT cells are significantly
      involved in some human diseases. We have evaluated the number and function of V
      alpha 24 NKT cells in both healthy volunteers and cancer patients. In this study
      we found that V alpha 24 NKT cells in unfractionated PBMCs obtained from cancer
      patients did not respond efficiently to alpha-galactosylceramide (alpha-GalCer)
      in vitro. Thus, their proportion after stimulation with alpha-GalCer was smaller
      than that found in healthy volunteers. However, the cancer patients' V alpha 24
      NKT cells retained cytotoxic activity against malignant target cells, and they
      could efficiently proliferate to alpha-GalCer when fractionated by sorting.
      Furthermore, we found that addition of G-CSF to the culture could restore the low
      proliferative response of V alpha 24 NKT cells from cancer patients. These
      results suggest that some functions of NKT cells in cancer patients are impaired,
      and this observation carries significant implications for immunotherapy-based
      cancer treatments.

PMID- 12055271
TI  - Reversible disruption of thymic function by steroid treatment.
AB  - The effect of steroid treatment on the thymic output of T cells was examined in
      an avian model. Recent thymic emigrants in chickens transiently express the
      chicken T cell Ag 1 thymocyte marker, and thymic function can be monitored
      indirectly by measuring the levels of TCR gene rearrangement excision circles in
      peripheral T cells. Both parameters were used to show that intensive steroid
      treatment induces thymic involution and a profound reduction in the supply of
      naive T cells to the periphery. Conversely, resident T cells in the peripheral
      lymphocyte pool were relatively spared. Thymopoiesis immediately recovered
      following cessation of steroid treatment, concurrent with restoration of the
      thymic output of newly formed T cells. Repopulation of the peripheral T cell pool
      recapitulated the ontogenetic pattern of gamma delta T cell replenishment before
      alpha beta T cell reseeding, thereby indicating the complete recovery of thymic
      function after a course of steroid treatment.

PMID- 12055275
TI  - Data acquisition in PET imaging.
AB  - Data acquisition is substantially different in PET than it is in planar nuclear
      medicine and SPECT. There is an entirely different set of definitions and
      considerations. The objective of this paper is to provide the reader with the
      terminology and understanding of how PET data are acquired and organized as well
      as the issues involved in choosing one approach over another. Sinograms and
      projection views will be presented as methods of storing and viewing raw PET
      data. Different approaches to increase axial sampling while maintaining a
      sufficient number of counts for each reconstructed slice are discussed, as well
      as the use of sinogram compression or "mashing" to reduce the storage
      requirements of raw PET data. The differences between 2-dimensional (2D) and 3
      dimensional (3D) PET and how storage of raw 3D data may differ from that of 2D
      data are described. The concept of "Michelograms" as a means of displaying the
      nature of the axial sampling in both 2D and 3D PET is discussed. After reading
      this paper, the reader will be able to describe 2 methods used to store and
      display raw PET data and compare them with methods used in SPECT. The reader will
      be able to define the terms "span" and "maximum ring difference" and describe how
      they relate to the axial sampling in 2D and 3D PET. The reader will also be able
      to list 3 ways in which 3D PET differs from 2D PET.

PMID- 12055276
TI  - Nuclear cardiology specialty examination technical report.

PMID- 12055272
TI  - Curcumin inhibits experimental allergic encephalomyelitis by blocking IL-12
      signaling through Janus kinase-STAT pathway in T lymphocytes.
AB  - Experimental allergic encephalomyelitis (EAE) is a CD4(+) Th1 cell-mediated
      inflammatory demyelinating autoimmune disease of the CNS that serves as an animal
      model for multiple sclerosis (MS). IL-12 is a proinflammatory cytokine that plays
      a crucial role in the induction of neural Ag-specific Th1 differentiation and
      pathogenesis of CNS demyelination in EAE and MS. Curcumin (1,7-Bis(4-hydroxy-3
      methoxyphenyl)-1,6-heptadiene-3,5-dione) is a naturally occurring polyphenolic
      phytochemical isolated from the rhizome of the medicinal plant Curcuma longa. It
      has profound anti-inflammatory activity and been traditionally used to treat
      inflammatory disorders. In this study we have examined the effect and mechanism
      of action of curcumin on the pathogenesis of CNS demyelination in EAE. In vivo
      treatment of SJL/J mice with curcumin significantly reduced the duration and
      clinical severity of active immunization and adoptive transfer EAE. Curcumin
      inhibited EAE in association with a decrease in IL-12 production from
      macrophage/microglial cells and differentiation of neural Ag-specific Th1 cells.
      In vitro treatment of activated T cells with curcumin inhibited IL-12-induced
      tyrosine phosphorylation of Janus kinase 2, tyrosine kinase 2, and STAT3 and
      STAT4 transcription factors. The inhibition of Janus kinase-STAT pathway by
      curcumin resulted in a decrease in IL-12-induced T cell proliferation and Th1
      differentiation. These findings highlight the fact that curcumin inhibits EAE by
      blocking IL-12 signaling in T cells and suggest its use in the treatment of MS
      and other Th1 cell-mediated inflammatory diseases.

PMID- 12055277
TI  - NMTCB report.

PMID- 12055279
TI  - Introduction to PET Instrumentation.

PMID- 12055280
TI  - The tadpole effect in Escherichia coli B/r.

PMID- 12055281
TI  - Escherichia coli's uropathogenic-specific protein: a bacteriocin promoting
      infectivity?

PMID- 12055282
TI  - 'New uses for an Old Enzyme'--the Old Yellow Enzyme family of flavoenzymes.

PMID- 12055283
TI  - Expression of fibronectin-binding protein FbpA modulates adhesion in
      Streptococcus gordonii.
AB  - Fibronectin binding is considered to be an important virulence factor in
      streptococcal infections. Adhesion of the oral bacterium Streptococcus gordonii
      to immobilized forms of fibronectin is mediated, in part, by a high molecular
      mass wall-anchored protein designated CshA. In this study, a second fibronectin
      binding protein of S. gordonii is described that has been designated as FbpA
      (62.7 kDa). This protein, which is encoded by a gene located immediately
      downstream of the cshA gene, shows 85 and 81% identity to the fibronectin-binding
      proteins PavA, of Streptococcus pneumoniae, and FBP54, of Streptococcus pyogenes,
      respectively. Purified recombinant FbpA bound to immobilized human fibronectin in
      a dose-dependant manner, and isogenic mutants in which the fbpA gene was
      inactivated were impaired in their binding to fibronectin. This effect was
      apparent only for cells in the exponential phase of growth, and was associated
      with reduced surface hydrophobicity and the surface expression of CshA. Cells in
      the stationary phase of growth were unaffected in their ability to bind to
      fibronectin. By utilizing gene promoter fusions with cat (encoding
      chloramphenicol O-acetyltransferase), it was demonstrated that cshA expression
      was down-regulated during the exponential phase of growth in the fbpA mutant.
      Expression of fbpA, but not cshA, was sensitive to atmospheric O2 levels, and was
      found to be up-regulated in the presence of elevated O2 levels. The results
      suggest that FbpA plays a regulatory role in the modulation of CshA expression
      and, thus, affects the adhesion of S. gordonii to fibronectin.

PMID- 12055284
TI  - Role of the Streptococcus gordonii SspB protein in the development of
      Porphyromonas gingivalis biofilms on streptococcal substrates.
AB  - Porphyromonas gingivalis is an aggressive periodontal pathogen that persists in
      the mixed-species plaque biofilm on tooth surfaces. P. gingivalis cells attach to
      the plaque commensal Streptococcus gordonii and this coadhesion event leads to
      the development of P. gingivalis biofilms. Binding of these organisms is
      multimodal, involving both the P. gingivalis major fimbrial FimA protein and the
      species-specific interaction of the minor fimbrial Mfa1 protein with the
      streptococcal SspB protein. This study examined the contribution of the Mfa1-SspB
      interaction to P. gingivalis biofilm formation. P. gingivalis biofilms readily
      formed on substrata of S. gordonii DL1 but not on Streptococcus mutans cells
      which lack a coadhesion-mediating homologue of SspB. An insertional inactivation
      of the mfa1 gene in P. gingivalis resulted in a phenotype deficient in S.
      gordonii binding and unable to form biofilms. Furthermore, analysis using
      recombinant streptococci and enterococci showed that P. gingivalis biofilms
      formed on Enterococcus faecalis strains expressing SspB or translational fusions
      of SspB with SpaP (the non-adherent SspB homologue in S. mutans) containing the
      P. gingivalis adherence domain (SspB adherence region, BAR) of SspB. In contrast,
      an isogenic Ssp null mutant of S. gordonii DL1 was unable to support biofilm
      growth, even though this strain bound to P. gingivalis FimA at levels similar to
      wild-type S. gordonii DL1. Finally, site-specific mutation of two functional
      amino acid residues in BAR resulted in SspB polypeptides that did not promote the
      development of P. gingivalis biofilms. These results suggest that the induction
      of P. gingivalis biofilms on a streptococcal substrate requires functional SspB
      minor fimbriae interactions.

PMID- 12055285
TI  - The complete nucleotide sequence and environmental distribution of the cryptic,
      conjugative, broad-host-range plasmid pIPO2 isolated from bacteria of the wheat
      rhizosphere.
AB  - Plasmid pIPO2 is a cryptic, conjugative, broad-host-range plasmid isolated from
      the wheat rhizosphere. It efficiently self-transfers between alpha, beta and
      gamma Proteobacteria and has a mobilizing/retromobilizing capacity for IncQ
      plasmids. The complete nucleotide sequence of pIPO2 is presented on the basis of
      its mini-Tn5::luxABtet-tagged derivative, pIPO2T. The pIPO2 sequence is 39815 bp
      long and contains at least 43 complete ORFs. Apart from a suite of ORFs with
      unknown function, all of the genes carried on pIPO2 are predicted to be involved
      in plasmid replication, maintenance and conjugative transfer. The overall
      organization of these genes is different from previously described plasmids, but
      is similar to the genetic organization seen in pSB102, a conjugative plasmid
      recently isolated from the bacterial community of the alfalfa rhizosphere. The
      putative conjugative transfer region of pIPO2 covers 23 kb and contains the genes
      required for DNA processing (Dtr) and mating pair formation (Mpf). The
      organization of these transfer genes in pIPO2 is highly similar to the genetic
      organization seen in the environmental plasmid pSB102 and in pXF51 from the plant
      pathogen Xylella fastidiosa. Plasmids pSB102 and pXF51 have recently been
      proposed to form a new family of environmental broad-host-range plasmids. Here it
      is suggested that pIPO2 is a new member of this family. The proposed Mpf system
      of pIPO2 shares high amino acid sequence similarity with equivalent VirB proteins
      from the type IV secretion system of Brucella spp. Sequence information was used
      to design primers specific for the detection of pIPO2. Environmental DNA from a
      range of diverse habitats was screened by PCR with these primers. Consistently
      positive signals for the presence of pIPO2 were obtained from a range of soil
      related habitats, including the rhizospheres of young wheat plants, of field
      grown oats and of grass (all gramineous plants), as well as from the rhizosphere
      of tomato plants. These data add to the growing evidence that plasmids carry
      advantageous genes with as yet undefined functions in plant-associated
      communities.

PMID- 12055286
TI  - Evolutionary and functional analyses of variants of the toxin-coregulated pilus
      protein TcpA from toxigenic Vibrio cholerae non-O1/non-O139 serogroup isolates.
AB  - The toxin-coregulated pilus (TCP) is a critical determinant of the pathogenicity
      of Vibrio cholerae. This bundle-forming pilus is an essential intestinal
      colonization factor and also serves as a receptor for CTXphi, the filamentous
      phage that encodes cholera toxin (CT). TCP is a polymer of repeating subunits of
      the major pilin protein TcpA and tcpA is found within the Vibrio pathogenicity
      island (VPI). In this study genetic variation at the tcpA locus in toxigenic
      isolates of V. cholerae was investigated and three novel TcpA sequences from V.
      cholerae strains V46, V52 and V54, belonging to serogroups O141, O37 and O8,
      respectively, were identified. These novel tcpA alleles grouped into three
      distinct clonal lineages. The polymorphisms in TcpA were predominantly located in
      the carboxyl region of TcpA in surface-exposed regions of TCP fibres. Comparison
      of the genetic diversity among V. cholerae isolates at the tcpA locus with that
      of aldA, another locus within the VPI, and mdh, a chromosomal locus, revealed
      that tcpA sequences are far more diverse than these other loci. Most likely, this
      diversity is a reflection of diversifying selection in adaptation to the host
      immune response or to CTXphi susceptibility. An assessment of the functional
      properties of the variant tcpA sequences in the non-O1 V. cholerae strains was
      carried out by analysing whether these strains could be infected by CTXphi and
      colonize the suckling mouse. Similar to El Tor strains of V. cholerae O1, in
      vitro CTXphi infection of these strains required the exogenous expression of
      toxT, suggesting that in these strains ToxT regulates TCP expression and that
      these TcpA variants can serve as CTXphi receptors. All the V. cholerae non-O1
      serogroup isolates tested were capable of colonizing the suckling mouse small
      intestine, suggesting that the different TcpA variants could function as
      colonization factors.

PMID- 12055287
TI  - Role of the Legionella pneumophila rtxA gene in amoebae.
AB  - Legionella pneumophila infects humans, causing Legionnaires' disease, from
      aerosols generated by domestic and environmental water sources. In aquatic
      environments L. pneumophila is thought to replicate primarily in protozoa. A
      'repeats in structural toxin' (RTX) gene, rtxA, from L. pneumophila was
      identified recently that plays a role in entry and replication in human
      macrophages and also has the ability to infect mice. However, the role of this
      gene in the interaction of L. pneumophila with environmental protozoa and its
      distribution in different Legionella species has not been examined. Southern
      analyses demonstrated that rtxA is present in all L. pneumophila isolates tested
      and correlates with species that have been shown to cause disease in humans. To
      evaluate the importance of rtxA in the interaction with protozoa a series of
      studies was carried out in an environmental host for L. pneumophila, Acanthamoeba
      castellanii. The L. pneumophila rtxA gene plays a role in both adherence and
      entry into A. castellanii similar to that observed in human monocytic cells.
      Furthermore, it was found that rtxA is involved in intracellular survival and
      trafficking. In addition to demonstrating involvement of rtxA in the interaction
      of L. pneumophila with host cells, these data support a role for this gene both
      during disease in humans and in environmental reservoirs.

PMID- 12055288
TI  - Mutational and transcriptional analysis of the Campylobacter jejuni flagellar
      biosynthesis gene flhB.
AB  - A Campylobacter jejuni gene encoding a homologue of the flagellar biosynthesis
      gene flhB was identified downstream of the peroxide stress defence gene ahpC.
      Insertional mutagenesis of the flhB gene rendered C. jejuni non-motile, with most
      cells aflagellate, although a small number expressed truncated flagella. The
      absence of FlhB also appeared to affect cell shape, as the majority of cells were
      straight rather than curved rods. Transcription of the flagellin gene flaA was
      significantly reduced in the C. jejuni flhB mutants, which also did not express
      significant amounts of flagellin proteins, indicating that FlhB is an essential
      protein for subsequent expression of flagellar genes. The transcription start
      site of the flhB gene, as determined by primer extension, was located 91 bp
      upstream of the flhB start codon, but no recognizable promoter sequence could be
      identified immediately upstream of this transcription start site. Transcriptional
      flhB::lacZ reporter gene fusions confirmed that the flhB gene has its own
      promoter region, is expressed at very low levels and is transcribed independently
      of ahpC, and that its transcription is not regulated by iron or growth phase.

PMID- 12055289
TI  - Genome plasticity in Yersinia pestis.
AB  - Yersinia pestis, the causative agent of bubonic plague, emerged recently (<20000
      years ago) as a clone of Yersinia pseudotuberculosis. There is scant evidence of
      genome diversity in Y. pestis, although it is possible to differentiate three
      biovars (antiqua, mediaevalis or orientalis) based on two biochemical tests.
      There are a few examples of restriction fragment length polymorphisms (RFLPs)
      within Y. pestis; however, their genetic basis is poorly understood. In this
      study, six difference regions (DFRs) were identified in Y. pestis, by using
      subtractive hybridization, which ranged from 4.6 to 19 kb in size. Four of the
      DFRs are flanked by insertion sequences, and their sequences show similarity to
      bacterial genes encoding proteins for flagellar synthesis, ABC transport, insect
      toxicity and bacteriophage functions. The presence or absence of these DFRs
      (termed the DFR profile) was demonstrated in 78 geographically diverse strains of
      Y. pestis. Significant genome plasticity was observed among these strains and
      suggests the acquisition and deletion of these DNA regions during the recent
      evolution of Y. pestis. Y. pestis biovar orientalis possesses DFR profiles that
      are different from antiqua and mediaevalis biovars, reflecting the recent origins
      of this biovar. Whereas some DFR profiles are specific for antiqua and
      mediaevalis, some DFR profiles are shared by both biovars. Furthermore, the
      progenitor of Y. pestis, Y. pseudotuberculosis (an enteric pathogen), possesses
      its own DFR profile. The DFR profiles detailed here demonstrate genome plasticity
      within Y. pestis, and they imply evolutionary relationships among the three
      biovars of Y. pestis, as well as between Y. pestis and Y. pseudotuberculosis.

PMID- 12055290
TI  - The membrane-bound respiratory chain of Pseudomonas pseudoalcaligenes KF707 cells
      grown in the presence or absence of potassium tellurite.
AB  - The respiratory chain of Pseudomonas pseudoalcaligenes KF707 in membranes
      isolated from cells grown in the presence or absence of the toxic oxyanion
      tellurite (TeO3(2-)) was examined. Aerobic growth in the absence of tellurite
      shows an NADH-dependent respiration which is 80% catalysed by the cytochrome
      (cyt) bc1-containing pathway leading to two terminal membrane-bound cyt c
      oxidases inhibited by different concentrations of KCN (IC50 0.2 and 1 microM). A
      third oxidase, catalysing the remaining 20% of the cyanide-resistant respiration
      and fully inhibited by 2-3 mM KCN, is also present; this latter pathway accounts
      for 60-70% of the total NADH-dependent respiration in membranes from cells grown
      in LB medium supplemented with potassium tellurite (35 microg x ml(-1)). Two high
      potential b-type haems (E(m,7) +395 and 318 mV) are redox centres of a membrane
      bound cyt c oxidase (possibly of the cbb3 type) which shows a 50% decrease of its
      activity in parallel with a similar decrease of the c-type haem content (mostly
      soluble cyt c) in membranes from tellurite-grown cells; the latter type of cells
      specifically contain a cyt b type at +203 mV (pH 9.0) which is likely to be
      involved in cyanide-resistant respiration. Comparison of the growth curve of
      KF707 cells in parallel with tellurite uptake showed that intracellular
      accumulation of tellurium (Te(0)) crystallites starts from the mid-exponential
      growth phase, whereas tellurite-induced changes of the respiratory chain are
      already evident during the early stages of growth. These data were interpreted as
      showing that reduction of tellurite to tellurium and tellurite-dependent
      modifications of the respiratory chain are unrelated processes in P.
      pseudoalcaligenes KF707.

PMID- 12055291
TI  - Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa
      PAO1 alginate, pyoverdin, elastase and LasA.
AB  - The pathogenesis of Pseudomonas aeruginosa is at least partially attributable to
      its ability to synthesize and secrete the siderophore pyoverdin and the two zinc
      metalloproteases elastase and LasA, and its ability to form biofilms in which
      bacterial cells are embedded in an alginate matrix. In the present study, a
      lysophospholipid, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate [also called
      monopalmitoylphosphatidic acid (MPPA)], which accumulates in inflammatory
      exudates, was shown to inhibit the extracellular accumulation of P. aeruginosa
      PAO1 alginate, elastase, LasA protease and the siderophore pyoverdin. MPPA also
      inhibited biofilm formation. The inhibitory effects of MPPA occur independently
      of rpoS expression and without affecting the accumulation of the autoinducers N
      (3-oxododecanoyl) homoserine lactone and N-butyryl-L-homoserine lactone, and may
      be due, at least in part, to the ability of MPPA to bind divalent cations.

PMID- 12055292
TI  - A third fatty acid delta9-desaturase from Mortierella alpina with a different
      substrate specificity to ole1p and ole2p.
AB  - A third gene (Delta9-3) encoding a fatty acid Delta9-desaturase was isolated from
      the oil-producing fungus Mortierella alpina. The predicted protein of 512 aa
      shared 53% sequence identity with the two fatty acid Delta9-desaturases, ole1p
      and ole2p, already described in this organism and contained three histidine
      boxes, four putative transmembrane domains and a C-terminal cytochrome b(5)
      fusion that are typical of most fungal membrane-bound fatty acid desaturases.
      However, unlike the M. alpina ole1 and ole2 genes, the Delta9-3 ORF failed to
      complement the Saccharomyces cerevisiae ole1 mutation. GC-MS analysis of fatty
      acid-supplemented ole1 yeast transformants containing the Delta9-3 gene indicated
      that this enzyme had negligible activity with endogenous palmitic acid (16:0) as
      substrate and moderate activity (30-65% desaturation) with endogenous stearic
      acid (18:0). Yeast transformants overexpressing any one of the three M. alpina
      fatty acid Delta9-desaturase genes or the S. cerevisiae OLE1 gene produced low
      amounts of hexacosenoic acid [26:1(n-9)], a fatty acid that is not normally
      present in yeast cells. It follows that these Delta9-desaturases may also display
      low n-9 desaturation activity with very long-chain saturated fatty acid
      substrates. Conversely, high levels of desaturase in the endoplasmic reticulum
      membrane of these yeast transformants may increase the availability of suitable
      monounsaturated substrates for fatty acid elongation.

PMID- 12055293
TI  - Phosphatidylinositol-4-phosphate 5-kinase activity is stimulated during
      temperature-induced morphogenesis in Candida albicans.
AB  - Phosphoinositides are important lipid signalling molecules in eukaryotic cells.
      Phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) catalyses the production of
      phosphatidylinositol 4,5-bisphosphate (PIP2), which stimulates phospholipase D1
      (PLD1) activity in mammalian and yeast cells. PLD1 catalyses the formation of
      phosphatidic acid (PA), which has been shown to activate PI4P5Ks in mammalian and
      Saccharomyces cerevisiae cells. In the present study, PI4P5K activity in the
      opportunistic pathogen Candida albicans was identified. A gene with significant
      sequence homology to the S. cerevisiae PI4P5K was cloned and designated MSS4.
      This gene was demonstrated to encode a functional PI4P5K by expression in S.
      cerevisiae. This enzyme was found to be membrane-associated and was stimulated by
      PA. Within the first 20 min after induction of polarized hyphal growth induced by
      a shift to elevated temperature, PI4P5K activity increased 2.5-fold. This
      stimulation was not observed when hyphae were induced by a combination of
      elevated temperature and serum. A lack of PLD1 activity resulted in the loss of
      induction of PI4P5K activity during the morphogenetic switch. Furthermore, the
      addition of propranolol attenuated the stimulation of PI4P5K activity during
      morphogenesis. These results suggest that PA derived from PLD1 activity
      stimulates C. albicans PI4P5K during the switch to the hyphal form under some
      conditions.

PMID- 12055294
TI  - Organization and characterization of the capsule biosynthesis locus of
      Streptococcus pneumoniae serotype 9V.
AB  - The capsular polysaccharide (CPS) synthesis locus of Streptococcus pneumoniae
      serotype 9V was amplified by long-range PCR and sequenced. The locus was 17368 bp
      in size and contained 15 ORFs. The genetic organization of the cluster shared
      many features with other S. pneumoniae capsule loci, including the presence of
      four putative regulatory genes at the 5' end. Comparative sequence analyses
      allowed putative functions to be assigned to each of the gene products. The ORFs
      appeared to encode, besides the four regulatory genes, five glycosyltransferases,
      two O-acetyltransferases, an N-acetylglucosamine 2-epimerase, a glucose 6
      dehydrogenase, an oligosaccharide transporter protein and a polysaccharide
      repeating unit polymerase. These functions covered the steps proposed in the CPS
      biosynthesis of serotype 9V. TLC of carbohydrate intermediates formed after
      incubation of bacterial membrane preparations with 14C-labelled precursors
      demonstrated that the fifth ORF (cps9vE) encoded a UDP-glucosyl-1-phosphate
      transferase. This function was confirmed with the help of a cps9vE mutant that
      carried a deletion of a guanine residue located adjacent to a stretch of
      adenines. The identification and characterization of the serotype 9V locus is a
      major step in unravelling the 9V capsule biosynthesis pathway and broadens the
      insight into the genetic diversity of the S. pneumoniae capsule loci.

PMID- 12055295
TI  - The Escherichia coli small heat-shock proteins IbpA and IbpB prevent the
      aggregation of endogenous proteins denatured in vivo during extreme heat shock.
AB  - The roles of the Escherichia coli IbpA and IbpB chaperones in protection of heat
      denatured proteins against irreversible aggregation in vivo were investigated.
      Overproduction of IbpA and IbpB resulted in stabilization of the denatured and
      reversibly aggregated proteins (the S fraction), which could be isolated from E.
      coli cells by sucrose gradient centrifugation. This finding is in agreement with
      the present model of the small heat-shock proteins' function, based mainly on in
      vitro studies. Deletion of the ibpAB operon resulted in almost twofold increase
      in protein aggregation and in inactivation of an enzyme (fructose-1,6-biphosphate
      aldolase) in cells incubated at 50 degrees C for 4 h, decreased efficiency of the
      removal of protein aggregates formed during prolonged incubation at 50 degrees C
      and affected cell viability at this temperature. IbpA/B proteins were not needed
      for removal of protein aggregates or for the enzyme protection/renaturation in
      cells heat shocked at 50 degrees C for 15 min. These results show that the IbpA/B
      proteins are required upon an extreme, long-term heat shock. Overproduction of
      IbpA but not IbpB caused an increase of the level of beta-lactamase precursor,
      which was localized in the S fraction, together with the IbpA protein, which
      suggests that the unfolded precursor binds to IbpA but not to IbpB. Although in
      the wild-type cells both E. coli small heat-shock proteins are known to localize
      in the S fraction, only 2% of total IbpB co-localized with the aggregated
      proteins in the absence of IbpA, while in the absence of IbpB, the majority of
      IbpA was present in the aggregates fraction.

PMID- 12055296
TI  - A novel extracytoplasmic phenol oxidase of Streptomyces: its possible involvement
      in the onset of morphogenesis.
AB  - Exogenous addition of copper stimulates cellular differentiation in Streptomyces
      spp. Several lines of evidence suggested a parallel correlation between the
      stimulatory effect of copper and phenol-oxidizing enzyme activities in
      Streptomyces griseus. Here a novel extracytoplasmic phenol oxidase (EpoA)
      associated with cellular development of this organism was identified and
      characterized. EpoA activity, examined by an in-gel stain procedure with N,N'
      dimethyl-p-phenylenediamine sulfate as a substrate, was repressed by glucose and
      induced by copper supplied in the medium. The enzyme activity was abolished and
      markedly reduced in the mutants forA-factor biosynthesis and amfR, respectively,
      which suggested that the activity of the enzyme depends on those essential
      regulators for morphogenesis in S. griseus. EpoA protein was purified to
      homogeneity and the N-terminal amino acid sequence was determined. A homologous
      sequence identified in the genomic database of Streptomyces coelicolorA3(2) was
      used as a probe to clone the complete epoA gene of S. griseus. The deduced amino
      acid sequence of EpoA revealed that the mature protein with a molecular mass of
      34 kDa was preceded by a signal peptide consisting of 34 aa, consistent with EpoA
      being a secreted enzyme. EpoA was predicted to be a laccase-type oxidase by not
      only the sequence similarity, but its substrate selectivity, oxidizing not
      tyrosine but dihydroxyphenylalanine (DOPA) to generate melanin pigment.
      Introduction of epoA on a plasmid partially restored both the EpoA activity and
      aerial mycelium productivity in an A-factor-deficient mutant. Exogenous
      supplementation of a substance synthesized by purified EpoA from DOPA stimulated
      cellular differentiation in S. griseus and several other species. Ultrafiltration
      indicated that the molecular mass of the putative stimulant synthesized by EpoA
      is between 500 and 1000 Da.

PMID- 12055297
TI  - Type II thioesterase from Streptomyces coelicolor A3(2).
AB  - Type I polyketide synthases (PKSs) are complexes of large, multimodular enzymes
      that catalyse biosynthesis of polyketide compounds via repetitive reaction
      sequences, during which each step is catalysed by a separate enzymic domain. Many
      type I PKSs, and also non-ribosomal peptide synthetase clusters, contain
      additional thioesterase genes located adjacent to PKS genes. These are discrete
      proteins called type II thioesterases (TE IIs) to distinguish them from chain
      terminating thioesterase (TE I) domains that are usually fused to the terminal
      PKS module. A gene of a new TE II, scoT, associated with the cluster of putative
      type I PKS genes from Streptomyces coelicolor A3(2), was found. The deduced amino
      acid sequence of the gene product shows extensive similarity to other authentic
      thioesterase enzymes, including conservation of characteristic motifs and
      residues involved in catalysis. When expressed in the heterologous host
      Streptomyces fradiae, scoT successfully complemented the resident TE II gene
      (tylO), and, by restoring a significant level of macrolide production, proved to
      be catalytically equivalent to the TylO protein. S1 nuclease mapping of scoT
      revealed a single potential transcription start point with expression being
      switched on for a short period of time during a transition phase of growth.

PMID- 12055299
TI  - A 5' stem-loop and ribosome binding but not translation are important for the
      stability of Bacillus subtilis aprE leader mRNA.
AB  - The Bacillus subtilis aprE leader is a determinant of extreme mRNA stability. The
      authors examined what properties of the aprE leader confer stability on an mRNA.
      The secondary structure of the aprE leader mRNA was analysed in vitro and in
      vivo, and mutations were introduced into different domains of an aprE leader-lacZ
      fusion. The half-lives of the corresponding transcripts were determined and beta
      galactosidase activities were measured. Removal of a stem-loop structure at the
      5' end or diminishing the strength of the RBS reduced the half-lives from more
      than 25 min to about 5 min. Interfering with translation by abolishing the start
      codon or creating an early stop codon had no or little effect on mRNA stability.
      The authors conclude that a 5' stem-loop and binding of ribosomes are necessary
      for the stability of aprE leader mRNA. The present results, together with a
      number of other data, suggest that translation of a B. subtilis mRNA is generally
      not important for its stability; the situation seems different in Escherichia
      coli. It is further concluded that the calculated strength of a B. subtilis RBS
      cannot be used to predict the stability of the corresponding transcript.

PMID- 12055298
TI  - Swarming motility in Bacillus cereus and characterization of a fliY mutant
      impaired in swarm cell differentiation.
AB  - This report describes a new behavioural response of Bacillus cereus that consists
      of a surface-induced differentiation of elongated and hyperflagellated swarm
      cells exhibiting the ability to move collectively across the surface of the
      medium. The discovery of swarming motility in B. cereus paralleled the isolation
      of a spontaneous non-swarming mutant that was found to carry a deletion of fliY,
      the homologue of which, in Bacillus subtilis, encodes an essential component of
      the flagellar motor-switch complex. However, in contrast to B. subtilis, the fliY
      mutant of B. cereus was flagellated and motile, thus suggesting a different role
      for FliY in this organism. The B. cereus mutant was completely deficient in
      chemotaxis and in the secretion of the L2 component of the tripartite pore
      forming necrotizing toxin, haemolysin BL, which was produced exclusively by the
      wild-type strain during swarm-cell differentiation. All the defects in the fliY
      mutant of B. cereus could be complemented by a plasmid harbouring the B. cereus
      fliY gene. These results demonstrate that the activity of fliY is required for
      swarming and chemotaxis in B. cereus, and suggest that swarm-cell differentiation
      is coupled with virulence in this organism.

PMID- 12055300
TI  - HPr kinase/phosphatase of Bacillus subtilis: expression of the gene and effects
      of mutations on enzyme activity, growth and carbon catabolite repression.
AB  - HPr kinase/phosphatase (HPrK/P) is the key protein in regulation of carbon
      metabolism in Bacillus subtilis and many other Gram-positive bacteria. Whether
      this enzyme acts as a kinase or phosphatase is determined by the nutrient status
      of the cell. Mutational analysis of residues in a Walker A box nucleotide-binding
      motif revealed that it is not only important for kinase but is also involved in
      phosphatase activity. In addition, a signature sequence specifically conserved
      among HPrK/P orthologues is required for phosphatase activity and may be involved
      in interaction with HPr/HPr-(Ser46)-P. Carbon catabolite repression was abolished
      in a B. subtilis strain expressing a mutant form of HPrK/P deficient in kinase
      and phosphatase activities. The growth characteristics of this strain were
      similar to those of the wild-type. In contrast, B. subtilis strains expressing
      HPrK/P with partial kinase and no phosphatase activities showed growth impairment
      but exhibited catabolite repression.

PMID- 12055301
TI  - Many carried meningococci lack the genes required for capsule synthesis and
      transport.
AB  - Of 830 Neisseria meningitidis isolates obtained from healthy carriers in Bavaria,
      Germany, 136 (16.4%) lacked the operons necessary for the synthesis, lipid
      modification, and transport of capsular polysaccharide. These operons were
      replaced by a non-coding intergenic region either 113 or 114 bp in length, termed
      here the capsule null locus (cnl). Comparisons of the nucleotide sequence of this
      region in the meningococcus and its acapsulate relatives, Neisseria gonorrhoeae
      and Neisseria lactamica, revealed six distinct sequence variants (cnl-1 to cnl
      6), with a total of 10 nucleotide substitutions and three indels. With the
      exception of one 4 bp insertion, which was unique to a gonococcal isolate, all of
      the individual sequence changes were present in the N. lactamica isolates
      examined. The meningococcal isolates with a cnl belonged to one of four otherwise
      genetically diverse genetic groupings: the ST-53 and ST-1117 complexes (75
      isolates); the ST-845 complex (12 isolates); the ST-198 and 1136 complexes (46
      isolates), and the ST-44 complex (one isolate). These data demonstrated that a
      substantial proportion of carried meningococci were incapable of capsule
      production, that the cnl circulated within Neisseria populations by horizontal
      genetic exchange, and that the expression of a polysaccharide capsule was not a
      requirement for person-to-person transmission of certain meningococcal lineages.

PMID- 12055303
TI  - Genetic diversity of three lgt loci for biosynthesis of lipooligosaccharide (LOS)
      in Neisseria species.
AB  - Lipooligosaccharide (LOS) is a major virulence factor of the pathogenic
      Neisseria. Nine lgt genes at three chromosomal loci (lgt-1, 2, 3) encoding the
      glycosyltransferases responsible for the biosynthesis of LOS oligosaccharide
      chains were examined in 26 Neisseria meningitidis, 51 Neisseria gonorrhoeae and
      18 commensal Neisseria strains. DNA hybridization, PCR and nucleotide sequence
      data were compared to previously reported lgt genes. Analysis of the genetic
      organization of the lgt loci revealed that in N. meningitidis, the lgt-1 and lgt
      3 loci were hypervariable genomic regions, whereas the lgt-2 locus was conserved.
      In N. gonorrhoeae, no variability in the composition or organization of the three
      lgt loci was observed. lgt genes were detected only in some commensal Neisseria
      species. The genetic organization of the lgt-1 locus was classified into eight
      types and the lgt-3 locus was classified into four types. Two types of
      arrangement at lgt-1 (II and IV) and one type of arrangement at lgt-3 (IV) were
      novel genetic organizations reported in this study. Based on the three lgt loci,
      10 LOS genotypes of N. meningitidis were distinguished. Phylogenetic analysis
      revealed a gene cluster, lgtH, which separated from the homologous genes lgtB and
      lgtE. The lgtH and lgtE genes were mutually exclusive and were located at the
      same position in lgt-1. The data demonstrated that pathogenic and commensal
      Neisseria share a common lgt gene pool and horizontal gene transfer appears to
      contribute to the genetic diversity of the lgt loci in Neisseria.

PMID- 12055302
TI  - Differential cross-complementation patterns of Escherichia coli and Neisseria
      gonorrhoeae RecA proteins.
AB  - The Escherichia coli RecA protein is one of the best-studied enzymes, but less is
      understood about how RecA homologues of other species are similar to or different
      from the E. coli RecA. In the Gram-negative pathogen Neisseria gonorrhoeae (the
      gonococcus; Gc), the causative agent of gonorrhoea, RecA is involved in DNA
      transformation, pilin antigenic variation, and DNA repair. By expressing the recA
      genes from Gc and E. coli under control of lac regulatory sequences in E. coli,
      the authors have shown that the Gc RecA fully complements an E. coli recA mutant
      for homologous recombination, but only partially complements for survival to DNA
      damage. By expressing similar constructs in Gc, it was shown that the E. coli
      RecA complements for pilin antigenic variation, partially complements for DNA
      transformation, but does not complement for survival to DNA damage, suggesting
      that species-specific interactions are important for DNA repair, but not for
      homologous recombination. Co-expression of the E. coli recA and recX genes in Gc
      suggests that in this heterologous system RecX modulates RecA-mediated processes.

PMID- 12055304
TI  - Isolation and characterization of 14 additional genes specifying the anaerobic
      biosynthesis of cobalamin (vitamin B12) in Propionibacterium freudenreichii (P.
      shermanii).
AB  - A search for genes encoding enzymes involved in cobalamin (vitamin B12)
      production in the commercially important organism Propionibacterium
      freudenreichii (P. shermanii) has resulted in the isolation of an additional 14
      genes encoding enzymes responsible for 17 steps of the anaerobic B12 pathway in
      this organism. All of the genes believed to be necessary for the biosynthesis of
      adenosylcobinamide from uroporphyrinogen III have now been isolated except two
      (cbiA and an as yet unidentified gene encoding cobalt reductase). Most of the
      genes are contained in two divergent operons, one of which, in turn, is closely
      linked to the operon encoding the B12-dependent enzyme methylmalonyl-CoA mutase.
      The close linkage of the three genes encoding the subunits of transcarboxylase to
      the hemYHBXRL gene cluster is reported. The functions of the P. freudenreichii
      B12 pathway genes are discussed, and a mechanism for the regulation of cobalamin
      and propionic acid production by oxygen in this organism is proposed.

PMID- 12055305
TI  - Assessment of the pathogenic potential of two Listeria monocytogenes human faecal
      carriage isolates.
AB  - Two human faeces carriage isolates of Listeria monocytogenes (H1 and H2) were
      compared to reference strains (ScottA and LO28) with regard to their lethality in
      14-day-old chick embryos, their haemolytic and phospholipase (phosphatidylcholine
      phospholipase C and phosphatidylinositol-phospholipase C) activities and their
      invasiveness towards Caco-2 cells. Experimental infection of chick embryos
      allowed discrimination of the strains into those exhibiting high virulence
      (ScottA and H2), those exhibiting slightly attenuated virulence (LO28) and those
      exhibiting low virulence (H1). A similar percentage mortality and time to death
      for embryos was observed when they were infected with H2 as was seen with
      infection by the reference strain ScottA. Therefore, human carriage strain H2 was
      considered potentially pathogenic. In contrast to H2 and ScottA, H1 exhibited low
      virulence. Using the tissue-culture cell-line model, it was found that carriage
      strain H1 was unable to enter Caco-2 cells efficiently, even though it was
      similar to the virulent strains in terms of the enzymic activities involved in
      pathogenicity. Detection of the internalins InlA and InlB, involved in the
      internalization of L. monocytogenes in the host cells, by immunoblot indicated
      that a truncated form of InlA was produced by H1. Taken together, these data
      provide a starting point for the study of the behaviour of two types of human
      faeces carriage strains and their characterization.

PMID- 12055306
TI  - Enterococcus faecalis surface proteins determine its adhesion mechanism to bile
      drain materials.
AB  - An important step in infections associated with biliary drains is adhesion of
      micro-organisms to the surface. In this study the role of three surface proteins
      of Enterococcus faecalis (enterococcal surface protein, aggregation substances 1
      and 373) in the adhesion to silicone rubber, fluoro-ethylene-propylene and
      polyethylene was examined. Four isogenic E. faecalis strains with and without
      aggregation substances and one strain expressing enterococcal surface protein
      were used. The kinetics of enterococcal adhesion to the materials was measured in
      situ in a parallel plate flow chamber. Initial deposition rates were similar for
      all strains, whereas the presence of surface proteins increased the total number
      of adhering bacteria. Nearest neighbour analysis demonstrated that enterococci
      expressing the whole sex-pheromone plasmid encoding aggregation substances 1 or
      373 adhered in higher numbers through mechanisms of positive cooperativity, which
      means that adhesion of bacteria enhances the probability of adhesion of other
      bacteria near these bacteria. Enterococci with the enterococcal surface protein
      did not adhere through this mechanism. These findings indicate that the surface
      proteins of E. faecalis play a key role in the adhesion to bile drains and bile
      drain associated infections.

PMID- 12055307
TI  - Adhesion to cellulose of the Gram-positive bacterium Ruminococcus albus involves
      type IV pili.
AB  - This study was aimed at characterizing a cell-surface 25 kDa glycoprotein (GP25)
      that was previously shown to be underproduced by a spontaneous adhesion-defective
      mutant D5 of Ruminococcus albus 20. An antiserum against wild-type strain 20 was
      adsorbed with the mutant D5 to enrich it in antibodies 'specific' to adhesion
      structures of R. albus 20. The resulting antiserum, called anti-Adh serum,
      blocked adhesion of R. albus 20 and reacted mainly with GP25 in bacterial and
      extracellular protein fractions of R. albus 20. The N-terminal sequence of
      purified GP25 was identical to that of CbpC, a 21 kDa cellulose-binding protein
      (CBP) of R. albus 8. The nucleotide sequence of the gp25 gene was determined by
      PCR and genomic walking procedures. The gp25 gene encoded a protein of 165 aa
      with a calculated molecular mass of 16940 Da that showed 72.9% identity with CbpC
      and presented homologies with type IV pilins of Gram-negative pathogenic
      bacteria. Negative-staining electron microscopy revealed fine and flexible pili
      surrounding R. albus 20 cells while mutant cells were not piliated. In addition,
      immunoelectron microscopy showed that the anti-Adh serum probing mainly GP25,
      completely decorated the pili surrounding R. albus 20, thereby showing that GP25
      was a major pilus subunit. This study shows for the first time the presence of
      pili at the surface of R. albus and identifies GP25 as their major protein
      subunit. Though GP25 was not identified as a CBP, isolated pili were shown to
      bind cellulose. In conclusion, these pili, which belong to the family of type IV
      pili, mediate adhesion of R. albus 20 to cellulose.

PMID- 12055308
TI  - Location of functional groups in mycobacterial meromycolate chains; the
      recognition of new structural principles in mycolic acids.
AB  - Mycobacterial alpha-, methoxy- and keto-mycolic acid methyl esters were separated
      by argentation chromatography into mycolates with no double bond, with one trans
      double bond or with one cis double bond. Meromycolic acids were prepared from
      each methyl mycolate fraction by pyrolysis, followed by silver oxide oxidation,
      and analysed by high-energy collision-induced dissociation/fast atom bombardment
      MS to reveal the exact locations of the functional groups within the meromycolate
      chain. The locations of cis and trans double bonds, cis and trans cyclopropane
      rings, methoxy and keto groups, and methyl branches within the meromycolate chain
      were determined from their characteristic fragment ion profiles, and the
      structures of the meromycolic acids, including those with three functional groups
      extracted from Mycobacterium tuberculosis H37Ra, Mycobacterium bovis BCG and
      Mycobacterium microti, were established. Meromycolic acids with one cis double
      bond were structurally closely related to those with one cis cyclopropane ring,
      whereas the meromycolic acids with one trans cyclopropane ring were closely
      related to the corresponding meromycolic acids with one cis cyclopropane ring. A
      close relationship between methoxy- and keto-meromycolic acids was also implied.
      The relationship between the meromycolic acids with a trans double bond and the
      other meromycolic acids was not clearly revealed, and they did not appear to be
      immediate substrates for trans cyclopropanation.

PMID- 12055309
TI  - Structure and regulation of the omega-3 polyunsaturated fatty acid synthase genes
      from the deep-sea bacterium Photobacterium profundum strain SS9.
AB  - Omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (20:5n
      3; EPA) and docosahexaenoic acid (22:6n-3; DHA) have been shown to be of major
      importance in the promotion of cardiovascular health, proper human development
      and the prevention of some cancers. A high proportion of bacterial isolates from
      low-temperature and high-pressure marine environments produce EPA or DHA. This
      paper presents the sequence of a 33 kbp locus from the deep-sea bacterium
      Photobacterium profundum strain SS9 which includes four of the five genes
      required for EPA biosynthesis. As with other bacterial pfa (polyunsaturated fatty
      acid) genes, the deduced amino acid sequences encoded by the SS9 genes reveal
      large multidomain proteins that are likely to catalyse EPA biosynthesis by a
      novel polyketide synthesis mechanism. RNase protection experiments separated the
      SS9 pfa genes into two transcriptional units, pfaA-C and pfaD. The pfaA
      transcriptional start site was identified. Cultivation at elevated hydrostatic
      pressure or reduced temperature did not increase pfa gene expression despite the
      resulting increase in percentage composition of EPA under these conditions.
      However, a regulatory mutant was characterized which showed both increased
      expression of pfaA-D and elevated EPA percentage composition. This result
      suggests that a regulatory factor exists which coordinates pfaA-D transcription.
      Additional consideration regarding the activities required for PUFA synthesis is
      provided together with comparative analyses of bacterial pfa genes and gene
      products.

PMID- 12055310
TI  - Dichloromethane metabolism and C1 utilization genes in Methylobacterium strains.
AB  - The ability of methylotrophic alpha-proteobacteria to grow with dichloromethane
      (DCM) as source of carbon and energy has long been thought to depend solely on a
      single cytoplasmic enzyme, DCM dehalogenase, which converts DCM to formaldehyde,
      a central intermediate of methylotrophic growth. The gene dcmA encoding DCM
      dehalogenase of Methylobacterium dichloromethanicum DM4 was expressed from a
      plasmid in closely related Methylobacterium strains lacking this enzyme. The
      ability to grow with DCM could be conferred upon Methylobacterium
      chloromethanicum CM4, a chloromethane degrader, but not upon Methylobacterium
      extorquens AM1. In addition, growth of strain AM1 with methanol was impaired in
      the presence of DCM. The possibility that single-carbon (C1) utilization pathways
      in dehalogenating Methylobacterium strains differed from those discovered in
      strain AM1 was addressed. Homologues of tetrahydrofolate-linked and
      tetrahydromethanopterin-linked C1 utilization genes of strain AM1 were detected
      in both strain DM4 and strain CM4, and cloning and sequencing of several of these
      genes from strain DM4 revealed very high sequence identity (96.5-99.7%) to the
      corresponding genes of strain AM1. The expression of transcriptional xylE fusions
      of selected genes of the tetrahydrofolate- and tetrahydromethanopterin-linked
      pathways from strain DM4 was investigated. The data obtained suggest that the
      expression levels of some C1 utilization genes in M. dichloromethanicum DM4 grown
      with DCM may differ from those observed during growth with methanol.

PMID- 12055311
TI  - Evolutionary relationship of phototrophic bacteria in the alpha-Proteobacteria
      based on farnesyl diphosphate synthase.
AB  - Partial sequences of farnesyl diphosphate (FPP) synthase genes derived from the
      Rhodobacter-Rhodovulum group and from the Rhodopseudomonas palustris
      Bradyrhizobium japonicum group of the alpha-Proteobacteria were subjected to
      phylogenetic analysis to investigate the relationships of phototrophic and non
      phototrophic bacteria in the alpha-Proteobacteria . The four Rhodovulum species
      formed a monophyletic group within the Rhodobacter cluster, and Agrobacterium
      ferrugineum IAM 12616(T) intermingled with the Rhodobacter species. This topology
      is in good agreement with the 16S rRNA phylogeny, although the FPP synthase gene
      was more divergent than the 16S rRNA. On the other hand, strains of the
      phototrophic Rps. palustris formed a cluster far from that of the non
      phototrophic Bradyrhizobium japonicum strains. Moreover, Rps. palustris strains
      were differentiated from the nodule-forming B. japonicum, Mezorhizobium loti MAFF
      303099 and Sinorhizobium sp. NGR 234 in the FPP synthase phylogeny. This
      relationship does not agree with the 16S rRNA phylogeny, wherein Rps. palustris
      was more closely related to B. japonicum than to strains of the Rhodobacter
      Rhodovulum group. These results suggest that the FPP synthase gene of Rps.
      palustris diverged from that of B. japonicum.

PMID- 12055312
TI  - The lon gene, encoding an ATP-dependent protease, is a novel member of the
      HAIR/HspR stress-response regulon in actinomycetes.
AB  - Members of a family of ATP-dependent proteases related to Lon from Escherichia
      coli are present in most prokaryotes and eukaryotes. These proteases are
      generally reported to be heat induced, and various regulatory systems have been
      described. The authors cloned and disrupted the lon gene and studied the
      regulation of its expression in Streptomyces lividans. lon is negatively
      regulated by the HspR/HAIR repressor/operator system, suggesting that Lon is
      produced concomitantly with the other members of this regulon, DnaK and ClpB. The
      lon mutant grew more slowly than the wild-type and spore germination was impaired
      at high temperature. Nevertheless its cell cycle was not greatly affected and it
      sporulated normally.

PMID- 12055313
TI  - Mineralization of aromatic compounds by brown-rot basidiomycetes - mechanisms
      involved in initial attack on the aromatic ring.
AB  - Benzaldehyde and its metabolic intermediates were effectively degraded by the
      brown-rot basidiomycetes Tyromyces palustris and Gloeophyllum trabeum. The
      pathway of benzaldehyde degradation was elucidated by the identification of
      fungal metabolites produced upon the addition of benzaldehyde and its metabolic
      intermediates. The oxidation and reduction occurred simultaneously, forming
      benzyl alcohol and benzoic acid as major products. Hydroxylation reactions, which
      seemed to be a key step, occurred on benzaldehyde and benzoic acid, but not on
      benzyl alcohol, to form corresponding 4-hydroxyl and 3,4-dihydroxyl derivatives.
      1-Formyl derivatives were oxidized to 1-carboxyl derivatives at several metabolic
      stages. All of these reactions resulted in the formation of 3,4-dihydroxybenzoic
      acid. This was further metabolized via the decarboxylation reaction to yield
      1,2,4-trihydroxybenzene, which may be susceptible to the ring-fission reaction.
      Ring-U-14C-labelled benzaldehyde and benzoic acid were effectively mineralized,
      clearly indicating that the brown-rot basidiomycetes are capable of metabolizing
      certain aromatic compounds to CO2 and H2O, despite the fact that brown-rot fungi
      cannot degrade polymeric lignin. Inhibitor experiments, using hydroxyl radical
      scavengers, catalase and cytochrome P450 inhibitors, strongly suggested that the
      aromatic hydroxylation reactions found in the brown-rot fungi are catalysed by
      intracellular enzyme(s), but not by Fenton-reaction-derived hydroxyl radicals.

PMID- 12055314
TI  - Molecular characterization and endosymbiotic localization of the gene encoding D
      ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) form II in the deep-sea
      vestimentiferan trophosome.
AB  - To better understand the contribution of micro-organisms to the primary
      production in the deep-sea gutless tubeworm Lamellibrachia sp., the 16S-rDNA
      based phylogenetic data would be complemented by knowledge of the genes that
      encode the enzymes relevant to chemoautotrophic carbon fixation, such as D
      ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO; EC 4.1.1.39). To
      phylogenetically characterize the autotrophic endosymbiosis within the trophosome
      of the tubeworm Lamellibrachia sp., bulk trophosomal DNA was extracted and
      analysed based on the 16S-rRNA- and RuBisCO-encoding genes. The 16S-rRNA- and
      RuBisCO-encoding genes were amplified by PCR, cloned and sequenced. For the 16S
      rDNA, a total of 50 clones were randomly selected and analysed directly by
      sequencing. Only one operational taxonomic unit resulted from the 16S rDNA
      sequence analysis. This may indicate the occurrence of one endosymbiotic
      bacterial species within the trophosome of the Lamellibrachia sp. used in this
      study. Phylogenetic analysis of the 16S rDNA showed that the Lamellibrachia sp.
      endosymbiont was closely related to the genus Rhodobacter, a member of the alpha
      Protebacteria. For the RuBisCO genes, only the form II gene (cbbM) was amplified
      by PCR. A total of 50 cbbM clones were sequenced, and these were grouped into two
      operational RuBisCO units (ORUs) based on their deduced amino acid sequences. The
      cbbM ORUs showed high amino acid identities with those recorded from the ambient
      sediment bacteria. To confirm the results of sequence analysis, the localization
      of the symbiont-specific 16S rRNA and cbbM sequences in the Lamellibrachia sp.
      trophosome was visualized by in situ hybridization (ISH), using specific probes.
      Two types of cells, coccoid and filamentous, were observed at the peripheries of
      the trophosome lobules. Both the symbiont-specific 16S rDNA and cbbM probes
      hybridized at the same sites coincident with the location of the coccoid cells,
      whereas the filamentous cells showed no cbbM-specific signals. The RuBisCO form I
      gene (cbbL) was neither amplified by PCR nor detected by ISH. This is the first
      demonstration of chemoautotrophic symbiosis in the deep-sea gutless tubeworm,
      based on sequence data and in situ localization of both the 16S-rRNA- and RuBisCO
      encoding genes.

PMID- 12055315
TI  - Reassessment of major products of N2 fixation by bacteroids from soybean root
      nodules.
AB  - NH3/ was the principal product from soybean bacteroids, prepared by various
      procedures, when assayed in solution in a flow chamber under N2 fixation
      conditions. In addition, small quantities of alanine were produced (reaching 20%
      of NH3/ under some conditions). Some 15N was assimilated by bacteroids purified
      from soybean root nodules on Percoll density gradients and shaken with 15N2 and
      0.008 atm O2. Under these conditions, accounted for 93% of the (15)N fixed into
      the soluble fraction. This fraction contained no measurable [15N]alanine. Neither
      these bacteroids nor those prepared by the previously used differential
      centrifugation method, when incubated with exogenous alanine under non-N2-fixing
      conditions, gave rise to NH3 from alanine. Therefore, contamination of bacteroid
      preparations with enzymes of plant cytosolic origin and capable of producing NH3
      from alanine cannot explain the failure to detect [15N]alanine [as reported
      elsewhere: Waters, J. K., Hughes, B. L., II, Purcell, L. C., Gerhardt, K. O.,
      Mawhinney, T. P. & Emerich, D. W. (1998). Proc Natl Acad Sci USA 95, 12038
      12042]. Cell-free extracts of the bacteroids as used in the 15N experiments
      contained alanine dehydrogenase and were able to produce alanine from pyruvate
      and. Other experiments with alanine dehydrogenase in extracts of cultured
      rhizobia and bacteroids are reported and discussed in relation to the 15N
      experiments. Possible reasons for the differences between laboratories regarding
      the role of alanine are discussed. It is concluded that NH3 is the principal
      soluble product of N2 fixation by suspensions of soybean bacteroids ex planta and
      that should continue to be considered the principal product of N2 fixation which
      is assimilated in vivo in soybean nodules.

PMID- 12055316
TI  - The relation of body mass index, cardiorespiratory fitness, and all-cause
      mortality in women.
AB  - OBJECTIVE: To examine the relation of body mass index (BMI), cardiorespiratory
      fitness (CRF), and all-cause mortality in women. RESEARCH METHODS AND PROCEDURES:
      A cohort of women (42.9 +/- 10.4 years) was assessed for CRF, height, and weight.
      Participants were divided into three BMI categories (normal, overweight, and
      obese) and three CRF categories (low, moderate, and high). After adjustment for
      age, smoking, and baseline health status, the relative risk (RR) of all-cause
      mortality was determined for each group. Further multivariate analyses were
      performed to examine the contribution of each predictor (e.g., age, BMI, CRF,
      smoking status, and baseline health status) on all-cause mortality while
      controlling for all other predictors. RESULTS: During follow-up (113,145 woman
      years), 195 deaths from all causes occurred. Compared with normal weight (RR =
      1.0), overweight (RR = 0.92) and obesity (RR = 1.58) did not significantly
      increase all-cause mortality risk. Compared with low CRF (RR = 1.0), moderate (RR
      = 0.48) and high (RR = 0.57) CRF were associated significantly with lower
      mortality risk (p = 0.002). In multivariate analyses, moderate (RR = 0.49) and
      high (RR = 0.57) CRF were strongly associated with decreased mortality relative
      to low CRF (p = 0.003). Compared with normal weight (RR = 1.0), overweight (RR =
      0.84) and obesity (RR = 1.21) were not significantly associated with all-cause
      mortality. DISCUSSION: Low CRF in women was an important predictor of all-cause
      mortality. BMI, as a predictor of all-cause mortality risk in women, may be
      misleading unless CRF is also considered.

PMID- 12055317
TI  - Fat distribution and insulin sensitivity in postmenopausal women: influence of
      hormone replacement.
AB  - OBJECTIVE: To examine cross-sectionally the influence of hormone replacement
      therapy (HRT) on the relationship between body composition and insulin
      sensitivity (Si). RESEARCH METHODS AND PROCEDURES: Subjects were 57 early
      postmenopausal white women, 33 receiving HRT and 24 controls. Body composition
      was estimated using DXA and computed tomography scans at the abdomen and mid
      thigh. Si was assessed by a frequently sampled intravenous glucose tolerance test
      with minimal model analysis. RESULTS: Compared with nonusers, HRT users had lower
      visceral adipose tissue, fasting serum glucose, and fasting insulin. Total body
      fat and unadjusted Si did not differ between groups. Visceral adipose tissue mass
      (VATM) was the only body-fat compartment significantly associated with Si (r(2) =
      0.43, p < 0.0001) in a model including total-body fat, upper-trunk fat,
      subcutaneous abdominal fat mass, leg fat, and mid-thigh low-density lean tissue.
      Lean body mass was positively correlated with Si among HRT users and tended to be
      negatively correlated among nonusers. HRT status also affected the relationship
      between VATM and Si such that, relative to nonusers, HRT users had lower Si
      across lower VATM levels, but higher Si across higher VATM. DISCUSSION: These
      results suggest that in postmenopausal women, VATM is uniquely related to Si. HRT
      affects the relationship between VATM and Si and between lean body mass and Si.
      These interactions should be considered in future studies.

PMID- 12055318
TI  - Effect of protein intake on bone mineralization during weight loss: a 6-month
      trial.
AB  - OBJECTIVE: The long-term effect of dietary protein on bone mineralization is not
      well understood. RESEARCH METHODS AND PROCEDURES: Sixty-five overweight (body
      mass index, 25 to 29.9 kg/m(2)) or obese (> or =30 kg/m(2)) subjects were
      enrolled in a randomized, placebo-controlled, 6-month dietary-intervention study
      comparing two controlled ad libitum diets with matched fat contents: high protein
      (HP) or low protein (LP). Body composition was assessed by DXA. RESULTS: In the
      HP group, dietary-protein intake increased from 91.4 g/d to a 6-month
      intervention mean of 107.8 g/d (p < 0.05) and decreased in the LP group from 91.1
      g/d to 70.4 g/d (p < 0.05). Total weight loss after 6 months was 8.9 kg in the HP
      group, 5.1 kg in the LP group, and none in the control group. After 6 months,
      bone mineral content (BMC) had declined by 111 +/- 13 g (4%) in the HP group and
      by 85 +/- 13 g (3%) in the LP group (not significant). Loss of BMC was more
      positively correlated with loss of body fat mass (r = 0.83; p < 0.0001) than with
      loss of body weight. Six-month BMC loss, adjusted for differences in fat loss,
      was greater in the LP group than in the HP group [difference in LP vs. HP, 44.8 g
      (95% confidence interval, 16 to 73.8 g); p < 0.05]. Independent of change in body
      weight and composition during the intervention, highprotein intake was associated
      with a diminished loss of BMC (p < 0.01). DISCUSSION: Body-fat loss was the major
      determinant of loss of BMC, and we found no adverse effects of 6 months of high
      protein intake on BMC.

PMID- 12055319
TI  - Increased serum cholesteryl ester transfer protein in obese children.
AB  - OBJECTIVE: To determine whether serum cholesteryl ester transfer protein (CETP),
      which is one of the physiologically active gene products secreted from adipose
      tissue, is increased and associated with atherogenic lipoprotein profile in obese
      children. RESEARCH METHODS AND PROCEDURES: Subjects were 42 consecutive
      outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5
      to 14 years, and 25 age-matched non-obese children, 13 boys and 12 girls, as the
      control group for measuring CETP mass. Blood was drawn after an overnight fast
      and, at the same time, and anthropometric measurements including height, body
      weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses
      were taken. Paired samples were obtained from 15 obese children who underwent
      psychoeducational therapy. Serum CETP mass was assayed by an enzyme-linked
      immunosorbent assay. RESULTS: The serum levels of triglyceride, total cholesterol
      (TC), low-density lipoprotein cholesterol, TC/high-density lipoprotein
      cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A(1), and insulin in obese
      children were significantly higher than the respective reference values. Serum
      CETP level was approximately 2-fold higher (98.7 +/- 3.6 vs. 50.9 +/- 4.0 nM,
      means +/- SEM, p < 0.001) in the obese children than in the controls. In 15 obese
      children, whose percentage of overweight declined during therapy, CETP levels
      decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and
      insulin, and with percentage of overweight when the data of the obese and non
      obese children were combined. DISCUSSION: CETP is increased and associated with
      the atherogenic lipoprotein profile in obese children.

PMID- 12055320
TI  - Body mass index-related human adipocyte agouti expression is sex-specific but not
      depot-specific.
AB  - OBJECTIVE: To determine if human adipocyte agouti signal protein (ASIP) mRNA
      expression is associated with obesity and is gender and/or depot specific.
      RESEARCH METHODS AND PROCEDURES: Subjects included 8 men (64 +/- 3 years) and 14
      women (56 +/- 15 years) undergoing elective abdominal surgery. ASIP mRNA levels
      in isolated omental and subcutaneous abdominal adipocytes were measured by
      quantitative reverse transcription polymerase chain reaction. RESULTS: No
      significant depot difference was observed between genders; ASIP mRNA levels of
      omental and subcutaneous abdominal adipocytes were pooled for this analysis. BMI
      and ASIP gene expression were negatively correlated in men (rho = -0.70; p <
      0.05), whereas a positive relationship was observed in women (rho = 0.48; p <
      0.05). No significant difference was observed in age, body weight, body mass
      index (BMI), and waist circumference between groups. Hip circumference was
      significantly higher in women than in men (p < 0.05). Also, no significant
      difference in ASIP mRNA expression was observed between men and women, regardless
      of the fat depot. DISCUSSION: These results show that men and women of similar
      age and BMI present similar ASIP mRNA levels in omental and subcutaneous
      abdominal adipocytes. However, a sexual dimorphism exists in the relationship
      between ASIP expression and BMI. If ASIP is involved in appetite regulation or
      energy homeostasis in humans, this observation may contribute to the recognized
      differences in these parameters between men and women.

PMID- 12055321
TI  - Parental feeding style and the inter-generational transmission of obesity risk.
AB  - OBJECTIVE: This study was designed to determine whether a community sample of
      obese mothers with young children used different feeding styles compared with a
      matched sample of normal-weight mothers. Four aspects of feeding style were
      assessed: emotional feeding, instrumental feeding (using food as a reward),
      prompting/encouragement to eat, and control over eating. RESEARCH METHODS AND
      PROCEDURES: Participants were from 214 families with same-sex twins; 100 families
      in which both parents were overweight or obese and 114 in which both parents were
      normal weight or lean. RESULTS: We found that obese mothers were no more likely
      than normal-weight mothers to offer food to deal with emotional distress, use
      food as a form of reward, or encourage the child to eat more than was wanted. The
      obese and normal-weight mothers did differ on "control"; obese mothers reported
      significantly less control over their children's intake, and this was seen for
      both first-born and second-born twins. Twin analyses showed that these
      differences were not in response to children's genetic propensities, because
      monozygotic correlations were no greater than dizygotic correlations for maternal
      feeding style. DISCUSSION: These results suggest that the stereotype of the obese
      mother, who uses food in nonnutritive ways so that her child also becomes obese,
      is more likely to be myth than fact. However, the results raise the possibility
      that lack of control of food intake might contribute to the emergence of
      differences in weight.

PMID- 12055322
TI  - A genealogical study of essential hypertension with and without obesity in French
      Canadians.
AB  - OBJECTIVES: To investigate genetic homogeneity in a set of hypertensive families
      and in subsets chosen for high and low prevalence of obesity; and to compare
      fasting insulin and lipids, ion transport, and water homeostasis in the obese and
      lean families. RESEARCH METHODS AND PROCEDURES: The study was carried out in a
      relative population isolate of the Saguenay/Lac St. Jean region in Canada.
      Genetic homogeneity was evaluated with the mean coeffigcients of kinship (phi)
      and inbreeding (F) computed with ascending genealogies. Serum insulin and lipids
      were measured after overnight fasting. Total body water was estimated with
      bioelectrical impedance. Sodium-lithium countertransport and sodium-potassium co
      transport were determined in freshly isolated erythrocytes. RESULTS: F and phi
      were increased in hypertensive families compared with families selected at
      random. F and phi were further increased within the subsets of obese and lean
      families. In addition, fasting insulin, total body water, sodium-lithium
      countertransport, and sodium-potassium co-transport were higher in the obese than
      in the lean families. The two subsets of families did not differ by fasting
      lipids. DISCUSSION: In the Saguenay/Lac St. Jean population, the degree of
      genetic homogeneity was increased in families selected for hypertension, and it
      was further increased in subsets of hypertensive families with high and low
      prevalence of obesity. This suggests that hypertension in lean and obese
      individuals may represent, at least in part, separate genetic entities. Some of
      the extra genes shared in common within the subsets may contribute to their
      differences in body weight, insulin sensitivity, ion transport, and water
      homeostasis.

PMID- 12055323
TI  - Impact of interviewer's body mass index on underreporting energy intake in
      overweight and obese women.
AB  - OBJECTIVE: To determine if overweight and obese women provide more accurate
      reports of their energy intake by 1) in-person recall with an obese interviewer,
      2) in-person recall with a lean interviewer, or 3) telephone recall with an
      unknown interviewer. RESEARCH METHODS AND PROCEDURES: Eighty-eight overweight and
      obese women participated in this study. Subjects completed one telephone
      administered multiple-pass 24-hour recall (MP24R) with an unknown interviewer and
      were then randomly assigned to an in-person MP24R with either a lean or obese
      interviewer to gather reported energy intake (rEI). Basal metabolic rate (BMR)
      was measured using a Deltrac monitor, and physical activity (EEPA) was estimated
      using a Caltrac accelerometer. Therefore, estimated energy expenditure was
      determined by: estTEE = (BMR + EEPA) x 1.10. RESULTS: No significant differences
      were found between the two in-person interview modes for subject age, weight,
      body mass index, percentage of body fat, total energy expenditure, rEI, and
      misreporting of energy intake. In-person recall data were combined for comparison
      with the telephone recalls. No significant difference was found between the in
      person and telephone recalls for rEI and misreporting. Mean reported energy
      intake was significantly lower than estimated total energy expenditure for the
      telephone recalls and combined (lean and obese modes) in-person recalls.
      CONCLUSIONS: This study found that interviewer body mass index had no impact on
      self-reported energy intake during an in-person MP24R, and that telephone recall
      data were comparable with in-person recalls. Underreporting was a widespread
      problem ( approximately 26%) for all modes in this sample.

PMID- 12055324
TI  - Evidence that intermittent, excessive sugar intake causes endogenous opioid
      dependence.
AB  - OBJECTIVE: The goal was to determine whether withdrawal from sugar can cause
      signs of opioid dependence. Because palatable food stimulates neural systems that
      are implicated in drug addiction, it was hypothesized that intermittent,
      excessive sugar intake might create dependency, as indicated by withdrawal signs.
      RESEARCH METHODS AND PROCEDURES: Male rats were food-deprived for 12 hours daily,
      including 4 hours in the early dark, and then offered highly palatable 25%
      glucose in addition to chow for the next 12 hours. Withdrawal was induced by
      naloxone or food deprivation. Withdrawal signs were measured by observation,
      ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis.
      RESULTS: Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as
      teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours
      caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg
      subcutaneously) caused reduced time on the exposed arm of an elevated plus maze,
      where again significant teeth chattering was recorded. The plus maze anxiety
      effect was replicated with four control groups for comparison. Accumbens
      microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally)
      decreased extracellular dopamine (DA), while dose-dependently increasing
      acetylcholine (ACh). The naloxone-induced DA/ACh imbalance was replicated with
      10% sucrose and 3 mg/kg naloxone subcutaneously. DISCUSSION: Repeated, excessive
      intake of sugar created a state in which an opioid antagonist caused behavioral
      and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh
      imbalance were qualitatively similar to withdrawal from morphine or nicotine,
      suggesting that the rats had become sugar-dependent.

PMID- 12055325
TI  - Echocardiographic abnormalities in normotensive obese patients: relationship with
      visceral fat.
AB  - OBJECTIVE: To evaluate the relationship of echocardiographic characteristics and
      visceral adipose tissue (VAT) distribution in normotensive obese patients.
      RESEARCH METHODS AND PROCEDURES: Echocardiographic parameters were assessed in 28
      normotensive obese patients [7 men, 21 women, mean age, 43.2 years; mean body
      mass index (BMI), 37.2 kg/m(2); 10 with impaired glucose tolerance (IGT); 6 with
      type 2 diabetes] and 18 sex- and age-matched healthy, normal-weight controls (4
      men, 14 women; mean age, 45.8 years; mean BMI, 22.4 kg/m(2)) by an M-mode, color
      doppler videofluoroscope. VAT in the obese patients was assessed by computed
      tomography (at L4 level). RESULTS: The obese patients had a significantly larger
      internal diastolic left ventricular (LV) diameter (p < 0.05), a thicker end
      diastolic septum (p < 0.001) and posterior wall (p < 0.001), a greater indexed
      (g/m(2.7)) LV mass (p < 0.001), a higher atrial diastolic filling wave velocity
      (p < 0.001), a lower ratio between early and atrial diastolic filling wave
      velocities (p < 0.01), and a prolonged isovolumic relaxation time (p < 0.05). End
      diastolic septum and posterior wall thickness and the LV mass were significantly
      greater in patients with a VAT area >130 cm(2) than with <130 cm(2). In the
      multivariate regression analysis, only VAT (p < 0.0001), waist-to-hip ratio (p <
      0.001), and sex (p < 0.001) were associated with the most important
      echocardiographic alterations. DISCUSSION: The morphological and functional
      echocardiographic alterations usually found in normotensive obese patients
      closely correlate with the amount of intra-abdominal fat deposition, even in the
      presence of diabetes or IGT.

PMID- 12055326
TI  - Opposite regulation of interleukin-8 and tumor necrosis factor-alpha by weight
      loss.
AB  - OBJECTIVE: To obtain more information on the possible influence of body mass
      index (BMI) and weight loss on interleukin-8 (IL-8) in plasma and in the adipose
      tissue. Tumor necrosis factor-alpha (TNF-alpha) was used for comparison and
      determined in parallel with IL-8. RESEARCH METHODS AND PROCEDURES: The study was
      divided into three parts: 1) a cross-sectional study that included 89 subjects;
      2) a 20-week intervention study in which 34 healthy obese subjects received a
      dietary intervention for 8 weeks followed by an additional 12 weeks on a weight
      stabilization diet; 3) from this latter study, a subgroup of 8 obese subjects was
      investigated with a subcutaneous adipose-tissue biopsy. RESULTS: In the cross
      sectional study, plasma levels of TNF-alpha (p < 0.01), but not IL-8, was
      correlated with BMI. However, in a subgroup (BMI, 20 to 30 kg/m(2)), IL-8 was
      correlated with BMI (p < 0.01). In the intervention study, weight loss and weight
      maintenance led to an increase in IL-8 by 30% (p < 0.05) and a decrease in TNF
      alpha by 40% (p < 0.001), which were paralleled in the adipose tissue,
      demonstrating a 2- to 3-fold increase (p < 0.01) and a 40% to 80% decrease (p <
      0.01) in IL-8 and TNF-alpha, respectively. DISCUSSION: Weight loss in obese
      subjects was associated with opposite changes in the secretion and transcription
      of IL-8 and TNF-alpha in the adipose tissue, as well as in plasma. This could
      indicate that plasma IL-8 under some conditions may be related to changes in
      adipose tissue IL-8 production.

PMID- 12055327
TI  - Familial resemblance of 7-year changes in body mass and adiposity.
AB  - OBJECTIVE: To investigate the familial resemblance of 7-year changes in body mass
      and adiposity among Canadian families. RESEARCH METHODS AND PROCEDURES: The
      sample consisted of 655 women and 660 men from 521 families who participated in
      the Canada Fitness Survey in 1981 and the follow-up Campbell's Survey in 1988.
      Indicators of baseline and 7-year changes in body mass and adiposity included
      body mass (kilograms), body mass index (BMI; kilograms per square meter), sum of
      five skinfolds (SF5; millimeters), and waist circumference (WC; millimeters). The
      data were adjusted for the effects of age and sex, and the change scores were
      adjusted for baseline levels. A familial correlation model was used to determine
      the heritability of each phenotype using maximum likelihood techniques. RESULTS:
      Significant familial resemblance was observed at baseline and for 7-year changes
      in all phenotypes. At baseline, moderate heritabilities were observed [body mass:
      heritability coefficient (h(2)) = 56%; BMI, h(2) = 39%; SF5, h(2) = 41%; and WC,
      h(2) = 39%], whereas values were attenuated for each change score except for WC
      (Deltabody mass, h(2) = 23%; DeltaBMI, h(2) = 14%; DeltaSF5, h(2) = 12%; and
      DeltaWC, h(2) = 45%). DISCUSSION: Changes in body mass and adiposity
      significantly aggregate within families over 7 years. However, baseline values
      are characterized by higher heritability levels except WC. The significant
      heritabilities observed for change scores suggest that lifestyle, transient
      environmental factors, and possibly age-related gene effects are important
      determinants of changes in body mass and adiposity.

PMID- 12055329
TI  - Relationship between body mass index and the use of healthcare services in
      Australia.
AB  - OBJECTIVE: To examine the relationship between body mass index (BMI) and the use
      of medical and preventive health services. RESEARCH METHODS AND PROCEDURES: This
      study involved secondary analysis of weighted data from the Australian 1995
      National Health Survey. The study was a population survey designed to obtain
      national benchmark information about a range of health-related issues. Data were
      available from 17,033 men and 17,174 women, > or =20 years or age. BMI, based on
      self-reported weight and height, was analyzed in relation to the use of medical
      services and preventive health services. RESULTS: A positive relationship was
      found between BMI and medical service use, such as medication use, visits to
      hospital accident and emergency departments (for women only); doctor visits,
      visits to a hospital outpatient clinics; and visits to other health professionals
      (for women only). A negative relationship was found in women between BMI and
      preventive health services. Underweight women were found to be significantly less
      likely to have Papanicolaou smear tests, breast examinations, and mammograms.
      DISCUSSION: This research shows that people who fall outside the healthy weight
      range are more likely to use a range of medical services. Given that the BMI of
      industrialized populations appears to be increasing, this has important
      ramifications for health service planning and reinforces the need for obesity
      prevention strategies at a population level.

PMID- 12055328
TI  - Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator
      activated receptor gamma.
AB  - OBJECTIVE: To verify whether polyunsaturated fatty acids (PUFAs) can regulate the
      expression of the nuclear receptor peroxisome proliferator-activated receptor
      gamma (PPARgamma) in human adipose tissue. RESEARCH METHODS AND PROCEDURES: The
      effect of various PUFAS on PPARgamma1 and -gamma2 mRNA expression was
      investigated in freshly isolated adipocytes prepared from fat samples obtained
      during surgery. PPARgamma mRNA levels were also determined in subcutaneous
      adipose tissue biopsies of 11 obese women, in the fasting state, to search for in
      vivo associations between PPARgamma expression and plasma PUFA concentrations.
      PPARgamma mRNA levels were determined by reverse-transcription competitive
      polymerase chain reaction. RESULTS: Eicosapentaenoic acid (EPA) significantly
      increased PPARgamma1 mRNA levels in isolated adipocytes, without affecting the
      expression of PPARgamma2. The other tested fatty acids (linolenic acid,
      docosahexaenoic acid and omega-6 PUFAs) had no effect. The effect of EPA was
      dependent on the concentration (maximal effect after 6 hours with 50 microM) and
      was not reproduced by activators of the different members of the PPAR family. In
      addition, a strong positive correlation was found between plasma EPA
      concentrations and PPARgamma mRNA levels in adipose tissue of obese subjects.
      DISCUSSION: Our results demonstrate that adipose tissue PPARgamma1 mRNA
      concentration is positively regulated by EPA, suggesting that the composition of
      dietary lipids may affect PPARgamma gene expression in vivo in humans. These data
      also suggest that an induction of the expression of this nuclear receptor isoform
      might be involved in the mechanism of action of EPA and in some of its beneficial
      effects.

PMID- 12055330
TI  - Effects of fluoxetine administration on neuropeptide y and orexins in obese
      zucker rat hypothalamus.
AB  - OBJECTIVE: The aim of this work was to study the potential involvement of
      neuropeptide Y (NPY) and orexins in the anorexigenic mechanism of fluoxetine in
      obese Zucker rats, assessing the effects of chronic fluoxetine treatment on NPY
      and orexin immunostaining in several hypothalamic regions. RESEARCH METHODS AND
      PROCEDURES: Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg
      intraperitoneally) daily for 2 weeks. The control group was administered 0.9%
      NaCl solution. Carcass composition was assessed using the official methods of the
      Association of Official Analytical Chemists. To test the potential thermogenic
      effect of fluoxetine administration, total body oxygen consumption was measured
      daily for 60 minutes before fluoxetine or saline injection and for 30 minutes
      after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei,
      and the lateral hypothalamic area were immunostained for NPY, orexin A, and
      orexin B. Commercial kits were used for serum determinations. RESULTS: Chronic
      fluoxetine administration in obese Zucker rats generated a reduction in body
      weight gain, food intake, adipocyte size, fat mass, and body protein. A decrease
      in NPY immunostaining in the paraventricular nucleus, without changes in the
      arcuate, was observed. However, no changes were observed in the number of neural
      cells immunostained for orexin A or orexin B in the lateral hypothalamic area.
      DISCUSSION: Due to the hyperphagic effect of NPY in the paraventricular nucleus,
      these results suggest that NPY, but not orexins, could be involved in the
      anorexigenic effect of fluoxetine in obese Zucker rats.

PMID- 12055331
TI  - Obesity increases the risk of spontaneous abortion during infertility treatment.
AB  - OBJECTIVE: This study examines the relationship between body mass and the risk of
      spontaneous abortion in a large cohort of patients who received infertility
      treatment. RESEARCH METHODS AND PROCEDURES: This is a retrospective study using
      data on pregnancies (n = 2349) achieved after treatment in a tertiary medical
      center from 1987 to 1999. One pregnancy per subject was included, and the
      subjects were stratified into five body mass groups based on body mass index
      (BMI): underweight, <18.5 kg/m(2); normal, 18.5 to 24.9 kg/m(2); overweight, 25
      to 29.9 kg/m(2); obese, 30 to 34.9 kg/m(2); and very obese, > or =35 kg/m(2).
      Logistical regression analysis was used. RESULTS: The overall incidence of
      spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of
      spontaneous abortion was significant after adjusting for several independent risk
      factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m(2)),
      underweight women had a similar risk of spontaneous abortion, whereas there was
      progressive increase of risk in overweight, obese, and very obese groups (p <
      0.05, p < 0.01, and p < 0.001, respectively). DISCUSSION: Of all known risk
      factors for spontaneous abortion, the control of obesity has great significance
      because it is noninvasive, potentially modifiable, possibly amenable to low cost,
      and self-manageable by patients. This study established a positive relationship
      between BMI and the risk of spontaneous abortion in women who became pregnant
      after assisted reproductive technology treatment.

PMID- 12055332
TI  - In vivo response to alpha(1)-adrenoreceptor stimulation in human white adipose
      tissue.
AB  - OBJECTIVE: Recent studies in rats suggest an important effect of alpha(1)
      adrenoreceptor stimulation on glucose uptake in white adipocytes. It is not known
      if alpha(1)-adrenoreceptor stimulation elicits similar metabolic effects in
      humans. RESEARCH METHODS AND PROCEDURES: Three microdialysis catheters in
      abdominal subcutaneous adipose tissue were perfused with 0.00, 0.01, 0.10, 1.00,
      and 10.00 microM isoproterenol, phenylephrine, or phenylephrine plus 100 microM
      propranolol. Dialysate concentrations of ethanol, glycerol, glucose, and lactate
      were measured for estimating blood flow (ethanol-dilution technique), lipolysis,
      and glycolysis, respectively. RESULTS: Phenylephrine, with or without
      propranolol, did not elicit a change in ethanol ratio. In contrast, the ethanol
      ratio decreased markedly with isoproterenol. Dialysate glucose concentration
      decreased with phenylephrine with and without propranolol and increased with
      isoproterenol. Phenylephrine caused a dose-dependent increase in dialysate
      glycerol concentration, with a maximal effect similar to that of isoproterenol.
      The effect was attenuated with propranolol. DISCUSSION: Our findings suggest that
      alpha(1)-adrenoreceptor stimulation by phenylephrine increases glucose uptake and
      metabolism in human abdominal adipose tissue. Furthermore, phenylephrine elicits
      a marked increase in lipolytic activity in white adipose tissue through beta
      adrenoreceptor activation.

PMID- 12055333
TI  - Weight loss and bone mineral content.

PMID- 12055334
TI  - Combining behavioral and pharmacological treatments for obesity.
AB  - Weight-loss medications are currently recommended for use only as an adjunct to
      diet, exercise, and behavior modification. Little, however, is known about the
      benefits of combining behavioral and pharmacological therapies or about the
      mechanisms that would make these combined approaches more effective than either
      used alone. This article reviews the effects of adding pharmacotherapy (i.e.,
      principally sibutramine and orlistat) to a modest program of lifestyle
      modification. Studies revealed that the addition of medication typically improved
      short- and long-term weight loss compared with lifestyle modification alone. The
      best results, however, were obtained when medications were combined with an
      intensive, group program of lifestyle modification. The two approaches may have
      additive effects; behavioral treatment seems to help obese individuals control
      the external (i.e., food-related) environment, whereas pharmacotherapy may
      control the internal environment by reducing hunger, cravings, or nutrient
      absorption. The article examines possible methods of sequencing behavioral and
      pharmacological therapies and offers suggestions for future research.

PMID- 12055335
TI  - Body composition of the male and female reference infants.
AB  - During infancy, especially early infancy, a substantial proportion of the
      requirements for energy and specific nutrients are those needed for growth.
      Knowledge of the body composition of a reference infant (body size and chemical
      composition at the 50th centile for age) permits an estimate of the growth needs
      of the infant. In this communication, we review efforts from the 1960s to the
      present at defining the composition of the male and female reference infants. We
      and others have demonstrated that accumulation of fat is remarkably rapid during
      the first 4 or 6 months of life. As a percentage of fat-free mass, water
      decreases throughout infancy whereas protein and minerals increase. However, the
      quantitative nature of these changes remains uncertain. After identifying the
      areas in which further data are needed, we conclude that the single most
      important area for further work is determining the relation of "bone mineral
      content" determined by dual energy X-ray absorptiometry to the osseous mineral
      content of the infant.

PMID- 12055336
TI  - Dietary flavonoids: bioavailability, metabolic effects, and safety.
AB  - Flavonoids comprise the most common group of plant polyphenols and provide much
      of the flavor and color to fruits and vegetables. More than 5000 different
      flavonoids have been described. The six major subclasses of flavonoids include
      the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin),
      flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g.,
      epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and
      isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants
      are attached to sugars (glycosides), although occasionally they are found as
      aglycones. Interest in the possible health benefits of flavonoids has increased
      owing to their potent antioxidant and free-radical scavenging activities observed
      in vitro. There is growing evidence from human feeding studies that the
      absorption and bioavailability of specific flavonoids is much higher than
      originally believed. However, epidemiologic studies exploring the role of
      flavonoids in human health have been inconclusive. Some studies support a
      protective effect of flavonoid consumption in cardiovascular disease and cancer,
      other studies demonstrate no effect, and a few studies suggest potential harm.
      Because there are many biological activities attributed to the flavonoids, some
      of which could be beneficial or detrimental depending on specific circumstances,
      further studies in both the laboratory and with populations are warranted.

PMID- 12055337
TI  - Nutritional impact of intestinal helminthiasis during the human life cycle.
AB  - Poor people in developing countries endure the burden of disease caused by four
      common species of soil-transmitted nematode that inhabit the gastrointestinal
      tract. Disease accompanying these infections is manifested mainly as nutritional
      disturbance, with the differing infections having their deleterious effects at
      different phases during the human life cycle. Reduced food intake, impaired
      digestion, malabsorption, and poor growth rate are frequently observed in
      children suffering from ascariasis and trichuriasis. Poor iron status and iron
      deficiency anemia are the hallmarks of hookworm disease. The course and outcome
      of pregnancy, growth, and development during childhood and the extent of worker
      productivity are diminished during hookworm disease. Less is known about the
      impact of these infections in children under 2 years of age. The severity of
      disease caused by soil-transmitted nematodes has consistently been found to
      depend on the number of worms present per person. Cost-effective measures based
      on highly efficacious anthelminthic drugs are now available to reduce and control
      disease caused by these infections.

PMID- 12055338
TI  - Regulation of nitric oxide synthesis by dietary factors.
AB  - Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS). As an
      endothelium-derived relaxing factor, a mediator of immune responses, a
      neurotransmitter, a cytotoxic free radical, and a signaling molecule, NO plays
      crucial roles in virtually every cellular and organ function in the body. The
      discovery of NO synthesis has unified traditionally diverse research areas in
      nutrition, physiology, immunology, pathology, and neuroscience. Increasing
      evidence over the past decade shows that many dietary factors, including protein,
      amino acids, glucose, fructose, cholesterol, fatty acids, vitamins, minerals,
      phytoestrogens, ethanol, and polyphenols, are either beneficial to health or
      contribute to the pathogenesis of chronic diseases partially through modulation
      of NO production by inducible NOS or constitutive NOS. Although most published
      studies have focused on only a single nutrient and have generated new and
      exciting knowledge, future studies are necessary to investigate the interactions
      of dietary factors on NO synthesis and to define the underlying molecular
      mechanisms.

PMID- 12055339
TI  - Regulation of enzymes of the urea cycle and arginine metabolism.
AB  - The urea cycle is comprised of five enzymes but also requires other enzymes and
      mitochondrial amino acid transporters to function fully. The complete urea cycle
      is expressed in liver and to a small degree also in enterocytes. However, highly
      regulated expression of several enzymes present in the urea cycle occurs also in
      many other tissues, where these enzymes are involved in synthesis of nitric
      oxide, polyamines, proline and glutamate. Glucagon, insulin, and glucocorticoids
      are major regulators of the expression of urea cycle enzymes in liver. In
      contrast, the "urea cycle" enzymes in nonhepatic cells are regulated by a wide
      range of pro- and antiinflammatory cytokines and other agents. Regulation of
      these enzymes is largely transcriptional in virtually all cell types. This review
      emphasizes recent information regarding roles and regulation of urea cycle and
      arginine metabolic enzymes in liver and other cell types.

PMID- 12055340
TI  - Nutritional impact of pre- and probiotics as protective gastrointestinal
      organisms.
AB  - The health benefits of pre- and probiotics have been the subject of increased
      research interests. These food supplements have been demonstrated to alter the
      pre-existing intestinal flora so as to provide an advantage to the host. This
      review focuses on the scientific evidence both for and against their role in
      promoting health and treating disease. Specific attention is turned to their
      effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea,
      Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel
      disease.

PMID- 12055341
TI  - Hydroxylase enzymes of the vitamin D pathway: expression, function, and
      regulation.
AB  - Vitamin D is a secosteroid that is metabolically activated and degraded through
      the actions of three cytochrome P450 hydroxylase enzymes. Bioactivation occurs
      through the sequential actions of cytochromes P450C25 and P450C1, resulting in
      synthesis of the pleiotropic hormone 1,25-dihydroxyvitamin D (1,25VD), which
      regulates over 60 genes whose actions include those associated with calcium
      homeostasis and immune responses as well as cellular growth, differentiation, and
      apoptosis. Inactivation of 1,25VD occurs by C23/C24 oxidation pathways that are
      catalyzed by the multifunctional cytochrome P450C24 enzyme. Both P450C1 and
      P450C24 are highly regulated enzymes whose differential expression is controlled
      in response to numerous cellular modulatory agents such as parathyroid hormone
      (PTH), calcitonin, interferon gamma, calcium, phosphorus, and pituitary hormones
      as well as the secosteroid hormone 1,25VD. Most thoroughly studied at the
      molecular level are the actions of PTH to upregulate P450C1 gene expression and
      1,25VD to induce the expression of P450C24. The regulatory action of PTH is
      mediated through the protein kinase A pathway and involves the phosphorylation of
      transcription factors that function at the proximal promoter of the P450C1 gene.
      The upregulation of P450C24 by 1,25VD has both a rapid nongenomic and a slower
      genomic component that are functionally linked. The rapid response involves
      protein kinase C and mitogen-activated protein kinase (MAPK) pathways that direct
      the phosphorylation of nuclear transcription factors. The slower genomic actions
      are linked to the binding of 1,25VD to the vitamin D receptor (VDR) and the
      interaction of the VDR-1,25VD complex with its heterodimer partner retinoid-X
      receptor and associated coactivators. The regulatory complex is assembled on
      vitamin D response elements in the proximal promoter of the P450C24 gene and
      functions to increase the transcription rate.

PMID- 12055342
TI  - PPAR(gamma) and glucose homeostasis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor involved in the control of metabolism. Research on PPARgamma is oriented
      towards understanding its role in insulin sensitization, which was inspired by
      the discovery that antidiabetic agents, the thiazolidinediones, were agonists for
      PPARgamma. PPARgamma stimulation improves glucose tolerance and insulin
      sensitivity in type 2 diabetic patients and in animal models of insulin
      resistance through mechanisms that are incompletely understood. Upon activation,
      PPARgamma heterodimerizes with retinoid X receptor, recruits specific cofactors,
      and binds to responsive DNA elements, thereby stimulating the transcription of
      target genes. Because PPARgamma is highly enriched in adipose tissue and because
      of its major role in adipocyte differentiation, it is thought that the effects of
      PPARgamma in adipose tissue are crucial to explain its role in insulin
      sensitization, but recent studies have highlighted the contribution of other
      tissues as well. Although relatively potent for their insulin-sensitizing action,
      currently marketed PPARgamma activators have some important undesirable side
      effects. These concerns led to the discovery of new ligands with potent
      antidiabetic properties but devoid of certain of these side effects. Data from
      human genetic studies and from PPARgamma heterozygous knockout mice indicate that
      a reduction in PPARgamma activity could paradoxically improve insulin
      sensitivity. These findings suggest that modulation of PPARgamma activity by
      partial agonists or compounds that affect cofactor recruitment might hold promise
      for the treatment of insulin resistance.

PMID- 12055343
TI  - In vivo kinetics of folate metabolism.
AB  - Investigation of the in vivo kinetics of folate metabolism provides information
      that contributes to a better understanding of the manner in which this vitamin is
      processed in vivo. Kinetic studies can yield insight into the requirements for
      folate, especially with respect to factors that may lead to increased
      requirements. This review considers the strengths and weaknesses of various
      approaches to the study of folate kinetics and resulting data, followed by a
      summary and interpretation of existing data.

PMID- 12055344
TI  - Biotin in metabolism and molecular biology.
AB  - Biotin is a water-soluble vitamin required by all organisms by virtue of its
      essential role in carboxylation reactions. Although the metabolism and role of
      biotin in intermediary metabolism are well established, biotin remains one of the
      most poorly understood water-soluble vitamins in terms of nutritional
      requirements and responsiveness to physiological and pharmacological states.
      Significant advances in the understanding of biotin nutriture have been recently
      accomplished through the description of the kinetics and regulation of biotin
      transport and improved methods for biotin status assessment. Additionally, the
      potential role of biotin in the regulation of gene expression has been
      strengthened through description of altered gene expression during biotin
      deficiency and through newly described enzymatic activities of the enzyme
      biotinidase. Given mounting evidence of suboptimum biotin status, a more complete
      understanding of these aspects of biotin should lead to a greater appreciation of
      the ways in which biotin aids in the maintenance of health.

PMID- 12055345
TI  - Malnutrition and poverty.
AB  - This paper is an attempt to discuss the problem of malnutrition within the
      framework of the global need for development and the challenges posed by the
      trends of neoliberalism and globalization. We argue that there is a two-way link
      between poverty and health in which nutrition plays an important role both as an
      active and as a mediating factor. Key concepts are exposed and expanded: (a)
      Development per se does not ensure better health; (b) unequal distribution of
      income has an independent effect on health indicators after adjusting for total
      income; (c) improving health can make an important contribution to reducing
      poverty; (d ) improving nutrition throughout the whole life course is an
      indispensable strategy for better health; (e) obesity has to be included amongst
      the most critical health problems, has different traits, and presents with
      different challenges in the developing world and in the industrialized countries.

PMID- 12055346
TI  - Genetic effects of methylation diets.
AB  - DNA methylation at cytosines in CpG dinucleotides can lead to changes in gene
      expression and function without altering the primary sequence of the DNA.
      Methylation can be affected by dietary levels of methyl-donor components, such as
      folic acid. This may be an important mechanism for environmentally induced
      changes in gene expression. Recent literature supports a role for DNA-methylation
      changes in a number of adult-onset disorders and during development. These
      changes may be significant for better understanding certain birth defects (e.g.,
      neural tube defects) and the long-term consequences of early environmental
      influences on gene expression (metabolic programming). Optimal "methylation
      diets" should be investigated as part of the prevention and treatment of all
      these conditions, as well as in disorders such as Rett syndrome, whose primary
      defects may lie in DNA methylation-dependent gene regulation.

PMID- 12055347
TI  - How host-microbial interactions shape the nutrient environment of the mammalian
      intestine.
AB  - Humans and other mammals are colonized by a vast, complex, and dynamic consortium
      of microorganisms. One evolutionary driving force for maintaining this
      metabolically active microbial society is to salvage energy from nutrients,
      particularly carbohydrates, that are otherwise nondigestible by the host. Much of
      our understanding of the molecular mechanisms by which members of the intestinal
      microbiota degrade complex polysaccharides comes from studies of Bacteroides
      thetaiotaomicron, a prominent and genetically manipulatable component of the
      normal human and mouse gut. Colonization of germ-free mice with B.
      thetaiotaomicron has shown how this anaerobe modifies many aspects of intestinal
      cellular differentiation/gene expression to benefit both host and microbe. These
      and other studies underscore the importance of understanding precisely how
      nutrient metabolism serves to establish and sustain symbiotic relationships
      between mammals and their bacterial partners.

PMID- 12055348
TI  - Sarcopenia, weight loss, and nutritional frailty in the elderly.
AB  - The progression of the aging process leads to a decreased margin of homeostatic
      reserve and a reduced ability to accommodate metabolic challenges, including
      nutritional stress. Nutritional frailty refers to the disability that occurs in
      old age owing to rapid, unintentional loss of body weight and loss of lean body
      mass (sarcopenia). Sarcopenia, a loss of muscle mass and strength, contributes to
      functional impairment. Weight loss is commonly due to a reduction in food intake;
      its possible etiology includes a host of physiological and nonphysiological
      causes. The release of cytokines during chronic disease may also be an important
      determinant of frailty. In addition to being anorectic, cytokines also contribute
      to lipolysis, muscle protein breakdown, and nitrogen loss. Whereas the multiple
      causes of nutritional frailty are not completely understood, clinical
      interventions for weight loss, sarcopenia, and cytokine alterations have been
      used with modest success.

PMID- 12055349
TI  - Muscle triglyceride and insulin resistance.
AB  - Skeletal muscle contains the majority of the body's glycogen stores and a similar
      amount of readily accessible energy as intramyocellular triglyceride (imTG).
      While a number of factors have been considered to contribute to the pathogenesis
      of insulin resistance (IR) in obesity and type 2 diabetes mellitus (DM), this
      review will focus on the potential role of skeletal muscle triglyceride content.
      In obesity and type 2 DM, there is an increased content of lipid within and
      around muscle fibers. Changes in muscle in fuel partitioning of lipid, between
      oxidation and storage of fat calories, almost certainly contribute to
      accumulation of imTG and to the pathogenesis of both obesity and type 2 DM. In
      metabolic health, skeletal muscle physiology is characterized by the capacity to
      utilize either lipid or carbohydrate fuels, and to effectively transition between
      these fuels. We will review recent findings that indicate that in type 2 DM and
      obesity, skeletal muscle manifests inflexibility in the transition between lipid
      and carbohydrate fuels. This inflexibility in fuel selection by skeletal muscle
      appears to be related to the accumulation of imTG and is an important aspect of
      IR of skeletal muscle in obesity and type 2 DM.

PMID- 12055350
TI  - The role of vitamin A in mammalian reproduction and embryonic development.
AB  - Since the late 1980s, there has been an explosion of information on the molecular
      mechanisms and functions of vitamin A. This review focuses on the essential role
      of vitamin A in female reproduction and embryonic development and the metabolism
      of vitamin A (retinol) that results in these functions. Evidence strongly
      supports that in situ-generated all-trans retinoic acid (atRA) is the functional
      form of vitamin A in female reproduction and embryonic development. This is
      supported by the ability to reverse most reproductive and developmental blocks
      found in vitamin A deficiency with atRA, the block in embryonic development that
      occurs in retinaldehyde dehydrogenase type 2 null mutant mice, and the essential
      roles of the retinoic acid receptors, at least in embryogenesis. Early studies of
      embryos from marginally vitamin A-deficient (VAD) pregnant rats revealed a
      collection of defects called the vitamin A-deficiency syndrome. The manipulation
      of all-trans retinoic acid (atRA) levels in the diet of VAD female rats
      undergoing a reproduction cycle has proved to be an important new tool in
      deciphering the points of atRA function in early embryos and has provided a means
      to generate large numbers of embryos at later stages of development with the
      vitamin A-deficiency syndrome. The essentiality of the retinoid receptors in
      mediating the activity of atRA is exemplified by the many compound null mutant
      embryos that now recapitulate both the original vitamin A-deficiency syndrome and
      exhibit a host of new defects, many of which can also be observed in the VAD-atRA
      supported rat embryo model and in retinaldehyde dehydrogenase type 2 (RALDH2)
      mutant mice. A major task for the future is to elucidate the atRA-dependent
      pathways that are normally operational in vitamin A-sufficient animals and that
      are perturbed in deficiency, thus leading to the characteristic VAD phenotypes
      described above.

PMID- 12055351
TI  - Fatty acid transport across membranes: relevance to nutrition and metabolic
      pathology.
AB  - Long-chain fatty acids are an important constituent of the diet and they
      contribute to a multitude of cellular pathways and functions. Uptake of long
      chain fatty acids across plasma membranes is the first step in fatty acid
      utilization, and recent evidence supports an important regulatory role for this
      process. Although uptake of fatty acids involves two components, passive
      diffusion through the lipid bilayer and protein-facilitated transfer, the latter
      component appears to play the major role in mediating uptake by key tissues.
      Identification of several proteins as fatty acid transporters, and emerging
      evidence from genetically altered animal models for some of these proteins, has
      contributed significant insight towards understanding the limiting role of
      transport in the regulation of fatty acid utilization. We are also beginning to
      better appreciate how disturbances in fatty acid utilization influence general
      metabolism and contribute to metabolic pathology.

PMID- 12055352
TI  - Physiologic determinants of the anorexia of aging: insights from animal studies.
AB  - The anorexia of aging is a syndrome characterized by unexplained losses in food
      intake and body weight that occur near the end of life. Proposed etiologies cover
      a wide range of biological and psychological conditions. The observation of this
      phenomenon in older laboratory animals suggests that physiological changes play a
      significant causal role. Research on the neurochemical control of energy balance
      has received much attention in recent years, and age-related alterations in the
      neuropeptidergic effectors of food intake have been implicated in the anorexia of
      aging. This review provides an update on putative mechanisms underlying this
      dysregulation of feeding during advanced age.

PMID- 12055353
TI  - Ceruloplasmin metabolism and function.
AB  - Ceruloplasmin is a serum ferroxidase that contains greater than 95% of the copper
      found in plasma. This protein is a member of the multicopper oxidase family, an
      evolutionarily conserved group of proteins that utilize copper to couple
      substrate oxidation with the four-electron reduction of oxygen to water. Despite
      the need for copper in ceruloplasmin function, this protein plays no essential
      role in the transport or metabolism of this metal. Aceruloplasminemia is a
      neurodegenerative disease resulting from inherited loss-of-function mutations in
      the ceruloplasmin gene. Characterization of this disorder revealed a critical
      physiological role for ceruloplasmin in determining the rate of iron efflux from
      cells with mobilizable iron stores and has provided new insights into human iron
      metabolism and nutrition.

PMID- 12055354
TI  - Metabolic lessons from genetically lean mice.
AB  - Different types of lean mice have been produced by genetic manipulation. Leanness
      can result from deficiency of stored energy or a lack of adipocytes to store the
      lipid. Mice lacking functional adipocytes are usually insulin resistant and have
      fatty livers, and elevated circulating triglyceride levels. Insulin resistance
      may result from the lack of adipocyte hormones (such as leptin) and increased
      metabolite (such as triglyceride) levels in nonadipose tissue. Mice with depleted
      adipocyte triglyceride levels typically are insulin sensitive and have normal or
      low liver and circulating triglycerides. Mechanisms to produce depleted
      adipocytes include increased energy expenditure by peripheral tissues, peripheral
      mechanisms to decrease food intake, and altered central regulation of these
      processes.

PMID- 12055355
TI  - Carotenoid bioavailability and bioconversion.
AB  - The possible role of carotenoids and their metabolites in disease prevention is
      far from fully understood, because the bioavailabilities of carotenoids are
      complicated by multiple factors that affect their absorption, breakdown,
      transport, and storage. Rapid progress in developing sophisticated methodologies,
      including use of stable-isotope dilution methods, now allows for an accurate
      determination of the true vitamin A activity of provitamin A carotenoids. The
      recent identification of specific enzymes, which catalyze the breakdown of beta
      carotene as well as nonprovitamin A carotenoids, is providing a better
      understanding of the functions of carotenoids at the molecular level. The
      pathways and possible mechanisms of carotenoid breakdown and factors affecting
      the bioavailability of carotenoids, such as carotenoid type, food matrix,
      interaction with other carotenoids and other food components, nutritional status,
      aging, and infection, are discussed in this review.

PMID- 12055356
TI  - Dietary conjugated linoleic acid in health: physiological effects and mechanisms
      of action.
AB  - Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids found in
      beef, lamb, and dairy products that exist as positional and stereo-isomers of
      octadecadienoate (18:2). Over the past two decades numerous health benefits have
      been attributed to CLA in experimental animal models including actions to reduce
      carcinogenesis, atherosclerosis, onset of diabetes, and body fat mass. The
      accumulation of CLA isomers and several elongated/desaturated and beta-oxidation
      metabolites have been found in tissues of animals fed diets with CLA. Molecular
      mechanisms of action appear to include modulation of eicosanoid formation as well
      as regulation of the expression of genes coding for enzymes known to modulate
      macronutrient metabolism. This review focuses on health benefits, metabolism, and
      potential mechanisms of action of CLA and postulates the implications regarding
      dietary CLA for human health.

PMID- 12055358
TI  - How doctors should react to domestic violence.

PMID- 12055359
TI  - Risk factors for preterm delivery in women with placenta praevia and antepartum
      haemorrhage: retrospective study.
AB  - OBJECTIVE: To identify risk factors for preterm delivery in women with placenta
      praevia and antepartum haemorrhage. DESIGN: Retrospective study. SETTING:
      Regional obstetric unit, Hong Kong. SUBJECTS AND METHODS: Women delivered at
      Princess Margaret Hospital between 1 January 1990 and 31 December 1997. Possible
      risk factors for preterm delivery among women with placenta praevia and
      antepartum haemorrhage including onset, pattern, and severity of vaginal
      bleeding; presence of uterine contractions on admission; and type of placenta
      were assessed. RESULTS: Three risk factors for preterm delivery were identified
      from univariate analysis. These included second trimester vaginal bleeding (odds
      ratio=4.19; 95% confidence interval, 1.29-13.66), the presence of uterine
      contractions on admission (odds ratio=4.00; 95% confidence interval, 1.57-10.19),
      and a haemoglobin decrease of more than 20 g/L (odds ratio=3.00; 95% confidence
      interval, 1.00-9.04). Using the logistic regression model, second trimester
      vaginal bleeding and the presence of uterine contractions were found to be
      independent risk factors for delivery before 36 weeks. CONCLUSION: Preterm
      delivery is increased in women with placenta praevia and antepartum haemorrhage
      who have second trimester vaginal bleeding or the presence of uterine
      contractions. This high-risk group may benefit from close in-patient monitoring
      and more aggressive management.

PMID- 12055357
TI  - Phytosterols in human nutrition.
AB  - Phytosterols are cholesterol-like molecules found in all plant foods, with the
      highest concentrations occurring in vegetable oils. They are absorbed only in
      trace amounts but inhibit the absorption of intestinal cholesterol including
      recirculating endogenous biliary cholesterol, a key step in cholesterol
      elimination. Natural dietary intake varies from about 167-437 mg/day. Attempts to
      measure biological effects in feeding studies have been impeded by limited
      solubility in both water and fat. Esterification of phytosterols with long-chain
      fatty acids increases fat solubility by 10-fold and allows delivery of several
      grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester
      reduces low density lipoprotein cholesterol by 10%, and little difference is
      observed between Delta(5)-sterols and 5alpha-reduced sterols (stanols).
      Phytosterols can also be dispersed in water after emulsification with lecithin
      and reduce cholesterol absorption when added to nonfat foods. In contrast to
      these supplementation studies, much less is known about the effect of low
      phytosterol levels in the natural diet. However, reduction of cholesterol
      absorption can be measured at a dose of only 150 mg during otherwise sterol-free
      test meals, suggesting that natural food phytosterols may be clinically
      important. Current literature suggests that phytosterols are safe when added to
      the diet, and measured absorption and plasma levels are very small. Increasing
      the aggregate amount of phytosterols consumed in a variety of foods may be an
      important way of reducing population cholesterol levels and preventing coronary
      heart disease.

PMID- 12055360
TI  - Normal 24-hour ambulatory proximal and distal gastroesophageal reflux parameters
      in Chinese.
AB  - OBJECTIVE: To quantify normal proximal and distal oesophageal acid parameters in
      healthy Chinese. DESIGN: Observational study. SETTING: University teaching
      hospital, Hong Kong. SUBJECTS AND METHODS: Twenty healthy adults who were not on
      medication and were free from gastrointestinal symptoms were recruited by
      advertisement. Ambulatory oesophageal acid (pH<4) exposure parameters were
      recorded at distal and proximal sites, 5 and 20 cm, respectively above the lower
      oesophageal sphincter. RESULTS: The 95th percentile for reflux parameters
      assessed in the distal/proximal oesophagus were: percent total time pH<4,
      4.6/0.7%; percent upright time pH<4, 7.0/1.1%; percent supine time pH<4,
      4.5/0.5%; number of reflux episodes, 73/12; number of reflux episodes with pH<4
      for >5 minutes, 4/0; and the longest single acid exposure episode, 11.2/3.0
      minutes. CONCLUSION: Physiological gastroesophageal reflux occurs in healthy
      Chinese. These initial data provide a preliminary reference range that could be
      utilised by laboratories studying Chinese subjects.

PMID- 12055361
TI  - Evaluation of a new handheld biosensor for point-of-care testing of whole blood
      beta-hydroxybutyrate concentration.
AB  - OBJECTIVES: To evaluate performance characteristics of the newly available
      handheld combined glucose and ketone meter for beta-hydroxybutyrate measurement.
      DESIGN: Laboratory method evaluation. MAIN OUTCOME MEASURES: Accuracy of beta
      hydroxybutyrate measurement and effect of acetoacetate interference at clinically
      important beta-hydroxybutyrate levels. RESULTS: Deming regression analysis of
      beta-hydroxybutyrate measurements assessed by the ketone sensor and a laboratory
      enzymatic method revealed a coefficient of determination of 0.989 (P<0.001).
      Passing-Bablok regression analysis showed a linear relationship between the two
      methods, ie Y= -0.32+1.13X. The 95% confidence interval of the slope and y
      intercept were: slope=1.13 (95% confidence interval, 1.04 to 1.22); intercept= 
      0.32 (95% confidence interval, -0.59 to -0.06). The Bland-Altman plot showed a
      small proportional bias between the two methods. The mean bias +/-2 standard
      deviations was between -0.53 and 0.67 mmol/L. Beta-hydroxybutyrate measurements
      made by the sensor were linear up to 6 mmol/L. Replicate analysis of two samples
      spiked with 3.6 mmol/L and 0.8 mmol/L of beta-hydroxybutyrate resulted in
      coefficients of variation of 3.3% and 13%, respectively. The presence of
      acetoacetate caused a negative interference in beta-hydroxybutyrate measurement.
      Beta-hydroxybutyrate recovery was 97.0% and 90.7% when the ketone body ratios
      were 6:1 and 3:1, respectively. CONCLUSION: The analytical performance of the
      sensor, when operated according to manufacturer's instructions, could meet the
      needs of point-of-care beta-hydroxybutyrate measurement. Additional clinical
      studies are needed to assess the benefits of introducing such an assay in a
      clinical setting.

PMID- 12055362
TI  - Computed tomography evaluation in acute stroke: retrospective study.
AB  - OBJECTIVE: To determine the accuracy with which 'frontline' hospital doctors
      interpret computed tomography brain scans. DESIGN: Retrospective study. SETTING:
      University teaching hospital, Hong Kong. PARTICIPANTS: Medical and emergency room
      doctors. MAIN OUTCOME MEASURE: Accuracy in correctly identifying features of
      acute stroke on 18 computed tomography brain scans. RESULTS: Computed tomography
      brain scan images showing easily detectable haemorrhage and infarct were
      identified in 91% and 90% of scans, respectively; but difficult-to-interpret
      scans with subtle features of haemorrhage or infarct were only correctly
      identified in 46% and 45% of readings, respectively. More experienced doctors did
      not perform better than junior doctors (P=0.69; 95% confidence interval, -1.84 to
      2.73) and the mean total score for doctors from the emergency department did not
      differ significantly from that of doctors from the medical department (P=0.57;
      95% confidence interval, -2.98 to 1.67). CONCLUSION: Early signs of infarct and
      small bleeds on computed tomography brain scans are not well recognised by
      doctors, regardless of clinical exposure or seniority. Ineligible patients may be
      treated with thrombolytic therapy as a result of such computed tomography scan
      misinterpretation.

PMID- 12055363
TI  - Recall of preoperative anaesthesia information in Hong Kong Chinese patients.
AB  - OBJECTIVE: To evaluate the ability of patients to recall information provided
      during a preoperative visit. DESIGN: Qualitative study. SETTING: Regional
      hospital, Hong Kong. PATIENTS: Sixty patients scheduled for elective surgery
      under general anaesthesia or central neuro-axial block. MAIN OUTCOME MEASURES:
      Satisfactory recall of preoperative information, defined as the ability to
      remember at least 75% of adverse effects described. RESULTS: Fifty-nine (98.3%)
      patients were satisfied with the preoperative information. Forty-two (70%)
      patients rated anaesthetic complications as important. At the interview on the
      day of the operation, 57 (95%) patients had satisfactory recall of the
      information provided. Eighty-five percent of patients remembered that the
      information was provided by an anaesthesiologist. After the operation, of those
      who experienced adverse effects, 48 (96%) patients remembered being told to
      anticipate the adverse anaesthetic event. Univariate analysis found that age,
      sex, education level, occupation, and the modality of anaesthesia did not affect
      patient recall of preoperative information on the day of surgery or 1 day
      postsurgery. CONCLUSION. There was satisfactory recall of preoperative
      information by the majority of patients in the study. Most patients expressed
      satisfaction with the information provided.

PMID- 12055364
TI  - Blockade of the renin-angiotensin system.
AB  - The renin-angiotensin-aldosterone system plays a key role in the regulation of
      fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit
      angiotensin-converting enzyme and have been shown to be effective in many
      cardiovascular diseases. They should be considered for the treatment of
      hypertension in patients with heart failure, previous myocardial infarction,
      diabetes, or proteinuria. There are a number of side-effects associated with
      angiotensin-converting enzyme inhibitors, especially persistent dry cough.
      Angiotensin II receptor antagonists (sartans) provide a more specific blockade of
      the renin-angiotensin-aldosterone system and are associated with fewer side
      effects, including cough. Their long-term efficacy and tolerability in the
      treatment of patients with hypertension has, however, yet to be established.
      Periodic monitoring of renal function and electrolytes is required in patients
      treated with an angiotensin-converting enzyme inhibitor or a sartan.

PMID- 12055365
TI  - Living donor liver transplantation without the use of blood products.
AB  - We report on two patients who presented with unresectable hepatocellular
      carcinoma complicating hepatitis B liver cirrhosis. After evaluation, both
      patients were accepted for liver transplantation. Being aware of the scarce
      availability of cadaveric liver grafts and the long waiting time, family members
      volunteered to be donors for the two patients. Living donor liver transplantation
      using right lobe liver grafts, including the middle hepatic vein, was
      subsequently performed without the use of blood products in both the donors and
      recipients. All involved recovered uneventfully from their respective operations.

PMID- 12055366
TI  - Acute pain services in Hong Kong: facilities, volume, and quality.
AB  - Acute pain services in public hospitals in Hong Kong were studied. Audit data on
      the volume and quality of acute pain services were collected prospectively from
      1997 to 1999, and data on related facilities were collected in 2000. About 20% of
      patients undergoing a major operation received an acute pain service; of these,
      78.6% were satisfied with the treatment provided. In 2000, 86% (18/21) of
      hospitals providing anaesthetic services were running an acute pain service.
      Staffing was better in hospitals providing a high volume of acute pain services,
      ranging from a full-time specialist anaesthesiologist assisted by a half-time
      trainee to a half-time specialist assisted by a full- or half-time trainee.
      However, only four hospitals were staffed with pain nurses. In total, 57% of
      patients received intravenous patient-controlled analgesia and 32% epidural
      analgesia. The mean duration of acute pain service treatment was 3.1 days.
      Currently anaesthesiologist-based acute pain services take care of a limited
      number of patients. To expand the coverage, there should be a move towards an
      anaesthesiologist-led, pain nurse-based, acute pain service. The present shortage
      of pain nurses should be addressed.

PMID- 12055367
TI  - Primary hyperoxaluria: a rare but important cause of nephrolithiasis.
AB  - We report on a middle-aged man with end-stage renal failure apparently secondary
      to recurrent renal stones. He developed systemic oxalosis soon after commencing
      dialysis. The diagnosis of primary hyperoxaluria type 1 was supported by the
      finding of high dialysate glycolate excretion. The patient subsequently received
      an isolated cadaveric renal transplant, but the outcome was a rapid recurrence of
      oxalosis and early graft failure. Although isolated liver or renal
      transplantation in addition to various adjuvant measures may be considered in the
      early stage, combined liver-kidney transplantation remains the only definitive
      therapy for a patient with end-stage renal failure and systemic oxalosis due to
      hyperoxaluria type 1. This case illustrates the possible late presentation of
      primary hyperoxaluria type 1 and the poor outcome with isolated renal
      transplantation after the development of systemic oxalosis. One should thus have
      a high index of suspicion in patients with recurrent renal stones of this rare,
      but nevertheless important, entity.

PMID- 12055368
TI  - Ammonia detoxification by continuous venovenous haemofiltration in an infant with
      urea cycle defect.
AB  - We report the case of a newborn baby with carbamoyl phosphate synthetase
      deficiency. He presented at 2 weeks of life, deteriorating to a state of
      hyperammonaemic coma and respiratory failure. Rapid detoxification was
      successfully achieved by continuous venovenous haemofiltration while a definitive
      diagnosis and treatment were determined. The ammonia clearance achieved by
      continuous venovenous haemofiltration was greater than 20 mL/min/m(2), which is
      superior to that achieved by peritoneal dialysis and arteriovenous
      haemofiltration in this age-group.

PMID- 12055369
TI  - Malassezia furfur fungaemia in a ventilator-dependent patient without known risk
      factors.
AB  - Malassezia furfur is the lipophilic yeast which causes tinea versicolor and is an
      uncommon cause of fungaemia. It usually occurs in the context of
      hyperalimentation with lipid emulsion, immunosuppression, or the presence of a
      central venous catheter. We report a case of a ventilator-dependent patient who
      developed Malassezia furfur fungaemia in the absence of these known risk factors.
      A likely risk factor in this patient was receipt of multiple courses of broad
      spectrum antibiotics. This case highlights the importance of recognising
      Malassezia furfur as a cause of fungaemia, as well as the need for special
      culture techniques to aid identification.

PMID- 12055370
TI  - Paediatric stroke: case series.
AB  - Five cases of paediatric stroke are reported. Two patients presented with
      idiopathic stroke, another following vertebral artery dissection, one secondary
      to Moyamoya disease, and one patient with the syndrome of mitochondrial
      encephalopathy, lactic acidosis, and stroke-like episodes. The presentation,
      investigation, and management of paediatric stroke are discussed.

PMID- 12055371
TI  - Legal versus medical causation. Case analysis: Bolitho versus City and Hackney
      Health Authority.

PMID- 12055372
TI  - Lichen amyloidosis.

PMID- 12055375
TI  - Traditions, trends, tomorrow.

PMID- 12055373
TI  - Complementary medicine, acupuncture, and pneumothorax.

PMID- 12055376
TI  - Young adults' perceptions of living with chronic inflammatory bowel disease.
AB  - King's (1981, 1995b) Theory of Goal Attainment provided the theoretical framework
      for this qualitative, descriptive study exploring the perceptions of five young
      adults living with chronic inflammatory bowel disease (IBD). Through in-depth
      interviews, the participants had the opportunity to share their perceptions of
      what mattered most as they lived the experiences of this illness. The uniqueness
      and individuality of perceptions, the challenges of chronic bowel disease,
      recommendations for the future, and participants' expectations of healthcare
      professionals were explored. Persons with chronic IBD are faced with many life
      disrupting challenges that profoundly affect their personal, interpersonal, and
      social systems. This research study supported the premise that understanding the
      patient's perspective and reaching perceptual accuracy through human-to-human
      interaction is critical to healthcare outcomes and achievement of the young
      adult's health goals.

PMID- 12055377
TI  - An overview of diarrhea in the patient receiving enteral nutrition.
AB  - Many healthcare providers associate enteral tube feedings with diarrhea. Research
      suggests an incidence of diarrhea in patients receiving enteral tube feedings of
      2% to 63%. This wide variation in incidence is due, in part, to the lack of a
      universal definition of diarrhea and other suspected factors that influence stool
      output such as malabsorption, infection, bacterial contamination of the feeding,
      medical diagnosis of the patient, medication therapy, or formula-related causes.
      An understanding of digestion, the role of fiber and fat in the diet, and the
      control for other influences will aid nurses in identifying interventions that
      promote a normal stool consistency in patients receiving enteral tube feedings.
      The need for further research regarding the causes and management of diarrhea is
      also supported.

PMID- 12055378
TI  - Carcinoid tumors and syndrome.
AB  - Carcinoid tumors are very rare and originate mainly in the gastrointestinal
      tract. The tumor histology is ambiguous and malignancy is determined by
      metastases. Carcinoid tumors affect both sexes equally and have been found in all
      age groups. Many carcinoid tumors are found incidentally or from symptoms related
      to the hormones that the tumor produces. Carcinoid syndrome occurs when vast
      quantities of hormones are produced from GI carcinoid metastases or a non-GI
      primary tumor. The classic "carcinoid triad" associated with the syndrome
      includes flushing, diarrhea, and cardiac involvement. The hormone largely
      responsible for most of these symptoms is serotonin. Treatment consists of a wide
      resection for local primaries and usually palliative, medical support for
      patients with metastases. The tumors are very slow-growing and patients have
      lived for up to 30 years after metastasis is diagnosed. Somatostatin analogue
      (lanreotide and octreotide) administration controls many of the carcinoid
      symptoms. Somatostatin is a naturally occurring gastrointestinal peptide
      (hormone) which can augment or counteract a wide variety of other peptides. This
      article provides an overview of carcinoid tumor and carcinoid syndrome including
      diagnosis and treatment. Aspects important to patient care will also be
      addressed.

PMID- 12055379
TI  - Establishing the shelf life of flexible colonoscopes.
AB  - This study was designed to establish a shelf life for processed (peracetic acid)
      flexible colonoscopes and to demonstrate the adequacy of manual cleaning
      procedures. The study challenges current practice in Australia where endoscopes
      are routinely reprocessed prior to use if the endoscope has been sitting at least
      overnight. The design was a simulated study in the clinical environment and
      involved artificial contamination of a colonoscope, cleaning validation, and a
      time series analysis after processing with peracetic acid in a Steris System 1
      processor and drying with 100% isopropyl alcohol. The main outcome measure was
      the presence of bacteria in the internal channels of the colonoscope after
      cleaning and at 24 and 168 hours after processing with peracetic acid. The
      findings suggest that colonoscopes may be left for up to 1 week before needing to
      be reprocessed before use, provided all channels are thoroughly reprocessed and
      dried, resulting in cost savings and reduced wear and tear on the instruments.
      The findings also demonstrate the impact of providing feedback to staff on a
      regular basis about the efficacy of their cleaning techniques.

PMID- 12055380
TI  - Quality of life and symptoms after surgery for gastroesophageal cancer: a pilot
      study.
AB  - Oncologic outcomes of gastroesophageal surgery may be similar, but little is
      known about the impact on patients' postoperative symptom experience and quality
      of life (QOL). The purpose of this pilot study was to describe overall QOL and
      symptom experience of individuals who underwent either total gastrectomy with
      Roux-en-Y esophagojejunostomy or esophagogastrectomy for adenocarcinoma of the
      gastroesophageal junction. The Gastroenterology Quality of Life Index (GQLI) and
      the Life After Gastric Surgery (LAGS), developed by the investigators for
      measuring symptom frequency, were used to measure variables of interest. The
      sample (n = 27) had a relatively high QOL, but experienced difficulties with
      eating patterns, physical functioning, socialization, and happiness. There were
      significant differences between the two procedures related to QOL and symptom
      frequency in that individuals who had the total gastrectomy fared somewhat
      better. Further, patients who had esophagogastrectomy had greater symptom
      frequency and significantly poorer QOL. Although initially compelling, these data
      warrant further investigation into the QOL and symptom impact in a more diverse
      population of patients with cancer of the stomach or esophagus. These results,
      however, suggest several areas where nursing interventions could help these
      patients.

PMID- 12055381
TI  - Complementary healthcare practices. Stress management for gastrointestinal
      disorders: the use of kundalini yoga meditation techniques.

PMID- 12055383
TI  - Legislation. Political action committees: why such a mystery?

PMID- 12055382
TI  - Leading the way. A view from the other side.

PMID- 12055384
TI  - Editorial overview: lung cancer.

PMID- 12055385
TI  - Management of advanced non-small cell lung cancer: current trends.
AB  - Carcinoma of the lung continues to be the leading cause of cancer-related deaths
      for Americans. Major efforts have been made in the treatment of advanced non
      small cell lung cancer; chemotherapy and investigations in the last decade have
      yielded a number of new agents and combinations. Despite progress with newer
      agents for the treatment of non-small cell lung cancer, only 14% of patients with
      the disease are alive 5 years after the initial diagnosis. Toward improving the
      outcome of patients with advanced non-small cell lung cancer, a few trends can be
      identified. These include further work on combination chemotherapy, the
      introduction of novel biologic agents into treatment, and predicting which
      patients will respond to chemotherapy. These trends are discussed in this review.

PMID- 12055386
TI  - PET and SPECT in the management of lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths in men and women. Most recently
      in 2001, the Health Care Financing Administration has expanded Medicare coverage
      for positron emission tomography (PET) to include the diagnosis, staging, and
      restaging of lung cancer. This review discusses the current metabolic imaging
      techniques, including the role of PET, single-photon emission computed tomography
      (SPECT), and the new hybrid PET in the diagnosis, staging, and treatment of lung
      cancer. The technological advantages, disadvantages, and benefits are compared.
      PET has the highest detection efficiency than gamma camera based devices. PET
      when merged with computed tomography (CT) forms the powerful hybrid PET-CT
      system, capable both of metabolic and anatomic imaging. Clinical imaging pathways
      based on these newer modalities for the management of lung cancer are proposed.
      Technological advances in metabolic imaging linked with therapy driven protocols
      and outcomes may further provide cutting edge modalities that positively impact
      on dismal lung cancer mortality statistics.

PMID- 12055387
TI  - The molecular biology of lung cancer.
AB  - Lung cancer is the result of molecular changes that occur in the cell, resulting
      in the deregulation of pathways which control normal cellular growth,
      differentiation, and apoptosis. Several of these pathways contain well
      characterized proto-oncogenes and tumor suppressor genes which are found to be
      mutated or have abnormal expression patterns in lung cancer. The molecular
      changes that characterize lung cancer are complex, but it is known that cigarette
      smoking causes most squamous cell and small-cell carcinomas. However, the
      association between cigarette smoke and adenocarcinoma is less clear.
      Environmental factors, such as air pollutants, radon, and asbestos, likely
      contribute to the development of lung cancer. In this review, we discuss the
      major molecular abnormalities in lung cancer with a review of recent studies that
      begin to decipher the role that different tumor suppressor genes and oncogenes
      play in the pathogenesis of lung cancer. Also, we highlight the research that has
      identified new genes which may play a role in lung cancer pathogenesis or
      progression.

PMID- 12055388
TI  - New concepts in lung cancer screening.
AB  - Although spiral CT has an undeniably impressive ability to detect occult lung
      cancers in asymptomatic smokers, it is not clear whether screening this patient
      group will lead to a reduction in disease-specific mortality. The specter of
      overdiagnosis in lung cancer screening, which manifested during the chest
      radiograph trials of the 1970s and 1980s, still hangs over screening regimes
      today. The detection of premalignant lesions by molecular medicine techniques and
      fluorescence bronchoscopy may allow the development of novel treatments for
      preinvasive disease, but it is likely that radiologic means of detection will
      form the front line of any near future screening program. The proposed screening
      techniques may be new, but their use must be tested against tried and trusted
      standards of medical practice.

PMID- 12055389
TI  - Neuroendocrine tumors of the lung: recent developments in histopathology.
AB  - Lung tumors with neuroendocrine differentiation are made up of several neoplasms
      with particular epidemiologic, clinical, morphologic, and molecular
      characteristics. Typical and atypical carcinoid tumors represent low-grade and
      intermediate-grade carcinomas, respectively, whereas small-cell carcinoma and
      large-cell neuroendocrine carcinoma are considered high-grade carcinomas. Recent
      studies support the use of this four-tumor, three-tier classification scheme, but
      in practice, definitive diagnoses on small tissue samples remain a challenge for
      even the most experienced lung pathologists.

PMID- 12055390
TI  - Role of video-assisted thoracoscopic surgery and classic thoracotomy in lung
      cancer management.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. For patients
      diagnosed with early-stage lung cancer, complete surgical resection remains the
      best hope for cure. Limited resections are avoided when possible because of
      higher recurrence rates and potentially worse long-term survival. Traditionally,
      a posterolateral thoracotomy has been used to perform anatomic lung resections
      and mediastinal lymph node dissection for complete staging. More recently, the
      use of video-assisted thoracoscopic surgery has been introduced for the treatment
      of stage I lung cancers. Although thought minimally invasive and thus perceived
      as resulting in less postoperative pain and faster recovery, its acceptance has
      varied worldwide. Questions about training, cost containment, and oncologic
      principles prevail. In essence, the absolute indications and limitations of video
      assisted thoracoscopic surgery for patients with lung cancer have yet to be
      defined.

PMID- 12055391
TI  - Lung cancer staging.
AB  - Accurate staging of lung cancer is essential for proper treatment and management
      of the disease, and allows predictions for patient survival. Several different
      invasive and noninvasive modalities exist for staging, and the determination of
      the best approach of one or a combination of those methods depends on the
      clinical situation and the clinician's assessment of the most appropriate means
      of staging evaluation. This review discusses the elements and framework of lung
      cancer staging, with particular emphasis on those newer modalities, especially
      positron emission tomography and endoscopic ultrasound needle biopsy, which will
      be expected to be used increasingly more common in clinical practice.

PMID- 12055393
TI  - Malignant pleural effusions: treatment with tunneled long-term drainage
      catheters.
AB  - Malignant pleural effusion is a significant cause of morbidity and a poor
      prognostic indicator. Traditional treatments have variable success and
      significant drawbacks, including a length of stay in the hospital. Alternatively,
      a tunneled pleural catheter permits long-term drainage as an outpatient, cost
      effectively controlling the effusion and related symptoms in over 80 to 90% of
      patients. Other advantages are the ability to treat trapped lungs and large
      locules. Spontaneous pleurodesis may occur in over 40% of patients, and the
      catheter can be used to administer sclerosant or antineoplastic agents.
      Complications tend to be minor and easily managed. A tunneled pleural catheter
      should be considered for all patients with MPE having a reasonable expectancy of
      being an outpatient.

PMID- 12055392
TI  - Vascular endothelial growth factor: the key mediator in pleural effusion
      formation.
AB  - Pleural effusion is common in clinical practice. Increased vascular permeability
      and leakage play a principal role in the development of exudative pleural
      effusions. In vitro and in vivo evidence have solidly established vascular
      endothelial growth factor (VEGF), a potent inducer of vascular permeability, as a
      crucial mediator in pleural fluid formation. VEGF is present in high quantities
      in human effusions. In the pleural space, mesothelial cells, infiltrating
      inflammatory cells, and (in malignant pleuritis) cancer cells contribute to the
      VEGF accumulation in the pleural fluids. Pleural fluid VEGF is biologically
      active and may promote tumor growth and chemotaxis. Strategies to antagonize the
      VEGF activity at various target points of its signaling pathway have shown
      success in vitro and in animal models of malignant pleural or peritoneal
      effusions. Novel agents targeting VEGF activities are undergoing clinical trials.
      Regulation of VEGF activity and vascular permeability represent a rapidly
      expanding field of research, which is likely to provide further insight in the
      pathophysiology of pleural fluid formation.

PMID- 12055394
TI  - Pleural effusions after coronary artery bypass graft surgery.
AB  - After coronary artery bypass graft surgery, most patients will have a small,
      unilateral, left-sided pleural effusion, and approximately 10% of patients will
      have a larger effusion. These large effusions can be separated into (1) early
      effusions occurring within the first 30 days of surgery that are bloody exudates
      with a high percentage of eosinophils, and (2) late effusions occurring more than
      30 days after surgery that are clear yellow lymphocytic exudates. The primary
      symptom of pleural effusion after coronary artery bypass graft surgery is
      dyspnea; chest pain and fever are uncommon. Most patients with large pleural
      effusions after coronary artery bypass graft surgery are treated successfully
      with one to three therapeutic thoracenteses.

PMID- 12055395
TI  - Diagnosis and management of lupus pleuritis.
AB  - Systemic lupus erythematosus is a chronic inflammatory autoimmune disorder that
      can affect any organ system. Predominant manifestations include arthralgia, rash,
      photosensitivity, pleuritis, renal and central nervous system involvement.
      Fortunately, pleuritis in systemic lupus erythematosus is not usually as life
      threatening as may be the renal or central nervous system complications.
      Nevertheless, pleuritis does occur in systemic lupus erythematosus and may be a
      significant cause of morbidity. In addition to primary pleuritis attributed to
      systemic lupus erythematosus, secondary pleural complications, especially
      infections, may occur as a consequence of systemic lupus erythematosus. Pleuritis
      in patients with systemic lupus erythematosus may therefore frequently challenge
      the diagnostic and therapeutic acumen of physicians.

PMID- 12055396
TI  - Body cavity lymphoma.
AB  - Body cavity lymphomas (BCLs) are a heterogeneous group of rare, primary non
      Hodgkin's lymphomas that proliferate within the serous body cavities and result
      in recurrent effusions. This review is mainly focussed on the distinct entity
      primary effusion lymphoma (PEL) wherein the tumor clone is infected by human
      herpesvirus-8, the etiologic agent of Kaposi's sarcoma. In addition, we briefly
      discuss here recent data regarding other BCL types. The latter include a subset
      with no evidence of herpesvirus 8 which is associated with Epstein-Barr virus
      (pyothorax-associated lymphoma, PAL), the BCL forms associated to hepatitis C
      virus-related cirrhosis or alcohol-related cirrhosis and, finally, non-neoplastic
      forms mimicking lymphomatous effusions.

PMID- 12055397
TI  - Thoracoscopy in management of postpneumonic pleural infections.
AB  - With expanding overall experience of video-assisted thoracic surgery in the last
      decade, its use in postpneumonic pleural infection is increasing, as shown by a
      larger number of publications advocating its efficacy. The main areas of study in
      the use of video-assisted thoracic surgery in this condition are (1) as an
      alternative to traditional open thoracotomy and (2) as an additional treatment
      option in the management of earlier-stage disease. The benefits of the minimally
      invasive approach are particularly attractive in the treatment of pediatric
      pleural infection. Controversy surrounds its comparative benefits over
      intrapleural fibrinolysis in early exudative or fibrinopurulent pleural empyema
      and its usefulness in the treatment of chronic pleural empyema.

PMID- 12055400
TI  - Proceedings of the 8th International Consensus Conference on Ambulatory Blood
      Pressure Monitoring. Sendai, Japan, 28-30 October 2001.

PMID- 12055398
TI  - Postpneumonectomy empyema.
AB  - Empyema is a serious complication after pneumonectomy. It is often associated
      with a bronchopleural fistula. Several risk factors have been associated with an
      increased incidence of these two challenging complications. Therapy aims at
      simultaneously treating the infected pleural space and the fistula. The authors
      describe their favorite methods which include repeated open debridements of the
      pleural space, primary closure of the fistula, and covering of the bronchial
      stump using intrathoracic transposition of extrathoracic skeletal muscle followed
      by delayed closure of the chest wall after instillation of an antibiotic solution
      (Clagett and modified Clagett procedures). The goals of treatment remain a
      healthy patient with a healed chest wall and no evidence of drainage or
      infection. Excellent results can be obtained in more than 80% of patients.
      Failure is often associated with a persistent or recurrent bronchopleural
      fistula.

PMID- 12055401
TI  - Validation up-date.
AB  - With the increasing marketing of automated and semi-automated devices for the
      measurement of blood pressure, there is a need for potential purchasers to be
      able to satisfy themselves that such devices have been evaluated according to
      agreed criteria. Since their introduction a large number of blood pressure
      measuring devices have been evaluated according to one or both protocols.
      However, experience has demonstrated that the conditions demanded by the
      protocols are extremely difficult to fulfil. The European Society of Hypertension
      (ESH) protocol, named the International Protocol, which will be published
      shortly, is based on the data from 19 validation studies performed according to
      the AAMI and BHS protocols. Critical assessment of this data base of evidence has
      permitted rationalisation and simplification of validation procedures without
      loosing the merits of the much more complicated earlier protocols. This has been
      achieved by elimination of pre-validation phases, improving observer recruitment
      and training, minimising observer error during validation, reducing the number of
      subjects recruited, relaxing the range of blood pressures required and
      eliminating 'hopeless' devices early in the validation procedure.

PMID- 12055402
TI  - State of the market for devices for blood pressure measurement.
AB  - There is a large market for blood pressure measuring devices, not only in
      clinical medicine, but also with the public where the demand for self-measurement
      of blood pressure is growing rapidly. For the consumer, whether medical or lay,
      device accuracy should be of prime importance in selecting a blood pressure
      measuring device. However, the majority of devices available have not been
      evaluated independently for accuracy. In this paper the published evidence for
      independent validation is reviewed and it is recommended that such reviews should
      be undertaken regularly by international bodies, such as the European Society of
      Hypertension.

PMID- 12055403
TI  - Oscillometric blood pressure measurement: progress and problems.
AB  - Oscillometric blood pressure measurement has become very popular, but although a
      number of devices have now passed both the Association for the Advancement of
      Medical Instrumentation and British Hypertension Society criteria, complacency
      with the state of the technique is as yet premature. In individual subjects, a
      substantial number of readings may deviate more than a clinically relevant 5 mmHg
      in devices that have earned a British Hypertension Society grade A rating. The
      marketing of pressure-wave-simulating devices is a welcome development as
      monitors can now be tested for reproducibility; an intra-device standard
      deviation of less than 2 mmHg has been proposed as the limit. Authors suggest
      that these simulators are currently better suited to intra- than between-device
      testing since they are not yet fully confident that the simulated waveforms are
      indistinguishable from the man-made pressure waves. Simulators should, however,
      be incorporated into our standard validation protocols in order eventually to
      obviate the human, fallible, factor in the validation protocols. The currently
      employed maximal amplitude algorithm has many drawbacks as the parameter
      identification points for systolic and diastolic pressure depend on many factors,
      for example pulse pressure, heart rate and arterial stiffness. These errors have
      now been demonstrated in clinical studies. Modern pattern recognition algorithms
      are being constructed but have not yet produced convincing results. As repeatedly
      stated, the development of a more robust and more widely applicable algorithm
      than the maximal amplitude approach should be allocated a high priority.

PMID- 12055404
TI  - Reliability of ambulatory blood pressure monitoring.
AB  - OBJECTIVE: To focus on the reliability of ambulatory blood pressure monitoring
      and on its limitations in clinical practice, and to construct adequate strategies
      to improve ambulatory monitoring performance. METHODS: The literature was
      reviewed, and personal data were used. DISCUSSION: Since the beginning of non
      invasive ambulatory blood pressure monitoring, it appeared that some subjects had
      a high proportion of outlying readings that were unlikely to be accurate.
      Although ambulatory blood pressure is more reproducible than clinic blood
      pressure, large day-to-day differences have also been reported in reproducibility
      studies for average 24 h blood pressure. It has been shown that, for day-to-day
      24 h blood pressure differences greater than 4/3 mmHg, ambulatory blood pressure
      is poorly predictive of the degree of target organ damage. The variability of
      average 24 h blood pressure may arise from several causes, including true
      biological variability, a lack of standardization of activities and measurement
      errors. Artefactual readings can easily occur if patients are not properly
      instructed. Although editing procedures can eliminate outliers, it is often
      impossible to identify inaccurate readings included within the patient's trend.
      To optimize ambulatory blood pressure monitoring, health-care providers should be
      instructed adequately on how to perform this technique. Appropriate patient
      selection, a proper application of instrumentation and the checking of its
      performance, careful instructions to patients, the immediate evaluation of the
      patient's diary and 24 h tracing after completion of the recording should improve
      the results of ambulatory monitoring. CONCLUSIONS: A checklist of criteria that
      should be used for optimizing ambulatory monitoring in clinical practice should
      be proposed by the Consensus Conference on ambulatory blood pressure monitoring.
      To improve doctors' proficiency, strategies including educational protocols and
      training programmes should be implemented.

PMID- 12055405
TI  - Recent advances in blood pressure measurement technology: normalized blood
      pressure measurement with a double-cuff sphygmotonometer.
AB  - BACKGROUND: In our previous studies of 24-h blood pressure measurement, basal
      blood pressure (minimum sleep-time blood pressure) showed the strongest
      correlation with hypertensive target-organ damage. We have currently devised a
      new accurate method of blood pressure measurement that entails recording casual
      blood pressure waves by means of a double-cuff sphygmotonometer, and attempted to
      normalize casual blood pressure to basal blood pressure. METHODS: The double-cuff
      sphygmotonometer records the arterial pressure wave, from which, using the
      formula (P0 = phi(-1)(i) x Pi), we attempted a normalization of casual blood
      pressure (Pi) to values close to those of the basal blood pressure (P0). True
      basal blood pressure was measured by an indirect ambulatory blood pressure
      monitoring device (TM2425, A&D Co. Ltd., Tokyo, Japan). The subjects were 54
      normotensive volunteers and 156 out-patients with essential hypertension [63 with
      World Health Organization (WHO)-II stage and 93 with WHO-I stage, including 47
      subjects with white-coat hypertension] not receiving medication. RESULTS: The
      coefficient of correlation (r) between normalized diastolic blood pressure (Pd0')
      and true diastolic basal blood pressure (Pd0) was 0.82 (mean difference = 1 +/-
      9.8 mmHg), that between normalized systolic blood pressure (Ps0') and true
      systolic basal blood pressure (Ps0) being 0.78 (1 +/- 13 mmHg) in 210 subjects.
      When an office mean blood pressure (MBP) of 116 mmHg was taken as the standard
      for identifying the WHO-I group, the sensitivity was 70% (65/93) and the
      specificity 67% (42/63), but when an MBP0 [MBP0' = (Ps0'-Pd0')/3 + Pd0'] of 89
      mmHg was the standard, the sensitivity was 82% (76/93) and the specificity 90%
      (57/63), both significantly higher than the corresponding values for office MBP
      (P < 0.05). CONCLUSION: We devised a new double-cuff sphygmotonometer and
      normalizing function (phi(-1)) and, using these methods, calculated the
      normalized blood pressure in hypertensive out-patients, which may make it
      possible to identify degrees of severity of hypertension in terms of WHO stages.

PMID- 12055406
TI  - The Japan Home-health Apparatus Industrial Association: investigation of home-use
      electronic sphygmomanometers.
AB  - The Japanese Home-health Apparatus Industrial Association is an official
      independent organization comprising ten departments. That concerned with home
      electronic sphygmomanometers, which has seven participants from different
      Japanese manufacturers, has already undertaken and is currently involved in
      various activities related to voluntary standards for performance validation and
      quality assurance. Because Japanese companies form a large proportion of
      manufacturers, these activities are important in terms of autonomic regulation.
      Although many improvements have been made to home electronic sphygmomanometers,
      some problems still remain unresolved, especially in terms of measurement
      reliability and easy operation by lay people. Another aspect of the department's
      work relates to making proposals on major validation standards, such as those of
      the Association for the Advancement of Medical Instrumentation, the British
      Hypertension Society and Comite Europeen de Normalisation (CEN). Clinical
      validation should be discussed in order to define a more accurate standard method
      of measurement using auscultation and more appropriate criteria that are
      unaffected by primary blood pressure variation.

PMID- 12055407
TI  - Assessment of antihypertensive activity in the regulatory setting.
AB  - Before a new antihypertensive drug receives regulatory approval, it must
      demonstrate a significant blood pressure-lowering effect over its entire dosing
      interval. The Food and Drug Administration recognizes several different methods
      for demonstrating antihypertensive activity, the gold standard continuing to be
      the office/casual blood pressure at the end of the dosing interval (trough).
      There should be at least two studies demonstrating a significant antihypertensive
      effect, at least one of which should include a placebo. Data obtained using
      ambulatory blood pressure monitoring are used for showing the time-course of the
      antihypertensive effect, particular attention being given to possible marked
      differences between the drug's maximum (peak) effect and its activity during the
      trough. In Europe, the Committee for Proprietary Medicinal Products also
      considers the office/casual blood pressure at trough to be a primary measure of
      outcome, responder rates using office/casual readings also being noted. The
      Committee recommends that data be obtained using ambulatory blood pressure
      monitoring in order to demonstrate a drug's antihypertensive activity. In
      addition, it specifically requests that a trough : peak ratio be calculated,
      whereas the Food and Drug Administration does not require this information.

PMID- 12055408
TI  - Task Force I: methodological aspects of blood pressure measurement.
AB  - OBJECTIVE: To reach a consensus on important methodological aspects of blood
      pressure measurement. METHODS: A Task Force on the methodological aspects of
      blood pressure measurement wrote this review after the Eighth International
      Consensus Conference on Blood Pressure Monitoring, in Sendai, Japan (28-31
      October 2001). This consensus paper is based on the papers presented by Task
      Force I and on the discussion sessions, and is therefore representative of a
      broad spectrum of expert opinion. POINTS OF CONSENSUS: Consensus was reached on
      the following five issues: (1) there is an urgent need for a simplified protocol
      for the validation of blood pressure measuring devices; (2) there is a need for a
      means of updating the "state of the market" for validated devices so that users
      can have easy access to this information; (3) new devices must be validated
      independently, and existing devices that have not been validated must be
      reappraised; (4) manufacturers should confirm when new models use algorithms
      which have been validated previously; (5) the Food and Drug Administration now
      accepts that when ambulatory blood pressure measurement is used in clinical short
      term trials in which side-effects are not being assessed, a placebo arm is not
      required.

PMID- 12055409
TI  - Overview of ambulatory blood pressure monitoring in childhood and pregnancy.
AB  - Despite the fact that the study and applicability of ambulatory blood pressure in
      children and pregnant women share characteristics which limit the potential
      development of knowledge for their use, advances produced in the last few years
      provided the present knowledge regarding the significance and the potential use
      of ambulatory blood pressure in children and in the pregnant women. In children
      ambulatory blood pressure monitoring is useful for the diagnosis of mild
      hypertensives, assessment of refractory hypertension, therapeutic trials with
      antihypertensive drugs, and clinical investigation when BP is one of the
      parameters to be taken into account and/or when subtle BP abnormalities are the
      objective of the study. In pregnant women, the main applicability is to assess
      the maternal and fetal risk in the hypertensive disorders of pregnancy.

PMID- 12055410
TI  - Reference values for ambulatory blood pressure and self-measured blood pressure
      based on prospective outcome data.
AB  - Although self-measured blood pressure and ambulatory blood pressure are widely
      used for research and clinical purposes, reference values are still scarcely
      supported by prospective outcome data. For self-measured blood pressure, values
      of 135 mmHg systolic and 85 mmHg diastolic (an average of two measurements in the
      morning and an additional two in the evening for at least 3 working days) have
      been suggested as the upper-normal reference limits. Unfortunately, these values
      have received limited support because only one study, the Ohasama study, examined
      the prognostic value of self-measured home blood pressure. For non-invasive 24 h
      ambulatory blood pressure, there are at least 11 reports of prospective outcome
      studies from independent centres that have examined the prognostic values of
      ambulatory blood pressure, but not all have attempted to define reference values.
      Currently, an average daytime blood pressure of less that 135 mmHg systolic and
      less than 85 mmHg diastolic is generally considered to be normal, and a level
      below 130/80 mmHg may be considered optimal. A reduction in blood pressure of
      less than 10% from day to night identifies subjects with an increased
      cardiovascular risk. There is some evidence that cardiovascular risk is further
      increased when night-time blood pressure is higher than daytime blood pressure.
      An average 24 h pulse pressure of over 53 mmHg identifies subjects with a raised
      cardiovascular risk.

PMID- 12055411
TI  - Assessment of outcomes other than systolic and diastolic blood pressure: pulse
      pressure, arterial stiffness and heart rate.
AB  - In recent years, studies have shown that parameters derived from the arterial
      pressure wave other than systolic and diastolic blood pressure provide important
      information on cardiovascular status. Among these parameters, pulse pressure,
      arterial stiffness and heart rate have emerged as independent markers of
      cardiovascular risk in different populations. Although a number of studies have
      used casual measurements of these parameters in a clinic setting, others have
      focused on their assessment under ambulatory conditions. The pulse pressure
      represents the amplitude of the pressure wave signal (systolic minus diastolic
      blood pressure), higher pulse pressure values having been reported in patients
      possessing cardiovascular risk factors. Close associations between a high pulse
      pressure and several surrogate end-points have been described. Furthermore,
      epidemiological studies have shown that a high pulse pressure is an independent
      predictor of hard end-points in several populations. Arterial stiffness
      represents one of the major haemodynamic factors determining pulse pressure.
      Pulse wave velocity, measured from the initial upstroke of the pressure wave,
      constitutes an established index of arterial stiffness. Studies have reported
      stiffer arteries in patients with cardiovascular pathology even at an early stage
      of disease. Close correlations between arterial stiffness and several surrogate
      markers have been reported, and arterial stiffness and its changes have recently
      been shown to be an independent predictor of hard end-points in patients with a
      high cardiovascular risk. Methods to evaluate arterial stiffness under ambulatory
      conditions are emerging. Heart rate represents the frequency of the cyclical
      strain of the arterial wall, clinical studies having shown that ambulatory heart
      rate is correlated to several surrogate markers. A few epidemiological studies
      have analysed the value of ambulatory heart rate as an independent predictor of
      hard end-points, but their positive findings need to be confirmed. The analysis
      of the pressure wave thus allows the determination of several haemodynamic
      indices other than systolic and diastolic blood pressure. Pulse pressure,
      arterial stiffness and heart rate constitute other outcomes that may be useful as
      additional factors in risk assessment for future therapeutic decision-making.

PMID- 12055412
TI  - Predictive values of automated blood pressure measurement: what can we learn from
      the Japanese population - the Ohasama study.
AB  - BACKGROUND: Measurements of ambulatory blood pressure (ABP) and of home blood
      pressure (HBP) as an adjunct to casual/clinic blood pressure (CBP) measurements
      are currently widely used for the diagnosis and treatment of hypertension. We
      have monitored a rural cohort of people from the population of Ohasama, Japan,
      with respect to their prognosis and have previously reported that ABP and HBP are
      superior to CBP for the prediction of cardiovascular mortality. One reason that
      CBP is a poor predictor of prognosis is that it incorporates several biases,
      including the white-coat effect. METHODS AND RESULTS: We examined the prognostic
      significance of white-coat hypertension for mortality and found that the relative
      hazard for the overall mortality of patients with white-coat hypertension was
      significantly lower than that for true hypertension. Short-term blood pressure
      variability has recently attracted attention as a cause of target-organ damage
      and cardiovascular complications. Our results confirmed that short-term blood
      pressure variability (as measured every 30 min) was independently associated with
      cardiovascular mortality. In addition, research has recently focused on isolated
      systolic hypertension and pulse pressure as independent risk factors for poor
      cardiovascular prognosis. The Ohasama study also clearly demonstrated that
      isolated systolic hypertension and increased pulse pressure, as assessed by HBP,
      were associated with an increase in the risk of cardiovascular mortality.
      Circadian blood pressure variation is characterized by a diurnal elevation and a
      nocturnal decline in blood pressure. We therefore compared morbidity from stroke
      between dippers (subjects who show an ordinal nocturnal dipping of blood
      pressure) and non-dippers (those with a diminished nocturnal dipping or nocturnal
      elevation of blood pressure [inverted dippers]) in the Ohasama study. The
      incidence of stroke increased with an increased length of observation in dippers
      using antihypertensive medication but not in non-dippers using antihypertensive
      medication. In contrast, the relative hazard for mortality increased in non
      dippers and inverted dippers. These results suggest a cause-and-effect
      relationship for both dippers and non-dippers. CONCLUSION: The Ohasama study
      showed that the level and variability of hypertension as assessed by ABP and HBP
      are independent predictors of cardiovascular mortality. It also demonstrated an
      independent association between the prognosis of hypertension and each component
      of ABP and HBP, indicating the prognostic significance of these blood pressure
      measurements.

PMID- 12055413
TI  - Blood pressure variability as a risk factor.
AB  - Blood pressure variability is clinically relevant because of the evidence that
      the degree of blood pressure fluctuation may independently contribute to organ
      damage and to the cardiovascular risk of hypertensive patients. This review will
      focus on the evidence available to support this concept. As such, data obtained
      from cross-sectional studies, longitudinal studies in humans and experimental
      studies in animals will be discussed. The possibility of antagonizing an
      excessive degree of blood pressure variability by administering drugs to provide
      a long-lasting and smooth antihypertensive action will also be discussed, as will
      the usefulness of mathematical indices aimed at quantifying the homogeneity of
      the blood pressure reduction by treatment.

PMID- 12055414
TI  - Early morning surge in blood pressure.
AB  - Early-morning blood pressure is generally viewed as an important therapeutic
      target, for two reasons. First, for antihypertensive agents taken once daily in
      the morning, the timing of the trough plasma drug level, and thereby the lowest
      pharmacodynamic effect, often coincides with the early morning rise in blood
      pressure and heart rate. Evidence has been accumulated to suggest that blood
      pressure control throughout the 24 h period may be necessary to gain complete
      benefit from antihypertensive medication. In fact, in a longitudinal study, the
      regression of cardiac hypertrophy in patients with hypertension was more
      accurately predicted by treatment-induced changes in average 24 h ambulatory
      blood pressure than by clinic or home-monitored blood pressure readings. The
      other reason for the importance of morning blood pressure is that cardiovascular
      risk is heightened at this time of day. A morning surge in sympathetic activity
      alters haemodynamic forces and predisposes vulnerable coronary atherosclerotic
      plaques to rupture. At the same time as this risk of plaque rupture is greatest,
      circadian variations in haemostatic and fibrinolytic factors result in morning
      hypercoagulability and hypofibrinolysis, promoting the formation of intraluminal
      thrombi. We recently showed that, in older hypertensives, a greater morning blood
      pressure surge, mediated at least in part by an exaggerated alpha-sympathetic
      activity, is associated with more advanced silent cerebrovascular disease as well
      as a higher future incidence of stroke. The early morning surge in blood pressure
      could become a new therapeutic target for preventing target-organ damage and
      subsequent cardiovascular events in hypertension. Of greatest interest is the
      potential benefit of a chronotherapeutic approach, involving, for example, long
      acting chronoformulations, which has not yet been extensively studied.

PMID- 12055415
TI  - Task Force II: blood pressure measurement and cardiovascular outcome.
AB  - OBJECTIVE: To reach a consensus on the prognostic significance of new techniques
      of automated blood pressure measurement. METHODS: A Task Force on the prognostic
      significance of ambulatory blood pressure monitoring wrote this review in
      preparation for the Eighth International Consensus Conference (28-31 October
      2001, Sendai, Japan). This synopsis was amended to account for opinions aired at
      the conference and to reflect the common ground reached in the discussions.
      POINTS OF CONSENSUS: (1) Prospective studies in treated and untreated
      hypertensive patients and in the general population have demonstrated that, even
      after adjusting for established risk factors, the incidence of cardiovascular
      events is correlated with blood pressure on conventional as well as ambulatory
      measurement. Ambulatory monitoring, however, significantly refines the prediction
      already provided by conventional blood pressure measurement. (2) White-coat
      hypertension is usually defined as an elevated clinic blood pressure in the
      presence of a normal daytime ambulatory blood pressure. Event-based studies in
      hypertensive patients have convincingly demonstrated that the risk of
      cardiovascular disease is less in patients with white-coat hypertension than in
      those with higher ambulatory blood pressure levels even after controlling for
      concomitant risk factors. Based on prognostic evidence, white-coat hypertension
      can now be defined as a conventional blood pressure that is persistently equal to
      or greater than 140/90 mmHg with an average daytime ambulatory blood pressure of
      below 135/85 mmHg. The issue of whether or not white-coat hypertension
      predisposes to sustained hypertension needs further research. (3) There is a
      growing body of evidence showing that a decreased nocturnal fall in blood
      pressure (<10% of the daytime level) is associated with a worse prognosis,
      irrespective of whether night-time dipping is studied as a continuous or a class
      variable. (4) Intermittent techniques of ambulatory blood pressure monitoring are
      limited in terms of quantifying short-term blood pressure variability. Proven
      cardiovascular risk factors such as old age, a higher than usual blood pressure
      and diabetes mellitus are often associated with greater short-term blood pressure
      variability. After adjusting for these risk factors, some - but not all - studies
      have nevertheless reported an independent and positive relationship between
      cardiovascular outcome and measures of variability of daytime and night-time
      blood pressure, for example standard deviation. (5) Reference values for
      ambulatory blood pressure measurement in children are currently based on
      statistical parameters of blood pressure distribution. In children and
      adolescents, functional rather than distribution-based definitions of ambulatory
      hypertension have yet to be developed. (6) Several studies of gestational
      hypertension have shown that, compared with office measurement, ambulatory blood
      pressure monitoring is a better predictor of maternal and fetal complications.
      Pregnancy is a special indication for ambulatory monitoring so that the white
      coat effect can be measured and pregnant women are not given antihypertensive
      drugs unnecessarily. (7) Ambulatory pulse pressure and the QKD interval are
      measurements obtained by ambulatory monitoring that to some extent reflect the
      functional characteristics of the large arteries. The QKD interval is correlated
      with left ventricular mass, and ambulatory pulse pressure is a strong predictor
      of cardiovascular outcome. (8) Under standardized conditions, the self
      measurement of blood pressure is equally as effective as ambulatory blood
      pressure monitoring in identifying the white-coat effect, but further studies are
      required to elucidate fully the prognostic accuracy of self-measured blood
      pressure in comparison with conventional and ambulatory blood pressure
      measurement. CONCLUSIONS: Ambulatory blood pressure measurement refines the
      prognostic information provided by conventional blood pressure readings obtained
      in the clinic or the doctor's office. Longitudinal studies of patients with white
      coat hypertension should clarify the transient, persistent or progressive nature
      of this condition, particularly in paediatric patients, in whom white-coat
      hypertension may be a harbinger of sustained hypertension and target-organ damage
      in adulthood. Finally, the applicability, cost-effectiveness and long-term
      prognostic accuracy of the self-measurement of blood pressure should be evaluated
      in relation to conventional blood pressure measurement and ambulatory monitoring.

PMID- 12055416
TI  - Reproducibility and cost of blood pressure self-measurement using the 'Loaned
      Self-measurement Equipment Model'.
AB  - OBJECTIVE: To determine the reproducibility and the cost of the Loaned Self
      measurement Equipment Model for blood pressure. SUBJECTS: Seventy-five subjects
      with non-complicated essential hypertension, having an average age of 56.2 +/- 11
      years, were evaluated. METHODS: The Loaned Self-measurement Equipment Model
      consists of a set of sphygmomanometers belonging to the clinic, loaned to
      patients for 3-day periods for them to carry out 27 readings, and then returned.
      Using a mercury sphygmomanometer, a nurse carried out office blood pressure
      readings during two visits. A month later, the same procedure was repeated under
      the same clinical conditions. The agreement between studies was assessed by
      correlation coefficients, coefficients of variation and standard deviation of the
      differences (SDD). RESULTS: The office blood pressure was 147 +/- 17/89 +/- 12
      mmHg during visit A, and 145 +/- 16/88 +/- 11 mmHg during visit B. The self
      measurement blood pressure was 139 +/- 16/84 +/- 10 mmHg during the first visit,
      and 136 +/- 15/84 +/- 11 mmHg during the second visit. In neither of the cases
      were the differences statistically significant. The correlation coefficients for
      the office and self-measurement systolic blood pressure were statistically
      significant (P = 0.018), while those for the diastolic blood pressure were not
      statistically significant. The SDD for self-measurement systolic blood pressure
      was 10.7, compared to 15.0 for the office blood pressure (P < 0.01). The
      comparison in the case of diastolic blood pressure was not significant. The cost
      of each loan was $5.85 (US dollars). CONCLUSIONS: The Loaned Self-measurement
      Equipment Model has a good short-term reproducibility, and the cost is
      reasonable.

PMID- 12055417
TI  - Arterial elasticity among normotensive subjects and treated and untreated
      hypertensive subjects.
AB  - OBJECTIVE: The aim of this study was to determine arterial elasticity in
      normotensive and hypertensive individuals. BACKGROUND: In addition to blood
      pressure, other parameters serve as markers for vascular disease. Arterial
      elasticity is one parameter that can be determined by a modified Windkessel model
      of the circulation. This model estimates, from a computerized pulse contour
      analysis, the proximal (capacitive) elasticity of the large arteries and the
      distal (reflective) elasticity of the small arteries. METHODS: A prospective,
      multi-center, controlled clinical study evaluated large-artery and small-artery
      elasticity indices in four groups: (1) normotensives without a family history of
      hypertension; (2) normotensives with a family history of hypertension; (3)
      treated and controlled hypertensives; and (4) untreated and uncontrolled
      hypertensives. Blood pressure, using a mercury manometer, and arterial
      elasticity, using a CVProfilor DO-2020 CardioVascular Profiling System
      (Hypertension Diagnostics, Inc., Eagan, MN, USA), were measured supine in
      triplicate 3 min apart in a randomized sequence. RESULTS: There were 212
      evaluable subjects of mean age 46 years; 57% were women, 51% Caucasian and 33%
      African-American. Comparing normotensives without a family history and untreated
      hypertensives, both large-artery and small-artery elasticity indices were
      significantly different (P < 0.0001). After controlling for age and body surface
      area, a significant linear trend (P = 0.0001) across the four groups was detected
      for both large- and small-artery elasticity indices. CONCLUSION: As the
      hypertension status worsened, large- and small-artery elasticity indices
      decreased, suggesting a potential for the diagnostic use of arterial elasticity
      determinations.

PMID- 12055418
TI  - Clinic and ambulatory heart rate in sustained and white-coat hypertension.
AB  - BACKGROUND: Sustained and white-coat hypertensives show hypertension in the
      office setting but different blood pressure values outside the clinical
      environment. So far, only a few incomplete data on heart rate are available
      inside and outside the clinical setting in these groups of patient. The aim of
      this study was to evaluate clinic and ambulatory heart in sustained
      hypertensives, white-coat hypertensives and normotensives. METHODS: We selected
      236 sustained hypertensives, 236 white-coat hypertensives and 236 normotensives
      matched for age, gender and body mass index, and with a similar occupation. The
      subjects had been submitted to clinic evaluation and the non-invasive monitoring
      of blood pressure and heart rate. White-coat hypertension was defined as clinic
      hypertension and a daytime blood pressure of less than 135/85 mmHg. RESULTS: The
      clinic heart rate was significantly higher in sustained hypertensives and white
      coat hypertensives than in normotensives (76 +/- 11 versus 75.5 +/- 10 versus 70
      +/- 9 beats/min [bpm], respectively, P < 0.05). The daytime heart rate was
      significantly higher in sustained hypertensives than in white-coat hypertensives
      and normotensives (79.4 +/- 10 versus 74.6 +/- 8.5 versus 74.5 +/- 8.5 bpm,
      respectively, P < 0.05), as were the night-time heart rate (67 +/- 8.5 versus 63
      +/- 8 versus 63 +/- 8 bpm, respectively, P < 0.05) and 24 h heart rate (76.3 +/-
      9 versus 72 +/- 7.8 versus 72 +/- 8 bpm, respectively, P < 0.05). When men and
      women were analyzed separately, the same trend was observed. CONCLUSIONS: The
      clinic heart rate is similar in sustained and white-coat hypertensives, but the
      ambulatory heart rate is lower in white-coat hypertensives. As ambulatory heart
      rate is more representative of 24 h heart rate load and may be a better indicator
      of the detrimental effect of heart rate, our findings suggest that white-coat
      hypertensives are at lower cardiovascular risk than sustained hypertensives.

PMID- 12055419
TI  - Association of urinary albumin concentration with casual and ambulatory blood
      pressure: a similar relationship in normotensive and hypertensive subjects.
AB  - BACKGROUND: The urinary albumin level has been found to be positively correlated
      with blood pressure in hypertensive patients. To our knowledge, this relationship
      has not been evaluated in normotensive subjects and compared with that in
      hypertensives using casual and ambulatory blood pressure measurements. METHODS:
      In this cross-sectional study, a cohort of 234 normotensive and hypertensive
      participants wore an ambulatory blood pressure monitor for 24 h, standardized
      casual blood pressure measurements being taken. The urinary albumin concentration
      was determined by the dipstick Micral Test. The bivariate and multivariate
      relationship between urinary albumin concentration and demographic and blood
      pressure measures was investigated using correlational and regression analyses.
      RESULTS: The prevalence of microalbuminuria was significantly greater in the
      hypertensive than normotensive participants. The urinary albumin concentration
      was positively associated with both casual and ambulatory measures of blood
      pressure in both the normotensive and hypertensive subsamples, stronger
      correlations being found for systolic blood pressure. The relationship between
      systolic blood pressure and urinary albumin concentration was similar in the
      normotensive and hypertensive subsamples. CONCLUSIONS: These findings confirm
      earlier reports of the greater prevalence of microalbuminuria in patients with
      hypertension than in normotensive participants, as well as those reporting a
      continuous relationship in hypertensive participants. This study extends prior
      research to a normotensive subsample, in whom a similar relationship of blood
      pressure to microalbuminuria, using both ambulatory and casual measures of blood
      pressure, was found. Future research should investigate the causal direction of
      this relationship.

PMID- 12055420
TI  - 24 h non-invasive ambulatory blood pressure monitoring: do the number of
      recordings per hour and/or ways of analyzing day and night matter?
AB  - OBJECTIVE: To analyze whether the number of blood pressure registrations per hour
      and/or different ways of defining day and night have any influence on the result
      of ambulatory blood pressure monitoring. DESIGN AND METHODS: The study used blood
      pressure data from 40 normotensive subjects (20 men) and 40 (20 men) treated
      hypertensive patients who had undergone 24 h non-invasive ambulatory blood
      pressure monitoring twice (on a work day and a non-work day), three recordings
      per hour being made. Calculations were made based on all recordings and with one
      and two recordings per hour randomly removed. The definition of night was the
      subject's own (from going to bed until getting up), and an arbitrary designation
      of 2200 h-0600 h. RESULTS: The mean blood pressure (systolic/diastolic and
      standard deviation) over 24 h showed no significant difference between
      calculations based on three, two or one blood pressure registrations per hour in
      either hypertensives or normotensives, nor was there any significant difference
      when the same kind of calculation for day and night was made based on the
      subject's own statement or on arbitrary dividing lines. The between-patient
      standard deviation increased, albeit marginally, with fewer registrations.
      Individual comparisons revealed a difference over 24 h of 8.4/6.7 mm Hg between
      three and one registrations per hour in one hypertensive patient during a non
      work day. All the others had lesser and very small differences. CONCLUSION: An
      analysis of our data revealed no major differences in mean blood pressure if one,
      two or three recordings per hour were used. Arbitrary dividing lines for day and
      night or according to the individual's own statement did not have any major
      effect on the result. This must be considered to be an advantage when data from
      different studies are compared or pooled. It may, however, be wise to perform
      recordings no less than every 30 min when evaluating individual patients.

PMID- 12055421
TI  - How should we measure blood pressure in the doctor's office?
AB  - BACKGROUND: Blood pressure is the most ubiquitous diagnostic recording made in
      the doctor's office, but the measurement is subject to a number of sources of
      bias, which may lead to over- or underestimation. The current study examined the
      systematic influence of the way in which the measurements were taken - by the
      physician, by a nurse, or with the patient sitting alone, using an automated
      device. SUBJECTS AND METHODS: Blood pressure was measured in 17 essential
      hypertensive and 10 white-coat hypertensive individuals. On separate clinic
      visits, measurements were taken by the attending physician, by a nurse and using
      an automated device (Arteriosonde 1216). RESULTS: A repeated-measures ANOVA
      revealed that, for systolic pressure, there was a significant effect of
      measurement modality on blood pressure. Physician systolic pressures were on
      average approximately 10 mmHg higher than those taken by a nurse, nurse pressures
      being approximately 7 mmHg higher than those recorded using Arteriosonde. The
      effect on diastolic pressure was similar but smaller, and no nurse-Arteriosonde
      difference was observed. CONCLUSIONS: We conclude that the routine clinical
      assessment of blood pressure would be more representative of daily ambulatory
      pressure if an automated device, without doctor or nurse present, were used.

PMID- 12055422
TI  - Ambulatory blood pressure monitoring in children with a solitary kidney - a
      comparison between unilateral renal agenesis and uninephrectomy.
AB  - BACKGROUND: In experimental animals, a reduction in renal mass leads to
      glomerulosclerosis of the residual parenchyma and eventual renal failure. In
      humans, however, data on the influence of nephrectomy or agenesis on future
      functional parameters and hypertension are as yet controversial. OBJECTIVE: To
      evaluate blood-pressure patterns in children with a solitary kidney as a result
      of either unilateral renal agenesis (URA) or uninephrectomy (UNX) and correlate
      them to the increase in size of the remaining kidney. METHODS: Twenty-eight
      children with a solitary kidney were divided into two groups: the URA group, with
      18 subjects (13 male and five female, with a mean age of 9.6 +/- 3.9 years), and
      the UNX group, which contained 10 subjects (four male and six female, with a mean
      age of 14.0 +/- 2.7 years). The mean time since nephrectomy was 8.7 years. Each
      study group was assigned an age-, weight- and height-matched control group. In
      all subjects, ambulatory blood pressure monitoring was performed using the
      SpaceLabs model no. 90207. Daytime and night-time were defined as 0800-2200 h and
      2200-0800 h, respectively. Urinalysis, serum creatinine and urea results were
      recorded for all the study group participants. The size of the remaining kidney
      was determined by ultrasound examination. The percentage increase in kidney size,
      as calculated from standard kidney-length-against-age nomograms was correlated to
      the percentage deviation from normal blood pressure values. RESULTS: The mean 24
      h, daytime and night-time systolic blood pressure (SBP) readings were
      significantly higher in children in the URA group than in those in the
      corresponding control group (111.4 +/- 7.5 mmHg versus 106.9 +/- 6.7 mmHg, P <
      0.004; 115.2 +/- 3.1 mmHg versus 110.7 +/- 3.4 mmHg, P < 0.004; and 105.2 +/- 2.6
      mmHg versus 101.2 +/- 1.8 mmHg, P < 0.002, respectively). Daytime heart rate was
      found to be significantly reduced (84.4 +/- 5.2 versus 87.8 +/- 8.2 beats/min, P
      < 0.04). In the UNX group, 24 h mean, systolic and diastolic blood pressure
      (DBP), as well as heart rate, did not differ from control values. Daytime
      systolic and diastolic blood pressures were higher than those of the controls
      (119.8 +/- 4.0 mmHg versus 115.5 +/- 3.8 mmHg, P < 0.02; and 72.7 +/- 4.0 mmHg
      versus 70.0 +/- 11.0 mmHg, P < 0.02, respectively). Nocturnal dipping was present
      in all groups and was of equal magnitude in the corresponding control groups. The
      mean 24 h diastolic blood pressure load was significantly greater in URA patients
      than in controls (19.6 versus 10.8%, respectively, P < 0.01). In the UNX group,
      the blood pressure loads were similar to those of controls. The percentage
      increase in length of the remaining kidney was found to correlate positively with
      the percentage delta increase in both systolic and diastolic blood pressure.
      CONCLUSIONS: Compared with the age-, height- and weight-matched controls, the
      children with a solitary kidney caused by URA had an elevated mean 24 h SBP. In
      contrast, those with UNX had mean 24 h blood pressure values similar to those of
      their controls. A rise in SBP was, however, seen in both groups during the
      daytime hours. Thus, the presence of a solitary kidney, for whatever reason, may
      be pathogenetically linked to a raised blood pressure, and this linkage may be
      more pronounced in URA. The delta increase in size of the remaining kidney may
      serve as a prognostic indicator of blood pressure elevation.

PMID- 12055423
TI  - Digital operation notes: a useful addition to the written record.
AB  - The use of photographic images to supplement written records has been used in
      clinical medical practice for many years. The additional information that a
      photograph provides is useful to record pathological findings, anatomic changes,
      surgical relationships, and outcomes. Obtaining relevant, good-quality digital
      images is extremely easy with the new generation of digital camera systems. The
      images obtained are very versatile and can be either printed as hard copies or
      stored in image databases. With the advent of electronic patient records, written
      operation notes can be stored alongside images to give a more complete account of
      a patient's treatment. Networked computer systems allow access to these records
      from a variety of different locations, thereby improving the use of photographs
      by different specialties. The authors encourage intraoperative photography to
      enhance the written operation note and have found it helpful to fellow surgical
      colleagues, pathologists, and physiotherapists in overall patient care.

PMID- 12055424
TI  - Ring avulsion replantation by extended debridement of the avulsed digital artery
      and interposition with long venous grafts.
AB  - Ring avulsion replantation is a technically challenging procedure with a very low
      success rate. Because the zone of arterial injury is more extensive than what it
      appears to be in such avulsion amputations, a technique was developed to debride
      the avulsed digital artery for a long distance, extending well into the digital
      pulp, thereby creating healthy arterial ends to be bridged by one or two segments
      of long venous grafts. Using this technical approach, 7 patients with complete
      amputations of ring avulsion injury (Urbaniak's class III) were operated. In all
      amputations the bone was disrupted at the distal interphalangeal level (except in
      1 patient) and the soft tissues at the proximal phalanx level, with the proximal
      interphalangeal joint and the flexor digitorum superficialis tendons being
      intact. Results indicated that replantation was successful in all patients.
      However, 2 patients presented with unusually late arterial failure 28 and 30 days
      after surgery respectively. Although one of these cases was salvaged by
      reoperation, the other case (followed by conservative management) demonstrated
      partial distal necrosis. Therefore, the ultimate success rate in this series was
      85% in the long term. At follow-up, sensibility was protective in all patients,
      with an average static two-point discrimination of 7.8 mm (range, 6-14 mm). The
      total active motion of the replanted digits was 194 deg on average (range, 155
      205 deg) without loss of function of the proximal interphalangeal joint except in
      2 patients who had late vascular problems. The authors conclude that
      microsurgical replantation of completely amputated ring avulsion injuries with an
      intact proximal interphalangeal joint and flexor digitorum superficialis tendon,
      is a worthwhile procedure that results in good functional and aesthetic results.
      Furthermore, using an aggressive approach for debridement of the avulsed digital
      artery, as described in this article, an experienced microsurgeon can replant
      successfully nearly all cases. However, one should be cautious in the follow-up
      of such patients, because late arterial failure may be encountered, as was
      observed in 2 patients in this series. The authors suggest immediate reoperation
      in such unusual circumstances.

PMID- 12055425
TI  - Phenol cauterization for ganglions of the hand, wrist, and foot: a preliminary
      report.
AB  - Many methods have been reported for the treatment of ganglions. The authors
      present their modified technique for ganglion sclerotherapy. Their modification
      enables them to perform sclerotherapy safely and consistently, and they have
      treated 10 patients in this manner. The method is described and the cases are
      illustrated.

PMID- 12055426
TI  - Complications of the reverse homodigital island flap in fingertip reconstruction.
AB  - Twenty-four digital artery island flaps with reversed flow were used to
      reconstruct 23 patients with fingertip injuries in the authors' clinic between
      June 1998 and August 2000. No nerve coaptation was performed in these patients.
      Patient age ranged between 18 and 35 years. All patients were evaluated at
      clinical follow-up for active range of motion, appearance, patient satisfaction,
      two-point discrimination, hypersensitivity and cold intolerance, previous hand
      injury, and flap viability in the repaired finger. Based on their experience, the
      authors consider that this procedure has several disadvantages: relatively high
      flap loss, sacrifice of one of the two major arteries of the finger, it is a time
      consuming method, it is a difficult flap dissection, there is a requirement for
      loupe and microsurgical equipment. The authors think that this flap should not be
      the first choice for fingertip reconstruction especially for patients who have
      possibility of reinjuring their hands because of their jobs.

PMID- 12055427
TI  - Intrafocal pinning of distal radius fractures: a simplified approach.
AB  - Distal radius fractures are not often treated by plastic surgeons. At the
      authors' institution, plastic surgery manages half of all traumas below the
      elbow, including distal radius and forearm fractures. This opportunity gives the
      residents a unique perspective for comprehensive training in treating upper
      extremity injuries. Because a distal radius fracture is the most common fracture
      of the upper extremity, the authors describe the use of intrafocal pinning as a
      simple and effective approach in the treatment of extra-articular distal radius
      fractures (Colles' fractures). They conducted a prospective study of 18 patients
      with Colles' fractures treated sequentially at their institution from 1998 to
      2001 using this technique. They measured ulnar variance and palmar tilt of the
      distal radius at the time of injury, after closed reduction, immediately
      postoperatively, and 11 weeks postoperatively. Acceptable distal radius reduction
      aims to achieve at least neutral ulnar variance and 0-deg palmar tilt. Compared
      with closed reduction, they achieved superior anatomic reduction with intrafocal
      pinning: ulnar variance, +2.6 mm vs. -1.4 mm; palmar tilt, -13.3 deg vs. +2.1
      deg). These results were stable at the 11-week follow-up. Intrafocal pinning is a
      valuable tool in the management of Colles' fractures. It is simple to perform and
      to teach, and it produces results that are superior to closed reduction alone.

PMID- 12055428
TI  - Free flaps in the treatment of locally advanced malignancy of the scalp and
      forehead.
AB  - Locally advanced cutaneous malignancy of the scalp and forehead is a disease that
      requires an aggressive approach to resection and reconstruction. Free flap
      reconstruction in these sites has been advocated because of the advantages of
      importing large amounts of well-vascularized tissue into a recipient site, which
      has often been compromised by previous surgery or radiotherapy. A consecutive
      series of 32 free flap reconstructions in 29 patients with cutaneous malignancy
      of the scalp and forehead was reviewed. The flap failure rate was 6% (two flaps)
      and the major complication rate was 10%. Of the surviving flaps, 97% (N = 29)
      were successful in reconstructing a challenging group of defects. Three patients
      developed local recurrence of the primary malignancy (mean follow-up, 21 months).
      The use of a broad repertoire of free tissue transfers in reconstruction of the
      scalp and forehead defects has allowed effective treatment of locally advanced
      malignancy of this region. Critical analysis of the results, however, indicates
      that microsurgical reconstruction is not without morbidity and that there are
      refinements in the diagnostic and operative steps of management that can maximize
      the functional and aesthetic results.

PMID- 12055429
TI  - Usefulness of color Doppler sonography for assessing hemodynamics of free flaps
      for head and neck reconstruction.
AB  - This report focuses on the monitoring of intraoperative and postoperative
      hemodynamics of free flaps for repair of head and neck defects by color Doppler
      sonography (CDS). The study group included 20 patients with head and neck cancer
      who underwent resection and reconstruction with free flaps. The hemodynamics in
      the feeding arteries of the flaps were measured during the following six stages:
      before surgery, immediately after microvascular anastomosis, and on postoperative
      days 1, 3, 5, and 7. The pulsatility index (PI) was used as the index for
      measuring changes in hemodynamics over time. Grafts showed the maximal PI
      immediately after vascular anastomosis. PI decreased over 3 to 7 days. Of the 20
      patients, 1 patient in whom the hypopharynx was reconstructed with the radial
      forearm flap developed venous occlusion. This was diagnosed during the early
      stage using CDS, allowing the flap to be saved. CDS proved to be very useful for
      real-time observation of the hemodynamics in free flaps.

PMID- 12055430
TI  - Versatility of scanning laser Doppler imaging to detect cutaneous perforators.
AB  - Several perforator-based flaps have been developed recently and, although
      preoperative evaluation of perforator vessels is important, the conventional
      method using the Doppler flowmeter is still being used. The authors tried to
      identify perforator vessels in the abdominal region using scanning laser Doppler
      imaging and then compared the results with those obtained using an ultrasonic
      Doppler flowmeter in 10 healthy volunteers. The scanning laser Doppler detected
      several perforator vessels (range, 2-5 vessels; mean, 3.1 vessels) within a 7.5 x
      7.5-cm area in the abdominal region. These results suggest that scanning laser
      Doppler imaging is a useful tool in the identification of perforator vessels.

PMID- 12055431
TI  - Silicone migration from silicone-injected breasts: magnetic resonance images.
AB  - Injection of liquid silicone into the breast was performed illicitly in the 1950s
      to 1960s and was subsequently prohibited. Many complications arise from silicone
      injection, and liquid silicone migration is a complication that has not been
      widely reported. The authors present magnetic resonance images of a patient with
      liquid silicone migration from the breast to the upper chest and lower neck.
      Breast ultrasonographic and mammographic findings are also presented for
      correlation.

PMID- 12055432
TI  - Vertical mammaplasty with a clamp technique.
AB  - The vertical mammaplasty with a clamp technique is a personal adaptation of the
      clamp technique that leaves a single vertical scar in addition to the periareolar
      scar. This technique uses a superior pedicle from the dermal vault technique.
      There is no need for preoperative markings. The glandular tissue is removed with
      constant reference to the breast base. The skin is excised around a new clamp,
      which leaves only a vertical scar. This retrospective study includes 100 patients
      operated between 1996 and 2000. A total of 96% of the patients have been happy
      with the final cosmetic result. The best results were obtained when breast ptosis
      and moderate hypertrophy were present. The complication rate was 4%. This
      technique is as reliable as other procedures using the superior flap technique. A
      vertical scar is obtained by using a new clamp that allows a perfect match of the
      gland to its cutaneous cover. It is also a fast technique to perform (75
      minutes).

PMID- 12055433
TI  - Reducing the morbidity from extravasation injuries.
AB  - Extravasation is defined as the leakage of solutions from the vein. This may
      cause damage to surrounding tissue during intravenous fluid administration.
      Extravasation has an incidence of 5% of all cytotoxic drug administrations. In
      the authors' hospital, a protocol has been set up using the dilution flush-out
      technique. Extravasation packs containing cannulae, normal saline, hyaluronidase,
      and instructions on how to manage extravasation injuries, accompanied by an audit
      sheet to assist follow-up, have been introduced to allow the treatment of
      extravasation at the ward level in an attempt to reduce morbidity from the
      injury. Between December 1997 and December 1999, 18 adult patients were
      identified with extravasation injuries after the administration of cytotoxic
      medication. Seventeen were treated immediately according to the protocol. One,
      however, was not. Patients were followed-up for 6 months after injury. The 17
      patients treated immediately needed no further surgical intervention, whereas the
      1 patient not treated needed a split skin graft to cover the defect. The authors
      recommend the placement of "extravasation packs" on all wards where cytotoxic
      drugs are prescribed and that all staff members are familiar with this regime.
      These steps help to reduce the morbidity of a potentially damaging injury.

PMID- 12055434
TI  - Outcomes for surgical coverage of pressure sores in nonambulatory, nonparaplegic,
      elderly patients.
AB  - Pressure sores are a common complication of long-term institutional care.
      Surgical coverage of late-stage ulcers in the elderly refractory to conservative
      therapy remains controversial. The authors reviewed the outcome of 22
      predominately nonambulatory, nonparaplegic, elderly patients with coverage of 27
      pressure sores. The mean patient age was 59 years (range, 50-82 years). The
      average follow-up was 6 months (range, 3 months-2 years). There were 11
      complications for the 22 patients (50%) and the 27 ulcers (41%). Postoperatively,
      a well-healed ulcer was present in 19 of 27 patients (70%) at 6 months. Of the 19
      reconstructed sacral ulcers, there were 10 complications (53%) and one recurrence
      at 6 months. Seven trochanteric ulcers were covered with tensor fascia lata flaps
      without complications or recurrences at the 6-month follow-up. One ischial ulcer
      was managed using a V-Y hamstring advancement flap, resulting in dehiscence and a
      subsequent revision. The authors advocate surgical coverage to treat late-stage
      pressure sores in nonparalyzed elderly persons to reduce the morbidity,
      mortality, and economic burden of patients with late-stage pressure ulcers. With
      an increasing geriatric population, prevention and postoperative care are
      necessary to diminish the incidence, recurrence, and burden of pressure sores.

PMID- 12055435
TI  - Further evidence for the role of fibrosis in the pathobiology of rhinophyma.
AB  - Recent evidence suggests that fibrosis may play an important role in the
      pathobiology of rhinophyma. The fibrogenic cytokine transforming growth factor
      (TGF)-beta2 has been reported to be up-regulated in rhinophyma tissue. Of the
      three common isoforms of TGF-beta, TGF-beta1 and TGF-beta2 are considered
      fibrogenic, whereas TGF-beta3 has antiscarring properties. To provide further
      evidence for the role of fibrosis in the pathobiology of rhinophyma, specimens
      from 8 patients with rhinophyma were compared with nine specimens of normal nasal
      skin. Immunohistochemistry was used to compare intensity levels of TGFbeta1 and
      TGFbeta3 proteins, and quantitative reverse transcription-polymerase chain
      reaction was used to determine messenger ribonucleic acid (mRNA) expression
      levels of TGFbeta1 and TGFbeta3. TGF-beta1 was elevated significantly in
      rhinophyma tissue (p < 0.001), whereas TGF-beta3 was no different in the
      rhinophyma specimens compared with normal nasal skin (p = 0.06). TGFbeta1 mRNA
      expression was five-fold higher in rhinophyma tissue compared with normal skin (p
      < 0.001). The mRNA expression of TGF-beta3 was the same for both pathological and
      normal tissue (p < 0.09). These data, together with previously published
      observations, present further evidence that fibrosis mediated by the fibrogenic
      cytokines TGFbeta1 and TGFbeta2 play a role in the pathobiology of rhinophyma and
      suggest a means of treatment by neutralizing or down-regulating these cytokines.

PMID- 12055436
TI  - Orthogonal polarization spectral imaging versus intravital fluorescent microscopy
      for microvascular studies in wounds.
AB  - The aim of this study was to validate orthogonal polarization spectral (OPS)
      imaging against intravital fluorescence microscopy (IFM) for microvascular
      measurements in normal skin and during wound healing. Experiments were performed
      on the ears of hairless mice (N = 8). The diameter of arterioles and venules, red
      blood cell velocity in venules, and the functional capillary density were
      assessed under normal conditions using OPS imaging and IFM. After creation of a
      circular wound, these observations were repeated at the identical microvascular
      regions on days 4, 7, 10, and 15. Images were videotaped, and CapImage was used
      for off-line computer-assisted analysis. Using OPS imaging, the microcirculation
      of wounded skin in hairless mice could be observed successfully. The regression
      analyses against standard IFM revealed a significant (p < 0.001) correlation for
      measurements of all microcirculatory parameters investigated (venular diameter:
      r(2) = 0.98, N = 345; red blood cell velocity: r(2) = 0.51, N = 326; functional
      capillary density: r(2) = 0.44, N = 156). However, for diameter as well as for
      functional capillary density measurements, OPS imaging yielded lower absolute
      values compared with IFM. The authors were able to validate OPS imaging against
      IFM for the measurement of microvascular parameters in an animal model of skin
      wound healing. Such a device should now help to study the role of
      microcirculation in physiology and pathophysiology during wound healing in
      patients. First clinical investigations are promising.

PMID- 12055437
TI  - Free flap transfer to the dorsum of the rat: a new technique to avoid
      autocannibalization in free flap studies.
AB  - In this report the authors describe a new method that avoids autocannibalization
      by free transfer of a flap to the dorsum of the rat by means of a simple exposure
      technique. A total of 22 Wistar rats of both sexes (weight, 200-290 g) were used
      in this experiment. An anatomic study performed in 12 rats revealed that a wide
      exposure could be created in the axillary fossa by retracting the inferior tip of
      the scapular bone superiorly (after severing its attachments with the deep
      extrinsic back muscles), the latissimus dorsi muscle laterally, and the serratus
      anterior muscle medially. Furthermore, after obtaining vessel diameter
      measurements, it was ascertained that the subscapular and the lateral thoracic
      vessels could serve as the recipient vessels. Based on the anatomic study, a
      total of 10 conventional groin cutaneous flaps, measuring 2 x 3 cm in size, were
      harvested based on the femoral vessels and transferred to the dorsum of the same
      animal by the exposure method as just described, with microvascular anastomoses
      performed between the femoral vessels of the flap and either the subscapular
      artery and the lateral thoracic vein (N = 5) or the lateral thoracic artery and
      vein (N = 5). Results showed that 9 of the 10 transplanted flaps were totally
      viable on postoperative day 7, giving a success rate of 90%, with one failing
      flap belonging to the latter group. The authors conclude that by this simple
      method of recipient vessel exposure in the axillary fossa, free flap transfer to
      the dorsum of the rat is a simple and reproducible technique by microvascular
      anastomoses performed between the pedicle vessels of a flap and the subscapular
      artery and the lateral thoracic vein. This model offers the unique advantage of a
      dorsally located flap that is protected by autocannibalization. Moreover, daily
      observation and monitoring of the flap are easy and practical without the need to
      have the animal wear protective material such as vest.

PMID- 12055438
TI  - Effects of different vascular patterns and the delay phenomenon on rat ventral
      island flap viability.
AB  - The objective of the current study was to investigate flap viability and to
      determine optimal delay time by designing various blood flow patterns in the
      superficial inferior epigastric (SIE) artery (A) and vein (V) flap model. Flaps
      measuring 7 x 7 cm were created in 42 Sprague-Dawley rats, which were divided
      into six groups. In group I rats (AV-AV), the flap was elevated based on the
      bilateral SIE vessels. In group II rats (AV-A), the flap was elevated based on
      the right SIE vessels and the left artery. In group III rats (V-AV), the flap was
      elevated based on the left-side vein whereas the SIE artery and vein were the
      pedicle on the right side. In group IV rats (V-A), the flap was elevated as a
      venous flap on the left side and was SIE artery based on the right side. In group
      V rats (AV-) the flap was elevated based on the right SIE artery and vein. In
      group VI rats (delay), the SIA artery and vein on the left side were ligated
      without elevation during the first session. The flap was elevated on the right
      SIE artery and vein 7 days after the delay procedure. Percentages of viable flap
      surface area were measured in millimeters with acetate paper on day 5 after
      surgery. The highest viability was seen in group I rats (96.14%), and the delay
      group had the second highest viable area (88.56%). The area that remained viable
      in group II was larger than that of group III (87.41% vs. 72.84%; p < 0.05). The
      least viable areas were observed in group IV. The percentage of viable flap area
      was significantly higher in the delay group when compared with group V rats
      (88.56 +/- 1.06% vs. 60.01 2.58%; p < 0.05). In conclusion, if the contralateral
      pedicle is ligated 7 days before SIE vessel-based island flap elevation, the flap
      can be used safely in a manner that crosses the median. Artery inflow of the flap
      is more important than venous outflow for improvement of flap viability on the
      contralateral side.

PMID- 12055439
TI  - Role of free radicals in necrosis of skin graft compromised with hematoma.
AB  - It has been observed previously that a hematoma affects skin flap survival
      adversely through free radical action. The current study was undertaken to
      determine whether similar mechanisms are operative in skin grafts. The experiment
      was divided into two parts. During part I, 2 x 2 cm2 split-thickness skin grafts
      (STSGs) were harvested from 18 Fischer rats and were divided randomly into three
      groups (each consisted of six grafts), and incubated with plasma, blood, and
      blood plus 70 mg deferoxamine for 48 hours respectively. Tissue samples were
      assayed for lipoperoxidation (malondialdehyde [MDA]), superoxide dismutase (SOD),
      and nitric oxide synthase (NOS). During part II, 36 STSGs were harvested and were
      divided randomly into three groups. The grafts were incubated as in part I for 48
      hours. The STSGs were then affixed to the same dimension recipient beds created
      on the back of 36 inbred rats. Survival was evaluated 7 days postoperatively. The
      results showed that there was no significant difference in MDA and NOS levels
      between each incubated graft group in part I. Only the SOD level in both grafts
      incubated with plasma and blood plus deferoxamine were significantly higher than
      the grafts over blood alone (p < 0.05). During part II, there was no significant
      difference of the average STSG survival percentage between the groups incubated
      with blood and blood plus deferoxamine (35.8 +/- 6.5% and 52.0 +/- 9.5%). The
      survival percentage of the group incubated with plasma was 81.8 +/- 7.3%, which
      was significantly higher than the other two groups (p < 0.01). The authors
      concluded that unlike a distal flap model, the pathological importance of free
      radicals in survival of the STSG over a hematoma is insignificant. A more likely
      hypothesis, as suggested by others, is that a hematoma serves as a barrier
      preventing angiogenesis.

PMID- 12055440
TI  - Extensive cutaneous leishmaniasis of the upper limb in a patient with leukemia.
AB  - An unusual case of extensive cutaneous leishmaniasis of the upper limb in a
      patient with leukemia is presented. A trial of medical therapy (sodium
      stibogluconate) resulted in rapid healing of the large ulcers. The incidence of
      leishmaniasis is increasing globally as a result of the ease of travel and
      migrating populations. Hand surgeons worldwide should have a high index of
      suspicion of this parasitic infection of the upper limb and should be aware of
      its unusual presentation in immunocompromised patients.

PMID- 12055441
TI  - Penile reconstruction for extramammary Paget's disease.
AB  - The authors report their experience of an extremely rare case of extramammary
      Paget's disease presenting a deformational change of the penis, which required
      penile reconstruction after tumor resection. Tumor cells had invaded the dermis
      beyond the basement membrane of the epidermis. Tumor cells were found at the
      epithelium of the urethra, but had not invaded the corpus cavernosum. However,
      fibrotic changes were found in the corpus cavernosum. More than half the length
      of the penis was resected. Penile reconstruction was performed using a free
      sensory radial forearm flap. The defects in the mons pubis, scrotum, and the
      remaining corpus cavernosum were covered using a meshed split skin graft or
      sheeted split skin graft. Ten months after the operation, the tumor had not
      recurred and no metastasis was found. The urinary stream was narrow compared with
      that of a healthy man, but urinary voiding had not been disturbed. Sensory
      recovery was 12 mm with the two-point discrimination test at the distal end of
      the reconstructed penis.

PMID- 12055442
TI  - We must keep moving.

PMID- 12055443
TI  - Finding a window into the skin.

PMID- 12055444
TI  - Electrotherapy reoxygenates inframalleolar ischemic wounds on diabetic patients:
      a case series.
AB  - OBJECTIVE: To retrospectively evaluate the ability of high voltage pulsed current
      (HVPC) to increase microcirculation in critically ischemic wounds (transcutaneous
      oxygen [TcPO(2)] less than 10 mm Hg) and, as a result, to improve wound healing.
      DESIGN AND METHODS: Clinical case series with successive adult diabetic subjects
      (3 men and 3 women) with nonsurgical ischemic malleolar or inframalleolar skin
      lesions, each subject serving as his or her own control. Wound area and TcPO(2)
      were measured periodically. Presence of distal arteriosclerosis was assessed on 5
      patients by 2-dimensional, time-of-flight magnetic resonance angiography. End
      point was either complete wound closure or leg amputation. RESULTS: Maximum mean
      TcPO(2) was 2 +/- 2 mm Hg at the wound edge before the start of electrotherapy.
      After electrotherapy began, maximum TcPO(2) was 33 +/- 18 mm Hg (N=6; P<.05,
      Wilcoxon signed rank test). After treatment with HVPC, 4 patients' wounds healed
      and 2 patients underwent amputation. As expected, healed patients initially
      deteriorated after the start of treatment, but their wounds began healing when
      the perilesion TcPO(2) measurement exceeded 20 mm Hg. Thereafter, the wounds
      closed at a predictable rate. Complete closure occurred for patients who had a
      relatively low atherosclerotic burden. CONCLUSION: The results of this clinical
      case series suggest that electrotherapy can improve periwound microcirculation of
      ischemic inframalleolar skin lesions.

PMID- 12055445
TI  - Incidence and prevalence of pressure ulcers in children.
AB  - OBJECTIVE: To determine the incidence and prevalence of pressure ulcers in
      children. DESIGN: National survey mailed to 234 members of 4 pediatric-specific
      health care databases. PARTICIPANTS: A total of 55 questionnaires were returned
      (25% return rate). Fifty-one of the questionnaires were suitable for obtaining
      prevalence data and 40 were suitable for obtaining incidence data. RESULTS: The
      pressure ulcer incidence rate was 0.29% and the prevalence rate for 1998 was
      0.47%. Many of the contributing factors cited by participants mirrored those seen
      in adult patients with pressure ulcers. CONCLUSION: Under the National Institutes
      of Health guidelines, children can be excluded from pressure ulcer studies that
      include subjects above age 21 because of the rarity of pressure ulcer development
      in the pediatric population. However, separate pediatric pressure ulcer studies
      should be conducted to determine best-practice models for children with pressure
      ulcers.

PMID- 12055446
TI  - How and why to do pressure ulcer risk assessment.
AB  - PURPOSE: To improve clinical practice and the quality of patient care by
      providing a learning opportunity that enhances the participant's understanding of
      pressure ulcer risk assessment. TARGET AUDIENCE: This CME/CE activity is intended
      for physicians and nurses with an interest in learning about pressure ulcer risk
      assessment. OBJECTIVES: 1. Identify the purpose and benefits of using a pressure
      ulcer risk assessment scale. 2. Evaluate pressure ulcer risk by using the Braden
      Scale and its subscales. 3. Identify the interventions that can be implemented
      based on the patient's Braden Scale score.

PMID- 12055447
TI  - Diagnosing necrotizing fasciitis.

PMID- 12055448
TI  - Estimating caloric needs to promote wound healing.

PMID- 12055449
TI  - Medicare documentation guidelines for wound care nurses.

PMID- 12055451
TI  - Conflicts of interest in magnetic resonance imaging: issues in clinical practice
      and research.
AB  - In the use of magnetic resonance imaging (MRI) in medicine and in the conduct of
      MRI research, conflicts of interest are routinely generated. These conflicts are
      not necessarily unique to MRI and are not necessarily considered malpractice or
      misconduct. It is important, however, for clinicians and researchers to
      understand what constitutes a conflict of interest and how to mitigate the
      potential adverse effects of those conflicts on patients and on the integrity of
      research. It also is important for medical professionals to understand the
      changes in the clinical and research environments that make conflicts of interest
      more prevalent and more of a concern to policy makers. Finally, it is important
      for medical professionals who work with MRI to understand some of the
      characteristics of MRI that might increase the prevalence of conflicts of
      interest in clinical practice and research.

PMID- 12055452
TI  - Ethical issues in contrast-enhanced magnetic resonance imaging screening for
      breast cancer.
AB  - Breast magnetic resonance imaging (MRI) screening has been shown to detect early
      breast cancer. The main challenge ahead for breast MRI screening is to prove its
      effectiveness in reducing breast cancer mortality. While this challenge is
      commonly viewed as a scientific, technological, and clinical one, it also carries
      ethical components. This article is concerned with the risks and benefits of MRI
      screening that should be explained to screening participants and discusses the
      evidence needed by policy makers who ultimately will determine a just allocation
      of health care resources to MRI breast cancer screening.

PMID- 12055453
TI  - Ethical issues in imaging nonaccidental injury: child abuse.
AB  - One of the most controversial areas of nonaccidental injury is the medical
      diagnosis of inflicted central nervous system injury and its impact on medical,
      social, and legal outcomes for children and families. This review addresses the
      role of the neuroradiologist in the clinical care of the pediatric patient and as
      an expert medical witness in the area of nonaccidental injury.

PMID- 12055454
TI  - Ethical considerations in image-based screening for coronary artery disease.
AB  - Despite marked advances in the treatment and prevention of coronary artery
      disease (CAD) during the last decade, CAD and its complications continue to
      account for 20% of all deaths in the United States, more than other cause of
      death. Moreover, half of those who die suddenly of an acute myocardial infarction
      have no prior symptoms or overt manifestations of their underlying CAD. As our
      understanding of the pathophysiology of coronary atherosclerosis improves,
      diagnostic tests utilizing magnetic resonance (MR) imaging and gated computed
      tomography are being developed to screen for significant CAD in symptomatic
      individuals and in those who are preclinical or asymptomatic. Patients with known
      or suspected CAD might be candidates for MR studies of myocardial perfusion,
      myocardial contraction under stress, MR coronary arteriography, and plaque
      characterization. One rationale would be to uncover patients before they have a
      silent heart attack to institute preventative therapies. Although clinical
      studies have not definitively demonstrated the efficacy of these modalities,
      screening sites are proliferating and patients are demanding screening tests for
      CAD. Radiologists interpreting these tests should understand their underlying
      rationale, the data referenced to substantiate their use, and their
      responsibility to inform the patient of the results. This review describes
      current concepts of the pathophysiology of CAD, the rationale for the various
      screening tests for CAD that are in use or in development, and the potential
      value of the results of screening to individual patients. The ethical issues
      embodied in the performance of screening tests for CAD are placed in the context
      of the appropriate role of the radiologist as a physician interacting directly
      with a patient.

PMID- 12055455
TI  - Managed care, medical technology, and the well-being of society.
AB  - The growth of managed care could have widespread effects on the structure and
      functioning of the health care delivery system, potentially influencing all
      patients, even those not enrolled in managed care plans. One important mechanism
      by which managed care could have such broad effects is by influencing technology
      development and adoption. This article examines available literature on the
      effects of managed care activity on technology adoption and the implications of
      any effects on patient care, outcomes, and health care costs. Existing literature
      supports the view that managed care has contributed to slowing the adoption of
      new technologies, particularly the high-cost, high-profile technologies that have
      been the focus of the most attention. The literature outlining the effects of
      managed-care-induced changes in technology adoption on patient care and outcomes
      is not large, but what literature there is tends not to find negative effects on
      patient care and outcomes. Specific evidence about costs also is somewhat sparse,
      but it suggests that managed care has contributed to some reduction in health
      care spending, although the extent to which savings will persist over time is
      unclear. Although evidence thus far does not suggest important detrimental
      effects of managed care on care or outcomes and even indicates some benefit
      through savings, it should be noted that existing literature has only explored a
      small number of the many technologies and services that might have been
      influenced, and there remain issues for the future that deserve vigilance.

PMID- 12055456
TI  - CME review: sclerochoroidal calcification: the 2001 Harold Gifford Lecture.
AB  - Sclerochoroidal calcification is a recently recognized ocular condition that is
      characterized by typical geographic yellow-white fundus lesions that usually
      occur bilaterally in adults. It can clinically simulate a number of intraocular
      tumors like choroidal metastasis, choroidal melanoma, and choroidal osteoma.
      Clinical evaluation with ultrasonography, computed tomography, and some
      histopathologic studies have supported the fact the condition represents calcium
      deposition in the sclera and choroid. Early reports suggested that
      sclerochoroidal calcification was usually associated with hypercalcemic
      conditions such as hyperparathyroidism and pseudohypoparathyroidism.
      Subsequently, many patients with sclerochoroidal calcification have had no
      apparent systemic associations and have been classified as idiopathic. However,
      very recent studies have suggested that this ocular condition can also be
      associated with Gitelman syndrome or Bartter syndrome. These are autosomal
      recessive conditions of hypokalemic alkalosis associated with hypomagnesemia and
      deposition of calcium salts in various tissues. Ophthalmologists should be
      familiar with fundus features and systemic associations of sclerochoroidal
      calcification.

PMID- 12055457
TI  - Paradoxical activity of CMV retinitis in patients receiving highly active
      antiretroviral therapy.
AB  - PURPOSE: To report two types of atypical behaviors of cytomegalovirus (CMV)
      retinitis in the highly active antiretroviral therapy (HAART) era, including
      active CMV retinitis in the presence of persistently high CD4 cell counts during
      HAART and CMV retinitis that has not reactivated despite persistently low CD4
      cell counts. METHODS: Prospective, longitudinal, observational study of a cohort
      of 116 patients with acquired immunodeficiency syndrome who had a history of CMV
      retinitis during the HAART era. RESULTS: Sixty (52%) of the 116 patients with
      acquired immunodeficiency syndrome and CMV retinitis were HAART responders.
      Subsequently, HAART failed for 9 of the 60 patients with low CD4 cell counts. Of
      these 9 patients, 5 developed reactivation of CMV retinitis, and 4 remained free
      of CMV retinitis despite CD4 cell counts of <50/microL and lack of anti-CMV
      therapy. Paradoxically, there was a patient with a documented median CD4 cell
      count of 204/microL for 19 months who had newly diagnosed active CMV retinitis.
      CONCLUSION: In the HAART era, CMV retinitis may remain quiescent despite
      extremely low CD4 cell counts, and rarely, CMV retinitis may become active in the
      setting of persistently high CD4 cell counts in a subset of HAART responders.

PMID- 12055458
TI  - Cytomegalovirus retinitis after initiation of highly active antiretroviral
      therapy in HIV infected patients: natural history and clinical predictors.
AB  - PURPOSE: To characterize the natural course and clinical predictors of
      cytomegalovirus (CMV) retinitis in human immunodeficiency virus (HIV)-infected
      patients after initiation of highly active antiretroviral therapy (HAART).
      METHODS: Retrospective analysis of 53 HIV-positive patients (73 eyes with CMV
      retinitis) treated with and without HAART. All participants continued to take
      anti-CMV therapy. Survival analysis was used to characterize the natural course
      of CMV retinitis. Proportional hazards analysis was performed to assess the
      correlation of the nine potential clinical predictors (baseline CD4 count, post
      HAART CD4 count, post-HAART rise in CD4 count, baseline weight, post-HAART rise
      in weight, post-HAART percentage rise in weight, log of baseline HIV viral load,
      log of minimum post-HAART HIV viral load, and post-HAART log unit reduction in
      HIV viral load) with the duration of CMV retinitis remission. RESULTS: Patients
      receiving HAART had a median CMV retinitis remission duration of 574 days (95%
      confidence interval, 336-NA) whereas those not receiving HAART had a median
      remission duration of 80.5 days (95% confidence interval, 28-NA; P < 0.001).
      Within the HAART-treated population, the minimal viral load reached after HAART
      was the only clinical predictor to demonstrate significance (P = 0.0075). Several
      other clinical predictors demonstrated borderline significance; however, this was
      most likely due to the high correlation of these variables with the minimum post
      HAART viral load. A potential secondary clinical predictor identified was the
      post-HAART rise in CD4 count (P = 0.085). CONCLUSION: With the introduction of
      HAART, HIV-infected patients have much longer remission durations from recurrent
      CMV retinitis. The minimum HIV viral load level reached after the initiation of
      HAART treatment appears to be more important than other clinical variables in the
      prediction of favorable CMV retinitis remission status. Furthermore, a rise in
      CD4 T-lymphocyte count by itself appears to be a less significant clinical
      predictor but may be useful in combination with the HIV viral load data.
      Selective discontinuation of anti-CMV therapy may be considered in patients with
      a favorable set of clinical predictors.

PMID- 12055459
TI  - Prevalence of visual symptoms among patients with newly diagnosed cytomegalovirus
      retinitis.
AB  - PURPOSE: To determine the prevalence and type of visual symptoms among human
      immunodeficiency virus (HIV)-positive patients with newly diagnosed
      cytomegalovirus (CMV) retinitis. METHODS: The authors conducted a retrospective
      review of the charts of all HIV type 1-infected patients at Parkland Memorial
      Hospital (Dallas, TX) who had newly diagnosed CMV retinitis between July 1, 1993,
      and September 30, 1997. Information recorded included demographics, results of
      laboratory evaluations including CD4 cell count, visual symptoms at the time of
      diagnosis, and the zone and extent of retinal involvement at presentation. Visual
      symptoms in the patients with CMV retinitis were compared with those in a control
      group of HIV-positive patients who were screened for CMV retinitis but were not
      diagnosed with retinitis. RESULTS: Of 183 eyes (138 patients), 83% (88% of
      patients) had visual symptoms at the time of diagnosis. The most common
      presenting symptoms were blurred vision (67% of patients), floaters (49%),
      flashes of light (16%), eye pain (7%), and scotomata (3%). Compared with the
      control group of patients without CMV retinitis, patients with CMV retinitis were
      more likely to have any eye symptoms (88% versus 53%, respectively) as well as
      blurred vision, floaters, and either blurred vision or floaters (P < 0.0001).
      Eyes with zone 1 retinal involvement had an 88% incidence of visual symptoms at
      the time of diagnosis compared with 77% of eyes with peripheral retinal
      involvement (zones 2 and 3) (P > 0.05). Patients with zone 1 disease were more
      likely to note blurred or decreased vision than were patients with zone 2 or 3
      disease (75% versus 47%, respectively; P < 0.0001). Eyes with <25% retinal
      involvement had a 76% rate of visual symptoms, which was significantly lower than
      the 90% rate noted among eyes with >25% retinal involvement (P < 0.05).
      CONCLUSIONS: Most HIV-infected patients with newly diagnosed CMV retinitis had
      visual symptoms at presentation regardless of the zone of retinal involvement.
      The incidence of visual symptoms correlated with the degree of retinal
      involvement.

PMID- 12055460
TI  - Retinal detachment in patients with a preexisting glaucoma drainage device:
      anatomic, visual acuity, and intraocular pressure outcomes.
AB  - PURPOSE: To report anatomic, visual acuity, and intraocular pressure (IOP)
      outcomes after retinal detachment (RD) repair in patients with a preexisting
      glaucoma drainage device. METHODS: Consecutive case series including patients
      with a preexisting glaucoma drainage device who underwent RD repair at Bascom
      Palmer Eye Institute between 1989 and 1999. RESULTS: Ten patients were identified
      with a mean follow-up of 18 months. Initial RD repair included pars plana
      vitrectomy (PPV) and fluid-gas exchange in four patients, scleral buckling
      procedure (SBP) in two, PPV and SBP in three, and pneumatic retinopexy in one.
      Three patients initially treated with SBP or pneumatic retinopexy developed
      recurrent RD secondary to proliferative vitreoretinopathy. All patients
      eventually underwent PPV. At 6 months, the retina was attached in eight patients,
      and nine patients had an IOP no greater than 21 mmHg. Although postoperative
      vision was stable or improved compared to preoperative levels in seven patients,
      visual acuity at 6 months was worse than 2/200 in only four patients, largely
      because of preexisting advanced glaucoma. CONCLUSIONS: In eyes with RD and a
      preexisting glaucoma drainage device, PPV with fluid-gas exchange was the most
      successful approach in achieving retinal reattachment. Although anatomic success
      is usually achieved and IOP is usually controlled, visual acuity outcomes are
      often poor, largely because of preexisting advanced glaucoma.

PMID- 12055461
TI  - Scleral buckling technique without retinopexy for treatment of rhegmatogeneous: a
      pilot study.
AB  - PURPOSE: To evaluate the role of retinopexy in the surgical management of primary
      rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy.
      The primary outcome was retinal attachment, and secondary outcomes were visual
      acuity results and complications. METHODS: A randomized controlled trial
      including 60 patients with RD caused by a break or a group of breaks no larger
      than one clock hour. Thirty eyes received no retinopexy (group 1), and 30 eyes
      received transscleral cryotherapy (group 2). An encircling buckle was placed in
      all eyes. In eyes with posterior breaks, segmental buckles were also added. In
      some eyes, subretinal fluid drainage or anterior chamber paracentesis and/or
      intravitreal air bubble injection was performed. RESULTS: No differences were
      found between the groups in terms of the preoperative clinical variables
      evaluated: age; sex; axial length; lens status; type, number, and location of
      breaks; extension of detachment; and macula status. There were no differences in
      the surgical procedures performed. The reattachment rate in group 1 was 90%, and
      in group 2, it was 87% (a difference that was not significant [P = 1.00]). Final
      visual acuity improved by two lines or more in 22 patients in group 1 and in 20
      patients in group 2 (P = 0.317). CONCLUSIONS: Our results indicate that primary
      rhegmatogenous RD can be successfully treated with scleral buckling without
      retinopexy.

PMID- 12055462
TI  - Epidemiology survey of rhegmatogenous retinal detachment in Beixinjing District,
      Shanghai, China.
AB  - PURPOSE: To investigate the recent incidence and related risk factors of
      rhegmatogenous retinal detachment (RRD) in Chinese people. METHODS: This study
      was an incidence survey based on data for 108,132 persons in Beixinjing District,
      Shanghai, China. Patients with RRD were inpatients, outpatients, and patients
      from the local health network. Patients with RRD were compared with control
      subjects who were matched by sex, age, and block of residence. Previous
      population data were used to estimate the whole and specific incidence of RRD.
      Some factors relevant to the incidence of RRD were found by comparing the
      patients with RRD with the control subjects. RESULTS: Between January 1996 and
      December 1999, 61 cases of RRD occurred. The annual incidence of RRD was 11.3
      cases per 100,000 population in 1996, 14.1 cases per 100,000 population in 1997,
      14.1 cases per 100,000 population in 1998, and 17.9 cases per 100,000 population
      in 1999. The average annual incidence was 14.4 cases per 100,000 population (95%
      confidence interval, 10.0-18.6). There were 29 males and 32 females with RRD. The
      incidence of RRD among persons older than 40 years was high, especially among
      those between 40 and 59 years of age. The proportion of individuals with high
      myopia (more than -6 diopters) was significantly higher in the patient group than
      in the control group (P < 0.001). CONCLUSION: The annual incidence of RRD among a
      local Chinese population increased over 4 years. This disease is strongly
      associated with high myopia and age.

PMID- 12055463
TI  - Grading of infrared confocal scanning laser tomography and video displays of
      digitized color slides in exudative age-related macular degeneration.
AB  - PURPOSE: To detect and localize exudative lesions in exudative age-related
      macular degeneration and to compare images obtained from infrared scanning laser
      tomography and video displays of digitized color slides in detection and
      localization of exudation. METHODS: In a prospective study, 11 eyes of 11
      patients with exudative age-related macular degeneration were studied. From 32
      images with infrared scanning laser tomography, confocal images were chosen in
      the following focal planes: anterior to the retina, the retinal surface, and the
      deep retina. Using the fluorescein angiogram as a standard, three retinal
      specialists rank-ordered the ability to discern the lesion in these confocal
      images, the summary of confocal images, and video displays of digitized color
      slides that were adjusted to the same resolution as that of the confocal images
      (approximately 23 microm per pixel). RESULTS: For choroidal neovascularization,
      both the retinal surface image and the summary image were rated superior to video
      displays of digitized color slides (P < 0.004). The confocal images were ranked
      in the following fashion: best, retinal surface; next, deep retina; and then,
      anterior to the retina (P < 0.01). For pigment epithelial detachment, all three
      confocal images and summary images were superior to video displays of digitized
      color slides (P < 0.002). There were no significant differences among the
      confocal images (P = 0.95). CONCLUSION: Infrared confocal imaging was superior to
      video displays of digitized color slides for visualization of both pigment
      epithelial detachment and choroidal neovascularization. This technique could have
      an impact on epidemiologic studies.

PMID- 12055464
TI  - The ultra-late phase of indocyanine green angiography for healthy subjects and
      patients with age-related macular degeneration.
AB  - PURPOSE: To compare the characteristics of residual fundus fluorescence observed
      in the ultra-late phase of indocyanine green (ICG) angiography, in normal
      subjects and in patients with age-related macular degeneration (ARMD). METHODS:
      ICG angiography was performed on 38 patients, 21 had ARMD, 9 were normal subjects
      aged >62, and 8 were normal subjects aged <36. The intensity and pattern of
      fluorescence from angiograms obtained in the ultra-late phase, 24 hours after dye
      injection, was also recorded and analyzed. RESULTS: In the ultra-late phase, 95%
      of ARMD eyes with CNV showed geographic hypofluorescent lesions. All of the CNV
      that could be delineated with fluorescein and/or ICG angiography were located in
      these geographic lesions. In 73% of ARMD eyes without CNV, these hypofluorescent
      lesions occurred, while age-matched normal subjects had no hypofluorescent
      lesions. The mean intensity of fluorescence in the normal older subject group was
      significantly higher than that seen in the normal young subject group.
      CONCLUSIONS: Increased fluorescence, associated with older subjects, in the ultra
      late phase of ICG angiography may reflect aging changes in the chorioretinal
      complex. Geographic hypofluorescent areas, demonstrated only in the ultra-late
      phase, associate with ARMD and may represent areas predisposed to CNV
      development.

PMID- 12055465
TI  - Multiple evanescent white dot syndrome in patients with multifocal choroiditis.
AB  - BACKGROUND: Controversy exists as to whether a common causal entity is
      responsible for multifocal choroiditis (MFC) and multiple evanescent white dot
      syndrome (MEWDS). It is commonly known that patients with MEWDS can later develop
      manifestations of MFC, but the reverse is rarely seen. PURPOSE: To report cases
      of MEWDS in patients previously diagnosed with MFC. DESIGN: Retrospective case
      series. PARTICIPANTS: Four female patients 29 to 34 years old. METHODS: The
      charts of four patients with acute unilateral onset of MEWDS and evidence of
      previous MFC were examined retrospectively. MAIN OUTCOME MEASURES: Photographic
      and angiographic interpretation of fundus appearance. RESULTS: At the time of
      diagnosis with typical MEWDS, one patient had a documented previous episode of
      acute MFC; one patient had previous bilateral choroidal neovascularization
      associated with discrete, posterior atrophic scars; and two patients had
      peripheral discrete chorioretinal pigmented lesions and peripapillary atrophy.
      CONCLUSIONS: MEWDS may occur after MFC. Now that both directions of disease
      progression, MFC to MEWDS and MEWDS to MFC, have been well documented, it is
      likely that there is a common host susceptibility between these two distinct
      clinical diseases, if not a common pathogenesis.

PMID- 12055466
TI  - Visual and anatomical outcome following submacular surgery for choroidal
      neovascularization secondary to Candida endophthalmitis.
AB  - PURPOSE: To report the long-term visual and anatomical outcomes for patients
      treated with submacular surgery for choroidal neovascularization associated with
      endogenous candidal endophthalmitis. METHODS: Review of the medical records,
      fluorescein angiograms, fundus photographs, and histopathologic specimens of
      patients treated with submacular surgery for choroidal neovascularization
      following candidal endophthalmitis. RESULTS: This series included 3 patients (1
      woman and 2 men) who were 26, 30, and 60 years of age. Each patient had received
      systemic antifungal treatment for culture-proven candidal septicemia before the
      development of choroidal neovascularization. Each patient had bilateral choroidal
      neovascularization diagnosed by biomicroscopic examination and angiographic
      appearance: 2 eyes had an active subfoveal membrane; 2, an active juxtafoveal
      subretinal membrane; and 2, a mixture of active subfoveal neovascularization with
      subfoveal fibrosis. Submacular surgery was performed on five eyes with choroidal
      neovascularization; one eye with subfoveal fibrosis was observed. Visual acuity
      improved substantially in 4 eyes of 3 patients treated with submacular surgery.
      Visual improvement was limited in the two eyes with preexisting submacular
      fibrosis. During 13-month to 82-month follow-ups, vision remained stable, with no
      recurrence of neovascularization. CONCLUSION: Choroidal neovascularization can
      cause severe visual loss in patients with endogenous candidal infection.
      Submacular surgery with removal of choroidal neovascularization may restore
      vision in selected patients. Subfoveal fibrosis may limit visual improvement.

PMID- 12055467
TI  - Aqueous humor nitric oxide levels in patients with Behcet disease.
AB  - PURPOSE: The purpose of this study was to quantify aqueous humor nitric oxide
      levels in patients with Behcet uveitis and age-matched controls to assess how
      nitric oxide is involved in this ocular condition. METHODS: Samples of aqueous
      humor were collected from 11 patients with Behcet uveitis who were undergoing
      cataract surgery. Sampling was done by paracentesis at the beginning of the
      operation. Similar samples were collected from 20 age-matched normal patients
      (controls). For each sample, we used the spectrophotometric method based on the
      Griess reaction to determine the amount of nitrite, which is the stable
      metabolite of nitric oxide. RESULTS: The amount of nitrite in aqueous humor
      samples from patients with Behcet disease was above the detection limit in 8 of
      11 cases; the mean level +/- SEM was 2.13 +/- 0.621 micromol/L. Levels in the
      control group were below the detection limit in all cases (<0.08 micromol/L).
      There was a statistically significant difference between the aqueous humor
      nitrite levels in patients with Behcet disease and those in controls (P =
      0.00002). CONCLUSIONS: Aqueous humor nitric oxide levels are elevated in patients
      with a history of Behcet disease.

PMID- 12055468
TI  - Flickering light increases retinal blood flow.
AB  - PURPOSE: To examine the retinal blood flow in normal eyes before and during
      retinal stimulation by flickering light. DESIGN: A prospective cross-sectional
      study. PARTICIPANTS AND TESTING: Twenty-seven eyes of 27 normal subjects with a
      mean age +/- SD of 38 +/- 15 years (study I) and 21 eyes of 21 normal subjects
      with a mean age +/- SD of 46 +/- 17 years (study II) were examined with respect
      to capillary retinal blood flow and central retinal artery and central retinal
      vein blood flow velocities during flickering light stimulation. A luminance
      flicker light with a frequency of 8 Hz increased the neuronal activity of retinal
      ganglion cells. In study I, the retinal capillary blood flow was measured before
      and during flickering by scanning laser Doppler flowmetry (670 nm, Heidelberg
      Retina Flowmeter). In study II, the blood flow velocities in the central retinal
      artery and central retinal vein were examined by pulsed Doppler sonography. MAIN
      OUTCOME MEASURES: Change in blood flow velocities in the central retinal artery
      and vein and in retinal capillary blood flow after full-field flicker
      stimulation. RESULTS: In study I, measurements of blood flow during retinal
      flicker stimulation showed a significant increase in the mean value of blood flow
      +/- SD from 317 +/- 72 arbitrary units to 416 +/- 103 arbitrary units. The change
      was on average 46 +/- 19%. In study II, the systolic and end-diastolic blood flow
      velocities in the central retinal artery increased significantly (P < 0.0001):
      systolic, 9 cm/s to 15 cm/s (+62%); end-diastolic, 2.7 cm/s to 5.3 cm/s (+96%).
      In the central retinal vein, the systolic and end-diastolic blood flow velocities
      increased significantly (P < 0.0001): systolic, 4.3 cm/s to 6.7 cm/s (+56%); end
      diastolic, 1.8 cm/s to 3.6 cm/s (+100%). The authors found no significant change
      in blood pressure and heartbeat frequency. CONCLUSIONS: Visual stimulation of the
      retina by flickering light strongly increased the juxtapapillary retinal
      capillary blood flow and central retinal artery blood flow velocity in normal
      eyes.

PMID- 12055469
TI  - Diagnostic and therapeutic challenges.

PMID- 12055470
TI  - A retinal tear associated with multiple evansecent white dot syndrome.

PMID- 12055471
TI  - Oral valacyclovir in the treatment of acute retinal necrosis syndrome.

PMID- 12055472
TI  - Two Japanese patients with mutations in the XLRS1 gene.

PMID- 12055473
TI  - Choroidal osteoma in a patient with contralateral persistent hyperplastic primary
      vitreous.

PMID- 12055474
TI  - Crystalline retinopathy associated with retinal dialysis and chronic retinal
      detachment.

PMID- 12055475
TI  - Retinochoroidal anastomoses and a choroidal neovascular membrane in a macular
      exudate following treatment for retinal macroaneurysms.

PMID- 12055476
TI  - Topographical analysis of the visual field in tilted disk syndrome.

PMID- 12055477
TI  - An unusual case of Sturge-Weber syndrome in association with phakomatosis
      pigmentovascularis and Klippel-Trenaunay-Weber syndrome.

PMID- 12055478
TI  - Retinal neovascularization in choroidal melanoma without retinal ischemia.

PMID- 12055479
TI  - Radial optic neurotomy for central retinal vein obstruction.

PMID- 12055480
TI  - Radial optic neurotomy for central retinal vein obstruction.

PMID- 12055481
TI  - Retinal and choroidal microvascular embolization with methylprednisolone.

PMID- 12055482
TI  - Raising the bar during a nursing shortage.

PMID- 12055483
TI  - Tough times in healthcare: solving the problem "upstream".

PMID- 12055484
TI  - Creating a great place to work: strategies for retaining top talent.

PMID- 12055486
TI  - Managing the insubordinate nurse.

PMID- 12055485
TI  - Satisfying nurses on job factors they care about: a Taiwanese perspective.

PMID- 12055487
TI  - Nurse staffing and healthcare-associated infections: proceedings from a working
      group meeting.
AB  - The nation is facing a nursing shortage that is creating a crisis for quality
      healthcare and patient safety. Research has documented that problems with nurse
      staffing are associated with healthcare-associated infections and other adverse
      events that affect patient outcomes. These ominous facts, stated during the
      opening of an expert consultants meeting convened by the Division of Healthcare
      Quality Promotion, Centers for Disease Control and Prevention, laid the
      foundation for a day-long discussion and a call to action to address a growing
      crisis in healthcare. The authors summarize the proceedings of this meeting and
      present the consultants' suggestions for drawing national attention to this
      issue.

PMID- 12055488
TI  - Realizing your marketing influence, Part 2: marketing from the inside out.
AB  - Do your key stakeholders (staff, physicians, and patients) consider your
      organization to be exceptional? Has your organization invested the resources
      necessary to support staff and physicians in delivering the high level of care
      they strive to give? An organization's managers who can enthusiastically answer
      "yes" to these questions are in a good position to promote its healthcare system
      aggressively. Managers who cannot answer affirmatively, in good conscience, must
      invest in creating a healthy environment for staff that is rich with the
      resources that will enable all employees to deliver optimal care and service.
      Until this is achieved, no amount of promotion will be enough to move a
      healthcare system to a market leadership position. This is the second in a series
      of three articles that moves readers from broad marketing strategy to specific
      applications. The first article laid the foundation for developing a market
      driven strategic plan; the third will focus on using professional certification
      as a marketing tool.

PMID- 12055489
TI  - Key ethical issues encountered in healthcare organizations: perceptions of nurse
      executives.
AB  - By the very nature of their daily work, nurse executives find themselves at the
      crossroads of the changing and challenging healthcare ethical environment in
      which clinical ethics and organizational ethics often collide. The authors
      present the findings of a survey of members of American Organization of Nurse
      Executives aimed at more clearly identifying the key ethical issues encountered
      in healthcare organizations by their nurse executives and others. Implications of
      the findings for healthcare organizations and their managers also are discussed
      briefly.

PMID- 12055490
TI  - Developing indicators of nursing quality to evaluate nurse staffing ratios.
AB  - Concerns about the adequacy of patient care and safety in the state of California
      led to legislation that required the implementation of mandatory nurse staffing
      ratios. The authors describe a novel approach for identifying indicators that
      could be used to evaluate the impact of these regulations on quality of care and
      patient outcomes. The results of this project demonstrate that this is a useful
      method for identifying indicators appropriate for use in outcomes research with a
      focus on structural predictors of quality in healthcare.

PMID- 12055491
TI  - Ethics and computer-mediated communication: implications for practice and policy.
AB  - Computer-mediated communication, or email, has become a common workplace
      practice. Interviews with Army nurse managers (n = 9) and their staff nurses (n =
      13) revealed that nurses incorporate the ethical principles of autonomy,
      beneficence, nonmaleficence, and justice into their computer-mediated
      communication use, but to varying degrees. Without clearly defined policies to
      guide computer-mediated communication practices, informal norms evolve that have
      an impact on both individual and corporate communication. The authors provide
      insight into the ethical considerations that have an impact on computer-mediated
      communication use. The spectrum of participant interpretation of appropriate use
      of this type of communication suggests the need for policies to establish clear
      boundaries for workplace usage. Policy recommendations are included.

PMID- 12055493
TI  - Measurement and health locus of control among children.

PMID- 12055492
TI  - Nursing exploration summer camp: improving the image of nursing.
AB  - Improving the image of nursing and finding ways to encourage young people to
      enter the nursing field are two areas that need attention from nurse executives.
      That concept was turned into reality with Inova Nursing Exploration Summer Camp
      2001, a camp for seventh and eighth graders who are exploring their interest in
      nursing careers. The camp was a unique partnership among a county public school
      system, a local university, and an integrated healthcare system. The program,
      developed by the system nurses in consultation with middle school educators,
      introduced students to the nursing profession via demonstrations, site visits at
      multiple hospitals, role-playing, discussions, and a trip to the local nursing
      school to experience life as a nursing student. The authors discuss the planning,
      implementation, and outcome of this unique summer camp.

PMID- 12055495
TI  - Children's psychological responses after critical illness and exposure to
      invasive technology.
AB  - Children hospitalized in pediatric intensive care units (PICUs) are subjected to
      highly invasive interventions necessary in overcoming the critical period of
      their illness, yet little is known about their subsequent psychological
      adjustment. The purposes of this study were to compare the psychological
      responses of children hospitalized in a PICU with those of children hospitalized
      on a general ward and to identify clinically relevant factors that might be
      associated with psychological outcome. A prospective cohort design was used to
      follow 120 children for 6 months after PICU and ward discharge. Groups were
      compared on the children's sense of control over their health, their medical
      fears, posttraumatic stress, and changes in behavior. Relationships between
      children's responses and their age, the invasive procedures to which they were
      exposed, severity of illness, and length of hospital stay were also examined. No
      significant group differences were found. However, children who were younger,
      more severely ill, and who endured more invasive procedures had significantly
      more medical fears, a lower sense of control over their health, and ongoing
      posttraumatic stress responses for 6 months postdischarge. Findings indicate that
      regardless of the hospital setting, invasiveness coupled with length of stay and
      severity of illness in young children may have adverse long-term effects.

PMID- 12055494
TI  - Home environmental influences on children's television watching from early to
      middle childhood.
AB  - Identifying correlates of children's television (TV) watching could help identify
      strategies to reduce children's TV watching and impact children's weight status.
      Children's TV time and home environment factors were assessed longitudinally
      among 169 families with children followed from 6 to 12 years of age. TV watching
      increased with age, as did the number of in-home TVs and the presence of
      videocassette recorders (VCRs), the frequency of meal eating while watching TV,
      and the percentage of children with bedroom TVs. Greater meal eating while
      watching TV was consistently related to overall TV watching and increases in TV
      watching over time. The number of in-home TVs and the presence of a bedroom TV
      were less consistent correlates. TV watching was related to weight status when
      children were younger, and when children were older, more than 2 hours of TV
      daily was a risk factor for higher weight. Modifying TV access, particularly by
      reducing the frequency of meals eaten while watching TV, could promote lower
      children's TV watching and adiposity.

PMID- 12055496
TI  - The Brigance Infant and Toddler Screen: standardization and validation.
AB  - The goal of this study is to present research behind the downward extension of
      the Brigance Screens into the 0- to 2-year-old age range. Items were selected
      from the Brigance Inventory of Early Development (standardized on 1156 children)
      to produce fine motor, receptive language, expressive language, gross motor, self
      help, and social-emotional subtests. Sites included 29 pediatric offices, day
      care centers, and developmental evaluation centers in 22 states. Subjects were
      408 children, 0 to 24 months of age. Internal consistency, test-retest, and
      interrater reliability ranged from 0.98 to 0.99 for both the Infant and Toddler
      Screens. Parent report and direct elicitation versions/observation varied by an
      average of only one point. Correlations with diagnostic measures were high (0.46
      to 0.91). Specificity ranged from 85% to 86% and sensitivity ranged from 76% to
      77%. Accordingly, the Brigance Infant and Toddler Screens are shown to be
      accurate, valid, and reliable tools that can be administered by a range of
      professionals using either parent interview or direct elicitation/observation or
      both.

PMID- 12055497
TI  - Cosleeping in young Korean children.
AB  - This study was an attempt to evaluate the present profile of parent-child
      cosleeping, to investigate the characteristics of those children who cosleep with
      their parents, and to determine the factors influencing cosleeping in Korea.
      Observed subjects consisted of 427 young Korean children aged 12 to 84 months. We
      used an interview method. The incidence of cosleeping was 377 (88.2%). Cosleeping
      decreased with increasing age. Cosleeping in Korean society was affected mostly
      by the age of parents and children, attitudes of the mother to cosleeping, and
      Korean traditional cultural values. The practice of cosleeping in young Korean
      children is very common and socially acceptable to Korean parents as a natural
      part of the child-rearing process. Korean family values and a cultural value
      system emphasizing familial bonds and interpersonal interdependence seems to act
      as positive reinforcing factors for the practice of cosleeping.

PMID- 12055498
TI  - Measurement methodology in children's health locus of control.
AB  - Health locus of control scales for children are often constructed in an
      agree/disagree format. It was hypothesized that the structure of the instrument
      may be in part responsible for the finding that young children (7-8 yr) have an
      external health locus of control relevant to children several years older. The
      original version and a revised version, using a choice of attribution format,
      were both administered to 444 students (98% of eligible students) attending 10
      second-grade classes. Although the mean scores for the two formats were the same,
      32.0 (SD = 3.3), item level analyses showed poor agreement (kappa, -.005-.41) and
      significant bias in disagreements on 15 of the 20 items. Changes in the wording
      of the questions led to different results, indicating possible limitations in
      either format. The observation that young children likely have a mixed health
      locus of control indicates that health educators may benefit from employing both
      internal and external sources of reinforcement to promote healthy behaviors in
      young children.

PMID- 12055500
TI  - Quantity counts: amount of child care and children's socioemotional development.

PMID- 12055501
TI  - A difficult adjustment to school: the importance of family constellation.

PMID- 12055502
TI  - Reflections on interdisciplinary collaboration in the new millennium:
      perspectives and challenges.

PMID- 12055509
TI  - What's new in trauma in the past 10 years.

PMID- 12055510
TI  - Low-pressure resuscitation from hemorrhagic shock.

PMID- 12055511
TI  - Perioperative head injury management in the multiply injured trauma patient.

PMID- 12055512
TI  - Sedation and anesthesia for diagnostic and therapeutic procedures in acute trauma
      patients outside the operating room.

PMID- 12055513
TI  - Perioperative considerations in pediatric traumatic brain injury.

PMID- 12055514
TI  - Airway pressure release ventilation in the acute respiratory distress syndrome
      following traumatic injury.

PMID- 12055515
TI  - Anesthetic management of spinal cord injury: clinical practice and future
      initiatives.

PMID- 12055522
TI  - The compounding pharmacist: a home care and hospice partner.
AB  - Home care and hospice nurses see difficult medical problems requiring
      individualized treatment and medication strategies. This article provides the
      basics of how a specialized type of pharmacy practice--the compounding pharmacy-
      can become invaluable to your care team.

PMID- 12055523
TI  - Lessons learned from telehealth pioneers.
AB  - Just as American pioneers imagined a future in the West, telehealth visionaries
      envisioned a new way of delivering healthcare. Four home care telehealth
      innovators share their experiences including the support and barriers associated
      with this new technology. Each of the users interviewed in this article were
      pioneers in using the LifeSigns telehealth monitor, which consists of a monitor
      that measures a patient's blood pressure, pulse, ECG, and oxygen saturation in
      the home. Each user adopted the technology in various ways that would meet their
      specific needs, making their experiences both similar and unique. Their responses
      will assist home care organizations, clinicians, and clinical managers in
      recognizing how telehealth can be efficiently implemented in their settings.
      Survey participants were Baptist Home Care (BHC), New Brunswick Heart Center in
      Canada (NBHC), University of Tennessee Medical Center (UTMC), and Cardiovascular
      Home Care (CHC), Fort Worth, TX.

PMID- 12055524
TI  - Dealing with drainage: the what, why, and how of wound exudate.
AB  - Managing exudate is a critical factor in reaching successful outcomes. Accurately
      assessing the quantity and quality of exudate is essential to a comprehensive
      assessment and the development of an initial plan of care. Likewise, skilled care
      is required to accurately determine healing progression and modifications to the
      care plan. This article provides the scientific rationale and tips for practice
      to update clinicians on this important competency.

PMID- 12055525
TI  - The heat is on: protecting your patients from nature's silent killer.
AB  - Hot weather may be uncomfortable, but for many, it can be a killer. This article
      describes different types of heat-related illness, risk factors for heat stroke,
      and outlines targeted nursing interventions and critical environmental
      assessments. Nurses can use this information to identify at-risk patients and
      conduct patient and family teaching. Because home care and hospice nurses and
      other staff often work in severe heat, this knowledge is also important for
      personal health and safety.

PMID- 12055526
TI  - Pain management of chronic nonmalignant neuropathic pain.
AB  - Chronic nonmalignant neuropathic pain is difficult to manage. A challenging case
      dealing with chronic neuropathic pain subsequent to thoracotomy syndrome and
      reflex sympathetic dystrophy syndrome is presented. Strategies and approaches to
      aggressively manage this type of pain are presented.

PMID- 12055527
TI  - Speech-language pathologists add value to home care.
AB  - Speech-language pathologists play an important role in the management of home
      care patients. This article describes the types of patients typically seen, the
      treatments rendered, and how the home care nurse can refer and work with these
      important team members.

PMID- 12055528
TI  - Documentation of wound exudate amount leads to dressing reimbursement after
      discharge.

PMID- 12055529
TI  - Can you pass HHN's HIPAA quiz?

PMID- 12055530
TI  - Phlebotomy tools of the trade: part 2: surveying the antecubital area.

PMID- 12055531
TI  - Home health: a nurse's responsibility does not end upon recommending a patient go
      to the hospital.

PMID- 12055534
TI  - [Scarification in Burkina-Faso. Signification, practices and future].

PMID- 12055535
TI  - [Hospitalization criteria for erysipelas: prospective study in 145 cases].
AB  - INTRODUCTION: Two recent studies conducted in France among general practitioners
      have shown that they only hospitalized between 20 to 50 percent of patients with
      erysipelas seen in private practice. We therefore conducted a hospital-based,
      prospective study designed to determine the hospitalization criteria for
      erysipelas, since a number of patients are also hospitalized directly through the
      emergency department. PATIENTS AND METHODS: This prospective, hospital-based
      study, included patients hospitalized for clinical diagnosis of erysipelas in 9
      centres in north-eastern France. Clinical data were recorded using a standard
      questionnaire filled-in during the first 72 hours of hospitalization. They
      included: demographic (name and first name initials, age, sex) and clinical
      (location of erysipelas) characteristics, as well as the origin of the patient
      (home, emergency department, other department), the reasons for hospitalization
      (severity of local or systemic signs, suspicion of deep vein thrombosis, location
      on the face, age over 60 years, associated diseases, absence of improvement after
      ambulatory treatment, socioeconomic reasons or on principle hospitalization).
      Patients hospitalized by (or without) a general practitioner were compared using
      Chi-2 and Student t tests. RESULTS: One hundred forty-five adults (80 women and
      65 men; mean age 61 +/- 20 years) were included in the study: 89 patients (61 p.
      100) were hospitalized by a general practitioner whereas 56 (39 percent) went
      directly to the emergency department. In 128/145 cases (88 p. 100), erysipelas
      was localized on the lower limbs. The mean number of reasons for hospitalization
      per patient was of 2.2 +/- 1.2. The most frequent reason for hospitalization was
      an associated disease (diabetes, obesity, alcoholism, immunodeficiency), present
      in 77 cases (53 p. 100). Patients hospitalized through a general practitioner
      were older than those hospitalized directly through the emergency department (68
      vs 51 years; p<0.001). Patients hospitalized by a general practitioner more
      frequently had an erysipelas located on the lower limbs (94 p. 100 vs 79 p. 100;
      p<0.001) and the mean number of reasons for hospitalization was greater (2.4 vs
      1.7; p<0.001), especially suspicion of deep vein thrombosis and elevated mean
      age. The treatment started during hospitalization was intravenous penicillin G in
      67 cases (46 p. 100), oral pristinamycin in 28 cases (19 p. 100) and intravenous
      or oral amoxicillin in 9 cases (6 p. 100). COMMENTS: This study demonstrates the
      existence of two distinct courses of hospitalization for erysipelas. Patients
      hospitalized by a general practitioner were older and their erysipelas more
      frequently located on the lower limbs and deep vein thrombosis was suspected. Our
      study also shows the emergence of a population of patients younger and without
      medical supervision, for whom the general practitioner is replaced by the
      emergency department of the local hospital. Nevertheless, the most frequent
      reason for hospitalization in both groups is the existence of an associated
      disease, possibly responsible for further complications.

PMID- 12055537
TI  - [Sunscreens: use in pregnant women at Casablanca].
AB  - BACKGROUND: Photoprotection with sunscreens is recommended in hyperpigmentation,
      particularly in pregnancy-related form. The aim of this study was to evaluate the
      use of sunscreens in pregnant women and to determine whether melasma was
      correlated to sunscreen use. PATIENTS AND METHODS: Four hundred and fifteen
      pregnant women were surveyed by a standardized questionnaire on the presence of
      melasma and their use of sunscreens. The study took place in Casablanca, Morocco,
      in two public maternity hospitals and two private gynaecologic centres, from
      April 1999 to July 1999, during antenatal consultations. RESULTS: The mean age of
      the 415 pregnant women was 29 +/- 6 years. One hundred and fifty-one women (37 p.
      100) had a melasma and 72 (17 p. 100) used a sunscreen at their inclusion in the
      study. Women with melasma used sunscreens in 18.8 p. 100 and the others in 16.6
      p. 100. Users of sunscreens differed from non-users in their higher level of
      instruction, professional activity, presentation in private practice and of urban
      origin. DISCUSSION: This study showed a low incidence of sunscreen use in our
      population of pregnant women. Melasma wasn't a reason for using sunscreens.
      However, access to medical information, especially to photoprotection advice, and
      the financial possibility of buying the product led to larger use of sunscreens.
      Up to now no study has confirmed that sunscreens can prevent melasma in dark
      phototype women with pregnancy. It would therefore be difficult to recommend them
      to pregnant women.

PMID- 12055536
TI  - [Nutritional status assessment of patients with leg ulcers].
AB  - INTRODUCTION: Nutritional deficiencies may delay the wound healing process. The
      aim of this study was to evaluate the prevalence of protein malnutrition in
      patients presenting with a leg ulcers and to determine which clinical data can
      predict malnutrition on population. PATIENTS AND METHODS: This prospective survey
      included community patients, hospitalized in rehabilitation care unit for
      treatment of a leg ulcer unhealed for at least 3 months. Clinical, anthropometric
      and biological data were collected on admission. RESULTS: Sixty-six patients,
      mean age 72.9 +/- 16.3 years, were included. Fifty-three p. 100 presented wound
      surfaces over 30 cm(2); 59 p. 100 of the ulcers had lasted for more than one
      year; 62 p. 100 of the ulcers were venous. 48.5 p. 100 of the patients exhibited
      protein malnutrition defined by biological criteria, associated with an
      inflammatory syndrome in 66 p. 100. Anemia and an inflammatory syndrome were
      present in respectively 59 and 58 p. 100 of the patients. Neither anthropometric
      measurements nor nutritional intake or wound characteristics significantly
      differenced between patients with malnutrition or not. Hypoalbuminemia was
      significantly more frequent and severe in patients aged over 70. DISCUSSION:
      Protein malnutrition prevalence is very high in patients with leg ulcers,
      particularly in the elderly. Since nutritional interview or clinical data failed
      to predict protein malnutrition, systematic biological assessment is justified in
      all patients with leg ulcers.

PMID- 12055538
TI  - [Ciclosporin].
AB  - Ciclosporin, produced by the fungus Tolypocladium inflatum GAMS is endowed with
      potent immunosuppressive properties. Ciclosporin interferes with nuclear factors
      of activated T-cells, specifically by preventing cytokine gene transcription,
      particularly interleukin-2, which induces maturation and proliferation of helper
      T-cells. Initially, a traditional formulation of Sandimmun(R) was used, but its
      oral bioavailability varies. Absorption of a new formulation, Neoral(R), is
      significantly better and more reproductible. Ciclosporin has become a major agent
      in the prevention and treatment of organ transplant rejection. It is also
      efficient in treating various immune-related diseases. In dermatology, its
      efficacy has been proven in numerous double-blind, placebo-controlled studies for
      severe psoriasis and atopic dermatitis. Treatment with ciclosporin is also
      beneficial for many dermatologic diseases. However, the effect of this drug has
      principally been studied in open trials and in small cohorts. Ciclosporin
      provokes serious adverse reactions especially nephrotoxicity and arterial
      hypertension. Treatment is occasionally stopped because of these complications.
      The other common side-effects include muco-cutaneous, neurological and gastro
      intestinal symptoms. Increased risk for malignancy is reported with ciclosporin.
      However, in patients with cutaneous diseases, the incidence is low.

PMID- 12055540
TI  - [Acquired dermal melanocytosis: clinical, pathological and ultrastructural
      study].
AB  - INTRODUCTION: Dermal melanocytosis is characterized by the presence of ectopic
      melanocytes in the dermis. There are several clinical forms. This report
      describes an unusual case of acquired dermal melanocytosis probably associated
      with leptomeningeal melanosis. An ultrastructural study was performed. CASE
      REPORT: A 52-year-old Caucasian woman presented with a fifteen-year history of
      slowly spreading gray-blue macular pigmentation, associated with multiple blue
      nevi. Histologic examination revealed dermal melanocytosis. An extracellular
      sheath surrounded the melanocyte and their cytoplasmic processes. Medullar
      magnetic resonance findings were compatible with leptomeningeal melanosis.
      DISCUSSION: Dermal melanocytosis is thought to represent a disorder of neural
      crest migration. Melanocytes are thought to be aberrant and become arrested
      during migration, remaining in the dermis. Reactivation of latent dermal
      melanocytes should explain the pathogenesis of acquired forms. Ultrastructural
      examinations show an extracellular sheath enclosing dermal melanocytes in all
      types of dermal melanocytosis.

PMID- 12055539
TI  - [Facial cellulite associated with mandibular osteomyelitis in an infant].
AB  - INTRODUCTION: The discovery of a jugular tumefaction in an infant evokes several
      diseases. We report the case of a 4-month-old infant whose jugular cellulite
      revealed mandibular osteomyelitis. CASE REPORT: A 4-month-old boy was referred
      for hard, hot tumefaction of the right cheek and multiple cervical adenopathies.
      The suggested diagnosis was cellulite of cutaneous origin. He presented 21
      900/mm(3) hyperleukocytosis associated with an inflammatory biological syndrome.
      Standard x-ray of the facial mass was normal. Sonography of the face showed
      thickening of the soft subcutaneous tissues and retro and sub-mandibular
      adenopathies with abcedation. Antibiotherapy with amoxicillin and clavulanic acid
      led to rapid improvement. Three days after withdrawal of the antibiotherapy, the
      tumefaction recurred without fever. A facial scan eliminated cystic lymphangioma
      and showed osteolysis of the external plateau of the ascending branch of the
      mandible with periosteal appositions. Histological examination of a surgical bone
      biopsy showed infectious osteitis and culture revealed hemolytic beta
      streptococci. Six weeks of antibiotherapy (initially with amoxicillin and
      gentamycin, then amoxicillin in monotherapy) led to the regression of all
      cutaneous signs. COMMENTS: When confronted with a tumefaction in this area,
      malignant or benign tumoral causes such as cystic lymphangioma must be
      eliminated. Infectious causes (abscess, parotid inflammation and osteomyelitis)
      must be evoked and distinguished from infantile cortical hyperostosis (Caffey
      Silverman's syndrome). Standard radiological imaging, scan or scintigraphy are
      useful diagnostic tools. If osteolysis is discovered, a biopsy must be taken for
      anatomopathological and biological examination.

PMID- 12055541
TI  - [Multiple keratoacanthoma centrifugum marginatum].
AB  - INTRODUCTION: Keratoacanthoma centrifugum marginatum is a rare variety of
      commonly isolated keratoacanthoma. The size of the lesions and prolonged
      evolution often raise therapeutic problems. CASE REPORT: A 63-year-old man
      presented with multiple keratoacanthoma centrifugum marginatum evolving for 6
      months and predominating on the lower limbs. Because of the multiplicity and size
      of the lesions, the patient was treated at acitretine at the dose of 1 mg/kg/day
      for five months, leading to the regression of all the lesions. DISCUSSION:
      Keratoacanthoma centrifugum marginatum has rarely been reported in the
      literature. Our observation remains exceptional in the multiplicity and size of
      the lesions. The efficacy of retinoids, previously reported in the treatment of
      solitary giant keratoacanthoma, multiple keratoacanthoma and keratoacanthoma
      centrifugum marginatum, was demonstrated even in this handicapping form of
      keratoacanthoma.

PMID- 12055542
TI  - [Non-congenital smooth muscle hamartoma: 3 cases].
AB  - BACKGROUND: Smooth-muscle hamartoma is an uncommon, usually congenital cutaneous
      hyperplasia of the arrectores pilorum muscles. When it is acquired, it may be
      confused with Becker's nevus with a prominent smooth-muscle component. Both
      entities can be considered polar forms of a spectrum of dermal smooth muscle
      hyperplasia. We report three cases of acquired smooth-muscle hamartoma in adult
      patients. CASE REPORTS: Three healthy women in their fifties presented with adult
      onset asymptomatic, multiple small papules grouped on circumscribed areas of the
      trunk. Results of biopsy specimens showed an excess of haphazardly oriented
      smooth-muscle bundles in the mid to lower dermis with an unremarkable overlying
      epidermis. Immunohistochemical studies showed two components in this
      proliferation: a smooth muscle cell population expressing vimentin and smooth
      muscle actin, and another population of CD34 positive dendritic cells,
      interspersed among the former. DISCUSSION: Proliferation of CD34+ dermal
      dendritic cells has been recently described as an additional component in the
      proliferation of smooth muscle cells, hair follicles and nerve fascicles that
      constitute congenital smooth muscle hamartomas. The results of
      immunohistochemical studies in our three cases extend this observation to the
      acquired variant of cutaneous smooth muscle hamartoma, which can be included in
      the expanding spectrum of diseases, recently characterized by the presence of a
      dermal proliferation of CD34 + cells.

PMID- 12055543
TI  - [Retroperitoneal fibrosis secondary to metastatic neoplasm revealed by a leg
      lymphedema].
AB  - INTRODUCTION: Diagnosis of retroperitoneal fibrosis is generally delayed and
      revealed by various non-specific signs. We report the case of an isolated
      lymphedema of the lower limb revealing retroperitoneal fibrosis complicating a
      metastatic squamous cell carcinoma. CASE REPORT: In an 83-year-old women, a
      lymphedema appeared that remained isolated for several months before being
      associated with alteration in general health. Morphological examinations showed
      bilateral compression of the urinary excretory tracts and led to the diagnosis of
      retroperitoneal fibrosis. Histological examination of a sub-clavicular adenopathy
      that had evolved over 9 months, confirmed the diagnosis of a metastatic squamous
      cell carcinoma of pulmonary cancer. DISCUSSION: Retroperitoneal fibrosis is an
      exceptional etiology that must be recognized in isolated lymphadomas of the lower
      limbs. In view of the possible tumoral origin of retroperitoneal fibrosis, any
      evocative sign accompanying the lymphedema must be searched for.

PMID- 12055544
TI  - [Trumpet nail deformity during the course of Dowling-Meara type epidermolysis
      bullosa simplex. A report of two cases].
AB  - INTRODUCTION: We report two patients with Dowling-Meara type epidermolysis
      bullosa simplex: who had trumpet nail deformity. CASE REPORTS: Two 75 and 72 year
      old sisters, had flare-ups of epidermolysis bullosa simplex since childhood. The
      aspect of the lesions and electron microscopy were in favour of the diagnosis of
      the Dowling-Meara variant of epidermolysis bullosa simplex. Both women had
      several fingernails with pincer and trumpet nail deformities. There were no such
      signs among the other siblings, who had never had epidermolysis. DISCUSSION: Nail
      involvement is not rare during the course of superficial epidermolysis bullosa.
      The trumpet lesions appear to be relatively specific to the present two cases of
      epidermolysis bullosa simplex. The electron microscopic findings of these two
      cases were also noteworthy, with whisk-like but not round clumping of the
      perinuclear tonofilaments.

PMID- 12055545
TI  - [Severe humoral hypercalcemia, elevated level of parathyroid hormone-related
      protein (PTH-rp) and cutaneous squamous cell carcinoma].

PMID- 12055546
TI  - [Unilateral atrophoderma following Blaschko's lines: Blaschkolinear morphoea or
      Moulin's linear atrophoderma?].

PMID- 12055547
TI  - [Cellulitis and necrosing fascitis].

PMID- 12055548
TI  - [Pyogenic granuloma recurring with multiple satellites: Nd: YAG laser treatment
      with ice cube cooling].

PMID- 12055549
TI  - [Human papillomavirus (HPV) induced lesions in HIV-positive individuals after
      highly active antiretroviral therapy].

PMID- 12055550
TI  - [Atonic ulceration of the ankle].

PMID- 12055551
TI  - [A facial nodule].

PMID- 12055552
TI  - [Hyperpigmentation on black skin].

PMID- 12055553
TI  - [The use of psychotropics drugs in dermatology].

PMID- 12055554
TI  - [Superficial cervical plexus, spinal nerve and external jugular vein].

PMID- 12055555
TI  - [Accurate and precise].

PMID- 12055556
TI  - [Cutis verticis gyrata].

PMID- 12055557
TI  - [Gunther's erythropoietic porphyria].

PMID- 12055558
TI  - [Recurrent erythema annulare-type vasculitis].

PMID- 12055559
TI  - [The first case of lasting pigmented toxidermia induced by cetirizine (Zyrtec,
      Virlix) and ticlopidine].

PMID- 12055560
TI  - Evaluation of kangaroo pericardium as an alternative substitute for
      reconstructive cardiac surgery.
AB  - BACKGROUND: Bioprosthetic materials (human, bovine and porcine) are used in
      various cardio-thoracic repair and replacement procedures because of excellent
      performance and low thrombogenicity. These bioprosthetic substitutes fail due to
      degeneration and calcification. This study examines the morphology, tensile
      properties and calcification potential of kangaroo pericardium in vitro and in
      vivo. METHODS: Bovine (control tissue) and kangaroo pericardium, fixed in 0.625%
      buffered glutaraldehyde, were examined by light and scanning electron microscopy.
      A standard method was used for biaxial testing. Pericardial strips (10 x 5 mm)
      were implanted subcutaneously into male Wistar rats and retrieved after 4, 6 and
      8 weeks and examined by Von Kossa's stain technique and atomic absorption
      spectrophotometry. RESULTS: Histology revealed serosa and fibrosa cell layers in
      both tissues. Electron microscopy showed a densely arranged collagen matrix in
      kangaroo pericardium. Kangaroo pericardium calcified significantly less than
      bovine pericardium at 4 weeks (0.80+/-0.28 versus 21.60+/-4.80 microg/mg) at 6
      weeks (0.48+/-0.08 versus 32.80+/-14.4 microg/mg) and at 8 weeks (2.40+/-1.20
      versus 30.40+/-17.20 microg/mg), respectively. CONCLUSIONS: Kangaroo pericardium
      has a densely arranged collagen matrix with a higher extensibility and
      significantly lower calcification potential. Therefore, kangaroo pericardium
      could be used as an alternative substitute in cardiac surgery because of its low
      calcification potential.

PMID- 12055561
TI  - Off-pump coronary bypass grafting to double vessel disease with the
      pharmacological assist of esmolol. An experimental study.
AB  - BACKGROUND: To demonstrate the surgical efficacy and safety of off-pump coronary
      bypass grafting to double- or triple-vessel disease, we performed off-pump double
      bypass grafting using a brief local coronary occlusion with the pharmacological
      assist of esmolol. METHODS: These experiments were conducted in 30 canine hearts
      with the left internal thoracic artery (ITA) grafted to the circumflex coronary
      artery (CFX) and the right ITA grafted to the left anterior descending coronary
      artery (LAD), off pump, using a brief local coronary occlusion through the left
      minithoracotomy. The coronary anastomosis was performed using a brief local
      occlusion of the coronary artery. An anastomosis between the left ITA and the CFX
      was done first, and then the right ITA and the LAD were anastomosed. Thirty
      animals were divided into 2 groups, group A (n=15) receiving esmolol just before
      (10 mg/kg on a bolus) and during the coronary artery occlusion (500 microg/kg/min
      continuously), and group B (n=15) without administrating esmolol as a control.
      RESULTS: Operative deaths were 4 in group B and all of group A animals survived
      (p<0.05). All deaths were attributable to ventricular arrhythmias during/after
      coronary occlusion. Group B animals necessitating longer coronary occlusion time
      (more than 15 min) were more likely to fibrillate and more difficult to
      resuscitate than group A animals requiring coronary occlusion time more than 15
      min. Segmental shortening on the echocardiogram demonstrated no significant
      difference between group A and B in both anterior and posterior wall segment.
      However, echocardiogram in animals necessitating coronary occlusion time more
      than 15 min demonstrated that segmental shortening in group A were better than in
      group B (18 vs 11%, p<0.05), and comparatively greater but not significant in the
      posterior wall (19 vs 14%). CONCLUSIONS: The use of esmolol may be recommended to
      off-pump coronary bypass even to the double-vessel bypass, in order to make off
      pump approach safer.

PMID- 12055562
TI  - Hemodynamic performance after stented vs stentless aortic valve replacement.
AB  - BACKGROUND: Stentless bioprostheses are anticipated to cause improved
      hemodynamics and increased longevity over stented bioprosthesis. We have compared
      echocardiographic analysis of stented bioprosthesis "Freestyle" with stented
      "Mosaic" bioprosthesis. Because of similar technology (0 pressure fixation,
      anticalcification) any differences may relate to stent. METHODS: Twenty-eight
      patients undergoing AVR were randomly assigned to receive either stented or
      stentless. Echocardiograms, by means of M-mode and Doppler were performed early,
      3-6 months and 1 year postoperatively. RESULTS: The peak flow velocity was
      significantly lower in the stentless group, especially 1 week and 6 months after
      surgery. Mean transvalvular gradient dropped significantly in stentless group and
      did not change in stented group. EOA did not change significantly in either of
      groups. AoV velocity time integral was increasing in stentless group. LV mass had
      fallen significantly in both groups but degree of mass reduction was comparable.
      CONCLUSIONS: There are marked improvements of stentless valves hemodynamics.
      However it is not necessary equal to higher degree of LV mass reduction during 1
      year follow-up.

PMID- 12055563
TI  - Ischemic preconditioning protects right ventricular function in coronary artery
      bypass grafting patients experiencing angina within 48-72 hours.
AB  - BACKGROUND: To test whether ischemic preconditioning (IP) is able to protect the
      myocardium in recently unstable CABG patients. METHODS:  EXPERIMENTAL DESIGN:
      prospective, randomised, controlled clinical study. SETTING: University Hospital.
      PATIENTS: Forty CABG patients with recent unstable angina were randomised into an
      IP group (n=20) and a control group (n=20). Subgroup was divided based on the
      time of the most recent ischemia onset before the operation. INTERVENTION: The IP
      group was preconditioned with 2 cycles of 2-min ischemia followed by 3-min
      reperfusion before cross clamping. MEASURES: Hemodynamic data were monitored till
      the 1st POD. Biochemical markers were measured till the 2nd POD. RESULTS: There
      were no differences in cardiac index (Cl) and right ventricular ejection fraction
      (RVEF) in patients experiencing angina within 48 hours prior to operation. The
      percentage changes in CI and RVEF at 1 hour after declamping were significantly
      better in the IP group in patients experienced angina within 48-72 hours (106% vs
      88% of baseline, p=0.027 and 103% vs 81% of baseline, p=0.023). No difference in
      postoperative cardiac troponin I (CTnI) and CK-MB was found between the IP and
      controls in either subgroup. CONCLUSIONS: IP has a beneficial effect on global
      and right ventricular hemodynamic functional recovery in unstable CABG patients
      experiencing angina within 48-72 hours prior to the operation. However, IP has no
      additional protective effects in unstable CABG patients who experience angina
      within 48 hours.

PMID- 12055564
TI  - Surgical repair for degenerative and rheumatic mitral valve disease. Operative
      and mid-term results.
AB  - BACKGROUND: Non randomized studies suggest that mitral valve repair for rheumatic
      disease is technically more difficult than repair for degenerative disease, and
      that operative and late results are worse. New surgical techniques have been
      developed in our and other institutes during the last 5 years, and this moved us
      to review the experience with these two pathologies and to compare the operative
      and mid-term RESULTS:  METHODS: From March 1996 to September 1997, 66 patients
      underwent primary mitral valve repair for treatment of degenerative or rheumatic
      disease. Fifty-two patients (79%) were in the former group (group A) and 14 in
      the latter (group B). Surgery was performed by 2 experienced cardiac surgeons. A
      new technique to calculate the exact artificial chordae length was introduced. In
      2 cases, tricuspid autografts were transposed to mitral position and reinforced
      with artificial chordae. Patients were followed both clinically and
      echocardiographically. The follow-up data were collected in a 1-month period (May
      2000). The average clinical follow-up was 3.1+/-0.9 years (range 1.7 to 4.2
      years) while the average echocardiographic follow-up was 2.7+/-0.7 years (range 9
      months to 4 years). All values were expressed by means of the average and
      standard deviation. chi(2) and Student's "t"-test were used to analyze the
      significance between variables. The Kaplan-Meyer method was used for actuarial
      statistics. RESULTS: There were no operative deaths in either group. In group A,
      1 patient underwent a second surgical repair 1 week later, successfully. In group
      B no patients underwent reoperation within 30 days or during the initial
      hospitalization. At follow-up of group A there were the following events: deaths
      from cancer (n=2), endocarditis (n=1), aortic dissection (n=1). At follow-up of
      group B there were mitral valve replacement (1 year after first operation, n=1),
      Ross procedure (n=1), ischemic heart failure (n=1). Among the remaining 62
      patients followed, 32 were in NYHA class I, 15 in class II, 3 in class III, and
      none in class IV, in group A. In group B, 7 patients were in class I, 4 in class
      II, 1 in class III and none in class IV (p=ns). In group A mitral regurgitation
      was absent in 23 patients, mild in 21, moderate in 6, while in group B it was
      absent in 4, mild in 6, and moderate in 2 (p=ns). In both groups there were no
      cases of severe insufficiency. The mean gradient was 1.1+/-1.7 mmHg in group A
      (median=0), and 2.4+/-3.1 mmHg in group B (median=0), (p=ns). No case of systolic
      anterior movement was seen at mid-term. The event free-survival rate was 92.8% in
      group A and 92.3% in B. CONCLUSIONS: Perfecting and innovation of surgical
      techniques make possible nowadays to reach good and equivalent operative and mid
      term results in both pathologies.

PMID- 12055566
TI  - Ruptured abdominal aortic aneurysm. Time for a new approach.

PMID- 12055565
TI  - Factors influencing immediate and long-term results after button's technique.
AB  - BACKGROUND: Aim of this study was to evaluate the factors influencing immediate
      and long-term results in patients undergoing aortic root replacement with a
      composite graft. METHODS: Between January 1989 and February 1999, 105 patients
      (83 males, 22 females) who underwent Bentall technique were studied. Preoperative
      diagnosis was annulo-aortic ectasia in 54, aortic dissection in 27,
      atherosclerotic aneurysm in 21, and aortitis in 3 cases. Seventeen patients were
      affected by Marfan's syndrome. All cases, elective, urgent, and emergency were
      included. Button technique was performed and the associated surgical procedures
      were coronary artery bypass grafting in 21, total aortic arch replacement in 15,
      proximal hemi arch in 5, and mitral valve replacement in 5 cases. RESULTS: The
      overall hospital mortality rate was 7.6% (n=8). Univariate analysis using chi(2)
      and/or two-sample "t"-test showed that dissection, aortitis, aneurysm rupture
      into-pleura or pericardium, emergency status, redo, prolonged pump times and
      circulatory arrest, were predictors influencing in-hospital mortality.
      Coagulopathy, low cardiac output, stroke, perioperative myocardial infarction,
      surgical bleeding leading to reoperation, were significantly related to in
      hospital mortality (by correlation analysis). A multivariate analysis showed
      that, emergency status (p=0.027), aortic dissection (p=0.029), perioperative
      myocardial infarction (p=0.0021), reoperation for bleeding (p=0.0023), and pump
      time >180 min (p=0.011), were significant. The actuarial survival rate at 10
      years follow-up was 84.7%. There were 8 late deaths. The Kaplan-Meier showed
      significant differences when considering dissection vs non-dissection (p=0.018),
      but did not reach significance in Marfan vs non-Marfan groups (p=0.83). NYHA
      class IV (p=0.052), previous cardiac surgery procedure (p=0.041), concomitant
      CABG (p=0.021), total aortic arch reconstruction (p=0.001), and mitral valve
      replacement (p=0.016), were identified as significant by Log Rank test.
      CONCLUSIONS: The Bentall procedure for aortic root replacement is safe and
      durable; in hospital mortality in elective status it was 1.28%; early and long
      term mortality higher in patients with acute dissection. Six late deaths were
      procedures related. Sixty-six patients (76.4%) were in NYHA I class at follow-up.
      The incidence of late outcomes, thromboembolism (1.03%), graft infection (2.06%),
      pseudoaneurysm (0%), reoperation in ascending aorta or aortic valve (3.1%),
      operations on the remaining aorta (6.7%), and hemorrhage due to anticoagulant
      therapy (1.03%), are very low.

PMID- 12055567
TI  - Vascular restenosis. Basic science and clinical implications.
AB  - Cardiovascular interventions to correct arterial occlusive disease have excellent
      short-term results, but long-term patency is still seriously compromised by the
      development of restenosis. This review will provide a portrait of the mechanisms
      following vascular injury, define the clinical scope of the problem and outline
      developments of different therapeutical strategies to prevent restenosis.

PMID- 12055568
TI  - Endovascular abdominal aortic aneurysm (AAA) repair since the FDA approval. Are
      we going too far?
AB  - BACKGROUND: Since the FDA approval of endovascular devices for abdominal aortic
      aneurysm (AAA) repair, clinicians have been relaxing the strict inclusion
      criteria of the clinical trials. We have reviewed our experience during and after
      the clinical trials to examine changes in patient selection, technical aspects of
      the procedure, and outcome. METHODS: A review of a prospectively compiled
      database of all endovascular AAA repairs performed at our institution was
      performed. RESULTS: Endovascular AAA repair was attempted in 130 patients: 46
      (35.4%) as a part of clinical trials (Group I), and 84 (64.6%) since the FDA
      approval of the devices (Group II). Significant differences in patient selection
      included: a higher proportion of short (<15 mm) proximal necks in Group II (28.6
      vs 0.0%, p<0.001), and a higher proportion of iliac occlusive disease in Group II
      (48.8 vs 15.4%, p=0.001). Additional trends suggested that Group II AAA's were
      more complex, including increased proximal neck angulation, increased proximal
      calcification, increased presence of proximal thrombus, and increased iliac
      tortuosity. Significant differences in technical aspects of the procedure
      included increased usage of iliac angioplasty (46.4 vs 13.3%, p<0.001), iliac
      stenting (31 vs 8.9%, p<0.01), and conduit access to the external iliac artery
      (10.7 vs 0%, p=0.03) in Group II. Analysis of outcome revealed a decreased
      incidence of the following in Group II cases: conversions to open repair (2.4 vs
      10.9%), lower extremity ischemia (3.6 vs 13.0%), and graft limb occlusion (2.4 vs
      8.7%). Other major perioperative complications did not differ significantly
      between the 2 groups. However, although the overall rate of any endoleak noted in
      the postoperative course was decreased in Group II cases (26.2 vs 32.6%), the
      incidence of proximal or distal attachment site leaks has increased (11.9 vs
      4.3%, p=0.14). Although this comparison did not reach statistical significance,
      the magnitude of the increase is concerning. CONCLUSIONS: Although we have been
      able to offer endovascular AAA repair to a larger number of patients since FDA
      approval, endovascular management of increasingly complex proximal necks and
      increased iliac artery disease appears to have increased the incidence of
      attachment site endoleaks. Although many of these leaks have been successfully
      managed with adjunctive endovascular procedures, their increasing incidence is
      worrisome and suggests that we may need to re-evaluate current inclusion criteria
      for using this technology. Although difficult access issues have been handled
      with adjunctive procedures, the presence of a short, angulated proximal neck may
      be difficult to overcome, and may not be well suited for endovascular repair with
      the currently available devices.

PMID- 12055569
TI  - Endovascular approaches to ruptured infrarenal aorto-iliac aneurysms.
AB  - BACKGROUND: Ruptured abdominal aortoiliac aneurysms (RAAAs) carry a high
      mortality when treated by open surgical repair. Since 1994, we have employed
      endovascular approaches to treat this entity. METHODS: Patients with presumed
      RAAAs were treated with restricted fluid resuscitation (hypotensive hemostasis),
      rapid transport to the operating room, placement of a transbrachial or
      transfemoral guidewire under local anesthesia, and urgent arteriography. In
      patients with suitable anatomy, endovascular graft repair was performed. If the
      anatomy was unsuitable, standard open repair was performed. If the patient had
      circulatory collapse, proximal balloon control was employed. RESULTS: Of 31
      patients managed in this fashion, 25 underwent endovascular graft repair. Six
      required open repair. Total operative mortality was 9.7% (3 patients). Only 10
      patients required proximal balloon aortic control. CONCLUSIONS: Endovascular
      techniques (proximal balloon control and endografts) may improve treatment
      outcomes for RAAAs. Restricted resuscitation (hypotensive hemostasis) can be
      effective in the RAAA setting.

PMID- 12055570
TI  - The Dutch Randomised Endovascular Aneurysm Management (DREAM) trial. Background,
      design and methods.
AB  - After the introduction of endovascular repair of abdominal aortic aneurysms
      (AAA), both benefits and drawbacks of this new technique have been reported. To
      assess whether the new technique is an adequate substitute of conventional AAA
      repair, a randomised study is due. The Dutch Randomised Endovascular Aneurysm
      Management (DREAM) trial is a randomised multicenter trial enrolling patients
      eligible for elective treatment of infrarenal AAAs. In this study, the cost
      effectiveness of endovascular aneurysm repair (EAR) is compared with that of
      conventional transabdominal surgery, in patients that are considered suitable for
      both types of treatment. The primary endpoint is combined operative mortality and
      morbidity. Secondary endpoints and additional assessments include event free
      survival, quality of life, length of hospital stay and costs. It is expected that
      the DREAM-trial will lead to a safe and controlled introduction of a new
      technology. Also, the medical community will obtain valid scientific evidence of
      the merits of endovascular AAA repair. Finally, policy makers will be provided
      with accurate cost-effectiveness data for the Dutch healthcare system. The aim of
      the present paper is to describe the background, methods and design of the DREAM
      trial.

PMID- 12055571
TI  - Combined surgical approach for carotid and coronary stenosis. Sixty-four patients
      and review of literature.
AB  - BACKGROUND: The proper role of combined carotid endarterectomy (CEA) and coronary
      bypass (CABG) is still controversial. We contribute to the discussion through the
      critical evaluation of 64 consecutive patients, whose data have been collected in
      a prospective way. METHODS: Between 1990 and 1999, 64 patients presenting a
      critical coronary disease (unemendable by PTA) associated with severe carotid
      stenosis (= or >70% if symptomatic, = or >80% if asymptomatic), underwent
      combined CEA-CABG. Cardiological symptoms were evident in 90.6% of cases. Thirty
      five patients (54.7%) had a three-vessel coronaropathy, 18 (28.1%) a two-vessel
      disease and 11 (17.2%) severe stenosis of the common trunk; furthermore 7
      patients (10.9%) had a low ejection fraction (<50%). A positive neurologic
      history was present in 22 (44%) patients. Thirty-four patients (55%) had a
      carotid stenosis >90%; a significant disease of the contralateral carotid axis
      was observed in 53% of cases: stenosis >50% in 30 patients and thrombosis in 4.
      CEA was performed with somato-sensorial evoked potential monitoring. RESULTS: The
      hospital mortality rate was 6.2% (4 patients). The cause of death was cardiac in
      2 cases (1 early bypass thrombosis and 1 irreversible coronary spasm) and related
      to a multiorgan failure in 2. The neurologic morbidity rate was 0%. CONCLUSIONS:
      Our data highlight that in these high-risk patients the combined approach
      dramatically reduces the stroke risk although the mortality rate is still higher
      than that observed after CEA or CABG.

PMID- 12055572
TI  - Prospective comparative study of two cerebral protection devices in carotid
      angioplasty and stenting.
AB  - BACKGROUND: The aim of the study was to compare two of the available cerebral
      protection devices (CPD) PercuSurge, balloon type (group A) and Angioguard,
      filter type (group B) used in carotid stenting and angioplasty (CAS). METHODS:
      From September 1999 to February 2001, 26 consecutive patients undergoing CAS were
      alternatively assigned to group A and B. Postoperative disabling stroke and
      neurological mortality, nondisabling stroke, TIA and non-neurological mortality
      were examined. CPD features included time required, ease of handling, device
      rupture or malfunctioning, radiopaque markers evidence, abnormal major mobility
      of the opened system. RESULTS: RNCR was 0 and TIAs were not observed in either
      group. Four patients (3 in group A and 1 in group B) showed drowsiness in the
      immediate postoperative period. Perioperative carotid occlusion and surgical
      conversion were observed in 1 case of group A. Average time calculated from the
      beginning of set-up to complete removal was 46 min in group A versus 31 min in
      group B. Abnormal major mobility of the opened system was very often observed
      during endovascular maneuvers with both devices. CONCLUSIONS: CAS may protect
      against postoperative procedure-related neurological events. Common and specific
      disadvantages were observed in both systems showing they were not close enough to
      the ideal device.

PMID- 12055573
TI  - Adventitial cystic disease of the popliteal artery: diagnosis and treatment. A
      case report.
AB  - Adventitial cystic disease of the popliteal artery (ACDPA) is an unusual cause of
      a unilateral progressive intermittent claudication in young or middle-aged men.
      In the case described here, ultrasound (US) examination provided the preoperative
      diagnosis. The lesion was dealt with by simple evacuation of the cyst and
      excision of the wall. This simple treatment is all that is required in the
      majority of cases and provides good long-term results.

PMID- 12055574
TI  - Alternative approach to endoluminal treatment of an anastomotic aneurysm.
AB  - Conventional surgical treatment of patients with an anastomotic aneurysm can be a
      surgical challenge if severe adhesions are present. We report here effective
      treatment of an anastomotic aneurysm using an endoluminal stent graft. A 71-year
      old man had undergone an aorto-bifemoral bypass for Leriche's syndrome in 1989
      and partial gastrectomy for cancer in 1996. He was admitted to our department
      with a pseudoaneurysm of a proximal anastomosis located at the aorta below both
      renal arteries. Based on his medico-surgical history, we considered that an
      endovascular stent should be placed. This graft composed of an UBE(UBE-WOVEN
      GRAFT) graft and self-expandable Z stents were introduced through the right limb
      of the bifurcated graft previously implanted, then were placed using the delivery
      system while advancing under fluoroscopic control, using a pusher rod.
      Endoleakage was not evident and the postoperative course was uneventful. An
      endovascular graft is one alternative approach for treating patients with an
      anastomotic aneurysm as it is less invasive. This procedure proved satisfactory
      for this patient.

PMID- 12055575
TI  - 8th international workshop of endovascular surgery. Aortic aneurysms endovascular
      treatment. Ajaccio (France), June 15-17, 2001.

PMID- 12055576
TI  - Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype
      is increased in hepatitis C.
AB  - BACKGROUND & AIMS: A homozygous 32-base pair deletion in the CCR5 gene (CCR5
      Delta32) protects against human immunodeficiency virus infection (HIV). However,
      the role of this mutation in other infections, such as hepatitis C virus (HCV)
      infection, has not been defined. METHODS: We determined the frequency of the CCR5
      Delta32 mutation by polymerase chain reaction in anti-HCV(+) (n = 153), anti
      HIV(+) (n = 102), and anti-HCV(+)/HIV(+) (n = 130) white patients as well as in
      102 healthy blood donors. Then, HIV and HCV loads, aminotransferases, and CD4 and
      CD8 cell counts were compared between the resulting subsets of CCR5-Delta32/wild
      type heterozygotes, CCR5-Delta32, and wild-type homozygotes, respectively.
      RESULTS: Twelve of 153 (7.8%) anti-HCV-seropositive patients and 1 of 102 (1.0%)
      healthy blood donors were CCR5-Delta32 homozygous, whereas CCR5-Delta32
      homozygosity was absent in anti-HIV(+) and anti-HCV(+)/HIV(+) patients (P <
      0.001). The frequency of the CCR5-Delta32 allele was higher in the anti-HCV(+)
      (16.0%, P < 0.05) and anti-HCV(+)/HIV(+) (12.7%, NS) patients than in healthy
      blood donors (8.3%) and anti-HIV(+) patients (9.3%), respectively. Anti-HCV(+)
      CCR5-Delta32 homozygotes occurred 3 times more frequently than expected from the
      Hardy-Weinberg equation (P < 0.0001) and had significantly higher HCV loads than
      wild-type patients (P = 0.045). CONCLUSIONS: The increased prevalence of CCR5
      Delta32 homozygosity associated with increased viral loads in patients with
      chronic hepatitis C suggests that the CCR5-Delta32 mutation may be an adverse
      host factor in hepatitis C.

PMID- 12055577
TI  - The gluten response in children with celiac disease is directed toward multiple
      gliadin and glutenin peptides.
AB  - BACKGROUND & AIMS: Gluten (GLU)-specific T-cell responses in HLA-DQ2 positive
      adult celiac disease (CD) patients are directed to an immunodominant alpha
      gliadin (GLIA) peptide that requires deamidation for T-cell recognition. The aim
      of the current study was to determine which GLU peptide(s) are involved early in
      disease. METHODS: We have characterized the GLU-specific T-cell response in HLA
      DQ2 positive children with recent onset CD. RESULTS: We found that 50% of these
      patients do not respond to the alpha-GLIA peptide but to a diverse set of GLIA
      and glutenin (GLT) peptides, including 6 novel epitopes. Moreover, individual
      patients respond to distinct (combinations of) GLU peptides. T-cell cross
      reactivity toward homologous GLIA and GLT peptides was observed, which might play
      a role in the initial spreading of the GLU-specific T-cell response. Although all
      pediatric patients displayed deamidation-dependent responses, deamidation
      independent responses were found in the majority of patients as well. Finally, T
      cell responses to 3 of these novel GLU peptides were found in adult CD patients.
      CONCLUSIONS: The diversity of the GLU-specific T-cell response is far greater
      than was previously appreciated. Both adult and young CD patients can respond to
      a diverse repertoire of GLU peptides. The observation that T-cell responses to 3
      of the novel peptides are independent of deamidation indicates that T-cell
      responses can be initiated toward native GLU peptides. The possibility that
      deamidation drives the GLU response toward immunodominant T-cell stimulatory
      peptides after disease initiation is discussed.

PMID- 12055578
TI  - Friedenwald of the Friedenwald award.

PMID- 12055579
TI  - Clinical and pathophysiological characteristics of acute-onset functional
      dyspepsia.
AB  - BACKGROUND & AIMS: Functional bowel disorders may follow acute intestinal
      infection. In animals, postinflammatory dysmotility is associated with nitrergic
      dysfunction. The aim of this study was to identify and characterize patients with
      presumed postinfectious dyspepsia (PD) compared with unspecified-onset dyspepsia
      (UD). METHODS: A total of 400 consecutive dyspeptic patients filled out a
      questionnaire to assess whether their symptoms were of postinfectious origin.
      They underwent testing for Helicobacter pylori infection as well as gastric
      emptying and gastric barostat studies. Pharmacological studies of nitrergic
      gastric function were performed in controls, in patients with presumed PD, and in
      patients with UD using sumatriptan, an activator of nitrergic neurons, and
      amylnitrite, a nitric oxide donor. RESULTS: Presumed PD was present in 17% of the
      patients and associated with more prevalent early satiety, weight loss, nausea,
      and vomiting compared with UD. Both groups did not differ in H. pylori infection,
      gastric emptying, or gastric sensitivity. Impaired accommodation was
      significantly more prevalent in patients with presumed PD (67% vs. 30%; P <
      0.05). Sumatriptan relaxed the stomach in controls and patients with UD but not
      in patients with presumed PD, whereas amyl nitrite relaxed the stomach in all
      subjects. CONCLUSIONS: A subset of dyspeptic patients has a history suggestive of
      postinfectious dyspepsia. These patients have a high prevalence of impaired
      accommodation attributable to a dysfunction at the level of gastric nitrergic
      neurons.

PMID- 12055580
TI  - Prokinetic effects in patients with intestinal gas retention.
AB  - BACKGROUND & AIMS: We have previously shown that patients with irritable bowel
      syndrome (IBS) have impaired transit of intestinal gas loads. Because abnormal
      gas retention can be experimentally reproduced in healthy subjects by
      pharmacological inhibition of gut motility, we hypothesized that impaired gas
      transit and retention can be reciprocally corrected by pharmacologically
      stimulating intestinal propulsion. METHODS: In 28 patients with abdominal
      bloating (14 IBS, 14 functional bloating) and in 14 healthy subjects, gas
      evacuation and perception of jejunal gas infusion (12 mL/min) were measured.
      After 2 hours, in 20 patients we tested the effect of intravenous neostigmine
      (0.5 mg) vs. intravenous saline administered blindly and randomly at a 1-hour
      interval. RESULTS: After 2 hours of gas infusion, patients with IBS and
      functional bloating alike exhibited significant gas retention (418 +/- 86 mL),
      abdominal symptoms (2.7 +/- 0.5 score), and objective distention (8 +/- 2 mm
      girth increment), in contrast to healthy controls, who experienced none (46 +/-
      102 mL retention, 0.4 +/- 0.3 symptom score, and 3 +/- 1 mm distention; P < 0.05
      for all). Neostigmine produced immediate clearance of gas retained within the gut
      (603 +/- 53 mL/30 minutes vs. 273 +/- 59 mL/30 minutes after saline; P < 0.05)
      and by 1 hour reduced gas retention (by 373 +/- 57 mL), abdominal symptoms (by
      1.1 +/- 0.5 score), and distention (by 6 +/- 1 mm; P < 0.05 for all), whereas
      intravenous saline produced no effects. CONCLUSIONS: In patients with intestinal
      gas retention, pharmacological stimulation of intestinal propulsion improves gas
      transit, abdominal symptoms, and distention.

PMID- 12055581
TI  - Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion
      compared with hepatitis B virus genotype C.
AB  - BACKGROUND & AIMS: Recent studies suggest that hepatitis B virus (HBV) genotype B
      is associated with less active liver disease than HBV genotype C. The aim of our
      study was to determine if HBV genotype B is associated with higher rates of
      spontaneous hepatitis B e antigen (HBeAg) seroconversion compared with genotype
      C. METHODS: A retrospective study using stored sera from 332 Chinese patients
      with chronic HBV infection followed for a mean of 48 months (range, 12-98) were
      tested for HBV genotype using a line-probe assay. RESULTS: HBV DNA was detected
      in 273 patients, 122 had HBV genotype B and 147 genotype C. Patients with
      genotype B had a significantly lower prevalence of HBeAg at presentation and
      significantly higher rates of spontaneous HBeAg seroconversion during follow-up.
      HBV genotype B patients who were HBeAg positive were significantly younger, and
      spontaneous HBeAg seroconversion occurred approximately 1 decade earlier compared
      with HBV genotype C patients. Multivariate analyses identified high alanine
      aminotransferase (baseline and follow-up), age >30 years, and genotype B as
      independent factors associated with spontaneous HBeAg seroconversion.
      CONCLUSIONS: HBV genotype B is associated with earlier HBeAg seroconversion than
      genotype C. This finding may explain the less active/progressive liver disease in
      patients with genotype B.

PMID- 12055582
TI  - A randomized controlled trial of preoperative oral supplementation with a
      specialized diet in patients with gastrointestinal cancer.
AB  - BACKGROUND & AIMS: Perioperative nutrition with specialized enteral diets
      improves outcome when compared with standard formulas. A post-hoc analysis
      suggested preoperative administration as the most important period. Thus, we
      designed a study to understand prospectively whether preoperative supplementation
      could be as efficacious as the perioperative approach and superior to a
      conventional treatment (no artificial nutrition) in reducing postoperative
      infections and length of hospital stay. METHODS: A total of 305 patients with
      preoperative weight loss <10% and cancer of the gastrointestinal tract were
      randomized to receive the following: (1) oral supplementation for 5 days before
      surgery with 1 L/day of a formula enriched with arginine, omega-3 fatty acids,
      and RNA, with no nutritional support given after surgery (preoperative group, n =
      102); (2) the same preoperative treatment plus postoperative jejunal infusion
      with the same enriched formula (perioperative group, n = 101); and (3) no
      artificial nutrition before and after surgery (conventional group; n = 102).
      RESULTS: The 3 groups were comparable for all baseline and surgical
      characteristics. Intention-to-treat analysis showed a 13.7% incidence of
      postoperative infections in the preoperative group, 15.8% in the perioperative
      group, and 30.4% in the conventional group (P = 0.006 vs. preoperative; P = 0.02
      vs. perioperative). Length of hospital stay was 11.6 +/- 4.7 days in the
      preoperative group, 12.2 +/- 4.1 days in the perioperative group, and 14.0 +/-
      7.7 days in the conventional group (P = 0.008 vs. preoperative and P = 0.03 vs.
      perioperative). CONCLUSIONS: Preoperative supplementation is as effective as
      perioperative administration in improving outcome. Both strategies seem superior
      to the conventional approach.

PMID- 12055583
TI  - Rectal distention testing in patients with irritable bowel syndrome: sensitivity,
      specificity, and predictive values of pain sensory thresholds.
AB  - BACKGROUND & AIMS: Visceral hypersensitivity was detected in patients with
      functional gastrointestinal disorders and has been proposed as a biological
      marker of irritable bowel syndrome (IBS). The purpose of this study was to assess
      the sensitivity, specificity, and the predictive values of pain thresholds
      evaluated by rectal distention using an electronic barostat in patients with or
      without IBS and in control subjects. METHODS: Patients were diagnosed according
      to Rome II criteria. Rectal sensory thresholds were determined in 164 patients
      (86 IBS patients, 26 painless constipation, 21 functional dyspepsia, and 31
      miscellaneous conditions) and in 25 normal controls. All subjects underwent a
      series of rectal isobaric distentions using an electronic barostat. The bag was
      progressively distended from 0 to 48 mm Hg and, in response to distention,
      subjects reported on discomfort or pain. RESULTS: Pain thresholds were lower in
      IBS patients (30.4 +/- 6.7 mm Hg) compared with controls (44.5 +/- 5), painless
      constipated (45.4 +/- 5.3), functional dyspepsia (39.4 +/- 7.8), and
      miscellaneous patients (43.2 +/- 5.5). At the level of 40 mm Hg, the sensitivity
      of the rectal barostat to identify IBS patients from normal subjects and non-IBS
      patients was 95.5% and its specificity was 71.8%. The positive predictive value
      was 85.4%. The negative predictive value was 90.2%. CONCLUSIONS: Lowered rectal
      pain threshold is a hallmark of IBS patients. Rectal barostat testing is useful
      to confirm the diagnosis of IBS and to discriminate IBS from other causes of
      abdominal pain.

PMID- 12055584
TI  - Activation of the mucosal immune system in irritable bowel syndrome.
AB  - BACKGROUND & AIMS: A role for the mucosal immune system in the pathogenesis of
      irritable bowel syndrome is suggested by its association with intestinal
      infections. METHODS: To investigate this, we performed histologic and
      immunohistologic studies on colonoscopic biopsy specimens from 77 patients with
      symptoms satisfying the Rome criteria and 28 asymptomatic control patients.
      RESULTS: Histologic assessment of biopsy specimens from symptomatic patients
      indicated 3 different groups. The first (38 of 77) had normal conventional
      histology; however, immunohistology showed increased intraepithelial lymphocytes
      (median, 1.8-fold; range, 1.74-1.86), lamina propria CD3(+) cells (2-fold; range,
      1.55-2.91), and CD25(+) cells (6.5-fold; range, 4.98-8.13) compared with
      asymptomatic controls. The second group (31 of 77) had nonspecific microscopic
      inflammation and on immunohistology showed similar increases in lymphocyte
      populations (not significant vs. the uninflamed group) as well as increased
      numbers of neutrophil leukocytes and mast cells (P < 0.0001 vs. controls and the
      uninflamed group). The third group (8 of 77) fulfilled histologic and
      immunohistologic criteria for classic lymphocytic colitis. CONCLUSIONS:
      Examination of colonoscopic biopsy specimens from patients meeting the Rome
      criteria for a clinical diagnosis of irritable bowel syndrome showed subgroups
      with normal and abnormal conventional histology. All groups showed increased
      numbers of activated immunocompetent cells in the intestinal mucosa on
      quantitative immunohistology, implicating the mucosal immune system in
      pathogenesis.

PMID- 12055585
TI  - Diet and colorectal cancer: an investigation of the lectin/galactose hypothesis.
AB  - BACKGROUND & AIMS: Mucosal expression of terminal unsubstituted galactose is
      increased in colon cancer and precancer and allows interaction with mitogenic
      galactose-binding lectins of dietary or microbial origin. This study tests the
      hypothesis that galactose, which is variably plentiful in fruit and vegetable but
      not cereal fibers, might prevent cancer by binding and inhibiting such lectins.
      METHODS: Colorectal cancer cases (512) and controls (512) were matched for age,
      sex, primary care practitioner, and postal code. A 160-item food-frequency
      questionnaire was used to estimate their usual pre-illness (6 months previous)
      diet, aspirin intake, and exercise. RESULTS: Neither cereal fiber nor fruit and
      vegetable fiber were protective when assessed by univariate analysis, whereas
      dietary fiber galactose content showed a dose-related protective effect (odds
      ratio [OR] highest quartile/lowest quartile, 0.67; confidence interval [CI], 0.47
      0.95) that remained protective when adjusted for energy, red meat, alcohol,
      calcium, protein and fat intake, regular aspirin usage, and exercise. Intake of
      nonlegume green vegetables, assessed because of the high lectin content of
      legumes, was also protective (OR, 0.54; CI, 0.35-0.81), but this was not
      independent of galactose. Protective effects of exercise and regular daily
      aspirin consumption and harmful effects of high energy consumption and high red
      meat intake were confirmed. CONCLUSIONS: The protective effect of fruit and
      vegetable fibers may be related to their galactose content. This provides further
      evidence that the association between diet and colon cancer is mediated via
      specific food components and may explain the discrepant results of studies
      addressing the protective effects of fiber.

PMID- 12055586
TI  - Lactose malabsorption and intolerance and peak bone mass.
AB  - BACKGROUND & AIMS: Lactose malabsorption per se is not associated with
      alterations of bone mineral density (BMD) or calcium intake, but when intolerance
      symptoms are present a lower calcium intake and reduction of BMD values are
      evident. The purpose of this study was to evaluate whether lactose intolerance
      interferes with the achievement of an adequate peak bone mass in young adults.
      METHODS: Of 103 enrolled healthy subjects, 55 proved to be lactose malabsorbers
      with H(2) breath test after lactose administration, and 29 of them experienced
      intolerance symptoms (diarrhea, abdominal pain, bloating, flatulence). Lumbar and
      femoral BMD by dual-energy X-ray absorptiometry was measured, and calcium intake
      and biochemical indices of bone and mineral metabolism were evaluated. RESULTS:
      Lumbar and femoral BMD, calcium intake, and mineral metabolism did not differ
      between malabsorbers and absorbers, although among malabsorbers, intolerant
      subjects showed significant alterations of all these parameters in comparison
      with tolerant subjects. A strict correlation was evident between BMD values and
      both severity of symptoms and calcium intake and between calcium intake and
      severity of symptoms. CONCLUSIONS: Lactose intolerance prevents the achievement
      of an adequate peak bone mass and may, therefore, predispose to severe
      osteoporosis.

PMID- 12055587
TI  - Prognostic significance of elevated cyclooxygenase 2 expression in patients with
      adenocarcinoma of the esophagus.
AB  - BACKGROUND & AIMS: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is
      associated with a reduced risk of cancer in the digestive tract. Cyclooxygenase
      (COX) is the best-known target of NSAIDs, and expression of the COX-2 isoform is
      elevated in esophageal carcinomas but its clinical significance remains unclear.
      We examined COX-2 expression in esophageal adenocarcinomas and its relation to
      clinicopathologic parameters. METHODS: Tumor sections from 145 consecutive
      patients undergoing intentionally curative surgery for an adenocarcinoma arising
      from a Barrett's esophagus were immunohistochemically stained using a COX-2
      specific anti-human monoclonal antibody. The specimens were scored based on the
      intensity and extent of COX-2 immunopositivity. RESULTS: COX-2 immunoreactivity
      was negative to weak in 21% (COX-2 low) and moderate to strong in 79% (COX-2
      high) of the carcinomas. Patients with high COX-2 expression were more likely to
      develop distant metastases (P = 0.02) and local recurrences (P = 0.05), and
      survival was significantly reduced (P = 0.002, log-rank test) among patients with
      high COX-2 expression when compared with the COX-2 low group. Five-year survival
      rates were 35% (95% confidence interval [CI], 23-47) and 72% (95% CI, 53-90) in
      COX-2 high and COX-2 low categories, respectively. Furthermore, expression of COX
      2 was recognized as an independent prognostic factor by multivariate analysis
      (relative risk, 3.5; 95% CI, 1.6-7.9). CONCLUSIONS: Elevated expression of COX-2
      protein is associated with significantly reduced survival of patients undergoing
      surgery for esophageal adenocarcinoma. These findings support the effort to
      initiate clinical studies to investigate the effect of COX-2 inhibitors as a
      novel (adjuvant) chemotherapeutic modality for the treatment of adenocarcinoma
      arising from Barrett's esophagus.

PMID- 12055588
TI  - Mortality and causes of death in Crohn's disease: follow-up of a population-based
      cohort in Copenhagen County, Denmark.
AB  - BACKGROUND & AIMS: A population-based cohort comprising 374 patients with Crohn's
      disease diagnosed in Copenhagen County between 1962 and 1987 was observed until
      1997 for mortality and causes of death. METHODS: Observed deaths were compared
      with expected deaths calculated by using individually computed person-years at
      risk and 1995 rates for Copenhagen County. Cumulative survival curves were
      calculated. RESULTS: A total of 84 deaths occurred vs. 67 expected (standardized
      mortality ratio [SMR], 1.3; 95% confidence interval [CI], 1.01-1.56): 45 women
      vs. 31.8 expected (SMR, 1.4; 95% CI, 1.03-1.89) and 39 men vs. 35.2 expected
      (SMR, 1.1; 95% CI, 0.79-1.51). An excess mortality was observed among women
      observed for 21-25 years after diagnosis. Among women aged <50 years at
      diagnosis, 25 deaths were observed vs. 7.3 expected (SMR, 3.42; 95% CI, 2.21
      5.04). Fourteen (31%) of the observed deaths among women and 8 (21%) among men
      had a certain or possible connection to Crohn's disease. Among causes of death
      unrelated to Crohn's disease, an overrepresentation of gastrointestinal diseases,
      infections, and diseases of the urinary organs was observed. CONCLUSIONS: An
      increased mortality was observed late in the disease course that was most
      pronounced among women younger than 50 years at diagnosis and was attributed to
      death associated with severe Crohn's disease.

PMID- 12055589
TI  - Occult lymph node metastases as a predictor of tumor relapse in patients with
      node-negative esophageal carcinoma.
AB  - BACKGROUND & AIMS: Esophageal carcinoma is an aggressive disease with a very poor
      prognosis. Early tumor relapse after surgical resection in patients with node
      negative esophageal carcinoma suggests that occult metastases may have been
      missed at the original pathologic examination. The aim of this study was to
      determine the prevalence of immunohistochemically detected occult lymph node
      microscopic metastases in patients with pathologic N0 esophageal carcinoma and
      the impact of these occult metastases on relapse-free survival. METHODS: All
      patients (n = 124) with pathologic N0 esophageal carcinoma undergoing resection
      at our institution between January, 1994, and October, 1998, constituted the
      study population. Esophagectomy specimens were reevaluated by
      immunohistochemistry (monoclonal antibody against cytokeratin AE1/AE3). Clinical
      and pathologic features were summarized, and patient relapse-free survival was
      estimated. RESULTS: Among the total of 124 patients, occult lymph node
      microscopic metastases were identified by immunohistochemistry in 14 patients
      (11%) (T1 mucosa, 4%; T1 submucosa, 6%; T2, 22%; and T3, 14%). Patients were
      followed for a median of 3.2 years. Relapse-free survival was not significantly
      associated with the presence of occult lymph node microscopic metastases as
      detected by immunohistochemistry (P = 0.12). Advanced T stage (T3; P < 0.001) and
      lymphovascular invasion (P < 0.001) were found to be associated with tumor
      relapse. CONCLUSIONS: In the present study, occult lymph node microscopic
      metastases in pathologic N0 esophageal carcinoma patients were less frequent than
      previously reported. T stage and lymphovascular invasion were significantly
      associated with relapse-free survival, although a significant association with
      occult lymph node metastases was not detected.

PMID- 12055590
TI  - Diabetes increases the risk of acute hepatic failure.
AB  - BACKGROUND & AIMS: It is unclear whether patients with diabetes are at an
      increased risk of developing acute liver failure (ALF). We performed a large
      cohort study to examine the occurrence of ALF by using the databases of the
      Department of Veterans Affairs. METHODS: We identified all patients with a
      hospital discharge diagnosis of diabetes (ICD-9 codes: 250 [1-9][0-4]) from 1985
      to 1990 and randomly assigned patients without diabetes for comparison (3:1
      ratio). We excluded patients with concomitant liver disease as far back as 1980.
      After excluding the first year of follow-up, the remaining patients were observed
      through 2000 for the occurrence of ALF (ICD-9 570). The cumulative risk and the
      relative risk of ALF were determined by Kaplan-Meier and Cox Proportional Hazard
      survival analysis, respectively. RESULTS: We included 173,643 patients with
      diabetes and 650,620 patients without diabetes. Patients with diabetes were
      significantly older (62 vs. 54 years) and were less likely to be white (28% vs.
      24%). The cumulative risk of ALF was significantly higher among patients with
      diabetes (incidence rate, 2.31 per 10,000 vs. 1.44 per 10,000 person-years; P <
      0.0001). In the Cox proportional hazard model, diabetes was associated with a
      relative risk of 1.44 (95% CI, 1.26-1.63; P < 0.0001) for ALF while controlling
      for comorbidity index, age, sex, ethnicity, and period of service. This risk
      remained significantly increased after excluding patients with liver disease or
      viral hepatitis recorded during follow-up or those with ALF recorded after the
      introduction of troglitazone (relative risk = 1.40; P < 0.0001). CONCLUSIONS:
      Diabetes increases the risk of ALF. The increase in ALF is independent of
      recognized underlying chronic liver disease or viral hepatitis.

PMID- 12055591
TI  - Regulation of mucosal immune responses by recombinant interleukin 10 produced by
      intestinal epithelial cells in mice.
AB  - BACKGROUND & AIMS: Interleukin (IL)-10 is a cytokine with anti-inflammatory
      properties. The aim of this study was to explore the effect of a site-specific
      delivery of IL-10 on intestinal immune responses. METHODS: Transgenic mice were
      created in which IL-10 is expressed by the intestinal epithelial cells. RESULTS:
      Transgenic mice showed a marked increase in the number of intraepithelial
      lymphocytes in the small intestine. Mucosal lymphocytes of transgenic animals
      produced fewer T helper type 1 cytokines than wild-type lymphocytes. By contrast,
      the production of transforming growth factor beta was increased. Moreover, the
      epithelial layer in transgenic mice was significantly enriched for CD4(+)CD25(+)
      T cells. Furthermore, transgenic mice had increased numbers of immunoglobulin A
      producing B cells in the small intestine. These effects were local because
      splenic lymphocytes were not affected. Studies in models of inflammatory bowel
      disease showed that transgenic IL-10 was able to attenuate the acute colitis
      induced by dextran sodium sulfate administration or by adoptive transfer of
      CD4(+)CD45RB(high) splenocytes, with a modest effect on the chronic intestinal
      inflammation arising spontaneously in IL-10(-/-) mice. CONCLUSIONS: These
      observations provide evidence for an in vivo lymphoepithelial cross talk, by
      which cytokines locally produced by epithelial cells can regulate immune
      responses in the intestine without systemic modifications.

PMID- 12055592
TI  - Differential effects of streptozotocin-induced diabetes on expression of hepatic
      ABC-transporters in rats.
AB  - BACKGROUND & AIMS: Diabetes mellitus is associated with changes in bile
      formation. The aim of our study was to investigate the molecular basis for these
      changes in rats with experimentally induced diabetes. METHODS: Expression of bile
      canalicular transporters was studied by reverse-transcription polymerase chain
      reaction, immunoblotting, and immunohistochemistry in control, streptozotocin
      diabetic, and insulin-treated diabetic rats. Bile formation was studied under
      basal conditions and during stepwise increasing intravenous infusion of
      taurocholate to determine bile salt secretory rate maximum (SRm). RESULTS: In
      diabetic rats, hepatic gene and protein expression of the multidrug resistance P
      glycoprotein type 2 (Mdr2) were increased by 105% and 530%, respectively,
      associated with increased biliary phospholipid output (+520%) and
      phospholipid/bile salt ratio (+77%). Protein levels of the canalicular bile salt
      export pump (Bsep) were unchanged in diabetic rats, but basal biliary bile salt
      output and the SRm of taurocholate were increased by 260% and 130%, respectively,
      compared with controls. Alterations in transporter expression and bile formation
      were partly reversed by insulin administration. The bile salt SRm was strongly
      correlated with biliary phospholipid concentration (P < 0.001, R = 0.82).
      CONCLUSIONS: Induction of Mdr2 expression and biliary phospholipid secretion,
      rather than Bsep expression, appears to be responsible for the enhanced capacity
      of biliary bile salt secretion in experimentally induced diabetes.

PMID- 12055594
TI  - Role of shear stress in aortic eNOS up-regulation in rats with biliary cirrhosis.
AB  - BACKGROUND & AIMS: In rats with portal vein stenosis, the initial cause of aortic
      nitric oxide (NO) overproduction might be overactivation of endothelial NO
      synthase (eNOS) related to increased shear stress. Cardiac output is higher in
      cirrhosis than in extrahepatic portal hypertension. The aims of this study were
      to evaluate the role of shear stress, vascular endothelial growth factor (VEGF),
      and cytokines in aortic eNOS up-regulation in rats with biliary cirrhosis and to
      compare these results with those in rats with portal vein stenosis. METHODS: NOS
      activities, NOS protein, heat shock protein (Hsp) 90, and VEGF expressions were
      studied in rat aortas. Propranolol was administered to rats with cirrhosis to
      reduce cardiac output and thus shear stress. RESULTS: In cirrhotic rats, the
      aortic eNOS protein was 3.0 and 1.7 times higher than in control and portal vein
      stenosed rats, respectively. In cirrhotic rats, the Hsp90 content was 3.2 and 2.2
      times higher than in control and portal vein-stenosed rats, respectively.
      Propranolol decreased NOS activity by 47% and eNOS and Hsp90 expression by 75%
      and 72%, respectively. Aortic VEGF expression was decreased in cirrhotic rats.
      VEGF-induced stimulation of NOS activity was greater in aortas from control rats
      than in aortas from portal vein-stenosed or cirrhotic rat aortas. eNOS expression
      was up-regulated after VEGF incubation. After lipopolysaccharide administration,
      eNOS expression did not change in portal vein-stenosed or cirrhotic rats.
      CONCLUSIONS: This study shows that in aortas from rats with biliary cirrhosis,
      systemic vasodilation depends mainly on eNOS up-regulation related to shear
      stress.

PMID- 12055593
TI  - Abnormal organogenesis of Peyer's patches in mice deficient for NF-kappaB1, NF
      kappaB2, and Bcl-3.
AB  - BACKGROUND & AIMS: Nuclear factor (NF) kappaB1, NF-kappaB2, and Bcl-3 encode for
      proteins of the NF-kappaB/Rel/IkappaB families, known as regulators of innate and
      adoptive immune responses. Targeted disruption of these genes showed essential
      roles in lymphoid organ development and organization. METHODS: NF-kappaB1-, NF
      kappaB2-, and Bcl-3-deficient mouse lines were established, and their role in
      organogenesis of Peyer's patches (PP) was investigated. RESULTS: Macroscopic
      inspection showed a reduced number and size of PP in Bcl-3(-/-) and NF-kappaB1(-/
      ) mice but failed to detect PP in NF-kappaB2(-/-) mice. Whole-mount in situ
      hybridization revealed the presence of interleukin-7 receptor-alpha spots in NF
      kappaB2(-/-) mice, indicating no defect in PP organogenesis of NF-kappaB2(-/-)
      mice in principle. Immunostaining shows that residual lymphocytes mainly consist
      of T cells. B cells are substantially reduced and are accumulated as terminal
      extravasations. Organized follicular structures and follicular dendritic cell
      networks fail to form, and myeloid, but not lymphoid, dendritic cells are
      obviously reduced. Expression of the chemokines macrophage inflammatory protein
      3alpha, B-lymphocyte chemoattractant, and thymus-expressed chemokine is impaired
      in epithelial cells and in the subendothelial dome area that is not well defined.
      A similar but less severe phenotype is seen in Bcl-3(-/-) mice, which also do not
      develop germinal centers. In contrast, in NF-kappaB1(-/-) mice, T-cell numbers
      are visibly reduced, and no alteration could be observed in the B-cell and
      dendritic-cell populations. CONCLUSIONS: These data show that all 3 genes are
      crucial for PP development but contribute differently to PP organogenesis.

PMID- 12055595
TI  - Molecular misreading of the ubiquitin B gene and hepatic mallory body formation.
AB  - BACKGROUND & AIMS: Molecular misreading of the ubiquitin B gene has been
      documented in the cerebral cortex of patients with Alzheimer's disease and Down
      syndrome. This novel process consists of the unfaithful conversion of genomic
      information into aberrant transcripts and its subsequent translation into +1
      proteins. METHODS: Because Mallory bodies (MBs) also contain ubiquitinated
      proteins, we stained 11 autopsied and 6 biopsied MB-containing livers from
      patients with steatohepatitis with an antibody to ubiquitin(+1) to look for the
      presence of mutant (ubiquitin(+1)) protein. Antibodies to wild-type ubiquitin
      were used to document the presence of MBs in all cases. RESULTS: Ubiquitin(+1)
      immunoreactivity was detected in all MB-containing livers with steatohepatitis;
      no ubiquitin(+1) immunoreactivity was found in 13 MB-free liver controls. A
      subpopulation (about one third of the MBs) of the MB-containing hepatocytes in
      autopsied livers showed ubiquitin(+1) immunoreactivity (i.e., ubiquitin and
      ubiquitin(+1) colocalized in MBs). MB-containing liver biopsy specimens showed
      colocalization of ubiquitin and ubiquitin(+1) in every MB. Western blot analysis
      showed an ubiquitin(+1) band of 11 kilodaltons. Molecular misreading of the
      ubiquitin B gene (DeltaGU) was shown in one of the livers, which contained
      numerous MBs using an expression cloning strategy. CONCLUSIONS: The results
      showed that molecular misreading of the ubiquitin B gene occurred in hepatocytes
      in virtually all of the MB-containing livers tested. Ubiquitin(+1) protein was
      only found within the MBs and therefore may act by interfering with the
      degradation of the MBs because ubiquitin(+1) may inhibit proteolytic function of
      the proteasome.

PMID- 12055596
TI  - Molecular and functional observations on the donor intestinal muscularis during
      human small bowel transplantation.
AB  - BACKGROUND & AIMS: Ischemia-reperfusion injury or intestinal manipulation evokes
      an inflammatory response within the intestinal muscularis that is associated with
      intestinal dysmotility. We hypothesize that human small intestinal
      transplantation induces an analogous response. METHODS: Human intestinal graft
      specimens were obtained during transplantation and compared with specimens
      removed early during elective bowel resections. Inflammatory gene expression was
      quantified by real-time reverse-transcription polymerase chain reaction.
      Histochemistry and immunohistochemistry were used to characterize leukocyte
      infiltration and macrophage activation. In vitro circular muscle contractility
      and intracellular electric neuromuscular transmission in response to electric
      field stimulation (EFS) were measured. RESULTS: Messenger RNA (mRNA) values were
      significantly elevated before reperfusion and further increased during
      reperfusion (4 hour reperfusion: interleukin [IL]-6, 311-fold; monocyte
      chemoattractant protein [MCP-1, 122-fold; IL-8, 338-fold; epithelial neutrophil
      activating peptide-78 [ENA-78], 56-fold; intercellular adhesion molecule-1 [ICAM
      1], 9-fold; and cyclooxygenase-2 [COX2], 37-fold) over elective specimens.
      Neutrophils and monocytes extravasated in increased numbers in whole mounts
      before and after reperfusion over the elective specimens. Activated resident
      macrophages were identified as a major source of inflammatory mediators. Muscle
      contractions and neuromuscular transmission were markedly attenuated in the
      grafts. CONCLUSIONS: The data suggest that manipulation during organ harvesting
      initiates a functionally relevant molecular and cellular inflammatory response
      within the graft muscularis that is potentiated during the reperfusion period.
      Significant mechanical and neuromuscular functional alterations occurred during
      the transplant process.

PMID- 12055597
TI  - Transgenic overexpression of amphiregulin induces a mitogenic response
      selectively in pancreatic duct cells.
AB  - BACKGROUND & AIMS: The epidermal growth factor (EGF) receptor family and the
      corresponding ligands are frequently overexpressed in pancreatic cancer. To
      compare the biological effects of transforming growth factor (TGF)-alpha and
      amphiregulin (AR) on growth and differentiation of the exocrine pancreas, we have
      generated transgenic mice overexpressing AR under control of the elastase
      promoter. METHODS: Two independently generated transgenic mouse lines overexpress
      50-, 43-, 28-, 26-, and 16-kilodalton AR forms in the pancreas. RESULTS:
      Morphologic and immunohistochemical examinations suggest that small intralobular
      duct and centro-acinar cells proliferate in response to AR in these mice. AR
      transgenic mice display increased Ras, Erk1/2, cyclin D/CDK4, and cyclin E/CDK2
      activity and G1/S progression in pancreatic duct cells. In contrast to TGF-alpha
      transgenic mice, AR neither induced tubular complex formation nor elicited a
      strong fibrogenic response. AR induced a slight induction of ErbB2 on duct cells,
      whereas TGF-alpha resulted in overexpression of the EGF receptor in cells within
      tubular complexes. Furthermore, AR and TGF-alpha displayed different effects on
      differentiation of isolated acini in vitro comparable to the situation in vivo.
      CONCLUSIONS: These data suggest that AR induces a mitogenic response selectively
      in small duct cells through activation of Ras, CDK2, and CDK4, respectively. The
      closely related EGF receptor ligands, AR and TGF-alpha, display different
      biological effects when overexpressed in the exocrine pancreas in vivo.

PMID- 12055598
TI  - COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti
      inflammatory drug enteropathy in mice.
AB  - BACKGROUND & AIMS: The pathogenesis of nonsteroidal anti-inflammatory drug
      induced enteropathy is controversial, but it is thought that cyclooxygenase-1
      (COX-1) inhibition is of pivotal importance. We compared small intestinal
      function and morphology in untreated wild-type, COX-1- and COX-2-deficient mice
      and the effect of indomethacin, selective COX-1 (SC-560), and COX-2 (celecoxib)
      inhibition. METHODS: Intestinal permeability ((51)CrEDTA), inflammation (fecal
      granulocyte marker protein), prostaglandin E(2) (PGE(2)) levels, and macroscopic
      and microscopic appearances were assessed at baseline and after the drugs.
      RESULTS: COX-1(-/-) animals were normal except for a 97% decrease in intestinal
      PGE(2) levels. COX-1(+/+) and COX-1(-/-) animals reacted in a similar way to
      indomethacin. However, celecoxib, having caused no damage in COX-1(+/+) animals,
      caused small bowel ulcers in COX-1(-/-) animals. Selective inhibition of COX-1
      decreased intestinal PGE(2) levels in COX-2(+/+) and COX-2(-/-) animals by 95%
      97%, but caused only small bowel ulcers in the latter group. Dual inhibition of
      COX-1 and COX-2 in wild-type animals resulted in similar small bowel damage.
      Between 40% and 50% of untreated COX-2(-/-) animals had increased intestinal
      permeability and inflammation. Some had ileal ulcers that were distinctively
      different from indomethacin-induced ulcers. Furthermore, long-term celecoxib
      administration in wild-type animals was associated with similar damage as in the
      COX-2(-/-) mice. CONCLUSIONS: COX-1 deficiency or inhibition and short-term COX-2
      inhibition are compatible with normal small intestinal integrity. Dual inhibition
      of the COX enzymes leads to damage similar to that seen with indomethacin. Long
      term COX-2 deficiency or inhibition is associated with significant intestinal
      pathology despite normal intestinal PGE(2) levels, suggesting a role for COX-2 in
      the maintenance of small intestinal integrity in the mouse.

PMID- 12055600
TI  - Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat
      pancreatic acinar cells.
AB  - BACKGROUND & AIMS: The mechanism by which cholelithiasis increases the risk of
      acute pancreatitis remains obscure. Because bile acids can enter the pancreas
      either by luminal diffusion or by interstitial leakage during gallstone impaction
      and pancreatitis is associated with impaired Ca(2+) signaling, we examined the
      effect of bile acids on pancreatic acinar cell signaling and the associated
      intracellular events. METHODS: Rat pancreatic acinar cells were isolated by
      collagenase digestion and the effects of bile acids on [Ca(2+)](i) signaling,
      cell survival, inflammatory signals, and the molecular and functional expressions
      of bile uptake transporters were analyzed. RESULTS: Bile acids specifically
      inhibited the sarco/endoplasmic reticulum Ca(2+) ATPase pump to chronically
      deplete part of the Ca(2+) stored in the endoplasmic reticulum. This in turn led
      to the activation of capacitative Ca(2+) entry and a chronic [Ca(2+)](i) load.
      The increase in [Ca(2+)](i) and Ca(2+) load activated the inflammation-associated
      signals of c-Jun amino-terminal kinases and NF-kappaB and led to cell death,
      which was inhibited by buffering [Ca(2+)](i) with 1,2-bis(2-aminophenoxy)ethane
      N,N,N,N'-tetraacetic acid. A comprehensive molecular analysis of bile acid
      transporters revealed that pancreatic acinar cells express the bile uptake
      transporters Na(+)-taurocholate co-transporting polypeptide and organic anion
      transporting polypeptide in the luminal and basolateral membranes, respectively.
      Bile acid uptake into acinar cells was in part Na(+)-dependent and in part Na(+)
      independent, suggesting that both transporters contribute to bile acid influx
      into acinar cells. CONCLUSIONS: These results suggest that bile acids can be
      transported into pancreatic acinar cells through specific membrane transporters
      and induce cell death by impairing cellular Ca(2+) signaling.

PMID- 12055599
TI  - Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate
      cell activation in vivo and in vitro.
AB  - BACKGROUND & AIMS: The ligand-dependent transcription factor peroxisome
      proliferator-activated receptor gamma (PPARgamma) is expressed in hepatic
      stellate cells (HSC), and its transcriptional activity is reduced during cell
      transdifferentiation in culture. PPARgamma transcriptional activation decreases
      platelet-derived growth factor-induced proliferation and inhibits alpha-smooth
      muscle actin expression in cultured HSC. The aim of our study was to evaluate
      whether oral administration of synthetic PPARgamma ligands, thiazolidinediones
      (TZD), might affect collagen deposition in animal models of liver fibrosis.
      METHODS: The effect of 2 TZD (pioglitazone or rosiglitazone) was tested on liver
      fibrosis induced in rats by either toxin administration (dimethylnitrosamine or
      carbon tetrachloride) or bile duct ligation. In vivo PPARgamma activation was
      evaluated by gel shift assay using nuclear extracts from HSC isolated from
      control and treated rats. RESULTS: Oral administration of TZD reduced
      extracellular matrix deposition and HSC activation in both toxic and cholestatic
      models of liver fibrosis. PPARgamma-specific DNA binding was significantly
      impaired in nuclear extracts of HSC isolated from fibrotic rats compared with HSC
      from control rats. TZD administration restored PPARgamma DNA binding in HSC
      nuclei. In vitro, TZD-induced PPARgamma activation inhibited collagen and
      fibronectin synthesis induced by transforming growth factor (TGF)-beta1 in human
      HSC, as measured by enzyme-linked immunosorbent assay and Northen blotting. TZD
      also reduced the TGF-beta1-induced activity of a 3.5-kilobase procollagen type I
      promoter transfected in human HSC. CONCLUSIONS: These findings indicate that
      PPARgamma activation in HSC retards fibrosis in vivo and suggest the use of TZD
      for the treatment of liver fibrosis.

PMID- 12055601
TI  - Human organic anion transporting polypeptide 8 promoter is transactivated by the
      farnesoid X receptor/bile acid receptor.
AB  - BACKGROUND & AIMS: OATP8 (gene symbol: SLC21A8) is a multispecific uptake system
      for organic anions, xenobiotics, and peptides expressed at the basolateral
      (sinusoidal) membrane of human hepatocytes. We investigated whether OATP8 gene
      expression is regulated by the nuclear receptors farnesoid X receptor/bile acid
      receptor (FXR/BAR; NR1H4), pregnane X receptor (PXR), or liver X receptor (LXR).
      METHODS: OATP8 promoter function was studied in reporter assays. OATP8 expression
      in cells was quantitated by real-time polymerase chain reaction. RESULTS: The
      bile acid chenodeoxycholic acid (CDCA), a ligand of FXR/BAR, but not clotrimazole
      or 25-hydroxycholesterol, ligands of PXR or LXR, respectively, induced OATP8
      promoter activity. An inverted hexanucleotide repeat motif (IR-1 element) in the
      promoter sequence was shown by electrophoretic mobility shift assays to bind the
      FXR (9-cis-retinoic acid receptor [RXRalpha]) heterodimer. Targeted mutagenesis
      of the IR-1 element abolished inducibility of the OATP8 promoter by CDCA,
      confirming its role as a bile acid response element. CDCA treatment increased
      OATP8 messenger RNA levels in human hepatoma cells, suggesting a physiologic role
      for FXR-mediated OATP8 gene regulation. CONCLUSIONS: OATP8 gene expression is
      regulated by bile acids via FXR/BAR. Induction of OATP8 could serve to maintain
      hepatic extraction of xenobiotics and peptides in conditions of increased
      intracellular bile acids.

PMID- 12055602
TI  - Norwalk virus binds to histo-blood group antigens present on gastroduodenal
      epithelial cells of secretor individuals.
AB  - BACKGROUND & AIMS: Norwalk Virus (NV) is a member of the Caliciviridae family,
      which causes acute epidemic gastroenteritis in humans of all ages and its
      cellular receptors have not yet been characterized. Another calicivirus, Rabbit
      Hemorrhagic Disease Virus, attaches to H type 2 histo-blood group oligosaccharide
      present on rabbit epithelial cells. Our aim was to test if, by analogy,
      recombinant NV-like particles (rNV VLPs) use carbohydrates present on human
      gastroduodenal epithelial cells as ligands. METHODS: Attachment of rNV VLPs was
      tested on tissue sections of the gastroduodenal junction and on saliva from
      individuals of known ABO, Lewis, and secretor phenotypes. It was also tested on
      human Caco-2 cells and on animal cell lines transfected with glycosyltransferases
      complementary DNA (cDNA). Competition experiments were performed with synthetic
      oligosaccharides and anticarbohydrate antibodies. Internalization was monitored
      by confocal microscopy. RESULTS: Attachment of rNV VLPs to surface epithelial
      cells of the gastroduodenal junction as well as to saliva was detected, yet only
      from secretor donors. It was abolished by alpha1,2fucosidase treatment, and by
      competition with the H types 1 and 3 trisaccharides or with anti-H type 1 and
      anti-H types (3/4) antibodies. Transfection of CHO and TS/A cells with an
      alpha1,2fucosyltransferase cDNA allowed attachment of VLPs. These transfectants
      as well as differentiated Caco-2 cells expressing H type 1 structures
      internalized the bound particles. CONCLUSIONS: rNV VLPs use H type 1 and/or H
      types (3/4) as ligands on gastroduodenal epithelial cells of secretor
      individuals.

PMID- 12055603
TI  - Production of nerve growth factor by mouse hepatocellular carcinoma cells and
      expression of TrkA in tumor-associated arteries in mice.
AB  - BACKGROUND & AIMS: Nerve growth factor (NGF) has been suggested to play a role in
      cancer progression. We found that NGF is specifically elevated in mouse
      hepatocellular carcinomas (HCCs) by cDNA array analysis. The present study aimed
      to elucidate expression of NGF and its receptors during hepatocarcinogenesis and
      under other conditions. METHODS: Expression of NGF, TrkA, and p75NTR was
      investigated in HCCs developing and regenerating livers, and primary hepatocyte
      cultures in B6C3F(1) mice by reverse-transcription polymerase chain reaction,
      Northern blotting, and/or immunohistochemistry. The biological activity of NGF
      produced by the HCC cells was studied by using PC12 cells. Nerve fibers in
      hepatic tumors were immunohistochemically examined. RESULTS: Although NGF was
      negative in adult and developing livers, it was markedly elevated in focal
      hepatocytic lesions from early stages of carcinogenesis. Appreciable levels were
      also detected in regenerating livers and hepatocytes in culture. The conditioned
      medium of HCC cells caused PC12 neurite outgrowth, but this was reduced on
      pretreatment of the conditioned medium with an anti-NGF antibody or NGF antisense
      expression in HCC cells. Although neither TrkA nor p75NTR was detectable in
      either HCC or normal hepatic cells, TrkA was shown in the walls of tumor
      associated arteries that contain abundant nerve fibers. CONCLUSIONS: NGF is
      expressed by hepatocytes during carcinogenesis, regeneration, and primary culture
      but may have cells other than hepatocytes as the target. TrkA expression and the
      abundance of nerve fibers in the walls of tumor-associated arteries suggest a
      possible role for NGF in angiogenesis.

PMID- 12055604
TI  - Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation.
AB  - BACKGROUND & AIMS: Bacterial wall products play an important role in the
      activation of immune and nonimmune cells of the intestinal mucosa. Toll-like
      receptors (TLRs) TLR2 and TLR4 have been identified as signaling receptors
      activated by bacterial wall components. METHODS: Expression of TLRs in human
      intestinal mucosa obtained by endoscopy and surgery was analyzed by
      immunohistochemistry. Intestinal macrophages were isolated by immunomagnetic
      beads armed with a CD33 antibody. Reverse-transcription polymerase chain reaction
      was performed for TLR1-5. Results were confirmed by Northern blot and flow
      cytometry. Interleukin-1beta messenger RNA (mRNA) was quantified by a polymerase
      chain reaction-enzyme-linked immunosorbent assay-kit. RESULTS:
      Immunohistochemistry revealed a significant increase in the TLR2 and TLR4 antigen
      expression on submucosal cells in inflamed intestinal mucosa compared with non
      inflamed mucosa. TLR expression was localized in intestinal macrophages by double
      labeling techniques. No TLR-polymerase chain reaction product could be obtained
      with mRNA from CD33-positive macrophages from normal mucosa. We observed an
      induction of mRNA for TLR2, TLR4, and TLR5 in inflammation-associated
      macrophages. TLR1 and TLR3 were only detectable in blood monocytes. Monocytes
      reacted to lipopolysaccharide stimulation with a 3-fold and in vitro
      differentiated macrophages with a 16-fold increase of cellular interleukin-1beta
      mRNA. Macrophages from normal mucosa did not respond to lipopolysaccharide
      showing the functional relevance of TLR expression. CONCLUSIONS: This study shows
      the inflammation-dependent induction of TLR2 and TLR4 expression in intestinal
      macrophages. The absence of TLRs abolishes the reactivity of mucosal macrophages
      to bacterial wall products. Presence of TLRs may thereby contribute to the
      inflammatory process.

PMID- 12055605
TI  - Critical role of interleukin 5 and eosinophils in concanavalin A-induced
      hepatitis in mice.
AB  - BACKGROUND & AIMS: Eosinophils are observed in several liver diseases, but their
      contribution in the pathogenesis of these disorders remains poorly investigated.
      Concanavalin A (Con A)-induced hepatitis is an experimental model of immune
      mediated liver injury in which natural killer T (NKT) cells play a critical role
      through the production of interleukin (IL)-4 and the expression of Fas ligand
      (FasL). Because activated NKT cells also produce IL-5, a critical cytokine for
      eosinophil maturation and function, the role of IL-5 was investigated in this
      model. METHODS: IL-5-deficient mice, eosinophil depletion in wild-type (WT) mice,
      and NKT cell transfer from WT- or IL-5-deficient mice into NKT cell-deficient
      mice were used to assess the role of IL-5 and eosinophils. RESULTS: Liver
      eosinophil infiltrate and IL-5 production were observed after Con A challenge.
      Liver injury was dramatically reduced in IL-5-deficient or eosinophil-depleted
      mice. In addition, residual hepatitis observed in Fas-deficient mice was
      abolished after IL-5 neutralization. Finally, we showed that NKT cells
      constituted a critical source of IL-5. Indeed, transfer of WT NKT cells to mice
      lacking NKT cells restored liver injury, whereas transfer of IL-5-deficient NKT
      cells did not. CONCLUSIONS: These observations highlight the pathologic role of
      IL-5 and eosinophils in experimental immune-mediated hepatitis.

PMID- 12055607
TI  - Successful sequential liver and stem cell transplantation for hepatic failure due
      to primary AL amyloidosis.
AB  - We report on a patient with primary AL amyloidosis who presented with progressive
      liver failure secondary to hepatic infiltration in the absence of significant
      extrahepatic involvement. Orthotopic liver transplantation was performed
      successfully. After an uneventful postoperative course, the patient developed
      evidence of significant recurrent amyloidosis requiring treatment. He then
      underwent stem cell transplantation 10 and 14 months after liver transplantation.
      After 28 months of follow-up posttransplantation, the patient continues to do
      well, with no clinical evidence of recurrent disease. This is the first reported
      patient with primary amyloidosis to undergo sequential liver and stem cell
      transplantation leading to resolution of the disease and only the second to
      undergo successful liver transplantation for this disorder.

PMID- 12055606
TI  - Leptin: a pivotal mediator of intestinal inflammation in mice.
AB  - BACKGROUND & AIMS: In addition to acting as a regulator of food intake and energy
      expenditure, leptin can also modulate immune and inflammatory responses. The role
      of leptin in intestinal inflammation is the focus of the present study. METHODS:
      Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type
      (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid
      (TNBS). The severity of colitis was evaluated, and possible mechanisms were
      studied. RESULTS: Leptin directly stimulates intraepithelial lymphocytes (IELs)
      and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice
      exhibited a 72% reduction of colitis severity and spontaneous release of
      proinflammatory cytokines from the colon compared with WT mice. Replacement of
      leptin in ob/ob mice converted disease resistance to susceptibility, indicating
      that leptin deficiency, not obesity, accounts for the resistance to acute DSS
      induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in
      addition to reduced disease severity, ob/ob mice exhibited a significant
      attenuation in intestinal inflammation, accompanied by reduced production of
      cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice
      were reduced in number as well as in their ability to synthesize interferon
      gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated
      as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and
      activator of transcription 3 and induction of cyclooxygenase 2 were absent in the
      colon of DSS-fed ob/ob mice. CONCLUSIONS: These results show that leptin
      represents a functional link between the endocrine and immune systems.

PMID- 12055608
TI  - Evolving pathophysiologic models of functional gastrointestinal disorders.
AB  - In contrast to most other disorders of the digestive system, functional disorders
      of the gut continue to be defined by symptom criteria rather than by biological
      markers. At the same time, animal models of functional gastrointestinal disorders
      in which to test pathophysiologic hypotheses are lacking. The aim of this report
      is to critically review recently proposed conceptual as well as animal models of
      functional gastrointestinal disorders. Converging disease models have been
      proposed that postulate an enhanced responsiveness of neural, immune, or
      neuroimmune circuits in the central nervous system or in the gut to exteroceptive
      (psychosocial) or interoceptive (tissue irritation, inflammation, infection)
      perturbations of the organism's homeostasis. The enhanced responsiveness results
      in dysregulation of gut motility, epithelial function (immune, permeability), and
      visceral hypersensitivity, which in turn produce irritable bowel syndrome
      symptoms. These conceptual models provide plausible mechanisms for irritable
      bowel syndrome symptom generation and are consistent with extensive epidemiologic
      and pathophysiologic data. Several animal models have recently been proposed that
      mimic key features of these conceptual disease models. They fall into models
      triggered by centrally targeted stimuli (neonatal stress, post-traumatic stress
      disorder) or those triggered by peripherally targeted stimuli (infection,
      inflammation). Depending on the timing of the trigger (neonatal vs. adult), the
      changes induced in the animal may be permanent or transient. Future development
      of existing and novel models involves the use of transgenic and knockout animals,
      as well as the demonstration of predictive validity in terms of responsiveness to
      candidate drugs.

PMID- 12055610
TI  - Presentation of the Julius M. Friedenwald Medal to Sidney Cohen, M.D.

PMID- 12055611
TI  - Potential roles for chemokine receptor CCR5 in the pathobiology of hepatitis C
      infection.

PMID- 12055612
TI  - Spreading and focusing of gluten epitopes in celiac disease.

PMID- 12055609
TI  - Alcohol and mitochondria: a dysfunctional relationship.
AB  - Mitochondria are intimately involved in the generation of and defense against
      reactive oxygen species (ROS). Mitochondria are themselves targets of oxidative
      stress and also contribute to mechanisms by which oxidative stress-related
      signals control cell fate. Ethanol promotes oxidative stress, both by increasing
      ROS formation and by decreasing cellular defense mechanisms. These effects of
      ethanol are prominent in the liver, the major site of ethanol metabolism in the
      body. The question remains to what extent this contributes to ethanol-dependent
      tissue damage or the susceptibility of cells to other stressors. In this review,
      we consider how mitochondrial actions of ethanol influence oxidative stress
      management of liver cells. Mitochondrial electron transport constitutes the major
      intracellular source of ROS, and ethanol treatment imposes conditions that
      promote ROS formation by mitochondria, the effects of which may be enhanced by a
      decrease in mitochondrial oxidative stress defenses. A significant target of
      ethanol-related increases in oxidative stress is mitochondrial DNA. Ethanol
      induced damage to mitochondrial DNA, if not adequately repaired, impairs
      mitochondrial function, which further increases oxidative stress in the cell,
      leading to a vicious cycle of accumulating cell damage that is more apparent with
      advancing age. Uncontrolled mitochondrial formation of ROS promotes the
      inappropriate activation of the mitochondrial permeability transition, increasing
      the sensitivity of cells to other pro-apoptotic or damage signals. In combination
      with ethanol-induced defects in mitochondrial function, these alterations may
      promote both apoptotic and necrotic cell death in response to otherwise benign or
      beneficial challenges and contribute to the onset or progression of alcohol
      induced liver diseases.

PMID- 12055613
TI  - Do we need to perform rectal distention tests to diagnose IBS in clinical
      practice?

PMID- 12055614
TI  - A case for an immunological basis for irritable bowel syndrome.

PMID- 12055615
TI  - Parent-child transmission of Helicobacter pylori in the family.

PMID- 12055616
TI  - The c-insertion mutation of the NOD2 gene is associated with fistulizing and
      fibrostenotic phenotypes in Crohn's disease.

PMID- 12055617
TI  - Serum HBV-DNA levels in inactive hepatitis B virus carriers.

PMID- 12055618
TI  - Drink tests in functional dyspepsia.

PMID- 12055619
TI  - Anticoagulation therapy for recent portal vein thrombosis in a patient with liver
      cirrhosis suffering from variceal rebleeding.

PMID- 12055620
TI  - Structural insights into lesion recognition and repair by the bacterial 8
      oxoguanine DNA glycosylase MutM.
AB  - MutM is a bacterial 8-oxoguanine glycosylase responsible for initiating base
      excision repair of oxidized guanine residues in DNA. Here we report five
      different crystal structures of MutM-DNA complexes that represent different steps
      of the repair reaction cascade catalyzed by the protein and also differ in the
      identity of the base opposite the lesion (the 'estranged' base). These structures
      reveal that the MutM active site performs the multiple steps of base-excision and
      3' and 5' nicking with minimal rearrangement of the DNA backbone.

PMID- 12055621
TI  - The structure of VibH represents nonribosomal peptide synthetase condensation,
      cyclization and epimerization domains.
AB  - Nonribosomal peptide synthetases (NRPSs) are large, multidomain enzymes that
      biosynthesize medically important natural products. We report the crystal
      structure of the free-standing NRPS condensation (C) domain VibH, which catalyzes
      amide bond formation in the synthesis of vibriobactin, a Vibrio cholerae
      siderophore. Despite low sequence identity, NRPS condensation enzymes are
      structurally related to chloramphenicol acetyltransferase (CAT) and
      dihydrolipoamide acyltransferases. However, although the latter enzymes are
      homotrimers, VibH is a monomeric pseudodimer. The VibH structure is
      representative of both NRPS condensation and epimerization domains, as well as
      the condensation-variant cyclization domains, which are all expected to be
      monomers. Surprisingly, despite favorable positioning in the active site, a
      universally conserved histidine important in CAT and in other C domains is not
      critical for general base catalysis in VibH.

PMID- 12055622
TI  - The bacterial protein SipA polymerizes G-actin and mimics muscle nebulin.
AB  - SipA is a Salmonella protein delivered into host cells to promote efficient
      bacterial entry, which is essential for pathogenicity. SipA exerts its function
      by binding F-actin, resulting in the stabilization of F-actin and the stimulation
      of the bundling activity of fimbrin. Here we show that under low salt conditions
      where spontaneous nucleation and polymerization of actin do not occur, SipA
      induces extensive polymerization. We have used electron microscopy and a method
      for helical image analysis to visualize the complex of actin with the actin
      binding fragment of SipA. The SipA fragment binds to actin as a tubular molecule
      extending approximately 95 A. The main sites of SipA binding on actin involve
      sequence insertions that are not present in the bacterial homolog of actin, MreB,
      suggesting a mechanism for preventing SipA from interacting with bacterial MreB
      filaments. Remarkably, the pattern of SipA binding, which connects subunits on
      opposite actin strands and explains the stabilization of F-actin, is similar to
      that shown for a fragment of the giant muscle protein nebulin. We suggest that
      SipA is a bacterial structural mimic of muscle nebulin and nebulin-like proteins
      in non-muscle cells that are involved in the regulation of the actin-based
      cytoskeleton.

PMID- 12055623
TI  - Structure of human phosphatidylcholine transfer protein in complex with its
      ligand.
AB  - Phosphatidylcholines (PtdChos) comprise the most common phospholipid class in
      eukaryotic cells. In mammalian cells, these insoluble molecules are transferred
      between membranes by a highly specific phosphatidylcholine transfer protein (PC
      TP) belonging to the steroidogenic acute regulatory protein related transfer
      (START) domain superfamily of hydrophobic ligand-binding proteins. The crystal
      structures of human PC-TP in complex with dilinoleoyl-PtdCho or palmitoyl
      linoleoyl-PtdCho reveal that a single well-ordered PtdCho molecule occupies a
      centrally located tunnel. The positively charged choline headgroup of the lipid
      engages in cation-pi interactions within a cage formed by the faces of three
      aromatic residues. These binding determinants and those for the phosphoryl group
      may be exposed to the lipid headgroup at the membrane-water interface by a
      conformational change involving the amphipathic C-terminal helix and an Omega
      loop. The structures presented here provide a basis for rationalizing the
      specificity of PC-TP for PtdCho and may identify common features used by START
      proteins to bind their hydrophobic ligands.

PMID- 12055624
TI  - Programmed contraction of CD8(+) T cells after infection.
AB  - The extent of infection and rate of pathogen clearance are thought to determine
      both the magnitude of antigen-specific CD8(+) T cell expansion and the ensuing
      contraction to a stable number of memory cells. We show that CD8(+) T cell
      expansion after Listeria monocytogenes infection was primarily dependent on the
      initial infection dose or amount of antigen displayed, and was also influenced by
      the rate of pathogen clearance. However, the onset and kinetics of CD8(+) T cell
      contraction after L. monocytogenes and lymphocytic choriomeningitis virus
      infections were independent of the magnitude of expansion, dose and duration of
      infection or amount of antigen displayed. Thus, major features of antigen
      specific CD8(+) T cell homeostasis, including the contraction phase of an immune
      response, may be programmed early after infection.

PMID- 12055625
TI  - Human epithelial cells trigger dendritic cell mediated allergic inflammation by
      producing TSLP.
AB  - Whether epithelial cells play a role in triggering the immune cascade leading to
      T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that
      human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic
      cells (DCs) and induced production of the T(H)2-attracting chemokines TARC
      (thymus and activation-regulated chemokine; also known as CCL17) and MDC
      (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naive T(H) cells
      to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor
      necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma. TSLP was
      highly expressed by epithelial cells, especially keratinocytes from patients with
      atopic dermatitis. TSLP expression was associated with Langerhans cell migration
      and activation in situ. These findings shed new light on the function of human
      TSLP and the role played by epithelial cells and DCs in initiating allergic
      inflammation.

PMID- 12055626
TI  - T cell immunodominance and maintenance of memory regulated by unexpectedly cross
      reactive pathogens.
AB  - We show here that T cell cross-reactivity between heterologous viruses influences
      the immunodominance of virus-specific CD8(+) T cells by two mechanisms. First, T
      cells specific for cross-reactive epitopes dominate acute responses to viral
      infections; second, within the memory pool, T cells specific for cross-reactive
      epitopes are maintained while those specific for non-cross-reactive epitopes are
      selectively lost. These findings suggest an immunological paradigm in which viral
      infections shape the available T cell repertoire, causing alterations in the
      hierarchies of both the primary and memory CD8(+) T cell responses elicited by
      subsequent viral infections. Thus, immunodominance is a function of the host's
      previous exposure to unrelated pathogens, and this may have an impact on
      protective immunity and immunopathology.

PMID- 12055627
TI  - Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1
      gene induction.
AB  - Type 1 helper T (T(H)1) cells are essential for cellular immunity, but their
      ontogeny, maturation and durability remain poorly understood. By constructing a
      dominant-negative form of T-bet, we were able to determine the role played by
      this lineage-inducing trans-activator in the establishment and maintenance of
      heritable T(H)1 gene expression. Optimal induction of interferon-gamma (IFN
      gamma) expression required genetic interaction between T-bet and its target, the
      homeoprotein Hlx. In fully mature T(H)1 cells, reiteration of IFN-gamma
      expression and stable chromatin remodeling became relatively independent of T-bet
      activity and coincided with demethylation of DNA. In contrast, some lineage
      attributes, such as expression of IL-12R beta 2 (interleukin 12 receptor beta 2),
      required ongoing T-bet activity in mature T(H)1 cells and their progeny. These
      findings suggest that heritable states of gene expression might be maintained by
      continued expression of the inducing factor or by a mechanism that confers a
      stable imprint of the induced state.

PMID- 12055628
TI  - T(H) cell differentiation is accompanied by dynamic changes in histone
      acetylation of cytokine genes.
AB  - Naive T cells differentiate into effector cells upon stimulation with antigen, a
      process that is accompanied by changes in the chromatin structure of effector
      cytokine genes. Using histone acetylation to evaluate these changes, we showed
      that T cell receptor (TCR) stimulation results in early activation of the genes
      encoding both interleukin 4 and interferon-gamma. We found that continued culture
      in the presence of polarizing cytokines established a selective pattern of
      histone acetylation on both cytokine genes; this correlated with restricted
      access of the transcription factor NFAT1 to these gene regulatory regions as well
      as mutually exclusive gene expression by the differentiated T cells. Our data
      point to a biphasic process in which cytokine-driven signaling pathways maintain
      and reinforce chromatin structural changes initiated by the TCR. This process
      ensures that cytokine genes remain accessible to the relevant transcription
      factors and promotes functional cooperation of the inducible transcription factor
      NFAT with lineage-specific transcription factors such as GATA-3 and T-bet.

PMID- 12055629
TI  - Essential role of MD-2 in LPS responsiveness and TLR4 distribution.
AB  - Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a
      variety of cell types. MD-2 is associated with the extracellular domain of TLR4
      and augments TLR4-dependent LPS responses in vitro. We show here that MD-2(-/-)
      mice do not respond to LPS, do survive endotoxic shock but are susceptible to
      Salmonella typhimurium infection. We found that in MD-2(-/-) embryonic
      fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly
      resided in the Golgi apparatus, whereas TLR4 was distributed at the leading edge
      surface of cells in wild-type embryonic fibroblasts. Thus, MD-2 is essential for
      correct intracellular distribution and LPS-recognition of TLR4.

PMID- 12055630
TI  - Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains
      in T cell induced inflammation.
AB  - CD46 is a widely expressed transmembrane protein that was initially identified as
      binding and inactivating C3b and C4b complement products. We used mice that were
      transgenic for one of two human CD46 isoforms that differ in their cytoplasmic
      domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation on
      the immune response. We show here that CD46 can regulate inflammatory responses,
      either by inhibiting (CD46-1) or increasing (CD46-2) the contact hypersensitivity
      reaction. We found that engagement of CD46-1 or CD46-2 differentially affected
      CD8(+) T cell cytotoxicity, CD4(+) T cell proliferation, interleukin 2 (IL-2) and
      IL-10 production as well as tyrosine phosphorylation of Vav in T lymphocytes.
      These results indicate that CD46 plays a role in regulating the T cell induced
      inflammatory reaction and in fine-tuning the cellular immune response by bridging
      innate and acquired immunity.

PMID- 12055631
TI  - Facilitation at single synapses probed with optical quantal analysis.
AB  - Many synapses can change their strength rapidly in a use-dependent manner, but
      the mechanisms of such short-term plasticity remain unknown. To understand these
      mechanisms, measurements of neurotransmitter release at single synapses are
      required. We probed transmitter release by imaging transient increases in
      [Ca(2+)] mediated by synaptic N-methyl-D-aspartate receptors (NMDARs) in
      individual dendritic spines of CA1 pyramidal neurons in rat brain slices,
      enabling quantal analysis at single synapses. We found that changes in release
      probability, produced by paired-pulse facilitation (PPF) or by manipulation of
      presynaptic adenosine receptors, were associated with changes in glutamate
      concentration in the synaptic cleft, indicating that single synapses can release
      a variable amount of glutamate per action potential. The relationship between
      release probability and response size is consistent with a binomial model of
      vesicle release with several (>5) independent release sites per active zone,
      suggesting that multivesicular release contributes to facilitation at these
      synapses.

PMID- 12055632
TI  - Degree of language lateralization determines susceptibility to unilateral brain
      lesions.
AB  - Language is considered a function of either the left or, in exceptional cases,
      the right side of the brain. Functional imaging studies show, however, that in
      the general population a graded continuum from left hemispheric to right
      hemispheric language lateralization exists. To determine the functional relevance
      of lateralization differences, we suppressed language regions using transcranial
      magnetic stimulation (TMS) in healthy human subjects who differed in
      lateralization of language-related brain activation. Language disruption
      correlated with both the degree and side of lateralization. Subjects with weak
      lateralization (more bilaterality) were less affected by either left- or right
      side TMS than were subjects with strong lateralization to one hemisphere. Thus in
      some people, language processing seems to be distributed evenly between the
      hemispheres, allowing for ready compensation after a unilateral lesion.

PMID- 12055633
TI  - Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12
      cells.
AB  - Ca(2+)-triggered dense-core vesicle exocytosis in PC12 cells does not require
      vesicular synaptotagmins 1 and 2, but may use plasma membrane synaptotagmins 3
      and 7 as Ca(2+) sensors. In support of this hypothesis, C(2) domains from the
      plasma membrane but not vesicular synaptotagmins inhibit PC12 cell exocytosis.
      Ca(2+) induces binding of both plasma membrane and vesicular synaptotagmins to
      phospholipids and SNAREs (soluble N-ethylmaleimide-sensitive attachment protein
      receptors), although with distinct apparent Ca(2+) affinities. Here we used gain
      of-function C(2)-domain mutants of synaptotagmin 1 and loss-of-function C(2)
      domain mutants of synaptotagmin 7 to examine how synaptotagmins function in dense
      core vesicle exocytosis. Our data indicate that phospholipid- but not SNARE
      binding by plasma membrane synaptotagmins is the primary determinant of Ca(2+)
      triggered dense-core vesicle exocytosis. These results support a general lipid
      based mechanism of action of synaptotagmins in exocytosis, with the specificity
      of various synaptotagmins for different types of fusion governed by their
      differential localizations and Ca(2+) affinities.

PMID- 12055634
TI  - Visual features of intermediate complexity and their use in classification.
AB  - The human visual system analyzes shapes and objects in a series of stages in
      which stimulus features of increasing complexity are extracted and analyzed. The
      first stages use simple local features, and the image is subsequently represented
      in terms of larger and more complex features. These include features of
      intermediate complexity and partial object views. The nature and use of these
      higher-order representations remains an open question in the study of visual
      processing by the primate cortex. Here we show that intermediate complexity (IC)
      features are optimal for the basic visual task of classification. Moderately
      complex features are more informative for classification than very simple or very
      complex ones, and so they emerge naturally by the simple coding principle of
      information maximization with respect to a class of images. Our findings suggest
      a specific role for IC features in visual processing and a principle for their
      extraction.

PMID- 12055635
TI  - Neurobiological evidence for hedonic allostasis associated with escalating
      cocaine use.
AB  - A paradoxical aspect of the transition to drug addiction is that drug users spend
      progressively more time and effort to obtain drug hedonic effects that
      continually decrease with repeated experience. According to the hedonic
      allostasis hypothesis, increased craving for and tolerance to the hedonic effects
      of drugs result from the same chronic alteration in the regulation of brain
      reward function (allostasis). Here we show in rats that repeated withdrawals from
      prolonged cocaine self-administration produces a persistent decrease in brain
      reward function that is highly correlated with escalation of cocaine intake and
      that reduces the hedonic impact of cocaine.

PMID- 12055636
TI  - Myosin X is a downstream effector of PI(3)K during phagocytosis.
AB  - Phagocytosis is a phosphatidylinositol-3-OH-kinase (PI(3)K)-dependent process in
      macrophages. We identified Myo10 (Myosin-X), an unconventional myosin with
      pleckstrin homology (PH) domains, as a potential downstream target of PI(3)K.
      Myo10 was recruited to phagocytic cups in a wortmannin-sensitive manner.
      Expression of a truncation construct of Myo10 (Myo10 tail) in a macrophage cell
      line or cytosolic loading of anti-Myo10 antibodies in bovine alveolar macrophages
      inhibited phagocytosis. In contrast, expression of a Myo10 tail construct
      containing a point mutation in one of its PH domains failed to inhibit
      phagocytosis. Expression of Myo10 tail inhibited spreading, but not adhesion, on
      IgG-coated substrates, consistent with a function for Myo10 in pseudopod
      extension. We propose that Myo10 provides a molecular link between PI(3)K and
      pseudopod extension during phagocytosis.

PMID- 12055637
TI  - The systemic movement of a tobamovirus is inhibited by a cadmium-ion-induced
      glycine-rich protein.
AB  - Systemic movement is central to plant viral infection. Exposure of tobacco plants
      to low levels of cadmium ions blocks the systemic spread of turnip vein-clearing
      tobamovirus (TVCV). We identified a tobacco glycine-rich protein, cdiGRP,
      specifically induced by low concentrations of cadmium and expressed in the cell
      walls of plant vascular tissues. Constitutive cdiGRP expression inhibited
      systemic transport of TVCV, whereas suppression of cdiGRP production allowed TVCV
      movement in the presence of cadmium. cdiGRP exerted its inhibitory effect on TVCV
      transport by enhancing callose deposits in the vasculature. So cdiGRP may
      function to control plant viral systemic movement.

PMID- 12055638
TI  - Filamin A-interacting protein (FILIP) regulates cortical cell migration out of
      the ventricular zone.
AB  - Precisely regulated radial migration out of the ventricular zone is essential for
      corticogenesis. Here, we identify a mechanism that can tether ventricular zone
      cells in situ. FILIP interacts with Filamin A, an indispensable actin-binding
      protein that is required for cell motility, and induces its degradation in COS-7
      cells. Degradation of Filamin A is identified in the cortical ventricular zone,
      where filip mRNA is localized. Furthermore, most ventricular zone cells that
      overexpress FILIP fail to migrate in explants. These results demonstrate that
      FILIP functions through a Filamin A F-actin axis to control the start of
      neocortical cell migration from the ventricular zone.

PMID- 12055639
TI  - The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting.
AB  - Membrane proteins that are degraded in the vacuole of Saccharomyces cerevisiae
      are sorted into discrete intralumenal vesicles, analogous to the internal
      membranes of multi-vesiculated bodies (MVBs). Recently, it has shown that the
      attachment of ubiquitin (Ub) mediates sorting into lumenal membranes. We describe
      a complex of Vps27p and Hse1p that localizes to endosomal compartments and is
      required for the recycling of Golgi proteins, formation of lumenal membranes and
      sorting of ubiquitinated proteins into those membranes. The Vps27p-Hse1p complex
      binds to Ub and requires multiple Ub Interaction Motifs (UIMs). Mutation of these
      motifs results in specific defects in the sorting of ubiquitinated proteins into
      the vacuolar lumen. However, the recycling of Golgi proteins and the generation
      of lumenal membranes proceeds normally in Delta UIM mutants. These data support a
      model in which the Vps27p-Hse1p complex has multiple functions at the endosome,
      one of which is as a sorting receptor for ubiquitinated membrane proteins
      destined for degradation.

PMID- 12055656
TI  - In vitro effects of chemotherapeutic agents on human osteoblast-like cells.
AB  - Osteopenia is a complicating problem that may occur during and after treatment
      for childhood malignancy. Clinical studies suggest that chemotherapeutic agents
      directly affect osteoblasts in vivo. Since combinations of agents are used for
      treatment, we individually investigated the chemosensitivity of human osteoblast
      like cells to 11 of the chemotherapeutic agents used. The relative
      chemosensitivity of osteoblast-like cells representing different stages of cell
      differentiation was also examined. Cell numbers were evaluated following culture
      of an established human osteoblast-like cell line (MG63) for 3 days with
      clinically relevant concentrations of the chemotherapeutic agents. The
      chemosensitivity of MG63 cells was compared to that of a human osteoprogenitor
      cell line (HCC1) and primary osteoblast-like (HOB) cells derived from pediatric
      bone. Cell numbers were reduced by all agents in all cell types, although there
      was a varied response between agents at equimolar concentrations. In MG63 cells
      the lowest concentration of agent significantly reducing cell numbers varied
      between agents, for example, methotrexate (10(-7) M), vincristine (10(-9) M), and
      etoposide (10(-7) M) (all P <0.01). The less differentiated osteoblast phenotypes
      were significantly more chemosensitive at equimolar concentrations of
      methotrexate, vincristine, asparaginase, and dexamethasone than more
      differentiated phenotypes (all P <0.01). Furthermore, four agents significantly
      increased alkaline phosphatase (AP) activity in HOB cells. We conclude that
      individual chemotherapeutic agents added to osteoblast cell cultures reduce cell
      numbers, with osteoblast precursor cells being preferentially depleted. These
      results suggest that most of the agents may contribute to osteopenia in childhood
      malignancy by direct effects on cell numbers.

PMID- 12055657
TI  - Staphylococcus aureus fibronectin binding proteins A and B possess a second
      fibronectin binding region that may have biological relevance to bone tissues.
AB  - Staphylococcus aureus is a major human pathogen that has a propensity for
      targeting to bone tissues and thereby causing bone disease. A plausible
      hypothesis is that S. aureus targets to bone using the MSCRAMM family of surface
      proteins possessed by this organism. Two such proteins that have recently been
      shown to be important in bone infections are the S. aureus fibronectin binding
      proteins (FnBP) A and B. To identify fibronectin-binding domains from S. aureus
      that have biological relevance to bone, a phage display library of S. aureus
      genomic DNA was constructed and panned sequentially against immobilized
      fibronectin and cultured osteoblasts. Using this system, phage displaying a
      second fibronectin-binding region within the N-terminal part of FnBPA and FnBPB,
      which is distinct from the primary fibronectin-binding domain located within the
      D repeat region of these proteins, was isolated. Phage displaying this second
      region bound to both immobilized fibronectin and to osteoblasts and/or the
      extracellular matrix synthesized by these cells, thereby suggesting a biological
      relevance for these regions in S. aureus binding to bone tissues. Analysis of
      these binding regions for their ability to bind to other extracellular matrix
      proteins revealed a preference for fibronectin, with slight binding to fibrinogen
      and no binding to collagen or laminin.

PMID- 12055658
TI  - Optimal methods for processing mineralized tissues for Fourier transform infrared
      microspectroscopy.
AB  - Fourier transform infrared microspectroscopy (FTIRM) and infrared imaging (FTIRI)
      are techniques utilized in the analysis of bone mineral and matrix properties in
      health and disease. Since the spatial arrangement of bone tissue is conserved
      using FTIRM and FTIRI, quantitative data can be obtained on bone mineral
      (hydroxyapatite) crystalline size and composition, and on matrix structure and
      composition at discrete anatomic locations with a spatial resolution from
      approximately 7 mm (FTIRI) to 10 mm (FTIRM). To section bone for FTIRM and FTIRI,
      it must be preserved ("fixed") to maintain its properties, and embedded in a hard
      supportive material. Since most of the embedding media have components that
      spectrally overlap the components of mineralized tissues, it is critical to
      define optimal embedding and fixation protocols that have the least effect on
      mineral and matrix spectra. In the current study, the spectra of mouse calvaria
      in seven different fixatives and six different commonly used embedding media were
      assessed by FTIRM and FTIRI. The fixatives evaluated were absolute ethanol, 70%
      ethanol, glycerol, formaldehyde, EM fixative, and formalin in cacodylate or
      phosphate-buffered saline. The embedding media tested were Araldite, Epon, JB-4,
      LR White, PMMA, and Spurr. Comparisons were made to FTIR spectra obtained from
      unprocessed ground calvaria and to spectra of cryosections of unfixed tissue,
      fast-frozen in polyvinyl alcohol (5% PVA). Non-aqueous fixatives and embedding in
      LR White, Spurr, Araldite, and PMMA had the least effect on the spectral
      parameters measured (mineral to matrix ratio, mineral crystallinity, and collagen
      maturity) compared with cryo-sectioned calvaria and non-fixed, non-embedded
      calvaria in KBr pellets.

PMID- 12055660
TI  - Prevalence of H. pylori-infection in family members of H. pylori positive and its
      influence on the reinfection rate after successful eradication therapy: a two
      year follow-up.
AB  - INTRODUCTION: Living conditions (e. g. domestic crowding) may influence the
      infection rate. Some studies suggested that the reappearance of H. pylori in H.
      pylori positive patients after successful eradication therapy might be a result
      of transmission by H. pylori positive spouses. Therefore this study has been
      performed to evaluate the effect of the H. pylori status of family members on the
      reinfection rate of H. pylori positive patients after successful eradication
      therapy. METHODS: 108 H. pylori positive patients (64 male, 44 female, aged 48.7
      years, range 18-76 years) who presented with dyspeptic symptoms for upper GI
      endoscopy have been included into this study. H. pylori status has been defined
      by culture and/or histology, rapid urease test and serology. For eradication
      therapy patients received omeprazole 20 mg bd, clarithromycine 250 mg bd and
      metronidazole 400 mg bd. H. pylori status was controlled by (13)C-urea breath
      test 28 days (n = 96), 6 (n = 35), 12 (n = 28) and 24 months (n = 25) after
      eradication therapy. Additionally H. pylori status of 170 family members (82
      spouses, 68 children, 20 siblings/parents, aged 3-83 years) was defined by (13)C
      urea breath test (n = 167), upper GI-endoscopy (n = 2) or serology (n = 1).
      RESULTS: The eradication rate was 98 % (94/96). H. pylori prevalence in all
      family members was 40 % (56 % in spouses, 20 % in children). No reinfection has
      been found in successful eradicated patients within the two-years follow-up.
      DISCUSSION: These results suggest that reinfection is not dependent on the H.
      pylori prevalence in family members and that H. pylori reinfection after
      successful eradication therapy is an unlikely event.

PMID- 12055661
TI  - Evaluation of a new immunochromatographic based whole blood near patient test for
      the diagnosis of Helicobacter pylori infection.
AB  - BACKGROUND: Infection with H pylori is very common and may cause chronic
      gastritis, predisposes to gastric and duodenal ulcers, leads in some cases to
      gastric lymphoma and has been recognised as a class I gastric carcinogen. Rapid,
      inexpensive, reliable tests are needed to facilitate the diagnosis. METHODS: This
      prospective clinical study was undertaken to evaluate a new whole blood antibody
      test (helicoCare) in correlation to three tests for diagnosis of H pylori
      infection (histology, ELISA and rapid urease test). 304 patients (mean age 56.5
      years, range of 11-93 years) referred for esophagogastroduodenoscopy were
      included in this uni-centric study over a nine-month period. According to the
      guidelines for clinical trials in H pylori infection, patients with at least two
      positive tests were classified as positive for H pylori. RESULTS: 132 patients
      (43.4 %) were positive for H pylori, of which helicoCare identified 118 missing
      one gastric and one duodenal ulcer. 172 patients (56.6 %) were H pylori negative,
      of which helicoCare identified 163. Sensitivity was proven to be 89.4 % and
      specificity 94.8 %. In a special subgroup of 75 patients younger or equal to 45
      years, 28 patients were positive for H pylori (37.3 %). In this group a
      sensitivity of 85.7 % and a specificity of 97.9 % was found for the helicoCare.
      CONCLUSIONS: The helicoCare test showed sufficient sensitivity and satisfying
      specificity for H pylori diagnosis similar to or better than those of rapid
      urease test or ELISA. The helicoCare whole blood test may be useful for in-office
      H pylori diagnosis especially in patients under 45 years.

PMID- 12055662
TI  - [Clinical outcome of a cohort of 63 patients with hepatocellular carcinoma
      treated with octreotide].
AB  - Unresectable hepatocellular carcinoma (HCC) are associated with a poor prognosis.
      Recently, one controlled study reported a strikingly prolonged survival of
      patients with HCC who were treated with octreotide. Until other randomised
      controlled trials become available, this multicentric retrospective study
      therefore assesses the outcome of HCC-patients who received octreotide treatment.
      63 patients (53 males, 10 females) who had been treated with octreotide at 13
      participating German centres were included in the analysis. In 54 cases liver
      cirrhosis was present (25 Child-Pugh A, 20 Child-Pugh B, 7 Child-Pugh C, 2
      unknown). The liver disease was associated with alcohol abuse in 19 patients,
      alcohol and viral hepatitis in four patients, while 12 patients had only markers
      of past or present hepatitis B infection, 11 patients suffered of chronic
      hepatitis C infection, and four patients were seropositive for both hepatitis B
      and hepatitis C markers. The Okuda stage was stage I in 23, stage II in 33, and
      stage III in 7 patients. The patients initially received octreotide as a long
      acting release formula (20-30 mg/month) in 43 cases or through subcutaneous
      injection (dose 3 x 50-3 x 300 ug/day) in the remaining cases. 11 of the patients
      receiving subcutaneous treatment were later converted to the long-acting release
      form of the drug. At three months, a partial remission was achieved in two
      patients, while 22 tumours showed no change and 26 tumours progressed. At six
      months, 11 tumours showed no change, while 15 tumours progressed. The patients'
      median survival was 9 months (Okuda stage I 16 months, stage II 9 months, stage
      III 4 months). In conclusion, octreotide treatment did not result in markedly
      prolonged survival in this retrospective series of 63 patients.

PMID- 12055663
TI  - A randomised clinical trial comparing the efficacy of a herbal preparation STW 5
      with the prokinetic drug cisapride in patients with dysmotility type of
      functional dyspepsia.
AB  - AIM: To compare the efficacy of the herbal preparation STW 5 (Iberogast ((R)))
      and the research preparation STW 5-II with cisapride for treatment of patients
      with dysmotility type of functional dyspepsia. PATIENTS AND METHODS: After a
      diagnostic work-up and 7 days wash-out, 186 patients with dysmotility type of
      functional dyspepsia were randomly assigned in a double-blind, double-dummy study
      to one of three treatment arms (STW 5/cisapride-placebo; STW 5-II/cisapride
      placebo; cisapride/STW-placebo) for four weeks. Main outcome variable was the
      improvement of a dyspepsia-specific gastrointestinal symptom score. Symptoms were
      assessed three times during treatment and after six months follow-up. Hypothesis
      of non-inferiority was tested. Secondary endpoints were efficacy and tolerability
      assessments, recurrences and safety parameters. RESULTS: 137 patients were
      included in the confirmatory analysis. The lower limit of the confidence interval
      for both herbal preparations was above the pre-defined lower limit of the
      equivalence border and hypothesis of non-inferiority was proven for STW 5 and STW
      5-II. There were no statistical significant differences for the secondary
      endpoints. CONCLUSION: In this study STW 5 and the research preparation STW 5-II
      showed equivalent efficacy to cisapride for the treatment of patients with
      functional dyspepsia of dysmotility type.

PMID- 12055664
TI  - [High plasma levels of factor VIII and von Willebrand factor in a patient with
      portal vein thrombosis].
AB  - In portal vein thrombosis, various hypercoagulable conditions and inherited or
      acquired thrombophilias have already been described as predisposing factors. In a
      33-year-old man admitted to a hospital with upper abdominal pain, a partial
      portal vein and upper mesenteric vein thrombosis, respectively, and a complete
      splenic vein thrombosis were diagnosed. Further diagnostic procedures showed no
      evidence for local precipitating factors or any underlying infectious,
      paraneoplastic or inflammatory disease. Thrombophilia screening demonstrated
      elevated factor VIII levels (206 %) and von Willebrand factor levels (> 440 %).
      An acute-phase reaction was excluded. Oral anticoagulant therapy with
      phenprocoumon was started. Factor VIII and von Willebrand factor were
      reproducibly elevated to high activity levels over a period of 12 months in
      absence of acute or chronic inflammatory reaction. Increased levels of factor
      VIII and von Willebrand factor may play a pathogenetic role in the development of
      portal, splenic, and mesenteric thrombosis.

PMID- 12055665
TI  - [Cavernous haemangioma in the Muscularis propria of the oesophagus and in the
      paraoesophageal tissue].
AB  - This is a case report of a 45-year-old woman who presented herself in our
      hospital with increasing retrosternal tenderness to pressure, dysphagia, and
      symptoms of reflux oesophagitis. The clinical examination and laboratory results
      showed no pathological findings. Oesophagogastroduodenoscopy revealed a bluish
      livid, bulging mass from 32-38 cm aborally. A malignancy could not be excluded by
      biopsies with histological work-up, endoscopical ultrasound, nor CT-scan. By
      thoraco-abdominal surgery, a 5 cm large vascularised tumour of the outer layers
      of the oesophagus and the paraoesophageal tissue was resected. After
      intrathoracic oesophago-gastrostomy the patient could be discharged 17 days after
      surgery without further symptoms. Histology showed a benign tumour which was
      classified as cavernous haemangioma. To our knowledge, this is the first case of
      a haemangioma which involves the paraoesophageal tissue and the muscularis
      propria. The few published case reports of cavernous haemangioma of the
      oesophagus describe only an involvement of the mucosa and submucosa.

PMID- 12055666
TI  - [Long-Lasting Odynophagia and Haematemesis - the Only Clinical Signs of a
      Pemphigus vulgaris].
AB  - Odynophagia and dysphagia are clinical signs associated with a wide spectrum of
      potential causes. Our patient was an 84-year-old woman, who suffered from
      odynophagia and dysphagia for over 10 years. The interstinoscopy showed blister
      like lesions and signs of inflammation only in the proximal part of the
      oesophagus. The diagnosis of pemphigus vulgaris was supported by
      immunohistological results. Typical oropharyngeal and cutaneous lesions of
      pemphigus were missing in our patient. Involvement of the oesophagus is described
      in literature, but it seems to be underdiagnosed in clinical everyday's work.
      Restriction of the lesions to the oesophagus without oropharyngeal and cutaneous
      manifestation - as we have seen in our patient - is rare.

PMID- 12055667
TI  - [Molecular genetics of cholesterol cholelithiasis: identification of human and
      murine gallstone genes].
AB  - Cholesterol cholelithiasis is one of the most common gastroenterological diseases
      in Western countries. It is a polygenic disease resulting from disturbed biliary
      cholesterol homeostasis. Association studies identified six human gallstone
      candidate genes. Polymorphisms in the genes encoding the apolipoproteins B and E,
      phospholipid flippase ( ABCB4), cholesterol ester transfer protein ( CETP),
      cholesterol-7alpha-hydroxylase ( CYP7A1) and ileal bile acid transporter (
      SLC10A2) are correlated with gallstone prevalence. Quantitative Trait Locus (QTL)
      analysis localises additional unknown gallstone genes in inbred mice. Based on
      the natural variation of cholesterol gallstone susceptibility among different
      inbred strains, 5 lithogenic ( Lith) loci have been identified. Hepatobiliary
      transporters (e. g. bile salt export pump Abcb11) and key proteins of the
      lipoprotein metabolism (e. g. hepatic lipase Lipc) could be established as
      creedal candidate genes for Lith loci. The rapid progress of mouse and human
      genome projects provides the basis for the analysis of orthologous human LITH
      genes in gallstone patients, which might offer new prospects for individual risk
      assessment and molecular targets for stone prevention.

PMID- 12055668
TI  - [Anti-inflammatory properties of interleukin-10 in human Crohn's disease: much to
      learn, much to explore].

PMID- 12055669
TI  - [Aceruloplasminemia - a genetic iron storage disease].

PMID- 12055670
TI  - [Role of urgent colonoscopy in the diagnosis and treatment of severe diverticular
      bleeding].

PMID- 12055671
TI  - Clonality analysis in synchronous tumors of the female genital tract.

PMID- 12055672
TI  - Relationship between p53 pathway and estrogen receptor status in endometrioid
      type endometrial cancer.
AB  - We analyzed the mechanism of estrogen receptor (ER) loss and status of the p53
      pathway in 64 cases of endometrial cancer. 26.6% (17 of 64) of endometrial
      cancers lost ER. Methylation of the ER CpG island was significantly related to ER
      status (P = 0.0074). However, the methylation site of the ER CpG island differed
      between breast and endometrial cancers. The abnormal expression rate of p14ARF,
      MDM2, p53, and the p53 pathway were 7.8% (5 of 64), 32.8% (21 of 64), 25.0% (16
      of 64) and 53.1% (34 of 64), respectively. There was no significant difference in
      the overexpression of MDM2 between p53-positive cases (43.8%: 7 of 16) and p53
      negative cases (29.2%; 14 of 48) (P = 0.3595). Abnormal p53 was higher in grade 3
      tumors (55.6%; 5 of 9) than in grade 1 and 2 tumors (20.0%; 11 of 55) (P =
      0.0364). The abnormality of the p53 pathway was higher in grade 3 tumors (88.9%;
      8 of 9) than in grade 1 and 2 tumors (47.3%; 26 of 55) (P = 0.0294). However,
      there was no significant difference in abnormal p53 pathway between ER-negative
      and ER-positive cases. In endometrial cancer, ER CpG island methylation was the
      important mechanism of ER loss. However, there was no significant relationship
      between the p53 pathway and ER status.

PMID- 12055673
TI  - AIDS-related non-Hodgkin's lymphomas: from pathology and molecular pathogenesis
      to treatment.
AB  - In the highly active antiretroviral therapy (HAART) era, AIDS-related non
      Hodgkin's lymphomas (AIDS-NHL) and their treatment still represent an open issue,
      because HAART may not be sufficient to prevent the development of NHL. The
      present spectrum of AIDS-NHL includes systemic lymphomas, primary central nervous
      system lymphomas, and 2 rare entities, primary effusion lymphomas (PEL) and
      plasmablastic lymphomas of the oral cavity. The vast majority of systemic AIDS
      NHL belongs to 3 high-grade B-cell lymphomas: Burkitt's lymphoma (BL),
      immunoblastic lymphoma (IBL), and large-cell lymphoma (LCL). The pathologic
      heterogeneity of AIDS-NHL is correlated with the heterogeneity of the molecular
      lesions associated with these lymphomas. The molecular lesions associated with
      AIDS-BL involve activation of c-MYC inactivation of p53, and infection by Epstein
      Barr virus (EBV). EBV infection occurs in 40% of LCL cases and in 90% of IBL
      cases. Rearrangements of BCL-6 are detected in 20% of AIDS-LCL cases. In the
      presence of EBV infection, BCL-6 expressing AIDS-LCL fails to express the latent
      membrane protein 1 (LMP1) antigen. Conversely, AIDS-IBL are characterized by
      absent BCL-6 expression, absence of BCL-6 rearrangements, and frequent expression
      of LMP1. Consistently, the molecular pathways of viral infection and lesions of
      cancer-related genes associated with AIDS-NHL vary substantially in different
      clinicopathologic categories of the disease. The marked degree of biologic
      heterogeneity of AIDS-NHL is highlighted by their histogenetic differences,
      because AIDS-NHL are related to distinct B cell subsets (ie, germinal center [GC]
      or post-GC B cells). The phenotypic pattern of AIDS-BL and systemic AIDS-LCL
      closely reflects B cells residing in the GC, namely centroblasts and centrocytes.
      Conversely, the phenotype of AIDS-IBL, either systemic or localized primarily to
      the central nervous system, and AIDS-PEL reflects post-GC B cells in all cases.
      New information on the molecular and virologic pathogenesis of AIDS-NHL may serve
      as a point of attack for pathogenic-driven therapies. Moreover, a greater
      knowledge of other biologic features of these tumors may help investigators
      identify new potential targets for "intelligent" therapies.

PMID- 12055674
TI  - Reduced expression of PTEN correlates with breast cancer progression.
AB  - PTEN is a tumor-suppressor gene with phosphatase activity that is mutated in a
      variety of cancers. We analyzed a series of 34 invasive and 18 in situ breast
      cancers with known molecular status of the PTEN genotype using
      immunohistochemistry. Reduced PTEN protein expression was seen in 38% of invasive
      cancers and in 11% of in situ cancers. The frequency of reduced expression was
      highest in stage II and III cancers. Reduced expression also correlated with
      aneuploidy. In addition, in tumors with both in situ and invasive components,
      expression within the ductal carcinoma in situ portion tended to reflect the
      expression pattern of the invasive component. These data suggest that PTEN
      expression is frequently reduced in advanced breast cancers.

PMID- 12055675
TI  - Internet teleconferencing method for telepathology consultations from lung and
      heart transplant patients.
AB  - Current Internet-based teleconferencing techniques allow a referring pathologist
      to transmit real-time images from a microscope to a consultant, while maintaining
      a verbal conversation using Internet telephony. In our study, 50 randomly
      selected transbronchial biopsies from lung allograft recipients and 58 randomly
      selected endomyocardial biopsies from heart transplant patients were diagnosed by
      consultant pathologists using Internet-based teleconferencing methods. The
      referring pathologists acquired the real-time video images from the biopsies
      using a light microscope equipped with a phototube adapter and a video camera.
      The consultant pathologists viewed the processed images on a video monitor at 800
      x 600 resolution, using a standard microcomputer equipped with Netmeeting
      software, and directed the referring pathologist to move the slide under the
      microscopy and/or change image magnification. The validity of telepathology
      diagnoses was assessed with kappa coefficients. Consultations were completed in 5
      to 15 minutes per case. Sound transmission was unreliable, and in approximately
      25% of consultations the referring pathologist needed to "call back" to
      reestablish verbal communication. In all but 2 transbronchial biopsies there was
      agreement between the original diagnosis and the diagnosis by telepathology
      (kappa = 0.92). In 48 of 58 endomyocardial biopsies there was concordance between
      the 2 diagnoses (kappa = 0.692). Only 3 out of 10 of these discrepancies were
      clinically significant (kappa = 0.897). Internet-based teleconferencing
      techniques provide effective and relatively inexpensive tools for real time
      telepathology consultations. The technology is probably best suited for the study
      of small specimens from patients that require rapid diagnosis by a consultant.

PMID- 12055676
TI  - Epstein-Barr virus, p53 protein, and microsatellite instability in the adenoma
      carcinoma sequence of the stomach.
AB  - To elucidate the adenoma-carcinoma sequence in the stomach, we investigated
      Epstein-Barr virus (EBV) incorporation, p53 overexpression, and microsatellite
      instability (MSI) in gastric adenomas and carcinomas. The study involved 66 cases
      of gastric carcinomas within or adjacent to adenomas (adenoma-carcinoma cases),
      81 cases of simple adenomas (without carcinoma), and 306 de novo carcinomas
      (without adenoma focus). EBV incorporation was revealed in 1 (1.5%) of the
      adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo
      carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas
      in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding
      carcinomas (kappa = 0.63, P = 0.00). MSI was positive in 12.3% (8 of 65) of the
      adenomas in the adenoma-carcinoma cases and in 18.8% (12 of 64) of the
      corresponding carcinomas (kappa = 0.77, P = 0.00). In conclusion, EBV
      incorporation is not possibly associated with the gastric adenoma-carcinoma
      sequence, whereas the gastric adenoma-carcinoma sequence seems to be supported in
      terms of p53 overexpression or MSI. The transcriptional activation of EBV may
      occur relatively late (after the adenoma stage) in the gastric adenoma-carcinoma
      sequence.

PMID- 12055677
TI  - Genetics of synchronous uterine and ovarian endometrioid carcinoma: combined
      analyses of loss of heterozygosity, PTEN mutation, and microsatellite
      instability.
AB  - Synchronous development of carcinomas in the endometrium and ovaries is a fairly
      common phenomenon, but distinction of a single clonal tumor with metastasis from
      2 independent primary tumors may present diagnostic problems. To determine
      clonality and the occurrence of progression, we microdissected multiple foci from
      17 cases of synchronous endometrioid carcinomas and studied loss of
      heterozygosity (LOH), microsatellite instability (MI), and PTEN mutations. In 14
      of the 17 cases, genetic alterations were either homogeneous or found in only
      some of the foci. LOH was detected for 10q (4 cases), 17p (2 cases), and 2p, 5q,
      6q, 9p, 11q, 13q, and 16q (1 case each). Four cases had the MI phenotype with
      discordant MI patterns between both tumor sites, thus indicating a biclonal or
      triple clonal process. In 3 of 6 cases with PTEN mutations, identical mutations
      in both tumor sites indicated a single clonal neoplasm. Altogether, 14
      synchronous tumors were genetically diagnosed as follows: single clonal tumor,
      characterized by concordant genetic alterations in both tumor sites, including
      identical LOH, identical PTEN mutations, and/or identical sporadic allelic
      instability patterns (4 cases); single clonal tumor with genetic progression,
      homogeneous LOH or identical PTEN mutations in both tumor sites and progressive
      LOH in ovarian metastatic foci (2 cases); and double (7 cases) or triple clonal
      tumors (1 case), determined by discordant PTEN mutations, heterogeneous LOH,
      and/or discordant MI patterns. Thus, 35% of synchronous tumors were monoclonal,
      47% were polyclonal, and 18% were undetermined. The favorable prognosis of
      synchronous endometrioid carcinomas may be due to the occurrence of PTEN
      mutations in both independent and metastatic tumors, the MI-positive independent
      primary tumors, and the low frequency of LOH.

PMID- 12055678
TI  - High expression of p21WAF1/CIP1 is correlated with human hepatocellular carcinoma
      in patients with hepatitis C virus-associated chronic liver diseases.
AB  - p21(WAF1/CIP1) (p21) protein is a universal inhibitor of cyclin-dependent kinases
      and is regulated transcriptionally by p53, which is activated by DNA stress.
      Hepatocytes in chronic hepatitis receive several DNA stresses by lymphocytes and
      Kupffer cells. Therefore, we analyzed p21 expression of hepatocytes in hepatitis
      C virus (HCV)-associated chronic liver diseases and investigated the possible
      involvement of p21 in hepatocarcinogenesis. We examined p21 expression in 35
      cases of HCV-associated chronic hepatitis and 25 cases of HCV-associated liver
      cirrhosis by immunohistochemical analysis. The p21 labeling index (LI) was
      calculated as the ratio of positive cells to total cells. p21-positive
      hepatocytes were more numerous in areas of intense inflammation and spotty
      necrosis and areas close to fibrosis, and were increased according to the degrees
      of grading and staging. The p21 LI with liver cirrhosis was significantly higher
      than that with chronic hepatitis (14.4 +/- 5.9 versus 11.1 +/- 4.2, P = 0.014).
      The cumulative incidence of hepatocellular carcinoma (HCC) was significantly
      higher in the p21 LI >or=14% group than in the p21 LI <14% group (P = 0.0079).
      Multivariate analysis demonstrated that p21 expression can be recognized as an
      independent significant factor for HCC development (relative risk 5.00, P =
      0.039). p21 LI decreased significantly after interferon therapy. These results
      suggested that p21 is up-regulated by the stress of inflammation and fibrosis in
      HCV-associated chronic liver diseases and that high p21 expression might be
      related to hepatocarcinogenesis in cirrhotic patients.

PMID- 12055679
TI  - Origin of adenocarcinoma in a transplanted liver determined by microsatellite
      analysis.
AB  - Inadvertent transmission of neoplastic cells from an organ donor can occur at the
      time of transplantation. Determination of recipient versus donor origin of a
      tumor is crucial for patient management. This report illustrates the use of
      microsatellite (MS) analysis to determine the origin of adenocarcinoma arising in
      a liver transplant. The study patient was a 42-year-old male who had received a
      liver transplant for hepatitis C and alcohol-related cirrhosis. At the 1-year
      follow-up visit, a 1.5-cm liver mass was identified during routine ultrasound of
      the vascular anastamoses. A liver biopsy showed a moderately differentiated
      adenocarcinoma. Tumor, donor, and recipient DNA were isolated from the paraffin
      embedded liver biopsy, pretransplant donor liver biopsy, and the explant liver
      tissue, respectively. MS analysis was performed by polymerase chain reaction
      using 5 markers: D5S346, ACTC, D2S123, D18S34, and TP53. The allelic patterns of
      tumor DNA were identical to those of donor DNA and were distinct from the DNA
      profile of the recipient. The use of MS analysis clearly established that the
      adenocarcinoma was of donor origin.

PMID- 12055680
TI  - Zonal distribution of glomerular collapse in renal allografts: possible role of
      vascular changes.
AB  - Collapsing glomerulopathy (CG), an aggressive variant of focal segmental
      glomerular sclerosis, is a renal disease with severe proteinuria and rapidly
      progressive renal failure. The pathogenesis of CG is unknown. It strongly
      resembles human immunodeficiency virus (HIV)-associated nephropathy, but the
      patients are HIV negative. The characteristic glomerular lesion is capillary loop
      collapse with prominent podocytes filling Bowman's space. Interestingly, these
      glomerular changes are usually associated with severe tubulointerstitial injury,
      including tubular epithelial degenerative changes, microcystic dilation of
      several tubules, and interstitial inflammatory cell infiltrate. Recently, it
      became evident that the morphologic pattern of CG may appear not only in native
      kidneys, but also de novo in renal allografts, and that the pattern of CG in
      renal transplants is not always associated with severe proteinuria. Studies
      describing CG in renal allografts are all based on biopsies. We report 3
      allograft nephrectomy specimens that showed a zonal distribution of the
      characteristic collapsing glomerular changes with associated tubulointerstitial
      injury. All 3 kidneys had obliterative vascular changes. One nephrectomy specimen
      had chronic obliterative transplant arteriopathy, 1 had acute vascular rejection,
      and 1 had thrombotic microangiopathy. None of the patients had severe
      proteinuria. Our cases suggest that the morphologic pattern of CG in renal
      allografts may not represent the same disease process as CG in native kidneys and
      provide further evidence that collapsing glomerular changes do not define the
      disease entity of CG, but rather represent a pattern of renal injury. Among other
      factors, hemodynamic disturbance may play a role in the development of the
      pattern of CG in renal allografts.

PMID- 12055681
TI  - Atypical manifestation of a cytoplasmic antineutrophil cytoplasmic antibody (PR3
      ANCA)-associated vasculitis with involvement of aortic intima and parietal
      endocardium.
AB  - The traditional classification of vasculitis, based on the size of affected
      vessels, has meanwhile been extended by using antineutrophil cytoplasmic
      antibodies (ANCAs) as seromarkers in the differential diagnosis of different
      types of vasculitis. We report an autopsy case of fulminant generalized
      vasculitis positive for C-ANCA (1:320) and anti-proteinase 3 (PR3) antibodies
      (>100 U/mL) in a 63-year-old man. The unusually broad histologic spectrum
      included periarteritis nodosa-like lesions in medium-sized vessels and
      leucocytoclastic vasculitis in small vessels, as well as capillaritis. In
      addition, the left atrial and ventricular endocardium and the intima of the aorta
      thoracalis were patchily involved in the inflammatory process. Glomerulonephritis
      and/or immune complexes were not detectable by electron microscopy or
      immunohistochemistry. To the best of our knowledge, involvement of the aortic
      intima ("intimitis") and the parietal endocardium has not been described in PR3
      ANCA-positive vasculitis to date.

PMID- 12055682
TI  - Breast carcinoma metastasis within granulosa cell tumor of the ovary:
      morphologic, immunohistologic, and molecular analyses of the two different tumor
      cell populations.
AB  - Gynecologic metastasis of breast carcinoma is not an infrequent event, but
      metastases within another tumor is very rare. We report a case of unilateral
      ovarian tumor arising in a 63-year-old woman receiving tamoxifen therapy with a
      past history of breast carcinoma. The microscopic appearance was principally that
      of a granulosa cell tumor, but the presence of atypical cells closely admixed
      within the classical areas was reminiscent of metastasis from breast carcinoma.
      The diagnosis of this first reported case of breast carcinoma metastasis within
      granulosa cell tumor was supported by immunohistologic analysis. The diagnosis of
      tumor-to-tumor metastasis was also confirmed by molecular study using
      microdissections of samples from the initial breast tumor and from the subsequent
      ovarian tumor. When compared with normal tissue, carcinomatous cells in the
      breast tissue exhibited genomic abnormality at the same locus as the metastatic
      cells in the ovary. In contrast, granulosa cell tumor areas did not show any loss
      of heterozygosity or instability for the microsatellites analyzed.

PMID- 12055683
TI  - Mixed acinar-endocrine carcinoma arising in the ampulla of Vater.
AB  - We present a case of mixed acinar-endocrine carcinoma arising in the
      periampullary region of the duodenum. The patient was a 78-year-old male with a
      periampullary mass diagnosed during upper endoscopy. On gross dissection, the
      mass was 2.3 cm in diameter, noncystic, and confined to the duodenal submucosa.
      Microscopically, the tumor formed nests that were positive for amylase, trypsin
      (weakly), and synaptophysin (diffusely). Ultrastructurally, the tumor had 2
      populations of granules with mean diameters of 175 nm and 540 nm, consistent with
      endocrine and zymogen granules, respectively. These studies were consistent with
      a mixed acinar-endocrine carcinoma that arose in the duodenum. A review of the
      literature revealed 1 report of an acinar cell carcinoma arising in jejunal
      pancreatic heterotopia. The present article is the first reported case of an
      acinar cell carcinoma arising in the periampullary region of the duodenum,
      possibly in a focus of pancreatic heterotopia.

PMID- 12055684
TI  - Ms. Alice in healthcare wonderland--a modern tale of quality exceeding
      expectations.

PMID- 12055686
TI  - Cultural diversity in nursing practice.
AB  - This statement describes the features of an operational definition of cultural
      diversity as it is expressed in nursing practice, education, administration and
      research. (note: See Definitions which further defines specific terms related to
      cultural diversity).

PMID- 12055687
TI  - On planning a continuing education activity.

PMID- 12055685
TI  - Alternative health care delivery methodologies.

PMID- 12055688
TI  - What good is it anyway?

PMID- 12055689
TI  - Research facilitation: bypassing the barriers.

PMID- 12055690
TI  - Employee evaluation of BSN nursing graduates.

PMID- 12055691
TI  - Promoting the careful use of antibiotics (C.A.USE): an educational campaign for
      health care providers and communities in South Carolina.

PMID- 12055692
TI  - Birth wantedness reports: a look forward and a look back.
AB  - A number of checks can be done to assess reliability of attitudinal data
      pertaining to fertility. We ascertain how births that would be considered
      unintended, based on Time 1 reports of fertility intentions, are classified by
      respondents at a second interview after the birth occurred. The 1988 National
      Survey of Family Growth and a telephone reinterview allow us to identify
      respondents who initially intended to postpone or stop childbearing, but who then
      had a birth, and to analyze the reports they gave of the wantedness of the
      pregnancy leading to the birth. We also examine wantedness responses of women who
      claimed in 1988 that they intended to conceive within the next few years. Reports
      are compared across a range of respondent characteristics and circumstances,
      including changes in marital status since the initial interview. The analysis
      reveals nontrivial inconsistency between women's stated birth intentions and
      their reports about the wantedness of subsequent births. Details across subgroups
      are examined. Results also provide new information about effects of duration
      since birth on intention reports.

PMID- 12055694
TI  - Contribution of social and cultural factors to the decline in consanguinity in
      south India.
AB  - The data from the National Family Health Survey, 1992-1993, show that the extent
      of consanguinity is high (34.7 percent) in South India; 26.2 percent of women
      married close blood relatives, and 8.5 percent of women married distant blood
      relatives. A definite downward trend in the proportion of marriages between close
      blood relatives is observed. Education, age at marriage, religion and caste, and
      urban-rural childhood residence have significant independent effects on
      consanguinity. The multinomial logistic regression analysis reveals that in South
      India the downward trend in the proportion of marriages between close blood
      relatives is entirely explained by rising age at marriage and women's education
      over time.

PMID- 12055693
TI  - The determinants of delivery care in Kenya.
AB  - This paper examines the determinants of place of delivery and childbirth
      attendant in Kenya based on the 1993 Kenya Demographic and Health Survey data.
      The analysis utilizes multilevel logistic and multilevel multinomial regression
      models for the place of delivery and the type of childbirth attendant,
      respectively. The results show that delivery care in Kenya is determined by a
      wide range of factors: socioeconomic and cultural factors associated with the
      individual woman or her household, her demographic status or reproductive
      behavior relating to a specific birth, as well as availability and accessibility
      of health services within her community. In addition, a significant variation in
      delivery care behavior is observed between women and between communities,
      implying that there are unobserved factors within families and communities that
      have a significant effect on delivery care. The woman or family effect on
      delivery care is particularly strong, but varies by distance to the nearest
      delivery care facility.

PMID- 12055695
TI  - Seasonality of birth in nineteenth- and twentieth-century Austria.
AB  - We present an analysis of birth seasonality in nine geographical regions within
      Austria for two time periods, 1881-1912 and 1947-1959. In the early period,
      geography, climate, and agricultural patterns were related to birth seasonality.
      By the latter time period, these factors were no longer related to birth
      seasonality. We propose a "resilience hypothesis," which suggests two levels of
      causal influences on birth seasonality. First, underlying the three significant
      features of birth seasonality patterns around the world are only a small number
      of major causes. But, second, there are a multiplicity of minor causes that
      result in small perturbations in these otherwise resilient and consistent
      patterns.

PMID- 12055696
TI  - High fertility does not cause spontaneous intrauterine fetal loss: the
      determinants of spontaneous fetal loss in Egypt.
AB  - This study is concerned with a major, though relatively neglected, reproductive
      health issue: fetal loss. In particular, the determinants of spontaneous
      intrauterine mortality in Egypt are investigated with stress on the demographic
      determinants. To this end, a conceptual framework is developed. Using pregnancy
      history data from a national survey conducted in Egypt in 1995, the determinants
      of spontaneous intrauterine fetal deaths among currently married women aged 18-45
      are examined using multiple logistic models. It is found that the probability of
      intrauterine fetal loss rises with maternal age. The apparent positive
      association of the risk with gravidity is shown to be an artifact, due to the
      heterogeneity among women with respect to the risk of pregnancy loss, the
      consequent selection process, and reproductive compensation behavior according to
      the "success/failure" stopping rule. Therefore, high fertility cannot be said to
      cause spontaneous fetal loss. Two other features of a woman's reproduction are of
      strong significance, namely, her pregnancy history and spacing among pregnancies.
      Once a woman suffers from spontaneous fetal loss, the probability of undergoing
      further pregnancy losses rises sharply. And the shorter the pregnancy interval,
      the higher the probability of pregnancy loss. Pregnancies conceived after long
      intervals are less likely to end in loss.

PMID- 12055697
TI  - Racial/ethnic disparities in infant mortality: the role of behavioral factors.
AB  - Using the National Maternal and Infant Health Survey 1988 (NMIHS), a nationally
      representative sample of mothers, we investigate the role of behavioral factors
      in explaining racial/ethnic disparities in infant mortality. In particular, we
      focus on the following variables: weight gain during pregnancy, prenatal care
      utilization, exercise, vitamin use, and substance use during pregnancy. These
      analyses are conducted by modeling both time of death (neonatal vs. postneonatal)
      and cause of death (infections, perinatal complications, delivery complications,
      congenital malformations, SIDS, other causes) outcomes. Our results suggest that
      behavioral factors are partially responsible for observed race/ethnic
      differentials in infant mortality, but are not as important as sociostructural
      determinants such as SES.

PMID- 12055698
TI  - Public attitudes toward euthanasia and suicide for terminally ill persons: 1977
      and 1996.
AB  - This study replicates Singh's (1979) "classic" examination of correlates of
      euthanasia and suicide attitudes. The purposes of the current study were to
      assess (1) changes in public attitudes toward these voluntary termination of life
      practices, and (2) changes in the effects on attitudes of selected independent
      variables. I found Americans' approval of both euthanasia and suicide in 1996 to
      be higher than that in 1977. The increase in the approval of suicide, however,
      far outstripped that of euthanasia. Results of OLS regressions indicated that
      race, religious commitment, religious attendance, political identification, and
      suicide approval were statistically significant predictors of euthanasia
      approval. Only religious attendance and euthanasia approval were statistically
      significant predictors of suicide approval in both 1977 and 1996. The findings
      regarding euthanasia approval support those of Singh (1979); those regarding
      suicide approval do not. Triangulation of methods in future research is necessary
      to illuminate other aspects of these multifaceted issues.

PMID- 12055699
TI  - Age-heterogamy and Canadian union.
AB  - This study provides a much-needed exploration of the determinants of age
      discrepant unions in Canada. What little research has been conducted in this area
      of sociology of the family is now outdated. Further, the growing number of
      Canadians living in nonmarital cohabitation warrants their inclusion in any
      consideration of contemporary, heterosexual unions, and we have done so here.
      Utilizing multinomial logit modeling techniques, we analyze data drawn from the
      1995 Canadian General Social Survey. We find that cohabitations and remarriages
      are more likely to be age-discrepant than marriages, and that as age at union
      formation increases, so does the likelihood that the union will be age
      heterogamous. Although we hypothesized a positive relationship between education
      and the chances of age-heterogamous unions because the availability of eligible
      mates may decrease with education, we actually find an inverse association for
      women: a one-level increase in education decreases a woman's odds of entering an
      age-discrepant union by about 4 percent. We speculate that for women, greater
      education (economic position) may increase age-homogamy because they may be more
      economically attractive and thus more able to select a partner of their own age.

PMID- 12055700
TI  - Potential use of nuts for the prevention and treatment of coronary heart disease:
      from natural to functional foods.

PMID- 12055701
TI  - Frequent nut intake and risk of death from coronary heart disease and all causes
      in postmenopausal women: the Iowa Women's Health Study.
AB  - BACKGROUND AND AIM: Recent epidemiological studies suggest that there is an
      inverse association between the frequent consumption of nuts and the risk of
      coronary heart disease (CHD), and clinical investigations suggest that diets high
      in nuts may reduce serum cholesterol levels. This study assessed whether the risk
      of death due to CHD and all causes is reduced in postmenopausal women who
      frequently consume nuts. METHODS AND RESULTS: In 1986, 34,111 postmenopausal
      women with no known cardiovascular disease reported the frequency of their
      consumption of nuts and other foods, as well as other CHD risk factors. During
      approximately 12 years of follow-up, 3726 women died, 657 from CHD. After
      adjustment for multiple risk factors for CHD and dietary variables, there was an
      inverse but not statistically significant association between frequent nut
      consumption (two or more 28.5 g servings per week compared with less than one
      serving per month) and death from CHD (relative risk 0.81; 95% confidence
      interval: 0.60-1.11). There was also a weak inverse association between frequent
      nut intake and all-cause mortality (relative risk 0.88; 95% confidence interval:
      0.77-0.99, p for trend = 0.047). CONCLUSIONS: Frequent nut consumption may offer
      postmenopausal women modest protection against the risk of death from all causes
      and CHD.

PMID- 12055702
TI  - Effect of diet and treatment with statins on platelet-dependent thrombin
      generation in hypercholesterolemic subjects.
AB  - BACKGROUND AND AIM: Platelets are strictly involved in arterial thrombosis and
      their hyperactivity has been shown in hypercholesterolemia. It has been reported
      that drugs affecting cholesterol metabolism (statins) decrease cardiovascular
      events by lowering lipid levels or by means of non-lipidic actions such as the
      direct inhibition of platelet function. The aim of this study was to detect the
      effect on platelet-dependent thrombin generation (PDTG) of a reduction in
      cholesterol obtained by means of a lipid-lowering diet or treatment with statins.
      METHODS AND RESULTS: We compared PDTG (T0) in 144 hypercholesterolemic subjects
      (94 males and 50 females of child-bearing age, mean age 48.2 +/- 13.8, plasma
      total cholesterol 6.93 +/- 0.64, high density lipoprotein cholesterol 1.25 +/-
      0.14, triglycerides 1.15 +/- 0.19 mmol/L) and 70 normolipidemic controls (37
      males and 33 females, mean age 43.1 +/- 12.6. After six weeks on an appropriate
      diet, the patients were randomised to receive different statin therapies if there
      was no reduction in their lipid profile and/or PDTG (T1). They were re-evaluated
      six weeks later, and the drug doses were maintained or increased on the basis of
      the variables (T2). A final evaluation was made after a further six weeks (T3).
      All of the data were evaluated using ANOVA and Spearman's correlation coefficent.
      The results showed increased PDTG in hypercholesterolemic subjects (418.2 +/-
      29.2 mIU/mL, p < 0.001 vs controls). Diet alone did not reduce PDTG (380.2 +/-
      28.5 mIU/mL, p = 0.226 vs controls). At T2, simvastatin and atorvastatin
      significantly decreased PDTG (P < 0.001 vs T0-1) and low-density lipoprotein
      cholesterol (LDL-C). No correlation was found between the two variables in the
      simvastatin group (r = 0.16). Cerivastatin reduced PDTG without significantly
      decreasing LDL-C (p < 0.001 and p = 0.476, r = 0.14). Pravastatin and fluvastatin
      significantly reduced thrombin generation only at T3 (40 mg/day); pravastatin was
      also associated with a decrease in LDL-C (p < 0.01, r = 0.66). CONCLUSIONS: Our
      results confirm an increased PDTG in patients with type IIa hyperlipoproteinemia,
      which is not reduced by diet. Statins at different doses significantly decrease
      PDTG but do not correlate with a reduction in LDL-C.

PMID- 12055703
TI  - Adrenal C19 steroids and serum lipoprotein levels in healthy men.
AB  - BACKGROUND AND AIM: It has become apparent that dehydroepiandrosterone (DHEA)
      plays a protective role in atherosclerosis, but its influence on serum lipids has
      not yet been clarified. The aim of this study was to evaluate the association of
      endogenous adrenal C19 steroid hormones [(DHEA) and androstenedione (ASD)] and
      serum lipoprotein levels. METHODS AND RESULTS: The serum concentrations of
      dehydroepiandrosterone sulphate (DHEA-S), ASD, total and free testosterone,
      estradiol, total cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C),
      triglycerides, apolipoprotein AI (ApoAI) and apolipoprotein B100 (ApoB100) were
      measured in a sample of 88 healthy men. Statistical analysis using Spearman's
      correlation coefficient showed a positive correlation between DHEA-S levels and
      ApoAI (p = 0.034), a negative correlation between ASD and triglycerides (p =
      0.005), a positive correlation between ASD and LDL-C (p = 0.005), and a negative
      correlation between estradiol and HDL-C (p = 0.042). Multiple regression analysis
      revealed that DHEA-S is an independent factor for ApoAI, ASD an independent
      factor for triglycerides and LDL-C, and age an independent factor for ApoB100;
      estradiol was found to be a suggestive factor for HDL. CONCLUSIONS: The results
      suggest that the plasma levels of DHEA-S and ASD (adrenal C19 steroid hormones)
      correlate with the plasma lipid profiles of healthy men. It remains to be seen
      whether this profile is favourable.

PMID- 12055704
TI  - Effectiveness of screening for known mutations in Sicilian patients with
      "probable" familial hypercholesterolemia.
AB  - BACKGROUND AND AIM: More than 750 mutations in the low-density lipoprotein (LDL)
      receptor gene are currently known to cause familial hypercholesterolemia (FH),
      but the array of mutations varies considerably in different populations. The
      definition of essentially all the LDL receptor gene mutations in a population is
      therefore a prerequisite for the implementation of nation-wide genetic testing
      for FH. METHODS AND RESULTS: In this study, a screening strategy based on PCR
      enzymatic digestion and PCR-allele specific hybridisation procedures was used to
      evaluate the frequency distributions of 11 known mutations in a cohort of 214
      unrelated subjects meeting the diagnostic criteria of "probable" FH. We
      identified 20 mutation carriers (9.3%). One mutation (FH Palermo-1) occurred with
      a relatively high frequency, accounting for 7% of the entire study cohort. We
      also report the first observation of the receptor-negative mutation V408M
      (Afrikaner-2) in Italy. CONCLUSIONS: Our screening approach is not effective and,
      at least in our area, it is not a suitable alternative to the more expensive and
      time-consuming sequencing approach. However, our data suggest that it is possible
      to identify the molecular defect in about 10% of Sicilian patients with a
      clinical diagnosis of "probable FH" using a rapid laboratory diagnostic mutation
      panel. Four mutations were responsible for all of the diagnosed cases, and it
      could be reasonable to use this 4-mutation panel as a preliminary step before
      adopting a more complex laboratory approach.

PMID- 12055705
TI  - Benefits of sustained moderate weight loss in obesity.
AB  - Over the last few years, weight loss has been recognised as a key factor in the
      control and prevention of coronary heart disease, hypertension, type 2 diabetes,
      hyperlipidaemia, cardiorespiratory failure and other chronic degenerative
      diseases. It has been shown that even a modest loss of 5% of initial body weight
      can reduce, eliminate or prevent these disorders in a large proportion of
      overweight patients. The early benefits of weight loss can be explained by the
      direct effects of a low calorie diet, but the long-term effects can only
      partially be attributed to diet, physical exercise or behavioural modifications.
      Long-term studies have shown that a sustained moderate weight loss of 10%
      improves glycemic control as a result of reduced insulin resistance, the better
      control or prevention of hypertension, increased HDL-and decreased LDL
      cholesterol and VLDL triglycerides, improved diastolic function and the
      propagation of a cardiac stimulus that reduces the risk of ventricular
      arrhythmias. The health benefits of modest weight loss are particularly evident
      and useful when excess body fat is a major health hazard, as in the case of class
      III obesity (BMI > 40 kg/m2), which is often characterised by prevalent visceral
      fat accumulation. Baseline serum glucose, cholesterol, triglyceride, uric acid
      and blood pressure levels are usually higher in the upper body than is the case
      in peripheral obesity, and tend to decrease more in response to moderate weight
      loss. A therapeutic programme aimed at obtaining a gradual and moderate weight
      loss avoids the complications due to the rapid weight loss associated with
      inappropriate, unbalanced diets or even more harmful treatments. These
      complications include cholelithiasis and the subsequent risk of cholecystitis,
      lean body mass loss and a stable decrease in energy expenditure with a high
      probability of regaining weight (weight cycling syndrome). In conclusion, a large
      number of obese patients may be sensitive to a modest weight loss even without
      the achievement of ideal body weight. Sustained moderate weight loss by itself is
      definitely beneficial in obesity (especially "malignant" and "morbid" obesity),
      but also in diabetes, hypertension, hyperlipidaemia, cardiorespiratory diseases
      and other chronic degenerative diseases associated with any degree of excess body
      fat.

PMID- 12055706
TI  - [The fight over water fluoridation in Israel].
AB  - Water fluoridation in Israel was initially introduced on a municipal level in
      1981. Legislation in favor of national water fluoridation was approved in 1998.
      Over the last year an increasing campaign against the fluoridation project has
      become more and more evident. The material published by the opponents to
      fluoridation, distributed in pamphlets, daily journals and mass media resources,
      illustrate as in the USA, an endless and unrestrained "duel" between opponents
      and supporters of fluoridation. In Israel, in contrast to the USA, referenda are
      unprecedented, therefore, the political "battle field" is transferred to the
      municipal authorities and the Knesset. The pivotal component of the Israeli
      opponents to fluoridation regards the public's health and safety. Unscientific
      publications appear regularly in the daily journals and electronic mass media
      with no reference of supporting studies ever mentioned. The inevitable question
      addressed in this article is what are the best ways of action to be taken by the
      supporters of fluoridation is Israel. The main and most important mode of action
      against this campaign is, undoubtedly, continuous persuasion. Nevertheless, the
      continuous daily struggle of the supporters must be in a world-wide frame and be
      adjusted to the different target groups of the public. An effective confrontation
      should include nation-wide available publications (internet, daily papers and
      multimedia) with special emphasis on the important subjects (e.g. evidence based
      care, significance of toxic doses and the value of social justice), in a format
      comprehensible to the public and its leaders. The American experience helps us to
      understand that the opposition to water fluoridation will not diminished but, on
      the contrary, is expected to strengthen. We must look forward with no illusions
      and establish ways of action and cooperation by learning from past experience and
      from that of our collaborators. This will serve as the basis for the ongoing
      frank and persuasive efforts, derived from a deep and honest belief in the
      justice of our way.

PMID- 12055707
TI  - [Treatment of multiple recession-type defects in a young patient with esthetic
      demands].
AB  - Treatment of gingival recession has become an important therapeutic issue due to
      the increasing number of cosmetic demands from patients. Frequently, gingival
      recessions affect groups of adjacent teeth. In order to optimize the esthetic
      result all the contiguous recessions should be treated at the same time. The
      purpose of this article is to compare some techniques of root coverage in a
      patient with Miller class 1 recessions. A mean of 80% of root exposure was
      covered using the free gingival graft and free connective tissue graft with
      repositioned flap compared to 67% using coronally positioned flap over a
      connective tissue graft. In conclusion, partial root coverage and gingival
      augmentation with a good esthetic appearance were obtained by a one-step
      connective tissue graft procedure.

PMID- 12055708
TI  - [Intraoral autogenous onlay block bone grafting for implant dentistry].
AB  - The use of autogenous bone graft with endosseous implant for the reconstruction
      of alveolar ridge deficiencies has been reported with increasing frequency in the
      past two decades. These bone grafts were harvested mainly from extra oral sites.
      Various donor sites have been described in the literature including the
      calvarium, tibia and iliac crest, the latter being most common. Due to the need
      for hospitalization, general anesthesia and the great morbidity of surgery
      associated with these donor sites, alternative intra oral sources for graft
      harvest have been suggested. The most common sites for, being the mandibular
      symphysis and the mandibular ramus. For the repair of localized alveolar bone
      defects these donor sites are advantageous. In addition to the ease of donor site
      access and minimal morbidity, membranous bone grafts show less resorption, good
      incorporation and shorter healing times. The use of these bone grafts allow us to
      correct the alveolar ridge height, width and trajectory prior to implant
      placement thus not only enable a better surgical success, but also should enhance
      a better prosthetic results as well.

PMID- 12055710
TI  - [The overlooked chin trauma in children].
AB  - Children seldom experience major facial trauma. However, minor injuries such as
      facial lacerations, abrasions and dental trauma are more common and naturally get
      less attention. Children with TMJ trauma usually present with pain, limited jaw
      movement and even malocclusion. However, these findings are not always recognized
      and sometimes get overlooked when chin laceration is the only sign. Plain x-rays
      can contribute to the diagnosis but in many cases are inconclusive and are
      difficult to interpret. Often, there is a diagnostic dilemma, especially when the
      clinical findings are not clear and normal occlusion is hard to restore. We
      present 3 out of 12 children in whom we diagnosed condylar head fracture
      following minor facial trauma. All children had normal physiological occlusion.
      Most of them had mild clinical signs such as limited mouth opening, pain and
      tenderness upon palpation of the joint. Routine plain films were not conclusive.
      The diagnosis was made or confirmed with CT scan. Early diagnosis of TMJ fracture
      in children is mandatory for the prevention of long term functional and
      esthetically debilitating sequela. CONCLUSION: A thorough clinical examination
      and normal occlusion do not rule out condylar head fracture after chin trauma.
      Plain films are of limited value in the diagnosis of such fractures. CT should be
      considered for the evaluation of these children.

PMID- 12055709
TI  - [Self-applied topical fluoride products for children available in Israel. Part
      two: Mouthwashes].
AB  - The use of self applied topical fluoride products is considered, today, the most
      effective caries prevention measure. The daily or weekly/biweekly use of
      fluoridated mouth rinses, containing adequate concentrations of fluoride ion, has
      been shown to be an important adjunct in caries prevention and arrest. The
      purpose of this paper was 1. to review the various types of fluoridated mouth
      rinses, with regard to the type of fluoride compound and its effectiveness; 2. to
      focus on the fluoridated mouthrinses available for children in Israel in regard
      to concentration and additives, and 3. to give recommendations for rational and
      safe use. The mouthrinses are presented according to their concentration, showing
      Fluoride compound, additives, alcohol presence, flavor and manufacturer. The
      issues of safety in regard to ingestion of the rinse by small children are
      discussed. Rinses of no less than a 230-250 ppm are recommended to children of
      medium and high caries risk above the age of 6. The product should carry clear
      information regarding the type of fluoride compound, its concentration,
      instructions for use and age restriction. The products should be further
      protected by child proof caps.

PMID- 12055711
TI  - Avulsion and replantation.
AB  - The reported incidence of tooth avulsion ranges from 1% to 11% of all traumatic
      injuries to the permanent dentition. The maxillary central incisor is the most
      frequently avulsed tooth in the permanent dentition, and the most frequently
      involved age group is 7-10 years. This article reviews the present day knowledge
      on avulsion and replantation of permanent teeth. Treatment objectives are
      explained, and clinical management outside and inside the dental office are
      discussed. Detailed treatment protocols are provided considering the extraoral
      time and the degree of apical closure.

PMID- 12055712
TI  - [Periodontal disease--an additional risk factor for cardiovascular diseases?].
AB  - In 1989, a case-control study was published, linking between coronary heart
      disease and periodontal disease in the studied population. Since then, a number
      of additional studies, focused the attention to the possible role of dental
      infections in the pathogenesis of atherosclerosis. Some of these newer cohort
      studies, are prospective in nature, measuring incidence of the two diseases in
      large patient populations. The present article reviews these studies, and the
      proposed mechanisms which might explain the relationships between these two
      systemically distinct diseases.

PMID- 12055713
TI  - Digital cameras for clinical case presentations: how to live with them in
      dentistry?

PMID- 12055714
TI  - Management of esophageal varices.
AB  - The important developments have been made in the field of the portal hypertension
      and the variceal bleeding. Baverno meeting was organized to make consensus in
      different terminologies about the portal hypertension. Blockers of beta receptors
      are still mainstay in primary prophilaxis of variceal bleeding and endoscopic
      variceal ligation is ultimative. Octreotide and terlipressin are as effective as
      sclerotherapy in initial hemostasis, in addition, octreotid was after and
      efficacious in prevention of rebleeding. Endoscopic variceal ligation is showed
      to be superior to endoscopic sclerotherapy for variceal obliteration, especially
      sequential and simultaneous ligation. First line of treatment for gastric varices
      is cyanoacrilate glue. In assessment of variceal eradication and prediction of
      variceal recurrence endosonography plays important role.

PMID- 12055715
TI  - [Classification of gastroesophageal reflux disease and gastritis].
AB  - The gastroesophageal reflux disease (GORD) is frequent and causes by retrograde
      flow of the gastric content through incompetent gastroesophageal junction.
      Epidemiological studies have proved that GORD is associated with hearburn in high
      prevalence. In western countries several studies reported that 20-40% of adult
      population experience heartburn symptoms at least once in the year, approximately
      10% have symptoms weekly and 5% daily. Esophagitis was objectively defined as a
      mucosal damage and it was endoscopically verificated in 25% of patients. Indeed,
      GORD symptoms and esophagitis are in poor correlation and less than half of
      patients with heartburn symptoms had esophagitis on endoscopy. From 1989, Savary
      Monnier and Metaplasia-Ulcer-Stricture-Erosion (MUSE) endoscopically
      classification is in use. From 1994, LA (Los Angeles) classification of reflux
      disease is also in use by endoscopists. During its life cycle, gastric mucosa is
      exposed to different harmful agents and its response is restitution "ad integrum"
      on the beginning and at the end of process. First line defence is mucuse barrier
      which prevent contact between epithelial cell and possible irritant. Important
      role in mucuse layer plays prostaglandins. After several classification systems
      previously used, in 1991 Price introduced Sydney system gradation and gastritis
      classification. Pointing out importance of topographical differences in gastritis
      distribution, system has introduced 5 histological variations in its
      Morphological section: chronic inflammation, neutrophylic activity, glandular
      atrophy, intestinal metaplasy and H. pylori colonisation, with 4 points grading.

PMID- 12055716
TI  - [Is the only good Helicobacter a dead Helicobacter?].
AB  - The discovery of Helicobacter pylori (H. pylori) has revolutionised the
      pathophysiological and clinical approach to gastric and duodenal ulcer. Since the
      first paper identifying H. pylori was published only 19-20 years ago, it has been
      found out that this bacterium causes probably the commonest human infection. Like
      other revolutions in history, the original directions of the H. pylori story have
      changed in response to conflicting ideologies, observation, and practices. It is
      known that once H. pylori is acquired, colonisation continues for life unless the
      organism is eliminated by antimicrobial treatment or by the usually late-in-life
      development of the atrophic gastritis. If any recent achievement in the world of
      medicine is to be called revolutionary, then it is the discovery of the role of
      this spiral bacterium in the etiopathogenesis of gastritis, gastric ulcer,
      duodenal ulcer, gastric adenocarcinomas and gastric mucosa-associated lymphoid
      type (MALT) B-cell lymphomas. Essentially everyone who carries the organism in
      the gastric mucous layer has evidence of tissue reaction (termed chronic active
      gastritis), but most colonised persons remain asymptomatic for life. In the
      absence of treatment, the presence of H. pylori can be determined with a high
      degree of confidence by endoscopy (with culture, histologic examination, or
      urease testing of gastric biopsy specimens), by serologic testing, or by urea
      breath tests. After successful treatment, specific antibody levels decrease so
      slowly that serologic testing cannot be used to document success for at least 6
      months. In most patients, elimination of H. pylori changes the natural history of
      peptic ulcer disease and of gastric MALT lymphomas. It is now recommended that
      these patients have to be treated to eliminate H. pylori because the benefits
      seem to substantially outweigh the risks and costs. Currently, enthusiasts, drug
      companies, and the lay press are putting pressure on physicians to eliminate H.
      pylori from all patients, symptomatic or not, in whom it is detected. There is
      little evidence that this is appropriate, and management will continue to change
      as new knowledge emerges and socioeconomic environments change in ways that are
      relevant to H. pylori and clinical medicine.

PMID- 12055717
TI  - [Role of enteral nutrition in the treatment of chronic inflammatory bowel
      disease].
AB  - Malnutrition and specific vitamin and mineral deficiency together with growth
      retardation in children and delay in sexual maturation accompained Crohns disease
      and ulcerative colitis regularly. Supportive role of nutrition is to correct
      malnutrition, to heal specific nutritional deficiencies and enable normal growth,
      development and sexual maturation of children. Enteral nutrition, however, could
      be a primary therapeutical aspect as a change for pharmacological treatment. In
      this role, as succesful as steroids, initiate remmission in patients with
      intermediate or severe forms of disease without steroid like side. In adults,
      three meta-analyses confirmed therapeutical effects of enteral nutrition with
      remission rate of 60%, although steroids were more successful. These reports were
      valid only in Crohns disease. In ulcerative colitis neither parenteral or enteral
      nutrition had therapeutical effects without other types of treatment.

PMID- 12055718
TI  - [Endoscopic therapy of biliary obstruction].
AB  - Obstructive jaundice is consequence of several diseases of biliary ducts which
      cause biliary stasis. Constant finding is jaundice on skin and visible mucosal
      areas, acholic stool and dark urine. Obstruction could be permanent or
      intermittent. It could have rapid course with severe symptoms: biliary colics,
      signs of acute biliary ducts inflammation, acute pancreatitis or with atypical
      upper abdominal disorders. Asymptomatic biliary obstruction implies malignant
      disease. After initial clinical evaluation (history of disease, physical
      examination, biochemical analyses, ultrasound orientation) treatment of choice in
      diagnostic and management of biliary obstruction is endoscopic retrograde
      cholangiopancreatography (ERCP) proceeded with endoscopic sphincterotomy of
      sphincter Oddi. Further procedures depend on cause of obstruction.

PMID- 12055719
TI  - [Magnetic resonance cholangiopancreatography (MRCP): correlation with diagnosis
      using ERCP].
AB  - Magnetic resonance cholangiopancreatography (MRCP) is non invasive imaging
      technique able to provide projection images of the bile and pancreatic ducts.
      Using breath--hold and non-breath--hold acquisition techniques, have been
      employed in order to obtain MRCP images. Clinical applications of MRCP are
      evaluated from presenting references and from personal experience. The main
      indication for MRCP imaging was in evaluation of common bile duct obstruction,
      with aim of present the level, and its cause. The utility of conventional MR
      images to MRCP in the malignant lesion is already discussed. At the end, the
      utility of MR pancreatography in evaluation of the patients with pancreatic
      disease is discussed from both the literature and personal experiences. The
      clinical indications to perform ERCP in patients with pancreatic cancer may
      include palliative stent placement in patients with known non-resectable
      pancreatic carcinoma invading the common bile duct; obtaining tissue material in
      patients with atypical masses in the pancreatic head, particularly in the
      periampullary area; suspicion of intraductal neoplasm; difficult differential
      diagnosis between pancreatic cancer and chronic pancreatitis. The place for ERCP
      in future will be reserved for interventional procedures.

PMID- 12055720
TI  - The spectrum of the liver disease in the general population: lesson from the
      Dionysos Study.
AB  - Differently for what happened for the heart and the cardiovascular diseases, no
      data were available on the prevalence of the liver disorders in the general
      population. Based on these considerations we started planning a cohort study
      aimed to obtain data on how frequent liver disease was in the general population.
      Two comparable town in Northern Italy (Campogalliano, Modena, and Cormons,
      Gorizia) were selected on the basis of number of inhabitants, census and socio
      economic background, and 6.917 were screened with an overall compliance of 70%, a
      percentage adequate to validate this type of study. In each patient a semi
      quantitative, color-illustrated, food questionnaire including detailed questions
      on the use of alcoholic beverages was obtained in addition to a detailed physical
      examination to detect liver and the biliary diseases. Blood sample for ALT, AST,
      GGT, MCV and platelet count, and HBV and HCV markers were also taken.

PMID- 12055722
TI  - [Clinical features and diagnosis of inflammatory bowel disease].
AB  - The inflammatory bowel disease is common term for heterogenous group of the
      chronic recidivant idiopathic diseases with bowel inflammation as a common sign.
      Although within common term, traditionally we distinguish two diseases, Chrohns
      disease (CD) and ulcerative colitis (UC), in certain clinical situations those
      terms are not sufficient to describe all variants of inflammatory bowel diseases.
      Today increasingly, we have more and more knowledge about clinical,
      immunological, genetical heterogenicity in Crohns disease and ulcerative colitis.
      New evidences advocate theory that IBD represents folding subgroups of
      inflammatory bowel disorders in particular continuity with CD and UC as extremes
      of one spectrum.

PMID- 12055723
TI  - [Therapy of inflammatory bowel disease].
AB  - The term inflammatory bowel disease (IBD) represents different phenotypes of the
      idiopathic chronic inflammatory disease of gastrointestinal tract. Until now,
      ulcerative colitis, Crohns disease, indeterminate colitis and pouchitis were
      described. Treatment of these diseases is very complex with simultaneous need for
      individuality. Well-planned treatment requires answers on few questions for every
      treated: 1. What is the phenotype of IBD? 2. How extended is disease? 3. How
      active is disease? 4. What is the clinical course of disease until now? Answers
      on these questions should give complex patient evaluation according to wide
      accepted IBD protocol including activity estimation with one of activity disease
      indexes.

PMID- 12055721
TI  - [Interventional ultrasound in the treatment of acute pancreatitis].
AB  - OBJECTIVE: The objective of this study is to evaluate the possibilities of
      interventional ultrasonography in the treatment of liquid collections created
      during and after an acute pancreatitis. PATIENTS AND METHODS: Ultra-sound
      controlled percutaneous drainage of peripancreatic liquid collections was done in
      58 patients (44 men and 14 women, average age 47.8 within the span of 15-68) in
      the period between May 1995 and September 2001. Pseudocystitis of pancreas formed
      after an acute pancreatitis was drained in 19 cases, abscess collections were
      drained in 14 cases, and in 25 cases a catheter was entered in peripancreatic
      liquid collections and steatonecrotic masses in the initial phase of acute
      haemorrhagic necrotic pancreatitis. Pigtail catheters 5 to 7 F were placed to
      serve for drainage and instillation of medicaments. RESULTS: In the group of
      patients to whom a catheter was placed in liquid collections and steatonecrotic
      masses, two lethal outcomes were recorded. However, they were not the result of
      the intervention, but of emboly of lungs and coagulopathy. One patient with
      peripancreatic abscess collections was operated after the intervention. In other
      patients, ultra-sound controlled percutaneous drainage was successful. Before our
      intervention 22 patients had been operated, five of them twice and two of them
      three times. CONCLUSION: Ultra-sound controlled percutaneous drainage gives an
      important contribution in the treatment of the hardest forms of acute
      pancreatitis and represents a safe and less aggressive method in the treatment of
      liquid collections and steatonecroses formed during an acute pancreatitis.

PMID- 12055724
TI  - Models of screening program for colorectal cancer.
AB  - Colorectal cancer is one of the most frequent neoplasms in western countries,
      with an estimated 400,000 deaths per year throughout the world. The results of
      treatment vary widely, depending on the extent of the disease. In particular, the
      disease stage at diagnosis by the Dukes' modified classification is significantly
      correlated with prognosis. Colonoscopic polypectomy substantially reduces CRC
      incidence in comparison to that expected in the general population. These results
      are of particular relevance considering that people with adenomas are at
      increased risk for CRC. These observations strengthen the concept of effective
      population screening in view of the fact that adenomatous polyps are the most
      frequent neoplastic outcome of screening. Today we have new opportunities for CRC
      secondary prevention and it is time to start public awareness campaigns and
      involve gastroenterologists and general practitioners in a common effort.

PMID- 12055725
TI  - Endoscopic treatment of the benign and malignant esophageal stenosis.
AB  - Gastrointestinal endoscopy was born almost 40 years ago as diagnostic modality,
      but in last two decades with gradually developing of therapeutic possibilities
      gastroenterologists have taken an increasing role in the iinterventional
      treatment of many upper gastrointestinal problems. Modalities of treatment for
      esophageal stenoses were explained. Endoscopists should be aware that all of
      these methods has their limitations and they must be able to balance
      technological enthusiasm with full consideration of the patients qualities of
      life. All of this treatments are palliative, risky and only partially effective
      at best. They often need to be repeated. Even achieving a large lumen will not
      restore normal swallowing. The goal must be to restore "adequate but not perfect"
      swallowing, at lowest risk, cost and inconvenience to the patient.

PMID- 12055726
TI  - [Colorectal polyps].
AB  - The polyp is a focal mass that projects from the wall into the lumen. The term
      polyp is appropriate for gross, radiologic, and endoscopic usage and should be
      further modified to indicate topographic site, size, number and shape. Strictly
      spoken, a polyp consists of a head and a stalk, but also the lesions without a
      clear stalk, but still protruding into the lumen, are called (sessile) polyps. In
      this view, "polyp" means any lesion, which is circumscribed and raised above
      normal surrounding mucous membrane so that it is visible to the naked eye.
      Clinicians sometimes even use "polyp" to refer to any tumor detected in the large
      intestine. The term polyp does not hold any information about the pathological
      nature of the lesions. Some polyps (benign, non-neoplastic polyps) do not have an
      increased potential for becoming malignant, while other polyps (adenomas,
      neoplastic polyps) are precancerous, which may progress to malignant lesions
      (carcinomas). Thus polyps must be biopsied or resected to determine their
      histological type and establish a complete diagnosis.

PMID- 12055727
TI  - [Endoscopic methods of treatment of precancerous lesions of the colon].
AB  - The endoscopic method--colonoscope, has become the tool of choice for diagnosing
      many colonic disorders, including the acute and chronic inflammatory bowel
      disease, lower gastrointestinal bleeding, benign and malignant tumors, and
      various others abnormalities appearing on the radiographs. The colonoscope is
      also useful and become the main confirmation method in screening for and
      monitoring colonic cancer. In the same time, colonoscopy offers numerous
      therapeutic options. The colonic polyps, well-known colonic precancerous lesions,
      with incidence ranges from 7 to 50%, can be removed completely during the
      colonoscopy, with a snare or biopsy forceps (polypectomy). Early cancers limited
      to the mucosal layer (intraepithelial cancer or carcinoma in situ) can be treated
      endoscopically too (mucosectomy), as well as various gastrointestinal bleeding
      (with sclerotherapy, electrocoagulation, APC, laser-fotocoagulation),
      inflammatory and postsurgical strictures (endoscopic dilation), and foreign
      bodies in the rectum and sigma (endoscopic extraction).

PMID- 12055728
TI  - [Expert systems in gastroenterology].
AB  - Expert systems are the software systems developed by the application of the
      various intelligence, which could successfully compete to peoples-experts, and
      have the consultant function with the characteristics of the explanations and the
      advices in some specific domain. These are, in essence, the intelligent
      information systems, which consists several thousands of the rules from the
      definite problem field and which are capable to explain their decisions. The
      knowledge systems are lesser software systems, also developed by means of the
      technique of the artificial intelligence which are usually less successful in
      some field of knowledge of the experts. In the paper are presented the basic
      characteristics three most often applied expert systems in gastroenterology:
      Quick Medical Reference (QMR), HEPAT, ILIAD.

PMID- 12055729
TI  - [Importance of the Barrett esophagus in the development of esophageal
      adenocarcinoma].
AB  - Arising of esophageal carcinoma, particularly adenocarcinoma of esophagus could
      be prevented. With correct nutrition, avoiding of substances which could lead to
      carcinogenesis patients could help himself in esophageal carcinoma prevention.
      Thats for, broad education of population on state level is needed. Duly
      discovering and treatment of reflux disease is a key factor in preventing of
      complications, especially Barretts esophagus which is premalignant lesion by
      itself. Program of long term endoscopic and histology follow up contribute in
      esophageal adenocarcinoma prevention or its early discovering in a stage of
      curability.

PMID- 12055730
TI  - [Smoking epidemics. Epidemiology, risk factors, and preventive measures].

PMID- 12055731
TI  - [Impact of mass communication media on an anti-smoking campaign].
AB  - OBJECTIVE: To assess the impact of the mass media (MM) on smoking cessation
      process in Mexico. MATERIAL AND METHODS: Between June 1998 and May 1999, the
      effects of an anti-smoking mass media campaign and alternative strategies were
      evaluated, by comparing the monthly sales average of all smoking-cessation aid
      products before and after marketing a new nicotine patch. Student's t paired and
      unpaired t tests were used to compare sales. RESULTS: Total sales increased from
      24,206 +/- 4,558 to 55,604 +/- 8,993 (p < 0.0001). It was estimated that 1,853
      smokers tried to quit and 96 per day succeeded with a single product after the
      campaign. Alternative strategies to get similar results indicate that the
      programs of a single public sector institution could help 501 persons attempt
      quitting smoking and six to accomplish it per day. CONCLUSIONS: The mass media
      have a powerful effect on smoking cessation practices; the involvement of more
      public institutions may accomplish similar results as the private sector.

PMID- 12055732
TI  - [From tobacco use to other drugs use: does the early use of tobacco increase the
      probability of use of other drugs].
AB  - OBJECTIVE: To assess the likelihood of substance abuse predicted by age of first
      exposure to tobacco. MATERIAL AND METHODS: Data from the 1998 National Household
      Survey on Addictions in urban areas were analyzed. RESULTS: The age period of
      greater likelihood of drug experimentation is between 15 and 19 years; only 5.6%
      of drug users and 13% of alcohol beverage drinkers reported having experimented
      with drugs before trying tobacco. The probability of heavy drinking and
      dependence was higher at early ages of first exposure to tobacco and decreased
      with increasing age. Experimentation with drugs, continued use, and multiple drug
      use, are more frequent among smokers who started before 15 years of age.
      CONCLUSIONS: Early tobacco use increases the likelihood of substance abuse.

PMID- 12055733
TI  - [Epidemiology of smoking in Europe].
AB  - Tobacco is the most important preventable cause of mortality in European
      countries, accounting for over half a million deaths per year. A review is
      presented on the epidemiology of tobacco smoking in Europe, using a comprehensive
      approach on the health effects of smoking, the prevalence of tobacco consumption,
      and its evolution in the past decade. Tobacco industry efforts to promote and
      maintain smoking through production and pricing are also reviewed. Thirty out of
      every 100 European adults smoke everyday and one of every ten adults smokers will
      die from tobacco smoking; a higher ratio of 1:15 is found in Eastern Europe. The
      prevalence of smokers is decreasing among young adults in some European
      countries, while it is increasing among young women in Southern and Eastern
      Europe. Smoking cessation and prevention interventions should be implemented,
      such as banning smoking in public areas, banning direct and indirect advertising
      of tobacco products, crop reduction, and rising cigarette prices. These
      interventions should be designed, coordinated, and developed by and among the
      different sectors involved in tobacco control initiatives, together with social
      network at the local, regional, and national levels, with the support of national
      and international organizations.

PMID- 12055734
TI  - [Treatments to quit smoking, available in Mexico].
AB  - OBJECTIVE: To describe smoking cessation therapies available in Mexico. MATERIAL
      AND METHODS: Literature review of meta-analysis, controlled clinical trials, and
      behavioral therapy studies. RESULTS: Smoking cessation pharmacotherapy
      interventions showed a good chance of success on average, expressed as the ratio
      of the active drug vs. placebo cessation therapy outcomes (ratios of 39, 78, 79,
      117, and 119%, for nicotine chewing gum, bupropion, nicotine patch, inhaler, and
      nicotine nasal spray, respectively). Behavioral therapy showed satisfactory
      results, (OR = 3.8) however, more research is needed to establish its
      effectiveness. CONCLUSIONS: Emphasis is made on the need to combine behavioral
      therapy with pharmacotherapy, to increase the likelihood of successful smoking
      cessation.

PMID- 12055735
TI  - [Tobacco use in the region of the Americas: elements for a program of action].
AB  - Tobacco consumption is one of the most important public health challenges faced
      in the Americas. This is not only due to the great number of deaths attributable
      to smoking, many of which are premature, but also to the high economic and social
      costs of medical care and the burden of disease and disability imposed by tobacco
      consumption on health systems and on the population. In the regional
      epidemiologic situation. South American countries are characterized by the
      highest consumption rates, followed by the Andean region and Mexico; Central
      American and Caribbean countries have the lowest smoking prevalences. Only the
      United States and Canada have been able to hold back the smoking epidemic; the
      rest of the hemisphere shows stable or increasing smoking rates. In the region,
      age of smoking initiation has decreased and the number of women who smoke has
      increased. This article reviews the current tobacco control measures in Latin
      American legislations and analyzes selected regional characteristics such as the
      structure of young populations, control measures that are weak or scarce, and the
      world production of tobacco. There is a compelling need to establish economic,
      population-based, and legislative procedures leading to a gradual reduction of
      the current tobacco consumption rates. This paper advances a comprehensive action
      plan against tobacco consumption.

PMID- 12055736
TI  - [To smoke or not to smoke, in restaurants, hotels, and bars].
AB  - A MEDLINE search was conducted to identify relevant references, to review the
      information on adverse effects of tobacco smoking and environmental tobacco smoke
      (ETS). Occupational exposure to ETS causes significant damages to food industry
      workers. High levels of mutagenic substances have been demonstrated in restaurant
      air as well as in the urine samples from those workers. Exposition to 3
      aminophenyl, a hemoglobin-associated carcinogen. The best way to protect these
      workers is the reduction of tobacco smoking in restaurants, hotels, bars and
      taverns. In restaurant workers, ETS attributable risk for lung cancer is evident.

PMID- 12055737
TI  - [Risks of active and passive smoking].

PMID- 12055738
TI  - [Impact of smoking on mortality in Mexico].

PMID- 12055739
TI  - [Perspectives of research-action against tobacco use in Mexico. The
      Interinstitutional Meeting of Cocoyoc].

PMID- 12055740
TI  - [Mortality trends in cancer attributable to tobacco in Mexico].
AB  - OBJECTIVE: To describe the mortality trends of cancer attributable to tobacco
      smoking, particularly lung cancer, for the 1980-1997 period in Mexico. MATERIAL
      AND METHODS: Mortality trends were analyzed for each type of cancer associated to
      tobacco smoking, according to the International Classification of Diseases (ICD).
      Crude and adjusted mortality rates were estimated for the period between 1980 and
      1997, by age, gender, basic death cause, and year of death. The gender ratio and
      the relative proportion were estimated for cases in the 35-64 age group and for
      the entire study population. Age population projections by Consejo Nacional de
      Poblacion (National Population Council), were used as denominators (1970-2010).
      RESULTS: The gender ratio for mortality rates for lung, esophageal, oral cavity
      and pharyngeal cancer was 2.10:1.00 (male:female). The gender ratio for laryngeal
      cancer was striking: 4.21:1.00, probably due to the higher prevalence of male
      tobacco smokers. The estimated relative proportion, using the total mortality due
      to malignant cancers between 1980-1997, was 12.31% for lung cancer, 1.71% for
      larynx cancer, 1.55% for esophageal cancer, and 1.49% for oral cavity/pharyngeal
      cancer. Previous tobacco smoking was correlated with the mortality rate trends
      for lung cancer (beta: 0.910, IC 95%: 1.097-1.797, R2 0.827). For the poorest
      social groups by federal entity, the correlation was inverted (beta: -0.510, IC
      95% -0.170, -0.039, R2: 0.260). CONCLUSIONS: In Mexico, increased tobacco
      smoking, improved cancer diagnosis, and the demographic transition, are probably
      the main factors determining cancer mortality rates. However, other lifestyle
      associated variables, such as urbanization, physical activity, carotenoid intake,
      and other dietary and toxic substances like alcohol, may also influence the
      morbidity and mortality rates. Although tobacco-related cancer is a fast-growing
      public health problem having a poor prognosis, tobacco smoking, the main risk
      factor, could be eliminated by health education and promotion, together with
      publicity regulation and healthy taxation policies.

PMID- 12055741
TI  - [The Cuernavaca Declaration for a tobacco smoke-free environment].

PMID- 12055742
TI  - [Mortality attributable to tobacco use in Mexico].
AB  - OBJECTIVE: To study the mortality attributable to tobacco and alcohol
      consumption. MATERIAL AND METHODS: Deaths occurring in 1998, abstracted from the
      mortality statistics registry in the Coyoacan District of Mexico City, were
      classified by cause as: Cardiovascular Diseases, Respiratory Diseases, and
      Neoplasias. Relatives of the deceased were interviewed to answer a questionnaire
      on tobacco smoking and alcohol drinking. RESULTS: Smoking during the last ten
      years of life was significantly associated with cardiovascular disease in men
      aged 70 years or older (OR 2.06, 95% CI 1.18-3.58). Persistent smoking in the
      last year of life was significantly associated with deaths from neoplasias and
      respiratory diseases in women aged 70 years or older (OR: 7.24, 95% CI 1.71
      30.53; OR: 4.82 95% CI 1.41-16.50, respectively). The regression model for
      cardiovascular disease showed that subjects with intense tobacco consumption were
      almost twice as likely to die from cardiovascular disease (OR 1.83, 95% CI 1.1
      2.8, p < 0.01). The population attributable risk for cardiovascular disease was
      45%. CONCLUSIONS: Tobacco smoking is an important predictor of dead among the
      elderly in Mexico. Tobacco control programs should also be targeted to the
      elderly.

PMID- 12055743
TI  - [Smoking and its association to heart ischemic disease].
AB  - OBJECTIVE: To assess the impact of cigarette smoking on coronary heart disease
      (CHD) and to propose a simple and efficient method to estimate its attributable
      fraction (AF). MATERIAL AND METHODS: A matched case-control study was conducted
      in the Regional Hospital of Instituto Mexicano del Seguro Social (Mexican
      Institute of Social Security) in Morelos State, Mexico, from May to June-2000.
      Cases were 80 prevalent and incident patients with CHD. One-hundred-sixty
      controls matched by sex and age were randomly selected from the outpatient
      clinic. The attributable fraction was obtained through summary estimators,
      variances, and confidence intervals for matched designs with more than one
      control per case. RESULTS: The prevalence of cigarette smoking previous to the
      coronary event was 80%, compared to 62.1% in controls. Mantel-Haenszel odds
      ratios showed a positive association of cigarette smoking with CHD (OR, 6.7; 95%
      CI, 3.2-13.8). The attributable fraction among the exposed was 85% (95% CI, 74
      95) while the population attributable fraction was 56% (95% CI, 45-66). The AF in
      exposed was 65% for males (95% CI, 53-77) and 31% for females (95% CI 14-47).
      CONCLUSIONS: The long-term smoking AF on CHD is greater than 85%. Such a high AF
      should be countered with the implementation of primary prevention measures to
      encourage smoking cessation and with smoking cessation clinics for active
      smokers. These are the two most important public health interventions to prevent
      CHD and a variety of chronic diseases.

PMID- 12055745
TI  - [The program of action against smoking].

PMID- 12055744
TI  - [Trends of tobacco use among new students at the Autonomous National University
      of Mexico, from 1989 to 1998].
AB  - OBJECTIVE: The purpose of this study was to describe the tobacco smoking patterns
      in students in the Universidad Nacional Autonoma de Mexico system, (Mexico's
      National Autonomous University, UNAM), between 1989 and 1998. MATERIAL AND
      METHODS: This is a time-series, cohort study conducted in the year 2000. The
      overall prevalence of smoking, age- and sex-specific prevalence rates, and the
      prevalence of subjects smoking 11 or more cigarettes daily, were estimated for
      103 582 new students aged 14 to 25 years. The same subjects were contacted for a
      second time, to estimate the cumulative incidence of smoking during the high
      school period. Associations were tested using a chi-squared test for trends, and
      prevalence odds ratios were obtained using a logistic regression model. RESULTS:
      The overall prevalence of smoking increased during the study period, mainly after
      1993 among younger and female subjects. A higher smoking incidence was found
      among students of higher economic level. During the high school years, the
      incidence of smoking initiation was 12% for females and 19% for males. The
      probability of smoking increased with older age, male gender, and at the final
      years of the study period. CONCLUSIONS: In the last decade, evident changes in
      young students' smoking patterns have occurred. Antitobacco campaigns targeting
      young people should be implemented.

PMID- 12055746
TI  - [Prevalence of smoking and low school performance, among students 11-24 years of
      age in the state of Morelos, Mexico].
AB  - OBJECTIVE: To assess the association between self-reported academic performance
      and tobacco experimentation and established tobacco use among adolescents and
      young adults in Morelos State, Mexico. MATERIAL AND METHODS: A population-based,
      cross-sectional study was carried out in 72 administrative areas from all 33
      municipalities of Morelos State (urban, semi-urban and rural areas). A total of
      13,293 adolescents and young adults aged 11 to 24 years were randomly selected
      from public schools. Data were collected using a self-administered questionnaire.
      Multinomial logistic regression models were fitted with smoking habit as the
      dependent variable with three categories (never a smoker, occasional smoker, and
      regular smokers). RESULTS: The prevalence of occasional smokers was 14.9% (95%
      CI: 14.1-15.7) among females and 27.3% (95% CI: 26.1-28.4) among males. The
      corresponding figures for females and males for established smokers were 6.1%
      (95% CI: 5.6-6.6) and 13.1% (95% CI: 12.2-13.9), respectively. Academic
      performance self-reports were found to be inversely proportional to occasional or
      regular tobacco use. In women, the association with current tobacco consumption
      was 5.1 times higher (95% CI: 2.5-10.4) in women with a yearly grade average of
      six or less, in comparison to those with scores of ten or nine. The same pattern
      was observed in men (OR = 4.2; 95% CI: 2.7-6.7), with a significant linear trend
      both in both women and men. CONCLUSIONS: These results evidence that tobacco
      consumption is related to low academic performance. This relationships is
      determined by complex lifestyle patterns of adolescents.

PMID- 12055747
TI  - [Smoking among health professionals of the Mexican Social Security Institute,
      Morelos].
AB  - OBJECTIVE: To assess the prevalence of tobacco smoking by work type among
      healthcare workers of Instituto Mexicano del Seguro Social (Mexican Institute of
      Social Security, IMSS), in Morelos State, Mexico. MATERIAL AND METHODS: A cross
      sectional was conducted in 3,133 healthcare workers in the 23 medical units of
      IMSS Morelos District, from October 1998 to March 2000. Data were collected using
      a self-applied questionnaire on tobacco smoking for different life-stages, some
      demographic characteristics, and work type. The prevalence rates of smoking and
      95% confidence intervals (95% CI) were estimated by age groups, gender, and work
      type. RESULTS: A total of 3,133 employees participated; 53.4% (95% CI 50.8-56.8)
      of men and 27.4% (95% CI 25.4-29.3) of women reported having smoked tobacco some
      time in their lives. The prevalence of current smoking was 28.3% (95% CI 25.6
      31.0) and 14.4% (95% CI 12.8-15.9) in men and women, respectively. Among men,
      physicians have a lower prevalence (20.9%) of current smoking than that of other
      workers; for example, the prevalence was 26.6% among technicians and 33% among
      administrative personnel. Women in general had a lower prevalence than men in all
      categories, and in nurses it was still lower t(12.5%) than that of female
      physicians (16%). CONCLUSIONS: The prevalence of tobacco smoking in healthcare
      workers of IMSS Morelos was lower than that of the general population.
      Nevertheless, it is necessary to keep working on tobacco control programs to
      encourage smoking cessation among healthcare workers and make them aware of the
      positive role they may play in promoting programs to stop tobacco smoking and
      nicotine addiction.

PMID- 12055748
TI  - [The epidemics of smoking in the Americas].

PMID- 12055749
TI  - [Tobacco use in Mexican households: results of the Income and Expenses Survey of
      Households, 1984-2000].
AB  - OBJECTIVE: To analyze selected determinants of tobacco consumption in Mexican
      homes. MATERIAL AND METHODS: Data from the National Household Income and
      Expenditure Survey, 1984-2000, were analyzed. The analysis was conducted for the
      years 1984-1992 and 1994-2000. The likelihood of tobacco consumption in
      households was estimated with a logistic regression model. RESULTS: Tobacco
      consumption during the first period was two times more likely from decile six (OR
      = 2.03, 95%, CI: 2.03-2.04) and during the second period from decile eight (OR =
      2.06, 95%, CI: 2.05-2.07). Households from decile one spent on average 9-22% of
      their income on tobacco; almost all of the households from decile ten spent only
      1% of their income on tobacco. CONCLUSIONS: Households with higher income
      consumed more tobacco than households with low income; nevertheless, households
      with the lowest income devoted a greater proportion of income to tobacco
      consumption.

PMID- 12055750
TI  - [Trends of tobacco demand in Mexico: 1992-1998].
AB  - OBJECTIVE: This paper aims at describing the behavior of tobacco's demand in
      Mexico across four one-year periods: 1992, 1994, 1996, and 1998, as well as to
      estimate a cigarette demand function. MATERIAL AND METHODS: A cross-sectional
      study with longitudinal analysis was conducted. Information sources were the
      Encuesta Nacional de Ingreso y Gasto de los Hogares (ENIGH) (National Survey of
      Household Income and Spending) (NHSIS) and the tobacco pack prices reported by
      the Procuraduria Federal del Consumidor (Profeco) (Federal Office of Consumer's
      Protection) (FOCP). Spending, income, and prices were deflated to 1994 prices;
      the population was stratified into quintiles of real income, by rural and urban
      areas. Indicators of daily consumption of cigarettes and packs were constructed
      and prices per pack calculated. Adjusted prevalence figures were estimated.
      Logistic and linear regression models were used for statistical inference; a
      cigarette demand function was estimated using multivariate logistic regression,
      to find socioeconomic determinants of cigarette consumption. RESULTS: The
      adjusted prevalence of household tobacco spending fell from 22.4 to 9.9% between
      1992 and 1998. Households allocated more than 4% of their income to tobacco
      consumption. A trend between income level and cigarette spending was observed,
      with the first quintile (the poorest population) allocated a greater share of
      their income than higher quintiles. The average daily consumption of cigarettes
      increased from 7.5 to 9.8 between 1992 and 1998. It was estimated that 90% of
      "smoker homes" consumed up to one package per day. The proportion of non-filter
      cigarettes increased from 0.4 to 4.8% between 1992-1998, with a bigger increase
      in 1996. Finally, it was found that the most important determinants of spending
      were prices and income. CONCLUSIONS: Policies focusing on tobacco prices would
      help to reduce tobacco consumption and improve the health of the Mexican
      population.

PMID- 12055751
TI  - [Educational methods in the prevention of smoking, among students of the
      Department of Herault, France].
AB  - OBJECTIVE: To evaluate the efficacy of two educational strategies to prevent
      tobacco addiction in schoolchildren living in Herault, France. MATERIAL AND
      METHODS: A study was conducted to deliver an intervention and make a concurrent
      comparison, among elementary school, fifth-grade students, during school years
      1992 to 1995, in Herault Department, Montpellier, France. Three observation
      groups were included: Group 1 was subject to a cross-sectional educational
      intervention; Group 2 was only subject to a single health activity on World Day
      Against Smoking; and Group 3 or control was not subject to any intervention.
      RESULTS: The prognostic role of peers and the family setting on tobacco
      consumption was confirmed; after three years, the Group subject to the sustained
      cross-sectional intervention showed a prevalence of smokers significantly lower
      than that of the other two groups. CONCLUSIONS: Even though tobacco consumption
      seems to begin earlier in boys than in girls, in the former the prevalence
      increases from 0.7 to 7% after three years. Preventive educational interventions
      should be maintained and reinforced to be effective on the initiation and
      cessation of tobacco smoking among children.

PMID- 12055752
TI  - [Role of atrial stimulation in the treatment of paroxysmal atrial fibrillation].
AB  - Preventive treatments for atrial fibrillation by stimulation have been developed
      for several years now, mainly due to the relative failure of anti-arrhythmic
      treatments. They are based on the hypothetical effects of stimulation by
      controlling cardiac frequency, abolishing bradycardia-dependent extrasystoles, by
      the inhibition of atrial automatic foci with "overdrive", and by the modification
      of intra- or inter-atrial conduction delays as well as by remodelling the
      arrhythmogenic substrate. It is clear that an undeniable effect exists for the
      prevention of atrial fibrillation, even for the risk of cerebral vascular
      accident, by physiological stimulation (DDD/DDDR) compared to pure ventricular
      stimulation (VVI/VVIR) in a heterogenous global population of stimulated
      patients. For the moment, there is not sufficient proof of a positive effect for
      the emerging sites of cardiac stimulation, either atrial mono-site or double site
      in the populations at high risk of atrial fibrillation, with or without
      associated bradycardia. Some new prevention algorithms by "overdrive" are under
      development but for the moment only a few preliminary studies seem to show a
      slight benefit. It is clear that at present stimulation should be reserved only
      for cases of atrial fibrillation associated with a classic indication for
      implantation. In these patients it is recommended to position the probes in an
      optimal manner in order to counteract conduction disorders, choosing an adapted
      double chamber stimulator with prevention algorithms. That said, the patient
      should be clearly warned that the long term success rate is no more than 50%.

PMID- 12055753
TI  - [Role of radiofrequency ablation in atrial fibrillation].
AB  - Atrial fibrillation is the most frequently encountered arrhythmia in the human
      species. Its danger is widely appreciated but it remains for certain patients and
      their practitioners an awkward or even exasperating problem. Only surgery and
      radiofrequency ablation allow certain patients to be cured. The surgical approach
      is of course warranted in the case of an otherwise necessary cardiac
      intervention. In the absence of a surgical indication, endovenous ablation, which
      is less aggressive, is preferred. The procedure consists of disconnecting the
      pulmonary veins which "house" 80 to 95% of the foci, together with the ablation
      of further non-venous foci, which are always difficult to treat. Side effects in
      experimental centres are rare and 70% of patients are cured, which allows
      cessation of antiarrhythmic and anticoagulant treatments. The procedure is
      currently offered to symptomatic patients having had at least one episode every
      ten days in spite of antiarrhythmics.

PMID- 12055754
TI  - [Endocavitary ablation for arrhythmias. New modalities of radiofrequency
      applications. New energy types].
AB  - Radiofrequency remains the reference energy type for catheter ablation of rhythm
      disorders. In the classic indications, which are atrial flutter or tachycardia,
      nodal re-entry and Wolff-Parkinson-White syndrome, this energy source has the
      best cost-efficiency-safety ratio, subject to strict conditions of use. Some new
      modalities of application have further improved performance, especially active
      irrigation of the electrode which allows induction of deeper lesions which is
      very useful for the ablation of difficult atrial flutters, epicardial fascicles
      of Kent and ischaemic ventricular tachycardias. The only emerging alternative
      energy type, in the framework of classical ablation, is cold, for which the
      principal advantages are the homogenous and slightly thrombogenic character for
      the lesion involved, and the possibility of reversible applications tests which
      are especially useful in the ablation of structures at risk. The situation is
      more open-ended concerning research on ablation for atrial fibrillation or the so
      called new energy types, such as ultrasound and laser, whilst recognising a
      renewal in interest, especially for circumferential ablation of the pulmonary
      veins to isolate the ectopic venous foci. Mechanical energy such as luminous
      energy is emitted across a catheter balloon deployed at the orifice of the vein,
      perpendicular to its axis, aiming to reach a continuous circumferential lesion
      with a minimum of applications. Equally radiofrequency has been undergoing
      significant evolution for this application, such as by the development of porous
      catheter balloons with a liquid electrode, as well as by the development of
      deployable circumferential catheters. Ablation is use for atrial fibrillation, by
      endocavity atrial segmentation remains a field of research in which
      radiofrequency retains an important place. It is delivered via multi-electrode
      catheters according to the new application modalities, either pulsed or by phase
      interval, which secure better efficacy by better continuity of the line of block.
      Research is equally underway on the use of microwaves and cold in this
      application.

PMID- 12055755
TI  - [Parasystole].
AB  - Parasystole is usually an extrasystolic rhythm which can occur at every level,
      but particularly in the ventricle. It is admitted that the parasystolic focus is
      protected from the environing myocardium by an entry block but can manifest
      itself. Actually, a pure unidirectional block does not exist and the environing
      myocardium affects the parasystolic rhythm by an electrotonic current which
      modulates the output. A non-parasystolic complex which occurs prematurely in the
      parasystolic cycle delays it. Conversely it accelerates the cycle when it occurs
      late. By this fact, a parasystole pacing is possible and can lead to a fixed
      coupling. This arrhythmia is frequently unknown and can be experimentally,
      reproduced by a sucrose gap preparation.

PMID- 12055756
TI  - [Nodal conduction].
AB  - The existence of a single atrio-ventricular fascicle had been suggested in the
      19th century by Wilhelm His junior. In 1906, Sunao Tawara described in details
      the existence of a specific muscular fascicle in charge of the atrio-ventricular
      conduction. Since, it has remained famous under the name of atrio-ventricular
      node. It is located in the apical part of the Koch triangle. It is 5 to 7 mm long
      and 2 to 5 mm wide and includes often an enlargement of its compact portion along
      the fibrous annulus to the coronary sinus ostium which seems to be associated
      with the development of a intra- or atrio-nodal re-entry circuit. Its action
      potentials are qualified as "slow response" and propagate with a speed of 0.02 to
      0.05 m/sec (which is comparable to that present in the sinus node). This
      propagation slowness explains the PR interval on surface EKG tracings and the AH
      interval in intra-cardiac electrogram. When AV node cells are requested by a
      rapid atrial rhythm, their physiological response is made under the mode of
      beatings group described by Luigi Luciani and Karel Wenckebach, prior to the
      EKG's invention. The atrio-ventricular physiological relationship during the
      atrial acceleration is made according to the Luciani-Wenckebach mode and then 2/1
      mode as described in the non-linear dynamics theory. The most frequent
      pathological of the nodal conduction are the atrio-ventricular blocks and nodal
      duality. They are described and commented in this article. The nodal conduction
      disturbances are currently accessible to different therapeutic patterns such as
      cardiac pacing or ablative techniques. Nonetheless the innermost mechanism are
      still incompletely identified and will for sure be a matter of numerous studies
      in the future.

PMID- 12055757
TI  - [Diagnostic use of adenosine triphosphate in cardiac arrhythmias].
AB  - Adenosine triphosphate (ATP) has been used for more than 50 years as a major
      medication in our therapeutic arsenal for the termination of supraventricular
      tachycardia crises for which the mechanism is re-entry implicating the
      atrioventricular node. In the present article other applications of ATP as a
      diagnostic agent for several cardiac arrhythmias are described: differential
      diagnosis of narrow or wide QRS tachycardia, diagnosis of a latent accessory
      pathway (intermittent or hidden), diagnosis of intranodal duality, and non
      invasive evaluation of the results of the ablation of the slow pathway, and
      finally non-invasive diagnosis of the tachycardia mechanism in patients with
      palpitations or tachycardia with an obscure mechanism.

PMID- 12055758
TI  - [Monophasic action potentials: considerations and limits].
AB  - Monophasic action potentials are currents recorded in vivo in the extracellular
      milieu which can reproduce the repolarisation signal of intracellular action
      potentials. For a long time unstable and complex to record, they now require
      simply a firm myocardial contact with a bipolar electrophysiological catheter and
      modification with recording filters, without a high-pass filter (DC). They have
      been widely used in recent years to study in vivo modifications of the action
      potential durations with frequency, epi-, endo-, or intramyocardial cellular
      topography, endocavity pressure modifications, or antiarrhythmic medication. They
      allow a unique means of continuous analysis in animals or in patients of the
      action potentials during polymorphic arrhythmias such as atrial fibrillation,
      ventricular fibrillation and torsades de pointes, although in these cases the
      refractory periods can not be measured precisely and continuously, beat after
      beat. In contrast, their clinical or experimental use in the study of arrhythmias
      dependent on premature post-depolarisations has without doubt been excessive and
      disputable, because it appears improbable that authentic premature post
      depolarisations could ever be obtained on a monophasic action potential, which
      always represents the summation of the action potentials of dozens of cells.

PMID- 12055760
TI  - [Prevalence of cardiovascular risk factors].

PMID- 12055759
TI  - [Role of antiarrhythmics in the treatment of paroxysmal atrial fibrillation].
AB  - Atrial fibrillation is not a homogenous entity. Numerous parameters affect its
      cause, its continuation, and the arrest of an attack. The presence or absence of
      cardiopathy and left ventricular dysfunction play a major role via the
      electrophysiological and haemodynamic consequences and the repercussions on the
      state of the autonomic nervous system, and finally on the effect of anti
      arrhythmics themselves. This shows the importance of taking into account all of
      these parameters together in order to adapt the therapeutic approach. Equally,
      this underlines the difficulty in interpreting clinical studies comparing
      pharmacological treatments when the populations treated are poorly defined or
      very heterogenous. Most often, one drug is not more or less effective than
      another, it is more or less suited to the patients treated. The frequency of
      recurrences of AF despite anti-arrhythmic treatment (on average 50% to 60% at one
      year) means that in paroxysmal AF the goal of anti-arrhythmic treatment is
      relatively modest: essentially reducing the frequency, duration and severity of
      AF attacks, allowing an improvement in the quality of life. The consequences in
      daily practice are clear: one must ensure good patient compliance and minimise
      the risks of treatment: side effects of and pro-arrhythmic effects of anti
      arrhythmics.

PMID- 12055761
TI  - [Cardiovascular risk factors in France. Prevalence and association].
AB  - The object of this study was to assess the prevalence of modifiable
      cardiovascular risk factors and their association in 61,108 subjects over 15
      years of age who volunteered for a systematic medical check-up, free of charge,
      and performed in a health centre in central France. The risk factors were defined
      as follows: hypertension, diabetes, hypercholesterolaemia, hypertriglyceridaemia:
      medical treatment or value above the upper limits of normal defined by national
      or international recommendations. obesity and android fat distribution as defined
      by the principal recommendations. The commonest risk factor was
      hypercholesterolaemia (60% of men and 64% of women) followed by android obesity.
      The prevalence of hypertension was greater in men than in women (44 vs 33%).
      Twenty eight per cent of men and 17% of women admitted to smoking. The percentage
      of smokers was higher in people under 30. Diabetes was observed in 3% of men and
      2% of women. The association of risk factors was observed at an older age in
      women than in men. The association of 3 risk factors was four times greater in
      men than in women in the whole population. In conclusion, this study shows that
      cardiovascular risk factors are very common in persons undergoing a medical check
      up and that these factors are often associated at an earlier age in men than in
      women.

PMID- 12055762
TI  - [Raynaud phenomenon and wine growing].
AB  - OBJECTIVES: It has been hypothesised that Raynaud's phenomenon (RP) may have a
      multifactorial aetiology involving potential causal or triggering factors which
      can be found in the workplace. The objective of the study was to identify
      prevalence of RP and occupational risk factors in a population of wine growers.
      METHODS: The survey was carried out in 1997-1998 in Champagne county area and
      included all self-willed wine growers. They were compared to populations of
      farmers, industrial workers and employees. Data were collected at the annual
      visit of the occupational health physician. RP was identified from a list of
      symptoms occurring from exposure to cold. The role of different potential risk
      factors was studied. RESULTS: 405 wine growers and 374 controls were included in
      the study. The prevalence of RP was significantly higher in the wine growers
      groups (9.8%) compared to controls group (2.9%). The prevalence of RP in female
      wine growers or concerning exposure to vibrations were not significantly
      different from these, found in control group. Smoking consumption was higher and
      cold exposure was longer in wine grower with RP compared to controls with RP.
      CONCLUSION: The study confirms the strong prevalence of RP in wine growers of
      Champagne country area. Climatic factor like cold exposure could play a possible
      part.

PMID- 12055763
TI  - [Medium-term results of multisite biventricular stimulation in severe cardiac
      failure].
AB  - Since its introduction in cardiac failure in 1994, biventricular cardiac
      stimulation has been widely applied with many clinical trials and the development
      of new specific technology. The authors present the results observed in the first
      125 consecutively implanted patients at the Rennes University Hospital. After a
      mean follow-up of 22 months, the mortality rate was 40%. The causes of death were
      sudden death in 42% of patients, progression of cardiac failure in 34% and non
      cardiac in 24%. The functional benefits of biventricular cardiac stimulation were
      seen through significant improvement in HYHA Class, 3.3 +/- 0.5 before
      implantation to 2.3 +/- 0.8 at the end of follow-up, and by a significant
      increase of 40% of peak VO2 and of maximal duration of exercise. With the
      learning curve and development of new technology, the left ventricular
      catheterisation via a coronary sinus vein, increased from 56% to over 95% during
      the last two years with an acceptable rate of complications. These results, with
      the reserve of not being a controlled trial, show the feasibility, safety and
      efficacy of biventricular cardiac stimulation in terms of functional benefit.
      Clinical trials are currently underway to assess the impact of this method on
      morbi-mortality and to assess the concept in association with ventricular
      defibrillation.

PMID- 12055764
TI  - [Value of pulsed Doppler tissue imaging for early detection of myocardial
      dysfunction with anthracyclines].
AB  - The cumulative and definitive nature of chronic cardiotoxicity of anthracyclines
      requires a preventive strategy of early diagnosis. The authors undertook a
      prospective study of the association of echocardiography, mitral Doppler and
      pulsed Doppler tissue imaging of the left ventricular lateral and posterior walls
      in the context of this problem in 20 patients without cardiac disease undergoing
      cancer chemotherapy including anthracyclines. Doppler echocardiography was
      performed before the first session of chemotherapy and at the end of treatment, 6
      +/- 4 months later. After a total cumulative dose of 227 +/- 91 mg/m2 of
      doxorubicine, there were no changes in left ventricular ejection fraction but a
      significant decrease in mitral E wave velocity (p = 0.04) and in E/A ratio (p =
      0.01), suggesting early changes in left ventricular relaxation. The Doppler
      tissue examination confirmed the presence of radial and longitudinal
      abnormalities in myocardial relaxation (decreases in myocardial E wave velocities
      of the posterior and lateral walls of the left ventricle, p = 0.02 and p = 0.01,
      respectively). The peak velocity of the myocardial systolic wave (Sm) was
      significantly decreased in the lateral wall (p = 0.02) and approached statistical
      significance in the posterior wall (p = 0.07). These results suggest concomitant
      changes in myocardial systolic and diastolic function with moderate doses of
      anthracyclines. Therefore, pulsed Doppler tissue examination enables earlier
      detection of left ventricular cardiotoxicity with anthracyclines than classical
      echocardiographic parameters.

PMID- 12055765
TI  - [One center's experience of coronary angioplasty with a 5 French catheter guide
      by a femoral approach at the same time as coronary angiography].
AB  - The object of this study was to assess the feasibility of so-called ad hoc 5 F
      percutaneous transluminal coronary angioplasty (PTCA). This monocentric register
      included 200 consecutive procedures (233 lesions) of 5F PTCA by a femoral
      approach after a bolus of standard heparin (50 to 70 IU/kg). The population
      included 15.4% of stable angina, 29.4% of unstable angina, 11% acute phase, 13.5%
      post-revascularisation angina and 30.7% post-infarction cases. A successful
      procedure was defined as a good angiographic result without ischaemic
      complications. A failed 5F procedure was defined by the need to fall back on a 6F
      PTCA. The peripheral vascular complications were recorded. The lesions were
      stented in 77.4% of cases including 13.4% of direct stenting. There were 200
      successful procedures (87%). The failures (N = 26) were mainly explained by the
      inability to cross chronic obstruction (N = 11). The ischaemic complications
      included 2 coronary bypasses (2 retrograde dissections of the left anterior
      descending artery) and 7 enzymatic increases without ECG changes. Fall back to 6F
      PTCA was required in 4 cases (1.7%) always because of the instability of the 5F
      catheter guide before the procedure. The quality of coronary contrast was
      estimated to be good. The vascular complication rate was low with 2% of
      communicating haematomas (N = 4). Therefore, 5F PTCA is feasible with failure and
      complication rates comparable to those reported with catheters of larger
      dimensions. One of its principal advantages is "ad hoc" angioplasty after 5F
      coronary angiography.

PMID- 12055767
TI  - [Open heart radio frequency left atrial compartmentation during mitral valve
      surgery: an alternative to the labyrinth procedure?].
AB  - The authors report their experience of radiofrequency left atrial
      compartimentation during open heart mitral valve surgery on 37 patients with a 42
      +/- 12 months history of atrial fibrillation. The preoperative left ventricular
      ejection fraction was 62 +/- 8%; the left atrial diameter was 59 +/- 11 mm. The
      mean operative time was 245 +/- 60 minutes, which included 19 +/- 5 minutes for
      the ablation procedure. There were 2 early postoperative deaths and 2 deaths from
      non-cardiac causes at 3 and 6 months. The left ventricular ejection fraction and
      left atrial dimension were significantly decreased at the time of hospital
      discharge (54 +/- 12% and 51 +/- 7 mm respectively) (p < 0.01). After an average
      follow-up of 1 year, 81% of patients were free of atrial fibrillation: 6 patients
      had undergone DC cardioversion and 1 had a dual-chamber pacemaker. Patients in
      sinus rhythm after the ablation were associated with shorter periods of atrial
      fibrillation and smaller left atrial dimensions postoperatively than those who
      remained in fibrillation. The authors conclude that radiofrequency
      compartimentation of the left atrium associated with antiarrhythmic therapy can
      interrupt atrial fibrillation in 81% of patients at 1 year: the ablation
      procedure takes only 8% of the operation time. Predictive factors of success of
      ablation should be defined to determine which patients benefit most from this
      technique.

PMID- 12055766
TI  - [Medical cost of cardiovascular risk factors prevention in France].
AB  - AIM: To assess the cost of the preventive measures against hypertension and
      dyslipidemia in French subjects aged 35-64 years. METHODS: Cross-sectional study
      conducted in 433 men and 424 women from the three French centres participating in
      the WHO-MONICA Project and receiving antihypertensive and/or hypolipidemic drug
      therapy. RESULTS: In both genders, beta-blockers and ACE inhibitors were the most
      frequently prescribed antihypertensive drugs, and half of treated hypertensive
      subjects still had blood pressure levels beyond the normal limits, this
      percentage being lower in men and in Bas-Rhin. Daily cost of antihypertensive
      treatment ranged between 0.58 (minimum) and 1.72 [symbol: see text] (maximum) in
      men and between 0.54 and 1.46 [symbol: see text] in women, with no differences
      between centers. Fibrates were the most frequently prescribed hypolipidemic drug,
      and daily cost of treatment ranged between 0.33 and 1.33 [symbol: see text] in
      men and between 0.36 and 1.26 [symbol: see text] in women; in men, costs were
      lower in the Communaute Urbaine de Lille. Slightly more than half of the
      hyperlipidemic subjects had their LDL levels within normal values; no differences
      were found between centers or genders. Finally, the daily cost of "therapeutic
      inefficiency" for hypertension and dyslipidemia for age group 35-64 years in
      France was estimated to be over one million [symbol: see text]. CONCLUSION: The
      cost of the antihypertensive and hypolipidemic drug treatment is high and efforts
      should be undertaken in order to increase the efficiency of prevention.

PMID- 12055768
TI  - [Pregnancy and dilated or hypertrophic cardiomyopathies].
AB  - The risk of pregnancy in women with hypertrophic (HCM) or dilated (DCM)
      cardiomyopathy may be difficult to assess. Haemodynamic changes occur during
      pregnancy which may destabilize the underlying cardiac disease. Nevertheless,
      with or without pharmacological support and with vigilance at the time of
      childbirth, the outcome of pregnancies in patients with HCM is usually good
      without extra-mortality. On the other hand, complications often occur in
      symptomatic patients with DCM and left ventricular dysfunction. Pregnancy is not
      advisable in this group of patients. Finally, pregnancy may be responsible for a
      specific type of cardiomyopathy, peripartum cardiomyopathy, a rare condition
      occurring in the last month or during the 5 following months, which has an
      unpredictable outcome to complete recovery, myocardial sequellae or aggravation
      leading to cardiac transplantation or death. These patients are at high risk in
      future pregnancies.

PMID- 12055770
TI  - [Cardiovascular physiology: recent findings].
AB  - The practice, research and teaching of biology have changed considerably over the
      last few years, largely due to the sequencing of all of the human genome. These
      changes are of interest to both the researcher and clinician, the physician and
      surgeon. They involve the tools, genetic transfers and transgenic technology,
      global methods of analysis of genetic expressions directly generated by the
      genome programme and computerisation. Several major concepts have evolved:
      transgenic physiology or reverse physiology which allows study of all functions,
      especially cardiac, and their determining factors; functional and physiological
      genomics which allow the study of all changes of genic expression, in cardiac
      failure for example; physiological convergences in genetics which underline the
      increasing importance of the physiologist in genetics; pharmacogenetics finally,
      the genetics which allow better choice of treatment for each individual.

PMID- 12055769
TI  - [Heart failure and respiratory sleep disorders].
AB  - Chronic cardiac failure is often associated with sleep respiratory disorders.
      These abnormalities are often unrecognised and represent a marker of the severity
      of cardiac failure and carry a poor prognosis. The mechanism of apnoea is either
      central, resulting in periodic nocturnal Cheyne-Stokes respiration, or peripheral
      by obstruction of the upper respiratory tract. Both mechanisms may be observed in
      the same patient. Oxygen desaturation, fragmentation of sleep and inspiratory
      depression lead to sympathetic activation and an increase in let ventricular
      afterload which can aggravate the cardiac failure. Treatment by continuous
      positive pressure with a nasal mask can help some patients. It is therefore
      important to diagnoses these nocturnal disorders using simplified
      polysomnographic recordings.

PMID- 12055771
TI  - [Fulminating myocarditis: myocardial recovery after circulatory assistance].
AB  - The clinical expression of acute myocarditis is variable from paucisymptomatic to
      fulminating forms which are usually lethal within days. The latter presentation
      takes the form of very acute cardiac failure. During this phase, the severity of
      myocardial dysfunction may be such that death ensues. However, if the patient
      survives, paradoxically, these forms have a better long-term prognosis with
      complete recovery of myocardial function being possible after the acute phase.
      The authors report a typical case of fulminating myocarditis with
      electromechanical dissociation, which recovered completely after a period of
      circulatory assistance. This case illustrates the rapidity of deterioration of
      the haemodynamic status and the importance of organ dysfunction despite early
      management. In a review of the literature, the authors found about 150 reported
      cases of acute myocarditis treated with circulatory assistance. In the best
      series, about half the patients were weaned off the circulatory assistance
      without having to undergo cardiac transplantation. However, the potential
      recovery of myocardial function is difficult to predict.

PMID- 12055772
TI  - [Renovaascular hypertension and Von Recklinghausen neurofibromatosis].
AB  - This clinical case illustrates the diagnosis of a secondary cause of hypertension
      in a patient with Von Recklinghausen's disease. The hypertension resulted from a
      complex malformation of the right renal artery and dysplasic stenosis of the left
      inferior polar artery treated successfully by simple angioplasty. This case
      illustrates the high proportion of vascular (renal artery dysplasia, coarctation
      of the aorta) and endocrine (pheochromocytoma) causes of hypertension in patients
      with neurofibromatosis.

PMID- 12055773
TI  - Negative social perception of hypothetical workers with rheumatoid arthritis.
AB  - In the present study, 340 college subjects evaluated the job performance of
      hypothetical workers of varying health status, to test the hypothesis that
      workers with rheumatoid arthritis (RA) are more negatively perceived than other
      workers (paraplegic, healthy) despite equivalence in age, sex, education, job
      history, and time off from work for medical reasons. Results indicated that
      workers with RA are perceived as having significantly poorer interpersonal job
      skills and are deserving of significantly poorer scores for overall job
      performance, although no differences were obtained in the ratings of their job
      commitment or job expertise. The suggestion is made that an unfavorable social
      reaction to RA patients in the workplace is one factor that impairs the
      development of social support for these patients at work and contributes to their
      inflated disability rate.

PMID- 12055774
TI  - Do optimism and pessimism predict physical functioning?
AB  - Dispositional optimism has been shown to be related to self-report measures of
      health and well-being, yet little research has examined the relationship between
      optimism and more objective measures of functioning. The purpose of this study
      was to examine the relationship between optimism and pessimism and objective
      physical functioning. Four hundred eighty community-dwelling older adults with
      knee pain completed a measure of optimism and pessimism and were observed
      performing four daily activities (walking, lifting an object, climbing stairs,
      and getting into and out of a car). Results indicated that pessimism was
      significantly related to performance on all four tasks (p < .001), while optimism
      was related to performance only on the walking task (p < .05), after controlling
      for demographic and health variables.

PMID- 12055775
TI  - Examining the role of social support and group cohesion in exercise compliance.
AB  - The present study sought to examine the role of social support and group cohesion
      in the compliance behavior of females required to exercise for health-related
      reasons. Compliance behavior was assessed as attendance and dropout behavior.
      Participants (N = 49) drawn from a clinical exercise group completed
      questionnaires to assess cohesion and social support. Discriminant function
      analyses were able to discriminate between high and low attenders as well as
      between dropouts and graduates. Participants reporting high scores on the support
      provision of reliable alliance and the cohesion factor of ATG-Task, along with
      low scores on the social support provision of guidance, were more likely to
      attend a higher proportion of classes. For dropouts, participants with higher
      scores on the support provision of reliable alliance were less likely to drop
      out. As a secondary objective, it was found that cohesion and social support
      variables both contributed to the successful prediction of attendance.

PMID- 12055776
TI  - The impact of disability and disease duration on social support of women with
      rheumatoid arthritis.
AB  - The objective was to investigate the impact of physical disability and disease
      duration on the amount of social support received by female patients with
      rheumatoid arthritis. Two hundred sixty-four patients were assessed in a cross
      sectional study. Disease duration had a negative relationship to daily emotional
      support; the length of disease duration was related to less emotional support. A
      combination of long disease duration and high disability was related to a low
      degree of problem-oriented emotional support. High physical disability was
      associated with less social companionship. Patients with high disability and few
      friends and patients with high disability and few neighbours reported less social
      companionship than patients with high disability and four or more friends or
      three or more neighbours. The combination high disability and few friends were
      associated with less problem-oriented instrumental support. Number of friends,
      age, and personality type all contributed to the variance in social support.

PMID- 12055777
TI  - Parental report of health-related quality of life in children with sickle cell
      disease.
AB  - Health-related quality of life (HRQOL) of youths with sickle cell disease (SCD)
      has not been described, despite the psychosocial and physical consequences
      associated with the disease. We compared the HRQOL of 58 children with SCD to a
      demographically similar sample of 120 healthy children and examined predictors of
      HRQOL. Child HRQOL was assessed using the Child Health Questionnaire--Parent
      Report Form. Review of medical charts of children with SCD provided data on
      disease-related complications. Results demonstrated that caregivers of children
      with SCD reported that their children had more limited physical, psychological,
      and social well-being than healthy children. Older child age, female gender, and
      more disease-related complications predicted limitations in the physical health
      of children with SCD. The findings indicated that SCD significantly affects the
      HRQOL of youths. Certain subgroups of patients (e.g., children with more disease
      complications) may benefit from interventions specifically designed to improve
      their physical functioning.

PMID- 12055778
TI  - Cynical hostility and the accuracy of decoding facial expressions of emotions.
AB  - To examine the relation between cynical hostility and the accuracy of decoding
      facial expressions of emotions, 101 young adult participants completed the Cook
      Medley Hostility Scale and Ekman's Pictures of Facial Affect. Results revealed
      that higher hostility scores were correlated with a greater number of errors in
      decoding facial expressions of emotions. Hostile individuals were more likely
      than nonhostile individuals to label inaccurately facial expressions of "disgust"
      as being "anger" and of "happiness" as being "neutral." Results also revealed
      that males were more likely than females to label incorrectly facial expressions
      of disgust as anger. Partial correlations, controlling for gender, revealed that
      the relation between hostility and inaccurate perceptions of facial portrayals of
      happiness was significant, whereas the relation between hostility and inaccurate
      perceptions of facial displays of disgust was no longer significant.

PMID- 12055779
TI  - The longitudinal influence of peers on the development of alcohol use in late
      adolescence: a growth mixture analysis.
AB  - This study examines heterogeneity in the developmental trajectories of alcohol
      use in adolescents and the accompanying trajectory-specific longitudinal
      influence of exposure to their deviant peers. Using a national data set on
      alcohol use (N = 188), a growth mixture model capturing growth trajectories in
      adolescent alcohol use from ages 14 to 18 years was first examined. This was
      followed by an investigation of age-varying influences of peers on adolescent
      alcohol use and the co-development of peer influence and adolescent alcohol use.
      Results of growth mixture modeling of repeated-measures data on adolescent
      alcohol use showed two distinct latent classes of developmental trajectory with
      significant differences in levels of use. Analyses of exposure to deviant peer
      and adolescent alcohol use variables indicated differential effects of peers
      across trajectory classes. Stronger prospective influences for the trajectory
      group having a low initial status of use were found. Findings from this study
      suggest the need to consider heterogeneity in the study of peer influence on
      alcohol use during adolescence to facilitate more refined targeting of
      prevention/intervention programs.

PMID- 12055780
TI  - Primary immune disorders in children and their diagnosis.
AB  - The clinical features and laboratory findings of 18 children with various primary
      immune deficiencies and their immunologic diagnosis have been discussed. In 3
      patients of ataxia telangiectasis human foetal thymus transplantations have been
      performed with some success.

PMID- 12055781
TI  - Immunodiagnosis of amoebiasis.
AB  - Serological studies were done on 127 cases using three different techniques
      namely indirect haemagglutination (IHA), indirect fluorescent antibody test (IFT)
      and counter immunoelectrophoresis (CIEP) to detect antiamoebic antibodies. All
      amoebic liver abscess cases showed significant titre of antibodies by all the
      three tests used. In the group of patients suffering from amoebic pathology of
      liver, 90.47 per cent were positive by IHA, 100 per cent by IFT and 85.71 per
      cent by CIEP respectively. Among amoebic dysentry and amoebic colitis cases 81.81
      per cent and 80.64 per cent respectively were positive by IHA. The corresponding
      figures for IFT were 100 per cent and 74.19 per cent and for CIEP 90.90 per cent
      and 64.51 per cent respectively. Follow up study showed no significant fall in
      antibody titre in nine cases studied upto 10 weeks after treatment. Amoebic
      antigen could be detected in pus from all the nine cases with amoebic liver
      abscess by CIEP test.

PMID- 12055782
TI  - Immunodiagnosis of malaria.
AB  - Different approaches to immunodiagnosis of malaria in an endemic country have
      been described in this paper. Demonstration of circulating malaria antigen may be
      done by gel-diffusion and counter-immunoelectrophoresis. Parasite associated
      antigen may be demonstrated by highly sensitive methods like radio-immunoassay or
      enzyme linked immuno sorbent assay. Malaria antibodies of the IgG type being long
      lasting do not appear to have any role in immuno-diagnosis. However,
      determination of malaria specific IgM antibodies by P. gallinaceum
      haemagglutination test or IgM immunofluorescence test may be simple and useful in
      immunodiagnosis of malaria. The tests though evaluated in different laboratories
      may not be applicable in the field for diagnosis of malaria at the present
      moment. However, it is envisaged that with the availability of different
      specificities of monoclonal antibodies by way of hybridoma technology and also
      with the help of recombinant DNA techniques immunodiagnosis of malaria in the
      field situation may become a reality.

PMID- 12055783
TI  - Immunodiagnosis of bacterial meningitis.
AB  - The quest for the search of rapid, cheap, easy to perform and highly sensitive
      and specific tests has resulted into the introduction and application of various
      new tests for the diagnosis of bacterial meningitis. Most of these tests are
      based on immunological principles, viz. counter-immunoelectrophoresis, latex
      agglutination test, co-agglutination, radio-immunoassay, haemagglutination
      inhibition as well as study of immune profile of cerebrospinal fluid. Apart from
      these certain non-immunological tests viz. Limulus amoebecyte lysate test, gas
      liquid chromatography, nitroblue tetrazolium dye reduction test have also been
      evaluated to make the laboratory diagnosis of this important clinical entity
      rapid and more reliable. These tests have been discussed and their current status
      presented.

PMID- 12055784
TI  - Immunoprophylaxis in poliomyelitis.
AB  - While individual immunoprophylaxis requires an effective vaccine, disease control
      requires an effective strategy for the application of the vaccine. In India, the
      oral polio vaccine (OPV) is given to children from 3 months to 2 years of age, in
      a 3-dose schedule. This strategy has not resulted in a fall in disease incidence
      in any community. It is suggested that two factors are responsible for the poor
      performance of OPV. First is a geographic variation in the response of infants to
      OPV, which result in only 80 per cent effective immunisation after 3 doses. The
      second factor is related to the age at which immunisation will achieve maximum
      benefit. Since the rate of natural poliovirus infection is highest during 6-18
      months of age, immunisation should be completed by 6 months of age for disease
      control. If this is not feasible, an alternate strategy is necessary. It is
      suggested that pulse immunization in geographic units of population is a suitable
      method to control poliomyelitis.

PMID- 12055785
TI  - Immunoprophylaxis against rabies.
AB  - Rabies is responsible for a large extent of morbidity and mortality in human
      beings. However, the long incubation period of the disease allows the effective
      utilization of post exposure immunization. Till recently neural tissue vaccines
      were the mainstay of antirabic immunoprophylaxis. These vaccines are, associated
      with severe neuroparalytic complications. The recent introduction of human
      diploid cell vaccine and chick embro fibroblast vaccines have heralded a new era
      in antirabic vaccination because of their high immunogenicity and lack of major
      side effects.

PMID- 12055786
TI  - Immunoprophylaxis in tuberculosis.
AB  - In the Chingelput trial of immunoprophylaxis against tuberculosis, BCG
      vaccination did not protect against pulmonary especially bacillary tuberculosis
      commonly known 'adult form' of tuberculosis. The study however, did not answer
      the question whether BCG vaccination offers protection against 'childhood forms
      of tuberculosis' or not. However, notwithstanding these results, the study has
      generated some new ideas and has opened vast areas for future research. The
      results of new projects will be awaited keenly. The current situation is
      discussed here.

PMID- 12055787
TI  - Immunodiagnosis in clinical practice.
AB  - Although the definitive diagnosis of diseases caused by worms and protozoa
      depends upon the demonstration of adult parasite or its ovum in excreta, blood
      and tissue biopsies of the patient, immunological methods can be of help in the
      identification of associated immunological syndromes, pathogeneses of these
      infections in man and as a guide to therapy. However, the non-availability of
      pure antigens is a limiting factor in effective application of these tests. The
      present paper describes the immunological syndromes associated with these
      diseases as well as some of the in-use immunodiagnostic tests.

PMID- 12055789
TI  - Clinical trials in healthy volunteers with the new purified chick embryo cell
      rabies vaccine for man.
AB  - Behringwerke has developed the new, safe and economical purified chick embryo
      cell (PCEC) rabies vaccine. Due to the purification by zonal centrifugation the
      compatibility of this vaccine is excellent. Among 933 vaccinations in 219 healthy
      volunteers the only side-effect was mild pain at the injection-site in 17
      vaccinations (1.7 per cent). The sero-conversion of PCEC rabies vaccine was 100
      per cent in the tested healthy volunteers. The kinetics of antibody induction
      after PCEC rabies vaccine is comparable to antibody induction after HDC rabies
      vaccine. PCEC rabies vaccine induces cellular immunity as measured in lymphocyte
      transformation test, but no interferon activity.

PMID- 12055788
TI  - Immunoprophylaxis in pertussis.
AB  - Pertussis is one of the common paediatric infectious diseases and an important
      public health problem specially so in the developing countries. An effective
      vaccine against this disease is available and given along with diphtheria and
      tetanus toxoids. However, the association of systemic, especially the
      neurological, complications have made it a controversial agent. The preparation
      of vaccine, its complications and mechanism of production of complications are
      presented.

PMID- 12055790
TI  - Antibody response to human diploid cell antirabies vaccine in human volunteers--a
      preliminary study.
AB  - HDCS was given to 12 healthy volunteers in three different schedules. The levels
      of neutralising antibodies were determined by ELISA test. The antibodies could be
      detected on day 7 after vaccination. With 3 doses (D-0, D-15, D-30) satisfactory
      high level of neutralising antibodies could be detected in 3 out of 4 volunteers
      till 2 years. With 2 doses (D-0, D-15) similar levels could be observed only till
      day 270, and with single dose significant levels could be seen till day 30 only
      after which levels declined and no antibodies could be detected on day 270.
      Reactogenicity of the vaccine was nil as no major or minor side-effects were
      observed in any of the volunteer.

PMID- 12055792
TI  - In vitro cultivation of infective larvae of Dirofilaria immitis.
AB  - Infective larvae (L3) of Dirofilaria immitis were cultivated in various synthetic
      media. L3 obtained from Aedes aegypti mosquitoes by mass dissection were
      inoculated into the media, viz: RPMI 1640 medium with 10 per cent human AB serum
      (medium-A); Tc-199 medium with organic acids, sugars of Grace's insect medium and
      10 per cent foetal calf serum (FCS) (medium-B); and Grace's insect medium with 10
      per cent FCS (medium-C). Maximum survival of 26 days was found in medium 'A'.
      Approximately 80 per cent healthy larvae moulted after 72 hours. They increased
      in size from an initial average length of 1050 microns and 25 microns width to an
      average 1600 microns length and 35 microns width. Blunting and rounding of
      anterior ends were conspicuous.

PMID- 12055791
TI  - Cellulose acetate precipitation test in sero-diagnosis of amoebiasis.
AB  - Cellulose acetate precipitation (CAP) test for the detection of antibody against
      Entamoeba histolytica using the axenic antigen, was performed on the 127 serum
      samples obtained from patients with amoebic liver abscess (14), amoebic hepatitis
      (21), amoebic dysentry (11), amoebic colitis (31), other parasitic infestations
      (25) and normal individuals (25). The percent positivity was 100, 95.23, 90.9,
      67.74 and 16 and 12 respectively whereas the corresponding figures for the
      indirect immunoflourescence (IFAT) test were 100, 100, 100, 74.19, 12 and 8
      respectively. Although CAP is not as good a test as IFAT, yet it can be
      recommended for routine testing due to its sensitivity, speed of performance and
      applicability to a single serum sample.

PMID- 12055793
TI  - Comparative evaluation of microtitre and tube agglutination technique for
      serodiagnosis of enteric fever.

PMID- 12055794
TI  - Short-range attractiveness of pregnant women to Anopheles gambiae mosquitoes.
AB  - Malaria is a major cause of illness and an indirect cause of mortality in
      pregnant women. It can also cause stillbirths and low-birthweight babies. We have
      shown previously that pregnant women attracted twice as many Anopheles gambiae
      mosquitoes, the principal African malaria vector, as their non-pregnant
      counterparts over distances of about 15 m. In the current study (in 1998/99) we
      compared the short-range attractiveness of both pregnant and non-pregnant women
      sleeping under untreated bednets in Gambian villages. First, we measured the rate
      of mosquito entry under bednets and, second, we calculated the proportion of
      mosquitoes biting mothers under each bednet compared to their children. The
      feeding preference of An. gambiae collected under nets was determined by DNA
      fingerprinting blood samples from human subjects sleeping under each bednet and
      comparing these to fingerprints obtained from mosquito bloodmeals. Pregnant women
      were more attractive to An. gambiae mosquitoes than non-pregnant women under an
      untreated bednet. The number of mosquitoes entering bednets each night was 1.7
      4.5 times higher in the pregnant group (P = 0.02) and pregnant women also
      received a higher proportion of bites under the bednets than did non-pregnant
      women (70% vs 52%, P = 0.001). This study clearly demonstrates that pregnant
      women are more exposed to malaria parasites than other women, which contributes
      to the greater vulnerability of pregnant women to malaria.

PMID- 12055795
TI  - Enhanced sandfly attraction to Leishmania-infected hosts.
AB  - We report that hamsters infected with Leishmania infantum are more attractive to
      female sandflies in bioassays. Entrained odours from infected animals were shown
      by gas chromatography to contain peaks absent from uninfected individuals.
      Implications of enhanced transmission, potential for developing novel diagnoses
      and the significance to epidemiological models are discussed.

PMID- 12055796
TI  - Cyst production and transmission of Entamoeba and Endolimax.
AB  - We studied the cyst production of 340 asymptomatic carriers with single or mixed
      infections of Entamoeba histolytica/Entamoeba dispar, Endolimax nana and
      Entamoeba coli. It was found that the main source of transmission was a small
      group of 37 (10.9%) carriers who produced 70.2% of all cysts. Gender was an
      important factor for cyst production of Ent. histolytica/Ent. dispar, since males
      produced 6-fold more cysts than females. Females produced 'large' (13-15 microns)
      Ent. histolytica/Ent. dispar cysts and males small (10-12 microns) cysts when
      concentration was > 2000 cysts/g. When concentration was < 2000 cysts/g, cysts
      were the same size for both sexes (11.6 +/- 0.3 microns). In Ent. coli
      infections, an inverse relationship between the number and size of cyst was found
      for both sexes. Cysts of End. nana were not affected by gender or cyst
      concentration. Following cyst production by a carrier infected with Ent. coli and
      Ent. histolytica for 28 days, we identified synchronized cycles of cyst
      production for both species. Altogether, these data suggest that cyst-mediated
      transmission is a highly regulated process in which synchronization among
      different species and gender of the host have an important role in transmission.

PMID- 12055797
TI  - The emerging epidemic of echinococcosis in Kazakhstan.
AB  - Since independence from the Soviet Union in 1991 the annual surgical incidence of
      cystic echinococcosis in Kazakhstan has increased from 1.4 cases/100,000 in 1991
      to 5.9 cases/100,000 in 2000. In some regions the annual surgical incidence is
      now over 10 cases/100,000. Twenty-nine percent of recorded cases in 2000 were in
      children aged < 14 years, which indicates recent transmission. Most of the cases
      are occurring in the regions where the sheep industry is concentrated, indicating
      that the zoonotic sheep strain of Echinococcus granulosus is the likely cause of
      the problem. The gross domestic product (GDP) of Kazakhstan has declined by
      nearly 50% since independence. Concurrently there has been decreased health
      spending with decreases in the numbers of hospitals, hospital beds and
      physicians. This situation suggests that an increase in the diagnosis of
      echinococcosis is an unlikely explanation for the epidemic but that there is an
      increase in transmission to the human population.

PMID- 12055798
TI  - A leishmanin skin test survey in the human population of l'Alacanti region
      (Spain): implications for the epidemiology of Leishmania infantum infection in
      southern Europe.
AB  - A study of leishmanin skin test reactors was carried out in 1997 and 1998 in an
      endemic region in southeast Spain, to estimate the magnitude of and the factors
      related to subclinical Leishmania infantum infection. In the main focus of
      leishmaniasis in the region, 11.5% of the children and 52.8% of the adults
      reacted to the skin test. Among the adults, the response was significantly
      greater for males and for those who had resided in the area for > or = 15 years.
      In the whole region, 3.7% 14-year-old students reacted to the skin test, with no
      gender differences. The main factors related to a positive skin test result were
      having a parent or sibling recovered from leishmaniasis (relative risk = 14) and
      living in the rural periphery of the region as opposed to the metropolitan area
      (relative risk = 4). These results indicate a high frequency of subclinical
      leishmaniasis in the region. We postulate that the decline in childhood visceral
      leishmaniasis in southern Europe in the second half of the 20th century is
      related to social changes, which gave rise to a less frequent exposure at a young
      age as well as a lowered susceptibility to disease through nutritional and immune
      improvements.

PMID- 12055799
TI  - Lymphatic filariasis in Lower Shire, southern Malawi.
AB  - Surveys for lymphatic filariasis were carried out for the first time in Lower
      Shire (Nsanje and Chikawawa Districts) of southern Malawi, in April-June 2000.
      There were 3 phases. In phase I, questionnaire surveys in 48 randomly selected
      villages indicated that chronic manifestations of lymphatic filariasis ('swollen
      scrotum' and 'swollen legs') were common and widespread in the area. In phase II,
      volunteers from 10 of the villages reporting frequent manifestations of
      filariasis in phase I were examined with the ICT whole-blood test for Wuchereria
      bancrofti-specific circulating filarial antigen (CFA). The observed prevalence of
      CFA positivity was very high (range, 38.8-79.1% for the villages). In phase III,
      a more detailed parasitological, CFA and clinical investigation was carried out
      in 2 of the high CFA prevalence villages identified in phase II (1 in each
      district). Overall, 18.1% and 22.2% were positive for microfilariae, and 62.3%
      and 64.6% were positive for CFA in the 2 villages. Among those aged > or = 15
      years, 3.7% and 1.3% had leg elephantiasis, and 17.9% and 13.0% (of males only)
      had hydrocoele. In both phase II and III, CFA prevalences were unexpectedly high,
      especially in children. This was probably related to a recent increase in
      transmission of filariasis as a result of extensive flooding in the area prior to
      the study. The study indicated that lymphatic filariasis is highly endemic in the
      Lower Shire area of Malawi, and calls for action towards its control.

PMID- 12055800
TI  - Seroprevalence of toxocariasis in schoolchildren in Trinidad.
AB  - The seroprevalence of toxocariasis was investigated in 1997/98 in 1009
      schoolchildren (aged 5-12 years) throughout Trinidad. Infection, as measured by
      titre, was found to be high compared to values obtained from children in other
      countries. Using an excretory-secretory antigen and performing an ELISA test, it
      was found that 62.3% of children had an IgG antibody titre of > or = 1:100,
      indicating exposure to the parasite, while 27.2% had a titre of > or = 1:800,
      indicating a current or recent infection. Relationships were explored between
      seroprevalence and host factors including age, sex, school location, and other
      risk factors including geophagia, thumb-sucking, presence of other
      gastrointestinal-tract parasitism and pet ownership. There was no significant
      relationship between age and the presence of current or recent infection (P =
      0.746). Boys were significantly more commonly infected than girls as were the
      attendees of rural schools versus urban schools (P < 0.001). The percentage of
      seropositivity among children varied widely from school to school. Pet ownership
      and the absence of pipe-borne water in the household were found to be
      significantly associated with positive serology (P < 0.05). Clinical symptoms
      mostly associated with positive serology were eczema, seizures and chronic cough.
      Recommendations derived from this study include health education in order to
      increase the public awareness on the transmission of the disease, de-worming all
      dogs and cats periodically and the curbing of stray dogs and cats. Environmental
      sanitation measures should include keeping children away from contaminated areas
      and practising proper hygiene after play.

PMID- 12055802
TI  - Plasmodium falciparum: PCR detection and genotyping of isolates from peripheral,
      placental, and cord blood of pregnant Malawian women and their infants.
AB  - Polymerase chain reaction (PCR) is both a sensitive means of detecting malaria
      parasitaemia, and a simple tool for identifying genetic differences in parasites
      infecting human subjects. We compared PCR to microscopy in detection of
      Plasmodium falciparum infection in peripheral, placental and cord blood samples
      collected from 131 pregnant Malawian women and their infants in 1997-99.
      Infections detected by species-specific PCR were genotyped at the merozoite
      surface protein 1 and 2 loci, and minimum numbers of infecting genotypes
      determined. PCR was of similar sensitivity to microscopy in detecting peripheral
      and placental infection, and placental blood PCR was 100% specific compared to
      placental histology. Cord blood parasitaemia was more frequently detected by PCR
      than microscopy, 20% versus 6%. Genotype numbers in peripheral blood (mean 2.36;
      range 1-5), placental blood (mean 2.41; range 1-6) and cord (mean 2.14; range 1
      4) were similar. The frequency of detection of each allelic family did not differ
      between sites. Genotypes from different sites in each patient were compared. In
      69% of women, genotypes were detected in peripheral blood and not placenta, or
      vice versa, suggesting possible differential sequestration of different parasite
      populations. Cord blood genotypes were usually a subset of those in peripheral
      and placental blood, but, in some cases, genotypes were found in cord blood that
      were absent from the mother. Transplacental infection before term, and clearance
      of maternal infection, is postulated.

PMID- 12055801
TI  - South-East Asian ovalocytosis among the population of the Highlands of
      Madagascar: a vestige of the island's settlement.
AB  - In the Madagascar Highlands, 0.76% of children from 168 random primary schools,
      and 19 of 150 families from 3 villages, had oval-shaped erythrocytes. Most
      harboured the deletion in the band 3 gene characteristic of South-East Asian
      ovalocytosis. This genetic trait supports the Indonesian origin of the Madagascar
      settlement.

PMID- 12055803
TI  - Successful conservative management of splenic rupture in vivax malaria.

PMID- 12055804
TI  - Serum ferritin, alpha-tocopherol, beta-carotene and retinol levels in lymphatic
      filariasis.
AB  - Based on a cross-sectional study conducted among 100 adults in 1993 in Tanga,
      Tanzania, the relationship between Wuchereria bancrofti infection and markers of
      iron, vitamin A and vitamin E status was assessed. Potential predictors assessed
      were elephantiasis, hydrocoele, W. bancrofti microfilaria intensity and antigen
      concentration, and intensity of Schistosoma haematobium, hookworm, Trichuris
      trichiura and Ascaris lumbricoides infection, while controlling for age, sex and
      elevated serum alpha-1 antichymotrypsin. Of the 100 adults, 62 had W. bancrofti
      antigenaemia and 43 microfilaraemia, and 21 had elephantiasis. Of the 64 males,
      31 had hydrocoele. W. bancrofti microfilaria intensity was a positive predictor
      of serum ferritin and a negative predictor of serum alpha-tocopherol. In
      contrast, negative relationships observed between W. bancrofti microfilaria
      intensity and serum beta-carotene and retinol were not significant. Neither
      antigen concentration nor clinical manifestations were predictors of
      micronutrient status. Intensity of hookworm infection was associated with lower
      serum ferritin. S. haematobium egg output was not a significant predictor of
      serum ferritin, but was a positive predictor of serum beta-carotene. In
      conclusion, W. bancrofti microfilaria intensity was associated with higher serum
      ferritin, but lower serum alpha-tocopherol. The associations probably reflect
      increased oxidative stress due to microfilariaehost interactions, which could
      play a role in the pathogenesis.

PMID- 12055805
TI  - Progression of lymphatic vessel dilatation in the presence of living adult
      Wuchereria bancrofti.
AB  - Bancroftian filariasis, a mosquito-transmitted disease commonly known as
      elephantiasis, is caused by infection with the parasite Wuchereria bancrofti.
      Infection with this parasite can induce a broad array of chronic debilitating and
      socially stigmatizing conditions, but the pathogenesis of this morbidity remains
      obscure. Recent evidence indicates that in filariasis-endemic areas the primary
      lesion is not lymphatic vessel obstruction but, rather, dilatation. To determine
      the extent to which lymphatic dilatation occurs in the presence of living adult
      W. bancrofti, we performed longitudinal ultrasonographic measurements in 80 men
      (mean age 24 years) in Brazil who had a total of 107 W. bancrofti nests
      detectable by ultrasound. Initial mean lymphatic vessel diameter at the site of
      the worms was 3.4 mm (range, 0.7-11.3), and was greater in men with 2 or more
      nests (3.9 mm) than in those with only one nest (3.0 mm, P = 0.003). During the
      study period (2-35 months, mean, 13.7), lymphatic vessel diameter increased at
      the site of 92 (86.0%) adult worm nests. Mean rate of increase of lymphatic
      vessel diameter was 1.2 mm per person-year (range, 0-0.93 mm per month). In a
      general linear model, no factors, including treatment with antifilarial drugs,
      were significantly associated with rate of vessel diameter increase. Thus,
      lymphatic vessel dilatation progress in the presence of living adult W.
      bancrofti; the rate of this progression is heterogeneous. These data suggest that
      lymphatic dilatation will continue to progress in most infected persons even
      after mass treatment with currently recommended antifilarial drugs. In addition
      to interrupting transmission, the global programme for elimination of lymphatic
      filariasis should address the potential for disease progression in persons who
      remain infected with adult W. bancrofti.

PMID- 12055806
TI  - Inter-observer variation in the assessment of clinical signs in sick Tanzanian
      children.
AB  - We assessed the inter-observer agreement in identification of a range of 24
      clinical signs associated with disease presentation in 327 children aged < 5
      years admitted to hospital in January-June 1999 in Ifakara, southern Tanzania.
      Children with diagnoses of malaria, pneumonia, diarrhoea, anaemia and
      malnutrition were examined independently by 2 clinical officers. Findings were
      recorded on a standard proforma. The Kappa-statistic was used to assess inter
      observer agreement for each sign. Physical signs were more likely to be agreed
      upon by clinicians if they involved inspection than if they involved
      auscultation. The signs included in the Integrated Management of Childhood
      Illness (IMCI) algorithm were found to be largely appropriate (Kappa-scores >
      0.41) although there was only fair agreement (Kappa-score 0.21-0.40) in the
      detection of neck stiffness and chest indrawing and slight agreement in the
      detection of dehydration (Kappa-score 0.199). All objective neurological signs
      were less reliably assessed in infants than in older children. The difficulties
      surrounding the diagnosis of impaired consciousness in young children should
      increase vigilance in the diagnosis and management of neurological complications
      of illnesses in infancy.

PMID- 12055807
TI  - A simple clinical and paraclinical score predictive of CD4 cells counts below
      400/mm3 in HIV-infected adults in Dakar University Hospital, Senegal.
AB  - In industrialized countries the decision to start co-trimoxazole (CMX)
      prophylaxis of HIV-related opportunistic infections is based on the CD4+ cell
      count. The value of CMX prophylaxis has also been demonstrated in Africa, where
      CD4+ cell counts are rarely available. We therefore developed a simple score
      predictive of a threshold CD4+ cell count (400/mm3) below which CMX prophylaxis
      is indicated. In a retrospective cross-sectional study, we collected clinical and
      biological data on 211 HIV-infected patients recruited from January 1996 through
      January 1998 at Fann University Hospital in Dakar, Senegal. Several variables
      were identified as being predictive of a CD4+ cell count below 400/mm3 by
      stepwise logistic regression. Each variable was weighted according to its
      regression coefficient, as follows: male sex (+1), weight loss (+2), body mass
      index < 22 (+2), herpes zoster (+4), tuberculin induration < 5 mm (+3) and
      haemoglobin < or = 10 g/dL (+1). A score of > or = 4 (sum of weights) selected
      patients with CD4+ cell counts below 400/mm3 with a sensitivity of 98% and a
      negative predictive value of 83%. Such a score should be applicable in the
      African context and should facilitate the management of HIV-infected patients,
      especially the prescription of CMX prophylaxis.

PMID- 12055808
TI  - Clinical and immunological risk factors for severe disease in Japanese
      encephalitis.
AB  - Eighty-five paediatric patients in Thailand with acute Japanese encephalitis (JE)
      were studied in 1987-99 to determine risk factors present at hospital admission
      which were associated with severe disease. On univariate analysis, the following
      factors on admission were significantly associated with the combined end-point of
      death or a severe neurological deficit: depressed level of consciousness,
      elevated concentration of cerebrospinal fluid (CSF) protein, low levels of serum
      and CSF IgG antibody against Japanese encephalitis virus (JEV), low level of
      serum IgM antibody against JEV, and a serological response consistent with
      primary flavivirus infection. On multivariate analysis, an initial serum anti-JEV
      IgM < 150 U and the absence of a prior flavivirus infection, presumably dengue,
      remained independent risk factors for death or a severe neurological deficit. The
      ability to mount an early and vigorous JEV-reactive antibody response is
      associated with a better outcome from acute JE. An anamnestic, anti-flavivirus,
      immune response induced by a prior dengue virus infection can be an important
      means of providing this protection.

PMID- 12055809
TI  - Tanapox: first report in a European traveller and identification by PCR.
AB  - Tanapox is a rare pox disease endemic in East Africa. We report the first case of
      tanapox in a European traveller who contracted the disease in 1999 during a short
      visit to Tanzania. The diagnosis was made on clinical grounds and confirmed by
      electron microscopy and a tanapox virus-specific PCR assay.

PMID- 12055810
TI  - The effects of quinine and chloroquine antimalarial treatments in the first
      trimester of pregnancy.
AB  - Quinine (n = 246) was used to treat uncomplicated Plasmodium falciparum and
      chloroquine (n = 130) was used to treat P. vivax, in a total of 376 episodes of
      malaria in the first trimester of pregnancy, in 300 Karen women (Thailand, 1995
      2000). Parasites were still present on day 6 or 7 in 4.7% (11/234) of episodes
      treated with quinine. The overall 28 day parasite reappearance rate following
      quinine was 28.7% (60/209) for primary treatments and 44% (11/25) for re
      treatments. Quinine treatment resulted in a high rate of gametocyte carriage:
      person-gametocyte-weeks = 42.5 (95% CI 27.8-62.1) per 1000 woman-weeks. For P.
      vivax, the reappearance rate for all episodes by day 28 was 4.5% (5/111).
      Significantly more women complained of tinnitus following quinine treatment
      compared to on admission: 64.5% (78/121) vs 31.6% (59/187), P < 0.001. Using
      survival analysis, the community rate of spontaneous abortion in women who never
      had malaria in pregnancy, 17.8% (16.5-19.0), did not differ significantly from
      rates in women treated with quinine: 22.9% (95% CI 15.5-30.3), or chloroquine:
      18.3% (95% CI 9.3-27.3), P = 0.42. Pregnancies exposed to quinine or chloroquine
      and carried to term did not have increased rates of congenital abnormality,
      stillbirth or low birthweight. These results suggest that therapeutic doses of
      quinine and chloroquine are safe to use in the first trimester of pregnancy.

PMID- 12055811
TI  - Treatment of Plasmodium falciparum malaria with quinine in children in Guinea
      Bissau: one daily dose is sufficient.
AB  - We have earlier obtained good results in falciparum malaria by treating children
      with low doses of quinine for 7 days in Guinea-Bissau. In order to further
      simplify treatment, we compared outcome in 100 children with falciparum malaria
      treated in 1999/2000 for 7 days with 15 mg quinine salt/kg/dose twice daily
      (group I), 100 children treated with 7.5 mg quinine salt/kg/dose twice daily
      (group II), and 100 children treated with one single daily dose of 15 mg/kg. One
      day 28, parasites had reappeared in 12%, 15%, and 9%, respectively. These results
      are similar to what has been found after previous successful treatment regimens.
      Apart from a higher incidence of vomiting during the first 24 h of treatment in
      the groups treated with 15 mg/kg/dose no significant differences in symptoms or
      side-effects were found between the groups. In patients suffering from
      uncomplicated malaria, treatment with quinine can be simplified to one single
      dose of 15 mg/kg bodyweight whenever logistics make 2 daily doses less feasible.

PMID- 12055812
TI  - Ivermectin and albendazole alone and in combination for the treatment of
      lymphatic filariasis in Ghana: follow-up after re-treatment with the combination.
AB  - The efficacy of re-treatment with the combination of ivermectin (150-200
      micrograms/kg bodyweight) and albendazole (400 mg) on Wuchereria bancrofti
      microfilaraemia was assessed in 1997-99 in 4 groups of individuals from coastal
      Ghana, which 1 year previously had received a primary treatment with placebo (n =
      38), albendazole (n = 39), ivermectin (n = 34) or combination of albendazole and
      ivermectin (n = 42), respectively. One year after the re-treatment, an overall
      mean reduction in microfilarial intensity of 76.2% in relation to the intensity
      before re-treatment was observed, with no statistical significant difference
      between the 4 groups. The groups given primary treatment with placebo or the drug
      combination showed re-treatment reductions which were lower (72.5% and 69.8%,
      respectively) but not statistically significantly different from the reduction
      observed 1 year after the primary treatment with the combination (86.7%). The
      efficacy of the combination treatment thus appeared to be largely independent of
      the type of primary treatment given and multiplicative when used repeatedly.

PMID- 12055813
TI  - Comparative clinical studies of nitazoxanide, albendazole and praziquantel in the
      treatment of ascariasis, trichuriasis and hymenolepiasis in children from Peru.
AB  - Three randomized clinical studies were conducted in 2000 to evaluate the efficacy
      of nitazoxanide paediatric suspension compared to albendazole in the treatment of
      ascariasis and trichuriasis and praziquantel in the treatment of hymenolepiasis
      in children from Cajamarca, Peru. Nitazoxanide was administered at a dose of 100
      mg (age 1-3 years) or 200 mg (age 4-11 years) twice daily for 3 days, albendazole
      as a 400-mg single dose and praziquantel as a 25-mg/kg single dose. Post
      treatment parasitological examinations were carried out on 3 faecal samples, each
      collected on a different day between 21 and 30 days following initiation of
      treatment. Nitazoxanide cured 89% (25/28), 89% (16/18) and 82% (32/39) of the
      cases of ascariasis, trichuriasis and hymenolepiasis respectively compared with
      91% (32/35), 58% (11/19) and 96% (47/49) for the comparator drugs. Each of the
      drugs produced egg reduction rates in excess of 98%. There were no significant
      adverse events or abnormalities in haematology or clinical chemistry values or
      urinalysis.

PMID- 12055814
TI  - Is the exclusion of children under 24 months from anthelmintic treatment
      justifiable?
AB  - There are no reports documenting toxicity or adverse effects after treatment of
      children aged < 24 months with benzimidazole derivatives and there is an urgent
      need to clarify this point in light of the potential detrimental effect that soil
      transmitted helminthiasis has on this age-group. A total of 653 treatments (317
      mebendazole 500 mg; 336 placebo) were administered in 1996/97 to 212 children
      aged < 24 months as part of a 1-year anthelmintic drug study conducted among
      preschool-age children in Tanzania. Data on fever, cough, diarrhoea, dysentery
      and acute respiratory illness were collected 1 week following the treatment. No
      differences between the occurrence of adverse effects in the 2 groups were
      observed. In light of the potential nutritional benefit achieved by regular
      deworming in this young age-group, the policy that excludes children aged < 24
      months from treatment should be re-considered.

PMID- 12055815
TI  - Clinical efficacy of chloroquine or sulfadoxine-pyrimethamine in children under
      five from south-western Uganda with uncomplicated falciparum malaria.
AB  - We conducted a 14-day study (during March-May 1998) to assess the efficacy of
      chloroquine and sulfadoxine-pyrimethamine (SP) for treating uncomplicated
      Plasmodium falciparum malaria in Uganda. Overall treatment failure rates were 43
      (81.1%) of 53 chloroquine recipients and 16 (25.0%) of 64 SP patients. Strategies
      to improve the life-span of standard and affordable anti-malarial drugs are
      needed.

PMID- 12055816
TI  - Changes in Escherichia coli resistance to co-trimoxazole in tuberculosis patients
      and in relation to co-trimoxazole prophylaxis in Thyolo, Malawi.
AB  - In Thyolo district, Malawi, an operational research study is being conducted on
      the efficacy and feasibility of co-trimoxazole prophylaxis in preventing deaths
      in HIV-positive patients with tuberculosis (TB). A series of cross-sectional
      studies were carried out in 1999 and 2001 to determine (i) whether faecal
      Escherichia coli resistance to co-trimoxazole in TB patients changed with time,
      and (ii) whether the resistance pattern was different in HIV-positive TB patients
      who were taking co-trimoxazole prophylaxis. Co-trimoxazole resistance among E.
      coli isolates in TB patients at the time of registration was 60% in 1999 and 77%
      in 2001 (P < 0.01). Resistance was 89% among HIV-infected TB patients (receiving
      cotrimoxazole), while in HIV-negative patients (receiving anti-TB therapy alone)
      it was 62% (P < 0.001). The study shows a significant increase of E. coli
      resistance to co-trimoxazole in TB patients which is particularly prominent in
      HIV-infected patients on co-trimoxazole prophylaxis. Since a high degree of
      plasmid-mediated transfer of resistance exists between E. coli and the Salmonella
      species, these findings could herald limitations on the short- and long-term
      benefits to be expected from the use of co-trimoxazole prophylaxis in preventing
      non-typhoid Salmonella bacteraemia and enteritis in HIV-infected TB patients in
      Malawi.

PMID- 12055817
TI  - Malaria therapy reinoculation data suggest individual variation of an innate
      immune response and independent acquisition of antiparasitic and antitoxic
      immunities.
AB  - Malaria therapy reinoculation data were examined for the possible detection of
      effects attributable to stable individual host-specific factors, through
      correlation between descriptive variables of first and second infections. Such an
      effect was demonstrated with respect to the first local maximum of the asexual
      parasite density, i.e., the density at which a host controls parasite growth. The
      effect was seen between an individual host's first and second Plasmodium
      falciparum infection, as well as between an individual host's first malaria
      infection with P. ovale and second malaria infection with P. falciparum. We give
      reasons to believe that the main underlying mechanism is individual variation of
      an innate immune response. The data were also examined for systematic changes
      from first to second P. falciparum infection, as indicators of acquired immunity.
      In addition to the well-known reduction in parasite density, the data show the
      early development of apparent parasite tolerance. We give reasons to interpret
      the latter as antitoxic immunity.

PMID- 12055819
TI  - Prevalence of hepatitis E virus antibodies among different groups in the
      Amazonian basin.

PMID- 12055818
TI  - Antibody isotype responses to Schistosoma japonicum antigens in subjects from a
      schistosomiasis area with repeated praziquantel chemotherapy compared with a new
      endemic zone in Hunan Province, P.R. China.
AB  - To demonstrate the dynamics of specific antibody isotypes against schistosome
      adult worm (AWA) and soluble egg (SEA) antigens, we evaluated (in 1999-2000) 112
      subjects infected with Schistosoma japonicum from 2 regions of Hunan Province,
      China. Fifty-eight subjects were from Area A, a well-known endemic area with
      repeated chemotherapy. Area B (n = 54) is a new endemic focus in another part of
      the same province. Serum samples were collected prior to praziquantel (PZQ)
      chemotherapy, and at 2 and 12 months post-treatment. IgM, IgA, IgG, IgG2, IgG4
      and IgE antibodies to AWA and SEA were measured by quantitative enzyme-linked
      immunosorbent assay (ELISA). Pre-treatment antibody isotype levels from Area A,
      except IgA against AWA and SEA, were significantly higher than those from Area B.
      In response to chemotherapy, most antibody isotype levels fell or remained
      stable. However, in Area A there was a significant increase in the IgA, IgE and
      IgG4 responses to AWA 2 months after PZQ--which fell to approach pre-treatment
      levels by 12 months. A similar response was seen in Area B with IgE and IgG4 to
      AWA. Levels of all AWA-specific IgE and IgG4 were significantly higher in
      subjects from Area A compared with Area B at all time-points. AWA-IgE levels
      demonstrated significant linear correlations with age and number of previous PZQ
      treatments in Area A only. All SEA-specific isotypes in both areas fell
      significantly in response to treatment--except IgE, which remained stable in both
      area. All SEA-specific isotype levels (except IgA) were significantly higher from
      Area A at baseline. This significant difference was maintained through 12-months
      follow-up for IgE, IgG2 and IgG4 only. This study suggests that multiple episodes
      of schistosome infection may be required to generate antibody isotype levels that
      have been associated with resistance to re-infection in other studies. Further, a
      surrogate marker of successful chemotherapy (AWA-IgG4) performed less effectively
      in patients with previous treatment courses.

PMID- 12055820
TI  - Lack of influence of red palm oil on severity of malaria infection in pre-school
      Nigerian children.
AB  - Vitamin A supplements are reported to reduce febrile episodes of malaria and
      parasite counts, especially in children aged 12-36 months. Red palm oil (RPO) is
      a good source of vitamin A, is rich in alpha- and beta-carotene and is as
      effective as high-dose retinyl palmitate supplements in improving vitamin A
      status. In western Nigeria, where malaria is endemic, RPO is widely used and
      consumption can be measured using plasma alpha-carotene as a proxy biomarker
      since there are few other prominent sources of this carotene in the diet. The
      influence of RPO consumption on malaria was investigated in 207 children (aged 0
      60 months) who presented with fever in August-October 1999 at several hospital
      clinics around Ile-Ife. Medical and anthropometric data, body temperature,
      parasitaemia and plasma C-reactive protein (CRP), retinol, carotenoids and
      tocopherols were measured in the children. Mothers were interviewed on usage of
      cooking oil and mosquito nets in the home, education and occupation. Most
      families used RPO and median plasma concentrations of both alpha-carotene (0.518
      mumol/L) and beta-carotene (0.698 mumol/L) in the children were high. Using body
      temperature, parasite density and plasma CRP as markers of disease severity,
      multiple linear regression analysis was carried out on those for whom complete
      data were available (n = 138), separated into 3 age-groups of < 12 months (n =
      37), 12-36 months (n = 68) and > 36 months (n = 33). In the absence of plasma
      retinol, plasma alpha-carotene explained 13.9% of the variance in parasite
      density (P = 0.013) but only in children aged > 36 months. The relationship with
      disease severity was negative, i.e., there was some evidence that RPO usage
      protected against malaria, and other dietary indices generally indicated that
      better nutritional status was associated with a lower severity of malaria.

PMID- 12055821
TI  - Molecular probes and the polymerase chain reaction for detection and typing of
      Leishmania species in Mexico.
AB  - Leishmaniasis in Mexico is a public health problem because all the clinical forms
      have been recorded in most Mexican states. We studied patients showing clinical
      symptoms of any form of leishmaniasis, from several endemic areas. Bone marrow
      samples, aspirates or skin biopsies were taken and deoxyribonucleic acid (DNA)
      was extracted and amplified by the polymerase chain reaction (PCR) with universal
      primers AJS1 and DeB8, specific for the Leishmania subgenus Leishmania. The PCR
      products were then hybridized by dot- or Southern blotting and probed with probe
      9.2, specific for the L. mexicana complex. If hybridization did not occur, the
      DNA was amplified with primers D1 and D2, specific for members of the L. donovani
      complex, and PCR products were hybridized with probe B4Rsa, also specific for the
      L. donovani complex. DNA was also amplified with primers B1 and B2, specific for
      the subgenus Viannia, and the PCR products were hybridized with probe B18,
      specific for the L. braziliensis complex. It was found that in Tabasco and
      Veracruz, Mexico, localized cutaneous leishmaniasis (LCL) is caused by infection
      with members of the L. mexicana complex, whereas in the states of Nayarit and
      Campeche it was due to infection with the L. mexicana and/or L. braziliensis
      complexes. Visceral leishmaniasis was caused by L. (L.) chagasi, mainly in the
      states of Chiapas and Guerrero, and by L. (L.) mexicana in one immunocompromised
      patient from Tabasco.

PMID- 12055822
TI  - Molecular epidemiology of cutaneous leishmaniasis in Venezuela.
AB  - This paper discusses the utility of a set of primers (3J1, 3J2) designed from a
      repetitive nuclear deoxyribonucleic acid sequence for the diagnosis of Leishmania
      braziliensis infection in samples obtained from humans, insect vectors and
      mammalian reservoir hosts from different endemic areas in Venezuela. A high
      incidence of Leishmania (Viannia) braziliensis infection was found in the endemic
      areas studied. The sensitivity and specificity of the primers used were adequate
      for the identification of the natural vectors and reservoir hosts of L. (V.)
      braziliensis. The polymerase chain reaction was more sensitive than culture and
      stained smear examination in the diagnosis of cutaneous leishmaniasis, detecting
      80% of cases compared to 42% and 72%, respectively.

PMID- 12055823
TI  - Genetic variation in populations of Leishmania species in Brazil.
AB  - The population structure of strains of Leishmania (Viannia) braziliensis sensu
      lato from Para State and Parana State in Brazil, of L. (V.) shawi and L.
      (Leishmania) amazonensis from Para State, and the relationships of type strains
      of the subgenera L. (Viannia) and L. (Leishmania) were examined by the random
      amplified polymorphic deoxyribonucleic acid (RAPD) technique. Four different
      primers (M13-40, QG1, L15996 and delta gt11R) were used. The bands were analysed
      using the neighbor-joining (NJ) and unweighted pair-group method with arithmetic
      averages (UPGMA) algorithms of the MEGA package. The topology of the NJ and UPGMA
      trees was very similar but they were not always identical. Both trees
      differentiated the standard strains of the different species. Strains from the
      same location were grouped together only in the UPGMA phenogram of the M13-40
      primer. L. (V.) braziliensis isolates from Parana State were genetically closer
      to those from Paragominas, Para State than to those from the Amazonian regions of
      Carajas in Para State and Peru. The relationship was not dependent on
      geographical distance. It is postulated that the groups arose from different
      origins, in which the Amazonian stocks were related to Psychodopygus sand flies
      while the Parana strains originated from a gene pool transmitted by Lutzomyia
      sand flies such as Lutzomyia (Nyssomyia) whitmani. Transmission by Ps. complexus
      in Paragominas is considered to be a secondary adaptation from the Lutzomyia
      leishmanial gene pool. Although the vectors of L. (V.) braziliensis are poorly
      known in the Amazon region, there is strong evidence that the major vectors are
      all Psychodopygus spp. There was a high degree of genetic variability amongst the
      L. (V.) shawi strains and there was no clear grouping according to the strains'
      origins. The genetic variability amongst L. (L.) amazonensis strains from the
      same locations was much lower but they formed 2 groups which coincided with their
      origin. Our results support the clonal population structure of Leishmania
      isolates and suggest that their distribution is related to the origin of the gene
      pool as well as to present vector and reservoir movements.

PMID- 12055824
TI  - American cutaneous leishmaniasis in domestic dogs: an example of the use of the
      polymerase chain reaction for mass screening in epidemiological studies.
AB  - Domestic dogs (Canis familiaris) are firmly incriminated as reservoir hosts of
      zoonotic visceral leishmaniasis. As an increasing number of studies have reported
      high infection rates with American cutaneous leishmaniasis (ACL) in dogs, it is
      suggested that they should also be incriminated as reservoir hosts of ACL. The
      evidence to incriminate dogs as ACL reservoir hosts is reviewed, and we conclude
      that there is, as yet, only circumstantial evidence to support that claim, one of
      the reasons being that diagnostic tests (mainly serology) used in the studies
      underestimate the true rate of infection. We report results from the first large
      scale study to measure ACL infection rates using the polymerase chain reaction
      (PCR). A high prevalence of ACL was detected in blood and bone marrow of dogs
      surveyed in an area of Peru endemic for Leishmania braziliensis and L. peruviana,
      providing further evidence for their suspected role as ACL reservoir hosts.
      However, the relatively low ACL prevalence detected in symptomatic dogs (i.e.,
      dogs with ACL lesions or scars) demonstrated that PCR alone cannot be the
      diagnostic 'gold standard' for mass screening of samples in epidemiological
      studies.

PMID- 12055825
TI  - Drug sensitivity of Leishmania species: some unresolved problems.
AB  - Leishmania species show a significant variation in their sensitivity to
      established and experimental drugs. Molecular techniques to identify species in
      clinical infections rapidly could be used to guide treatment. Molecular markers
      are required to detect and monitor acquired resistance to antimonial drugs.
      Reporter genes and the polymerase chain reaction will improve assays both in
      vitro and in vivo for the identification and evaluation of new drugs.

PMID- 12055826
TI  - The influence of the genetic complexity of Plasmodium falciparum infections on
      the epidemiology of malaria.
AB  - Genetic characterization of malaria parasites in human blood stage infections has
      provided important insights into the genetics of Plasmodium falciparum
      populations and given rise to a field frequently referred to as 'molecular
      epidemiology'. This might be defined as the combination of parasite population
      genetic analysis with clinical and epidemiological analysis of a study population
      in order to achieve a better understanding of infection and immunity and long
      term patterns of disease incidence and severity. Longitudinal studies on
      infection and clinical disease incidence, combined with improvements in the
      sensitivity of detection of low level, normally asymptomatic, parasite infections
      have formed an important part of this effort. Two molecular epidemiological
      studies of malaria under low and moderate intensity transmission, in Sudan and
      Ghana respectively, are reviewed here to illustrate how the parasite genotyping
      approaches based on deoxyribonucleic acid which Douglas Barker pioneered in the
      study of Leishmania have developed after their application to malaria research.

PMID- 12055827
TI  - Genetic polymorphism of Plasmodium falciparum isolates from Loreto, Peru.
AB  - Eight genotypes of Plasmodium falciparum were detected after analysing blood
      samples obtained from 30 Peruvian jungle-dwelling patients in Loreto, a high
      transmission area for P. falciparum, using amplification of the polymorphic
      marker gene GLURP (glutamate-rich protein). Genotypes I (GLURP450) and VIII
      (GLURP800) were the most common (15/30 and 13/30, respectively). This single copy
      gene showed 15 patients to be infected with a single genotype of P. falciparum;
      the other 15 were infected with mixed genotypes, one of them with 4 genotypes.
      These findings are compatible with a high genetic complexity of P. falciparum.
      Further investigations are needed, using this and other markers, in order to
      design malaria control measures in Peru.

PMID- 12055828
TI  - Epidemiology and diagnosis of African trypanosomiasis using DNA probes.
AB  - The accurate identification of trypanosome species has been a challenging problem
      in the epidemiology of African trypanosomiasis, both human and animal. The last
      10 years have seen great progress through the application of deoxyribonucleic
      acid (DNA) probe technology, although this has also revealed greater complexity
      than supposed. While a single repetitive DNA probe can identify all members of
      the subgenus Trypanosoma (Trypanozoon), including the human pathogens T. brucei
      gambiense and T. b. rhodesiense as well as the non-tsetse-transmitted
      trypanosomes T. evansi and T. equiperdum, at least 6 probes are needed to
      distinguish members of the subgenus Nannomonas, in which only 2 species, T.
      congolense and T. simiae, were previously recognized. Similarly, the subgenus
      Duttonella appears to consist of more than one species. Use of this battery of
      DNA probes to identify the trypanosomes carried by tsetse flies in the field has
      yielded some surprises about the accuracy (or inaccuracy) of previous
      identification methods. An unexpectedly high prevalence of mixed infections has
      been found in all the field studies carried out so far. The large number of
      infections that remain unidentified by the available probes suggests the
      existence of other, as yet unknown, trypanosome species. Limited use of the
      polymerase chain reaction has been made for diagnosis of human and animal
      trypanosomiasis, due to its high cost.

PMID- 12055829
TI  - Natural immunity to human African trypanosomiasis: trypanosome lytic factors and
      the blood incubation infectivity test.
AB  - This review focuses on the epidemiology of human African trypanosomiasis: why it
      occurs in humans, the current methods of surveillance, and the drugs available to
      treat it. Emphasis is placed on the identification of human-infective
      trypanosomes by the blood incubation infectivity test. This test distinguishes
      between trypanosomes that are non-infective for humans and those that are
      potentially infective. Currently the test requires incubation of parasites with
      human serum before injection into mice; any surviving parasites are considered
      human-infective. The factors in serum that kill all non-human-infective parasites
      are known as trypanosome lytic factors. The paper details the biochemistry of
      these factors and recommends standardization of the test based on current
      knowledge. This test can be used to screen animals with trypanosomiasis, in order
      to evaluate their role during endemic and epidemic human African trypanosomiasis.

PMID- 12055830
TI  - DNA thermodynamic pressure: a potential contributor to genome evolution.
AB  - Codon usage bias is a feature of living organisms. The origin of this bias might
      be explained not only by external factors but also by the nature of the structure
      of deoxyribonucleic acid (DNA) itself. We have developed a point mutation
      simulation program of coding sequences, in which nucleotide replacement follows
      thermodynamic criteria. For this purpose we calculated the hydrogen bond-like and
      electrostatic energies of non-canonical base pairs in a 5 bp neighbourhood.
      Although the rate of non-canonical base pair formation is extremely low, such
      pairs occur with a preference towards a guanine (G) or cytosine (C) rather than
      an adenine (A) or thymine (T) replacement due to thermodynamic considerations.
      This feature, according to the simulation program, should result in an increase
      in the GC content of the genome over evolutionary time. In addition, codon bias
      towards a higher GC usage is also predicted. DNA sequence analysis of genes of
      the Trypanosomatidae lineage supported the hypothesis that DNA thermodynamic
      pressure is a driving force that impels increases in GC content and GC codon
      bias.

PMID- 12055831
TI  - Triatomine vectors of Trypanosoma cruzi: a molecular perspective based on nuclear
      ribosomal DNA markers.
AB  - Chagas disease (American trypanosomiasis) is mainly transmitted by blood-sucking
      bugs of the reduviid subfamily Triatominae (Hemiptera: Prosorrhyncha). Control
      strategies are directed mainly against these insect vectors, as no vaccine is
      available and, except in the very early stage of infection, there is no effective
      chemotherapy. Studies of deoxyribonucleic acid (DNA) will lead to major advances
      in our knowledge of Triatominae and their relationships to Chagas disease
      transmission, epidemiology and control. Analyses of complete sequences of nuclear
      genes coding for ribosomal ribonucleic acid (rRNA) (rRNA genes) and spacers
      furnish significant information at the levels of higher taxons, genera, species,
      subspecies, hybrids, varieties and populations of Triatominae. This paper briefly
      reviews the contributions of studies on the slowly-evolving 18S or small subunit
      (SSU) rRNA gene and the quickly-evolving second internal transcribed spacer (ITS
      2). The whole 18S rRNA gene is a useful marker for supraspecific relationships in
      Triatominae. ITS-2 is complementary to it, enabling resolution at specific and
      infraspecific levels. All the evidence suggests that ITS-2 will become the DNA
      marker of excellence for studies of Triatominae at specific and subspecific
      levels, as it is in other groups of organisms. Possible applications of data
      obtained from the study of rRNA and ITS-2 sequences of Triatominae are discussed.

PMID- 12055832
TI  - Validation of the polymerase chain reaction for the diagnosis of human cutaneous
      leishmaniasis in north-west Colombia.
AB  - Leishmania species of the subgenus Viannia account for 88% of all cases of
      leishmaniasis recorded in Colombia. Correct diagnosis is essential as infection
      with members of this subgenus can produce disfiguring destruction of the mucosa.
      Several methods are available to diagnose leishmaniasis in clinical samples. More
      recently, the polymerase chain reaction (PCR) has been used, with varying
      sensitivities and specificities depending on the primers used. In this paper we
      report on the sensitivity and specificity of PCR primers B1/B2 used on clinical
      samples and compare their use to the conventional parasitological methods. PCR
      alone is more sensitive than any single conventional method used, but a
      combination of conventional methods produced comparable sensitivity. PCR is well
      suited for use in selected cases and as a test for mucosal leishmaniasis.

PMID- 12055833
TI  - The method used to sample ulcers influences the diagnosis of cutaneous
      leishmaniasis.
AB  - Before beginning treatment for cutaneous leishmaniasis, parasitological
      confirmation of the disease is required. The most commonly used diagnostic
      procedures are microscopy and culture of samples taken from the active edge of
      the lesion. In this study, we compared the sensitivity of previous diagnostic
      procedures with the polymerase chain reaction (PCR), using smears taken from the
      edge of the lesion and its centre. The sensitivity was greater with smears taken
      from the centre of the lesion, both for microscopical examination (85%) and for
      PCR (81%), compared to those obtained from the edge of the lesion (69% and 58%
      respectively). When PCR was carried out on biopsy material from the edge of the
      lesion the sensitivity was 63%.

PMID- 12055834
TI  - Parasitological and immunological follow-up of American tegumentary leishmaniasis
      patients.
AB  - A long-term evaluation of human American tegumentary leishmaniasis patients was
      conducted to detect immunological and/or parasitological indicators associated
      with cure or protection against leishmaniasis. Cutaneous leishmaniasis (CL) and
      mucosal leishmaniasis (ML) patients from endemic areas of Leishmania braziliensis
      infection in Brazil were studied during the active disease, at the end of
      therapy, and up to 10 years after the end of therapy. For immunological studies,
      lymphocyte proliferative responses, phenotypic characterization of CD4+ and CD8+
      T cells reactive to L. braziliensis and cytokine production in vitro were
      assayed. In CL, with its tendency for healing lesions, at or shortly after the
      completion of therapy the ratio of CD4+ to CD8+ T cells was approximately one and
      production of interferon gamma (IFN gamma) remained roughly constant. In ML,
      these apparently beneficial CD4+/CD8+ ratios and cytokine patterns appeared
      later. The long-term memory T cell responses were associated with preferential
      induction of CD4+ subpopulations and IFN gamma production that probably led to
      protection against relapses or reinfection. Deoxyribonucleic acid (DNA) was
      isolated from peripheral blood and oligonucleotides that amplify the conserved
      region of the minicircle molecules of Leishmania were used in a 'hot-start'
      polymerase chain reaction (PCR). Leishmania DNA was found in about one-quarter of
      the patients with active disease as well as in individuals who had received
      chemotherapy. The PCR was also positive in one-third of the individuals with a
      positive skin test but no past or present history of leishmaniasis. The well
      modulated T cell response leading to long-term protection observed in CL patients
      could result from a favourable host genetic background and/or a particular
      parasite genotype, leading to a beneficial T cell immune response even in the
      presence of parasite antigens. The possibility of parasite persistence after
      clinical cure suggests that the immune response can control, but not fully
      eliminate, the infection. It could prevent the parasite from causing disease,
      maintaining a leishmanial antigen-specific response and hampering reinfection.

PMID- 12055835
TI  - Visceral leishmaniasis in India: promises and pitfalls of a PCR-based blood test.
AB  - Traditional methods of diagnosing visceral leishmaniasis (kala-azar) in India
      suffer from a number of disadvantages. Amplification of multicopy nuclear genes
      and messenger ribonucleic acid of Leishmania by the polymerase chain reaction
      (PCR) was evaluated as an alternative assay under various clinical conditions.
      PCR of peripheral blood has the highest absolute sensitivity among all the
      available procedures, and is particularly useful for detecting parasites in early
      infections, post kala-azar dermal leishmaniasis, concurrent infections and
      immunocompromised cases, but is not so reliable for late infections. PCR of
      immunopurified blood mononuclear cells indicated the association of parasites
      with monocytes as well as non-monocyte cell types.

PMID- 12055836
TI  - A nested polymerase chain reaction (Ln-PCR) for diagnosing and monitoring
      Leishmania infantum infection in patients co-infected with human immunodeficiency
      virus.
AB  - We investigated a Leishmania-specific nested polymerase chain reaction (Ln-PCR)
      for the diagnosis and treatment monitoring of L. infantum infections in patients
      co-infected with human immunodeficiency virus (HIV). Peripheral blood and bone
      marrow samples from 89 HIV patients in Spain suspected of having leishmaniasis
      were examined by different diagnostic techniques (Ln-PCR, microscopy, NNN culture
      and indirect fluorescent antibody test). The sensitivity of Ln-PCR compared with
      microscopy and culture of bone marrow was 95.45% using blood and 100% when using
      bone marrow. 38 of these patients with confirmed leishmaniasis were entered in a
      chemotherapy trial (reported elsewhere), and samples from them were collected
      before treatment, one month after treatment ended and during follow-up (1-20
      months), and examined similarly. Ln-PCR was shown to be a good method for testing
      efficacy of treatment and for predicting relapses after treatment (relapses were
      predicted on average 5 months earlier than when using classical diagnostic
      techniques). We suggest that Ln-PCR (especially using peripheral blood) should be
      the technique of choice for diagnosis, monitoring the success of treatment, and
      predicting relapses in patients with HIV and suspected or confirmed L. infantum
      infection.

PMID- 12055837
TI  - A nested polymerase chain reaction for diagnosis and follow-up of human visceral
      leishmaniasis patients using blood samples.
AB  - A nested polymerase chain reaction (PCR) assay for the diagnosis of human
      visceral leishmaniasis (VL) due to Leishmania infantum infection was developed
      using primers selected from the parasite's genomic deoxyribonucleic acid (DNA).
      The assay, which is based on the use of leucocytes separated from blood samples
      by Ficoll-Paque centrifugation, was compared with culture in vitro. Blood samples
      were collected from 17 patients in Spain with a history of clinical VL, 15 of
      whom were also infected with human immunodeficiency virus (HIV) (13 samples
      during the VL episode and 31 samples during post-treatment monitoring) and one
      sample was collected from each of 28 patients with HIV infection and fever but no
      history of VL. The nested PCR using blood detected all the cases of
      parasitologically confirmed, clinically active VL, while culture detected 92%.
      The nested PCR detected Leishmania DNA in 18% of the HIV-infected patients with
      fever and no history of VL, none of whom gave a positive culture. Follow-up
      examination of the VL patients by nested PCR and culture demonstrated the
      persistence of L. infantum in blood for a long time after treatment.

PMID- 12055838
TI  - Diagnosis of leishmaniasis in Maltese dogs with the aid of the polymerase chain
      reaction.
AB  - Visceral leishmaniasis due to infection with Leishmania infantum (a member of the
      L. donovani complex) has been known in Malta since the beginning of the century.
      In 1946, when human diseases became compulsorily notifiable on the islands, the
      leishmaniasis figures were 1264 visceral cases, 36 cutaneous cases and 5
      unspecified. Five cases of cutaneous infection were reported in 1997 and 23 cases
      of cutaneous and 3 of visceral infection in January-October 1998. There may be
      considerable under-reporting of the disease. Figures of between 18% and 47% have
      been reported for canine leishmaniasis. This large discrepancy between reservoir
      and human hosts suggests that the canine reservoir could be a serious threat and
      is worthy of careful examination. This pilot study was carried out to determine
      the proportion of dogs serologically positive for leishmaniasis in order to
      assess the necessity for a possible control programme in Malta. Using 60 canine
      blood samples from the Maltese islands, we tested for deoxyribonucleic acid (DNA)
      of the L. donovani complex using the polymerase chain reaction (PCR). The samples
      had all been subjected to the indirect immunofluorescent antibody test (IFAT) and
      a direct comparison was made. DNA was extracted using the phenol/chloroform
      method and amplified with primers specific for kinetoplast mini-circle DNA of the
      L. donovani complex and L. major, Southern blotted and hybridized with a radio
      labelled probe specific for the L. donovani complex. Twelve of the samples gave
      positive results in the IFAT, whilst 37 (62%) were positive by PCR and
      hybridization. All samples from 36 dogs from a non-endemic area in the UK were
      negative by PCR. Five of the 12 samples positive by IFAT gave negative PCR
      results.

PMID- 12055840
TI  - Molecular diagnosis of toxoplasmosis.
AB  - Toxoplasmosis is an anthropozoonotic disease endemic world-wide, caused by the
      apicomplexan Toxoplasma gondii. Although the course of infection is generally
      benign, it can cause significant morbidity and mortality in the developing fetus
      and in immunocompromised individuals. Biological diagnosis classically relies
      upon serology and direct detection of the parasite by inoculation to laboratory
      animals. In the past decade, the use of the polymerase chain reaction (PCR) has
      made a significant improvement in both the prenatal diagnosis of congenital
      toxoplasmosis and the detection of acute disease in the immunocompromised
      patient. Nevertheless, like many 'in-house' PCR assays, the PCR-Toxoplasma
      suffers from lack of standardization and variable performance according to the
      laboratory. A wide variety of primers has been used in different assays, but few
      comparative tests have been performed. Moreover, in contrast to other parasitic
      diseases, PCR-Toxoplasma has not yet attained a sufficient level of sensitivity,
      regardless of the clinical condition considered. These drawbacks are discussed,
      together with the undoubted gain that PCR has brought to this difficult
      diagnosis.

PMID- 12055839
TI  - Alternative polymerase chain reaction method to identify Plasmodium species in
      human blood samples: the semi-nested multiplex malaria PCR (SnM-PCR).
AB  - A simplified protocol for the identification of Plasmodium species by semi-nested
      multiplex polymerase chain reaction (SnM-PCR) in human blood samples is compared
      with microscopical examination of thin and thick blood films in 2 field trials in
      Cote d'Ivoire and Cameroon. Also, dried blood spots or liquid blood collected
      from Dutch soldiers returning from Goma, Zaire (n = 141), Angola (n = 40), and
      from Marechaussee (Dutch border police) returning from various parts of the world
      (n = 161) were examined, together with miscellaneous other material obtained from
      laboratories and hospitals. The method is based on features of the small subunit
      nuclear ribosomal ribonucleic acid (RNA) gene (ssrDNA), a multicopy gene which
      possesses both highly conserved domains and domains characteristic for each of
      the 4 human malaria parasites. The first reaction of the SnM-PCR includes a
      universal reverse primer with 2 forward primers specific for Plasmodium and
      mammals, respectively. The mammalian-specific primer was included as a positive
      control to distinguish uninfected cases from simple PCR failures. The second PCR
      reaction includes a Plasmodium-specific forward primer plus species-specific
      reverse primers for P. vivax, P. ovale, P. falciparum and P. malariae. The
      technique worked better with samples collected in the field as dried blood spots
      on filter paper and heparinized blood rather than with frozen pelleted blood; it
      was more sensitive and more specific than the standard microscopical examination.

PMID- 12055841
TI  - Microsatellite DNA: a tool for population genetic analysis.
AB  - Microsatellite deoxyribonucleic acid repeats provide a source of high variability
      that makes them ideal for use in studies requiring such molecular markers,
      including large population studies and genetic typing of individuals for kinship
      investigations. This paper provides reviews of the use of such markers in
      parasitology. Most studies to date have been carried out using protozoan and
      vector species. Recent investigations have, however, demonstrated their
      usefulness in the study of helminths, illustrating their ability to distinguish
      between individuals within hosts as well as from different hosts. The detection
      of microsatellites within parasites has provided a tool that will prove
      invaluable in parasitology and should lead to significant advances in our
      understanding of the processes that affect the organisms' population genetic
      structure.

PMID- 12055842
TI  - Molecular diagnosis of theileriosis and heartwater in bovines in Africa.
AB  - The advent of the polymerase chain reaction (PCR) coupled with the specificity of
      deoxyribocucleic acid (DNA)-DNA hybridization has led to the development of
      specific and sensitive molecular diagnostic tests to detect and characterize the
      organisms that cause theileriosis and heartwater. Theileriosis is a widespread
      disease of wild and domestic ruminants caused by apicomplexan parasites of the
      genus Theileria. Species-specific variations in small subunit ribosomal
      ribonucleic acid genes (SSUrRNA) have been used to develop probes that can
      distinguish between Theileria species such as T. parva, T. annulata, T. mutans,
      T. buffeli and T. taurotragi. Routine application of this test has led to the
      discovery of previously unknown species, such as Theileria sp. (buffalo) which is
      apparently apathogenic to both buffalo and cattle, and Theileria sp. (sable)
      which is pathogenic to sable and possibly also to roan antelope. In addition,
      characterization probes located in the internal transcribed spacer (ITS) can be
      used to distinguish between most isolates of the causative agents of East Coast
      fever (T. p. parva) and Corridor disease (T. p. lawrencei). Heartwater is an
      economically important disease of livestock and some wild ruminants, caused by
      the intracellular rickettsial parasite Ehrlichia (ex Cowdria) ruminantium. DNA
      probes used to detect and characterize E. ruminantium isolates include SSUrRNA
      (16S) probes, the pCS20 probe and map1 probes. A panel of eight 16S probes has
      been developed for the detection of E. ruminantium and related Ehrlichia species.
      There are probes for 5 different E. ruminantium genotypes, one which will detect
      all 5 of these genotypes, one to detect any Ehrlichia species other than E.
      ruminantium, and one for any Anaplasma species. The pCS20 probe is specific for
      E. ruminantium and is the most sensitive of the probes for E. ruminantium
      detection, but it is not able to distinguish among the different genotypes. The
      map1 gene has also been used for diagnosis, but the extensive polymorphism of
      this gene means that it is most useful for characterization of different
      genotypes of the parasite. Routine application of these tests has led to the
      discovery of new genotypes that are probably not E. ruminantium but are probably
      new species of Ehrlichia.

PMID- 12055843
TI  - Recent advances in molecular diagnostic techniques for human lymphatic filariasis
      and their use in epidemiological research.
AB  - Diagnosis of lymphatic filariasis for epidemiological studies is an area of
      science that has been greatly modernized over the last two decades. Recent
      developments and the introduction of new technologies have led to the replacement
      of traditional diagnostic methods that were insensitive, tedious and often
      impractical with molecular biology techniques that have considerable potential
      for field use. This paper reviews some of these major new techniques and the
      applications of molecular diagnosis in the field of lymphatic filariasis.

PMID- 12055844
TI  - DNA-based detection of onchocerca volvulus.
AB  - During the 1980s, the idea of using deoxyribonucleic acid probes for specific
      identification and diagnosis of infectious agents became very fashionable. There
      was therefore an explosion in the development of these tools and one particular
      group of organisms which received much attention was the parasitic nematodes.
      This review traces the development and use of such probes with the filarial
      nematode Onchocerca volvulus, with emphasis on their application to resolving
      certain 'problems' associated with this parasite, e.g. whether or not strains
      exist and difficulties in distinguishing the infective larval stage
      morphologically from related species.

PMID- 12055845
TI  - Application of single strand conformational polymorphism (SSCP) analysis with
      fluorescent primers for differentiation of Schistosoma haematobium group species.
AB  - To assess the utility of single-stranded conformational polymorphism (SSCP)
      analysis for the differentiation of schistosomes, using methods adapted for a
      Perkin Elmer ABI Prism 377 automated sequencer, 3 isolates of Schistosoma
      haematobium, 2 of S. intercalatum and single isolates of S. curassoni and S.
      bovis were selected for study. Two fluorescently labelled, double-stranded
      polymerase chain reaction products, amplified from the mitochondrial cytochrome
      oxidase subunit 1 (CO1) gene and the nuclear ribosomal second internal
      transcribed spacer (ITS2), were generated from single male and female worms.
      Changes in electrophoretic mobility of fragments within an SSCP profile revealed
      variation at individual, isolate and species levels. The mutational basis between
      representative SSCP profiles was confirmed by direct sequencing, demonstrating
      that single point substitutions were detectable. SSCP analysis has considerable
      potential as an alternative molecular method of identification and
      characterization of schistosomes. More broadly, fluorescence-based SSCP analysis
      is applicable to almost any gene target from any species of parasite and is a
      powerful molecular tool for genetic profiling.

PMID- 12055846
TI  - Differential diagnosis of Taenia saginata and Taenia solium infections: from DNA
      probes to polymerase chain reaction.
AB  - The objective of this work was the rapid and easy differential diagnosis of
      Taenia saginata and T. solium. First, a T. saginata size-selected genomic
      deoxyribonucleic acid (gDNA) library was constructed in the vector lambda gt10
      using the 2-4 kb fraction from the parasite DNA digested with EcoR1, under 'star'
      conditions. After differential screening of the library and hybridization
      analysis with DNA from T. saginata, T. solium, T. taeniaeformis, T. crassiceps,
      and Echinococcus granulosus (bovine, porcine, and human), 2 recombinant phages
      were selected. They were designated HDP1 and HDP2. HDP1 reacted specifically with
      T. saginata DNA, and HDP2 recognized DNA from both T. saginata and T. solium. The
      2 DNA probes were then sequenced and further characterized. HDP1 was a repetitive
      sequence with a 53 bp monomeric unit repeated 24 times in direct tandem along the
      1272 bp fragment, while the 3954 bp HDP2 was not a repetitive sequence. Using the
      sequencing data, oligonucleotides were designed and used in a polymerase chain
      reaction (PCR). The 2 selected oligonucleotides from probe HDP1 (PTs4F1 and
      PTs4R1) specifically amplified gDNA from T. saginata, but not T. solium or other
      related cestodes, with a sensitivity of < 10 pg of T. saginata gDNA, about the
      quantity of DNA in one taeniid egg. The 3 oligonucleotides selected from the HDP2
      sequence (PTs7S35F1, PTs7S35F2, and PTs7S35R1) allowed the differential
      amplification of gDNA from T. saginata, T. solium and E. granulosus in a
      multiplex PCR, again with a sensitivity of < 10 pg. These diagnostic tools have
      immediate application in the differential diagnosis of T. solium and T. saginata
      in humans and in the diagnosis of dubious cysts in the slaughterhouse. We also
      hope to apply them to epidemiological surveys of, for example, soil and water in
      endemic areas.

PMID- 12055847
TI  - The epidemiology of visceral leishmaniasis in east Africa: hints and molecular
      revelations.
AB  - Visceral leishmaniasis appears in the form of notoriously devastating epidemics
      and as an endemic disease of sporadic nature. In an attempt to understand the
      nature of this difference and its underlying causes, and to identify possible
      mechanisms for the instigation of outbreaks, the current status of the
      characterization of the parasite, its taxonomy, host immunity and genetics, are
      reviewed with the main focus on eastern Africa, one of the places where the
      dichotomous epidemiology of the disease is most pronounced. The new molecular
      tools offer various insights into the understanding of the complex epidemiology
      of visceral leishmaniasis and the interplay between parasite and host factors.
      Further insights are also provided on the parts played by demography, genetic
      history and geography in shaping the overall global portrait of the disease.

PMID- 12055848
TI  - Mechanisms of pathogenesis: differences amongst Leishmania species.
AB  - One of the features of the genus Leishmania is the diversity of tropism/disease
      resulting from infection. With notable exceptions, the form (visceral, cutaneous,
      diffuse cutaneous, mucocutaneous) and severity of disease is a function of the
      infecting Leishmania species together with host genetics and consequent
      inflammatory and immune responses. It has become evident from genetic and
      immunological studies using the murine model that the various members of the
      genus Leishmania differ in aspects of their 'approach' to the host immune system.
      We are just beginning to appreciate the complexities of these interactions, which
      have import for the development of a vaccine against leishmaniasis. In this
      paper, what is currently understood concerning the mechanisms of leishmanial
      pathogenesis (based upon studies employing the murine model) is briefly
      summarized.

PMID- 12055849
TI  - Polymorphism in the subtelomeric regions of chromosomes of Kinetoplastida.
AB  - Leishmania spp. and the related kinetoplastid Trypanosoma brucei are single
      celled parasites. In Leishmania, the nuclear genome comprises 36 diploid
      chromosomes and occasional amplified minichromosomes, while the T. brucei nucleus
      contains 11 larger diploid chromosomes and a variable number of intermediate
      sized and minichromosomes. This paper primarily describes the subtelomeric
      structure of the larger diploid chromosomes of L. major and T. brucei, although
      some aspects may also apply to smaller chromosomes. The diploid chromosomes
      contain most protein-coding genes and vary in size. The telomeric sequence is
      common to both species, but adjacent subtelomeric repeats vary between species
      and chromosomes. It is possible that some of the complex repeats described here
      play a role in stabilizing replication and copy number of the chromosomes. The
      subtelomeric regions of T. brucei chromosomes differ from those of other
      protozoan parasites, as they are dedicated to expression sites for variant
      surface glycoprotein genes, used by the parasite to evade immune destruction by
      antigenic variation. Variation in these sites creates segmental aneuploidy in
      many T. brucei chromosomes.

PMID- 12055850
TI  - Isolation and characterization of Leishmania infantum cDNA encoding a protein
      homologous to eukaryotic elongation factor 1 gamma.
AB  - This paper reports the isolation and characterization of a complementary
      deoxyribonucleic acid clone showing sequence homology with genes coding for the
      eukaryotic elongation factor 1 gamma (EF-1 gamma). The clone encodes an open
      reading frame of 404 amino acids corresponding to a deduced molecular mass of
      46.2 kDa. Database searches revealed 30-64% sequence identity between the
      Leishmania infantum EF-1 gamma and several eukaryotic homologues. Southern blot
      analysis indicated that 2 genes tandemly organized were present in the L.
      infantum genome. The 3' untranslated regions of these 2 genes differed in size.
      Southern hybridization and pulsed field gel electrophoresis showed that EF-1
      gamma genes are highly conserved among members of the Leishmania genus and must
      be clustered in a single chromosomal locus.

PMID- 12055851
TI  - Genes coding structural proteins in the Leishmania braziliensis complex.
AB  - Acidic ribosomal P1 and P2b proteins, referred to as P proteins, and histone H3
      are reported for first time in the Leishmania braziliensis complex.
      Deoxyribonucleic acid analysis and multiple sequence alignment suggest that both
      P proteins may maintain their structural function in the ribosomal stalk, in
      spite of the high rate of mutations detected. The deduced amino acid sequence of
      protein P1 showed 51% identity with Trypanosoma cruzi protein P1 and protein P2b
      showed 61% identity with T. cruzi protein P2b. Another conserved protein, L.
      (Viannia) braziliensis histone H3, showed 82% and 70% identity with histone H3 of
      L. (Leishmania) infantum and T. cruzi, respectively. The N-terminal end of this
      histone is divergent in comparison with the consensus eukaryotic sequence. Their
      predicted tridimensional structure was designed.

PMID- 12055852
TI  - Analysis of minicircle classes in Leishmania (Viannia) species.
AB  - This paper reports the analysis of minicircle sequence classes from 4 Leishmania
      species, all belonging to the 'New World' species of the subgenus Viannia:
      Leishmania braziliensis, L. guyanensis, L. panamensis and L. peruviana. A
      minicircle library was constructed for each species, and clones were analysed by
      restriction enzyme digest and sequence analysis. 319 minicircles from the 4
      species were examined and 96 of these were wholly or partially sequenced. The
      sequences of 41 whole minicircles--21 from L. panamensis, 8 from L. guyanensis
      and 6 each from L. braziliensis and L. peruviana are presented. Sequence classes
      were identified within which sequences were highly conserved, with only a small
      number of single base pair changes between them. In contrast, minicircles from
      different classes differed significantly, displaying sequence homology only over
      the minicircle conserved region. Some minicircle classes were identified which
      were shared between species. These minicircles displayed sequence variation which
      was potentially species-specific, and were analysed phylogenetically. These
      results question the hypothesis that minicircle sequence is rapidly evolving and
      also suggest that an as yet unknown selective pressure maintains sequence class
      conservation over the entire minicircle molecule even in different species, not
      only over the conserved region and the guide ribonucleic acid gene. A novel
      hypothesis is proposed to explain these results.

PMID- 12055853
TI  - Molecular markers for species identification in the Leishmania subgenus Viannia.
AB  - We have previously identified a novel genomic sequence of 500 bp, the beta 500
      DNA sequence, in the subgenus Leishmania (Viannia). This sequence was localized
      upstream of the beta-tubulin gene. Restriction fragment length polymorphism and
      hybridization analysis has shown that the beta 500-DNA sequence is specific to
      this subgenus. A polymerase chain reaction (PCR) assay confirmed this
      specificity. The beta 500-DNA sequence was apparently absent from the genomic
      deoxyribonucleic acid of L. colombiensis and L. equatoriensis. These results
      indicate that a PCR assay based on the beta 500-DNA sequence is likely to be of
      use to detect and identify Leishmania parasites of this subgenus in clinical
      samples with high sensitivity, specificity and reliability. The beta 500-DNA
      sequence can be considered a molecular marker for the subgenus Viannia.

PMID- 12055854
TI  - A kinetoplast DNA minicircle probe (B18) specific for the Leishmania subgenus
      Viannia.
AB  - This paper reports the development, sequence and specificity of probe B18, which
      hybridizes only to the kinetoplast deoxyribonucleic acid (kDNA) minicircle of
      Leishmania species of the subgenus Viannia. This probe was developed in 1985 and
      has been used extensively since, on whole kDNA, Leishmania dot-blots and kDNA
      minicircles amplified by the polymerase chain reaction.

PMID- 12055855
TI  - Homologous minicircles in Leishmania donovani.
AB  - Leishmania minicircular deoxyribonucleic acid (DNA) is arranged into different
      classes according to sequence. These classes differ substantially in sequence,
      despite species- and genus-specific regions, and are present in widely different
      copy numbers within and between Leishmania strains. Homologous minicircles have
      been identified in different species of Leishmania by comparing sequences of
      known minicircles. However, it is possible to select for minicircles of the same
      class by amplifying Leishmania DNA with polymerase chain reaction primers from
      the conserved and variable regions. This approach was used with 2 different
      minicircle classes in the L. donovani complex. In all isolates tested it was
      possible to amplify minicircles of the selected class.

PMID- 12055856
TI  - Molecular epidemiology and diagnosis of Leishmania: what have we learnt from
      genome structure, dynamics and function?
AB  - This paper reviews our exploration of the dynamics of the Leishmania genome and
      its contribution to epidemiology and diagnosis. We used as a model Peruvian
      populations of L. (Viannia) braziliensis and L. (V.) peruviana, 2 species very
      close phylogenetically, but phenotypically very different in biotope and
      pathology. We initially focused on karyotype analysis. Our data showed that
      chromosomes were subject to a fast rate of evolution, and were sensitive
      indicators of genetic drift. Therefore, molecular karyotyping appeared an
      adequate tool for monitoring (i) emergence of close species, (ii) ecogeographical
      differentiation at the intraspecific level, and (iii) strain 'fingerprinting'.
      Chromosome size variation was mostly due to the number of tandemly repeated genes
      (rDNA, mini-exon, gp63, and cysteine proteinase genes), and could involve the
      deletion of unique genes (L. (V.) braziliensis-specific gp63 families).
      Considering the importance of these genes in parasitism, their rearrangement
      might have functional implications: adaptation to different environments and
      pleomorphic pathogenicity. Our knowledge of genome structure and dynamics was
      used to develop new polymerase chain reaction (PCR) techniques. Amplification of
      gp63 genes followed by cleavage with restriction enzymes and study of restriction
      fragment length polymorphism (gp63 PCR-RFLP) allowed the discrimination of all
      species tested, even directly in biopsies with 95% sensitivity (compared with PCR
      amplification of kinetoplast deoxyribonucleic acid). At the intra-specific level,
      RFLP was also observed and corresponded to mutations in major immunogen domains
      of gp63. These seem to be under strong selection pressure, and the technique
      should facilitate addressing how the host's immune pressure may modulate parasite
      population structure. Altogether, gp63 PCR-RFLP represents a significant
      operational improvement over the other techniques for molecular epidemiology and
      diagnosis: it combines sensitivity, discriminatory power and prognostic value.

PMID- 12055857
TI  - Distinguishing Leishmania tropica and Leishmania major in the Middle East using
      the polymerase chain reaction with kinetoplast DNA-specific primers.
AB  - This paper reports attempts to develop a sensitive and inexpensive procedure for
      rapid diagnosis of cutaneous leishmaniasis at the species level using skin
      scrapings from patients. The presence of 3 species (Leishmania major, L. tropica
      and L. infantum) in Israel and the West Bank demonstrates the need for a species
      specific detection method in this region. The primer pair Uni21/Lmj4 was
      developed on the basis of an L. major minicircle sequence but it also amplified
      other 'Old World' species of Leishmania. Due to species-specific differences in
      the size of minicircles, these primers can be used in the polymerase chain
      reaction to answer diagnostic and epidemiological questions.

PMID- 12055858
TI  - Evolutionary genetics and molecular diagnosis of Leishmania species.
AB  - An extensive study has been performed on various natural populations of
      Leishmania from the 'Old' and 'New Worlds' using multilocus enzyme
      electrophoresis and random amplification of polymorphic deoxyribonucleic acid.
      The data are interpreted in evolutionary genetic terms in order to give a firm
      basis to studies dealing with the relevant medical properties of pathogens. We
      confirm that Leishmania undergoes clonal evolution with occasional phenomena of
      hybridization. This suggests that the microorganism genotypes are stable in space
      and time and consequently have epidemiological and medical relevance. It is
      crucial to have a clear definition of the taxa to be identified. In the case of
      Leishmania, there is at present no firm consensus on the species concept. We
      propose that any new species of Leishmania should correspond to a 'discrete
      typing unit' that exhibits specific medical and/or epidemiological characters.
      Based on this approach, the species status of L. peruviana can be supported. On
      the contrary, L. panamensis cannot be clearly distinguished from L. guyanensis.
      Our studies on the genetic diversity of Leishmania show that a given stock is not
      representative of the genus, the subgenera, or any species. We suggest that the
      genetic polymorphism of Leishmania has a strong impact on the parasite's
      biomedical properties.

PMID- 12055860
TI  - Be good as gold--buy green.

PMID- 12055861
TI  - Happier nurses means better care.

PMID- 12055859
TI  - Molecular epidemiology of Leishmania infantum on the island of Majorca: a
      comparison of phenotypic and genotypic tools.
AB  - In the Mediterranean basin, Leishmania infantum is the causative agent of both
      visceral and cutaneous leishmaniasis, and is an important opportunistic parasite
      in patients infected with human immunodeficiency virus (HIV). The commonest
      method used to study the variability of Leishmania spp. is isoenzyme analysis. In
      addition to this, we employed 3 assays based on the polymerase chain reaction
      (PCR): random amplified polymorphic deoxyribonucleic acid (RAPD), intergenic
      region typing (IRT), based on the amplification of ribosomal ribonucleic acid
      internal transcribed spacers and restriction fragment length polymorphism (PCR
      RFLP). We used 54 L. infantum stocks isolated from HIV co-infected patients, 38
      isolated from dogs, 3 isolated from immunocompetent patients and 3 isolated from
      1826 sand files in the island of Majorca (Spain), a closed ecological niche.
      Zymodemes MON-1 (70%), MON-24 (11%) and MON-34 (18%) were found among the human
      isolates, and MON-1 (95%) and MON-108 (5%) among those from dogs. RAPD and IRT
      could not discriminate among the strains as they all gave the same pattern, even
      when different zymodemes were examined. In contrast, PCR-RFLP was able to
      distinguish the strains and, furthermore, a dendrogram (unweighted pair group
      method with arithmetic average [UPGMA]) was constructed from the genetic
      distances derived from RFLP data. The Leishmania isolates from HIV-infected
      subjects formed a single cluster, supporting the existence of an artificial
      anthroponotic cycle previously proposed by our group, in which syringes have been
      substituted for sand flies, and in which certain clones have been spread among
      intravenous drug users. This contrasts with the clusters representing a zoonotic
      cycle, involving dogs, sand flies and both immunocompetent and immunocompromised
      humans.

PMID- 12055862
TI  - Nursing skill mix and experience reduce patient mortality.

PMID- 12055863
TI  - Improving the management of waiting lists for elective healthcare services:
      public perspectives on proposed solutions.
AB  - An innovative approach to managing waiting lists and access to elective care, and
      one that is more fair and consistent with the 'guarantee of access' as stipulated
      in the Canada Health Act, has been developed by a partnership of medical
      associations, provincial ministries of health, regional health authorities and
      research centres. Operating as the Western Canada Waiting List Project, this
      group has developed beta versions of waiting list prioritization tools in five
      problematic clinical areas: hip and knee joint replacement; cataract removal
      surgery; general surgery; children's mental health services; and MRI scanning.

PMID- 12055865
TI  - Creating a surgical wait list management strategy for Saskatchewan.
AB  - In the summer of 2001, Saskatchewan Health asked Dr. Peter Glynn, Health Care
      Consultant, Dr. Mark Taylor, the Deputy Head of General Surgery at St. Boniface
      General Hospital in Winnipeg and Dr. Alan Hudson, a Toronto-based neurosurgeon
      and former CEO of the University Health Network, to advise on the creation of a
      provincial surgical wait list management strategy to address growing concerns
      about waiting times for many non-emergent surgical procedures. Although the work
      was focused on Saskatchewan, this is a common issue across the country.

PMID- 12055864
TI  - How do patients and physicians rate urgency of care? A comparison of urgency
      ratings for general surgery.
AB  - The notion of uniform terms and conditions speaks to equity of access--that fair
      rules apply in obtaining medically necessary services. However, when demand for
      medical services outweighs the supply of these services, the issue of "fair
      rules" concerning who comes first or who is most in need is a hotly debated
      subject. This debate has focused not just on how long patients may have to wait
      for access, but also on the question of how caregivers decide the priority of
      providing care. Central to this discussion is the need to develop a transparent
      methodology that fairly prioritizes patients based on urgency; timely access to
      services and acceptability to all stakeholders.

PMID- 12055866
TI  - It's high time for hospitals to adopt private sector marketing strategies.
AB  - To ensure ongoing and increased public support, healthcare institutions need to
      adopt strategies that will help them get their message to key target audiences.
      How well they play the marketing game can have a major impact on everything from
      funding levels to recruitment to public as well as government perception and
      support.

PMID- 12055867
TI  - Keeping our eyes on the four key challenges.

PMID- 12055868
TI  - A toolkit to facilitate the implementation of clinical practice guidelines in
      healthcare settings.
AB  - In the early stages of development and pilot implementation of the guidelines, it
      became apparent that organizations were struggling to identify ways to introduce
      and implement the guidelines. The majority of the pilot sites were providing
      education sessions to facilitate CPG utilization with little attention to other
      implementation strategies. Those charged with introducing the CPG into the
      clinical setting were soon faced with a myriad of implementation challenges for
      which they needed a solution. It became clear that a planned systematic approach
      to facilitate implementation of CPGs was needed.

PMID- 12055869
TI  - Registered Nurses Association of Ontario's best practice guideline as a tool for
      creating partnerships.
AB  - The Best Practice Guidelines project has been instrumental in facilitating a
      partnership between an acute care community hospital and two long-term care
      facilities in northwestern Toronto. This article outlines the challenges
      experienced in the acute care community hospital in developing partnerships, not
      just with the two long-term care facilities, but also within the organization.
      This article also offers insight into the strategies used to overcome the
      challenges and to support the implementation of the guideline at point of care.

PMID- 12055870
TI  - Nursing Best Practice Guidelines: a gift for advancing professional practice in
      every environment.
AB  - How patients experience out healthcare system is driven to a large extent by the
      excellence and consistency of standards in nursing practice. Best Practice
      Guidelines offer a bridge, that combined with organizational and professional
      commitment, can facilitate the goal of supporting knowledge workers.

PMID- 12055871
TI  - A collaborative evidence-based approach to making healthcare a healthier place to
      work.
AB  - It is increasingly well documented that a collaborative problem-solving approach
      is more effective in addressing workplace health concerns than an adversarial
      approach. Combining this with strategies based on good evidence is key to
      success. On this premise, a trial was conducted in British Columbia, beginning in
      July 1999, based on a collaborative approach in which healthcare workers and
      managers work together to identify and implement evidence-based initiatives to
      improve the health and working conditions of healthcare workers.

PMID- 12055872
TI  - Profile: Dr. Noni MacDonald. Interview by Cynthia Martin.

PMID- 12055873
TI  - Patients find success haggling as health-care costs climb.
AB  - In small but growing numbers, Americans are taking an innovative approach to
      controlling health-care costs: They're haggling with their doctors. Fed up with
      mounting health bills, consumers ae getting as much as 30% off everything from
      eye exams to fertility procedures just by agreeing to pay upfront. Others are
      holding their doctors over a barrel by waiting a few months to pay the bill.
      Already, a new cottage industry of middlemen who negotiate healthcare bills for
      patients report their haggling business is up as much as 25% in the last two
      years.

PMID- 12055874
TI  - Implementing an evaluation research and accountability-driven system for juvenile
      justice education in Florida.

PMID- 12055875
TI  - Integrating research, policy, and practice in juvenile justice education.
AB  - This article provides an overview of the history and context leading to Florida's
      efforts to implement an evaluation-driven research and associated quality
      assurance system for its juvenile justice education policies and practices. The
      Juvenile Justice Educational Enhancement Program began implementing Florida's
      evaluation research and quality assurance system to juvenile justice education in
      1998. The article includes a brief summary of articles comprising this special
      issue of Evaluation Review that address the Juvenile Justice Educational
      Enhancement Program's various functions, methodological components, data,
      preliminary findings, continuing evaluation research efforts, and impediments.

PMID- 12055876
TI  - Evaluation research and quality assurance.
AB  - This article describes the Juvenile Justice Educational Enhancement Program's
      implementation of an evaluation research-driven quality assurance process for
      Florida's juvenile justice educational programs. The article reviews the prior
      literature on promising juvenile justice educational practices and describes the
      educational quality assurance standards and annual modifications that draw from
      these promising practices. Included is description of the associated quality
      assurance, technical assistance, and corrective action processes that are used in
      the effort to ensure quality and accountable juvenile justice education. Quality
      assurance is argued to be a fundamental and necessary component to both the
      Juvenile Justice Educational Enhancement Program's evaluation research and
      accountability functions.

PMID- 12055877
TI  - Correlates of quality educational programs.
AB  - Preliminary evaluation findings are presented that explore relationships between
      educational program quality and program characteristics such as program type,
      security level, aftercare, teacher certification, facility size, and private
      versus public provider. Several program characteristics are found to be related
      to measurements of educational program quality. Among the major quality
      characteristics are proportion of program teachers that are professionally
      certified, smaller sized facilities versus larger facilities, level of aftercare
      services, and provider sources, with private for-profit providers being the
      lowest performing and public providers being the highest performing. The article
      closes with description of the Juvenile Justice Educational Enhancement Program's
      continuing evaluation of correlates to educational program quality through the
      continued development of a comprehensive database.

PMID- 12055878
TI  - Pre-, post-, and longitudinal evaluation of juvenile justice education.
AB  - This article describes two stages of the Juvenile Justice Educational Enhancement
      Program's pre-, post-, and longitudinal evaluation research. Pilot studies were
      used to explore how to design statewide research of pre- and postassessment
      scores and community reintegration outcomes. Preliminary findings suggest that
      higher performing educational programs produce greater educational gains as
      measured by academic achievement tests, credits earned, and pupil progression
      rates. The findings also indicate that these programs have more students
      returning to school and lower recidivism rates. Building on the pilot studies,
      refinements were made to the research designs to enable more comprehensive
      statewide evaluation. Current research includes collection of pre- and
      postassessment scores from official sources on approximately 16,000 juvenile
      justice youths. In addition, a research design has been developed to examine
      program effectiveness by measuring community reintegration variables. Multiple
      data sources, including official and self-reported data on family, school,
      employment, and subsequent crime involvement, will be used in the longitudinal
      study.

PMID- 12055879
TI  - Data integration in the evaluation of juvenile justice education.
AB  - This article discusses the Juvenile Justice Educational Enhancement Program's
      evaluation of juvenile justice education through the integration of multiple data
      sources. Validation of best practices and the corresponding effect of these
      practices on community reintegration require the development of a comprehensive
      database of program-level and individual-level indicators from several sources.
      These sources include the Florida Department of Education, the Florida Department
      of Juvenile Justice, the Florida Department of Law Enforcement, the Florida
      Department of Corrections, and the Juvenile Justice Educational Enhancement
      Program's own educational quality assurance and pre-/posttest data. This article
      examines the methodological, political, and bureaucratic obstacles encountered in
      this effort. Evaluation research analyses are also explored with an emphasis on
      the meaning of outcome measures relative to causal issues of time order, the
      modeling of events, and analytic strategy. The article provides a framework for
      future juvenile justice educational evaluation and a critical examination of
      problems encountered in integrating data sources for the purpose of outcome
      evaluation.

PMID- 12055880
TI  - Evaluation research, policy, and politics.
AB  - This article discusses the role of politics in the Juvenile Justice Educational
      Enhancement Program's effort to use evaluation research data to inform Florida's
      juvenile justice education policies and practices. Through consideration of the
      Juvenile Justice Education Enhancement Program's experiences with privatization
      and the tough love and economy of scale rationales for larger and more custodial
      juvenile institutions, the variable role of politics is examined. Although the
      two examples are different, the discussion demonstrates that by maintaining an
      overriding commitment to its evaluation research purpose, the Juvenile Justice
      Educational Enhancement Program has been able to continue its data-driven policy
      efforts despite operating in a politically charged environment.

PMID- 12055888
TI  - Nursing on the move. Ready for Texas with a response plan.

PMID- 12055889
TI  - Scheme helps build achievement recognition.

PMID- 12055890
TI  - Opting for new central plant.
AB  - A major healthcare sector project involving the supply of chilled water, steam
      and emergency power for facilities in Queensland, Australia, is detailed in this
      article. The review was prepared by Donald Glynn, energy manager/plant
      operations, Royal Brisbane Hospital.

PMID- 12055891
TI  - Outsourcing can have great appeal.
AB  - Build, own, operate; energy performance contracting; asset acquisition and
      management. These are among latest trends in energy and facilities management.
      What they mean and how they apply to the health sector are subjects addressed in
      this article, which is based on an International Federation of Hospital
      Engineering Congress paper presented by Martin Turner, of Australia, for AGL
      Limited.

PMID- 12055893
TI  - Designing for a safe workplace.
AB  - X-radiation is an intense form of energy which occurs naturally as a background
      force and which is also produced artificially. Used in medicine, it offers
      valuable assistance in diagnosis and therapy--but there is a risk which must not
      be forgotten. Unfortunately there is no simple formula to calculate if radiation
      is dangerous or safe, says Wardray Premise Limited. In some instances a single
      dose will induce the growth of cancerous cells. In other instances dosage 100
      times greater will have no apparent effect.

PMID- 12055892
TI  - Boosting morale--and productivity.
AB  - In a field such as healthcare facility management where technology is changing
      all the time, training is critical, says James O. Wear, Ph D, of the USA. This
      article is based on an International Federation of Hospital Engineering Congress
      paper.

PMID- 12055894
TI  - New ovens are a boon.
AB  - Liz Ehlers is extremely impressed with Rational CPC combi ovens. Head of catering
      at Frenchay Hospital in Bristol, she is responsible for feeding up to 550
      patients each day. Together with visitors and staff in the hospital's restaurants
      as well as satellite units, there can be a demand for 2,500 hot meals a day.

PMID- 12055895
TI  - Interview with Rupert Evans, Sr., FACHE, president, Institute for Diversity in
      Health Management. Interview by Kyle Grazier.

PMID- 12055896
TI  - Case management: a serious solution for serious issues.

PMID- 12055897
TI  - The nursing shortage: why is it happening?

PMID- 12055898
TI  - Eliminating the disparities in treatment: the link to healing a nation.

PMID- 12055899
TI  - Managing the workforce reduction: hospital CEO perceptions of organizational
      dysfunction.
AB  - Over the past few years many nations have undertaken activities aimed at
      restructuring and reengineering their health system as a means of achieving
      greater cost effectiveness and consumer responsiveness. Most efforts at reforming
      healthcare delivery have been accompanied by the downsizing of healthcare
      organizations. Organizations that are undergoing decline or significant workforce
      contractions are widely believed to experience a number of negative or
      dysfunctional attributes as a consequence of reductions in, or redeployments of,
      their labor force. For organizations undergoing planned workforce reductions,
      much speculation has been made in an attempt to identify a set of "best
      practices" that have the potential to mitigate the dysfunctional consequences
      associated with large permanent reductions in the workforce. This article
      explores the relationships among workforce-reduction practices and perceptions of
      organizational dysfunction in a large sample of Canadian hospitals. Results of
      the analysis suggest that the application of certain "progressive" workforce
      reduction practices preceding, during, and subsequent to the downsizing process
      may play an important role in mitigating some of these dysfunctional
      organizational consequences. This research provides some evidence to suggest that
      how a workforce reduction is carried out may have a greater effect on
      organizational effectiveness than either the magnitude or severity of the overall
      workforce reduction.

PMID- 12055900
TI  - Applying the balanced scorecard in healthcare provider organizations.
AB  - Several innovative healthcare executives have recently introduced a new business
      strategy implementation tool: the Balanced Scorecard. The scorecard's measurement
      and management system provides the following potential benefits to healthcare
      organizations: It aligns the organization around a more market-oriented, customer
      focused strategy It facilitates, monitors, and assesses the implementation of the
      strategy It provides a communication and collaboration mechanism It assigns
      accountability for performance at all levels of the organization It provides
      continual feedback on the strategy and promotes adjustments to marketplace and
      regulatory changes. We surveyed executives in nine provider organizations that
      were implementing the Balanced Scorecard. We asked about the following issues
      relating to its implementation and effect: 1. The role of the Balanced Scorecard
      in relation to a well-defined vision, mission, and strategy 2. The motivation for
      adopting the Balanced Scorecard 3. The difference between the Balanced Scorecard
      and other measurement systems 4. The process followed to develop and implement
      the Balanced Scorecard 5. The challenges and barriers during the development and
      implementation process 6. The benefits gained by the organization from adoption
      and use. The executives reported that the Balanced Scorecard strategy
      implementation and performance management tool could be successfully applied in
      the healthcare sector, enabling organizations to improve their competitive market
      positioning, financial results, and customer satisfaction. This article concludes
      with guidelines for other healthcare provider organizations to capture the
      benefits of the Balanced Scorecard performance management system.

PMID- 12055902
TI  - The staffing crisis.
AB  - It's not just a matter of hiring more nurses: hospital leaders need to make human
      resources a priority--and fast. The situation cries out for strategic decisions
      that will benefit workers as well as patients.

PMID- 12055901
TI  - Comparison of specialty referral patterns of primary care providers.
AB  - Difficulty, perceived by 17 treatment facilities, of obtaining specialty referral
      appointments at Dwight David Eisenhower Army Medical Center (DDEAMC), a major
      referral center, prompted this study that utilizes provider profiling as a tool
      to answer three questions that examine the problem: (1) Is the difficulty in
      obtaining referral appointments real or perceived? (2) Are the referral patterns
      of the providers contributing factors in the perceived inability to meet the
      demand for specialty appointments? (3) If the providers' referral patterns are a
      contributing factor, which provider behaviors need to be modified? Major findings
      of the study included: 1. the referral rate of the primary care providers was 8
      percent, compared to the national average of 7.5 percent; 2. interns and
      residents were provider outliers with referral rates of 11.7 percent and 13.5
      percent, respectively; and 3. of the 32,182 referral appointments requested
      during Fiscal Year 1999, slightly less than 2.4 percent were disengaged. Data
      analysis indicates opportunities for improvement of referral rates in DDEAMC's
      department of primary care by addressing the referral practices of residents and
      interns, which will therefore decrease the number of disengaged patients. By
      decreasing the number of referrals, the organization will more effectively
      control internal costs in an era of shrinking budgets.

PMID- 12055903
TI  - Frank Ostaseski. Interview by Joe Flower.
AB  - The founder of the Zen Hospice Project talks about living and dying. Many
      hospitals, he says, have progressive programs that help their employees,
      patients, and family members reduce their stress.

PMID- 12055904
TI  - Engaging the staff.

PMID- 12055905
TI  - The bioethics program.

PMID- 12055906
TI  - The spirit of craftsmanship. Excellent results come from pride in work.

PMID- 12055907
TI  - New White House report. Commission supports scientific research on CAM.

PMID- 12055909
TI  - The median and the edge. We need to distinguish between the future that's arrived
      and the future that may never come.

PMID- 12055908
TI  - Communication, standards, and technology. HCA creates a new system to reduce
      medical errors.

PMID- 12055910
TI  - Putting people first.

PMID- 12055911
TI  - Safety throughout the hospital.

PMID- 12055912
TI  - Still crazy after all these years.

PMID- 12055913
TI  - Corporate finance is not a bad word. Using complex financial tools that are sound
      and prudently applied is still a smart approach to managing capital.

PMID- 12055914
TI  - Case study: 1. Ascension. Rising to change.

PMID- 12055916
TI  - Case study: 3. Kaiser. Off-balance (sheet) maneuver.

PMID- 12055915
TI  - Case study: 2. Heartland. Swapping strategies.

PMID- 12055917
TI  - Health care finance goes corporate. Nonprofit systems are being forced to grow
      more financially savvy--though Enron may deter some innovation.

PMID- 12055919
TI  - [Medical demographic trends in the Volga region during recent decade].
AB  - Time course of demographic processes in the Volga region has been studied. The
      unfavorable demographic situation manifests by decreased number of children and
      increased number of subjects of incapable age, decreased birth rate, increased
      mortality, formation of the negative natural increment. Decreased number of
      children and increased number of retired subjects aggravates the demographic
      loading of the capable population. This inevitably leads to negative economic
      demographic consequences.

PMID- 12055920
TI  - [Population health protection at territories contaminated after the Chernobyl
      accident].
AB  - A concept of preserving population health at territories contaminated after the
      Chernobyl accident is proposed, which is based on the results of multifactorial
      evaluation of relationships and prognostic evaluations of the basic medical
      demographic parameters.

PMID- 12055921
TI  - [Morbidity and reproductive health of female students of higher school].
AB  - The studies demonstrated a low level of somatic and reproductive health of female
      students. An increase of morbidity was recorded during recent 3 years, with
      specific characteristics in each age groups. An unfavorable model of reproductive
      and sexual behavior is characteristic of students in general. Under present
      conditions, the authors emphasize the priority trend of family planning service
      in work with young people, specifically with students as a population
      representing the economic, working, and reproductive potential of the country.

PMID- 12055922
TI  - [Medical demographic characteristics of long livers of the Bashkortostan
      Republic].
AB  - Results of comprehensive studies of medico-social problems of long-living
      subjects in the Bashkortostan Republic are presented. The number of subjects aged
      over 90 years, particularly male, notably increased during the recent decade. The
      family and marital status of long-livers is characterized. Virtually all of them
      had families and children, often more than 3; by the moment of the study they
      lived with children or grandchildren and were active, their life style
      corresponding to their age and physical status.

PMID- 12055923
TI  - [The status and prospects of public health monitoring].

PMID- 12055925
TI  - [Major trends in personnel selection in the regional public health system].
AB  - Optimization of public health staff provision cannot be solved from the viewpoint
      of quantitative criteria. Processes running in this system are associated with
      changes in organization, technological, financial mechanisms and will inevitably
      lead to changes in the staff policy.

PMID- 12055924
TI  - [Status and time course of infant health].

PMID- 12055926
TI  - [Organizational and technological problems in the adherence to the patient's
      rights].
AB  - Presents one of the most pressing and least studied problems: patient's right
      protection in medicine and approaches to solution of this problem. Outlines the
      main approaches to improving the state of the problem and some organizational and
      technological aspects. The author emphasizes the need in development of universal
      standard documents at a federal level, which will help develop a universal
      strategy in development of the system of patient's right protection.

PMID- 12055927
TI  - [Current problems of the organization of specialized medical services for rural
      population].

PMID- 12055928
TI  - [Stages of medical rehabilitation of patients in therapy].
AB  - Organization of staged medical rehabilitation of therapeutic patients is
      discussed. Use of rehabilitation methods at the stages of outpatient clinic,
      hospital, and sanatorium is discussed. Validation of the health improving effects
      of these measures is given. Conceptual substantiation of differentiation of
      rehabilitation stages by the specific features of rehabilitative measures is
      presented.

PMID- 12055929
TI  - [Issues of healthy life style in the professional preparation of the physician].
AB  - The main value orientations of medical students are directly or indirectly
      associated with various components of health. On the other hand, the knowledge of
      the predominating effect of life style on health, hazards of nicotine and alcohol
      did not become a persuasion in the majority of students, and high value of health
      did not transform into motivation forits preservation. That is why special
      attention in the training of physicians should be paid to the formation of
      practical habits of fundamentals of healthy life style. Healthy life style, an
      obligatory component of professional status of a physician, promotes a higher
      general cognitive activity of students and formation of persuasion of future
      doctors in their obligatory personal involvement in the solution of the problem
      of healthy life style of the entire population.

PMID- 12055930
TI  - [The state medico-social insurance in Russia: retrospectively and at the present
      time].

PMID- 12055931
TI  - [Problems in municipal public health financing].

PMID- 12055932
TI  - [Life devoted to cardiosurgery (80th anniversary since V.I. Burakovski's birth)].

PMID- 12055933
TI  - [Preparation and introduction of the Code of St. Vladimir University (Kiev),
      1842. Report I. Beginning the preparation of the Code of St. Vladimir University
      (Kiev), 1842].

PMID- 12055934
TI  - [Landmarks in the development of the science of hypoxia].

PMID- 12055935
TI  - [Health personnel in Provisional Government].

PMID- 12055936
TI  - [The creation of the military medical service in Russia].

PMID- 12055937
TI  - [Historical dates and anniversaries in the history of medicine in 2002].

PMID- 12055938
TI  - [Medical demographic problems in improvement of population health in Siberia].
AB  - Time course of population mortality in Siberia in 1985-1999, mean life span of
      men and women, major mortality causes in the neonatal and capable age are
      presented. Population health loss resultant from mortality, morbidity, and
      disability is evaluated.

PMID- 12055939
TI  - Measuring the size of ulcers by planimetry: a useful method in the clinical
      setting.
AB  - OBJECTIVE: The aim of this study was to compare four measurement methods. Digital
      planimetry was compared with mechanical planimetry, placing the film over graph
      paper and counting the squares (grid tracing), and multiplying the two maximal
      perpendicular diameters of the ulcer (diameter product). METHOD: Twenty patients
      with 50 chronic leg ulcers of various aetiology and sizes (20 ulcers were < or =
      3 cm2, 15 ulcers were > 3 cm2 and < or = 10 cm2, and 15 ulcers were > 10 cm2)
      were enrolled consecutively into this study. Ulcer area was calculated from film
      transparency tracings using a digital planimeter, a mechanical planimeter, grid
      tracing and diameter product. RESULTS: The mean difference of digital planimetry
      versus mechanical planimetry, grid tracing and diameter product was 0.51 cm2,
      0.72 cm2 and -5.38 cm2, respectively. For all methods difference tended to
      increase with ulcer size. CONCLUSION: Digital and mechanical planimetry, together
      with grid tracing, appear to be appropriate means of obtaining accurate surface
      area measurements. Digital planimetry is a quick and practical method and could
      therefore be recommended in the clinical setting.

PMID- 12055940
TI  - Hot sand burns on the sole of a patient with diabetes.
AB  - A patient with diabetes who burnt his feet by walking on hot sand was treated
      with an amorphous hydrogel, which resulted in full wound healing within four
      weeks. These patients should avoid walking barefoot on sand whenever possible.

PMID- 12055941
TI  - Silver. 2: Toxicity in mammals and how its products aid wound repair.
AB  - The second article examining the role of this metallic element in a wound
      environment discusses toxicity in individual cells, animals and humans and
      considers how different silver-based dressings assist in wound healing.

PMID- 12055942
TI  - Learning to face the unthinkable. The charity Changing Faces celebrates 10 years
      of campaigning.

PMID- 12055943
TI  - The role of graftskin (Apligraf) in difficult-to-heal venous leg ulcers.
AB  - A relatively recent option for treating leg ulcers that have lasted longer than a
      month is to use living bilayered skin equivalent alongside cornerstone
      compression therapy. This article discusses Graftskin and considers its practical
      use.

PMID- 12055944
TI  - The effect of varying cuff position on recording ankle systolic blood pressure.
AB  - OBJECTIVE: Ankle brachial pressure index (ABPI) aids the diagnosis of leg ulcer
      aetiology, although there is potential for patient anxiety or discomfort when the
      cuff is placed over an ulcerated ankle. This study aimed to ascertain any
      differences in systolic pressure if the cuff is positioned proximal to the ankle
      and to determine the feasibility of varying the cuff position to avoid ulcerated
      areas. METHOD: The systolic blood pressure in the lower limbs of healthy
      volunteers (n = 60) was measured with the cuff at two discrete sites on the lower
      limb. RESULTS: There was a statistical difference in systolic blood pressure
      readings between the two sites (0-4 mmHg; p = 0.02) and a statistically
      significant ABPI difference (-0.08 to 0.05; p < 0.002). CONCLUSION: Blood
      pressure recording is subject to considerable variation in clinical practice and
      the ABPI has to vary by more than 0.15 to be clinically significant. Therefore,
      the differences in systolic pressure between sites and the ABPI calculations are
      not clinically significant in this study. An additional finding was that some
      subjects found the upper cuff position uncomfortable during the procedure.

PMID- 12055946
TI  - Venous leg ulcer recurrence: prevention and healing.
AB  - After a leg ulcer has healed, well-fitting compression stockings, patient
      education and regular check-ups are the basis for preventing recurrence. This
      article examines patterns in recurrence and subsequent healing among patients at
      an ulcer clinic.

PMID- 12055945
TI  - Insight into the development of non-adherent, absorbent dressings.
AB  - OBJECTIVE: This study aimed to develop a variety of wound dressing materials,
      made from standard natural fibres, that have high absorption and non-adherent
      characteristics. METHOD: A total of 21 dressings were made using knitted and
      crochet technologies and their absorbency was tested. Five non-adherent recipes
      were selected from a range of chemical formulations and the optimised non
      adherent finishes were applied to the four best dressings. Their absorbency and
      non-adherent properties were evaluated. RESULTS: The study demonstrated that rib
      cotton (RC), rib viscose (RV), crochet cotton medium (CCM) and crochet viscose
      medium (CVM) dressings possess high absorption and that five finishing recipes, C
      + D, A + G, I, I + N and I + G, impart high absorption as well as non-adherent
      properties. The finish I + G is superior in imparting non-adherence to RV
      dressing, both in dry and moist conditions. This means that irrigation with
      water, saline or sodium citrate solution before removing the dressing from a
      wound is not needed. CONCLUSION: A number of novel knitted and crochet structures
      with enhanced absorbency have been designed for wound management using standard
      bleached fibres. Novel non-adherent finishes for the developed structures have
      been formulated for the developed dressings, and offer an alternative to existing
      non-adherent dressings.

PMID- 12055948
TI  - Satisfaction higher for physician executives who treat patients, survey finds.
AB  - If you're satisfied with your physician executive job, one factor contributing to
      your happiness may be that you're still seeing some patients. Check out the
      results of a national survey that examines why some physician executives are more
      satisfied with their jobs.

PMID- 12055947
TI  - Money management, patient safety and customer service among top concerns for
      physician executives. Interview by Barbara Linney.
AB  - Find out what's happening today and what the future may be like for physician
      executives. Seasoned physician executives and well-known physician executive
      recruiters share their insights on the profession.

PMID- 12055949
TI  - Service and collaboration keys to physician control.
AB  - Discover what physicians must do to regain power and half health care's slide
      from a profession toward a trade. The solutions lie in better customer service
      and improved physician collaboration.

PMID- 12055950
TI  - Plague, pressure and politics part of life for CDC leader. How Koplan coped with
      the anthrax outbreak, and a look at his rise to the top. Interview by Maryn
      McKenna..

PMID- 12055951
TI  - Why doctors are afraid of numbers.
AB  - Physicians are said to be data-driven. However, their behavior frequently is at
      odds with this belief. Physicians often protest when presented with unfavorable
      data, complaining that the data are not applicable to them. Take a look behind
      this behavior.

PMID- 12055953
TI  - Is the business of health care hurting the profession?

PMID- 12055952
TI  - Cultivate your core competencies.
AB  - Your core competencies make you much more valuable to your organization. Find out
      ways to nurture and promote those competencies.

PMID- 12055954
TI  - The psychological contract: retaining newly employed physicians.
AB  - You spend lots of time and money recruiting the best candidates to fill your
      physician positions. But sometimes you lose those physicians after only a year or
      two on the job. Discover ways to help stop the turnover and keep valued employees
      happy.

PMID- 12055955
TI  - Divesting losers: chipping away at integrated delivery systems.
AB  - Integrated health systems are rapidly divesting earlier acquisitions to beef up
      their bottom lines. Take an in-depth look at what the future may hold as the
      health systems battle to reorganize and reap greater profits.

PMID- 12055956
TI  - Determining physician compensation--Part II.

PMID- 12055957
TI  - Maximize physician productivity with better workflow.

PMID- 12055958
TI  - Making the most of your career--and your life.
AB  - Take a look at a simple way to evaluate your job. Start figuring out how to take
      on more tasks that you like and get rid of those you dislike.

PMID- 12055959
TI  - Act outlines ways to protect health care workers and the public in an emergency.
AB  - In case of emergency, state public health officials need to be ready and
      authorized to act. Here's an overview of the Model State Emergency Health Powers
      Act and the powers it provides.

PMID- 12055960
TI  - Society's values, fears support health care's noble cause.

PMID- 12055961
TI  - Neurologic disease in HIV-1 infected children.

PMID- 12055962
TI  - Understanding drug-drug interactions in the management of HIV disease.

PMID- 12055963
TI  - Depression can be a serious problem for HIV infected.

PMID- 12055964
TI  - Study: HIV+ people often don't disclose status to sex partners.

PMID- 12055965
TI  - How should nutrition goals change in end-of-life care?

PMID- 12055966
TI  - Some dental professionals still reluctant to treat HIV patients.

PMID- 12055967
TI  - Yalom's book attempts to mentor new generation of therapists.

PMID- 12055968
TI  - Will Louisiana's new consent statues be helpful to clinicians?

PMID- 12055969
TI  - Media dramatize need for center. Oregon friends rally for burn center remodeling
      cause.
AB  - A carefully orchestrated fund-raising and media relations campaign contributed to
      the opening earlier this year of the new Oregon Burn Center on Legacy Health
      System's Emanuel Hospital campus, Portland, Ore. The new $5 million center is the
      only facility of its kind between Sacramento, Calif., Salt Lake City and Seattle.
      It replaces the original 12-bed facility built in 1973. The expanded center has
      16 beds in 16 private rooms, treatment areas designed for children and a host of
      other state-of-the-art improvements that make the Oregon Burn Center among the
      nation's finest. Between Legacy's investment of $3 million and contributions from
      Oregonians, more than $5 million was raised for the new center. Beyond that,
      annual giving, which amounted to $85,000 in fiscal 2001, is holding steady in
      2002.

PMID- 12055970
TI  - New communications strategy insures hospital system's future.
AB  - According to Ron Shinkman, a veteran healthcare writer, Chief Executive Officer
      Ken Buser deserves much of the credit for improving the visibility and reputation
      of All Saints Healthcare, Racine, Wis.

PMID- 12055971
TI  - What's as exciting as a new baby? Answer: a brand-new hospital, just for women.
AB  - An exciting campaign including advertising teasers and "birth announcements"
      heralds the opening of The Women's Hospital, Newburgh, Ind., part of Deaconess
      Health System.

PMID- 12055972
TI  - Allina Web site offers visitors a chance for conversation. One of the nation's
      'most wired,' it also is quite accessible.
AB  - Allina Hospitals & Clinics, Minneapolis, receives increased visitors after
      improving its Web site, Medformation.com. The system is one of those named by
      Hospitals & Health Networks as "one of the 100 Most Wired Hospitals."

PMID- 12055973
TI  - Phoenix Children's Hospital expands to meet rapid growth. This Cinderella story
      has a happy ending.
AB  - The need for a children's hospital has grown quickly, along with the rapid rate
      of growth of the city of Phoenix. When Phoenix Children's Hospital outgrew its
      existing space, it built a new facility--which is now one of the 10 largest
      children's hospitals in the U.S. A variety of media and events was used to invite
      community-wide participation in the development of the project, which opened
      officially in April.

PMID- 12055974
TI  - Norton Healthcare's campaign strategy: focus on employees. They appear in
      commercials and attend preview showings.
AB  - Norton Healthcare, a 2,000-bed system with headquarters in Louisville, Ky.,
      previewed its big branding campaign with its 8,000 employees. During National
      Hospital Week, employees viewed a five-minute behind-the-scenes video showing
      more than 50 of their colleagues serving as actors and models in the TV, radio
      and print ads.

PMID- 12055975
TI  - Home care facing critical issues. Home Care Human Resources Sector Study: phase I
      results.

PMID- 12055976
TI  - ARNET funding to RNs increases 540 per cent in 2001.

PMID- 12055977
TI  - Highlights from the states: Medicare--insuring health care for the elderly. Part
      I: Medicare as the payer.

PMID- 12055978
TI  - Of specialty interest: publications of the National Institute on Deafness and
      Other Communication Disorders.

PMID- 12055979
TI  - Patient education: tips for avoiding injury during your balance disturbance.

PMID- 12055980
TI  - Geriatric otorhinolaryngology: embracing the challenge.

PMID- 12055981
TI  - Presidential perspectives: SOHN--state of the organization.
AB  - In 2001, the Society of Otorhinolaryngology and Head-Heck Nurses (SOHN)
      celebrated 25 years of success and the end of a quarter century of excellence in
      ORL nursing. As we begin the next quarter century, the organization faces new
      challenges, not only in nursing, but throughout the world. We are more than ready
      to face those challenges. The officers and Board of Directors have re-examined
      SOHN's current strategic plan and SOHN committees are working on projects aimed
      at completing each strategic priority.

PMID- 12055982
TI  - The hypothalamic-pituitary-adrenal axis in the pathogenesis of rheumatic
      diseases.
AB  - Many studies have demonstrated altered HPA axis activity in patients with
      rheumatic diseases. In the case of autoimmune inflammatory diseases,
      circumstantial evidence suggests that failure of the neuroendocrine-immune
      regulatory loop may lead to insufficient production of endogenous glucocorticoid.
      Nevertheless, in human autoimmune disease, it is not possible to determine if
      altered HPA axis activity predates the onset of chronic inflammation. Animal
      studies and some early genetic studies in RA patients lend credibility to the
      argument that insufficient HPA axis response to inflammatory stimuli may increase
      susceptibility to, or severity of, these diseases. Most patients with rheumatic
      diseases complain of musculoskeletal pain. There is evidence of HPA axis
      involvement in acute and chronic pain. In the case of FM, pain cannot be
      explained on the basis of inflammation or altered musculoskeletal anatomy. This
      has led to the hypothesis that central nervous system mechanisms contribute to
      the symptom of somatic pain. Again, it is unclear if the observed HPA axis
      abnormalities reflect pre-existing vulnerability to the FM spectrum of disease,
      or whether chronic somatic symptoms alter HPA axis activity. Availability of
      technology to study better central components of the HPA axis may shed further
      light on its role in the pathogenesis of inflammatory autoimmune rheumatic
      diseases and musculoskeletal pain syndromes.

PMID- 12055983
TI  - Endocrine abnormalities in chronic renal failure.
AB  - Much needs to be achieved in improving survival and quality of life for chronic
      renal failure patients. Progress in attaining this goal may accrue from attention
      to underlying pathophysiologic processes early and throughout a person's life.
      The endocrine perturbations described in this article--alterations in the
      homeostasis of phosphorus, calcium, vitamin D and parathyroid hormone;
      erythropoietin deficiency; and sexual dysfunction in uremia--provide good
      examples for the need to identify early and manage prospectively over time
      manifestations of chronic renal failure. The complexity of the skeletal and
      extraskeletal sequelae of dysregulated mineral metabolism and the complications
      of chronic anemia have been discussed, while stressing possible implications of
      these endocrine abnormalities for both morbidity and mortality. There is a great
      need for more randomized clinical trials to evaluate new and old treatment
      approaches, with the goal of developing better evidence-based practice
      guidelines.

PMID- 12055984
TI  - Systemic diseases associated with disorders of water homeostasis.
AB  - Disorders of AVP secretion and action sometimes present as the first
      manifestation of a variety of different systemic diseases. It is prudent for the
      clinician to consider these causes in the differential diagnosis of hypoosmolar
      hyponatremia, polyuria and polydipsia, since recognizing the underlying disorder
      may affect treatment decisions, and intervention directed at the primary disorder
      often can reverse the abnormal water metabolism in these patients. Although much
      of the pathophysiology of these disorders is not understood completely, great
      progress has been made toward appreciating the complex and precise system
      involving thirst, AVP secretion, and renal responsiveness to AVP. Further
      investigation in this field likely will allow physicians to offer more effective
      and potent treatments in the future, such as the development of AVP V2 receptor
      antagonists for the treatment of SIADH [81] and edema-forming states [18, 109].

PMID- 12055986
TI  - Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: multiple
      interactions and disturbances in sleep disorders.
AB  - Sleep is an important component of mammalian homeostasis, vital for survival.
      Sleep disorders are common in the general population and are associated with
      significant medical, psychologic, and social disturbances. Sleep, in particular
      deep sleep, has an inhibitory influence on the HPA axis, whereas activation of
      the HPA axis or administration of glucocorticoids can lead to arousal and
      sleeplessness. Insomnia, the most common sleep disorder, is associated with a 24
      hour increase of ACTH and cortisol secretion, consistent with a disorder of
      central nervous system hyperarousal. Sleepiness and fatigue are very prevalent in
      the general population, and recent studies have demonstrated that the
      proinflammatory cytokines IL-6 and/or TNF-alpha are elevated in disorders
      associated with excessive daytime sleepiness, such as sleep apnea, narcolepsy,
      and idiopathic hypersomnia. Sleep deprivation leads to sleepiness and daytime
      hypersecretion of IL-6. Combined, these findings suggest that the HPA axis
      stimulates arousal, while IL-6 and TNF-alpha are possible mediators of excessive
      daytime sleepiness in humans.

PMID- 12055985
TI  - Hypercalcemia in malignant and inflammatory diseases.
AB  - Hypercalcemia is one of the most common metabolic abnormalities in human disease.
      Although there are many causes, most cases are due to neoplasia. Understanding
      the pathophysiology can lead to correct diagnosis and effective therapy for most
      patients.

PMID- 12055987
TI  - Nonthyroidal illness syndrome: evaluation of thyroid function in sick patients.
AB  - Altered thyroid function tests as a consequence of illness have been recognized
      for many years, yet the cause and clinical implications remains uncertain. The
      routine testing of thyroid function in hospitalized patients should be
      discouraged, as the results are less predictive of primary thyroid disease than
      in ambulatory patients. Clinicians should be aware of the methods used for
      thyroid function testing, as the effect of illness on thyroid function varies
      among the different tests. The most commonly used free T4 assays likely are
      influenced significantly by nonthyroidal illness. Advances in understanding the
      basic mechanisms of thyroid hormone metabolism and thyroid hormone action have
      given insights into the changes in thyroid function tests as a consequence of
      nonthyroidal illness. In the future, thyroid hormone receptor isoform-specific
      agonists and antagonists may allow for more specific treatment of select patients
      with nonthyroidal illness syndrome.

PMID- 12055988
TI  - Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol
      secretion.
AB  - Obesity and starvation have opposing affects on normal physiology and are
      associated with adaptive changes in hormone secretion. The effects of obesity and
      starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table
      1. Although hypothyroidism is associated with some weight gain, surveys of obese
      individuals show that less than 10% are hypothyroid. Discrepancies have been
      reported in some studies, but in untreated obesity, total and free T4, total and
      free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest
      an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of
      obesity with hypocaloric diets causes changes in thyroid function that resemble
      sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and
      free T3 with a corresponding increase in rT3. untreated obesity is also
      associated with low GH levels; however, levels of IGF-1 are normal. GH-binding
      protein levels are increased and the GH response to GHRH is decreased. These
      changes are reversed by drastic weight reduction. Cortisol levels are abnormal in
      people with abdominal obesity who exhibit an increase in urinary free cortisol
      but exhibit normal or decreased serum cortisol and normal ACTH levels. These
      changes are explained by an increase in cortisol clearance. There is also an
      increased response to CRH. Treatment of obesity with very low calorie diets
      causes a decrease in serum cortisol explained by a decrease in cortisol-binding
      proteins. The increase in cortisol secretion seen in patients with abdominal
      obesity may contribute to the metabolic syndrome (insulin resistance, glucose
      intolerance, dyslipidemia, and hypertension). States of chronic starvation such
      as seen in anorexia nervosa are also associated with changes in thyroid hormone,
      GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and
      an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH
      response to TRH is diminished and, in severe cases, thyroid-binding protein
      levels are decreased. In regards to GH, there is an increase in GH secretion with
      a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see
      text] changes in cortisol secretion in patients with anorexia nervosa resemble
      depression. They present with increased urinary free cortisol and serum cortisol
      levels but without changes in ACTH levels. In contrast to the findings observed
      in obesity, the ACTH response to CRH is suppressed, suggesting an increased
      secretion of CRH. The endocrine changes observed in obesity and starvation may
      complicate the diagnosis of primary endocrine diseases. The increase in cortisol
      secretion in obesity needs to be distinguished from Cushing's syndrome, the
      decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished
      from secondary hypothyroidism, and the increase in cortisol secretion observed in
      anorexia nervosa requires a differential diagnosis with primary depressive
      disorder.

PMID- 12055989
TI  - Ectopic pro-opiomelanocortin syndrome.
AB  - Ectopic POMC syndrome remains one of the most challenging differential diagnoses
      in endocrinology. Recent progress in the understanding of the tissue specific
      regulation of POMC gene expression and new insights into the processing of the
      POMC peptide in nonpituitary tissues has helped elucidate some of the molecular
      events leading to ectopic expression and secretion of POMC peptides.
      Corticotropin and other POMC-derived peptides have diverse effects on adrenal
      steroidogenesis, growth, and extra-adrenal tissues. Differences in POMC gene
      regulation in the corticotrope versus ectopic POMC-producing tumors provides a
      scientific framework for the clinical distinction between eutopic and ectopic
      Cushing's syndrome. In an attempt to revisit recent basic and clinical advances
      in the diagnosis of ectopic POMC syndrome the authors undertook an extensive
      literature review of 530 cases in 197 published papers and provided a molecular
      biologic, demographic and diagnostic update. According to this review, the four
      most common causes of ectopic POMC syndrome are the small cell carcinoma of the
      lung (27%), bronchial carcinoids (21%), islet cell tumor of the pancreas (16%),
      and thymic carcinoids (10%). Although the clinical features of patients with
      ectopic POMC syndrome are similar to those with Cushing's disease, subgroup
      analysis reveals a broad spectrum of severity and progression of signs and
      symptoms of hypercortisolism. The endocrine workup of a patient with suspected
      ectopic POMC syndrome includes the establishment of pathologic hypercortisolism,
      diagnosis of corticotropin dependency, and the differential diagnosis of
      corticotropin-dependent Cushing's syndrome. The use of a variety of baseline
      endocrine values, dynamic endocrine testing, and invasive procedures leads to the
      correct diagnosis in the majority of patients with ectopic POMC syndrome.
      Diagnostic imaging, including conventional radiological techniques and
      somatostatin receptor scintigraphy, aids in the correct localization and eventual
      treatment of ectopic POMC production.

PMID- 12055990
TI  - Divergent endocrine abnormalities in melancholic and atypical depression:
      clinical and pathophysiologic implications.
AB  - Mediators of neuroendocrine and autonomic function seem to play important roles
      in the core symptoms of major depression. Although centrally directed
      corticotropin-releasing hormones and norepinephrine contribute to core symptoms
      such as alterations in anxiety, arousal, and mood, they also exert significant
      potentially clinically relevant effects on key processes that proceed in the
      periphery. Thus, the core clinical manifestations of major depression may
      represent a fraction of a complicated systemic illness that not only influences
      thought and feeling, but also the processes involved in premature cardiovascular
      disease, osteoporosis, and premature death. Subdividing patients with major
      depression into meaningful biologic subgroups will facilitate the elucidation of
      the mechanisms that underlie the central and peripheral manifestations of major
      depressive illness.

PMID- 12055991
TI  - The hypothalamic-pituitary-gonadal axis in mood disorders.
AB  - This article has demonstrated that stress and HPA axis activation affect the
      reproductive axis. Despite similarities in the HPA axis picture between women
      with major depression and those with hypothalamic amenorrhea and exercise or
      nutritional amenorrhea, no abnormalities in LH secretion have been documented in
      major depression. Lower estradiol in the follicular phase in depressed women and
      lower testosterone in depressed men however, have been observed [81, 92].
      Although PMS would appear to be the best candidate for a mood disorder associated
      with abnormalities in reproductive hormones, no abnormalities in LH, estradiol or
      progesterone have been documented in PMS either [62]. Similarly, blockade of
      progesterone appears to be ineffective as a treatment for PMS [79]. Complete
      elimination of monthly cycling with leuprolide improves mood, however. No
      published studies have examined women with major depression to determine whether
      leuprolide will exacerbate or improve depressive symptoms. Some studies suggest
      beneficial effects of estrogen on mood in postmenopausal women, but no placebo
      controlled studies have explored estrogen augmentation in the treatment of major
      depression in either post- or premenopausal women, although estrogen is
      beneficial in women with perimenopause-related mood disorders [78].

PMID- 12055992
TI  - Role of epinephrine in acute stress.
AB  - This article presents the likely pathway of stimuli generated by the recognition
      of high-intensity stressors to ultimately produce a fight-or-flight response. A
      key element is the recognition that psychological stressors that do not directly
      alter the internal environment represent the most important etiology of a fight
      or-flight response. Adrenomedullary secretion is a critical component of that
      response; impromptu stimulation of the adrenal medulla can produce plasma
      epinephrine concentrations greater than 10,000 pg/mL. When these plasma levels
      reach the hypothalamus to act on the CNS, the result is facilitation of the
      decision making, and decision execution processes (fight-or-flight), and perhaps
      further sympathetic stimulation and vasopressin release. Subjects with underlying
      cardiovascular and/or metabolic pathology may be particularly susceptible to
      potentially lethal reactions to this neuroendocrine response. Additionally, since
      this biological reaction may be triggered by sudden changes in the social
      environment, the coordinated actions of epinephrine, sympathetic stimulation and
      vasopressin must be directed at not only optimizing the chances for survival, but
      also at attaining maximal preservation of the individual environmental and social
      domains.

PMID- 12055993
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Hypothalamic hormones].

PMID- 12055994
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Therapy for patients with pituitary neoplasm].

PMID- 12055995
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicIne in the last 100 years: Thyroid autoantibodies].

PMID- 12055996
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Suppressive and stimulative tests for
      adrenocortical function].

PMID- 12055997
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Vitamin D metabolic systems].

PMID- 12055998
TI  - [Progress in studies of diabetes mellitus in the last 100 years in Japan].

PMID- 12055999
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Obesity and adipocytes].

PMID- 12056000
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Changes in methods of hormone analysis].

PMID- 12056001
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Diagnostic imaging of endocrine diseases].

PMID- 12056002
TI  - [Progress in studies of endocrinology and metabolism in the field of internal
      medicine in the last 100 years: Diagnosis and classification of diabetes
      mellitus].

PMID- 12056003
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years:
      Hashimoto's disease].

PMID- 12056004
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: Insulin
      autoimmune syndrome].

PMID- 12056005
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years:
      Development of statins].

PMID- 12056006
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years:
      Artificial endocrine pancreas].

PMID- 12056007
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years:
      Lymphocytic infundibuloneurophypophysitis as a cause of idiopathic diabetes
      insipidus].

PMID- 12056008
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: Tarui's
      disease(muscular phosphofructokinase deficiency)].

PMID- 12056009
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: Abnormal
      insulin].

PMID- 12056010
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: Slowly
      progressive insulin-dependent diabetes mellitus (SPIDDM)].

PMID- 12056011
TI  - [Contribution of Japanese researchers to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: ATP
      sensitive potassium channel and insulin secretion].

PMID- 12056012
TI  - [Contribution of Japanese researcher to the progress of studies in endocrinology
      and metabolism in the field of internal medicine in the last 100 years: Vitamin D
      dependent rickets].

PMID- 12056013
TI  - [History of research on diabetes insipidus].

PMID- 12056014
TI  - [History of research on pituitary neoplasm and hypopituitarism].

PMID- 12056015
TI  - [History of research on adrenal cortex function disorders].

PMID- 12056016
TI  - [History of research on multiple endocrine neoplasia, MEN].

PMID- 12056017
TI  - [History of research on thyroid function disorders].

PMID- 12056018
TI  - [History of research on parathyroid function disorders].

PMID- 12056019
TI  - [History of research on diabetes mellitus].

PMID- 12056020
TI  - [Recent studies on hyperlipidemia].

PMID- 12056021
TI  - [History of research on gonadal dysfunction].

PMID- 12056022
TI  - [Retrospective thoughts on endocrine and metabolism studies in the 20th century,
      and the prospects for the 21st century(discussion)].

PMID- 12056023
TI  - [Practice guidelines review: Diabetes mellitus].

PMID- 12056024
TI  - [Practice guidelines review: Hyperlipidemia].

PMID- 12056025
TI  - [Practice guidelines review: Pseudohypoparathyroidism].

PMID- 12056026
TI  - [Practice guidelines review: Adrenal gland dysfunction].

PMID- 12056027
TI  - [Practice guidelines review: Pituitary gland dysfunction].

PMID- 12056028
TI  - [Diabetes mellitus with mixed neuroendocrine-neural tumor].

PMID- 12056029
TI  - [Systemic lupus erythematosus complicated with antiphospholipid syndrome
      diagnosed from intrauterine growth retardation].

PMID- 12056030
TI  - [Two cases of nontuberculous mycobacterial lung infection associated with
      Welder's lung].

PMID- 12056031
TI  - [Recovered case of severe Japanese spotted fever].

PMID- 12056032
TI  - [Autopsy case of aortic intimal sarcomas with severe hypertension and congestive
      heart failure].

PMID- 12056033
TI  - [Migraine-related stroke with transient antiphospholipid antibody].

PMID- 12056034
TI  - [Evaluation of the management of blunt renal trauma and indication for surgery].
AB  - OBJECTIVES: Appropriate management of renal trauma is still controversial. Many
      of the patients have minor injuries and conservative treatment can achieve
      excellent outcomes without any complications. For major injuries of deep
      lacerations or ruptures, we have been performing early surgical treatment to
      salvage the kidney in the selected cases after the precise evaluation of the
      injury. To obtain the optimal management options, we evaluated the clinical
      results of our procedures. PATIENTS AND METHODS: We conducted a retrospective
      study, which included 106 cases of blunt renal trauma with evident etiology over
      the past 22 years and 9 months. The severity of the injury was evaluated mainly
      by CT scanning. The indication of renal exploration included persistent renal
      bleeding, large hematoma around the kidney, dislocated fragments, nonviable
      tissue, massive urinary extravasation and vascular injury. With the patients who
      required an operation, we first controlled the bleeding by clamping the hilar
      vessels. Then, the final decision whether to repair or remove the kidney was made
      based on the direct inspection of the injured kidney after the complete removal
      of the hematoma. The severity of renal trauma was classified by the
      classifications found in The Organ Injury Committee of the American Association
      for the Surgery of Trauma. RESULTS: Sixty-three patients were managed
      conservatively without any interventions, while 22 surgical repairs and 21
      nephrectomies were performed. Of the 63 patients, 35 patients (81.4%) were
      operated on within 2 days after the injury. Judging from systolic blood pressure,
      red cell count, blood loss during surgery and transfusion requirements,
      surgically treated patients were more severely injured than conservatively
      treated patients. And nephrectomized patients than surgically repaired patients.
      All the surgically repaired cases were confirmed to have preserved renal
      functions postoperatively. In all of the 50 patients with Grade I injuries,
      conservative treatment was successful. Eight out of the 19 Grade II and III
      cases, who were indicated for kidney exploration because of multiple lacerations
      or considerable bleeding, were also successfully repaired. Localized hematoma
      with no urine leakage, even when it was large, settled spontaneously without
      complication. For the 37 Grade IV and V injuries, including 4 cases with hilar
      injuries, we implemented conservative procedures on 2 patients, surgical repair
      on 14 patients and nephrectomy on 21 patients. In the conservatively treated
      cases, one deep laceration with relatively large, but localized, hematoma, and
      minimal urine extravasation healed spontaneously. Atrophy of the segment and
      hypertension developed in the other ruptured kidney with dislocated fragments,
      large hematoma and urine leakage. This kidney, which also required later surgical
      exploration, did have good parenchymal blood flow. Hilar injury cases were all
      resulted in nephrectomy. CONCLUSION: In most of our cases the indication for
      surgical exploration or nephrectomy based on our criteria seemed to be properly
      decided. Several cases, though, might have received overtreatment. Recent
      advances in evaluations and strategies of renal trauma have decreased the need
      for surgical exploration. This may have overreached the indication for
      conservative management. Severely injured kidneys may be managed conservatively
      because in most cases bleeding settles after the full formation of large hematoma
      within the Gerota's fascia. In such cases, though, no one can predict whether the
      injury will heal spontaneously or not, and, moreover, whether a complication will
      develop or not. We think that the optimal management of the patient requires an
      accurate evaluation of the injured kidney. Therefore the indication for surgical
      exploration should be made based on the degree of the injury.

PMID- 12056035
TI  - [Treatment of metastatic germ cell tumors with etoposide and cisplatin as first
      line chemotherapy].
AB  - PURPOSE: The efficacy and toxicity of two-drug therapy (etoposide and cisplatin,
      EP) in patients with metastatic germ cell tumors were investigated. PATIENTS AND
      METHODS: Between December 1996 and November 1999, 18 patients with metastatic
      germ cell tumors (6 seminomas and 12 non-seminomas, Stage II 8, Stage IIIA 2,
      Stage IIIB 6, Stage IIIC 2) were treated by 3-5 cycles of induction chemotherapy
      regimen (EP). Etoposide and cisplatin were administrated in doses of 100 mg/m2
      and 20 mg/m2, respectively, on days 1 to 5 and then repeated from day 21. After
      tumor markers obtained normal levels, one or two additional cycles of EP were
      continued. Patients showing evidence of residual tumor mass underwent debulking
      surgery as early as possible. RESULTS: At the end of EP therapy, 4 (22%) of the
      18 patients achieved complete remission and 14 patients (78%) showed partial
      remission. Seven patients of partial remission were treated by excision of
      residual abnormalities: 6 had pathologically necrotic debris in the resected
      specimen and 1 had teratoma, and these 7 patients all achieved complete
      remission. Four other patients achieving partial remission were followed without
      surgical excision and have had no evidence of disease progression. Remaining
      three patients achieving partial remission received salvage chemotherapy with or
      without adjunctive surgery, resulted in complete remission in 2 patients and
      partial remission in 1 patient. EP demonstrated to have less treatment-related
      toxicity compared with that of EBP. Follow up studies ranging from 12 to 47
      months (median, 29.6) showed that one patient experienced a relapse from complete
      remission at 13 months and was salvaged by chemotherapy and surgery. Finally,
      thirteen patients (72%) who achieved complete remission are alive and disease
      free and 5 patients (28%) showing partial remission are alive with negative tumor
      markers and no evidence of relapse. CONCLUSION: These results suggests that EP is
      an efficacious and less toxic first line regimen for good-prognosis patients with
      metastatic germ cell tumors.

PMID- 12056036
TI  - [The value of using urinary red cell volume distribution curve of patients with
      positive urinary occult blood detected in a mass examination].
AB  - PURPOSE: We investigated the usefulness of the urinary red blood cell volume
      distribution curve (RVDC) for screening patients who are positive for
      asymptomatic urinary occult blood on mass examination. SUBJECTS AND METHODS: The
      subjects were 200 individuals over 40 years old (44 men with a median age of 53.4
      years and 156 women with a median age of 57.2 years) who were positive for
      urinary occult blood on mass examination between January 1993 and December 1994.
      The subjects were classified into three groups based on the pattern of their
      RVDC. Group NG showed a nonglomerular pattern, group M showed a mixed pattern,
      and group G showed a glomerular pattern. The urological examinations performed
      included DIP, ultrasound of the kidney and urinary bladder and urethrocystoscopy.
      To investigate the prognosis, a questionnaire was sent to all subjects in
      September 1999 in which they were asked about the state of their disease during
      the period since the initial examination. RESULTS: Group G consisted of 192
      patients, or almost all of the subjects (96%). There were five patients (2.5%)
      who had serious urological diseases, including two with bladder cancer, and all
      were found in Groups NG and M. During the period from initial examination until
      the prognosis survey (mean of 5.7 year), one patient in group G developed both
      bladder and ureteral cancer. The CVDC showed a mixed pattern when this patient
      was discovered. CONCLUSION: RVDC was useful for screening patients who were found
      to be positive for urinary occult blood on mass examination. When the RVDC shows
      a non-glomerular or mixed pattern, detailed urological examination including
      endoscopy is necessary.

PMID- 12056037
TI  - [MHC-class I expression on prostate carcinoma and modulation by IFN-gamma].
AB  - OBJECTIVES: In this study, we investigated MHC-class I expression on both
      prostate cancer and normal prostate and compared those data with the number of
      CD8+ lymphocyte. Secondary, we investigated effect of IFN-gamma to the MHC-class
      I expression on prostate carcinoma. MATERIALS AND METHODS: Twenty cryo-preserved
      benign prostate samples (Seven normal prostates and five benign prostatic
      hypertrophy samples.) and fifteen prostate carcinoma samples were used for
      immunohistochemistry of CD8 and MHC-class I. Eleven fresh single cell suspensions
      of prostate carcinoma were used for IFN-gamma study. After 24 hours IFN-gamma
      stimulation, MHC-I expression was measured by FACs analysis. RESULTS:
      Interestingly, significant correlation was observed between MHC-class I
      expression and the CD8+ lymphocyte infiltrate (r = 0.705, P < 0.0001). After 24
      hrs IFN-gamma stimulation, MHC-class I expression was up-regulated in all samples
      (p < 0.05). CONCLUSION: Reduced expression of MHC-class I was thought as one of
      the factor which is related to the reduced degree of TILs (tumor infiltratig
      lymphocytes) in prostate cancer. IFN-gamma which is secreted mainly from CTL
      (cytotoxic T lymphocyte) might increase the degree of TIL through up-regulated
      MHC-class I.

PMID- 12056038
TI  - [A Japanese version of the National Institutes of Health Chronic Prostatitis
      Symptom Index (NIH-CPSI, Okayama version) and the clinical evaluation of cernitin
      pollen extract for chronic non-bacterial prostatitis].
AB  - PURPOSE: The chronic prostatitis syndromes are common disorders in urologic
      practice and present various clinical symptoms. The development of a chronic
      prostatitis symptom index appropriate for judgment of therapeutic effects is
      awaited since the pathophysiology and appropriate treatment are not well defined
      so far. We developed a Japanese version of the National Institutes of Health
      Chronic Prostatitis Symptoms Index (NIH-CPSI, Okayama version), and examined its
      usefulness. In addition, we evaluated clinical effects of Cernilton for chronic
      nonbacterial prostatitis using this symptom index. SUBJECTS AND METHODS: A total
      of 87 patients including 34 patients with NIH chronic prostatitis category III,
      35 patients with BPH and 18 patients for control group who visited the Department
      of Urology at Okayama University Medical School filled in the questionnaire of
      our Japanese version of the NIH-CPSI to compare the NIH-CPSI scores among three
      groups. Twenty-four patients with NIH chronic prostatitis category III (IIIa 16,
      IIIb 8) were treated with Cernilton and the NIH-CPSI scores were examined before
      and after its administration. RESULTS: The pain/discomfort domain score was 9.79
      (mean) in the chronic prostatitis group, 1.66 in the BPH group and 0.39 in the
      control group; that of the urinary symptom domain was 3.82, 3.29 and 0.72,
      respectively; and that of the quality of life (QOL) was 8.21, 4.17 and 1.39,
      respectively. The pain/discomfort domain score was significantly higher in the
      chronic prostatitis group than in the other groups; the QOL domain score was
      higher in the order of the chronic prostatitis group, the BPH group and the
      control group. In the chronic prostatitis group, there was a significant,
      positive correlation between the pain/discomfort domain score and that of the
      QOL, and between the urinary symptom domain score and that of the QOL. These
      results suggested the usefulness of our Japanese version of the NIH-CPSI as a
      parameter of the severity of chronic prostatitis. Examination of changes in the
      NIH-CPSI scores revealed that scores of the items in all domains were
      significantly lower 4 to 6 weeks after the start of administration of Cernilton
      than those obtained before the drug administration in patients with chronic
      prostatitis. CONCLUSIONS: A Japanese version of NIH-CPSI (Okayama version)
      accurately reflects clinical symptoms and the QOL in patients with chronic
      prostatitis. It seemed to be a useful and appropriate system for scoring symptoms
      of chronic prostatitis, indicating further studies on translation, adaptation and
      validation of the NIH-CPSI in Japan.

PMID- 12056039
TI  - [Prognostic value of serum immunosuppressive acidic protein in renal cell
      carcinoma].
AB  - BACKGROUND: To determine whether the immunosuppressive acidic protein (IAP) could
      be a useful marker for renal cell carcinoma (RCC), serum IAP levels were compared
      with clinicopathological features in RCC patients. Furthermore, IAP cutoff level
      to predict the recurrence was determined using receiver operating characteristics
      (ROC) curve analysis. PATIENTS AND METHODS: Between January 1994 and December
      1998, pretreatment serum IAP was measured in 123 consecutive patients with PCC at
      Kitasato University Hospital. Ninety-eight patients were received radical surgery
      and 86 patients were performed as clinically curable renal cell carcinoma (pT1
      pT3N0M0). ROC curve analysis was utilized to set the cutoff value of IAP for
      prediction of cancer recurrence. Significance of prognostic factors in RCC
      recurrence was analyzed by Cox proportional hazard model. RESULTS: The mean age
      of the 123 patients was 58.6 years (range 33 to 90, median 59). The mean follow
      up period was 24.8 months (range 1 to 78, median 26). The median IAP levels were
      447 ug/ml in stage I, 629 ug/ml in stage II, 588 ug/ml in stage III and 1,150
      ug/ml in stage IV (p < 0.05). Tumor size and venous involvement were
      significantly associated with IAP concentrations (p < 0.05). However, tumor grade
      did not correlate with IAP level. Of 86 patients with clinically curable tumor,
      79 patients were disease-free after median follow-up of 27 months. Using ROC
      curve analysis, IAP cutoff level for prediction of cancer recurrence was set at
      620 ug/ml. Disease-free survival rate in patients with preoperative IAP levels of
      620 ug/ml or lower was 98.5% (67/68) at 27 months postoperatively, whereas that
      in patients with IAP greater than 620 ug/ml was 75.0% (12/18). This difference
      was statistically significant (p < 0.05). Results of multivariate analysis
      revealed that preoperative IAP and pT stage were statistically significant
      factors for tumor recurrence after radical surgery (p < 0.05). CONCLUSIONS: The
      present study indicates that preoperative IAP level is a useful prognostic marker
      in patients with RCC. In particular, patients with clinically curable tumors (pT1
      3N0M0), whose preoperative IAP levels greater then 620 ug/ml may have high risk
      for recurrence after radical nephrectomy.

PMID- 12056040
TI  - [Surgical outcomes of nephron-sparing surgery for renal tumors].
AB  - PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing
      surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to
      March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors.
      The patients were divided into three groups. Group I comprised of 22 patients who
      underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were
      found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau
      disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The
      mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years
      and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18
      patients in Group I, and the remaining 4 patients were treated with 3
      simultaneous operations for bilateral renal tumors with or without 2 ex vivo
      surgeries. Group II consisted of 49 patients who had small RCCs with the normal
      contralateral kidney and underwent NSSs (elective indication). The mean age and
      tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III
      consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors,
      2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were
      treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/-
      29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2
      patients who had had multiple lung metastases preoperatively. The five-year tumor
      specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36
      months. In Group II, there were few peri-operative complications or no local
      recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis,
      which was removed surgically with no evidence of recurrence at 159 months after
      NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal
      function of the operated kidney. Improvement in surgical techniques resulted in
      less-invasive surgery in 22 operations during the last 4 years. The patients of
      Group III were also operated uneventfully, although 1 experienced postoperative
      bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III)
      serum creatinine level increased transiently, decreased to 1.3 times of
      preoperative values within 3 months, and almost recovered at 1-year follow-up.
      CONCLUSION: Excellent outcomes in cancer control and preservation of renal
      function support the validity of nephron-sparing surgery to treat renal tumors.
      The candidate patients may include those with bilateral kidney tumors, tumor
      occuring in the solitary kidney or small renal cell carcinomas with the normal
      contralateral kidney. Earlier detection of small lesions and less invasive
      surgical techniques will facilitate a wider indication of NSS.

PMID- 12056041
TI  - [Evaluation of transrectal power-Doppler ultrasonography and effect of contrast
      enhancement for detecting prostate cancer].
AB  - PURPOSE: There are many reports about the usefulness of transrectal power-Doppler
      ultrasonography (PDUS) for detecting prostate cancer because of the high
      microvessel density in cancerous tissue in the prostate. The purpose of this
      study was to assess the role of PDUS and contrast-enhanced transrectal power
      Doppler ultrasonography (enhanced PDUS) in the identification of prostate cancer.
      MATERIALS AND METHODS: One hundred forty-two cases (90 cases without enhancement,
      52 cases with enhancement) of suspected prostate cancer found with digital rectal
      examination (DRE), transrectal ultrasound (TRUS) abnormal or prostate specific
      antigen (PSA) elevation were evaluated by PDUS and enhanced PDUS. RESULTS: Forty
      three (30.3%) cases of cancer were detected, and there was a significant
      difference (p < 0.05) between PDUS group (22 cases, 24.4%) and enhanced PDUS (21
      cases, 40.0%). However, there were no significant statistical results about the
      usefulness of enhancement to detect prostate cancer although imaging was clear
      with contrast agent. The results of statistical analysis of PDUS use were almost
      the same as for PSA of more than 10.1 ng/ml. Combination with PDUS was very
      helpful to detect prostate cancers. The positive predictive value of the
      combination with DRE, TRUS and PSA improved from 68.0% to 81.0% with the addition
      of PDUS. In particular, cancer was revealed frequently (65.8%) in peripheral
      hypoechoic lesions on gray-scale TRUS with hypervascular areas on PDUS.
      CONCLUSIONS: We conclude that enhancement with contrast agent is not especially
      useful in the identification of prostate cancer although imaging was clear with
      contrast agent. However, PDUS is useful especially for hypoechoic peripheral
      areas. It is suggested that we should add PDUS to DRE, TRUS and PSA examinations.

PMID- 12056042
TI  - [A report of two cases of priapism with metastatic penile tumor].
AB  - We report two cases of priapism with metastases to the penis. The first case was
      a 52-year old man, diagnosed as suffering from gastric cancer by endoscopic
      biopsy five years previously, but for whom no treatment was performed. He visited
      our office due to priapism with a duration of 11 days. Physical examination
      showed two palpable mass lesions on the glans. A glansocavernosum shunt (Winter
      shunt) was performed, but this was not effective. Radiotherapy was also
      ineffective. Pathological analysis revealed gastric cancer metastasis to the
      penis and this was diagnosed as the cause of the priapism. He died of respiratory
      failure on postoperation day 28. The second case was a 64-year old man with
      kidney cancer. Hemodialysis had been performed due to chronic renal failure for
      20 years and visited our office due to priapism from which he had suffered for 30
      days. Computed tomography (CT) demonstrated a left renal cell cancer and
      metastasized to the retroperitoneal lymph nodes. A Winter shunt was performed on
      the penis and then a cavernosospongiosum anastomosis was done. The priapism
      improved about 40%. Pathological analysis confirmed that the renal cell cancer
      had metastasized to the penis and this was concluded to be responsible for the
      priapism.

PMID- 12056043
TI  - [A case of stone formation in the Mainz pouch using appendix as the efferent
      limb: a case report].
AB  - A large calculus (6.0 x 4.5 x 7.0 cm sized) in the continent urinary pouch was
      detected incidentally by computed tomography in a 7-year-old man with a gall
      bladder stone. He underwent a total cystectomy and Mainz pouch formation using
      appendix as the efferent limb for bladder cancer 7 years ago. Urine culture
      showed Proteus mirabilis and Escherichia coli, and urine pH was 8.5. The stone
      was removed successfully through a pouchotomy and composed mainly of struvite.
      The stone analysis was MAP; 88% and CaCO3; 12%. Convalescence was uneventful.
      This is the first case of in Mainz pouch using appendix as the efferent limb.

PMID- 12056044
TI  - [A case of orchitis following vaccination with freeze-dried live attenuated mumps
      vaccine].
AB  - In Japan, freeze-dried live attenuated mumps vaccine has been used optionally
      since 1981. The effectiveness of mumps vaccination has been established by
      worldwide research since 1971. On the other hand, because of it's live activity
      several untoward effects have been reported. Vaccination-related mumps orchitis
      is a rare adverse effect of mumps vaccine. Only 9 cases of vaccination-related
      mumps orchitis have been reported in Japan. We describe a case of orchitis
      following mumps vaccination in adolescence. A 16 years-old male has admitted
      because of acute orchitis with high fever and painful swelling of right testis.
      The patient had received vaccination with freeze-dried live attenuated mumps
      vaccine 16 days before admission. After admission, the bed-rest had completely
      relieved the symptoms on 6th hospital day. The impaired testis has maintained
      normal size and consistency 6 months after discharge.

PMID- 12056045
TI  - [Tuberculous epididymitis following intravesical Bacillus Calmette-Guerin
      therapy].
AB  - Bacillus Calmette-Guerin (BCG) immunotherapy is increasingly being accepted for
      management of some bladder transitional cell neoplastic lesions. Mild adverse
      reactions occur frequently. However, an unusual complication of tuberculous
      epididymitis is reported. A 64-year old man presented with bilateral epididymal
      mass. Four months earlier he had seven treatments with intravesical BCG
      instillation (Tokyo 172 strain) for a grade 2 transitional cell carcinoma in
      situ. Bilateral epididymectomy was performed. Microscopic examination of the
      epididymis revealed chronic inflammation and necrosis with granulomas and
      Langhans' giant cells. After the operation, there were no further complications.

PMID- 12056046
TI  - [Retroperitoneal bronchogenic cyst: a case report].
AB  - A rare case of retroperitoneal bronchogenic cyst is presented. A 50-year-old man
      was referred to our hospital for an investigation of a retroperitoneal mass.
      Computed tomography and magnetic resonance imaging confirmed a retroperitoneal
      mass, about 4 cm in diameter, adjacent to the left kidney and spleen. On the
      basis of these imaging modalities, a definitive diagnosis of this mass could not
      be made. So, resection of the mass was performed. The removed mass was an
      unilocular cyst and filled with mucinous fluid. Histopathologically, the cyst
      wall was composed of a fibrovascular connective tissue containing mucus-secreting
      glands and cartilages and was lined by ciliated pseudostratified columnar
      epitherium. Thus, a diagnosis of bronchogenic cyst was made. Bronchogenic cysts
      are rare congenital anomalies of the primitive foregut and usually develop in the
      mediastinum and lung.

PMID- 12056047
TI  - [Bilateral hydronephrosis associated with Buerger's disease: a case report].
AB  - A 28-year-old man visited our hospital complaining of the ulcerous lower
      extremity. An angiography showed the stenosis of the dorsal digital artery. The
      clinical diagnosis was Buerger's disease. The administration of prostaglandin I2
      (PG I2) and antithrombotic drug were done. The ulcerous lower extremity improved.
      But a computerized tomographic scan of the abdomen showed the bilateral
      hydronephrosis incidentally. A retrograde pyelography (RP) revealed the bilateral
      ureteral strictures. We suspected the etiology was the retroperitoneal fibrosis
      associated with Buerger's disease.

PMID- 12056048
TI  - [Science in atherosclerosis].
AB  - Ischemic heart disease and cerebral vascular accident are major cause of death in
      Japan. Development of these diseases is based on atherosclerosis, which would
      become evident in the middle-aged. Atherosclerosis is a process of aging, because
      its progression is closely associated with increase in age. Other factors such as
      smoking, eating habits and obesity are known to facilitate it. Therefore, it is
      very important for each one of us to learn the risk factors of atherosclerosis
      and to prevent it by paying attention to our life style. In this citizen joint
      symposium, we focused on the strategy for treatment and prevention of
      atherosclerosis by summarizing its mechanisms and consequences. Participation in
      the symposium could hopefully stimulate our civil activities against
      atherosclerosis and help promoting our health care in Hokkaido.

PMID- 12056049
TI  - Adenovirus-mediated overexpression of a cyclin-dependent kinase inhibitor,
      p57Kip2, suppressed vascular smooth muscle cell proliferation.
AB  - Vascular smooth muscle cell (VSMC) proliferation after arterial injury is playing
      a pivotal role in the pathogenesis of a number of vascular proliferative
      disorders including atherosclerosis and restenosis after balloon-mediated
      angioplasty. Thus, a better understanding of the molecular mechanisms underlying
      VSMC proliferation in response to injury would have important therapeutic
      implications. Cell proliferation is controlled by an intricate network of
      extracellular and intracellular signaling pathways which are processing various
      growth regulatory signals and integrating them into the basic cell-cycle
      regulatory machinery through control of cyclin dependent kinases (CDK). CDK are
      positively regulated by cyclins and negatively regulated by CDK inhibitory
      proteins (CKI). To dissect the role of CKI in VSMC proliferation, we prepared the
      replication-deficient adenovirus constructs expressing p21 family members (Ad
      CKI), p21Waf1, p27Kip1 and p57Kip2, respectively, and investigated the effect of
      CKI overexpression on the proliferation of vascular smooth muscle cells. The
      overexpression of each CKI protein in cultured VSMC was confirmed by western blot
      analysis. Flowcytometric analysis revealed that the Ad-CKI infected VSMC were
      largely retained in G1 phase, and had significantly less G2/M fraction than
      control cells. The extent of DNA synthesis in VSMC was assessed by [3H]-thymidine
      uptake, and shown to be inhibited by Ad-CKI dose dependently. Among three CKIs
      tested in this study, p57Kip2 showed the most significant suppression of DNA
      synthesis. In order to investigate in vivo effect of p57Kip2 overexpression, Ad
      p57 was locally delivered to the luminal wall of rabbit carotid arteries after
      balloon angioplasty. Histological examinations revealed that the local infection
      of Ad-p57 significantly suppressed the neointimal formation at the site of
      vascular injury. These results clearly demonstrated the antiproliferative role of
      p57Kip2 in VSMC, and also proposed a possibility of gene therapy approach for
      vascular proliferative disorders.

PMID- 12056050
TI  - [Ganglioside GM3-mediated modulation of insulin resistance in 3T3-L1 adipocytes].

PMID- 12056051
TI  - [Overexpression of PDZ domain-containing protein AIE-75 induces G2/M cell cycle
      arrest in human colorectal adenocarcinoma SW480 cells].

PMID- 12056052
TI  - [Roles of integrin beta 3 in enhancement of cell motility by HOXD3
      overexpression].

PMID- 12056053
TI  - [The role of macrophage migration inhibitory factor (MIF) in the process of
      peripheral nerve regeneration].

PMID- 12056054
TI  - [Investigation of patients' loyalties for primary care setting: a qualitative
      research of expectation of elderly people].

PMID- 12056055
TI  - [The effect of lipopolysaccharide on human cervical smooth muscle cells].

PMID- 12056057
TI  - [Subcutaneous nodules and lung cavitated nodules].
AB  - An african 22-year old man consulted because of disseminated subcutaneous nodules
      which appeared two months ago with an increasing number. He also complained from
      productive cough, wheezing and dyspnea on exertion. A chest CT-scan revealed
      multiple cavitated nodular lesions in both lungs.

PMID- 12056058
TI  - [New York -- Washington, September 11, 2001: the loss of illusions].

PMID- 12056060
TI  - [Recommendations for the management of acute chest pain. Report of the Belgian
      Interdisciplinary Group on Acute Cardiology].
AB  - The Belgium Interdisciplinary Working Group on Acute Cardiology (BIWAC),
      including cardiologists, intensivists and urgentists was formed to give consensus
      regarding the management of acute chest pain in the prehospital and the early
      hospital phases. General recommendations and critical pathways are proposed to
      improve the treatment of the patients with acute coronary syndromes.

PMID- 12056061
TI  - [Resistant arterial hypertension].
AB  - Many patients are considered to have resistant hypertension when their blood
      pressure remains elevated despite the use of multiple antihypertensive agents.
      Several factors can interfere with optimal control of blood pressure, some being
      patient-related, such as poor compliance, other being physician-related, such as
      the reluctance to increase treatment. These factors are often identified using a
      systematic approach, so that truly resistant hypertension is, in fact, uncommon.

PMID- 12056062
TI  - [Acute portal thrombosis revealing hereditary hemochromatosis: report of a case].
AB  - The authors report the case of a 49-year old man in whom an inaugural portal vein
      thrombosis led to the diagnosis of hereditary hemochromatosis. In this case, the
      increase in ferritinemia and the T2-weighted MRI hepatic segmental hyposignal
      were considered as consequences of tissular necrosis while they did probe a real
      iron overload. Genetic testing, revealing C282Y/H63D compound heterozygoty,
      provided evidence for a diagnosis of hereditary hemochromatosis. Weekly
      venesections induced a calculated iron depletion of 3.5 g without occurrence of
      anemia, further supporting the diagnosis. We suggest that hemochromatosis should
      be considered in the differential diagnosis of idiopathic portal vein thrombosis
      when signs of abnormal iron accumulation exist.

PMID- 12056063
TI  - [Increasing incidence of knee ligament injuries in alpine skiing: epidemiology
      and etiopathogenetic hypotheses].
AB  - 20 to 25% of all the injuries are due to traumas of the knee since forty years.
      The amount of serious sprains has been in constant increasing during the last
      four decades. The ratio of one to two in 1960 between and ankle injuries was of
      six to one in 1987. The inversion of this ratio is probably due to the evolution
      of technics from 1960 forth, to plastic shoes with thicker soles, to the wrong
      adjustment of binding and to the higher speed of the skiers thanks to better
      mending of tracks. The frequency of injury of ligamental structures is higher for
      the internal lateral ligament and for the anterior cruciate ligament. A valgus
      associated to internal leg rotation in consequence of blocking of internal edge
      and of forward falling causes internal lateral ligament injury. The three
      lesional mechanisms of the anterior cruciate ligament are the valgus connected
      with external rotation, the anterior draw caused by the shoe in case of backward
      falling and the association valgus-flexion-internal rotation ("foot-phantom").
      These lesions of ligaments are often connected with lesions of the external
      meniscus and with osseous contusions concerning the external femoral condyle and
      the external tibial plate.

PMID- 12056064
TI  - [Evaluation of diagnostic tests performance: the ROC curve].
AB  - Most of the diagnostic tests applied in clinic measure continuous or discrete
      ordinal variables and do not provide an "yes or no" response. Therefore, we can
      not assess tests nor compare them on the basis of a single pair of values of
      sensitivity and specificity. The ROC curve plots values of sensitivity against 1
      specificity and allows evaluation of the discriminatory power of a test for all
      ranges of sensitivity and specificity when applied in two populations, one
      presenting the target disease and the other not. Evaluation of the discriminatory
      power or comparison of different tests are further deducted from the measure of
      the area under the curve. The discriminatory power of the test demonstrated, one
      has to determine the cutoff point on the ROC curve, that will provide the best
      information for clinical application.

PMID- 12056065
TI  - [The choice and administration of corticoids in COPD].
AB  - Although the role of steroid inhalations is well established for the chronic
      treatment of asthmatic patients, their use in the chronic treatment of patients
      with COPD remains controversial. Steroid inhalations do not prevent the yearly
      FEV1 decline, which is an important prognostic factor of the disease. Inhaled
      steroid are not indicated for the treatment of early disease. For the patient
      with advanced disease (FEV1 < 50% of the predicted value) and presenting several
      exacerbations each year, inhaled steroids reduce the number of exacerbations and
      slow the progressive decline of quality of life. There is no place for continued
      oral glucocorticoid treatment. For mixed conditions (COPD and asthma), inhaled
      steroid may be of value.

PMID- 12056066
TI  - [Evolution of the Faculty Council].

PMID- 12056067
TI  - [Has MONICA honored its promises?].

PMID- 12056068
TI  - [Imaging of the month: postoperative pneumopericardium].

PMID- 12056069
TI  - [The J.E.P. 2001: comments on the cardiology "practice workshops"].

PMID- 12056070
TI  - [Risk factors for (pre)diabetes in children whose mothers or fathers are
      diabetic].

PMID- 12056071
TI  - [Hypoglycemia in the newborn].

PMID- 12056072
TI  - [The Third Annual Day of Thoracic Oncology of the Jules Bordet Institute, U.L.B].

PMID- 12056073
TI  - [Pierre Dustin, "A man in the Renaissance tradition"].

PMID- 12056074
TI  - Development and validation of a modified version of the Peritraumatic
      Dissociative Experiences Questionnaire.
AB  - This article reports results from 3 studies conducted to develop and validate a
      modified version of the self-administered form of the Peritraumatic Dissociative
      Experiences Questionnaire (PDEQ; C. R. Marmar, D. S. Weiss, & T. J. Metzler,
      1997). The objective was to develop an instrument suitable for use with persons
      from diverse ethnic and socioeconomic backgrounds. In Study 1, the original PDEQ
      was administered to a small sample (N = 15) recruited from among men admitted to
      the hospital for physical injuries stemming from exposure to community violence.
      Results led to modifications aimed at improving the utility of the instrument. In
      Study 2, the modified PDEQ was subjected to structural equation modeling and item
      response theory analyses to assess its psychometric properties in a larger,
      primarily male, sample of community violence survivors (N = 284). In Study 3, the
      reliability and validity of the modified instrument were further assessed in a
      sample of female survivors of sexual assault (N = 90). Results attest to the
      psychometric properties as well as the reliability and validity of the modified 8
      item PDEQ.

PMID- 12056075
TI  - The latent structure of analogue depression: should the Beck Depression Inventory
      be used to classify groups?
AB  - Research on depression is often conducted with analogue samples that have been
      divided into depressed and nondepressed groups using a cutoff score on the Beck
      Depression Inventory (BDI). Although the relative merits of different cut scores
      are frequently debated, no study has yet determined whether the use of any cut
      score is valid, that is, whether the latent structure of BDI depression is
      categorical or dimensional in analogue samples. The BDI responses of 2,260
      college students were submitted to 3 taxometric procedures whose results were
      compared with those of simulated data sets with equivalent parameters. Analyses
      provided converging evidence for the dimensionality of analogue depression,
      arguing against the use of the BDI to classify analogue participants into groups.
      Analyses also illustrated the notable impact of pronounced skew on taxometric
      results and the value of using simulated comparison data as an interpretive aid.

PMID- 12056076
TI  - The Children's Depression Inventory: error in cutoff scores for screening
      purposes.
AB  - The Children's Depression Inventory (CDI) is used to screen for depression in
      school-age children. Such screening uses the manual's reported information on
      suggested cutoff scores. These cutoff scores are based on an erroneous base-rate
      calculation and an inadequate methodology. Data are provided showing that for the
      suggested cutoff scores of 13 or 20, the CDI has poor receiver-operating
      characteristics. Indeed, for the cutoff score of 20, suggested as being suitable
      for screening in the general population (e.g., schools), clinicians will miss 86%
      of depressed children. In conclusion, it is recommended that the CDI is better
      suited as a continuous measure of mood and that cutoff scores should not be used
      to screen for the likely presence or absence of depression.

PMID- 12056077
TI  - Development and validation of a brief form of the Multidimensional Personality
      Questionnaire.
AB  - The Multidimensional Personality Questionnaire (MPQ; A. Tellegen, 1982, in press)
      provides for a comprehensive analysis of personality at both the lower order
      trait and broader structural levels. Its higher order dimensions of Positive
      Emotionality, Negative Emotionality, and Constraint embody affect and temperament
      constructs, which have been conceptualized in psychobiological terms. The MPQ
      thus holds considerable potential as a structural framework for investigating
      personality across varying levels of analysis, and this potential would be
      enhanced by the availability of an abbreviated version. This article describes
      efforts to develop and validate a brief (155-item) form, the MPQ-BF. Success was
      evidenced by uniformly high correlations between the brief- and full-form trait
      scales and consistency of higher order structures. The MPQ-BF is recommended as a
      tool for investigating the genetic, neurobiological, and psychological substrates
      of personality.

PMID- 12056078
TI  - Comparative accuracy of the MMPI-2 and the MMPI-A in the diagnosis of
      psychopathology in 18-year-olds.
AB  - Both the Minnesota Multiphasic Personality Inventory--2 (MMPI-2) and the
      Minnesota Multiphasic Personality Inventory--Adolescent (MMPI-A) may be
      administered to 18-year-olds. Each test was administered to 18-year-old
      participants classified as psychopathology present (PP) or psychopathology absent
      (PA) to assess (a) the degree of correspondence between the 2 test versions in
      yielding clinically elevated or nonclinically elevated profiles and (b) the
      relative accuracy of the 2 test versions in identifying the presence of
      psychopathology. The 2 tests produced profiles that were inconsistent in clinical
      elevation status in 70 of 152 participants (46%). All 70 participants with
      incongruent profiles had clinically elevated MMPI-2 scores and normal-range MMPI
      A scores. Analyses of incongruent profiles obtained by PP and PA participants
      indicated that 18-year-olds were overpathologized by the MMPI-2 and
      underpathologized by the MMPI-A.

PMID- 12056079
TI  - Screening for feigned psychiatric symptoms in a forensic sample by using the MMPI
      2 and the structured inventory of malingered symptomatology.
AB  - Fifty-five men undergoing pretrial psychological evaluations for competency to
      stand trial or criminal responsibility in the federal justice system were
      administered the Structured Interview of Reported Symptoms (SIRS), the Minnesota
      Multiphasic Personality Inventory--2 (MMPI-2), and the Structured Inventory of
      Malingered Symptomatology (SIMS). On the basis of results from the SIRS, 31 were
      classified as honest responders and 24 as feigning. Significant differences
      between the 2 groups were found on all SIMS scales as well as on all tested MMPI
      2 fake bad validity scales. The SIMS total score and the MMPI-2 Backpage
      Infrequency (Fb) scale had relatively high negative predictive power (100% and
      92%, respectively). On the basis of this clinically relevant methodology, both
      tests have potential usefulness as screens for malingering.

PMID- 12056080
TI  - The detection of feigned mental disorders on specific competency measures.
AB  - Psychologists have standardized competency-to-stand-trial (CST) assessments
      through the development of specialized CST measures. However, their research has
      largely neglected the possibility that CST measures may be stymied by feigning
      mental disorders and concomitant impairment. The current study is the first
      systematic examination of (a) how feigned mental disorders may affect CST
      measures and (b) which scales are effective at identifying feigned cases. Bona
      fide patients (n = 65) were compared with suspected malingerers (n = 22) on 3 CST
      measures: the Georgia Court Competency Test (GCCT), the MacArthur Competence
      Assessment Tool--Criminal Adjudication, and the Evaluation of Competency to Stand
      Trial--Revised (ECST-R). Results indicated that these CST measures are vulnerable
      to feigning. The development of specialized GCCT and ECST-R scales yielded
      moderately effective screens for feigned mental disorders in the context of CST
      evaluations.

PMID- 12056081
TI  - Cognitive psychometrics: assessing storage and retrieval deficits in special
      populations with multinomial processing tree models.
AB  - This article demonstrates how multinomial processing tree models can be used as
      assessment tools to measure cognitive deficits in clinical populations. This is
      illustrated with a model developed by W. H. Batchelder and D. M. Riefer (1980)
      that separately measures storage and retrieval processes in memory. The validity
      of the model is tested in 2 experiments, which show that presentation rate
      affects the storage of items (Experiment 1) and part-list cuing hurts item
      retrieval (Experiment 2). Experiments 3 and 4 examine 2 clinical populations:
      schizophrenics and alcoholics with organic brain damage. The model reveals that
      each group exhibits deficits in storage and retrieval, with the retrieval
      deficits being stronger and occurring more consistently over trials. Also, the
      alcoholics with organic brain damage show no improvement in retrieval over
      trials, although their storage improves at the same rate as a control group.

PMID- 12056082
TI  - Actual versus self-reported scholastic achievement of litigating postconcussion
      and severe closed head injury claimants.
AB  - Psychologists typically rely on patients' self-report of premorbid status in
      litigated settings. The authors examined the fidelity between self-reported and
      actual scholastic performance in litigating head injury claimants. The data
      indicated late postconcussion syndrome (LPCS) and severe closed head injury
      litigants retrospectively inflated scholastic performance to a greater degree
      than nonlitigating control groups. The LPCS group showed the highest magnitude of
      grade inflation, but discrepancy scores did not significantly correlate with a
      battery of malingering measures or with objective cerebral dysfunction. These
      findings support previous studies, which showed self-report is not a reliable
      basis for estimation of preinjury cognitive status. Retrospective inflation may
      represent a response shift bias shaped by an adversarial context rather than a
      form of malingering.

PMID- 12056083
TI  - Convergent validity of the Agnew Relationship Measure and the Working Alliance
      Inventory.
AB  - The convergent validity of the Agnew Relationship Measure (ARM) and the Working
      Alliance Inventory (WAI) was assessed in samples drawn from 2 comparative
      clinical trials of time-limited psychotherapies for depression. In 1 sample,
      clients (n = 18) and therapists (n = 4) completed self-report versions of both
      measures after every session (n = 198). In the other sample, clients (n = 39) and
      therapists (n = 6) completed the ARM, and observers subsequently rated selected
      audiotaped sessions (n = 78) using the WAI. In both samples, the ARM's core
      alliance scales (Bond, Partnership, and Confidence) were correlated with the
      WAI's scales (Bond, Tasks, and Goals) strongly when assessed within client and
      therapist perspectives and, with some qualifications, moderately when assessed
      between client, therapist, and observer perspectives, supporting the assumption
      that the ARM and the WAI measure some of the same core constructs.

PMID- 12056085
TI  - Falling, entrapment, or crushing could result from toddler access to controls on
      Hard Doernbecher Crib.

PMID- 12056084
TI  - Investigating the validity of the Draw-A-Person: Screening Procedure for
      Emotional Disturbance: a measurement validation study with high-risk youth.
AB  - This validity study examined the extent to which the Draw-A-Person: Screening
      Procedure for Emotional Disturbance (DAP:SPED; J. A. Naglieri, T. J. McNeish, &
      A. N. Bardos, 1991) was a significant predictor of behavioral functioning within
      a clinical sample of 68 latency-age children (6-12 years old) receiving
      counseling services at outpatient and residential treatment facilities. Study
      results showed that the total DAP:SPED (man, woman, and self scores summed) was a
      significant predictor in explaining variation in internalizing behavioral
      disturbance. Specifically, the DAP:SPED remained a moderate strength predictor of
      internalizing behavioral disturbance after controlling for the Child and
      Adolescent Adjustment Profile parent-report behavioral measure. Findings lend
      preliminary support to the DAP:SPED's validity in providing assessment
      information about child behavioral functioning. Continued validation
      investigation along these lines is recommended.

PMID- 12056086
TI  - [Hydronephrosis arterial hypertension. Report of 4 cases].
AB  - Four cases of ureteropelvic junction syndrome associated with arterial
      hypertension were reported. The authors discuss the ethiopathogenic of
      hypertension, on the basis of these observations and a review of the literature.
      They conclude that union bilateral hydronephrosis can lead to hypertension and
      renal failure by both inappropriate production of renin and water chronic
      retention. The correction of ureteropelvic junction should return blood pressure
      to normal levels.

PMID- 12056087
TI  - [Surgical complications of nephrectomy in living donors].
AB  - Renal transplantation from a living donor is now considered the best treatment
      for chronic renal failure. We reviewed the operative complications in 38 living
      related donor nephrectomies performed at our institution over the past 14 years.
      The mean age of our donors was 30 years old with age range between 18 and 58
      years old and female predominance (55.2%). These swabs were realized by a
      posterolateral lumbar lombotomy with resection of the 11 third. The left kidney
      was removed in 34 donors (90%), surgical complications were noted in 39.4% of the
      cases: one case of wound of inferior vena cava (2.6%), one case of release of the
      renal artery clamp (2.6%), four cases of pleural grap (10.5%), one case of
      pneumothorax (2.6%), one case of pleurisy (2.6%), three cases of urinary
      infection (7.8%), three cases of parietal infection (7.8%) and one case of
      patient pain at the level of the wound (2.6%). There were no mortalities. We
      conclude that the morbidity of living donor nephrectomy is negligible compared
      with the advantages for the recipient.

PMID- 12056088
TI  - [Arterial reconstruction with detubulated aortic patch in simultaneous kidney
      pancreas transplantation].
AB  - Simultaneous pancreas kidney transplantation has become an accepted therapy for
      the treatment of patients with insulino-dependant diabetes and renal chronic
      failure. The arterial arrangement of the pancreatic graft is necessary in order
      to avoid surgical complications of vascular thrombosis. We reported three cases
      of simultaneous pancreas kidney, a simple procedure using aortic arterial patch
      preleved with the superior mesenteric artery and detubulated, than the splenic
      artery is directly anastomosed to the patch.

PMID- 12056089
TI  - [Retroperitoneal fibrosis. Report of 6 cases].
AB  - The authors report six cases of retroperitoneal fibrosis. The mean age is 32
      years. Two patients were treated by corticosteroid and ureteric stents with a
      good outcome; they have normal kidney function. Four patients underwent
      ureterolysis by wrapping the ureters in omentum. The mean follow-up is 60 months.
      In the light of theses six cases and review of the literature, the clinical,
      diagnosis and therapeutic aspects are discussed.

PMID- 12056090
TI  - Long-term results of Burch colposuspension and anterior colpoperineorraphy in the
      treatment of stress urinary incontinence and cystocele.
AB  - OBJECTIVE: Female urinary incontinence and bladder prolapse are very common
      conditions whose treatment is not standardized. The aim of this study was to
      evaluate retrospectively the long-term results of Burch colposuspension and
      anterior colpoperineorrhaphy in the treatment of stress urinary incontinence
      (SUI) and cystocele, respectively. MATERIALS AND METHODS: We reviewed 36 female
      patients with a mean follow-up of 53 months. Mean patient age at time of surgery
      was 57.3 +/- 9.6 years (range 37-76). All patients were submitted to urodynamic
      investigation. Anterior colpoperineorrhaphy was performed in 18 cases (13 with
      cystocele, one with SUI and four with both). Burch colposuspension was performed
      in 14 cases (six with SUI and eight with both cystocele and SUI). The association
      of the two surgical procedures was used in four cases with both cystocele and
      SUI. RESULTS: Satisfactory results, such as disappearance of SUI with Burch
      colposuspension and cystocele with colpoperineorrhaphy, were obtained in the
      88.8% and 85.8% of the cases, respectively. These results are even more excellent
      considering that 22.5% of the patients failed previous surgery. We observed no
      significant complications. CONCLUSIONS: The high percentage of long-term success
      confirms that anterior colpoperineorrhaphy and Burch colposuspension are two
      effective therapeutic choices for cystocele and SUI, respectively. The new mini
      invasive techniques have to be compare with these traditional surgical treatments
      which efficacy is consolidated.

PMID- 12056091
TI  - [Non-metastatic prostate cancer treated with exclusive radiotherapy: prognosis of
      patients according to lymph node radiologic or surgical assessment method.
      Multivariate retrospective analysis].
AB  - PURPOSE: To compare retrospectively the outcome of localized prostate cancers
      treated by curative external radiotherapy in which the negative lymphatic status
      was either surgically or radiologically assessed. METHODS AND MATERIALS: From
      January 1986 to December 1995, 112 patients with localized prostate cancers were
      found to have no evidence of lymphatic disease in the pelvis. N0 status was
      assessed either surgically (61 patients, group pN-) or after a CT scan procedure
      (51 patients, group cN0). The treatment consisted of conventional external
      radiotherapy using a four-fields box technique to a total dose of 65 Gy. The
      pelvis was never irradiated. RESULTS: The two groups did not statistically differ
      according to age, PSA level, Gleason score, T stage and hormonal therapy.
      Actuarial NED survival rates were 80% and 60% at five and ten years respectively.
      At ten years, the actuarial NED survival rates were 78% and 34% in the pN- and
      cN0 groups respectively (p = 0.003). The multivariate analysis corroborated the
      positive impact of lymphatic dissection before radiotherapy on disease free
      survival of T1-T2 patients, but not for T3 stages. CONCLUSIONS: This
      retrospective study suggests the inability of CT scan to accurately evaluate the
      lymph node status in carcinoma of the prostate. Systematic ilio-obturator nodal
      dissection is strongly recommended in early stages before curative radiotherapy.
      Only pN-patients should be included in high dose conformal irradiation trials.

PMID- 12056092
TI  - [Anatomoradiologic correlations in prostate benign hypertrophy. Report of a
      series of 220 cases].
AB  - In our daily practice, the reliability of ultrasonography (US) and digital rectal
      examination (DRE) is limited by many factors. The aim of our study is to
      correlate between the prostatic volume assessed by the DRE, the pre operative US
      results and the actual weight of the enucleated or endoscopic resection benign
      prostatic hyperplasia (BPH). We report a serie of 220 patients with BPH treated
      by endoscopic resection or by open surgery. The mean age is 65 years (40-90 years
      old). Ultrasonography was performed in 92% of the cases, and transrectal
      ultrasound only in 8%. All our patients either underwent endoscopic resection
      (49.6%) or adenomectomy (50.4%). We found a high correlation between the
      prostatic volume assessed by DRE and by ultrasonography (r = 0.79; P < 0.0001)
      and the weight of the piece of surgical adenomectomy (r = 0.701, P < 0.0001).
      However, the volume of benign prostatic hyperplasia assessed by US did not
      correlate with the piece of endoscopic resection (r = 0.214, P < 0.05). This
      study and a review of recent literature enabled us to notice the various
      anatomical and radiological factors implicated in this correlation.

PMID- 12056093
TI  - [Modified Duplay technique in the treatment of hypospadias. Report of 585 cases].
AB  - The surgical repair of anterior hypospadias depends on the surgeon's custom and
      the anatomical variations of this anomaly. However, most publications agree
      nowadays on the one-stage surgery. We report on 585 hypospadias operated in our
      department. Our procedure is based on the Duplay technique, in addition to
      personal modifications in order to correct the frequently associated penis
      anomalies. The procedure is described herein. Aesthetic and functional results
      are reported and seem to be very satisfactory in comparison with the literature
      and permit the homologation of our technique.

PMID- 12056095
TI  - [Genital Buschke Loewenstein tumors. Report of 4 cases].
AB  - The authors present four cases of Buschke Loewenstein tumor. In three cases, the
      outcome was good despite areas of anaplasic change are seen in one of them. The
      outcome of the fourth patient was fatal because of multiples recurrences.
      Clinical features, diagnosis and treatment of this rare disease are discussed.

PMID- 12056094
TI  - [Anatomic study of pelvic urethra in women: value of its conservation in radical
      cystectomy].
AB  - The vascularization of the different layers of the pelvic urethra was studied in
      12 females urethras, in which the vascular system was injected with gelatinous
      inda ink. The arterial vascularization of the striated muscle is essentially
      tributary of the sub-mucosal network by the intermediary of fascicular and
      interfascicular arteries which anastomose to form an intermuscular plexus. This
      plexus also anastomoses with the subserosal network. The submucosal layer is a
      true vascular crossroad form by an intricate plexus of blood vessel, both
      arterial and veinuous. The sympathic, para-sympathic and somatic voluntary's
      nerves supply to the pelvic urethra.

PMID- 12056096
TI  - [Bilateral malignant non-Hodgkin's lymphoma].
AB  - Non Hodgkin's lymphoma (NHL) of the testis in young patient are rare. Bilateral
      involvement varies from 5 to 20% of cases and has a negative prognosis. The
      authors report a case of bilateral non Hodgkin's lymphoma of the testis in a 35
      year old man. The patient died six months after the diagnosis.

PMID- 12056097
TI  - [Role of the urologist in the management of infertile men at the time of sperm
      intracytoplasmic injection].
AB  - Although intracytoplasmic sperm injection (ICSI) revolutionized treatment and
      prognosis of male infertility, checkup (case history, clinical and paraclinical
      examinations) practiced by urologist in infertile man keeps all its place.
      Varicocele, congenital or acquired seminal duct obstruction, urogenital tract
      infection, or ejaculation disorder must be sought, because these affections
      remain accessible to treatment.

PMID- 12056099
TI  - Malignant ascites: demographics, therapeutic efficacy and predictors of survival.
AB  - Demographics, treatment patterns, treatment efficacy and clinical predictors of
      survival were studied in 76 consecutive patients with malignant ascites. Sixty
      four percent of patients were female, and mean age was 63 years. The most common
      primary malignancies were ovarian cancer, carcinoma of unknown primary, breast
      cancer, colorectal carcinoma and lymphoma. Ascites was present at the time of
      diagnosis of malignancy in 39%. Diuretics were administered in 22% of patients
      with a 22% response in ascites; all responding patients had hepatic metastases.
      Systemic anticancer therapy was administered in 38%, with a 38% objective
      response in ascites. Five peritoneovenous shunts were placed, with one shunt
      functional at 2 weeks. Paracentesis was performed in 71% of patients with
      complications potentially due to paracentesis occurring in 24% of these patients.
      Median survival was 78 days from the clinical diagnosis of ascites. Multivariate
      analysis revealed significantly shortened survival in patients with liver
      metastases and elevated serum bilirubin, while ovarian cancer was a significant
      independent predictor of prolonged survival.

PMID- 12056098
TI  - Dexrazoxane cardioprotection for patients receiving FAC chemotherapy: a
      pharmacoeconomic evaluation.
AB  - Anthracyclines are among the most effective and commonly-prescribed antitumor
      agents but have dose-limiting cumulative cardiotoxicity. We performed a
      pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac
      related adverse events in patients with Stage IIIB or IV metastatic breast cancer
      who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil,
      doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively.
      Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment.
      We determined the cost of each cardiac event prevented and the cost of each
      additional life-year saved by dexrazoxane use. The cost per cardiac event
      prevented was CDN $5745 and the cost per additional life-year saved was CDN
      $2856. With the increasing use of anthracyclines in Stages I and II breast
      cancer, these favorable clinical and economic results may broaden the range of
      therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy
      of breast cancer.

PMID- 12056100
TI  - Transporting efficacious treatments to field settings: the link between
      supervisory practices and therapist fidelity in MST programs.
AB  - Validated a measure of clinical supervision practices, further validated a
      measure of therapist adherence, and examined the association between supervisory
      practices and therapist adherence to an evidence-based treatment model (i.e.,
      multisystemic therapy [MST]) in real-world clinical settings. Evidence of
      linkages between supervisor adherence to the MST supervisory protocol, as
      assessed through therapist reports, and therapist adherence to MST principles, as
      assessed through caregiver reports, was obtained from 285 families of youths
      presenting serious clinical problems, and 74 therapists and 12 supervisors of 16
      teams in 9 organizations providing MST across 3 states. The findings provide a
      valuable step in examining the determinants of therapist fidelity to complex
      treatments in real-world clinical settings.

PMID- 12056101
TI  - Development of the Therapy Procedures Checklist: a therapist-report measure of
      technique use in child and adolescent treatment.
AB  - Evaluated the psychometric properties of the Therapy Procedures Checklist (TPC).
      The TPC was developed to assess therapists' reports of the techniques they employ
      when working with child and adolescent clients. TPC items encompass the 3 most
      common therapeutic models for youth: psychodynamic, cognitive, and behavioral. In
      a survey of youth therapy experts, TPC items had good content validity for these
      dimensions. Factor analyses of TPC reports from 274 therapists produced the same
      3-factor structure. TPC scales had good internal consistency (all alpha > .86)
      and test-retest reliability (all r > .79) across samples. In a sample of
      practicing therapists, TPC scales were sensitive to within-therapist changes in
      technique use and revealed that therapists increased their use of behavioral
      techniques with young, externalizing child clients. The findings suggest the TPC
      may be a psychometrically sound measure and a useful assessment tool in youth
      therapy research.

PMID- 12056102
TI  - The Target Symptom Rating: a brief clinical measure of acute psychiatric symptoms
      in children and adolescents.
AB  - Describes the development and psychometric properties of the Target Symptom
      Rating (TSR), a brief, multi-informant measure of commonly observed symptoms in
      child and adolescent clinical work. In a large sample of children and adolescents
      in inpatient and residential treatment, the 13 TSR items fell into 2 subscales:
      Emotional Problems and Behavior Problems, which were associated in expected ways
      with the Internalizing and Externalizing factors of the Achenbach scales and the
      Child and Adolescent Functional Assessment Scale (CAFAS). The measure was
      sensitive to change in brief and extended treatment, as rated by parents,
      patients, primary clinicians, and family therapists, and shows promise as a tool
      for outcome research in applied settings.

PMID- 12056103
TI  - Parent-directed physical aggression by clinic-referred youths.
AB  - Identified children and young adolescents who engaged in parent-directed physical
      aggression from a sample of youths referred for outpatient therapy (N = 606, 151
      girls, 455 boys); examined the frequency, severity, and characteristics of such
      behavior; and compared aggressive youths with nonaggressive youths across several
      domains of functioning. Twelve percent of the children and young adolescents in
      this clinical sample engaged in parent-directed aggression. Aggressive, compared
      to nonaggressive, youths had significantly increased oppositional behavior, lower
      frustration tolerance, less adaptability to stressful situations, and were more
      demanding of their parents. Aggressive children had families characterized by
      significantly greater parental stress, poorer interpersonal relationships, and
      were more likely to be 2-parent, European American families of higher
      socioeconomic status. Moreover, lower frustration tolerance and adaptability were
      significant predictors of parent-directed aggression after controlling for
      demographic differences and overall level of oppositionality and aggressiveness,
      suggesting a more specific functional impairment in such children. Parent
      directed aggression warrants additional study given the limitations in our
      understanding of these events and the potential for such behaviors to continue
      into adolescence and adulthood.

PMID- 12056104
TI  - Adolescent peer relationships and mental health functioning in families with
      domestic violence.
AB  - Examined the impact of domestic violence, child abuse, and attachment style on
      adolescent mental health and relationship functioning. Data were collected on 111
      adolescents, ages 14 to 16, and their mothers. Results indicate that both
      attachment and family violence experiences negatively impact mental health. In
      addition, family violence significantly predicted attachment style. Significant
      protective and vulnerability factors included maternal psychological functioning,
      maternal positive parenting, and perceived social support from friends. However,
      findings provided only limited support for the model of attachment as a mediator
      of the impact of family violence on adolescent relationships.

PMID- 12056105
TI  - Problem-solving orientation and attributional style: moderators of the impact of
      negative life events on the development of depressive symptoms in adolescence?
AB  - Followed up 733 adolescents, ages 12 to 14 years, from a community sample over a
      1-year period. Depressive symptoms at 1-year follow-up, controlling for baseline
      depression levels, were predicted by negative life events (NLEs) in the previous
      12 months, attributional style (AS), negative problem solving orientation (NPSO),
      and the interaction between NLEs and NPSO. In the presence, but not absence, of
      high NLEs, NPSO predicted increases in depressive symptoms. In contrast,
      pessimistic AS predicted future increases in depression irrespective of the
      occurrence of NLEs. The findings supported a congnitive diathesis-stress model of
      the development of depression for NPSO but not AS.

PMID- 12056106
TI  - Are the performance overestimates given by boys with ADHD self-protective?
AB  - Tested the self-protective hypothesis that boys with attention deficit
      hyperactivity disorder (ADHD) overestimate their performance to protect a
      positive self-image. We examined the impact of performance feedback on the social
      and academic performance self-perceptions of 45 boys with and 43 boys without
      ADHD ages 7 to 12. Consistent with the self-protective hypothesis, positive
      feedback led to increases in social performance estimates in boys without ADHD
      but to decreases in estimates given by boys with ADHD. This suggests that boys
      with ADHD can give more realistic self-appraisals when their self-image has been
      bolstered. In addition, social performance estimates in boys with ADHD were
      correlated with measures of self-esteem and positive presentation bias. In
      contrast, for academic performance estimates, boys in both groups increased their
      performance estimates after receiving positive versus average or no feedback, and
      estimates were not correlated with self-esteem or social desirability for boys
      with ADHD. We conclude that the self-protective hypothesis can account for social
      performance overestimations given by boys with ADHD but that other factors may
      better account for their academic performance overestimates.

PMID- 12056107
TI  - Response inhibition, hyperactivity, and conduct problems among preschool
      children.
AB  - Investigated the relation among response inhibition, hyperactivity, and conduct
      problems in a nonclinical sample of 115 preschool children, using 2 different
      types of go/no-go tasks well as a Stroop-like task. In line with the assumption
      that hyperactivity is related to disinhibition, the results showed that it was
      the measures of response inhibition, and not other performance measures, that
      were related to teacher ratings of hyperactivity. There was also a significant
      relation between response inhibition and conduct problems. Interestingly, the
      correlation between response inhibition and conduct problems was not significant
      when partialling out the effect of hyperactivity, whereas the correlation between
      inhibition and hyperactivity did remain significant when controlling for conduct
      problems. Although the association between inhibition, hyperactivity, and conduct
      problems appeared to be partly different for boys and girls, these differences
      were not statistically significant.

PMID- 12056108
TI  - Comparing measures of childhood loneliness: internal consistency and confirmatory
      factor analysis.
AB  - Compared 6 self-rating measures of loneliness and associated phenomena, designed
      for use with elementary-school children. Three samples of children in Grades 5
      and 6 (total N = 758) completed various combinations of these instruments. In
      terms of internal consistency, the Children's Loneliness Scale (CLS) and the peer
      related loneliness subscale of the Loneliness and Aloneness Scale for Children
      and Adolescents (LACA) were most reliable. Substantial support was obtained for
      the convergent validity of the measures. Confirmatory factor analysis (CFA) on 2
      samples and exploratory factor analysis on a third sample indicated that the 13
      scales and derivative subscales of the 6 measures tapped 4 different but
      interrelated latent constructs: peer-related loneliness, family-related
      loneliness (in some cases restricted to parent-related loneliness), negative
      attitude toward being alone, and positive attitude toward being alone.
      Recommendations are offered for conditions under which each scale may be useful.
      Limitations of this study are discussed and suggestions for future research are
      offered.

PMID- 12056110
TI  - Parenting styles and child behavior in African American families of preschool
      children.
AB  - Examined the relations between parenting styles and child behavior problems in
      African American preschool children. Participants were 108 African American
      female caregivers of 3- to 6-year-old children. Correlational analysis showed
      that parent-reported child behavior problems were associated with maternal
      education, family income, and parents' endorsement of authoritative parenting,
      authoritarian parenting, and permissive parenting. Hierarchical regression
      analysis showed that the authoritative parenting style was most predictive of
      fewer child behavior problems. These results are consistent with previous
      findings with European American families and provide strong support for the cross
      cultural validity of the authoritative parenting style.

PMID- 12056109
TI  - The Guide to the Assessment of Test Session Behavior: validity in relation to
      cognitive testing and parent-reported behavior problems in a clinical sample.
AB  - Examined the validity of the Guide to the Assessment of Test Session behavior
      (GATSB) in a clinical sample. The GATSB is a structured and standardized measure
      that was normed on the Wechsler Intelligence Scale for Children-Third Edition
      (WISC-III) standardization sample. The purpose of this study was to extend
      validity research on the GATSB to cognitive measures other than the WISC-III and
      to parent-reported child behavior problems. Test observations were taken for 122
      children ages 6 to 16 years who were referred to an outpatient psychology clinic
      for psychoeducational evaluations. GATSB scores demonstrated a moderate relation
      with general indexes from the WISC-III, the Woodcock-Johnson Psychoeducational
      Battery-Revised (WJ-R), and the Wide Range Assessment of Memory and Learning
      (WRAML), but displayed low magnitude correlations with the Child Behavior
      Checklist (CBCL). These results expand existing data supporting the validity of
      the GATSB and suggest that it may be fruitfully adopted into a clinic setting.

PMID- 12056111
TI  - Analysis of variance frameworks in clinical child and adolescent psychology:
      advanced issues and recommendations.
AB  - Explores more advanced issues that researchers need to consider when using
      analysis of variance frameworks, building on basic issues for analysis of
      variance discussed in Jaccard and Guilamo-Ramos (2002). These include (a) using
      confidence intervals, (b) asserting group equivalence after a nonsignificant
      result, (c) use of magnitude estimation approaches, (d) sample size and power
      considerations, (e) outlier analysis, (f) violations of assumptions, and (g)
      missing data. Suggestions are offered for analytic practices in each of these
      domains.

PMID- 12056112
TI  - Selected abstracts from the 9th Annual Retrovirus Conference.

PMID- 12056113
TI  - AIDS and its progress in a patient taking--and not taking--medication.

PMID- 12056114
TI  - The HIV specialist improves quality of care and outcomes.
AB  - HAART has raised the bar for standards of care for HIV/AIDS. As patient outcomes
      improve, efforts are under way to address the infrastructure needed to continue
      to provide high-quality HIV care. Standards of care and treatment guidelines are
      updated regularly in an effort to keep up with our rapidly evolving understanding
      of HIV medicine. Two professional organizations have been formed in the past
      several years to address the needs of HIV care providers and patients. While
      there is slight variation between the 2 groups, both organizations define the HIV
      specialist in terms of clinical experience and continuing education and recognize
      that HIV care providers are a diverse group committed to managing this critical
      and constantly evolving epidemic. Several states have also developed initiatives
      that address the importance of health care quality and outcomes for people with
      HIV/AIDS. New York and California lead the way, and surely other states will
      follow. To ensure quality of care and continued good outcomes for our patients,
      managed care organizations and other providers of HIV care can now measure their
      own competence against these existing standards.

PMID- 12056115
TI  - Disseminated Paecilomyces lilacinus infection in a patient with AIDS.
AB  - We describe a case of disseminated Paecilomyces lilacinus infection occurring in
      a patient with advanced HIV infection. P lilacinus is a ubiquitous environmental
      fungus that has been associated with infection in various immunocompromised
      hosts, in patients with invasive medical devices, and in contact-lens wearers.
      The clinical features, morphologic characteristics, and response to antifungal
      therapy in our patient are similar to findings reported in disseminated infection
      due to Penicillium marneffei, another opportunistic fungal infection in HIV
      infected patients. We believe this to be the first report of infection with P
      lilacinus in a patient with AIDS.

PMID- 12056116
TI  - Who are the heroes?

PMID- 12056117
TI  - How legislation has historically helped nursing when in crisis point.
AB  - Health is a political issue. Healthcare is political because it is integral to
      development. Health-related services must be a part of socioeconomic plans
      developed at the national level. Nurses are directly influenced by these matters.
      Recruitment, retention, education and practice of nurses are affected by the
      demand for services, reimbursement systems, prevalent healthcare problems, and
      research findings.

PMID- 12056118
TI  - Legislation is the solution to the nursing shortage. The con side.

PMID- 12056119
TI  - Interview with representative Eddie Bernice Johnson. Interview by Harriet R.
      Feldman.

PMID- 12056120
TI  - Provider leadership style and view of patient compliance.
AB  - The term "compliance" came into the nursing language from the language of
      medicine. Definitions of compliance range from patients' obeying providers'
      orders to patients determining desired health outcomes and treatment goals. A
      historical perspective of this term provides a framework for discussion of
      approaches to compliance identified from the research literature. This review
      draws an analogy between these approaches and leadership styles and raises the
      question about what role provider style plays in patient compliance.

PMID- 12056122
TI  - The uninsured.

PMID- 12056121
TI  - Unpacking the elephant.

PMID- 12056123
TI  - The future of medicine: peering into the crystal ball.

PMID- 12056124
TI  - Educating physicians: a TMA primer, Part 2.

PMID- 12056126
TI  - TMA files class action lawsuits against insurance companies.

PMID- 12056125
TI  - Training and experience.

PMID- 12056127
TI  - TMA alerts members to BME discipline of X-ray violations.

PMID- 12056128
TI  - Medicare fracture data for the state of Tennessee, 1994-1998.

PMID- 12056129
TI  - Reactive airways dysfunction syndrome following metal fume fever.
AB  - Metal fume fever (MFF) is an acute response to the inhalation of heavy metals
      used in industry. The patient typically experiences symptoms of cough, fever,
      chills, malaise, and myalgia that are self-limited and of short duration.
      Wheezing may occur and pulmonary function may be acutely impaired with a decrease
      in lung volumes and diffusing capacity of carbon monoxide. Nevertheless,
      respiratory function quickly returns to normal, and persistent pulmonary
      insufficiency is unusual. Irritant-induced asthma is a non-immunogenic form of
      airway injury that may be associated with industrial inhalation exposure. In this
      situation, the direct toxic effect on the airways causes persistent airway
      inflammation and bronchial hyperreactivity. The two conditions are considered
      distinct entities, but we report a previously healthy worker who had classic MFF
      and was left with irritant-induced asthma or reactive airways dysfunction
      syndrome (RADS).

PMID- 12056130
TI  - State mandates reporting of unusual incidents and medical errors.

PMID- 12056131
TI  - Exceptions to the "hearsay" rule: family abuse, the role of the court, police,
      and the health care provider.

PMID- 12056132
TI  - [Relationship between biochemical parameters of blood in residents of the
      European North with mandibular fractures and nutrition].
AB  - Study of the qualitative and quantitative composition of the "mandibular" diet in
      66 residents of the European North with mandibular fractures showed its
      deficiency, which led to delayed consolidation of the fractures. Use of
      individual balanced rations including calcium alginate in 68 patients led to more
      rapid consolidation of fractures and accelerated recovery of the patients'
      working capacity.

PMID- 12056133
TI  - [Clinical factors essential for dental caries intensity in rheumatic patients].
AB  - A total of 349 patients with rheumatoid arthritis, 129 with systemic lupus
      erythematosus, and 92 with systemic scleroderma were examined. A higher incidence
      of caries (CDL index) in comparison with the norm (p < 0.05) was observed in all
      patients; the most significant factor promoting caries development was
      involvement of the salivary glands presenting as Sjogren's syndrome (p < 0.005).
      The presence and severity of temporomandibular involvement virtually did not
      affect the intensity of caries (p > 0.1). The highest CDL index was observed in
      patients with rheumatoid arthritis and systemic scleroderma with pronounced
      dysfunction of the hand joints (p < 0.01) and higher activity of disease (a
      higher percentage of patients with Sjogren's diseases of the second and third
      degrees of activity) (p < 0.05). These data confirmed the multifactorial nature
      of dental caries etiology in rheumatic diseases.

PMID- 12056135
TI  - [Pathogenetic validation of xidiphone use in combined therapy for periodontal
      diseases].
AB  - It is well grounded for the application of a preparation from group
      bisphosphonates xydiphone is justified (reasonable). For treatment and preventive
      maintenance of a tooth stone for want of periodontal inflammation. Is shown on 30
      patients with acute parodontitis and at 10--with gingivitis (in a stage of a
      peaking), that the application of xydiphone will neutralize an alkaline response
      having a place up to treatment, due to what it(he) exhibits antiseptic of a
      property. Xydiphone, linking ionized Ca and free Fe, simultaneously hinders with
      activation of free--radical oxidation, reduces blood-flux and blocks process of
      crystallization.

PMID- 12056134
TI  - [Antioxidant Mexidol premedication of patients with periodontitis during
      antihomotoxic therapy].
AB  - The tranquilizing effect of antioxidant mexydol on 95 patients with chrconic
      generalized parodontitis against a background of various somatic diseases was
      evaluated. The anxiety and the efficiency of premedication were accessed
      according to Korach's and Spilberger's scales and according to the special
      psychological questionnaire. The quantitative characteristics of premedication
      were given baised on the psychological tests results. There was registered a
      definite improvement of health characteristics and of patient's mood in
      comparison to the initial input data as well as lower lever of their situational
      anxiety. This proves the tranquilizing effect of premedication with mexidol (5%
      amp.). The most evident dynamics of these changes can be observed among patients
      suffering from high initial anxiety level. The findings of the study are based on
      more than 2 year old history of treatment of 30 patients with traumel. 21
      patients suffering from disfunction of the nervous system were given some
      comprehensive treatment (traumel locally orally and mexidol in injections). The
      clinical effect resulted in emotional stabilization of patients and reduced the
      time needed for their clinical treatment. The medicines were combined. No side
      effects were observed.

PMID- 12056136
TI  - [The significance of lipid peroxides for prediction of traumatic mandibular
      osteomyelitis].
AB  - 68 patients with mandible's fractures were observed. There was studied the
      importance of peroxygenation of lipids and antioxydation system for prognosing
      and diagnosing of posttraumatic osteomyelitis of mandible. It was established
      that the intensifies of peroxygenation of lipids increased and the level of
      antioxydation system decreased in cases of mandible's fractures. The patients
      having posttraumatic osteomyelitis afterwards had the more changes in
      concentration of peroxygenation of lipids.

PMID- 12056137
TI  - [Results of prosthetic treatment of the temporomandibular joint at the Central
      Institute of Dentistry].
AB  - Immediate and late results of reconstruction of the temporomandibular joint with
      endoprostheses of the condylar processes are analyzed. Types of condylar process
      endoprostheses are described. The most characteristic complications of the
      immediate and late postoperative periods are described.

PMID- 12056138
TI  - [Use of implants in congenital anodontia].
AB  - Use of screw implants for repair of the maxilla and mandible defects with
      congenital anodontia is discussed. Surgical methods are described. Clinical
      examples are offered. Immediate and remote results are illustrated.

PMID- 12056139
TI  - [Reactive anxiety in patients during orthodontic treatment with crowns].
AB  - Reactive anxiety of patients was evaluated at clinical stages of orthodontic
      treatment with polymeric crowns. Antistress therapy essentially decreased the
      number of patients with high reactive anxiety. Measures to control fear are
      obligatory before tooth preparation and impression making. At the rest stages it
      is hardly necessary to focus the dentist's and patient's attention at these
      measures.

PMID- 12056140
TI  - [Comparative in vitro evaluation of color and color stability of composite and
      ceramic ionomer materials for esthetic repair of teeth].
AB  - Comparative colorimetric evaluation of shades and translucency of different
      samples, fabricated from Filtec Z-250, Unirest, Dyract AP and Vitremer, shows,
      that differences in their compositions and industrial technologies result to
      great differences between the shades of the same number of Vita Shade Guide. The
      less color stability after long term action by foods media to the samples was
      found for the glass ionomer cement. The best color stability was found for
      composites, partially, for Unirest. All of these, let us conclude, that the main
      changes, not only in shades, but in translucency of materials, as a result the
      action of model media, take place at the early periods (the first month).
      Usually, the most main changes in restorative materials take place in this period
      of beginning and connect with the end of setting processes and achieving the
      balances between water absorption and solubility.

PMID- 12056141
TI  - [Clinical and laboratory studies of bacterial adhesion to validate the choice of
      material for making provisional dentures for patients with periodontal diseases].
AB  - Adhesion of bacteria favoring the development of oral inflammations, including
      cariesogenic and periodontopathogenic (Actinobacillus actinomycetemcommitans,
      Streptococcus sanguis, Fusobacterium nucleatum, Staphylococcus warneri) and yeast
      fungi (Candida albicans), to 13 materials used for making provisional dentures
      was studied. Adhesion of all the studied bacteria and fungi to Russian material
      Esterfil Foto was the minimum. Clinical use of this material in patients with
      chronic generalized periodontitis showed that it was well tolerated and the
      treatment led to improvement of oral microbiocenosis.

PMID- 12056142
TI  - [Complex diagnosis of congenital cranial dysostosis in children].
AB  - Ten patients (aged 3-15 years) with congenital cranial dysostosis were examined
      by a pediatrician, geneticist, gastroenterologist, neuropathologist,
      ophthalmologist, endocrinologist, and orthopaedist. In addition to the clinical
      signs characteristic of hereditary multiple developmental defects, the study
      revealed changes in the jaws and temporomandibular joint and local factors
      promoting the progress of deformations of the jaws. Manifest and inapparent
      pathological changes and dysfunctions in gastrointestinal organs were paralleled
      by dysfunctions of the central and autonomic nervous systems, risk of
      maxillofacial and general deformations, and signs of congenital disorders in
      calcium, lactic acid, and pyridoxine metabolism. The results necessitate analyses
      of the blood and urine and development of new methods for the diagnosis of
      congenital cranial dysostosis and improvement of methods for the correction of
      this condition.

PMID- 12056143
TI  - [A case with congenital underdevelopment of the middle part of the face in a
      newborn].
AB  - A newborn is described with a rare developmental defect of the middle part of the
      face: median cleft in the upper lip, alveolar process, hard and soft palate
      combined with pronounced hypotelorism and prosencephalia. Combination with
      hypotelorism indicates that the defect should be classified as a prosencephalic;
      the risk of repeated birth of a child with such a defect can be as high as 25%.

PMID- 12056144
TI  - [Status of the oral organs in children with chronic glomerulonephritis].

PMID- 12056145
TI  - [Monitoring of fluoride levels in children receiving fluorinated milk for a long
      time and time course of their permanent teeth].
AB  - Measurements of fluorine concentrations in 1320 urine samples collected from 440
      children in the city of Maikop showed low levels of fluorine (0.43-0.72 mg) in
      this group in comparison with the groups receiving prophylactic treatment with
      optimal safe doses of fluorine with milk (0.88-1.19 mg). Consumption of
      physiological amounts of fluorine does not lead to its accumulation in the body
      even after long (up to 5 years) consumption of fluorinated milk. Permanent ratio
      between the values in the control and prophylactic groups allows less frequent
      monitoring of fluorine levels: during the first month of prevention and then
      after 2 and 4 years of prophylaxis with fluorinated milk. Clinical evaluation of
      anticaries efficiency of fluorinated milk in 920 children aged 6-8 years (309 in
      the control and 611 in prophylactic groups) showed a significant decrease of
      caries prevalence (by 12.5-24.5%) and intensity in permanent teeth (by 50.6-56.7%
      by the CDL index and by 47.6-52.9% by the CDLp index) after 3-5 years of regular
      consumption of fluorinated milk.

PMID- 12056146
TI  - [Imudon effectiveness in the treatment and prophylaxis of dental caries].

PMID- 12056147
TI  - [Role of mathematical methods in studies of literacy in medicine of the
      population with regard to dentistry].

PMID- 12056148
TI  - [Laryngeal mask in oral surgery in an outpatient setting].

PMID- 12056149
TI  - [An uncommon clinical manifestation of the sublingual salivary gland cyst].
AB  - A female patient with ranula (cyst of the sublingual salivary gland) without
      characteristic clinical signs of ranula in the oral cavity is described. The
      diagnosis was made only during intervention.

PMID- 12056150
TI  - [Method for measuring dental roots by roentgenograms for making experimental
      models].
AB  - Two methods were used for measuring the true size of abutment teeth roots for
      making experimental models. One method was based on the use of intraoral contact
      roentgenograms made with a Russian 5D-2 x-ray diagnostic dental device and the
      other on the use of roentgenograms made with parallel beam bundles from a longer
      distance using an x-ray diagnostic dental device with a more potent x-ray tube,
      Evolution-300 (Italy) on a Kodak x-ray film (USA) Ultra-speed-58, 3.1[symbol: see
      text]4.1 cm. The results obtained by the latter method are more accurate, the
      difference from the true size being no more than 0.5 mm. However intraoral
      contact roentgenograms give the results close to the true size of abutment teeth
      roots, for example, for one of the mandibular premolars; however a correction
      coefficient should be used.

PMID- 12056151
TI  - [Diagnostic implications of examination of the middle ear resonance frequency].
AB  - Resonance frequency of the middle ear was examined in 24 persons with normal
      hearing, 10 patients with otosclerosis and 4 patients subjected to
      stapedioplasty. It is shown that shift of the resonance frequency is important
      for differential diagnosis. In particular, in otosclerosis resonance frequency
      shifts to higher values, while in mass increases (rupture of acoustic bones
      chain) there is a shift to lower frequencies.

PMID- 12056152
TI  - [Transcranial duplex scanning in estimation of cerebral hemodynamics in patients
      with secondary cochleovestibular neuritis].
AB  - The authors present pilot experience with transcranial duplex scanning (TCDS) of
      the cerebral vessels in 17 patients with secondary cochleovestibular neuritis
      combined with chronic leptomeningitis (primarily of the posterior cranial fossa).
      This method has determined extra- and intracranial hemodynamics, characterized
      arterial and venous blood flow qualitatively and quantitatively, outlined
      possible genetically determined factors in development of dyscirculatory
      disorders. Finally, hemodynamic defects of two types were revealed in 12
      patients. Type 1 (3 patients) was characterized by asymmetric circulation in the
      territory of the middle, anterior and posterior cerebral arteries, by the absence
      of venous congestion. Type 2 (9 patients) was characterized by impaired venous
      outflow manifesting as higher speed of the blood flow and its phase response
      along the intracranial veins and sinuses. In 7 patients these defects combined
      with asymmetric circulation along brain stem arteries. These patients were
      diagnosed to have perilymphatic labyrinthine hydrops.

PMID- 12056153
TI  - [Biological feedback techniques in rehabilitation of patients with impaired
      equilibrium function].
AB  - Vestibular rehabilitation with application of biological feedback methods has
      been performed in 25 patients with vestibular disorders. In them, an objective
      method of functional computer stabilometry verified equilibrium disturbance.
      Compared to the control group of 30 patients treated conventionally with drugs,
      biological feedback methods proved high effectiveness.

PMID- 12056155
TI  - [Age-specific and etiological aspects of acquired laryngo-tracheal cicatricial
      stenosis in children].
AB  - 453 case histories of children with acquired laryngo-tracheal stenosis (LTS) have
      been analysed. Etiological factors of the disease, age at the moment of
      respiratory lesion, duration of the intubation were examined. LTS developed in
      the majority of patients (58.3%) within the first 3 years of life. At this age
      boys suffer from LTS 2.5 times more frequently than girls. The stenosis was
      caused by tracheal intubation in 86.1% children. The intubation resulted from
      acute stenosing laryngotracheobronchitis (47.5%), craniocerebral trauma (13.2%),
      operations (12.8%), acute pathology of CNS (6.8%). LTS in boys develops 3.1 times
      more frequently in tracheal intubation for acute stenosing
      laryngotracheobronchitis and 2.9 times more frequently in intubation for acute
      CNS pathology. In intubation for other reasons the stenosis rate does not depend
      on the gender. The statistical data obtained by the authors require further
      clinico-immunological investigations.

PMID- 12056154
TI  - [Prevention of postoperative scars in otorhinolaryngology: experimental
      rationale].
AB  - It is demonstrated that in vitro inhibition of fibroblasts proliferation is
      feasible with the use of 5-fluorouracil. In stimulated growth of fibroblasts, the
      antiproliferative effect of 5-fluorouracil manifests even in a minimal
      concentration (2 mcg/ml). Recovery of fibroblast proliferative activity after
      elimination of 5-fluorouracil occurs in concentration under 63 mcg/ml.

PMID- 12056156
TI  - [Functional characteristics of the central nervous system in children with
      pharyngeal tonsil lesions].
AB  - The analysis of the clinical and neurophysiological evidence obtained upon
      examination of children with adenoids has shown that pharyngeal tonsil affection
      is often accompanied by neurological disorders. Perinatal pathology does not
      influence significantly EEG alterations. Surgical treatment leads to positive
      changes of both general condition and neurophysiological indices, but part of the
      children with perinatal encephalopathy worsen because of aggravation of brain
      problems and appearance of epiphenomena. It is thought necessary to consider
      perinatal history when planning treatment policy for children with affection of
      the pharyngeal tonsil.

PMID- 12056157
TI  - [Prevalence and certain characteristics of chronic hyperplastic laryngitis].
AB  - Screening for chronic hyperplastic laryngitis (CHL) has been performed among
      70,000 workers and peasants of the Moscow Region. CHL was detected in 355
      examinees (0.47%). The data were analysed for 166 CHL patients (age 31-50, 87
      males, 29 females). 8 patients had laryngostenosis but tracheostoma was indicated
      only one of them. Malignant transformation occurred in 3 patients. Laryngeal
      lesions were symmetric in 36 patients, unilateral with separate inflammatory
      infiltrates clinically similar to tumors were seen in 45 patients. Local forms of
      CHL may look as separate small nodules, contact lesions in the region of vocal
      processes of the arytenoid cartilages, and diffuse inflammatory edema of the
      vocal cords. In rare cases inflammatory tumor-like laryngeal lesions in CHL
      depend on local flock of lymphoid elements--lymphoid hyperplasias. A cytological
      study in CHL is effective in identification of the signs of dystrophy,
      keratinization and epithelial cell atypia as well as the presence of microflora.

PMID- 12056158
TI  - [Interferon therapy and immunotherapy in children with respiratory
      papillomatosis].
AB  - The ENT clinic of St-Petersburg Pediatric Medical Academy for 15 years admitted
      126 children with respiratory papillomatosis 10 months to 15 years of age. 111 of
      them had laryngeal papillomatosis. The scheme of combined treatment was adjusted
      to interferon status of the patients. Replacement therapy with recombinant
      interferon--viferon--was applied in low production of alpha/beta-interferon but
      high serum interferon. In low serum interferon and intact interferon reserves the
      treatment was combined: interferon inductor--cycloferon plus viferon. In all the
      children the above treatment was given following surgical (microendoscopic)
      removal of laryngeal papillomas. The clinical course of laryngeal papillomatosis
      ran in accordance with changes of interferon status in the majority of cases.

PMID- 12056159
TI  - [Malignant multifocal ENT tumors].
AB  - Of 6787 patients with ENT cancer, multifocal tumors were detected in 319 cases
      (4.7%). 306(95.9%) patients had two tumors, 13(4.1%)--three tumors. Synchronous
      and metachroneous tumors were diagnosed in 39.2 and 60.8% patients, respectively.
      Primary tumors located more frequently in the larynx (n = 146) and pharynx (n =
      50). The second tumors were more often found in the lungs (25.5%), pharynx
      (22.1%), oral cavity (13.2%). In 84.9% patients with multifocal tumors the first
      and the second lesions arose in the same organ system--respiratory and
      gastrointestinal tracts. Metachroneous tumors developed more often 2-5 years
      (49.1%) after cure of the primary tumor.

PMID- 12056160
TI  - [Population characteristics of chronic ENT diseases prevalence in adults living
      in the North of the Eastern Siberia].
AB  - Characteristics of chronic ENT diseases in European migrants and native Mongoloid
      population of the East Siberian North have been analysed epidemiologically.
      Epidemiological differences and similarities between the above populations are
      explained by their immunogenetic peculiarities.

PMID- 12056161
TI  - [ENT chondromas].

PMID- 12056162
TI  - [Drainage of cerebral and cerebellar abscesses with "cigar"-shape draining
      tampon].
AB  - The treatment was given to 95 patients aged 5 to 63 years with temporal (n = 86)
      and cerebellar abscesses (n = 9). Most of the patients were hospitalized after
      home treatment with antibiotics which complicated the diagnosis because of
      atypical course of the disease induced by them. The "cigar" tampon was used for
      draining brain abscess. The cover of the tampon was made not of the glove rubber
      but of a baby's rubber dummy and a rubber pipette cap. Holes were cut in the
      walls of the latter and gauze turundas inserted. The results of such manipulation
      were favourable. Therefore, it is recommended to use a modified "cigar" tampon
      drain in the treatment of otogenic abscesses of the brain and cerebellum.

PMID- 12056163
TI  - [Examination of the olfactory analyzer].
AB  - A method of threshold olfactometry is proposed consisting in the use of three
      olfactive substances (tincture of valerian, acetic acid, liquid ammonia) in
      selected concentrations. This allows to investigate the thresholds of certain
      modality. Each concentration of the olfactive substance is placed into a glass
      bottle (100 ml) and stored at the temperature 18-20 degrees C. The examination of
      the state of the olfactory analyzer within a 24-h working day showed stability of
      threshold olfactometry when the organism is tired. Utilization of threshold
      olfactometry in some diagnostic areas is shown.

PMID- 12056164
TI  - [A case of thyroid ectopy in a 7-year-old girl].

PMID- 12056166
TI  - [Isolated tuberculosis of the maxillary sinus and ethmoidal labyrinth].

PMID- 12056165
TI  - [Foreign bodies in the esophagus and bronchi left after medical manipulations].

PMID- 12056167
TI  - [Angiogenic cochleo-vestibular diseases and dyslipoproteinemia: new insight].

PMID- 12056169
TI  - Prevalence of cardiovascular risk factors of elderly persons in Taiwan.
AB  - Cardiovascular disease has been one of the top-ten causes of death continuously
      for older persons in Taiwan. However, There is still a lack of sufficient
      information on prevalence rates of cardiovascular risk factors. The present study
      was intended to provide prevalence rates of biological and behavioral risk
      factors for cardiovascular disease by gender, age group, and dwelling area. Data
      were extracted from a nationwide, cross-sectional, geriatric survey (1989-1991)
      by four medical centers in Taiwan. A total of 2,600 community senior residents
      were successfully interviewed for analysis. For the whole sample, hypertension
      was found to be the most prevalent biological risk factor (36.9%), while being
      overweight was the first behavioral risk factor (34.38%). By gender, higher
      prevalence rates of biological risk factors were found in older women except for
      the low value of high density lipoprotein cholesterol (HDL-C); higher prevalence
      rates of behavioral risk factors were found in men except for being overweight.
      No statistically significant difference in prevalence rates was found between the
      65-74 and 75+ years age groups. By dwelling area, significant differences in the
      prevalence rates of risk factors existed across the four study areas. In
      conclusion, hypertension and excessive weight are critical cardiovascular risk
      factors that can be early identified or prevented by screening programs and
      health education. Cardiovascular prevention programs for elderly people should be
      designed in their gender and dwelling area.

PMID- 12056168
TI  - [Ototoxic effect and its prevention in administration of cisplatin].
AB  - Short-latent acoustic evoked potentials were registered in examination of hearing
      function in guinea pigs given platinum compounds. A protective action of thiol
      compounds (sodium thiosulfate and unitiol) was tried in relation to hypoacusis
      induced by cisplatinum.

PMID- 12056170
TI  - A comparative study of ocular and generalized myasthenia gravis.
AB  - We compared the relations and therapeutic outcomes of ocular and generalized
      types of myasthenia gravis (MG) and used retrospective analysis for 65 patients
      with myasthenia gravis during a mean follow-up time of 30.4 months. There were 35
      ocular and 30 generalized MG patients. Items of comparison included sex, age,
      clinical presentations, serum antibody titer, the association with thymus status,
      and therapeutic outcome. Of the patients with generalized MG, males were
      significantly older than females. Ptosis and diplopia were the most common
      symptoms in patients with MG, but there were no significant differences between
      the two types of MG. The eyelid levator muscle and lateral rectus muscle were the
      most commonly involved extraocular muscles in patients with MG. The associations
      with thymoma or thymus hyperplasia were more common in generalized MG than in
      ocular MG, and more common in younger than in older patients. The result of
      positive neostigmine test was 93.8% in all patients, but there were no
      significant differences between the two types of MG. Acetylcholine receptor
      antibody (AchRAb) presented an 81.1% positive rate and was significantly higher
      in generalized MG than that in ocular MG (96.2% vs 66.7%). There were no
      significant differences between the two types of MG regarding successful
      treatment strategies in both initial therapy and maintenance therapy. Only two of
      16 patients had complete remissions after thymectomy. From the viewpoint of
      clinical presentations or from the therapeutic strategy outcome, the boundary
      between both types of MG seems to be vague. Both types of MG probably share the
      same entity in nature and the difference is just a matter of degree of severity.
      The benefit of thymectomy in treatment of MG needs further investigation.

PMID- 12056171
TI  - Ultrasonographic findings in hemiplegic shoulders of stroke patients.
AB  - Shoulder problems are frequently noted in hemiplegic shoulders and compromise
      rehabilitation. Many tools were used to evaluate the etiology of shoulder
      problems but most of them are either nonspecific to the evaluation of soft tissue
      or not convenient. In order to evaluate soft tissue and joint change in
      hemiplegic shoulders, 82 patients with hemiplegic shoulders caused by cerebral
      vascular accident (CVA) were collected and evaluated by ultrasonography with 5-12
      MHz high-resolution electronic linear scanner (ATL ultrasound HDI 1500, USA). The
      non-hemiplegic shoulders were also studied as control group. The results showed
      that ultrasonographic changes were noted in 51 (62.2%) hemiplegic shoulders while
      changes only occurred in 17 (20.7%) non-hemiplegic shoulders. Effusion and
      tendinitis were the major changes showing statistical difference compared with
      non-hemiplegic shoulders, but there was no significant difference in the
      incidence of supraspinatus tendon tear between hemiplegic and non-hemiplegic
      shoulders. Further, the interval from the onset of CVA was not significantly
      correlated with the presence of positive ultrasonographic findings in hemiplegic
      shoulders. The results demonstrated that ultrasonography is a potential method in
      the evaluation of hemiplegic shoulder.

PMID- 12056172
TI  - [Gd(DTPA-BDMA)] as a magnetic resonance contrast agent: acute toxicity test and
      preliminary images.
AB  - The new complex of Gd(III) with the 1,7-bis[(N-dimethyl(carbomoyl)methyl)-1,4,7
      triazaheptane-1,4,7- triacetate[Gd(DTPA-BDMA)] is a non-ionic paramagnetic
      complex designed for use as an extracellular magnetic resonance imaging (MRI)
      contrast agent. The R1 relaxivity value of [Gd(DTPA-BDMA)] is 4.13 +/- 0.2 mM-1S
      1, which is similar to that of [Gd(DTPA)]2- (4.08 mM-1S-1). The purpose of this
      study is to examine the acute toxicity and MRI characteristics of [Gd(DTPA
      BDMA)]. Our results show that the lethal dose (LD50) of the [Gd (DTPA-BDMA)] is
      10.58 mmol/kg in ICR mice, which is higher than that of [Gd (DTPA)]-2-(6.40
      mmol/kg). The MR images demonstrate that the enhancing effect and renal clearance
      of [Gd(DTPA-BDMA)] are similar to that of [Gd(DTPA)]2- either in control group or
      CHA (Cheng hepatoma ascites) tumor model in Wistar rats (p > 0.05). These
      findings indicate that [(DTPA-BDMA)] has similar characteristics of [Gd(DTPA)]2-
      and has the potential of becoming a safe and reliable magnetopharmaceutical for
      the extracellular MRI contrast agent.

PMID- 12056173
TI  - Analysis of factors associated with successful cardiopulmonary resuscitation in
      non-traumatic dead-on-arrival patients in emergency department.
AB  - Out-of-hospital cardiopulmonary arrest has a dismal prognosis. Successful
      resuscitation of these patients depends on the "chain of survival". In Taiwan,
      the emergency medical services (EMS) system is under development and the links of
      "chain of survival" are weak and frequently broken. A 2-year retrospective study
      was conducted from January, 1999, to December, 2000 to evaluate the factors of
      successful cardiopulmonary resuscitation (CPR) in non-traumatic DOA patients in
      ED. Of 175 studied patients, 51 patients (29.1%) were successfully resuscitated
      with return of spontaneous circulation (ROSC), but only 7 patients (4%) survived
      to hospital discharge. Most successfully resuscitated patients (84.3%) regained
      their vital signs within 30 minutes. There were no significant differences in
      age, sex, vehicle of transportation, administration of prehospital CPR or not,
      EMS response interval, on-scene duration, and scene-to-hospital interval between
      patients with ROSC and without ROSC. Compared with asystole cardiac rhythm,
      patients with pulseless electrical activity (PEA) had a higher successful
      resuscitation rate (p = 0.001), but no significant differences existed between
      patients with ventricular fibrillation/ventricular tachycardia (VF/VT) and PEA or
      VF/VT and asystole. However, there were no significant differences in the
      survival discharge rate among patients with different initial cardiac rhythms in
      ED.

PMID- 12056174
TI  - Isolated congenital ventricular septal aneurysm in an adult--a case report.
AB  - Congenital ventricular septal aneurysm without ventricular septal defect is a
      very rare condition. We describe the clinical features of an adult case and the
      literature was reviewed. A 54-year-old woman experienced intermittent palpitation
      with rapid heart beating sensation for several years. The duration was only
      several seconds. There was neither congestive heart failure nor syncope history.
      Physical examination revealed mid-systolic click with grade II/VI systolic murmur
      at apical area. Echocardiography disclosed mitral valve prolapse with mild mitral
      regurgitation. A ventricular septal aneurysm bulging into right ventricle was
      found incidentally. Transesophageal echocardiographic and cardiac angiographic
      pictures of ventricular septal aneurysm were demonstrated. Since the patient was
      relatively asymptomatic, no surgical intervention was advised.

PMID- 12056175
TI  - Bilateral traumatic testicular dislocation--a case report.
AB  - Traumatic testicular dislocation is a rare complication of blunt scrotal trauma.
      It is usually related to straddle injuries from motorcycle accidents and is
      commonly accompanied by scrotal hematoma and pelvic fracture. Bilateral
      dislocation of the testes is relatively rare. We report a rare case of bilateral
      testicular dislocation after a motorcycle accident. Abdominal computed tomography
      (CT) and color Doppler ultrasonography are helpful in locating the dislocated
      testicle and detecting its blood flow. Closed reduction of a superficial
      testicular dislocation may be attempted first. After appropriate physical
      examination and image study, emergent surgical reduction should be considered
      because of the high incidence of failure of closed reduction. We recommend that
      emergency physicians should be aware of potential testicular injury among trauma
      cases. Early reduction and early urological consultation are also recommended
      because of histological changes seen in dislocated testis.

PMID- 12056176
TI  - A rare and lethal complication of external collecting device for neuropathic
      voiding dysfunction--a case report.
AB  - We present a rare and severe complication of condom. A 78-year-old man of
      dementia and neuropathic voiding dysfunction were sent to our Emergency Room due
      to loss of consciousness. Preliminary examinations showed only tachycardia and
      hypotension that revealed a condition of septic shock. The abnormal laboratory
      examinations revealed leukocytosis and deteriorated liver and renal function.
      Urinalysis was unable to be collected at emergency room because it was difficult
      to indwell the Foley catheter. The penis looked more than twice normal length.
      Strong parenteral antibiotics were given after blood culturing with removal of
      the condom. After debridement, the catheterization was successful. The
      circumcised wound healed gradually post-operation. However, he died 5 days later
      because of his severe urosepsis.

PMID- 12056177
TI  - Relation between fat distributions and several plasma adipocytokines after
      exercise training in premenopausal and postmenopausal women.
AB  - Circulating concentrations of adipocytokines, such as leptin, tumor necrosis
      factor-alpha (TNF-alpha), and plasminogen activator inhibitor-1 (PAI-1), vary
      with exercise training, menopause, or regional variations in adipose tissues. In
      the present study, the relationships between body fat distributions and some
      adipocytokines were compared in premenopausal (N = 9) and postmenopausal women (N
      = 9), before and after exercise training. The training for 10 weeks (that is, 3
      days/week) consisted of aqua exercise plus resistance exercise. The training
      reduced percent fat, body mass index, total fat mass (TFM), subcutaneous fat mass
      (SFM), and plasma levels of leptin and PAI-1 in both women. Mean value of plasma
      TNF-alpha tended to increase after training in both women. Plasma leptin levels
      were lower in postmenopausal than in premenopausal women, independently of
      training. In premenopausal women, plasma leptin levels correlated well with
      either TFM or SFM before and after training. Regression analysis of decreases in
      plasma leptin with a reduced amount of SFM revealed that decreases in plasma
      leptin depended to a greater extent on a loss of SFM. In postmenopausal women, no
      significant correlation was found between leptin levels and any of the fat
      depots. Plasma TNF-alpha levels correlated well with visceral fat mass (VFM) in
      premenopausal but not in postmenopausal women. Changes in TNF-alpha levels after
      training correlated well with reduced amount of VFM in premenopausal but not in
      postmenopausal women. Plasma PAI-1 levels were not different between groups.
      Moreover, no significant correlation was found between PAI-1 levels and any of
      the fat depots in both women. Thus, in premenopausal but not in postmenopausal
      women, changes in plasma concentrations of leptin and TNF-alpha correlate well
      with specific alterations in relative amount of SFM and VFM after training,
      respectively. However, no significant relationship between PAI-1 and any of the
      fat depots was found independently of either menopause or training.

PMID- 12056178
TI  - An epidemiological study on relationship between the hours of sleep and life
      style factors in Japanese factory workers.
AB  - To prevent "life style-related diseases", it is necessary to evaluate not only
      the factors directly related to sleep but also the relationship between sleep and
      other life style-related factors (such as smoking, alcohol drinking, food habits,
      and exercise routines). There have been no extensive studies conducted on these
      relationships. A survey was conducted on 2,000 employees of a large plant over a
      6-year period to provide data that would allow one to analyze correlation between
      hours of sleep and other life style factors, such as smoking, alcohol drinking,
      dietary habit, and exercise. It focused on a serial evaluation, with special
      reference to the correlation between sleep and smoking and drinking habits,
      exercise, and food habits. In relation to smoking or an alcohol drinking habit,
      no significant correlation was found between those who did not get enough sleep
      and those who got adequate sleep. For the dietary habits, the group with
      insufficient hours of sleep was related to a less than satisfactory frequency of
      meal taking, irregularity of eating, snacking habits, excessive seasoning of
      food, and consumption of insufficient quantities of vegetables. Conversely, it
      was recognized that those who have satisfactory food habits are more likely to
      enjoy an appropriate amount of sleep. Those who fail to get sufficient sleep
      engage in food habits that are more likely to cause life style-related diseases.

PMID- 12056179
TI  - Cardiorespiratory capacity of Thai workers in different age and job categories.
AB  - The objective of this study was to assess the cardiorespiratory capacity of Thai
      male and female blue-collar workers in different age and occupational categories.
      The maximal oxygen uptake (VO2max) of 70 men and 56 women was assessed using a
      submaximal bicycle-ergometer test supplemented with ventilatory gas analyses. The
      age of the subjects varied from 16 to 55 years. They worked in construction,
      manual materials handling and metal jobs. For the male subjects the VO2 max
      ranged from 1.43 to 3.50 l/min and from 21.3 to 66.3 ml/min/kg. The corresponding
      values for the female subjects were 0.97-2.97 l/min and 16.2-42.4 ml/min/kg.
      According to the European fitness classifications the mean age related VO2max of
      the male and female subjects can be considered moderate or poor. When compared to
      the European data heart rate of the subjects was 25-30% higher at submaximal
      levels of oxygen uptake, confirming earlier results. The low cardiorespiratory
      capacity of many Thai workers may be a limiting or even risk factor in physically
      demanding jobs.

PMID- 12056181
TI  - The influence of light on circarhythms in humans.
AB  - The present review discusses two types of biological rhythms, namely, circadian
      rhythms and circannual rhythms. Humans possess a circadian rhythm of
      approximately 24 hours, which is regulated by neural and hormonal processes. The
      synchronisation of this rhythm with the solar day and night is maintained through
      entrainment mainly by light. Dark environments completely lacking windows may
      have a negative effect on well-being and work capacity. During shift work the
      biological clock tends to maintain its normal 'diurnal' rhythm, which may lead to
      extreme tiredness and increased risk of accidents. Negative effects such as these
      may be partially alleviated by means of bright light during the night. During air
      travel across several time zones there is little time for the biological clock to
      adjust, but the resulting 'jet lag' may possibly be overcome by means of
      appropriately timed exposure to bright light. In countries situated far from the
      equator, the biological clock may become seriously disrupted during the short
      days of the dark season. Characterised by fatigue, sadness and sleep problems,
      these seasonal affective disorders may be cured or alleviated by means of regular
      periods outdoors, better lighting indoors, or, in the most serious cases, light
      therapy.

PMID- 12056180
TI  - Relationship between muscle buffering capacity and fiber type during anaerobic
      exercise in human.

PMID- 12056182
TI  - Rehydration after exercise with fresh young coconut water, carbohydrate
      electrolyte beverage and plain water.
AB  - This is to cross-over study to assess the effectiveness of fresh young coconut
      water (CW), and carbohydrate-electrolyte beverage (CEB) compared with plain water
      (PW) for whole body rehydration and blood volume (BV) restoration during a 2 h
      rehydration period following exercise-induced dehydration. Eight healthy male
      volunteers (mean age and VO2max of 22.4 +/- 3.3 years and 45.8 +/- 1.5 ml min kg
      1 respectively) exercised at 60% of VO2max in the heat (31.1 +/- 0.03 degrees C,
      51.4 +/- 0.1% rh) until 2.78 +/- 0.06% (1.6 +/- 0.1 kg) of their body weight (BW)
      was lost. After exercise, the subjects sat for 2 h in a thermoneutral environment
      (22.5 +/- 0.1 degrees C; 67.0 +/- 1.0% rh) and drank a volume of PW, CW and CEB
      on different occasions representing 120% of the fluid loss. A blood and urine
      sample, and the body weight of each subject was taken before and after exercise
      and at 30 min intervals throughout a rehydration period. Each subject remained
      fasted throughout rehydration. Each fluid was consumed in three portions in
      separate trials representing 50% (781 +/- 47 ml), 40% (625 +/- 33 ml) and 30%
      (469 +/- 28 ml) of the 120% fluid loss at 0, 30 and 60 min of the 2 h rehydration
      period, respectively. The drinks given were randomised. In all the trials the
      subjects were somewhat hypohydrated (range 0.08-0.18 kg BW below euhydrated BW; p
      > 0.05) after a 2 h rehydration period since additional water and BW were lost as
      a result of urine formation, respiration, sweat and metabolism. The percent of
      body weight loss that was regained (used as index of percent rehydration) during
      CW, PW, and CEB trials was 75 +/- 5%, 73 +/- 5% and 80 +/- 4% respectively, but
      was not statistically different between trials. The rehydration index, which
      provided an indication of how much of what was actually ingested was used for
      body weight restoration, was again not different statistically between trials
      (1.56 +/- 0.14, 1.36 +/- 0.13 and 1.71 +/- 0.21 for CW, CEB and PW respectively).
      Although BV restoration was better with CW, it was not statistically different
      from CEB and PW. Cumulative urine output was similar in all trials. There were no
      difference at any time in serum Na+ and Cl-, serum osmolality, and net fluid
      balance between the three trials. Urine osmolality decreased after 1 h during the
      rehydration period and it was lowest in the PW trial. Plasma glucose
      concentrations were significantly higher compared with PW ingestion when CW and
      CEB were ingested during the rehydration period. CW was significantly sweeter,
      caused less nausea, fullness and no stomach upset and was also easier to consume
      in a larger amount compared with CEB and PW ingestion. In conclusion, ingestion
      of fresh young coconut water, a natural refreshing beverage, could be used for
      whole body rehydration after exercise.

PMID- 12056183
TI  - Two intent statements revised for hospitals.

PMID- 12056184
TI  - Revisions to emergency management standards approved for long-term care.

PMID- 12056185
TI  - How emergency management preparation fits in the survey process.

PMID- 12056186
TI  - Integrating physicians into the root cause analysis process.

PMID- 12056187
TI  - Long-term recovery from large-scale emergencies.

PMID- 12056188
TI  - Point of no return.

PMID- 12056190
TI  - Child supporter.

PMID- 12056189
TI  - Put a stop to stroke.

PMID- 12056191
TI  - The whole thing.

PMID- 12056192
TI  - In your own words.

PMID- 12056194
TI  - People with dyslexia are quite capable of nursing.

PMID- 12056193
TI  - Eating for health.

PMID- 12056195
TI  - Pre-operative fasting.
AB  - AIM: To investigate the nursing practice of fasting patients before surgery.
      METHOD: A descriptive research design was used. The instrument used was a
      structured interview schedule based on that of Hung (1992). A random sample of 20
      nurses was selected for the study. RESULTS: The findings indicated that patients
      fast for longer periods than research suggests is necessary. The communication
      between the operating theatre and the wards was found to be reasonably good in
      relation to notification about delays or alterations in the operating lists.
      However, half of the respondents did not give patients anything to eat or drink
      if a delay occurred. CONCLUSION: Ritualistic practice prevailed and there was a
      lack of application of research findings. There was general agreement about the
      need for change, but resistance to change was a major problem. This study has
      implications for nursing practice, education and administration.

PMID- 12056196
TI  - The need to combat clinical fraud.
AB  - This article explores the possibility that clinical fraud is being perpetrated on
      a daily basis at the interface between patient, nurse and others. This type of
      fraud might take place when nurses carry out, or fail to carry out, a clinical
      activity, in the way that they report the care delivered, or in the way that they
      conduct their relationships with colleagues. If any deception occurs before,
      during or following such activities then the nurse is guilty of fraud. If such
      fraudulent practice exists it could have negative consequences for patients and
      healthcare professionals. The authors examine the possible reasons for fraudulent
      practice.

PMID- 12056197
TI  - Assessment and management of hand and wrist fractures.
AB  - Injuries to the hand and wrist are common, and incorrect diagnosis and management
      can have catastrophic consequences for patients. This article discusses the
      causes, assessment, treatment and psychosocial needs of patients with hand or
      wrist fractures.

PMID- 12056198
TI  - Nurse challenges survey's hospital infection figures.

PMID- 12056199
TI  - Don't let 'leakage' sink your capitation contracts.

PMID- 12056200
TI  - Capitation not dead in California, but only the strong survive.
AB  - Capitation in California appears on the upswing two years after several large
      physician practice management companies and smaller medical groups went out of
      business.

PMID- 12056201
TI  - 'Benefits cycle' replacing premium cycle as consumerism takes hold.
AB  - The traditional premium cycle of ups and downs in rates is giving way to a new
      phenomenon--driven by the advent of consumerism in health care--termed the
      "benefits cycle" by one consultant. Rather than shifts in rates, he argues, the
      future will see shifts in benefits packages.

PMID- 12056202
TI  - Benchmarks reveal inpatient indicators, reimbursement trends.
AB  - Data from InterStudy confirm that HMO enrollment in metropolitan markets
      continues to decline even as inpatient utilization inches upward. The collision
      of these trends may portend challenges down the road for capitated providers.

PMID- 12056203
TI  - New options may improve accuracy of risk adjustment.
AB  - While the ability to risk-adjust payments is increasingly important to provider
      groups and health plans, diagnosis data that have been found to be the best
      predictors often are not readily available. But help may be on the way in the
      form of predictive programs that use either pharmacy data alone or pharmacy data
      in combination with inpatient data.

PMID- 12056204
TI  - CMS trying to boost fairness of cap payments in Medicare+Choice.
AB  - The Centers for Medicare and Medicaid Services (CMS) is hoping that its new model
      for risk adjustment under the Medicare+Choice program will make for a fairer
      payment system.

PMID- 12056205
TI  - Troubleshooting the Herbst appliance.

PMID- 12056206
TI  - Addition of uprighting and rotating springs to standard edgewise or preadjusted
      brackets.

PMID- 12056207
TI  - How does your orthodontic practice stack up?

PMID- 12056208
TI  - Molar control. Part 5.

PMID- 12056209
TI  - Delayed development of a maxillary left second premolar.

PMID- 12056210
TI  - Simplified multistranded retainers.

PMID- 12056211
TI  - Clinical application of micro-implant anchorage.

PMID- 12056212
TI  - Testing your diagnostic skills (#61). Case 1. Periodontal abscess, lateral
      periodontal cyst and odontogenic keratocyst.

PMID- 12056213
TI  - Testing your diagnostic skills (#61). Case 2. Pemphigus vulgaris.

PMID- 12056215
TI  - Needle-exchange programs are slowly finding greater acceptance.

PMID- 12056214
TI  - Member disagrees with specialty-advertising editorial.

PMID- 12056216
TI  - ADAP report offers sobering view of programs.

PMID- 12056217
TI  - Multistage pooling finds acute and early infection.

PMID- 12056218
TI  - Vaccine trial participants may show false positives.

PMID- 12056219
TI  - Drug-resistant virus tracked through 3 men.

PMID- 12056220
TI  - New rapid HIV tests fare well in study.

PMID- 12056222
TI  - General Assembly deals with CareFirst conversion.

PMID- 12056221
TI  - Managed care: the year in review.

PMID- 12056223
TI  - One legislator's viewpoint of the BPQA "sunset review".
AB  - You can see that legislation can be affected at many levels, and advocacy can
      play a crucial role in the outcome. Next year, I hope that I will be able to
      write the conclusion of the BPQA sunset legislation story. In the meantime,
      please continue to advocate for physicians and our patients in Maryland. Our
      legislators need to hear from people like you who really understand how health
      care is being delivered in Maryland.

PMID- 12056224
TI  - Maryland physicians win $50 million in additional funding for reimbursement.

PMID- 12056225
TI  - A review of Maryland insurance law.

PMID- 12056226
TI  - Read all about it.

PMID- 12056227
TI  - Art, artists, and arthritis.

PMID- 12056228
TI  - Durability of vaccinia immunization based on reaction at the rechallenge site.
AB  - The authors reviewed the immunization records of 621 patients who received
      vaccinia vaccination in our Occupational Medicine Clinic between July 26, 1994
      and October 11, 2001 to evaluate the durability of the vaccine over time, as
      judged by the patients' local skin reactions following revaccination. Results of
      the study document a waning immunity to vaccinia immunization in the majority of
      re-vaccinees. Over 63.4 percent of those previously immunized in the study
      population were found to lack adequate immunity against vaccinia rechallenge
      based on their response to it. Of the remaining third, only 6.4 percent elicited
      an immune response to rechallenge. Overall, 75.5 percent of those receiving
      vaccinia vaccination in the clinic lacked adequate immunity. Given that this
      study involved a young, healthy, HIV-negative, pre-screened workforce, the actual
      projected immunity to vaccinia of the general population should have been
      significantly lower. Although the study data suggests the persistence of adequate
      immunogenicity of the vaccinia vaccine stockpile, over the past year an increased
      frequency (3.7 percent) of vaccine-associated cellulitis was noted, coinciding
      with the Centers for Disease Control (CDC) decision to allow vaccinia vaccine
      stockpile to be used after its expiration date of April 2000.

PMID- 12056229
TI  - The need for medical evidence when using herbs.

PMID- 12056230
TI  - Reading the research literature. Putting randomized clinical trials into
      practice. 2.
AB  - Randomized clinical trials (RCT) are our best available method for determining
      whether a treatment works or has what we technically call efficacy. RCTs set out
      to demonstrate that a particular treatment regimen works better than a
      conventional standard treatment or placebo, for a particular type of patient,
      with a particular condition or indication. The results of an RCT are, generally,
      used by the Food and Drug Administration (FDA) as the basis for approving
      treatments--especially drug treatments. The approval of a drug generally
      indicates that at least two independently conducted, randomized clinical trials
      have demonstrated that the treatment has efficacy for at least one indication.
      Once a drug is FDA approved, a physician has the authority to prescribe it for
      the approved, as well as other, indications. However, if used for another
      indication, a physician may risk a greater liability, should the outcome not be
      as expected. Unfortunately, RCT conducted for one indication cannot be used to
      support either the efficacy or safety of the treatment for another indication.
      Even when used for an approved indication, it is difficult to know what to expect
      when a new treatment is put into practice. The most difficult part of reading
      medical literature is to apply or put it into practice--what we call
      extrapolation. Extrapolation differs from interpretation, which refers to results
      of patients included in the investigations, while extrapolation asks questions
      about those who receive the treatment in practice. This important distinction is
      called effectiveness--when a treatment works in practice, as opposed to efficacy,
      which indicates it works under the conditions of an RCT. Authors of a randomized
      clinical trial draw conclusions about effectiveness as well as efficacy, because
      they are eager to have their successful treatment used and, despite being
      tempered by the peer review process, are likely to encourage its widespread
      adoption. Even if the author is not biased toward adopting the treatment, it is
      important to recognize that you, as the practitioner, know your patients best.
      Your patients may be quite different from those included in the RCT. Therefore,
      we need a systematic approach in order to draw conclusions from an RCT and apply
      them in practice. This paper will take a look at two basic questions in order to
      apply the results of an RCT. It will ask how large an impact can we expect on
      average for patients who are different from those in the RCT, and what
      conclusions can we draw about safety from an RCT?

PMID- 12056232
TI  - Alternative views essential.

PMID- 12056233
TI  - Preventing medical errors a priority.

PMID- 12056231
TI  - Comparing NHANES data in the assessment of hypertension of African-Americans.
      Awareness, treatment and control of hypertension in an urban Maryland city.
AB  - Although hypertension is a well-recognized risk factor for stroke, heart failure,
      and renal failure, particularly among African-Americans, many with high blood
      pressure are unaware of its presence. Those who are cognizant of their high blood
      pressure are often not treated at appropriate levels, as recommended by the Joint
      National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure (JNC VI). In 1999, we participated in a blood pressure screening
      at the Wicomico County, Maryland Health Fair, whose primary focus was the Health
      and Wellness of African-Americans. Wicomico County is located on the Eastern
      Shore of Maryland. Our participation in the health fair screening of a
      predominantly African-American population afforded us the opportunity to update
      data from the National Health and Nutrition Examination Survey (NHANES) and
      determine if JNC VI guidelines were being met, especially among the diabetic
      population. Since the NHANES data is now over five years old, we felt that our
      study would be of interest to physicians working with patients who have
      hypertension. Our findings compared to the NHANES II last published in 1994. We
      were looking for any improvement in the detection and treatment of hypertension.
      Data analysis found a slight increase in the awareness and treatment of
      hypertensives, but a decrease in the number of patients who were able to manage
      their illness. This was particularly true among diabetics who were at high risk
      for hypertension.

PMID- 12056234
TI  - CareFirst Blue Cross Blue Shield of Maryland denies psychotherapy services to
      individuals with AD/HD.

PMID- 12056235
TI  - Evaluations of clinical learning in a managed care environment.
AB  - TOPIC: Clinical learning in a managed-care environment. PURPOSE: To obtain
      evaluative data about clinical learning experiences for graduate nursing students
      based on the domains of competence for successful practice in managed-care
      organizations. METHODS: A survey of 42 nurses (20 graduate students, 22 nurse
      practitioner preceptors) self-reported on two questionnaires. FINDINGS: Both the
      students and preceptors reported that there were learning opportunities for
      research utilization, the development of clinical competence, the identification
      of group dynamics, the development of leadership skills. In addition, the
      respondents reported learning opportunities to examine the financial impact on
      healthcare delivery and clinician decision making. The area of ethics and its
      impact on clinical decision making is an apparent void, as reported by the
      respondents. CONCLUSIONS: A managed care environment does provide an effective
      learning environment for nurse practitioner students.

PMID- 12056236
TI  - Said another way. The place of baccalaureate nursing programs in the liberal arts
      setting.

PMID- 12056237
TI  - Touchy-feely or hard-core medicine: let the patient be the judge.

PMID- 12056238
TI  - Invest in yourself. Start a clinical research project.
AB  - Experienced clinical healthcare providers ought to investigate challenging roles
      and activities. The utilization of seasoned role models is an effective method
      for learning thought-provoking aspects of the professional role. Lifelong
      learning is a responsibility for every professional nurse. The challenge of
      seeking and succeeding at acquiring new competence within a different role is a
      goal to be aggressively sought in the current healthcare arena. The willingness
      to confront fears and challenges is a quality to be developed and utilized. As
      the nursing profession is endeavoring to establish its unique place in the
      healthcare field, the eagerness to confront challenges is a quality to be valued.
      Since the face of America is changing, professional nurses must be ready and
      capable of meeting the challenges confronting the healthcare arena. Cultural
      awareness, moving to a higher level of practice by incorporating research ideas,
      and changing the mindset of how nurses think are vital aspects integrated into
      this changing environment. Nurses must have a vision about the future. By being
      open and interested in seeking new trials, the nursing profession can make
      changes to improve the future for clients, thus the practice of nursing.

PMID- 12056239
TI  - The health-care nightmare: when will we awaken?

PMID- 12056240
TI  - Behavioral maintenance: a closer look.
AB  - TOPIC: Behavior maintenance. PURPOSE: To discover the descriptive picture of how
      an individual with type 2 diabetes self-managed and adapted the necessary
      behavior changes into her daily lifestyle. SOURCES: Personal research and
      literature review. CONCLUSION: Behavioral maintenance to self-manage a specific
      regimen for people with type 2 diabetes is complex and difficult. It is important
      for nurses "not to jump to conclusions" and assume the client has not made the
      necessary changes to incorporate the behavior changes into a life style routine.
      Nurses need to be cognizant of the differences and unique situations of their
      clients when teaching them about managing their disease.

PMID- 12056241
TI  - Considerations and suggestions on a new treatment for Barre-Lieou syndrome.

PMID- 12056243
TI  - Peritalar release in the treatment of congenital talipes equinovarus clubfoot.
AB  - It is the purpose of this retrospective study to evaluate the results of the
      surgical treatment of congenital talipes equinovarus clubfoot. Seven patients
      affected with congenital talipes equinovarus clubfoot, 2 of which bilateral,
      treated surgically using peritalar release according to Simons were re-examined.
      The long-term follow-up results obtained after an average of 4 years were
      evaluated from clinical, morphofunctional, and radiographic points of view, and
      with the help of a photopodogram and computed baropodometry. The subjective
      satisfaction of the patients was also evaluated. Results were considered to be
      good in all of the cases. In conclusion, surgery involving peritalar release
      allows for correction of abduction of the forefoot, and restores physiological
      calcaneal valgus, re-balancing standing on the plantar surface; the persistence
      of an area of hypostanding in the forefoot operated on and of mild, residual
      cavus of the plantar arch do not, thus, seem to influence the good results
      obtained.

PMID- 12056242
TI  - Adjuvant and neoadjuvant chemotherapy in osteosarcoma.
AB  - Associated chemotherapy (adjuvant or neoadjuvant) means the association of
      systemic pharmacological therapy to local therapy in the treatment of tumors
      that, although appearing to still be localized at the time of diagnosis, have a
      high probability of having already given systemic micrometastases. The purpose of
      this kind of treatment is that of controlling the micrometastases present, even
      if they can't be documented, in many tumors. These neoplasms, although still
      apparently localized, do not achieve healing with the simple removal of the
      primary tumor, precisely because of the presence of these micrometastases. The
      current treatment of osteosarcoma (OS) commonly makes use of these therapies.
      There are different types of OS and they are not indicated in all associated
      therapies, nor do they provide the same results. We may begin by distinguishing
      between "high-grade" forms, which have a considerable tendency to early
      metastasis (about 96% of cases) and "low-grade" forms, generally characterized by
      local malignancy alone (about 4% of cases). Based on the site on which they
      occur, OS may be "primary," that is, occurring on apparently normal bone (about
      95% of cases) and "secondary," that instead occur on bone that is in some way
      already changed (as a result of radiation, infarction, Paget's disease, etc.).
      Based on the site and on the staging, OS can be subdivided into forms of the
      limbs (75% of cases) and "forms of the axile skeleton" (25% of cases) and in
      forms that are "still localized" at the time of diagnosis (80% of cases) and in
      forms "with metastases that are documented at the onset (20% of cases). The
      present review only concerns primary high-grade OS of the limbs that were not
      metastatic on diagnosis, representing about 60% of all OS, and it is based on the
      experience of the Rizzoli Orthopaedic Institute where, between 1983 and 1996, a
      total of 731 patients were treated by neoadjuvant chemotherapy using five
      different protocols that were subsequently activated (Table I).

PMID- 12056244
TI  - Our results in the treatment of fractures dislocations of Lisfranc's joint.
AB  - The authors report their experience in the treatment of traumatic injuries of
      Lisfranc's joint based on 30 cases treated by surgery between 1984 and 1999. All
      of the patients were re-evaluated clinically and radiographically. What emerges
      from the study is the need for surgical stabilization with percutaneous Kirschner
      wires or by open procedure in cases where there are doubts or where reduction is
      impossible. The prognosis is worse in injuries of the medial column and in
      exposed fractures or when mortification of the soft tissues is present.

PMID- 12056245
TI  - The current and effective use of the dynamic axial fixator in the treatment of
      exposed fractures of the leg.
AB  - The authors observed rapid, practical, effective, and excellent tolerance in the
      use of the Orthofix dynamic axial fixator in the treatment of leg fractures.
      Good, stable reduction performed in an emergency situation, with respect for
      tissues that had been exposed to trauma, with fragments in compression when
      possible, and correct postsurgical management using early dynamization, are the
      goals to be attained for the physiological development of the bone callus.

PMID- 12056246
TI  - Experimental study on rotator cuff repair.
AB  - It was the purpose of the experimental study to use laboratory experience to
      verify the effectiveness of different methods used to repair the rotator cuff.
      The sheep was used as an animal model because its infraspinous tendon is the most
      similar to that in the human. Three static trials were conducted using Instron
      machines, comparing the repair systems used most by the same authors in their
      clinical work, the hold of the suturing wires with two different threading
      procedures in the bone tunnels and two types of knotting, and the breakage
      loading of the suturing wires in the two different miniplate systems. The authors
      conclude that tendinous anchoring must be entrusted to reinforced suturing
      systems (modified SCOI and Mason Allen), the threading of wires in pairs in a
      single bone tunnel makes surgery easier and shortens the amount of time required,
      with threading of wires similar to or better than threading with a single wire.
      There are no differences in breakage loading of the wire at the level of the
      holes in the two miniplates considered in this study.

PMID- 12056247
TI  - Glenoid hypoplasia. Description of a clinical case and analysis of the
      literature.
AB  - Glenoid hypoplasia, or dysplasia of the scapular neck, is a relatively rare
      alteration that in most cases involves the pectoral girdle in a bilateral and
      symmetrical manner. In general, glenoid hypoplasia is associated with skeletal
      changes such as hypoplasia of the humeral head, or changes in the morphology of
      the acromion and of the coracoid. The authors describe a case of unilateral
      glenoid hypoplasia, which was symptomatic for a few years, reporting the clinical
      radiographic findings and based on the data published in the literature reporting
      how this disease, which often goes unrecognized, is much more frequent than is
      imagined.

PMID- 12056248
TI  - Osteoid osteoma of the lumbar spine. A case report.
AB  - The authors report the case of a patient aged 10 years with late diagnosis of
      osteoid osteoma localized in the right pedicle of L1 due to a paucisymptomatic
      and aspecific clinical onset, characterized only by the occurrence of left-convex
      wide-range scoliosis that was completely solved after surgical excision of the
      neoformation.

PMID- 12056249
TI  - The diagnosis and treatment of an atypical case of acetabular fracture in a
      patient with bilateral coxa vara.

PMID- 12056250
TI  - [T.V.T.: a new operation to correct stress urinary incontinence].
AB  - The author presents a video with a new surgical technique to correct the urine
      effort incontinence in women, known as T.V.T. (tension-free vaginal type), it
      means, free tension band. It is called so because raising the vesical neck, it
      doesn't knot neither fixes to any structure. It is a simple technique, that can
      be make as major ambulatory surgery, and in our experience over one hundred
      cases, it solves finally the effort incontinence, and it improves appreciably the
      neutrogen component in mixed incontinences.

PMID- 12056251
TI  - [Past and present of branchial arches].
AB  - The author effects a descriptive analysis of the different glandular thyroid
      stage, especially of side sketches, that taking as a basis our observations, we
      consider and demonstrate that they are originated only starting from the fourth
      bursae, because the parathyroids glands are ectodermic deriiated proceeding from
      the epicardic branchial placode, situated on the dorsal surfaces of the fourth
      epic blastic sulcus, both approaches opposite to classically accepted.

PMID- 12056252
TI  - [Current problems of cesarean section].
AB  - With the diminution of maternal and perinatal mortality, the Cesarean sections
      rates has increased in the world, and has produced preoccupation and restlessness
      in health providers and scientists. This increase of the Cesarean sections rates
      has been due to multiple reasons. These reasons are the increasing fetal
      interest, the different conception and its processing, in which it influences a
      lot the present preparation of obstetricians, the valuation of the fetal well
      bearing, the obstetrical attitude in breech presentations and iterative cesarean
      sections, and of course, the social and economic pressures that carry the fear to
      the judicial claims, which are increasing in all developed countries. The aim of
      this this article is to analyze the ways to decrease this cesarean sections
      rates, analyzing causes of the increase, treating to describe obstetrical
      protocols to achieve an ideal number of cesarean sections.

PMID- 12056253
TI  - [Somatoform depressive disorders].
AB  - The Tetra-dimensional Model of Depression has several advantages for diagnosis
      and therapy in relation to other models. Therefore, somatoform depressive
      symptoms are described here following this model. In the depressive mood, pain
      and paraesthesiae are the most important somatic symptoms. In the anergy, chronic
      fatigue, irritable bowel and sexual inhibition. In the communication disorder,
      vertigo and limitation of facial expressivity. In the rhytmopathy, insomnia and
      bulimia. In order to detect the depression in a clinical picture integrated by
      functional somatic symptoms we haven seven kinds of features: personal and family
      history, clinic and evolutive aspects of somatic symptoms, the search of psychic
      symptoms, the therapeutic reaction and the type of the personality.

PMID- 12056254
TI  - [A new history of basal ganglia and physiopathology of Parkinson's disease].
AB  - The author analyzes basic and clinical experimental works of the last forty years
      and reaches the following conclusions: The motor system is an indivisible entity
      in which the basal ganglia are a key part. An important link in the history of
      the basal ganglia is the description by Llamas and Reinoso-Suarez in 1965 of
      connections from the substantia nigra compacta to the globus pallidus medialis
      and lateralis, and striatum through extremely thin, diffusely distributed fibers.
      They also described connections from the ventral tegmental area to the basal
      forebrain and the cerebral cortex. These connections are still not accepted one
      decade later. Rather than as cortico-basal ganglia-cortical parallel loops, the
      basal ganglia are actually structured as a widely distributed neuronal network
      with a great biochemical and connective variety. Basal ganglia intrinsic circuits
      have an important influential role in this network. Very varied brain structures
      influence basal ganglia neuronal network, mainly the cerebral cortex and the
      thalamic nuclei, essentially those that receive output from the basal ganglia.
      This complex organization provides the foundations for and elucidates the
      difficulty of explaining the pathophysiology of the clinical manifestations of
      Parkinson's disease as well as illustrating the need for future multidisciplinary
      research on this topic.

PMID- 12056255
TI  - [Vascular and cerebral aging: prevention with GH].
AB  - Endocrine system hormonal secretion decreases during aging. The reduction of
      estrogens and GH exert a very important influence on cardiovascular and central
      nervous system functions, both systems being nowadays the most frequent
      responsible for illnesses and death in our society. To investigate the
      therapeutical effects of GH and estrogens on aging induced morphological and
      functional changes on vascular and cerebral tissues, young (5 months) and old (22
      months) rats were compared. Male and female animals were used; some of the female
      rats were castrated to study the role of estrogens. Old rats exhibited thicker
      arterial wall than young animals, but GH and estrogens treatment was able to
      recover young morphological aspect. Vasodilatory reactivity to Isoprenaline and
      acetilcholine was reduced in old rats as compared to young ones, recovering the
      function when treated both with GH or GH and estrogens. Vasoconstrictory response
      to angiotensin was more marked in old rats especially in the castrated females,
      but GH and estrogens treatment reverted this effect. At cerebral level
      concentration of glutamine, arginine and aspartate was diminished in old male
      rats in the hypothalamus, the diencephalon and the temporal area, recovering
      young values when treated with GH; increased values of citruline in old rats
      considerably decreased when treated with GH. GH treatment seems to exert a
      beneficial effect on vascular and cerebral functions in old rats.

PMID- 12056256
TI  - [The Gioconda from the historical and medical perspective (hypotheses of
      pathology in her painting)].
AB  - As a preamble, some historical and biographical brushtrokes of the Gioconda,
      Leonardo and his painting will be outlined. Following these observations, a
      series of medical interpretations will be put forth regarding his painting with
      the aim of analysing possible pathologies related to: the skin, hair, eyes, hands
      and the reproductive and endocrine systems. We will conclude by observing the
      famous work The Smile and by extracting a hypothesis on pathologies of various
      natures such as: neurological, muscular, hypoacusic, asthmatic, psychoneurotic,
      psychiatric, ethylic, sexual, stress-related, stomatological (bruxismo) and the
      driving force that lies behind setting off the Stendhal Syndrome: a psychosomatic
      disorder known to be due to the human being's susceptibility to saturation from
      having received impressions of great artistic beauty.

PMID- 12056259
TI  - [Quality control in parasitology].
AB  - Between 1990 and 1996 we coordinated a Quality Control (QC) Program in
      Parasitology directed to Public Health Institutions in Spain. Periodically,
      parasited specimens, mainly feces or blood, were sent to Microbiology
      Laboratories for identification. Each QC was accompanied by a short clinic and
      epidemiological information in order to help in the diagnostic approach. After
      the answers to the QC were received a bulletin that included the solution to the
      QC, comments on the several answers received and a chapter with parasitological
      themes related with the QC, was sent to each participating Laboratory. The
      bulletin was accompanied by a card that included a photograph and a short
      description of the organism object of the QC.

PMID- 12056258
TI  - [Genetics of autoimmune diseases].
AB  - The publication of the human genome sequence this year was an important milestone
      in Biology. Autoimmune diseases arise through a complex interaction of genetics
      and environmental factors. They are influenced by more than one gene and do not
      exhibit a simple mode of inheritance. Some of the involved genes are thought to
      play a role in several autoimmune diseases whereas others seem to be specific for
      one of them. We have studied mainly genes located on the Major Histocompatibility
      Complex situated on the short arm of the 6th chromosome. This region is the most
      important genetic determinant for autoimmune diseases. It carries many genes
      playing a role in immune response and several have been observed to be associated
      with autoimmune diseases susceptibility. Although what has been published is just
      a draft of the human genome sequence, and a lot of work is needed to make sense
      of all these data and move into the study of gene function, the important
      technology breakthroughs of the last few years in genomics, proteomics and
      bioinformatics will speedup the study and results may come much earlier than
      could be imagined some years ago.

PMID- 12056260
TI  - [Orfila and the organization of medical studies].

PMID- 12056261
TI  - [Carbuncle (anthrax) as biological weapon].
AB  - The authors explain the anthrax pathogeny as necessary base to treat the systemic
      anthrax, that it can be secondary to a terrorist aggression, that until now it
      causes death to damaged people. For fear that a contamination with anthracis
      spores by a terrorist aggression, it is imposed to administrate chymeprotection
      to damaged people, because once it is appeared the symptoms of the systemic
      illness, the antibiotics don't stop the process evolution. For that reason, we
      think it is important to know the process pathogeny, where it can be found the
      keys for effective treatment of carbuncle sepsis.

PMID- 12056262
TI  - [General features of biological war].
AB  - After a historical introduction, the author points out the situation on the
      Biological and Toxin Weapons Convention of 1972, the biological programmes and
      the power's attitudes. Biological agents characteristics are quoted, as well as
      the difficulties to convert them into weapons and its massive bioterrorist use.
      Likely agents are listed and protection techniques, or epidemiological fight, are
      explained according to the classical 3-link acting method: sources, environment,
      and susceptible. The author emphasizes the importance of intelligence and
      cooperation between military health and civil protection services.

PMID- 12056263
TI  - [Echinococcus multilocularis: the prevalence of the fox tapeworm with possible
      serious consequences for humans].
AB  - The prevalence of the fox tapeworm in foxes (final host) and muskrats (one of the
      intermediate hosts) in the Netherlands and Europe has been discussed. The
      tapeworm was found in 9.4% of the investigated foxes from the province of
      Groningen and in 0.2% of the muskrats from the same region. Also in the province
      of Limburg positive foxes were found, but no positive muskrats. Possible ways of
      infection for humans are described together with methods for prevention. It is
      concluded that at this moment risks for humans to become infected are minimal,
      but vigilance and monitoring of foxes and muskrats remains needed.

PMID- 12056264
TI  - [Biotechnology, especially genetic modification, and legislation].
AB  - Biotechnology and genetic modification (GM) related legislation is not yet fully
      developed in the European Union (EU). New legislation has been recently issued
      ('Introduction of GMO's in the environment') and recently proposals from the
      European Commission ('GMO's in food and feed' and 'Traceability and labelling of
      GMO's') entered the decision-making process in the end of 2001. The proposals for
      the establishment of the European Food Authority play a role in this respect. GMO
      legislation is complex not in the least because of the demands for the dossiers,
      to be submitted with an application, while these procedures for admission must
      become more transparent. In this paper the relevant legislation will be discussed
      with the exception of that related to human health. Because of dissatisfaction
      with the present legislation, the European Commission in the past years granted
      no new approvals for introductions on the market of GMO's and for GM novel foods.
      New legislation should suspend the present de-facto moratorium. The tasks and
      position of the Inspectorate for the Health Protection and Veterinary Public
      Health is discussed. A provision has been made in the legislation with respect to
      adventitious or technically unavoidable contamination of raw materials with GMO's
      up to a maximum of 1%, of which the enforcement is not yet watertight. The
      analytical methods are being still developed.

PMID- 12056265
TI  - [Predecessors: veterinarians from earlier times (47). James Beart Simonds (1810
      1904)].

PMID- 12056266
TI  - [The fab(ulous) four].

PMID- 12056267
TI  - [Veterinary assistant prefers Animal Day above wedding on February 2. "Also a cat
      can have enough of eating food'].

PMID- 12056268
TI  - [The consumer's right to information].

PMID- 12056269
TI  - [Controlling foot and mouth disease. 'Stamping out' or use scientific research?].

PMID- 12056270
TI  - [Symposium on prevention and epidemiology of parasitic diseases. Travemunde,
      March 2002].

PMID- 12056271
TI  - [Diabetes Mellitus in a Guinea Pig].

PMID- 12056272
TI  - [Vaccination or collaboration?].

PMID- 12056273
TI  - [Instrumentation and implant systems of the spine].

PMID- 12056274
TI  - [Neon--a new angle-stable implant system for dorsal occipitocervical
      instrumentation. Biomechanical comparison with established systems].
AB  - Posterior instrumentation of the occipitocervical spine is well-established for
      different indications. The aim of this study was to evaluate whether posterior
      internal fixation of the occipitocervical spine with the new implant system
      improves primary biomechanical stability. Primary stability was significantly
      increased in all load cases with the new modular implant system compared to the
      other implant systems. Pedicle screw instrumentation tended to be stabler
      compared to lateral mass screws; nevertheless, significant differences could be
      observed only for lateral bending. As the experimental design precluded any
      cyclic testing, the data represent only the primary stability of the implants. In
      summary, this study showed that posterior instrumentation of the cervical spine
      using the new neon occipito-cervical system improves primary biomechanical
      stability compared to the CerviFix system and the Olerud cervical rod spinal
      system.

PMID- 12056276
TI  - [MAC-TL twin screw. A new thoracoscopic implantable stabilization system for
      treatment of vertebral fractures--implant design, implantation technique and in
      vitro testing].
AB  - Due to the lack of an appropriate instrumentation system for minimally invasive
      procedures to treat spinal fracture, a new thoracoscopically implantable
      stabilization system was developed. This report describes the new implant design
      and implantation technique. In a biomechanical in vitro study, an anterior
      corpectomy model representing the worst case of burst fracture instability was
      simulated, and the primary stability parameters of the new system were evaluated
      in comparison to a dorsal stabilization system. With the interbody graft and
      fixation, the new system demonstrated higher stabilizing effects in
      flexion/extension and lateral bending and restored axial stability beyond the
      intact spine and the dorsal stabilization system. Considering all the advantages
      of the endoscopic procedure and this biomechanical characterization, the clinical
      trial is warranted; its usefulness has been demonstrated in more than 150 cases
      in a multicenter study to date.

PMID- 12056275
TI  - [Vertebral body stenting. A method for repositioning and augmenting vertebral
      compression fractures].
AB  - Purpose of the study was to demonstrate the effectiveness of expanding a
      fractured vertebral body by transpedicular dilatation and stenting. 7 human
      cadaveric vertebral bodies from L2 to L5 underwent axia compression until a
      vertebral burst fracture was provoked. Then, by bilateral transpedicular
      approach, balloon-catheters were introduced, which were armed with stents,
      usually used for angioplasty. The catheters were inflated with radiolucent fluid
      and the stents expanded under radiologic control. After expansion, the balloon
      was deflated and removed, the stents resting inside the vertebral body, holding
      their inflated shape. Then, the resulting hole was filled with an injectable
      biodegradable calcium-phosphate. CT-scans were performed after destruction and
      after expansion. Morphology before and after expansion was judged, using 3-D
      reconstructions. Vertebral body strength was measured before destruction and
      after treatment with an Instron testing machine. RESULTS: Vertebral body shape
      could be restored. Also impressed central parts of the bony endplate could be
      elevated by using a convergent approach through the pedicles. There was no
      collapse of the vertebral body after removing the catheter-balloons The vertebral
      body strength could be restored up to a physiologic level. This procedure gives
      new perspectives in the treatment either of osteoporotic compression or traumatic
      vertebral fracture. By using CT-guided technique, it could be performed by a
      minimally invasive approach percutaneously.

PMID- 12056277
TI  - [Placement of pedicle screws using different navigation systems. A laboratory
      trial with 12 spinal preparations].
AB  - A well-known problem occurring with thoracolumbar spondylodesis is the
      perforation of pedicle screws through the pedicle wall. It occurs in up to 40% of
      the implanted screws. To reduce this problem, computed tomography (CT)-based
      navigation systems have been introduced, which allow the surgeon multidimensional
      control of the screw position in virtual reality and real time during insertion.
      In the recent past, fluoroscopy-based navigation systems have also been built. We
      inserted 77 pedicle screws in human lumbar cadaveric spine specimens either
      without navigation, with CT-based navigation, or with fluoroscopy-based
      navigation. In the critical sizes of pedicles between 6.5 and 9 mm, we found the
      best results with CT-based navigation, but there was no significant difference
      between the three methods. The minimal pedicle and the screw diameters should be
      reported in every study on pedicle screw misplacement and spine navigation since
      they represent the most important factor in pedicle wall perforations.

PMID- 12056278
TI  - [Computer navigation in dorsal instrumentation of the cervical spine--an in vitro
      study].
AB  - Transarticular C1/2 screws are widely used in posterior cervical spine
      instrumentation. Pedicle screws in the cervical spine remain uncommon until now.
      In view of improved biomechanical stability compared to lateral mass screws,
      pedicle screws could be used, especially for patients with poor bone quality or
      defects in the anterior column. Nevertheless, there are potential risks of
      iatrogenic damage to the spinal cord, nerve roots, or the vertebral artery
      related to both techniques of posterior cervical spine instrumentation.
      Therefore, the aim of this study was to evaluate whether C1/2 transarticular
      screws as well as transpedicular screws in C3 and C4 can be applied safely and
      with high accuracy using a computer-assisted surgery (CAS) system. C1/2
      transarticular screws as well as transpedicular screws in the cervical spine can
      be applied safely and with high accuracy using a CAS system in vitro. Therefore,
      this technique may be used in the clinical setup due to improved accuracy and
      reduced radiation dose for the patient and medical staff. Nevertheless, to
      prevent iatrogenic damage, users should be aware of known sources of possible
      errors that cause inaccuracies. Small pedicles with a diameter below 4.0 mm may
      not be suitable for pedicle screws.

PMID- 12056279
TI  - [Sources of error and risks in CT based navigation].
AB  - Based on the experience of 4 cervical, 102 thoracic/lumbar pedicle screw and 14
      transiliosacral screw implantations all problems and complications were
      collected. Problems noted within the data collection in the preoperative CT were
      an incomplete acquisition of the surgical target (n = 3), an exceeding of the
      processable scan slices (n = 1) and a non focused field of view. Transmission of
      the CT datas often were documented as incomplete (n = 16). Segmentation of the CT
      dataset turned out to be the significant problem with incorrect differentiation
      of the bone-soft tissue transition (n = 2), where as the choice of the matching
      points and the trajectories did not provoke any mistakes in the planning modus.
      The intraoperative matching of both corresponding datasets was insufficient (n =
      7), while the assignment of the CT dataset to the correct vertebral was not a
      major problem (n = 1). Navigation was not possible (n = 2) due to an instability
      of the spinal process. All fiducial based matching procedures (pelvis) were
      carried out without any problems. During intraoperative navigation potential
      complications resulted from deformation of instruments (n = 1) and interaction of
      instruments and the data reference base (n = 2). Further, the CT-based navigation
      of fractured vertebrae or unstable iliosacral joints is not safe, because
      dislocations between acquisition of the dataset and operation will lead to
      misguidance.

PMID- 12056281
TI  - [Effective in vivo radiation dose with image reconstruction controlled pedicle
      instrumentation vs. CT-based navigation].
AB  - There is a rapid increase of computer-assisted surgery (CAS) in the spine for
      insertion of pedicle screws. In contrast to the traditional technique using
      fluoroscopy, CT is the primary source for surgical navigation systems. PURPOSE OF
      THE STUDY: To compare organ and effective doses of fluoroscopy-controlled versus
      computer-assisted pedicle screw insertion under the aspect of risk reduction and
      number needed to treat. MATERIALS AND METHODS: In 20 consecutive cases of
      traditional pedicle screw instrumentation under fluoroscopic control the
      effective doses were recorded in vivo and the organ doses then calculated.
      Simulating a spiral CT necessary for the 3-D-model for navigation we defined a
      spiral CT protocol for the instrumented levels and calculated organ and effective
      doses from Monte Carlo Results from CT examinations. RESULTS: Organ doses were
      clearly higher for the CT model than in any of the fluoroscopic procedures in
      vivo. The mean effective dose for the CT model was fifteen times higher than the
      fluoroscopic dose: 7.27 mSv versus 0.48 mSv. CONCLUSIONS: In experienced hands
      open pedicle screw insertion in the thoracic and lumbar spine using fluoroscopy
      control requires a fifteen times lower radiation dose than do CT scans necessary
      for computer-assisted surgery. Regarding the published small percentage of
      neurological complications in traditional screw insertion technique the use of
      computer-assisted surgery in pedicle screw insertion using CT scan should be
      limited to carefully chosen indications. The development of navigation systems
      based on other data sources than CT should be encouraged.

PMID- 12056280
TI  - [Accuracy of fluoroscopic navigation of pedicle screws. CT-based evaluation of
      bone screw placement].
AB  - While the advantages of C-arm navigation in computer-assisted spine surgery are
      obvious, the accuracy of pedicle screw placement with virtual fluoroscopy still
      needs to be verified. The C-arm-based ION system (Medtronic Sofamor Danek) was
      used to navigate pedicle screw insertion in patients undergoing spinal surgery
      for various conditions. In a prospective study, a total of 160 screws were
      inserted in the first 30 consecutive patients since introduction of the system at
      our institution: 54 at the thoracic spine (highest level: TH4) and 106 at the
      lumbar spine. Computed tomography (CT) scans were performed postoperatively by
      two independent radiologists to control the accuracy of screw placement at the
      level of the pedicles after reconstruction of axial images according to Laine et
      al. The comparison of the calculated accuracy rate of pedicle screw placement
      using virtual fluoroscopy with reported results achieved with CT-based navigation
      shows similar results for virtual fluoroscopy and a remarkable increase of
      accuracy in comparison to reports on conventional pedicle screw placement.

PMID- 12056282
TI  - [MACS-TL polyaxial screw XL. A new concept for increasing stability of ventral
      spondylodesis in the presence of dorsal injuries].
AB  - The influence of additional dorsal structure damage on anterior stabilization of
      thoracolumbar fracture is still unknown. Screw cement enhancement is a
      possibility to reinforce the stability of anterior instrumentation. A new
      anchorage system has been developed for fixation of anterior stabilization
      devices, adapted through geometric optimization and the possibility of optional
      additional cementation after screw insertion in cases of poor bone quality. Is
      this enhancement strong enough to support a single anterior procedure such as the
      thoracoscopic technique and still compensate for dorsal instability? A
      biomechanical in vitro study simulating an anterior corpectomy, strut grafting,
      and overbridging stabilization with a dorsal laminectomy as dorsal structure
      damage was performed, and the primary stability parameters were evaluated with
      and without screw cement enhancement. The additional cementation enhanced the
      primary stability of the anterior instrumentation and compensated for dorsal
      instability.

PMID- 12056283
TI  - [Definition of pedicle malposition. Primary stability and loosening
      characteristics of pedicle screws in relation to position: spongious anchoring,
      cortical anchoring, perforation and malposition].
AB  - Totally misplaced pedicle screws will lead to major stability problems. There are
      no publications about the stability behavior of screws, which have no pure
      trabecular position and perforate the pedicle slightly. Since neurological
      problems are only described with screws perforating the pedicle medially by at
      least 4 mm, this question has great relevance concerning the definition of
      pedicular malposition. Sixty-eight pedicle screws were tested in human cadaveric
      lumbar spines. Their vertical path was measured at the beginning and end of 1000
      sinusoidal cycles with a force amplitude of 160 N. They were divided into four
      groups according to their screw position as mentioned in the title. We found no
      significant differences in primary stability or loosening between the groups. The
      cortical contact and perforation groups had slightly better results, which were
      not significant in comparison to the other two groups.

PMID- 12056284
TI  - [Mechanical testing of implant properties of thoracoscopic implantation of
      ventral spinal stabilizing systems. Comparative study with the ISO/DIS 12189-2
      corpectomy model and an improved synthetic model].
AB  - A new modular anterior fixation system MACS TL (modular anterior construct system
      for the thoracic and lumbar spine) has been developed for use in thoracoscopic
      spondylodesis. This system demonstrates high angular stability and meets the
      surgical requirements for an endoscopic approach. The objective of the current
      study was fatigue testing of the MACS TL implant system using a corpectomy model
      according to ISO/DIS 12189-2 and a synthetic model recently developed by Kotani
      et al. [6]. The MACS TL system demonstrated good mechanical properties with a
      high stiffness compared to the published data reviewed. The importance of dynamic
      testing in a corpectomy model has been demonstrated by comparing the MACS TL
      plate system with an early prototype, which has not yet been clinically
      evaluated. The corpectomy model according to Kotani et al. offers an interesting
      alternative to the ISO/DIS 12189-2 test method for asymmetrically designed and
      antero-laterally positioned spinal implants due to the unconstrained ball joint.

PMID- 12056286
TI  - [Sports fitness after prosthetic joint replacement].

PMID- 12056285
TI  - [Development and clinical application of a thoracoscopy implantable plate frame
      for treatment of thoracolumbar fractures and instabilities].
AB  - The evolution of endoscopic spinal approaches and the associated possibilities
      for stabilization of the anterior column demands a new generation of spinal
      implants. Of particular interest is the possibility to implant using an
      endoscopic approach and the ability to achieve real angular stability so that for
      a suitable injury pattern an exclusively anterior procedure can be carried out.
      Since November 1999, a new type of anterior plate, MACS TL, developed to meet
      minimally invasive clinical requirements, has been used in the
      Berufsgenossenschaftliche Unfallklinik in Murnau, Germany for treating the mid
      and lower thoracic and lumbar region. The following reports on the results of the
      first 100 procedures carried out over a period of 15 months, of which 93% were
      performed endoscopically. The results convey a trend toward anterior endoscopic
      treatment of injuries of the anterior column using an implant with angular
      stability. The results now available on healing after fusion indicate the
      favorable influence of the stability provided by the implants on the bone-healing
      rate.

PMID- 12056287
TI  - [Diagnostic imaging in rheumatology].

PMID- 12056288
TI  - [Early diagnosis of chronic polyarthritis with conventional roentgen imaging].
AB  - Radiographs used to be the gold standard of imaging techniques in rheumatoid
      arthritis. New imaging techniques allow more detailed examinations of soft tissue
      changes, the predominant features of early RA. This could change the place of
      radiography especially in this phase of the disease. The best available
      radiographic technique is necessary to capture the changes of early RA.
      Radiographs of both hands and feet are needed for early diagnosis and
      standardized follow-up. Extent and distribution of indirect signs of arthritis
      (soft tissue swelling and juxtaarticular osteoporosis) vary with disease activity
      but can provide important information also for the differential diagnoses. Inter
      reader reliability of these changes is low, thus, questioning the validity of
      these findings. Direct signs of arthritis (erosions and joint space narrowing)
      are more easy to detect and are used for the quantification of the long-term
      disease course, in clinical studies, as proof for the disease modifying property
      of an intervention. Direct signs of arthritis are also found in other diseases,
      so they are not exclusive signs of RA. Nevertheless a typical radiographic
      finding in early RA is highly specific and is the most important risk factor for
      a poor prognosis. Therefore, it serves as the basis for therapeutic decisions,
      e.g., for an early aggressive treatment. As long as there are no data that the
      findings with the new imaging techniques are as relevant for prognosis,
      radiographs cannot be replaced in early RA.

PMID- 12056289
TI  - [Value of arthrosonography in early arthritis diagnosis].
AB  - Sonography of joints and peri-articular soft tissue has become an established
      imaging technique for the diagnosis and follow-up of patients with rheumatic
      diseases. Sonography allows a good differentiation of exsudative and
      proliferative changes of synovialis as well as tenosynovitis. Superficial
      cartilage and bony lesions may be seen before they are apparent on x-rays.
      Sonography is helpful in the diagnosis of early arthritis. Dynamical examination
      of joints allows the detection of structural abnormalities. Sonography can also
      be used for interventional procedures such as joint aspirations, guidance of
      therapy and needle biopsy.

PMID- 12056290
TI  - [Sensitivity and significance of nuclear magnetic tomography findings of finger
      joints in rheumatoid arthritis].
AB  - Evaluation of the sensitivity and value of magnetic resonance imaging (MRI)
      findings and miniarthroscopic investigations (mini-/needle-arthroscopy = MA) of
      metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA). 30
      patients with RA (21 female, 9 male), disease duration 2 months to 22 years and
      mean disease activity score (DAS) of 3.90 (range: 2.00-7.67) were examined by MRI
      of the hand (MCP region) and following MA of the MCP-II joints. MRI parameters
      for arthritis (synovial enhancement, synovial extension, cortical alterations,
      joint gap width) and corresponding macroscopic items (synovial extension,
      synovial hyperemia and vascularity, cortical alterations) by MA, scored
      semiquantitatively for synovitis (graduated from 0-III degree), were correlated.
      Additionally, normal radiographs of the hands were performed and compared with
      MRI findings concerning the detection of bony lesions. Evaluation of the 30 MRI
      and MA examination revealed highly significant correlations (p < 0.0001) for the
      parameters of synovial extension (MRI/MA), cortical alterations (MRI/MA) and
      synovial enhancement (MRI) compared to synovial hyperemia and vascularity (MA).
      We found significant correlations for parameters of activity and chronicity of RA
      pathology as assessed by MRI and MA. The detection rate of cortical lesions by
      MRI was two and a half times higher than by X-ray. MRI findings of MCP-II joints
      compared to those of MCP III-V showed that the MCP-II joint was more strongly
      involved.

PMID- 12056291
TI  - [Synovial membrane diagnostic assessment in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is the most frequent inflammatory rheumatic disease. At
      the beginning of the disease, where, based on today's knowledge the therapeutic
      possibilities are largest, the diagnostic methods do not permit a differentiated
      estimation of the prognosis. Conventional x-rays are mostly normal and serum
      markers unspecific. So far--in contrast to other diseases--only little
      information had been drawn from the pathomorphologic substrate "synovialis"
      itself to assess the prognosis. Reasons therefor were found in difficulties in
      obtaining synovial tissue besides surgical interventions, particularly in
      patients with early arthritis. By minimalizing the diagnostic instruments and
      improvement of the technique, synovial tissue sampling in RA has become minimally
      invasive and it is even possible to perform on the smallest joints, such as
      finger joints. Hereby, synovial analysis is open for detecting pathways of
      inflammation and joint destruction, which might support the advancement of new
      therapeutic strategies, followed by a better prognosis and outcome of RA.

PMID- 12056292
TI  - [New and old therapeutic options in ankylosing spondylitis--is there an
      indication for sulfasalazine?].

PMID- 12056293
TI  - [Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind
      placebo-controlled study and comparison with other controlled studies].
AB  - OBJECTIVE: To assess the efficacy and tolerability of sulfasalazine in ankylosing
      spondylitis including a meta-analysis of comparable trials. METHODS: In a
      prospective, randomized, double-blind, placebo-controlled trial 70 patients with
      established diagnosis of ankylosing spondylitis and a mean disease duration of
      16.7 years were investigated in two centers for 26 weeks comparing 3 g/d
      sulfasalazine to placebo. RESULTS: The main outcome parameters, pain score,
      fingers-to-floor test, and CRP, did not improve significantly in the
      sulfasalazine group compared to the placebo group. Altogether sulfasalazine was
      significantly superior to placebo only concerning the IgA levels. The dropout
      rate was 47% for the sulfasalazine group and 19% for the placebo group. Due to
      side effects, 38% and 11%, respectively, stopped treatment. Ten other
      prospective, double-blind, controlled studies were analyzed. Altogether 959
      patients with a mean disease duration of 13.9 years were evaluated. Most
      parameters did not improve significantly in the sulfasalazine groups compared to
      the placebo groups. Spinal motility remained nearly unchanged (0.3-3.5%
      improvement). Pain, morning stiffness, functional index, and global assessment
      were slightly influenced (1.9-11.7%). Reduction of ESR, CRP, IgA, IgG, and IgM
      was more distinct (12.6-20.3%). In 4 studies SSZ had greater efficacy in patients
      with peripheral joint involvement. CONCLUSION: Sulfasalazine has no clinically
      relevant benefit in patients with ankylosing spondylitis. The dropout-rate due to
      adverse effects is high with a daily dose of 3 g. Sulfasalazine may be beneficial
      in peripheral joint involvement. Only few data exist about patients with a
      disease duration of less than 10 years.

PMID- 12056294
TI  - Pulmonary function in children with juvenile idiopathic arthritis and effects of
      methotrexate therapy.
AB  - OBJECTIVE: To evaluate impairment of lung function as an adverse effect
      associated with methotrexate therapy in patients with juvenile idiopathic
      arthritis (JIA). METHODS: We performed pulmonary function testing including
      diffusion capacity for carbon monoxide as measured by the single breath method
      (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were
      treated with methotrexate for a median of 24 months (range 3 to 120 months).
      Except for the presence of asthma in two children, there was no clinical or
      radiological evidence of pulmonary disease. RESULTS: Pulmonary function testing
      demonstrated moderate airway obstruction in two children with known bronchial
      asthma. Neither obstructive nor restrictive alteration of ventilation was found
      in any other patient. Two juvenile idiopathic arthritis patients showed a reduced
      CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate.
      CONCLUSIONS: With regard to lung function impairment treatment with low dose
      methotrexate appears to be safe even when performed for several years reaching a
      total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid
      arthritis patients, in children with juvenile idiopathic arthritis impairment of
      lung function is a rare event.

PMID- 12056295
TI  - [Chrysiasis].
AB  - We describe the case of a 78-year old woman, with rheumatoid arthritis, 3 years
      of regular parenteral gold administration and Chrysiasis. Chrysiasis is a rare
      permanent pigmentation of the skin resulting from the parenteral administration
      of gold. The cause of the pigmentation is multifactorial and not fully
      established at the moment.

PMID- 12056296
TI  - [Fulminant course of diffuse alveolar hemorrhage in systemic lupus erythematosus-
      a case report].
AB  - A 31-year old male patient had suffered from systemic lupus erythematosus (SLE)
      for 21 years. During the last 8 years he exhibited no clinical symptoms and did
      not receive any medical SLE treatment. He was admitted with a two-day history of
      dyspnea and fever. Laboratory studies revealed microcytic anemia and elevated
      levels of inflammation markers. Chest X-ray showed pulmonary infiltrates. The
      respiratory status rapidly deteriorated and the patient died 16 hours after
      admission. An autopsy was performed and diffuse alveolar hemorrhage in all parts
      of the lungs were seen, which was confirmed by microscopic examination. In
      contrast, lung histology did not show evidence of infection or inflammatory
      lesions. Additionally, membranous glomerulonephritis could be identified by light
      and electron microscopy. Diffuse alveolar hemorrhage (DAH) and concomittant lupus
      nephritis as manifestations of the known SLE were diagnosed. Acute pulmonary
      hemorrhage was determined as the cause of death. DAH is a rare, but serious
      manifestation of SLE. The diagnosis is difficult since the occurrence is abrupt
      and both symptoms and histology of the lesion are non-uniform and unspecific. The
      present case demonstrates that DAH also develops in patients that have not had
      clinical symptoms for several years. Since the early diagnosis is essential for
      the outcome, DAH should be considered in every case of SLE patients with severe
      pulmonary symptoms. Corticosteroids are the recommended form of therapy for this
      disorder.

PMID- 12056297
TI  - [Technique and value of arthrosonography in rheumatologic diagnosis. 2:
      Ultrasound diagnosis of the hip area].
AB  - The clinical investigation of the hips in patients with rheumatic diseases is
      often equivocal. Thus, ultrasonography of this region is very relevant for
      rheumatologists. We suggest following standard scans: 1) anterior longitudinal
      scan to detect synovitis of the hip joint, iliopectineal bursitis, irregularities
      of the bone surface in osteoarthritis, Perthes' disease, and erosions due to
      inflammatory disease, 2) anterior transverse scan to evaluate these structures in
      an additional dimension, 3) lateral longitudinal scan of the hip joint with the
      same objective as the above mentioned scans; 4) lateral longitudinal scan, and 5)
      lateral transverse scan of the greater trochanter to diagnose trochanteric
      bursitis and bone irregularities due to enthesiopathy, and 6) dorsal oblique scan
      (optional) to diagnose hip joint effusions and pannus that localize in the dorsal
      region. Rotation of the joint is necessary to detect small effusions. The
      transducers should have a medium frequency of 5 to 7.5 MHz. In obese or muscular
      patients, 3.5 MHz transducers may be necessary to increase penetration. The
      anterior distance between the bone and the joint capsule of the hip joint is > or
      = 7 mm in probable and > or = 8 mm in definite synovitis or effusions. Synovitis
      or effusions are probable if the difference between right and left hip is > or =
      2 mm, and they are definite if the difference is > or = 3 mm.

PMID- 12056298
TI  - [Drug therapy and malpractice exemplified by combination leflunomide and
      methotrexate therapy].

PMID- 12056299
TI  - [Leflunomide + methotrexate combination therapy from the physician's viewpoint].

PMID- 12056300
TI  - [Neuroendocrine-immunologic mechanisms in rheumatic diseases--a congress report].
AB  - Neuro-endocrine immune mechanisms play an important immunomodulatory role for
      rheumatic diseases as evidenced by long-recognized effects of glucocorticoids,
      gender, pregnancy, hemiparalysis, and stress on various clinical and
      epidemiological aspects. Recently, some regulatory pathways have been identified
      between the neuroendocrine and immune systems which seem to be altered in these
      diseases. Cooperation between the autonomic nervous system and the hypothalamic
      pituitary adrenal axis (HPA axis) is important to dampen the reaction of the
      immune system. In chronic inflammatory diseases such as rheumatic diseases these
      systems have become deficient. Moreover, hyperexcitability of sensory nerves due
      to peripheral and central neuronal sensitization can support the local
      inflammatory process.

PMID- 12056301
TI  - [A victim of Stalin's politics? Wladimir Michailowitsch Bechterew (1857-1927)].

PMID- 12056303
TI  - Identifying stressors on families.

PMID- 12056304
TI  - Standing in the health gap.

PMID- 12056302
TI  - [What common grounds exist in the pathomechanism of Sjogren disease and
      associated hematologic diseases? From autoreactive B cell activation and T cell
      cooperation to B-cell lymphoma. Pathogenesis of lymphoproliferations in patients
      with Sjogren syndrome].

PMID- 12056305
TI  - Delivering a safe and accessible service to Maori.

PMID- 12056306
TI  - Do new graduate midwives need extra support?

PMID- 12056307
TI  - Lending a hand to families.

PMID- 12056308
TI  - The home care industry--'growing like topsy' and under stress.

PMID- 12056309
TI  - Maintaining professional and personal accountability.

PMID- 12056310
TI  - Maori need to take responsibility for their own health.

PMID- 12056311
TI  - Caregivers in the community are largely invisible.

PMID- 12056312
TI  - Dying in the curative system: the haematology/oncology dilemma. Part 2.
AB  - It is now beginning to be understood that a particularly problematic area in
      oncology in relation to palliative care is that of haematology. Family members
      and carers who have experienced the institutional deaths of loved ones speak of
      their experiences with concern indicating a dire need for changes to present
      practice. Recommendations arising from this comparative research are included.

PMID- 12056313
TI  - Pranic healing: an energy-based healing practice for the contemporary nurse.
AB  - This paper argues for the introduction of Pranic Healing (PH), an energy-based
      complementary healing technique, within clinical nursing practice. It explores
      the ideological foundation of PH and its potential to promote clients' well
      being. Selected 'scientific discoveries' supporting the efficacy of energy
      therapies, such as PH, are noted.

PMID- 12056314
TI  - On finding meaning in the experience of illness.

PMID- 12056315
TI  - Compromising and containing: self-management strategies used by men and women who
      live with multiple sclerosis and urinary incontinence.
AB  - This study aimed to expose the experiences of men and women living with Multiple
      Sclerosis (MS) and how they manage the challenge of urinary incontinence in their
      lives. We explore the commonalities and diversities between men and women living
      with MS and urinary incontinence and conclude the paper by making recommendations
      for nursing practice.

PMID- 12056317
TI  - Touching the fragile baby: looking at touch in the special care nursery (SCN).
AB  - This article will briefly demonstrate that touch promotes bonding and well-being
      and is therefore an essential therapy for the benefit of parents, babies, and
      health care professionals. Guideline suggestions for the safe introduction of
      touch therapy are presented. The author acknowledges that her own work practice
      has been positively influenced after conducting this investigation into touch and
      the pre-term infant.

PMID- 12056316
TI  - Grasping the essence of the spiritual dimension reflected through the horizon of
      suffering: an interpretative research synthesis.
AB  - The purpose of this research synthesis was to describe the essence of the
      spiritual dimension reflected through the horizon of suffering. The material
      reviewed consisted of 18 articles published between 1989 and 2000 in caring and
      nursing journals. A depth in the interpretation of the texts was discovered where
      four different themes emerged: undemanding communion, confirmation of dignity,
      the dialectic of suffering, and the creation of coherence of meaning.

PMID- 12056318
TI  - Nursing in 2002: a personal view.

PMID- 12056320
TI  - Respect + recognition = reconciliation.

PMID- 12056319
TI  - HIV toll puts strain on SA nurses.

PMID- 12056321
TI  - Trading away our health care?

PMID- 12056322
TI  - Lies, damn lies and research.

PMID- 12056323
TI  - Nurses suspended pending inquiry into deaths.

PMID- 12056324
TI  - Using ultrasound to assess bladder function in aged care rehabilitation.

PMID- 12056325
TI  - Pre-irradiation at a low dose-rate blunted p53 response.
AB  - We investigated whether chronic irradiation at a low dose-rate interferes with
      the p53-centered signal transduction pathway induced by radiation in human
      cultured cells and C57BL/6N mice. In in vitro experiments, we found that a
      challenge with X-ray irradiation immediately after chronic irradiation resulted
      in lower levels of p53 than those observed after the challenge alone in
      glioblastoma cells (A-172). In addition, the levels of p53-centered apoptosis and
      its related proteins after the challenge were strongly correlated with the above
      mentioned phenomena in squamous cell carcinoma cells (SAS/neo). In in vivo
      experiments, the accumulation of p53 and Bax, and the induction of apoptosis were
      observed dose-dependently in mouse spleen at 12 h after a challenge with X-rays
      (3.0 Gy). However, we found significant suppression of p53 and Bax accumulation
      and the induction of apoptosis 12 h after challenge irradiation at 3.0 Gy with a
      high dose-rate following chronic pre-irradiation (1.5 Gy, 0.001 Gy/min). These
      findings suggest that chronic pre-irradiation suppressed the p53 function through
      radiation-induced signaling and/or p53 stability.

PMID- 12056326
TI  - Significance of the response of quiescent cell populations within solid tumors in
      cancer therapy.
AB  - In analyzing the response of quiescent (Q) cells in solid tumors, we have
      developed a combined method with a micronucleus (MN) assay and the identification
      of proliferating (P) cells by 5-bromo-2'-deoxyuridine (BrdU) and an anti-BrdU
      monoclonal antibody. Using this method, the responses of Q tumor cells as well as
      total tumor (P + Q) cells within murine solid tumors to various DNA-damaging
      treatments were evaluated. Based on this evaluation, combining with tirapazamine,
      a well-known bioreductive agent, and/or heat treatment at mild temperatures was
      thought to be a promising modality for cancer therapy in terms of conventional
      anticancer treatment-resistant Q cell control. Recently, our method for detecting
      the Q-cell response using P cell labeling with BrdU and the MN frequency assay
      was also shown to be applicable to an apoptosis detection assay. Meanwhile, our
      method for detecting the intratumor Q-cell response was also applicable toward
      high linear energy transfer radiation, including reactor neutrons. Thus, using
      our method, a new neutron capture compound that has the potential to be
      distributed in neutron capture therapy-resistant intratumor Q cell populations is
      now under development.

PMID- 12056327
TI  - In vitro radiation-induced effects on rat tracheal epithelial cells. I) Different
      radiosensitivity of cell inactivation after alpha and gamma irradiations.
AB  - In order to compare the radiotoxicity of alpha- and gamma-irradiations, primary
      cultures of tracheal epithelial cells from two rat strains, Sprague Dawley (SD)
      and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated with 241Am alpha
      particles or 60 Co gamma-rays. The survival ratio for each of the two rat strain
      cells appeared to be statistically different after high-LET irradiation. WF/Fi
      rat cells were 1.7-times more radiosensitive than SD rat cells, whereas no
      difference was observed following low-LET irradiation. A comparison of the cell
      survival yielded RBEs of 2.8 and 4.5 for SD and WF/Fi rat cells, respectively. As
      previously observed, with increasing LET of particles, the cell-survival curves
      approximate an exponential function of the dose. On the contrary, for low-LET,
      the survival curves showed a marked initial shoulder. This in vitro cellular
      model, using epithelial cells of the upper airway, provides a suitable system to
      estimate the mechanism involved in radiosensitivity after high-LET irradiation.
      The responses to radiation-induced lethal effects within a same type of cell were
      dependent on the irradiation parameters, but might be modulated by the individual
      sensitivity under genetic or epigenetic factor controls.

PMID- 12056328
TI  - In vitro radiation-induced effects on rat tracheal epithelial cells. II)
      Different preneoplastic cell transformation after alpha and gamma irradiations.
AB  - In order to compare the cell transformation induced by alpha- and gamma
      irradiation, primary cultures of tracheal epithelial cells from two rat strains,
      Sprague Dawley (SD) and Wistar Furth/Fisher F344 (WF/Fi) rats, were irradiated
      with 241Am alpha-particles or 60 Co gamma-rays. The relative transformation
      frequency (RTF) for WF/Fi primary cells was very close to the level of the
      spontaneous incidence and independent on the two irradiation types used. On the
      contrary, the RTF for the SD primary cells increased with a decrease of the LET
      radiation when the relative survival was higher than about 40%. Therefore, the
      RTF values reached 4-5 for alpha-particles and 10-12 for gamma-rays. The RTF can
      be related to the intrinsic radiosensitivity of the rat epithelial cells.
      However, the difference in the radiation-induced RTF for SD or WF/Fi primary
      cells seems to be due to the development, under genetic control, of the initial
      lesion to the neoplastic state.

PMID- 12056329
TI  - A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer
      cells exposed to high-dose irradiation under hypoxia.
AB  - The radiosensitizing effects of PR-350, a nitroimidazole derivative, were
      examined concerning the cell killing of human pancreatic cancer cell lines
      exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead
      cells were analyzed with a multiwell plate reader to measure the fluorescence
      intensity of propidium iodide before and after a digitonin treatment. The
      sensitizing effect of PR-350 on cell killing by high-dose irradiation was
      confirmed by time-course, dose-dependency, and microscopic observations. In five
      of seven pancreatic cancer cell lines in which the number of dead cells was
      determined 5 days after 30 Gy irradiation in the presence of PR-350, the number
      was significantly increased under hypoxic conditions, but not under aerobic
      conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was
      also confirmed by flow cytometry. The results indicate that PR-350 can enhance
      the killing of pancreatic cancer cells by high-dose irradiation under hypoxia,
      which supports its clinical radiosensitizing effects when administered during
      intraoperative irradiation to pancreatic cancer.

PMID- 12056330
TI  - Reassessment of the cancer mortality risk among Hiroshima atomic-bomb survivors
      using a new dosimetry system, ABS2000D, compared with ABS93D.
AB  - The aim of the present study was to examine the excess relative risk for leukemia
      mortality and all cancers, except leukemia, among Hiroshima atomic-bomb survivors
      by applying ABS93D and ABS2000D. Particular attention was given to any difference
      in the neutron-dose estimates between the two dosimetry systems. The study
      subjects were 51,532 atomic-bomb survivors registered in a database of the
      Research Institute for Radiation Biology and Medicine of Hiroshima University
      (RIRBM). The results obtained by both dosimetry systems are similar: the excess
      relative risk per Sv for leukemia mortality and all cancers except leukemia is
      significantly higher compared to the control group. In addition, the difference
      in the excess relative risks between the two systems is not significant.
      Therefore, it is indicated that a modification of the neutron-dose estimates
      would not markedly change the conclusions about the cancer mortality risk.

PMID- 12056331
TI  - The quality of DNA recovered from the archival tissues of atomic bomb survivors
      is good enough for the single nucleotide polymorphism analysis in spite of the
      decade-long preservation in formalin.
AB  - It is well known that the yield of DNA recovered form tissues preserved in
      formalin is inversely proportional to the stored duration. How is the quality? We
      tested the quality of DNA from archival tissues of atomic-bomb survivors stored
      in formalin for decades with the parameters of gene amplification efficiency by a
      polymerase chain reaction. All of the DNA extracted from the tissues preserved in
      formalin for 30 years amplified the 54- and 61-base pairs of the DNA fragments
      successfully. The direct sequencing of the PCR products confirmed the accurate
      amplification of the target sequence. A further trial to amplify the longer
      sequence of 111 base pairs succeeded in 20% of the samples tested. From these
      results, we propose a new utility of archival samples for the analysis of single
      nucleotide sequence polymorphism of genes, no matter how long the samples have
      been preserved in formalin.

PMID- 12056332
TI  - Radiation-chemical properties of the hypoxic cell radiosensitizer doranidazole
      (PR-350).
AB  - This study was performed to confirm the radiation-chemical properties of the 2
      nitroimidazole derivative doranidazole, (+/-)-(2RS,3SR)-3-[(2-nitroimdazol-1-yl)
      methoxy]butane-1,2,4-triol [CAS 137339-64-1], PR-350, which was synthesized as a
      hypoxic cell radiosensitizer with low toxicity. Radiation-chemical experiments
      using doranidazole showed that (1) unlike O2, it had high reactivity toward not
      only hydrated electrons (eaq-), but also hydroxyl radicals (.OH), (2) the reduced
      intermediates of doranidasole had no ability to induce immediate strand breaks of
      colE1 plasmid DNA, (3) doranidazole enhanced radiation-induced DNA strand breaks
      of colE1 plasmid DNA in the aqueous state, whereas it did not enhance the base
      alteration, such as 8-oxo-deoxyguanosine, (4) it enhanced the radiation-induced
      formation of strand breaks with 3'-phosophate and 3'-phosphoglycolate termini,
      and (5) it was bound to DNA after irradiation. These facts revealed that the
      majority of radiation-chemical properties of doranidazole, except for the high
      reactivity toward OH, were similar to those of oxygen.

PMID- 12056333
TI  - Types and three-dimensional distribution of neuronal ectopias in the brain of
      mice prenatally subjected to X-irradiation.
AB  - The types and three-dimensional distribution of neocortical ectopias following
      prenatal exposure to X-irradiation were studied by a histological examination and
      computer reconstruction techniques. Pregnant ICR mice were subjected to X
      irradiation at a dose of 1.5 Gy on embryonic day 13. The brains from 30-day-old
      mice were serially sectioned on the frontal plane at 15 microns, stained with HE
      and observed with a microscope. The image data for the sections were input to a
      computer, and then reconstructed to three-dimensional brain structures using the
      Magellan 3.6 program. Sectional images were then drawn on a computer display at
      240 microns intervals, and the positions of the different types of neocortical
      ectopias were marked using color coding. Three types of neocortical ectopias were
      recognized in the irradiated brains. Neocortical Lay I ectopias were identified
      as small patches in the caudal occipital cortex, and were located more laterally
      in the neocortex in caudal sections than in the rostral sections. Periventricular
      ectopias were located more rostrally than Lay I ectopias, and were found from the
      most caudal extent of the presumed motor cortex to the most caudal extent of the
      lateral ventricle. Hippocampal ectopias appeared as continuous linear bands, and
      were frequently associated with the anterior parts of the periventricular
      ectopias.

PMID- 12056334
TI  - Redox reactions of tocopherol monoglucoside in aqueous solutions: a pulse
      radiolysis study.
AB  - The reactions between tocopherol monoglucoside (TMG), a water-soluble vitamin-E
      derivative, with Br2.-, N3., (SCN)2.-, NO2., OH. and various halogenated peroxyl
      radicals were examined using a pulse radiolysis technique. The results
      demonstrate that TMG forms a stable phenoxyl radical at pH > 6.8. The thus-formed
      phenoxyl radical shows pH-dependent decay kinetics and is disproportionated by
      2nd order kinetics at pH 2.3. It was observed that the TMG reactivity towards a
      halogenated peroxyl radical increases with the number of halogen atoms at the
      carbon atom having a peroxyl group. The reaction between the TMG phenoxyl radical
      and ascorbic acid was also examined using a pulse radiolysis technique. The
      results indicate that the TMG phenoxyl radical is repaired by ascorbate. Kinetic
      studies indicate that TMG may act as an antioxidant to repair free-radical damage
      to some biologically important compounds. The one-electron reduction potential
      for TMG was found to be 0.522 V +/- 0.06 vs. NHE.

PMID- 12056335
TI  - Improvement after traumatic brain injury achieved by coordination dynamic
      therapy.
AB  - In 6 patients 13 to 47 years old, who suffered traumatic brain injury 2 to 7
      years ago, central nervous system (CNS) functioning, including motor, vegetative
      and higher mental functions, could partly be restored by applying coordination
      dynamic therapy for 3 months. The repair was quantified by the improvement of
      walking, jumping and hand function and the direct measurement of the coordination
      dynamics of coordinated arm, leg and trunk movements. The CNS organization (the
      coordination dynamics) improved by 69% from 29 to 5.9 s-1 within 3 months of
      therapy. The mean coordination dynamics achieved (5.9) were slightly higher than
      those in a population of untrained healthy physiotherapists (coordination
      dynamics = 5.1 +/- 1.2). The author's value of coordination dynamics is mostly
      between 3 and 4 (best value 2.5). It is discussed that longer therapy times are
      needed in neurorehabilitation, since there is indication that during longer
      therapy times also new nerve cells are built outside the hippocampus, for example
      in the spinal cord.

PMID- 12056336
TI  - Evaluation of postural tremor of finger for neuromuscular diseases and its
      application to the classification.
AB  - The purpose of this study is to verify the features of the power spectrum of
      postural tremors for neuromuscular disease patients and to classify the postural
      tremors. The subjects were 88 neuromuscular disease patients (30 Parkinson
      disease (PD), 25 cerebellar disease (CER), 7 multiple sclerosis (MS), 7
      neuropathy (NEU), 10 motor neuron disease (MND), 9 myopathy (MYO)). The control
      subjects were 12 normal young persons and 10 normal aged persons. Postural tremor
      was detected by accelerator sensor. Postural tremor was recorded under the two
      postural conditions: The subjects maintained the index finger without or with a
      weight load of 50 g in a horizontal position while looking at a visual target in
      front of the tip of the index finger. The power spectrum was calculated by an
      auto-regressive model (AR model). The peak frequency and the peak power were
      evaluated under the two conditions. Two frequency components of 8-12 Hz and 20-25
      Hz appeared in the postural tremor of both normal subjects and neuromuscular
      disease patients. The difference of the postural tremor between the subjects
      mainly appeared in the 8-12 Hz component during the postural tremor with a weight
      load. MYO patients belonged to one group (called as group P1) due to lower peak
      power, CER patients belonged to one group (called as group P2) due to higher peak
      power, and PD and MS patients belonged to one group (called as group P3) due to
      lower peak frequency and higher peak power. NER and MND patients belonged to one
      group (called as group N which meant normal group). These results suggested that
      the peak frequency and the peak power of the 8-12 Hz component were changed by
      the conditions of both spinal reflex system and central nervous system. An
      oscillator within the central nervous system produced the underlying frequency of
      8-12 Hz component, while the amplitude of 8-12 Hz component was governed by both
      spinal reflex system and central nervous system. In conclusion, the
      classification of postural tremor for neuromuscular disease patients was a useful
      index to elucidate the mechanism of tremor oscillation and to assist in clinical
      diagnosis of neuromuscular disease.

PMID- 12056337
TI  - Surface detected potentials of normal and reinnervated motor units: a simulation
      study for muscles consisted of short fibres.
AB  - We aimed to check whether the characteristics used up to now in macro EMG to
      distinguish between normal and reinnervated motor unit potentials (MUPs), were
      suitable for surface detected MUPs. MUPs produced by normal and reinnervated MUs
      were simulated with a fast and precise convolution model. An increased number of
      fibres in the MU territory enhanced the amplitude, area and RMS of the MUP
      proportionally irrespective of the MU-electrode distance. An increased scatter of
      the end-plates and greater desynchronization in the fibres' activation decreased
      the MUP amplitude and affected the temporal characteristics of the MUP (duration
      of the negative phase and its area to amplitude ratio). The effects were more
      pronounced at shorter distances. At larger distances, the effect of the MU
      electrode distance on temporal and amplitude characteristics of MUPs was much
      stronger than that of the parameters changed with reinnervation. We conclude that
      reinnervated MUs consisting of short fibres can not be distinguished from the
      normal ones by means of characteristics of MUP used in macro EMG. To discriminate
      reinnervated MUs non-invasively, the MUP amplitude should be normalized in
      respect of the MU-electrode distance or other MUP characteristics (independent of
      MU-electrode distance and sensitive to reinnervation) should be used.

PMID- 12056338
TI  - The presence of unknown layer of skin and fat is an obstacle to a correct
      estimation of the motor unit size from surface detected potentials.
AB  - To overcome problems with a strong distance-dependence of the motor unit
      potentials (MUPs), different methods to estimate the MU location and size have
      been proposed. Distance-independence of the exponent of the power function, that
      describes the MUP distance decline, and homogeneity of the volume conductor, are
      assumed in all methods. Some of them consider the exponent value as unique,
      irrespective of persons, muscles and their functional state. One method estimates
      the current exponent value. We evaluate this method by computer simulation of
      MUPs in infinite and semi-infinite volume conductor. Our results show that
      although the first assumption is not fulfilled, it does not affect considerably
      the estimate of the MU location and size obtained for infinite or semi-infinite
      homogeneous volume conductor. The errors of the MU location can be insignificant
      even in inhomogeneous volume conductor with a layer of lower conductivity (skin
      and fat) between the muscle tissue and electrode. The accurate location of the MU
      electrical axis is, however, not a sufficient condition for a correct MU size
      estimation that depends considerably on actual parameters of the layer. Thus, the
      surface EMG could hardly be considered as non-invasive alternative to macro EMG
      for detection of the enlarged MUs.

PMID- 12056339
TI  - Evidence in support of a feedback-sensitive central timekeeper for an over
      learned repetitive motor behavior (pencil shading).
AB  - PURPOSE: To demonstrate the presence of a CNS timekeeper for an over-learned
      repetitive voluntary movement (pencil shading), and to learn if the timekeeper is
      influenced by changes in sensory feedback. METHODS: Self-paced pencil shading;
      fast, maximally-fast, and slow hand waving, as well as enhanced physiologic
      tremor (EPT) were recorded on 3 separate occasions with a surface-mounted
      accelerometer placed on the hand in 9 normal volunteers. Variation in inter-trial
      peak frequency was calculated. Shading and EPT were also recorded with and
      without visual masking in 9 normals and in 2 deafferented patients. Variation in
      intra-trial beat-to-beat intervals, a measure of movement regularity, was
      calculated. RESULTS: Shading and maximally-fast waving displayed preferred
      frequencies with no more variability in peak frequency between trials than did
      EPT, while slow and fast waving had significant inter-trial variability.
      Variation in beat-to-beat intervals for the shading task was less in controls
      than for EPT, and less in controls than for the patients in both the masked and
      unmasked conditions. In addition, in the masked condition, pencil shading by the
      patients was performed with much higher amplitude and lower frequency than by the
      controls. CONCLUSIONS: These data support the hypothesis that certain repetitive
      voluntary movements, such as pencil shading, are paced by central timekeepers
      that are influenced by changes in sensory feedback.

PMID- 12056340
TI  - Needle electromyography in carpal tunnel syndrome.
AB  - The role of needle electromyography (EMG) in the routine evaluation of carpal
      tunnel syndrome (CTS) is not clear. The aim of this study was to determine if
      needle EMG examination of the thenar muscles could provide useful information in
      addition to the nerve conduction (NC) studies. Electrophysiologic procedures
      performed on 84 patients (103 hands) consistent with CTS were reviewed. The
      median thenar motor NC data were matched with the needle EMG findings in the
      abductor pollicis brevis (APB) muscle. The severity of the needle EMG findings in
      the APB muscle correlated well with the severity of the motor NC data. As the
      thenar compound muscle action potential amplitude decreased and the degree of
      nerve conduction slowing and block across the wrist increased, there was a
      corresponding increase in the number of enlarged motor units and decrease in the
      recruitment pattern in the needle EMG findings. Needle EMG examination confined
      to the thenar muscles in CTS does not seem to provide any further information
      when the NC data had already established this diagnosis, and it should not be
      performed routinely.

PMID- 12056341
TI  - The challenge of laboratory monitoring of HIV.

PMID- 12056342
TI  - Day clinics and hospitals--a cost comparison.

PMID- 12056343
TI  - An explanation, please!

PMID- 12056344
TI  - Compulsory HIV testing of sexual offenders.

PMID- 12056345
TI  - An unusual case of hydrocephalus.

PMID- 12056346
TI  - When medical politics and doctors clash.

PMID- 12056347
TI  - PMTCT--who decides on the right to life?

PMID- 12056348
TI  - A provincial headache no pill can cure.

PMID- 12056349
TI  - SAMA ethical guidelines: rights of access to care, clinical independence and
      occupational injuries.

PMID- 12056351
TI  - The culturally sensitive medical consultation.

PMID- 12056350
TI  - The state attitude to antiretroviral treatment--the doctor's duty to speak out.

PMID- 12056352
TI  - Prescription of third-generation cephalosporins for upper respiratory tract
      infections in the Port Elizabeth area.

PMID- 12056353
TI  - Teaching young docs old tricks--was Aristotle right? An assessment of the skills
      training needs and transformation of interns and community service doctors
      working at a district hospital.

PMID- 12056354
TI  - Pulmonary arteriovenous malformation.

PMID- 12056355
TI  - Youth at risk--dieting and eating disorders: a South African perspective.

PMID- 12056356
TI  - Erythrocyte sedimentation rates equal to or above 100 mm/h in the pre-AIDS era.

PMID- 12056357
TI  - Lamellar body counts--a rapid, reliable and cost-effective primary assay for
      fetal lung maturity determination.

PMID- 12056358
TI  - Patients' knowledge and beliefs regarding anaesthetic management.

PMID- 12056359
TI  - A comparison of plasma and whole blood glucose measurements in newborn infants.

PMID- 12056360
TI  - Unpaid community volunteers--effective providers of directly observed therapy
      (DOT) in rural South Africa.
AB  - OBJECTIVE: To illustrate successes and difficulties for the South African
      National Tuberculosis Programme in a rural area. DESIGN: Prospective cohort
      study. SETTING: Sekhukhuneland, Provincial Health Service Southern Region,
      Northern Province, South Africa. SUBJECTS: All patients diagnosed with
      tuberculosis (TB) in the catchment area of four rural hospitals between January
      1997 and June 1999. MAIN OUTCOME MEASURES: Standard outcomes for TB treatment as
      defined by the World Health Organisation. Treatment failure, treatment
      interruption and death were grouped as poor outcomes. RESULTS: One thousand four
      hundred and seventy-six people were diagnosed with TB. The majority (76%) had
      smear-positive pulmonary disease. Treatment was given by directly observed
      therapy (DOT) throughout in all but 15 instances. Excluding 10 subjects with
      known multidrug-resistant TB (MDRTB), 723 (66%) were cured, 68 (6%) completed
      treatment, 73 (7%) interrupted treatment, 37 (3%) failed treatment, 66 (6%)
      transferred out, and 134 (12%) died. Of the 920 initially smear-positive patients
      who survived the first 2 months to receive DOT in the community, 693 (75%) were
      supervised by unpaid community volunteers. Poor outcomes were no more common
      among patients supervised by these volunteers than among patients supervised by
      professional health care workers. Male gender (odds ratio 1.38, 95% confidence
      interval 1.02, 1.87) was significantly associated with a poor outcome.
      CONCLUSION: Although there were difficulties, the national programme was
      successfully applied with no additional funds or facilities. Explanations for the
      high death rate and poor outcomes for men need to be found. Great efforts will be
      required to preserve the quality of the TB programme if it is devolved to primary
      care level.

PMID- 12056361
TI  - Effects of a novel bicycle saddle on symptoms and comfort in cyclists.
AB  - BACKGROUND: While the bicycle frame and other parts of the bicycle have undergone
      many improvements, the bicycle saddle has remained relatively unchanged since it
      was first designed more than 100 years ago. Given the number and range of cycling
      injuries believed to result from the saddle, this is surprising. This study
      investigated the effects of a novel bicycle saddle on saddle-related comfort and
      symptoms during cycling. METHOD: Eleven competitive or recreational cyclists, 6
      females and 5 males, performed three 2-hour stationary cycle rides in the
      laboratory, using their personal bicycles. Ride 1 was performed using the
      standard bicycle saddle and rides 2 and 3 using the novel bicycle saddle.
      Subjects reported saddle comfort rating scores (SC) while using the different
      saddles. Subjects also completed a questionnaire evaluating saddle symptoms (SS)
      when using either the conventional or the novel bicycle saddle during daily
      cycling. RESULTS: The most common saddle-related medical complaint with chronic
      use of the conventional saddle was painful pubic bones, with or without chaffing.
      Others were severe chaffing, saddle sores, chaffing and back pain, and painful
      pubic bones associated with a loss of feeling in the pelvic area. The mean SS
      rating score during the 2-hour laboratory ride was significantly less for the
      novel saddle (11.6 +/- 1.2 versus 19.1 +/- 3.2 arbitrary units, P < 0.01).
      Similarly the mean SC score was significantly lower for the novel saddle (36.2 +/
      10.5 v. 54.7 +/- 11.2 arbitrary units). Values for both SC scores were similar
      for rides 2 and 3. On completion of the trial all subjects indicated that they
      would continue to use the novel saddle in preference to the conventional saddle.
      Three months later 9 subjects (82%) reported continued use of this saddle in
      preference to the conventional saddle. CONCLUSION: These results show
      conclusively that this novel bicycle saddle: (i) significantly reduced reported
      symptoms during daily cycling compared with the conventionally designed cycling
      saddle; (ii) significantly improved saddle comfort during 2-hour cycles in the
      laboratory, such that (iii) when given the option the majority (82%) of the
      subjects chose to use this saddle 3 months later. Furthermore, the beneficial
      effects of the novel saddle were apparent during its first use, suggesting that
      the novel saddle is effective because the design is anatomically correct.

PMID- 12056362
TI  - Effect of a mother-to-child HIV prevention programme on infant feeding and caring
      practices in South Africa.
AB  - OBJECTIVES: To conduct a rapid assessment of the impact of the Khayelitsha
      Prevention of Mother-to-Child Transmission (MTCT) programme on infant care
      practices among programme participants and the local population. STUDY DESIGN:
      Cross-sectional survey and qualitative in-depth interviews. SETTING. Khayelitsha,
      a large formal and informal settlement of about 300,000 people on the outskirts
      of Cape Town. At the time of the study the HIV seroprevalence rate among
      antenatal women was about 15% and the MTCT programme had enrolled nearly 800
      infected women. SUBJECTS: Seventy randomly selected caregivers with young
      children in the survey; in-depth structured interviews with 11 nutrition
      counsellors and 11 mothers enrolled in the programme. RESULTS: Caregivers have
      good knowledge of the spread and prevention of HIV. A majority knew that breast
      feeding can transmit HIV but 90% stated that this did not affect their feeding
      decisions. Over 80% had stopped exclusively breast-feeding by the time their
      infants were 3 months of age. All of the respondents felt that being diagnosed
      HIV-positive would result in serious social and domestic consequences. None of
      the health workers could correctly estimate the risk of spreading HIV through
      breast-feeding and many reported feeling confused about what they should counsel
      mothers. All the mothers on the programme reported exclusive formula-feeding.
      Some had serious problems with preparation and feeding of formula milk. Nearly
      all reported running out of feeds before being able to fetch new supplies. None
      reported any negative social effects of not breast-feeding. Most of the mothers
      endorsed the programme and felt that it had given them strength to face up to and
      plan for the consequences of their diagnosis. CONCLUSION: This rapid appraisal of
      the infant feeding and care component of the MTCT programme has raised a number
      of important challenges which health managers and policymakers need to address.
      Similar assessments in the new pilot sites will be important.

PMID- 12056363
TI  - Focal segmental glomerulosclerosis in malignant hypertension.
AB  - OBJECTIVE: Focal segmental glomerulosclerosis (FSG) may occur in primary
      malignant hypertension (MHT) either as a result of glomerular hyperfiltration or
      fibrinoid necrosis (FN), and may contribute to renal dysfunction. To determine
      the frequency of occurrence and distribution of FSG in primary MHT we studied
      renal biopsy specimens from 38 black Africans--30 postmortem and 8 needle-biopsy
      specimens. SUBJECTS: There were 31 male subjects and 7 female, with a mean age of
      46 (+/- 7) years. RESULTS: Mean blood pressure (BP) was 206 +/- 15/137 +/- 9
      mmHg, median 24-hour proteinuria (interquartile (IQ) range) was 5.1 g (3.3-6.5
      g), median serum albumin 3.4 g (3.2-3.8 g) and median serum creatinine 540
      mumol/l (425-752 mumol/l). Mucoid intimal proliferation was present in all the
      sections but FN was seen in 29 (76%). Glomerulosclerosis was present in all the
      sections, and was axially distributed in 7 (18%), segmentally in 22 (58%), and
      globally in 9 (24%). Median 24-hour proteinuria was 2.8 g (0.8-3.5 g IQ range),
      5.6 g (1.7-8.1 g) and 3.4 g (2.6-4.0 g) respectively, and corresponding values of
      serum creatinine were 770 mumol/l (106-1,274 mumol/l IQ range), 522 mumol/l (248
      991 mumol/l) and 1,230 mumol/l (920-1,558 mumol/l) respectively. CONCLUSION: The
      distribution of glomerulosclerosis did not appear to relate to proteinuria or
      serum creatinine, although cases with segmentally distributed glomerulosclerosis
      appeared to have the highest proteinuria, and those with global
      glomerulosclerosis appeared to have the highest serum creatinine levels. FSG
      therefore occurs prominently in primary MHT and may contribute to renal
      dysfunction.

PMID- 12056364
TI  - Uricult trio as a screening test for bacteriuria in pregnancy.
AB  - OBJECTIVE: To establish the effectiveness in an indigent urban population of
      Uricult Trio as a screening test for asymptomatic bacteriuria in pregnancy and in
      diagnosing urinary tract infections (UTI) in symptomatic pregnant women.
      Likelihood ratios were established for positive and negative Uricult Trio test
      results. SUBJECTS: Two populations of patients from the Pretoria region were
      involved: (i) asymptomatic pregnant women attending the antenatal clinic for the
      first time or presenting in labour; and (ii) pregnant women with symptoms
      suggestive of UTI. METHOD: A midstream urine specimen was collected from the two
      populations of patients, plated onto the Uricult Trio and sent to the laboratory
      for culture. RESULTS: The prevalence of asymptomatic bacteriuria in this
      population was 23%, and for women with symptoms suggestive of UTI, 29%. The
      likelihood ratios for a positive test were 1.8 and 1.5 for asymptomatic and
      symptomatic patients respectively. The likelihood ratios for a negative test were
      0.35 and 0.44 for asymptomatic and symptomatic patients respectively. Escherichia
      coli was the causative agent in 36% of cases. CONCLUSION: Uricult Trio is not
      effective as a screening test for asymptomatic bacteriuria in pregnancy or for
      diagnosing UTIs in women with symptoms suggestive of infection.

PMID- 12056365
TI  - Prostaglandin E2 is raised in kwashiorkor.
AB  - OBJECTIVE: Infection is a common occurrence in children with kwashiorkor. It has
      been suggested that infection in kwashiorkor results from immune depression, and
      that the immune depression of kwashiorkor is caused by a diet-associated
      elevation of prostaglandin E2 (PGE2). The purpose of this study was to determine
      whether levels of PGE2 are abnormal in children with kwashiorkor. SETTING AND
      SUBJECTS: Plasma PGE2 and plasma proteins were measured in children admitted with
      oedematous kwashiorkor, and compared with PGE2 in children with cerebral palsy.
      RESULTS: Plasma PGE2 was higher in children with kwashiorkor than in control
      children (7.25 +/- 3.5 v. 3.51 +/- 1.59, P < 0.01). Within the kwashiorkor study
      group there was a significant negative correlation between log-transformed serum
      PGE2 and total plasma protein (r = -0.59, P < 0.001), plasma albumin (r = -0.63,
      P < 0.001), weight-for-age (r = -0.37, P < 0.05), and height-for-age (r = -0.37,
      P < 0.05). The difference in mean values of PGE2 in children with kwashiorkor who
      recovered from the illness and those who died was not significant (7.1 +/- 2.6 v.
      9.1 +/- 4.8, P = 0.36). CONCLUSION: Significantly higher PGE2 levels in children
      with kwashiorkor provide adequate reason for the depression of immune function
      known to occur in these children. Elevated PGE2 levels may also be implicated in
      other components of the illness.

PMID- 12056366
TI  - Patient injury and liability: why worry?

PMID- 12056367
TI  - Slouching toward managed care liability: reflections on doctrinal boundaries,
      paradigm shifts, and incremental reform.

PMID- 12056368
TI  - The role of the courts in shaping health policy: an empirical analysis.

PMID- 12056369
TI  - Managing care in the new era of "systems-think": the implications for managed
      care organizational liability and patient safety.

PMID- 12056370
TI  - Quality control, enterprise liability, and disintermediation in managed care.

PMID- 12056371
TI  - The brave new world of medical standards of care.

PMID- 12056372
TI  - Tort claims analysis in the Veterans Health Administration for quality
      improvement.

PMID- 12056373
TI  - The adverse event of unaddressed medical error: identifying and filling the holes
      in the health-care and legal systems.

PMID- 12056374
TI  - Paths to reducing medical injury: professional liability and discipline vs.
      patient safety--and the need for a third way.

PMID- 12056375
TI  - The problem of medical misadventures: a review of E. Haavi Morreim's Holding
      Health Care Accountable.

PMID- 12056376
TI  - The new federal health privacy regulations: how will states take the lead?

PMID- 12056377
TI  - The artificial heart: how close are we, and do we want to get there?
AB  - The artificial heart appears here to stay, and it will become ever more reliable
      and therapeutic. In the new age of medicine, the attributes of humanity are
      blended with the mechanical and artificial. While we express our humanness by
      seeking new and more creative treatments for illness and delaying death, we are
      inevitably modifying what it means to be human. Ethical issues arise from the
      interface of the physician-patient relationship and the technologies being
      developed in today's laboratories. The new Luddites may well be too fearful to
      tackle the challenges of technology wed to humanity. But they rightly say we seem
      woefully unprepared to deal with human hubris and will to power.

PMID- 12056378
TI  - ADA: U.S. Supreme Court to address whether carpel tunnel constitutes a
      disability.

PMID- 12056379
TI  - ADA: PGA tour must accommodate qualified, disabled golfer.

PMID- 12056381
TI  - Pain: no medical necessity defense for marijuana to controlled substances act.

PMID- 12056382
TI  - Evidence: no medical peer review privilege in discrimination actions.

PMID- 12056380
TI  - Pharmaceuticals: rebate program limited to individuals covered by Medicaid.

PMID- 12056383
TI  - Labor law: no minimum wage for nurses' off-premises, on-call hours.

PMID- 12056384
TI  - [Secondary retention of permanent molars. II. Therapy].
AB  - The efficacy of 5 treatment modalities for secondary retention of permanent
      molars was evaluated in 62 patients with 92 affected molars. The results showed
      that a prosthetic build up is a proper treatment if secondary retention develops
      late in or after the growth spurt. In these cases the extent of infraocclusion is
      slight and relatively stable. If secondary retention starts before the growth
      spurt, immediate removal of the retained molar followed by orthodontic treatment
      to close the diastema gives maximal success. When secondary retention develops
      during the growth spurt, the tooth affected has to be observed at six monthly
      intervals. In such cases, no active treatment is indicated if the extent of
      infraocclusion is minor and stable. In all other cases the affected molar should
      be removed, followed by orthodontic closure of the diastema.

PMID- 12056385
TI  - [Methods and suitability of treatment for dental anxiety].
AB  - 211 Patients followed a special dental fear programme. The Tell-Show-Do Method
      was the method most often used. Half a year after having finished the programme
      all patients received a questionnaire. A majority (74%) of the 158 patients that
      returned the questionnaire reported a good contact with their home dentist.

PMID- 12056386
TI  - [Reminder notices for patients].
AB  - Over 88% of Dutch dentists conduct recall activities. Most frequently dentists
      use a postcard reminder or arrange check-up appointments at the end of a course
      of treatment. Further research is required to elucidate the effectiveness of
      these strategies.

PMID- 12056387
TI  - [Reaction to, "Patient care and ethics. The question of full extraction].

PMID- 12056388
TI  - Health care should be more 'transparent'.

PMID- 12056389
TI  - Fluid movement.

PMID- 12056390
TI  - Back in control. Interview by Mary Hampshire.

PMID- 12056391
TI  - Approaches to improving outcome in stable angina.
AB  - Stable angina is a painful and debilitating disease that requires regular
      monitoring. The National Service Framework for Coronary Heart Disease provides
      the opportunity for nurses to help improve the management of this common chronic
      disease.

PMID- 12056392
TI  - Recognising examples of congenital heart disease.
AB  - With improved treatments now available, many children with congenital heart
      disease are living into adulthood. Increasingly, it is more important for the
      nursing team to be familiar with the more common conditions that may be
      encountered.

PMID- 12056394
TI  - Defining short- and long-term travel.

PMID- 12056395
TI  - Body of knowledge for the practice of travel medicine.

PMID- 12056396
TI  - Bibliography. Current world literature. Molecular genetics.

PMID- 12056397
TI  - Bibliography. Current world literature. Cardiac failure.

PMID- 12056398
TI  - Bibliography. Current world literature. Pediatrics.

PMID- 12056399
TI  - Bibliography. Current world literature. Pathogenesis and immune response.

PMID- 12056400
TI  - Bibliography. Current world literature. Paediatric and neonatal infections.

PMID- 12056401
TI  - Home tension. GAO report leads home health industry to cry foul.

PMID- 12056402
TI  - President's message. Coping.

PMID- 12056403
TI  - CNAs, NACNs, and the tipping point.

PMID- 12056404
TI  - [Urinary tract infections and autoimmune diseases].

PMID- 12056405
TI  - A single nucleotide polymorphism at the splice donor site of the human MYH base
      excision repair genes results in reduced translation efficiency of its
      transcripts.
AB  - BACKGROUND: Adenine paired with 8-hydroxyguanine, a major oxidatively damaged DNA
      lesion, is excised by mutY homologue (MYH) base excision repair protein in human
      cells. Since genetic polymorphisms of DNA repair genes associated with the
      activities and the expression levels of their products may modulate cancer
      susceptibility of individuals, we investigated the effect of a single nucleotide
      polymorphism (SNP) in the MYH gene on the difference in the expression levels of
      its products. RESULTS: An aberrant size of the beta type nuclear form transcript
      was detected in a lung cancer cell line, VMRC-LCD, by reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis. The transcript contained the intron
      1 sequence, and it was due to alternative splicing resulting from IVS1+5G/C SNP.
      The presence of the upstream open reading frame (ORF) on the 5'-side of the
      native ORF in the beta type transcript from the IVS1+5C allele could reduce the
      translation efficiency of the transcript into the nuclear form protein. Thus,
      expression vectors bearing the 5'-untranslated region sequence of either the
      IVS1+5G or 5C allele were constructed. In vitro translation analysis, as well as
      Western blot and quantitative RT-PCR analyses of the H1299 lung cancer cell line
      transfected with these vectors, revealed that the translation efficiency of the
      IVS1+5C transcript into MYH protein was much lower (approximately 30) than that
      of the IVS1+5G transcript. CONCLUSIONS: The SNP at the splice donor site of the
      MYH gene resulted in reduced translation efficiency of its transcripts. This is
      the fourth case of single nucleotide variations that cause alterations in
      translation initiation sites and translation efficiencies in human cells.

PMID- 12056406
TI  - Should measurement of maximum urinary flow rate and residual urine volume be a
      part of a "minimal care" assessment programme in female incontinence?
AB  - OBJECTIVE: The aim of this study was to evaluate the value of routine
      measurements of urinary flow rate and residual urine volume as a part of a
      "minimal care" assessment programme for women with urinary incontinence in
      detecting clinical significant bladder emptying problems. MATERIAL AND METHODS:
      Four hundred and eight women were examined and treated in an open-access,
      interdisciplinary incontinence clinic. A standardized programme for investigation
      and primarily non-surgical treatment of incontinence was applied. RESULTS: Of the
      408 women 43% reported subjectively incomplete bladder emptying. Twenty-six per
      cent had a maximum flow rate less than 15 ml/s, but only 4% at a voided volume >
      or =200 ml. Residual urine more than 149 ml was found in 6%. Two women had
      chronic retention with overflow incontinence. Both had typical symptoms with
      continuous leakage, stranguria and chronic cystitis. Another woman had an
      urethral stricture with massive bladder emptying symptoms. In the remaining 172
      women with symptoms suggesting bladder emptying problems, all but 3 were managed
      by triple voiding and timed micturition. In these 3 patients, who also had
      chronic cystitis, the treatment was supplemented with clean intermittent self
      catheterization. CONCLUSION: The few women (6 (1.5%)) in whom measurements of
      urinary flow rate and residual urine volume had a clinical therapeutic
      consequence, cannot justify these measurements to be routine in a "minimal care"
      programme for assessment of primary, uncomplicated female urinary incontinence.
      Thus, primary health care providers can assess women based on simple guidelines
      without expensive equipment for assessment of urine flow rate and residual urine.

PMID- 12056407
TI  - Starting a home hemodialysis program: single center experiences.
AB  - OBJECTIVES: Home hemodialysis (HHD) has been used only in a minority of patients
      over past years although it may offer significant advantages over the other renal
      replacement therapies. This study describes the systems for and the initial
      results of starting a HHD program. MATERIAL AND METHODS: A program for HHD was
      instituted at a university hospital having more than 20 years of experience in
      training patients for self-care hemodialysis. A working group designed the
      patient and partner education program, installations, water quality assurance,
      logistics, and control systems. RESULTS: Between May 1998 and May 2001, 37
      patients with a mean age of 48.3 +/- 12.5 (24-71) years were trained for HHD (1.0
      patient/month) the mean training time being 2.0 +/- 0.6 (1-3) months. Four
      patients had no helper at home. The dialysis schedules (timing, frequency,
      duration) were individualized at home 41% of the patients having more frequent
      and/or longer treatments (including long-slow night and daily short HHD). The
      weekly dialysis time increased from 13.9 +/- 1.5 (CI 13.4-14.4) initially to 15.5
      +/- 3.7 (CI 14.2-16.7) h (p = 0.008) at the end of follow-up. Significantly (p <
      0.05) increased serum creatinine concentration was observed during the follow-up
      suggesting for an increased muscle mass. Initially 32% and at the end of follow
      up 60% of the patients required no antihypertensive drugs (p < 0.05). Seventeen
      of the 21 drop-outs were caused by renal transplantation and the most common
      causes necessitating hospital back-up were related to vascular access.
      CONCLUSIONS: In conclusion the HHD program started in a unit having experience on
      and commitment for training self-care hemodialysis enabled individualization of
      the dialysis schedules resulting in the institution of long-slow (night) and
      alternate day as well as daily HHD therapies. It improved the control of
      hypertension renal transplantation being the single most common cause of drop
      out.

PMID- 12056408
TI  - Ernest Goodpasture and glomerulonephritis.

PMID- 12056409
TI  - Frontal headaches and an abnormal chest x-ray.

PMID- 12056410
TI  - Bibliography. Current world literature. Outcome measures.

PMID- 12056411
TI  - Bibliography. Current world literature. Food allergy.

PMID- 12056412
TI  - Overexpression of the AtmybL2 gene represses trichome development in Arabidopsis.
AB  - Leaf trichome formation is known to be regulated by the TTG, GL1, GL2, and GL3
      genes in Arabidopsis. GL1 and GL3 encode proteins with Myb and bHLH domains,
      respectively. Overexpression of the AtmybL2 gene, which encodes a single Myb-like
      DNA-binding domain, repressed trichome development in transgenic Arabidopsis
      plants. The amount of GL2 transcription was clearly reduced in the transgenic
      plants. Consistent with this, overexpression of AtmybL2 decreased beta
      glucuronidase (GUS) activity in transgenic plants carrying a GUS-reporter gene
      regulated by the GL2 promoter. These findings, together with the results from our
      yeast two-hybrid analysis, suggest that GL3 gene function and overexpression of
      AtmybL2 act synergistically to inhibit trichome formation by negatively
      regulating GL2 expression.

PMID- 12056413
TI  - Genome-wide profiling of gene expression in 29 normal human tissues with a cDNA
      microarray.
AB  - We have performed a comprehensive analysis of the expression profiles in 25 adult
      and 4 fetal human tissues by means of a cDNA microarray consisting of 23,040
      human genes. This study revealed a number of genes that were expressed
      specifically in each of those tissues. Among the 29 tissues examined, 4,080 genes
      were highly expressed (at least a five-fold expression ratio) in one or only a
      few tissues and 1,163 of those were expressed exclusively (more than a ten-fold
      higher expression ratio) in a particular tissue. Expression of some of the genes
      in the latter category was confirmed by northern analysis. A hierarchical
      clustering analysis of gene-expression profiles in nerve tissues (adult brain,
      fetal brain, and spinal cord), lymphoid tissues (bone marrow, thymus, spleen, and
      lymph node), muscle tissues (heart and skeletal muscle), or adipose tissues
      (mesenteric adipose and mammary gland) identified a set of genes that were
      commonly expressed among related tissues. These data should provide useful
      information for medical research, especially for efforts to identify tissue
      specific molecules as potential targets of novel drugs to treat human diseases.

PMID- 12056415
TI  - Accuracy of genotyping for single nucleotide polymorphisms by a microarray-based
      single nucleotide polymorphism typing method involving hybridization of short
      allele-specific oligonucleotides.
AB  - Advances in technologies for identifying genetic polymorphisms rapidly and
      accurately will dramatically accelerate the discovery of disease-related genes.
      Among a variety of newly described methods for rapid typing of single-nucleotide
      polymorphisms (SNPs), gene detection using DNA microarrays is gradually achieving
      widespread use. This method involves the use of short (11- to 13-mer) allele
      specific oligonucleotides. This method allows simultaneous analysis of many SNPs
      in DNAs from a large number of individuals, in a single experiment. In this work,
      we evaluated the accuracy of a new microarray-based short allele-specific
      oligonucleotide (ASO) hybridization method. There is a 96-well formatted array on
      a single plate, in which up to 256 spots are included in each well. Fluorescent
      probes for our experiments were produced by multiplex PCR amplification often
      target SNP-containing regions. We genotyped 192 individuals across a panel of ten
      single base variations, which included an insertion/deletion polymorphism. For
      comparison, we genotyped the same individuals for the same SNPs by the method of
      single-base extension with fluorescence detection. The typing accuracies of the
      microarray-based PCR-ASO and single-base extension methods were calculated as
      99.9% and 99.1%, respectively, on the basis of genotyping results determined by
      direct sequencing. We conclude that the microarray-based hybridization method
      using short ASO probes represents a potential breakthrough technology for typing
      large numbers of SNPs rapidly and efficiently.

PMID- 12056414
TI  - Characterization of size-fractionated cDNA libraries generated by the in vitro
      recombination-assisted method.
AB  - We here modified a previously reported method for the construction of cDNA
      libraries by employing an in vitro recombination reaction to make it more
      suitable for comprehensive cDNA analysis. For the evaluation of the modified
      method, sets of size-selected cDNA libraries of four different mouse tissues and
      human brain were constructed and characterized. Clustering analysis of the 3' end
      sequence data of the mouse cDNA libraries indicated that each of the size
      fractionated libraries was complex enough for comprehensive cDNA analysis and
      that the occurrence rates of unidentified cDNAs varied considerably depending on
      their size and on the tissue source. In addition, the end sequence data of human
      brain cDNAs thus generated showed that this method decreased the occurrence rates
      of chimeric clones by more than fivefold compared to conventional ligation
      assisted methods when the cDNAs were larger than 5 kb. To further evaluate this
      method, we entirely sequenced 13 human unidentified cDNAs, named KIAA1990
      KIAA2002, and characterized them in terms of the predicted protein sequences and
      their expression profiles. Taking all these results together, we here conclude
      that this new method for the construction of size-fractionated cDNA libraries
      makes it possible to analyze cDNAs efficiently and comprehensively.

PMID- 12056416
TI  - Structural analysis of a Lotus japonicus genome. II. Sequence features and
      mapping of sixty-five TAC clones which cover the 6.5-mb regions of the genome.
AB  - Sixty-five TAC (transformation-competent artificial chromosomes) clones were
      selected from a genomic library of Lotus japonicus accession MG-20 based on the
      sequence information of expressed sequences tags (ESTs), cDNA and gene
      information, and their nucleotide sequences were determined. The average insert
      size of the TAC clone was approximately 100 kb, and the total length of the
      sequenced regions in this study is 6,556,100 bp. Together with the nucleotide
      sequences of 56 TAC clones previously reported, the regions sequenced so far
      total 12,029,295 bp. By comparison with the sequences in protein and EST
      databases and by analysis with computer programs for gene modeling, a total of
      711 potential protein-encoding genes with known or predicted functions, 239 gene
      segments and 90 pseudogenes were identified in the newly sequenced regions. The
      average gene density assigned so far was 1 gene/9140 bp. The average length of
      the assigned genes was 2.6 kb, which is considerably larger than that assigned in
      the Arabidopsis thaliana genome (1.9 kb for 6451 genes). Introns were identified
      in approximately 73% of the potential genes, and the average number and length of
      the introns per gene were 3.4 and 377 bp, respectively. Simple sequence repeat
      length polymorphism (SSLP) or derived cleaved amplified polymorphic sequence
      (dCAPS) markers were generated based on the nucleotide sequences of the genomic
      clones obtained, and each clone was mapped onto the linkage map using the F2
      mapping population derived from a cross of two accessions of L. japonicus, Gifu B
      129 and Miyakojima MG-20. The sequence data, gene information and mapping
      information are available through the World Wide Web at
      http://www.kazusa.or.jp/lotus/.

PMID- 12056417
TI  - Part 35 published, effective October 24.

PMID- 12056418
TI  - NRC NUREG-1556 volume 9 workshop.

PMID- 12056419
TI  - [The role of female veterinarians in Africa].
AB  - While the number of female veterinary students has reached figures as over 80% in
      the Netherlands and other European countries, the number of female veterinary
      students in Africa is also changing but still at a slower pace. Still nowadays,
      according to UNICEF, two-thirds of primary school age children, denied their
      right to basic education, are girls. In addition, especially in rural areas in
      Africa, there are only few secondary schools, so that children, either have to
      travel over large distances on a daily basis or have to live away from their
      families. As girls, already from an early age play an important role in the daily
      household routine, they are often not allowed to leave for schooling. There used
      to be less than 10 veterinary faculties in Africa during the first half of the
      20th century. These faculties were located in South Africa, Sudan, Egypt and
      Nigeria. For many years, African veterinarians were also trained in western
      countries (UK, France, USA) or in former communist countries (Russia, Ukraine,
      Romania, Hungary Eastern Germany, Cuba) depending on the existence of historic or
      political links. A long stay abroad made it more difficult for female students,
      especially for those with children. Still nowadays, female veterinarians in
      Africa are mostly working for the veterinary departments mainly in the urban
      areas. Another area where many female veterinarians can be found are governmental
      diagnostic and research laboratories as well as training institutions such as
      veterinary faculties or agricultural colleges. Generally the salaries at these
      institutions are very low and therefore their male colleagues have gradually
      shifted to work in the private sector with more competitive salaries (private
      clinics, sector pharmaceutical companies, development projects, (agricultural)
      banks, etc). As still in most societies, women tend to follow their husbands,
      most female veterinarians are bound to find employment where their husbands are
      based. In addition, as most postgraduate training required a prolonged stay
      abroad, women encountered difficulties in leaving their families behind to
      improve their career perspectives. Gradually, there has been an increase of
      possibilities of post-graduate training in the African region as well as the
      introduction of a modular system and perspectives for training over the internet.
      These developments will clearly be beneficial for women, as it will enable them
      to follow post-graduate training without leaving their families for extended
      periods. Gradually, also female veterinarians in Africa are becoming empowered
      and recognise their capabilities. The understanding of the importance of gender
      aspects especially with regard to animal husbandry practices has opened up new
      opportunities for female veterinarians to work in extension services and as
      health promoters. The access to further education is the key to expanding their
      professional perspectives.

PMID- 12056420
TI  - Soviet experiments aimed at investigating the influence of space flight factors
      on the physiology of animals and man.
AB  - Results are given of biological experiments on space ship-satellites II, III, IV
      and V, and of scientific investigations made during the flights of Cosmonauts
      Gagarin and Titov aboard space ships Vostok I and Vostok II. Physiological
      reactions to the action of the flight stress-factors are not of a pathological
      character. In the post-flight period no alterations in health conditions of
      either cosmonauts or animals were observed. At the same time some peculiarities
      which were revealed while analyzing physiological reactions and a number of
      biological indices require further investigations. The most important tasks
      remaining are to study the influence of protracted weightlessness, of the
      biological action of space radiation, of the action of acceleration stresses
      after prolonged stay under zero-gravity conditions and also to analyze the
      influence on the organism of the whole combination of spaceflight factors,
      including emotional strain. In the Soviet Union, a great number of biological
      experiments have been conducted with a view to elucidating the action of space
      flight factors on living organisms and the design of systems necessary to ensure
      healthy activity during flight aboard rocket space vehicles. The first flight
      experiments with animals were conducted by means of geophysical rockets. The next
      step in this direction was made by the launching of Sputnik II in 1957 and by
      experiments on space ship-satellites in 1960-61. The main purpose of flight and
      laboratory investigations was to obtain the objective scientific criteria
      essential for ensuring the safety of manned space flight.

PMID- 12056421
TI  - Preparation and results of a 24-hour orbital flight.
AB  - The space age presents man with unprecedented opportunities for discovery and for
      cooperative endeavors to benefit all mankind. My flight of August 6-7, 1961 was
      conducted for the purpose of determining whether man can stay and work
      effectively and whether all systems of the spaceship can operate successfully
      during a period of 24 hours in space. The flight of Vostok II represents an
      experimental step in a logical sequence which included the first earth orbiting
      flight of USSR citizen Yuri A. Gagarin. Preparation for the flight included the
      study of theoretical and applied subjects, testing in various kinds of apparatus
      which provide acceleration, heat and isolation experience, brief airborne
      weightless flights and parachute landings, in addition to extensive training in a
      real spacecraft having simulators for normal and emergency contingencies of space
      flight. The actual flight was therefore carried out with a sense of confidence
      and familiarity and with continuous close radio contact with ground centers from
      whom my fellow cosmonauts served as spokesmen. Sequential boosters totaling 600
      000 kg thrust placed the 4731 kg spaceship into a perfect orbit varying in
      altitude from 178-246 km in a plane 64 degrees 58' inclined to the equator. The
      spaceship made 17 orbits around the earth landing 25 hours, 18 minutes after take
      off. The cabin had full atmospheric pressure and a comfortable habitability which
      could be extended for 10 days. I was able to maneuver the spaceship and perform
      many other control functions, make observations and take pictures of the earth
      and its cloud cover, eat meals and sleep all with good efficiency. I experienced
      mild symptoms suggestive of seasickness which were aggravated by head turning,
      ameliorated by sleep and entirely relieved by resumption of g-loading during
      descent. Altogether analyses of the physical and structural performance of the
      spaceship and the continuously monitored physiological responses of the pilot
      indicate that all systems operated with high reliability and according to our
      scientific expectations.

PMID- 12056422
TI  - United States experience on the utilization of man's capabilities in a space
      environment.
AB  - This paper concerns the stresses on the flight crew in various phases of space
      flight missions and the ability of the crew to perform piloting-type tasks as
      well as other specific operations in the presence of these stresses. The mission
      phases include powered flight, free flight, space maneuvers, atmospheric entry,
      terminal phase, and surface operation. The stresses of the space environment are
      caused by forces and or motions or lack thereof, the space environment itself,
      the nature of the environment within the spacecraft, and the mental and physical
      demands on the flight crew. Among crew functions are control of the onboard
      systems, navigation and guidance of the spacecraft, maintenance and emergency
      operation, communications, and the conduct of scientific experiments. The paper
      draws on information obtained from the flight research to date as well as from
      ground tests and analyses. From the results one can conclude that man can very
      ably withstand the stresses of short duration missions into near space and has
      demonstrated ability to perform the type of tasks associated with flight crew
      operation. The chief unknown factors of future flight operations are the stresses
      produced by longer duration missions. Consideration of the problems involved
      leads to the conclusion that they are amenable to engineering solution at some
      expense to spacecraft weight and performance. It appears desirable therefore to
      utilize the flight crew to a high degree in future missions in the type of tasks
      where human judgment is needed or where significant simplification of on-board
      equipment may result.

PMID- 12056423
TI  - Summary results of the first United States manned orbital space flight.
AB  - This paper describes the principal findings of the first United States manned
      orbital space flight in light of the flight mission. Consideration is given to
      the coordinated tracking network, recovery forces and to the spacecraft and its
      several functional systems. These include mechanisms for heat protection, escape
      maneuvers, spacecraft control, power supply, communications, life support and
      landing. A few difficulties encountered in the flight and deviations from the
      planned sequence are described. Craft preparation, aeromedical studies, flight
      plan and particularly flight observations--including the color, light, horizon
      visibility by day and by night, cloud formations and sunrise and sunset effects
      are given in some detail. The general conclusion from the MA-6 flight is that man
      can adapt well to new conditions encountered in space flight and that man can
      contribute importantly to mission reliability and toward mission achievement
      through his capacities to control the spacecraft and its multiple systems
      contribute to decision making and adaptation of programming as well as to direct
      exploratory and experimental observations.

PMID- 12056424
TI  - Significance of vestibular organs in problems of weightlessness.
AB  - Two important questions concerning the organs of equilibrium are posed by orbital
      and space flights. The first is whether exposure to weightlessness may evoke
      symptoms of vestibular origin, and the second is how to prevent symptoms of
      vestibular origin should it be decided to abolish weightlessness by causing the
      spacecraft to spin. It is important to determine whether vestibular symptoms are
      to be ascribed to the otolith apparatus or to the semicircular canals, or to
      both. During exposure to weightlessness the usual gravitational stimulus to the
      otolith apparatus is lost, and this reduction in afferent input might be expected
      to disturb the integrative patterns in the central nervous system. All such
      disturbances are special instances of a common cause for the appearance of
      functional syndromes such as seasickness. If orbiting vehicles are caused to
      rotate in order to abolish weightlessness, the angular velocity will be
      determined by the effective radius of rotation and the rate of spin, i.e., how
      nearly it is desired to simulate 1 g. At very short radii the complicating
      effects of exposure of the body to variations in centripetal force must be
      considered. With longer radii the principal stress will arise as a result of
      constant rotation, which, in combination with head movements, generates Coriolis
      forces. These forces cause bizarre patterns of stimulation of the semicircular
      canals which in turn may result in illusions and "canal sickness". This type of
      motion sickness has its origin in the semicircular canals and deserves the term
      "canal sickness". The angular velocities which represent a negligible stress or a
      tolerable stress are defined. A brief description is given of illusory phenomena
      and other manifestations together with the time-course of the adaptive process.

PMID- 12056425
TI  - Perspectives for the development of exobiology.
AB  - In the majority of the papers dealing with the status and prospects of the
      development of exobiology a theoretical analysis predominates. More attention
      should be given to the discussion of methods and experiments carried out at the
      present time or planned for the near future. In investigating life in the cosmos,
      we attach considerable interest to detection of compounds specific to living
      beings, in particular, organic compounds of phosphorus, porphyrins, amino
      nitrogen and others. In searching for microorganisms on other planets and in
      interplanetary space the greatest danger is that, as a result of errors in
      technique, the investigator will detect earthly microorganisms which have invaded
      and reproduced in the nutrient mediums used. Information on the vitality of
      microbes detected in the ground taken in the zone of eternal frigidity, in big
      pieces of rock salt, in meteorites, etc. confirms these apprehensions. Initially,
      search for heterotrophic bacteria should be carried out, then for phototrophic,
      denitrifying, sulfate-reducing, nitrogen-fixing microorganisms, as well as
      bacteria oxydizing sulfur, iron, methane and hydrogen. Instruments for detection
      of cosmobionts can be based on nephelometry, potentiometry, manometry and on the
      use of carbon labelled compounds and added to the nutrient medium. Investigations
      elucidating the influence of low and high temperatures, vacuum, and radiation on
      living cells are possible to carry out on earth and therefore are most accessible
      to exobiology. They give interesting results and in some degree make it possible
      to approach the study of the conditions to which life would be exposed in space.
      The sterilization of space ships is of paramount importance for further
      exobiological investigations. Under space conditions microbes will not completely
      perish on the space ship surface and, therefore, careful sterilization is
      necessary. The assertion that earth microbes, having reached the lunar surface,
      will not be able to develop is not free of objections. To carry out sterilization
      so that space ships will not contain dead bodies of microbes is impossible.
      Therefore, the wish expressed sometimes that "carcasses" of microbes should not
      be conveyed onto other planets is practically unrealizable.

PMID- 12056426
TI  - [Contribution to the study of the effects of weightlessness on the central
      nervous system of the rat].
AB  - We have studied the effects of various states of acceleration on the
      physiological activity of white rats. Initial experimental trials were carried
      out in the course of a flight of the Veronique missile. In another series of
      experiments the trials took place in an airplane in the course of successive
      parabolic flights at several minutes intervals producing periods of
      weightlessness of 33 to 44 seconds. We recorded the electrical activity of a
      large area lying between one electrode located in the somesthesic area and
      another electrode located in the homolateral visual area. In addition, cardiac
      and respiratory rate and electrical activity of the mesencephalic reticular
      formation and of the muscles of the neck were recorded. We found an intense
      cortical activation during the entire duration of the missile flight. In the
      airplane during the periods of weightlessness basic electrical activity has not
      been modified. Recordings of electrical activity in the mesencephalic reticular
      formation do not show any modification during missile flight. Afterwards appeared
      a flattening with the reduction of frequency. In the course of periods of
      weightlessness in airplane flight we have observed no modification of background
      electrical activity. Recording of neck muscle potentials shows, during
      weightlessness in airplane flight, a distinct augmentation of background tone.
      These findings seem in favor of a facilitation of reticular origin as a result of
      the abrupt diminution of volume of sensory information following the
      disappearance of the stimulus of gravity.

PMID- 12056427
TI  - The biological effects of heavy cosmic ray particles.
AB  - There has been rather extensive biological experience with most of the radiations
      known to exist in space beyond the earth's atmosphere, with the exception of the
      very high energy heavy particles which form a small part of the galactic cosmic
      rays. These particles cannot be reproduced in the laboratory, but from
      experiments with smaller particles, and from theoretical considerations, there
      was reason to fear they might be very damaging biologically. A very narrow beam
      of 22 MeV deuterons has been developed which will have the same biological effect
      as the track of a very heavily ionizing particle. Using this microbeam the
      following results have been obtained on mice: (1) brain tissue is very
      insensitive to this type of radiation, (2) this radiation will cause minute
      abnormalities in the lens of the eye but in general these do not progress to form
      cataracts; but if they do, they remain extremely small, (3) if a hair follicle is
      hit, the hair from that follicle will turn grey. It is concluded that the heavy
      cosmic ray particles do not pose a serious problem for manned space flight.

PMID- 12056428
TI  - Estimates of radiation doses in space on the basis of current data.
AB  - A gross survey of data on Van Allen belt radiations, galactic cosmic radiation,
      and solar cosmic radiation is presented. On the basis of these data that are, in
      part, fragmentary and uncertain, upper and lower limits of rad doses under
      different amounts of mass shielding are estimated. The estimates are preliminary
      especially in the cases of chance encounter with solar flare protons. Generally,
      the relative biological effectiveness of the high energetic space radiations and
      their secondaries appear insufficiently known to give detailed biological or rem
      doses. The overall ionization dosage of the low level galactic cosmic radiation
      in free space is estimated to be even in solar minimum years equivalent to less
      than 50 rem/year or 1 rem/week. Mass shielding up to 80 g/cm2 would not reduce
      the ionization dosage but would shield against heavy primaries and heavy ionizing
      secondaries, thus reducing the biological dose. The flux of energetic protons in
      the maximum intensity zone of the inner Van Allen belt is by about four orders of
      magnitude higher, their energy and penetration power, of course, lower. A shield
      of 25 g/cm2 would reduce the dose rate from 20 rad/hour under 2 g/cm2 to 5
      rad/hour. These proton dose rates and also the electron and X-radiation dose
      rates under some g/cm2 shielding of low z-number material will not constitute a
      radiation hazard for flights straight through the inner and outer belt in about
      two hours. Staying within the maximum of the inner belt for two days would,
      however, lead even within 25 g/cm2 depth of outer shield and body itself to a
      dose of 200 rad which is on the permissible limit. Extreme solar cosmic ray
      events or proton showers of high intensity and a duration of days occurred with a
      frequency of 1-4 per year during the last highly active cycle. For the
      penetrating, most intense high energy event of February 23, 1956, the dose within
      25 g/cm2 is estimated to have been in the order of 50 rad. In most cases the dose
      decreased more rapidly with penetration depth and would have been even in
      multiple events with such high shielding below critical levels, especially on
      inner organs. On the surface of the body and in a lightly shielded space vehicle
      or protected by a space suit only the dose can, especially in multiple events,
      reach values of 1000 rad and more.

PMID- 12056429
TI  - Complete dose analysis of the November 12, 1960 solar cosmic ray event.
AB  - A detailed analysis of the November 12, 1960 solar cosmic ray event is presented
      as an integrated space flux and dose. This event is probably the most interesting
      solar cosmic ray event studied to date. Direct measurements were made of solar
      protons from 10 MeV to 6 GeV. During the double peaked high energy part of the
      event evidence is presented for the trapping of relativistic particles in a
      magnetic cloud. The proton energy spectrum is divided into 3 energy intervals,
      with separate energy power law exponents and time profiles carried through for
      each. The three groups are: (1) (30<E<80 MeV), (2) (80<E<440 MeV), (3) (440 MeV<
      E< 6 GeV). Included in the analysis are the results of rocket measurements which
      determined the spectrum down to 10 MeV twice during the event, balloon results
      from Fort Churchill and Minneapolis, earth satellite measurements, neutron
      monitors in New Hampshire and at both the North and South Pole and riometer
      results from Alaska and Kiruna, Sweden. The results are given in Table 1 [see
      text]. The results of our analyses of other solar cosmic ray events are also
      included with a general discussion of the solar flare hazards in space.

PMID- 12056430
TI  - Life sciences and space research: a session of the Third International Space
      Science Symposium, Washington, D.C., April 30-May 9, 1962.

PMID- 12056431
TI  - Scientist reveals secret of genome: it's his.

PMID- 12056433
TI  - Racial disparity is found in AIDS clinical studies.

PMID- 12056432
TI  - Eyes of Texas fasten on life, death and the premature infant.

PMID- 12056435
TI  - Risking limbs for height, and success, in China.

PMID- 12056436
TI  - A search for justice in our genes.

PMID- 12056437
TI  - Percutaneous vertebroplasty: a bone cement procedure for spinal pain relief.
AB  - Percutaneous vertebroplasty (PV), a procedure where bone cement is injected into
      a partially collapsed vertebral body, is used to relieve pain and provide
      mechanical stability in cases of osteoporosis or tumour infiltration. PV provided
      rapid pain relief and increased mobility in most patients according to the
      results from 15 uncontrolled studies in 882 persons where over 1,500 vertebrae
      were treated. Serious complications from bone cement leaks and adjacent vertebral
      fractures were rare. Despite the increasing use of PV there are no controlled
      prospective studies on safety and efficacy with long-term follow-up. Physician
      and supply costs range from C $300 -600 per vertebra treated. This figure
      excludes hospital or investigational costs.

PMID- 12056438
TI  - Suit says company promoted drug in exam rooms.

PMID- 12056440
TI  - Debate on human cloning turns to patents.

PMID- 12056441
TI  - State will require coverage of treatment for infertility.

PMID- 12056442
TI  - Once-invisible sperm donors get to meet the family.

PMID- 12056443
TI  - States pursue cloning laws as Congress debates.

PMID- 12056444
TI  - The anti-cloning conundrum.

PMID- 12056445
TI  - Desperately seeking kids for clinical trials.

PMID- 12056446
TI  - Designing babies: genetic manipulation has just led to the birth of an
      Alzheimer's-free baby. Is this a step toward a 'Brave New World'? or a needed
      medical advance?

PMID- 12056447
TI  - Case involving tests on newborns shows need for strict ethics.

PMID- 12056448
TI  - Free to be me: would-be cloners pushing the debate.

PMID- 12056450
TI  - Development of porcine embryos produced by IVM/IVF in a medium with or without
      protein supplementation: effects of extracellular glutathione.
AB  - This study was designed to examine the effects of extracellular reduced
      glutathione on development of pig embryos, produced by in vitro maturation (IVM)
      and in vitro fertilisation (IVF), in a chemically defined North Carolina State
      University (NCSU) 23 medium or in NCSU 23 medium with bovine serum albumin (BSA).
      Microfilament distribution, as a marker of embryo quality, was also examined by
      immunocytochemical staining and confocal microscopy. When the inseminated oocytes
      were cultured in the defined medium containing 0-0.5 mM glutathione, blastocyst
      formation as observed only in the media with glutathione (8.5-16.0%). Increased
      numbers of blastomeres were observed in the blastocysts as the concentration of
      glutathione was increased (18.8 +/- 7.2 to 31.0 +/- 8.6). In NCSU 23 medium with
      4 mg BSA/ml, addition of glutathione at concentrations of 0.125-0.5 mM
      significantly increased the proportions of oocytes that developed to blastocysts
      (39.2-52.5%) compared with the control (29.5%). However, no difference was
      observed in the average cell number in the blastocysts (41.9 +/- 15.6 to 49.1 +/-
      15.5). There were no significant differences in the microfilament distribution in
      the embryos produced in the defined medium and in the BSA-containing medium.
      These results indicate that pig embryos produced by IVM/IVF can develop to the
      blastocyst stage in a defined medium. BSA and glutathione have a synergistic
      effect on pig embryo development.

PMID- 12056449
TI  - Detection of glycine receptor/Cl- channel beta subunit transcripts in mouse
      testis.
AB  - The sperm glycine receptor/Cl- channel (GlyR) is important to the initiation of
      the mammalian sperm acrosome reaction by the egg zona pellucida, but its presence
      in spermatogenic cells has not been demonstrated. Reverse transcriptase
      polymerase chain reaction studies confirmed that GlyR beta subunit transcripts
      similar to those of the neuronal GlyR beta subunit are present in the testis of
      Swiss Webster mice. In situ hybridisation analysis demonstrated that GlyR beta
      subunit mRNAs were expressed within the germ cells of seminiferous tubules in
      those mice.

PMID- 12056451
TI  - Male pronuclear formation and sperm mitochondria in porcine oocytes following
      intracytoplasmic injection of pig or mouse sperm.
AB  - In the present study we determined the chromatin organization and fate of
      introduced mitochondria in porcine embryos following intracytoplasmic injection
      of pig or mouse sperm cells. At 3, 6, 9 and 12 h following injection of pig or
      mouse spermatozoa or isolated sperm heads, the oocytes were fixed and stained
      with propidium iodide. Between 3 and 6 h following injection, both porcine and
      murine sperm chromatin developed into pronuclei. The male and female pronuclei
      were apposed within 12 h in porcine oocytes following sperm injection from either
      source. We also introduced foreign mitochondria from either mouse or pig sperm
      midpiece into porcine oocytes following sperm injection. While porcine sperm
      mitochondria rapidly disappeared from the actively developing porcine oocytes,
      mouse sperm mitochondria remained in the embryos until the 8-cell stage. These
      results suggest that pronuclear formation and movement occur between 6 and 12 h
      following sperm incorporation into the cytoplasm, and that foreign mitochondria
      are selectively removed in a species-specific manner.

PMID- 12056452
TI  - Chromatin and microtubule organisation in maturing and pre-activated porcine
      oocytes following intracytoplasmic sperm injection.
AB  - Chromatin and microtubule organisation was determined in maturing and activated
      porcine oocytes following intracytoplasmic sperm injection in order to obtain
      insights into the nature of sperm chromatin decondensation and microtubule
      nucleation activity. Sperm chromatin was slightly decondensed at 8 h following
      injection into germinal vesicle stage oocytes. Sperm-derived microtubules were
      not seen in these oocytes. Following injection into metaphase I (MI)-stage
      oocytes, sperm chromatin went to metaphase in most cases. A meiotic-like spindle
      was seen in the sperm metaphase chromatin. In a few MI-stage oocytes, sperm
      chromatin decondensed at 8 h after injection, and a small sperm aster was seen.
      Sperm injection into oocytes at 5 h following activation failed to yield
      pronuclear formation. Maternally derived microtubules were organised near the
      female chromatin in these oocytes, and seemed to move condensed male chromatin
      closer to the female pronucleus. At 18 h after sperm injection into pre-activated
      oocytes, a condensed sperm nucleus was located in close proximity to the female
      pronucleus. These results suggest that the sperm nuclear decondensing activity
      and microtubule nucleation abilities of the male centrosome are cell cycle
      dependent. In the absence of a functional male centrosome, microtubules of female
      origin take over the role of microtubule nucleation for nuclear movement.

PMID- 12056453
TI  - Immunohistochemical localisation of gp69/64 molecules in Xenopus egg envelopes in
      relation to their sperm binding activity.
AB  - A monoclonal antibody (6964M) was generated against the envelope component
      gp69/64 of Xenopus laevis eggs. On indirect immunofluorescence using this
      antibody, the positive reaction was seen on the surface of both vitelline
      envelope (VE) and coelomic envelope (CE). On immunoelectron microscopy, gp69/64
      was preferentially distributed on the thick bundles forming the edge of the
      tunnel openings on CE, and this distribution pattern was fundamentally inherited
      by VE. Counting the number of immunogold particles indicated that VE has about
      twice as many particles as CE, with a 3-4 times higher density at the animal pole
      than vegetal pole. The number of sperm bound to CE was small, being approximately
      one-twentieth of the number of sperm bound to VE. An extremely small number of
      sperm (< 2 per animal hemisphere) was found to bind to VE* of activated eggs as a
      background. The sperm binding to CE was inhibited by pretreatment of the
      envelopes with 6964M or in the presence of purified gp69/64 from VE on
      insemination, confirming that sperm binding is mediated by gp69/64 exposed on the
      CE surface. In spite of at most a 2-fold increase in the amount of exposed
      gp69/64, the sperm binding increased about 20-fold upon CE-to-VE conversion,
      suggesting that the increase in the amount of exposed gp69/64 is itself
      insufficient to explain the increase in the number of bound sperm.

PMID- 12056454
TI  - Bovine abnormal preimplantation embryos: analysis of segregated cells occurring
      in the subzonal space and/or blastocoele cavity for their nuclear morphology and
      persistence of RNA synthesis.
AB  - Bovine embryos in the early blastocyst/blastocyst stage were analysed by [5
      3H]uridine labelling followed by electron microscopic autoradiography. In normal
      control embryos an intact zona pellucida, evenly developed blastomeres and a
      transparent perivitelline space were seen. In this group, the blastomeres of the
      trophoblast and embryoblast showed high homogeneous labelling localised in the
      nucleoplasm and even more intense labelling in the nucleolus. On the contrary, in
      addition to evident cytoplasmic disintegration, a clearly different labelling
      pattern and a low labelling intensity were observed in the nuclei of the
      segregated cells in the subzonal space and in those free in the blastocoele
      cavity. A typical nuclear morphological feature of these blastomeres was
      chromatin marginalisation, similar to that observed in embryos treated with
      actinomycin D for transcription inhibition. It is concluded that the segregated
      cells are arrested in their further differentiation.

PMID- 12056455
TI  - Births of calves derived from embryos produced by intracytoplasmic sperm
      injection without exogenous oocyte activation.
AB  - Tail-cut bovine spermatozoa were microinjected into ooplasmic lipid polarised, in
      vitro matured bovine oocytes using a piezomicropipette-driving system. No
      exogenous oocyte activation treatment was used. Of the sperm-injected oocytes,
      86.3% were activated, 71.8% cleaved and 22.7% developed to the blastocyst stage.
      The average cell count of the blastocysts was 122.5 +/- 15 and a majority (81.8%)
      of the blastocysts were cytologically normal (diploid). When transferred to
      recipient cows, 5 of 8 blastocysts developed to fetuses and 4 of 7 recipients
      became pregnant. Normal offspring were born.

PMID- 12056456
TI  - In vitro production of cattle-water buffalo (Bos taurus--Bubalus bubalis) hybrid
      embryos.
AB  - Interspecific hybrid embryos are useful models for the study of maternal-fetal
      interactions, transmission pattern of species-specific markers and parental
      contributions to growth and developmental potential of pre-attachment embryos. In
      an attempt to investigate the possibility of producing hybrid embryos of domestic
      cattle (Bos taurus) and water buffalo (Bubalus bubalis), cattle oocytes were
      exposed to buffalo sperm and buffalo oocytes were exposed to cattle sperm and the
      cleavage rate and the post-fertilisation features of hybrid embryos up to the
      blastocyst stage were compared with those of buffalo and cattle embryos. The
      cleavage rate in buffalo oocytes exposed to cattle sperm was low (40.8%), with
      only 8.8% of these hybrid embryos reaching the blastocyst stage. Cattle oocytes
      exposed to buffalo sperm showed 86.3% cleavage, while 25.9% of these attained the
      blastocyst stage. The speed of development of both types of hybrids was
      intermediate between that of cattle and buffalo embryos, with hatching occurring
      on day 7.5 in hybrid embryos, day 8-9 in cattle and day 7 in buffalo. The
      proportions of cells contributing to the trophectoderm and the inner cell mass
      were closer to those of the maternal species in both types of hybrid embryos. Our
      results indicate that cattle-water buffalo hybrid embryos produced using inter
      species gametes are capable of developing to advanced blastocyst stages and that
      their in vitro fate, and developmental potential, are influenced by the origin of
      the oocyte.

PMID- 12056457
TI  - Ultrastructural characteristics of the follicle cell-oocyte interface in the
      oogenesis of Ceratophrys cranwelli.
AB  - In this work we carried out an ultrastructural analysis of the cell interface
      between oocyte and follicle cells during the oogenesis of the amphibian
      Ceratophrys cranwelli, which revealed a complex cell-cell interaction. In the
      early previtellogenic follicles, the plasma membrane of the follicle cells lies
      in close contact with the plasma membrane of the oocyte, with no interface
      between them. In the mid-previtellogenic follicles the follicle cells became more
      active and their cytoplasm has vesicles containing granular material. Their
      apical surface projects cytoplasmic processes (macrovilli) that contact the
      oocyte, forming gap junctions. The oocyte surface begins to develop microvilli.
      At the interface both processes delimit lacunae containing granular material. The
      oocyte surface has endocytic vesicles that incorporate this material, forming
      cortical vesicles that are peripherally arranged. In the late previtellogenic
      follicle the interface contains fibrillar material from which the vitelline
      envelope will originate. During the vitellogenic period, there is an increase in
      the number and length of the micro- and macrovilli, which become regularly
      arranged inside fibrillar tunnels. At this time the oocyte surface exhibits deep
      crypts where the macrovilli enter, thus increasing the follicle cell-oocyte
      junctions. In addition, the oocyte displays coated pits and vesicles evidencing
      an intense endocytic activity. At the interface of the fully grown oocyte the
      fibrillar network of the vitelline envelope can be seen. The compact zone
      contains a fibrillar electron-dense material that fills the spaces previously
      occupied by the now-retracted microvilli. The macrovilli are still in contact
      with the surface of the oocyte, forming gap junctions.

PMID- 12056458
TI  - Genetic expression of monocarboxylate transporters during human and murine oocyte
      maturation and early embryonic development.
AB  - During the early preimplantationes of human embryos, pyruvate and lactate, but
      not glucose, are the preferred energy substrates. Transport of these
      monocarboxylates is mediated, in mammalian cells, by a family of transporters,
      designated as monocarboxylate transporters (MCTs). Human and mouse genetic
      expression of MCT members 1, 2, 3, 4 and basigin, a chaperone protein of MCT1 and
      MCT4, was qualitatively analysed using the reverse transcription nested
      polymerase chain reaction (RT-nested PCR) in immature oocytes (germinal vesicle
      stage; GV), in non-fertilised metaphase II (MII) oocytes and in embryos from 2
      cell stage to blastocysts. Transcripts encoding for MCT1 and MCT2 were present,
      under a polyadenylated form, in the majority of the human and mouse oocytes and
      early embryos. MCT3 transcripts were not detected in either human or mouse. MCT4
      mRNA was not detected in human oocytes and embryos, but was present in mouse
      oocytes and embryos. This fact could imply differences in lactate transport and
      regulation of intracellular pH between human and murine early embryos. Basigin
      transcripts were present in mouse and human MII oocytes and preimplantation
      embryos, but were not detected at GV stage. However, using 3' end-specific
      primers in the RT reaction instead of Oligo(dT)12-18 primers, transcripts
      encoding for this protein were then detected at GV stage in both species. This
      result suggests that a regulated polyadenylation process occurs during oocyte
      maturation for these transcripts. Thus, basigin mRNA can be considered as a
      marker of oocyte cytoplasmic maturation in human and mouse species.

PMID- 12056459
TI  - Identification of distinct K+ channels in mouse spermatogenic cells and sperm.
AB  - Potassium (K+) channels are believed to regulate mammalian sperm acquisition of
      fertilising capacity. However, the molecular identity of these proteins in sperm
      has not been elucidated. In this report, using immunoconfocal and electron
      microscopy we show that a minimum of four different classes of K+ channels
      (Kv1.1, Kv1.2, Kv3.1 and GIRK1) are present and regionally distributed over the
      surface of mouse epididymal sperm. In addition, the use of reverse transcription
      polymerase chain reaction on RNA from mouse spermatogenic cells allowed the
      amplification of multiple transcripts corresponding to the channels identified by
      immunocytochemistry. Consistent with this, whole-cell patch-clamp recordings
      showed the expression of at least two different outwardly rectifying K+ currents
      in spermatogenic cells.

PMID- 12056460
TI  - Progesterone treatment of boar spermatozoa improves male pronuclear formation
      after intracytoplasmic sperm injection into porcine oocytes.
AB  - Boar spermatozoa were prepared for intracytoplasmic sperm injection (ICSI) by two
      different treatments to facilitate sperm chromatin decondensation and improve
      fertilisation rates after ICSI in pigs: spermatozoa were either frozen and thawed
      without cryoprotectants, or treated with progesterone. Morphological changes of
      the sperm heads after the treatments were examined and then the activation of
      oocytes and the transformation of the sperm nucleus following ICSI were assessed.
      After freezing and thawing, the plasma membrane and acrosomal contents over the
      apical region of sperm head were lost in all the spermatozoa. Following treatment
      with 1 mg/ml progesterone, the acrosome reaction was induced in 61% of
      spermatozoa. After injection of three types of spermatozoa, non-treated
      spermatozoa and progesterone-treated (i.e. acrosome-reacted) spermatozoa induced
      oocyte activation, but frozen-thawed spermatozoa induced oocyte activation at a
      significantly lower rate. Sixty-two per cent of sperm heads remained orcein
      negative for 6 h, however, resulting in delayed sperm chromatin decondensation
      and low male pronuclear formation in the oocytes injected with a non-treated
      spermatazoon. Since the treatments of freezing and thawing and progesterone for
      spermatozoa accelerated the initial change in sperm chromatin and the latter
      treatment induced oocyte activation earlier, it is considered that the delay in
      oocyte activation and decondensation of sperm chromatin after injection of non
      treated spermatozoa is caused by the existence of the sperm plasma membrane.
      These results show that progesterone treatment efficiently induces the acrosome
      reaction in boar spermatozoa without destroying their potency for oocyte
      activation, and the induction of the acrosome reaction results in the promotion
      of male pronuclear formation after ICSI.

PMID- 12056461
TI  - Massive intraperitoneal hemorrhage from traumatic intrasplenic pseudoaneurysms:
      treatment using superselective embolotherapy.
AB  - The importance of splenic preservation in the setting of penetrating and blunt
      trauma has led to the development of more sophisticated and noninvasive methods
      for controlling splenic hemorrhage. Although controversy exists, transcatheter
      embolotherapy has challenged the use of splenectomy in patients suffering from
      persistent bleeding after splenic trauma. We describe a case of a 41-year-old man
      with hepatitis C, ethanol-induced liver disease, and portal hypertension who
      presented with splenic rupture secondary to blunt trauma. Continued intra
      abdominal hemorrhage was successfully controlled by superselective embolotherapy
      using microcoils and gelatin sponge pledgets.

PMID- 12056462
TI  - Probability of lymph node metastasis in small gastric cancer tumor: is it an
      indication for limited surgery?
AB  - The purpose of this study was to determine the factors that are predictive of
      lymph node metastasis in a small gastric cancer tumor <2 cm in diameter. The
      clinicopathological features of 17 patients with node-positive small gastric
      cancer were reviewed from the database of gastric cancer at the Department of
      Surgery, Sendai National Hospital, Sendai, Japan, and they were compared with
      those of 131 patients with node-negative cancer. The independent risk factors
      influencing the lymph node metastasis were determined by multiple logistic
      regression analysis. Depth of invasion, macroscopic appearance, cancer-stromal
      relationship, and lymphatic microinvasion were found to be associated with lymph
      node metastasis. The variables found to be significant risk factors for lymph
      node metastasis were depth of invasion (P = 0.0250) and lymphatic microinvasion
      (P = 0.0028). It is possible for even a small gastric cancer tumor to have lymph
      node metastasis. A surgeon treating a small gastric cancer tumor must consider
      that although the cure rate is high, >10% of these tumors have lymph node
      metastases. Because of the possibility of lymph node metastasis, even with
      accurate knowledge of the depth of cancer invasion, selective performance of
      local resection or limited surgery with incomplete lymph node dissection is not
      justified. Accurate preoperative diagnosis and the appropriate decision for
      surgical indication are important. Large-scale randomized, controlled trials
      should be performed to show the advantage of limited surgery for gastric cancer.

PMID- 12056463
TI  - Reversal of steal syndrome following creation of arteriovenous fistula by banding
      with a Gore-Tex cuff: a new technique.
AB  - Steal syndrome, especially in elderly patients with peripheral vascular disease,
      is a serious complication following creation of an arteriovenous fistula (AVF)
      that, if neglected, can lead to amputation. The classic maneuver to deal with the
      steal syndrome is the ligation of the AVF and performance of another procedure to
      gain dialysis access. We describe a simple technique of effectively reversing the
      steal syndrome by banding the vein of the AVF with a ringed Gore-Tex cuff that
      salvages the AVF and allows its immediate use for dialysis.

PMID- 12056465
TI  - Operative management of substernal goiter: analysis of 52 patients.
AB  - Thyroid surgery for substernal goiter is an uncommon operation. This study was
      carried out to evaluate the clinical presentation, workup, surgical
      complications, and risk of malignancy for substernal goiter. From January 1995 to
      June 2001, 52 patients [27 men and 25 women (ratio, 1.1:1); average age of 52
      years (range, 26-71 years)] underwent thyroid surgery for substernal goiter at
      Akdeniz University Hospital. All patients were symptomatic at presentation. A
      chest radiograph was used for most patients with a computed tomography scan being
      by far the most helpful in the study. A cervical approach was adequate for
      resection of the lesions in 50 (96%) patients. Two (4%) patients required medial
      sternotomy for removal of thyroid tissue. There was no perioperative mortality.
      Transient recurrent laryngeal nerve (RLN) palsy occurred in 2 (4%) patients, and
      permanent RLN occurred in 2 (4%) patients. The incidence of transient and
      permanent hypoparathyroidism was 8% and 6%, respectively. Other complications
      included wound infection in 2 (4%) patients and postoperative bleeding in 1
      patient (2%). Histopathologically, 46 (88%) lesions were benign and 6 (12%) were
      malignant. Because the history of substernal goiter is progressive enlargement,
      surgical removal of thyroid tissue is always indicated and should be performed as
      soon as possible, unless there are contraindications for surgery. Cervical collar
      incision is nearly always adequate, with few exceptions.

PMID- 12056464
TI  - Treatment of locally aggressive well-differentiated thyroid cancer.
AB  - The object of this study, conducted at Unicamp between 1988 and 1998, was to
      evaluate retrospectively the outcome of patients treated for locally aggressive
      well-differentiated thyroid carcinomas (LATC). Nineteen (42%) of 45 patients with
      thyroid carcinomas were considered to have LATC. The preoperative diagnosis of
      carcinoma was made either by fine needle aspiration biopsy (15 patients) or
      during surgery (4 patients). The usual prognostic factors were analyzed and
      classified according to risk groups. Survival was evaluated using the Kaplan
      Meier method. Most of the patients were female (73%), with a mean age of 48
      years. Eighteen (95%) had papillary carcinomas. Four patients were classified as
      high risk (21%) and the remaining 15 (79%) as intermediate risk. All patients
      underwent total thyroidectomy and different types of neck dissections. The
      structures invaded by tumors were strap muscles and trachea (four cases);
      recurrent nerve and larynx (three cases); manubrium, esophagus, and jugular vein
      (two cases); and hyoid bone and pharynx (one case). Complete tumor resection was
      carried out according to the extent of local invasion; no postoperative deaths
      resulted. Details of the procedures are provided in Table 4 and in the
      Discussion. Postoperative radioactive iodine treatment was used in 15 patients
      (79%). A mean follow-up (+/-7 years) revealed 13 (68%) patients without disease,
      4 patients (21%) alive with controlled systemic disease, and 2 (11%) deaths from
      distant metastasis. The Kaplan-Meir survival curve was comparable with other
      studies in the literature. This study found that the frequency of LATC (42%) was
      higher than in most studies. Aggressive surgical therapy to treat these tumors is
      compatible with a low recurrence rate and long-term survival in a significant
      proportion of patients.

PMID- 12056466
TI  - Peripheral cholangiocarcinoma with thoracic spine metastasis: a successful
      surgically treated case.
AB  - In this study we present a rare case of cholangiocarcinoma with metastasis to the
      thoracic spine. A 63-year-old female with peripheral cholangiocarcinoma
      associated with hepatolithiasis presented low back pain as a result of a thoracic
      spine (T12) compression fracture. Spine surgery and pathological examination
      revealed a metastatic mucinous adenocarcinoma of unknown origin. Two weeks after
      the spine surgery, a nontender palpable abdominal mass was found at the
      epigastric area. Abdominal sonography (US), abdominal computed tomography (CT),
      and magnetic resonance cholangiopancreaticogram (MRCP) revealed a hepatic tumor,
      hepatolithiasis, and gallbladder empyema. The patient underwent hepatic
      resection, cholecystectomy, and choledocholithotomy with T-tube stent.
      Pathological examination with immunohistochemical stain revealed hepatolithiasis
      concurrent with mucinous cholangiocarcinoma. Postoperative course was uneventful
      and no recurrence was noted during a 1-year follow-up period.

PMID- 12056467
TI  - Tension-free open mesh repair of ventral hernias--Stoppa's technique.
AB  - Tension-free prosthetic mesh repair of giant, complex, or recurrent ventral
      hernias in the form of a modified Stoppa technique has been used in 60 cases.
      Complication rate has been comparable with other such studies. In obese patients
      with a pendulous anterior abdominal wall, limited panniculectomy was carried out
      while repairing the hernia through a low transverse abdominal incision. None of
      the patients required a progressive preoperative pneumoperitoneum. The incidence
      of wound infection was 5%. One patient had a wound hematoma that required
      evacuation; minor wound complications occurred in 11% cases. The hospital stay
      ranged from 1 to 6 weeks (mean, 10.3 days). One case required readmission for
      resuturing of the wound. None of the cases required removal of the mesh. There
      was no recurrence at follow-up (mean, 26 months) in 80% of the cases. This
      technique is an excellent but somewhat tedious procedure.

PMID- 12056468
TI  - Diverticular disease of the small bowel: report of 27 cases.
AB  - Diverticula of the small bowel are usually asymptomatic but occasionally can
      present with serious complications. Because of the rarity of small bowel
      diverticulosis and the limited case number in most published reports, we analyzed
      one of the largest series with symptomatic small bowel diverticular disease. In
      this retrospective review, we studied 27 symptomatic patients with diverticula of
      the small bowel that was treated surgically. The study included 13 male and 14
      female patients (age range, 30-87 years; mean age, 69.3 years). Fourteen patients
      underwent an elective operation for chronic refractory symptoms. Thirteen
      patients underwent emergency surgery because of rupture of the diverticula and
      associated peritonitis, diverticulitis and small bowel obstruction, or lower
      gastrointestinal bleeding. Surgical treatment consisted of resection of the
      intestinal segment containing the diverticula. All patients were symptom-free
      postoperatively and no "short bowel" problems developed. Abdominal pain,
      gastrointestinal bleeding, and bowel obstruction were the most common clinical
      symptoms. Small bowel diverticulosis should be treated surgically only when
      refractory symptoms or severe complications are present.

PMID- 12056469
TI  - Tissucol application in dermolipectomy and incisional hernia repair.
AB  - Biological adhesives have a lot of applications in surgical procedures. Here we
      present a prospective study with the aim of analyzing results of the application
      of Tissucol between the muscle layers and subcutaneous tissue after incisional
      hernia repair with polypropylene mesh and associated dermolipectomy. We assess
      clinical and technical parameters, local morbidity, and hospital stay. Fifty-six
      patients were divided into two groups. Patients with whom we used fibrin glue
      were older, with more obesity (P < 0.005) with associated diseases, and their
      incisional hernias were larger and more complicated to repair. Patients in the
      Tissucol group developed less local morbidity (hematomas or abscesses; P < 0.01),
      had a shorter mean hospital stay (P < 0.01), and required less wound care. The
      use of Tissucol improves the results of surgical repair of large abdominal
      incisional hernias repaired by mesh placement and dermolipectomy, and it
      decreases global morbidity and hospital stay are reduced.

PMID- 12056471
TI  - Puetz-Jeghers syndrome involving appendix.
AB  - Puetz-Jegher's syndrome is an autosomal dominant hereditary disease, which is
      characterized by hamartomatous polyposis and mucocutaneous pigmentation mainly
      over the circum-oral region. Patients with Peutz-Jeghers syndrome seek medical
      attention whenever there are complications such as intussusception, bleeding from
      the polyps, etc. Occasionally, gastrointestinal tract malignancies have been
      reported in Peutz-Jeghers syndrome. In this paper, we report a patient with Peutz
      Jeghers syndrome who had multiple complications and polyposis involving the
      appendix, because involvement of the appendix is extremely rare in Peutz-Jeghers
      syndrome.

PMID- 12056470
TI  - Immediate breast reconstruction with the transverse rectus abdominis
      musculocutaneous flap after skin-sparing mastectomy.
AB  - Immediate breast reconstruction with the transverse rectus abdominis
      musculocutaneous (TRAM) flap after skin-sparing mastectomy is becoming an
      increasingly performed procedure in patients with ductal carcinoma in situ, early
      invasive breast cancer, and prophylactic mastectomy. Through a periareolar
      approach, it is possible to remove the breast parenchyma along with the nipple
      areola complex, preserving almost all the original skin envelope and the
      inframmamary fold. The TRAM flap is used to recreate the volume and shape of the
      original breast. This technique has higher quality and easier reconstruction. The
      major disadvantages, extensive scar and donor site skin color mismatch, are
      reduced to a minimum level because the former is limited at the natural border of
      the nipple areola and the latter can be effectively concealed with proper nipple
      reconstruction. Thirty-one patients with a mean age of 39 years (range, 26-50
      years) who had undergone unilateral or bilateral mastectomy for early breast
      cancer and immediate breast reconstruction with the pedicled TRAM flap were
      retrospectively reviewed. Requirements for the skin-sparing mastectomy technique
      include suitability of donor site tissue for autologous tissue, early breast
      cancer or ductal carcinoma in situ, and adequate size and shape matching of the
      contralateral breast. There was no observed local recur- rence during the follow
      up period (mean, 20 months; range, 11-30 months). Complications at the recipient
      site include mastectomy skin flap partial necrosis in 2 patients and cellulitis
      of the transferred flap in 1 patient. No total or partial flap necrosis was
      observed. One patient developed abdominal bulging 1 month after the operation,
      during the administration of chemotherapy. All reconstruction was considered very
      satisfactory from an aesthetic perspective by the surgeon and the patient. The
      nicer aesthetic result with oncological safety is achieved with immediate breast
      reconstruction with the TRAM flap after skin-sparing mastectomy. The risk of
      local recurrence is not higher compared with more radical surgical techniques.

PMID- 12056472
TI  - Prescreen evaluation of situs inversus patients.
AB  - Situs inversus is a congenital visceral malrotation anomaly that occurs in
      approximately 2 per 10,000 live births, but it may go unrecognized until
      discovered during emergency surgery. The differential diagnosis in situs inversus
      patients may not be readily seen in the emergency setting. Historical symptoms
      include reversed locations for common physical complaints, whereas physical signs
      can be used to diagnose and treat these patients. Laboratory data may also be
      used to diagnose and treat patients with this anomaly. This study was prompted by
      a postmortem investigation of a patient with situs inversus and dextrocardia.
      Several other cases of congenital malrotation, with attention to anatomical
      variants coupled with medical data, provide guidelines in prescreen evaluation
      and medical/surgical treatment of similar patients. Careful attention to
      laboratory and radiologic findings are paramount to quality patient care and
      prevention of complications. Educating these patients about their malrotation
      would also aid in future treatment.

PMID- 12056473
TI  - Appendiceal mucocoele: a case report and review of the literature.
AB  - Mucocoele of the appendix denotes an obstructive dilatation of the appendiceal
      lumen due to abnormal accumulation of mucus, which may be related to a variety of
      pathological conditions. This may be the outcome of various processes. Most
      important for the surgeon, however, are the mucocoeles that are caused by
      mucinous cystadenomas and cystadenocarcinomas. In the latter case, a possible
      rupture of the mucocoele, either spontaneous or accidental, during surgery may
      result in the clinical condition of pseudomyxoma peritonei, a spread of malignant
      cells throughout the entire peritoneal cavity in the form of multiple mucinous
      deposits. It is therefore important both to identify the disease preoperatively
      and to plan a careful resection to remove the mass. We report one case and
      present the clinical and diagnostic aspects of this disease.

PMID- 12056474
TI  - Experimental inoculation of porcine circoviruses type 1 (PCV1) and type 2 (PCV2)
      in rabbits and mice.
AB  - The objective of this work was to investigate the susceptibility of rabbits and
      mice experimentally inoculated with porcine circoviruses type 1 (PCV1) and type 2
      (PCV2) to infection and development of disease and/or lesions. Forty six New
      Zealand rabbits and 50 ICR-CDI mice were both divided into two groups comprising
      PCVI and PCV2 inoculated animals, and a third group inoculated with non-infected
      cell culture medium. Rabbits were inoculated intranasally while mice were
      inoculated intraperitoneally. Clinical signs and body weights were recorded at
      the start of the experiment and at necropsy. Animals were bled, euthanised and
      necropsied at days 0, 3, 7, 10, 14 and 20 post-inoculation and samples were
      collected for histopathological, serological, in situ hybridisation and PCR
      analysis. No clinical signs or gross and microscopic lesions compatible with PCV2
      infections such as those seen in pigs were observed. No presence of PCV2 nucleic
      acid was detected in rabbits and mice by in situ hybridisation. Only one mouse
      inoculated with PCV1 seroconverted on day 20 P1. PCV1 and PCV2 genome was
      detected in serum by PCR in mice inoculated with each porcine circovirus, while
      rabbits were negative for both viral types. These studies indicated that porcine
      circoviruses did not cause any disease or microscopic lesions in inoculated
      rabbits and mice during the experimental period. However, intraperitoneally
      inoculated mice might have harboured PCV2 in circulation without evidence of
      viral replication.

PMID- 12056475
TI  - Influence of lairage time on some welfare and meat quality parameters in pigs.
AB  - A total of 150 Large White cross Landrace pigs (110-120 kg) of both sexes were
      used to investigate the effects of three different lairage times (0 h, 3 h, 9 h).
      Blood samples were collected at exanguination and cortisol, glucose, lactate,
      muscle enzymes and haematological parameters were determined. Post-mortem
      measurements of muscle pH were taken at 20 min, 2 h and 24 h from Longissimus
      thoracis and Semimembranosus. Lairage time showed a significant effect on pH24,
      internal muscle reflectance using the fibre optic probe (FOP24), red blood cells,
      neutrophils and lymphocytes, glucose and enzymatic activities. Changes in blood
      profile and meat quality parameters indicated that three hours of lairage in
      Spanish commercial conditions may reduce the amount of stress exhibited by pigs
      at slaughter and better meat quality can be obtained. No lairage or an
      excessively long lairage period without food may compromise animal welfare and
      meat quality.

PMID- 12056476
TI  - Prevalence of equine herpesvirus types 2 and 5 in horse populations by using type
      specific PCR assays.
AB  - Equineherpesvirustypes 2 and 5 (EHV-2andEHV-5)have a rather unclearpathogenicity
      and distribution within the equid population. In order to gain more information
      on the prevalence of these two viruses, type-specific PCR assays were developed
      to detect viral DNA in nasal specimens and in peripheral blood leukocytes (PBLs)
      of adult horses and foals from various regions of Europe, i.e. Sweden, Hungary
      and the United Kingdom. In adult horses, the prevalence of EHV-2 in PBLs was up
      to 68% in Sweden and 71% in the United Kingdom. EHV-2 DNA was detected in the
      PBLs from all the foals tested in all countries and most (93%) of the nasal
      specimens also yielded positive results. The prevalence of EHV-5 DNA in the PBLs
      of foals in Hungary was 15 and 24% in adult horses in the United Kingdom. This
      observation was among the very few reports of the presence of EHV-5 in horses. In
      summary, the specific PCR assays revealed important data on the occurrence and
      distribution of EHV-2 and EHV-5 in large horse populations. The findings
      indicated that infection with EHV-5 occurred later than EHV-2 in foals. This
      study may contribute to a better understanding of the etiological role of these
      gammaherpesviruses in equine diseases.

PMID- 12056477
TI  - Early hepatic immune response in rats infected with Fasciola hepatica.
AB  - We investigated the phenotype of the T cells (CD4+ and CD8+) that produced Th1
      (IFN-gamma) and Th2 cytokines (IL-4 and IL-10) during the firsttwo weeks of
      experimental fasciolosis in rats. We also followed the kinetics of the cytokine
      and proliferative responses of hepatic mononuclear cells (HMNC) over the same
      period. We found that HMNC were more numerous in the infected animals than in the
      controls. The percentage of CD4+ cells increased significantly after infection,
      whereas the percentage of CD8+ cells did not change. Moreover, the frequency of
      the cells producing (CP) cytokine changed after infection. The frequency of CP
      IFN-gamma on 7 days postinfection (pi) was similar to that in control animals.
      However, the frequency of CP IFN-gamma was clearly lower on day 14 pi, whereas
      the frequency of CP IL-4 and CP IL-10 had increased. The CP IL-10-were mostly
      CD4+. Mitogenic stimulation (phorbol myristate acetate/ionomycin) of HMNC led to
      an increase in the amounts of the Th2 cytokines in the supernatant on days 7 and
      14 pi, with the increase more pronounced on day 14. In contrast, IFN-gamma levels
      also increased by day 7 pi but then decreased to below control levels by day 14.
      In addition, HMNC proliferation in response to mitogen followed a similar pattern
      to IFN-gamma production. These findings suggested that, during the first 2 weeks
      of infection, F hepatica induced a transient ThO cytokine profile followed by
      downregulation of the cellular response and the induction of a Th2 cytokine
      profile.

PMID- 12056478
TI  - Evaluation of L-selectin expression and assessment of protein tyrosine
      phosphorylation in bovine polymorphonuclear neutrophil leukocytes around
      parturition.
AB  - Impaired polymorphonuclear neutrophil leukocyte (PMN) function around parturition
      has been associated with increased clinical mastitis in dairy cows. Rolling and
      attachment of PMN to the endothelium is the first step in the recruitment process
      and is accomplished by interaction between L-selectin on PMN and its ligand on
      endothelial cells. Furthermore, tyrosine phosphorylation is involved in the
      initiation of many PMN functions. The objective of this work was to determine
      changes in expression of L-selectin and tyrosine phosphorylation in the perinatal
      period. Eight clinically healthy Holstein cows were used as PMN donors at d-21, 
      14, -7,0 (calving), +1, +2, +7, +14, +28. Evaluation of L-selectin expression was
      carried out on activated and resting PMN. Anti-bovine L-selectin monoclonal
      antibody (MAB) and flow cytometric analysis were used to measure the percentage
      of PMN fluorescing and receptor expression (log mean fluorescent channel, LMFC).
      Activated and resting PMN showed similar trends in % PMN fluorescence and LM FC.
      The percentage of PMN fluorescing tended to decrease at parturition, followed by
      a significant increase at d +14 and +28 (P < 0.02). For LMFC a decrease was
      observed on d +1 followed by an increase through d +28 (P < 0.01). Protein
      tyrosine phosphorylation of lysates prepared from PMN isolated throughout the
      study was detected by electrophoresis and western blotting using anti
      phosphotyrosine MAB. Several protein bands were tyrosine phosphorylated. Two of
      these bands (42-44 kDa and 90 kDa) varied in intensity over time. The intensity
      of the 42-44 kDa band gradually increased from d -7, peaked at d +7 (P < 0.03),
      and steadily decreased to d +28 (P < 0.02). Antibody to activated mitogen protein
      kinase reacted with the 42-44 kDa band. Reduced PMN function during the
      periparturient period could be related to reduced L-selectin adhesion molecules
      on the cell surface, and to modulation in the phosphorylation of functionally
      important molecules.

PMID- 12056479
TI  - Blood oxygen binding in hypoxaemic calves.
AB  - Blood oxygen transport and tissue oxygenation were studied in 28 calves from the
      Belgian White and Blue breed (20 healthy and 8 hypoxaemic ones). Hypoxaemic
      calves were selected according to their high respiratory frequency and to their
      low partial oxygen pressure (PaO2) in the arterial blood. Venous and arterial
      blood samples were collected, and 2,3-diphosphoglycerate, adenosine triphosphate,
      chloride, inorganic phosphate and hemoglobin concentrations, and pH, PCO, and PO2
      were determined. An oxygen equilibrium curve (OEC) was measured in standard
      conditions, for each animal. The arterial and venous OEC were calculated, taking
      body temperature, pH and PCO2 values in arterial and venous blood into account.
      The oxygen exchange fraction (OEF%), corresponding to the degree of blood
      desaturation between the arterial and the venous compartments, and the amount of
      oxygen released at the tissue level by 100 mL of blood (OEF Vol%) were calculated
      from the arterial and venous OEC combined with the PO2 and hemoglobin
      concentration. In hypoxaemic calves investigated in this study, the hemoglobin
      oxygen affinity, measured under standard conditions, was not modified. On the
      contrary, in vivo acidosis and hypercapnia induced a decrease in the hemoglobin
      oxygen affinity in arterial blood, which combined to the decrease in PaO2 led to
      a reduced hemoglobin saturation degree in the arterial compartment. However, this
      did not impair the oxygen exchange fraction (OEF%), since the hemoglobin
      saturation degree in venous blood was also diminished.

PMID- 12056480
TI  - Early cytokine response of gnotobiotic piglets to Salmonella enterica serotype
      typhimurium.
AB  - Cytokine response against Salmonella Typhimurium is traditionally studied in
      conventional animals. Germ-free animals, however, enable to study response
      against infection without background effect of other microorganisms. Plasma and
      ileal inflammatory cytokines in germ-free piglets orally infected with virulent
      LT2 strain or, with a non-virulent SF1591 rough mutant were quantified by ELISA.
      In plasma and ileal washes, IFN-gamma levels significantly increased in both
      infected groups. TNF-alpha and IL-18 were mostly missing in plasma 24 h after
      infection. In the ileum, IFN-gamma, TNF-alpha, and IL-1beta were induced mainly
      by the virulent strain, whereas IL-18 was induced in highest quantity by non
      virulent Salmonella. These data confirmed an important role of IFN-gamma, as well
      as other inflammatory cytokines in early stage of salmonellosis.

PMID- 12056481
TI  - Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall
      like protein.
AB  - Under physiological conditions canines transport vitamin A in blood plasma
      primarily as retinyl esters bound to lipoproteins and excrete substantial amounts
      of vitamin A as retinol and retinyl esters with urine. In the aqueous environment
      of urine, the hydrophobic vitamin A has to be associated with a protein. This
      vitamin A-protein complex was purified to homogeneity, prepared by preparative
      ultracentrifugation (density 1.21 g/mL), native polyacrylamide gel
      electrophoresis (PAGE) and size exclusion chromatography. The vitamin A-protein
      complex has a high molecular mass of > 5,000 kDa under native conditions. SDS
      PAGE under reduced conditions revealed a single band with a molecular mass of
      about 100 kDa for the protein moiety. Peptides obtained after limited proteolysis
      with trypsin from the 100 kDa protein were characterised by MALDI-TOF mass
      spectrometry and showed amino acid sequence homology to the human Tamm-Horsfall
      Protein (THP). This was further confirmed by a positive immunoreaction of the
      isolated protein with crossreacting human THP antibodies. The localisation of THP
      in dog kidneys was determined by using immunohistology. The reaction was strong
      along the entire thick ascending limb ofthe Henle loop and distal convoluted
      tubule. Our data point to the possibility that THP functions as a novel carrier
      for vitamin A in the urine of canines.

PMID- 12056483
TI  - Evaluation of the hepatic NK cell response during the early phase of Fasciola
      hepatica infection in rats.
AB  - The in situ distribution of NK cells in rat liver during the first 28 days of an
      experimental infection with F hepatica was investigated. NK cells were
      distributed homogeneously throughout the hepatic parenchyma in uninfected
      animals. The total number of hepatic mononuclear cells increased significantly
      following infection, but the proportion of NK cells did not change. After
      infection, these cells were found around the portal space, around the
      centrolobular vein, in the periportal fibrosis and in the band of collagen.
      However, no NK cells could be detected in or around the granuloma during
      infection. The frequency of both I L-2- and IFNgamma-producing NK cells was
      higher on day 7 postinfection (pi) but only the percentage of IFNgamma -CD161+
      subsets remained elevated thereafter, whereas the percentage of both IL-2+CD161+
      and IL-4+CD161+ subsets returned to the baseline. The number of CD161+IL10+ cells
      did not change significantly. These results suggest that NK cells could be
      another source for the early production of IFNgamma but provide no evidence that
      these cells are involved in early events associated with granuloma formation.

PMID- 12056482
TI  - Protection evaluation against Chlamydophila abortus challenge by DNA vaccination
      with a dnaK-encoding plasmid in pregnant and non-pregnant mice.
AB  - Mice were intramuscularly immunized with a dnaK-encoding DNA plasmid. The
      protective effect of DNA immunization against Chlamydophila abortus infection was
      studied in pregnant and non-pregnant mice models. In non-pregnant mice, the dnaK
      vaccine induced a specific humoral response with the predominant IgG2a isotype,
      which failed to have in vitro neutralizing properties. No delayed-type
      hypersensitivity reaction was observed and the spleens of dnaK vaccinated-mice
      were not protected against C. abortus challenge. In pregnant mice, the dnaK
      vaccine induced a non-specific partial protection from abortion. This may be due
      to the immunogenic properties of the CpG motifs of bacterial DNA present in the
      vaccinal plasmid backbone. Nevertheless, spleens of dnaK vaccinated-pregnant mice
      were not protected.

PMID- 12056484
TI  - Production and characterization of a thermostable glucoamylase from
      Streptosporangium sp. endophyte of maize leaves.
AB  - Thermostable amylolytic enzymes are currently investigated to improve industrial
      processes of starch degradation. Streptosporangium sp. an endophytic actinomycete
      isolated from leaves of maize (Zea mays L.) showed glucoamylase production, using
      starch-Czapek medium, and the highest rate was obtained in the initial growth
      phase, after incubation for 24 h at pH 8.0. Maximum glucoamylase activity (158 U
      mg(-1) protein) was obtained at pH 4.5 and 70 degrees C. The isolated enzyme
      exhibited thermostable properties as indicated by retention of 100% of residual
      activity at 70 degrees C for 30 min with total inhibition at 100 degrees C.
      Extracellular enzyme from Streptosporangium sp. was purified by fractionated
      precipitation with ammonium sulphate. After 60% saturation produced 421 U mg(-1)
      protein, and yield was 74% with purification 2.7 fold. The enzyme produced by
      Streptosporangium sp. has potential for industrial applications.

PMID- 12056485
TI  - Optimisation of biodiesel production by sunflower oil transesterification.
AB  - In this work the transformation process of sunflower oil in order to obtain
      biodiesel by means of transesterification was studied. Taguchi's methodology was
      chosen for the optimisation of the most important variables (temperature
      conditions, reactants proportion and methods of purification), with the purpose
      of obtaining a high quality biodiesel that fulfils the European pre-legislation
      with the maximum process yield. Finally, sunflower methyl esters were
      characterised to test their properties as fuels in diesel engines, such as
      viscosity, flash point, cold filter plugging point and acid value. Results showed
      that biodiesel obtained under the optimum conditions is an excellent substitute
      for fossil fuels.

PMID- 12056486
TI  - The yield and composition of switchgrass and coastal panic grass grown as a
      biofuel in southern England.
AB  - Switchgrass (Panicum virgatum L.) and coastal panic grass (Panicum amarum A.S.
      Hitchc. & Chase) are perennial grasses indigenous to North America. Switchgrass
      has been shown to have good potential as a biofuel crop in both the US and
      Canada. In the study reported here, seven varieties of switchgrass and one panic
      grass were evaluated for 5 years under the temperate maritime conditions in
      Southern England. Both species had 0 or 60 kg N ha(-1) applied annually in spring
      as treatment. Yield was measured after flowering and when stems were dead in the
      winter. Yield increased annually for 4-5 years except for the variety Dacotah,
      and in the fifth year dead stem yields ranged from 8.82 to 13.97 t dm ha(-1).
      There was no response to N except for one variety in one year. Mineral
      concentration in biomass was higher at flowering than at dead stem harvest and
      delaying harvesting further provided more time for P, K and Cl to be leached but
      yield also declined.

PMID- 12056487
TI  - Immobilized Candida antarctica lipase-catalyzed alcoholysis of cotton seed oil in
      a solvent-free medium.
AB  - The alcoholysis (transesterification) of the refined cotton seed oil of Turkish
      origin with primary and secondary alcohols was investigated in the presence of an
      immobilized enzyme from Candida antarctica, commercially called Novozym 435 in a
      solvent-free medium. The optimum conditions of the methanolysis were as follows:
      30% enzyme based on oil weight; oil/alcohol molar ratio 1:4; temperature: 50
      degrees C and reaction time: 7 h. Maximum methyl esters (ME) yield was 91.5%. At
      the same conditions cotton seed oil was converted with short-chain primary and
      secondary alcohols to its corresponding esters with conversions between 72% and
      94%. Our results indicated that alcoholysis products of cotton seed oil could be
      used as valuable intermediates in oleochemistry.

PMID- 12056488
TI  - Operational factors and nutrient effects on activated sludge treatment of Pinus
      radiata kraft mill wastewater.
AB  - The biodegradability of Pinus radiata bleached kraft mill wastewater by an
      activated sludge treatment during a period of 280 days was evaluated. The effect
      of varying hydraulic retention time (HRT) in the range of 48 to 4.5 h and
      nitrogen (N) and phosphorus (P) addition on removal of biological oxygen demand
      (BOD5), chemical oxygen demand (COD), suspended solids (TSS and VSS), total
      phenolic compounds, tannin and lignin and reduction of toxicity was investigated.
      Removal of BOD5 was higher than 90% when HRT varied from 16 to 6 h, but decreased
      when HRT was less than 6 h. Similar performance was observed for COD removal,
      which was about 60% when HRT was varied from 16 to 6 h. Removal of total phenolic
      compounds and tannin and lignin was seriously affected by HRT. N and P addition
      to maintaining a ratio of 100:5:0.3 provided optimal BOD5, COD and suspended
      solids removal when HRT varied from 16 to 7 h, and no toxicity (using Daphnia)
      was detected in the treated effluent. When HRT was less than 6 h, the system
      showed destabilisation and pH, COD, BOD5 and suspended solids removal decreased.

PMID- 12056489
TI  - Ethanol-acetone pulping of wheat straw. Influence of the cooking and the beating
      of the pulps on the properties of the resulting paper sheets.
AB  - The influence of independent variables in the pulping of wheat straw by use of an
      ethanol-acetone-water mixture [processing temperature and time, ethanol/(ethanol
      + acetone) value and (ethanol + acetone)/(ethanol + acetone + water) value] and
      of the number of PFI beating revolutions to which the pulp was subjected, on the
      properties of the resulting pulp (yield and Shopper-Riegler index) and of the
      paper sheets obtained from it (breaking length, stretch, burst index and tear
      index) was examined. By using a central composite factor design and the BMDP
      software suite, equations that relate each dependent variable to the different
      independent variables were obtained that reproduced the experimental results for
      the dependent variables with errors less than 30% at temperatures, times,
      ethanol/(ethanol + acetone) value, (ethanol + acetone)/(ethanol + acetone +
      water) value and numbers of PFI beating revolutions in the ranges 140-180 degrees
      C, 60-120 min, 25-75%, 35-75% and 0-1750, respectively. Using values of the
      independent variables over the variation ranges considered provided the following
      optimum values of the dependent variables: 78.17% (yield), 15.21 degrees SR
      (Shopper-Riegler index), 5265 m (breaking length), 1.94% (stretch), 2.53 kN/g
      (burst index) and 4.26 mN m2/g (tear index). Obtaining reasonably good paper
      sheets (with properties that differed by less than 15% from their optimum values
      except for the burst index, which was 28% lower) entailed using a temperature of
      180 degrees C, an ethanol/(ethanol + acetone) value of 50%, an (ethanol +
      acetone)/(ethanol + acetone + water) value of 75%, a processing time of 60 min
      and a number of PFI beating revolutions of 1750. The yield was 32% lower under
      these conditions, however. A comparison of the results provided by ethanol,
      acetone and ethanol-acetone pulping revealed that the second and third process
      which provided an increased yield were the best choices. On the other hand, if
      the pulp is to be refined, ethanol pulping is the process of choice.

PMID- 12056490
TI  - Wastewater sludge as a substrate for growth and carrier for rhizobia: the effect
      of storage conditions on survival of Sinorhizobium meliloti.
AB  - The inoculation of legumes with rhizobia is used to maximise nitrogen fixation
      and enhance the plant yield without using N fertilisers. For this reason many
      inoculant types were developed and optimised. In our study, the effects of the
      growth medium, the carrier, the temperature and the storage period were
      determined on the survival of Sinorhizobium meloliti. Secondary sludge from
      Communaute Urbaine de Quebec wastewater treatment plant and standard medium (YMB)
      were used for rhizobial growth. Dehydrated sludge from Jonquiere wastewater
      treatment plant, peat and a mixture of peat and sludge were used as carrier
      materials. Results showed that the wastewater sludge offered better protection
      for rhizobia survival during freezing and thawing at -20 degrees C than the
      standard medium. In general, results also showed the suitability of using sludge
      as a carrier because it had the same or a higher potential than peat to support
      survival of S. meliloti. In the case of YMB-grown rhizobia, peat- and sludge
      based carriers appeared to be similar in terms of survival rate during the
      storage at 4 and 25 degrees C. For secondary sludge-grown rhizobia, the survival
      was better in sludge than in peat based carrier. Generally, the cell count
      remained higher than 10(8) cells/g for up to 80 days at 4 and 25 degrees C in
      both carriers (sludge and peat). However, for the secondary sludge-grown cells
      stored in peat-based carrier at 4 degrees C, the viable cells decreased under
      10(8) cells/g at the 81st day of storage but remained acceptable compared to the
      standard (10(7) cells/g of carrier).

PMID- 12056491
TI  - Sugarcane bagasse as alternative packing material for biofiltration of benzene
      polluted gaseous streams: a preliminary study.
AB  - Removal of benzene vapor from gaseous streams was studied in two identically
      sized lab-scale biofiltration columns: one filled with a mixture of raw sugarcane
      bagasse and glass beads, and the other one packed with a mixture of ground
      sugarcane bagasse and glass beads, in the same volume ratio, as filter materials.
      Separate series of continuous tests were performed, in parallel, under the same
      operating conditions (inlet benzene concentration of 10.0, 20.0 or 50.0 mg m(-3),
      and superficial gas velocity of 30.6, 61.2 or 122.4 m h(-1)) in order to evaluate
      and compare the influence of the packing material characteristics upon the
      biofilter effectiveness. The maximum elimination capacities obtained, at an inlet
      load of 6.12 g m(-3) h(-1), were 3.50 and 3.80 g m(-3)packibng material h(-1)
      with raw and ground sugarcane bagasse, respectively. This was a preliminary study
      and the results obtained suggest only a limited application with more work
      needed.

PMID- 12056492
TI  - Calcium interference with continuous biosorption of zinc by Sargassum sp.
      (Phaeophyceae) in tubular laboratory reactors.
AB  - The zinc biosorptive capacity of the brown seaweed Sargassum sp. (Phaeophyceae)
      was studied in the presence or absence of competing calcium ions, using a
      continuous system with tubular fixed-bed reactors. In order to detect the effect
      of calcium on zinc biosorption, a 130 mg/l zinc solution was used, and calcium
      was added at 50-340 mg/l. The potential zinc biosorptive capacity of the biomass
      was markedly influenced by the presence of ionic calcium. Zinc sorption decreased
      with increasing calcium concentrations, as expressed by zinc uptake rates.
      Calcium was effectively recovered only during the initial stages of the process,
      as expressed by the decrease in its uptake rates. Calcium uptake rates were also
      much higher than zinc uptake rates, indicating that calcium was preferentially
      recovered when compared to zinc.

PMID- 12056493
TI  - Diffusion of sulfuric acid within lignocellulosic biomass particles and its
      impact on dilute-acid pretreatment.
AB  - Intra-particle diffusion of sulfuric acid into sugarcane bagasse, corn stover,
      rice straw and yellow poplar was investigated to determine the effective
      diffusivity of sulfuric acid within the porous biomass structure. Diffusion
      experiments were conducted over 25-75 degrees C for two different biomass sizes
      using dynamic diffusion test cells. Diffusivities of sulfuric acid in
      agricultural residues were significantly higher than those of hard wood.
      Diffusivity data for each biomass were fitted into the Arrhenius equation for
      extrapolation to higher temperatures. The diffusivity data were subsequently
      incorporated into a theoretical model to determine acid profile within the
      biomass matrix. The modeling results indicate that intra-particle diffusion of
      acid influences the rate of dilute-acid pretreatment if unground biomass
      feedstock is used under normal pretreatment conditions. A criterion was set up to
      determine the critical biomass size at which the intra-particle acid diffusion
      becomes a rate-influencing factor for a given pretreatment condition.

PMID- 12056494
TI  - Performance comparison of experimental constructed wetlands with different filter
      media and macrophytes treating industrial wastewater contaminated with lead and
      copper.
AB  - The aim of this study was to investigate the treatment efficiency of passive
      vertical-flow wetland filters containing different macrophytes (Phragmites and/or
      Typha) and granular media with different adsorption capacities. Gravel, sand,
      granular activated carbon, charcoal and Filtralite (light expanded clay) were
      used as filter media. Different concentrations of lead and copper sulfate were
      added to polluted urban stream inflow water to simulate pretreated mine
      wastewater. The relationships between growth media, microbial and plant
      communities as well as the reduction of predominantly lead, copper and five-day
      biochemical oxygen demand (BOD5) were investigated. An analysis of variance
      showed that concentration reductions (mg l(-1)) of lead, copper and BOD5 were
      significantly similar for the six experimental wetlands. Microbial diversity was
      low due to metal pollution and similar for all filters. There appears to be no
      additional benefit in using adsorption media and macrophytes to enhance biomass
      performance during the first 10 months of operation.

PMID- 12056495
TI  - Growth of ornamental plants in two composts prepared from agroindustrial wastes.
AB  - Two composts prepared from agroindustrial wastes were assayed as substrates: C1
      from brewing waste (yeast and malt) plus lemon tree prunings; and C2 from the
      solid fraction of olive mill wastewater plus olive leaves. Sixteen substrates
      were prepared by combining each compost with Sphagnum peat or a commercial
      substrate (CS) in different proportions. The nutrients (N and K) provided by the
      composts, which acted as slow-release fertilisers, influenced especially the
      development of calendula, although the physical and physico-chemical properties
      such as total pore space and electrical conductivity (EC) were also relevant. On
      the other hand, in the salt-sensitive calceolaria hybrid, EC and chloride
      concentration were the main factors influencing growth. Adequate substrates for
      the development of calendula can be prepared by mixing C1 at up to 75% with peat
      or at up to 50% with CS, and C2 at up to 50% with peat or CS. For calceolaria,
      the substrate should have a lower proportion of compost, C1 at up to 50% and C2
      at up to 25%, both mixed with peat or CS. Therefore, composts of agroindustrial
      origin such as these can be used as an alternative to peat and CSs for growing
      ornamental plants. provided the mixture contains at least 25% peat or CS.

PMID- 12056496
TI  - SCP and crude pectinase production by slurry-state fermentation of lemon pulps.
AB  - Single cell protein (SCP) and crude pectinolytic enzymes production from citrus
      pulps is reported. SCP and enzymes were produced by slurry-state flask
      cultivation of Aspergillus niger and Trichoderma viride on pulps from lemon juice
      clarification. Production as well as crude pectinase activity was not affected by
      the high dry matter content of the pulps. Both the protein content in the residue
      and the enzyme activity in the supernatant were higher in T. viride than in A.
      niger culture. The crude pectinase of T. viride, whose specific activity was
      similar to that found for a commercial concentrated preparation, could be
      utilized in the same citrus processing factory as well as in other factories
      which use large amounts of pectinolytic crude preparations, for example to
      enhance depuration plant performance.

PMID- 12056497
TI  - Arundo donax cane as a precursor for activated carbons preparation by phosphoric
      acid activation.
AB  - Canes from Arundo donax, a herbaceous rapid-growing plant, were used as precursor
      for activated carbon preparation by phosphoric acid activation under a self
      generated atmosphere. The influence of the carbonization temperature in the range
      400-550 degrees C and of the weight ratio phosphoric acid to precursor (R = 1.5
      2.5) on the developed porous structure of the resulting carbons was studied for 1
      h of carbonization time. Surface properties of the activated carbons were
      dependent on a combined effect of the conditions employed. Carbons developed
      either with R = 1.5 over the range 400-500 degrees C, or with R = 2 at 500
      degrees C exhibited surface areas of around 1100 m2/g, the latter conditions
      promoting a larger pore volume and enhanced mesoporous character. For both
      ratios, temperature above 500 degrees C led to reduction in porosity development.
      A similar effect was found for the highest ratio (R = 2.5) and 500 degrees C. The
      influence of carrying out the carbonization either for times shorter than 1 h or
      under flowing N2 was also examined at selected conditions (R = 2, 500 degrees C).
      Shorter times induced increase in the surface area (approximately 1300 m2/g),
      yielding carbons with smaller mean pore radius. Activated carbons obtained under
      flowing N2 possessed predominant microporous structures and larger ash contents
      than the samples derived in the self-generated atmosphere.

PMID- 12056498
TI  - State-specific mortality from stroke and distribution of place of death--United
      States, 1999.
AB  - In the United States, stroke is the third leading cause of death and one of the
      major causes of serious, long-term disability among adults. Each year,
      approximately 500,000 persons suffer a first-time stroke, and approximately
      167,000 deaths are stroke-related. This report presents national and state
      specific death rates for stroke in 1999, which indicate state-by-state variations
      in both stroke-related death rates and the proportions of stroke decedents who
      die before transport to an emergency department (ED). Prevention through public
      and medical education remains a key strategy for reducing stroke-related deaths
      and disability.

PMID- 12056499
TI  - Fetal alcohol syndrome--Alaska, Arizona, Colorado, and New York, 1995-1997.
AB  - Fetal alcohol syndrome (FAS) is caused by maternal alcohol use during pregnancy
      and is one of the leading causes of preventable birth defects and developmental
      disabilities in the United States. FAS is diagnosed on the basis of a combination
      of growth deficiency (pre- or postnatal), central nervous system (CNS)
      dysfunction, facial dysmorphology, and maternal alcohol use during pregnancy.
      Estimates of the prevalence of FAS vary from 0.2 to 1.0 per 1,000 live-born
      infants. This variation is due, in part, to the small size of the populations
      studied, varying case definitions, and different surveillance methods. In
      addition, differences have been noted among racial/ethnic populations. To monitor
      the occurrence of FAS, CDC collaborated with five states (Alaska, Arizona,
      Colorado, New York, and Wisconsin*) to develop the Fetal Alcohol Syndrome
      Surveillance Network (FASSNet). This report summarizes the results of an analysis
      of FASSNet data on children born during 1995-1997, which indicate that FAS rates
      in Alaska, Arizona, Colorado, and New York ranged from 0.3 to 1.5 per 1,000 live
      born infants and were highest for black and American Indian/Alaska Native
      populations. This study demonstrates that FASSNet is a useful tool that enables
      health care professionals to monitor the occurrence of FAS and to evaluate the
      impact of prevention, education, and intervention efforts.

PMID- 12056500
TI  - Nonfatal self-inflicted injuries treated in hospital emergency departments-
      United States, 2000.
AB  - CDC, in collaboration with the Consumer Product Safety Commission (CPSC),
      expanded CPSC's National Electronic Injury Surveillance System (NEISS) in July
      2000 to include all types and external causes of nonfatal injuries treated in
      U.S. hospital emergency departments (EDs). This ongoing surveillance system,
      called NEISS All Injury Program (NEISS-AIP), provides data to calculate national
      estimates for nonfatal injuries treated in EDs during 2000. This report provides
      national, annualized, weighted estimates of nonfatal self-inflicted injuries
      treated in U.S. hospital EDs. Overall, self-inflicted injury rates were highest
      among adolescents and young adults, particularly females. Most (90%) self
      inflicted injuries were the result of poisoning or being cut/pierced with a sharp
      instrument, and 60% were probable suicide attempts. NEISS-AIP data increase
      understanding of self-inflicted injuries and can serve as a basis for monitoring
      trends, facilitating additional research, and evaluating intervention approaches.

PMID- 12056501
TI  - Clinically integrated studies in pathology: their contribution to atherosclerosis
      research.
AB  - This article, prepared in honor of Daria Haust, reviews some features of research
      into atherosclerosis and coronary heart disease over the past 150 years, and
      beyond. Attention is drawn to problems arising when people of strong personality
      dominate a particular field of research to the exclusion of pertinent
      observations that do not fit neatly into their particular paradigm. As the world
      becomes more complex and, in theory at least, communications between scientists
      become easier, these dangers are not necessarily diminished. Clinical medicine in
      its broadest sense must continue to relate in the traditional way to the
      specialties grouped within pathology. Undergraduates must receive instruction
      concerning the importance of the historical record and an understanding of the
      nature of science, its strengths, limitations, and boundaries.

PMID- 12056502
TI  - Relevance of hypercholesterolemia to fetal and pediatric atherosclerosis.
AB  - Ubiquitous atherosclerotic changes in fetal and pediatric subjects demonstrate
      the fundamental importance of repetitive hemodynamic stresses and cannot be
      explained on the basis of the hypercholesterolemic/lipid hypothesis because serum
      cholesterol levels at this age lie within allegedly "desirable blood levels."
      This fact, inconsistent with the lipid hypothesis, renders absurd the widespread
      dietary restriction of cholesterol and animal fats as prevention of
      atherosclerosis. Iatrogenic effects of atherosclerosis in humans and its
      experimental production in herbivores at serum cholesterol levels below infant
      levels strongly support the "vascular fatige" concept and negate the lipid
      hypothesis. Neither is atherosclerosis a manifestation of senescence because age
      is merely a time factor indicating the duration of exposure to hemodynamic
      stresses that are variable with time and location.

PMID- 12056503
TI  - Bradykinin as a major endogenous regulator of endothelial function.
AB  - Healthy vascular endothelium is a powerful generator of nitric oxide (NO),
      prostacyclin (PGI2), prostaglandin E2 (PGE2), and plasminogen activator (t-PA).
      These endothelial products protect vascular wall against aggression from
      activated blood platelets and leukocytes. In particular they protect against
      thrombosis, promote thrombolysis, maintain tissue perfusion, and inhibit
      remodeling of vascular and cardiac walls. Endothelial dysfunction appears on one
      hand as suppression in the release of the above mediators, and on the other as
      deleterious discharge of prostaglandin endoperoxides (PGH2, PGG2), superoxide
      anion O2-, peroxynitrite (ONOO-), and plasminogen activator inhibitor (PAI-1).
      Our data point to endothelial bradykinin (Bk) as a trigger for protective
      endothelial mechanisms. In cultured endothelial cells (CEC) Bk through kinin B2
      receptors raised in a concentration-dependent manner (1pM-10 nM) free cytoplasmic
      calcium ions [Ca2+]i. This rise was accompanied by the release of NO as
      quantified by a porphyrinic sensor. Other endothelial agonists were weaker
      stimulators of [Ca2+]i than Bk. In vivo we analyed the effects of exogenous Bk
      and of amplifiers of endogenous Bk, such as perindopril and quinapril ("tissue
      type" angiotensin converting enzyme inhibitors, ACE-I) on endothelial function
      using our original thrombolytic bioassay and EIA assays for 6-keto-PGF1alpha and
      t-PA antigen. A major difference found between exogenuous Bk and endogenous Bk
      (that rendered by "tissue ACE-I") was a) prolonged thrombolytic action (> 4h) of
      quinapril or perindopril. Moreover, only exogenous Bk evoked an immediate and
      profound hypotensive action. In vivo, Bk-induced thrombolysis was B2 kinin
      receptor-dependent, PGI2-mediated. The unexpected action of Bk came to light in
      CEC. Then appeared incubated for 4 h increased expression of mRNAs for
      haemoxygenase (HO-1), cyclooxygenase 2 (COX-2), prostaglandin E synthase (PGE-S),
      but hardly for nitric oxide synthase 2(NOS-2). We hypothesize that a network of
      interactions of Bk-induced enzymes may constitute a delayed phase of Bk effects
      in the endothelium, whereas the primary phase would be activation by BK of
      [Ca2+]i-dependent constitutive endothelial enzymes. In blood-perfused rat
      endotoxemic lungs, NO is the most eminent cytoprotective mediator. Summing up, in
      peripheral circulation endogenous Bk is the most efficient activator of
      protective endothelial function. Thrombolytic action of "tissue-type" ACE-Is
      relies on receptor B-2-mediated, [Ca2+]i-dependent release of PGI2. Bk also may
      act as a "microcytokine" by inducing mRNAs for HO-1, COX-2, or PGE-S. Activation
      of HO-1 may lead to a deficiency in intracellular heme required as a cofactor for
      both COX and NOS. This network of interactions triggered by Bk call for further
      studies.

PMID- 12056505
TI  - Evolution of cholesterol concept of atherogenesis from Anitchkov to our days.
AB  - Our review addresses the development of the cholesterol concept of atherogenesis
      from the classical investigations of Anitchkov and Chalatov (1913), who induced
      experimental cholesterol atherosclerosis in rabbits, to the present time. We
      conclude that based on data obtained to date relating to the presence of
      different classes of lipoproteins in blood, on the role of peroxidatively
      modified low density lipoproteins in atherogenesis, and on the involvement of
      various arterial and blood cells and other factors, the cholesterol concept of
      atherogenesis has not lost its significance. Moreover, cholesterol-lowering
      therapy has a leading role in the primary and secondary prevention of coronary
      heart disease events and other clinical manifestations of atherosclerosis.

PMID- 12056504
TI  - Acute phase serum amyloid A, cholesterol metabolism, and cardiovascular disease.
AB  - Our review examines the nature of serum amyloid A, its isoforms and, their
      structure, the manner of induction of the acute phase forms and argument for and
      against their possible physiological function (s). In this context, the possible
      role of serum amyloid A as a prognostic indicator of unstable angina and its
      significance in relation to cardiovascular disease is discussed.

PMID- 12056506
TI  - The development of structure and function in the postnatal human cerebral cortex
      from birth to 72 months: changes in thickness of layers II and III co-relate to
      the onset of new age-specific behaviors.
AB  - HYPOTHESIS: The thickness of a cortical layer is a composite measure of neuronal,
      axonal, dendritic, synaptic, and glial numbers and sizes that may relate to
      thefunction of a cortical area. METHODS: 35 age-specific behaviors with defined
      cortical localization whose onset lies between birth and 72 months were selected.
      Each behavior's function localized to one or more of 12 cytoarchitectonic areas
      (Brodmann areas 4, with homuncular subdivisions for leg, trunk, face, and hand,
      plus 17, 18, 19, 20, 21, 24, 36, and 37). Data on cortical thickness for each
      layer of 41 cytoarchitectonic areas (including the 12 above) of the postnatal
      human cerebral cortex from birth of 72 months were analyzed for general patterns
      of change. For the 12 cortical areas functionally related to theage-specific
      behaviors, we searched for layer thickness changes that co-related to when the
      behaviors began. RESULTS: Without exception, all layers of the 41 cortical areas
      of the postnatal human cerebral cortex studied develop through a series of
      repeated thinning and thickening in a wave-like fashion. With regard to the co
      relation of behavioral onset and changes in cortical layer thickness, from birth
      to 15 months, only layer II has agreater than expected frequency of being the
      layer with the greatest relative change in thickness (relative to its previous
      value). From 15 to 72 months, only layer IlI has a greater than expected
      frequency of being the layer with the greatest absolute change in thickness (81%
      involved a change in its direction of growth (thinning <--> thickening)). The co
      occurrence of directional growth change and having the greatest layer thickness
      change were only statistically significant for layer III when an age-specific
      behavior began and was not seen for the 41 cortical areas overall (p = 0.014).
      CONCLUSIONS: Cortical laminar development exhibits aprocess that is
      mathematically consistent with a random walk with drift and with boundaries so
      that uncontrolled proliferation and pruning are prevented. The directional
      changes in layer growth could be controlled by feedback coupled with growth
      promoting and growth inhibiting factors. Layer II, with its function of
      establishing local corticocortical connections, appears to be most important in
      establishing age-specific behaviors of infants from birth to 15 months. Such a
      process tends to produce relatively simpler behaviors. LayerIII, with its
      function of establishing longer distance corticocortical connections, appears to
      be most important in establishing age-specific behaviors of children from 15 to
      72 months. This process tends to produce richer, more cross-modal behaviors than
      those mediated primarily by local corticocortical interactions.

PMID- 12056507
TI  - Multifocal myocardial necrosis: a distinctive cardiac lesion in cystic fibrosis,
      lipomatous pancreatic atrophy, and Keshan disease.
AB  - Multifocal myocardial necrosis (MMN) is an unusual cardiomyopathy of childhood,
      characterized by multiple patchy areas of myocardial fiber necrosis/fibrosis
      involving mainly the middle part of the left ventricle, but also, to a lesser
      extent, the right ventricle and the atria. These necrotic lesions are isolated
      and are not accompanied by an inflammatory reaction or vascular alterations. They
      are responsible for acute cardiac failure. MMN lesions are observed in various
      pathologic conditions including cystic fibrosis of the pancreas, pancreatic
      lipomatous hypoplasia/atrophy, malnutrition due to extensive intestinal resection
      with subsequent total parenteral feeding, and in Keshan disease. MMN is the main
      and the most characteristic feature of Keshan disease, an endemic and idiopathic
      condition affecting Chinese rural children. The causes and mechanisms of MMN
      presently are unknown. However, the presence of similar cardiac lesions in such
      different pathological conditions suggests the role of a selective deficiency of
      a hypothetical extrinsic factor (selenium, molybdenum iodide, other), probably
      crucial for the metabolism of the myocardial fiber.

PMID- 12056508
TI  - Adrenergic mechanisms in antinociceptive effects of non steroidal anti
      inflammatory drugs in acute thermal nociception in mice.
AB  - OBJECTIVE: The interactions of alpha-adrenoceptors with the antinociceptive
      effects of non-steroidal antiinflammatory drugs (NSAIDs) were assessed in acute
      thermal nociception in mice. MATERIALS AND METHODS: The analgesic effect was
      analyzed by the tail-flick test. RESULTS: The pretreatment with yohimbine (1
      mg/kg i.p.), 30 min prior to the intraperitoneal injection of ketoprofen (50
      mg/kg), diclofenac (30 mg/kg) and piroxicam (50 mg/kg) antagonized the
      antinociception induced by these NSAIDs, significantly reducing the tail-flick
      latency. Yohimbine did not affect paracetamol (125 mg/kg) induced
      antinociception. Prazosin (1 mg/kg i.p.) antagonized only the effect of
      paracetamol, without affecting the latency of the other drugs. When NSAIDs were
      administered i.t. (ketoprofen 2 m/kg; diclofenac 0.9 mg/kg; piroxicam 1.5 mg/kg;
      paracetamol 3.75 mg/kg), the same results were obtained after i.p. pretreatment
      with yohimbine and prazosin. The pretreatment of phenoxybenzamine (1 mg/kg i.p.)
      antagonized all antinociceptive effects. CONCLUSIONS: NSAIDs induced
      antinociception in an acute thermal pain model without inflammation. The
      mechanism of antinociception induced by ketoprofen, diclofenac and piroxicam
      involves an activation of alpha2-adrenoceptors at spinal and supraspinal levels,
      while paracetamol-induced antinociception is probably due mainly to central
      activation of the descending noradrenergic inhibitory system by alpha1
      adrenoceptors.

PMID- 12056509
TI  - Protective effect of ketoprofen lysine salt on interleukin-1beta and bradykinin
      induced inflammatory changes in hamster cheek pouch microcirculation.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of topically
      applied ketoprofen lysine salt (KLS), a cyclooxygenase inhibitor, against the
      inflammatory changes induced by interleukin-1beta (IL-1beta) and bradykinin (BK)
      in hamster cheek pouch microcirculation. In addition, we characterised the
      pharmacological regulation of IL-1beta activity in this model. MATERIALS AND
      METHODS: Male Syrian hamsters were used. Microcirculation was visualised by
      fluorescent microscopy. Leukocyte adhesion, permeability, perfused capillary
      length (PCL) and capillary red blood cell (RBC) velocity were evaluated.
      TREATMENTS: KLS (25 microg/ml/min to 1.6 mg/ml/min) was topically applied for 3
      min before topically administered IL-1beta (1microg/ml) and BK (10(-4) M).
      Monoclonal anti-mouse IL-1beta receptor antagonist (200 ng/ml), BK-B2 receptor
      antagonist (10(-6) M), PAF inhibitor (10(-5) M) and cycloheximide (10 microg/ml)
      were added topically 15, 10, 15 and 60 min, respectively, before IL-1beta (1
      microg/ml). RESULTS: IL-1beta caused a significant increase in microvascular
      permeability, a decrease in capillary RBC velocity followed by increased
      leukocyte adhesion in postcapillary venules. BK caused a marked increase in
      leukocyte adhesion and no decrease in PCL and RBC velocity. Treatment with KLS
      significantly inhibited both the leukocyte adhesion and microvascular leakage
      induced by the two mediators. The inflammatory effects induced by IL-1beta were
      reduced by blockade of IL-1beta receptors and by a BK-B2 receptor antagonist but
      were not affected by a PAF antagonist and protein synthesis inhibition.
      CONCLUSIONS: These results demonstrate that KLS is effective in preventing early
      inflammatory changes induced by both IL-1beta and BK in the capillary network.
      Prostaglandin release and BK are essential components for IL-beta mediated
      responses, whereas neither PAF nor new protein synthesis appear to be linked to
      the early inflammatory changes induced by IL-1beta.

PMID- 12056510
TI  - TNF tolerance and cytotoxicity in the liver: the role of interleukin-1beta,
      inducible nitric oxide-synthase and heme oxygenase-1 in D-galactosamine
      sensitized mice.
AB  - OBJECTIVE AND DESIGN: Pretreatment with tumor necrosis factor (TNF)-alpha induces
      tolerance towards itself in experimental liver injury. MATERIAL AND TREATMENT: To
      study mechanisms of TNF tolerance we used knockout mice for either TNF-receptor-2
      (TNFR-2), inducible nitric oxide (NO)-synthase (iNOS) or caspase-1 (ICE) or
      inhibited heme oxygenase-1 (HO-1) by treatment with zinc-protoporphyrin 9. Liver
      damage was induced by administration of TNF to mice sensitized with D
      galactosamine (GalN). Tolerance was induced by pretreatment with low doses of
      TNF. METHODS: Severity of liver injury was assessed by determination of plasma
      transaminases and apoptosis. Time courses of intra-hepatic iNOS, interleukin
      1beta (IL-1beta) and HO-1 expression after TNF treatment were measured by reverse
      transcription polymerase chain reaction (RT-PCR). TNF-receptor-1 (TNFR-1)
      expression was determined by immunofluorescent staining. RESULTS: TNF
      pretreatment did not affect TNFR-1 expression in the liver and resulted in time
      dependent up-regulation of iNOS, IL-1beta and HO-1. TNF- pretreated TNFR-2, iNOS
      or ICE knockout mice were as sensitive towards GalN/TNF as the wild type, while
      mice with impaired HO-1 activity were even more sensitive, but tolerance was
      inducible in all TNF-pretreated mice. CONCLUSIONS: TNF tolerance towards GalN/TNF
      treatment is mediated by TNFR-1. IL-1beta, iNOS and HO-1 neither mediated TNF
      tolerance nor TNF cytotoxicity.

PMID- 12056511
TI  - Tea tree oil reduces the swelling associated with the efferent phase of a contact
      hypersensitivity response.
AB  - OBJECTIVE: To examine the anti-inflammatory activities of tea tree oil (TTO) in
      vivo. METHODS: Mice were sensitized to a chemical hapten, trinitrochlorobenzene,
      on their ventral skin and 7 days later challenged (or re-exposed) on their dorsal
      skin with the same hapten. RESULTS: TTO applied 30 min before or up to 7 h after
      to the same dorsal site as hapten challenge caused a significant reduction in
      skin swelling after 24 h. TTO reduced oedema but not the influx of inflammatory
      cells. This finding was supported by the inability of TTO to suppress TNFalpha
      induced E-selectin expression by human umbilical vein endothelial cells. TTO did
      not suppress irritant- or ultraviolet B-induced oedema. CONCLUSION: Topical TTO,
      specifically the TTO components, terpinen-4-ol and alpha-terpineol can regulate
      the oedema associated with the efferent phase of a contact hypersensitivity
      response.

PMID- 12056512
TI  - Red blood cells stimulate fibroblast-mediated contraction of three dimensional
      collagen gels in co-culture.
AB  - OBJECTIVE AND DESIGN: Following injury, red blood cells (RBC) may interact with
      extracellular matrix (ECM). In the present study we hypothesised that RBC, and
      soluble factors from RBC, might mediate remodelling of ECM by affecting
      fibroblast-mediated contraction of three dimensional collagen gels. MATERIALS AND
      METHODS: Human lung fibroblasts (HFL-1), were cultured together with isolated
      RBC, conditioned medium from RBC (RBC-CM) and hemolysed RBC in type I collagen
      gels. Gel contraction was determined by an image analyser. RESULTS: Both RBC, RBC
      CM and hemolysed RBC stimulated gel contraction by fibroblasts (P < 0.001),
      compared to fibroblasts alone. The RBC-CM stimulated (P < 0.01) gel contraction
      in a time and concentration dependent manner. A similar effect was observed when
      supernatant from hemolysed RBC was tested. The production of fibronectin was
      increased (P < 0.01) in the co-culture system, compared to fibroblasts cultured
      alone. CONCLUSIONS: The present study shows that RBC can interact with
      mesenchymal cells in vitro. The ability of RBC to modulate fibroblast-mediated
      contraction in vitro, might therefore be an important mechanism regulating repair
      processes after injury.

PMID- 12056514
TI  - Differential effects of amphotericin B and liposomal amphotericin B on
      inflammatory cells in vitro.
AB  - OBJECTIVE AND DESIGN: To understand whether the pseudo-allergic reactions to
      amphotericin B (AmB) administration are due to AmB or to the solubilizing
      vehicles, a study was designed to evaluate the effects of AmB, liposomal AmB, (L
      AmB), AmB-deoxycholate micellar complex (AmB-DC) and deoxycholate (DC) on the
      responses of rat serosal mast cells (RSMC) and of human basophils (HB), in vitro.
      MATERIALS AND METHODS: Serosal mast cells were obtained by density gradient
      centrifugations from male Wistar albino rats. Partially purified HB were obtained
      from healthy donors. The cells were exposed to AmB, L-AmB, AmB-DC and DC.
      Histamine release was measured fluorometrically, and the release of lactic
      dehydrogenase (LDH) was measured spectrophotometrically. HB activation was
      evaluated cytofluorimetrically by CD63 expression. RESULTS: AmB and L-AmB did not
      evoke histamine or LDH release from either RSMC or HB. CD63 expression was not
      induced in HB challenged with AmB and L-AMB. On the other hand, AmB-DC and DC
      produced a cytotoxic histamine release from both RSMC and HB, and a sustained
      increase of CD63 expression on HB. CONCLUSIONS: Only AmB-DC was able to induce
      the release of inflammatory mediators from RSMC and HB. Conceivably, the
      cytotoxic effect is accounted for by the micellar complexes with DC, which has
      been confirmed as a powerful histamine releaser, and held responsible for the
      pseudo-allergic reactions after AmB-DC administration. The data lend support to a
      better safety profile of L-AmB.

PMID- 12056513
TI  - Amelioration of rat adjuvant arthritis by therapeutic treatment with bindarit, an
      inhibitor of MCP-1 and TNF-alpha production.
AB  - OBJECTIVE: This study was designed to evaluate therapeutic effects of bindarit,
      an indazolic derivative able to inhibit monocyte chemoattractant protein-1 (MCP
      1) production, in adjuvant induced arthritis in rats. MATERIALS AND METHODS:
      Arthritis was induced by Freund's complete adjuvant injection. Bindarit was given
      as a 0.5% medicated diet starting on day 11 after adjuvant injection. The course
      of arthritis was monitored by sequential paw volume measurement and by radiologic
      and histologic evaluations. Human osteoblast cell line Saos-2 stimulated with
      Interleukin-1 (IL-1) was used to assess in vitro bindarit effect on MCP-1
      release. In addition, in vivo effects of bindarit on cytokine production were
      studied in mice injected with lipopolysaccharide (LPS). Immune function studies
      were performed in mice by evaluating ex vivo antibody response to ovalbumin and
      splenocytes proliferation to Concanavalin A (Con A). RESULTS: In adjuvant-induced
      arthritis in rats, bindarit possessed therapeutic activity resulting in a
      significant inhibition of paw inflammation. Evidence for a disease-modifying
      activity was also indicated by amelioration of radiologic alterations and by
      histological evaluation of joints. Additional evidence for beneficial effects in
      osseous inflammation was provided by an in vitro assay in which bindarit
      inhibited the release of MCP-1 from IL-1 stimulated osteoblast cells. Moreover,
      in a murine model of LPS-induced cytokine production bindarit reduced MCP-1 and
      tumor necrosis factor (TNF)-alpha increase without affecting IL-1 and IL-6
      levels. Finally, the drug, given as a 0.5% medicated diet for 14 days, did not
      affect either anti-ovalbumin serum antibody production or splenocytes
      proliferative response in mice. CONCLUSIONS: Results obtained indicate that
      bindarit beneficial effects in experimental arthritis are correlated to MCP-1 and
      TNF-alpha inhibition and suggest that the control of cytokines and chemokines
      production can have considerable relevance as regards strategies for the
      treatment of chronic inflammatory diseases.

PMID- 12056516
TI  - Nutritional status in peritoneal dialysis: studies in body composition,
      lipoprotein metabolism and peritoneal function.
AB  - This thesis is based on clinical studies including virtually all patients treated
      with peritoneal dialysis in Gothenburg during the 1990s. The patients had a
      fundamentally altered body composition compared to healthy subjects,
      characterised by a reduction in body cell mass and body fat already at start of
      dialysis. During PD treatment. a further decrease in body cell mass was observed.
      Energy stores tended to normalise during the first years of treatment and
      remained constant thereafter, or declined subsequently. Extracellular water,
      calculated from the four-compartment model, was increased when patients started
      PD treatment and increased further, in parallel to the reduction in body cell
      mass. These alterations were seen in combination with a normal. or slightly
      reduced, body weight. Standard methods of assessing nutritional status may
      therefore not be valid in the dialysis population. Prediction equations to
      estimate total body water, used in measurements of dialysis adequacy, give
      erroneous results in PD patients, as shown in a study on our PD population. This
      may have important clinical consequences, especially in wasted patients. Reduced
      muscle mass is a marker of protein-energy malnutrition, and therefore simple and
      reliable methods to measure muscle mass are warranted. When lean body mass was
      calculated from creatinine generation rate and compared to lean body mass
      estimated from measurements of total body potassium. the agreement between the
      two methods was low. Furthermore, when repeated measurements of creatinine
      generation rate were performed, the variation coefficient was unacceptably high.
      Thus. creatinine generation rate cannot be recommended as a method to evaluate
      somatic protein status in PD patients. The lipoprotein metabolic derangements are
      pronounced in PD patients. in which a further increase in cholesterol and
      cholesterol-rich apoB-containing lipoproteins are added to the already pre
      existing renal dyslipidemia. characterised by increased concentration of
      triglycerides and triglyceride-rich complex lipoproteins. There are indications
      that dialytic variables may influence this development. When peritoneal function
      was assessed by the Peritoneal Dialysis Capacity test at start of dialysis, it
      was observed that peritoneal function reflected patient characteristics and co
      morbidity. Patients with systemic disease had enhanced diffusion capacity
      compared to patients with primary renal disorders. Furthermore, in patients with
      more severe co-morbidity. peritoneal protein losses were increased. Finally,
      elderly patients had ultrafiltration conditions that were different from those of
      younger patients. Peritoneal function remained essentially stable during medium
      long term follow up. Body composition features in dialysis patients are similar
      to those seen in severe disease in general. Thus, it is difficult to separate the
      effects of malnutrition from the effects of the underlying disease. Specific
      standards for nutritional status adapted for patients with renal failure are
      required.

PMID- 12056515
TI  - Pneumonia in multiple injured patients: a prospective controlled trial on early
      prediction using clinical and immunological parameters.
AB  - OBJECTIVE AND DESIGN: In a prospective trial 266 multiple injured patients were
      included to evaluate clinical risk factors and immune parameters related to
      pneumonia. METHODS: Clinical and humoral parameters were assessed and
      multivariate analysis performed. RESULTS: The multivariate analysis (odds ratio
      with 95% confidence interval (CI)) revealed male gender (3.65), traumatic brain
      injury (TBI) (2.52), thorax trauma (AIS(thorax) > or = 3) (2.05), antibiotic
      prophylaxis (1.30), injury severity score (ISS) (1.03 per ISS point) and the age
      (1.02 per year) as risk factors for pneumonia. The main pathogens were
      Acinetobacter Baumannii (40%) and Staphylococcus aureus (25%). A tendency towards
      higher Procalcitonin (PCT) and Interleukin (IL)-6 levels two days after trauma
      was observed for pneumonia patients. CONCLUSION: The immune parameters (PCT, IL
      6, IL-10, soluble tumor necrosis factor p-55 and p-75) could not confirm the
      diagnosis of pneumonia earlier than the clinical parameters.

PMID- 12056517
TI  - Demonstration of apoptosis in human skin injuries as an indicator of vital
      reaction.
AB  - Demonstrating the vital character of an injury and estimation of the age are
      routine tasks in forensic pathology and although many different techniques have
      been applied to this problem none have been found to be completely satisfactory.
      Apoptosis, an active genetically controlled process, is the major mechanism by
      which homeostasis of a number of physiological systems in the body is regulated
      and changes in the rate following different kinds of stimuli have prompted us to
      test it as an indicator of vitality. We used an in situ end-labelling technique
      (Apop-Tag) in 30 human surgical skin injuries with age since injury ranging from
      3 min to 8 h and found that apoptotic keratinocytes are found in over 50% of the
      cases with a post-infliction interval of at least 120 min. Apoptosis was not seen
      in injuries less than 120 min old or in normal skin, which was used as an
      external control. These results suggest that apoptosis could be a useful
      indicator for the intravital occurrence of injuries and could help to estimate
      the date of the skin injuries in some cases. The importance of strict technical
      control is stressed and the necessity of a complementary technique to confirm
      apoptosis is discussed.

PMID- 12056518
TI  - Autoerotic accident associated with self-applied ketamine.
AB  - We present a rare case of an autoerotic accident involving a fatal combination of
      asphyxia by suffocation and intoxication with self-administered intravenous
      ketamine. Of note in this case is the fact that the victim was an emergency
      medical technician. Ketamine causes complete analgesia with superficial
      unconciousness and amnesia called "dissociative anasthesia". Futhermore low
      anaesthetic doses of ketamine induce alterations in mood, cognition and body
      image and the substance is an emerging drug of abuse. We discuss the death scene
      investigation, findings at autopsy and the toxicological report.

PMID- 12056519
TI  - Rare failures in the amelogenin sex test.
AB  - Determination of sex using the amelogenin sex test is well established in the
      forensic field especially for casework and DNA databasing purposes. The sex test
      is part of commercially available PCR kits. Among 29,432 phenotypic male
      individuals stored in the Austrian National DNA database, 6 individuals were
      found to lack the amelogenin Y-specific PCR product which was confirmed using
      alternative amelogenin primers. The amplification of eight Y-chromosomal STR
      markers resulted in full profiles in five out of the six samples, one sample
      failed to amplify Y-STRs at all. The amplification of a fragment of the SRY gene
      gave positive results in all six samples, confirming the male phenotype of the
      individuals. The observed failure rate of the amelogenin sex test was 0.018% in
      this study.

PMID- 12056520
TI  - Is the amelogenin gene reliable for gender identification in forensic casework
      and prenatal diagnosis?
AB  - In humans, the amelogenin gene is present on both the X and the Y chromosomes.
      However, there are size differences in this gene between these chromosomes, which
      have been utilised for sexing in forensic casework and prenatal diagnosis. Our
      study using the AmpFl STR Profiler Plus kit, showed a deletion of Y chromosome
      specific amelogenin in five Indian males (1.85%). We propose to call them
      "deleted-amelogenin males" (DAMs), who but for the detection of the presence of
      other Y-specific markers (e.g. SRY, STR and 50f2) would have been identified as
      females. Considering the consequences of the result obtained only using the
      amelogenin marker, we suggest the use of additional Y chromosome markers for
      unambiguous gender identification.

PMID- 12056521
TI  - Is the amelogenin sex test valid?

PMID- 12056522
TI  - Power of exclusion revisited: probability of excluding relatives of the true
      father from paternity.
AB  - In parentage testing using DNA markers, the formulae for calculating the
      probability of exclusion generally overstate the power of a test battery by
      considering its ability to exclude a random man. It is known that in many cases,
      in particular immigration applications, the false father is more likely to be a
      relative, e.g. brother, of the true father than an unrelated man. This work
      presents formulae that take this consideration into account. A practical example
      using Hong Kong data is provided to illustrate the effect of the modification.
      Also discussed is how the expected efficacy of a test battery will be affected
      when possible mutations and null alleles or genetic inconsistencies are taken
      into consideration.

PMID- 12056523
TI  - A new database of mitochondrial DNA hypervariable regions I and II sequences from
      162 Japanese individuals.
AB  - A database of mitochondrial DNA (mtDNA) hypervariable region 1 (HV1) and region 2
      (HV2) sequences of the mtDNA control region was established from 162 unrelated
      Japanese individuals. The random match probability and the genetic diversity for
      this database were 0.96% and 0.997, respectively. Length heteroplasmy in the C
      stretch regions located around position 16189 in HVI and 310 in HV2 was observed
      in 37% and 38% of the samples, respectively. A strategy using internal sequencing
      primers was devised to obtain confirmed sequences in these length heteroplasmic
      individuals. This database, combined with other mtDNA sequence databases from the
      Japanese population, will permit the significance of mtDNA match results to be
      properly reported in mtDNA typing casework in Japan.

PMID- 12056524
TI  - Polymorphism in the mitochondrial cytochrome B gene in Koreans. An additional
      marker for individual identification.
AB  - Sequencing the mitochondrial control region is very useful for individual
      identification when conventional DNA typing using autosomal STRs is unavailable.
      However, low discriminatory power is a problem and another polymorphic locus
      within the mitochondrial genome is necessary. The cytochrome B (MTCYB) gene,
      which has undergone several changes during evolution, may be a good candidate for
      this purpose. Here the sequencing data of the MTCYB gene of 98 unrelated Koreans
      is presented. A total of 30 polymorphic sites were found which were distributed
      evenly along the gene. All were nucleotide substitutions and no
      insertions/deletions were noted. A total of 22 different MTCYB lineages were
      revealed. Out of 22 different control region lineages with 79 samples which
      shared the same D-loop sequence with some others within a lineage, 10 lineages
      with 37 samples could be sub-grouped according to different MTCYB sequences. Some
      issues concerning the MTCYB gene polymorphism are discussed.

PMID- 12056525
TI  - The statistical evaluation of DNA mixtures with contributors from different
      ethnic groups.
AB  - The effect of a structured population on the evaluation of forensic mixed stains
      has been considered by the authors and others. However, in countries with
      multiple racial or ethnic groups, it is not uncommon that contributors to a DNA
      mixture are of different ethnic groups. A famous example is the OJ Simpson case
      in which the suspect was an African-American, the victims were Caucasian
      Americans and the true perpetrator(s) could be from any ethnic group(s). In this
      paper six common mixture cases are considered and the formulae for likelihood
      ratios are derived. These formulae can help forensic DNA scientists acquire a
      better understanding of the problem. The effect of different ethnic groups is
      illustrated using a case in Hong Kong.

PMID- 12056526
TI  - Immunohistochemical detection of chemokines in human skin wounds and its
      application to wound age determination.
AB  - Immunohistochemical studies on the time-dependent expression of the chemokines
      such as interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and
      macrophage inflammatory protein (MIP)-1alpha were performed on 50 human skin
      wounds with different wound ages (group I 0-12 h, group II 1-4 days, group III 7
      14 days and group IV 17-21 days). In the wound specimens with wound ages between
      4 and 12 h, neutrophils mainly showed positive reactions for IL-8, MCP-1 and MIP
      1alpha. With increasing wound ages, macrophages and fibroblasts were positively
      stained with anti-IL-8, MIP-1alpha and MCP-1 antibodies. Morphometrically, there
      was a similar distribution in the positive ratios of the inflammatory cells among
      IL-8, MCP-1 and MIP-alpha. The positive ratios of each chemokine were very low in
      group I and a considerable increase of the positive ratios in each chemokine was
      observed in group II (mean +/- standard error IL-8: 59.8 +/- 2.1%, MCP-1: 42.4 +/
      3.1% and MIP-1alpha: 50.4 +/- 3.7%). Although the positive ratios for each
      chemokine gradually decreased according to the wound age, the mean positive
      ratios in groups III and IV were significantly higher than those in group I. From
      the forensic aspect, these chemokines are considered useful markers for wound age
      determination. Thus, ratios of > 50% for IL-8, > 30% for MCP-1 or > 40% for MIP
      1alpha indicate a wound age of at least I day. Moreover, the combined
      investigation of these three chemokines can make wound age determination more
      objective and accurate.

PMID- 12056528
TI  - Continental and subcontinental distributions of mtDNA control region types.
AB  - When the mtDNA profile of a crime scene matches that of a suspect, it is
      necessary to determine the probability of a chance match by consulting the
      frequencies of the identified allele in a "reference population". The ceiling
      principle suggests that that population should be chosen in which the allele of
      the suspect is found at the highest frequency, in order to give the suspect the
      maximum benefit of doubt. Recently, we advocated the use of a worldwide
      mitochondrial database combined with a geographical information system to
      identify the regions of the world with the highest frequencies of matching mtDNA
      types. Here, we demonstrate that the alternative approach of defining a ceiling
      reference population on the basis of continent or phenotype (race) is too coarse
      for a non-negligible percentage of mtDNA control region types.

PMID- 12056527
TI  - Induction of apolipoprotein E after traumatic brain injury in forensic autopsy
      cases.
AB  - We investigated the dynamics of the induction of apolipoprotein E (apoE) in the
      human brain after death caused by traumatic brain injury (TBI). A striking
      difference in apoE immunoreactivity in the traumatised cortical hemisphere
      compared with the contralateral non-traumatised hemisphere was observed. ApoE was
      detected within the neurons of the traumatised cortical hemisphere in cases
      surviving only about 2 h, as well as in those surviving for extended periods. In
      contrast, no apoE staining within the neurons was seen in the contralateral
      cortical hemisphere. ApoE staining within astrocytes was faint in both
      traumatised and contralateral hemispheres of cases surviving only 2 h. However,
      staining was intense in the traumatised hemispheres in short as well as long
      surviving cases, even those surviving more than 1 month. ApoE immunoreactivity
      was also observed in areas adjacent to capillaries and surrounding the neuropil
      of the injured hemisphere. These observations corroborated the idea of a
      prolonged induction of apoE within the neurons and also in the extracellular
      matrix after TBI. Furthermore, the possibility is suggested that the alteration
      of apoE distribution may contribute to a cerebroprotective mechanism immediately
      after TBI.

PMID- 12056530
TI  - Fast- and slow-release tablets for oral administration of flavonoids: rutin and
      quercetin.
AB  - Many derivatives of rutin (Rt) and its metabolite quercetin (Q) are employed in
      clinics for cardiovascular chronic pathology, and are also known for their
      antiulcer behavior in vivo and antiproliferative and antimutagenic activity in
      vitro. Unfortunately, the absorption of quercetin and rutin from the
      gastrointestinal tract is slow and irregular, probably due to their very slight
      solubility in water and slow dissolution rate. In this work the dissolution rate
      of the drugs from oral formulations has been improved using some enhancers such
      as cross-linked sodium carboxy, methylcellulose (CMC-XL), sodium
      carboxymethylstarch (E), and cross-linked polyvinylpyrrolidone (P). The drugs
      were loaded on the hydrophilic carriers by different techniques such as mixing or
      co-milling. The in vitro dissolution profiles of the mixed or co-milled
      drug/polymer systems, obtained in various media with different pH, were compared.
      The results show that the drug dissolution rate from the co-milled drug/carrier
      systems is faster than that from mixed systems, and CMC-XL and sodium
      carboxymethylstarch systems are able to enhance the dissolution rate. For this
      reason, these co-milled drug/carrier systems were used for the production of both
      fast- and slow-release tablets. The co-milled drug/CMC-XL system was used for the
      preparation of fast-release tablets containing rutin, while three different fast
      release tablets were formulated and tested using respectively Q/CMC-XL, Q/E, and
      Q/P co-milled systems. The effect of the presence of sodium lauryl sulfate in the
      aqueous medium on the dissolution profile of flavonoids alone was also studied.
      The prolonged-release formulations have been developed using
      hydroxypropylmethylcellulose (HPMC) of different viscosity grades as retarding
      polymer. An extended release of the drugs for times ranging from 6 to 14 hr could
      be obtained, depending on the type and viscosity of the HPMC used.

PMID- 12056529
TI  - Penetration enhancers and ocular bioadhesives: two new avenues for ophthalmic
      drug delivery.
AB  - This review is focused on the two avenues of development that promise a major
      impact on future ocular drug therapeutics: bioadhesives, including hydrogels and
      other agents like carbopols, polyacrylic acids, chitosan, etc., and penetration
      enhancers, including different surfactants, calcium chelators, etc. The capacity
      of some polymers to adhere to the mucin coat covering the conjunctiva and the
      corneal surface of the eye forms the basis for ocular mucoadhesion. These systems
      markedly prolong the residence time of a drug in the conjunctival sac, since
      clearence is now controlled by the much slower rate of mucus turnover rather than
      the tear turnover rate. But improving the corneal drug retention alone is
      inadequate in bringing about a significant improvement of drug bioavailability.
      Another approach consists of transiently increasing the pentration
      characteristics of the cornea with appropriate substances, known as penetration
      enhancers or absorption promoters. The main aim of this article is to give an
      insight into the potential application of mucoadhesives and corneal penetration
      enhancers for the conception of innovative opthalmic delivery appraoches, to
      decrease the systemic side effects, and create a more focused effect, which may
      be achieved with lower doses of the drug. Ophthalmic formulations based on these
      mucoadhesives and penetration enhancers are simple to manufacture and exhibit an
      excellent tolerance when administered into the cornea. The use of the former
      considerably prolongs the corneal contact time and the use of the latter
      increases the rate and amount of drug transport. The various corneal epithelial
      barriers along with the major routes of transport of drugs are discussed. The
      article includes a list of the various substances in use or under investigation
      for the aforementioned properties, along with their mechanisms of action. A fair
      appraisal of the subject with regard to these two therapeutic approaches and any
      expected ill effects has been made.

PMID- 12056531
TI  - Synthesis and evaluation of rosin-based polymers as film coating materials.
AB  - Rosin-based polymers (R-1 and R-2) were synthesized and characterized for
      physicochemical properties, molecular weight (Mw), polydispersity (Mw/Mn), glass
      transition temperature (Tg), and thermogravimetry (TGA). Films of the polymers
      were cast on a mercury substrate by solvent evaporation technique. Free films
      were characterized for surface topography by scanning electron microscopy (SEM),
      water vapor transmission rate (WVTR), tensile strength, percentage elongation,
      and modulus of elasticity. The polymers were further evaluated as film coating
      materials by evaluating drug release from coated pellets with diclofenac sodium
      as a model drug. Drug was loaded on non-pareil seeds by a solution-layering
      technique and coated with varying concentrations of polymer solutions. Sustained
      release of the drug was observed from coated pellets. The newly synthesized rosin
      based polymers promise considerable utility for pharmaceutical coating.

PMID- 12056533
TI  - Plasticizer effect and comparative evaluation of cellulose acetate and
      ethylcellulose-HPMC combination coatings as semipermeable membranes for oral
      osmotic pumps of naproxen sodium.
AB  - The objective of this study was to compare the performance of cellulose acetate
      (CA) and ethylcellulose (EC)-HPMC combination coatings as semipermeable membranes
      (SPMs) for osmotic pump tablets (OPTs) of naproxen sodium (NPS) so as to deliver
      a constant, predetermined amount of drug in solution form over a fixed span of
      time, independent of external environmental conditions. Osmotic pump tablets were
      designed with different coating variables and optimized in terms of nature of
      plasticizer, membrane thickness, and orifice diameter. The effect of insertion of
      an inner microporous film around the NPS core to minimize deformation of the SPM
      due to peristaltic movement of the gut was also studied. Osmotic pump tablets
      composed of membranes with water-soluble plasticizer, propyleneglycol (PG),
      released drug mainly through diffusion, whereas those designed with CA and EC
      HPMC (4:1) coats containing water-insoluble plasticizer, castor oil, released
      their contents by perfect zero-order kinetics over a prolonged period of time,
      though the average release rate that could be achieved with the EC-HPMC (4:1)
      membrane was only about half the rate achieved with the CA membrane for the same
      membrane thickness. Release rates for both the membranes decreased with
      increasing membrane thickness and were found to be independent of orifice
      diameter, agitation intensity, and pH of the dissolution medium.

PMID- 12056532
TI  - Evaluation of the film-coating properties of a hydroxyethyl
      cellulose/hydroxypropyl methylcellulose polymer system.
AB  - The effect of different grades of hydroxyethyl cellulose (HEC) and hydroxypropyl
      methllcellulose (HPMC) on the film-formation and taste-masking ability for
      ibuprofen granules was evaluated. Three batches of coated ibuprofen granules were
      prepared using a roto-granulator, each with a different coating composition. Two
      grades of HEC [MW300,000 (H) and MW90,000 (L)] were combined with three different
      grades of HPMC [MW 11,000 (L), MW 25,000 (M) and MW 35,000 (H)] to prepare the
      coating solutions. Mechanical strength and physical properties of the polymer
      films were evaluated. Films made from HPMC (L)/HEC (H), HPMC (M)/HEC (H), and
      HPMC (H)/HEC (H) were stronger and more flexible than the HPMC (L) HEC (L) films.
      The assay, dissolution, particle size distribution, and environmental scanning
      electron microscopy (ESEM) data of the three batches of the coated ibuprofen
      granules were similar.

PMID- 12056535
TI  - Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay)
      in healthy human volunteers.
AB  - An open, randomized, two-way crossover study was carried out in 28 healthy
      volunteers at Gulf Pharmaceutical Industries (Julphar), as a joint venture with
      Saqr Hospital, Ras Al-Khaimah, UAE. The two commercial brands used were Sarf
      (Julphar, UAE) as test and Ciprobay (Bayer AG, Germany) as reference product. The
      drug was administered to each subject with 240 mL of water after an overnight
      fasting in two treatment days separated by a one-week washout period. After
      dosing, serial blood samples were collected for a period of 24 hr and serum was
      separated and analyzed for ciprofloxacin using a sensitive, reproducible, and
      accurate high-performance liquid chromatography (HPLC) method with ultraviolet
      (UV) detection. Various pharmacokinetic parameters, including AUC0-t, AUC0
      infinity, Cmax, Tmax, t1/2, and lambdaz, were determined from ciprofloxacin serum
      concentration-time profiles for both formulations and found to be in good
      agreement with reported values. The parameters AUC0-t, AUC0-infinity, and Cmax
      were tested for bioequivalence after log-transformation of data. No significant
      difference was found based on analysis of variance (ANOVA); the 90% confidence
      intervals (95.73-107.62%, 94.98-108.26%, 92.80-103.90% for AUC0-t, AUC0-infinity,
      Cmax, respectively) for the test/reference ratios of these parameters were within
      the bioequivalence acceptance range of 80-125%. Based on this data, it is
      concluded that both formulations are bioequivalent and are interchangeable in
      medical practice.

PMID- 12056534
TI  - Stability study of flutamide in solid state and in aqueous solution.
AB  - A high-performance liquid chromatography (HPLC) assay has been developed for the
      determination of flutamide and its degradation products. Using this method, the
      influence of important formulation factors on the stability of flutamide has been
      estimated. The stability studies have been carried out in solid state as well as
      in aqueous solution. The results obtained have shown a good stability for
      flutamide in solid state. This drug remained practically unchanged after a four
      month assay in adverse temperature and humidity conditions. On the other hand,
      the results obtained from the stability study in solution during 12 days have
      shown that flutamide in aqueous solution underwent a clear degradation at mean or
      high temperature (22 degrees C, 37 degrees C) and acidic pH conditions (1.1).
      With respect to the influence of ionic strength, it has been found that the
      presence of sodium chloride prevents the degradation of flutamide in aqueous
      solution. The second-order kinetics model provides the best fit for highly
      degraded solutions.

PMID- 12056536
TI  - Development of controlled-release buccoadhesive hydrophilic matrices of diltiazem
      hydrochloride: optimization of bioadhesion, dissolution, and diffusion
      parameters.
AB  - Buccoadhesives have long been employed to improve the bioavailability of drugs
      undergoing significant hepatic first-pass metabolism. Diltiazem hydrochloride
      (DLZ) is also reported to have low oral bioavailability due to an extensive
      hepatic first-pass effect. Controlled-release buccoadhesive hydrophilic matrices
      containing DLZ were prepared using a 3(2) factorial design. Amounts of Carbopol
      934P (CP) and Methocel K100LV (HPMC) were taken as the formulation variables
      (factors) for optimizing bioadhesion, and kinetics of dissolution and diffusion.
      A mathematical model was generated for each response parameter. Bioadhesive
      strength tended to vary quite linearly in increasing order with increasing amount
      of each polymer. The drug release pattern for all the formulation combinations
      was found to be non-fickian, approaching zero-order kinetics. The values of
      permeation coefficient tended to vary non-linearly with polymer amount, depicting
      the plausibility of interaction between the two polymers. Suitable combinations
      of the two polymers provided adequate bioadhesive strength and a fairly regulated
      release profile up to 10 hr. The response surfaces and contour plots for each
      response parameter are presented for further interpretation of the results. The
      optimum formulations were chosen and their predicted results found to be in close
      agreement with experimental findings.

PMID- 12056538
TI  - Effect of microcrystalline cellulose grade and process variables on pellets
      prepared by extrusion-spheronization.
AB  - This study evaluated the effects of spheronizer load and speed on the size,
      circularity, microporosity, compressibility, and friability of pellets prepared
      by extrusion-spheronization of wet microcrystalline cellulose (MCC) masses with a
      water content shown by mixer torque rheometry to ensure maximum consistency. Two
      MCC grades with different mean particle size were used. Both gave pellets with
      good particle size, sphericity, and compressibility, under a wide range of
      spheronization conditions. Modification of pellet properties of interest
      (including size and porosity) was possible by adjustment of spheronization
      conditions and MCC grade; in particular, pellet porosity was greater with MCC of
      larger particle size.

PMID- 12056537
TI  - Application of hydroalcoholic solutions of formaldehyde in preparation of
      acetylsalicylic acid gastro-resistant capsules.
AB  - Enteric coating of hard gelatin capsules by application of hydroalcoholic
      solutions of formaldehyde was studied and developed in accordance with previous
      publications. It is possible to affirm that this coating constitutes a simple,
      stable, reproducible, and inexpensive method, being a valid alternative to those
      which have been proposed. The aim of the present investigation is the preparation
      of acetylsalicylic acid gelatin capsules with good conditions of gastro
      resistance and enteros solubility.

PMID- 12056539
TI  - Investigation of the effect of tablet surface area/volume on drug release from
      hydroxypropylmethylcellulose controlled-release matrix tablets.
AB  - The purpose of this study was to investigate the influence of tablet surface
      area/volume (SA/Vol) on drug release from controlled-release matrix tablets
      containing hydroxypropylmethylcellulose (HPMC). Soluble drugs (promethazine HCl,
      diphenhydramine HCl, and propranolol HCl) were utilized in this study to give
      predominantly diffusion-controlled release. Drug release from HPMC matrix tablets
      with similar values of SA/Vol was comparable within the same tablet shape (i.e.,
      flat-faced round tablets) and among different shapes (i.e., oval, round concave,
      flat-faced beveled-edge, and flat-faced round tablets). Tablets having the same
      surface area but different SA/Vol values did not result in similar drug release;
      tablets with larger SA/Vol values hadfaster release profiles. Utility of SA/Vol
      to affect drug release was demonstrated by changing drug doses, and altering
      tablet shape to adjust SA/Vol. When SA/Vol was held constant, similar release
      profiles were obtained with f2 metric values greater than 70. Thus, surface
      area/volume is one of the key variables in controlling drug release from HPMC
      matrix tablets. Proper use of this variable has practical application by
      formulators who may need to duplicate drug release profiles from tablets of
      different sizes and different shapes.

PMID- 12056540
TI  - Weight and weight uniformity of hard gelatin capsules filled with
      microcrystalline cellulose and silicified microcrystalline cellulose.
AB  - The objective of this study was to investigate the weight and weight uniformity
      of hard gelatin capsules filled with microcrystalline cellulose (MCC) and
      silicified microcrystalline cellulose (SMCC) powdered formulations. A tamping
      type encapsulation apparatus was used to fill the capsules. The four formulations
      that were tested included MCC alone, MCC blended with fumed silica, SMCC, and
      high-density SMCC (SMCC-HD). The mean capsule weight and the average variation in
      mean capsule weight of each formulation were determined. Both SMCC products
      exhibited better flow than the MCC alone, with SMCC-HD being the freest flowing
      of the powders investigated. Capsules filled with the SMCC products had higher
      fill weights than those containing the MCC powders. The SMCC-containing capsules
      exhibited the lowest variation in weight, although these findings were not
      significantly different from either of the MCC-containing capsules. Significantly
      higher weight variations were found in capsules filled with SMCC-HD. A
      relationship between Carr's compressibility index and capsule weight variation
      was found, with more compressible materials producing more uniformly filled
      capsules. No relationship could be established between powder flow and capsule
      weight uniformity. These findings suggest that powder flow may not be a critical
      parameter in ensuring capsule weight uniformity when the encapsulation equipment
      utilizes a tamping-type filling system.

PMID- 12056541
TI  - Discovery of recently adopted orphan receptors for apelin, urotensin II, and
      ghrelin identified using novel radioligands and functional role in the human
      cardiovascular system.
AB  - Using novel synthetic radioligands, we have discovered receptors for the recently
      paired apelin (APJ orphan receptor), ghrelin (GHS orphan receptor), and urotensin
      II (orphan GPR14) in the human cardiovascular system and determined their
      anatomical localisation. In addition, we have established functional vasoactive
      properties for these three peptides as potential vasoconstrictor/vasodilator
      mediators and provided evidence for alteration of receptor density in
      cardiovascular disease. We find that receptors for apelin, ghrelin, and urotensin
      II are widely distributed in human cardiovascular tissue, suggesting perhaps
      vasoactive roles for these peptides in human vascular physiology and a potential
      role in pathophysiology. Apelin and urotensin II are potent vasoconstrictors with
      low efficacy, consistent with their low receptor density. Ghrelin receptor
      density was increased (approximately three- to fourfold) with atherosclerosis of
      coronary artery disease and accelerated atherosclerosis of saphenous vein grafts,
      compared with normal vessels, highlighting a potentially beneficial role for this
      novel vasodilator peptide in human vascular disease. Our approach has
      demonstrated one successful strategy for translating genetic information encoding
      recently paired orphan receptor ligands into discovery of function. This study
      has the advantage of focussing on the actual disease processes, which allow the
      more precise identification of novel therapeutic targets.

PMID- 12056542
TI  - Activation and targeting of mitogen-activated protein kinases by G-protein
      coupled receptors.
AB  - Over the past decade, it has become apparent that many G-protein-coupled
      receptors (GPCRs) generate signals that control cellular differentiation and
      growth, including stimulation of Ras family GTPases and activation of mitogen
      activated protein (MAP) kinase pathways. The mechanisms that GPCRs use to control
      the activity of MAP kinases vary between receptor and cell type but fall broadly
      into one of three categories: signals initiated by classical G protein effectors,
      e.g., protein kinase (PK)A and PKC, signals initiated by cross-talk between GPCRs
      and classical receptor tyrosine kinases, e.g., "transactivation" of epidermal
      growth factor (EGF) receptors, and signals initiated by direct interaction
      between beta-arrestins and components of the MAP kinase cascade, e.g., beta
      arrestin "scaffolds". While each of these pathways results in increased cellular
      MAP kinase activity, emerging data suggest that they are not functionally
      redundant. MAP kinase activation occurring via PKC-dependent pathways and EGF
      receptor transactivation leads to nuclear translocation of the kinase and
      stimulates cell proliferation, while MAP kinase activation via beta-arrestin
      scaffolds primarily increases cytosolic kinase activity. By controlling the
      spatial and temporal distribution of MAP kinase activity within the cell, the
      consequences of GPCR-stimulated MAP kinase activation may be determined by the
      mechanism by which they are activated.

PMID- 12056543
TI  - NMR studies of CCK-8/CCK1 complex support membrane-associated pathway for ligand
      receptor interaction.
AB  - The interaction of peptide ligands with their associated G-protein-coupled
      receptors has been examined by a number of different experimental approaches over
      the years. We have been developing an approach utilizing high-resolution NMR to
      determine the structural features of the peptide ligand, well-designed fragments
      of the receptor, and the ligand-receptor complexes formed upon titration of the
      peptide hormone. The results from these investigations provide evidence for a
      membrane-associated pathway for the initial interaction of peptide ligands with
      the receptor. Here, our results from the investigation of the interaction of CCK
      8 with the CCK1 receptor are described. Our spectroscopic results clearly show
      that both CCK-8 and the regions of CCK1 with which it interacts are closely
      associated with the zwitterionic interface of the lipids utilized in our solution
      spectroscopic studies.

PMID- 12056544
TI  - Melanin-concentrating hormone and its receptors: state of the art.
AB  - Melanin-concentrating hormone (MCH) is a cyclic neuropeptide of nineteen amino
      acids in mammals. Its involvement in the feeding behaviour has been well
      established during the last few years. A first receptor subtype, now termed
      MCHIR, was discovered in 1999, following the desorphanisation of the SLCI orphan
      receptor, using either reverse pharmacology or systematic screening of agonist
      candidates. A second MCH receptor, MCH2R, has been discovered recently, by
      several groups working on data mining of genomic banks. The molecular
      pharmacology of these two receptors is only described on the basis of the action
      of peptides derived from MCH. The present review tentatively summarizes the
      knowledge on these two receptors and presents the first attempts to discover new
      classes of antagonists that might have major roles in the control of obesity and
      feeding behaviour.

PMID- 12056545
TI  - Peptide signals regulating food intake and energy homeostasis.
AB  - The adiposity hormone leptin has been shown to decrease food intake and body
      weight by acting on neuropeptide circuits in the hypothalamus. However, it is not
      clear how this primary hypothalamic action of leptin is translated into a change
      in food intake. We hypothesize that the behavioral effect of leptin ultimately
      involves the integration of neuronal responses in the forebrain with those in the
      nucleus tractus solitarius in the caudal brainstem, where ingestive behavior
      signals are received from the gastrointestinal system and the blood. One example
      is the peptide cholecystokinin, which is released from the gut following
      ingestion of a meal and acts via vagal afferent nerve fibers to activate medial
      nucleus tractus solitarius neurons and thereby decrease meal size. While it is
      established that leptin acts in the arcuate nucleus in the hypothalamus to
      stimulate anorexigenic neurons that inhibit food intake while simulataneously
      inhibiting orexigenic neurons that increase food intake, the mechanisms linking
      these effects with regions of the caudal brainstem that integrate cues related to
      meal termination are unclear. Based on an increasing body of supportive data, we
      hypothesize that this integration involves a pathway comprising descending
      projections from neurons from the paraventricular nucleus to neurons within the
      nucleus tractus solitarius that are activated by meal-related satiety factors.
      Leptin's anorexic effect comprises primarily decreased meal size, and at
      subthreshold doses for eliciting an effect on food intake, leptin intensifies the
      satiety response to circulating cholecystokinin. The location of neurons
      subserving the effects of intracerebroventricular administration of leptin and
      intraperitoneal injection of cholecystokinin on food intake has been identified
      by analysis of Fos expression. These studies reveal a distribution that includes
      the paraventricular nucleus and regions within the caudal brainstem, with the
      medial nucleus tractus solitarius having the most pronounced Fos expression in
      response to leptin and cholecystokinin, and support the hypothesis that the long
      term adiposity signal leptin and the short-term satiety signal cholecystokinin
      act in concert to maintain body weight homeostasis.

PMID- 12056546
TI  - Effects of naloxone benzoylhydrazone on native and recombinant
      nociceptin/orphanin FQ receptors.
AB  - We have studied the effects of naloxone benzoylhydrazone (NalBzoH) at recombinant
      human OP4 receptors expressed in Chinese hamster ovary (CHO) cells (CHOhOP4) and
      native OP4 sites in isolated tissues from various species. In CHOhOP4 membranes,
      nociceptin (NC) and NalBzoH displaced [125I]Tyr14-NC with pKi values of 10.1 and
      7.3. In the presence of 100 microM GDP, NC stimulated GTPgamma35S binding (pEC50
      = 8.5). NalBzoH was ineffective but antagonized the effects of NC (pA2 = 6.9). At
      5 microM GDP, there was an increase in potency (pEC50 = 9.3) and efficacy (4.3
      fold) of NC. NalBzOH was a partial agonist (pEC50 = 7.0, Emax = 13% relative to
      NC). In CHOhOP4 cells, NC and NalBzoH inhibited cAMP formation with pEC50 and
      Emax values of 9.8 and 100% and 6.0 and 44%, respectively. In the rat vas
      deferens, NalBzoH (10 microM) did not modify electrically induced twitches but
      competitively antagonized the inhibitory action of NC (pA2 = 6.2). In the mouse
      vas deferens (mVD) and guinea pig ileum (gpI), NalBzoH inhibited twitches with
      pEC50 and Emax values of 7.6 and 78% and 8.5 and 77%, respectively. The effect of
      3 microM NalBzoH was fully inhibited by 3 microM naloxone in mVD and 30 microM in
      gpI. Under these conditions, NalBzoH antagonized the actions of NC in both
      preparations with pA2 values of 6.3 and 6.8, respectively. Collectively, these
      data demonstrate that NalBzoH is a nonselective OP4 ligand with system-dependent
      behaviour.

PMID- 12056547
TI  - Interaction of a non-peptide agonist with angiotensin II AT1 receptor mutants.
AB  - To identify residues of the rat AT1A angiotensin II receptor involved with signal
      transduction and binding of the non-peptide agonist L-162,313 (5,7-dimethyl-2
      ethyl-3-[[4-[2(n-butyloxycarbonylsulfonamido)-5-isobutyl-3
      thienyl]phenyl]methyl]imidazol[4,5,6]-pyridine) we have performed ligand binding
      and inositol phosphate turnover assays in COS-7 cells transiently transfected
      with the wild-type and mutant forms of the receptor. Mutant receptors bore
      modifications in the extracellular region: T88H, Y92H, G1961, G196W, and D278E.
      Compound L-162,313 displaced [125I]-Sar1,Leu8-AngII from the mutants G196I and
      G196W with IC50 values similar to that of the wild-type. The affinity was,
      however, slightly affected by the D278E mutation and more significantly by the
      T88H and Y92H mutations. In inositol phosphate turnover assays, the ability of L
      162,313 to trigger the activation cascade was compared with that of angiotensin
      II. These assays showed that the G196W mutant reached a relative maximum
      activation exceeding that of the wild-type receptor; the efficacy was slightly
      reduced in the G1961 mutant and further reduced in the T88H, Y92H, and D278E
      mutants. Our data suggest that residues of the extracellular domain of the AT1
      receptor are involved in the binding of the non-peptide ligand, or in a general
      receptor activation phenomenon that involves conformational modifications for a
      preferential binding of agonists or antagonists.

PMID- 12056548
TI  - Angiotensin II is bound to both receptors AT1 and AT2, parallel to the
      transmembrane domains and in an extended form.
AB  - We have applied photoaffinity labelling methods combined with site-directed
      mutagenesis towards the two principal angiotensin II (AnglI) receptors AT1 and
      AT2 in order to determine contact points between AngII and the two receptors. We
      have first identified the receptor contact points between an N- and a C-terminal
      residue of the AngII molecule and the AT1 receptor and constructed with this
      stereochemical restriction a molecular model of AT1. A similar approach with a
      modified procedure of photoaffinity labelling has allowed us now to determine
      contact points also in the AT2 receptor. Molecular modelling of AT2 on the
      rhodopsin scaffold and energy minimisation of AngII binding into this AT2 model
      produced a model strikingly similar to the AT11 structure. Superposition of the
      experimentally obtained contact points of AngII with AT2 upon this model revealed
      excellent congruence between the experimental and modelling results. CONCLUSIONS:
      (i) athough AT1 and AT2 have quite low sequence homology, they both bind AngII
      with similar affinity and in an almost identical fashion, as if the ligand
      dictates the way it has to be bound, and (ii) in its bound form, AngII adopts an
      extended conformation in both AT1 and AT2, contrary to all previous predictions.

PMID- 12056549
TI  - Relevant role of Leu265 in helix VI of the angiotensin AT1 receptor in agonist
      binding and activity.
AB  - The finding of critical residues for angiotensin II (AII) binding and receptor
      signalling in helices V and VI led us to assess if, in this region of the
      receptor, aliphatic side chains might play a role in the agonist-mediated
      mechanism. Two mutations of the angiotensin AT1 receptor were designed to explore
      a possible role of a leucine at two positions, Leu265 and Leu268. Thus two
      mutants, L265D and L268D, were prepared through single substitutions of Leu265,
      located in the C-terminal region of transmembrane VI (TM-VI), and Leu268, in the
      adjoining region of the third extracellular loop (EC-3), for an aspartyl residue,
      and were stably transfected into Chinese hamster ovary (CHO) cells. Ligand
      binding experiments and the functional assays determining inositol phosphate (IP)
      production were performed in these cells expressing these mutants. No significant
      changes were found in the binding affinity for the ligands, AII, DuP753, and
      [Sar1Leu8]AII in the mutant L268D. Moreover, the relative potency and the maximum
      effect on IP production of this mutant were similar to those of the wild-type
      receptor. In contrast, L265D mutant AT1 receptor, located within the
      transmembrane domain, markedly decreased binding affinity and ability to
      stimulate phosphatidylinositol turnover. Our results suggest that the hydrophobic
      side chain of Leu265, at the C-terminal portion of the AT1's TM-VI, but not
      Leu268, which belongs to the EC-3 loop, might interact with the AII molecule. On
      the other side, the aliphatic side chain of Leu265 may be involved in the
      formation of the ligand binding sites through allosteric effects, thus helping to
      stabilize the receptor structure around the agonist binding site for full
      activity.

PMID- 12056550
TI  - Systemic site of action for pressor effect of angiotensin II injected into the
      fourth cerebral ventricle of rats?
AB  - Angiotensin II (ANG II) causes a systemic pressor effect when injected into the
      cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG
      II pressor effect are over 100 times larger than in the systemic circulation.
      Considering the discrepancy of doses, the possibility that ANG II may reach the
      systemic circulation and promote pressor effects, following injection into the
      fourth ventricle, was investigated. The effects on blood pressure of different
      vasoactive peptides that produce pressor responses when injected into the central
      nervous system were compared. Dose-response curves were obtained for intravenous
      or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP),
      bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for
      intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP,
      0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations,
      pressor responses occurred in the donor rat following injection into the fourth
      cerebral ventricle of the recipient animal, showing that effective doses of ANG
      II, administered to the fourth cerebral, reach the systemic circulation. The same
      results were obtained for the microinjection of 4 nmol of LVP into the fourth
      cerebral ventricle of recipient animals. High-performance reverse-phase liquid
      chromatography analyses of arterial blood showed that approximately 1% of the
      [125I]ANG II injected into the fourth cerebral ventricle may be recovered from
      the systemic circulation a few seconds after the microinjection. The systemic
      administration of the ANG II receptor antagonist losartan blocked the response to
      ANG II injected into the fourth ventricle whereas antagonist administration in
      the same ventricle did not. Angiotensin injections into the lateral ventricle
      produced pressor responses that were reduced by antagonist administration to the
      same ventricle but not by systemic administration of the antagonist. The data
      suggest that the pressor effect resulting from ANG II or LVP injections into the
      fourth cerebral ventricle may be due to the action of this peptide in the
      systemic circulation. On the other hand, the pressor effect due to ANG II
      microinjection into the lateral ventricle apparently results from the direct
      stimulation of central periventricular structures.

PMID- 12056551
TI  - Nonpeptidic endothelin-converting enzyme inhibitors and their potential
      therapeutic applications.
AB  - Endothelins (ETs) are potent vasoconstrictors, promitogens, and inflammatory
      mediators. They have been implicated in the pathogenesis of various
      cardiovascular, renal, pulmonary, and central nervous system diseases. Since the
      final step of the biosynthesis of ETs is catalyzed by a family of endothelin
      converting enzymes (ECEs), inhibitors of these enzymes may represent novel
      therapeutic agents. Currently, seven isoforms of these metalloproteases have been
      identified; they all share a significant amino acid sequence identity with
      neutral endopeptidase 24.11 (NEP), another metalloprotease. Therefore, it is not
      surprising that the majority of ECE inhibitors also possess potent NEP inhibitory
      activity. To date, three classes of ECE inhibitors have been synthesized: dual
      ECE/NEP inhibitors, triple ECE/NEP/ACE inhibitors, and selective ECE inhibitors.
      Potential clinical applications of these compounds in hypertension, chronic heart
      failure, restenosis, renal failure, and cerebral vasospasm deduced from studies
      with relevant animal models are reviewed.

PMID- 12056552
TI  - Inhibition of endothelin-converting enzyme for protection against neointimal
      proliferation following balloon angioplasty of the rat carotid artery.
AB  - Clinical success of percutaneous transluminal coronary angioplasty is limited by
      restenosis within months of the initial intervention. A number of vasoactive
      mediators and growth factors have been reported to participate in this process.
      The aim of the present experiments was to examine the effects of nonselective
      neutral endopeptidase (NEPi)/endothelin-converting enzyme (ECEi) inhibitors
      against neointimal proliferation (NIP) following balloon angioplasty of the left
      carotid artery of Sprague-Dawley rats with the right vessel serving as the
      uninjured control. The rats were divided in several groups: group 1, nontreated
      (vehicle); group 2, treated with a selective NEPi i.p.; groups 3-7, treated with
      nonselective NEPi/ECEi either i.p., s.c., i.v., or p.o. at various doses. After 2
      weeks, cross-sectional histopathological and morphometrical examination of the
      left carotids revealed a severe NIP in vehicle-treated angioplastic rats compared
      with the control uninjured right carotid of the same rats. The selective NEPi CGS
      24592 had no significant effect on restenosis, nor did the dual NEPi/ECEi CGS
      26303 at 5 mg x kg(-1) x day(-1) i.p. Both s.c and i.v. NEPi/ECEi treatment (10
      mg x kg(-1) x day(-1) b.i.d. s.c. or 10 mg x kg(-1) x day(-1) i.v.) reduced NIP
      by up to 35%. The prodrug CGS 26393 (p.o.) also attenuated NIP by 23%. Plasma
      concentrations of these compounds correlated with the degree of inhibition. These
      data support the participation of the endothelin system in the rat model of
      balloon angioplasty and suggest that selective ECEi may be effective.

PMID- 12056553
TI  - Simultaneous changes in intracellular calcium and tension induced by endothelin-1
      and sarafotoxin S6c in guinea pig isolated gallbladder: influence of
      indomethacin.
AB  - The relationships between changes in intracellular Ca2+ and smooth muscle tension
      triggered by endothelin-1 and the selective endothelin ETB receptor agonist
      sarafotoxin S6c, as well as their susceptibility to modification by the
      nonselective cyclooxygenase blocker indomethacin, were assessed in guinea pig
      isolated gallbladder strips. Cumulative additions of either agonist (1, 10, and
      100 nM) induced simultaneous graded, strongly correlated, slowly developing, and
      sustained changes in tension and intracellular Ca+2 (Fura-2 technique).
      Sarafotoxin S6c was more effective than endothelin-1 in raising intracellular
      Ca2+ at 1 or 10 nM, but their abilities to cause contractions were similar at all
      concentrations. Indomethacin (5.6 microM) markedly inhibited the changes in both
      intracellular Ca2+ and tension caused by all concentrations of sarafotoxin S6c
      (in response to 100 nM, increases in Ca2+ fluorescence intensity and tension were
      inhib ited from 7.7 +/- 0.7 to 4.0 +/- 0.4% and from 460 +/- 100 to 160 +/- 40
      mg, respectively) but only reduced the contraction triggered by 100 nM endothelin
      1 (from 560 +/- 100 to 230 +/- 70 mg). Endothelin-1 caused greater prostacyclin
      release from gallbladder than sarafotoxin S6c (at 100 nM, 6-keto-PGF1alpha levels
      in the medium rose 4.8- and 2.8-fold, respectively; P < 0.05) and slightly
      increased thromboxane A2 release (1.6-fold; P < 0.05). Thus, gallbladder
      contractions triggered by combined ETA/ETB or selective ETB receptor stimulation
      (with endothelin-1 or sarafotoxin S6c, respectively) are strongly correlated with
      increases in intracellular Ca2+ but differentially affected by indomethacin. It
      remains to be assessed if this difference is because endothelin-1 triggers
      greater prostacyclin release than sarafotoxin S6c and (or) is due to the coupling
      of ETA and ETB receptors to distinct patterns of generation of cyclooxygenase
      derived eicosanoids.

PMID- 12056554
TI  - Dipeptide sulfonamides as endothelin ETA/ETB receptor antagonists.
AB  - Endothelin-1 (ET-1) is a potent mitogen and modulator of vascular tone. It is
      synthesized and released from endothelial cells and acts upon two receptor
      subtypes designated as ETA and ETB. In this study, a series of potent dipeptide
      sulfonamide dual-endothelin ETA/ETB receptor antagonists were prepared to
      investigate their potential benefit in vascular diseases. CGS 31398 inhibited
      [125I]ET-1 binding to human ETA and ETB receptors expressed in Chinese hamster
      ovary (CHO) cells (ETA/CHO, ETB/CHO) with respective IC50 values of 0.26 and 0.12
      nM. However, in anesthetized rats, this compound markedly potentiated ET-1
      induced renal vascular resistance, a response normally observed with selective
      ETB receptor antagonists. To determine whether species differences account for
      these results, a direct comparison was made between binding to rat and rabbit
      aortic membranes versus functional antagonism in isolated rat aortic rings. It
      was found that CGS 31398 had potent affinity for the ETA receptor in rat and
      rabbit aorta with IC50 values of 0.87 and 0.79 nM, respectively. Inhibition of ET
      1-induced contractions of rat aorta by the compound was considerably weaker than
      expected (pKB = 6.4), while that of sarafotoxin S6c induced contraction of dog
      saphenous vein (100% inhibition at 100 nM) was consistent with corresponding
      binding data. These results suggest that although CGS 31398 is a potent dual
      inhibitor of ETA/ETB receptor binding, it surprisingly displays potent ETB and
      weak ETA receptor antagonism in functional assays.

PMID- 12056555
TI  - Upregulation of endothelin-1 binding in tissues of salt-loaded stroke-prone
      spontaneously hypertensive rats.
AB  - Upon maintained on a 1% NaCl drinking solution beginning at 7 weeks of age, the
      stroke-prone spontaneously hypertensive rat (SHRsp) developed severe hypertension
      and stroke; most died by 16 weeks. The mechanism by which these diseases evolve
      remains unclear. Endothelin-1 (ET-1) is a potent, peptidic vasoconstrictor and is
      implicated in the pathogenesis of various cardiovascular, renal, and central
      nervous system diseases. The purpose of the present study was to compare the
      binding of [125I]ET-1 to the brain, heart, kidney, liver, and spleen membrane
      preparations of 16-week-old SHRsp and age-matched normotensive Wistar-Kyoto rats
      (WKY). The KD values for [125I]ET-1 binding to the corresponding tissues of the
      two strains were not significantly different, except in the brain (SHRsp: 17 +/-
      1 pM; WKY: 24 +/- 1 pM). In contrast, the Bmax values measured in the brain,
      heart, kidney, and liver of SHRsp were 1.5- to 2.1-fold greater than those of
      their WKY counterparts. Competition of [125I]ET-1 binding to the membrane
      preparations by the specific ETA receptor antagonist BQ-123 or the specific ETB
      receptor agonist sarafotoxin S6c revealed a similar proportion of ETA and ETB
      receptor subtypes in the corresponding tissues of the two rat strains. These
      results indicate that ET-1 binding is upregulated in SHRsp and suggest that ET-1
      may play a pathophysiological role in this animal model of genetic hypertension.

PMID- 12056556
TI  - Structural similarity between the bone marrow extracellular matrix protein and
      neurokinin 1 could be the limiting factor in the hematopoietic effects of
      substance P.
AB  - In the adult bone marrow (BM), immune cells are replenished through the process
      of definitive hematopoiesis, which is regulated by a complex process of cellular
      and humoral interactions. The latter include substance P (SP), a neurotransmitter
      that is produced by neural and nonneural cells. Neurokinin-1 (NK-1), the high
      affinity SP receptor, shares structural similarity with fibronectin, a component
      of the BM extracellular matrix proteins. This study examines how such similarity
      could alter the effects of SP on the proliferation of the immature BM
      progenitors. In vitro studies show that 1 ng fibronectin/mL enhanced the
      stimulatory effect of SP on the proliferation of primitive BM progenitors. This
      finding was studied by computational studies: proteomics and three-dimensional
      molecular modeling. Use of surface-enhanced laser desorption/ionization
      ProteinChip technology showed that despite the induction of neutral
      endopeptidase, exogenous fibronectin hindered the degradation of SP to SP(1-4).
      These findings support a protective role for fibronectin in the digestion of SP.
      Since SP(1-4) is a negative regulator of hematopoiesis, this report indicates
      that the structural similarity between fibronectin and NK-1 could be important
      for maintaining hematopoietic stimulation. These studies could be extrapolated to
      hematological disorders that are associated with SP-fibronectin complexes.

PMID- 12056557
TI  - Biochemical and pharmacological activities of SSR 146977, a new potent nonpeptide
      tachykinin NK3 receptor antagonist.
AB  - SSR 146977 is a potent and selective antagonist of the tachykinin NK3 receptor.
      In Chinese hamster ovary cells expressing the human tachykinin NK3 receptor, SSR
      146977 inhibited the binding of radioactive neurokinin B to NK3 receptors (Ki =
      0.26 nM), senktide (10 nM) induced inositol monophosphate formation (IC50 = 7.8
      13 nM), and intracellular calcium mobilization (IC50 = 10 nM). It antagonized
      [MePhe7]neurokinin B induced contractions of guinea pig ileum (pA2 = 9.07).
      Senktide (30 nM) induced firing rate increase of noradrenergic neurons in the
      guinea pig locus coeruleus and dopaminergic neurons in the guinea pig substantia
      nigra was also blocked by SSR 146977 (50 and 100 nM, respectively). In vivo, in
      the respiratory system, SSR 146977 inhibited bronchial hyperresponsiveness to
      acetylcholine, bronchial microvascular permeability hypersensitivity to histamine
      (doses of 0.1-1 mg/kg i.p.), and cough (doses of 0.03-1 mg/kg i.p.) provoked by
      citric acid in guinea pigs. In the central nervous system, SSR 146977 inhibited
      turning behaviour (ID50 = 0.2 mg/kg i.p. and 0.4 mg/kg p.o.) and prevented the
      decrease of locomotor activity (10 and 30 mg/kg i.p) mediated by the stimulation
      of NK3 receptors in gerbils. In guinea pigs, SSR 146977 antagonized senktide
      induced acetylcholine release in the hippocampus (0.3 and 1 mg/kg i.p) and
      norepinephrine release in the prefrontal cortex (0.3 mg/kg i.p.). It also
      prevented haloperidol-induced increase of the number of spontaneously active
      dopamine A10 neurons (1 and 3 mg/kg i.p.).

PMID- 12056558
TI  - New insights into the antidepressant actions of substance P (NK1 receptor)
      antagonists.
AB  - Considerable progress has been made in understanding the neural circuits involved
      the antidepressant and anxiolytic efficacy of substance P (NK, receptor)
      antagonists (SPAs). Progress has been hampered by species differences in the
      pharmacology of the NK1 receptor, and the availability of NK1R-/- mice has been a
      particularly useful resource in overcoming this difficulty. Using
      neuroanatomical, behavioural, and electrophysiological techniques, studies have
      now established that pharmacological blockade or deletion of the NK1 receptor
      produces an antidepressant and anxiolytic-like profile in a range of behavioural
      assays that is distinct from that of established drugs. There is evidence from
      focal injection studies that some of these effects may be mediated directly by
      blockade of NK, receptors in the amygdala and its projections to the
      hypothalamus, periaqueductal gray, and reticulopontine nucleus. Substance P and
      NK1 receptors are also intimately associated with ascending 5-HT and
      norepinephrine projections to the forebrain, and alterations in the function of
      these systems are also likely to be related to the antidepressant efficacy of
      SPAs. Unlike some established drugs, SPAs are generally well tolerated and do not
      induce sedation or motor impairment in preclinical species. These findings are
      consistent with a novel antidepressant mechanism of action of SPAs.

PMID- 12056559
TI  - Regulation of nociceptive neurons by nerve growth factor and glial cell line
      derived neurotrophic factor.
AB  - Nociceptive dorsal root ganglion (DRG) cells can be divided into three main
      populations, namely (1) small diameter non-peptide-expressing cells, (2) small
      diameter peptide-expressing (calcitonin gene related peptide (CGRP), substance P)
      cells, and (3) medium-diameter peptide-expressing (CGRP) cells. The properties of
      these cell populations will be reviewed, with a special emphasis on the
      expression of the vanilloid (capsaicin) receptor VR1 and its regulation by growth
      factors. Cells in populations 1 and 2 express VR1, a nonselective channel that
      transduces certain nociceptive stimuli and that is crucial to the functioning of
      polymodal nociceptors. Cells in population 1 can be regulated by glial cell line
      derived neurotrophic factor (GDNF) and those in populations 2 and 3 by nerve
      growth factor (NGF). In vivo, DRG cells express a range of levels of VR1
      expression and VR1 is downregulated after axotomy. However, treatment with NGF or
      GDNF can prevent this downregulation. In vitro, DRG cells also show a range of
      VR1 expression levels that is NGF and (or) GDNF dependent. Functional studies
      indicate that freshly dissociated cells also show differences in sensitivity to
      capsaicin. The significance of this is not known but may indicate a difference in
      the physiological role of cells in populations 1 and 2.

PMID- 12056560
TI  - Ion trap mass spectrometry: a personal perspective.
AB  - This paper is a personal perspective of the commercial development of the three
      dimensional quadrupole ion trap mass spectrometer. Early ion trap invention and
      development which dates back to 1953, is described. The development of the ion
      trap is traced through three ages with the last age being where commercial
      development takes place. Key technical breakthroughs in ion trap technology and
      commercialization are presented and described up to the present time.

PMID- 12056561
TI  - Matrix methods for the calculation of stability diagrams in quadrupole mass
      spectrometry.
AB  - The theory of the computer calculation of the stability of ion motion in periodic
      quadrupole fields is considered. A matrix approach for the numerical solution of
      the Hill equation and examples of calculations of stability diagrams are
      described. The advantage of this method is that it can be used for any periodic
      waveform. The stability diagrams with periodic rectangular waveform voltages are
      calculated with this approach. Calculations of the conventional stability diagram
      of the 3-D ion trap and the first six regions of stability of a mass filter with
      this method are presented. The stability of the ion motion for the case of a
      trapping voltage with two or more frequencies is also discussed. It is shown that
      quadrupole excitation with the rational angular frequency omega = Nomega/P (where
      N, P are integers and omega is the angular frequency of the trapping field) leads
      to splitting of the stability diagram along iso-beta lines. Each stable region of
      the unperturbed diagram splits into P stable bands. The widths of the unstable
      resonance lines depend on the amplitude of the auxiliary voltage and the
      frequency. With a low auxiliary frequency splitting of the stability diagram is
      greater near the boundaries of the unperturbed diagram. It is also shown that
      amplitude modulation of the trapping RF voltage by an auxiliary signal is
      equivalent to quadrupole excitation with three frequencies. The effect of
      modulation by a rational frequency is similar to the case of quadrupole
      excitation, although splitting of the stability diagram differs to some extent.
      The methods and results of these calculations will be useful for studies of
      higher stability regions, resonant excitation, and non-sinusoidal trapping
      voltages.

PMID- 12056562
TI  - "Dueling" ESI: instrumentation to study ion/ion reactions of electrospray
      generated cations and anions.
AB  - Novel instrumentation has been developed which allows for the sequential
      injection and subsequent reaction of oppositely-charged ions generated via
      electrospray ionization (ESI) in a quadrupole ion trap mass spectrometer. The
      instrument uses a DC turning quadrupole to sequentially direct the two ion
      polarities into the ion trap from ESI sources which are situated 90 degrees from
      the axial (z) dimension of the trap, and 180 degrees from one another. This
      arrangement significantly expands the range of ionic reactants amenable to study
      over previously-used instrumentation. For example, ion/ion reactions of multiply
      charged positive ions with multiply-charged negative ions can be studied. Also,
      reactions of multiply-charged ions with singly-charged ions of opposite polarity
      that could not be generated by previously used ionization methods, or that could
      not be efficiently injected through the ion trap ring electrode, can be studied
      with the new instrument. This capability allows, for example, the charge state
      manipulation of negatively-charged precursor and product ions derived from
      proteins and oligonucleotides via proton transfer reactions with singly-charged
      cations generated by ESI.

PMID- 12056563
TI  - Correlations of chemical mass shifts of para-substituted acetophenones and
      benzophenones with Brown's sigma constants.
AB  - Relationships between chemical mass shifts and physiochemical properties of ions
      are sought by examining substituted acetophenones, benzophenones, and pyridines
      in a modified ion trap mass spectrometer. Systematic changes in chemical mass
      shift occur with changes in substituent in the acetophenones and the
      benzophenones. Brown's sigma+ constant, which is a measure of electronic effects
      of substituents in reactions that involve positive charge development, is shown
      to correlate linearly with chemical mass shifts in para-substituted acetophenones
      and benzophenones. Brown's sigma+ constant also correlates with the ease of
      dissociation of the ions via a correlation with ionization energy. It is
      suggested that ease of dissociation is the underlying factor in determining
      chemical mass shifts. The experimental results also suggest that dissociative
      collisions between ions and buffer gas make a much greater contribution to
      chemical mass shifts than do elastic collisions.

PMID- 12056564
TI  - Characterization of erythromycin analogs by collisional activated dissociation
      and infrared multiphoton dissociation in a quadrupole ion trap.
AB  - The effectiveness of two activation techniques, collision activated dissociation
      (CAD) and infrared multiphoton dissociation (IRMPD), is compared for structural
      characterization of protonated and lithium-cationized macrolides and a series of
      synthetic precursors in a quadrupole ion trap (QIT). Generally, cleavage of the
      glycosidic linkages attaching the sugars to the macrolide ring and water losses
      constitute the major fragmentation pathways for most of the protonated compounds.
      In the IRMPD spectra, a diagnostic fragment ion assigned as the desosamine ion is
      a dominant ion that is not observed in the CAD spectra because of the higher m/z
      limit of the storage range required during collisional activation. Activation of
      the lithium-cationized species results in new diagnostic fragmentation pathways
      that are particularly useful for confirming the identities of the protecting
      groups in the synthetic precursors. Multi-step IRMPD allows mapping of the
      fragmentation genealogies in greater detail and supports the proposed structures
      of the fragment ions.

PMID- 12056565
TI  - Collision-induced signal enhancement (CISE): the use of boundary activation to
      effect non-resonant CISE.
AB  - An alternative to resonant excitation collision-induced signal enhancement (CISE)
      is presented. This alternative utilizes boundary activation instead of resonant
      excitation to effect CISE and is called boundary activated collision induced
      signal enhancement (BA-CISE). There are three ways to effect BA-CISE to enhance
      the signal for an MS(n+1) experiment. Each technique utilizes the beta(z) = 0
      boundary, which ions encounter from high to low mass/charge ratio. BA-CISE is
      shown to produce an almost 900% increase in the C2 ion of [maltohexaose + Li]+.
      The use of a heavy collision gas in addition to the helium bath gas generally
      produced a signal enhancement inferior to the same experiment without the heavy
      gas.

PMID- 12056566
TI  - A two-dimensional quadrupole ion trap mass spectrometer.
AB  - The use of a linear or two-dimensional (2-D) quadrupole ion trap as a high
      performance mass spectrometer is demonstrated. Mass analysis is performed by
      ejecting ions out a slot in one of the rods using the mass selective instability
      mode of operation. Resonance ejection and excitation are utilized to enhance mass
      analysis and to allow isolation and activation of ions for MS(n) capability.
      Improved trapping efficiency and increased ion capacity are observed relative to
      a three-dimensional (3-D) ion trap with similar mass range. Mass resolution
      comparable to 3-D traps is readily achieved, including high resolution at slower
      scan rates, although adequate mechanical tolerance of the trap structure is a
      requirement. Additional advantages of 2-D over 3-D ion traps are also discussed
      and demonstrated.

PMID- 12056567
TI  - Branching pattern and sequence analysis of underivatized oligosaccharides by
      combined MS/MS of singly and doubly charged molecular ions in negative-ion
      electrospray mass spectrometry.
AB  - We previously reported that sequence and partial linkage information, including
      chain and blood-group types, of reducing oligosaccharides can be obtained from
      negative-ion electrospray CID MS/MS on a quadrupole-orthogonal time-of-flight
      instrument with high sensitivity and without derivatization (Chai, W.; Piskarev,
      V.; Lawson, A. M. Anal. Chem. 2001, 73, 651-657). In contrast to oligonucleotides
      and peptides, oligosaccharides can form branched structures that result in a
      greater degree of structural complexity. In the present work we apply negative
      ion electrospray CID MS/MS to core-branching pattern analysis using nine 3,6
      branched and variously fucosylated oligosaccharides based on hexasaccharide
      backbones LNH/LNnH as examples. The important features of the method are the
      combined use of CID MS/MS of singly and doubly charged molecular ions of
      underivatized oligosaccharides to deduce the branching pattern and to assign the
      structural details of each of the 3- and 6-branches. These spectra give
      complimentary structural information. In the spectra of [M - H]-, fragment ions
      from the 6-linked branch are dominant and those from the 3-linked branch are
      absent, while fragment ions from both branches occur in the spectra of [M - 2H]2
      . This allows the distinction of fragment ions derived from either the 3- or 6
      branches. In addition, a unique D2beta-3 ion, arising from double D-type cleavage
      at the 3-linked glycosidic bond of the branched Gal core residue, provides direct
      evidence of the branching pattern with sequence and partial linkage information
      being derived from C- and A-type fragmentations, respectively.

PMID- 12056568
TI  - Structural studies on ceramides as lithiated adducts by low energy collisional
      activated dissociation tandem mass spectrometry with electrospray ionization.
AB  - We applied electrospray ionization (ESI) tandem quadrupole mass spectrometry to
      establish the fragmentation pathways of ceramides under low energy collisional
      activated dissociation (CAD) by studying more than thirty compounds in nine
      subclasses. The product-ion spectra of the [M + Li]+ ions of ceramides contain
      abundant fragment ions that identify the fatty acyl substituent and the long
      chain base (LCB) of the molecules, and thus, the structure of ceramides can be
      easily determined. Fragment ions specific to each ceramide subclasses are also
      observed. These feature ions permit differentiation among different ceramide
      subclasses. The ion series arising from the classical C-C bond cleavages that
      were reported in the fast-atom bombardment (FAB)-high energy tandem mass
      spectrometry is not observable; however, the product-ion spectra contain multiple
      fragment ions informative for structural characterization and isomer
      identification. We also investigated the tandem mass spectra of the fragment ions
      generated by in-source CAD (pseudo-MS3) and of the deuterium-labeling molecular
      species obtained by H/D exchange to support the ion structure assignments and the
      proposed fragmentation pathways that lead to the ion formation.

PMID- 12056569
TI  - Pulsed fluorescence measurements of trapped molecular ions with zero background
      detection.
AB  - Sensitive methods have been developed to measure laser-induced fluorescence from
      trapped ions by reducing the detection of background scattering to zero levels
      during the laser excitation pulse. The laser beam diameter has been reduced to
      approximately 150 microm to eliminate scattering on trap apertures and the
      resulting laser-ion interaction is limited to a volume of approximately 10(-5) cm
      which is approximately 0.03-0.15 of the total ion cloud volume depending on
      experimental conditions. The detection optics collected fluorescence only from
      within the solid angle defined by laser-ion interaction volume. Rhodamine 640 and
      Alexa Fluor 350 ions, commonly used as fluorescence resonance energy transfer
      (FRET) fluorophores, were generated in the gas phase by using electrospray
      ionization and injected into a radiofrequency Paul trap where they were stored
      and exposed to Nd:YAG laser pulses at 532 and 355 nm for times up to 10 m.
      Fluorescence emitted by these ions was investigated for several trap q(z) values
      and ion cloud temperatures. Analysis of photon statistics indicated an average of
      approximately 10 photons were incident on the PMT detector per 15 ns pulse for
      approximately 10(3) trapped ions in the interaction volume. Fluorescence
      measurements displayed a dependence on trapped ion number which were consistent
      with calculations of the space charge limited ion density. To investigate the
      quantitative capability of these fluorescence techniques, the laser-induced
      fragmentation of trapped Alexa Fluor 350 ions was measured and compared with a
      rate equation model of the dynamics. Decay of the fluorescence signal as well as
      the parent ion number compared closely with quantitative predictions of the
      photofragmentation model.

PMID- 12056570
TI  - Electrospray low energy CID and MALDI PSD fragmentations of protonated
      sulfinamide cross-linked peptides.
AB  - Murine S100A8 (A8) is a major cytoplasmic neutrophil protein and is converted to
      novel oxidation products containing Cys-epsilon amino-Lys sulfinamide cross-links
      and Met-sulfoxide by the neutrophil oxidant HOCl. Seven products were separated
      using RP-HPLC, with electrospray ionization mass spectrometry (ESI-MS) masses
      after deconvolution of 10,354, 10,388, +/- 1, and 20,707, +/- 3 Da, and all were
      resistant to reduction by dithiothreitol. The major products with masses of
      10,354 Da contained Cys41-Lys34/35 intramolecular cross-links. Additional
      isomeric products with identical masses (10,354 Da) were isolated and peptide
      mapping and ESI/MS indicated that Cys41 forms covalent sulfinamide cross-links
      with either Lys6, Lys76, Lys83, or Lys87 present in A8. Electrospray low energy
      collisionally induced (CID) spectra of multiply-charged AspN digest peptides with
      sulfinamide cross-links contained characteristic fragmentations that corresponded
      to simple cleavage of the nitrogen-sulfur bond with charge retention on either of
      the fragment ions, allowing conformation of cross-linked peptides. Matrix
      assisted laser desorption/ionization time-of-flight (MALDI-TOF) post source decay
      spectra of [M + H] + ions of the same sulfinamide-containing cross-linked
      peptides fragment similarly, but additional facile fragmentation reactions
      corresponding to formation of a protonated peptide containing de-hydroalanine
      were attributed to cleavage of the carbon-sulfur bond. In addition, lose of
      methanesulfenic acid from Met-sulfoxide was observed. A sulfinamide-containing
      adduct was isolated after incubation of the A8/HOCl reaction mixture with Lys or
      alpha N-acetyl Lys with masses of 10,500 or 10,542 Da. ESI/MS/MS and MALDI/post
      decay source (PSD) analysis of A8(32)-(57)-sulfinamide showed the same
      characteristic fragmentations as those in the sulfinamide cross-linked peptides,
      confirming the Cys41-Lys sulfinamide cross-link and suggesting that peptide
      peptide sulfinamides may all fragment similarly, allowing ready identification of
      these cross-links in proteins from more complex biological materials.

PMID- 12056571
TI  - Dissociation of different conformations of ubiquitin ions.
AB  - The fragmentation pathways of different conformations of three charge states of
      ubiquitin ions are examined using ion mobility/collisional activation/time-of
      flight techniques. Mass spectra for fragments for different conformers of a
      single charge state appear to be identical (within the experimental
      reproducibility). These results are consistent with a mechanism in which
      different conformers of each charge state rearrange to similar dissociation
      transition states prior to fragment formation.

PMID- 12056572
TI  - Characterization of lipooligosaccharides from Haemophilus ducreyi containing
      polylactosamine repeats.
AB  - Haemophilus ducreyi, a gram-negative human mucosal pathogen, is one of the
      principal causes of genital ulcer disease. The lipooligosaccharides (LOS) of
      these bacteria are considered to be a major virulence factor and have been
      implicated in the adherence and invasion of H. ducreyi to several human cell
      types. An isogenic heptosyltransferase-III knockout strain (waaQ) was recently
      constructed from H. ducreyi 35000 wild-type strain and immunochemical and
      molecular weight data of the isolated LOS suggested the presence of poly-N
      acetyllactosamine (LacNAc) (Filiatrault et al., Infect. Immun. 2000, 68, 3352
      3361). In this present study, the structures of these novel LOS-glycoforms were
      characterized by matrix-assisted laser desorption/ionization (MALDI) and
      electrospray ionization (ESI) mass spectrometry in combination with
      exoglycosidase digestion. Detailed structural information was obtained for the
      oligosaccharide (OS) portions of these LOS showing between one to five linear
      LacNAc repeats on the non-reducing terminus of the main oligosaccharide branch.
      When grown on solid media, the organism produced LacNAc repeats that were further
      modified by the addition of sialic acid. Enzymatic digestion with beta
      galactosidase, beta-N-acetylhexosaminidase, and neuraminidase type VI-A yielded
      truncated glycoforms consistent with a polyLacNAc structure capped at various end
      points with sialic acid. ESI-MS/MS mass spectrometry on a quadrupole time-of
      flight instrument was particularly effective in obtaining detailed structural
      information on the least abundant, high-mass glycoforms. Although LOS containing
      terminal di-LacNAc have been reported, this is the first time to our knowledge
      that a linear polyLacNAc structure has been characterized in bacteria.

PMID- 12056573
TI  - Scanning microprobe matrix-assisted laser desorption ionization (SMALDI) mass
      spectrometry: instrumentation for sub-micrometer resolved LDI and MALDI surface
      analysis.
AB  - A new instrument and method is described for laterally resolved mass
      spectrometric surface analysis. Fields of application are in both the life
      sciences and the material sciences. The instrument provides for imaging of the
      distribution of selected sample components from natural and artificial surfaces.
      Samples are either analyzed by laser desorption ionization (LDI) time-of-flight
      mass spectrometry or, after preparation with a suitable matrix, by matrix
      assisted laser desorption ionization (MALDI) mass spectrometry. Areas of 100 x
      100 microm are scanned with minimal increments of 0.25 microm, and between 10,000
      and 160,000 mass spectra are acquired per image within 3 to 50 min (scan rate up
      to 50 pixels per s). The effective lateral resolution is in the range of 0.6 to
      1.5 microm depending on sample properties, preparation methods and laser
      wavelength. Optical investigation of the same sample area by UV confocal scanning
      laser microscopy was found to be very attractive in combination with scanning
      MALDI mass analysis because pixel-identical images can be created with both
      techniques providing for a strong increase in analytical information. This
      article describes the method and instrumentation, including first applicational
      examples in elemental analysis, imaging of pine tree roots, and investigation of
      MALDI sample morphology in biomolecular analysis.

PMID- 12056574
TI  - Laser hair removal.
AB  - The presence of unwanted hair continues to plague many individuals for whom
      traditional methods of hair removal remain unsatisfactory. Laser and flashlamp
      technology now offers the potential for rapid, safe, and effective treatment of
      unwanted hair. An ever-increasing number of published studies have confirmed the
      long-term efficacy of laser and flashlamp treatment. For the most part, however,
      the benefits of this technology have been limited to individuals with dark hair
      and relatively fair skin. The remaining challenge is to develop the means to
      eliminate light-colored hair as well as the capability to safely treat
      individuals with darker skin. The rapid pace of technological advancement as well
      as continued studies of hair follicle biology promise to improve this field over
      the years to come.

PMID- 12056575
TI  - P300 amplitude over temporal regions in schizophrenia.
AB  - To examine the left temporal scalp area reductions of P300 amplitude, event
      related potentials (ERPs) during a standard oddball task were recorded in 57
      schizophrenic patients and 33 normal controls. The P300 amplitude at T3 was not
      significantly smaller than that at T4 in schizophrenic patients. In the ANOVA
      analysis of the P300 peak amplitude and PCA factor scores, significant lateral
      topographical differences in P300 were not present between patients and controls.
      However, in schizophrenia, patients in the low T3 P300 group were older and
      consuming higher doses of antipsychotic medicine than those in the high T3 P300
      group, and they had relatively low P300 amplitudes and significantly delayed P300
      latency, compared with those in the high T3 P300 group. These findings suggested
      that although the reduction in the left temporal P300 amplitude did not
      necessarily exist in schizophrenic patients, it may be associated with the
      severity of the disease process and/or impairment of cognitive function.

PMID- 12056576
TI  - Classifying psychotic disorders: issues regarding categorial vs. dimensional
      approaches and time frame to assess symptoms.
AB  - The study's aims were to empirically derive classes of disorders and dimensional
      syndromes within psychotic disorders on the basis of the three time frames of
      symptom assessment and to comparatively examine their external validity. The
      level of concordance among classes and among dimensions across the time frames
      was generally low. The external correlates of psychopathological syndromes
      differed as a function of both type of assessment and the dimensional or
      categorical approach used. The dimensional approach was more effective than the
      categorical approach in predicting a set of clinical variables, irrespective of
      the time frame used to assess the symptoms. It is concluded that classification
      of psychotic disorders is highly dependent upon the time frame considered to
      assess symptoms and that dimensional classifications do have higher predictive
      power than categorical ones.

PMID- 12056577
TI  - Is patient satisfaction a unidimensional construct? Factor analysis of the Munich
      Patient Satisfaction Scale (MPSS-24).
AB  - Although patients' satisfaction with treatment has gained much attention,
      conceptual and methodological issues are not sufficiently investigated.
      Consequently, well-validated satisfaction scales are rare. In order to respond to
      methodological requirements being associated with the measurement of patient
      satisfaction, the Munich Patient Satisfaction Scale (MPSS-24) was developed for
      psychiatric in-patients. The scale was validated on the basis of three
      independent samples (n=85, n= 161, n=91), and the effects of moderating variables
      were controlled. In several steps of item selection the initial pool of 133 items
      was reduced to 24 items, which were subjected to factor analysis. The MPSS-24
      demonstrates one major principal component with two minor factors which indicates
      that doctor-patient communication is the essential source for patient
      satisfaction. The instrument is of high internal consistency and reliability, and
      convergent validity is satisfactory.

PMID- 12056578
TI  - Subjective experiences in schizophrenia and bipolar disorders.
AB  - Studies comparing 'subjective experiences' in schizophrenic and affective
      disorders have reached inconclusive results. We investigated the pattern of
      'subjective perceived cognitive disturbances' in a group of 55 schizophrenic
      patients and 39 bipolar patients hospitalized for an index psychotic episode. The
      assessment of the subjective experiences was made using the Frankfurter
      Beschwerde-Fragebogen (FBF). Comparing the two groups on the four FBF factors,
      schizophrenic patients showed significantly higher scores in the areas of
      'central cognitive disturbances', 'perception and motility' other than a
      significantly higher FBF total score. Our results suggest that cognitive,
      perception and motility disturbances are the most characteristic subjective
      experiences of schizophrenic patients in comparison with bipolar patients. This
      finding need to be further explored in light of the issue of cognitive
      dysfunction in schizophrenia.

PMID- 12056579
TI  - The occurrence of suicide in severe depression related to the months of the year
      and the days of the week.
AB  - The purpose of the present study was to investigate the distribution of suicide
      during the months of the year and the days of the week in severe depression. A
      total of 1206 in-patients rated at discharge from the Department of Psychiatry,
      Lund, Sweden, on a multiaxial diagnostic schedule received the diagnosis severe
      depression/melancholia between 1956 to 1969. When followed up to 1998, a total of
      114 depressed patients had taken their own life. Out of these, 98 patients
      appeared to have a primary depression. The monthly distribution of suicides
      showed a significant peak in October/November for men (41 % of all male
      suicides). No correlation with the onset of depression could be detected.
      Furthermore, there was a preponderance of suicide on Sundays for both sexes (31 %
      of all suicides).

PMID- 12056580
TI  - Neurocognitive performance in first-episode and chronic schizophrenic patients.
AB  - Previous research on neuropsychological disturbances in first-episode and chronic
      schizophrenic patients has provided mixed results which can be partially
      attributed to methodological inconsistencies. For the present study, 70
      schizophrenic patients (40 with chronic and 30 with first-episode schizophrenia)
      were compared to 30 healthy controls on a large battery of neuropsychological
      tests. Special attention was paid to potential confounds such as differences in
      psychopathology, age and educational level between the schizophrenic sub-samples.
      Healthy controls performed better than both first-episode and chronic patients in
      almost all cognitive domains (P < 0.01), while the patient samples did not differ
      in any of the tasks. Results were confirmed in a second series of analyses in
      which patient subgroups were equated for sociodemographic background variables.
      The present results confirm recent data collected in longitudinal studies, thus,
      lending further support for a neurodevelopmental model of schizophrenia. It is
      suggested that neuropsychological disturbances occur early in schizophrenia and
      do not worsen in the course beyond age-related decrement. Possible reasons why
      previous research has produced contradictory findings are discussed.

PMID- 12056582
TI  - Neuro-Behcet's disease involving the pons with initial onset of affective
      symptoms.
AB  - We report a case with Behcet's disease with initial onset of affective symptoms.
      This disease most commonly affects the brain stem in the nervous system, but a
      large lesion is very rare in the pons; initial onset of affective symptoms has
      not yet been reported in literature. This case was treated successfully with
      corticosteroids. Total clinical improvement was observed and the lesion was
      reduced in size within nine months (1.5 x 1.3 cm to 0.2 x 0.4 cm).

PMID- 12056581
TI  - Biogenic amine turnover and serum cholesterol in suicide attempt.
AB  - The investigation of biological correlates of suicidal behavior is important in
      searching for possible changes in neuronal systems activity related to that
      behavior, so that pharmacological interventions may be proposed, especially in
      high-risk subjects. In a sample of 111 subjects admitted in a general hospital
      after suicide attempt, we studied the turnover of neurotransmitters by measuring
      the urinary output of the main metabolites of serotonin, dopamine and
      noradrenaline (5-HIAA, HVA, MHPG respectively), as well as serum cholesterol, and
      compared them to those of a group of 62 healthy controls. Venous blood samples
      and urine samples were collected within 24 hours of admission. Psychiatric
      diagnosis was made according to DSM-IIIR criteria and assessment of suicide
      intent with Beck's Suicidal Intent Scale (SIS). Fifty-four (54) subjects received
      the diagnosis of adjustment disorder, 25 of depression, 16 of schizophrenia and
      16 of personality disorder. Fourteen subjects (14) had employed a violent mode of
      attempt. Urinary MHPG was found significantly higher in all diagnostic groups
      compared to controls. No difference was found concerning the excretion of HVA and
      5-HIAA. Serum total cholesterol was found significantly lower both in violent and
      non-violent attempters compared to controls after correcting for age. No
      difference in serum cholesterol or MHPG was found between violent and non-violent
      attempts. Serum cholesterol and MHPG correlated negatively, while the
      correlations between cholesterol and 5-HIAA or HVA were not significant. Our
      results confirm previous reports of lower serum cholesterol in attempted suicide.
      They are also indicative of an increased noradrenaline turnover in subjects who
      attempt suicide, at least within 24 hours after the attempt. Whether this
      activation precedes or follows the attempt because of the specific stress, can
      not be answered at present.

PMID- 12056583
TI  - Total serum cholesterol level, violent criminal offences, suicidal behavior,
      mortality and the appearance of conduct disorder in Finnish male criminal
      offenders with antisocial personality disorder.
AB  - Associations between low total serum cholesterol (TC) levels and antisocial
      personality disorder (ASPD), violent and suicidal behavior have been found. We
      investigated the associations between TC levels, violent and suicidal behavior,
      age of onset of the conduct disorder (CD) and the age of death among 250 Finnish
      male criminal offenders with ASPD. The CD had begun before the age of 10 two
      times more often in non-violent criminal offenders who had lower than median TC
      levels. The violent criminal offenders having lower than median TC levels were
      seven times more likely to die before the median age of death in the study
      material. The violent offenders having lower than median TC levels were eight
      times more likely to die of unnatural causes. The mean TC level of these male
      offenders with ASPD was lower than that of the general Finnish male population.
      Low TC levels are associated with childhood onset type of the CD, and premature
      and unnatural mortality among male offenders with ASPD. The TC level seems to be
      a peripheral marker with prognostic value among boys with conduct disorder and
      antisocial male offenders.

PMID- 12056584
TI  - Issues concerning the monitoring of statin therapy in hypercholesterolemic
      subjects with high plasma lipoprotein(a) levels.
AB  - Most studies on the topic have shown that statin therapy decreases plasma LDL
      levels but not those of lipoprotein(a) [Lp(a)]. This specificity of action,
      although previously noted, has not been systematically investigated. In the
      current study we approached this problem by monitoring LDL- and Lp(a) cholesterol
      in 80 hypercholesterolemic subjects with high Lp(a) levels, at entry and 8 mon
      after initiation of statin therapy. We found that commonly used direct and
      indirect LDL cholesterol assays gave an LDL cholesterol value that comprised both
      true LDL- and Lp(a) cholesterol. We estimated these two analytes from the values
      of Lp(a) protein determined by ELISA and from knowledge of the Lp(a) chemical
      composition, complemented by data from immunochemical and ultracentrifugal
      analyses. Statin therapy, while not affecting plasma Lp(a) protein levels (21.7+/
      10.4, before, and 22.0+/-10.1 mg/dL, after), caused a decrease in the estimated
      or true LDL cholesterol (P < 0.0001) to values in some cases as low as 10 mg/dL.
      This drop in true LDL was validated by the decrease in the LDL band in the
      ultracentrifugation profiles, and its magnitude was proportional to the degree of
      total cholesterol lowering and to the pretreatment true LDL/Lp(a) cholesterol
      weight ratio. We conclude that true LDL but not Lp(a) cholesterol is affected by
      statin therapy and that this specific response cannot be monitored by current LDL
      cholesterol assays and must, rather, rely on estimates of these two analytes.

PMID- 12056585
TI  - High doses of atorvastatin and simvastatin induce key enzymes involved in VLDL
      production.
AB  - Treatments with high doses of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      reductase inhibitors may induce the expression of sterol regulatory element
      binding protein (SREBP)-target genes, causing different effects from those
      attributed to the reduction of hepatic cholesterol content. The aim of this study
      was to investigate the effects of high doses of statins on the key enzymes
      involved in VLDL production in normolipidemic rats. To examine whether the
      effects caused by statin treatment are a consequence of HMG-CoA reductase
      inhibition, we tested the effect of atorvastatin on these enzymes in mevalonate
      fed rats. Atorvastatin and simvastatin enhanced not only HMG-CoA reductase but
      also the expression of the SREBP-2 gene itself. As a result of the overexpression
      of SREBP-2 caused by the statin treatment, genes regulated basically by SREBP-1,
      as FA synthase and acetyl-coenzyme A carboxylase, were also induced and their
      mRNA levels increased. DAG acyltransferase and microsomal TG transfer protein
      mRNA levels as well as phosphatidate phosphohydrolase activity were increased by
      both statins. Simvastatin raised liver cholesterol content, ACAT mRNA levels, and
      CTP:phosphocholine cytidylyltransferase activity, whereas it reduced liver DAG
      and phospholipid content. Mevalonate feeding reversed all changes induced by the
      atorvastatin treatment. These results show that treatment with high doses of
      statins induces key enzymes controlling rat liver lipid synthesis and VLDL
      assembly, probably as a result of SREBP-2 overexpression. Despite the induction
      of the key enzymes involved in VLDL production, both statins markedly reduced
      plasma TG levels, suggesting that different mechanisms may be involved in the
      hypotriglyceridemic effect of statins at high or low doses.

PMID- 12056586
TI  - Effect of dietary cholesterol oxidation products on the plasma clearance of
      chylomicrons in the rat.
AB  - Oxidized cholesterols in the diet have been shown to exacerbate arterial
      cholesterol deposition and the development of atherosclerosis in animal models.
      Dietary oxidized cholesterols are absorbed through the intestine and incorporated
      into lymph chylomicrons. The aim of this study was to investigate the effect of
      oxidized cholesterols on the metabolism of nascent chylomicrons in vivo. It was
      shown that oxidized cholesterols markedly delay the clearance of chylomicrons
      from plasma compared to rats given TG alone. However, there was no difference in
      the clearance of chylomicrons containing oxidized cholesterols vs. purified
      cholesterol, although the presence of oxysterols did appear to exacerbate the
      removal of these particles from circulation. The impaired clearance of
      chylomicrons containing oxidized cholesterols was not due to impaired lipolysis
      and slower conversion to the remnant form. Moreover, the incorporation of
      oxidized cholesterols did not alter the hepatic or splenic uptake of chylomicrons
      compared to chylomicrons isolated from rats given purified cholesterol or TG
      alone. Collectively, the results of this study suggest that the exacerbated delay
      in clearance of chylomicron remnants enriched with oxysterols may be due to
      impaired uptake by tissues other than the liver and spleen. Apolipoprotein (apo)
      analysis showed that oxysterol incorporation reduced the apoE content and altered
      the apoC phenotype of chylomicrons, which may have an impact on the removal of
      chylomicron remnants from plasma. In conclusion, dietary oxysterols appear to
      have the potential to adversely affect chylomicron metabolism. Therefore, further
      investigations in humans are required to determine whether dietary oxidized
      cholesterols found in cholesterol-rich processed foods delay the clearance of
      postprandial remnants, which may contribute to and exacerbate the development of
      atherosclerosis.

PMID- 12056587
TI  - Changes in the chemical composition of surfactant-like particles secreted by rat
      small intestine in response to different dietary fats.
AB  - Consumption of dietary oil, viz., corn, fish, coconut, or olive, induced the
      secretion of surfactant-like particles (SLP) in rat intestine. These lipoprotein
      particles differ in (i) levels of alkaline phosphatase activity, (ii) lipid
      composition, and (iii) FA composition in response to feeding of different oils.
      The secreted particles had similar buoyancy (1.07-1.08 g/mL) and
      cholesterol/phospholipid molar ratios (0.61-0.72) except that feeding coconut oil
      to rats produced SLP with a low (0.18) cholesterol/phospholipid molar ratio
      compared to control animals. It is concluded from these observations that feeding
      different oils induces the secretion of lipoprotein particles in rat intestine
      with different chemical compositions.

PMID- 12056588
TI  - In vitro effects of fat, FA, and cholesterol on sphingomyelin hydrolysis induced
      by rat intestinal alkaline sphingomyelinase.
AB  - Dietary sphingomyelin (SM) may have regulatory effects on cell proliferation and
      tumorigenesis in the colon. Alkaline sphingomyelinase (SMase) is the major enzyme
      responsible for hydrolysis of SM in the gut. Previously we purified the enzyme
      and showed that the presence of glycerophospholipids inhibited SM hydrolysis
      induced by alkaline SMase in vitro. In the present work, we studied the effects
      of TG, DG, FA, ceramide, and cholesterol on SM hydrolysis catalyzed by purified
      alkaline SMase. The results showed that both TG (triolein and tristearin) and DG
      (1,2-dioleoyl-sn-glycerol and 1,2-distearoyl-rac-glycerol) inhibited the activity
      of alkaline SMase. 1-Monooleoyl-rac-glycerol, 1-monostearoyl-rac-glycerol,
      stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid
      stimulated the activity of alkaline SMase at 0.4-0.8 mM concentrations but
      inhibited the enzyme at higher concentrations. There was no difference between
      the effects induced by saturated and unsaturated FA. A short-chain FA such as
      lauric acid had a stronger stimulatory effect at low concentrations and weaker
      inhibitory effect at high concentrations than long-chain FA. Choosing linoleic
      acid as an example, we found that FA had similar effects on both alkaline SMase
      and neutral SMase. Cholesterol and ceramide when mixed with FA to increase its
      solubility in bile salt micelles inhibited SMase activity. In conclusion,
      glycerides, FA, ceramide, and cholesterol influence SM hydrolysis catalyzed by
      intestinal alkaline SMase. The presence of lipids in the diet may thus influence
      the course of SM digestion in the gut and thereby the exposure of colon to SM
      metabolites.

PMID- 12056589
TI  - Albumin stimulates lysophosphatidic acid acyltransferase activity in T-lymphocyte
      membranes.
AB  - Phosphatidic acid (PtdOH) and lysophosphatidic acid (lysoPtdOH) have been shown
      to enhance T-lymphocyte function. However, the FA preference and influence of
      acyl-CoA binding proteins on lysoPtdOH and PtdOH biosynthesis are not known.
      Therefore, we determined glycerol-3-phosphate acyltransferase (GPAT) and
      lysophosphatidic acid acyltransferase (LAT) activity in rat T-lymphocyte and
      liver membrane preparations in the presence of palmitoyl-CoA and oleoyl-CoA with
      or without BSA. We found two different properties of GPAT and LAT in whole T
      lymphocyte membrane preparations relative to liver. First, T-lymphocyte basal
      GPAT and LAT activities were similar, whereas in liver membranes LAT activity was
      10-fold higher than GPAT. Second, T-lymphocyte LAT, but not GPAT, activity was
      inducible (fivefold) by the addition of albumin in the presence of palmitoyl-CoA
      but not oleoyl-CoA. In contrast, albumin stimulated GPAT, but not LAT, activity
      in liver membranes in the presence of palmitoyl-CoA. These results show, for the
      first time, that T-lymphocyte LAT activity can be increased by the presence of an
      acyl-CoA binding protein, which may indicate a new important control mechanism
      for regulating intracellular lysoPtdOH and PtdOH levels in T-lymphocytes.

PMID- 12056590
TI  - Comparison of the effects of dietary alpha-linolenic, stearidonic, and
      eicosapentaenoic acids on production of inflammatory mediators in mice.
AB  - The effects of dietary stearidonic acid (18:4n-3) on inflammatory mediator
      release in whole blood and splenocytes was investigated in Balb/c mice, and the
      effects were compared with those of two other n-3 PUFA: alpha-linolenic acid
      (18:3n-3) and EPA (20:5n-3). TAG mixtures containing 10% of 18:4n-3, 18:3n-3, or
      20:5n-3 as the respective sole n-3 PUFA were enzymatically synthesized. Diets
      containing synthesized TAG mixtures were fed to Balb/c mice for 3 wk. The release
      of prostaglandin F2 (PGE2) and tumor necrosis factor (TNF) were measured in whole
      blood and splenocytes stimulated with lipopolysaccharide. In whole blood, the
      production of TNF was suppressed by all dietary n-3 PUFA (18:3n-3, 18:4n-3, and
      20:5n-3) as compared with the control diet, which contained TAG prepared from
      safflower oil. PGF2 production was not significantly changed. Differences among
      the n-3 PUFA (18:3n-3, 18:4n-3, and 20:5n-3) were not observed. In splenocytes,
      PGE2 production was suppressed by dietary n-3 PUFA, but TNF production was not.
      GC analysis of plasma and splenocyte FA profiles showed an increase in the levels
      of 20:4n-3, 20:5n-3, and 22:6n-3 in mice fed the diet containing 18:4n-3.

PMID- 12056591
TI  - Peroxisome proliferator-activated receptor alpha,gamma coagonist LY465608
      inhibits macrophage activation and atherosclerosis in apolipoprotein E knockout
      mice.
AB  - The apolipoprotein E (apoE) knockout mouse has provided an approach to the
      investigation of the effect of both cellular and humoral processes on
      atherosclerotic lesion progression. In the present study, pharmacologic
      modulation of both interferon gamma (IFNgamma)-inducible macrophage effector
      functions, and atherosclerotic lesions in the apoE knockout mouse were
      investigated using the peroxisome proliferator-activated receptor (PPAR)
      alpha,gamma coagonist LY465608. LY465608 inhibited, in a concentration-dependent
      manner, IFNgamma induction of both nitric oxide synthesis and the beta 2 integrin
      CD11a in elicited peritoneal macrophages from apoE knockout mice. Similar effects
      were observed ex vivo following 10 d of treating mice with 10 mg/kg of LY465608.
      Treatment of apoE knockout mice for 18 wk with LY465608 resulted in a
      statistically significant 2.5-fold reduction in atherosclerotic lesion area in en
      face aorta preparations. These effects were apparent in the absence of any
      reduction in total serum cholesterol or in lipoprotein distribution. Finally,
      treatment of apoF knockout mice with established atherosclerotic disease resulted
      in a modest but not statistically significant decrease in aortic lesional surface
      area. These results demonstrate the utility of PPAR coagonists in reducing the
      progression of the atherosclerotic lesion.

PMID- 12056592
TI  - Targeted disruption of peroxisomal proliferator-activated receptor beta (delta)
      results in distinct gender differences in mouse brain phospholipid and esterified
      FA levels.
AB  - The peroxisomal proliferator-activated receptor beta (delta) (PPARbeta) is a
      nuclear hormone receptor that is ubiquitously expressed and that regulates the
      transcription of genes involved in lipid metabolism. A homozygous PPARbeta-null
      mouse has been developed in which the ligand-binding domain of the PPARbeta
      receptor is disrupted. Analysis of brains from these animals shows that female
      null mice have 24 and 17% increases in plasmenylethanolamine and
      phosphatidylserine and a 9% decrease in the level of phosphatidylinositol when
      compared to controls. The phospholipid changes found in female null mice were
      associated with increased levels of esterified 18:1n-9, 20:1n-9, 20:4n-6, and
      22:5n-3 FA in plasmenylethanolamine, 20:1n-9 in phosphaticlylinositol, and 18:0,
      18:1n-9, 18:3n-6, 20:1 n-9, and 20:4n-6 in phosphatidylserine. Increased levels
      of esterified 18:1n-9, 18:2n-6, 18:3n-6, and 20:1n-9 were also found in the
      phosphatidylethanolamine fraction despite its cellular content remaining
      unchanged. Brain phospholipid content in male PPARbeta-null mice did not differ
      from controls, but increased levels of 20:1n-9 in the phosphatidylinositol and
      18:1n-9 in the phosphatidylserine fractions were observed. No changes were found
      in the content of brain cholesterol, TAG, and FFA in either female or male
      PPARbeta-null mice. These data suggest that PPARbeta is involved in maintaining
      FA and phospholipid levels in adult female mouse brain and provide strong
      evidence that suggests a role for PPARbeta in brain peroxisomal acyl-CoA
      utilization.

PMID- 12056593
TI  - Pancreatic beta-cell alpha2A adrenoceptor and phospholipid changes in
      hyperlipidemic rats.
AB  - We previously showed that a 48-h intravenous lipid infusion in rats induces
      pancreatic beta-cell hypersensitivity to catecholamines. Our aim was to study the
      lipid-related changes that may account for such hypersensitivity in pancreatic
      islets. We show here that a 48-h increase in plasma FFA alters the binding
      characteristics of beta-cell alpha2 adrenoceptors in rats. Lipid infusion
      decreases pancreatic norepinephrine (NE) turnover rate by 28%, reflecting a
      reduction of pancreatic NE stores. Following lipid infusion, the density of
      alpha2 adrenoceptor binding sites is significantly lower and receptor affinity
      higher, both in islet homogenates (by three- and fivefold, respectively) and
      isolated whole beta-cells (by two- and sixfold, respectively). These changes
      correlate with the elevated insulin response to glucose found in lipid-infused
      rats. We also found a modification of islet phospholipid content, particularly in
      phosphoethanolamine species containing infused FA such as palmitate, oleate,
      stearate, and linoleate. This may account for the modifications in receptor
      affinity. These results suggest that hyperlipidemia-associated pathologies such
      as diabetes and obesity not only may result from alterations of metabolic
      pathways but also may be a consequence of early modifications in nervous firing
      rates and signal transduction pathways.

PMID- 12056594
TI  - Evidence of a tetradocosahexaenoic cardiolipin in some marine bivalves.
AB  - Separation of phospholipid classes in lipid extracts from the scallop Pecten
      maximus, the Pacific oyster Crassostrea gigas, and the blue mussel Mytilus edulis
      was conducted using HPLC. An isolated polar lipid fraction was found to contain a
      very high level of DHA, up to 80 mol% of the total FA. MS with electrospray
      ionization in the positive-ion mode, tandem MS (MS-MS) and multidimensional NMR
      spectroscopy were used to analyze the detailed chemical structure of this polar
      lipid fraction. The isolated fraction contained exclusively cardiolipin (CL)
      molecules, predominantly in a form with four docosahexaenoyl chains (Do4CL). To
      the best of our knowledge, this is the first time that such a CL form has been
      analytically characterized and described in these three bivalve species. This
      tetradocosahexaenoic CL is presumed to reflect a specific adaptation in bivalves
      that enhances the structural and functional mechanisms of biomembranes in
      response to variations in environmental conditions (temperature, salinity,
      emersion).

PMID- 12056595
TI  - Analysis of vitamin E and its oxidation products by HPLC with electrochemical
      detection.
AB  - A sensitive HPLC procedure with postcolumn reduction and electrochemical
      detection was developed for the analysis of vitamin E and its oxidation products,
      alpha-tocopherylquinone, epoxy-alpha-tocopherylquinones, and 8a-(lipid-dioxy)
      alpha-tocopherones. After the separation on a reversed-phase column, on-line zinc
      catalyzed reduction allowed the detection of alpha-tocopherylquinone and epoxy
      alpha-tocopheryl-quinones, whereas platinum-catalyzed reduction allowed the
      detection of 8a-(lipid-dioxy)-alpha-tocopherones. The lowest detectable level of
      each compound was about 0.2 pmol at the signal-to-noise ratio of 3. This method
      was applied to the detection of alpha-tocopherol products in peroxidized human
      plasma. When the plasma was peroxidized by the addition of a free radical
      initiator, peaks corresponding to alpha-tocopherylquinone, epoxy-alpha
      tocopherylquinones, and the addition products of alpha-tocopherol with peroxyl
      radicals derived from cholesteryl ester hydroperoxides and PC hydroperoxides were
      observed. The amount of these oxidation products in the plasma increased with the
      depletion of endogenous alpha-tocopherol. The results indicate that the method is
      useful to detect the oxidation products formed by the peroxyl radical-trapping
      reactions of alpha-tocopherol in biological systems.

PMID- 12056596
TI  - A convenient method for determination of the C20-22 PUFA composition of
      glycerolipids in blood and breast milk.
AB  - A convenient method was developed for preparation of FAME in small amounts from
      glycerolipids of blood or breast milk. Initially, 0.04-0.06 mL blood or breast
      milk was spotted onto a small piece of filter paper (1.5 x 1.5 cm) that had been
      washed with acetone containing 0.05% 2,6-di-tert-butyl-p-cresol (BHT). Each
      piece, once it had dried, was put in a small test tube, to which 2 mL hexane and
      0.2 mL 2 M KOH/methanol were added. After vigorous mixing or sonication for 2 min
      at room temperature, the solution was neutralized or acidified by the addition of
      a few drops of acetic acid. To the solution was added 2 mL H2O, and then the
      hexane layer that separated was concentrated to dryness in vacuo. The FAME
      obtained were analyzed by GC. The method was applicable to the analysis of a
      large number of blood and breast milk samples, and the
      arachidonate/(eicosapentaenoate + docosahexaenoate) ratios could be determined
      rapidly.

PMID- 12056597
TI  - Base-catalyzed derivatization methodology for FA analysis. application to milk
      fat and celery seed lipid TAG.
AB  - In this paper, an alternative base-catalyzed methodology for the facile
      derivatization in mild conditions of lipid TAG prior to FA analysis is proposed.
      Reagents were prepared by proton exchange between potassium tert-butoxide and
      either ethanol, n-propanol, n-butanol, or 2-methoxyethanol and used for the
      synthesis, at 40 degrees C for 15 min, of the corresponding derivatives, which
      were directly analyzed by GC. This methodology can be used on a routine basis and
      has been applied to standard and complex natural lipid samples. Tripalmitin was
      used to determine optimal reaction conditions; and bovine milk fat, containing C4
      to C22 acids, and celery (Apium graveolens) seed oil, characterized by a high
      level of petroselinic acid, were comparatively analyzed as their ethyl, n-propyl,
      n-butyl, and 2-methoxyethyl esters.

PMID- 12056598
TI  - Decreased density of the CCR5 receptor on the surface of CD4+ lymphocytes and
      monocytes/macrophages is associated with the CCR5-59653T transition in the
      promoter region.
AB  - We compared the density of the CCR5 receptor on the surface of CD4+ lymphocytes
      and monocytes/macrophages of the homozygote (CCR5-59653C) and the heterozygote
      (CCR5-59653T), bearing CCR2-64V alleles. Flow cytometric analysis revealed lower
      density of the CCR5 receptor on the surface of CD4+ lymphocytes and
      monocytes/macrophages of the heterozygote than in the same cells of the
      homozygote. Our observation might explain slower replication of HIV and the delay
      in progression to AIDS in the individuals bearing CCR5-59653T transition.

PMID- 12056599
TI  - Reactivity of alveolar macrophages in lung cancer patients and healthy subjects:
      surface ICAM-1 after INF-gamma stimulation in vitro.
AB  - The linearity of ICAM- I expression on alveolar macrophages (AM) before and after
      INF-gamma stimulation in healthy and lung cancer subjects were compared. AM were
      collected by bronchoalveolar lavage and incubated with/without INF-gamma
      according to standard procedures. The harvested cells were analyzed by flow
      cytometry using monoclonal antibodies against leucocytes and macrophages. Only
      viable cells were analyzed. Stimulation with INF-gamma revealed two AM
      subpopulations of similar size differentiated in the intensity of ICAM-1
      expression. They were not distinctly marked in every studied case. Our
      preliminary results did not confirm the previously reported decreasing reactivity
      of AMs after INF-gamma stimulation in lung cancer patients.

PMID- 12056600
TI  - DNA ploidy assessment method applied to primary breast carcinoma FNA biopsies.
AB  - The goal of our study was to assess suitability of FNA biopsy material as a
      source of samples (cell suspension) for DNA ploidy assessment in neoplastic
      tumors using flow cytometry. DNA ploidy is an established prognostic factor in
      many types of cancers. Aneuploid breast tumors are characterized by increased
      aggressiveness which manifests itself through rapid local progression and
      metastatic spread. Investigated specimens were breast cancer FNA biopsy cell
      suspensions. Measurements were performed using flow cytometry. Material studied
      comprised 143 cases analyzed in 1999-2000. We found in this group 101 carcinoma
      cases with aneuploid type and 42 cases of primary breast carcinoma with diploid
      type of cell cycle. Immunocytochemical assesssment of estrogen receptor and
      progesterone receptor status was performed in group of 105 cases. DNA ploidy was
      compared to receptor status of the investigated cells. DNA aneuploidy correlated
      with weak or no reaction for the presence of estrogen and progesterone receptors.
      Our study demonstrates the suitability of DNA ploidy assessment method applied to
      cytological material from FNA biopsies.

PMID- 12056601
TI  - Fluorescence in situ hybridization (FISH)--application in research and
      diagnostics.
AB  - The methods of molecular cytogenetics, in particular fluorescence in situ
      hybridization (FISH), are widely applied in cytogenetics for identification of
      numerical and structural chromosomal abnormalities, which are difficult to detect
      by routine cytogenetic techniques. Due to many advantages, FISH is used in
      research (gene mapping, gene expression studies, interspecies chromosome
      homology), and clinical diagnostics (chromosomal aberrations analysis in pre- and
      postnatal diagnostics, oncology). The techniques of in situ hybridization (ISH)
      are often employed in addition to classical banding techniques, in case where
      banding pattern is not reliable. This paper focuses on particular clinical
      examples, where FISH was successfully used to identify structural and numerical
      chromosomal aberrations.

PMID- 12056602
TI  - The influence of photodynamic reaction on R2C cells.
AB  - Photodynamic therapy (PDT) represents a therapeutic approach in which
      photosensitised neoplastic cells undergo destruction under effect of light. In
      this study we have attempted to define effects of photochemotherapy on R2C cells,
      sensitised with protoporphyrin IX (PpIX) and to find out whether inhibition of
      gene expression by cycloheximide affects development of lesions in the cells. The
      photosensitised cells were exposed to visible light and development of apoptotic
      and necrotic lesions was followed in the cells, using the fluorescent staining
      with propidium iodide and Hoechst 33342. The experiments demonstrated that PpIX
      and light, acting in parallel, induce development of apoptotic and necrotic
      lesions in R2C cells. Intensity of the lesions correlated with concentration of
      the applied photosensitiser and with duration of light exposure. Using
      cycloheximide, we also inhibited protein expression in cells photosensitised with
      protoporphyrin before they were exposed to light. In the latter case, development
      of apoptosis was clearly intensified which might be explained by inhibition of
      anti-apoptotic protein synthesis in the cells.

PMID- 12056603
TI  - Plasma membrane translocation of phosphatidylserine in human spermatozoa.
AB  - The purpose of the study was to examine the phosphatidylserine translocation in
      human spermatozoa membrane during capacitation. Material consisted of human semen
      from normozoospermic men. Spermatozoa were stained with fluorescein-labelled
      annexin V. The presence and distribution of annexin V binding sites were analysed
      using the fluorescence microscope. Within first 60 min afterejaculation, 5-39%
      viable annexin V-positive spermatozoa were detected. The annexin V binding sites
      were found mainly in the midpiece. After 4 to 8 h of incubation of spermatozoa in
      capacitation medium (BMI), the number of cells positively stained with annexin V
      increased. After capacitation, the localisations of phosphatidylserine was
      changed and the annexin V binding sites were found also in the acrosomal region
      but never in the equatorial area. The process of the phosphatidylserine
      translocation observed during our experiments may reflect changes of the plasma
      membrane occurring during capacitation or, less likely, apoptosis of spermatozoa.

PMID- 12056604
TI  - The influence of storage time upon the real thickness of the histological brain
      sections.
AB  - The aim of the study was to assess the effect of storage time on the actual
      thickness of the histological sections. The study was performed on 5 brains of
      adult Wistar rats. The most rapid changes occur at the beginning of the storage
      process, after about one month the dynamics of changes decreases, but still the
      thickness of the sections diminishes. It is suggested that quantitative analyses
      should be performed in similar period of time and the critical care should be
      taken not only of the chemicals and procedures used, but also of the control of
      environmental factors.

PMID- 12056605
TI  - Relation between the age of specimen and the shrinkage of brain frozen sections.
AB  - The aim of the study was to assess the effect of age of the animal upon the real
      thickness of the frozen sections. The study was performed on 19 rabbit brains.
      The thickness of the frozen sections regardless of their staining is age
      dependent. The relation is proportional during the period from 7 to 180 postnatal
      day and characterizes both immunohistochemical as well as cresyl violet-stained
      sections; moreover, changes of the section thickness proceed parallelly. It is
      suggested that especially for some stereological parameters all required
      procedures should be standardized to achieve comparable and unbiasedly
      interpretable results.

PMID- 12056606
TI  - Advances in immunocytochemistry.
AB  - Recent advances in immunohisto/cytochemical methods have been directed towards
      new fluorescent labels, and to increasing sensitivity and improving methods for
      multiple immunostaining. The newest fluorescent dyes come in many colours, are
      much more stable than fluorescein isothiocyanate and give brighter fluorescence.
      The greatest impact on sensitivity comes from heat-induced antigen retrieval on
      paraffin sections. Biotinylated tyramide can also increase enormously the amount
      of label on a preparation. The immunogold method with silver enhancement has been
      improved by nanogold, which is smaller than colloidal gold, attracts more silver
      and increases the sensitivity even further. The difficulties of multiple
      labelling with two or more primary antibodies raised in the same species due to
      cross-binding between reagents have largely been overcome. There are new methods
      of blocking spare reactive sites on the first reaction by strong heat, e.g. from
      microwaving in buffer. Alternatively, one of the antibodies can be directly
      biotinylated very easily with a new commercially available kit.

PMID- 12056607
TI  - Comparison of techniques permitting to detect apoptosis in situ.
AB  - Several morphological and biochemical techniques are in use for identification of
      apoptotic and necrotic cells in a studied cell population. It is essential to
      define not only the type of cell death but also to identify the apoptotic process
      itself, which represents a multistage, active process, requiring activation of a
      molecular event cascade. In the present study, we have examined and discussed
      effectiveness of the selected techniques detecting apoptosis in lymphocytes
      exposed to incubation at an elevated temperature. The appraisal involved
      detection of caspase-3 active form, detection of Bcl-2, TUNEL reaction, the comet
      assay and electrophoresis of DNA.

PMID- 12056608
TI  - Correlation of histopathological and biochemical appraisal of anthracyclin
      induced myocardium damage.
AB  - Treatment of various tumor types with anthracycl in cytostatic drugs (DNR-
      daunorubicin and DOX--doxorubicin) is limited by their high cardiotoxicity. This
      study was aimed at examining effectiveness of histopathological appraisal of
      myocardial cell injury induced by the cytostatic drugs and evaluated according to
      Billingham and by MTS methods as compared to results of parallel biochemical
      assessment of lipid peroxidation indices (MDA- malonyldialdehyde, 4-HDA-4
      hydroxyalkenes). The experiments were performed on rats intoxicated with DNR or
      DOX in an acute manner (1 x 10 mg/kg body weight, i.v.) or a subchronic manner (3
      x 3 mg/kg body weight. i.v.). Significant positive correlations were demonstrated
      between results of histological and biochemical appraisal in rats intoxicated in
      the acute manner with DNR (r=(0.91), intoxicated in the subchronic manner with
      DNR (r=0.90) and in rats intoxicated in the acute or subchronic manner with DOX
      (r=0.91, r=0.77, respectively). The obtained results have confirmed the free
      radical mechanism of cardiomyocyte injury induced by anthracyclines and the
      applied techniques of evaluating the destruction may be used independently of
      each other.

PMID- 12056609
TI  - Value of PCR technique in detection of Helicobacter pylori in paraffin-embedded
      material.
AB  - Methods which permit effective detection of Helicobacter prlori are based on
      endoscopic sampling of gastric mucosa followed by a direct or indirect
      demonstration of Helicobacter pylori bacilli, e.g. searching for specific
      proteins or gene fragments. PCR technique represents one of techniques employed
      for diagnosing the biopsies. The present study was aimed at examining how
      effective is the detection of Helicobacter pylori in paraffin-embedded material
      by PCR technique using primers for the Ure C gene fragment. The material for
      studies involved gastric biopsies, routinely fixed in formalin and embedded in
      paraffin. In order to perform PCR, DNA was isolated and purified, subjected to
      amplification with the use of starters for the Ure C gene fragment. The performed
      experiments have confirmed suitability of PCR technique for detection of
      Helicobacter pylori.

PMID- 12056610
TI  - Sequential translocation of tyrosine kinases Lyn and Syk to the activated Fcgamma
      receptors during phagocytosis.
AB  - Tyrosine phosphorylation of numerous proteins is one of the earliest events
      detectable during Fcgamma receptor-mediated phagocytosis. We demonstrate that IgG
      coated particles associated with the surface of macrophages are enriched with
      numerous tyrosine-phosphorylated proteins. During particle internalization the
      proteins are still associated with particles but their phosphorylation is
      reduced. Lyn kinase is phosphorylated both at particle binding and
      internalization steps. The phosphorylated Syk kinase is the major kinase
      associated with engulfed particles. Imnunofluorescent studies confirm spatial and
      temporal distribution of Lyn and Syk kinases at different stages of phagocytosis.
      Our data indicate that ligation of Fcgamma receptors activates Lyn followed by
      Syk kinase and in the result multimolecular complex of the kinases and several
      accompanying tyrosine phosphorylated proteins with Fcgamma receptors is organized
      leading to local reorganization of actin-based skeleton and particle uptake.

PMID- 12056611
TI  - Efficiency of lipofection of adherent cells is limited by apoptosis.
AB  - Stability of gene expression and transfection efficiency plays the main role in
      the application of gene transfer method. In somatic cell gene delivery,
      expression of the gene product is limited by the function of the cell to which it
      is delivered. In the present study analyzing the lipofected adherent cells, we
      have shown that lower level of transgene: beta-galactosidase activity at later
      time period correlated with decrease in cell viability, which was shown to be due
      to apoptosis. Apoptosis following DNA uptake occurred only when DNA was present
      during lipofection.

PMID- 12056612
TI  - Effects of the combination of a proteasome inhibitor (PSI) and an inhibitor of
      ubiquitin-ligases (Leu-Ala) on the ultrastructure of human leukemic U937 cells.
AB  - We have used the dipeptide Leu-Ala in an attempt to prevent the formation of
      ubiquitin-protein conjugates in U937 cells by inhibition of cellular E3 enzymes
      (ubiquitin ligases). Proteasome inhibitors induce the formation of perinuclear
      aggregates of ubiquitinated proteins and proteasomes (aggresomes) in the area of
      the proteolytic center of the cell. Leu-Ala did not prevent the forrmation of
      those aggregates under the action of PSI (peptidyl aldehyde, selective inhibitor
      of the chymotrypsin-like activity of the proteasome), however it induced an
      accumulation of lipid droplets in treated cells, suggesting a previously unknown
      involvement of Leu-Ala in lipid metabolism. We conclude, that either Leu-Ala is
      not able to completely inhibit the cellular E3 enzymes or some of those enzymes
      are insensitive to this dipeptide, allowing therefore the build-up of ubiquitin
      conjugates in the proteolytic centre of the cell.

PMID- 12056613
TI  - The effect of quercetin on the expression of heat shock proteins and apoptosis
      induction in monkey kidney cell line GMK.
AB  - The present study was designed to investigate whether quercetin, a very common
      flavonoid widely distributed in many plants, can induce apoptosis in monkey
      kidney cells (GMK). Involvement of the expression of heat shock proteins Hsp72,
      Hsp73, Hsp27 and the significance of cell culture model in this process were also
      examined. The studies have shown that quercetin alone and in combination with the
      heat shock can induce apoptosis and necrosis in vitro in the studiedcells, but
      the percentage of affected cells did not exceed 3.9%. In the same experimental
      conditions, the expression of Hsp 73, Hsp72 and Hsp27 increased in cells cultured
      in two-dimensional system and decreased in three-dimensional model. This
      indicates that strong inhibition of heat shock proteins in GMK cells is not
      correlated with an adequate increase in the sensitivity of cells to undergo
      apoptosis. It also shows that the sensitivity on the manifested by Hsp expression
      and apoptosis induction, depends on the culture model and culture conditions.

PMID- 12056614
TI  - The expression of PDGF, its receptors and capillary morphometry in the developing
      lung: quantitative studies.
AB  - The aim of the present study was the evaluation of the expression levels of PDGF
      A and B, and PDGFR-alpha, andchanges of capillary cross-sectional areas during
      terminal vascular network formation in the developing lung. Pathogen-free fetuses
      and newborns used for rats were used. Lungs were processed for frozen section
      immunohistochemical staining and parallel tissue specimens were prepared for
      transmission electron microscopy. The expression levels of PDGF-A and B, and
      PDGFR-alpha were obtained using quantitative image analysis. Additionally. the
      morphometry of capillary cross-sectional area was performed. We found that the
      expression levels of the studied antigens fluctuated, and the highest values were
      found in21-day old fetuses (p < 0.0001). Although there were no significant
      differences of the area of "a single" capillary, the area of the endothelium
      decreased significantly in perinatal period (p <0.0001). We conclude that the
      statistically significant changes of the studied antigens' expression as well as
      the of capillary cross-sectional area occur in the perinatal period,

PMID- 12056615
TI  - Immunoreactivities of eNOS, ET-1 and ETB-R in blood vessels of the uterine
      mesometrium during the estrous cycle in the pig.
AB  - Cryostat sections of arterial and venous vessels from various size branches of
      the uterine artery and utero-ovarian vein of the pig mesometrium in different
      phases of the estrous cycle were stained immunohistochemically for endothelial
      nitric oxide synthase (eNOS), endothelin-1 (ET-1) and endothelin B receptor (ETB
      R) using ABC method. Immunoreactivity was evaluated according to 6-point scale
      under light microscope. The differences in immunostaining intensity in the
      endothelium of the vessels studied at various levels of mesometrium suggest a
      correlation of eNOS, ET-1 and ETB-R expression with the estrous cycle. In the
      follicular phase, the highest eNOS immunoreactivity was noticed in arcuate
      arteries and veins, while immunoreaction of ET-1 was much lower, just as ETB-R.
      On the other hand, the highest ET-1 immunoreactivity was observed during first 2
      days afterovulation, while ETB-R showed low immunoreactivity level during the
      whole luteal phase. Vessels from the middle part of mesometrium (I degrees and II
      degrees branches) and large vascular trunks revealed similar staining for eNOS
      during the cycle as compared to arcuate arteries. Those vessels showed very high
      immunoreactivity levels for ET-I and ETB-R during first 2 days after ovulation.
      Our results suggest that during the estrus eNOS, ET-I and ETB-R play a
      significant role in the regulatory process of blood flow through the mesometrial
      vessels, that are connected to the uterine horn.

PMID- 12056617
TI  - Distribution of NADPH-diaphorase activity in the pineal gland of the Turkey.
AB  - NADPH-diaphorase activity was histochemically demonstrated in the nerve fibers,
      neuronal-like cell bodies and in the endothelial cells of the vasculature in the
      pineal gland of the turkey. The nerve fibers were localized in the choroid
      plexus, connecting the pineal gland with the diencephalon as well as inside the
      pineal gland, where they formed basket-like structures around the pineal
      follicles. A group of neuronal-like cell bodies was observed in the proximal part
      of the gland. The positive staining was not observed in the pinealocytes of
      rudimentary-photoreceptor type and in the supporting cells.

PMID- 12056616
TI  - Histochemical localization of NADPH-d-positive structures in bovine uterine and
      ovarian arteries during the oestrous cycle and early pregnancy.
AB  - The aim of the present study was to histochemically demonstrate nitric oxide
      synthase-related NADPH-d activity in ovarian and uterine arteries of heifers at
      different stages of the oestrous cycle and during early pregnancy. Catalytic
      activity of NADPH-d activity was found in the endothelial lining of all examined
      vessels, however, staining intensity was higher in the segments ipsilateral to
      the corpus luteum than in those taken from the contralateral side. Moreover, the
      reaction was much more intense during the luteal than during the follicular stage
      of the cycle. Similar differences were observed for NADPH-d activity in the
      muscular coat. In conclusion, the present results suggest that the
      endothelial/muscular cells may be the main source of nitric oxide in the studied
      parts of the bovine arteries, and also that NADPH-d activity may depend on the
      hormonal status of the organism.

PMID- 12056618
TI  - Leu-enkephalin immunoreactivity in the pig pineal gland.
AB  - Leu-enkephalin-positive structures in the pig pineal gland were demonstrated
      immunohistochemically using mouse monoclonal antibody. The pineal glands were
      obtained from the newborn, 21-day and 7-month old female pig. The immunopositive
      nerve fibers were observed in the pineal gland as well as in the epithalamic
      areas. The leu-enkephalin-immunoreactive nerve fibers (single or forming small
      bundles) were localized mainly in the proximal part of the pineal and they were
      scarce in other parts. The localization of the fibers points to a central source
      of this innervation. The study did not show any age-dependent differences in the
      distribution and density of leu-ekephalin-positive nerve fibers.

PMID- 12056619
TI  - Pituitary adenylate cyclase-activating polypeptide-immunoreactive (PACAP-IR)
      nerve fibers in the pig pineal gland.
AB  - The present study demonstrates the occurrence of PACAP-immunoreactive (PACAP-IR)
      nerve fibers in different compartments of the pig pineal gland, including
      glandular capsule (where they form a very dense network) and subependymal tissue
      close to the pineal recess (moderate to dense meshwork of varicose fibers).
      Furthermore, several varicose fibers penetrate from the capsule into the
      connective tissue septa and then into the parenchyma, where they form unequally
      distributed, fine network and, in some cases, basket-like structures around
      pinealocytes. Some of the PACAP-IR nerve fibers, observed both in the habenular
      and posterior epithalamic areas, extend to the pineal gland. PACAP-IR cells could
      be demonstrated neither in the pineal gland, nor in epithalamic areas.

PMID- 12056620
TI  - Neither axotomy nor target-tissue inflammation changes the NOS- or VIP-synthesis
      rate in distal bowel-projecting neurons of the porcine inferior mesenteric
      ganglion (IMG).
AB  - The present study was aimed at disclosing axotomy- and inflammation-induced
      changes in the chemical coding of retrogradely labelled distal bowel-projecting
      neurons in the porcine IMG. Particular attention was paid to the changes in the
      expression pattern of vasoactive intestinal polypeptide and nitric oxide synthase
      (as a marker of nitric oxide) in affected cells, as these substances are thought
      to play a crucial role in the regeneration of injured sympathetic neurons.
      However, while both pathological processes failed to induce an increase in the
      number of sympathetic bowel-projecting neurons exhibiting vasoactive intestinal
      polypeptide or nitric oxide synthase, axotomy, but not target-tissue
      inflammation, led to the upregulation in the expression pattern of galanin,
      pituitary adenylate cyclase-activating peptide and/or Leu5-enkephalin in the
      affected perikarya. On the other hand, axotomy resulted in a diminished density
      of vasoactive intestinal polypeptide-immunoreactive intraganglionic nerve fibres,
      whilst target-tissue inflammation evoked a distinct increase in the number of
      visible vasoactive intestinal polypeptide-immunoreactive terminals, especially in
      those regions where bowel-projecting neurons were located. Thus, the data
      obtained in the present study run counter to the results of the injury-related
      responses observed in neurons of the sympathetic chain ganglia, suggesting the
      existence of either species- or target tissue-dependent differences in the injury
      induced responses of the affected sympathetic neurons.

PMID- 12056621
TI  - A search for colocalization of mglula receptors with CRF or NPY in the rat brain
      amygdala.
AB  - Excitatory neurotransmitter glutamate, as well as corticoliberin (CRF) and
      neuropeptide Y (NPY) play an important role in fear and anxiety. Among the brain
      structures engaged in these effects the important one is amygdala. In the present
      study, a single and double immunohistochemical staining techniques were used in
      order to visualize CRF, NPY and metabotropic glutamate receptors (mGluR1a) in rat
      amygdala. MGluR1a belongs to class of postsynaptic excitatory receptors and has a
      preferable somatic localization. CRF and NPY were localized using rabbit
      polyclonal antibodies, and mGluR1a using a mouse monoclonal one. Then, ABC
      peroxidase and DAB or benzidine were used. Upon single immunostaining, NPY and
      CRF were found in some nerve cell bodies and fibres in the amygdala. The
      immunoreactivity of mGluR1 a was observed in some nerve cells, processes and
      fibres, especially on the border between the central and the basolateral nuclei
      and ventrally to that region. Double staining revealed mGluR1 a-IR on some CRF-
      and NPY-immunoreactive nerve cell bodies and processes. The obtained results
      indicate that mGlu1a receptors may control at least some NPY and CRF neurons in
      the amygdala.

PMID- 12056622
TI  - Boar pheromone androstenol may affect the ovarian morphology in cycling gilts by
      humoral pathway.
AB  - Up to 1999 it was accepted that pheromones act exclusively by stimulation of
      dendritic receptors of olfactory neurons massed in the olfactory epithelium, but
      in 1999-2000, the presence of local humoral pathway for transfer of boar
      pheromone androstenol from the nasal cavity to the hypophysis and brain was
      demonstrated in gilts. The aim of the present study was to ascertain whether boar
      pheromone androstenol may affect by humoral pathway the ovarian morphology in
      gilts. This study demonstrated that intramuscular injections of androstenol in
      the follicular phase (17-20 day) of the estrous cycle in anosmatic gilts, in
      which the neural pathway for olfactory function was experimentally blocked,
      produced lack of the ovulation and changes in the morphology of ovaries.
      Histological analysis of the ovaries, collected seven days after androstenol
      injections, revealed the absence of corpora lutea and healthy follicles of a
      diameter over 6 mm as well as a significant decrease in the number of the
      follicles up to I mm in diameter (P<0.01). In androstenol-treated gilts, the
      number of atretic follicles from 1 mm to 6 mm in size was increased (P<0.01
      P<0.001) and in one gilt cysts were found. The obtained results provided some
      evidence that in gilts in addition to acting by standard neural pathway,
      androstenol as a priming pheromone may affect the ovarian morphology by a humoral
      pathway.

PMID- 12056623
TI  - The structure of the spiny mouse (Acomys cahirinus) ovary during development.
AB  - The study presents the structure of the ovaries of the spiny mouse (Acomys
      cahirinus) during the first months of life. The ovaries in neonate females
      exhibit a large number of primordial and primary follicles, sometimes clustered
      in nests. The growing follicles were also observed within the ovary at that
      period. The first, early antral follicles appeared in the ovary during the second
      week of life. In the group of 60-day old females, the structure of the ovaries
      was characterized by a significant increase in the connective tissue elements.
      Moreover, ovarian follicles at various stages of development were observed,
      except for the antral ones with cumulus oophorus. The first mature follicles were
      identified in 3-month old females. In the ovarian follicles, apoptosis occurs at
      all stages of follicle development, especially in the early antral follicles. In
      the atretic follicles, apoptotic cells were identified in the layer of granulosa
      cells.

PMID- 12056624
TI  - The influence of interleukin-1 and interleukin-6 on expression of proteins
      involved in steroidogenesis in Leydig cells and on their apoptosis or necrosis in
      vitro.
AB  - This paper presents a study on the expression of proteins involved in
      steroidogenesis in rat Leydig cells: StAR protein and aromatase, in relation to
      the age of animals and to the influence of interleukin-1 and interleukin-6. In
      addition, their effect on apoptosis and damage of Leydig cells was investigated.
      Leydig cells were isolated from rats at certain age intervals and exposed to
      different concentrations of the above-mentioned cytokines. Next, total RNA was
      isolated from Leydig cells and RT-PCR with primers specific for rat StAR protein
      and aromatase was performed. The products were analysed by agarose gel
      electrophoresis. Leydig cells were also stained with propidium iodide and Hoechst
      33342 to estimate the percentage of apoptotic or necrotic cells. The results seem
      to confirm the role of interleukins in the control of expression of enzymes and
      regulatory factors involved in steroidogenesis in rat Leydig cells, and in the
      regulation of their apoptosis and necrosis. The effect of the studied
      interleukins on Leydig cells is exerted during development and after adolescence.

PMID- 12056625
TI  - Immunohistochemical localization of androgen receptors in testicular cells of
      mice with mosaic mutation.
AB  - Mice with mosaic mutation could be one of the models of human Menkes disease,
      which is associated with abnormal cooper metabolism. The aim of the present study
      was to localize androgen receptors (ARs) in the testes by means of
      immunohistochemistry. AR expression was observed in the nuclei of all somatic
      cells such as Leydig cells, Sertoli cells, and peritubular cells in sections from
      testes of control and mosaic mutant males. In the latter, very strong
      immunoreactivity for AR as well as higher levels of steroid hormones in
      homogenates were noticed in comparison to control mice. No positive
      immunoreaction for ARs was seen in control sections incubated without the primary
      antibody.

PMID- 12056626
TI  - Germ cells with nuclear DNA fragmentation related to apoptotic cells in rat
      testis in experimental hyperprolactinemia induced by metoclopramide.
AB  - The cells with nuclear DNA fragmentation related to apoptosis were detected by
      TUNEL technique in the seminiferous epithelium of control rats and of rats with
      experimental hyperprolactinemia induced by metoclopramide. The percentage of
      convoluted tubules with apoptotic cells and the number of apoptotic cells
      (predominantly spermatogonia and spermatocytes) was increased in the experimental
      group. The results indicated stage-specific germ cell apoptosis. In the
      experimental group, apoptotic cells were most evident at early (I-IV), middle
      (VII-VIII) and late (XII-XIV) stages of the seminiferous epithelium cycle, as
      revealed by light and electron microscopy. We suggest that a decreased
      concentration of testosterone and an increased concentration of prolactin could
      disturb spermatogenesis and contribute to the intensive apoptosis of germ cells
      in rats with hyperprolactinemia. Sertoli cells which have receptors for
      testosterone and prolactin and play an important role in spermatogenesis and in
      the initiation of apoptosis in seminiferous epithelium, could mediate such an
      influence of both hormones.

PMID- 12056627
TI  - New method of quantitative analysis of seminiferous epithelium in male guinea
      pigs.
AB  - The aim of the study was the comparison of a newly developed method of
      quantitative analysis of the seminiferous epithelium (SE) cells with the
      traditional method based on stage classification according to Clermont. In 4000
      sections of seminiferous tubules the following parameters have been evaluated: in
      procedure I--the frequency of cells at the particular stages of the SE cycle, in
      procedure II--the frequency of particular cell types forming SE. In the two
      procedures, 17,726 and 14,670 cells were assessed, respectively. In both
      procedures, the mean values of the studied cells per animal (I--886.3 +/- 15.4;
      II--733.5 +/- 96.9) and the distribution of the particular types of cells were
      similar. The new method of quantitative analysis is less laborious and cheaper.
      It may be applied instead of the method used so far.

PMID- 12056628
TI  - Temperature dependent hysteresis-like changes of motility parameters in human
      spermatozoa.
AB  - We studied the impact of temperature changes on selected parameters of
      normozoospermic spermatozoa motility. The examinations were carried out in the
      temperature range of 11 degrees C to 21 degrees C both during cooling and
      heating. We found that a phenomenon of hysteresis, i.e. alternate means of
      changes in velocity straight linear and lateral head displacement was obtained
      both at cooling and at heating. This phenomenon was not found for other
      parameters examined.

PMID- 12056629
TI  - Proteasome localization and ultrastructure of spermatozoa from patients with
      varicocele--immunoelectron microscopic study.
AB  - Localization of proteasomes in spermatozoa from patients with varicocele
      associated sterility was studied by means of immunolabeling with the MPC21
      monoclonal antibody detecting the C3 subunit of the 20S proteasome. The reaction
      was visualized for electron microscopy using the secondary Nano-Gold-coupled
      antibody with Gold-Enhancement in pre-embedding technique. We found that semen
      samples from varicocele patients contained a large amount of abnormal spermatozoa
      characterized by the presence of dispersed chromatin and large residual bodies
      (cytoplasmic droplets) as well as spermatids at various stages of spermiogenesis.
      In normal spermatozoa, the immunolabeling was found in the acrosome,
      postacrosomal regions, nuclear vacuoles, in the neck and in the middle-piece as
      well as in the residual bodies, while chromatin remained unlabeled. In varicocele
      spermatozoa, the immunolabeling was also associated with chromatin and large
      residual bodies (cytoplasmic droplets). In contrast to normal, mature
      spermatozoa, the chromatin of the cells at earlier stages of spermiogenesis was
      strongly immunolabeled. The association of proteasomes with sperm chromatin and
      large residual bodies can be the sign of abnormality and disturbances in
      spermatogenesis associated with varicocele.

PMID- 12056631
TI  - Age-related changes in rat thymic epithelial cells.
AB  - We investigated age-related changes in immunocytochemical localisation of
      cytokeratin 16 (CK16) in thymuses of female Wistar rats at various stages of
      adult life (months 1, 3, 6, 12). Within the 1 st month of life, distribution of
      CK typical for individual subsets of thymic epithelial cells (TEC) was observed.
      The most numerous CK16+ TEC were observed in the outer region of medulla, in the
      outer cells of Hassall's corpuscles and in the superficial epithelial layer
      neighbouring the connective tissue of the capsule, septa and vessels of the
      thymus. In the 3rd month of life, increased intensity of CK16 reaction in
      superficial TEC was accompanied by increased numbers of CK 16+ TEC in the outer
      region of the medulla. Age-related alterations in the distribution of the studied
      markers were evident beginning from the 6th month of life and involved increased
      expression of CK16 in the superficial layer of TEC, which at the interface with
      the septa formed stratified epithelium. In parallel, decreased numbers of CK16+
      TEC were observed in the outer region of the medulla. Changes in CK16+ TEC
      distribution of a similar type developed in 12-month old rats and they probably
      reflected altered functions of some TEC populations and decreased or increased
      biological activity of other TEC populations.

PMID- 12056630
TI  - Stages of the rat thymic medulla development in foetal period.
AB  - Development of thymic medulla was examined on consecutive gestational days (GD)
      in Wistar rats. Medullary thymic epithelial cells (TEC) were identified by
      immunocytochemical localisation of neuron-specific enolase (NSE). Organisation of
      thymic medullary architecture was determined by interaction of thymocytes with
      NSE-positive TEC, that led to formation of lymphoepithelial complexes (GD 19), in
      which the cells exhibited proliferative activity or traits of apoptosis. The
      studies indicated that differentiation events and organisation of thymic medulla
      require stage-specific interactions between TEC and thymocytes.

PMID- 12056632
TI  - Lympho-epithelial interactions in rat thymus during pregnancy.
AB  - Alterations in the thymic epithelial cell activity were analysed during pregnancy
      and lactation in Wistar rats by examining the presence and in situ distribution
      of lymphoepithelial complexes formed by thymic nurse cells (TNC). TNC were
      identified in paraffin sections by their expression of MHC class II antigens,
      CD54 molecule and a neuromarker, protein gene product 9.5 (PGP9.5). On the first
      days of pregnancy (gestational days, GD) the number of PGP9.5+ TNC was found to
      decrease abruptly. On GD 14, a transient increase was noted in the number of
      PGP9.5+, MHC+, CD54+ TNC. Another increase was observed in the course of
      lactation, when the weight of the thymus reached the lowest values. While the
      increase in TNC numbers during lactation may be linked to the process of
      reconstruction of the thymic lymphoid population, the augmented activity of
      lymphoepithelial interactions on GD14 may be associated with thymic engagement in
      pregnancy-induced immune processes.

PMID- 12056633
TI  - The dynamics of morphological changes in the pyloric endocrine cells of rats with
      uremia.
AB  - Disturbances in renal homeostatic function lead to changes in endocrine cell
      secretory activity. The aim of this study was the histomorphological estimation
      of dependence of gastric APUD system cell morphology and function on the time
      after subtotal nephrectomy in Wistar rats. Fragments of gastric pylorus were
      collected 1. 2, 4, and 6 weeks after nephrectomy. Paraffin sections were stained
      with H+E and by silver impregnation. Immunohistochemical reactions with the use
      of specific antibodies against calcitonin gene-related peptide (CGRP),
      synaptophysin (SPh). somatostatin (ST), and neuron-specific enolase (NSE) were
      also performed. Immunoreactivity of the examined substances in the pyloric mucosa
      in the first week after nephrectomy was lower than in the control group. However,
      in the following time intervals, endocrine cells showed stronger immunostaining
      in comparison with the control rats. The results suggest that chronic renal
      failure can modulate secretory activity of APUD system cells.

PMID- 12056634
TI  - Preliminary evaluation of pancreatic islets in rats with experimental uremia and
      after thyroparathyroidectomy.
AB  - Hormonal disorders are the permanent symptoms of renal failure. They concern all
      known hormones and can be due to quantitative changes of the secretory activity
      and disturbances of endocrine cell functions. The aim of this study was to
      establish whether experimental thyroparathyroidectomy in uremic animals causes
      detectable histomorphological changes in endocrine cells of pancreatic islets.
      Thyroparathyroidectomy was performed in rats 30 days after nephrectomy. Fragments
      of pancreatic tissue were collected 14 days after the operation. Paraffin
      sections were stained with H+E and by silver salt impregnation.
      Immunohistochemical reactions were conducted using antibodies against
      calcitoningene-related peptide (CGRP), synaptophysin (SPh), somatostatin (ST),
      neuron-specific enolase (NSE), and chromogranin (CgA). It was shown that
      endocrine cells of pancreatic islets in thyroparathyroidectomized rats show
      intensified immunoreactivity to SPh and ST as compared to the control group of
      animals. Immunocytochemical reactions for NSE, CgA, and CGRP were negative.

PMID- 12056635
TI  - Thyroid C cells in male and female rats with chronic renal failure.
AB  - The kidneys are responsible for iodine and of thyroid hormone biodegradation. The
      aim of this study was the histomorphological and immunohistochemical evaluation
      of the influence of sex on parafollicular thyroid C cells in rats with chronic
      renal failure. The experiment included 40 Wistar rats after subtotal nephrectomy,
      after sham operation, and without any surgical procedure. Two weeks after
      nephrectomy, fragments of thyroids were collected from the examined animals.
      Paraffin sections were stained with H+E and by silver impregnation. Calcitonin
      (CT), synaptophysin (SPh), somatostatin (ST), and neuron-specific enolase (NSE)
      were detected immunohistochemically in C cells. In rats with experimental uremia,
      immunostaining for the examined substances increased significantly in comparison
      to the controls. We also observed higher number of C cells with a stronger
      reaction in the group of males, compared to the female rats.

PMID- 12056636
TI  - Hybridocytochemical detection of mRNA for calcitonin, CGRP, NPY and somatostatin
      in thyroid parafollicular (C) cells in three rodent species.
AB  - The present study was aimed at hybridocytochemical (HCC) detection and
      interspecies comparison of mRNA for calcitonin (CT), calcitonin gene-related
      peptide (CGRP), neuropeptide Y (NPY) and somatostatin (SS) in thyroid C cells of
      two rodent families of wild Microtidae: pine voles and common voles and also of
      laboratory Muridae, Wistar rats. Studies were performed on adult males. The HCC
      method in situ and immunomax technique were used to detect mRNA. DNA
      oligonucleotide probes labeled with digoxigenin were used in the HCC method. The
      obtained results were compared to the results of immunocytochemical (ICC)
      examinations, where rabbit or mouse antibodies against human CT, SS, NPY and rat
      CGRP, as well as chromogranin A were performed. In the present study, HCC
      reaction has demonstrated the presence of mRNA for CT and CGRP in all thyroid C
      cells in all the species examined. However, mRNA for NPY and SS was observed in
      very few C cells in rat and in many more C cells in the two species of wild
      rodents. The distribution of the positive cells corresponded with that of ICC
      detected cells.

PMID- 12056637
TI  - Thyroid C cell function during fasting and refeeding of young and old rats.
AB  - Age-related alterations in the structure and function of many organs often become
      apparent under stimulation of their function. Although the ageing process affects
      the regulation of mineral homeostasis, the function of thyroid C-cells that
      secrete calcitonin (CT) under the conditions of fasting and refeeding, a way of
      dietary manipulation that reveal the existence of age-related changes of
      follicular thyroid cells, has not been characterized. Therefore, we investigated
      the number of C-cells and serum CT concentration in young (4 mo) and old (26 mo)
      male rats fasted for 48 hours, and then refed for 4 or 24 hours. We found
      significantly higher number of C-cells in thyroids of old vs young rats both
      under basal conditions, and after fasting/refeeding. Correspondingly, serum
      calcitonin level was higher in fed or fasted old rats vs young ones. However, in
      young rats refeeding decreased, whereas in old animals increased serum
      concentrations of calcitonin. Thus, the control of serum calcium concentration,
      that was well preserved in old rats, occurs at the expense of increased serum CT
      level both under basal conditions, and after refeeding. These observations
      suggest that C-cell function is altered in ageing.

PMID- 12056638
TI  - Effect of calcitriol on proliferation of TT cells and on expression of calcitonin
      gene.
AB  - The absence of serum steroids was demonstrated to restrict proliferation of
      cultured TT cells (cell line originating from human thyroid medullary carcinoma)
      and supplementation with calcitriol was found to partially restore the
      proliferation. Calcitriol stimulated TT cell proliferation by augmenting
      expression of proliferation-associated proteins and by restricting apoptosis.
      Moreover, calcitriol decreased the intensity of transcription but failed to
      change direction of the altemate splicing of the calcitonin gene.

PMID- 12056639
TI  - Effect of chronic administration of cadmium on the rat thyroid:
      radioimmunological and immunohistochemical studies.
AB  - The effect of chronic (12 months) oral cadmium (Cd) administration (5 or 50 mg
      Cd/dm3) to rats on the structure and function of the thyroid was evaluated.
      Paraffin thyroid and parathyroid sections were stained with H+E and
      immunocytochemically for calcitonin (CT), somatostatin (ST), synaptophysin (SPh),
      chromogranin A (CgA) and thyroid transcription factor-1 (TTF-1). Serum levels of
      thyroid hormones: triiodothyronine (T3) and tetraiodothyronine (T4) as well as
      levels of Cd in the blood and calcium (Ca) in the serum were estimated. CT, ST
      and SPh were detected in C cells of the thyroid, while CgA in both thyroid and
      parathyroid cells. In animals exposed to Cd, proliferation of CT- and SPh
      positive thyroid C cells was observed, ST being found only in very few C cells-
      both in control animals and in those exposed to Cd. Serum T3 concentration was
      not affected by Cd, while T4 was reduced but only at the exposure to the higher
      Cd concentration. Moreover, the rats exposed to Cd showed a decrease in serum Ca
      concentration.

PMID- 12056640
TI  - Tumoricidal effect of macrophages on transplantable melanoma cells with regard to
      their sensitivity to exogenous cytokines.
AB  - We studied the correlation between the cytotoxic effect of hamster peritoneal
      macrophages from animals bearing transplantable melanomas of common origin but
      differing in many biological features on the cells of those melanomas and the
      sensitivity of the melanoma cells to exogenous OSM, TNF-alpha and IL6. Our
      results did not show such a correlation.

PMID- 12056641
TI  - Protein kinase C involvement in proliferation and survival of breast cancer
      cells.
AB  - Members of protein kinase C (PKC) family have been widely implicated in the
      regulation of cell proliferation, differentiation and survival. Increased protein
      C activity in malignant breast tissue and in most aggressive breast cancer cell
      lines suggests possible role of PKC in the development and progression of breast
      cancer. PKC may be therefore a target for breast cancer treatment. In our study
      we attempted to investigate the effect of: phorbol ester (PMA)-PKC activator, and
      bisindolylmaleimide II (GF II), a highly selective PKC inhibitor, on the
      proliferation as well as induction of apoptosis and necrosis in breast cancer
      cell line MDA-MB-231. Our results provide evidence for multidirectional effects
      of PKC on the proliferation of this type of breast cancer cells. The effects of
      both compounds were different after short time of exposition (1-3 h). PMA induced
      proliferation, while GF II showed an opposite effect. After 24 h, however, both
      compounds exhibited relatively high inhibitory effect on the proliferation and
      proved to be effective in induction of necrosis and apoptosis.

PMID- 12056642
TI  - Establishment and preliminary characterization of two cell lines derived from
      larynx carcinoma.
AB  - Two new cell lines, designated as RK-33 and RK-45, have been successfully
      established by an outgrowth technique from two different larynx tumours obtained
      from patients after laryngectomy. Both cell lineshave been maintained
      incultureforover 18 monthsandrecently have reached passage number 220 (RK-33) and
      110 (RK-45). The cells display an epithelial morphology and multiply with a
      population doubling time of about 24 h (RK-33) and about 40 h (RK-45). The
      epithelial nature of the cells was also confirmed by expression of cytokeratins 8
      and 18. Both lines were sensitive to antiproliferative effect of the tested
      cytostatic agents such as methotrexate. etoposide and thiotepa, with methotrexate
      being the most effective. We believe that both cell lines: RK-33 and RK-45 could
      be a suitable model for studying larynx cancer biology, however, further
      characterization of their properties is needed.

PMID- 12056643
TI  - Preliminary evaluation of mast cells and angiogenesis processes in experimental
      fibrosarcoma.
AB  - The aim of the study was the evaluation of angiogenesis processes in fibrosarcoma
      induced by 3-methylcholanthrene (3-Mc) in reference to the number of mast cells
      (MCs). 76 male Wistar rats were divided into 4 groups: two experimental (E)
      groups--after injection of 0.2 mg 3-Mc dissolved in olive oil (0.25ml), and 2
      control (C) groups. In E1 group, 52 rats were killed after development of the
      fibrosarcoma; E(2)--10 rats were killed before development of the tumor; C(1)-8
      rats received 0.25ml olive oil; C(2)--8 rats received no treatment. Tissue
      material was fixed in buffered formalin or Carnoy's and Bouin's fluid. Paraffin
      sections were stained with H+E and Azan methods, and with alcian blue-saphranine
      and toluidine blue. Immunohistochemical reactions detecting tryptase in MCs were
      also performed. Angiogenic objects (microvessels and single endothelial cells)
      were recognized using antibodies against factor VIII (vWF), P selectin (CD-62P),
      and CD-90. We found a distinct relationship between intensification of
      neoangiogenesis at the tumor periphery and increased number of MCs.

PMID- 12056644
TI  - Immunocytochemical evaluation of metallothionein (MT) expression in myoepithelial
      cells of ductal mammary carcinoma and its relation to survival time: analysis of
      7-year course of the disease.
AB  - Myoepithelial cells participate in the development of mammary glands and have
      been suggested to play a role in the biology of mammary cancer. Recent studies
      demonstrated in the cells expression and overexpression of metallothionein (MT):
      a low molecular weight, cystein-rich protein which participates, i.a., in the
      multidrug resistance to cvtostatic drugs. The present study was aimed at
      examining the relation between results of immunocytochemical (ICC) detection of
      MT expression in myoepithelial cells, present in structures of a ductal mammary
      carcinoma, and survival of the patients. In sections originating from 43 patients
      with ductal mammary carcinoma ICC reactions were performed to detect MT and to
      confirm the presence of myoepithelial cells (using antibodies to smooth muscle
      actin). Survival of the patients was also determined in the course of 7-year
      observations. Statistical analysis using the Coxe's model did not detect
      relations between MT expression intensity, in the myoepithelium on one hand and
      patient survival on the other (chi2=0.003 p=0.96).

PMID- 12056645
TI  - Proliferative activity of papillary carcinoma and benign papillary hyperplasia of
      thyroid follicular cells.
AB  - Papillary structures of follicular cells are observed in nodular goiter, cysts,
      hyperplastic areas of follicular tumors, Graves' disease, thyroiditis and
      carcinomas. The distinction of papillary carcinomas from benign lesions has
      important implication for clinical management. The aim of the study was to test a
      marker of proliferation activity (MIB-1) in the diagnosis of benign and malignant
      thyroid papillary proliferation. The study was carried out in 98 women with
      papillary carcinoma, nodular goiter. intracystic proliferation. Graves' disease
      and hyperplastic areas of follicular benign tumors. The formalin fixed, paraffin
      embedded specimens were microscopically examined using HE staining and
      immunostaining with MIB-1 antibody (DAKO). The proliferative index (PI) was
      significantly higher in malignant than in benign papillary hyperplasia. Our
      results may provide additional information for differential papillary
      proliferation diagnosis by FNAB.

PMID- 12056646
TI  - P53 protein expression in oral squamous cell cancer in relation to some of its
      clinicopathological variables.
AB  - Oral squamous cell cancer develops through a multistep process by the
      accumulation of genetic and phenotypic changes. Loss of P53 tumor suppressor gene
      function represents the most common genetic lesion in human cancer. The
      significance of P53 expression for the development and progression of oral
      squamous cell cancer has still to be evaluated. The aim of this study was to
      estimate relationships between P53 protein expression and some
      clinicopathological variables of established or presumed prognostic value. A
      series of 129 oral squamous cell cancers was investgated retrospectively for
      expression of P53 protein by immunohistochemistry of paraffin-embedded tissue
      sections. The slides were stained with H+E and by immunohistochemistry with anti
      human P53 antibody. Positive immunohistochemical staining for P53 protein was
      present in 75 (58%) oral cancer cases. There were no statistically significant
      correlations between oral cancer P53 expression and tumor site, grading, mitotic
      index, invasive margin type, as well as patients age and sex. Our results suggest
      that immunohistochemical overexpression of P53 is an important markerof
      accomplished neoplastic transformation in oral cavity lesions but it does not
      play a crucial role in the tumor progression.

PMID- 12056647
TI  - Prognostic significance of CD34 expression in early cervical squamous cell
      carcinoma.
AB  - The aim of the study was to evaluate angiogenesis as an independent prognostic
      factor and to determine the correlation of the microvessel density (MD) with
      lymph node metastases and survival rate in 73 women operated because of invasive
      squamous cell carcinoma (SCC) of the uterine cervix at clinical stages lb and IIa
      (FIGO). The patients were divided into two groups: I--25 (34.4%) with survival
      rate <5 years and II--48 (65.6%) with survival rate >5 years. Angiogenesis was
      quantified in light microscope using an assay for CD34. The CD34 antibody
      intensely immunostained single endothelial cells as well as larger microvessels.
      In the study. differences were revealed by comparing the MD between both groups.
      The 5-year overall survival rate for patients with high MD was significantly
      worse than for those with low MD (p<0.003). A correlation was found between
      angiogenesis intensity and vascular involvement as well as the incidence of lymph
      node metastases. Thus, tissue expression of CD34 in SCC appears to be a
      significant prognostic indicator.

PMID- 12056648
TI  - Immunohistochemical studies in diagnosis of the uncommon cases of tumours of the
      central nervous system.
AB  - There is a growing evidence that tumoursof the central nervous system (CNS)
      exhibit some immunophenotypic aberrations pointing to the multipotential cell
      differentiation. However, the immunohistochemistry remains still very helpful in
      differential diagnosis and nosologic classification of the CNS neoplasms. The
      purpose of this paper is to present the immunomorphological pattern of some rare
      neoplasms of neuroepithelial origin that over last years were recognised and
      classified as new clinico-pathological entities. Histological and
      immuniohistochemical features of three cases including pleomorphic
      xanthoastrocytoma, chordoid glioma and central neurocytoma are reported with
      special references to immunohistochemical differentiation of these neoplasmswith
      other tumours of similar morphology but different histogenesis.

PMID- 12056649
TI  - PTHrP and cytokeratins in human epidermis.
AB  - We have demonstrated the presence of parathyroid hormone-related peptide (PTHrP)
      in cells of human epidermis, employing immunocytochemical techniques. Cells of
      human epidermal layers demonstrated variable intensity of the reaction. The least
      pronounced reaction was detected in cells of the basal and the most pronounced
      reaction in cells of the granular layer. Ultrastructural studies demonstrated
      that gold particles labeled bundles of keratin filaments. Therefore, at the
      subsequent stage of the studies we examined the type of filaments to which PTHrP
      was bound, using immunocytochemical reactions with antibodies against
      cytokeratins 10, 14, 16 and 19. Positive reaction was obtained for cytokeratins
      10, 14 and 16. The reaction pattern obtained for cytokeratins 10 and 16 most
      closely resembled that of PTHrP. Double labeling with colloidal gold was
      performed at the ultrastructural level. The results obtained in this way
      demonstrated that PTHrP most probably binds to filaments built of cytokeratin 16.
      By binding to the cytokeratin, PTHrP may possibly affect growth and
      differentiation of keratinocytes.

PMID- 12056650
TI  - The assessment of post mortem structural changes in the human epidermis.
AB  - The structure of epidermis and appearance of keratinocytes is described in intact
      skin specimens from human corpses stored after death under refrigeration. Two
      groups of alterations can be identified depending on the epidermal layer. In the
      spinous layer, the cells are characterized by crescent-shaped nuclei surrounded
      by a hollow area. The number of such cells increases significantly each day
      during the first 8 days post mortem (dpm), and their frequencies follow
      respective regression equations, so as to enable the post mortem time estimation
      with one day accuracy. In the basal layer, distorted, balloon-shaped cells with
      pycnotic nuclei appear, which with the lapse of time are forming groups, and
      eventually the epidermis in those places separates from the dermis. The presence
      of both described changes seems to indicate whether the skin sample was obtained
      from the living organism or after the death.

PMID- 12056651
TI  - Histochemical and biochemical studies on the secretory mechanisms of some glands
      of guinea-pigs treated with histamine.
AB  - The experiments were carried out on 60 mature male guinea-pigs, randomly
      allocated into six groups. Animals from Group I (control) received intracardiac
      injections of 0.25 cm3 0.9% NaCl, while animals from all other groups received
      intracardiac injections of histamine after the intraperitoneal application of H1,
      H2 and muscarinic receptor blockers. The thyroids. adrenals, parotid glands and
      pancreas were collected. The levels of cAMP in the homogenates of all these
      glands, adrenaline in the adrenal glands, thyroxine and triiodthyronine in the
      thyroid glands and alpha-amylase in the pancreas and in the parotid glands were
      studied. Moreover, histological stainings and histochemical reactions were done
      for colloid in the thyroid glands, for adrenaline in the adrenals and for zymogen
      in the parotid glands and pancreas. The results suggest that histamine causes non
      selective. H1-dependent secretion of thyroxine and triiodthyronine. selective, H1
      dependent secretion of adrenaline and selective, H2-dependent secretion of alpha
      amylase, without the participation of muscarinic receptors.

PMID- 12056652
TI  - The ultrastructure of the peritoneal membrane in chronically dialysed rats with
      spontaneous peritonitis: preliminary observations.
AB  - In this paper we describe ultrastructure of the peritoneal membrane from single
      peritoneal biopsies collected from chronically dialysed rats with spontaneous
      peritonitis. The results were compared with those obtained in chronically
      dialysed animals without peritonitis. In rats with peritonitis, peritoneum was
      much thicker than in peritonitis-free animals. The increased thickness of the
      peritoneum during peritonitis was due to infiltration of the submesothelial
      tissue with oedematous fluid and to the presence of huge amount of cells in the
      stroma. The connective tissue cells were accumulated just underneath the
      peritoneal surface. In deeper parts of the interstitium, infiltrating acute
      inflammatory cells were present (lymphocytes, polymorphonuclear cells:
      neutrophils and eosinophils). Inversely, the increased thickness of the
      peritoneum in peritonitis-free animals was mainly due to enhanced amounts of
      collagen. Additionally, in rats with peritonitis, the surface was often denuded
      of mesothelial cells. The damaged mesothelial cells that detached from the
      peritoneal surface were also found. In conclusion, the morphological changes
      observed in rats with peritonitis are similar to those reported in humans, thus
      the model of peritonitis in dialysed rats can be used for the study of peritoneal
      remodeling during peritoneal dialysis complicated by peritonitis.

PMID- 12056653
TI  - The effect of prolonged ischaemia and cryopreservation on the cell viability of
      human aortic and femoral artery allografts.
AB  - The viability of the human arterial allograft cells depends on the time and
      method of vessel procurement and storage. In this study, an evaluation of the
      effect of the duration of 4 degrees C ischaemia and cryopreservation on human
      aortic and femoral artery allograft viability was performed. After the isolation
      of arterial wall cells, the identification of cultured cells was performed using
      mRNA analysis for estimation of smooth-muscle markers of differentiation: desmin
      and heavy-caldesmon. The viability of cells from the medial layer of the aortic
      wall ranged from 74 to 90% (61-79% for femoral arteries). Cold ischaemia time
      (from harvesting until the beginning of the preparation) is a statistically
      significant factor influencing smooth muscle cell viability. Smooth muscle cells
      represented the majority of live cell population.

PMID- 12056654
TI  - Hematopoiesis in snakes (Ophidia).
AB  - Locations of the hematopoietic tissue have been described in the following
      ophidian species: Bothrops jararaca, Bothrops jararacusu, Waglerophis merremii,
      Elaphe teniura teniura, Boa constrictor, and Python reticulatus. Studies were
      carried out on perfusion fixed vertebrae, ribs, spleen, liver, thymus, and
      kidney. Routine histological technique was applied using both light and electron
      microscopy. Hematopoietic tissue was found in the following locations of the
      vertebrae: neural spine, neural arch, postzygophysis processes, hypapophysis,
      vertebral centre. Moreover, intense hematopoiesis was found inside the ribs. In
      the spleen and thymus, only lymphopoiesis was found. Hematopoietic islets in the
      spleen were sporadically found only in young specimens. No hematopoiesis was
      observed in the liver and kidney. In the studied species, there were no
      differences in the location of hematopoietic tissue. A new model of mature and
      immature blood cell release to the lumen of marrow sinuses different from that
      known to operate in higher vertebrates is proposed.

PMID- 12056655
TI  - Cajal bodies (coiled bodies) in the nuclei of the house cricket (Acheta
      domesticus) oocytes.
AB  - The morphology and fine structure of Cajal bodies (coiled bodies, CB) in the
      germinal vesicles (oocyte nuclei) of the house cricket, Acheta domesticus have
      been analyzed. It is shown that in the studied species CBs arise as early as in
      the youngest previtellogenic oocytes, and are located next to or within
      aggregations of multiple nucleoli. Surprisingly, two morphological types of CBs
      have been found in the analyzed specimens. On the basis of EM studies we suggest
      that they represent subsequent developmental stages of CB morphogenesis.

PMID- 12056656
TI  - Distribution of cytoskeletal elements in the ovarioles of Mutilla sp. (Insecta,
      Hymenoptera).
AB  - The ovaries of Mutilla sp., as those of other hymenopterans, consist of meroistic
      polytrophic ovarioles. Within each ovariole, a terminal filament, a germarium,
      and a vitellarium can be distinguished. The germaria contain numerous dividing
      and/or differentiating groups (clusters) of germ cells. The vitellaria are
      composed of several, linearly arranged, ovarian follicles; each follicle consists
      of an oocyte and a group of nurse cells. Distribution of cytoskeletal elements
      (microfilaments and microtubules) throughout the ovarioles of Mutilla sp. has
      been studied on whole mount preparations stained with rhodamine-conjugated
      phalloidin and FITC-labelled anti-tubulin.

PMID- 12056658
TI  - Cytoarchitecture of the ovarioles in scale insects (Hemiptera, Coccinea).
AB  - Telotrophic ovarioles of scale insects are subdivided into tropharia (=trophic
      chambers) and vitellaria that contain single developing oocytes. Tropharium
      encloses trophocytes (=nurse cells) and arrested oocytes. The central area of the
      tropharium, termed the trophic core, is devoid of cells. Both trophocytes and
      oocytes are connected to the trophic core: trophocytes by cytoplasmic processes,
      oocytes by means of nutritive cords. The trophic core, processes and nutritive
      cords are filled with bundles of microtubules. The trophocytes contain large
      lobated nuclei with giant nucleoli. Fluorescent labelling with DAPI has shown
      that trophocyte nuclei are characterized by high contents of DNA. In the cortical
      cytoplasm of trophocytes, numerous microfilaments are present. The developing
      oocyte is surrounded by a simple follicular epithelium. The cortical cytoplasm of
      follicular cells contains numerous microtubules and microfilaments.

PMID- 12056657
TI  - The ovaries of Cicadomorpha: distribution of microfilaments and microtubules in
      terminal filament cells.
AB  - The ovaries of the investigated homopterans are telotrophicmeroistic and consist
      of several (7-21 ) ovarioles. Each ovariole is composed of three elements: an
      anteriorly localized terminal filament, a tropharium, and a posterior
      vitellarium. The latter comprises several developing ovarian follicles in a
      linear arrangement. The terminal filaments are relatively solid and composed of
      two distinct types of cells: the apical cells (ApCs) and the basal cells (BaCs).
      The BaCs are disc-shaped and oriented perpendicularly to the long axis of the
      ovariole, whereas the ApCs are strongly elongated and arranged parallel to this
      axis. The distribution of cytoskeletal elements has been studied with the use of
      electron microscope and histochemical methods. We show that the ApCs house
      prominent bundles of highly ordered microfilaments and/or parallel arranged
      microtubules. In contrast, BaCs contain only individual microtubules that are
      predominantly located in peripheral regions of the cells. It is suggested that
      microfilaments and microtubules present in the ApCs are responsible for the
      mechanical rigidity of the terminal filaments.

PMID- 12056659
TI  - Calcium-cadmium competition in ovarian vitellogenic follicles of Galleria
      mellonella as revealed by X-ray microanalysis.
AB  - Dissected ovarioles of Galleria mellonella were exposed for 60 min to cadmium,
      supplied to insect culture medium in amount equalling that of calcium therein.
      The sections of ovarioles treated with a fixative precipitating both elements and
      embedded in epon were examined using energy-dispersive X-ray microanalysis
      system. Analysis of the digital maps obtained suggests a free inflow of Ca2+ and
      Cd2+, in approximately equal amounts. Calcium-cadmium competition was revealed
      within the whole sample as well as in the zoomed fragments comprising ooplasm
      filled with yolk and trophocyte nucleolus.

PMID- 12056660
TI  - Development of mucous cells in taste discs of anurans.
AB  - Differentiation of the lingual taste discs (TDs) was studied in tadpoles of Rana
      esculenta, Hyla arborea and Pelobatesfuscus by means of LM, TEM, and SEM. The
      process of differentiation of mucous cells (MCs) within a TD anlage was
      investigated subsequently from 39th to 46th Gosner's developmental stage. In R.
      esculenta and P. fuscus, the MCs are distinguishable in TD anlages not earlier
      than at the 42nd tadpole Gosner's stage. At that stage TDs anlages are covered by
      a single layer of ordinary epithelial cells. Starting from the stage 44, tips of
      TDs progressively open outside and free surfaces of MCs can be distinguished as
      an area with numerous microfolds. At developmental stages 45 and 46, numerous
      electron-dense secretory granules can be seen in the supranuclear cytoplasm of
      MCs. The presence of mucopolysaccharides in H. arborea and P. fuscus was observed
      from the 44th-45th tadpole developmental stage.

PMID- 12056661
TI  - Cytochemical studies on histone-type and protamine-type proteins during
      spermiogenesis in Chara vulgaris and Chara tomentosa.
AB  - Comparative studies concerning detection of histone-type and protamine-type
      proteins were carried out on Chara species (C. vulgaris, C. tomentosa). Analysis
      of antheridia during spermiogenesis (stages I-X) of both Charta species showed
      very similar staining patterns obtained after reactions revealing the examined
      proteins. Cytochemical studies showed a replacement of lysine-rich histone
      proteins by more basic arginine-rich ones during medium spermiogenesis (st. VI
      VIII) in two Charta species, while late spermiogenesis (st. IX) and mature
      spermatozoids (st. X) were characterised by the presence of protamine-like
      proteins only.

PMID- 12056662
TI  - Expression of mRNA for cytokines (TNF-alpha and IL-1alpha) in human
      cytomegalovirus (HCMV) and hepatitis B virus (HBV) infections.
AB  - The study was aimed at detecting cellular sources of transcripts for two
      cytokines, TNF-alpha and IL-1alpha in infection with human cytomegalovirus (HCMV)
      or hepatitis B virus (HBV). The studies were performed on paraffin sections of
      organs (liver, pancreas, spleen, lungs) obtained upon autopsy from a child
      deceased due to acute inborn HCMV infection, on paraffin sections of liver
      biopsy, obtained from a child with HCMV-induced chronic hepatitis, and of liver
      biopsies obtained from children with chronic type B hepatitis (n = 13). The
      classical in situ hybridization was applied with digoxygenin-labeled probes and
      amplification by the ImmunoMax technique. In HCMV infection, the most pronounced
      expression of mRNA for TNF-alpha and Il-1alpha was detected in pancreatic islets
      (mainly in beta cells) and, then, in a decreasing sequence, in liver (in
      macrophages and sinusoidal endothelial cells) and in lungs (in alveolar
      macrophages). No expression of the two cytokines was detected in the spleen. In
      HBV infection, weak expression of TNF-alpha and more intense expression of IL
      1alpha in the liver were observed, mainly in sinusoidal endothelial cells and in
      macrophages as well as in hepatocytes. These results were confirmed by
      immunocytochemical experiments.

PMID- 12056663
TI  - Ontogeny of the expression of some catecholamine synthesising enzymes in the
      female porcine preoptic area.
AB  - Ontogeny of the catecholaminergic system of the preoptic area (PA) was studied in
      various animal species including mice, rats, cats and lower vertebrates. Until
      now, there has been no data about development of catecholaminergic structures in
      the porcine PA. To study this problem, hypothalami from six groups of animals
      were collected. Three groups of foetuses (70, 84 and 112 days old) and three
      groups of female pigs (1 day, 10 weeks and 7-8 months old) were used. Nerve
      structures immunoreactive for the studied substances: tyrosine hydroxylase (TH),
      dopamine beta-hydroxylase (DbetaH) and phenylethanoloamine-N-metylthransferase
      (PNMT) were observed in different periods. In PA, TH-IR (immunoreactive)
      structures appeared before 70th day of foetal life, DbetaH-IR between 70th and
      84th day of foetal live and PNMT-IR only in 10-week old and adult animals. In the
      PA of 70-day old foetuses, single smooth and varicose nerve fibres immunoreactive
      only to TH were found. In PA of 84-day old foetuses, additionally, single nerve
      cell bodies immunoreactive to TH were shown and some of them also contained
      immunoreactivity to DbetaH. In PA of 1-day old piglets, moderate numbers of nerve
      fibres immunoreactive to TH and only single TH/DbetaH-IR nerve terminals were
      observed. TH-IR nerve cell bodies were also moderate in number and many of them
      contained simultaneously immunoreactivity to DbetaH. In PA of 10-week old pigs, a
      moderate number of immunopositive nerve fibres was observed. They contained
      mainly TH, but part of them stained also for TH/DbetaH. Only very few nerve
      fibres containing exclusively DbetaH were found. These nerve terminals were
      observed in a close vicinity of blood vessels. In PA, moderate numbers of TH-IR
      nerve cell bodies were found, some of them contained also immunoreactivity to DH
      but never to PNMT. Perikarya containing PNMT were TH-negative. In the PA of
      sexually mature sows, additional, single, large nerve cell bodies (about 35
      microm in a diameter) containing TH only were found. In many cases, TH- and
      DbetaH-IR "basket-like" structures surrounding nerve cell bodies were seen,
      suggesting an influence of those fibres on the neuronal activity.

PMID- 12056664
TI  - Formation and structure of nutritive cords in telotrophic ovarioles of snake
      flies (Insecta: Raphidioptera).
AB  - Telotrophic ovariole of Raphidia spp. is composed of the anteriorly located
      terminal filament, tube-shaped tropharium, the vitellarium and the ovariole
      stalk. The tropharium consists of a central syncytial core surrounded by one cell
      thick layer of tapetum cells. Early previtellogenic oocytes differentiate at the
      base of tropharium. Both the oocytes and the tapetum cells are connected with the
      central syncytium by delicate intercellular bridges. At the onset of
      previtellogenic growth, the anterior parts of the oocytes become extended and
      form long cytoplasmic projections--nutritive cords. Each nutritive cord contains
      numerous microtubules that show no preferential orientation within the cord but
      diminishing anterior-posterior gradient of distribution. Irregular arrangement of
      microtubules indicates that this cytoskeletal scaffold does not play any role in
      directed transport within the ovariole but instead constitutes one of the
      elements of the structural framework of the nutritive cord. Besides microtubules,
      the stability of the nutritive cords in Raphidia ovarioles is maintained by the
      rim-shaped membrane foldings lined with microfilaments.

PMID- 12056665
TI  - Further ultrastructural research of Chara vulgaris spermiogenesis: endoplasmic
      reticulum, structure of chromatin, 3H-lysine and 3H-arginine incorporation.
AB  - On the basis of morphological features, 10 consecutive structural phases of
      spermatids were identified in Chara vulgaris spermiogenesis. They were
      schematically presented. In early and middle spermiogenesis, i.e. during the
      period preceding formation of fibrillar structure of mature spermatozoid nucleus,
      a slight remodelling of chromatin, accompanied by proplastid transformation into
      an amyloplast as well as by development of 2 flagella and a microtubular
      manchette, is observed. First, condensed chromatin concentrates around the
      nuclear envelope (phases III-V) and then it transforms into a network-like
      structure (phase VI). This change in chromatin structure is preceded by nucleolar
      extrusion to the cytoplasm where nucleoli become degraded (phase IV) and by a
      dynamic development of rough endoplasmic reticulum (RER) (phase V) which is
      continuous with the nuclear envelope and with RER of the adjacent spermatids via
      plasmodesmata. The inner membrane of the nuclear envelope invaginates into the
      nucleoplasm in which "nuclear reticulum" appears. It all happens during increased
      3H-arginine and 3H-lysine incorporation into proteins which are rapidly
      translocated into the nucleus. In medium-late spermiogenesis (phases VI-VIII),
      network-like condensed chromatin disappears. Next, the structure of the nucleus
      changes dramatically. Short, randomly positioned fibrils (phase VII) appear and
      gradually become longer (phase VIII), thicker (phase IX) and more distinct, lying
      parallel to the surface of elongating and curling nucleus. Membranes of the
      nuclear envelope become closer to each other and a distinct dark layer--probably
      lamin--appears adhering to the inner membrane of the nuclear envelope. Towards
      the end of spermiogenesis (phase X), very densely packed parallel helices, ca 2
      nm in diameter, are visible. The surfaces of flagella and the spermatozoid are
      covered with diamond-shaped larger and smaller scales, respectively. Helically
      coiled spermatozoids are liberated from antheridial filament cells through
      earlier created (phase VIII) "liberation pores" with pads of unknown nature.

PMID- 12056667
TI  - Comparison of echocardiographic changes after short- and long-duration
      spaceflight.
AB  - BACKGROUND: Previous echocardiographic studies of astronauts before and after
      short-duration (4-17 d) missions have demonstrated a decrease in resting left
      ventricular stroke volume, but maintained ejection fraction (EF) and cardiac
      output. Similar studies before and after long-duration (129-144 d) spaceflight
      have been rare and their overall results equivocal. METHODS: Echocardiographic
      measurements (M-mode, 2-D, and Doppler) were obtained from short-duration (n =
      13) and long-duration (n = 4) crewmembers to evaluate cardiac chamber sizes and
      function. RESULTS: Compared with short-duration astronauts, long-duration
      crewmembers had decreases in EF (+6+/-0.02 vs. -10.5+/-0.03%, p = 0.005) and
      percent fractional shortening (+7+/-0.03 vs. -11+/-0.07%, p = 0.015), and an
      increase in left ventricular end systolic volume (-12+/-0.06 vs. +39+/-0.24%, p =
      0.011). CONCLUSIONS: These data suggest a reduction in cardiac function that
      relates to mission duration. As the changes in BP and circulating blood volume
      are reported to be similar after short- and long-duration flights, the smaller EF
      after longer spaceflights may be due to a decrease in cardiac function rather
      than altered blood volume.

PMID- 12056666
TI  - The effect of repeated altitude exposures on the incidence of decompression
      sickness.
AB  - INTRODUCTION: Repeated altitude exposures in a single day occur during special
      operations parachute training, hypobaric chamber training, unpressurized flight,
      and extravehicular space activity. Inconsistent and contradictory information
      exists regarding the risk of decompression sickness (DCS) during such hypobaric
      exposures. HYPOTHESIS: We hypothesized that four short exposures to altitude with
      and without ground intervals would result in a lower incidence of DCS than a
      single exposure of equal duration. METHODS: The 32 subjects were exposed to 3
      different hypobaric exposures--condition A: 2 h continuous exposure (control);
      condition B: four 30-min exposures with descent/ascent but no ground interval
      between the exposures; condition C: four 30-min exposures with descent/ascent and
      60 min of ground interval breathing air between exposures. All exposures were to
      25,000 ft with 100% oxygen breathing. Subjects were observed for symptoms of DCS,
      and precordial monitoring of venous gas emboli (VGE) was accomplished with a
      SONOS 1000 echo-imaging system. RESULTS: DCS occurred in 19 subjects during A
      (mean onset 70+/-29 min), 7 subjects in B (60+/-34 min), and 2 subjects in C
      (40+/-18 min). There was a significant difference in DCS incidence between B and
      A (p = 0.0015) and C and A (p = 0.0002), but no significant difference between B
      and C. There were 28 cases of VGE in A (mean onset 30+/-23 min), 21 in B (41+/-35
      min), and 21 in C (41+/-32 min) with a significant onset curve difference between
      B and A and between C and A, but not between B and C. Exposure A resulted in four
      cases of serious respiratory/neurological symptoms, while B had one and C had
      none. All symptoms resolved during recompression to ground level. CONCLUSION:
      Data indicate that repeated simulated altitude exposures to 25,000 ft
      significantly reduce DCS and VGE incidence compared with a single continuous
      altitude exposure.

PMID- 12056668
TI  - Effect of frequency and direction of horizontal oscillation on motion sickness.
AB  - BACKGROUND: Low frequency horizontal oscillation can cause motion sickness in
      some transportation systems, but the influence of the frequency, magnitude,
      direction, and duration of oscillation are poorly understood. HYPOTHESIS: It was
      hypothesized that motion sickness was independent of the direction of horizontal
      oscillation (fore-and-aft or lateral) and that there was no difference in the
      motion sickness produced by different frequencies of horizontal oscillation
      (between 0.2 and 0.8 Hz) when subjects were exposed to the same peak velocity of
      motion at each frequency. METHOD: The 192 subjects were exposed within a closed
      cabin to sinusoidal oscillation with a velocity of +/- 0.50 ms(-1). Each subject
      experienced up to 30 min of motion while sitting with eyes open on a seat with a
      low backrest. The 16 conditions involved either fore-and-aft or lateral
      oscillation at 8 different frequencies: (i) 0.20 Hz, (ii) 0.25 Hz, (iii) 0.315
      Hz, (iv) 0.40 Hz, (v) 0.50 Hz, (vi) 0.63 Hz, (vii) 0.80 Hz, or (viii) a
      stationary control condition. Subjects provided ratings of their motion sickness
      symptoms at 1-min intervals during the 30-min exposures. RESULTS: Each frequency
      of oscillation produced significantly more sickness than the static control
      conditions. Overall, there were no significant differences in the sickness
      produced by the seven different frequencies or between the sickness produced by
      fore-and-aft or lateral oscillation. Self-ratings of motion sickness
      susceptibility provided by subjects before participating in the experiment were
      positively correlated with their illness ratings during the experiment.
      CONCLUSIONS: With horizontal oscillation over the range 0.2 to 0.8 Hz, motion
      sickness is very approximately dependent on the peak velocity of oscillation. An
      acceleration frequency weighting having a gain inversely proportional to
      frequency would provide a convenient simple method of evaluating this type of
      motion in transport. However, the results suggest that a more complex weighting,
      reflecting decreased nauseogenicity at higher and lower frequencies would be more
      accurate. The direction of motion (i.e., fore-and-aft or lateral) had no effect
      on the sickness experienced.

PMID- 12056669
TI  - Pituitary-adrenal and pituitary-thyroid hormone responses during exercise-cold
      exposure after 7 days of exhaustive exercise.
AB  - BACKGROUND: After several days of exhaustive exercise in mild-warm environments,
      cutaneous vasoconstrictor responses to cold exposure are less effective in
      conserving body heat than in the rested condition. Hypothalamic-pituitary-adrenal
      and hypothalamic-pituitary-thyroid axes hormones could mediate this response
      since they may affect vasoconstriction. The effects of exertional fatigue on
      pituitary-adrenal hormones and thyroid hormone responses to exercise-cold stress
      are unknown. HYPOTHESIS: We hypothesized that 7 consecutive days of exercise
      would decrease adrenocorticotropin (ACTH) and cortisol, while elevating thyroid
      stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) and that
      these hormones would be related to a blunted vasoconstrictor response to cold.
      METHODS: Nine male volunteers walked, completely wetted, for up to 6 h in 5
      degrees C air, when rested (day 0, control) and after 7 consecutive days (day 7)
      of exhaustive exercise (4 h each day of mixed aerobic and anaerobic activities in
      thermoneutral conditions). Blood was sampled on day 0 and day 7 at baseline (0700
      hours), and before and immediately after cold exposure. RESULTS: At 0700 hours,
      ACTH and cortisol were elevated (p < 0.05) after 7 d of exercise, compared with
      control conditions. Following exercise-cold exposure, cortisol, T3, and T4
      increased (p < 0.05) similarly on both day 0 and day 7. ACTH and TSH did not
      increase as a result of exercise-cold exposure on either day. CONCLUSIONS: These
      data indicate that 7 d of exercise elevates basal (0700 hours) pituitary-adrenal
      stress hormones (ACTH, cortisol). However, 7 d of exercise did not modify adrenal
      or thyroid hormone responses, relative to the day 0 cold exposure, suggesting
      that they are not responsible for the blunted vasoconstriction during exercise
      cold exposure following 7 consecutive days of exercise.

PMID- 12056670
TI  - Fiber size, type, and myosin heavy chain content in rhesus hindlimb muscles after
      2 weeks at 2 G.
AB  - BACKGROUND: Fiber atrophy and an increase in the percentage of fast fibers have
      been observed in Rhesus leg muscles after spaceflight. HYPOTHESIS: Hypergravity
      will result in muscle fiber hypertrophy and an increase in the percentage of slow
      fibers. METHODS: Open muscle biopsies were obtained from Rhesus soleus, medial
      gastrocnemius (MG), and tibialis anterior (TA) muscles before and after 14 d of
      centrifugation (2 G) and in time-matched controls. Cage activity levels were
      measured by telemetry. RESULTS: Based on monoclonal antibody binding for myosin
      heavy chains (MHC), the fastest region of soleus contained a higher proportion of
      type I+II (27 vs. 13%) and had a tendency for a lower proportion of type I (38
      vs. 61%, p = 0.10) fibers after than before centrifugation. There was a higher
      proportion of type I+II fibers in post- vs. pre-2 G (10 vs. 0.6%) MG biopsies.
      Fiber type distribution and MHC composition were unaffected in the TA. Overall,
      mean fiber sizes were unaffected by centrifugation. Average cage activity levels
      were 36% lower during than before 2 G. CONCLUSIONS: Our hypothesis was rejected.
      The changes in the proportion of fibers expressing type I MHC are the reverse of
      that expected with chronic loading of extensors and, paradoxically, are similar
      to changes observed with chronic unloading, such as occurs during spaceflight, in
      this primate model. The data are consistent with the observed decrease in total
      daily activity levels.

PMID- 12056671
TI  - Prediction of electrical impedance parameters for the simulated leg segment of an
      aircraft pilot under G-stress.
AB  - BACKGROUND: Blood accumulation in the lower extremities of fighter pilots has
      been known to induce loss of peripheral vision and consciousness. G suits and
      anti-G straining maneuvers applied to lower limbs do not work according to the
      actual status of blood accumulation. Therefore, the problem of blood accumulation
      in the legs requires further investigation. METHOD: The leg segment of an
      aircraft pilot has been modeled as a cylinder containing its anatomical structure
      of skin-fat layer, muscles, bones, and blood volume in the form of inner
      cylinders. Finite element analysis (FEA) was applied to the leg model with
      suitable boundary conditions. Predicted leg-segment electrical impedance (LEI)
      without blood accumulation has been compared with the measured experimental value
      using electrical impedance plethysmography (EIP). The effects of 7% blood pooling
      were analyzed by electrical impedance of the leg segment and its constituents by
      increasing the diameter of blood volume cylinder. RESULTS: The LEI has been
      predicted to be 46.7 omega, which corresponds well with experimental value of
      46.0 omega and predicted value, being 1.58% higher. Predicted LEI was reduced to
      44.2 omega during simulation of blood accumulation in FE model. The relative
      contributions of admittance for leg constituents fat, muscle, bones and blood
      volume are also found to be 2.96, 75.58, 0.33, and 11.13%, respectively.
      CONCLUSION: A computer simulation technique has been developed to predict
      electrical impedance parameters of the leg segment and its constituents with and
      without blood pooling. These results will be useful in further research and
      clinical applications for aircraft pilots under acceleration (G) stress.

PMID- 12056673
TI  - Central effects of cinnarizine: restricted use in aircrew.
AB  - HYPOTHESIS: Our aim was to establish the effects of cinnarizine, a drug used for
      the treatment of motion sickness, on daytime sleepiness and performance. METHODS:
      The effects of cinnarizine (15, 30, and 45 mg) were assessed on digit symbol
      substitution, tracking, vigilance, and on subjective and objective (daytime sleep
      latencies) sleepiness in six healthy volunteers between the ages of 20 and 34 yr
      (mean 27 yr) from 1.0 h prior to ingestion to 8.0 h after ingestion. The study
      was placebo-controlled and double-blind in a six-way, cross-over design.
      Promethazine (10 mg) was used as an active control. RESULTS: No effects of 15 mg
      cinnarizine were observed on performance. Sleep latencies were reduced at 3.5 and
      5.0 h after ingestion, and the subjects as a group reported increased sleepiness
      at 5.0 and 6.5 h after ingestion. With 30 mg cinnarizine there was evidence of
      impaired performance at 5.0, 6.5, and 8.0 h after ingestion. Sleep latencies were
      not reduced, but the subjects as a group reported increased sleepiness 5.0 h
      after ingestion. With 45 mg cinnarizine there was evidence of impaired
      performance 5.0 h after ingestion. Sleep latencies were reduced at 5.0 and 6.5 h
      after ingestion, and the subjects as a group reported increased sleepiness 6.5 h
      after ingestion. Promethazine (10 mg) shortened sleep latencies from 2.5 to 5.0 h
      after ingestion, and the subjects as a group reported increased sleepiness
      overthis period. CONCLUSION: Cinnarizine is not free of central activity over the
      usual therapeutic dose range of 15 to 30 mg. It is contraindicated for motion
      sickness in aircrew involved in the control of aircraft. Caution should be
      exercised in the use of the drug by other aircrew who may be involved in tasks
      which demand continued attention.

PMID- 12056672
TI  - Vascular leukocyte sequestration in decompression sickness and prophylactic
      hyperbaric oxygen therapy in rats.
AB  - BACKGROUND: Evidence for a causal relationship between decompression sickness
      (DCS) and leukocyte sequestration was assessed in a rat model based on the
      effects of interventions which impede cell-to-cell adherence, including
      hyperbaric oxygen therapy (HBO2). HYPOTHESIS: We hypothesized that leukocyte
      adhesion to vessels may play a role in DCS. METHODS: Rats were subjected to
      decompression stress and their ability to ambulate on a rotating drum was
      assessed to quantify functional neurological deficits. Leukocyte adherence in the
      brain was measured by a myeloperoxidase (MPO) radioimmunoassay. Interventions
      included infusion of antibodies to render rats neutropenic or to inhibit
      leukocyte beta2 integrin adhesion molecules. Tissue gas bubbles were imaged and
      quantified using a transmission ultrasound camera. RESULTS: Decompressed rats
      manifested a deficit in their ability to ambulate and a five-fold elevation in
      concentration of MPO in brain. Neutropenic rats, and those infused with antibody
      fragments to inhibit leukocyte beta2 integrins, did not exhibit brain MPO
      elevations, nor a deficit in ambulatory function. HBO2 was used in a prophylactic
      manner to address its ability to inhibit leukocyte beta2 integrin-mediated
      adherence without reducing the presence of decompression-induced bubbles.
      Prophylactic HBO2 prevented cerebral leukocyte sequestration and the performance
      deficit. CONCLUSIONS: The results implicate beta2 integrin-mediated leukocyte
      adhesion in neurological deterioration after decompression stress, and offer new
      insight into the therapeutic action of HBO2. Immunomodulatory approaches,
      including prophylactic HBO2, may improve the safety of decompression procedures
      in undersea and space exploration.

PMID- 12056674
TI  - Assessment of personality and crew interaction skills in successful naval
      aviators.
AB  - PURPOSE: We were interested in studying a full range of successful aviators to
      discern which personality factors were present and whether these factors
      correlate with age, rank, and accumulated flight time. METHOD: The Armstrong
      Laboratory Aviator Personality Survey (ALAPS) was administered to 312 designated
      naval aviators and flight officers from a variety of aircraft communities. The
      sample included O-3/O-4 elite aviators who were selected for their squadron
      billets based on superior performance, O-5/O-6 aviators selected for command
      positions, and 59 flag officers. RESULTS: The junior aviators scored higher on
      the factor associated with Dogmatism and lower on the factor associated with Team
      Orientation and Socialness. This pattern was reversed for the flag officers,
      while O-5/O-6 aviators received intermediate scores on each of these factors.
      CONCLUSIONS: The present study demonstrates a correlation between specific ALAPS
      factors and experience, rank, age, and flight time. The combination of high
      Dogmatism, low Team Orientation, and low Socialness in junior aviators could
      suggest lower openness to crew input and increased risk for mishaps.

PMID- 12056675
TI  - An evaluation of in-flight medical care in the U.S.
AB  - BACKGROUND: In-flight medical care has been studied for many years. In an effort
      to evaluate in-flight medical care delivery on U.S. airlines, this study includes
      a detailed correlation between in-flight medical care, patient response, and
      postflight follow-up. METHODS: A survey of five U.S. domestic air carriers from
      October 1, 1996 to September 30, 1997 showed 1132 in-flight medical incidents.
      These airlines accounted for approximately 22% of scheduled U.S. domestic
      enplanements during the period. RESULTS: Results indicate that there was good
      overall agreement between in-flight and postflight diagnoses (79% of cases), and
      passenger condition improved in a majority of cases (60%). CONCLUSIONS: The
      results suggest that in-flight diagnoses were generally accurate and treatment
      appropriate.

PMID- 12056677
TI  - Incidence of symptomatic thrombosis in a stable population of 650,000: travel and
      other risk factors.
AB  - Despite recent intensive media interest, the incidence of traveler's thrombosis
      is unknown. We have undertaken a study of all symptomatic cases of venous
      thrombosis, presenting to a hospital, in a fixed population of 650,000. There
      were 1,250 cases of venous thromboembolism diagnosed over a 2-yr period. Of
      these, only 47 (3.8%) answered positively to the question" did you make a journey
      of more than 100 mi in the 4 wk prior to diagnosis?" Among the travelers, 60% had
      traveled by air, 36% by road, and the remainder by rail. At least one medical
      risk factor for venous thrombosis was present in all but three of our cohort. We
      conclude that, taking into consideration the enormous number of passengers who
      travel, the relative risk of traveler's thrombosis is likely to be low. The
      incidence of this complication in the North East of England is 1 per 27,660 of
      the whole population.

PMID- 12056676
TI  - Aircraft accidents and other causes of death among Norwegian commercial pilots.
AB  - BACKGROUND: When entering the profession, pilots need to be in better health than
      the general population. During their careers they are under close medical
      supervision, which could influence their life-long mortality. METHODS: The cohort
      was established from the files of the Norwegian Civil Aviation Administration and
      included people who had valid licenses as commercial pilots between 1946 and
      1994. Basic data about their flight careers were recorded. The cohort was linked
      to the Cause of Death Registry. The observed number of deaths was compared with
      those expected, based on national rates. RESULTS: A group of 3707 male pilots was
      followed over 70,832 person-years. There were 342 deaths vs. 362.8 expected, with
      a standardized mortality ratio (SMR) of 0.94, and a 95% confidence interval (95%
      CI) of 0.85-1.05. Aircraft accidents with 97 deaths had a major influence on
      total mortality and the SMR for all other causes was 0.68 (95% CI 0.59-0.77). The
      SMR for cancer was 0.89 (95% CI 0.71-1.11) and for circulatory diseases 0.53 (95%
      CI 0.42-0.67). The highest SMR for total mortality in pilots < 30 yr old was 3.52
      (95% CI 2.54-4.76). For this age group 38 of a total of 42 deaths were caused by
      aircraft accidents. It was indicated that almost half the deaths of aircraft
      accidents took place in private aircraft. CONCLUSIONS: Due to aircraft accidents
      young pilots have a higher mortality rate than the general population; other
      harmful effects on the mortality of pilots in their workplace were not found. At
      all ages pilots have a better life expectancy than the general population.

PMID- 12056678
TI  - Effect of muscle tensing on cerebral oxygen status during sustained high +Gz.
AB  - BACKGROUND: Successful monitoring of oxyhemoglobin during +Gz exposure was
      recently achieved using near-infrared spectroscopy (NIRS). To assess the effects
      of muscle tensing on sustained +Gz tolerance, we measured muscle activity and
      cerebral oxygen status (COS) during anti-G straining maneuvers at sustained high
      +Gz. METHOD: We exposed 21 male pilots wearing CSU-13/P anti-G suit to two
      different centrifuge profiles: 1) short-term repeated exposure (5 to 20 s) at 4,
      5, 6, 5.5, or 7 Gz; 2) sustained exposure to a + 7Gz plateau for 30 s. During the
      Gz exposures, surface electromyographic (EMG) measurements were taken from the
      vastus medialis (VM) and rectus abdominis (RA) muscles. At the same time, the COS
      was recorded from the left forehead area using a commercial NIRS system. Mean
      muscular tensing for each muscle was calculated as a percentage of maximal
      voluntary contraction (% MVC). RESULTS: Oxyhemoglobin (O2Hb) and total hemoglobin
      (sum of O2Hb and deoxyhemoglobin) were decreased during both short-term and
      sustained +Gz exposure. RA muscle tensing was positively correlated with changes
      in the concentration of O2Hb during sustained + 7Gz exposure (r = 0.540, p <
      0.05). RA tensing ranged from 6.2 to 36.8%MVC, and O2Hb ranged from -41.3 to 
      7.28 micromol x L(-1) during the exposures. No significant correlation was
      observed between VM tensing and O2Hb. CONCLUSION: NIRS measurements confirmed
      that a muscle straining maneuver increases G tolerance. Higher RA muscle tensing
      helps preserve brain blood volume during sustained high +Gz.

PMID- 12056679
TI  - Digital radiography in space.
AB  - With the permanent habitation of the International Space Station, the planning of
      longer duration exploration missions, and the possibility of space tourism, it is
      likely that digital radiography will be needed in the future to support medical
      care in space. Ultrasound is currently the medical imaging modality of choice for
      spaceflight. Digital radiography in space is limited because of prohibitive
      launch costs (in the region of $20,000/kg) that severely restrict the volume,
      weight, and power requirements of medical care hardware. Technological increases
      in radiography, a predicted ten-fold decrease in future launch costs, and an
      increasing clinical need for definitive medical care in space will drive efforts
      to expand the ability to provide medical care in space including diagnostic
      imaging. Normal physiological responses to microgravity, in conjunction with the
      high-risk environment of spaceflight, increase the risk of injury and could imply
      an extended recovery period for common injuries. The advantages of gravity on
      Earth, such as the stabilization of patients undergoing radiography and the
      drainage of fluids, which provide radiographic contrast, are unavailable in
      space. This creates significant difficulties in patient immobilization and
      radiographic positioning. Gravity-dependent radiological signs, such as
      lipohemarthrosis in knee and shoulder trauma, air or fluid levels in
      pneumoperitoneum, pleural effusion, or bowel obstruction, and the apical pleural
      edge in pneumothorax become unavailable. Impaired healing processes such as
      delayed callus formation following fracture will have implications on imaging,
      and recovery time lines are unknown. The confined nature of spacecraft and the
      economic impossibility of launching lead-based personal protective equipment
      present significant challenges to crew radiation safety. A modified, free
      floating radiographic C-arm device equipped with a digital detector and utilizing
      teleradiology support is proposed as a theoretical solution to help overcome many
      of these difficulties.

PMID- 12056680
TI  - Lessons learned from Shuttle/Mir: psychosocial countermeasures.
AB  - BACKGROUND: During future long-duration space missions, countermeasures need to
      be developed to deal with psychosocial issues that might impact negatively on
      crewmember performance and well-being. METHODS: In our recently completed NASA
      funded study of 5 U.S. astronauts, 8 Russian cosmonauts, and 42 U.S. and 16
      Russian mission control personnel who participated in the Shuttle/Mir program, we
      evaluated a number of important psychosocial issues such as group tension,
      cohesion, leadership role, and the displacement of negative emotions from
      crewmembers to people in mission control and from mission control personnel to
      management. RESULTS: Based on our findings, which are reviewed, a number of
      psychosocial countermeasures are suggested to help ameliorate the negative impact
      of potential psychosocial problems during future manned space missions.
      CONCLUSIONS: Crewmembers should be selected not only to rule out psychopathology
      but also to select-in for group compatibility and facility in a common language.
      Training should include briefings and team building related to a number of
      psychosocial issues and should involve both crewmembers and mission control
      personnel. During the mission, both experts on the ground and the crewmembers
      themselves should be alert to potential interpersonal problems, including the
      displacement of negative emotions from the crew to the ground. Supportive
      activities should consist of both individual and interpersonal strategies,
      including an awareness of changing leisure time needs. Finally, attention should
      be given to postmission readjustment and to supporting the families on Earth.

PMID- 12056681
TI  - Emergency medical kit for commercial airlines: an update.
AB  - As expected, the issue of medical kits for commercial airlines continues to
      attract attention, especially in light of the recent United States regulation on
      the subject. As promised in its first recommendation in 1998, the Air Transport
      Medicine (ATM) Committee has continued to monitor medical kit usage as well as
      pharmaceutical scientific developments and wishes to propose an update to its
      1998 recommendation. Lists of contents are provided for emergency medical kits of
      two types: 1) those without defibrillator/monitor or monitor; and 2) those with
      defibrillator/monitor or monitor alone. Follow up and updates on this issue will
      be an ongoing task of the ATM Committee.

PMID- 12056682
TI  - New U.S. Army three-dimentional (3D) audio research program.

PMID- 12056683
TI  - On the origin of free-viewing perceptual asymmetries.

PMID- 12056684
TI  - Can free-viewing perceptual asymmetries be explained by scanning, pre-motor or
      attentional biases?
AB  - Judgments of relative magnitude between the left and right sides of a stimulus
      are generally weighted toward the features contained on the left side. This
      leftward perceptual bias could be the result of, (a) left-to-right scanning
      biases, (b) pre-motor activation of the right hemisphere, or (c) a left
      hemispatial attentional bias. The relative merits of these explanations of
      perceptual asymmetry were investigated. In Experiment 1, English and Hebrew
      readers made luminance judgements for two left/right mirror-reversed luminance
      gradients (greyscales task). Despite different reading/scanning habits, both
      groups exhibited a leftward perceptual bias. English and Hebrew readers also
      performed a line bisection task. Scanning biases were controlled by asking
      participants to follow a marker as it moved left-to-right or right-to-left and
      then stop it as it reached the midpoint of the line. Despite controlling
      scanning, a leftward bias was observed in both groups. In Experiment 2,
      peripheral spatial cues were presented prior to the greyscales stimuli. English
      readers showed a reduction in the leftward bias for right-sided cues as compared
      to left-sided and neutral cues. Right-side cues presumably overcame a pre
      existing leftward attentional bias. In both experiments, pre-motor activation was
      controlled using bimanual responses. Despite this control, a leftward bias was
      observed throughout the study. The data support the attentional bias account of
      leftward perceptual biases over the scanning and pre-motor activation accounts.
      Whether or not unilateral hemispheric activation provides an adequate account of
      this attentional bias is discussed.

PMID- 12056685
TI  - The effect of 'masking' on picture naming.
AB  - It is frequently assumed that because compared to nonliving things, living things
      are less familiar, have lower name frequency, and are more visually complex, this
      makes them more difficult to name by patients and normal subjects. This has also
      been implicitly accepted as an explanation for the greater incidence of living
      thing disorders. Patient studies do not, however, typically contain any premorbid
      data and so, we do not know that the same variables would have necessarily
      predicted their 'normal' performance. To examine this issue, we measured picture
      naming latencies in normal subjects presented with unmasked and masked versions
      of the same line drawings. In accord with other recent studies, living things
      were named faster than nonliving things. Furthermore, contrary to some theories
      of category naming, the living thing advantage persisted regardless of whether
      stimuli were undegraded, degraded or the density of degradation. Finally,
      multiple simultaneous regression analyses showed that one visual variable
      (Euclidean Overlap) and one linguistic variable (Age of Acquisition) predicted
      naming latencies across all masked and unmasked conditions. Other variables
      either had no predictive value (Contour Overlap; Name Frequency; Category);
      predicted only high masking (Visual Complexity; Familiarity), or normal and low
      masking (Number of Phonemes). These findings imply that the more commonly
      documented deficits for living things do not reflect an exaggeration of the
      normal profile (be it with masked or unmasked stimuli) or the influence of the
      same variables that affect normal naming.

PMID- 12056686
TI  - The simon effect in schizophrenic patients with negative symptoms.
AB  - Automatic shifting of visual attention was investigated using the Simon task in
      schizophrenic patients with prevailing negative symptomatology. Reaction times
      were recorded in condition of spatial correspondence and non-correspondence
      between side of spatially defined responses and side of stimulus presentation.
      Schizophrenic patients showed asymmetries between the two hemifields attributable
      to a slowing down of reaction times for non-corresponding trials in the left
      hemifield. These results are interpreted as a deficit in the process that
      inhibits the automatic corresponding response, and in general as a difficulty to
      inhibit dependence on external stimuli, in the left hemifield/right hemisphere.

PMID- 12056687
TI  - Contribution of recollection and familiarity judgements to rate of forgetting in
      organic amnesia.
AB  - The present study sought to determine whether the rate of forgetting in amnesic
      and control participants varied as the relative contribution of familiarity
      judgements (or implicit memory) was manipulated. In Experiment 1, rates of
      forgetting were measured in two recognition conditions in which the relative
      contribution of familiarity judgements and recollection had been manipulated. No
      significant group by condition or group by condition by delay effects were found.
      In Experiment 2, we compared word recognition and word recall tasks on the
      assumption that this would produce a larger difference in the role of familiarity
      judgements versus recollection. In this case, we did obtain a significant
      difference in forgetting rates, the amnesic patients forgetting faster than the
      healthy subjects in the recall condition. In summary, amnesic patients showed
      faster forgetting on recall than recognition, which we have attributed to the
      absence of the opportunity for familiarity judgments in recall testing. We
      concluded that amnesic patients show a primary deficit in the acquisition of new
      information (with associated or secondary retrieval deficits), and that, in
      addition, they show a deficit in long-term retention detectable only on recall
      ('high recollection') testing.

PMID- 12056689
TI  - Callosal function in multiple sclerosis: bimanual motor coordination.
AB  - Evidence of callosal dysfunction in patients with multiple sclerosis (MS) was
      examined using a test of bimanual coordination. MS patients were slower than non
      patients on the Bimanual Coordination Test (BCT) on both unimanual trials (simple
      motor speed) and bimanual trials (intermanual coordination). Further, when
      compared to normals, MS patients exhibited a substantially greater difference
      between bimanual and unimanual response time, suggesting a deficit in
      interhemispheric motor interactions. A subgroup of MS subjects who showed
      markedly inefficient callosal transmission had previously been identified on the
      basis of abnormal evoked potentials (low amplitude cross-callosal evoked
      potentials). In comparisons of MS subgroups, the deficit in bimanual motor
      coordination was found only in MS patients with EP evidence of inefficient
      callosal transmission. These data support the conclusion that deficits in
      bimanual motor coordination occur in MS and that these deficits are related to
      callosal dysfunction.

PMID- 12056688
TI  - Crowding effects on word identification in developmental dyslexia.
AB  - The effect of crowding on the identification of words was examined in normal
      readers and subjects with developmental dyslexia. In Experiment 1, a matching
      task was used. Words were presented either alone or embedded in other words.
      Vocal reaction times (RT) of dyslexics were slower and more sensitive to the
      presence of the surrounding stimuli than those of control subjects. Similar
      results were obtained in a control experiment using the same task for strings of
      symbols (isolated or crowded) instead of words. These data indicate that
      differences in crowding in control and dyslexic subjects arise at a pre
      linguistic level. In Experiment 2, vocal RTs to word reading were measured. Two
      conditions putatively reducing the effect of crowding were tested: increasing
      inter-letter spacing and blurring. A moderate increase of inter-letter spacing
      produced faster vocal RTs in dyslexics, while no effect was present in normal
      controls. Moderate blurring of stimuli did not change dyslexics' RTs, while
      normal readers became slower. Group and individual results are discussed to
      evaluate the extent to which crowding contributes to the genesis of developmental
      dyslexia.

PMID- 12056690
TI  - Story processing in patients with damage to the prefrontal cortex.
AB  - The prefrontal cortex is known to be involved in performing complex cognitive
      tasks requiring reasoning, planning and decision-making. Neuropsychological
      evidence also supports the idea that the prefrontal cortex is generally involved
      in encoding and retrieving complex events, such as action and narrative
      knowledge. Patients with frontal lobe damage are reported to have difficulty in
      processing different aspects of narrative representations, such as the figurative
      moral meaning, syntactic features, and inference generation. In the present
      study, we examined story processing in 17 patients with frontal lobe lesions and
      compared their performance to 7 amnesic patients and 17 normal controls. Two
      stories were presented by using two slightly different processing demands in
      order to assess the subject's ability to draw inferences on-line during the
      course of comprehension or later retrieval. Although all patients had impaired
      story memory, patients with frontal lobe lesions showed a pattern of deficit at
      an early stage of story comprehension that specifically involved the ability to
      reconstruct the sequential links among events and to extract inferential
      knowledge from the text during encoding. Amnesic patients were severely impaired
      in recalling story semantic units, including single events and larger narrative
      constituents, as well as in the event recognition task. Consequently, they were
      unable to establish inferential relations among the events and, thus, the global
      sequential structure of the stories during retrieval. In contrast, they had no
      difficulty in extracting inferential knowledge during story comprehension on the
      basis of readily available information. This study shows that damage to different
      cortical regions may induce impairments at various levels of story processing.

PMID- 12056691
TI  - Aware and unaware perception in hemispatial neglect: evidence from a stem
      completion priming task.
AB  - The current study used the process dissociation procedure in conjunction with a
      stem-completion priming task to disentangle the influences of aware and unaware
      perception in patients with hemispatial neglect. One lateralized picture prime
      was presented simultaneously with a filler picture followed by a centrally
      presented word stem. In the inclusion condition participants were asked to
      complete the word stem with the previously presented picture name; in the
      exclusion task they were asked to complete the stem with the name of a picture
      other than the one previously presented. Findings indicated that neglect patients
      had reduced unaware perception of pictures presented in the left visual field and
      an absence of awareness for those same pictures. In addition, patients had
      reduced awareness for right visual field pictures, but unaware perception
      remained intact. These findings suggest that observations of preserved
      information processing in neglect are due to residual unaware perception and not
      due to residual awareness of information in the neglected hemispace.

PMID- 12056692
TI  - Why is magical ideation related to leftward deviation on an implicit line
      bisection task?
AB  - Right hemispatial inattention is a neurocognitive deficit observed in thought
      disordered schizophrenia patients, persons with schizotypal personality disorder
      and healthy participants with high scores on schizotypy scales. We administered a
      schizotypy inventory, the Magical Ideation (MI) scale, to forty healthy, right
      handed men who had copied and later recalled the Rey-Osterrieth complex figure.
      Implicit line bisection performances were defined as the bisecting lines of the
      complex figure's large rectangle and were recorded for the copy and delay
      conditions. MI scores were significantly correlated with a leftward shift in
      bisections in the delay but not copy condition, indicating a significant
      relationship between the degree of right hemispatial inattention and number of
      magical beliefs in healthy participants. We describe a model in which these
      beliefs are conceptualized as a consequence of a hemispheric imbalance,
      specifically, of a "right hemisphere processing bias". This model accounts for
      (1) the leftward shifts in spatial attention and (2) the language deficits
      associated with psychosis and related symptom clusters which have hitherto been
      addressed in separate literatures. Clinically, the Rey-Osterrieth test may
      provide a means to assess implicit hemispatial inattention in psychotic patients.

PMID- 12056693
TI  - Spatial awareness: a function of the posterior parietal lobe?

PMID- 12056694
TI  - Where does the free online scholarship movement stand today?

PMID- 12056695
TI  - Stay out of the hospital! Wherever you are in the world.

PMID- 12056696
TI  - About failures in medical systems (continued).

PMID- 12056697
TI  - Profiling: "Editorial on 'Survival after progression in patients with follicular
      lymphoma: analysis of prognostic factors'", by S. Montoto et al. (Ann Oncol 2002;
      13: 523-30).

PMID- 12056698
TI  - Inhibition of bcl-2 as cancer therapy.

PMID- 12056699
TI  - Frequency and risk factors of anthracycline-induced clinical heart failure in
      children: a systematic review.
AB  - BACKGROUND: Anthracyclines are essential for the treatment of the children with
      cancer. We performed a systematic review to evaluate the existing evidence of the
      frequency and risk factors of anthracycline-induced clinical heart failure (A
      CHF) in children. DESIGN: Medline was searched for articles reporting the
      frequency of A-CHF, published from 1966 to December 2000. Information about study
      features, risk factors and frequency were abstracted, and a validity score was
      given for each study. The potential predictive factors of A-CHF were analysed
      both within and across the studies. RESULTS: The frequency of A-CHF in children
      was estimated in 30 studies described in 25 articles. All studies have serious
      methodological limitations. The frequency varied between 0% and 16%. In the
      analysis across the studies the type of anthracyclines and the maximal dose in 1
      week explain a considerable part of the variation of the frequency of A-CHF.
      CONCLUSIONS: Doxorubicin and a dose above 45 mg/m2 within 1 week seemed to
      increase the frequency of A-CHF. Well designed and executed studies are needed to
      accurately estimate the frequency of A-CHF and reliably assess the importance of
      potential risk factors.

PMID- 12056700
TI  - Raltitrexed: current clinical status and future directions.
AB  - Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to
      5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer
      (CRC), and has single-agent activity in a variety of advanced solid tumours.
      Although both raltitrexed and 5-FU are thymidylate synthase inhibitors,
      raltitrexed has a specific mode of action and a toxicity profile distinct from 5
      FU. The mechanism of action of raltitrexed is also completely different from that
      of oxaliplatin, irinotecan and other drugs with which it has been combined. These
      properties, together with preclinical data, suggested that combinations of
      raltitrexed with 5-FU, other chemotherapeutic agents, or radiotherapy could
      result in improved therapies for a variety of advanced solid tumours, including
      advanced CRC. This review outlines the appropriate management of patients treated
      with raltitrexed, whether as monotherapy or in combination, and discusses the
      preliminary results of combination studies with raltitrexed in a range of tumour
      types including advanced CRC, malignant mesothelioma, gastric, pancreatic, head
      and neck, and non-small-cell lung cancers. Of particular interest is the
      combination of raltitrexed and oxaliplatin, which has shown promising antitumour
      effects in first-line treatment of advanced CRC and malignant mesothelioma, a
      disease that is refractory to chemotherapy.

PMID- 12056701
TI  - Survival after progression in patients with follicular lymphoma: analysis of
      prognostic factors.
AB  - BACKGROUND: The purpose of this study was to identify prognostic parameters for
      patients with follicular lymphoma (FL) in first progression/relapse. These would
      be useful for selection of high-risk patients for inclusion in trials aimed at
      determining the effect of new treatment approaches in such patients. PATIENTS AND
      METHODS: Ninety patients (48 male, 42 female, median age 56 years) diagnosed with
      FL, in a single institution during a 20 year period and relapsing/progressing
      after an initial response to therapy, were recruited. The main end-point of the
      study was survival from progression (SFP). Univariate and multivariate analyses
      were performed, including among the predictive variables the response duration
      (RD) after the initial treatment and the main features of the patients at the
      first progression or relapse. RESULTS: Five-year SFP was 47% (95% confidence
      interval 35% to 58%). Patients with RD following initial therapy >2 years had a
      longer SFP (5-year SFP 63 versus 33%, P = 0.012). Other variables with prognostic
      interest for SFP were stage at diagnosis and the following variables at relapse:
      age, bulky disease, performance status, serum lactate dehydrogenase level, serum
      beta2-microglobulin level, bone marrow involvement, stage and International
      Prognostic Index rating. In the multivariate analysis, poor performance status at
      progression and a RD <2 years were the most important unfavorable variables to
      predict SFP. CONCLUSION: In patients with FL, RD along with performance status at
      progression are features that predict SFP. These variables could thus be useful
      to select candidates for experimental treatments.

PMID- 12056702
TI  - Relevance of intraocular involvement in the management of primary central nervous
      system lymphomas.
AB  - BACKGROUND: Reported data regarding intraocular lymphoma (IOL) management are
      anecdotal. Cases of IOL included in an international multicentre series of 378
      immunocompetent patients with primary central nervous system lymphomas (PCNSLs)
      were reviewed. PATIENTS AND METHODS: Staging included slit-lamp examination in
      170 patients: IOL was diagnosed in 22 cases (13%). A concomitant brain lesion was
      detected in 21 cases. Planned treatment was chemotherapy followed by radiotherapy
      in 13 cases, chemotherapy alone in three and radiotherapy, followed by or not by
      chemotherapy in five; one patient was not treated. Chemotherapy included high
      dose methotrexate in 12 cases. Ten patients received intrathecal chemotherapy.
      Radiotherapy consisted of whole brain irradiation, followed by or not by a tumour
      bed boost; ocular irradiation was planned in 15 cases. Irradiation in one patient
      without brain lesions was limited to the orbits only (50 Gy). RESULTS: IOL was
      positively correlated to systemic symptoms and meningeal disease. Fifteen
      patients (71%) achieved an objective response; 16 patients experienced a failure
      (2-year failure-free survival 34+/-10%). Failures involved the eyes in eight
      cases, with a 2-year time to ocular relapse of 59+/-11%. Ocular failure was less
      common in patients treated with chemotherapy plus ocular irradiation and was
      associated with a significantly shorter survival. Seven patients are alive
      [median follow-up 53 months, 2-year overall survival (OS): 39+/-11%] , five of
      whom were treated with ocular irradiation. The patient with isolated IOL is alive
      and disease-free at 14 months. OS of the entire series was similar to that of
      PCNSL patients with negative slit-lamp examination. CONCLUSIONS: IOL is usually
      associated with concomitant brain disease and shows a survival similar to that of
      the rest of PCNSLs. Chemotherapy combined with ocular irradiation resulted in
      better control of ocular disease, which seems to be associated with survival. In
      view of the potential role of ocular irradiation, the use of chemotherapy alone
      in phase II trials should be critically reconsidered in PCNSL patients with
      ocular disease.

PMID- 12056703
TI  - A pilot trial of G3139, a bcl-2 antisense oligonucleotide, and paclitaxel in
      patients with chemorefractory small-cell lung cancer.
AB  - BACKGROUND: Chemorefractory small-cell lung cancer (SCLC) is defined as disease
      that progresses during primary therapy or within 3 months of completion of
      primary therapy. Patients with chemorefractory SCLC have a very poor prognosis,
      and no treatment has been shown to be of significant clinical benefit. Elevated
      expression of Bcl-2 is found in the majority of SCLCs and has been associated
      with therapeutic resistance. Suppression of Bcl-2 levels through the use of
      G3139, an antisense oligonucleotide complementary to the mRNA encoding Bcl-2,
      might increase the antitumor efficacy of cytotoxic therapy. PATIENTS AND METHODS:
      Twelve patients with chemorefractory SCLC participated in this pilot trial of
      paclitaxel combined with G3139. G3139 was given by continuous i.v. infusion over
      7 days at a fixed dose of 3 mg/kg/day. Paclitaxel dose was initially 175 mg/m2 on
      day 6, but was decreased to 150 mg/m2 due to myelosuppression observed in two of
      the three patients treated in the first dose cohort. RESULTS: The combination of
      paclitaxel at 150 mg/m2 and G3139 at 3 mg/kg/day was found to be feasible and
      well tolerated. No objective responses were observed, but two patients had stable
      disease, one remaining stable on therapy for >30 weeks. Plasma G3139 levels were
      determined, and were found to be highest in the patient with prolonged stable
      disease, suggesting that individual variation in metabolism and clearance of the
      antisense oligonucleotide may influence activity. CONCLUSIONS: This study
      demonstrates that G3139 can be combined with paclitaxel in a cytotoxic dose
      range, and suggests that a similar combination be tested for activity in the
      context of chemoresponsive disease.

PMID- 12056704
TI  - Phase I, dose-finding study of capecitabine in combination with docetaxel and
      epirubicin as first-line chemotherapy for advanced breast cancer.
AB  - PURPOSE: Capecitabine is an oral fluoropyrimidine with considerable activity and
      minimal myelosuppression and alopecia. This phase I study evaluated the addition
      of capecitabine to epirubicin/docetaxel combination therapy as first-line
      treatment for advanced breast cancer. PATIENTS AND METHODS: Twenty-three female
      patients with advanced breast cancer received capecitabine (765-1060 mg/m2 twice
      daily on days 1-14 of a 3-week treatment cycle) in combination with epirubicin
      and docetaxel (75 mg/m2 i.v. on day 1). RESULTS: The maximum tolerated dose of
      capecitabine was 985 mg/m2 and the principal dose-limiting toxicity was febrile
      neutropenia. No grade 3/4 anemia or thrombocytopenia occurred. There were no
      grade 4 non-hematological events and grade 3 events other than alopecia were
      rare. Alopecia occurred in all patients and treatment cycles, and asthenia
      occurred in all patients and in 84% of treatment cycles. Other frequent adverse
      events included nausea, vomiting, fever, paresthesia and elevated transaminase
      levels. An objective response to treatment was observed in 91% (95% confidence
      interval 72% to 99%) of patients. CONCLUSIONS: The addition of capecitabine to
      docetaxel/epirubicin combination therapy provides a well-tolerated and active
      first-line chemotherapy regimen in patients with advanced breast cancer, and
      merits phase II/III evaluation.

PMID- 12056705
TI  - Gemcitabine and oxaliplatin for patients with advanced or metastatic pancreatic
      cancer: a North Central Cancer Treatment Group (NCCTG) phase I study.
AB  - BACKGROUND: The study was performed to determine the maximum tolerated dose (MTD)
      of gemcitabine and oxaliplatin in patients with advanced or metastatic pancreatic
      adenocarcinoma (ACA). PATIENTS AND METHODS: Pancreatic ACA patients, with
      previously untreated advanced or metastatic disease, were enrolled in a dose
      escalation study of gemcitabine and oxaliplatin. Oxaliplatin was given
      intravenously on day 1 and gemcitabine intravenously on days 1 and 8 of a 3-week
      cycle. Doses of both drugs were increased with sequential cohorts of patients
      until dose-limiting toxicity (DLT) was observed. RESULTS: A total of 18 patients
      were enrolled to three dose levels. DLT of neutropenia and a severe infection was
      noted at a dose of gemcitabine 1250 mg/m2 and oxaliplatin 130 mg/m2.
      Hematological toxicity and nausea and vomiting were the most common grade 3/4
      toxicities. The MTD, gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2, was well
      tolerated. Three confirmed responses were seen. CONCLUSIONS: The MTD of
      gemcitabine and oxaliplatin in patients with pancreatic ACA was determined. A
      phase II study of this combination is ongoing and will be reported separately at
      a later date.

PMID- 12056706
TI  - Capecitabine (Xeloda) in combination with oxaliplatin: a phase I, dose-escalation
      study in patients with advanced or metastatic solid tumors.
AB  - OBJECTIVES: This phase I, dose-escalation study was conducted to determine the
      recommended dose of intermittent oral capecitabine in combination with a fixed
      dose of i.v. oxaliplatin. Secondary objectives included evaluation of the safety
      profile and antitumor activity. PATIENTS AND METHODS: Twenty-three patients with
      advanced or metastatic solid tumors received a 21-day regimen of oral
      capecitabine (500, 825, 1000 or 1250 mg/m2 twice daily, days 1-14) in combination
      with oxaliplatin (130 mg/m2, 2-h i.v. infusion, day 1). Dose-limiting toxicities
      were determined during the first treatment cycle, and safety and efficacy were
      evaluated throughout treatment. RESULTS: The recommended dosing schedule is oral
      capecitabine 1000 mg/m2 twice daily (days 1-14) with i.v. oxaliplatin 130 mg/m2
      (day 1) in a 21-day treatment cycle. The principal dose-limiting toxicity was
      diarrhea. The most frequent treatment-related adverse events occurring during the
      study were gastrointestinal (nausea/vomiting, diarrhea) and neurological
      (dysesthesia, paresthesia). The majority of treatment-related adverse events were
      mild to moderate in intensity, and no grade 4 adverse events occurred in the 15
      patients treated at or below the recommended dose. The most common grade 3/4
      laboratory abnormalities were lymphocytopenia (52% of patients), thrombocytopenia
      (22%; grade 3 only), neutropenia (17%) and hyperbilirubinemia (17%). Among
      patients treated at or below the recommended dose level (n = 15), only two
      patients experienced grade 3 neutropenia and no patients experienced grade 4
      neutropenia. Partial tumor responses occurred in six patients (26%), including
      five of nine patients (55%) with colorectal cancer. All responding patients were
      pretreated with 5-fluorouracil and four responders had received prior irinotecan.
      CONCLUSIONS: Oral capecitabine with i.v. oxaliplatin is a feasible combination
      regimen that shows promising antitumor activity in patients with colorectal
      cancer. There is an ongoing, phase II study to further characterize the safety
      and efficacy of this combination as first-line therapy for metastatic colorectal
      cancer, using the recommended dose identified in this study.

PMID- 12056707
TI  - First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable
      safety profile compared with intravenous 5-fluorouracil/leucovorin.
AB  - PURPOSE: To evaluate the safety profile of capecitabine using data from a large,
      well-characterized population of patients with metastatic colorectal cancer
      treated in two phase II studies. In these trials, capecitabine achieved
      significantly superior response rates, equivalent time to disease progression and
      equivalent survival compared with 5-fluorouracil (5-FU)/leucovorin. PATIENTS AND
      METHODS: Patients (n = 1207) were randomized to either oral capecitabine (1250
      mg/m2 twice daily, on days 1-14 every 21 days) or intravenous (i.v.) bolus 5
      FU/leucovorin (Mayo Clinic regimen). RESULTS: Capecitabine demonstrated a safety
      profile superior to that of 5-FU/leucovorin, with a significantly lower incidence
      of diarrhea, stomatitis, nausea, alopecia and grade 3 or 4 neutropenia leading to
      significantly fewer neutropenic fever/sepsis cases and fewer hospitalizations.
      All patients in the capecitabine group received a starting dose of 1250 mg/m2
      twice daily and the majority (66%) did not require dose modification for adverse
      events. In the 5-FU/leucovorin group, 58% of patients did not require dose
      reduction for toxicities. The capecitabine dose-modification scheme reduced the
      recurrence of key toxicities without compromising efficacy. In both treatment
      arms, patients with moderate renal impairment at baseline (estimated creatinine
      clearance 30-50 ml/min) experienced a higher incidence of grade 3 or 4
      toxicities. This increase was more pronounced with 5-FU/leucovorin. CONCLUSIONS:
      Capecitabine is at least as effective, better tolerated and more convenient than
      i.v. 5-FU/leucovorin as treatment for patients with metastatic colorectal cancer.
      Analysis of data from two large phase III trials demonstrates that efficacy is
      not compromised in patients requiring a dose reduction for adverse events. The
      phase III data and an additional pharmacokinetic study support a lower starting
      dose in patients with moderate renal impairment at baseline (calculated
      creatinine clearance 30-50 ml/min) and a contra-indication in patients with
      severely impaired creatinine clearance at baseline (<30 ml/min). For patients
      with normal or mildly impaired renal function at baseline, the standard starting
      dose is well tolerated. The incidence and severity of adverse events in patients
      with moderate renal impairment at baseline who were treated with 5-FU/leucovorin
      was more pronounced, indicating that capecitabine provides a better-tolerated
      alternative.

PMID- 12056708
TI  - Oral eniluracil/5-fluorouracil in patients with inoperable hepatocellular
      carcinoma.
AB  - BACKGROUND: Conventional systemic chemotherapy currently available for patients
      with inoperable hepatocellular carcinoma is ineffective. The purpose of this
      study was to evaluate the safety and efficacy of eniluracil/5-fluorouracil (5-FU)
      in the treatment of patients with this highly refractory disease. PATIENTS AND
      METHODS: This multicenter, open-label study evaluated a 28-day oral regimen of 5
      FU (1 mg/m2 twice daily) plus the dihydropyrimidine dehydrogenase inhibitor,
      eniluracil (10 mg/m2 twice daily), in patients with chemotherapy-naive or
      anthracycline-refractory inoperable hepatocellular carcinoma. RESULTS: A total of
      36 patients enrolled into the study. No patient showed a confirmed partial or
      complete tumor response, although nine patients (25%) had a best response of
      stable disease. The median duration of progression-free survival was 9.6 weeks
      [95% confidence interval (CI) 9.1-10.6 weeks], and the median duration of overall
      survival was 32.7 weeks (95% CI 17.4-71.6 weeks). Eniluracil/5-FU was well
      tolerated. Diarrhea, the most frequent treatment-related non-hematological
      toxicity, occurred in 11 patients (31%). Hematological toxicities were infrequent
      and usually mild. CONCLUSIONS: Eniluracil/5-FU as a 28-day oral outpatient
      regimen is well tolerated by patients with inoperable hepatocellular carcinoma,
      although minimal activity was observed when given as monotherapy at the dose used
      in this study.

PMID- 12056710
TI  - Determinants of chronic fatigue in disease-free breast cancer patients: a cross
      sectional study.
AB  - BACKGROUND: Quality of life after cancer treatment becomes more important as the
      number of long-term survivors increases. This study aimed to investigate
      complaints of fatigue after treatment for breast cancer. PATIENTS AND METHODS:
      The study patients were 150 women who had finished curative treatment for breast
      cancer by a mean of 29 months before commencement of this study. Measurements
      included computerised questionnaires and a daily Self-Observation List. RESULTS:
      Thirty-eight per cent of the sample were severely fatigued, compared with 11% in
      a matched sample of women without a history of cancer. No association was found
      between fatigue and former treatment. The 'severely fatigued disease-free breast
      cancer patient' scored more 'problematic' on psychological well-being, functional
      impairment, sleep disturbance, physical activity, social support,
      neuropsychological and social functioning compared with the 'non-severely
      fatigued disease-free breast cancer patient'. Furthermore, the severely fatigued
      patients had a lower sense of control with respect to their fatigue complaints
      and stronger breast cancer- and psychologically-related attributions with regard
      to the causes of fatigue compared with the non-severely fatigued patients.
      Regression analyses indicated that sleep disturbance, physical activity and
      causal attributions contributed significantly to the subjective experience of
      fatigue. CONCLUSIONS: Severe fatigue is a problem for almost 40% of the sample of
      breast cancer survivors. Severe fatigue is related to physical, psychological,
      social, cognitive and behavioural factors.

PMID- 12056709
TI  - Low-dose trimetrexate glucuronate and protracted 5-fluorouracil infusion in
      previously untreated patients with advanced pancreatic cancer.
AB  - BACKGROUND: 5-Fluorouracil (5-FU)-based regimens have not been shown to prolong
      survival or provide clinical benefit in patients with advanced pancreatic cancer.
      The purpose of this study was to determine the tolerability of protracted venous
      infusion (PVI) of 5-FU, modulated by a low dose of the synthetic antifolate
      trimetrexate, in patients with advanced pancreatic cancer. PATIENTS AND METHODS:
      Twenty-three chemotherapy-naive patients were evaluated. Patients were enrolled
      in four consecutive cohorts in which the weekly dose of trimetrexate was
      escalated in 10 mg/m2 increments, from 20 to 50 mg/m2. PVI 5-FU was administered
      at a fixed dose of 225 mg/m2/day. Treatment was administered for 6 successive
      weeks, every 8 weeks. RESULTS: Twenty-two patients were assessable. The maximum
      tolerated dose of trimetrexate was 40 mg/m2. The most common grade 3 and 4
      toxicity was diarrhea. There were no treatment-related deaths. Preliminary
      analysis of activity revealed a response rate of 9%, with 41% of the patients
      having stable disease for a median duration of 3.8 months. The median survival
      for the entire group was 6.9 months (range 1-29 months). A clinical benefit
      response was experienced by 27.2% of patients. CONCLUSIONS: Low-dose trimetrexate
      can be safely administered in combination with PVI 5-FU. This treatment is well
      tolerated and is associated with palliative activity in advanced pancreatic
      cancer.

PMID- 12056711
TI  - High-dose versus conventional-dose chemotherapy as first-salvage treatment in
      patients with non-seminomatous germ-cell tumors: a matched-pair analysis.
AB  - BACKGROUND: The purpose of this study was to compare high-dose chemotherapy
      (HDCT) with conventional-dose chemotherapy (CDCT) as first-salvage treatment in
      patients with relapsed or refractory non-seminomatous germ-cell tumors (NSGCT).
      PATIENTS AND METHODS: One hundred and ninety-three patients with relapsed or
      refractory NSGCT, between 1981 and 1995, were identified from two large
      databases. In 74 of these, intensification of first-salvage treatment by HDCT was
      planned. Patients were matched based on primary tumor location, response to first
      line treatment, duration of this response and serum levels of the tumor markers,
      human chorionic gonadotrophin (HCG) and alpha-fetoprotein (AFP). Multivariate
      analyses were performed using event-free survival and overall survival as primary
      endpoints. RESULTS: Full matches on all five factors were found for 38 pairs of
      patients; for a further 17 pairs, matches on at least four factors could be
      identified. Hazard ratios in favor of HDCT were obtained between 0.72 and 0.84
      [confidence interval (CI) 0.59-1.01] for event-free survival and between 0.77 and
      0.83 (CI 0.60-0.99) for overall survival, depending on the type of analysis.
      CONCLUSIONS: The current analysis suggests a benefit from HDCT, with an estimated
      absolute improvement in event-free survival of between 6 and 12% and in overall
      survival of between 9 and 11% at 2 years. This benefit is lower than expected
      from previous phase I/II studies.

PMID- 12056713
TI  - Efficacy of a chemotherapy combination for the treatment of metastatic
      neuroendocrine tumours.
AB  - OBJECTIVES: Neuroendocrine tumours (NETs) are heterogeneous neoplasms for which
      there is no standard treatment. We have previously proposed an effective
      polychemotherapy (5-fluorouracil, dacarbazine and epirubicin), which only
      produced objective responses of brief duration. The present study aimed to assess
      in a multidisciplinary manner the efficacy of the same regimen at intensified
      doses in patients with advanced NETs. PATIENTS AND METHODS: Eighty-two
      consecutive patients entered the study, of whom 21 had inoperable, locally
      advanced disease and 61 had metastatic disease. Seventy-two patients were
      evaluated for objective, biochemical and subjective responses. Response rate,
      time to progression (TTP) and overall survival (OS) were evaluated based on
      histotype. RESULTS: An objective response was observed in 20 patients (intention
      to-treat and standard analysis 24.4% and 27.8%, respectively). Complete
      biochemical and subjective responses were obtained in 25.1% and 38.9% of the
      cases. The median duration of treatment was 4 months and the objective responses
      had a median duration of 38 months. After a 60-month follow-up the median TTP and
      OS were 21 and 38 months, respectively. CONCLUSIONS: Our polychemotherapy regimen
      is effective, with long duration, and is well tolerated both for
      gastroenteropancreatic and lung NETs, as well as for tumours with a more
      aggressive clinical behaviour. The new WHO endocrine tumour histotyping,
      examining also the tumour biology, may give additional information for selecting
      patients to chemotherapy.

PMID- 12056712
TI  - A multi-institutional phase II trial of a novel inpatient schedule of continuous
      interleukin-2 with interferon alpha-2b in advanced renal cell carcinoma: major
      durable responses in a less highly selected patient population.
AB  - BACKGROUND: A prospective multi-institutional phase II trial was undertaken to
      define the activity and toxicity of a unique decrescendo infusion of interleukin
      2 (IL-2) in combination with interferon (IFN) in patients with metastatic renal
      cell carcinoma. The identical regimen has shown promise in advanced melanoma.
      PATIENTS AND METHODS: Between February 1997 and March 1999, 47 patients with
      metastatic renal cell carcinoma, from five institutions, were treated with
      outpatient s.c. IFN (10 mU/m2/day) on days 1-5, followed by inpatient IL-2 via
      continuous i.v. decrescendo infusion [18 million International Units (MIU) (I
      mg)/m2/6 h, followed by 18 MIU/m2/12 h, then 18 MIU/m2/24 h and 4.5 MIU/m2/24 h
      for the following 3 days] on days 8-12, in a hospital ward without intensive care
      unit (ICU)-type monitoring. Treatment was repeated every 4 weeks. In contrast to
      high dose IL-2 protocols, patient eligibility did not require pulmonary function
      tests and allowed serum creatinine up to 2 mg/dl. RESULTS: Among 44 eligible
      patients, 57% (25) had their primary in place, 57% (25) had bone or visceral
      involvement, and only 4% (2) had lung as their only site of disease. The overall
      response rate in 43 response-evaluable patients was 16.3% [95% confidence
      interval (CI) 5.3 to 27.3], with three complete responses and four partial
      responses observed. The median survival was 13 months; nine patients remain alive
      at >23 months. The median duration of response is 36 months (range 11.5 to 48+
      months). Toxicity was modest, consisting of typical cytokine-induced systemic
      symptoms and rare organ dysfunction. Severe grade 4 toxicity occurred in only 13%
      of the 130 cycles. CONCLUSIONS: This unique, reasonably well tolerated IL-2/IFN
      combination induced a modest response rate with a number of durable remissions.
      While the optimal IL-2-based regimen for the treatment of advanced renal cell
      carcinoma remains elusive, the present regimen should attract considerable
      interest. This is based on tumor activity very similar to high dose IL-2 in a
      patient population not as carefully selected for optimal organ function.

PMID- 12056714
TI  - Audiotapes of oncology consultations: only for the first consultation?
AB  - BACKGROUND: Patients value audiotapes of their oncology consultations and letters
      summarising the discussion, and report improved recall and satisfaction when they
      receive them. However, studies to date have provided these interventions only
      after the initial or 'bad news' consultation. This study aimed to evaluate the
      utility of audiotaping routine follow-up oncology consultations. PATIENTS AND
      METHODS: This was a prospective study following a cohort of consecutive patients
      attending routine follow-up at oncology outpatient appointments with one
      oncologist. Patients were approached when they attended their appointment and
      offered the opportunity to be audiotaped. Acceptance rates and reasons for
      refusal were documented. Two weeks after the consultation, patients were
      telephoned regarding their response to the tape and were sent a letter
      summarising the consultation. Two weeks later they received a further telephone
      call regarding the letter and their perceptions of the comparative value of the
      two interventions. RESULTS: Seventy-five per cent of patients were female and for
      40% English was not their first language. The patients had attended a median of
      14 previous oncology appointments; 52 patients were offered audiotaping, 43
      accepted and 30 decided to take home a copy of the audiotape. One patient felt
      recording had limited the discussion. Patients refused the tape most commonly
      because they felt no need for this aid, and accepted it most commonly to aid
      recall or share with family. Twenty-six patients listened to the tape, 14 did so
      more than once. Twenty had shared it with another person and over 75% thought it
      was useful. The majority (57%) preferred to receive both the tape and letter,
      with three preferring the tape alone and seven the letter. Married patients and
      those receiving bad news were more likely to want the tape. CONCLUSIONS:
      Audiotaping follow-up consultations is an inexpensive procedure that is
      appreciated by the majority of patients. Randomised controlled trials of their
      impact are warranted.

PMID- 12056715
TI  - Acute transient encephalopathy after paclitaxel infusion: report of three cases.
AB  - Paclitaxel (Taxol) is a diterpene plant product and antineoplastic agent that
      promotes the assembly of microtubules as well as stabilizing their formation by
      preventing depolymerization. Myelosuppression was found to be dose-limiting, but
      peripheral neurotoxicity is also a well known side-effect. Central nervous system
      toxicity is rare, probably because paclitaxel does not cross the blood-brain
      barrier. We observed three patients who presented with acute encephalopathy
      within 6 h after infusion of paclitaxel at normal doses. All patients had
      received prior whole brain irradiation (WBI) and one patient had prior brain
      metastasectomy. Computer tomography and magnetic resonance imaging showed no
      evidence of cerebral metastases. An effect from other organ toxicities was
      excluded in all patients. All recovered spontaneously within 4-6 h. From this we
      can conclude that paclitaxel can cause severe acute transient encephalopathy,
      which may occur more frequently after prior WBI and/or surgery due to alteration
      of small vessel function.

PMID- 12056717
TI  - Comment on "Perhaps not everyone knows that...", (Ann Oncol 2001; 12: 1186).

PMID- 12056716
TI  - The chemotherapy of metastatic gastric adenocarcinomas with hypersecretion of
      alpha-fetoprotein or beta-human chorionic gonadotrophin: report of two cases.
AB  - The chemotherapy of advanced gastric adenocarcinomas (GAs) is based on agents
      such as cisplatin, 5-fluorouracil and anthracyclins. Reproducible objective
      response rates are reported as approximately 40%. However, the median survival
      remains short, not exceeding 10 months. Amongst GA, a subset of tumours with
      increased plasma alpha-fetoprotein (alphaFP) and/or beta human chorionic
      gonadotrophin (betaHCG) levels form a well-defined histopathological entity. This
      subgroup has been associated with poor prognosis, due to the presence of poorly
      differentiated and rapidly proliferating cells. No specific chemotherapy has been
      proposed for this particular form of GA. We report two cases of patients with GA
      and hypersecretion of alphaFP and/or betaHCG. Despite bulky liver metastases and
      resistance to two standard chemotherapy regimens, both patients exhibited
      sensitivity to chemotherapy combining bleomycin, oxaliplatin and etoposide. These
      results suggest that patients with this particular subset of GA may benefit from
      chemotherapy regimens similar to those given to germ-cell tumour patients.

PMID- 12056718
TI  - Unusual presentation of Hodgkin's lymphoma.

PMID- 12056719
TI  - Human cardiac valve interstitial cells in collagen sponge: a biological three
      dimensional matrix for tissue engineering.
AB  - BACKGROUND AND AIM OF STUDY: The use of a biological, biodegradable scaffold
      remodeled by cells to resemble a valve leaflet is an attractive approach to
      tissue engineering. The study aim was to evaluate the suitability of a three
      dimensional biodegradable collagen sponge for maintenance of cell viability,
      proliferation and phenotype of cultured human cardiac valve interstitial cells
      (ICs). METHODS: Pieces of valve leaflets were snap-frozen, sectioned and stained
      by immunoperoxidase. Interstitial cells were cultured from cardiac valves and
      plated onto glass coverslips or seeded in collagen sponge, then stained by
      immunofluorescence or immunoperoxidase. A panel of antibodies was used to
      determine cell phenotype. Cell viability was assessed using a dye-based cell
      proliferation assay, and cell death by lactate dehydrogenase measurement.
      RESULTS: ICs variably expressing the phenotypic markers were found throughout the
      native valve leaflet, but particularly on the ventricular side. Cultured ICs
      either on coverslips or in collagen sponge expressed vimentin, a fibroblast
      surface antigen and variable amounts of smooth muscle (SM) alpha-actin.
      Expression of the other phenotypic markers, SM myosin, desmin and prolyl 4
      hydroxylase differed: interestingly, the ratio of cells in collagen sponge
      expressing these markers reflected that found in the native valve leaflet.
      Confocal microscopy of ICs in the collagen sponge revealed the presence of cells
      with long interconnecting extensions indicating cell communication. Cell
      proliferation and cell death assays established that cells were not only viable
      after four weeks in the sponge, but were also proliferating. CONCLUSION: This
      study demonstrates that collagen sponge is a suitable biodegradable scaffold that
      can maintain viable valve ICs and appears to enhance the capacity of the cell to
      express its original phenotype.

PMID- 12056720
TI  - Evolution of cell phenotype and extracellular matrix in tissue-engineered heart
      valves during in-vitro maturation and in-vivo remodeling.
AB  - BACKGROUND AND AIM OF THE STUDY: Contemporary tissue valves are non-viable, and
      unable to grow, repair or remodel. It was postulated that tissue-engineered heart
      valves (TEHV) fabricated from autologous cells and a biodegradable scaffold could
      yield a dynamic progression of cell phenotype and extracellular matrix (ECM), in
      vitro and in vivo, and ultimately recapitulate native valve microscopic
      architecture. METHODS: Trileaflet valve constructs were fabricated from poly-4
      hydroxybutyrate-coated polyglycolic acid seeded with ovine endothelial and
      carotid artery medial cells, cultured in vitro for 4-14 days in a pulse
      duplicator, implanted as pulmonary valves in five lambs, and explanted at 4-20
      weeks. ECM composition and collagen architecture were examined by histology
      (including Movat pentachrome stain and picrosirius red under polarized light),
      and cell phenotype by immunohistochemistry. RESULTS: Cells from in-vitro
      constructs (14 days) were activated myofibroblasts, with strong expression of
      alpha-actin (microfilaments), vimentin (intermediate filaments) and SMemb (non
      muscle myosin produced by activated mesenchymal cells). Cells from in-vivo
      explants at 16-20 weeks were fibroblast-like, with predominant vimentin
      expression and undetectable levels of alpha-actin (similar to native valve).
      Collagen elaboration and cellular expression of MMP-13 (collagenase 3) were
      evident in vitro at 14 days. In-vivo explants had increased collagen accumulation
      and strong MMP-13 expression at 4-8 weeks, but less activation (decreased
      expression of SMemb) and patchy endothelial cells at 16-20 weeks. Moreover, the
      ECM architecture of 16- to 20-week explanted TEHV resembled that of native
      valves. CONCLUSION: Cell phenotype and ECM in TEHV prepared in vitro and
      implanted in vivo are dynamic, and reflect the ability of a vital tissue to
      remodel and, potentially, to grow.

PMID- 12056721
TI  - The presence of immune stimulatory cells in fresh and cryopreserved donor aortic
      and pulmonary valve allografts.
AB  - BACKGROUND AND AIM OF THE STUDY: Heart valve allografts (HVA) used for valve
      replacement or ventricular outflow tract reconstruction may suffer from
      structural deterioration due to donor-specific immune responses. The presence of
      immune stimulatory cells, including dendritic cells and activated endothelial
      cells, has not been studied thoroughly in aortic or pulmonary HVA. The presence
      and distribution of these cells in both aortic and pulmonary HVA, before and
      after cryopreservation, was analyzed immunohistochemically. METHODS: Aortic (n =
      16) and pulmonary (n = 13) HVA, discarded for implantation due to morphological
      or technical reasons, were obtained from 12 heart-beating and nine non-heart
      beating tissue donors. Aortic and pulmonary HVA were dissected longitudinally
      into two symmetric sections by splicing of the non-coronary aortic and non-facing
      pulmonary cusps. Each symmetric half contained one-and-a-half valve cusps
      attached to the vascular wall. Fresh halves were directly fixed in formaldehyde,
      and analyzed immunohistochemically. The corresponding halves of the valves were
      decontaminated, cryopreserved, stored for at least three weeks and thereafter
      thawed according to the Heart Valve Bank protocol before analysis. RESULTS:
      Activated endothelial cells, expressing PECAM-1 (CD31), VCAM-1 and HLA class II
      molecules covered at least 50% of fresh valvular surfaces. A comprehensive
      vascular network was found in the myocardial rim and adventitial layer, which was
      covered entirely by activated endothelial cells. HLA class II-positive
      macrophages (CD68) and T lymphocytes (CD3) were found scattered in the stroma and
      subendothelial layer of the valve leaflets. Mononuclear cell clusters were found
      predominantly in relation to native degenerative foci, and more often in aortic
      valves. No difference in cellular distribution was observed between the two donor
      types. Dendritic cells positive for both S100 and CD45 were not found in immuno
      double-stained sections. Cryopreservation resulted in minor structural
      alterations in the vascular wall, and an increase of cells with pycnotic nuclei
      and reduction of adhesion molecule expression on endothelial cells. All fresh and
      cryopreserved aortic and pulmonary HVA contained abundant HLA class II-positive
      endothelial cells and sparse distribution of mononuclear cells in the luminal and
      adventitial layers. CONCLUSION: Cryopreservation minimally affected the
      extracellular matrix of HVA and diminished the cellularity of the valve graft,
      while the HLA class II expression of cells was not abrogated. Aortic valve
      allografts harbor more mononuclear cells than their pulmonary counterparts. The
      absence of dendritic cells (professional antigen-presenting cells) is compensated
      by the preservation of other cells expressing HLA class II molecules
      predominantly in the endothelium; this may be responsible for the initiation of a
      specific immune response against HVA.

PMID- 12056722
TI  - Frequencies of donor-reactive helper T lymphocytes correlate with rejection of
      aortic valve allografts in rats.
AB  - BACKGROUND AND AIMS OF THE STUDY: Human valve allografts are commonly used in
      cardiac surgery for congenital and acquired valve diseases. Particularly in the
      pediatric population, these allografts are prone to fail in the long term, and
      require replacement. In part, this failure may be due to immunological phenomena.
      The frequency of helper T lymphocytes (HTLf) measured in peripheral blood and
      spleen serves as a parameter for acute rejection in organ transplantation. The
      value of this parameter in valve transplantation was studied using the
      'Rotterdam' implantation model in rats. METHODS: HTLf were determined in
      peripheral blood and spleen at seven and 21 days after allogeneic (WAG-->DA) and
      syngeneic (DA-->DA) implantation of an aortic valved conduit. Valve competence
      was tested pre-implantation, at days 7 and 21 after implantation, and after
      explantation using a retrograde saline injection. Explanted valves were examined
      histologically. RESULTS: At seven days after allogeneic valve transplantation,
      HTLf in spleen (median 71/10(6)), but not in peripheral blood (median 26/106)
      were significantly elevated. At 21 days after allogeneic transplantation, a
      significant increase in HTLf was seen in both peripheral blood (median
      10(9)/10(6)) and spleen (median 92/10(6)). All five (100%) syngeneic grafts and
      five of seven (71%) allografts were competent at day 7. At day 21, all five
      syngeneic grafts (100%) and zero allografts (0%) remained competent (p = 0.01).
      Histologically, mononuclear cell infiltration into the allogeneic valve leaflets
      and in the vascular wall was observed at day 7. At day 21, valve leaflets
      appeared to be acellular and deformed. All syngeneic valve grafts retained normal
      morphology. CONCLUSION: After aortic valve allografting in the rat, HTLf
      correlate with valve dysfunction and histopathological signs of rejection.
      Therefore, HTLf-analysis may be a useful tool in monitoring the cellular immune
      response as an indicator for early graft dysfunction due to rejection in clinical
      valve transplantation.

PMID- 12056723
TI  - Editorial: Distribution of chordae tendinae tension in the porcine mitral valve.

PMID- 12056724
TI  - Differential tension between secondary and primary mitral chordae in an acute in
      vivo porcine model.
AB  - BACKGROUND AND AIM OF THE STUDY: Chordae tendineae may be instrumental for
      valvular-ventricular interaction, i.e. the reciprocal exchange of force between
      the left ventricular myocardium and the mitral apparatus. Chordae tendineae are
      divided into primary leading edge chordae and secondary belly chordae, and
      differences in thickness and distribution may reflect different functions of the
      two types. Primary chordae may be fundamental for leading edge control and for
      correct leaflet coaptation, while secondary chordae may act as the main mediators
      of valvular-ventricular interaction. It was postulated that tension in secondary
      chordae of the anterior leaflet is greater than in the primary chordae. The study
      aim was to investigate the distribution of chordae tendineae tension in the
      porcine mitral valve in vivo. METHODS: During extracorporeal bypass, miniature
      chordal force transducers were implanted on four chordae in 23 Danish Landrace
      pigs. Chordae tendineae tension was recorded online in the open-chest condition
      with spontaneous circulation in three different hemodynamic conditions: baseline
      with no intervention; partial aortic occlusion; and during dobutamine infusion.
      RESULTS: Systolic tension in secondary chordae under baseline conditions was
      significantly higher than in primary chordae (0.7 N versus 0.2 N, respectively).
      No significant impact on this distribution by changing the hemodynamic condition
      could be identified. CONCLUSION: Chordal tension is distributed towards the
      secondary chordae, with a tension more than three-fold that in the primary
      counterpart. The magnitude of chordal tension seems to be determined primarily by
      ventricular pressure. This finding supports the hypothesis that secondary chordae
      are more important mediators of the valvular-ventricular interaction than are
      primary chordae.

PMID- 12056726
TI  - Progression of isolated tricuspid regurgitation late after mitral valve surgery
      for rheumatic mitral valve disease.
AB  - BACKGROUND AND AIMS OF THE STUDY: Severe tricuspid regurgitation (TR) may develop
      late after mitral valve surgery without significant mitral stenosis,
      regurgitation and other causes of left heart failure. The study aim was to
      investigate severe isolated TR late after mitral valve surgery for rheumatic
      mitral valve disease. METHODS: A total of 208 patients who underwent mitral valve
      surgery (valve replacement in 121, commissurotomy in 62, valvuloplasty in 25) was
      investigated. The mean (+/-SD) follow up was 13+/-6 years. Severe isolated TR was
      defined clinically by elevated venous pressure, and echocardiographically by
      grade 4+ TR without significant mitral stenosis, regurgitation, other causes of
      left heart failure, pulmonary hypertension or rheumatic tricuspid valve. RESULTS:
      Severe isolated TR was identified in 30 patients (14%) at four to 24 years after
      mitral valve surgery. All patients had atrial fibrillation. Of these patients, 23
      had medical treatment and seven had tricuspid valve surgery. Three of the
      medically treated patients were in NYHA class IV and died from multiple organ
      failure at three to seven years after severe TR was diagnosed. Among surgically
      treated patients, four were in NYHA class IV and had postoperative complications
      (one early death, one late death), while three NYHA class II/III patients had
      very few postoperative complications. CONCLUSION: Severe isolated TR was detected
      in 14% of patients after mitral valve surgery. It is important to detect patients
      with progressive heart failure and to indicate earlier reoperation in order to
      prevent significant late mortality.

PMID- 12056725
TI  - Resolution of left atrial thrombi with anticoagulant therapy in candidates for
      percutaneous transvenous mitral commissurotomy.
AB  - BACKGROUND AND AIMS OF THE STUDY: Little is known of the fate of left atrial
      thrombus (LAT) among candidates for percutaneous transvenous mitral
      commissurotomy (PTMC) after oral anticoagulation (OA) therapy. The aim of this
      study was to estimate the resolution rate of documented LAT, and to determine its
      significant predictors among this population. METHODS: In this prospective cohort
      study all consecutive candidates for PTMC with documented LAT were followed
      between August 1996 and December 1999. All patients underwent both transthoracic
      (TTE) and transesophageal echocardiography (TEE) and received OA therapy (INR 2.0
      3.0). The fate of LAT was studied serially using both TTE and TEE. RESULTS: A
      total of 75 patients was followed for six to 34 months (mean 12.2+/-6.2 months;
      total 914 patient-months). The LAT was completely resolved in 48 patients (5.25
      per 100 pt-months; 95% CI 3.96-6.97). The overall resolution rate was 63.0 per
      100 patients per year (95% CI 47.5-83.6). Patients with resolved LAT underwent
      uneventful PTMC. The median duration of LAT resolution was 16 months (95% CI 12.7
      19.3). Significant predictors of LAT resolution were the size of the LAT (RR =
      0.8 for each 1 cm2 increase in LAT; 95% CI 0.6-0.9; p = 0.012) and severity of
      the left atrial spontaneous echo contrast (LASEC) detected by TEE (RR = 0.6 for
      each 1 level increase of the LASEC severity score; 95% CI 0.4-0.9; p = 0.032).
      CONCLUSION: The smaller the LAT and the less severe the LASEC, the greater the
      likelihood of LAT resolution after OA therapy and the enhanced possibility of
      safely performing PTMC.

PMID- 12056727
TI  - Extensive left atrial endoatriectomy for infective endocarditis.
AB  - The technique of extensive endoatriectomy of the left atrium and reconstruction
      with autologous pericardium for infective endocarditis is described. Endocardium
      of the left atrium with vegetations was completely excised from the valvular
      annulus to normal endocardium, and autologous pericardium was used to reinforce
      the endocardial defect and to allow less tension in the closure. This technique
      permits complete removal of infectious lesions and facilitates mitral valve
      replacement reinforcing the mitral annulus.

PMID- 12056728
TI  - Modified gorlin equation for the diagnosis of mixed aortic valve pathology.
AB  - BACKGROUND AND AIM OF THE STUDY: The accuracy of the Gorlin equation when applied
      to mixed valve pathology has not been investigated. An in-vitro study was
      performed to determine how a range of valve regurgitations and stenoses affects
      the Gorlin aortic valve area. METHODS: Various combinations of stenosis and
      regurgitation were simulated by placement of constricting orifices and minimal
      blockage reflux tubes within a 29-mm prosthetic pericardial valve. The orifice
      areas ranged from 0.7 cm2 to 1.75 cm2, and regurgitant fraction (RF) ranged from
      0 to 0.35. Twenty-eight tests were performed at 70 beats/min, cardiac output of 5
      l/min and systole 33-36% of the cycle. The mean pressure drops across the valve
      were adjusted to a value appropriate to blood density. Peripheral resistance was
      set to give a mean value of 1,537 dyn.s.cm(-5). RESULTS: The Gorlin area varied
      up to 0.55 cm2 from the geometric orifice area over the range of regurgitant
      fractions and stenoses. To improve the Gorlin equation, an amended mean
      volumetric forward flow rate was obtained by multiplying the cardiac output in
      the equation by the factor (1 - RF)(-1), to reconcile the equation for valvular
      regurgitation. The area predicted by the modified equation differed by <0.15 cm2
      from the non-regurgitant valve geometric orifice area over the range of
      regurgitation and stenoses simulated. CONCLUSION: The study supports the validity
      of the Gorlin equation predicting pure aortic valve stenosis (areas <1.3 cm2);
      however, the equation overestimates the severity of stenoses when regurgitation
      is present. A modified equation is proposed, which includes regurgitant fraction.
      The new equation improves the calculation of valve geometric area in the presence
      of regurgitation and may be useful in cardiac catheterization laboratories where
      mixed aortic valve pathology is being evaluated.

PMID- 12056729
TI  - Bicuspid aortic valve: abnormal aortic elastic properties.
AB  - BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is frequently
      associated with clinically relevant abnormalities of the aorta, suggesting the
      existence of a common underlying developmental defect involving the aortic valve
      and wall of the ascending aorta. The study aim was to evaluate noninvasively the
      elastic properties of the aortic root in young males with BAV, to discover
      whether structural abnormalities of the aorta might be manifested by impairment
      in elasticity. METHODS: Forty-nine young male subjects with isolated BAV were
      consecutively detected during preenrollment military screening, and studied using
      transthoracic echocardiography. Data were compared with those obtained in 45
      normal subjects, matched for gender and age. RESULTS: Patients and controls were
      comparable for body size, and systolic and diastolic blood pressures. BAVs were
      normally functioning in 18 patients (37%), and mildly regurgitant in 31 (63%).
      Measurements made by two-dimensional echocardiography showed that BAV patients
      had significantly larger aortic root dimensions at the annulus (2.4+/-0.2 versus
      2.2+/-0.2 cm, p <0.001), at the sinus of Valsalva (3.3+/-0.4 versus 2.6+/-0.3 cm,
      p <0.001), at the sinotubular junction (2.9+/-0.3 versus 2.5+/-0.2 cm, p <0.001),
      and at the proximal ascending aorta (2.8+/-0.3 versus 2.5+/-0.2 cm, p <0.001).
      Measurements made using M-mode echocardiography at 3 cm from the annulus, showed
      the difference between systolic and diastolic diameters of the aortic root to be
      significantly smaller in patients than in controls (2.1+/-1.2 versus 3.0+/-1.1
      mm, respectively, p <0.001). In patients and in controls, both aortic
      distensibility (2.7+/-1.5 versus 4.8+/-2.2 x 10(-6) cm2 dyne(-1), respectively, p
      <0.001) and aortic stiffness index (10.2+/-5.3 versus 5.03+/-1.97, respectively,
      p <0.001) were significantly different. CONCLUSION: Young male subjects with BAV
      and no or mild aortic regurgitation display large aortic size and abnormal
      elastic properties of the ascending aorta compared with controls. These findings
      confirm the notion that, in these patients, aortic root dilatation is a
      morphological correlate of intrinsic structural aortic abnormality.

PMID- 12056730
TI  - Feasibility of the ross procedure: its relationship with the bicuspid aortic
      valve.
AB  - BACKGROUND AND AIM OF THE STUDY: The feasibility of the Ross procedure, and which
      patients benefit most from its performance, have not yet been fully established.
      The study aim was to analyze the relationship between the etiology of aortic
      valve disease, the feasibility of performing the Ross procedure, and late
      pulmonary autograft performance. METHODS: Between June 1995 and June 2001, 117
      patients (77 males, 40 females; mean age 37+/-12 years) underwent the Ross
      procedure at the authors' institution. Of these patients, 53 (45.3%) had severe
      aortic stenosis, 53 (45.3%) had significant aortic insufficiency, four (3.4%) had
      active endocarditis, two (1.7%) had subaortic stenosis, and five (4.3%) had
      prosthesis dysfunction. Eighty-one patients (69%) had a bicuspid aortic valve.
      Pulmonary autograft dysfunction was defined as regurgitation grade > or =2, as
      registered by Doppler echocardiography. RESULTS: The Ross procedure was
      successful in 100 patients (85.5%); hospital mortality was 2.6% (n = 3). The
      procedure was not feasible in 17 patients (14.5%); of these, seven had bicuspid
      pulmonary valve, six had >3 mm multiple pulmonary valve fenestrations, three had
      severe pulmonary insufficiency, and one patient had dissection-related pulmonary
      valve injury. Twelve of 16 patients presenting with pulmonary valve defects had
      bicuspid aortic valve (p = 0.04). At six-year follow up, the probability of not
      requiring reoperation was 93% (confidence interval 86-100%). During follow up
      (30+/-14 months; range: 2-72 months), six patients presented with grade 2
      pulmonary autograft insufficiency, three with grade 3, and two with grade 4. Six
      of the latter 11 patients (p = 0.03) had a history of bicuspid aortic valve with
      aortic regurgitation. Freedom from autograft dysfunction was 87% (confidence
      interval 82-92%). Patients with bicuspid aortic valve and aortic valve
      regurgitation had a higher tendency towards autograft dysfunction than those with
      bicuspid aortic valve and aortic stenosis (65% versus 100%, p = 0.004).
      CONCLUSION: The feasibility of performing the Ross procedure is high, unless
      there is presence of bicuspid aortic valve. Patients with bicuspid aortic valve
      and a history of aortic insufficiency tend to develop moderate autograft
      dysfunction during long-term follow up.

PMID- 12056731
TI  - Subvalvular circular annuloplasty as a component of aortic valve repair.
AB  - BACKGROUND AND AIM OF THE STUDY: A recently developed technique of aortic
      annuloplasty, together with immediate postoperative results, are described.
      METHODS: Between June 1998 and October 2000, 26 patients (22 men, four women;
      mean age 59 years) with chronic dominant aortic regurgitation (AR) underwent
      aortic valve repair in which subvalvular circular annuloplasty was used. A
      concomitant repair technique was performed in all patients. Operative results are
      summarized, along with perioperative changes in NYHA status and echocardiographic
      findings. RESULTS: There were no hospital deaths. Mean cardiopulmonary bypass
      time was 139.0+/-32.8 min, and mean aortic cross-clamp time 106.0+/-33.2 min.
      Mean postoperative NYHA class at one month postoperatively was 1.0. Mean
      postoperative AR grade at hospital discharge was 0.9+/-0.7, which represented an
      improvement over preoperative grade (p <0.0001). LVEDD was reduced from 6.3+/-0.9
      cm to 5.1+/-1.1 cm (n = 25; p <0.001), and LVEF from 64.3+/-9.2% to 51.9+/-11.0%
      (n = 26; p <0.0001). Annulus size was reduced from 2.6+/-0.3 cm to 2.2+/-0.2 cm
      (n = 18; p <0.0001). CONCLUSION: A new technique of aortic annuloplasty as a
      component of aortic valve repair was developed and used successfully in 26
      consecutive patients. The short-term postoperative outcome was satisfactory.

PMID- 12056732
TI  - Aortic valve stenosis in alkaptonuric ochronosis.
AB  - Alkaptonuria is a rare genetic disorder of tyrosine metabolism in which a bluish
      pigment accumulates in the connective tissues throughout the body, and causes
      degenerative changes. The most common clinical manifestation of ochronosis is
      arthropathy. Heart valves may also be affected, though cardiac involvement is
      rare. The present patient has cardiac ochronosis, and has several family members
      diagnosed with ochronosis and aortic valve stenosis.

PMID- 12056733
TI  - Ventricular septal defect complicated by infective endocarditis of the aortic
      valve causing severe aortic regurgitation: the role of aortic valve repair.
AB  - BACKGROUND AND AIMS OF THE STUDY: Children with ventricular septal defect (VSD)
      who develop severe aortic regurgitation following infective endocarditis (IE)
      require aortic valve replacement in most cases. Few reports exist of repair of
      the aortic valve under such circumstances. Here, we report details from two
      patients in whom aortic valve repair resulted in a good outcome. METHODS: Two
      children (aged 4 and 3 years) with either perimembranous or doubly committed
      subarterial VSD presented with congestive cardiac failure (NYHA class IV)
      following IE. The aortic valve in both children, and the pulmonary valve in one
      child, were severely damaged with vegetation, leading to severe (grade IV) aortic
      regurgitation. The second patient had bilateral bronchiectasis with respiratory
      infection and severe anemia. In addition to VSD closure, partial cuspal
      replacement using glutaraldehyde-tanned pericardium was performed successfully in
      both cases to restore geometry. RESULTS: Both children showed a dramatic
      improvement following surgery and during follow up of 36 and 11 months,
      respectively. Both remained asymptomatic, with good growth, good left ventricular
      function and the presence of only trivial aortic regurgitation. CONCLUSION: In
      selected patients with suitable anatomy, repair of the aortic valve with
      pericardial cusp replacement may be the procedure of choice. An additional
      benefit is the avoidance of long-term anticoagulation.

PMID- 12056734
TI  - Monodimensional estimation of maximum Reynolds shear stress in the downstream
      flow field of bileaflet valves.
AB  - BACKGROUND AND AIM OF THE STUDY: Turbulent flow generated by prosthetic devices
      at the bloodstream level may cause mechanical stress on blood particles.
      Measurement of the Reynolds stress tensor and/or some of its components is a
      mandatory step to evaluate the mechanical load on blood components exerted by
      fluid stresses, as well as possible consequent blood damage (hemolysis or
      platelet activation). Because of the three-dimensional nature of turbulence, in
      general, a three-component anemometer should be used to measure all components of
      the Reynolds stress tensor, but this is difficult, especially in vivo. The
      present study aimed to derive the maximum Reynolds shear stress (RSS) in three
      commercially available prosthetic heart valves (PHVs) of wide diffusion, starting
      with monodimensional data provided in vivo by echo Doppler. METHODS: Accurate
      measurement of PHV flow field was made using laser Doppler anemometry; this
      provided the principal turbulence quantities (mean velocity, root-mean-square
      value of velocity fluctuations, average value of cross-product of velocity
      fluctuations in orthogonal directions) needed to quantify the maximum turbulence
      related shear stress. RESULTS: The recorded data enabled determination of the
      relationship, the Reynolds stresses ratio (RSR) between maximum RSS and Reynolds
      normal stress in the main flow direction. The RSR was found to be dependent upon
      the local structure of the flow field. CONCLUSION: The reported RSR profiles,
      which permit a simple calculation of maximum RSS, may prove valuable during the
      post-implantation phase, when an assessment of valve function is made
      echocardiographically. Hence, the risk of damage to blood constituents associated
      with bileaflet valve implantation may be accurately quantified in vivo.

PMID- 12056735
TI  - In-vitro verification of the electron beam tomography method for measurement of
      heart valve calcification.
AB  - BACKGROUND AND AIM OF THE STUDY: Electron beam tomography (EBT) has been used
      previously to study aortic root wall and leaflet calcification. However, the
      sensitivity of this method must be validated by comparing EBT findings with
      calcification in the cusps as determined using other techniques. An in-vitro
      study was designed to examine the correlation between EBT scores of
      calcification, visual observations, traditional X-radiography, dual-energy X-ray
      analysis (DEXA) and atomic absorption spectroscopy (AAS). METHODS: Seven
      commercial and experimental pericardial valves were implanted in the mitral
      position in juvenile sheep for up to 20 weeks. Valves were examined thoroughly
      upon explantation and traditional x-radiographs were taken using standard
      techniques and ranked in increasing order of calcification. A calcification score
      in Hounsfield Units (HU) and a calcified volume score in mm3 were calculated for
      each valve by EBT. Calcium content was then calculated by means of DEXA and AAS.
      RESULTS: Calcification scores ranged from 1.03 to 538.93 HU, and calcified volume
      scores from 6.18 to 1804.6 mm3. Correlation analysis showed a good agreement
      between the physical observations, in-vitro traditional X-radiography and both
      the calcification score and calcified volume score. EBT measurements were highly
      correlated with the DEXA examinations (r = 0.98, p = 0.0001 versus calcification
      score; and r = 0.97, p = 0.0003 versus calcified volume score) and AAS analyses
      (r = 0.98, p = 0.0001 versus calcification score; and r = 0.99, p = 0.0000 versus
      calcified volume score). CONCLUSION: These preliminary results indicate a good
      correlation between the physical observations of calcification, X-radiographic
      observations, DEXA, AAS analyses and EBT measures of calcification.

PMID- 12056736
TI  - In-vitro assessment of the wear development mechanism and stabilization of wear
      in the Edwards MIRA/Sorin Bicarbon mechanical heart valve orifice ring.
AB  - BACKGROUND AND AIM OF THE STUDY: Currently, there appears to be no detailed
      published information specifically describing the early 'wear-in' and
      stabilization periods of wear in a bileaflet mechanical heart valve. This study
      presents a detailed morphological description of the early to middle (0 to 200
      million cycles) stages of wear in the Carbofilm carbon coating on the Edwards
      MIRA/Sorin Bicarbon valve housing (orifice ring) pivot slots. METHODS: Wear
      testing was performed using a specially designed durability tester that controls
      the impact load of the occluder against the housing. The control values were
      determined based on simulated physiological pulsatile flow impact loads. A
      morphological assessment of the early wear was performed using light microscopy
      and scanning electron microscopy at intervals of 0.1, 1, 10 and 40 million
      cycles, and at every 40 million cycles thereafter up to 200 million cycles (five
      equivalent years). A quantitative assessment of the rate of Carbofilm removal was
      determined using planimetric methods as a function of cycles. RESULTS: The
      morphology of the Carbofilm wear showed first a gradual thinning of the layer in
      locations in contact with the leaflets, followed by small areas of film removal,
      culminating in slowly increasing areas of exposed titanium alloy substrate.
      Initial substrate exposure began typically between 0.1 million and 10 million
      cycles. The wear rate stabilized at a relatively low value, typically by 40
      million cycles. CONCLUSION: The nature of the early wear development of the
      Edwards MIRA/Sorin Bicarbon valve has been determined as a process of gradual
      thinning of the Carbofilm layer, followed by a decelerating area increase of
      exposed titanium alloy substrate. The process is not one of 'flaking' or spalling
      of relatively large particles. The exposed titanium alloy surface is typically
      smooth and burnished. The wear rate is well behaved and stabilized by
      approximately 40 million cycles. Wear area expansion continues at a decreasing
      rate up to 200 million cycles.

PMID- 12056737
TI  - Risk of reoperation for structural failure of aortic and mitral tissue valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to assess the risk of
      reoperation for patients with a failing stented tissue valve. METHODS: Between
      1980 and 1999, 259 patients (118 males, 141 females; mean age 60.1+/-15.4 years)
      underwent redo valve replacement to replace a failing stented tissue valve. Of
      these patients, 94 (36.3%) underwent redo aortic valve replacement (AVR), 105
      (40.5%) redo mitral valve replacement (MVR), and 60 (23.2%) redo aortic and
      mitral valve replacement (DVR). Twenty patients (7.7%) had previous coronary
      artery bypass grafting (CABG); further CABG were performed in 32 cases (12.4%).
      Preoperatively, 216 patients (83.3%) were in NYHA functional class III or IV.
      RESULTS: The early mortality was (6.5%; n = 17), including three patients who had
      AVR, five DVR, and nine MVR. A higher preoperative NHYA status (p <0.0004) and
      emergency surgery (p <0.0001) were significantly associated with an increased
      risk of operative death (univariate analysis). Age at surgery (p = 0.45),
      previous CABG (p = 0.45), position of the valve replaced (p = 0.2), type of
      implant (p = 0.06) and presence of coronary artery disease (p = 0.51) were not
      associated with a significant risk of operative mortality. Including those
      patients who died, 88 (34.0%) experienced a peri- or postoperative complication,
      seven of which (2.7%) were permanent. CONCLUSION: A failing tissue valve can be
      replaced, with acceptable operative mortality and morbidity. The choice of valve
      is a balance of its advantages and disadvantages, and these must be discussed
      with the patient. It appears, however, that the trend towards reducing the age at
      which tissue valve implantation is performed may be justified.

PMID- 12056738
TI  - Performance of the Carpentier-Edwards SAV and Hancock-II porcine bioprostheses in
      aortic valve replacement.
AB  - BACKGROUND AND AIMS OF THE STUDY: Extended experiences of the Carpentier-Edwards
      Supra-Annular Valve (CE-SAV) and the Hancock II (H II) porcine bioprostheses were
      evaluated to determine the freedom from structural valve deterioration (SVD) by
      reoperation in the aortic position. METHODS: Between 1981 and 1994, 1,524
      procedures (mean patient age 67.6+/-11.2 years) with the CE-SAV, and 670
      procedures (mean patient age 65.2+/-12.1 years) with the H II were conducted at
      the University of British Columbia and University of Toronto, respectively. The
      patient populations were differentiated by mean age, gender and valve size, but
      not by concomitant coronary artery bypass. The analyses included actuarial and
      actual freedom from SVD and evaluation of predictors of SVD. RESULTS: Actuarial
      freedom from SVD at 15 years for patients aged > or =65 years was 91.5+/-2.9% for
      CE-SAV, and 100% for H II (p = NS), while the actual freedom was 96.4+/-1.0% and
      100%, respectively. For the patient population aged 66-70 years, the actuarial
      freedom from SVD was 87.0+/-6.0% for CE-SAV and 100% for H II (p = NS), while the
      actual rates were 93.6+/-2.3% and 100%, respectively. For the population aged >70
      years, the actuarial freedom from SVD was 96.9+/-1.5% for CE-SAV, and 100% for H
      II (p = NS), while the actual freedom was 98.8+/-0.5% and 100%, respectively. In
      the patient population aged <65 years, the actuarial freedom from SVD at 15 years
      favored the H II (p = 0.04), and the actual freedom showed the same outcome. The
      valve type was not predictive of SVD for age groups < or =60 years, >60 years, 61
      70 years and >70 years, but was predictive for the overall population (p = 0.03),
      as was age and previous valve replacement. CONCLUSION: The CE-SAV and Hancock II
      both provide satisfactory clinical performances, with a low incidence of SVD, and
      no significant difference in SVD was shown in patients aged > or =65, 66-70, or
      >70 years. There is a trend to less SVD by actual analysis for the Hancock II in
      patients aged <65 years. This evaluation must be considered as work-in-progress
      because of the limited number of patients at risk at 15 years, especially with
      the Hancock II prosthesis.

PMID- 12056740
TI  - In-vivo bacterial adherence to intracardiac prosthetic materials: a new
      experimental model.
AB  - BACKGROUND AND AIM OF THE STUDY: Bacterial colonization of inert artificial
      materials is a critical variable in the appearance of foreign body-centered
      infections. Hence, a new experimental endocarditis model was evaluated that
      enables quantitative in-vivo testing of bacterial adherence to prosthetic
      materials. METHODS: In 53 rabbits, different patches of either Dacron (DAC; n =
      16), glutaraldehyde-fixed pericardium (GAP; n = 18) or cryopreserved allograft
      (AG; n = 19) were threaded onto a Prolene suture and led through a stitch
      incision at the left atrium to the ventricle, perforating the mitral valve and
      leaving the heart at the outside of the left ventricle. The patch became caught
      in the valve tissue, creating mitral insufficiency. At 6 h after surgery, 6 x
      10(6) colony-forming units (CFU) of Staphylococcus aureus were administered
      intravenously. Postmortem examination and further analysis were carried out 48 h
      after bacterial inoculation. RESULTS: Ten animals (two DAC, four GAP, four AG)
      died and were excluded. Subsequently, sterile patches were found in 6/14 animals
      of the DAC group, in 9/14 of the GAP group, and in 9/15 of the AG group. The mean
      numbers of cultured organisms in the remaining patches were 2.3 x 10(6) + 7.6 x
      10(6)/mg (DAC), 1.8 x 10(4)+/-6.7 x 10(4)/mg (GAP) and 4.9 x 10(5)+/-1.0 x 10(6)
      CFU/mg (AG). Differences in the number of CFU were not significant for all
      groups. CONCLUSION: The above-described model allows reliable quantitative in
      vivo testing of bacterial adherence to different prosthetic materials within a
      short time period. The results suggest that, with regard to avoiding the
      development of bacterial endocarditis, biomaterials have no advantage over
      Dacron.

PMID- 12056739
TI  - Prevalence and predictors of significant coronary artery disease in Turkish
      patients who undergo heart valve surgery.
AB  - BACKGROUND AND AIMS OF THE STUDY: The presence of significant atherosclerotic
      coronary artery disease (CAD) in patients with valvular heart disease is an
      important predictor of perioperative mortality. The prevalence of CAD in patients
      undergoing valvular heart surgery is 20-40% in industrialized countries. The
      study aim was to determine CAD prevalence in Turkish patients undergoing valvular
      heart surgery, and to identify predictors of its presence. METHODS: A total of
      760 patients (357 males, 403 females; mean age 54.4+/-18.1 years) who underwent
      coronary angiography before valvular surgery between 1995 and 2000 was enrolled
      retrospectively. Single- and multi-valve involvement was present in 46% and 54%
      of patients, respectively. Patients with ischemic mitral regurgitation were
      excluded from the study. Significant CAD was defined as the presence of > or =50%
      diameter stenosis anyone of the coronary arteries. The presence of angina
      pectoris, and of risk factors (e.g. hypertension, smoking, diabetes mellitus
      (DM), hyperlipidemia, family history of CAD) were sought in all patients.
      Predictors of CAD were identified by logistic regression analysis. RESULTS:
      Significant CAD was present in 15.8% of patients (24% males, 9% females) (p
      <0.001); the highest prevalence was in those with aortic stenosis (p <0.05). CAD
      was not seen in young patients (aged <45 years) with none of the above-mentioned
      risk factors. The highest correlation between CAD and risk factors was family
      history of CAD, followed by DM, hyperlipidemia, hypertension and smoking, in
      decreasing order. CONCLUSION: The study results showed that CAD in patients with
      valvular heart disease was less prevalent in Turkey than in industrialized
      countries. The incidence of coronary lesions rises notably from the age of 50
      years in both males and females. Coronary angiography before valvular heart
      surgery could be omitted in young patients (age <45 years) with none of the
      coronary risk factors, or without angina.

PMID- 12056741
TI  - Recurrent thrombosis of prosthetic mitral valve in idiopathic hypereosinophilic
      syndrome.
AB  - A 41-year old man, with idiopathic hypereosinophilic syndrome, had severe mitral
      regurgitation. He had two subsequent mechanical mitral valve thromboses in the
      setting of rising eosinophilia. A Carpentier-Edwards bioprosthesis was used for
      the third valve replacement. Some features of myeloproliferative disease,
      including chromosome 10 abnormality, were identified. A normal eosinophil count
      and disappearance of the chromosomal abnormality were obtained with interferon,
      hydroxyurea and prednisone therapy. At 30 months postoperatively, the patient had
      a normal lifestyle.

PMID- 12056742
TI  - In response to Mitchell RN. Don't blame the lymphocyte: immunologic processes are
      not important in tissue valve failure. J Heart Valve Dis 2001;10:467-470.

PMID- 12056743
TI  - In response to Lengyel M, Vandor L. The role of thrombolysis in the management of
      left sided obstructive prosthetic valve thrombosis--is there a case for it? J
      Heart Valve Dis 2001;10:638-649.

PMID- 12056744
TI  - In response to Cotrufo M, Carozza A, Romano G, De Feo M, Della Corte A. Infective
      endocarditis of native cardiac valves: 22 years' surgical experience. J Heart
      Valve Dis 2001;10:478-485.

PMID- 12056745
TI  - The long and short of sperm polymorphisms in insects.
AB  - Production of more than one morphological type of sperm in a common testis has
      been documented for a variety of invertebrates, including gastropods, spiders,
      centipedes, and insects. This unusual phenomenon is difficult to explain by
      current theory, particularly since available evidence indicates that one sperm
      type is often incapable of effecting fertilization. In this review we critically
      examine evidence on the distribution and development of sperm heteromorphisms
      among insects in light of competing hypotheses for the evolutionary origin,
      maintenance, and function of a non-fertilizing class of sperm. To date, no single
      hypothesis, including alternatives which assume non-fertilizing sperm are non
      adaptive, or that they provision, facilitate, or compete with fertilizing sperm,
      has received strong empirical support by any group of insects. The diversity of
      sperm heteromorphisms suggests that non-fertilizing sperm may have different
      functions in different clades or even serve multiple functions within a clade. We
      suggest that insight could be gained from (1) new models for the evolution of
      sperm polymorphism, (2) comparative studies that focus on multiple traits
      simultaneously (e.g. sperm number, proportion, length, and remating rate) and
      utilize clades in which more than one gain or loss of sperm heteromorphism has
      been documented (e.g. Pentatomidae, Carabidae, or Diopsidae), and (3)
      experimental studies that exploit individual variation or directly manipulate the
      composition of the male ejaculate.

PMID- 12056746
TI  - The sexually-selected sperm hypothesis: sex-biased inheritance and sexual
      antagonism.
AB  - When females are inseminated by more than one male (polyandry) sexual selection
      continues after insemination in the form of sperm competition and cryptic female
      choice. The sexually-selected sperm hypothesis proposes that, under the risk of
      sperm competition, additive variation in male traits determining fertilising
      efficiency will select for female propensity to be polyandrous in order to
      increase the probability of producing sons with superior fertilising efficiency.
      Two factors complicate this prediction: sex-biased transmission of male
      fertilising efficiency traits and sexual antagonism of sex-limited traits,
      fostered by sex-biased inheritance. Here, we (i) review the evidence that male
      traits contributing towards fertilising efficiency are heritable through sex
      biased mechanisms, and (ii) explore the evolutionary implications for male and
      female reproductive strategies caused by both sex-biased transmission and sexual
      antagonism of fertilising efficiency traits. Many male fertilising efficiency
      traits are heritable through sex-biased mechanisms and may not necessarily
      increase female fitness. The predictions of the sexually-selected sperm
      hypothesis change dramatically under these different mechanisms of inheritance of
      fertilising efficiency traits, and different fitness pay-offs derived by females
      from the expression of such traits. Both sex-biased control of fertilising
      efficiency and sexual antagonism may also be important in explaining the
      maintenance of the genetic variance and selection potential of fertilising
      efficiency. We propose that a useful approach to test the sexually-selected sperm
      hypothesis is to combine studies which identify behavioural and physiological
      mechanisms explaining variation in reproductive success with artificial selection
      experiments to infer the underlying evolutionary patterns.

PMID- 12056747
TI  - Publication bias in ecology and evolution: an empirical assessment using the
      'trim and fill' method.
AB  - Recent reviews of specific topics, such as the relationship between male
      attractiveness to females and fluctuating asymmetry or attractiveness and the
      expression of secondary sexual characters, suggest that publication bias might be
      a problem in ecology and evolution. In these cases, there is a significant
      negative correlation between the sample size of published studies and the
      magnitude or strength of the research findings (formally the 'effect size'). If
      all studies that are conducted are equally likely to be published, irrespective
      of their findings, there should not be a directional relationship between effect
      size and sample size; only a decrease in the variance in effect size as sample
      size increases due to a reduction in sampling error. One interpretation of these
      reports of negative correlations is that studies with small sample sizes and
      weaker findings (smaller effect sizes) are less likely to be published. If the
      biological literature is systematically biased this could undermine the attempts
      of reviewers to summarise actual biology relationships by inflating estimates of
      average effect sizes. But how common is this problem? And does it really affect
      the general conclusions of'literature reviews? Here, we examine data sets of
      effect sizes extracted from 40 peer-reviewed, published meta-analyses. We
      estimate how many studies are missing using the newly developed 'trim and fill'
      method. This method uses asymmetry in plots of effect size against sample size
      ('funnel plots') to detect missing' studies. For random-effect models of meta
      analysis 38% (15/40) of data sets had a significant number of 'missing' studies.
      After correcting for potential publication bias, 21 % (8/38) of weighted mean
      effects were no longer significantly greater than zero, and 15% (5/34) were no
      longer statistically robust when we used random-effects models in a weighted meta
      analysis. The mean correlation between sample size and the magnitude of
      standardised effect size was also significantly negative (r(s) = -0.20, P <
      0.0001). Individual correlations were significantly negative (P<0.10) in 35%
      (14/40) of cases. Publication bias may therefore affect the main conclusions of
      at least 15-21% of meta-analyses. We suggest that future literature reviews
      assess the robustness of their main conclusions by correcting for potential
      publication bias using the 'trim and fill' method.

PMID- 12056748
TI  - A phylogenetic supertree of the bats (Mammalia: Chiroptera).
AB  - We present the first estimate of the phylogenetic relationships among all 916
      extant and nine recently extinct species of bats Mammalia: Chiroptera), a group
      that accounts for almost one-quarter of extant mammalian diversity. This
      phylogeny was derived by combining 105 estimates of bat phylogenetic
      relationships published since 1970 using the supertree construction technique of
      Matrix Representation with Parsimony (MRP). Despite the explosive growth in the
      number of phylogenetic studies of bats since 1990, phylogenetic relationships in
      the order have been studied non-randomly. For example, over one-third of all bat
      systematic studies to date have locused on relationships within Phyllostomidae,
      whereas relationships within clades such as Kerivoulinae and Murinae have never
      been studied using cladistic methods. Resolution in the supertree similarly
      differs among clades: overall resolution is poor (46.4%, of a fully bifurcating
      solution) but reaches 100% in some groups (e.g. relationships within
      Mormoopidae). The supertree analysis does not support a recent proposal that
      Microchiroptera is paraphyletic with respect to Megachiroptera, as the majority
      of source topologies support microbat monophyly. Although it is not a substitute
      for comprehensive phylogenetic analyses of primary molecular and morphological
      data, the bat supertree provides a useful tool for future phylogenetic
      comparative and macroevolutionary studies. Additionally, it identifies clades
      that have been little studied, highlights groups within which relationships are
      controversial, and like all phylogenetic studies, provides preliminary hypotheses
      that can form starting points for future phylogenetic studies of bats.

PMID- 12056749
TI  - Filial cannibalism in teleost fish.
AB  - This review summarizes information on filial cannibalism (the act of eating one's
      own offspring) in teleost fish. Cannibalistic parents can either consume their
      whole brood (total filial cannibalism), or eat only some of the eggs in the nest
      (partial filial cannibalism). Offspring consumption has been argued to be
      adaptive under the assumption that offspring survival is traded against feeding,
      and that offspring can act as an alternative food source for the parents. The
      evidence supporting the basic predictions formulated under these assumptions is
      summarized for both total and partial filial cannibalism. These two forms of
      cannibalism differ significantly since the former represents an investment only
      in future reproductive success, whereas the latter can affect both present and
      future reproductive success. Despite a few inconsistencies in the data from
      laboratory and field studies, the energy-based explanation appears valid for both
      forms of cannibalism. Alternative non-energy-based explanations are considered,
      but they are unable to account for the wide distribution of this behaviour in
      teleosts. The intersexual conflict arising from attempts of the non-cannibal sex
      to minimize the cost of filial cannibalism is also discussed, together with the
      potential effect of this behaviour on the operational sex ratio at a population
      level.

PMID- 12056750
TI  - Immunohistochemical investigations of the autonomous nerve distribution in the
      testis of the camel (Camelus dromedarius).
AB  - The distribution of autonomous nerves in the testis of the camel was studied by
      immunohistochemical methods. A total of 26 testes was collected during the
      different seasons of the year. As pan-neuronal markers, antibodies to protein
      gene product 9.5 and to neurofilaments are superior to antibodies against neuron
      specific enolase and acetylcholinesterase histochemistry for the description of
      the nerves in the camel testis. Testicular nerves reach the camel testis by three
      access-routes as (1) funicular contribution, (2) mesorchial contribution and (3)
      as caudal contribution. The main target for testicular nerves is the arterial
      vascular tree of the organ, whereas all veins of testis and pampiniform plexus
      are devoid of any innervation in the camel. In the wall of the arteries, the
      nerves form a plexus at the media-adventitia border. The density of the arterial
      plexuses increases along the vascular tree: smaller septal and mediastinal
      arteries are better innervated than albugineal arteries and the latter better
      than the A. testicularis. The nerves in the septula testis, in the mediastinum
      and between the Leydig cells show clear seasonal changes, being particularly
      abundant in autumn and particularly scarce in spring. The nerves that reach the
      camel testis are unmyelinated and represent in the vast majority postjunctional
      sympathetic neurons. Cholinergic fibers are absent in the camel testis.
      Neuropeptide Y is the dominating peptidergic transmitter in the testicular nerves
      and colocalized with noradrenaline in the same axons. Vasoactive intestinal
      polypeptide-containing fibers reach the camel testis exclusively as parts of the
      caudal nervous contribution via the ligamentous bridge between testis and
      epididymal tail and are restricted to the caudal pole of the testis. Calcitonin
      gene-related peptide-positive axons are not frequent in the camel testis;
      nevertheless, they seem to be the most important sensory pathway of this organ.

PMID- 12056752
TI  - The architecture of growing compact bone in the dog: visualization by 3D
      reconstruction of histological sections.
AB  - The three-dimensional architecture of growing canine compact bone was
      investigated by generating a composite virtual model including both cellular and
      extracellular elements. Serial trichrome-stained histological sections were
      prepared from samples of the diaphysis of the humerus of six week old Beagle
      puppies. Identical fields of vision were recorded in consecutive sections,
      preprocessed in Adobe Photoshop 5.5, and then transferred into the program
      AVS/Express for 3D-reconstruction and visualization. Based on two different but
      integrated reconstruction techniques a hybrid model was created, depicting shape
      and orientation of bony trabeculae as well as the distribution of osteoblasts.
      This virtual model could be explored and navigated in with real time
      interactivity, and thus disclosed the specific architectural characteristics of
      immature compact bone. In young puppies, bone tissue of the corpus humeri forms a
      labyrinth of communicating osseous walls which are covered with a multitude of
      osteoblasts. These results are discussed in relation to findings in adult dogs.

PMID- 12056751
TI  - Ultrastructural study of cell-cell interaction between osteoclasts and
      osteoblasts/stroma cells in vitro.
AB  - Many biochemical reports support cell-cell interaction between osteoclasts and
      osteoblasts/stroma cells in vitro, however there have been few morphological
      studies supporting this. Details of cell-cell interaction between osteoclasts and
      osteoblasts/stroma cells remain unclear. The present study examined cell-cell
      interaction between osteoclasts and osteoblasts/stroma cells by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). Osteoclasts,
      osteoblasts/stroma cells, and bone marrow cells obtained from 10-day-old ddY mice
      were cultured on dentin slices for 72 hr. Specimens were fixed, and some were
      examined by SEM. Specimens were decalcified, embedded in Epon after determination
      of the tartrate-resistant acid phosphatase activity (TRAP), and TRAP-positive
      cells for investigation were serially sectioned by alternating semithin and
      ultrathin sections, and then examined by TEM. By SEM, many cellular contacts were
      seen between the cells cultured on the dentin, but by TEM there were few special
      structures on the cell membranes between osteoclasts and osteoblasts/stroma
      cells, or between osteoclasts and bone marrow cells. A special structure on the
      cell membranes of osteoclasts was observed between an osteoclast and a
      cytoplasmic process of osteoblast/stroma cells, and this cell membrane was coated
      with electron dense or bristle-like structures. These bristle-like structures
      were very similar to those of coated pits. The present results show that the
      coated pit-like structure plays an important role in cell-cell interaction
      between osteoclasts and osteoblasts/stroma cells in vitro, and suggest that
      macromolecules binding to the osteoclast-surface receptor via ligands, accumulate
      in the coated pits, and enter the osteoclast as receptor-macromolecule complexes
      in endocytic vesicles.

PMID- 12056753
TI  - Substance P and calcitonin gene-related peptide immunoreactive sensory DRG
      neurons innervating the lumbar intervertebral discs in rats.
AB  - The rat L5/6 disc is innervated from T13 to L6 dorsal root ganglia (DRGs)
      multisegmentally. Sensory fibers from T13, L1 and L2 DRGs have been reported to
      innervate through the paravertebral sympathetic trunks, whereas those from L3 to
      L6 DRGs innervate directly through sinuvertebral nerves on the posterior
      longitudinal ligament (PLL). The presence of substance P (SP)- and calcitonin
      gene-related peptide (CGRP)-immunoreactive (ir) nerve fibers has been
      demonstrated in the lumbar intervertebral discs, but their percentages in DRG
      neurons have not been studied. Fluoro-gold (F-G) labeled neurons innervating the
      L5/6 disc were distributed throughout DRGs from T13 to L6 levels. Of F-G labeled
      neurons innervating the L5/6 disc, the percentage of SP-ir T13 to L6 DRG neurons
      was 30%, and that of CGRP-ir neurons was 47%. The mean cross-sectional area of
      the cell of SP-ir neurons was 696+/-66 microm2 (mean +/- S. E.), and that of CGRP
      ir neurons was 695+/-72 microm2 (mean +/- S. E.). SP- and CGRP-ir were mainly
      observed in small neurons. The percentages of SP- or CGRP-ir neurons in L1 and L2
      DRGs innervating the L5/6 disc were not different from those in L3, L4 or L5
      DRGs. In the physiological condition in rats, DRG neurons at all levels may have
      the same significant role in pain sensation of the disc.

PMID- 12056754
TI  - Bone remodeling analysis after placement of dental implants using
      polyfluorochrome sequential labeling.
AB  - Nowadays there is a general consensus related to the stability of dental implants
      during bone repair. The implant anchorage in the bone is very important for the
      stability of the element that has to support much pressure when under use. This
      stability is attained by bone modeling and remodeling processes. As it is known,
      the implant/bone interface does not present the ideal result expected by every
      professional. The possibility of stimulation of the bone formation at the
      interface and around titanium implants is based on the reaction of the bone to
      trauma due to the surgical procedure. This bone reaction leads to bone repair
      during healing. The purpose of this study is to analyze the efficiency of bone
      tissue labeling through polyfluorochrome sequential labeling during remodeling or
      neo-formation processes after the placement of smooth threaded implants used in
      dentistry. This work demonstrates the possibility of periodic deposition of bone
      identification around titanium osseointegrated implants. It was concluded that
      the polyfluorochrome sequential labeling is an important tool to identify bone
      modeling and remodeling after the insertion of titanium implants inside rabbit's
      tibias at different periods of time.

PMID- 12056755
TI  - On-block UV light polymerization of LR Gold-embedded flat-mounted tissue using
      low temperature modules.
AB  - A problem associated with low temperature embedding is due to the fact that
      suitable resins have to be polymerized under oxygen-free atmosphere, thus making
      the complete filling and tight sealing of vials or capsules essential.
      Particularly with thin tissue sections or retinal flat-mounts it is rather
      difficult to obtain flat-embedded specimens under these conditions. To overcome
      this problem, we have designed a low temperature module (LTM) that allows the
      polymerization of flat tissue probes on faced resin blocks using UV light, thus
      instantly creating ready specimens with an almost planar surface. To test the
      device, vibratome sections of the rat superior colliculus were embedded in LR
      Gold and UV-cured in LTMs. Electron microscopy revealed a good preservation of
      the fine structure. The new UV light polymerization technique proved to be highly
      suitable to obtain ultrathin sections being cut parallel to the surface of the
      embedded material, an advantageous feature for applications which necessitate the
      examination of specifically oriented or laminated structures. Detailed and
      dimensioned drawings of the LTM can be downloaded as a PDF file at:
      http://www.uni-leipzig.de/-vetana.

PMID- 12056756
TI  - SEM examination of the dorsal lingual papillae of pregnant rats.
AB  - To our knowledge there are no histomorphological studies examining the lingual
      papillae in pregnancy. Therefore, this present study was planned. The purpose of
      this study was to clarify different physiological results and to investigate
      whether there are any changes on the dorsal surface of the rat tongue during
      pregnancy. On days 7 and 14 of pregnancy, superficial epithelial configurations
      of the lingual papillae (circumvallate, fungiform, filiform) in pregnant rats
      were examined by scanning electron microscopy (SEM). It was found that there were
      some differences in topographic configurations of these papillae in pregnant rats
      compared with controls. The obtained changes by SEM may reflect something which
      occurs in the lingual papillae during pregnancy in rat. There may be a
      correlation between the alterations of some hormone levels in pregnancy and some
      morphological changes of the lingual papillae.

PMID- 12056757
TI  - The effect of hand preference on hand anthropometric measurements in healthy
      individuals.
AB  - This study was planned for the purpose of investigating the effect of hand
      preference on hand anthropometric measurements, with the participation of 393
      healthy university students. The hand preference direction of the subjects was
      established according to the Edinburgh Inventory, and five hand preference
      determination groups were constituted after calculation of the laterality score.
      During performance of the hand anthropometric measurements, values for both hands
      were calculated, and seven parameters were evaluated for each hand. Hand width
      and shape index were found to be high for the right hand, but the palmar
      length/width ratio was found to be high for the left hand, for strong and weak
      right handers, respectively. No significant statistical values were obtained
      among ambidextrous subjects, although their parameters resembled these groups'
      values. Additionally, in the left-handed group, reverse direction asymmetric
      values were established, but significant statistical values were not obtained. An
      increase in right and left hand asymmetry was established going from the strong
      right hand preferent group to the strong left hand preferent group (on a
      decreasing scale of right hand preference). If the laterality score is evaluated
      without regard to groups, left hand shape index and right hand finger index may
      be accepted as phenotype indicators of hand preference. Left hand shape index and
      right hand finger index increased in correlation with the tendency for left hand
      and right hand preference, respectively. The findings reveal that, environmental
      factors such as hand activity, hormones, and brain asymmetry may play a role in
      the effect of hand preference on hand anthropometric measurements. In our study,
      we found no difference in asymmetry in regard to the sex of the subjects,
      generally.

PMID- 12056758
TI  - An unusual termination of the ulnar nerve in the palm.
AB  - During the dissection of the left forearm and hand of a 57-year old male cadaver
      fixed in 10% formalin, it has been noted that the medial proper palmar digital
      nerve to the little finger arose from the dorsal branch of the ulnar nerve,
      instead of the superficial branch of the same nerve. The dorsal branch, given off
      by the ulnar nerve in the forearm, coursed distally and dorsally deep to the
      flexor carpi ulnaris muscle. Some 2 cm proximal to the pisiform, it pierced the
      deep fascia on the posteromedial side of the muscle to become superficial. At
      this point, one of the three branches given off travelled distally on the palmar
      ulnar side of the hand to the skin of the little finger. There were connections
      between this branch and the branches of the superficial branch of the ulnar nerve
      which innervated the skin of the hypothenar eminence. Further, another branch of
      the superficial branch of the ulnar nerve passed under the fibrous arch of the
      flexor digiti minimi brevis muscle origin and the opponens digiti minimi muscle
      to re-unite with its parent nerve.

PMID- 12056759
TI  - The origin of gonadal arteries in human fetuses: anatomical variations.
AB  - Testicular arterial anatomy has been well studied because of its importance in
      testicular physiology, as well as testicular and renal surgery. In contrast to
      classical anatomical descriptions, it may originate from the suprarenal or lumbar
      arteries or a high-positioned origin, course behind the inferior vena cava or be
      doubled or arise from an inferior polar renal artery. Different developmental
      patterns as variations in relation to origin, course and number of the renal and
      gonadal arteries have been reported and discussed. This study was performed on 90
      spontaneously aborted fetuses obtained from two different hospitals in Konya. The
      study was carried out on the testicular or ovarian arteries of fetuses fixed by
      immersion in 10% formalin. In all, 180 gonadal arteries were studied and 16 of
      them were found to have variations in their origin (8.8%). The variations of the
      gonadal artery origins could be classified into four types. The gonadal artery
      variations were more commonly found in male than the female fetuses and on the
      right side rather than the left. In the present study, it is clear that these
      variations are important not only from the developmental point of view or
      research interest, but they also may explain some pathological conditions.
      Knowledge of these variations may help to avoid the clinical complications
      especially during radiological examinations and/or surgical approaches in this
      region.

PMID- 12056761
TI  - Ontogeny and occurrence of the corpus fibulae in the domesticated goat (Capra
      aegagrus f. hircus).
AB  - Osteological characteristics are often used to identify animal species in a cheap
      and rapid manner. In this context it is believed that the corpus fibulae of the
      goat is represented by a tight cord of connective tissue--the so-called
      ligamentum fibulare. The results of the present morphometric study indicate,
      however, that in nearly 60% of the 143 examined animals, the corpus fibulae is a
      pin-shaped flattened piece of bone which may additionally be accompanied by a
      pyramid-shaped bone lying closely to the caput fibulae. The length of the corpus
      fibulae increases with age and varies greatly between individuals but its centre
      is located close to the border between the proximal and the intermediate third of
      the tibia. The cartilaginous fetal anlage is either transformed to bone or
      catabolised during fetal live. Desmal ossification should play an important role
      in the growth of the corpus fibulae since no cartilage could be detected in kids
      and adult goats.

PMID- 12056760
TI  - The frenula of the papilla ilealis of the swine.
AB  - The junction between the small and the large intestines has been studied in
      several animals since this region makes an important intestinal transition. Like
      humans the swine have a structure that forms a boundary between the cecum and the
      ascending colon - the frenulum papillae ilealis dorsalis and ventralis.
      Nevertheless the morphology and physiology of this is poorly known. The aim of
      this work is to describe the morphology of the swine's frenula and to trace some
      elements of comparative anatomy. The macroscopic research was done on 33 animals
      and the results were analyzed by Wilcoxon test. The arrangement of the tunica
      muscularis was studied in 12 animals by dissection, after immersion in 50% nitric
      acid solution, and the light microscopic studies were performed in 15 animals. In
      all of the cases it was observed that it was the frenulum papillae ilealis,
      dorsal and ventral, which formed the internal boundary between the cecum and the
      ascending colon. They were constituted of the tunica mucosa, tela submucosa and
      tunica muscularis of the large intestine. The swine's frenula papillae ilealis
      participate in the functioning of the ileocecocolic "pylorus". The macro- and
      microscopic morphology of the swine's frenula are similar to that of the man,
      indicating that this animal would be a good model for the experimental studies.

PMID- 12056763
TI  - Medical licensing examinations in the United States.

PMID- 12056762
TI  - Anatomy during the Third Reich--the Institute of Anatomy at the University of
      Marburg, as an example.
AB  - A complete documentation of German anatomical science and its representatives
      during the period of national socialism has not been published as yet--contrary
      to the situation in other medical disciplines. Instead of German anatomists,
      American anatomists have occasionally addressed this issue during their meetings
      and have reported on special aspects, such as the use of Nazi symbols in
      anatomical textbooks and atlases (Pernkopf 1952) and the use of corpses of
      justice victims for anatomical research and student education. Also, the genesis
      of the atrocious collection of "racial" skulls, initiated along with the SS
      institution of the "Ahnenerbe" by the anatomist August Hirt of Strasbourg (who
      ordered more than 90 inmates from concentration camps to be murdered in the gas
      chamber built in the concentration camp of Natzweiler-Struthof close to
      Strasbourg, Alsace) has been described by Frederic Kasten and others. A broader
      view of the patterns of behaviour and political actions and fates of contemporary
      scientists, ranging from dismissal to clandestine opportunism, affirmative
      cooperation and fanatic activism can be obtained by the analysis of the
      activities in research, medical education and academic positions of the following
      members of the Institute of Anatomy at the Philipp-University in Marburg: Ernst
      Goppert, Eduard Jacobshagen, Ernst-Theodor Nauck, Adolf Dabelow, Helmut Becher
      and Alfred Benninghoff, whose activities and fates differ in several respects and
      allow more general deductions. Also, the individual fates of a number of
      prosecuted Jewish anatomists (Wassermann, Munchen; Poll, Hamburg), of devoted and
      active members of the Nazi party (Clara, Leipzig; Blotevogel, Breslau) and of
      criminal fanatics (Hirt, Strasbourg; Kremer, Munster) are briefly discussed. The
      present contribution is an attempt to initiate a more detailed study of all
      German departments of anatomy during the Hitler regime and to generate a public
      discussion among the younger generation of German anatomists.

PMID- 12056764
TI  - Patients on clinical board examinations: an examiner's perspective.

PMID- 12056766
TI  - The Cochrane Collaboration: the Oral Health Group.

PMID- 12056765
TI  - Banning live patients as test subjects on licensing examinations.
AB  - The use of live patients on the licensing examinations was a part of dentistry
      for almost the entire twentieth century and continues up until today.
      Considerable new debate about the appropriateness of using live patients as test
      subjects began in the mid-1990s and culminated in the passage of a resolution in
      the American Dental Association's year 2000 House of Delegates calling for an end
      to this practice by the year 2005. The live patient examination tests a narrow
      range of clinical skills, creates ethical dilemmas for candidates, for the host
      institution, and for the profession, and is unable to distinguish between those
      ready to assume independent practice from those who are not yet at that level of
      competence. There are other ways to test for such readiness including proposals
      in New York State to substitute a postdoctoral year or mannequins in place of
      live subjects. The public and the dental profession will be better off by
      developing alternative licensing tests to the use of live subjects.

PMID- 12056767
TI  - A HIPAA strategy for dental schools.
AB  - Certain health care organizations, including dental schools, should be readying
      themselves to comply with the numerous requirements described within the
      administrative simplification section of the Health Insurance Portability and
      Accountability Act of 1996 (HIPAA). The intent of administrative simplification
      is to streamline the management of health care transactions while protecting the
      privacy of certain written, oral, and electronic patient information. There are
      no field-tested plans for implementing the law because only recently has the
      health care industry begun to respond to the multitude of requirements. It is
      essential that each organization create a customized compliance plan that best
      fits its structure and needs. The purpose of this paper is to propose a five
      stage theoretical strategy that could assist a dental school in achieving HIPAA
      compliance. The first stage involves the selection of a HIPAA task force. The
      second stage selects the applicable HIPAA requirements, determines the current
      states of confidentiality and security, manages the electronic transactions
      standards, and composes a gap analysis. The third stage examines risk analysis
      and management. The fourth stage encompasses technical modifications, policies
      and procedures, legal input, and training. The fifth stage addresses the
      maintenance of the implementation.

PMID- 12056768
TI  - Electronic patient records for dental school clinics: more than paperless
      systems.
AB  - The Electronic Patient Record (EPR) or "computer-based medical record" is defined
      by the Patient Record Institute as "a repository for patient information with one
      health-care enterprise that is supported by digital computer input and integrated
      with other information sources." The information technology revolution coupled
      with everyday use of computers in clinical dentistry has created new demand for
      electronic patient records. Ultimately, the EPR should improve health care
      quality. The major short-term disadvantage is cost, including software,
      equipment, training, and personnel time involved in the associated business
      process re-engineering. An internal review committee with expertise in
      information technology and/or database management evaluated commercially
      available software in light of the unique needs of academic dental facilities.
      This paper discusses their deficiencies and suggests areas for improvement. The
      dental profession should develop a more common record with standard diagnostic
      codes and clinical outcome measures to make the EPR more useful for clinical
      research and improve the quality of care.

PMID- 12056769
TI  - The effectiveness of a Mock Board experience in coaching students for the Dental
      Hygiene National Board Examination.
AB  - A Mock Board is available through the American Dental Association to any student
      or dental hygiene program as a study aid for the Dental Hygiene National Board
      Examination (DHNBE). The purpose of this study was to evaluate the usefulness of
      this Mock Board as a learning activity to help students gain familiarity with the
      question formats and the overall board exam experience. A sensitivity-specificity
      model was applied to validate the Mock Board's accuracy in identifying students
      who would pass or fail the DHNBE. A survey was conducted to assess students'
      opinions of the Mock Board experience. The Mock Board accurately identified
      success or failure on the DHNBE for 75 percent of the participants. However, the
      Mock Board's sensitivity was much better than its specificity. A majority of
      students reported the Mock Board motivated them to study and prepared them well
      for the national board experience. Comments showed, however, that students did
      not feel the Mock Board experience was as intense as taking the DHNBE. Findings
      indicate the Mock Board can be a valid and effective addition to board
      preparation activities. Dental hygiene faculty members are urged to consider
      incorporating the Mock Board experience with more traditional methods of coaching
      in preparing students for the DHNBE.

PMID- 12056770
TI  - Web-based orthodontic instruction and assessment.
AB  - Orthodontic records-study models, panoramic and cephalometric radiographs, and
      the patient's facial and intraoral photographs-are used to collect data to
      establish a diagnosis and to develop problem-solution lists. These records,
      however, can be damaged or lost when dispensed to students and need to be stored
      and maintained every year. An orthodontic diagnosis web site, therefore, has been
      set up using digital records to provide students with an accessible source of
      complete, good-quality study materials. The web site is also used for clinical
      examination in orthodontic courses. The effectiveness of the web-based digital
      records in providing relevant information to students in comparison to the
      traditional records was evaluated by a randomized controlled trial involving
      ninety-nine second-year dental students. One group (fifty students) studied two
      cases from the web site; the other group (forty-nine students) studied the same
      two cases from traditional orthodontic records. Effectiveness was assessed by
      comparing test scores and the time spent on the tests by t-statistics. There were
      no significant differences between means for the two study groups in test
      performance or time. Attitudes of students toward the web site, assessed from
      post-test questionnaires, were positive. It was concluded that web-based digital
      orthodontic records were as effective in teaching clinical orthodontic diagnosis
      as were conventional records.

PMID- 12056772
TI  - Post-mortem findings and causes of death of harbour porpoises (Phocoena phocoena)
      stranded from 1990 to 2000 along the coastlines of Belgium and Northern France.
AB  - Between the years 1990 and 2000, an attempt was made to determine the causes of
      death of 55 harbour porpoises stranded along the Belgian and northern French
      coasts. From 1990 to 1996, only five carcasses were collected as against seven in
      1997, eight in 1998, 27 in 1999 and eight in 2000. The sex ratio was normal and
      most of the animals were juvenile. The most common findings were emaciation,
      severe parasitosis and pneumonia. A few cases of fishing net entanglement were
      observed. The main microscopical lesions were acute pneumonia, massive lung
      oedema, enteritis, hepatitis and gastritis. Encephalitis was observed in six
      cases. No evidence of morbillivirus infection was detected. Pneumonia was
      associated with bacteria or parasites, or both. The causes of death and the
      lesions were similar to those previously reported in other countries bordering
      the North Sea. The cause of the increased numbers of carcasses in 1999 was
      unclear but did not include viral epizootics or net entanglement. A temporary
      increase in the porpoise population in the southern North Sea may have been
      responsible.

PMID- 12056771
TI  - The genome projects: implications for dental practice and education.
AB  - Information from the Human Genome Project (HGP) and the integration of
      information from related areas of study and technology will dramatically change
      health care for the craniofacial complex. Approaches to risk assessment and
      diagnosis, prevention, early intervention, and management of craniofacial
      conditions are and will continue to evolve through the application of this new
      knowledge. While this information will advance our health care abilities, it is
      clear that the dental profession will face challenges regarding the acquisition,
      application, transfer, and effective and efficient use of this knowledge with
      regards to dental research, dental education, and clinical practice. Unraveling
      the human genomic sequence now allows accurate diagnosis of numerous craniofacial
      conditions. However, the greatest oral disease burden results from dental caries
      and periodontal disease that are complex disorders having both hereditary and
      environmental factors determining disease risk, progression, and course. Disease
      risk assessment, prevention, and therapy, based on knowledge from the HGP, will
      likely vary markedly for the different complex conditions affecting the head and
      neck. Integration of Information from the human genome, comparative and microbial
      genomics, proteomics, bioinformatics, and related technologies will provide the
      basis for proactive prevention and intervention and novel and more efficient
      treatment approaches. Oral health care practitioners will increasingly require
      knowledge of human genetics and the application of new molecular-based diagnostic
      and therapeutic technologies.

PMID- 12056773
TI  - Immunohistochemical characterization of tuberculous and non-tuberculous lesionsin
      naturally infected European badgers (Meles meles).
AB  - A panel of species cross-reactive antibodies was established for the
      immunohistochemical labelling of phagocytic and lymphoid cells in formalin-fixed
      normal badger tissues. These reagents were used to investigate the
      immunopathogenesis of both tuberculous and non-tuberculous granulomas in badgers.
      In normal badger tissues, antisera specific for the CD79a and CD79b epitopes
      strongly labelled follicular B lymphocytes and plasma cells in lymph nodes,
      bronchus-associated lymphoid tissue and Peyer's patches. Rabbit anti-dog IgG, IgM
      and IgA, and goat anti-human lambda light chain strongly labelled plasma cells,
      but goat anti-ferret IgA produced weak labelling. Interfollicular and occasional
      follicular lymphocytes and gut intraepithelial lymphocytes expressed the CD3
      epitope. Mouse anti-human HLA-DR (MHC Class II) antigen strongly labelled
      macrophages, some follicular lymphocytes and some intestinal and respiratory
      epithelial cells. Mouse anti-human calprotectin (MAC387) labelled a limited
      number of macrophages. In infected badgers, all fusiform to angular macrophages
      (epithelioid cells) of all tuberculous granulomas strongly expressed HLA-DR
      antigen, but only a small, variable proportion of these were labelled by MAC387
      antiserum. Lymphocytes in the peripheral rims of granulomas and those scattered
      sparsely amongst the epithelioid cells were labelled primarily with CD3
      antiserum. Peripheral plasma cells were more common in larger than in smaller
      tubercles and usually expressed IgA or IgG. Small unencapsulated siliceous
      granulomas, which were present in both tuberculous and non-tuberculous badgers,
      consisted of aggregates of round to polyhedral epithelioid cells expressing the
      MHC Class II but not the MAC387 epitope. Granulomas caused by infection with
      presumed fungal adiaspores of Chrysosporium sp. consisted of aggregates of
      variably shaped macrophages that expressed MHC Class II antigen, but only a
      proportion expressed MAC387 antigen. The majority of lymphocytes within the
      peripheral rims of these granulomas were T cells, accompanied by sparse to
      moderate numbers of plasma cells that primarily expressed IgG or IgA. In
      conclusion, species cross-reactive antibodies can be used to identify the
      cellular components of tuberculous and non-tuberculous granulomas.
      Immunohistochemical examination failed to distinguish small tuberculous
      granulomas from adiaspiromycotic granulomas.

PMID- 12056774
TI  - Oncocytic metaplasia of canine palatine ductal epithelium.
AB  - Oncocytic metaplasia of palatine gland ducts was demonstrated by light and
      electron microscopy in seven out of 54 dogs. Oncocytes were recognized as
      distinct swollen epithelial cells with bright eosinophilic cytoplasm, small dark
      nuclei and scattered microvilli at the luminal surface. Their cytoplasm contained
      numerous tightly packed mitochondria, which varied in size and shape. Some
      oncocytes formed nodular hyperplastic foci that were easily recognized by low
      power light microscopy. Oncocytic metaplasia appears to be a common incidental
      finding in palatine ductal epithelium of older dogs.

PMID- 12056775
TI  - Expression of matrix metalloprotease-2 (MMP-2) and the activator membrane type 1
      (MT1-MMP) in canine mammary carcinomas.
AB  - An immunohistochemical approach was used to examine the expression of MMP-2 and
      the activator MT1-MMP in a series of 50 canine mammary carcinomas of different
      histotype and stage. MMP-2 and MT1-MMP were mainly expressed in the cytoplasm of
      carcinoma cells and in fibroblasts. Immunolabelling for both MMP-2 and MT1-MMP
      was also seen on the tumour cell membranes. This labelling pattern showed no
      significant association with either the histological sub-type or stage of the
      carcinomas. Therefore, although distinct patterns of expression of MMP-2 and MT
      MMP1 were shown by these carcinomas, functional studies by means of zymography
      would be required to provide useful information on tumour behaviour.

PMID- 12056776
TI  - Clinicopathological and immunophenotypical features of canine intravascular
      lymphoma (malignant angioendotheliomatosis).
AB  - Intravascular lymphoma (IVL) is a rare angiotropic large-cell lymphoma in which
      neoplastic lymphocytes proliferate within the lumina of blood vessels in the
      absence of a primary extravascular mass or leukaemia. A retrospective review of
      veterinary medical records identified 17 cases of canine IVL. Spinal cord ataxia
      (seven dogs), posterior paralysis (one dog), seizures (four dogs) and vestibular
      disease (three dogs) dominated the clinical presentation. Haemorrhage, ischaemia,
      and occasional foci of vascular proliferation were found in tissue sections from
      affected dogs. Vessels, predominantly veins, throughout the body were frequently
      filled with neoplastic lymphocytes. Splenic involvement occurred in only one of
      10 cases examined and bone marrow involvement was absent in four cases examined.
      Formalin-fixed paraffin wax-embedded tissues from 15 cases were examined
      immunohistochemically with streptavidin-biotin-horseradish peroxidase and a
      catalysed signal amplification system. The neoplastic cells were classified in
      eight cases as T cells (CD3+/IgG-/CD79a-), in one case as B cells (CD3
      /CD79a.dim/IgG+), and in the remaining six cases as non-T, non-B (CD3-/IgG-/CD79a
      ). The clinical and pathological features of canine IVL closely resembled those
      of the human disease. In striking contrast to human cases, which are most often B
      cell lymphomas, the immunophenotypes of the canine IVLs in this series were
      heterogeneous. The canine IVLs were derived primarily from T cells and non-T, non
      B lymphocytes, B cells being found in only a single instance.

PMID- 12056777
TI  - Expression of chemokine receptors in the feline reproductive tract and large
      intestine.
AB  - Feline immunodeficiency virus (FIV) is a lentivirus that causes feline acquired
      immunodeficiency syndrome. Infection can be transmitted experimentally via the
      vagina and rectum, making the cat a useful model for human immunodeficiency virus
      (HIV) infection. Some strains of FIV use the CXCR4 chemokine receptor in vitro to
      gain entry to feline cell lines, thymocytes and peripheral blood leucocytes
      (PBLs). In this study, the tissue expression of messenger ribonucleic acid (mRNA)
      encoding the CCR3, CXCR4 and CCR5 receptors was examined by reverse transcriptase
      polymerase chain reaction (RT-PCR). mRNA encoding each receptor was expressed by
      two feline T-cell lines (Mya-1 and FeTJ), a feline kidney fibroblast cell line
      (FKCU) and PBLs. Mesenteric lymph node, colon, rectum, uterus, cervix and vagina
      all expressed mRNA for CXCR4 and CCR5 whilst only lymph node expressed CCR3 mRNA.
      In order to locate this receptor mRNA expression, in-situ hybridization studies
      were performed with DNA probes specific for the chemokine receptor mRNAs. CCR5
      and CXCR4 receptor mRNA was expressed by epithelial cells and some lamina propria
      cells of the colon and rectum. Epithelial cell expression of chemokine receptor
      mRNA was reduced in intensity towards the base of the crypts. Expression of CXCR4
      receptor was also demonstrated immunohistochemically on some lamina propria and
      intraepithelial cells. The expression of these receptor molecules may be
      important in mucosal infection with FIV.

PMID- 12056778
TI  - Juvenile parameningeal rhabdomyosarcoma in a dog causing unilateral denervation
      atrophy of masticatory muscles.
AB  - A 23-month-old, male, Labrador retriever dog with a history of slowly progressive
      right-sided atrophy of the masticatory muscles was submitted for necropsy. A
      highly invasive neoplasm which destroyed adjacent soft tissues including the
      right trigeminal nerve was found in the right side of the cranial cavity.
      Metastases to the liver were also present. Microscopical features of the neoplasm
      were compatible with those of rhabdomyosarcoma, embryonal type. This diagnosis
      was confirmed by immunohistochemical demonstration of desmin and muscle actin
      within tumour cells. In human patients, rhabdomyosarcoma is the most common soft
      tissue sarcoma of childhood and adolescence. Parameningeal rhabdomyosarcomas are
      well-known topographic variants that are often non-amenable to complete surgical
      resection and therefore carry a more guarded prognosis. Juvenile parameningeal
      rhabdomyosarcoma resulting in denervation atrophy of the muscles of mastication
      has not been reported previously in dogs. Rhabdomyosarcoma should be included in
      the differential diagnosis of neoplastic conditions in the head and neck region
      of juvenile dogs presented with cranial nerve palsies or other neurological
      deficits suggestive of meningeal or central nervous system invasion.

PMID- 12056779
TI  - Herpes simplex encephalitis in a domestic rabbit (Oryctolagus cuniculus).
AB  - An adult domestic rabbit showing neurological signs was subjected to euthanasia.
      At necropsy, macroscopical lesions were absent. Histopathologically, extensive
      lesions were seen, particularly in the cerebral cortex. Non-suppurative
      meningitis was present and there was lymphocytic and plasmacytic perivascular
      cuffing in the neuropil. The cerebral cortex showed extensive segmental neuronal
      and glial necrosis. Within the necrotic areas, large amphophilic intranuclear
      inclusion bodies were present in neurons and glial cells. Immunohistochemically,
      neurons and glial cells in the affected areas were labelled by polyclonal
      antibodies against both herpes simplex virus-1 (HSV-1) and HSV-2. The agent was
      classified as HSV-1 by polymerase chain reaction analysis. This is only the
      second reported natural case of herpes simplex infection in a rabbit.

PMID- 12056780
TI  - Borna disease in a dog in Japan.
AB  - Borna disease (BD) was diagnosed in a 3-year-old male Welsh corgi suffering from
      a severe and acute progressive disorder of the central nervous system.
      Histopathologically, neuronal lesions were characterized by a non-suppurative
      encephalomyelitis dominated by large perivascular cuffs consisting of
      lymphocytes, macrophages and plasma cells; also present were inflammatory cell
      infiltrates in the neural parenchyma, neuronophagia and focal gliosis. Strong
      immunolabelling with BD virus (BDV) p40 antibody was diffusely distributed in the
      cytoplasm of small and large neurons in areas of the brain with and without
      inflammatory changes, and also in the spinal cord. Positive hybridization signals
      with BDV p40 sense and antisense riboprobes were seen in the nucleus and
      cytoplasm of the neurons throughout the whole brain and spinal cord. BDV p24 RNA
      in formalin-fixed brain tissue was detected by reverse transcriptase (RT)-nested
      polymerase chain reaction (PCR). BDV p24 RNA-positive signals were detected in
      the temporal lobe. This is the first report of spontaneous canine BD in Japan.

PMID- 12056781
TI  - Percutaneous endoscopic gastrostomy and the evolution of contemporary long-term
      enteral access.
AB  - This paper is based on the opening lecture of the 23rd Congress of the European
      Society of Parenteral and Enteral Nutrition (ESPEN), given on September 9, 200l
      in Muenchen, Germany. The article relates the story of the origin and the
      evolution of the percutaneous endoscopic gastrostomy or PEG, based on the then
      novel concept of sutureless approximation of a hollow viscus to the abdominal
      wall. It also provides a perspective of the clinical applications of PEG, in
      general, and the author's pediatric experience in particular. Additionally, it
      briefly describes the old and new expanded applications of the PEG concept. In
      this communication, the author of the procedure encourages young investigators to
      ask relevant questions in research and in clinical settings aimed at developing
      new ideas and concepts in the field of nutrition. He also stresses the need to
      carefully reflect upon the ethical and moral implications of new discoveries. The
      article contains pertinent illustrations and bibliographic references.

PMID- 12056782
TI  - Differential effects of selective and non-selective NOS inhibition on renal
      arginine and protein metabolism during endotoxemia in rats.
AB  - BACKGROUND AND AIMS: The kidney is the main endogenous producer of circulating
      arginine. Renal arginine disposal is directed to protein synthesis, urea
      production and nitric oxide synthesis. The administration of nitric oxide
      synthase inhibitors during sepsis may be beneficial or detrimental depending on
      the specificity of the inhibitor. We aimed to measure the effects of two NOS
      inhibitors, with different specificity, on renal arginine and protein turnover in
      a rat model of sepsis. METHODS: Rats were subject to double hit endotoxemia and
      either L-NAME (non-specific), SMT (iNOS specific) or saline. Under anesthesia,
      vessels supplying and draining the kidney were catheterized. Systemic and intra
      renal arginine and protein metabolism were measured using a primed continuous
      infusion of L-[2,3-(3)H]arginine and L-[2,6-(3)H]phenylalanine. RESULTS: Non
      specific NOS reduced systemic protein and arginine turnover, whereas selective
      iNOS inhibition did not. In the kidney, blood flow was reduced by L-NAME, but not
      by SMT. In conjunction with this, non-selective NOS inhibition increased renal
      protein breakdown, whereas selective iNOS inhibition increased renal arginine
      production. CONCLUSIONS: This study shows that non-selective NOS inhibition using
      L-NAME is detrimental for systemic and renal protein metabolism. Selective NOS
      inhibition stimulates renal arginine synthesis, without changing circulating
      arginine levels.

PMID- 12056783
TI  - Usefulness of short-lived proteins as nutritional indicators surgical patients.
AB  - BACKGROUND AND AIMS: Biochemical indicators are used to assess the adequacy of
      nutritional support given to postoperative patients. However, the metabolic
      alterations present in these patients diminish the efficiency of these
      indicators. The objective of this work is to determine the usefulness of short
      lived proteins as indicators to assess the nutritional support administered to
      patients during the metabolic stress phase produced by surgery. METHODS: The
      nitrogen balance and plasma concentrations of transthyretin, retinol binding
      protein, and insulin-like growth factor-1 were determined in 24 patients who
      received 4 different nutritional regimens during 7 days after surgery. RESULTS:
      Transthyretin and retinol binding protein, although sensitive to nutritional
      intake (P<0.0005 and P<0.04 respectively), were strongly affected by the stress
      response (P<0.008 and P<0.0003 respectively), thus limiting their usefulness for
      nutrition assessment. Insulin-like growth factor-1 was not influenced by the
      stress response and was sensitive to the nutritional supply (P<0.0001). Insulin
      like growth factor-1 was the only component that showed similar efficiency than
      nitrogen balance as nutritional indicator. CONCLUSIONS: Transthyretin and retinol
      binding protein are not adequate to assess the nutritional supply during the
      stress phase after surgery, while insulin-like growth factor-1 is a suitable
      indicator of the adequacy of recent intake in this situation, similar in
      performance to nitrogen balance.

PMID- 12056784
TI  - Bio-electrical impedance spectroscopy: alternatives for the conventional hand-to
      foot measurements.
AB  - BACKGROUND AND AIMS: Bio-impedance spectroscopy (BIS) is a very attractive method
      for measuring body composition. The standard method measures impedance from hand
      to foot. However, in patients a hand or foot is not always accessible. In these
      cases alternative methods would be helpful. The objective of this study was to
      compare BIS measurements from hand to foot (HF) with foot to foot (FF) and hand
      to hand (HH) measurements as alternatives. Aims were firstly, to assess the
      relationship between resistance (R) values measured by the different methods,
      secondly, to study the influence of body geometry on this relationship and
      lastly, to assess the predictive capacity of the methods for measuring body fluid
      volumes. METHODS: In 53 subjects with different degrees of obesity (mean BMI =
      38; SD = 9 kg/m(2)) three BIS measurements were performed from HF, HH and FF with
      a Xitron 4000B machine. Resistances of extracellular (Recw) and intracellular
      water (Ricw) were extrapolated by fitting the data to a Cole-Cole plot. Total
      body water (TBW) and extracellular water (ECW) were measured by deuterium and
      bromide dilution respectively. Intracellular water (ICW) was calculated as TBW
      ECW. Anthropometric measurements, including length and circumference of limbs and
      trunk, were performed as measures for body geometry. RESULTS: The Recw, Ricw and
      R50 values of HF measurements could be accurately described as a function of the
      Recw, Ricw and R50 values of HH or FF measurements. The relative circumference of
      arms and legs and the length of the trunk influenced the relationship between R
      values of the three different measurements. The degree of overweight did not
      affect this relationship. The precision of the predictions of TBW, ECW and ICW
      based on R values of the HH measurements were comparable with the traditional HF
      measurements while the FF measurements gave slightly less accurate results.
      CONCLUSIONS: Under circumstances where total body BIS measurements cannot be
      performed, FF or HH measurements may be used as alternatives. However, for
      clinical use the effect of changes in fluid distribution on the accuracy of these
      methods needs to be studied further.

PMID- 12056785
TI  - The local vascular tolerance to an intravenous infusion of a concentrated
      glutamine solution in ICU patients.
AB  - BACKGROUND AND AIMS: The beneficial effects of glutamine is well-documented in
      ICU patients. However, the documentation and control of enteral administration of
      glutamine is still insufficient. As an adjunct to enteral nutrition, a
      concentrated dipeptide solution may be given in a central venous line, but
      administration via a peripheral vein would be preferable. Therefore, we
      systematically evaluated local vascular tolerance following a concentrated
      dipeptide infusion in ICU-patients. METHODS: ICU-patients (n=20) were randomized
      to receive a 20% alanyl-glutamine infusion of 0.5 g/kg or placebo during 4 h in a
      peripheral vein on 3 consecutive days. Local tolerance was evaluated clinically,
      by Maddox score, and ultrasonically before the infusion and on days 1, 4 and 8
      after the infusion. RESULTS: In the study, 56 out of 60 (93%) planned infusions
      were administered and 157 out of 168 (93%) clinical evaluations were successfully
      performed. The ultrasonic evaluation revealed that the utilized veins had a
      diameter of 2.15+/-0.8 mm (range, 1.0--4.4 mm). There were no signs of
      thrombophlebitis in any single vein. CONCLUSION: Administration of a glutamine
      containing dipeptide concentrate (20%) by peripheral veins is safe in terms of
      local tolerance, if a strict protocol is adapted for this purpose is used.

PMID- 12056786
TI  - Resting energy expenditure in young patients with cystic fibrosis receiving
      antibiotic therapy for acute respiratory exacerbations.
AB  - BACKGROUND: patients with cystic fibrosis commonly have severe malnutrition and
      growth retardation. Among possible causes of these manifestations are low caloric
      intake, loss of nutrients and increased resting energy expenditure. This study
      was designed to assess the influence of antibiotic therapy for infectious
      exacerbations on resting energy expenditure in young patients with cystic
      fibrosis. METHODS: We studied 17 patients with cystic fibrosis (mean age, 13.6
      years). All were hospitalized to receive intravenous antibiotic therapy (mean
      duration, 2 weeks) for acute respiratory exacerbations. At the beginning of
      therapy and after it ended, all patients underwent blood chemical tests,
      anthropometrical measures, determination of body composition by bioelectrical
      impedance, spirometry, and indirect calorimetry. RESULTS: Antibiotic therapy led
      to a significant improvement in biochemical, spirometric variables and in
      estimated calorimetry measurements expressed in relation to fat-free mass. These
      findings suggest that infective exacerbations are among the causes of increased
      resting energy expenditure in young patients with cystic fibrosis. CONCLUSIONS:
      Indirect calorimetry may prove useful in the diagnosis of infective exacerbations
      and in monitoring the effect of antibiotic therapy in patients with cystic
      fibrosis.

PMID- 12056787
TI  - Lack of effectiveness of short-term intravenous micronutrient nutrition in
      restoring plasma antioxidant status after surgery.
AB  - BACKGROUND AND AIMS: Many patients recovering from surgery may be in a state of
      negative antioxidant balance. For those whose postoperative nutritional
      requirements are provided intravenously, this may not be adequate for antioxidant
      repletion. This study was undertaken to assess the total antioxidant status of
      these patients peri-operatively and prior to beginning intravenous nutrition
      (IVN), and to determine the adequacy of IVN, including daily micronutrients, in
      maintaining or restoring antioxidant status in the post-operative period.
      METHODS: Plasma total antioxidant status (TAS) was measured in 30 patients who
      were fed by standard IVN following surgery. Additionally, the 'antioxidant gap'
      (AOG, a measure of the contribution of antioxidants other than albumin and urate)
      was calculated. Blood samples were taken on beginning IVN and daily for the
      duration of IVN, which lasted for up to 26 days. RESULTS: Prior to IVN, 20 of the
      30 patients had a plasma TAS below the reference range and 15 of these 20
      remained deficient even after IVN of up to 19 days. A further 3 patients became
      deficient whilst on IVN. When the group of patients who were deficient was
      compared with the group who were not, it was found that this difference was
      predominantly due to a difference in the AOG, (518 (115) v 709 (68) micromol/L
      (mean (SD)), P<0.0001). The groups did not differ in terms of age, C-reactive
      protein level, duration of IVN or daily thiol intake/Kg body weight. CONCLUSIONS:
      The difference in the gap antioxidants was thought to be due to their utilization
      in opposing the extra oxidative burden of surgery. Consideration of the
      antioxidant provision of standard IVN, principally the thiol-containing amino
      acids, ascorbate, alpha -tocopherol and trace elements suggests that this is
      insufficient to counter the sum of the pre-existing oxidative stress and the
      additional oxidative burden imposed by the surgery.

PMID- 12056788
TI  - Methionine-loading test: evaluation of adverse effects and safety in an
      epidemiological study.
AB  - BACKGROUND: Methionine loading test is commonly used to detect
      hyperhomocysteinemia in patients with arteriosclerosis and other conditions. As
      administration of methionine causes endothelial dysfunction in laboratory
      examinations, we explored whether loading with this compound leads to clinically
      relevant adverse effects, especially in vasculature. METHODS AND RESULTS: When
      studying genetic factors in arteriosclerosis we recorded acute complications
      during a standard methionine loading test (with a dose of 100 mg/kg bw) and
      assessed a 30-day mortality in a group of 296 patients with coronary artery or
      peripheral arterial disease and in 591 controls. Acute complications were
      observed in 33% of the women and 16.5% of the men. For each sex, the patients and
      controls exhibited the same proportion of complications. The most common symptom,
      dizziness, was attributable to methionine loading. In addition, isolated
      sleepiness, nausea, polyuria and decreased or increased blood pressure were
      observed in part of the subjects. None of the 887 individuals died within the 30
      day period following the test. CONCLUSION: Our study suggests that although
      standard loading with L-methionine frequently causes transitory complications
      impairing perception and vigilance, the test does not have serious adverse
      effects on vasculature and may be considered a safe procedure.

PMID- 12056789
TI  - Breast milk leptin: its relationship to maternal and infant adiposity.
AB  - BACKGROUND AND AIMS: Leptin, the product of the obese gene (ob), is synthesized
      by adipose tissue and contributes to the regulation of energy homeostasis and
      food intake. Recently, immunoreactive leptin was reported to be present in human
      milk. The objective was to determine if there was a relation between breast milk
      leptin concentrations and adiposity in exclusively breast-fed infants. METHODS:
      Fifty healthy, exclusively breast-fed infants beyond neonatal period, and their
      mothers were included into the study. Infants whose weight-for-length was above
      the 90th percentile were defined as obese (n=17), and non-obese if the weight for
      length between 20-90th percentile (n=33). Anthropometric measurements of infants
      and mothers were also made and breast milk samples were analyzed for leptin.
      RESULTS: There was no significant difference between breast milk leptin
      concentrations of obese and non-obese infants' mothers. Breast milk leptin
      concentrations were significantly correlated with mothers' body mass index when
      all subjects analyzed. There was no significant correlation between breast milk
      leptin concentrations and body mass index of infants. CONCLUSIONS: Leptin
      concentrations of human milk are not different in the mothers of obese and non
      obese infants. These findings suggests that milk-borne leptin has no significant
      effect on adiposity during infancy.

PMID- 12056790
TI  - The relationship between reduced vitamin antioxidant concentrations and the
      systemic inflammatory response in patients with common solid tumours.
AB  - BACKGROUND AND AIMS: The majority of patients with advanced cancer have reduced
      circulating concentrations of the vitamin antioxidants including retinol, alpha
      tocopherol and carotenoids. However, the basis of this reduction is not known.
      Vitamin antioxidant concentrations have been reported to be correlated with a
      systemic inflammatory response (as evidenced by C-reactive protein) in normal
      subjects and in patients with lung cancer. In order to determine whether this
      relationship was independent of tumour type patients other common solid tumours
      were studied. METHODS: Fasting circulating concentrations of vitamin antioxidants
      and C-reactive protein were measured in normal subjects (n=30) and patients with
      breast (n=15), prostate (n=15) and colorectal cancer (n=11). RESULTS:
      Concentrations of C-reactive protein were higher (P<0.0001) and vitamin
      antioxidants lower (P<0.0001) in the cancer patients. In normal subjects and
      cancer patients, C-reactive protein concentrations were inversely correlated with
      circulating concentrations of retinol (r(2)=0.162), alpha-tocopherol
      (r(2)=0.297), lutein (r(2)=0.256), lycopene (r(2)=-0.171), alpha-(r(2)=0.140) and
      beta-carotene (r(2)=0.254): (all P<0.001). CONCLUSIONS: Concentrations of
      retinol, alpha -tocopherol and carotenoids are inversely associated with the
      magnitude of the systemic inflammatory response. These relationships appear to be
      independent of the presence and type of cancer.

PMID- 12056791
TI  - Measured versus estimated energy expenditure in mechanically ventilated
      critically ill patients.
AB  - Accurate determination of energy expenditure is essential in patients receiving
      nutritional support to meet metabolic needs. The purpose of this study was to
      assess and compare the energy expenditure as measured by indirect calorimetry
      (MEE) and estimated by 5 equations in the mechanically ventilated critically ill
      patients. Forty-six patients were divided into either enteral nutrition (EN)
      (n=l2), total parenteral nutrition (TPN) (n=16) or combined (EN plus TPN) (n=l8)
      groups. Patients' energy expenditure was measured by indirect calorimetry on two
      occasions. Anthropometric and biochemical measurements, energy expenditure and
      medical status (APACHE II score) were also assessed in the intensive care unit
      (ICU) of Taichung Veteran General hospital. No significant difference was found
      in the MEE among the 3 groups. The type of nutritional support did not affect
      MEE. Energy expenditure calculated by using Harris- Benedict, Kleiber and Liu
      equations times the estimated stress factor did not significantly different than
      the values of MEE in all groups. There were significant correlations (P<0.01)
      between MEE and patients' sex (r=-0.499), age (r=-0.402), height (r=0.533), knee
      height (r=0.431), current body weight (r=0.379), usual body weight (r=0.407),
      ideal body weight (r=0.466) and urinary urea nitrogen (r=0.383) in the pooled
      group. Results demonstrated that energy expenditure could be estimated in most
      critically ill patients by using Harris-Benedict, Kleiber and Liu equations if
      the estimated stress factor is in the reasonable value.

PMID- 12056792
TI  - ESPEN guidelines on nutrition in acute pancreatitis. European Society of
      Parenteral and Enteral Nutrition.

PMID- 12056793
TI  - On the management of hyperemesis gravidarum.

PMID- 12056794
TI  - Age and sex influence on appetite.

PMID- 12056796
TI  - A conversation with Eugene Kennedy interview by K. Noelle Gracy.

PMID- 12056797
TI  - Innate form of HCV core protein plays an important role in the localization and
      the function of HCV core protein.
AB  - Hepatitis C Virus (HCV) has been identified as the major causative agent of non
      A, non-B hepatitis. Core protein is not only a capsid protein of HCV but also a
      regulator of cellular functions, and plays an important role in the pathogenesis
      of HCV. Core protein is produced as an innate form (amino acids [a.a.] 1-191),
      and following processing produces a mature form (a.a. 1-173). This study
      demonstrates that the innate form regulates subcellular localization of the
      mature form, and that the innate form in the cytoplasm enhances p21 expression;
      on the other hand, the mature form in the nucleus suppresses p21 expression.
      These observations suggest that the innate form is not only a precursor of the
      mature form but also a regulator of the localization and functions of core
      protein.

PMID- 12056798
TI  - Subcellular localization of HCV core protein regulates its ability for p53
      activation and p21 suppression.
AB  - Hepatitis C Virus (HCV) is a single stranded RNA virus causing non-A and non-B
      hepatitis. Core protein is a viral capsid protein that plays an important role in
      the pathogenesis of HCV. The companion report revealed that an innate form (amino
      acids [a.a.] 1-191) regulated subcellular localization of a mature form (a.a. 1
      173). It was also shown that the innate form in the cytoplasm enhanced the p21
      expression and the mature form in the nucleus suppressed the p21 expression. Here
      we report that the core protein in the cytoplasm increases the amount of p21 via
      activating p53, and the core protein in the nucleus decreases the amount of p21
      by the p53-independent pathway. These observations suggest that the regulation of
      p21 expression by the core protein via subcellular localization might decide the
      fate of infected cells either to the proliferation or to the apoptosis.

PMID- 12056799
TI  - Purification and characterization of a novel 7-kDa non-specific lipid transfer
      protein-2 from rice (Oryza sativa).
AB  - A novel 7-kDa non-specific lipid transfer protein-2 (nsLTP2) has been isolated
      from rice (Oryza sativa) seeds. In contrast to nsLTP1s, few nsLTP2s have been
      purified and characterized. Complete amino acid sequence of rice nsLTP2 was
      determined by N-terminal Edman degradation of the intact protein as well as the
      peptide fragments resulted from trypsin digestions. Rice nsLTP2 consists of 69
      amino acid residues with eight conserved cysteines forming four disulfide bonds.
      The secondary structure of rice nsLTP2 is predominantly alpha-helical as
      determined by circular dichroism spectroscopy. Cysteine pairings of nsLTP2 have
      one miss match at Cys(35)-X-Cys(37) motif compared to nsLTP1. Primary structure
      analysis of various plant nsLTP2s revealed an interesting conservation of
      sequence features among nsLTP2 family.

PMID- 12056800
TI  - Shear stress mediates tyrosylprotein sulfotransferase isoform shift in human
      endothelial cells.
AB  - In this study, we examined expression of tyrosylprotein sulfotransferase (TPST)
      isoforms TPST1 and TPST2 in primary cultures of human umbilical vein endothelial
      cells. For the first time coexpression of both isoforms is shown in primary human
      cells. Application of physiological levels of shear stress regulates expression
      of TPST isoforms in a time- and dose-dependent manner. Sustained application of
      arterial laminar shear stress causes downregulation of TPST1 mRNA and protein
      expression, while TPST2 is upregulated. This TPST isoform shift is mediated by
      different signaling pathways. Shear stress-dependent downregulation of TPST1
      involves tyrosine kinase, while upregulation of TPST2 is mediated by a protein
      kinase C-dependent pathway [corrected].

PMID- 12056801
TI  - Activation of PKC-beta isoforms mediates HNE-induced MCP-1 release by
      macrophages.
AB  - 4-Hydroxynonenal (HNE) in the concentration range detectable in many
      pathophysiologic conditions is able to modulate signal transduction cascades and
      gene expression. Here, we report the stimulating effect of 1 microM HNE on the
      release of the monocyte chemotactic protein-1 (MCP-1) by murine macrophages. MCP
      1-increased export following 1-h cell treatment with HNE proved to be comparable
      to that exerted by standard amounts of bacterial lipopolysaccharide (LPS).
      However, the key molecular event in HNE-induced secretion of MCP-1 appeared to be
      the increased activity of beta-PKC isoforms, which are recognized as playing a
      role in the regulation of cell protein transport and secretion. On the other
      hand, in LPS-stimulated cells, the delta isoform was seen to be involved and was
      probably related to LPS-mediated effects on MCP-1 expression and synthesis. In
      conclusion, HNE might interact with other pro-inflammatory stimuli, like LPS, in
      a concerted amplification of MCP-1 production and secretion.

PMID- 12056802
TI  - A fungal auxin antagonist, hypaphorine prevents the indole-3-acetic acid
      dependent irreversible inactivation of horseradish peroxidase: inhibition of
      Compound III-mediated formation of P-670.
AB  - Hypaphorine, an indolic alkaloid from an ectomycorrhizal fungus is a putative
      antagonist of indole-3-acetic acid (IAA) known to inhibit the effect of IAA in
      growing roots of Eucalyptus seedling. Previously we have used horseradish
      peroxidase-C (HRP) as a sensitive reporter of IAA-binding to the IAA-binding
      domain, and reported that hypaphorine specifically inhibits the HRP-catalyzed
      superoxide generation coupled to oxidation of IAA [Kawano et al., Biochem.
      Biophys. Res. Commun. 288]. Since binding of IAA to the auxin-binding domain is
      the key step required for IAA oxidation by HRP, it was assumed that the
      inhibitory effect of hypaphorine is due to its competitive binding to the auxin
      binding domain in HRP. Here, we obtained further evidence in support of our
      assumption that hypaphorine specifically inhibits binding of IAA to HRP. In this
      study, HRP arrested at the temporal inactive form known as Compound III was used
      as a sensitive indicator for binding of IAA to HRP. Addition of IAA to the
      preformed Compound III resulted in rapid decreases in absorption maxima at 415,
      545, and 578 nm characteristic to Compound III, and in turn a rapid increase in
      absorption maximum at 670 nm representing the formation of P-670, the
      irreversibly inactivated form of hemoproteins, was induced. In contrast, the IAA
      dependent irreversible inactivation of HRP was inhibited in the presence of
      hypaphorine. In addition, the mode of interaction between IAA and hypaphorine was
      determined to be competitive inhibition, further confirming that hypaphorine is
      an IAA antagonist which specifically compete with IAA in binding to the IAA
      binding site in plant peroxidases.

PMID- 12056804
TI  - Evidence for a wide occurrence of proton-translocating pyrophosphatase genes in
      parasitic and free-living protozoa.
AB  - Proton-translocating inorganic pyrophosphatases (H(+)-PPase, EC 3.6.1.1) are
      integral membrane proteins that have been extensively studied in higher plants,
      the photosynthetic bacterium Rhodospirillum rubrum and, more recently, in some
      human pathogenic protozoa. By using a PCR-based approach, fragments of genes
      coding for H(+)-PPases in a number of protists, both free-living and parasites of
      animals and plants, that belong to diverse taxonomic groups (trypanosomatids,
      ciliates, apicomplexans, euglenoids, amoeboid mycetozoa, heterokonts) have been
      isolated. The experimental procedure involved the use of degenerate
      oligonucleotides designed from protein domains conserved in H(+)-PPases from
      plants and bacteria. The PCR-amplified DNA fragments exhibited the characteristic
      genomic structure and codon usage of the corresponding protozoan group.
      Paralogous genes were found in some species suggesting the occurrence of protein
      isoforms. These results indicate that H(+)-PPases are more widely distributed
      among protozoa than previously thought.

PMID- 12056803
TI  - Identification of a novel Comamonas testosteroni gene encoding a steroid
      inducible extradiol dioxygenase.
AB  - Comamonas testosteroni is a Gram-negative bacterium that can grow on steroids and
      polycyclic aromatic hydrocarbons (PAH) as sole carbon and energy source. Complete
      mineralisation of these compounds is achieved through complex metabolic pathways
      comprising a set of inducible enzymes. Whereas the degradation pathways for PAHs
      have been intensively studied, patterns of enzymes leading to ring fissions of
      the steroid nucleus are unclear. Several intermediates of the steroid and PAH
      degradation pathways have similar structures therefore the question remains of
      whether both classes are substrates of different degradation routes or whether
      some catabolic enzymes function in both pathways. Interestingly, our studies
      reveal that testosterone simultaneously induces the expression of steroid- and
      PAH-catabolising enzymes in C. testosteroni. By cloning the gene, one of these
      testosterone-inducible proteins (TIP1) turned out to be biphenyl-2,3-diol-1,2
      dioxygenase. This enzyme has been described to convert 2,3-dihydroxybiphenyl into
      2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid in PAH degradation. The gene was
      found on a cluster encoding TIP1, three orfs, and another testosterone-inducible
      protein (TIP6) of unknown function. The deduced amino acid sequence of TIP1
      revealed that the enzyme contains 299 amino acids (34 kDa) and shares homologies
      to a variety of other extradiol dioxygenases. Based on the similar catechol
      moieties in PAH and steroid intermediates, together with its inducibility by
      testosterone, it is conceivable that TIP1 functions as a steroid extradiol
      dioxygenase to convert steroidal secocatechols into the disecoandrostanes. Our
      data suggest a role of the reported TIP1 protein in both the degradation pathways
      for steroids and aromatic hydrocarbons.

PMID- 12056805
TI  - Purification and characterization of a neurotoxin from the venom of Ophiophagus
      hannah (king cobra).
AB  - A neurotoxin, Oh9-1, from the venom of Ophiophagus hannah was isolated by a
      combination of ion-exchange chromatography and reverse phase HPLC. Amino acid
      sequence analysis revealed that Oh9-1 consists of 57 amino acids and eight
      cysteine residues. This protein was mainly constituted with beta-sheet as
      evidenced by CD spectrum. Oh9-1 inhibited carbachol-induced muscle contraction in
      an irreversible manner and the dose for achieving 50% inhibition was
      approximately fourfold that of alpha-bungarotoxin. Since the residues in alpha
      neurotoxins closely involve in the binding with acetylcholine receptors are not
      highly conserved in this toxin molecule, Oh9-1 represents a novel type of
      neurotoxin structurally distinct from alpha-neurotoxins.

PMID- 12056806
TI  - ARHGAP10, a novel human gene coding for a potentially cytoskeletal Rho-GTPase
      activating protein.
AB  - Rho-GTPase activating proteins (Rho-GAPs) are negative regulators of Rho-GTPase
      signaling pathways related to actin cytoskeleton dynamics, cell proliferation,
      and differentiation. We have identified a novel human gene, termed ARHGAP10, that
      codes for a 1957-aminoacid Rho-GAP, containing a PDZ, a PH, and a Rho-GAP domain.
      The cDNA is 7118 bp long and has an open reading frame of 5874 bp. A
      computational analysis located this gene on chromosome 10 band 10p12.32
      suggesting that it is composed of 25 exons. Northern analysis revealed that it is
      widely expressed, with high levels in brain and muscle. Real-time quantitative
      PCR analysis confirmed an increase in ARHGAP10 expression during differentiation
      of HL-60 cells with all-trans-retinoic acid and hematopoietic stem cells with
      erythropoietin, suggesting that this gene could play a role in normal
      hematopoiesis. The fact that this gene is highly expressed in muscle and brain,
      which are highly differentiated tissues, further supports the hypothesis that
      ARHGAP10 is important for cell differentiation.

PMID- 12056807
TI  - Identification of protein kinase CK2 as a potent kinase of Epstein-Barr virus
      latent membrane protein 1.
AB  - The C-terminus of latent membrane protein 1 (LMP1) can be phosphorylated in vivo.
      However, the protein kinase responsible for LMP1 phosphorylation has not yet been
      identified. In this study, GST fusion proteins containing the C-terminus of LMP1
      were generated and used as substrates to survey the kinases that phosphorylate
      LMP1. Among several purified protein kinases tested, only protein kinase CK2
      (CK2) could specifically phosphorylate LMP1. Using the in-gel kinase assay in the
      absence and presence of a selective CK2 inhibitor, 4,5,6,7
      tetrabromobenzotriazole, CK2 was determined to be the major kinase to
      phosphorylate LMP1 in lymphoma and epithelial cell lines. This is the first study
      to show that CK2 is a potent kinase to phosphorylate LMP1 in vitro.

PMID- 12056809
TI  - Activation of peroxisome proliferator-activated receptor gamma inhibits
      osteoprotegerin gene expression in human aortic smooth muscle cells.
AB  - Increasing evidence indicates an important role of PPAR gamma activation in
      modulating the development and progression of atherosclerosis, however, the
      mechanisms involved in these effects are not well understood since the PPAR gamma
      regulated genes in vascular smooth muscle cells (VSMC) are poorly defined. Here
      we reported that PPAR gamma ligands, GW7845, ciglitazone and troglitazone had the
      effect of inhibiting osteoprotegerin (OPG) expression in human aortic smooth
      muscle cells (HASMC). The effect of GW7845 and ciglitazone on OPG expression was
      completely abolished by GW9662, a PPAR gamma antagonist. Overexpression of PPAR
      gamma in HASMC by the infection of a PPAR gamma adenovirus dramatically decreased
      OPG expression. In addition, PPAR gamma activation inhibited OPG promoter
      activity. Taken together, our data suggest that OPG expression is a novel PPAR
      gamma target gene in VSMC and downregulation of OPG expression by PPAR gamma
      activation provides a new insight into the understanding of the role of PPAR
      gamma in atheroscelrosis and hypertension.

PMID- 12056808
TI  - Heat shock protein 60 elicits abnormal response in macrophages of diabetes-prone
      non-obese diabetic mice.
AB  - Heat shock protein 60 (hsp60) is a target antigen in autoimmune diabetes and
      injections of human hsp60 for tolerance induction were found to protect non-obese
      diabetic (NOD) mice, an animal model of human type 1 diabetes, from disease
      development. We tested whether innate immune cells of NOD mice exhibit an
      abnormal response to extracellular hsp60. Bone marrow derived macrophages (BMM)
      were grown from NOD, C57BL/6J, non-obese non-diabetic (NON) mice, and NOD-related
      congenic variants differing in the Idd-3, Idd-10/18, or major histocompatibility
      complex (MHC) region. Hsp60-stimulated BMM of NOD mice were found to produce high
      levels of interleukin (IL)-12(p70). The addition of IL-10 downregulated, whereas
      cyclooxygenase inhibitors elevated, IL-12(p70) production of activated BMM. BMM
      of NON, NON-NOD-H-2(g7) as well as of NOD-NON-H-2(nbl) mice produced
      significantly less IL-12(p70) than BMM of NOD mice, indicating that an
      interaction between the MHC haplotype and non-MHC genes of the NOD mouse is
      required for hyperresponsiveness to hsp60.

PMID- 12056810
TI  - WISP-2 is a secreted protein and can be a marker of estrogen exposure in MCF-7
      cells.
AB  - As many structurally diverse chemicals have been reported to function as
      estrogens, evaluations for estrogenicity of compounds are of widespread concern.
      Recently, we identified WISP-2 (Wnt-1 inducible signaling pathway protein 2) as a
      novel estrogen-inducible gene in human breast cancer cells. In this study, we
      examined whether WISP-2 could be utilized as a marker for screening
      environmentally relevant compounds for estrogenicity. In MCF-7 cells,
      progesterone, dexamethasone, tri-iodothyronine, and 2,3,7,8-tetrachlorodibenzo-p
      dioxin did not regulate the expression of WISP-2, indicating that its induction
      is highly specific for hormones that interact with the estrogen receptor. Western
      blot analysis detected WISP-2 protein induced by 17-beta-estradiol (E2), not only
      in the cell lysates but also in the culture supernatant of exposed cells,
      indicating that WISP-2 was a secreted protein. The induction of WISP-2 protein by
      E2 in the culture supernatant was dose-dependent with estimated EC(50) levels
      between 10 and 100 pM. Our results demonstrated the capacity to screen
      environmental compounds for estrogenicity via WISP-2 induction.

PMID- 12056811
TI  - Genomic organization, transcriptional mapping, and evolutionary implications of
      the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL).
AB  - Histidyl-tRNA synthetase catalyses the covalent ligation of histidine to its
      cognate tRNA as an early step in protein biosynthesis. In humans, the histidyl
      tRNA synthetase gene (HARS) is oriented opposite of a synthetase-like gene
      (HARSL) that bears striking homology to HARS. In this report, we describe the
      genomic organization of the HARS/HARSL locus and map multiple transcripts
      originating from a bi-directional promoter controlling the differential
      expression of these genes. The HARS and HARSL genes each contain 13 exons with
      strong structural and sequence homology over exons 3-12. HARS transcripts
      originate from two distinct promoters; a cluster of short transcripts map 15-65
      bp upstream of the HARS ORF while a single, longer transcript (352 bp 5(')-UTR)
      maps to a distal promoter. Similarly, multiple HARSL transcripts (mapping 10-198
      bp upstream of its ORF) are produced by the shared bi-directional promoter. Human
      and rodent HARS/HARSL loci are homologous and support a model of inverted gene
      duplication to explain the emergence of HARSL during mammalian evolution.

PMID- 12056812
TI  - Hypocretin stimulates [(35)S]GTP gamma S binding in Hcrtr 2-transfected cell
      lines and in brain homogenate.
AB  - In vitro functional analyses of hypocretin/orexin receptor systems were performed
      using [(125)I]hypocretin radioreceptor and hypocretin-stimulated [(35)S]GTP gamma
      S binding assay in cell lines expressing human or canine (wild-type and
      narcoleptic-mutation) hypocretin receptor 2 (Hcrtr 2). Hypocretin-2 stimulated
      [(35)S]GTP gamma S binding in human and canine Hcrtr 2 expressing cell lines,
      while cell lines expressing the mutated canine Hcrtr 2 did not exhibit specific
      binding for [(125)I]hypocretin or hypocretin-stimulated [(35)S]GTP gamma S. In
      rat brain homogenates, regional specific hypocretin-stimulated [(35)S]GTP gamma S
      binding was also observed. Hypocretin-stimulated [(35)S]GTP gamma S binding, may
      thus be a useful functional assay for hypocretin receptors in both cell lines and
      brain tissue homogenates.

PMID- 12056813
TI  - Secondary structural wobble: the limits of protein prediction accuracy.
AB  - At present, accuracies of secondary structural prediction scarcely go beyond 70
      75%. Secondary structural comparison is carried out among sequence-identified
      proteins. The results show natural wobble between different secondary structural
      types is possible in homologous families, and the best prediction accuracy will
      rarely be 100%. Besides shortcoming of the prediction approaches, secondary
      structural wobble is found to be responsible for nearly all secondary structural
      prediction limits. Only average 73.2% of amino acid residue is conserved in
      secondary structural types. The wobble allows alpha-class/coil and beta
      class/coil transitions but not direct alpha-class/beta-class transition.
      Propensity values representing the statistical occurrence of 20 amino acid
      residues in secondary structural wobbles are given.

PMID- 12056814
TI  - Modulation of gamma delta T cells in mouse buccal epithelium following antigen
      priming.
AB  - T cells using the gamma delta T cell receptor (TCR) are abundant in mucosal and
      epidermal tissues in mice. Most studies of mucosal gamma delta T cells, however,
      have examined cells from the intestinal mucosa, whereas little is known about the
      presence or function of gamma delta T cells in the oral cavity. To better
      understand the involvement of oral gamma delta T cells in immunity, we have
      characterized TCR variable gamma-gene usage in the buccal epithelium from normal
      mice, and from mice challenged locally with a non-replicating antigen (bovine
      serum albumin [BSA]) or by influenza-virus infection as a replicating antigen.
      Our findings demonstrate a restricted use of V gamma genes by buccal gamma delta
      T cells, consisting primarily of V gamma 1.2, V gamma 3, and V gamma 5, with
      minimal use of V gamma 2 and V gamma 4 genes. Of particular interest, 3-4 days
      post-antigen challenge with BSA, there was a precipitous drop in the level of
      expression of V gamma 1.2, V gamma 3, and V gamma 5 genes, and to a lesser extent
      for the V gamma 2 gene, whereas V gamma 4 gene expression increased between days
      1 and 2 post-priming. In influenza-infected mice, a similar pattern was observed
      for the V gamma 2 and V gamma 5 genes, but not other V gamma genes. The immune
      modulating effects of oral antigen exposure on buccal gamma delta T cells suggest
      that these cells are functionally involved in the local immune response to both
      replicating and non-replicating antigens in oral mucosal surfaces.

PMID- 12056815
TI  - Mouse aquaporin 10 gene (AQP10) is a pseudogene.
AB  - AQP10 is the newest member of aquaporins in mammals and expressed selectively in
      the duodenum and the jejunum in human functioning as aquaglyceroporin. Here we
      report the cloning of the mouse AQP10 gene. The gene is composed of six exons and
      spans 5.2 kb. The arrangement of the exons is well conserved between mouse and
      human. However, the initiator methionine is lost because of the mutation at the
      translation-initiation site. An insertion of four thymine residues in exon 2 and
      a deletion of a cytosine residue in exon 5 shift the reading frame. Moreover,
      aberrant exon/intron junction sequences of introns 2, 3, and 4 also shift the
      reading frame between exons. Genomic Southern blot revealed the mouse AQP10 gene
      as a single copy gene. The results indicate that the mouse AQP10 gene is a
      pseudogene. Furthermore, the mouse AQP10 transcript was not detected in the
      jejunum where the human AQP10 is strongly expressed.

PMID- 12056816
TI  - Analysis of gene expression profile in p130(Cas)-deficient fibroblasts.
AB  - p130(Cas) (Cas) is a docking protein that becomes tyrosine phosphorylated in v
      Src- or v-Crk-transformed cells and in integrin-stimulated cells. Cas -/-
      fibroblasts show defects in stress fiber formation, cell spreading, cell
      migration, and transformation by activated Src. To further characterize the role
      of Cas in signaling, we compared the expression profile in Cas -/- fibroblasts
      with that in Cas-re-expressing fibroblasts using the microarray methods. In Cas 
      /- fibroblasts, the expression of heme oxygenase 1 and caveolin-1 was reduced,
      but the expression of procollagen 1 alpha 1, procollagen 3 alpha 1, procollagen
      11 alpha 1, elastin, periostin, TSC-36, and MARCKS was enhanced. The domains in
      Cas necessary for the change varied among these genes. Activated Src reduced the
      expression of most of these genes both in Cas -/- and in Cas +/+ fibroblasts.
      These results suggest the existence of signaling pathways that emanate from Cas
      to gene expression.

PMID- 12056817
TI  - Activation of RET tyrosine kinase regulates interleukin-8 production by multiple
      signaling pathways.
AB  - Interleukin-8 (IL-8) is known to contribute to human cancer progression through
      its potential function as a mitogenic, angiogenic, or motogenic factor. We found
      a high level of IL-8 production in SK-N-MC human primitive neuroectodermal tumor
      cells transfected with the human RET gene (SK-N-MC (RET) cells) in response to
      glial cell line-derived neurotrophic factor (GDNF) stimulation. IL-8 was also
      produced at high levels in TT human medullary thyroid carcinoma and TPC-1 human
      papillary thyroid carcinoma cell lines both of which express activated RET
      tyrosine kinase. To investigate which signaling pathways are responsible for IL-8
      expression, we treated SK-N-MC (RET) cells with several kinase inhibitors before
      GDNF stimulation. The results showed that a MEK1 inhibitor, PD98059, a p38MAPK
      inhibitor, SB202190, and a protein kinase C (PKC) inhibitor, Calphostin C,
      markedly decreased the IL-8 secretion from SK-N-MC (RET) cells at 24 h after GDNF
      stimulation. In contrast, a phosphatidylinositol 3-kinase (PI3-K) inhibitor,
      LY294002, increased its secretion. These results thus suggested that IL-8
      production by RET tyrosine kinase is regulated by multiple signaling pathways.

PMID- 12056818
TI  - Identification of human L-fucose kinase amino acid sequence.
AB  - Fucose is a major component of complex carbohydrates. L-Fucose kinase
      (fucokinase) takes part in the salvage pathway for reutilization of fucose from
      the degradation of oligosaccharides. The amino acid sequence of human fucokinase
      was derived from a cDNA encoding a protein of hitherto unidentified function.
      Human fucokinase polypeptide chain consists of 990 amino acids with a predicted
      molecular mass of 107 kDa. The C-terminal part of its amino acid sequence showed
      sequence motifs typical for sugar kinases. Fucokinase full-length protein and a
      deletion mutant lacking the first 363 amino acids of the N-terminus were
      expressed in Escherichia coli BL21 cells. Both proteins displayed fucokinase
      activity. These results reveal that the discovered cDNA encodes the fucokinase
      protein and they confirm that a functional kinase domain is located in the C
      terminal part of the enzyme.

PMID- 12056819
TI  - The C-terminus of Gi family G-proteins as a determinant of 5-HT(1A) receptor
      coupling.
AB  - Using a universal signaling assay employing G-protein chimeras comprising the C
      terminal five amino acids of Gi1/2, Gi3, Go, and Gz fused to Gq, the calcium
      mobilizing G-protein, we explored the role of the C-terminus of Gi family G
      proteins as a determinant for 5-HT(1A) receptor functional coupling. Co
      expression of the 5-HT(1A) receptor with each of the Gq/Gi family chimeras
      resulted in a concentration-dependent increase in calcium upon addition of 5-HT,
      although the coupling efficiency differed dramatically. Gq/Gi3 resulted in the
      most efficient coupling based on both potency and relative maximum response to 5
      HT. Gq/Go also produced efficient coupling in terms of relative 5-HT efficacy
      (76% of the Gq/Gi3 maximum response), although 5-HT exhibited 4-fold lower
      agonist potency, and Gq/Gz and Gq/Gi1/2 conferred poor functional coupling.
      Agonist potencies and relative efficacies determined for a number of 5-HT(1A)
      receptor agonists using Gq/Gi3 coupling were significantly weaker than those
      described previously for coupling through the native G-protein. These results
      indicate the C-terminus of Gi3 as an important determinant for coupling to the 5
      HT(1A) receptor, while the reduced functional agonist activities suggest
      additional motifs participate in receptor/G-protein coupling.

PMID- 12056820
TI  - Histone deacetylase inhibition results in decreased macrophage CD9 expression.
AB  - Histone deacetylase (HDAC) inhibitors have been demonstrated to regulate myeloid
      cell differentiation. In the present study the effects of the HDAC inhibitor
      trichostatin A (TSA) on the tetraspanin cell surface antigen CD9 were determined
      in primary murine macrophages. TSA inhibited CD9 protein and message expression
      and was optimal by 48 h. TSA did not induce similar effects on other surface
      markers and resulted in a modest increase or no effect on CD54 and CD11b,
      respectively. These effects were concentration dependent and concomitant with
      increased histone H4 acetylation. While interferon-gamma (IFN-gamma) and TSA had
      similar effects on CD9 expression, transcriptional profiling demonstrated
      significant differences in the genes activated by these stimuli. Notably CD14
      message was down-regulated by IFN-gamma while increased by TSA. These results
      demonstrate that HDAC inhibition may modulate macrophage function in part through
      changes in the expression of membrane proteins associated with matrix
      interactions.

PMID- 12056821
TI  - Prolonged incubation in seawater induces a DNA-dependent protein phosphorylation
      activity in Arbacia punctulata eggs.
AB  - Various protein kinases are activated in eggs in response to fertilization. We
      have previously shown that the induction of DNA-dependent protein phosphorylation
      activity in the sea urchin eggs is triggered by fertilization. The present study
      demonstrates that the activation of a DNA-dependent serine/threonine kinase in
      unfertilized eggs of Arbacia punctulata can be achieved without fertilization.
      Prolonged incubation in seawater resulted in the activation of the eggs with
      concomitant induction of DNA-dependent protein phosphorylation activity. The
      activated eggs when fertilized show a slight increase in the phosphorylation
      activity 10-min post-insemination. The activity gradually declines as the first
      and second cleavages proceed. The cytoplasmic extracts of the blastulae,
      gastrulae, and plutei lack the enzyme activity. These findings reveal that not
      only fertilization but also egg activation serves as a signal for the induction
      of a DNA-dependent protein phosphorylation activity in sea urchin eggs suggesting
      that sperm-entry is not required for the induction of the enzyme activity.

PMID- 12056822
TI  - Upregulation of p21(WAF1/Cip1) precedes tumor necrosis factor-induced necrosis
      like cell death.
AB  - The molecular mechanisms mediating death receptor-induced caspase-independent
      necrotic cell death are still largely unknown. We have previously reported that
      NIH3T3 cells are sensitized by caspase inhibition to death receptor-induced
      cytotoxicity leading to a necrosis-like cell death. In addition, we have
      identified an important role of cell cycle progression for this sensitization
      effect. Here, we report that tumor necrosis factor-induced necrotic death is
      preceded by an upregulation of the cyclin-dependent kinase inhibitor
      p21(WAF1/Cip1). Increased expression of p21(WAF1/Cip1) occurs prior to cell death
      in the nucleus, where it binds to a cyclin-dependent kinase indicating its
      functionality. The use of specific pharmacological inhibitors revealed a partial
      involvement of p38 mitogen-activated protein kinase in the upregulation of
      p21(WAF1/Cip1). Inhibition of p21(WAF1/Cip1) upregulation prevents a previously
      observed delay of the cells in the G2/M phase of the cell cycle thereby
      augmenting, not inhibiting cell death.

PMID- 12056823
TI  - Secretion of MUC5AC mucin from pancreatic cancer cells in response to forskolin
      and VIP.
AB  - MUC5AC mucin is not expressed in normal pancreas but is expressed in tumors.
      Little is known about the mechanisms that lead to this atypical expression. In
      this study, we demonstrate that stimulation of adenylyl cyclase and the protein
      kinase A (PKA) pathway by forskolin and vasoactive intestinal peptide (VIP)
      increased MUC5AC antigen expression and release from pancreatic cancer cells.
      Stimulation of the PKA pathway also increased MUC5AC mRNA. When SW1990 pancreatic
      cancer cells were grown on porous membranes they released MUC5AC mucins apically
      in response to VIP (10(-7) M) applied to their basolateral surfaces. SW1990
      cells, as have been reported for other pancreatic cancer cells, have high
      affinity (<10(-7) M) VIP receptors and low affinity (>10(-6) M) secretin
      receptors. We also showed that four antibodies (CLH2, 21M1, 45M1, and Nd2) react
      with MUC5AC antigen in different cellular compartments of both tissues and
      cultured cells. In conclusion, the PKA pathway may contribute to the up
      regulation of MUC5AC expression seen in pancreatic tumors.

PMID- 12056824
TI  - Budding yeast Cdc5 phosphorylates Net1 and assists Cdc14 release from the
      nucleolus.
AB  - Polo-like kinase Cdc5 and Cdc14 phosphatase are essential for mitotic exit in
      budding yeast. Cdc14 sequestered in the nucleolus by forming a complex with Net1,
      a nucleolar inhibitor of Cdc14, is activated after the release from the nucleolus
      and Cdc5 is essential for this release. Here we show that Cdc5 affects the
      phosphorylation state of Net1. Tab6 is a dominant active form of Cdc14. We found
      that Tab6 was released from the nucleolus of cdc5 mutant cells in a cell cycle
      dependent manner and that the release of Tab6 (or Cdc14) was not sufficient for
      the cdc5 mutant to grow at a higher temperature. Altogether, we propose that Cdc5
      acts to reduce affinity between Cdc14 and Net1 and that the timing of Cdc14
      release is independent of Cdc5. We also provide evidence that the critical
      function of Cdc5, other than Cdc14 liberation, exists in late mitotic events.

PMID- 12056825
TI  - Physical association of beta 2 integrin with GPI-80, a novel
      glycosylphosphatidylinositol-anchored protein with potential for regulating
      adhesion and migration.
AB  - We recently found a novel GPI-anchored protein, GPI-80, on human phagocytes that
      may regulate leukocyte adherence, locomotion, and extravasation. To clarify the
      mechanisms by which GPI-80 functions on leukocytes, we explored the possibility
      of its physical association with beta 2 integrin which is important for leukocyte
      adherence, locomotion, and extravasation. beta 2 integrin, detected by anti-CD18
      mAb, was coprecipitated with GPI-80 from human neutrophil lysates by a mAb to GPI
      80. In addition, GPI-80 was immunoprecipitated from human neutrophil lysates by
      anti-human CD18 mAb. These results clearly show that GPI-80 is physically
      associated with beta 2 integrin in human neutrophils.

PMID- 12056826
TI  - Human recombinant stem cell factor promotes spermatogonial proliferation, but not
      meiosis initiation in organ culture of newt testis fragments.
AB  - We previously showed that mammalian FSH stimulates the proliferation of newt
      spermatogonia and induces their differentiation into primary spermatocytes in
      vitro. In the current study, to examine a possibility that stem cell factor (SCF)
      is involved in the proliferation of newt spermatogonia and/or their
      differentiation into primary spermatocytes, human recombinant SCF (rhSCF) was
      added to organ culture of testicular fragments. rhSCF was found to stimulate the
      spermatogonial proliferation and the spermatogonia progressed to the seventh
      generation that is the penultimate stage before primary spermatocyte stage.
      However, the spermatogonia did not differentiate into primary spermatocytes, but
      instead died of apoptosis. These results indicate that rhSCF promotes the
      proliferation of newt spermatogonia, but not the initiation of meiosis.

PMID- 12056827
TI  - Identification of a deubiquitinating enzyme subfamily as substrates of the von
      Hippel-Lindau tumor suppressor.
AB  - The VHL protein (pVHL) is a component of an E3 ubiquitin ligase complex which is
      involved in the ubiquitination and degradation of the alpha subunits of HIF
      (hypoxia-inducible factor) in the presence of oxygen. However, it is of
      considerable interest to identify pVHL substrates other than HIF. In our previous
      studies, we have shown that VDU1 (pVHL-interacting deubiquitinating enzyme-1) can
      be ubiquitinated for rapid degradation in a pVHL-dependent manner. In this report
      we show that another uncharacterized deubiquitinating enzyme, named VDU2 (pVHL
      interacting deubiquitinating enzyme-2), is a substrate of pVHL. Based on human
      and mouse cDNA sequences, VDU1 and VDU2 are identical in approximately 59% of the
      amino acids with strong homology in the N-terminus and C-terminus and a weaker
      similarity in the middle region. VDU2 contains the signature motifs of the
      ubiquitin-specific processing protease family and possesses deubiquitinating
      activity. Like VDU1, VDU2 interacts with pVHL beta-domain and these two proteins
      can compete with each other to bind to pVHL. Finally, we demonstrate that VDU2
      can also be ubiquitinated and degraded in a pVHL-dependent manner. Based on their
      amino acid sequence homology and functional interaction with pVHL, VDU1 and VDU2
      define a subfamily of ubiquitin specific processing proteases. Since
      deubiquitination, by reversing ubiquitination, has been recognized as an
      important regulatory step in ubiquitination-related processes, VDU1 and VDU2
      could be important substrates of pVHL E3 ligase complex.

PMID- 12056829
TI  - Overcoming the blockade at the upstream of caspase cascade in Fas-resistant HTLV
      I-infected T cells by cycloheximide.
AB  - In spite of carrying large amount of Fas death receptor on the cell surface,
      Human T cell lymphotropic virus type-I (HTLV-I)-infected T cell lines are
      resistant to Fas-mediated cytotoxicity. We investigated the mechanism(s) of HTLV
      I-induced Fas resistance. Western blotting and enzymatic activity analyses
      revealed that the Fas-elicited apoptotic signal in HTLV-I-infected T cells was
      intervened at the level(s) prior to the activation of caspase-8. Upon
      stimulation, the clustering of Fas receptors scarcely occurred in HTLV-I-infected
      cells. Cycloheximide treatment converted the resistant cells to sensitive cells;
      the presence of short-lived anti-apoptotic molecule(s) that can block the caspase
      8 activation within HTLV-I-infected T cells is suggested.

PMID- 12056828
TI  - Magnesium influx enhanced by nitric oxide in hypertensive rat proximal tubule
      cells.
AB  - An abnormal handling of renal magnesium has been suggested to cause salt
      sensitive hypertension. The filtered magnesium is first reabsorbed in the
      proximal tubule. Amiloride has been shown to enhance renal magnesium
      conservation, but the regulatory mechanisms are unknown yet. High-salt (8% NaCl)
      diet decreased serum magnesium concentration, while increased urinary magnesium
      in Dahl salt-sensitive (DS) rat. Furthermore, the expression of nitric oxide
      synthase type 3 and nitric oxide (NO) content were decreased in high-salt loaded
      DS rat. In isolated proximal tubule cells, amiloride (0.1 mM) increased
      intracellular free magnesium concentration ([Mg(2+)](i)). However, the net
      [Mg(2+)](i) increase in the high-salt loaded DS rat was smaller than other
      groups. NOR1 (0.1 mM), a NO donor, restored the increase of [Mg(2+)](i) to the
      same level of other groups. On the contrary, L-NMMA (0.1 mM), an inhibitor of NO
      production, inhibited the increase of [Mg(2+)](i) in all groups. These results
      suggest that intracellular NO has an important role to up-regulate amiloride
      elicited magnesium influx.

PMID- 12056830
TI  - Regulation of the type III InsP(3) receptor by InsP(3) and calcium.
AB  - It has been proposed that the inositol 1,4,5-trisphosphate receptor (InsP(3)R)
      type III acts as a trigger for InsP(3)-mediated calcium (Ca(2+)) signaling,
      because this InsP(3) isoform lacks feedback inhibition by cytosolic Ca(2+). We
      tested this hypothesis in RIN-m5F cells, which express predominantly the type III
      receptor. Extracellular ATP increases Ca(2+) in these cells, and we found that
      this effect is independent of extracellular Ca(2+) but is blocked by the InsP(3)R
      antagonist heparin. There was a dose-dependent increase in the number of cells
      responding to ATP and two-photon flash photolysis of caged-Ca(2+) heightened the
      sensitivity of RIN-m5F cells to this increase. These findings provide evidence
      that Ca(2+) increases the sensitivity of the InsP(3)R type III in intact cells
      and supports the idea that this isoform can act as a trigger for hormone-induced
      Ca(2+) signaling.

PMID- 12056831
TI  - Activation of Erk1/2 and Akt in astrocytes under ischemia.
AB  - Substantial evidence has shown that extracellular signal-regulated kinases 1 and
      2 (Erk1/2) and serine/threonine kinase (Akt) play important roles in regulating
      cell survival. We examined the activities of these kinases in astrocytes under
      ischemia in an anaerobic chamber. The level of phosphorylated Erk1/2 in
      astrocytes began to increase after 1 h ischemia, reached a maximum after 4 h
      ischemia, before decreasing from 5 to 6 h. Akt was activated later than Erk1/2.
      It was significantly increased after 4 h ischemia before declining steadily
      afterwards. Lactate dehydrogenase (LDH) assay and Hoechst nucleic staining
      indicated that U0126, which inhibits Erk1/2 phosphorylation, enhanced ischemia
      induced cell death, whereas LY294002, which inhibits Akt phosphorylation, delayed
      cell death. These effects were dose-dependent. At 4 and 6 h ischemia, U0126
      treated astrocytes expressed a lower level of Bcl-2 than controls. In contrast,
      LY294002-treated astrocytes expressed a higher level of Bcl-2 than controls as
      shown by Western blots. Bcl-x(L) expression level was not affected by either
      treatment. These data suggest that activation of the MAPK/Erk1/2 pathway might
      protect astrocytes from ischemic injury, but activation of the PI3-K/Akt pathway
      does not. The effect may involve Bcl-2 but not Bcl-x(L) expression.

PMID- 12056832
TI  - Head and neck cancer antigens recognized by the humoral immune system.
AB  - Head and neck cancer in advanced stages are difficult to treat. Therefore,
      development of new treatment modalities and preventive measures are required. We
      now report the identification of human head and neck cancer antigens recognized
      by the humoral immune system. We used the serological analysis of recombinant
      cDNA expression libraries (SEREX) approach. cDNA libraries from cell lines of
      squamous cell carcinoma of head and neck (SCCHN) and a normal testicle tissue
      were screened using sera from six allogeneic SCCHN patients. Total 28 positive
      clones belonging to 19 different genes were identified, including 12 known genes
      and 7 unknown ones. Expression analysis on 13 normal tissues and 13 cancer
      tissues using reverse transcription-PCR (RT-PCR) revealed eight ubiquitously
      expressed genes, nine of which were expressed preferentially in cancer tissues
      and two cancer/testis antigens. These antigens we defined may be pertinent
      candidate antigens for future cancer-diagnosis and related immunotherapy.

PMID- 12056833
TI  - Tenascins are associated with lipid rafts isolated from mouse brain.
AB  - Lipid rafts are microdomains of the plasma membrane which are enriched in
      glycosphingolipids and specific proteins. The reported interactions of several
      raft-associated proteins (such as, e.g., F3) with tenascin C and tenascin R
      prompted us to consider that these oligomeric multidomain glycoproteins of the
      extracellular matrix (ECM) could associate with rafts. Here, we show punctate
      immunocytochemical distributions of tenascin C (TN-C) and tenascin R (TN-R) at
      the membrane surface of neural cells resembling the pattern reported for raft
      associated proteins. Moreover, cholesterol depletion with methyl-beta
      cyclodextrin reduced the punctate surface staining of TN-C. Consistently, TN-C
      was associated with lipid rafts of neonatal mouse brain according to sucrose
      density gradient centrifugation experiments. Furthermore, TN-R was also found in
      rafts prepared from myelin of adult mice. Thus, brain-derived tenascins are able
      to associate with lipid rafts.

PMID- 12056836
TI  - Cyclin-dependent kinase-5/p35 phosphorylates Presenilin 1 to regulate carboxy
      terminal fragment stability.
AB  - Mutations in the Presenilin 1 gene are the cause of the majority of autosomal
      dominant familial forms of Alzheimer's disease. Presenilin 1 (PS1) is produced as
      a holoprotein but is then rapidly processed to amino- (N-PS1) and carboxy
      terminal (C-PS1) fragments that are incorporated into stable high molecular mass
      complexes. The mechanisms that control PS1 cleavage and stability are not
      properly understood but sequences within C-PS1 have been shown to regulate both
      of these properties. Here we demonstrate that cyclin dependent kinase-5/p35
      (cdk5/p35) phosphorylates PS1 on threonine(354) within C-PS1 both in vitro and in
      vivo. Threonine(354) phosphorylation functions to selectively stabilize C-PS1.
      Our results demonstrate that cdk5/p35 is a regulator of PS1 metabolism.

PMID- 12056835
TI  - NGF enhances sensory axon growth induced by laminin but not by the L1 cell
      adhesion molecule.
AB  - Neurotrophins and cell adhesion molecules regulate axon guidance, but their
      potential coordinate interactions are not well defined. In particular, it has
      been difficult to define the role of signaling from different surface molecules
      in neurotrophin-induced axon growth because of the strong dependence of embryonic
      neurons on this class of molecules for survival. We have addressed this issue
      using Bax deficient neurons, which do not require neurotrophins for survival. The
      L1 neural cell adhesion molecule and laminin each supported NGF-independent axon
      growth of cultured sensory neurons from dorsal root ganglia of embryonic Bax(-/-)
      mice. However, nerve growth factor (NGF) stimulated additional axon growth of
      sensory neurons on laminin but not on L1 substrates. Inhibition of the small
      GTPase RhoA by the dominant-negative mutant RhoA(T19N) restored NGF
      responsiveness of axon growth on L1 to Bax(-/-) neurons. Constitutively activated
      RhoA(Q63L) did not affect axon growth on L1 but inhibited NGF-stimulated axon
      growth on laminin. Consistent with the concept that RhoA was downregulated by NGF
      in neurons on laminin but not L1, the RhoA inhibitor C2IN-C3 toxin stimulated
      axon growth on L1 in wild-type DRG neurons in NGF. These results demonstrate a
      novel substrate-dependent regulation of NGF-induced growth of embryonic sensory
      axons mediated by RhoA GTPase.

PMID- 12056837
TI  - PTEN in neural precursor cells: regulation of migration, apoptosis, and
      proliferation.
AB  - PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas,
      macrocephaly, and mental deficiencies. We have used PTEN +/- mice to assess
      PTEN's role in subventricular zone (SVZ) precursor cells. For cultured SVZ
      neurosphere cells, haploinsufficiency for PTEN increases phosphorylation of Akt
      and forkhead transcription factor and slightly enhances proliferation. Based on a
      filter penetration assay, PTEN +/- cells are substantially more migratory and
      invasive than +/+ cells. The +/- cells also are more resistant to H(2)O(2)
      induced apoptosis. Analysis of PTEN +/- and +/+ mice by BrdU labeling reveals no
      difference in the rate of cell proliferation in the SVZ. Exit of BrdU-labeled
      cells from the SVZ and radial migration to the outer layers of the olfactory bulb
      are more rapid for +/- cells. These observations indicate that PTEN regulates SVZ
      precursor cell function and is particularly important for migration and apoptosis
      in response to oxidative stress.

PMID- 12056838
TI  - A2B5+ and O4+ Cycling progenitors in the adult forebrain white matter respond
      differentially to PDGF-AA, FGF-2, and IGF-1.
AB  - Cycling glial progenitors reside within subcortical white matter of the mammalian
      adult forebrain. Either A2B5 or O4 expression defines two of the major classes of
      cycling progenitors. We examined the growth factor receptor profiles of these
      progenitor populations and their capability to proliferate and differentiate in
      response to PDGF-AA, FGF-2, and IGF-1. FGF-2 and IGF-1 enhance the acquisition of
      O1 by the O4+ progenitors, but have no significant effect on the acquisition of
      O4 and/or O1 by the A2B5+ progenitors. In contrast, PDGF-AA enhances the
      acquisition of O1 by the A2B5+ progenitors, while having no significant affect on
      the acquisition of O1 by the O4+ progenitors unless combined with FGF-2. In
      addition, PDGF-AA and FGF-2 promote the proliferation of A2B5+ progenitors, while
      having no mitogenic effect on the O4+ progenitors unless the two factors are
      combined with IGF-1. Interestingly, not all of the progenitors within the A2B5 or
      O4 populations express the same growth factor receptors nor respond similarly to
      growth factors. Thus, there are substantial differences between the two
      populations and heterogeneity within each of these populations may exist.

PMID- 12056839
TI  - The axonal localization of large Drosophila ankyrin2 protein isoforms is
      essential for neuronal functionality.
AB  - In polarized cells, such as neurons, ankyrin-type proteins are the major
      molecules that link the actin-spectrin-based membrane cytoskeleton to the plasma
      membrane. In Drosophila the second ankyrin gene, Dank2, is exclusively expressed
      in neuronal cells. Similar to ankyrin genes in other organisms, the Dank2 gene
      generates several ankyrin protein isoforms by differential splicing. Here we
      report that in Drosophila, the short Dank2 protein isoform is restricted to
      neuronal cell bodies and is excluded from axons, whereas the long Dank2 isoforms
      are localized specifically to axons. Thus the long and short Dank2 protein
      isoforms are localized to complementary neuronal subdomains, demonstrating that
      in vivo the composition of the neuronal cortical cytoskeleton is highly
      polarized. We show that once polarization is established, it persists during
      later stages of Drosophila development. We also present genetic evidence that the
      absence of axonal Dank2 protein is lethal.

PMID- 12056840
TI  - Extracellular calcium controls the dynamic range of neuronal metabotropic
      glutamate receptor responses.
AB  - The metabotropicglutamate receptors (mGluRs) are neurotransmitter receptors
      important for synaptic plasticity in the brain. Here we report that native mGluR
      mediated neuronal responses to glutamate are profoundly modulated by
      extracellular calcium (Ca2+(o)). In mouse cerebellar Purkinje cells (PCs),
      Ca2+(o) drastically broadened the effective dose range for glutamate analogs in
      which native mGluR1-mediated cation current and intracellular Ca2+ mobilization
      were evoked. This effect has not been observed for recombinant mGluRs expressed
      in the heterologous cell systems. Ca2+(o) also drastically augmented these native
      mGluR-mediated responses to the glutamate analog. These Ca2+(o) effects were
      observed in both the wild-type mice and the mutant mice expressing mGluR1
      specifically in their PCs, suggesting that the native mGluR1 in the PCs but not
      those in other cell types are the key mediators of the effects. These findings
      demonstrate that Ca2+(o) plays an important role in regulating native mGluR
      mediated neuronal responses.

PMID- 12056841
TI  - Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar
      tissue in the lesioned spinal cord.
AB  - Transforming growth factor-betas (TGFbetas) are implicated in fibrotic
      pathologies. TGFbeta1 and -beta2 expression is increased around the
      glial/fibrotic scar in the injured brain. Moreover, local injection of TGFbeta
      antagonists into cerebral wounds reduces glial scarring. Here, we monitored
      expression of TGFbeta1 and -beta2 mRNA and protein in the spinal cord after
      transection of the dorsal funiculi. Levels of TGFbeta1 mRNA were most elevated
      over the acute inflammatory phase, while TGFbeta2 mRNA levels were raised locally
      about the wound, particularly in astrocytes and neovascular endothelial cells,
      over the subacute period of scarring. TGFbeta protein production also increased
      after injury. Both TGFbeta1 and TGFbeta2 were found in hematogenous inflammatory
      cells, while TGFbeta1 was also neuron-associated, and high levels of TGFbeta2
      were localized to multiple cell types in the wound, including reactive
      astrocytes, during the period of glial/collagen scar formation. The cellular
      localization and temporal pattern of expression of TGFbeta after spinal cord
      injury suggest that TGFbeta1 modulates the inflammatory and neuronal responses,
      while TGFbeta2 regulates glial/collagen scarring.

PMID- 12056843
TI  - Native and cloned 5-HT(3A)(S) receptors are anchored to F-actin in clonal cells
      and neurons.
AB  - Using selective antibodies to visualize the short isoform of the 5-HT(3A)
      receptor, we report here that both native and cloned 5-HT(3A)(S) receptors formed
      clusters associated with F-actin in all cell types studied. NG 108-15 cells
      expressing native 5-HT(3A)(S) receptors, COS-7 cells transiently expressing 5
      HT(3A)(S) subunits, and CHO cells stably transfected with a plasmid encoding the
      5-HT(3A)(S) sequence all exhibited similar surface receptor topology with 5
      HT(3A)(S) receptor cluster accumulation in F-actin-rich lamellipodia and
      microspikes. Colocalization and coclustering of 5-HT(3A)(S) subunits and F-actin
      were also observed in transfected hippocampal neurons. Treatment of the neurons
      with latrunculin-A, a compound altering F-actin polymerization, demonstrated that
      5-HT(3A)(S) receptor cluster size and topology were dependent on F-actin
      integrity. These results suggest that the anchoring of 5-HT(3A)(S) receptor
      clusters to the cytoskeletal network probably plays a key role in the
      physiological regulation of the receptor topology and dynamics, as is the case
      for other members of the 4-TMD ion channel receptor family.

PMID- 12056842
TI  - Identification of the regulatory region of the peripheral myelin protein 22
      (PMP22) gene that directs temporal and spatial expression in development and
      regeneration of peripheral nerves.
AB  - Minor changes in PMP22 gene dosage have profound effects on the development and
      maintenance of peripheral nerves. This is evident from the genetic disease
      mechanisms in Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary
      neuropathy with liability to pressure palsies (HNPP) as well as transgenic
      animals with altered PMP22 gene dosage. Thus, regulation of PMP22 is a crucial
      aspect in understanding the function of this protein in health and disease. In
      this study, we have generated transgenic mice containing 10 kb of the 5'-flanking
      region of the PMP22 gene, including the two previously identified alternative
      promoters, fused to a lacZ reporter gene. We show that this part of the PMP22
      gene contains the necessary information to mirror the endogenous expression
      pattern in peripheral nerves during development and regeneration and in mouse
      models of demyelination due to genetic lesions. Transgene expression is strongly
      regulated during myelination, demyelination, and remyelination in Schwann cells,
      demonstrating the crucial influence of neuron-Schwann cell interactions in the
      regulation of PMP22. In addition, the region of the PMP22 gene present on this
      transgene confers also neuronal expression in sensory and motor neurons. These
      results provide the crucial basis for further dissection of the elements that
      direct the temporal and spatial regulation of the PMP22 gene and to elucidate the
      molecular basis of the master program regulating peripheral nerve myelination.

PMID- 12056844
TI  - Inhibition of axon growth by oligodendrocyte precursor cells.
AB  - The glial scar that forms at the site of injury is thought to be a biochemical
      and physical barrier to successful regeneration, although the molecules
      responsible for this barrier function are not well understood. Glia scars contain
      large numbers of oligodendrocyte precursor cells (OPCs) and these cells can
      produce several different growth-inhibitory chondroitin sulfate proteoglycans
      (CSPGs), including NG2, neurocan, and phosphacan. Here, we used membrane-based
      assays to show that the surface of OPCs is both nonpermissive and inhibitory for
      neurite outgrowth. Inhibition of growth by OPC is reversed by treatment with
      antibodies against the NG2 CSPG and the expression of NG2 is sufficient to change
      a growth-permissive cell surface to a nonpermissive surface. These result suggest
      that the OPCs that accumulate rapidly at sites of CNS injury can contribute to
      the creation of an environment that inhibits nerve regeneration and that NG2 is a
      necessary feature of that environment.

PMID- 12056845
TI  - Microcontact printing: a versatile technique for the study of synaptogenic
      molecules.
AB  - During synaptogenesis information exchanged locally between synaptic partners
      results in precise alignment of morphological and molecular specializations. For
      example, agrin derived from motoneurons induces localized postsynaptic
      differentiation at the neuromuscular synapse. Similar information molecules are
      thought to act at other synapses; however, techniques for directly evaluating
      synaptogenic activities of such molecules are lacking. Here we use agrin-induced
      differentiation as a model system to validate a novel approach for characterizing
      synaptogenic molecules. Proteins are patterned with micron scale resolution on
      glass coverslips by covalent microcontact printing and these substrates are used
      for cell culture. Postsynaptic molecules accumulate specifically at sites of
      contact between muscle cells and patterned agrin: a response which is
      quantifiable. Our results demonstrate that microcontact printing is applicable to
      the analysis of cellular response to locally immobilized information molecules.

PMID- 12056846
TI  - beta-Neuregulin and autocrine mediated survival of Schwann cells requires
      activity of Ets family transcription factors.
AB  - Members of the Ets transcription factor family function in many biological
      processes. We show the presence of Ets transcription factors, most prominently
      Net, in neonatal rat Schwann cells, and demonstrate Ets-dependent transcription
      under conditions where the cells are exposed to autocrine signals or autocrine
      signals plus beta-neuregulin. Using the potent MAPK kinase inhibitor U0126 we
      also confirm that the MAP kinase pathway, an activator of Ets transcription, is
      involved in beta-neuregulin mediated Schwann cell survival. Furthermore, we find
      that expression of dominant negative Ets1 (N70-Ets1) inhibits both the beta
      neuregulin and autocrine survival of Schwann cells. In contrast, the survival of
      Schwann cells mediated by lysophosphatidic acid (LPA) is unaffected by expression
      of a dominant negative Ets molecule. These data demonstrate that distinct
      autocrine and beta-neuregulin survival signals converge in their requirement for
      Ets dependent transcription in Schwann cell survival.

PMID- 12056848
TI  - Articular cartilage repair: basic science and clinical progress. A review of the
      current status and prospects.
AB  - OBJECTIVE: To review the basic scientific status of repair in articular cartilage
      tissue and to assess the efficiency of current clinical therapies instigated for
      the treatment of structural lesions generated therein as a result of trauma or
      during the course of various diseases, notably osteoarthritis (OA). Current
      scientific trends and possible directions for the future will also be discussed.
      DESIGN: A systematic and critical analysis is undertaken, beginning with a
      description of the spontaneous repair responses in different types of lesion.
      Surgical interventions aimed at inducing repair without the use of active
      biologics will then be considered, followed by those involving active biologics
      and those drawing on autogenic and allogeneic tissue transplantation principles.
      Cell transplantation approaches, in particular novel tissue engineering concepts,
      will be critically presented. These will include growth-factor-based biological
      treatments and gene transfection protocols. A number of technical problems
      associated with repair interventions, such as tissue integration, tissue
      retention and the role of mechanical factors, will also be analysed. RESULTS: A
      critical analysis of the literature reveals the existence of many novel and very
      promising biologically-based approaches for the induction of articular cartilage
      repair, the vast majority of which are still at an experimental phase of
      development. But prospective, double-blinded clinical trials comparing currently
      practiced surgical treatments have, unfortunately, not been undertaken.
      CONCLUSION: The existence of many new and encouraging biological approaches to
      cartilage repair justifies the future investment of time and money in this
      research area, particularly given the extremely high socio-economic importance of
      such therapeutic strategies in the prevention and treatment of these common joint
      diseases and traumas. Clinical epidemiological and prospective trials are,
      moreover, urgently needed for an objective, scientific appraisal of current
      therapies and future novel approaches.

PMID- 12056849
TI  - Ultrastructural localization of type VI collagen in normal adult and
      osteoarthritic human articular cartilage.
AB  - OBJECTIVE: Type VI collagen is a major component of the pericellular matrix
      compartment in articular cartilage and shows severe alterations in osteoarthritic
      cartilage degeneration. In this study, we analysed the exact localization of type
      VI collagen in its relationship to the chondrocyte and the (inter)territorial
      cartilage matrix. Additionally, we were interested in its ultrastructural
      appearance in normal and osteoarthritic cartilage. DESIGN: Distribution and
      molecular appearance was investigated by conventional immunostaining, by
      multilabeling confocal scanning microscopy, conventional transmission, and
      immunoelectron microscopy. RESULTS: Our analysis confirmed the pericellular
      concentration of type VI collagen in normal and degenerated cartilage. Type VI
      collagen formed an interface in between the cell surface and the type II collagen
      network. The type VI collagen and the type II collagen networks appeared to have
      a slight physical overlap in both normal and diseased cartilage. Additionally,
      some epitope staining was observed in the cell-associated interterritorial
      cartilage matrix, which did not appear to have an immediate relation to the type
      II collagen fibrillar network as evaluated by immunoelectron microscopy. In
      osteoarthritic cartilage, significant differences were found compared with normal
      articular cartilage: the overall dimension of the lacunar volume increased, and a
      significantly increased type VI collagen epitope staining was observed in the
      interterritorial cartilage matrix. Also, the banded isoform of type VI collagen
      was found around many chondrocytes. CONCLUSIONS: Our study confirms the close
      association of type VI collagen with both, the chondrocyte cell surface and the
      territorial cartilage matrix. They show severe alterations in type VI collagen
      distribution and appearance in osteoarthritic cartilage. Our immunohistochemical
      and ultrastructural data are compatible with two ways of degradation of type VI
      collagen in osteoarthritic cartilage: (1) the pathologically increased
      physiological molecular degradation leading to the complete loss of type VI
      collagen filaments from the pericellular chondrocyte matrix and (2) the
      transformation of the fine filaments to the band-like form of type VI collagen.
      Both might implicate a significant loss of function of the pericellular
      microenvironment in osteoarthritic cartilage.

PMID- 12056850
TI  - Effects of SKI 306X, a new herbal agent, on proteoglycan degradation in cartilage
      explant culture and collagenase-induced rabbit osteoarthritis model.
AB  - OBJECTIVE: Protective effects of SKI 306X, a natural herbal product extracted
      from three herbs Clematis mandshurica, Trichosanthes kirilowii, and Prunella
      vulgaris, on articular cartilage was examined and compared with other
      osteoarthritis (OA) drugs using in vitro and in vivo models. METHODS: In vitro
      culture of rabbit articular cartilage explants was used as a model to measure the
      effects of drugs on the matrix degradation. The recombinant human interleukin
      1alpha (rhIL-1alpha, 5 ng/ml) was added to induce proteoglycan (PG) degradation
      and the degree of PG degradation was assessed by measuring the amount of
      glycosaminoglycan (GAG) released into the culture medium. In in vivo experiment,
      collagenase was intraarticularly injected twice into the right knee joint of
      rabbits to induce OA-like change, and test agents were orally administered once a
      day for 28 days. The degrees of OA-like changes were evaluated through a
      histological examination. RESULTS: In vitro study revealed SKI 306X inhibited the
      degradation of PG in a concentration-dependent manner. Trichosanthes kirilowii,
      which is one of the major components of SKI 306X, also significantly inhibited
      the GAG release in cartilage explant culture at 0.3 and 0.1 mg/ml. Dexamethasone
      and NSAIDs, such as diclofenac and rofecoxib, had no significant effects on the
      suppression of PG degradation. In in vivo studies, OA-like degeneration of the
      articular cartilage and synovial tissue was induced by injecting collagenase into
      the right knee joint of mature rabbits. At a dose of 200 mg/kg, SKI 306X reduced
      the OA-like histological changes, whereas diclofenac had no effect at 10 mg/kg.
      CONCLUSION: These results indicate that SKI 306X inhibited PG degradation in
      cartilage explant culture, and its prophylactic administration significantly
      protected the knee joint of rabbit from OA-like change in collagenase-induced
      experimental OA model. This strongly suggests that SKI 306X can be a good OA
      agent with some cartilage protection activity.

PMID- 12056851
TI  - Clinical evaluation of the WOMAC 3.0 OA Index in numeric rating scale format
      using a computerized touch screen version.
AB  - BACKGROUND: The Western Ontario and McMaster Universities (WOMAC) Osteoarthritis
      Index is a previously described self-administered questionnaire covering three
      domains: pain, stiffness and function. It has been validated in patients with
      osteoarthritis (OA) of the hip or knee in a paper-based format. AIM: To validate
      the WOMAC 3.0 using a numerical rating scale in a computerized touch screen
      format allowing immediate evaluation of the questionnaire. In the computed
      version cartoons, written and audio instruments were included in order facilitate
      application. METHODS: Fifty patients, demographically balanced, with
      radiographically proven primary hip or knee OA completed the classical paper and
      the new computerized WOMAC version. Subjects were randomized either to paper
      format or computerized format first to balance possible order effects. RESULTS:
      The intra-class correlation coefficients for pain, stiffness and function values
      were 0.915, 0.745 and 0.940, respectively. The Spearman correlation coefficients
      for pain, stiffness and function were 0.88, 0.77 and 0.87, respectively.
      CONCLUSION: These data indicate that the computerized WOMAC OA index 3.0 is
      comparable to the paper WOMAC in all three dimensions. The computerized version
      would allow physicians to get an immediate result and if present a direct
      comparison with a previous exam.

PMID- 12056852
TI  - Developmental and TGF-beta-mediated regulation of Ank mRNA expression in
      cartilage and bone.
AB  - OBJECTIVES: Ank encodes a transmembrane protein that is involved in pyrophosphate
      (PPi) transport and mutations in the Ank gene have been associated with
      pathological mineralization in cartilage and bone. To understand how Ank works in
      normal skeletal development it is also important to know which cells within the
      developing skeleton express Ank. To this end, we examined the expression pattern
      of Ank mRNA during mouse embryonic development as well as in mouse hind limb
      joints with emphasis on the period when articular cartilage forms. Since it was
      previously shown that TGF-beta regulates PPi transport in cells in culture, we
      also tested the hypothesis that TGF-beta regulates Ank expression. METHODS: The
      localization of Ank mRNA was determined by radioactive in situ hybridization in
      E15.5 and E17.5 mouse embryos as well as in 1 and 3 week post-natal mice. Ank
      expression was compared to that of other cartilage markers. In situ hybridization
      and semi-quantitative RT-PCR were used to determine the effects of TGF-beta on
      Ank expression in metatarsal organ cultures. RESULTS: Ank expression was detected
      at high levels at sites of both endochondral and intramembranous bone
      development. In endochondral bones, expression was detected in a subset of
      hypertrophic cells at ossification centers. Expression was also detected in
      osteogenic/chondrogenic cells of the perichondrium/periosteum lining the
      metaphysis, an area associated with the formation and extension of the bone
      collar. High levels of expression were also detected in non-mineralized tissues
      of the skeletal system including tendons and the superficial layer of the
      articular cartilage. Treatment with TGF-beta resulted in an approximately four
      fold induction of Ank mRNA in prehypertrophic chondrocytes and perichondrium of
      metatarsal cultures. CONCLUSIONS: The expression pattern of Ank suggests an
      important role both in inhibiting and regulating mineralization in the developing
      skeletal system. In addition, TGF-beta1 is able to mediate Ank mRNA expression in
      chondrocytes suggesting a possible role for TGF-beta and Ank in the regulation of
      normal mineralization.

PMID- 12056853
TI  - Can altered production of interleukin-1beta, interleukin-6, transforming growth
      factor-beta and prostaglandin E(2) by isolated human subchondral osteoblasts
      identify two subgroups of osteoarthritic patients.
AB  - OBJECTIVE: To determine the capacity of human subchondral osteoarthritic
      osteoblasts (Ob) to produce interleukin (IL)-1beta, IL-6, transforming growth
      factor-beta (TGF-beta) and prostaglandin E(2) (PGE(2)), and determine if a
      relationship exists between IL-1beta, TGF-beta, PGE(2) and IL-6 production.
      METHODS: We measured the abundance of IL-1beta, IL-6, TGF-beta and PGE(2) using
      very sensitive ELISA in conditioned-media of human primary subchondral Ob from
      normal individuals and osteoarthritic patients. Selective inhibition of IL-6 or
      IL-6 receptor signaling was performed to determine its effect on PGE(2)
      production whereas the inhibiton of PGE(2) production was performed to determine
      its effect on IL-6 production. The expression of bone cell markers and urokinase
      plasminogen activator (uPA) activity was also determined. RESULTS: Osteoarthritic
      Ob produced all these factors with greater variability than normal cells.
      Interestingly, the production of IL-6 and PGE(2) by osteoarthritic Ob separated
      patients into two subgroups, those whose Ob produced levels comparable to normal
      (low producers) and those whose Ob produced higher levels (high producers). In
      those cells classified as high osteoarthritic Ob, PGE(2) and IL-6 levels were
      increased two- to three-fold and five- to six-fold, respectively, compared with
      normal. In contrast, while using their IL-6 and PGE(2) production to separate
      osteoarthritic Ob into low and high producers, we found that IL-1beta levels were
      similar in normal and all osteoarthritic Ob. Using the same criteria, TGF-beta
      levels were increased in all osteoarthritic Ob compared with normal. Reducing
      PGE(2) synthesis by Indomethacin [a cyclo-oxygenase (COX) -1 and -2 inhibitor]
      reduced IL-6 levels in all osteoarthritic Ob, whereas Naproxen (a more selective
      COX-2 inhbitor) reduced PGE(2) and IL-6 levels only in the high osteoarthritic
      group. Conversely, PGE(2) addition to osteoarthritic Ob enhanced IL-6 production
      in both groups. Moreover, the addition of parathyroid hormone also stimulated IL
      6 production to similar normal levels in both osteoarthritic groups. In contrast,
      using an antibody against IL-6 or IL-6 receptors did not reduce PGE(2) levels in
      either group. The evaluation of alkaline phosphatase activity, osteocalcin
      release, collagen type I and uPA activity in osteoarthritic Ob failed to show any
      differences between these cells regardless to which subgroup they were assigned.
      CONCLUSIONS: These results indicate that IL-6 and PGE(2) production by
      subchondral Ob can discriminate two subgroups of osteoarthritic patients that
      cannot otherwise be separated by their expression of cell markers, and that
      endogenous PGE(2) levels influence IL-6 synthesis in osteoarthritic Ob.

PMID- 12056854
TI  - Cardiomyocyte resistance to doxorubicin mediated by A(3) adenosine receptor.
AB  - Recently, we reported that the activation of A(3) adenosine receptor (A(3)R) in
      newborn cultured cardiomyocytes by highly selective agonist Cl-IB-MECA (2-chloro
      N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide) induces protection against the
      anthracycline antibiotic doxorubicin (DOX) cardiotoxicity. The present study was
      undertaken to further characterize the cardioprotective action of A(3)R
      activation by revealing the structural changes in cardiomyocytes elicited upon
      exposure to DOX. Morphological observations (ultrastructural and
      immunocytochemical) indicate that after DOX treatment, the cardiomyocytes undergo
      destructive alterations, and protective action of A(3)R is not connected with its
      anti-apoptotic activity. A(3)R activation appeared to prevent destructive
      alterations of cardiomyocyte mitochondria and dissipation of mitochondrial
      membrane potential. In DOX-treated cardiomyocytes, appearance of disorganized
      desmin and contractile filaments was related to detrimental alterations in the
      mitochondrial structure, in particular their position and transmembrane
      potential. In intact cardiomyocytes, diazoxide, a selective mitochondrial K(ATP)
      channel opener, induced an increase in ATP synthesis within 15 min of
      application. Similar effect was obtained by activation of adenosine A(1)R.
      However, A(3)R agonist Cl-IB-MECA did not affect ATP synthesis. Neither A(1)R
      agonist CCPA (2-chloro-N(6)-cyclopentyladenosine) nor diazoxide protected
      cardiomyocytes from the detrimental effects of DOX. Thus, the opening of
      mitochondrial K(ATP) channels does not seem to be effective during the slow
      development of anthracycline cytotoxicity. Our results indicate that DOX
      increases the activity of lysosomes, which may contribute to cell injury in an
      "oncotic" manner and also demonstrate the proinflammatory potency of the drug.
      Furthermore, the decreased acidification of cytoplasm upon activation of A(3)R
      may attenuate the ongoing inflammatory response. The present study identifies a
      novel role for A(3)R selective agonist Cl-IB-MECA and suggests its importance in
      regulating cardiac cellular function.

PMID- 12056855
TI  - Identification of a novel role for sphingolipid signaling in TNF alpha and
      ischemic preconditioning mediated cardioprotection.
AB  - TNF alpha administration mimics ischemic preconditioning and neutralizing
      antibodies to TNF alpha and IL-1 beta abolish exercise-induced preconditioning.
      However, the pharmacology of TNF alpha's cardioprotective effects and associated
      downstream signaling events has not been delineated. We evaluated the temporal
      and dose specific requirements of TNF alpha to function as a preconditioning
      mimetic. Furthermore we postulated that the preconditioning effect of TNF alpha
      might be orchestrated via sphingolipid signaling. The cardioprotective effect of
      TNF alpha and the role of sphingolipid signaling were assessed using a classical
      preconditioning protocol in the isolated perfused rat heart with the measurement
      of infarct size and contractile function modulation in response to index ischemia
      and reperfusion. Recombinant TNF alpha at an optimal dose of 0.5 ng/ml mimicked
      ischemic preconditioning by reducing infarct size by 60%v non-preconditioned
      ischemia-reperfusion controls (P<0.01). The infarct sparing effect of TNF alpha
      required a wash-out period prior to the index ischemic-reperfusion. Moreover, the
      classic ischemic preconditioning antagonist such as 5-hydroxydecanoate abolished
      TNF alpha preconditioning. An inhibitor of the sphingolipid signaling pathway, N
      oleoylethanolamine (NOE, 1 microm) attenuated ischemic and TNF alpha
      preconditioning. Likewise, cell-permeable C(2)-ceramide and sphingosine 1
      phosphate (sphingolipid signaling intermediates) both reproduced the
      preconditioning cardioprotective phenotype. Finally, TNF alpha and ceramide
      conferred preconditioning-like cardioprotection against post-ischemic contractile
      dysfunction and this cardioprotective effect was attenuated by NOE. In contrast,
      NOE did not reverse ischemic preconditioning enhanced post-ischemic contractile
      function. In conclusion, TNF alpha activates preconditioning-like tolerance
      against infarction and contractile dysfunction. This cardioprotection is
      mediated, in part, via activation of novel sphingolipid signaling intermediates.

PMID- 12056856
TI  - Quantitative analysis of the expression and distribution of calcium channel alpha
      1 subunit mRNA in the atria and ventricles of the rat heart.
AB  - Two distinct calcium currents are present in mammalian cardiac myocytes.
      Utilizing quantitative RT-PCR methods, we have analysed the expression patterns
      and abundance of four calcium channel alpha 1 subunit mRNAs in different regions
      of the rat heart and compared them to the known density of calcium currents
      recorded from rat atria. Our results show that Ca(V)1.2 is the most abundant of
      the four alpha 1 subunit transcripts in the rat heart. The Ca(V)1.2 message is
      more abundant in ventricle than in atria and does not vary in expression as a
      function of developmental age. Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2 mRNAs are 10-100
      times less abundant than Ca(V)1.2. Interestingly, Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2
      are expressed in both atria and ventricle. The abundance of atrial Ca(V)3.1 mRNA
      does not change significantly during development and remains high in older
      animals. In contrast, levels of atrial Ca(V)3.2 mRNA are high in embryonic tissue
      and at 3- and 4-weeks postnatal but become undetectable at 5 weeks. Expression of
      atrial Ca(V)2.3 mRNA is highest at 4-weeks postnatal and then declines gradually.
      We have previously documented that the LVA calcium current density is highest
      within 4-5 weeks after birth and then declines gradually reaching less than 30%
      of its maximal value at 12-14 weeks. The complex relationship between atrial LVA
      current density and the abundance of Ca(V)2.3, Ca(V)3.1 and Ca(V)3.2 mRNA
      suggests that their contribution to the cardiac LVA current may vary as a
      function of postnatal age.

PMID- 12056857
TI  - Functional and molecular characterization of a T-type Ca(2+) channel during fetal
      and postnatal rat heart development.
AB  - T-type calcium current (I(CaT)) is distributed among a large variety of species
      and tissues. The main functions of I(CaT) are thought to be related to pacemaker
      activity and to the cell cycle. Using the whole-cell patch-clamp configuration,
      we showed that fetal rat ventricular cells exhibit an I(CaT) with
      electrophysiological and pharmacological characteristics similar to those already
      described for this current. We investigated I(CaT) density and found that this
      current was mainly expressed in fetal cells and remained stable until birth
      (3.1+/-0.3 pA/pF for 18-day-old fetus, n=9). I(CaT) density decreased soon after
      birth (2.0+/-0.3 pA/pF, n=6, 1.1+/-0.2 pA/pF, n=5, for 1- and 5-day-old rats,
      respectively) and was no longer detected in 21-day-old rats. The rat ventricular
      cells express an alpha 1H isoform in addition to a homologous alpha 1G variant.
      Interestingly, the Ni(2+) sensitivity of I(CaT) indicates that in newborn
      myocytes, I(CaT) is only generated by alpha 1G subunits, whereas both alpha 1G
      and alpha 1H subunits participate in the fetal I(CaT). Moreover, the relative
      contribution of each subunit varies during fetal developmental stages, with a
      major contribution of alpha 1H in 16-day-old fetuses. Through quantitative RT-PCR
      we showed that the amount of both alpha 1G and alpha 1H transcripts are
      developmentally regulated. In fetuses of less than 18 days and in newborn rats
      after 1 day old, the transcriptional levels of alpha 1G and alpha 1H subunits
      clearly mismatch the functional contribution of these subunits to I(CaT).
      However, in perinatal period, the amount of alpha 1G mRNA seems to be in
      accordance to alpha 1G-related I(CaT) density. In conclusion, we showed that
      I(CaT) is mainly expressed during fetal stages, that alpha 1G and alpha 1H
      differentially participate to I(CaT) and that alpha 1G and alpha 1H isoforms are
      regulated by both transcriptional and post-transcriptional mechanisms.

PMID- 12056858
TI  - Length dependence of cardiac myofilament Ca(2+) sensitivity in the presence of
      substitute nucleoside triphosphates.
AB  - Although ATP is the immediate source of energy for muscle contraction other
      nucleoside triphosphates (NTP) can substitute for ATP as substrates for myosin
      and as sources of energy for contraction of skinned muscle fibers. However,
      experiments with skinned skeletal muscle fibers in the presence of substitute NTP
      indicate significant differences with respect to cross-bridge kinetics, force
      generation, and Ca(2+) regulation. In this study the length dependence of Ca(2+)
      sensitivity of skinned bovine cardiac muscle was analyzed in the presence of
      MgATP, MgCTP, MgUTP, and MgITP. Ca(2+) regulation in the presence of MgCTP and
      MgUTP was essentially the same as in the presence of MgATP, although the maximum
      force generated (at sarcomere length 2.4 microm) was about 25% less. However, the
      length dependence of Ca(2+) sensitivity was eliminated in the presence of MgUTP.
      With MgITP the maximum force generated (at sarcomere length 2.4 microm) was about
      the same as in the presence of MgATP, but there was an impairment of relaxation
      such that at pCa 8 the force developed was about 50-60% of that developed at pCa
      5. Moreover, the Ca(2+)-dependent component showed no length-dependent
      sensitivity. Thus length modulation of Ca(2+) sensitivity is a function of the
      myosin substrate. Taken in conjunction with other data, the results are
      consistent with the hypothesis that length-dependence of Ca(2+) sensitivity is
      modulated at a step upstream from the force-generating reaction.

PMID- 12056859
TI  - Dinitrophenol pretreatment of rat ventricular myocytes protects against damage by
      metabolic inhibition and reperfusion.
AB  - We have investigated the protective effects of pretreatment with the
      mitochondrial uncoupler 2,4-dinitrophenol on the cellular damage induced by
      metabolic inhibition (with cyanide and iodoacetic acid) and reperfusion in
      freshly isolated adult rat ventricular myocytes. Damage was assessed from changes
      in cell length and morphology measured using video microscopy. Intracellular
      Ca(2+), mitochondrial membrane potential, and NADH were measured using fura-2,
      tetramethylrhodamine ethyl ester and autofluorescence, respectively. During
      metabolic inhibition myocytes developed rigor, and on reperfusion 73.6+/-8.1%
      hypercontracted and 10.8+/-6.7% recovered contractile function in response to
      electrical stimulation. Intracellular Ca(2+) increased substantially, indicated
      by a rise in the fura-2 ratio (340/380 nm) on reperfusion from 0.86+/-0.04 to
      1.93+/-0.18. Myocytes pretreated with substrate-free Tyrode containing 50 microm
      dinitrophenol showed reduced reperfusion injury: 29.0+/-7.4% of cells
      hypercontracted and 65.3+/-7.3% recovered contractile function (P<0.001 vs
      control). The fura-2 ratio on reperfusion was also lower at 1.01+/-0.08.
      Fluorescence measurements showed that dinitrophenol caused mitochondrial
      depolarisation, and decreased NADH. The presence of the substrates glucose and
      pyruvate reduced these effects, and abolished the protection against damage by
      metabolic inhibition and reperfusion. However protection was unaffected by block
      of ATP-sensitive potassium channels. Thus the protective effects of pretreatment
      with dinitrophenol may result from a reduction in NADH in response to
      mitochondrial depolarisation.

PMID- 12056860
TI  - Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic
      dilated cardiomyopathy.
AB  - Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the
      autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have
      undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST
      ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty
      five patients with IDCM, 17 patients with ischemic left ventricle dysfunction
      (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb
      ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In
      immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2
      isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last
      146 amino acids did not react with AAb-ANT, indicating that the main epitopes are
      in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this
      region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT
      is the primary target of AAb-ANT. The most significant epitopes belong to the M2
      and M3 hydrophilic loops of ANT suggesting that apart from being essential for
      its activity, these loops are highly immunogenic.

PMID- 12056861
TI  - Lethal effect of cytokine-induced nitric oxide and peroxynitrite on cultured rat
      cardiac myocytes.
AB  - We examined the cytotoxic effect of iNOS-generated NO in cultured cardiac
      myocytes treated with IL-1 beta, IFN- gamma and LPS. Treatment of the myocytes
      with cytokines for 48 h resulted in a marked NO production, a significant decline
      in cellular ATP content, and a significant increase in myocyte death with
      morphological characteristics of necrosis. Moreover, immunohistochemical
      examination showed that the cytokines caused nitrotyrosine formation in the
      injured myocytes. Uric acid and L-cysteine which have the ability to quench
      peroxynitrite significantly attenuated these cytokine-induced effects, although
      they did not alter NO production or the decline in cellular ATP. These data
      suggest that NO production induced by cytokines can not only cause deleterious
      effects in the myocardial energy balance but also induce myocytes necrosis,
      through the formation of peroxynitrite.

PMID- 12056862
TI  - On reducing the statespace of hidden Markov models for the identity by descent
      process.
AB  - Important methods for calculating likelihoods of genealogical relationships and
      mapping genes are based on hidden Markov models for the process of identity by
      descent along chromosomes. The computational time for the algorithms depends
      critically on the size of the statespace of the hidden Markov model. We describe
      the maximal grouping together of states of the model to reduce the size of the
      statespace. This grouping is based on pedigree symmetries. We also present an
      efficient algorithm for finding the maximal grouping.

PMID- 12056863
TI  - Mutation-selection balance: ancestry, load, and maximum principle.
AB  - We analyze the equilibrium behavior of deterministic haploid mutation-selection
      models. To this end, both the forward and the time-reversed evolution processes
      are considered. The stationary state of the latter is called the ancestral
      distribution, which turns out as a key for the study of mutation-selection
      balance. We find that the ancestral genotype frequencies determine the
      sensitivity of the equilibrium mean fitness to changes in the corresponding
      fitness values and discuss implications for the evolution of mutational
      robustness. We further show that the difference between the ancestral and the
      population mean fitness, termed mutational loss, provides a measure for the
      sensitivity of the equilibrium mean fitness to changes in the mutation rate. The
      interrelation of the loss and the mutation load is discussed. For a class of
      models in which the number of mutations in an individual is taken as the trait
      value, and fitness is a function of the trait, we use the ancestor formulation to
      derive a simple maximum principle, from which the mean and variance of fitness
      and the trait may be derived; the results are exact for a number of limiting
      cases, and otherwise yield approximations which are accurate for a wide range of
      parameters. These results are applied to threshold phenomena caused by the
      interplay of selection and mutation (known as error thresholds). They lead to a
      clarification of concepts, as well as criteria for the existence of error
      thresholds.

PMID- 12056864
TI  - Potential impacts of multiple partners on mycorrhizal community dynamics.
AB  - The significance of arbuscular mycorrhizal (AM) fungi in terrestrial ecosystems
      is widely acknowledged, but the causes and consequences of diversity in these
      fungi are not well understood. A recent frequency-dependent model suggests that
      dynamics within mycorrhizal mutualisms could promote the coexistence of at least
      two competing plant species and two competing fungal species within a community.
      Models are developed here in which simultaneous association with multiple
      partners may result in elevated or depressed fitness relative to association with
      either partner alone. This increases the range of conditions under which negative
      feedback occurs and coexistence of all four species is possible. Differences
      between plants in the relative proportions of fungi at which maximum fitness
      occurs may facilitate coexistence, as may differences between fungi in their
      abilities to establish interplant connections. These models suggest additional
      mechanisms by which mutualistic interactions could promote local diversity of
      plants and AM fungi.

PMID- 12056865
TI  - Population-level consequences of antipredator behavior: a metaphysiological model
      based on the functional ecology of the leaf-eared mouse.
AB  - We present a predator-prey metaphysiological model, based on the available
      behavioral and physiological information of the sigmodontine rodent Phyllotis
      darwini. The model is focused on the population-level consequences of the
      antipredator behavior, performed by the rodent population, which is assumed to be
      an inducible response of predation avoidance. The decrease in vulnerability is
      explicitly considered to have two associated costs: a decreasing foraging success
      and an increasing metabolic loss. The model analysis was carried out on a reduced
      form of the system by means of numerical and analytical tools. We evaluated the
      stability properties of equilibrium points in the phase plane, and carried out
      bifurcation analyses of rodent equilibrium density under varying conditions of
      three relevant parameters. The bifurcation parameters chosen represent predator
      avoidance effectiveness (A), foraging cost of antipredator behavior (C(1)'), and
      activity-metabolism cost (C(4)'). Our analysis suggests that the trade-offs
      involved in antipredator behavior plays a fundamental role in the stability
      properties of the system. Under conditions of high foraging cost, stability
      decreases as antipredator effectiveness increases. Under the complementary
      scenario (not considering the highest foraging costs), the equilibria are either
      stable when both costs are low, or unstable when both costs are higher,
      independent of antipredator effectiveness. No evidence of stabilizing effects of
      antipredator behavior was found.

PMID- 12056866
TI  - The effect of migration during the divergence.
AB  - The mean and variance of the number of nucleotide differences were obtained when
      the ancestral population diverged with migration. The number of nucleotide
      differences obtained indicates that not only the migration rate but also the
      period of migration has influence on a population structure. According to the
      migration rate and the period of migration, populations behave approximately as a
      single unit, diverged and isolated populations, two populations under
      equilibrium, or none of them. When sigma m(t) is about one, the variance of the
      number of nucleotide differences becomes large, where sigma m(t) is the sum of
      the migration rate for the period of migration. The distribution of the estimated
      divergence time was also obtained using computer simulations. It was found that
      the divergence time can be explained by sigma m(t). That is, the divergence time
      is mostly estimated as the time when sigma m(t) is less than 1.

PMID- 12056867
TI  - Physio-mitotic theory and a new concept of cancer development.
AB  - In the physio-mitotic theory, general mitosis consists of two different types:
      maturation and duplication. While being co-regulated by mechanisms involving
      maturation and duplication factors, these two types of mitotic activities each
      play a respective role in the antagonistic histological development of the other.
      According to the theory of systematic organization, each type of organic tissue
      is always developed and established under certain physiological conditions. As an
      organoid tissue, cancerous tissue must also fundamentally develop according to
      that theory. Consequently, a new concept of cancer development should be devised
      based on the physio-mitotic theory.

PMID- 12056868
TI  - Physio-mitotic theory and a new concept of embryological differentiation.
AB  - According to the physio-mitotic theory described previously by the authors
      (10,11), general mitosis consists of two different types: essential duplication
      and converted maturation. In general embryological differentiation, progression
      for the most fundamental blastocysts of the three germ layers to the immature
      stem cells comprising functional organic tissues is dependent on the essential
      duplication mitosis. This mitosis replicates stem cells while gradually
      initiating latent cellularities whereas the converted maturation process merely
      amplifies these latent cellularlities by maturing the basic cells in
      differentiated functional end cells with a pre-determined life span. The
      differentiation from the three-germ layer to embryologically organized tissues is
      dependent on duplication mitosis while being regulated by interactions with
      maturation mitosis. Thus, the complicated embryonic differentiation must be
      established in each type of organic tissue. During the process, these two types
      of mitosiseach play an antagonistic role in the embryological development of the
      other. This is another application of the physio-mitotic theory.

PMID- 12056869
TI  - Leukemia eradication and the effect of maturation factor.
AB  - As described previously (1), the development of leukemia might be attributable to
      the deteriorated effect of a maturation factor on the relevant type of the
      leukemic leukocytes, rather than a certain cellular defect initiated in the
      individual leukemic leukocytes. Thus, the eradication of the leukemia should
      depend on re-establishing the effect of the maturation factor, rather than
      persistent destruction of individual leukemia leukocytes. The most powerful
      effect of the maturation factor may be exerted throughout the mitotic duplication
      process of the most immature fibro-blastocysts in an in vitro cell culture. Thus,
      to achieve leukemia eradication, this specific cell culture, which might
      indefinitely be duplicating the immature fibro-blastocysts in the lineage of
      leukemic leukocytes, should be investigated and developed. Additionally, a
      technical method of extracting the maturation factor for the maturation mitosis
      of leukemic leukocytes should be devised and developed in the future.

PMID- 12056870
TI  - Embryonic and fetal cells which are not diseased or defective; possible sources
      of genes for disease prevention or treatment.
AB  - Cancer and other diseases may be a natural biological event, the activities of
      which may be dependent on the constitution of the individual. Where fetal and
      embryonic cells are not diseased or faulty or defective, they may be useful as
      therapies against cancer and other diseases.

PMID- 12056871
TI  - Immune response, nitric oxide, autonomic dysfunction and stroke: a puzzling
      linkage on Trypanosoma cruzi infection.
AB  - Trypanosoma cruzi (T. cruzi) is a tissue parasite causing American
      trypanosomiasis or Chagas' disease (ChD) affecting, mostly, the cardiovascular
      and gastrointestinal systems. We have recently found that people infected by T.
      cruzi are also more prone to developing ischemic strokes than the general
      population, even without heart complications; the pathomechanism of it is not yet
      well understood. However, after infection occurs, immune response induces
      endothelial dysfunction due to an endothelial nitric oxide synthase (eNOS)
      inhibition and increased activity of inducible nitric oxide synthase (iNOS).
      These factors are active in inducing vasoconstriction and cerebral microvascular
      spasms, leading to ischemic stroke. In addition, patients with ChD, regardless of
      cardiopathy, also have autonomic dysfunction, all of which may enhance the risk
      of developing ischemic stroke. Moreover, the possibility that these
      neuroimmunomodulatory pathways are disturbed in patients with other types of
      stroke seems possible, and is worthy of investigation.

PMID- 12056872
TI  - Are hyperostosis frontalis interna and leptin linked? a hypothetical approach
      about hormonal influence on human microevolution.
AB  - It is striking that evidence for hyperostosis frontalis interna - a phenomenon of
      exclusive bilateral thickening of frontal endocranial surface - in archaeological
      samples is very rare in contrast to its modern prevalence. Because
      microevolutionary changes have been shown for various human characteristics any
      alteration of hormonal levels is very likely. Selection pressure was definitively
      higher in earlier times. This favoured prolonged alertness in order to access
      sufficient food, shorter feeling of satiety, lower level of fat metabolism, lower
      metabolic rates and, therefore, lower level of leptin - a 167 amino acid peptide
      mainly involved in human total body fat regulation. Its effects on bone
      metabolism are still debated. Nevertheless, we postulate the following
      hypothesis: In humans a decrease of selective pressure favoured an increased
      metabolic rate. This, being related to the higher level of leptin caused an
      increase of localized bony overgrowth like hyperostosis frontalis interna.

PMID- 12056873
TI  - Probiotics as an adjuvant to detoxification protocols.
AB  - Autism is a developmental disease characterized by a spectrum of symptoms ranging
      from decreased verbal skills and social withdrawal, to repetitive behavior and
      violent outbursts. Genetic analysis has yielded a few potentially interesting
      genes, however no clear linkage has been established. For this reason, it has
      been suggested that the etiology of autism may involve multiple loci. This, in
      large part, explains why so many different theories abound. One such theory is
      that of mercury poisoning. Environmentally acquired mercury, either through some
      causal contact or through vaccination, has been postulated as the culprit.
      Mercury is thought to be exerting its neurological effect on the brain. The
      standard treatment has been to apply chelating agents in an attempt to extricate
      the mercury. One missing component in the treatment is the utilization of the
      body's own detoxification mechanisms. Arguably the largest detoxification
      component of the body, the endogenous enteric bacteria are an enormous reservoir,
      which can be constantly and safely replenished. This paper discusses the use of
      high-dose probiotics as an adjuvant for detoxification protocols with an emphasis
      on use in autistics.

PMID- 12056874
TI  - The Achilles' heel of HIV.
AB  - A virus uses surface molecules to enter the cell and subsequently multiplies
      using the cell's machinery. Vaccination induces the whole immunological
      capability to get rid of the virus. However, viruses found several ways to escape
      from immunological elimination. Blocking viral entry is another way to prevent
      viral spread. Here, we describe a method to block HIV entry by inhibiting the
      association of the two viral proteins that are involved in viral entry.

PMID- 12056875
TI  - Are acetylcholine-induced acetyl groups driving fuel cells in the systems of
      transducin, t and G proteins?
AB  - Life is completely dependent on a support of energy which is generated by the
      direct absorption of light or by the reduction of oxygen. Metabolized food yields
      ac(et)yl groups which are utilized in the reduction of oxygen with the assistance
      of many other compounds. Acetylcholine appears to be an important substance for
      the transportation of acetyl groups. Acetylcholine activates systems regulated by
      transducin, t and G proteins, probably Se enzymes, reacting by similar mechanisms
      in triggered reactions ending in nerve or muscle signals. These activations are
      performed by GTP (or ATP), probably resulting from the reactions of acetylcholine
      induced acetyl groups. The inactivation-activation states of these systems are
      regulated by changes of GTP to cGMP to GMP which form a loop.Diminished support
      of energy to systems, because of impaired charge transfer to oxygen, may be
      responsible for many diseases. For example, there is a low level of acetylcholine
      in the brains of patients with Alzheimer's disease.

PMID- 12056876
TI  - The role of neurofibromin and melatonin in pathogenesis of pseudarthrosis after
      spinal fusion for neurofibromatous scoliosis.
AB  - We might hypothesize that the high rate of pseudarthrosis after spinal fusion for
      neurofibromatous scoliosis is related to two factors: the absence of
      neurofibromin and melatonin deficiency. Loss of the up-regulation of
      neurofibromin during the healing process might abolish the bone-forming effects
      mediated through platelet-derived growth factor (PDGF) and transforming growth
      factor (TGF) beta1. The absence of neurofibromin might cause an increase in the
      Ras activity that increases the mitogen-activated protein kinase (MAPK) with
      resultant disturbance of the regulatory mechanism of core binding transcription
      factor (Cbfa 1) and increase of osteocalcin. These effects might inhibit bone
      formation. Melatonin deficiency might cause defective bone formation and favour
      excess fibrous tissue formation.

PMID- 12056877
TI  - Possible role of HMG-CoA reductase inhibitors for the treatment of sudden
      sensorineural hearing loss (SSHL).
AB  - The term 'idiopathic' is used to design sudden sensorineural hearing loss when
      causative factors cannot be identified. In most cases a viral infection or a
      circulatory defect are considered to play a significant role when an alternative
      satisfactory explanation cannot be found. However some significant points remain
      unclear, since the great variability in age and general conditions of the
      affected people makes it difficult to find a reliable interpretation of the exact
      nature of this phenomenon which is reasonably considered to have a multifactorial
      origin. Under these conditions many different therapeutic strategies have been
      put forward, thus suggesting some degree of uncertainty not only about the
      pathogenetic mechanisms of the disease but also on the actual effectiveness of
      the disparate treatment approaches. In this paper the use of statins in sudden
      sensorineural hearing loss is firstly proposed on the basis of their metabolic
      and hemodynamic effects, and the possible clinical implications are outlined.

PMID- 12056878
TI  - Implications of the network structure of cellular control circuits for the design
      of anti-cancer vaccine therapies.
AB  - I describe the use of a statistical mechanical model of a heirarchical network of
      failure-prone elements as a model for the failure of a network of interconnected
      biological elements that are or could be involved in the causation of cancer.
      From its topology, such a model predicts some of the properties of observed
      oncogene/tumour suppressor gene networks. I show that the same model suggests
      that a cancer vaccine strategy that targets 'key' network elements, such as p53
      or RAS gene products, is not the only effective strategy for a broadly effective
      anti-cancer therapy. A mixed antigen or whole cell strategy could be as effective
      as single antigen vaccines, even if the latter are targeted at the most commonly
      mutated gene products.

PMID- 12056879
TI  - Alcohol consumption in the absence of adequate nutrition may lead to activation
      of the glyoxylate cycle in man.
AB  - The consumption of alcohol prior to food intake results in alcohol metabolism
      occurring in the liver, and the liver is often damaged in chronic alcoholics.
      This paper highlights the possibility that alcohol consumption in the absence of
      adequate nutrition after an extended period of time may lead to activation of the
      glyoxylate cycle, an energy pathway associated with the conversion of fat into
      carbohydrate which until recently was thought to only exist in plants and
      bacteria.

PMID- 12056880
TI  - Proposition of treatment to improve the immune response: possible application to
      AIDS.
AB  - The molecular similarity between certain human antigenic determinants with those
      of HIV has been already described. In this matter, we have previously
      demonstrated, by a chromatographic method, the cross reactivity of human serum
      albumin with HIV gp 120. The hypothesis that this similarity could be one of the
      reasons why the virus escapes to the immune system is presented in this paper and
      a treatment is proposed to enhance the efficiency of the immune response: it is
      based on the blocking of the determinants of the self, expressed in the thymus,
      which are in common with the virus. Repeated injections within the thymus of
      neutralizing antibodies against the pathogen, obtained from a sufficiently
      distant animal species and purified by affinity chromatography, would prevent the
      T cells of the host recognizing these epitopes, common to the host and to the
      virus, from clonal deletion and would improve the immune response.

PMID- 12056881
TI  - Enzyme-based therapy for autism spectrum disorders -- is it worth another look?
AB  - Autism is a developmental disease usually manifesting within the first three
      years of life. To date, no causative agent has been found. Similarly, treatment
      options have been limited. Of the treatment options available, a number of them
      have been nutritionally based in an attempt to address one or more of the
      theories regarding the etiology of the disease. An example would be enzyme
      therapy for the digestion of purported offending neuroactive peptides
      collectively known as exorphins. This paper discusses the exorphin theory of
      autism and subsequent treatment with dietary enzyme therapy. Novel data are
      presented in support of the theory that enzymes play a critical role in autism.
      Forty-six patients between the ages of 5 and 31 were selected for inclusion in
      the study based on a diagnosis placing them in the category of the autism
      spectrum disorders (ASD). The diets were supplemented with a novel dietary enzyme
      formulation, ENZYMAID, for a period of 12 weeks. Progress was tracked according
      to the Symptom Outcome Survey (SOS) (1) form method of symptom charting and
      presented in a table for further analysis. The novel enzyme formula, ENZYMAID,
      beneficially and safely affected all 13 of the parameters measured. Improvements
      ranged from 50-90%, depending on the parameter measured. Enzyme therapy to treat
      ASD may indeed a viable option in treatment protocols. These results indicate
      that further controlled studies are warranted.

PMID- 12056882
TI  - An attempt to predict a possible existence of antiviral and antimicrobial
      activity.
AB  - It is known that many pathogenic and toxic agents may attach to binding site of
      the same endogenic receptor. Such an effect is due to the resemblance between
      chemical structures in foreign agents. One may imagine the structure which
      contains binding-site fragments and may compete with the receptor for foreign
      agents. Then next suggestions are probable: (1)The same substance may interact
      with some agents with established resemblance; (2) If substance (1) interacts
      with agents A and B and substance (2) influences agent (2) only then (2) ought to
      act at agent B as well. In terms 'key-keyhole' this means an existence of the key
      fitting several keyholes. Application of this conception has given a possibility
      to predict an anti-HIV and antimicrobial activity of an antirabies
      immunoglobulin.

PMID- 12056883
TI  - Clavanin permeabilizes target membranes via two distinctly different pH-dependent
      mechanisms.
AB  - The pH dependence of the antimicrobial and membrane activity of clavanin A, a
      peptide antibiotic that is rich in histidines and glycines, was analyzed in
      growth and membrane leakage experiments. Clavanin A more effectively inhibited
      the growth of the test organism Lactobacillus sake when the pH of the medium was
      lowered. Whereas the wild-type peptide efficiently released fluorophores from
      unilamellar vesicles at neutral pH according to a nonspecific permeabilization
      mechanism, it did not permeabilize model bilayers at low pH. It was therefore
      suggested that this peptide uses a distinct mode of action under acidic
      conditions different than that used around neutral pH. However, at low pH, the
      membrane is still the target for clavanin A, as the peptide collapsed both vital
      transmembrane proton gradients and ion gradients under these conditions. Clavanin
      A did not act as a ionophore across phospholipid bilayers, indicating that
      membrane constituents other than membrane phospholipids are involved in the
      dissipation of transmembrane ion gradients. Membrane proteins that generate
      transmembrane ion gradients are suggested to be the targets for clavanin A at low
      pH. In addition to the histidines, the three glycine residues of clavanin A are
      shown to play an important role in the specific mode of interaction with these
      membrane targets. These residues may induce a flexible hydrophobic conformation
      that allows the peptide to exert different membrane activities. This study
      demonstrates that clavanin A is a special membrane-active peptide that has access
      to two markedly distinct pH-dependent modes of actions.

PMID- 12056884
TI  - Thermodynamic, kinetic, and structural basis for recognition and repair of 8
      oxoguanine in DNA by Fpg protein from Escherichia coli.
AB  - X-ray analysis does not provide quantitative estimates of the relative importance
      of the molecular contacts it reveals or of the relative contributions of specific
      and nonspecific interactions to the total affinity of specific DNA to enzymes.
      Stepwise increase of DNA ligand complexity has been used to estimate the relative
      contributions of virtually every nucleotide unit of 8-oxoguanine-containing DNA
      to its total affinity for Escherichia coli 8-oxoguanine DNA glycosylase (Fpg
      protein). Fpg protein can interact with up to 13 nucleotide units or base pairs
      of single- and double-stranded ribo- and deoxyribo-oligonucleotides of different
      lengths and sequences through weak additive contacts with their internucleotide
      phosphate groups. Bindings of both single-stranded and double-stranded
      oligonucleotides follow similar algorithms, with additive contributions to the
      free energy of binding of the structural components (phosphate, sugar, and base).
      Thermodynamic models are provided for both specific and nonspecific DNA sequences
      with Fpg protein. Fpg protein interacts nonspecifically with virtually all of the
      base-pair units within its DNA-binding cleft: this provides approximately 7
      orders of magnitude of affinity (Delta G degrees approximately equal to -9.8
      kcal/mol) for DNA. In contrast, the relative contribution of the 8-oxoguanine
      unit of the substrate (Delta G degrees approximately equal to -0.90 kcal/mol)
      together with other specific interactions is <2 orders of magnitude (Delta G
      degrees approximately equal to -2.8 kcal/mol). Michaelis complex formation of Fpg
      protein with DNA containing 8-oxoguanine cannot of itself provide the major part
      of the enzyme specificity, which lies in the k(cat) term; the rate is increased
      by 6-8 orders of magnitude on going from nonspecific to specific
      oligodeoxynucleotides.

PMID- 12056885
TI  - Relative orientation between the beta-ionone ring and the polyene chain for the
      chromophore of rhodopsin in native membranes.
AB  - Rotational resonance solid state nuclear magnetic resonance has been used to
      determine the relative orientation of the beta-ionone ring and the polyene chain
      of the chromophore 11-Z-retinylidene of rhodopsin in rod outer segment membranes
      from bovine retina. The bleached protein was regenerated with either 11-Z-[8,18
      (13)C(2)]retinal or 11-Z-[8,16/17(13)C(2)]retinal, the latter having only one
      (13)C label at either of the chemically equivalent positions 16 and 17.
      Observation of (13)C selectively enriched in the ring methyl groups, C16/17,
      revealed alternative conformational states for the ring. Minor spectral
      components comprised around 26% of the chromophore. The major conformation
      (approximately 74%) has the chemical shift resolution required for measuring
      internuclear distances to (13)C in the retinal chain (C8) separately from each of
      these methyl groups. The resulting distance constraints, C8 to C16 and C17 (4.05
      +/- 0.25 A) and from C8 to C18 (2.95 +/- 0.15 A), show that the major portion of
      retinylidene in rhodopsin has a twisted 6-s-cis conformation. The more precise
      distance measurement made here between C8 and C18 (2.95 A) predicts that the
      chain is twisted out-of-plane with respect to the ring by a modest amount (C5-C6
      C7-C8 torsion angle = -28 +/- 7 degrees ).

PMID- 12056886
TI  - Thermal unfolding used as a probe to characterize the intra- and intersubunit
      stabilizing interactions in phosphorylating D-glyceraldehyde-3-phosphate
      dehydrogenase from Bacillus stearothermophilus.
AB  - Tetrameric phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from
      Bacillus stearothermophilus can be described as a dimer of dimers with three
      nonequivalent interfaces. To investigate the contribution of intra- and
      intersubunit interactions to GAPDH thermostability, 10 residues located either at
      the cofactor domain (amino acids 1-148 and 313-333) or at the catalytic domain
      (amino acids 149-312) were mutated and the thermal unfolding of the mutants was
      studied by differential scanning calorimetry in the absence and presence of
      saturating concentrations of NAD. Disruptions of intrasubunit interactions lead
      to a drastic decrease in thermostability of the N313T, Y283V, and W310F mutants.
      Moreover, for the N313T mutant, a weakening of cooperative interactions between
      the catalytic and the cofactor domains and an inefficient binding of NAD are
      observed. This is likely the consequences of modification or loss of the hydrogen
      bonding network associating N313 and residues 236-238 and N313 and the
      nicotinamide carboxyamide of NAD, respectively. For the residues Y283 and W310,
      which are involved in stacking hydrophobic interactions, mutating both positions
      does not affect the efficiency of NAD binding. This shows that the factors
      involved in the thermostability of the tetrameric apo GAPDH are then different
      from those induced by NAD binding. Disruption of intersubunit hydrogen bonds
      between the catalytic domain and the NAD-binding domain of a neighboring subunit
      also leads to a significant destabilization of the apo tetrameric form as
      observed for the D282G mutant. Moreover, no efficient binding of NAD is observed.
      Both results are likely the consequence of a loss of hydrogen bonds across the P
      axis and the Q-axis between D282 and R197 and between D282 and R52, respectively.
      Similar results, i.e., a destabilizing effect and inefficient NAD binding, are
      observed with the T34Q/T39S/L43Q mutant in which steric hindrance is introduced
      at the S-loop of the R-axis-related subunit via mutations at the adenosine
      subsite. The dimeric form of the D282G mutant exhibits a single partial heat
      absorption peak, whereas the Y46G/R52G mutant which exists only as a dimer shows
      two peaks. Taking into account the recent small-angle X-ray scattering studies
      which suggested that the dimeric form of the D282G mutant and of the dimeric
      Y46G/R52G mutant are of the O-R and O-P types, respectively (Vachette,
      unpublished results), we propose that the presence of one or two peaks in thermal
      unfolding of dimers is a signature of the dimer type.

PMID- 12056888
TI  - L-phenylalanine binding and domain organization in human phenylalanine
      hydroxylase: a differential scanning calorimetry study.
AB  - Human phenylalanine hydroxylase (hPAH) is a tetrameric enzyme that catalyzes the
      hydroxylation of L-phenylalanine (L-Phe) to L-tyrosine; a dysfunction of this
      enzyme causes phenylketonuria. Each subunit in hPAH contains an N-terminal
      regulatory domain (Ser2-Ser110), a catalytic domain (Asp112-Arg410), and an
      oligomerization domain (Ser411-Lys452) including dimerization and tetramerization
      motifs. Two partially overlapping transitions are seen in differential scanning
      calorimetry (DSC) thermograms for wild-type hPAH in 0.1 M Na-Hepes buffer, 0.1 M
      NaCl, pH 7.0. Although these transitions are irreversible, studies on their scan
      rate dependence support that the equilibrium thermodynamics analysis is
      permissible in this case. Comparison with the DSC thermograms for truncated forms
      of the enzyme, studies on the protein and L-Phe concentration effects on the
      transitions, and structure-energetic calculations based on a modeled structure
      support that the thermal denaturation of hPAH occurs in three stages: (i)
      unfolding of the four regulatory domains, which is responsible for the low
      temperature calorimetric transition; (ii) unfolding of two (out of the four)
      catalytic domains, which is responsible for the high-temperature transition; and
      (iii) irreversible protein denaturation, which is likely responsible for the
      observed exothermic distortion in the high-temperature side of the high
      temperature transition. Stages 1 and 2 do not appear to be two-state processes.
      We present an approach to the analysis of ligand effects on DSC transition
      temperatures, which is based on the general binding polynomial formalism and is
      not restricted to two-state transitions. Application of this approach to the L
      Phe effect on the DSC thermograms for hPAH suggests that (i) there are no binding
      sites for L-Phe in the regulatory domains; therefore, contrary to the common
      belief, the activation of PAH by L-Phe seems to be the result of its homotropic
      cooperative binding to the active sites. (ii) The regulatory domain appears to be
      involved in cooperativity through its interactions with the catalytic and
      oligomerization domains; thus, upon regulatory domain unfolding, the
      cooperativity in the binding of L-Phe to the catalytic domains seems to be lost
      and the value of the L-Phe concentration corresponding to half-saturation is
      increased. Overall, our results contribute to the understanding of the
      conformational stability and the substrate-induced cooperative activation of this
      important enzyme.

PMID- 12056887
TI  - Design, pharmacology, and NMR structure of a minimized cystine knot with agouti
      related protein activity.
AB  - The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin
      receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic
      activity. The cysteine-rich C-terminal domain of this protein, corresponding to
      AGRP(87-132), exhibits receptor binding affinity and antagonism equivalent to
      that of the full-length protein. The NMR structure of this active domain was
      recently determined and suggested that melanocortin receptor contacts were made
      primarily by two loops presented by a well-structured cystine knot domain within
      AGRP(87-132) [McNulty et al. (2001) Biochemistry 40, 15520-15527]. This
      hypothesis is tested here with NMR structure and activity studies of a 34-residue
      AGRP analogue designed to contain only the cystine knot domain. The designed
      miniprotein folds to a homogeneous product, retains the desired cystine knot
      architecture, functions as an antagonist, and maintains the melanocortin receptor
      pharmacological profile of AGRP(87-132). The AGRP-like activity of this molecule
      supports the hypothesis that indeed the cystine knot region possesses the
      melanocortin receptor contact points. Moreover, this potent AGRP analogue is
      synthetically accessible, may serve in the development of therapeutics for the
      treatment of diseases related to energy balance. and may also find use as a new
      reagent for probing melanocortin receptor structure and function.

PMID- 12056889
TI  - Electrostatic interactions in ubiquitin: stabilization of carboxylates by lysine
      amino groups.
AB  - To explore electrostatic interactions in ubiquitin, pK(a) values have been
      determined by NMR for all 12 carboxyl groups in wild-type ubiquitin and in
      variants where single lysines have been replaced by neutral residues. Aspartate
      pK(a) values in ubiquitin range from 3.1 to 3.8 and are generally less than model
      compound values. Most aspartate pK(a) values are within 0.2 pH unit of those
      predicted with a simple Tanford-Kirkwood model. Glutamate pK(a) values range from
      3.8 to 4.5, close to model compound values and differing by 0.1-0.8 pH unit from
      calculated values. To determine the role of positive charges in modulating
      carboxyl pK(a) values, we mutated lysines at positions 11, 29, and 33 to
      glutamine and threonine. NMR studies with these six single-site mutants reveal
      significant interactions of Lys 11 and Lys 29 with Glu 34 and Asp 21,
      respectively: pK(a) values for Glu 34 and Asp 21 increase by approximately 0.5
      0.8 pH unit, similar to predicted values, when the lysines are replaced by
      neutral residues. In contrast, the predicted interaction between Lys 33 and Glu
      34 is not observed experimentally. In some instances, substitution of lysine by
      glutamine and threonine did not lead to the same changes in carboxyl pK(a)
      values. These may reflect new short-range interactions between the mutated
      residues and the carboxyl groups. Carboxyl pK(a) shifts > 0.5 pH unit result from
      mutations at groups that are <5 A from the carboxyl group. No interactions are
      observed at >10 A.

PMID- 12056890
TI  - The role of surface-exposed lysines in wrapping DNA about the bacterial histone
      like protein HU.
AB  - Several basic proteins, including the ubiquitous HU proteins, serve histone-like
      functions in prokaryotes. Significant sequence conservation exists between HU
      homologues; yet binding sites varying from 9 to 37 bp have been reported. TF1, an
      HU homologue with a 37 bp binding site that is encoded by the Bacillus subtilis
      bacteriophage SPO1, binds with nM affinity to DNA that contains 5
      hydroxymethyluracil (hmU) in place of thymine and to T-containing DNA with loops.
      We evaluated the contribution of three conserved lysines to specifying the length
      of the binding site and show that Lys3 is critical for maintaining a long binding
      site in T-containing DNA: A mutant protein in which Lys3 is replaced with Gln(TF1
      K3Q) is completely deficient in forming a stable complex. The affinity for 37 bp
      hmU-containing DNA is also reduced, from approximately 3 nM for wild-type TF1 to
      approximately 90 nM for TF1-K3Q. The decrease in affinity of TF1-K3Q for hmU
      containing DNA > or = 25 bp suggests that Lys3 contacts DNA 8-9 bp distal to the
      sites of kinking. We propose that Lys3 forms an internal saltbridge to Asp26 in
      HU homologues characterized by shorter binding sites and that its surface
      exposure, and hence a longer binding site, may correlate with absence of this
      aspartate.

PMID- 12056891
TI  - Inhibition of DNA binding by NF-kappa B with pyrrole-imidazole polyamides.
AB  - Synthetic ligands that bind to predetermined DNA sequences will offer a chemical
      approach to gene regulation if inhibition of a broad range of transcription
      factors can be achieved. NF-kappa B is a transcription factor that regulates a
      multitude of genes, including those involved in immune, inflammatory, and anti
      apoptotic responses. NF-kappa B binds as heterodimer predominantly in the major
      groove. We report the design of polyamides that bind in the minor groove and
      target overlapping portions of an NF-kappa B binding site (5'-GGGACTTTCC-3'). We
      find that compounds that target the 5'-GGGACT-3' portion of the site can inhibit
      DNA binding by NF-kappa B while those that target the 5'-ACTTTCC-3' portion do
      not. Addition of NF-kappa B to the list of protein-DNA complexes that can be
      disrupted by minor groove binding ligands potentially increases the utility of
      polyamides as regulators of gene expression.

PMID- 12056892
TI  - Novel phenalenone derivatives from a marine-derived fungus exhibit distinct
      inhibition spectra against eukaryotic DNA polymerases.
AB  - A number of compounds used for cancer chemotherapy exert their effects by
      inhibiting DNA replication. New inhibitors of DNA polymerases, therefore, could
      be potential candidates for new anti-cancer drugs. This study tested the effects
      of two phenalenone-skeleton-based compounds, which were isolated from a marine
      derived fungus Penicillium sp., sculezonone-B (SCUL-B) and sculezonone-A (SCUL
      A), upon DNA polymerase activity. Both compounds inhibited bovine DNA polymerases
      alpha and gamma, moderately affected the activity of DNA polymerase epsilon, and
      had almost no effect on HIV-reverse transcriptase and an E. coli DNA polymerase I
      Klenow fragment. Most notably, whereas SCUL-A inhibited pol beta (IC(50) = 17
      microM), SCUL-B has only a weak influence upon this polymerase (IC(50) = 90
      microM). Kinetic studies showed that inhibition of both DNA polymerases alpha and
      beta by either SCUL-A or SCUL-B was competitive with respect to dTTP substrate
      and noncompetitive with the template-primer. Whereas pol alpha inhibition by SCUL
      B is competitive with respect to dATP, the inhibition by SCUL-A was found to be a
      mixed type with dATP substrate. The K(i) values of SCUL-B were calculated to be
      1.8 and 6.8 microM for DNA polymerases alpha and gamma, respectively. The K(i) of
      DNA polymerase beta for SCUL-A was 12 microM and that for DNA polymerase alpha,
      16 microM. Therefore, deletion of the OH-group at C12 enhanced inhibition of DNA
      polymerase beta. Since computational analyses of these two inhibitors revealed a
      remarkable difference in the distribution of negative electrostatic charge on the
      surface of molecules, we infer that different electrostatic charges might elicit
      different inhibition spectra from these two compounds.

PMID- 12056893
TI  - Identification of a 34 amino acid stretch within the C-terminus of histone H1 as
      the DNA-condensing domain by site-directed mutagenesis.
AB  - The C-terminus of histone H1 is necessary for the folding of polynucleosomal
      arrays into higher-order structure(s) and contains octapeptide repeats each
      having DNA binding S/TPKK motifs. These repeat motifs were earlier shown to mimic
      the DNA/chromatin-condensing properties of the C-terminus of histone H1 (Khadake,
      J. R., and Rao, M. R. S. (1995) Biochemistry 36, 1041-1051). In the present
      study, we have generated a series of C-terminal mutants of rat histone H1d and
      studied their DNA-condensation properties. The single proline to alanine mutation
      in the S/TPKK motifs either singly or in combination resulted in only a 20%
      decrease in the DNA-condensation property of histone H1. Deletion of all the
      three S/TPKK motifs resulted in a 45% decrease in DNA condensation. When the
      three octapeptide repeats encompassing the S/TPKK motifs were deleted, there was
      again a 45% decrease in DNA condensation. On the other hand, when the entire 34
      amino acid stretch (residue 145-178) was deleted, there was nearly a 90% decrease
      in DNA condensation brought about by histone H1d. Interestingly, deletion of the
      10 amino acid spacer between the octapeptide repeats (residues 161-170) also
      reduced the DNA condensation by 70%. Deletion of the region (residues 115-141)
      immediately before the 34 amino acid stretch and after the globular domain and
      the region (residues 184-218) immediately after the 34 amino acid stretch had
      only a marginal effect on DNA condensation. The importance of the 34 amino acid
      stretch, including the 10 amino acid spacer, was also demonstrated with the
      recombinant histone H1d C-terminus. We have also determined the induced alpha
      helicity of histone H1 and its various mutants in the presence of 60%
      trifluoroethanol, and the experimentally determined induced helical contents
      agree with the theoretical predictions of secondary structural elements in the C
      terminus of histone H1d. Thus, we have identified a 34 amino acid stretch in the
      C-terminus of histone H1d as the DNA-condensing domain.

PMID- 12056894
TI  - Organization of an efficient carbonic anhydrase: implications for the mechanism
      based on structure-function studies of a T199P/C206S mutant.
AB  - Substitution of Pro for Thr199 in the active site of human carbonic anhydrase II
      (HCA II)(1) reduces its catalytic efficiency about 3000-fold. X-ray
      crystallographic structures of the T199P/C206S variant have been determined in
      complex with the substrate bicarbonate and with the inhibitors thiocyanate and
      beta-mercaptoethanol. The latter molecule is normally not an inhibitor of wild
      type HCA II. All three ligands display novel binding interactions to the
      T199P/C206S mutant. The beta-mercaptoethanol molecule binds in the active site
      area with its sulfur atom tetrahedrally coordinated to the zinc ion. Thiocyanate
      binds tetrahedrally coordinated to the zinc ion in T199P/C206S, in contrast to
      its pentacoordinated binding to the zinc ion in wild-type HCA II. Bicarbonate
      binds to the mutant with two of its oxygens at the positions of the zinc water
      (Wat263) and Wat318 in wild-type HCA II. The environment of this area is more
      hydrophilic than the normal bicarbonate-binding site of HCA II situated in the
      hydrophobic part of the cavity normally occupied by the so-called deep water
      (Wat338). The observation of a new binding site for bicarbonate has implications
      for understanding the mechanism by which the main-chain amino group of Thr199
      acquired an important role for orientation of the substrate during the evolution
      of the enzyme.

PMID- 12056895
TI  - S-adenosylmethionine conformations in solution and in protein complexes:
      conformational influences of the sulfonium group.
AB  - S-Adenosylmethionine (AdoMet) and other sulfonium ions play central roles in the
      metabolism of all organisms. The conformational preferences of AdoMet and two
      other biologically important sulfonium ions, S-methylmethionine and
      dimethylsulfonioproprionic acid, have been investigated by NMR and computational
      studies. Molecular mechanics parameters for the sulfonium center have been
      developed for the AMBER force field to permit analysis of NMR results and to
      enable comparison of the relative energies of the different conformations of
      AdoMet that have been found in crystal structures of complexes with proteins. S
      Methylmethionine and S-dimethylsulfonioproprionate adopt a variety of
      conformations in aqueous solution; a conformation with an electrostatic
      interaction between the sulfonium sulfur and the carboxylate group is not
      noticeably favored, in contrast to the preferred conformation found by in vacuo
      calculations. Nuclear Overhauser effect measurements and computational results
      for AdoMet indicate a predominantly anti conformation about the glycosidic bond
      with a variety of conformations about the methionyl C(alpha)-C(beta) and C(beta)
      C(gamma) bonds. An AdoMet conformation in which the positively charged sulfonium
      sulfur is near an electronegative oxygen in the ribose ring is common.
      Comparisons of NMR results for AdoMet with those for the uncharged S
      adenosylhomocysteine and 5'-methylthioadenosine, and the anionic ATP, indicate
      that the solution conformations are not dictated mainly by molecular charge. In
      20 reported structures of AdoMet.protein complexes, both anti and syn glycosidic
      torsional angles are found. The methionyl group typically adopts an extended
      conformation in complexes with enzymes that transfer the methyl group from the
      sulfonium center, but is more folded in complexes with proteins that do not
      catalyze reactions involving the sulfur and which can use the sulfonium sulfur
      solely as a binding site. The conformational energies of AdoMet in these crystal
      structures are comparable to those found for AdoMet in solution. The sulfonium
      sulfur is in van der Waals contact with a protein heteroatom in the structures of
      four proteins, which reflects an energetically favorable contact. Interactions of
      the sulfonium with aromatic rings are rarely observed.

PMID- 12056896
TI  - Use of an in situ disulfide cross-linking strategy to map proximities between
      amino acid residues in transmembrane domains I and VII of the M3 muscarinic
      acetylcholine receptor.
AB  - In this study, we employed an in situ disulfide cross-linking strategy to gain
      insight into the structure of the inactive and active state of the M(3)
      muscarinic acetylcholine receptor. Specifically, this study was designed to
      identify residues in TM I that are located in close to Cys532 (position 7.42), an
      endogenous cysteine residue present in the central portion of TM VII. Cysteine
      residues were substituted, one at a time, into 10 consecutive positions of TM I
      (Ala71-Val80) of a modified version of the M(3) muscarinic receptor that lacked
      most endogenous cysteine residues and contained a factor Xa cleavage site within
      the third intracellular loop. Following their expression in COS-7 cells, the 10
      resulting cysteine mutant receptors were oxidized in their native membrane
      environment, either in the absence or in the presence of muscarinic ligands.
      Disulfide cross-link formation was monitored by examining changes in the
      electrophoretic mobility of oxidized and factor Xa-digested receptors on SDS
      gels. When molecular iodine was used as the oxidizing agent, the L77C receptor
      (position 1.42) was the only mutant receptor that displayed significant disulfide
      cross-linking, either in the absence or in the presence of muscarinic agonists or
      antagonists. On the other hand, when the Cu(II)-(1,10-phenanthroline)(3) complex
      served as the redox catalyst, muscarinic ligands inhibited disulfide cross
      linking of the L77C receptor, probably because of impaired access of this
      relatively bulky oxidizing agent to the ligand binding crevice. The iodine cross
      linking data suggest that M(3) muscarinic receptor activation is not associated
      with significant changes in the relative orientations of the outer and/or central
      segments of TM I and VII. In bovine rhodopsin, the residues present at the
      positions corresponding to Cys532 and Leu77 in the rat M(3) muscarinic receptor
      are not located directly adjacent to each other, raising the possibility that the
      relative orientations of TM I and VII are not identical among different class I
      GPCRs. Alternatively, dynamic protein backbone fluctuation may occur, enabling
      Cys532 to move within cross-linking distance of Leu77 (Cys77).

PMID- 12056897
TI  - Structure of oxalate decarboxylase from Bacillus subtilis at 1.75 A resolution.
AB  - Oxalate decarboxylase is a manganese-dependent enzyme that catalyzes the
      conversion of oxalate to formate and carbon dioxide. We have determined the
      structure of oxalate decarboxylase from Bacillus subtilis at 1.75 A resolution in
      the presence of formate. The structure reveals a hexamer with 32-point symmetry
      in which each monomer belongs to the cupin family of proteins. Oxalate
      decarboxylase is further classified as a bicupin because it contains two cupin
      folds, possibly resulting from gene duplication. Each oxalate decarboxylase cupin
      domain contains one manganese binding site. Each of the oxalate decarboxylase
      domains is structurally similar to oxalate oxidase, which catalyzes the manganese
      dependent oxidative decarboxylation of oxalate to carbon dioxide and hydrogen
      peroxide. Amino acid side chains in the two metal binding sites of oxalate
      decarboxylase and the metal binding site of oxalate oxidase are very similar.
      Four manganese binding residues (three histidines and one glutamate) are
      conserved as well as a number of hydrophobic residues. The most notable
      difference is the presence of Glu333 in the metal binding site of the second
      cupin domain of oxalate decarboxylase. We postulate that this domain is
      responsible for the decarboxylase activity and that Glu333 serves as a proton
      donor in the production of formate. Mutation of Glu333 to alanine reduces the
      catalytic activity by a factor of 25. The function of the other domain in oxalate
      decarboxylase is not yet known.

PMID- 12056898
TI  - Mapping the targeted membrane pore formation mechanism by solution NMR: the nisin
      Z and lipid II interaction in SDS micelles.
AB  - Nisin is an example of type-A lantibiotics that contain cyclic lanthionine rings
      and unusual dehydrated amino acids. Among the numerous pore-forming antimicrobial
      peptides, type-A lantibiotics form an unique family of post-translationally
      modified peptides. Via the recognition of cell wall precursor lipid II, nisin has
      the capacity to form pores against Gram-positive bacteria with an extremely high
      activity in the nanomolar (nM) range. Here we report a high-resolution NMR
      spectroscopy study of nisin/lipid II interactions in SDS micelles as a model
      membrane system in order to elucidate the mechanism of molecular recognition at
      residue level. The binding to lipid II was studied through (15)N-(1)H HSQC
      titration, backbone amide proton temperature coefficient analysis, and
      heteronuclear (15)N[(1)H]-NOE relaxation dynamics experiments. Upon the addition
      of lipid II, significant changes were monitored in the N-terminal part of nisin.
      An extremely low amide proton temperature coefficient (Delta delta/Delta T) was
      found for the amide proton of Ala3 (> -0.1 ppb/K) in the complex form. This
      suggests tight hydrogen bonding and/or isolation from the bulk solvent for this
      residue. Large chemical shift perturbations were also observed in the first two
      rings. In contrast, the C-terminal part of nisin was almost unaffected. This part
      of the molecule remains flexible and solvent-exposed. On the basis of our
      results, a multistep pore-forming mechanism is proposed. The N-terminal part of
      nisin first binds to lipid II, and a subsequent structural rearrangement takes
      place. The C-terminal part of nisin is possibly responsible for the activation of
      the pore formation. In light of the emerging antibiotic resistance problems, an
      understanding of the specific recognition mechanism of nisin with lipid II at the
      residue specific level may therefore aid in the development of novel antibiotics.

PMID- 12056899
TI  - The "cap-binding slot" of an mRNA cap-binding protein: quantitative effects of
      aromatic side chain choice in the double-stacking sandwich with cap.
AB  - The N7-methylguanine portion of the mRNA cap structure interacts with cap-binding
      proteins via an unusual double-stacking arrangement in which the positively
      charged cap is sandwiched between two parallel-oriented aromatic protein side
      chains. Three-dimensional costructures of cap with two mRNA cap-binding proteins,
      namely, translational initiation factor eIF4E and VP39 (the vaccinia virus
      encoded mRNA cap-specific 2'-O-methyltransferase), have heretofore been reported.
      Despite striking similarities between the two proteins in the double stack with
      the cap, the stack differs most notably in the species of stacked side chain
      donated by the protein. Whereas eIF4E employs two tryptophans, VP39 uses a
      tyrosine and a phenylalanine. Here, we have generated tryptophan substitutions in
      VP39. Tryptophan substitution was shown, crystallographically, not to disrupt the
      maintenance of a bona fide parallel stack. However, the single-tryptophan and
      double-tryptophan substitutions were associated with increased affinity for cap
      nucleoside by factors of 10 and 50, respectively. VP39 interacted more strongly
      with a true substrate (containing portions of RNA downstream of the cap in
      addition to the cap itself) than with isolated cap nucleoside, by several orders
      of magnitude. VP39 mutants with tryptophan substitution at position 180 exhibited
      apparent defects in substrate catalytic rate during the first turnover cycle,
      indicating the possibility of an exquisite sensitivity of the catalytic center to
      subtle changes in substrate position brought about by alterations in the cap
      binding slot. The X-ray structure of VP39 with a genuine nucleobase analogue of
      N7-methylguanosine, namely, N7,9-dimethylguanine, indicated that the N7
      methylguanosine rotational orientation within the stack is a property of the cap
      nucleobase itself.

PMID- 12056900
TI  - Purification and partial characterization of a DNA 3'-phosphatase from
      Schizosaccharomyces pombe.
AB  - Cells that depend on oxygen for survival constantly produce reactive oxygen
      species that attack DNA to produce a variety of lesions, including single-strand
      breaks with 3'-blocking groups such as 3'-phosphate and 3'-phosphoglycolate.
      These 3'-blocking ends prevent the activity of DNA polymerase and are generally
      removed by DNA repair proteins with 3'-diesterase activity. We report here the
      purification and partial characterization of a 45 kDa protein from
      Schizosaccharomyces pombe total extract based on the ability of this protein to
      process bleomycin- or H(2)O(2)-damaged DNA in vitro to allow DNA repair synthesis
      by DNA polymerase I. Further analysis revealed that the 45 kDa protein removes 3'
      phosphate ends created by the Escherichia coli fpg AP lyase following the
      incision of AP site but is unable to process the 3'-alpha,beta unsaturated
      aldehyde generated by E. coli endonuclease III. The protein cannot cleave DNA
      bearing AP sites, suggesting that it is not an AP endonuclease or AP lyase. We
      conclude that the 45 kDa protein purified from S. pombe is a DNA 3'-phosphatase.

PMID- 12056901
TI  - Thermodynamics of aminoglycoside-rRNA recognition: the binding of neomycin-class
      aminoglycosides to the A site of 16S rRNA.
AB  - We use spectroscopic and calorimetric techniques to characterize the binding of
      the aminoglycoside antibiotics neomycin, paromomycin, and ribostamycin to a RNA
      oligonucleotide that models the A-site of Escherichia coli 16S rRNA. Our results
      reveal the following significant features: (i) Aminoglycoside binding enhances
      the thermal stability of the A-site RNA duplex, with the extent of this thermal
      enhancement decreasing with increasing pH and/or Na(+) concentration. (ii) The
      RNA binding enthalpies of the aminoglycosides become more exothermic (favorable)
      with increasing pH, an observation consistent with binding-linked protonation of
      one or more drug amino groups. (iii) Isothermal titration calorimetry (ITC)
      studies conducted as a function of buffer reveal that aminoglycoside binding to
      the host RNA is linked to the uptake of protons, with the number of linked
      protons being dependent on pH. Specifically, increasing the pH results in a
      corresponding increase in the number of linked protons. (iv) ITC studies
      conducted at 25 and 37 degrees C reveal that aminoglycoside-RNA complexation is
      associated with a negative heat capacity change (Delta C(p)), the magnitude of
      which becomes greater with increasing pH. (v) The observed RNA binding affinities
      of the aminoglycosides decrease with increasing pH and/or Na(+) concentration. In
      addition, the thermodynamic forces underlying these RNA binding affinities also
      change as a function of pH. Specifically, with increasing pH, the enthalpic
      contribution to the observed RNA binding affinity increases, while the
      corresponding entropic contribution to binding decreases. (vi) The affinities of
      the aminoglycosides for the host RNA follow the hierarchy neomycin > paromomycin
      > ribostamycin. The enhanced affinity of neomycin relative to either paromomycin
      or ribostamycin is primarily, if not entirely, enthalpic in origin. (vii) The
      salt dependencies of the RNA binding affinities of neomycin and paromomycin are
      consistent with at least three drug NH(3)(+) groups participating in
      electrostatic interactions with the host RNA. In the aggregate, our results
      reveal the impact of specific alterations in aminoglycoside structure on the
      thermodynamics of binding to an A-site model RNA oligonucleotide. Such systematic
      comparative studies are critical first steps toward establishing the
      thermodynamic database required for enhancing our understanding of the molecular
      forces that dictate and control aminoglycoside recognition of RNA.

PMID- 12056902
TI  - The amino terminus of opsin translocates "posttranslationally" as efficiently as
      cotranslationally.
AB  - Opsin, a member of the G-protein-coupled receptor family, is a polytopic membrane
      protein that does not encode a cleaved amino-terminal signal sequence. The amino
      terminus of opsin precedes the first known targeting information, suggesting that
      it translocates across the endoplasmic reticulum (ER) membrane after synthesis,
      uncoupled from translation. However, translocation across the mammalian ER is
      believed to be coupled to protein synthesis. In this study we show that opsin,
      within a range of nascent peptide lengths, targets and translocates equally
      efficiently co- and posttranslationally. Longer nascent opsin peptides have a
      lower efficiency of cotranslational translocation but an even lower efficiency of
      posttranslational translocation. We also show that SRP is required for both co-
      and posttranslational targeting.

PMID- 12056903
TI  - Minimum number of 2'-O-(2-aminoethyl) residues required for gene knockout
      activity by triple helix forming oligonucleotides.
AB  - Triple helix forming oligonucleotides (TFOs) that bind chromosomal targets in
      living cells may become tools for genome manipulation, including gene knockout,
      conversion, or recombination. However, triplex formation by DNA third strands,
      particularly those in the pyrimidine motif, requires nonphysiological pH and
      Mg(2+) concentration, and this limits their development as gene-targeting
      reagents. Recent advances in oligonucleotide chemistry promise to solve these
      problems. For this study TFOs containing 2'-O-methoxy (2'-OMe) and 2'-O-(2
      aminoethyl) (2'-AE) ribose substitutions in varying proportion have been
      constructed. The TFOs were linked to psoralen and designed to target and
      mutagenize a site in the hamster HPRT gene. T(m) analyses showed that triplexes
      formed by these TFOs were more stable than the underlying duplex, regardless of
      2'-OMe/2'-AE ratio. However, TFOs with 2'-AE residues were more stable in
      physiological pH than those with only 2'-OMe sugars, as a simple function of 2'
      AE content. In contrast, gene knockout assays revealed a threshold requirement-
      TFOs with three or four 2'-AE residues were at least 10-fold more active than the
      TFO with two 2'-AE residues. The HPRT knockout frequencies with the most active
      TFOs were 300-400-fold above the background, whereas there was no activity
      against the APRT gene, a monitor of nonspecific mutagenesis.

PMID- 12056904
TI  - Vinylphosphonate internucleotide linkages inhibit the activity of PcrA DNA
      helicase.
AB  - During the past 5 years a great deal of structural and biochemical information
      has given us a detailed insight into the molecular mechanism of action of the
      PcrA DNA helicase and challenged previous notions about the molecular mechanism
      of action of helicases in general. Despite this wealth of information the
      mechanisms of the interaction of helicases with their DNA substrates and their
      unidirectional translocation along ssDNA are poorly understood. In this study, we
      synthesized a chemically modified DNA substrate with reduced backbone rotational
      flexibility and minimal steric hindrance and studied its effect on the activity
      of the monomeric 3'-5' DNA helicase, PcrA. Our results show that a single
      modification on the backbone of the translocating strand is sufficient to inhibit
      the activity of PcrA helicase, suggesting that rotational flexibility of the
      backbone is important for efficient unwinding.

PMID- 12056906
TI  - Phosphorylation of p47phox sites by PKC alpha, beta II, delta, and zeta: effect
      on binding to p22phox and on NADPH oxidase activation.
AB  - Production of superoxide anions by the multicomponent enzyme of human neutrophil
      NADPH oxidase is accompanied by extensive phosphorylation of p47(phox), one of
      its cytosolic components. p47(phox) is an excellent substrate for protein kinase
      C (PKC), but the respective contribution of each PKC isoform to this process is
      not clearly defined. In this study, we found that PKC isoforms known to be
      present in human neutrophils (PKC alpha, beta, delta, and zeta) phosphorylate
      p47(phox) in a time- and concentration-dependent manner, with apparent K(m)
      values of 10.33, 3.37, 2.37, and 2.13 microM for PKC alpha, beta II, delta, and
      zeta, respectively. Phosphopeptide mapping of p47(phox) showed that, as opposed
      to PKC zeta, PKC alpha, beta II, and delta are able to phosphorylate all the
      major PKC sites. The use of p47(phox) mutants identified serines 303, 304, 315,
      320, 328, 359, 370, and 379 as targets of PKC alpha, beta II, and delta.
      Comparison of the intensity of phosphopeptides suggests that Ser 328 is the most
      phosphorylated serine. The ability of each PKC isoform to induce p47(phox) to
      associate with p22(phox) was tested by using an overlay technique; the results
      showed that all the PKC isoforms that were studied induce p47(phox) binding to
      the cytosolic fragment of p22(phox). In addition, PKC alpha, beta II, delta, and
      zeta were able to induce production of superoxide anions in a cell-free system
      using recombinant cytosolic proteins. Surprisingly, PKC zeta, which
      phosphorylates a subset of selective p47(phox) sites, induced stronger activation
      of the NADPH oxidase. Taken together, these results suggest that PKC alpha, beta
      II, delta, and zeta expressed in human neutrophils can individually phosphorylate
      p47(phox) and induce both its translocation and NADPH oxidase activation. In
      addition, phosphorylation of some serines could have an inhibitory effect on
      oxidase activation.

PMID- 12056905
TI  - DNA bending by bZIP charge variants: a unified study using electrophoretic
      phasing and fluorescence resonance energy transfer.
AB  - The role of asymmetric charge neutralization as a primary determinant of protein
      induced DNA helical bending remains controversial. Electrophoretic phasing
      experiments have been conducted previously for peptides derived from the yeast
      basic leucine zipper (bZIP) transcription factor GCN4 bound to AP-1 sites in
      duplex DNA. Mutations altering the electrostatic character of amino acids close
      to the DNA backbone result in phase-dependent gel mobility changes, interpreted
      as evidence of DNA bending. However, alternate interpretations are possible. The
      effect of electrostatic interactions on DNA conformation has now been
      investigated further, using purified peptides having indistinguishable AP-1 DNA
      affinity. Two independent techniques have been employed: electrophoretic phasing
      and fluorescence resonance energy transfer (FRET). The phasing results imply DNA
      bending by bZIP charge variants, consistent with earlier findings. FRET studies
      yield the mean 5' end to 3' end distance of AP-1 DNA when free or bound to
      neutral or charged bZIP peptides. These distances were reduced in the charged
      variant complexes relative to those in the free duplex and the wild-type complex.
      Bending of the DNA helical axis is shown by molecular modeling to be the simplest
      interpretation of these results. The electrophoretic phasing and FRET results
      thus offer two mutually supportive lines of evidence for induced bending of the
      DNA helical axis due to asymmetric changes in charge density caused by the
      electrostatic character of the amino acids residing near the DNA backbone.

PMID- 12056907
TI  - Specificity of soluble phospholipid binding sites on human factor Xa.
AB  - We explore here the specificities of lipid regulatory sites on factor X(a) that
      affect the rate of factor X(a)-catalyzed prothrombin activation. We examined a
      series of 11 phosphatidylserine (PS) analogues in order to map the structural
      features of a lipid molecule that are needed to elicit both the structural
      response and the full increase in activity that can be obtained with the PS
      molecule. Our observations are interpreted in terms of a model in which factor
      X(a) is regulated by sequential occupancy of a pair of linked lipid binding
      sites, each of which have different minimum ligand structural requirements to
      induce structural changes. The first site is apparently of higher affinity and
      recognizes diacylglycerol (DAG) as a minimal binding structure. The second site
      is occupied with an affinity slightly less than the first site only when the
      first is occupied, but binds PS with very low affinity otherwise. It recognizes
      glycerophosphorylserine (GPS) as the minimal ligand. To test this interpretation,
      experiments were performed in which more than one lipid species was present. It
      was necessary to invoke the existence of factor X(a) species containing different
      lipids at each site, each having different structural and functional responses.
      For optimal activity enhancement, both binding sites must be occupied, the first
      by PS, although the second can be occupied with other lipids.

PMID- 12056908
TI  - Plant chromosomal HMGB proteins efficiently promote the bacterial site-specific
      beta-mediated recombination in vitro and in vivo.
AB  - In the presence of an accessory DNA bending protein, the bacterial site-specific
      beta recombinase catalyzes resolution and DNA inversion. Five different maize
      high mobility group B (HMGB) proteins were examined for their potential to
      facilitate beta recombination in vitro using DNA substrates with different
      intervening distances (73-913 bp) between two directly oriented recombination
      (six) sites. All analyzed HMGB proteins (HMGB1 to HMGB5) could promote beta
      recombination, but depending on the DNA substrate with different efficiencies.
      The HMGB1 protein displayed an activity comparable to that of the natural
      promoting protein Hbsu, whereas the other HMGB proteins were less effective.
      Phosphorylation of the HMGB1 protein resulted in an increased efficiency of HMGB1
      to promote beta recombination. Analyses of DNA substrates with closely spaced six
      sites demonstrated that in the presence of HMGB1 the recombination rate was
      correlated to the distance between the six sites, but independent of the helical
      orientation of the six sites. Using a Bacillus subtilis strain defective in Hbsu,
      the coexpression of beta recombinase and HMGB1 (or a truncated HMGB1 derivative)
      revealed that a plant HMG-box domain protein is sufficient for assisting beta to
      catalyze recombination in vivo. Our results using beta recombination as a model
      system suggest that the various plant HMGB proteins (and their
      posttranslationally modified versions) have the potential of forming a repertoire
      of different DNA structures, which is compatible with the idea that the HMGB
      proteins can act as architectural factors in a variety of nucleoprotein
      structures.

PMID- 12056909
TI  - Pore formation and uncoupling initiate a Ca2+-independent degradation of
      mitochondrial phospholipids.
AB  - Mitochondria contain a type IIA secretory phospholipase A(2) that has been
      thought to hydrolyze phospholipids following Ca(2+) accumulation and induction of
      the permeability transition. These enzymes normally require millimolar Ca(2+) for
      optimal activity; however, no dependence of the mitochondrial activity on Ca(2+)
      can be demonstrated upon equilibrating the matrix space with extramitochondrial
      Ca(2+) buffers. Ca(2+)-independent activity is seen following protonophore
      mediated uncoupling, when uncoupling arises through alamethicin-mediated pore
      formation, or upon opening the permeability transition pore. Under the latter
      conditions, activity continues in the presence of excess EGTA but is somewhat
      enhanced by exogenous Ca(2+). The Ca(2+)-independent activity is best seen in
      media of high ionic strength and displays a broad pH optimum located between pH 8
      and pH 8.5. It is strongly inhibited by bromoenol lactone but not by arachidonyl
      trifluoromethyl ketone, dithiothreitol, and other inhibitors of particular
      phospholipase A(2) classes. Immunoanalysis of mitochondria and mitochondrial
      subfractions shows that a membrane-bound protein is present that is recognized by
      antibody against an authentic iPLA(2) that was first found in P388D(1) cells. It
      is concluded that mitochondria contain a distinct Ca(2+)-independent
      phospholipase A(2) that is regulated by bioenergetic parameters. It is proposed
      that this enzyme, rather than the Ca(2+)-dependent type IIA phospholipase A(2),
      initiates the removal of poorly functioning mitochondria by processes involving
      autolysis.

PMID- 12056910
TI  - Identification of a new class of inhibitors of the voltage-gated potassium
      channel, Kv1.3, with immunosuppressant properties.
AB  - The voltage-gated potassium channel, K(v)1.3, is a novel target for development
      of immunosuppressants. Using a functional (86)Rb(+) efflux assay, a new class of
      high-affinity K(v)1.3 inhibitors has been identified. The initial active in this
      series, 4-phenyl-4-[3-(2-methoxyphenyl)-3-oxo-2-azaprop-1-yl]cyclohexanone (PAC),
      which is representative of a disubstituted cyclohexyl (DSC) template, displays a
      K(i) of ca. 300 nM and a Hill coefficient near 2 in the flux assay and in voltage
      clamp recordings of K(v)1.3 channels in human T-lymphocytes. PAC displays
      excellent specificity as it only blocks members of the K(v)1 family of potassium
      channels but does not affect many other types of ion channels, receptors, or
      enzyme systems. Block of K(v)1.3 by DSC analogues occurs with a well-defined
      structure-activity relationship. Substitution at the C-1 ketone of PAC generates
      trans (down) and cis (up) isomer pairs. Whereas many DSC derivatives do not
      display selectivity in their interaction with different K(v)1.x channels, trans
      DSC derivatives distinguish between K(v)1.x channels based on their rates of C
      type inactivation. DSC analogues reversibly inhibit the Ca(2+)-dependent pathway
      of T cell activation in in vitro assays. Together, these data suggest that DSC
      derivatives represent a new class of immunosuppressant agents and that specific
      interactions of trans DSC analogues with channel conformations related to C-type
      inactivation may permit development of selective K(v)1.3 channel inhibitors
      useful for the safe treatment of autoimmune diseases.

PMID- 12056911
TI  - Mechanism of spontaneous DNA-DNA interaction of homologous linear duplexes.
AB  - Previously, we demonstrated the interaction of homologous linear duplexes with
      formation of four-way DNA structures on the model of five PCR products. We
      propose that homologous duplex interaction is initiated by the nucleation of
      several dissociated base pairs of the complementary ends of two fragments with
      Holliday junction formation, in which cross point migration occurs via spooling
      of DNA strands from one duplex to the other one, finally resulting in complete
      resolution into new or previously existing duplexes. To confirm that DNA-DNA
      interaction involves formation of four-way DNA structures with strand exchange at
      the cross point, we have demonstrated the strand exchange process between
      identical duplexes using homologous fragments, harboring either biotin label or
      (32)P-label. Incubation of the mixture resulted in the addition of (32)P-label to
      biotin-labeled fragments, and the intensity of (32)P-labeling of biotinylated
      fragments was dependent upon the incubation duration. DNA-DNA interaction is not
      based on surface-dependent denaturing, as Triton X-100 does not decrease the
      formation of complexes between DNA duplexes. The equilibrium concentration of
      Holliday junctions depends on the sequences of the fragment ends and the
      incubation temperature. The free energy of Holliday junction formation by the
      fragments with GC and AT ends differed by 0.6 kcal/mol. Electron microscopic
      analysis demonstrated that the majority of Holliday junctions harbor the cross
      point within a 300 base pair region of the fragment ends. This insight into the
      mechanism of homologous duplex interaction extends our understanding of different
      DNA rearrangements. Understanding of DNA-DNA interaction is of practical use for
      better interpretation and optimization of PCR-based analyses.

PMID- 12056912
TI  - Nucleoplasmin interaction with protamines. Involvement of the polyglutamic tract.
AB  - Different recombinant forms of nucleoplasmin including truncations at the
      carboxyl-terminal end of the molecule (r-NP121, r-NP142) have been expressed and
      purified. All of them were found to oligomerize, forming pentameric complexes
      which, according to their hydrodynamic properties, can be modeled by oblate
      ellipsoids of constant width. In this model, the highly charged carboxyl ends
      appear to be arranged around a pentameric core along the plane defined by the
      major axes of the ellipsoid. Importantly, all the recombinant forms appear to be
      able to decondense protamine-containing sperm nuclei. However, although the
      stoichiometry with which protamines bind to these forms appears to be constant
      (2.5 mol of protamine/mol of nucleoplasmin pentamer), the efficiency with which
      they remove protamines from the sperm DNA decreases in the following order: o-NP
      > r-NP142 > or = r-NP >> r-NP121. Therefore, the main polyglutamic tract of
      nucleoplasmin (which is absent in r-NP121), while enhancing the efficiency of
      protamine removal, is not indispensable for sperm chromatin decondensation in the
      biological model we have used.

PMID- 12056913
TI  - Spectroscopic properties of a mitochondrial cytochrome C with a single thioether
      bond to the heme prosthetic group.
AB  - The yeast iso-1-cytochrome c variant Cys14Ser has been prepared in which one of
      the two thioether bonds by which the heme prosthetic group is normally bound to
      the protein has been eliminated. Comparison of the properties of this variant
      with those of the wild-type cytochrome provides insight into the role of this
      covalent attachment of the heme group to the apo-protein toward the functional
      properties of the wild-type cytochrome. Although NMR and EPR spectra indicate
      that the Cys14Ser variant ferricytochrome adopts the native conformation
      characteristic of the wild-type protein with His18 and Met80 coordinated to the
      heme iron (Met80 epsilon-CH -23.6 ppm; g(z), g(y), g(x), at 3.01, 2.29,
      approximately 1.3, respectively), the electronic spectrum of the variant does not
      exhibit the 695 nm CT band that is characteristic of native ferricytochromes c
      with these axial ligands. Chromatographic and spectropolarimetric comparison of
      the variant and wild-type ferricytochromes suggests that the structure of the
      variant is more disordered, particularly in the region of the sole tryptophanyl
      residue (Trp59). Upon reduction, the electronic spectrum of the variant exhibits
      a symmetrically broadened alpha-band that is shifted approximately 3 nm to the
      ultraviolet relative to its position in the spectrum in the wild-type protein. In
      the MCD spectrum, a band appears above 390 nm that is more intense than the Soret
      A-term which is also shifted to lower energy.

PMID- 12056914
TI  - Binding of L-arginine and imidazole suggests heterogeneity of rat brain neuronal
      nitric oxide synthase.
AB  - Nitric oxide synthase (NOS) is inhibited by imidazole, which binds to the heme in
      a low-spin complex absorbing at 428 nm. Conversion by L-arginine of this complex
      into a high-spin species absorbing at 395 nm is a common method to determine the
      binding parameters of Arg. However, both Arg-competitive and noncompetitive
      inhibition of NOS by imidazole has been reported, and optical studies with
      neuronal NOS provided no evidence for imidazole affecting Arg binding. We
      investigated the cause for these paradoxical observations with recombinant rat
      brain neuronal NOS. Imidazole bound to nNOS with a K(d)(app) of 50 microM;
      tetrahydrobiopterin (BH4) lowered the affinity of nNOS for imidazole 4-fold. The
      enzyme behaved heterogeneously with respect to Arg binding. Most of nNOS (65-80%)
      showed competition between Arg and imidazole. In the presence of BH4, a K(d)(Arg)
      of 1 microM could be estimated for this fraction, as well as apparent association
      and dissociation rate constants of 2.5 x 10(6) M(-1) x s(-1) and 2.5 s(-1). A
      second fraction of nNOS (20-30%) exhibited little or no competition.
      Consequently, Arg binding did not cause dissociation of the imidazole complex for
      this fraction, and complete generation of the high-spin state by Arg could not be
      achieved in the presence of imidazole. A third fraction (< or =10%) bound Arg
      with low affinity (K(d) 1-2 mM). Because of this heterogeneity, titration curves
      with Arg became almost uninterpretable. We propose that this heterogeneous
      response of nNOS toward Arg and imidazole is underlying the apparently
      conflicting results reported in the literature.

PMID- 12056915
TI  - Electrostatic and hydrophobic forces tether the proximal region of the
      angiotensin II receptor (AT1A) carboxyl terminus to anionic lipids.
AB  - The carboxyl terminus of the type-1 angiotensin II receptor (AT(1A)) is a focal
      point for receptor activation and deactivation. Synthetic peptides corresponding
      to the membrane-proximal, first 20 amino acids of the carboxyl terminus adopt an
      alpha-helical conformation in organic solvents, suggesting that the secondary
      structure of this region may be sensitive to hydrophobic environments. Using
      surface plasmon resonance, immobilized lipid chromatography, and circular
      dichroism, we examined whether this positively charged, amphipathic alpha-helical
      region of the AT(1A) receptor can interact with lipid components in the cell
      membrane and thereby modulate local receptor attachment and structure. A
      synthetic peptide corresponding to the proximal region of the AT(1A) receptor
      carboxyl terminus (Leu(305) to Lys(325)) was shown by surface plasmon resonance
      to bind with high affinity to the negatively charged lipid, dimyristoyl L-alpha
      phosphatidyl-DL-glycerol (DMPG), but poorly to the zwitterionic lipid,
      dimyristoyl L-alpha-phosphatidylcholine (DMPC). In contrast, a peptide analogue
      possessing substitutions at four lysine residues (corresponding to
      Lys(307,308,310,311)) displayed poor association with either lipid, indicating a
      crucial anionic component to the interaction. Circular dichroism analysis
      revealed that both the wild-type and substituted peptides possessed alpha-helical
      propensity in methanol and trifluoroethanol, while the wild-type peptide also
      adopted partially inserted helical structure in DMPG and DMPC liposomes. In
      contrast, the substituted peptide exhibited spectra that suggested the presence
      of beta-sheet and alpha-helical structure in both liposomes. Immobilized lipid
      chromatography was used to characterize the hydrophobic component of the membrane
      interaction, and the results demonstrated that hydrophobic and electrostatic
      interactions mediated the binding of the wild-type peptide but that the
      substituted peptide bound to the model membranes mainly via hydrophobic forces.
      We propose that, in intact AT(1A) receptors, the proximal carboxyl terminus
      associates with the cytoplasmic face of the cell membrane via a high-affinity,
      anionic phospholipid-specific tethering that serves to increase the amphipathic
      helicity of this region. Such associations may be important for receptor function
      and common for G protein-coupled receptors.

PMID- 12056916
TI  - Characterization of a novel mammalian phosphatase having sequence similarity to
      Schizosaccharomyces pombe PHO2 and Saccharomyces cerevisiae PHO13.
AB  - p34, a specific p-nitrophenyl phosphatase (pNPPase) was identified and purified
      from the murine cell line EL4 in a screen for the intracellular molecular targets
      of the antiinflammatory natural product parthenolide. A BLAST search analysis
      revealed that it has a high degree of sequence similarity to two yeast alkaline
      phosphatases. We have cloned, sequenced, and expressed p34 as a GST-tagged fusion
      protein in Escherichia coli and an EE-epitope-tagged fusion protein in mammalian
      cells. Using p-nitrophenyl phosphate (pNPP) as a substrate, p34 is optimally
      active at pH 7.6 with a K(m) of 1.36 mM and K(cat) of 0.052 min(-1). Addition of
      1 mM Mg(2+) to the reaction mixture increases its activity by 14-fold. Other
      divalent metal ions such as Co(2+) and Mn(2+) also stimulated the activity of the
      enzyme, while Zn(2+), Fe(2+), and Cu(2+) had no effect. Furthermore, both NaCl
      and KCl enhanced the activity of the enzyme, having maximal effect at 50 and 75
      mM, respectively. The enzyme is inhibited by sodium orthovanadate but not by
      sodium fluoride or okadaic acid. Mutational analysis data suggest that p34
      belongs to the group of phosphatases characterized by the sequence motif
      DXDX(T/V).

PMID- 12056917
TI  - A kinetic approach for the study of protein phosphatase-catalyzed regulation of
      protein kinase activity.
AB  - The activities of many protein kinases are regulated by phosphorylation. The
      phosphorylated protein kinases thus represent an important class of substrates
      for protein phosphatases. However, our ability to study the phosphatase-catalyzed
      substrate dephosphorylation has been limited in many cases by the difficulty in
      preparing sufficient amount of stoichiometrically phosphorylated kinases. We have
      applied the kinetic theory of substrate reaction during irreversible modification
      of enzyme activity to the study of phosphatase-catalyzed regulation of kinase
      activity. As an example, we measured the effect of the hematopoietic protein
      tyrosine phosphatase (HePTP) on the reaction catalyzed by the fully activated,
      bisphosphorylated extracellular signal-regulated protein kinase 2 (ERK2/pTpY).
      Because only a catalytic amount of ERK2/pTpY is required, this method alleviates
      the need for large quantities of phospho-ERK2. Kinetic analysis of the ERK2/pTpY
      catalyzed substrate reaction in the presence of HePTP leads to the determination
      of the rate constants for the HePTP-catalyzed dephosphorylation of free ERK2/pTpY
      and ERK2/pTpY*substrate(s) complexes. The data indicate that ERK2/pTpY is a
      highly efficient substrate for HePTP (k(cat)/K(m) = 3.05 x 10(6) M(-1) s(-1)).
      The data also show that binding of ATP to ERK2/pTpY has no effect on ERK2/pTpY
      dephosphorylation by HePTP. In contrast, binding of an Elk-1 peptide substrate to
      ERK2/pTpY completely blocks the HePTP action. This result indicates that
      phosphorylation of Tyr185 is important for ERK2 substrate recognition and that
      binding of the Elk-1 peptide substrate to ERK2/pTpY blocks the accessibility of
      pTyr185 to HePTP for dephosphorylation. Collectively, the results establish that
      the kinetic theory of irreversible enzyme modification can be applied to study
      the phosphatase catalyzed regulation of kinase activity.

PMID- 12056919
TI  - Hypertension and hypercholesterolaemia as risk factors for Alzheimer's disease:
      potential for pharmacological intervention.
AB  - This paper focuses on hypertension and hypercholesterolaemia as risk factors for
      Alzheimer's disease and, as such, subjects for prevention. The long-term,
      prospective, population-based studies regarding the relationship between
      hypertension or hypercholesterolaemia and Alzheimer's disease, and the clinical
      studies regarding the association between antihypertensive or lipid-lowering
      medications and the risk of Alzheimer's disease, are reviewed. These studies
      provide evidence to suggest that elevated blood pressure and cholesterol levels
      earlier in life may have an important role in the development and expression of
      late-life Alzheimer's disease. Based on these data, we propose that proper, early
      interventions aimed at reducing these cardiovascular risk factors may have an
      impact on the future incidence and prevalence of Alzheimer's disease.

PMID- 12056920
TI  - Cognitive dysfunction in multiple sclerosis: natural history, pathophysiology and
      management.
AB  - Cognitive dysfunction is a major cause of disability in patients with multiple
      sclerosis (MS). The prevalence of cognitive dysfunction is estimated at 45 to
      65%. Natural history studies suggest that once cognitive dysfunction develops in
      a patient with MS, it is not likely to remit. Unlike physical disability in MS,
      cognitive disability correlates weakly with T2 lesion burden on brain magnetic
      resonance imaging (MRI). More robust correlations exist with magnetisation
      transfer imaging and MRI measures of brain atrophy. Patients with MS who have
      cognitive impairment most commonly display deficits in the cognitive domains of
      memory, learning, attention and information processing. In diagnosing cognitive
      dysfunction in a patient with MS, it is important first to recognise and treat
      the common comorbidities of fatigue and depression. The first step in the
      treatment of cognitive dysfunction is to delay disease progression, and there are
      currently five such disease-modifying agents approved for the treatment of MS
      (two preparations of interferon-beta-1a, interferon-beta-1b, glatiramer acetate
      and mitoxantrone). Nonpharmacological measures, such as cognitive rehabilitation,
      occupational therapy and psychotherapy, are the mainstays of symptomatic
      treatment. Pharmacological symptomatic therapy centres on the treatment of
      comorbid fatigue and depression. There are currently no effective pharmacological
      agents approved as symptomatic therapy of cognitive dysfunction in MS.

PMID- 12056921
TI  - Patients' subjective experiences of antipsychotics: clinical relevance.
AB  - The subjective experience of patients with schizophrenia who are receiving
      antipsychotic medication has been a neglected research area, as has the
      satisfaction of patients with their drug treatments. This is unfortunate, as
      satisfaction with treatment appears to be related strongly to the readiness of
      patients to take their medication as prescribed, and thereby to outcome.
      Patients' perceptions of their treatment do not appear to be related strongly to
      severity of illness or symptom ratings, although there are associations between
      perceptions of treatment and adverse effects. Surveys of patient experience with
      typical antipsychotics have tended to indicate high levels of dissatisfaction and
      perceived adverse effects. There have been a number of surveys of patients'
      perceptions of treatment with the atypical antipsychotics. These tend to accord
      with the expectation that a relative freedom from adverse effects with the
      atypical antipsychotics will be reflected in enhanced levels of satisfaction and
      perceived well-being. In general, these studies share a number of weaknesses,
      including small sample sizes, bias in selection of respondents, open treatment
      and lack of suitable comparator groups. In addition, many have adopted a cross
      sectional, rather than longitudinal, approach and have relied on nonvalidated and
      perhaps idiosyncratic rating measures. Recently, there have been studies of
      better methodological quality. These, too, have indicated that patients regard
      the newer treatments more positively than the older regimens. In addition, there
      is now evidence that the various new-generation antipsychotics may be evaluated
      differently by patients.

PMID- 12056922
TI  - Relapse and rehospitalisation rates in patients with schizophrenia: effects of
      second generation antipsychotics.
AB  - Recent studies suggest that the risk of relapse in patients with schizophrenia is
      approximately 3.5% per month. Predictors of more frequent relapses include poor
      compliance with antipsychotic drug treatment, severe residual psychopathology,
      poor insight into the illness and the need for treatment, comorbid substance
      abuse, and poor relationships between patients, families and care providers.
      Although conventional antipsychotic drugs, such as haloperidol and fluphenazine,
      are effective in preventing relapse, second generation antipsychotic drugs, such
      as clozapine, risperidone and olanzapine, appear to be superior in preventing
      relapse and improving the patient's quality of life. The development of adverse
      events can undermine treatment response and relapse prevention. Minimising
      adverse effects thus helps to improve treatment compliance and prevent relapse.
      Second generation antipsychotic drugs tend to have fewer adverse effects than
      conventional agents, especially pseudoparkinsonism and akathisia. The societal
      costs of treating patients with schizophrenia can be lessened by employing
      strategies that decrease relapse and the need for rehospitalisation, the most
      costly treatment alternative.

PMID- 12056924
TI  - Spotlight on almotriptan in migraine.
AB  - Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan').
      Its efficacy and tolerability have been assessed in a number of randomised,
      controlled trials in over 4800 adults with moderate or severe attacks of
      migraine. Oral almotriptan has a rapid onset of action (significant headache
      relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy
      is sustained in most patients who respond by 2 hours. The drug is significantly
      more effective than placebo as measured by a number of parameters including 2
      hour headache response and pain-free response rates. Other symptoms of migraine,
      including nausea, photophobia and phonophobia, are also alleviated by
      almotriptan. The efficacy of oral almotriptan appears to be maintained over
      repeated doses for multiple attacks of migraine treated over a long period (up to
      1 year). High headache response rates were reported over all attacks without
      tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan
      12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan
      report less concern with adverse effects than patients given sumatriptan. The
      lower incidence of chest pain following treatment with almotriptan than with
      sumatriptan may lead to a reduction in direct costs, with fewer patients
      requiring management of chest pain. Almotriptan is well tolerated. Most adverse
      events were of mild or moderate intensity, transient and generally resolved
      without intervention or the need for treatment withdrawal. The most common
      adverse events associated with oral almotriptan 12.5mg treatment were dizziness,
      paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and
      chest symptoms. The incidence of adverse events did not differ from placebo and
      decreased in the longer term. Almotriptan can be coadministered with drugs that
      share a common hepatic metabolic path; in addition, dosage reduction is required
      only in the presence of severe renal or hepatic impairment. CONCLUSIONS:
      Almotriptan is an effective drug for the acute treatment of moderate or severe
      attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown
      greater efficacy than placebo; current data indicate that efficacy is similar to
      that of oral sumatriptan 50mg, and is maintained in the long term (< or = 1
      year). Almotriptan has a good adverse event profile and a generally similar
      overall tolerability profile to sumatriptan; of note, almotriptan is associated
      with a significantly lower incidence of chest pain than sumatriptan. However,
      further clinical experience is required to clearly define the place of
      almotriptan among the other currently available triptans. Nevertheless, because
      triptans have an important place in various management regimens, and because the
      nature of individual patient response to triptans is idiosyncratic, almotriptan
      is likely to become a useful treatment option in the management of adults with
      moderate or severe migraine headaches.

PMID- 12056925
TI  - Through a glass, darkly: cerebrospinal fluid viral load measurements and the
      pathogenesis of human immunodeficiency virus infection of the central nervous
      system.

PMID- 12056926
TI  - The neurology of reasoning.

PMID- 12056923
TI  - Cholinergic nicotinic systems in Alzheimer's disease: prospects for
      pharmacological intervention.
AB  - Within the last few years, research into the cause and progression of Alzheimer's
      disease has made significant advances. Although there is still no preventative
      treatment or cure for this neurodegenerative illness, the development of drugs
      that may alleviate some of the cognitive symptoms associated with it is
      advancing. Cholinesterase inhibitors are at present the most effective form of
      treatment and have shown significant overall response rates in clinical trials.
      However, although some patients show substantial improvement when treated with
      this class of drugs, there is considerable variability in the amount of benefit
      gained in different individuals in terms of their cognitive and behavioural
      functioning. Furthermore, unfortunately some patients gain little or no benefit
      from these drugs. It would therefore be of great advantage to explore alternative
      therapeutic possibilities. This article reviews the potential involvement of the
      nicotinic cholinergic system in Alzheimer's disease and discusses the possibility
      of nicotinic pharmacotherapy. Substantial evidence indicates the involvement of
      the nicotinic cholinergic system in the pathology of Alzheimer's disease. Drugs
      targeting these sites may not only have a positive effect on cognitive function,
      but also have additional therapeutic benefits in terms of restoring the
      hypoactivity in the excitatory amino acid pyramidal system and even slowing the
      emergence of Alzheimer's disease pathology. The conclusion of this review is that
      nicotinic treatments are an important potential source of new therapeutic
      interventions in Alzheimer's disease.

PMID- 12056927
TI  - Progression to neuropsychological impairment in human immunodeficiency virus
      infection predicted by elevated cerebrospinal fluid levels of human
      immunodeficiency virus RNA.
AB  - BACKGROUND: If cerebrospinal fluid (CSF) human immunodeficiency virus (HIV) RNA
      levels are elevated before the development of neuropsychological (NP) impairment,
      such an observation would support prospective monitoring of CSF HIV RNA levels as
      well as therapeutic interventions designed to lower CSF HIV levels. OBJECTIVE: To
      determine whether increased CSF HIV RNA levels at an earlier time predict
      subsequent progression to NP impairment in HIV-infected subjects. METHODS: We
      examined 139 subjects in a prospective cohort study. Comprehensive NP,
      neuromedical, and laboratory evaluations were performed at initial and follow-up
      visits at least 6 months apart. Human immunodeficiency virus RNA levels in plasma
      and CSF were measured with a commercially available, polymerase chain reaction
      based assay. To assess the robustness of our findings, we analyzed changes in NP
      performance over time in 2 ways. First, we used masked clinical ratings of global
      NP performance to identify individuals who were initially NP normal, and then
      determined, in a similarly blinded fashion, which of these subjects subsequently
      became NP impaired. Second, in a separate analysis, we assessed change in
      subjects' raw scores on each of a series of NP test measures between baseline and
      follow-up. RESULTS: Among subjects who were not impaired at the initial visit,
      higher levels of HIV RNA in CSF significantly predicted progression to global NP
      impairment at the follow-up evaluation. Cerebrospinal fluid HIV RNA levels
      outperformed other clinical and laboratory measures in predicting progression to
      NP impairment. Higher CSF HIV RNA levels were associated with worsening
      performance on tests of attention, learning, and motor function. CONCLUSION:
      Because elevated CSF HIV RNA levels (>or=200 copies/mL) predict subsequent
      progression to NP impairment, monitoring of CSF viral load and therapy to reduce
      CSF HIV RNA levels may be clinically warranted, even if impairment is not
      identified at the time of lumbar puncture.

PMID- 12056928
TI  - Active human herpesvirus 6 infection in patients with multiple sclerosis.
AB  - CONTEXT: Human herpesvirus 6 (HHV-6) has been linked with multiple sclerosis
      (MS). OBJECTIVES: To determine HHV-6 viral load in patients with MS, and to
      analyze separately its 2 variants, HHV-6A and HHV-6B. PATIENTS AND METHODS: We
      analyzed 149 blood and serum samples; 103 were from patients with relapsing
      remitting MS (33 during an MS relapse and 70 during remission), and 46 were from
      healthy blood donors. To determine whether the HHV-6 genome and its variants were
      present, we analyzed viral DNA using quantitative real-time polymerase chain
      reaction, which has a sensitivity of 1 copy. RESULTS: We found HHV-6 DNA in the
      peripheral blood mononuclear cells of 53.4% of patients and 30.4% of healthy
      blood donors; HHV-6A was found in 20.4% of patients and 4.4% of controls, and HHV
      6B was found in 33.0% vs 26.1%, respectively. Mean viral load in both groups was
      7.4 copies of HHV-6 per microgram of DNA (range, 1-15 copies). Analysis of serum
      samples showed that none of the healthy blood donors were positive for HHV-6,
      although 14.6% of patients were positive for the virus, specifically the HHV-6A
      variant. There was no difference between patients during remission or relapse.
      Mean viral load was 26.3 copies/microg microgram of DNA (range, 1-86 copies).
      CONCLUSIONS: Despite the low viral load and the lack of clinical correlation, and
      given the biological characteristics of the virus, our results suggest that there
      was active HHV-6A infection in 14.6% of patients with MS. Further quantitative
      real-time polymerase chain reaction studies will help us understand the clinical
      significance of such a low viral load.

PMID- 12056929
TI  - Association between the extended tau haplotype and frontotemporal dementia.
AB  - BACKGROUND: Recent studies have shown an association between an extended tau
      haplotype (H1) that covers the entire human tau gene and progressive supranuclear
      palsy or, more inconsistently, other neurodegenerative disorders, such as
      corticobasal degeneration, Parkinson disease, Alzheimer disease, and
      frontotemporal dementia (FTD). In addition, disease-causing mutations in the tau
      gene on chromosome 17 have been detected in some families with autosomal dominant
      FTD and parkinsonism. In FTD, the pathological accumulation of the microtubule
      associated protein tau suggests that the tau gene may be a genetic risk factor
      for this disorder. OBJECTIVE: To confirm or refute the association between the H1
      haplotype or the H1H1 genotype of the tau gene and FTD. DESIGN: Case-control
      study. SETTING: Neurology departments of 12 French university hospitals.
      PARTICIPANTS: One hundred unrelated patients with FTD and 79 controls. METHODS:
      Tau genotype (contiguous polymorphisms in exons 1, 7, and 13 and in intron 9 used
      to reconstruct the extended haplotypes H1 and H2). Clinical examination,
      psychometric testing, laboratory tests, computed tomography and magnetic
      resonance imaging, single-photon emission computed tomography, and
      electroencephalography for patients with FTD. RESULTS: The H1H1 genotype was
      significantly overrepresented in patients with FTD compared with controls (62% vs
      46%; P=.01, 1-sided; odds ratio adjusted for age and sex, 1.95). After
      stratification according to apolipoprotein E (APOE) genotype, we found a
      significant interaction between APOE and tau genotypes (P=.03). CONCLUSIONS: This
      study of the largest series of patients with FTD confirms the primary role of tau
      in FTD and establishes that the H1 haplotype of the tau gene and the E2 allele of
      APOE interact by an unknown mechanism that increases the risk of FTD.

PMID- 12056930
TI  - Clinical features and disease haplotypes of individuals with the N279K tau gene
      mutation: a comparison of the pallidopontonigral degeneration kindred and a
      French family.
AB  - BACKGROUND: An N279K missense mutation in exon 10 of the tau gene reported in an
      American family with pallidopontonigral degeneration (PPND family) was recently
      found in members of a French kindred with dementia and supranuclear palsy.
      OBJECTIVES: To compare clinical phenotypes of both families and to perform
      genealogical and molecular genetic studies to determine whether they are derived
      from a common founder. DESIGN AND METHODS: We performed clinical examinations of
      affected members of both families and compared clinical phenotypes, existing
      genealogical family records, and chromosome 17 microsatellite repeat markers in
      the vicinity of the tau gene. RESULTS: The inheritance pattern is autosomal
      dominant in the PPND family and appears so in the French family. Average age at
      onset of clinical symptoms was 43 years in the PPND family and 41 years in the
      French family. Mean disease duration was 8 years in the PPND family and 6 years
      in the French family. Parkinsonism, personality changes, and dementia of the
      frontotemporal type were seen in both kindreds. All affected patients exhibited
      rapidly progressive parkinsonism characterized by bradykinesia, tremor, postural
      instability, and rigidity. Some had a transient response to levodopa therapy
      during the initial stages. Pyramidal signs and eye movement abnormalities,
      including supranuclear gaze palsy, were common. Results of linkage studies of the
      tau region in chromosome 17 did not reveal a haplotype common to both kindreds.
      CONCLUSIONS: Affected members from both families had more clinical similarities
      than differences. Results of genealogical and molecular genetic studies
      determined that the families were not related. The N279K mutations found in both
      families have independent origins.

PMID- 12056931
TI  - Correlation of regional proton magnetic resonance spectroscopic metabolic changes
      with cognitive deficits in mild Alzheimer disease.
AB  - CONTEXT: The staging of Alzheimer disease (AD) dementia could be improved by a
      neurometabolic analysis using magnetic resonance spectroscopy. OBJECTIVE: To
      examine the correlation between regional cerebral metabolic alterations measured
      by proton magnetic resonance spectroscopy and neuropsychological dysfunctions in
      patients with early AD. DESIGN: A case-control study. SETTING: University
      hospital neurology clinic and radiology department. PARTICIPANTS: A cohort of 14
      patients with mild AD and 14 control subjects paired for age and sex.
      INTERVENTIONS: Single-voxel proton magnetic resonance spectroscopic brain
      examination (60 minutes) and a comprehensive battery of psychometric tests (2
      hours). MAIN OUTCOME MEASURES: Metabolite ratios relative to unsuppressed water
      were calculated for magnetic resonance spectroscopic metabolites (N
      acetylaspartate, choline, creatine-phosphocreatine, and myo-inositol) in the
      medial temporal lobes (MTLs), parietotemporal cortices (PTCs), and frontal
      cortices of both hemispheres. Correlations were examined between metabolic
      changes in an area and psychometric scores of its known regional function: MTL
      and verbal memory, PTC and language and visuoconstructional abilities, and
      frontal cortices and executive functions. RESULTS: A significant reduction of N
      acetylaspartate/water (H2O) in the left MTL and of choline/H2O in both MTLs, as
      well as a significant increase of myo-inositol/H2O in the right PTC were
      observed. Metabolic alterations in the left MTL were correlated with a loss of
      verbal memory, in the left PTC with language impairment, and in the right PTC
      with a loss of visuoconstructional abilities in the group with AD. CONCLUSION:
      These findings are consistent with regional distribution of neuropathologic
      changes and cognitive symptoms characterizing early phases of AD, and with the
      pattern of lateralization of normal brain function.

PMID- 12056932
TI  - Molecular findings in familial Parkinson disease in Spain.
AB  - BACKGROUND: Several genetic errors in alpha-synuclein (Park1) and ubiquitin
      carboxyl-terminal-hydrolase L1(Park5) genes cause autosomal dominant familial
      Parkinson disease. Mutations in the parkin gene (Park2) are the major cause of
      autosomal recessive Parkinson disease. OBJECTIVE: To analyze the clinical and
      molecular data of 19 Spanish kindreds (13 with recessive, 4 with dominant, and 2
      with uncertain inheritance) who have familial Parkinson disease. METHODS: We
      searched for the previously described mutations in Park1 and Park5 genes and for
      new or described mutations in Park2. We used single-strand conformation
      polymorphism, direct sequencing, and restriction digestion of polymerase chain
      reaction (PCR)-amplified genomic DNA for this study. RESULTS: None of these
      families have either Park1 or Park5 mutations. We found 5 different mutations in
      Park2 gene in 5 of the families with recessive inheritance. To our knowledge, 2
      of these mutations, V56E and C212Y, have not been previously reported. The other
      mutations found (deletion of exons 3 and 5 and 225delA) have been described in
      other ethnic groups. Heterozygous carriers of a single Park2 mutation either were
      asymptomatic or developed clinical symptoms in late adulthood or after brief
      exposure to haloperidol therapy. CONCLUSIONS: Mutations in Park2 gene account for
      38% of the families with recessive parkinsonism in Spain. We found 2 cases of
      simple heterozygous Park2 mutation carriers that developed clinical symptoms,
      either in late adulthood or after brief exposure to parkinsonizing agents. Thus,
      hereditary Parkinson disease has more variable clinical phenotype and molecular
      defects than previously thought since heterozygous mutations could be a risk
      factor for parkinsonism.

PMID- 12056933
TI  - Increase of brain oxidative stress in mild cognitive impairment: a possible
      predictor of Alzheimer disease.
AB  - BACKGROUND: The isoprostane 8,12-iso-iPF(2alpha)-VI, a specific marker of in vivo
      lipid peroxidation, is increased in Alzheimer disease (AD). The pathological
      changes associated with AD have a long silent phase before the appearance of
      clinical symptoms. Several studies have shown that AD is preceded by a prodromal
      phase characterized by mild cognitive impairment (MCI). OBJECTIVE: To investigate
      levels of this biomarker in subjects with MCI. DESIGN AND MAIN OUTCOME MEASURES:
      Using gas chromatography-mass spectrometry analysis, we measured 8,12-iso
      iPF(2alpha)-VI levels in urine, plasma, and cerebrospinal fluid of patients with
      AD, subjects with MCI, and cognitively normal elderly subjects. SETTING AND
      PATIENTS: Subjects attending the Memory Disorders Clinic. RESULTS: We found
      significantly higher 8,12-iso-iPF(2alpha)-VI levels in cerebrospinal fluid,
      plasma, and urine of subjects with MCI compared with cognitively normal elderly
      subjects. CONCLUSIONS: These results imply that individuals with MCI have
      increased brain oxidative damage before the onset of symptomatic dementia.
      Measurement of this isoprostane may identify a subgroup of patients with MCI with
      increased lipid peroxidation who are at increased risk to progress to symptomatic
      AD.

PMID- 12056934
TI  - Spontaneous intracranial internal carotid artery dissection: report of 10
      patients.
AB  - BACKGROUND: Spontaneous intracranial internal carotid artery (ICA) dissection is
      an uncommon cause of cerebral infarction, particularly when compared with the
      dissection of the ICA's cervical portion. Most reports describe extensive strokes
      with very high mortality rates. OBJECTIVE: To report the clinical and
      radiological findings of 10 patients with spontaneous intracranial ICA
      dissection. METHODS: Ten patients (5 women) were included with ages ranging from
      15 to 59 years (mean age, 28 years). RESULTS: Nine patients had a stroke (1 had
      an associated subarachnoid hemorrhage), whereas 1 patient had only transient
      ischemic attacks. Severe retro-orbital or temporal headache followed by
      contralateral hemiparesis was the most common initial clinical symptom. No
      patient had vascular risk factors or a history of neck or head trauma. Stenosis
      of the supraclinoid portion of the ICA occurred in 8 patients, with extension to
      the middle cerebral artery or anterior cerebral artery in 2 patients each.
      Aneurysm formation in the ipsilateral anterior cerebral artery was seen in 1
      patient. Two patients had a total occlusion of the supraclinoid portion of the
      ICA. All patients did well, with no (n = 3), mild (n = 4), or moderate (n = 3)
      disability on the Modified Rankin Scale during a 3-month follow-up period.
      CONCLUSIONS: Spontaneous intracranial ICA dissection can cause ischemic stroke
      with or without subarachnoid hemorrhage and should be considered in the
      differential diagnosis of intracranial ICA stenosis or occlusion, especially in
      young patients. Some patients survive with few or moderate deficits.

PMID- 12056935
TI  - Contributions of dopaminergic drugs and disease severity to daytime sleepiness in
      Parkinson disease.
AB  - BACKGROUND: Excessive daytime somnolence is a common report among patients who
      have Parkinson disease (PD). The relative contributions of disease severity and
      of the various dopaminergic drugs are unclear. OBJECTIVE: To separate and
      quantify the contributions of disease markers and drug doses. METHODS: Patients
      seen during a 7-month period at a center for movement disorders completed the
      Epworth Sleepiness Scale. Treatment subgroups were compared. The relationship to
      sedation of age; dopaminergic drug classes and doses; Hoehn and Yahr stage;
      duration of disease; total score on the motor subsection of the Unified Parkinson
      Disease Rating Scale; and the presence or absence of dementia, depression, or
      hallucinations was calculated using simple and multiple regression and t tests.
      RESULTS: The Epworth Sleepiness Scale scores were higher among patients with PD
      (mean [SD], 10.8 [5.3]; n = 368) compared with patients with other neurological
      disorders (mean, 8.5 [5.1]; n = 243; P<.001). A model containing the Hoehn and
      Yahr stage, levodopa dose, and use of a dopamine agonist was the best at
      predicting the total score of Epworth Sleepiness Scale in patients who have PD,
      but accounted for only 9% of the interindividual variance. The parameter
      estimates (SE) corresponded to a 1.02 (0.03)-point increase per Hoehn and Yahr
      stage, a 0.14 (0.06)-point increase per 100-mg increase in levodopa dose over 24
      hours, and a 2.33 (0.57)-point increase with use of an agonist. There was no
      statistically significant dose response for agonists. No statistically
      significant difference in sedation among the commonly used dopamine agonists was
      found. CONCLUSIONS: Somnolence in patients with PD, which is on average 25%
      higher than in other neurological diseases, is related to PD stage, levodopa
      dose, and the use of a dopamine agonist. However, most of the variability in
      sedation levels in patients with PD as well as in controls is the result of, as
      yet, unidentified factors.

PMID- 12056936
TI  - Intranasal civamide for the treatment of episodic cluster headaches.
AB  - OBJECTIVE: To evaluate the safety and efficacy of intranasal civamide solution
      for preventive treatment during an episodic cluster headache period. SUBJECTS AND
      METHODS: This was a multicenter, double-blind, randomized, vehicle-controlled
      study with a 7-day treatment period and a 20-day posttreatment period performed
      at 14 headache/neurology centers in the United States. Twenty-eight subjects were
      randomized to receive civamide or its vehicle in a 2:1 ratio; 18 received
      civamide and 10 received the vehicle. Subjects received 100 microL of 0.025%
      civamide (25 microg) or 100 microL of the vehicle to each nostril via dropper
      once daily for 7 days. The total daily dose of civamide was 50 microg. MAIN
      OUTCOME MEASURES: The number of cluster headaches per week during the treatment
      and posttreatment periods, pain intensity, presence of associated symptoms, and
      the incidence of adverse events were assessed. RESULTS: Subjects in the civamide
      group had a significantly greater percent decrease in the number of headaches
      from baseline to posttreatment during days 1 through 7 (-55.5% vs -25.9%; P =.03)
      and a trend toward significance during days 8 through 14 (-66.9% vs -32.3%; P
      =.07) and days 15 through 20 (-70.6% vs -34.9%; P =.07), as well as a near
      significant decrease during the entire posttreatment period (days 1 through 20 [P
      =.054]) compared with the vehicle group. There were larger decreases in the
      number of headaches per week during the posttreatment period in the civamide
      treated group, with trends toward significance during posttreatment days 8
      through 14 (-8.6 vs -3.6; P =.09) and days 15 through 20 (-8.9 vs -3.6; P =.07).
      There were no significant differences between groups in cluster headache pain
      intensity, number of severe headaches, or associated symptoms. The most common
      adverse events included nasal burning (14 of 18 civamide-treated subjects, 1 of
      10 vehicle-treated subjects; P =.001) and lacrimation (9 of 18 civamide-treated
      subjects, 0 of 10 vehicle-treated subjects; P =.01). CONCLUSION: Intranasal
      civamide solution at a dose of 50 microg may be modestly effective in the
      preventive treatment of episodic cluster headache.

PMID- 12056937
TI  - Echogenicity of the substantia nigra: association with increased iron content and
      marker for susceptibility to nigrostriatal injury.
AB  - BACKGROUND: Patients with Parkinson disease characteristically exhibit an
      increased echogenicity of the substantia nigra (SN) on transcranial sonography, a
      new neuroimaging technique. The same echo feature of the SN can be identified in
      9% of healthy adults. OBJECTIVE: To evaluate the relevance of the echogenic SN in
      healthy adults. DESIGN: In the first part of the study, 10 healthy subjects
      younger than 40 years with a distinct SN hyperechogenicity underwent extensive
      neurological, motor, neuropsychological, and fluorine 18-dopa positron emission
      tomographic ([18F]-dopa PET) examinations. Results were compared with those of 10
      subjects with a low echogenic SN. In the second part of the study, the postmortem
      brains of 20 patients without extrapyramidal disorders during their lifetime were
      sonographically examined with a particular focus on SN echogenicity.
      Subsequently, one half of the brain was prepared for heavy metal analysis, the
      other for a histological examination. RESULTS: Healthy subjects with SN
      hyperechogenicity exhibited a significant reduction of the [18F]-dopa uptake,
      especially in the putamen (Wilcoxon matched pair test: left side, P =.006; right
      side, P =.009), whereas their neuropsychological and motor performance were
      normal. Postmortem studies showed that the echogenicity of the SN correlated with
      its iron content. CONCLUSIONS: Increased echogenicity of the SN,
      characteristically seen in Parkinson disease, is related to a functional
      impairment of the nigrostriatal system (even in young healthy adults) that can be
      revealed by [18F]-dopa PET studies. Substantia nigra hyperechogenicity is related
      to a higher tissue iron level, which is known to enhance the cells' generation of
      reactive oxygen specimens. Therefore, we hypothesize that transcranial sonography
      may identify a susceptibility marker for the development of nigral injury that
      can be detected early in life, prior to the onset of Parkinson disease.

PMID- 12056938
TI  - Acquired sexual paraphilia in patients with multiple sclerosis.
AB  - BACKGROUND: Sexual dysfunction in patients with multiple sclerosis is typically
      characterized by diminished libido, erectile and ejaculatory dysfunction in men,
      and poor lubrication and anorgasmy in women. In contrast, hypersexual behavior
      and paraphilias are distinctly uncommon in this population of patients, but have
      been associated with various focal brain lesions. PATIENT AND METHODS: We
      describe a man with clinically definite multiple sclerosis who developed profound
      and abrupt disinhibition and paraphilic behavior during an exacerbation. RESULTS:
      Neuroimaging revealed a marked increase in the number of enhancing lesions in the
      right sides of the hypothalamus and mesencephalon and extending into the right
      sides of the red nucleus, substantia nigra, and internal capsule. The altered
      sexual behavior was characterized by an obsessive and insatiable desire to touch
      women's breasts. CONCLUSIONS: Acquired sexual paraphilic behavior is uncommon in
      patients with multiple sclerosis but may occur when inflammatory demyelination
      involves the hypothalamic and septal regions of the basal prosencephalon. Our
      experience with this man illustrates the great difficulty involved in treating
      such patients when the paraphilic behavior becomes persistent.

PMID- 12056939
TI  - Complex neurologic syndrome associated with the G1606A mutation of mitochondrial
      DNA.
AB  - OBJECTIVES: To confirm the pathogenicity of the G-to-A substitution at nucleotide
      1606 (G1606A) mutation in the mitochondrial DNA (mtDNA) tRNA(Val) gene, and to
      characterize genotype-phenotype correlation. PATIENT AND METHODS: A 37-year-old
      man since childhood developed a complex clinical picture characterized by hearing
      loss, migraine, ataxia, seizures, cataracts, retinitis pigmentosa, mental
      deterioration, and hypothyroidism. Magnetic resonance imaging revealed diffuse
      calcification of the basal ganglia and cerebral cortical atrophy. Morphologic and
      biochemical studies of respiratory chain complexes were performed in skeletal
      muscle. All 22 mitochondrial tRNA genes were screened for mutations by direct
      sequencing. RESULTS: Biochemical analysis showed normal activities of respiratory
      chain enzymes and citrate synthase; morphologic examination showed scattered
      ragged-red fibers and poor or absent cytochrome c oxidase staining in 10% of the
      fibers. A heteroplasmic G1606A transition in the mtDNA tRNA(Val) gene was found.
      Mutant DNA was 70% of the total in the proband's muscle. The mutation was absent
      in blood samples and urinary sediment from his healthy brother and mother.
      CONCLUSION: This second patient with the G1606A mutation confirms both the
      pathogenicity of the mutation and its association with a characteristic complex
      neurologic phenotype.

PMID- 12056940
TI  - Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with
      sporadic hemiplegic migraine.
AB  - BACKGROUND: Familial hemiplegic migraine is a rare autosomal dominant subtype of
      migraine with aura that in half of the families is caused by mutations in the
      CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is,
      hemiplegic migraine without affected family members, the contribution of the
      CACNA1A gene is unknown. OBJECTIVE: To investigate the involvement of the CACNA1A
      calcium channel subunit gene in SHM. METHODS: We screened 27 patients with SHM
      for mutations in the CACNA1A gene by a combination of single-strand
      conformational polymorphism analysis and sequence analysis. RESULTS: One patient
      with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed
      tomography and carried a T666M mutation. Another patient with SHM who had no
      cerebellar signs carried an R583Q mutation. No mutations or interictal
      neurological abnormalities were found in the remaining 25 patients with SHM.
      CONCLUSIONS: Most patients with SHM do not have a CACNA1A mutation. The results
      of this study, combined with the findings reported in the literature, show that
      the presence of cerebellar symptoms in addition to the hemiplegic attacks
      increases the chance of finding a CACNA1A mutation. In addition, to our
      knowledge, we have found a first patient with SHM without cerebellar signs with a
      mutation.

PMID- 12056941
TI  - Diagnosis of cerebral venous thrombosis with echo-planar T2*-weighted magnetic
      resonance imaging.
AB  - BACKGROUND: Magnetic resonance (MR) signal changes suggestive of cerebral venous
      thrombosis (CVT) on T1- and T2-weighted images may be subtle and their
      identification requires a high degree of suspicion. Magnetic resonance venography
      remains essential for definitive diagnosis. Recent reports have shown that T2(*)
      weighted MR sequence is more sensitive than T1-weighted, T2-weighted, and fluid
      attenuated inversion recovery (FLAIR) images in detecting subarachnoid and
      intracerebral hemorrhages, both of which can be seen in association with CVT. The
      value of T2*-weighted magnetic resonance imaging (MRI) in diagnosing CVT has not
      been well studied. OBJECTIVES: To investigate and describe T2*(susceptibility
      weighted) MRI findings in 5 patients with CVT. METHODS: We reviewed our stroke
      database from May 1, 1997, through May 31, 2001. The diagnosis of CVT was made in
      6 patients, 5 had an MRI with T2* sequence. We examined T2*/susceptibility
      weighted images for these 5 patients to determine their ability, relative to T1
      weighted, T2-weighted, and FLAIR sequences, to detect CVT. RESULTS: On T2*
      weighted images, we were able to detect areas of hypointensities in the affected
      veins and/or sinuses in all 5 patients. Thrombosed veins and/or sinuses were more
      easily seen on T2*-weighted images than on any other MR sequence. The T2*
      sequence also allowed visualization of associated hemorrhagic venous infarcts,
      which were considerably less obvious on other MR sequences. CONCLUSIONS: The T2*
      weighted MR sequence can be useful in rapid detection of CVT and may enable the
      diagnosis to be made prior to MR venography. This is particularly important in
      clinically unsuspected patients, in whom MR venography is rarely obtained.

PMID- 12056943
TI  - Hemicrania continua.

PMID- 12056942
TI  - Spontaneous intracranial hypotension.

PMID- 12056944
TI  - Free standing: social control and the sane epileptic, 1850-1950.

PMID- 12056946
TI  - Hippocampal sclerosis and other hippocampal abnormalities in the early
      identification of candidates for epilepsy surgery.

PMID- 12056948
TI  - Lewy body disease.

PMID- 12056950
TI  - The use of quantitative methods in clinical trials for spinocerebellar ataxia.

PMID- 12056952
TI  - Denileukin diftitox for the treatment of panniculitic lymphoma.

PMID- 12056954
TI  - Healing from the inside out: one person's path with cutaneous T-cell lymphoma-
      mycosis fungoides.

PMID- 12056953
TI  - Aggressive immunosuppressive therapy for a refractory case of IgA pemphigus.

PMID- 12056955
TI  - Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV
      induced skin cancer: a study in the hairless mouse model.
AB  - OBJECTIVE: To assess the preventive effect of a cyclooxygenase 2 inhibitor,
      celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in
      hairless mice. DESIGN: Randomized dose-response study. A total of 75 SKH-HR-1
      female hairless mice, aged 2 months, were randomized into control, low-dose (200
      mg twice daily human dose equivalent), and high-dose (400 mg twice daily human
      dose equivalent) celecoxib treatment groups. Animals received 1 J/cm(2) daily (5
      d/wk) total irradiation. The animals were evaluated weekly for appearance of
      tumors, and the data were analyzed with respect to tumor latency period and tumor
      multiplicity using statistical software and Wilcoxon rank sum analyses,
      respectively. Prostaglandin E(2) levels in the blood and skin were assessed in
      each group. SETTING: Veterans Affairs Medical Center, Research and Dermatology
      Services. INTERVENTION: Animals received restricted diets containing the Food and
      Drug Administration-approved human equivalent doses of 200 mg (low dose) and 400
      mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were
      induced in all animals with an equivalent UV dose. MAIN OUTCOME MEASURES: Animals
      were evaluated weekly for the appearance of tumors, and data were analyzed with
      regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin
      E(2) levels in blood and epidermis were assessed in each group. RESULTS: Low
      doses and high doses of celecoxib significantly lengthened the tumor latency
      period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005
      and P<.001, respectively) compared with controls. There were no differences in
      the constitutive levels of blood or epidermal prostaglandin E(2) in the low- or
      high-dose treated animals compared with controls when analyzed at study
      termination. CONCLUSIONS: Celecoxib is an effective and safe chemopreventive
      agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of
      the influence of celecoxib on cancer incidence and its low association with
      systemic adverse effects have led to a potentially new therapeutic approach for
      the prevention of skin cancer.

PMID- 12056956
TI  - Aggressive squamous cell carcinomas in persons infected with the human
      immunodeficiency virus.
AB  - OBJECTIVES: To illustrate the potential for aggressive growth of cutaneous
      squamous cell carcinomas (SCCs) in patients infected with the human
      immunodeficiency virus (HIV) and to determine the factors associated with
      increased morbidity and mortality from aggressive SCCs in HIV-infected patients.
      DESIGN: Retrospective nonrandomized case series. SETTING: University-based
      dermatologic referral center. PATIENTS: A consecutive sample of 10 patients
      infected with HIV who had "aggressive" SCC based on the following criteria:
      diameter larger than 1.5 cm, rapid growth rate, local recurrence, and/or evidence
      of metastasis. MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Five
      patients died of metastatic SCC within 7 years of their initial diagnosis despite
      treatment. Human immunodeficiency virus stage and the degree of immunosuppression
      were not associated with increased morbidity and mortality. Patients initially
      undergoing combination surgery and radiation therapy or radical neck dissection
      had the best outcomes. CONCLUSIONS: Patients infected with HIV can develop
      rapidly growing cutaneous SCCs at a young age, with a high risk of local
      recurrence and metastasis. High-risk SCCs should be managed aggressively and not
      palliatively in patients infected with HIV.

PMID- 12056958
TI  - Sun protection policies and environmental features in US elementary schools.
AB  - OBJECTIVE: To assess current sun protection policies and the receptiveness to new
      policies at elementary schools in the United States. DESIGN: A cross-sectional
      telephone survey. SETTING: General educational community. PATIENTS OR OTHER
      PARTICIPANTS: In 1998, a random sample of 1000 public elementary schools in the
      United States was selected (proportional to population size) from 27 metropolitan
      areas chosen from the 58 US cities regularly reporting the UV index in 1997. A
      final sample of principals from 412 elementary schools completed the survey.
      INTERVENTION: None. MAIN OUTCOME MEASURES: Only 3.4% of schools had a sun
      protection policy. The most common reasons for not having a policy included the
      principal's lack of awareness (n = 113) or organizational barriers in the school
      districts (n = 77). Most principals (84.2%) said that students were outdoors
      during midday hours. Many principals (48.3%) were willing to adopt a sun
      protection policy. Most schools (72.8%) had shade structures but the majority
      (67.3%) reportedly covered less than one fifth of the grounds. Most principals
      (76.4%) were willing to increase the amount of shade structures. CONCLUSIONS: The
      low frequency of sun protection policies and shade structures calls for national
      efforts to change policies and environments to increase sun protection at US
      schools. Research is needed to demonstrate the efficacy of these changes.

PMID- 12056957
TI  - Altered clinical course of malignant melanoma in HIV-positive patients.
AB  - OBJECTIVE: To determine whether the natural history of melanoma is different in
      patients who test positive for human immunodeficiency virus (HIV) compared with
      matched control subjects. DESIGN: Retrospective cohort analysis. SETTING:
      Ambulatory care at 2 university-affiliated medical centers. PATIENTS: Each HIV
      positive melanoma patient (n = 17) was randomly matched with 2 HIV-negative
      patients (HIV status unknown, but without risk factors for HIV) based on the
      melanoma subtype, tumor thickness, Clark level, tumor location, and sex and age
      of the patient. MAIN OUTCOME MEASURES: Disease-free survival and overall survival
      of HIV-positive and HIV-negative melanoma patients were compared using a matched
      pairs analysis. CD4 cell counts were recorded at the time of melanoma diagnosis
      and disease recurrence. RESULTS: Melanoma patients who were HIV positive had a
      significantly shorter disease-free survival (P =.03) and overall survival (P
      =.045) compared with HIV-negative melanoma patients by matched-pairs analysis.
      There was an inverse relationship between CD4 cell counts and time to first
      melanoma recurrence. CONCLUSIONS: The natural history of malignant melanoma in
      HIV-positive patients is more aggressive compared with matched HIV-negative
      melanoma patients. Altered immune response and comorbid disease may play a role
      in the poor clinical outcome of HIV-positive patients. These findings have
      important implications in the management of melanoma in the setting of HIV
      disease.

PMID- 12056959
TI  - Product-related emphasis of skin disease information online.
AB  - BACKGROUND: In 2000, 41 million people searched for medical information online.
      The quality of that information is unregulated, variable, and not well studied.
      OBJECTIVE: To quantify and compare the numbers and types of Internet sites
      matched for 10 diverse skin conditions through different search systems. DESIGN:
      Search strategies were performed at 6-month intervals via Netscape Navigator,
      using 3 search engines and 1 directory. Ten skin conditions were chosen to
      represent common (psoriasis and eczema), cosmetic (wrinkles and cellulite),
      difficult-to-treat (alopecia, mastocytosis, granuloma annulare, and xanthoma),
      and uncommon (dermatitis herpetiformis and epidermolysis bullosa) problems.
      Search strings were designed to generate lists of Web sites that provide
      educational or product-related information. Results were compared. SETTING: The
      Saint Louis University information technology server, July 9, 1999, December 16,
      1999, and February 5, 2000. MAIN OUTCOME MEASURES: Comparisons of the total
      number, top 10 ranking, and type (educational vs product-related) of sites that
      matched through different search systems at 6-month intervals. RESULTS: The total
      number of matched sites for different skin conditions varied up to 100-fold. This
      number increased by 30% to 316% between July and December 1999. The largest
      number of Web sites related to wrinkles, followed by Web sites related to common
      conditions. Product-related sites outnumbered educational sites, especially for
      common and cosmetic conditions. Although there were differences in the total
      number of sites found through different search engines, the ratios of product
      related to educational sites were similar. Different search engines yielded
      different top 10 match lists for the same condition. The top 10 lists included
      higher proportions of educational sites than the total match lists for all
      conditions except cellulite. Within the top 10 lists, the rank order of well
      respected sites varied by search engine used and changed over time. CONCLUSIONS:
      Patients are increasingly accessing the growing body of data available through
      the Internet. Most Web sites contain information related to products. Until
      standards are enacted to govern the distribution of online medical information,
      consumers are at risk for obtaining misinformation and buying ineffective
      products. To better guide patients, physicians must become familiar with this
      ever-changing information.

PMID- 12056960
TI  - Regression of urticaria pigmentosa in adult patients with systemic mastocytosis:
      correlation with clinical patterns of disease.
AB  - OBJECTIVE: To determine clinical correlates of urticaria pigmentosa (UP)
      regression in adult patients with systemic mastocytosis (SM). DESIGN: Cohort
      study of the natural history of mastocytosis. SETTING: National Institutes of
      Health Clinical Center. PATIENTS: In a study of adult patients referred to the
      National Institutes of Health after 1980 and observed for a minimum of 10 years,
      12 of 106 adult patients experienced clearance or fading of UP. MAIN OUTCOME
      MEASURES: Data from each patient's history and results of physical examination,
      laboratory evaluation, and organ biopsy at presentation to the National
      Institutes of Health were compared with findings at the patient's most recent
      visit. RESULTS: In the patients in whom clearance of (n = 5) or a decrease in
      skin lesions (n = 7) was noted, UP had persisted from 4 to 34 years (median, 17
      years). Older age was a prognostic feature for regression of UP. Despite
      improvement of UP, the 2 patients with SM with an associated hematologic disorder
      experienced a deterioration in clinical condition. In the 10 patients with
      indolent SM, severity and frequency of symptoms decreased as the UP regressed.
      However, bone marrow changes consistent with SM remained. CONCLUSIONS: Urticaria
      pigmentosa regresses in approximately 10% of the older patients who have SM. In
      patients with an associated hematologic disorder such as myelodysplasia, this
      regression may be accompanied by disease progression. In contrast, regression of
      UP in patients with indolent SM parallels a decrease in disease intensity,
      although bone marrow findings of indolent SM remain.

PMID- 12056961
TI  - Mediation of systemic vascular hyperpermeability in severe psoriasis by
      circulating vascular endothelial growth factor.
AB  - BACKGROUND: Severe forms of psoriasis can be complicated by systemic
      microvascular hyperpermeability. Vascular endothelial growth factor (VEGF)
      possesses potent vascular permeability activity. We suggest that VEGF enters the
      systemic circulation and acts on microvessels to mediate hyperpermeability.
      OBJECTIVES: To quantify renal microvascular permeability and circulating VEGF
      concentration in severe psoriasis, and to investigate the relationship between
      plasma VEGF concentration and skin and joint involvement. DESIGN: Inception
      cohort studies of patients with generalized pustular psoriasis and plaque
      psoriasis. SETTING: St John's Institute of Dermatology, London, England.
      PATIENTS: Twenty-two patients (15 men and 7 women) with moderate and severe
      psoriasis were recruited (age range, 29-77 years; mean age, 47 years); 5 had
      generalized pustular psoriasis, 2 had erythrodermic psoriasis, and 15 had
      moderate-severe plaque psoriasis. An age- and sex-matched control group of 17
      individuals (10 men and 7 women) was recruited (age range, 29-69 years; mean age,
      42 years). RESULTS: There was pathological proteinuria in patients with relapsing
      generalized pustular psoriasis, (4-fold increase in urinary protein excretion
      rate in relapse compared with remission). In patients with moderate and severe
      psoriasis, mean plasma VEGF concentration during relapse was approximately 2.5
      times greater than during remission (mean VEGF(relapse) = 257 pg/mL; mean
      VEGF(remission) = 103 pg/mL; P<.01). There was a correlation between extent of
      skin involvement and plasma VEGF level (mean VEGF(severe psoriasis) = 365 pg/mL;
      mean VEGF(moderate psoriasis) = 149 pg/mL; P =.03). There was a correlation
      between presence of psoriatic arthritis and plasma VEGF level (mean relapse
      VEGF(arthritis) = 277 pg/mL; mean relapse VEGF(nonarthritis) = 103.5 pg/mL; P
      =.03). CONCLUSIONS: Generalized pustular psoriasis is accompanied by pathological
      proteinuria and elevated plasma VEGF levels. Plasma VEGF concentration is
      significantly elevated in patients with extensive skin and joint involvement and
      may act on renal microvasculature to induce hyperpermeability.

PMID- 12056963
TI  - Scalpdex: a quality-of-life instrument for scalp dermatitis.
AB  - OBJECTIVE: To develop a scalp dermatitis-specific quality-of-life instrument.
      METHODS: Based on the results of directed focus sessions with 8 patients with
      scalp psoriasis or seborrheic dermatitis, we conceptualized 3 major constructs
      that explain the way scalp dermatoses affect patient quality of life: symptoms,
      functioning, and emotions. We constructed a 23-item instrument, Scalpdex, and
      tested its reliability, responsiveness, and validity. RESULTS: Fifty-two
      dermatology patients completed the study. We demonstrated construct validity by
      confirming that the factors derived by principal axes factor analyses with
      orthogonal rotation correlated to our hypothesized scales (r = 0.76-0.84) and
      that differences in symptom, functioning, and emotion scores differed among the
      varying levels of self-reported scalp severity more than would be expected by
      chance (P<.05 by analysis of variance). The instrument demonstrated reliability
      with internal consistency (Cronbach alpha, 0.62-0.80) and reproducibility
      (intraclass correlation coefficient, 0.90-0.97). The quality-of-life scores
      changed in the expected direction in our test for responsiveness (P<or=.05, by
      paired t test for functioning and emotion for those who improved). We ascertained
      the discriminant capability of Scalpdex compared with a dermatological generic
      quality-of-life tool, Skindex, by demonstrating superior responsiveness
      (P<or=.005 by paired t test in functioning and emotion) and improved overall
      sensitivity in individual items. CONCLUSIONS: Scalpdex is, to our knowledge, the
      first quality-of-life instrument specifically for patients with scalp dermatitis
      that is reliable, valid, and responsive. Clinicians can use the instrument to
      determine which aspect of the disease most bothers the patient and to evaluate
      quality of life as one variable of responsiveness to the therapeutic
      intervention.

PMID- 12056962
TI  - Hypopigmentation associated with an adenovirus-mediated gp100/MART-1-transduced
      dendritic cell vaccine for metastatic melanoma.
AB  - BACKGROUND: Reports of vitiligo associated with metastases and rare cases of
      spontaneous regression of disease have fueled enthusiasm for immunologic
      approaches to the treatment of advanced melanoma. More recent strategies have
      focused on using antigen-presenting dendritic cells as vaccines. OBSERVATIONS: We
      observed 3 cases of leukoderma associated with a novel adenovirus-mediated
      gp100/MART-1-transduced dendritic cell (MART indicates melanoma antigen
      recognized by T cells). All 3 patients had advanced metastatic melanoma. Despite
      the development of this leukodermic response, all patients experienced disease
      progression while under treatment. CONCLUSION: We provide the initial evidence
      for effective induction of a leukodermic response with a gp100/MART-1-transduced
      dendritic cell vaccine.

PMID- 12056965
TI  - The financial impact on families of children with atopic dermatitis.

PMID- 12056964
TI  - Oral treatments for toenail onychomycosis: a systematic review.
AB  - OBJECTIVE: To identify and synthesize the evidence for the efficacy of oral
      treatments for fungal infections of the toenails. DESIGN: Systematic review of
      randomized controlled trials. INTERVENTIONS: Oral treatments for dermatophyte
      infections of the toenails. MAIN OUTCOME MEASURES: Cure confirmed by microscopy
      and culture results in patients with clinically diagnosed fungal infections. Data
      relating to the clinical cure rates were also extracted from the trials. RESULTS:
      A pooled analysis of 2 trials comparing mycological cure rates from continuous
      treatment with terbinafine (250 mg/d for 12 weeks) and continuous treatment with
      itraconazole (200 mg/d for 12 weeks) found a statistically significant difference
      in 11- and 12-month outcomes in favor of terbinafine (risk difference, -0.23 [95%
      confidence interval, -0.32 to -0.15]; number needed to treat, 5 [95% confidence
      interval, 4 to 8]). An analysis of clinical cure rates was not possible because
      of the diversity of definitions used in researching the effectiveness of oral
      antifungal drugs for onychomycosis. Only 3 trials gave a clear definition of
      clinical cure and presented data for these outcomes. CONCLUSIONS: There is good
      evidence that a continuous regimen of terbinafine (250 mg/d) for 3 months is the
      most effective oral treatment for fungally infected toenails. Consensus among
      researchers evaluating oral antifungal drugs for onychomycosis is needed to
      establish meaningful definitions of clinical cure. Most trials were funded by the
      pharmaceutical industry; we found little independent research, and this may have
      introduced bias to the review.

PMID- 12056966
TI  - Cyclooxygenase inhibitors for skin cancer prevention: are they beneficial enough?

PMID- 12056967
TI  - Immunosuppression and skin cancer: pathogenetic insights, therapeutic challenges,
      and opportunities for innovation.

PMID- 12056968
TI  - Reviewing the medical literature: statistics alone are not enough.

PMID- 12056969
TI  - Enlarging red plaque on the nose of an elderly woman.

PMID- 12056970
TI  - Lower extremity purpura.

PMID- 12056971
TI  - Generalized bullae in an infant.

PMID- 12056972
TI  - Tight skin and dysmorphic features in a newborn.

PMID- 12056973
TI  - Rice dream nondairy beverages.

PMID- 12056974
TI  - Segmental lesions are not always agminated.

PMID- 12056975
TI  - The teaspoon rule of applying sunscreen.

PMID- 12056976
TI  - Absence of Lisch nodules in sporadic neurofibromatosis type 1 may reflect somatic
      mosaicism.

PMID- 12056978
TI  - Severe influenzalike symptoms associated with methoxsalen photochemotherapy.

PMID- 12056980
TI  - Oral involvement in chronic graft-vs-host disease following allogenic bone marrow
      transplantation.

PMID- 12056979
TI  - Livedoid vasculitis with ulcerations: the role of antithrombin III deficiency and
      its therapeutic consequences.

PMID- 12056981
TI  - Clinical and in vitro responses of bilayered skin construct (graftskin) to
      meshing.

PMID- 12056987
TI  - Chronic fatigue syndrome. Clinical practice guidelines--2002.

PMID- 12056989
TI  - Surgery for epilepsy.

PMID- 12056988
TI  - Communication in the emergency department: separating the signal from the noise.

PMID- 12056990
TI  - Autism, autistic spectrum and the need for better definition.

PMID- 12056991
TI  - Maternal deaths in Australia.

PMID- 12056992
TI  - Communication loads on clinical staff in the emergency department.
AB  - OBJECTIVE: To measure communication loads on clinical staff in an acute clinical
      setting, and to describe the pattern of informal and formal communication events,
      Australia. DESIGN: Observational study. SETTING: Two emergency departments, one
      rural and one urban, in New South Wales hospitals, between June and July 1999.
      PARTICIPANTS: Twelve clinical staff members, comprising six nurses and six
      doctors. MAIN OUTCOME MEASURES: Time involved in communication; number of
      communication events, interruptions, and overlapping communications; choice of
      communication channel; purpose of communication. RESULTS: 35 hours and 13 minutes
      were observed, and 1286 distinct communication events were identified,
      representing 36.5 events per person per hour (95% CI, 34.5-38.5). A third of
      communication events (30.6%) were classified as interruptions, giving a rate of
      11.15 interruptions per hour for all subjects; 10% of communication time involved
      two or more concurrent conversations; and 12.7% of all events involved formal
      information sources such as patients' medical records. Face-to-face conversation
      accounted for 82%. While medical staff asked for information slightly less
      frequently than nursing staff (25.4% v 30.9%), they received information much
      less frequently (6.6% v 16.2%). CONCLUSION: Our results support the need for
      communication training in emergency departments and other similar workplaces. The
      combination of interruptions and multiple concurrent tasks may produce clinical
      errors by disrupting memory processes. About 90% of the information transactions
      observed involved interpersonal exchanges rather than interaction with formal
      information sources. This may put a low upper limit on the potential for
      improving information processes by introducing electronic medical records.

PMID- 12056993
TI  - Limitations of Health Insurance Commission (HIC) data for deriving prescribing
      indicators.
AB  - OBJECTIVES: To derive indicators of quality prescribing by Australian general
      practitioners based on Health Insurance Commission (HIC) data and assess the
      influence of incomplete capture of data on under-copayment drugs on the validity
      of these indicators. DESIGN: Two expert groups proposed prescribing indicators
      that can be derived from aggregate prescribing data, and which reflect important
      clinical or cost-effectiveness issues. Indicators were examined using HIC data
      and compared with national prescribing trends over time using Australian
      Statistics on Medicines. The effect of incomplete data capture on indicator
      interpretation was examined by stratifying GPs into five strata based on the
      proportion of concession card holders in their practice. PARTICIPANTS:
      Approximately 14,000 Australian GPs providing > or = 1500 Medicare services per
      year. MAIN OUTCOME MEASURES: Measures of prescribing for individual GPs (based on
      HIC data 1993-1997). RESULTS: Forty-three potentially useful indicators were
      identified. These covered a fairly narrow range of prescribing activities and
      many required additional clinical information for interpretation. Indicators
      based on prescribing rates gave a misleading picture of prescribing trends where
      the extent of HIC data capture changed over time. Indicators expressed as ratios
      that reflected choice of agent within a drug class were less affected by
      incomplete data capture. CONCLUSIONS: Indicators of quality prescribing can be
      derived from HIC data. However, indicators for under-copayment drugs that
      represent prescribing rates may unfairly classify doctors practising in areas of
      socioeconomic disadvantage or high morbidity as "high prescribers". Ratio
      indicators are more robust, and may be more valid prescribing measures. If HIC
      data are to be used to monitor the quality of prescribing, data on all
      prescriptions dispensed will be needed.

PMID- 12056994
TI  - Projections of Australian obstetricians ceasing practice and the reasons.
AB  - OBJECTIVES: To assess the intentions of Australia's specialist obstetricians to
      cease practice and their reasons for abandoning this specialty. DESIGN: A
      structured questionnaire posted to Fellows of the Royal Australian and New
      Zealand College of Obstetricians and Gynaecologists (RANZCOG), issued 11 July
      2001 with a return date of 31 July 2001 (in practice, responses were accepted up
      to 31 August 2001). PARTICIPANTS: Australian specialists holding a Fellowship of
      the RANZCOG. MAIN OUTCOME MEASURES: Demographic data (eg, age, sex); type and
      location of practice; past, current and intended future obstetric practice;
      reasons for stopping practice; cost of indemnity premiums; experience of
      litigation and its influence on practice; and experience in giving medicolegal
      opinion. RESULTS: The response rate was 74% (829/1116), with 826 responses
      fulfilling our selection criteria. The median number of years since admission as
      a Fellow was 17 (range, 1-47 years), and 19% (158/817) of respondents were women
      (9 people did not specify their sex). Of the 826 respondents, 596 (72%) were
      currently practising obstetrics, 548 (66%) intended to still be practising after
      one year, 365 (44%) intended to be practising after five years, and 196 (24%)
      intended to be practising after 10 years. The median indemnity premium in 2001-02
      was $35,515 (range, nil to $156,000) for practising obstetricians. The main
      reasons given for ceasing obstetrics were intention to specialise in gynaecology,
      fear of litigation, high indemnity costs, family disruption, and long working
      hours. About two-thirds of respondents (557/818) had experienced the threat of
      litigation, and almost all (768/803) desired some type of "no-fault" indemnity
      scheme. Thirty-three of the 314 respondents who had given medicolegal opinions
      accounted for 71% of the total number of opinions. Many of these were non
      practising obstetricians who were not accredited RANZCOG expert witnesses.
      CONCLUSION: There will soon be a shortage of experienced practising obstetricians
      in Australia.

PMID- 12056995
TI  - Ventricular tachycardia following ingestion of a commonly used antihistamine.
AB  - This report describes ventricular tachycardia, likely to have been torsade de
      pointes, following ingestion of the non-sedating antihistamine loratadine.
      Documentation of the arrhythmia was made possible by the automatic electrogram
      storage facility of an implanted defibrillator in a patient with no prior history
      of cardiac arrhythmia.

PMID- 12056996
TI  - Biological agents as weapons 1: smallpox and botulism.
AB  - 1. Early recognition by clinicians of illnesses suggesting a biological attack is
      integral to the public health response. 2. The four biological agents of most
      concern are smallpox virus, botulinum toxin, and anthrax and plague bacteria. 3.
      Smallpox is distinguishable from chickenpox by the prominent prodromal period and
      lesions that develop at the same pace and, on any part of the body, appear
      identical to each other, evolve slowly and are peripherally distributed. 4. The
      degree of protection conferred by smallpox vaccination given 20 or more years ago
      is unknown. 5. Foodborne and inhalational botulism could result from deliberate
      release of toxin. 6. Botulism presents with cranial nerve palsies and descending
      paralysis in a patient with normal conscious state and no fever.

PMID- 12056997
TI  - Appetising solutions: an edible vaccine for measles.
AB  - The cultivation of plants with specific properties has been the foundation of
      medicine for milennia. Modern biotechnology may one day extend their medicinal
      uses to include the delivery of vaccines. Edible vaccines that are heat stable,
      easy to administer and cheap to produce have the potential to redress many of the
      production, distribution and delivery limitations faced by traditional vaccines.
      Published data have shown that the concept of an edible vaccine is valid.
      Transition from a model system into a practical reality still has some way to go,
      including managing issues of oral tolerance, genetically modified organism
      safety, and effective vaccine doses. Successful edible vaccines have the
      potential to transform health policy and practice in both developed and
      developing countries.

PMID- 12056998
TI  - Spinal surgery and severe vitamin D deficiency.

PMID- 12056999
TI  - 5: Hospital-in-the-home treatment of infectious diseases.
AB  - 1. A growing range of infections can be safely and effectively treated with
      parenteral antimicrobial therapy at home, including cellulitis, pyelonephritis,
      pneumonia, endocarditis, osteomyelitis, septic arthritis and deep abscesses. 2.
      Patients may be admitted to HITH directly from the emergency department or after
      a period of in-hospital care; they must be thoroughly assessed for suitability,
      including clinical stability and social circumstances, and both patient and carer
      consent must be obtained. 3. Patients should be medically reviewed weekly at the
      hospital to monitor progress of therapy and check for possible complications,
      including adverse drug reactions. 4. Antibiotic selection should be based on
      appropriate prescribing principles rather than purely dosing convenience. 5.
      Innovative dosing regimens, including once-daily aminoglycosides, continuous
      infusion beta-lactams (eg, flucloxacillin), once- or twice-daily cephalosporins
      (eg, cephazolin) and oral fluoroquinolones (eg, ciprofloxacin) provide effective
      therapy for a wide range of infections that would have previously required in
      hospital care. 6. Appropriate use of HITH leads to improved patient and carer
      satisfaction, efficient in-hospital bed use and possibly some financial
      efficiencies. Not all patients receiving intravenous antibiotics need to be in
      hospital

PMID- 12057000
TI  - Sharp v Port Kembla RSL Club: establishing causation of laryngeal cancer by
      environmental tobacco smoke.

PMID- 12057001
TI  - Gonorrhoea screening in general practice: perceived barriers and strategies to
      improve screening rates.

PMID- 12057003
TI  - Assessing children's fitness for scuba diving.

PMID- 12057002
TI  - Separating politics and scientific research on heroin prescription.

PMID- 12057004
TI  - Death in Antarctica.

PMID- 12057005
TI  - Books as carriers of disease.

PMID- 12057006
TI  - Overexpression and functional characterization of an ABC (ATP-binding cassette)
      transporter encoded by the genes drrA and drrB of Mycobacterium tuberculosis.
AB  - The genes encoding ATP-binding cassette (ABC) transporters occupy 2.5% of the
      genome of Mycobacterium tuberculosis. However, none of these putative ABC
      transporters has been characterized so far. We describe the development of
      expression systems for simultaneous expression of the ATP-binding protein DrrA
      and the membrane integral protein DrrB which together behave as a functional
      doxorubicin efflux pump. Doxorubicin uptake in Escherichia coli or Mycobacterium
      smegmatis expressing DrrAB was inhibited by reserpine, an inhibitor of ABC
      transporters. The localization of DrrA to the membrane depended on the
      simultaneous expression of DrrB. ATP binding was positively regulated by
      doxorubicin and daunorubicin. At the same time, DrrB appeared to be sensitive to
      proteolysis when expressed alone in the absence of DrrA. Simultaneous expression
      of the two polypeptides was essential to obtain a functional doxorubicin efflux
      pump. Expression of DrrAB in E. coli conferred 8-fold increased resistance to
      ethidium bromide, a cationic compound. 2',7'-bis-(2-Carboxyethyl)-5(6)
      carboxyfluorescein (BCECF), a neutral compound, also behaved as a substrate of
      the reconstituted efflux pump. When expressed in M. smegmatis, DrrAB conferred
      resistance to a number of clinically relevant, structurally unrelated
      antibiotics. The resistant phenotype could be reversed by verapamil and
      reserpine, two potent inhibitors of ABC transporters.

PMID- 12057008
TI  - P2X7 receptors activate protein kinase D and p42/p44 mitogen-activated protein
      kinase (MAPK) downstream of protein kinase C.
AB  - Protein kinase D (PKD), also called protein kinase Cmu (PKCmu), is a
      serine/threonine kinase that has unique enzymic and structural properties
      distinct from members of the PKC family of proteins. In freshly isolated rat
      parotid acinar salivary cells, extracellular ATP rapidly increased the activity
      and phosphorylation of PKD. The stimulation by ATP required high concentrations,
      was mimicked by the P2X(7) receptor ligand BzATP [2'- and 3'-O-(4
      benzoylbenzoyl)ATP], and was blocked by Mg(2+) and 4,4'-di-isothiocyano-2,2'
      stilbene disulphonate (DIDS), suggesting that activation of PKD was mediated by
      P2X(7) receptors, which are ligand-gated non-selective cation channels. Phorbol
      ester (PMA) and the activation of muscarinic and substance P receptors also
      increased PKD activity. PKC inhibitors blocked ligand-dependent PKD activation
      and phosphorylation, determined by in vitro phosphorylation studies and by
      phospho-specific antibodies to two activation loop sites (Ser(744) and Ser(748))
      and an autophosphorylation site (Ser(916)). ATP and BzATP also increased the
      tyrosine phosphorylation and activity of PKCdelta, and these stimuli also
      increased extracellular signal-regulated protein kinase (ERK) 1/2 activity in a
      PKC-dependent manner. PKD activation was not promoted by pervanadate (an
      inhibitor of tyrosine phosphatases) and was not blocked by PP1 (an inhibitor of
      Src family kinases) or genistein (a tyrosine kinase inhibitor), suggesting that
      tyrosine kinases and phosphatases did not play a major role in PKD activation.
      P2X(7) receptor-mediated signalling events were not dependent on Ca(2+) entry.
      These studies indicate that PKC is involved in cellular signalling initiated by
      P2X(7) receptors as well as by G-protein-coupled receptors, and demonstrate that
      PKD and ERK1/2 are activated in similar PKC-dependent signalling pathways
      initiated by these diverse receptor types.

PMID- 12057009
TI  - Quantitative analysis of DNA levels in maternal plasma in normal and Down
      syndrome pregnancies.
AB  - BACKGROUND: We investigated fetal and total DNA levels in maternal plasma in
      patients bearing fetuses affected with Down syndrome in comparison to controls
      carrying fetuses with normal karyotype. METHODS: DNA levels in maternal plasma
      were measured using real-time quantitative PCR using SRY and beta-globin genes as
      markers. Twenty-one pregnant women with a singleton fetus at a gestational age
      ranging from 15 to 19 weeks recruited before amniocentesis (carried out for
      reasons including material serum screening and advanced material age), and 16
      pregnant women bearing fetuses affected with Down syndrome between 17 to 22 weeks
      of gestation were involved in the study. RESULTS: The specificity of the system
      reaches 100% (no Y signal was detected in 14 women pregnant with female fetuses)
      and the sensitivity 91.7% (SRY amplification in 22 of 24 examined samples). The
      median fetal DNA levels in women carrying Down syndrome (n=11) and the controls
      (n=13) were 23.3 (range 0-58.5) genome-equivalents/ml and 24.5 (range 0-47.5)
      genome-equivalents/ml of maternal plasma, respectively (P = 0.62). The total
      median DNA levels in pregnancies with Down syndrome and the controls were 10165
      (range 615-65000) genome-equivalents/ml and 7330 (range 1300-36750) genome
      equivalents/ml, respectively (P = 0.32). The fetal DNA proportion in maternal
      plasma was 0%-6 % (mean 0.8%) in women carrying Down syndrome and 0%-2.6 % (mean
      0.7 %) in the controls, respectively (P=0.86). CONCLUSIONS: Our study revealed no
      difference in fetal DNA levels and fetal DNA: maternal DNA ratio between the
      patients carrying Down syndrome fetuses and the controls.

PMID- 12057007
TI  - Signal transducers and activators of transcription 3 (STAT3) inhibits
      transcription of the inducible nitric oxide synthase gene by interacting with
      nuclear factor kappaB.
AB  - Prolific generation of NO by inducible nitric oxide synthase (iNOS) can cause
      unintended injury to host cells during glomerulonephritis and other inflammatory
      diseases. While much is known about the mechanisms of iNOS induction, few
      transcriptional repressors have been found. We explored the role of signal
      transducers and activators of transcription 3 (STAT3) proteins in interleukin
      (IL)-1beta- and lipopolysaccharide (LPS)+interferon (IFN)-gamma-mediated iNOS
      induction in murine mesangial cells. Both stimuli induced rapid phosphorylation
      of STAT3 and sequence-specific STAT3 DNA-binding activity. Supershift assays with
      a STAT3 element probe demonstrated that nuclear factor kappaB (NF-kappaB) p65 and
      p50 complexed with STAT3 in the DNA-protein complex. The direct interaction of
      STAT3 and NF-kappaB p65 was verified in vivo by co-immunoprecipitation and in
      vitro by pull-down assays with glutathione S-transferase-NF-kappaB p65 fusion
      protein and in vitro -translated STAT3alpha. Overexpression of STAT3 dramatically
      inhibited IL-1beta- or LPS+IFN-gamma-mediated induction of iNOS promoter
      luciferase constructs that contained the wild-type iNOS promoter or ones
      harbouring mutated STAT-binding elements. In tests of indirect inhibitory effects
      of STAT3, overexpression of STAT3 dramatically inhibited the activity of an NF
      kappaB-dependent promoter devoid of STAT-binding elements without affecting NF
      kappaB DNA-binding activity. Thus STAT3, via direct interactions with NF-kappaB
      p65, serves as a dominant-negative inhibitor of NF-kappaB activity to suppress
      indirectly cytokine induction of the iNOS promoter in mesangial cells. These
      results provide a new model for the termination of NO production by activated
      iNOS following exposure to pro-inflammatory stimuli.

PMID- 12057010
TI  - Acute bilateral emphysematous pyelonephritis successfully managed by medical
      therapy alone: a case report and review of the literature.
AB  - BACKGROUND: Bilateral emphysematous pyelonephritis is a life threatening
      condition usually occurring in diabetics. Management of this condition has
      traditionally been aggressive and surgery is considered mandatory. However, this
      is itself a hazardous intervention in a septic, unstable patient with circulatory
      or liver failure. When bilateral disease is present, the need for long-term
      dialysis is obviously unavoidable. CASE PRESENTATION: We herein report one of the
      few cases of bilateral emphysematous pyelonephritis successfully managed by non
      surgical treatment.

PMID- 12057011
TI  - Bacterial cholangitis causing secondary sclerosing cholangitis: a case report.
AB  - BACKGROUND: Although bacterial cholangitis is frequently mentioned as a cause of
      secondary sclerosing cholangitis, it appears to be extremely rare, with only one
      documented case ever reported. CASE PRESENTATION: A 48-year-old woman presented
      with an episode of acute biliary pancreatitis that was complicated by pancreatic
      abcess formation. After 3 months she had an episode of severe pyogenic (E. Coli)
      cholangitis that recurred over the subsequent 7 months on a further two
      occasions. Initially, cholangiography suggested the presence of extra-biliary
      intrahepatic abcesses while repeated investigations demonstrated development of
      multiple segmental biliary duct strictures. After maintenance antibiotic
      treatment was started, no episodes of cholangitis occurred over a 14-month
      period. CONCLUSIONS: Sclerosing cholangitis can rapidly develop after an episode
      of bacterial cholangitis. Extra-biliary involvement of the hepatic parenchyma
      with abcess formation may be a risk factor for developing this rare but
      particularly severe complication.

PMID- 12057012
TI  - Accumulation of dehydrin-like proteins in the mitochondria of cereals in response
      to cold, freezing, drought and ABA treatment.
AB  - BACKGROUND: Dehydrins are known as Group II late embryogenesis abundant proteins.
      Their high hydrophilicity and thermostability suggest that they may be structure
      stabilizers with detergent and chaperone-like properties. They are localised in
      the nucleus, cytoplasm, and plasma membrane. We have recently found putative
      dehydrins in the mitochondria of some cereals in response to cold. It is not
      known whether dehydrin-like proteins accumulate in plant mitochondria in response
      to stimuli other than cold stress. RESULTS: We have found five putative dehydrins
      in the mitochondria of winter wheat, rye and maize seedlings. Two of these
      polypeptides had the same molecular masses in all three species (63 and 52 kD)
      and were thermostable. Drought, freezing, cold, and exogenous ABA treatment led
      to higher accumulation of dehydrin-like protein (dlp) 63 kD in the rye and wheat
      mitochondria. Protein 52 kD was induced by cold adaptation and ABA. Some
      accumulation of these proteins in the maize mitochondria was found after cold
      exposition only. The other three proteins appeared to be heat-sensitive and were
      either slightly induced or not induced at all by all treatments used.
      CONCLUSIONS: We have found that, not only cold, but also drought, freezing and
      exogenous ABA treatment result in accumulation of the thermostable dehydrins in
      plant mitochondria. Most cryotolerant species such as wheat and rye accumulate
      more heat-stable dehydrins than cryosensitive species such as maize. It has been
      supposed that their function is to stabilize proteins in the membrane or in the
      matrix. Heat-sensitive putative dehydrins probably are not involved in the stress
      reaction and adaptation of plants.

PMID- 12057013
TI  - Complex splicing pattern generates great diversity in human NF1 transcripts.
AB  - BACKGROUND: Mutation analysis of the neurofibromatosis type 1 (NF1) gene has
      shown that about 30% of NF1 patients carry a splice mutation resulting in the
      production of one or several shortened transcripts. Some of these transcripts
      were also found in fresh lymphocytes of healthy individuals, albeit typically at
      a very low level. Starting from this initial observation, we were interested to
      gain further insight into the complex nature of NF1 mRNA processing. RESULTS: We
      have used a RT-PCR plasmid library based method to identify novel NF1 splice
      variants. Several transcripts were observed with specific insertions/deletions
      and a survey was made. This large group of variants detected in one single gene
      allows to perform a comparative analysis of the factors involved in splice
      regulation. Exons that are prone to skipping were systematically analysed for 5'
      and 3' splice site strength, branch point strength and secondary structure.
      CONCLUSION: Our study revealed a complex splicing pattern, generating a great
      diversity in NF1 transcripts. We found that, on average, exons that are spliced
      out in part of the mRNA have significantly weaker acceptor sites. Some variants
      identified in this study could have distinct roles and might expand our knowledge
      of neurofibromin.

PMID- 12057014
TI  - The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound
      fibroblasts, accelerating development of granulation tissue.
AB  - BACKGROUND: During wound repair, fibroblasts orchestrate replacement of the
      provisional matrix formed during clotting with tenascin, cellular fibronectin and
      collagen III. These, in turn, are critical for migration of endothelial cells,
      keratinocytes and additional fibroblasts into the wound site. Fibroblasts are
      also important in the deposition of collagen I during scar formation. The CXC
      chemokine chicken Chemotactic and Angiogenic Factor (cCAF), is highly expressed
      by fibroblasts after wounding and during development of the granulation tissue,
      especially in areas where extracellular matrix (ECM) is abundant. We hypothesized
      that cCAF stimulates fibroblasts to produce these matrix molecules. RESULTS: Here
      we show that this chemokine can stimulate precocious deposition of tenascin,
      fibronectin and collagen I, but not collagen III. Studies in culture and in vivo
      show that tenascin stimulation can also be achieved by the N-terminal 15 aas of
      the protein and occurs at the level of gene expression. In contrast, stimulation
      of fibronectin and collagen I both require the entire molecule and do not involve
      changes in gene expression. Fibronectin accumulation appears to be linked to
      tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF
      is chemotactic for fibroblasts and accelerates their migration. CONCLUSIONS:
      These previously unknown functions for chemokines suggest that cCAF, the chicken
      orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts
      into the wound site and stimulating them to produce ECM molecules, leading to
      precocious development of granulation tissue. This acceleration of the repair
      process may have important application to healing of impaired wounds.

PMID- 12057016
TI  - Preparation of pure and intact Plasmodium falciparum plasma membrane vesicles and
      partial characterisation of the plasma membrane ATPase.
AB  - BACKGROUND: In host erythrocytes, the malaria parasite must contend with ion and
      drug transport across three membranes; its own plasma membrane, the
      parasitophorous membrane and the host plasma membrane. Isolation of pure and
      intact Plasmodium falciparum plasma membrane would provide a suitable model to
      elucidate the possible role played by the parasite plasma membrane in ion balance
      and drug transport. RESULTS: This study describes a procedure for isolating
      parasite plasma membrane from P. falciparum-infected erythrocytes. With this
      method, the trophozoites released by saponin treatment were cleansed of
      erythrocyte membranes using anti-erythrocyte antibodies fixed to polystyrene
      beads. These trophozoites were then biotinylated and the parasite plasma membrane
      was disrupted by nitrogen cavitation. This process allows the membranes to reform
      into vesicles. The magnetic streptavidin beads bind specifically to the
      biotinylated parasite plasma membrane vesicles facilitating their recovery with a
      magnet. These vesicles can then be easily released from the magnetic beads by
      treatment with dithiotreithol. The parasite plasma membrane showed optimal ATPase
      activity at 2 mM ATP and 2 mM Mg2+. It was also found that Ca2+ could not
      substitute for Mg2+ ATPase activity in parasite plasma membranes whereas activity
      was completely preserved when Mn2+ was used instead of Mg2+. Other nucleoside
      triphosphates tested were hydrolysed as efficiently as ATP, while the nucleoside
      monophosphate AMP was not. CONCLUSIONS: We have described the successful
      isolation of intact P. falciparum plasma membrane vesicles free of contaminating
      organelles and determined the experimental conditions for optimum ATPase
      activity.

PMID- 12057015
TI  - Characterization of subcellular localization and stability of a splice variant of
      G alpha i2.
AB  - BACKGROUND: Alternative mRNA splicing of alpha(i2), a heterotrimeric G protein
      alpha subunit, has been shown to produce an additional protein, termed
      salpha(i2). In the salpha(i2) splice variant, 35 novel amino acids replace the
      normal C-terminal 24 amino acids of alpha(i2). Whereas alpha(i2) is found
      predominantly at cellular plasma membranes, salpha(i2) has been localized to
      intracellular Golgi membranes, and the unique 35 amino acids of salpha(i2) have
      been suggested to constitute a specific targeting signal. RESULTS: This paper
      proposes and examines an alternative hypothesis: disruption of the normal C
      terminus of alpha(i2) produces an unstable protein that fails to localize to
      plasma membranes. salpha(i2) is poorly expressed upon transfection of cultured
      cells; however, radiolabeling indicated that alpha(i2) and salpha(i2) undergo
      myristoylation, a co-translational modification, equally well suggesting that
      protein stability rather than translation is affected. Indeed, pulse-chase
      analysis indicates that salpha(i2) is more rapidly degraded compared to
      alpha(i2). Co-expression of betagamma rescues PM localization and increases
      expression of salpha(i2). In addition, alpha(i2)A327S, a mutant previously shown
      to be unstable and defective in guanine-nucleotide binding, and alpha(i2)(1-331),
      in which the C-terminal 24 amino acids of alpha(i2) are deleted, show a similar
      pattern of subcellular localization as salpha(i2) (i.e., intracellular membranes
      rather than plasma membranes). Finally, salpha(i2) displays a propensity to
      localize to potential aggresome-like structures. CONCLUSIONS: Thus, instead of
      the novel C-terminus of salpha(i2) functioning as a specific Golgi targeting
      signal, the results presented here indicate that the disruption of the normal C
      terminus of alpha(i2) causes mislocalization and rapid degradation of salpha(i2).

PMID- 12057018
TI  - A possible alternative method for collecting mosquito larvae in rice fields.
AB  - BACKGROUND: Rice fields are efficient breeding places for malaria vectors in
      Madagascar. In order to establish as easily as possible if a rice field is an
      effective larval site for anophelines, we compared classical dipping versus a net
      as methods of collecting larvae. RESULTS: Using similar collecting procedures, we
      found that the total number of anopheline larvae collected with the net was
      exactly double (174/87) that collected by dipping. The number of anopheline
      species collected was also greater with a net. CONCLUSIONS: The net is an
      effective means of collecting anopheline larvae and can be used for qualitative
      ecological studies and to rapidly determine which rice fields are containing
      malaria vectors.

PMID- 12057017
TI  - Characterisation and expression of a PP1 serine/threonine protein phosphatase
      (PfPP1) from the malaria parasite, Plasmodium falciparum: demonstration of its
      essential role using RNA interference.
AB  - BACKGROUND: Reversible protein phosphorylation is relatively unexplored in the
      intracellular protozoa of the Apicomplexa family that includes the genus
      Plasmodium, to which belong the causative agents of malaria. Members of the PP1
      family represent the most highly conserved protein phosphatase sequences in
      phylogeny and play essential regulatory roles in various cellular pathways.
      Previous evidence suggested a PP1-like activity in Plasmodium falciparum, not yet
      identified at the molecular level. RESULTS: We have identified a PP1 catalytic
      subunit from P. falciparum and named it PfPP1. The predicted primary structure of
      the 304-amino acid long protein was highly similar to PP1 sequences of other
      species, and showed conservation of all the signature motifs. The purified
      recombinant protein exhibited potent phosphatase activity in vitro. Its
      sensitivity to specific phosphatase inhibitors was characteristic of the PP1
      class. The authenticity of the PfPP1 cDNA was further confirmed by mutational
      analysis of strategic amino acid residues important in catalysis. The protein was
      expressed in all erythrocytic stages of the parasite. Abrogation of PP1
      expression by synthetic short interfering RNA (siRNA) led to inhibition of
      parasite DNA synthesis. CONCLUSIONS: The high sequence similarity of PfPP1 with
      other PP1 members suggests conservation of function. Phenotypic gene knockdown
      studies using siRNA confirmed its essential role in the parasite. Detailed
      studies of PfPP1 and its regulation may unravel the role of reversible protein
      phosphorylation in the signalling pathways of the parasite, including glucose
      metabolism and parasitic cell division. The use of siRNA could be an important
      tool in the functional analysis of Apicomplexan genes.

PMID- 12057019
TI  - A theoretical approach to predicting the success of genetic manipulation of
      malaria mosquitoes in malaria control.
AB  - BACKGROUND: Mosquitoes that have been genetically modified to better encapsulate
      the malaria parasite Plasmodium falciparum are being considered as a possible
      tool in the control of malaria. Hopes for this have been raised with the
      identification of genes involved in the encapsulation response and with advances
      in the tools required to transform mosquitoes. However, we have only very little
      understanding of the conditions that would allow such genes to spread in natural
      populations. METHODS: We present here a theoretical model that combines
      population genetical and epidemiological processes, thereby allowing one to
      predict not only these conditions (intensity of transmission, evolutionary cost
      of resistance, tools used to drive the genes) but also the impact of the spread
      of refractoriness on the prevalence of the disease. RESULTS: The main conclusions
      are 1) that efficient transposons will generally be able to drive genes that
      confer refractoriness through populations even if there is a substantial
      (evolutionary) cost of refractoriness, but 2) that this will decrease malaria
      prevalence in the human population substantially only if refractoriness is close
      to 100% effective. CONCLUSIONS: If refractoriness is less than 100% effective
      (because of, for example, environmentally induced variation in the effectiveness
      of the mosquito's immune response), control programmes based on genetic
      manipulation of mosquitoes will have very little impact on the epidemiology of
      malaria, at least in areas with intense transmission.

PMID- 12057020
TI  - Detection of malaria parasites by nested PCR in south-eastern, Iran: evidence of
      highly mixed infections in Chahbahar district.
AB  - BACKGROUND: Rapid diagnosis and correct treatment of cases are the main
      objectives of control programs in malaria-endemic areas. METHODS AND RESULTS: To
      evaluate these criteria and in a comparative study, blood specimens were
      collected from 120 volunteers seeking care at the Malaria Health Center in
      Chahbahar district. One hundred and seven out of 120 Giemsa-stained slides were
      positive for malaria parasites by microscopy. Eighty-four (70%) and 20 (16.7%)
      were identified as having only Plasmodium vivax and Plasmodium falciparum
      infections, respectively, while only 3 (2.5%) were interpreted as having mixed P.
      vivax-P. falciparum infections. The target DNA sequence of the 18S small sub-unit
      ribosomal RNA (ssrRNA) gene was amplified by Polymerase Chain Reaction (PCR) and
      used for the diagnosis of malaria in south-eastern Iran. One hundred twenty blood
      samples were submitted and the results were compared to those of routine
      microscopy. The sensitivity of PCR for detection of P. vivax and P. falciparum
      malaria was higher than that of microscopy: nested PCR detected 31 more mixed
      infections than microscopy and parasite positive reactions in 9 out of the 13
      microscopically negative samples. The results also confirmed the presence of P.
      vivax and P. falciparum. CONCLUSIONS: These results suggest that, in places where
      transmission of both P. vivax and P. falciparum occurs, nested PCR detection of
      malaria parasites can be a very useful complement to microscopical diagnosis.

PMID- 12057022
TI  - Training practitioners in preparing systematic reviews: a cross-sectional survey
      of participants in the Australasian Cochrane Centre training program.
AB  - BACKGROUND: Although systematic reviews of health care interventions are an
      invaluable tool for health care providers and researchers, many potential authors
      never publish reviews. This study attempts to determine why some people with
      interest in performing systematic reviews do not subsequently publish a review;
      and what steps could possibly increase review completion. METHODS: Cross
      sectional survey by email and facsimile of the 179 participants in Australasian
      Cochrane Centre training events between 1998 and 2000. RESULTS: Ninety-two
      participants responded to the survey (51 percent). Response rate of deliverable
      surveys was 82 percent (92/112). The remainder of the participants had invalid or
      no contact information on file. More than 75 percent of respondents felt that the
      current workshops met their needs for training. The most critical barriers to
      completion of a Cochrane review were: lack of time (80 percent), lack of
      financial support (36 percent), methodological problems (23 percent) and problems
      with group dynamics (10 percent). CONCLUSIONS: Strategies to protect reviewer
      time and increase the efficiency of the review process may increase the numbers
      of trained reviewers completing a systematic review.

PMID- 12057021
TI  - Malarone treatment failure and in vitro confirmation of resistance of Plasmodium
      falciparum isolate from Lagos, Nigeria.
AB  - We report the first in vitro and genetic confirmation of Malarone
      (GlaxoSmithKline; atovaquone and proguanil hydrochloride) resistance in
      Plasmodium falciparum acquired in Africa. On presenting with malaria two weeks
      after returning from a 4-week visit to Lagos, Nigeria without prophylaxis, a male
      patient was given a standard 3-day treatment course of Malarone. Twenty-eight
      days later the parasitaemia recrudesced. Parasites were cultured from the blood
      and the isolate (NGATV01) was shown to be resistant to atovaquone and the
      antifolate pyrimethamine. The cytochrome b gene of isolate NGATV01 showed a
      single mutation, Tyr268Asn which has not been seen previously.

PMID- 12057023
TI  - Experimental arthritis induced by a clinical Mycoplasma fermentans isolate.
AB  - BACKGROUND: Mycoplasma fermentans has been associated with rheumatoid arthritis.
      Recently, it was detected in the joints and blood of patients with rheumatoid
      arthritis, but it is not clear yet how the bacteria enter the body and reach the
      joints. The purpose of this study was to determine the ability of M. fermentans
      to induce experimental arthritis in rabbits following inoculation of the bacteria
      in the trachea and knee joints. METHODS: P-140 and PG-18 strains were each
      injected in the knee joints of 14 rabbits in order to evaluate and compare their
      arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order
      to test the ability of the bacteria to reach the joints and induce arthritis.
      RESULTS: M. fermentans produced an acute arthritis in rabbits. Joint swelling
      appeared first in rabbits injected with P-140, which caused a more severe
      arthritis than PG-18. Both strains were able to migrate to the uninoculated knee
      joints and they were detected viable in the joints all along the duration of the
      experiment. Changes in the synovial tissue were more severe by the end of the
      experiment and characterized by the infiltration of neutrophils and substitution
      of adipose tissue by connective tissue. Rabbits intracheally injected with P-140
      showed induced arthritis and the bacteria could be isolated from lungs, blood,
      heart, kidney, spleen, brain and joints. CONCLUSION: M. fermentans induced
      arthritis regardless of the inoculation route. These findings may help explain
      why mycoplasmas are commonly isolated from the joints of rheumatic patients.

PMID- 12057024
TI  - Salivary testosterone levels in preadolescent children.
AB  - BACKGROUND: Saliva reflects the plasma free fraction of testosterone which is
      biologically active, and available for uptake by tissues. Testosterone
      concentration in saliva, though differing slightly from the concentration of
      unbound testosterone in serum, is in good correlation with the latter, indicating
      that salivary testosterone provides a reliable method for determination of serum
      free testosterone. The study aimed to investigate salivary testosterone levels
      and their changes in preadolescent children and to study sexual dimorphism.
      METHODS: Testosterone levels were determined in 203 healthy preadolescent
      children (77 girls and 126 boys) from saliva samples by radioimmunoassay.
      Sampling was performed once a year with respect to circadian and seasonal
      fluctuations of testosterone. Data were statistically analyzed by Statgraphic
      software. RESULTS: Mean salivary testosterone concentrations (+/- SD) were 0.038
      +/- 0.012 nmol/L and 0.046 +/- 0.026 nmol/L for girls and boys, with the medians
      0.035 nmol/L and 0.041 nmol/L, respectively. Statistical analysis did not prove
      changes in salivary testosterone concentrations in the preadolescent period of
      life, with an exception of the insignificant fall at the age of 7 years, and an
      insignificant rise at the age of 9 years in girls. CONCLUSIONS: Generally it can
      be concluded that salivary testosterone levels in our prepubertal subjects
      remained stable. There was no significant increase of salivary testosterone
      levels from the age of 6 until the age of 9 in both sexes. Sexual dimorphism in
      salivary testosterone levels was proved with significantly higher (p = 0.009)
      salivary testosterone levels in boys than in girls.

PMID- 12057026
TI  - Cellular responses to Plasmodium falciparum erythrocyte membrane protein-1: use
      of relatively conserved synthetic peptide pools to determine CD4 T cell responses
      in malaria-exposed individuals in Benin, West Africa.
AB  - BACKGROUND: Plasmodium falciparum erythrocyte membrane protein-1, a variant
      antigen of the malaria parasite, is potentially a target for the immune response.
      It would be important to determine whether there are CD4 T cells that recognise
      conserved regions. However, within the relatively conserved region, there is
      variation. It is not possible to test T cell responses from small field samples
      with all possible peptides. METHODS: We have aligned sequences that are
      relatively conserved between several PfEMP1 molecules, and chosen a
      representative sequence similar to most of the PfEMP1 variants. Using these
      peptides as pools representing CIDRalpha, CIDRbeta and DBLbeta-delta domains,
      DBLalpha domain, and EXON 2 domain of PfEMP1, we measured the CD4 T cell
      responses of malaria-exposed donors from Benin, West Africa by a FACS based
      assay. RESULTS: All the three peptide pools elicited a CD4 T cell response in a
      proportion of malaria-exposed and non-exposed donors. CD4 T cell proliferation
      occurs at a relatively higher magnitude to peptide pools from the DBLalpha and
      EXON 2 in the malaria-exposed donors living in Benin than in the UK malaria
      unexposed donors. CONCLUSIONS: These findings suggest that an immunological
      recall response to conserved peptides of a variant antigen can be measured.
      Further testing of individual peptides in a positive pool will allow us to
      determine those conserved sequences recognised by many individuals. These types
      of assays may provide information on conserved peptides of PfEMP1 which could be
      useful for stimulating T cells to provide help to P. falciparum specific B cells.

PMID- 12057025
TI  - Retroviral expression of a kinase-defective IGF-I receptor suppresses growth and
      causes apoptosis of CHO and U87 cells in-vivo.
AB  - BACKGROUND: Phosphatidylinositol-3,4,5-triphosphate (PtdInsP3) signaling is
      elevated in many tumors due to loss of the tumor suppressor PTEN, and leads to
      constitutive activation of Akt, a kinase involved in cell survival.
      Reintroduction of PTEN in cells suppresses transformation and tumorigenicity.
      While this approach works in-vitro, it may prove difficult to achieve in-vivo. In
      this study, we investigated whether inhibition of growth factor signaling would
      have the same effect as re-expression of PTEN. METHODS: Dominant negative IGF-I
      receptors were expressed in CHO and U87 cells by retroviral infection. Cell
      proliferation, transformation and tumor formation in athymic nude mice were
      assessed. RESULTS: Inhibition of IGF-IR signaling in a CHO cell model system by
      expression of a kinase-defective IGF-IR impairs proliferation, transformation and
      tumor growth. Reduction in tumor growth is associated with an increase in
      apoptosis in-vivo. The dominant-negative IGF-IRs also prevented growth of U87
      PTEN-negative glioblastoma cells when injected into nude mice. Injection of an
      IGF-IR blocking antibody alphaIR3 into mice harboring parental U87 tumors
      inhibits tumor growth and increases apoptosis. CONCLUSION: Inhibition of an
      upstream growth factor signal prevents tumor growth of the U87 PTEN-deficient
      glioma to the same extent as re-introduction of PTEN. This result suggests that
      growth factor receptor inhibition may be an effective alternative therapy for
      PTEN-deficient tumors.

PMID- 12057027
TI  - The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism
      following treatment with paroxetine: a PET study.
AB  - Several neuroimaging studies of patients with OCD have pointed to basal ganglia
      and the frontal cortical regions being relevant for an understanding of the
      pathophysiology and therapy of OCD. In a search for the neural substrate
      underlying the therapeutic action of paroxetine in the therapy of OCD we measured
      regional glucose metabolism in a PET study of 20 OCD patients before and after at
      least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to
      measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed
      patients fulfilling DSM-IV criteria for OCD. Patients were studied before and
      after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine.
      Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS) was performed before the first and after the second study. The PET data was
      analysed regionally using statistical parametric mapping (SPM-96). A clinical
      improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There
      was no difference in global cerebral metabolism before and after treatment
      whereas a post-treatment reduction in normalized rCMRglc was found in the right
      caudate nucleus. This finding also showed a significant positive correlation with
      symptom severity. Our results support hypotheses regarding a malfunction of the
      cortico-striato-thalamic system in the pathophysiology of OCD and particularly
      point to the caudate nucleus playing an important role for the therapeutic action
      of paroxetine in the treatment of OCD.

PMID- 12057028
TI  - Saturation of striatal D(2) dopamine receptors by clozapine.
AB  - Positron emission tomography (PET) studies have demonstrated low striatal D2
      dopamine receptor occupancy in clozapine-treated schizophrenic patients. The aim
      of this pilot study was to explore if this low receptor occupancy indeed
      represents partial saturability of striatal D2 dopamine receptors by clozapine.
      Three anaesthetized Cynomolgus monkeys were examined during one day with PET and
      [11C]raclopride at baseline and after intravenous injections of clozapine 1.5
      mg/kg followed by 18.5 mg/kg. The estimated corresponding human oral doses were
      approx. 210 mg/d and 2800 mg/d. D2 dopamine receptor occupancy was calculated
      using an equilibrium-ratio analysis and ranged from 54 to 58% after 1.5 mg/kg and
      87 to 89% after the total dose 20 mg/kg. The calculated maximal occupancy was
      93%. We conclude that PET-measured D2 dopamine receptor occupancy by clozapine
      can be described using a model based on the law of mass action, previously
      validated for conventional antipsychotics. Therefore, sufficiently high doses of
      clozapine are expected to produce complete striatal D2 dopamine receptor
      occupancy. The findings further support our previous findings of low D2 dopamine
      receptor occupancy in patients treated with standard doses of clozapine.

PMID- 12057029
TI  - Influence of monoamine oxidase A and serotonin receptor 2A polymorphisms in SSRI
      antidepressant activity.
AB  - The aim of the present study was to test a possible effect of the monoamine
      oxidase A (MAOA) and serotonin receptor 2A (5-HT-2A) gene variants on the
      antidepressant activity of fluvoxamine and paroxetine in a sample of major (n =
      248) and bipolar (n = 195) depressives, with or without psychotic features. A
      total of 443 in-patients were treated with 300 mg fluvoxamine (n = 307) or 20-40
      mg paroxetine (n = 136) for 6 wk. The severity of depressive symptoms was
      assessed weekly with the Hamilton Rating Scale for Depression (HAMD). Allele
      variants were determined in each subject using a PCR-based technique. We observed
      a marginal association between 5-HT-2A variants and antidepressant response while
      MAOA genotypes were not associated. Possible stratification factors, such as sex,
      diagnosis, presence of psychotic features, HAMD scores at baseline, pindolol
      augmentation and SSRIs plasma levels did not significantly influence the observed
      results. The investigated MAOA and 5-HT-2A gene variants, therefore, do not seem
      to play a major role in SSRI antidepressant activity.

PMID- 12057030
TI  - Down-regulation of platelet imidazoline-1-binding sites after bupropion
      treatment.
AB  - An elevation of I1 (imidazoline-1)-binding sites on platelets may be a state
      marker for depression. Herein, platelet I1 sites were compared in two groups of
      unipolar depressed patients given different regimens of bupropion treatment:
      Regimen 1 (n = 13 titrated up to 300 mg/d by week 4 and held constant until week
      6); Regimen 2 (n = 15 titrated up to 300 mg/d by week 2, to 450 mg/d by week 6,
      and held constant until week 8). Platelet I1 sites were quantified by p
      [125I]iodoclonidine binding (0.5-15 nM) and displaced by moxonidine under a
      saturating concentration of norepinephrine to mask alpha2-adrenoceptors. I1 B max
      values were confirmed to be high at pretreatment in depressed patients (n = 28)
      compared to healthy control subjects (n = 18; p = 0.02). Highest B max values at
      pretreatment were found in patients who responded worst to treatment. More than
      two-thirds of patients recovered from depression (69 and 80% in Regimens 1 and 2,
      respectively) after treatment. Dose and/or time of exposure to bupropion were
      relevant variables since (1). only Regimen 2 led to platelet I1 down-regulation
      and (2). the extent of down-regulation correlated with plasma concentrations of
      bupropion. The data suggest a dissociation exists between I1 down-regulation and
      therapeutic response, or else platelet I1 down-regulation lags behind clinical
      antidepressant response before becoming measurable.

PMID- 12057031
TI  - Time-course of hepatic cytochrome p450 subfamily induction by chronic
      carbamazepine treatment in rats.
AB  - Recent studies indicate that carbamazepine (CBZ) induces hepatic cytochrome p450
      (CYP) protein subfamilies. The present study examines the time-course of the
      appearance of hepatic CYP subfamilies (2B, 3A) and serum levels of CBZ and its
      metabolite, CBZ epoxide (CBZE), induced by CBZ treatment in rats. Male Wistar
      rats were given 5 g of CBZ (CBZ-treated) per 1 kg of feed for 3, 7, 14, 28 and 42
      d or feed without CBZ (control). Serum levels of CBZ and CBZE were evaluated by
      HPLC. Induction ratios of CYP2B and CYP3A were evaluated by Western blotting.
      Serum levels of CBZ and CBZE became maximal after 14 and 7 d, respectively, after
      CBZ treatment. Both levels gradually, then significantly decreased after 42 d CBZ
      compared with maximal levels. The induction ratio of CYP2B did not differ between
      3, 7, 14, 28 and 42 d CBZ treatment. The induction ratio of CYP3A reached a
      maximum after 14 d CBZ, then significantly decreased after 28 and 42 d CBZ
      compared to the maximal rate. The difference between CYP2B and CYP3A induction by
      CBZ chronic treatment is a novel finding.

PMID- 12057032
TI  - Effects of sigma ligands on NMDA receptor function in the bulbectomy model of
      depression: a behavioural study in the rat.
AB  - Sigma (sigma) ligands have been shown to modulate NMDA receptor activity. In the
      present study we used the olfactory bulbectomy (OBX) animal model of depression
      to assess the effects of the sigma1 ligand igmesine on OBX-induced behaviour.
      Behavioural experiments demonstrated OBX (saline-treated) rats to have increased
      dizocilpine-induced behavioural modifications, including locomotor and circling
      activity as compared to Sham rats (saline-treated). A short-term (7 d) treatment
      with low doses of igmesine (50-200 microg/kg.d s.c.) had no effect on dizocilpine
      induced behaviour while long-term treatments (14 d) with low doses of igmesine
      reversed the effect of the bulbectomy such that the treated OBX rats' behaviour
      was not significantly different from Sham-saline rats. Short-term treatments with
      high doses of igmesine (500-1000 microg/kg.d) also reversed the increased
      locomotor and circling behaviour seen in OBX rats (saline-treated) while long
      term treatments with the same high doses did not. These results provide
      behavioural evidence for sigma ligand's potential to reverse some OBX-induced
      behaviours. Moreover, they support the notion of a bell-shaped dose-response
      curve previously reported for sigma ligands.

PMID- 12057033
TI  - Sequential catecholamine and serotonin depletion in mirtazapine-treated depressed
      patients.
AB  - This study was aimed at determining whether patient- or antidepressant-related
      variables are most important to the mood response to serotonin (5-HT) or
      catecholamine depletion. Depressed patients treated with open-label mirtazapine
      (>or=6 wk) received two depletion tests (5-HT and catecholamine depletion) 1 wk
      apart. Both 5-HT and catecholamine depletion led to a partial return of
      depression in most patients. Antidepressant response to mirtazapine is dependent
      on its dual actions on norepinephrine and 5-HT neurotransmission. Mood response
      to tryptophan or catecholamine depletion is dependent on the pharmacological
      properties of the antidepressant being taken during depletion.

PMID- 12057034
TI  - Neuropsychiatric applications of transcranial magnetic stimulation: a meta
      analysis.
AB  - Transcranial magnetic stimulation (TMS) is a technology that allows for non
      invasive modulation of the excitability and function of discrete brain cortical
      areas. TMS uses alternating magnetic fields to induce electric currents in
      cortical tissue. In psychiatry, TMS has been studied primarily as a potential
      treatment for major depression. Most studies indicate that slow-frequency
      repetitive TMS (rTMS) and higher frequency rTMS have antidepressant properties. A
      meta-analysis of controlled studies indicates that this effect is fairly robust
      from a statistical viewpoint. However, effect sizes are heterogeneous, and few
      studies have shown that rTMS results in substantial rates of clinical response or
      remission, and the durability of antidepressant effects is largely unknown. We
      review in detail rTMS studies in the treatment of depression, as well as
      summarize treatment studies of mania, obsessive-compulsive disorder, post
      traumatic stress disorder, and schizophrenia. We also review the application of
      TMS in the study of the pathophysiology of psychiatric disorders and summarize
      studies of the safety of TMS in human subjects.

PMID- 12057035
TI  - Serotonin syndrome - 'potential' role of the CYP2D6 genetic polymorphism in
      Asians.

PMID- 12057036
TI  - Possible role of the endogenous opioid system in the placebo response in
      depression.

PMID- 12057038
TI  - Overview: gemcitabine as single-agent therapy for advanced breast cancer.
AB  - Breast cancer is one of the most common cancers worldwide. Various therapies,
      such as hormonal therapy, chemotherapy, and biologic therapies, can increase cure
      rates in the early-stage setting and improve survival and quality of life in
      specific advanced-disease settings. For advanced disease, the optimal timing,
      type, and combination of drugs remain to be defined. Gemcitabine is a newer agent
      with a unique mode of action that involves DNA chain termination and mechanisms
      that result in self-potentiation. This results in a broad spectrum of activity in
      many types of solid tumors including breast cancer. As a single agent,
      gemcitabine yields response rates ranging from 14%-37% as first-line therapy for
      advanced breast cancer and 23%-42% as salvage therapy. However, these were small
      studies with large confidence intervals around all the indices of benefit
      including response rate, response duration, and time to disease progression.
      Gemcitabine was associated with higher response rates when used in combination
      with other agents. The side-effect profile of gemcitabine has been favorable
      compared to that of commonly used cytotoxic drugs, and includes myelosuppression
      and fatigue, with a notable absence of alopecia and gastrointestinal symptoms.
      Larger ongoing studies will help define the utility of gemcitabine in advanced
      breast cancer

PMID- 12057039
TI  - Preclinical studies of gemcitabine and trastuzumab in breast and lung cancer cell
      lines.
AB  - Overexpression of the HER2/neu oncogene and receptor protein has been reported in
      20%-30% of patients with breast cancer and is associated with a poor prognosis.
      HER2/neu expression in breast cancer patients assessed by fluorescence in situ
      hybridization or immunohistochemistry is a predictor for response to trastuzumab,
      a humanized monoclonal antibody against the HER2/neu cell-surface protein. Data
      regarding HER2/neu expression in lung cancer are more limited, and there is
      little information regarding HER2/neu expression and response to trastuzumab
      alone or in combination with chemotherapeutic agents. Gemcitabine is an active
      agent against non-small-cell lung cancer (NSCLC) and has demonstrated activity in
      breast cancer as well. In vitro modified tetrazolium salt growth assays were
      performed to determine whether the combination of trastuzumab/gemcitabine
      produced synergistic or additive effects on breast and lung cancer cell lines.
      The effects of trastuzumab alone, gemcitabine alone, and the
      trastuzumab/gemcitabine combination was evaluated on 4 NSCLC cell lines, 1 small
      cell lung cancer (SCLC) cell line, and 2 breast cancer cell lines. HER2/neu
      surface protein expression was assessed by fluorescence flow cytometry and
      immunohistochemistry. Fluorescence in situ hybridization analysis was used to
      study gene expression. Trastuzumab treatment alone resulted in growth inhibition
      in all cell lines expressing HER2/neu and the inhibitive effect correlated with
      the level of cell surface HER2/neu protein expression. Treatment with gemcitabine
      alone resulted in growth inhibition in both breast and NSCLC cell lines. A
      synergistic growth inhibition effect was seen with the trastuzumab/ gemcitabine
      combination as indicated by combination index values < 1. The degree of synergy
      observed did not directly correlate with the level of surface protein expression,
      as synergy was seen even in cancer cell lines expressing low levels of HER2/neu.
      No treatment effect was seen in the SCLC cell line, which did not express
      HER2/neu. These preclinical studies indicate a need to study the clinical
      synergistic effects of the gemcitabine/trastuzumab combination in breast cancer
      and NSCLC patients whose tumors overexpress HER2/ neu.

PMID- 12057040
TI  - Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer
      patients previously treated with chemotherapy: preliminary results.
AB  - Preliminary results of a phase II study of gemcitabine plus trastuzumab in
      previously treated (up to 3 previous regimens) metastatic breast cancer patients
      are presented. Patients had histologically confirmed metastatic breast cancer,
      with 2+ or 3+ tumor HER2 expression. Treatment consisted of gemcitabine 1200
      mg/m2 over 30 minutes intravenously on days 1 and 8 every 21 days, and
      trastuzumab 4 mg/kg over 90 minutes, followed by 2 mg/kg infused over 30 minutes
      weekly. Treatment was continued until disease progression or unacceptable
      toxicity occurred. Preliminary results are available on the first 38 patients
      enrolled. Median patient age was 53 years, 53% had estrogen receptor/progesterone
      receptor-positive disease, and HER2 staining was 2+ in 39% and 3+ in 61% of
      patients. There was a median of 3 previously administered (including adjuvant)
      chemotherapy regimens, and a median of 4.5 treatment cycles per patient has been
      administered so far. Twelve patients (32%) have had an objective partial
      response, with a median response duration of 8.6 months. Median time to disease
      progression is 6.7 months to date, with a median overall survival of 10.2 months.
      No unexpected toxicities or grade 4 nonhematologic toxicities have been observed;
      2 patients developed grade 4 neutropenia and 1 patient had febrile neutropenia.
      Thus, gemcitabine/ trastuzumab resulted in an encouraging 32% response rate,
      given the heavily pretreated patient population. Tolerability was good overall,
      with no unexpected side effects observed.

PMID- 12057041
TI  - Pemetrexed (Alimta) and gemcitabine in breast cancer patients previously treated
      with anthracyclines and taxanes.
AB  - Gemcitabine (2',2'-difluorodeoxycytidine) is a pyrimidine antimetabolite with
      broad activity in a variety of solid tumors including breast cancer. Pemetrexed
      (Alimta) is a novel, multitargeted antifolate that inhibits 3 folate-dependent
      enzymes, and is also broadly active in a wide variety of solid tumors. In breast
      cancer, pemetrexed has activity in patients previously treated with
      anthracyclines and taxanes, and pemetrexed demonstrates preclinical and clinical
      cytotoxic synergy with gemcitabine. This drug combination is being evaluated in a
      phase II study for the treatment of metastatic breast cancer patients who have
      previously received a taxane and an anthracycline.

PMID- 12057042
TI  - Gemcitabine plus cisplatin for the treatment of metastatic breast cancer.
AB  - The combination of gemcitabine and cisplatin has proven effective as first-line
      chemotherapy for patients with breast cancer, inducing a response rate of 80% in
      one phase II study. Five additional studies in intensively pretreated breast
      cancer patients demonstrated a median response rate of 43% (range, 26%-50%). The
      toxicity profile was moderate, with thrombocytopenia and neutropenia as the main
      side effects. The gemcitabine/ cisplatin combination, therefore, offers a
      tolerable and effective treatment option, particularly for patients whose disease
      progressed after treatment with anthracyclines and/or taxanes.

PMID- 12057044
TI  - Gemcitabine in combination with vinorelbine for treatment of advanced breast
      cancer.
AB  - Several cytotoxic drugs have substantial antitumor activity against breast
      cancer. Combination cytotoxic regimens are associated with higher response rates
      and longer durations of response and survival than single-agent regimens.
      However, combination regimens of conventional agents have not changed the course
      of advanced disease. Since 1990, several newer cytotoxic agents have been
      developed and integrated into management strategies for advanced breast cancer.
      Gemcitabine and vinorelbine are 2 such newer cytotoxic agents that have
      demonstrated promising antitumor activity and favorable toxicity profiles as
      single-agent therapy for metastatic breast cancer. Gemcitabine and vinorelbine
      have different mechanisms of antitumor activity, good therapeutic indices, and
      nonoverlapping toxicities. The combination of these 2 drugs has been evaluated
      for the treatment of advanced breast cancer. Preliminary results from phase II
      clinical trials suggest that gemcitabine/vinorelbine with or without granulocyte
      colony-stimulating factor is effective first- or second-line therapy for advanced
      breast cancer and has a favorable safety profile. Further studies of the
      gemcitabine/ vinorelbine combination regimen are warranted

PMID- 12057043
TI  - Gemcitabine/anthracycline combinations in metastatic breast cancer.
AB  - Gemcitabine has demonstrated single-agent efficacy in the treatment of advanced
      breast cancer, with response rates of up to 42%. The agent is well tolerated,
      with relatively mild side effects, and has limited overlapping toxicities with
      other drugs used in combination chemotherapy for breast cancer. It is, therefore,
      a good candidate for inclusion in multidrug regimens for the treatment of this
      disease. This article reviews results of gemcitabine/anthracycline-containing
      double- and triple-drug combinations used to treat patients with early-stage and
      advanced breast cancer. Results from phase I and II trials were promising, with
      good tolerability and overall response rates ranging from 33%-89% in advanced
      disease and up to 95% in the neoadjuvant treatment of early-stage disease. A
      phase III trial is currently comparing gemcitabine/epirubicin/paclitaxel and 5
      fluorouracil/epirubicin/cyclophosphamide in patients with advanced breast cancer.
      Preliminary toxicity data on 78 patients show that both regimens were well
      tolerated, with similar incidences of treatment-related effects. Additional
      comparative studies of gemcitabine-containing drug regimens in breast cancer are
      warranted.

PMID- 12057045
TI  - Neoadjuvant gemcitabine therapy for breast cancer.
AB  - Neoadjuvant chemotherapy has become a standard treatment in the management of
      locally advanced breast cancer. Patients with earlier-stage disease may also
      benefit from neoadjuvant treatment in terms of improved rates of breast
      conserving surgery and thus better quality of life. Gemcitabine is a pyrimidine
      analogue that has shown activity in a variety of solid tumors, a good toxicity
      profile, and nonoverlapping toxicity with other chemotherapeutic agents. Several
      phase II/III studies are assessing gemcitabine combined with anthracyclines,
      taxanes, and/or vinorelbine both in the neoadjuvant and metastatic disease
      settings. This article reviews developments in neoadjuvant use of gemcitabine in
      combination with anthracyclines and taxanes. Several phase II trials of
      gemcitabine combined with doxorubicin/epirubicin or with doxorubicin/paclitaxel
      have been carried out. Preliminary findings demonstrate increased complete
      response rates and good tolerability of these regimens in patients with breast
      cancer.

PMID- 12057046
TI  - Gemcitabine in breast cancer: future directions.
AB  - Gemcitabine is an active drug in advanced breast cancer both as a single agent
      and in combination with other chemotherapeutic agents. Its unique mechanisms of
      action, which involve masked DNA chain termination and several self-potentiating
      effects on DNA and RNA synthesis enzymes, result in broad and potent activity
      across many cancer types. Preclinical models have suggested positive interactions
      with other agents such as trastuzumab, and early-phase clinical trials are
      exploring potential synergistic activity with another DNA-synthesis targeting
      drug, the multitargeted antifolate, pemetrexed (Alimta). Many small trials have
      confirmed the efficacy and tolerability of gemcitabine alone or in combinations
      with other drugs as summarized in this supplement. Furthermore, neoadjuvant
      clinical models have shown promising pathologic complete response rates, an
      endpoint that correlates with prolonged survival. These results taken together
      have now set the stage for more definitive phase III trials of gemcitabine
      combinations compared to standard combinations that will directly assess the
      independent contribution of gemcitabine. In the metastatic setting, survival
      benefits (if any) are likely to be limited, but the potential to achieve this
      with preservation of quality of life is good. Synergistic combinations with
      biological therapies or novel chemotherapeutic agents need to be further
      explored, and ultimately, randomized trials will be needed to define optimal
      regimens. The largest clinical benefits might be derived from the proper
      deployment of gemcitabine combinations with taxanes and/or anthracyclines in the
      adjuvant setting. Highly active and well-tolerated therapies, especially those
      that are justified based on preclinical and neoadjuvant models, represent our
      best hope for successors to current adjuvant regimens. Such trials are now either
      in the planning stages or already under way.

PMID- 12057048
TI  - Symptomatic cryoglobulinemia.
AB  - 1. Treatment of symptomatic cryoglobulinemia is exceedingly challenging due to
      the multisystemic nature of its presentation, the variability of its course, and
      the paucity of effective therapeutic options supported by randomized controlled
      clinical trials. 2. Patients with mild, relatively asymptomatic disease should be
      observed without introduction of systemic therapy. 3. Patients with symptomatic
      type I secondary cryoglobulinemia should be treated as appropriate for their
      underlying lymphoproliferative or plasmaproliferative disorder. 4. Patients with
      secondary type II or type III cryoglobulinemia should be treated for their
      underlying connective tissue, lymphoproliferative, or liver disorder or
      infection. 5. First line treatment for symptomatic, essential type II or type III
      cryoglobulinemia associated with hepatitis C should include interferon (IFN)
      alpha. Depending on the severity of clinical presentation, adjuvant
      corticosteroids or plasmapheresis should be considered. 6. Life-threatening or
      acute organ-threatening presentations should be managed with combined modality
      therapy, which should include high-dose corticosteroid, plasmapheresis, or
      alkylator-based therapy. 7. Many chemotherapeutic and immunosuppressive
      strategies have been tried but not systematically tested; their value is
      therefore unknown. 8. Challenges for the future of treating symptomatic
      cryoglobulinemia include devising better therapies and more systematic evaluation
      of existing therapies.

PMID- 12057047
TI  - Waldenstrom's macroglobulinemia.
AB  - Waldenstrom's macroglobulinemia (WM) is a clinical syndrome with diverse
      prognoses, and not all patients require therapy at diagnosis. Serum beta2
      microglobulin is a major prognostic determinant, and asymptomatic patients with
      low beta2 microglobulin levels and preserved hemoglobin can be observed over long
      periods without therapy. Low-dose alkylating agents and purine analogs are
      commonly employed as initial therapy but rarely yield complete remissions.
      Patients who are refractory to or have relapse after alkylator or purine analogue
      therapy can be salvaged with purine analogs. Improvement in outcome demands a
      comprehensive approach aimed at increasing and sustaining complete remissions.
      Such an approach should probably employ Rituxan (IDEX Pharmaceuticals, La Jolla,
      CA) in conjunction with induction therapy, peripheral stem cell procurement
      before purine analog therapy, and high-dose therapy followed by maintenance
      therapy with interferon.

PMID- 12057049
TI  - Smoldering, asymptomatic stage 1, and indolent myeloma.
AB  - Of patients presenting with multiple myeloma, 5% to 15% satisfy criteria for the
      diagnosis of multiple myeloma but have no or minimal symptoms and do not require
      chemotherapy (NRC). These patients are classified as having smoldering,
      asymptomatic stage 1, or indolent multiple myeloma in order of their increasing
      risk of progression. We avoid chemotherapy, especially with alkylating agents in
      such patients, and we either closely monitor them or use a nonchemotherapeutic
      intervention. If significant bone lesions, renal failure, or hypercalcemia occur,
      chemotherapy or transplant is recommended. Patients with mild anemia or with
      small or isolated bone lesions who are asymptomatic or minimally symptomatic
      because of anemia may be monitored and are classified as having indolent multiple
      myeloma. Unnecessary treatment with melphalan or cyclophosphamide probably has no
      benefit in multiple myeloma NRC and can cause significant risk. In long-term
      follow up, 25% of patients receiving alkylating agents develop myelodysplastic
      syndrome or acute leukemia. Patients who do not receive chemotherapy must be
      monitored closely to avoid complications of overt multiple myeloma, including
      anemia, bone lesions, renal failure, and hypercalcemia. We and others have begun
      to take a more active approach with the use of nonchemotherapeutic agents in
      selected patients. We use bisphosphonates in patients with bone lesions or
      osteoporosis or when there is a progressive rise in M-protein. We use
      dexamethasone alone in NRC multiple myeloma to reduce tumor burden in selected
      patients who do not yet have overt multiple myeloma or who are not candidates for
      chemotherapy. We use bisphosphonates to prevent osteoporosis in such patients. We
      use erythropoietin to correct anemia, and dexamethasone and erythropoietin
      together in patients with higher tumor burden (eg, indolent multiple myeloma).
      Future progress in treating multiple myeloma NRC depends on better identification
      of new therapeutic targets that control progression from the stable asymptomatic
      to the progressive symptomatic phase of multiple myeloma. We need to better
      understand the biologic target of new agents like thalidomide to design more
      effective treatment for this early phase of multiple myeloma. Although these
      approaches may delay chemotherapy, it is not known whether survival is prolonged.
      Nonchemotherapeutic approaches must be systematically studied in clinical trials
      in order to be put to better use.

PMID- 12057050
TI  - Early ovarian cancer.
AB  - Epithelial ovarian cancer may appear to be confined to the ovaries or pelvis in
      approximately one-third of patients at exploration, but up to 30% of them will be
      upstaged following surgical staging. Substage and histotype are the most
      important prognostic factors that determine the need for adjuvant treatment.
      Patients with stage Ia or Ib and well-differentiated (other than clear cell)
      tumors do not require adjuvant treatment. Patients with stage Ia or Ib grade 3 or
      clear cell histology, as well as any stage Ic and II disease, are at high risk
      for recurrence. Platinum-based chemotherapy is the mainstay of treatment. Four to
      six courses are probably adequate, although grade 3 tumors may require further
      treatment. Preservation of the uterus and the uninvolved contralateral ovary is a
      viable option in young women with unilateral early disease.

PMID- 12057052
TI  - Early cervical cancer.
AB  - Early cervical cancer includes a broad range of disease, from clinically
      undetectable microinvasive cancer to large, bulky tumors that replace the entire
      cervix. Further subgrouping of this category is therefore necessary to define the
      optimal treatment approach for individual cases. The International Federation of
      Gynecology and Obstetrics (FIGO) staging system stratifies stage I tumors into
      two broad categories, stage IA (microinvasive) and stage IB (gross tumor).
      Management of women with stage IA disease is controversial. In the United States,
      patients with stromal invasion of less than 3 mm and no lymphvascular involvement
      are usually treated conservatively with simple hysterectomy. In selected patients
      who desire fertility, cone biopsy with negative surgical margins is also
      considered. Patients with invasion of more than 3 mm or lymphvascular space
      involvement are at risk for pelvic lymph node metastasis and are most often
      treated with radical hysterectomy and pelvic lymphadenectomy. Stage IB1 cervical
      cancer is managed by either radical surgery or radiotherapy with equivalent
      recurrence and survival rates. In patients with tumors less than 4 cm in
      diameter, the decision between radical surgery and radiotherapy is guided by
      patients' overall health and treatment preferences. For younger women, radical
      surgery is preferred because ovarian function can be preserved and vaginal
      stenosis secondary to radiation can be avoided. Radiation therapy is preferred
      for women who may not tolerate radical surgery. We always prefer primary
      radiation therapy for patients with tumors larger than 4 cm in diameter. Recent
      data convincingly demonstrate that the addition of cisplatin-based chemotherapy
      significantly improves overall survival rates in cervical cancer patients who
      undergo radiation therapy.

PMID- 12057051
TI  - Advanced ovarian cancer.
AB  - State-of-the-art treatment for advanced ovarian cancer requires a multimodality
      approach. Aggressive surgical debulking with the goal of optimal cytoreduction is
      the initial step. After primary cytoreductive surgery, standard treatment for
      patients with stage III and IV disease is systemic combination chemotherapy
      consisting of six cycles of paclitaxel and carboplatin. Approximately 70% of
      patients enter a clinical remission with this approach, yet less than 30% remain
      disease free. Options following primary therapy include observation or second
      surgical assessment if no clinical evidence of disease is present. Novel
      strategies for consolidation are needed. Second-look surgery can be performed
      safely and effectively laparoscopically, and this is the most accurate means of
      identifying patients who appear to be clinically free of disease but actually
      harbor persistent cancer. Although this procedure is an extremely accurate means
      of identifying these patients, women who have pathologically negative second-look
      surgery are still at risk for relapse. Patients can receive additional treatment
      following second-look surgical assessment via the intraperitoneal route if they
      are pathologically negative or if they have microscopic or small volume disease.
      Alternatively, additional systemic chemotherapy can be given with non-cross
      resistant systemic agents, but no current standard approach for consolidation
      therapy exists for patients following the completion of primary treatment.
      Unfortunately, most patients relapse. Multiple agents with similar activity in
      phase II trials are available to treat patients with advanced recurrent disease.
      Combination therapy in this setting has not been shown to have significantly
      superior progression-free or overall survival compared with single agents. The
      selection of treatment for patients with recurrent disease is currently based on
      a determination of the treatment-free interval since last treatment, as well as
      the route, schedule, and expected side effects of the agent.

PMID- 12057053
TI  - Advanced cervical cancer.
AB  - Several large, prospectively randomized clinical trials run by multi
      institutional cooperative groups have established that the best treatment for
      advanced cancer of the cervix is primary radiotherapy with concurrent, cisplatin
      based chemotherapy. In fact, patients with earlier stage cervix cancer with poor
      prognostic indicators (large, bulky tumors, positive pelvic lymph nodes, or
      unexpected parametrial disease at the time of surgery) also show a survival
      benefit with this approach. Adequate radiation dosing (both external beam and
      intracavitary) is essential. The additional benefit of periaortic lymph node
      irradiation is debated, but generally accepted, for patients with locally
      advanced disease or pelvic lymph node involvement.

PMID- 12057054
TI  - Uterine/female genital sarcomas.
AB  - Choosing the best management of uterine and vulvo-vaginal sarcomas depends on
      careful histologic review of the pathologic specimen. Prognosis and treatment
      vary greatly depending on specific histology, grade, and tumor stage. The initial
      approach to sarcomas of the female genital tract, with the occasional exception
      of vulvo-vaginal rhabdomyosarcoma, is surgery. Adjuvant radiation decreases local
      recurrence rates for uterine sarcomas, but has not been clearly shown to improve
      overall survival. It is frequently used as adjuvant therapy for resected high
      grade or margin-positive vulvo-vaginal sarcomas, and for endometrial stromal
      sarcomas. Adjuvant chemotherapy has not been demonstrated to improve survival in
      vulvo-vaginal sarcomas, with the exception of vulvo-vaginal rhabdomyosarcomas,
      nor has it been demonstrated to improve survival in uterine sarcomas.
      Chemotherapy may be used for recurrent or persistent disease. The choice of agent
      depends on the histologic type of sarcoma.

PMID- 12057055
TI  - Gestational trophoblastic disease.
AB  - Patients diagnosed with molar pregnancy are treated by either suction curettage
      or hysterectomy, depending on their desire to preserve fertility. We use single
      agent chemotherapy, preferably methotrexate, to treat low- or moderate-risk
      persistent trophoblastic tumors. High-risk patients who have metastatic disease
      are treated primarily with combination chemotherapy and, as indicated, adjuvant
      radiotherapy or surgery. We perform a hysterectomy in all cases of placental-site
      trophoblastic tumors; combination chemotherapy is used if there is evidence of
      metastatic disease.

PMID- 12057056
TI  - Vulvar carcinoma.
AB  - Carcinoma of the vulva is an uncommon gynecologic malignancy primarily affecting
      postmenopausal women. The lesion is most commonly associated with HPV DNA,
      although, for many, a defined preinvasive to invasive connection is not readily
      apparent. Most patients experience symptoms of pruritus, irritation, and even
      pain for weeks or months before the diagnostic biopsy is performed. Patient
      embarrassment and unfamiliarity and reluctance on the part of the physician to
      fully evaluate these symptoms add to the delay. Vulvar carcinoma is staged
      surgically following resection. A concerted effort to conserve as much normal
      tissue as possible has been the focus of recent investigation. Separate incision
      resection of the vulvar mass and groin has improved wound healing and quality of
      life for many patients. The effect these conservative procedures have on long
      term survival is currently being evaluated. Increased use of radiation therapy or
      chemoradiation has allowed organ preservation in many otherwise exenterative
      cases. In some instances, this neoadjuvant therapy has provided an opportunity to
      surgically clear otherwise unresectable lesions. Current radiotherapy techniques
      might also be as effective as groin dissection in certain low-risk patients.
      Adjuvant radiation and chemoradiation improve local control and reduce groin
      recurrence risk. In addition, patients with histologically positive groins enjoy
      longer survival when the pelvis is also treated. Selected use of multimodality
      therapy will likely extend the lives of women with vulvar cancer.

PMID- 12057057
TI  - Acute myeloid leukemia in adults.
AB  - The treatment outcome for most adults with acute myeloid leukemia (AML) remains
      unacceptable. Additional agents or substitution of high-dose cytarabine for
      conventional-dose cytarabine during induction does not improve the remission rate
      or overall survival. There is substantial toxicity with high-dose cytarabine
      during induction. Thus, induction therapy for newly diagnosed patients with AML
      should consist of cytarabine (100 mg/m(2) as a continuous intravenous infusion
      over 24 hours for 7 days) and daunorubicin, idarubicin, or mitoxantrone. Meta
      analysis demonstrates a modest benefit for idarubicin. Most patients who achieve
      a remission should receive further therapy with two to four cycles of high-dose
      cytarabine. Allogeneic stem cell transplant is reserved for patients with poor
      risk features. There is no role for autologous stem cell transplant in first
      remission outside a clinical trial. The majority of adults relapse. Salvage
      therapy usually consists of high-dose cytarabine. Allogeneic or autologous stem
      cell transplantation is preferred in second or subsequent remission. Uncommon
      diseases such as AML, for which the outcome remains poor, should be treated on
      clinical trials whenever possible.

PMID- 12057058
TI  - Acute lymphoblastic leukemia in adults.
AB  - The therapy of acute lymphoblastic leukemia (ALL) in adults has built on the
      remarkable success achieved in the treatment of this disease in children.
      However, older age and other adverse risk factors seen more commonly in adults
      than in children have lessened the success of the treatment of ALL in comparison
      with what has been achieved in children. The treatment of ALL depends on the use
      of intensive multi-agent chemotherapy given over 6 to 9 months in combination
      with central nervous system prophylactic therapy with cranial radiation and
      intrathecal chemotherapy followed by maintenance chemotherapy for 2 to 3 years.
      This therapy has allowed younger patients with newly diagnosed ALL to achieve
      complete remission in 80% to 90% of cases, but has still resulted in subsequent
      relapse in most patients. For high-risk patients with ALL, allogeneic blood and
      marrow transplant (BMT) from a related or unrelated donor can improve the outcome
      compared with chemotherapy. The role of autologous transplantation in ALL remains
      uncertain, as does the role of allogeneic transplant in standard-risk patients.
      This issue continues to be the subject of large, randomized trials. New agents
      and improvements in supportive care bring the hope that more patients with ALL
      will be cured in the future.

PMID- 12057059
TI  - Acute promyelocytic leukemia.
AB  - The treatment of acute promyelocytic leukemia (APL) is different from other
      subtypes of acute myelocytic leukemia (AML). All trans-retinoic acid (ATRA) is an
      essential component of the standard remission induction for all newly diagnosed
      APL patients. Remission induction with ATRA and chemotherapy given concurrently
      appears to be associated with fewer relapses. With further consolidation
      chemotherapy without high-dose cytosine arabinoside, the disease-free survival
      rate can reach 70% to 80%, and many of these patients are cured, more so than in
      any other AML subtype. APL is especially sensitive to anthracyclines, which
      should be included in the chemotherapy cycles at a higher dose than in other AML
      subtypes. Maintenance with low-dose chemotherapy (oral daily 6-mercaptopurine
      with weekly methotrexate) or ATRA further improves the long-term outcome. New
      approaches are also available for relapsing patients, although the optimal
      treatment is unknown. Patients who did not receive oral ATRA in first relapse can
      be treated with this agent, as can first relapsing patients who have been off the
      drug for more than 1 year. Because of poor remission rates, ATRA should not be
      used in patients with second or subsequent relapses (whether ATRA was given in
      the past), in patients with relapses early after ATRA discontinuation, or in
      patients relapsing while on ATRA therapy. Arsenic trioxide can also be used,
      especially in patients resistant to ATRA. Because arsenic trioxide is still
      experimental and not yet widely available, patients who are unlikely to respond
      to ATRA or who unsuccessfully undergo ATRA reinduction should be treated with
      chemotherapy. Patients in second or subsequent remission induced with ATRA or
      chemotherapy should receive consolidation chemotherapy. When arsenic trioxide is
      used for reinduction, the drug should be continued for several cycles; however,
      adding consolidation chemotherapy might improve the results. Because it is
      unknown whether APL in second or subsequent remission is curable with salvage
      therapy, allogeneic hematopoietic stem cell transplantation is often considered
      for patients with a human leukocyte antigen (HL-A)-identical sibling and
      autologous transplantation when a donor does not exist. However, compared with
      the new treatments, the role of transplantation for relapse is unclear. In first
      remission, there is no role for transplantation. A new liposomal formulation of
      intravenous ATRA is being investigated and seems effective in late first
      relapses, and it may be able to induce and maintain first remissions in selected
      patients without chemotherapy.

PMID- 12057060
TI  - Cutaneous T-cell lymphoma/leukemia.
AB  - Effective treatment for cutaneous T-cell lymphomas (CTCL) requires an accurate
      and specific diagnosis based on the clinical presentation combined with
      evaluation of the histopathology, immunophenotyping, and gene rearrangement
      studies. Careful clinical and pathologic evaluation in centers familiar with the
      diverse forms of CTCL is most valuable for determining treatment options. The
      goals of treatment in mycosis fungoides (MF), which afflicts more than 50% of
      patients with CTCL, are the relief of symptoms and improvement in cosmetics.
      Despite some uncontrolled clinical trial results that have been reported to
      suggest "cures" in this disease, the general perception remains that this disease
      is not curable with standard therapies available today. Treatment is divided into
      topical (skin-directed) and systemic therapy. The most active systemic agent for
      the treatment of MF remains interferon-alpha, although many new modalities have
      recently been approved for the treatment of CTCL.

PMID- 12057061
TI  - Accelerated and blastic phase of chronic myeloid leukemia.
AB  - There is currently no standard treatment for the blastic phase of chronic myeloid
      leukemia (CML-BC), which is a chemoresistant form of acute leukemia. Current
      approaches include using standard acute myeloid leukemia (AML) regimens in an
      effort to induce remission, variations of these approaches with drugs that seem
      more active in this specific leukemia, and the direct entry of patients into
      studies of investigational agents. Although the likelihood of achieving remission
      is small, immediate bone marrow transplantation in remission should be considered
      because it provides the only opportunity for long-term survival at this time.
      Allogeneic transplantation is preferred, but autologous transplantation of an
      early chronic phase marrow may provide benefit. Often, however, the duration of
      chemotherapy-induced remission of blast crisis is very short and may preclude
      entry into a transplant program. In addition, the patient may not be a candidate
      due to donor issues, age, or medical problems. If transplant is not an option,
      maintenance interferon is often used, although its benefit is uncertain. For
      patients in the accelerated phase of the disease, which is characterized by a
      variety of clinical presentations and cytogenetic abnormalities, the possibility
      of favorably manipulating the disease is greater. Again, there is no standard
      treatment, and clinical trials are recommended as first-line therapy. Treatment
      in the accelerated phase includes standard AML chemotherapy regimens,
      combinations of new agents, and the combination of cytostatic agents with
      interferon. Patients whose accelerated phase reverts to chronic phase after
      treatment may become candidates for bone marrow transplantation. However, current
      new approaches to the chronic phase applied in accelerated phase as well as new
      approaches directed specifically toward accelerated phase may lead to prolonged
      stabilization without bone marrow transplantation. In view of a median age of 55
      at diagnosis of chronic phase, nontransplant regimens for accelerated phase that
      produce long-term benefit are urgently needed.

PMID- 12057062
TI  - Myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders with a
      variable clinical course and prognosis. Treatment should be individualized based
      on the patient's age, subtype, percent blasts in the marrow, and cytogenetics.
      The use of the International Prognostic Scoring Index is helpful in assigning
      prognosis. The standard of care for low-risk patients is supportive care. Low
      risk patients with symptomatic anemia should be considered for a trial of
      erythropoietin. The serum erythropoietin (EPO) level may help predict response to
      treatment. The treatment of the symptomatic and high-risk patient is unclear. Low
      dose cytarabine, amifostine, and 5-azacitidine can induce responses in selected
      patients, but the duration of responses is short, and treatment does not appear
      to prolong survival. Intensive chemotherapy should be reserved for high-risk,
      younger patients. Topotecan and intermediate cytarabine appear to have an active
      regimen, but remissions are short. Younger patients who present with high-risk
      MDS without an antecedent history of MDS should receive intensive acute myeloid
      leukemia (AML) induction chemotherapy. Younger patients with high-risk MDS and an
      HLA-compatible donor should be offered an allogeneic stem cell transplant.

PMID- 12057064
TI  - Primary systemic amyloidosis.
AB  - Patients with unexplained heart failure, hepatomegaly, nephrotic syndrome, or
      peripheral neuropathy should be evaluated for primary systemic (amyloid light
      chain, or AL) amyloidosis by first seeking evidence of a clonal plasma cell
      disorder with serum and urine immunofixation studies, as well as a bone marrow
      biopsy. Immunostaining of the marrow biopsy for lambda and kappa isotypes will
      usually demonstrate a dominant clonal population of plasma cells if
      immunofixation studies are negative (less than 10% of cases). Tissue diagnosis of
      amyloidosis should be sought by biopsy of the abdominal fat or an involved organ.
      In addition, patients with stable myeloma or monoclonal gammopathy of
      undetermined significance who develop such conditions or become progressively ill
      should be evaluated for amyloidosis. We recommend that newly diagnosed patients
      with AL amyloidosis, who meet criteria for autologous hematopoietic cell
      transplantation, be considered for high-dose melphalan with stem cell support.
      Criteria usually include adequate cardiac, pulmonary, and hepatic function. AL
      amyloidosis patients treated with autologous transplantation frequently achieve
      durable complete remissions of the plasma cell disease and marked improvement in
      amyloid-related organ dysfunction. AL amyloidosis patients with dominant cardiac
      amyloid, who are without symptomatic pleural effusions and have no history of
      cardiac syncope or symptomatic arrhythmias, may be considered for autologous
      transplantation but are at increased risk of peritransplant mortality. Autologous
      transplantation should not routinely be offered to patients with dominant cardiac
      amyloid with recurrent effusions or histories of syncope or arrhythmias or to
      patients older than 50 years of age with more than two major organ systems
      involved (eg, heart, kidneys, liver, and peripheral nerves). We recommend that AL
      patients with isolated advanced cardiac or hepatic amyloidosis be considered for
      solid organ replacement followed by autologous transplantation. Otherwise, AL
      patients who are elderly or ineligible for autologous transplantation may be
      treated with oral melphalan (Alkeran, GlaxoWellcome, Middlesex, UK) and
      prednisone; however, because the response rate is only about 25% and the
      prognosis poor, such patients might also be enrolled on clinical trials of
      emerging therapies.

PMID- 12057063
TI  - Multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable plasma cell dyscrasia that remains fatal.
      Despite efforts over the past 3 to 4 decades, the median survival of patients
      with MM does not exceed 3 to 4 years. Although patients receiving combination
      chemotherapy have higher response rates compared with those receiving oral
      melphalan and prednisolone, they have no survival advantage. High-dose
      chemotherapy followed by autologous stem cell transplantation has documented
      benefit over conventional treatment and is currently the accepted mode of
      treatment for symptomatic MM. Allogeneic transplantation is associated with high
      complete remission rates, but at the cost of high therapy-related mortality.
      Maintenance treatment with interferon-alpha shows benefit, albeit in a small
      fraction of MM patients. The use of bisphosphonates in patients with MM has
      clearly demonstrated benefit and reduced morbidity associated with bone disease.
      All of these measures have improved remission rates and survival, but all
      patients with MM ultimately relapse and succumb to their disease. Novel
      therapeutic strategies are therefore required to improve outcome of MM patients.
      The responses noted to thalidomide in MM are encouraging. Immune-based
      strategies, including both adoptive immunotherapy and vaccinations, are currently
      being investigated in the preclinical and clinical setting, with the goal of
      enhancing autologous and allogeneic anti-MM immunity for therapeutic
      applications.

PMID- 12057065
TI  - Nonmelanoma skin cancer.
AB  - Therapy for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) does not
      end with treatment of the initial lesion because almost 50% of patients with one
      nonmelanoma skin cancer (NMSC) develop another NMSC in the next 5 years. An
      integrated program of skin cancer awareness, sun protection, and prophylactic
      approaches is critical. The risk profile of the tumor influences which therapies
      and specialties will be involved. Most NMSCs may be treated with outpatient
      methods. Primary care physicians may treat low-risk tumors, but dermatologists
      specially trained in cutaneous oncology and a multidisciplinary team should
      manage high-risk lesions. Superficial BCC and SCC may be treated adequately with
      superficial modalities such as electrodesiccation and curettage (EDC) and
      cryotherapy. Topical 5-fluorouracil is effective for small in situ lesions.
      Invasive but low-risk lesions may be treated with EDC and cryotherapy provided
      that the tumor is limited to the papillary dermis, is not recurrent, and does not
      have high-risk features. High-risk tumors are best treated with excision and
      histologic examination or Mohs micrographic surgery (MMS). MMS is the therapeutic
      gold standard for all NMSCs in terms of cure rates, margin control, and tissue
      conservation. Because of its higher cost and specialized process, MMS is best
      reserved for specific indications.

PMID- 12057067
TI  - Chronic myelomonocytic leukemia.
AB  - Chronic myelomonocytic leukemia (CMML) has dysplastic and proliferative features.
      The median age of patients with CMML is 70 years; the median survival is
      approximately 2 years. Various chemotherapy regimens have been used with only
      modest success. When the proliferative phase prevails, hydroxyurea is the
      treatment of choice. For younger patients with high-risk CMML, an allogeneic bone
      marrow transplantation should be considered. If a donor cannot be identified,
      then combination acute myeloid leukemia-type therapy followed by an autologous
      stem cell or marrow transplant should be offered. Clinical trials should be
      considered if available because the overall results of therapeutic interventions
      are far from optimal.

PMID- 12057066
TI  - Intermediate- and high-risk melanoma.
AB  - Intermediate and high risk for recurrence melanoma comprise a unique subset of
      patients with surgically treatable melanoma for whom cure is possible but relapse
      and distant metastases likely. Strategies to improve the prognosis for such
      patients with effective adjuvant therapies are critical. In recent randomized
      trials conducted by the cooperative groups in the United States of patients at
      high risk for recurrence (patients with thick primary melanomas and those with
      regional lymph node metastases) administered adjuvant therapy with high-dose
      interferon alfa-2b (HDI), relapse-free survival and overall survival rates
      improved significantly. Research efforts in this area continue to assess the role
      of intermediate-dose interferon, but there is no convincing evidence of success
      of the lower-dose regimens, despite the reduction in toxicity. For a subset of
      patients at highest risk (two or more involved lymph nodes), a regimen of therapy
      for metastatic stage IV melanoma (interleukin-2 based biochemotherapy) is being
      compared with HDI in an ongoing phase III trial. For intermediate-risk melanoma,
      no effective adjuvant therapy is available. For such patients, enrollment in
      ongoing clinical trials assessing the role of shorter courses of HDI or vaccines
      should be encouraged.

PMID- 12057068
TI  - Chronic lymphocytic leukemia.
AB  - Historically, treatment of chronic lymphocytic leukemia (CLL) essentially had
      been palliative. During the past two decades, effective new therapies for the
      treatment of CLL have emerged. The advent of fludarabine, a purine analog with
      activity against chlorambucil-resistant CLL, showed promising results with high
      response rates in previously untreated patients. These improvements in response
      and delays in disease progression have not translated into a survival benefit,
      indicating that chlorambucil may be the preferred first-line therapy when
      treatment is indicated. Allogeneic hematopoietic stem cell transplantation, by
      combining the cytoreductive effects of conditioning with a potent graft-versus
      tumor effect, is the only treatment modality with the prospect of cure for
      patients with CLL. However, conventional hematopoietic stem cell transplantation
      can be offered only to select patients with CLL because of older age and comorbid
      conditions. Novel methods of transplantation exploiting the graft-versus-leukemia
      effect while reducing the toxicity of the pretransplant conditioning are
      promising approaches that may enable more patients to benefit from this therapy.
      Monoclonal antibodies such as rituximab or alemtuzumab (Campath-1H; llex
      Pharmaceuticals, San Antonio, TX) are agents with activity in untreated and
      resistant CLL. Efforts are being focused on combining these monoclonal antibodies
      with chemotherapy and the development of rationally designed drugs.

PMID- 12057069
TI  - Newly diagnosed multiple myeloma.
AB  - Melphalan combined with prednisone (MP) has been accepted as the standard therapy
      for previously untreated multiple myeloma (MM) because most studies demonstrate
      only a modest survival benefit of combination chemotherapy regimens when compared
      with MP. There have been modest gains with more intensive myeloablative regimens
      in combination with blood stem cell support, particularly for patients with early
      primary refractory disease who subsequently achieve partial remission, and for
      the approximately 25% to 35% of patients achieving complete remission. To
      preserve the ability to adequately collect stem cells, the use of alkylating
      agents, such as melphalan, should be limited in the previously untreated patient
      with myeloma (including those older than 65 years of age) who is a candidate for
      myeloablative therapy. Pulse dexamethasone-containing regimens provide rapid
      responses and may be considered the first regimens of choice. Although
      vincristine/doxorubicin/dexamethasone (VAD) produces responses in approximately
      50% to 70% of patients with previously untreated multiple myeloma, use early in
      the disease has not improved survival. Outside of a specific study protocol, this
      regimen may be best reserved for patients with refractory (particularly
      relapsing) disease. Notable exceptions include patients with renal failure or
      plasma cell leukemia in whom the rapid responses provided by VAD may avoid
      potentially permanent, serious complications. Recently, new agents with novel
      mechanisms of action (ie, thalidomide, immunomodulatory drugs, proteosome
      inhibitors) have demonstrated activity in resistant myeloma. Because these agents
      are likely to show activity alone or in combination, newly diagnosed patients and
      previously untreated patients should be considered for clinical trials.
      Thalidomide/dexamethasone has already produced response rates of 65% to 75% in
      previously untreated patients. Its ease of administration along with stem cell
      preservation are likely to make this, followed by myeloablative therapy with stem
      cell support, the treatment of choice for untreated myeloma as confirmatory
      studies are completed.

PMID- 12057070
TI  - Heavy chain disease.
AB  - The heavy chain diseases (HCDs) are rare B-cell malignancies that are
      distinguished by the production of a monoclonal immunoglobulin heavy chain (HC)
      without an associated light chain by the malignant B-cells. There are three types
      of HCD defined by the class of immunoglobulin (Ig) HC produced: IgA (alpha-HCD),
      IgG (gamma-HCD), and IgM (mu-HCD). Alpha-HCD is the most common and occurs most
      commonly as intestinal malabsorption in a young adult from a country bordering
      the Mediterranean Sea. Treatment consists of antibiotics and improved nutrition
      and hygiene. Surgery is occasionally required for patients with bulky masses at
      risk for bowel perforation. If there is no response to antibiotics or if
      aggressive non-Hodgkin's lymphoma (NHL) is diagnosed, the patient should be
      treated with chemotherapy. Gamma- and mu-HCD are rare and essentially are found
      in patients with a B-cell NHL that produces an abnormal Ig heavy chain. These
      patients occasionally may be diagnosed with a monoclonal gammopathy of
      undetermined significance (MGUS). Patients with MGUS with NHL should be
      administered chemotherapy. Screening the serum and urine of patients with
      lymphoplasmacytoid NHL would likely identify more patients with gamma- or mu-HCD.

PMID- 12057071
TI  - Solitary bone plasmacytoma and extramedullary plasmacytoma.
AB  - Solitary bone and extramedullary plasmacytomas are rare plasma cell proliferative
      disorders. Their diagnosis is based on histologic confirmation of monoclonal
      plasma cell infiltration of a single disease site and on the exclusion of
      systemic myeloma. For both entities, the treatment of choice is localized
      radiotherapy. With modern radiotherapy and with a total dose of at least 4000
      cGy, the risk for local recurrence is less than 5%. There is no role for systemic
      chemotherapy in the management of these disorders. Approximately 30% of patients
      with solitary bone plasmacytoma (SBP) remain disease-free for several years; some
      of these patients may be cured. Patients with the best prognosis are those in
      whom the monoclonal protein disappears by 1 year after radiotherapy. The
      prognosis of patients with solitary extramedullary plasmacytoma (SEP) appears to
      be better than for patients with SBP because approximately 70% of patients with
      SEP remain disease-free at 10 years. With more sensitive staging procedures, the
      diagnosis of SBP and SEP may become less common, but the number of patients with
      prolonged stability and cure may increase.

PMID- 12057072
TI  - Primary systemic amyloidosis.
AB  - Primary amyloidosis is a plasma cell dyscrasia in which insoluble immunoglobulin
      light chain fragments are produced and polymerize into fibrils that deposit
      extracellularly, causing visceral organ dysfunction and death. The disorder is
      rare. Its recognition requires understanding the association between nephrotic
      syndrome, cardiomyopathy, peripheral neuropathy, and hepatomegaly with
      amyloidosis. The most important screening test for amyloidosis is immunofixation
      of the serum and urine to detect a monoclonal immunoglobulin light chain. All
      patients need the diagnosis confirmed histologically. The least invasive source
      of tissue for amyloid detection is the subcutaneous fat. The most important
      prognostic factor is whether there is cardiac involvement, which is best assessed
      by echocardiography with Doppler studies. Therapies used include oral
      melphalan/prednisone and high-dose corticosteroids. High-dose chemotherapy
      followed by stem cell reconstitution seems to provide the highest reported
      response rates. Transplant is associated with unique morbidities not seen in the
      transplantation of patients with other hematologic malignancies.

PMID- 12057073
TI  - Recurrent cervical cancer.
AB  - There are limited treatment options for patients with recurrent cervical
      carcinoma. Because of low response rates and a negligible impact on long-term
      survival, the use of chemotherapy in patients with unresectable recurrent disease
      should be considered palliative. Generally, radiation therapy in previously
      irradiated patients is considered palliative. For patients who develop recurrent
      disease after definitive surgery who have not received prior radiation therapy,
      salvage radiation therapy is the treatment of choice. Similarly, patients who
      have received definitive primary radiation therapy are candidates for surgical
      resection of their recurrence. However, there are specific criteria for surgical
      resection. Radical hysterectomy may be an option for the very rare patient with a
      small (<2 cm) centrally located recurrence in the cervix or vaginal fornices.
      However, for most patients, pelvic exenteration remains the only therapeutic
      option that offers the possibility of long-term survival. Patients who are
      candidates for exenteration are those with central local recurrences that have
      not extended to the pelvic sidewalls. The introduction of high-dose-rate
      intraoperative radiation therapy (HDR-IORT) combined with radical surgical
      resection has widened the scope of patients who may be offered surgery. Patients
      who in the past may not have been surgical candidates may benefit from radical
      surgical resection combined with HDR-IORT. All patients who are surgically fit
      and have undergone previous radiation therapy should be considered for surgical
      resection for centrally located recurrences. Patients whose recurrences extend
      close to the pelvic sidewalls should be referred to centers where HDR-IORT is
      available.

PMID- 12057074
TI  - Treatment of gestational trophoblastic tumors.
AB  - Gestational trophoblastic tumors (invasive mole, choriocarcinoma, and placental
      site trophoblastic tumor) should be classified according to the National Cancer
      Institute (NCI), World Health Organization (WHO), and International Federation of
      Gynecology and Obstetrics (FIGO) criteria into nonmetastatic, low-risk
      metastatic, and high-risk metastatic categories. Nonmetastatic tumors (FIGO Stage
      I) can be treated with a variety of single-agent methotrexate or actinomycin D
      protocols, resulting in cure of essentially all patients. Metastatic low-risk
      tumors (FIGO Stages II and III, WHO score < 8) should be treated with 5-day
      dosage schedules of methotrexate or actinomycin D, with cure rates approaching
      100%. Metastatic high-risk tumors (FIGO Stage IV, WHO score > 7) require
      combination chemotherapy with etoposide, methotrexate, actinomycin D,
      cyclophosphamide, and vincristine (EMA-CO) with or without adjuvant radiation
      therapy and surgery to achieve cure rates of 80% to 90%.

PMID- 12057075
TI  - Vaginal cancer.
AB  - Carcinoma of the vagina is an uncommon gynecologic cancer in the United States
      and throughout the world. Carcinoma in situ of the vagina and very early stage
      invasive carcinoma of the vagina may be treated with surgery. However, the
      standard therapeutic intervention for patients with carcinoma of the vagina is
      radiation therapy. In early stage vaginal carcinoma, radiation therapy is chosen
      for definitive treatment to preserve the anatomy and function of the vagina. In
      more advanced stages of vaginal carcinoma, radiation therapy is chosen as the
      standard treatment to avoid exenterative surgery, preserve anatomy and function,
      and to treat known or presumed lymph node metastasis. No randomized studies
      comparing irradiation alone versus irradiation and chemotherapy have been
      performed for patients with advanced carcinoma of the vagina. The standard
      therapy for patients with advanced cervical carcinoma is irradiation and
      concurrent cisplatin-based chemotherapy. Because the etiology and epidemiology of
      vaginal carcinoma appears identical to those of patients with invasive cervical
      carcinoma, patients with advanced vaginal carcinoma should be treated with
      irradiation and concurrent cisplatin-based chemotherapy.

PMID- 12057077
TI  - Recurrent vulvar cancer.
AB  - Recurrent vulvar cancer occurs in an average of 24% of cases after primary
      treatment after surgery with or without radiation. The relatively few primary
      vulvar cancers, combined with the low proportion of recurrences, has made it
      difficult to perform randomized studies to document the most appropriate
      therapeutic modalities. Most reports are small retrospective studies and
      anecdotal reviews that have emphasized the importance of surgery and have led to
      new approaches with respect to chemoradiation. Traditionally, the most accepted
      treatment of vulvar cancer has been and continues to be surgery. Recently,
      radiation and chemotherapy have been combined with very encouraging results. The
      therapeutic modality used depends on the location and extent of the recurrence.
      Most recurrences occur locally near the original resection margins or at the
      ipsilateral inguinal or pelvic lymph nodes. Lateralized local vulvar recurrences
      treated with a wide radical local excision with inguinal lymphadectomy results in
      an excellent cure rate of 70%. With a central pelvic recurrence with antecedent
      radiotherapy involving the urethra, upper vagina, and rectum, total pelvic
      exenteration is indicated in a select group of patients with curative intent.
      Radiotherapy or chemoradiation concomitantly with wide radical local excision of
      an advanced vulvar has proven successful in avoiding an exenteration, with
      improved survival and less morbidity. Prospective and retrospective studies have
      shown excellent results using radiation or chemoradiation with wide radical local
      excision in patients with locally advanced disease in whom adequate resection
      margins are difficult to achieve (with a central lesion requiring exenteration)
      or with debilitating medical conditions that preclude surgery. In these patients,
      chemoradiation has shown favorable results when used before a wide local
      resection. In patients with advanced local disease, external beam and
      interstitial radiation has been used for palliative and curative intent with
      encouraging results. Regional recurrences to the inguinal and pelvic lymph nodes
      have been shown to have a poor prognosis with a high mortality rate. We recommend
      that inguinal recurrences without prior radiation therapy undergo excision
      followed by radiotherapy with chemosensitization. In patients with previous
      radiation to the inguinal lymph nodes, we try to avoid any excisional procedures
      because of the high rate of complications. We offer these patients brachytherapy
      for palliation. With pelvic recurrences, we recommended chemoradiation as the
      treatment modality. In the subset of patients with distant metastasis,
      chemotherapy may be offered; however, few studies have been performed to advocate
      any single combination. The literature supports the use of 5-fluorouracil or
      cisplatin as single agents or in combination to have sensitivity against squamous
      cells. There are few studies revealing improvement in 5-year survival, thus these
      patients may benefit from recruitment into research protocols.

PMID- 12057076
TI  - Epithelial ovarian cancer.
AB  - Epithelial ovarian cancer is the most lethal of all gynecologic malignancies.
      Most women have advanced stage disease. Access to appropriate initial surgical
      management by a gynecologic oncologist is important because treatment and
      survival are affected by appropriate surgical staging and debulking of tumor.
      After debulking/staging surgery, chemotherapy with platinum-taxane-based regimens
      is appropriate for most patients. Patients with early stage, low-risk tumors may
      be cured with surgery alone. Interval cytoreductive surgery may be appropriate
      for patients who are initially suboptimally cytoreduced and are stable or
      responding to chemotherapy. The role of second-look surgery remains to be
      defined. Patients with recurrent or relapsed ovarian cancer are incurable. There
      are several chemotherapy agents that can achieve disease responses, which may be
      associated with palliation of tumor-related symptoms. Participation in clinical
      trials is encouraged for all patients. Novel approaches to managing minimal
      residual disease are being tested in hopes of decreasing the number of patients
      who relapse after achieving complete clinical remission.

PMID- 12057078
TI  - Management of bloody nipple discharge.
AB  - Bloody nipple discharge causes a high degree of anxiety in women because of fear
      of breast cancer. Commonly, the absence of palpable or mammographic abnormalities
      gives a false sense of security, causing delays in diagnosis. Initial evaluation
      with physical examination and mammography is useful in detecting high-risk cases.
      Bloody nipple discharge is most frequently benign. It is caused by intraductal
      papilloma, duct ectasia, and less frequently by breast cancer. Several diagnostic
      tests have been proposed to establish the cause of bloody nipple discharge.
      Galactography, ultrasound, and exfoliative cytology are useful only when
      positive, but have a high rate of false-negative results and do not preclude
      histologic diagnosis. More recently, ductal lavages in combination with cytology
      have provided promising results, but experience and long-term follow-up are
      limited. Traditional treatment is surgical excision of the involved ductal system
      from which the discharge emanates. Ductal excision has been the only reliable
      procedure in establishing a certain diagnosis and in controlling the bloody
      discharge. The early success reported with image-guided excision of papilloma and
      duct endoscopy promises a significant improvement in our diagnostic accuracy from
      minimally invasive emerging technology.

PMID- 12057079
TI  - HER2 overexpressing metastatic breast cancer.
AB  - More than 40,000 women in the United States die each year from metastatic breast
      cancer. Elucidation of HER2 and its role in malignant transformation has helped
      define a subset of aggressive breast cancer that may be relatively resistant to
      non-anthracycline-based therapies and hormonal agents, but responds to targeted
      molecular therapy. Trastuzumab, an antibody against HER2, has proven effective as
      single agent therapy in women with HER2 overexpressed metastatic breast cancer.
      Moreover, in combination with chemotherapy, trastuzumab has been shown to delay
      disease progression and improve overall survival for women with HER2-positive
      advanced breast cancer. The combination of chemotherapy and trastuzumab is
      emerging as a standard of care in women with HER2 overexpressed metastatic breast
      cancer. Several combination regimens using trastuzumab with taxanes, vinca
      alkaloids, or platinum compounds have demonstrated efficacy in first- and second
      line treatment settings. However, the development of anthracycline-based
      combinations has been limited by concerns of related cardiotoxicity. Newer multi
      agent regimens are in development. The optimal combination, duration, and
      sequence of trastuzumab therapy remain unknown in patients with HER2-positive
      metastatic disease. The role of continuing treatment after disease progression is
      also unclear. Evidence from some retrospective analyses suggest HER2-positive
      tumors are relatively resistant to tamoxifen and perhaps more responsive to
      aromatase inhibitors, although such data are inconclusive. HER2 status should not
      be used routinely for clinical decision making regarding hormonal therapy
      options. Several ongoing trials are attempting to address these and other issues
      related to HER2 testing to select the most appropriate candidates for these
      emerging therapies. While many questions remain, the treatment of HER2
      overexpressing metastatic breast cancer is rapidly evolving, and represents a new
      approach to treatment in oncology.

PMID- 12057080
TI  - Breast cancer: chest wall recurrences.
AB  - Irradiation is indicated for patients undergoing mastectomy as surgical
      management for breast cancer treatment when clinical or pathologic tumor and
      nodal features predict risk of local/regional recurrence. Such features include:
      tumor size >/= 5 cm, inadequate surgical margins; skin, facial, or skeletal
      muscle invasion; dermal lymphatic invasion; poorly differentiated tumor
      histology; four or more lymph nodes positive; gross extracapsular tumor nodal
      extension into soft tissues; and matted lymph nodes or enlarged lymph nodes > 2
      cm. Patients who were treated with irradiation after mastectomy can develop
      local/regional recurrences despite such adjuvant therapy. General management for
      chest wall and nodal recurrences is structured on the extent and volume of
      local/regional disease, the absence of distant metastases, the general health of
      the patient, and the extent of prior local/regional therapies, especially
      irradiation. Management of local/regional recurrence in the setting of no prior
      irradiation includes tumor debulking by systemic or surgical treatment followed
      by comprehensive chest wall and regional lymphatic irradiation. Doses are
      selected by tissue tolerances and volume of remaining disease. The management
      strategy for the patient with a history of irradiation parallels the
      nonirradiated patient with respect to systemic and surgical therapies to debulk
      the tumor to maximal response or no gross clinical disease. Radiation field
      design is determined by prior therapies. Doses to these fields are adjusted to
      normal tissue tolerance. Irradiation is given with a sensitizer such as
      hyperthermia or 5-fluorouracil chemotherapy. Use of radiation sensitizers can
      allow for a more meaningful biologic tumor effect when normal tissue tolerances
      prohibit delivery of standard tumor doses. Hyperthermia has been used effectively
      to promote complete tumor responses with use of irradiation in re-treatment
      cases.

PMID- 12057082
TI  - Early laryngeal cancer.
AB  - For early-stage laryngeal cancer, both surgery and radiotherapy are effective
      treatment modalities, offering a high rate of local control and cure for this
      select group of patients. The probability of obtaining local control for early
      glottic cancer is similar when comparing the results of radiation therapy,
      cordectomy, and hemilaryngectomy. Radiation therapy has been the treatment of
      choice for all previously untreated T1 and T2 vocal cord cancers at our
      institution. We currently treat most patients with irradiation and consider
      transoral laser excision for the small subset of patients with well-defined T1
      tumors that are limited to the mid-third of the cord. In this area, excision will
      not significantly diminish voice quality. Stage I and stage II supraglottic
      cancers may be treated with either radiation therapy alone or with a supraglottic
      laryngectomy with bilateral selective neck dissections (levels II-IV). In
      experienced hands, transoral laser excision also is an acceptable alternative for
      selected lesions. Overall, approximately 80% of patients at our institution are
      treated initially by irradiation.

PMID- 12057081
TI  - Approach to menopausal symptoms in women with breast cancer.
AB  - Hot flashes represent one of the most bothersome complaints in breast cancer
      survivors. In the last two decades, studies investigated several agents and
      natural compounds to treat these symptoms. Hormones such as estrogens and
      progestins remain the most beneficial treatment. However, many physicians and
      patients are reluctant to use these therapies because of the controversy
      regarding the hormonal effects on tumor growth and progression. Unfortunately,
      most natural and nonconventional remedies that have been scientifically
      investigated appear disappointing. Selective serotonin re-uptake inhibitors and
      other agents that seem to work in similar ways have been investigated over the
      last few years in Phase II and III trials. Mature results from two prospective,
      randomized, placebo-controlled trials reveal that selective serotonin re-uptake
      inhibitors are well tolerated, reduce hot flashes by 50%-60%, and improve sleep
      and libido. Selective serotonin re-uptake inhibitors should be considered as a
      first-line nonhormonal pharmacologic therapy for women with menopausal symptoms.

PMID- 12057083
TI  - Advanced larynx cancer.
AB  - Despite advances in diagnosis and treatment, the prognosis for patients with
      stage III-IV laryngeal cancer is not significantly different than it was four
      decades ago [1]. This failure to improve survival is multifactorial and is likely
      linked to controversy surrounding optimal treatment regimens for a heterogeneous
      patient and tumor population. At the root of this controversy is a lack of
      randomized controlled trials that compare different therapeutic options, personal
      and institutional treatment philosophies, and a paucity of standardized
      functional and quality-of-life outcome measures for specific treatment
      modalities. Therapeutic decision making is further complicated by the potential
      use of organ preservation approaches in some patients [2**, 3*, 4**]. Clearly,
      quality-of-life considerations are an integral part of treatment planning and a
      well-informed patient is necessary to achieve an optimal result. Philosophically,
      it is the physician's responsibility to recommend the best treatment option and
      to explain the other viable treatment strategies. It is our opinion that
      conservation laryngeal surgery represents the mainstay of treatment for patients
      with advanced laryngeal carcinomas, whose tumors have characteristics amenable to
      these approaches and who functionally can tolerate such procedures. For those
      patients who would likely require a total laryngectomy or who are not suitable
      for surgical conservation, organ preservation should be used as a primary option
      in a controlled setting.

PMID- 12057084
TI  - Nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma is usually present as locally advanced (stage III or IV)
      disease. Before 1980, the primary treatment was radiotherapy. The 5-year survival
      rate of patients with stage IVM0 across the world was less than 30%. Local,
      regional, and systemic recurrences are high in these patients and contributed to
      the poor survival. Sequential chemotherapy followed by radiotherapy (especially
      with the combination of cisplatin and 5-fluorouracil infusion for three courses)
      resulted in a 5-year survival rate of up to 55% in patients with stage IV
      disease. Concurrent single-agent cisplatin and radiotherapy improved 5-year
      survival rate to up to 55% in these patients. Total treatment with concurrent
      chemoradiotherapy followed by adjuvant cisplatin and 5-fluorouracil infusion
      resulted in 5-year survival rate of approximately 75%. Reversing the sequence of
      treatment by giving chemotherapy followed by concurrent chemoradiotherapy may
      improve the 5-year survival to up to 90%. In patients with recurrent disease or
      systemic metastases, the chances of salvage and long remission (many years) is
      approximately 15% to 20% with the use of adequate and effective chemotherapy.
      Newer agents, alone or concomitant with radiotherapy, are being evaluated in
      these patients.

PMID- 12057085
TI  - Cervical lymph node metastases from occult squamous cell carcinoma.
AB  - Depending on patient and tumor characteristics, reported 5-year actuarial
      survival rates of patients with cervical nodal metastasis from an unknown primary
      carcinoma range from 18% to 63%. Prognostic factors for survival include N-stage,
      number of nodes, grading, extracapsular extension, and performance status.
      Retrospective studies suggest that neck relapse is more common than are distant
      metastases or emergence of mucosal primary tumors. The treatment options include
      neck dissection alone, radiation alone to the neck with or without the putative
      mucosal origin, and combination unilateral neck dissection plus limited or
      comprehensive radiotherapy. Combination of nodal dissection with comprehensive
      bilateral radiotherapy yielded most favorable results in local-regional disease
      control. However, its impact on the quality of life should be recognized. Also,
      the confounding effects of patient selection for various treatment modalities on
      therapeutic outcome cannot be quantified. Retrospective single-institution
      comparisons between comprehensive and unilateral neck radiotherapy did not show
      apparent differences in outcome. A randomized trial to compare the therapeutic
      value of comprehensive versus volume-limited radiotherapy is being planned. No
      data were found to support the benefit of chemotherapy for the treatment of this
      disease.

PMID- 12057086
TI  - Hypopharyngeal carcinoma.
AB  - For more than 20 years, the policy at the University of Florida has been to treat
      patients with favorable stage T1-T2 pyriform sinus carcinoma by using radiation
      therapy alone, or with a planned neck dissection if advanced nodal disease is
      present. This approach usually leaves the patient with nearly normal swallowing
      and speech, and provides bilateral coverage of the regional neck and
      retropharyngeal lymphatics. More advanced lesions often are not controlled with
      radiation alone and are usually considered for partial or total
      laryngopharyngectomy if the patient is medically operable. Radiation is usually
      administered postoperatively in this setting, unless the neck disease is thought
      to be unresectable, in which case preoperative radiation is given. Recent data
      have shown that adjuvant chemotherapy administered concomitantly with
      radiotherapy results in improved cure rates for patients with advanced disease
      compared with irradiation alone. Time-honored established guidelines are still
      used, although the edges have become blurred. Therefore, patients with larger
      primary tumors now may be considered for organ preservation treatment with
      irradiation and chemotherapy, reserving surgery for salvage situations. The
      subset of patients with advanced T4 pyriform sinus cancers (in whom cure with
      chemoradiation would likely result in tracheostomy and/or gastrostomy dependence)
      may be better served with elective surgery and postoperative irradiation. The
      definition of this subset of patients is unclear but probably includes patients
      with significant cartilage destruction and those who require pretreatment
      tracheostomy. The policy at the University of Florida is to treat essentially all
      pharyngeal wall cancers with external-beam irradiation alone.

PMID- 12057087
TI  - Non-small-cell lung cancer progression after first-line chemotherapy.
AB  - Platinum-based chemotherapy is the cornerstone of care for patients with
      metastatic non-small-cell lung cancer (NSCLC). It provides symptom relief,
      improved quality of life, and prolongation of life, compared with supportive care
      alone. However, all patients with stage IV disease inevitably develop resistance
      to chemotherapy and progressive disease. Many of these patients continue to have
      acceptable performance status and would therefore be eligible for second-line or
      even third-line treatments. Unfortunately, despite an increasing number of
      chemotherapeutic agents (which are effective in chemo-naive NSCLC), very few have
      been shown to have reproducible activity in the second-line setting.
      Nevertheless, recent randomized clinical trials have demonstrated that single
      agent docetaxel improves survival and quality of life when delivered as second
      line therapy, resulting in FDA-approval for this indication. Phase II studies
      evaluating other new agents, delivered singly or in combination, also have
      reported that gemcitabine, weekly paclitaxel, and the epidermal growth factor
      receptor (EGFR) inhibitors are active in a subset of patients who progress after
      first-line platinum-based therapy. Clinical trials are imperative in identifying
      additional new agents and approaches that may improve outcomes in this disease.
      In view of the recently established role of docetaxel, ongoing randomized studies
      are using a common design of single-agent docetaxel versus docetaxel plus a novel
      investigational agent.

PMID- 12057088
TI  - Local complications of non-small-cell lung cancer.
AB  - Because of the stage-specific treatment of lung cancer, significant strides have
      been made in the treatment strategies for patients with non-small-cell carcinoma.
      Unfortunately, despite aggressive therapy, most patients will die within 5 years
      of diagnosis. Although the predominant cause of death will be secondary to the
      systemic nature of the cancer, most patients also will suffer significant
      decrements in their quality of life and functional status secondary to local
      complications. Addressing and treating the local complications of lung cancer
      aggressively may directly and immediately improve the quality of life and
      functional status of patients with extensive lung cancer. Improvements in the
      treatment of local complications of lung cancer that lead to improved performance
      status also may have an impact on the long-term survival of these patients.

PMID- 12057089
TI  - Follow-up of local (stage I and stage II) non-small-cell lung cancer after
      surgical resection.
AB  - Non-small-cell lung cancer (NSCLC) is responsible for more deaths each year in
      the United States than is any other malignancy. Early stage disease can be cured
      with surgical resection. Postoperative surveillance for recurrent disease and the
      development of second malignancies are important parts of the overall treatment
      plan. Follow-up strategies have been analyzed and guidelines (most notably those
      of the National Comprehensive Cancer Network ) have been published. However,
      common practice often does not comply with these rationally developed guidelines.
      Understanding the general principles of effective surveillance may improve
      compliance with the guidelines and may lead to more cost-effective management.
      New methods of surveillance, postoperative risk stratification, and emerging
      therapies may alter these recommendations for postoperative surveillance of
      patients with early stage NSCLC in the future.

PMID- 12057090
TI  - Inoperable localized stage I and stage II non-small-cell lung cancer.
AB  - Early stage, medically inoperable non-small-cell lung cancer is a treatable
      disease. A thorough clinical work-up is necessary to optimize management for this
      group of patients. Thoracic radiation therapy has been used for such patients
      with achievement of durable local control and prolonged survival. To improve upon
      the results of standard fractionation radiation therapy, novel approaches are
      needed. Dose escalation may further enhance local tumor control and survival
      rates. Efforts to minimize irradiation to normal lung parenchyma are necessary.
      Multiple strategies to optimize the therapeutic ratio are being investigated.
      Elimination of elective nodal irradiation may reduce late toxicity of treatment
      but may compromise locoregional control. Other strategies, such as intensity
      modulated radiation therapy with dose volume histograms will help minimize lung
      parenchyma irradiation, which will reduce the probability of radiation
      pneumonitis. Chemotherapy appears to play a minimal role in the treatment of
      inoperable limited disease, but researchers continue to conduct investigational
      trials with active chemotherapeutic agents in the hopes of reducing local and
      distant tumor failures.

PMID- 12057091
TI  - Elderly patients with lung cancer: biases and evidence.
AB  - Although 60% of those diagnosed with non-small-cell lung cancer are 60 years of
      age or older, the elderly are often undertreated. Furthermore, those older than
      age 70 are under-represented in clinical research trials. Tremendous bias exists
      against treating the elderly; therapeutic nihilism and constrained
      societal/financial resources conspire to maintain the status quo. In limited
      stage small cell carcinoma of the lung (SCLC), a pivotal meta-analysis by Pignon
      et al. showed no obvious benefit for chemoradiation over chemotherapy alone in
      patients older than 70 years of age. However, more recent trials have revealed a
      clear-cut benefit for fit elderly patients to receive combined modality therapy
      versus chemotherapy alone, even though outcome generally remains superior for
      younger patients. For patients with locally advanced non-small-cell lung cancer,
      conflicting results exist. Individual trials evaluating combined modality therapy
      have shown no impairment in survival for older patients, but retrospective
      analyses of the Radiation Therapy Oncology Group database have demonstrated that
      increased therapeutic intensity does not translate into improved outcome compared
      with standard, single daily fraction radiation alone. Weighted survival analyses
      that deduct time spent with progressive disease or significant toxicity have
      reinforced this notion. In advanced non-small-cell lung cancer, fit elderly
      patients who receive platinum-based regimens do as well, or nearly as well, as
      patients younger than age 70, although the incidence of neutropenia and fatigue
      is often higher. Platinum doses above 75 mg/m2 every 3 weeks to 4 weeks are
      relatively more toxic in the elderly than are lower doses. Three separate studies
      from Italy have formally assessed the elderly. One showed superiority for single
      agent vinorelbine versus best supportive care regarding survival rates and
      quality of life. A second showed a marked survival advantage for combination
      vinorelbine and gemcitabine versus vinorelbine alone. However, a much larger,
      more credible study demonstrated no benefit for combination vinorelbine and
      gemcitabine versus the constituent single agents. To date, no elderly-specific
      trials have addressed the role of taxanes or of platinum-based combination
      therapy versus non-platinum monotherapy or doublets. Comprehensive evaluation of
      comorbidities and their influence on outcome have not been conducted, and there
      are virtually no data for patients older than age 80.

PMID- 12057092
TI  - Metastatic colorectal cancer.
AB  - Despite advances in screening procedures and the use of adjuvant therapy,
      approximately 50% of patients with colorectal cancer eventually will develop
      metastatic disease. Long-term disease-free survival can be achieved in 25% to 40%
      of selected patients who undergo resection of liver or lung metastases. For all
      other patients, treatment is palliative. For decades, 5-fluorouracil was the only
      available drug for colorectal cancer; hence, numerous trials were performed that
      used various administration schedules and modulating agents to improve
      therapeutic efficacy. The addition of leucovorin to 5-FU improves response but
      not survival. Infusion schedules alter the toxicity profile but have a negligible
      impact on survival. Irinotecan was the first new drug to demonstrate activity in
      colorectal cancer. It was used initially in the second-line setting, where it was
      shown to improve quality of life and survival over best supportive care or
      infusional 5-FU. Recently, irinotecan has been incorporated into the front-line
      treatment of metastatic colorectal cancer in combination with 5-FU and
      leucovorin; this combination improves survival by approximately 3 months. Careful
      patient selection and adherence to strict dose adjustments are essential to
      prevent significant toxicity when patients are treated on this regimen. The oral
      fluoropyrimidine capecitabine recently has been approved for the front-line
      treatment of patients with colorectal cancer who are not appropriate candidates
      for combination therapy. Oxaliplatin, a novel DACH (diaminocyclohexane) platinum
      with definite activity in colorectal cancer, is approved for this disease in
      Europe and is undergoing phase III clinical trials in the United States. Other
      drugs with potential activity in colorectal cancer include raltitrexed,
      pemetrexed disodium, and the epothilone analog BMS-247550 (Bristol-Myers Squibb,
      New York, NY). Novel cytostatics with promising activity in colorectal cancer are
      being evaluated in clinical trials, including epidermal growth factor receptor
      inhibitors, such as IMC-C225 (Imclone Systems, New York, NY) and ZD1839
      (AstraZeneca, London, UK), angiogenesis inhibitors such as bevacizumab and SU5416
      (Sugen, San Francisco, CA), and vaccines such as CEAVac (Titan Pharmaceuticals,
      San Francisco, CA). For those patients whose disease is localized to the liver,
      there also is an emerging role for local therapies, including cryosurgery,
      radiofrequency ablation, and hepatic artery infusional chemotherapy, and
      resection. The emergence of these new drugs and new interventional modalities has
      allowed physicians who treat colorectal cancer to move beyond 5-FU.

PMID- 12057094
TI  - Gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) are mesenchymal gut tumors that differ
      dramatically from other histologically similar neoplasms, such as leimomyomas,
      leiomyosarcomas (LMS), and neural tumors. Complete surgical removal remains the
      best current therapy for GISTs, but even major resections are associated with
      recurrence in approximately 90% of cases. GISTs are remarkably resistant to
      irradiation and standard chemotherapy; there is no role for treatment with those
      modalities. Treatment of advanced GIST patients with STI571, a novel selective
      tyrosine kinase inhibitor, results in remission rates that approach 60% and
      overall tumor control rates of 85%. Selected groups of patients, as based on
      tumor mutational status, have response rates as high as 80%. To date, STI571
      therapy remains the only systemic treatment for GISTs to have meaningful clinical
      activity. Though other molecularly targeted therapies exist in oncology (eg,
      trastuzumab), STI571 is one of the first that applies a drug specifically
      designed to inhibit the product of a constitutively-activating mutation that
      drives pathogenesis of a solid tumor. Its use can serve as a paradigm for
      designing molecularly targeted therapies for other malignancies.

PMID- 12057093
TI  - Hepatitis C and hepatocellular carcinoma.
AB  - Chronic hepatitis C infection (HCV) accounts for approximately 50% of the cases
      of hepatocellular carcinoma (HCC) in the United States. Cirrhosis or an advanced
      stage of fibrosis is the major risk factor of HCC; patients with cirrhosis are
      recommended to undergo surveillance with alpha-fetoprotein and ultrasound. Alpha
      interferon (IFN-alpha) is associated with a reduced risk of HCC in patients with
      chronic infection but insufficient data exist to recommend treatment of patients
      with cirrhosis and HCV for this reason alone. Resection and liver transplantation
      are the only "curative" therapies available. Advanced fibrosis or cirrhosis in
      patients with HCC limits the number of patients for whom resection is applicable.
      Moreover, the remaining liver is at high risk of developing a second primary
      tumor. Partial hepatic resection for hepatocellular carcinoma should be
      restricted to patients with well-compensated cirrhosis (Child's A class).
      Acceptable parameters include a single lesion not exceeding 5 cm, normal levels
      of bilirubin, and absence of portal hypertension. Liver transplantation is the
      best definitive treatment for HCV-infected patients who have small, localized HCC
      (solitary lesion not greater than 5 cm, or no more than 3 lesions, none of which
      are greater than 3 cm). Limitations of liver transplantation as a therapy for HCC
      are the scarcity of donor organs and the prolonged waiting time during which
      continued tumor growth occurs. Living donors can reduce waiting time and increase
      the number of patients treatable by transplantation. Chemoembolization and local
      ablation therapies have not been shown to confer survival benefits as primary
      treatments for HCC. The potential benefit of these procedures in controlling
      tumor growth to "bridge" patients to liver transplantation must be further
      investigated. Similarly, systemic chemotherapy and hormonal therapy do not
      generally produce a survival advantage. However, recent studies that used
      octreotide and combination doxorubicin/cisplatin/5-FU/interferon appear to be
      promising.

PMID- 12057095
TI  - Low-grade gliomas.
AB  - Low-grade gliomas are uncommon primary brain tumors classified as histologic
      grades I or II in the World Health Organization (WHO) classification. The most
      common variants are pilocytic and low-grade astrocytomas, oligodendrogliomas, and
      mixed oligo-astrocytomas located in the cerebral hemispheres. Prognostic factors
      that predict progression-free and overall survival include young age, pilocytic
      histology, good Karnofsky performance status, gross total resection, lack of
      enhancement on imaging, and small preoperative tumor volumes. Edema and vasogenic
      effects are typically managed with corticosteroids. Dexamethasone is given at an
      initial dosage of 4 mg given four times daily. Anticonvulsants are given
      prophylactically after resection and for patients who present with seizures. The
      rationale for open craniotomy depends on the need for immediate palliation of
      symptoms by reduction of intracranial pressure or focal mass effect, and/or
      improved oncologic control. Gross total resection of tumor is generally defined
      as the absence of residual enhancement on contrast-enhanced postoperative MRI
      scan. Most retrospective studies suggest that patients who have undergone a gross
      total resection of tumor have improved survival. Depending upon the proximity of
      the tumor to eloquent brain, gross total resection may or may not be possible. In
      these cases a stereotactic biopsy is required to provide the histologic
      diagnosis. Adjuvant radiotherapy is recommended for patients with incompletely
      resected grade II tumors or for patients older than age 40 regardless of extent
      of resection. It may be considered for any pilocytic astrocytoma from which a
      biopsy has been performed. Phase III randomized prospective trials have shown
      statistically significantly improved progression-free survival at 5 years with
      the addition of radiotherapy, though overall survival does not appear different.
      Based on prospective randomized phase III trials, 50.4 Gy to 54 Gy of
      conventionally fractionated radiotherapy appears to be a safe and effective
      regimen with minimal neurotoxicity; 45 Gy may be adequate for biopsied pilocytic
      astrocytomas. Currently, RTOG trial 98-02 is investigating the efficacy of
      postradiation PCV chemotherapy (procarbazine, CCNU, and vincristine) in the
      treatment of newly diagnosed unfavorable low-grade gliomas. Other areas of
      investigation include Temozolomide chemotherapy and the association of 1p and 19q
      chromosomal deletions with prolonged survival in oligodendrogliomas and
      sensitivity to PCV chemotherapy. Radiosurgery and/or experimental chemotherapy
      may provide some measure of local control in the recurrent disease setting.

PMID- 12057096
TI  - Adults with newly diagnosed high-grade gliomas.
AB  - Despite tremendous advances in brain tumor molecular biology and several emerging
      novel therapies, multimodality therapy that includes surgery, radiation therapy
      (RT), and chemotherapy is still the cornerstone of high-grade glioma treatment.
      The first step in high-grade glioma therapy is surgery and a maximal resection
      should be attempted to reduce the tumor burden before initiation of other
      adjuvant therapies. External beam radiation therapy (EBRT) generally follows
      surgery, using conventional dosage, and fractionation, and ideally a three
      dimensional conformal technique. Stereotactic radiosurgery (SRS) to maximize
      cytoreduction may be used in selected cases. Because no curative chemotherapy
      exists for high-grade glioma, we always consider an investigational agent either
      before or concurrently with RT. However, the use of a standard cytotoxic agent,
      such as temozolomide alone or combined with 13-cis-retinoic acid also is a
      rational choice particularly for patients with relatively good prognostic factors
      for whom an investigational agent would not be available. The management of
      anaplastic oligodendroglioma does not differ significantly from other high-grade
      gliomas in terms of surgery, RT, or investigational or protocol agent; however,
      these tumors appear to respond to chemotherapy that includes a combination of
      procarbazine, CCNU, and vincristine (PCV) [1**]. The vincristine provides more
      toxicity than benefit and it is our practice to only use a combination of
      procarbazine and CCNU (PC). A single agent, such as temozolomide is an
      increasingly used and rational choice for anaplastic oligodendroglioma. It is our
      belief that early, aggressive multimodality treatment still provides the best
      chance for long-term control of high-grade gliomas, particularly in patients with
      good prognostic factors. However, despite best therapy and state-of-the-art
      technology, most patients with high-grade glioma will experience progression or
      recurrence and will require either a change in the ongoing therapeutic strategy
      or additional treatment. Better therapies are necessary and progress will only be
      made through investigation of promising agents in well-designed clinical trials.

PMID- 12057097
TI  - Neoplastic meningitis.
AB  - Neoplastic meningitis is recognized clinically in 4% to 7% of patients with
      extraneural cancer, but it remains dramatically under-diagnosed. The frequency of
      neoplastic meningitis is increasing because of heightened clinical suspicion,
      improved neuroimaging techniques, and longer survival in patients with
      extraneural cancer Longer survival allows residual tumor cells within central
      nervous system sanctuary sites time to become symptomatic. Affected patients may
      present with cerebral, cranial nerve, or spinal signs and symptoms, depending on
      the specific sites of central nervous system (CNS) involvement. Magnetic
      Resonance Imaging (MRI) seems to be sensitive for detecting metastatic deposits
      along the neuraxis. However, metastases at a microscopic level are below the
      resolution of MRI scanning. As a result, the standard diagnostic test for
      neoplastic meningitis remains the cytologic identification of malignant cells in
      cerebrospinal fluid (CSF). Although CSF cytology is useful, malignant cells are
      not detected in as many as one third of patients who have compelling clinical or
      radiographic evidence of neoplastic meningitis. Novel assays are being tested
      that may enhance the early identification of malignant cells in CSF. Currently,
      the diagnosis occurs generally after the onset of neurologic manifestations and
      heralds a rapidly fatal course for most patients. By the time symptoms appear,
      most tumors have disseminated widely within the CNS, due to cortical irritation,
      compression of nervous system structures, or obstruction of CSF flow. At this
      stage surgery, cranial irradiation, and chemotherapy are rarely, if ever,
      curative. The goals of treatment are to improve or to stabilize the neurologic
      status of patients and to prolong survival. A major problem in treating
      neoplastic meningitis is that the entire neuraxis must be treated. If only
      symptomatic areas are treated, reseeding of the neuraxis with tumor cells will
      occur. Therefore, intrathecal chemotherapy remains a mainstay of therapy.
      Currently, four therapeutic agents are available for intrathecal treatment:
      methotrexate, ara-C, sustained-release ara-C (DepoCyt; Chiron Therapeutics, San
      Francisco, CA), and thiotepa. Unfortunately, intrathecal chemotherapy does not
      treat bulky disease in the subarachnoid space, and often is slow to stabilize
      progressive neurologic deficits. For these reasons, radiation therapy to sites of
      symptomatic disease and sites of bulky disease on imaging studies is recommended.
      High dose intravenous methotrexate may be as effective as intrathecal
      methotrexate. Alternative approaches (which offer less toxicity, enhanced
      therapeutic effect, and prolonged survival) are being investigated.

PMID- 12057098
TI  - Pediatric glial tumors.
AB  - Glial neoplasms in children comprise many heterogeneous tumors that include
      pilocytic and fibrillary astrocytomas, ependymomas, and the diffuse intrinsic
      pontine gliomas. In contrast to adults, most of whom present with high-grade
      fibrillary neoplasms, alternate histologies represent most cases seen in the
      pediatric setting. In addition, although most adult gliomas are supratentorial in
      location, in pediatrics infratentorial tumors (posterior fossa and brain stem)
      predominate. We discuss three specific tumors: diffuse intrinsic pontine gliomas;
      pilocytic astrocytomas; and ependymomas. Maximal surgical resection is the
      mainstay of therapy for both pilocytic astrocytomas and ependymomas. Failure to
      achieve an optimal resection often results in progression and the need for
      further therapy for patients with pilocytic astrocytomas, and is ultimately fatal
      in most children with subtotally resected ependymomas. Surgical resection has no
      role in the treatment of pontine gliomas. Focal radiation therapy is included
      routinely in the treatment of ependymomas, and it has been shown to improve event
      free survival. This therapy also is used in the treatment of pontine gliomas
      because radiation treatment appears to slow inevitable tumor progression.
      Radiation therapy in pilocytic astrocytomas is generally reserved for patients
      who progress after an initial surgical resection or for those patients with
      midline tumors; these patients are poor candidates for aggressive surgical
      resection. The role of chemotherapy in these tumors is in evolution. Chemotherapy
      for pilocytic astrocytomas, particularly in young children (for whom radiation
      therapy is avoided), appears to be effective in the treatment of a subset of
      patients. Up-front chemotherapy is generally reserved for the youngest children
      who present with ependymoma. In the recurrence setting, chemotherapy has shown
      some activity, although this approach is never curative. Despite the application
      of various chemotherapeutics and other biologic agents, none of these therapies
      has improved the prognosis for patients with the uniformly lethal pontine glioma.

PMID- 12057099
TI  - Brain metastases.
AB  - Metastatic tumors to the brain are an increasing cause of morbidity and mortality
      in patients with systemic cancers. Many new therapies used to treat systemic
      cancers do not penetrate the central nervous system (CNS) and do not protect
      patients from the development of brain metastases. Surgery, radiosurgery, and
      radiation therapy are all used to treat brain metastases. It is in our opinion a
      mistake to use only one or two of these modalities to the exclusion of other(s).
      The role of systemic chemotherapy is still limited, due to both the issues of
      drug delivery caused by the blood brain barrier and to the relative resistance of
      many of these tumors to chemotherapy. Traditionally, brain metastases have been
      grouped together regardless of the origin of the tumor and have been treated with
      a single algorithm. As we encounter more patients for whom treatment of the brain
      metastases is an important determinant of survival, we must tailor our treatment
      strategies to individual tumor types. Also, we must recognize differences in each
      tumor's sensitivity to chemotherapy and radiotherapy and differences in their
      biology.

PMID- 12057100
TI  - Photodynamic therapy for mesothelioma.
AB  - Multiple trials of traditional cancer therapies for malignant pleural
      mesothelioma (including surgery, radiation therapy, and chemotherapy) have not
      convincingly demonstrated that any one treatment is superior to supportive care
      alone. Although there have been reports of long-term survivors who were treated
      with aggressive surgery combined with radiation and aggressive multi-agent
      chemotherapeutic regimens, these patient populations are highly selected and
      results cannot be generalized to a larger population. Despite attempts to use
      aggressive multimodality therapies, disease recurs in most patients. Local
      failure in particular is a large part of the natural history of mesothelioma,
      especially after surgery alone. Therefore, one of the major considerations in the
      development of new treatments is the inclusion of aggressive local therapies.
      Photodynamic therapy (PDT), a local treatment modality, is being evaluated as an
      adjuvant therapy to surgical resection. Clinical use of PDT requires the use of a
      photosensitizing agent and light of a wavelength specific to the absorption
      characteristics of the sensitizer in the presence of oxygen. The treatment effect
      of PDT is superficial, mostly because of the limited depth of light absorption in
      tissues. Therefore, it is theoretically an ideal treatment for tissue surfaces
      and body cavities after surgical debulking procedures. One theoretical advantage
      of PDT is that it can be used to treat the lung surface after a pleurectomy;
      therefore, patients may be treated with a pleurectomy rather than with an
      extrapleural pneumonectomy. Several studies have evaluated the efficacy of PDT in
      the treatment of mesothelioma. Clinical studies have not proven convincingly that
      the use of PDT is superior to the use of other adjuvant therapies or to surgery
      alone. The advent of newer photosensitizers and improved laser technology has led
      to a renewed interest in evaluating PDT. Additional studies are necessary to
      determine the role of PDT in the treatment of mesothelioma.

PMID- 12057102
TI  - Malignant peritoneal mesothelioma.
AB  - This paper summarizes the author's thoughts about the use of cytoreductive
      surgery combined with intraperitoneal hyperthermic chemotherapy (CS-IPHC) for
      treatment of peritoneal malignant mesothelioma. Pleural malignant mesotheliomas
      are by far more common (about ten- to thirty-fold) than the peritoneal variants
      (2.2 cases per 1 million in the US). Other locations (pericardium, tunica
      vaginalis) are very rare. It is well known that chemotherapy for mesothelioma is
      largely unsatisfactory, and measurement of treatment responses can be difficult.
      Single agent responses are all less than 20% with currently available agents for
      systemically administered drugs. Multiple drug combinations are typically more
      toxic, and have yielded little consistent demonstrable benefit with major studies
      reporting median survivals consistently under a year. There is currently more
      attention being paid to the response category of "stable" or absence of disease
      progression in concert with quality of life measurements; all regimens show poor
      durability. With peritoneal malignant mesothelioma, malignant ascites is a common
      presentation and a major factor in disease-related morbidity and mortality.
      Interperitoneal administration of agents is attractive, but drug distribution is
      an issue, as are response rates and durability. Multiple treatments are required;
      further, all neoplasms with peritoneal dissemination are typically understaged by
      current radiologic tests (CT, MRI), and the variable uptake of sugar by the small
      bowel limits the use of positron-emission tomography (PET) imaging for peritoneal
      malignant mesothelioma. Also, symptoms of bowel obstruction are not uncommon, and
      any mechanical component of obstruction will not improve with any form of
      chemotherapy. The author's approach relies on surgery to achieve the following:
      1) accurate staging; 2) tumor debulking, as possible, and treatment of mechanical
      obstruction as well as prevention of impending obstruction by resection or
      bypass; and 3) preparation for the use of intra-operative hyperthermic
      chemotherapy perfusion. This approach has been associated with rapid clinical
      symptom improvement, as well as a reliable and durable resolution of ascites with
      a single therapy. Morbidity and mortality have been acceptable with about 27
      month median survival. The inability to provide effective systemic therapy to
      maintain or consolidate these gains is problematic.

PMID- 12057101
TI  - Intracavitary therapies for mesothelioma.
AB  - The diagnosis of mesothelioma needs to be defined histologically. The staging
      system has been recently redefined anatomically, but may not be applicable to
      extrapleural mesothelioma. Further clinicopathologic studies need to be performed
      to molecularly classify the disease further, according to prognosis.
      Intracavitary therapy has a definite role in the treatment of mesothelioma.
      Randomized studies of intracavitary therapies are needed to define the best
      treatment option. The role of complementary therapeutic modalities such as
      surgery and radiotherapy needs to be defined by randomized studies. There is an
      urgent need to better understand the biology of mesothelioma, which may lead to
      more focus on molecularly relevant therapies.

PMID- 12057103
TI  - Locally advanced prostate cancer.
AB  - Standard therapy for clinically localized prostate cancer includes radical
      prostatectomy, external beam radiotherapy, or transperineal interstitial
      brachytherapy. Patients eligible for standard therapy are those with low risk
      features as defined by various risk group classifications, which generally
      include clinical stage T1 or T2a, serum prostate-specific antigen (PSA) less than
      10 ng/mL, and biopsy Gleason sum of 6 or less. Although there has been important
      evolution in the performance of these techniques, particularly with respect to
      functional outcomes, these approaches for low-risk disease are relatively mature,
      and the cure rates with each of these therapies are similar in this patient
      population; locally advanced disease is more difficult to cure, however.
      Biochemical disease-free survival rates in men undergoing radical prostatectomy
      are clearly related to the pathologic stage. Prognostic groups can be defined
      based on pathologic stage with increasingly worse outcomes based on extracapsular
      extension (ECE), margin status, and the status of the lymph nodes and seminal
      vesicles. In patients with low risk features, the positive margin rate is
      generally low, making the presence or absence of ECE the dominant variable in
      predicting the likelihood of treatment failure. These observations suggest that
      more aggressive therapy is needed to cure those who are likely to have ECE or
      other adverse histologic features. Several nomograms predicting the likelihood of
      ECE or 5-year biochemical failure rates are now in routine clinical use, and can
      be used to select men at high risk of failure with single modality therapy for
      more aggressive treatment strategies. However, the optimal form of aggressive
      therapy for these patients is unknown.

PMID- 12057104
TI  - Early-stage testis cancer.
AB  - The treatment of low-stage testis cancer (defined as clinical stage I or low
      volume clinical stage II disease) varies, depending on whether or not the
      orchiectomy specimen reveals seminoma or nonseminoma. Treatments for clinical
      stage I seminoma include radiotherapy to the retroperitoneum, surveillance, or
      two courses of carboplatin chemotherapy. Until the results of an ongoing
      randomized study comparing radiotherapy with two courses of carboplatin are
      known, standard accepted treatments currently include radiotherapy or
      surveillance. In nonbulky clinical stage II seminoma, therapeutic options include
      radiotherapy or cisplatin-based chemotherapy. For clinical stage I nonseminoma,
      equivalent short-term survival rates are obtained with either nerve-sparing
      retroperitoneal lymph node dissection (RPLND), surveillance, or two courses of
      BEP (bleomycin, etoposide, and platinum) chemotherapy. However, minimization of
      toxicity of treatment would argue that the two preferred treatments in clinical
      stage I nonseminoma are nerve-sparing RPLND or surveillance. For low- volume
      clinical stage II nonseminoma, options include three courses of BEP or primary
      RPLND. The overall chance for cure is essentially the same for either of these
      options. Therefore, in each clinical stage of early-stage testis cancer,
      therapeutic options exist that, based upon current data, are therapeutically
      equivalent in the short term. Therefore, the ultimate choice of therapy is also
      dependent upon the short- and long-term toxicity of therapy and the likelihood of
      late recurrence of disease.

PMID- 12057105
TI  - Advanced testis cancer.
AB  - Advanced testis tumors are highly curable. The treatment strategy is chemotherapy
      followed by the surgical exeresis of residual disease. The standard chemotherapy
      regimen is BEP (bleomycin, etoposide, and cisplatin); the number of cycles of
      chemotherapy depends upon prognostic factors, based on the primary site,
      histology, presence of visceral metastases, and serum tumor marker levels.
      Patients in the good-risk group receive three cycles of chemotherapy, whereas
      those in the intermediate- and high-risk groups receive four cycles. Exeresis of
      all residual disease and systematic postchemotherapy retroperitoneal dissection
      in bulky disease are mandatory. When complete exeresis of necrotic tissue,
      teratoma, or active germ-cell cancer has been performed, no further postsurgical
      treatment is warranted. A multidisciplinary approach, rigorous administration of
      chemotherapy, and skill in surgery of germ-cell tumors are favored in the
      treatment of these patients in trained centers.

PMID- 12057106
TI  - Locally advanced and metastatic bladder cancer.
AB  - Metastatic transitional cell carcinoma of the bladder is an aggressive neoplasm
      characterized by rapid growth and dissemination with a median survival of
      typically less than 1 year. Despite the availability of a myriad of
      antineoplastics with moderate-significant anti-tumor activity yielding overall
      response rates in the 40% to 80% range, randomized trials continue to demonstrate
      median survival rates in the 13- to14-month range, with very limited long-term
      survival. Subsets of patients with advanced bladder cancer present additional
      management problems, including those with renal insufficiency or nontransitional
      cell histology. Various observers have noted the similarity in treatment outcomes
      in advanced bladder cancer and extensive small cell lung cancer where
      chemotherapy produces relatively high response rates but with limited impact on
      survival. The optimal chemotherapy combination for patients with advanced bladder
      cancer remains undefined, however, there is increasing recognition that in order
      to achieve tangible improvements in complete response rates and survival in this
      disease will likely require a combination of chemotherapy and targeted molecular
      therapies and in some settings adjunctive surgery.

PMID- 12057107
TI  - Advanced renal cell carcinoma.
AB  - Advanced renal cell carcinoma (RCC) is a disease that is highly resistant to
      systemic therapy and is difficult to treat. Nephrectomy should be seriously
      considered in patients who present with metastatic disease prior to systemic
      therapy, and surgery remains a reasonable option in patients who present with
      resectable metastases. Numerous studies with many different treatment modalities,
      including chemotherapy, immunotherapy, and radiation therapy, have failed to
      consistently benefit patients, with no single agent or combination therapy
      showing a reproducible response proportion of 20% or higher. Interleukin-2 (IL-2)
      and interferon-alfa (IFN alfa)-based therapies remain the most commonly used
      agents to treat patients with advanced disease, demonstrating low but
      reproducible response proportions in the 10% to 20% range, with durable responses
      of 5% or less. Recent randomized studies demonstrate a survival advantage for
      patients receiving systemic IFN-based therapy, but this advantage is marginal.
      Novel treatment strategies are being investigated, with some encouraging early
      results using vaccines and allogeneic bone marrow transplant. The identification
      of new agents with more effective antitumor activity is a high priority in the
      treatment of advanced RCC.

PMID- 12057108
TI  - Localized renal cell carcinoma.
AB  - The last decade has brought dramatic changes in our understanding of localized
      renal tumors. Due to vast improvements in the abdominal imaging modalities of
      computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI),
      approximately two-thirds of patients at our center have their renal tumors
      discovered incidentally. This tumor stage and size migration has vastly improved
      survival rates; more than 75% of patients with localized renal tumors achieve
      cure after surgical resection. In addition, the increased presentation of small,
      incidental tumors has increased the therapeutic options for urologic surgeons
      with surgical or tumor ablative techniques who now consider preservation of renal
      function as a goal equally important to local tumor control. Renal cortical
      tumors, viewed previously as a single type of cancer (ie, hypernephroma, renal
      cell carcinoma) with a uniform metastatic potential, are far more complex in
      nature. Renal cortical tumors are a family of neoplasms with distinct
      histological subtypes and distinct cytogenetic and molecular defects. Metastatic
      potential, once thought to be dependent only on tumor size, grade, and stage,
      varies according to tumor histologic subtype, ranging from the most potentially
      malignant conventional clear cell carcinoma, to the indolent papillary and
      chromophobe carcinomas, to the virtually benign renal oncocytoma. Surgical
      approaches to the localized renal cortical tumors now include the classic radical
      nephrectomy, kidney-sparing surgery, and innovative techniques that involve
      laparoscopy. New therapeutic modalities, such as renal cryosurgery and
      radiofrequency ablation, are under active investigation. Whether these new
      approaches to localized renal tumors will supplement or replace current surgical
      techniques will depend on the findings of carefully designed and controlled
      clinical trials.

PMID- 12057110
TI  - Organ transplant-related lymphoma.
AB  - Post-transplant lymphoproliferative disorder is a curable disease in which a wide
      range of treatment strategies has met with a degree of success. Both the disease
      and the organ transplant setting in which it occurs are highly variable. A
      sequential approach to treatment is preferred, starting with reduction in
      immunosuppressives. Rituximab or interferon alfa can be tried next, in the hope
      of avoiding chemotherapy. Rituximab has significant activity and has shown no
      additional toxicities in transplant recipients. It may be appropriate to add
      rituximab to the initial treatment in critically ill patients. Cytotoxic
      chemotherapy is effective but significantly more toxic in this patient
      population. Effective therapy should be instituted before progressive disease
      results in declining performance status and multi-organ dysfunction. The goal of
      treatment is complete and durable remission. Adoptive T-cell therapy is an
      effective and promising alternative for allogeneic bone marrow transplant
      recipients.

PMID- 12057109
TI  - Human T-cell lymphotropic-I-associated leukemia/lymphoma.
AB  - Human T-cell lymphotropic virus-I (HTLV-I)-related adult T-cell leukemia/lymphoma
      (ATL) is a model disease for proof of viral oncogenesis. HTLV-I infection is
      endemic in southern Japan and the Caribbean basin, and occurs sporadically in
      Africa, Central and South America, the Middle East, and the southeastern United
      States. ATL occurs in only 2% to 4% of HTLV-I-infected people [1-3]. When it does
      occur, it is usually aggressive and difficult to treat; most people survive for
      less than 1 year [1-3]. Combination chemotherapy with cytotoxic agents has
      yielded complete response rates of 20% to 45%, but responses usually last only a
      few months [3]. Recently, novel treatments, such as monoclonal antibodies
      directed at the interleukin-2 receptor and the combination of interferon alfa and
      zidovudine, have been shown to be active in the treatment of patients with ATL. A
      small percentage of patients achieve long-lasting remissions [2,3].

PMID- 12057111
TI  - Primary central nervous system lymphomas.
AB  - Primary central nervous system lymphoma (PCNSL) is widely regarded as one of the
      primary brain tumors most amenable to treatment. Although whole brain
      radiotherapy was the cornerstone of therapy for decades, recent work clearly
      indicates that chemotherapy has become the primary focus of treatment for this
      disease. The initial treatment of PCNSL for all patients, including the elderly,
      should be chemotherapy using a high-dose methotrexate-based regimen. Although
      cranial irradiation has often been combined with methotrexate, the unacceptably
      high incidence of late neurotoxicity, particularly in older patients, has caused
      many to eliminate radiotherapy, especially in those older than age 60 years.
      Emerging data support the validity of this approach, and the development of more
      efficacious chemotherapeutic regimens has been the focus of recent research.

PMID- 12057112
TI  - Pheochromocytoma.
AB  - The only definitive therapy for patients with pheochromocytoma is surgical
      resection [1,2**]. Advances in preoperative medical management of
      hypertension/hypovolemia and improved intraoperative anesthetic care have reduced
      the operative mortality rate for pheochromocytoma to less than 5% in most series.
      In addition, accurate preoperative localization studies have eliminated the need
      for extensive exploratory laparotomy. Focused approach and laparoscopic resection
      have become the new "gold standard," with a reduced morbidity [4**]. Large or
      locally invasive pheochromocytomas may still require open resection.

PMID- 12057113
TI  - Hurthle cell carcinoma.
AB  - Patients with Hurthle cell carcinoma (HCC) of the thyroid often have aggressive
      tumors and generally have a worse prognosis than those with papillary or
      follicular thyroid carcinomas. A total thyroidectomy with ipsilateral central
      neck lymphadenectomy and a modified radical neck dissection, if central or
      lateral nodes are positive, are indicated for HCC. The completeness of this
      procedure should be assessed by radioiodine scan 3 to 4 months after surgery. Any
      thyroid remnant should be ablated with radiolabeled iodine 131 to eliminate all
      tissue at risk and to facilitate the use of serum thyroglobulin in surveillance
      for tumor recurrence. Fewer than 10% of these cancers take up radioiodine.
      Recurrent disease is treated surgically with good palliation and appreciable
      prolongation of life. Local excision and neck dissection for recurrent neck
      disease or pulmonary wedge resection for lung metastasis has been shown to be
      effective. All patients with HCC should be given thyroid hormone because most of
      these tumors have thyrotropin receptors. External beam radiation may be
      considered for patients with unresectable disease, but this is considered
      palliative.

PMID- 12057114
TI  - Gastrinoma.
AB  - Gastrinoma treatment has evolved considerably in the last 20 years. In
      particular, the advent of effective acid-reducing pharmacologic agents has
      changed the primary morbidity of this disease entity from one of acid
      hypersecretion to one of tumor growth and spread. Thus, while symptoms can be
      temporized using histamine receptor antagonists, proton pump inhibitors, or
      somatostatin analogs, cure can be effected only by surgical means. Recent
      advances in operative techniques and pre- and intra-operative imaging studies,
      including routine duodenotomy, somatostatin-receptor scintigraphy, and
      intraoperative ultrasound, have allowed for identification and subsequent
      resection of more than 95% of gastrinoma tumors. Most experts agree that all
      sporadic cases of localized gastrinoma should be excised. In addition, debulking
      of metastatic tumor may improve symptoms and survival when cure cannot be
      ascertained. There is, however, some controversy as to the surgical approach for
      gastrinoma found in the setting of multiple endocrine neoplasia, type 1. Because
      of the usual multiplicity and particular indolence of these tumors, two primary
      strategies have emerged: aggressive approaches have been advocated in an effort
      to eradicate all present and potential tumor; and less aggressive, or
      nonoperative, approaches have been suggested because it is unclear whether
      intervention offers survival or disease-free benefit in this population. We
      advocate surgical intervention for patients with gastrinoma and multiple
      endocrine neoplasia, type 1 when tumors exceed 2.5 cm in size. This tumor size
      has been associated with a higher likelihood of hepatic metastases, which
      ultimately affects survival. The role of adjuvant therapies for gastrinoma
      remains limited.

PMID- 12057115
TI  - Parathyroid carcinoma.
AB  - Although parathyroid neoplasms are common and cause primary hyperparathyroidism,
      parathyroid carcinoma is a rare entity. At times it can be difficult to diagnose.
      Patients with parathyroid carcinoma usually present with profound symptoms of
      hyperparathyroidism and highly elevated serum calcium and parathyroid hormone
      (PTH) levels. At the time of neck exploration, a large, gray-white, locally
      invasive tumor is commonly encountered. The course of patients with parathyroid
      carcinoma is variable; unfortunately, more than 50% have persistent or recurrent
      disease due to regional or distant disease. Surgical resection is the principal
      treatment for patients with parathyroid carcinoma. The optimal surgical treatment
      is en bloc tumor resection with ipsilateral thyroid lobectomy when the diagnosis
      is suspected and until it is proven otherwise. Patients who have persistent or
      recurrent parathyroid carcinoma should have localizing studies to identify loco
      regional or distant tumor sites. Reoperation in patients with localized
      parathyroid carcinoma is recommended because it relieves symptoms of
      hypercalcemia, and it normalizes serum calcium and PTH levels in most patients.
      For patients who have unresectable parathyroid carcinoma, a protocol-based
      treatment with chemotherapy and external radiotherapy should be considered.
      Additionally, second-generation bisphosphonates and the NPS R-568 calcimimetic
      agent may be useful in normalizing the serum calcium and improving symptoms of
      hypercalcemia. However, they do not treat the tumor and are rarely effective in
      the long term.

PMID- 12057116
TI  - Adrenal cortical carcinoma.
AB  - Adrenal cortical carcinoma is a rare endocrine tumor, and complete surgical
      resection is the only potentially curative treatment. Accurate preoperative
      biochemical and radiographic evaluation of the patient who presents with an
      adrenal mass optimizes patient management and facilitates a complete margin
      negative resection of the primary tumor--the most important prognostic variable
      for long-term survival. Response to mitotane or chemotherapy is modest in
      patients with advanced disease. It is hoped that an improved understanding of the
      molecular pathogenesis of this challenging tumor will lead to the development of
      novel treatment strategies.

PMID- 12057117
TI  - Primary hyperparathyroidism.
AB  - Treatment of primary hyperparathyroidism depends on a clear diagnosis based on
      biochemical confirmation. Most patients have an elevated serum total or ionized
      calcium level in association with an elevated or inappropriate serum intact
      parathyroid hormone level. The serum calcium level can be lowered by hydration
      and by a variety of pharmacologic agents. However, none of these agents is
      effective in the long-term management of primary hyperparathyroidism. The
      extraordinarily high success rate of surgery, combined with its low morbidity and
      the ever-increasing acceptance of minimally invasive techniques, makes surgical
      resection the recommended treatment for virtually all patients.

PMID- 12057118
TI  - Early stage (I, II, III) melanoma.
AB  - Metastatic melanoma beyond the regional nodes (American Joint Committee on Cancer
      stage IV) is a highly lethal disease. Few affected individuals survive beyond 5
      years despite aggressive treatment. Clearly, effective adjuvant therapies to
      prevent the development of stage IV disease in at-risk patients are worthwhile
      and acceptable to patients, even if they are associated with significant
      toxicities. Improvements in our understanding of the prognosis and staging of
      melanoma have allowed us to better categorize patients based on their risk of
      developing metastatic disease, permitting the development of logical strategies
      using adjuvant therapies with toxicity profiles that are appropriate based on the
      level of risk for recurrence. Adherence to the standards of care for the surgical
      management of melanoma patients with high-risk primary disease or regional
      disease will help optimize the benefit that can be derived from adjuvant therapy.
      Clinical trials remain critically important as we seek to improve the outcome for
      melanoma patients, but for high-risk melanoma patients outside the context of
      clinical trials, adjuvant therapy with high-dose interferon-alfa2b should be
      considered a standard treatment option.

PMID- 12057119
TI  - Metastatic melanoma.
AB  - The overall survival for patients with metastatic melanoma ranges from 4.7 to 11
      months, with a median survival of 8.5 months. Standard treatment for patients
      with metastatic melanoma has not been defined. The range of treatment options
      includes close observation, surgical resection of isolated metastases, therapy
      with dacarbazine, combination chemotherapy, and participation in clinical trials.
      Numerous chemotherapeutic agents have shown activity in the treatment of
      malignant melanoma. Dacarbazine (DTIC-Dome; Bayer Corporation, West Haven, CT)
      has a response rate of 15% to 20% and remains the reference agent for the
      treatment of metastatic disease. Additional agents with single-agent activity
      include cisplatin, (Platinol-AQ; Bristol-Myers Oncology, Princeton, NJ);
      carmustine (BiCNU; Bristol-Myers Oncology, Princeton, NJ); paclitaxel (Taxol;
      Bristol-Myers Squibb, Princeton, NJ); and docetaxel (Taxotere; Rhone-Poulenc
      Rorer Pharmaceuticals, Collegeville, PA). Temozolomide (Temodar; Schering-Plough,
      Kenilworth, NJ), which is essentially an oral form of dacarbazine but with
      greater central nervous system penetrance, is associated with a response rate of
      20%. Combination chemotherapy with or without tamoxifen has been extensively
      evaluated in patients with metastatic melanoma. Although the initial results with
      the Dartmouth regimen (dacarbazine, cisplatin, carmustine, and tamoxifen) were
      associated with overall response rates of 50% to 55% in single-institution
      studies, results from larger multicenter studies reveal responses rates ranging
      from 10% to 20%. Based on the results of several clinical trials, there is no
      evidence that the addition of tamoxifen improves the response rate. Another
      combination regimen is cisplatin, vinblastine, and dacarbazine (CVD), which is
      associated with a 20% to 25% response rate. There has been widespread interest in
      developing immunotherapies against metastatic melanoma. Interferon (IFN)-alfa and
      interleukin (IL)-2 as single agents have produced response rates in the 15% to
      20% range. Biochemotherapy, which is a combination of immunotherapy and cytotoxic
      chemotherapy, has been studied in patients with metastatic melanoma. Multiple
      phase II studies have demonstrated high response rates but unclear impact on
      overall survival. Therapy is associated with significant toxicity. Ongoing
      randomized clinical trials will clarify the role of biochemotherapy in patients
      with metastatic melanoma. Ongoing new approaches to treatment include the
      therapeutic use of vaccines alone or in combination with cytokines.

PMID- 12057120
TI  - Plasma cell leukemia.
AB  - Plasma cell leukemia (PCL) is a rare aggressive variant of multiple myeloma (MM)
      characterized by a fulminant course and poor prognosis. The median survival is
      measured in months. Therapy and prognosis partially depend on whether the disease
      presents de novo or as a secondary process involving the leukemic transformation
      of a previously diagnosed MM. Secondary PCL represents a terminal event for
      refractory/relapsed MM and is usually not responsive to any treatment modality.
      The optimal regimens for the treatment of primary PCL have not been firmly
      established. Induction with combination chemotherapy, followed by high-dose
      chemotherapy (preferably within the setting of a clinical trial), is the current
      recommended approach for eligible patients.

PMID- 12057121
TI  - Hairy cell leukemia.
AB  - The standard therapy for hairy cell leukemia (HCL) is with the nucleoside
      analogs, 2"-deoxycoformycin (dCF) or 2-chlorodeoxyadenosine (CdA), which produce
      morphologic complete remissions (CRs) in the majority of patients, although
      residual hairy cells can frequently be detected by molecular or immunologic
      techniques. Relapses continue to occur over time, but most patients respond well
      to retreatment with the same agent. The longest follow-up is for patients treated
      with dCF, where the 5- and 10-year relapse-free survival rates are 80% to 85% and
      67% to 76%, respectively. dCF is usually administered as 4 mg/m2 intravenously
      every second week until CR followed by two additional treatments for
      consolidation. CdA is administered as 0.09 mg/kg/d x 7, by continuous intravenous
      infusion, although it may be equally effective when given as daily boluses or
      subcutaneously. More recent studies have suggested that CdA, 0.15 mg/kg
      intravenously weekly x 6, produces equivalent response rates, while reducing the
      risk of febrile neutropenia (which occurs in approximately 50% of patients using
      the standard regimen). We have found this to be a very simple, safe, and
      effective regimen. Both dCF and CdA should be used with caution in the presence
      of renal or hepatic dysfunction, and both are contraindicated in the presence of
      active infection. Interferon-alfa (3 x 10(6) U subcutaneously three times per
      week for 12 months) produces inferior response rates but is less likely to cause
      febrile neutropenia. It can be considered for initial treatment for patients with
      active infection, patients at high risk of febrile neutropenia, and patients who
      cannot tolerate or are resistant to the nucleoside analogs. Splenectomy is now
      rarely performed in HCL, but it is required for splenic rupture and may be of
      value in "splenic" HCL or those with massive splenomegaly and hypersplenism. In
      preliminary studies, monoclonal antibodies directed against CD20 or CD25 also
      show activity in HCL, but their roles in this disease require further study.

PMID- 12057123
TI  - Infectious complications in chronic lymphoid malignancy.
AB  - Taking steps to minimize, prevent, and treat infection in patients with chronic
      lymphoid malignancies, especially chronic lymphocytic leukemia, has always been a
      challenge. As more patients with these diseases live longer and lead productive
      lives upon successful initial treatment, strategies for preventing infections
      have become more important. Distinguishing patients at low risk for infection
      from those at high risk is a crucial but challenging issue. Unfortunately, there
      are hardly any data on the use of prophylactic antibiotics for patients with
      chronic lymphoid malignancy (CLL). If patients cannot be enrolled in a clinical
      trial, antibiotics with co-trimoxazole should be administered when steroids are
      warranted. They should also be administered in patients who have had a documented
      infection early in the treatment course and during neutropenia. Viral infections
      remain another controversial issue in patients with CLL receiving treatment,
      especially a purine analogue. Very low CD4 counts (less than 50 cells/mL) might
      predict for reactivation for herpes zoster. Outside of depleted CD4 counts, there
      are no other means of identifying a high-risk group. Based on limited data, it
      would be reasonable to administer herpes zoster prophylaxis to patients with CD4
      counts that are severely depleted or to patients with a prior episode of zoster.
      Controversial issues still remain regarding immunoglobulin treatment,
      specifically cost, scarcity of the product, and adequate dose, which has not yet
      been established. We would consider intravenous immunoglobulin (Ig) replacement
      in patients with marked hypogammaglobulinemia (IgG less than 400 mg/dL) with more
      than two recent severe infections [1]. Lower Ig doses (240 mg/kg) have been shown
      to be equivalent to higher ones in this trial [1].

PMID- 12057122
TI  - T-small cell disorders.
AB  - A minority (less than 2%) of all lymphoproliferative disorders are derived from
      small T cells. These include T-cell prolymphocytic leukemia, T-cell granular
      lymphocytic leukemia, and mycosis fungoides/Sezary syndrome. With the possible
      exception of early-stage, skin-localized mycosis fungoides, all are considered
      incurable, although palliation can be achieved with radiation therapy,
      chemotherapy, biologic therapy, and combinations of these modalities. Of these
      disorders, mycosis fungoides is the most common; it follows an indolent, though
      gradually progressive, course that spans years. The T-cell prolymphocytic
      leukemias, in contrast, are generally refractory to treatment, with a median
      survival of typically less than 1 year. Although effective therapy remains
      elusive in most cases, the development of nucleosides as a class of
      chemotherapeutic agents and biologics, including interferon, monoclonal
      antibodies, and vitamin A derivatives, offers new hope for at least more
      effective palliation of these progressive lymphoproliferative disorders. However,
      rapid improvement in the treatment of these disorders remains hampered by the
      rarity of these individual entities. More rapid progress in treatment depends on
      national and international cooperation to accrue patients for definitive trials
      of sufficient size to evaluate new treatment options quickly.

PMID- 12057124
TI  - Chronic myelogenous leukemia in chronic phase.
AB  - Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder
      characterized by genomic instability leading to its inevitable clinical evolution
      from an easily controlled chronic phase to a terminal blastic phase. The
      molecular abnormality responsible for this disease--BCR-ABL--and the critical
      biochemical aberrations resulting from it have been studied in depth. These
      discoveries have led to the development of a molecule, STI571, that specifically
      inhibits the abnormal kinase enzymatic activity exhibited by BCR-ABL. Early
      results of clinical trials using STI571 have shown responses even in blast
      crisis. There has also been striking hematologic and cytogenetic remission rates
      in patients with advanced chronic phase disease, with very little toxicity. It is
      our opinion that this molecule will revolutionize the treatment of CML.
      Furthermore, the path leading to its discovery will become a paradigm for cancer
      therapeutics. At the time of this writing, STI571 remains investigational
      (although it is widely believed that it will be approved for clinical use in the
      United States this year ). Although suggested therapy for a disease does not
      generally incorporate medications that are still investigational, in this case,
      the impact of a still investigational agent cannot be ignored. The current data
      suggest that STI571 will be the treatment of choice for patients with advanced or
      resistant chronic phase. To date, STI571 has not been studied adequately in
      untreated CML patients. Even so, it is our feeling that, based on its compelling
      success in patients with interferon-refractory and advanced disease and on its
      benign side effect profile, it will quickly become the front-line therapy for CML
      once it becomes available. Despite the ease of administration of STI571, patients
      should continue to be encouraged to participate in clinical studies so that
      several vital issues can be resolved: 1) the percentage of untreated CML patients
      who will eventually develop molecular remissions; 2) the proportion of patients
      in whom resistance to STI571 will emerge; 3) the optimum length of treatment; and
      4) the impact on survival. Because interferon-alfa can also result in cytogenetic
      remissions, albeit in a small percent (less than 20%) of early chronic phase
      patients, it seems reasonable to suggest that patients who do not attain
      cytogenetic/molecular remissions with STI571 alone be treated with a combination
      of STI571 and interferon-alfa. Patients who are resistant to STI571 with or
      without interferon-alfa should undergo allogeneic hematopoietic cell transplant.
      Salvage therapy after transplant may include donor lymphocyte infusions,
      interferon-alfa, additional transplant, and perhaps STI571. Medications such as
      hydroxyurea appear destined to play a very limited role in CML. They may be used
      in the palliative treatment of older STI571-resistant patients or those without a
      transplant donor, although these patients may be best served by being considered
      for clinical trials of molecules, such as polyethylene glycol-interferon-alfa, on
      other novel agents.

PMID- 12057125
TI  - Autoimmunity in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is associated with the immune-mediated
      disorders autoimmune hemolytic anemia and immune thrombocytopenia. Initial
      treatment with corticosteroids is often successful in controlling these
      manifestations, but splenectomy should be considered if a rapid and complete
      response is not obtained. For those with persistent anemia or thrombocytopenia
      after splenectomy, treatment directed against the underlying CLL may be
      considered, although the use of purine analogues has also precipitated autoimmune
      hemolytic anemia. Pure red cell aplasia has been reported in CLL, and usually
      responds to immunosuppressive therapy.

PMID- 12057126
TI  - Relapsed multiple myeloma.
AB  - The treatment of relapsed multiple myeloma remains a challenge for clinicians.
      Most salvage therapies result in transient responses, with median survival from
      relapse ranging from 6 to 18 months. No randomized trials comparing salvage
      therapies have been performed. In the absence of a "gold standard" salvage
      therapy, relapsed patients should be considered for clinical trials. In light of
      the recent observation that thalidomide alone brings about a 30% to 35% response
      rate with manageable toxicities, this is the most promising single agent
      available to treat relapsed disease. The maximum effective dose appears to be 400
      mg/d; virtually all responses are evident within 2 months of starting therapy.
      Combination therapy of thalidomide with pulse dexamethasone or other
      chemotherapeutic agents has shown promise in pilot trials. Even with thalidomide
      responsive disease, the response duration is brief, ranging from 3 to 6 months.
      Therefore, the authors recommend that patients under the age of 78 years who have
      acceptable physiologic organ function, chemotherapy-sensitive disease, third
      party financial coverage, and adequate hematopoietic stem cells be considered for
      high-dose therapy with autologous hematopoietic stem cell transplant. High-dose
      therapy with hematopoietic stem cell transplant provides the highest response
      rate, response duration, and survival compared with historical controls treated
      with conventional therapy. Patients under the age of 70 years who have human
      leukocyte antigen-compatible donors should be considered for immune-based therapy
      using nonmyeloablative preparative regimens with allogeneic hematopoietic stem
      cell transplant.

PMID- 12057127
TI  - Bone disease in myeloma.
AB  - The major clinical manifestation of multiple myeloma results from osteolytic bone
      destruction. The only currently Food and Drug Administration-approved drug for
      the treatment of the bony complications of multiple myeloma is monthly
      intravenous pamidronate at a dose of 90 mg infused over 4 hours. Recent studies
      have shown the safety of 2-hour infusions. A randomized trial comparing
      pamidronate to placebo continued to show benefits throughout the 21-month trial.
      Although the duration of therapy has not been firmly determined, it is likely
      that discontinuation of this drug will be met by enhanced bone loss and an
      increased risk of bony complications for these patients. Thus, it is recommended
      that the drug be continued indefinitely. Support for this recommendation also
      comes from the reduced bone density observed in women with postmenopausal
      osteoporosis following the withdrawal of bisphosphonate treatment. Recent
      attempts to give higher doses, more frequent infusions (every 2 weeks or less),
      or more rapid infusions (1 hour or less) of pamidronate have occasionally been
      associated with albuminuria and azotemia. These modifications should therefore be
      avoided. Importantly, the drug can be safely administered at 90 mg monthly to
      patients with poor renal function. The use of pamidronate for myeloma patients
      without lytic bone involvement or with Durie-Salmon stages I or II disease has
      not been evaluated. However, it is recognized that most patients with earlier
      stages of disease or without lytic bone involvement also develop bony
      complications. There is no reason to believe that these patients would not
      benefit from monthly intravenous infusions of pamidronate. The potential
      antimyeloma effect of this agent is another reason to administer this drug in
      these types of patients. Thus, it is our practice to administer monthly
      pamidronate to myeloma patients regardless of stage or bone involvement. However,
      trials evaluating oral bisphosphonates have produced inconsistent clinical
      results, probably as a result of the erratic and scanty poor absorption as well
      as poor oral tolerability of these drugs. Although these oral agents may be
      useful in some patients, it is impossible to identify which myeloma patients will
      benefit from orally administered bisphosphonates. The more potent nitrogen
      containing bisphosphonate zoledronic acid more effectively reverses hypercalcemia
      of malignancy than pamidronate, and it appears promising in reducing bone loss in
      cancer patients. However, its efficacy in preventing skeletal complications is
      still being evaluated. Many other types of new agents are in early clinical
      trials, but their efficacy remains unproven at the present time.

PMID- 12057128
TI  - Ovarian tumors of low malignant potential.
AB  - Ovarian tumors of low malignant potential (LMP) differ from epithelial ovarian
      carcinoma in etiology, molecular biology, and prognosis. LMP tumors are not
      precursor lesions to ovarian carcinoma. Treatment is primarily surgical. Women
      found to have an ovarian tumor of LMP should undergo removal of the involved
      adnexa; surgical staging; and cytoreductive surgery. Women in the reproductive
      years should be given the option of conservative surgery, preserving the
      contralateral adnexa and uterus. There is no proven benefit to adjuvant
      chemotherapy or radiotherapy after primary surgery. In most cases, the diagnosis
      of an ovarian tumor of LMP conveys good prognosis, with excellent long-term
      survival.

PMID- 12057129
TI  - Advanced ovarian cancer.
AB  - Ovarian cancer spreads early in the disease into the abdomen. An en bloc
      resection of the tumor, according to surgical principle, is not possible in
      patients with high-stage ovarian cancer. At surgery, large pelvic tumor lesions
      are found together with multiple tumor lesions involving the omentum, bowel, and
      mesentery together with a diffuse peritoneal carcinomatosis and diaphragmatic
      involvement. A multimodality approach with cytoreductive surgery and taxol
      platinum-based chemotherapy is therefore the mainstay of treatment of advanced
      ovarian cancer. The size of residual disease after surgery is one of the most
      important prognostic factors for survival. Patients with an optimal tumor
      cytoreduction (residual lesions smaller than 1 cm) have a significant longer
      survival (almost two times the median survival) than patients with larger
      residual lesions. This holds true even for patients with International Federation
      of Gynecology and Obstetrics (FIGO) stage IV disease. Patients in whom all
      macroscopic tumor is resected do have the longest survival. The 2-year survival
      of patients with a radical resection of all macroscopic tumors is 80%, in
      contrast to less than 22% for the patients with lesions larger than 2 cm. An
      optimal primary cytoreductive surgery can generally be performed in 30% to 50% of
      patients. Only in more experienced gynecologic oncology centers is the percentage
      as high as 85%, but sometimes at the cost of an increased morbidity and even
      mortality. The worse prognosis of the patients with a suboptimal primary
      cytoreductive surgery can be improved by an interval cytoreductive surgery after
      platinum-containing induction chemotherapy. The median survival and progression
      free survivals are significantly lengthened by cytoreductive surgery. After more
      than 5-years follow-up there is still a significant survival benefit: the 5-year
      survival of the surgery patients was 24% versus 13% for the no-surgery patients
      (P = 0.0032). All patients, including those with unfavorable prognostic factors
      (stage IV disease, peritonitis carcinomatosis, or ascites at primary surgery),
      and even patients with stable disease after induction chemotherapy, seem to
      benefit from interval cytoreductive surgery. The increase in progression-free
      survival and overall survival does outweigh the morbidity associated with
      interval debulking surgery, which is not different from those associated with
      primary surgery.

PMID- 12057130
TI  - New drugs in gynecologic cancer.
AB  - The implementation of new drug treatments has improved the prognosis for advanced
      cancers of the cervix, uterus, and ovary. Platinum analogs are the most effective
      drugs in the treatment of ovarian cancer. Other drugs, such as oxaliplatin, have
      been proposed as a rational treatment of platinum refractory ovarian cancer.
      Epothilones are also being studied in clinical trials, as are histone deacetylase
      inhibitors. Several promising agents may soon receive Food and Drug
      Administration approval.

PMID- 12057131
TI  - Endometrial carcinoma.
AB  - Endometrial cancer is a common tumor of the female genital tract. The majority of
      women diagnosed with endometrial cancer present with early-stage disease.
      Although the optimal treatment for these patients requires hysterectomy, the use
      of lymphadenectomy is controversial. Growing scientific data support the use of
      lymphadenectomy in all patients diagnosed with endometrial cancer. When performed
      by an experienced surgeon, pelvic and para-aortic lymphadenectomy is a safe and
      potentially therapeutic procedure that provides prognostic information to the
      patient and physician. This information allows appropriate, cost-effective
      treatment strategies to be created for all women with endometrial cancer.

PMID- 12057132
TI  - Phyllodes tumors of the breast.
AB  - Phyllodes tumor is a rare fibroepithelial neoplasm of the breast with a very
      variable, but usually benign, course. Formerly known as cystosarcoma phyllodes,
      the designation "phyllodes tumor" with appropriate qualification regarding
      malignant potential based on pathologic features is now the agreed-upon term. The
      most important diagnostic distinction is from fibroadenoma--phyllodes tumors
      require complete excision with free margins even when pathologic features suggest
      benignity because of a proclivity to local recurrence. The most important
      component of therapy is wide surgical excision, and mastectomy is necessary only
      when free margins cannot be achieved without it. Involvement of axillary nodes is
      rare, and axillary dissection is not indicated. The role of radiation therapy and
      chemotherapy is not established and has not been studied in randomized trials due
      to the rarity of the tumor. At present, there is no consensus that patients with
      high-grade phyllodes tumors of the breast will benefit from either of these
      modalities.

PMID- 12057133
TI  - Occult breast cancer and axillary mass.
AB  - Occult breast cancer presenting with axillary metastases is an unusual
      presentation and can be a diagnostic and therapeutic challenge. A comprehensive
      work-up, including mammogram, sonogram, magnetic resonance imaging, and even
      pathologic examination of the mastectomy specimen may not disclose the primary
      tumor in up to one third of patients. Traditionally, occult breast cancer is
      treated with total mastectomy and axillary dissection, but accumulating data
      suggest that primary breast irradiation following axillary dissection may provide
      an equivalent survival with the advantage of breast conservation. Occult breast
      cancer patients are eligible for adjuvant chemotherapy and radiation as stage II/
      III node-positive patients would be treated. Overall, the prognosis for occult
      breast cancer is equivalent to or slightly better than staged counterparts with
      detectable primary breast tumors.

PMID- 12057134
TI  - Operable breast cancer.
AB  - Breast cancer is the most common malignancy among American women. As a result of
      widespread screening, most patients present with operable breast cancer that is
      treated with curative intent. It is well established that the appropriate use of
      adjuvant therapy improves the disease-free and overall survival of patients with
      breast cancer. Adjuvant systemic therapy options include tamoxifen for hormone
      receptor-positive patients, and systemic polychemotherapy. It is standard
      clinical practice to administer adjuvant systemic therapy to patients with node
      positive and high-risk, node-negative breast cancer.

PMID- 12057135
TI  - Primary soft tissue sarcoma of the breast.
AB  - Primary soft tissue sarcoma (STS) of the breast is a rare and heterogeneous
      disease. The rarity of this tumor limits most studies to small retrospective case
      reviews and case reports. The optimal treatment of primary STS of the breast can
      best be determined through multidisciplinary discussions prior to the initiation
      of therapy. Whether chemotherapy is indicated is primarily determined by tumor
      size. There is evidence that tumors larger than 5 cm are associated with an
      elevated risk of systemic failure and a poor prognosis. Negative surgical margins
      are more important for local recurrence and overall survival than is the extent
      of surgical resection. Thus, neoadjuvant chemotherapy should be considered in
      order to shrink the tumor and help obtain negative surgical margins. After
      surgical resection, patients with chemosensitive tumors should undergo additional
      adjuvant chemotherapy to treat micrometastatic disease. Patients with tumors less
      than 5 cm that are easily resectable should undergo complete resection to the
      extent required to provide negative surgical margins. Radiation therapy should be
      used to improve local control in cases in which the tumor is larger than 5 cm and
      in cases with positive surgical margins. The appropriate treatment of primary STS
      of the breast requires a multidisciplinary approach necessitating experienced
      surgeons, pathologists, radiotherapists, and medical oncologists.

PMID- 12057136
TI  - Locally advanced head and neck cancer.
AB  - The simultaneous administration of chemotherapy and radiation has produced a
      significant impact on the treatment of advanced squamous cell carcinomas of the
      head and neck. Although no single regimen has emerged as the "standard" approach,
      recent trials have consistently demonstrated the superiority of combined
      treatment programs over radiotherapy alone for local tumor control and overall
      survival. Moreover, multimodal treatment has emerged with important ancillary
      goals of organ preservation, improved cosmesis, and enhancement of quality of
      life. With improving survival in all stages of disease, much attention can be
      given to identifying effective measures to reduce the risk of metachronous
      primary cancers in this high-risk group.

PMID- 12057137
TI  - Locally advanced nasopharyngeal cancer.
AB  - The Head and Neck Cancer Intergroup phase III clinical trial (Int 0099) for
      patients with locally advanced, squamous cell carcinomas (SCC) of the nasopharynx
      (or NPC) has been recently completed in the United States. The results of this
      study have defined the new standard of treatment for the group of patients
      studied. Patients with untreated, locally advanced stages III and IV NPC were
      randomized to a conventional course of radiation, or to radiation given
      concurrently with chemotherapy followed by three courses of combination
      chemotherapy. The 3-year progression-free survival (PFS) and overall survival
      (OS) were 24% versus 69% (P < 0.001) and 46% versus 76% (P < 0.001) for the
      control and experimental groups, respectively. Recent updates of these survival
      figures show that they have not changed appreciably. The considerable improvement
      in OS versus PFS for the patient group receiving radiation alone is accounted for
      primarily by re-treatment with concurrent radiation-chemotherapy, combination
      chemotherapy, and isolated salvage neck dissections. Highly significant
      differences in local control (41% vs 14%) and distant metastases (35% vs 13%)
      were demonstrated in favor of the chemoradiation treatment arm. The median age
      for these patients was 51 years, with a 2:1 male to female ratio. Although many
      patients had a significant history of tobacco exposure with or without alcohol
      use or abuse, only 24% had keratinizing or well-differentiated squamous (World
      Health Organization I) type tumors. Whether these results can be extrapolated to
      the more common Asian variety (WHO II and III) of advanced NPC must be addressed
      in future clinical trials.

PMID- 12057139
TI  - Superior sulcus tumors.
AB  - Superior sulcus tumors (also known as Pancoast's tumors) are an unusual
      presentation of non-small cell lung cancer (NSCLC) that are often initially
      misdiagnosed. Accurate and thorough staging is necessary prior to treatment and
      typically includes magnetic resonance imaging if a surgical approach is being
      considered. Standard therapy has been induction radiation therapy followed by
      resection, which results in a 5-year survival of about 30%. Complete resection
      remains the key to long-term survival in localized NSCLC but is difficult to
      achieve with superior sulcus tumors due to early invasion of bone and to vascular
      and nervous structures at the apex of the chest. Complete resection has been
      enhanced by using an anterior trans-cervicomediastinal approach that facilitates
      resection of anterior-based tumors that invade the subclavian vessels. Recently,
      induction chemoradiotherapy has been reported to enhance complete resection rates
      and improve survival compared with historical controls and is likely to become
      the new standard treatment for localized superior sulcus tumors.

PMID- 12057138
TI  - Locally advanced non-small cell lung cancer.
AB  - Locally advanced non-small cell lung cancer remains a paradoxical entity to
      manage. Although this type of cancer is confined to the thorax and is ostensibly
      curable, most patients presenting at this stage of disease eventually succumb to
      it. The accepted therapy presently includes chemotherapy and radiation. The exact
      agents, schedules, and combinations need to be defined further, although
      cisplatin has become the widely viewed standard cytotoxic drug in this setting.
      Notwithstanding, newer chemotherapeutic and biologic agents are being extensively
      tested to find less toxic options with greater efficacy. Drugs that are gaining
      widespread approval include carboplatin, paclitaxel, gemcitabine, and
      vinorelbine. At the same time, advances in radiation therapy are triggering a
      revolution in dose intensity and scheduling that will one day offer superlative
      local control.

PMID- 12057140
TI  - Advanced non-small cell lung cancer.
AB  - The treatment of advanced non-small cell lung cancer requires histologic proof of
      diagnosis, careful staging, and assessment of each patient's performance status
      and comorbidities. For patients with stage IIIB (pleural effusion) and stage IV
      disease who have a Cancer and Leukemia Group B performance status (PS) of 0 to 1,
      appropriate management consists of combination chemotherapy with a platinum
      (either cisplatin or carboplatin) combined with paclitaxel, gemcitabine,
      vinorelbine, docetaxel, or CPT-11. Dosages and schedules previously established
      by large phase II or phase III studies should be followed. Variations in the
      toxicity patterns, schedules of administration, and economic considerations
      should guide the selection of the specific regimen. For patients who maintain a
      good performance status after first-line chemotherapy, second-line treatment may
      be considered. Current evidence supports the use of docetaxel as second-line
      treatment if the patient has not previously received this drug. Gemcitabine and
      paclitaxel may also have activity in this setting. Vinorelbine, ifosfamide, and
      CPT-11 appear to be inactive as second-line therapy for patients who have
      previously received platinum-based chemotherapy. For patients with a PS of 2,
      single-agent chemotherapy with vinorelbine, gemcitabine, or a combination of the
      two should be considered. Patients with poor performance status should be treated
      with supportive measures designed to relieve pain and acute complications because
      any tumor-directed therapy has limited benefit. Special situations exist in which
      curative therapy for metastatic disease is a possibility. Patients who present
      with solitary sites of metastatic disease, particularly after a long disease-free
      interval and in the CNS may undergo definitive surgery or radiotherapy with
      curative intent. Some have also reported favorable outcomes for patients with
      solitary adrenal or bone metastases as well. Surgical treatment or definitive
      radiotherapy should not be employed unless a thorough restaging evaluation is
      performed that includes computed tomography scan of the chest and abdomen through
      adrenals, brain magnetic resonance imaging, and positron emission tomography
      scan. A plethora of new agents targeting angiogenesis, tumor invasiveness, the
      hypoxic environment of tumors, and the cell cycle are currently in development.

PMID- 12057141
TI  - Limited stage small cell lung cancer.
AB  - The management of limited stage small cell lung cancer begins with a firm
      pathologic diagnosis and careful staging. Patients with adequate pulmonary
      function, ambulatory performance status, and no evidence of metastatic disease
      outside a "tolerable" local radiotherapy volume should have consultation from
      both medical and radiation oncology disciplines for planning of integrated
      therapy. The chemotherapy prescription recommended is cisplatin plus etoposide at
      standard doses for four chemotherapy cycles. Thoracic irradiation should be
      administered concurrently with the first or second cycle of cisplatin and
      etoposide. Patients with complete response and excellent partial response should
      receive prophylactic cranial irradiation after completion of all chemotherapy.

PMID- 12057142
TI  - Extensive stage small cell lung cancer.
AB  - Small cell lung cancer is a rapidly proliferating, biologically aggressive form
      of lung cancer that has a short survival without treatment. Chemotherapy is the
      foundation of the therapeutic approach to patients with small cell lung cancer.
      Most patients present with extensive disease, and, although few patients are
      cured, significant improvement in survival is possible with modern chemotherapy.
      The role of radiation therapy in extensive disease is palliative, and surgery has
      little role in patient management. The standard chemotherapy regimen for patients
      with small cell lung cancer has become either cisplatin or carboplatin with
      etoposide. Second-line chemotherapy regimens are moderately effective in patients
      previously responding to initial chemotherapy. Newer chemotherapy agents show
      promise, but few randomized trials have been completed in extensive disease.
      Physicians should be encouraged to include their patients with extensive small
      cell lung cancer in the evolving clinical trials.

PMID- 12057143
TI  - Superior vena cava syndrome.
AB  - Lung cancer is the most common cause of superior vena cava syndrome (SVCS) and
      requires timely recognition and management. The syndrome is rarely an oncologic
      emergency in the absence of tracheal compression and airway compromise. Treatment
      depends on the etiology of the obstructive process. Treatment should also be
      individualized and should not be undertaken until a diagnosis is obtained. Most
      patients with SVCS secondary to lung cancer can be treated with appropriately
      directed chemotherapy or radiotherapy. With the refinement of endovascular
      stents, percutaneous stenting of the SVC is being increasingly used as primary
      treatment modality. Thrombotic occlusion can be treated with appropriate lytic
      agents. In rare circumstances, surgical decompression can be performed; bypass or
      replacement of the SVC results in immediate improvement in the majority of cases
      and can be accomplished with low morbidity.

PMID- 12057144
TI  - Malignant pleural effusions.
AB  - Malignant pleural effusions contribute to considerable morbidity in cancer
      patients and generally portend an overall poor prognosis. Treatment of malignant
      pleural effusions is palliative; therefore, quality of life issues, as well as
      the risks and benefits of the therapeutic options, become more critical. In my
      opinion, factors such as in patient versus outpatient management and associated
      procedural discomfort are important in the decision-making process, and the
      patient should participate in these subjective considerations. It is difficult to
      compare results and determine the true efficacy of different techniques and
      agents because endpoints and response criteria as well as the extent and method
      of follow-up vary. In addition, the etiology of the primary complaint, dyspnea,
      is frequently multifactorial. However, malignant effusions recur, and therefore
      repeated thoracentesis, especially if the fluid rapidly reaccumulates, is usually
      not a good long-term solution unless the patient's overall prognosis and current
      condition prohibits a more invasive option. The standard option for recurrent
      effusions is insertion of a chest tube. If the lung re-expands, chemical
      pleurodesis is attempted to achieve adherence of the visceral to the parietal
      pleura. Sterilized talc is the best sclerosant; it has good efficacy and cost
      effectiveness and can be administered easily as a slurry at the bedside via a
      chest tube with minimal patient discomfort and without more aggressive and
      invasive procedures.

PMID- 12057145
TI  - Pancreatic cancer.
AB  - Optimal therapy for pancreatic adenocarcinoma requires surgical removal with
      tumor-free margins. Superior outcomes have been reported for high-volume centers
      incorporating a multidisciplinary approach. Postoperative ("adjuvant")
      chemotherapy and radiation should be considered in patients with successfully
      resected primary tumors. Combined modality treatment with chemotherapy and
      radiation should be considered for locally advanced, unresectable tumors.
      Gemcitabine can provide symptom relief and a modest improvement in survival for
      patients with metastatic disease. Strict attention to relief of symptoms such as
      pain, depression, anorexia/cachexia, and jaundice is essential in all patients
      with pancreatic cancer. All patients with pancreatic cancer should be encouraged
      to enter clinical trials of new therapies, given that long-term survival for all
      stages remains poor.

PMID- 12057147
TI  - Sphincter preservation in rectal cancer.
AB  - Distal rectal cancer poses two challenges to the oncologist: local tumor control
      and sphincter preservation. The abdominoperineal resection (APR), long considered
      the standard treatment of tumors with a distal edge located up to 6 cm from the
      anal verge, provides local control in many patients but results in sphincter loss
      with a permanent colostomy. This is a critical limitation. Consequently, there
      has been significant interest in sphincter-conserving approaches, frequently
      combining chemoradiation with surgery. These approaches have evolved along two
      fronts. For patients with small rectal cancers confined to the rectal wall, local
      excision techniques with and without chemoradiation may offer comparable local
      control and survival rates as an APR and preserve sphincter function. For
      patients with larger and more invasive tumors of the distal rectum where local
      excision is inappropriate, preoperative chemoradiation promotes tumor regression
      and may facilitate a resection sparing the sphincter with a coloanal anastomosis.
      Preliminary results from single institution studies appear promising. In both
      these settings (favorable and more invasive rectal cancer), chemoradiation is
      employed to compensate for the limitations of the sphincter-preserving surgical
      technique. In local excision procedures, the excision margins are invariably
      small, and the mesorectum (lymphatics, soft tissue) surrounding the tumor is not
      excised. For patients undergoing resection with coloanal anastomosis, there are
      narrow radial and distal surgical margins. With these approaches of
      chemoradiation and sphincter-sparing surgery, satisfactory local control and
      survival with avoidance of colostomy are possible for many patients with distal
      rectal cancer.

PMID- 12057146
TI  - Gastroesophageal junction adenocarcinoma.
AB  - The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is
      increasing in association with the epidemiologic rise in distal esophageal
      adenocarcinoma and gastric cardial (AEG type III) tumors. The overall survival
      rate is poor in most patients with AEG because lymph node or visceral metastases
      are frequently present at the time patients become symptomatic. A few patients
      are identified early in the disease because of screening for gastroesophageal
      reflux and Barrett's esophagus. Early stage AEG (T1N0 or T2NO, carcinoma in situ,
      or severe dysplasia ) can in many instances be cured with surgery alone. Ablative
      treatments for early stage AEG, including endoscopic fulguration by cautery and
      laser or photodynamic therapy, are investigational at this time. Locoregionally
      advanced AEG (T3, T4, N1, or M1a ) without distant systemic metastases (M1b) has
      a poor overall survival rate with surgery alone or definitive chemotherapy and
      radiation therapy without surgery. Analysis of the use of multimodality treatment
      strategies for locoregionally advanced AEG types I and II have demonstrated
      improved survival rates in two small phase III trials with preoperative
      concurrent chemoradiotherapy followed by surgical resection. In contrast, three
      small phase III trials with preoperative concurrent or sequential
      chemoradiotherapy in patients with predominantly squamous cell carcinoma did not
      demonstrate any clear survival advantage. Additionally, a randomized phase III
      study evaluating preoperative chemotherapy without radiation therapy in
      esophageal cancer (predominantly adenocarcinoma) has demonstrated no survival
      benefit. In light of these results, additional large randomized phase III studies
      are needed to confirm the potential benefit of preoperative concurrent
      chemoradiotherapy. At the present time, preoperative chemoradiotherapy remains
      investigational. For locoregionally advanced gastric adenocarcinoma, including
      AEG type III, postoperative concurrent 5-fluorouracil (5-FU)-based
      chemoradiotherapy is associated with improved survival as demonstrated in a
      recently completed random assignment trial (INT 0116). As a result, surgery with
      postoperative chemoradiotherapy has recently become the standard of care for
      patients with AJCC stage II and III gastric adenocarcinoma (including patients
      with AEG type III). Metastatic AEG (M1b) should be treated with palliative
      chemotherapy (in good performance patients) or supportive care (poor performance)
      in asymptomatic patients. Radiation therapy and endoscopic stent placement
      (expandable wire mesh) can be used to palliate dysphagia in patients with M1b
      disease. The development of expandable stents and improved radiotherapy has
      obviated surgical bypass to palliate patients with symptomatic, metastatic AEG.

PMID- 12057148
TI  - Hepatocellular carcinoma.
AB  - Early detection of hepatocellular carcinoma (HCC) is feasible, particularly in
      patients known to be at risk from chronic hepatitis and chronic liver disease.
      The optimal surveillance strategy is unknown. HCC usually presents as an
      incurable disease even when detected on surveillance. Surgical resection is the
      treatment of choice, but the coexistence of chronic liver disease and the
      insidious nature of HCC make it unresectable in most patients. Orthotopic liver
      transplantation for selected patients or ablative techniques may offer an
      opportunity to render patients disease-free even if the tumor is unresectable.
      There are numerous therapies offered to patients with unresectable HCC, including
      chemotherapy, hormonal therapy, and regional intra-arterial treatments. While
      potentially palliative, none of these approaches has been demonstrated to prolong
      survival in these patients. If possible, the treatment of patients with HCC
      should be done on clinical trials.

PMID- 12057149
TI  - Advanced renal cell carcinoma.
AB  - For most patients with advanced renal cell carcinoma, treatment remains
      palliative. Standard chemotherapy used in the treatment of other types of cancers
      has proven ineffective in the treatment of this disease. High-dose interleukin-2
      (IL-2) is the only regimen that has consistently shown benefit in advanced renal
      cell carcinoma. However, only a minority of patients is eligible for this
      treatment due to its toxicity, and only 15% to 20% of eligible patients respond
      with 7% long-term complete responses. Most investigational strategies in the
      treatment of advanced renal cell carcinoma are evaluating immunotherapeutic
      approaches, but participation of patients in clinical trials evaluating new novel
      cytotoxic agents or antiangiogenic agents remains an important option.

PMID- 12057150
TI  - Localized bladder cancer.
AB  - Transitional cell carcinoma (TCC) of the bladder makes up 90% of bladder cancers.
      The approach to the management of localized TCC includes accurate clinical and
      histologic diagnosis and staging with pathologic material obtained through
      endoscopy. Once the diagnosis of superficial TCC has been established,
      histologically based prognostic factors guide which therapy or combination of
      therapies is indicated in the management of individual patients. Surgery alone
      (transurethral resection) is appropriate initial therapy for noninvasive
      papillary TCC. For lamina propria invasive tumors and carcinoma in situ,
      intravesical immunotherapy with bacille Calmette-Guerin (BCG) is often the first
      line of treatment to decrease tumor recurrence and to possibly decrease
      progression and improve survival. Intravesical chemotherapy and interferon are
      alternative therapies that can also decrease recurrence rates. For BCG-refractory
      TCC, durable response rates with alternative intravesical therapies are low. For
      superficial TCC that is refractory to endoscopic procedures and intravesical
      agents or for disease progression, radical cystectomy with neobladder formation
      or other forms of urinary diversion is the treatment of choice.

PMID- 12057151
TI  - Localized prostate cancer.
AB  - Much controversy still surrounds the diagnosis and treatment of localized
      prostate cancer. Urologists generally believe that early detection and aggressive
      surgical therapy saves lives despite the absence of confirmatory randomized
      trials. Furthermore, a recent survey of radiation oncologists and urologists
      revealed marked polarization toward their own specialties when asked how they
      would counsel patients on therapy for newly diagnosed localized disease. Some
      issues are not controversial, however. There is general agreement that
      pretreatment tumor characteristics, including serum prostate-specific antigen
      level at diagnosis, tumor grade, and clinical stage as judged by digital rectal
      examination, are important prognosticators for treatment outcomes independent of
      the type of treatment. Also, there is sufficient experience with standard
      therapies (radical prostatectomy and external beam radiotherapy) to counsel
      patients on the chance for cure and the expected incidence of acute and chronic
      toxicities. A comparative evaluation of various therapies for prostate cancer
      should include consideration of cancer control, acute toxicity, treatment-related
      quality of life issues, salvage of treatment failures, and cost. Within this
      context, we believe that newly diagnosed patients should be counseled on all
      available treatment options before embarking on a course of therapy.

PMID- 12057153
TI  - Malignant gliomas.
AB  - Gliomas are a heterogeneous group of neoplasms that comprise the majority of
      tumors originating in the central nervous system (CNS). In adults, the most
      frequently encountered of these are high-grade or malignant neoplasms of
      astrocytic and oligodendrocytic lineage, ie, anaplastic astrocytoma (AA),
      glioblastoma multiforme (GBM), and anaplastic oligodendroglioma (AO),
      respectively. Tumors of mixed lineage are also seen, the most common of which is
      designated anaplastic oligoastrocytoma (AOA). Standard treatment for these tumors
      is typically surgery, followed by radiation then chemotherapy. Surgery is
      required for a definitive histopathologic diagnosis, which in turn will dictate
      subsequent therapy options. Moreover, aggressive tumor resection improves
      survival outcomes, and in many cases, the patient's neurologic function. We
      generally advocate the safest, maximal resection attainable for patients with
      these tumors as a way to improve prognosis. In almost all cases, surgery is
      followed by radiation therapy. Postsurgical irradiation is the most effective
      treatment currently available for improving survival. There is also mounting
      evidence to suggest that additional radiation, given in the form of brachytherapy
      or radiosurgery, at initial diagnosis as a "boost" to standard radiation or at
      tumor recurrence, may provide added improvement in survival outcome. Radiosurgery
      and brachytherapy are therapies often used to treat eligible patients at this
      institution. Adjuvant chemotherapy, conventionally given after radiation, may
      offer a modest survival benefit in some patients with GBM.
      Bischloroethylnitrosourea (BCNU) is the typical first-line agent used, but
      chemotherapy seems to be most beneficial in young patients, with little if any
      impact on survival for patients over 60 years old. At this institution, we often
      defer treatment with adjuvant chemotherapy for elderly patients with GBM due to
      lack of efficacy and the attendant risk with chemotherapy. For anaplastic
      astrocytomas, oligodendrogliomas, and oligoastrocytomas, a commonly accepted
      standard is adjuvant chemotherapy following irradiation with the three-drug
      regimen--procarbazine, CCNU, and vincristine (PCV). This is due to an earlier
      clinical trial that showed a survival advantage in patients treated with adjuvant
      PCV compared with patients that received BCNU. However, recent data suggest that
      treatment with either PCV or BCNU may be appropriate. Both regimens now appear to
      have equal efficacy for anaplastic gliomas in light of a more recent analysis
      done with larger numbers of patients. AOs are a unique case with respect to tumor
      chemosensitivity and patient survival. Molecular studies have identified a
      subpopulation of patients with AO whose tumors have lost chromosomes 1p and 19q.
      Patients with this molecular pattern have an exceptional responsiveness to PCV
      chemotherapy and have prolonged survival. Currently, trials are being conducted
      to confirm this finding and to determine the best treatment regimen for these
      patients, with particular regard to the timing of radiation and chemotherapy.

PMID- 12057152
TI  - Brain metastases.
AB  - Brain metastases are an increasingly common complication in patients with
      systemic cancer. The optimal treatment for each patient depends on careful
      evaluation of several factors: the location, size, and number of brain
      metastases; the patient's age, general condition, and neurologic status; and the
      extent of systemic cancer to name a few. For patients with a single brain
      metastasis and limited systemic disease, the standard treatment is surgical
      resection followed by whole brain radiation therapy. In patients with a small,
      single metastasis, stereotactic radiosurgery is probably comparable to surgery.
      Patients with several metastases (up to three) and controlled systemic disease
      can be treated with whole-brain radiation and stereotactic radiosurgery. Patients
      with multiple metastases (more than three) are generally treated with whole-brain
      radiation alone. Radiosurgery is effective in treating patients with a limited
      number of recurrent brain metastases and stable systemic diseases. Surgery may
      have a role in patients with a large symptomatic recurrent lesion producing mass
      effect. Reirradiation and chemotherapy may have a limited role in patients with
      multiple recurrent metastases.

PMID- 12057155
TI  - Pericardial mesothelioma.
AB  - Primary pericardial mesothelioma is a rare but lethal disease. Altogether there
      are about 150 cases reported in the literature. In most cases the diagnosis is
      made at autopsy or postoperatively. Clinical signs and symptoms are typically
      nonspecific and are similar to compromised cardiac function. Surgical resection
      remains the main treatment modality. When the disease is localized and completely
      resected, long-term survival can result. Most often the tumor invades the
      myocardium or the great vessels and therefore is at best palliative in relieving
      pericardial tamponade or constriction. Addition of chemotherapy or radiation has
      been disappointing. Newer therapeutic approaches for malignant pleural
      mesothelioma are likely to influence the treatment of pericardial mesothelioma in
      the future.

PMID- 12057154
TI  - Fibrous tumors of the pleura.
AB  - Fibrous tumor of the pleura is a rare tumor arising from mesenchymal cells
      underlying the visceral or parietal pleura. The tumor may have benign or
      malignant histological features, but these do not always predict the clinical
      behavior of the tumor. In most cases, the tumor appears pedunculated, and simple
      resection of the tumor is curative even if significant cellular atypia is
      present. In contrast, some tumors with a broad base of attachment may recur and
      occasionally become malignant. Complete surgical resection is the mainstay of
      therapy for both benign and malignant fibrous tumors of the pleura. When
      resection is incomplete or impossible, external radiation therapy with or without
      chemotherapy is recommended.

PMID- 12057156
TI  - Peritoneal mesothelioma.
AB  - Malignant peritoneal mesothelioma is an aggressive neoplasm that rapidly spreads
      within the confines of the abdominal cavity to involve most accessible peritoneal
      and omental surfaces. Current treatments are unsatisfactory, and new approaches
      are needed. We have noted prolonged survival in selected patients after intensive
      multimodality treatment. Our current experimental regimen includes initial
      laparotomy with omentectomy, resection of peritoneal implants, and placement of
      bilateral peritoneal Port-a-Caths (Sims Deltec, Inc., St. Paul, MN); repeated
      courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and
      interferon gamma; second-look laparotomy and intraoperative hyperthermic
      perfusion with mitomycin and cisplatin; and whole abdominal radiation. Patients
      with peritoneal mesothelioma who are not candidates for this approach can
      sometimes be palliated with systemic (intravenous) chemotherapy using doxorubicin
      or mitomycin, alone or in combination with cisplatin or carboplatin. Newer agents
      such as gemcitabine and multitargeted antifolate (pemetrexed disodium, LY231514)
      show promise of greater effectiveness.

PMID- 12057157
TI  - Malignant pleural mesothelioma.
AB  - Despite innumerable trials of surgery, radiotherapy, and countless
      chemotherapeutic drugs, it is unclear whether any intervention has had a
      significant impact on more than a few highly selected patients with malignant
      pleural mesothelioma. Because most patients die of respiratory failure from
      extensive disease progression in the thorax, treatment usually includes attempts
      at local control. Unfortunately, radiotherapy is associated with significant
      complications in pleural mesothelioma, and surgery is feasible in only a small
      percentage of patients. Although there have been several single-institution
      reports of combined-modality therapy with extrapleural pneumonectomy,
      postoperative radiation, and chemotherapy in which prolonged survival has been
      observed, most patients with malignant pleural mesothelioma have locally advanced
      disease, advanced age, or comorbid medical illnesses that preclude aggressive
      surgery. Therefore, the use of a systemic anticancer agent is the only treatment
      option for most patients with malignant pleural mesothelioma. Evaluation of
      effective chemotherapy regimens for this disease has been hampered by many
      factors. Because mesothelioma is an uncommon malignancy, most studies have
      enrolled small numbers of patients, and few trials have been randomized. The
      disease is heterogeneous, yet until recently there was no single staging system
      that could reliably predict survival, nor is there a universally accepted set of
      prognostic criteria for selecting a uniform group of patients. Response
      assessment has been limited by the inherent difficulties of reproducibly
      measuring pleural-based disease. The real impact of systemic chemotherapy on the
      natural history of malignant mesothelioma is still uncertain because phase III
      trials comparing chemotherapy with best supportive care have not yet been
      completed. Although nearly every class of cytotoxic agent has been evaluated in
      mesothelioma, response rates of greater than 20% have not been consistently
      demonstrated for any drug. The most active drug classes are the antifolates, the
      anthracyclines, and the platinums. Doxorubicin has historically been considered
      the gold-standard chemotherapy, although its true response rate is likely only
      15%. The most active commercially available drug for mesothelioma so far appears
      to be gemcitabine. Although gemcitabine has a limited role as a single agent, it
      is quite active in combination with a platinating agent. The impressive 48%
      response rate reported for the combination of gemcitabine with cisplatin in a
      single phase II study has made this regimen the new standard of care for off
      protocol treatment of this disease, although this trial still requires
      validation. With the recent introduction of several new agents with definite
      activity in this disease, the therapeutic nihilism previously associated with
      malignant pleural mesothelioma is gradually being replaced by a cautious
      optimism. Early trials of angiogenesis inhibitors, gene therapy, and vaccines
      offer additional avenues for treatment. As we begin to incorporate these active
      new drugs with each other and in adjuvant and neoadjuvant treatment regimens,
      there is reason to believe that superior results for patients with malignant
      pleural mesothelioma can be achieved in the near future.

PMID- 12057159
TI  - Recurrent or persistent thyroid cancer of follicular cell origin.
AB  - Most patients with differentiated thyroid cancer of follicular cell origin have a
      favorable postoperative course, and their prognosis often appears to be unrelated
      to the extent of initial surgical treatment in some studies. Important questions
      that need to be addressed include whether the extent of the initial operation has
      any impact on the subsequent tumor-free survival and total survival, and whether
      patients with persistent or recurrent disease benefit from reoperation.

PMID- 12057158
TI  - Papillary thyroid cancer.
AB  - Papillary thyroid cancer is the most common neoplasm of the thyroid gland.
      Surgical resection is the cornerstone of therapy. There is controversy regarding
      the extent of resection, ranging from thyroid lobectomy plus isthmusectomy to
      total thyroidectomy, but in experienced hands total thyroidectomy has many
      significant advantages over a lesser operation. Nonoperative therapy has no role
      as primary therapy for papillary thyroid cancer, but can be used in conjunction
      with surgery to improve outcome. Radioiodine in patients who have received total
      thyroidectomy can be used to identify residual occult tumor, recurrence, and
      metastasis, and can also be used to ablate the neoplasm, resulting in a
      substantial cure rate. Thyroid hormone is needed as replacement after total
      thyroidectomy, but can also be given as thyroid-stimulating hormone suppression,
      which may have an adjunctive benefit after resection.

PMID- 12057160
TI  - Anaplastic thyroid carcinoma.
AB  - Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive tumor
      characterized by rapid growth that causes death soon after diagnosis. Optimal
      treatment is debatable because of inherent difficulties investigating a rare
      malignancy associated with a survival of only months. Nevertheless, there is
      evidence that a multimodality approach consisting of surgery, chemotherapy, and
      radiotherapy is the preferred approach when the disease is localized. Eradication
      by complete surgical resection with total thyroidectomy, although often not
      feasible, followed or preceded by concurrent doxorubicin-based chemotherapy and
      hyperfractionated external beam radiation has been occasionally used and can
      rarely be associated with long-term survival. Surgical extirpation with radical
      organ resection is associated with high morbidity, and, although an aggressive
      surgical approach is reasonable in selected patients, organ preservation should
      be the goal in a disease with high recurrence and death rates. Any modality used
      in isolation usually fails to control local and regional ATC. In otherwise
      healthy patients who can tolerate aggressive therapy, chemoradiation and surgery
      may also be warranted for palliating incurable disease in the neck, which can
      cause death by asphyxiation.

PMID- 12057161
TI  - Medullary thyroid cancer.
AB  - Patients with clinically evident medullary thyroid cancer should have a total
      extracapsular thyroidectomy with bilateral central neck dissection and an
      ipsilateral prophylactic or therapeutic modified (functional) radical neck
      dissection when the primary tumor is greater than 1 cm and when the central neck
      nodes are positive. A prophylactic contralateral neck dissection should be done
      when the primary tumor is bilateral and when there is extensive lymphadenopathy
      on the side of the primary tumor. Patients who have gross, unresectable residual
      medullary thyroid cancer should receive postoperative external radiotherapy.
      Patients who are carriers of germ-line RET proto-oncogene point mutations or have
      an elevated (basal or stimulated) calcitonin levels on screening should have a
      prophylactic total thyroidectomy before age 6 years. In patients with an elevated
      basal or stimulated plasma calcitonin level and an intrathyroidal nodule on
      ultrasound, a total thyroidectomy and central neck lymph node dissection should
      be done. Patients with persistent or recurrent medullary thyroid cancer should
      have a complete thyroidectomy (if not done initially) and bilateral central and
      modified radical neck dissection, including upper mediastinal lymphadenectomy.
      Patients who are symptomatic from distant medullary thyroid cancer metastases
      (diarrhea, flushing, weight loss, or bone pain) should be treated with
      somatostatin analogs. Bone metastases should be resected if possible, and
      symptomatic lesions that are unresectable should be treated with external
      radiotherapy. Cytoreductive procedures such as radiofrequency ablation or
      cryoablation for liver metastases should be considered in symptomatic patients to
      reduce tumor burden. Localized pulmonary metastases should be resected.
      Chemotherapy or radioactive immunotherapy (iodine 131 labeled carcinoembryonic
      antigen monoclonal antibody) protocols should be considered in patients with
      nonoperative widely metastatic progressing medullary thyroid cancer.

PMID- 12057162
TI  - In situ breast cancer.
AB  - The clinical expression of in situ cancer varies widely but is usually occult.
      Diagnosis can be made by a variety of minimally invasive techniques. Treatment of
      lobular carcinoma in situ (LCIS) is patient-directed but generally requires only
      close follow-up. Mastectomy is the gold standard for ductal carcinoma in situ
      (DCIS) and is associated with low recurrence rates. Breast conservation therapy
      (BCT) has become an acceptable alternative. This choice of definitive therapy for
      DCIS depends largely on the ability to obtain negative margins. Any attempt at
      BCT should be coupled with the caveat of close postoperative long-term follow-up.
      Patients diagnosed with LCIS or who have a history of DCIS should be given the
      options for the use of tamoxifen for the reduction of subsequent development of
      invasive breast cancer. Risk versus benefits should be clearly defined.

PMID- 12057163
TI  - Early operable breast cancer.
AB  - Early operable breast cancer is a potentially curable disease. However, a
      substantial number of patients are at risk for systemic recurrence and death.
      Breast conservation therapy (BCT) should be considered the preferred surgical
      option for most women with early operable breast cancer. Adjuvant systemic
      chemotherapy or hormonal therapy can substantially reduce, although not
      eliminate, the risk of recurrence and death. Neoadjuvant or primary systemic
      therapy (PST) in operable breast cancer slightly increases the number of women
      treated with breast conservation versus mastectomy. Although PST may identify
      women who are likely to have a better prognosis (those with a pathologic complete
      response), current PST strategies do not offer a survival advantage over standard
      adjuvant approaches. Early results of high-dose chemotherapy trials thus far have
      not shown any advantage over conventional dose therapy in high-risk patients with
      10 or more positive lymph nodes. The role of adjuvant radiation therapy after
      mastectomy for all patients with high-risk early operable breast cancer is not
      fully defined.

PMID- 12057164
TI  - Carcinoma of the male breast.
AB  - Male breast cancer accounts for less than 1% of all breast cancers in the United
      States. The low incidence of this disease prevents therapeutic questions from
      being addressed in prospective randomized trials. As such, treatment algorithms
      have generally been extrapolated from those used in female breast cancer. Similar
      to female breast cancer, lymph node involvement and the size of the primary tumor
      are the most important factors in predicting disease-free and overall survival.
      Modified radical mastectomy remains the standard local therapeutic approach, with
      radiation therapy indicated for patients who have clinicopathologic features
      associated with a high risk for postmastectomy chest wall or lymph node
      recurrence. Similar to female breast cancer, adjuvant chemotherapy or hormonal
      therapy is indicated in the majority of men with breast cancer, specifically
      those with tumors larger than 1 cm or those with lymph node-positive disease.

PMID- 12057165
TI  - Locally advanced breast cancer.
AB  - Over the past 20 years, the prognosis for women diagnosed with locally advanced
      breast cancer (LABC; clinical stages IIB through IIIB) has improved significantly
      with recognition of the efficacy of multimodal therapy for reducing both local
      and distant recurrences, even in patients with inflammatory breast cancer (IBC).
      Most patients will respond to induction, or neoadjuvant, chemotherapy (NAC) with
      an anthracycline-based regimen, enabling many patients with large but operable
      tumors to undergo breast-conserving surgery (BCS) and enabling resection in most
      patients with inoperable disease. However, only a small percentage of patients
      achieve a pathologic complete response (CR) with this approach. Long-term disease
      free survival (DFS) and overall survival (OS) correlate with the extent of
      residual disease in the breast and axillary nodes following NAC. The addition of
      paclitaxel or docetaxel, either in combination with an anthracycline or as a
      separate regimen administered before or after anthracycline-based therapy,
      increases clinical and pathologic response rates and may improve DFS. With the
      possible exception of patients with IBC, BCS does not compromise outcome. Partial
      mastectomy should be accompanied by standard nodal dissection in patients with
      clinically or radiographically positive axillae; in patients with negative
      axillae, sentinel lymph node (SLN) sampling, with subsequent axillary dissection
      reserved for patients with involved nodes, may reduce postoperative morbidity.
      Patients who received only anthracycline-based NAC who are found to have
      significant residual disease in the breast or involved axillary nodes at surgery
      should receive adjuvant chemotherapy with paclitaxel. Postoperative radiation to
      the residual breast or chest wall and regional nodal areas reduces locoregional
      recurrences, but its impact on OS remains controversial. Adjuvant hormonal
      therapy with tamoxifen improves DFS and OS in patients with hormone receptor (HR)
      positive tumors, and ovarian ablation should be considered in premenopausal
      patients with HR-positive tumors and multiple involved nodes or stage IIIB
      disease. Neoadjuvant hormonal therapy with either tamoxifen or an aromatase
      inhibitor may benefit frail or elderly patients with HR-positive tumors for whom
      chemotherapy is not an option. No advantage has been demonstrated for high-dose
      chemotherapy requiring hematopoietic stem-cell support as either NAC or adjuvant
      therapy in LABC. Newer treatment approaches, including trastuzumab (Herceptin,
      Genentech, Inc., South San Francisco, CA), in patients with Her-2-overexpressing
      tumors or other biologic agents, do not have a proven role in the management of
      LABC at this time.

PMID- 12057166
TI  - Breast cancer during pregnancy.
AB  - The concurrent diagnosis of breast cancer and pregnancy is a challenging clinical
      situation that historically has placed the welfare of the mother in conflict with
      that of the fetus. Modified radical mastectomy, the preferred surgical option in
      women with breast cancer during pregnancy, can be accomplished with minimal fetal
      risk. Although breast-conserving surgery (lumpectomy or quadrantectomy) can be
      performed, the radiation therapy required to complete local therapy for the
      breast must be delayed until after delivery because of the risks associated with
      fetal exposure to radiation. Although much of the literature on the pharmacologic
      treatment of breast cancer during pregnancy is anecdotal, recently published data
      from our institution support the premise that breast cancer can be treated safely
      during the second and third trimesters of pregnancy with combination chemotherapy
      consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC).
      Therapeutic abortion does not appear to improve survival for the mother, but it
      may be an option if maternal health is jeopardized or fetal anomalies are seen or
      suspected.

PMID- 12057167
TI  - Ewing's sarcoma.
AB  - Patients with Ewing's sarcoma should be transferred to a comprehensive cancer
      center for evaluation and management when the diagnosis is suspected. Proper
      biopsy technique is essential to preserve all therapeutic options, including limb
      preservation surgery. In addition to conventional histologic examination, biopsy
      tissue must be obtained for molecular biology studies. Demonstration of the
      consistent chromosomal translocation associated with Ewing's sarcoma is essential
      for diagnosis, and the specific type of fusion transcript has prognostic
      implications. Treatment must be intimately coordinated among oncologist, surgeon,
      and radiation oncologist. Successful treatment requires systemic, multi-agent
      chemotherapy and local control. The primary tumor can be treated with surgery,
      radiation therapy, or a combination of the two. The choice of modality should be
      dictated by the age of the patient, location of the primary tumor, functional
      consequences of the intervention, and concern about late effects, especially
      secondary malignancy. Treatment of the patient who presents with clinically
      detectable metastatic disease or who relapses after initial therapy remains
      unsatisfactory and controversial.

PMID- 12057168
TI  - Radiation-induced sarcoma.
AB  - Radiation-induced sarcomas can originate in either the irradiated bone or soft
      tissues. Most of these tumors are high-grade. The most common histologic subtypes
      are malignant fibrous histiocytoma (MFH) and osteosarcoma, although other
      histologies (eg, angiosarcoma, rhabdomyosarcoma) can occur. Tumor size and grade
      are the two most important prognostic factors for soft tissue sarcomas, including
      those associated with radiation therapy. The therapy is therefore dictated by the
      risk of distant metastases. High-grade tumors that are larger than 5 cm should be
      treated with primary chemotherapy followed by a margin-negative surgical excision
      of the residual disease. All low-grade tumors and high-grade tumors 5 cm or
      smaller should be treated with a margin-negative surgical excision, and systemic
      chemotherapy should be considered when a negative margin is difficult or
      impossible to accomplish. Radiation-induced sarcomas (either MFH or osteosarcoma)
      originating in bone should be approached with primary chemotherapy followed by a
      margin-negative excision similar to de novo bone sarcomas. The dose-intensity of
      the active agents should be adjusted appropriately for the age, performance
      status, and prior therapy in a given patient.

PMID- 12057169
TI  - Desmoid tumors.
AB  - Because of the wide variety of anatomic locations and patient factors, there is
      no one treatment that is appropriate for all desmoid tumors. The type of
      treatment depends on tumor characteristics and location, as well as patient
      characteristics and preferences. Desmoid tumors can be persistent and frustrating
      to manage because no one treatment modality offers a high likelihood of
      remission. Multiple modalities may be necessary in some patients. Although
      mortality is rare and is usually due to local complications, significant
      disability or morbidity can result from desmoid tumors, their treatment, and
      complications arising from treatment. The entire clinical picture and the
      patient's preferences must be taken into account when deciding on an appropriate
      treatment plan. Patients with desmoid tumors are optimally managed in a
      multidisciplinary setting with close collaboration between surgeon, pathologist,
      diagnostic radiologist, radiation oncologist, and medical oncologist. When
      possible, surgical resection with negative margins is the preferred modality.
      When surgical resection with negative margins may prove disabling, surgery can be
      followed by postoperative radiation, although the role and efficacy of this are
      controversial. In locations where surgical extirpation is difficult or
      unfeasible, primary radiation, hormonal therapy, or chemotherapy should be
      considered. Familiar adenosis polyposis (FAP)-associated mesenteric lesions,
      sporadic tumors present without change for months or years, or tumors present in
      areas where progression will not present significant additional morbidity are
      candidates for observation only.

PMID- 12057170
TI  - Gastrointestinal stromal tumors.
AB  - The nonepithelial, nonlymphoid tumors of the gastrointestinal tract are
      heterogeneous in terms of clinical presentation, behavior, pathology, and genetic
      features. Concepts regarding these tumors have changed rapidly over the past
      decade as nomenclature has evolved. Many of these tumors have no muscle
      differentiation, and designations such as leiomyoma or leiomyosarcoma are
      inappropriate for many of these neoplasms. With an improved understanding of the
      biology of these tumors, gastrointestinal stromal tumor (GIST) is used as a
      specific term for tumors of the gastrointestinal tract that lack markers of
      myogenic differentiation, but stain positive for vimentin, and express CD34 and
      CD117, the product of the c-kit oncogene. Both benign and malignant types are
      recognized. In addition to myogenic tumors and GIST, gastrointestinal autonomic
      nerve tumors (GANT) are also recognized. Complete en bloc surgical resection,
      when possible, is the cornerstone of therapy. Metastasis tends to occur to the
      liver and within the peritoneal cavity, especially in patients whose tumors have
      ruptured spontaneously or been violated by the surgeon. Incomplete surgical
      resection and metastatic disease indicate a dismal prognosis in the majority of
      patients. Recurrent or metastatic disease is often resected, but this has an
      uncertain impact on outcome. Operation may palliate patients with intestinal
      obstruction or other symptoms. For patients with unresectable disease, the
      results with systemic chemotherapy have been dismal. Treatment with
      doxorubicin/ifosfamide combinations is of dubious value. Hepatic arterial
      embolization, with and without intra-arterial chemotherapy, results in regression
      of liver metastases in selected patients. Regression has also been seen using
      intrahepatic arterial infusion of doxorubicin without embolization. The impact of
      such treatment on outcome, however, is poorly studied. Aggressive surgical
      resection of peritoneal metastases with intraperitoneal chemotherapy has been
      advocated, but requires formal study in large trials.

PMID- 12057171
TI  - Retroperitoneal sarcomas.
AB  - The approach to the management of retroperitoneal tumors begins with a complete
      history and physical examination. Imaging of the abdomen and pelvis by computed
      tomography (CT) provides both an imaging modality and a method by which to obtain
      tissue for diagnosis. Because a histologic diagnosis is essential in treatment
      planning, adequate tissue can usually be obtained by a CT-guided core biopsy. If
      the diagnosis is sarcoma, additional tests necessary for staging include plain
      chest radiography and evaluation of the liver by either CT scan or magnetic
      resonance imaging (MRI). The treatment options for primary retroperitoneal
      sarcomas include chemotherapy, radiation therapy, surgery, or a combination of
      these modalities; therefore, a multidisciplinary group best manages treatment
      planning. Primary radiation therapy for cure is seldom effective for
      retroperitoneal sarcomas but can provide palliation in select cases. Systemic
      chemotherapy for chemosensitive lesions, such as poorly differentiated
      liposarcoma, malignant fibrous histiocytoma (MFH), synovial cell sarcoma, and
      primitive neuroectodermal tumors (PNET), can be useful when used in a neoadjuvant
      manner. Consequently, surgical resection continues to be the mainstay of
      treatment for retroperitoneal sarcomas and requires en bloc resection of the
      primary tumor. Frequently this includes adjacent organs such as colon, small
      bowel, kidney, adrenal, and pancreas. Postoperative adjuvant therapy with
      chemotherapy or radiation has not been proven to be of any additional benefit.
      Overall treatment results are predominantly influenced by tumor stage, grade,
      size, and margins of surgical resection. Follow-up CT scans at 6-month intervals
      and surgical resection of recurrences can be valuable.

PMID- 12057172
TI  - Mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin's lymphoma that is
      incurable with current chemotherapeutic approaches. Despite response rates of 50%
      to 70% to many regimens, all patients have disease progression after
      chemotherapy, and median survival is approximately 3 years. There is no clear
      standard of care for MCL, which increases the importance of enrolling patients in
      clinical trials. Off protocol, chemotherapy with chlorambucil or combination
      regimens can be used in patients who are not candidates for high-dose therapy.
      Autologous stem cell transplant as initial therapy has high response rates and
      prolongs time to progression but has not been shown to improve survival. For
      young patients with matched donors, allogeneic transplant appears promising in
      the limited numbers of patients treated to date. Other agents, including
      rituximab, fludarabine, and cladribine, have demonstrated activity but do not
      appear to offer survival advantages over combination chemotherapy.

PMID- 12057173
TI  - [Public health, politics and administration: hostages or accomplices?].

PMID- 12057174
TI  - [Endocrine disruptors: a very personal story with multiple personalities].

PMID- 12057175
TI  - [What Gaceta Sanitaria does for you and what you can do for Gaceta Sanitaria].

PMID- 12057177
TI  - [Description of psychosocial risk factors in four companies].
AB  - OBJECTIVE: To describe the distribution of work-related psychosocial risk factor
      scores in four companies according to the personal and occupational
      characteristics of the workers. METHODS: Cross-sectional study of a sample of 890
      workers in four companies who participated in this study voluntarily. The overall
      response rate was 34.5%. A self-administrated questionnaire was used to measure
      the presence of demand, control and social support according to the workers'
      perceptions. Statistical analyses were performed using median and dispersion
      measures of psychosocial risk factors for each company separately, as well as
      description of their distribution according to personal and occupational
      variables. RESULTS: The median score for social support was almost always equal
      to 5 for all four companies. However, there was greater variability in
      psychological demand (between 13 and 16), and for control (between 20 and 26).
      Comparison of the scores for social and occupational variables revealed similar
      values for social support but not for control and demand, which showed greater
      variation according to sex (men), age group (less than 40 years) and occupation
      (clerks). CONCLUSIONS: Although the low response rate could limit the validity of
      our results, this is the first study to value the distribution of work-related
      psychosocial risk factor scores in four companies in Spain. Variability among
      companies for different groups of workers was found. This study could be useful
      for future studies exploring the feasibility of defining reference values for use
      in preventive measures.

PMID- 12057176
TI  - [Sociodemographic differences in adherence to the Mediterranean dietary pattern
      in Spanish populations].
AB  - OBJECTIVES: Lower social classes tend to eat a less healthy diet. The aim of this
      study was to compare adherence to the Mediterranean dietary pattern among
      different demographic and social groups in the adult population. METHODS: A cross
      sectional study was performed in southern and northern regions of Spain in
      healthy volunteers (15,634 men and 25,812 women), aged 29-69 years, who were
      members of the European Prospective Investigation on Cancer cohort in Spain. Nine
      groups of food were included in the definition of the Mediterranean diet:
      vegetables and garden products, fruits, pulses, cereals, red meat, fish, olive
      oil, milk and milk products, and wine. Two techniques were used in the analysis:
      comparison of the mean daily intake of each group and calculation of an overall
      score for all the foods according to educational level and original social class.
      RESULTS: Groups with the lowest educational levels consumed more cereals and
      pulses and lower quantities of vegetables, olive oil (women), milk and milk
      products (men). Wine consumption was positively associated with education in
      women and was negatively associated in men. Calculation of a score to measure
      overall adherence to the Mediterranean dietary pattern eliminated differences
      according to each food category. No variations were found according to
      educational level, but small differences were found in original social class. The
      adherence score was lowest in young adults and women and was slightly higher in
      the south than in the north of Spain. CONCLUSIONS: The results suggest that the
      Mediterranean dietary pattern is fairly uniform, at least in the adult population
      of the regions included in this study.

PMID- 12057178
TI  - [Study of non-participation in the breast cancer screening program in the city of
      Valencia (Spain)].
AB  - AIM: To determine the reasons for non-participation of women in a breast cancer
      screening program. METHODS: We performed an observational, cross-sectional study
      in women who were invited to participate in the breast cancer screening program
      in the city of Valencia and who failed to attend. The women were interviewed in
      their homes through a questionnaire consisting of 25 questions grouped as
      follows: knowledge of the program, reasons for nonparticipation, attitudes or
      beliefs and characteristics of the interviewees (socioeconomic and educational
      variables and age). A descriptive analysis was performed. Differences in the
      characteristics of women were evaluated through bivariate analysis. Multivariate
      analysis was performed through logistic regression. RESULTS: A total of 783
      addresses were used, 411 questionnaires were completed and 361 were analyzed. The
      50 questionnaires used in the pilot study were excluded because, as a consequence
      of this study, the questionnaire had been modified. Most of the women (93.4%)
      (CI: 90.3-95.7) remembered having an appointment. The main reason for not
      attending was being screened in another health service in 48.8% (CI: 43.6-53.9),
      followed by various personal reasons in 16.1% (CI: 12.3-19.9) and inability to
      keep the appointment at the specified time in 15.5% (CI: 11.8-19.2). Comparison
      of women in the middle and upper social classes with those in the lower classes
      revealed important differences. Middle and upper class women had a higher
      probability of knowing about the program and of being on hormone replacement
      therapy (HRT) and the most frequent reason for non-attendance was attendance at
      another program run by another health service. In lower class women the reasons
      for non-attendance were fear, not believing the program to be important to health
      and inability to keep the appointment at the specified time. In the multivariate
      analysis, the variables that entered the model were HRT, social class and
      education. Thus, middle or upper class women undergoing HRT and with secondary or
      higher education had a higher probability of being screened. CONCLUSIONS: The
      profile of non-participating women belongs on the one hand to those in the middle
      or upper social classes, undergoing HRT and being screened by other health
      services and, on the other, to a group of women of low social class, whose reason
      for non-participation is fear and timetable difficulties.

PMID- 12057179
TI  - [Pesticide application practices in agricultural workers].
AB  - OBJECTIVE: We describe the sociodemographic characteristics and determinants of
      pesticide exposure in agricultural workers applying pesticides. METHODS: The
      workers selected were included in a case-control study carried out in the
      Autonomous Community of Valencia in Spain. Contact was made by telephone and
      individuals who had been involved in agricultural work during the relevant period
      of exposure were interviewed face-to-face to gain information on the following
      determinants of pesticide exposure: crops and periods worked, mixing of products,
      treatment equipment, participation in the washing of equipment, use of personal
      protection during the treatments and knowledge of the risks of pesticide
      exposure. RESULTS: Eighty-nine workers, aged between 16 and 46 years old, were
      included. Most of the interviewees had primary education or less. Pesticide
      treatments were mostly applied on high crops (82%), with manual equipment (61%)
      and throughout the year (45%). Workers frequently performed tasks involving
      additional exposure to pesticides (mixing chemicals, 66%, or washing equipment,
      60%). Sixty-five percent of the workers used no personal protection or used it
      defectively. No differences were found in personal protection use according to
      age, family income or education. Most of the workers (90%) reported knowledge of
      the health risks of pesticide exposure and 21% of them rated the risk as null.
      CONCLUSIONS: Workers involved in pesticide application use personal protection
      measures very defectively. There is a clear need to develop specific prevention
      programs for these workers. The determinants of pesticide exposure in
      agricultural workers described in this study should be properly assessed in
      epidemiological studies of the health effects of pesticides on agricultural
      workers.

PMID- 12057180
TI  - [Halogenated by-products of chlorination in tap water].
AB  - OBJECTIVE: The presence of trihalomethanes in the water systems of several
      Spanish cities has been demonstrated. The aim of this study was to analyze
      trihalomethane concentrations in the water provided for human consumption in the
      city of Barcelona. METHODS: We analyzed 151 water samples collected in 1998. The
      analyses were performed in the Public Health Laboratory of Barcelona using the
      purge-and-trap method and subsequent determination by gas chromatography and mass
      spectrometry. The results are presented according to the source of the water: the
      rivers of Llobregat or Ter, or a mixture of these. RESULTS: Trihalomethane
      concentrations in the water from Ter were relatively low, with a predominance of
      chloroform and bromodichloromethane, while concentrations in the water from
      Llobregat were much higher, with a predominance of bromoform and
      dibromochloromethane. Mixed water showed intermediate concentrations. The total
      concentrations reached in the water from Llobregat were above 100 microg/l.
      CONCLUSIONS: The results show the need to continue reducing organic pollution and
      halogenated compounds in the water used for human consumption in Barcelona.

PMID- 12057181
TI  - [Quality of manuscript evaluation in Gaceta Sanitaria].
AB  - OBJECTIVE: To describe strengths and weaknesses of peer reviews of manuscripts
      received in Gaceta Sanitaria in order to guide reviewers selection, to improve
      quality of peer reviews and to establish an internal system to be incorporated to
      the editorial process of handling manuscripts. METHODS: 100 peer reviews of 55
      manuscripts received during 2000 and 2001 were included. A questionnaire
      containing closed questions assessing specific and general components of reviews'
      quality was applied (answers Yes/No or on a 5-points scale). Descriptive and
      correlation analyses were performed for the different items in the questionnaire.
      An Index of Quality was obtained by adding the ratings on the items in the
      questionnaire measuring specific quality components. RESULTS: Peer reviews were
      rated high regarding completeness of the forms for reviewers (84%),
      constructiveness of the comments (reviews over 3: 63%), identification of the
      strengths and weaknesses of the method (reviews over 3: 59%) and substantiation
      of the reviewer comments (reviews over 3: 58%). Assessment of the manuscript's
      relevance (reviews over 3: 40%) or originality (reviews over 3: 35%) were less
      frequent. CONCLUSIONS: Quality of peer reviews in Gaceta Sanitaria is good. Some
      weaknesses in the reviews have been pointed out. It is possible to establish a
      systematic process for assessing peer reviewers using simple indicators such as
      general utility of the review for the editorial decision and general quality of
      the review.

PMID- 12057182
TI  - [Perspectives on endocrine disruption].
AB  - Two decades ago, reports of alterations in the reproductive function of some wild
      animal species and clear evidence of human and animal exposure to chemical
      substances with hormonal activity agonist and antagonist generated what is known
      now as the hypothesis of endocrine disruption. This is an emerging environmental
      health problem that has challenged some of the paradigms on which the control and
      regulation of the use of chemical compounds is based. The need to include in
      routine toxicology tests new research objectives that specifically refer to the
      development and growth of species and to the homeostasis and functionality of
      hormonal systems, has served to complicate both the evaluation of new compounds
      and the re-evaluation of existing ones. The repercussions on regulation and
      international trade have not taken long to be felt. On both sides of the
      Atlantic, screening systems for endocrine disrupters have been designed and
      established, and research programmes have been launched to characterise and
      quantify adverse effects on human and animal health and to develop preventive
      measures.

PMID- 12057183
TI  - [Concentrations of persistent toxic compounds in the Spanish population: a puzzle
      without pieces and the protection of public health].
AB  - The contamination by persistent toxic compounds (PTCs) of the general population
      is a fact of relevance from a public health perspective. It is also relevant to
      health care professionals, as well as for environmental, food, industrial and
      economic policies. Though in Spain information on food contamination by PTCs
      shows large time and geographic gaps, the scarcity of data is even more severe on
      the concentrations that PTCs have in people: a representative study of a general
      healthy population living in a wide geographic area has never been conducted in
      the country. However, the available studies indicate that around 80-100% of the
      population has detectable concentrations of DDE, PCBs, hexachlorbenzene or
      lindane. Studies on the effects that PTCs have upon humans are extremely
      infrequent in Spain. Yet, the international literature suggests that some PTCs
      may induce significant biological and clinical effects at doses below those
      traditionally deemed "safe". The mechanism of action of PTCs are not restricted
      to endocrine disruption. Assessing the clinical and social relevance of the more
      subtle and long-term effects of PTCs presents interesting challenges and
      opportunities. Spain and other European countries lack population indicators on
      the impact that environmental processes have on human health. Several government
      levels have a role to fulfill in the monitoring of biological levels of PTCs
      among persons in order to assess the risks of adverse health effects. Along with
      over a hundred other countries. Spain will soon try to implement the Stockholm
      treaty on persistent organic pollutants (POPs). This constitutes a new
      opportunity to develop more efficient policies to control PTC residues in food,
      humans and the environment. As part of the treaty implementation it is necessary
      to launch a Report on factors that influence body concentrations of PTCs in the
      Spain general population.

PMID- 12057184
TI  - [Some methodological aspects of age-period-cohort models. Application to cancer
      mortality trends].
AB  - Age-period-cohort models are usually used in descriptive epidemiological studies
      to analyze time trends in incidence or mortality. The exact linear relationship
      between the three effects of these models has the effect of making the parameters
      of the full model impossible to estimate, which is called non-identifiability. In
      these notes two of the most frequently used methods to analyze age-period-cohort
      models will be explained. One is based on penalty functions and the other on
      estimable functions (drift and curvatures or deviation from linearity). Both
      methods will be illustrated with two examples in which temporal trends of breast
      and lung cancer mortality in women from Catalonia in Spain will be studied. These
      examples show how the methods based on penalty functions tend to attribute the
      trend exclusively to a cohort effect. Consequently, the use of methods based on
      estimate functions is recommended.

PMID- 12057185
TI  - [The dubious relationship between peer-review and quality].

PMID- 12057187
TI  - [Could the "botellon" be considered to be a public health problem or a public
      order matter?].

PMID- 12057188
TI  - HtrA--a renaissance protein.
AB  - Initially identified as proteases, members of the HtrA/DegP family of proteins
      have also been shown to act as chaperones in bacteria, and more recently
      implicated, as regulators of apoptosis in mammals. Two new structures of
      mammalian HtrA2 and E. coli DegP provide insights into the origin of this
      plurality of function.

PMID- 12057189
TI  - The structure of the C-cadherin ectodomain resolved.
AB  - In a recent issue of Science, Boggon et al. report the structure of the full
      length C-cadherin ectodomain (CCAD1-5). Previous cell adhesion and direct force
      measurements demonstrated that the CCAD1-5 ectodomain is a functionally active
      adhesion molecule, and thus the determination of its structure is a significant
      achievement.

PMID- 12057190
TI  - Bridging the gap between SCF and ubiquitin transfer.
AB  - The first crystal structure of a core SCF complex has been determined to 3.2 A.
      Together with previous data obtained for RING E3-E2 and Skp1-Skp2 adaptor
      complexes, the structure provides substantial insight into SCF-mediated protein
      modification by ubiquitin, a process that regulates protein modification and
      degradation in systems ranging from cell cycle progression to transcription.

PMID- 12057191
TI  - Crystal structure of the C-terminal WD40 repeat domain of the human Groucho/TLE1
      transcriptional corepressor.
AB  - Groucho (Gro)/TLE proteins are transcriptional corepressors that lack inherent
      DNA binding but interact with DNA-bound transcription factors and histones, and
      recruit histone deacetylases. Groucho-mediated repression is essential in
      embryonic development and involved in regulation of Wnt signaling in adult
      tissue. We have determined the 1.6 A crystal structure of a C-terminal fragment
      of human Groucho/TLE1, comprising part of the Ser/Pro-rich region and a seven
      bladed beta propeller WD40 repeat domain, implicated in protein-protein
      interactions. The structure confirms the relationship to the yeast Tup1
      corepressor, but reveals important structural differences specific to the
      metazoan system. Analysis of missense mutations in the C. elegans Groucho homolog
      UNC-37 identifies sites of interaction with repression effectors, and suggests an
      induced fit binding site for eh1 domains of Engrailed-type transcription factors.

PMID- 12057192
TI  - Intra- and intermolecular interactions in sucrose transporters at the plasma
      membrane detected by the split-ubiquitin system and functional assays.
AB  - Interaction of two separately expressed halves of sucrose transporter SUT1 was
      detected by an optimized split-ubiquitin system. The halves reconstitute sucrose
      transport activity at the plasma membrane with affinities similar to the intact
      protein. The halves do not function independently, and an intact central loop is
      not required for membrane insertion, plasma membrane targeting, and transport.
      Under native conditions, the halves associate into higher molecular mass
      complexes. Furthermore, the N-terminal half of the low-affinity SUT2 interacts
      functionally with the C-terminal half of SUT1. Since the N terminus of SUT2
      determines affinity for sucrose, the reconstituted chimera has lower affinity
      than SUT1. The split-ubiquitin system efficiently detects intramolecular
      interactions in membrane proteins, and can be used to dissect transporter
      structure.

PMID- 12057193
TI  - Variation on a theme of SDR. dTDP-6-deoxy-L- lyxo-4-hexulose reductase (RmlD)
      shows a new Mg2+-dependent dimerization mode.
AB  - dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD) catalyzes the final step in the
      conversion of dTDP-D-glucose to dTDP-L-rhamnose in an NAD(P)H- and Mg2+-dependent
      reaction. L-rhamnose biosynthesis is an antibacterial target. The structure of
      RmlD from Salmonella enterica serovar Typhimurium has been determined, and
      complexes with NADH, NADPH, and dTDP-L-rhamnose are reported. RmlD differs from
      other short chain dehydrogenases in that it has a novel dimer interface that
      contains Mg2+. Enzyme catalysis involves hydride transfer from the nicotinamide
      ring of the cofactor to the C4'-carbonyl group of the substrate. The substrate is
      activated through protonation by a conserved tyrosine. NAD(P)H is bound in a
      solvent-exposed cleft, allowing facile replacement. We suggest a novel role for
      the conserved serine/threonine residue of the catalytic triad of SDR enzymes.

PMID- 12057194
TI  - Structure of the retinal determination protein Dachshund reveals a DNA binding
      motif.
AB  - The Dachshund proteins are essential components of a regulatory network
      controlling cell fate determination. They have been implicated in eye, limb,
      brain, and muscle development. These proteins cannot be assigned to any
      recognizable structural or functional class based on amino acid sequence
      analysis. The 1.65 A crystal structure of the most conserved domain of human
      DACHSHUND is reported here. The protein forms an alpha/beta structure containing
      a DNA binding motif similar to that found in the winged helix/forkhead subgroup
      of the helix-turn-helix family. This unexpected finding alters the previously
      proposed molecular models for the role of Dachshund in the eye determination
      pathway. Furthermore, it provides a rational framework for future mechanistic
      analyses of the Dachshund proteins in several developmental contexts.

PMID- 12057195
TI  - Accessory protein recruitment motifs in clathrin-mediated endocytosis.
AB  - Clathrin-mediated endocytosis depends upon the interaction of accessory proteins
      with the alpha-ear of the AP-2 adaptor. We present structural characterization of
      these regulatory interactions. DPF and DPW motif peptides derived from eps15 and
      epsin bind in type I beta turn conformations to a conserved pocket on the alpha
      ear platform. We show evidence for a second binding site that is DPW motif
      specific. The structure of a complex with an AP-2 binding segment from
      amphiphysin reveals a novel binding motif that we term FxDxF, which is engaged in
      an extended conformation by a unique surface of the platform domain. The FxDxF
      motif is also used by AP180 and the 170 kDa isoform of synaptojanin and can be
      found in several potential endocytic proteins, including HIP1, CD2AP, and PLAP. A
      mechanism of clathrin assembly regulation is suggested by three different AP-2
      engagement modes.

PMID- 12057196
TI  - The Ig-like structure of the C-terminal domain of lamin A/C, mutated in muscular
      dystrophies, cardiomyopathy, and partial lipodystrophy.
AB  - Lamins are nuclear intermediate filaments that, together with lamin-associated
      proteins, maintain nuclear shape and provide a structural support for chromosomes
      and replicating DNA. We have determined the solution structure of the human lamin
      A/C C-terminal globular domain which contains specific mutations causing four
      different heritable diseases. This domain encompasses residues 430-545 and adopts
      an Ig-like fold of type s. We have also characterized by NMR and circular
      dichroism the structure and thermostability of three mutants, R453W and R482W/Q,
      corresponding to "hot spots" causing Emery-Dreifuss muscular dystrophy and
      Dunnigan-type lipodystrophy, respectively. Our structure determination and mutant
      analyses clearly show that the consequences of the mutations causing muscle
      specific diseases or lipodystrophy are different at the molecular level.

PMID- 12057197
TI  - X-ray crystallographic studies on butyryl-ACP reveal flexibility of the structure
      around a putative acyl chain binding site.
AB  - Acyl carrier protein (ACP) is an essential cofactor in biosynthesis of fatty
      acids and many other reactions that require acyl transfer steps. We have
      determined the first crystal structures of an acylated form of ACP from E. coli,
      that of butyryl-ACP. Our analysis of the molecular surface of ACP reveals a
      plastic hydrophobic cavity in the vicinity of the phosphopantethylated Ser36
      residue that is expanded and occupied by the butyryl and beta-mercaptoethylamine
      moieties of the acylated 4'-phosphopantetheine group in one of our crystal forms.
      In the other form, the cavity is contracted, and we propose that the protein has
      adopted the conformation after delivery of substrate into the active site of a
      partner enzyme.

PMID- 12057199
TI  - Screening transthyretin amyloid fibril inhibitors: characterization of novel
      multiprotein, multiligand complexes by mass spectrometry.
AB  - Tetrameric transthyretin is involved in transport of thyroxine and, through its
      interactions with retinol binding protein, vitamin A. Dissociation of these
      structures is widely accepted as the first step in the formation of transthyretin
      amyloid fibrils. Using a mass spectrometric approach, we have examined a series
      of 18 ligands proposed as inhibitors of this process. The ligands were evaluated
      for their ability to bind to and stabilize the tetrameric structure, their
      cooperativity in binding, and their ability to compete with the natural ligand
      thyroxine. The observation of a novel ten-component complex containing six
      protein subunits, two vitamin molecules, and two synthetic ligands allows us to
      conclude that ligand binding does not inhibit association of transthyretin with
      holo retinol binding protein.

PMID- 12057198
TI  - Structure at 1.9 A resolution of a quinohemoprotein alcohol dehydrogenase from
      Pseudomonas putida HK5.
AB  - The type II quinohemoprotein alcohol dehydrogenase of Pseudomonas putida is a
      periplasmic enzyme that oxidizes substrate alcohols to the aldehyde and transfers
      electrons first to pyrroloquinoline quinone (PQQ) and then to an internal heme
      group. The 1.9 A resolution crystal structure reveals that the enzyme contains a
      large N-terminal eight-stranded beta propeller domain (approximately 60 kDa)
      similar to methanol dehydrogenase and a small C-terminal c-type cytochrome domain
      (approximately 10 kDa) similar to the cytochrome subunit of p-cresol
      methylhydoxylase. The PQQ is bound near the axis of the propeller domain about 14
      A from the heme. A molecule of acetone, the product of the oxidation of
      isopropanol present during crystallization, appears to be bound in the active
      site cavity.

PMID- 12057200
TI  - The 1.4 a crystal structure of kumamolysin: a thermostable serine-carboxyl-type
      proteinase.
AB  - Kumamolysin is a thermostable endopeptidase from Bacillus novosp. MN-32,
      exhibiting maximal proteolytic activity around pH 3. It belongs to the newly
      identified family of serine-carboxyl proteinases, which also includes CLN2, a
      human lysosomal homolog recently implicated in a fatal neurodegenerative disease.
      Kumamolysin and its complexes with two aldehyde inhibitors were crystallized, and
      their three-dimensional structures were solved and refined with X-ray data to 1.4
      A resolution. As its Pseudomonas homolog, kumamolysin exhibits a Ser/Glu/Asp
      catalytic triad with particularly short interconnecting hydrogen bonds and an
      oxyanion hole enabling the reactive serine to attack substrate peptide bonds at
      quite acidic pH. An additional Glu/Trp pair, unique to kumamolysin, might further
      facilitate proton delocalization during nucleophilic attack, in particular at
      high temperature.

PMID- 12057201
TI  - A hyperthermostable D-ribose-5-phosphate isomerase from Pyrococcus horikoshii
      characterization and three-dimensional structure.
AB  - A gene homologous to D-ribose-5-phosphate isomerase (EC 5.3.1.6) was found in the
      genome of Pyrococcus horikoshii. D-ribose-5-phosphate isomerase (PRI) is of
      particular metabolic importance since it catalyzes the interconversion between
      the ribose and ribulose forms involved in the pentose phosphate cycle and in the
      process of photosynthesis. The gene consisting of 687 bp was overexpressed in
      Escherichia coli, and the resulting enzyme showed activity at high temperatures
      with an optimum over 90 degrees C. The crystal structures of the enzyme, free and
      in complex with D-4-phosphoerythronic acid inhibitor, were determined. PRI is a
      tetramer in the crystal and in solution, and each monomer has a new fold
      consisting of two alpha/beta domains. The 3D structures and the characterization
      of different mutants indicate a direct or indirect catalytic role for the
      residues E107, D85, and K98.

PMID- 12057527
TI  - The forgotten female: Pediatric and adolescent gynecological concerns and their
      reproductive consequences.
AB  - Future reproductive performance is not often addressed in pediatric and
      adolescent gynecological conditions. This overview reviews conditions that
      present in childhood and adolescence and discusses what is known about the future
      fertility in these women. The following topics are selected: STD exposure,
      dysfunctional uterine bleeding, eating disorders, adolescent athletics,
      polycystic ovarian syndrome, premature ovarian failure, childhood cancer
      survivors, Mullerian duct anomalies, congenital adrenal hyperplasia, cystic
      fibrosis, and epilepsy.

PMID- 12057528
TI  - Overweight teens at increased risk for weight gain while using depot
      medroxyprogesterone acetate.
AB  - STUDY OBJECTIVE: To determine if factors such as body mass index (BMI), race, and
      age are associated with weight gain in adolescents receiving depot
      medroxyprogesterone acetate (DMPA). DESIGN/SETTING: Retrospective chart review at
      three rural health department family planning clinics and a university-based
      adolescent clinic in rural eastern North Carolina. PARTICIPANTS: Adolescent
      females, aged 12-19, who used either oral contraceptive pills (OCPs) or DMPA
      consistently for the first year of use. MAIN OUTCOME MEASURE: Weight change at
      one year. RESULTS: A total of 239 adolescent females were included in the
      analysis; 117 were DMPA users and 122 were OCP users. The mean weight gain for
      the DMPA group was 8.9 lbs. compared with 4.79 lbs. in the OCP group (P =.002).
      The change in BMI from baseline was greater among the DMPA group (1.51 +/- 1.94)
      than the OCP group (.75 +/- 1.65), P =.001. After adjusting for age, race, and
      contraceptive method, initial BMI was associated with weight gain (P =.009).
      CONCLUSIONS: Adolescent females using DMPA gained significantly more weight over
      one year than those girls using OCPs. Adolescent females who are overweight at
      the initiation of DMPA may be more likely to have significant weight gain during
      the first year of use.

PMID- 12057530
TI  - Limb pain associated with an undiagnosed hemoglobinopathy and pseudononcyesis.
AB  - Over a 2-month period, a 16-yr-old African-American female presented with
      recurrent episodes of severe, migratory limb pain. Sickle cell C disease was
      ultimately diagnosed. She adamantly denied sexual activity but was found to be 28
      weeks pregnant. Her limb pain was probably triggered by the metabolic and
      hemodynamic demands of pregnancy. The case illustrates the importance of
      thoroughly examining patients with recurrent, unexplained physical complaints.

PMID- 12057531
TI  - Knowledge, attitude, and behavior of secondary (high) school students concerning
      HIV/AIDS in Enugu, Nigeria, in the year 2000.
AB  - STUDY OBJECTIVE: To investigate the knowledge, attitude, and behavior of
      secondary (high) school students concerning HIV/AIDS as a way of assessing the
      need for inclusion of reproductive health education in the school curriculum.
      DESIGN: A questionnaire was constructed to expose depth of knowledge and attitude
      of respondents concerning HIV/AIDS. SETTING: This was a workshop venue, a civic
      center, outside a school compound. PARTICIPANTS: Three hundred and sixty students
      were randomly selected from 5 secondary (high) schools in Enugu, Nigeria.
      INTERVENTION: The questionnaire was administered just before the commencement of
      a workshop. MAIN OUTCOME MEASURE: All the students responded to the questionnaire
      but none responded to all the questions. RESULTS: The students had a defective
      knowledge of the disease. They were aware and afraid of the disease as being
      deadly but not sure of the cause, nature, or modes of transmission and
      prevention, except that illicit sexual activity should be avoided. Their attitude
      and behavior were consequently defective. Their main source of information was
      the media. CONCLUSION: There is need to provide students with correct, detailed,
      and broad-based information on reproductive health as part of the school
      curriculum to help them acquire adequate knowledge and develop appropriate
      attitude and behavior towards HIV/AIDS and other STDs.

PMID- 12057529
TI  - Douching behavior in high-risk adolescents. What do they use, when and why do
      they douche?
AB  - OBJECTIVES: To describe feminine hygiene practices and douching behavior in
      adolescent women. DESIGN: A cross-sectional anonymous survey. SUBJECTS:
      Adolescents (majority rural) admitted to a correctional institution for girls.
      MAIN OUTCOME MEASURES: Description of feminine hygiene practices, prevalence of
      vaginal douching, types of substances used, reported reasons for, and timing of
      douching. RESULTS: In a period of 16 weeks, 104 girls were surveyed within a week
      of admission. The mean age was 15.4 (SD 1.5; range 12-18) yr, and age at sexual
      debut 13.1 (SD 1.4) yr. Use of feminine hygiene products was reported by: 9% for
      feminine suppository, 33% towelettes, 40% spray, 67% feminine wash; only 18%
      reported no use of those feminine hygiene products listed. A history of ever
      having douched was reported by 79%; the mean first douching age was 14.0 (SD 1.3;
      range 11-16). Douching product users were significantly more likely to know
      someone who douches regularly (P <.0001) and have watched douche commercials (P
      =.0001) than those who did not douche. A majority used store-bought products,
      vinegar in water and scented solution being the most popular; baking soda,
      Betadine, Pine-sol, and Lysol were other products used. Commonly cited reasons
      for douching included to feel good and fresh (60%), and to rid of odor and of
      blood (47% each). Other reasons cited were to please partner (12%) and to avoid
      going to a doctor (6%). Timing of douching included: after period (69%), after
      sex (52%), before sex (16%), before going to a doctor (17%). Among those who
      douched, 51% douched once a month, and an additional 32% more often than that.
      CONCLUSION: This study provides troublesome findings regarding the feminine
      hygiene practices of mostly rural southern teenagers who have been incarcerated.

PMID- 12057532
TI  - Self-mutilation as a manifestation of sexual abuse in adolescent girls.

PMID- 12057534
TI  - Clinical pathologic correlation: Recurrent abdominal pain and primary amenorrhea.

PMID- 12057533
TI  - A comparison of MRI and laparoscopy in detecting pelvic structures in cases of
      vaginal agenesis.
AB  - OBJECTIVE: To determine whether laparoscopy improves detection of uterine
      structures over MRI in cases of vaginal agenesis. DESIGN: Prospective case
      series. SETTING: Ambulatory pediatric gynecology clinic in a tertiary care
      children's hospital. PARTICIPANTS: Subjects with vaginal agenesis who had an MRI
      to detect uterine structures. MAIN OUTCOME MEASURES: A chart review identified
      subjects with vaginal agenesis who had an MRI to assess mullerian structures. The
      MRI findings were correlated with physical exam, presenting symptoms, and
      operative findings. We assessed degree of agreement between laparoscopy and MRI
      in patients both with and without pelvic pain to determine sensitivity and
      specificity of MRI in predicting uterine structures confirmed on laparoscopy.
      RESULTS: Twenty-two subjects with vaginal agenesis were identified and 14 had
      both an MRI and laparoscopic evaluation. MRI successfully predicted uterine
      anomalies in six cases (43%) and lack of uterine structures in one case (8%). MRI
      diagnosis did not correlate with laparoscopic findings in the remaining seven
      cases (50%). Among subjects presenting with no complaints of pelvic pain (n = 6),
      three had negative MR imaging but positive laparoscopy. Using laparoscopy as a
      gold standard, MRI had a sensitivity of 53% for accurately detecting uterine
      anomalies confirmed on laparoscopy. CONCLUSION: Laparoscopy improves detection of
      uterine structures over MRI alone in women with vaginal agenesis.

PMID- 12057535
TI  - In support of metformin use in adolescent polycystic ovary syndrome.

PMID- 12057537
TI  - Chronic pelvic pain in teens.

PMID- 12057536
TI  - Management quandary. Pelvic pain in an adolescent.

PMID- 12057544
TI  - Where health care is not a right.

PMID- 12057545
TI  - Magnesium for preventing and treating eclampsia: time for international action.

PMID- 12057546
TI  - Translocations at 11q23 in childhood ALL: age under 1 and poor prognosis.

PMID- 12057547
TI  - Use of recombinant thyrotropin.

PMID- 12057548
TI  - Nurse-prescribing in the UK: right but also wrong.

PMID- 12057549
TI  - Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?
      The Magpie Trial: a randomised placebo-controlled trial.
AB  - BACKGROUND: Anticonvulsants are used for pre-eclampsia in the belief they prevent
      eclamptic convulsions, and so improve outcome. Evidence supported magnesium
      sulphate as the drug to evaluate. METHODS: Eligible women (n=10141) had not given
      birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more,
      and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty
      about magnesium sulphate. Women were randomised in 33 countries to either
      magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia
      and, for women randomised before delivery, death of the baby. Follow up was until
      discharge from hospital after delivery. Analyses were by intention to treat.
      FINDINGS: Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of
      whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium
      sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women
      allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71)
      than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with
      eclampsia per 1000 women). Maternal mortality was also lower among women
      allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women
      randomised before delivery, there was no clear difference in the risk of the baby
      dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only
      notable difference in maternal or neonatal morbidity was for placental abruption
      (relative risk 0.67, 99% CI 0.45-0.89). INTERPRETATION: Magnesium sulphate halves
      the risk of eclampsia, and probably reduces the risk of maternal death. There do
      not appear to be substantive harmful effects to mother or baby in the short term.

PMID- 12057550
TI  - Death in children with epilepsy: a population-based study.
AB  - BACKGROUND: Families of children with newly diagnosed epilepsy worry about death
      during a seizure. We aimed to assess the frequency and causes of death of
      children with epilepsy. METHOD: We did a population-based cohort study. The Nova
      Scotia epilepsy cohort includes all children who developed epilepsy during 1977
      85. In 1999, we matched names and birth dates with provincial health-care, death,
      and marriage registries. We examined death certificates, necropsy reports, and
      physician records of children who had died and contacted families if sudden
      unexpected death in epilepsy could have occurred. We measured the effect of sex,
      age, epilepsy type, and disorder sufficient to cause functional neurological
      deficit on death rate. We compared cohort mortality with rates in a reference
      population matched for age and sex. FINDINGS: 26 (3.8%) of 692 children with
      epilepsy died. Frequency of death was 5.3 times higher (95% CI 2.29-8.32) than in
      the reference population in the 1980s and 8.8 times higher (4.16-13.43) in the
      1990s. Kaplan-Meier curves showed 6.1% mortality 20 years after onset compared
      with 0.88% in the reference population. Deaths occurred in one (1%) of 97
      children with absence epilepsy, 12 (2%) of 510 with partial and primary
      generalised epilepsy, and 13 (15%) of 85 with secondary generalised epilepsy. 22
      deaths were caused by disorders sufficient to cause functional neurological
      deficit, one by probable sudden unexpected death in epilepsy, two by suicide, and
      one by homicide. Functional neurological deficit was the only independent
      determinant of mortality. INTERPRETATION: Death from epilepsy is uncommon in
      children without a severe neurological disorder sufficient to cause functional
      neurological deficit and sudden unexpected death in epilepsy is rare.

PMID- 12057551
TI  - Constrictive pericarditis and hepatic encephalopathy.

PMID- 12057552
TI  - Sexual mixing patterns and sex-differentials in teenage exposure to HIV infection
      in rural Zimbabwe.
AB  - BACKGROUND: HIV-1 prevalence typically rises more rapidly at young ages in women
      than in men in sub-Saharan Africa. Greater susceptibility to infection on
      exposure in women is believed to be a contributory factor as is greater exposure
      to previously infected sexual partners of the opposite sex. We investigated the
      latter hypothesis using data from a field study in rural Manicaland, Zimbabwe.
      METHODS: Quantitative data on onset and degree of sexual activity, numbers of
      partners, concurrent partnerships, condom use, and partner characteristics were
      used in conjunction with epidemiological data on age and sex specific prevalence
      of HIV infection to do statistical analyses of association between key variables.
      Mathematical models and qualitative data were used to aid analysis and
      interpretation. FINDINGS: Older age of sexual partner was associated with
      increased risk of HIV-1 infection in men (odds ratio 1.13 [95% CI 1.02-1.25]) and
      women (1.04 [1.01-1.07]). Young women form partnerships with men 5-10 years older
      than themselves, whereas young men have relationships with women of a similar age
      or slightly younger. Greater number of lifetime partners is also associated with
      increased risk of HIV (1.03 [1.00-1.05]). Young men report more partners than do
      women but infrequent coital acts and greater use of condoms. These behaviour
      patterns are underpinned by cultural factors including the expectation that women
      should marry earlier than men. A strong gender effect remains after factors that
      affect exposure to infected partners are controlled for (6.04 [1.49-24.47]).
      INTERPRETATION: The substantial age difference between female and male sexual
      partners in Manicaland is the major behavioural determinant of the more rapid
      rise in HIV prevalence in young women than in men. Theoretical studies have
      suggested that this difference is an important determinant of observed
      epidemiological patterns but the study reported in this paper provides clear
      empirical evidence of association.

PMID- 12057553
TI  - Specific airway resistance in 3-year-old children: a prospective cohort study.
AB  - BACKGROUND: The development of a method to assess lung function in young children
      may provide new insight into asthma development. Plethysmographic measurement of
      specific airway resistance (sR(aw)) is feasible in this age group. We aimed to
      identify risk factors associated with low lung function in early childhood in a
      prospective birth cohort. METHODS: Children were prenatally assigned to risk
      group according to parental atopic status (high risk, both parents atopic; medium
      risk, one parent atopic; low risk, neither parent atopic) and followed
      prospectively until age 3 years. We measured sR(aw) in 503 symptom-free children
      using whole-body plethysmography during tidal breathing. FINDINGS: 803 of 868
      children attended the clinic, of whom 503 obtained satisfactory sR(aw) readings.
      200 who wheezed at least once during first 3 years of life had significantly
      higher sR(aw) than the 303 who had never wheezed (mean difference 5.8%, 95% CI
      2.2-9.3, p=0.002). For children who had never wheezed there were significant
      differences in sR(aw) between risk groups (p<0.001). Children at high risk (n=87)
      had a higher sR(aw) (geometric mean 1.17 kPa/s, 1.12-1.22) than children at
      medium risk (n=162; 1.02 kPa/s, 1.00-1.05) and at low risk (54; 1.04 kPa/s, 0.99
      1.11). Atopic children (n=62) had significantly higher sR(aw) (1.15 kPa/s, 1.09
      1.21) than those who were not atopic (232; 1.05 kPa/s, 1.02-1.07, p=0.002). For
      non-atopic children, those at high risk (58) had higher sR(aw) (1.13kPa/s, 1.07
      1.18) than those at medium risk (125, 1.01kPa/s, 0.98-1.05) or at low risk (49,
      1.04 kPa/s, 0.97-1.10, p=0.003). We showed a significant interaction between
      history of maternal asthma and child's atopic status (p=0.006). INTERPRETATION:
      Even in the absence of respiratory symptoms, children of atopic parents and those
      with personal atopy have impaired lung function in early life.

PMID- 12057555
TI  - Just another corneal abrasion?

PMID- 12057554
TI  - Outcome of treatment in childhood acute lymphoblastic leukaemia with
      rearrangements of the 11q23 chromosomal region.
AB  - BACKGROUND: The prognosis and optimum treatment of childhood acute lymphoblastic
      leukaemia (ALL) with abnormalities of chromosomal band 11q23 are controversial.
      We aimed to identify prognostic factors that might help in planning future
      therapy, and to assess the effectiveness of haemopoietic stem-cell
      transplantation in patients with the t(4;11) translocation, which is associated
      with a particularly poor outcome. METHODS: We reviewed data on 497 children and
      young adults who had ALL with various 11q23 abnormalities, including the
      translocations t(4;11), t(9;11), and t(11;19). All patients were treated with
      intensive chemotherapy, with or without haemopoietic stem-cell transplantation in
      first complete remission, by 11 study groups and single institutions from 1983 to
      1995. FINDINGS: Age was the most important prognostic factor. In a Cox's
      proportional-hazard model stratified by 11q23 abnormalities, infants younger than
      1 year fared significantly worse than patients 1 year of age or older (hazard
      ratio for event-free survival 1 84 [95% CI 1 38-2 47], p=0 0001). Among infants,
      any category of 11q23 abnormality conferred a dismal outcome, whereas in older
      patients, t(4;11) and t(9;11) were associated with a worse outcome than were
      other 11q23 changes. In the largest subgroup--256 patients with t(4;11)--any type
      of transplantation was associated with significantly worse disease-free survival
      (1 61 [1 10-2 35], p=0 014) and overall survival (1 76 [1 08-2 45], p=0 004)
      compared with chemotherapy only. Even transplantation with stem cells from HLA
      matched related or HLA-matched unrelated donors tended to be associated with a
      worse outcome than chemotherapy alone. INTERPRETATION: The prognosis of acute
      lymphoblastic leukaemia with an 11q23 abnormality is particularly dismal in
      infants. Allogeneic transplantation with haemopoietic stem cells from an HLA
      matched related donor does not seem to improve the clinical outcome in patients
      with t(4;11)-positive leukaemia.

PMID- 12057556
TI  - Analysis of minichromosome maintenance proteins as a novel method for detection
      of colorectal cancer in stool.
AB  - Colorectal cancer is a common disease, and more reliable screening methods are
      needed for early detection. We aim to develop a non-invasive, stool-based assay
      that can identify colorectal cancer by detection of minichromosome maintenance
      protein 2 (MCM2) expression in colonocytes retrieved from the faecal surface. We
      devised a cell line model to investigate methods and conditions for optimum
      colonocyte retrieval. In our clinical evaluation study, MCM2-positive cells were
      retrieved from 37 of 40 patients with symptomatic colorectal cancer, but from
      none of 25 healthy control individuals. These results suggest that
      immunocytochemical analysis of retrieved colonocytes might enable accurate
      detection of colorectal cancer in stool.

PMID- 12057557
TI  - Cost-effectiveness of screening for the factor V Leiden mutation in pregnant
      women.
AB  - The factor V Leiden (FVL) mutation is associated with vascular complications in
      pregnancy, and routine screening of all pregnant women has been suggested. We did
      a prospective, unselected study in 967 pregnant women to evaluate the cost
      effectiveness of screening all women, or only those with a personal or family
      history of venous thrombosis (n=113). When anticoagulant prophylaxis was assumed
      to effect a 50% reduction in vascular complications, we recorded an additional
      management cost of 3768 pounds sterling with selective screening and 39,841
      pounds sterling with universal screening. This additional cost would result in
      prevention of less than one and three vascular events,respectively. Our findings,
      therefore, suggest that screening of pregnant women for the FVL mutation is not
      cost-effective.

PMID- 12057558
TI  - Reliability of diagnosis of melanoma in situ.
AB  - Early and correct diagnosis of malignant melanoma is of utmost importance to
      ensure adequate treatment and the best outcome. Prompted by the death of a
      patient with an apparent metastasising melanoma in situ, we reassessed 104 people
      with this malignant disorder, whose diagnosis had been histopathologically
      verified. We did immunohistochemical analysis of cells with the melanocytic
      marker melan-A/MART-1, and results of this analysis showed that 30 (29%) of 104
      patients had invasive melanomas. One patient died of distant metastases, and the
      tumour recurred in another. Our finding could be relevant for diagnosis and
      treatment of melanoma in situ.

PMID- 12057559
TI  - The dangers of conformity.

PMID- 12057560
TI  - US drug industry and FDA prepare for closer ties.

PMID- 12057561
TI  - Does mucus hypersecretion matter in airway disease?

PMID- 12057562
TI  - German ethics group advises against pre-implantation genetic diagnosis.

PMID- 12057564
TI  - Start tamoxifen after completing chemotherapy, US researchers say.

PMID- 12057565
TI  - Spain's drug industry agrees to ethical drug promotion behaviour.

PMID- 12057566
TI  - Increased use of amphetamine-type stimulants threatens east Asian countries.

PMID- 12057567
TI  - Kenyan board to draw up guidelines to end inappropriate use of painkillers.

PMID- 12057568
TI  - Government gives hospitals greater independence.

PMID- 12057569
TI  - Diagnosis of osteoporosis and assessment of fracture risk.
AB  - The diagnosis of osteoporosis centres on the assessment of bone mineral density
      (BMD). Osteoporosis is defined as a BMD 2.5 SD or more below the average value
      for premenopausal women (T score < -2.5 SD). Severe osteoporosis denotes
      osteoporosis in the presence of one or more fragility fractures. The same
      absolute value for BMD used in women can be used in men. The recommended site for
      diagnosis is the proximal femur with dual energy X-ray absorptiometry (DXA).
      Other sites and validated techniques, however, can be used for fracture
      prediction. Although hip fracture prediction with BMD alone is at least as good
      as blood pressure readings to predict stroke, the predictive value of BMD can be
      enhanced by use of other factors, such as biochemical indices of bone resorption
      and clinical risk factors. Clinical risk factors that contribute to fracture risk
      independently of BMD include age, previous fragility fracture, premature
      menopause, a family history of hip fracture, and the use of oral corticosteroids.
      In the absence of validated population screening strategies, a case finding
      strategy is recommended based on the finding of risk factors. Treatment should be
      considered in individuals subsequently shown to have a high fracture risk.
      Because of the many techniques available for fracture risk assessment, the 10
      year probability of fracture is the desirable measurement to determine
      intervention thresholds. Many treatments can be provided cost-effectively to men
      and women if hip fracture probability over 10 years ranges from 2% to 10%
      dependent on age.

PMID- 12057570
TI  - The art of making ineffective treatments effective.

PMID- 12057571
TI  - Paradoxical physical findings described by Kussmaul: pulsus paradoxus and
      Kussmaul's sign.

PMID- 12057572
TI  - Helicobacter pylori and peptic-ulcer disease.

PMID- 12057573
TI  - Helicobacter pylori and peptic-ulcer disease.

PMID- 12057576
TI  - Quantitative detection of serum adenovirus in a transplant recipient.

PMID- 12057577
TI  - Absolute and relative truth in clinical trials.

PMID- 12057579
TI  - Thyroid cancer 15 years after Chernobyl.

PMID- 12057581
TI  - Thyroid cancer 15 years after Chernobyl.

PMID- 12057583
TI  - Hepatitis A vaccine failure.

PMID- 12057582
TI  - Mass drug administration to treat lymphatic filariasis.

PMID- 12057584
TI  - Medical triage and legal protection in Japan.

PMID- 12057585
TI  - Experience of leprosy.

PMID- 12057586
TI  - Industry funding in medical education.

PMID- 12057587
TI  - Pharmaceutical industry profits and cost to senior citizens' health.

PMID- 12057588
TI  - Blister beetles and the ten plagues.

PMID- 12057593
TI  - Splenitis.

PMID- 12057596
TI  - Reduction of animal use in human vaccine quality control: opportunities and
      problems.
AB  - In vivo assays play a crucial role in the assessment of the potency and safety of
      human vaccines. Robust vaccine production procedures, improved characterisation
      methods and development of well-characterised vaccines create possibilities to
      reduce animal use. In this paper the current status in this field is reviewed.
      Achievements with regard to in vivo and in vitro potency and safety testing are
      discussed as well as new developments and possibilities in the field of in vitro
      characterisation of vaccine components. Finally, validation and implementation
      issues will be dealt with. Although replacement of in vivo tests for batch
      release of existing vaccines is difficult, emerging technologies allow well
      considered reduction of in vivo experiments during product and process
      development and improvement. Inextricably bound up with this approach is good
      manufacturing practice (GMP), resulting in robust, validated production
      processes.

PMID- 12057597
TI  - A dilemma for mucosal vaccination: efficacy versus toxicity using enterotoxin
      based adjuvants.
AB  - In the development of mucosal vaccines, cholera toxin (CT) has been shown to be
      an effective adjuvant and to induce both mucosal and systemic immune responses
      via a Th2 cell-dependent pathway. However, a major concern for use of mucosal
      adjuvants such as CT is that this molecule is not suitable for use in humans
      because of its innate toxicity. Recent vaccine development efforts have
      emphasized nasal application of antigen and CT for the induction of mucosal IgA
      responses. When we examined potential toxicity of CT for the central nervous
      system (CNS), both CT and CT-B accumulated in the olfactory nerves/epithelium and
      olfactory bulbs of mice when given by the nasal route. The development of
      effective mucosal vaccines for the elderly is also an important issue; however,
      only limited information is available. When mucosal adjuvanticity of CT was
      evaluated in aged mice, an early immune dysregulation was evident in the mucosal
      immune system. The present review discusses these potential problems for
      effective mucosal vaccine development.

PMID- 12057598
TI  - Recombinant cysteine proteinases-based vaccines against Leishmania major in
      BALB/c mice: the partial protection relies on interferon gamma producing CD8(+) T
      lymphocyte activation.
AB  - Together with poloxamer 407 as adjuvant the recombinant type I (rCPB) or type II
      (rCPA) cysteine proteinases of Leishmania major were screened as potential
      vaccines against L. major in a mouse model. The vaccines were delivered
      subcutaneously twice at 3 weeks intervals. Three weeks after booster injection,
      5x10(5) stationary phase L. major promastigotes were inoculated subcutaneously in
      one footpad. Using the footpad thickness increase to monitor the clinical
      outcome/cutaneous lesion at site of L. major delivery, it was possible to
      document that rCPB but not rCPA allowed BALB/c mice to mount a partial protective
      response: indeed over the period under study (weeks 1-12) a clear delay was
      noticed after the immunization with rCPB. This partial protective effect was no
      more detectable if CD8 depleting antibody was given intravenously to rCPB
      immunized mice, at the time of parasite challenge. Seven weeks after challenge,
      the draining lymph nodes were monitored for their frequencies of IFN-gamma
      positive CD4(+) and CD8(+) T lymphocytes using PMA and ionomycin as re-activating
      signals: interestingly the partial protection achieved in BALB/c mice immunized
      with rCPB together with poloxamer was correlated only to one immunological
      parameter, namely the higher frequency of IFN-gamma producing CD8(+) T
      lymphocytes. Of note also, in the lymph node draining the L. major-loaded footpad
      of C57BL/6 mice otherwise known to develop a transient lesion, the frequency of
      IFN-gamma producing CD8(+) T lymphocytes reach similar value 7 weeks after
      challenge and in absence of any prior immunization. Taken together, it was shown
      that the induced partial protection was mainly dependent on IFN-gamma producing
      CD8(+) T cells.

PMID- 12057599
TI  - Antibody responses induced by immunization with a Japanese rabies vaccine
      determined by neutralization test and enzyme-linked immunosorbent assay.
AB  - The immunogenicity of a Japanese purified chick embryo cell culture rabies
      vaccine (PCECV) was examined. Serum samples were obtained from 86 subjects after
      pre-exposure or post-exposure prophylaxis. Rabies antibody titres were determined
      by neutralization test and enzyme-linked immunosorbent assay (ELISA). Titres
      higher than 0.5 international units (IU)/ml were demonstrated by neutralization
      test in all the 19 subjects after three-time pre-exposure immunization on days 0,
      30 and 180. Titres higher than 0.5IU/ml were also demonstrated by neutralization
      test in all the 23 subjects after four-time post-exposure immunization on days 0,
      3, 7 and 14. There was a correlation between neutralization and ELISA antibody
      titres (r=0.697); however, neutralization titers were higher than ELISA titres
      for most of the samples. The results suggest that current Japanese rabies vaccine
      induces recommended levels of neutralizing antibodies after pre- and post
      exposure prophylaxes.

PMID- 12057600
TI  - Vaccination of cats with an attenuated recombinant myxoma virus expressing feline
      calicivirus capsid protein.
AB  - Myxoma virus, a member of the Poxviridae family (genus Leporipoxvirus) is the
      agent responsible for myxomatosis in the European rabbit. Recombinant myxoma
      viruses expressing the capsid gene of an F9 strain of feline calicivirus (FCV)
      were constructed from an apathogenic, laboratory attenuated, isolate of myxoma
      virus. The FCV capsid genes were recombined into the myxoma growth factor (MGF)
      locus of the myxoma genome and expressed from synthetic poxvirus promoters.
      Myxoma virus is unable to replicate productively in feline cells in vitro,
      however, cells infected with recombinant viruses do express the heterologous
      antigens from both late and early/late synthetic promoters. Cats immunised with
      myxoma-FCV recombinant virus generated high levels of serum neutralising antibody
      and were protected from disease on subsequent challenge with virulent FCV.
      Furthermore, there was no evidence of transmission of myxoma-FCV recombinant
      virus from vaccinated to non-vaccinated cats. These results demonstrate the
      potential of myxoma virus as a safe vaccine vector for use in non-lepori species
      and in particular the cat.

PMID- 12057601
TI  - Induction of HLA-A2-restricted CTL responses by a tubular structure carrying
      human melanoma epitopes.
AB  - Epitope-based vaccination strategies designed to induce strong tumor-specific
      CD8(+) T cell responses are being widely considered for cancer immunotherapy.
      Here, two recombinant tubular structures, NS1-Mela 1 and NS1-Mela 2, carrying,
      respectively two HLA-A2 epitopes derived from human melanoma antigens were
      constructed and their capability to induce CTL responses in vivo were studied in
      HLA-A2 transgenic mice. Strong CTL responses specific for GnT-V/NA 17-A and gp100
      (154-162) epitopes were generated in HLA-A2 transgenic mice immunized by the
      construct NS1-Mela l carrying these two epitopes. The second construct NS1-Mela 2
      carrying both Tyrosinase (369-377Da) and Melan-A/Mart-1 (27-35) epitopes induced
      a weak Tyrosinase-specific CTL response in mice but failed to induce specific CTL
      responses against the Melan-A/Mart-1 (27-35) epitope in the tested mice. Thus,
      recombinant tubular structures containing multiple tumoral epitopes may lead to
      new strategies for the induction of strong tumor-specific CTL responses in cancer
      patients.

PMID- 12057602
TI  - Development of a high-performance anion-exchange chromatography with pulsed
      amperometric detection based quantification assay for pneumococcal
      polysaccharides and conjugates.
AB  - A method, using high-performance anion-exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD), has been developed to determine the
      concentrations of Streptococcus pneumoniae capsular polysaccharides and
      polysaccharide conjugates used in formulating a conjugate vaccine for the
      prevention of pneumococcal infections. In an effort to determine optimum
      hydrolysis conditions for the analysis, pneumococcal polysaccharides were
      subjected to three different hydrolysis methods: trifluoroacetic acid (TFA)
      hydrolysis, methanolysis followed by TFA hydrolysis, or hydrofluoric acid (HF)
      hydrolysis followed by TFA hydrolysis. For quantification purposes, best results
      were obtained by methanolysis followed by TFA hydrolysis for uronic acid
      containing polysaccharides, and by TFA hydrolysis for all the others. For the
      quantification of all the polysaccharides (from native to conjugated forms), a
      monosaccharide reference mixture (Rha, Gal and GlcA) hydrolyzed along with the
      samples can be used as standards for routine analysis. This is much more
      convenient than to hydrolyze a well-characterized reference polysaccharide
      (necessary standard only for type 1 capsular polysaccharide). This method is
      rapid, very sensitive (less than 10 microg of polysaccharide is required), and
      may replace advantageously the currently used colorimetric assays used to
      determine polysaccharides content. Moreover, it can be readily adapted for use
      with other bacterial polysaccharide preparations as well.

PMID- 12057603
TI  - Characterization of a Vero cell-adapted virulent strain of enterovirus 71
      suitable for use as a vaccine candidate.
AB  - Enterovirus 71 (EV71) is a neurotrophic virus that causes seasonal morbidity and
      mortality in children throughout the world with increasing frequency in recent
      years. Because of the lack of an effective antiviral agent, primary prevention,
      including the development of effective vaccines, is a top priority in terms of
      control strategies. Poliovirus vaccine technology, both live attenuated and
      inactivated, killed virus vaccines, can be adopted for use with EV71 because of
      their relatedness. In this study, we have characterized a laboratory-adapted EV71
      strain, YN3-4a, which exhibits different characteristics from those of its parent
      isolate, neu, in having a rapid growth rate in Vero cells, a larger plaque size,
      and a lower LD(50) in newborn mice. The YN3-4a can be produced at a high viral
      titer of up to 10(10) tissue culture infective dose (TCID(50)) when grown in Vero
      cells, an approved substrate for virus vaccine production. Mouse antiserum raised
      against YN3-4a can neutralize a broad range of strains of EV71 isolated at
      different times from a variety of geographic regions. On passage in Vero cells,
      YN3-4a remained genetically and phenotypically stable. Many of the above
      described features, such as high viral yield, strong immunogenicity, broad-based
      antigenic coverage, and passage stability, are desirable features in a prototype
      virus for the development of an inactivated viral vaccine.

PMID- 12057604
TI  - Efficacy and cost-effectiveness of influenza vaccination of the elderly in a
      densely populated and unvaccinated community.
AB  - For economic reasons, the few influenza vaccination programs seen in developing
      countries are aimed at the high-risk elderly. To evaluate its efficacy and cost
      effectiveness, we conducted a 2-month influenza vaccination campaign in southern
      Taiwan's A-Lein township for all the elderly. Significant differences in
      hospitalization and mortality between the vaccinated and unvaccinated groups were
      found. Age, sex, and risk group were significant for hospitalization and
      mortality, but only vaccination was significant for prevention. Savings for each
      person vaccinated were at least three times the cost of vaccination. We strongly
      recommend that all the elderly-not only high-risk elderly--receive an annual
      influenza vaccination.

PMID- 12057605
TI  - Exposure to varicella boosts immunity to herpes-zoster: implications for mass
      vaccination against chickenpox.
AB  - We present data to confirm that exposure to varicella boosts immunity to herpes
      zoster. We show that exposure to varicella is greater in adults living with
      children and that this exposure is highly protective against zoster (Incidence
      ratio=0.75, 95% CI, 0.63-0.89). The data is used to parameterise a mathematical
      model of varicella zoster virus (VZV) transmission that captures differences in
      exposure to varicella in adults living with and without children. Under the 'best
      fit' model, exposure to varicella is estimated to boost cell-mediated immunity
      for an average of 20 years (95% CI, 7-41years). Mass varicella vaccination is
      expected to cause a major epidemic of herpes-zoster, affecting more than 50% of
      those aged 10-44 years at the introduction of vaccination.

PMID- 12057606
TI  - Experimental studies with foot-and-mouth disease virus, strain O, responsible for
      the 2001 epidemic in the United Kingdom.
AB  - In 2001, the United Kingdom experienced its worst epidemic of foot-and-mouth
      disease (FMD). To date approximately 3.9 million animals have been culled and
      direct and indirect revenue losses are probably in excess of pound 12 billion.
      This study was carried out to investigate the biological characteristics of the
      FMD virus strain O/UKG/2001 responsible for the epidemic. Animal transmission
      experiments indicated that this strain is not host restricted and will infect the
      three main susceptible livestock species (cattle, sheep and pigs). Immunisation
      with high potency emergency vaccine derived from O(1) Manisa strain of FMD virus
      protected all three species against clinical disease when challenged with FMD
      virus strain O/UKG/2001.

PMID- 12057607
TI  - Influenza and pneumococcal vaccination in Scottish nursing homes: coverage,
      policies and reasons for receipt and non-receipt of vaccine.
AB  - A national survey was carried out to determine the coverage of influenza and
      pneumococcal vaccines, policies, reasons for receipt, non-receipt of vaccine and
      strategies to improve vaccine coverage in Scottish nursing homes. Of the 550
      nursing homes, 72% (394) participated in the study. Overall coverage was 85% for
      influenza vaccine in 2001-2002 season and 11% for pneumococcal vaccine in the
      last 5-year period. Only 6% (23/394) of homes were reported to have a systematic
      immunization record. The most frequently stated reasons for improved coverage of
      both vaccines were clear immunization policies (76%), awareness and education for
      staff and residents (68%), and consent on behalf of the incompetent residents
      (66%). The presence of vaccination policies was higher for influenza vaccine than
      pneumococcal vaccine expressed as verbal agreement (27% versus 3%), written
      policies with set target (24% versus 5%) and written policies without set target
      (17% versus 2%). Advice from the members of the community health care team was
      the principal reason for the receipt of both vaccines. The predominant reasons
      for non-receipt of vaccine were refusal by residents and family members (both
      vaccines) and lack of advice from general practitioners (pneumococcal vaccine).
      The substantial disparity in coverage of influenza and pneumococcal vaccine
      reflects the lack of national recommendations and policies for reimbursements for
      pneumococcal vaccination. These data suggest that greater efforts are needed to
      improve prevention behaviors of health care professionals and the public,
      organized vaccine delivery strategies and systematic vaccination documents to
      increase influenza and pneumococcal vaccination rates in nursing homes and other
      long-term care facilities.

PMID- 12057608
TI  - Efficacy of a B virus gD DNA vaccine for induction of humoral and cellular immune
      responses in Japanese macaques.
AB  - It is desirable to prevent dissemination of B virus (BV) in macaque colonies
      because transmission of BV to humans causes deadly encephalomyelitis. Vaccination
      of monkeys is one method that could confine spread of BV within macaque colonies.
      Availability of a BV DNA vaccine for use in macaques would eliminate the risk of
      working with infectious BV. Toward this end, we constructed a plasmid expressing
      the BV glycoprotein D (gD). Immunogenicity of this construct as a DNA vaccine was
      assessed in adult Japanese macaques by four intracutaneous injections at a dose
      of 500 microg per head. Results of enzyme-linked immunosorbent assay (ELISA)
      using a recombinant herpes simplex virus type 1 (HSV1) gD, a homologue of BV gD,
      showed that significant levels of antibody was induced in all vaccinated animals
      following each booster injection. Western blot of sera from vaccinated macaques
      confirmed the specific recognition of authentic BV gD. Immune sera were also
      demonstrated to contain neutralizing activity against infectious BV. Weak
      lymphoproliferative responses were also observed in vaccinated macaques using
      recombinant HSV1 gD as a stimulating antigen and flow cytometry analysis of one
      individual revealed the presence of HSV1 gD-responsive effector T cells. Thus,
      the BV gD DNA vaccine was demonstrated to induce both humoral and cellular immune
      responses in macaques which recognized BV gD.

PMID- 12057609
TI  - The effectiveness of serogroup C meningococcal vaccine estimated from routine
      surveillance data.
AB  - Serogroup C meningococcal vaccine effectiveness was estimated from routine
      surveillance data, based on a comparison of the proportion of vaccine and non
      vaccine serogroups in vaccinated and unvaccinated reported cases. Between 1 April
      1993 and 31 March 1998, 109 eligible cases were reported. Among the 54 cases
      caused by serogroup C, 38 had been vaccinated. Among the 55 cases caused by non
      vaccine serogroups, 49 had been vaccinated. Vaccine effectiveness was estimated
      at 71% (95% CI: 21-89%), a value similar to that obtained in the same population
      by a cohort study. Effectiveness was lower in children immunized before the age
      of 10. This demonstrates that meningococcal vaccine effectiveness can be
      estimated from information obtained routinely from cases only, as an alternative
      to the more expensive cohort or case-control designs.

PMID- 12057610
TI  - Intranasal immunization with SIV virus-like particles (VLPs) elicits systemic and
      mucosal immunity.
AB  - By using a baculovirus expression system, we have successfully produced simian
      immunodeficiency virus (SIV)-like particles (VLPs) with high levels of
      biologically active SIV envelope (Env) incorporated on their surfaces. To study
      whether SIV VLPs represent effective mucosal immunogens, we immunized groups of
      mice with VLPs alone or VLPs plus the mucosal adjuvant cholera toxin (CT) by the
      intranasal (i.n.) route. High levels of serum IgG antibody production were
      achieved in mice immunized intranasally with SIV VLPs, and the antibody response
      was found to be antigen dose-dependent. The IgG1 and IgG2a ratio indicates that
      immune responses induced by SIV VLPs are Th1 oriented. Mice immunized with VLPs
      plus CT were found to exhibit higher serum antibody responses than those
      immunized with VLPs alone (P<0.001). Furthermore, IgA antibody production was
      detected in both saliva and vaginal fluid from mice mucosally immunized with SIV
      VLPs. Higher levels of IgA were found in vaginal fluid than in saliva in animals
      immunized with SIV VLPs plus CT (P<0.05). Higher neutralizing activity to SIV
      1A11 was also found in serum of animals immunized with SIV VLPs plus CT.
      Moreover, increased numbers of MHC I-restricted peptide-specific IFN-gamma and IL
      4 producing T cells were detected in both splenocytes and lymph nodes by
      intranasal immunization of SIV VLP plus CT. These results suggest that VLPs are
      effective mucosal antigens that can induce both humoral and cellular immune
      responses at systemic and mucosal sites.

PMID- 12057611
TI  - Identification of Brucella melitensis vaccine strain Rev.1 by PCR-RFLP based on a
      mutation in the rpsL gene.
AB  - The live attenuated strain B. melitensis Rev.1 is considered the best vaccine
      available for the prophylaxis of brucellosis in sheep and goats. The Rev.1
      vaccine was obtained in the 1950s by a two-step selection involving firstly
      streptomycin resistance and dependence and secondly reversion of dependence but
      keeping streptomycin resistance. Chromosomally acquired streptomycin resistance
      is frequently due to mutations in the gene encoding the ribosomal protein S12,
      rpsL. Nucleotide sequencing revealed one mutation in the rpsL gene of vaccine
      strain Rev.1 compared to that of reference strain 16M leading to an amino acid
      Pro-to-Leu change at codon position 91 (Pro91Leu). This mutation resulted also in
      the lack of a NciI restriction site in the gene. PCR-restriction fragment length
      polymorphism (PCR-RFLP) using NciI applied to a large number of Brucella
      reference and field strains showed that the mutation detected was specific of
      vaccine strain Rev.1.

PMID- 12057612
TI  - Effects of adsorption of acellular pertussis antigens onto different aluminium
      salts on the protective activity in an intranasal murine model of Bordetella
      pertussis infection.
AB  - Adsorption of the pertussis antigens, pertussis toxoid (PT), filamentous
      hemagglutinin (FHA) and pertactin (PRN) onto aluminium phosphate rather than
      aluminium hydroxide leads to a lower humoral response and poorer protection
      against intranasal pertussis challenge in mice. These effects could be reversed
      by inclusion of fimbriae (FIM) 2 and 3 in the formulation. These data emphasis
      the importance of correct formulation for such vaccines.

PMID- 12057613
TI  - Production and immunogenic efficacy of botulinum tetravalent (A, B, E, F) toxoid.
AB  - A tetravalent (type A, B, E and F) toxoid was produced and its efficacy and
      safety were assessed. The toxoid preparation was inoculated from two to five
      times to 15 healthy adult volunteers participating in botulinum toxin research.
      The serum samples taken from the toxoid recipients were titrated for the
      antitoxin potencies by enzyme-linked immunosorbent assay (ELISA) and the
      neutralization test. The neutralizing and ELISA titers were too low to correlate
      each other. The mean neutralization titer of four recipients in 9 months after
      three doses of toxoid was about 0.1IU/ml for each of the four types, whereas, the
      one receiving five doses possessed a higher titer. Since the amount of the toxin
      handled in laboratory work is usually not so large, three or more doses of the
      present toxoid will bestow sufficient immunity on the workers participating in
      botulinum research. Nevertheless booster injections might be desirable to those
      at higher risk, handling the toxin of a high concentration.

PMID- 12057614
TI  - Economic evaluation of strategies for the control and management of influenza in
      Europe.
AB  - We compared the cost-effectiveness of different strategies for the control and
      management of influenza for the elderly populations in three European countries
      (England and Wales, France, Germany). A "no intervention" scenario was compared
      with six control strategies: opportunistic vaccination (passive recruitment),
      comprehensive vaccination programmes (active recruitment), 4 weeks
      chemoprophylaxis course using neuraminidase inhibitors (NIs), 4 weeks
      chemoprophylaxis course using ion-channel inhibitors (ICIs), early treatment with
      NIs, and early treatment with ICIs. Vaccination strategies were the most cost
      effective. Chemoprophylaxis strategies were highly expensive even under
      assumptions of optimal timing. Early treatment strategies with antivirals
      substantially increased demand for GP services and were more expensive than
      prevention through vaccination.

PMID- 12057615
TI  - Long term (24 months) follow-up of a hepatitis A and B vaccine, comparing a two
      and three dose schedule in adolescents aged 12-15 years.
AB  - BACKGROUND: A two dose schedule (0 and 6 months) for a combined hepatitis A and B
      vaccine is currently being developed. METHODS: The present study compared the
      combined hepatitis A and B vaccines in 12-15-year-old: Twinrix paediatric (360
      EL.U HAV antigen/10 microg HBs antigen) on a three dose schedule (0, 1 and 6
      months) to the adult formulation (720 EL.U HAV antigen/20 microg HBs antigen) on
      a two dose schedule (0 and 6 months) and also reports on the follow-up until 24
      months. RESULTS: Seroconversion (SC) rates to HAV in both regimens reached 100%
      by month 7 and remained 100% up to month 24. Anti-HAV, GMTs were slightly higher
      for the two dose than the three dose regimens at this time point. Seroprotection
      against hepatitis B was >99% in both groups by month 7 and 24, this was still 94
      and 96%, respectively. Statistical non-inferiority of group 1 (two dose) versus
      group 2 (three dose) was demonstrated. All vaccines were well tolerated and the
      most frequently reported local and general symptoms were pain and fatigue. There
      were no vaccine-related serious adverse events reported during the study.
      CONCLUSION: The two dose regimen elicited similar immunogenicity to HAV and HBsAg
      and reactogenicity profiles as the three dose regimen in this group of healthy
      adolescents. The reduction in the number of doses from the current three dose
      schedule will make vaccination against hepatitis A and B more convenient to the
      vaccinee, reduce healthcare staff time required and may lower the overall costs
      associated with vaccination.

PMID- 12057616
TI  - Private demand for a HIV/AIDS vaccine: evidence from Guadalajara, Mexico.
AB  - The private demand for a hypothetical vaccine that would provide lifetime
      protection against HIV/AIDS to an uninfected adult was measured in Guadalajara,
      Mexico, using the concept of willingness to pay (WTP). A 91-question survey
      instrument was administered by trained enumerators employing contingent valuation
      techniques to 234 adults, aged 18-60. Our estimates of private demand indicate
      that individuals anticipate sizable personal benefits from such a vaccine, and
      that they would be willing to allocate a substantial portion of their income to
      be protected in this way from HIV infection. A conservative estimate of the mean
      WTP of adults in the Guadalajara sample is 6358 pesos (669 US dollars) and the
      median is 3000 pesos (316 US dollars). A multivariate statistical analysis of the
      determinants of individuals' WTP shows that individuals with higher incomes, with
      spouses or partners, and with higher perceived risks of becoming infected with
      HIV are willing to pay more for the vaccine. Older respondents are willing to pay
      less. These results suggest that there is likely to be a potentially large
      private market for a HIV/AIDS vaccine in the middle-income developing countries
      such as Mexico. These findings have important implications both for the level of
      R&D effort that is devoted to a vaccine and, assuming these efforts are
      successful, for future policies to make the vaccine available to the public.

PMID- 12057617
TI  - Avidity maturation following vaccination with a meningococcal recombinant
      hexavalent PorA OMV vaccine in UK infants.
AB  - To date, there are no data assessing the utility of avidity indices as a
      surrogate marker for the induction of immunological memory following
      meningococcal serogroup B outer membrane vesicle (OMV) vaccination. We studied
      infants who had been immunized with three doses of a recombinant hexavalent PorA
      OMV vaccine at ages 2-4 months, together with a fourth dose at age 12-18 months.
      A control group had received a single dose of the same vaccine at age 12-18
      months. As previously reported, serum bactericidal antibody (SBA) titres
      increased after each of the first three doses, with a significant increase
      observed from 6 months post third dose to 1 month post fourth dose. The geometric
      mean avidity indices (GMAI), against strain H44/76 OMVs, increased from 1 month
      post first dose to 1 month post third dose. Significant increases in GMAI were
      observed at 6 months post third dose and again following the fourth dose. At 32
      42 months of age, though the SBA titres had returned to post first dose levels,
      the GMAI remained elevated. No increase in avidity was observed in the control
      group. Antibody avidity indices are useful laboratory markers for the priming of
      immunological memory following vaccination with meningococcal serogroup B OMV
      vaccines.

PMID- 12057618
TI  - Immune response of HLA DQ2 positive subjects, vaccinated with HBsAg/AS04, a
      hepatitis B vaccine with a novel adjuvant.
AB  - About 5-10% of the general adult population respond inadequately to hepatitis B
      vaccination. The histocompatibility leucocyte antigen (HLA) DQ2, DR3 and DR7
      phenotypes have been linked with non-responsiveness to hepatitis B vaccination. A
      first part of our study determined the prevalence of the HLA DQ2 allele in a
      healthy population, aged 15-50 years. We found 35% of our study population
      (n=1008) positive for the HLA DQ2 allele. Positive subjects for HLA DQ2 were
      subsequently invited to participate in a trial and were to be given either the
      HBsAg/AS04 hepatitis B vaccine or a licensed hepatitis B vaccine (Engerix-B).(1)
      Both contained 20 microg of recombinant HBsAg. The HBsAg/AS04 vaccine was
      administered on a 0 and 6 months schedule whilst the comparator vaccine was given
      according to the standard 0, 1 and 6 months schedule. The experimental vaccine
      was formulated on a novel adjuvant containing 3' deacylated monophosphoryl lipid
      A (3D-MPL) and alum. A total of 230 subjects were enrolled into the vaccination
      study. At month 7, 99% of the subjects had a protective titre (>or=10mIU/ml) with
      a geometric mean titre (GMT) of 6613mIU/ml in the group receiving HBsAg/AS04
      versus 97% seroprotected with a GMT of 2315mIU/ml in the other group. Both
      vaccines, with their respective schedule, give very high seroprotection rates
      (>96%). Our data suggest that HLA DQ2 positivity is not a good marker for non- or
      poor-responsiveness. The HBsAg/AS04 vaccine was more reactogenic mainly because
      of an increased local reactogenicity. Both vaccines, especially HBsAg/AS04, are
      highly immunogenic and well tolerated by the study subjects.

PMID- 12057619
TI  - Effective synthetic peptide vaccine for foot-and-mouth disease in swine.
AB  - We have designed a peptide-based vaccine for foot-and-mouth disease (FMD)
      effective in swine. The peptide immunogen has a G-H loop domain from the VP1
      capsid protein of foot-and-mouth disease virus (FMDV) and a novel promiscuous T
      helper (Th) site for broad immunogenicity in multiple species. The G-H loop VP1
      site was optimised for cross-reactivity to FMDV by the inclusion into the peptide
      of cyclic constraint and adjoining sequences. The incorporation of consensus
      residues into the hypervariable positions of the VP1 site provided for broad
      immunogenicity. The vaccine protected 20 out of 21 immunised pigs from infectious
      challenge by FMDV O1 Taiwan using peptide doses as low as 12.5 microg, and a mild
      adjuvant that caused no lesions. A safe chemically-defined product would have
      considerable advantages for vaccination against FMD.

PMID- 12057620
TI  - Evaluation of adverse effects of vaccines: the case-control approach.
AB  - When the hypothesis of a link between vaccination and a possible adverse outcome
      arises, further investigation is required to confirm or refute the suspicion.
      Given the rarity of most serious adverse effects, a case-control approach will
      often be chosen. This paper discusses aspects of the design, analysis and
      interpretation of case-control studies to evaluate vaccine adverse effects.
      Potential biases (and how to minimise such biases) in the selection of cases and
      assessment of vaccine exposure and the potential for confounding are discussed.
      Finally the increasing use of electronic databases in the evaluation of vaccine
      adverse effects is considered.

PMID- 12057621
TI  - Clinical and serological studies on CAM-70 live attenuated measles vaccine: an 18
      year survey at a pediatric clinic in Japan.
AB  - Live attenuated measles vaccine chorioallantonic membrane-70 (CAM-70) was
      administered to 471 healthy individuals over an 18-year period (1982-1999) at the
      pediatric clinic of Showa Hospital in Japan. Seroconversion occurred in 95.4%
      (418/438) of initially seronegative subjects. Reactions to the vaccine were
      generally insignificant, except for vaccine-related fever in about 20%. In
      February 2000, we made a questionnaire survey of 272 initially seronegative
      subjects who were vaccinated, from 0.7 to 18.1 years (mean: 5.5 years) earlier.
      Six (2.2%) of them contracted breakthrough measles during follow-up. The vaccine
      was generally safe and effective. However, it warrants investigation that the
      incidence of breakthrough measles may increase in the future in Japan.

PMID- 12057622
TI  - Comparative efficacy and immunogenicity of Q fever chloroform:methanol residue
      (CMR) and phase I cellular (Q-Vax) vaccines in cynomolgus monkeys challenged by
      aerosol.
AB  - Preliminary evidence gathered in rodents and livestock suggested that a phase I
      chloroform:methanol residue (CMR) extracted vaccine was safe and efficacious in
      protecting these animals from challenge with the obligate phagolysosomal pathogen
      (Coxiella burnetii). Prior to the initiation of phase II studies in human
      volunteers, we compared, in non-human primates (Macaca fascicularis), the
      efficacy of CMR vaccine with Q-Vax, a licensed cellular Australian Q fever
      vaccine that has been demonstrated to provide complete protection in human
      volunteers. Vaccine efficacy was assessed by evaluating thoracic radiographs and
      the presence of fever and bacteremia in monkeys challenged by aerosol with
      Coxiella burnetii. Changes in blood chemistries, hematology, behavior and
      pulmonary function were also examined. CMR, whether administered in single 30 or
      100 microg doses or two 30 microg subcutaneous doses, gave equivalent protection
      in vaccine recipients as a single 30 microg dose of Q-Vax. In addition,
      vaccination resulted in significant, although temporary, increases in specific
      antibody titers against C. burnetii phases I and II antigens. The C. burnetii CMR
      vaccine may be an efficacious alternative to cellular Q fever vaccines in humans.

PMID- 12057632
TI  - The recent impact of solid-phase synthesis on medicinally relevant benzoannelated
      nitrogen heterocycles.
AB  - Benzoannelated heterocycles such as benzodiazepines and indoles can be prepared
      efficiently through cyclization on solid supports, although no single approach is
      currently universal for the preparation of all benzoannelated N-heterocycle
      chemistries. In this review, a number of synthetic strategies for the generation
      of benzoannelated nitrogen heterocycles using resin-bound substrates have been
      described. Classical heterocycle forming reactions such as the Fischer indole,
      the Bischler-Napieralski tetrahydroisoquinoline, the Pictet-Spengler tetrahydro
      beta-carboline, the Tsuge, the Nenitzescu and the Richter cinnoline reaction are
      presented. In addition, the Heck, Sonogashira, Wittig, Diels-Alder, and olefin
      metathesis reactions have been also used. Multicomponent reactions such as the
      Grieco three-component assembly have been exploited for the synthesis of
      heterocycles. Cyclative cleavage from the solid support is particularly suitable
      for the synthesis of heterocycles while particular emphasis has been focused on
      the synthesis of libraries and the use of combinatorial chemistry techniques. In
      addition, the most relevant pharmacological properties of benzoannelated nitrogen
      heterocycles are included.

PMID- 12057633
TI  - Hydrazinocurcumin, a novel synthetic curcumin derivative, is a potent inhibitor
      of endothelial cell proliferation.
AB  - Curcumin and some of its derivatives were known as in vivo inhibitors of
      angiogenesis. In present study, a novel curcumin derivative, named
      hydrazinocurcumin (HC) was synthesized and examined for its biological
      activities. HC potently inhibited the proliferation of bovine aortic endothelial
      cells (BAECs) at a nanomolar concentration (IC(50)=520 nM) without cytotoxicity.
      In vivo and in vitro angiogenesis experiments showed HC as a new candidate for
      anti-angiogenic agent.

PMID- 12057634
TI  - Studies on scavenger receptor inhibitors. Part 1: synthesis and structure
      activity relationships of novel derivatives of sulfatides.
AB  - Scavenger receptors have been proven to be implicated in the formation of
      atherosclerotic lesions. A series of novel derivatives of sulfatides were
      synthesized, and their inhibitory activities against incorporation of DiI-acetyl
      LDL into macrophages were evaluated in order to clarify the structure-activity
      relationships of sulfatides as a scavenger receptor inhibitor and find out novel
      inhibitors with synthetic easiness. The chemical modification of the
      substructures of sulfatides led to the establishment of the following structure
      activity relationships; (1) the ceramide moiety can be replaced with another
      structure bearing two long chains, (2) the galactose moiety can be replaced with
      another structure or be deleted without a large decrease in the inhibitory
      activity, (3) the sulfate moiety was crucial, and it was the most preferable
      functional group for a potent inhibitory activity. The inhibitory activity of (S)
      2-octadecanoylamino-2-tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) against
      incorporation of DiI-acetyl-LDL into macrophages was proven to be based on the
      inhibition against the binding of acetyl-LDL to the surface of macrophages. We
      discovered novel scavenger receptor inhibitors with synthetic easiness, such as
      (S)-2-octadecanoylamino-2-(tetradecylcarbamoyl)ethyl sulfate sodium salt (3a) and
      2-octadecanoylamino-1-(octadecanoylaminomethyl)ethyl sulfate sodium salt (13q).

PMID- 12057635
TI  - 6-Carboxy-5,7-diarylcyclopenteno[1,2-b]pyridine derivatives: a novel class of
      endothelin receptor antagonists.
AB  - Compounds (2-5) with a 6-carboxy-5,7-diarylcyclopentenopyridine skeleton were
      designed, synthesized, and identified as a new class of potent non-peptide
      endothelin receptor antagonists. The regio-isomer 2 was found to show potent
      inhibitory activity with an IC(50) value of 2.4 nM against (125)I-labeled ET-1
      binding to human ET(A) receptors and a 170-fold selectivity for ET(A) over ET(B)
      receptors. Furthermore, 2 displayed more potent in vivo activity than did the
      indan-type compound 1 in a mouse ET-1 induced lethality model, suggesting the
      potential of 2 as a new lead structure. Derivatization on substituted phenyl
      groups at the 5- and 7-positions of 2 revealed that a 3,4-methylenedioxyphenyl
      group at the 5-position and a 4-methoxyphenyl group at the 7-position were
      optimal for binding affinity. Further derivatization of 2 by incorporating a
      substituent into the 2-position of the 4-methoxyphenyl group led to the
      identification of a more potent ET(A) selective antagonist 2p with an IC(50)
      value of 0.87 nM for ET(A) receptors and a 470-fold selectivity. In addition, 2p
      showed highly potent in vivo efficacy (AD(50): 0.04 mg/kg) in the lethality
      model.

PMID- 12057636
TI  - Computer-aided simulation of a dendrimer with a protoporphyrinic core as
      potential, novel hemoprotein mimic.
AB  - In this work, we have inserted the ion-heme group characterizing human blood in a
      class of synthetic, dendrimeric macromolecules, to evaluate a series of
      structural and physico-chemical properties related to the possible biological
      activity of these polymers. To this purpose, we have performed a complete series
      of investigations of five dendrimer generations both in vacuum and in water by
      molecular mechanics/dynamics simulations. To mimic oxygen binding, we have
      studied the same molecules in which the protoporphyrinic core was complexed to a
      Fe(II)-O(2)-hystidine residue. The main results of this study have led us to
      conclude that all dendrimer generations can bind oxygen stably, the fifth
      generation being the most affine to the myoglobin molecule, the natural carrier
      of blood oxygen.

PMID- 12057637
TI  - Deoxysarpagine hydroxylase--a novel enzyme closing a short side pathway of
      alkaloid biosynthesis in Rauvolfia.
AB  - Microsomal preparations from cell suspension cultures of the Indian plant
      Rauvolfia serpentina catalyze the hydroxylation of deoxysarpagine under formation
      of sarpagine. The newly discovered enzyme is dependent on NADPH and oxygen. It
      can be inhibited by typical cytochrome P450 inhibitors such as cytochrome c,
      ketoconazole, metyrapone, tetcyclacis and carbon monoxide. The CO-effect is
      reversible with light (450 nm). The data indicate that deoxysarpagine hydroxylase
      is a novel cytochrome P450-dependent monooxygenase. A pH optimum of 8.0 and a
      temperature optimum of 35 degrees C were determined. K(m) values were 25 microM
      for NADPH and 7.4 microM for deoxysarpagine. Deoxysarpagine hydroxylase activity
      was stable in presence of 20% sucrose at -25 degrees C for >3 months. The
      analysis of presence of the hydroxylase in nine cell cultures of seven different
      families indicates a very limited taxonomic distribution of this enzyme.

PMID- 12057638
TI  - Synthesis and D(2)-like binding affinity of new derivatives of N-(1-ethyl-2
      pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide and related 4H
      [1]benzothiopyrano[4,3-b]pyrrole and 5,6-dihydro-4H
      benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide analogues.
AB  - Various new derivatives and structural analogues of N-(1-ethyl-2
      pyrrolidinylmethyl)-4,5-dihydro-1H-benzo[g]indole-3-carboxamide (2a), a
      representative term of a series of 2-aminomethylpyrrolidinyl derived 4,5
      dihydrobenzo[g]indolcarboxamides with good D(2)-like affinity, were synthesized
      and evaluated for their ability to bind to dopamine D(2)-like receptors in vitro.
      The structural contribution to D(2)-like receptor binding of the 4,5
      dihydrobenzo[g]indole portion of the molecule was examined. From these studies,
      compound 2k, 2-chloro-N-(1-ethyl-2-pyrrolidinylmethyl)-5,6-dihydro-4H
      benzo[6,7]cyclohepta[b]pyrrole-3-carboxamide, was found to possess a potent
      affinity for D(2)-like receptors. Behavioural tests in rats have shown that this
      compound reduces the hyperactivity induced by amphetamine, a property shared by
      all antipsychotic drugs, at a dose which failed to induce catalepsy, an effect
      which is predictive of extrapyramidal side effects in humans. The other compounds
      demonstrated moderate (2c, 2h, and 2j) or no affinity for D(2)-like receptors.

PMID- 12057640
TI  - Design, synthesis and QSAR studies on N-aryl heteroarylisopropanolamines, a new
      class of non-peptidic HIV-1 protease inhibitors.
AB  - A series of N-aryl heteroarylisopropanolamines in which an indole or a 3
      arylpyrrole moiety was linked to an aryl group through an isopropanolamine
      linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series
      was tested for their ability in blocking PR activity. As a rule, indole
      derivatives of class 1 exhibited more potency than pyrrole analogues of class 2
      while tert-butylamide substituents increased anti-PR potency. In fact, bis tert
      butylamide 1e showed the highest activity with IC(50)=25 microM. Even if not very
      potent, a simple class of anti-PR agents, with a facile synthetic pathway was
      discovered. QSAR studies on isopropanolamines 1 and 2 were performed in
      comparison with diarylbutanols, a new class of non peptidic anti-PR agents,
      recently discovered by Agouron Pharmaceuticals. QSAR and CoMFA models based on 30
      diarylbutanols used as a training set were developed. The obtained models were
      used to investigate the binding mode of the newly synthesized derivatives 1 and
      2. The results of this study suggest that N-aryl heteroarylisopropanolamines bind
      to the PR active site similarly to the diarylbutanols of Agouron.

PMID- 12057639
TI  - Cysteinyl-flavan-3-ol conjugates from grape procyanidins. Antioxidant and
      antiproliferative properties.
AB  - New bio-based antioxidant compounds have been obtained by depolymerisation of
      grape polymeric flavanols in the presence of cysteine. Their preparation and
      purification, as well as their antiradical/antioxidant and antiproliferative
      properties are reported. 4beta-(S-cysteinyl)epicatechin 5, 4beta-(S
      cysteinyl)catechin 6 and 4beta-(S-cysteinyl)epicatechin 3-O-gallate 7 were
      efficiently purified from the crude depolymerised mixture by cation-exchange
      chromatography and preparative reversed-phase chromatography. The new compounds
      were more efficient than the underivatised (-)-epicatechin 1 as scavengers of the
      1,1-diphenyl-2-picrylhydrazyl free radical (DPPH) and weak growth inhibitors of
      human colon carcinoma HT29 cells. The order of antiradical and antiproliferative
      efficiency was 7 >5 approximately 6 >1, the same for both assays.

PMID- 12057641
TI  - Labdane-type diterpenes with inhibitory effects on increase in vascular
      permeability and nitric oxide production from Hedychium coronarium.
AB  - The methanolic extract from the rhizome of Hedychium coronarium was found to
      inhibit the increase in vascular permeability induced by acetic acid in mice and
      nitric oxide production in lipopolysaccharide-activated mouse peritoneal
      macrophages. From the methanolic extract, three new labdane-type diterpenes,
      hedychilactones A, B, and C, were isolated together with six known diterpenes.
      The structures of hedychilactones were elucidated on the basis of chemical and
      physicochemical evidence. The diterpene constituents showed inhibitory effects on
      the increase in vascular permeability, nitric oxide production, and inducible
      nitric oxide synthase induction.

PMID- 12057642
TI  - Piperidino-hydrocarbon compounds as novel non-imidazole histamine H(3)-receptor
      antagonists.
AB  - In search for novel non-imidazole histamine H(3)-receptor antagonists, piperidino
      hydrocarbon compounds were synthesized using the known non-imidazole histamine
      H(3)-receptor antagonist FUB 637 (3-phenylpropyl 3-piperidinopropyl ether) as
      lead structure. Piperidino-alkyl derivatives containing highly flexible side
      chains (2, 4-7) were prepared via N-alkylation. Compounds containing unsaturated
      alkyl groups were synthesized in order to investigate the impact of rigidifying
      the side chain (8-16). Terminal alkynes were prepared by alkylation of lithium
      acetylide-ethylenediamine complex, disubstituted alkynes were synthesized by
      alkylation of the appropriate acetylene in the presence of n-butyllithium
      N,N,N',N'-tetramethylene-ethylene-diamine complex. The novel compounds were
      investigated in an in vitro functional assay on the guinea-pig ileum, in which N
      (7-phenylhept-3-ynyl)piperidine (14) proved to be of good potency in this class
      (pA(2)=7.21). In an in vivo assay the compounds were additionally screened for
      their abilities to influence central H(3)-histaminergic neuron activity in mice
      with regard to their oral availabilities and distribution properties. In this
      screening, N-pent-4-ynylpiperidine (9) and N-hex-5-ynylpiperidine (10) proved to
      be highly potent and orally available histamine H(3)-receptor antagonists. The
      ED(50) values for 9 and 10 were 1.3 and 1.4mg/kg po, respectively, which is in
      the potency range of the reference antagonist thioperamide.

PMID- 12057644
TI  - Cleavage of beta-lactone ring by serine protease. Mechanistic implications.
AB  - Both enantiomers of 3-benzyl-2-oxetanone (1) were found to be slowly hydrolyzed
      substrates of alpha-chymotrypsin having k(cat) values of 0.134+/-0.008 and
      0.105+/-0.004 min(-1) for (R)-1 and (S)-1, respectively, revealing that alpha-CT
      is virtually unable to differentiate the enantiomers in the hydrolysis of 1. The
      initial step to form the acyl-enzyme intermediate by the attack of Ser-195
      hydroxyl on the beta-lactone ring at the 2-position in the hydrolysis reaction
      may not be enzymatically driven, but the relief of high ring strain energy of
      beta-lactone may constitute a major driving force. The deacylation step is also
      attenuated, which is possibly due to the hydrogen bond that would be formed
      between the imidazole nitrogen of His-57 and the hydroxyl group generated during
      the acylation in the case of (R)-1, but in the alpha-CT catalyzed hydrolysis of
      (S)-1 the imidazole nitrogen may form a hydrogen bond with the ester carbonyl
      oxygen.

PMID- 12057643
TI  - Fluorescent somatostatin receptor probes for the intraoperative detection of
      tumor tissue with long-wavelength visible light.
AB  - Targeted fluorescent dyes are of substantial value for the intraoperative
      delineation of primary tumors and metastatic lesions. For this purpose long
      wavelength red light (lambda=550-650 nm) offers advantages because of good tissue
      penetration and direct visibility. Since somatostatin receptors (SSTR) are
      overexpressed in a number of tumors, a series of potentially tumor-selective
      peptide-dye conjugates were synthesized by solid-phase peptide synthesis (SPPS).
      The octapeptides octreotate, Tyr(3)-octreotate and Tyr(3)-octreotide were
      employed and exhibited high affinity for somatostatin receptors (SSTR). The
      fluorescent dyes rhodamine 101, sulforhodamine B acid chloride, sulforhodamine
      101 or rhodamine B isothiocyanate were conjugated either directly or via spacers,
      for example the peptidase-labile pentapeptide sequence Ala-Leu-Ala-Leu-Ala. The
      conjugates were completely assembled on the solid support: Fmoc-SPPS, cyclization
      via a disulfide linkage, N-terminal attachment of a spacer, and linkage to the
      fluorescent dye. An in vitro competition assay revealed that the conjugates bind
      to SSTRs with IC(50) values between 0.7 and 89 nM. The conjugates were generally
      stable to hydrolysis at pH 7-8 in buffer or serum. However, the rhodamine 101
      conjugates revealed a loss of absorption at alkaline pH due to conversion to a
      neutral spirolactam form, as characterized by NMR.

PMID- 12057645
TI  - Bile acid derivatives of 5-amino-1,3,4-thiadiazole-2-sulfonamide as new carbonic
      anhydrase inhibitors: synthesis and investigation of inhibition effects.
AB  - Bile acid amides (cholan-24-amides) of 5-substituted 1,3,4-thiadiazole-2
      sulfonamide have been prepared from lithocholic, deoxycholic, cholic and
      dehydrocholic acids. Besides, the alcohol functional groups on the cholane ring
      systems were protected with acetyl group. Amides of the protected cholanes of
      lithocholic and cholic acids were also synthesized. Later, inhibition effects of
      these compounds on human carbonic anhydrase isozymes (HCA-I and II) have been
      investigated in vitro. For the most active compounds, inhibition constants ranged
      from 66 to 190nM for HCA-II with I(50) (molarity of inhibitor producing a 50%
      inhibition of CA activity). In addition, in vivo studies were performed for the
      synthesized compounds in Sprague-Dawley rats. The compounds (11 and 18) showed
      especially significant inhibition efficacy (p<0.001).

PMID- 12057646
TI  - Highly water-soluble matrix metalloproteinases inhibitors and their effects in a
      rat adjuvant-induced arthritis model.
AB  - A new series of succinate-based dual inhibitors against matrix metalloproteinases
      (MMPs) and tumor necrosis factor alpha converting enzyme (TACE) possessing highly
      water solubility was designed, synthesized, and evaluated for enzyme inhibition.
      Incorporating of acidic or basic functional groups at the P(2)' position afforded
      sufficient water solubility without significant loss of inhibitory potencies.
      Compound 18e, which had a guanidino group at the P(2)' position as the basic
      functional group, exhibited broad inhibition against target enzymes for a
      relatively long period in rat plasma (beta t(1/2); 2.0h) after sc administration
      when compared with compounds possessing acidic functional groups (18a and 18b).
      Consequently, the representative compound 18e together with compound 18b,
      Marimastat and Trocade were evaluated in the rat adjuvant-induced arthritis
      model, a model of chronic cartilage destruction. It is concluded that the newly
      synthesized highly water-soluble compound 18e showed significant activity in
      suppressing hindpaw swelling and the bone destruction with a minimal
      administration period (days 3-7).

PMID- 12057647
TI  - Some aspects of NaBH(4) reduction in NMP.
AB  - In our solvent optimization study of NaBH(4) reduction, NMP was found to enhance
      the reactivity. A chemoselective debromination of the bromide and sulfonates can
      be attained in the new borohydride reagent system: NaBH(4)-LiOTf-NMP. This mixed
      system worked as an alternative to NaBH(3)CN and Bu(3)SnH for the S(N)2 type
      displacement of alkylbromide and sulfonate. Also mentioned is an expedient
      reduction of an azide group into amine by NaBH(4) in NMP without any additive,
      which offers a convenient protocol for the direct transformation of halides into
      amines via azide in one flask. Some examples of other reductions were also
      presented.

PMID- 12057648
TI  - Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and
      their potent activity against Candida species.
AB  - New 2-substituted-phenyl-1H-benzimidazole-5-carboxylic acids (35, 38), ethyl-5
      carboxylate (36), -5-carboxamides (37, 39),-5-carboxaldehyde (42), -5-chloro
      (40), -5-trifluoromethyl (41), and -5-carbonitriles (44-53, 55-67), -6
      carbonitrile (54) were prepared and evaluated in vitro against Candida species.
      The cyano substituted compounds 53, 57, 58 and 61 exhibited the greatest activity
      with MIC values of 3.12 microg/mL, values similar to that of fluconazole.

PMID- 12057649
TI  - Design, synthesis and biological activity of YM-60828 derivatives: potent and
      orally-bioavailable factor Xa inhibitors based on naphthoanilide and
      naphthalensulfonanilide templates.
AB  - Factor Xa (FXa) is a serine protease which plays a pivotal role in the
      coagulation cascade. The inhibition of FXa has received great interest as a
      potential target for the development of new antithrombotic drug. Herein we
      describe a series of novel 7-amidino-2-naphthoanilide and 7-amidino-2
      naphthalensulfonanilide derivatives which are potent FXa inhibitors. These
      scaffolds are rigid and are allowed to adopt an L-shape conformation which was
      estimated as the active conformation based on a docking study of YM-60828 with
      FXa. Optimization of the side chain at the central aniline nitrogen of 7-amidino
      2-naphthoanilide has led to several potent and orally active FXa inhibitors. 5h
      (YM-169964), the best compound of these series, showed potent FXa inhibitory
      activity (IC(50)=3.9nM) and effectively prolonged prothrombin time by 9.6-fold ex
      vivo at an oral dose of 3mg/kg in squirrel monkeys.

PMID- 12057650
TI  - Synthesis of a fluorine-18-labelled derivative of 6-nitroquipazine, as a
      radioligand for the in vivo serotonin transporter imaging with PET.
AB  - Considerable efforts have been engaged in the design, synthesis and
      pharmacological characterization of radioligands for imaging the serotonin
      transporter, based on its implication in several neuropsychiatric diseases, such
      as depression, anxiety and schizophrenia. In the 5-halo-6-nitroquipazine series,
      the fluoro derivative has been designed for positron emission tomography (PET).
      The corresponding 5-iodo-, 5-bromo- and 5-chloro N-Boc-protected quipazines as
      labelling precursors, as well as 5-fluoro-6-nitroquipazine as a reference
      compound have been synthesized. 5-[(18)F]Fluoro-6-nitroquipazine has been
      radiolabelled with fluorine-18 (positron-emitting isotope, 109.8 min half-life)
      by nucleophilic aromatic substitution from the corresponding N-Boc protected 5
      bromo- and 5-chloro-precursors using K[(18)F]F-K(222) complex in DMSO by
      conventional heating (145 degrees C, 2 min) or microwave activation (50 W, 30-45
      s), followed by removal of the protective group with TFA. Typically, 15-25 mCi
      (5.5-9.2 GBq) of 5-[(18)F]fluoro-6-nitroquipazine (1-2 Ci/micromol or 37-72
      GBq/micromol) could be obtained in 70-80 min starting from a 550-650 mCi (20.3
      24.0 GBq) aliquot of a cyclotron [(18)F]F(-) production batch (2.7-3.8% non decay
      corrected yield based on the starting [(18)F]fluoride). Ex vivo studies
      (biodistribution in rat), as well as PET imaging (in monkey) demonstrated that 5
      [(18)F]fluoro-6-nitroquipazine ([(18)F]-1d) readily crossed the blood brain
      barrier and accumulated in the regions rich in 5-HT transporter (frontal- and
      posterial cortex, striata). However, the low accumulation of the tracer in the
      thalamus (rat and monkey) as well as the comparable displacement of the tracer
      observed with both citalopram, a -HT re-uptake inhibitor and maprotiline, a
      norepinephrine re-uptake inhibitor (rat), indicate that 5-[(18)F]fluoro-6
      nitroquipazine ([(18)F]-1d) does not have the suggested potential for PET imaging
      of the serotin transporter (SERT).

PMID- 12057651
TI  - Synthesis and analysis of urea and carbamate prodrugs as candidates for
      melanocyte-directed enzyme prodrug therapy (MDEPT).
AB  - The suitability of 4-di(2-chloroethyl)aminoanilino-4
      hydroxyphenethylaminomethanone 2 to act as a prodrug for melanocyte-directed
      enzyme prodrug therapy (MDEPT) is assessed. Thus its synthesis, ability to
      generate a cytotoxic agent upon exposure to tyrosinase, and stability within
      different sera are reported. A comparison is made to illustrate that the new urea
      prodrug 2 is a more suitable candidate for MDEPT than the corresponding carbamate
      prodrug 1.

PMID- 12057652
TI  - Detection of protein-ligand interaction on the membranes using C-terminus biotin
      tagged alamethicin.
AB  - C-terminal biotin-tagged alamethicin, which has several alpha-aminoisobutyric
      acid (Aib) residues in its sequence, was synthesized by the preparation of the
      protected peptide segment using the 2-chlorotrityl resin, followed by conjugation
      with biotin hydrazide. Suppression of the channel current of the biotin-tagged
      alamethicin by the addition of streptavidin to the electrolyte was monitorable in
      real time using the planar lipid-bilayer method. The system was also applicable
      to the detection of interaction of the biotin-tagged alamethicin with the anti
      biotin antibody.

PMID- 12057653
TI  - Identification of novel mammalian squalene synthase inhibitors using a three
      dimensional pharmacophore.
AB  - Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerisation of
      farnesyl diphosphate in a [1-4] head to head fashion to form squalene, and is the
      first committed step in cholesterol biosynthesis. Specific inhibitors of squalene
      synthase would inhibit cholesterol formation and allow production of other
      important compounds derived from the cholesterol biosynthetic pathway, namely the
      ubiquinones (co-enzyme Q(10)), dolichol, and would also allow the isoprenylation
      process of ras by farnesyl-protein transferase. The construction of a
      hypothetical squalene synthase three-dimensional pharmacophore is presented. It
      serves as a template for the identification of several new potential classes of
      inhibitors. The synthesis, anti-microbial and mammalian pig liver squalene
      synthase activities of analogues based on the bicyclo[3.2.0]heptane and
      bicyclo[3.3.0]octane ring systems are reported. Analogues of the latter system
      are pro-drug type inhibitors and exhibit promising biological activity.

PMID- 12057654
TI  - Non-thiol farnesyltransferase inhibitors: utilization of an aryl binding site by
      5-arylacryloylaminobenzophenones.
AB  - We recently described a novel aryl binding site of farnesyltransferase. The 2
      naphthylacryloyl residue was developed as an appropriate substituent for our
      benzophenone-based AAX-peptidomimetic capable of occupying this binding site,
      resulting in a non-thiol farnesyltransferase inhibitor with nanomolar activity.
      The activity of this inhibitor is readily explained on the basis of docking
      studies which show the 2-naphthyl residue fitting into the aryl binding site.

PMID- 12057655
TI  - Synthesis and vasorelaxant activity of new 1,4-benzoxazine derivatives potassium
      channel openers.
AB  - As part of a search for new potassium channel openers, the synthesis and
      vasorelaxant activity of new 1,4-benzoxazine derivatives derived from
      transformation of the benzopyran skeleton of cromakalim were described. Several
      new 1,4-benzoxazine derivatives were provided with significant vasorelaxant
      activity with an overall pharmacological behavior similar to CRK (1f, 1i, 2d, 2e,
      2f and 2i).

PMID- 12057656
TI  - Synthesis and biological activity of novel pyrimidinone containing
      thiazolidinedione derivatives.
AB  - A series of pyrimidinone derivatives of thiazolidinediones were synthesized.
      Their biological activity were evaluated in insulin resistant, hyperglycemic and
      obese db/db mice. In vitro PPARgamma transactivation assay was performed in HEK
      293T cells. PMT13 showed the best biological activity in this series. PMT13 (5-[4
      [2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1
      pyrimidinyl]ethoxy]phenylmethyl]thiazolidine-2,4-dione) showed better plasma
      glucose, triglyceride and insulin-lowering activity in db/db mice than
      rosiglitazone and pioglitazone. PMT13 showed better PPARgamma transactivation
      than the standard compounds. Pharmacokinetic study in Wistar rats showed good
      systemic exposure of PMT13. Twenty-eight day oral toxicity study in Wistar rats
      did not show any treatment-related adverse effects.

PMID- 12057657
TI  - Novel potent 5-HT(3) receptor ligands based on the pyrrolidone structure. Effects
      of the quaternization of the basic nitrogen on the interaction with 5-HT(3)
      receptor.
AB  - The results of a comprehensive structure-affinity relationship study on the
      effect of the quaternization (i.e., N-methylation) of structurally different
      ligands in the classes of tropane and quinuclidine derivatives are described.
      This study shows that the effects of the quaternization of the basic nitrogen of
      these 5-HT(3) receptor ligands appear to be strictly structure-dependent
      suggesting that different binding modes are operative at 5-HT(3) receptor binding
      site. The different effect of the quaternization of the basic nitrogen of
      structurally different ligands were rationalized in terms of the interaction with
      the receptor by means of the combined use of experimental techniques (X-ray
      diffraction and NMR studies) and computational simulation studies.

PMID- 12057659
TI  - Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro
      quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives.
AB  - Certain indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones 4a,b, 6, 8, 16a-c
      and 6-anilinoindoloquinoline derivatives 10a,b, 11a,b, 12a,b have been
      synthesized and evaluated in vitro against a 3-cell lines panel consisting of
      MCF7 (Breast), NCI-H460 (Lung), and SF-268 (CNS). Those active compounds 4a,b, 6,
      8, 10a,b, 11a,b, 12a,b were then evaluated in the full panel of 60 human tumor
      cell lines derived from nine cancer cell types. The results have shown that
      cytotoxicity decreases in the order of 6-anilinoindoloquinolines>indoloquinolin
      2(1H)-ones>pyrroloquinolin-2(1H)-ones>benzofuroquinolin-2(1H)-ones. Among them, 1
      [3-(11H-indolo[3,2-c]quinolin-6ylamino)phenyl]ethanone oxime hydrochloride (11a)
      and its 2-chloro derivative (11b) were most active, with mean GI(50) values of
      1.70 and 1.35 microM, respectively. Both compounds 11a,b were also found to
      inhibit the growth of SNB-75 (CNS cancer cell) with a GI(50) value of less than
      0.01 microM, and, therefore, were selected for further evaluation for in vivo
      antitumor activity.

PMID- 12057658
TI  - Synthesis, characterization and antitumor studies of transition metal complexes
      of o-hydroxydithiobenzoate.
AB  - o-Hydroxydithiobenzoate (o-HOdtb) forms complexes, [Ni(o-HOdtb)(o-HOdtbS)], [Cu(o
      Odtb)], [Co(o-HOdtb)(3)], [Fe(2)(o-Odtb)(3)], [Bu(n)(4)N][V(o-Odtb)(3)] and
      [Bu(n)(4)N][Zn(o-HOdtb)(3)] which were characterized by analyses and
      physicochemical studies. The bonding sites of o-HOdtb and the geometry of the
      complexes were determined by magnetic susceptibility, IR, ESR, NMR, Mossbauer and
      electronic spectral data. The structure of [Bu(n)(4)N][Zn(o-HOdtb)(3)] and
      H(2)C(o-HOdtb)(2) were assigned by single crystal X-ray diffraction studies. The
      monomeric complex [Bu(n)(4)N][Zn(o-HOdtb)(3)] crystallizes in Pna2(1) space
      group. The Mossbauer spectra of [Fe(2)(o-Odtb)(3)] at 298 and 80K suggest the
      presence of high spin iron(III) with an S=5/2 state. All the metal complexes were
      observed to inhibit the growth of tumor in vitro, whereas, ligand did not. In
      vivo administration of these complexes resulted in prolongation of survival of
      tumor-bearing mice. Tumor bearing mice administered with metal complexes showed
      reversal of tumor growth associated induction of apoptosis in lymphocytes. The
      paper discusses the possible mechanisms and therapeutic implication of the ligand
      and its metal complexes in tumor regression and tumor growth associated
      immunosuppression.

PMID- 12057660
TI  - Synthesis and antirheumatic activity of the metabolites of esonarimod.
AB  - We have developed esonarimod, (+/-)-2-acetylthiomethyl-4-(4-methylphenyl)-4
      oxobutanoic acid, as a new antirheumatic drug. Now we describe herein the
      preparation of the enantiomers of (+/-)-deacetylesonarimod, the pharmaceutically
      active metabolites of esonarimod, and comparison of their antirheumatic
      activities. No significant difference has been observed between the two
      enantiomers. In a pre-clinical study of esonarimod, other metabolites were
      detected in rat blood or urine. We also synthesized these compounds as authentic
      samples to analyze the human metabolites in clinical studies of esonarimod.

PMID- 12057661
TI  - Is the anomeric effect an important factor in the rate of adenosine deaminase
      catalyzed hydrolysis of purine nucleosides? A direct comparison of nucleoside
      analogues constructed on ribose and carbocyclic templates with equivalent
      heterocyclic bases selected to promote hydration.
AB  - The aglycone of (North)-methanocarbadeoxyadenosine [(N)-MCdA, (5)], a relatively
      weak substrate for adenosine deaminase (ADA)-relative rate of deamination ca. 100
      times lower than adenosine-was modified with substitutions at positions 6 (6
      fluoro, compound 6) and 8 (8-aza, compound 7) with the intent to improve the
      level of hydration and hence hydrolysis by ADA. In these substrates the fused
      cyclopropane moiety constrains the cyclopentane ring to mimic the conformation of
      a furanose sugar in the North hemisphere of the pseudorotational cycle, which
      matches the conformation of the ribose ring of adenosine in complex with ADA. The
      order of susceptibility to ADA hydrolysis was adenosine>>(N)-MCdA (5)
      approximately equal to(N)-6F-MCdP (6)>(N)-8-aza-MCdA (7). Despite the known fact
      that 8-azaadenosine is hydrolyzed twice as fast as adenosine, the corresponding
      carbocyclic analogue 7 was hydrolyzed at approximately half the rate of the
      parent 5. These results argue in favor of the critical role of the O(4') oxygen
      atom and its associated anomeric effect in assisting hydrolysis by ADA.

PMID- 12057662
TI  - Synthesis and preliminary pharmacological evaluation of new (+/-) 1,4
      naphthoquinones structurally related to lapachol.
AB  - Seven new 1,4-naphthoquinones structurally related to lapachol were synthesized
      from lawsone and oxygenated arylmercurials. These compounds can also be seen as
      pterocarpan derivatives where the A-ring was substituted by the 1,4
      naphthoquinone nucleus. Pharmacological screening provided evidence of
      significant biological activities, including effects against proliferation of the
      MCF-7 human breast cancer cell line, against Herpes Simplex Virus type 2
      infection, and against snake poison-induced myotoxicity. One derivative displaced
      flunitrazepam binding and showed benzodiazepine-like activity, suggesting novel
      neuroactive structural motifs.

PMID- 12057663
TI  - 10-Formyl-5,10-dideaza-acyclic-5,6,7,8-tetrahydrofolic acid (10-formyl-DDACTHF):
      a potent cytotoxic agent acting by selective inhibition of human GAR Tfase and
      the de novo purine biosynthetic pathway.
AB  - The synthesis of 10-formyl-DDACTHF (3) as a potential inhibitor of glycinamide
      ribonucleotide transformylase (GAR Tfase) and aminoimidazole carboxamide
      ribonucleotide transformylase (AICAR Tfase) is reported. Aldehyde 3, the
      corresponding gamma- and alpha-pentaglutamates 21 and 25 and related agents were
      evaluated for inhibition of folate-dependent enzymes including GAR Tfase and
      AICAR Tfase. The inhibitors were found to exhibit potent cytotoxic activity (CCRF
      CEM IC(50) for 3=60nM) that exceeded their enzyme inhibition potency [K(i) (3)=6
      and 1 microM for Escherichia coli GAR and human AICAR Tfase, respectively].
      Cytotoxicity rescue by medium purines, but not pyrimidines, indicated that the
      potent cytotoxic activity is derived from selective purine biosynthesis
      inhibition and rescue by AICAR monophosphate established that the activity is
      derived preferentially from GAR versus AICAR Tfase inhibition. The potent
      cytotoxic compounds including aldehyde 3 lost activity against CCRF-CEM cell
      lines deficient in the reduced folate carrier (CCRF-CEM/MTX) or
      folylpolyglutamate synthase (CCRF-CEM/FPGS(-)) establishing that their potent
      activity requires both reduced folate carrier transport and polyglutamation.
      Unexpectedly, the pentaglutamates displayed surprisingly similar K(i)'s versus E.
      coli GAR Tfase and only modestly enhanced K(i)'s versus human AICAR Tfase. On the
      surface this initially suggested that the potent cytotoxic activity of 3 and
      related compounds might be due simply to preferential intracellular accumulation
      of the inhibitors derived from effective transport and polyglutamation (i.e., ca.
      100-fold higher intracellular concentrations). However, a subsequent examination
      of the inhibitors against recombinant human GAR Tfase revealed they and the
      corresponding gamma-pentaglutamates were unexpectedly much more potent against
      the human versus E. coli enzyme (K(i) for 3, 14nM against rhGAR Tfase versus 6
      microM against E. coli GAR Tfase) which also accounts for their exceptional
      cytotoxic potency.

PMID- 12057664
TI  - Effect of protonation of the N-acetyl neuraminic acid residue of sialyl Lewis(X):
      a molecular orbital study with insights into its binding properties toward the
      carbohydrate recognition domain of E-selectin.
AB  - Semiempirical molecular orbital (MO) calculations with an implicit treatment of
      the water environment were employed in order to assess whether the sialyl
      Lewis(X) (sLe(X)) tetrasaccharide binds to E-selectin in the anionic or neutral
      (i.e., protonated) state. The analysis of the frontier molecular orbitals,
      electrostatic potential surfaces, and conformational behavior of the sugar
      indicates that its neutral form possesses the necessary characteristics for
      binding. In particular, the LUMO level of the neutral sLe(X) molecule is
      localized both on the carboxylic group of the N-acetyl neuraminic acid (NeuNAc)
      residue and on the nearby glycosidic linkage. These two moieties interact with
      the Arg97 residue of E-selectin, as revealed by a recent crystal structure
      analysis of the E-selectin/sLe(X) complex. The energetics of this specific
      interaction was investigated with the aid of ab initio Hartree-Fock MO
      calculations, which resulted in a BSSE-corrected binding energy of 16.63
      kcal/mol. Our observations could open up new perspectives in the design of sLe(X)
      mimics.

PMID- 12057665
TI  - Probing the proposed phenyl-A region of the sigma-1 receptor.
AB  - The proposed phenyl-A region of sigma (sigma) receptors accommodates several
      structural features. In this study we explored the possibility that appropriate
      structural features located at the phenyl-A region of sigma receptor sites could
      lead to more potent and selective agents for the sigma receptor subtypes. By
      keeping the phenyl-B substituent as the optimum omega-phenylpentyl moiety, and
      varying substituents in the phenyl-A region, we have observed changes in binding
      potency and selectivity at the sigma receptor subtypes. SAR for the binding of
      these compounds at sigma-2 sites was also examined.

PMID- 12057666
TI  - Solid-phase synthesis of DNA binding polyamides on oxime resin.
AB  - Control of the energetics and specificity of DNA binding polyamides is necessary
      for inhibition of protein-DNA complex formation and gene regulation studies.
      Typically, solid-phase methods using Boc monomers for synthesis have depended on
      Boc-beta-Ala-PAM resin which affords a beta-alanine-Dp tail at the C-terminus,
      after cleavage with N,N-dimethylaminopropylamine (Dp). To address the energetic
      consequences of this tail for DNA minor groove binding, we describe an
      alternative solid phase method employing the Kaiser oxime resin which allows the
      synthesis of polyamides with incrementally shortened C-terminal tails. Polyamides
      without Dp and having methyl amide tails rather than beta-alanine show similar
      affinity relative to the standard beta-Dp tail. The truncated tail diminishes the
      A,T base pair energetic preference of the beta-Dp tail which will allow a greater
      variety of DNA sequences to be targeted by hairpin polyamides.

PMID- 12057667
TI  - Structure-based 3-D-QSAR analysis of marine indole alkaloids.
AB  - A 3-D-QSAR study has been performed on these indole alkaloid derivatives to
      correlate their chemical structures with their observed antitumor activity
      against IGROV1. Due to the absence of information on their active mechanism,
      comparative molecular field analysis (CoMFA) has been applied. A model able to
      well correlate the antitumor activity with the chemical structures of mono and
      bis(indole) alkaloids 1-18 has been developed which is potentially helpful in the
      design of novel and more potent antitumor agents.

PMID- 12057668
TI  - Synthesis and in vitro platelet aggregation and TP receptor binding studies on
      bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines.
AB  - Eighteen novel bicyclic 1-substituted benzyl octahydro- and
      tetrahydroisoquinolines were synthesized and evaluated for human thromboxane
      A(2)/prostaglandin H(2) (TP) receptor affinity and antagonism of TP receptor
      mediated platelet aggregation. In both cases, potency depended more on the
      presence of methoxy groups on the 1-benzyl moiety than on nitrogen substitution
      or extent of oxidation of the isoquinoline ring system. The most potent of the
      bicyclic compounds retained the 5,8-ethanooctahydroisoquinoline ring structure of
      the parent molecule (1) and required the 3,4,5-trimethoxybenzyl substitution
      pattern found in the well-characterized tetrahydroisoquinoline antiplatelet agent
      trimetoquinol. Differences in nitrogen substituent SAR were noted between the
      mono-methoxylated compounds and the 3,4,5-trimethoxybenzyl derivatives.

PMID- 12057669
TI  - Chalcones and flavonoids as anti-tuberculosis agents.
AB  - A series of flavonoids, chalcones and chalcone-like compounds were evaluated for
      inhibitory activity against Mycobacterium tuberculosis H37Rv. Among them, eight
      compounds exhibited >90% inhibition on the growth of the bacteria at a
      concentration of 12.5 microg/mL. Chalcones 1-(2-hydroxyphenyl)-3-(3-chlorophenyl)
      2-propen-1-one (22) and 1-(2-hydroxyphenyl)-3-(3-iodophenyl)-2-propen-1-one (37)
      demonstrated 90 and 92% inhibition, respectively. Chalcone-like compounds
      (heterocyclic ring-substituted 2-propen-1-one) 1-(4-fluorophenyl)-3-(pyridin-3
      yl)-2-propen-1-one (48), 1-(3-hydroxyphenyl)-3-(phenanthren-9-yl)-2-propen-1-one
      (49), 1-(pyridin-3-yl)-3-(phenanthen-9-yl)-2-propen-1-one (50) and 1-(furan-2-yl)
      3-phenyl-2-propen-1-one (51) exhibited 98, 97, 96 and 96% inhibition,
      respectively. The actual minimum inhibitory concentrations (MIC), defined as the
      lowest concentration inhibiting 99% of the inoculum, for 22, 37, 48, 49, 50 and
      51 were 20.3, 31.5, 48.3, >35.7, 6.8 and 19.2, respectively. A hydrophobic
      substituent on one aromatic ring, and a hydrogen-bonding group on the other
      aromatic ring resulted in increased anti-TB activity of the chalcones and
      chalcone-like compounds. Flavones and flavanones are more geometrically
      constrained than the corresponding chalcone analogues. The decreased activity of
      the flavones with respect to the chalcones may be due to the confinement of the
      terminal aromatic rings to the same plane.

PMID- 12057670
TI  - X-ray crystallographic structure of ABT-378 (lopinavir) bound to HIV-1 protease.
AB  - The crystal structure of ABT-378 (lopinavir), bound to the active site of HIV-1
      protease is described. A comparison with crystal structures of ritonavir, A
      78791, and BILA-2450 shows some analogous features with previous reported
      compounds. A cyclic urea unit in the P(2) position of ABT-378 is novel and makes
      two bidentate hydrogen bonds with Asp 29 of HIV-1 protease. In addition, a
      previously unreported shift in the Gly 48 carbonyl position is observed. A
      discussion of the structural features responsible for its high potency against
      wild-type HIV protease is given along with an analysis of the effect of active
      site mutations on potency in in vitro assays.

PMID- 12057671
TI  - Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of
      anti-HIV agents.
AB  - Substituted diarylmethylenepiperidines (DAMPs) were synthesized as
      conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of
      non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the
      ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM
      SS cells, they were completely inactive as inhibitors of HIV-1 reverse
      transcriptase. The DAMPs were assessed for inhibition of HIV attachment and
      fusion. DAMP was active in both assays with IC(50) values of 26.5 microM (TI 3.8)
      and 12.1 microM (TI: >8), respectively. DAMP also inhibited HIV fusion with an
      IC(50 )12.8 microM (TI: >6), but not virus attachment. However, attempts to
      verify inhibition of virus attachment and fusion as antiviral targets using time
      of-addition experiments failed to confirm these observations, and instead
      identified an antiviral target occurring after completion of reverse
      transcription. DAMPs, and were found to inhibit virus replication if added 8 h
      post virus exposure, and DAMP was equipotent at inhibition of virus replication
      if added 24 h after virus addition. DAMPs, and did not inhibit virus replication
      in TNF-alpha induced latently infected U1 cells, a model for post-integrative
      antiviral targets. When tested in both 3' end-processing and strand-transfer
      assays in the presence of HIV-1 integrase, none of the DAMPs showed any
      inhibitory activity, indicating that HIV-1 integrase is not involved in the
      mechanism of the antiviral action. Thus, the DAMPs are novel conformationally
      restricted analogues of the previously published ADAM series with an unidentified
      antiviral target bounded by the completion of reverse transcription and virus
      integration.

PMID- 12057675
TI  - Ecology and industrial microbiology: Microbial diversity - sustaining the Earth
      and industry.

PMID- 12057676
TI  - Microbial diversity and function in soil: from genes to ecosystems.
AB  - Soils sustain an immense diversity of microbes, which, to a large extent, remains
      unexplored. A range of novel methods, most of which are based on rRNA and rDNA
      analyses, have uncovered part of the soil microbial diversity. The next step in
      the era of microbial ecology is to extract genomic, evolutionary and functional
      information from bacterial artificial chromosome libraries of the soil community
      genomes (the metagenome). Sophisticated analyses that apply molecular
      phylogenetics, DNA microarrays, functional genomics and in situ activity
      measurements will provide huge amounts of new data, potentially increasing our
      understanding of the structure and function of soil microbial ecosystems, and the
      interactions that occur within them. This review summarizes the recent progress
      in studies of soil microbial communities with focus on novel methods and
      approaches that provide new insight into the relationship between phylogenetic
      and functional diversity.

PMID- 12057677
TI  - Polychlorinated biphenyl-degrading microbial communities in soils and sediments.
AB  - Recent advances in the degradation of polychlorinated biphenyls (PCBs) have
      focussed on the use of experimental enrichment cultures to obtain PCB-degrading
      communities, and the use of culture-independent approaches to characterize
      natural and experimental PCB-degrading communities and to identify the key
      members in this process. PCB-degrading communities can be surprisingly diverse.
      Novel types of composite bacteria-mineral biofilm communities have been
      described. Community metabolism of PCBs may lead to the formation of
      protoanemonin, a dead-end product in some instances but, in others, a seemingly
      productive intermediate. Analysis of isotope fractionation and preferred
      enantiomer degradation has provided new information on degradation of PCBs in
      anaerobic settings. The first defined community capable of dehalorespiration of
      PCBs has been described, and important community members identified. Here, we
      provide an overview of the current knowledge of aerobic and anaerobic degradation
      of PCBs in microbial consortia and in the environment, including novel approaches
      to determine in situ PCB degradation.

PMID- 12057678
TI  - Is there a role for quorum sensing signals in bacterial biofilms?
AB  - Bacteria form multicellular biofilm communities on most surfaces. Genetic
      analysis of biofilm formation has led to the proposal that extracellular signals
      and quorum-sensing regulatory systems are essential for differentiated biofilms.
      Although such a model fits the concept of density-driven cell-cell communication
      and appear to describe biofilm development in several bacterial species and
      conditions, biofilm formation is multifactorial and complex. Hydrodynamics,
      nutrient load and intracellular carbon flux have major impacts, presumably by
      altering the expression of cellular traits essential for bacterial adaptation
      during the different stages of biofilm formation. Hence, differentiated biofilms
      may also be the net result of many independent interactions, rather than being
      determined by a particular global quorum sensing system.

PMID- 12057679
TI  - Bioreporters in microbial ecology.
AB  - Bioreporters are effective research tools for gaining an understanding of a
      microbe's perception of the world. Fitted with a fusion of an environmentally
      responsive promoter to a suitable reporter gene, a bacterial or fungal
      bioreporter is able to communicate its metabolic or transcriptional behavior in a
      habitat, and furnish us with information on the chemical, physical or biological
      properties of its immediate surroundings. This review details recent developments
      in the use of such bioreporters in microbial ecology. Emphasis is placed on
      reporter genes that allow detection in individual microbial cells, as they
      provide a high-resolution description of the habitat under investigation. In an
      outlook on the future of bioreporter technology, this review stresses the need to
      interpret the activity of a bioreporter within the context of its biology.

PMID- 12057680
TI  - Bacterial chemotaxis to pollutants and plant-derived aromatic molecules.
AB  - There is accumulating evidence that motile bacteria are chemotactically attracted
      to environmental pollutants that they can degrade. Chemotaxis, the ability of
      motile bacteria to detect and respond to specific chemicals in the environment,
      can increase an organism's chances of locating useful sources of carbon, nitrogen
      and energy, and could thus play an important role in the biodegradation process.
      Recent evidence demonstrating that chemotaxis and biodegradation genes are
      coordinately regulated suggests that these processes are intimately linked in
      nature.

PMID- 12057681
TI  - Microbial transformation of alkaloids.
AB  - Alkaloids continue to provide mankind with a plethora of medicines, poisons and
      potions. Because many valuable drugs are derived from such natural compounds,
      there is much interest in their transformation to provide new compounds or
      intermediates for the synthesis of new or improved drugs. This review aims to
      provide a survey of alkaloid transformations, and concerns microbial
      transformations and microbially expressed recombinant plant enzymes and their
      biotechnological applications.

PMID- 12057682
TI  - Bioelimination of trinitroaromatic compounds: immobilization versus
      mineralization.
AB  - Electron deficiency of trinitroaromatic compounds favors gratuitous reduction of
      nitro groups or unique ring hydrogenation. From nitro-group reduction of 2,4,6
      trinitrotoluene (TNT), some highly reactive products are generated that are
      subject to further transformation or interaction with diverse electrophiles. Up
      to now, only initial ring hydrogenation of picric acid (2,4,6-trinitrophenol)
      opens perspectives of complete degradation. This review focuses on recent
      findings that may be relevant for bioremediation or complete degradation of TNT
      or picric acid.

PMID- 12057683
TI  - Bacterial detoxification of organophosphate nerve agents.
AB  - Bacterial enzymes have been isolated that catalyze the hydrolysis of
      organophosphate nerve agents with high-rate enhancements and broad substrate
      specificity. Mutant forms of these enzymes have been constructed through rational
      redesign of the active-site binding pockets and random mutagenesis to create
      protein variants that are optimized for the detoxification of agricultural
      insecticides and chemical warfare agents. In this review, the catalytic
      properties of two bacterial enzymes, phosphotriesterase and organophosphorus
      anhdrolase, are examined for their ability to hydrolyze organophosphate nerve
      agents.

PMID- 12057684
TI  - Microbial metal-ion reduction and Mars: extraterrestrial expectations?
AB  - Dissimilatory metal-ion-reducing bacteria (DMRB) can couple the reduction of a
      variety of different metal ions to cellular respiration and growth. The
      excitement of this metabolic group lies not only in the elucidation of a new type
      of metabolism, but also in the potential use of these abilities for the removal
      of toxic organics, and in their ability to reduce (and thus, detoxify) other
      toxic metals, such as U(VI) and Cr(VI). This review focuses on recent advances in
      the study of DMRB, including the use of external electron shuttles to enhance
      rates of metal reduction; genome sequencing and consequent genomic and proteomic
      analyses; new imaging approaches for high resolution analysis of both cells and
      chemical components; the demonstration of fractionation of stable isotopes of
      iron during iron reduction; and the elucidation of the types and patterns of
      secondary mineral formation during metal reduction. One of the secondary minerals
      is magnetite, the subject of intense controversy regarding the possibility of
      evidence for life from the Martian meteorite ALH84001. This review thus ends with
      a short consideration of the evidence for magnetic 'proof' of the existence of
      past life on Mars.

PMID- 12057685
TI  - Psychrophiles and polar regions.
AB  - Most reviews of microbial life in cold environments begin with a lament of how
      little is known about the psychrophilic (cold-loving) inhabitants or their
      specific adaptations to the cold. This situation is changing, as research becomes
      better focused by new molecular genetic (and other) approaches, by awareness of
      accelerated environmental change in polar regions, and by strong interest in the
      habitability of frozen environments elsewhere in the solar system. This review
      highlights recent discoveries in molecular adaptation, biodiversity and microbial
      dynamics in the cold, along with the concept of eutectophiles, organisms living
      at the critical interface inherent to the phase change of water to ice.

PMID- 12057687
TI  - Functional genomics as applied to mapping transcription regulatory networks.
AB  - The sequencing of the human genome and the entire genomes of many model organisms
      has resulted in the identification of many genes. Many large-scale experiments
      for generating gene disruptions and analyzing the phenotypes are underway to
      ascertain gene function. A future challenge will be to determine interaction and
      regulation of all the genes of an organism. Recent advances in functional genomic
      technology have begun to shine light on such gene network problems at both
      transcriptomic and proteomic levels. Functional genomics will not only elucidate
      what the genes do, but will also help determine when, where and how they are
      expressed as an orchestrated system. In this review, we discuss the functional
      genomics approaches to extract knowledge about transcription regulatory
      mechanisms from combinations of sequence data, microarray data and ChIP data. We
      focus in particular on the budding yeast Saccharomyces cerevisiae.

PMID- 12057688
TI  - Genomics to fluxomics and physiomics - pathway engineering.
AB  - Developments in microanalytical methods are enabling quantitative measurement of
      multiple metabolic fluxes and, in conjunction with transcript and proteomic
      profiling, are revolutionizing the ability of researchers to manipulate
      metabolism through pathway engineering in a variety of species. We review recent
      literature on the advances in genomics, proteomics, fluxomics and computational
      modeling focused on metabolic pathway engineering applications.

PMID- 12057689
TI  - RNA-mediated gene silencing in non-pathogenic and pathogenic fungi.
AB  - Many fungal genomes have now been sequenced and thousands of genes are being
      discovered. Gene disruption or inactivation technology offers an important tool
      not only for elucidating the function of the many unknown genes but also for the
      identification of genes essential for fungal growth and pathogenesis. A variety
      of gene-silencing methods that inhibit genes at the post-transcriptional level
      are now being used in both non-pathogenic and human pathogenic fungi. We focus on
      the recent advances in RNA-mediated gene silencing technologies and their
      potential for functional genomics studies in fungi.

PMID- 12057690
TI  - Genomic analysis using conditional phenotypes generated by antisense RNA.
AB  - Antisense technology has been widely used to regulate gene expression. A
      tetracycline (tet)-regulated antisense-RNA-expressing system has been developed
      and used to downregulate chromosomally derived genes expressed in Staphylococcus
      aureus. This downregulation subsequently provides an evaluation of the virulence
      factor and drug targets. The regulated antisense RNA library allows for genome
      wide analyses of the functions of staphylococcal gene products for growth in
      culture and survival during infection. Moreover, this antisense RNA technology
      may provide a key tool to identify mechanisms of novel antibacterial compound
      action.

PMID- 12057691
TI  - Recent developments in DNA microarrays.
AB  - DNA microarrays are used to quantify tens of thousands of DNA or RNA sequences in
      a single assay. Upon their introduction approximately six years ago, DNA
      microarrays were viewed as a disruptive technology that would fundamentally alter
      the scientific landscape. Supporting this view, the number of applications of DNA
      microarray technology has since expanded exponentially. Here, we review recent
      advances in microarray technology and selected new applications of the
      technology.

PMID- 12057692
TI  - Streptococcus pneumoniae as a genomics platform for broad-spectrum antibiotic
      discovery.
AB  - Streptococcus pneumoniae is a useful tool for the discovery of broad-spectrum
      antibiotics because of its genetic malleability and importance as a pathogen.
      Recent publications of complete chromosomal DNA sequences for S. pneumoniae
      facilitate rapid and effective use of genomics-based technology to identify
      essential genes encoding new targets for antibacterial drugs. These methods
      include computational comparative genomics, gene disruption studies to determine
      essentiality or identify essential genes, and gene expression analysis using
      microarrays and gel-based proteomics. We review how genomics has transformed the
      use of the pneumococcus for the pursuit of new antibiotics, and made it the best
      species for the identification and validation of new antibiotic targets.

PMID- 12057693
TI  - Swan-Ganz catheter assessment of donor hearts: outcome of organs with borderline
      hemodynamics.
AB  - BACKGROUND: High-dosage inotrope use or periods of hypotension may cause
      rejection of donor hearts for transplantation. At our institution, we do not
      refuse potential donor organs based on these criteria alone before Swan-Ganz
      catheter (SGC) assessment. In this study, we evaluate the role of the SGC in
      donor heart resuscitation and selection and assess the outcome of using
      borderline organs. METHODS: We retrospectively analyzed 129 donors assessed
      between 1996 and 1999, all with complete hemodynamic data. Two sets of SGC
      measurements were analyzed: one set from the initial assessments, and one set
      from assessments made just before organ harvesting. The physiologic targets were
      mean blood pressure >60 mm Hg, central venous pressure <12 mm Hg, pulmonary
      capillary wedge pressure <12 mm Hg, left ventricular stroke work index >15 x
      g.m/m(2), and use of only one inotrope. A poorly functioning heart was defined as
      an organ failing on 2 or more of these criteria. Hemodynamic categories were
      defined as A, good function throughout assessment; B, sub-optimal function and
      then improvement; and C, decreasing or poor function throughout. We have a policy
      to avoid allocating sub-optimal organs to high-risk recipients. RESULTS: One
      hundred fourteen donor hearts went on to be transplanted: 75 as orthotopic hearts
      and 39 as heart-lungs (5 of these were heart, lung, and liver transplantations,
      not reported further here). Of the 75 donor hearts used for heart
      transplantations, 53 were from Category A, 9 were from Category B, and 13 were
      from Category C. Of the donor hearts used for the 34 heart-lung transplantations
      16 were from Category A, 10 were from Category B, and 8 were from Category C.
      Three patients died of donor organ failure: 1 of the corresponding hearts was
      from Category B, and 2 were from Category C. When comparing separately the
      outcome of the 2 procedures, we found no significant difference in duration of
      stay in the intensive care unit, requirement for mechanical support, 30-day
      mortality, or 1-year survival among patients with hearts from Categories A, B,
      and C. Ischemic time was the only significant risk factor for death (p = 0.006).
      CONCLUSIONS: Use of organs from Categories B and C permitted expansion of the
      donor pool without compromising short-term outcome. However, these organs should
      be used with caution in combination with other risk factors, in particular long
      ischemic time.

PMID- 12057694
TI  - Use of hearts transplanted from donors with atraumatic intracranial bleeds.
AB  - BACKGROUND: Donor atraumatic intracranial bleed (aICB) is associated with older
      age and may reflect a history of hypertension. Hearts from donors who died of
      aICB may be at increased risk for graft failure because of the associated
      catecholamine surge. We evaluated whether receiving a heart from a donor who had
      an aICB independently affected the outcome of transplantation. METHODS: We
      reviewed adult patients (>18 years) who underwent heart transplantation between
      July 1994 and December 1999. We excluded patients who received non-standard
      hearts (e.g., donor age >55 years). Group 1 received hearts from donors with aICB
      (n = 80), and Group 2 received hearts from donors who did not have aICB (n =
      171). RESULTS: Recipient age, gender, United Network for Organ Sharing status,
      and indication for transplantation were similar for both groups. Donors in Group
      1 were older (41 vs 26 years, p = 0.001), more commonly women (55% vs 20%, p =
      0.001), and more often had history of hypertension (26% vs 2%, p = 0.001).
      Survival to discharge was 86% in Group 1 and 95% in Group 2. Actuarial 5-year
      survival was 72% for Group 1 and 81% for Group 2 (p = 0.52). Regression analysis
      showed that receiving a heart from a donor with aICB was a risk factor for early
      recipient mortality but not for long-term outcome (odds ratio = 3.25, p = 0.02,
      and hazard ratio = 1.16, p = 0.69, respectively). Donor aICB, female gender, and
      abnormal initial echocardiogram (global hypokinesia) were selected as clinically
      relevant independent risk factors for early mortality of the recipient, using a
      fitted multifactor logistic regression model (goodness-of-fit chi-square p value
      = 0.94). Donor age, accident-to-retrieval time interval, and borderline left
      ventricular hypertrophy did not significantly differ. Five-year freedom from
      transplant coronary artery disease in Group 1 was 74% (vs 80% in Group 2, p =
      0.05). CONCLUSIONS: The trend observed in this series suggests that receiving a
      heart from a donor with aICB is a potential independent risk factor for early
      mortality after transplantation independent of age. Caution should be used when
      evaluating such donors, particularly when other risk factors such as female donor
      or depressed ejection fraction are present.

PMID- 12057695
TI  - Genetic variants of the hemostatic system and development of transplant coronary
      artery disease.
AB  - BACKGROUND: The occurrence of coronary artery disease (CAD) after heart
      transplantation may represent an accelerated inflammatory and thrombotic response
      to coronary vascular endothelial cell injury. Several common mutations involving
      hemostasis and cellular adhesion proteins have been associated with genetic
      susceptibility to native coronary heart disease. The clinical setting of heart
      transplantation provides a unique opportunity to examine the relative
      contribution of circulating (i.e., recipient) vs local vascular (i.e., donor)
      hemostatic components to the occurrence of CAD. METHODS: We performed genotyping
      for several common hemostatic polymorphisms among 53 cardiac transplant patients
      and their heart donors. Patients were observed for an average of 43 months, and
      the presence of transplant CAD was determined by coronary angiography. RESULTS:
      The development of transplant CAD did not relate to recipient hemostatic
      genotype, but 2 donor polymorphisms (PAI-1 4G/5G and alpha(2) integrin C807T)
      were important predictors of transplant CAD. The risk ratio (RR) of transplant
      CAD associated with donor PAI-1 4G/4G genotype was 2.6 (95% confidence interval
      [CI] 1.1-6.2) and was modified by recipient cytomegalovirus status,
      hyperlipidemia, diabetes, and recipient factor XIII Val34Leu genotype. The RR of
      transplant CAD associated with donor alpha(2) integrin 807 T/T genotype was 7.4
      (95% CI, 2.5-22.0). CONCLUSIONS: Genetic and metabolic factors contributed by
      both donor and recipient may interact at the level of the coronary vessel wall in
      the development of transplant-associated CAD, and this finding may provide
      additional support for the importance of local thrombotic response to endothelial
      injury in the pathogenesis of this disorder.

PMID- 12057696
TI  - Reversal of diabetes-induced rat graft transplant coronary artery disease by
      metformin.
AB  - BACKGROUND: Induction of diabetes in rat heterotopic heart transplantation models
      leads to an accelerated form of severe transplant coronary artery disease
      (TxCAD). We undertook this study to determine whether treatment of diabetes with
      metformin would favorably affect TxCAD. METHODS: Heterotopic abdominal heart
      transplantation was performed in rat isograft and allograft models. After
      transplantation, diabetes was induced with streptozotocin. Fifty percent of the
      animals received metformin at 500 mg/kg twice daily. We quantitatively assessed
      TxCAD using histologic sections of harvested hearts at 30 and 60 days with
      computer-assisted morphometry. We compared vessels in the first tertile of the
      area distribution with vessels in the last tertile. RESULTS: Fasting glucose
      levels in metformin-treated animals were 161 +/- 45 mg/dl compared with 400 +/-
      120 mg/dl (p < 0.05) in untreated rats. Treatment with metformin led to decreased
      diabetes-induced TxCAD in the larger vessels. This effect was sustained during
      the study course in the isografts but not in the allografts. Treatment with
      metformin did not prevent progression of TxCAD in the smaller vessels at 60 days.
      CONCLUSIONS: Metformin reduced luminal occlusion and severe TxCAD in the larger
      vessels but did not alter the course of TxCAD in the smaller vessels. These
      results may have therapeutic implications for patients.

PMID- 12057697
TI  - Panel-reactive antibody screening practices prior to heart transplantation.
AB  - BACKGROUND: Evaluation of humoral sensitization, commonly determined by the panel
      reactive antibody (PRA) screen, is accepted as an important part of pre
      transplant assessment. A variety of definitions and approaches to sensitization
      have been described in the literature but no analyses of actual practice have
      been reported. METHODS: We sent surveys to 108 adult heart transplant program
      directors and 20 tissue-typing laboratories to obtain information about their
      approaches to PRA and crossmatch determination and management of sensitized
      patients. RESULTS: Among 65 responding directors (60%), 63.1% were cardiologists
      and 36.9% surgeons. The most common threshold to consider PRA as positive is > or
      = 10%. Fifty-five of the respondents consider reactivity with T or B lymphocytes
      to be significant, whereas 34% consider only T-lymphocyte reactivity. Timing of
      PRA determination varies considerably among programs. Conversion to positive PRA
      results in more frequent PRA assessments and often therapy aimed to decrease the
      degree of sensitization. The most commonly utilized approaches are administration
      of immunoglobulin and plasmapheresis. The complement-dependent cytotoxicity (CDC)
      assay is the most commonly used method for PRA determination, but other
      techniques including flow cytometry and enzyme-linked immunosorbent assay (ELISA)
      are also used. Crossmatches are performed utilizing CDC and flow cytometry
      methods. Many laboratories employ more than one technique. CONCLUSIONS: PRA
      screening, crossmatch determinations and management of sensitized patients vary
      considerably from center to center. Uncertainty exists about the importance of
      PRA values, threshold for treatment and clinical implications of sensitization.
      Important questions about the impact of sensitization on outcomes following heart
      transplantation may not be resolved until the measurement and management of
      sensitization becomes more uniform.

PMID- 12057698
TI  - The incidence of end-stage renal failure in 17 years of heart transplantation: a
      single center experience.
AB  - BACKGROUND: Predictions of the incidence of renal failure within a heart
      transplant population are based on the early experiences of cyclosporine (CsA)
      based immunosuppression. We report a single-center experience of end-stage renal
      failure (ESRF) during a 17-year period encompassing current lower dose CsA
      regimens. METHOD: Prospectively collected data were analyzed on all patients who
      underwent first heart transplants between April 1982 and February 1999 (n = 697).
      We further categorized patients by the date of transplantation into a higher and
      lower dosage maintenance CsA group. RESULTS: End-stage renal failure developed in
      44 patients. The median time to dialysis was 87 months after transplantation and
      was independent of the initial CsA regimens used (p = 0.798). In the ESRF group,
      14 underwent hemodialysis, 28 underwent peritoneal dialysis, and 9 underwent
      renal transplantation. One- and 5-year survival rates after dialysis were 82% and
      62% respectively. The incidence of ESRF at our institution was 5.8%. It increased
      with post-operative survival and was independent of the initial CsA regimen used.
      We found no difference in pre-transplant age, sex, diagnosis, immediate post
      operative creatinine, or the development of diabetes between the ESRF group and
      controls. The ESRF group received higher dosages of CsA within the first post
      transplant year, although this did not reach significance (CsA dosage, 5.9
      microg/kg/day vs 5.1 microg/kg/day, respectively p = 0.075). CONCLUSIONS: Lower
      dosage CsA regimes have not altered the incidence of ESRF at our institution,
      suggesting an individual predisposition to nephropathy. Therefore, reduction in
      the future incidence of ESRF may rely on extremely low-dose or calcineurin-free
      immunosuppression regimes.

PMID- 12057700
TI  - Long-term follow-up after total lymphoid irradiation in pediatric heart
      transplant recipients.
AB  - BACKGROUND: Total lymphoid irradiation (TLI) is used to treat recurrent allograft
      rejection. Short-term success and complication rates have been reported in
      pediatric and adult cardiac transplant populations. We report the long-term
      efficacy and safety of TLI in treating intractable rejection in pediatric
      patients. METHODS: Eight pediatric patients were treated with TLI (7 for
      recurrent rejection, 1 for risk of medication non-compliance). Therapy consisted
      of a mid-plane dose of 8 Gy administered with a 6-MeV linear accelerator using an
      anterior-posterior opposed technique. We reviewed outcomes for a total of 40
      patient-years of follow-up. RESULTS: We encountered rejection (>Grade 2 by
      International Society for Heart and Lung Transplantation criteria) in 56.7% +/-
      34.7% of biopsies performed within 90 days before TLI. Rejection rates dropped to
      3.1% +/- 8.8% within the first 90 days (p < 0.005) after therapy and remained low
      at 5.6% +/- 1.3% (p < 0.05) during the first year after completion of TLI. Median
      time from TLI to the first subsequent rejection episode was 305 days (range, 77
      1,920 days). Long-term follow-up (>3 years) of 5 patients demonstrated a
      continuing low incidence of rejection. Non-Hodgkin's lymphoma was diagnosed in 1
      of 8 patients, graft coronary artery disease in 4 of 8 patients, and restrictive
      cardiomyopathy in 1 of 8 patients after TLI. CONCLUSIONS: Total lymphoid
      irradiation is an effective treatment for recurrent rejection and has short- and
      long-term efficacy. Morbid events may include cancer, graft coronary artery
      disease, and restrictive cardiomyopathy.

PMID- 12057699
TI  - Acute and chronic onset of bronchiolitis obliterans syndrome (BOS): are they
      different entities?
AB  - BACKGROUND: Bronchiolitis obliterans syndrome (BOS), defined as an irreversible,
      staged decline in forced expiratory volume in 1 second (FEV(1)), is an
      established marker of obliterative bronchiolitis. Potential causes of BOS include
      sub-clinical chronic rejection and/or exaggerated healing response following
      acute injury. BOS may thus result from two or more distinct processes, both acute
      and chronic. METHODS: A total of 5,916 measurements of FEV(1) from 204 lung
      transplant recipients surviving at least 6 months after transplantation were
      analyzed. Follow-up ranged from 6 months to 13 years. By adjusting for the acute
      effects of rejection, pulmonary infection and measurement variation on FEV(1)
      trace, patients either had a linear decline characterized by a single acute drop
      in FEV(1) of >15% at BOS onset, or a chronic linear decline in FEV(1). The
      fraction having acute onset was estimated. Acute events occurring within the
      first 6 months were assessed as risk factors for acute onset BOS. RESULTS: Of the
      204 patients, 8% died before BOS onset and 18% were BOS-free at analysis. For 18%
      of patients, BOS onset followed a chronic linear decline in FEV(1) of 3.7% per
      year, with a median time of BOS onset >99 months. For 56% of patients, BOS onset
      followed an acute drop in FEV(1) of median 33.8% (95% CI 19.1% to 39.7%), with
      median onset time of 52 months. During the first 6 months, acute rejection was
      significantly and independently associated with acute onset of BOS (relative risk
      = 1.15 per episode, 95% CI [1.03 to 1.29], p = 0.01), whereas pulmonary infection
      and cytomegalovirus (CMV) infection were not. Acute BOS onset followed a
      documented acute event in the previous 6 months in 38 of 114 (33%) of cases.
      CONCLUSIONS: BOS likely reflects more than one process. Compared with those who
      had a slow linear decline in lung function, acute BOS onset was associated with
      acute rejection in the first 6 months, was often triggered by an acute event and
      had poor prognosis, with obliterative bronchiolitis (OB) the main cause of death.

PMID- 12057701
TI  - Giant cell myocarditis: clinical presentation, bridge to transplantation with
      mechanical circulatory support, and long-term outcome.
AB  - BACKGROUND: The multicenter Giant Cell Myocarditis Registry recorded 64 cases
      from 36 centers before 1996. The median transplant-free survival of 30 patients
      without immunosuppression was 3 months. Of 34 patients who received heart
      transplantations, 9 experienced recurrence of giant cell myocarditis in their
      transplanted hearts and 1 patient died. METHODS: We reviewed our experience in
      340 heart transplantations since 1984. Unexpected giant cell myocarditis was
      found in the explanted hearts of 7 patients (6 men and 1 female, aged 18-65
      years). RESULTS: The duration from the onset of symptoms to assist-device implant
      or transplantation ranged from 11 days to 9 years, whereas the time interval from
      referral or deterioration ranged from 2 days to 4 months. Four patients required
      mechanical circulatory support before surgery (total artificial hearts in 2 and
      left ventricular assist devices in 2), and 3 patients required inotropic drugs.
      Six patients are alive with no sign of recurrent giant cell myocarditis at 12 to
      113 months after surgery. One patient died suddenly 75 months after surgery, and
      autopsy showed severe graft vascular disease with no recurrence of giant cell
      myocarditis. Surveillance, right ventricular endomyocardial biopsy specimens
      showed recurrent asymptomatic giant cell myocarditis in 3 patients at 5 to 13
      months after surgery, and found recurrence in 1 patient 30 months after surgery.
      This patient received augmented immunosuppression. CONCLUSIONS: Giant cell
      myocarditis often is not diagnosed before transplantation. It can present as
      dilated cardiomyopathy with late deterioration, or it can present with rapid
      hemodynamic deterioration. In our experience, these patients can be bridged
      successfully to transplant with mechanical circulatory assist. Giant cell
      myocarditis may recur after transplantation but may respond to augmented
      immunosuppression.

PMID- 12057702
TI  - Myosplint implant and shape-change procedure: intra- and peri-operative safety
      and feasibility.
AB  - BACKGROUND: In patients with dilated cardiomyopathy (DCM), the heart enlarges,
      leading to a corresponding increase in ventricular wall stress. To reduce the
      stress, transventricular tension members (Myosplint, Myocor, Inc.) were implanted
      to change the left ventricle (LV) effective radius and to reduce the LV wall
      stress by 20%. We conducted this study to evaluate the intra- and peri-operative
      safety and feasibility of LV-shape change therapy. METHODS: In 7 patients, all
      diagnosed with DCM, Myosplints were implanted. New York Heart Association class
      ranged from III-IV, and LV end-diastolic diameter ranged from 70 to 102 mm.
      Mitral valve regurgitation was classified as mild in 3 and moderate in 4 cases.
      Four patients underwent mitral valve annuloplasty. RESULTS: We observed no
      significant device-related complications, such as thromboembolism, bleeding,
      device instability, or vascular damage, at 90 days. Early indications in a small
      patient population demonstrate some improvements in clinical parameters.
      CONCLUSIONS: From this initial experience, one may conclude that placement of the
      Myosplint devices can be safely performed without early, significant adverse
      events. In patients with significant mitral valve incompetence, concomitant
      mitral valve repair is indicated to realize the full benefit of the procedure.
      This study also suggests that Myosplints can be safely implanted in combination
      with mitral valve repair. The long-term effect of each procedure on cardiac
      function and survival will require further evaluation.

PMID- 12057703
TI  - Controlled perfusion decreases reperfusion injury after high-flow reperfusion.
AB  - INTRODUCTION: Some investigators have suggested that high pulmonary artery flow
      rates increase the risk of severe reperfusion injury after lung transplantation.
      We hypothesized that controlling the initial flow rate and pulmonary artery
      pressure would decrease the severity of lung dysfunction in the setting of high
      flow reperfusion. METHODS: Using our isolated, ventilated, blood-perfused rabbit
      lung model, all groups underwent lung harvest, 4-hour storage (4 degrees C), and
      blood reperfusion. We measured pulmonary artery pressure, peak inspiratory
      pressure, arterial oxygenation, and wet-to-dry weight ratio. Group 1 (control, n
      = 8) underwent reperfusion at 60 ml/min for 30 minutes. Group 2 (high flow, n =
      8) underwent reperfusion at 120 ml/min for 30 minutes. Group 3 (controlled flow,
      n = 8) underwent initial reperfusion at 60 ml/min for 5 minutes, followed by
      reperfusion at 120 ml/min for 25 minutes. RESULTS: Group 1 had significantly
      improved pulmonary artery pressure, peak inspiratory pressure, arterial
      oxygenation, and wet-to-dry weight ratio measurements compared with groups 2 and
      3 after 30 minutes of reperfusion. However, Group 3 had improved pulmonary artery
      pressure, peak inspiratory pressure, arterial oxygenation, and wet-to-dry weight
      ratio measurements compared with Group 2. CONCLUSIONS: High-flow reperfusion
      results in severe reperfusion injury after lung transplantation. Controlled
      reperfusion using a low initial flow rate decreases the severity of reperfusion
      injury associated with high-flow rates.

PMID- 12057704
TI  - Combination treatment with FTY720 and CTLA4IgG preserves the respiratory
      epithelium and prevents obliterative disease in a murine airway model.
AB  - BACKGROUND: Mouse heterotopic tracheal transplantation offers a reproducible
      model of obliterative bronchiolitis after lung transplantation. CTLA4IgG inhibits
      signaling of the CD28/B7 pathway and induces antigen-specific T-cell
      unresponsiveness. FTY720 induces T-cell apoptosis and sequestration of
      circulating mature lymphocytes. We previously found that CTLA4IgG could prevent
      the development of obliterative airway disease but could not preserve the
      respiratory epithelium of grafted tracheae. We evaluated whether treatment with
      either FTY720 or CTLA4IgG, or with combination FTY720 and CTLA4IgG could preserve
      the respiratory epithelium and inhibit the development of obliterative airway
      disease. METHODS: Tracheae with main bronchi from C3H/He mice were transplanted
      heterotopically into BALB/C mice and harvested on Day 35. Recipient mice received
      either no treatment or treatment with intraperitoneal FTY720, CTLA4IgG, or the
      combination of the 2. RESULTS: Either FTY720 or CTLA4IgG alone significantly
      inhibited the development of obliterative airway disease. However, normal
      ciliated columnar respiratory epithelial cells were lost in the allografts. In
      contrast, combination therapy preserved the respiratory epithelium of the
      allografted tracheae. FTY720 concentration in the tissue was very high; treatment
      with FTY720 inhibited mixed lymphocyte reactions and augmented T-cell apoptosis.
      CONCLUSION: Combination treatment with FTY720 and CTLA4IgG may prevent
      obliterative airway disease.

PMID- 12057705
TI  - Video-assisted thoracoscopic surgery for primary chylopericardium after
      orthotopic heart transplantation.
AB  - Chylopericardium is a rare complication of cardiac surgical procedures. We
      describe a 41-year-old woman who underwent orthotopic heart transplantation and
      developed chylopericardium early in the post-operative period. Because of
      unsuccessful conservative treatment (pericardiocentesis, pericardial drainage,
      low-fat diet with medium-chain triglycerides, and total parenteral nutrition),
      surgical intervention was indicated and the patient successfully underwent right
      sided thoracoscopic duct ligation and partial pericardiectomy (pericardial
      window).

PMID- 12057706
TI  - Successful cardiac transplantation after 4 cases of DeBakey left ventricular
      assist device failure.
AB  - Left ventricular assist devices (LVADs) are an established surgical therapy for
      patients with end-stage heart failure as a bridge to cardiac transplantation.
      Major disadvantages of these devices are thromboembolic events, bleeding
      complications, infections, and malfunctions. We report on our experiences with
      DeBakey LVAD malfunctions requiring LVAD exchange in 4 patients. All patients
      underwent subsequent cardiac transplantation and are doing well now.

PMID- 12057707
TI  - Bilateral diaphragm paralysis following lung transplantation and cardiac surgery
      in a 17-year-old.
AB  - Bilateral diaphragm paralysis is a rare complication of lung transplantation.
      This report describes the development of chronic respiratory failure due to
      bilateral diaphragm paralysis following bilateral lung transplantation and
      closure of a patent foramen ovale. This patient required prolonged mechanical
      ventilation post-operatively; however, he eventually had adequate recovery of
      diaphragm function to wean from mechanical ventilation.

PMID- 12057708
TI  - Further evidence of cardiomyocyte apoptosis in hyperacute rejection.

PMID- 12057709
TI  - Combined heart and kidney transplantation: are two organs better than one?

PMID- 12057710
TI  - Indications for lung transplant referral: physician attitudes.

PMID- 12057711
TI  - Is increased circulating endothelin associated with increased complication rate
      after heart transplantation?

PMID- 12057712
TI  - Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus.
AB  - OBJECTIVE: To review the definition and prevalence of two insulin resistance (IR)
      associated phenotypes, polycystic ovary syndrome (PCOS) and type 2 diabetes
      mellitus, as well as the risk and nature of their simultaneous presentation.
      DESIGN: Review of published literature. RESULT(S): Insulin resistance affects
      between 10% and 25% of the general population. Two common disorders frequently
      associated with IR are PCOS, affecting 4% to 6% of reproductive-aged women, and
      type 2 diabetes mellitus, which is observed in about 2% to 6% of similarly aged
      women. Overall, about 50% to 70% of women with PCOS and 80% to 100% of patients
      with type 2 diabetes mellitus have variable degrees of IR. Insulin resistance and
      its secondary hyperinsulinemia appear to underlie many of the endocrine features
      of PCOS in a large proportion of such patients. The risk of type 2 diabetes
      mellitus among PCOS patients is 5- to 10-fold higher than normal. In turn, the
      risk of PCOS among reproductive-aged type 2 diabetes mellitus patients appears to
      be similarly increased. CONCLUSION(S): It remains to be determined whether PCOS
      and type 2 diabetes mellitus represent no more than different clinical
      manifestations of the same IR syndrome, with their phenotypic differences due to
      the presence or absence of a coincidental genetic defect at the level of the
      ovary or pancreas, respectively, or representing the result of etiologically
      different subtypes of IR syndromes.

PMID- 12057713
TI  - Quinacrine sterilization: the imperative need for american clinical trials.

PMID- 12057714
TI  - Raloxifene treatment increases plasma levels of beta-endorphin in postmenopausal
      women: a randomized, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the effect of the selective estrogen receptor modulator
      raloxifene hydrochloride (Evista, Eli Lilly and Company, Indianapolis, IN) on
      plasma levels of beta-endorphin, and to determine whether beta-endorphin levels
      and menopausal symptoms are related. DESIGN: A randomized, double-blind, placebo
      controlled pilot study. SETTING: Endocrinology outpatient department. PATIENT(S):
      Forty postmenopausal women. INTERVENTION(S): The women received raloxifene, 60
      mg/d, or placebo for 3 months. A questionnaire on climacteric symptoms was
      administered before and after treatment. MAIN OUTCOME MEASURE(S): Circulating
      levels of beta-endorphin, climacteric symptom score, and correlation with beta
      endorphin levels. RESULT(S): Raloxifene treatment significantly increased levels
      of beta-endorphin and did not significantly affect climacteric symptoms, with the
      exception of worsening vasomotor symptoms. No significant relation was seen
      between plasma levels of beta-endorphin and climacteric symptoms. CONCLUSION(S):
      Raloxifene modulates plasma levels of beta-endorphin without concomitantly
      relieving climacteric symptoms, as seen with hormone replacement therapy.

PMID- 12057715
TI  - Effects of the route of estrogen administration and exercise on hormonal levels
      in postmenopausal women.
AB  - OBJECTIVE: To examine the effects of exercise on serum estrogens, growth hormone,
      insulin, cortisol, lactate, and glucose levels in postmenopausal women receiving
      two routes of administration of estrogen replacement therapy (ERT). DESIGN:
      Prospective, randomized, crossover study. SETTING: The general clinical research
      center of an academic medical center. PATIENT(S): Eleven active, postmenopausal
      women. INTERVENTION(S): The patients were screened with exercise stress testing,
      then oral micronized estradiol or transdermal estradiol was administered,
      followed by two 45-minute submaximal exercise tests. Dietary intake before the
      tests was standardized. MAIN OUTCOME MEASURE(S): The study measured maximal heart
      rate and aerobic power (VO2max), and serum levels of estradiol (E2), estrone
      (E1), cortisol, growth hormone (GH), insulin, glucose, and lactate. RESULT(S):
      Growth hormone, cortisol, and insulin all changed significantly in response to
      the 45-minute exercise bouts, but no differences were observed between the oral
      micronized estradiol and transdermal estradiol responses. E2 levels increased
      significantly during the transdermal estradiol 45-minute exercise bout; this
      change did not occur during the oral estradiol exercise bout. In the transdermal
      estradiol treatment group, the E2 levels at +30 and +45 minutes of exercise were
      elevated compared to the post-exercise levels at -15, 0, and 30 minutes. E1 was
      not significantly changed during the 45-minute exercise bouts in either group.
      CONCLUSION(S): During exercise, serum E2 levels rise significantly higher with
      transdermal but not oral routes of E2 administration. However, the elevated
      levels are not prolonged and normalize by 30 minutes after exercise.

PMID- 12057716
TI  - Effect of oral micronized progesterone on androgen levels in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To determine whether the use of oral micronized progesterone (OMP) to
      induce withdrawal bleeding in women suspected of having polycystic ovary syndrome
      (PCOS) alters circulating androgen levels. DESIGN: Prospective clinical trial.
      SETTING: Academic medical center. PATIENT(S): Eight reproductive-aged women with
      PCOS. INTERVENTION(S): Blood was sampled before (week 0) and weekly after (weeks
      1 to 4) the administration of OMP (Prometrium, Solvay Pharmaceuticals, Marietta,
      GA), 100 mg in the morning and 200 mg before bedtime for 7 days. MAIN OUTCOME
      MEASURE(S): The levels of total testosterone (TT), free testosterone (FT), sex
      hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and
      androstenedione (A4) were determined in the blood samples. RESULT(S): In seven of
      the eight women studied, menstrual cycle intervals were >3 months, while one was
      eumenorrheic; six of the eight women had hirsutism (modified Ferriman-Gallwey
      score >7). Mean age was 28.9 +/- 10.4 years and mean body mass index was 33.9 +/-
      4.7 kg/m2. The mean values of TT, FT, SHBG, DHEAS, A4, and 17-OHP did not change
      with OMP administration. However, a higher 17-OHP level was observable at the
      completion of OMP administration (week 2). CONCLUSION(S): We conclude that the
      administration of OMP (100 mg in the morning and 200 mg before bedtime for 7
      days) to induce withdrawal bleeding in women with PCOS does not significantly
      alter circulating androgen or 17-OHP levels, and can be used to time blood
      sampling in these patients.

PMID- 12057717
TI  - N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic
      ovary syndrome.
AB  - OBJECTIVE: To evaluate the effect of N-acetyl-cysteine (NAC) on insulin secretion
      and peripheral insulin resistance in subjects with polycystic ovary syndrome
      (PCOS). DESIGN: Prospective data analysis. SETTING: Volunteer women in an
      academic research environment. PATIENT(S): Six lean and 31 obese subjects, aged
      19-33 years. INTERVENTION(S): Patients were treated for 5-6 weeks with NAC at a
      dose of 1.8 g/day orally. A dose of 3 g/day was arbitrarily chosen for massively
      obese subjects. Six of 31 obese patients with PCOS were treated with placebo and
      served as controls. MAIN OUTCOME MEASURE(S): Before and after the treatment
      period, the hormonal and lipid blood profile and insulin sensitivity, assessed by
      an hyperinsulinemic euglycemic clamp, were evaluated and an oral glucose
      tolerance test (OGTT) was performed. RESULT(S): Fasting glucose, fasting insulin,
      and glucose area under curve (AUC) were unchanged after treatment. Insulin AUC
      after OGTT was significantly reduced, and the peripheral insulin sensitivity
      increased after NAC administration, whereas the hepatic insulin extraction was
      unaffected. The NAC treatment induced a significant fall in T levels and in free
      androgen index values (P<.05). In analyzing patients according to their
      insulinemic response to OGTT, normoinsulinemic subjects and placebo-treated
      patients did not show any modification of the above parameters, whereas a
      significant improvement was observed in hyperinsulinemic subjects. CONCLUSION(S):
      NAC may be a new treatment for the improvement of insulin circulating levels and
      insulin sensitivity in hyperinsulinemic patients with polycystic ovary syndrome.

PMID- 12057718
TI  - The antiandrogenic effect of flutamide improves uterine perfusion in women with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate whether, by blocking androgen action, flutamide can
      decrease and normalize vascular resistance in the uterine artery in patients with
      polycystic ovary syndrome (PCOS). DESIGN: Prospective and controlled study.
      SETTING: Endocrinological Centre of the Department of Obstetrics and Gynecology
      of the University of Cagliari, Italy. PATIENT(S): Twenty-two patients with PCOS
      were enrolled in the study and randomly assigned to one of the following two
      treatments for 3 months: oral administration of flutamide (250 mg twice daily) or
      placebo. INTERVENTION(S): Doppler flow measurement of the uterine artery and
      serum hormone concentration determination during the early follicular phase of
      the menstrual cycle before treatment and during the third month of treatment.
      MAIN OUTCOME MEASURE(S): Pulsatility index (PI) of the uterine artery before and
      during treatment. RESULT(S): The PI of the uterine artery decreased significantly
      during treatment. No difference was found in patients treated with placebo.
      Correlation was found only between the PI values of the uterine artery and DHEAS.
      CONCLUSION(S): The low uterine perfusion that characterizes patients with PCOS
      can be improved by the antiandrogenic effect of flutamide.

PMID- 12057719
TI  - Oral contraceptives suppress cell proliferation and enhance apoptosis of eutopic
      endometrial tissue from patients with endometriosis.
AB  - OBJECTIVE: To evaluate the effects of administering combination oral
      contraceptives (COCs) to patients with endometriosis on the regulation of cell
      growth in the eutopic endometrium. DESIGN: Prospective study. SETTING: Research
      institute and clinical fertility center. PATIENT(S): Thirteen women with
      untreated endometriosis and 13 controls. INTERVENTION(S): Biopsy specimens of the
      eutopic endometrium were obtained from all subjects. Apoptosis, cell
      proliferation, and Bcl-2 and Bax expression were examined at the epithelial and
      stromal levels in the eutopic endometrium from patients with endometriosis before
      and after 30 days of daily exposure to COCs and from controls. MAIN OUTCOME
      MEASURE(S): Apoptotic cells were detected by using the dUTP nick-end labeling
      assay; Ki-67, Bcl-2, and Bax expressions were assessed by using
      immunohistochemical techniques. RESULT(S): After exposure to COCs, apoptosis was
      significantly increased in the eutopic endometrium compared with before COC
      administration, both at epithelial and stromal levels. Cell proliferation was
      significantly lowered by COCs. CONCLUSION(S): COCs showed a positive effect on
      patients with endometriosis by down-regulating cell proliferation and enhancing
      apoptosis in the eutopic endometrium.

PMID- 12057720
TI  - Effect of endometriosis on in vitro fertilization.
AB  - OBJECTIVE: To investigate the IVF outcome for patients with endometriosis.
      DESIGN: Meta-analysis. SETTING: Academic research center. PATIENT(S): A MEDLINE
      search and review of the literature were performed. Patients were classified by
      level of endometriosis, and controls were classified according to the indication
      for IVF. INTERVENTION(S): Bivariate analysis and multivariate logistic regression
      was used to estimate overall effect and control for confounding. MAIN OUTCOME
      MEASURE(S): Pregnancy rates, fertilization rate, implantation rates, and numbers
      of oocytes retrieved. RESULT(S): Twenty-two published studies were included in
      the overall analysis. The chance of achieving pregnancy was significantly lower
      for endometriosis patients (odds ratio, 0.56; 95% confidence interval, 0.44-0.70)
      when compared with tubal factor controls. Multivariate analysis also demonstrated
      a decrease in fertilization and implantation rates, and a significant decrease in
      the number of oocytes retrieved for endometriosis patients. Pregnancy rates for
      women with severe endometriosis were significantly lower than for women with mild
      disease (odds ratio, 0.60; 95% confidence interval, 0.42-0.87). CONCLUSION(S):
      Patients with endometriosis-associated infertility undergoing IVF respond with
      significantly decreased levels of all markers of reproductive process, resulting
      in a pregnancy rate that is almost one half that of women with other indications
      for IVF. These data suggest that the effect of endometriosis is not exclusively
      on the receptivity of the endometrium but also on the development of the oocyte
      and embryo.

PMID- 12057721
TI  - Characteristics of uterine contractility during menses in women with mild to
      moderate endometriosis.
AB  - OBJECTIVE: To establish the role of uterine contractions in retrograde
      menstruation with subsequent abdominal implantation of endometrial tissue.
      DESIGN: Controlled prospective study. SETTING: University hospital-based study.
      PATIENT(S): Infertile women with (n = 22) and without (n = 22) endometriosis.
      MAIN OUTCOME MEASURE(S): Frequency, amplitude, and basal pressure tone of uterine
      contractions; correlation of contractions with retrograde bleeding and presence
      of viable endometrial cells; and dysmenorrhea before and 3 and 24 months after
      surgery. RESULT(S): Compared with controls, patients with endometriosis had
      uterine contractions with higher frequency (22.73 +/- 5.66 osc/10 min vs. 11.09
      +/- 3.26 osc/10 min), amplitude (20.83 +/- 3.94 mm Hg vs. 6.77 +/- 2.83 mm Hg),
      and basal pressure tone (50.14 +/- 16.30 mm Hg vs. 24.68 +/- 6.14 mm Hg).
      Dysmenorrhea was scored as 4.09 +/- 1.44 in patients with endometriosis and 0.86
      +/- 1.42 in controls. Retrograde bleeding was found in 73% of patients with
      endometriosis vs. 9% of controls, and only 45% of patients with endometriosis had
      viable endometrial cells in the cul-de-sac. CONCLUSION(S): Endometriosis may
      result from abnormal myometrial contractility through tubal transportation,
      dissemination, and implantation of endometrial viable cells into the abdomen.

PMID- 12057722
TI  - Reproductive potential of fresh and cryopreserved epididymal and testicular
      spermatozoa in consecutive intracytoplasmic sperm injection cycles in the same
      patients.
AB  - OBJECTIVE: To determine if the cryopreservation of epididymal and testicular
      spermatozoa alters their reproductive potential by examination of patients who
      underwent consecutive cycles of ICSI using fresh and then cryopreserved
      spermatozoa. DESIGN: Retrospective review. SETTING: Tertiary care university
      hospital. PATIENT(S): One hundred sixty-two consecutive cycles of ICSI were
      analyzed. Thirteen patients were identified as having undergone treatment with
      freshly retrieved epididymal spermatozoa; these patients subsequently underwent
      treatment with spermatozoa cryopreserved from that cycle. Eighteen patients
      underwent ICSI with freshly retrieved testicular spermatozoa; these patients
      subsequently underwent treatment with spermatozoa cryopreserved from that cycle.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Fertilization rates and pregnancy
      rates. RESULT(S): The fertilizing capacity of epididymal spermatozoa remained
      unchanged after cryopreservation and subsequent thawing, with fertilization rates
      of 58% and 57% for fresh and cryopreserved spermatozoa, respectively. Testicular
      spermatozoa, however, showed a significant decrease in fertilizing capacity after
      cryopreservation when compared with freshly retrieved spermatozoa (52% and 71%,
      respectively). Pregnancy rates appeared unaffected by the cryopreservation of
      epididymal spermatozoa (fresh, 3/13; frozen, 2/13) or testicular spermatozoa
      (fresh, 2/18; frozen, 5/18). CONCLUSION(S): This study offers further evidence
      that motile epididymal spermatozoa retain their fertilizing capacity after
      cryopreservation. The data presented on testicular spermatozoa suggest that
      although cryopreservation may reduce the fertilizing capacity of testicular
      spermatozoa, there is no decrease in pregnancy rates.

PMID- 12057723
TI  - Prognostic value of the clinical and laboratory evaluation in patients with
      nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy.
AB  - OBJECTIVE: To characterize clinical and laboratory findings in nonmosaic 47,XXY
      patients that may help to predict spermatogenetic activity in their testicles.
      DESIGN: Prospective study. SETTING: Assisted reproductive technology program.
      PATIENT(S): Twenty patients with nonmosaic Klinefelter syndrome who underwent
      testicular sperm retrieval for IVF. MAIN OUTCOME MEASURE(S): The correlation
      between basal FSH, LH and testosterone levels, mean testicular volume, and
      results of the hCG test and presence or absence of sperm after testicular sperm
      extraction (TESE). RESULT(S): Sperm was found in nine patients (45%). The mean
      testicular volume was 7.8 +/- 2.5 mL in men with sperm after TESE and 5.6 +/- 1.2
      mL in those without sperm after TESE; corresponding testosterone levels were 3.5
      +/- 1.2 ng/mL and 1.7 +/- 0.8 ng/mL. Serum levels of FSH and LH did not
      significantly differ between groups. After the hCG test, the mean serum
      testosterone level was 16.0 +/- 6.3 ng/mL in men with sperm after TESE and 6.7 +/
      5.6 ng/mL in those without sperm. CONCLUSION(S): Testicular volume, testosterone
      levels, and results of the hCG test are important predictive factors of
      spermatogenesis in patients with nonmosaic Klinefelter syndrome.

PMID- 12057724
TI  - The clinical therapeutic window for luteinizing hormone in controlled ovarian
      stimulation.
AB  - OBJECTIVE: To discuss the clinical therapeutic window for LH during the
      follicular phase. DESIGN: Review of selected papers that were retrieved through a
      Medline search and a review of clinical trials, the results of which are in the
      process of publication. PATIENT(S): Women undergoing infertility treatment.
      INTERVENTION(S): Recombinant human LH (r-hLH) was administered SC as a supplement
      to FSH during controlled ovarian hyperstimulation. MAIN OUTCOME MEASURE(S):
      Follicular development, E2 production, and endometrial thickness. RESULT(S):
      Optimal follicular maturation is the result of both FSH and LH stimulation. In
      patients with hypogonadotropic hypogonadism, 75 IU of r-hLH and 150 IU of FSH per
      day resulted in more follicles and provided sufficient E2 for optimal endometrial
      proliferation. Additional r-hLH (>250 IU/day), in patients with either
      hypogonadotropic hypogonadism or polycystic ovary disease, may precipitate a
      series of deleterious physiological actions leading to atresia of developing
      follicles. Adding r-hLH to FSH in women treated with GnRH agonist showed no
      benefits in terms of number of mature oocytes, fertilization, and cleavage.
      However, those who experience profound pituitary desensitization may benefit from
      adding LH to the stimulation protocol. No obvious clinical criteria have been
      established to define this group of patients. CONCLUSION(S): A "threshold" and
      "ceiling" level for LH (therapeutic window) is proposed, below which E2
      production is not adequate and above which LH may be detrimental to follicular
      development.

PMID- 12057725
TI  - Chronology of hemodynamic changes in asymptomatic in vitro fertilization patients
      and relationship with ovarian steroids and cytokines.
AB  - OBJECTIVE: To characterize the chronology of hemodynamic changes in in vitro
      fertilization (IVF) cycles and its relationship with circulating ovarian
      steroids, cytokines, and their mediator nitric oxide. DESIGN: Prospective, cross
      sectional study. SETTING: University teaching hospital. PATIENT(S): Eighty-eight
      IVF patients. INTERVENTION(S): Ovarian stimulation with FSH under pituitary
      suppression. MAIN OUTCOME MEASURE(S): Circulating levels of estradiol,
      progesterone, nitrite/nitrate, interleukin-6, vascular endothelial growth factor,
      tumor necrosis factor alpha, aldosterone, norepinephrine, as well as measurements
      of plasma renin activity and mean arterial pressure. RESULT(S): The maximal
      stimulation of the renin-aldosterone and sympathetic nervous systems was seen 7
      days after hCG administration, although values still remained elevated over
      normal control values on day of hCG + 11. Mean arterial pressure in IVF patients
      remained significantly reduced throughout the luteal phase. Changes in the
      stimulation of the renin-aldosterone system correlated temporally with
      progesterone but not estradiol levels. No significant changes were observed in
      circulating concentrations of cytokines investigated or nitric oxide.
      CONCLUSION(S): The circulatory changes and the homeostatic activation of the
      renin-aldosterone system and sympathetic nervous system that consistently develop
      in patients undergoing controlled ovarian hyperstimulation for IVF is a feature
      associated with the luteinization process. These hemodynamic changes occur in the
      absence of variations in the circulating levels of cytokines potentially involved
      in ovarian hyperstimulation syndrome.

PMID- 12057726
TI  - Eight-hydroxy-2'-deoxyguanosine in granulosa cells is correlated with the quality
      of oocytes and embryos in an in vitro fertilization-embryo transfer program.
AB  - OBJECTIVE: To determine the effects of oxidative stress on the quality of oocytes
      and embryos, 8-hydroxy-2'-deoxyguanosine (8-OHdG) in granulosa cells was
      quantitatively studied during an in vitro fertilization and embryo transfer (IVF
      ET) program. DESIGN: Immunocytochemical staining of 8-OHdG in granulosa cells was
      quantitatively estimated using a charge-coupled device camera and analyzed using
      the National Institute of Health Image (NIH Image) freeware on a computer .
      SETTING: Obstetrics and gynecology department in a university hospital.
      PATIENT(S): Ninety-six infertile couples undergoing IVF-ET treatment and
      intracytoplasmic sperm injection (IVF, n = 72; intracytoplasmic sperm injection,
      n = 24). INTERVENTION(S): Oocytes, granulosa cells, and follicular fluids were
      collected 35-36 hours after the administration of hCG. MAIN OUTCOME MEASURE(S): 8
      OHdG indices were obtained for mural [8-OHdG index (m)] and cumulus [8-OHdG index
      (c)] granulosa cells. RESULT(S): A negative correlation between the fertilization
      rate and both 8-OHdG indices (c and m) was found. The rate of production of good
      embryos also showed a negative correlation with the 8-OHdG index (m) and the 8
      OHdG index (c). Negative correlations between the 8-OHdG index (c) and E2 levels
      in follicular fluid were observed. Endometriosis patients showed a higher 8-OHdG
      index (c) than did patients with other infertility causes, such as tubal, male
      factor, and unknown. CONCLUSION(S): Oxidative stress in granulosa cells lowered
      fertilization rates and subsequently led to a decrease in the quality of embryos.
      The quality of oocytes for endometriosis patients was impaired by the presence of
      8-OHdG. This might be one causative factor in infertility in endometriosis
      patients.

PMID- 12057727
TI  - Accuracy of day 3 criteria for selecting the best embryos.
AB  - OBJECTIVE: To assess the accuracy of day 3 morphologic criteria in identifying
      the best embryos. DESIGN: Prospective observational study. SETTING: University
      IVF program. PATIENT(S): One hundred cycles in women desiring blastocyst transfer
      who had > or =3 eight-cell embryos on day 3. INTERVENTION(S): On day 3, the
      embryologist chose the two embryos that would have been transferred that day. On
      day 5, embryos were examined to determine the best and second-best blastocysts.
      MAIN OUTCOME MEASURE(S): Accuracy of day 3 picks as measured in culture on day 5,
      outcome of nontransferred picks, and cryopreservation rate. RESULT(S): All cycles
      reached the blastocyst stage and 73% had cryopreservation. The mean number of
      blastocysts was 4.8 (3.2 on day 5 and 1.6 on day 6). Neither pick was chosen in
      39% of cycles; one pick was transferred in 38%; and both picks were transferred
      in 23%. Of 116 nontransferred picks, 51 were frozen and 65 arrested, with both
      picks arresting in 9 cycles. The single best blastocyst was chosen from the picks
      in 39% of cycles. CONCLUSION(S): Morphologic criteria for cleavage-stage embryo
      selection may fall short when the transfer is limited to two embryos. Culture to
      blastocyst is warranted in this population to avoid high-order multiples and
      still be able to choose the two embryos with the highest implantation potential.

PMID- 12057728
TI  - Laser-assisted removal of necrotic blastomeres from cryopreserved embryos that
      were partially damaged.
AB  - OBJECTIVE: To examine whether the developmental potential of embryos that were
      partially damaged after freezing and thawing can be improved by removal of
      necrotic blastomeres before embryo transfer. DESIGN: Prospective pilot study and
      observational clinical series. SETTING: Private hospital. PATIENT(S): Two hundred
      thirty-five infertile couples undergoing frozen embryo transfer. INTERVENTION(S):
      Removal of necrotic blastomeres from frozen-thawed human embryos. MAIN OUTCOME
      MEASURE(S): Pregnancy and implantation rates. RESULT(S): Removal of necrotic
      blastomeres from partially damaged frozen-thawed embryos before transfer
      increased rates of pregnancy (45.7% vs. 17.1%), ongoing pregnancy (40.0% vs.
      11.4%) and ongoing implantation (16.2% vs. 4.3%) compared with the control group,
      in which necrotic blastomeres were not removed. A similarly high implantation
      rate (16.7%) was seen a subsequent clinical series in which necrotic blastomeres
      were removed from all partially damaged embryos. CONCLUSION(S): The viability of
      partially damaged frozen-thawed embryos can be improved by removal of necrotic
      blastomeres before embryo transfer.

PMID- 12057729
TI  - Comparison of the efficacy and safety of a highly purified human follicle
      stimulating hormone (Bravelle) and recombinant follitropin-beta for in vitro
      fertilization: a prospective, randomized study.
AB  - OBJECTIVE: To compare the efficacy and safety of Bravelle s.c., Bravelle i.m.,
      and Follistim s.c. in patients undergoing controlled ovarian hyperstimulation for
      IVF-ET. DESIGN: Open-label, randomized, parallel group, multicenter study.
      SETTING: Eleven academic and private fertility clinics with experience in IVF-ET.
      PATIENT(S): Infertile premenopausal women with regular ovulatory menstrual cycles
      undergoing IVF-ET. INTERVENTION(S): Down-regulation with leuprolide acetate
      followed by up to 12 days of Bravelle s.c. (n = 60), Bravelle i.m. (n = 59), or
      Follistim s.c. (n = 58); hCG administration, oocyte retrieval, and ET. MAIN
      OUTCOME MEASURE(S): Mean number of oocytes retrieved; patients with ET, chemical,
      clinical and continuing pregnancies; mean peak serum E2 levels; adverse events
      and injection site pain scores. RESULT(S): There were no significant differences
      among treatment groups in mean number of oocytes retrieved, peak serum E2 levels,
      patients with ET, continuing pregnancies, or live births. There were no
      significant differences among the treatment groups in the number, nature, or
      intensity of adverse events. Patients treated with Bravelle s.c. or Bravelle i.m.
      experienced significantly less injection site pain than patients treated with
      Follistim s.c. CONCLUSION(S): Bravelle s.c. and Bravelle i.m. are comparable in
      efficacy and safety to Follistim s.c. in patients undergoing controlled ovarian
      hyperstimulation for IVF-ET.

PMID- 12057730
TI  - Importance of the biopsy date in autologous endometrial cocultures for patients
      with multiple implantation failures.
AB  - OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture by
      the cycle day of the endometrial biopsy. DESIGN: Retrospective study. SETTING:
      University-based IVF center. PATIENT(S): Two hundred eight patients with multiple
      IVF failures. INTERVENTION(S): Embryos were split and randomly allocated to
      growth on autologous endometrial coculture or conventional media. MAIN OUTCOME
      MEASURE(S): Embryo quality and pregnancy outcome. RESULT(S): The overall clinical
      pregnancy rate was 41.8%. Embryos grown on autologous endometrial coculture were
      of higher quality (more blastomeres and less fragmentation) than embryos grown
      with conventional media. Early luteal biopsies (<5 days after LH surge) for
      autologous endometrial coculture did not demonstrate an improvement in embryo
      quality as compared to the significant improvement demonstrated with later luteal
      endometrial biopsies (> or =5 days after LH surge). The date of the biopsy was
      predictive of pregnancy outcome when using autologous endometrial coculture
      (44.7% [> or =5 days after LH surge] vs. 18.8% [<5 days after LH surge], P=.012).
      CONCLUSION(S): We have demonstrated an improvement in embryo quality when using
      autologous endometrial coculture. The improvement in embryo quality and higher
      pregnancy rates were limited to biopsies > or =5 days after the LH surge. This
      suggests that mid/late luteal phase endometrium contains factors that enhanced
      embryo growth and subsequent implantation.

PMID- 12057731
TI  - DNA microarray analysis of the expression profiles of luteinized granulosa cells
      as a function of ovarian reserve.
AB  - OBJECTIVE: To examine the expression profiles of luteinized granulosa cells
      isolated from women with normal or diminished ovarian reserve undergoing in vitro
      fertilization. DESIGN: Expression profiling by complementary DNA microarray
      analysis. SETTING: Women undergoing in vitro fertilization-embryo transfer in a
      university-based fertility clinic. PATIENT(S): Eighteen women with normal or
      decreased ovarian reserve. INTERVENTION(S): All patients were given gonadotropin
      stimulation in preparation for IVF with granulosa cells isolated at the time of
      follicular aspiration. MAIN OUTCOME MEASURE(S): Expression profiles of luteinized
      granulosa cells isolated from each woman were determined by using DNA microarray
      analysis. RESULT(S): Changes in patterns of gene expression in granulosa cells
      were observed between women with normal and diminished ovarian reserve. These
      genes included several anonymous expressed sequence tags and also expressed
      sequence tags that correspond to known genes. CONCLUSION(S): Expression profiling
      of granulosa cells by DNA microarray may yield signature patterns that reflect
      the status of ovarian reserve and the competence of granulosa cells.

PMID- 12057732
TI  - Uterine restoration by radiation sequelae regression with combined pentoxifylline
      tocopherol: a phase II study.
AB  - OBJECTIVE: To determine whether combined pentoxifylline (PTX) and tocopherol
      (vitamin E) treatment can improve uterine radiation-induced sequelae, resulting
      in an improved embryo implantation rate. DESIGN: Retrospective phase II clinical
      trial. SETTING: Volunteers in an oocyte donation program in a public hospital.
      PATIENT(S): Six women aged 31 +/- 4 years, who were irradiated 25 years
      previously for childhood cancer with 20 to 40 Gy including the pelvic area.
      INTERVENTION(S): Four women had taken hormone replacement therapy for primary
      amenorrhea, and two had retained their natural cycle. Treatment consisted of at
      least 12 months of pentoxifylline at 800 mg/day combined with 1000 IU/day of
      tocopherol. MAIN OUTCOME MEASURE(S): Endometrial thickness, uterine volume, and
      uterine artery blood flow were assessed by ultrasonography before and after
      pentoxifylline-tocopherol treatment, under usual estrogen-progesterone (OP)
      administration. RESULT(S): This treatment was well tolerated. All six patients
      improved significantly in endometrial thickness (6.2 +/- 0.6 vs. 3.2 +/- 1.1 mm),
      myometrial dimensions (44 [+/- 5] x 30 [+/- 3] x 20 [+/- 2] vs. 30 [+/- 7] x 22
      [+/- 3] x 16 [+/- 2] mm), and diastolic uterine artery flow. CONCLUSION(S): In
      young women who want to bear children, the combination of pentoxifylline and
      vitamin E can reduce fibroatrophic uterine lesions after childhood irradiation.

PMID- 12057733
TI  - Differential effect of gonadotropin-releasing hormone analogue treatment on
      estrogen levels and sulfatase activity in uterine leiomyoma and myometrium.
AB  - OBJECTIVE: To investigate the effect of GnRH treatment on estrogen levels and
      sulfatase activity in leiomyoma and myometrium tissue. DESIGN: Retrospective
      analyses of tissue obtained in a prospective randomized clinical study. SETTING:
      Gynecology departments of eight hospitals in the Netherlands. PATIENT(S): Thirty
      two patients scheduled for leiomyoma surgery. INTERVENTION(S): Patients were
      randomized to receive either GnRHa (3.75 mg/4 weeks of triptorelin or 3.6 mg/4
      weeks of goserelin) or no GnRHa for 4 months. At subsequent surgery, leiomyoma
      and myometrium samples were collected. MAIN OUTCOME MEASURE(S): Estrone,
      estradiol, and sulfatase activity levels in leiomyoma and myometrium. RESULT(S):
      In myometrium, levels of estrone, estradiol, and sulfatase activity were
      significantly lower in the treated group (to median values of 46%, 21%, and 61%,
      respectively). In leiomyomas of treated patients, the reduction in median estrone
      level (to 65% of untreated value) was comparable to that in myometrium. The
      reduction in estradiol level in leiomyoma, however, was significantly less than
      in myometrium (median to 58% vs. 21%), and no significantly lower sulfatase
      activity was found. CONCLUSION(S): Estradiol and sulfatase results show that the
      effect of GnRHa treatment on leiomyoma differs from the effect on myometrium,
      suggesting a continuing estrogenic stimulus in leiomyoma tissue despite
      treatment.

PMID- 12057735
TI  - Differences between husbands' and wives' approach to infertility affect marital
      communication and adjustment.
AB  - OBJECTIVE: To test a theoretical model of the effect on marital communication and
      adjustment of men's and women's approach to infertility. DESIGN: A cross
      sectional research design involving interviews, questionnaires, and a marital
      discussion task. SETTING: Volunteers from practices of fertility specialists.
      PATIENT(S): Forty-eight couples currently seeking infertility treatment.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Quality of marital communication
      during a marital discussion task and effect of infertility on the marriage.
      RESULT(S): Having children was more important to wives than husbands; wives were
      more involved in trying to have a baby, wanted to talk with their partner more
      about trying to have a baby, and experienced a greater loss of self-esteem than
      did their husbands. To the extent that husbands saw having children as important,
      were involved in trying to have a baby, or wanted to talk with their wives about
      trying to have a baby, the quality of marital communication when discussing
      infertility was less negative, and in turn, wives perceived a more positive
      effect of infertility on their marriage. CONCLUSION(S): Increases in husbands'
      interest and involvement in fertility treatment may lead to positive changes in
      couple communication about infertility and to a more positive effect of
      infertility on the marriage.

PMID- 12057734
TI  - Temperament and character in couples with fertility disorders: a double-blind,
      controlled study.
AB  - OBJECTIVE: To evaluate the personality features of infertile patients. DESIGN: A
      double-blind, controlled study. SETTING: An outpatient facility for diagnosis and
      care of infertility. PATIENT(S): We assessed 142 infertile couples with obstetric
      gynecologic clinical and instrumental examinations. The couples were divided into
      three groups: organic infertility, functional infertility, and infertility of
      uncertain origin. The third group was excluded. INTERVENTION(S): Organic
      infertility and functional infertility were ascertained with gynecologic and
      andrologic clinical examinations, seminal liquid examination, postcoital testing,
      progesterone assay, hysterosalpingography, biopsy of endometrium, and
      laparoscopy. Personality traits were assessed with the Temperament and Character
      Inventory (TCI). MAIN OUTCOME MEASURE(S): Results of the Temperament and
      Character Inventory. RESULT(S): Infertile women showed lower Cooperativeness than
      control women. Women with functional infertility had lower scores in
      Cooperativeness and Self-Directedness than women with organic infertility. Men
      belonging to the functional infertility group had a lower Novelty Seeking score
      than did those of the organic infertility group. Men and women in the functional
      infertility group showed higher Harm Avoidance than those in the organic
      infertility and control groups. CONCLUSION(S): The results emphasize that the
      study of personality in the diagnostic and therapeutic assessment of infertility
      might provide useful predictive elements for functional infertility.

PMID- 12057737
TI  - Hemodynamic state and the role of angiotensin II in ovarian hyperstimulation
      syndrome in the rabbit.
AB  - OBJECTIVE: To investigate the hemodynamic state in the ovarian hyperstimulation
      syndrome (OHSS) in the rabbit model and to determine the role of angiotensin II
      in the pathophysiology of this syndrome. DESIGN: Experimental study. SETTING:
      Physiology laboratory. ANIMAL(S): Female New Zealand rabbits were studied; 16
      rabbits were stimulated with gonadotropins, and 6 were controls. Six of the
      stimulated rabbits received additional treatment with captopril. MAIN OUTCOME
      MEASURE(S): Cardiac index, blood pressure, and heart rate were recorded.
      RESULT(S): Gonadotropin-stimulated rabbits had significant enlargement of ovaries
      that was not modified by captopril. Ascites was present in 80% of animals in the
      OHSS group; captopril significantly decreased the incidence and volume of
      ascites. The three groups did not differ in blood pressure, heart rate, cardiac
      index, and total peripheral resistance. CONCLUSION(S): In rabbits with OHSS,
      ascites are a primary event. Such animals are normotensive and have normal
      vascular resistance and cardiac index. Angiotensin-converting enzyme inhibition
      decreases the incidence of OHSS in the rabbit model by 30%, suggesting that
      angiotensin II may play a role in the formation of ascites.

PMID- 12057736
TI  - Pharmacokinetics and pharmacodynamics of single-chain recombinant human follicle
      stimulating hormone containing the human chorionic gonadotropin carboxyterminal
      peptide in the rhesus monkey.
AB  - OBJECTIVE: To compare the pharmacokinetics of a long-acting FSH analog containing
      the hCG-beta carboxyterminal peptide (recombinant hFSH-CTP) with native
      recombinant hFSH and describe the pharmacodynamics of recombinant hFSH-CTP after
      SC injection in female rhesus monkeys. DESIGN: Rhesus monkey study. SETTING:
      Academic research environment. ANIMAL(S): Ten female rhesus monkeys.
      INTERVENTION(S): Recombinant hFSH and recombinant hFSH-CTP were administered via
      a single SC or IV dose to rhesus monkeys, and serial phlebotomy was performed (n
      = 2 and n = 4 for SC recombinant hFSH and recombinant hFSH-CTP, respectively; for
      IV dosing, n = 1 in each group). An additional two monkeys were pretreated with
      SC ganirelix and received SC recombinant hFSH-CTP after confirmation of pituitary
      suppression. MAIN OUTCOME MEASURE(S): Plasma disappearance rate of recombinant
      hFSH and recombinant hFSH-CTP and serum estradiol levels. RESULT(S): The
      elimination half-life of recombinant hFSH-CTP was twofold and fourfold longer
      than that for recombinant hFSH after SC and IV dosing, respectively. The
      absorption half-life was approximately threefold longer for recombinant hFSH-CTP
      than for recombinant hFSH after SC administration. Recombinant hFSH-CTP
      stimulates estradiol secretion for 5-7 days after an isolated SC dose.
      CONCLUSION(S): Addition of the hCG-beta carboxyterminal peptide to hFSH-beta
      results in an FSH analog with longer absorption and elimination half-lives
      compared with native hormone. This analog is capable of prolonged ovarian
      stimulation in rhesus monkeys after an isolated SC injection.

PMID- 12057738
TI  - Signal transduction pathways involved in macrophage migration induced by
      peritoneal fluid chemotactic factors in stages I and II endometriosis.
AB  - OBJECTIVE: To explore the role of G-protein coupled signaling pathways in
      activation of macrophage migration in endometriosis stages I and II. DESIGN: Case
      controlled study. SETTING: University hospital. PATIENT(S): Fifteen patients
      undergoing laparoscopy for elective sterilization (n = 5) or for diagnosis of
      endometriosis stages I and II associated with infertility (n = 10).
      INTERVENTION(S): Peritoneal fluid samples were collected during laparoscopy. MAIN
      OUTCOME MEASURE(S): Macrophage migration induced by peritoneal fluid from
      patients with endometriosis stages I and II (PF SI-II) and potential G-protein
      coupled receptors and second messengers involved in macrophage activation.
      RESULT(S): Potential G-protein coupled receptors and second messengers involved
      in macrophage activation were evaluated after incubation of U-937 cells
      differentiated into macrophages with inhibitors of phospholipase A and C,
      adenylate cyclase, and protein kinase A and C. Macrophage chemotactic activity
      induced by PF SI-II was inhibited in the presence of a phospholipase C and A2
      inhibitor (IC50= 30 microM) and after treatment with myristoylated protein kinase
      C peptide inhibitor (50 nM). An increase in inositol phosphate (IP3) was also
      observed in macrophages exposed to PF SI-II. Activation of multiple G-proteins in
      macrophages was examined after exposure of cells to PF SI-II in the presence and
      absence of Bordettela pertussis and cholera toxins. No effect on macrophage
      migration was observed. CONCLUSION(S): Macrophage chemotaxis induced by PF SI-II
      appears to involve activation of pertussis toxin-insensitive G-protein coupled
      receptors in macrophages. Our data suggest that these events lead to subsequent
      activation of phospholipases followed by generation of IP3 and potential
      mobilization of intracellular Ca2+. Subsequent phosphorylation of target proteins
      by protein kinase C may regulate the chemotactic responses. The adenylate cyclase
      pathway does not appear to play a role in this process.

PMID- 12057739
TI  - Phospholipids reduce adhesion formation in the rabbit uterine horn model.
AB  - OBJECTIVE: To access the ability of intraperitoneal phospholipids to reduce
      adhesions in a standardized model for gynecologic operations. DESIGN: A
      randomized, experimental, blinded study using the double uterine horn model.
      SETTING: Academic animal research laboratory. ANIMAL(S): Thirty-three Chinchilla
      rabbits. INTERVENTION(S): Phospholipids or Ringer's lactate were
      intraperitoneally administered after bilateral uterine horn injury. MAIN OUTCOME
      MEASURE(S): After 10 days, adhesions were evaluated concerning area and strength
      as well as scores describing tenacity and degree. RESULT(S): Phospholipids
      (median 102.1 mm2) significantly reduce adhesion areas in comparison to surgical
      controls (median 392.2 mm2) and Ringer group (median 323.8 mm2). Scores
      reflecting severity and degree of adhesions support this finding. CONCLUSION(S):
      These results prove the efficacy of phospholipids in the double uterine horn
      model. Future clinical studies are recommended.

PMID- 12057740
TI  - Rigorous thermal control during intracytoplasmic sperm injection stabilizes the
      meiotic spindle and improves fertilization and pregnancy rates.
AB  - OBJECTIVE: To examine the effects of different thermodynamic control systems on
      the temperature stability of human eggs during in vitro manipulation, with the
      integrity of meiotic spindles imaged using the LC-PolScope (Cambridge Research &
      Instrumentation, Inc., Woburn, MA). DESIGN: We performed intracytoplasmic sperm
      injection (ICSI) and/or imaging of eggs with the temperature regulated by three
      different systems: thermostated coverslip (system 1), thermostated coverslip
      combined with objective heater (system 2), and conventional stage warmer (system
      3). SETTING: Academic in vitro fertilization clinic. PATIENT(S): Oocytes were
      aspirated from stimulated ovaries of patients undergoing oocyte retrieval for
      ICSI. INTERVENTION(S): Measurement of temperature regulation in media surrounding
      eggs during in vitro manipulation and imaging. MAIN OUTCOME MEASURE(S): Rate of
      oocytes with spindles, fertilization rates, and clinical pregnancy rates after
      ICSI. RESULT(S): We imaged spindles in more oocytes with system 2 (81.2%) than
      with system 1 (61.4%). Spindles could not be imaged for system 3 because of
      technical limitations. Fertilization rates were significantly higher when oocytes
      were imaged and used for ICSI with system 2 (78.8%) than with system 1 (56.7%) or
      system 3 (64.0%). Most importantly, a significantly higher clinical pregnancy
      rate was observed when oocytes were manipulated with system 2 (51.7%) than with
      system 1 (25.0%) or system 3 (23.1%). No differences were found in average ages,
      number of previous cycles, number of eggs, or day 3 FSH or E2 levels among
      groups. CONCLUSION(S): Imaging meiotic spindles with the PolScope provides an
      intracellular thermostat during ICSI. Rigorous thermal control during ICSI
      stabilized spindles and increased the fertilization and clinical pregnancy rates
      achieved after ICSI. The presence of birefringent spindles in living human eggs
      served as a monitor for in vitro conditions.

PMID- 12057741
TI  - Heterotopic autotransplantation of the ovary with microvascular anastomosis: a
      novel surgical technique.
AB  - OBJECTIVE: To test the feasibility of transplanting an entire ovary with
      anastomosis of the ovarian vascular pedicle. DESIGN: Long-term survival study.
      SETTING: Biological Resources Unit, Cleveland Clinic Foundation. ANIMAL(S): Five
      adult, nonpregnant ewes. INTERVENTION(S): Laparoscopic bilateral oophorectomy was
      performed. Ovaries were autotransplanted into the abdominal wall, and
      microsurgical vascular anastomosis of the ovarian to the inferior epigastric
      vessels was performed. The transplant was removed and evaluated after 7 +/- 1
      days. MAIN OUTCOME MEASURE(S): Blood flow, serum E2 and FSH levels, and
      histologic characteristics. RESULT(S): At follow-up three transplants were
      viable; they showed no signs of necrosis, and patency of the vascular anastomosis
      was confirmed. Serum E2 levels did not change significantly after transplantation
      in the patent vessel group (155.3 +/- 46.1 vs. 125.7 +/- 44.6 pg/mL) or the
      nonpatent vessel group (99 vs. 158 pg/mL). Serum FSH level in the patent vessel
      group did not change significantly from before to after transplantation (70.6 +/-
      37.2 ng/mL vs. 95.1 +/- 17.7 ng/mL), whereas a large increase in FSH level was
      observed in the nonpatent vessel group (52.3 ng/mL vs. 522 ng/mL). The patent
      vessel group had significantly more follicles after transplantation than did the
      nonpatent vessel group (6 +/- 1 vs. 1 +/- 1). CONCLUSION(S): In conjunction with
      improved protocols for cryopreservation, ovarian autotransplantation with
      vascular anastomosis may be superior to current ovarian tissue banking and
      grafting techniques.

PMID- 12057742
TI  - Human sperm aster formation after intracytoplasmic sperm injection with rabbit
      and bovine eggs.

PMID- 12057743
TI  - Bilateral calcified ovarian fibromas in a patient with Sotos syndrome.
AB  - OBJECTIVE: To present a case of bilateral calcified ovarian fibromas in Sotos
      syndrome (cerebral gigantism). DESIGN: Descriptive case study. SETTING: Mackay
      Memorial Hospital. PATIENT(S): A 26-year-old woman with Sotos syndrome and
      bilateral solid adnexal masses on gynecologic ultrasound. INTERVENTION(S):
      Surgical removal of an 8 x 6 x 6 cm left ovarian fibroma and a 3 x 2 x 2 cm right
      ovarian fibroma. MAIN OUTCOME MEASURE(S): Ultrasound. RESULT(S): Histopathologic
      examination revealed bilateral ovarian fibromas with extensive foci of
      calcification and occasional ossification. CONCLUSION(S): The presence of
      bilateral calcified ovarian fibromas in this patient with Sotos syndrome may
      reflect the effects of overgrowth in Sotos syndrome on ovarian tumorigenesis or
      may be a coincidence.

PMID- 12057744
TI  - Spontaneous pregnancy in a patient who was homozygous for the Q106R mutation in
      the gonadotropin-releasing hormone receptor gene.
AB  - OBJECTIVE: To report the occurrence of a spontaneous pregnancy in a patient who
      was homozygous for the Q106R mutation in the GnRH receptor (GnRHR) gene. DESIGN:
      Case report. SETTING: Reproductive endocrinology unit of an academic medical
      center. PATIENT(S): A 27-year-old woman who initially presented with partial
      idiopathic hypogonadotropic hypogonadism and who achieved a spontaneous pregnancy
      3 months after oral contraceptive pill (OCP) withdrawal. INTERVENTION(S): Blood
      sampling for hormonal and genetic investigations, transvaginal ultrasound. MAIN
      OUTCOME MEASURE(S): LH, FSH, E2, and betahCG serum levels. Ultrasound examination
      of the uterine cavity. RESULT(S): Three months after OCP withdrawal, the patient
      was amenorrheic. However, the betahCG serum level was 149 IU/L. Transvaginal
      ultrasound 2 weeks later revealed the presence of one intrauterine sac containing
      two embryos with cardiac activity. At 9 weeks of gestation, no cardiac activity
      was found. A curettage was then performed, and the pathological examination
      indicated the presence of chorionic villi. CONCLUSION(S): OCP withdrawal might
      have induced a transient situation with optimal endogenous pulsatile GnRH
      secretion, thus overriding the GnRH resistance induced by the partially
      inactivating Q106R GnRHR gene mutation and allowing ovulation to occur.

PMID- 12057746
TI  - Implantation and pregnancy rates are higher for oocyte donor cycles after
      blastocyst-stage embryo transfer.

PMID- 12057745
TI  - Successful pregnancy after transient ovarian failure following treatment of
      symptomatic leiomyomata.
AB  - OBJECTIVE: To report a case of transient ovarian failure after treatment of
      symptomatic leiomyomata and review other iatrogenic causes of transient ovarian
      failure. DESIGN: Case report and literature review. SETTING: University
      affiliated private practice. PATIENT(S): A 35-year-old woman with symptomatic
      leiomyomata. INTERVENTION(S): Bilateral uterine artery embolization with
      subsequent abdominal myomectomy to treat unchanged regular heavy menstrual flow.
      MAIN OUTCOME MEASURE(S): Ovarian function. RESULT(S): Because medical therapy
      failed to control her menorrhagia, the patient proceeded with uterine artery
      embolization. She had persistent menorrhagia after bilateral uterine artery
      embolization and underwent exploratory laparotomy and myomectomy. After surgery,
      she had amenorrhea, hot flushes, and elevated FSH levels for 3 months. Ovarian
      function recovered after a short course of oral contraceptives, and the patient
      conceived without assistance. CONCLUSION(S): Several interventions can affect
      normal ovarian function and can lead to permanent or transient ovarian failure.
      Possible causes of transient ovarian failure are radioactive iodine treatment,
      radiation, chemotherapy, pelvic surgery, stress, and uterine artery embolization.
      Before these interventions are applied, the possibility of ovarian failure and
      available preventive measures should be discussed with the patient.

PMID- 12057747
TI  - Natural pregnancy in rabbits that underwent oophorectomy and orthotopic
      allogeneic or autologous ovarian transplantation.

PMID- 12057748
TI  - A prospective randomized study comparing day 3 with blastocyst-stage embryo
      transfer.

PMID- 12057749
TI  - Efficacy of hydroxyethyl starch and haemaccel for the treatment of severe ovarian
      hyperstimulation syndrome.

PMID- 12057750
TI  - Tumor necrosis factor-alpha and interleukin-6 promoter gene polymorphisms are not
      associated with an increased risk of endometriosis.

PMID- 12057751
TI  - Salivary leptin levels during the menstrual cycle and their relation to
      progesterone.

PMID- 12057752
TI  - "Uneasy science"--the pooling of heterogeneous data.

PMID- 12057758
TI  - "Uneasy science"--the pooling of heterogeneous data.

PMID- 12057761
TI  - The iron regulatory proteins: targets and modulators of free radical reactions
      and oxidative damage.
AB  - Iron acquisition is a fundamental requirement for many aspects of life, but
      excess iron may result in formation of free radicals that damage cellular
      constituents. For this reason, the amount of iron within the cell is carefully
      regulated in order to provide an adequate level of a micronutrient while
      preventing its accumulation and toxicity. A major mechanism for the regulation of
      iron homeostasis relies on the post-transcriptional control of ferritin and
      transferrin receptor mRNAs, which are recognized by two cytoplasmic iron
      regulatory proteins (IRP-1 and IRP-2) that modulate their translation and
      stability, respectively. IRP-1 can function as a mRNA binding protein or as an
      aconitase, depending on whether it disassembles or assembles an iron-sulfur
      cluster in response to iron deficiency or abundancy, respectively. IRP-2 is
      structurally and functionally similar to IRP-1, but does not assemble a cluster
      nor exhibits aconitase activity. Here we briefly review the role of IRP in iron
      mediated damage induced by oxygen radicals, nitrogen-centered reactive species,
      and xenobiotics of pharmacological and clinical interest.

PMID- 12057762
TI  - Repair of 8-oxoguanine in Saccharomyces cerevisiae: interplay of DNA repair and
      replication mechanisms.
AB  - 8-Oxo-7,8-dihydroguanine (8-oxoG) is produced abundantly in DNA exposed to free
      radicals and reactive oxygen species. The biological relevance of 8-oxoG has been
      unveiled by the study of two mutator genes in Escherichia coli, fpg, and mutY.
      Both genes code for DNA N-glycosylases that cooperate to prevent the mutagenic
      effects of 8-oxoG in DNA. In Saccharomyces cerevisiae, the OGG1 gene encodes a
      DNA N-glycosylase/AP lyase, which is the functional homologue of the bacterial
      fpg gene product. The inactivation of OGG1 in yeast creates a mutator phenotype
      that is specific for the generation of GC to TA transversions. In yeast,
      nucleotide excision repair (NER) also contributes to the release of 8-oxoG in
      damaged DNA. Furthermore, mismatch repair (MMR) mediated by MSH2/MSH6/MLH1 plays
      a major role in the prevention of the mutagenic effect of 8-oxoG. Indeed, MMR
      acts as the functional homologue of the MutY protein of E. coli, excising the
      adenine incorporated opposite 8-oxoG. Finally, the efficient and accurate
      replication of 8-oxoG by the yeast DNA polymerase eta also prevents 8-oxoG
      induced mutagenesis. The aim of this review is to summarize recent literature
      dealing with the replication and repair of 8-oxoG in Saccharomyces cerevisiae,
      which can be used as a paradigm for DNA repair in eukaryotes.

PMID- 12057763
TI  - Combining structural and bioinformatics methods for the analysis of functionally
      important residues in DNA glycosylases.
AB  - An essential function of DNA glycosylases is the recognition and excision of
      damaged bases in DNA, thereby preserving genomic integrity. Lesion recognition is
      a multistep process, which is only partially revealed by structural analysis of
      the catalytically competent complex. The functional role of additional residues
      can be predicted by combining structural data with analysis of amino acid
      conservation. The following postulate underlies this approach: if a family or
      superfamily can be broken into subgroups with different substrate specificities,
      residues highly conserved between these subgroups represent those important for
      enzyme catalysis and structure maintenance while residues highly conserved within
      a subgroup but not between subgroups represent residues important for substrate
      specificity. We review the bioinformatics approach used for this quantitative
      analysis and describe its application to the Nth superfamily and Fpg family of
      DNA glycosylases. These results serve as a starting point in planning site
      directed mutagenesis experiments to elucidate the functional role of similar and
      dissimilar residues in DNA repair and other proteins.

PMID- 12057764
TI  - The relationship between oxidative/nitrative stress and pathological inclusions
      in Alzheimer's and Parkinson's diseases.
AB  - Alzheimer's (AD) and Parkinson's diseases (PD) are late-onset neurodegenerative
      diseases that have tremendous impact on the lives of affected individuals, their
      families, and society as a whole. Remarkable efforts are being made to elucidate
      the dominant factors that result in the pathogenesis of these disorders.
      Extensive postmortem studies suggest that oxidative/nitrative stresses are
      prominent features of these diseases, and several animal models support this
      notion. Furthermore, it is likely that protein modifications resulting from
      oxidative/nitrative damage contribute to the formation of intracytoplasmic
      inclusions characteristic of each disease. The frequent presentation of both AD
      and PD in individuals and the co-occurrence of inclusions characteristic of AD
      and PD in several other neurodegenerative diseases suggests the involvement of a
      common underlying aberrant process. It can be surmised that oxidative/nitrative
      stress, which is cooperatively influenced by environmental factors, genetic
      predisposition, and senescence, may be a link between these disorders.

PMID- 12057765
TI  - Decreased activity of the antioxidant heme oxygenase enzyme: implications in
      ischemia and in Alzheimer's disease.
AB  - Heme oxygenase (HO) is the rate-limiting enzyme for the degradation of heme, a
      prooxidant, coming from a multitude of heme-containing proteins/enzymes. With the
      action of cytochrome P(450) reductase, HO cleaves the heme ring into biliverdin
      which is converted into bilirubin, both have been shown to have intrinsic radical
      scavenger activities. Iron is also released from the heme core and in its free
      form can act as a catalyst for oxidative stress damage or can be sequested by
      several iron-binding proteins. Under physiological conditions, the newly
      generated iron can be neutralized within the cell. The third product of the
      opening of the porphyrin ring is carbon monoxide, which role has been puzzling.
      It has been reported as a potential neuromodulator, it modulates guanylate
      cyclase activity and has vasodilation, anti-inflammatory and antiapoptotic
      effects. In the brain, HO2 accounts for the vast majority of HO activity. By
      decreasing HO2 activity, one would expect more neuronal damage after oxidative
      stress injury with possible direct implications to acute and chronic
      neurodegenerative disorders. Pharmacological ways to increase neuronal HO
      activity is likely to have therapeutic applications.

PMID- 12057766
TI  - Nontoxic heat shock protein coinducer BRX-220 protects against acute pancreatitis
      in rats.
AB  - BACKGROUND: Nontoxic heat shock protein (HSP) inducer compounds open up promising
      therapeutic possibilities by activating one of the natural and highly conserved
      defense mechanisms of the organism. AIMS: In the present experiments, we examined
      the effects of a HSP coinducer drug-candidate, BRX-220, on the cholecystokinin
      octapeptide (CCK)-induced acute pancreatitis in rats. METHODS: Male Wistar rats
      weighing 240 to 270 g were divided into two groups. In group B, 20 mg/kg BRX-220
      was administered orally, followed by 75 microg/kg CCK subcutaneously three times,
      after 1, 3, and 5 h. This whole procedure was repeated for 5 d. The animals in
      group slashed circleB received physiological saline orally instead of BRX-220,
      but otherwise the protocol was the same as in group B. The rats were
      exsanguinated through the abdominal aorta 12 h after the last administration of
      CCK. We determined the serum amylase activity, the plasma trypsinogen activation
      peptide concentration, the pancreatic weight/body weight ratio, the DNA and total
      protein contents of the pancreas, the levels of pancreatic HSP60 and HSP72, the
      activities of pancreatic amylase, lipase, trypsinogen, and free radical scavenger
      enzymes (superoxide dismutase, catalase, and glutathione peroxidase), the degree
      of lipid peroxidation, protein oxidation, and the reduced glutathione level.
      Histopathological investigation of the pancreas was also performed in all cases.
      RESULTS: Repeated CCK treatment resulted in the typical laboratory and
      morphological changes of experimentally induced pancreatitis. The pancreatic
      levels of HSP60 and HSP72 were significantly increased in the animals treated
      with BRX-220. In group B, the pancreatic total protein content and the amylase
      and trypsinogen activities were significantly higher vs. group slashed circleB.
      The plasma trypsinogen activation peptide concentration, and the pancreatic lipid
      peroxidation, protein oxidation, and the activity of Cu/Zn-superoxide dismutase
      were significantly decreased in group B vs. group slashed circleB, whereas the
      glutathione peroxidase activity was increased. The morphological damage in group
      B was significantly lower than that in group slashed circleB. CONCLUSION: The HSP
      coinducer BRX-220, administered for 5 d, has a protective effect against CCK
      induced acute pancreatitis.

PMID- 12057767
TI  - Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and
      carnosic acid in UVA-irradiated human skin fibroblasts.
AB  - The photoprotective potential of the dietary antioxidants vitamin C, vitamin E,
      lycopene, beta-carotene, and the rosemary polyphenol, carnosic acid, was tested
      in human dermal fibroblasts exposed to ultraviolet-A (UVA) light. The carotenoids
      were prepared in special nanoparticle formulations together with vitamin C and/or
      vitamin E. Nanoparticle formulations, in contrast to dimethylsulphoxide,
      stablized lycopene in the cell culture medium and allowed efficient cellular
      uptake. The presence of vitamin E in the formulation further increased the
      stability and cellular uptake of lycopene. UVA irradiation of the human skin
      fibroblasts led to a 10-15-fold rise in metalloproteinase 1 (MMP-1) mRNA. This
      rise was suppressed in the presence of low microM concentrations of vitamin E,
      vitamin C, or carnosic acid but not with beta-carotene or lycopene. Indeed, in
      the presence of 0.5-1.0 microM beta-carotene or lycopene, the UVA-induced MMP-1
      mRNA was further increased by 1.5-2-fold. This increase was totally suppressed
      when vitamin E was included in the nanoparticle formulation. Heme-oxygenase 1 (HO
      1) mRNA expression was strongly induced by UVA irradiation but none of the
      antioxidants inhibited this effect at the concentrations used in this study.
      Indeed, beta-carotene or lycopene (0.5-1.0 microM) led to a further 1.5-fold rise
      in the UVA-induced HO-1 mRNA levels. In conclusion, vitamin C, vitamin E, and
      carnosic acid showed photoprotective potential. Lycopene and beta-carotene did
      not protect on their own but in the presence of vitamin E, their stability in
      culture was improved and the rise in MMP-1 mRNA expression was suppressed,
      suggesting a requirement for antioxidant protection of the carotenoids against
      formation of oxidative derivatives that can influence the cellular and molecular
      responses.

PMID- 12057768
TI  - AP-1 activation through endogenous H(2)O(2) generation by alveolar macrophages.
AB  - Reactive oxygen species released during the respiratory burst are known to
      participate in cell signaling. Here we demonstrate that hydrogen peroxide
      produced by the respiratory burst activates AP-1 binding. Stimulation of the
      macrophage cell line NR8383 with respiratory burst agonists ADP and C5a increased
      AP-1 binding activity. Importantly, this increase in binding was blocked by
      catalase, confirming mediation by endogenous H(2)O(2). Moreover, exogenously
      added H(2)O(2) mimicked the agonists, and also activated AP-1. Antibodies
      revealed that the activated AP-1 complex is composed predominantly of c-Fos/c-Jun
      heterodimers. Treatment of the cells with ADP, C5a and H(2)O(2) (100 microM) all
      increased the phosphorylation of c-Jun. c-Fos protein was increased in cells
      treated with C5a or high dose (200 microM) H(2)O(2), but not in cells treated
      with ADP. The MEK inhibitor, PD98059, partially blocked the C5a-mediated increase
      in AP-1 binding. A novel membrane-permeable peptide inhibitor of JNK, JNKi, also
      inhibited AP-1 activation. Together these data suggest that C5a-mediated AP-1
      activation requires both the activation of the ERK and JNK pathways, whereas
      activation of the JNK pathway is sufficient to increase AP-1 binding with ADP.
      Thus, AP-1 activation joins the list of pathways for which the respiratory burst
      signals downstream events in the macrophage.

PMID- 12057769
TI  - Kinetics of the reactions of nitrogen dioxide with glutathione, cysteine, and
      uric acid at physiological pH.
AB  - Nitrogen dioxide (NO(2)(*)) is a key biological oxidant. It can be derived from
      peroxynitrite via the interaction of nitric oxide with superoxide, from nitrite
      with peroxidases, or from autoxidation of nitric oxide. In this study,
      submicromolar concentrations of NO(2)(*) were generated in < 1 micros using pulse
      radiolysis, and the kinetics of scavenging NO(2)(*) by glutathione, cysteine, or
      uric acid were monitored by spectrophotometry. The formation of the urate radical
      was observed directly, while the production of the oxidizing radical obtained on
      reaction of NO(2)(*) with the thiols (the thiyl radical) was monitored via
      oxidation of 2,2'-azino-bis-(3-ethylthiazoline-6-sulfonic acid). At pH 7.4, rate
      constants for reaction of NO(2)(*) with glutathione, cysteine, and urate were
      estimated as approximately 2 x 10(7), 5 x 10(7), and 2 x 10(7) M(-1) s(-1),
      respectively. The variation of these rate constants with pH indicated that
      thiolate reacted much faster than undissociated thiol. The dissociation of urate
      also accelerated reaction with NO(2)(*) at pH > 8. The thiyl radical from GSH
      reacted with urate with a rate constant of approximately 3 x 10(7) M(-1) s(-1).
      The implications of these values are: (i) the lifetime of NO(2)(*) in cytosol is
      < 10 micros; (ii) thiols are the dominant 'sink' for NO(2)(*) in cells/tissue,
      whereas urate is also a major scavenger in plasma; (iii) the diffusion distance
      of NO(2)(*) is approximately 0.2 microm in the cytoplasm and < 0.8 microm in
      plasma; (iv) urate protects GSH against depletion on oxidative challenge from
      NO(2)(*); and (v) reactions between NO(2)(*) and thiols/urate severely limit the
      likelihood of reaction of NO(2)(*) with NO* to form N(2)O(3) in the cytoplasm.

PMID- 12057770
TI  - Interleukin-6 protects PC12 cells from 4-hydroxynonenal-induced cytotoxicity by
      increasing intracellular glutathione levels.
AB  - Oxidative stress plays an important role in neuronal cell death associated with
      many different neurodegenerative conditions, and it is reported that 4
      hydroxynonenal (HNE), an aldehydic product of membrane lipid peroxidation, is a
      key mediator of neuronal cell death induced by oxidative stress. Previously, we
      have demonstrated that interleukin-6 (IL-6) protects PC12 cells from serum
      deprivation and 6-hydroxydopamine-induced toxicity. Therefore, in the present
      study, we examined the effects of interleukins on HNE toxicity in PC12 cells.
      Exposure of PC12 cells to HNE resulted in a decrease in levels of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, which was
      due to necrotic and apoptotic cell death. Addition of IL-6 24 h before HNE
      treatment provided a concentration-dependent protection against HNE toxicity,
      whereas neither IL-1beta nor IL-2 had any effect. Addition of glutathione (GSH)
      ethyl ester, but not superoxide dismutase or catalase, before HNE treatment to
      the culture medium protected PC12 cells from HNE toxicity. We found that IL-6
      increases intracellular GSH levels and the activity of gamma-glutamylcysteine
      synthetase (gamma-GCS) in PC12 cells. Buthionine sulfoximine (BSO), an inhibitor
      of gamma-GCS, reversed the protective effect of IL-6 against HNE toxicity. These
      results suggest that IL-6 protects PC12 cells from HNE-induced cytotoxicity by
      increasing intracellular levels of GSH.

PMID- 12057771
TI  - Thiourea protects against copper-induced oxidative damage by formation of a redox
      inactive thiourea-copper complex.
AB  - Although thiourea has been used widely to study the role of hydroxyl radicals in
      metal-mediated biological damage, it is not a specific hydroxyl radical scavenger
      and may also exert antioxidant effects unrelated to hydroxyl radical scavenging.
      Thus, we investigated the effects of thiourea on copper-induced oxidative damage
      to bovine serum albumin (1 mg/ml) in three different copper-containing systems:
      Cu(II)/ascorbate, Cu(II)/H(2)O(2), and Cu(II)/H(2)O(2)/ascorbate [Cu(II), 0.1 mM;
      ascorbate, 1 mM; H(2)O(2), 1 mM]. Oxidative damage to albumin was measured as
      protein carbonyl formation. Thiourea (0.1-10 mM) provided marked and dose
      dependent protection against protein oxidation in all three copper-containing
      systems. In contrast, only minor protection was observed with dimethyl sulfoxide
      and mannitol, even at concentrations as high as 100 mM. Strong protection was
      also observed with dimethylthiourea, but not with urea or dimethylurea. Thiourea
      also significantly inhibited copper-catalyzed oxidation of ascorbate, and
      competed effectively with histidine and 1,10-phenanthroline for binding of
      cuprous, but not cupric, copper, as demonstrated by both UV-visible and low
      temperature electron spin resonance measurements. We conclude that the protection
      by thiourea against copper-mediated protein oxidation is not through scavenging
      of hydroxyl radicals, but rather through the chelation of cuprous copper and the
      formation of a redox-inactive thiourea-copper complex.

PMID- 12057773
TI  - Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen
      peroxide production? A minimalist explanation.
AB  - Toxic effects of superoxide dismutase (SOD) overexpression are commonly
      attributed to increased hydrogen peroxide (H(2)O(2)) production. Still, published
      experiments yield contradictory evidence on whether SOD overexpression increases
      or decreases H(2)O(2) production. We analyzed this issue using a minimal
      mathematical model. The most relevant mechanisms of superoxide consumption are
      treated as pseudo first-order processes, and both superoxide production and the
      activity of enzymes other than SOD were considered constant. Even within this
      simple framework, SOD overexpression may increase, hold constant, or decrease
      H(2)O(2) production. At normal SOD levels, the outcome depends on the ratio
      between the rate of processes that consume superoxide without forming H(2)O(2)
      and the rate of processes that consume superoxide with high (>/= 1) H(2)O(2)
      yield. In cells or cellular compartments where this ratio is exceptionally low (<
      1), a modest decrease in H(2)O(2) production upon SOD overexpression is expected.
      Where the ratio is higher than unity, H(2)O(2) production should increase, but at
      most linearly, with SOD activity. The results are consistent with the available
      experimental observations. According to the minimal model, only where most
      superoxide is eliminated through H(2)O(2)-free processes does SOD activity have
      the moderately large influence on H(2)O(2) production observed in some
      experiments.

PMID- 12057772
TI  - Mitochondrial superoxide production during oxalate-mediated oxidative stress in
      renal epithelial cells.
AB  - Crystals of calcium oxalate monohydrate (COM) in the renal tubule form the basis
      of most kidney stones. Tubular dysfunction resulting from COM-cell interactions
      occurs by mechanism(s) that are incompletely understood. We examined the
      production of reactive oxygen intermediates (ROI) by proximal (LLC-PK1) and
      distal (MDCK) tubular epithelial cells after treatment with COM (25-250
      microg/ml) to determine whether ROI, specifically superoxide (O(2)(*-)),
      production was activated, and whether it was sufficient to induce oxidative
      stress. Employing inhibitors of cytosolic and mitochondrial systems, the source
      of ROI production was investigated. In addition, intracellular glutathione (total
      and oxidized), energy status (ATP), and NADH were measured. COM treatment for 1
      24 h increased O(2)(*-) production 3-6-fold as measured by both lucigenin
      chemiluminescence in permeabilized cells and dihydrorhodamine fluorescence in
      intact cells. Using selective inhibitors we found no evidence of cytosolic
      production. The use of mitochondrial probes, substrates, and inhibitors indicated
      that increased O(2)(*-) production originated from mitochondria. Treatment with
      COM decreased glutathione (total and redox state), indicating a sustained
      oxidative insult. An increase in NADH in COM-treated cells suggested this
      cofactor could be responsible for elevating O(2)(*-) generation. In conclusion,
      COM increased mitochondrial O(2)(*-) production by epithelial cells, with a
      subsequent depletion of antioxidant status. These changes may contribute to the
      reported cellular transformations during the development of renal calculi.

PMID- 12057774
TI  - GABA(A) receptor modulation of the rewarding and aversive effects of ethanol.
AB  - Ethanol has been shown to exert many of its biochemical and behavioral effects
      through an interaction with the gamma-aminobutyric acid (GABA) receptor system.
      This review focuses on a subset of studies that has used self-administration, as
      well as place and taste conditioning, procedures to investigate a role for the
      GABA(A) receptor system in modulating the rewarding and aversive effects of
      ethanol. Potential advantages and disadvantages of each procedure are also
      discussed. A significant amount of evidence supports the suggestion that GABA(A)
      receptors are important modulators of the motivational effects of ethanol,
      although most of the findings have been obtained from studies examining oral
      ethanol self-administration. Relatively fewer studies have investigated ethanol
      place and taste conditioning. All self-administration studies reviewed used rats,
      whereas most conditioning studies used mice. Results of these studies show that
      GABA(A) antagonists and inverse agonists reduce ethanol self-administration under
      limited-access conditions. The effect of GABA(A) agonists on ethanol self
      administration is less clear due to their bidirectional effects. GABA(A) receptor
      antagonists have been shown to increase ethanol-induced conditioned place
      preference and conditioned taste aversion in mice and decrease ethanol-induced
      conditioned taste aversion in rats. Issues related to interpretation and
      integration of these findings across models and species are considered. The
      integration of data from self-administration and conditioning procedures is
      necessary to define the role of GABA(A) receptors in modulating the rewarding and
      aversive effects of ethanol and may lead to the development of pharmacotherapies
      that target GABA(A) receptors to treat alcoholism in human beings.

PMID- 12057775
TI  - Alcohol-induced alterations in ERD/ERS during an auditory memory task.
AB  - The purpose of the present study was to examine the effects of alcohol on EEG
      event-related desynchronization (ERD) and event-related synchronization (ERS) of
      the 4-6, 6-8, 8-10, and 10-12 Hz frequency bands during an auditory memory task.
      Twenty subjects performed an auditory memory task during which the EEG was
      recorded. Half the subjects performed the task without the administration of
      alcohol and half under the influence of alcohol ( approximately 0.7 g/l). The
      administration of alcohol itself did not alter the ERD/ERS responses. However,
      when the effects of alcohol were studied as a function of time and task (encoding
      vs. retrieval), we observed significant effects in the 4-6, 6-8, and 8-10 Hz
      frequency bands such that the administration of alcohol decreased the early
      appearing ERS responses during auditory encoding and increased the later
      appearing ERD responses during retrieval. Our results indicate that alcohol has
      disorganizing effects on brain electric oscillatory systems in the theta and
      lower alpha frequency range during cognitive processing.

PMID- 12057776
TI  - Ethanol self-administration in Maudsley reactive and Maudsley nonreactive inbred
      rats.
AB  - This study was performed to investigate ethanol self-administration in inbred
      Maudsley rats, which were selected for differences in stress susceptibility and
      which often differ in their home cage ethanol consumption. Adult, male, Maudsley
      reactive (MR/Har) and Maudsley nonreactive (MNRA/Har) rats were tested in a
      standard protocol for the sucrose-substitution procedure for the initiation of
      self-administration of ethanol in an operant setting. Before and after initiation
      for self-administration in the operant setting, rats were tested for home cage
      consumption of 10% (vol./vol.) ethanol in a two-bottle test for 14 consecutive
      days. During the sucrose-substitution procedure, MNRA/Har rats consumed more
      sucrose and ethanol than did MR/Har rats. In addition, MNRA/Har rats self
      administered a greater amount of ethanol during a concentration manipulation with
      the use of a fixed ratio (FR) 4 response requirement. However, both strains self
      administered low amounts of 10% ethanol (MNRA/Har, 0.15 g/kg/day; MR/Har, 0.08
      g/kg/day) after concentration manipulation compared with those observed in
      outbred rats and alcohol-preferring rats tested under identical conditions in
      other studies. Both MR/Har and MNRA/Har rats markedly increased their ethanol
      intake in the home cage after the initiation protocol, but there was no
      difference between MR/Har and MNRA/Har on that measure. The failure of MR/Har
      rats to self-administer ethanol was inconsistent with their home cage drinking in
      other studies, and this is distinctly different from the self-administration
      pattern of high-alcohol-drinking rat lines tested in this paradigm.

PMID- 12057777
TI  - Uptake of acetaldehyde-modified (ethylated) low-density lipoproteins by mouse
      peritoneal macrophages.
AB  - The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs)
      by murine peritoneal macrophages is described and compared with the uptake of
      acetylated LDLs. The fluorescent marker DiI was used. No competition between
      ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not
      inhibited by polyinosinic acid or fucoidin. Our conclusion is that uptake of
      ethylated and acetylated LDLs can be done by two different receptors.

PMID- 12057778
TI  - Differences in ethanol-induced conditioned taste aversion in Sardinian alcohol
      preferring and Sardinian alcohol-nonpreferring rats.
AB  - In the present study, we investigated whether aversion to the pharmacological
      effects of ethanol developed to a differential extent in selectively bred
      Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats,
      and whether this different response was consistent with their genetically
      determined differences in ethanol preference and consumption. To this purpose, a
      conditioned taste aversion paradigm was used. Male sP and sNP rats were exposed
      to five sessions in which a 20-min availability of a saccharin solution (1 g/l)
      was paired to the injection of ethanol (0, 0.5, or 1 g/kg, i.p.), delivered
      immediately after removal of the saccharin bottle (conditioning phase).
      Subsequently, the choice between saccharin solution and water was offered for 18
      consecutive daily 20-min sessions (postconditioning phase). Ethanol at 1g/kg
      produced a marked aversion to saccharin in sNP rats: The reduction in saccharin
      intake was already evident on the second day of the conditioning phase and lasted
      for 15 days of the postconditioning phase. In contrast, this dose of ethanol
      elicited a modest, if any, conditioned taste aversion in sP rats, although blood
      ethanol levels were comparable to those assessed in sNP rats. These results
      indicate the existence of a differential degree of aversion to the
      postingestional effects of ethanol between sP and sNP rats, and support the
      suggestion that it may contribute, at least in part, to the opposite preference
      for and consumption of ethanol monitored in these rat lines.

PMID- 12057779
TI  - Acute ethanol treatment increases level of progesterone in ovariectomized rats.
AB  - To determine whether an increased level of progesterone in adult female rats
      after acute ethanol treatment, described previously in our study, is the result
      of activation of adrenal glands, we analyzed adrenal cortex morphologically and
      measured serum levels of corticosterone and progesterone in ovariectomized rats.
      In addition, a possible involvement of the opioid system in an observed
      phenomenon was tested. Adult female Wistar rats were ovariectomized, and 3 weeks
      after surgery they were treated intraperitoneally with (a) ethanol (4 g/kg), (b)
      naltrexone (5 mg/kg), followed by ethanol (4 g/kg) 45 min later, and (c)
      naltrexone (5 mg/kg), followed by saline 45 min later. Untreated and saline
      injected rats were used as controls. The animals were killed 0.5 h after ethanol
      administration. Morphometric analysis was carried out on paraffin sections of
      adrenal glands, stained with hematoxylin-eosin, and the following parameters were
      determined: absolute volume of the zona glomerulosa, the zona fasciculata, and
      the zona reticularis; numerical density, volume, and the mean diameter of
      adrenocortical cells and of their nuclei; and mean diameter and length of
      capillaries. The results showed that acute ethanol treatment significantly
      increased absolute volume of the zona fasciculata and length of its capillaries
      but did not alter other stereological parameters. Also, serum levels of
      corticosterone and progesterone were enhanced. Pretreatment with naltrexone had
      no effect on ethanol-induced changes. These findings are consistent with our
      previous hypothesis that an ethanol-induced increase of the progesterone level in
      adult female rats originates from the adrenal cortex.

PMID- 12057780
TI  - Ethanol signals for apoptosis in cultured skin cells.
AB  - Ethanol is commonly used in cosmetic and pharmaceutical preparations. To test
      whether ethanol may cause apoptosis in skin cells, we treated A431 epidermoid
      skin cells and neonatal human primary skin cells with different concentrations of
      ethanol, for different time periods. Ethanol was toxic to cells in both a dose-
      and time-dependent manner and increased the percentage of cells undergoing
      apoptosis. Treatment of cells with 40 and 100 mM ethanol increased release of the
      proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) into culture
      medium and increased its expression in cells. The TNF-alpha was toxic to A431
      epidermoid skin cells at concentrations similar to those released by cells on
      exposure to ethanol. Ethanol-treated cells examined by electron microscopy showed
      organelle damage, condensed chromatin, and apoptotic bodies. Therefore, even at
      low concentrations, ethanol may induce apoptosis in skin cells by enhancing the
      effects of TNF-alpha.

PMID- 12057781
TI  - Biphasic versus triphasic oral contraceptives for contraception.
AB  - Side effects caused by oral contraceptives discourage compliance with and
      continuation of oral contraceptives. A suggested disadvantage of biphasic oral
      contraceptive pills compared to triphasic oral contraceptive pills is an increase
      in breakthrough bleeding. We examined this potential disadvantage by conducting a
      systematic review comparing biphasic oral contraceptives with triphasic oral
      contraceptives in terms of efficacy, cycle control, and discontinuation because
      of side effects. We included randomized, controlled trials comparing any biphasic
      oral contraceptive with any triphasic oral contraceptive when used to prevent
      pregnancy. Only two trials of limited quality met our inclusion criteria.
      Larranaga compared two biphasic and one triphasic pills, each containing
      levonorgestrel and ethinyl estradiol. No important differences emerged, and the
      frequency of discontinuation because of medical problems was similar with all
      three pills. Percival-Smith compared a biphasic pill containing norethindrone
      (Ortho 10/11) with a triphasic pill containing levonorgestrel (Triphasil) and
      another triphasic pill containing norethindrone (Ortho 7/7/7). The biphasic pill
      had inferior cycle control compared with the levonorgestrel triphasic pill. The
      available evidence is limited and of poor quality; the internal validity of these
      trials is questionable. Given that caveat, the biphasic pill containing
      norethindrone was associated with inferior cycle control compared with the
      triphasic pill containing levonorgestrel. This suggests that the choice of
      progestin may be more important that the phasic regimen in determining bleeding
      patterns.

PMID- 12057782
TI  - Therapeutic use of levonorgestrel-releasing intrauterine system in women with
      menorrhagia: a pilot study(1).
AB  - The objective of this study was to evaluate the efficacy and performance, for up
      to 1 year, of an intrauterine system releasing 20 microg/day of levonorgestrel
      (LNG-IUS, Mirena) in the treatment of women with menorrhagia. It was a
      descriptive, prospective, non-comparative study. A 20 microg/day LNG-releasing
      IUS was inserted on any day during bleeding to 44 women (between 24 and 49 years
      of age) who presented with menorrhagia after medical therapies had failed.
      Menstrual patterns were assessed, and hemoglobin concentrations were measured
      before LNG-IUS was inserted and at 3, 6, 9, and 12 months of use. The most common
      bleeding pattern at 3 months after insertion was spotting, and after 6, 9, and 12
      months the majority of women presented with amenorrhea or oligomenorrhea. Three
      women requested removal of the LNG-IUS because of spotting, and six women
      expelled it spontaneously. Hemoglobin levels were improved from 102 g/L to 123
      and 128 g/L at 3 and 12 months, respectively, after insertion of the LNG-IUS (p <
      0.01). At 12 months 79.5% of participants continued the use of LNG-IUS. In
      conclusion, LNG-IUS was an effective treatment for three out of four women with
      menorrhagia and could be an alternative treatment for women with menorrhagia who
      are either contraindicated for or refuse hysterectomy or endometrial ablation.

PMID- 12057783
TI  - Comparative study and evaluation of side effects of low-dose contraceptive pills
      administered by the oral and vaginal route.
AB  - This was a comparative study of side effects and acceptability of low-dose pills
      administered by the oral and vaginal rout. In an experimental clinical trial
      study, undesirable side effects of nausea, dysmenorrhea, breast tenderness,
      gastrointestinal disorders, vertigo, headache, and breakthrough bleeding (BTB)
      were studied. The participants of the case and the control groups were the same
      women. The side effects were compared in 143 women using contraceptive pill
      containing 150 microg levonorgestrel and 30 microg ethinyl estradiol by vaginal
      and oral route. The efficacy and acceptability were evaluated. The side effects
      among the patients who used the contraceptive pills orally were significantly
      higher than among those who used the vaginal route (p < 0.0001). BTB occurred
      more often with the oral route, but there was no significant difference between
      their incidences (p = 0.267). Most participants in this study expressed a high
      level of acceptability with the vaginal route. There was only one unwanted
      pregnancy, which occurred when the participant used the contraceptive pill
      vaginally, but used it incorrectly. Using the contraceptive pill administered by
      vaginal route is a safe method with fewer side effects and more acceptability
      when compared with the oral route.

PMID- 12057784
TI  - Efficacy of a new method of family planning: the Standard Days Method.
AB  - The Standard Days Method is a fertility awareness-based method of family planning
      in which users avoid unprotected intercourse during cycle Days 8 through 19. A
      prospective multi-center efficacy trial was conducted to test, in a heterogeneous
      population, the contraceptive efficacy of the Standard Days Method. A total of
      478 women, age 18-39 years, in Bolivia, Peru, and the Philippines, with self
      reported cycles of 26-32 days, desiring to delay pregnancy at least one year were
      admitted to the study. A single decrement multi-censoring life table analysis of
      the data indicate a cumulative probability of pregnancy of 4.75% over 13 cycles
      of correct use of the method, and a 11.96% probability of pregnancy under typical
      use. This article describes the study and the results. Results suggest that
      despite its requirement that couples modify their sexual behavior when the woman
      is fertile, the Standard Days Method provides significant protection from
      unplanned pregnancy and is acceptable to couples in a wide range of settings.

PMID- 12057785
TI  - Bacteriological cultures of removed intrauterine devices and pelvic inflammatory
      disease.
AB  - Intrauterine devices (IUDs) are highly effective, long-term methods of
      contraception. Although evidence of a direct association between IUD use and
      pelvic inflammatory disease (PID) is scarce, concerns about PID related to IUDs
      use has limited their use throughout the world. We designed this study to examine
      the effect of IUDs on PID. For the study, we recruited 200 participants from
      among women who requested an IUD as a means of contraception. The IUDs were
      removed 36 months later or in case of PID. No PID cases were recorded during the
      follow-up period. Prior to IUD insertion, 121 women (60.5%) had symptoms and/or
      signs of lower genital tract infection, whereas during the follow-up period 179
      women (89.5%) had symptoms and/or signs of lower genital tract infection. The
      Papanicolaou smears were negative for Actinomyces throughout the study period.
      Also, cultures for sexualy transmitted disease microorganisms were negative
      throughout the study period. Following IUD removal, 189 IUD cultures (94.5%) were
      positive. The bacterial flora of the removed IUDs consisted of common aerobic and
      anaerobic microorganisms that do not account for PID. The most common
      microorganisms identified were Staphylococcus coagulase negative, Eschericia
      coli, and Enterococcus faecalis. IUDs are a very effective and safe method of
      contraception if potential recipients are selected carefully. Culture of the
      removed IUDs and therapeutic management of women with positive cultures are not
      recommended when women are asymptomatic for PID.

PMID- 12057786
TI  - Use of MRI to determine the in vivo position of a silicone vaginal barrier
      contraceptive device.
AB  - This study was performed to determine the location of a silicone rubber vaginal
      barrier contraceptive device, the Lea's Shield, in vivo. Two women, one parous
      and one nulligravid, were enrolled in the study. Surface coil, multiplanar
      Magnetic Resonance Imaging (MRI) was performed immediately following insertion of
      the contraceptive device, and was repeated following 35-40 min of normal
      ambulation by the participant.The contraceptive device was markedly hypointense
      to pelvic structures on both T1 and T2 weighted images. Its position within the
      vagina and relationship to the cervix were readily identifiable on MR images. The
      device was located in the upper vagina and completely covered the cervix in both
      patients. The valve appeared closed, and there was no apparent pressure on the
      urethra. The position was not altered by ambulation. In conclusion, MRI was a
      reproducible and rapid means for noninvasively determining the intravaginal
      location and orientation of a barrier contraceptive device. After insertion, the
      Lea's Shield occupies the upper vagina and completely covers the cervix.

PMID- 12057787
TI  - Reasons for using traditional methods and role of nurses in family planning.
AB  - The withdrawal method and other traditional methods of contraception are still
      used in Turkey. Ninety-eight percent of women in Turkey know about modern family
      planning methods and where to find contraceptives. In fact, only one in every
      three women uses an effective method. The aim of this descriptive and
      experimental study was to investigate reasons for using traditional methods and
      the role of nurses in family planning. The women included in the sample were
      visited in their homes by nurses and educated for family planning in four
      sessions. Overall, 53.3% of women were using an effective method. However, 54.3%
      of women living in the Sirintepe district and 41.6% of women living in the
      Yenikent district were still using the traditional methods they used before.
      After the education sessions, the most widely used method was found to be
      intrauterine device (22.8%) in Sirintepe and condom (25%) in Yenikent. There was
      a significant difference in family planning methods between these two districts
      (p < 0.001).

PMID- 12057788
TI  - The influence of vaginal bleeding on the sexual behavior of urban, Hispanic women
      and men.
AB  - Irregular menstrual bleeding associated with use of hormonal contraceptives is a
      leading cause of contraception discontinuation. If bleeding disrupts sexual
      activity, this could contribute to contraceptive discontinuation. The impact of
      bleeding on sexual activities other than intercourse is unknown.A self
      administered questionnaire in Spanish or English was used to collect information
      on demographics and the practice of various sexual behaviors during times of
      vaginal bleeding or spotting. The questionnaire was offered consecutively to 86
      men and 75 women attending urban family-planning and young men's clinics. The men
      and women were approached individually, not as couples. Women reported a mean age
      of 25 years, a wide range of educational attainment, described themselves as
      mostly Hispanic (89%), and most chose the Spanish version of the questionnaire
      (67%). Men also described themselves as mostly Hispanic (80%), and reported a
      similar range of educational attainment, but were younger (mean age of 21, p <
      0.001), and were less likely to choose the Spanish version of the questionnaire
      (23%, p < 0.001).Kissing, breast touching, and receiving non-genital touching did
      not change during bleeding or spotting. Forty-five percent of women reported
      usually receiving genital touching, which declined to 6% during bleeding and to
      10% during spotting (p < 0.001). Similar proportions of women reported usually
      giving genital touching to their partner (50%) during bleeding (41%) or spotting
      (44%). Men also reported usually giving less genital touching to their partner,
      but no change in receiving genital touching during bleeding or spotting. Forty
      percent of women reported usually receiving oral sex, which declined to 4% during
      spotting or to 0% bleeding (p < 0.001). Forty-two percent of women reported
      usually giving oral sex, which declined to 23% during bleeding and to 35% during
      spotting (p = 0.06). Fifty percent of women and 68% of men reported engaging in
      vaginal intercourse. Among women, reported intercourse declined to 7% during
      bleeding and to 26% during spotting (p < 0.001). Among men, reported intercourse
      declined to 19% during bleeding and to 23% during spotting (p < 0.001). The
      presence of vaginal bleeding or spotting is associated with decreases in genital
      sexual behaviors among urban, Hispanic women and men. Such disruptions in sexual
      behavior could contribute to contraceptive discontinuation.

PMID- 12057789
TI  - Factors in contraceptive method choice in Bangladesh: goals, competence,
      evaluation and access.
AB  - In this study, we have extended Bulatao's conceptual framework for selecting the
      determinants of method choice. Attempts have been made to capture Bulatao's
      dimensions directly rather than through proxies. The results of logistic
      regression analysis using the 1996-97 BDHS indicate that as the number of living
      children increases, women prefer non-terminal efficient methods such as the pill
      and injectable/IUD/implant and depend less on inefficient methods such as condom
      and permanent methods such as sterilization. With an increase in marital duration
      and age, women increasingly prefer sterilization as compared with other modern
      methods. The results may indicate a strong preference for male children among
      those in the sample, as women increasingly use permanent methods to prevent
      pregnancy as the number of living male children increases. Condom use increases
      with education of both women and their husbands, compared with other modern
      methods, indicating that more educated couples possibly have the greater
      understanding necessary to use the method. The better educated are significantly
      less likely to use sterilization. The two indicators of contraceptive evaluation,
      side effect and convenience of current modern method, are very important
      considerations in selecting the pill, injectable/IUD/implant, and condom over
      other modern methods. On the basis of convenience, women are most likely to use
      the pill over other modern methods, while they are least likely to use
      sterilization. Condom is the most preferred method on the basis of side effect.
      On the other hand, sterilization is the least preferred of other modern methods
      for the same reason. Sterilization is significantly less common among the
      Muslims, which is likely due to religious reasons, while condom use is
      significantly less common among non-Muslims. The two indicators of contraceptive
      access, accessibility/availability of current modern method and cost of current
      modern method, are very important considerations in pill use, while sterilization
      is less preferred over other modern methods on the basis of both
      accessibility/availability and cost. The programmatic factor visit of family
      planning workers/FWAs significantly increases the likelihood of using the pill
      compared to other modern methods.

PMID- 12057790
TI  - Reference value of semen quality in Chinese young men.
AB  - The purpose of the study was to evaluate semen quality in young Chinese men and
      to establish reference values. Normal healthy young men from seven geographical
      areas were enrolled. The study showed that the mean sperm volume was 2.61 mL, and
      mean percent of sperm with forward progression was 59.89, while median of semen
      viability was 79.0%, and geometric mean of semen density was 55.45 x 10(6)/mL.
      Proportion of routine semen indexes that met World Health Organization (WHO)
      criteria were as follows: 81.9% for semen volume, 91.1% for liquefaction time,
      93.4% for viscosity, 90.8% for pH, 81.3% for sperm with forward progression,
      65.3% for sperm viability, 93.8% for semen density, 98.8% for normal sperm
      morphology, and 89.1% for total sperm count. Participants whose sperm met all WHO
      standard parameters accounted for 42.3%. Because the infertility rate in China is
      about 10-15%, the fifteenth percentile of semen parameters might be used as the
      lower limit of reference values, which may be more appropriate for young Chinese
      men. The fifteenth percentiles of parameters in this study were as follows: 1.5
      mL for semen volume, 7.2 for pH value, 45% for proportion of sperm with forward
      progression, 68% for sperm viability, 30 x 10(6)/mL for semen density, 68% for
      proportion of sperm with normal morphology, and 50 x 10(6) for total sperm count.

PMID- 12057791
TI  - Randomized trial of a Slip-Coat cannula for early abortion.
AB  - The objective of the study was to determine the effectiveness of a 6-mm coated
      cannula with Slip-Coat lubrication to avoid mechanical dilatation for abortion up
      to 712 weeks gestation. A blinded, randomized control trial of 50 healthy women,
      > or =18 years old, up to 54 days pregnant by ultrasound, requesting a surgical
      abortion was conducted. A successful outcome was defined as a completed abortion
      without the need for mechanical cervical dilatation. Of the 50 women, 29 received
      a Slip-Coat cannula, and 21 received a standard cannula. There were no overall
      differences in efficacy of the Slip-Coat cannula (17/29 or 59%) compared with the
      control group (12/21 or 57%, p = 0.91), or the acceptability of the procedure
      (93% versus 91%, respectively, p = 0.74), the level of pain (48 vs. 35,
      respectively, p = 0.052), acceptability of pain (66% vs. 67%, respectively, p =
      0.93), or acceptability of bleeding (90% vs. 86%, respectively, p = 0.67). It was
      concluded that Slip-Coat cannulae were more effective than standard control
      cannulae for women who had no prior live births (6/10 or 60% vs. 0/7 or 0%,
      respectively, p = 0.01). This finding warrants further study.

PMID- 12057792
TI  - Anti-implantation effects of indomethacin and celecoxib in rats.
AB  - Pregnant Wistar rats were used to investigate the anti-implantation effect of
      cyclooxygenase (COX) inhibitors, indomethacin (nonselective COX-1/COX-2
      inhibitor) and celecoxib (specific COX-2 inhibitor). Indomethacin at doses of 2.5
      and 5 mg/kg/day and celecoxib at doses of 40, 80, and 160 mg/kg/day were orally
      administered once daily to each group (n = 8) on Days 3-5 of pregnancy (Day 1 =
      sperm detection). Indomethacin and celecoxib at anti-implantation dosages were
      further investigated for the effects on changes in endometrial vascular
      permeability in pregnant rats and uterine decidualization in pseudopregnant rats.
      The results demonstrated that indomethacin at a dose of 5 mg/kg/day as well as
      celecoxib at doses of 80 and 160 mg/kg/day could significantly reduce the
      proportion of pregnant rats. At the anti-implantation dosages, they exhibited no
      significant effect on proportion of rats with blue dye sites in the endometrial
      vascular permeability study, but they could significantly reduce the uterine
      decidualization. From these findings, the anti-implantation effect of the two COX
      inhibitors may principally be from decidualization defects, and COX inhibitors
      should, therefore, be used with caution in childbearing age women. On the other
      hand, specific COX-2 inhibitors with their good gastric safety profile may have a
      potential role in nonhormonal postcoital contraception.

PMID- 12057793
TI  - Effects of leaf extract of Stephania hernandifolia on testicular gametogenesis
      and androgenesis in albino rats: a dose-dependent response study.
AB  - The present study was undertaken to evaluate the dose-dependent effects of a leaf
      extract of Stephania hernandifolia on testicular activities in albino rats.
      Whether this leaf extract has any toxic effect on metabolic organs or on the
      liver or kidney was studied. Adult male Wistar rats, maintained under standard
      laboratory conditions, were forcefully fed with the aqueous extract of these
      leaves at the dose of 2 g or 4 g of leaves/mL distilled water/100 g body
      weight/day for 28 days. All the animals, along with vehicle-treated controls,
      were killed on the Day 29 of the experiment. Treatment with this leaf extract at
      both doses resulted in significant reduction in relative weight in the testis,
      the seminal vesicles, the prostate, and the epididymis without any significant
      change in the liver and kidney weight in comparison to control. Activities of
      testicular steroidogenic key enzymes and plasma testosterone level were decreased
      significantly, along with a significant reduction in the number of germ cells at
      stage VII of the spermatogenic cycle and in the seminiferous tubular diameter in
      both treated groups in comparison to control. Activities of glutamate
      oxaloacetate transaminase, glutamate pyruvate transaminase, acid phosphatase, and
      alkaline phosphatase were not altered significantly in the liver and kidney in
      both treated groups compared with controls. We concluded that treatment with an
      aqueous extract of leaves resulted in diminution in the activities of testicular
      androgenic key enzymes and plasma level of testosterone along with inhibition of
      spermatogenesis without any induction of hepatic and renal toxicity.

PMID- 12057794
TI  - Autism: a cognitive developmental riddle.
AB  - It has been 60 years since the definitive descriptions of autism, yet it is only
      in the past decade that related advances in cognitive and basic neuroscience have
      begun to be incorporated in clinical practice. Some of the resultant clinical
      advances, which include a trend toward international standardization of diagnosis
      on the basis of behavioral criteria and which, in turn, seem to allow for
      earlier, more secure diagnosis and the application of behavioral therapy in early
      childhood, as well as more thorough genetic studies, are briefly reviewed. The
      three major defects in thought processing that are postulated by cognitive
      neuropsychologists to result in aberrant autistic behaviors are also reviewed and
      linked to recent functional imaging studies in autistic patients and some animal
      and bench research suggestive of both cortical and subcortical developmental
      vulnerabilities in autism. Overall it seems at least possible that
      neuroscientific research may yield results applicable to prevention or
      remediation of autism, a condition heretofore considered irremediable.

PMID- 12057795
TI  - Anterior ischemic optic neuropathy in children: case reports and review of the
      literature.
AB  - Anterior ischemic optic neuropathy, infarction of the optic nerve head owing to
      inadequate perfusion through the posterior ciliary arteries, is a common cause of
      visual loss in adults but is rarely reported in children, in part because the
      diagnosis is overlooked. We report two cases of young children undergoing chronic
      peritoneal dialysis, who suffered bilateral visual loss from anterior ischemic
      optic neuropathy. Predisposing local anatomic and multiple systemic factors
      included a small optic nerve head with little cupping, possible intraocular
      hypertension, and systemic hypotension, hypovolemia, and anemia. The literature
      on anterior ischemic optic neuropathy is reviewed.

PMID- 12057796
TI  - Pediatric migraine equivalents: occurrence and clinical features in practice.
AB  - Migraine equivalents of infancy, childhood, and adolescence are recognized
      periodic, paroxysmal syndromes without associated headache that are thought to be
      migrainous in etiology. Five such equivalents are presently recognized. Their
      clinical features and relative frequency in ambulatory pediatric neurology
      practice have not been well documented. Utilizing a comprehensive, standardized
      computer database, the occurrence of these migraine equivalents in a single
      pediatric neurology practice together with their observed clinical features were
      documented over an 8-year period. Of a total of 5,848 patients in the database,
      of whom 1,106 were migraineurs, 108 patients (1.8% of total, 9.8% of migraineurs)
      were identified to have migraine equivalents. The following distribution among
      migraine equivalents was observed: benign paroxysmal torticollis 11 (10.2% of
      patients with migraine equivalents), benign paroxysmal vertigo 41 (38%),
      abdominal migraine/cyclical vomiting 20 (18.5%), acephalgic migraine 31 (28.7%),
      and acute confusional migraine 5 (4.6%). In each type, with the exception of
      benign paroxysmal torticollis and acute confusional migraine, females clearly
      predominated, and in all types a strong positive family history of migraine was
      elicited (68%-100%). There was variation in the age of onset of a particular
      equivalent with considerable overlap observed. Coexisting more typical migraines
      were observed in from 10% (benign paroxysmal torticollis) to 70% (abdominal
      migraines/cyclical vomiting) of the cases. In conclusion, pediatric migraine
      equivalents occur with relative frequency in ambulatory practice, possessing
      discrete clinical features that have a clear relationship to more typical
      migrainous phenomena.

PMID- 12057797
TI  - Intracranial germ cell tumors: a retrospective study of 44 children.
AB  - This 16-year retrospective study review sought to determine the factors
      influencing prognosis and treatment results of all patients with primary
      intracranial germ cell tumors treated at our hospital who were younger than 17
      years of age at the time of diagnosis. A total of 44 patients were treated during
      the study period, including 32 males and 12 females with a male:female ratio of
      2.67:1. The median age at diagnosis was 12 years and 5 months of age (range = 2
      16 years). The 44 intracranial germ cell tumors consisted of 27 pure germinomas
      (61.4%) and 17 nongerminomatous germ cell tumors, including 10 mixed germ cell
      tumors (22.7%), three yolk sac tumors (7.8%), two immature teratomas (4.5%), and
      two choriocarcinomas (4.5%). Univariate analysis of prognostic factors using
      Kaplan-Meier survival estimates revealed that only histologic tumor type was
      correlated with outcome (P < 0.005). The projected 5-year overall survival and
      event-free survival rate of patients with germinomas vs those with intracranial
      germ cell tumors were 92.6%, 92.6% vs 47.3%, and 42.1%, respectively. Our
      analysis suggests that radiation involving the spinal axis has limited usefulness
      in patients with intracranial germ cell tumor, although better results have been
      obtained for germinomas using radiotherapy in this study.

PMID- 12057798
TI  - Magnetic resonance spectroscopy in childhood brainstem tumors.
AB  - Five children with brainstem tumors and two control patients had magnetic
      resonance spectroscopy studies of the brainstem. Two of the malignant tumor
      patients had magnetic resonance spectroscopy studies before and after radiation
      therapy. The third was irradiated 14 years earlier but developed new symptoms and
      a new brainstem lesion on MRI. Magnetic resonance spectroscopy demonstrated a
      different degree of malignancy between the old and new lesion. The fourth patient
      had magnetic resonance spectroscopy of a chronic, large pontine lesion 6 years
      after diagnosis and radiation. The spectral pattern suggested a low degree of
      malignancy. The fifth patient had neurofibromatosis type 1 with brainstem
      lesions. Magnetic resonance spectroscopy suggested neoplastic tissue of low
      malignancy. These results suggest that magnetic resonance spectroscopy offers
      additional information for anticipating the degree of anaplasia in children with
      brainstem tumors.

PMID- 12057799
TI  - Melatonin production in infants.
AB  - This study investigated the relationships of the excretion of the melatonin
      metabolite, 6-sulfatoxymelatonin, to prenatal, natal, and postnatal variables and
      its possible relation to psychomotor development. nocturnal urinary excretion of
      6-sulfatoxymelatonin was studied over a 13-hour period in 355 term infants at 8
      weeks of age (n = 320) and 16 weeks of age (n = 96). data on a variety of
      perinatal factors including pregnancy course, delivery, early postnatal course,
      birth weight, medical problems, growth (length, weight, and head circumference),
      and psychomotor development were collected at 1, 3, 6, 9, 12, and 18 months. the
      relationship between nocturnal 6-sulfatoxymelatonin excretion at 8 and 16 weeks
      of age and these factors was investigated and analyzed. 6-sulfatoxymelatonin
      levels at 16 weeks of age were significantly lower in infants with abnormal vs
      normal development at 3 months of age (7.27 + 1.44 vs 7.97 + 1.06, p = 0.05) as
      well as at 6 months of age (7.15 + 1.29 vs 7.95 + 1.10, p = 0.04). no other
      significant relation was evident among growth, perinatal complications, medical
      problems, and 6-sulfatoxymelatonin excretion at 8 weeks of age and at 16 weeks of
      age. low melatonin excretion in the first weeks of life correlates with delayed
      psychomotor achievements at 3 and 6 months of age. this association suggests a
      causal or predictive link between melatonin and neurodevelopment in infants.

PMID- 12057800
TI  - Congenital hypotonia with favorable outcome.
AB  - Congenital hypotonia with favorable outcome is characterized by an early neonatal
      onset and a benign clinical course. The old term, proposed by Walton, was benign
      congenital hypotonia, denoting the presence of muscle weakness and hypotonia,
      with the exception of Werdnig-Hoffmann disease. It has been clear that this term
      includes congenital myopathies with definite changes in the muscle fiber.
      However, many cases remain unclarified. The term congenital hypotonia with
      favorable outcome includes only these last cases. A long-term follow-up study of
      children with congenital hypotonia with favorable outcome is presented, and a
      hypothetical mechanism underlying muscle shortening is discussed. The study was
      carried out at the Department of Child Neuropsychiatric Sciences, University "La
      Sapienza" of Rome, during the period 1985-2000, and included 41 patients with
      congenital hypotonia. Our study confirms the good prognosis of congenital
      hypotonia with favorable outcome and suggests a correlation with joint
      hyperlaxity, which is observed in many parents of our children, as if the latter
      developed from the former. On the basis of experimental changes occurring in the
      muscles, we believe that in our cohort the main cause of shortening is caused by
      an increase in joint mobility, which keeps muscles shortened in both the passive
      and active states for a long time. If this view is confirmed by other studies, we
      suggest continuous muscle exercise as a preventive treatment.

PMID- 12057801
TI  - Sturge-Weber syndrome involved frontoparietal region without facial nevus.
AB  - Classic Sturge-Weber syndrome is characterized by a facial nevus and
      hamartomatous lesion in the brain. Hamartomatous lesions are usually located in
      the ipsilateral occipital region of the facial nevus. The other lobes may be
      involved. A few cases of Sturge-Weber syndrome without facial nevus have been
      reported. A 9-month-old male was admitted with the complaint of afebrile seizures
      two times. We observed the third seizure, which was complex partial, in the
      clinic. There was no facial hemangioma. On computed tomography and magnetic
      resonance imaging of the brain we observed findings concordant with the angioma
      in the right frontoparietal region, although the occipital region was intact.
      This patient appears to be the first with Sturge-Weber syndrome without facial
      nevus, and with involvement of the frontoparietal region but not the occipital
      region. We do not know the embryologic basis of this association.

PMID- 12057802
TI  - Empyema of the cavum septum pellucidum.
AB  - The cavum septum pellucidum is not a part of the brain's ventricular system and
      does not communicate with the lateral ventricles. However, under conditions of
      increased intraventricular pressure, cerebrospinal fluid may penetrate the septum
      and cause formation of a cavity. We report a neonate with pus accumulation in the
      cavum septum pellucidum after an episode of ventriculitis. The cavum septum
      pellucidum disappeared after medical and surgical management of the infection and
      increased intracranial pressure.

PMID- 12057803
TI  - Epilepsy surgery in bilateral Sturge-Weber syndrome.
AB  - Two infants with severe drug refractory focal epilepsy caused by Sturge-Weber
      syndrome and extensive cerebral leptomeningeal angiomatosis were referred for
      preoperative video-electroencephalographic evaluation. Brain imaging with
      computed tomography and gadolinium-enhanced magnetic resonance imaging
      demonstrated bilateral disease in both children with a predominance of
      involvement of one hemisphere. Clinical examination and neurophysiology with
      ictal video recording demonstrated epileptogenesis from one hemisphere.
      Successful surgical treatment with functional hemispherectomy was followed by
      good long-term seizure control in both patients. The dramatic seizure control was
      accompanied by markedly improved quality of life for the family and children.
      These cases indicate that the spectrum of children that may benefit from epilepsy
      surgery should not be viewed too restrictively, and subsets of children with
      localization related epilepsy caused by extensive lesions may be resective
      surgical candidates with a good seizure outcome prognosis.

PMID- 12057804
TI  - An unusual presentation of fifth-day fits in the newborn.
AB  - Fifth-day fits are a rare type of seizures in the infant. Tonic-clonic seizures
      have not been reported as a manifestation of this condition. This article
      presents a report of one patient and the value of video-electroencephalogram
      recording in assessing seizures, background electroencephalogram, and treatment.
      We describe a full-term female infant with fifth-day fits presenting with
      generalized tonic-clonic seizures associated with generalized electrical
      discharges, with normal background electroencephalogram activity between
      seizures. The fits rapidly responded to phenobarbital.

PMID- 12057805
TI  - Valproic acid therapy inducing absence status evolving into generalized seizures.
AB  - The authors herein present two children with mild absence epilepsy, having
      intermittent absences, who developed absence status evolving into atonic
      generalized seizures and drop attacks along with progressive disorientation
      induced by relatively small doses of valproic acid. Consciousness and awareness
      were intact before the introduction of valproic acid. Both children, after the
      first dose of valproic acid, developed prolonged and recurrent clusters of
      absences, which became prolonged, with drop attacks occurring in one patient
      associated with progressive disorientation. The electroencephalogram concurrently
      demonstrated prolonged spike-wave discharges, along with disturbance of
      background activity. Discontinuation of valproic acid resulted in immediate
      cessation of the prolonged and repetitive clusters of absence episodes and
      disappearance of drop attacks, along with sensorium clearing. In conclusion,
      although uncommon, a possible induction of absence status and even atonic
      seizures by valproic acid should be taken into account and properly managed by
      abrupt discontinuation of the drug.

PMID- 12057806
TI  - Glutaric aciduria type I diagnosed after poliovirus immunization: magnetic
      resonance findings.
AB  - Glutaric aciduria type I is an uncommon inborn error of metabolism. It is a
      serious disease, often with a fatal outcome. Magnetic resonance imaging findings
      and the clinical course of monozygotic twin females with glutaric aciduria type I
      who were admitted with acute encephalopathic crisis symptoms 3 days after
      immunization for poliovirus are presented in this report. Magnetic resonance
      imaging findings revealed hyperintensity in the putamen, head of the left caudate
      nucleus, and globus pallidus, periventricular white matter (on T(2)-weighted
      images), arachnoid cysts in bilateral temporal regions, and enlargement of the
      sylvian fissures. Glutaric aciduria type I should be included in the differential
      diagnosis of patients with acute encephalopathic crisis occurring shortly after
      poliovirus immunization. Typical magnetic resonance findings guide urinary
      organic acid analysis in these patients.

PMID- 12057807
TI  - Sincipital encephalocele mismanaged as a facial hemangioma.
AB  - A 3-month-old male infant was found to have a protruding mass with irregular
      contour at the root of his nose since birth. The mass protruded more when he
      cried. It was diagnosed and treated as a hemangioma by laser surgery in another
      hospital. However, the lesion recurred 1 week later. Reviewing the previous
      computed tomographic study of the brain, it revealed that the protruding mass
      communicated with the brain. Sincipital encephalocele was diagnosed, and
      craniotomy for excising the encephalocele and repair of the dura were undertaken
      successfully. We report this patient with sincipital encephalocele that was
      misdiagnosed and treated as a vascular malformation on the face. Fortunately,
      there was no complication. The authors stress the importance of accurate
      diagnosis of a lesion near the craniofacial junction to avoid unnecessary surgery
      and possible catastrophes.

PMID- 12057822
TI  - Genetic association analysis of 5-HT(6) receptor gene polymorphism (267C/T) with
      tardive dyskinesia.
AB  - Possible involvement of serotonergic (5-hydroxytryptamine: 5-HT) receptors in the
      pathophysiology of tardive dyskinesia (TD) has been suggested. In the present
      study, the relationship between the 5-HT(6) receptor gene (HTR6) polymorphisms
      and TD was studied in 173 Japanese patients with schizophrenia. The 267C/T allele
      of HTR6 was genotyped using PCR amplification followed by endonuclease digestion.
      The patients with the three 267C/T genotypes showed no significant difference in
      gender, age, duration of illness, or current antipsychotic dose. In addition,
      there were no significant differences in total AIMS scores among patients with
      the three genotypes. Moreover, no significant differences in genotypes and allele
      frequencies were observed between subjects with and without TD. These results
      suggest that the 267C/T polymorphism of HTR6 does not confer increased
      susceptibility to TD.

PMID- 12057824
TI  - Effects of supraphysiological doses of L-thyroxine on cognitive function in
      healthy individuals.
AB  - Cognitive disturbance is commonly associated with disorders of the thyroid gland,
      particularly hypothyroidism, and usually subsides following thyroid hormone
      replacement therapy. In contrast, the effects of thyroid hormones on cognitive
      functions in healthy individuals have rarely been studied. The goal of this open
      label study was to investigate the short-term effects (duration of administration
      45 days on average) of supraphysiological doses of L-thyroxine (L-T(4)) on
      cognitive performance in young, euthyroid, healthy subjects. Eleven subjects
      performed a comprehensive neuropsychological test battery, once without and once
      during administration of supraphysiological doses of L-T(4). There were no
      significant differences in any of the cognitive test results between the two test
      sessions. The results of this study do not support our working hypothesis that
      thyroid hormone can change cognitive performance in young, euthyroid, healthy
      individuals.

PMID- 12057823
TI  - Serotonin transporter polymorphisms and measures of impulsivity, aggression, and
      sensation seeking among African-American cocaine-dependent individuals.
AB  - Considerable evidence indicates that serotonergic mechanisms, particularly the
      serotonin transporter (5HTT), may mediate central effects of cocaine and may also
      be involved in impulsive and aggressive behavior. We investigated whether
      polymorphisms in the 5HTT gene were related to traits of impulsivity, sensation
      seeking, and aggression among cocaine abusers. Standardized measures of these
      personality traits were obtained in a sample of 105 severely affected cocaine
      dependent African-American subjects and 44 African-American controls. Two
      polymorphisms of the 5HTT gene were examined involving the 5' promoter (5HTTLPR)
      region and a 17 base pair variable-number-tandem-repeat (VNTR) marker among
      cocaine patients. No significant relationships were observed between polymorphic
      variants of the 5HTTLPR and VNTR regions and scores on any of the trait measures.
      Similarly, demographic variables and measures of severity of substance use and
      depression were unrelated to allele frequencies or genotype distributions of the
      variants among cocaine patients. As expected, cocaine patients scored
      significantly higher on total scores of impulsivity, aggression, and sensation
      seeking compared to controls. The findings do not seem to support an association
      between these polymorphisms in the 5HTT gene and impulsive-aggressive traits
      among cocaine-dependent African-American individuals.

PMID- 12057825
TI  - Perceptual organization deficits in psychotic patients.
AB  - It has been proposed that a characteristic of schizophrenic processing is an
      abnormality of top-down processing. The relationship between impaired top-down
      processing and symptoms of reality distortion was investigated using a 'degraded
      interference' task. In this task, fragmented stimuli (Stroop words, control words
      and crosses) are presented on a computer screen, and the extent to which they are
      visually integrated is inferred by their interfering properties. It was predicted
      that psychotic individuals would fail to show an interference effect with
      degraded Stroop stimuli. This predicts the absence of a delay in reaction time in
      the experimental condition, which therefore cannot be attributed to a generalized
      deficit. A sample of inpatients experiencing positive symptoms was compared to a
      healthy control group. The results provided support for a deficiency in top-down
      processing, with the psychotic group failing to show the significant degraded
      interference effect found in the healthy controls. Degraded interference was
      associated with low verbal IQ, but with no other symptomatic or demographic
      variables.

PMID- 12057826
TI  - Attentional control and word inhibition in schizophrenia.
AB  - Previous studies have suggested that schizophrenia patients do not utilize
      contextual information efficiently to modulate attentional performance. The goal
      of the current study was to compare the utilization of context in modulating
      responses to irrelevant information on the Stroop task between a group of
      schizophrenia outpatients and matched controls. A single-trial version of the
      Stroop task was used to investigate performance on the Stroop task under three
      expectancy conditions. Eleven schizophrenia outpatients (on and off antipsychotic
      medication) and sixteen matched controls were tested. The schizophrenia patients
      showed: (1) augmented facilitation; (2) interference comparable to normals; and
      (3) normal ability to reduce interference under certain experimental
      circumstances. Schizophrenia patients were able to utilize contextual information
      under certain conditions and could modulate the magnitude of irrelevant word
      interference, although they were not able to overcome the prepotent tendency to
      read the word during the Stroop task as effectively as normals, which was
      reflected in greater Stroop facilitation. This suggests that the integrity or
      impairment of cognitive control functions in schizophrenia is related to the
      complexity of the context representation required to support that function.

PMID- 12057827
TI  - Executive function deficits associated with symptoms of schizotypy and obsessive
      compulsive disorder.
AB  - Research suggests that executive dysfunction is seen both in disorders of the
      schizophrenia constellation and in obsessive-compulsive disorder (OCD), but that
      the patterns of executive deficits may differ. While disorders of the
      schizophrenia spectrum reflect impairment of functions such as integration of
      cognitive activities, a tendency to perseverate, and a failure to notice details
      (e.g. impairment associated with the dorsolateral prefrontal cortex), OCD may
      involve problems of impulse control and regulation of behavior, and an inability
      to maintain cognitive set (e.g. impairment associated with the orbitofrontal
      cortex). The present study examined differences between high-scorers on a measure
      of schizotypy, high-scorers on a measure of OCD, high-scorers on both schizotypy
      and OCD and a control group in performance on executive function tests. As
      expected, the OCD group demonstrated relative deficits on measures thought to
      reflect orbitofrontal functioning. However, contrary to expectations, the
      schizotypal group did not demonstrate deficits on neuropsychological tests
      thought to reflect dorsolateral prefrontal cortex functioning, and the combined
      group showed no executive impairment.

PMID- 12057828
TI  - Response inhibition deficits in obsessive-compulsive disorder.
AB  - Difficulty inhibiting irrelevant information may play a central role in the
      aetiology of obsessive-compulsive disorder (OCD). The aim of the present study
      was to determine whether OCD subjects (n=20) exhibit deficits in behavioural and
      cognitive inhibition compared with a clinical control group diagnosed with panic
      disorder (n=20). All subjects were administered a Go/Nogo task (a measure of
      behavioural inhibition) and a Stroop test (a measure of cognitive inhibition).
      OCD subjects made more commission errors on the Go/Nogo task, and they made more
      errors and displayed longer reaction times on the interference trial of the
      Stroop task. Trends towards correlations were observed between OCD severity
      scores and Stroop reaction time, where the more severe the OCD symptoms the
      faster was the response. No correlations between clinical symptomatology or
      subject demographics and the Go/Nogo task were observed. It was demonstrated that
      OCD subjects exhibit deficits in behavioural and cognitive inhibition, which
      together may underlie the repetitive symptomatic behaviours of the disorder, such
      as compulsions and obsessions.

PMID- 12057829
TI  - The Stereotypy Rating Inventory for frontotemporal lobar degeneration.
AB  - A many behavioral disturbances, Stereotypic behaviors are among the best
      discriminators of Frontotemporal Lobar Degeneration (FTLD). A recent preliminary
      report suggests many of the behavioral symptoms, including stereotypic behaviors
      in FTLD patients, respond to medication with selective serotonin re-uptake
      inhibitors. However, there is no scale that evaluates stereotypic behaviors
      comprehensively. To assess the wide range of stereotypic behaviors encountered in
      FTLD, we developed a new instrument, the Stereotypy Rating Inventory (SRI). The
      SRI assesses five distinctive stereotypic behavioral disturbances often seen in
      patients with FTLD: eating and cooking behaviors, roaming, speaking, movements,
      and daily rhythm. The SRI uses the same technique as the Neuropsychiatric
      Inventory (NPI) in that both the frequency and the severity of each behavior are
      determined. The studies reported here demonstrate the content and concurrent
      validity, as well as inter-rater and test-retest reliability, of the instrument.
      Scores of FTLD patients (n=26) on the SRI were much higher than those of patients
      with Alzheimer's disease (n=46), patients with vascular dementia (n=26), and
      normal control subjects (n=40). The SRI appears to be a useful instrument for
      detecting stereotypic behaviors and monitoring of therapies in FTLD patients.

PMID- 12057830
TI  - Utility scores of symptom profiles in major depression.
AB  - Utility is a measure of undesirability for a specific health state. This study
      determines the utility scores for the individual symptoms of depression, and
      examines the impact that personal experience with depression has on these scores.
      Seventy-five subjects (19 with current depression, 21 with past depression, and
      35 healthy controls) assigned utility scores to each of 10 individual symptoms of
      depression, and three depression severity profiles. Utility scores were measured
      using the standard gamble technique. Mean utility scores were used to list the
      symptoms of depression from most to least undesirable. The three diagnostic
      groups were compared with respect to the magnitude of undesirability of the
      depressive symptoms. The results of this study found that individuals assigned
      different utility scores to different symptoms of depression. The psychological
      symptoms of depression such as suicidal ideation, guilt and depressed mood were
      ranked as more undesirable than the somatic symptoms of depression. Each
      diagnostic group ranked the symptoms of depression in a similar manner. Patients
      with a current depression were willing to accept a greater risk of death to avoid
      suffering from lifelong depressive symptoms as compared to patients with a past
      depression or healthy controls.

PMID- 12057831
TI  - Event-related potentials elicited by stimulus spatial discrepancy in humans.
AB  - Sixteen subjects were instructed to discriminate whether the spatial locations of
      two visual stimuli presented in sequence were identical and event-related
      potentials (ERPs) were recorded from their scalps. The first and the second
      stimuli were presented in the same location in condition 1, but were in different
      locations in condition 2. ERP components of P100, N150, late positive component
      (LPC) and slow negative wave (SNW) were recorded in condition 1; in condition 2,
      N150 was enhanced and N270 was elicited before LPC. N150, N270 and SNW were all
      mainly distributed bilaterally over P3, P4, Pz, O1, O2, and Oz. N270 represents
      the brain activity for processing spatial discrepancy. There are several
      specialized brain areas involved in the generation of the N270.

PMID- 12057832
TI  - Resistive loaded breathing has a functional impact on maximal voluntary
      contractions in humans.
AB  - Resistive loaded breathing (RL) can modulate the electromyogram pattern during an
      isometric arm flexion or leg extension at 70-80% of voluntary maximal contraction
      (MVC). This study tested the hypothesis that an interaction between the
      respiratory muscle afferent activity during RL and the descending motor drive may
      also have a functional impact on voluntary maximal performance. Therefore, muscle
      contractions (100% of MVC) were performed with four muscles during phase specific
      expiratory (ERL) or inspiratory (IRL) resistive loading and force or the
      steadiness of the force produced were compared with non-RL controls. Both IRL and
      ERL reduced MVC in leg muscles, especially biceps femoris. IRL caused a reduction
      in steadiness in the same muscle. These results suggest a hitherto understated
      impact of RL on functional performance in leg muscles.

PMID- 12057833
TI  - Toluene-induced, Ca(2+)-dependent vesicular catecholamine release in rat PC12
      cells.
AB  - Acute effects of toluene on vesicular catecholamine release from intact PC12
      phaeochromocytoma cells have been investigated using carbon fiber microelectrode
      amperometry. The frequency of vesicles released is low under basal conditions and
      is enhanced by depolarization. Toluene causes an increase in basal release
      frequency. The threshold effect is obtained at 30 microM toluene and the maximum
      enhancement of basal release is seven-fold at 1 mM toluene. Toluene-induced
      exocytosis depends on the influx of Ca(2+) through voltage-activated Ca(2+)
      channels, which are blocked by Cd(2+). Toluene neither affects depolarization
      evoked exocytosis, nor the characteristics of release events. It is concluded
      that toluene-induced vesicular catecholamine release is due to an increase in
      intracellular Ca(2+) concentration, whereas basic processes underlying exocytosis
      do not appear to be affected by toluene at concentrations up to 300 microM.

PMID- 12057834
TI  - Nociceptin/orphanin FQ inhibits glutamate release from rat cerebellar and brain
      stem slices.
AB  - We have previously demonstrated that nociceptin/orphanin FQ (N/OFQ), inhibits
      K(+) depolarisation-evoked glutamate release from rat cerebrocortical slices. In
      this study we have examined the effects of N/OFQ on glutamate release from rat
      cerebellar and brain stem slices as there are regional differences in
      nociceptin/orphanin FQ receptor (NOP) expression. Slices were depolarised with
      two pulses of 46 mM K(+) (S(1) and S(2)) with N/OFQ added after S(1). Glutamate
      (non-radioactive) was measured using a fluorescence-based assay. N/OFQ effects
      were assessed by measuring area under S(1) and S(2) release curves and
      calculation of S(2)/S(1) ratios. In cerebellar slices K(+) evoked S(2)/S(1) ratio
      was 1.17+/-0.10 (n=28). This was reduced in a concentration dependent (EC(50) 22
      nM; E(max) 46%) and naloxone (10 microM) insensitive manner by N/OFQ. In the
      brain stem K(+) evoked glutamate release was considerably reduced compared to
      cerebellum. In several preparations K(+) failed to evoke a significant release.
      In those that did K(+) evoked S(2)/S(1) ratio was 1.03+/-0.07 (n=13). A total of
      100 nM N/OFQ reduced this by 38+/-12% and this response was naloxone insensitive.
      Due to this small response and its variability we could not construct a full
      concentration response curve. In conclusion we have demonstrated a functional NOP
      in rat cerebellum and brain stem that inhibits the release of glutamate.

PMID- 12057835
TI  - Effect of monensin on the levels of tachykinins and their processing enzyme
      activity in rat dorsal root ganglia.
AB  - Th effect of monensin, which inhibits trans-Golgi function, on the levels of
      tachykinins and their processing enzyme activity was examined in organ-cultured
      rat dorsal root ganglia (DRG). Using an enzyme immunoassay method, we measured
      neurokinin A and substance P immunoreactivity in the DRG cultured for 72 h with
      and without 0.1 microM monensin. Both tachykinins were reduced in the DRG treated
      with monensin. Treatment with monensin also reduced the activity of
      carboxypeptidase E, which is one of the proteolytic processing enzymes of
      neuropeptides. These data suggest that proteolytic processing enzymes may in part
      modulate the biological activity of neuropeptides within a trans-Golgi apparatus.

PMID- 12057836
TI  - Internal stochastic resonance in the coherence between spinal and cortical
      neuronal ensembles in the cat.
AB  - Internal stochastic resonance is a phenomenon in which the coherence of a non
      linear system is enhanced by the presence of a particular, non-zero level of
      noise generated by internal or external sources without a periodic input signal.
      The aim of this study was to demonstrate the experimental occurrence of internal
      stochastic resonance in the coherence between spinal and cortical neuronal
      ensembles. Simultaneous recordings of spinal and cortical evoked potentials were
      made in the somatosensory system of the anaesthetized cat. Evoked potentials were
      produced by input noise introduced in the tactile stimulation of the hindpaw
      skin. Coherence between the spinal and cortical evoked activity recorded during
      different levels of input noise was calculated. All animals showed distinct
      internal stochastic resonance like behavior. We found that the mean coherence was
      an inverted U-like function of the level of input noise with a mean coherence
      peak of 0.43. To our knowledge, this is the first documented evidence of such
      phenomenon in an in vivo preparation of the central nervous system.

PMID- 12057837
TI  - Mouse model of optic neuropathy caused by mitochondrial complex I dysfunction.
AB  - We developed a mouse model of optic neuropathy caused by mitochondrial complex I
      dysfunction by intravitreal administration of rotenone, a complex I inhibitor, in
      CBA/J mice. Retinal thickness was measured in sections stained histochemically
      for complex I enzymatic activity. The retinal ganglion cell layer of eyes
      injected with rotenone was significantly thinner than that of the control eyes
      injected with the vehicle dimethyl sulfoxide at 1, 24, and 48-h survival time
      groups. The largest reduction was 43% at 24-h post-injection. This effect is
      consistent with the degeneration of retinal ganglion cells in Leber's hereditary
      optic neuropathy. This is the first animal model of optic neuropathy caused by
      mitochondrial dysfunction, and it could be used as a quick and convenient way to
      test new treatments for mitochondrial neurodegenerative diseases.

PMID- 12057838
TI  - Detection of hypothalamic activation by manganese ion contrasted T(1)-weighted
      magnetic resonance imaging in rats.
AB  - To examine the usefulness of Mn(2+) contrasted magnetic resonance imaging (MRI)
      in hypothalamic imaging, images obtained using T(1)-weighted MRI were compared
      with Fos expression, which is known to increase after activation of voltage
      dependent Ca(2+) channels. Intravenous infusion of MnCl(2) elicited a rapid
      increase in the T(1)-weighted MRI signal intensity in the vessels and ventricles,
      but not in the brain parenchyma, suggesting that Mn(2+) did not diffuse freely
      across the blood-brain barrier. When the blood-brain barrier was broken by right
      intracarotid arterial injection of 25% D-mannitol, an increased signal intensity
      was seen in the right brain. Intracarotid arterial injection of hypertonic NaCl
      elicited rapid and striking increases in signal intensity in the paraventricular
      hypothalamic nucleus, supraoptic nucleus, and preoptic area, which are thought to
      be involved in central osmotic regulation. These observations were consistent
      with the Fos expression results. These results indicate that Mn(2+) contrasted
      MRI is a useful technique for investigating the autonomic center in the
      hypothalamus.

PMID- 12057839
TI  - An anti-Parkinson's disease drug, N-propargyl-1(R)-aminoindan (rasagiline),
      enhances expression of anti-apoptotic bcl-2 in human dopaminergic SH-SY5Y cells.
AB  - N-Propargyl-1(R)-aminoindan (rasagiline) is now under phase III clinical trials
      for Parkinson's disease (PD), and it rescues dopamine neurons from cell death in
      animal and cellular models of PD. Recently, we proved that rasagiline protected
      dopaminergic SH-SY5Y cells against apoptosis induced by a dopaminergic
      neurotoxin, N-methyl(R)salsolinol, and the mechanism was clarified to be due to
      suppression of death signal transduction in mitochondria. In this paper, the
      effects of rasagiline on the levels of anti-apoptotic bcl-2 gene family were
      studied. Rasagiline increased the levels of bcl-2 and bcl-x(l) mRNA at 100-10 nM
      and 100-10 pM, but not the level of pro-apoptotic bax mRNA. Enhanced expression
      of bcl-2 family indicates the ability of rasagiline to adjust the apoptotic
      threshold and protect degenerating neurons in PD.

PMID- 12057840
TI  - A novel role for melatonin: regulation of the expression of cell adhesion
      molecules in the rat hippocampus and cortex.
AB  - Neural cell adhesion molecules (NCAMs) are members of the immunoglobulin
      superfamily and are involved in synaptic rearrangements in the mature brain.
      There are three major NCAM forms: NCAM 180, NCAM 140 and NCAM 120. Several
      studies report that NCAMs play a central role in memory. In the present study we
      investigated the effects of melatonin on the expression of NCAMs in the
      hippocampus, cortex and cerebellum. The levels of NCAMs were determined by
      Western blotting. After administration of melatonin for 7 days, NCAM 180
      expression increased both in the hippocampus and in the cortex as compared to
      controls. On the contrary, in rats exposed to the constant light for 7 days
      (which inhibits endogenous production of melatonin), NCAM 180 levels decreased in
      the hippocampus and became undetectable in cortex and cerebellum. NCAM 140 levels
      were also diminished in the hippocampus of constant light-exposed rats. There was
      no change in NCAM 120 expression in any brain regions. This is the first report
      indicating that melatonin has a modulatory effect on the expression of NCAM in
      brain areas concerned with cognitive function. Melatonin may be involved in
      structural remodeling of synaptic connections during memory and learning
      processes.

PMID- 12057841
TI  - The neurokinin-2 receptor is not involved in the sensitization of primary
      afferents of the rat knee joint.
AB  - Using electrophysiological methods, we aimed in the present study to determine
      whether the NK(2) receptor is involved in the sensitization of articular
      afferents of the rat. Impulse activity from 27 single fine nerve fibres
      innervating knee joints was recorded during non-noxious and noxious joint
      rotations. Close intraarterial application of the NK(2) receptor agonist [beta
      Ala(8)]NKA(4-10) at doses of 0.2-200 nmol did not sensitize the afferents from
      normal knee joints to mechanical stimuli whereas the application of substance P
      (20 nmol) increased their mechanosensitivity. These data further support the
      hypothesis that the NK(2) receptor is not involved in the sensitization of
      primary afferents in normal knee joints to mechanical stimuli.

PMID- 12057842
TI  - Advanced glycation end products (AGE) and their receptor (RAGE) in the brain of
      patients with Creutzfeldt-Jakob disease with prion plaques.
AB  - The objective of this study was to assess the pathological role of advanced
      glycation end products (AGE) and the receptor for AGE (RAGE) in Creutzfeldt-Jakob
      disease (CJD). We immunohistochemically investigated the occipital lobe of three
      patients with CJD containing with prion protein (PrP) plaques using anti-AGE and
      RAGE antibodies. Many PrP-positive plaques were observed in these patients, and
      the PrP-positive prion plaques also showed immunoreactivity for the anti-AGE
      antibody. Furthermore, many astrocytes contained-PrP positive granules, and the
      same astrocytes also contained many AGE- and RAGE-immunopositive granules. The
      staining pattern of these granules showed good concordance with that of PrP.
      These findings suggest that there may be a RAGE-mediated PrP degradation pathway
      in CJD as is the case for beta-amyloid protein in Alzheimer's disease.

PMID- 12057843
TI  - Withdrawal from chronic ethanol increases the sensitivity of presynaptic 5-HT(1A)
      receptors modulating serotonin and dopamine synthesis in rat brain in vivo.
AB  - The in vivo sensitivity of presynaptic 5-HT(1A) receptors (autoreceptors and
      heteroreceptors) modulating the synthesis of 5-hydroxytryptophan/serotonin (5
      HTP/5-HT) and 3,4-dihydroxyphenylalanine/dopamine (DOPA/DA) in rat brain was
      investigated after ethanol treatment and withdrawal. In saline-treated rats as
      well as in acute ethanol (2 g/kg, intraperitoneally (i.p.), 2 h)- and chronic
      ethanol (2 g/kg for 7 days)-treated rats, a low dose of the 5-HT(1A) receptor
      agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT; 0.1 mg/kg, i.p., 1 h)
      did not decrease the synthesis of 5-HTP in brain (except modestly in striatum;
      20% after the chronic treatment) or that of DOPA in striatum. In contrast, in
      chronic ethanol-withdrawn rats (24 h), 8-OH-DPAT significantly decreased the
      synthesis of 5-HTP in the hippocampus (29%), cerebral cortex (41%) and striatum
      (33%) and that of DOPA in the striatum (28%). Similar effects were induced by the
      mixed 5-HT(1A) agonist/D(2) antagonist buspirone (1 mg/kg, i.p., 1 h) which also
      decreased 5-HTP synthesis in the hippocampus (24%), cerebral cortex (36%) and
      striatum (35%) of chronic ethanol-withdrawn rats. These results indicate that
      chronic ethanol and more clearly the spontaneous withdrawal from chronic ethanol
      induce supersensitivity of 5-HT(1A)-auto/heteroreceptors modulating the synthesis
      of 5-HT and DA in rat brain.

PMID- 12057844
TI  - Interferon-beta-1b increases serum interleukin-12 p40 levels in primary
      progressive multiple sclerosis patients.
AB  - Serum levels of interleukin-12 heterodimer (IL-12p70) and its homodimeric subunit
      (IL-12p40) were analyzed by enzyme-linked immunosorbent assay in 18 patients with
      primary progressive multiple sclerosis (MS) during 3 months before and 3 months
      under treatment with interferon-beta-1b (IFNbeta-1b, Betaferon(), eight million
      units (MIU) every other day subcutaneously). Median IL-12p40 levels in MS
      patients before treatment (66.5 and 63.9 pg/ml) were not elevated compared to 18
      healthy controls. IL-12p40 significantly increased during treatment (P<0.0001,
      median 105.3 pg/ml after 1 month and 95.3 pg/ml after 3 months). Detectable serum
      levels of IL-12p70 before therapy were only found in one patient. IL-12p70 did
      not increase during treatment. These data show that immunological processes may
      also play a role in primary progressive MS and that IFNbeta-1b has an
      immunomodulating effect in this particular MS subtype.

PMID- 12057845
TI  - Increased and type II-specific expression of peptidylarginine deiminase in
      activated microglia but not hyperplastic astrocytes following kainic acid-evoked
      neurodegeneration in the rat brain.
AB  - Peptidylarginine deiminases (PADs) are a group of posttranslational modification
      enzymes that convert protein arginine residues to citrulline residues. In the rat
      cerebrum, the type II PAD is thought to be expressed mainly in glial cells,
      especially astrocytes, and to become activated early in the neurodegenerative
      process. To determine whether hyperplastic glial cells express PAD type II, we
      examined the rat brain after kainic acid-evoked neurodegeneration. Western blot
      and reverse transcriptase-polymerase chain reaction analyses revealed increased
      and type II-specific expression of PAD in the brain at 4-7 days after kainate
      administration. Immunocytochemically, no PAD type II immunoreactivity was
      observed in the glial fibrillary acidic protein-positive astrocytes, but such
      immunoreactivity was present coincident with a microglial marker recognized by
      Bandeiraea simplicifolia isolectin B4 in the damaged regions. These results
      clearly indicate that PAD type II is specifically and abundantly expressed in
      activated microglial cells and suppressed in hyperplastic astrocytes following
      neurodegeneration.

PMID- 12057846
TI  - Physical activity increases the dissociation between subjective sleepiness and
      objective performance levels during extended wakefulness in human.
AB  - The process of heat loss has been shown to be a key pathway regulating sleepiness
      in humans. The influence of physical exercise with its attending heat production
      on subjective sleepiness and performance levels during total sleep deprivation
      (SD) was assessed in eight healthy young volunteers (mean age 21.1 years). Each
      subject participated in a SD cross-over study in which sleepiness and performance
      levels were tested under exercise and non-exercise conditions. The exercise
      entailed 15 min walking/h (3.0 Kcal/kg per h caloric consumption). Physical
      exercise significantly alleviated subjective sleepiness depending on the
      magnitude of the core body temperature elevation. This indicates that suppressing
      heat loss could prevent progression of subjective sleepiness during the
      nighttime. We found a strong positive correlation between increased sleepiness
      and decreased performance levels in each of the two experimental sessions.
      However, ANCOVA revealed a significant difference in the slope of the regression
      lines representing two sessions, indicating less subjective sleepiness with
      physical exercise despite the same decrease in performance. The present findings
      alert us to the possibility that increased physical activity during extended
      wakefulness could increase the dissociation between subjective evaluation of
      sleepiness and actual brain function, resulting in increased risk of human error.

PMID- 12057847
TI  - Morphological changes of cerebral arteries in a canine double hemorrhage model.
AB  - Cerebral vasospasm is a major cause of morbidity and mortality in patients
      suffering from subarachnoid hemorrhage (SAH). Despite numerous studies, the
      pathogenesis of this deadly disorder is not clearly understood. Alterations in
      endothelial cells are a distinct morphological feature of cerebral vasospasm and
      some recent studies suggest that apoptosis might play a role in the cells' death.
      The goal of the present study is to examine the time course of apoptosis in
      endothelial cells of spastic cerebral arteries following experimental
      subarachnoid hemorrhage. Fifteen dogs were used in the present study. Twelve of
      them were divided into three groups (four per group) and subjected to a double
      hemorrhage method of SAH. Following SAH, groups were sacrificed respectively on
      days 3, 5, and 7. Three dogs served as controls without blood injection. The
      basilar arteries were studied with the transmission electron microscopy and with
      angiography. Angiographic vasospasm began on day 3 and peaked on day 7. In
      morphologic studies, control dogs did not demonstrate apoptotic-like changes in
      endothelial cells of the basilar arteries. Beginning with day 3, apoptotic-like
      changes were noted in endothelial cells and consisted of condensation of
      peripheral nuclear chromatin, blebbing of the cell membrane, and condensation of
      the cytoplasm. Such changes progressed with time and were maximally developed by
      day 7. This is the first study that demonstrates the time course of apoptotic
      like changes in the endothelial cells in the vasospastic basilar artery.
      Apoptosis might play an important role in the pathogenesis of vasospasm.

PMID- 12057848
TI  - Attenuation of retinal photooxidative damage in thioredoxin transgenic mice.
AB  - Thioredoxin (TRX) is an endogenous redox (reduction/oxidation) regulator that has
      cytoprotective effects against various types of oxidative stresses. Exposure to
      excessive levels of white light induces retinal photoreceptor damage. To test the
      cytoprotective effect of overexpressed TRX against retinal photooxidative damage,
      both TRX transgenic (trx-tg) mice and C57BL/6 (wild type) mice were exposed to
      intense white fluorescent light. The amounts of oxidized and tyrosine
      phosphorylated proteins decreased in the neural retinas of the trx-tg mice
      compared to the wild type mice after light exposure. The electroretinographic
      amplitudes were higher and the formation of oxidized DNA was lower in trx-tg mice
      compared to wild type mice after light exposure. These results suggest that
      overexpression of TRX suppresses retinal photooxidative damage. TRX
      intensification may be a useful therapeutic strategy to prevent retinal photic
      injury.

PMID- 12057849
TI  - Stem cells on the way to restorative medicine.
AB  - Stem cells are defined by their unique properties of self-renewal and
      multilineage differentiation. Several decades ago, cells with such developmental
      plasticity have been identified in the embryo and in the bone marrow of the
      adult; in other organs, such cells could not be demonstrated. Here, recent
      findings are briefly summarized indicating that the elementary stem cell
      capabilities are retained by a limited number of cells present in many organs of
      the adult. Other data suggest that, on response to another microenvironment,
      "organ-specific" stem cells are able to acquire different fates. If confirmed
      these findings will have considerable impact on the future of clinical stem cell
      therapy.

PMID- 12057850
TI  - Interleukin-12-gene transduction makes DCs from tumor-bearing mice an effective
      inducer of tumor-specific immunity in a peritoneal dissemination model.
AB  - Dendritic cells (DCs) from cancer patients, as well as tumor-infiltrating DCs,
      are reported to have suppressed immunostimulatory capacity. One of the major
      problems in the clinical use of DCs for treating tumors is that the DCs must be
      autologous ones obtained from patients. Compared with normal DCs (nDCs), flow
      cytometric analysis and allogeneic mixed lymphocyte reaction (MLR) have revealed
      lower expression of the costimulatory molecules and suppressed T-cell-stimulatory
      activity in DCs derived from tumor-bearing mice (tDCs) despite of culture. We
      reported previously that the interleukin-12 (IL-12)-gene-transduced nDCs
      inhibited tumor growth due to induced tumor-specific Th1 and cytotoxic T cells
      (CTLs) in a murine established subcutaneous tumor model. In the present study, we
      examined whether tDCs could induce immune responses against tumors after IL-12
      gene transduction in an established peritoneal dissemination model. The
      intraperitoneal injection of IL-12-gene-transduced tDCs resulted in prolonged
      survival of some treated mice (log-rank test; P=0.001) and tumor-specific Th1 and
      CTL activity. The injection of IL-12-gene-transduced nDCs prolonged the survival
      of all treated mice (P<0.0001) and elicited tumor-specific immunity, which were
      better than those of IL-12-gene-transduced tDCs. Taken together, DC modification
      of IL-12-gene transduction is an effective and promising approach for cancer
      therapy even when immunosuppressive tDCs are employed.

PMID- 12057851
TI  - Identification of HLA-A24-restricted CTL epitope encoded by the matrix protein
      pp65 of human cytomegalovirus.
AB  - The activation of a specific cellular immune response against human
      cytomegalovirus (CMV) is an important key factor to solving CMV infection after
      bone marrow transplantation (BMT). In the present study, our purpose was to
      identify the HLA-A24-restricted cytotoxic T cell (CTL) epitope from the CMV
      immunogenic matrix protein pp65. We selected five CMV pp65 peptides with HLA-A24
      binding motif from the HLA peptide binding predictions web site. Peptide binding
      assay was performed using biotinylated HLA-A24-restricted MAGE-1 peptide as a
      reference peptide and transporter associated with antigen processing (TAP)
      deficient T2-A24 cells expressing high level of HLA-A24 protein as target cells.
      After co-incubation of biotinylated MAGE-1 and titrated amounts of competitor
      peptides with T2-A24 cells, the binding of each peptide was analyzed on a flow
      cytometer. Peptide binding assay showed that three out of five peptides derived
      from CMV pp65 bound to T2-A24 cells with various affinity levels. CTL induction
      assay using peptide-pulsed DC derived from eight HLA-A24(+) donors revealed that
      the peptide (QYDPVAALF) with the highest affinity was able to elicit potent CTLs
      which killed peptide-pulsed TISI cells. These CTLs were found to show the killing
      activity against human fibroblast cells transduced with both HLA-A*2402 and CMV
      pp65 cDNAs, and CMV-infected HLA-A24(+) fibroblast cells. These results suggested
      that the peptide (QYDPVAALF) is one of HLA-A24-restricted CTL epitope derived
      from CMV pp65 protein and may be of therapeutic value in peptide-based vaccines
      against CMV infection in BMT patients.

PMID- 12057852
TI  - MCP-1 and MIP-2 response in Trichinella spiralis infected mice treated with 4
      deoxypyridoxine (4-DPD).
AB  - Chemokines are involved in a number of pathophysiological conditions, such as
      inflammatory processes and are divided in two major subfamilies, C-X-C and C-C
      chemokines. The C-C chemokines are monocyte chemotactic protein 1-2-3-4-5, while
      C-X-C chemokines include MIP-2, IL-8, etc. We studied the levels of MCP-1 and MIP
      2 in diaphragmatic and intercostal muscle tissue and serum in Trichinella
      spiralis infected mice treated and not treated with 4-deoxypyridoxine, a potent
      Vit. B6 antagonist which inhibits humoral and cellular immune response. MCP-1 and
      MIP-2 were measured in homogenized tissue and serum and determined by a specific
      ELISA. Here we found the levels of MCP-1 and MIP-2 in diaphragmatic and
      intercostal muscle tissue of T. spiralis infected mice were significantly
      increased after 10 days and peaked on day 20 post-infection; however, the levels
      of MIP-2 in mice treated with 4-DPD was lower than that of untreated mice at day
      20. MCP-1 also peaked at days 20 and 40. Animals treated with 4-DPD also
      inhibited the production of MCP-1, compared with untreated animals. The maximum
      inhibition was at day 40. These inhibitory effects on MIP-2 and MCP-1 were also
      repeated in the serum determinations, but were not significant. This study
      demonstrates that MIP-2 and MCP-1 are stimulated in serum and tissue of T.
      spiralis infected mice and 4-DPD-treated animals significantly inhibited them.

PMID- 12057853
TI  - Age-related accumulation of memory cells in mouse Peyer's patches.
AB  - The development of memory cells seems to take place in the germinal centres,
      which are chronically present in Peyer's patches (PPs). We report here age
      associated changes in the lymphocyte compartment and in the number of PPs of
      unimmunised mice. Mice 4 weeks old do not exhibit well constituted germinal
      centres, but just only 1 week later, the mice develop a normal germinal centre
      reaction, which is maintained until late ages (mice 30 weeks old), to decrease
      thereafter in older mice. In addition, we also show that memory cells accumulate
      in PPs in old mice, being the main population CD44(+) CD62L(-) CD49d(+) CD40(+)
      CD25(-) B cells. These data suggest that memory B cells tend to accumulate in PPs
      in ageing mice, even when the GC reaction has already decreased.

PMID- 12057854
TI  - Stromal cell derived factor 1 synthesis by spleen cells in rodent malaria, and
      the effects of in vivo supplementation of SDF-1alpha and CXCR4 receptor blocker.
AB  - The mechanisms of malaria parasite clearance in the host are not well understood,
      but are ascribed to the intact spleen, the site for parasite clearance. The
      infection induces a huge increase in spleen volume and cellularity. There is,
      however, a lack of studies on the splenic production of chemokines, which are
      small proteins that control homing and activation of immune cells and must be
      crucial for organized tissue growth. We studied the spleen cell production of SDF
      1, a primordial chemokine of the CXCL12 class, through mRNA Reverse transcriptase
      and polymerase chain reaction of both isoforms, alpha and beta, in lethal
      (Plasmodium berghei ANKA) and non-lethal recrudescent malaria (Plasmodium
      chabaudi CR) in BALB/c and C57BL/6 mouse strains. In non-lethal P. chabaudi
      malaria in C57BL/6 mice, SDF-1alpha mRNA production clearly peaked before the
      control of parasitemia, a fact not observed in the same mouse strain infected
      with lethal P. berghei, when this production was lower and without peaks. The
      infection of BALB/c mice infected with the same Plasmodium species led to a
      similar evolution of parasitemia and also chemokine production, albeit at lower
      levels. SDF-1beta synthesis was more constant and regular during both infections,
      presenting some variation but usually occurring at all the experimental times.
      Supplementation of lethal models with SDF-1alpha i.p., at the time when
      endogenous stromal cell chemokine production peaked in non-lethal models, induced
      a clear reduction in parasitemia, probably with prolonged host survival. Blocking
      SDF-1 action by administration of T-140, a CXCR4 receptor blocker, caused an
      increase in circulating parasites in the usually benign non-lethal P. chabaudi
      malaria in C57BL/6 mice, mainly at recrudescence of parasitemia. These data
      suggest that SDF-1alpha production in the spleen plays an important role in
      rodent malaria, and its supplementation was found to partially correct defects in
      the control of malaria in lethal models.

PMID- 12057855
TI  - Study of diverse mechanisms of cell-mediated cytotoxicity in gene-targeted mice
      using flow cytometric cytotoxicity assay.
AB  - Cytotoxic lymphocytes kill tumor or virus-infected target cells utilizing two
      mechanisms-(1) release of lytic granules (containing perforin and granzymes), and
      (2) Fas ligand (FasL)/Fas or TNF-initiated apoptosis. We have examined mechanisms
      of target cell lysis by effector T cells from gene-targeted and mutant mice using
      a new Flow Cytometric Cytotoxicity Assay (FC Assay). Target cells were labeled
      with PKH67 dye. Cell death was estimated by 7-AAD inclusion and annexin V-PE
      binding. A direct correlation has been found between the percentage of dead
      target cells in FC Assay and the results of 111In release cytotoxicity assay when
      effector T cells from either Pfp -/- (perforin knockout) or gld (non-functional
      Fas Ligand) mice were used. As shown by the 4 h FC assay, the granule-mediated
      mechanism was utilized by T cells from gld mice. In contrast, T cells from Pfp -/
      mice used death receptor-mediated lysis. Therefore, cytotoxic cells from gene
      targeted and mutant mice can serve as valuable tools for studying different
      mechanisms of cell-mediated cytotoxicity, and the FC assay could be applied
      irrespective of which cytotoxic effector pathway is involved.

PMID- 12057856
TI  - Characterization of B-1b cells as antigen presenting cells in the immune response
      to gp43 from Paracoccidioides brasiliensis in vitro.
AB  - Antigen presentation is an essential stage in the development of immune response
      to a specific antigen. This response can lead to the production of antibodies
      and/or effector T lymphocyte activation. Macrophages, dendritic cells and B
      lymphocytes, among others, act as antigen presenting cells. B-lymphocytes capture
      antigenic particles through a surface receptor of IgM nature. The interaction IgM
      antigen leads to endocytosis of the complex and antigen processing which
      culminates in presentation of the antigen on the cell surface associated with a
      class II MHC molecule. At least three B cell subsets, B-1a (Ly-1B), B-1b and B-2,
      are present in the mouse periphery. B-1a and B1-b cells represent a small
      population in the adult spleen and are abundant in the peritonial and pleural
      cavities. It has been demonstrated in our laboratory that B-1b cells
      spontaneously proliferated in stationary cultures of adherent peritonial cells.
      Further, that these cells migrate to a non-specific inflammatory focus. Based on
      these findings, we investigated whether these cells are antigen presenting cells
      in vitro using as antigenic stimulus gp43 from Paracoccidioides brasiliensis.
      Results showed that B1-b cells express constitutively high levels of class II MHC
      and costimulatory molecules inducing an efficient proliferation of gp43
      sensitized T lymphocytes.

PMID- 12057857
TI  - A major nucleolar protein B23 as a marker of proliferation activity of human
      peripheral lymphocytes.
AB  - A novel monoclonal antibody (Mab) (called 3C9) against a major nucleolar
      phosphoprotein B23 was used to study B23 qualitative and quantitative alterations
      in phytohemagglutinin (PHA) -stimulated human peripheral blood lymphocytes in
      indirect immunofluorescence and Western blots. It was shown that lymphocyte
      proliferation was accompanied by gradual augmentation of nucleoli and their
      accumulation of the protein B23 up to 2-fold by 16 h and 40-50 fold by 72 h, as
      compared with the non-stimulated cells. By parallel immunolabeling with the anti
      Ki-67 antibody, it was shown that the early changes of B23 amount and
      localization occurred before an appearance of Ki-67 protein, a well-known marker
      of proliferating cells. Our results evidence that antibodies against B23 might be
      applied for recognition of human peripheral lymphocytes at early stages of their
      activation for proliferation, preceding the S-phase.

PMID- 12057858
TI  - Human GlyCAM-1 mRNA is expressed in the mammary gland as splicing variants and
      encodes various aberrant truncated proteins.

PMID- 12057859
TI  - Whole body FDG-PET for the evaluation and staging of small cell lung cancer: a
      preliminary study.
AB  - [F18]-2-deoxy-2fluoro-D-glucose positron emission tomography (FDG-PET) is
      increasingly used in the diagnosis and staging of lung cancer. Despite its
      positive performance characteristics in non-small cell lung cancer (NSCLC), the
      role of FDG-PET in the staging of small cell lung cancer (SCLC) remains to be
      determined. We designed a prospective study to address this question. Eighteen
      patients with SCLC were enrolled prospectively to undergo total body FDG-PET in
      addition to conventional staging procedures (chest computed tomography (CT),
      abdominal CT, cranial CT or magnetic resonance imaging (MRI), and bone scan/bone
      marrow biopsy). The agreement between FDG-PET and conventional staging modalities
      in identifying the presence or absence of metastatic disease was compared using
      the Veterans Administration (VA) cooperative staging system for staging. Overall
      staging by FDG-PET agreed with conventional staging exams in 15/18 (83%) patients
      (kappa=0.67), which included eight extensive and seven limited cases. FDG-PET
      showed more extensive disease in two of the three patients for which FDG-PET and
      conventional staging disagreed. These data suggest that total body FDG-PET may be
      useful in the staging, treatment planning, and prognostication of SCLC. Whether
      FDG-PET will replace other more established staging modalities remains to be
      determined by larger prospective randomized controlled studies.

PMID- 12057860
TI  - FDG-PET imaging in small cell lung cancer: any value?

PMID- 12057861
TI  - Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine
      (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase
      III randomised trial.
AB  - PURPOSE: The combination of Gemcitabine (GEM)/carboplatin (CBDCA) has
      demonstrated activity in the treatment of stage III and IV non-small-cell lung
      cancer (NSCLC). This phase III randomized trial compared the response rate,
      survival rate, and toxicity of the combination of GEM plus CBDCA with the
      combination of VLB plus CDDP. METHODS: Chemonaive patients with advanced or
      metastatic NSCLC were enrolled in the study. Pts were randomized by coin method
      to receive either cisplatin (CDDP) 70 mg/m(2) on day 1 plus vinblastine (VLB) 6
      mg/m(2) on days 1 and 8 (arm A) or gemcitabine 1000 mg/m(2) on days 1 and 8 plus
      carboplatin 300 mg/m(2) on day 1 (arm B). Both regimens were administered on a 21
      day course. RESULTS: A total of 198 patients (99 pts each in arms A and B) were
      enrolled in the study between July 1997 and April 2000. All pts had an ECOG
      performance status < or=2. Patients had a median age of 58 years (range, 49-67)
      in arm A and 59 years (range, 49-69) in arm B. In arm A, there were 15 partial
      responders (PR), for an overall response rate (ORR) of 15%, compared with three
      complete responders (CR) and 24 PR, for an ORR of 27% (P<0.05), in arm B. Mean
      survival times were 7.9 months (95% CI, 7.1-8.0) in arm A and 11.6 months (95%
      CI, 10.0-13.0) in arm B. One-year survival rates for arms A and B, respectively,
      were 13 and 36%. Numbers of pts with WHO grad 3/4 hematologic and non-hematologic
      toxicity in arms A/B were leukopenia 0/2, thrombocytopenia 0/2, alopecia 46/33,
      neurotoxicity 2/1, and asthenia 35/42. CONCLUSION: The GEM/CBDCA combination
      showed a higher therapeutic response, an improved 1-year survival, and a similar
      toxicity profile compared with the VLB/CDDP combination.

PMID- 12057862
TI  - Chemotherapy of advanced non-small cell lung cancer: any standard treatment?

PMID- 12057863
TI  - Non-small cell lung cancer clinical trials with trastuzumab: their foundation and
      preliminary results.
AB  - The overexpression of HER2, a transmembrane glycoprotein tyrosine kinase, has
      been implicated in mitogenesis, cell survival, invasion and angiogenesis.
      Preclinical evidence suggests that HER2 overexpression contributes to tumor
      progression in non-small cell lung cancer (NSCLC) and retrospective clinical
      correlative studies show that it is probably associated with poor clinical
      outcome. Trastuzumab (Herceptin, Genentech Inc., South San Francisco, CA) is a
      recombinant humanized monoclonal antibody that targets HER2 and is currently
      approved for use in the treatment of patients with HER2-overexpressing metastatic
      breast cancer. Two primary mechanisms proposed for the activity of trastuzumab
      are downregulation of HER2 and induction of antibody-dependent cell-mediated
      cytotoxicity. Evidence from preclinical studies of trastuzumab in NSCLC and other
      cell lines, the presence of HER2 overexpression in NSCLC clinical specimens and
      the clinical benefit derived from trastuzumab in phase II and III metastatic
      breast cancer trials have led to the development of clinical trials of
      trastuzumab in NSCLC. Phase II studies of trastuzumab in patients with stage IIIB
      or IV NSCLC are being conducted to test the efficacy of trastuzumab as a single
      agent or in combination with chemotherapy. Preliminary results show combinations
      of chemotherapy plus trastuzumab are well tolerated, with encouraging response
      rates of 21-40%. A randomized phase II trial of chemotherapy with or without
      trastuzumab showed promise in a small subgroup of patients with 3+ HER2
      overexpression by immunohistochemistry or HER2 DNA amplification by fluorescence
      in situ hybridization. Taken together, these data indicate that trastuzumab
      warrants further investigation in a clinical study in selected patients with
      NSCLC.

PMID- 12057864
TI  - Pet birds and risk of lung cancer in North-Western Germany.
AB  - In a case-control study on lung cancer and occupational exposures, a subgroup of
      144 cases and 253 population-based controls interviewed in the last 16 months of
      the study, were additionally asked about their exposure to pet birds and other
      pets. We used the same questionnaire as a previous German study that found a
      positive association between pet bird keeping and lung cancer. Odds ratios were
      calculated for lifetime and adulthood exposure respectively. The adjusted odds
      ratio for ever keeping pet birds was 0.85 (95% CI: 0.53-1.35), and 0.87 (95% CI:
      0.56-1.36) for adulthood exposure. There was no evidence of a trend for
      increasing lung cancer risk with duration of pet bird keeping. With decreasing
      age at diagnosis, an apparent risk emerged, yielding an odds ratio of 7.62 (95%
      CI: 2.15-26.95) for ever versus never in the youngest age group (< or =55 years).
      This odds ratio was reduced to 3.82 (95% CI: 0.98-14.92) after adjustment for
      smoking and was only 1.39 (95% CI: 0.49-3.95) for adulthood exposure. In general,
      our results indicate that pet bird keeping does not seem to increase the risk of
      lung cancer. The divergent findings at younger ages may be explained by age
      related recall bias, but should be investigated in future studies.

PMID- 12057865
TI  - A myeloperoxidase polymorphism associated with reduced risk of lung cancer.
AB  - Myeloperoxidase (MPO) is a metabolic/oxidative enzyme found in neutrophils and
      monocytes that contributes to pulmonary carcinogenesis through activation of
      specific procarcinogens including benzo[a]pyrene intermediates, 4-aminobiphenyl
      and the arylamines. There is a G-->A polymorphism located in the 5' untranslated
      region of the MPO gene that may be responsible for reduced transcriptional
      activity due to the decreased binding affinity for the SP1 transcription factor.
      Individuals with one or two copies of the A-allele may be afforded protection due
      to decreased transcriptional activity of MPO and subsequent decreased metabolic
      activation of procarcinogens. Previous studies have reported a range of
      protective effects in different ethnic populations. We employed a restriction
      fragment length polymorphism-polymerase chain reaction (RFLP-PCR) assay to
      identify the MPO genotypes in 375 lung cancer cases and 378 healthy controls, all
      of whom were Caucasian. Our results demonstrate a reduced risk of lung cancer
      when the A-allele genotypes (G/A+A/A) were combined (odds ratio (OR)=0.66; 95%
      confidence interval (CI) 0.49-0.90). We also noted a protective effect (OR=0.63;
      95% CI 0.45-0.87) in ever smokers with the A-allele genotypes which was not
      evident in never smokers (OR=1.14; 95% CI 0.42-3.11). We observed an incremental
      decrease in the protective effects as cigarette pack-years increased. Thus,
      lightest smokers were provided the greatest protection. When the data were
      stratified by gender, there was a statistically significant reduced risk of lung
      cancer among men (OR=0.55; 95% CI 0.36-0.84), but not among women (OR=0.81; 95%
      CI 0.55-1.26) for the A-allele genotypes. Lastly, an age effect was evident only
      in men but not women. The protective effects of the A-allele genotypes decreased
      with increasing age. This report provides further support for the hypothesis that
      a single nucleotide polymorphism in the MPO gene is a protective factor in lung
      cancer carcinogenesis.

PMID- 12057866
TI  - Human lung cancer cells and tissues partially recapitulate the homeobox gene
      expression profile of embryonic lung.
AB  - The fetal cell features of tumor cells suggest that neoplasia arises through a
      process of defective ontogeny. Homeobox (HOX) genes code for transcription
      factors that orchestrate organogenesis patterning and maintain tissue
      homeostasis. Thus, if detective ontogeny is a mechanism in cancer development, it
      can be hypothesized that tumor cells should express the HOX genes normally
      expressed by the embryonic cells of that tissue. Our data herein indicate that
      some HOX genes, whose expression is normally restricted to pulmonary
      embryogenesis, are re-expressed in lung cancer cells. However, lung cancer cells
      also frequently and inappropriately express HOX genes that are not normally
      expressed in lung tissue, regardless of developmental stage. Thus, whereas re
      expression of some of the embryo-specific HOX genes is a common feature of lung
      cancer, tumors do not faithfully recapitulate the expression pattern of cells
      that participate in the early stages of lung development.

PMID- 12057867
TI  - Regulation of E-cadherin/catenin complex patterns by epidermal growth factor
      receptor modulation in human lung cancer cells.
AB  - We previously demonstrated that a ligand-blocking monoclonal antibody (mAb)
      against the epidermal growth factor-receptor (EGF-R), LA1, induced morphological
      conversion from epithelial-like to epithelial of the human lung cancer cell line,
      H322. This was accompanied by an up-regulation of epithelial cadherin (E
      cadherin) expression (Clin. Cancer Res. 5 (1999) 681). In the present paper, we
      show that mAb LA1 induces the epithelial-like to epithelial conversion of the
      human lung cancer cell line, A549. In A549 and H322 cells, which express a
      detectable amount of EGF-R (ErbB-1), ErbB-2, ErbB-3, and ErbB-4 receptors, the
      LA1 mAb induces up-regulation of the E-cadherin/catenin complex (alpha-, beta-,
      and gamma-catenins). This is associated with re-localization of E-cadherin, alpha
      catenin, (and to a lesser extent beta-catenin), but not gamma-catenin.
      Additionally, we report that mAb LA1 inhibits cell motility. In contrast,
      epidermal growth factor (EGF) or heparin-binding EGF-like growth factor (HB-EGF)
      induces the epithelial-like to fibroblastoid conversion of A549 and H322 cell
      lines, slightly reduces the expression of E-cadherin and beta-catenin, but not
      alpha- and gamma-catenins, and stimulates cell motility. These studies
      demonstrate that EGF-R modulation regulates the E-cadherin/catenin complex and
      cell motility in human lung epithelial carcinoma cells. Our results may have
      important therapeutic implications for the treatment of invasive human lung
      carcinomas via the restoration of the cadherin/catenin complex using inhibitors
      of EGF-R.

PMID- 12057868
TI  - Elevated preoperative serum levels of angiogenic cytokines correlate to larger
      primary tumours and poorer survival in non-small cell lung cancer patients.
AB  - We have analysed the predictive and prognostic information in preoperatively
      collected serum levels of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) in patients clinically evaluated as operable non
      small cell lung cancer (NSCLC). Fifty-eight patients with operable NSCLC were
      included. VEGF and bFGF levels in serum were analysed using enzyme linked
      immunosorbent assays (Quantikine human VEGF and Quantikine HS human FGF basic,
      R&D Systems). Univariate analysis demonstrated that tumour volume, platelet
      counts, VEGF and bFGF were significant prognostic factors. However, only bFGF
      remained significant in the multivariate analysis (P=0.014). Significant
      correlation's were demonstrated between VEGF levels and tumour volume (r=0.33;
      P=0.012) and platelet count (r=0.43; P=0.001). bFGF levels correlated significant
      with recurrent disease (r=0.34; P=0.01), platelet count (r=0.53, P<0.001) and
      performance status (r=0.29; P=0.029). Furthermore, bFGF levels and VEGF levels
      correlated significantly (r=0.44; P<0.001). We conclude that elevated circulating
      angiogenic cytokines correlate with tumour volume, higher relapse risk and poorer
      survival in patients with operable non-small cell lung cancer.

PMID- 12057869
TI  - Postoperative adjuvant chemotherapy and radiotherapy for stage II and III non
      small cell lung cancer (NSCLC).
AB  - The role of postoperative adjuvant chemo-radiotherapy in the treatment of
      patients with non-small cell lung cancer (NSCLC) remains unclear. This study was
      undertaken to evaluate the survival outcomes, relapse patterns, prognostic
      factors and complications of postoperative adjuvant MVP chemotherapy and
      radiotherapy. The study involved some 96 patients who had undergone curative
      resection of stage II and III NSCLC between 1991 and 1996. Among these, 94
      patients who completed their adjuvant treatment were analyzed. Surgery consisted
      of pneumonectomy (33%), single lobectomy (54%) or bilobectomy (13%). Within 4
      weeks of curative resection, two cycles of MVP chemotherapy (mitomycinC 8
      mg/m(2), vinblastine 8 mg/m(2), cisplatin 60 mg/m(2)) were started at 4 weeks
      intervals. Conventionally fractionated radiotherapy was given 3 weeks after
      chemotherapy to a total dose of 50 Gy in completely resected patients and 55-60
      Gy in patients with positive resection margins. The TNM classification of the
      AJCC, as revised in 1997, was used for pathologic staging. The number of patients
      at AJCC stages IIa, IIb, IIIa, and IIIb were four, 40, 45, and five,
      respectively. A pathologically positive bronchial resection margin was found in
      nine patients. At the time of analysis, death was recorded in 29 patients (31%),
      though five had died without evidence of lung cancer. Overall 2, 3, and 5-year
      survival rates for all patients were 74.2, 70.2, and 65%, respectively, and
      locoregional disease-free survival (LRDFS) rates were 88.6, 83.7, 74.3%, at 2, 3,
      and 5-years, distant metastasis disease-free survival (DMDFS) rates were 67.7,
      65.0, and 63.6%, respectively. In the multivariate model, a primary tumor size of
      more than 5 cm and the level of pathologically positive nodes were found to be
      associated with poor overall survival, LRDFS and DMDFS. Although positive
      bronchial resection margin affected overall survival, LRDFS and DMDFS were
      unaffected. With respect to the first site of relapse, distant metastasis
      occurred more frequently (N=33, 35%) than locoregional recurrence (N=15, 16%).
      Grade 3 esophagitis in two patients and weight loss of more than 10% in five
      patients were observed during adjuvant treatment. Grade 4 pulmonary toxicity was
      observed in one patient after radiotherapy and this patient ultimately died 5
      months after treatment. The postoperative adjuvant MVP chemotherapy and
      radiotherapy regimen showed relatively low locoregional recurrence and distant
      metastasis rates and good survival with acceptable toxicity. A prospective
      randomized trial, which compares this regimen to surgery alone or postoperative
      adjuvant radiotherapy is needed.

PMID- 12057870
TI  - A phase II study testing paclitaxel as second-line single agent treatment for
      patients with advanced non-small cell lung cancer failing after a first-line
      chemotherapy.
AB  - The purpose of this study was to determine the activity of paclitaxel as a second
      line chemotherapy for non-small cell lung cancer (NSCLC). This multicentric trial
      included patients who had failed to a first-line chemotherapy with platinum
      derivatives and/or ifosfamide. After registration, patients were treated by
      paclitaxel i.v. at a dose of 225 mg/m(2) given over 3 h administered every 3
      weeks. Response was assessed after three courses of therapy. Sixty-seven patients
      were registered, one was ineligible and 64 were assessable for response. Two
      partial responses were observed (3% of the eligible patients; 95% confidence
      interval: 0-7%). No change was documented in 16 cases (24%). Tolerance was
      acceptable, the main toxicity being cumulative polyneuropathy. Median survival
      duration was 4.5 months with a 1-year rate at 19%. We concluded that paclitaxel
      is not active in terms of response as second-line chemotherapy for NSCLC.

PMID- 12057871
TI  - Long-term results of induction chemotherapy followed by concurrent chemotherapy
      and thoracic irradiation in limited small cell lung cancer.
AB  - BACKGROUND: Small cell lung cancer (SCLC) is a chemoresponsive tumor but overall
      survival remains poor even in limited disease (LD). With the aim of eradicating
      chemoresistant tumor cells and reducing toxicity, we investigated in this phase
      II trial the feasibility and outcome of a sequential approach of induction
      chemotherapy (CT) followed, in responding patients with LD-SCLC, by intensified
      platinum-based CT and concurrent thoracic irradiation (TI). MATERIALS AND
      METHODS: We treated 55 consecutive LD-SCLC patients with three 21-day cycles of
      cyclophosphamide, epiadriamycin and vincristine (CEV) as induction CT. In 44
      (80%) patients there was an objective response and they received treatment
      intensification consisting of TI and concomitant CT with carboplatin and
      etoposide plus recombinant granulocite colony stimulating factor. Twenty-five
      (57%) patients were submitted to twice-daily thoracic irradiation (TDTI; 1.5 Gy
      per fraction, to a total dose of 45 Gy) and 19 (43%) to once-daily thoracic
      irradiation (ODTI; 2 Gy per fraction, to a total dose of 50 Gy). RESULTS: Median
      follow up was 75 months (range, 42-102). Of 44 patients submitted to
      intensification with TI plus CT, 32 (73%) had a complete and 12 (27%) a partial
      response. Median overall survival of all 55 patients was 17 months with actuarial
      survival probabilities of 2 and 5 years, 32 and 25%, respectively. Analysis of
      patient sub-groups showed a 5-month median survival in non-responders, 19 in TDTI
      and 17 in ODTI patients, respectively. Two and 5 year survival probabilities were
      0% in non-responders, 40 and 35% in TDTI and 39 and 21% in ODTI patients,
      respectively. At present, 13 of 44 responders are still alive, of which nine
      (20%) have been progression-free from 45 to 93 months (median 60). Treatment
      failure was registered in 31 (70%) of 44 patients who received both induction and
      intensification treatment. One-half of patients had intrathoracic recurrence,
      eight of which only local and the remaining seven local and distant. Fourteen
      (32%) patients had brain metastases. Grade 3-4 neutropenia occurred in 24 (55%)
      patients with no differences between treatment groups. Grade 3 esophagitis was
      registered in four (9%) patients: in 3/25 (12%) and 1/19 (5%) of those who
      received TDTI and ODTI, respectively (P=not significant). Acute radiation
      pneumonitis occurred in three (12%) patients submitted to TDTI. No clinically
      debilitating pulmonary fibrosis, permanent esophageal stricture or toxic death
      was observed. CONCLUSIONS: In LD-SCLC patients late concurrent CT plus TI is
      feasible and effective. Our long-term results are similar to the best reported in
      the literature. Despite the high incidence of complete response obtained,
      however, one-half of the patients had intrathoracic relapse and one-third brain
      metastases.

PMID- 12057872
TI  - Treatment of brain metastases in patients with non-small cell lung cancer (NSCLC)
      by stereotactic linac-based radiosurgery: prognostic factors.
AB  - A restrospective study of patients with brain metastases from non-small cell lung
      cancer (NSCLC) is performed to identify patients who benefit from radiosurgery
      and to determine prognostic factors for survival. Eighty-six consecutive patients
      with a total of 110 brain metastases from NSCLC were treated with linac-based
      radiosurgery. Six patients with eight brain metastases who received radiosurgery
      as a focal boost to whole brain radiotherapy where excluded. Median age at
      treatment was 60 years. Median dose was 20 Gy/80%-isodose. A chi(2)-test was used
      to identify potential prognostic factors for local control of brain metastases
      and survival of the patients. Median follow-up was 6 months (range 1 1/2-77
      months) with 17/80 patients still alive. Median actuarial survival was
      significantly longer (P<0.004) in patients with metachronous onset of brain
      metastases in comparison to synchronous onset (8.3 vs. 3.3 months). Survival was
      significantly increased after radiosurgery in the absence of extracranial tumor
      progression (P<0.03). Eleven patients (14%) developed new brain metastases after
      radiosurgery after a latency of median 5 months. Actuarial local control rate was
      96% after 3 months. Local control was significantly increased with a prescribed
      dose > or=18 Gy/80%-isodose (P<0.01). We conclude that especially patients with
      poor prognostic factors and a limited number of brain metastases may be
      palliatively treated with radiosurgery alone. This approach allows to effectively
      control CNS manifestation of the disease and can be integrated into
      chemotherapeutic protocols.

PMID- 12057874
TI  - Highlights from the 7th central European lung cancer conference.

PMID- 12057873
TI  - Impact of COPD on pulmonary complications and on long-term survival of patients
      undergoing surgery for NSCLC.
AB  - PURPOSE: The purpose of our study was to determine the incidence of various types
      of postoperative pulmonary complications and to evaluate the impact of chronic
      obstructive pulmonary disease (COPD) on the long-term survival of patients with
      non-small cell lung cancer (NSCLC) undergoing pulmonary resection. METHODS: We
      performed a retrospective chart review of 244 patients who had undergone lung
      resection for NSCLC at Indiana University. COPD, defined as predicted forced
      expiratory volume in 1 s (FEV1)< or =70% and FEV1/FVC< or =70%, was determined
      based on preoperative pulmonary function testing in 78 of 244 patients (COPD
      group). The remaining 166 patients were classified as non-COPD. The incidence of
      postoperative complications, which included air leak of > or=10 days,
      atelectasis, pneumothorax, pneumonia, bronchopleural fistula, empyema, acute
      respiratory distress syndrome, mechanical ventilation of > or =7 days, and
      outpatient oxygen supplementation were compared between the two groups. Long-term
      survival and mortality due to respiratory failure were analyzed between the two
      groups using the Kaplan-Meier method and log rank test. RESULTS: All of the above
      stated postoperative pulmonary complications occurred more frequently in the COPD
      than in the non-COPD patients (all P<0.01). The overall 5-year survival rate was
      36.2% in the COPD and 41.2% in the non-COPD patients (P=0.1023). Five-year cancer
      related survival was 43.2% in the COPD and 47.7% in the non-COPD patients
      (P=0.357). There was no significant difference in survival among patients with
      different stages of lung cancer. However, the intercurrent survival, which is
      associated with non-cancer related death, was 60.1% in patients with COPD and
      86.2% in patients without COPD at 5 years (P<0.0001). The major cause of non
      cancer related death in the COPD group was respiratory failure (P=0.0008).
      CONCLUSION: The presence of COPD is an acceptable predictor of postoperative
      pulmonary complications in patients with NSCLC. COPD is also a significant risk
      factor for development of respiratory-related complications, which may explain
      the poor long-term survival in these patients.

PMID- 12057875
TI  - International conference on 'Non Small Cell Lung Cancer: Standards and New Trends
      in Diagnosis and Therapy', October 5-7, 2001, medical academy of Bialystok,
      Bialystok, Poland.

PMID- 12057876
TI  - Principles, organization, and operation of a DNA bank for clinical trials: a
      Department of Veterans Affairs cooperative study.
AB  - The mapping and sequencing of the human genome promises rapid growth in
      understanding the genetically influenced mechanisms that underlie human disease.
      To realize this promise fully, it is necessary to relate genetic information to
      clinical phenotypes. Genetic tissue banking in clinical studies provides
      opportunities to analyze the genetic contribution to variation in response to
      treatments. The challenges to progress are likely to come from the complex
      organizational, social, political, and ethical issues that must be resolved in
      order to put clinical and DNA bank information together. Concerns about subjects'
      rights, informed consent, privacy, and ownership of genetic material require
      attention in the development of DNA banks. In this paper we describe one approach
      to the solution of these problems that was adopted by one clinical trials group,
      the Department of Veterans Affairs Cooperative Studies Program.

PMID- 12057877
TI  - The bivariate continual reassessment method. extending the CRM to phase I trials
      of two competing outcomes.
AB  - Traditional phase I studies find the therapeutic dose of an investigational drug
      based solely on toxicity and without regard to the drug's efficacy. We propose
      extending the continual reassessment method (CRM) to a bivariate trial design in
      which the maximum tolerated dose is based jointly on both toxicity and disease
      progression. We call our study design bCRM, for bivariate CRM, which we apply to
      a study of bone marrow patients seeking to find the optimal time after bone
      marrow transplant at which to taper immune suppression and eventually begin donor
      leukocyte infusions. We demonstrate through simulation that bCRM has excellent
      operating characteristics and compare the performance of bCRM in a bone marrow
      transplantation study to designs proposed by previous investigators. We also
      attempt to provide some direction to future investigators with regard to
      plausible models and distributions to use with a bivariate study design.

PMID- 12057878
TI  - Guidelines for the design of clinical trials with longitudinal outcomes.
AB  - A common objective of longitudinal clinical trials is to compare rates of change
      in a continuous response variable between two groups. The power realized for such
      a study is a function of both the number of people recruited and the planned
      number of measurements for each participant. By varying these two quantities in
      opposite directions, power can be kept at the desired level. We consider the
      problem of how best to choose the sample size and frequency of measurement, with
      a view to minimizing either the total number of measurements or the cost of a
      study. Some general guidelines are first developed for the situation in which all
      participants have complete observations. In practice, however, longitudinal
      studies often suffer from dropout, where a participant leaves the study
      permanently so that no further observations are possible. We therefore consider
      the impact of unanticipated dropout on power and also ways of allowing for
      dropout at the design stage. Based on our results, we propose some general design
      guidelines for longitudinal trials comparing rates of change when dropout is
      present.

PMID- 12057879
TI  - Prospective preference assessment: a method to enhance the ethics and efficiency
      of randomized controlled trials.
AB  - The concomitant problems of underenrollment and selective enrollment limit the
      efficiency of many randomized controlled trials (RCTs). In addition, the
      traditional informed consent process is often inadequate to respect research
      participants' autonomy. Past efforts to overcome these problems are not
      universally applicable. A new method, called prospective preference assessment
      (PPA), is suggested as a way to simultaneously enhance participant accrual,
      identify groups of patients to whom a trial's results may apply, and promote
      participants' interests. PPA is a method by which investigators would evaluate
      potential trial participants' motivations for and concerns about enrolling in a
      planned trial prior to formal recruitment. The information provided by PPA would
      then be used to (1) modify the final trial design and conduct to make enrollment
      more attractive, and (2) identify ways in which the patients who do enroll may
      differ from those who do not, thereby elucidating the trial's generalizability.
      The methodologic and ethical advantages of this method are described, and
      potential barriers to the method's implementation are addressed. The added costs
      of prospectively assessing the views of potential research participants prior to
      initiating RCTs are considered in relation to the method's ability to enhance the
      value of the information to be obtained. It is concluded that PPA is a feasible
      approach to a more democratic and efficient research process and that its
      adoption would be consistent with current trends in health care.

PMID- 12057880
TI  - Recruitment of Hispanic women to the Women's Health Initiative. the case of
      Embajadoras in Arizona.
AB  - This study examined the use of lay advocates (i.e., women enrolled in a study who
      advocate to others) to improve recruitment among Hispanic women in the Arizona
      recruitment sites for a large-scale, national prevention study, the Women's
      Health Initiative (WHI). We examined whether trained, Hispanic lay advocates
      (called Embajadoras) brought more women into the study than a matched group of
      Hispanic and Anglo enrollees in the WHI who were supplied with brochures. Fifty
      six Hispanic participants in the WHI were randomized to receive training or no
      training on advocacy, and continued to meet quarterly for 18 months. Also, 42
      Anglo women were assigned to control. All groups received brochures to use for
      advocating the WHI. The number of women referred and enrolled was tracked as well
      as other factors expected to influence outcomes. Embajadoras were more successful
      at referral and enrollment than untrained Hispanic women and more successful at
      enrollment than untrained Anglo controls. Embajadoras were also found to
      distribute significantly more brochures than control groups. Therefore, a
      culturally aligned training program to encourage current Hispanic participants in
      a clinical trial to advocate the study to others may be an effective way to boost
      referrals and enrollments. Other potential influences on enrollment or referral
      success could not be determined due to the small sample size. Further study is
      needed to examine the best methods to encourage enrollment for women referred to
      the study.

PMID- 12057882
TI  - Issues in design and analysis of a randomized clinical trial to assess the safety
      of dental amalgam restorations in children.
AB  - The Casa Pia Study of the Health Effects of Dental Amalgams in Children is a
      randomized clinical trial designed to assess the safety of low-level mercury
      exposure from dental amalgam restorations in children. It is being carried out in
      507 students (8 to 12 years of age at enrollment) of the Casa Pia school system
      in Lisbon, Portugal, by an interdisciplinary collaborative research team from the
      University of Washington (Seattle) and the University of Lisbon, with funding
      from the National Institute of Dental and Craniofacial Research. Since the goal
      of the trial is to assess the safety of a treatment currently in use, rather than
      the efficacy of an experimental treatment, unique design issues come into play.
      The requirements to identify as participants children who have extensive unmet
      dental treatment needs and who can be followed for 7 years after initial
      treatment are somewhat in conflict, since those with the most treatment needs are
      usually in lower socioeconomic categories and more difficult to track. The
      identification of a primary study outcome measure around which to design the
      trial is problematic, since there is little evidence to indicate how health
      effects from such low-level exposure would be manifested. The solution involves
      the use of multiple outcomes. Since there are concerns about safety, multiple
      interim comparisons over time between treatment groups are called for which, in
      conjunction with the use of multiple outcomes, require an extension of
      statistical methodology to meet this requirement. Ethical questions that have to
      be addressed include whether assent of the children participating is required or
      appropriate, and whether the director of the school system, who is the legal
      guardian for approximately 20% of the students who are wards of the state and
      live in school residences, should provide consent for such a large number of
      children. Approaches taken to address these and other design issues are
      described.

PMID- 12057883
TI  - A placebo-controlled randomized trial of eradication of Helicobacter pylori in
      the general population: study design and response rates of the Bristol
      Helicobacter Project.
AB  - The Bristol Helicobacter Project is an ongoing, pragmatic, double-blind placebo
      controlled trial of the effect of Helicobacter pylori eradication on symptoms of
      dyspepsia, health utilization and costs, and quality of life in the adult
      population. Commencing in 1996, 27,536 individuals ages 20-59 years who were
      registered with seven primary care centers in Bristol and the surrounding areas
      in southwest England were invited to undergo a 13C urea breath test. There was no
      selection on the basis of symptoms and 23.5% had dyspepsia on entry to the study.
      A total of 10,537 people were tested (38.3% of those invited), 1636 tested
      positive (15.5% of those tested), and 1558 (95.2% of those who tested positive)
      were randomized to H. pylori eradication therapy or placebo. The rate of
      participation in the screening phase increased with age (odds ratio [OR]: 1.42
      per decade, 95% CI: 1.31 to 1.54) and female gender (OR: 1.35, 95% CI: 1.27 to
      1.43) but decreased with lower socioeconomic status (OR: 0.70, 95% CI: 0.56 to
      0.86 comparing lowest with highest category). H. pylori prevalence increased with
      age (OR: 1.69 per decade, 95% CI: 1.51 to 1.89) and lower socioeconomic status
      (OR: 1.33, 95% CI: 1.05 to 1.69) but was lower in women (OR: 0.87, 95% CI: 0.76
      to 1.00). Population-based trials of H. pylori eradication are feasible but
      necessitate screening large numbers of people to identify those who are infected
      and who may benefit from eradication. In the Bristol Helicobacter Project the
      rate of participation varied inversely with both social deprivation and the
      prevalence of the infection.

PMID- 12057884
TI  - The antibiotic treatment trial of Gulf War Veterans' Illnesses: issues, design,
      screening, and baseline characteristics.
AB  - Many veterans who were deployed to the Persian Gulf during the 1990-1991 Gulf War
      developed multiple unexplained symptoms such as pain, fatigue, and neurocognitive
      problems. This constellation of symptoms has been termed Gulf War Veterans'
      Illnesses (GWVI). Although there is no proven explanation for the cause of GWVI,
      one fairly widespread explanation is systemic Mycoplasma fermentans infection.
      The Antibiotic Treatment Trial of GWVI is a randomized placebo-controlled trial
      to determine whether a 1-year course of doxycycline treatment in deployed Gulf
      War veterans with GWVI and testing as Mycoplasma species positive will improve
      their overall functional status as measured by the Physical Component Summary of
      the SF-36V questionnaire. The study of a multisymptom illness such as GWVI is
      complicated by the nonspecific nature of the illness, the unknown etiology, and
      the lack of a widely accepted outcome measure. The presumption of mycoplasma
      infection raises concerns regarding the methodology for determination of
      mycoplasma infection, the choice of treatment, and the duration of treatment.
      However, such a presumption allows the formulation of a clear testable hypothesis
      that can be tested with treatments with known rates of adverse events and known
      activity against Mycoplasma species. This paper describes the major issues faced
      by the investigators during planning, the study design, the patient screening
      results, and the baseline characteristics of the study patients. There were 2712
      patients screened for study entry at 26 Department of Veterans Affairs and two
      Department of Defense medical centers. Of these, 491 met all study entry criteria
      and were randomized to either 1 year of doxycycline (200 mg/day) or 1 year of
      placebo. All patients were seen monthly during treatment and at 6 months after
      the end of treatment. Study patients had a mean age of 41 years and were mostly
      male (86%), white (64%), married (68%), and employed full-time (71%).

PMID- 12057885
TI  - Variability and Determinism in Motor Behavior
AB  - In investigations into perception-action systems, variability of observable
      behavior may be considered to (a) interfere with inquiry, (b) be neither
      detrimental nor particularly useful to inquiry, or (c) play a crucial role in
      inquiry. The authors underscore recent suggestions that alternative (c) is a
      preferred strategy for the study of many motor behaviors. In tutorial fashion,
      the authors review the concepts of variability and determinism with respect to
      postural and rhythmic movements. Study of the variability of those behaviors has
      revealed crucial features suggestive of underlying mechanisms and control, such
      as particular blends of noise and determinism (piecewise determinism). It has
      also revealed general lessons (for example, more variable does not mean more
      random and more controllable does not mean more deterministic) that may extend to
      other classes of perceptual behavior.

PMID- 12057886
TI  - Strategic calibration and spatial alignment: a model from prism adaptation.
AB  - Two types of adaptive processes involved in prism adaptation have been
      identified&colon: Slower spatial realignment among the several unique
      sensorimotor coordinate systems (spatial maps) and faster strategic motor control
      responses(including skill learning and calibration) to spatial misalignment. One
      measures the 1st process by assessing the aftereffects of prism exposure, whereas
      direct effects of the prism during exposure are a measure of the 2nd process. A
      model is described that relates those adaptive processes and distinguishes
      between extraordinary alignment and ordinary calibration. A conformal translation
      algorithm that operates on the hypothesized circuitry is proposed. The authors
      apply to the model to explain the advantage of visual calibration when the limb
      is seen in the starting position prior to movement initiation. Implications of
      the model for the use of prism adaptation as a tool for investigation of motor
      control and learning are discussed.

PMID- 12057887
TI  - Organization of drinking: postural characteristics of arm-head coordination.
AB  - Postural characteristics of components of a natural movement-taking a sip from a
      mug filled with water-were studied. The authors hypothesized that important
      postural characteristics of each of the components involved in natural drinking
      can be described with a single or a few significant parameters. Seated
      participants (N = 7) took a small sip from a mug (selected from a set of 4)
      placed in front of them on the table. Movement components selected for analysis
      were transporting the mug, tilting the mug, moving and tilting the head, and
      opening the mouth. The ratio of mug diameter to the distance from the level of
      water to the rim of the mug was introduced as an index of difficulty (ID). ID
      showed significant logarithmic relationships to a number of parameters that
      described different components of the movement, including movement time (MT).
      Significant logarithmic relationships between ID and MT were observed during
      movements performed under visual control and with eyes closed. The authors
      tentatively suggest that those relationships are consequences of Fitts' law and
      that Fitts' law be expanded to tasks that are characterized by permissible error
      margin, not necessarily related to the size of a spatial target, and that are not
      constrained by the typical instruction "as fast and accurate as possible". A
      possible interpretation of the present observations is that the task constraints
      imposed on a number of movement parameters during the task of drinking can be
      described with a single parameter.

PMID- 12057888
TI  - Lateral asymmetries in the development of the overarm throw.
AB  - Lateral asymmetries of manual, pedal, and ocular preferences, and motor asymmetry
      in the performance of the forceful overarm throw were analyzed in 71 children
      aged 4 to 10 years old. Performance with each side of the body was assessed on
      the basis of qualitative analysis, as proposed by M. A. Roberton and L. Halverson
      (1984) for identification of developmental stages by components of the task.
      Lateral preference was indicated by the frequency the children used the right or
      the left side of their body to carry out different manual, pedal, and ocular
      tasks. The overarm throw movement pattern was developed with both sides of the
      body but at different levels. Development of the nondominant side lagged behind
      that of the dominant side at all ages; a significant asymmetry in performance
      detected in the 4-year-olds was stable up to the age of 10 years. Indices of
      asymmetry for lateral preference and performance were found to be specific
      because no consistent correlations were observed among them throughout the age
      periods studied. Those results show the multidimensional character of human
      laterality and imply a property of motor development that prevents asymmetry of
      performance from increasing because of unilateral practice.

PMID- 12057889
TI  - Perceptual-motor contributions to static and dynamic balance control in children.
AB  - The authors addressed balance control in children from the perspective of skill
      development and examined the relationship between specific perceptual and motor
      skills and static and dynamic balance performance. Fifty 11- to 13-year-old
      children performed a series of 1-legged balance tasks while standing on a force
      platform. Postural control was reflected in the maximum displacement of the
      center of mass in anterior-posterior and mediolateral directions. Simple visual,
      discrimination, and choice reaction times; sustained attention; visuomotor
      coordination; kinesthesis; and depth perception were also assessed in a series of
      perceptual and motor tests. The correlation analysis revealed that balancing
      under static conditions was strongly associated with the ability to perceive and
      process visual information, which is important for feedback-based control of
      balance. On the other hand, when greater task demands were imposed on the system
      under dynamic balancing conditions, the ability to respond to the destabilizing
      hip abductions-adductions in order to maintain equilibrium was associated with
      motor response speed, suggesting the use of a descending, feedforward control
      strategy. Therefore, like adults, 11- to 13-year-old children have the ability to
      select varying balance strategies (feedback, feedforward, or both), depending on
      the constraints of a particular task.

PMID- 12057890
TI  - Enhancing the learning of sport skills through external-focus feedback.
AB  - The authors examined how the effectiveness of feedback for the learning of
      complex motor skills is affected by the focus of attention it induces. The
      feedback referred specifically either to body movements (internal focus) or to
      movement effects (external focus). In Experiment 1, groups of novices and
      advanced volleyball players (N = 48) practiced "tennis" serves under internal
      focus or external-focus feedback conditions in a 2 (expertise) x 2 (feedback
      type) design. Type of feedback did not differentially affect movement quality,
      but external-focus feedback resulted in greater accuracy of the serves than
      internal-focus feedback during both practice and retention, independent of the
      level of expertise. In Experiment 2, the effects of relative feedback frequency
      as a function of attentional focus were examined. A 2 (feedback frequency: 100%
      vs. 33%) x 2 (feedback type) design was used. Experienced soccer players (N = 52)
      were required to shoot lofted passes at a target. External-focus feedback
      resulted in greater accuracy than internal-focus feedback did. In addition,
      reduced feedback frequency was beneficial under internal-focus feedback
      conditions, whereas 100% and 33% feedback were equally effective under external
      focus conditions. The results demonstrate the effectiveness of effect-related, as
      opposed to movement-related, feedback and also suggest that there is a need to
      revise current views regarding the role of feedback for motor learning.

PMID- 12057891
TI  - Generation of bimanual trajectories of disparate eccentricity: levels of
      interference and spontaneous changes over practice.
AB  - The authors examined intermanual interactions of 2 hands that were required to
      concurrently follow trajectories that differed in eccentricity. Ten healthy
      participants attempted to learn to trace 2 figures, a circle and an ellipse, with
      bilaterally isochronous (1:1) timing demands. Initial unimanual trials were
      followed by bilateral practice comprising 750 movement cycles. Two objectives
      were addressed: The authors' primary aim was to determine if kinematic interlimb
      interference is evident independent of spatial and temporal interference and to
      observe the potential practice-related changes in the nature of that
      interference. That test was afforded by participants' natural tendency to draw a
      circle with a relatively constant tangential velocity and an ellipse with a
      systematically varying velocity. A second aim was to observe the nature of
      spontaneous changes in the performance of each individual effector, and in the
      relationship between effectors, across practice. Those objectives were
      specifically addressed in a context in which augmented feedback was not available
      to direct the learners' attention to a particular feature of performance. The
      results suggested that interlimb assimilation of spatial features is the primary
      source of interference for that task and that apparent effects at the kinematic
      level are the secondary, indirect product of spatial coupling. Those results were
      found across blocks of practice. With respect to nondirected performance changes,
      substantially less improvement was evident in the performance of each individual
      effector than in the reduction of interlimb interference. Specifically, no
      practice-related changes in temporal variability or velocity bias, and minimal
      changes in trajectory smoothness, were evident in individual limbs. Conversely,
      significant reductions were observed in the variability of relative phase between
      limbs and in the magnitude of interlimb phase lag.

PMID- 12057892
TI  - Quiet eye duration, expertise, and task complexity in near and far aiming tasks.
AB  - . Skilled (n = 12) and less skilled (n = 12) billiards players participated in 2
      experiments in which the relationship between quiet eye duration, expertise, and
      task complexity was examined in a near and a far aiming task. Quiet eye was
      defined as the final fixation on the target prior to the initiation of movement.
      In Experiment 1, skilled performers exhibited longer fixations on the target
      (quiet eye) during the preparation phase of the action than their less skilled
      counterparts did. Quiet eye duration increased as a function of shot difficulty
      and was proportionally longer on successful than on unsuccessful shots for both
      groups of participants. In Experiment 2, participants executed shots under 3
      different time-constrained conditions in which quiet eye periods were
      experimentally manipulated. Shorter quiet eye periods resulted in poorer
      performance, irrespective of participant skill level. The authors argue that
      quiet eye duration represents a critical period for movement programming in the
      aiming response.

PMID- 12057894
TI  - In memorium G. Jeanette Thorbecke, 1929-2001.

PMID- 12057896
TI  - New paradigm for vessel intravasation by tumor cells.

PMID- 12057895
TI  - Proprotein convertases in tumor progression and malignancy: novel targets in
      cancer therapy.
AB  - The mammalian subtilisin/kexin-like proprotein convertase (PC) family has been
      implicated in the activation of a wide spectrum of proteins. These proteins are
      usually synthesized as inactive precursors before their conversion to fully
      mature bioactive forms. A large majority of these active proteins such as matrix
      metalloproteases, growth factors, and adhesion molecules are crucial in the
      processes of cellular transformation, acquisition of the tumorigenic phenotype,
      and metastases formation. Inhibition of PCs significantly affects the malignant
      phenotype of various tumor cells. In addition to direct tumor cell proliferation
      and migration blockade, PC inhibitors can also be used to target tumor
      angiogenesis. In this Review article we discuss a number of recent findings on
      the clinical relevance of PCs in cancer patients, their implication in the
      regulation of multiple cellular functions that impact on the invasive/metastatic
      potential of cancer cells. Thus, PC inhibitors may constitute new promising
      agents for the treatment of multiple tumors and/or in adjuvant therapy to prevent
      recurrence.

PMID- 12057897
TI  - Molecular rearrangements and morphology in thyroid cancer.

PMID- 12057898
TI  - Down-regulation of GATA-3 expression during human papillomavirus-mediated
      immortalization and cervical carcinogenesis.
AB  - To identify cellular genes that may be involved in human papillomavirus (HPV)
      mediated immortalization mRNA differential display analysis was performed on
      preimmortal and subsequent immortal stages of four human keratinocyte cell lines
      transformed by HPV type 16 or 18 DNA. This yielded a cDNA fragment encoding the
      transcription factor GATA-3 that was strongly reduced in intensity in all
      immortal stages of the four cell lines. A marked reduction in both GATA-3 mRNA
      and protein expression in HPV-immortalized cell lines was confirmed by reverse
      transcriptase-polymerase chain reaction, Western blot analysis, and
      immunohistochemistry and was also shown to be apparent in cervical carcinoma cell
      lines. Immunohistochemical analysis of cervical tissue specimens showed a clear
      nuclear staining for GATA-3 in normal cervical squamous epithelium (n = 14) and
      all cervical intraepithelial neoplasia (CIN) I (n = 6) and CIN II lesions (n =
      2). In contrast, 11% (1 of 9) of CIN III lesions and 67% (8 of 12) of cervical
      squamous cell carcinomas revealed a complete absence of GATA-3 immunostaining.
      Hence, complete down-regulation of GATA-3 expression represents a rather late
      event during cervical carcinogenesis. Whether GATA-3 down-regulation is
      etiologically involved in HPV-mediated immortalization and cervical
      carcinogenesis remains to be examined.

PMID- 12057899
TI  - Endometrial and colorectal tumors from patients with hereditary nonpolyposis
      colon cancer display different patterns of microsatellite instability.
AB  - The colorectum and uterine endometrium are the two most commonly affected organs
      in hereditary nonpolyposis colon cancer (HNPCC), but the genetic basis of organ
      selection is poorly understood. As tumorigenesis in HNPCC is driven by deficient
      DNA mismatch repair (MMR), we compared its typical consequence, instability at
      microsatellite sequences, in colorectal and endometrial cancers from patients
      with identical predisposing mutations in the MMR genes MLH1 or MSH2. Analysis of
      non-coding (BAT25, BAT26, and BAT40) and coding mononucleotide repeats (MSH6,
      MSH3, MLH3, BAX, IGF2R, TGF beta RII, and PTEN), as well as MLH1- and MSH2-linked
      dinucleotide repeats (D3S1611 and CA7) revealed significant differences, both
      quantitative and qualitative, between the two tumor types. Whereas colorectal
      cancers displayed a predominant pattern consisting of instability at the BAT loci
      (in 89% of tumors), TGF beta RII (73%), dinucleotide repeats (70%), MSH3 (43%),
      and BAX (30%), no such single pattern was discernible in endometrial cancers.
      Instead, the pattern was more heterogeneous and involved a lower proportion of
      unstable markers per tumor (mean 0.27 for endometrial cancers versus 0.45 for
      colorectal cancers, P < 0.001) and shorter allelic shifts for BAT markers
      (average 5.1 bp for unstable endometrial cancers versus 9.3 bp for colorectal
      cancers, P < 0.001). Among the individual putative "target" loci, PTEN
      instability was associated with endometrial cancers and TGF beta RII instability
      with colon cancers. The different instability profiles in endometrial and
      colorectal cancers despite identical genetic predisposition underlines organ
      specific differences that may be important determinants of the HNPCC tumor
      spectrum.

PMID- 12057901
TI  - A new method to extract nuclei from paraffin-embedded tissue to study lymphomas
      using interphase fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization (FISH) is difficult to accomplish using thin
      sections of paraffin-embedded lymphoid tissue because of the high cellularity and
      truncated cells that interfere with accurate scoring of individual nuclei. We
      modified and tested a new technique to isolate individual nuclei from tissue
      cores of paraffin-embedded tissue processed with xylene, proteinase K, citric
      acid, and pepsin. The efficacy of this method to study paraffin-embedded tissue
      was investigated in six normal lymph nodes or tonsils and 32 malignant lymphomas
      including five mantle cell, five follicular, five Burkitt, five extranodal
      marginal zone lymphomas of mucosa-associated lymphoid tissue, five anaplastic
      large-cell, and seven diffuse large B-cell. Fusion of CCND1 and IgH, BCL2 and
      IgH, c-myc and IgH, and MALT1 and API2 were detected using probes with a dual
      fusion FISH strategy. Anomalies involving ALK and BCL6 were detected using break
      apart FISH probes. FISH studies were successful for each of the 38 specimens.
      Chromosome anomalies were detected in each malignant specimen, but not in the
      normal lymphoid tissue. The correct chromosome anomaly was detected in 22 of 22
      specimens with genetic abnormalities that were established by other genetic
      techniques. This FISH technique is useful to detect chromosome anomalies with
      high sensitivity and specificity in paraffin-embedded tissue and may provide
      important diagnostic and prognostic genetic information.

PMID- 12057900
TI  - Rapid visualization at high resolution of pathogens by atomic force microscopy:
      structural studies of herpes simplex virus-1.
AB  - A relatively crude preparation of herpes simplex virus was rapidly visualized by
      atomic force microscopy after exposure to conditions that produced gradual
      degradation of the virions. Images were obtained of 1) the intact, enveloped
      virus; 2) the underlying capsid with associated tegument proteins along with
      fragments of the membrane; 3) the capsomeres composing the capsid and their
      surface arrangement; 4) damaged and partially degraded capsids with missing
      capsomeres; and 5) the DNA extruded from damaged virions. These images provide a
      unique perspective on the structures of individual virus particles. Atomic force
      microscopy can thus be used as a diagnostic tool to provide a rapid way to obtain
      high-resolution images of human pathogens from crude preparations. It is a useful
      technique that complements X-ray-based structure determination, cryo-electron
      microscopy techniques, and optical microscopies in the field of molecular
      pathogenesis.

PMID- 12057902
TI  - An invasion-independent pathway of blood-borne metastasis: a new murine mammary
      tumor model.
AB  - It is generally believed that active invasion by cancer cells is essential to the
      metastatic process. In this report, we describe a murine mammary tumor (MCH66)
      model of metastasis that does not require invasion into the vascular wall of both
      the primary tumor and the target organ, in this case, the lung. The process
      involves intravasation of tumor nests surrounded by sinusoidal blood vessels,
      followed by intravascular tumor growth in the lung, without penetration of the
      vascular wall during the process. Comparative studies using a nonmetastatic MCH66
      clone (MCH66C8) and another highly invasive metastatic cell line (MCH416)
      suggested that high angiogenic activity and sinusoidal remodeling of tumor blood
      vessels were prerequisites for MCH66 metastasis. Differential cDNA analysis
      identified several genes that were overexpressed by MCH66, including genes for
      the angiogenesis factor pleiotrophin, and extracellular matrix-associated
      molecules that may modulate the microenvironment toward neovascularization. Our
      analyses suggest that tumor angiogenesis plays a role in the induction of
      invasion-independent metastasis. This model should prove useful in screening and
      development of new therapeutic agents for cancer metastasis.

PMID- 12057903
TI  - Altered calcium-mediated cell signaling in keratinocytes cultured from patients
      with neurofibromatosis type 1.
AB  - Capacitative calcium entry and calcium wave propagation were studied in
      keratinocytes cultured from control persons and patients with type 1
      neurofibromatosis. The cells were stimulated mechanically in the presence of
      inhibitors of gap-junctional or ATP-mediated communication to determine which
      pathways are operative in Ca(2+) signaling between these cells. Keratinocytes
      cultured from patients with type 1 neurofibromatosis (NF1) had a tendency to form
      cultures with markedly altered calcium-related signaling characteristics.
      Specifically, the resting Ca(2+) levels, intracellular Ca(2+) stores,
      capacitative calcium influx, and gap-junctional signal transduction were
      defective in NF1 keratinocytes. Western transfer analysis revealed apparently
      equal connexin 43 protein levels in normal control and in NF1 keratinocytes.
      Indirect immunofluorescence, however, demonstrated that connexin 43 was
      relatively evenly distributed in NF1 cells and did not form typical gap
      junctional plaques between keratinocytes. Furthermore, the speed of the calcium
      wave was reduced in NF1 cells compared to normal keratinocytes. The results
      demonstrate that keratinocytes cultured from patients with NF1 display altered
      calcium-mediated signaling between cells.

PMID- 12057904
TI  - Increased localization and substrate activation of protein kinase C delta in lung
      epithelial cells following exposure to asbestos.
AB  - The protein kinase C (PKC) family consists of several isozymes whose substrates
      may be necessary for the regulation of key cellular events important in the
      pathogenesis of proliferative diseases. Asbestos is a carcinogen and
      fibroproliferative agent in lung that may cause cell signaling events through
      activation of PKC. Here we used a murine inhalation model of asbestos-induced
      inflammation and fibrosis to examine immunoreactivity of PKC delta and its
      substrate, phosphorylated-adducin (p-adducin), in cells of the lung. Moreover, we
      characterized PKC delta and p-adducin expression in a pulmonary epithelial cell
      line (C10) in both log versus confluent cells and in cells after mechanical
      wounding or crocidolite asbestos exposure. Both PKC delta and p-adducin were
      almost exclusively expressed in bronchiolar and alveolar type II (ATII)
      epithelial cells in lung sections and increased in these cell types after
      inhalation of asbestos by mice. Increases in membrane and nuclear localization of
      PKC delta were seen in log phase as compared to confluent C10 cells. Moreover,
      enhanced immunoreactivity of PKC delta was observed in epithelial cells
      expressing proliferating cell nuclear antigen (PCNA) after mechanical wounding or
      exposure to asbestos fibers. These studies show that activated PKC delta in
      pulmonary epithelial cells is a consequence of inhalation of asbestos and may be
      linked to the activation of cell proliferation.

PMID- 12057905
TI  - Renal fibrosis. Extracellular matrix microenvironment regulates migratory
      behavior of activated tubular epithelial cells.
AB  - During progression of chronic renal disease, qualitative and quantitative changes
      in the composition of tubular basement membranes (TBMs) and interstitial matrix
      occur. Transforming growth factor (TGF)-beta(1)-mediated activation of tubular
      epithelial cells (TECs) is speculated to be a key contributor to the progression
      of tubulointerstitial fibrosis. To further understand the pathogenesis associated
      with renal fibrosis, we developed an in vitro Boyden chamber system using renal
      basement membranes that partially mimics in vivo conditions of TECs during health
      and disease. Direct stimulation of TECs with TGF-beta(1)/epithelial growth factor
      results in an increased migratory capacity across bovine TBM preparations. This
      is associated with increased matrix metalloproteinase (MMP) production, namely
      MMP-2 and MMP-9. Indirect chemotactic stimulation by TGF-beta(1)/EGF or collagen
      type I was insufficient in inducing migration of untreated TECs across bovine TBM
      preparation, suggesting that basement membrane integrity and composition play an
      important role in protecting TECs from interstitial fibrotic stimuli.
      Additionally, neutralization of MMPs by COL-3 inhibitor dramatically decreases
      the capacity of TGF-beta(1)-stimulated TECs to migrate through bovine TBM
      preparation. Collectively, these results demonstrate that basement membrane
      structure, integrity, and composition play an important role in determining
      interstitial influences on TECs and subsequent impact on potential aberrant cell
      matrix interactions.

PMID- 12057906
TI  - Adenosine promotes wound healing and mediates angiogenesis in response to tissue
      injury via occupancy of A(2A) receptors.
AB  - Recent evidence indicates that topical application of adenosine A(2A) receptor
      agonists, unlike growth factors, increases the rate at which wounds close in
      normal animals and promotes wound healing in diabetic animals as well as growth
      factors, yet neither the specific adenosine receptor involved nor the
      mechanism(s) by which adenosine receptor occupancy promotes wound healing have
      been fully established. To determine which adenosine receptor is involved and
      whether adenosine receptor-mediated stimulation of angiogenesis plays a role in
      promotion of wound closure we compared the effect of topical application of the
      adenosine receptor agonist CGS-21680 (2-p-[2-carboxyethyl]phenethyl-amino-5'-N
      ethylcarboxamido-adenosine) on wound closure and angiogenesis in adenosine A(2A)
      receptor knockout mice and their wild-type littermates. There was no change in
      the rate of wound closure in the A(2A) receptor knockout mice compared to their
      wild-type littermates although granulation tissue formation was nonhomogeneous
      and there seemed to be greater inflammation at the base of the wound. Topical
      application of CGS-21680 increased the rate of wound closure and increased the
      number of microvessels in the wounds of wild-type mice but did not affect the
      rate of wound closure in A(2A) receptor knockout mice. Similarly, in a model of
      internal trauma and repair (murine air pouch model), endogenously produced
      adenosine released into areas of internal tissue injury stimulates angiogenesis
      because there was a marked reduction in blood vessels in the walls of healing air
      pouches of A(2A) receptor knockout mice compared to their wild-type controls.
      Inflammatory vascular leakage and leukocyte accumulation in the inflamed air
      pouch were similarly reduced in the A(2A) receptor knockout mice reflecting the
      reduced vascularity. Thus, targeting the adenosine A(2A) receptor is a novel
      approach to promoting wound healing and angiogenesis in normal individuals and
      those suffering from chronic wounds.

PMID- 12057908
TI  - Global gene expression profiling of end-stage dilated cardiomyopathy using a
      human cardiovascular-based cDNA microarray.
AB  - To obtain a genomic portrait of heart failure derived from end-stage dilated
      cardiomyopathy (DCM), we explored expression analysis using the CardioChip, a
      nonredundant 10,848-element human cardiovascular-based expressed sequence tag
      glass slide cDNA microarray constructed in-house. RNA was extracted from the left
      ventricular free wall of seven patients undergoing transplantation, and five
      nonfailing heart samples. Cy3- and Cy5-labeled (and reverse dye-labeled) cDNA
      probes were synthesized from individual diseased or nonfailing adult heart RNA,
      and hybridized to the array. More than 100 transcripts were consistently
      differentially expressed in DCM >1.5-fold (versus pooled nonfailing heart, P <
      0.05). Atrial natriuretic peptide was found to be up-regulated in DCM (19-fold
      compared to nonfailing, P < 0.05), as well as numerous sarcomeric and
      cytoskeletal proteins (eg, cardiac troponin, tropomyosin), stress response
      proteins (eg, HSP 40, HSP 70), and transcription/translation regulators (eg,
      CCAAT box binding factor, eIF-1AY). Down-regulation was most prominently observed
      with cell-signaling channels and mediators, particularly those involved in Ca(2+)
      pathways (Ca(2+)/calmodulin-dependent kinase, inositol 1,4,5-trisphosphate
      receptor, SERCA). Most intriguing was the co-expression of several novel, cardiac
      enriched expressed sequence tags. Quantitative real-time reverse transcriptase
      polymerase chain reaction of a selection of these clones verified expression. Our
      study provides a preliminary molecular profile of DCM using the largest human
      heart-specific cDNA microarray to date.

PMID- 12057907
TI  - Linking hematopoiesis to endochondral skeletogenesis through analysis of mice
      transgenic for collagen X.
AB  - Each skeletal element where marrow develops is first defined by a hypertrophic
      cartilage blueprint. Through programmed tissue substitution, the cartilaginous
      skeletal model is replaced by trabecular bone and marrow, with accompanying
      longitudinal tissue growth. During this process of endochondral ossification,
      hypertrophic cartilage expresses a unique matrix molecule, collagen X. Previously
      we reported that transgenic mice with dominant interference collagen X mutations
      develop variable skeleto-hematopoietic abnormalities, manifested as growth plate
      compressions, diminished trabecular bone, and reduced lymphatic organs (Nature
      1993, 365:56). Here, histology and flow cytometry reveal marrow hypoplasia and
      impaired hematopoiesis in all collagen X transgenic mice. A subset of mice with
      perinatal lethality manifested the most severe skeletal defects and a reduction
      of marrow hematopoiesis, highlighted by a lymphocyte decrease. Thymic reduction
      is accompanied by a paucity of cortical immature T cells, consistent with the
      marrow's inability to replenish maturing cortical lymphocytes. Diminished spleens
      exhibit indistinct lymphatic nodules and red pulp depletion; the latter
      correlates with erythrocyte-filled vascular sinusoids in marrows. All mice
      display reduced B cells in marrows and spleens, and elevated splenic T cells.
      These hematopoietic defects underscore an unforeseen link between hypertrophic
      cartilage, endochondral ossification, and establishment of the marrow
      microenvironment required for blood cell differentiation.

PMID- 12057909
TI  - Signature tau neuropathology in gray and white matter of corticobasal
      degeneration.
AB  - Corticobasal degeneration (CBD) is an adult-onset progressive neurodegenerative
      disorder characterized by L-dopa-resistant rigidity, focal cortical deficits, and
      variable dementia. The neuropathological hallmark of CBD is the deposition of
      filamentous inclusions in neurons and glia composed of hyperphosphorylated tau
      with only four microtubule-binding repeats (4R-tau). To characterize the regional
      burden of tau pathology in CBD, we studied 12 brains with the neuropathological
      diagnosis of CBD using biochemical and histochemical techniques. Eleven brain
      regions were evaluated including gray and white matter from frontal, parietal,
      temporal, and occipital lobes and cerebellum as well as basal ganglia. Although
      the distribution of tau pathology was variable, neuropathological and biochemical
      data showed a similar burden of tau abnormalities in frontal, temporal, and
      parietal lobes and basal ganglia of both hemispheres. This included abundant,
      sarkosyl-insoluble 4R-tau in both gray and white matter of two or more of these
      cortical regions and basal ganglia, and to a lesser extent, cerebellar white
      matter. The insoluble tau pathology in gray and white matter showed overlapping
      but distinct phosphorylated epitopes suggesting cell-type and subcellular
      localization (ie, cell bodies versus cell processes)-specific differences in tau
      phosphorylation. In contrast, soluble tau was composed of normal 4R/3R-tau ratios
      indicating no gross abnormality in tau splicing. Thus, although clinically
      heterogeneous, CBD is a distinct lobar and basal ganglionic tauopathy with
      selective aggregation of 4R-tau.

PMID- 12057910
TI  - Mutation cluster region, association between germline and somatic mutations and
      genotype-phenotype correlation in upper gastrointestinal familial adenomatous
      polyposis.
AB  - Studies of adenomatous polyposis coli (APC) mutations in familial adenomatous
      polyposis (FAP) have focused on large bowel disease. It has been found that: 1)
      germline APC mutations around codon 1300 are associated with severe colorectal
      polyposis; 2) somatic APC mutations in colorectal tumors tend to cluster
      approximately between codons 1250 and 1450; and 3) patients with germline
      mutations close to codon 1300 tend to acquire somatic mutations (second hits) in
      their colorectal polyps by allelic loss, whereas the tumors of other FAP patients
      have truncating second hits. Using new and published data, we have investigated
      how germline and somatic APC mutations influence the pathogenesis of upper
      gastrointestinal polyps in FAP. We have compared the results with those from
      colorectal disease. We found that somatic mutations in upper gastrointestinal
      polyps cluster approximately between codons 1400 and 1580. Patients with germline
      APC mutations after codon 1400 tend to show allelic loss in their upper
      gastrointestinal polyps; the tumors of other patients have truncating somatic
      mutations after codon 1400. Finally, patients with germline mutations after codon
      1400 tend to have more severe duodenal polyposis (odds ratio, 5.72; 95%
      confidence interval, 1.13 to 28.89; P = 0.035). Thus, in both upper
      gastrointestinal and colorectal tumors, a specific region of the APC gene is
      associated with severe disease, clustering of somatic mutations, and loss of the
      wild-type allele. However, the region concerned is different in upper
      gastrointestinal and colorectal disease. The data suggest that loss of all APC
      SAMP repeats is probably necessary for duodenal and gastric tumorigenesis in FAP,
      as it is in colonic tumors. Compared with colonic tumors, however, retention of a
      greater number of beta-catenin binding/degradation repeats is optimal for
      tumorigenesis in upper gastrointestinal FAP.

PMID- 12057911
TI  - Deficiency of microvascular thrombomodulin and up-regulation of protease
      activated receptor-1 in irradiated rat intestine: possible link between
      endothelial dysfunction and chronic radiation fibrosis.
AB  - Microvascular injury is believed to be mechanistically involved in radiation
      fibrosis, but direct molecular links between endothelial dysfunction and
      radiation fibrosis have not been established in vivo. We examined radiation
      induced changes in endothelial thrombomodulin (TM) and protease-activated
      receptor-1 (PAR-1) in irradiated intestine, and their relationship to structural,
      cellular, and molecular aspects of radiation injury. Rat small intestine was
      locally exposed to fractionated X-radiation. Structural injury was assessed 24
      hours and 2, 6, and 26 weeks after the last radiation fraction using quantitative
      histology and morphometry. TM, neutrophils, transforming growth factor-beta, and
      collagens I and III were assessed by quantitative immunohistochemistry. PAR-1
      protein was localized immunohistochemically, and cells expressing TM or PAR-1
      transcript were identified by in situ hybridization. Steady-state PAR-1 mRNA
      levels in intestinal smooth muscle were determined using laser capture
      microdissection and competitive reverse transcriptase-polymerase chain reaction.
      Radiation caused a sustained, dose-dependent decrease in microvascular TM. The
      number of TM-positive vessels correlated with all parameters of radiation
      enteropathy and, after adjusting for radiation dose and observation time in a
      statistical model, remained independently associated with neutrophil
      infiltration, intestinal wall thickening, and collagen I accumulation. PAR-1
      immunoreactivity and transcript increased in vascular and intestinal smooth
      muscle cells in irradiated intestine. PAR-1 mRNA increased twofold in irradiated
      intestinal smooth muscle. Intestinal irradiation up-regulates PAR-1 and causes a
      dose-dependent, sustained deficiency of microvascular TM that is independently
      associated with the severity of radiation toxicity. Interventions aimed at
      preserving or restoring endothelial TM or blocking PAR-1 should be explored as
      strategies to increase the therapeutic ratio in clinical radiation therapy.

PMID- 12057912
TI  - Fragile histidine triad gene abnormalities in the pathogenesis of gallbladder
      carcinoma.
AB  - There is limited information about the molecular changes involved in the
      pathogenesis of gallbladder carcinoma (GBC). Our recent allelotyping analyses
      have indicated that chromosome 3p loss of heterozygosity (LOH), including the
      fragile histidine triad (FHIT) candidate tumor-suppressor gene locus at 3p14.2,
      is frequently detected in this neoplasm. To investigate the role of the FHIT
      abnormalities in the multistage sequential development of GBC, 33 formalin-fixed
      paraffin-embedded invasive GBC specimens and 76 accompanying histologically
      normal (n = 43) and dysplastic (n = 33) epithelia were examined by immunostaining
      for expression of Fhit protein. Allele loss at the FHIT gene locus (3p14.2) was
      studied in all GBCs and in a subset of accompanying gallbladder epithelia by
      polymerase chain reaction-based LOH analysis, using three 3p14.2 microsatellite
      markers. In addition, histologically normal epithelium from chronic cholecystitis
      (n = 19) and dysplasia (n = 13) from gallbladder specimens without cancer were
      examined for immunostaining and LOH. There was a progressive increase in both the
      frequency of loss of Fhit expression and LOH at FHIT with increasing severity of
      histopathological changes. FHIT abnormalities were occasionally demonstrated in
      histologically normal gallbladder epithelium. Dysplastic foci demonstrated
      frequent reduction or absence of Fhit immunostaining (38 to 55%) and FHIT allelic
      loss (33 to 46%). In invasive tumors, these abnormalities were even higher, with
      79% reduction or absence of Fhit immunostaining and 76% FHIT allele loss. A high
      correlation (70%) was observed between Fhit immunostaining abnormalities and
      allele loss in GBC specimens (P < 0.05). Although a high frequency of FHIT locus
      breakpoints were detected in both invasive and dysplastic gallbladder specimens,
      no intronic homozygous deletions on FHIT were detected in GBCs. FHIT gene
      abnormalities are nearly universal in GBC and these changes are detected early in
      the sequential development of this neoplasm. Our findings indicate that the FHIT
      gene is one of the chromosome 3p putative tumor suppressor genes involved in the
      pathogenesis of this highly malignant neoplasm.

PMID- 12057913
TI  - Latent transforming growth factor-beta activation in mammary gland: regulation by
      ovarian hormones affects ductal and alveolar proliferation.
AB  - Transforming growth factor-beta1 (TGF-beta 1) is a pluripotent cytokine that can
      inhibit epithelial proliferation and induce apoptosis, but is also widely
      implicated in breast cancer progression. Understanding its biological action in
      mammary development is critical for understanding its role in cancer. TGF-beta 1
      is produced as a latent complex that requires extracellular activation before
      receptor binding. To better understand the spatial and temporal regulation of its
      action during mammary gland development, we examined the pattern of activation in
      situ using antibodies selected to distinguish between latent and active TGF-beta.
      Activation was highly restricted. TGF-beta 1 activation was localized primarily
      to the epithelium, and within the epithelium it was restricted to luminal
      epithelial cells but absent from either cap or myoepithelial cells. Within the
      luminal epithelium, we noted a further restriction. During periods of
      proliferation (ie, puberty, estrus and pregnancy), which are stimulated by
      ovarian hormones, TGF-beta 1 activation decreased in some cells, consistent with
      preparation for proliferation. Paradoxically, other cells simultaneously increase
      TGF-beta 1 immunoreactivity, which suggests that TGF-beta 1 differentially
      restrains epithelial subpopulations from responding to hormonal signals to
      proliferate. These data suggest that endogenous TGF-beta 1 activation and thus
      activity are regulated by ovarian hormones. To determine the specific
      consequences of TGF-beta 1 activity, we manipulated TGF-beta 1 levels in vivo
      using Tgfbeta 1 knockout mice and undertook tissue recombination experiments with
      heterozygous tissue. In Tgfbeta 1 heterozygous mice, which have <10% wild-type
      levels of TGF-beta1, ductal development during puberty and alveolar development
      during pregnancy were accelerated, consistent with its role as a growth
      inhibitor. The proliferative index of Tgfbeta 1+/- epithelium was increased
      approximately twofold in quiescent tissue and fourfold in proliferating tissue
      but both ducts and alveoli were grossly and histologically normal. To test
      whether epithelial TGF-beta1 was critical to the proliferative phenotype, Tgfbeta
      1+/+ and +/- epithelium were transplanted into +/+ mammary stroma. The outgrowth
      of Tgfbeta 1+/- epithelium was accelerated in wild-type hosts, indicating that
      the phenotype was intrinsic to the epithelium. Moreover, proliferation was 15
      fold greater in Tgfbeta 1+/- than wild-type mice after ovariectomy and treatment
      with estrogen and progesterone, suggesting that TGF-beta 1 acts in an autocrine
      or juxtacrine manner to regulate epithelial proliferation. Together these data
      indicate that ovarian hormones regulate TGF-beta 1 activation, which in turn
      restricts proliferative response to hormone signaling.

PMID- 12057914
TI  - Gene expression profiling of mouse bladder inflammatory responses to LPS,
      substance P, and antigen-stimulation.
AB  - Inflammatory bladder disorders such as interstitial cystitis (IC) deserve
      attention since a major problem of the disease is diagnosis. IC affects millions
      of women and is characterized by severe pain, increased frequency of micturition,
      and chronic inflammation. Characterizing the molecular fingerprint (gene profile)
      of IC will help elucidate the mechanisms involved and suggest further approaches
      for therapeutic intervention. Therefore, in the present study we used established
      animal models of cystitis to determine the time course of bladder inflammatory
      responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P
      (SP) by morphological analysis and cDNA microarrays. The specific aim of the
      present study was to compare bladder inflammatory responses to antigen, LPS, and
      SP by morphological analysis and cDNA microarray profiling to determine whether
      bladder responses to inflammation elicit a specific universal gene expression
      response regardless of the stimulating agent. During acute bladder inflammation,
      there was a predominant infiltrate of polymorphonuclear neutrophils into the
      bladder. Time-course studies identified early, intermediate, and late genes that
      were commonly up-regulated by all three stimuli. These genes included:
      phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF,
      proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen
      R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription
      factors, and cytoskeleton and motility proteins. Another cluster indicated genes
      that were commonly down-regulated by all three stimuli and included HSF2, NF
      kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore,
      we determined gene profiles that identify the transition between acute and
      chronic inflammation. During chronic inflammation, the urinary bladder presented
      a predominance of monocyte/macrophage infiltrate and a concomitant increase in
      the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic
      receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene
      2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel,
      prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude
      that microarray analysis of genes expressed in the bladder during experimental
      inflammation may be predictive of outcome. Further characterization of the
      inflammation-induced gene expression profiles obtained here may identify novel
      biomarkers and shed light into the etiology of cystitis.

PMID- 12057915
TI  - The combination of ischemic preconditioning and liver Bcl-2 overexpression is a
      suitable strategy to prevent liver and lung damage after hepatic ischemia
      reperfusion.
AB  - The present study evaluates the effectiveness of ischemic preconditioning and Bcl
      2 overexpression against the liver and lung damage that follow hepatic ischemia
      reperfusion and investigates the underlying protective mechanisms.
      Preconditioning and Bcl-2, respectively, reduced the increased tumor necrosis
      factor (TNF) and macrophage inflammatory protein-2 (MIP)-2 levels observed after
      hepatic reperfusion. Bcl-2 overexpression or anti-MIP-2 pretreatment seems to be
      more effective than preconditioning or anti-TNF pretreatment against inflammatory
      response, microcirculatory disorders, and subsequent hepatic ischemia-reperfusion
      injury. Furthermore, each one of these strategies individually was unable to
      completely inhibit hepatic injury. The combination of preconditioning and Bcl-2
      overexpression as well as the combined anti-TNF and anti-MIP-2 pretreatment
      totally prevented hepatic injury, whereas the benefits of preconditioning and Bcl
      2 were abolished by TNF and MIP-2. In contrast to preconditioning, Bcl-2 did not
      modify lung damage induced by hepatic reperfusion. This could be explained by the
      differential effect of both treatments on TNF release. Anti-TNF therapy or
      preconditioning, by reducing TNF release, reduced pulmonary inflammatory
      response, whereas the benefits of preconditioning on lung damage were abolished
      by TNF. Thus, the induction of both Bcl-2 overexpression in liver and
      preconditioning, as well as pharmacological strategies that simulated their
      benefits, such as anti-TNF and anti-MIP-2 therapies, could be new strategies
      aimed to reduce lung damage and inhibit the hepatic injury associated with
      hepatic ischemia-reperfusion.

PMID- 12057916
TI  - E- and N-cadherin distribution in developing and functional human teeth under
      normal and pathological conditions.
AB  - Cadherins are calcium-dependent cell adhesion molecules involved in the
      regulation of various biological processes such as cell recognition,
      intercellular communication, cell fate, cell polarity, boundary formation, and
      morphogenesis. Although previous studies have shown E-cadherin expression during
      rodent or human odontogenesis, there is no equivalent study available on N
      cadherin expression in dental tissues. Here we examined and compared the
      expression patterns of E- and N-cadherins in both embryonic and adult (healthy,
      injured, carious) human teeth. Both proteins were expressed in the developing
      teeth during the cap and bell stages. E-cadherin expression in dental epithelium
      followed an apical-coronal gradient that was opposite to that observed for N
      cadherin. E-cadherin was distributed in proliferating cells of the inner and
      outer enamel epithelia but not in differentiated cells such as ameloblasts,
      whereas N-cadherin expression was up-regulated in differentiated epithelial
      cells. By contrast to E-cadherin, N-cadherin was also expressed in mesenchymal
      cells that differentiate into odontoblasts and produce the hard tissue matrix of
      dentin. Although N-cadherin was not detected in permanent intact teeth, it was re
      expressed during dentin repair processes in odontoblasts surrounding carious or
      traumatic sites. Similarly, N-cadherin re-expression was seen in vitro, in
      cultured primary pulp cells that differentiate into odontoblast-like cells. Taken
      together these results suggest that E- and N-cadherins may play a role during
      human tooth development and, moreover, indicate that N-cadherin is important for
      odontoblast function in normal development and under pathological conditions.

PMID- 12057917
TI  - Integrin alpha 7 beta 1 in muscular dystrophy/myopathy of unknown etiology.
AB  - To investigate the role of integrin alpha 7 in muscle pathology, we used a
      "candidate gene" approach in a large cohort of muscular dystrophy/myopathy
      patients. Antibodies against the intracellular domain of the integrin alpha 7A
      and alpha 7B were used to stain muscle biopsies from 210 patients with muscular
      dystrophy/myopathy of unknown etiology. Levels of alpha 7A and alpha 7B integrin
      were found to be decreased in 35 of 210 patients (approximately 17%). In six of
      these patients no integrin alpha 7B was detected. Screening for alpha 7B mutation
      in 30 of 35 patients detected only one integrin alpha 7 missense mutation (the
      mutation on the second allele was not found) in a patient presenting with a
      congenital muscular dystrophy-like phenotype. No integrin alpha 7 gene mutations
      were identified in all of the other patients showing integrin alpha 7 deficiency.
      In the process of mutation analysis, we identified a novel integrin alpha 7
      isoform presenting 72-bp deletion. This isoform results from a partial deletion
      of exon 21 due to the use of a cryptic splice site generated by a G to A missense
      mutation at nucleotide position 2644 in integrin alpha 7 cDNA. This spliced
      isoform is present in about 12% of the chromosomes studied. We conclude that
      secondary integrin alpha 7 deficiency is rather common in muscular
      dystrophy/myopathy of unknown etiology, emphasizing the multiple mechanisms that
      may modulate integrin function and stability.

PMID- 12057918
TI  - Atherosclerotic lesions grow through recruitment and proliferation of circulating
      monocytes in a murine model.
AB  - Macrophage-derived foam cells in developing atherosclerotic lesions may
      potentially originate either from recruitment of circulating monocytes or from
      migration of resident tissue macrophages. In this study, we have determined the
      source of intimal macrophages in the apoE-knockout mouse flow
      cessation/hypercholesterolemia model of atherosclerosis using a bone marrow
      transplantation approach. We also examined the time course and spatial
      distribution of intercellular adhesion molecule-1 and vascular cell adhesion
      molecule-1 expression to assess whether endothelial adhesion molecules were
      involved in recruitment of either circulating monocytes or resident macrophages.
      We used allelic variants of the mouse common leukocyte antigen (CD45) to
      distinguish host-derived and donor-derived white blood cells (WBCs) both in blood
      and in macrophage-rich carotid lesions. We found that the distribution of CD45
      isoforms in lesions is similar to that of circulating WBCs, whereas the host-type
      CD45 isoform is more prevalent in resident adventitial macrophages. These data
      indicate that macrophage-derived foam cells in the lesion derive mainly from
      circulating precursors rather than from resident macrophages. The corresponding
      time course of intercellular adhesion molecule-1 and vascular cell adhesion
      molecule-1 expression suggests that recruitment of circulating WBCs by
      endothelial adhesion molecules is likely to be more important during lesion
      initiation than during the later phase of rapid lesion growth.

PMID- 12057919
TI  - Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with
      incomplete morphological evidence of papillary carcinoma: a search for the early
      precursors of papillary cancer.
AB  - Noninvasive thyroid nodules that exhibit borderline morphological signs of
      papillary cancer are difficult to diagnose and we do not know if they represent
      papillary carcinoma precursor lesions. Forty-six such nodules were analyzed for
      RET activation by immunohistochemistry and, in selected cases, by reverse
      transcriptase-polymerase chain reaction performed on RNA extracted after laser
      capture microdissection (LCM) of the tumor foci with and without papillary
      carcinoma features and positive RET immunoreactivity. RET immunoreactivity was
      identified, at least focally, in 30 of 46 (65.2%) of the nodules where it closely
      paralleled the morphological changes. Enough RNA was obtained after LCM in seven
      samples. RET/PTC1 or RET/PTC3 were detected in microscopic foci with papillary
      carcinoma features in most of the thyroid nodules (five of seven cases). No
      RET/PTC1 or RET/PTC3 rearrangements were detected in areas of the same tumors
      that lacked the cytological alterations. Analysis of clonality in the same
      nodules selected for LCM demonstrated that two were monoclonal and six were
      polyclonal. We conclude that RET activation closely parallels the morphological
      changes, that it is restricted to those areas of the tumor with the cytological
      alterations and that it is detectable in both mono- and polyclonal tumors.
      Although the finding of microscopic foci indicative of papillary carcinoma in a
      hyperplastic or adenomatous nodule does not justify the interpretation of the
      entire lesion as papillary carcinoma, it is possible that such foci may precede
      the development of invasive papillary cancer.

PMID- 12057920
TI  - Decrease and gain of gene expression are equally discriminatory markers for
      prostate carcinoma: a gene expression analysis on total and microdissected
      prostate tissue.
AB  - Information on over- and underexpressed genes in prostate cancer in comparison to
      adjacent normal tissue was sought by DNA microarray analysis. Approximately
      12,600 mRNA sequences were analyzed from a total of 26 tissue samples (17
      untreated prostate cancers, 9 normal adjacent to prostate cancer tissues)
      obtained by prostatectomy. Hierarchical clustering was performed. Expression
      levels of 63 genes were found significantly (at least 2.5-fold) increased,
      whereas expression of 153 genes was decreased (at least 2.5-fold) in prostate
      cancer versus adjacent normal tissue. In addition to previously described genes
      such as hepsin, overexpression of several genes was found that has not drawn
      attention before, such as the genes encoding the specific granule protein
      (SGP28), alpha-methyl-acyl-CoA racemase, low density lipoprotein (LDL)
      phospholipase A2, and the anti-apoptotic gene PYCR1. The radiosensitivity gene
      ATDC and the genes encoding the DNA-binding protein inhibitor ID1 and the
      phospholipase inhibitor uteroglobin were significantly down-regulated in the
      cancer samples. DNA microarray data for eight genes were confirmed quantitatively
      in five normal and five cancer tissues by real-time reverse transcriptase
      polymerase chain reaction with a high correlation between the two methods. Laser
      capture microdissection of epithelial and stromal compartments from cancer and
      histological normal specimens followed by an amplification protocol for low
      levels of RNA (<0.1 microg) allowed us to distinguish between gene expression
      profiles characteristic of epithelial cells and those typical of stroma. Most of
      the genes identified in the nonmicrodissected tumor material as up-regulated were
      indeed overexpressed in cancerous epithelium rather than in the stromal
      compartment. We conclude that development of prostate cancer is associated with
      down-regulation as well as up-regulation of genes that show complex differential
      regulation in epithelia and stroma. Some of the gene expression alterations
      identified in this study may prove useful in the development of novel diagnostic
      and therapeutic strategies.

PMID- 12057921
TI  - Gene expression in Wilms' tumor mimics the earliest committed stage in the
      metanephric mesenchymal-epithelial transition.
AB  - Wilms' tumor (WT) has been considered a prototype for arrested cellular
      differentiation in cancer, but previous studies have relied on selected markers.
      We have now performed an unbiased survey of gene expression in WTs using
      oligonucleotide microarrays. Statistical criteria identified 357 genes as
      differentially expressed between WTs and fetal kidneys. This set contained 124
      matches to genes on a microarray used by Stuart and colleagues (Stuart RO, Bush
      KT, Nigam SK: Changes in global gene expression patterns during development and
      maturation of the rat kidney. Proc Natl Acad Sci USA 2001, 98:5649-5654) to
      establish genes with stage-specific expression in the developing rat kidney.
      Mapping between the two data sets showed that WTs systematically overexpressed
      genes corresponding to the earliest stage of metanephric development, and
      underexpressed genes corresponding to later stages. Automated clustering
      identified a smaller group of 27 genes that were highly expressed in WTs compared
      to fetal kidney and heterologous tumor and normal tissues. This signature set was
      enriched in genes encoding transcription factors. Four of these, PAX2, EYA1,
      HBF2, and HOXA11, are essential for cell survival and proliferation in early
      metanephric development, whereas others, including SIX1, MOX1, and SALL2, are
      predicted to act at this stage. SIX1 and SALL2 proteins were expressed in the
      condensing mesenchyme in normal human fetal kidneys, but were absent (SIX1) or
      reduced (SALL2) in cells at other developmental stages. These data imply that the
      blastema in WTs has progressed to the committed stage in the mesenchymal
      epithelial transition, where it is partially arrested in differentiation. The WT
      signature set also contained the Wnt receptor FZD7, the tumor antigen PRAME, the
      imprinted gene NNAT and the metastasis-associated transcription factor E1AF.

PMID- 12057922
TI  - Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat
      hepatocytes and its role in regeneration and development of liver.
AB  - Previously pleiotrophin (PTN) was identified among proteins secreted by Swiss 3T3
      cells as a mitogen for cultured adult rat hepatocytes. The present study showed
      that the growth of rat hepatocytes was enhanced when cultured with rat hepatic
      stellate cells (HSCs). HSCs expressed PTN mRNA and secreted its protein in the co
      cultures. Recombinant PTN enhanced the growth of hepatocytes in culture,
      suggesting that HSCs stimulate the growth of hepatocytes through the action of
      PTN. To know the biological role of PTN in the growth of hepatocytes in vivo, we
      examined the expression of PTN in four regeneration models of adult liver and
      embryonic liver of rat. The expression of PTN mRNA in the liver was markedly up
      regulated by the treatment with D-galactosamine (GalN) or with
      acetylaminofluorene followed by partial hepatectomy. HSCs expressed PTN mRNA in
      response to GalN treatment and its protein was found on hepatocytes. The mRNA
      expression of N-syndecan, a PTN receptor, was up-regulated in GalN-treated
      hepatocytes. The mesenchymal cells in the septum transversum enclosing the
      embryonic liver, but not embryonic HSCs, expressed PTN mRNA. We suggest that PTN
      is secreted from activated adult HSCs and embryonic mesenchymal cells as a
      mitogen of parenchymal cells in adult and embryonic liver, respectively.

PMID- 12057923
TI  - Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle
      caveolae, and develop a severe cardiomyopathic phenotype.
AB  - The caveolin gene family consists of caveolins 1, 2, and 3. Caveolins 1 and 2 are
      co-expressed in many cell types, such as endothelial cells, fibroblasts, smooth
      muscle cells and adipocytes, where they form a heteroligomeric complex. In
      contrast, the expression of caveolin-3 is muscle-specific. Thus, the expression
      of caveolin-1 is required for caveolae formation in non-muscle cells, while the
      expression of caveolin-3 drives caveolae formation in striated muscle cell types
      (cardiac and skeletal). To create a truly caveolae-deficient mouse, we interbred
      Cav-1 null mice and Cav-3 null mice to generate Cav-1/Cav-3 double-knockout (Cav
      1/3 dKO) mice. Here, we report that Cav-1/3 dKO mice are viable and fertile,
      despite the fact that they lack morphologically identifiable caveolae in
      endothelia, adipocytes, smooth muscle cells, skeletal muscle fibers, and cardiac
      myocytes. We also show that these mice are deficient in all three caveolin gene
      products, as caveolin-2 is unstable in the absence of caveolin-1. Interestingly,
      Cav-1/3 dKO mice develop a severe cardiomyopathy. At 2 months of age, analysis of
      Cav-1/3 dKO hearts via gated magnetic resonance imaging reveals a dramatic
      increase in left ventricular wall thickness, as compared with Cav-1-KO, Cav-3 KO,
      and wild-type mice. Further functional analysis of Cav-1/3 dKO hearts via
      transthoracic echocardiography demonstrates hypertrophy and dilation of the left
      ventricle, with a significant decrease in fractional shortening. As predicted,
      Northern analysis of RNA derived from the left ventricle of Cav-1/3 dKO mice
      shows a dramatic up-regulation of the atrial natriuretic factor message, a well
      established biochemical marker of cardiac hypertrophy. Finally, histological
      analysis of Cav-1/3 dKO hearts reveals hypertrophy, disorganization, and
      degeneration of the cardiac myocytes, as well as chronic interstitial fibrosis
      and inflammation. Thus, dual ablation of both Cav-1 and Cav-3 genes in mice leads
      to a pleiotropic defect in caveolae formation and severe cardiomyopathy.

PMID- 12057924
TI  - Down-modulation of monocyte transendothelial migration and endothelial adhesion
      molecule expression by fibroblast growth factor: reversal by the anti-angiogenic
      agent SU6668.
AB  - Basic and acidic fibroblast growth factor (bFGF and aFGF, respectively) and
      vascular endothelial growth factor (VEGF) exert angiogenic actions and have a
      role in wound healing, inflammation, and tumor growth. Monocytes and endothelial
      cells are involved in these processes, but the effect of FGF and VEGF on monocyte
      endothelial cell interactions has not been defined. We observed that monocyte
      adhesion to resting or cytokine (tumor necrosis factor-alpha or interleukin-1
      alpha)-stimulated human umbilical vein endothelial cells (HUVECs) was markedly
      inhibited (40 to 65%) by culture (1 to 6 days) of HUVECs with aFGF or bFGF.
      Monocyte transendothelial migration induced by C5a and chemokines (MCP-1, SDF-1
      alpha, RANTES, MIP-1 alpha) was also suppressed (by 50 to 75%) on bFGF-stimulated
      HUVECs. VEGF did not have these effects at the concentrations used (10 to 20
      ng/ml), although like bFGF, it promoted HUVEC proliferation. Culture of HUVECs
      with bFGF and aFGF significantly down-regulated intercellular adhesion molecule
      1, vascular cell adhesion molecule-1, and E-selectin expression on resting or
      tumor necrosis factor-alpha-stimulated HUVECs, but had no influence on platelet
      endothelial cell adhesion molecule (PECAM)-1 and VE-cadherin expression. bFGF
      also inhibited MCP-1 production by HUVECs. The inhibitory effects of bFGF on
      monocyte transendothelial migration and adhesion molecule expression were
      reversed by SU6668, an anti-angiogenic agent and bFGF receptor tyrosine kinase
      inhibitor. Our results suggest that bFGF and aFGF may suppress endothelial
      dependent monocyte recruitment and thus have an anti-inflammatory action during
      angiogenesis in chronic inflammation but inhibit the immunoinflammatory tumor
      defense mechanism. However, SU6668 is an effective agent to prevent this down
      regulatory action of bFGF on monocyte-endothelial cell interactions.

PMID- 12057926
TI  - TRAP induces more intense tyrosine phosphorylation than thrombin with
      differential ultrastructural features.
AB  - We have analyzed modifications on platelet ultrastructural morphology,
      cytoskeletal assembly, and tyrosine phosphorylation developing in platelets
      activated by both thrombin and the thrombin receptor-activating peptide (TRAP).
      Washed platelets exposed to various concentrations of thrombin or TRAP, for
      different periods, were: fixed and examined by electron microscopy, or lysed and
      analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Under
      similar activating conditions, thrombin and TRAP induced different sequences of
      activation causing distinctive morphological and biochemical changes. Platelets
      exposed to thrombin showed centralized organelles encircled by constricted
      microtubule coils and granules secreting their contents through narrow channels
      of the open canalicular system. In contrast, activation by TRAP induced swelling
      of the open canalicular system with organelles remaining randomly dispersed and
      microtubules peripherally distributed. Compared to thrombin activation, TRAP
      induced higher rates of actin polymerization; increased association of actin
      binding protein, myosin, and alpha-actinin; and higher association of tyrosine
      phosphorylated proteins with the insoluble cytoskeletal fraction. Secretion of
      intragranule substances, measured as expression of P-selectin and lysosomal
      integral membrane protein at the surface level, were similar for both agonists at
      equivalent concentrations. Our biochemical observations indicate that TRAP causes
      more intense changes in signaling through tyrosine phosphorylation of proteins
      associated with the cytoskeletal fraction than thrombin. However, as derived from
      ultrastructural observations, TRAP seems to be less efficient in triggering
      cytoskeletal assembly and internal contraction in an organized manner in contrast
      with the natural protease.

PMID- 12057928
TI  - Life span extension by reduction in growth hormone-insulin-like growth factor-1
      axis in a transgenic rat model.
AB  - The longer life span in dwarf mice suggests that a reduction in the growth
      hormone (GH)-insulin-like growth factor (IGF)-1 axis retards aging and extends
      the life span in mammals. We tested this hypothesis in a transgenic strain of
      rats whose GH gene was suppressed by an anti-sense GH transgene. Male rats
      homozygous for the transgene (tg/tg) had a reduced number of pituitary GH cells,
      a lower plasma concentration of IGF-1, and a dwarf phenotype. Heterozygous rats
      (tg/-) had an intermediate phenotype in plasma IGF-1, food intake, and body
      weight between tg/tg and control (-/-) rats. The life span of tg/tg rats was 5 to
      10% shorter than -/- rats. In contrast, the life span of tg/- rats was 7 to 10%
      longer than -/- rats. Pathological analysis suggested that neoplasms caused
      earlier death in tg/tg rats; in contrast, tg/- rats had reduced nonneoplastic
      diseases and a prolonged life span. Immunological analysis revealed a smaller
      population and lower activity of splenic natural killer cells in tg/tg rats. The
      results of the present study support the hypothesis, but suggest that there is an
      optimal level of the GH-IGF-1 axis to maximize survival in mammals.

PMID- 12057927
TI  - Enterococcus faecalis induces inflammatory bowel disease in interleukin-10
      knockout mice.
AB  - Germ-free interleukin-10 knockout (IL-10 KO) mice developed inflammatory bowel
      disease (IBD) after they were colonized with a pure culture of Enterococcus
      faecalis. E. faecalis not only induced IBD (primarily in colon and rectum) but
      rectal dysplasia and adenocarcinoma was also found in the IL-10 KO mice.
      Conventional (complex-intestinal flora) IL-10 KO mice developed IBD within 10 to
      15 weeks of age and showed more pathology in the cecum (typhlitis) than we
      observed with E. faecalis-induced IBD in gnotobiotic IL-10 KO mice. Conversely,
      neither germ-free IL-10 mice nor IL-10 KO mice colonized as adults, with a pure
      culture of Candida albicans, Escherichia coli, Lactobacillus casei, L. reuteri,
      L. acidophilus, a Bifidobacterium sp., Lactococcus lactis, or a Bacillus sp.
      developed IBD during the 25- to 30-week study. E. faecalis is a common intestinal
      microbe of man and animals that can trigger IBD, dysplasia, and carcinoma in a
      genetically susceptible murine host.

PMID- 12057925
TI  - Synergistic up-regulation of vascular endothelial growth factor expression in
      murine macrophages by adenosine A(2A) receptor agonists and endotoxin.
AB  - Under normoxic conditions, macrophages from C57BL mice produce low levels of
      vascular endothelial growth factor (VEGF). Hypoxia stimulates VEGF expression by
      approximately 500%; interferon-gamma (IFN-gamma) with endotoxin
      [lipopolysaccharide (LPS)] also stimulates VEGF expression by approximately 50 to
      150% in an inducible nitric oxide synthase (iNOS)-dependent manner. Treatment of
      normoxic macrophages with 5'-N-ethyl-carboxamido-adenosine (NECA), a nonselective
      adenosine A(2) receptor agonist, or with 2-[p-(2-carboxyethyl)-phenylethyl amino]
      5'-N-ethyl-carboxamido-adenosine (CGS21680), a specific adenosine A(2A) receptor
      agonist, modestly increases VEGF expression, whereas 2-chloro-N(6)-cyclopentyl
      adenosine (CCPA), an adenosine A(1) agonist, does not. Treatment with LPS (0 to
      1000 ng/ml), or with IFN-gamma (0 to 300 U/ml), does not affect VEGF expression.
      In the presence of LPS (EC(50) < 10 ng/ml), but not of IFN-gamma, both NECA and
      CGS21680 synergistically up-regulate VEGF expression by as much as 10-fold. This
      VEGF is biologically active in vivo in the rat corneal bioassay of angiogenesis.
      Inhibitors of iNOS do not affect this synergistic induction of VEGF, and
      macrophages from iNOS-/- mice produce similar levels of VEGF as wild-type mice,
      indicating that NO does not play a role in this induction. Under hypoxic
      conditions, VEGF expression is slightly increased by adenosine receptor agonists
      but adenosine A(2) or A(1) receptor antagonists 3,7-dimethyl-1-propargyl xanthine
      (DMPX), ZM241385, and 8-cyclopentyl-1,3-dipropylxanthine (DCPCX) do not modulate
      VEGF expression. VEGF expression is also not reduced in hypoxic macrophages from
      A(3)-/- and A(2A)-/- mice. Thus, VEGF expression by hypoxic macrophages does not
      seem to depend on endogenously released or exogenous adenosine. VEGF expression
      is strongly up-regulated by LPS/NECA in macrophages from A(3)-/- but not A(2A)-/-
      mice, confirming the role of adenosine A(2A) receptors in this pathway. LPS with
      NECA strongly up-regulates VEGF expression by macrophages from C(3)H/HeN mice
      (with intact Tlr4 receptors), but not by macrophages from C(3)H/HeJ mice (with
      mutated, functionally inactive Tlr4 receptors), implicating signaling through the
      Tlr4 pathway in this synergistic up-regulation. Finally, Western blot analysis of
      adenosine A(2A) receptor expression indicated that the synergistic interaction of
      LPS with A(2A) receptor agonists does not involve up-regulation of A(2A)
      receptors by LPS. These results indicate that in murine macrophages there is a
      novel pathway regulating VEGF production, that involves the synergistic
      interaction of adenosine A(2A) receptor agonists through A(2A) receptors with LPS
      through the Tlr4 pathway, resulting in the strong up-regulation of VEGF
      expression by macrophages in a hypoxia- and NO-independent manner.

PMID- 12057929
TI  - Metallothionein-independent zinc protection from alcoholic liver injury.
AB  - Previous studies using metallothionein (MT)-overexpressing transgenic mice have
      demonstrated that MT protects the liver from oxidative injury induced by alcohol.
      The mechanism of action of MT is unknown. Because MT primarily binds to zinc
      under physiological conditions and releases zinc under oxidative stress and zinc
      is an antioxidant element, it is likely that zinc mediates the protective action
      of MT. The present study was undertaken to determine the distinct role of zinc in
      hepatic protection from alcoholic injury. MT I/II-knockout (MT-KO) mice along
      with their wild-type controls were treated with three gastric doses of ethanol at
      5 g/kg at 12-hour intervals. Zinc sulfate was injected intraperitoneally in a
      dosage of 5 mg/kg/day for 3 days before ethanol treatment. MT concentrations in
      MT-KO mice were very low and zinc concentrations in MT-KO mice were lower than in
      wild-type mice. Zinc treatment significantly elevated hepatic MT concentrations
      only in wild-type mice and increased zinc concentrations in both MT-KO and wild
      type mice. Ethanol treatment caused degenerative morphological changes and
      necrotic appearance in the livers of MT-KO mice. Microvesicular steatosis was the
      only ethanol-induced change in the liver of wild-type mice. Ethanol treatment
      decreased hepatic glutathione concentrations and increased hepatic lipid
      peroxidation, and the concentrations of lipid peroxide products in the wild-type
      mice were lower than in the MT-KO mice. All of these alcohol-induced toxic
      responses were significantly suppressed by zinc treatment in both MT-KO and wild
      type mouse livers. These results demonstrate that zinc, independent of MT, plays
      an important role in protection from alcoholic liver injury. However, MT is
      required to maintain high levels of zinc in the liver, suggesting that the
      protective action of MT in the liver is likely mediated by zinc.

PMID- 12057930
TI  - Lipoxins induce actin reorganization in monocytes and macrophages but not in
      neutrophils: differential involvement of rho GTPases.
AB  - Lipoxins (LXs) are endogenously produced eicosanoids that inhibit neutrophil
      trafficking and stimulate nonphlogistic phagocytosis of apoptotic neutrophils by
      monocyte-derived macrophages. In this study we assessed the effect of LXs on cell
      ultrastructure and actin reorganization in human leukocytes and investigated the
      signaling events that subserve LX bioactivity in this context. LXA(4) (10(-9)
      mol/L), the stable synthetic analogues 15-(R/S)-methyl-LXA(4) and 16-phenoxy
      LXA(4) (10(-11) mol/L), but not the LX precursor 15-(S)-HETE, induced marked
      changes in ultrastructure and rearrangement of actin in monocytes and
      macrophages. In contrast, LXA(4) did not modify actin distribution in neutrophils
      under basal conditions and after stimulation with leukotriene B(4). Blockade of
      Rho kinases by the inhibitor Y-27632 prevented LXA(4)-triggered actin
      reorganization in macrophages. To investigate the role of the specific small
      GTPases in LX-induced actin rearrangement we used THP-1 cells differentiated to a
      macrophage-like phenotype. THP-1 cells stimulated with LXs, but not with 15-(S)
      HETE, showed an increase in membrane-associated RhoA and Rac by immunoblotting.
      Additionally, a twofold increase in Rho activity was seen in response to LXA(4).
      LX-induced actin rearrangement and RhoA activation were inhibited by the cell
      permeable cAMP analogue 8-Br-cAMP, whereas Rp-cAMP, an inhibitor of protein
      kinase A, mimicked the effect of LXA(4). These data demonstrate that LXs
      stimulate RhoA- and Rac-dependent cytoskeleton reorganization, contributing to
      the potential role of LXs in the resolution of inflammation.

PMID- 12057931
TI  - Inflammatory cytokines, angiogenesis, and fibrosis in the rat peritoneum.
AB  - Peritonitis, a common complication of peritoneal dialysis, is followed by acute
      changes in the function of the peritoneum. The role of inflammatory cytokines in
      these processes is not clearly identified. We used adenoviral-mediated gene
      transfer to transiently overexpress interleukin (IL)-1 beta (AdIL-1 beta) or
      tumor necrosis factor (TNF)-alpha (AdTNF-alpha) in the rat peritoneum then used a
      modified equilibrium test to study the histological and functional changes.
      Overexpression of IL-1 beta or TNF-alpha led to an acute inflammatory response.
      Both inflammatory cytokines induced an early expression of the angiogenic
      cytokine, vascular endothelial growth factor, along with increased expression of
      the profibrotic cytokine, transforming growth factor-beta1, along with
      fibronectin expression and collagen deposition in peritoneal tissues. Both
      inflammatory cytokines induced angiogenesis, increased solute permeability, and
      ultrafiltration dysfunction at earlier time points. Changes in structure and
      function seen in AdTNF-alpha-treated animals returned to normal by 21 days after
      infection, whereas AdIL-1 beta-treated animals had persistently increased
      vasculature with submesothelial thickening and fibrosis. This was associated with
      up-regulation TIMP-1. TNF-alpha or IL-1 beta both induce acute changes in the
      peritoneum that mimic those seen in peritoneal dialysis patients who experience
      an episode of peritonitis. These functional changes were associated with early
      angiogenesis that resolved rapidly after exposure to TNF-alpha. IL-1 beta
      exposure, however, led to a different response with sustained vascularization and
      fibrosis. IL-1 beta inhibition may be a therapeutic goal in acute peritonitis to
      prevent peritoneal damage.

PMID- 12057932
TI  - A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast
      growth factor 19 in skeletal muscle of transgenic mice.
AB  - Most mouse models of hepatocellular carcinoma have expressed growth factors and
      oncogenes under the control of a liver-specific promoter. In contrast, we
      describe here the formation of liver tumors in transgenic mice overexpressing
      human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic
      mice had elevated hepatic alpha-fetoprotein mRNA as early as 2 months of age, and
      hepatocellular carcinomas were evident by 10 months of age. Increased
      proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'
      deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation
      and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small
      cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic
      foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive
      of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt
      pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear
      staining for beta-catenin. Sequencing of the tumor DNA encoding beta-catenin
      revealed point mutations that resulted in amino acid substitutions. These
      findings suggest a previously unknown role for FGF19 in hepatocellular
      carcinomas.

PMID- 12057933
TI  - Overexpression of Mcl-1 in anaplastic large cell lymphoma cell lines and tumors.

PMID- 12057934
TI  - Molecular characterization of the PceA reductive dehalogenase of
      desulfitobacterium sp. strain Y51.
AB  - The tetrachloroethene (PCE) reductive dehalogenase (encoded by the pceA gene and
      designated PceA dehalogenase) of Desulfitobacterium sp. strain Y51 was purified
      and characterized. The expression of the enzyme was highly induced in the
      presence of PCE and trichloroethene (TCE). The purified enzyme catalyzed the
      reductive dehalogenation of PCE via TCE to cis-1,2-dichloroethene at a specific
      activity of 113.6 nmol x min(-1) x mg of protein(-1). The apparent K(m) values
      for PCE and TCE were 105.7 and 535.3 microM, respectively. Chlorinated ethenes
      other than PCE and TCE were not dehalogenated. However, the enzyme exhibited
      dehalogenation activity for various chlorinated ethanes such as hexachloroethane,
      pentachloroethane, 1,1,1,2-tetrachloroethane, and 1,1,2,2-tetrachloroethane. The
      pceA gene of Desulfitobacterium sp. strain Y51 was identified in a 2.8-kb DNA
      fragment and used to express the protein in Escherichia coli for the preparation
      of antibodies. Immunoblot analyses located PceA in the periplasm of the cell.

PMID- 12057935
TI  - Competence without a competence pheromone in a natural isolate of Streptococcus
      infantis.
AB  - Many streptococcal species belonging to the mitis and anginosus phylogenetic
      groups are known to be naturally competent for genetic transformation. Induction
      of the competent state in these bacteria is regulated by a quorum-sensing
      mechanism consisting of a secreted peptide pheromone encoded by comC and a two
      component regulatory system encoded by comDE. Here we report that a natural
      isolate of a mitis group streptococcus (Atu-4) is competent for genetic
      transformation even though it has lost the gene encoding the competence
      pheromone. In contrast to other strains, induction of competence in Atu-4 is not
      regulated by cell density, since highly diluted cultures of this strain are still
      competent. Interestingly, competence in the Atu-4 strain is lost if the gene
      encoding the response regulator ComE is disrupted, demonstrating that this
      component of the quorum-sensing apparatus is still needed for competence
      development. These results indicate that mutations in ComD or ComE have resulted
      in a gain-of-function phenotype that allows competence without a competence
      pheromone. A highly similar strain lacking comC was isolated independently from
      another individual, suggesting that strains with this phenotype are able to
      survive in nature in competition with wild-type strains.

PMID- 12057936
TI  - Spa32 regulates a switch in substrate specificity of the type III secreton of
      Shigella flexneri from needle components to Ipa proteins.
AB  - Type III secretion systems (TTSS) are essential virulence determinants of many
      gram-negative bacteria and serve, upon physical contact with target cells, to
      translocate bacterial proteins directly across eukaryotic cell membranes. The
      Shigella TTSS is encoded by the mxi/spa loci located on its virulence plasmid. By
      electron microscopy secretons are visualized as tripartite with an external
      needle, a transmembrane domain, and a cytoplasmic bulb. In the present study, we
      generated a Shigella spa32 mutant and studied its phenotype. The spa32 gene shows
      low sequence homology to Salmonella TTSS1 invJ/spaN and to flagellar fliK. The
      spa32 mutant, like the wild-type strain, secreted the Ipas and IpgD, which are
      normally secreted via the TTSS, at low levels into the growth medium. However,
      unlike the wild-type strain, the spa32 mutant could neither be induced to secrete
      the Ipas and IpgD instantaneously upon addition of Congo red nor penetrate HeLa
      cells in vitro. Additionally, the Spa32 protein is secreted in large amounts by
      the TTSS during exponential growth but not upon Congo red induction.
      Interestingly, electron microscopy analysis of the spa32 mutant revealed that the
      needle of its secretons were up to 10 times longer than those of the wild type.
      In addition, in the absence of induction, the spa32 mutant secreted normal levels
      of MxiI but a large excess of MxiH. Taken together, our data indicate that the
      spa32 mutant presents a novel phenotype and that the primary defect of the mutant
      may be its inability to regulate or control secretion of MxiH.

PMID- 12057937
TI  - Natural transformation and DNA uptake signal sequences in Actinobacillus
      actinomycetemcomitans.
AB  - Actinobacillus actinomycetemcomitans is a member of the family Pasteurellaceae
      and a major causative agent of periodontitis. While several genera from this
      family are known to be competent for transformation, A. actinomycetemcomitans has
      yet to be fully characterized. Here we show that the competence of A.
      actinomycetemcomitans is remarkably similar to that of Haemophilus influenzae. In
      addition to having a similar frequency of transformation as H. influenzae, A.
      actinomycetemcomitans competence could also be induced at least 100-fold by
      cyclic AMP, suggesting that, as in H. influenzae, at least some competence genes
      are regulated by catabolite repression. Even more intriguing was the discovery of
      a putative A. actinomycetemcomitans DNA uptake signal sequence (USS) virtually
      identical to the USS of H. influenzae. Moreover, we provide evidence that this
      sequence functions in the same capacity as that from H. influenzae; the sequence
      appears to be required and sufficient for DNA uptake in a variety of assays.
      Finally, we have taken advantage of this system to develop a simple, highly
      efficient competence-based method for generating site-directed mutations in the
      wild-type fimbriated A. actinomycetemcomitans.

PMID- 12057938
TI  - pfs-dependent regulation of autoinducer 2 production in Salmonella enterica
      serovar Typhimurium.
AB  - Bacterial intercellular communication provides a mechanism for signal-dependent
      regulation of gene expression to promote coordinated population behavior.
      Salmonella enterica serovar Typhimurium produces a non-homoserine lactone
      autoinducer in exponential phase as detected by a Vibrio harveyi reporter assay
      for autoinducer 2 (AI-2) (M. G. Surette and B. L. Bassler, Proc. Natl. Acad. Sci.
      USA 95:7046-7050, 1998). The luxS gene product mediates the production of AI-2
      (M. G. Surette, M. B. Miller, and B. L. Bassler, Proc. Natl. Acad. Sci. USA
      96:1639-1644, 1999). Environmental cues such as rapid growth, the presence of
      preferred carbon sources, low pH, and/or high osmolarity were found to influence
      the production of AI-2 (M. G. Surette and B. L. Bassler, Mol. Microbiol. 31:585
      595, 1999). In addition to LuxS, the pfs gene product (Pfs) is required for AI-2
      production, as well as S-adenosylhomocysteine (SAH) (S. Schauder, K. Shokat, M.
      G. Surette, and B. L. Bassler, Mol. Microbiol. 41:463-476, 2001). In bacterial
      cells, Pfs exhibits both 5'-methylthioadenosine (MTA) and SAH nucleosidase
      functions. Pfs is involved in methionine metabolism, regulating intracellular MTA
      and SAH levels (elevated levels of MTA and SAH are potent inhibitors of polyamine
      synthetases and S-adenosylmethionine dependent methyltransferase reactions,
      respectively). To further investigate regulation of AI-2 production in
      Salmonella, we constructed pfs and luxS promoter fusions to a luxCDABE reporter
      in a low-copy-number vector, allowing an examination of transcription of the
      genes in the pathway for signal synthesis. Here we report that luxS expression is
      constitutive but that the transcription of pfs is tightly correlated to AI-2
      production in Salmonella serovar Typhimurium 14028. Neither luxS nor pfs
      expression appears to be regulated by AI-2. These results suggest that AI-2
      production is regulated at the level of LuxS substrate availability and not at
      the level of luxS expression. Our results indicate that AI-2-dependent signaling
      is a reflection of metabolic state of the cell and not cell density.

PMID- 12057939
TI  - The type IV pilus assembly complex: biogenic interactions among the bundle
      forming pilus proteins of enteropathogenic Escherichia coli.
AB  - Production of type IV bundle-forming pili (BFP) by enteropathogenic Escherichia
      coli (EPEC) requires the protein products of 12 genes of the 14-gene bfp operon.
      Antisera against each of these proteins were used to demonstrate that in-frame
      deletion of individual genes within the operon reduces the abundance of other bfp
      operon-encoded proteins. This result was demonstrated not to be due to downstream
      polar effects of the mutations but rather was taken as evidence for protein
      protein interactions and their role in the stabilization of the BFP assembly
      complex. These data, combined with the results of cell compartment localization
      studies, suggest that pilus formation requires the presence of a topographically
      discrete assembly complex that is composed of BFP proteins in stoichiometric
      amounts. The assembly complex appears to consist of an inner membrane component
      containing three processed, pilin-like proteins, BfpI, -J, and -K, that localize
      with BfpE, -L, and -A (the major pilin subunit); an outer membrane, secretin-like
      component, BfpB and -G; and a periplasmic component composed of BfpU. Of these,
      only BfpL consistently localizes with both the inner and outer membranes and
      thus, together with BfpU, may articulate between the Bfp proteins in the inner
      membrane and outer membrane compartments.

PMID- 12057940
TI  - Identification of two quorum-sensing systems in Sinorhizobium meliloti.
AB  - Sinorhizobium meliloti is a free-living soil bacterium which is capable of
      establishing a symbiotic relationship with the alfalfa plant (Medicago sativa).
      This symbiosis involves a network of bacterium-host signaling, as well as the
      potential for bacterium-bacterium communication, such as quorum sensing. In this
      study, we characterized the production of N-acyl homoserine lactones (AHLs) by
      two commonly used S. meliloti strains, AK631 and Rm1021. We found that AK631
      produces at least nine different AHLs, while Rm1021 produces only a subset of
      these molecules. To address the difference in AHL patterns between the strains,
      we developed a novel screening method to identify the genes affecting AHL
      synthesis. With this screening method, chromosomal groEL (groELc) was shown to be
      required for synthesis of the AHLs that are unique to AK631 but not for synthesis
      of the AHLs that are made by both AK631 and Rm1021. We then used the screening
      procedure to identify a mutation in a gene homologous to traM of Agrobacterium
      tumefaciens, which was able to suppress the phenotype of the groELc mutation. A
      traR homolog was identified immediately upstream of traM, and we propose that its
      gene product requires a functional groELc for activity and is also responsible
      for inducing the synthesis of the AHLs that are unique to AK631. We show that the
      traR/traM locus is part of a quorum-sensing system unique to AK631 and propose
      that this locus is involved in regulating conjugal plasmid transfer. We also
      present evidence for the existence of a second quorum-sensing system, sinR/sinI,
      which is present in both AK631 and Rm1021.

PMID- 12057941
TI  - Chloromethane-induced genes define a third C1 utilization pathway in
      Methylobacterium chloromethanicum CM4.
AB  - Methylobacterium chloromethanicum CM4 is an aerobic alpha-proteobacterium capable
      of growth with chloromethane as the sole carbon and energy source. Two proteins,
      CmuA and CmuB, were previously purified and shown to catalyze the dehalogenation
      of chloromethane and the vitamin B12-mediated transfer of the methyl group of
      chloromethane to tetrahydrofolate. Three genes located near cmuA and cmuB,
      designated metF, folD and purU and encoding homologs of methylene
      tetrahydrofolate (methylene-H4folate) reductase, methylene-H4folate dehydrogenase
      methenyl-H4folate cyclohydrolase and formyl-H4folate hydrolase, respectively,
      suggested the existence of a chloromethane-specific oxidation pathway from methyl
      tetrahydrofolate to formate in strain CM4. Hybridization and PCR analysis
      indicated that these genes were absent in Methylobacterium extorquens AM1, which
      is unable to grow with chloromethane. Studies with transcriptional xylE fusions
      demonstrated the chloromethane-dependent expression of these genes.
      Transcriptional start sites were mapped by primer extension and allowed to define
      three transcriptional units, each likely comprising several genes, that were
      specifically expressed during growth of strain CM4 with chloromethane. The DNA
      sequences of the deduced promoters display a high degree of sequence conservation
      but differ from the Methylobacterium promoters described thus far. As shown
      previously for purU, inactivation of the metF gene resulted in a CM4 mutant
      unable to grow with chloromethane. Methylene-H4folate reductase activity was
      detected in a cell extract of strain CM4 only in the presence of chloromethane
      but not in the metF mutant. Taken together, these data provide evidence that M.
      chloromethanicum CM4 requires a specific set of tetrahydrofolate-dependent
      enzymes for growth with chloromethane.

PMID- 12057942
TI  - Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and
      proteome analysis of cellular and extracellular proteins.
AB  - The events involved in the establishment of a latent infection with Mycobacterium
      tuberculosis are not fully understood, but hypoxic conditions are generally
      believed to be the environment encountered by the pathogen in the central part of
      the granuloma. The present study was undertaken to provide insight into M.
      tuberculosis protein expression in in vitro latency models where oxygen is
      depleted. The response of M. tuberculosis to low-oxygen conditions was
      investigated in both cellular and extracellular proteins by metabolic labeling,
      two-dimensional electrophoresis, and protein signature peptide analysis by liquid
      chromatography-mass spectrometry. By peptide mass fingerprinting and
      immunodetection, five proteins more abundant under low-oxygen conditions were
      identified from several lysates of M. tuberculosis: Rv0569, Rv2031c (HspX),
      Rv2623, Rv2626c, and Rv3841 (BfrB). In M. tuberculosis culture filtrates, two
      additional proteins, Rv0363c (Fba) and Rv2780 (Ald), were found in increased
      amounts under oxygen limitation. These results extend our understanding of the
      hypoxic response in M. tuberculosis and potentially provide important insights
      into the physiology of the latent bacilli.

PMID- 12057943
TI  - Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation
      pathway in Ralstonia eutropha JMP134.
AB  - Ralstonia eutropha JMP134 can grow on several chlorinated aromatic pollutants,
      including 2,4-dichlorophenoxyacetate and 2,4,6-trichlorophenol (2,4,6-TCP).
      Although a 2,4,6-TCP degradation pathway in JMP134 has been proposed, the enzymes
      and genes responsible for 2,4,6-TCP degradation have not been characterized. In
      this study, we found that 2,4,6-TCP degradation by JMP134 was inducible by 2,4,6
      TCP and subject to catabolic repression by glutamate. We detected 2,4,6-TCP
      degrading activities in JMP134 cell extracts. Our partial purification and
      initial characterization of the enzyme indicated that a reduced flavin adenine
      dinucleotide (FADH2)-utilizing monooxygenase converted 2,4,6-TCP to 6
      chlorohydroxyquinol (6-CHQ). The finding directed us to PCR amplify a 3.2-kb
      fragment containing a gene cluster (tcpABC) from JMP134 by using primers designed
      from conserved regions of FADH2-utilizing monooxygenases and hydroxyquinol 1,2
      dioxygenases. Sequence analysis indicated that tcpA, tcpB, and tcpC encoded an
      FADH2-utilizing monooxygenase, a probable flavin reductase, and a 6-CHQ 1,2
      dioxygenase, respectively. The three genes were individually inactivated in
      JMP134. The tcpA mutant failed to degrade 2,4,6-TCP, while both tcpB and tcpC
      mutants degraded 2,4,6-TCP to an oxidized product of 6-CHQ. Insertional
      inactivation of tcpB may have led to a polar effect on downstream tcpC, and this
      probably resulted in the accumulation of the oxidized form of 6-CHQ. For further
      characterization, TcpA was produced, purified, and shown to transform 2,4,6-TCP
      to 6-CHQ when FADH2 was supplied by an Escherichia coli flavin reductase. TcpC
      produced in E. coli oxidized 6-CHQ to 2-chloromaleylacetate. Thus, our data
      suggest that JMP134 transforms 2,4,6-TCP to 2-chloromaleylacetate by TcpA and
      TcpC. Sequence analysis suggests that tcpB may function as an FAD reductase, but
      experimental data did not support this hypothesis. The function of TcpB remains
      unknown.

PMID- 12057944
TI  - Nitric oxide-induced homologous recombination in Escherichia coli is promoted by
      DNA glycosylases.
AB  - Nitric oxide (NO*) is involved in neurotransmission, inflammation, and many other
      biological processes. Exposure of cells to NO* leads to DNA damage, including
      formation of deaminated and oxidized bases. Apurinic/apyrimidinic (AP)
      endonuclease-deficient cells are sensitive to NO* toxicity, which indicates that
      base excision repair (BER) intermediates are being generated. Here, we show that
      AP endonuclease-deficient cells can be protected from NO* toxicity by
      inactivation of the uracil (Ung) or formamidopyrimidine (Fpg) DNA glycosylases
      but not by inactivation of a 3-methyladenine (AlkA) DNA glycosylase. These
      results suggest that Ung and Fpg remove nontoxic NO*-induced base damage to
      create BER intermediates that are toxic if they are not processed by AP
      endonucleases. Our next goal was to learn how Ung and Fpg affect susceptibility
      to homologous recombination. The RecBCD complex is critical for repair of double
      strand breaks via homologous recombination. When both Ung and Fpg were
      inactivated in recBCD cells, survival was significantly enhanced. We infer that
      both Ung and Fpg create substrates for recombinational repair, which is
      consistent with the observation that disrupting ung and fpg suppressed NO*
      induced recombination. Taken together, a picture emerges in which the action of
      DNA glycosylases on NO*-induced base damage results in the accumulation of BER
      intermediates, which in turn can induce homologous recombination. These studies
      shed light on the underlying mechanism of NO*-induced homologous recombination.

PMID- 12057946
TI  - Involvement of the PrrB/PrrA two-component system in nitrite respiration in
      Rhodobacter sphaeroides 2.4.3: evidence for transcriptional regulation.
AB  - Rhodobacter sphaeroides strain 2.4.3 is capable of diverse metabolic lifestyles,
      including denitrification. The regulation of many Rhodobacter genes involved in
      redox processes is controlled, in part, by the PrrBA two-component sensor
      regulator system, where PrrB serves as the sensor kinase and PrrA is the response
      regulator. Four strains of 2.4.3 carrying mutations within the prrB gene were
      isolated in a screen for mutants unable to grow anaerobically on medium
      containing nitrite. Studies revealed that the expression of nirK, the structural
      gene encoding nitrite reductase, in these strains was significantly decreased
      compared to its expression in 2.4.3. Disruption of prrA also eliminated the
      ability to grow both photosynthetically and anaerobically in the dark on nitrite
      amended medium. Complementation with prrA restored the wild-type phenotype. The
      PrrA strain exhibited a severe decrease in both nitrite reductase activity and
      expression of a nirK-lacZ fusion. Nitrite reductase activity in the PrrA strain
      could be restored to wild-type levels by using nirK expressed from a heterologous
      promoter, suggesting that the loss of nitrite reductase activity in the PrrA and
      PrrB mutants was not due to problems with enzyme assembly or the supply of
      reductant. Inactivation of prrA had no effect on the expression of the gene
      encoding NnrR, a transcriptional activator required for the expression of nirK.
      Inactivation of ccoN, part of the cbb(3)-type cytochrome oxidase shown to
      regulate the kinase activity of PrrB, also caused a significant decrease in both
      nirK expression and Nir activity. This was unexpected, since PrrA-P accumulates
      in the ccoN strain. Together, these results demonstrate that PrrBA plays an
      essential role in the regulation of nirK.

PMID- 12057945
TI  - Global transcriptional analysis of clpP mutations of type 2 Streptococcus
      pneumoniae and their effects on physiology and virulence.
AB  - Streptococcus pneumoniae is an important human pathogen that contains single
      copies of genes encoding the ClpP and FtsH ATP-dependent proteases but lacks the
      Lon and HslV proteases. We constructed and characterized the phenotypes of clpP,
      clpC, and clpX deletion replacement mutants, which lack the ClpP protease subunit
      or the putative ClpC or ClpX ATPase specificity factor. A DeltaclpP mutant, but
      not a DeltaclpC or DeltaclpX mutant, of the virulent D39 type 2 strain of S.
      pneumoniae grew poorly at 30 degrees C and failed to grow at 40 degrees C.
      Despite this temperature sensitivity, transcription of the heat shock regulon
      determined by microarray analysis was induced in a DeltaclpP mutant, which was
      also more sensitive to oxidative stress by H2O2 and to puromycin than its clpP+
      parent strain. A DeltaclpP mutant, but not a DeltaclpC mutant, was strongly
      attenuated for virulence in the murine lung and sepsis infection models. All of
      these phenotypes were complemented in a DeltaclpP/clpP+ merodiploid strain.
      Consistent with these complementation patterns, clpP was found to be in a
      monocistronic operon, whose transcription was induced about fivefold by heat
      shock in S. pneumoniae as determined by Northern and real-time reverse
      transcription-PCR analyses. Besides clpP, transcription of clpC, clpE, and clpL,
      but not clpX or ftsH, was induced by heat shock or entry into late exponential
      growth phase. Microarray analysis of DeltaclpP mutants showed a limited change in
      transcription pattern (approximately 80 genes) consistent with these phenotypes,
      including repression of genes involved in oxidative stress, metal ion transport,
      and virulence. In addition, transcription of the early and late competence
      regulon was induced in the DeltaclpP mutant, and competence gene expression and
      DNA uptake seemed to be constitutively induced throughout growth. Together, these
      results indicate that ClpP-mediated proteolysis plays a complex and central role
      in numerous pneumococcal stress responses, development of competence, and
      virulence.

PMID- 12057947
TI  - Roles for sigma factors in global circadian regulation of the cyanobacterial
      genome.
AB  - The circadian clock of the unicellular cyanobacterium Synechococcus elongatus PCC
      7942 imposes a global rhythm of transcription on promoters throughout the genome.
      Inactivation of any of the four known group 2 sigma factor genes (rpoD2, rpoD3,
      rpoD4, and sigC), singly or pairwise, altered circadian expression from the psbAI
      promoter, changing amplitude, phase angle, waveform, or period. However, only the
      rpoD2 mutation and the rpoD3 rpoD4 and rpoD2 rpoD3 double mutations affected
      expression from the kaiB promoter. A striking differential effect was a 2-h
      lengthening of the circadian period of expression from the promoter of psbAI, but
      not of those of kaiB or purF, when sigC was inactivated. The data show that
      separate timing circuits with different periods can coexist in a cell.
      Overexpression of rpoD2, rpoD3, rpoD4, or sigC also changed the period or
      abolished the rhythmicity of PpsbAI expression, consistent with a model in which
      sigma factors work as a consortium to convey circadian information to downstream
      genes.

PMID- 12057948
TI  - Genetic locus encoding functions involved in biosynthesis and outer membrane
      localization of xanthomonadin in Xanthomonas oryzae pv. oryzae.
AB  - Xanthomonadins are membrane-bound, brominated, aryl-polyene pigments specific to
      the genus Xanthomonas. We have characterized a genetic locus (pig) from
      Xanthomonas oryzae pv. oryzae which contains four open reading frames (ORFs) that
      are essential for xanthomonadin production. Three of these ORFs are homologous to
      acyl carrier proteins, dehydratases, and acyl transferases, suggesting a type II
      polyketide synthase pathway for xanthomonadin biosynthesis. The fourth ORF has no
      homologue in the database. For the first time, we report that a putative
      cytoplasmic membrane protein encoded in the pig locus is required for outer
      membrane localization of xanthomonadin in X. oryzae pv. oryzae. We also report
      the identification of a novel 145-bp palindromic Xanthomonas repetitive
      intergenic consensus element that is present in two places in the pig locus. We
      estimate that more than 100 copies of this element might be present in the genome
      of X. oryzae pv. oryzae and other xanthomonads.

PMID- 12057949
TI  - Differential regulation of multiple proteins of Escherichia coli and Salmonella
      enterica serovar Typhimurium by the transcriptional regulator SlyA.
AB  - SlyA is a transcriptional regulator of Escherichia coli, Salmonella enterica, and
      other bacteria belonging to the ENTEROBACTERIACEAE: The SlyA protein has been
      shown to be involved in the virulence of S. enterica serovar Typhimurium, but its
      role in E. coli is unclear. In this study, we employed the proteome technology to
      analyze the SlyA regulons of enteroinvasive E. coli (EIEC) and Salmonella serovar
      Typhimurium. In both cases, comparative analysis of the two-dimensional protein
      maps of a wild-type strain, a SlyA-overproducing derivative, and a corresponding
      slyA mutant revealed numerous proteins whose expression appeared to be either
      positively or negatively controlled by SlyA. Twenty of the putative SlyA-induced
      proteins and 13 of the putative SlyA-repressed proteins of the tested EIEC strain
      were identified by mass spectrometry. The former proteins included several
      molecular chaperones (GroEL, GroES, DnaK, GrpE, and CbpA), proteins involved in
      acid resistance (HdeA, HdeB, and GadA), the "starvation lipoprotein" (Slp),
      cytolysin ClyA (HlyE or SheA), and several enzymes involved in metabolic
      pathways, whereas most of the latter proteins proved to be biosynthetic enzymes.
      Consistently, the resistance of the EIEC slyA mutant to heat and acid stress was
      impaired compared to that of the wild-type strain. Furthermore, the implication
      of SlyA in the regulation of several of the identified E. coli proteins was
      confirmed at the level of transcription with lacZ fusions. Twenty-three of the
      Salmonella serovar Typhimurium proteins found to be affected by SlyA were also
      identified by mass spectrometry. With the exception of GroEL these differed from
      those identified in the EIEC strain and included proteins involved in various
      processes. The data suggest that gene regulation by SlyA might be crucial for
      intracellular survival and/or replication of both EIEC and Salmonella serovar
      Typhimurium in phagocytic host cells.

PMID- 12057950
TI  - The Rhizobium etli cyaC product: characterization of a novel adenylate cyclase
      class.
AB  - Adenylate cyclases (ACs) catalyze the formation of 3',5'-cyclic AMP (cAMP) from
      ATP. A novel AC-encoding gene, cyaC, was isolated from Rhizobium etli by
      phenotypic complementation of an Escherichia coli cya mutant. The functionality
      of the cyaC gene was corroborated by its ability to restore cAMP accumulation in
      an E. coli cya mutant. Further, overexpression of a malE::cyaC fusion protein
      allowed the detection of significant AC activity levels in cell extracts of an E.
      coli cya mutant. CyaC is unrelated to any known AC or to any other protein
      exhibiting a currently known function. Thus, CyaC represents the first member of
      a novel class of ACs (class VI). Hypothetical genes of unknown function similar
      to cyaC have been identified in the genomes of the related bacterial species
      Mesorhizobium loti, Sinorhizobium meliloti, and Agrobacterium tumefaciens. The
      cyaC gene is cotranscribed with a gene similar to ohr of Xanthomonas campestris
      and is expressed only in the presence of organic hydroperoxides. The
      physiological performance of an R. etli cyaC mutant was indistinguishable from
      that of the wild-type parent strain both under free-living conditions and during
      symbiosis.

PMID- 12057951
TI  - Substrate specificity of nickel/cobalt permeases: insights from mutants altered
      in transmembrane domains I and II.
AB  - HoxN, a high-affinity, nickel-specific permease of Ralstonia eutropha H16, and
      NhlF, a nickel/cobalt permease of Rhodococcus rhodochrous J1, are structurally
      related members of the nickel/cobalt transporter (NiCoT) family. These
      transporters have an eight-helix structure and are characterized by highly
      conserved segments with polar or charged amino acid residues in transmembrane
      domains (TMDs) II, III, V, and VI. Two histidine residues in a Ni2+ binding
      motif, the signature sequence of NiCoTs, in TMD II of HoxN have been shown to be
      crucial for activity. Replacement of the corresponding His residues in NhlF
      affected both Co2+ and Ni2+ uptake, demonstrating that NhlF employs a HoxN-like
      mechanism for transport of the two cations. Multiple alignments of bacterial
      NiCoT sequences identified a striking correlation between a hydrophobic residue
      (Val or Phe) in TMD II and a position in the center of TMD I occupied by either
      an Asn (as in HoxN) or a His (as in NhlF). Introducing an isoleucine residue at
      the latter position strongly reduced HoxN activity and abolished NhlF activity,
      suggesting that a Lewis base N-donor moiety is important. The Asn-to-His exchange
      had no effect on HoxN, whereas the converse replacement reduced NhlF-mediated
      Ni2+ uptake significantly. Replacement of the entire TMD I of HoxN by the
      respective NhlF segment resulted in a chimera that transported Ni2+ and Co2+ with
      low capacity. The Val-to-Phe exchange in TMD II of HoxN led to a considerable
      rise in Ni2+ uptake capacity and conferred to the variant the ability to
      transport Co2+. NhlF activity dropped in response to the converse mutation. Our
      data predict that TMDs I and II in NiCoTs spatially interact to form a critical
      part of the selectivity filter. As seen for the V64F variant of HoxN,
      modification of this site can increase the velocity of transport and
      concomitantly reduce the specificity.

PMID- 12057952
TI  - An adenylyl cyclase, CyaA, of Myxococcus xanthus functions in signal transduction
      during osmotic stress.
AB  - An adenylyl cyclase gene (cyaA) present upstream of an osmosensor protein gene
      (mokA) was isolated from Myxococcus xanthus. cyaA encoded a polypeptide of 843
      amino acids with a predicted molecular mass of 91,187 Da. The predicted cyaA gene
      product had structural similarity to the receptor-type adenylyl cyclases that are
      composed of an amino-terminal sensor domain and a carboxy-terminal catalytic
      domain of adenylyl cyclase. In reverse transcriptase PCR experiments, the
      transcript of the cyaA gene was detected mainly during development and spore
      germination. A cyaA mutant, generated by gene disruption, showed normal growth,
      development, and germination. However, a cyaA mutant placed under conditions of
      ionic (NaCl) or nonionic (sucrose) osmostress exhibited a marked reduction in
      spore formation and spore germination. When wild-type and cyaA mutant cells at
      developmental stages were stimulated with 0.2 M NaCl or sucrose, the mutant cells
      increased cyclic AMP accumulation at levels similar to those of the wild-type
      cells. In contrast, the mutant cells during spore germination had mainly lost the
      ability to respond to high-ionic osmolarity. In vegetative cells, the cyaA mutant
      responded normally to osmotic stress. These results suggested that M. xanthus
      CyaA functions mainly as an ionic osmosensor during spore germination and that
      CyaA is also required for osmotic tolerance in fruiting formation and
      sporulation.

PMID- 12057953
TI  - Northern, morphological, and fermentation analysis of spo0A inactivation and
      overexpression in Clostridium acetobutylicum ATCC 824.
AB  - The Clostridium acetobutylicum ATCC 824 spo0A gene was cloned, and two
      recombinant strains were generated, an spo0A inactivation strain (SKO1) and an
      spo0A overexpression strain [824(pMPSOA)]. SKO1 was developed by targeted gene
      inactivation with a replicative plasmid capable of double-crossover chromosomal
      integration--a technique never used before with solventogenic clostridia. SKO1
      was severely deficient in solvent formation: it produced only 2 mM acetone and 13
      mM butanol, compared to the 92 mM acetone and 172 mM butanol produced by the
      parental strain. After 72 h of growth on solid media, SKO1 formed long filaments
      of rod-shaped cells that failed to septate. SKO1 cells never achieved the swollen
      clostridial form typical of the parental strain and did not form endospores. No
      spo0A transcripts were detected in SKO1, while transcription of two solvent
      formation operons (aad-ctfA-ctfB and adc; both containing 0A boxes in their
      promoter regions) was limited. Strain 824(pMSPOA) produced higher butanol
      concentrations than the control strain [824(pIMP1)] and dramatically elevated
      spo0A transcript levels and displayed a bimodal pattern of spo0A transcription
      similar to that of B. subtilis. Microscopic studies indicated that sporulation
      was both enhanced and accelerated due to spo0A overexpression compared to that of
      both the 824(pIMP1) and parental strains. Consistent with that, expression of the
      key solvent formation genes (aad-ctfA-ctfB and adc) and three sporulation
      specific genes (spoIIGA, sigE, and sigG) was observed earlier in strain
      824(pMSPOA) than in the plasmid control. These data support the hypothesis that
      Spo0A is a transcriptional regulator that positively controls sporulation and
      solvent production. Its effect on solvent formation is a balancing act in
      regulating sporulation versus solvent gene expression: its overexpression
      apparently tips the balance in favor of accelerated and enhanced sporulation at
      the expense of overall solvent production.

PMID- 12057954
TI  - Quorum sensing is not required for twitching motility in Pseudomonas aeruginosa.
AB  - It has been reported that mutations in the quorum-sensing genes lasI and rhlI in
      Pseudomonas aeruginosa result in, among many other things, loss of twitching
      motility (A. Glessner, R. S. Smith, B. H. Iglewski, and J. B. Robinson, J.
      Bacteriol. 181:1623-1629, 1999). We constructed knockouts of lasI and rhlI and
      the corresponding regulatory genes lasR and rhlR and found no effect on twitching
      motility. However, twitching-defective variants accumulated during culturing of
      lasI and rhlI mutants. Further analysis showed that the stable twitching
      defective variants of lasI and rhlI mutants had arisen as a consequence of
      secondary mutations in vfr and algR, respectively, both of which encode key
      regulators affecting a variety of phenotypes, including twitching motility. In
      addition, when grown in shaking broth culture, lasI and rhlI mutants, but not the
      wild-type parent, also accumulated unstable variants that lacked both twitching
      motility and swimming motility and appeared to be identical in phenotype to the
      S1 and S2 variants that were recently reported to occur at high frequencies in P.
      aeruginosa strains grown as a biofilm or in static broth culture (E. Deziel, Y.
      Comeau, and R. Villemur, J. Bacteriol. 183:1195-1204, 2001). These results
      indicate that mutations in one regulatory system may create distortions that
      select during subsequent culturing for compensatory mutations in other regulatory
      genes within the cellular network. This problem may have compromised some past
      studies of regulatory hierarchies controlled by quorum sensing and of bacterial
      regulatory systems in general.

PMID- 12057955
TI  - Differential regulation of twitching motility and elastase production by Vfr in
      Pseudomonas aeruginosa.
AB  - Vfr, a homolog of Escherichia coli cyclic AMP (cAMP) receptor protein, has been
      shown to regulate quorum sensing, exotoxin A production, and regA transcription
      in Pseudomonas aeruginosa. We identified a twitching motility-defective mutant
      that carries a transposon insertion in vfr and confirmed that vfr is required for
      twitching motility by construction of an independent allelic deletion-replacement
      mutant of vfr that exhibited the same phenotype, as well as by the restoration of
      normal twitching motility by complementation of these mutants with wild-type vfr.
      Vfr-null mutants exhibited severely reduced twitching motility with barely
      detectable levels of type IV pili, as well as loss of elastase production and
      altered pyocyanin production. We also identified reduced-twitching variants of
      quorum-sensing mutants (PAK lasI::Tc) with a spontaneous deletion in vfr (S. A.
      Beatson, C. B. Whitchurch, A. B. T. Semmler, and J. S. Mattick, J. Bacteriol.,
      184:3598-3604, 2002), the net result of which was the loss of five residues
      (EQERS) from the putative cAMP-binding pocket of Vfr. This allele (VfrDeltaEQERS)
      was capable of restoring elastase and pyocyanin production to wild-type levels in
      vfr-null mutants but not their defects in twitching motility. Furthermore,
      structural analysis of Vfr and VfrDeltaEQERS in relation to E. coli CRP suggests
      that Vfr is capable of binding both cAMP and cyclic GMP whereas VfrDeltaEQERS is
      only capable of responding to cAMP. We suggest that Vfr controls twitching
      motility and quorum sensing via independent pathways in response to these
      different signals, bound by the same cyclic nucleotide monophosphate-binding
      pocket.

PMID- 12057957
TI  - Type 1 capsule genes of Staphylococcus aureus are carried in a staphylococcal
      cassette chromosome genetic element.
AB  - The cap1 genes are required for the synthesis of type 1 capsular polysaccharide
      (CP1) in Staphylococcus aureus. We previously showed that the cap1 locus was
      associated with a discrete genetic element in S. aureus M. In this report, we
      defined the boundaries of the cap1 element by comparing its restriction pattern
      to that of a corresponding region from the CP1-negative strain Becker. The
      element was located in the SmaI-G chromosomal fragment of the standard mapping
      strain NCTC8325. The sequences of the entire cap1 element and the flanking
      regions were determined. We found that there were two additional cap1 genes not
      previously identified. The cap1 operon was located in a staphylococcal cassette
      chromosome (SCC) element similar to the resistance island SCCmec recently
      described for methicillin resistance in S. aureus. Notably, the SCCcap1 element
      was located at the same insertion site as all the SCCmec elements in the
      staphylococcal chromosome. The excision of SCCcap1 could be demonstrated only in
      the presence of the recombinase genes from an SCCmec element, verifying that
      SCCcap1 is a genuine SCC element but defective in mobilization. A novel
      enterotoxin gene, whose transcript was detected by Northern blotting, was found
      next to the SCCcap1 locus. We propose that the enterotoxin gene and SCCcap1 were
      inserted into this locus at the juxtaposition by independent events. Sequence
      comparison revealed numerous DNA rearrangements and mutations in SCCcap1 and the
      left flanking region, suggesting that the SCCcap1 had been inserted at the SCC
      attC site a long time ago. In addition, most genes in this region were
      incomplete, with the exception of the 15 cap1 genes, implying that the cap1 genes
      confer a survival advantage on strain M.

PMID- 12057956
TI  - Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa.
AB  - The outer carbohydrate layer, or O antigen, of Pseudomonas aeruginosa varies
      markedly in different isolates of these bacteria, and at least 20 distinct O
      antigen serotypes have been described. Previous studies have indicated that the
      major enzymes responsible for O-antigen synthesis are encoded in a cluster of
      genes that occupy a common genetic locus. We used targeted yeast recombinational
      cloning to isolate this locus from the 20 internationally recognized serotype
      strains. DNA sequencing of these isolated segments revealed that at least 11
      highly divergent gene clusters occupy this region. Homology searches of the
      encoded protein products indicated that these gene clusters are likely to direct
      O-antigen biosynthesis. The O15 serotype strains lack functional gene clusters in
      the region analyzed, suggesting that O-antigen biosynthesis genes for this
      serotype are harbored in a different portion of the genome. The overall pattern
      underscores the plasticity of the P. aeruginosa genome, in which a specific site
      in a well-conserved genomic region can be occupied by any of numerous islands of
      functionally related DNA with diverse sequences.

PMID- 12057958
TI  - Contribution of membrane-binding and enzymatic domains of penicillin binding
      protein 5 to maintenance of uniform cellular morphology of Escherichia coli.
AB  - Four low-molecular-weight penicillin binding proteins (LMW PBPs) of Escherichia
      coli are closely related and have similar DD-carboxypeptidase activities (PBPs 4,
      5, and 6 and DacD). However, only one, PBP 5, has a demonstrated physiological
      function. In its absence, certain mutants of E. coli have altered diameters and
      lose their uniform outer contour, resulting in morphologically aberrant cells. To
      determine what differentiates the activities of these LMW PBPs, we constructed
      fusion proteins combining portions of PBP 5 with fragments of other DD
      carboxypeptidases to see which hybrids restored normal morphology to a strain
      lacking PBP 5. Functional complementation occurred when truncated PBP 5 was
      combined with the terminal membrane anchor sequences of PBP 6 or DacD. However,
      complementation was not restored by the putative carboxy-terminal anchor of PBP 4
      or by a transmembrane region of the osmosensor protein ProW, even though these
      hybrids were membrane bound. Site-directed mutagenesis of the carboxy terminus of
      PBP 5 indicated that complementation required a generalized amphipathic membrane
      anchor but that no specific residues in this region seemed to be required. A
      functional fusion protein was produced by combining the N-terminal enzymatic
      domain of PBP 5 with the C-terminal beta-sheet domain of PBP 6. In contrast, the
      opposite hybrid of PBP 6 to PBP 5 was not functional. The results suggest that
      the mode of PBP 5 membrane anchoring is important, that the mechanism entails
      more than a simple mechanical tethering of the enzyme to the outer face of the
      inner membrane, and that the physiological differences among the LMW PBPs arise
      from structural differences in the DD-carboxypeptidase enzymatic core.

PMID- 12057960
TI  - An antimicrobial peptide is produced by extracellular processing of a protein
      from Propionibacterium jensenii.
AB  - A protease-activated antimicrobial peptide (PAMP) and its inactive precursor were
      purified from the culture supernatant of Propionibacterium jensenii LMG 3032 and
      characterized at the molecular level. PAMP is a 64-amino-acid cationic peptide of
      6,383 Da with physicochemical features similar to those of bacteriocins from gram
      positive bacteria. This peptide displayed bactericidal activity against several
      propionibacteria and lactobacilli. DNA sequencing indicated that the PAMP
      encoding gene (pamA) is translated as a proprotein of 198 amino acids with an N
      terminal signal peptide of 27 amino acids and that PAMP constitutes the C
      terminal part of this precursor. The amino acid sequence of pro-PAMP showed no
      similarity to those of other known proteins. By using activity tests and mass
      spectrometry, we showed that PAMP was formed upon protease treatment of the
      precursor protein. The propionibacteria produced the PAMP precursor
      constitutively during growth up to a level of approximately 4 mg/liter, but the
      producing bacteria were unable to activate the precursor. The requirement for an
      external protease represents a novel strategy for generating antimicrobial
      peptides.

PMID- 12057959
TI  - Activation of prophage eib genes for immunoglobulin-binding proteins by genes
      from the IbrAB genetic island of Escherichia coli ECOR-9.
AB  - Four distinct Escherichia coli immunoglobulin-binding (eib) genes, each of which
      encodes a surface-exposed protein that binds immunoglobulins in a nonimmune
      manner, are carried by separate prophages in E. coli reference (ECOR) strain ECOR
      9. Each eib gene was transferred to test E. coli strains, both in the form of
      multicopy recombinant plasmids and as lysogenized prophage. The derived lysogens
      express little or no Eib protein, in sharp contrast to the parental lysogen,
      suggesting that ECOR-9 has an expression-enhancing activity that the derived
      lysogens lack. Supporting this hypothesis, we cloned from ECOR-9 overlapping
      genes, ibrA and ibrB (designation is derived from "immunoglobulin-binding
      regulator"), which together activated eib expression in the derived lysogens. The
      proteins encoded by ibrA and ibrB are very similar to uncharacterized proteins
      encoded by genes of Salmonella enterica serovar Typhi and E. coli O157:H7 (in a
      prophage-like element of the Sakai strain and in two O islands of strain EDL933).
      The genomic segment containing ibrA and ibrB has been designated the IbrAB
      island. It contains regions of homology to the Shiga toxin-converting prophage,
      Stx2, as well as genes homologous to phage antirepressor genes. The left boundary
      between the IbrAB island and the chromosomal framework is located near min 35.8
      of the E. coli K-12 genome. Homology to IbrAB was found in certain other ECOR
      strains, including the other five eib-positive strains and most strains of the
      phylogenetic group B2. Sequencing of a 1.1-kb portion of ibrAB revealed that the
      other eib-positive strains diverge by </=0.1% from ECOR-9, whereas eib-negative
      ECOR-47 diverges by 16%.

PMID- 12057961
TI  - Phage TP901-1 site-specific integrase functions in human cells.
AB  - We demonstrate that the site-specific integrase encoded by phage TP901-1 of
      Lactococcus lactis subsp. cremoris has potential as a tool for engineering
      mammalian genomes. We constructed vectors that express this integrase in
      Escherichia coli and in mammalian cells and developed a simple plasmid assay to
      measure the frequency of intramolecular integration mediated by the integrase. We
      used the assay to document that the integrase functions efficiently in E. coli
      and determined that for complete reaction in E. coli, the minimal sizes of attB
      and attP are 31 and 50 bp, respectively. We carried out partial purification of
      TP901-1 integrase protein and demonstrated its functional activity in vitro in
      the absence of added cofactors, characterizing the time course and temperature
      optimum of the reaction. Finally, we showed that when expressed in human cells,
      the TP901-1 integrase carries out efficient intramolecular integration on a
      transfected plasmid substrate in the human cell environment. The TP901-1 phage
      integrase thus represents a new reagent for manipulating DNA in living mammalian
      cells.

PMID- 12057962
TI  - Multiple pathways of Spx (YjbD) proteolysis in Bacillus subtilis.
AB  - ATP-dependent proteases degrade denatured or misfolded proteins and are recruited
      for the controlled removal of proteins that block activation of regulatory
      pathways. Among the ATP-dependent proteases, those of the Clp family are
      particularly important for the growth and development of Bacillus subtilis.
      Proteolytic subunit ClpP, together with regulatory ATPase subunit ClpC or ClpX,
      is required for the normal response to stress, for development of genetic
      competence, and for sporulation. The spx (formally yjbD) gene was previously
      identified as a site of mutations that suppress defects in competence conferred
      by clpP and clpX. The level of Spx in wild-type cells grown in competence medium
      is low, and that in clpP mutants is high. This suggests that the Spx protein is a
      substrate for ClpP-containing proteases and that accumulation of Spx might be
      partly responsible for the observed pleiotropic phenotype resulting from the clpP
      mutation. In this study we examined, both in vivo and in vitro, which ClpP
      protease is responsible for degradation of Spx. Western blot analysis showed that
      Spx accumulated in clpX mutant to the same level as that observed in the clpP
      mutant. In contrast, a very low concentration of Spx was detected in a clpC
      mutant. An in vitro proteolysis experiment using purified proteins demonstrated
      that Spx was degraded by ClpCP but only in the presence of one of the ClpC
      adapter proteins, MecA or YpbH. However, ClpXP, either in the presence or in the
      absence of MecA and YpbH, was unable to degrade Spx. Transcription of spx, as
      measured by expression of spx-lacZ, was slightly increased by the clpX mutation.
      To exclude a possible effect of clpX and clpP on spx transcription, the spx gene
      was placed under the control of the IPTG (isopropyl-beta-D-thiogalactopyranoside)
      inducible Pspac promoter. In this strain, Spx accumulated when ClpX or ClpP was
      absent, suggesting that ClpX and ClpP are required for degradation of Spx. Taken
      together, these results suggest that Spx is degraded by both ClpCP and ClpXP. The
      putative proteolysis by ClpXP might require another adapter protein. Spx probably
      is degraded by ClpCP under as yet unidentified conditions. This study suggests
      that the level of Spx is tightly controlled by two different ClpP proteases.

PMID- 12057963
TI  - Genome-wide dynamic transcriptional profiling of the light-to-dark transition in
      Synechocystis sp. strain PCC 6803.
AB  - We report the results of whole-genome transcriptional profiling of the light-to
      dark transition with the model photosynthetic prokaryote Synechocystis sp. strain
      PCC 6803 (Synechocystis). Experiments were conducted by growing Synechocystis
      cultures to mid-exponential phase and then exposing them to two cycles of
      light/dark conditions, during which RNA samples were obtained. These samples were
      probed with a full-genome DNA microarray (3,169 genes, 20 samples) as well as a
      partial-genome microarray (88 genes, 29 samples). We concluded that (i) 30-min
      sampling intervals accurately captured transcriptional dynamics throughout the
      light/dark transition, (ii) 25% of the Synechocystis genes (783 genes) responded
      positively to the presence of light, and (iii) the response dynamics varied
      greatly for individual genes, with a delay of up to 120 to 150 min for some
      genes. Four classes of genes were identified on the basis of their dynamic gene
      expression profiles: class I (108 genes, 30-min response time), class II (279
      genes, 60 to 90 min), class III (258 genes, 120 to 150 min), and class IV (138
      genes, 180 min). The dynamics of several transcripts from genes involved in
      photosynthesis and primary energy generation are discussed. Finally, we applied
      Fisher discriminant analysis to better visualize the progression of the overall
      transcriptional program throughout the light/dark transition and to determine
      those genes most indicative of the lighting conditions during growth.

PMID- 12057964
TI  - Alteration of regiospecificity in biphenyl dioxygenase by active-site
      engineering.
AB  - Biphenyl dioxygenase (Bph Dox) is responsible for the initial dioxygenation step
      during the metabolism of biphenyl. The large subunit (BphA1) of Bph Dox plays a
      crucial role in the determination of the substrate specificity of biphenyl
      related compounds, including polychlorinated biphenyls (PCBs). Based on
      crystallographic analyses of naphthalene dioxygenase (B. Kauppi, K. Lee, E.
      Carredano, R. E. Parales, D. T. Gibson, H. Eklund, and S. Ramaswamy, Structure
      6:571-586, 1998), we developed a three-dimensional model of KF707 BphA1 of
      Pseudomonas pseudoalcaligenes KF707. Based on structural information about the
      amino acids which coordinate the catalytic nonheme iron center, we constructed 12
      site-directed BphA1 mutants with changes at positions 227, 332, 335, 376, 377,
      and 383 and expressed these enzymes in Escherichia coli. The Ile335Phe,
      Thr376Asn, and Phe377Leu Bph Dox mutants exhibited altered regiospecificities for
      various PCBs compared with wild-type Bph Dox. In particular, the Ile335Phe mutant
      acquired the ability to degrade 2,5,2',5'-tetrachlorobiphenyl by 3,4
      dioxygenation and showed bifunctional 2,3-dioxygenase and 3,4-dioxygenase
      activities for 2,5,2'-trichlorobiphenyl and 2,5,4'-trichlorobiphenyl.
      Furthermore, two mutants, the Phe227Val and Phe377Ala mutants, introduced
      molecular oxygen at the 2,3 position, forming 3-chloro-2',3'-dihydroxy biphenyl
      with concomitant dechlorination.

PMID- 12057965
TI  - A membrane-bound archaeal Lon protease displays ATP-independent proteolytic
      activity towards unfolded proteins and ATP-dependent activity for folded
      proteins.
AB  - In contrast to the eucaryal 26S proteasome and the bacterial ATP-dependent
      proteases, little is known about the energy-dependent proteolysis in members of
      the third domain, Archae. We cloned a gene homologous to ATP-dependent Lon
      protease from a hyperthermophilic archaeon and observed the unique properties of
      the archaeal Lon. Lon from Thermococcus kodakaraensis KOD1 (Lon(Tk)) is a 70-kDa
      protein with an N-terminal ATPase domain belonging to the AAA(+) superfamily and
      a C-terminal protease domain including a putative catalytic triad. Interestingly,
      a secondary structure prediction suggested the presence of two transmembrane
      helices within the ATPase domain and Western blot analysis using specific
      antiserum against the recombinant protein clearly indicated that Lon(Tk) was
      actually a membrane-bound protein. The recombinant Lon(Tk) possessed thermostable
      ATPase activity and peptide cleavage activity toward fluorogenic peptides with
      optimum temperatures of 95 and 70 degrees C, respectively. Unlike the enzyme from
      Escherichia coli, we found that Lon(Tk) showed higher peptide cleavage activity
      in the absence of ATP than it did in the presence of ATP. When three kinds of
      proteins with different thermostabilities were examined as substrates, it was
      found that Lon(Tk) required ATP for degradation of folded proteins, probably due
      to a chaperone-like function of the ATPase domain, along with ATP hydrolysis. In
      contrast, Lon(Tk) degraded unfolded proteins in an ATP-independent manner,
      suggesting a mode of action in Lon(Tk) different from that of its bacterial
      counterpart.

PMID- 12057966
TI  - Toxic waste disposal in Escherichia coli.
AB  - About 10% of the nalidixic acid-resistant (Nal(r)) mutants in a transposition
      induced library exhibited a growth factor requirement as the result of cysH,
      icdA, metE, or purB mutation. Resistance in all of these mutants required a
      functional AcrAB-TolC efflux pump, but the EmrAB-TolC pump played no obvious
      role. Transcription of acrAB was increased in each type of Nal(r) mutant. In the
      icdA and purB mutants, each of the known signaling pathways appeared to be used
      in activating the AcrAB-TolC pump. The metabolites that accumulate upstream of
      the blocks caused by the mutations are hypothesized to increase the levels of the
      AcrAB-TolC pump, thereby removing nalidixic acid from the organism.

PMID- 12057967
TI  - Functional interaction of region 4 of the extracytoplasmic function sigma factor
      FecI with the cytoplasmic portion of the FecR transmembrane protein of the
      Escherichia coli ferric citrate transport system.
AB  - Transcriptional regulation of the ferric citrate transport genes of Escherichia
      coli is initiated by the binding of ferric citrate to the outer membrane protein
      FecA. This binding elicits a signal that is transmitted by FecR across the
      cytoplasmic membrane into the cytoplasm, where the sigma factor FecI directs the
      RNA polymerase to the promoter upstream of the fecABCDE genes. An in vivo
      deletion analysis using a bacterial two-hybrid system assigned the interaction of
      the FecR and FecI proteins to the cytoplasmic portion of the FecR transmembrane
      protein and region 4 of FecI. Missense mutations randomly generated by PCR were
      localized to region 4 of FecI, and the mutants were impaired with regard to the
      interaction of FecR with FecI and fecB-lacZ transcription. The cloned region 4 of
      FecI interfered with fecB-lacZ transcription. Interaction of N-proximal regions
      of predicted FecR homologs with region 4 of predicted FecI homologs of
      Pseudomonas aeruginosa was demonstrated. The interaction was specific in that
      only cognate protein pairs interacted with each other; no interactions occurred
      between heterologous combinations of the P. aeruginosa proteins and between a P.
      aeruginosa FecI homolog and E. coli FecR. The results demonstrate that region 4
      of FecI specifically binds FecR and that this binding is necessary for FecI to
      function as a sigma factor.

PMID- 12057968
TI  - Variable surface protein Vmm of Mycoplasma mycoides subsp. mycoides small colony
      type.
AB  - A variable surface protein, Vmm, of the bovine pathogen Mycoplasma mycoides
      subsp. mycoides small colony type (M. mycoides SC) has been identified and
      characterized. Vmm was specific for the SC biotype and was expressed by 68 of 69
      analyzed M. mycoides SC strains. The protein was found to undergo reversible
      phase variation at a frequency of 9 x 10(-4) to 5 x 10(-5) per cell per
      generation. The vmm gene was present in all of the 69 tested M. mycoides SC
      strains and encodes a lipoprotein precursor of 59 amino acids (aa), where the
      mature protein was predicted to be 36 aa and was anchored to the membrane by only
      the lipid moiety, as no transmembrane region could be identified. DNA sequencing
      of the vmm gene region from ON and OFF clones showed that the expression of Vmm
      was regulated at the transcriptional level by dinucleotide insertions or
      deletions in a repetitive region of the promoter spacer. Vmm-like genes were also
      found in four closely related mycoplasmas, Mycoplasma capricolum subsp.
      capricolum, M. capricolum subsp. capripneumoniae, Mycoplasma sp. bovine serogroup
      7, and Mycoplasma putrefaciens. However, Vmm could not be detected in whole-cell
      lysates of these species, suggesting that the proteins encoded by the vmm-like
      genes lack the binding epitope for the monoclonal antibody used in this study or,
      alternatively, that the Vmm-like proteins were not expressed.

PMID- 12057970
TI  - Transcriptional response of Pasteurella multocida to nutrient limitation.
AB  - Bacteria often encounter environments where nutrient availability is limited, and
      they must adapt accordingly. To identify Pasteurella multocida genes that are
      differentially expressed during nutrient limitation, we utilized whole-genome
      microarrays to compare levels of gene expression during growth in rich and
      minimal media. Our analysis showed that the levels of expression of a total of
      669 genes, representing approximately one-third of the genome, were detectably
      altered over the course of the experiment. A large number (n = 439) of genes,
      including those involved in energy metabolism, transport, protein synthesis, and
      binding, were expressed at higher levels in rich medium, suggesting that, upon
      exposure to a rich environment, P. multocida immediately begins to turn on many
      energy-intensive biosynthetic pathways or, conversely, turns these genes off when
      it is exposed to a nutrient-deficient environment. Genes with increased
      expression in minimal medium (n = 230) included those encoding amino acid
      biosynthesis and transport systems, outer membrane proteins, and heat shock
      proteins. Importantly, our analysis also identified a large number (n = 164) of
      genes with unknown functions whose expression was altered during nutrient
      limitation. Overall, the results of our study show that a wide repertoire of
      genes, many of which have yet to be functionally classified, undergo
      transcriptional regulation in P. multocida in response to growth in minimal
      medium and provide a strong foundation to investigate the transcriptional
      response of this multispecies pathogen to growth in a nutrient-limited
      environment.

PMID- 12057969
TI  - Assembly of colicin A in the outer membrane of producing Escherichia coli cells
      requires both phospholipase A and one porin, but phospholipase A is sufficient
      for secretion.
AB  - Three oligomeric forms of colicin A with apparent molecular masses of about 95 to
      98 kDa were detected on sodium dodecyl sulfate (SDS)-polyacrylamide gels loaded
      with unheated samples from colicin A-producing cells of Escherichia coli. These
      heat-labile forms, called colicins Au, were visualized both on immunoblots probed
      with monoclonal antibodies against colicin A and by radiolabeling. Cell
      fractionation studies show that these forms of colicin A were localized in the
      outer membrane whether or not the producing cells contained the cal gene, which
      encodes the colicin A lysis protein responsible for colicin A release in the
      medium. Pulse-chase experiments indicated that their assembly into the outer
      membrane, as measured by their heat modifiable migration in SDS gels, was an
      efficient process. Colicins Au were produced in various null mutant strains, each
      devoid of one major outer membrane protein, except in a mutant devoid of both
      OmpC and OmpF porins. In cells devoid of outer membrane phospholipase A (OMPLA),
      colicin A was not expressed. Colicins Au were detected on immunoblots of induced
      cells probed with either polyclonal antibodies to OmpF or monoclonal antibodies
      to OMPLA, indicating that they were associated with both OmpF and OMPLA. Similar
      heat-labile forms were obtained with various colicin A derivatives, demonstrating
      that the C-terminal domain of colicin A, but not the hydrophobic hairpin present
      in this domain, was involved in their formation.

PMID- 12057972
TI  - PII T-loop mutations affecting signal transduction to NtrB also abolish yeast two
      hybrid interactions.
AB  - Mutations A49P and Delta47-53 at the T loop of the Escherichia coli GlnB (PII)
      protein impair regulatory interactions with the two-component sensor regulator
      NtrB (P. Jiang, P. Zucker, M. R. Atkinson, E. S. Kamberov, W. Tirasophon, P.
      Chandran, B. R. Schepke, and A. J. Ninfa, J. Bacteriol. 179: 4342-4353, 1997). We
      show here that these mutations also impair interactions between PII and NtrB in
      the yeast two-hybrid system, indicating that defects in NtrB regulation closely
      reflect binding impairment. The reported results underline the strength of two
      hybrid assays for analysis of interactions involving the T loop of PII proteins.

PMID- 12057971
TI  - Yop fusions to tightly folded protein domains and their effects on Yersinia
      enterocolitica type III secretion.
AB  - Yersinia enterocolitica organisms secrete Yop proteins via the type III pathway.
      Translational fusion of yop genes to ubiquitin or dihydrofolate reductase results
      in hybrid proteins that cannot be secreted. The folding of hybrids prevents their
      own transport, but it does not hinder the type III secretion of other Yops.

PMID- 12057973
TI  - Penicillin-binding proteins 1a and 1b form independent dimers in Escherichia
      coli.
AB  - We report here that PBP1a can dimerize but does not interact with PBP1b to form
      PBP1a/PBP1b heterodimers in Escherichia coli. These findings support the idea of
      a relevant involvement of dimerization of both PBP1a and PBP1b during murein
      synthesis and suggest the existence of different peptidoglycan synthesis
      complexes.

PMID- 12057974
TI  - Phage lambda red-mediated adaptive mutation.
AB  - Replacement of the recBCD genes of Escherichia coli with the red recombination
      genes of bacteriophage lambda results in a strain in which adaptive mutation
      occurs at an elevated frequency. Like RecBCD-dependent adaptive mutation, Red
      mediated adaptive mutation is dependent upon recA and ruvABC functions.

PMID- 12057975
TI  - Pyridoxal 5-phosphate inhibition of substrate selectivity mutants of UhpT, the
      sugar 6-phosphate carrier of Escherichia coli.
AB  - In the sugar phosphate transporter UhpT, gain-of-function derivatives that prefer
      phosphoenolpyruvate (PEP) as substrate have an uncompensated lysine residue on
      transmembrane segment 11. We show here that these variants are also highly
      susceptible to substrate-protectable inhibition by covalent modification of
      lysine with pyridoxal 5-phosphate. The chemical requirements of this interaction
      provide evidence that the gain-of-function phenotype results from the pairing of
      the uncompensated lysines in these mutants with the anionic carboxyl group of
      PEP.

PMID- 12057976
TI  - The enigmatic Escherichia coli fadE gene is yafH.
AB  - The identity of the gene encoding acyl coenzyme A dehydrogenase is a major
      remaining mystery of the Escherichia coli fatty acid degradation (fad) regulon.
      Our prior genome array analyses showed that transcription of the yafH gene is
      controlled by the FadR regulatory protein. We now report direct experimental
      proof that yafH and fadE are the same gene.

PMID- 12057978
TI  - Obesity, metabolic syndrome, and coronary atherosclerosis.

PMID- 12057979
TI  - Intracoronary brachytherapy: past, present, and future.

PMID- 12057980
TI  - Evolution of the study of left ventricular function: everything old is new again.

PMID- 12057981
TI  - Management of the patient who has been resuscitated from sudden cardiac death.

PMID- 12057982
TI  - Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose
      positron emission tomography.
AB  - BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of
      inflammatory cell activity within the plaque. Current imaging techniques provide
      anatomic data but no indication of plaque inflammation. The glucose analogue
      [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity
      non-invasively by PET. In this study we tested whether 18FDG-PET imaging can
      identify inflammation within carotid artery atherosclerotic plaques. METHODS AND
      RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged
      using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in
      18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG
      accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher
      than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake
      into normal carotid arteries. Autoradiography of excised plaques confirmed
      accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS:
      This study demonstrates that atherosclerotic plaque inflammation can be imaged
      with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than
      asymptomatic lesions.

PMID- 12057983
TI  - Obesity accelerates the progression of coronary atherosclerosis in young men.
AB  - BACKGROUND: Obesity is a risk factor for adult coronary heart disease and is
      increasing in prevalence among youths as well as adults. Results regarding the
      association of obesity with atherosclerosis are conflicting, particularly when
      analyses account for other risk factors. METHODS AND RESULTS: The Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood,
      and other tissue from approximately 3000 persons aged 15 to 34 years dying of
      external causes and autopsied in forensic laboratories. We measured gross
      atherosclerotic lesions in the right coronary artery (RCA), American Heart
      Association (AHA) lesion grade in the left anterior descending coronary artery
      (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal
      thickness of renal arteries (for hypertension), glycohemoglobin (for
      hyperglycemia), and adiposity by body mass index (BMI) and thickness of the
      panniculus adiposus. BMI in young men was associated with both fatty streaks and
      raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect
      of obesity (BMI>30 kg/m(2)) on RCA raised lesions was greater in young men with a
      thick panniculus adiposus. Obesity was associated with non-HDL and HDL
      (inversely) cholesterol concentrations, smoking (inversely), hypertension, and
      glycohemoglobin concentration, and these variables accounted for approximately
      15% of the effect of obesity on coronary atherosclerosis in young men. BMI was
      not associated with coronary atherosclerosis in young women although there was
      trend among those with a thick panniculus adiposus. CONCLUSIONS: Obesity is
      associated with accelerated coronary atherosclerosis in adolescent and young
      adult men. These observations support the current emphasis on controlling obesity
      to prevent adult coronary heart disease.

PMID- 12057984
TI  - Conversion from vagal to sympathetic predominance with strenuous training in high
      performance world class athletes.
AB  - BACKGROUND: Benefits of moderate endurance training include increases in
      parasympathetic activity and baroreflex sensitivity (BRS) and a relative decrease
      in sympathetic tone. However, the effect of very intensive training load on
      neural cardiovascular regulation is not known. We tested the hypothesis that
      strenuous endurance training, like in high-performance athletes, would enhance
      sympathetic activation and reduce vagal inhibition. METHODS AND RESULTS: We
      studied the entire Italian junior national team of rowing (n=7) at increasing
      training loads up to 75% and 100% of maximum, the latter approximately 20 days
      before the Rowing World Championship. Autoregressive power spectral analysis was
      used to investigate RR interval and blood pressure (BP) variabilities. BRS was
      assessed by the sequences method. Increasing training load up to 75% of maximum
      was associated with a progressive resting bradycardia and increased indexes of
      cardiac vagal modulation and BRS. However, at 100% training load these effects
      were reversed, with increases in resting heart rate, diastolic BP, low-frequency
      RR interval, and BP variabilities and decreases in high-frequency RR variability
      and BRS. Three athletes later won medals in the World Championship. CONCLUSIONS:
      This study indicates that very intensive endurance training shifted the
      cardiovascular autonomic modulation from a parasympathetic toward a sympathetic
      predominance. This finding should be interpreted within the context of the
      substantial role played by the sympathetic nervous system in increasing
      cardiovascular performance at peak training. Whether the altered BP and autonomic
      function shown in this study might be in time hazardous to human cardiovascular
      system remains to be established.

PMID- 12057985
TI  - Plasma homocysteine and parental myocardial infarction in young adults in
      Jerusalem.
AB  - BACKGROUND: A causal role for mildly elevated plasma homocysteine (tHcy) in
      cardiovascular disease remains undetermined. To address the unresolved issue of
      the antecedent-consequent directionality of the relationship, we assessed the
      familial association of tHcy with parental myocardial infarction (MI) in young
      Israeli men and women. We also compared tHcy concentrations in Jerusalem, where
      rates of coronary heart disease (CHD) are high, with the United States Third
      National Health and Examination Survey (NHANES III). METHODS AND RESULTS: A total
      of 8646 17-year-olds and 6952 parents were examined from 1976 to 1979 in
      Jerusalem. At ages 28 to 32 years, offspring of parents who experienced a
      documented MI during a 10-year follow-up (n=133 men, 62 women; 72% response) and
      offspring of CHD-free parents (n=389 men, 208 women; 71% response) were
      reexamined. tHcy levels were determined by the same laboratory for the NHANES non
      Hispanic white population aged 25 to 34 years (n=379) and the Jerusalem
      population sample (n=858). Men from Jerusalem, but not women, had clearly higher
      tHcy levels than the sample from the United States (90th percentile, 23 versus 14
      micromol/L). This difference was largely attributable to lower plasma vitamin B12
      levels in the Israeli population. Male case offspring had higher adjusted tHcy
      than did controls (1.9 micromol/L, P=0.002). Logistic modeling revealed a graded
      increase in risk of parental MI across quintiles of offspring tHcy, with an
      adjusted odds ratio of 2.7 in the 5th quintile (P=0.0026 for trend). CONCLUSIONS:
      The higher tHcy in young male offspring of parents with CHD suggests that
      elevated tHcy precedes manifestation of CHD. The elevated population tHcy in men
      may contribute to the high incidence of CHD in Israel.

PMID- 12057986
TI  - Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among
      diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban
      and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up.
AB  - BACKGROUND: The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab, a
      monoclonal antibody, has been shown to improve early and late outcomes among
      diabetic patients undergoing percutaneous coronary intervention (PCI). It is
      unknown whether small-molecule agents confer similar benefits. METHODS AND
      RESULTS: In 18 countries, 4809 patients undergoing PCI with stent implantation
      were randomized to tirofiban or abciximab. At the time of enrollment, patients
      were stratified according to diabetes status. As compared with non-diabetic
      patients, patients with diabetes (n=1117) showed similar 30-day ischemic
      outcomes, an increased incidence of any target vessel revascularization (TVR) at
      6 months (10.3% versus 7.8%; P= 0.008), and a trend toward higher 1-year
      mortality (2.5% versus 1.6%; P=0.056). Among diabetic patients randomized to
      tirofiban (n=560), the incidence of death, myocardial infarction (MI), or urgent
      TVR at 30 days was 6.2%, and among those randomized to abciximab (n=557) it was
      5.4% (hazard ratio [HR] 1.16; P=0.540). At 6 months, the composite of death, MI,
      or any TVR occurred in 15.7% and in 16.9% of tirofiban and abciximab patients,
      respectively (HR 0.93; P=0.610). Any TVR occurred in 9.5% and 11.1%, respectively
      (HR 0.84; P= 0.366). The 1-year mortality was 2.1% in the tirofiban group and
      2.9% in the abciximab group (HR 0.74; P= 0.436). CONCLUSIONS: Among diabetic
      patients undergoing PCI, tirofiban and abciximab were associated with comparable
      event rates, including similar rates of 6-month TVR and 1-year mortality. These
      findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do
      not translate into a discernible long-term clinical benefit among diabetic
      patients.

PMID- 12057988
TI  - Mechanism of syncope in patients with heart disease and negative
      electrophysiologic test.
AB  - BACKGROUND: In patients with syncope and structural heart disease, syncope is
      suspected to be attributable to a primary cardiac arrhythmia, but little is known
      of its mechanism when electrophysiologic study is unremarkable. METHODS AND
      RESULTS: We applied an implantable loop recorder in 35 patients with overt heart
      disease at risk of ventricular arrhythmia, because these were patients with
      previous myocardial infarction or cardiomyopathy with depressed ejection fraction
      or nonsustained ventricular tachycardia in whom an electrophysiologic study was
      unremarkable. During a follow-up of 3 to 15 months, syncope recurred in 6
      patients (17%) after a mean of 6+/-5 months; in 3 patients, the mechanism of
      syncope was bradycardia with long pauses (sudden-onset AV block in 2 cases and
      sinus arrest in 1 case); in 1 patient, there was stable sinus tachycardia; and in
      2 patients, who had chronic atrial fibrillation, there was an increase in
      ventricular rate. A total of 23 episodes of presyncope were documented in 8
      patients (23%): no rhythm variation or mild tachycardia in 12 cases, paroxysmal
      atrial fibrillation or atrial tachycardia in 10 cases, and sustained ventricular
      tachycardia in 1 case. No patient died during the study period nor suffered from
      injury attributable to syncopal relapse. CONCLUSIONS: The patients with
      unexplained syncope, structural heart disease, and negative electrophysiologic
      study had a favorable medium-term outcome with no case of death and a low
      recurrence rate of syncope without related injury. The mechanism of syncope was
      heterogeneous, and ventricular tachyarrhythmia was unlikely.

PMID- 12057987
TI  - Five-year clinical follow-up after intracoronary radiation: results of a
      randomized clinical trial.
AB  - BACKGROUND: Several clinical trials indicate that intracoronary radiation is safe
      and effective for treatment of restenotic coronary arteries. We previously
      reported 6-month and 3-year clinical and angiographic follow-up demonstrating
      significant decreases in target lesion revascularization (TLR) and angiographic
      restenosis after gamma radiation of restenotic lesions. The objective of this
      study was to document the clinical outcome 5 years after treatment of restenotic
      coronary arteries with catheter-based iridium-192 (192Ir). METHODS AND RESULTS: A
      double-blind, randomized trail compared 192Ir to placebo sources in patients with
      restenosis after coronary angioplasty. Over a 9-month period, 55 patients were
      enrolled; 26 were randomized to 192Ir and 29 to placebo. At 5-year follow-up, TLR
      was significantly lower in the 192Ir group (23.1% versus 48.3%; P=0.05). There
      were 2 TLRs between years 3 and 5 in patients in the 192Ir group and none in
      patients in the placebo group. The 5-year event-free survival rate (freedom from
      death, myocardial infarction, or TLR) was greater in 192Ir-treated patients
      (61.5% versus 34.5%; P=0.02). CONCLUSIONS: Despite apparent mitigation of
      efficacy over time, there remains a significant reduction in TLR at 5 years and
      an improvement in event-free survival in patients treated with intracoronary
      192Ir. The early clinical benefits after intracoronary gamma radiation with 192Ir
      seem durable at 5-year clinical follow-up.

PMID- 12057989
TI  - Internal cardioversion of chronic atrial fibrillation during percutaneous mitral
      commissurotomy: insight into reversal of chronic stretch-induced atrial
      remodeling.
AB  - BACKGROUND: Mechanoelectrical feedback caused by atrial dilatation plays an
      important role in atrial fibrillation (AF). To test the hypothesis that
      remodeling is reversible by reducing atrial stretch, we investigated
      electrophysiological changes after a reduction of left atrial (LA) pressure in
      patients undergoing percutaneous balloon mitral commissurotomy (PBMC). METHODS
      AND RESULTS: In 22 patients with chronic AF who were undergoing PBMC for mitral
      stenosis, internal cardioversion was successful in 19 patients (86%). Twelve
      patients with sinus rhythm acted as controls. Mean LA pressure was significantly
      reduced after PBMC (18.5+/-5.9 mm Hg versus 10.2+/-4.1 mm Hg; P<0.001). The
      effective refractory period (ERP), conduction delay (CD), and the index of
      heterogeneity (CoV) of the ERP and CD were compared. Changes in LA pressure were
      only significantly correlated with AF vulnerability (r=0.7; P=0.02) and CoV of CD
      (r=0.3; P=0.03). There were no significant changes in ERP and CD immediately
      after PBMC in the AF group. However, the overall CoV of ERP was reduced in the AF
      group after PBMC. There were homogenous, although not significant, increases in
      regional ERP in the control group immediately after PBMC. Atrial CD and CoV of CD
      were significantly reduced after PBMC in the control group; this was most
      prominent within the regions of the LA. CONCLUSIONS: AF vulnerability and CoV of
      CD correlated significantly with LA pressure. A homogenous increase in regional
      ERPs could be demonstrated in the control group after an immediate reduction of
      atrial stretch, whereas the recovery course of electrical remodeling was
      prolonged and heterogenous in the AF group. Regional conductions were
      irreversible in patients with preexisting AF.

PMID- 12057990
TI  - Autonomic tone variations before the onset of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Mechanisms favoring the occurrence of paroxysmal atrial fibrillation
      (PAF) are complex and poorly defined. This study was designed to analyze dynamic
      changes in autonomic tone preceding the onset of PAF in a large group of
      patients. METHODS AND RESULTS: Holter tapes from 77 unselected consecutive
      patients (63 men and 14 women aged 58+/-12 years) with PAF were analyzed. A total
      of 147 episodes of sustained AF (>30 minutes) were recorded and submitted to time
      domain and frequency-domain heart rate variability analyses; 6 periods were
      studied using repeated measures ANOVA: the 24-hour period, the hour preceding
      PAF, and the 20 minutes before PAF divided into four 5-minute periods. In the
      time-domain analyses, a linear decrease in mean RR interval from 925+/-16 to
      906+/-16 ms (P<0.0002) was observed before the onset of PAF, together with a
      significant increase in the standard deviation of NN intervals from 65+/-4 to
      70+/-4 ms (P<0.02). In the frequency-domain analyses, a significant increase in
      high-frequency (HF, HF-NU) components was observed before PAF (P<0.001 and
      P<0.0001, respectively), together with a progressive decrease in low-frequency
      components (LF, LF-NU) (P<0.0001 and P<0.004, respectively). The low/high
      frequency ratio showed a linear increase until 10 minutes before PAF, followed by
      a sharp decrease immediately before PAF, suggesting a primary increase in
      adrenergic tone followed by a marked modulation toward vagal predominance. No
      difference was observed in these heart rate variability changes between patients
      with "lone" PAF and patients with structural heart disease. CONCLUSIONS: The
      occurrence of PAF greatly depends on variations of the autonomic tone, with a
      primary increase in adrenergic tone followed by an abrupt shift toward vagal
      predominance.

PMID- 12057991
TI  - Obligatory role of cyclic adenosine monophosphate response element in
      cyclooxygenase-2 promoter induction and feedback regulation by inflammatory
      mediators.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) plays a key role in human inflammatory
      disorders such as vascular inflammation. COX-2 promoter activity is induced by
      proinflammatory mediators, but the role of cyclic adenosine monophosphate
      response element (CRE) in promoter stimulation remains unclear. METHODS AND
      RESULTS: Transient transfection of a 0.9-kb COX-2 promoter fragment bearing CRE
      mutation abrogated COX-2 promoter activity induced by proinflammatory mediators
      in human endothelial cells and fibroblasts. Dual mutations of CRE and an upstream
      CCAAT/enhancer binding protein (C/EBP) site did not have an additional effect.
      Binding of CREB-2, ATF-2, USF-2, and c-Jun transactivators to a wild-type and CRE
      mutated oligonucleotide was analyzed by a novel DNA-binding assay. CREB-2 and ATF
      2 in nuclear extracts of unstimulated endothelial cells bound to CRE, whereas USF
      2 and c-Jun or c-Fos bound to non-CRE sites. CREB-2 and c-Fos binding was
      increased by phorbol 12-myristate 13-acetate but not tumor necrosis factor-alpha.
      The binding assay and chromatin immunoprecipitation revealed binding of P300
      coactivator to the COX-2 promoter region. CONCLUSIONS: CRE plays an obligatory
      role in COX-2 promoter activation by diverse stimuli. CREB-2 and ATF-2 bound to
      CRE serve as an anchor for P300 interaction with upstream transactivators and
      downstream transcription machinery.

PMID- 12057992
TI  - In vivo imaging of proteolytic activity in atherosclerosis.
AB  - BACKGROUND: Atherosclerotic plaque rupture, the most important cause of acute
      cardiovascular incidents, has been strongly associated with vascular
      inflammation. On the basis of the hypothesis that the inflammatory response and
      proteolysis lead to plaque rupture, we have examined the role of cathepsin B as a
      model proteolytic enzyme. METHODS AND RESULTS: Using western-type diet-fed apoE
      and apoE/endothelial NO synthase double knockout mice as models of
      atherosclerosis, we show (1) that cathepsin B is upregulated in atherosclerotic
      lesions characterized by high degrees of inflammation compared with normal aorta
      or silent lesions, (2) that intravenously injectable novel cathepsin B imaging
      beacons are highly activated within active atherosclerotic lesions and colocalize
      with cathepsin B immunoreactivity, and (3) that cathepsin B activity in
      atherosclerotic lesions can be imaged in whole animals by using a novel near
      infrared tomographic imaging system. CONCLUSIONS: These studies indicate that
      cathepsin B, and potentially other proteases, may serve as a biomarker for
      vulnerable plaques when probed with beacons. The tomographic in vivo imaging
      method as well as catheter-based optical sensing methods could be readily adapted
      to screening and potentially to the molecular profiling of a number of proteases
      in vulnerable plaque in vivo.

PMID- 12057994
TI  - Augmentation of intrapericardial nitric oxide level by a prolonged-release nitric
      oxide donor reduces luminal narrowing after porcine coronary angioplasty.
AB  - BACKGROUND: Nitric oxide (NO) is a potent vasodilator and antiplatelet agent that
      suppresses vascular smooth muscle cell proliferation. Hypothesizing that
      generating NO in the pericardial space would reduce luminal narrowing after
      coronary angioplasty without affecting systemic hemodynamics, we have determined
      the effect of a novel NO donor on vascular healing after balloon overstretch.
      METHODS AND RESULTS: Diazeniumdiolated bovine serum albumin (D-BSA; molecular
      weight 74 kDa, half-life for NO release 20 days) was radioiodinated and found by
      intravital gamma-imaging to have a longer residence time in pig pericardium than
      a low-molecular-weight (0.5 kDa) analogue (22 versus 4.6 hours, respectively).
      Intrapericardial injection of D-BSA immediately before 30% overstretch of normal
      left anterior descending and left circumflex coronary arteries dose dependently
      reduced the intimal/medial area ratio by up to 50% relative to controls treated
      with underivatized albumin when measured 2 weeks after intervention. Positive
      remodeling was also noted, which increased luminal area relative to control.
      CONCLUSIONS: Perivascular exposure of coronary arteries to NO via
      intrapericardial D-BSA administration reduced flow-restricting lesion development
      after angioplasty in pigs without causing significant systemic effects. The data
      suggest that intrapericardial delivery of NO donors for which NO release rates
      and pericardial residence times are matched and optimized might be a beneficial
      adjunct to coronary angioplasty.

PMID- 12057996
TI  - Hypoxia induces aortic hypertrophic growth, left ventricular dysfunction, and
      sympathetic hyperinnervation of peripheral arteries in the chick embryo.
AB  - BACKGROUND: Low birth weight is associated with an increased incidence of
      cardiovascular diseases, including hypertension, later in life. This suggests
      that antenatal insults program for fetal adaptations of the circulatory system.
      In the present study, we evaluated the effects of mild hypoxia on cardiac
      function, blood pressure control, and arterial structure and function in near
      term chick embryos. METHODS AND RESULTS: Chick embryos were incubated under
      normoxic (21% O2) or hypoxic (15% O2) conditions and evaluated at incubation day
      19 by use of histological techniques, isolated heart preparations, and in vivo
      measurements of sympathetic arterial tone and systemic hemodynamics. Chronic
      hypoxia caused a 33% increase in mortality and an 11% reduction in body weight in
      surviving embryos. The lumen of the ascending aorta in hypoxic embryos was 23%
      smaller. Left ventricular systolic pressure was 22% lower, and heart weight/body
      weight ratio was 14% higher. In resistance arteries of hypoxic embryos, in vivo
      baseline tone was 23% higher, norepinephrine sensitivity was similar, and
      norepinephrine release from sympathetic nerves increased 2-fold, indicating
      sympathetic hyperinnervation. Mean arterial pressure and heart rate were similar
      under resting conditions, but chronically hypoxic embryos failed to maintain
      blood pressure during acute stress. CONCLUSIONS: This study indicates that mild
      hypoxia during embryonic development induces alterations in cardiac and vascular
      function and structure and affects hemodynamic regulation. These findings reveal
      that antenatal insults have profound effects on the control and design of the
      circulatory system that are already established at birth and may program for
      hypertension and heart failure at a later age.

PMID- 12057993
TI  - Left ventricular thrombus enhancement after intravenous injection of echogenic
      immunoliposomes: studies in a new experimental model.
AB  - BACKGROUND: Targeted echogenic immunoliposomes (ELIPs) for ultrasound enhancement
      of atheroma components have been developed. To date, ELIP delivery has been intra
      arterial. To determine whether ELIPs can be given intravenously with enhancement
      of systemic structures, a left ventricular thrombus (LVT) model was developed.
      METHODS AND RESULTS: In 6 animals plus 1 dose-ranging animal, the apical coronary
      arteries were ligated, and an LVT was produced by injecting Hemaseel fibrin
      adhesive through the apical myocardium. The thrombus was imaged epicardially and
      transthoracically at 0, 1, 5, and 10 minutes after anti-fibrinogen ELIP
      injections. The dose of ELIPs was varied. PBS and unconjugated ELIPs were
      controls. The apical thrombi were easily reproduced and clearly visible with
      epicardial and transthoracic ultrasound. Enhancement occurred with 2 mg anti
      fibrinogen ELIPs and increased with dose. With 8 mg ELIPs, enhancement was
      different from control within 10 minutes (P<0.05). Rhodamine-labeled anti
      fibrinogen ELIPs were seen with fluorescence microscopy of the LVT. Blinded
      viewing detected enhancement by 10 minutes in all animals after anti-fibrinogen
      ELIPs. CONCLUSIONS: We describe an easily reproducible LVT model. Anti-fibrinogen
      ELIPs delivered intravenously, as a single-step process, rapidly enhance the
      ultrasound image of a systemic target. This allows for future development of
      ELIPs as a targeted ultrasound contrast agent.

PMID- 12057995
TI  - Angiotensin-converting enzyme inhibitors improve coronary flow reserve in dilated
      cardiomyopathy by a bradykinin-mediated, nitric oxide-dependent mechanism.
AB  - BACKGROUND: ACE inhibitors have been used extensively in heart failure, where
      they induce systemic vasodilatation. ACE inhibitors have also been shown to
      reduce ischemic events after myocardial infarction, although their mechanisms of
      action on the coronary circulation are less well understood. The purpose of the
      present study was to determine the effects and the mechanism of action of the ACE
      inhibitor enalaprilat and the AT1 antagonist losartan on regional myocardial
      perfusion and coronary flow and vasodilator reserve in conscious dogs with pacing
      induced dilated cardiomyopathy (DCM). METHODS AND RESULTS: Twenty-seven
      conscious, chronically instrumented dogs were studied during advanced stages of
      dilated cardiomyopathy, which was induced by rapid pacing. Enalaprilat (1.25 mg
      IV) improved transmural distribution (endocardial/epicardial ratio) at rest
      (baseline, 0.91+/-0.11; enalaprilat, 1.02+/-0.07 mL/min per g; P<0.05) and during
      atrial pacing (baseline, 0.82+/-0.11; enalaprilat, 0.98+/-0.07; P<0.05).
      Enalaprilat also restored subendocardial coronary flow reserve (CFR) (baseline
      CFR, 1.89+/-0.11; enalaprilat CFR, 2.74+/-0.33; P<0.05) in DCM. These effects
      were abolished by pretreatment with the NO synthase inhibitor nitro-L-arginine.
      The effects were recapitulated by the bradykinin(2) receptor agonist cereport but
      not by the AT1 antagonist losartan. CONCLUSIONS: The ACE inhibitor enalaprilat
      improves transmural myocardial perfusion at rest and after chronotropic stress
      and restores impaired subendocardial coronary flow and vasodilator reserve in
      DCM. The effects of enalaprilat were bradykinin mediated and NO dependent and
      were not recapitulated by losartan. These data suggest beneficial effects of ACE
      inhibitors on the coronary circulation in DCM that are not shared by AT1 receptor
      antagonists.

PMID- 12057998
TI  - Fat substitutes and health: an advisory from the Nutrition Committee of the
      American Heart Association.

PMID- 12057997
TI  - Images in cardiovascular medicine. Incessant ventricular tachycardia in an infant
      treated with transmural radiofrequency ablation.

PMID- 12058000
TI  - New concepts in hypertrophic cardiomyopathies.

PMID- 12058001
TI  - Looking for diastolic dysfunction.

PMID- 12057999
TI  - Images in cardiovascular medicine. Focal in-stent restenosis near step-up: roles
      of low and oscillating shear stress?

PMID- 12058002
TI  - Giant left atrium associated with mitral valve prolapse.

PMID- 12058003
TI  - Emergency department and hospital preventive care of elderly next of kin of
      victims of sudden cardiac death and fatal acute myocardial infarction.

PMID- 12058005
TI  - A developmental perspective on adolescent health and illness: an introduction to
      the special issues.

PMID- 12058006
TI  - Assessing friend support of adolescents' diabetes care: the diabetes social
      support questionnaire-friends version.
AB  - OBJECTIVE: To develop and evaluate the Diabetes Social Support Questionnaire for
      Friends (DSSQ-Friends), a measure of friends' supportive behaviors for
      adolescents with diabetes. Gender and age differences in friends' support for
      diabetes were examined, as well as the relationship between friend support and
      adolescents' treatment adherence. METHODS: Seventy-four adolescents (11-18 years)
      completed the DSSQ-Friends in addition to other measures of social support and a
      measure of treatment adherence. The behaviors on the DSSQ-Friends were scored for
      supportiveness and frequency. A combined rating (frequency x support) was also
      calculated to adjust the frequency of friends' support for adolescents'
      perceptions of supportiveness. RESULTS: The DSSQ-Friends had acceptable internal
      consistency and good test-retest reliability; it correlated well with other
      measures of friend support. Age-related differences were minimal; however,
      compared to boys, girls reported more friend support for blood glucose testing
      and emotions. Friend support was not related to overall treatment adherence but
      was related to adherence for blood glucose testing. CONCLUSIONS: We discuss the
      utility of the DSSQ-Friends as a clinical and research tool for measuring
      diabetes-specific friend support and offer suggestions for future research on
      friends' support for adolescents' diabetes care.

PMID- 12058007
TI  - Peer and family support in children and adolescents with type 1 diabetes.
AB  - OBJECTIVE: To examine social support and peer and family involvement in relation
      to diabetes management within a developmental context. METHODS: Sixty-eight
      youths ages 8 to 17 diagnosed with type 1 diabetes participated. This study
      represents the phase 1 data from a multisystemic, home-based intervention. Data
      included parent and youth report of disease management and conflict, youth
      reported perceptions of support, peer participation in the intervention, and
      HbA1c. RESULTS: Adolescents perceived greater diabetes-related peer support than
      did school-age children. Perceived peer and family support were not correlated
      with metabolic control. Peer participation in the intervention was correlated
      with metabolic control. CONCLUSIONS: There is a developmental shift in
      perceptions of peer support. Increased perceptions of peer and family support
      overall may not result in improved metabolic control. Social support
      interventions should focus on the types of support that are most highly
      associated with positive health outcomes.

PMID- 12058008
TI  - "Come on, say something, dad!": communication and coping in fathers of diabetic
      adolescents.
AB  - OBJECTIVE: To investigate fathers' coping and communication behavior in families
      with a healthy or a diabetic adolescent. METHOD: Fathers of diabetic adolescents
      and healthy adolescents (N = 134) were investigated longitudinally with respect
      to their non-illness-specific coping behavior, their perceptions of family
      climate, and communicative behavior in solving a joint family task. Data were
      obtained through questionnaires and content analysis of recordings of verbal
      communication activity. RESULTS: Based on questionnaire data, few differences
      were found between diabetic and healthy adolescents' fathers' styles of coping
      with non-illness-specific family problems over time. However, several significant
      differences emerged, both with respect to the fathers' perceptions of family
      climate and to aspects of family communication, as observed by independent
      raters. The findings revealed the overall low communicative activity and
      initiative of diabetic adolescents' fathers, despite the diabetic adolescents'
      frequent efforts to involve their fathers in solving a joint task. CONCLUSIONS:
      Counseling and related support services for families of chronically ill
      adolescents should endeavor to reinstate or increase the father's involvement in
      the family, thereby encouraging him to exercise his distinctive parental
      functions.

PMID- 12058009
TI  - The intersection of adolescent development and intensive intervention: age
      related psychosocial correlates of treatment regimens in the diabetes control and
      complication trial.
AB  - OBJECTIVE: To provide evidence relevant to developmentally sensitive intervention
      and prevention of adolescents' psychosocial distress associated with treatment of
      type 1 diabetes. METHODS: We used self-reports on the Diabetes Quality of Life
      and SCL-90-R inventories administered at baseline, 1, and 3 years following
      adolescents' (n = 224) entry into the Diabetes Control and Complications Trial.
      RESULTS: Initiation of intensive treatment in early adolescence was associated
      with increasing school dissatisfaction; initiation in later adolescence resulted
      in marginal elevations in psychological distress. CONCLUSIONS: Age at entry
      moderates impact of intensive treatment on reported psychosocial distress.
      Intervention and prevention efforts sensitive to the interaction of developmental
      tasks with health treatment goals may optimize the well-being of adolescents with
      type 1 diabetes.

PMID- 12058010
TI  - A longitudinal study of pubertal timing, parent-child conflict, and cohesion in
      families of young adolescents with spina bifida.
AB  - OBJECTIVE: To study longitudinal associations between perceived pubertal timing
      and family conflict and cohesion during the transition to adolescence in 68
      families of children with spina bifida and 68 matched families with able-bodied
      children. Children were 8 or 9 years old at Time 1 and 10 or 11 years old at Time
      2. METHODS: Family conflict and cohesion were assessed with observational data
      and maternal, paternal, and child reports on questionnaires. Perceived pubertal
      timing was assessed with maternal report. RESULTS: Consistent with the literature
      on typically developing young adolescents, prospective longitudinal analyses
      revealed that early maturity was associated with higher levels of conflict and
      decreases in cohesion in families with able-bodied children. Contrary to these
      findings, perceived pubertal timing had less of an impact (or the opposite
      impact) in families of children with spina bifida. Findings were robust across
      respondents and methods of data collection. CONCLUSIONS: Findings based on
      multimethod and multisource data suggest that familial response to developmental
      change differs across context (spina bifida vs. able-bodied). Possible reasons
      for differential responses to the adolescent transition are reviewed. Services
      are likely to be enhanced if health professionals routinely discuss adolescent
      developmental issues with parents and youths during clinic visits.

PMID- 12058011
TI  - Parent factors and adolescent sickle cell disease: associations with patterns of
      health service use.
AB  - OBJECTIVE: To examine relationships among parent characteristics (parent
      adolescent relationship, parents' illness knowledge, and parents' perceptions of
      illness-related burden) and use of routine and urgent health services among
      adolescents with sickle cell disease (SCD). METHOD: Seventy adolescents, ages 12
      18, and their parents completed questionnaires assessing illness knowledge,
      perceptions of illness burden, parent-adolescent relationships, and adolescents'
      psychological functioning. Information about pain, routine services (i.e., care
      at home, clinic visits) and urgent service use (i.e., emergency department
      visits, hospitalizations) was obtained from parents and medical records. RESULTS:
      After we controlled for disease severity and life events, parents' perception of
      more illness-related stress was the strongest predictor of both types of service
      use. Greater parental knowledge about SCD also related to higher frequency of
      routine service use. Disease severity was strongly associated with frequency of
      urgent service use. CONCLUSIONS: Both parent characteristics and disease severity
      were associated with patterns of service use. Enhancing aspects of parental
      functioning may help families make adaptive decisions regarding health care
      services for SCD pain management.

PMID- 12058013
TI  - Protein kinase C betaII and TGFbetaRII in omega-3 fatty acid-mediated inhibition
      of colon carcinogenesis.
AB  - Increasing evidence demonstrates that protein kinase C betaII (PKCbetaII)
      promotes colon carcinogenesis. We previously reported that colonic PKCbetaII is
      induced during colon carcinogenesis in rodents and humans, and that elevated
      expression of PKCbetaII in the colon of transgenic mice enhances colon
      carcinogenesis. Here, we demonstrate that PKCbetaII represses transforming growth
      factor beta receptor type II (TGFbetaRII) expression and reduces sensitivity to
      TGF-beta-mediated growth inhibition in intestinal epithelial cells. Transgenic
      PKCbetaII mice exhibit hyperproliferation, enhanced colon carcinogenesis, and
      marked repression of TGFbetaRII expression. Chemopreventive dietary omega-3 fatty
      acids inhibit colonic PKCbetaII activity in vivo and block PKCbetaII-mediated
      hyperproliferation, enhanced carcinogenesis, and repression of TGFbetaRII
      expression in the colonic epithelium of transgenic PKCbetaII mice. These data
      indicate that dietary omega-3 fatty acids prevent colon cancer, at least in part,
      through inhibition of colonic PKCbetaII signaling and restoration of TGF-beta
      responsiveness.

PMID- 12058012
TI  - Np95 is regulated by E1A during mitotic reactivation of terminally differentiated
      cells and is essential for S phase entry.
AB  - Terminal differentiation exerts a remarkably tight control on cell proliferation.
      However, the oncogenic products of DNA tumor viruses, such as adenovirus E1A, can
      force postmitotic cells to proliferate, thus representing a powerful tool to
      study progression into S phase. In this study, we identified the gene encoding
      Np95, a murine nuclear phosphoprotein, as an early target of E1A-induced
      transcriptional events. In terminally differentiated (TD) cells, the activation
      of Np95 was specifically induced by E1A, but not by overexpression of E2F-1 or of
      the cyclin E (cycE)-cyclin-dependent kinase 2 (cdk2) complex. In addition, the
      concomitant expression of Np95 and of cycE-cdk2 was alone sufficient to induce S
      phase in TD cells. In NIH-3T3 cells, the expression of Np95 was tightly regulated
      during the cell cycle, and its functional ablation resulted in abrogation of DNA
      synthesis. Thus, expression of Np95 is essential for S phase entry. Previous
      evidence suggested that E1A, in addition to its well characterized effects on the
      pRb/E2F-1 pathway, activates a parallel and complementary pathway that is also
      required for the reentry in S phase of TD cells (Tiainen, M., D. Spitkousky, P.
      Jansen-Durr, A. Sacchi, and M. Crescenzi. 1996. Mol. Cell. Biol. 16:5302-5312).
      From our results, Np95 appears to possess all the characteristics to represent
      the first molecular determinant identified in this pathway.

PMID- 12058014
TI  - Rlp7p is associated with 60S preribosomes, restricted to the granular component
      of the nucleolus, and required for pre-rRNA processing.
AB  - Many analyses have examined subnucleolar structures in eukaryotic cells, but the
      relationship between morphological structures, pre-rRNA processing, and ribosomal
      particle assembly has remained unclear. Using a visual assay for export of the
      60S ribosomal subunit, we isolated a ts-lethal mutation, rix9-1, which causes
      nucleolar accumulation of an Rpl25p-eGFP reporter construct. The mutation results
      in a single amino acid substitution (F176S) in Rlp7p, an essential nucleolar
      protein related to ribosomal protein Rpl7p. The rix9-1 (rlp7-1) mutation blocks
      the late pre-RNA cleavage at site C2 in ITS2, which separates the precursors to
      the 5.8S and 25S rRNAs. Consistent with this, synthesis of the mature 5.8S and
      25S rRNAs was blocked in the rlp7-1 strain at nonpermissive temperature, whereas
      18S rRNA synthesis continued. Moreover, pre-rRNA containing ITS2 accumulates in
      the nucleolus of rix9-1 cells as revealed by in situ hybridization. Finally,
      tagged Rlp7p was shown to associate with a pre-60S particle, and fluorescence
      microscopy and immuno-EM localized Rlp7p to a subregion of the nucleolus, which
      could be the granular component (GC). All together, these data suggest that pre
      rRNA cleavage at site C2 specifically requires Rlp7p and occurs within pre-60S
      particles located in the GC region of the nucleolus.

PMID- 12058015
TI  - The mechanism of inhibition of Ran-dependent nuclear transport by cellular ATP
      depletion.
AB  - Rran-dependent nuclear transport requires a nuclear pool of RanGTP both for the
      assembly of export complexes and the disassembly of import complexes.
      Accordingly, in order for these processes to proceed, Ran-dependent nuclear
      import and export assays in vitro require the addition of GTP to produce RanGTP.
      Notably, no ATP requirement can be detected for these transport processes in
      vitro. But in vivo, when cells are depleted of ATP by the addition of sodium
      azide and 2-deoxyglucose to block ATP production by oxidative phosphorylation and
      glycolysis, respectively, Ran-dependent nuclear import and export are rapidly
      inhibited. This raised the question of whether there is an ATP requirement for
      these nuclear transport pathways in an intact cell that has remained undetected
      in vitro. Here we report that the free (but not total) GTP concentration rapidly
      drops to an undetectable level upon ATP depletion as does the availability of
      RanGTP. Our conclusion is that the inhibition of Ran-dependent nuclear transport
      observed upon ATP depletion in vivo results from a shortage of RanGTP rather than
      the inhibition of some ATP-dependent process.

PMID- 12058016
TI  - Huntington toxicity in yeast model depends on polyglutamine aggregation mediated
      by a prion-like protein Rnq1.
AB  - The cause of Huntington's disease is expansion of polyglutamine (polyQ) domain in
      huntingtin, which makes this protein both neurotoxic and aggregation prone. Here
      we developed the first yeast model, which establishes a direct link between
      aggregation of expanded polyQ domain and its cytotoxicity. Our data indicated
      that deficiencies in molecular chaperones Sis1 and Hsp104 inhibited seeding of
      polyQ aggregates, whereas ssa1, ssa2, and ydj1-151 mutations inhibited expansion
      of aggregates. The latter three mutants strongly suppressed the polyQ toxicity.
      Spontaneous mutants with suppressed aggregation appeared with high frequency, and
      in all of them the toxicity was relieved. Aggregation defects in these mutants
      and in sis1-85 were not complemented in the cross to the hsp104 mutant,
      demonstrating an unusual type of inheritance. Since Hsp104 is required for prion
      maintenance in yeast, this suggested a role for prions in polyQ aggregation and
      toxicity. We screened a set of deletions of nonessential genes coding for known
      prions and related proteins and found that deletion of the RNQ1 gene specifically
      suppressed aggregation and toxicity of polyQ. Curing of the prion form of Rnq1
      from wild-type cells dramatically suppressed both aggregation and toxicity of
      polyQ. We concluded that aggregation of polyQ is critical for its toxicity and
      that Rnq1 in its prion conformation plays an essential role in polyQ aggregation
      leading to the toxicity.

PMID- 12058017
TI  - Cod1p/Spf1p is a P-type ATPase involved in ER function and Ca2+ homeostasis.
AB  - The internal environment of the ER is regulated to accommodate essential cellular
      processes, yet our understanding of this regulation remains incomplete.
      Cod1p/Spf1p belongs to the widely conserved, uncharacterized type V branch of P
      type ATPases, a large family of ion pumps. Our previous work suggested Cod1p may
      function in the ER. Consistent with this hypothesis, we localized Cod1p to the ER
      membrane. The cod1Delta mutant disrupted cellular calcium homeostasis, causing
      increased transcription of calcium-regulated genes and a synergistic increase in
      cellular calcium when paired with disruption of the Golgi apparatus-localized
      Ca2+ pump Pmr1p. Deletion of COD1 also impaired ER function, causing constitutive
      activation of the unfolded protein response, hypersensitivity to the
      glycosylation inhibitor tunicamycin, and synthetic lethality with deletion of the
      unfolded protein response regulator HAC1. Expression of the Drosophila
      melanogaster homologue of Cod1p complemented the cod1Delta mutant. Finally, we
      demonstrated the ATPase activity of the purified protein. This study provides the
      first biochemical characterization of a type V P-type ATPase, implicates Cod1p in
      ER function and ion homeostasis, and indicates that these functions are conserved
      among Cod1p's metazoan homologues.

PMID- 12058019
TI  - The adenomatous polyposis coli protein unambiguously localizes to microtubule
      plus ends and is involved in establishing parallel arrays of microtubule bundles
      in highly polarized epithelial cells.
AB  - Loss of full-length adenomatous polyposis coli (APC) protein correlates with the
      development of colon cancers in familial and sporadic cases. In addition to its
      role in regulating beta-catenin levels in the Wnt signaling pathway, the APC
      protein is implicated in regulating cytoskeletal organization. APC stabilizes
      microtubules in vivo and in vitro, and this may play a role in cell migration
      (Nathke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J.
      Cell Biol. 134:165-179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J.
      Cell Biol. 148:505-517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Nathke.
      2001. Curr. Biol. 11:44-49) and in the attachment of microtubules to kinetochores
      during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C.
      Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001.
      Nat. Cell Biol. 3:433-438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K.
      Sorger, and I.S. Nathke. 2001. Nat. Cell Biol. 3:429-432). The localization of
      endogenous APC protein is complex: actin- and microtubule-dependent pools of APC
      have been identified in cultured cells (Nathke et al., 1996; Mimori-Kiyosue et
      al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491
      502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929-5939).
      However, the localization of APC in tissues has not been identified at high
      resolution. Here, we show that in fully polarized epithelial cells from the inner
      ear, endogenous APC protein associates with the plus ends of microtubules located
      at the basal plasma membrane. Consistent with a role for APC in supporting the
      cytoskeletal organization of epithelial cells in vivo, the number of microtubules
      is significantly reduced in apico-basal arrays of microtubule bundles isolated
      from mice heterozygous for APC.

PMID- 12058018
TI  - The endoplasmic reticulum cation P-type ATPase Cta4p is required for control of
      cell shape and microtubule dynamics.
AB  - Here we describe the phenotypic characterization of the cta4+ gene, encoding a
      novel member of the P4 family of P-type ATPases of fission yeast. The cta4Delta
      mutant is temperature sensitive and cold sensitive lethal and displays several
      morphological defects in cell polarity and cytokinesis. Microtubules are
      generally destabilized in cells lacking Cta4p. The microtubule length is
      decreased, and the number of microtubules per cell is increased. This is
      concomitant with an increase in the number of microtubule catastrophe events in
      the midzone of the cell. These defects are likely due to a general imbalance in
      cation homeostasis. Immunofluorescence microscopy and membrane fractionation
      experiments revealed that green fluorescent protein-tagged Cta4 localizes to the
      ER. Fluorescence resonance energy transfer experiments in living cells using the
      yellow cameleon indicator for Ca2+ indicated that Cta4p regulates the cellular
      Ca2+ concentration. Thus, our results reveal a link between cation homeostasis
      and the control of cell shape, microtubule dynamics, and cytokinesis, and appoint
      Ca2+ as a key ion in controlling these processes.

PMID- 12058020
TI  - Bone morphogenetic protein receptor signaling is necessary for normal murine
      postnatal bone formation.
AB  - Functions of bone morphogenetic proteins (BMPs) are initiated by signaling
      through specific type I and type II serine/threonine kinase receptors. In
      previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB)
      plays an essential and specific role in osteoblast commitment and
      differentiation. To determine the role of BMP receptor signaling in bone
      formation in vivo, we generated transgenic mice, which express a truncated
      dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen
      promoter. The mice are viable and fertile. Tissue-specific expression of the
      truncated BMPR-IB was demonstrated. Characterization of the phenotype of these
      transgenic mice showed impairment of postnatal bone formation in 1-mo-old
      homozygous transgenic mice. Bone mineral density, bone volume, and bone formation
      rates were severely reduced, but osteoblast and osteoclast numbers were not
      significantly changed in the transgenic mice. To determine whether osteoblast
      differentiation is impaired, we used primary osteoblasts isolated from the
      transgenic mice and showed that BMP signaling is blocked and BMP2-induced
      mineralized bone matrix formation was inhibited. These studies show the effects
      of alterations in BMP receptor function targeted to the osteoblast lineage and
      demonstrate a necessary role of BMP receptor signaling in postnatal bone growth
      and bone formation in vivo.

PMID- 12058021
TI  - Phospholipids undergo hop diffusion in compartmentalized cell membrane.
AB  - The diffusion rate of lipids in the cell membrane is reduced by a factor of 5-100
      from that in artificial bilayers. This slowing mechanism has puzzled cell
      biologists for the last 25 yr. Here we address this issue by studying the
      movement of unsaturated phospholipids in rat kidney fibroblasts at the single
      molecule level at the temporal resolution of 25 micros. The cell membrane was
      found to be compartmentalized: phospholipids are confined within 230-nm-diameter
      (phi) compartments for 11 ms on average before hopping to adjacent compartments.
      These 230-nm compartments exist within greater 750-nm-phi compartments where
      these phospholipids are confined for 0.33 s on average. The diffusion rate within
      230-nm compartments is 5.4 microm2/s, which is nearly as fast as that in large
      unilamellar vesicles, indicating that the diffusion in the cell membrane is
      reduced not because diffusion per se is slow, but because the cell membrane is
      compartmentalized with regard to lateral diffusion of phospholipids. Such
      compartmentalization depends on the actin-based membrane skeleton, but not on the
      extracellular matrix, extracellular domains of membrane proteins, or cholesterol
      enriched rafts. We propose that various transmembrane proteins anchored to the
      actin-based membrane skeleton meshwork act as rows of pickets that temporarily
      confine phospholipids.

PMID- 12058023
TI  - Localization of the Rsr1/Bud1 GTPase involved in selection of a proper growth
      site in yeast.
AB  - Yeast cells organize their actin cytoskeleton in a highly polarized manner during
      vegetative growth. The Ras-like GTPase Rsr1/Bud1 and its regulators are required
      for selection of a specific site for growth. Here we showed that Rsr1/Bud1 was
      broadly distributed on the plasma membrane and highly concentrated at the
      incipient bud site and polarized growth sites. We also showed that localization
      of Cdc24, a guanine nucleotide exchange factor for the Cdc42 GTPase, to the
      proper bud site was dependent on Rsr1/Bud1. Surprisingly, Rsr1/Bud1 also
      localized to intracellular membranes. A mutation in the lysine repeat in the
      hypervariable region of Rsr1/Bud1 specifically abolished its plasma membrane
      localization, whereas a mutation at the CAAX motif eliminated both plasma
      membrane and internal membrane association of Rsr1/Bud1. Thus the lysine repeat
      and the CAAX motif of Rsr1/Bud1 are important for its localization to the plasma
      membrane and to the polarized growth sites. This localization of Rsr1/Bud1 is
      essential for its function in proper bud site selection because both mutations
      resulted in random bud site selection.

PMID- 12058022
TI  - Slow local movements of collagen fibers by fibroblasts drive the rapid global
      self-organization of collagen gels.
AB  - Aclassic model for tissue morphogenesis is the formation of ligament-like straps
      between explants of fibroblasts placed in collagen gels. The patterns arise from
      mechanical forces exerted by cells on their substrates (Harris et al., 1981).
      However, where do such straps come from, and how are slow local movements of
      cells transduced into dramatic long-distance redistributions of collagen? We
      embedded primary mouse skin and human periodontal ligament fibroblasts in
      collagen gels and measured the time course of patterning by using a novel
      computer algorithm to calculate anisotropy, and by tracking glass beads dispersed
      in the gel. As fibroblasts began to spread into their immediate environments, a
      coordinated rearrangement of collagen commenced throughout the gel, producing a
      strap on a time scale of minutes. Killing of cells afterwards resulted in a
      partial relaxation of the matrix strain. Surprisingly, relatively small movements
      of collagen molecules on the tensile axis between two pulling explants induced a
      much larger concomitant compression of the gel perpendicular to the axis,
      organizing and aligning fibers into a strap. We propose that this amplification
      is due to the geometry of the collagen matrix, and that analogous amplified
      movements may drive morphological changes in other biological meshes, both
      outside and inside the cell.

PMID- 12058024
TI  - Growth inhibitory factor prevents neurite extension and the death of cortical
      neurons caused by high oxygen exposure through hydroxyl radical scavenging.
AB  - Growth inhibitory factor (GIF), a brain-specific member of the metallothionein
      family (MT-III), has been characterized as a inhibitory substance for
      neurotrophic factors in Alzheimer's disease brains. However, the function of GIF,
      other than the inhibition of neurotrophic factors, remains unknown. We
      demonstrate here that exogenous GIF prevents neurite extension of cortical
      neurons in the early period of differentiation and the death of differentiated
      neurons caused by high oxygen exposure. Down-regulation of GIF in cortical
      neurons with antisense S-oligonucleotides promoted neuronal death under high
      oxygen conditions. ESR spin-trapping studies demonstrated that GIF at 2-6 microm
      scavenged hydroxyl radicals generated by a Fenton-type reaction or the photolysis
      of hydrogen peroxide much more effectively than the same concentration of
      metallothionein I+II. GIF did not scavenge either superoxide produced by the
      xanthine/xanthine oxidase reaction or NO generated from 1-hydroxy-2-oxo-3-(N
      methyl-3-aminopropyl)-3-methyl-1-triazene. Moreover, GIF at 40-80 microm
      inhibited tyrosine nitration by peroxynitrite as efficiently as metallothionein
      I+II at the same concentration. These results indicate that GIF prevents neurite
      extension of neurons in the early period of differentiation and supports the
      survival of differentiated neurons by scavenging hydroxyl radicals.

PMID- 12058025
TI  - A new splice variant of glial fibrillary acidic protein, GFAP epsilon, interacts
      with the presenilin proteins.
AB  - We describe a new human isoform, GFAP epsilon, of the intermediary filament
      protein GFAP (glial fibrillary acidic protein). GFAP epsilon mRNA is the result
      of alternative splicing and a new polyadenylation signal, and thus GFAP epsilon
      has a new C-terminal protein sequence. This provides GFAP epsilon with the
      capacity for specific binding of presenilin proteins in yeast and in vitro. Our
      observations suggest a direct link between the presenilins and the cytoskeleton
      where GFAP epsilon is incorporated. Mutations in GFAP and presenilins are
      associated with Alexander disease and Alzheimer's disease, respectively.
      Accordingly, GFAP epsilon should be taken into consideration when studying
      neurodegenerative diseases.

PMID- 12058026
TI  - A novel specific role for I kappa B kinase complex-associated protein in
      cytosolic stress signaling.
AB  - We demonstrate here a novel role for the I kappa B kinase complex-associated
      protein (IKAP) in the regulation of activation of the mammalian stress response
      via the c-Jun N-terminal kinase (JNK)-signaling pathway. We cloned IKAP as a JNK
      associating protein using the Ras recruitment yeast two-hybrid system. IKAP
      efficiently and specifically enhanced JNK activation induced by ectopic
      expression of MEKK1 and ASK1, upstream activators of JNK. Importantly, IKAP also
      enhanced JNK activation induced by ultraviolet light irradiation as well as
      treatments with tumor necrosis factor or epidermal growth factor. The JNK
      association site in IKAP was mapped to the C-terminal part of IKAP.
      Interestingly, this region is deleted from IKAP expressed in the autonomous
      nervous system of the patients affected by familial dysautonomia. Ectopic
      expression of this C-terminal fragment of IKAP was sufficient to support JNK
      activation. Taken together, our data demonstrate a novel role for IKAP in the
      regulation of the JNK-mediated stress signaling. Additionally, our results point
      to a role of JNK signaling in familial dysautonomia and, thus, further support
      the involvement of JNK signaling in the development, survival, and degeneration
      of the sensory and autonomic nervous system.

PMID- 12058027
TI  - Mechanism of activation of protein kinase D2(PKD2) by the CCK(B)/gastrin
      receptor.
AB  - Recently, we cloned a novel serine/threonine kinase termed protein kinase D2
      (PKD2). PKD2 can be activated by phorbol esters both in vivo and in vitro but
      also by gastrin via the cholecystokinin/CCK(B) receptor in human gastric cancer
      cells stably transfected with the CCK(B)/gastrin receptor (AGS-B cells). Here we
      identify the mechanisms of gastrin-induced PKD2 activation in AGS-B cells. PKD2
      phosphorylation in response to gastrin was rapid, reaching a maximum after 10 min
      of incubation. Our data demonstrate that gastrin-stimulated PKD2 activation
      involves a heterotrimeric G alpha(q) protein as well as the activation of
      phospholipase C. Furthermore, we show that PKD2 can be activated by classical and
      novel members of the protein kinase C (PKC) family such as PKC alpha, PKC
      epsilon, and PKC eta. These PKCs are activated by gastrin in AGS-B cells. Thus,
      PKD2 is likely to be a novel downstream target of specific PKCs upon the
      stimulation of AGS-B cells with gastrin. Our data suggest a two-step mechanism of
      activation of PKD2 via endogenously produced diacylglycerol and the activation of
      PKCs.

PMID- 12058028
TI  - The stress-activated protein kinases p38 alpha and JNK1 stabilize p21(Cip1) by
      phosphorylation.
AB  - Stress signals activate the SAPK/JNK and p38 MAPK classes of protein kinases,
      which mediate cellular responses, including steps in apoptosis and the maturation
      of some cell types. We now show that stress signals initiated by transforming
      growth factor-beta 1 (TGF-beta 1) induce G(1) arrest through protein
      stabilization of the CDK inhibitor p21(Cip1). TGF-beta 1 was previously shown to
      increase p21 protein levels, which in turn mediated G(1) arrest through
      inactivation of the CDK2-cyclin E complex in HD3 cells (Yan, Z., Kim, G.-Y.,
      Deng, X., and Friedman, E. (2002) J. Biol. Chem. 277, 9870-9879). We now
      demonstrate that the increase in p21 abundance is caused by a post
      transcriptional, SMAD-independent mechanism. TGF-beta1 activated p38 alpha and
      JNK1, which initiated the phosphorylation of p21. TGF-beta1 treatment increased
      the half-life of p21 by 3-4-fold. The increase in p21 stability was detected
      following activation of p38 alpha and JNK1, and treatment of cells with the p38
      inhibitor SB203580 prevented this increase in p21 stability. p38 alpha and JNK1
      phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at
      Ser(130) in vitro. Peptide mapping demonstrated that both TGF-beta 1 and p38
      alpha induced phosphorylation of p21 at Ser(130) in vivo, and mutation of
      Ser(130) to alanine rendered p21 less stable than wild-type p21. TGF-beta 1
      increased the stability of wild-type p21, but not the p21-S130A mutant. These
      findings demonstrate that SAPKs can mediate cell cycle arrest through post
      translational modification of p21.

PMID- 12058029
TI  - Microaerophilic conditions permit to mimic in vitro events occurring during in
      vivo Helicobacter pylori infection and to identify Rho/Ras-associated proteins in
      cellular signaling.
AB  - Molecular dissection of the mechanisms underlying Helicobacter pylori infection
      suffers from the lack of in vitro systems mimicking in vivo observations. A
      system was developed whereby human epithelial cells (Caco-2) grown as polarized
      monolayers and bacteria can communicate with each other under culture conditions
      optimal for each partner. Caco-2 cells grown on filter supports were inserted in
      a vertical position into diffusion chambers equilibrated with air and 5% CO(2) at
      their basolateral surface (aerophilic conditions) and 5% CO(2), 5% O(2), 90% N(2)
      (microaerophilic conditions) in the apical compartment. Remarkably, the
      epithelial polarized layer was stable under these asymmetric culture conditions
      for at least 24 h, and the presence of Caco-2 cells was necessary to maintain H.
      pylori growth. In contrast to previous studies conducted with non-polarized Caco
      2 cells and other cell lines kept under aerophilic conditions, we found H. pylori
      dependent stimulation of cytokine secretion (MCP-1 (monocyte chemoattractant
      protein-1), GRO-alpha (growth-regulated oncogene-alpha), RANTES (regulated on
      activation normal T cell expressed and secreted)). This correlated with nuclear
      translocation of NF-kappaB p50 and p65 subunits. Tyrosine phosphorylation of nine
      cellular proteins was induced or enhanced; we identified p120(RasGAP),
      p190(RhoGAP), p62dok (downstream of tyrosine kinases), and cortactin as H. pylori
      inducible targets. Moreover, reduction of H. pylori urease expression was
      observed in adherent bacteria as compared with bacteria in suspension. In
      addition to mimicking several observations seen in the inflamed gastric mucosa,
      the novel in vitro system was allowed to underscore complex cellular events not
      seen in classical in vitro analyses of microaerophilic bacteria-epithelial cell
      cross-talk.

PMID- 12058030
TI  - Oligomeric and fibrillar species of amyloid-beta peptides differentially affect
      neuronal viability.
AB  - Genetic evidence predicts a causative role for amyloid-beta (A beta) in
      Alzheimer's disease. Recent debate has focused on whether fibrils (amyloid) or
      soluble oligomers of A beta are the active species that contribute to
      neurodegeneration and dementia. We developed two aggregation protocols for the
      consistent production of stable oligomeric or fibrillar preparations of A beta-(1
      42). Here we report that oligomers inhibit neuronal viability 10-fold more than
      fibrils and approximately 40-fold more than unaggregated peptide, with oligomeric
      A beta-(1-42)-induced inhibition significant at 10 nm. Under A beta-(1-42)
      oligomer- and fibril-forming conditions, A beta-(1-40) remains predominantly as
      unassembled monomer and had significantly less effect on neuronal viability than
      preparations of A beta-(1-42). We applied the aggregation protocols developed for
      wild type A beta-(1-42) to A beta-(1-42) with the Dutch (E22Q) or Arctic (E22G)
      mutations. Oligomeric preparations of the mutations exhibited extensive
      protofibril and fibril formation, respectively, but were not consistently
      different from wild type A beta-(1-42) in terms of inhibition of neuronal
      viability. However, fibrillar preparations of the mutants appeared larger and
      induced significantly more inhibition of neuronal viability than wild type A beta
      (1-42) fibril preparations. These data demonstrate that protocols developed to
      produce oligomeric and fibrillar A beta-(1-42) are useful in distinguishing the
      structural and functional differences between A beta-(1-42) and A beta-(1-40) and
      genetic mutations of A beta-(1-42).

PMID- 12058031
TI  - Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is
      activated by the endoprotease furin.
AB  - N-Acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, also known as
      "uncovering" enzyme (UCE), is localized in the trans-Golgi network, where it
      removes a covering N-acetylglucosamine from the mannose 6-phosphate recognition
      marker on lysosomal acid hydrolases. Here we show that UCE is synthesized as an
      inactive proenzyme that is activated by the endoprotease furin, which cleaves an
      RARLPR/D sequence to release a 24-amino acid propiece. As furin is localized in
      the trans-Golgi network, newly synthesized UCE is inactive until it reaches this
      terminal Golgi compartment. LoVo cells (derived from a human colon
      adenocarcinoma) lack furin activity and have extremely low UCE activity. Addition
      of furin to LoVo cell extracts restores UCE activity to normal levels,
      demonstrating that the UCE proenzyme is stable in this cell type. LoVo cells
      secrete acid hydrolases with phosphomannose diesters as a consequence of the
      deficient UCE activity. This demonstrates for the first time that UCE is the only
      enzyme in these cells capable of efficiently uncovering phosphomannose diesters.
      UCE also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N
      acetylglucosaminyltransferases. The fact that UCE is not activated until it
      reaches the trans-Golgi network may ensure that the pool of UDP-GlcNAc in the
      Golgi stack is not depleted, thereby maintaining proper oligosaccharide assembly.

PMID- 12058032
TI  - Sustained production of H(2)O(2) activates pro-matrix metalloproteinase-2 through
      receptor tyrosine kinases/phosphatidylinositol 3-kinase/NF-kappa B pathway.
AB  - A rate-limiting step of tumor cell metastasis is matrix degradation by active
      matrix metalloproteinases (MMPs). It is known that reactive oxygen species are
      involved in tumor metastasis. Sustained production of H(2)O(2) by phenazine
      methosulfate (PMS) induced activation of pro-MMP-2 through the induction of
      membrane type 1-MMP (MT1-MMP) expression in HT1080 cells. MMP-2, MMP-9, and
      tissue inhibitor of metalloproteinase-1 and -2 levels were changed negligibly by
      PMS. A one time treatment with H(2)O(2) did not induce activation of MMPs. It was
      also demonstrated that superoxide anions and hydroxyl radicals were not related
      to PMS action. PMS-induced pro-MMP-2 activation was regulated by the receptor
      tyrosine kinases, especially the receptors of platelet-derived growth factor and
      vascular endothelial growth factor, and downstream on the phosphatidylinositol 3
      kinase/NF-kappa B pathway but not Ras, cAMP-dependent protein kinase, protein
      kinase C, and mitogen-activated protein kinases. PMS did not induce pro-MMP-2
      activation in T98G and NIH3T3 cells. This may be related to a low level of MT1
      MMP, indicating a threshold level of MT1-MMP is important for pro-MMP-2
      activation. Furthermore, PMS increased cell motility and invasion but decreased
      cell-cell interaction. Cell-matrix interaction was not affected by PMS.

PMID- 12058033
TI  - Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p
      signaling pathway in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the Ca(2+)/calmodulin-dependent protein phosphatase,
      calcineurin, is activated by specific environmental conditions, including
      exposure to Ca(2+) and Na(+), and induces gene expression by regulating the
      Crz1p/Tcn1p transcription factor. We used DNA microarrays to perform a
      comprehensive analysis of calcineurin/Crz1p-dependent gene expression following
      addition of Ca(2+) (200 mm) or Na(+) (0.8 m) to yeast. 163 genes exhibited
      increased expression that was reduced 50% or more by calcineurin inhibition.
      These calcineurin-dependent genes function in signaling pathways, ion/small
      molecule transport, cell wall maintenance, and vesicular transport, and include
      many open reading frames of previously unknown function. Three distinct gene
      classes were defined as follows: 28 genes displayed calcineurin-dependent
      induction in response to Ca(2+) and Na(+), 125 showed calcineurin-dependent
      expression following Ca(2+) but not Na(+) addition, and 10 were regulated by
      calcineurin in response to Na(+) but not Ca(2+). Analysis of crz1Delta cells
      established Crz1p as the major effector of calcineurin-regulated gene expression
      in yeast. We identified the Crz1p-binding site as 5'-GNGGC(G/T)CA-3' by in vitro
      site selection. A similar sequence, 5'-GAGGCTG-3', was identified as a common
      sequence motif in the upstream regions of calcineurin/ Crz1p-dependent genes.
      This finding is consistent with direct regulation of these genes by Crz1p.

PMID- 12058034
TI  - BAG4/SODD protein contains a short BAG domain.
AB  - BAG (Bcl-2-associated athanogene) proteins are molecular chaperone regulators
      that affect diverse cellular pathways. All members share a conserved motif,
      called the BAG domain (BD), which binds to Hsp70/Hsc70 family proteins and
      modulates their activity. We have determined the solution structure of BD from
      BAG4/SODD (silencer of death domains) by multidimensional nuclear magnetic
      resonance methods and compared it to the corresponding domain in BAG1
      (Briknarova, K., Takayama, S., Brive, L., Havert, M. L., Knee, D. A., Velasco,
      J., Homma, S., Cabezas, E., Stuart, J., Hoyt, D. W., Satterthwait, A. C., Llinas,
      M., Reed, J. C., and Ely, K. R. (2001) Nat. Struct. Biol. 8, 349-352). The
      difference between BDs from these two BAG proteins is striking, and the
      structural comparison defines two subfamilies of mammalian BD-containing
      proteins. One subfamily includes the closely related BAG3, BAG4, and BAG5
      proteins, and the other is represented by BAG1, which contains a structurally and
      evolutionarily distinct BD. BDs from both BAG1 and BAG4 are three-helix bundles;
      however, in BAG4, each helix in this bundle is three to four turns shorter than
      its counterpart in BAG1, which reduces the length of the domain by one-third.
      BAG4 BD thus represents a prototype of the minimal functional fragment that is
      capable of binding to Hsc70 and modulating its chaperone activity.

PMID- 12058035
TI  - Involvement of protein kinase C activation and cell survival/ cell cycle genes in
      green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action.
AB  - Studies from our laboratory have demonstrated that the major green tea
      polyphenol, (-)-epigallocatechin 3-gallate (EGCG), exerts potent neuroprotective
      actions in the mice model of Parkinson's disease. These studies were extended to
      neuronal cell culture employing the parkinsonism-inducing neurotoxin, 6
      hydroxydopamine (6-OHDA). Pretreatment with EGCG (0.1-10 microm) attenuated human
      neuroblastoma (NB) SH-SY5Y cell death, induced by a 24-h exposure to 6-OHDA (50
      microm). Potential cell signaling candidates involved in this neuroprotective
      effect were further examined. EGCG restored the reduced protein kinase C (PKC)
      and extracellular signal-regulated kinases (ERK1/2) activities caused by 6-OHDA
      toxicity. However, the neuroprotective effect of EGCG on cell survival was
      abolished by pretreatment with PKC inhibitor GF 109203X (1 microm). Because EGCG
      increased phosphorylated PKC, we suggest that PKC isoenzymes are involved in the
      neuroprotective action of EGCG against 6-OHDA. In addition, gene expression
      analysis revealed that EGCG prevented both the 6-OHDA-induced expression of
      several mRNAs, such as Bax, Bad, and Mdm2, and the decrease in Bcl-2, Bcl-w, and
      Bcl-x(L). These results suggest that the neuroprotective mechanism of EGCG
      against oxidative stress-induced cell death includes stimulation of PKC and
      modulation of cell survival/cell cycle genes.

PMID- 12058036
TI  - Selective, reversible caspase-3 inhibitor is neuroprotective and reveals distinct
      pathways of cell death after neonatal hypoxic-ischemic brain injury.
AB  - Hypoxia-ischemia (H-I) in the developing brain results in brain injury with
      prominent features of both apoptosis and necrosis. A peptide-based pan-caspase
      inhibitor is neuroprotective against neonatal H-I brain injury, suggesting a
      central role of caspases in brain injury. Because previously studied peptide
      based caspase inhibitors are not potent and are only partially selective, the
      exact contribution of specific caspases and other proteases to injury after H-I
      is not clear. In this study, we explored the neuroprotective effects of a small,
      reversible caspase-3 inhibitor M826. M826 selectively and potently inhibited both
      caspase-3 enzymatic activity and apoptosis in cultured cells in vitro. In a rat
      model of neonatal H-I, M826 blocked caspase-3 activation and cleavage of its
      substrates, which begins 6 h and peaks 24 h after H-I. Although M826
      significantly reduced DNA fragmentation and brain tissue loss, it did not prevent
      calpain activation in the cortex. This activation, which is associated with
      excitotoxic/necrotic cell injury, occurred within 30 min to 2 h after H-I even in
      the presence of M826. Similar to calpain activation, we found evidence of caspase
      2 processing within 30 min to 2 h after H-I that was not affected by M826.
      Caspase-2 processing appeared to be secondary to calpain-mediated cleavage and
      was not associated with caspase-2 activation. These data suggest that caspase-3
      specifically contributes to delayed cell death and brain injury after neonatal H
      I and that calpain activation is associated with and likely a marker for the
      early component of excitotoxic/necrotic brain injury previously demonstrated in
      this model.

PMID- 12058037
TI  - Synthetic miniprion PrP106.
AB  - Elucidation of structure and biological properties of the prion protein scrapie
      (PrP(Sc)) is fundamental to an understanding of the mechanism of conformational
      transition of cellular (PrP(C)) into disease-specific isoforms and the
      pathogenesis of prion diseases. Unfortunately, the insolubility and heterogeneity
      of PrP(Sc) have limited these studies. The observation that a construct of 106
      amino acids (termed PrP106 or miniprion), derived from mouse PrP and containing
      two deletions (Delta 23-88, Delta 141-176), becomes protease-resistant when
      expressed in scrapie-infected neuroblastoma cells and sustains prion replication
      when expressed in PrP(0/0) mice prompted us to generate a corresponding synthetic
      peptide (sPrP106) to be used for biochemical and cell culture studies. sPrP106
      was obtained successfully with a straightforward procedure, which combines
      classical stepwise solid phase synthesis with a purification strategy based on
      transient labeling with a lipophilic chromatographic probe. sPrP106 readily
      adopted a beta-sheet structure, aggregated into branched filamentous structures
      without ultrastructural and tinctorial properties of amyloid, exhibited a
      proteinase K-resistant domain spanning residues 134-217, was highly toxic to
      primary neuronal cultures, and induced a remarkable increase in membrane
      microviscosity. These features are central properties of PrP(Sc) and make sPrP106
      an excellent tool for investigating the molecular basis of the conformational
      conversion of PrP(C) into PrP(Sc) and prion disease pathogenesis.

PMID- 12058038
TI  - Biosynthetic oligosaccharide libraries for identification of protein-binding
      heparan sulfate motifs. Exploring the structural diversity by screening for
      fibroblast growth factor (FGF)1 and FGF2 binding.
AB  - Heparan sulfate is crucial for vital reactions in the body because of its ability
      to bind various proteins. The identification of protein-binding heparan sulfate
      sequences is essential to our understanding of heparan sulfate biology and raises
      the possibility to develop drugs against diseases such as cancer and inflammatory
      conditions. We present proof-of-principle that in vitro generated heparan sulfate
      oligosaccharide libraries can be used to explore interactions between heparan
      sulfate and proteins, and that the libraries expand the available heparan sulfate
      sequence space. Oligosaccharide libraries mimicking highly 6-O-sulfated domains
      of heparan sulfate were constructed by enzymatic O-sulfation of O-desulfated, end
      group (3)H-labeled heparin octasaccharides. Acceptor oligosaccharides that were 6
      O-desulfated but only partially 2-O-desulfated yielded oligosaccharide arrays
      with increased ratio of iduronyl 2-O-sulfate/glucosaminyl 6-O-sulfate. The
      products were probed by affinity chromatography on immobilized growth factors,
      fibroblast growth factor-1 (FGF1) and FGF2, followed by sequence analysis of
      trapped oligosaccharides. An N-sulfated octasaccharide, devoid of 2-O-sulfate but
      with three 6-O-sulfate groups, was unexpectedly found to bind FGF1 as well as
      FGF2 at physiological ionic strength. However, a single 2-O-sulfate group in the
      absence of 6-O-sulfation gave higher affinity for FGF2. FGF1 binding was also
      augmented by 2-O-sulfation, preferentially in combination with an adjacent
      upstream 6-O-sulfate group. These results demonstrate the potential of the
      enzymatically generated oligosaccharide libraries.

PMID- 12058039
TI  - The role of the native lipids and lattice structure in bacteriorhodopsin protein
      conformation and stability as studied by temperature-dependent Fourier transform
      infrared spectroscopy.
AB  - We report the effect of partial delipidation and monomerization on the protein
      conformational changes of bacteriorhodopsin (bR) as a function of temperature.
      Removal of up to 75% of the lipids is known to have the lattice structure of the
      purple membrane, albeit as a smaller unit cell, whereas treatment by Triton
      monomerizes bR into micelles. The effects of these modifications on the protein
      secondary structure is analyzed by monitoring the protein amide I and amide II
      bands in the Fourier transform-infrared (FT-IR) spectra. It is found that removal
      of the first 75% of the lipids has only a slight effect on the secondary
      structure at physiological temperature, whereas monomerizing bR into micelles
      alters the secondary structure considerably. Upon heating, the bR monomer is
      found to have a very low thermal stability compared with the native bR with its
      melting point reduced from 97 to 65 degrees C, and the pre-melting transition in
      which the protein changes conformation in native bR at 80 degrees C could not be
      observed. Also, the N[bond]H to N[bond]D exchange of the amide II band is
      effectively complete at room temperature, suggesting that there are no
      hydrophobic regions that are protected from the aqueous medium, possibly
      explaining the low thermal stability of the monomer. On the other hand, 75%
      delipidated bR has its melting temperature close to that of the native bR and
      does have a pre-melting transition, although the pre-melting transition occurs at
      significantly higher temperature than that of the native bR (91 degrees C
      compared with 80 degrees C) and is still reversible. Furthermore, we have also
      observed that the reversibility of this pre-melting transition of both native and
      partially delipidated bR is time-dependent and becomes irreversible upon holding
      at 91 degrees C between 10 and 30 min. These results are discussed in terms of
      the lipid and lattice contribution to the protein thermal stability of native bR.

PMID- 12058040
TI  - Lack of pseudouridine 38/39 in the anticodon arm of yeast cytoplasmic tRNA
      decreases in vivo recoding efficiency.
AB  - Many different modified nucleotides are found in naturally occurring tRNA,
      especially in the anticodon region. Their importance for the efficiency of the
      translational process begins to be well documented. Here we have analyzed the in
      vivo effect of deleting genes coding for yeast tRNA-modifying enzymes, namely
      Pus1p, Pus3p, Pus4p, or Trm4p, on termination readthrough and +1 frameshift
      events. To this end, we have transformed each of the yeast deletion strains with
      a lacZ-luc dual-reporter vector harboring selected programmed recoding sites. We
      have found that only deletion of the PUS3 gene, encoding the enzyme that
      introduces pseudouridines at position 38 or 39 in tRNA, has an effect on the
      efficiency of the translation process. In this mutant, we have observed a reduced
      readthrough efficiency of each stop codon by natural nonsense suppressor tRNAs.
      This effect is solely due to the absence of pseudouridine 38 or 39 in tRNA
      because the inactive mutant protein Pus3[D151A]p did not restore the level of
      natural readthrough. Our results also show that absence of pseudouridine 39 in
      the slippery tRNA(UAG)(Leu) reduces +1 frameshift efficiency. Therefore, the
      presence of pseudouridine 38 or 39 in the tRNA anticodon arm enhances misreading
      of certain codons by natural nonsense tRNAs as well as promotes frameshifting on
      slippery sequences in yeast.

PMID- 12058041
TI  - Archaeal histone tetramerization determines DNA affinity and the direction of DNA
      supercoiling.
AB  - DNA binding and the topology of DNA have been determined in complexes formed by
      >20 archaeal histone variants and archaeal histone dimer fusions with residue
      replacements at sites responsible for histone fold dimer:dimer interactions.
      Almost all of these variants have decreased affinity for DNA. They have also lost
      the flexibility of the wild type archaeal histones to wrap DNA into a negative or
      positive supercoil depending on the salt environment; they wrap DNA into positive
      supercoils under all salt conditions. The histone folds of the archaeal histones,
      HMfA and HMfB, from Methanothermus fervidus are almost identical, but (HMfA)(2)
      and (HMfB)(2) homodimers assemble into tetramers with sequence-dependent
      differences in DNA affinity. By construction and mutagenesis of HMfA+HMfB and
      HMfB+HMfA histone dimer fusions, the structure formed at the histone dimer:dimer
      interface within an archaeal histone tetramer has been shown to determine this
      difference in DNA affinity. Therefore, by regulating the assembly of different
      archaeal histone dimers into tetramers that have different sequence affinities,
      the assembly of archaeal histone-DNA complexes could be localized and used to
      regulate gene expression.

PMID- 12058042
TI  - Peroxynitrite stimulates L-arginine transport system y(+) in glial cells. A
      potential mechanism for replenishing neuronal L-arginine.
AB  - We have reported previously that peroxynitrite stimulates L-arginine release from
      astrocytes, but the mechanism responsible for such an effect remains elusive. To
      explore this issue, we studied the regulation of L-[(3)H]arginine transport by
      either exogenous or endogenous peroxynitrite in glial cells. A 2-fold
      peroxynitrite-mediated stimulation of l-arginine release in C6 cells was found to
      be Na(+)-independent, was prevented by 5 mm L-arginine and, although only in the
      presence of Na(+), was blocked by 5 mm L-alanine or L-leucine. Peroxynitrite
      mediated stimulation of L-arginine uptake was trans-stimulated by 10 mm L
      arginine and was inhibited in a dose-dependent fashion (k(i) of approximately 40
      microm) by the system y(+) inhibitor N-ethylmaleimide in C6 cells. Endogenous
      production of peroxynitrite in lipopolysaccharide-treated astrocytes triggered an
      increased L-arginine transport activity without affecting Cat1 l-arginine
      transporter mRNA levels. However, Western blot analyses of peroxynitrite-treated
      astrocytes and C6 glial cells revealed a 3-nitrotyrosinated anti-Cat1
      immunopositive band, strongly suggesting peroxynitrite-mediated Cat1 nitration.
      Furthermore, peroxynitrite stimulation of L-arginine release was abolished in
      fibroblast cells homozygous for a targeted inactivation of the Cat1 gene.
      Finally, peroxynitrite-triggered L-arginine released from astrocytes was
      efficiently taken up by neurons in an insert-based co-culture system. These
      results strongly suggest that peroxynitrite-mediated activation of the Cat1
      transporter in glial cells may serve as a mechanism focused to replenish L
      arginine in the neighboring neurons.

PMID- 12058043
TI  - Leptin activates cardiac fatty acid oxidation independent of changes in the AMP
      activated protein kinase-acetyl-CoA carboxylase-malonyl-CoA axis.
AB  - Leptin regulates fatty acid metabolism in liver, skeletal muscle, and pancreas by
      partitioning fatty acids into oxidation rather than triacylglycerol (TG) storage.
      Although leptin receptors are present in the heart, it is not known whether
      leptin also regulates cardiac fatty acid metabolism. To determine whether leptin
      directly regulates cardiac fatty acid metabolism, isolated working rat hearts
      were perfused with 0.8 mm [9,10-(3)H]palmitate and 5 mm [1-(14)C]glucose to
      measure palmitate and glucose oxidation rates. Leptin (60 ng/ml) significantly
      increased palmitate oxidation rates 60% above control hearts (p < 0.05) and
      decreased TG content by 33% (p < 0.05) over the 60-min perfusion period. In
      contrast, there was no difference in glucose oxidation rates between leptin
      treated and control hearts. Although leptin did not affect cardiac work, oxygen
      consumption increased by 30% (p < 0.05) and cardiac efficiency was decreased by
      42% (p < 0.05). AMP-activated protein kinase (AMPK) plays a major role in the
      regulation of cardiac fatty acid oxidation by inhibiting acetyl-CoA carboxylase
      (ACC) and reducing malonyl-CoA levels. Leptin has also been shown to increase
      fatty acid oxidation in skeletal muscle through the activation of AMPK. However,
      we demonstrate that leptin had no significant effect on AMPK activity, AMPK
      phosphorylation state, ACC activity, or malonyl-CoA levels. AMPK activity and its
      phosphorylation state were also unaffected after 5 and 10 min of perfusion in the
      presence of leptin. The addition of insulin (100 microunits/ml) to the perfusate
      reduced the ability of leptin to increase fatty acid oxidation and decrease
      cardiac TG content. These data demonstrate for the first time that leptin
      activates fatty acid oxidation and decreases TG content in the heart. We also
      show that the effects of leptin in the heart are independent of changes in the
      AMPK-ACC-malonyl-CoA axis.

PMID- 12058044
TI  - Mechanism of Galpha i-mediated inhibition of type V adenylyl cyclase.
AB  - The topology of mammalian adenylyl cyclase reveals an integral membrane protein
      composed of an alternating series of membrane and cytoplasmic domains (C1 and
      C2). The stimulatory G protein, Galpha(s), binds within a cleft in the C2 domain
      of adenylyl cyclase while Galpha(i) binds within the opposite cleft in the C1
      domain. The mechanism of these two regulators also appears to be in opposition.
      Activation of adenylyl cyclase by Galpha(s) or forskolin results in a 100-fold
      increase in the apparent affinity of the two domains for one another. We show
      herein that Galpha(i) reduces C1/C2 domain interaction and thus formation of the
      adenylyl cyclase catalytic site. Mutants that increase the affinity of C1 for C2
      decrease the ability of Galpha(i) to inhibit the enzyme. In addition, Galpha(i)
      can influence binding of molecules to the catalytic site, which resides at the
      C1/C2 interface. Adenylyl cyclase can bind substrate analogs in the presence of
      Galpha(i) but cannot simultaneously bind Galpha(i) and transition state analogs
      such as 2'd3'-AMP. Galpha(i) also cannot inhibit the membrane-bound enzyme in the
      presence of manganese, which increases the affinity of adenylyl cyclase for ATP
      and substrate analogs. Thus homologous G protein alpha-subunits promote
      bidirectional regulation at the domain interface of the pseudosymmetrical
      adenylyl cyclase enzyme.

PMID- 12058045
TI  - Residues in the first extracellular loop of a G protein-coupled receptor play a
      role in signal transduction.
AB  - The Saccharomyces cerevisiae pheromone, alpha-factor (WHWLQLKPGQPMY), and Ste2p,
      its G protein-coupled receptor, were used as a model system to study ligand
      receptor interaction. Cys-scanning mutagenesis on each residue of EL1, the first
      extracellular loop of Ste2p, was used to generate a library of 36 mutants with a
      single Cys residue substitution. Mutation of most residues of EL1 had only
      negligible effects on ligand affinity and biological activity of the mutant
      receptors. However, five mutants were identified that were either partially
      (L102C and T114C) or severely (N105C, S108C, and Y111C) compromised in signaling
      but retained binding affinities similar to those of wild-type receptor. Three
      dimensional modeling, secondary structure predictions, and subsequent circular
      dichroism studies on a synthetic peptide with amino acid sequence corresponding
      to EL1 suggested the presence of a helix corresponding to EL1 residues 106 to 114
      followed by two short beta-strands (residues 126 to 135). The distinctive
      periodicity of the five residues with a signal-deficient phenotype combined with
      biophysical studies suggested a functional involvement in receptor activation of
      a face on a 3(10) helix in this region of EL1. These studies indicate that EL1
      plays an important role in the conformational switch that activates the Ste2p
      receptor to initiate the mating pheromone signal transduction pathway.

PMID- 12058046
TI  - The structural bases of antibiotic resistance in the clinically derived mutant
      beta-lactamases TEM-30, TEM-32, and TEM-34.
AB  - Widespread use of beta-lactam antibiotics has promoted the evolution of beta
      lactamase mutant enzymes that can hydrolyze ever newer classes of these drugs.
      Among the most pernicious mutants are the inhibitor-resistant TEM beta-lactamases
      (IRTs), which elude mechanism-based inhibitors, such as clavulanate. Despite much
      research on these IRTs, little is known about the structural bases of their
      action. This has made it difficult to understand how many of the resistance
      substitutions act as they often occur far from Ser-130. Here, three IRT
      structures, TEM-30 (R244S), TEM-32 (M69I/M182T), and TEM-34 (M69V), are
      determined by x-ray crystallography at 2.00, 1.61, and 1.52 A, respectively. In
      TEM-30, the Arg-244 --> Ser substitution (7.8 A from Ser-130) displaces a
      conserved water molecule that usually interacts with the beta-lactam C3
      carboxylate. In TEM-32, the substitution Met-69 --> Ile (10 A from Ser-130)
      appears to distort Ser-70, which in turn causes Ser-130 to adopt a new
      conformation, moving its O gamma further away, 2.3 A from where the inhibitor
      would bind. This substitution also destabilizes the enzyme by 1.3 kcal/mol. The
      Met-182 --> Thr substitution (20 A from Ser-130) has no effect on enzyme activity
      but rather restabilizes the enzyme by 2.9 kcal/mol. In TEM-34, the Met-69 --> Val
      substitution similarly leads to a conformational change in Ser-130, this time
      causing it to hydrogen bond with Lys-73 and Lys-234. This masks the lone pair
      electrons of Ser-130 O gamma, reducing its nucleophilicity for cross-linking. In
      these three structures, distant substitutions result in accommodations that
      converge on the same point of action, the local environment of Ser-130.

PMID- 12058047
TI  - Bestrophin interacts physically and functionally with protein phosphatase 2A.
AB  - Bestrophin is a 68-kDa basolateral plasma membrane protein expressed in retinal
      pigment epithelial cells (RPE). It is encoded by the VMD2 gene, which is mutated
      in Best macular dystrophy, a disease characterized by a depressed light peak in
      the electrooculogram. Recently it was proposed that bestrophin is a chloride
      channel responsible for generating the light peak. To investigate its function
      further, we immunoaffinity purified a bestrophin complex from RPE lysates and
      identified bestrophin and the beta-catalytic subunit of protein phosphatase 2A
      (PP2A) as members of the complex by matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry. Protein-protein interaction between bestrophin
      and PP2Ac and the structural subunit of PP2A, PR65, was confirmed by reciprocal
      immunoprecipitation. The C-terminal cytoplasmic domain of bestrophin was
      sufficient for the interaction with PP2A as demonstrated by a pulldown assay
      using a fusion of this domain with glutathione S-transferase. Bestrophin was
      phosphorylated when expressed in RPE-J cells and this phosphorylation was
      sensitive to okadaic acid. Purified PP2A effectively dephosphorylated bestrophin
      in vitro. These data suggest that bestrophin is in the signal transduction
      pathway that modulates the light peak of the electrooculogram, that it is
      regulated by phosphorylation, and that phosphorylation of bestrophin is in turn
      regulated by PP2A.

PMID- 12058048
TI  - Determination of the glycosaminoglycan-protein linkage region oligosaccharide
      structures of proteoglycans from Drosophila melanogaster and Caenorhabditis
      elegans.
AB  - Caenorhabditis elegans and Drosophila melanogaster are relevant models for
      studying the roles of glycosaminoglycans (GAG) during the development of
      multicellular organisms. The genome projects of these organisms have revealed the
      existence of multiple genes related to GAG-synthesizing enzymes. Although the
      putative genes encoding the enzymes that synthesize the GAG-protein linkage
      region have also been identified, there is no direct evidence that the GAG chains
      bind covalently to core proteins. This study aimed to clarify whether GAG chains
      in these organisms are linked to core proteins through the conventional linkage
      region tetrasaccharide sequence found in vertebrates and whether modifications by
      phosphorylation and sulfation reported for vertebrates are present also in
      invertebrates. The linkage region oligosaccharides were isolated from C. elegans
      chondroitin in addition to D. melanogaster heparan and chondroitin sulfate after
      digestion with the respective bacterial eliminases and were then derivatized with
      a fluorophore 2-aminobenzamide. Their structures were characterized by gel
      filtration and anion-exchange high performance liquid chromatography in
      conjunction with enzymatic digestion and matrix-assisted laser desorption
      ionization time-of-flight spectrometry, which demonstrated a uniform linkage
      tetrasaccharide structure of -GlcUA-Gal-Gal-Xyl- or -GlcUA-Gal-Gal-Xyl(2-O
      phosphate)- for C. elegans chondroitin and D. melanogaster CS, respectively. In
      contrast, the unmodified and phosphorylated counterparts were demonstrated in
      heparan sulfate of adult flies at a molar ratio of 73:27, and in that of the
      immortalized D. melanogaster S2 cell line at a molar ratio of 7:93, which
      suggests that the linkage region in the fruit fly first becomes phosphorylated
      uniformly on the Xyl residue and then dephosphorylated. It has been established
      here that GAG chains in both C. elegans and D. melanogaster are synthesized on
      the core protein through the ubiquitous linkage region tetrasaccharide sequence,
      suggesting that indispensable functions of the linkage region in the GAG
      synthesis have been well conserved during evolution.

PMID- 12058049
TI  - Sexual signaling on a cellular level: lessons from plant reproduction.

PMID- 12058050
TI  - ER-golgi traffic is a prerequisite for efficient ER degradation.
AB  - Protein quality control is an essential function of the endoplasmic reticulum.
      Misfolded proteins unable to acquire their native conformation are retained in
      the endoplasmic reticulum, retro-translocated back into the cytosol, and degraded
      via the ubiquitin-proteasome system. We show that efficient degradation of
      soluble malfolded proteins in yeast requires a fully competent early secretory
      pathway. Mutations in proteins essential for ER-Golgi protein traffic severely
      inhibit ER degradation of the model substrate CPY*. We found ER localization of
      CPY* in WT cells, but no other specific organelle for ER degradation could be
      identified by electron microscopy studies. Because CPY* is degraded in COPI coat
      mutants, only a minor fraction of CPY* or of a proteinaceous factor required for
      degradation seems to enter the recycling pathway between ER and Golgi. Therefore,
      we propose that the disorganized structure of the ER and/or the mislocalization
      of Kar2p, observed in early secretory mutants, is responsible for the reduction
      in CPY* degradation. Further, we observed that mutations in proteins directly
      involved in degradation of malfolded proteins (Der1p, Der3/Hrd1p, and Hrd3p) lead
      to morphological changes of the endoplasmic reticulum and the Golgi, escape of
      CPY* into the secretory pathway and a slower maturation rate of wild-type CPY.

PMID- 12058051
TI  - The small GTPase Rab13 regulates assembly of functional tight junctions in
      epithelial cells.
AB  - Junctional complexes such as tight junctions (TJ) and adherens junctions are
      required for maintaining cell surface asymmetry and polarized transport in
      epithelial cells. We have shown that Rab13 is recruited to junctional complexes
      from a cytosolic pool after cell-cell contact formation. In this study, we
      investigate the role of Rab13 in modulating TJ structure and functions in
      epithelial MDCK cells. We generate stable MDCK cell lines expressing inactive
      (T22N mutant) and constitutively active (Q67L mutant) Rab13 as GFP-Rab13
      chimeras. Expression of GFP-Rab13Q67L delayed the formation of electrically tight
      epithelial monolayers as monitored by transepithelial electrical resistance (TER)
      and induced the leakage of small nonionic tracers from the apical domain. It also
      disrupted the TJ fence diffusion barrier. Freeze-fracture EM analysis revealed
      that tight junctional structures did not form a continuous belt but rather a
      discontinuous series of stranded clusters. Immunofluorescence studies showed that
      the expression of Rab13Q67L delayed the localization of the TJ transmembrane
      protein, claudin1, at the cell surface. In contrast, the inactive Rab13T22N
      mutant did not disrupt TJ functions, TJ strand architecture nor claudin1
      localization. Our data revealed that Rab13 plays an important role in regulating
      both the structure and function of tight junctions.

PMID- 12058052
TI  - Kinesin-like protein CHO1 is required for the formation of midbody matrix and the
      completion of cytokinesis in mammalian cells.
AB  - CHO1 is a mammalian kinesin-like motor protein of the MKLP1 subfamily. It
      associates with the spindle midzone during anaphase and concentrates to a midbody
      matrix during cytokinesis. CHO1 was originally implicated in karyokinesis, but
      the invertebrate homologues of CHO1 were shown to function in the midzone
      formation and cytokinesis. To analyze the role of the protein in mammalian cells,
      we mutated the ATP-binding site of CHO1 and expressed it in CHO cells. Mutant
      protein (CHO1F') was able to interact with microtubules via ATP-independent
      microtubule-binding site(s) but failed to accumulate at the midline of the
      central spindle and affected the localization of endogenous CHO1. Although the
      segregation of chromosomes, the bundling of midzone microtubules, and the
      initiation of cytokinesis proceeded normally in CHO1F'-expressing cells, the
      completion of cytokinesis was inhibited. Daughter cells were frequently entering
      interphase while connected by a microtubule-containing cytoplasmic bridge from
      which the dense midbody matrix was missing. Depletion of endogenous CHO1 via RNA
      mediated interference also affected the formation of midbody matrix in dividing
      cells, caused the disorganization of midzone microtubules, and resulted in
      abortive cytokinesis. Thus, CHO1 may not be required for karyokinesis, but it is
      essential for the proper midzone/midbody formation and cytokinesis in mammalian
      cells.

PMID- 12058054
TI  - Type II keratins are phosphorylated on a unique motif during stress and mitosis
      in tissues and cultured cells.
AB  - Epithelial cell keratins make up the type I (K9-K20) and type II (K1-K8)
      intermediate filament proteins. In glandular epithelia, K8 becomes phosphorylated
      on S73 ((71)LLpSPL) in human cultured cells and tissues during stress, apoptosis,
      and mitosis. Of all known proteins, the context of the K8 S73 motif (LLS/TPL) is
      unique to type II keratins and is conserved in epidermal K5/K6, esophageal K4,
      and type II hair keratins, except that serine is replaced by threonine. Because
      knowledge regarding epidermal and esophageal keratin regulation is limited, we
      tested whether K4-K6 are phosphorylated on the LLTPL motif. K5 and K6 become
      phosphorylated in vitro on threonine by the stress-activated kinase p38. Site
      specific anti-phosphokeratin antibodies to LLpTPL were generated, which
      demonstrated negligible basal K4-K6 phosphorylation. In contrast, treatment of
      primary keratinocytes and other cultured cells, and ex vivo skin and esophagus
      cultures, with serine/threonine phosphatase inhibitors causes a dramatic increase
      in K4-K6 LLpTPL phosphorylation. This phosphorylation is accompanied by keratin
      solubilization, filament reorganization, and collapse. K5/K6 LLTPL
      phosphorylation occurs in vivo during mitosis and apoptosis induced by UV light
      or anisomycin, and in human psoriatic skin and squamous cell carcinoma. In
      conclusion, type II keratins of proliferating epithelia undergo phosphorylation
      at a unique and conserved motif as part of physiological mitotic and stress
      related signals.

PMID- 12058055
TI  - Centrosome reorientation in wound-edge cells is cell type specific.
AB  - The reorientation of the microtubule organizing center during cell migration into
      a wound in the monolayer was directly observed in living wound-edge cells
      expressing gamma-tubulin tagged with green fluorescent protein. Our results
      demonstrate that in CHO cells, the centrosome reorients to a position in front of
      the nucleus, toward the wound edge, whereas in PtK cells, the centrosome lags
      behind the nucleus during migration into the wound. In CHO cells, the average
      rate of centrosome motion was faster than that of the nucleus; the converse was
      true in PtK cells. In both cell lines, centrosome motion was stochastic, with
      periods of rapid motion interspersed with periods of slower motion. Centrosome
      reorientation in CHO cells required dynamic microtubules and cytoplasmic
      dynein/dynactin activity and could be prevented by altering cell-to-cell or cell
      to-substrate adhesion. Microtubule marking experiments using photoactivation of
      caged tubulin demonstrate that microtubules are transported in the direction of
      cell motility in both cell lines but that in PtK cells, microtubules move
      individually, whereas their movement is more coherent in CHO cells. Our data
      demonstrate that centrosome reorientation is not required for directed migration
      and that diverse cells use distinct mechanisms for remodeling the microtubule
      array during directed migration.

PMID- 12058053
TI  - The cytoplasmic tail of invariant chain regulates endosome fusion and morphology.
AB  - The major histocompatibility complex class II associated invariant chain (Ii) has
      been shown to inhibit endocytic transport and to increase the size of endosomes.
      We have recently found that this property has a significant impact on antigen
      processing and presentation. Here, we show in a cell-free endosome fusion assay
      that expression of Ii can increase fusion after phosphatidylinositol 3-kinase
      activity is blocked by wortmannin. In live cells wortmannin was also not able to
      block formation of the Ii-induced enlarged endosomes. The effects of Ii on
      endosomal transport and morphology depend on elements within the cytoplasmic
      tail. Data from mutagenesis analysis and nuclear magnetic resonance-based
      structure calculations of the Ii cytoplasmic tail demonstrate that free negative
      charges that are not involved in internal salt bridges are essential for both
      interactions between the tails and for the formation of enlarged endosomes. This
      correlation indicates that it is interactions between the Ii cytoplasmic tails
      that are involved in endosome fusion. The combined data from live cells, cell
      free assays, and molecular dynamic simulations suggest that Ii molecules on
      different vesicles can promote endosome docking and fusion and thereby control
      endosomal traffic of membrane proteins and endosomal content.

PMID- 12058056
TI  - Stu1p is physically associated with beta-tubulin and is required for structural
      integrity of the mitotic spindle.
AB  - Formation of the bipolar mitotic spindle relies on a balance of forces acting on
      the spindle poles. The primary outward force is generated by the kinesin-related
      proteins of the BimC family that cross-link antiparallel interpolar microtubules
      and slide them past each other. Here, we provide evidence that Stu1p is also
      required for the production of this outward force in the yeast Saccharomyces
      cerevisiae. In the temperature-sensitive stu1-5 mutant, spindle pole separation
      is inhibited, and preanaphase spindles collapse, with their previously separated
      poles being drawn together. The temperature sensitivity of stu1-5 can be
      suppressed by doubling the dosage of Cin8p, a yeast BimC kinesin-related protein.
      Stu1p was observed to be a component of the mitotic spindle localizing to the
      midregion of anaphase spindles. It also binds to microtubules in vitro, and we
      have examined the nature of this interaction. We show that Stu1p interacts
      specifically with beta-tubulin and identify the domains required for this
      interaction on both Stu1p and beta-tubulin. Taken together, these findings
      suggest that Stu1p binds to interpolar microtubules of the mitotic spindle and
      plays an essential role in their ability to provide an outward force on the
      spindle poles.

PMID- 12058057
TI  - Thrombospondin 2 inhibits microvascular endothelial cell proliferation by a
      caspase-independent mechanism.
AB  - The matricellular protein thrombospondin 2 (TSP2) regulates a variety of cell
      matrix interactions. A prominent feature of TSP2-null mice is increased
      microvascular density, particularly in connective tissues synthesized after
      injury. We investigated the cellular basis for the regulation of angiogenesis by
      TSP2 in cultures of murine and human fibroblasts and endothelial cells.
      Fibroblasts isolated from murine and human dermis synthesize TSP2 mRNA and
      secrete significant amounts of immunoreactive TSP2, whereas endothelial cells
      from mouse lung and human dermis did not synthesize TSP2 mRNA or protein.
      Recombinant mouse TSP2 inhibited growth of human microvascular endothelial cells
      (HMVECs) mediated by basic fibroblast growth factor, insulin-like growth factor
      1, epidermal growth factor, and vascular endothelial growth factor (VEGF). HMVECs
      exposed to TSP2 in the presence of these growth factors had a decreased
      proportion of cells in S and G2/M phases. HMVECs cultured with a combination of
      basic fibroblast growth factor, insulin-like growth factor-1, and epidermal
      growth factor displayed an increased proportion of nonviable cells in the
      presence of TSP2, but the addition of VEGF blocked this TSP2-mediated impairment
      of cell viability. TSP2-mediated inhibition of DNA synthesis by HMVECs in the
      presence of VEGF was not affected by the broad-spectrum caspase inhibitor zVAD
      fmk. Similar findings were obtained with TSP1. Taken together, these observations
      indicate that either TSP2 or TSP1 can inhibit HMVEC proliferation by inhibition
      of cell cycle progression and induction of cell death, but the mechanisms
      responsible for TSP2-mediated inhibition of cell cycle progression are
      independent from those leading to cell death.

PMID- 12058058
TI  - Pancreatic beta-cell protein granuphilin binds Rab3 and Munc-18 and controls
      exocytosis.
AB  - Granuphilin/Slp-4 is a member of the synaptotagmin-like protein family expressed
      in pancreatic beta-cells and in the pituitary gland. We show by confocal
      microscopy that both granuphilin-a and -b colocalize with insulin-containing
      secretory granules positioned at the periphery of pancreatic beta-cells.
      Overexpression of granuphilins in insulin-secreting cell lines caused a profound
      inhibition of stimulus-induced exocytosis. Granuphilins were found to bind to two
      components of the secretory machinery of pancreatic beta-cells, the small GTP
      binding protein Rab3 and the soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE)-binding protein Munc-18. The interaction with Rab3
      occurred only with the GTP-bound form of the protein and was prevented by a point
      mutation in the effector domain of the GTPase. Structure-function studies using
      granuphilin-b mutants revealed that complete loss of Rab3 binding is associated
      with a reduction in the capacity to inhibit exocytosis. However, the
      granuphilin/Rab3 complex alone is not sufficient to mediate the decrease of
      exocytosis, suggesting the existence of additional binding partners. Taken
      together, our observations indicate that granuphilins play an important role in
      pancreatic beta-cell exocytosis. In view of the postulated role of Munc-18 in
      secretory vesicle docking, our data suggest that granuphilins may also be
      involved in this process.

PMID- 12058060
TI  - Gene expression patterns in human liver cancers.
AB  - Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. Using cDNA
      microarrays to characterize patterns of gene expression in HCC, we found
      consistent differences between the expression patterns in HCC compared with those
      seen in nontumor liver tissues. The expression patterns in HCC were also readily
      distinguished from those associated with tumors metastatic to liver. The global
      gene expression patterns intrinsic to each tumor were sufficiently distinctive
      that multiple tumor nodules from the same patient could usually be recognized and
      distinguished from all the others in the large sample set on the basis of their
      gene expression patterns alone. The distinctive gene expression patterns are
      characteristic of the tumors and not the patient; the expression programs seen in
      clonally independent tumor nodules in the same patient were no more similar than
      those in tumors from different patients. Moreover, clonally related tumor masses
      that showed distinct expression profiles were also distinguished by genotypic
      differences. Some features of the gene expression patterns were associated with
      specific phenotypic and genotypic characteristics of the tumors, including growth
      rate, vascular invasion, and p53 overexpression.

PMID- 12058061
TI  - p38 Mitogen-activated protein kinase-, calcium-calmodulin-dependent protein
      kinase-, and calcineurin-mediated signaling pathways transcriptionally regulate
      myogenin expression.
AB  - In this report, we identify myogenin as an important transcriptional target under
      the control of three intracellular signaling pathways, namely, the p38 mitogen
      activated protein kinase- (MAPK), calcium-calmodulin-dependent protein kinase-
      (CaMK), and calcineurin-mediated pathways, during skeletal muscle
      differentiation. Three cis-elements (i.e., the E box, myocyte enhancer factor
      [MEF] 2, and MEF3 sites) in the proximal myogenin promoter in response to these
      three pathways are defined. MyoD, MEF2s, and Six proteins, the trans-activators
      bound to these cis-elements, are shown to be activated by these signaling
      pathways. Our data support a model in which all three signaling pathways act in
      parallel but nonredundantly to control myogenin expression. Inhibition of any one
      pathway will result in abolished or reduced myogenin expression and subsequent
      phenotypic differentiation. In addition, we demonstrate that CaMK and calcineurin
      fail to activate MEF2s in Rhabdomyosarcoma-derived RD cells. For CaMK, we show
      its activation in response to differentiation signals and its effect on the
      cytoplasmic translocation of histone deacetylases 5 are not compromised in RD
      cells, suggesting histone deacetylases 5 cytoplasmic translocation is necessary
      but not sufficient, and additional signal is required in conjunction with CaMK to
      activate MEF2 proteins.

PMID- 12058059
TI  - Null mutation of AtCUL1 causes arrest in early embryogenesis in Arabidopsis.
AB  - The SCF (for SKP1, Cullin/CDC53, F-box protein) ubiquitin ligase targets a number
      of cell cycle regulators, transcription factors, and other proteins for
      degradation in yeast and mammalian cells. Recent genetic studies demonstrate that
      plant F-box proteins are involved in auxin responses, jasmonate signaling, flower
      morphogenesis, photocontrol of circadian clocks, and leaf senescence, implying a
      large spectrum of functions for the SCF pathway in plant development. Here, we
      present a molecular and functional characterization of plant cullins. The
      Arabidopsis genome contains 11 cullin-related genes. Complementation assays
      revealed that AtCUL1 but not AtCUL4 can functionally complement the yeast cdc53
      mutant. Arabidopsis mutants containing transfer DNA (T-DNA) insertions in the
      AtCUL1 gene were shown to display an arrest in early embryogenesis. Consistently,
      both the transcript and the protein of the AtCUL1 gene were found to accumulate
      in embryos. The AtCUL1 protein localized mainly in the nucleus but also weakly in
      the cytoplasm during interphase and colocalized with the mitotic spindle in
      metaphase. Our results demonstrate a critical role for the SCF ubiquitin ligase
      in Arabidopsis embryogenesis.

PMID- 12058062
TI  - Pink-eyed dilution protein controls the processing of tyrosinase.
AB  - The processing of tyrosinase, which catalyzes the limiting reaction in melanin
      synthesis, was investigated in melan-p1 melanocytes, which are null at the p
      locus. Endoglycosidase H digestion showed that a significant fraction of
      tyrosinase was retained in the endoplasmic reticulum. This retention could be
      rescued either by transfection of melan-p1 cells with an epitope-tagged wild-type
      p transcript or by treatment with either bafilomycin A1 or ammonium chloride. We
      found that the endoplasmic reticulum contains a significant amount of p protein,
      thus supporting a role for p within this compartment. Using immunofluoresence, we
      showed that most mature full-length tyrosinase in melan-p1 cells was located in
      the perinuclear area near the Golgi, in contrast to its punctate melanosomal
      pattern in wild-type melanocytes. Expression of p in melan-p1 cells restored
      tyrosinase to melanosomes. Triton X-114 phase separation revealed that an
      increased amount of tyrosinase was proteolyzed in melan-p1 cells compared with
      wild-type melanocytes. The proteolyzed tyrosinase was no longer membrane bound,
      but remained enzymatically active and a large proportion was secreted into the
      culture medium of melan-p1 cells. We conclude that p regulates posttranslational
      processing of tyrosinase, and hypopigmentation in melan-p1 cells is the result of
      altered tyrosinase processing and trafficking.

PMID- 12058063
TI  - Down-regulation of protease-activated receptor-1 is regulated by sorting nexin 1.
AB  - Degradation or "down-regulation" of protease-activated receptor-1 (PAR1), a G
      protein-coupled receptor for thrombin, is critical for termination of receptor
      signaling. Toward understanding the molecular mechanisms by which activated PAR1
      is internalized, sorted to lysosomes, and degraded, we investigated whether PAR1
      interacted with sorting nexin 1 (SNX1). SNX1 is a membrane-associated protein
      that functions in lysosomal sorting of the epidermal growth factor receptor. In
      vitro biochemical binding assays revealed a specific interaction between a
      glutathione S-transferase fusion of SNX1 and PAR1. In HeLa cells, activated PAR1
      colocalized with endogenous SNX1 and coimmunoprecipitated SNX1. SNX1 contains a
      phox homology domain predicted to bind phosphatidylinositol-3-phosphate and a C
      terminal coiled-coil region. To assess SNX1 function, we examined the effects of
      SNX1 deletion mutants on PAR1 trafficking. Neither the N terminus nor phox
      homology domain of SNX1 affected PAR1 trafficking. By contrast, overexpression of
      SNX1 C-terminal domain markedly inhibited agonist-induced degradation of PAR1,
      whereas internalization remained virtually intact. Immunofluorescence microscopy
      studies revealed substantial PAR1 accumulation in an early endosome antigen-1
      positive compartment in agonist-treated cells expressing SNX1 C terminus. By
      contrast, lysosome-associated membrane protein-1 distribution was unperturbed.
      Together, these findings strongly suggest a role for SNX1 in sorting of PAR1 from
      early endosomes to lysosomes. Moreover, this study provides the first example of
      a protein involved in lysosomal sorting of a G protein-coupled receptor in
      mammalian cells.

PMID- 12058065
TI  - Recruitment of dioxin receptor to active transcription sites.
AB  - The aryl hydrocarbon receptor (AhR or dioxin receptor) is a ligand-activated
      transcription factor that heterodimerizes with the AhR nuclear translocator
      (ARNT/HIF-1beta) to form an AhR/ARNT transcription factor complex. This complex
      binds to specific DNA sites in the regulatory domains of numerous target genes
      and mediates the biological effects of exogenous ligands. Herein, we have
      investigated the subcellular distribution of the AhR/ARNT complex in response to
      ligand stimulation, by using live-cell confocal and high-resolution deconvolution
      microscopy. We found that unliganded AhR shows a predominantly cytoplasmic
      diffuse distribution in mouse hepatoma cells. On addition of ligand, AhR rapidly
      translocates to the nucleus and accumulates in multiple bright foci. Inhibition
      of transcription prevented the formation of AhR foci. Dual- and triple
      immunolabeling experiments, combined with labeling of nascent RNA, showed that
      the foci are transcription sites, indicating that upon ligand stimulation, AhR is
      recruited to active transcription sites. The interaction of AhR with ARNT was
      both necessary and sufficient for the recruitment of AhR to transcription sites.
      These results indicate that AhR/ARNT complexes are recruited to specific
      subnuclear compartments in a ligand-dependent manner and that these foci
      represent the sites of AhR target genes.

PMID- 12058064
TI  - Identification of genes periodically expressed in the human cell cycle and their
      expression in tumors.
AB  - The genome-wide program of gene expression during the cell division cycle in a
      human cancer cell line (HeLa) was characterized using cDNA microarrays.
      Transcripts of >850 genes showed periodic variation during the cell cycle.
      Hierarchical clustering of the expression patterns revealed coexpressed groups of
      previously well-characterized genes involved in essential cell cycle processes
      such as DNA replication, chromosome segregation, and cell adhesion along with
      genes of uncharacterized function. Most of the genes whose expression had
      previously been reported to correlate with the proliferative state of tumors were
      found herein also to be periodically expressed during the HeLa cell cycle.
      However, some of the genes periodically expressed in the HeLa cell cycle do not
      have a consistent correlation with tumor proliferation. Cell cycle-regulated
      transcripts of genes involved in fundamental processes such as DNA replication
      and chromosome segregation seem to be more highly expressed in proliferative
      tumors simply because they contain more cycling cells. The data in this report
      provide a comprehensive catalog of cell cycle regulated genes that can serve as a
      starting point for functional discovery. The full dataset is available at
      http://genome-www.stanford.edu/Human-CellCycle/HeLa/.

PMID- 12058066
TI  - The RNA binding activity of a ribosome biogenesis factor, nucleophosmin/B23, is
      modulated by phosphorylation with a cell cycle-dependent kinase and by
      association with its subtype.
AB  - Nucleophosmin/B23 is a nucleolar phosphoprotein. It has been shown that B23 binds
      to nucleic acids, digests RNA, and is localized in nucleolar granular components
      from which preribosomal particles are transported to cytoplasm. The intracellular
      localization of B23 is significantly changed during the cell cycle. Here, we have
      examined the cellular localization of B23 proteins and the effect of mitotic
      phosphorylation of B23.1 on its RNA binding activity. Two splicing variants of
      B23 proteins, termed B23.1 and B23.2, were complexed both in vivo and in vitro.
      The RNA binding activity of B23.1 was impaired by hetero-oligomer formation with
      B23.2. Both subtypes of B23 proteins were phosphorylated during mitosis by cyclin
      B/cdc2. The RNA binding activity of B23.1 was repressed through cyclin B/cdc2
      mediated phosphorylation at specific sites in B23. Thus, the RNA binding activity
      of B23.1 is stringently modulated by its phosphorylation and subtype association.
      Interphase B23.1 was mainly localized in nucleoli, whereas B23.2 and mitotic
      B23.1, those of which were incapable of binding to RNA, were dispersed throughout
      the nucleoplasm and cytoplasm, respectively. These results suggest that nucleolar
      localization of B23.1 is mediated by its ability to associate with RNA.

PMID- 12058067
TI  - Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha
      converting enzyme at threonine 735: a potential role in regulated shedding.
AB  - The ectodomain of certain transmembrane proteins can be released by the action of
      cell surface proteases, termed secretases. Here we have investigated how mitogen
      activated protein kinases (MAPKs) control the shedding of membrane proteins. We
      show that extracellular signal-regulated kinase (Erk) acts as an intermediate in
      protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of
      the tumor necrosis factor alpha-converting enzyme (TACE) is phosphorylated by Erk
      at threonine 735. In addition, we show that Erk and TACE associate. This
      association is favored by Erk activation and by the presence of threonine 735. In
      contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in
      cells devoid of TACE activity, indicating that other proteases are also involved
      in TrkA shedding. These results demonstrate that secretases are able to
      discriminate between the different stimuli that trigger membrane protein
      ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the
      proteolytic function of membrane secretases.

PMID- 12058068
TI  - Subunit H of the V-ATPase involved in endocytosis shows homology to beta
      adaptins.
AB  - The vacuolar ATPase (V-ATPase) is a multisubunit enzyme that facilitates the
      acidification of intracellular compartments in eukaryotic cells and plays an
      important role in receptor-mediated endocytosis, intracellular trafficking
      processes, and protein degradation. In this study we show that the C-terminal
      fragment of 350 residues of the regulatory subunit H (V1H) of the V-ATPase shares
      structural and functional homologies with the beta-chains of adaptor protein
      complexes. Moreover, the fragment is similar to a region in the beta-subunit of
      COPI coatomer complexes, which suggests the existence of a shared domain in these
      three different families of proteins. For beta-adaptins, this fragment binds to
      cytoplasmic di-leucine-based sorting motifs such as in HIV-1 Nef that mediate
      endocytic trafficking. Expression of this fragment in cells blocks the
      internalization of transmembrane proteins, which depend on di-leucine-based
      motifs, whereas mutation of the consensus sequence GEY only partly diminishes the
      recognition of the sorting motif. Based on recent structural analysis, our
      results suggest that the di-leucine-binding domain consists of a HEAT or ARM
      repeat protein fold.

PMID- 12058069
TI  - Calmodulin regulates intracellular trafficking of epidermal growth factor
      receptor and the MAPK signaling pathway.
AB  - The epidermal growth factor receptor (EGFR) is a member of the tyrosine kinase
      receptor family involved in signal transduction and the regulation of cellular
      proliferation and differentiation. It is also a calmodulin-binding protein. To
      examine the role of calmodulin in the regulation of EGFR, the effect of
      calmodulin antagonist, W-13, on the intracellular trafficking of EGFR and the
      MAPK signaling pathway was analyzed. W-13 did not alter the internalization of
      EGFR but inhibited its recycling and degradation, thus causing the accumulation
      of EGF and EGFR in enlarged early endosomal structures. In addition, we
      demonstrated that W-13 stimulated the tyrosine phosphorylation of EGFR and
      consequent recruitment of Shc adaptor protein with EGFR, presumably through
      inhibition of the calmodulin-dependent protein kinase II (CaM kinase II). W-13
      mediated EGFR phosphorylation was blocked by metalloprotease inhibitor, BB94,
      indicating a possible involvement of shedding in this process. However, MAPK
      activity was decreased by W-13; dissection of this signaling pathway showed that
      W-13 specifically interferes with Raf-1 activity. These data are consistent with
      the regulation of EGFR by calmodulin at several steps of the receptor signaling
      and trafficking pathways.

PMID- 12058070
TI  - Human chromosomes 9, 12, and 15 contain the nucleation sites of stress-induced
      nuclear bodies.
AB  - We previously reported the identification of a novel nuclear compartment
      detectable in heat-shocked HeLa cells that we termed stress-induced Src-activated
      during mitosis nuclear body (SNB). This structure is the recruitment center for
      heat shock factor 1 and for a number of RNA processing factors, among a subset of
      Serine-Arginine splicing factors. In this article, we show that stress-induced
      SNBs are detectable in human but not in hamster cells. By means of hamster>human
      cell hybrids, we have identified three human chromosomes (9, 12, and 15) that are
      individually able to direct the formation of stress bodies in hamster cells.
      Similarly to stress-induced SNB, these bodies are sites of accumulation of hnRNP
      A1-interacting protein and heat shock factor 1, are usually associated to
      nucleoli, and consist of clusters of perichromatin granules. We show that the p13
      q13 region of human chromosome 9 is sufficient to direct the formation of stress
      bodies in hamster>human cell hybrids. Fluorescence in situ hybridization
      experiments demonstrate that the pericentromeric heterochromatic q12 band of
      chromosome 9 and the centromeric regions of chromosomes 12 and 15 colocalize with
      stress-induced SNBs in human cells. Our data indicate that human chromosomes 9,
      12, and 15 contain the nucleation sites of stress bodies in heat-shocked HeLa
      cells.

PMID- 12058071
TI  - The G1/S cyclin Cig2p during meiosis in fission yeast.
AB  - Cyclin-dependent kinases (CDKs) are important for both mitotic and meiotic cell
      cycles. In fission yeast, the major CDK, Cdc2p is involved in premeiotic DNA
      replication and in meiosis II. One of its partners, the mitotic cyclin Cdc13p is
      known to be required for meiosis, whereas there are no studies on the G1/S cyclin
      Cig2p. In this article, we have studied the regulation of the Cdc2p/Cdc13p and
      Cdc2p/Cig2p complexes during synchronous meiosis. We observed that Cdc2p/Cig2p
      kinase is activated in an unexpected biphasic manner, first at onset of
      premeiotic S phase and again during meiotic nuclear divisions. The role of Cig2p
      during meiosis was investigated using cig2-deleted strains that exhibit delays in
      onset of both S phase and meiotic divisions as well as an inefficient completion
      of MII. Furthermore, analysis of cig2 transcripts revealed a meiosis-specific
      regulation of cig2 expression during MI/MII dependent upon the Mei4p
      transcription factor leading to a different transcription start site at this
      stage of meiosis.

PMID- 12058072
TI  - Cell cycle-dependent assembly of a Gin4-septin complex.
AB  - Gin4, a Nim1-related kinase, is required in budding yeast for localization of the
      septins and for proper control of daughter cell growth during G2/M. Gin4 becomes
      hyperphosphorylated when cells enter mitosis, leading to activation of Gin4
      kinase activity. In this study, we have used immunoaffinity chromatography to
      identify proteins that associate with Gin4 during mitosis, with the goal of
      finding targets of Gin4 kinase activity and proteins that play a role in Gin4
      activation. We show that during mitosis Gin4 is assembled into a multiprotein
      complex that includes Nap1, Bni5, the septins, and at least two molecules of
      Gin4. The associated Gin4 molecules present in this complex phosphorylate each
      other, leading to Gin4 hyperphosphorylation. Furthermore, the Shs1 septin present
      in the complex undergoes Gin4-dependent phosphorylation during mitosis and
      appears to be a substrate of Gin4 in vitro, suggesting that it is a target of
      Gin4 kinase activity in vivo. Genetic data support the idea that Shs1 is an
      important target of Gin4 kinase activity. Association of Gin4 with the septins
      during mitosis requires Shs1, Nap1, Cla4, Elm1, and the kinase activities of Gin4
      and Cdc28. Self-association of Gin4 molecules requires Shs1 but not Cla4 or Nap1.
      Previous work has suggested that the septins function together as a tight
      complex, and we found that the majority of the Shs1 in the cell is tightly bound
      to the other septins Cdc3, Cdc10, Cdc11, and Cdc12. Interestingly, however, Shs1
      can bind to Gin4 and induce Gin4 oligomerization under conditions in which the
      Cdc11 septin does not bind to Gin4, suggesting that Shs1 can function
      independently of the other septins. Taken together, these findings suggest that
      highly regulated protein-binding events ensure that the Gin4 kinase is activated
      only during mitosis and only in association with Shs1, a likely in vivo substrate
      of Gin4. In addition, these results provide clues to how Gin4 may regulate the
      localization or function of the septins.

PMID- 12058074
TI  - Dissociation of the tubulin dimer is extremely slow, thermodynamically very
      unfavorable, and reversible in the absence of an energy source.
AB  - The finding that exchange of tubulin subunits between tubulin dimers (alpha-beta
      + alpha'beta' <--> alpha'beta + alphabeta') does not occur in the absence of
      protein cofactors and GTP hydrolysis conflicts with the assumption that pure
      tubulin dimer and monomer are in rapid equilibrium. This assumption underlies the
      many physical chemical measurements of the K(d) for dimer dissociation. To
      resolve this discrepancy we used surface plasmon resonance to determine the rate
      constant for dimer dissociation. The half-time for dissociation was approximately
      9.6 h with tubulin-GTP, 2.4 h with tubulin-GDP, and 1.3 h in the absence of
      nucleotide. A Kd equal to 10(-11) M was calculated from the measured rate for
      dissociation and an estimated rate for association. Dimer dissociation was found
      to be reversible, and dimer formation does not require GTP hydrolysis or folding
      information from protein cofactors, because 0.2 microM tubulin-GDP incubated for
      20 h was eluted as dimer when analyzed by size exclusion chromatography. Because
      20 h corresponds to eight half-times for dissociation, only monomer would be
      present if dissociation were an irreversible reaction and if dimer formation
      required GTP or protein cofactors. Additional evidence for a 10(-11) M K(d) was
      obtained from gel exclusion chromatography studies of 0.02-2 nM tubulin-GDP. The
      slow dissociation of the tubulin dimer suggests that protein tubulin cofactors
      function to catalyze dimer dissociation, rather than dimer assembly. Assuming N
      site-GTP dissociation is from monomer, our results agree with the 16-h half-time
      for N-site GTP in vitro and 33 h half-life for tubulin N-site-GTP in CHO cells.

PMID- 12058073
TI  - Novel ATPase of SNF2-like protein family interacts with androgen receptor and
      modulates androgen-dependent transcription.
AB  - Nuclear receptors, including the androgen receptor (AR), regulate target cell
      transcription through interaction with auxiliary proteins to modify chromatin
      structure. We describe herein a novel AR-interacting protein, termed ARIP4, that
      has structural features typical of the SNF2-like protein family. With regard to
      the Snf2 domain, the closest homolog of ARIP4 is the ATRX protein. ARIP4 is a
      nuclear protein and comprises 1466 amino acids. It interacts with AR in vitro and
      in cultured yeast and mammalian cells. ARIP4 can be labeled with 8-azido-[gamma
      32P]ATP and exhibits DNA-dependent ATPase activity. Like several ATP-dependent
      chromatin remodeling proteins, ARIP4 generates superhelical torsion within linear
      DNA fragments in an ATP-dependent manner. With a stably integrated target
      promoter, ARIP4 elicits a modest enhancement of AR-dependent transactivation. In
      transient cotransfection assays, ARIP4 modulates AR function in a promoter
      dependent manner; it enhances receptor activity on minimal promoters, but does
      not activate more complex promoters. ARIP4 mutants devoid of ATPase activity fail
      to alter DNA topology and behave as trans-dominant negative regulators of AR
      function in transient assays.

PMID- 12058075
TI  - Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated
      epithelial morphogenesis.
AB  - The Gab family of docking proteins (Gab1 and Gab2) are phosphorylated in response
      to various cytokines and growth factors. Gab1 acts to diversify the signal
      downstream from the Met receptor tyrosine kinase through the recruitment of
      multiple signaling proteins, and is essential for epithelial morphogenesis. To
      determine whether Gab1 and Gab2 are functionally redundant, we have examined the
      role of Gab2 in epithelial cells. Both Gab1 and Gab2 are expressed in epithelial
      cells and localize to cell-cell junctions. However, whereas overexpression of
      Gab1 promotes a morphogenic response, the overexpression of Gab2 fails to induce
      this response. We show that Gab2 recruitment to the Met receptor is dependent on
      the Grb2 adapter protein. In contrast, Gab1 recruitment to Met is both Grb2
      dependent and Grb2 independent. The latter requires a novel amino acid sequence
      present in the Met-binding domain of Gab1 but not Gab2. Mutation of these
      residues in Gab1 impairs both association with the Met receptor and the ability
      of Gab1 to promote a morphogenic response, whereas their insertion into Gab2
      increases Gab2 association with Met, but does not confer on Gab2 the ability to
      promote epithelial morphogenesis. We propose that the Grb2-independent
      recruitment of Gab proteins to Met is necessary but not sufficient to promote
      epithelial morphogenesis.

PMID- 12058076
TI  - The association of ASAP1, an ADP ribosylation factor-GTPase activating protein,
      with focal adhesion kinase contributes to the process of focal adhesion assembly.
AB  - ASAP1 (ADP ribosylation factor [ARF]- GTPase-activating protein [GAP] containing
      SH3, ANK repeats, and PH domain) is a phospholipid-dependent ARF-GAP that binds
      to and is phosphorylated by pp60(Src). Using affinity chromatography and yeast
      two-hybrid interaction screens, we identified ASAP1 as a major binding partner of
      protein tyrosine kinase focal adhesion kinase (FAK). Glutathione S-transferase
      pull-down and coimmunoprecipitation assays showed the binding of ASAP1 to FAK is
      mediated by an interaction between the C-terminal SH3 domain of ASAP1 with the
      second proline-rich motif in the C-terminal region of FAK. Transient
      overexpression of wild-type ASAP1 significantly retarded the spreading of REF52
      cells plated on fibronectin. In contrast, overexpression of a truncated variant
      of ASAP1 that failed to bind FAK or a catalytically inactive variant of ASAP1
      lacking GAP activity resulted in a less pronounced inhibition of cell spreading.
      Transient overexpression of wild-type ASAP1 prevented the efficient organization
      of paxillin and FAK in focal adhesions during cell spreading, while failing to
      significantly alter vinculin localization and organization. We conclude from
      these studies that modulation of ARF activity by ASAP1 is important for the
      regulation of focal adhesion assembly and/or organization by influencing the
      mechanisms responsible for the recruitment and organization of selected focal
      adhesion proteins such as paxillin and FAK.

PMID- 12058078
TI  - The bending rigidity of mitotic chromosomes.
AB  - The bending rigidities of mitotic chromosomes isolated from cultured N.
      viridescens (newt) and Xenopus epithelial cells were measured by observing their
      spontaneous thermal bending fluctuations. When combined with simultaneous
      measurement of stretching elasticity, these measurements constrain models for
      higher order mitotic chromosome structure. We measured bending rigidities of B
      approximately 10(-22) N. m(2) for newt and approximately 10(-23) N. m(2) for
      Xenopus chromosomes extracted from cells. A similar bending rigidity was measured
      for newt chromosomes in vivo by observing bending fluctuations in metaphase
      arrested cells. Following each bending rigidity measurement, a stretching
      (Young's) modulus of the same chromosome was measured in the range of 10(2) to
      10(3) Pa for newt and Xenopus chromosomes. For each chromosome, these values of B
      and Y are consistent with those expected for a simple elastic rod, B
      approximately YR(4), where R is the chromosome cross-section radius. Our
      measurements rule out the possibility that chromosome stretching and bending
      elasticity are principally due to a stiff central core region and are instead
      indicative of an internal structure, which is essentially homogeneous in its
      connectivity across the chromosome cross-section.

PMID- 12058077
TI  - A polymer model for large-scale chromatin organization in lower eukaryotes.
AB  - A quantitative model of large-scale chromatin organization was applied to nuclei
      of fission yeast Schizosaccharomyces pombe (meiotic prophase and G2 phase),
      budding yeast Saccharomyces cerevisiae (young and senescent cells), Drosophila
      (embryonic cycles 10 and 14, and polytene tissues) and Caenorhabditis elegans (G1
      phase). The model is based on the coil-like behavior of chromosomal fibers and
      the tight packing of discrete chromatin domains in a nucleus. Intrachromosomal
      domains are formed by chromatin anchoring to nuclear structures (e.g., the
      nuclear envelope). The observed sizes for confinement of chromatin diffusional
      motion are similar to the estimated sizes of corresponding domains. The model
      correctly predicts chromosome configurations (linear, Rabl, loop) and chromosome
      associations (homologous pairing, centromere and telomere clusters) on the basis
      of the geometrical constraints imposed by nuclear size and shape. Agreement
      between the model predictions and literature observations supports the notion
      that the average linear density of the 30-nm chromatin fiber is approximately 4
      nucleosomes per 10 nm contour length.

PMID- 12058080
TI  - MRI vs EMG: which has the upper hand in carpal tunnel syndrome?

PMID- 12058079
TI  - Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that
      is a member of the PIF1 subfamily of DNA helicases.
AB  - The Saccharomyces cerevisiae Pif1p DNA helicase is the prototype member of a
      helicase subfamily conserved from yeast to humans. S. cerevisiae has two PIF1
      like genes, PIF1 itself and RRM3, that have roles in maintenance of telomeric,
      ribosomal, and mitochondrial DNA. Here we describe the isolation and
      characterization of pfh1+, a Schizosaccharomyces pombe gene that encodes a Pif1
      like protein. Pfh1p was the only S. pombe protein with high identity to
      Saccharomyces Pif1p. Unlike the two S. cerevisiae Pif1 subfamily proteins, the S.
      pombe Pfh1p was essential. Like Saccharomyces Pif1p, a truncated form of the S.
      pombe protein had 5' to 3' DNA helicase activity. Point mutations in an invariant
      lysine residue in the ATP binding pocket of Pfh1p had the same phenotype as
      deleting pfh1+, demonstrating that the ATPase/helicase activity of Pfh1p was
      essential. Although mutant spores depleted for Pfh1p proceeded through S phase,
      they arrested with a terminal cellular phenotype consistent with a postinitiation
      defect in DNA replication. Telomeric DNA was modestly shortened in the absence of
      Pfh1p. However, genetic analysis demonstrated that maintenance of telomeric DNA
      was not the sole essential function of S. pombe Pfh1p.

PMID- 12058081
TI  - Picking away at frontotemporal dementia.

PMID- 12058082
TI  - Cerebral amyloid angiopathy and dementia: two amyloids are worse than one.

PMID- 12058083
TI  - Practice parameter: Electrodiagnostic studies in carpal tunnel syndrome. Report
      of the American Association of Electrodiagnostic Medicine, American Academy of
      Neurology, and the American Academy of Physical Medicine and Rehabilitation.

PMID- 12058084
TI  - Mimic syndromes in sporadic cases of progressive spinal muscular atrophy.
AB  - Described are patients initially diagnosed with progressive spinal muscular
      atrophy (PSMA), in whom further evaluation established another diagnosis. The
      authors prospectively investigated incident and prevalent cases of PSMA.
      Seventeen of 89 patients, after initial registration, were later excluded because
      reassessment revealed a diagnosis other than PSMA. In 11 of the 17 patients with
      a revised diagnosis, a potential treatment was available: multifocal motor
      neuropathy (7), chronic inflammatory demyelinating polyneuropathy (2),
      inflammatory myopathy (1), and MG (1). Other misdiagnoses included myopathy,
      syringomyelia, ALS, idiopathic chronic axonal polyneuropathy, and idiopathic
      brachial plexus neuropathy. One patient with a possible herniated lumbar disk
      recovered spontaneously.

PMID- 12058085
TI  - MR nerve imaging in a prospective cohort of patients with suspected carpal tunnel
      syndrome.
AB  - OBJECTIVES: To evaluate the reliability and diagnostic accuracy of high
      resolution MRI of the median nerve in a prospectively assembled cohort of
      subjects with clinically suspected carpal tunnel syndrome (CTS). METHODS: The
      authors prospectively identified 120 subjects with clinically suspected CTS from
      five Seattle-area clinics. All subjects completed a hand-pain diagram and
      underwent a standardized nerve conduction study (NCS). The reference standard for
      determining CTS status was a classic or probable hand pain diagram and NCS with a
      difference >0.3 ms between the 8-cm median and ulnar peak latencies. Readers
      graded multiple imaging parameters of the MRI on four-point scales. The authors
      also performed quantitative measurements of both the median nerve and carpal
      tunnel cross-sectional areas. NCS and MRI were interpreted without knowledge of
      the other study or the hand pain diagram. RESULTS: Intrareader reliability was
      substantial to near perfect (kappa = 0.76 to 0.88). Interreader agreement was
      lower but still substantial (kappa = 0.60 to 0.67). Sensitivity of MRI was
      greatest for the overall impression of the images (96%) followed by increased
      median nerve signal (91%); however, specificities were low (33 to 38%). The
      length of abnormal signal on T2-weighted images was significantly correlated with
      nerve conduction latency, and median nerve area was larger at the distal
      radioulnar joint (15.8 vs 11.8 mm(2)) in patients with CTS. A logistic regression
      model combining these two MR variables had a receiver operating characteristic
      area under the curve of 0.85. CONCLUSIONS: The reliability of MRI is high but the
      diagnostic accuracy is only moderate compared with a research-definition
      reference standard.

PMID- 12058086
TI  - Comparison of motor conduction techniques in the diagnosis of carpal tunnel
      syndrome.
AB  - OBJECTIVE: To compare the sensitivities of motor wrist-to-palm (W-P) conduction
      velocity and two median-ulnar motor latency differences with that of sensory W-P
      conduction velocity in the diagnosis of carpal tunnel syndrome (CTS). METHODS:
      This study included 116 consecutive patients with CTS (160 hands) referred for
      evaluation and 100 volunteers who served as controls. Median motor and sensory
      nerve responses with wrist and palm stimulation allowed for the determination of
      motor and sensory W-P CV (W-P MCV and SCV). Two motor distal latency (MDL)
      differences between the median-thenar and ulnar-hypothenar (M-U) muscles and
      between the median-second lumbrical and ulnar-interossei muscles (2L-INT) were
      measured and calculated. The mean values of controls plus or minus 2.5 SD served
      as the normal limits. RESULTS: Among the 160 hands with suspected CTS, 11 (6.88%)
      had normal electrodiagnostic studies and 149 (93.1%) had at least one abnormal
      electrodiagnostic study. Among the 149 hands with an abnormality, 139 (86.88%)
      had abnormal W-P MCV and 129 (80.63%) had abnormal W-P SCV. The sensitivity for
      2L-INT was 77.5%, and it was 70% for M-U, 68.75% for median MDL, and 73.75% for
      sensory distal latency. Combining W-P MCV and W-P SCV allowed for the detection
      of abnormalities in 147 hands (91.88%) and yielded a markedly improved diagnostic
      rate compared with W-P SCV alone. CONCLUSION: Motor W-P conduction study is more
      valuable and no more difficult than sensory W-P conduction study for the
      diagnosis of CTS. In patients with suspected CTS in whom the results of
      conventional nerve conduction studies are normal, studying both motor and sensory
      W-P conduction increases the diagnostic yield.

PMID- 12058088
TI  - The prevalence of frontotemporal dementia.
AB  - OBJECTIVE: To estimate the prevalence of frontotemporal dementia (FTD) and other
      degenerative early-onset dementias in a geographically defined population.
      BACKGROUND: Early-onset dementia (at age <65 years) results in high psychiatric
      morbidity and caregiver burden. Prevalence figures are available for early-onset
      AD but not for FTD, a dementia that is almost invariably of early onset. METHODS:
      Case ascertainment was by review of case records of three specialist clinic
      databases and inpatient admissions at a university hospital in Cambridge, United
      Kingdom, for patients with dementia who were <65 years of age, living in
      Cambridge City or East or South Cambridgeshire (population 326,019) on May 30,
      2000. All the relevant health services in the area were also contacted for
      potential cases. Diagnosis of various dementias was based on published criteria.
      All patients with potential FTD were examined by the study investigators and
      underwent structural neuroimaging. The 1998 population estimates for the area
      were used to calculate age and sex prevalence with confidence intervals for AD,
      FTD, and other causes of dementia. RESULTS: A total of 108 patients (66 men and
      42 women) with dementia with onset before they were 65 years of age were
      identified, of whom 60 were <65 years on the census date, giving an overall
      prevalence of 81 (95% CI, 62.8 to 104.5) per 100,000 in the 45- to 64-year age
      group. The prevalences of early-onset FTD and AD were the same: 15 per 100,000
      (8.4 to 27.0) in the 45- to 64-year-old population. The mean age at onset of FTD
      was 52.8 years and there was a striking male preponderance (14:3). It is possible
      case ascertainment methods resulted in a relative underrepresentation of some
      forms of dementia. CONCLUSIONS: Frontotemporal dementia is a more common cause of
      early-onset dementia than previously recognized and appears to be more common in
      men.

PMID- 12058087
TI  - Utility of clinical criteria in differentiating frontotemporal lobar degeneration
      (FTLD) from AD.
AB  - OBJECTIVE: To assess the ability of the current diagnostic criteria for
      frontotemporal lobar degeneration (FTLD) to differentiate FTLD from AD. METHODS:
      Thirty cases with autopsy-proven FTLD and 30 cases of AD, matched for Mini-Mental
      State Examination score, were identified from the clinical databases of three
      dementia subspecialty centers, and their charts were reviewed for the presence of
      clinical features described in the current criteria for FTLD. The proportion of
      patients with each clinical feature at the first clinical presentation was
      compared across groups. RESULTS: A significantly larger proportion of patients
      with FTLD showed behavioral abnormalities, particularly social and personal
      conduct disorders and emotional blunting, than patients with AD. Few differences
      in language features were seen between the groups, and many of the language
      features detailed in the criteria were found in only a small proportion of
      patients. In both groups, many patients showed neuropsychological abnormalities,
      except for perceptual difficulties, which were present in many patients with AD
      but only in a few patients with FTLD. Extrapyramidal motor symptoms were more
      likely to be present in FTLD. Logistic regression revealed that five features
      social conduct disorders, hyperorality, akinesia, absence of amnesia, and the
      absence of a perceptual disorder-correctly classified 93% of patients with FTLD
      and 97% of patients with AD. CONCLUSION: A combination of behavioral,
      neuropsychological, and physical findings is most useful in distinguishing FTLD
      from AD. Future studies should be directed at establishing more objective methods
      of identifying these clinical features.

PMID- 12058089
TI  - Tau and Abeta42 protein in CSF of patients with frontotemporal degeneration.
AB  - BACKGROUND: CSF concentrations of tau and beta-amyloid protein-42 (Abeta42) have
      been extensively studied in AD. Few data are available concerning CSF levels of
      both proteins in patients with frontotemporal degeneration (FTD). METHODS: The
      authors investigated CSF tau and Abeta42 concentrations in 34 patients with FTD,
      74 patients with AD, and 40 cognitively healthy control subjects. CSF levels of
      tau and Abeta42 were measured by ELISA. With use of receiver operating
      characteristic-derived cutoff points and linear discrimination lines, the
      diagnostic sensitivity and specificity of both markers were determined. RESULTS:
      CSF tau concentrations were significantly higher in FTD than in control subjects
      but were significantly lower than in AD. CSF Abeta42 levels were significantly
      lower in FTD than in control subjects but were significantly higher than in AD.
      In subjects with FTD, neither tau nor Abeta42 levels correlated with the severity
      of dementia. The best discrimination between the diagnostic groups was obtained
      by simultaneous measurement of tau and Abeta42, yielding a sensitivity of 90% at
      a specificity of 77% (FTD vs controls) and a sensitivity of 85% at a specificity
      of 85% (FTD vs AD). CONCLUSIONS: In FTD, CSF levels of tau are elevated and
      Abeta42 levels are decreased. With use of these markers, subjects with FTD can be
      distinguished from control subjects and from patients with AD with reasonable
      accuracy.

PMID- 12058090
TI  - Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study.
AB  - OBJECTIVE: To investigate the relationship between cerebral amyloid angiopathy
      (CAA), dementia, and cognitive function in an autopsy sample of 211 Japanese
      American men from the population-based Honolulu-Asia Aging Study. METHODS:
      Starting in 1991, participants were assessed with the Cognitive Abilities
      Screening Instrument (CASI) and diagnosed with dementia (including subtype) based
      on published criteria. At autopsy, neuropathologists blinded to clinical data
      examined brains for neurofibrillary tangles (NFT), neuritic plaques (NP), and a
      number of vascular pathologies, including CAA. CAA was detected by immunostaining
      for betaA4 amyloid in parenchymal vessels in the neocortex and semiquantitatively
      rated. Linear regression models were used to examine the association of CASI
      score, dementia subtype, and CAA controlling for age at death, time between CASI
      administration and death, education, NP and NFT counts, infarcts, hemorrhage, and
      APOE genotype. RESULTS: A total of 44.1% of subjects had CAA in at least one
      neocortical area. The presence of CAA was associated with higher mean NFT and NP
      counts and having at least one APOE-epsilon4 allele. The interaction between CAA
      and AD on the adjusted mean CASI score was significant; compared with nondemented
      men without CAA, the CASI score was 16.6% lower in men with AD and no CAA and
      45.9% lower in men with AD plus CAA. CONCLUSIONS: CAA may contribute to the
      clinical presentation of dementia by interacting with other neuronal pathologies,
      leading to more severe cognitive impairment in men with both CAA and AD compared
      with men with only AD or CAA.

PMID- 12058091
TI  - Effects of subcortical ischemic vascular dementia and AD on entorhinal cortex and
      hippocampus.
AB  - OBJECTIVE: To determine the effects of subcortical ischemic vascular dementia
      (SIVD) and AD on entorhinal cortex (ERC) and hippocampus. METHODS: Thirty-eight
      cognitively normal subjects, 18 patients with SIVD, and 22 patients with AD were
      included. Volumes of ERC and hippocampus were manually measured based on MRI.
      Global cerebral changes of cortical gray matter, subcortical gray matter, white
      matter, sulcal CSF, ventricular CSF (vCSF), and white matter signal
      hyperintensities (WMSH) were assessed. RESULTS: Patients with SIVD had 21.7% (p <
      0.01) smaller ERC and 18.2% (p < 0.01) smaller hippocampi than cognitively normal
      subjects and 24.4% (p < 0.01) larger ERC and 11.1% (p < 0.05) larger hippocampi
      than patients with AD. In addition, patients with SIVD had less cortical gray
      matter and white matter and more vCSF and WMSH (all p < 0.01) than cognitively
      normal subjects and more vCSF and WMSH (p < 0.01) than patients with AD. The
      volumes of ERC and hippocampus were positively correlated to similar extents (p <
      0.01) in SIVD and AD. Cortical gray matter loss was positively correlated (p <
      0.01) with hippocampal atrophy, but not with ERC atrophy, in SIVD and AD.
      Hippocampal volume alone could classify 82% of patients with SIVD from
      cognitively normal subjects and 63% of patients with SIVD from subjects with AD.
      Adding global cerebral changes to hippocampus substantially improved the
      classification to 96% between patients with SIVD and cognitively normal subjects
      and 83% between subjects with SIVD and those with AD, whereas adding ERC change
      to hippocampus did not significantly improve the discrimination. CONCLUSIONS: The
      entorhinal cortex and hippocampus are less affected by subcortical ischemic
      vascular dementia than by AD.

PMID- 12058092
TI  - Clinical and pathologic characteristics of nontyphoidal salmonella
      encephalopathy.
AB  - OBJECTIVE: To investigate the clinical and pathologic characteristics of primary
      encephalopathy caused by nontyphoidal salmonellosis (NTS). METHODS: Case records
      of six Japanese hospitals from 1994 to 1999 were reviewed. Eight cases of primary
      NTS encephalopathy were identified based on strictly defined criteria: 1)
      encephalopathic feature defined as altered state of consciousness, altered
      cognition or personality, or seizures; 2) detection of nontyphoidal Salmonella
      species in stool; 3) absence of other viral or bacterial infection associated
      with CNS abnormalities; and 4) absence of alternative explanation by underlying
      neurologic or systemic disease. Three patients died, three had severe sequelae,
      and two recovered completely. The authors analyzed their clinical course,
      neurologic symptoms, and histopathologic findings. RESULTS: NTS encephalopathy
      was clinically characterized by diffuse and rapidly progressive brain dysfunction
      and circulatory failure that developed following enteritis. There was no evidence
      of severe dehydration or sepsis, and encephalopathy was rarely accompanied by
      abnormal laboratory data, except elevated CSF opening pressure, brain edema on
      CT, and slow waves on EEG. Pathologic findings included minimal ischemic damage
      and mild edema in the brain, microvesicular fatty change of the liver, severe
      enterocolitis but no evidence of dehydration, and no fatal organ damage including
      microvasculature and endothelial cells. CONCLUSION: Noninfectious encephalopathy
      associated with nontyphoidal salmonella infection is a distinctive clinical
      entity that can be differentiated from Reye's syndrome and Ekiri.

PMID- 12058093
TI  - Focal and global cortical hypometabolism in patients with newly diagnosed
      infantile spasms.
AB  - OBJECTIVE: To evaluate the occurrence and prognostic importance of focal defects
      in cerebral cortical glucose metabolism in infants with newly diagnosed
      symptomatic and cryptogenic infantile spasms. PATIENTS AND METHODS: Ten children
      with symptomatic and seven with cryptogenic infantile spasms underwent MRI, video
      EEG, and PET using fluorodeoxyglucose as a tracer within 2 weeks of diagnosis.
      PET was repeated at 1 year of age in 12 patients. RESULTS: Cortical hypometabolic
      foci were found in 13 children (77%) with newly diagnosed spasms (six cryptogenic
      and seven symptomatic). The hypometabolic foci disappeared in seven of nine
      reexamined at age 1. The occipital foci disappeared in all (n = 6). Focal
      findings on PET correlated well with focal findings on video-EEG. There was no
      difference in quantitative cortical or subcortical glucose metabolic rate at the
      onset of infantile spasms between children with cryptogenic and symptomatic
      etiology of spasms. The glucose metabolic rate at the onset of spasms or focal
      lesions in glucose metabolism did not have prognostic value for seizure outcome.
      CONCLUSIONS: Infantile spasms are often associated with transient cortical,
      especially occipital, hypometabolic foci that are not necessarily associated with
      structural lesions and do not indicate a poor prognosis.

PMID- 12058094
TI  - A randomized trial of divalproex sodium extended-release tablets in migraine
      prophylaxis.
AB  - OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex
      sodium compared with placebo in prophylactic monotherapy treatment of migraine
      headache. METHODS: This was a double-blind, randomized, placebo-controlled,
      parallel-group study. Subjects with more than two migraine headache attacks
      during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to
      receive either extended-release divalproex sodium or matching placebo once daily
      for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and
      the dose was then increased to 1,000 mg once daily with an option, if intolerance
      occurred, to permanently decrease the dose to 500 mg during the second week.
      Reduction from baseline in 4-week migraine headache rate was the primary efficacy
      variable. Migraine headaches separated by a < 24-hour headache-free interval were
      counted as single migraines in calculating migraine headache rates. Tolerance and
      safety were also evaluated. RESULTS: The mean reductions in 4-week migraine
      headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release
      divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo
      group (p = 0.006); reductions with extended-release divalproex sodium were
      significantly greater than with placebo in all three 4-week segments of the
      treatment period. No significant differences were detected between treatment
      groups in either the overall incidence or in the incidence of any specific
      treatment-emergent adverse event; 8% of subjects treated with extended-release
      divalproex sodium and 9% of those treated with placebo discontinued for adverse
      events. CONCLUSION: Extended-release divalproex sodium is an efficacious, well
      tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.

PMID- 12058095
TI  - Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical
      trial.
AB  - BACKGROUND: Certain nonsteroidal anti-inflammatory drugs are effective in the
      acute treatment of migraine attacks. The authors report a double-blind, placebo
      controlled, randomized cross-over trial of a dual-release formulation of oral
      ketoprofen in the acute treatment of migraine attacks. METHODS: The authors
      compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of
      placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to
      four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized
      patients) with migraine with or without aura. The principal efficacy outcome was
      headache relief (reduction in headache severity from severe or moderate to mild
      or absent at 2 hours). RESULTS: Results are based on 838 attacks with a severe or
      moderate headache that were evaluable at 2 hours. Relief was reported for 62.6%
      of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and
      66.8% with zolmitriptan. The difference between the three active treatments and
      placebo (27.8% relief) was highly significant, both tests of ketoprofen vs
      placebo being globally controlled at a 5% level for the type I error (primary
      analysis). Headaches at 2 hours disappeared more frequently for the active
      treatments than for placebo. The authors also demonstrated efficacy on most other
      secondary outcomes. The tolerance of ketoprofen was good (similar to that of
      placebo). CONCLUSIONS: Oral ketoprofen (75 mg or 150 mg) in a dual-release
      formulation is an effective and well-tolerated drug in the acute treatment of
      migraine attacks.

PMID- 12058096
TI  - Effects of subthalamic nucleus stimulation on motor cortex excitability in
      Parkinson's disease.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS) studies have found
      abnormalities in several excitatory and inhibitory circuits in the motor cortex
      in PD. These include motor evoked potential (MEP) recruitment curve, silent
      period duration (SP), short-interval intracortical inhibition (SICI),
      intracortical facilitation (ICF), and long-interval intracortical inhibition
      (LICI). METHODS: The authors studied the effects of subthalamic nucleus (STN)
      deep brain stimulation (DBS) on these circuits in 12 patients with PD treated
      with STN DBS. Data from nine patients who completed the study were analyzed.
      Patients remained on their usual medications. The stimulators were set at the
      optimal parameters (ON), half the optimal amplitude (HALF), and switched off
      (OFF) in random order. RESULTS: The Unified PD Rating Scale motor scores were
      significantly lower in the ON compared to the HALF and OFF conditions. Resting
      SICI, studied with paired-pulse TMS at interstimulus interval of 2 ms, was
      reduced in the OFF and HALF conditions compared to normal subjects. STN
      stimulation restored SICI to normal levels. STN stimulation had no effect on
      motor threshold, MEP recruitment curve, SP, active SICI, ICF, and LICI.
      CONCLUSIONS: Although restoration of short-interval intracortical inhibition by
      STN stimulation is similar to the effects of dopaminergic drugs, it has no effect
      on silent period duration and long-interval intracortical inhibition, which are
      also influenced by dopaminergic drugs. A previous study found that internal
      globus pallidus (GPi) stimulation reduced SP but did not change SICI. Thus, GPi
      and STN stimulation may affect different circuits in the motor cortex.

PMID- 12058097
TI  - HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration.
AB  - HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and
      pallidal degeneration) is a rare syndrome with many clinical similarities to
      pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden
      Spatz syndrome). Despite these common features, lipoprotein abnormalities have
      not been reported in PKAN. After the recent discovery of the genetic defect in
      PKAN, we report a homozygous nonsense mutation in exon 5 of the PANK2 gene that
      creates a stop codon at amino acid 371 (R371X) in the original HARP patient. This
      finding establishes that HARP is part of the PKAN disease spectrum.

PMID- 12058099
TI  - Numular headache: a coin-shaped cephalgia.
AB  - Numular headache is a chronic, mild to moderate, pressurelike pain in a
      circumscribed cranial area of approximately 2 to 6 cm in diameter. Pain usually
      is limited to the parietal region, although it may appear in any cranial site. It
      is a benign process of usually unknown origin.

PMID- 12058098
TI  - Peroneal nerve palsy caused by thrombosis of crural veins.
AB  - Acute palsies of the peroneal nerve may have a variety of causes. In many
      patients, the cause remains undetermined. The authors report a patient with a
      thrombosis of a crural vein causing an acute peroneal nerve palsy. If the
      clinical history of patients with an acute peroneal nerve lesion is suggestive of
      venous thrombosis an appropriate diagnostic workup should be considered.

PMID- 12058100
TI  - A crossover, add-on trial of talampanel in patients with refractory partial
      seizures.
AB  - The authors report a double-blind, placebo-controlled, crossover study of
      talampanel in 49 patients with refractory partial seizures. Three doses of
      talampanel were investigated based on differences in patients' concomitant
      antiepileptic drug usage. Talampanel showed efficacy in reducing seizure
      frequency (p = 0.001) with a median seizure reduction of 21%. Eighty percent of
      patients had fewer seizures on talampanel than on placebo. Dizziness (52%) and
      ataxia (26%) were the only significant adverse events.

PMID- 12058101
TI  - Bilateral isolated hippocampal malformation in temporal lobe epilepsy.
AB  - Hippocampal malformations in patients with epilepsy usually are reported in the
      context of widespread cortical malformations. Isolated hippocampal malformations
      are more rarely identified in MRI studies with little documentation of their
      pathologic appearance. Postmortem examination revealed abnormal position and
      complex convolutional malformations isolated to the hippocampal formation in an
      adult with temporal lobe epilepsy in whom MRI demonstrated bilateral hippocampal
      abnormalities.

PMID- 12058102
TI  - Brainstem involvement in Unverricht-Lundborg disease (EPM1): An MRI and (1)H MRS
      study.
AB  - MRI of the brain and proton MRS ((1)H MRS) of the pons and dentate were obtained
      in 10 patients with genetically confirmed Unverricht-Lundborg disease (EPM1) and
      20 control subjects. Patients with EPM1 showed (p < or = 0.01) loss of bulk of
      the basis pontis, medulla, and cerebellar hemispheres. Cerebral atrophy was
      present in six patients. The N-acetylaspartate/creatine and choline/creatine
      ratios were reduced in the pons but not in the dentate (p < or = 0.005).
      Brainstem involvement could play a role in pathophysiology of EPM1.

PMID- 12058103
TI  - Thalamic venous infarction as a cause of subacute dementia.
AB  - The clinical picture of deep cerebral vein thromboses (DCVT) usually is acute,
      combining vigilance disorders, headaches, and focal neurologic deficit. The
      authors describe a patient who presented with isolated subacute dementia as the
      sole manifestation of DCVT. In the setting of subacute cognitive deficit, the
      diagnosis of DCVT must be considered when neuroimaging shows bilateral thalamic
      changes. Enhanced venous MR angiography is the noninvasive method of choice to
      ascertain the diagnosis.

PMID- 12058104
TI  - The contribution of an avoidance response to contralateral neglect.
AB  - Displacement of line bisection to the right of midline in a patient with a right
      hemisphere lesion has been attributed to either contralesional attentional or
      intentional hemispatial neglect. However, it has been suggested that patients
      with hemispheric lesions might also have an avoidance response, and the
      ipsilesional eye and hand deviation attributed to neglect might, at least in
      part, be related to this response. The authors report a patient with a net
      contralateral neglect produced by the combination of intention and avoidance
      factors.

PMID- 12058105
TI  - Massive air embolism with left ventricular assist device.

PMID- 12058106
TI  - Stroke induced by gamma knife pallidotomy: autopsy result.

PMID- 12058107
TI  - Isolated thermoanesthesia associated with a midlateral medullary infarction.

PMID- 12058108
TI  - Wernicke's encephalopathy in a woman on slimming diet.

PMID- 12058109
TI  - SUNCT syndrome in two patients with prolactinomas and bromocriptine-induced
      attacks.

PMID- 12058110
TI  - Intracranial hypotension with air bubble on head CT.

PMID- 12058111
TI  - The Seven Deadly Sins revised and edited for physicians of the 21st century.

PMID- 12058112
TI  - Older people with impaired mobility have specific loci of periventricular
      abnormality on MRI.

PMID- 12058113
TI  - Randomized controlled trial of zonisamide for the treatment of partial-onset
      seizures.

PMID- 12058114
TI  - Bilateral human fetal striatal transplantation in Huntington's disease.

PMID- 12058115
TI  - Chronic ischemic monomelic neuropathy from critical limb ischemia.

PMID- 12058116
TI  - Cognitive deficits in patients with essential tremor.

PMID- 12058117
TI  - Localization of Claude's syndrome.

PMID- 12058118
TI  - Relationship between severity of MR perfusion deficit and DWI lesion evolution.

PMID- 12058120
TI  - [Harvey Cushing (1869-1939)].

PMID- 12058121
TI  - [The history of Cushing's disease].

PMID- 12058122
TI  - [Pathology and pathogenesis of pituitary corticotroph adenoma].
AB  - Corticotroph adenoma is a benign tumor composed of adenohypophyseal cells;
      carcinoma with metastasis and ectopic adenoma have also been reported. In our
      pathological series, the frequency of this type of adenoma is 13% (250/1863
      tumors removed between 1970 and 2001). Usually, corticotroph adenomas synthesize
      peptides derived from POMC maturation: ACTH, ss-endorphine, and ssLPH. In the
      great majority of cases, ACTH induces hypercorticism with clinical and biological
      signs of Cushing's disease. However, some tumors the pathologist identifies as
      corticotroph adenomas are not associated with clinical signs of hypercorticism
      (20% of the corticotroph adenomas in our series). Corticotroph adenoma is a
      basophilic or chromophobe tumor composed of cells which remain regulated by
      cortisol. This may explain the small size of this type of adenoma in 80% of the
      cases. In contrast, "silent" adenomas or macroadenonas which synthesize high
      weight POMC are aggressive invasive tumors. Neurosurgery is indicated for the
      treatment of corticotroph adenoma. Recurrence is explained by incomplete removeal
      of the tumor. Peroperative studies may be necessary to find microadenomas. In
      some cases, the whole pituitary must be removed and cut in serial sections to
      find a tumor measuring<2 mm. In our opinion, the existence of corticotroph
      hyperplasia inducing Cushing's disease remains to be proven (we have never
      observed one). The pituitary origin of the tumor is based on its monoclonality.
      The general mechanism of tumorigenesis is known, but the specific factors
      involved and markers of aggressiveness remain to be discovered.

PMID- 12058123
TI  - [Differential diagnosis and medical treatment in Cushing's disease].
AB  - Cushing's disease remains a difficult diagnosis in spite of new technical
      procedures such as pituitary MRI, selective bilateral petrosal or cavernous
      sampling, (111)In pentreotide scan and 18 Flurodeoxyglucose pituitary PET scan.
      In this article, we review biological diagnostic procedures of Cushing's disease
      and corticotroph adenomas. According to our experience and the literature, we
      summarize the approach in medical treatment of Cushing's disease.

PMID- 12058125
TI  - [Technical aspects and surgical strategy for removal of corticotroph pituitary
      adenoma].
AB  - The development of transsphenoidal microsurgery and the refinement of
      endocrinological and radiological diagnostic procedures have afforded therapeutic
      options appropriate for each individual case in patients with pituitary-dependent
      hypercortisolism. Compared with other secreting pituitary tumors, the
      corticotroph adenoma seems to be the most biologically active tumor. Clinical
      evidence of hypercortisolism mainly occurs at an early stage of tumor growth when
      the tumor is very small, below the detection threshold of modern imaging
      techniques. While the treatment of large tumors remains difficult due to the non
      discrete boundary lines of the tumor and extension or invasion, surgical removal
      of very tiny tumors requires reliable preoperative or peroperative identification
      in order to achieve total tumor resection for clinical remission and pituitary
      preservation to prevent hypopituitarism. We reviewed all the current surgical
      techniques or clever surgical procedures used to achieve both goals with the
      lowest complication rate. We report here the state-of-the-art of surgical
      management of corticotroph pituitary adenoma focusing on preoperative
      radiological and biological data required for performing guided intrasellar
      surgical exploration and reliable tumor identification. Different technical
      aspects of the nasosphenoidal approaches are reported as well as the modified
      transdiaphragmatic or transtubercular transcisternal approaches to tumors in a
      suprasellar localization or lying along the pituitary stalk. The advantages of
      minimally invasive surgical techniques such as intrasellar endoscopic surgery are
      discussed. Adapted surgical techniques for second transnasal surgery indicated
      for recurrent tumors are described. Guidelines are given for peroperative tumor
      identification with macroscopic assessment or histological control with frozen
      section biopsies. Different techniques for tumor removal are discussed from
      selective microadenomectomy to enlarged pituitary resection and total
      hypophysectomy. Methods for preoperative guidance of total tumor removal are
      proposed including histological or biological assessment of normal adjacent
      pituitary tissue. the strategy of surgical intrasellar exploration and tumor
      resection is outlined using a set of algorithms. The first is devoted to positive
      preoperative documentation of the tumor. The second is proposed for the surgical
      scenario where there is no preoperative MRI evidence of the tumor. Special
      strategies are discussed for ectopic adenoma or multiple tumors. Revision
      surgical management after surgical failure or tumor recurrence is described.
      Special guidelines for surgical treatment of large clinically silent corticotroph
      macroadenomas are given with emphasis on the high risk of recurrence in
      comparison with other silent pituitary tumors such as gonadotroph or
      immunonegative adenomas.

PMID- 12058124
TI  - [Pituitary gland imaging in Cushing's disease].
AB  - Specific MR techniques are required for optimal detection of adenocorticotropic
      hormone secreting adenomas responsible for Cushing's disease. Adequate MR
      sequences, high resolution coronal T1 and T2 - weighted images, dynamic MR
      imaging, post-gadolinium delayed images, dose of gadolinium adjusted for each
      sequence can routinely demonstrate pituitary adenomas less than 3 mm in Cushing's
      disease.

PMID- 12058126
TI  - [Corticotroph microadenomas of the pituitary stalk. Diagnostic and therapeutic
      difficulties].
AB  - Thirteen percent of the pituitary adenomas in our series have been corticotroph
      adenomas. Most have been microadenomas located in the adenohypophysis, more often
      laterally than posteromedially. In a few rare cases, the corticotroph cells of
      the pars tuberalis gave rise to an adenoma. Only 16 cases of pituitary stalk
      adenomas have been published to date. We report here three new cases among a
      series of 150 patients who underwent surgery for corticotroph adenomas (2%
      incidence as in the literature). There was no difference in the clinical or
      biological presentation of intrasellar and pituitary stalk adenomas. This
      location must be systematically searched on the MRI, but a negative exploration
      cannot excluded the diagnosis of pituitary stalk adenoma like in intrasellar
      ones. Two anatomical entities seems to be separated. Some stalk adenomas
      developed preferentially in the supradiaphragmatic space (one in our series) and
      are accessible for selective resection. Others develop within the pituitary stalk
      itself and sometimes in the pars distalis (two patients in our series) which
      requires section of the pituitary stalk with hypophysectomy if the lower limit is
      not clearly seen during surgery. The subfrontal or pterional access is the
      approach of choice for suprasellar tumors. These approaches remain controversial
      for pituitary stalk adenomas because of the poor visibility of the pituitary
      stalk and the floor of the third ventricle. The transnasosphenoidal approach with
      extension to the sphenoidal planum and opening of the optochiasmatic cisterna
      appears to be the best alternative for surgical removal of these adenomas.

PMID- 12058127
TI  - [Role of perioperative biological tests during the performance and follow-up of
      corticotroph adenoma exeresis].
AB  - ACTH assay in cavernous sinus samples during resection of pituitary
      adrenocorticotroph adenomas is a simple and safe technique providing an
      intraoperative assessment of adrenocorticotroph hormone gradients. Bilateral
      puncture of the cavernous sinus can be achieved vial the standard transsphenoidal
      approach to the sella turcica. ACTH is determined with IRMA at 37;C with an
      incubation time of less than one hour. Among 71 cases in our experience, the ACTH
      gradient accurately predicted the position of the adenoma in 93% of the cases.
      This rate is higher than the 61% accuracy reported for inferior petrosal sinus
      sampling. The technique reported is more precise than MRI which correctly
      identifies adenomas in only 50% of the cases. The remaining cases are either
      false positives or false negatives. We report an 82% cure rate either via direct
      resection of the microadenoma or via partial hypophysectomy guided by the ACTH
      gradient. In our series, 20 cases of Cushing's disease had a normal MRI and no
      surgically identifiable adenoma. In 10 of these cases however, cure was achieved
      by performing ACTH gradient guided partial hypophysectomy. This method produces
      no morbidity and is most helpful for the neurosurgeon allowing confirmation of
      the position of an MRI-visible adenoma or an adenoma identified intraoperatively.
      It does not however replace neurosurgical experience which remains the most
      important predictive factor for outcome in surgical treatment of Cushing's
      disease.

PMID- 12058128
TI  - [Cushing's disease and corticotroph adenoma: anterior pituitary function before
      and after trans-sphenoidal microsurgery].
AB  - BACKGROUND AND PURPOSE: Cushing's disease is characterized by an overproduction
      of ACTH inducing an hypersecretion of corticosteroids. We assessed the non
      corticotrophic pituitary functions before and after microsurgical resection of
      the corticotrophic adenoma. METHODS: We reviewed retrospectively a series of 98
      patients (19 males, 79 females) undergoing transsphenoidal surgery between 1974
      and 2001. Prolactin levels, somatrotrophic, gonadotrophic and thyroidotrophic
      functions were assessed and compared before and after resection of the adenoma.
      RESULTS: Before surgery, we observed an elevation of prolactin and a reduction of
      the GH, TSH, LH and FSH levels. These modifications were not linked to the volume
      of the adenoma but depended on the systemic effect of the hypercorticism or on
      local paracrine mechanisms. Selective adenomectomy usually restored altered
      corticotrophic and also, unlike (partial or total) hypophysectomy, the non
      corticotrophic functions. CONCLUSIONS: Non-corticotrophic functions are often
      altered in Cushing's disease but can be restored after selective adenomectomy.

PMID- 12058130
TI  - [Indications for total hypophysectomy in Cushing's disease].
AB  - OBJECTIVE: Transsphenoidal selective adenomectomy is the treatment of choice for
      Cushing's disease. In some patients, magnetic resonance imaging (MRI) fails to
      detect small pituitary ACTH-secreting adenomas. Total hypophysectomy can be
      performed when MRI appears normal. The aim of this paper is to study results and
      complications after total hypophysectomy for Cushing's disease. METHODS: Between
      July 1988 and May 1999, 49 patients underwent transsphenoidal surgery for
      Cushing's disease at our institution. The criteria for inclusion in this study
      were clinical and biochemical studies strongly suggestive of Cushing's disease
      with normal MRI. Total hypophysectomy was performed in 7 patients who fulfilled
      these criteria. Their results were analyzed retrospectively. RESULTS: The average
      age of the patients was 43 years; there were 7 women. Five adrenocorticotrophic
      hormone-secreting adenomas were proven histologically. Complications occurred in
      6 patients (cerebrospinal fluid fistulas in 6 patients, loss of vision in 1
      patient, meningitis in 5 patients, anterior pituitary insufficiency in 5
      patients, diabetes insipidus in 5 patients). Six patients had sustained remission
      36 months after surgery. CONCLUSION: Total hypophysectomy can be perform ed for
      Cushing's disease with normal MRI. Complications occurs frequently, especially
      cerebrospinal fluid fistulas. Inferior petrosal sinus sampling can be helpful in
      localizing the adenoma allowing hemihypophysectomy and thus reduced morbidity.

PMID- 12058129
TI  - [Cushing's disease and corticotrophic adenoma: results of pituitary
      microsurgery].
AB  - Between November 1994 and June 2001, 194 patients with Cushing's disease
      underwent transsphenoidal surgery: 167 patients had adenomectomy, 14 had ante
      hypophysectomy, 5 had subtotal hypophysectomy, 4 had hemihypophysectomy 4 had
      central hypophysectomy. Complications occurred in 18 patients (9.3%), including 4
      deaths (three were apparently not related to surgery). Remission of disease was
      achieved in 162 of 190 (85.3%) patients analyzed. Surgical failures were
      associated with lack of pituitary adenoma, size of the tumor and invasiveness.
      Among patients with confirmed adenomas, the rate of remission was significantly
      higher (p<0.01) in patients with microadenomas (92.6%) than in patients with
      macroadenomas (66.7%). Reoperation in 6 failures was followed by remission in 4
      cases. The overall remission rate was 87.4%. In the 162 patients with immediate
      success, duration of follow-up was 10.0 +/- 5.9 years (m +/- DS; median=10.0).
      Recurrence of the disease occurred in 24 (14.8%) of 162 patients at a mean 4.8
      years (range: 0.8-12.0 years). Our longest sustained remission is 25.6 years.
      Actuarial analysis indicates that the probability of a patient remaining well 12
      years after surgery is 80.0%. It is 86.2% in microadenomas versus 52.5% in
      macroadenomas and 94.5% in the patients with postoperative hypocortisolism versus
      59.2% in the others.

PMID- 12058131
TI  - [Cushing's disease in children and adolescents].
AB  - Fifty-seven unselected children and adolescents with Cushing's disease underwent
      transsphenoidal exploration and microadenomectomy before their 16th birthday.
      Hypercortisolism was corrected in 42 of the 57 patients (74%). The recurrence
      rate was 17% and the long-term remission rate was 57%. Diagnostic peculiarities
      specific surgical problems and outcome were reviewed. Direct transnasal
      submucosal surgery for Cushing's disease is successful, and pituitary function
      can be preserved in most of these young patients.

PMID- 12058132
TI  - [Clinical recurrence of Cushing syndrome without evidence of tumor recurrence:
      radical hypophysectomy?].
AB  - Outcome following radiation therapy for hormonally-active Cushing adenoma is
      reported. Conventional radiation using 20 to 30 grays improved mass and hormone
      level in 30 to 80% of the patient. Gamma-knife radiosurgery was at least as
      effective. These results are discussed in this review.

PMID- 12058133
TI  - [Unsuccessful surgery of Cushing's disease. Role and efficacy of fractionated
      stereotactic radiotherapy].
AB  - BACKGROUND AND PURPOSE: To optimize and reduce the toxicity of pituitary adenoma
      irradiation, we evaluated the feasibility and effectiveness of fractionated
      stereotactic radiotherapy (FSR) in 51 patients with functional adenoma; 12 of
      them had Cushing's disease. PATIENTS AND METHODS: Eleven females and one male,
      median age: 49 years, 8 of them relapsed and 4 had persistent hormonal secretion
      after surgery. The delivered dose was 50 grays (Gy) (5 x 1.8 Gy/week) using 5
      convergent micro-beams scanning in arc therapy mode. The median planned target
      volume (PTV) receiving 90 to 100% of the total dose was 2,1 cm(3). We used
      relocatable non-invasive stereotactic device Brain Lab, and adapted Linac for
      stereotactic radiotherapy. RESULTS: Nine out of twelve patients (75%) presented
      with complete remission after a median time of 29 months, 3/12 patients with
      partial remission. Actuarial probability to have hormonal persistent secretion
      was 88% at on year, 44% from 3 to 5 years, 22% at 7 years, and 11% to 0% after 7
      years. The 12-corticotroph adenomas were significantly (p=0.007) more
      radiosensitive than 39 non-corticotroph adenomas. Toxicity was significantly
      lower for corticotrope adenoma, with no radio-induced pituitary deficiency and no
      neurological or optic injury. CONCLUSIONS: Combined surgery and FSR appears to be
      safe and effective for treatment of pituitary adenomas. However, long-term follow
      up is required to determine the impact in terms of tumor response and hormone
      deficiency. The focused treated volume obtained by FSR seems more suitable for
      these benign tumours than standard radiotherapy. In addition to this conformal
      approach, the use of standard fractionation reduced the risk of severe damage to
      the optic chiasma, which is sometimes observed after radiosurgery and is inherent
      in single fraction radiotherapy.

PMID- 12058134
TI  - Cushing's disease resulting from pituitary corticotrophic microadenoma. Treatment
      results from transsphenoidal microsurgery and gamma knife radiosurgery.
AB  - Cushing's disease and its associated clinical syndrome reflect the effects of
      excess cortisol on the individual. The cause of Cushing's disease is ordinarily
      an ACTH-secreting benign pituitary adenoma. The diagnosis of Cushing's disease is
      established by sophisticated endocrine testing and comprehensive imaging studies.
      Because of the devastating effects of excess cortisol, therapy that provides
      prompt and effective normalization of serum cortisol is essential. Currently this
      goal is best achieved by transsphenoidal microsurgery. This paper reviews the
      clinical presentation, laboratory analysis, surgical management and outcome in
      patients with Cushing's disease.

PMID- 12058137
TI  - [The genetic basis of premature ovarian failure].
AB  - Premature ovarian failure is defined by the association of amenorrhea, elevated
      levels of serum gonadotropins and hypoestrogenism occuring before the age of
      forty. In a growing number of these cases, genetic disorders have been shown to
      be involved. Cytogenetic abnormalities predominantly concern the X chromosome,
      including Turner syndrome, but also rearrangements such as deletions and X
      autosome translocations. Molecular investigation of these abnormalities has led
      to the identification of a number of candidate genes most of them still having
      unknown functions. Testing for premutation of the FMR1 gene, whose full mutation
      determines the fragile X syndrome, is particularly worthwhile in these patients
      because of its high frequency, not only among the patients with ovarian failure
      but also in the general population. Other, much less frequent mutations have been
      located for example in the gonadotropin and gonadotropin receptor genes and their
      study contributes to the understanding of ovarian physiology. Here we review most
      of the etiologies which have to be taken in account in the genetic screening of
      premature ovarian failure patients.

PMID- 12058136
TI  - [Uterine contractility and reproduction: new perspectives].
AB  - The contractile activity of the nonpregnant uterus plays an important role in the
      human reproduction process. Noticeable variation in uterine contractility occurs
      during the menstrual cycle to meeting some physiologic requirements of the female
      reproductive system. During the follicular phase, stimulation of uterine
      contractions by estrogens fosters sperm transport toward the fertilization site.
      After ovulation, contractility decreases in response to progesterone, a
      phenomenon that is probably involved in the embryo implantation mechanism. The
      comprehension of uterine contractility regulation and physiologic roles has been
      considerably extended during recent years by the development of direct and
      noninvasive assessment tools, in particular, ultrasound. Today, not only the
      artificial stimulation of uterine contractions, aiming at promoting sperm
      transport during the pre-ovulatory phase, but also their attenuation to provide
      optimum conditions for embryo implantation during the luteal phase, represent
      innovating, promising issues in the optimization of assisted reproduction
      treatments.

PMID- 12058138
TI  - [Great elongation of uterine cervix: retrospective study of 20 cases].
AB  - BACKGROUND: The aim of the study was to evaluate the safety and efficacy of the
      Musset Poitout surgical procedure consisting in an anterior uterosacral ligament
      transposition and a cervix amputation. The main indication is an uterovaginal
      prolapse with an isolated elongation of the cervix. METHODS: A retrospective
      consecutive series of 20 women with an elongation of uterine cervix undergoing
      Musset Poitout procedure over a 10 year period between 1990 and 2001 with
      analysis of per and post operative complications and success. Four Kelly urethral
      plications were performed in the same time. The patient's ages, time under
      anesthesia, change in hemoglobin, days of hospitalization, medical illnesses,
      complications and follow-up were assessed. Failure was defined as a symptomatic
      elongation of the cervix or a third degree hysterocele on examination. RESULTS:
      and discussion. The median age of Musset Poitout procedure was 43.9 years (range
      23-83). General anaesthesia could be performed in all patients. Mean operation
      time was 67 minutes (range 40-130). No major per or post operative complications
      occurred. The average of post-operative bladder cathetherisation was 3.65 days,
      the average hospital stay was 6.3 days. Complications were insignificant: urinary
      tract infection in 2, voiding dysfunction in 2. All the patients but 2 were
      followed for a mean 59 months (range 6-127). There was one recurence (5.5%).
      CONCLUSION: In this preliminary assessment the Musset Poitout procedure offered
      significant avantages in a genital prolapse with elongation of the cervix.

PMID- 12058139
TI  - [Microvolume dosage of lactate in cord blood for the evaluation of the neonatal
      well-being].
AB  - A preliminary experience about a new microvolume lactate meter (Lactate Pro) is
      reported from 200 consecutive term deliveries. Comparison between lactate and pH
      in umbilical artery revealed a significant negative correlation between the two
      variables (r=-0.0693; p<0.0001). For the diagnosis of acidosis (pH<7.15) a
      lactate cutoff value at 6 mmol/l had a sensitivity of 50% and a specificity of
      92% in a population with a prevalence of 8%. The study also demonstrated a better
      correlation between the concentrations of lactate and the base excess from 44
      cord blood samples in high risk deliveries (r=0.837; p<0.0001). A lactate value
      higher than 6mmol/L predicted a metabolic acidosis (BE>- 8 mmol/l) with a
      sensitivity of 50% and a specificity of 94% from a collective with a prevalence
      of 16%. Considering the simplicity of the method, lactate measurements in cord
      blood could be extended to all birth centers for a systematic evaluation of the
      fetal condition in combination with the APGAR score. According to the minimal
      sampling volume (5 microliter) and the better prediction of metabolic acidosis
      this new method could replace the determination of the pH on fetal scalp.

PMID- 12058140
TI  - [Severe post-partum hemorrhage: descriptive study at the Robert-Debre Hospital
      maternity ward].
AB  - OBJECTIVE: To analyze the prevalence, cause, treatment, and risk factors of
      severe post-partum hemorrhage (transfusion, surgery, radiology) observed at the
      maternity ward of the Robert-Debre Hospital, Paris. Method. This retrospective
      cohort was collected from a database including 19182 deliveries from 1992 to
      1998. The entire medical file was reviewed in cases of severe hemorrhage.
      RESULTS: The prevalence of severe post-partum hemorrhage was 23 per 10,000
      deliveries (44 patients). Transfusion was performed in 44/44 and hysterectomy in
      3/44. Three patients were transferred to the intensive care unit. There were no
      deaths. At multivariate analysis, risk factors for severe post-partum hemorrhage
      were: abnormal placental insertion (OR=7.2; 95CI: 2.18-18.3), cesarean (OR=5.8;
      95CI: 2.9-11.6), multiple pregnancy (OR=3.2; 95CI: 1.3-7.8), prematurity (OR=3,
      95CI: 1.5-6.2), hypertension (OR=2.9; 95CI: 1.3-6.3). Twenty-six percent of the
      patients had no risk factors. CONCLUSION: The prevalence of severe pot-partum
      hemorrhage is low in our experience. The methodology used for this retrospective
      cohort does not enable an explanation. Intensive obstetrical care is necessary in
      case of abnormal placenta insertion. In 10 out of 44 cases, severe post-partum
      hemorrhage occurred in a context of insufficient monitoring, late or erroneous
      diagnosis, or incorrect treatment.

PMID- 12058141
TI  - [Krukenberg tumor: 9 cases report].
AB  - INTRODUCTION: The Krukenberg tumor is a mysterious ovarian metastasis of
      digestive tract cancer accounting from 1 to 2% of all ovarian tumors. PATIENTS:
      and method. We report a series of 9 patients with Krukenberg tumors treated at
      the Casablanca University Hospital between 1982 and 1999. RESULTS: Mean age of
      the patients was 44 years. Pelvic signs predominated over digestive signs.
      Bilateral forms were more frequent. Surgical or medical treatment were given. The
      histological diagnosis is based on the presence of signet-ring cells associated
      with a pseudosarcoma stroma. The primary tumor was found in 50% of the cases.
      Prognosis is always unfavorable. All authors underline the gloomy prognosis of
      this tumor with fatal outcome in one year. Early diagnosis and complete resection
      is the only hope. CONCLUSION: Krukenberg tumor is an ovarian metastasis of
      digestive tract cancer. The only hope for improved prognosis is to search for
      ovarian metastasis in all cases and prophylactic ovariectomy in women over 40
      with digestive tract cancer.

PMID- 12058142
TI  - [Uterine rupture on unscarred uterus following labor induction for 2(nd)
      trimester termination of pregnancy with oral misoprostol: conservative
      management].
AB  - Uterine rupture occurred at 25 weeks amenorrhea during pregnancy termination by
      misoprostol for fetal polykystosis. Rupture occurred on an unscared uterus after
      administration of significant accumulated doses of oral misoprostol (1400 g). The
      patient was managed conservatively and carried a subsequent pregnancy six months
      after the intervention. This accident occurs in 0.1% to 1% of the cases (0.59% in
      our experience) and only rare cases have been attributed to the use of
      misprostol. Clinicians should be particularly careful in patients with prior
      cesarean section or a weakened uterus.

PMID- 12058143
TI  - [Post-partum cerebral thrombophlebitis: three cases].
AB  - Post-partum cerebral thrombophlebitis is a rare accident (1/3000 to 1/10000
      births). Symptoms vary and may be misleading. We report three cases of cerebral
      thrombophlebitis occurring during the pospartum period where diagnosis was based
      on clinical signs and imaging data (computed tomography and cerebral
      angiography). Heparin therapy led to good outcome in all three cases. Heparin
      therapy has been controversial for these patients but recent work has shown
      improvement in this severe conditions with very poor prognosis.

PMID- 12058144
TI  - [Cerebral vascular malformations and pregnancy: obstetrical and anesthetic
      management].
AB  - Obstetrical management of women known to have a cerebral vascular malformation is
      controversial. The risk of cerebral hemorrhage during pregnancy is difficult to
      assess. We report thirteen cases of pregnancy in women with known cerebral
      vascular malformations who had or had not undergone surgical treatment. The
      effect of pregnancy on these malformations and corresponding obstetrical care
      described in the literature were studied. Our conclusion is that the risk of
      bleeding from cerebral arteriovenous malformations is not significantly increased
      during pregnancy whereas the risk of cerebral hemorrhage is slightly increased at
      the end of pregnancy, but unchanged during labor and delivery, in women with
      arterial aneurysms. There is no reason to advise against pregnancy in most cases
      and vaginal delivery is often possible unless there is a risk of dystocia.

PMID- 12058145
TI  - [Iniencephaly and early prenatal diagnosis].
AB  - Iniencephaly is a rare malformation of the base of the skull. The brain is
      involved and prognosis is almost invariably lethal. Diagnosis is now possible
      with morphologic ultrasound, and lead to propose induced abortion. We describe a
      new case report with early prenatal diagnosis that allowed induced abortion at
      the term of 14 weeks.

PMID- 12058146
TI  - [Hydatic cyst of the fallopian tube: a case report].
AB  - A 37-year-old woman was seen for pelvic pain. Ultrasonography and laparoscopy led
      to the diagnosis of bilateral hydrosalpinx. Analgesics and antibiotics were given
      several times but the clinical picture worsened. Laparotomy was performed and
      disclosed bilateral hydatidosis of the fallopian tubes requiring bilateral
      salpingectomy. Postoperatively, hydatic serology was strongly positive and a
      calcified hydatic splenic cyst was identified. Medical treatment with albendazole
      was prescribed for these multiple localizations of hydatid cysts.

PMID- 12058148
TI  - [Comments on the Perruche decree].

PMID- 12058149
TI  - Triptorelin pamoate (Trelstar).

PMID- 12058150
TI  - Tazarotene (tazorac) for acne.

PMID- 12058151
TI  - Arrhythmias from droperidol?

PMID- 12058152
TI  - Giving ourselves a pat on the back.

PMID- 12058153
TI  - Breast cancer survivorship: are African American women considered? A concept
      analysis.
AB  - PURPOSE/OBJECTIVE: To apply Rodger's (1989) evolutionary view of concept analysis
      to the term "cancer survivorship" with a heightened focus on breast cancer and
      African American women. DESIGN: Qualitative, concept analysis. DATA SOURCES: 50
      references from the disciplines of nursing and medicine. DATA SYNTHESIS: This
      analysis revealed that the concept of cancer survivorship is unique, evolving,
      and based on the meaning individuals give to a diagnosis of cancer and their
      experiences of living beyond the diagnosis. CONCLUSIONS: The concept of breast
      cancer survivorship can be operationally defined as the process of living through
      the cancer experience beyond a breast cancer diagnosis. A crucial need exists to
      explore the meaning of cancer survivorship among African American women as a
      basis for culturally competent care. IMPLICATIONS FOR NURSING: Nurses and other
      healthcare professionals must comprehend the meaning of breast cancer
      survivorship and its implications for cancer survivors. The meaning of cancer
      survivorship to African American and ethnic minority women must be explored.
      Culturally relevant cancer survivorship education and care should be provided for
      African American women and other cancer survivors of ethnic minorities as well as
      those involved in the women's social and healthcare world. Nurses and healthcare
      professionals must continue to advocate for health policies to improve the lived
      experiences of all cancer survivors.

PMID- 12058155
TI  - Incorporating multiculturalism into oncology nursing research: the last decade.
AB  - PURPOSE/OBJECTIVES: To use the Oncology Nursing Society's cultural competence
      guidelines to review research studies conducted by oncology nurse researchers
      with racial and ethnic minorities and published in the Oncology Nursing Forum
      during 1990-2000. DATA SOURCES: Using selected key words (e.g., cultural
      competence, cultural diversity, multiculturalism, minorities, African
      American/Black American, Hispanic/Latino, Asian/Pacific Islander, Native
      American/Alaskan Natives) the authors identified 27 studies that met the
      inclusion criteria for review. Case studies, sponsored lectureships, review
      articles, commentaries, editorials, and the like were excluded. DATA SYNTHESIS:
      Within the context of the cultural competence guidelines, the primary strengths
      included sufficient background information and literature to establish the
      existence of the problem in the targeted culture, use of conceptual and
      theoretical frameworks to guide the study, identification of salient study
      limitations, and recommendations for dissemination of the findings to a general
      audience. Limitations included discussion of culture beyond the background and
      literature review, consideration of potential ethical concerns the target
      population may have about the methods to be used, inclusion of racial and ethnic
      minorities in the design and implementation of the study, and implications for
      oncology nursing education. CONCLUSIONS: Although much has been gleaned from
      previous oncology nursing research published from 1990-2000, more fully
      incorporated content related to cultural competence is needed. This is needed
      particularly in studies specifically targeting racial and ethnic minority
      populations. IMPLICATIONS FOR NURSING: Including cultural competence when
      designing and reporting research has a greater potential to inform oncology
      nursing practice, design future research studies, strengthen existing nursing
      curricula, and help to shape health policy related to racial and ethnic minority
      populations. The Oncology Nursing Society Multicultural Outcomes: Guidelines for
      Cultural Competence provides guidance for enhancing the next generation of
      oncology nursing research with ethnically and culturally diverse populations.

PMID- 12058154
TI  - Cancer survivorship research among ethnic minority and medically underserved
      groups.
AB  - PURPOSE/OBJECTIVES: To review the current state of knowledge about the impact of
      cancer on ethnoculturally diverse and medically underserved survivors. DATA
      SOURCES: MEDLINE, CancerLit, and Psychlit searches from 1966-present were
      conducted to locate articles about survivorship outcomes among minority and
      underserved populations. DATA SYNTHESIS: 65 articles were identified and grouped
      into one of four content areas: physiologic; psychosocial; health services,
      patterns of care, and quality of care; and health-promoting behaviors and
      lifestyles. CONCLUSIONS: Despite limited information, researchers found a
      consistent theme: the need to recognize and address the socioeconomic and
      cultural variables that affect adaptation to and survival from cancer among
      diverse groups of survivors. IMPLICATIONS FOR NURSING: The researchers found
      specific variations in risk for, response to, and recovery from cancer that
      provide direction for changes in nursing practice that may reduce the burden of
      cancer in these often vulnerable populations.

PMID- 12058156
TI  - Well-being in Hispanic and non-Hispanic white survivors of breast cancer.
AB  - PURPOSE/OBJECTIVES: To test a well-being model on Hispanic and non-Hispanic white
      survivors of breast cancer by comparing responses about variables hypothesized to
      predict well-being. MAIN RESEARCH VARIABLES: Healthcare orientation, uncertainty,
      social support, resourcefulness, self-esteem, and well-being. DESIGN: Descriptive
      and comparative. SAMPLE: 50 Hispanic and 50 non-Hispanic white women who
      completed treatment for breast cancer and were disease-free. SETTING: Regional
      cancer center in southwestern United States. METHODS: Subjects completed the
      Psychosocial Adjustment to Illness Scale-Health Care Orientation Subscale, Mishel
      Uncertainty Illness Scale, Personal Resource Questionnaire, Self-Control
      Schedule, Self-Esteem Inventory, and Index of Well-Being. FINDINGS: Both groups
      of women reported high well-being. Sample characteristics were not related
      significantly to well-being in either group. No statistically significant
      differences were found between Hispanic and non-Hispanic white women on any
      variables. CONCLUSIONS: Comparison of well-being models revealed similarities
      between the two groups, including variables entering each regression equation,
      and explained variance. Further research is needed to explore whether
      commonalities in women's responses to breast cancer exist independent of
      ethnicity. IMPLICATIONS FOR NURSING: Nurses should continue encouraging both
      Hispanic and non-Hispanic white women to share concerns and seek information from
      healthcare providers while strengthening feelings of self-worth because these
      factors directly affect well-being.

PMID- 12058157
TI  - Modifying a breast cancer risk factor survey for African American women.
AB  - PURPOSE/OBJECTIVES: To evaluate a breast cancer risk factor survey for use with
      African American women. DESIGN: Two focus groups consisting of women randomly
      selected from the patient population of Henry Ford Health System in Detroit, MI.
      SETTING: A large, vertically integrated, private, nonprofit health system.
      SAMPLE: Focus Group I consisted of 11 African American women aged 18-50, with a
      mean age of 41 years. Focus Group II consisted of nine African American women
      aged 51 and older, with a mean age of 60.9 years. METHODS: A qualitative approach
      was used to gather and interpret the focus group data. MAIN RESEARCH VARIABLES:
      Perceptions of a breast cancer risk factor survey and perceptions of breast
      cancer risk factors. FINDINGS: The focus group participants suggested ways to
      improve the survey. Women in the younger age group appeared to lack awareness
      regarding breast cancer risk factors. Women in the older age group reported not
      knowing their family health histories. CONCLUSIONS: Based on comments made by the
      focus group participants, the survey was modified substantially. Breast cancer
      risk factors were perceived differently by women in the two age groups.
      IMPLICATIONS FOR NURSING: Results of a survey of a large, ethnically diverse
      sample of women could inform the development of culturally and age-appropriate
      nursing interventions designed to address breast cancer risk perceptions and
      enhance the likelihood of adherence to recommended mammography screening
      guidelines.

PMID- 12058158
TI  - Screening behaviors among African American women at high risk for breast cancer:
      do beliefs about god matter?
AB  - PURPOSE/OBJECTIVES: To examine the relationship between beliefs about God as a
      controlling force in health and adherence to breast cancer screening among high
      risk African American women. DESIGN: Cross-sectional cohort. SETTING: In-person
      interviews in rural, southeastern Louisiana and telephone interviews conducted at
      the University of Utah. SAMPLE: 52 females who were members of a large kindred
      with a BRCA1 mutation; no subjects had breast cancer. METHODS: Survey through in
      person or telephone interviews. MAIN RESEARCH VARIABLES: Belief in God as a
      controlling agent over health measured by the God Locus of Health Control (GLHC)
      scale; screening behaviors measured by self-report. Adherence was based on
      consensus-approved recommendations for BRCA1 carriers or women at risk of being
      carriers. FINDINGS: Bivariate analysis indicated that presence of a primary care
      provider and low GLHC scores were associated with seeking clinical breast
      examination (CBE) and mammography. With the variable "presence of a primary care
      provider" excluded, GLHC scores were inversely associated with seeking CBE and
      mammography. CONCLUSIONS: African American women at increased risk for breast
      cancer and with high GLHC scores may have a decreased inclination to adhere to
      CBE and mammography recommendations. IMPLICATIONS FOR NURSING: Assessing
      religious and spiritual beliefs and incorporating belief systems into education
      and counseling sessions may improve understanding and acceptance of presented
      material.

PMID- 12058159
TI  - The influence of social support on breast cancer screening in a multicultural
      community sample.
AB  - PURPOSE/OBJECTIVES: To examine the relationship between women's reported social
      support and their adherence to recommended breast cancer screening guidelines.
      DESIGN: Descriptive, cross-sectional survey. SETTING: Community women's
      organizations throughout the San Francisco Bay Area. SAMPLE: 833 mostly low
      income women with a mean age of 46.2 years from three racial or ethnic groups
      (i.e., Latina, Caucasian, and African American) who were not breast cancer
      survivors. METHODS: Social support was measured with a five-item, four-point,
      Likert scale developed for the study (Cronbach's alpha = 0.7248). Adherence to
      screening guidelines was measured by asking frequency of performing breast self
      examination (BSE) and frequency of obtaining a clinical breast examination (CBE)
      and a mammogram. Research assistants and leaders of women's organizations
      conducted the survey in work and community settings. MAIN RESEARCH VARIABLES:
      Social support, performance of BSE, obtaining a CBE and a mammogram, income,
      education, spoken language, and level of acculturation. FINDINGS: Higher levels
      of social support were related to higher income and higher education. Lower
      levels of social support were associated with being Latina, completing the survey
      in Spanish, and being born abroad. Women who did not adhere to screening
      guidelines (for BSE or CBE) reported less social support. CONCLUSIONS: Social
      support is associated with adherence to breast cancer screening guidelines.
      IMPLICATIONS FOR NURSING: Nurses should assess women's levels of social support
      as a factor when evaluating adherence to breast cancer screening guidelines.

PMID- 12058160
TI  - Population-based cancer screening.
AB  - PURPOSE/OBJECTIVES: To provide an overview of current issues surrounding the
      prevention of and screening for lung, breast, cervical, colorectal, ovarian,
      prostate, and skin cancer. DATA SOURCES: Original research, review articles, and
      published guidelines. DATA SYNTHESIS: Although morbidity and mortality rates have
      decreased for these cancers, prevention and early detection still require
      increased funding and research. CONCLUSIONS: More behavioral scientists must be
      trained in prevention and early detection of cancer, and increased research
      funding is necessary to encourage advances in primary and secondary prevention.
      IMPLICATIONS FOR NURSING: Oncology nurses should incorporate appropriate
      prevention and early-detection strategies into practice.

PMID- 12058161
TI  - Learning and support preferences of adult patients with cancer at a comprehensive
      cancer center.
AB  - PURPOSE/OBJECTIVES: To identify content items for an inclusive education
      curriculum for adult patients with cancer, as well as describe their learning and
      support preferences, determine the level of information provided to them, and
      assess the patients' interest in potential new services. DESIGN: Exploratory,
      descriptive survey research. SETTING: A National Cancer Institute-designated
      Comprehensive Cancer Center. SAMPLE: All consenting adult patients with cancer
      who had appointments in the outpatient care setting during a two-week period (N =
      1,310). METHODS: A 3-phase study identified core components of an inclusive
      educational curriculum, conducted structured interviews of patients with cancer,
      and validated findings in a selected sample. FINDINGS: The surveys were completed
      and returned by 48% (n = 625) of the patients. The most favored method for
      learning about all cancer topics was discussions with physicians (66%). Other
      preferred methods included brochures or booklets provided by physicians or nurses
      (33%), discussions with nurses (34%), self-selecting print media from information
      displays (20%), and talking with other patients with cancer (14%). Statistically
      significant differences in learning preferences were found among subgroups
      defined by age, gender, and education. CONCLUSIONS: Patients preferred
      interactive, interpersonal communication with physicians or nurses. In addition,
      the prevailing method of education delivery for patients with cancer was
      providing print materials that support and enhance knowledge shared in the
      patient-healthcare team communication. IMPLICATIONS FOR NURSING: This study
      confirms the importance of the learning and support preferences of patients with
      cancer. To implement a successful education program for their patients, nurses
      must be aware of patients' preferences for learning new information. Time must be
      set aside for one-on-one communication with patients, and print materials must be
      easily accessible to healthcare providers to support the patient-education
      process.

PMID- 12058163
TI  - A Promoter Overlapping with that of nodF is Responsible for a New RNA Molecule
      Transcription in Rhizobium leguminosarum.
AB  - The expression of nod genes of rhizobia is controlled at the transcriptional
      level in a complicated way. In this work, a new promoter, which is responsible
      for an RNA molecule transcription in the opposite direction to that of nodF, was
      identified in Rhizobium leguminosarum. This new promoter was characterized to
      overlap with that of nodF, and the size of px(2), the RNA molecule initiated from
      this promoter was determined to be of approximately 0.72 kb in length. The study
      on px2 showed that its transcription depended on the Escherichia coli sigma(70)-
      like factor of Rhizobium leguminosarum, and that the in vitro transcription of
      px(2) was inhibited by Px, a newly identified regulatory protein in our lab. The
      involvement of px(2) in the regulation of nod gene expression is suggested.

PMID- 12058164
TI  - Structure and Conformation Behavior of a Glucan from Spores of Ganoderma lucidum
      (Fr.) Karst.
AB  - A novel polysaccharide designated as beta-D-glucan LB-NB, [alpha](D)(21) 
      24.52(0)(c =0.81, H(2)O)and Mr 4.7x10(4), was isolated and purified from a 0.5
      mol/L sodium hydroxide extract of the sporoderm-broken spores of Ganoderma
      lucidum. The results of NMR experiments, total hydrolysis, methylation analysis
      and Smith degradation of LB-NB showed that it possesses a backbone consisting
      of(1right curved arrow 3)- beta-D-glucosyl residues, about two out of nine
      glucosyl residues being substituted at O-6 by single glucosyl groups. The
      conformational behavior of LB-NB was studied. Measurements by specific rotations
      and viscometry showed that the glucan LB-NB takes an ordered structure in water
      or lower concentration(<0.05 mol/L)alkaline solution and dissolves as random coil
      in higher concentration(>0.1 mol/L)alkaline solution or in dimethyl
      sulfoxide(Me(2)SO). The ordered conformation melts into flexible chains with the
      increase of the concentration of alkali or the V(DMSO)(v/v)of H(2)O-Me(2)SO
      mixture. The former dissociation is reversible and the later is irreversible. The
      complex-formation with Congo red indicated that the LB-NB takes neither triple
      stranded helical nor randomly coiled conformation in neutral or slightly alkaline
      solution, and most probably, it should contain single helical structure in
      aqueous solution. According to immunological test, the LB-NB showed remarkable
      activity of stimulating the proliferation of T-Cells in vitro, giving a good
      example for Kulicke's statement.

PMID- 12058166
TI  - Screening of Genes Encoding Nuclear Localization Signal in a Mouse Embryonic cDNA
      Library.
AB  - A genetic screening system was established previously for the cloning of gene
      fragments encoding nuclear localization signals (NLS). In the current study, the
      system was improved and its ability to distinguish nuclear and cytoplasm
      localized proteins was verified by inserting a known NLS-encoding gene. A mouse
      10.5-d pc embryonic cDNA library was then inserted into the cloning site of the
      screening vector and 22 out of 10(4) clones were shown to be positive after
      screening using the system. The cDNA inserts of some of these clones were
      sequenced, and typical and untypical NLS were identified. The nuclear localizing
      activity of the cDNA inserts was further verified using the GFP fusion protein
      system. So, the system is useful in the cDNA library screening of genes encoding
      NLS-bearing proteins.

PMID- 12058165
TI  - Expression of Human Soluble CD40 Ligand in Pichia pastoris and Its Effects on
      Dendritic Cells and Malignant B Cells.
AB  - CD40 ligand (CD40L) is a member of the tumor necrosis factor (TNF) superfamily
      and is expressed primarily on the activated CD4( )T lymphocytes. The CD40
      molecule, the cognate receptor of CD40L presents on many immunocytes such as B
      lymphocytes, dendritic cells (DCs) as well as on some neoplastic cells.
      Triggering of CD40 through CD40L plays a central role in the initiation and
      regulation of the human immune response. In order to further investigate the
      possible biological roles of CD40 signaling triggered by CD40L, we subcloned the
      DNA fragment encoding the extracellular region of human CD40L into the pSK
      plasmid. After being sequenced, the target fragment was introduced into the
      pPICZalphaA plasmid to construct the pPICZalphaA-sCD40L expressing vector which
      was then transduced into Pichia pastoris GS115 cells by electroporation. The
      tansformant expressed sCD40L in culture supernatants with a maximum yield of
      about 35 mg/L. Furthermore, we found that the recombinant human soluble CD40
      ligand (rhsCD40L) could effectively induced human peripheral blood
      monocytes(PBMCs) in vitro in the absence of TNFalpha into dendritic cells (DCs)
      with the typical morphology and special surface markers of dendritic cells
      including CD1a, CD80, CD83, and HLA-DR etc. To our surprise, the rhsCD40L also
      could inhibit directly in vitro proliferation of the CD40-positive multiple
      myeloma cell line XG-2 and the B lymphoma cell line Daudi significantly at an
      optimal concentration from 2.5 to 15.0 mg/L, while CD40 negative ovarian
      carcinoma cell lines, SKB and SKR, were not effected by either high or low
      concentration of rhsCD40L. Moreover, rhsCD40L had the same effects as CD40L
      transfected cell in inducing XG2 cell apoptosis. Our results demonstrated that
      functional human soluble CD40L could be successfully expressed in the Pichia
      pastoris system and that the recombinant human soluble CD40L might be a potential
      immune adjuvant and a new powerful molecule for tumor bio-therapy.

PMID- 12058167
TI  - ZNC(C)PR Induces Phosphorylation of CREB in Rat Hippocampus.
AB  - ZNC(C)PR can facilitate the learning and memory in rat. Transgenic experiments
      have revealed that long-term memory depended on cyclic AMP-response element
      binding protein, CREB. CREB phosphorylation at serine-133 is essential for it's
      transcriptional activity. Here, it was demonstrated that ZNC(C)PR could induce
      CREB phosphorylation at serine-133 in both rat hippocampus and rat hippocampus
      slices. ZDC(C)PR antagnist of ZNC(C)PR , PTX(inhibitor of G(o)/G(I) protein
      coupled receptor), GF109203x(inhihitor of PKC), PD98059( inhibitor of MAPK ) but
      not KN-62(inhibitor of CaMKII) could inhibit the phosphorylation of CREB induced
      by ZNC(C)PR.

PMID- 12058168
TI  - Enhancing Penicillin G Acylase Stability by Site-directed Mutagenesis.
AB  - To improve the stability of penicillin G acylase(PGA) from Bacillus megaterium, a
      three-dimensional model of B.megaterium PGA was constructed based on crystal
      structure of penicillin G acylase from E.coli using PMODELING program. The
      mutation of Lys at beta427 and 430 to Ala was predicted to enhance the stability
      of PGA in acidic or organic solvent environment. The results showed that 2 mutant
      PGA had similar specific activity and Km as the parent PGA. Their optimum pH
      dropped 0.5 pH units. The stability of Lys430Ala was enhanced obviously at pH
      5.2. The half lives of Lys427Ala and Lys430Ala were improved by 60 % and 166 %,
      respectively, in comparison with the parent PGA.

PMID- 12058169
TI  - Cloning and Functional Analysis of ALS Family Genes from Candida albicans.
AB  - With a 0.5 kb probe of CX2, distribution of CX2 tandem repeats was studied in
      different C.albicans strains. Results suggest that all the C.albicans strains
      tested contained the tandem repeat. In order to verify if the expression of CX2
      was hyphal specific, its expression was analyzed under various inductive and non
      inductive conditions. With CX2 0.5 kb probe, Northern hybridization analysis
      confirmed that it was specifically in hyphae. The result of chromosomal
      localizationtion and genomic Southern blot analysis suggested that there were
      other genes containing the tandem repeat besides of ALS1. A C.albicans s genomic
      DNA library was screened with the CX2 0.5 kb probe and several positive
      recombinant lambda phages were obtained. After endonuclease identification,
      subcloning, and sequence analysis, several ALS family genes were cloned. No.1
      lambda phage DNA contained ALS4, No.4 lambda phage DNA contained ALS1, No.6
      lambda phage DNA contained ALS3. To study the role of ALS family genes in yeast
      hyphal transition, als1/ALS1 mutant was constructed by homologous recombination.
      The ability to form hyphae was tested in different inductive culturing
      conditions. Defective hyphal growth were observed in some solid media.

PMID- 12058170
TI  - De Novo Interpretation of MS/MS Spectra and Protein Identification via Database
      Searching.
AB  - Peptide sequencing via tandem mass spectrometry(MS/MS)is one of the most powerful
      tools in proteomics to identify proteins. A new algorithm was developed for de
      novo interpretation of MS/MS spectra using graph theory and dynamic alignment
      between real spectra and theoretical spectra. The trustworthy peptides from de
      novo interpretation were used in protein identification via database searching. A
      high throughput statistical analysis of SwissProt and TrEMBL protein databases
      showed that it's enough to identify a protein in database with three sequence
      tags of four amino acid residues, two sequence tags of five amino acid residues
      or one sequence tag of eight amino acid residues.

PMID- 12058171
TI  - On the Mechanism of Growth Inhibition of Epiregulin in A431 Epidermal Carcinoma
      Cells.
AB  - Preliminary investigation on the mechanism of the growth inhibition by
      recombinant epiregulin(EPI)of epidermal carcinoma cell A431 is reported. Northern
      blotting indicated that the mRNA level of cyclin dependent kinase(CDK)inhibitor,
      p21(WAF1/CIP1), was increased significantly after stimulation of the recombinant
      epiregulin protein. Luc reporter revealed that STAT1 could bind the promoter
      region of p21 in response to the EPI signal. Flow cytometry assay showed that the
      EPI-induced growth inhibition was not related to the apoptosis. The above results
      indicate that the EPI-induced cell growth inhibition might result from the STAT1
      stimulated expression of p21, leading to the G1 arrest.

PMID- 12058172
TI  - Influence of An Adenosine Receptor Antagonist on Neurotransmitters in
      Parkinsonian Mice.
AB  - The effects of the adenosine A(2a) receptor antagonist, Quinazoline, on the
      monoamine transmitters NA, DA, 5-HT and 5-HIAA was studied using fluorecent
      method, and the influence of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
      and Quinazoline (CP66713) on the GABA positive reaction cells in globus pallidus
      was determined by immunohistochemistry technique in MPTP treated Parkinsonian
      mice. The results showed that MPTP decreased the content of DA, 5-HIAA and
      increased 5-HT, GABA obviously(pp<0.01). Quinazoline functioned opposite the
      action of MPTP, increasing the content of DA, 5-HIAA and decreasing the 5-HT.
      Quinazoline also reduced the GABA-positive reaction cells in globus pallidus of
      control mice and maintained the level of GABA-positive reaction cells of globus
      pallidus in MPTP treated mice, making it similar with the level of control.

PMID- 12058173
TI  - Difference between Biological Activities and Secondary Structures of Expression
      Product of atpE Gene from Broad Bean and Maize Chloroplast.
AB  - The chloroplast atpE genes from broad bean and maize were overexpressed in
      E.coli, respectively. After proper refolding and purification, two types of
      epsilon-subunit proteins with biological activity were obtained. When
      reconstituted with CF(1)(-epsilon)from different chloroplast ATPase, the effects
      of the reconstructed epsilon-subunit protein of maize CF(1) to the Ca(2+)-ATPase
      activity of epsilon-deficient CF(1) and to the proton leakage through CF(0) were
      markedly stronger than that of broad bean CF(1). It was also observed that the
      enhancing effect of maize epsilon-subunit protein to the chloroplast
      photophosphorylation activity was greater than that of broad bean epsilon-subunit
      protein. The results indicate that (1)the inhibition of epsilon-subunit is
      closely related to the its affinity with other parts of CF(1) (2)both functions
      of epsilon-subunit as inhibitor of ATPase and as proton pathway are closely
      linked. The circular dichroism was performed to show the differences in their
      secondary structure of these epsilon-subunit proteins based on the deduced
      primary sequences. Unconstrained analysis of the CD spectrum for the maize
      epsilon-subunit protein gave 22.6% alpha-helix, 30.6% beta-sheet, 9.3% beta-turn,
      and 37.7% unordered structure and 31.4%alpha-helix, 22.3% beta-sheet, 13.8% beta
      turn, and 32.4% unordered structure for the epsilon-subunit from broad bean.

PMID- 12058174
TI  - Identification of Novel Regulatory Elements of Human Stem Cell Factor Gene in MCF
      Cell.
AB  - Human stem cell factor(hSCF)is a pluripotent growth factor that regulates
      proliferation, differentiation and migration of certain mammalian stem cells,
      such as primordial germ cells etc. It is shown that hSCF and its receptor are
      commonly co-expressed in human breast cancer cells. Up to now, the definite
      regulatory mechanism of hSCF gene in breast cancer cells is unclear, except that
      its 5'flanking sequence contains essential elements for regulating transcription.
      To localize the regulatory elements responsible for the regulation of the hSCF
      gene, we performed transient transfection study in MCF cells, with a series of
      luciferase reporter gene constructs, containing different 5x end deletions of
      hSCF gene. This study indicates that the region of -1190 -853 significantly
      enhanced the luc gene expression, while the region of -339 -162 inhibited the
      expression. Eletrophoretic mobility shift assay confirmed that MCF nuclear
      extract proteins bound to both -1190 -853 and -339 -273 regions, forming specific
      DNA-protein complexes, indicating that there were nuclear protein binding sites
      in these regions. The results suggest that both -1190 -853 and -339 -273 DNA
      fragments of the hSCF 5'flanking sequence may be novel regulatory elements, and
      may play a role in the regulation of hSCF gene expression in MCF cells.

PMID- 12058175
TI  - Transplastomic Plants Homoplasmic for Foreign Transgenes.
AB  - Scientists pay more and more attention to the research on plastid engineering for
      its following advantages foreign genes can be integrated site-specifically into
      the plastid genome (plastome) there are no position effects as experienced with
      random insertion of transgenes in nuclear transformation pollen-mediated
      dispersion of transgenes can be avoided because chloroplasts are maternally
      transmitted gene silencing does not occur in plastids and therefore transgene
      expression is stable in progeny of transplastomic plants and the high ploidy
      level of the plastome in leaf cells makes high levels of transgene expression
      feasible. At the same time, however, the highly polyploid plastome makes it
      difficult to get transplastomic plants homoplasmic for foreign transgenes. In
      this work, chloroplast transforming vector pTRCH205, which carries two psbA5'
      nifH-psbA3'and Prrn-aadA-TpsbA cassettes flanked by plastid DNA sequence to
      target their insertion between psbA and trnK operons, was constructed. Plastid
      transformation of Nicotiana tabacum was carried out by the biolistic delivery of
      transforming plasmid pTRCH205 DNA into leaf cells. Integration of nifH and aadA
      by two homologous recombination events via the flanking ptDNA sequences, and
      selective amplification of the transplastomes on MS medium with high
      concentration of spectinomycin, yielded resistant cell lines. All the independent
      transplastomic lines were subjected to three additional rounds of regeneration
      and were subcultured for 6--10 times through stem sections on MS medium
      containing 500 mg/L spectinomycin, to obtain homoplasmic tissues. The results of
      PCR assay and Southern blot hybridization, probed with 0.9 kb BglII/SnaBI
      homologous fragment, indicated that foreign genes had been integrated into the
      plastomes of transgenic plants, which finally became homoplasmic for foreign
      transgenes.

PMID- 12058177
TI  - A Recombinant Monomeric Human Insulin Mutant with Resistance to Trypsin Design,
      Preparation and Characterization.
AB  - By using a gapped duplex DNA method, the four amino acids on the B chain of
      insulin, i.e. B22Arg, B28Pro, B29Lys and B30Thr, were mutagenized simultaneously
      into B22Asp, B28Lys, B29Pro and B30Lys, respectively. The recombinant B22Asp
      B28Lys B29Pro B30Lys human insulin was obtained simply by the treatment with
      trypsin of the precursor that was expressed in yeast. This human insulin analog
      had only 6% of receptor binding activity as that of the porcine insulin, but
      retained 50% of in vivo biological activity, compared with the latter. The self
      association ability of the mutant measured through FPLC gel filtration
      chromatography showed that it was in monomeric state. As a monomeric insulin
      analog with resistance to the trypsin digestion, this compound may be promising
      in practical application.

PMID- 12058176
TI  - Cloning and Expression of Insulin Receptor Ligand-binding Domains.
AB  - Insulin receptor is a transmembrane protein consisting of four subunits, that
      form a heterotetramer(alpha(2)beta(2))with molecular weight of 350 kD. Because
      the extracellular subunit(alpha)consists of 731 residues and a cysteine-rich
      domain, it is difficult to express and crystallize such a large ligand-binding
      subunit, thus hampering further study on "insulin-receptor" complex. Based on the
      fact that the domains L1 and L2 of the alpha subunit, consisted of 119 and 118
      residues, contained the high and low affinity insulin binding sites,
      respectively, the cDNAs of L1 and L2 were obtained from a human placental cDNA
      library by PCR. The cDNAs of L1, L2 and L1-(Ala)(10)-L2(designed ten-alanine
      connected L1 and L2)were cloned, respectively, into an expression plasmid pET-3a,
      and E.coli BL21(DE3)transformants with such plasmids were successfully induced to
      express the goal proteins. The expression products were isolated and purified by
      the washing and solubilization of inclusion body, gel filtration chromatography
      and ion exchange chromatography. Each final product displayed a single band,
      corresponding the purity above 99%, in SDS-PAGE. These products have also been
      confirmed respectively as the L1, L2 and L1-(Ala)(10)-L2 by DNA sequencing, amino
      acid composition analysis and N-terminal amino acid sequencing.

PMID- 12058178
TI  - Conservation and Evolution of the "Core Apoptotic Engine" Lesson from the Genome
      Comparison of Drosophila.
AB  - Genome comparison is the main approach to deduce regulatory network from genome
      sequence. Apoptotic network is one kind of typical regulatory networks. EGL1,
      CED3, CED4, CED9 and their homologous proteins play essential roles in apoptosis
      of C.elegans and mammals, and were regarded as the components of the"core
      apoptotic engine". But in fruit fly, Drosophila melanogaster, this network is
      incomplete. A series of bioinformatic analyses found the lost chains of "core
      apoptotic engine" by discovering two homologues of BCL2/CED9 and one of EGL1 in
      fruit fly genome sequences. These findings proved that the "core apoptotic
      engine" is indeed widely conserved among multicellular organisms and the
      evolutionary complexity of this network of Drosophila is between that of
      C.elegans and mammals.

PMID- 12058179
TI  - Cloning of Metallotionein cDNAs and Its Gene in Shore Crab(Carcinus maenas).
AB  - Metallothioneins are cysteine-rich proteins which chelate metal ion(Zn, Cu, Hg
      and Cd)and regulate ion concentrations in animal body. Based on the published
      amino acid sequence of C.maenas metallothionein, completely degenerated PCR
      primers were designed and two different types of cDNA were amplified from gill
      tissue RNA of C.maenas using RT-PCR method. These cDNAs were cloned to pGEM T
      Easy Vector and the nucleotic acid sequences were determined. The results showed
      that one group of the cDNA sequence is exactly same as first 123 bases, as
      predicted from MTIb cDNA. Another group of cDNA was also amplified, which is
      truncated and different at the 3' end of cDNA. Based on the former cDNA sequence,
      specific primers were designed to amplify the full length MTIb cDNA coding
      region. The MTIb gene was also amplified and cloned into the pGEM Vectors. The
      gene sequence showed that MTIb gene contains two introns(575 bp and 602 bp),
      dividing the gene to three exons(22 bp, 77 bp and 78 bp).

PMID- 12058180
TI  - Regulation of Protein Kinase C in A-549 Cells by Phorbol Ester.
AB  - Protein kinase C, a family of serine-threonine protein kinases, mediates a
      variety of intracellular signaling events. Here, the regulatory effect of phorbol
      12-myristate 13-acetate(PMA)on the several PKC isozymes in the human lung
      carcinoma cells A-549 was studied. The expression of PKC-alpha PKC-betaII PKC
      gamma PKC-delta and PKC-epsilon in A-549 cells was examined. No detectable PKC
      zeta was observed. Short-term treatment of cells with PMA led to the
      translocation of these PKC isozymes, to different extent, from cytosol to cell
      membrane. Whereas, prolonged treatment of cells with PMA pronouncedly reduced the
      levels of PKC-alpha PKC-gamma PKC-delta and PKC-epsilon, but the intracellular
      level of PKC-betaII was not affected. Furthermore, PMA was observed to have
      differential effects on the down-regulation of PKC isozymes located in the
      cytosol and of those located in the membrane. Prolonged PMA treatment caused
      extensive decrease in the levels of cytosolic PKC-delta and PKC-gamma, and
      depleted cytosolic PKC-alpha and PKC-betaII. However, the amount levels of
      membrane PKC-alpha PKC-betaII PKC-gamma PKC-delta isozymes were not decreased. In
      contrast, PKC-epsilon in both cytosol and membrane fraction was obviously down
      regulated by prolonged PMA treatment. This study provided novel evidence on the
      PMA-mediated activation and down-regulation of different PKC isozymes, which
      might be helpful in deepening our understanding on the roles of PKC activation
      and the alterations of their intracellular levels in processes of chemical
      carcinogenesis.

PMID- 12058181
TI  - Cloning and Preliminary Characterization of Regulatory Domain of Mouse Nestin
      Gene.
AB  - Mouse nestin genomic DNA(23.3 kb)was obtained after genomic library screening.
      Sequence comparison of the cDNA and genomic DNA revealed three introns in this
      gene. The positions and length of these introns are conserved among rat and
      human. The effect of the second intron of mouse nestin gene on the expression of
      luciferase reporter gene was investigated in vitro. Transient transfection of the
      second intron and its series deletions of mouse nestin gene showed that the
      second intron of mouse nestin gene could enhance reporter gene expression and the
      activity was contributed by a fragment about 800 bp long of its 3' end.

PMID- 12058182
TI  - Purification and Characterization of a Platelet Agglutinating Inhibiting Protein
      (Agkisacutacin) from Agkistrodon acutus Venom.
AB  - A platelet agglutinating inhibiting protein (agkisacutacin) was isolated from the
      venom of Agkistrodon acutus by DEAE Sepharose Fast Flow and size exclusion
      chromatography. The purified product was a 29 kD protein composed of two
      disulfide bond-linked polypeptide chains of molecular weight of 14 kD, 15 kD,
      respectively. It completely inhibited ristocetin-induced platelet agglutination
      with an IC(50) value of 18.5 mg/L. It also inhibited thrombin-induced platelet
      aggregation with an IC(50) value of 1.22 g/L, but it did not affect the platelet
      aggregation induced by collagen and ADP. No fibrinolytic activity, phospholipase
      A(2) activity, anticoagulant activity, haemorrhagic activity or lethal activity
      were detected in agkisacutacin. Therefore this protein may offer considerable
      therapeutic potential in treatment of platelet-rich thrombosis.

PMID- 12058183
TI  - Molecular Cloning of a Gene Suppressed by Heat Shock and Its Expression
      Characteristics.
AB  - On the base of a cDNA fragment cloned from a human osteosarcoma cell line (HOS
      8603) which was taken as the model of heat shock by DDRT-PCR, the cDNA library
      was screened by the probe made from this fragment, and the colony containing full
      length cDNA of this cDNA fragment (HSSG-1) was identified. Sequencing data
      indicated that this cDNA consisted of 1 456 bp, coding for 276 amino acids.
      Computer aided homology analysis did not find the same sequence published. The
      result of RNA dot hybridization suggested that HSSG-1 was expressing in many
      kinds of organs and cells, and the down regulating of its expression level caused
      by heat shock was general. Therefore, this may be a gene that is suppressed by
      heat shock.

PMID- 12058184
TI  - Assay of Adenylyl Cyclase Activity by Ion-exchange High-performance Liquid
      Chromatography.
AB  - Adenylyl cyclase(AC)activity was determined by directly quantifying the product
      cAMP with ion-exchange HPLC. When AC reaction was terminated, the reaction
      mixture was kept at 0 degrees for 2 h to remove residual ATP utilizing the action
      of ATP-hydrolyzing enzymes existed in the crude AC preparation of membrane
      pellet. Papaverine was removed by the dichloromethane extraction, and cAMP was
      quantified by chromatography on a WAX-1 HPLC column with baseline-resolution. It
      was found that cAMP was linearly formed within 10 min of the reaction, and the
      amount of cAMP formed was proportional to the amount of enzyme. Mouse brain AC
      activity determined by this method was 42 nmol/min per gram of protein, similar
      to that obtained by the classical [(3)H] labeled ATP method. This ion-exchange
      HPLC was more rapid and convenient.

PMID- 12058185
TI  - Synthesis of Human Proinsulin C-peptide and Preparation of Specific Antibody to
      It.
AB  - A HPLC and CE pure human proinsulin C-peptide was synthesized by solid-phase
      method and TSK column purification. Its amino acid sequence and MS were
      consistent with theoretical values. In comparison with the formly reported
      chemical synthesis of C-peptide, this method has the advantage of simplicity and
      higher overall yield (41%). To improve the immunogenicity and specificity of
      oligopeptide antibody, the acrylyl-C-peptides were transformed into a polymer the
      product had a poly-propionyl-core matrix with C-peptide branches. This treatment
      gave a macromolecule with a M(r) about 25 kD. By using the polymer to immunize
      New Zealand rabbits for 30 days, specific antiserum was obtained with titer of
      2.5x10(4) (by ELISA), which did not cross react with BSA. Thus, the poly
      propionyl-peptide system provided a new approach for preparing synthetic peptide
      antibody and therefore is promising for the preparation of synthetic peptide
      based vaccine.

PMID- 12058186
TI  - Fused Expression of Anti-CEA Single-chain Antibody Gene with Core-streptavidin
      Gene in Insect Cells.
AB  - A fused construct formed by an anti-CEA single-chain antibody gene with a core
      streptavidin gene(ScFv-CS)was inserted into the donor plasmids pFastBacHTa and
      expressed in Tn-5B1-4 cells. SDS-PAGE analysis revealed that the molecular weight
      expressed product of ScFv-CS were 41 kD. Using horseradish peroxidase(HRP)labeled
      biotin as antibody product Western blot, one band of 41 kD only was detected. It
      was also shown by RIA that the expression product possessed the ability to bind
      to its specific antigen of CEA. These results showed that the fusion protein not
      only had the ability to bind CEA, but also could bind biotin specifically.

PMID- 12058187
TI  - A Strong Promoter Provided with the Gene Encoding Arginyl-tRNA Synthetase(argS)
      from Escherichia coli.
AB  - Previous studies showed that the gene argS encoding the arginyl-tRNA
      synthetase(ArgRS) from Escherichia coli(E.coli), was overexpressed 1 000 folds in
      the E.coli transformant TG1/pUC-argS, while the gene leuS, encoding the leucyl
      tRNA synthetase(LeuRS) from E.coli, was only overproduced 35-fold in the same
      case. To investigate why the expression of these two aminoacyl-tRNA synthetase
      genes is so different, a fused gene (termed parg-leuS) was constructed by
      replacement of the 5' flanking region of leuS to 5' flanking region of argS. In
      the E.coli transformant TG1/pUC-parg-leuS, the activity of LeuRS was only
      improved 8.5-fold, which was much lower than that of the transformant harboring
      the recombinant plasmid pUC18-leuS or pKK-leuS. However, by RNA dot hybridization
      the amount of mRNA produced in the transcription of parg-leuS was about 5 times
      than that of the wild type leuS, and was similar to that of pKK-leuS, suggesting
      that the promoter of argS is very strong. Analysis of the secondary structure
      around the initiation codon among three mRNAs showed that the secondary structure
      of the mRNA from parg-leuS was the strongest of the three mRNAs. From the
      results, it could be deduced that expression of the fused gene parg-leuS might be
      controlled at the translational level and the strong secondary structure of this
      mRNA may hinder translation initiation and result in a low translation
      efficiency.

PMID- 12058188
TI  - Effect of F209S Mutation of Escherichia coli AroG on Resistance to Phenylalanine
      Feedback Inhibition.
AB  - In Escherichia coli, 80% of the 3-deoxy-D-arabino-heptulosonate 7-phosphate(DAHP)
      synthase was encoded by aroG gene. The aroG gene was amplified by polymerase
      chain reaction(PCR) from strain K-12 and a mutant strain resistant to
      phenylalanine analogues. The PCR products were cloned and subject to DNA sequence
      analysis. A single base mutation of Tright curved arrow C was detected at
      nucleotide 625, which causes a substitution of Phe(209) by Ser in the gene
      product. The gene was expressed on pTrc99A in E.coli strain JM105. Under the
      induction of IPTG, distinct band with the expected molecule weight was detected
      on SDS-polyacrylamide gel electrophoresis and the specific activity of DAHP of
      the crude extract of the transformed cells increased by 1.8-fold. Enzyme activity
      inhibition analysis revealed the high resistance of mutant AroG to feedback
      inhibition by phenylalanine. JM105 cells harboring with mutant aroG gene showed
      were able to grow on medium containing higher concentration of analogues than
      that carrying normal aroG gene. Discussion was focused on the varieties of
      mutations contributing to desensitization of feedback inhibition.

PMID- 12058189
TI  - Nucleotide Sequence of a 4 730 Base Pairs Region of the Spodoptera litura
      Nucleopolyhedrovirus Genome.
AB  - A 4 730 bp region of the Spodoptera litura Nucleopolyhedrovirus genome EcoRI-E
      fragment was sequenced, in which the odv-e66 gene and other two ORFs, ORF 1086
      and the p34 gene, were found. The SpltNPV odv-e66 gene open reading frame was
      deduced to be 2 079 bp, encoding a protein of 692 amino acids. Unlike odv-e66
      genes of AcMNPV and LsNPV, only one transcriptional initiation conserved sequence
      ATAAG of the late gene was present upstream of the initial codon ATG of SpltNPV
      odv-e66 gene, and no poly(A) signal was detected at the 3' end of the gene. Four
      highly conserved regions homologous to those of LdNPV, LsNPV, AcMNPV, BmNPV,
      CfNPV and OpNPV were present in the amino acid sequence of SpltNPV ODV-E66
      protein, with the putative nuclear targeting signal(NTS) KKIWAEDGR in the fourth
      conserved region. The ORF upstream of the odv-e66 gene had the same direction of
      odv-e66 gene, but different reading frame. Besides the CAAT box, the early gene
      regulatory element ACGT and GC motifs and the transcriptional initiation
      conserved sequence TTAAG of the late gene were present at the 5' end of this ORF.
      A putative protein of 289 amino acid residues with Mr. about 34 kD was encoded by
      the ORF, so that it is named P34 protein. A leucine zipper and a leucine zipper
      like structure were found in the C- and N-termini of SpltNPV P34 protein
      respectively. The functions of those regulatory elements may be of great
      importance to SpltNPV genome. An 1 086 nt open reading frame (ORF) capable of
      encoding a 361 amino acids polypeptide was found at the 3' end of the odv-e66
      gene and in opposite direction. The ORF 1086 protein shares 44% amino acid
      sequence homology with AcMNPV ORF 109.

PMID- 12058190
TI  - Active cis-elements of PCNA Promoter in HeLa, HepG2, L-02 and MCF-7 Cell Lines.
AB  - Proliferating cell nuclear antigen (PCNA) is an auxiliary factor of DNA
      polymerase delta and epsilon and functions in DNA replication and repair. Using
      PCR methods, 17 sites within the human PCNA promoter from 60 to 538 were
      subjected to a 8 bp substitution mutagenesis. Wild type promoter and each mutated
      promoters were inserted into luciferase expression vector pGL2-Basic. These
      nonmutated and mutated PCNA promoters were assayed by transient transfection of
      the plasmids into HeLa, HepG2, L-02 and MCF-7 cell line, respectively. It was
      found that several sites were common cis acting elements and several sites were
      cell-specific cis acting elements. Data were further presented using in vitro
      transcription assay with HeLa and HepG2 nuclear extract.

PMID- 12058191
TI  - Mutations in the N-terminal Transcriptional Activation Region of Androgen
      Receptor in the Chinese.
AB  - Activation function (AF1) region of N-terminal domain of androgen receptor (AR)
      is necessary for the transcriptional activation function of AR. The sequences of
      AF1 in twenty normal chinese were amplified by PCR and determined by direct dsDNA
      cycle sequencing. Based on this, the mutations in AF1 of AR in patients with
      androgen insensitivity syndrome(AIS) or prostate cancer(PC) were screened by a
      combination of single strand conformation polymorphism(SSCP) analysis and direct
      dsDNA cycle sequencing. The sequences between normal chinese and other races were
      identical and one point mutation (C966A, Ser296Arg), which had not been reported
      so far, was identified in a patient with prostate cancer with poor
      differentiation. That suggests alteration of structure and function in AF1 of N
      terminal domain of AR might be relative with PC progression of some patients.

PMID- 12058192
TI  - Ligand Binding Domains of human Vascular Endothelial Growth Factor Receptor.
AB  - Four cDNA clones, encoding truncated Flt-1 mutants consisting of loop 2, 1-2, 2-3
      and 1-3, were amplified by PCR from human placenta cDNA library and the
      corresponding gene fragments were named Flt-1(2) Flt-1(1-2) Flt-1(2-3) and Flt
      1(1-3). In order to detect which part of the extracellular domain was involved in
      ligand binding, the interaction between Flt-1 mutants and hVEGF(165) was studied
      with yeast two-hybrid system. The data presented here suggest that both Flt-1(2
      3) and Flt-1(1-3) were able to bind hVEGF(165). Two recombinant expression
      plasmids, pPIC9K/Flt-1(1-3) and pPIC9K/Flt-1(2-3), were constructed and
      transformed into Pichia pastoris strain GS115, respectively. After 4 days of
      methanol induction, the amount of the expressed Flt-1s reached 60% of total
      proteins in supernatant by SDS-PAGE. Recombinant proteins were purified with CM
      Sepharose Fast Flow and Sephacryl S-100 chromatography. Biological activities
      analysis proved that 1-3 loop had slightly better biological activity than 2-3
      loop in VEGF(165) binding and in inhibition of HUVEC proliferation stimulated by
      hVEGF(165).

PMID- 12058193
TI  - Snake Muscle Creatine Kinase cDNA Molecular Cloning, Expression and Comparison
      with Evolutionarily Related Enzymes.
AB  - Snake muscle cDNA library was constructed, and an allelic cDNA coding for M-type
      creatine kinase was cloned through screening library with antibody. A complete
      open reading frame(1 140 bp) codes for 380 amino acids which shows high homology
      with known creatine kinase isoenzyme. After cloning into expression vector
      pET11a, the snake muscle creatine kinase(SM-CK) was over-expressed in Escherchia
      coli. Kinetical studies showed that purified recombinant SM-CK exhibited behavior
      similar to the tissue form. Evolutionary tree of M-type creatine kinase was then
      constructed, and it was determined that this allelic cDNA of snake muscle
      creatine kinase belonged to M-type situated between in mammals and birds. These
      findings, along with the following SM-CK gene regulation studies, may shed light
      on the role of creatine kinase in energy generation during hibernation as well as
      the molecular basis of myogenesis during ontogeny.

PMID- 12058194
TI  - Identification of the Peptides that Bind to Tyrosine Kinase Receptor EphB2 by
      Phage Display.
AB  - The gene encoding the Ig-like domain of tyrosine protein kinase receptor EphB2
      was cloned into the expressing vector pET28a. Under induction with IPTG, the
      positive strain expressed the fusion protein with a hexahistidine tail on the N
      terminal. The protein was purified under denaturing conditions using metal
      chelate chromatography. The purity was up to 94%. The purified-protein-coated
      ELISA plate was used as target to screen recombinant phages able to bind onto it,
      and after three rounds of affinity screening, 19 phages that could bind
      specifically with EphB2 were isolated from a random phage-displayed seven-peptide
      library. The peptide sequences of the positive phage clones were analyzed.

PMID- 12058195
TI  - Possible Role of B8Gly in Insulin Structural Motif.
AB  - In the insulin structural motif n1-Cys-Gly-X10-Cys-n2-Cys-Cys-X3-Cys-X8-Cys-n3,
      there are seven absolutely conserved amino acid residues, and the only Gly is at
      position B8. When B8Gly was substituted with Ala by means of site-directed
      mutagenesis, a mutant insulin, [B8Ala]human insulin was obtained. The receptor
      binding capacity and in vivo biological activity of the [B8Ala]human insulin were
      about 2.5% and 10% of native porcine insulin, respectively. The far-UV circular
      dichroism (CD) spectra of [B8Ala]human insulin and human insulin showed that the
      relative content of alpha-helix in the mutant somewhat decreased. The results
      indicate that the B8Gly in the insulin structural motif is unreplaceble.

PMID- 12058196
TI  - Cloning, Expression and Biological Activity of VEGI(151), a Novel Vascular
      Endothelial Cell Growth Inhibitor.
AB  - VEGI(vascular endothelial cell growth inhibitor) is a novel cytokine which
      belongs to the TNF super-family. In this study, the VEGI gene from ECV304 cells
      was cloned. A truncated form of VEGI, where 23 amino acids from N-terminal were
      deleted and named VEGI(151), was expressed in E.coli with 25.5% of expression
      rate. The purity of VEGI(151) reached 92.5% after purification. VEGI(151) showed
      significant inhibitory effect on endothelial cells. IC(50) of VEGI151 was 10 mg/L
      at 24 h. At the concentration of 0.613 mg/L, VEGI(151) induced apoptosis of
      endothelial cells within 36 h. However, neither stimulatory effect nor inhibitory
      effect of VEGI(151) was detected on tumor cells(A549 HepG2 Hela)cultured in
      vitro. These results suggest that endothelial cells was the main target cells of
      VEGI(151). Our findings indicate that VEGI(151) is a potential therapeutic drug
      on angiogenic disease and cancer.

PMID- 12058197
TI  - Effects of Divalent Cations and Disulfide Bond Reducing Agents on Specific
      Binding of Growth Hormone to Liver Membrane Receptors from Snakehead Fish
      (Ophiocephalus argus, Cantor).
AB  - Divalent cations, Ca(2 ), Mg(2 ) and Mn(2 ) enhance the binding of bream growth
      hormone (brGH) to snakehead fish liver membrane, and their optimum concentration
      was found to be 8 12 mmol/L, at which Ca(2 ), Mg(2 ) and Mn(2 ) could increase,
      respectively, the specific binding to 230%, 180%, and 200%, compared with the
      binding in the absence of ions. The Eadie-Scatchard plot was used for the dynamic
      analysis of the Ca(2 ) binding site. A low affinity Ca(2 ) binding site was found
      in the GH-receptor complex with K(m)=0.384 mmol/L, and the affinity constant
      (K(a)) was increased from 1.045x10(9) L.mol(-1) to 1.295x10(9) L.mol(-1) by the
      addition of 10 mmol/L CaCl(2). The effects of disulfide bond reducing agents, DTT
      and ME, on (125)I-brGH binding to growth hormone receptor (GHR) on snakehead fish
      liver memebrane were also analyzed. The addition of 0.1 20 mmol/L DTT or 0.01% 1%
      ME to the radioreceptor assay system caused a significant dose dependent increase
      in the specific binding for (125)I-brGH. In the presence of 0.8 mmol/L DTT or
      0.08% ME, the specific binding of (125)I-brGH was increased from 10.2% to 15.5%
      and 13.2% respectively, and the affinity constant was also increased from
      1.265x10(9) L.mol(-1) to 2.185x10(9) L.mol(-1) and 1.625x10(9) L.mol(-1),
      respectively but no changes in the binding capacity were observed. Further
      studies showed that the effects of reductants on the specific binding of brGH
      were due in part to the ligand itself and in part to GHR. In addition, it was
      observed that one of the three disulfide bonds of brGH could be reduced by 0.8
      mmol/L DTT.

PMID- 12058198
TI  - Purification and Partial Characterization of S-trichokirin, A New Small Ribosome
      inactivating Protein, from Seeds of Trichosanthes kirilowii.
AB  - A new small ribosome-inactivating protein named S-trichokirin from the seeds of
      Trichosanthes kirilowii was purified by ammonia sulfate precipitation, CM-52 ion
      exchange chromatography, Sephacryl S-100 gel filtration and FPLC Mono S ion
      exchange chromatography. S-trichokirin has molecular weight about 8 kD, as
      determined by 15% SDS-PAGE and 15% Tris-Tricine PAGE. It was proved to be a
      strong basic protein with pI about pH 9.5 by 13.5% acidic PAGE. The reaction
      mechanism of S-trichokirin is the same as that of trichosanthin, which is an RNA
      N-glycosidase. It had a strong inhibitory effect on protein biosynthesis in
      rabbit reticulocyte lysate with IC(50) of 1.15x10(-10) mol/L. S-trichokirin may
      be used as a new efficient moiety of immunotoxin.

PMID- 12058199
TI  - Cloning and Optimized Expression of Human Angiogenin in E.coli.
AB  - Angiogenin(ANG) is an important factor of angiogenesis during different stage of
      tumor development and exists widely in various tumors. To study the biological
      funcption and find the antagonistic drugs of angiogenin, the angiogenin was
      allowed to be expressed by E.coli. By the aid of computer, the sequence around
      the start codon of angiogenin gene was modified according to local secondary
      structure. The modified human ang gene was amplified by reverse-transcription
      polymerase chain reaction from the human lung cancer cell line A549, and inserted
      into the prokaryotic expression vector pLDH99. After screening, high expression
      recombinants were obtained, and the expression level of the hANG was about 30% of
      total bacteria protein by SDS-PAGE. Biological assays indicated that the rhANG
      could induce new blood vessel formation in CAM in vitro. Our data showed that the
      recombinant hANG was active and the optimized expression of ang gene was
      practicable.

PMID- 12058200
TI  - Purification and Characterization of Recombinant Hepatitis B Virus Surface
      Antigen SS1 Expressed in Pichia pastoris.
AB  - The purification of recombinant hepatitis B surface antigen, SS1 protein,
      expressed in Pichia pastoris, and the investigation of its physiochemical
      characters and immunogenicity were described here. Employing McAb immunoaffinity
      chromatography, this protein was purified to purity of 95%. The results of ELISA
      and Western blotting showed good antigenicity of this purified SS1 protein. CsCl
      gradient centrifugation and electron microscopy assay proved that this purified
      protein could be assembled into particles similar to the HBV subviral particles.
      Strong antibody responses against both the HBs and PreS1 epitopes were induced in
      BALB/c mice immunized with this purified protein. The simultaneous injection of a
      CpG adjuvant induced a Th1-like immune response against both the HBs and PreS1
      epitopes.

PMID- 12058201
TI  - Cloning and Identification of Genes Related with Morphogenesis of Candida
      albicans.
AB  - A Candida albicans cDNA library was constructed and screened by differential
      hybridization. In hybridization using probes derived from population of yeast
      cells or hyphae, 67 recombinant phages exhibited more intense signal with the
      probe derived from hyphae than with the probe from yeast cells. One phage behaved
      vice versa. Physical map analysis and nucleotide sequence analysis suggested that
      cDNA of the CX1, a clone specific for yeast form, coded for cytochrome P450 L1A1
      (Lanosterol 14alpha-demethylase). Its specific expression pattern was confirmed
      by Northern analysis. Inhibition of serum on the expression of CX1 cDNA was
      observed. CX2 cDNA was one of those giving intensive signal with hyphae probes.
      The cDNA sequence contained a tandem repeat sequence, which was also found in
      ALS1, another Candida albicans gene identified, whose expression was related with
      morphogenesis. Northern analysis proved that it was expressed intensively with
      hyphae probes, however the expression could not be detected in those strongly
      hybridized to yeast cell probes. The locations of both cDNA on chromosome were
      analyzed.

PMID- 12058202
TI  - Using Kl LAC4 as a Reporter Gene in Candida albicans.
AB  - The lacZ gene which codes for beta-galactosidase from E.coli does not work in
      Candida albicans. In this work a reporter system with Kl LAC4 gene was
      contructed, coding for beta-galactosidase from Kluyveromyces lactis. Kl LAC4 gene
      was fused to the promoter of ADH1 of Candida albicans with the terminator
      sequence of ADH1 at the tail. The constructed plasmid, named pYPB1-LAC4, was used
      to transform Candida albicans. beta-galactosidase activity was measured by plate
      assay, when cultured on solid medium, and by photometric assay, when cultured in
      liquid medium. The results suggest that LAC4 of Kluyveromyces lactis can serve as
      a reporter gene in Candida albicans.

PMID- 12058203
TI  - Scanning Tunneling Microscopy of the Ultrastructure of Cotton Fiber.
AB  - The ultrastructure of the cotton fiber in Lumian No.11 was investigated with
      scanning tunneling microscope (STM), and the results were compared with that by
      scanning electron mincrocope(SEM). With SEM, fibrils could be seen, it was
      difficult, however, to further observe the fine structures in fibrils. Otherwise,
      with STM, fibrils could be seen clearly, and by making scan areas smaller, it
      could be observed that the fibrils were composed of microfibrils, and the
      microfibrils were composed of elementary fibrils, which were the smallest
      structural units of the fibril, which were arranged in parallel.

PMID- 12058204
TI  - Cloning and Secretion Expression of Heat-shock Protein 70 Gene of Helicobacter
      pylori.
AB  - Heat-shock protein 70 gene (hsp70)was obtained by PCR method from Helicobacter
      pylori chromosomal DNA. Sequencing analysis exhibited that the hsp70 gene
      isolated from Hp Y(2) was highly homologous with the gene encoded in Helicobacter
      pylori 26695 and J99, which had been sequenced for complete genome. The hsp70
      gene was recombined in vitro with fusion secretion expression vector pMAL-p2 and
      was transformed into E.coli cells. The E.coli strains, containing hsp70
      recombinant plasmid, expressed a 113 kD fusion protein which accounted for 19.4%
      of the total bacterial periplasm protein after the induction with IPTG for 5 h at
      30 degrees. The expressed fusion protein could react specifically with anti
      Helicobacter pylori rabbit IgG, as proved by Western blot method.

PMID- 12058205
TI  - Mechanosensitive Channel Currents Recorded in Rat Brain Microvascular Endothelial
      Cells with Whole-cell Mode.
AB  - Using the whole-cell patch-clamp technique, delayed outward currents were
      recorded in rat brain microvascular endothelial cells(RBMECs), which were nearly
      completely inhibited by extracellular TEA-Cl at a concentration of 20 mmol/L.
      Whole-cell currents were elicited by 2 100 ms depolarizing voltage pulses applied
      every 7 s between -100 mV to +90 mV, with 10 mV increment, from a holding
      potential of -100 mV. The currents were similar with delayed rectified K(+)
      currents (IKv)which were inhibited in a concentration-dependent manner by both
      application of TEA-Cl, with an IC(50) approximately 2.0 mmol/L. In the presence
      of mechanical force, outward currents were increased in amplitude as compared
      with controls. These mechanical force-induced currents were also defined as IKv,
      which were different from previous described mechanosensitive currents induced by
      mechanical force with characteristic of inward rectifier.

PMID- 12058206
TI  - Arginine Vasopressin(4-8) Mobilizes Intracellular Calcium in C6 Glioma Cells.
AB  - To understand the mechanism of neurotrophic action of neuropeptide ZNC(C)PR,
      which could affect growth of C6 cells, fluorescent dye Fluo-3 and confocal laser
      scanning microscope were used to assay the intracellular calcium in C6 glioma
      cells. It was found that ZNC(C)PR and it's analogue NLPR could mobilize
      intracellular calcium in a dose-dependent manner. The ZNC(C)PR antagnist,
      ZDC(C)PR, could inhibit the process, and the extracellular calcium did not
      influence it.

PMID- 12058207
TI  - Cloning and Sequence Analysis of the Chitinase Gene of Spodoptera litura Nuclear
      Polyhedrosis Virus.
AB  - Using AcMNPV chiA-containing fragment as a probe, the chitinase gene of
      Spodoptera litura nuclear polyhedrosis virus (SpltNPV) was localized in two
      contiguous fragments, XbaI 5.1 kb and 2.1 kb, and the intact SpltNPV chiA gene
      was obtained by cloning and sequencing those two fragments. The complete open
      reading frame of the gene was 1 695 nucleotide long, encoding a putative protein
      of 564 amino acids with molecular weight of 62.9 kD. Sequence analysis further
      revealed that the 5' noncoding region had a baculovirus late promoter motif TAAG.
      A polyadenylation signal, AATAAA, was located dowmnstream of the translation stop
      codon. A putative signal peptide was present at the N-terminus of the protein.
      This gene shares 57% homology with AcMNPV chitinase gene.

PMID- 12058209
TI  - Cloning and Expression of Actin Gene of Schistosoma japonicum Chinese Strain.
AB  - A 1 131 bp cDNA fragment was amplified by RT-PCR from adult Schistosoma
      japonicum(Chinese strain) mRNA with primers designed according to published
      SmAct2 encoding Schistosoma mansoni actin. Sequence analysis indicated that this
      fragment, with 92% homology to SmAct2, was a complete open reading fragment (ORF)
      of actin gene of Schistosoma japonicum (Chinese strain). This gene was cloned
      into the expression vector pET28a( ) and subsequently expressed in Escerichia
      coli. SDS-PAGE revealed that the molecular weight of this expressed product was
      47 kD. Western blotting showed that the recombinant protein had good reactivity
      with the rabbit serum immunized with Sj worm antigen, indicating that this gene
      encode actin of Schistosoma japonicum(Chinese strain).

PMID- 12058208
TI  - Identification of Glucose-responsive and Insulin-responsive Elements in Promoter
      of Mouse ob Gene.
AB  - Glucose and insulin stimulate leptin gene expression in vitro and in vivo. To
      identify cis-elements that are responsible for the glucose and insulin effects,
      mouse 3T3-L1 adipocytes were transiently transfected with reporter constructs
      with serial deletions in mouse ob gene promoter. The cis-elements were identified
      with Gel mobility shift assays (GMSA), DNase I footprint assays and PCR mediated
      site-directed mutation assays. Transient transfections detected a negative cis
      acting element, a glucose-responsive element (GLRE), and an insulin-responsive
      element (IRE) in the region from -1 719 bp to -1 452 bp of mouse ob gene. This
      region does not contain any known GLRE or IRE. GMSA identified a DNA binding
      protein which specifically binds a native probe prepared from mouse ob gene
      promoter (-1 719 bp/-1 452 bp), and the binding was repressed by glucose or
      insulin. DNase I footprint assays and PCR mediated site-directed mutations assays
      identified that the binding motif AGCAAAA, spanning -1 698 bp to -1 692 bp of the
      mouse ob gene promoter, was responsible for the effects of glucose and insulin on
      ob gene expression. These studies suggest that a negative cis-acting element is
      located between -1 719 bp and -1 452 bp of the mouse ob gene promoter, and
      glucose and insulin simulate mouse ob gene expression by repressing the binding
      of a transcription factor to this element. This element, AGCAAAA, spanning -1 698
      bp to -1 692 bp is a novel GLRE and IRE.

PMID- 12058210
TI  - Intervention in the lacrimal drainage system.

PMID- 12058211
TI  - Wedged hepatic venography for targeting the portal vein during TIPS: comparison
      of carbon dioxide and iodinated contrast agents.
AB  - PURPOSE: Carbon dioxide (CO2) can traverse the hepatic sinusoids better than
      iodinated contrast medium and has been used by many interventionalists for wedged
      hepatic venography during transjugular intrahepatic portosystemic shunt (TIPS)
      procedures. Our study was designed to compare the extent of the portal vein
      opacification using either CO2 or iodinated contrast medium. METHODS: Wedged
      hepatic venography for portal vein opacification during TIPS was performed using
      hand injection through a 6.5 Fr diagnostic catheter. Portograms of 36 patients
      performed with 10 ml of iodinated contrast medium were retrospectively compared
      with portograms of 45 patients performed with 30-40 ml of CO2. Opacification of
      the right portal vein branch including the portal vein bifurcation was defined as
      a successful study. RESULTS: Using CO2 the right portal vein branch and the
      portal vein bifurcation were opacified in 87% of patients (39 of 45); only a part
      of the right portal vein branch was opacified in 6% of patients and no
      opacification of any portal vein branch was seen in 7% of patients. Using
      iodinated contrast medium, there was opacification of the portal vein bifurcation
      in 25% of patients (9 of 36), of a part of the portal vein branch in 36% and no
      opacification of any branch in 39%. There was one case of hepatic laceration from
      CO2 wedged venography which was treated with microcoil embolization. CONCLUSIONS:
      Using CO2 as a contrast medium, opacification of the portal vein bifurcation by
      wedged hepatic venography was seen in 87% of patients, in comparison with only
      25% when iodinated contrast medium was used (p < 0.001). CO2 is superior to
      iodinated contrast medium for wedged hepatic venography during TIPS.

PMID- 12058212
TI  - Obstructive jaundice in hepatocellular carcinoma: response after percutaneous
      transhepatic biliary drainage and prognostic factors.
AB  - PURPOSE: To evaluate the therapeutic effect of percutaneous transhepatic biliary
      drainage (PTBD) in patients with obstructive jaundice caused by biliary
      involvement of hepatocellular carcinomas (HCC) and to determine the prognostic
      factors. METHODS: We retrospectively analyzed the data of 22 consecutive patients
      (M:F = 20:2, mean age 52.8 years). Inclusion criteria were the patient having
      obstructive jaundice caused by HCC that invaded the bile ducts and having at
      least 4 weeks of follow-up data after the PTBD. We defined "good response" and
      "poor response" as whether the level of total bilirubin decreased more than 50%
      in 4 weeks or not. Total bilirubin level (T-bil), Child-Pugh score and the
      location of biliary obstruction for the two groups were compared. In addition,
      the interval between clinical onset of jaundice and PTBD, the degree of
      parenchymal atrophy and the size of the primary tumor were compared. RESULTS: Of
      the 22 patients, 13 (59.1%) showed good response. T-bil was significantly lower
      in the good response group than in the poor (14.2 +/- 6 mg/dl vs 25.9 +/- 13.8
      mg/dl, p =.017). In the five patients with T-bil <10 mg/dl, four (80%) showed
      good response, while in nine patients with T-bil > 20 mg/dl, only three (33%)
      showed good response. Although statistically not significant, patients with Child
      score <10 showed better results [good response rate of 66.7% (12/18)] than
      patients with Child score > or = 10 [good response rate of 25% (1/4)].
      Involvement of secondary confluence of the bile duct also served as a poor
      prognostic factor (p = 0.235). The interval between clinical onset of jaundice
      and PTBD, the presence of parenchymal atrophy and the size of the tumor did not
      show significant effect. CONCLUSION: Early and effective biliary drainage might
      be necessary in this group of patients with limited hepatic function.

PMID- 12058213
TI  - Efficacy of nonsurgical treatments for hepatocellular carcinoma in the caudate
      lobe.
AB  - PURPOSE: To evaluate the efficacy of nonsurgical treatments for caudate
      hepatocellular carcinoma (HCC). METHODS: Between January 1994 and February 2001,
      25 patients were treated for HCCs with percutaneous ethanol injection (PEI),
      and/or transcatheter arterial embolization (TAE). PEI was performed for 19
      caudate HCCs, combined treatment with PEI and TAE for 4 nodules, and TAE for 2
      nodules. RESULTS: During follow-up periods ranging from 3 to 60 months (mean 21.3
      months), 18 patients had no local recurrence. Local recurrence was seen in 7
      patients, and recurrence in the other segments of the liver in 15 patients.
      Thirteen patients were alive, ranging from 6 to 60 months, and 12 patients died
      of multiple HCCs, hepatic failure, or rupture of esophageal varix. The 1-, 2-, 3
      , and 5-year survival rates of the 25 patients were 70.6%, 60.2%, 48.1%, and
      16.0%, respectively. CONCLUSION: PEI, PEI and TAE, or TAE would be an effective
      alternative treatment for HCC in the caudate lobe.

PMID- 12058214
TI  - Efficacy of permanent and retrievable vena cava filters: experimental studies and
      evaluation of a new device.
AB  - PURPOSE: To evaluate the efficacy of vena cava filters and to compare them with
      the new TrapEase filter. METHODS: Thrombus capture rates of 10 permanent and
      retrievable vena cava filters were tested in vitro in vertical and horizontal
      positions with thrombus diameters of 3 and 5 mm (length 30 mm) and tube diameters
      of 21 and 28 mm. Testing included the new TrapEase filter. Results compared
      statistically using Fisher's exact test (capture rates) and the Kruskal-Wallis
      test (construction). RESULTS: Best-ranked filters were the Bird's Nest, the
      TrapEase and the Simon Nitinol filters. The Tempofilter, the Greenfield and the
      Keeper filter performed worst. Thrombus capture rates were significantly higher
      in the vertical position and also higher for large thrombi and in the small cava
      diameter. Conical filters performed worse than filters with two or more
      filtration levels. CONCLUSION: Filters with two or more filtration levels show
      the highest filtration efficiency in vitro and can be recommended, especially for
      the critically ill who will probably not tolerate even small emboli. The TrapEase
      filter is a promising device and should be evaluated clinically.

PMID- 12058216
TI  - Lethal hemorrhage caused by aortoenteric fistula following endovascular stent
      implantation.
AB  - A 55-year-old women developed an aortointestinal fistula between the bifurcation
      of the aorta and the distal ileum following implantation of multiple endovascular
      stents into both common iliac arteries for treatment of aortoiliac occlusive
      disease. Ten months before the acute onset of the gastrointestinal hemorrhage two
      balloon-expandable steel stents had been implanted into both common iliac
      arteries. Due to restenosis and recurrent intermittent claudication, three
      balloon-expandable covered stents were implanted 4 months later on
      reintervention. The patient presented with abdominal pain and melena, and fell
      into hemorrhagic shock with signs of upper gastrointestinal bleeding. After
      transfer to our hospital, she again developed hemorrhagic shock with massive
      upper and lower gastrointestinal bleeding and died during emergency laparotomy.
      The development of aortoenteric fistulas following endovascular surgery/stent
      implantation is very rare and has to be considered in cases of acute
      gastrointestinal hemorrhage.

PMID- 12058215
TI  - A new nitinol monofilament stent: early experience with use for transjugular
      intrahepatic portosystemic shunts.
AB  - The purpose of this study was to investigate the suitability of a new nitinol
      monofilament stent (Niti-S) for transjugular intrahepatic portosystemic shunt
      (TIPS) creation. TIPS was performed with a Niti-S stent in 22 patients for
      variceal bleeding (n = 20) or intractable ascites (n = 2). The efficacy,
      complication, and patency rates during the follow-up period (up to 27 months,
      mean 13.9 months) were evaluated. TIPS was successfully performed in all
      patients. The mean portosystemic pressure gradient decreased from 23.8 +/- 7.2
      mmHg to 10.2 +/- 3.1 mmHg. No mortality or significant morbidity was encountered
      at 1 month. Variceal bleeding and/or ascites were controlled in all patients.
      Primary patency rates were 77.3% at 6 months and 71.8% at 1 year. Secondary
      patency rates were 95.4% up to 26 months. TIPS with the Niti-S stent produced
      short-term technical and clinical results comparable to the other commercially
      available stents. A prospective randomized comparison study is indicated.

PMID- 12058217
TI  - Percutaneous and endovascular embolization of ruptured hepatic artery aneurysm.
AB  - A 72-year-old woman presented with an intraperitoneal hemorrhage from a ruptured
      intrahepatic artery aneurysm, with an associated pseudoaneurysm developing a high
      flow arteriovenous fistula. Persistent coagulopathy and a median arcuate ligament
      stenosis of the celiac axis further complicated endovascular management. Aneurysm
      thrombosis required percutaneous embolization with coils, a removable core
      guidewire and polyvinyl alcohol particles.

PMID- 12058218
TI  - Endovascular treatment of aberrant systemic arterial supply to normal basilar
      segments of the right lower lobe: case report and review of the literature.
AB  - We report the case of a 17-year-old man with acute chest pain due to a partial
      thrombosis of a pseudosequestration. Unlike a true sequestration, there was a
      normal bronchial distribution and the involved lung parenchyma was normal on CT
      scan. A therapeutic transarterial embolization of the aberrant systemic artery
      from the proximal abdominal aorta was performed successfully. The patient did not
      suffer from further chest pain during the follow-up of 12 months. A contrast
      enhanced CT scan 4 months later demonstrated complete occlusion of the embolized
      aberrant artery. Our case represents an alternative treatment to surgery for this
      rare abnormality.

PMID- 12058219
TI  - Limitations of endovascular treatment with stent-grafts for active mycotic
      thoracic aortic aneurysm.
AB  - An 81-year-old woman with ruptured mycotic thoracic aortic aneurysm was treated
      with endovascular placement of stent-grafts fabricated from expanded
      polytetrafluoroethylene and Z-stents. Although exclusion of the aneurysm was
      achieved at the end of the procedure, a type I endoleak developed on the
      following day. Despite emergent surgical resection of the aneurysm and extra
      anatomical reconstruction, the patient died 2 days later. Stent-graft repair may
      not be a suitable method for the treatment of ruptured mycotic aneurysm in the
      presence of active infection.

PMID- 12058220
TI  - Hepatic encephalopathy secondary to intrahepatic portosystemic venous shunt:
      balloon-occluded retrograde transvenous embolization with n-butyl cyanoacrylate
      and microcoils.
AB  - We report a 70-year-old woman with hepatic encephalopathy due to an intrahepatic
      portosystemic venous shunt that was successfully occluded by percutaneous
      transcatheter embolization with n-butyl cyanoacrylate and microcoils.

PMID- 12058221
TI  - Percutaneous removal of encapsulated foreign body from the peritoneum.
AB  - A novel method of removal of a walled off foreign body in the peritoneum using
      the percutaneous nephroscope is presented.

PMID- 12058222
TI  - Transjugular intrahepatic portosystemic shunt in a child with Budd-Chiari
      syndrome: technical modification and extended followup.
AB  - An 8-year-old girl with Budd-Chiari syndrome presented with upper
      gastrointestinal hemorrhage and ascites. TIPS to decompress the portal
      hypertension was performed by puncturing the portal vein directly from the
      inferior vena cava. The shunt remains patent after 3 years without requiring
      secondary intervention.

PMID- 12058223
TI  - Re: type a aortic dissection with expanding abdominal aortic aneurysm: treatment
      with endovascular stent-grafting.

PMID- 12058224
TI  - Re: congenital arteriovenous malformation in the neck successfully treated by
      direct puncture and embolization with n-butyl cyanoacrylate and a microcoil.

PMID- 12058230
TI  - The use of radioimmunoconjugates in stem cell transplantation.
AB  - Radiolabeled monoclonal antibodies have been used with encouraging results in
      conjunction with stem cell transplantation for patients with hematologic
      malignancies targeting a variety of surface antigens including CD33, CD45 and
      CD66 for leukemias, CD20 and CD22 for non-Hodgkin's lymphomas, and ferritin for
      Hodgkin's disease. The results obtained targeting epithelial antigens on solid
      tumors, however, have generally been less encouraging, primarily due to the
      relative insensitivity of these malignancies to ionizing radiation. In this
      report we review clinical studies that have incorporated myeloablative doses of
      targeted radiation using radiolabeled antibodies in conjunction with stem cell
      transplant regimens.

PMID- 12058231
TI  - Allogeneic related donor hematopoietic stem cell transplantation for treatment of
      chronic lymphocytic leukemia.
AB  - Between 1980 and 1999, 25 patients with chronic lymphocytic leukemia (CLL)
      received related donor hematopoietic stem cell transplants. Median patient age
      was 46.6 years. Preparative regimens included busulfan (BU) plus cyclophosphamide
      (CY), CY plus TBI, and etoposide, CY plus TBI. Twenty-one donors were HLA
      identical siblings, one was a DR mismatched sibling, and three were identical
      twins. Bone marrow was the source of hematopoietic stem cells in 22 cases and G
      CSF stimulated peripheral blood in three cases. Most patients received
      methotrexate and cyclosporine for GVHD prophylaxis. Fourteen patients developed
      grades 2-4 acute GVHD and 10 developed clinical extensive chronic GVHD. Late
      clearance of CLL cells was associated with the development of chronic GVHD in one
      patient. Two patients had recurrent CLL. Nonrelapse mortality at day 100 was 57%
      for the seven patients conditioned with BU/CY and 17% for the 18 patients
      conditioned with TBI-containing regimens. Actuarial survival at 5 years for the
      25 patients is 32%. All patients who received BU/CY died within 3 years of
      transplant. For the 14 patients transplanted since 1992 and who received TBI,
      actuarial 5-year survival is 56%. The maximum response of CLL to hematopoietic
      cell transplantation may be delayed, but long-term disease-free survival can be
      achieved.

PMID- 12058232
TI  - Factors influencing hematopoietic recovery after autologous blood stem cell
      transplantation in patients with acute myeloblastic leukemia and with non-myeloid
      malignancies.
AB  - Factors influencing hematopoietic recovery (HR) after autologous blood stem cell
      transplantation (ABSCT) were analyzed in 73 patients with various non-myeloid
      malignancies (NMM), and in 58 patients with acute myeloblastic leukemia (AML).
      Peripheral blood stem cells were collected following mobilization with
      chemotherapy, granulocyte colony-stimulating factor (G-CSF), or chemotherapy plus
      G-CSF. The conditioning regimen used consisted of either chemotherapy alone (112
      cases) or chemotherapy plus total body irradiation (19 cases). The median number
      of colony-forming units granulocyte-macrophage (CFU-GM) was similar in both
      groups of patients, with the median number of CD34(+) cells infused being higher
      in the AML group (5.4 vs 4 x 10(6)/kg; P = 0.03). Median time neutrophils >0.5 x
      10(9)/l was 13 days in both groups, and median time to a platelet count >20 x
      10(9)/l was longer in AML patients (14 vs 12 days; P = 0.01). In multivariate
      analysis, the only factors affecting neutrophil recovery in the NMM group were
      the CD34+ cell number (continuous model) and the CFU-GM dose (categorized model)
      infused, whereas for platelet recovery, previous chemotherapy also remained
      significant. In the AML group, the only factors significantly affecting the speed
      of neutrophil recovery were dose of CD34+ cells administered and the patient's
      age. As for platelet recovery, only the progenitor dose administered remained
      significant. In the NMM group, the most discriminating cut-off values for a rapid
      neutrophil and platelet recovery were 1.5 x 10(6) and 2.5 x 10(6) CD34+ cells/kg,
      respectively, and for AML patients these figures were 1.5 x 10(6) and 4 x 10(6)
      CD34+ cells/kg, respectively. Our results confirm the slower HR after ABSCT in
      AML, and highlight the importance of progenitor cell dose in accelerating HR
      after ABSCT.

PMID- 12058233
TI  - Front-line high-dose therapy with autologous stem cell transplantation for high
      risk Hodgkin's disease: comparison with combined-modality therapy.
AB  - This retrospective study compares high-dose therapy (HDT) with autologous stem
      cell transplantation and combined-modality treatment (CT) as a first-line therapy
      for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or
      a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at
      diagnosis, and an incomplete response after the first-line chemotherapy. Data on
      42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality
      treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81
      and H90) was analyzed. Both groups were comparable except for pulmonary disease
      in excess in the grafted group (P = 0.01). Among GP, 95% were in complete
      response at the end of first-line treatment and 77% among CTP. Median follow-up
      was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181
      months) for CTP. The 5-year freedom from progression (FFP) and event-free
      survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81%
      vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not
      differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were
      obtained for the groups with a response > or =50% after initial chemotherapy: 91%
      vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P
      = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003;
      72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows
      a better control of the disease with HDT.

PMID- 12058234
TI  - Bone marrow transplantation for paediatric AML in first remission: a systematic
      review and meta-analysis.
AB  - For children with AML in CR1, the major consolidation therapies are BMT, ABMT and
      intensive chemotherapy. The relative effectiveness of these strategies is still
      debated. We conducted a systematic review and meta-analysis of trials to
      determine the effectiveness of BMT and ABMT in CR1 in paediatric AML. Eligible
      studies enrolled patients <21 years from 1985 to 2000 with AML in CR1. Two groups
      of studies were identified: (1) Those comparing the outcome of patients with and
      without a histocompatible family donor; and (2) Randomised controlled trials
      (RCT) comparing ABMT with non-myeloablative chemotherapy. The relative risk
      statistic was calculated for outcomes of interest in each trial. If there was no
      excessive heterogeneity between trials the results were pooled, and an overall
      relative risk and risk difference for treatment effect across trials were
      calculated. Results of the analysis showed that allocation to BMT reduced risk of
      relapse and improved disease-free and overall survival. For ABMT, heterogeneity
      of effect between RCTs prevented pooling of results. In conclusion, BMT from a
      histocompatible family donor improves patient outcome. Data are insufficient to
      determine whether this is true for all subgroups of AML, and whether ABMT is
      superior to non-myeloablative chemotherapy. An individual patient data meta
      analysis is required to further evaluate the available data.

PMID- 12058235
TI  - Does donor-recipient ABO incompatibility protect against relapse after allogeneic
      bone marrow transplantation in first remission acute myeloid leukemia?
AB  - It is not known if donor-recipient ABO blood group incompatibility contributes to
      graft-versus-leukemia after allogeneic BMT. One hundred and nineteen patients
      with acute myeloid leukemia in first remission underwent non-T cell-depleted
      marrow allografts from HLA-identical siblings after TBI and cyclophosphamide (n =
      72) or melphalan (n = 47). GVHD prophylaxis comprised cyclosporine alone or
      cyclosporine-methotrexate. Twenty-two patients relapsed at 3-46 months (median
      7): 18 of 76 patients with ABO-matched donors and four of 43 patients with ABO
      mismatched donors (actuarial 5-year probabilities 33 +/- 6% vs 12 +/- 6%; P =
      0.028). The incidence of acute and chronic GVHD was not affected by ABO mismatch.
      The following factors were studied in Cox analysis for effect on outcome: gender,
      age, FAB subtype, ABO mismatch, CR-transplant interval, conditioning, TBI dose,
      nucleated cell dose, lymphocyte recovery, acute GVHD, and chronic GVHD. Donor
      recipient ABO match was the only factor independently associated with a higher
      risk of relapse (RR = 3.7; 95% Cl, 1.1-12.6; P = 0.04). ABO mismatch was also
      associated with superior overall and disease-free survivals. We conclude that ABO
      incompatibility may influence relapse rates and survival favorably after
      allogeneic BMT. It is not known if this holds true for allogeneic blood stem cell
      transplants.

PMID- 12058236
TI  - Factors affecting progression-free survival in hormone-dependent metastatic
      breast cancer patients receiving high-dose chemotherapy and hematopoietic
      progenitor cell transplantation: role of maintenance endocrine therapy.
AB  - We retrospectively analyzed the effect of maintenance endocrine therapy (MET)
      after high-dose chemotherapy with hematopoietic progenitor cell transplant (HDCT)
      on the progression-free survival (PFS) of patients with hormone-dependent
      metastatic breast cancer (MBC). One hundred and nine consecutive patients with
      estrogen receptor (ER) and/or progesterone receptor (PgR)-positive MBC, who were
      progression free for at least 4 months after HDCT with cyclophosphamide,
      carmustine and thiotepa (CBT), were analyzed. Of these, 55 were non-randomly
      submitted to MET. After a median follow-up of 34.4 months (17.1-91.0), univariate
      analysis showed that MET was significantly associated with improved median PFS
      (31.1 vs 19.2 months, P = 0.022). Complete response to HDCT, pattern of
      metastatic spread, extent of the disease, single vs multiple metastatic sites,
      prior endocrine therapy for metastatic disease and prior exposure to any hormonal
      therapy (adjuvant and/or for the advanced disease) were also associated with PFS
      at univariate analysis. A multivariate Cox proportional hazard model was fitted
      to the data in order to correct the effect of MET for the other significant
      covariates. After correcting for these covariates, MET was still significant,
      predicting improved PFS (hazard ratio (HR) 0.580, 95% CI; 0.362-0.931).
      Administration of MET after optimal cytoreduction might result in increased
      efficacy of HDCT in hormone-dependent metastatic breast cancer.

PMID- 12058237
TI  - Fatal donor-derived Epstein-Barr virus-associated post-transplant
      lymphoproliferative disorder following reduced intensity volunteer-unrelated bone
      marrow transplant for myelodysplastic syndrome.
AB  - Post-transplant lymphoproliferative disorders (PTLD) are a well recognised
      complication of conventional haemopoietic stem cell transplantation (HSCT).
      Reduced intensity HSCT involves intensive immunosuppression to permit
      engraftment. Thirty reduced intensity transplants with the FBC (fludarabine 150
      mg/m2, busulphan 8 mg/m2, CAMPATH-1H 100 mg) protocol have been performed at our
      centre, with one confirmed EBV-positive PTLD. The female recipient developed a
      perforated viscus day +191 following HSCT from a volunteer unrelated male donor.
      A large caecal mass and a retroperitoneal abscess were excised, revealing an EBV
      positive diffuse large B cell lymphoma confirmed by FISH to be of donor origin.
      More experience is required before the risk of PTLD in this setting can be
      assessed.

PMID- 12058238
TI  - Successful treatment of refractory autoimmune haemolytic anaemia in a post
      unrelated bone marrow transplant paediatric patient with rituximab.
AB  - Here, we report a case of paediatric beta-thalassaemia major patient who
      underwent unrelated T cell-non- depleted bone marrow transplantation and
      developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to
      corticosteroid and intravenous immunoglobulin therapy. After this child received
      two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA
      was resolved.

PMID- 12058239
TI  - Polyvisceral arteritis in chronic graft-versus-host disease: antiphospholipid
      negative thrombotic syndrome mimicking polyarteritis nodosa.
AB  - A case of polyarteritis is reported in an 18-year old woman, occurring 2 years
      after an allogeneic bone marrow transplant. The clinical manifestations were
      similar to those of polyarteritis nodosa (PAN) with a wide range of organs
      involved including life-threatening cardiac and mesenteric problems requiring
      plasmapheresis and intravenous immunoglobulin (IgIV).

PMID- 12058240
TI  - Involvement of L-arginine/nitric oxide pathway at the paraventricular nucleus of
      hypothalamus in central neural regulation of penile erection in the rat.
AB  - The objective of this study is to investigate whether the L-arginine/nitric oxide
      pathway is involved in the neurotransmission of paraventricular nucleus of
      hypothalamus (PVN) activation-induced penile erection in the rat. Male adult
      Sprague-Dawley rats anesthetized with pentobarbital were used. The femoral artery
      was cannulated to measure systemic and mean arterial pressure (SAP and MAP), and
      heart rate (HR). A 26-gauge needle was inserted into corpus cavernosum to measure
      the intracavernous pressure (ICP) simultaneously with SAP, MAP and HR on a
      polygraph. Four groups of study were arranged: (1) stereotaxically delivery of L
      arginine (500 nmol/500 nl) into PVN; (2) administration of a mixture (1 microl)
      containing N(G)-Nitro-L-arginine methyl ester (L-NAME) 500 nmol and L-arginine
      500 nmol into PVN; (3) microinjection of saline 500 nl into PVN as a vehicle
      control; and (4) intracavernous injection of L-arginine (100 nmol/50 microl). The
      ICP, SAP, MAP and HR were monitored for at least 2 h after each administration of
      the experimental agents. Upon administration of L-arginine into PVN, there was a
      significant increase of ICP from resting 9.6+/-2.5 mmHg to peaked at 64.4+/-9.8
      mmHg after a latency of 3016.0+/-1749.7 s and with a duration of 27.6+/-15.8 min.
      There was no change of resting ICP after administration of the mixture of L-NAME
      and L-arginine into PVN. Application of saline to PVN and intracavernous
      injection of L-arginine failed to increase ICP. Based on elicitation of penile
      erection upon administration of L-arginine into PVN, and elimination of this L
      arginine induced penile erection by co-administration of L-NAME with L-arginine,
      the results of this study suggest that L-arginine/nitric oxide pathway may be
      involved in the neurotransmission of PVN activation-induced penile erection in
      the rat.

PMID- 12058241
TI  - Long-term results of Essed-Schroeder plication by the use of non-absorbable
      Goretex sutures for correcting congenital penile curvature.
AB  - This study evaluated the long-term outcome of the Essed-Schroeder procedure for
      correcting congenital penile curvature using non-absorbable Goretex sutures. The
      Essed-Schroeder procedure was performed in 35 patients with congenital ventral
      penile curvature (minimum 30 degrees ). Follow-up included a standardized
      interview with measurement of angulation. Twenty-three of 35 patients were
      available for complete long-term follow-up (average 34.3 months). The mean
      preoperative ventral curvature was 54 degrees. In 17/23 patients, the penis
      remained straightened. Recurrent curvature (average 23 degrees ) was observed in
      six of 23 patients. Fifteen of 23 patients complained of penile shortening
      (average 1.8 cm). Two of 23 patients reported disturbing side effects that were
      caused by plication nodes. In most cases, the results of penile straightening by
      the Essed-Schroeder procedure are excellent with a high grade of subjective
      satisfaction. Regarding the main problem, that is recurrent curvature, there is
      no decisive advantage of applying Goretex sutures. Discomfort caused by plication
      nodes can be reduced to a minimum by using a combination of soft Goretex sutures
      with the 'inverting stitch-technique'.

PMID- 12058243
TI  - Is there any relation between serum levels of total testosterone and the severity
      of erectile dysfunction?
AB  - The objective of this study was to correlate the severity of erectile dysfunction
      (ED) with the total testosterone serum levels (TT) in a normal population. During
      a screening program for the early diagnosis of prostate cancer, 1071 men aged
      from 40 to 90 y, were invited to answer the questionnaire of the Simplified
      International Index of Erectile Function (IIEF-5) as a method to diagnose and
      classify ED. The IIEF-5 scores ranged from 1 to 25 and the ED was classified into
      five groups according to the scores: severe (1-7), moderate (8-11), mild-moderate
      (12-16), mild (17-21) and no ED (22-25). Besides the questionnaire, all subjects
      had their TT serum levels determined based on the blood sample obtained between
      08:00 and 10:00. The analysis of the relationship between the different degrees
      of ED and TT levels was then studied. Of the 1071 men, 965 were included in the
      study (90.1%). Eighty-eight percent of these were Caucasian and 12% black. The
      mean age of the population was 60.7 y. The prevalence of all degrees of ED was
      53.9%. The degree of ED was mild in 21.5%, mild to moderate in 14.3%, moderate in
      6.3% and severe in 11.9%. The variation of TT serum concentrations was similar
      (P>0.05) in the different age groups. Furthermore, the TT serum levels were not
      different for individuals with and without ED (P>0.05) and similar concentrations
      of TT was observed in the different severity degrees of ED (P>0.05). Only one
      (0.7%) man in the group of individual with maximal score had subnormal levels of
      TT. ED presented a clear association with the subjects' aging, but neither
      correlation between TT levels and ED, nor with its severity, could be
      demonstrated in the present study.

PMID- 12058242
TI  - Catecholaminergic projections onto spinal neurons destined to the pelvis
      including the penis in rat.
AB  - In rats, the spinal cord contains proerectile autonomic motoneurons destined to
      the penile tissue and its vasculature, and somatic motoneurons destined to the
      perineal striated muscles. It receives dense catecholaminergic projections issued
      from the medulla and pons. In adult male rats, we evidenced the catecholaminergic
      innervation of spinal neurons controlling lower urogenital tissues and regulating
      penile erection. We combined retrograde tracing techniques and
      immunohistochemistry against synthetic enzymes of noradrenaline and adrenaline.
      Both sympathetic and parasympathetic preganglionic neurons, labeled from the
      major pelvic ganglion or from the corpus cavernosum, were apposed by
      catecholaminergic immunoreactive fibers. Motoneurons, retrogradely labeled from
      the striated muscles, were also apposed by catecholaminergic immunoreactive
      fibers. Synapses between these motoneurons and fibers were suggested by confocal
      microscopy and confirmed by electron microscopy in some cases. The results
      reinforce the hypothesis of a catecholaminergic control of autonomic and somatic
      motoneurons regulating penile erection at the spinal level.

PMID- 12058244
TI  - Significant decrease of the International Index of Erectile Function in male
      renal failure patients treated with hemodialysis.
AB  - In order to evaluate the erectile function in male renal failure patients treated
      with hemodialysis (HD), we investigated the International Index of Erectile
      Function (IIEF) in patients and healthy controls. The subjects were 174 male
      patients treated with HD, of whom 43 had diabetes mellitus (DM) and the remaining
      131 patients did not have DM. The controls were 1133 healthy males. We evaluated
      the prevalence of erectile dysfunction (ED) using the erectile function (EF)
      score, which is one of the five domains of the IIEF, in each age group (upto 39 y
      old, 40-49 y old, 50-59 y old, 60-69 y old). The severity of ED was classified
      into five categories using EF in each age group. The univariate logistic
      regression analysis and multiple variate analysis of IIEF in HD patients were
      performed. The prevalence of ED in HD patients was significantly higher than that
      in the controls in each age group. The severity of ED in HD patients was also
      significantly higher than that in the controls in each age group. In the logistic
      regression analysis and multiple variate analysis of IIEF in HD patients, DM and
      age were significant risk factors on sexual dysfunction. ED was more prevalent in
      male renal failure patients treated with HD than in the controls. In the patient
      group, ED was more prevalent in older DM patients.

PMID- 12058245
TI  - Interactions between drugs for erectile dysfunction and drugs for cardiovascular
      disease.
AB  - The association of erectile dysfunction (ED) and cardiovascular disease is well
      documented in the literature and both conditions share risk factors. Therefore,
      it is difficult to distinguish the effect of underlying disease and adverse
      effects of the drugs and/or interactions between ED drugs and drugs implemented
      for cardiovascular disease. The known interactions of systemic administered drugs
      for ED with drugs for cardiovascular disease are mainly pharmacodynamic. Thus,
      nitrates enhance the production of cyclic GMP and combined with phosphodiesterase
      type-5 inhibitors this can lead to severe hypotension. The same is the case for
      the treatment with phentolamine in patients treated with beta-adrenoceptor
      antagonists. Due to increased partial thromboplastin time, the risk of bleeding
      is enhanced for intracavernous alprostadil injection in heparin-treated patients.
      Pharmacokinetic interactions of clinical importance have been described for ED
      drugs with other therapeutic groups such as sildenafil with the antifungal drug,
      ketoconazole, and apomorphine with the antiparkinson drug, entacapon. Although
      sildenafil and antihypertensive dihydropyridines like amlodipine are metabolized
      by the same cytochrome P450 enzyme, CYP3A4 in the liver, the combination of these
      drugs does not exhibit a synergistic blood pressure lowering action.
      Unfortunately documentation concerning drug interactions is often poor and
      occasional.

PMID- 12058246
TI  - A shared care approach to the management of erectile dysfunction in the
      community.
AB  - Erectile dysfunction (ED) affects men of all ages and results in considerable
      distress and impact on quality of life for those who suffer from it. As ED is
      associated with a wide variety of under-lying conditions and cardiovascular co
      morbidities, there is a requirement for diversity of treatment options and
      several factors must be considered to customise and optimise therapy. In the
      ideal holistic approach to management of the ED patient, both primary care and
      specialist physicians have an important role to play. This article reports on a
      sequential approach for the diagnosis and treatment of ED, with an emphasis on
      'shared care'. The deliberations are based on a pan-European inter-disciplinary
      group that met at the Lygon Arms, UK on 22 February 2002.

PMID- 12058247
TI  - High flow priapism due to an arterial-lacunar fistula complicating initial veno
      occlusive priapism.
AB  - High flow or arterial priapism is rare, caused by unregulated arterial blood flow
      from a lacerated cavernous artery or branch entering directly into lacunar
      spaces, bypassing the protective, high resistance helicine arterioles and
      resulting in an arterial-lacunar fistula (ALF) and usually occurs following
      direct blunt or penetrating perineal trauma. Clinical features include delayed
      onset of a constant, painless, nontender erection of incomplete rigidity with
      potential for full rigidity with sexual stimulation. Colour duplex Doppler
      ultrasonography (CDU) is reliable in the diagnosis of arterial priapism.
      Treatment by arterial ligation, super-selective embolisation with autologous
      clot, gelatin sponge or microcoil, duplex guided compression, systemic or
      intracavernous administration of a variety of alpha-adrenergic agents or
      methylene blue, mechanical compression/ice packs or expectant management has been
      reported.

PMID- 12058248
TI  - Successful penile replantation following autoamputation: twice!
AB  - Report on a psychiatric patient who performed self-emasculation twice in an
      interval of 10 y. The penis was replanted microsurgically in both cases. At 1-y
      follow-up examinations he reported on restored erectile function. Under optimized
      therapy of his psychiatric disease, the patient appreciated the restored body
      image.

PMID- 12058249
TI  - Deep venous thrombosis and venous thrombophlebitis associated with alprostadil
      treatment for erectile dysfunction.
AB  - We report a patient who developed deep vein thrombosis of the calf and
      thrombophlebitis after treatment with intracorporeal alprostadil (Viridal). The
      reaction recurred on rechallenge with Viridal. This adverse effect has not been
      reported in the literature but six patients have been reported to the Medicines
      Control Agency in Great Britain. The history of deep venous thrombosis or
      thrombophlebitis may not be a formal contraindication to treatment with
      alprostadil, but the patient should be made aware of this possible complication
      before embarking on this form of treatment.

PMID- 12058250
TI  - The limited practical value of color Doppler sonography in the differential
      diagnosis of men with erectile dysfunction.
AB  - From the files of the outpatient urology department 44 men with ED had undergone
      both psychophysiological diagnostic screening (PDS, VSS, VSS+VIB, ICI+VSS+VIB)
      and color Doppler sonography testing (CDS, including VSS). PDS was carried out by
      one medical physiologist, CDS by one urologist. The diagnoses reached could be
      compared. This study revealed that CDS in ED-patients often resulted in an
      incorrect diagnosis, that is a presumed vascular abnormality while many such
      patients demonstrated firm erections under PDS-laboratory test conditions. Thus,
      it was concluded that CDS as a (first) screening test in ED-patients is of
      limited value. It was further emphasized that PDS, although giving quite relevant
      information about possible etiology and therapeutic treatment, is not a necessary
      first screen. Good history taking, preferably of the man and his partner, is
      still the basic first screen and quite often offers enough information to make a
      treatment plan with reasonable likelihood of success.

PMID- 12058252
TI  - Complex genetic control of susceptibility to malaria in mice.
AB  - Malaria is a major infectious disease worldwide, with over 1 million deaths in
      African children every year. The molecular pathways of pathogenesis of the
      Plasmodium parasite and the host mechanisms of defense against this infection
      remain poorly understood. Epidemiological studies, together with linkage analyses
      in endemic areas have clearly pointed at a genetic component of innate
      susceptibility and severity of disease. In humans, this genetic trait is complex,
      and has been studied in a mouse experimental model over the past few years.
      Inbred strains of mice show different degrees of susceptibility to infection with
      Plasmodium chabaudi, and the genetic component of these inter-strain differences
      has been studied in standard informative backcross and F2 populations, as well as
      in recombinant inbred strains and more recently, in recombinant congenic strains.
      These studies have shown that genetic susceptibility to malaria is also complex
      in mice, and have led to the mapping of major susceptibility Char (Chabaudi
      resistance) loci, located on chromosomes 9 (Char1), 8 (Char2), 17 (Char3) and 3
      (Char4).

PMID- 12058253
TI  - Separation and mapping of multiple genes that control IgE level in Leishmania
      major infected mice.
AB  - The strain BALB/cHeA (BALB/c) is a high producer, and STS/A (STS) a low producer
      of IgE after Leishmania major infection. We analyzed this strain difference using
      20 recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry
      different random subsets of 12.5% of genes of the strain STS on the BALB/c
      background. Strains CcS-16 and -20 exhibit a high and a low IgE level,
      respectively. In their F(2) hybrids with BALB/c we mapped nine Leishmania major
      response (Lmr) loci. Two of them we previously found to influence IgE level in
      CcS-5. IgE production in CcS-16 is controlled by loci on chromosomes 2, 10, 16
      and 18 and in CcS-20 by loci on chromosomes 1, 3, 4, 5 and 8. The STS alleles of
      loci on chromosomes 1, 4, 5, 8 and 10 were associated with a low, whereas the STS
      alleles on chromosomes 16 and 18 with a high IgE production. The loci on
      chromosomes 2 and 3 have no apparent individual effect, but interact with the
      loci on chromosomes 10 and 1, respectively. The loci on chromosomes 10 and 18
      were mapped in the regions homologous with the human regions containing genes
      that control total serum IgE and intensity of infection by Schistosoma mansoni,
      suggesting that some Lmr loci may participate in the pathways influencing atopic
      reactions and responses to several parasites. The definition of genes controlling
      anti-parasite responses will permit a better understanding of pathways and
      genetic diversity underlying the disease phenotypes.

PMID- 12058254
TI  - Identification of genetic loci controlling bacterial clearance in experimental
      Salmonella enteritidis infection: an unexpected role of Nramp1 (Slc11a1) in the
      persistence of infection in mice.
AB  - The Gram-negative bacteria, Salmonella, cause a broad spectrum of clinical
      diseases in both animals and humans ranging from asymptomatic carriage to life
      threatening sepsis. We have developed a model to study the contribution of
      genetic factors to the susceptibility of 129sv and C57BL/6J inbred mice to
      Salmonella enteritidis during the late phase of infection. C57BL/6J mice were
      able to eliminate completely sublethal inoculums of S. enteritidis from their
      reticuloendothelial system, whereas 129sv mice could not even after 60 days post
      inoculation. A genome scan performed on 302 (C57BL/6J x 129sv) F2 progeny
      identified three dominant loci (designated Ses1 to Ses3) that are associated with
      disease susceptibility in 129sv mice. Two highly significant linkages were
      identified on chromosomes 1 (Ses1) and 7 (Ses2) with respective LOD scores of 9.9
      (P = 1.4 x 10(-11)) at D1Mcg5 and 4.0 (P = 1.9 x 10(-5)) at D7Mit62. One highly
      suggestive QTL was located on chromosomes15 (Ses3) with a LOD score 3.4 (P = 1.2
      x 10(-4)). The estimated effects of Ses1, Ses2 and Ses3 on the bacterial
      clearance were greater in females. Using a model of three loci, with interaction
      between Ses1 and Ses2 and sex as a covariate, the three QTLs explained 32% of the
      phenotypic variance. The candidacy of Nramp1 as the gene for Ses1 was evaluated
      using mice carrying a null allele at Nramp1 (129sv-Nramp1(tm1Mcg)). These mice
      have a significantly lower spleen bacterial load compared to the wild-type 129sv
      mice, strongly suggesting the involvement of Nramp1 in controlling S. enteritidis
      clearance during the late phase of infection.

PMID- 12058255
TI  - Epistasis between DSG1 and HLA class II genes in pemphigus foliaceus.
AB  - Pemphigus foliaceus (PF) is a rare and severe cutaneous autoimmune disease caused
      by autoantibodies directed against desmoglein 1 (DSG1), a desmosomal adhesion
      glycoprotein. We previously showed that the DSG1 gene is polymorphic and that a
      coding synonymous T/C single nucleotide polymorphism at position 809 is
      associated with PF. To determine whether the disease occurred as a consequence of
      complex genetic interactions, we simultaneously examined the contribution of
      major histocompatibility complex (MHC) class II and DSG1 polymorphisms to PF
      susceptibility. Our analysis performed in 31 PF patients and 84 healthy controls
      first confirmed the previously reported common DRB1*04 and DRB1*14 genetic
      background in PF and individualized DRB1*0102, DRB1*0402 and DRB1*0406, and
      DRB1*1404 as susceptibility MHC class II alleles in French Caucasian PF patients.
      It also showed that the C/C(809) genotype was associated with PF. Combined
      analysis of HLA class II and DSG1 polymorphisms with several distinct statistical
      methods including logistic regression, showed that the DRB1*04 allele and the
      C/C(809) genotype interact to confer a higher susceptibility to PF. These data
      demonstrate the role of epistasis between individual genes in PF susceptibility
      and illustrate the genetic complexity of organ-specific autoimmune diseases.

PMID- 12058256
TI  - Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to
      multiple sclerosis, especially in selected combinations.
AB  - Multiple sclerosis (MS) is an autoimmune disease displaying different clinical
      courses. In this multifactorial disease complex environmental as well as genetic
      predisposition factors contribute to the disease manifestation. Following the
      candidate gene approach we analysed several genes of the NFkappaB cascade, which
      are prime candidates for MS because of their involvement in almost all
      immunological reactions. MS association was excluded for the NFKB1 and NFKB3
      genes, which show remarkably low degrees of polymorphism. The genes of NFkappaB
      inhibitors exhibit more sequence variations. In the IKBL gene a predisposing
      allele was identified (13.1% vs 7.5% in the control group, P < 0.001). This
      difference in the allelic distribution was even increased in the group of MS
      patients with a relapsing remitting course of the disease (14.9%, P < 0.0001). A
      protecting allele was found in the NFKBIA promotor for the patients with primary
      progressive MS (15.4% vs 28.4% in the control group, P < 0.01). Given
      predisposing alleles increase MS risk dramatically in certain combinations.

PMID- 12058257
TI  - Polymorphism in the STAT6 gene encodes risk for nut allergy.
AB  - Nut allergy is an important and potentially life threatening food allergy with a
      prevalence of one in 150 children in the UK population. STAT6 (signal transducer
      and activator of transcription) is an important molecule in the induction and
      regulation of an allergic response, which maps to chromosome 12q in a region
      previously linked with total serum IgE concentration and atopy in different
      populations. We have examined the frequency of a single nucleotide polymorphism
      (SNP) in the 3'UTR region of STAT6 gene in 71 UK Caucasoid patients diagnosed
      with nut allergy and 45 atopic patients without nut allergy using PCR-RFLP and
      compared these with 184 UK healthy controls. The STAT6 G allele frequency was
      significantly increased in nut allergy patients compared with blood donor
      controls (P < 0.0001, OR = 2.9, 95% CI: 1.7-4.9), which was under a recessive
      model (GG vs GA+AA, P = 0.0001, OR = 3.2, 95% CI: 1.7-5.8) but not in atopic
      patients without nut allergy. The G allele was most frequent in the severe cases
      and GG homozygosity was associated with the increased risk of severe reaction (OR
      = 3.9, 95% CI: 1.9-8.3). We conclude that STAT6 3'UTR polymorphism is associated
      with susceptibility and severity in nut allergic patients in our population.

PMID- 12058258
TI  - Association of the tumour necrosis factor alpha -308G/A polymorphism with the
      risk of diabetes in an elderly population-based cohort.
AB  - Ample evidence supports a role for tumour necrosis factor alpha (TNFalpha) in the
      development of type 2 diabetes and cardiovascular disease. TNFalpha expression
      was found to be influenced by a -308G/A polymorphism in the promoter of the gene
      encoding TNFalpha (TNF). We investigated the contribution of this polymorphism to
      diabetes and cardiovascular mortality in a population-based cohort of 664
      subjects aged 85 years and over (Leiden 85-plus Study). The -308G/A TNF promoter
      polymorphism was associated with the prevalence of diabetes in old age (P =
      0.006). The risk of diabetes among subjects homozygous for the A-allele was
      estimated to be 4.6-fold (95% CI, 1.6-13.3) higher than among subjects homozygous
      for the common G-allele. The promoter polymorphism did not, however, predict
      mortality from all causes, cardiovascular diseases, cancer or infectious diseases
      during a 10-year follow-up period. In addition to the promoter polymorphism, TNFa
      and TNFc microsatellite genotypes were determined but these polymorphisms were
      not associated with morbidity or mortality. In conclusion, the -308G/A
      polymorphism in the TNF promoter is strongly associated with the risk of diabetes
      but not cardiovascular mortality in old age.

PMID- 12058260
TI  - A CTLA-4 gene polymorphism at position -318 in the promoter region affects the
      expression of protein.
AB  - CTLA-4 is an important negative regulator of the immune system. The regulation of
      the CTLA-4 gene (Ctla-4) transcription is poorly understood. A single nucleotide
      polymorphism (SNP) at -318 in the Ctla-4 promoter region is associated with
      certain autoimmune diseases. Since the -318 SNP occurs in a potential regulatory
      region, it is conceivable that the C' T transition may affect the expression of
      Ctla-4. In the present study, we show that the -318T allele is associated with a
      higher promoter activity than the -318C allele (8.13 +/- 0.46 vs 6.87 +/- 0.49).
      The presence of the -318T allele may thus contribute to up regulation of the
      expression of CTLA-4, and consequently represent one mechanism to inhibit
      exaggerated immune activity.

PMID- 12058259
TI  - Influence of vascular endothelial growth factor single nucleotide polymorphisms
      on tumour development in cutaneous malignant melanoma.
AB  - Vascular endothelial growth factor (VEGF) is a potent regulator of vasculogenesis
      and tumour angiogenesis. We have investigated whether the VEGF -2578, -1154, +405
      and +936 SNPs and associated haplotypes confer susceptibility to and/or influence
      prognosis in cutaneous malignant melanoma (CMM) skin cancer. A total of 152 CMM
      patients and 266 controls were genotyped for VEGF promoter SNPs by ARMS-PCR.
      Strong linkage disequilibrium between the -2578, -1154 and +405 SNPs was detected
      (association, rho = 0.488-0.965), but not between these SNPs and SNP +936
      (association, rho = 0.004-0.130). No SNPs or three SNP haplotypes (-2578, -1154,
      +405) were significantly associated with CMM, although a number of non
      significant trends were observed. However, the VEGF -1154 AA genotype and -2578, 
      1154, +405 CAC haplotype were both significantly associated with less advanced
      (Stage 1) disease (P = 0.03). In addition, the VEGF -1154 AA genotype was
      associated with thinner primary vertical growth phase tumours (P = 0.002), while
      VEGF -1154 GG was associated with thicker primary tumours (P = 0.02). These
      preliminary results indicate that VEGF genotype may influence tumour growth in
      CMM, possibly via the effects of differential VEGF expression on tumour
      angiogenesis.

PMID- 12058262
TI  - A comparison of the effective dose from scanography with periapical radiography.
AB  - OBJECTIVES: To compare organ and effective doses from analogue scanographic and
      periapical radiography. METHODS: Thermoluminescent dosimeters (TLD-700) were
      inserted in the parotid glands (bilateral), submandibular glands (bilateral) and
      bone marrow (left ascending ramus) of three human cadavers. Dosimeters were also
      attached to the skin, thyroid gland and lens of both eyes. Central, left lateral
      and left posterior scanograms were obtained with a Cranex Tome (Soredex,
      Helsinki, Finland) multimodal imaging system. A similar procedure was applied for
      periapical radiographs of the midline, left lateral and left molar regions using
      E-speed film both with and without rectangular collimation. Organ and effective
      doses were calculated for scanograms and periapical radiographs. RESULTS: The
      effective doses for the scanograms were 0.001 mSv (central), 0.011 mSv (lateral)
      and 0.015 mSv (posterior). The effective doses for periapical radiographs were
      0.001 mSv (anterior), 0.001 mSv (lateral) and 0.003 mSv (posterior) for
      rectangular collimation and 0.001 mSv (anterior), 0.002 mSv (lateral) and 0.005
      mSv (posterior) for round collimation. CONCLUSIONS: When a larger area of the
      upper or lower jaw needs to be visualised, scanograms might be considered as an
      alternative to periapical radiography since the effective dose is lower.

PMID- 12058261
TI  - Imaging of biodegradable osteosynthesis materials by ultrasound.
AB  - OBJECTIVE: Biodegradable osteosynthesis materials are not radio-opaque and
      therefore not visible on conventional X-rays. The aim of this study is to
      investigate the use of ultrasound for imaging biodegradable materials to detect
      and monitor the degradation process. METHODS: Forty-six patients had two
      different polylactide osteosynthesis fracture plate materials used for the
      fixation of midfacial fractures. A 7.5 MHz ultrasound transducer with a 4.2 x 0.9
      cm footprint was used by two examiners at approximately 4-month intervals over 36
      months to monitor changes of the latero-orbital and infra-orbital rims. RESULTS:
      Intrinsically amorphous 50 : 50 poly(D,L)lactide reached the maximum of thickness
      (about 300% of the initial thickness) between 14 and 18 months post-implantation
      and was totally resorbed in clinical and ultrasound examinations 30 months post
      implantation. In 85 : 15 poly(L,D)lactide plates, the maximum of thickness (about
      300% of the initial thickness) was reached between 22 and 26 months post
      implantation and resorption was still in progress 36 months post-implantation.
      CONCLUSION: Ultrasound examinations are suitable for detecting and monitoring the
      degradation process of biodegradable osteosynthesis plates in the peri-orbital
      region.

PMID- 12058263
TI  - Survey of radiography and radiation protection in general dental practice in
      Uganda.
AB  - OBJECTIVES: To carry out the first survey in Uganda of all dentists and all
      public health dental officers (PHDO) to assess the status of dental radiography
      and radiation protection. METHODS: All 74 dentists and 76 PHDOs in Uganda were
      sent a postal questionnaire including 33 questions relating to various
      demographic details, radiographic equipment and radiographic techniques,
      including processing and radiation protection. A second questionnaire was sent to
      non-respondents after 3 months. RESULTS: Eighty-two per cent of dentists
      responded and 83% of PHDOs. Seventy per cent of the dentists and 100% of the
      PHDOs were trained in Uganda. Seventy-five per cent of the dentists and 30% of
      the PHDOs had access to one of the approximately 30 X-ray machines in the
      country. The majority of the equipment did not comply with current
      recommendations in Europe. Fifty-one per cent of dentists used machines with
      mechanical timers, 28% used machines with no visual warning signal and 17% used
      equipment with no audible warning signal. Most of the equipment was over 30 years
      old and only 15% of dentists knew when the equipment was last serviced. The most
      relevant finding of the surveys was the level of 'don't know' responses to many
      questions from both groups. CONCLUSIONS: The lack of knowledge regarding dental
      radiography and radiation protection plus the condition of most equipment in
      Uganda is a matter of concern. Standards of care are considerably lower than in
      developed countries requiring improved undergraduate training, provision of
      postgraduate courses and Ugandan governmental or international financial
      assistance.

PMID- 12058264
TI  - Accuracy of caries detection with four storage phosphor systems and E-speed
      radiographs.
AB  - OBJECTIVE: To evaluate the accuracy of caries detection using four intra-oral
      storage phosphor plate systems exposed with two different exposure times and one
      film system. METHODS: Under in vitro and standardised conditions 365 approximal
      and 159 occlusal surfaces were radiographed using four storage phosphor plate
      systems: DenOptix, Cd-dent, Digora (blue and white plates) and one film system:
      Ektaspeed Plus. The plates were exposed twice with 10% and 25% of the time needed
      for the film. Four observers recorded approximal enamel/dentine and occlusal
      dentine caries using a five-point confidence scale. Caries presence was validated
      histologically and diagnostic accuracy of the systems by using ROC curve areas
      (Az). RESULTS: The shorter exposure time for approximal caries,
      Digora(white)(Az=0.68) and Ekta Plus (Az=0.69) were significantly more accurate
      than the other systems (Az=0.64-0.65). For occlusal caries using the same
      exposure time, no significant difference was found between the digital systems
      (Az=0.76-0.77), which all showed to be significantly less accurate than Ekta Plus
      (Az=0.81). Using the longer exposure time for approximal caries, no significant
      difference was found between DenOptix (Az=0.68), Digora(blue) (Az=0.69),
      Digora(white) (Az=0.69) and Ekta Plus (Az=0.69) which were all significantly more
      accurate than Cd-dent (Az=0.65). For occlusal caries using the same exposure
      time, Digora(blue) (Az=0.81) was the most significantly accurate of the digital
      systems. When approximal caries was the diagnostic task, the longer exposure time
      resulted in significantly higher accuracy with the DenOptix and Digora(blue)
      systems but not with the Cd-dent and Digora(white) systems. For occlusal caries,
      the longer exposure time resulted in a significant improvement only with the
      Digora(blue) system. CONCLUSION: For approximal caries using the longer exposure
      time, no significant difference in diagnostic accuracy was found between
      DenOptix, Digora(blue), Digora(white) and Ekta Plus which were all significantly
      more accurate than the Cd-dent. For occlusal caries using the longer exposure
      time, Digora(blue) was found to be the most accurate of the digital systems. The
      exposure time had an influence on the diagnostic accuracy with the DenOptix and
      Digora(blue) systems for approximal and with the Digora(blue) system for occlusal
      caries detection.

PMID- 12058265
TI  - The accuracy and reliability of radiographic methods for the assessment of
      marginal bone level around oral implants.
AB  - OBJECTIVES: To determine the accuracy and reliability of radiographic methods for
      assessment of the marginal bone level around oral implants in human cadavers.
      METHODS: In three human cadavers two implants were placed according to the
      Instruction Manual for the Branemark System. One implant was installed in the
      canine and one in the premolar region of the left mandible. For each implant,
      conventional and digital intra-oral paralleling radiography were performed.
      Digital images were printed with a Kodak 1200 Distributed Medical Imaging printer
      on blue transparent film, glossy and plain paper. Furthermore, digital
      scanographic, panoramic and tomographic images were taken with the Cranex Tome
      multimodal X-ray unit and printed on Agfa Drystar TM 1 B transparent films. All
      images were evaluated by five dental specialists. Data were statistically
      compared with real measurements of the marginal bone level on the human cadavers,
      performed by the same group of observers. Intra- and inter-observer variability
      were determined. RESULTS: Digital intra-oral images on glossy paper showed the
      smallest absolute difference between real and measured bone level, followed by
      digital intra-oral images on film and on plain paper, conventional intra-oral
      images on analogue film, panoramic, scanographic and tomographic images on film.
      The difference between real and radiographic measurements was not statistically
      significant (P>0.05) for all radiographic techniques. Intra- and inter-observer
      reproducibility was high for all techniques. CONCLUSIONS: The selected imaging
      techniques showed an acceptable accuracy for peri-implant bone level measurements
      with an overall error of less than 0.5 mm. Intra-oral images showed the smallest
      absolute differences.

PMID- 12058266
TI  - Spontaneous resolution of simple bone cysts.
AB  - OBJECTIVE: To determine whether spontaneous resolution of simple bone cysts (SBC)
      is possible. METHODS: Ten patients were diagnosed as SBC on clinical and
      radiographic criteria and followed up for 1 to 7 years (mean 3.8). The degree of
      resolution was assessed subjectively by four radiologists and objectively by
      changes in the grey level histogram. RESULTS: All cases remained asymptomatic
      over the follow-up period. One of the lesions was considered static, two were
      increased, six remodeled and one resolved. The mean difference in grey levels
      between the lesion and the contralateral normal mandible decreased in 8 out of 10
      cases. CONCLUSION: It is probable that SBC resolves spontaneously. A protocol for
      clinical and radiographic diagnosis and follow-up is proposed.

PMID- 12058267
TI  - Virtual radiographs computed from TACT volume data as a gold standard for image
      registration prior to subtraction.
AB  - OBJECTIVE: To develop a three-dimensional (3D) model for quantitative analysis of
      image subtraction methods simulating clinical conditions and relevant to dental
      radiology. METHOD: A high-resolution volume representation of a formalin
      preserved segment of a human maxilla was synthesized from a set of 51 digital
      radiographs equidistantly covering the entire sampling aperture by means of Tuned
      Aperture Computed Tomography (TACT). Two-dimensional (2D) projection renderings
      of a 3D model were generated yielding arbitrary but well-known 2D projections
      with, and without, structured noise producing 'virtual radiographs'. RESULTS:
      Virtual radiographs were found to be similar to actual clinical images with
      respect to appearance, structure, and texture. Because the TACT reconstruction
      process allows all possible positions and orientations of source, specimen, and
      image plane to be simulated with negligible under sampling over a reasonable
      range of solid angles (sampling aperture), the resulting 3D model provided a
      rigorous method for establishing a truly objective gold standard (ground truth)
      for testing different registration techniques. CONCLUSIONS: TACT image
      registration can be assessed quantitatively by comparing actually observed vs
      theoretically professed parameters that presumably constrain the underlying
      projection geometries. Other attributes that vary from one method to the next,
      such as the use of nonlinear or region-specific techniques to facilitate
      registration, likewise, now can be rigorously measured by context-based methods
      such as quantitative determination of image similarity. Hence, a 3D model that
      renders idealized virtual radiographs from any desired projection geometry makes
      possible truly objective comparison of various digital subtraction techniques.

PMID- 12058268
TI  - Influence of room lighting on grey-scale perception with a CRT-and a TFT monitor
      display.
AB  - OBJECTIVES: To determine the influence of ambient lighting on grey-scale
      perception using a cathode-ray tube (CRT) and a thin film transistor (TFT)
      computer display. METHODS: A cathode ray tube (Nokia XS 446) and a liquid crystal
      display (Panasonic LC 50S) were used at reduced room lighting (70 lux) and under
      conditions recommended for a dental operatory (1000 lux). Twenty-seven observers
      examined twice a modified SMPTE test pattern [0 to 255; 255 to 0] grey-scale
      values. The corresponding contrast differences were allocated to four ranges of
      grey levels (I: 0-63; II: 64-127; III: 128-191; IV: 192-255). The influences of
      monitor type, grey-scale range and illumination were evaluated by means of
      repeated measures analysis of variance. RESULTS: Detection of differences in
      monochromatic intensity was significantly earlier with reduced lighting
      (P<0.0001). When full ambient lighting was used, the TFT display was superior
      compared to the CRT monitor in ranges II and III (P<0.0001), whereas no
      differences could be detected for grey intensities between 0 and 63 (P=0.71) and
      between 192 and 255 (P=0.36). CONCLUSIONS: Background lighting hampers grey-scale
      perception on computer displays. In this study of one TFT and one CRT monitor,
      the TFT in full ambient lighting was associated with earlier detection of grey
      scale differences than CRT.

PMID- 12058269
TI  - Lymphoepithelial lesion of the parotid gland.
AB  - We describe a case of lymphoepithelial lesion of the parotid gland, also known as
      salivary lymphoepithelial lesion. Lymphoepithelial lesions are usually seen in
      conjunction with autoimmune disease of the salivary glands and these lesions do
      not always remain benign. Our case consisted of two masses that had different
      imaging features. Moreover, we could investigate the changes of the size and
      internal architecture on imaging due to the postponement of surgical intervention
      on the masses. At review 6 months later, the size of the masses had increased.
      The aims of this paper were to: (1) investigate the contribution of gray-scale
      sonography, power Doppler sonography, magnetic resonance imaging, and computed
      tomography to the diagnosis; and (2) consider the appropriate imaging modality to
      follow-up this case to monitor for recurrence or malignant transformation.

PMID- 12058270
TI  - Denervation atrophy of the masticatory muscles in a patient with nasopharyngeal
      cancer: MR examinations before and after radiotherapy.
AB  - We report on a patient with denervation atrophy of the masticatory muscles due to
      nasopharyngeal cancer who received therapeutic irradiation. Magnetic resonance
      imaging has significantly contributed to aid diagnosis of this pathology.
      Masticatory muscle atrophy should be a definitive finding of perineural invasion
      caused by head and neck tumors. Radiologists should be familiar with this
      appearance to avoid confusion with tumor invasion of the muscle.

PMID- 12058271
TI  - Sialolith of unusual size and shape.

PMID- 12058273
TI  - Constitutive caspase-like machinery executes programmed cell death in plant
      cells.
AB  - The morphological features of programmed cell death (PCD) and the molecular
      machinery involved in the death program in animal cells have been intensively
      studied. In plants, cell death has been widely observed in predictable patterns
      throughout differentiation processes and in defense responses. Several lines of
      evidence argue that plant PCD shares some characteristic features with animal
      PCD. However, the molecular components of the plant PCD machinery remain obscure.
      We have shown that plant cells undergo PCD by constitutively expressed molecular
      machinery upon induction with the fungal elicitor EIX or by staurosporine in the
      presence of cycloheximide. The permeable peptide caspase inhibitors, zVAD-fmk and
      zBocD-fmk, blocked PCD induced by EIX or staurosporine. Using labeled VAD-fmk,
      active caspase-like proteases were detected within intact cells and in cell
      extracts of the PCD-induced cells. These findings suggest that caspase-like
      proteases are responsible for the execution of PCD in plant cells.

PMID- 12058274
TI  - The serine protease Omi/HtrA2: a second mammalian protein with a Reaper-like
      function.

PMID- 12058275
TI  - The farnesyltransferase inhibitor, FTI-2153, inhibits bipolar spindle formation
      during mitosis independently of transformation and Ras and p53 mutation status.
AB  - Recently, we have shown that the farnesyltransferase inhibitor FTI-2153 induces
      accumulation of two human lung cancer cell lines in mitosis by inhibiting bipolar
      spindle formation during prometaphase. Here we investigate whether this mitotic
      arrest depends on transformation, Ras and/or p53 mutation status. Using DAPI
      staining (DNA) and immunocytochemistry (microtubules), we demonstrate that in
      normal primary foreskin fibroblasts (HFF), as well as in several cancer cell
      lines of different origins including human ovarian (OVCAR3), lung (A-549 and Calu
      1) and fibrosarcoma (HT1080), FTI-2153 inhibits bipolar spindle formation and
      induces a rosette morphology with a monopolar spindle surrounded by chromosomes.
      In both malignant cancer cell lines and normal primary fibroblasts, the
      percentage of prometaphase cells with bipolar spindles decreases from 67-92% in
      control cells to 2-28% in FTI-2153 treated cells. This inhibition of bipolar
      spindle formation correlates with an accumulation of cells in prometaphase. The
      ability of FTI-2153 to inhibit bipolar spindle formation is not dependent on p53
      mutation status since both wild-type (HFF, HT1080 and A-549) and mutant (Calu-1
      and OVCAR3) p53 cells were equally affected. Similarly, both wild-type (HFF and
      OVCAR3) and mutant (HT1080, Calu-1 and A-549) Ras cells accumulate monopolar
      spindles following treatment with FTI-2153. However, two cell lines, NIH3T3 (WT
      Ras and WT p53) and the human bladder cancer cell line, T-24 (mutant H-Ras and
      mutant p53) are highly resistant to FTI-2153 inhibition of bipolar spindle
      formation. Finally, the ability of FTI-2153 to inhibit tumor cell proliferation
      does not correlate with inhibition of bipolar spindle formation. Taken together
      these results demonstrate that the ability of FTI-2153 to inhibit bipolar spindle
      formation and accumulate cells in mitosis is not dependent on transformation, Ras
      or p53 mutation status. Furthermore, in some cell lines, FTIs inhibit growth by
      mechanisms other than interfering with the prophase/metaphase traverse.

PMID- 12058276
TI  - Tissue distribution of Diablo/Smac revealed by monoclonal antibodies.
AB  - Diablo/Smac is a mammalian pro-apoptotic protein that can antagonize the
      inhibitor of apoptosis proteins (IAPs). We have produced monoclonal antibodies
      specific for Diablo and have used these to examine its tissue distribution and
      subcellular localization in healthy and apoptotic cells. Diablo could be detected
      in a wide range of mouse tissues including liver, kidney, lung, intestine,
      pancreas and testes by Western blot analysis. Immunohistochemical analysis found
      Diablo to be most abundant in the germinal cells of the testes, the parenchymal
      cells of the liver and the tubule cells of the kidney. In support of previous
      subcellular localization analysis, Diablo was present within the mitochondria of
      healthy cells, but released into the cytosol following the induction of apoptosis
      by UV.

PMID- 12058277
TI  - Redox factor-1: an extra-nuclear role in the regulation of endothelial oxidative
      stress and apoptosis.
AB  - The rac1 GTPase promotes oxidative stress through reactive oxygen species (ROS)
      production, whereas the DNA repair enzyme and transcriptional regulator redox
      factor-1 (ref-1) protects against cell death due to oxidative stimuli. However,
      the function of ref-1 in regulating intracellular oxidative stress, particularly
      that induced by rac1, has not been defined. We examined the role of ref-1 in
      vascular endothelial cell oxidative stress and apoptosis. Ref-1 was expressed in
      both the cytoplasm and nuclei of resting endothelial cells. Cytoplasmic ref-1
      translocated to the nucleus with the oxidative trigger hypoxia/reoxygenation
      (H/R). Forced cytoplasmic overexpression of ref-1 suppressed H/R-induced
      oxidative stress (H(2)O(2) production), NF-kappaB activation, and apoptosis, and
      also mitigated rac1-regulated H(2)O(2) production and NF-kappaB transcriptional
      activity. We conclude that inhibition of oxidative stress is another mechanism by
      which ref-1 protects against apoptosis, and that this is achieved through
      modulation of cytoplasmic rac1-regulated ROS generation. This suggests a novel
      extra-nuclear function of ref-1.

PMID- 12058278
TI  - Endoplasmic reticulum Ca(2+) signaling and calpains mediate renal cell death.
AB  - The goal of the current study was to determine the roles of ATP content,
      endoplasmic reticulum (ER) Ca(2+) stores, cytosolic free Ca(2+) (Ca(2+)(f)) and
      calpain activity in the signaling of rabbit renal proximal tubular (RPT) cell
      death (oncosis). Increasing concentrations (0.3-10 microM) of the mitochondrial
      inhibitor antimycin A produced rapid ATP depletion that correlated to a rapid and
      sustained increase in Ca(2+)(f), but not phospholipase C activation. The ER
      Ca(2+)-ATPase inhibitors thapsigargin (5 microM) or cyclopiazonic acid (100
      microM) alone produced similar but transient increases in Ca(2+)(f). Pretreatment
      with thapsigargin prevented antimycin A-induced increases in Ca(2+)(f) and
      antimycin A pretreatment prevented thapsigargin-induced increases in Ca(2+)(f).
      Calpain activity increased in conjunction with ER Ca(2+) release. Pretreatment,
      but not post-treatment, with thapsigargin or cyclopiazonic acid prevented
      antimycin A-induced cell death. These data demonstrate that extensive ATP
      depletion signals oncosis through ER Ca(2+) release, a sustained increase in
      Ca(2+)(f) and calpain activation. Depletion of ER Ca(2+) stores prior to toxicant
      exposure prevents increases in Ca(2+)(f) and oncosis.

PMID- 12058279
TI  - Inhibition of sperm production in mice by annexin V microinjected into
      seminiferous tubules: possible etiology of phagocytic clearance of apoptotic
      spermatogenic cells and male infertility.
AB  - Many differentiating spermatogenic cells die by apoptosis during the process of
      mammalian spermatogenesis. However, very few apoptotic spermatogenic cells are
      detected by histological examination of the testis, probably due to the rapid
      elimination of dying cells by phagocytosis. Previous in vitro studies showed that
      Sertoli cells selectively phagocytose dying spermatogenic cells by recognizing
      the membrane phospholipid phosphatidylserine (PS), which is exposed to the
      surface of spermatogenic cells during apoptosis. We examined here whether PS
      mediated phagocytosis of apoptotic spermatogenic cells occurs in vivo. For this
      purpose, the PS-binding protein annexin V was microinjected into the seminiferous
      tubules of normal live mice, and their testes were examined. The injection of
      annexin V caused no histological changes in the testis, but significantly
      increased the number of apoptotic spermatogenic cells as assessed by the terminal
      deoxynucleotidyltransferase-mediated dUTP nick end labeling assay. The number of
      Sertoli cells did not change in the annexin V-injected testes, and annexin V
      itself did not induce apoptosis in primary cultured spermatogenic cells. These
      results indicate that annexin V inhibited the phagocytic clearance of apoptotic
      spermatogenic cells and suggest that PS-mediated phagocytosis of those cells
      occurs in vivo. Furthermore, the injection of annexin V into the seminiferous
      tubules brought about a significant reduction in the number of spermatogenic
      cells and epididymal sperm in anticancer drug-treated mice. This suggests that
      the elimination of apoptotic spermatogenic cells is required for the production
      of sperm.

PMID- 12058281
TI  - Disialoganglioside GD3 is released by microglia and induces oligodendrocyte
      apoptosis.
AB  - Increased brain ganglioside levels are a hallmark of various neuroinflammatory
      pathologies. Here, we provide evidence that murine microglia can secrete
      disialoganglioside GD3 upon exposure to inflammatory stimuli. Comparison of
      different neural cell types revealed a particular and specific sensitivity of
      oligodendrocytes towards exogenous GD3. Oligodendrocyte death triggered by GD3
      was preceded by degeneration of cellular processes, and associated with typical
      features of apoptosis, such as chromatin condensation, exposure of
      phosphatidylserine, release of cytochrome c from mitochondria, and loss of
      mitochondrial membrane potential, followed by the loss of plasma membrane
      integrity and detachment of disintegrated oligodendrocytes. Overexpression of bcl
      2 partially protected oligodendrocytes from death. In contrast, treatment with
      the pan-caspase inhibitor zVAD-fmk did not prevent phosphatidylserine exposure,
      chromatin margination at the nuclear periphery, and death, although caspase-3 was
      blocked. Thus, GD3 produced by microglia under neuroinflammatory conditions may
      function as a novel mediator triggering mitochondria-mediated, but caspase
      independent, apoptosis-like death of oligodendrocytes.

PMID- 12058280
TI  - Defective Bax activation in Hodgkin B-cell lines confers resistance to
      staurosporine-induced apoptosis.
AB  - Deregulated apoptosis represents an important hallmark of tumor cells. Here we
      investigated the induction of cell death signaling pathways in cell lines
      previously established from patients with Hodgkin's disease. Our data show that
      Hodgkin's disease derived B-cell lines uniformly proved resistant to
      staurosporine, a protein kinase C inhibitor that preferentially stimulates the
      mitochondrial apoptotic pathway. Contrary to control cell lines, staurosporine
      failed to induce cytochrome c release from mitochondria in Hodgkin derived B
      cells. Correspondingly, activation of caspases was not observed in these cells.
      In staurosporine-treated Hodgkin cells Bax remained in its inactive state,
      indicating that these cell lines have a defect in this crucial step in apoptotic
      signaling upstream of the mitochondria. Our results suggest that the failure to
      activate Bax might represent a common defect of Hodgkin tumor cells of the B-cell
      lineage.

PMID- 12058284
TI  - [Surgical decompression of branch retinal vein occlusion].

PMID- 12058283
TI  - Death in paradise.

PMID- 12058282
TI  - Prevention of cytokine-induced apoptosis by insulin-like growth factor-I is
      independent of cell adhesion molecules in HT29-D4 colon carcinoma cells-evidence
      for a NF-kappaB-dependent survival mechanism.
AB  - We have previously established that insulin-like growth factor (IGF)-I, -II and
      insulin exert a strong protective effect against tumor necrosis factor-alpha
      (TNF)-induced apoptosis in interferon-gamma (IFN)-sensitized HT29-D4 human colon
      carcinoma cells. In this study, we report that this effect was still operative
      when cells were cultured in the absence of integrin- and E-cadherin-mediated cell
      extracellular matrix and cell-cell interactions. In this model, IGF-I did not
      activate the focal adhesion kinase, whereas it induced tyrosine phosphorylation
      of the insulin receptor substrate-1 and activation of the extracellular signal
      related kinase 1 and 2, p38, phosphatidylinositol 3'-kinase and protein kinase
      B/Akt. However, the use of specific inhibitors indicated that these pathways did
      not play a role in the adhesion-independent IGF-I anti-apoptotic signal. In
      contrast, inhibition of the NF-kappaB activation induced a complete reversal of
      the IGF-I anchorage-independent protective effect. Correspondingly, IGF-I
      markedly enhanced the TNF- and IFN/TNF-induced NF-kappaB-dependent interleukin-8
      production. Our results provide evidence that IGF-I induces resistance against
      cytokine-induced cell death even in the absence of cell adhesion-mediated
      signaling. NF-kappaB appears to be a key mediator of this anti-apoptotic effect
      that should contribute to the resistance of colon cancer cells to immune
      destruction during metastasis.

PMID- 12058285
TI  - Trends in neuroprotection.

PMID- 12058286
TI  - [Variability in the effects of topical cycloplegics].

PMID- 12058287
TI  - [Ocular sarcoidosis. Retrospective study of 18 cases].
AB  - PURPOSE: To assess the clinical and epidemiological characteristics, diagnostic
      and therapeutic methods, and the final visual outcome of a group of patients with
      ocular sarcoidosis. METHODS: Retrospective study of 18 patients diagnosed of
      ocular sarcoidosis between March 1989 and May 1999. In every patient the
      following data were obtained: age, sex, bilaterality, initial and final visual
      outcome, systemic and ocular manifestations, stage of chest x-ray, serum markers,
      gallium scan, results of biopsy, medical and surgical treatment, and
      complications of treatment. RESULTS: The mean age at onset was 49.7 years (S.D.
      19.9). Fourteen patients (77.8%) were female and 4 (22.2%) were male. The average
      follow-up time was 40.3 months (S.D. 28.7). Nine patients (50.0%) underwent a
      biopsy. The presence of non-caseating granulomata was observed in 7 (77.8%).
      Gallium scanning was positive in 16 cases (88.8%). The most frequent ocular
      manifestation was panuveitis (40.0%). Among the 30 eyes studied, conjunctival
      involvement was found in 10 (33.3%), secondary cataracts in 9 (30.0%), and
      secondary glaucoma in 6 (20.0%). Eleven patients (61.1%) were treated with oral
      corticosteroids and 10 (55,5%) with cyclosporine A. When sarcoidosis was
      diagnosed, 11 eyes (36.6%) had a visual acuity better than 0.6. At the end of the
      follow-up, the final visual outcome was better than 0.6 in 17 eyes (56.6%).
      CONCLUSIONS: An adequate control of ocular inflammation may improve the prognosis
      in patients with ocular sarcoidosis. Posterior segment involvement (posterior
      uveitis, macular edema or epiretinal membrane) may be associated with a worse
      visual prognosis.

PMID- 12058288
TI  - [Intraocular pressure asymmetry and related factors in pseudoexfoliative
      syndrome].
AB  - PURPOSE: To determine the intraocular pressure (IOP) asymmetry in
      pseudoexfoliative (PSX) syndrome and glaucoma patients. To analyze the
      association between IOP asymmetry and clinical signs. METHODS: 191 patients were
      prospectively studied, 75 (39.3%) with PSX syndrome and 116 (60.7%) with PSX
      glaucoma. IOP, visual field test, pigment and PSX material deposit in anterior
      segment structures were observed and compared between both eyes. The relation
      between IOP and clinical sign asymmetry was analyzed. RESULTS: IOP asymmetry was
      less than 10 mm Hg in 138 cases (72.25%) and more than 10 mm Hg in 53 (27.75%)
      cases. The greatest asymmetry was found in unilateral PSX glaucoma patients (p=
      0.001). Visual field test asymmetry was related with IOP asymmetry (p=0.0001).
      Also, IOP asymmetry was associated with pigment deposit in trabecular meshwork,
      in Sampaolesi line, and with pupillary atrophy asymmetry (p<0.05). PSX material
      deposit was not related with IOP asymmetry. CONCLUSIONS: IOP asymmetry is greater
      in unilateral PSX glaucoma patients. The association between IOP and visual field
      test asymmetry found in this study suggests that PSX glaucoma is pressure
      dependent. IOP seems to be related with pigment deposit in anterior segment
      structures in PSX patients. However, this association was not found with PSX
      material deposit.

PMID- 12058289
TI  - [Scleral surgery of retinal detachment without drainage of subretinal fluid and
      no cryotherapy].
AB  - PURPOSE: To evaluate anatomic and functional results in patients treated for
      uncomplicated rhegmatogenous retinal detachment (RD) with scleral surgery without
      the use of subretinal fluid (SRF) drainage and using no cryotherapy. MATERIAL AND
      METHOD: We present a retrospective study of 76 patients who underwent RD scleral
      surgery without cryotherapy or SRF drainage. We analyze postoperative outcomes
      and the incidence of intraoperative and postoperative complications. RESULTS: The
      average of our retinal reapplications totals 90.78%, which is similar to those
      described by other types of surgical techniques, while our intraoperative and
      postoperative complications are dramatically reduced including improvement of
      functional results. CONCLUSIONS: Scleral surgery for retinal detachment using no
      drainage of subretinal fluid nor cryotherapy is a useful technique for the
      treatment of RD.

PMID- 12058290
TI  - [Initial findings with pulsar perimetry in patients with ocular hypertension].
AB  - PURPOSE: To evaluate our first results with Pulsar perimetry in patients with
      ocular hypertension and compare them with normal individuals. METHODS: We studied
      34 eyes of patients with ocular hypertension and normal G1 Octopus perimetry
      (mean age: 57.29 S.D. 10.55) and 41 eyes of normal individuals (mean age: 48.34
      S.D. 13.71). A complete ophthalmologic examination, including Dr. Gonzalez de la
      Rosa's Pulsar perimetry with TOP strategy, was performed for all patients.
      EXCLUSION CRITERIA: visual acuity <0.8, refractive defect 3 spheric dp or 1.5
      astigmatic dp, pupil size <3 mm, ocular surgery or pathologies, non-controlled
      diabetes or neurological diseases. They all had previous perimetric experience.
      Results were analyzed with student t - test. RESULTS: For normal individuals,
      mean sensitivity (MS) for Pulsar perimetry was 21,25 src (spatial resolution and
      contrast units) with an S.D. of 2,70. Mean defect (MD) was 0,93 src S.D. 1,80 and
      loss variance (LV) was 6,11 src S.D. 4,30. For patients with ocular hypertension:
      MS was 18,65 src S.D. 2,79; MD was 2,73 src S.D. 2,30 and LV was 8,46 src S.D.
      5,01. LV differences between the two groups were statistically significant
      (p<0.05) with 95% confidence limits of (-4.49; -0.20), and MS and MD differences,
      highly significant (p<0.01), with 99% confidence limits of (+0.92; +4.28;) and (
      3.05; -0.54) respectively. CONCLUSIONS: Pulsar perimetry may have greater
      sensibility for the detection of early defects in patients with ocular
      hypertension than conventional perimetry.

PMID- 12058291
TI  - [Bilateral acute retinal necrosis due to herpes simplex virus in inmunocompetent
      people and acyclovir resistance].
AB  - CASE REPORT: A twenty-eight year old woman with necrotitizing retinitis and
      herpes simplex virus type 1 isolated in aqueous humor with polymerase chain
      reaction (PCR). An Acyclovir and corticosteroid therapy was started with
      unsuccessful response, Foscarnet was added getting quiescence of lesions.
      DISCUSSION: Acute Retinal Necrosis Syndrome (ARNS), induced by a virus of the
      herpes family, could develop in immunocompetent people. A characteristic clinical
      case with uveitis and vitritis, white retinitis areas and occlusive vasculitis is
      reported. Antiviral therapy with acyclovir and antiinflammatory treatment must be
      established quickly. Foscarnet can effectively treat ARNS in inmunocompetent
      patients. In spite of therapy, this is a potentially blinding retinal disease.

PMID- 12058292
TI  - [Ocular decompression retinopathy after trabeculectomy].
AB  - PURPOSE: Two cases of ocular decompression retinopathy associated with glaucoma
      filtering surgery are described. CONCLUSIONS: Both patients were young males,
      intraocular pressures were 35 and 40 mm Hg before surgery. The retinal
      haemorrhages resolved, and in the only case where it was possible to estimate the
      visual acuity, it had improved significantly. In the few cases that were
      reported, most involve young males with markedly high intraocular pressures
      before surgery and occasionally myopic.

PMID- 12058295
TI  - [Intraoperative neuromonitoring in thyroid surgery and surgery of the parathyroid
      gland].

PMID- 12058296
TI  - [Does intraoperative nerve monitoring reduce the rate of recurrent nerve palsies
      during thyroid surgery?].
AB  - Two different aspects of the influence of neuromonitoring on the possible
      reduction of post-operative recurrent laryngeal nerve palsies require critical
      examination: the nerve identification and the monitoring of it's functions. Due
      to the additional information from the EMG signals, neuromonitoring is the best
      method for identifying the nerves as compared to visual identification alone.
      There are still no randomized studies available that compare the visual and
      electrophysiological recurrent laryngeal nerve detection in thyroid operations
      with respect to the postoperative nerve palsies. Nevertheless, comparisons with
      historical collectives show that a constant low nerve-palsy-rate was achieved
      with electrophysiological detection in comparison to visual detection. The rate
      of nerve identification is normally very high and amounts to 99 % in our own
      patients. The data obtained during the "Quality assurance of benign and malignant
      Goiter" study show that in hemithyreoidectomy and subtotal resection, lower nerve
      palsy-rates are achieved with neuromonitoring as compared to solely visual
      detection. Following subtotal resection, this discrepancy becomes even
      statistically significant. While monitoring the nerve functions with the
      presently used neuromonitoring technique, it is possible to observe the EMG
      signal remaining constant or decreasing in volume. Assuming that a constant
      neuromonitoring signal represents a normal vocal cord, our evaluation shows that
      there is a small percentage of false negative and positive results. Looking at
      the permanent recurrent nerve palsy rates, this method has a specificity of 98 %,
      a sensitivity of 100 %, a positive prognostic value of 10 %, and a negative
      prognostic value of 100 %. Although an altered neuromonitoring signal can be
      taken as a clear indication of eventual nerve damage, an absolutely reliable
      statement about the postoperative vocal cord function is presently not possible
      with intraoperative neuromonitoring.

PMID- 12058297
TI  - [Results of laryngeal nerve monitoring during thyroid operations--Studies and
      value for clinical practice].
AB  - Injuries of the laryngeal nerve still remain a source of morbidity for patients
      undergoing surgery for the thyroid gland. The incidence of permanent damage of
      the nerve varies from 0.5 % to 2.7 % depending on the series, but for special
      thyroid diseases like thyroid carcinoma or goiter recurrence the damage of the
      recurrent laryngeal nerve could be up to 25 %. For that reason several methods of
      monitoring the movement of the nerve while stimulation have been proposed. Such
      as inserting a needle into the vocal muscles or working with a surface laryngeal
      electrode that is attached above the cuff of the tube. For neither of those
      methods of nerve monitoring severe complications were described. The purchase
      costs for all the equipment are between 25.000 to 30.000 DM. All the published
      data regarding monitoring of the laryngeal nerve have been only observation
      studies with no control group and for that reason the results of the studies
      could not be obligatory statements. Furthermore not every nerve palsy has been
      identified by the monitoring of the laryngeal nerve, this method has a
      sensitivity of less than 70 %. Monitoring of the laryngeal nerve is a helpful
      clinical tool not only for training of surgeons but also during complicated
      thyroid surgery. Monitoring is especially useful for operations of thyroid
      carcinoma or revision procedures. But at the moment there is no randomised study
      available that shows any superiority of this new and expensive method over the
      standard therapy, therefore further studies are necessary. Until these studies
      exist the anatomical localisation of the nerve during surgical dissection is
      still the gold standard.

PMID- 12058298
TI  - [Reliabilty of intraoperative recurrent laryngeal nerve monitoring in thyroid
      surgery].
AB  - INTRODUCTION: The intraoperative monitoring of the recurrent laryngeal nerve
      (NLR) is increasingly used in thyroid surgery. What has the surgeon to know about
      reliability and peculiarity of this method? PATIENTS AND METHOD: Between 11/98
      and 3/01 417 patients were operated for thyroid pathology. Vocal cord function
      was controlled pre- and postoperatively in all cases by laryngoscopy.
      Intraoperative electromygraphic NLR identification and postoperative vocal cord
      function were registered prospectively. RESULTS: Intraoperative NLR
      identification succeeded in 98.9 % (776/784 nerves at risk). Minor vocal cord
      dysfunctions were demonstrable for less than 4 weeks in 13 patients (1.6 %)
      associated with edema or hematoma in 11/13 cases. Complete unilateral NLR pareses
      was seen laryngoscopically in 16 patients (2 %). 1 patient revealed a malignant
      NLR infiltration. Electromygraphic NLR identification wasn't possible and
      followed by postoperative NLR palsy in 2 patients. In 11/13 cases with a regular
      intraoperative monitoring postoperative vocal cord function recovered within 8
      weeks. In 2 of 4 NLR pareses persisting at the moment the follow up is longer
      than 12 months (permanent palsy rate 0.25 %). CONCLUSIONS: NLR identification
      during thyroid surgery is improved by intraoperative monitoring. In cases with
      difficult thyroid preparation the vagal nerve may be stimulated for indirect
      proof of NLR integrity.

PMID- 12058299
TI  - [A Critical Estimation of Intraoperative Neuromonitoring (IONM) in Thyroid
      Surgery].
AB  - We investigated 238 patients with 431 nerves at risk (NAR) undergoing thyroid
      surgery. Positive identification of the recurrent laryngeal nerve was obtained in
      99.3 % of NAR with intraoperative neuromonitoring. 19 patients (4.4 % NAR)
      suffered from unilateral vocal cord dysfunction in the early postoperative phase.
      A complete restitution of vocal cord function could be demonstrated in 18 of
      these patients, leaving one patient (0.23 % NAR) with a permanent vocal cord
      dysfunction. Our data show that reliable predictions concerning the postoperative
      outcome of nerve function cannot always be made on the basis of the
      intraoperative findings. Thus, our own data show a specifity of 98.5 % and a
      negative predictive value of 96.8 %. On the other hand, sensitivity was 23.5 %
      and positive predictive value was 40 %. Misinterpretation of the intraoperative
      signal can lead to risky operative manoeuvres. Possible reasons for the
      misinterpretation of the intraoperative signal and a critical reflection on the
      possibilities and predictive values of neuromonitoring will be discussed.

PMID- 12058300
TI  - [Intraoperative electrophysiological monitoring of the recurrent laryngeal nerve
      in thyroid gland surgery--a prospective study].
AB  - INTRODUCTION: In the last few years the use of intraoperative
      electrophysiological monitoring of the recurrent laryngeal nerve (RLN) in thyroid
      gland surgery has become more and more important. PATIENTS AND METHOD: In a
      prospective study 223 nerves at risk in 116 patients were monitored with the
      Neurosign(R)100 (Fa. Magstim Ltd., UK). We used intramuscular needle electrodes
      inserted into the vocal muscle through the conic ligament. Practicability,
      complications, acceptance and predictive value of the method were documented.
      Recurrent nerve palsy rate and complications were compared with a control group
      operated upon without monitoring. RESULTS: The intraoperative delay using this
      method was on average 8.9 minutes. There were problems with monitoring equipment
      avoiding use in 6.4 %. In 2 cases (1.7 %) an accidental lesion of endotracheal
      tube cuff was found related to malpositioning of the needle and in 7.7 % a
      hematoma of the vocal cords was observed. 73.3 % of the surgeons accepted the
      method to identify and control the nerve integrity. False-positive and false
      negative signals may occur. In cases of a final real stimulus response a regular
      vocal cord motility was found in 95 %. If a nerve conduction block was noted an
      immobility of ipsilateral vocal cord was diagnosed postoperatively in 50 %. There
      was no decrease in transient recurrent palsy rate using monitoring (10.7 % vs.
      9.6 % without monitoring) but in permanent paralysis (1.8 % vs. 3.0 %).
      CONCLUSIONS: It may be concluded that intraoperative electrophysiological
      monitoring of the RLN is a simple and accepted method with low complications
      reducing the incidence of permanent RLN palsy rate. We found the monitoring
      especially useful for operations of recurrent goiter and carcinomas of the
      thyroid gland as well as for learning thyroid gland surgery.

PMID- 12058301
TI  - [Neuromonitoring of the recurrent laryngeal nerve--a critical analysis of
      patients with postoperative nerve palsy].
AB  - The transligamental intraoperative neuromonitoring of the recurrent nerve is
      established in many surgical clinics as an useful and reliable technique. It is
      especially suitable to identify the recurrent nerve and to monitor its function
      during thyroid operation. We have analysed 14 early postoperative recurrent nerve
      palsies between June 1997 and December 2000 (1,23 % related to nerves at risk).
      As a result of complete follow up we found 4 permanent nerve palsies (0,35 %
      related to nerves at risk). In 11 out of 14 cases the neuromonitoring revealed a
      dysfunction of the recurrent nerve. The following long distance microsurgical
      preparation showed no interruption of the continuity of the nerve. Knowing the
      fact of unilateral negative monitoring signal we adapted our operative strategy.
      Therefore we did not observe bilateral nerve palsies. In 3 patients we found a
      positive nerve signal but nevertheless these patients showed postoperative
      unilateral recurrent palsies. The possible reasons are discussed. We are
      convinced that the neuromonitoring of the recurrent laryngeal nerve is an
      important progress in thyroid surgery.

PMID- 12058302
TI  - [Identification and surgical anatomy of the external branch of the superior
      laryngeal nerve].
AB  - Injury to the external branch of the superior laryngeal nerve (EBSLN) during
      thyroid surgery can cause serious consequences for patients who depend on control
      of pitch and a clear and forceful voice, like singers or professional speakers.
      We used the Neurosign 100(R) nerve monitor to identify 157 nerves in 108 patients
      undergoing thyroid surgery. The EBSLN was successfully identified in 98.7 % of
      cases. The recording electrode could be placed either into the cricothyroid
      muscle or the vocal cord. The latter position proved superior if the recurrent
      laryngeal nerve had to be identified as well. 16 percent of the nerves crossed
      the branches of the superior thyroid artery at or below the upper pole of the
      gland, posing a "high risk" for intraoperative lesions. Our data confirm the
      results of smaller studies reporting this type of nerve course in 12 % to 14 % of
      patients. The present findings show a significant number of EBSLN to be in danger
      of injury when the superior thyroid artery is ligated during thyroid surgery.
      Neuromonitoring proofed to be a reliable method to identify the nerve, which is
      an important element in concepts to prevent its injury.

PMID- 12058304
TI  - [Is the timing of completion thyroidectomy for differentiated thyroid carcinoma
      prognostic significant?].
AB  - The purpose of this study was to evaluate whether the timing of completion
      thyroidectomy for differentiated thyroid carcinoma had an influence on the risk
      of the operation and patient's survival. From January 1, 1985 to March 31, 2001,
      230 consecutive patients underwent surgery for differentiated thyroid carcinoma
      (178 papillary and 52 follicular carcinomas). In this article completion
      thyroidectomy was defined as the removal of the remaining thyroid tissue after
      any initial surgical procedure less than total thyroidectomy within an interval
      ranging from 3 days to 4 months after the initial surgical procedure. Of 99.1 %
      (n = 228) of the 230 patients the postoperative course is known for 1 month to 36
      years with a median follow-up of 5 years. Among 81 patients undergoing
      thyroidectomy as the initial operation, recurrent laryngeal nerve palsy occurred
      in 13.5 % (n = 11). In 2 of these patients (2.5 %) recurrent laryngeal nerve
      palsy was permanent. Transient recurrent laryngeal nerve palsy occurred more
      frequent in patients who underwent completion thyroidectomy within 8 days to 3
      months of the initial surgical procedure (20.5 %) than in patients, in whom
      completion thyroidectomy was performed either within 7 days of the primary
      operation or after a minimum of 3 months (5.2 % in each group). Disease-free
      survival as well as long-term survival was not different after thyroidectomy or
      completion thyroidectomy for all differentiated thyroid carcinomas and in
      patients with papillary carcinomas. In order to reduce surgical morbidity we
      suggest that completion thyroidectomy should be performed either within 7 days of
      the primary operation or after a minimum of 3 months.

PMID- 12058303
TI  - [Dysfunction of calcium metabolism following resection of the thyroid gland. An
      analysis of important risk factors].
AB  - PURPOSE: Dysfunction of the parathyroid glands is a typical complication
      following thyroid surgery. Risk factors for the development of postoperative
      symptomatic hypocalcemia were retrospectively analyzed. METHODS: 308 consecutive
      thyroid resections (women n = 236, men n = 72, mean age 53 years) performed in
      1996 and 1997 were evaluated. Main diagnosis was non-toxic nodular goiter (n =
      234, 76 %), 28 patients (9 %) had thyroid carcinoma. The most common operation
      performed was bilateral functional thyroid resection (n = 116, 38 %), the
      proportion of thyroidectomies was 14 % (n = 44). The patients with postoperative
      symptomatic hypocalcemia were followed for a median of 32 months. RESULTS:
      Clinical symptoms of hypocalcemia were observed in 18 patients (6 %)
      postoperatively. Three patients developed transient (n = 1) or permanent
      hypothyroidism (n = 2). In univariate analysis, the underlying thyroid disease,
      the method of operative therapy, removal, identification and autotransplantation
      of parathyroid glands, in multivariate analysis, thyroidectomy (relative risk
      6.9) and removal of parathyroid glands (relative risk 23.9) were proved to be
      significant risk factors for the development of postoperative symptomatic
      hypocalcemia (p < 0.05). CONCLUSIONS: Patients with thyroidectomy, operation for
      thyroid carcinoma and intraoperative removal of parathyroid glands should be
      closely followed for postoperative hypocalcemia. Exact surgical technique
      provided, permanent hypoparathyroidism is rare, particularly if several
      parathyroid glands were identified intraoperatively and autotransplanted, if
      necessary.

PMID- 12058305
TI  - [Autotransplantation of at least one parathyroid gland during thyroidectomy in
      benign thyroid disease minimizes the risk of permanent hypoparathyroidism].
AB  - OBJECTIVE: Permanent hypoparathyroidism is a distressing complication of thyroid
      surgery. The reported incidence varies between 0.4 and 13.8 % and is directly
      correlated to the extent of thyroidectomy. The aim of this retrospective study
      was to analyze whether simultaneous autotransplantation of at least one
      parathyroid gland during total thyroidectomy for benign thyroid disease could
      reduce the risk of permanent hypoparathyroidism. METHODS: Since 01/1999 all
      thyroid operations are prospectively recorded. Beside daily postoperative
      measurement of serum calcium level, iPTH is routinely determined on the third
      post op day. Patients with complications are followed closely. Postoperative
      hypoparathyroidism persisting for more than 6 months is defined permanent.
      RESULTS: Between 01/1999 and 02/2001 146 total thyroidectomies for benign thyroid
      disease have been performed (81 pat. with Graves disease, 62 with nodular goiter,
      3 with thyroiditis de Quervain/Hashimoto). In 37 pat. (25 %) at least one
      parathyroid gland was simultaneously autotransplanted into the ipsilateral
      sternocleidomastoid muscle. Group I (no parathyroid autotransplantation, n = 109)
      and group II (parathyroid autotransplantation, n = 37) were comparable concerning
      patient age, thyroid disease and lowest post op calcium level (2.07 versus 2.05
      mmol/l). The incidence of postoperative symptomatic hypocalcemia (14.7 % versus
      21.6 %) and temporary hypoparathyroidism (15.6 % versus 18.9 %) was higher in
      group II patients (n. s.). Conversely, permanent hypoparathyroidism occurred
      exclusively in group I patients (2.75 %), patients with parathyroid
      autotransplantation (group II) did not develop this complication. CONCLUSIONS:
      Simultaneous autotransplantation of at least one parathyroid gland during total
      thyroidectomy for benign thyroid disease seems to minimize the risk of permanent
      hypoparathyroidism. The potential of routine autotransplantation in this setting
      has to be evaluated. The incidence of postoperative temporary hypocalcemia may be
      elevated with this policy.

PMID- 12058306
TI  - [Patient selection criteria for single-sided or minimal invasive operative
      procedures in primary hyperparathyroidism (pHPT)].
AB  - In 56 postoperative patients with primary hyperparathyroidism we analysed
      retrospectively whether a single-sided or minimal invasive operative procedure
      could have been utilized. Additionally the sensitivity of (99m)TC
      Sestamibiscintiscanning and ultrasound of the neck region was assessed. Single
      gland disease was found in 49 patients, 6 patients had primary multiglandular
      disease and one patient revealed a double adenoma. The overall sensitivity of
      (99m)TC-Sestamibiscintiscanning and ultrasound was found to be 78 % and 53 %
      respectively. In 46 patients the operation would have been started minimal
      invasive, in 7 of these patients a conversion to bilateral exploration would have
      been necessary because of four gland hyperplasia, double adenoma or misleading
      preoperative localisation. In 39 patients a successful minimal invasive procedure
      would have been possible. A primary bilateral exploration would have been
      necessary in 10 patients because of either coexisting goiter or questionable
      localisation of the pathological altered gland. Since sensitivity of localisation
      diagnostics is low with regard to multiglandular disease, parathyroid hormone
      should be monitored intraoperatively whenever minimal invasive operative
      procedures are performed.

PMID- 12058307
TI  - [Intraoperative monitoring of intact parathyroid hormone during surgery for
      primary hyperparathyroidism].
AB  - The aim of the present study was to evaluate a new immunometric assay for
      intraoperative parathyroid hormone monitoring. The test was applied in 70
      patients who underwent surgery for primary hyperthyroidism (pHPT) between 6/1999
      and 6/2001. Among these patients, 61 showed a solitary adenoma, eight a
      hyperplasia and one a double adenoma. Intraoperative iPTH samples were taken at
      the beginning of the operation and 5, 10 and 15 min after removal of the
      parathyroid gland. Criterion for a successful operation were a decrease of iPTH
      levels of more than 50 % within 5 min and of more than 60 % within 15 min after
      parathyroidectomy. Following the removal of a solitary adenoma, iPTH levels
      decreased by 63 % (+/- 13 %) after 5 min and by 76 % (+/- 10 %) after 15 min
      respectively. In case of hyperplasia, a significant decrease of iPTH levels was
      not observed until a subtotal parathyroidectomy had been carried out. In the
      present study there were 2 false negative and one false positive results
      corresponding with a sensitivity of 97 % and a specificity of 89 % for prediction
      of a solitary adenoma. In our opinion, intraoperative iPTH monitoring using this
      new assay allows the safe distinction between adenoma and multiglandular disease.
      It represents a valuable adjunct to surgical skill as it permits minimally
      invasive operations for solitary adenomas, and in case of recurrent surgery helps
      to detect the region of interest by selective venous sampling for parathyroid
      hormone.

PMID- 12058309
TI  - [Comment by request from the editors on the contribution: Thoracoscopic video
      assisted talc pleurodesis--an effective method of treatment of malignant pleural
      effusion].

PMID- 12058308
TI  - [Thoracoscopic video-assisted talcum pleurodesis (TTP)--effective treatment of
      malignant pleural effusion].
AB  - INTRODUCTION: Aim of the palliative therapeutic procedure should be a fast,
      efficient and pain free treatment of the malignant pleural effusions. PATIENTS
      AND METHOD: Since 1995 the results of malignant pleural effusions treatment were
      analyzed retrospectively in 46 patients who underwent 51 video-assisted TTP. The
      most frequent origin of malignant pleural effusion was breast cancer, followed by
      bronchial carcinoma. Precondition for video-assisted TTP was the verification of
      a malignant pleural effusion by cytology. RESULTS: Following TTP one patient
      suffered from pneumonia, two recurrent diseases occurred. Four patients died due
      to their severe primary malignancy. Average hospitalization was 8 days (3-55).
      CONCLUSION: Video-assisted TTP is the standard procedure in palliative treatment
      of malignant pleural effusion; the recurrence rate is low and the technique
      minimal invasive.

PMID- 12058310
TI  - [Therapeutic strategy of transgastral stenting in retrogastral abscesses].
AB  - We report on two patients with postinterventional retrogastric abscesses, one as
      a postoperative complication after partial pancreatectomy, one as a complication
      of biliary pancreatitis. In both cases, the abscess cavity could be completely
      drained by EUS-guided endoscopic application of a short "Amsterdam" stent, length
      4 cm, 11.5 Fr. The stents could be removed by endoscopy after an interval of
      several weeks. In suitable cases EUS-guided endoscopic transgastral stenting
      appears to be the therapy of choice for retrogastral abscesses.

PMID- 12058311
TI  - Studies on the anti-inflammatory activity of phytopharmaceuticals prepared from
      Arnica flowers.
AB  - Phytopharmaceuticals prepared from flowerheads of Arnica montana of Spanish
      origin and of the new type "Arbo", which can be easily and economically
      cultivated, were studied for their capability to impair activation of the
      transcription factors NF-kappa B and NF-AT. Both proteins are responsible for the
      transcription of genes encoding various inflammatory mediators. Additionally,
      their influence on the release of the cytokines IL-1 and TNF-alpha were examined.
      The inhibitory activities correlate with their quantitative and qualitative
      content of sesquiterpene lactones (Sls). Moreover, it was shown that the
      inhibitory potency of 11 alpha,13-dihydrohelenalin derivatives being the main Sls
      in the Spanish flowers depend on their esterfication. Compounds with unsaturated
      acyl moieties, such as methacrylate and tiglinate, exhibited a stronger activity
      in the NF-kappa B EMSA as well as in the croton oil ear test in mice than the
      acetate derivative.

PMID- 12058312
TI  - Expression of inducible nitric oxide synthase by alpha-hederin in macrophages.
AB  - alpha-Hederin, a triterpene saponin, is reported to have antitumor activities;
      however, the mechanism underlying its therapeutic effects is not known. In this
      study, we examine the effects of alpha-hederin on the release of nitric oxide
      (NO) and the level of inducible nitric oxide synthase (iNOS) gene expression in
      mouse macrophages. alpha-Hederin elicited a dose-dependent increase in NO
      secretion. Reverse-transcription polymerase chain reaction showed that the
      increased NO secretion was due to an increase in iNOS mRNA. Transient expression
      assays with NF-kappa B binding sites linked to the luciferase gene revealed that
      the increased level of iNOS mRNA induced by alpha-hederin was mediated by the NF
      kappa B transcription factor complex. These results demonstrate that alpha
      hederin stimulates NO release and is able to upregulate iNOS expression through
      NF-kappa B transactivation, which may be a mechanism, whereby alpha-hederin
      elicits its biological effects.

PMID- 12058313
TI  - Cytotoxic action of acetyl-11-keto-beta-boswellic acid (AKBA) on meningioma
      cells.
AB  - Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic
      triterpene isolated from the gum resin exudate of the tree Boswellia serrata
      (frankincense). Because pentacyclic triterpenes have antiproliferative and
      cytotoxic effects against different tumor types, we investigated whether AKBA
      would act in a similar fashion on primary human meningioma cell cultures. Primary
      cell cultures were established from surgically removed meningioma specimens. The
      number of viable cells in the absence/presence of AKBA was determined by the non
      radioactive cell proliferation assay. The activation status of the proliferative
      cell marker, extracellular signal-regulated kinase-1 and -2 (Erk-1 and Erk-2) was
      determined by immunoblotting with the antibody that recognizes the activated form
      of these proteins. Treatment of meningioma cells by AKBA revealed a potent
      cytotoxic activity with half-maximal inhibitory concentrations in the range of 2 
      8 microM. At low micromolar concentrations, AKBA rapidly and potently inhibited
      the phosphorylation of Erk-1/2 and impaired the motility of meningioma cells
      stimulated with platelet-derived growth factor BB. The cytotoxic action of AKBA
      on meningioma cells may be mediated, at least in part, by the inhibition of the
      Erk signal transduction pathway. Because of the central role the Erk pathway
      plays in signal transduction and tumorigenesis, further investigation into the
      potential clinical use for AKBA and related boswellic acids is warranted.

PMID- 12058314
TI  - Hepatoprotective effect of majonoside R2, the major saponin from Vietnamese
      ginseng (Panax vietnamensis).
AB  - The hepatoprotective effect of majonoside R 2 (MR2), the major saponin
      constituent from Vietnamese ginseng ( Panax vietnamensis, Araliaceae), was
      evaluated in vivo on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced
      hepatic apoptosis and subsequent liver failure in mice. Pretreatment of mice with
      MR2 (50 or 10 mg/kg, intraperitoneal) at 12 and 1 h before D-GalN/LPS injection
      significantly inhibited apoptosis and suppressed following hepatic necrosis.
      Importantly, the elevation of serum tumor necrosis factor-alpha (TNF-alpha)
      level, an important mediator for apoptosis in this model, was significantly
      inhibited by MR2 at a dose of 50 mg/kg. On the other hand, MR2 was found to
      protect primary cultured mouse hepatocytes from cell death by inhibiting
      apoptosis induced by D-GalN/TNF-alpha in vitro, as evidenced by DNA fragmentation
      analysis. These findings suggested that MR2 may have protected the hepatocytes
      from apoptosis via an inhibition of TNF-alpha production by activated macrophages
      and a direct inhibition of apoptosis induced by TNF-alpha.

PMID- 12058315
TI  - Hepatoprotective phenylpropanoids from Scrophularia buergeriana roots against
      CCl(4)-induced toxicity: action mechanism and structure-activity relationship.
AB  - Phenylpropanoids isolated from the roots of Scrophularia buergeriana MIQ.
      (Scrophulariaceae) protected primary cultures of rat hepatocytes from toxicity
      induced by carbon tetrachloride (CCl(4) ). In this report, we show that two of
      these phenylpropanoids, 4-O-E- p-methoxycinnamoyl-alpha-L-rhamnopyranoside ester
      ( 1) and p-methoxycinnamic acid ( 3) have significant hepatoprotective activity;
      another phenylpropanoid used for comparison, isoferulic acid ( 11), was equally
      active. To determine the mechanism(s) by which these three phenylpropanoids
      exerted their hepatoprotective activity, we measured activities of enzymes
      involved in the glutathione (GSH) redox system and assayed the level of hepatic
      mitochondrial GSH. The GSH levels in primary cultures of rat hepatocytes were
      significantly reduced with CCl(4) insult, but were significantly preserved by the
      treatment with these three phenylpropanoids. The activities of glutathione
      disulfide reductase and glutathione-S-transferase which normally decrease in
      CCl(4) -injured rat hepatocytes were significantly preserved by the treatment
      with these three phenylpropanoids. In addition, in CCl(4) -injured rat
      hepatocytes, the increased formation of malondialdehyde, a byproduct of lipid
      peroxidation, was reduced by the treatment with these phenylpropanoids. We
      determined the essential structural moiety within these three phenylpropanoids
      needed to exert hepatoprotective activity. The alpha,beta-unsaturated ester
      moiety seemed to be essential for exerting hepatoprotective activity.

PMID- 12058317
TI  - In vitro antimycobacterial and antilegionella activity of licochalcone A from
      Chinese licorice roots.
AB  - Licochalcone A, extracted and purified from Chinese licorice roots, showed in
      vitro inhibitory effect on human pathogenic Mycobacteria species and Legionella
      species. M. tuberculosis, M. bovis and BCG were inhibited by < 20 mg/l
      licochalcone A, whereas all non- M. tuberculosis complex species were resistant
      to > 20 mg/l Legionella pneumophila (serogroups 1 - 7) and L. bozemanii, L.
      dumoffii, L. feelei, L. longbeacheae and L. wadsworthii were inhibited by
      licochalcone A 1 - 4 mg/l, whereas L. gormanii and L. micdadei were inhibited by
      licochalcone A 500 - 1000 mg/l. These data indicate that licochalcone A might be
      of interest as a new class of antibacterial drug in the treatment of severe lung
      infections.

PMID- 12058316
TI  - Mechanism of endothelium-dependent vasodilation induced by a proanthocyanidin
      rich fraction from Ouratea semiserrata.
AB  - The vasodilator effects of Ouratea semiserrata stem hydroethanolic extract (OSE)
      and its ethyl acetate fraction (OSR) were evaluated in endothelium-intact aortic
      rings. OSR produced a more potent vasodilatation (IC(50) = 3.5 +/- 0.8 microg/ml)
      than OSE (IC(50) > 30 microg/ml). OSR also presented a higher content of total
      proanthocyanidins (21.8 +/- 1.5 %) in comparison to OSE (6.5 +/- 0.4 %),
      suggesting that compounds of this class play a role in the vasorelaxing activity.
      The vasodilatation mechanism of OSR was further investigated. In endothelium
      intact aortic rings, its vasorelaxing effect was completely abolished by L-NAME
      (300 microM), a nitric oxide (NO) synthase inhibitor, but not by a muscarinic
      antagonist (atropine, 1 microM) nor by a cyclo-oxygenase inhibitor (indomethacin,
      10 microM). The OSR vasodilator effect was completely abolished in endothelium
      denuded vessels. Furthermore, OSR did not change the vasodilatation produced by
      SIN-1, an NO donor, in endothelium-denuded vessels. These findings led us to
      conclude that OSR, a proanthocyanidin rich fraction of O. semiserrata, induces
      vasodilatation by a mechanism dependent on endothelium-derived factors, likely
      NO.

PMID- 12058318
TI  - Efficient paclitaxel production using protoplasts isolated from cultured cells of
      Taxus cuspidata.
AB  - Efficient isolation of protoplasts from Taxus cuspidata cultured cells,
      localization of paclitaxel in the cultured cells, and efficient production of
      paclitaxel by protoplasts were studied. Hemicellulase, potassium citric acid
      solution, and degassing treatments were effective in increasing the yield of
      protoplasts isolated from T. cuspidata cultured cells. Protoplasts yields (3.2 -
      6.4 x 10(6) number/g-fresh weight cells) were achieved by combining the various
      treatments with specific culture and cell phases. It was found that about 30% and
      35% of paclitaxel in the cells was located in cell walls and/or between the cell
      wall and cell membrane (CW) of suspension cells in the growth phase and in the
      stationary phase, respectively. About 30% and 43% of paclitaxel in the cells was
      located in CW of the cells grown in solid culture in growth phase and in the
      stationary phase, respectively. In comparison with cell suspension culture,
      protoplasts in a static culture and the protoplasts immobilized in agarose gel in
      shaking culture resulted to about 6 times increase in the extracellular
      paclitaxel accumulation.

PMID- 12058320
TI  - New oxypregnane glycosides from Caralluma penicillata.
AB  - The ether fraction of the defatted ethanol extract of the aerial parts of
      Caralluma penicillata (defl) M. E. Br. (Asclepiadaceae) yielded four new
      oxypregnane glycosides, penicillosides D-G. The structures of the isolated
      compounds were established by different spectroscopic methods.

PMID- 12058319
TI  - Cytotoxic terpenoid and immunosuppressive phenolic glycosides from the root bark
      of Dictamnus dasycarpus.
AB  - Five new compounds, two degraded terpene glycosides, dasycarpusides A and B (1,
      2), and three phenolic glycosides, 2-methoxy-4-hydroxymethylphenol 1-O-alpha
      rhamnopyranosyl-(1"-->6')- beta-glucopyranoside ( 3), 2-methoxy-4-acetylphenol 1
      O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside (4), and 2-methoxy-4-(8
      hydroxyethyl)-phenol 1-O-alpha-rhamnopyranosyl-(1"-->6')-beta-glucopyranoside
      (5), were isolated from the water-soluble constituents of the root bark of
      Dictamnus dasycarpus Turcz.(Rutaceae). Their structures were elucidated by
      spectroscopic analysis and chemical evidence. Moreover, it was found that
      dasycarpuside A (1) showed weak cytotoxic activity against A-549 (human lung
      adenocarcinoma) cell line, while 4 and 5 showed more remarkable activity of
      inhibiting the proliferation of T-cells in vitro.

PMID- 12058321
TI  - Isolation and structure elucidation of a new indole alkaloid from Rauvolfia
      serpentina hairy root culture: the first naturally occurring alkaloid of the
      raumacline group.
AB  - A new monoterpenoid indole alkaloid, 10-hydroxy- N(alpha)-demethyl-19,20
      dehydroraumacline ( 1), was isolated as a mixture of E- and Z-isomers from hairy
      root culture of Rauvolfia serpentina Benth. ex Kurz (Apocynaceae) and the
      structure was determined by 1D and 2D NMR analyses. The new indole alkaloid
      represents the first naturally occurring alkaloid of the raumacline group and its
      putative biosynthetical pathway is discussed.

PMID- 12058322
TI  - Capillary electrophoresis determination of biflavanones from Garcinia kola in
      three traditional African medicinal formulations.
AB  - A rapid capillary electrophoresis (CE) method for the quantification of four
      biologically active biflavanones present in three different traditional African
      medicinal preparations from the seeds of Garcinia kola was developed. The four
      biflavanones of interest (GB1, GB2 and GB1-glycoside and kolaflavanone) were
      quantified in a traditional tea preparation, and two commercially available
      ethanolic formulations. The optimum separation conditions consisted of a 100 mM
      borate, pH 9.5 running buffer, which gave baseline resolution of all four
      components in less than 12 minutes. Linear calibration ranges for each component
      were between 2.5 and 1000 microg/mL. Limits of detection for the biflavanones
      quantified in this study were between 3 and 6 microg/mL. The "fingerprint" of the
      biflavanones in the aqueous tea and two ethanolic formulations was found to be
      similar, however concentrations of the four biflavanones were up to 50 fold
      higher in the ethanolic preparations. The major component in all three
      formulations was GB1.

PMID- 12058323
TI  - Interference of plant extracts, phytoestrogens and antioxidants with the MTT
      tetrazolium assay.
AB  - The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay is a
      widely used screening method to measure cell viability and proliferation. When
      testing the effects of kaempferol on breast cancer cell number (crystal violet
      staining) and viability (MTT tetrazolium assay) conflicting results were
      obtained. Cell number decreased but MTT formazan formation increased, suggesting
      a direct interaction of kaempferol with the MTT tetrazolium reduction. Direct
      reductive potential was observed in a cell-free system for the presumptive
      phytoestrogens kaempferol and resveratrol, and extracts of Hypericum perforatum
      L. and Cimicifuga racemosa L. All agents led to instantaneous dark blue formazan
      formation in the absence of cells. Additionally, antioxidants such as ascorbic
      acid, vitamin E and N-acetylcysteine interfered with the MTT tetrazolium assay.
      When MCF7 and HS578 cells treated with kaempferol were washed before addition of
      MTT tetrazolium, the direct reduction of dye was reduced significantly. These
      results indicate that the MTT tetrazolium assay may lead to false positive
      results when testing natural compounds with intrinsic reductive potential.

PMID- 12058324
TI  - Estrogenic activity of the phytoestrogens naringenin, 6-(1,1
      dimethylallyl)naringenin and 8-prenylnaringenin.
AB  - Chemically synthesized naringenin derivatives, identical to natural occurring
      compounds, were tested for their estrogenic activity using two independent
      estrogen screening assays. Using a yeast based estrogen receptor assay, strong
      estrogenic activities were demonstrated for 6-(1,1-dimethylallyl)naringenin and 8
      prenylnaringenin, while the parent compound naringenin did not show recognizable
      estrogenic activity. In MVLN cells, a bioluminescent MCF-7-derived cell line, the
      estrogenic activity of 8-prenylnaringenin and 6-(1,1-dimethylallyl)naringenin was
      detected at concentrations of 10(-6) M and 5 x 10(-6) M respectively. Naringenin
      demonstrated estrogenic activity but only at a concentration of 10(-5) M. These
      estrogenic effects are mediated by the ER, as the antiestrogen 4-hydroxytamoxifen
      inhibited these activities. In summary, this study provides the further
      confirmation that 8-prenylnaringenin demonstrates high estrogenic activity, and
      demonstrated for the first time for 6-(1,1-dimethylallyl)naringenin a reasonable
      high estrogenic activity, while naringenin exhibit low or no estrogenic activity.

PMID- 12058325
TI  - Characterization of the bactericidal activity of the natural diterpene kaurenoic
      acid.
AB  - Kaurenoic acid is a diterpene with selective antibacterial activity against Gram
      positive bacteria. The compound is bacteriolytic for Bacillus cereus. This
      activity was only partially affected by the composition and pH of the culture
      medium. Loss of the ability to retain the Gram stain and morphological
      alterations were produced in B. cereus cells exposed to kaurenoic acid. On the
      other hand, LPS mutants of Salmonella typhi were resistant to the compound, but
      spheroplasts of Escherichia coli became more sensitive to kaurenoic acid.

PMID- 12058326
TI  - Antiproliferative amaryllidaceae alkaloids isolated from the bulbs of Sprekelia
      formosissima and Hymenocallis x festalis.
AB  - Seven alkaloids were isolated from Sprekelia formosissima, and five from
      Hymenocallis x festalis. Tazettine, lycorine, haemanthidine and haemanthamine
      were evaluated for antiproliferative and multidrug resistance (mdr) reversing
      activity on mouse lymphoma cells. Lycorine, haemanthidine and haemanthamine
      displayed pronounced cell growth inhibitory activities against both drug
      sensitive and drug-resistant cell lines, but did not significantly inhibit mdr-1
      p-glycoprotein. Thus, the tested alkaloids are apparently not substrates for the
      mdr efflux pump. Assays for interactions with DNA and RNA revealed that the
      antiproliferative effects of lycorine and haemanthamine result from their complex
      formation with RNA.

PMID- 12058327
TI  - Inhibition of HIV-1 integrase by galloyl glucoses from Terminalia chebula and
      flavonol glycoside gallates from Euphorbia pekinensis.
AB  - The bioassay-directed isolation of Terminalia chebula fruits afforded four human
      immunodeficiency virus type 1 (HIV-1) integrase inhibitors, gallic acid ( 1) and
      three galloyl glucoses ( 2 - 4). In addition, four flavonol glycoside gallates (
      5 - 8) from Euphorbia pekinensis containing the galloyl moiety also showed the
      inhibitory activity at a level comparable to those of 2 - 4. By comparison with
      the activities of the compounds not bearing this moiety, it is proposed that the
      galloyl moiety plays a major role for inhibition against the 3'-processing of HIV
      1 integrase of these compounds.

PMID- 12058328
TI  - Effect of the essential oil from the flowers of Magnolia sieboldii on the
      lipopolysaccharide-induced production of nitric oxide and prostaglandin E2 by rat
      peritoneal macrophages.
AB  - The essential oil from the flowers of Magnolia sieboldii was tested for its
      effects on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and
      prostaglandin E(2) (PGE(2)) by rat peritoneal macrophages. It was shown to induce
      the production of NO and PGE 2 in a concentration-dependent manner (3 - 30
      microg/ml). Gas chromatography (GC) and gas chromatography/mass spectrometry
      (GC/MS) led to the identification of sixty compounds, of which beta-elemene (18.0
      %), alpha-terpinene (14.83 %) and beta-myrcene (12.72 %) were the major
      constituents. Among these three compounds, alpha-terpinene was found to be the
      most effective one with inhibitory activity on NO and PGE(2) production by LPS
      stimulated rat peritoneal macrophages.

PMID- 12058329
TI  - Furocoumarins from Angelica dahurica with hepatoprotective activity on tacrine
      induced cytotoxicity in Hep G2 cells.
AB  - Fractionation of the MeOH extract of Angelica dahurica Benth et Hook resulted in
      the isolation of six furocoumarins, imperatorin (1), isoimperatorin (2), (+/-)
      byakangelicol (3), (+)-oxypeucedanin (4), (+)-byakangelicin (5), and (+)-aviprin
      (6). Among these, compounds 1 and 5 exhibited strong hepatoprotective activities,
      displaying EC(50) values of 36.6 +/- 0.98 and 47.9 +/- 4.6 microM, respectively.
      Compounds 3 and 4 showed moderate activities with EC(50) values of 112.7 +/- 5.35
      and 286.7 +/- 6.36 microM, respectively. Silybin as a positive control showed the
      EC(50) value with 69.0 +/- 3.4 microM. Comparison of hepatoprotective activities
      for six furocoumarins 1 - 6 suggested that oxy-substitution at the C-9 position
      increased the hepatoprotective activity.

PMID- 12058330
TI  - The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic
      actions.
AB  - A plant mixture containing extracts of Nigella sativa possesses blood glucose
      lowering effects, but the direct antidiabetic effect of Nigella sativa is not yet
      established. Therefore, the effect of Nigella sativa oil (NSO) on blood glucose
      concentrations was studied in streptozotocin diabetic rats. In addition, the
      effect of NSO, nigellone and thymoquinone were studied on insulin secretion of
      isolated rat pancreatic islets in the presence of 3, 5.6 or 11.1 mM glucose. NSO
      significantly lowered blood glucose concentrations in diabetic rats after 2, 4
      and 6 weeks. The blood lowering effect of NSO was, however, not paralleled by a
      stimulation of insulin release in the presence of NSO, nigellone or thymoquinone.
      The data indicate that the hypoglycemic effect of NSO may be mediated by
      extrapancreatic actions rather than by stimulated insulin release.

PMID- 12058331
TI  - Inhibitory effect of xanthomicrol and 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14Z
      dehydrocativic acid from Brickellia paniculata on the contractility of guinea-pig
      ileum.
AB  - Chemical fractionation of Brickellia paniculata methanolic extract by monitoring
      its inhibitory effect on K(+)-induced contraction in guinea-pig ileum in vitro
      led to the isolation of 5,4'-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol) and
      the labdane-diterpene 3 alpha-angeloyloxy-2 alpha-hydroxy-13,14 Z-dehydrocativic
      acid (AAHDD). Both compounds inhibited the tonic contraction the effect being
      highly potent when a mixture in a proportion of 3 : 1 (xanthomicrol/AAHDD) was
      assayed. The phasic component of the contractile response with K(+) was also
      reduced by the compounds. Xanthomicrol depressed the spasms induced with ACh,
      Hist, and BaCl(2) and its effect on Ca (2+) concentration-response curve showed a
      type of non-surmountable calcium blocking action; unlike the flavonoid, AAHDD
      produced a parallel rightward shift of the concentration-response curve to
      calcium, suggesting a competitive antagonism with an estimated pA(2) of 4.66.
      Obtained results support, in part, the popular use of B. paniculata as a
      spasmolytic remedy.

PMID- 12058332
TI  - Transport of alkamides from Echinacea species through Caco-2 monolayers.
AB  - To gain more insights into the human intestinal absorption of alkamides from
      Echinacea species, transport studies were performed with the human adenocarcinoma
      colonic cell line Caco-2 (ATCC) as a model to assess the epithelial transport of
      dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2). 30 minutes
      after apical loading of 25 microg/ml 1/ 2, about 15 % of these alkamides were
      detectable on the basolateral side. Close monitoring of the transport during 6
      hours revealed a nearly complete transport to the basolateral side after 4 hours
      and no significant metabolism was observable. Transport experiments performed at
      4 degrees C showed only a slight decrease in transport, which is a strong hint
      that dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2) cross
      biological membranes by passive diffusion. Nearly the same results were obtained
      after preincubation of the Caco-2 cells with lipopolysaccharides (LPS) or phorbol
      12-myristate-13-acetate (PMA) to mimic an inflammatory status. These results
      support the assumption that the alkamides can be easily transported from the
      intestinum and hence may contribute to the in vivo effects of Echinacea
      preparations.

PMID- 12058333
TI  - Effect of drought stress on the yield and composition of volatile oils of drought
      tolerant and non-drought-tolerant clones of Tagetes minuta.
AB  - A drought-tolerant clone of Tagetes minuta L. (Asteraceae) was selected in vitro
      on a medium containing 60 mM mannitol. In the greenhouse, a decrease in soil
      field capacity (FC) from 100 to 40 % reduced oil yield by 49, 71 and 71 % for
      drought-tolerant, non-drought tolerant cloned and seed-grown plants,
      respectively. In soil at 40 % FC, the drought-tolerant clone had the highest leaf
      dry weight and oil yield. At 100 % FC, there was no significant difference in
      leaf dry weight, but the drought-tolerant clone had a significantly higher
      percentage oil content and yield than seed-grown plants. The main components of
      the oil were monoterpenes of which trans- and cis-tagetone together were 52.3 % -
      64.2 %. Drought significantly altered the content of some oil components.

PMID- 12058334
TI  - Jasmonic acid stimulates taxane production in cell suspension culture of yew
      (Taxus x media).
AB  - Cell lines of Taxus x media Rehd. were established via embryo and callus culture
      and grown on B5 medium containing 10 microM 2,4-D and 1 microM kinetin. Jasmonic
      acid (JA) was used to elicit taxane synthesis in a selected yew cell line. 100
      microM JA was added 7 days after subculture. JA strongly increased taxane content
      in the cells and in the medium. At the time of the highest amount in elicited
      cultures, the enhancement of paclitaxel production was 19-fold and 4-fold in the
      cells and medium, respectively, compared to controls (non-elicited cultures). The
      time course of taxane accumulation in the cells and in the medium and the release
      of taxanes into the medium were not changed after JA elicitation.

PMID- 12058335
TI  - Taibaijaponicains C and D: two new diterpenoids from Isodon japonica.
AB  - Two new C-20-oxygenated ent-kaurene diterpenoids, taibaijaponicains C and D,
      together with five known compounds, were isolated from the ethanol extract of the
      leaves and branches of Isodon japonica (Burm. f.) Hara. The structures of new
      compounds were elucidated as 1 alpha-aectoxy-7 beta,12 beta,15 alpha-trihydroxy
      16 alpha-hydroxymethyl-7,20-epoxy- ent-kaurane and 1 alpha-acetoxy-2 beta,3
      alpha,6 beta,7 beta,12 beta-pentahydroxy-7,20;19,20-diepoxy- ent-kaur-16-en-15
      one, respectively, on the basis of detailed spectroscopic analysis.

PMID- 12058337
TI  - 50 years of the Institute of Experimental Endocrinology of the Charite (Humboldt
      University, Berlin) -- the way from Aschheim's laboratory of the 2nd Department
      of Obstetrics & Gynaecology to a research institute.
AB  - The aim of this article is firstly to elucidate the historical roots which
      preceded the foundation of the first Institute of Experimental Endocrinology in
      Germany and secondly to illustrate the special development of this Institute with
      its ups and downs within the context of German history.

PMID- 12058336
TI  - Pyrrolizidine alkaloids in Pulmonaria obscura.
AB  - Leaves, roots and rhizomes, and inflorescenses of Pulmonaria obscura from two
      localities and of two different growth forms within one site were analyzed by GC
      MS for their content in pyrrolizidine alkaloids (PAs). In roots and rhizomes PAs
      of the lycopsamine type typical for the Boraginaceae could be detected, e. g.
      intermedine, lycopsamine, and their O(7)-derivatives. The total PA concentrations
      in roots and rhizomes lay between 0.026 and 0.158 mg/g dry weight. In leaves and
      inflorescenses, on the other hand, only trace amounts of PAs (below 0.4 ng/mg dry
      weight) could be detected. No significant differences in total concentration of
      PAs could be found between the two sites.

PMID- 12058338
TI  - Determination of the modulus of elasticity of bone material by an acoustical
      approach at the forearm distinguishes women with and without vertebral fractures
      independent of bone mineral density.
AB  - The modulus of elasticity is a parameter characterizing fracture stability of
      bone independent of bone mineral density. Measurement of acoustical properties of
      the forearm by determination of the resonant frequency of the ulna in
      longitudinal direction as a function of sound transmission velocity after
      adjustment of the measuring result by ulna length yields information about the
      modulus of elasticity. It was the aim of this study to investigate whether this
      parameter may distinguish between subjects with and without vertebral fractures
      independent of bone mineral density. Fifty females (61.1 +/- 9.1 years) were
      enrolled into the study, 25 with, and 25 age-matched without prevalent
      osteoporotic vertebral fracture(s). Especially low bone mineral density was not
      considered an exclusion criteria for enrollment into the control group. Resonant
      frequency of the ulna multiplied by ulna length was significantly lower in the
      group with prevalent fractures (53.6 +/- 6.8 m/s versus 56.8 +/- 5.2 m/s) after
      adjustment for age and after additional adjustment for forearm bone mineral
      density. Linear regression analysis showed complete independence of the
      acoustical parameter from bone mineral density. This study demonstrates that the
      modulus of elasticity of bone material is an independent risk factor for
      osteoporotic fractures. Acoustical measurement at the forearm by analyzing the
      resonant frequency of the ulna and correcting it by ulna length as geometrical
      parameter is capable of determining the modulus of elasticity in vivo.

PMID- 12058339
TI  - Thyroid hormone receptors and type I iodothyronine 5'-deiodinase activity of
      human thyroid toxic adenomas and benign cold nodules.
AB  - The majority of thyroid adenomas are of clonal origin. In a subset of toxic
      adenomas (TAs) and cold nodules (CNs) activating mutations in the thyrotropin
      (TSH) receptor or G s -alpha gene may explain the altered functions in these
      benign tumours. The present study was undertaken to investigate the status of
      functional thyroid hormone receptors, major thyroid hormone signal mediators, in
      both the human TAs and CNs in comparison with a normal thyroid tissue from the
      same patient. Electrophoretic mobility shift assays using a DR4 ("direct repeats"
      4), a thyroid hormone responsive element (TRE) of human type I iodothyronine 5'
      deiodinase demonstrated the DNA-binding of thyroid hormone receptors (TRs) in
      thyroid tissue nuclear extracts. A significant increase (p < 0.05) in the
      functional binding properties of TRs to the DR4 thyroid hormone responsive
      element was found in TAs when compared to normal thyroid tissue. Contrary, a
      marked diminution in the TR-TRE complex formation was found in CNs in comparison
      with normal thyroid tissue. In addition, functional activity of the iodothyronine
      5'-deiodinase (5'DI) was analyzed in benign tumours, thyroid TAs and CNs in
      comparison with that of normal thyroid tissue. A significantly increased (p <
      0.01) activity of 5'DI was demonstrated in TAs, and in contrast, decreased values
      of the enzyme activity were found in CNs when compared to a normal tissue. From
      the data it is suggested that both the status of TR-TRE complex formation and the
      activity of the 5'DI may be altered in benign tumours of human thyroid gland.

PMID- 12058340
TI  - Postpartum thyroiditis in India: prevalence of postpartum thyroiditis in Kashmir
      Valley of Indian sub-continent.
AB  - Various studies have reported a spectrum of thyroid dysfunction in the postpartum
      period. Postpartum thyroiditis is a syndrome of thyroid dysfunction that occurs
      in the first year after parturition. Prevalence of postpartum thyroiditis has
      been reported to vary from 3 to 6 percent in different regions of the world.
      Kashmir Valley is inhabited by a relatively homogeneous racial group and the
      Valley has been documented to have significant iodine deficiency. We studied the
      prevalence and pattern of postpartum thyroiditis in an urban region of this
      Valley. 120 women were registered within first month of postpartum period for the
      study along with one hundred controls. Of these 120 women, 104 reported for
      follow-up at 3 months postpartum and 106 reported for follow-up at 6 months
      postpartum. Initial and subsequent clinical details at follow-up were recorded on
      a pre-determined questionnaire. Overall, postpartum thyroiditis (PPT) was seen in
      8 (7%) study subjects. Of these 8 patients with PPT, 4 had biochemical evidence
      of thyrotoxicosis at first month, 3 developed biochemical thyrotoxicosis at 3
      month follow-up while as one study subject developed thyrotoxicosis at 6 months.
      Most of these subjects were antithyroid antibodies (anti-microsomal and anti
      thyroglobulin) positive. We conclude that iodine deficient status of the
      community doesn't seem to influence the incidence of PPT.

PMID- 12058341
TI  - Effects of basic fibroblast growth factor (FGF-2) on proliferation of human skin
      fibroblasts in type II diabetes mellitus.
AB  - Skin fibroblasts from patients with diabetes mellitus display abnormalities in
      cell proliferation. The use of exogenous growth factors on diabetic wounds has
      been found to stimulate fibroblast proliferation and facilitate wound healing.
      However, the results of application of FGF-2 alone to diabetic wounds in clinical
      trials have been disappointing. The objective of this experiment was to study the
      effects of FGF-2 and media supplements on in vitro proliferation of skin
      fibroblasts from patients with type II diabetes and nondiabetic controls, and to
      evaluate the association between fibroblast proliferation and cAMP production.
      Fibroblast cell lines (n = 5 from diabetic and n = 5 from control individuals)
      were cultured in DMEM + 20% FBS for 7 days. Cells were then counted, plated into
      24-well plates at a concentration of 2 x 10(4) cells/well and incubated for 24 h
      in DMEM with serum. The next day, medium was changed to serum-free DMEM alone or
      DMEM with supplements (albumin, transferrin, insulin and hydrocortisone). Cells
      were cultured in the presence or absence of varying doses of FGF-2 (0, 0.3, 1, 3,
      10 and 30 ng/ml) for 72 hrs then counted and medium was collected for cAMP
      radioimmunoassay. The doubling time for cell number tended to be greater (p <
      0.2) for diabetic fibroblasts than for control fibroblasts. The addition of
      supplements to the medium reduced (p < 0.05) the doubling time for both
      fibroblast types. FGF-2 stimulated (p < 0.05) proliferation of diabetic
      fibroblasts only in medium containing supplements. In contrast, FGF-2 stimulated
      proliferation of control fibroblasts in medium with or without supplements. The
      maximal effects of FGF-2 on fibroblast proliferation were greater (p < 0.02) in
      medium with supplements than in medium without supplements. The K(D) of FGF-2 for
      fibroblast proliferation was greater (p < 0.06) for diabetic than for control
      fibroblasts, and lower (p < 0.02) for medium with supplements than for medium
      without supplements. Fibroblasts from patients with diabetes mellitus produced
      more (p < 0.05) cAMP than control fibroblasts. These results demonstrate that FGF
      2 requires the presence of supplements to enhance proliferation of fibroblasts
      from patients with type II diabetes mellitus. In addition, fibroblasts from
      diabetic patients showed a greater K(D) for FGF-2 in terms of cell proliferation.
      These data suggest a defective FGF receptor or down-regulation of the FGF
      receptor-mediated cascade that leads to cell proliferation. Identifying methods
      of reducing the K(D) of FGF-2 in stimulating the proliferation of diabetic
      fibroblasts may improve the clinical response of diabetic wounds to FGF-2.

PMID- 12058342
TI  - Influence of simvastatin on LDL-subtypes in patients with heterozygous familial
      hypercholesterolemia and in patients with diabetes mellitus and mixed
      hyperlipoproteinemia.
AB  - This study evaluates the influence of simvastatin on lipid concentrations and on
      LDL-subtype distribution in patients with heterozygous familial
      hypercholesterolemia and in patients with type 2 diabetes and mixed
      hyperlipoproteinemia. Nine patients with familial hypercholesterolemia (LDL
      cholesterol: 7.1 +/- 1.1 mmol/L, triglycerides: 1.3 +/- 0.4 mmol/L) and 8
      patients with type 2 diabetes mellitus and mixed hyperlipoproteinemia (HbA1c 6.8
      +/- 1.1%, LDL-cholesterol: 4.8 +/- 0.7 mmol/L, triglycerides: 2.5 +/- 1.1 mmol/L)
      were examined. Cholesterol concentration was determined in 7 LDL-subfractions
      isolated by density gradient ultracentrifugation before and during simvastatin
      treatment (10-20 mg/d, 4 weeks). Simvastatin decreased LDL-cholesterol (-34%/
      30%, all p < 0.05) and triglycerides (-2%, n.s./-25%, p < 0.05), but had little
      effect on HDL-cholesterol (+7%/+2%, n.s.) in patients with familial
      hypercholesterolemia and diabetes mellitus, respectively. In both groups a
      significant reduction of cholesterol in each LDL-subfraction was observed. Large
      buoyant (LDL-1, LDL-2) and intermediate-dense (LDL-3, LDL-4) LDL were reduced
      more than small-dense (LDL-5-LDL-7) LDL-subtypes (-36%/-38%/-23%, respectively)
      in patients with familial hypercholesterolemia, while in diabetic patients
      cholesterol reduction was uniform in all LDL-subtypes (-29%/-27%/-31%,
      respectively). Simvastatin decreases cholesterol concentration in all LDL
      subfractions in patients with familial hypercholesterolemia and in patients with
      diabetes mellitus with mixed hyperlipoproteinemia. However, the relative
      reduction of individual LDL-subtypes differed between both groups. This suggests
      that the effect of simvastatin on LDL-subtype distribution depends on the type of
      underlying hyperlipoproteinemia.

PMID- 12058343
TI  - Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery
      following tumor surgery.
AB  - A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid
      is reported. A 61-year-old woman presented with typical symptoms and signs of
      acromegaly for at least 10 years. She suffered from recurrent pneumonias, but
      repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The
      diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown
      an enlarged pituitary gland without focal lesions together with a cerebral
      meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was
      confirmed by histology carried out after bronchoscopy and tumor excision. We
      observed partial suppression of GH secretion following short-term oral
      bromocriptine administration in this patient. Surgical removal of the carcinoid
      tumor resulted in a complete clinical, hormonal and radiological cure of
      acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial
      carcinoid differs from others described in the literature by an atypical large
      tumor size, the suppression of elevated GH secretion by oral bromocriptine and a
      concomitant meningioma.

PMID- 12058344
TI  - Parental genotypes in the risk of a complex disease.
AB  - Our understanding of the genetic etiology of complex disorders is still elusive.
      According to the common-variant/common-disease hypothesis, frequent functional
      polymorphisms are the best candidates for disease-susceptibility alleles.
      Implicitly, we also assume that disease-susceptibility alleles are preferentially
      transmitted from parents to the affected offspring and that this effect can be
      captured by the transmission/disequilibrium test (TDT). However, our study of
      genetic predisposition to childhood acute lymphoblastic leukemia suggests that a
      focus on the patient's genotype might, in certain instances, be misleading. Our
      results indicate that, at least at some loci, parental genetics might be of
      primary importance in predicting the risk of cancer in this pediatric model of a
      complex disease. Consequently, in addition to TDT, other complementary strategies
      will need to be simultaneously applied to dissect genetic predisposition to
      complex disorders.

PMID- 12058345
TI  - Presence of large deletions in kindreds with autism.
AB  - Autism is caused, in part, by inheritance of multiple interacting susceptibility
      alleles. To identify these inherited factors, linkage analysis of multiplex
      families is being performed on a sample of 105 families with two or more affected
      sibs. Segregation patterns of short tandem repeat polymorphic markers from four
      chromosomes revealed null alleles at four marker sites in 12 families that were
      the result of deletions ranging in size from 5 to >260 kb. In one family, a
      deletion at marker D7S630 was complex, with two segments deleted (37 kb and 18
      kb) and two retained (2,836 bp and 38 bp). Three families had deletions at
      D7S517, with each family having a different deletion (96 kb, 183 kb, and >69 kb).
      Another three families had deletions at D8S264, again with each family having a
      different deletion, ranging in size from <5.9 kb to >260 kb. At a fourth marker,
      D8S272, a 192-kb deletion was found in five families. Unrelated subjects and
      additional families without autism were screened for deletions at these four
      sites. Families screened included 40 families from Centre d'Etude du
      Polymorphisme Humaine and 28 families affected with learning disabilities.
      Unrelated samples were 299 elderly control subjects, 121 younger control
      subjects, and 248 subjects with Alzheimer disease. The deletion allele at D8S272
      was found in all populations screened. For the other three sites, no additional
      deletions were identified in any of the groups without autism. Thus, these
      deletions appear to be specific to autism kindreds and are potential autism
      susceptibility alleles. An alternative hypothesis is that autism-susceptibility
      alleles elsewhere cause the deletions detected here, possibly by inducing errors
      during meiosis.

PMID- 12058346
TI  - Evidence that Griscelli syndrome with neurological involvement is caused by
      mutations in RAB27A, not MYO5A.
AB  - Griscelli syndrome (GS), a rare autosomal recessive disorder, is characterized by
      partial albinism, along with immunologic abnormalities or severe neurological
      impairment or both. Mutations in one of two different genes on chromosome 15q can
      cause the different subtypes of GS. Most patients with GS display the
      hemophagocytic syndrome and have mutations in RAB27A, which codes for a small
      GTPase. Two patients with neurological involvement have mutations in MYO5A, which
      codes for an actin-based molecular motor. The RAB27A and MYO5A gene products
      interact with each other and function in vesicle trafficking. We report the
      molecular basis of GS in a Muslim Arab kindred whose members have extremely
      variable neurological involvement, along with the hemophagocytic syndrome and
      immunologic abnormalities. The patients have normal MYO5A genes but exhibit a
      homozygous 67.5-kb deletion that eliminates RAB27A mRNA and
      immunocytofluorescence-detectable protein. We also describe the molecular
      organization of RAB27A and a multiplex polymerase chain reaction assay for the
      founder deletion in this kindred. Finally, we propose that all patients with GS
      have RAB27A mutations and immunologic abnormalities that sometimes result in
      secondary neurological involvement. The two patients described elsewhere who have
      MYO5A mutations and neurological complications but no immunologic defects may not
      have GS but instead may have Elejalde syndrome, a condition characterized by mild
      hypopigmentation and severe, primary neurological abnormalities.

PMID- 12058347
TI  - Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters
      mediate the recurrent t(4;8)(p16;p23) translocation.
AB  - The t(4;8)(p16;p23) translocation, in either the balanced form or the unbalanced
      form, has been reported several times. Taking into consideration the fact that
      this translocation may be undetected in routine cytogenetics, we find that it may
      be the most frequent translocation after t(11q;22q), which is the most common
      reciprocal translocation in humans. Case subjects with der(4) have the Wolf
      Hirschhorn syndrome, whereas case subjects with der(8) show a milder spectrum of
      dysmorphic features. Two pairs of the many olfactory receptor (OR)-gene clusters
      are located close to each other, on both 4p16 and 8p23. Previously, we
      demonstrated that an inversion polymorphism of the OR region at 8p23 plays a
      crucial role in the generation of chromosomal imbalances through unusual meiotic
      exchanges. These findings prompted us to investigate whether OR-related inversion
      polymorphisms at 4p16 and 8p23 might also be involved in the origin of the
      t(4;8)(p16;p23) translocation. In seven case subjects (five of whom both
      represented de novo cases and were of maternal origin), including individuals
      with unbalanced and balanced translocations, we demonstrated that the breakpoints
      fell within the 4p and 8p OR-gene clusters. FISH experiments with appropriate
      bacterial-artificial-chromosome probes detected heterozygous submicroscopic
      inversions of both 4p and 8p regions in all the five mothers of the de novo case
      subjects. Heterozygous inversions on 4p16 and 8p23 were detected in 12.5% and 26%
      of control subjects, respectively, whereas 2.5% of them were scored as doubly
      heterozygous. These novel data emphasize the importance of segmental duplications
      and large-scale genomic polymorphisms in the evolution and pathology of the human
      genome.

PMID- 12058348
TI  - Grouping of multiple-lentigines/LEOPARD and Noonan syndromes on the PTPN11 gene.
AB  - Multiple-lentigines (ML)/LEOPARD (multiple lentigines, electrocardiographic
      conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal
      genitalia, retardation of growth, and sensorineural deafness) syndrome is an
      autosomal dominant condition--characterized by lentigines and cafe au lait spots,
      facial anomalies, cardiac defects--that shares several clinical features with
      Noonan syndrome (NS). We screened nine patients with ML/LEOPARD syndrome
      (including a mother-daughter pair) and two children with NS who had multiple cafe
      au lait spots, for mutations in the NS gene, PTPN11, and found, in 10 of 11
      patients, one of two new missense mutations, in exon 7 or exon 12. Both mutations
      affect the PTPN11 phosphotyrosine phosphatase domain, which is involved in <30%
      of the NS PTPN11 mutations. The study demonstrates that ML/LEOPARD syndrome and
      NS are allelic disorders. The detected mutations suggest that distinct molecular
      and pathogenetic mechanisms cause the peculiar cutaneous manifestations of the
      ML/LEOPARD-syndrome subtype of NS.

PMID- 12058351
TI  - [Immunoanalytical methods of cyclosporine A determination].
AB  - The standard method for determination of CyA in blood is a good validated HPLC
      method. HPLC methods were developed which make it possible to determine not only
      the parent drug, but also the main metabolites of CyA: AMI (M17), AM9 (M1), and
      AM4N (M21). HPLC methods for determination of CyA are very laborious and
      expensive. Most transplantation centres in the world use immunoanalytical methods
      for TDM of CyA. In recent years there has been an increase in the number of users
      of nonisotopic automated methods (Abbott TDx mono, AxSYM, Dade-Behring EMIT or
      Microgenic Cedia), which render instantaneous analysis possible. The analysis of
      the results of CyA in the blood in patients after transplantation shows that all
      immunoanalytical methods overestimate the concentration of CyA against HPLC
      results. The usually presented series of results is as follows: HPLC < RIA = EMIT
      < CEDIA < AxSYM < TDx. The differences are difficult to explain only by a
      different degree of cross reactivity for particular metabolites of CyA with the
      antibody used in the immunoanalytical method. The criterion of IFCC, which should
      be met by each immunoanalytical method in order to be used for TDM of CyA, should
      be redrawn, because it is not able to ensure sufficient specificity of the
      method. A suitable, cheap, and quick analytical method for TDM of CyA is still
      wanted. Some transplantation centres, including ours, carry out not only one
      method for effective TDM of CyA.

PMID- 12058349
TI  - Genome screen to identify susceptibility genes for Parkinson disease in a sample
      without parkin mutations.
AB  - Parkinson disease (PD) is a common neurodegenerative disorder characterized by
      bradykinesia, resting tremor, muscular rigidity, and postural instability, as
      well as by a clinically significant response to treatment with levodopa.
      Mutations in the alpha-synuclein gene have been found to result in autosomal
      dominant PD, and mutations in the parkin gene produce autosomal recessive
      juvenile-onset PD. We have studied 203 sibling pairs with PD who were evaluated
      by a rigorous neurological assessment based on (a) inclusion criteria consisting
      of clinical features highly associated with autopsy-confirmed PD and (b)
      exclusion criteria highly associated with other, non-PD pathological diagnoses.
      Families with positive LOD scores for a marker in an intron of the parkin gene
      were prioritized for parkin-gene testing, and mutations in the parkin gene were
      identified in 22 families. To reduce genetic heterogeneity, these families were
      not included in subsequent genome-screen analysis. Thus, a total of 160 multiplex
      families without evidence of a parkin mutation were used in multipoint
      nonparametric linkage analysis to identify PD-susceptibility genes. Two models of
      PD affection status were considered: model I included only those individuals with
      a more stringent diagnosis of verified PD (96 sibling pairs from 90 families),
      whereas model II included all examined individuals as affected, regardless of
      their final diagnostic classification (170 sibling pairs from 160 families).
      Under model I, the highest LOD scores were observed on chromosome X (LOD score
      2.1) and on chromosome 2 (LOD score 1.9). Analyses performed with all available
      sibling pairs (model II) found even greater evidence of linkage to chromosome X
      (LOD score 2.7) and to chromosome 2 (LOD score 2.5). Evidence of linkage was also
      found to chromosomes 4, 5, and 13 (LOD scores >1.5). Our findings are consistent
      with those of other linkage studies that have reported linkage to chromosomes 5
      and X.

PMID- 12058350
TI  - [Determination of cyclosporine A using high-performance liquid chromatography].
AB  - Recent analytical possibilities of therapeutic drug monitoring (TDM) of
      cyclosporine A (CyA) both in solid organ transplanted patients and in patients
      with autoimmune diseases are described. The standard method for determination of
      CyA in blood is a validated HPLC method. HPLC methods were developed which make
      it possible to determine not only the parent drug, but also the main metabolites
      of CyA: AMI (M17), AM9 (M1), and AM4N (M21). Preparation of blood samples, their
      extractions and purifications are discussed. Chromatography is usually carried on
      C18 or CN columns by isocratic elution under high temperature (70 degrees C). CyD
      or CyC is used as the internal standard HPLC-MS method enables unambiguous
      identification of CyA metabolites after their separation on a chromatographic
      column and it is used mostly for research purposes only.

PMID- 12058352
TI  - [beta-Adrenergic receptor blockers--a group of chiral drugs: different effects of
      each enantiomer].
AB  - The present review of beta-adrenergic receptor blockers deals with different
      pharmacodynamic, pharmacokinetic and toxicological effects of individual
      enantiomers in the group of arylaminoethanols and aryloxyaminopropanols. From the
      viewpoint of beta-adrenolytic activity, (-)-enantiomers in both groups are
      several times more effective and in many beta-blockers both enantiomers show
      different therapeutic indications. The absolute configuration in the sense of
      Cahn-Ingold-Prelog system exists in (-)-enantiomers in the group of
      arylaminoethanols (R) and in the group of aryloxyaminopropanols (S). Of the beta
      blockers hitherto used in therapeutic practice, pure enantiomers are (S)-(-)
      penbutolol, (S)-(-)-timolol, and (S)-(-)-levobunolol. The hitherto research in
      this field, however, does not unambiguously answer, as the experience with
      labetalol, sotalol, and timolol shows, the question of the advantages of
      therapeutic use of pure enantiomeric forms.

PMID- 12058353
TI  - [Drug policy in Slovakia and its reflection in prescriptions. 1. Prescriptions
      for mass-produced drugs according to physician specialty].
AB  - The present paper aims at pharmacoeconomic analysis of prescriptions of
      physicians according to their specialization. The database was based on medical
      prescriptions from four pharmacies. Altogether 133,856 prescriptions were
      evaluated in two periods (the years 1999 and 2000) with different legislative
      regulations of the conditions for prescription of drugs from the funds of health
      insurance (fully covered drugs, drugs with participation of the policy holder,
      prescription and indication limitation). The results show that 1.45 kinds of
      drugs and 2.28 packages of mass-produced drugs were prescribed per 1
      prescription. The average value of drugs per one prescription was 370.28 Slovak
      crowns. General practitioners prescribed 50.5% of prescriptions, the value of
      prescribed drugs being 42.0%. As to specialization, the highest share of
      prescriptions (36.5%) was written by pediatricians, the highest value of drugs as
      expressed per 1 prescription was prescribed by diabetologists (1340.20 Slovak
      crowns). When comparing the indices under study in two periods, in the second one
      (the year 2000) the financially expressed consumption of drugs continued to show
      an increasing trend (in the case of the value of 1 prescription by 10.6%).

PMID- 12058354
TI  - [Properties of chitosan and sorption of copper ions from a copper sulfate
      solution on chitosan].
AB  - The introduction of the paper briefly describes the properties of chitosan and
      the current utilization of the aminopolysaccharides chitosan, chitin, and their
      derivatives in pharmaceutical formulations, and in the health services also as
      sorbents of heavy metals and other substances. The degree of deacetylation (64%)
      of commercially produced chitosan was estimated from measured IR spectra, and
      spectrophotometry in the visible region was employed to study the kinetics and
      equilibrium of the Cu(II) ion sorption from CuSO4 aqueous solutions. Cu(II)
      sorption on the suspended chitosan was rather slow, it took 8-12 hrs to establish
      the sorption equilibrium, but the maximum determined sorption capacity, up to 200
      mg of copper per 1 g of chitosan, greatly exceeded other adsorbents. A nearly
      stoichiometric ratio between the sorbed Cu(II) and the chitosan biopolymer
      structural units as well as decreasing sorption at lower pH (4-5) suggests
      complex formation of Cu(II) with the solid chitosan. The sorption was reversible,
      so the raw chitosan under study can be used as a high loading capacity carrier
      capable of the sorption and subsequent conditional liberation of a considerable
      amount of Cu(II) ions.

PMID- 12058355
TI  - [Antimycobacterial effects of pyrrolidinoethylester alkoxysubstituted
      phenylcarbamic acids].
AB  - Pyrrolidinoethylesters of alkoxysubstituted phenylcarbamic acids, formerly
      investigated for local anaesthetic activity, can be considered to be potential
      antituberculotics. They are effective in vitro against Mycobacterium
      tuberculosis, Mycobacterium kansasii, and Mycobacterium avium. Their effect
      increases with the length of the alkyl chain in the alkoxy group bound to the
      phenyl. The influence of the position of the alkoxyl chain on the phenyl is not
      too marked, but it seems to decrease in the series m-, p-, o-.

PMID- 12058356
TI  - [Structure and activity relationship of propafenone and alkylesters of 2-and 4
      [(3-propylamino-2-hydroxy)-propoxy]-phenylcarbamic acid].
AB  - Conformation analysis was performed in propaphenone and two potential
      antiarrhythmic agents of the carbamate type, employing the method of molecular
      mechanics for calculations. Energetically stable conformers were optimized by
      means of the quantumchemical method AM1 and the optimized structures were used to
      construct the pharmacophore. Using the programme Chem-X, four groups of stable
      conformations of these drug were found, and comparisons by means of the molecular
      graphic method were employed to graphically visualize the degree of their
      similarity and to determine the interatomic distances of the groups with free
      electron pairs and a lipophilic aromatic nucleus.

PMID- 12058357
TI  - [Study of local anesthetics. CLIX. HPLC separation of 1-methyl-2
      piperidinoethylesters of alkoxyphenylcarbamic acid].
AB  - The paper employed beta- and gamma-cyclodextrins as chiral stationary phases in
      HPLC, the mobile phases being polar organic solvents. Enantiomers of
      alkoxysubstituted esters of phenylcarbamic acids (local anaesthetics) were
      separated and various effects on the process of separation were examined.
      Primarily the effects of the composition and concentration of organic solvents
      and the effect of the presence of ionic modifiers in the mobile phase were
      investigated. The conditions of separation of the enantiomers of phenylcarbamic
      acid derivatives were found. Interactions influencing separation of enantiomers
      are also discussed.

PMID- 12058358
TI  - [Study of local anesthetics. CLX. Determination of the critical micellar
      concentration in a series of piperidinoethylesters of 3-alkoxyphenylcarbamic
      acid].
AB  - We have determined the critical micellar concentration (c.m.c) of the derivates
      type piperidinoethyl esters 3-alkoxy phenylcarbamic in the medium 0.05 mol/l and
      0.2/mol/l NaCl for using spectrophotometry methods in the UV region of the
      spectrum at temperature T = 25 degrees C and pH = 4.5-5.0. We found the parabolic
      dependence of the -lin(c.m.c.) on the (n) number of the carbon in the alkoxy
      substituent chain. Further, we have observed the facility formation of the
      micelle at the solution of 0.2 mol/l than 0.05 mol/l NaCl.

PMID- 12058359
TI  - Nonlinear ultrasound: breakdown of microscopic biological structures and
      nonthermal impact on a malignant tumor.

PMID- 12058360
TI  - Allantoin as a free-radical scavenger.

PMID- 12058361
TI  - The study of transcription and replication of the Marburg virus using a
      minireplicon system constructed on the basis of viral genome [corrected].

PMID- 12058362
TI  - Effect of the heat shock protein HSP70 on the glial scar formation in
      neurotransplantation.

PMID- 12058363
TI  - The effect of thyroidectomy on the expression of the mRNA of 5-HT2A serotonin
      receptors in the rat frontal cortex.

PMID- 12058364
TI  - Effect of factor VIII deficiency on generation of thrombin: a biomechanical
      approach.

PMID- 12058365
TI  - Production of heat shock proteins in a tumor cell in response to a combination of
      cisplatin and heat shock.

PMID- 12058366
TI  - Characterization of a panel of monoclonal antibodies and mapping the epitopes of
      hepatitis C virus proteins.

PMID- 12058367
TI  - Specificity of the high occupied molecular orbital of amino acids involved in
      formation of active centers of hemoproteins.

PMID- 12058368
TI  - Possible changes of Na(+)-ATPase kinetic characteristics in Tetraselmis viridis
      microalga upon adaptation to various concentrations of NaCl.

PMID- 12058369
TI  - Control of T-lymphocyte apoptosis and proliferation by reproduction hormones.

PMID- 12058370
TI  - Study of virus-cell interaction by the method of dielectrophoresis.

PMID- 12058371
TI  - Two rules of distribution of amino acids in the code table indicate chimeric
      nature of the genetic code.

PMID- 12058372
TI  - A perfluorocarbon droplet on the water surface: nonstationary motion induced by
      shot noise.

PMID- 12058373
TI  - Antisence oligodeoxyribonucleotides for fragments of the reverse transcriptase
      gene of the LINE-1 element of rats disturb the formation of long-term memory.

PMID- 12058375
TI  - Primitive forms of meiosis: the possible evolution of meiosis.
AB  - Meiosis is a basic process of most eukaryotes, as it forms with conjugation the
      basis of sexual reproduction. As sex seems to be present in the vast majority of
      eukaryotes, the origin of meiosis is presently unknown. Protists having optional
      or alternative sexual and asexual cycles seem to be the best targets for research
      on the evolution of meiosis. While the budding yeast Saccharomyces cerevisiae
      shows an elaborate and well-known meiotic process, the fission yeast
      Schizosaccharomyces pombe, has a much simpler meiosis, which may show some of the
      most primitive features of meiotic mechanisms. The present availability of whole
      genome sequences of many bacteria and some protists is revealing that eukaryotic
      sexual reproduction has recruited some prokaryotic processes for its own
      development. Some of these processes are analyzed and the basic role of
      chromosome linearity and telomere constitution in the development of meiosis is
      underlined.

PMID- 12058374
TI  - Species-specific differences in the organization of genes encoding kelch-like
      proteins of orthopoxviruses pathogenic for humans.

PMID- 12058376
TI  - Pigmented corpuscles in the midgut gland of Pomacea canaliculata and other
      Neotropical apple-snails (Prosobranchia, Ampullariidae): a possible symbiotic
      association.

PMID- 12058377
TI  - Lipoproteins from plasma and perivelline fluid of the apple snail Pomacea
      canaliculata.

PMID- 12058378
TI  - Estrogen receptors in mast cells from arterial walls.
AB  - We examined the presence of estrogen receptors (ER) in vascular mast cells and a
      possible genomic effect of estrogens on the expression of mast cell (MC)
      mediators such as chymase, TNF alpha, NOS and IL-10, which are known to affect
      the course of atherosclerosis. Immunocytochemical detection of mast cell tryptase
      and the co-localization of ERs in MCs from abdominal aortic vessels from 10
      fertile woman, 10 postmenopausal women and 15 men was performed. The genomic
      expression of IL-10, TNF alpha, and NOS was analyzed by RT-PCR and chymase
      activity by spectrophotometry after 24 h incubation with 17-beta estradiol (0.2
      0.5 ng/mL) in rat purified peritoneal MCs. A similar number of MCs were found in
      both intima and adventitia layers from men, and fertile and postmenopausal women,
      while ERs were detected only in the arterial walls from fertile women. The mRNA
      expressions of IL-10 and TNF alpha, as well as chymase activity, were not
      affected. A moderate increment of NO and both NOS, and a reduction in TNF alpha
      cytotoxicity was observed after incubating peritoneal MCs with 17-beta estradiol
      at a concentration of 0.5 ng/mL. Taken together, these results indicate that
      vascular MCs express ERs. The data demonstrate that estrogens can directly modify
      vascular MC activity. This is a novel mechanism of synergistic cooperation for
      the protective role of estrogens in the genesis of atherosclerosis.

PMID- 12058379
TI  - Micropropagation of Prosopis chilensis (Mol.) Stuntz from young and mature
      plants.
AB  - Prosopis chilensis (Mol.) Stuntz (Algarrobo de Chile) is an important native tree
      species that can be grown in arid and semiarid regions for wood and forage
      production and environmental protection. Developing a simple and reliable in
      vitro protocol for cloning it would enable to improve it genetically. Explants of
      P. chilensis were taken from 4 months-old plants grown in the greenhouse or from
      adult trees grown in a natural environment. Nodal segments 1-2 cm long containing
      an axillary bud were selected from elongating shoots. These cuttings were
      aseptically cultured on two agar-solid basal media, MS or BTMm, and treated with
      0.05 mg L-1 BA and 3 mg L-1 of either IAA, IBA or NAA. Sucrose (3% w/v) was used
      as carbon source. The percentage of sprouted cuttings and whole plant
      regeneration as well as its shoot and root length were recorded. Number, length
      and dry weight of shoots and roots were also measured. Rooting was successful
      with cuttings taken from young or adult plants, but explants from young plants
      showed a better response. Culturing in BTMm resulted in significantly greater
      shoot and root biomass than culturing in MS. Moreover, this response was higher
      in young explants when IBA was used as growth regulator. This paper reports a
      simple and effective method to micropropagate P. chilensis from young and adult
      plants.

PMID- 12058380
TI  - Adjuvant effects of Lactobacillus casei added to a renutrition diet in a
      malnourished mouse model.
AB  - Nutritional deficiencies are associated with impaired immune response, affecting
      the body's defence mechanisms. It is also known that Lactic Acid Bacteria (LAB)
      and fermented products such us yogurt have immunopotentiator activity and
      nutritional properties, and could thus be used as a valuable supplement in a
      renutrition diet. The aim of this study was to determine, in a non-severe
      malnutrition model, the effective dose of Lactobacillus casei (L. casei), which
      when is used as an adjuvant in a renutrition diet, would modulate the mucosal
      immune system and induce recovery of the integrity of the intestinal barrier. The
      experiments were performed on groups of malnourished and renourished BALB/c mice.
      They received after milk renutrition a supplement of different doses and periods
      of L. casei feeding. We measured body weight; hematologic values and serum
      proteins. We also characterized small intestine immunoglobulin secreting cells,
      intraepithelial leukocytes, mastocytes and goblet cells. Structural and
      ultrastructural studies were performed. Our results suggest that impaired gut
      barrier and mucosal immune function produced by malnutrition can be reversed by
      L. casei and that the dose of 10(7) cfu/day/mouse administered during 5
      consecutive days was the optimal one for recovery of the gut mucosal immune
      system. The clinical significance of these findings suggests ways for improving
      mucosal immunity, and generating protection against enteropathogens in hosts
      immunosuppressed by malnutrition.

PMID- 12058381
TI  - Prolactin-releasing activity of GHRP-5 (Momany peptide) on lactotrophs in vivo
      and in vitro.
AB  - In the present study the in vivo and in vitro effects of GHRP-5 on the PRL
      releasing activity in correlation with the morphological changes of lactotroph
      cells and their transcriptional activity were evaluated. The in vivo treatment
      (12 micrograms/100 g BW/day for 3 days) of male rats with GHRP-5 does not induce
      any significant changes in serum PRL levels. In contrast, the addition of GHRP-5
      to pituitary cell cultures increased significantly the release of PRL. This
      effect is enhanced in cell cultures of enriched lactotrophs, increasing
      significantly the secretion of PRL, the concentrations of which were 50% higher
      than that of untreated control cells. The administration of GHRP-5 provokes
      several changes in the fine structure of lactotrophs, compatible with an
      increased secretory activity. After the GHRP-5 treatment the different lactotroph
      subtypes persist but the subtype I displaying secretory granules of larger size
      (500-900 nm) and a significant development of the Golgi apparatus and RER were
      more frequently observed. These results can be correlated with a significant
      augmentation in PRL mRNA after the GHRP-5 treatment. In spite of that no
      variations in serum PRL levels were observed in vivo, following GHRP-5 treatment,
      the lactotroph population experienced evident fine structure modifications,
      concordant with an upsurge of PRL synthesis. These observations confirmed a
      direct action of GHRP-5 on receptors expressed by lactotrophs. The differential
      actions of GHRP-5 on in vivo and in vitro designs confirm a different
      effectiveness of this secretagogue to induce PRL secretion.

PMID- 12058383
TI  - Old species and new concepts in the taxonomy of Pomacea (Gastropoda:
      Ampullariidae).
AB  - The taxonomic history of the South American genus Pomacea Perry, 1810, and some
      shifts of systematic concepts during recent decades are briefly reviewed. Too
      many pre-evolutionist, shell-defined species created a gibberish, the only
      acceptable solution of which being perhaps a conventional, somewhat authoritarian
      decision based on expertise. The addition of other sources of morphological,
      biochemical, ecological or genetic information should not solve the problem if it
      is not accompanied by a sound reappraisal of the species concepts. Since the
      assumptions of each concept differ, any correspondence between them is
      irrelevant, and may drive to incompatible results. The shell variability of
      Pomacea canaliculata was acknowledged for most authors throughout more than a
      century. A recent insight into its life-history traits demonstrated they are as
      variable as the morphology. These findings stress the need of determining the
      ecological identity of any pest apple-snail population at a local scale, because
      its invading ability may be not exactly correlated to its taxonomical identity.
      Probably, all the canaliculata-like apple snails constitute a single, very
      variable "species" in most senses, even though different subsets may be
      recognized under other incommensurable concepts.

PMID- 12058384
TI  - Pomacea canaliculata (Gastropoda: Ampullariidae): life-history traits and their
      plasticity.

PMID- 12058382
TI  - Changes of inducible nitric oxide synthase in aortic cells during the development
      of hypertension: effect of angiotensin II.
AB  - Nitric oxide (NO) generation by inducible nitric oxide synthase (iNOS) in the
      vascular smooth muscle cells (VSMC), may play a role in blood vessel tone
      regulation. Lipopolysaccharide (LPS) induced iNOS activity and subsequent nitrite
      production by cultured aortic VSMC, from SHR with an established chronic blood
      pressure elevation (adult SHR) or during the period preceding the development of
      hypertension (young SHR) and from age-matched normotensive Wistar (W) rats were
      compared. Angiotensin II (Ang II) effect was also evaluated. Both basal LPS
      induced iNOS activity and nitrite accumulation were significantly lower in young
      SHR VSMC compared to young W rat cells. In contrast, adult hypertensive and
      normotensive rat cells did not differ in NO generation. Besides, young SHR cells
      exhibited a significant smaller iNOS activity and nitrites than adult SHR cells.
      After 24 h-incubation with Ang II, both variables were markedly reduced in all
      groups. The proportional reduction of iNOS activity and nitrites by Ang II was
      not different between hypertensive and normotensive rat cells, at any age.
      However, this Ang II inhibitory effect was greater in both adult SHR and W cells
      than in VSMC from young rats. In conclusion, a reduced LPS-induced iNOS activity
      and NO generation was observed in VSMC form spontaneously hypertensive rats
      before the raise of blood pressure, but not in adult hypertensive rat cells.
      Additionally, an inhibitory effect of angiotensin II on these variables is
      described. We can speculate that the impairment in vascular smooth muscle NO
      production precedes the development of hypertension in SHR and may play a
      pathophysiologic role in the early blood pressure elevation in genetically
      hypertensive rats.

PMID- 12058385
TI  - Oviductal structure and provision of egg envelops in the apple snail Pomacea
      canaliculata (Gastropoda, Prosobranchia, Ampullariidae).

PMID- 12058386
TI  - Causative agents of nosocomial mycoses.
AB  - In the last few years mycoses have been caused by fungi formerly considered to be
      harmless for humans. They cause diseases of plants and insects; some of them are
      also used in the industry. They are now usually called "emerging fungi". We
      investigated this flora with respect to their potential to cause infections in
      hospitals. These fungi are present in the air, on medical objects and
      instrumentation, in the respiratory tract and on the hands of hospital staff;
      other sources have been identified in the use of iatrogenic methods. Mycotic
      diseases, their risk factors, their clinical pictures, and spectra of agents were
      analyzed in 1990-2000; the results were compared with data in the literature.
      Transplantations were the most frequent risk factors, fungemia and abscess the
      most frequent clinical picture and filamentous fungi (genera Absidia, Acremonium,
      Alternaria, Apophysomyces, Aspergillus, Bipolaris, Cladophialophora,
      Cunninghamella, Exserohilum, Fusarium, Chaetomium, Chrysosporium, Lecythophora,
      Ochroconis, Paecilomyces, Pythium, Rhizopus, Scedosporium, Scopulariopsis) were
      the most frequent agents of nosocomial infections. These filamentous fungi and
      also some yeasts (genera Candida, Cryptococcus, Trichosporon) bring about
      different clinical syndromes in both immunocompromised and immunocompetent
      patients.

PMID- 12058387
TI  - Isolation of fluconazole-tolerant micromycetes onto different cultivation media.
AB  - On studying the dependence of quality and/or quantity of environmental
      fluconazole-tolerant micromycetes on culture medium in vitro, the highest number
      of isolates was obtained in Sabouraud agar (SA) without fluconazole (59 CFU/mg of
      soil sample at 25 degrees C and 31 CFU/mg at 37 degrees C). In the case of SA,
      fluconazole inhibited the growth of micromycetes to 83%. Significant differences
      were found between the average concentration of CFU/mg for six cultivation media
      without and with fluconazole (70 mg/L) at 25 and 37 degrees C. The genus
      Aspergillus (A. flavus, A. fumigatus, aspergilli from A. glaucus and A. niger
      group, A. nidulans, A. versicolor, A. ustus), Scopulariopsis brevicaulis and
      Penicillium sp. were the most common isolates. Sabouraud agar combined with malt
      extract agar, dichloran-18% glycerol agar and potato-dextrose agar were the most
      suitable for isolation of fluconazole-tolerant fungi.

PMID- 12058388
TI  - Effect of structure on antibiotic action of new 9-(ethylthio)acridines.
AB  - Six new 9-(ethylthio)acridine derivatives were examined for antibacterial and
      antifungal activities with 10 bacterial and 8 yeast strains. The only active
      compounds were 2- and 3-amino derivatives. The observed MICs (mg/L) for 2-amino-9
      (ethylthio)acridine (possessing the highest biological activity) were 12 (P.
      mirabilis), 30 (B. subtillis), 60 (C. freundii), 90 (E. coli), 128 (E. vulneris)
      and 500 (S. marcescens and S. aureus). Both amino derivatives have also lowest
      half-wave potential (E1/2) and field Swain-Lupton constants (describing
      oxidoreduction behavior) what supports the importance of acridine ion formation
      in the mechanism of antimicrobial action.

PMID- 12058389
TI  - Induction of phenylpropanoid metabolism by Pseudomonas fluorescens against tomato
      spotted wilt virus in tomato.
AB  - Pseudomonas fluorescens (two native strains, one collection strain and their
      strain mixtures in all possible combinations) when applied through seed, seedling
      dip, soil and on leaf significantly reduced the tomato spotted wilt virus (TSWV)
      disease. In P. fluorescens-treated plants, the peroxidase and phenylalanine
      ammonia-lyase activity increased. Accumulation of phenolic compounds and lignin
      were shown to be increased in the P. fluorescens-treated plants. Isoperoxidase
      native PAGE indicated that the peroxidase isoforms in tomato plants induced by
      fluorescent pseudomonads were different from the control plants; this suggests
      that the general phenylpropanoid pathway is probably stimulated in tomato plants
      treated which in turn led to significant reduction in TSWV.

PMID- 12058390
TI  - Alpha,beta-unsaturated 4-oxo acids in heterocylic synthesis. II. Behavior of 3
      (1,1-dioxadibenzothein-4-oyl)acrylic acid towards carbon nucleophiles under
      Michael reaction condition.
AB  - 3-(1,1-Dioxadibenzothien-4-oyl)acrylic acid (1) was condensed with compounds
      containing active methylene groups under Michael reaction conditions to furnish
      the Michael adducts (lactones 2a-c, lactams 3a-c, ketones 4a,b). The behavior of
      these adducts toward the action of hydrazine hydrate were investigated. The
      compounds were tested for their biological properties.

PMID- 12058391
TI  - Plant disease suppression and growth promotion by a fluorescent Pseudomonas
      strain.
AB  - An antibiotic- and siderophore-producing Pseudomonas strain isolated from virgin
      soils (with forest trees) displayed in vitro antibiosis against many plant
      pathogenic fungi. The presence of iron had no effect on this in vitro antibiosis.
      Seed bacterization improved germination, shoot height, root length, fresh and dry
      mass, enhanced yield and chlorophyll content of leaves in the five test crop
      plants under field conditions. Seed bacterization also reduced the number of
      infected brinjal plants grown in soil infested with Rhizoctonia solani. The
      strain produced a yellowish green siderophore in the standard succinate medium
      and both siderophore and a yellow viscous antibiotic compound in King's B medium.
      The results confirmed that the plant growth promotion was due to siderophore
      production whereas the disease suppression was due to the antibiotic substance.

PMID- 12058392
TI  - Viability and formation of conjugated dienes in plasma membrane lipids of
      Saccharomyces cerevisiae, Schizosaccharomyces pombe, Rhodotorula glutinis and
      Candida albicans exposed to hydrophilic, amphiphilic and hydrophobic pro
      oxidants.
AB  - Effects of four lipid peroxidation-inducing pro-oxidants--amphiphilic tert-butyl
      hydroperoxide (TBHP), hydrophobic 1,1'-azobis(4-cyclohexanecarbonitrile) (ACHN),
      hydrophilic FeII and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH)--on cell
      growth and on generation of peroxidation products in isolated plasma membrane
      lipids were determined in four yeast species (S. cerevisiae, S. pombe, R.
      glutinis and C. albicans) differing in their plasma membrane lipid composition.
      TBHP and ACHN inhibited cell growth most strongly, FeII and AAPH exerted
      inhibitory action for about 2 h, with subsequent cell growth resumption. S.
      cerevisiae strain SP4 was doped during growth with unsaturated linoleic (18:2)
      and linolenic (18:3) acids to change its resistance to lipid peroxidation. Its
      plasma membranes then contained some 30% of these acids as compared with some
      1.3% of 18:2 acid found in undoped S. cerevisiae, while the content of (16:1) and
      (18:1) acids was lower than in undoped S. cerevisiae. The presence of linoleic
      and linolenic acids in S. cerevisiae cells lowered cell survival and increased
      the sensitivity to pro-oxidants. Peroxidation-generated conjugated dienes (CD)
      were measured in pure TBHP- and ACHN-exposed fatty acids used as standards. The
      CD level depended on the extent of unsaturation and the pro-oxidant used. The
      TBHP-induced CD production in a mixture of oleic acid and its ester was somewhat
      lower than in free acid and ester alone. In lipids isolated from the yeast plasma
      membranes, the CD production was time-dependent and decreased after a 5-15-min
      pro-oxidant exposure. ACHN was less active than TBHP. The most oxidizable were
      lipids from S. cerevisiae plasma membranes doped with linoleic and linolenic
      acids and from C. albicans with indigenous linolenic acid.

PMID- 12058393
TI  - Rylux BSU stimulates spore germination in Trichophyton mentagrophytes and
      Aspergillus fumigatus and increases the survival rate after UV-irradiation.
AB  - Calcofluor-allied optical brightener Rylux BSU stimulated spore germination rate
      in Trichophyton mentagrophytes and Aspergillus fumigatus both if supplemented
      into Sabouraud glucose agar and if used for pretreatment of spore suspension
      prior to inoculation at low concentrations. Maximum stimulation of germination
      was obtained if 0.2% Rylux BSU was used for pretreatment in aqueous solution for
      1 d prior to inoculation (130% in T. mentagrophytes and 150% in A. fumigatus,
      respectively). Pretreatment with 1% Rylux BSU provided strong protection against
      UV-irradiation and resulted in increased yields of cultural variants after UV
      irradiation.

PMID- 12058394
TI  - Induction of morphological alterations by antineoplastic agents in yeast.
AB  - Saccharomyces cerevisiae was used as an alternative experimental model in order
      to investigate the effects of antineoplastic agents on eukaryotic cells. After
      being exposed to the most common clinically used antineoplastic agents, yeast
      cells were examined under the light microscope. Folate and pyrimidine
      antagonists, platinum derivatives, mitomycin C, actinomycin D and bleomycin
      induced alterations in yeast cellular morphology, which were not observed
      following treatment with drugs belonging to any category other than the
      antineoplastics, leading to the suggestion that these alterations could
      potentially be used as an experimental tool in pre-screening for new
      chemotherapeutic leads.

PMID- 12058396
TI  - Isozyme variation in Verticillium dahliae isolates from Crete.
AB  - Fifteen isolates of Verticillium dahliae (eight of race 1, seven of race 2; most
      from the island of Crete, Greece) were examined for isozyme and molecular
      variation. Among the isozyme banding patterns (zymograms) of six enzymes that
      were "activity-stained" after electrophoresis in 9% polyacrylamide gels,
      differences were observed in diaphorase, alpha-esterase, peroxidase and
      superoxide dismutase; 2, 2, 3 and 5 different types of zymograms were recorded,
      respectively. The zymograms could not be correlated with either race 1 or 2.
      However, all six isolates originating from the Oropedio (plateau) area of Lasithi
      (Crete) showed an esterase zymogram clearly distinguishable from the other
      isolates. No differences were observed when staining for acid phosphatase or
      aspartate aminotransferase ('glutamic-oxaloacetic transaminase'). Furthermore,
      electrophoresis of random-amplified polymorphic DNA (RAPD) in 2% agarose gels
      showed that three race-2 isolates from Oropedio of Lasithi could also be
      distinguished by the RAPD pattern generated with primer OPA-1. The variation
      observed possibly represents adaptation of V. dahliae to the Oropedio
      environment.

PMID- 12058395
TI  - Effect of berberine and (+/-)-bicuculline isolated from Corydalis chaerophylla on
      spore germination of some fungi.
AB  - Berberine and (+/-)-bicuculline were isolated from roots and leaves,
      respectively, of Corydalis chaerophylla. Both were effective in vitro against
      spore germination of some plant pathogenic fungi (Alternaria brassicicola, A.
      brassicae, A. cheiranthi, A. melongenae, A. solani, Colletotrichum musae, C.
      falcatum, Curvularia penniseti, C. lunata, C. maculans, C. pallescens, Curvularia
      sp., Erysiphe pisi, E. cichoracearum, Erysiphe sp., Fusarium udum,
      Helminthosporium spiciferum, H. penniseti, H. frumentacei, Heterosporium sp.,
      Oidium erysiphoides and Ustilago cynodontis). Berberine and (+/-)-bicuculline
      significantly inhibited spore germination of all the fungi at concentrations of
      100-1000 ppm. Berberine was effective against all the fungi at all
      concentrations; most of the fungi did not germinate at 1000 ppm. H. penniseti
      conidia did not germinate at any concentration of (+/-)-bicuculline. U.
      cynodontis was the least sensitive fungus at lower concentrations but 800 ppm
      dose was highly effective.

PMID- 12058398
TI  - Candida species isolated from cerebrospinal fluid.
AB  - In the period from November 1998 to June 2001 13 cases of nosocomial meningitis
      were reported. Candida albicans was isolated from 54% of the patients (7); C.
      parapsilosis from 23% (3); C. tropicalis from 15% (2) and C. krusei from 8% (1).
      C. albicans was isolated from the cerebrospinal fluid (CSF) of five children with
      the following diagnoses: nonspecified tumor of the central nervous system,
      Hodgkin's disease, meningitis, suspect neuroinfection, and sepsis. Examination of
      CSF allowed us to detect 2 strains of C. albicans from adult patients, one after
      neurosurgery because of a brain tumor and one with a vascular disease of the
      brain. C. parapsilosis was found in CSF from two premature children and one child
      with epilepsy. Two isolates of C. tropicalis were obtained from both blood and
      the CSF of a child from the neonatal intensive care unit and from a child from
      pediatric oncology with multiple malignant neoplasms. Only one strain of C.
      krusei was found in the oral cavity and CSF of a patient after neurosurgery
      performed after head trauma.

PMID- 12058397
TI  - Effect of plant oils and organic acids on rumen fermentation in vitro.
AB  - We determined the effect of plant oils (rapeseed, sunflower, linseed) and organic
      acids (aspartic and malic) on the fermentation of diet consisting of hay, barley
      and sugar beet molasses. Rumen fluid was collected from two sheep (Slovak Merino)
      fed with the same diet twice daily. Mixed rumen microorganisms were incubated in
      fermentation fluid, which contained rumen fluid and Mc Dougall's buffer. All
      supplemented diets significantly increased pH, molar proportion of propionate,
      and numerically decreased methane production. Lactate production was also
      decreased significantly (except with malate). Incorporation of plant oils into
      aspartate- and malate-treated incubations negated the decrease of butyrate,
      lactate and the increase of pH and ammonia with malate treatment, as well as in
      vitro dry matter digestibility and pH with aspartate treatment. The effect of
      combined additives on methane production and molar proportion of propionate was
      lower compared with additives supplemented separately. Combination of additives
      had no additive effect on rumen fermentation. All additives decreased total
      protozoan counts in rumen fluid.

PMID- 12058399
TI  - Candidal urinary tract infections caused by non-albicans Candida species.
AB  - The incidence of non-albicans Candida and non-Candida species isolated from the
      urine of patients admitted to various departments of the Faculty Hospital of the
      Medical Faculty of Safarik University in Kosice was examined. From a total of 94
      samples of analyzed urine 58 strains of C. albicans and 36 strains of yeasts
      belonging to 6 species of non-albicans Candida and non-Candida spp. were
      detected: C. parapsilosis (n = 23), C. tropicalis (6), C. krusei (3), C. robusta
      (2), C. catenulata (1) and Cryptococcus neoformans (1). In relation to the
      diagnosis, the yeasts were isolated from patients suffering from a kidneys
      disease, epididymitis, diabetes, neoplastic diseases, urogenital anomalies,
      obstructive uropathy, cystitis, prostatitis, hemolytic-uremic syndrome, and
      others.

PMID- 12058400
TI  - Detection of Shiga toxins, intimin and enterohemolysin in Escherichia coli
      strains isolated from children in eastern Slovakia.
AB  - Fifty Escherichia coli strains isolated from stool samples of 51 healthy
      children, 143 strains isolated from stool samples of 327 children with diarrhea
      and 24 strains isolated from stool samples of 21 children with suspected
      hemolytic uremic syndrome were examined for the presence of Shiga toxin-producing
      E. coli virulence factors (shiga toxin 1 and 2, intimin and enterohemolysin) and
      their genes. Vero-cell assay and latex agglutination were used for detection of
      Shiga toxin 1 and 2, TSB agar with washed erythrocytes was used for detection of
      enterohemolysin; genes encoding shiga toxin 1 and 2, intimin and enterohemolysin
      were detected using multiplex PCR. The presence of E. coli strains harboring
      genes encoding shiga toxin 1 and 2 (12 strains), intimin (34 strains) and
      enterohemolysin (12 strains) was demonstrated.

PMID- 12058401
TI  - Evaluation of strains derived from Escherichia coli W as hosts for the expression
      of penicillin G-acylase-encoding gene cloned on the recombinant plasmid pKA18.
AB  - The potential for production of penicillin G-acylase (PGA), encoded by the
      chromosomal gene pgai, of four strains belonging to a genealogical line derived
      from the strain Escherichia coli W, was evaluated in a medium with and without
      the inducer phenylacetic acid (PA). These strains were used as hosts of the
      recombinant plasmid pKA18, in which the structural gene pgac isolated from the
      strain RE3, the best host strain of a line giving the highest production, was
      cloned. The presence of the inducer reduced the copy number of the plasmid in all
      recombinant strains. Only in recombinant strain RE3 (pKA18) the reduction of the
      gene dosage of pgac resulted also in the reduction of the amount of PGA
      synthesized by the cells. The reduced activity of the cells did not result from a
      segregation of plasmid-free clones. Also the growth rate was decreased by 20 and
      40% in the host and recombinant strains, respectively. The host strain RE3
      showing the highest production of PGA was also the best host of the recombinant
      plasmid in terms of the segregational stability and copy number (198 copies per
      chromosome). The recombinant strain RE3 (pKA18) also provided the highest
      production of PGA.

PMID- 12058402
TI  - Immunostimulatory effect of Bacillus firmus on mouse lymphocytes.
AB  - Bacillus firmus (a Gram-positive nonpathogenic and harmless bacterium), was shown
      to be a strong polyclonal activator of mouse B lymphocytes as estimated by ELISA
      testing of Ig concentrations in culture supernatants after incubation of BALB/c
      mouse splenocytes with inactivated bacillus. Synthesis of all main Ig classes and
      all IgG subclasses was stimulated in vitro, the considerable effect on IgA
      formation being the most interesting feature. B cell stimulation was T cell
      dependent, as was demonstrated by the effect of B. firmus on all Ig isotypes and
      by comparison of lymphocyte response of nu/nu mice and heterozygous nu/+ mice.
      The effect of B. firmus on splenocyte proliferation was stimulatory or
      suppressive depending on the dose of the bacterium. Increased synthesis of IFN
      gamma and IL-10 (detected by ELISA in splenocyte culture supernatants) showed
      probable stimulation of Th1 and Th2 subpopulations. Considering the stimulatory
      effect on IgA formation and macrophage stimulation, B. firmus seems to be a
      prospective mucosal adjuvant and/or probiotic.

PMID- 12058403
TI  - Bacterial aerobic degradation of benzene, toluene, ethylbenzene and xylene.
AB  - Several aerobic metabolic pathways for the degradation of benzene, toluene,
      ethylbenzene and xylene (BTEX), which are provided by two enzymic systems
      (dioxygenases and monooxygenases), have been identified. The monooxygenase
      attacks methyl or ethyl substituents of the aromatic ring, which are subsequently
      transformed by several oxidations to corresponding substituted pyrocatechols or
      phenylglyoxal, respectively. Alternatively, one oxygen atom may be first
      incorporated into aromatic ring while the second atom of the oxygen molecule is
      used for oxidation of either aromatic ring or a methyl group to corresponding
      pyrocatechols or protocatechuic acid, respectively. The dioxygenase attacks
      aromatic ring with the formation of 2-hydroxy-substituted compounds.
      Intermediates of the "upper" pathway are then mineralized by either ortho- or
      meta-ring cleavage ("lower" pathway). BTEX are relatively water-soluble and
      therefore they are often mineralized by indigenous microflora. Therefore, natural
      attenuation may be considered as a suitable way for the clean-up of BTEX
      contaminants from gasoline-contaminated soil and groundwater.

PMID- 12058405
TI  - [Respiratory neurophysiology].

PMID- 12058404
TI  - Control of gene expression by FNR-like proteins in facultatively anaerobic
      bacteria.
AB  - Facultatively anaerobic bacteria are able to adapt to many different growth
      conditions. Their capability to change their metabolism optimally is often
      ensured by FNR-like proteins. The FNR protein of Escherichia coli functions as
      the main regulator during the aerobic-to-anaerobic switch. Low oxygen tensions
      activate this protein which is expressed constitutively and is inactive under
      aerobic conditions. The active form is dimeric and contains a [4Fe-4S]2+ cluster.
      The direct dissociation of the cluster to the [2Fe-2S]2+ cluster by the effect of
      oxygen leads to destabilization of the FNR dimer and to loss of its activity. The
      active FNR induces the expression of many anaerobic genes; the set comprises over
      100 of controlled genes. Many other bacteria contain one or more FNR analogues.
      All these proteins form the FNR family of regulatory proteins. Properties of
      these proteins are very distinct, sometimes even among representatives of
      different strains of the same bacterial species. FNR-like proteins together with
      other regulators (e.g., two-component system ArcBA, nitrate-sensing system NarXL,
      etc.) control a complicated network of modulons that is characteristic for every
      species or even strain and enables fine tuning of gene expression.

PMID- 12058406
TI  - [Sleep apnea-hypopnea syndrome].

PMID- 12058408
TI  - [Impaired respiratory function in patients with Parkinson's disease].

PMID- 12058409
TI  - [Respiratory dysfunction in cases of amyotrophic lateral sclerosis, muscular
      dystrophy and Guillain-Barre syndrome].

PMID- 12058410
TI  - [The features of higher brain dysfunction due to traumatic brain injury and their
      rehabilitation].

PMID- 12058411
TI  - [A lesion diagnosed by MRI in a case of transient global amnesia].
AB  - Transient global amnesia(TGA) had been recognized as a disease without abnormal
      findings on neuroimaging before magnetic resonance(MRI) imaging was practicable.
      Recently, abnormal findings on MRI reported in cases of TGA. We here reported a
      case of TGA showing a transient abnormal intensity in left hippocampus on MRI
      diffusion-weighted image. A 52-year-old man suddenly became to unable to keep his
      recent memory without histories of trauma or epilepsy. He showed no abnormal
      neurologic findings excepting for the recent memory. MRI performed within an hour
      after onset demonstrated no abnormality on T1- and T2-weighted images. Diffusion
      weighted image (b = 1,000) showed hyperintensity in the left medial temporal
      lobe, and the apparent diffusion coefficient(ADC) in this region was lower(72.8
      cm2/s) than that in the contralateral region(94.4 cm2/s). TGA was completely
      resolved 17 hours after onset.

PMID- 12058412
TI  - [Peduncular hallucinosis due to a small hemorrhage around the substantia nigra: a
      case report].
AB  - An 81-year-old female developed peduncular hallucination due to a small
      hemorrhage around the right substantia nigra is reported. Her hallucination was
      visual, not accompanying any other type of hallucination. It was vivid, colorful,
      well described, and recognized as unreal by herself. Different from most of the
      previous reports, she had no sleep abnormality and the hallucination occurred in
      daytime and at night, not relating to eye opening or closing. As the lesion of
      this case was quite restricted to around the right substantia nigra and not
      affecting the brainstem reticular formation, we speculate that the hallucination
      itself was induced by the stimulation of mesocorticolimbic system. The other
      characteristics of the hallucination such as appearing in evening, occurring with
      eye closing, and accompanying sleep disturbance might be induced when the
      brainstem involved more widely.

PMID- 12058413
TI  - [Generalized muscle weakness mimicking periodic paralysis in a patient with
      toluene abuse].
AB  - A 23-year-old Japanese man was admitted to our hospital because of acute
      generalized muscle weakness and frequent vomiting. He had been diagnosed as
      having hypokalemic periodic paralysis, since he had recurrent episodes of
      transient generalized muscle weakness with a hypokalemia. Laboratory studies have
      revealed a severe hypokalemic hyperchloremic metabolic acidosis, elevated serum
      levels of creatine phosphokinase and ammonia. The urinary level of the hippuric
      acid, a metabolic product of toluene, was found to be extremely high, suggesting
      that he had been exposed to toluene. With intravenous supplement of potasium, his
      muscle strength improved. Chronic exposure to toluene induces various
      neurological disorders, such as encephalopathy, cerebellar and pyramidal signs,
      peripheral neuropathy. In addition, it should be kept in mind that hypokalemic
      muscle weakness can be induced by the renal tubular acidosis resulting from
      chronic toluene exposure, and that it is by no means easy to distinguish
      hypokalemic periodic paralysis if it occurs recurrently.

PMID- 12058414
TI  - [A case of Fisher's syndrome after Haemophilus influenzae infection].
AB  - We report a case of Fisher's syndrome with serological evidence of antecedent
      Haemophilus influenzae infection. A 66-year-old woman developed unsteady gait and
      multiple cranial nerve palsies after upper respiratory infection. Serum anti-GQ 1
      b and anti-GT 1 a IgG antibodies were positive. In the acute phase of the
      illness, her serum had high titers of IgM, IgG and IgA anti-H. influenzae
      antibodies, which significantly decreased during the clinical course. Further
      study is needed to clarify the clinical and immunological features of Fisher's
      syndrome after H. influenzae infection.

PMID- 12058415
TI  - [Medulla and upper cervical cord compression by bilateral vertebral artery
      presented with myelopathy and drop attack: case report].
AB  - A 51-year-old man had suffered from attacks of quadri-paresis and unconsciousness
      for previous three years prior to presentation. Prior to admission, he had been
      received anticonvulsants, but his symptoms showed no improvement. Neurological
      examination revealed hyper-reflexia of his left lower extremity and moderate
      decrease of sense of pain, temperature, and tactile sensation in his left
      extremities and trunk, while vibratory sensation was normal. Magnetic
      resonance(MR) imaging revealed a flow-void area in the craniocervical junction
      and marked narrowing of the medulla oblongata and upper cervical cord by
      compression of the vertebral arteries(VA). CT myelography also showed the
      compression and narrowing of the spinal cord. Vertebral angiography demonstrated
      symmetrical running course of the arteries, which curved medially at the level of
      craniocervical junction. Suboccipital craniectomy and C1 and upper half of C2
      laminectomies were performed. After dural opening, the ventrolateral aspects of
      the lower medulla oblongata and the upper cervical cord were found to be
      compressed by the VA. The arteries were retracted dorsolaterally by GORE-TEX
      tapes so as to decompress the medulla oblongata and cervical cord, and the tapes
      were anchored to the residual part of C1 posterior arch. Postoperative MR imaging
      and CT myelography showed complete decompression, and the patient was relieved of
      his previous neurological symptoms.

PMID- 12058416
TI  - [Disseminated metastatic tumors in the brain].

PMID- 12058417
TI  - [A case of slowly progressive myoclonus, epilepsy, dementia and muscular weakness
      over 27 years].

PMID- 12058418
TI  - [Evaluation of 18F-FDG PET in acute ischemic stroke: assessment of hyper
      accumulation around the lesion].
AB  - PURPOSE: Although pathophysiology of cerebrovascular disease has been reported
      previously, few clinical studies of glucose metabolism in acute stroke have been
      published. Purpose of this study is to evaluate glucose metabolism in acute
      stroke patients by 18F-FDG PET. SUBJECTS AND METHODS: Twenty-four patients with
      acute ischemic stroke were involved in this study. All subjects underwent MRI
      (conventional T1- and T2-weighted images, diffusion-weighted imaging, and MR
      angiography), CT and 18F-FDG PET. 18F-FDG PET was performed within 1 to 7 days
      after the first episode. 18F-FDG PET images were visually evaluated as well as
      MRI and CT images. RESULTS: Four patients out of 24 showed no abnormal 18F-FDG
      accumulation, while MRI demonstrated abnormal signal area and abnormal vascular
      findings that suggested acute stroke. Decreased 18F-FDG accumulation
      corresponding with abnormal signal area on MR images was noted in 20 cases. In 7
      cases among these 20 with decreased 18F-FDG, hyper accumulation of 18F-FDG was
      recognized around the decreased accumulation area. CONCLUSION: Increased 18F-FDG
      accumulation (increased glucose metabolization) around the lesion may be due to:
      1) acceleration of anaerobic glycolysis, 2) activated repair process of damaged
      brain tissue, i.e., phagocytosis and gliosis, and 3) neuronal excitation by
      excito-toxic amino acids which can be released after ischemia.

PMID- 12058419
TI  - [Left ventricle expands maximally preceding end-diastole--radionuclide
      ventriculography study].
AB  - It has been considered that left ventricle (LV) expands maximally at the end
      diastole. However, is it exactly coincident with this point? This study was aimed
      to determine whether the maximal expansion of LV coincides with the peak of R
      wave on electrocardiogram. Thirty-three angina pectoris patients with normal LV
      motion were examined using radionuclide ventriculography. Data were obtained from
      every 30 ms backward frame from the peak of R wave. All patients showed the time
      of maximal expansion preceded the peak of R wave. The intervals from the peak of
      R wave and the onset of P wave to maximal expansion of LV was 105 +/- 29 ms and
      88 +/- 25 ms, respectively. This period corresponds to the timing of maximal
      excursion of mitral valve by atrial contraction, and the centripetal motion of LV
      without losing its volume before end-diastole may be interpreted on account of
      the movement of mitral valve toward closure. These findings suggest that LV
      expands maximally between P and R wave after atrial contraction, preceding the
      peak of R wave though conventionally as the end-diastole.

PMID- 12058420
TI  - [Rest delayed images on 99mTc-MIBI myocardial SPECT as a noninvasive screen for
      the diagnosis of vasospastic angina pectoris].
AB  - Diagnostic usefulness of 99mTc-MIBI myocardial SPECT at rest was examined in 39
      cases of coronary vasospastic angina pectoris who were diagnosed by a positive
      reaction to ergonovine provocation. SPECT was performed 45 minutes (early image)
      and 3 hours (delayed image) after the intravenous injection of approximately 600
      MBq of MIBI. Decrease in accumulation was ranked by four defect scores (0:
      normal; 1: slight decrease; 2: moderate decrease; 3: severe decrease) and the
      total defect score was evaluated semiquantitatively. The washout rate between the
      normal area and the spasm area was also evaluated quantitatively using bull's
      eye. As a result, 15 cases (15/39; 38.4%) showed decreased accumulation in the
      early image and 27 cases (27/39; 69.2%) showed decreased accumulation in the
      delayed image. All of the cases which showed decreased accumulation in the early
      image had decreased accumulation in the delayed image as well. In 6 cases (6/34;
      17.6%) showed ST wave changes during exercise ECG and 16 cases (16/34: 47%)
      showed decreased accumulation in the exercise myocardial SPECT. The washout rate
      of MIBI in the decreased accumulation area was significantly higher than that of
      the normal area. Of 32 ergonovine induced vasospastic area, 23 areas (72%)
      exhibited decreased accumulation in the delayed image for the same area.
      Decreased accumulation in the delayed image in MIBI was due to the enhanced
      washout, which, in turn, indicated declined retention of MIBI by mitochondrial
      membrane. In coronary vasospastic angina pectoris, spasm induced ischemia was
      thought to have an effect on the mitochondria. This study suggested that even
      with a normal exercise ECG and exercise myocardial SPECT, there's a strong
      possibility of coronary vasospastic angina pectoris if a decreased accumulation
      was found in the delayed image in the MIBI myocardial SPECT at rest. Hence, in
      diagnosing coronary vasospastic angina pectoris, the delayed image in the MIBI
      myocardial SPECT at rest was believed to be useful.

PMID- 12058422
TI  - [A newly developed maneuver, field change conversion (FCC), improved evaluation
      of the left ventricular volume more accurately on quantitative gated SPECT (QGS)
      analysis].
AB  - PURPOSE: To investigate whether a newly developed maneuver that reduces the
      reconstruction area by a half more accurately evaluates left ventricular (LV)
      volume on quantitative gated SPECT (QGS) analysis. METHODS: The subjects were 38
      patients who underwent left ventricular angiography (LVG) followed by G-SPECT
      within 2 weeks. Acquisition was performed with a general purpose collimator and a
      64 x 64 matrix. On QGS analysis, the field magnification was 34 cm in original
      image (Original: ORI), and furthermore it was changed from 34 cm to 17 cm to
      enlarge the re-constructed image (Field Change Conversion: FCC). End-diastolic
      volume (EDV) and end-systolic volume (ESV) of the left ventricle were also
      obtained using LVG. RESULTS: EDV was 71 +/- 19 ml, 83 +/- 20 ml and 98 +/- 23 ml
      for ORI, FCC and LVG, respectively (p < 0.001: ORI versus LVG, p < 0.001: ORI
      versus FCC, p < 0.001: FCC versus LVG). ESV was 28 +/- 12 ml, 34 +/- 13 ml and 41
      +/- 14 ml for ORI, FCC and LVG, respectively (p < 0.001: ORI versus LVG, p <
      0.001: ORI versus FCC, p < 0.001: FCC versus LVG). CONCLUSION: FCC was better
      than ORI for calculating LV volume in clinical cases. Furthermore, FCC is a
      useful method for accurately measuring the LV volume on QGS analysis.

PMID- 12058421
TI  - [Estimation by static SPECT of the radioactivity remaining after the first dose
      of two-fractionated 123I-IMP administration: the rate of increase in cerebral
      blood flow by ARG and the rate of increase in SPECT count].
AB  - We devised a method for estimating the radioactivity remaining after the first
      dose of two-fractionated tracer administration in the acetazolamide activation
      study in a facility where static SPECT is used for 123I-IMP cerebral blood flow
      scintigraphy. Three static SPECT scans were obtained over 9-min periods beginning
      10 min after the first 123I-IMP administration, to estimate the remaining
      activity until after 60 min. In 72 patients at rest, 9-min SPECT was performed 6
      times, and 11 different patterns of distribution and the fitting coefficient were
      obtained. The correlation between the actual measurement and the estimation at
      the mid scan time of 59.5 min could be expressed as y = 1.0064x - 1.9656, and r =
      0.9972 (p < 0.01). The correlation between the first and second measurements of
      cerebral blood flow in 5 patients given two-fractionated administration at rest
      could be expressed as y = 0.9919x + 0.2978, r = 0.9976 (p < 0.01), indicating the
      usefulness of this method for estimating the radioactivity remaining after the
      first dose. In 57 patients with unilateral cerebrovascular disease, the cerebral
      blood flow on the unaffected side increased by 55.4 +/- 13.1%, whereas the blood
      flow in 19 regions exhibiting severe stenosis on the affected side was increased
      only 1.4 +/- 10.5% (p < 0.01). In addition, the correlation between the rate of
      increase in cerebral blood flow and the rate of increase in SPECT count could be
      expressed as y = 0.8415x + 0.291, and r = 0.9979 (p < 0.01). Thus, with this
      method, the cerebral hemodynamic reserve test using the rate of increase in
      cerebral blood flow by the ARG method or the rate of increase in SPECT count can
      be completed within a day while maintaining the image quality of static SPECT.

PMID- 12058424
TI  - [Direct assay for urine cortisol with cortisol kit [TFB]].
AB  - We examined Cortisol Kit [TFB] for direct assay of urine cortisol. And the
      multiplication by dilution factor of urine cortisol values in this kit was
      examined. The coefficient of correlation of cortisol levels (46 urine samples)
      between Cortisol Kit [TFB] and Chemilumi ACS-Cortisol II, which is another kit
      for direct assay of urine cortisol, was r = 0.858, y = 1.86x + 38.2 (p < 0.001).
      There were differences between the both cortisol levels of each urine sample in
      spite of the good coefficient of correlation. The urine cortisol values obtained
      from the standard curve in addition of 50 microliters of zero standard were 50
      80% of the values obtained from the standard curve in the package insert. These
      results suggest that the specificity of the antibodies of both direct assay kits
      for urine cortisol may be different each other, and the multiplication by 1.09,
      the dilution factor due to the addition of zero standard to only urine sample, is
      unnecessary although it is indispensable for urine samples to add zero standard.
      Cortisol Kit [TFB] was very convenient for its easy assay procedure and short
      incubation.

PMID- 12058423
TI  - [Serial change of myocardial fatty acid metabolism in a case with severe
      myocardial ischemia].
AB  - A 66-year-old-man was admitted to our hospital because of chest pain on effort in
      October 1999. The initial images of 123I-BMIPP myocardial SPECT (BM) showed
      moderately decreased tracer uptake in the apex and the delayed images revealed
      redistribution in the apex. Coronary angiography revealed 99% stenosis in the
      proximal portion of the left anterior descending artery. Since sudden onset
      anaphylactic shock induced by contrast media developed, so percutaneous
      transluminal coronary angioplasty was not performed. The patient's symptoms were
      improved with medical treatment. On BM in March 2000, the initial images
      indicated slightly reduced uptake in the apico-anteroseptal region and the
      delayed images revealed mildly redistribution in the same area. BM in September
      2000, the initial images showed moderately reduced uptake in the apico
      anteroseptal region and the delayed images revealed high washout in the same
      area. The patient's symptoms markedly deferiorrated in March 2001, and BM initial
      images revealed slightly reduced uptake in the apico-anteroseptal region and the
      delayed images revealed redistribution in the same area again. During the
      clinical course, electrocardiography and 99mTc-tetrofosmin myocardial SPECT
      revealed no marked changes. We consider that 123I-BMIPP myocardial SPECT is
      useful in estimating myocardial ischemia.

PMID- 12058425
TI  - [Reliability of a positron emission tomography system (CTI:PT931/04-12)].
AB  - PURPOSE: The maintenance data of a PET system (PT931/04-12 CTI Inc.) was analyzed
      to evaluate its reliability. METHOD: We examined whether the initial performance
      for the system resolution and efficiency is kept. The reliability of the PET
      system was evaluated from the value of MTTF (mean time to failure) and MTBF (mean
      time between failures) for each part of the system obtained from the maintenance
      data for 13 years. RESULTS: The initial performance was kept for the resolution,
      but the efficiency decreased to 72% of the initial value. The 83% of the troubles
      of the system was for detector block (DB) and DB control module (BC). The MTTF of
      DB and BC were 2,733 and 3,314 days, and the MTBF of DB and BC per detector ring
      were 38 and 114 days. The MTBF of the system was 23 days. We found seasonal
      dependence for the number of troubles of DB and BC. This means that the trouble
      may be related the humidity. CONCLUSION: The reliability of the PET system
      strongly depends on the MTBF of DB and BC. The improvement in quality of these
      parts and optimization of the environment in operation may increase the
      reliability of the PET system. For the popularization of PET, it is effective to
      evaluate the reliability of the system and to show it to the users.

PMID- 12058426
TI  - [Usefulness of imaging method without using lead plate for sentinel lymph node
      scintigraphy].
AB  - PURPOSE: In scintigraphy of the sentinel lymph node, it is common to use a lead
      plate as a shield to reduce star artifact and scattered radiation in the portion
      surrounding the injected site of radioactive colloid. We have developed an
      imaging method without using a lead plate, and examined its usefulness in phantom
      and clinical imagings. METHODS, RESULTS: Star artifact was eliminated using a
      medium energy collimator. Effects of scattered radiation from the injection site
      were reduced by setting energy window at higher level. CONCLUSIONS: Our method
      without using a lead plate can be applied to dynamic data acquisition and imaging
      of a portion where it is difficult to place a lead plate. It also seems to be a
      useful imaging method in that it takes patients' feelings into consideration.

PMID- 12058427
TI  - [Clinical application of left ventricular volume and ejection fraction derived
      from gated SPECT data].
AB  - Left ventricular (LV) volume and ejection fraction (LVEF) derived from ECG-gated
      myocardial SPECT data are reproducible and objective. Those quantitative values,
      however, interacted according to varied factors such as a frame number per R-R
      interval, tracers, and processing-algorisms. A decrease of frame number per R-R
      interval yields underestimation of end-diastolic volume and overestimation of end
      systolic volume, resulting in underestimation of LVEF. Thus, it is important to
      change a frame number per R-R interval by the examination purpose. A good
      correlation of LVEF is usually obtained, independent of a combination of tracer
      and processing-algorism. On the other hand, LV volume does not always show
      linearity between combinations of tracer and processing-algorism. An extraction
      of myocardial edge using QGS program is deteriorating in patients with small LV
      below 20 ml. It is crucial to assess LV functional values derived from ECG-gated
      SPECT data as clinical indices, taking the varied effects into consideration.

PMID- 12058428
TI  - [Effects of amrinone in patients undergoing off-pump coronary artery bypass
      grafting].
AB  - We evaluated the effect of amrinone in 41 patients undergoing off-pump coronary
      artery bypass grafting(CABG) retrospectively. Amrinone was intravenously
      administered at the rate of 5 mcg.kg-1.min-1 after coronary artery anastomosis (A
      1 group: 11 cases) or after induction of anesthesia(A 2 group: 13 cases). The
      hemodynamic variables and use of concomitant drugs were compared among A 1, A 2
      and the non-amrinone group (control group: 17 cases). Hemodynamics was measured
      before, during, after coronary artery anastomosis, and after the chest closure.
      Catecholamine and vasodilator were used to maintain mean arterial pressure (> 60
      mmHg) and cardiac index(> 3.0 l.min-1.m-2). Mean pulmonary artery pressure, right
      atrial pressure and pulmonary artery wedge pressure were significantly higher
      during anastomosis than before anastomosis in control and A 1 group, but no
      significant changes in these parameters were observed in A 2 group. In addition,
      these variables increased significantly after chest closure in control group, but
      were unchanged in A 1 and A 2 groups. Patients with concomitant use of
      catecholamine and vasodilator in A 2 group were fewer than those in control and A
      1 group. In conclusion, in the patients undergoing off-pump CABG, infusion of
      amrinone was recommended from the end of the induction of anesthesia.

PMID- 12058429
TI  - [Intraoperative monitoring of pressure within saline-filled, endotracheal tube
      cuff in adult patients undergoing CO2 laser laryngomicrosurgery].
AB  - In laser laryngomicrosurgery, saline is injected into the endotracheal tube cuff
      to prevent airway fire. Utilizing regression analyses, we investigated the
      relation between the saline volume required to obtain optimal intracuff pressure
      and tracheal diameters in patients undergoing laser laryngomicrosurgery as well
      as in model tracheas. Although excellent linear correlations were found between
      the saline volume and the diameter of model tracheas, no significant linear or
      non-linear correlation was found between the saline volume and the patient's
      tracheal diameter. In the model tracheas, a rate of rise in the intracuff
      pressure caused by increments in the injected volume was far steeper when saline
      was injected into the cuff than when air was injected into the cuff. Addition of
      only 0.2 ml saline could result in large (> 50 mmHg) increases in the intracuff
      pressure. Also in patients, addition of 1 ml could result in notable (> 50 mmHg)
      increases in the intracuff pressure. These results suggest that the saline volume
      necessary to obtain optimal intracuff pressure is difficult to be predicted from
      the patient's tracheal diameter, and that slight increases in the saline volume
      may cause excessive increases in the intracuff pressure. The intracuff pressure
      should be tightly monitored in patients undergoing laser laryngomicrosurgery.

PMID- 12058430
TI  - [Changes of blood volume and blood propofol concentration during the anesthetic
      management of a pheochromocytoma patient].
AB  - A 44-year-old man with right pheochromocytoma was scheduled for tumor resection.
      General anesthesia was maintained with nitrous oxide (66%), oxygen (33%),
      continuous infusion of propofol (4 mg.kg-1.hr-1), and continuous epidural block
      (1.5% mepivacaine 4 ml.hr-1). During operation, cardiac output and blood volume
      (BV) were measured by pulse dye-densitometry using DDG-2001 (Nihon Kohden,
      Japan), and arterial and mixed venous blood concentrations of propofol were
      measured by high performance liquid chromatography (HPLC). After tumor resection,
      cardiac output increased without change in BV, on the other hand, both arterial
      and mixed venous blood propofol concentrations clearly decreased. In conclusion,
      during the anesthetic management with propofol in case of pheochromocytoma,
      attention should be paid to depth of anesthesia because of changing propofol
      blood concentration.

PMID- 12058431
TI  - [Diphenhydramine is useful in a parturient with hypersensitivity to local
      anesthetics to manage her delivery].
AB  - We did an obstetric management of a parturient, aged 32 years, with a history of
      local anesthetic hypersensitivity. The results of histamine release test, and
      cellular antigen stimulation test with lidocaine, mepivacaine, bupivacaine and
      preservative-free lidocaine during her pregnancy showed that all local
      anesthetics studied were positive. We used diphenhydramine as an alternative
      local anesthetic for episiotomy to the parturient during the delivery.
      Infiltration with diphenhydramine provided adequate analgesia without noticeable
      adverse reaction. One month after the delivery, we performed provocative
      challenge test with local anesthetics, and confirmed she had positive tests to
      lidocaine, mepivacaine and preservative-free lidocaine, and negative test to
      bupivacaine. Diphenhydramine is an adequate alternative of local anesthetics in
      patients with history of hypersensitivity to local anesthetics.

PMID- 12058432
TI  - [Evaluation of cardiac load by measuring brain natriuretic peptide after thoracic
      esophagectomy and gastric tube in place].
AB  - A small dose of dopamine has been routinely infused for hemodynamic stabilization
      and diuresis in patients undergoing esophagectomy and gastric tube in place until
      the seventh postoperative day in our hospital. The timing of discontinuing
      infusion of dopamine was determined by our experience. However, there was no
      rationale to determine the timing of discontinuing it. Therefore, eight patients
      with ASA physical status I or II, undergoing esophagectomy and gastric tube in
      place were studied to evaluate postoperative cardiac load using brain natriuretic
      peptide, which is a biochemical detector of left ventricular dysfunction. There
      were no hemodynamic and cardiac events including myocardial ischemia and
      infarction in any patients. The postoperative course was uneventful in all
      patients. Serum BNP increased gradually and significantly until the third
      postoperative day with increasing urine volume. Serum BNP returned to the
      baseline level on the fourth postoperative day. However, serum BNP was still high
      in 3 patients on the sixth postoperative day in spite of dopamine. We conclude
      that cardiac overload was recognized until the third postoperative day.

PMID- 12058433
TI  - [Preliminary report: dissolving effect of 8% lidocaine pump spray on the print
      mark of the Trachlight wand].
AB  - In the use of 8% lidocaine pump spray as a lubricant on the Trachlight wand, its
      print mark was found to have dissolved. We therefore studied this dissolving
      effect on the print mark with three different types of lubricant (2% lidocaine
      jelly, 8% lidocaine pump spray and glycerin). One of these lubricants was painted
      or sprayed on the wand, and after five minutes the surface was wiped with a swab.
      Both lidocaine jelly and glycerin showed no effect on the print mark, but when
      lidocaine spray was used, the mark vanished almost completely. The manufacturer
      recommends that any topical anesthetics or other active ingredients should not be
      contained in a lubricant used on the Trachlight wand. We conclude that lidocaine
      pump spray should not be used as a lubricant on the Trachlight wand.

PMID- 12058434
TI  - Zonal differences in inhibition of DNA synthesis caused by anesthetics in
      cultured rat hepatocytes.

PMID- 12058435
TI  - [Successful use of mild hypothermia therapy in a patient with severe clinical
      Reye syndrome].
AB  - This report describes a case of two-yr-old female with severe clinical Reye
      syndrome (Stage III and over), who was treated with not only conventional
      therapies but also mild hypothermia therapy. She presented acute episodes of
      tonic convulsion, hepatic dysfunction and intracranial hypertension. The first
      treatment consisted of the administration of anticonvulsant and mannitol, which
      were not effective to control intracranial pressure. Therefore, we induced mild
      hypothermia to rectal temperature of 33-34 degrees C for ten days to control
      intracranial hypertension as well as barbiturate therapy and hyperventilation
      under mechanical ventilation. Although she had hypokalemia, atelectasis of the
      right upper lung lobe and thrombocytopenia as the side effects during this
      therapy, we effectively controlled ICP. Glucose fluid therapy is recommended for
      Reye syndrome. We especially should pay attention to hypokalemia because of
      hyperventilation, absorption of potassium with insulin and transudation of
      potassium from the intestine. We determined the initiation and weaning of mild
      hypothermia therapy by findings of MRI as well as intracranial pressure. MRI
      findings will contribute to the determination of initiation and weaning of mild
      hypothermia therapy. Mild hypothermia therapy should be considered in patients
      with severe clinical Reye syndrome if conventional supportive therapies are not
      effective.

PMID- 12058436
TI  - [A case of airway obstruction after posterior occipito-cervical fusion].
AB  - A 62-year-old female with rheumatoid arthritis underwent posterior occipito
      cervical fusion. Although the operation was successfully performed, airway
      obstruction developed immediately after the extubation. We succeed in fiberoptic
      intubation. We consider that airway obstruction was caused by the preexisting
      reduction of the pharyngeal space and the occipito-cervical fusion malalignment.
      On the extubation after occipito-cervical fusion, we should always consider the
      possibility of re-intubation and its difficulty.

PMID- 12058437
TI  - [Use of magnesium sulfate during resection of pheochromocytoma].
AB  - A 75-year-old woman was scheduled to undergo resection of pheochromocytoma under
      general and epidural anesthesia. Continuous infusion of magnesium sulfate was
      initiated at the time of tracheal intubation and was terminated at the tumor
      resection. Intraoperative blood pressure and heart rate were stable, but blood
      pressure rose above 160 mmHg when the tumor was handled. Hypertension caused by
      the tumor manipulation was successfully treated with intravenous nicardipine.
      Following the tumor removal, reduced blood pressure was treated with dopamine and
      norepinephrine. After the operation, spontaneous respiration did not appear until
      120 minutes following the last vecuronium injection. Although neuromuscular
      blockade was reversed with neostigmine and atropine, muscle tone was not restored
      and satisfactory spontaneous respiration was not obtained. One hour later the
      patient was extubated. Intraoperative use of magnesium sulfate provides adequate
      hemodynamic stability for resection of pheochromocytoma, but may cause prolonged
      neuromuscular blockade. Monitoring of neuromuscular function should be essential
      and reduction of ve curonium dose should be considered on using magnesium sulfate
      intraoperatively.

PMID- 12058438
TI  - [A case of multiple organ dysfunction following postoperative epididymitis].
AB  - We report a case of multiple organ dysfunction following epididymitis. A 53-year
      old male patient was admitted to our emergency room with bilateral clavicular
      fractures, multiple costal fractures and left hemopneumothorax due to a traffic
      accident. Open reduction of the right clavicular fracture was performed under
      general anesthesia on the sixth hospital day. A bladder balloon catheter was
      inserted after induction of anesthesia. The clinical course in the perioperative
      period was satisfactory and the bladder balloon catheter was removed on the
      seventh hospital day. However, spontaneous left scrotal pain with tenderness,
      intense heat with swelling developing on the tenth hospital day, and hypotension,
      dyspnea and oliguria were noted on the eleventh hospital day. Blood chemistry
      data showed severe inflammatory findings. Chest X-ray showed acute respiratory
      distress syndrome. Blood coagulation data showed pre-disseminated intravascular
      coagulation. The patient's condition continued to deteriorate and we suspected
      septic shock due to left epididymitis. Emergent left orchiectomy was performed
      under local anesthesia on the twelfth hospital day. Postoperatively he recovered
      rapidly. We consider that multiple organ dysfunction following postoperative
      epididymitis was caused by cytokines released due to systemic inflammatory
      response syndrome (SIRS) after the trauma, operation, and placement of the
      bladder catheter. In conclusion, it is important to note that patients with SIRS
      should undergo further examinations of septic shock immediately and resection of
      the causative tissue should be performed as soon as possible.

PMID- 12058439
TI  - [Intubation in a patient with lingual tonsil hypertrophy using an intubating
      laryngeal mask airway in combination with fiberoptic intubation].
AB  - A 66-yr-old man was scheduled for colon resection under general anesthesia. There
      were no findings suggesting difficulty of airway management. After induction of
      anesthesia, manual ventilation via a facemask was suboptimal, but increased fresh
      gas flow improved it. At direct laryngoscopy after achieving muscular relaxation,
      the arytenoids and epiglottis could not be seen even by an expert
      anesthesiologist. Intubating laryngeal mask airway (ILMA) was inserted to
      patient's larynx and ventilation could be continued. Tracheal intubation through
      ILMA was impossible because of hard resistance for inserting the endotracheal
      tube. Fiberoptic bronchoscopy revealed that the hypertrophied lingual tonsil
      obstructed the aperture of ILMA. Several attempts were made for intubation using
      fiberoptic tracheal intubation technique through ILMA and finally the patient's
      trachea was intubated without any bleeding or swelling of laryngeal tissues. The
      effectiveness of ILMA for the patient with lingual tonsil hypertrophy is still
      unknown, but the insertion of ILMA might be considered for safe airway management
      in combination with a fiberscope.

PMID- 12058440
TI  - [A case of epidural hematoma associated with epidural catheterization which
      occurred on 12th days after the last medication of ticlopidine hydrochloride].
AB  - A 72-year-old woman underwent choledocholithotomy under general anesthesia
      combined with epidural block. She was complicated with hypertension, diabetes
      mellitus and angina pectoris, and was given ticlopidine hydrochloride. The
      medication was stopped 12 days before the operation. Her coagulation tests and
      platelet counts were within normal ranges. An epidural catheter was inserted at
      Th 9-10 interspace, and continuous epidural anesthesia was started for
      postoperative pain. Just after the operation, numbness and motor paralysis in
      both legs occurred. We stopped continuous epidural anesthesia, and the symptom on
      right leg improved. However, after 2 days, magnetic resonance imaging revealed
      epidural hematoma extending from Th7 to L1, and the patient underwent
      laminectomy. After a month, her motor paralysis in the left leg started to
      improve gradually. It is possible that the term of discontinuation of ticlopidine
      was not enough. We should stop antiplatelet drugs early enough, and should be
      aware of early symptoms of spinal cord compression.

PMID- 12058441
TI  - [Awake craniotomy with propofol sedation and a laryngeal mask airway: a case
      report].
AB  - A 47-year-old man with brain tumor close to the speech center was scheduled for
      biopsy under awake craniotomy. Anesthesia was maintained with continuous infusion
      of propofol and intermittent fentanyl. Airway was secured with a laryngeal mask
      throughout the surgery. During cortical stimulation, his phonation was clear and
      there was no evidence of hypoxia.

PMID- 12058442
TI  - [Postoperative seizure in an epileptic patient with dentatorubral pallidoluysian
      atrophy].
AB  - A 28-year-old male with dentatorubral pallidoluysian atrophy (DRPLA) was
      scheduled for evulsion of bone marrow nail after tibia fracture. He was diagnosed
      as having DRPLA at the age of 12. Although he was receiving anticonvulsants,
      regular seizures had occurred occasionally and his symptoms were exacerbating.
      General anesthesia was induced and maintained with intravenous propofol
      supplemented with fentanyl, nitrous oxide, and oxygen. The operation was
      performed uneventfully. After the surgery, his breathing was depressed and
      naloxone was administered to reverse the depression. Thereafter, generalized
      tonic seizure associated with involuntary movement of the left arm occurred.
      These symptoms ceased soon after rapid injection of diazepam. Inhaled and
      intravenous anesthetics have been alleged to have both proconvulsant and
      anticonvulsant activities in humans. In the present patient with DRPLA, propofol,
      fentanyl, nitrous oxide, naloxone, and neostigmine administered might be factors,
      which could have lowered the threshold for seizure activity. Further, patients
      with DRPLA might have decreased GABA in the basal ganglia, and anesthetics would
      affect GABA receptors. Thus we should be aware of occurrence of convulsion in
      DRPLA patients during and after anesthesia.

PMID- 12058443
TI  - [A successfully treated case of aspiration pneumonia with adult respiratory
      distress syndrome and shock].
AB  - Right hip replacement was scheduled for a 74-year-old man who was treated with
      morphine for cancer pain. As the patient developed dyspnea and hypoxia after
      anesthesia, he was intubated and kept under mechanical ventilation. A diagnosis
      of aspiration pneumonia with adult respiratory distress syndrome was made based
      on the detection of gall obtained from the endotracheal tube. A chest X-ray
      showed pulmonary edema. He was treated with positive pressure ventilation and
      inotropic support. As he developed severe shock 10 hours after the intubation, he
      was treated with 20 mg.kg-1 of methylprednisolone for 3 days. The steroid therapy
      was successful and he was extubated on the 6th postoperative day and was
      discharged from the ICU on the 7th postoperative day. High-dose pulse
      methylprednisolone therapy resulted in a remarkable clinical improvement.
      Corticosteroids rescue treatment is effective for such a severe case of
      aspiration pneumonia with shock when the treatment is done in the early phase of
      the pneumonia.

PMID- 12058444
TI  - [Manpower at private university hospitals in Japan].
AB  - We studied the numbers of teaching staff in anesthesiology departments and of
      patients operated on and managed by anesthesiologists at private university
      hospitals in 1999, in Japan. Questionnaires were sent to 49 institutions, and 36
      responded (response rate, 73%). The mean number of patients managed by
      anesthesiologists in an institution was 3899 (range, 942-8135). The mean number
      of patients who were managed by a staff anesthesiologist was 428 cases (range,
      118-980). The data indicate that a prompt increase in manpower at the private
      university hospitals is necessary to improve patient care, education, and
      research work.

PMID- 12058446
TI  - [A comment on five reports concerning perioperative mortality and morbidity of
      the year 1999 in Japanese Society of Anesthesiologists certified training
      hospitals].
AB  - Japanese Society of Anesthesiologists (JSA) has conducted an annual survey
      concerning anesthesia-related morbidity and mortality in JSA certified training
      hospitals. This survey was conducted through confidential questionnaires sent by
      mail to the hospitals. In 'Survey 1999', 60.3% of the hospitals responded to the
      questionnaire. The results were published in five separate reports: with special
      reference to ASA-physical status, age, anesthetic methods, operative regions, and
      'outline'. However, overall morbidity and mortality differed among the reports.
      For example, overall anesthesia-related morbidity in the report with special
      reference to ASA-PS was 0.08 (5/655,644) per 10,000 cases, although it was 0.13
      (11/793,847) in a report 'outline'. This difference was caused by imperfect
      answers from some hospitals. Some hospitals only reported the total number of
      patients in 1999 and total cases with cardiac arrest or other critical events,
      without details of distribution as to ASA-physical status, age, anesthetic
      methods, and/or operative regions. As a result, a part of critical incidents was
      reflected in the calculation of overall mortality and morbidity in the
      'outlines', but not in that of ASA-physical status, age, anesthetic methods,
      and/or operative regions. In 'Survey 2000', however this type of confusion was
      reduced, because increasing number of hospitals had answered the questionnaire
      completely.

PMID- 12058445
TI  - [Annual report of perioperative mortality and morbidity for the year 2000 at
      certified training hospitals of Japanese Society of Anesthesiologists: with a
      special reference to anesthetic methods--report of the Japanese Society of
      Anesthesiologists Committee on Operating Room Safety].
AB  - The Committee on Operating Room Safety of Japan Society of Anesthesiologists
      (JSA) sends annually confidential questionnaires of perioperative mortality and
      morbidity (cardiac arrest, severe hypotension, severe hypoxia) to Certified
      Training Hospitals of JSA. This report is a special reference to anesthetic
      methods in perioperative mortality and morbidity in 2000. Five hundreds and
      twenty hospitals reported perioperative mortality and morbidity referred to
      anesthetic methods and total numbers of reported cases were 910,007. The
      percentage of cases reported by each anesthetic method was as follows; inhalation
      anesthesia 45.47%, total intravenous anesthesia (TIVA) 6.15%, inhalation
      anesthesia + epidural or spinal or conduction block 24.48%, TIVA + epidural or
      spinal or conduction block 6.33%, spinal with continuous epidural block (CSEA)
      3.67%, epidural anesthesia 1.92%, spinal anesthesia 10%, conduction block 0.47%
      and others 1.49%. The incidence of cardiac arrest per 10,000 cases due to all
      etiology (anesthetic management, preoperative complications, intraoperative
      complications, surgery, others) is estimated to be 6.55 cases in average; 5.36
      cases in inhalation anesthesia, 30.72 cases in total intravenous anesthesia
      (TIVA), 4.62 cases in inhalation anesthesia + epidural or spinal or conduction
      block, 2.6 cases in TIVA + epidural or spinal or conduction block, 1.2 cases in
      spinal with continuous epidural block (CSEA), 0.57 cases in epidural anesthesia,
      1.65 cases in spinal anesthesia, 2.36 cases in conduction block and 46.38 cases
      in other methods. However, the incidence of cardiac arrest per 10,000 cases
      totally attributable to anesthetic management is estimated to be 0.54 cases in
      average; 0.34 cases in inhalation anesthesia, 1.07 cases in TIVA, 0.58 cases in
      inhalation anesthesia + epidural or spinal or conduction block, 0.17 cases in
      TIVA + epidural or spinal or conduction block, 0.9 cases in CSEA, 0.57 cases in
      epidural anesthesia, 0.99 cases in spinal anesthesia, zero case in conduction
      block and 1.47 cases in other methods. The incidence of severe hypotension per
      10,000 cases due to all etiology is estimated to be 11.14 cases in average; 11.31
      cases in inhalation anesthesia, 36.61 cases in TIVA, 9.29 cases in inhalation
      anesthesia + epidural or spinal or conduction block, 6.59 cases in TIVA +
      epidural or spinal or conduction block, 3.59 cases in CSEA, 6.3 cases in epidural
      anesthesia, 4.39 cases in spinal anesthesia, 2.36 cases in conduction block and
      23.56 cases in other methods. On the other hand, the incidence of severe
      hypotension per 10,000 cases totally attributable to anesthetic management is
      estimated to be 1.25 cases in average; 0.97 cases in inhalation anesthesia, 0.89
      cases in TIVA, 1.39 cases in inhalation anesthesia + epidural or spinal or
      conduction block, 1.39 cases in TIVA + epidural or spinal or conduction block,
      2.09 cases in CSEA, 3.44 cases in epidural anesthesia, 1.87 cases in spinal
      anesthesia, zero case in conduction block and zero case in other methods. The
      incidence of severe hypoxia per 10,000 cases due to all etiology is estimated to
      be 4.8 cases in average; 6.35 cases in inhalation anesthesia, 9.64 cases in TIVA,
      3.82 cases in inhalation anesthesia + epidural or spinal or conduction block,
      2.26 cases in TIVA + epidural or spinal or conduction block, 0.3 cases in CSEA,
      1.15 case in epidural anesthesia, 1.21 cases in spinal anesthesia, zero case in
      conduction block and 5.89 cases in other methods. On the other hands, the
      incidence of severe hypoxia per 10,000 cases totally attributable to anesthetic
      management is estimated to be 1.98 cases in average; 3.09 cases in inhalation
      anesthesia, 2.32 cases in TIVA, 1.3 cases in inhalation anesthesia + epidural or
      spinal or conduction block, 0.87 cases in TIVA + epidural or spinal or conduction
      block, zero case in CSEA, zero case in epidural anesthesia, 0.55 cases in spinal
      anesthesia, zero case in conduction block and zero case in other methods. The
      mortality rate of cardiac arrest within 7 postoperative days per 10,000 cases due
      to all etiology is estimated to be 3.55 (54.2%) cases in average; 3.12 (58.1%)
      cases in inhalation anesthesia, 19.29 (62.8%) cases in TIVA, 1.17 (25.2%) cases
      in inhalation anesthesia + epidural or spinal or conduction block, 0.52 (20%)
      cases in TIVA + epidural or spinal or conduction block, zero cases in CSEA, zero
      case in epidural anesthesia, 0.33 (20%) cases in spinal anesthesia, zero case in
      conduction block and 39.76 (85.7%) cases in other methods. On the other hands,
      the mortality rate of cardiac arrest per 10,000 cases totally attributable to
      anesthesia is estimated to be 0.07 (12.2%) case in average, 0.07 (21.4%) case in
      inhalation anesthesia, 0.18 (16.8%) case in TIVA, zero case in inhalation
      anesthesia + epidural or spinal or conduction block, zero case in TIVA + epidural
      or spinal or conduction block, zero case in CSEA, zero case in epidural
      anesthesia, 0.11 (11.1%) case in spinal anesthesia, zero case in conduction block
      and 0.74 (50%) case in other methods. Five major combinations of listed critical
      incidents, causes and anesthetic methods were as follows: 18.93 cases in TIVA,
      preoperative complications and severe hypotension; 18.75 cases in TIVA,
      preoperative complications and cardiac arrest; 11.07 cases in TIVA, surgery and
      severe hypotension; 6.79 cases in TIVA, surgery and cardiac arrest; 5.24 cases in
      inhalation anesthesia, preoperative complications and severe hypotension. In
      summary: 1. There was no significant difference with regard to perioperative
      mortality and morbidity due to anesthetic management among anesthetic methods. 2.
      The percentage of each anesthetic method in 2000 was not different significantly
      from that in 1999 in spite of increased cases reported. 3. Incidence of severe
      hypotension due to all etiology of TIVA in 2000 decreased significantly compared
      with that in 1999 (P < 0.05). This may be attributed to the decreased incidence
      in preoperative complication (shock) and massive bleeding due to surgery.

PMID- 12058447
TI  - Comparative toxicological assessment of a water-soluble azole administered both
      orally and by intravenous continuous infusion in cynomolgus monkeys.
AB  - The water-soluble azole, 4-[1-[(3-methylaminoacetoxymethyl-pyridin-2-yl)-methyl
      carbamoyloxy]- ethyl]-1-[(2R,3R)-3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2- (2,5
      difluoro-phenyl)-2-hydroxy-butyl]-1H-[1,2,4]triazol-4-ium chloride hydrochloride
      (hereinafter referred to as WSA), is a new water-soluble triazole anti-fungal
      compound. WSA is rapidly converted into its active metabolite after
      administration by either the intravenous or oral route. The clinical effects of
      WSA are expected to be consistent whether it is administered by injection
      (intravenous) or orally. To evaluate and compare the toxicities of WSA via oral
      and intravenous administration, repeated toxicity studies of WSA were conducted
      in cynomolgus monkeys (oral dosage levels: 0, 10, 30 and 90 mg/kg/day over a 4
      week period; intravenous infusion dosage levels: 0, 10, 30 and 60 mg/kg/day over
      a 2-week period). In addition, a 2-week oral toxicity study of the active
      metabolite of WSA was conducted with similar dosages (0, 10, 30 and 90
      mg/kg/day). From the results obtained from the evaluation, hepatotoxicity (liver)
      and endocrinological toxicity (adrenals) were the major toxicities, a finding
      which is comparable to other previously tested azole compounds. In the 4-week
      oral toxicity study, the lethal dose of WSA was determined to be 90 mg/kg.
      However, no animal mortality was observed during the 2-week intravenous
      continuous infusion study. The toxicokinetics (TK) profile of WSA at 10 and 30
      mg/kg dosages illustrated a rapid, dose-dependent conversion of WSA to its active
      metabolite, and the plasma levels of Cmax and AUC were well correlated to their
      toxicities. However, at high dosages (60 and 90 mg/kg), WSA demonstrated high
      exposure beyond the dose-proportional manner. Overall, the results obtained
      indicate that maintaining an effective concentration and a non-toxic dosage level
      would be manageable by utilizing an initial intravenous continuous infusion
      followed by oral administration.

PMID- 12058448
TI  - Development of telemetry system in the common marmoset--cardiovascular effects of
      astemizole and nicardipine.
AB  - The purpose of this study was to evaluate a telemetry system for examining the
      cardiovascular system in the conscious common marmoset. Parameters obtained were
      blood pressure, heart rate, respiratory rate, ECG, body temperature and locomotor
      activity, and these were continuously recorded on a data recorder via the
      telemetry system and then processed by a computerized system. Diurnal rhythms of
      blood pressure, heart rate, body temperature and locomotor activity were observed
      in this system. We studied the effects of astemizole (antihistamine) and
      nicardipine (Ca2+ channel blocker) on cardiovascular parameters. Astemizole at 30
      mg/kg (p.o.) and at 1 to 3 mg/kg (i.v.), prolonged QT interval and induced
      ventricular extrasystole. Torsades de pointes occurred in one of three cases at 3
      mg/kg (i.v.) and 30 mg/kg (p.o.), while it did not affect the blood pressure,
      respiratory rate and body temperature. Nicardipine at 30 mg/kg (p.o.) caused
      sustained hypotension and tachycardia. These results demonstrate the usefulness
      of the telemetry system using the common marmoset for evaluating the
      cardiovascular effects of drugs under physiological conditions.

PMID- 12058449
TI  - Molecular genetics of transmissible spongiform encephalopathies: an introduction.
AB  - Prnp knockout mice disrupted PrPC-related genes have played an essential role to
      elucidate the relationship between PrPC, a normal host gene product, and PrPSc, a
      protease-resistant, infectious PrP; Prnp knockout mice developed by Bueler et al.
      (1992) were completely protected against scrapie disease when challenged with
      mouse prions. Further, varying expression levels in PrPC were revisited along
      with a varying susceptibility of mouse prions, when mouse Prnp genes were
      introduced into Prnp% mice. How these murine models for human prion-related
      disease would contribute to the presently ongoing TSE research?

PMID- 12058450
TI  - Effects on fetal thymocyte populations and postnatal T-cell-dependent immune
      functions after maternal exposure to 5-fluorouracil during pregnancy in mice.
AB  - 5-Fluorouracil (5-FU) is a cytostatic anti-tumor drug which is known to have
      immunosuppressive activities. To assess the immunotoxic effects of 5-FU on fetal
      thymocyte populations and immune functions after birth, pregnant C57BL/6 mice
      were orally administered vehicle or 17 mg/kg/day of 5-FU during gestational days
      (GD) from 6 to 14. The fetal thymocyte populations were analyzed with flow
      cytometry (CD4/CD8 double staining), and immune functions (a mixed lymphocyte
      reaction, in vitro cytotoxic T-cell response, in vitro antibody-forming response)
      after birth were measured. Fetal thymus weight and thymocyte numbers were
      decreased by 5-FU administration. The decrease of the thymocytes was due mainly
      to the decrease of small CD4CD8 double positive (DP) thymocytes. The thymocyte
      numbers and populations recovered to the normal level 1 week after birth. The
      mixed lymphocyte response at the 6th week after birth tended to be slightly lower
      than the control levels, but the cytotoxic T-cell response and the antibody
      forming response were the same as the control levels. These results suggest that
      immune functions might recover after birth, although maternal administration of 5
      FU has a suppressive effect on fetal thymocyte maturation.

PMID- 12058452
TI  - Gonadal toxicity of an ethanol extract of Psoralea corylifolia in a rat 90-day
      repeated dose study.
AB  - Ethanol extracts of seeds of Psoralea corylifolia are proposed as food additives
      for processed food preservation. An extract was administered by admixing into
      diet at concentrations of 0, 0.375, 0.75, 1.5 or 3.0% to 10 male and 10 female
      F344 rats each for 90 days to evaluate its toxicity. Body weight gain, food
      consumption and food conversion efficiency (body weight gain per food
      consumption) were lower in the extract-treated animals, except for the 0.375%
      males, as compared to the control animals. Absolute and/or relative testes
      weights in the 1.5 and 3.0% groups and those of ovaries in the 3.0% group were
      significantly (p < 0.01) lower than in the control group. On histopathological
      examination, seminiferous tubular atrophy and Leydig cell atrophy in the testes,
      and epithelial cell atrophy in the seminal vesicles and prostate were observed in
      the 1.5 and 3.0% males. Decrease in the number of corpora lutea associated with
      frequent necrotic follicles in the ovaries in the 1.5 and 3.0% females and less
      frequent endometrial glands in the uterus in the 3.0% females were also detected.
      These results might suggest disruption of the hypothalamus-pituitary-gonadal axis
      in Psoralea corylifolia-treated rats as possible mechanisms underlying this
      gonadal toxicity.

PMID- 12058451
TI  - Assessment of quantitative dual-parameter flow cytometric analysis for the
      evaluation of testicular toxicity using cyclophosphamide- and ethinylestradiol
      treated rats.
AB  - In the drug discovery process, effects to the human spermatogenesis must be fully
      evaluated before the first human trial. To estimate testicular toxicity,
      histopathological evaluation has been recommended in addition to the traditional
      mating procedure. However, it is laborious and time-consuming. Flow cytometric
      analysis (FCM) has also been applied to estimate testicular toxicity because of
      its speed, simplicity, and the objectivity of the data. Using cyclophosphamide
      (CP)- and ethinylestradiol (EE)-treated rat testis, we attempted to validate our
      dual-parameter, DNA ploidy and cell-size FCM, in a high-throughput toxicity
      study. Our results showed that CP damaged some spermatogonia and some early
      meiotic spermatocytes and EE caused severe decrease of spermatogenic cells except
      for spermatogonia as well as marked decrease of somatic cells, most probably
      Leydig cells. This is the first report discriminating between the changes of
      spermatogonia and that of somatic cells with FCM analysis. These results
      demonstrate that this method is a very useful and powerful tool to assess
      testicular toxicity, especially in high-throughput toxicological studies.

PMID- 12058453
TI  - [Treatment for bilateral multiple lung cancers].
AB  - During a 27-year period 1,839 patients with lung cancer were treated at Kanazawa
      University Hospital. Of these 1,839 patients, 25 (1.3%) were classified as
      bilateral multiple lung cancers by Martini's criteria. They consisted of 14
      synchronous carcinomas and 11 metachronous carcinomas. For the patients with
      synchronous carcinomas, 5 underwent bilateral operation, and 5 underwent
      ipsilateral operation and contralateral combination therapy (Nd:YAG, irradiation
      or chemotherapy). Four did not undergo operation. While for the patients with
      metachronous carcinomas, 9 underwent operation for bilateral lesions, 2 were
      treated by radiotherapy for the second primary lung cancer. When a pulmonary
      resection for bilateral multiple lung cancers is required, radicality and the
      need to preserve residual respiratory function and cardiac function (FEV1.0 more
      than 500 ml/DSA, performance status) must be considered in making the decision to
      operation. The 5-year survival rate was 67%, 41%, and 33% in cases treated by
      operation for bilateral lesions, ipsilateral operation and contralateral
      combination therapy, and non-surgical therapy. Multidisciplinary treatment based
      on surgical resection contributed to good prognosis of bilateral multiple lung
      cancers. A long-term detailed follow-up is necessary to detect second lung
      carcinoma after the first operation as soon as possible.

PMID- 12058454
TI  - [Influence of preoperative factors on off-pump coronary aortic bypass grafting
      success].
AB  - Heart displacement during off-pump CABG (OPCAB) might induce the hemodynamic
      instability. We attempted to show which preoperative factors would contribute to
      an increase in that incident during OPCAB. Between February 2000, and October
      2000, 51 patients underwent CABG in Okamura Memorial Hospital. Of these patients,
      42 patients (82.4%) underwent OPCAB and 9 patients (17.6%) were operated upon
      under cardiac arrest with cardiopulmonary bypass (NOPCAB). To expose target
      coronary arteries for OPCAB, 3 deep pericardial traction stitches were placed
      near the left lower pulmonary vein (LPV), the left of the inferior vena cava
      (IVC) and the mid portion between LPV and IVC. To further assist in providing
      good presentation, patients were placed in Trendelenburg position (30 degree head
      down tilt) and the right decubitus (30 degree the right side-down tilt). There
      were no OPCAB patients to be converted to on-pump CABG during anastomosis. Mean
      number of grafts in OPCAB group was 2.5 +/- 0.1 per patient, while that in NOPCAB
      group was 3.4 +/- 0.2 (p < 0.01). The bypass patient rate were 97.1% (100/103) in
      OPCAB group and 100% (31/31) in NOPCAB group (p = NS). In both groups, bilateral
      internal thoracic arteries were actively used for reperfusion to the left
      coronary artery. In the preoperative catheterization findings, pulmonary
      capillary wedge pressure (PCW) and left ventricular end-diastolic pressure
      (LVEDP) were significantly higher in NOPCAB group than those in OPCAB group (PCW:
      14.0 vs 7.9 mmHg, LVEDP: 14.0 vs 8.7 mmHg: p < 0.05), and there was a tendency of
      low preoperative ejection fraction (EF) and cardiac index (CI) in NOPCAB group
      compared with those in OPCAB group, although there were no differences in left
      ventricular end-diastolic and end-systolic volume index (LVEDVI and LVESVI)
      between both groups. These findings suggested that PCW and LVEDP within the
      normal limit could be credited for the success with OPCAB, while an increase of
      the left ventricular volume would not contribute to the actual success.

PMID- 12058455
TI  - [Synchronous tumors consisted of bronchial carcinoid and adenocarcinoma of the
      lung].
AB  - We report a case of synchronous tumors consisted of bronchial carcinoid and
      adenocarcinoma of the lung. A 58-year-old female was referred to our hospital
      after screening, because an abnormal shadow was noted in the right lung on her
      computed tomography (CT) of the chest. CT scans showed a peripheral pulmonary
      mass in the right middle lobe and a nodule around the right lower lobe bronchus.
      The nodular lesion like swollen lymph node was diagnosed as bronchial carcinoid
      originated in B6 by bronchoscopy. The pulmonary mass was diagnosed as
      adenocarcinoma by using core needle biopsy during operation. Right middle and
      lower bilobectomy and mediastinal lymph node dissection were performed.
      Coincidence of a bronchial carcinoid and an adenocarcinoma of the same side of
      the lung is a rare occurrence.

PMID- 12058456
TI  - [Assessment of saphenous vein grafts flow by Doppler echocardiography].
AB  - In an effort to evaluate flow characteristics of the saphenous vein grafts (SVG)
      after coronary artery bypass grafting, we performed duplex scanning of SVG which
      were anastomosed to the left anterior descending artery in 12 patients, and
      compared those indexes with 34 internal thoracic artery grafts (ITAG). The SVG
      were observed with a 7.5 MHz duplex scanner through the anterior intercostal
      space. The diameter of the vessel, systolic peak velocity, and diastolic peak
      velocity were recorded in both groups, and systolic flow volume, diastolic flow
      volume, and velocity ratio were calculated. The systolic and diastolic peak
      velocity of SVG were predominantly lower than ITAG. No difference in the diameter
      and flow ratio could not be demonstrated between 2 groups. The flow volume of SVG
      were also predominantly lower than that of ITAG throughout cardiac cycle. This
      study reveals that advanced stenotic change were caused in the SVG group and
      suggest the occurrence of vein grafts disease long after coronary artery bypass
      grafting.

PMID- 12058457
TI  - [Video-assisted thoracic surgery through card-sized utility thoracotomy].
AB  - The technique of video-assisted thoracic surgery, a minimum invasive surgical
      procedure is discussed. The characteristics are as follows: through utility
      thoracotomy, which is smaller than a card of 54 x 85 mm in size, we carry out the
      procedures using both eyes-vision with right perspective and palpation with
      fingers. We use conventional tools besides endoscopic tools, such as ultra-long
      scissors of 30 cm in length, 26 cm long Pean's forceps, which have 2 groove at
      the tip that allow one to push the knot. We covered a body of a forceps, while
      tip and the other end are not covered to allow transmission of the electrostream.
      We have carried out more than 70% of standard lobectomies with modified lymph
      node dissection for lung cancer according to this technique under the same
      quality of operation as conventional open thoracotomy. The procedure did not
      differ from conventional approach in the operation time and amount of bleeding.

PMID- 12058458
TI  - [Sternal re-entry using the retractor for harvesting internal thoracic artery].
AB  - The number of redo cardiac operations, especially coronary artery bypass grafting
      (CABG), has recently been increasing mainly due to the failure of saphenous vein
      grafts. Re-opening a median sternotomy is troublesome, because of possible
      adhesion of the heart to the sternum. Preoperative computed tomography is quite
      useful and helpful in determining the degree of the adhesion of the heart and
      ascending aorta to the back of the sternum. We report here a safe and useful
      technique for sternal re-entry using a retractor for harvesting the internal
      thoracic artery (ITA). When re-opening a median sternotomy the incision is made
      to the sternal wires; the wires are then cut and removed. Small rake retractors,
      which are connected to the ITA retractor, are hooked to both ends of the left
      side of the sternum. The ITA retractor is gently wound up to lift up the sternum.
      An oscillating saw is then applied to divide the anterior table of the sternum.
      When the posterior table of the sternum is carefully divided, the left side of
      the sternum is automatically elevated slightly. Complete division of the sternum
      can be confirmed by this slight elevation. If the left side of the sternum is
      elevated a little bit more by the ITA retractor, the dissection of the adhesion
      between the sternum and the heart can be performed without assistance. This
      technique is most beneficial for a case of redo CABG with the use of the left
      ITA, but it can be applied in any patients who previously underwent median
      sternotomy.

PMID- 12058459
TI  - [Off-pump Cx grafting for unstable angina with left main trunk lesion].
AB  - Recently, off-pump coronary artery bypass grafting (OPCAB) has been rediscovered
      and spread to avoid the deleterious effect of cardiopulmonary bypass. In OPCAB,
      surgical exposure of Cx grafting site often threats the hemodynamic stability. We
      retrospectively analysed the 13 patients with acute coronary syndrome due to LMT
      lesion who underwent emergent OPCAB to accomplish the safe Cx grafting. We
      assessed the intraoperative hemodynamic changes and early results of OPCAB
      through the use of new devices and techniques. Myocardial tissue oxygen
      saturation was measured by near-infra red spectroscopy during OPCAB. All
      procedures were completed without hemodynamic deterioration and conversion to
      cardiopulmonary bypass. No hospital deaths or complications were noted. The early
      patency rate was 100 percent and perioperative maximal CK-MB was 16.6 +/- 4.7
      IU/l. Concomitant use of ischemic preconditioning and KATP opener, oxidative
      radical scavenger, PD III inhibitor, ameliorated ischemic cardiac dysfunction
      during occlusion of the coronary artery and improved the postischemic functional
      recovery. These results suggest that intra-operative compound management may
      decrease the risk of Cx grafting of OPCAB.

PMID- 12058460
TI  - [A study of isolated tricuspid valve surgery late after left heart valve
      operation].
AB  - Management of severe tricuspid regurgitation late after left heart valve
      operation is controversial. There has been reluctance to the operation due to the
      high risk of repeat operation, coexistent right ventricular dysfunction and
      pulmonary hypertension. We investigated 6 cases of isolated tricuspid valve
      surgery (tricuspid valve replacement: 2, tricuspid valve plasty: 4) late after
      left heart valve operation. Before operation, these patients showed poor general
      condition (4 cases were NYHA III or IV) but good left ventricular function [mean
      ejection fraction (EF) 66 +/- 9.6%]. Hospital mortality was 0% and the mean mid
      term actual event-free survival over 2 +/- 1.8 years was 80%. Most of patients
      demonstrated NYHA I and improvement of hepatomegaly after operation. There were
      many complications in 2 cases that had been performed previous operation more
      than 20 years before. In summary, the patient who complained symptoms due to
      right heart ventricular failure and showed good left ventricular function after
      left heart valve surgery should be considered to undergo tricuspid valve
      operation before the occurrence of other complications.

PMID- 12058461
TI  - [Coronary artery bypass grafting without cardiopulmonary bypass: MIDCAB and
      OPCAB].
AB  - Minimally invasive direct coronary artery bypass grafting via left anterior small
      thoracotomy (MIDCAB) and coronary artery bypass grafting without cardiopulmonary
      bypass (OPCAGB) are accepted technique as less invasive than conventional
      coronary artery bypass grafting (CABG). We reported our experience with these
      procedures. From 1996 to December 1999, 176 patients underwent MIDCAB or OPCAB
      with the internal thoracic artery. The left internal thoracic arteries were used
      for grafting of the left anterior descending artery (LAD) in 131 patients, LAD
      and diagonal branches sequentially in 8 patients, using free radial artery
      conduits for grafting of the right coronary artery (RAC) or left circumflex (LCx)
      in 7 patients, using radial artery conduits as Y-graft from LAD for grafting of
      the RAC or LCx in 24 patients, and bilateral internal thoracic artery grafting
      was performed in 4 patients. One patient (0.6%) died in the hospital. One patient
      (0.6%) had perioperative myocardial infarction. No patient had cerebrovascular
      accident and sever wood infection. One-hundred-seventy-four patients (98.8%) had
      resolution of their angina symptom.

PMID- 12058462
TI  - [Combined carotid endarterectomy and off-pump coronary artery bypass grafting].
AB  - Patients with angina undergoing carotid endarterectomy have a high mortality. A
      74-yaer-old man who has severe carotid stenosis was performed combined carotid
      endarterectomy and off-pump coronary artery bypass grafting successfully. At
      first, carotid endarterectomy was performed with Jamieson's specially designed
      dissector, which allow simultaneous dissection and removal blood from the
      surgical field. Secondly, then off-pump CABG was performed. Skeletonized internal
      mammary artery was harvested with ultrasound dissector. The advantage of that the
      dissected artery is not only long and greater blood flow, but also less damage to
      sternal blood flow which prevent infection and complications. Then internal
      mammary artery was anastomosed to left anterior discending artery with Octopus II
      stabilizer. After the operation, he recovered uneventfully without neurological
      complication. Combined single staged carotid endarterectomy and off-pump CABG
      appears to be a safe method.

PMID- 12058463
TI  - [Total aortic arch replacement for distal aortic arch aneurysm with adhered left
      lung: report of a case].
AB  - A 76-year-old man with a history of pleuritis and a cerebral infarct underwent a
      total arch replacement for an aneurysm of the distal aortic arch. Computed
      tomography revealed a true aneurysm having a maximum diameter of 70 mm as well as
      pleural thickening and calcification. Total arch replacement with selective
      cerebral perfusion was performed through median sternotomy and left thoracotomy.
      The myocardial ischemic time was shortened by reperfusion from the right axillary
      artery after the anastomosis of the proximal ascending aorta and the
      brachiocephalic artery. After the other branches of the arch were anastomosed, a
      distal anastomosis through the left thoracotomy was then performed using the pull
      through method, enabling minimal decortication of the adhered lung. Our surgical
      procedure for distal arch aneurysm with adhered lung involves the addition of a
      left thoracotomy, but the reduction in the myocardial ischemic time and lung
      injury are of benefit.

PMID- 12058464
TI  - [Mycotic descending thoracic aortic aneurysm complicated by pyothorax
      postoperatively: report of a case].
AB  - We experienced with a case of mycotic descending thoracic aortic aneurysm (MTAA)
      complicated by pyothorax postoperatively. The graft replacement accompanied with
      wrapping by omental pedicle flap (OPF) was performed in this case. We considered
      that causative organism for MTAA was Salmonella species, and discussed
      effectiveness of the application of OPF to MTAA.

PMID- 12058465
TI  - [Extracardiac fontan procedure in adult: report of a case].
AB  - We report a case of a 28-year-old female who underwent an extracardiac Fontan
      procedure. The subject was diagnosed as an atrioventricular septal defect
      (Rastelli classification: type C), a double outlet right ventricle, pulmonary
      artery stenosis, a hypoplasty of left ventricle, total anomalous venous return
      (Darling: Ib + IIb), and atrial flutter. She underwent a Blalock shunt and an
      aorto-pulmonary shunt at the ages of 3 and 9 years, respectively. Under a total
      CPB, an extracardiac total cavo-pulmonary connection (TCPC), using a 26 mm
      Hemashield graft, was completed. The postoperative course was uneventful. The
      complicated atrial anatomy and atrial arrhythmia indicated TCPC in this adult
      patient.

PMID- 12058466
TI  - [Aneurysm of the noncoronary sinus of valsalva associated with aortic
      regurgitation: report of a case].
AB  - A 39-year-old man has complained of palpitation and dyspnea since 8 months ago.
      With aortic regurgitation pointed out in another hospital, he was referred to our
      hospital for examination. Preoperative ultracardiography (UCG) showed a dilated
      noncoronary sinus of Valsalva and aortic regurgitation. A daughter aneurysm was
      found by aortography. There were 2 perforations and 1 pouch at the noncoronary
      sinus cusp (NCC). The noncoronary sinus of Valsalva was dilated and the orifice
      to the daughter aneurysm was noticed. The noncoronary sinus of Valsalva was
      obliterated by suturing a dacron patch on the orifice. The aortic valve was
      replaced with ATS 23 mm valve. Postoperative computed tomography (CT) showed clot
      formation outside the patch.

PMID- 12058467
TI  - [Rupture of type III acute aortic dissection into the bilateral pleural space:
      report of a case].
AB  - Rupture of type III aortic dissection into the bilateral pleural space is very
      rare. A 62-year-old man was transferred to our department because of aortic
      dissection for emergency operation. computed tomography (CT) scan revealed
      rupture of type III aortic dissection into the bilateral pleural space. He
      underwent successful prosthetic graft replacement through left thoracotomy and
      removal of a massive amount of blood from the right pleural space by chest tube
      drainage. The postoperative course was uneventful after 2 days of respiratory
      support.

PMID- 12058468
TI  - [Basaloid-squamous carcinoma of the esophagus: report of a case].
AB  - We report herein the case of a 66-year-old man with basaloid squamous cell
      carcinoma (BSCC) of the esophagus. There are only 60 cases of BSCC of the
      esophagus previously reported in Japan. In our patient, endoscopic findings
      revealed a type 2 in the lower intrathoracic esophagus (Lt), and the tumor was
      intact with the aorta (T2). A biopsy suggested that it was adenosquamous cell
      carcinoma. An operation was done on June 11, 1996. With open thoracotomy,
      esophagectomy was performed with mediastinal lymphnode dissection by posterior
      mediastinal esophagogastrostomy. Histologically, the lesion of the tumor with
      ulceration was composed of BSCC, and other lesion was composed of typical
      squamous cell carcinoma (SCC). The immunohistochemical findings of the respected
      specimens led us to suspect that the basal-layer-type SCC had transformed into
      BSCC by undergoing differentiation and expansive proliferation. According to the
      prognosis, eventually the patient died of pneumonia due to methicillin resistant
      Staphylococcus aureus (MRSA) and candida 4 years and 9 months after the surgery.

PMID- 12058469
TI  - [Castleman lymphoma originated from the posterior mediastinum resected
      thoracoscopically: report of a case].
AB  - We report thoracoscopic resection of Castleman lymphoma originated from the
      posterior mediastinum. The patient was a 19-year-old woman, who was pointed out
      to show an abnormal shadow in the left upper lung in the chest X-ray photograph.
      It was diagnosed as a blood-rich posterior mediastinal tumor by dynamic MRI, and
      thoracoscopic surgery was performed. The tumor was adjacent to the vertebral body
      of the fourth thoracic vertebra. Although operation involved 2 hours and 40
      minutes and 670 ml of bleeding due to a strong adhesion between the tumor and the
      intercostal muscle and considerable bleeding from the tumor itself, it was
      successfully removed under thoracoscopy. The tumor was elastic and hard, and 50 x
      45 x 25 mm in size. The histopathological diagnosis was a Castleman lymphoma,
      hyaline vascular type. The postoperative course was satisfactory, and the patient
      was discharged from the hospital on the 7th postoperative day. Castleman lymphoma
      originated from the posterior mediastinum tends to bleed considerably during its
      resection. If a blood-rich posterior mediastinal tumor was found preoperatively,
      thoracoscopic operation must be advanced carefully keeping this disease in mind.

PMID- 12058470
TI  - [Subdiaphragmatic bronchogenic cyst in the left crus of diaphragm: report of a
      case].
AB  - A 39-year-old man who had a subdiaphragmatic bronchogenic cyst in the left crus
      of diaphragm received surgical treatment. The cyst was located in the
      retroperitoneum just below the diaphragm and was adhered to the left crus of
      diaphragm and unconnected with any other structures. The surgically resected cyst
      was 50 x 25 x 22 mm diameter and the wall was thin and contained white turbid
      mucus. Histologically, the cyst consisted of ciliated epithelium, mucus glands,
      smooth muscle, cartilage and this evidence established the final diagnosis of
      bronchogenic cyst. The post operative course was uneventful and the patient was
      discharged 10 days after operation. This is the 4th reported case of a
      subdiaphragmatic bronchogenic cyst in the Japanese literature.

PMID- 12058471
TI  - [Histone code hypothesis].

PMID- 12058472
TI  - [Intracellular membrane fusion and SNARE hypothesis].

PMID- 12058473
TI  - [Significance of tissue engineering in regenerative medicine].

PMID- 12058474
TI  - [Cell surface expression and localization mechanisms of voltage-dependent Na+
      channels and Na+ channelopathy].

PMID- 12058475
TI  - [Conformation of a peptide ligand bound to its G-protein coupled receptor and its
      implication for ligand transportation].

PMID- 12058476
TI  - [The mechanism of neurotransmitter release: role of synaphin/complexin in
      synaptic vesicle exocytosis].

PMID- 12058477
TI  - [A molecular fossil comes to life: a long-chain polyphosphate regulates protease
      activity].

PMID- 12058478
TI  - [Construction and analysis of a human-chimpanzee comparative clone map].

PMID- 12058479
TI  - [Membrane traffic in view of protein life].

PMID- 12058480
TI  - [Intron and pre-mRNA splicing of bacteria and Archaea].

PMID- 12058481
TI  - [LIPIDBANK for Web, the newly developed lipid database].

PMID- 12058482
TI  - Neodymium: YAG capsulotomy rates after phacoemulsification with hydrophobic and
      hydrophilic acrylic intraocular lenses.
AB  - PURPOSE: To retrospectively evaluate the incidence of neodymium: YAG (ND:YAG)
      laser capsulotomies for posterior capsule opacification (PCO) seen with
      hydrophobic and hydrophilic acrylic intraocular lens implants 18 months after
      surgery. METHODS: One hundred and five eyes that had phacoemulsification with a
      continuous curvilinear capsulorhexis and implantation of either a hydrophobic or
      a hydrophilic acrylic posterior chamber IOL were evaluated in order to assess the
      incidence of PCO. Fifty-six eyes received a hydrophobic IOL (Acrysof-Alcon) and
      forty-nine eyes received a hydrophilic IOL (Galand-Visional). A standardized
      surgical protocol was performed by a single surgeon. All surgical complications
      were excluded and all patients had standardized postoperative medication and
      follow-up. RESULTS: With an average follow-up of 18 months in both groups, the
      incidence of posterior Nd:YAG laser capsulotomy for PCO was 8.9% in the
      hydrophobic group and 24.4% in the hydrophilic group, respectively (p = 0.03).
      CONCLUSION: Intraocular lenses made from hydrophobic acrylic material are
      associated with a significantly reduced rate of Nd:YAG laser capsulotomies as
      compared with intraocular lenses made from hydrophilic acrylic material.

PMID- 12058483
TI  - Leading causes of blindness worldwide.
AB  - The main causes of blindness and visual disabilities, as described in documents
      published by the World Health Organization (WHO), are discussed.

PMID- 12058484
TI  - Corneal hydrops associated with vernal conjunctivitis as a presenting sign of
      keratoconus in a Congolese child.
AB  - PURPOSE: To report a case of unilateral corneal hydrops associated with vernal
      conjunctivitis as a presenting sign of keratoconus. METHOD: Case report. A 10
      year-old girl with corneal hydrops of the left eye. RESULT: Visual acuity in the
      affected eye was hand motions and slit-lamp examination revealed a left
      keratoconic, ectasis, edematous cornea with mild vernal conjunctivitis.
      CONCLUSION: Hereditary and environmental factors may contribute to the etiology
      of keratoconus and corneal hydrops.

PMID- 12058485
TI  - Presenting signs of retinoblastoma in Congolese patients.
AB  - OBJECTIVE: To report the relative frequency of the signs of presentation in
      Congolese children with retinoblastoma. METHODS: A retrospective study was
      undertaken of all (29) patients with retinoblastoma examined between January 1995
      and December 2000. RESULTS: There were 19 (66%) boys and 10 (34%) girls. For all
      cases, mean age at diagnosis was 2.94 years +/- 1.6 (range, four months to six
      years). For bilateral cases, it was 1.12 year +/- 1.4 (range, two months to three
      years) whereas for unilateral cases it was 3.23 years +/- 1.5 (range, four months
      to six years) (P = 0.016). More than seven distinct signs were identified.
      Leukocoria was the most common presenting sign in 49% of diagnosed cases followed
      by proptosis (28%). Other signs were strabismus, red eye, anterior scleral
      staphyloma, hyphema and buphthalmia. CONCLUSION: Strabismus seemed to be uncommon
      whereas proptosis is important in our small series when compared to signs
      reported in the developed world.

PMID- 12058486
TI  - Subconjunctival Loa Loa worm: case report.
AB  - A 38-year old Ghanaian suddenly had the sensation of a foreign body in his right
      eye. Slit-lamp examination revealed a transparent worm underneath the
      conjunctiva. With topical anesthesia, the complete worm, 3.5 cm long, was removed
      surgically. A microbiological analysis at the Institute of Tropical Medicine
      confirmed the diagnosis of Loa Loa. Laboratory tests showed negative blood
      eosinophilia, positive blood film examination for microfilariae and positive
      results for filarial serology. The postoperative treatment consisted of
      progressive doses of di-ethyl-carbamazine (50-->100-->200 mg/d). A
      subconjunctival Loa Loa worm is rare in Belgium and usually occurs in immigrants
      or travellers returning from Tropical (Equatorial) West and Central Africa. Our
      patient visited Nigeria in 1985 and Ivory Coast in 1986. Those regions are highly
      endemic for Loa Loa.

PMID- 12058487
TI  - The Jules Francois Memorial lecture. The collaborative ocular melanoma study and
      management of choroidal melanoma.

PMID- 12058488
TI  - Three-dimensional posterior segment ultrasonography: clinical experience.
AB  - PURPOSE: To introduce a commercially available three-dimensional ultrasonography
      unit into everyday clinical practice and to evaluate the qualitative and
      quantitative information of the acquired images and to clarify the indications
      for 3-D echography. MATERIALS AND METHODS: 3-D scanning was performed on 59
      referred patients with indications for conventional B/A-scan. On 7 patients with
      an intraocular mass with well-delineated borders 10 repeated volume measurements
      were carried out. RESULTS: The duration of the ultrasound examination was
      extended with 8-10 min. 3-D echography offered images of unique perspectives, not
      previously available with conventional B-scan. The digital technology allowed
      easy (re)evaluation and follow-up. The coefficient of variation of the repeated
      volume measurements was less than 5% for all the patients. The standard
      deviations ranged from 2.22 to 4.75 mm3. CONCLUSIONS: At its current level of
      technological development 3-D posterior segment ultrasonogaphy left the status of
      an entirely research laboratory tool and entered the clinical practice.
      Nevertheless 3-D imaging is neither a rival nor a substitute of conventional B
      scan since it is static and needs time intervals for reconstruction. However 3-D
      ultrasonography is a useful clinical supplement to conventional B/A echography in
      departments to which a substantial number of complicated cases (esp. intraocular
      tumours) is referred. It enables volume measurements with good intraobserver
      reproducibility and is excellent for teaching and training purposes of
      ophthalmology residents.

PMID- 12058489
TI  - [Can vitrectomy without use of microscissors improve results of surgery for
      proliferative diabetic retinopathy?].
AB  - In order to test the hypothesis that in proliferative diabetic retinopathy
      surgery the vitrectomy without the use of microscissors could improve the results
      and decrease the rate of complications as well as the operating time, two groups
      are compared in a consecutive series of 24 eyes, operated on with or without
      scissors, and with a minimum follow-up of 6 months. The study shows that the
      vitrectomy without scissors offers a higher percentage of eyes with a
      postoperative visual acuity at least two lines better than the preoperative
      visual acuity. It shows also a trend for a shorter surgery, with fewer
      complications in case of vitrectomy without scissors.

PMID- 12058490
TI  - Successful photodynamic therapy combined with laser photocoagulation in three
      eyes with classic subfoveal choroidal neovascularisation affecting two patients
      with multifocal choroiditis: case reports.
AB  - Multifocal choroiditis (MC) is an idiopathic choroidal inflammatory disease
      affecting young subjects. Secondary choroidal--and often central-
      neovascularisation is a frequent complication leading to a poor visual prognosis.
      Photodynamic therapy (PDT) has now proven to be successful to treat classic
      subfoveal choroidal neovascularisation in age-related macular degeneration and in
      pathologic myopia. We describe the treatment applied to classic choroidal
      neovascularisation in two young women with MC, two eyes with subfoveal
      neovascular membrane and one eye in which new vessels encroach the foveal
      avascular zone. PDT has been useful in the three reported eyes, with stable or
      improved visual acuity. In two of them, it even made the membrane retract and
      become extrafoveal, allowing a secondary treatment using conventional laser.

PMID- 12058491
TI  - A chance to grow.
AB  - Health-care teams taking part in the Clinical Governance Development Programme
      are helped to bring about necessary changes in the way their organisations work,
      while developing themselves personally and professionally.

PMID- 12058492
TI  - Skills needed by the nurses of the future.
AB  - Nurses practising in the 21st century may work in hospitals, the community or one
      of the new walk-in centres, but all must remember those core skills of nursing
      care that patients value, as well as keeping up to date with modern technologies
      and practices.

PMID- 12058494
TI  - Walk-in centres: are they the future?

PMID- 12058493
TI  - Core skills and competencies.

PMID- 12058495
TI  - Developing nurse leaders of the future.
AB  - Nurse leaders need to combine clinical excellence with the ability to harmonise
      staff's personal goals, the professional agenda and the goals of the
      organisation.

PMID- 12058496
TI  - Lifelong learning, CPD and you.
AB  - The essence of clinical governance is continuing professional development (CPD)
      for all professional staff. A system is now in place to disseminate and support
      CPD throughout the NHS, from national to local level.

PMID- 12058497
TI  - Easing the path back to nursing practice.
AB  - With staff shortages reaching crisis level, the government is keen to encourage
      back nurses who have taken a career break. For one nurse, this has worked well.

PMID- 12058499
TI  - [What is the future of the genetic revolution in ophthalmology?].

PMID- 12058498
TI  - A voice for nurses in primary care.
AB  - Primary care groups offer a new opportunity for practitioners in the community to
      broaden their experience--and share it with members of other professions.

PMID- 12058500
TI  - [Progress in somatic gene therapy of retinal degeneration in the animal model].
AB  - More than 60 genes responsible for human retinal dystrophies have already been
      identified. Most of them are either expressed in the photoreceptor or in the
      retinal pigment epithelium (RPE). Therefore these cells have become the target of
      new therapeutical strategies on a molecular level. The most promising approach at
      present is somatic gene therapy, which has been developed over the last years and
      the principle has now been established in animal models. For gene therapy of
      inherited retinal degeneration, as for gene therapy in general, gene transfer has
      to be proven to be not only efficient but also safe. This has recently been
      achieved using the adeno-associated virus (AAV) as a vector to express a
      therapeutic gene within the photoreceptor cell. It could be demonstrated in mouse
      and dog models of retinal degeneration that expression of the therapeutic
      transgene leads to anatomical and functional restitution of degenerating
      photoreceptors. A significant immune response to AAV has not been detected so
      far. In this paper the recent success of gene therapy of retinal degeneration in
      animal models is reviewed.

PMID- 12058502
TI  - [Objective determination of optical density of xanthophyll after supplementation
      of lutein].
AB  - BACKGROUND: It is thought that a high optical density of xanthophyll has a
      protective effect against the development of aggregated macular degeneration. The
      aim of this study was to investigate whether an increase of the optical density
      of xanthophyll in the macula after a supplementation of lutein can be proven by
      objective methods. Most methods applied for the determination of the macular
      pigment require the co-operation of the proband and the ability for foveal
      fixation. METHOD: Imaging spectrometry and the evaluation of laser scanner images
      taken at 488 nm will be presented. In contrast to psychophysical methods, both
      methods are independent of the patients ability for foveal fixation. RESULTS:
      Even by evaluation of laser scanner images taken as in fluorescence angiography
      but without inserting the blocking filter, the 2-dimensional distribution of
      xanthophyll can be determined. In 10 probands taking 6 mg lutein daily over 40
      days, an increase of the optical density could be determined at least in some
      probands. The optical density reached a plateau 30 days after starting the
      supplementation of lutein. CONCLUSION: The assumed protective effect of
      xanthophyll against age-related macular degeneration can be influenced by
      supplementation of lutein under objective control.

PMID- 12058503
TI  - [Modified Heidelberg Retinal Tomograph HRT. Initial results of in vivo
      presentation of corneal structures].
AB  - BACKGROUND: At present, confocal tandem scanning microscopes with halogen or
      mercury lamps are used to depict all corneal structures in vivo, e.g., before and
      after PRK or LASIK. Insufficient imaging quality and irregular corneal
      illumination are the main problems for automatic quantitative evaluation of the
      keratocyte density when applying this instrument. A high correction is required
      for correcting the background irregularities of pictures. Our aim was to find out
      whether it is possible to change the Heidelberg retina tomograph (HRT) into a
      high-resolution digital laser scanning microscope for the visualization of
      anterior segments of the eye, coupled with a special evaluation software.
      MATERIAL AND METHOD: We developed a lens adapter for the HRT that focusses the
      laser beam onto the cornea by combining with an external, computer-controlled
      hydraulic z-scan sledge. By using a programmable adaptation for the external
      stepmotor on the z-scan sledge in combination with all internal control functions
      and patient data, it is possible to create a digital confocal laser scanning
      microscope with retention of all the original HRT functions. For evaluation of
      the corneal images and automatic count of keratocytes, we used special 3D and
      Chemotaxis software. RESULTS: First investigations show a regular illumination of
      all corneal structures as the epithelium, endothelium, and keratocytes. The
      hydraulic z-scan allowed a precise shift of the focus through the cornea to take
      series of images for the evaluation of the keratocyte profile and 3D
      reconstruction of all corneal structures.

PMID- 12058501
TI  - [Alcohol-induced morphologic and biochemical corneal changes].
AB  - In our cornea bank, it was noticed that corneas from donors with alcoholism
      seemed to be of lower quality than corneas from other donors. High blood ethanol
      concentrations can induce high alcohol concentrations in aqueous and vitreous
      humor. This could be demonstrated in the case of a lethal alcohol intoxication.
      We conducted in vitro experiments to clarify the question of alcohol-induced
      changes of corneas. The corneas were stored in a standardized culture medium
      including ethanol, formic acid, methanol, and acetaldehyde in concentrations to
      be expected in chronic alcoholism. During cultivation over 4 weeks, endothelial
      morphology and extent of aspartic acid racemization in stromal proteins were
      evaluated. The extent of aspartic acid racemization served as a biochemical
      parameter of alcohol-induced protein changes of the corneas. In the in vitro
      experiments, a drop in the endothelial cell counts could be seen in corneas
      stored in culture medium with acetaldehyde. The extent of aspartic acid
      racemization increases in corneas stored in medium containing ethanol, which
      obviously is the result of alcohol-induced protein degradation. High
      concentrations of ethanol and its metabolics can be detected in vitreous and
      aqueous humor in chronic alcoholism. Clearly, these concentrations have a direct
      toxic effect on the corneal endothelium (acetaldehyde) and on the stromal
      proteins (ethanol).

PMID- 12058504
TI  - [Ocular involvement in nail-patella syndrome (#161200)].
AB  - PURPOSE: The "nail-patella syndrome" (NPS) is an autosomal dominant hereditary
      systemic disease. The underlying defect of the LMX1B gene is localised on
      chromosome 9q34 and causes various typical clinical signs such as
      onychodysplasia, patella hypoplasia, renal involvement and open angle glaucoma.
      PATIENTS: A 42-year-old mother and her 4-year-old son were examined in our
      hospital in order to exclude ocular involvement in a genetically confirmed "nail
      patella syndrome". A clinical examination including corneal topography,
      gonioscopy as well as measurement of intraocular pressure and bulbus length was
      performed. RESULTS: The examination of both patients showed NPS-specific
      symptoms, however the boy revealed no indications of glaucoma. He suffered from
      marked amblyopia caused by excessive astigmatism of the left eye and a bilateral
      moderate hyperopia. CONCLUSION: Because of the co-segregation between the
      syndrome and open angle glaucoma, NPS patients should undergo regular
      ophthalmological controls including measurement of intraocular pressure.
      Experiments on mice have shown that mutations of the LMX1B gene result in
      alterations of several structures of the anterior segments. Thus, the described
      refraction abnormality could be the consequence of structural changes at the
      corneal level due to NPS.

PMID- 12058505
TI  - [Phacoemulsification of human lens nucleus with a water jet].
AB  - BACKGROUND: Today, phacoemulsification with ultrasound represents the gold
      standard in cataract surgery. Nevertheless, new technologies for this operation
      are being developed to reduce the loss of endothelial cells, the heating of the
      tissue, and the size of the accesses. In addition to bimanual
      phacoemulsification, laser phacoemulsification, and mechanic phacolysis, the
      waterjet is discussed as an alternative. MATERIALS AND METHODS: Human soft and
      hard nuclei of the lens obtained by extracapsular cataract extraction (ECCE) were
      divided in the water bath with the waterjet, whereby the parameter pressure was
      varied and the time needed for fragmentation was recorded. RESULTS: In spite of
      different consistencies, all nuclei could be divided under the direct force of
      the waterjet. For the emulsification of hard nuclei of the lens, a pressure of no
      less than 10 bar was necessary. This value was obviously higher than a lens
      capsule can tolerate. For the fragmentation of soft nuclei of the lens with lower
      acceptable pressures of 5 bar, comparatively long operating times (in some cases
      over 5 min) were measured. This means that also in these cases a pressure of 10
      bar was required. CONCLUSION: Intraocular use of the waterjet with direct effect
      of the stream with these pressures is not justifiable. Instruments for waterjet
      phacoemulsification should be developed which pose no danger to the corneal
      endothelium and lens capsule.

PMID- 12058506
TI  - [Macrophage depletion inhibits leukocyte recruitment in experimental melanin
      induced uveitis (EMIU)].
AB  - BACKGROUND: To study the role of macrophages in experimental melanin-induced
      uveitis (EMIU), we used the method of intravital microscopy to analyse changes in
      leukocyte adhesion to iris venules of live rats with EMIU after pretreatment with
      liposomal clodronate. MATERIALS AND METHODS: EMIU was induced in Lewis rats (n =
      48) by intraperitoneal immunisation with bovine crude melanosomes emulsified in
      complete Freund's adjuvant (CFA) and pertussis toxin (PTX). Control animals
      received CFA and PTX only (n = 12) or no injection (n = 6). Animals were treated
      with liposomal clodronate (DMDP-lip) or empty liposomes on days -2, +1, 4, 6 and
      8. Using IVM, postcapillary iris venules of rats were examined to quantify
      leukocyte rolling and firm adhesion to the vascular endothelium. RESULTS:
      Depletion of macrophages caused a decreased percentage of rolling leukocytes on
      day 8 (2 +/- 1.1% vs 15.2 +/- 1.6%, DMDP-lip vs EMIU, mean +/- SEM, ANOVA, p <
      0.05) and day 10 (2.6 +/- 0.3% vs 14.2 +/- 1.6%). A significant decline in the
      number of firmly adherent leukocytes was detected on days 8 and 10 (88 +/- 13/mm2
      vs 175 +/- 18/mm2 and 129 +/- 13/mm2 vs 372 +/- 31/mm2, DMDP-lip vs EMIU).
      Treatment with empty liposomes showed no changes in leukocyte firm adhesion.
      CONCLUSIONS: Elimination of macrophages prevents the induction of EMIU. In
      autoimmune-mediated uveitis, macrophages play a crucial role in the initiation of
      leukocyte-endothelium interaction.

PMID- 12058507
TI  - [Traction retinal detachment, optic atrophy, apallic syndrome after shaking
      trauma in an infant].
AB  - INTRODUCTION: Ophthalmological examinations are important in children with
      suspected shaken baby and/or battered child syndrome. Retinal and epiretinal
      haemorrhages can indicate non-accidental injuries. We observed a case of
      extensive retinal hemorrhages, edema of the optic disc followed by development of
      optic atrophy, neovascularisation and tractional retinal detachment over the
      course of months. CASE REPORT: A 6-week-old infant with no history of systemic
      disease or trauma was admitted to the children's hospital because of a disorder
      of consciousness, respiratory insufficiency, taut fontanel and dilated pupils
      with sluggish reaction to light. A subdural haematoma was diagnosed.
      Ophthalmological examination showed no signs of trauma in the anterior segment.
      Ophthalmoscopy revealed extensive retinal haemorrhages and swollen optic nerve
      heads. During the next months optic atrophy, subretinal fibrosis at the posterior
      pole, neovascularisation at the optic disc and non-rhegmatogenous retinal
      detachment developed. The child is in a persistent vegetative state. DISCUSSION:
      Non-accidental injuries can cause direct trauma and indirect traumatic sequelae.
      Retinal haemorrhages, especially in conjunction with unexplained trauma or
      changes of consciousness should arouse suspicion of shaken baby syndrome. The
      ophthalmologist should emphasize this and strongly recommend further
      investigation if not previously undertaken.

PMID- 12058508
TI  - [Critical comments on the ARED study].

PMID- 12058510
TI  - [Bilateral subconjunctival foreign bodies. Loiasis with bilateral Loa
      ophthalmia].

PMID- 12058509
TI  - [Vitamins and trace elements in age-related macular degeneration. Current
      recommendations, based on the results of the AREDS study].

PMID- 12058511
TI  - [Cloudiness of a PMMA intraocular lens. "Snowflake" degeneration].

PMID- 12058512
TI  - [Scleral buckling operations in rhegmatous retinal detachment].

PMID- 12058513
TI  - Therapists awake! The challenge of evidence-based occupational therapy.

PMID- 12058514
TI  - A synthesis of the effects of occupational therapy for persons with stroke, Part
      I: Restoration of roles, tasks, and activities.
AB  - This article synthesizes research findings regarding the effects of occupational
      therapy on the restoration of role, task, and activity performance for persons
      who have had a stroke, with the purpose of guiding practice and research. It is
      the first of a two-part review of studies. Part II synthesizes research findings
      regarding the effects of occupational therapy on remediating impairments. Part I
      includes 15 studies involving 895 participants (mean age = 70.3 years). Of these
      studies, 11 (7 randomized controlled trials) found that role participation and
      instrumental and basic activities of daily living performance improved
      significantly more with training than with the control conditions. We conclude
      that occupational therapy effectively improves participation and activity after
      stroke and recommend that therapists use structured instruction in specific,
      client-identified activities, appropriate adaptations to enable performance,
      practice within a familiar context, and feedback to improve client performance.
      Empirical research to verify these findings and to characterize the key
      therapeutic mechanisms associated with desired outcomes is needed.

PMID- 12058515
TI  - A synthesis of the effects of occupational therapy for persons with stroke, Part
      II: Remediation of impairments.
AB  - This article is the second of a two-part synthesis of research regarding the
      effects of occupational therapy to improve activity and participation and to
      reduce impairment for persons with stroke. Part I synthesized research findings
      for restoration of role participation and activity performance. Part II
      synthesizes research findings regarding the effects of occupational therapy to
      remediate psychosocial, cognitive-perceptual, and sensorimotor impairments. Only
      29 studies involving 832 participants (mean age = 64.3 years) addressed these
      goals. No studies directly researched the effects of occupational therapy on
      depression after stroke. Eight studies addressed cognitive-perceptual abilities.
      The findings indicated that homemaking tasks resulted in greater improvement of
      cognitive ability than paper-and-pencil drills and that tasks that forced
      awareness of neglected space, including movement of the opposite limb into that
      space, improved unilateral neglect. Fifteen studies examined the effect of
      occupational therapy on various motor capacities after stroke. Coordinated
      movement improved under these conditions: (a) following written and illustrated
      guides for movement exercises, (b) using meaningful goal objects as targets, (c)
      practicing movements with specific goals, (d) moving both arms simultaneously but
      independently, and (e) imagining functional use of the affected limb. Research on
      inhibitory splinting was inconclusive. Based on these few studies and lack of
      replication, we could make only tentative recommendations for practice. Further
      definitive research is needed.

PMID- 12058516
TI  - Factors related to evidence-based practice among U.S. occupational therapy
      clinicians.
AB  - OBJECTIVE: The purpose of this study was to examine how U.S. occupational
      therapists access and use clinically relevant research results. METHOD: During
      the spring of 2000, 209 clinically practicing occupational therapists who were
      members of the American Occupational Therapy Association responded to a survey
      (58% response rate). The distribution of opinions and self-reported behavior was
      portrayed by descriptive statistics, and chi-square cross-tabulations and Pearson
      correlation coefficients were calculated between demographic and evidence-based
      practice variables. RESULTS: Respondents occasionally accessed research
      information through a variety of resource media. The majority (57%) implemented
      between one and five new, research-based treatment plans in the past year.
      Compared with respondents with less experience, a greater proportion of
      respondents with 15 or more years of clinical experience did not believe that
      research conclusions usually translated into treatment plans for individual
      clients (chi 2 = 20.620, p < .01). Almost three fifths (59%) of respondents
      reported that time was provided on the job to attend continuing education;
      however, 45% strongly disagreed that time was available at work to access
      research information. Other reported barriers to research utilization included
      lack of time on the job, high continuing education costs, weak research analysis
      skills, and placing higher value on clinical experience than on research.
      CONCLUSIONS: These findings suggest that therapists are currently engaging in a
      modest amount of evidence-based practice. Removing the barriers identified in
      this study may increase research utilization among clinicians.

PMID- 12058517
TI  - Doing-being-becoming: occupational experiences of persons with life-threatening
      illnesses.
AB  - OBJECTIVE: Life-threatening illness profoundly affects people's occupational
      functioning, yet continuing occupational engagement seems vital to their well
      being. This qualitative study used a doing-being-becoming framework to explore
      the place of occupation in human lives threatened by illness. METHOD: The
      experiences of 13 male and 10 female day hospice participants were investigated
      through a combination of focus groups, individual interviews, and participant
      observation. These data were interpreted by a process of constant comparison,
      coding, and theme building. RESULTS: Experiences of doing were evident in
      accounts of losing and maintaining valued occupations and striving to preserve
      physical and mental functioning. A sense of being through occupational engagement
      arose in social relationships and self-exploration that enhanced feelings of self
      worth. Occupation promoted the experience of becoming by providing fresh learning
      opportunities and a sense of contributing to others' welfare. CONCLUSION: The
      data offer new insights into the potential benefits of occupational engagement
      for persons dealing with life-threatening illnesses. Use of the doing-being
      becoming framework enriched analysis of these data, which, in turn, have
      contributed to the understanding of the framework's theoretical concepts.

PMID- 12058518
TI  - The school as social context: social interaction patterns of children with
      physical disabilities.
AB  - OBJECTIVE: The purpose of this study was to investigate the characteristics of
      the school social environment experienced by children with physical disabilities
      and the social interactional characteristics of children with physical
      disabilities in the school environment. The goal was to understand the
      interactive processes that support or inhibit these children's social
      interactions. METHOD: Naturalistic observation and participant interviews were
      used to collect data on social interaction patterns of three children with
      physical disabilities 5 to 8 years of age who were enrolled in age-appropriate
      regular education classrooms. Descriptive codes were obtained through constant
      comparative analysis. RESULTS: Four themes were identified that characterized
      aspects of the social environment affecting the social interactions of children
      with disabilities: reciprocity, characteristics of social and play interactions,
      effects of adult involvement, and quality of occupational engagement. CONCLUSION:
      The study supports the need for occupational therapists to focus intervention on
      multiple aspects of the social environment to facilitate children's
      socialization.

PMID- 12058519
TI  - Multisensory approach to handwriting remediation: perceptions of school-based
      occupational therapists.
AB  - OBJECTIVE: The purpose of this study was to describe the current practices of
      school-based occupational therapists regarding their use of multisensory
      modalities and activities in handwriting remediation. METHOD: A survey was sent
      to 313 school-based occupational therapist members of the American Occupational
      Therapy Association who identified themselves as working in a school system as
      their primary employment setting. Of these, 198 surveys were returned and
      analyzed descriptively, resulting in a response rate of 63.3%. RESULTS: More than
      130 different multisensory modalities and activities were documented. Twenty-five
      of these had previously been reported in the literature, the other 114 were
      documented, by respondents, within the "other" category. Most respondents
      reported using 5 or more modalities and activities per student, the most frequent
      being chalk and chalkboard. No consensus among respondents is apparent about the
      primary sensory systems stimulated by the modalities and activities. No
      difference in modality and activity use was found on the basis of demographic
      variables. CONCLUSION: Overall findings indicate that the breadth of modalities
      and activities being used is far greater than that currently found in the
      literature. The results suggest a need for completing studies designed to examine
      the use and effectiveness of multisensory modalities and activities in
      handwriting remediation.

PMID- 12058520
TI  - The process and outcomes of a multimethod needs assessment at a homeless shelter.
AB  - Many factors contribute to homelessness, including extreme poverty, extended
      periods of unemployment, shortages of low-income housing, deinstitutionalization,
      and substance abuse. As a result, the needs of people who are homeless are broad
      and complex. This needs assessment used literature reviews, review of local
      documents and reports, participant observation, locus groups, and reflective
      journals to guide the development of an occupational performance skills program
      at one homeless shelter in south Florida. Through these methods, the role of
      occupational therapy was extended beyond direct service to include program and
      resource development, staff education, advocacy, and staff-resident mediation.
      The findings of the needs assessment and the actions taken as a result of this
      work point to the huge potential for occupational therapists and students to work
      together with staff and residents of homeless shelters.

PMID- 12058522
TI  - Research productivity among occupational therapy faculty members in the United
      States.
AB  - The purpose of this study was to examine the current research performance
      patterns of occupational therapy faculty, identify factors that influence
      individual faculty members productivity, and compare current faculty research
      performance with earlier studies in occupational therapy. Survey questionnaires
      from 158 faculty members were analyzed. Compared to earlier data, the results
      showed that today's occupational therapy faculty members have obtained higher
      degrees, published more refereed articles, acquired larger external grants,
      stayed in academia longer, and developed clinical specialty areas. Tenured senior
      faculty members spent more time on research-related tasks, produced more
      publications and grants, and perceived institutional factors as more favorable
      for research than did untenured faculty in lower ranks. The overall enhancement
      in productivity among occupational therapy faculty members in the 1990s suggests
      an increase in academic scholarly activities.

PMID- 12058521
TI  - A health education program for elderly persons with visual impairments and
      perceived security in the performance of daily occupations: a randomized study.
AB  - OBJECTIVE: The purpose of this randomized, longitudinal study was to investigate
      the impact of a health education program on perceived security in the performance
      of daily occupations 4 months after the intervention period. METHOD: Two groups
      of persons with age-related macular degeneration were compared: Those who had
      followed a newly developed health education program that was based on occupation
      and those who took part in a standard individual intervention program. RESULTS:
      Significant differences in the level of perceived security between the groups
      were found for 13 of 28 occupations. Participants in the health education group
      maintained or improved their level of perceived security in 22 daily occupations,
      whereas those in the individual intervention group declined to a lower level in
      17 daily occupations. CONCLUSION: This study provides support for the
      effectiveness of the health education program to enhance security and hinder a
      progressive decline in perceived security in daily occupations.

PMID- 12058523
TI  - Evaluating the effectiveness of occupational therapy faculty development
      workshops.
AB  - OBJECTIVE: The purpose of this study was to evaluate, from the participants'
      perspective, the effectiveness over time of 10 occupational therapy faculty
      development workshops conducted between 1994 and 1998. METHOD: Surveys were
      mailed to 179 occupational therapy faculty participants to gather demographic
      data and perceptions of the following aspects of the workshops: benefits over
      time of the instructional content, changes made in current teaching practices,
      progress as a faculty member, and future needs for faculty development. RESULTS:
      The response rate was 63% (n = 106). The majority (72%) of respondents had less
      than 5 years of teaching experience. Respondents were women in their early 40s
      with approximately 12 years of clinical experience and a master's degree.
      Respondents perceived the most effective aspect of the faculty development
      workshops as the opportunity to participate in a face-to-face environment in
      which they observed the skills of a master teacher demonstrating instructional
      principles. Further, respondents reported that the greatest changes in their
      current teaching practices occurred in their ability to design, implement, and
      evaluate a course of instruction, thus increasing their perceptions of progress
      as a faculty member. CONCLUSION: The 10 faculty development workshops conducted
      between 1994 and 1998 were judged effective by occupational therapy faculty
      members who perceived that their participation resulted in benefits over time to
      their current teaching practices.

PMID- 12058524
TI  - Issues surrounding the use of the Internet for data collection.

PMID- 12058525
TI  - AOTA's Evidence-Based Literature Review Project: an overview.

PMID- 12058526
TI  - Occupation in stressful times.

PMID- 12058527
TI  - The quest of dreams and nightmares: my personal OT career and mental illness.

PMID- 12058528
TI  - [Effect of serotonin on differentiation of neurons producing vasoactive
      intestinal polypeptide in the rat suprachiasmatic nucleus].
AB  - This study was aimed to evaluate the morphogenetic influence of serotonin on the
      differentiating vasoactive intestinal polypeptide (VIP) neurons of the
      suprachiasmatic nucleus (SCN) in rats. The comparative morpho-functional analysis
      of VIP neurons was made in adult rats which developed under normal metabolism of
      serotonin or in its deficiency. The serotonin deficiency was induced in foetuses
      by injections of p-chlorophenilalanine to pregnant mothers. Control rats received
      the saline. According to our data, there was no difference in the VIP mRNA
      concentration and most probably in VIP synthesis in the SCN in adult rats
      following prenatal serotonin depletion compared to the control. However, the
      serotonin deficiency resulted in increase of the VIP concentration in cell bodies
      and of the VIP neurones number. The size of the VIP-neurones did not change in
      pharmacologically treated rats compared to the controls showing no functional
      hypertrophy of the neurones as a result of the activation of specific syntheses.
      From the above data, it follows that serotonin provides an imprinting influence
      differentiating the VIP neurones, contributing most probably to development of
      the VIP release mechanism.

PMID- 12058529
TI  - [Changes in structure and metabolism in the m. vastus lateralis in monkeys after
      a space flight].
AB  - Monkeys developed a significant reduction in size of the m. vastus lateralis'
      fast and slow fibres, the amount of protein in them remaining the same.

PMID- 12058530
TI  - [Analysis of the segmental structure of EEG alpha-activity in humans].
AB  - Phasic organisation of human EEG alpha activity was studied in a pilot
      investigation using a previously suggested EEG segmental analysis methodology.
      The EEG was recorded in three normal subjects under resting conditions. The
      segmentation procedure enabled effective identifying of the periods with
      different amplitude in alpha band and the short-term transitions between them.
      Mean intersegmental variability of amplitude envelope were computed for the eyes
      closed and eyes open EEG in each of 16 standard derivations. Analysis of segment
      amplitude distributions showed that the difference between the average alpha
      activity amplitude in these conditions were determined mainly by variations in
      the number of segments of different amplitude classes and not by a shift of the
      distribution or by change of its width. Distribution and quartile analysis of
      mean segment amplitudes provide evidence for possible functional heterogeneity of
      upper and middle subranges of the amplitude range.

PMID- 12058531
TI  - [Instantaneous alteration of the dog heart contractility under instantaneous
      change in the stimulation rhythm].
AB  - Isolated canine heart has an expressed ability for an instantaneous alteration in
      the sense of re-tuning, of contractility (of the speed of mechanical restitution
      in diastolic period) under instantaneous change of stimulation rhythm.
      Postextrasystolic potentiation reflects instantaneous rising of the speed of
      mechanical restitution under the influence of extrasystole in the condition of
      instantaneous transition to a higher rhythm. Depression of contractility reflects
      instantaneous decreasing of the speed of mechanical restitution under the
      influence of delayed stimulus in the condition of instantaneous transition to a
      slower rhythm. Alteration (re-tuning) of heart contractility occurred
      irrespective of the influence of neurohumoral factor and Frank-Starling law on
      the work of the heart. Alteration (re-tuning) of contractility occurs at an organ
      (cell) level.

PMID- 12058532
TI  - [Regulation of smooth muscles of the vascular wall in the rabbit pulmonary
      artery].
AB  - The cholinergic, histaminergic and adrenergic features of regulation of the small
      muscles contractile activity in a vascular wall of a pulmonary artery in rabbits
      and involvement of an endothelium in these processes, were investigated. The
      cholinergic release phenomenon of small muscles of the rabbit pulmonary artery
      has a two-component character of dose dependence. The low-threshold components of
      Pilocarpinum relaxing effect has an endothelium-dependent nature. The important
      feature of histaminergic regulation of contractile activity of segments involves
      a direct contractile effect of histamine that is not inherent. The endothelium
      renders a suppressing effect on histaminergic contraction of small muscles of the
      rabbit pulmonary artery. A basic feature of adrenergic regulation of the
      pulmonary artery involves registered-beta-adrenergic contractile effects in small
      muscles of a vascular wall. The activation of the cAMP-dependent signal system in
      small muscles of a pulmonary artery is capable of rendering a contractile effect.
      The detected features of a regulation in the small circle can have an essential
      clinical-physiological value.

PMID- 12058533
TI  - [Effect of estrogens on the coronary circulation, cardiac contractile function,
      and development of reperfusion arrhythmia].
AB  - 17-beta-estradiolsulfate (17-ES) was shown to exert a distinct vasoconstrictory
      effect on coronary vessels resulting in a decrease of the force contraction as
      well indexes of contractility. The distinct antiarrhythmic effect suggests that
      17-ES possesses some properties of calcium antagonist.

PMID- 12058534
TI  - [Effect of thyroliberin on contractility and electrical activity of isolated
      bovine lymphangions].
AB  - The role of regulatory peptides is the least explored part in the field of
      humoral regulation of lymphatics. In this paper we continue a systematic
      investigation of their effects on the lymphatic vessels of various animals. The
      effect of thyroliberin was studied on bovine mesenteric lymphatics. The isolated
      lymphatics contractility and smooth muscle cell electrical activity were
      investigated. Thyroliberin in ultra low concentrations (1 x 10(-13)-1 x 10(-18)
      M) exerts a considerable stimulating effect. The mechanism of the theroliberin
      ultra-low concentrations action and a possibility of the medical usage of the
      obtained results, are discussed.

PMID- 12058535
TI  - [Effect of interleukin-1 on lymphocyte capacity of releasing factors affecting
      platelet adhesion and aggregation, blood coagulation and fibrinolysis].
AB  - Effects of recombinant interleukin-1 (IL-1) involved an inhibition of adhesion
      and thrombocyte aggregation. In heparinised blood, the IL-1 activates production
      of protein C (PnC), alpha 2-macroglobulin (alpha 2-MG) and alpha 1-antitrypsin
      (alpha 1-AT) and facilitates formation of the fibrinolysis inhibitors. In
      fibrinolysed blood, the IL-1 suppresses production of PnC, alpha 2-MG, alpha 1
      AT, and inhibits the fibrinolysis. In a blood clot, the IL-1 suppresses
      production of PnC, alpha 2-MG, alpha 1-AT and activates the fibrinolysis.

PMID- 12058536
TI  - [Effect of Ilizarov tibial lengthening on limb blood flow].
AB  - The experiment in 23 adult dogs was based on the study of volumetric blood flow
      velocity in the superficial femoral artery and femoral vein, pulse changes in
      blood filling of the m. gastrocnemius in the conditions of tibial lengthening to
      17.5-23% from the initial length. Complex changes in the blood flow parameters
      were revealed after surgical intervention and within 7 distraction days. When the
      distraction ended, the volumetric blood flow velocity in the femoral artery was
      reduced by 19% and the blood flow out of the vessel was improved by 17%. When
      fixation was over, the volumetric blood flow velocity in the vessel increased by
      37% and the improved outflow preserved. At each experimental stage, there was an
      increased volumetric blood flow velocity in the femoral vein as compared to its
      value in the control group, its correspondence to the superficial femoral artery
      as well as similar dynamics in blood flow changes in the femoral vessels and m.
      gastrocnemius. The findings show that the vascular system of bone regeneration
      provides accelerated arterial blood transportation into the venous system during
      organotypical bone area formation.

PMID- 12058537
TI  - [Catecholamines, nitrogen oxide, and resistivity to stressor lesions: effect of
      adaptation to hypoxia].
AB  - Pronouncement of stress-induced disturbance of searching behaviour (using "open
      field" test) and stomach ulceration were compared for the first time with
      activity of the catecholamine system in hypothalamus and striatum and also with
      activity of the stress-limiting system of nitric oxide (NO) in the rats of two
      strains August and Wistar, which differ in their resistance against stress
      induced cardiovascular disorders. The effect of prior adaptation to hypobaric
      hypoxia on these disorders was also studied. August rats appeared to be more
      resistant than Wistar rats against stress-induced disturbance of the searching
      behaviour and stomach ulceration. Results of measuring the content of
      catecholamines in brain structures and the content of NO stable metabolites
      nitrate/nitrite in plasma suggested that these differences could be due to the
      stress activation of the nigro-striatal dopaminergic system in August rats, which
      was not observed in Wistar rats, and also to the higher production of NO in
      August than in Wistar rats. Adaptation to hypoxia considerably restricted these
      stress disorders in rats of both strains. Importantly, the protective effects
      were associated with activation of the nigro-striatal dopaminergic system in all
      the animals. In the result, adapted Wistar rats, as distinct from non-adapted
      Wistar rats, displayed a stress activation of this system. The protective effects
      of adaptation were also accompanied by an increased NO synthesis. Taken together,
      the data suggest an important role of the responsiveness of the brain
      dopaminergic system and NO system in the mechanism of resistance against stress
      induced disturbances.

PMID- 12058538
TI  - [Glucocorticoid hormones in immunomodulating effect of defensins].
AB  - Defensins are a family of antimicrobial cationic peptides localized mainly in
      neutrophile granulocytes. The defensins are known to display corticostatic
      activity by means of suppression of stress- and ACTH-induced rise in
      corticosterone level in the blood. The present study examines influence of
      defensin fractions with different corticostatic activity on suppressor functions
      of T-lymphocytes. It was shown that corticostatic effects of defensins are
      revealed under an increased level of glucocorticoids in the blood after
      hydrocortisone application. Defensins were found to limit the inhibitory action
      of glucocorticoids on the suppressor functions of T-lymphocytes. After
      adrenalectomy this phenomenon was not observed.

PMID- 12058539
TI  - [Effect of prostaglandin F2alpha on cells of the mammary gland alveoli in mice].
AB  - In studies on lactating laboratory mice an influence of prostaglandin F2 alpha on
      the value of transepithelial potential difference and resistance of the alveolar
      secretory epithelium in the mammary gland, was studied. Prostaglandin F2 alpha
      did not affect initial level of transepithelial potential difference and
      resistance in alveoles. In all experiments with the preliminary application of
      prostaglandin F2 alpha in different concentrations (1 x 10(-5)-1 x 10(-11) M) was
      registered a reliable increase in an amplitude (before 31 +/- 2%) and duration
      (before 43 +/- 3%) to return reactions on oxytocin. Prostaglandin F2 alpha caused
      a reduction of transepithelial resistance in the alveolar secretory epithelium of
      first phase to return reaction on oxytocin on 28 +/- 22%. The data obtained
      indicate a possibility of participation of prostaglandin F2 alpha in development
      of certain stages of shaping a composition of milk.

PMID- 12058540
TI  - [Kinetic parameters of maltose hydrolysis and glucose intake in the rat small
      intestine in a chronic experiment].
AB  - "True" (corrected for the influence of the pre-epithelial layer) kinetic
      constants of maltose hydrolysis (Km and Vmax) and Glucose active transport (Kt
      and Jmax) in the isolated loop of the rat small intestine in chronic experiments
      were determined using a new mathematical approach. The Km (4.260.25 mM) does not
      differ from that, obtained in in vitro experiments on the homogenates of mucous
      membrane taken from the same intestinal loops, and the Vmax (0.72 +/- 0.07
      mol/(min.cm)) is 1.7 times lower than that in in vitro experiments. The Kt and
      Jmax values are 3.18 +/- 0.68 mM and 0.73 +/- 0.07 mol/(min.cm), resp. The
      estimated values of Km, Kt and Vmax are in accordance with the corresponding
      published data, whereas the Jmax is several times higher than the value generally
      believed on the basis of acute experiments in vivo. A high level of glucose
      absorption in the small intestine of unanesthetized animals is achieved mainly
      due to a high permeability of the pre-epithelial layer and a high capacity of the
      active transport as a major mechanism of glucose absorption in the small
      intestine under normal conditions.

PMID- 12058541
TI  - [Effect of prednisolone on the basal gastric secretion in laboratory rats
      depending on functional state of the stomach adrenoreceptors].
AB  - Activation of the stomach adrenoreceptors with adrenaline resulting in inhibition
      of fundal glands promotes stimulating effect of prednisolone glucocorticosteroid
      action on basal gastric secretion.

PMID- 12058543
TI  - [A device for stereotaxic fixation of the animal spine].

PMID- 12058542
TI  - [Pancreatic enzyme activity in early phases of acute experimental pancreatitis in
      rats].
AB  - Experiments were performed on laboratory rats with acute pancreatitis caused by
      local freezing the pancreas with chlorethyl. An active action of enzymes alpha
      amilase, lipase, phospholipase A2, was revealed. During the first hours, an
      increase in action of all three enzymes, particularly that of phospholipase A2,
      was found. It was established that the lipid spectrum of pancreas had changed. It
      shows that cell membranes were destroyed. Experiments revealed an activating role
      of Ca2+ ions for all the enzymes and a correcting action of chlorpromasine.

PMID- 12058544
TI  - [Nikolai Vasil'evich Golikov and his contribution into development of ideas of
      the St. Petersburg University physiological school].

PMID- 12058545
TI  - Adolescent standardized patients: method of selection and assessment of benefits
      and risks.
AB  - BACKGROUND: Our psychiatric Objective Structured Clinical Examination (OSCE)
      group wishes to develop adolescent psychiatry OSCE stations. The literature
      regarding adolescent standardized patient (SP) selection methods and simulation
      effects, however, offered limited assurance that such adolescents would not
      experience adverse simulation effects. PURPOSE: Evaluation of adolescent SP
      selection methods and simulation effects for low- and high-stress roles. METHOD:
      A two-component (employment-psychological) SP selection method was used.
      Carefully selected SPs were assigned across three conditions: low-stress medical
      role, high-stress psychosocial role, and wait list control. Qualitative and
      quantitative measures were used to assess simulation effects. RESULTS: Our
      selection method excluded 21% (7% employment and 14% psychological) of SP
      applicants. For SP participants, beneficial effects included acquisition of job
      skills and satisfaction in making an important contribution to society. SP
      reactions of discomfort to roles were reported. Long-term adverse effects were
      not identified. CONCLUSIONS: A two-component adolescent SP selection method is
      recommended. Adolescent SP benefits outweigh risks.

PMID- 12058546
TI  - A qualitative assessment of 1st-year internal medicine residents' perceptions of
      evidence-based clinical decision making.
AB  - BACKGROUND: Residents' perceptions about evidence-based clinical decision making
      remain largely unexplored. PURPOSE: To understand how residents perceive and use
      evidence-based medicine in clinical decision making. METHODS: Qualitative study
      using a semistructured questionnaire and focus group in a postgraduate training
      program in internal medicine at an academic U.S. medical center. Seventeen 1st
      year internal medicine residents in their 1st postgraduate year were interviewed.
      Six additional 1st-year residents formed a validation group. RESULTS: The
      interplay of time and expertise modified how physicians-in-training incorporate
      evidence into clinical decision making. When time was available, the residents
      preferred to answer their questions by searching and critically appraising the
      literature. This "self-acquired" expertise empowered them to help patients by
      using participatory decision-making styles. When time was limited, the residents
      turned to experts. Residents assumed that experts practiced evidence-based
      medicine. This "borrowed" expertise was thought to be the most efficient way of
      integrating evidence and clinical expertise, but it led to the use of a parental
      style when answers were taken back to the bedside. CONCLUSION: The practice of
      evidence-based medicine empowers 1st-year residents and appears to affect their
      choice of decision-making style. Further research is needed to better understand
      the link between decision-making style and evidence-based medicine.

PMID- 12058547
TI  - Volunteer faculty: what rewards or incentives do they prefer?
AB  - BACKGROUND: Clerkship directors and college administrators have concerns about
      recruitment and retention of practicing physicians for volunteer teaching. There
      is a paucity of data regarding the rewards and incentives offered to, or desired
      by, the nonsalaried community-based practicing physicians who volunteer their
      time to teach. PURPOSE: This study was designed to gain information about rewards
      and incentives from volunteer teachers in pediatric, family practice, and
      internal medicine clerkships. METHODS: We surveyed nonsalaried physician teachers
      of internal medicine, family medicine, and pediatrics across the United States.
      The survey focused on teachers' evaluation of the rewards or incentives offered
      by the programs in the following categories: educational opportunities, services
      or gifts, recognition bestowed by the school, academic appointments, and monetary
      payments. Respondents rated each item from 1 (not appreciated) to 5 (very much
      appreciated). They also were asked to rank order the rewards or incentives (with
      the addition of a category of personal satisfaction) from 1 (least appreciated)
      to 6 (most appreciated). RESULTS: Educational opportunities received high
      ratings, especially when the school bore the cost of providing a service. Payment
      for teaching was offered to 37% of the respondents, and those who were paid rated
      it higher. Overall, payment for teaching had a mean appreciation score of 3.94,
      second only to travel and meeting registration reimbursement (4.27). However, in
      the rank order listing, personal satisfaction had the highest rank (5.16). In
      contrast, payment for teaching (2.92) and gifts or services from the college
      (2.53) were at the bottom of the rank order. CONCLUSION: The survey asked
      practicing physicians the value they placed on awards and incentives provided to
      them by the college. This information should help administrators and clerkship
      directors in recruiting and retaining community-based practicing physicians for
      teaching.

PMID- 12058549
TI  - Commentary on "review criteria for research manuscripts".

PMID- 12058548
TI  - Clinical performance assessment and interactive video teleconferencing: an
      iterative exploration.
AB  - BACKGROUND: The direct observation of students in authentic settings by faculty
      provides valuable feedback on performance and helps ensure mastery of clinical
      skills. DESCRIPTION: We explored the use of interactive video technology (IVT) as
      a way of involving community preceptors as raters on a clinical performance exam
      for 3rd-year students after their family medicine clerkship. Family medicine
      preceptors, from locations in their communities, observed students on campus
      conduct interviews and physical exams of standardized patients and then
      interacted with them during their case presentations. EVALUATION: We chose an
      action research approach to this project and conducted four independent trials.
      Interviews and observations were structured around three areas of concern: human,
      technical, and institutional. CONCLUSIONS: We feel confident in recommending IVT
      as a viable option for involving community preceptors in high-stakes testing and
      with other campus-based activities. We also report on the value of IVT in faculty
      development activities.

PMID- 12058550
TI  - Faculty views of reimbursement changes and clinical training: a survey of award
      winning clinical teachers.
AB  - BACKGROUND: Prominent authorities believe that managed care and governmental
      policies are compromising the clinical education of future physicians. PURPOSE:
      This study sought the views of clinical teachers to quantify the extent to which
      managed care and governmental policies have changed clinical education. METHODS:
      Questionnaires were mailed to faculty that U.S. medical schools had recognized
      for clinical teaching excellence. Measures included reports of change in quality
      of clinical teaching due to payment regulations, Liaison Committee on Medical
      Education (LCME) and Residency Review Committee (RRC) requirements, and
      institutional support for teaching; change in numbers of students-trainees in
      clinics; need to generate more clinical revenue; and change in enjoyment of
      teaching. Other measures about clinical teaching included faculty attitudes,
      institutional rewards, and teaching different levels of students. Characteristics
      of the respondents also were measured. RESULTS: Faculty reported that payment
      regulations have affected clinical teaching negatively and that faculty need to
      generate more clinical revenue. Institutions tend to provide a supportive
      teaching environment but do not reward teaching financially. Intrinsic incentives
      for teaching increase as the level of student increases. Faculty reports did not
      differ by medical specialty or other faculty characteristics. Differences among
      medical schools occurred on all measures. CONCLUSIONS: Clinical education is
      being negatively affected, but not yet critically. Continued clinical financial
      pressures on faculty will affect all levels of clinical education, particularly
      for medical students. Differences among institutions indicate that individual
      schools can moderate or exacerbate the impact of external forces on the teaching
      faculty. Medical schools should monitor increasing pressures on faculty and
      ensure that goals, processes, support, and rewards for clinical teaching are
      proportionate to those for clinical care.

PMID- 12058551
TI  - Evaluations of clinical faculty: the impact of level of learner and time of year.
AB  - BACKGROUND: Because of the importance of faculty evaluation data for faculty
      development, promotion, reappointment, and remuneration, the quantity and
      characteristics of evaluation data need study. PURPOSES: To examine differences
      in evaluation ratings according to level of learner (student vs. resident) and
      time of year. METHODS: Retrospective analyses of 1,281 faculty evaluations
      provided for 132 faculty over a 12-month period by students and residents on
      inpatient medicine rotations. RESULTS: Faculty had an average of eight
      evaluations over a year. Students gave more favorable ratings than residents.
      Over the year, students became less critical and residents became more critical.
      Winners of teaching awards had better evaluations than other faculty. Standard
      errors around mean ratings for an individual faculty member were approximately
      0.25 on a 4-point scale. CONCLUSIONS: The profile and precision of assessments
      for an individual will vary based on the number, timing, and source of ratings.
      Decisions based on similar data should be made with caution.

PMID- 12058552
TI  - Medical students' perspectives on and responses to abuse during the internal
      medicine clerkship.
AB  - BACKGROUND: The abuse of medical students on clinical rotations is a recognized
      problem, but the effects on students and their responses warrant further study.
      PURPOSE: To determine the severity of student abuse and the effects of abuse on
      students during the internal medicine clerkship. METHODS: Internal medicine
      clerks at 11 medical schools (N = 1,072) completed an exit survey. Students were
      asked whether they had been abused. If they had, they were asked about the
      severity of the abuse, whether they reported it, and its effects on them.
      RESULTS: Of the responding students, 123 (11%) believed they had been abused.
      Only 31% of the students who felt abused reported the episodes to someone. The
      most common consequences of the events included poor learning environments, lack
      of confidence, and feelings of depression, anger, and humiliation. CONCLUSION:
      Students described a variety of personal and educational effects of abuse. They
      generally did not report abuse because of fear of retaliation and the belief that
      reporting is pointless.

PMID- 12058553
TI  - Review, deliberation, and voting: a study of selection decisions in a medical
      school admission committee.
AB  - BACKGROUND: Medical school admission committees differ in their decision-making
      procedures. Some assign ratings to groups of application materials to devise rank
      order acceptance lists, whereas others deliberate and vote on each separate
      application. PURPOSE: This study examined what the screening review and
      deliberative processes contribute to decision making in a medical school
      admission committee. METHODS: We reviewed records of admission committee members'
      preliminary votes on applicants after initial screening, final votes after
      committee deliberation, and written comments regarding issues of concern
      influencing their votes cast. Descriptive univariate and bivariate analyses are
      presented. RESULTS: Approximately one in five votes cast after initial screening
      was changed following committee deliberation, resulting in majority vote shifts
      in roughly 10% of cases containing votes by the same committee members at both
      time periods. Factors cited as influencing vote changes (in declining order of
      frequency) included Medical College Admission Test scores, medical experience,
      comparison with other applicants, grades, letters of evaluation, interviews,
      individual attributes, residency status, service experience, expressed desire of
      committee members to discuss the applicant at the meeting, American Medical
      College Application Service personal statement, and diversity. CONCLUSIONS:
      Admission committee members' voting behaviors appear to be influenced by the
      deliberative process. Future studies should explore the extent to which committee
      group dynamics influences decision making and the relative contribution of
      particular academic and nonacademic factors to vote-changing behavior.

PMID- 12058554
TI  - [Viral seroprevalence, transfusion and alloimmunization in adults with sickle
      cell anemia in Guadeloupe].
AB  - We retrospectively studied the prevalence of anti HIV 1 and 2, anti-HTLV-I, anti
      Hepatitis B and C viruses (HBV and HCV) antibodies, anti-HBV vaccinal coverage,
      transfused patients and alloimmunizations frequencies among adult sickle cell
      patients attending the sickle cell center (SCC) of Guadeloupe. The data were
      collected from the medical files of the centre. Among the studied samples (n =
      331) no transfusional HIV contamination was observed. All patients with HTLV-I (n
      = 11, 3.3% of whole sample) and anti-HCV (n = 9, 2.7%) positive serology had
      transfusion history. Five patients (1.5%) had an active hepatitis B. Vaccination
      against HBV efficiently protected 247 patients (74.4%) and 57 had post-hepatitis
      B antibodies. We observed that 213 patients (64%) had a history of transfusion
      (88% of SS patients and 36% of the SC patients, p < 0.05). Fifty-four patients
      (16%) presented alloimmunization, 4 of them have never been transfused. These
      results show that it is still necessary to optimise transfusion protocol and
      their safety, and to diagnose viral contamination in transfused sickle cell
      patients.

PMID- 12058555
TI  - Recombinant forms of Gerbich blood group antigens: expression and purification.
AB  - Recombinant forms of normal glycophorin C (GPC), carrying the high frequency
      Gerbich blood group antigens, and its natural deletion mutants of Yus and Ge type
      (all combined with oligohistidyl tag) were expressed in CHO and COS 7 cells. The
      stable expression of all recombinant forms of GPC in CHO cells was obtained, but
      the level of expression was low and detectable only by flow cytometry. The high
      level of transient expression of GPC recombinant forms in COS 7 cells allowed
      their purification on Ni-NTA-agarose. The purified recombinant GPC and mutants of
      Yus and Ge type behaved in SDS-PAGE similarly to normal GPC forms from RBC
      membranes. The recombinant GPC.Yus and GPC.Ge mutants appeared as diffuse bands,
      suggesting the similar heterogeneity of glycosylation that was observed in
      natural GPC.Yus and GPC.Ge glycoproteins. The flow cytometry analysis of the
      transfected CHO and COS 7 cells showed that binding of anti-GPC monoclonal
      antibodies to GPC variants was accordant with the known fine specificity of these
      antibodies. The obtained recombinant forms of GPC carrying common Gerbich
      antigens may be useful in serology, and also as model molecules for structure
      function studies.

PMID- 12058556
TI  - Declared hepatitis C screening strategies in blood recipients in French
      hospitals.
AB  - AIMS OF THE STUDY: In spite of official recommendations and measures in France,
      screening strategies of hepatitis C performed in the field of transfusion are not
      clearly known. The aim of this study is to describe the screening strategies
      before and after the current year of the transfusion in blood recipients in
      several French medical departments and hospitals. MATERIALS AND METHODS: A
      qualitative study using the key informant technique was carried out. A sample of
      179 departments and 64 hospitals in charge of patients transfused with low or
      high-volumes of homologous blood products was constituted. The key informants
      were asked about the number of homologous blood products, the number of
      recipients transfused in the hospital, the volume of transfusion performed, the
      existence of a single defined screening strategy, the time of prescription of the
      biological tests (before or after transfusion), the tests performed on
      cryopreserved blood samples, and the indications of the transfusion. RESULTS: The
      main screening strategy was HCV serology (second or third generation of enzyme
      immunoassays) with transaminase assessments before and after transfusion in 14%
      of the declared screening strategies. Screening tests were more frequently
      prescribed after transfusion, in at least 64% of the declared screening
      strategies according to the volume of transfusion. HCV serology was the common
      test prescribed in 61 and 50% of the screening strategies for low and high-volume
      transfusion respectively. The screening strategies showed a large heterogeneity
      combining HCV serology, transaminase assessment, before or after transfusion.
      CONCLUSION: A great heterogeneity of screening strategies was found. The most
      frequent was HCV serology with transaminase assessment before and after
      transfusion. Recommendations on screening strategies are needed in order to limit
      practice heterogeneity. This study will help building a cost-efficacy model in
      order to guide public health decision making.

PMID- 12058557
TI  - [Creation and organization of a mobile collection unit].
AB  - In France, nearly eighty per cent homologous blood donations are given in mobile
      settings. The collection site requirements, and particularly premises, are
      conditioning the security of persons, blood products quality, and blood
      collection efficiency. They also take a decisive part in the public image of the
      transfusion network. This paper describes an easy method for evaluating and
      validating premises used for mobile setting of blood collection.

PMID- 12058558
TI  - [Biovigilance, a vigilance exercised on the utilization of products obtained from
      the human body].
AB  - Organ transplantations and tissue/cells grafts are efficacious in many diseases.
      Nevertheless, beside the risk due to the technology which permits to carry out
      transplantations and grafts (surgery, tissue and cells collection, preservation,
      storage, cell expansion technics, immunosuppressive regimen,...), the
      microbiology risk must be controlled throughout the process leading to the
      transplantation or the graft. The structures, the organizations, the procedures,
      the information network and the controls assure the control of the risk. It is
      the main objective of human product vigilance. Future regulations will define the
      objectives of this sanitary vigilance more precisely.

PMID- 12058559
TI  - Red carpet, white lilies: love of death in the poetry of the Jewish underground
      leader Avraham Stern.

PMID- 12058560
TI  - Anorexia, masochism, self-mutilation, and autoerotism: the spider mother.
AB  - In summary, both self-mutilators and eating-disordered individuals come from
      dysfunctional homes with a very controlling mother and usually absent father.
      They often have a history of trauma. They are depressed and obsessive, attached
      to their mothers, who discourage attempts at emancipation. The symptoms serve the
      purpose of keeping them as little girls with negative feelings toward
      menstruation, sexual maturity, development, and femininity in general. These
      symptoms comprise self-destructive behavior in the service of removing sexual
      thoughts, temptation, and activities. Favazza (1987) included both eating
      disorders and self mutilation in his "deliberate self-harm syndrome." The
      symptoms, whether they be anorexic, bulimic, or a form of self-mutilation are
      seen as "autoerotic in nature and a substitute for normal masturbation" (Hull &
      Lane, 1988). Eating disorders and delicate self-mutilation are said to have "a
      cathartic, self-purifying, function in that they modulate states of anxiety,
      sexual tension, anger or dissociated emptiness, and they bring about a tremendous
      quasi-physical sense of relief" (Cross, 1993, p. 50). These patients' use of
      substitutes prevents maturation and growth as women, causing regression to
      pregenital phases with the use of pregenital defenses, and the demise of the
      demands of puberty and mature sexuality.

PMID- 12058561
TI  - Origin and nature of the great illusion: an introduction to and translation of
      Shankara's analysis of transference.

PMID- 12058562
TI  - Narcissistic revenge and suicide: the case of Yukio Mishima. Part II.

PMID- 12058563
TI  - Through the unknown, remembered gate: journeys into the labyrinth.

PMID- 12058564
TI  - Canadian veterinarians asked to participate in national disease surveillance of
      neosporosis, Johne's disease, bovine leukosis, and bovine viral diarrhea.

PMID- 12058565
TI  - An ethicist's commentary on the case of the company offering a rebate if the
      veterinarian changes vaccines.

PMID- 12058566
TI  - The veterinary drugs directorate to discuss extra-label drug use in Halifax.

PMID- 12058568
TI  - Rickettsial infection in farmed Atlantic salmon in eastern Canada.
AB  - The cause of death in a postsmolt, Atlantic salmon population with elevated
      levels of mortalities was investigated. Diagnosis of a rickettsia-like organism
      was based on gross pathology, histopathology, differential staining, electron
      microscopy and fluorescent antibody tests. The course of the infection and
      response to treatment are discussed. This is the first reported occurrence of
      salmon rickettsias in the Atlantic coast of North or South America.

PMID- 12058569
TI  - Preliminary assessment of the risk of Salmonella infection in dogs fed raw
      chicken diets.
AB  - This preliminary study assessed the presence of Salmonella spp. in a bones and
      raw food (BARF) diet and in the stools of dogs consuming it. Salmonella was
      isolated from 80% of the BARF diet samples (P < 0.001) and from 30% of the stool
      samples from dogs fed the diet (P = 0.105). Dogs fed raw chicken may therefore be
      a source of environmental contamination.

PMID- 12058570
TI  - Salmonella Muenster infection in a dairy herd.
AB  - The overall purpose of this study was to provide information on animal and
      occupational health associated with the infection of a diary herd with Salmonella
      Muenster that would be useful in the management of dairy herds so infected. This
      retrospective, longitudinal report records a 2-year infection of a 140-cow dairy
      herd with S. Muenster, which was likely introduced by additions to the herd. Six
      cows aborted or had diarrhea due to salmonellosis in the last trimester of
      pregnancy. Additions to the herd and the presence of animals that had not
      received an Escherichia coli bacterin-toxoid were risk factors for salmonellosis.
      One neonate died, and 24 of 36 calves born between November 1998 and May 1999 had
      diarrhea by 1 mo of age. Initially, over 60% of the cows were fecal positive;
      within 6 months, all cows but I had become infected. The intermittent shedding of
      the organism and the eventual zero prevalence highlight the inappropriateness of
      extensive culling as an eradication strategy. Cultures of the bulk-tank milk
      filters were more sensitive than cultures of the bulk-tank milk samples at
      detecting S. Muenster. Two months after the index case, S. Muenster was cultured
      from the milk of 7.8% of the cows. Positive fecal or milk cultures were not
      associated with impaired health or production. The herd's milk was a zoonotic
      risk, but contact with infected animals was not. The organism spread easily
      between operations, likely via manure-contaminated clothing and footwear.

PMID- 12058571
TI  - A bulk tank milk survey of Ostertagia ostertagi antibodies in dairy herds in
      Prince Edward Island and their relationship with herd management factors and milk
      yield.
AB  - The objective of this study was to quantify the relationship of the levels of
      antibodies to Ostertagia ostertagi in bulk-tank milk samples from Prince Edward
      Island (PEI) dairy farms to milk production and to herd-management practices
      potentially related to gastrointestinal nematode infections. The milk samples
      were obtained from 289 to 322 dairy farms during 2000; production and management
      data were available from 197 and 200 farms, respectively. Cow exposure to pasture
      and whole-herd anthelmintic treatment were the only herd management variables
      significantly associated with antibody levels in the fall of 2000. An increase in
      antibody levels from the observed 25th percentile to the 75th percentile
      (interquartile range) was associated with a drop in milk production of 1.2
      kg/cow/day. The results of this study indicate that the enzyme-linked
      immunosorbent assay for O. ostertagi antibody is a potentially useful technique
      to measure parasite exposure in adult dairy cows and that parasite burdens in
      lactating cattle in PEI have an important impact on milk production.

PMID- 12058572
TI  - Prevention of pregnancy in the dog with a combination of prostaglandin F2 alpha
      and bromocriptine.
AB  - Fifteen mated bitches were given prostaglandin F2 alpha (PGF2 alpha) [250
      micrograms/kg body weight] and bromocriptine (10 micrograms/kg BW) twice daily
      from days 6 to 10 of diestrus. Progesterone concentrations declined during
      treatment. None of the bitches whelped. Daily treatment with PGF2 alpha and
      bromocriptine for 5 d appears to induce luteolysis and prevent early pregnancy.

PMID- 12058573
TI  - Eosinophilic gastroenteritis in a dog.
AB  - A 9-year-old mixed-breed dog was evaluated for chronic intermittent vomiting,
      hematemesis, and melena lasting several months. Biopsy specimens obtained during
      exploratory laparotomy revealed eosinophilic gastroenteritis. Treatment included
      drug therapy to reduce gastrointestinal inflammation and dietary management to
      limit antigenic exposure.

PMID- 12058574
TI  - Hepatocellular carcinoma and suspected splenic hemangiosarcoma in a potbellied
      pig.
AB  - A 10-year-old, lethargic, potbellied pig presented with signs of abdominal
      discomfort and a palpable abdominal mass. Laparotomy revealed a 20 cm diameter
      mass on the spleen and smaller masses on the omentum and liver. After euthanasia
      and histologic examination of the hepatic mass, the diagnosis was hepatocellular
      carcinoma.

PMID- 12058575
TI  - The evolving workplace for new veterinary graduates.

PMID- 12058577
TI  - A theory on the evolution of the habitual orthograde human bipedalism--the
      "Amphibische Generalistentheorie".
AB  - The theory is formulated that ubiquitous scarcity of energy is one of the main
      motors of evolution. It is concluded that our primate ancestors never came down
      from the trees, but rather they have always been (semi-)terrestrial. This habit
      is probably an old symplesiomorph trait, older than primates themselves.
      Terrestrial habits in primates correlate to body weight in small systematic
      groups (e.g., large genera, families) but are, overall, completely independent
      from individual body mass. An omnivorous, semiterrestrial quadrupedal locomotor
      generalist seems to be the most probable morpho- and eco-type for our ancestor at
      the threshold of a hominoid stage of our evolution. The theory presented here
      suggests that our hominoid ancestor lived in gallery forests and changed strata
      in order also to inhabit the savannah habitat as well as the shallow water of the
      rivers or coasts. Foraging in a wading manner was extremely favourable for an
      effective and, especially, seasonally independent, animal protein supply.
      Anatomical adaptations to orthogradism and proportions of the extremities are
      discussed in relation to the necessary and frequent change of habitat strata.
      Ultimately, human bipedalism is seen here to be derived as a consequence of the
      centre of body mass, which is, in primates, near the hind extremities. By
      contrast to other mammals entering the water, wading primates sink back on their
      hind limbs. Selective forces for habitat use, limb proportions and wading habits
      are discussed, as well as the phylogenetic origin of human affinity to water and
      shores in all peoples through all times, from australopithecine times through the
      Paleolithic until today.

PMID- 12058576
TI  - Diagnosing rupture of the cranial cruciate ligament.

PMID- 12058578
TI  - Pneumatized spaces, sinuses and spongy bones in the skulls of primates.
AB  - The earliest attempts to understand the "pneumatized spaces" in the skulls of
      primates in general were focussed on the hollow spaces and the epithelium which
      covers their surfaces. More recent approaches consider the sinuses as a means to
      optimise skull architecture. Still, many attempts to get hold of the meaning of
      the intriguing pneumatized spaces circle around the air filled volumes they
      enclose. Here, we would like to reverse the approach and focus our biomechanic
      interpretation on the walls surrounding the big, empty, or at least not
      mechanically resistant spaces, and their mechanical properties. As a working
      hypothesis, we consider not only the walls of the more or less closed cavities,
      or sinuses, but also the braincase, the orbits, and the nasal channel as thin
      walled shells of which we know that they can carry surprisingly large loads with
      a minimum of material. Details of the wall's profiles fit with this approach.
      From the same viewpoint, the bubble-like, air-filled cavernous systems in the
      ethmoid or temporal bones, and the marrow-filled spongy substance in the upper
      jaw are looked at as honeycomb-structures, which provide mechanical properties
      that are biologically advantageous and allow the saving of weight.

PMID- 12058579
TI  - [Human races and the problem of variability--a recommendation for the solution by
      Franz Weidenreich].
AB  - In parts of anthropology race concepts were playing a central role for
      evolutionary reconstruction as a means for assessment and study of human
      variability. This method was criticised already quite early. In this paper the
      arguments of one of those early critics, Franz Weidenreich, are introduced and
      reconstructed on a methodological basis. While avoiding race concepts, Franz
      Weidenreich developed other methods for reconstructing lines of evolutionary
      development. He suggested to use an extended concept of physical constitution.
      This concept is also introduced and studied with reference to its methodological
      foundations.

PMID- 12058582
TI  - [Chronic renal insufficiency. Physiopathology and perspectives of treatment].

PMID- 12058583
TI  - Mouse genetic models to explore the function of IGF-I in smooth muscle.

PMID- 12058584
TI  - [Cell transformation and survival mechanisms regulated by GTPase Ral].

PMID- 12058585
TI  - [In vivo apoptotic effect of alpha-2b interferon (IFN) on rat preneoplastic liver
      ].
AB  - In order to know whether IFN alpha prevents in vivo oncogenesis in the very-early
      stage cancer cells, we evaluated the action of IFN alpha-2b on preneoplastic foci
      in rats. Animals were divided into six groups: subjected to an initiation
      promotion model of cancer development (G1), treated with IFN alpha-2b during: a)
      initiation-promotion (G2), b) initiation (G3), promotion (G4); subjected only to
      an initiation stage (G5) and treated with IFN alpha-2b during this period (G6).
      The number and area of rGST P-positive foci were reduced and the Apoptotic index
      was increased in G2, 3 and 6. Bcl-2 and Bcl-XL protein levels were decreased in
      IFN alpha-2b-treated rats. Increased levels of mitochondrial Bax protein were
      observed in G2, 3 and 6. In conclusion, preneoplastic hepatocytes in the IFN
      alpha-2b-treated rats undergo programmed cell death as a result of a significant
      increase of Bax and its translocation to the mitochondria.

PMID- 12058586
TI  - [Human immunodeficiency virus (HIV) co-receptors expression in mononuclear
      leucocytes (ML) of HIV+ patients].
AB  - Variations of the expression of CXCR4 and CCR5 HIV co-receptors after non
      stimulated culture of peripheral blood mononuclear cells (PBMC) from HIV+
      patients were studied. Expression of CCR5 on both CD4+ and CD8+ T lymphocytes was
      reduced after 7 days and remained low throughout the culture. CXCR4 levels
      remained stable in both lymphocyte subpopulations. No significant changes were
      observed in control HIV- PBMC cultures. In order to ascertain if the CCR5 changes
      were associated to in vitro HIV replication, 6 days pre-cultured HIV- PBMC were
      infected with HIV+ culture supernatants. After 3 days CCR5 expression was reduced
      both in CD4+ and in CD8+ T lymphocytes, while CXCR4 expression was not,
      coincident with initiation of HIV replication in culture. These results suggest
      that CCR5 down modulation in CD4+ or CD8+ T lymphocytes is a consequence of HIV
      replication.

PMID- 12058587
TI  - [Functional alterations in central nervous system of prehepatic portal
      hypertensive rats].
AB  - Prehepatic Portal Hypertension (PH) leads to morphologic changes in the rat
      Central Nervous System, including alterations of the blood brain barrier (BBB),
      and astrogliosis and angiogenesis in CA1 and CA4 hyppocampal fields. The present
      study investigates functional changes in portal hypertensive rats. Wistar Kyoto
      rats were used (240 g/bw) and allotted in two groups: GI (n = 8) portal
      hypertensive rats obtained through a regulated stenosis of the portal vein
      (Groszmann), and GII (n = 6), sham-operated rats. We have analyzed: BBB integrity
      with the Trypan Blue diffusion method (TB, Reynolds), protein concentration (PC)
      in Cerebrospinal Fluid (CSF) and plasma (Bradford method),
      electroencephalographic activity (EEG), cerebral edema expressed as brain water
      content (gravidimetric test), and behavior: Animex, righting reflex, pain reflex
      and Rotarod. TB was positive in GI in peripheral vascular areas in hippocampus,
      PC in CSF (ug/ml)(mean +/- SED) was GI: 40.6 +/- 6.8 and GII: 16.5 +/- 4.2 (p <
      0.005), and the plasma levels were (mg/ml): GI: 108.8 +/- 7.6 and GII: 87.4 +/- 2
      (NS). The EEG showed a higher power of the delta band in hypertensive rats (GI:
      0.551 +/- 0.033 and GII: 0.342 +/- 0.031, p < 0.008), but water content was not
      different between GI and GII (water%/per/g/tissue) (GI: 79.21 +/- 0.2, GII: 78.95
      +/- 0.18). These results, showing functional changes in the BBB and brain
      activity without behavioral alterations, suggest the development of a subclinic
      form of hepatic encephalopathy in our model of PH rats.

PMID- 12058588
TI  - [Implantation of transponders at the bottom of the ear in equines].
AB  - In the present work transponders of 2 identification systems have been implanted
      on an exactly defined site at the bottom of the ear on 28 horses. The Backhome
      system is easier to handle and less complicated than the trovan system since it
      is smaller and handier. The hemorrhages that had occurred after the injection
      were mild at 17 animals and moderate at 4 animals. Inflame changes at the
      injection site post application were limited to minor swellings (n = 3) and minor
      pain (n = 6). The interrogator's scope of the two transponder systems is
      different. The interrogator's scope of the trovan transponder was approximate 5
      to 10 cm and of the Backhome transponder approximate 15 to 25 cm resulting in a
      higher benefit. All 14 slaughtered horses were examined pathologically in
      different periods and two transponders were found to have changed their sites
      considerably at approximately 8 to 10 cm compared with the initial injection
      site. The connective tissue surrounding the transponder was transparent and thin
      in cases where the transponder had been implanted 30 days ago or earlier,
      histopathologically the tissue thickness changed. Inflammatory changes appeared
      in 3 cases as a minor perivasculitis and in further 5 cases as a collection of
      single siderophages. In the remaining 5 cases no inflammation was determined. The
      minor changes and lack of inflammation reflect the high biocompatibility of
      transponders.

PMID- 12058589
TI  - [Isoimmune haemolytic icterus in neonatal calves as a consequence of vaccination
      against piroplasmosis].
AB  - The article refers about several cases of isoimmunohaemolytic icterus in neonatal
      calves from different farms, whose dams had all been vaccinated against
      piroplasmosis. Clinical signs of immunomediated icterus neonatorum gravis,
      results of blood chemistry (with special regard to liver-specific parameters in
      the neonatal calf and results of haematology) as well as gross pathology and
      pathohistology are to be discussed. It is summarized, that the most relevant
      indicators for a hepatopathy in the newborn calf are total-bilirubin and the
      glutamate-dehydrogenase. Today, the production of piroplasmosis-vaccines out of
      blood of splenectomized animals is referred to as the only practicable method of
      harvesting sufficient amounts of vaccine-antigen.

PMID- 12058590
TI  - [Bifidobacterium adolescentis suppresses the humoral immune response to an
      autochthonous intestinal bacterium--experiments with gnotobiotic rats].
AB  - On the basis of association-experiments with gnotobiotic rats, we described the
      immunogenicity of two selected bacterial species (Bifidobacterium adolescentis
      and Bacteroides thetaiotaomicron). B. adolescentis is a gram-positive lactic acid
      producing bacterium, strains of which are claimed to have probiotic properties.
      B. thetaiotaomicron is a gram-negative rod, autochthonous to the human as well as
      to the rats' intestinal tract. Colonization of the gut was monitored by
      determination of bacterial cell counts in the animals' feces. In order to
      investigate the systemic immune reaction, the amounts of specific serum-IgG and 
      IgA against both bacterial species were measured in the serum. The intestinal
      immune reaction was examined by measuring the specific IgA in the rats' feces.
      Knowing about the antibody levels in gnotobiotic rats induced by monoassociation
      we subsequently disassociated two groups of rats in order to investigate the
      impact of B. adolescentis on the immune reaction against B. thetaiotaomicron. One
      group was disassociated simultaneously with B. adolescentis and B.
      thetaiotaomicron, the second group was disassociated with these bacteria in
      sequence. B. adolescentis was merely able to induce a mucosal immune reaction,
      while B. thetaiotaomicron challenged the mucosal as well as the systemic immune
      system. Furthermore B. adolescentis obviously suppressed the systemic and mucosal
      immune reaction against the autochthonous B. thetaiotaomicron.

PMID- 12058592
TI  - [Serological studies on prevalence of Toxoplasma gondii in Awassi sheep in
      Syria].
AB  - Survey was conducted in 9 Syrian provinces on clinically healthy Awassi sheep.
      Serum samples were collected from several districts (more than 47 localities--31
      villages and 20 herds). Animals were 1-5 years old. 458 samples were collected in
      spring 1997 and 352 samples were collected from November 1998 through February
      1999. The result indicated that seroprevalence of Toxoplasma gondii ranged
      between 0-100% in the herds and 13.8-74.5% between the provinces. And the mean of
      sero-prevalence was 44.56% in all provinces. The following prevalence were found
      in as indicated: Idleb 74.46%, Hama 72.16%, Deraa 63.35%, Al-Hssakeh 51.11%,
      Suweida 46.98%, Homs 40%, area of Damascus 23.48%, Aleppo 17.02% and Deir Ezzor
      13.79%. The serological titer was 1:4 for 37.67% to 1:64 for 78.93% of the
      positive samples. Results showed that there are 29 (8%) of the positive samples
      with 1:1.000, and only 5 (1.38%) with 1:4.000. It is concluded that the
      Toxoplasma-infections may be one of the main causes of sheep abortions and as the
      source of human infection in Syria. Therefore, it is suggested that further
      epidemical studies are needed.

PMID- 12058591
TI  - Oral immunisation of wild boar against classical swine fever: concluding analysis
      of the recent field trials in Germany.
AB  - The recent oral immunisation trials in wild boar against classical swine fever
      (CSF) in Germany are described and evaluated in summary. After the first field
      study in Lower Saxony from 1993-1995 further immunisation trials started in
      Mecklenburg-Western Pomerania, Brandenburg, Lower Saxony, Baden-Wurttemberg and
      Saxony-Anhalt. The immunisation strategies and the size of the vaccination zones
      were different in the individual federal states. In principle, the bait vaccine
      based on the CSF virus strain "C" were laid out by hand. Later also the aerial
      distribution was carried out in selected areas of Mecklenburg-Western Pomerania.
      The application of baits by plane was introduced at the beginning of the
      immunisation measures in Saxony-Anhalt apart from the manual distribution. Up to
      now, the field trials show that the oral immunisation can be an additional tool
      for CSF control by increasing of herd immunity and reduction of the CSFV
      prevalence. However, the immunisation was not sufficient enough for young boars
      in the most field studies. Based on the evaluation of the immunisation
      experiments an improved immunisation procedure is recommended.

PMID- 12058593
TI  - [The relationship of plasmids from environmental Yersinia isolates and the
      virulence plasmid of enteropathogenic Yersinia strains].
AB  - The human pathogenic strains of Yersinia harbour a conserved plasmid carrying the
      Yop virulon. The virulence plasmid of Yersinia enterocolitica strains belonging
      to the serogroups O:3 and O:9 were used as probes to detect homologous sequences
      in plasmids of "avirulent" Yersinia strains. "Avirulent" Yersinia strains (Y.
      enterocolitica biogroup 1A, Y. intermedia, Y. kristensenii and Y. frederiksenii)
      lack the virulence plasmid. They are widely distributed in the environment and
      can frequently be isolated from clinical samples. Hybridisation experiments
      revealed a number of common genetic elements of the virulence plasmid and the
      plasmids of "avirulent" Yersinia strains. These elements were identified as genes
      involved in plasmid replication, as an endonuclease gene and as mobile genetic
      elements. However, none of the plasmid encoded virulence genes was present in the
      plasmids of "avirulent" Yersinia strains. The frequent occurrence and the
      possible etiological relevance of "avirulent" isolates will be discussed.

PMID- 12058594
TI  - [Investigations of humoral and cellular regulation mechanisms of the redox
      homeostasis in cattle from ecological farming--2. Influence of race and age on
      the enzymatic redox control in the blood plasma].
AB  - The present study examined the effects of race and age on the redox potential
      behavior of blood plasma samples. The blood plasma from clinical healthy heifers
      (44) and calves (45) were investigated. The animals presented three different
      cattle races (Limousin, Angus and Hereford), grazed on pasture. The blood plasma
      test consists of two parts: analysis of the initial redoxpotential as well as the
      investigation of the action of biocatalists. ATP, ATP plus caffeine, GTP and FAD+
      were used as an adding substances for the differential analysis. The influence of
      biocatalist on the redox balance and the reaction of the redox dependent
      enzymatic system of native plasma significant correlated with animal race and
      age.

PMID- 12058595
TI  - [Influence of spiced feed additives on taste of hen's eggs].
AB  - The effect of the spices garlic (Allium sativum), extract from garlic, sage
      (Salvia officinalis), caraway (Carum carvi), peppermint (Mentha piperita), fennel
      (Foeniculum vulgare), thyme (Thymus vulgaris), paprika (Capsicum annuum),
      marjoram (Majorana hortensis), cardamom (Elettaria cardamomum) and sausage-mix
      fed to white hybrides on the quality of eggs (n = 705) was tested by 10 qualified
      persons. Changes in smell or taste were partly significant; a direct improvement
      is hard to induce. A well seasoned taste was obtained by feeding of garlic,
      fennel, peppermint and marjoram. They produce an aromatic flavor. A practical
      application is possible but limited by higher production prices. Further, it is
      uncertain if there is a need for "taste-manipulated" eggs.

PMID- 12058596
TI  - [Parasites of the common crane Grus grus (L.) in Europe].
AB  - 28 species of parasites (8 coccidia, 6 trematodes, 1 cestode, 6 nematodes, 1
      tick, 6 mallophages) were found at the Common Crane. After presenting the
      interconnection of parasites with different carriers as vectors, intermediate and
      several final hosts in the biocoenosis of Common Cranes, the results of
      parasitological examination of 421 samples of cranes resulted in varying
      parasitization at different seasons and flyways. Further studies are needed to
      interprete these facts correctly. Changes of presented localities of diverted
      feedings and their parasitological and bacteriological control at resting places
      may avoid concentration of pathogens in soil, intermediate hosts and carriers.

PMID- 12058597
TI  - [Carl Troester, 1880-83 as veterinarian in Tokyo].
AB  - Carl Troester (1856-1928), royal Prussian junior veterinary surgeon, has been
      sent by command of His Majesty to Tokyo to teach at the Agricultural Faculty
      Japanese students in veterinary medicine. Instruction language is English. The
      course of instruction comprises 36 hours per week. He gains the acknowledgement
      of his pupils and in 1883, on dismissal he has been received by the Tenno. His
      career at the military veterinary academy in Berlin leads to the position of
      veterinary brigadier and professor. With the construction of the sanitary
      institute he has raised himself a memorial.

PMID- 12058598
TI  - [Ultrasonographic examination of the hip joint region and bony pelvis in cattle].
AB  - Transcutaneous and transrectal ultrasonographic examination of the hip joint
      region and the pelvis was carried out in 7 cadavers, transcutaneous
      ultrasonography in 17 healthy young and adult cattle, and transrectal sonography
      was performed in 12 healthy cows in order to study the normal ultrasonographic
      appearance of these regions. 7.5 MHz linear-, 5.0 MHz and 3.5 MHz convex
      transducers and a 7.5 MHz rectal probe were used. The bone surfaces of the
      greater trochanter, the femoral neck and head, the acetabulum and the other
      pelvic bones were visualised as hyperechoic contours. The coxofemoral joint space
      was identified in all cadavers and live cattle. The joint pouch could not be
      visualised, neither in cadavers nor in live cattle. After experimental filling of
      the coxofemoral joint pouch by injection of 35-45 ml eosin-solution it appeared
      as a large anechoic zone between the articular surface and the echogenic joint
      capsule. The inner contours of the pelvic girdle, both iliosacral joint spaces,
      the abdominal aorta and the external iliac arteries were depicted clearly by
      transrectal ultrasonography. The practical application of diagnostic ultrasound
      in these regions is demonstrated in clinical patients suffering from a septic
      coxarthritis and a sequestration of a part of the tuber coxae following an open
      fracture. These results serve as reference data for ultrasonographic
      investigation of disorders of the hip joint and the pelvic region in cattle.

PMID- 12058599
TI  - [Echocardiographic examinations in unsedated racing pigeons (Columbia livia forma
      domestica) with special consideration for the physical training].
AB  - The heart of the bird is characterized by its enormous efficiency. Racing pigeons
      are bred for a long time for their flight performance. In the present study
      therefore the heart of 108 racing pigeons of the breed Bricoux were examined by
      means of echocardiography. The birds were either kept in aviaries (untrained) or
      as racing birds. The aim was to find out whether differences in the heart
      dimensions and/or the heart work occur between untrained and trained birds, like
      it is described already in humans and mammals (so-called athletic's heart).
      Significant differences between the two groups could be determined with different
      parameters, in particular with parameters, which affect the heart work. Thus it
      was for the first time possible to prove the formation of a athletic's heart in
      birds, and by that the adaptation of the avian heart to appropriate performance
      requirements.

PMID- 12058600
TI  - [Effect of reagent batch on activated partial thromboplastin time in canine
      plasma and use of the ratio system for standardization].
AB  - In order to test the variability of the results of the activated partial
      thromboplastin time (APTT) in different reagent batches, 40 samples (20 from
      healthy dogs, 15 from patients with prolonged APTT as a result of different
      congenital or acquired haemostasis disorders, 5 from healthy dogs after in vitro
      addition of heparin) were used to compare 6 different lot Nos. of two commercial
      APTT-reagents (Pathromtin, PTT Reagent). Although the Friedman test showed a
      reagent batch dependency (p < 0.0001) for both reagents, only minor quantitative
      differences were observed with a variation coefficient of 2.7% (Pathromtin) and
      2.4% (PTT Reagent), respectively. A second experiment was based on 105 samples
      measured with two batches of a third reagent (APTT-FS) with remarkable
      differences of results. Convergence of the results was achieved by converting
      into ratio values (quotient measurement value/control). However, statistical
      comparison still showed a significant difference. The study shows the good
      reproducibility of the APTT measured with different batches of the reagents
      Pathromtin and PTT Reagent in canine plasma, indicating that standardization is
      unnecessary. A standardization based on the ratio system can be used for reagents
      with a low batch consistency, requiring a high-quality control.

PMID- 12058601
TI  - [Surgical treatment of patients with spinal infection].
AB  - INTRODUCTION: The surgical treatment of spinal infection, relegated because of
      the development of more effective antibiotherapy and the fear of associated
      morbidity, is springing up again with the increase of new patients with weakening
      pathology. MATERIAL AND METHODS: The clinical records of 27 patients submitted to
      surgery because of spinal infection between January 1990 and December 1999 at our
      service have been retrospectively studied. They were assessed with the Frankel
      and Karnofsky clinical scales, and the radiological angulation of the spine.
      RESULTS: Male (n = 17) and dorsal lesions (n = 14) predominate. Most of patients
      presented with pain, and 13 had neurological compromise. 29 operations were
      performed on the 27 patients. One of them was previously operated upon before the
      period considered, that procedure has been excluded. The total surgeries
      performed were 5 simple and 4 instrumented laminectomies, 6 simple corpectomies,
      10 corpectomies with anterior instrumentation and 4 with posterior
      instrumentation. One patient died, there was not definitive morbidity and any
      patient deteriorated on clinical scales although radiology was not always
      improved. DISCUSSION AND CONCLUSIONS: The aggressive treatment of spinal
      infection is indicated when conservative means are insufficient. Surgery permits
      a better recovery of the neurological deficit, and prevents spinal deformity and
      pain produced by the disease.

PMID- 12058602
TI  - [Idiopathic subarachnoid hemorrhage; comparison of different bleeding patterns
      and long-term outcome].
AB  - INTRODUCTION: Idiopathic subarachnoid haemorrhage (ISAH) represents approximately
      15-30% of all subarachnoid haemorrhages. On the basis of the diagnostic CT and
      depending on the location of the subarachnoid bleeding, patients with ISAH may be
      classified into three groups: a) Patients with normal CT and diagnosis made by
      lumbar puncture (ISAHNCT); b) patients with a pure perimesencephalic pattern
      (ISAHPM) and c) patients with a bleeding pattern resembling that of aneurismatic
      rupture (ISAHA). This classification could permit the establishment of
      differences in the management and prognosis. OBJECTIVES: To describe the clinical
      and radiological characteristics of these three classes of patients and analyse
      their medium and long term outcome and moreover, compare these with those
      observed in patients suffering aneurysmal subarachnoid haemorrhage (ASAH).
      MATERIAL AND METHODS: A series of 122 patients consecutively admitted to Hospital
      12 de Octubre Madrid between 1990 and 2000 with the diagnosis of ISAH were
      retrospectively reviewed. Patients were considered to have suffered ISAH when the
      first complete four vessel angiography did not show the presence of any aneurysm
      or vascular lesion responsible for the bleeding. Patients were classified
      depending on the pattern of bleeding into ISAHNCT, ISAHPM as described by Van
      Gijn et al., and ISAHA. The angiography study was repeated when: a) the first
      study was incomplete or had poor quality, b) vasospasm was present, c) in those
      patients who had an aneurysmal pattern of bleeding in the initial CT. Different
      clinical and radiological characteristics were recorded as well as complications
      that occurred during the hospital stay. Final outcome was evaluated by means of
      the Glasgow Outcome Score (GOS). With the purpose of comparing these clinical and
      radiological characteristics and the outcome of patients with ISAH with those
      suffering aneurysmal subarachnoid haemorrhage (ASAH), 294 patients diagnosed with
      ASAH during the same study period were also reviewed. RESULTS: 27% of patients
      admitted to our hospital with the diagnosis of non-traumatic subarachnoid
      hemorrhaged were diagnosed as ISAH. Of these, 41% presented with a ISAHA pattern,
      39% ISAHPM and 20% ISAHNCT. The average age was similar in the different
      subgroups of SAH, being around 55 years. There was a greater frequency of male
      patients in the ISAHNCT and ISAHPM groups. In comparison with ASAH, ISAH
      characterises by patients presenting with less frequency a bad clinical grade and
      also loss of consciousness at stroke. There are fewer complications in patients
      with ISAH than ASAH, with a frequency of rebleeding and ischemia much less (5 and
      6% respectively). Within the ISAH group, patients with ISAHA pattern of bleeding
      present more complications. Outcome is excellent for patients with ISAHNCT and
      ISAHPM, and rather worse for patients with ISAHA (median followup 5.8 years).
      CONCLUSIONS: This study confirms that the frequency of ISAH in our environment
      reaches the higher limit of that shown previously in the literature, replicating
      the results previously published by our group. Patients with ISAH have a better
      prognosis and a smaller risk of complications than patients with ASAH, the
      prognosis of patients with ISAHCTN and ISAHPM being particularly good. Patients
      with ISAHA present initially with a severe clinical situation, probably related
      to the bigger amount of bleeding, as well as a higher frequency of systemic
      complications, cerebral ischemia and hydrocephalus. However, if the absence of
      vascular lesions is confirmed, the long term prognosis is similar to that of the
      other subgroups of ISAH.

PMID- 12058604
TI  - Medulloblastomas in neurofibromatosis type 1. Case report and literature review.
AB  - A 6-year-old girl, previously diagnosed with neurofibromatosis type 1 (NF-1)
      presented with ataxia and symptoms of raised intracranial pressure. Diagnostic
      work up disclosed a posterior fossa tumor. Histopathological study of the excised
      neoplasm showed a cerebellar medulloblastoma. We review the current literature
      and suggest that the association of medulloblastoma with NF-1 is not a chance
      occurrence, and that it might be pathogenically related. We propose that
      medulloblastoma should be added to the list of malignancies that are apt to occur
      in NF-1.

PMID- 12058603
TI  - [Retropleural paraspinal approach in the treatment of anterolateral thoracic
      spinal diseases].
AB  - The personal experience in the treatment of the spinal and paraspinal thoracic
      pathology using the paraspinal retropleural approach is presented. A total of 18
      patients with neoplastic, traumatic and discal lesions were operated on.
      Improvement of neurological disturbances and pain was noted in all patients. The
      surgical technique for spinal cord and root decompression and also for anterior
      and/or posterior stabilization of the spine is described. The paraspinal
      retropleural approach is compared with the anterior transthoracic approach. The
      advantages of the paraspinal retropleural approach are: low rate of
      complications; allows a very wide decompression of the neurological elements as
      well as an anterior and/or posterior stabilization of the spine by a single
      approach; and it can be easily tailored for each lesion. These advantages are
      enhanced in the management of lesions located in the upper thoracic or
      thoracocervical levels.

PMID- 12058605
TI  - [Cauda equina meningioma in a girl: presentation of a case and review of the
      literature].
AB  - Meningiomas are unusual in childhood, and the intraspinal location is very
      uncommon. Those arising from lumbar dura matter are the most rare among spinal
      neoplasms of meningeal origin. We present the case of a 12-years-old girl with a
      cauda equina meningioma. As in previously reported cases, the initial complain
      was back pain with radicular irradiation. The girl had few neurological findings,
      with pyramidal signs of both lower limbs as single neurological impairment. She
      underwent surgical treatment through an open door laminoplasty and the tumour was
      completely removed without neurological deficit. After 2-year of follow-up she
      remains asymptomatic.

PMID- 12058606
TI  - [Idiopathic granulomatous hypophysitis. Morphological and immunohistochemical
      study of a case].
AB  - Inflammatory diseases of the pituitary gland constitute a group of interest
      because of their scarce frequency, because the disorder presents with symptoms of
      hypopituitarism and expanding sellar mass and because of their therapeutics
      implications. We present one case of idiopathic granulomatous hypophysitis, in a
      55-years-old patient with daily headaches, panhypopituitarism and a sellar mass
      lesion. Granulomatous hypophysitis is characterized by granulomas with
      epithelioid histiocytes and multinucleated giant cells but also shows lymphocyte
      collections. With respect to immunohistochemistry our results show histiocytes
      (CD68+) and an heterogeneous inflammatory infiltrate (CD45RO+ y CD20+). We
      analyze the differential diagnosis with another granulomatous processes,
      infectious or not infectious, and with the histiocytosis. We examine the possible
      relation with the lymphocytic hypophysitis.

PMID- 12058607
TI  - [Deontologic norms for the members of the Luso-Spanish Neurosurgery Society
      edited by the ethics commission presided over by Dr. Maximo Poza, approved at the
      XXXth meeting and applied to the Spanish chapter].

PMID- 12058609
TI  - Web alert. The management of chemical and biological information.

PMID- 12058608
TI  - [First tier measures in the treatment of intracranial hypertension in the patient
      with severe craniocerebral trauma. Proposal and justification of a protocol].
AB  - The management of severe head injuries in general and that of high intracranial
      pressure (ICP) in particular are among the most challenging tasks in
      neurocritical care. One of the difficulties still faced by clinicians is that of
      reducing variability among centers when implementing management protocols. The
      purpose of this paper is to propose a standardized protocol for the management of
      high ICP after severe head injury, consistent with recently published clinical
      practice guidelines and other clinical evidence such as that provided by the
      systematic reviews of the Cochrane Collaboration. Despite significant advances in
      neuromonitoring, deeper insight into the physiopathology of severe brain trauma
      and the many therapeutic options available, standardized protocols are still
      lacking. Recently published guidelines provide sketchy recommendations without
      details on how and when to apply different therapies. Consequently, great
      variability exists in daily clinical practice even though different centers apply
      the same evidence-based recommendations. In this paper we suggest a structured
      protocol in which each step is justified and integrated into an overall strategy
      for the management of severe head injuries. The most recent data from both the
      preliminary and definitive results of randomized clinical trials as well as from
      other sources are discussed. The main goal of this article is to provide
      neurotraumatology intensive care units with a unified protocol that can be easily
      modified as new evidence becomes available. This will reduce variation among
      centers when applying the same therapeutic measures. This goal will facilitate
      comparisons in outcomes among different centers and will also enable the
      implementation of more consistent clinical practice in centers involved in
      multicenter clinical trials.

PMID- 12058610
TI  - Global analysis of large-scale chemical and biological experiments.
AB  - Research in the life sciences is increasingly dominated by high-throughput data
      collection methods that benefit from a global approach to data analysis. Recent
      innovations that facilitate such comprehensive analyses are highlighted. Several
      developments enable the study of the relationships between newly derived
      experimental information, such as biological activity in chemical screens or gene
      expression studies, and prior information, such as physical descriptors for small
      molecules or functional annotation for genes. The way in which global analyses
      can be applied to both chemical screens and transcription profiling experiments
      using a set of common machine learning tools is discussed.

PMID- 12058611
TI  - Component architecture in drug discovery informatics.
AB  - This paper reviews the characteristics of a new model of computing that has been
      spurred on by the Internet, known as Netcentric computing. Developments in this
      model led to distributed component architectures, which, although not new ideas,
      are now realizable with modern tools such as Enterprise Java. The application of
      this approach to scientific computing, particularly in pharmaceutical discovery
      research, is discussed and highlighted by a particular case involving the
      management of biological assay data.

PMID- 12058612
TI  - Structural genomics: bridging functional genomics and structure-based drug
      design.
AB  - Considerable advances in structural genomics have been witnessed in the last
      year. Several pilot studies have begun to report their initial results, and new
      centers have been funded to join the endeavor. The legacies of the genome
      sequencing efforts, namely high-throughput molecular biology and whole-organism
      genome sequences, have been integrated as front-end modules for structural
      genomics pipelines. Impressive advances have been made in NMR spectroscopy and X
      ray crystallography. New methods in structural bioinformatics and computational
      chemistry have been published that provide the means to exploit the wealth of new
      information in drug discovery. Not surprisingly, the biopharmaceutical industry
      has been quick to recognize the benefits of these new developments and has begun
      to adopt them. This article reviews recent results from structural genomics
      initiatives and the potential applications of new information and technologies in
      the drug discovery process.

PMID- 12058613
TI  - Progress in computational methods for the prediction of ADMET properties.
AB  - This review surveys recent progress in the development and application of
      computational techniques for the prediction of absorption, distribution,
      metabolism, elimination and toxicity (ADMET) properties, including intestinal
      permeability, blood-brain barrier penetration, active transport/efflux, aqueous
      solubility, metabolism and toxicity. While much effort continues to be expended
      in this field with some success on existing datasets, perhaps the most pressing
      need at this time is for larger, high-quality sets of experimental data to
      provide a sound basis for model building.

PMID- 12058614
TI  - Fragment analysis in small molecule discovery.
AB  - Cheminformatics is playing an ever-increasing role in small molecule drug
      discovery. The widespread use of high-throughput screening (HTS) and
      combinatorial chemistry techniques has led to the generation of large amounts of
      pharmacological data which, in turn, has catalyzed the development of
      computational methods designed to reduce the time and cost in identifying
      molecules suitable for pharmaceutical development. This review focuses on recent
      advances in the field of substructure analysis, an increasingly popular data
      mining technique with applications at many levels of the discovery process,
      including HTS, compound library design, virtual screening and the prediction of
      biological activity.

PMID- 12058615
TI  - Knowledge-based approaches in the design and selection of compound libraries for
      drug discovery.
AB  - In the past decade, the pharmaceutical industry has realized the increasing
      significance of impacting the early phase hit-to-lead development in the drug
      discovery process. In particular, knowledge-based approaches emerged and evolved
      to address a multitude of issues such as absorption, distribution, metabolism and
      excretion (ADME), potency, toxicity and overall drugability. Each of these
      approaches seeks to bring together all relevant pieces of information and create
      a knowledge-oriented process to deploy such information in drug discovery. This
      review focuses on work relating to drugability, which aims at obtaining hits (or
      leads) that have enhanced likelihoods of leading to successful clinical
      candidates by medicinal chemistry efforts. The period covered in this review is
      from 1997 (since the publication of Lipinski's rule of 5) to March 2002.

PMID- 12058616
TI  - Structure-based approaches to drug design and virtual screening.
AB  - Structure-based design has made an important contribution to drug discovery for
      many years. Recently, the increasing availability of structural data and the
      affordability of high-performance computing platforms have broadened the
      applicability of these methods. In particular, virtual screening has been adopted
      as an effective paradigm for lead discovery that fits in well alongside high
      throughput screening programs. Structure-based virtual screening relies on fast
      and accurate computational methods for the prediction of receptor-ligand binding
      modes and binding affinities. In this paper, recent technical advances in the
      field of molecular docking and de novo design are reviewed, in particular, the
      development of flexible receptor models, docking of combinatorial libraries and
      novel scoring methods.

PMID- 12058617
TI  - High-throughput virtual screening for drug discovery in parallel.
AB  - With the influx of targets generated by genomics and proteomics initiatives, a
      new drug discovery paradigm is emerging. Many companies are setting up target
      family platforms that tackle multiple targets and therapeutic areas
      simultaneously. Virtual screening (VS) techniques are a fundamental component of
      such platforms for in silico filtering of compound collections and prioritization
      of chemistry and screening efforts. At the heart of these, structure-based
      docking and scoring methods are especially effective in identifying bioactive
      molecules if the structure of a target is available. As structural genomics maps
      the structural space of the proteome, these techniques are expected to become
      commonplace. In light of this, an overview of the latest developments in VS
      methodology is given here. In particular, emphasis is placed on those techniques
      adaptable to high-throughput VS in parallel drug discovery platforms. The first
      examples of docking across multiple targets have already appeared in the
      literature and will be reviewed here.

PMID- 12058618
TI  - Initial compound selection for sequential screening.
AB  - Initial leads for drug development often originate from high-throughput screening
      (HTS), where hundreds of thousands of compounds are tested for biological
      activity. As the number of both targets for screening and compounds available for
      screening increase, there is a need to consider methods for making this process
      more efficient. One approach is to screen sequentially, whereby a relatively
      small set of compounds is assayed and the results are statistically analyzed to
      produce a mathematical model. The model is used to predict activity and select
      additional compounds for screening. The new compound bioassay results are added
      to the results for the initial set and a new model is determined. The process
      iterates. The focus of this review is on how to select the initial screening set
      (ISS). It is presumed that the size and quality of the initial set will affect
      the subsequent model building and, hence, the efficiency of finding active
      compounds.

PMID- 12058619
TI  - Multiscale and Bayesian approaches to data analysis in genomics high-throughput
      screening.
AB  - Tremendous amounts of data are produced by high-throughput screening methods
      currently employed in drug discovery and product development. A typical cDNA
      microarray or oligonucleotide-based gene chip experiment easily generates over
      10,000 data points for each array or chip. The challenge of inferring meaningful
      information is formidable given the size and number of these datasets. This paper
      reviews the current status of statistical tools available for gene expression
      analysis, with emphasis on Bayesian approaches and multiscale wavelet filtering.
      Fundamental concepts of Bayesian and multiscale modeling are discussed from the
      perspective of their potential to address important issues related to the
      analysis of gene expression data, such as the fact that genomic data often have
      non-Gaussian distributions and feature localization and multiple scales in both
      frequency and measurement dimension. Recent publications in these areas are
      reviewed. Wavelet filtering and the advantages of multiscale methods are
      demonstrated by application to publicly available gene expression data from the
      National Cancer Institute (NCI). Multiscale methods, including multiscale
      principal component analysis (MSPCA), are applied to extract gene subsets and to
      visualize data in multidimensions for comparisons. Similarity in cell lines and
      gene selection are effectively visualized and quantitatively compared.

PMID- 12058620
TI  - [One hundred years of the Netherlands Association of Surgeons. II. The evolution
      of the Association].
AB  - The Association of Surgeons in the Netherlands was founded 100 years ago with the
      objective to further surgery in general; from 1948 onward a separate objective
      was to further the interests of surgeons. The Association has developed into an
      active scientific society that ensures that quality of Dutch surgical practice,
      that stimulates the development of surgery and that organizes the training of
      surgeons. The number of operations has more than doubled in the past 25 years,
      despite the limited increase in the number of surgeons owing to a great leap in
      efficiency. This has led to a differentiation in the surgical discipline, with a
      number of sub-associations. The currents quality policy emphasizes certification
      of clinics, the development of guidelines, mandatory attendance to ongoing
      training programmes, a registry of complications, adequate patient information,
      visitation of clinics and a compulsory specialization course for all surgical
      residents.

PMID- 12058621
TI  - [A new instrument to measure clinical outcome].

PMID- 12058622
TI  - [The standard "Anemia in first line obstetric practice" from the Royal Dutch
      Organization of Obstetricians (KNOV): risk for not acknowledging iron deficiency
      and hemoglobin abnormalities].

PMID- 12058623
TI  - [The standard "Anemia in first line obstetric practice" from the Royal Dutch
      Organization of Obstetricians (KNOV): risk for not acknowledging iron deficiency
      and hemoglobin abnormalities].

PMID- 12058624
TI  - [A man with a Salmonella dublin infection of the abdominal aortic aneurysm].

PMID- 12058625
TI  - [Diagnostic image (72). An adult women with acromegaly].

PMID- 12058626
TI  - [Hypertensive encephalopathy: does not only occur at high blood pressure].
AB  - A 45-year-old man presented with severe hypertension, headache, cortical
      blindness, and a depressed level of consciousness. A second patient, a 33-year
      old woman, was admitted with pre-eclampsia. She developed lethargy, headache,
      bilateral extensor plantar responses, and seizures. The third patient, a 62-year
      old man, presented with acute renal failure due to necrotising vasculitis and
      glomerulonephritis. Five days after treatment with immunosuppressive drugs had
      been initiated, he developed headache, confusion, seizures, and cortical
      blindness. Hypertensive encephalopathy is characterised by headache, vomiting,
      disturbances in cognition and level of consciousness, visual abnormalities, and
      seizures. Imaging studies often demonstrate oedema of the white matter in the
      posterior parietal and occipital areas of the brain. This so-called reversible
      posterior leucoencephalopathy syndrome is well known in patients with severe
      hypertension, but it is also associated with immunosuppressive drug use and renal
      failure. It can be recognised by its fairly characteristic clinical features
      (different combinations of headache, vomiting, changes in cognition and level of
      consciousness, seizures, muscle weakness, and visual symptoms) and by its
      specific imaging findings. Treatment consists of reducing the blood pressure and
      reducing or discontinuing the use of immunosuppressive drugs. If the treatment is
      started promptly, symptoms and imaging abnormalities are usually reversible.

PMID- 12058627
TI  - [One hundred years of the Netherlands Association of Surgeons. I. Introduction].
AB  - On 9 February 1902, the Association of Surgeons in the Netherlands was founded--a
      remarkable fact. The surgeons, who formerly worked in guilds, were by no means
      the first to found such a society. Some specialist disciplines had already
      preceded them by forming an association. During the course of these 100 years,
      surgery has undergone vast development and progress. This has consequences for
      the deployment of the surgical profession. Subspecialties have arisen, increasing
      the quality of surgical care. Technical possibilities enhance small access
      surgery. This means a very different approach in the training of young surgeons
      in their profession, for instance through the use of virtual reality techniques.

PMID- 12058628
TI  - [Retinopathy in premature infants].
AB  - Retinopathy of prematurity (ROP) is found in about 30% of premature infants with
      a birth weight < 1500 g and/or a gestational age < 32 weeks. Many risk factors
      are directly or indirectly involved in the development of ROP. The younger the
      child and therefore the more immature at birth, the greater the risk of ROP
      leading to short-sightedness or blindness. As a result of advances in obstetric
      and neonatal care, more immature and extremely low birth weight infants survive,
      and thorough ophthalmological screening for ROP is therefore essential. Timely
      detection (ROP stage 3) enables treatment with cryotherapy or laser therapy.
      Although the rate of success has increased with these forms of treatment, about
      40% of the treated children retain a serious visual handicap. In the Netherlands,
      this involves about 10 children each year. At a later age, prematurely born
      children have a higher risk of developing other ophthalmologic problems such as
      strabismus, amblyopia and refractive errors. Again, timely detection and
      treatment reduces the risk of permanent visual disability.

PMID- 12058629
TI  - [The treatment of carpal tunnel syndrome].
AB  - The invasive treatment of carpal tunnel syndrome is only indicated if the
      symptoms persistently interfere with the normal lifestyle (for a period of at
      least several months), and if the diagnosis has been established beyond
      reasonable doubt. The standard treatment still consists of an open surgical
      cleavage of the transverse carpal ligament (with an incision distal to the
      transverse crease of the wrist). Between 75 and 90% of patients obtain long-term
      relief as a result of the operation. Endoscopic release may result in a more
      rapid recovery. However, it is more often associated with complications than the
      conventional operation, and it requires new equipment and extensive training. The
      injection of corticosteroids near the carpal tunnel is reasonably safe and also
      effective, albeit mostly just in the short term; in most patients the symptoms
      recur within a few months.

PMID- 12058630
TI  - [From gene to disease; mutations in the WFS1-gene as the cause of juvenile type I
      diabetes mellitus with optic atrophy (Wolfram syndrome)].
AB  - Wolfram syndrome patients are mainly characterised by juvenile onset diabetes
      mellitus and optic atrophy. A synonym is the acronym DIDMOAD: diabetes insipidus,
      diabetes mellitus, optic atrophy, deafness. Diabetes insipidus and sensorineural
      high-frequency hearing impairment are important additional features. This rare
      autosomal recessively inherited neurodegenerative syndrome is caused by mainly
      inactivating mutations in the WFS1 gene. It is located at chromosome 4p16 and
      encodes wolframin, a transmembrane protein. No function has yet been ascribed to
      this protein.

PMID- 12058631
TI  - [Diagnostic image (90). A women with postprandial abdominal pain and vomiting].

PMID- 12058632
TI  - [Sacral neuromodulation is effective in the treatment of fecal incontinence with
      intact sphincter muscles; a prospective study].
AB  - OBJECTIVE: To evaluate the therapeutic effect of sacral neuromodulation on faecal
      incontinence in patients with structurally intact sphincters. DESIGN:
      Prospective. METHOD: In the period April 1st, 2000 to November 30th, 2001,
      patients with faecal incontinence and structurally intact sphincters were
      included, with or without previous surgery, in whom medicinal treatment and
      biofeedback therapy gave no improvement. Incontinence was defined as involuntary
      loss of stool at least once a week, which was objectified by completion of a 3
      week bowel habit diary. Patients underwent 3 weeks of trial stimulation during
      which they also kept a diary. The trial stimulation was considered successful if
      the diary showed a > or = 50% improvement in continence. RESULTS: 38 patients (31
      women) with an average age of 54 years (range: 26-73) underwent trial
      stimulation. Trail stimulation was carried out using a permanent electrode in 6
      patients and using peripheral neural evaluation in the remaining 32 patients. Two
      patients did not respond to peripheral neural evaluation. Upon assessment after
      the trial stimulation period. continence was found to have improved by > or = 50%
      in 31 (82%) patients. The number of incontinence episodes decreased by an average
      of 86% (range: 50-100). In 27 patients an implantable pulse generator was
      implanted for continuous stimulation. During the average follow-up of 6 months
      the effect remained satisfactory. Anal manometry during stimulation showed no
      increase of sphincter pressures. CONCLUSION: Sacral neuromodulation was of
      therapeutic value in most of the patients treated for faecal incontinence without
      sphincter damage.

PMID- 12058633
TI  - [Persistent renal bleeding treated with selective vascular embolisation with
      preservation of renal function].
AB  - In three patients with persistent blood loss from bleeding or abnormal renal
      vessels, kidney function was preserved by treatment with selective embolisation.
      The first patient, a 42-year-old woman, suffered from persistent haematuria after
      undergoing percutaneous nephrolithotripsy on the left side. Because conservative
      methods had failed and renal artery bleeding as a result of the lithotripsy was
      suspected, angiography with selective coil embolisation of a segmental branch of
      the lower pole artery of the kidney was performed. The second patient, a 40-year
      old man with severe haemophilia A had been suffering from recurring macroscopic
      haematuria for a few months. CT showed an arteriovenous malformation in the right
      kidney. Angiography in combination with embolisation with two detachable balloons
      resulted in occlusion of the malformation. The third patient, a 23-year-old woman
      with tuberous sclerosis, presented with left abdominal pain, haematuria and
      decreasing haemoglobin concentrations. CT revealed a left renal angiomyolipoma,
      10 cm in size, with a large internal haematoma. Three pathological branches of
      the upper pole renal artery were successfully occluded with Gianturco coils. At
      follow-up after 2, 2.5 and 2.5 years respectively, no recurrence of bleeding had
      occurred. Selective embolisation should be attempted as means of treatment for
      persistent renal bleeding if conservative treatment fails. Selective embolisation
      is minimally invasive and has the important advantage of preserving renal
      function.

PMID- 12058634
TI  - [Pulmonary problems associated with lymphoplasmacytic lymphoma (Waldenstrom's
      macroglobulinemia)].
AB  - A 62-year-old man, known for some years due to lymphoplasmacytic lymphoma, was
      admitted with progressive dyspnoea. Multiple lung infiltrates were found upon X
      ray examination. Because of the suspicion of an infection, a bronchoscopy with
      bronchoalveolar lavage was performed. No infectious cause could be established.
      Upon cytological examination, a highly increased level of kappa-positive B
      lymphoid cells was found, as is seen in cases of lymphoplasmacytic lymphoma
      (Waldenstrom's macroglobulinaemia). Following chemotherapy, the dyspnoea lessened
      and the pulmonary infiltrates disappeared. In patients with a lymphoproliferative
      disorder, pulmonary infiltrates due to infection are found relatively frequently.
      This case report highlights a rare complication of the disease, namely pulmonary
      infiltrates caused by infiltration of lymphoplasmacytic cells, emphasising the
      importance of cytological examination of broncho-alveolar lavage fluid.

PMID- 12058635
TI  - Structure and life cycle.

PMID- 12058636
TI  - Merozoite antigens involved in invasion.

PMID- 12058637
TI  - Asexual blood stages of malaria antigens: cytoadherence.

PMID- 12058638
TI  - Rosetting and autoagglutination in Plasmodium falciparum.

PMID- 12058639
TI  - Sexual and sporogonic stage antigens.

PMID- 12058640
TI  - Mouse models of blood-stage malaria infections: immune responses and cytokines
      involved in protection and pathology.

PMID- 12058641
TI  - Malaria and the immune system in humans.

PMID- 12058642
TI  - Genetic regulation of malaria infection in humans.

PMID- 12058643
TI  - Pre-erythrocytic malaria vaccines to prevent Plasmodium falciparum malaria.

PMID- 12058644
TI  - Vaccines against asexual stage malaria parasites.

PMID- 12058645
TI  - Malaria parasites and the anopheles mosquito.

PMID- 12058646
TI  - Transmission-blocking vaccines.

PMID- 12058647
TI  - Nucleic acid vaccines against malaria.

PMID- 12058648
TI  - Antidisease vaccines.

PMID- 12058649
TI  - Adjuvants and malaria vaccine development.

PMID- 12058650
TI  - Malaria vaccine trials.

PMID- 12058651
TI  - Malaria: pathogenicity and disease.

PMID- 12058652
TI  - Sporozoite antigens: biology and immunology of the circumsporozoite protein and
      thrombospondin-related anonymous protein.

PMID- 12058653
TI  - Immune responses to liver-stage parasites: implications for vaccine development.

PMID- 12058654
TI  - Medicaid underfunding crisis threatens patient access.

PMID- 12058655
TI  - PPOM strives for physician satisfaction.

PMID- 12058656
TI  - Talk to your patients about risky behaviors. Diabetes, heart disease and obesity
      are on the rise.

PMID- 12058657
TI  - Group practices listen and learn to improve quality. MSMS resources can help.

PMID- 12058658
TI  - Why--and how doctors leave hospitals for private practice.

PMID- 12058659
TI  - Nuts-and-bolts practice partner program for member physicians.

PMID- 12058660
TI  - Helicobacter pylori eradication for peptic ulceration: an observational study in
      a Scottish primary care setting.
AB  - Despite being established for the treatment of peptic ulcer (PU) disease, few
      studies have assessed the long-term effectiveness and economic benefits of
      Helicobacter pylori (Hp) eradication in primary care. Our aim was to investigate
      the effect of community based Hp eradication for patients with chronic peptic
      ulcer disease requiring maintenance acid suppression. The endpoints used were the
      patients dyspeptic symptoms and the requirement for the prescription of
      maintenance acid suppression therapy. The study area covered seven general
      practices in the Glasgow area. Patients with previously diagnosed peptic ulcer
      disease receiving prescribed acid suppression therapy were invited to a dyspepsia
      clinic. Hp status was assessed by Helisal rapid blood test (HRBT). Positive
      patients received Hp eradication therapy and were reviewed six weeks later. At
      six months a review of practice records was carried out, and two years after
      eradication a postal questionnaire was sent to participating patients. A total of
      243 patients attended the initial clinic of which 81.9% were HRBT positive. 156
      of 196 patients offered Hp eradication re-attended at six weeks. The per protocol
      eradication rate was 91.7%. After six months patients who had received
      eradication therapy were less likely to require maintenance acid suppression
      therapy compared with those to whom eradication was not given. Two years after
      treatment 76.5% of patients felt their symptoms were improved, but 42.2% were
      still receiving maintenance therapy. The estimated cost of treatment per month
      per patient had fallen from 20.23 Pounds to 9.39 Pounds after eradication. In
      conclusion we felt that community based Hp eradication for patients with chronic
      PU disease is effective, however it does not completely alleviate dyspepsia.
      Predictors of symptomatic response or of no longer requiring acid suppression
      therapy after two years were younger age of onset of PU disease and absence of
      pre-documented gastro-oesophageal reflux disease or hiatus hernia. Hp eradication
      improves patients symptoms, reduces the requirement for maintenance acid
      suppression and is cost-effective after two years follow-up in this targeted
      group.

PMID- 12058661
TI  - Is there scope for checking serum biochemistry in the epilepsy clinic?
AB  - We often request blood investigations, almost as a knee-jerk reaction, without
      asking ourselves why and what we expect to exclude or confirm by doing the test.
      We often fail to put the patients presentation into clinical perspective. Here,
      we present a scenario where routine blood tests were unexpectedly abnormal. A
      patient presents to the First Fit clinic, having sustained two generalised tonic
      clonic epileptic seizures. She was commenced on anti-epileptic medication by her
      GP prior to being seen by the neurologists. Routine blood investigations taken in
      the clinic revealed significant hypocalcaemia. She was investigated for the cause
      of this biochemical derangement and started on 1-alphahydroxycholecaliferol. Her
      antiepileptic drug was discontinued once her serum calcium was corrected since
      she was considered to have symptomatic seizures. The discussion deals with the
      causes of hypocalcaemia, which is less commonly encountered than hypercalcaemia,
      and the relevance of checking a patients biochemistry in the First Fit clinic. In
      view of the latter point, there is no clear answer and its use fails to be
      justified by any strong evidence.

PMID- 12058662
TI  - Cadasil: presenting as a mood disorder.
AB  - CADASIL is an autosomal dominant non-atherosclerotic vasculopathy that frequently
      presents as recurrent subcortical strokes, or vascular dementia in middle age.
      Some patients may have prominent mental symptoms or migraine. Widespread white
      matter demyelination and subcortical lacunar infarcts are demonstrated by
      magnetic resonance imaging. Demonstration of granular osmophilic material in
      arteries in skin biopsies is a useful diagnostic tool. CADASIL has been linked to
      mutation in the Notch 3 gene locus on chromosome 19. Genetic testing is available
      for clinical diagnosis.

PMID- 12058663
TI  - An unusual cause of chest pain.
AB  - Pericardial cysts are rare mediastinal cysts, which are commonly asymptomatic. We
      report the case of a middle-aged lady, with a previous short history of chest
      pain, who was found to have a focal pericardial density, felt to have been a
      consequence of haemorrhage into such a cyst.

PMID- 12058664
TI  - George Scharpe, c.1581-1637. A Scots doctor at Montpellier.
AB  - Before the eighteenth century many Scots studied medicine at the medical schools
      of Europe, of which Montpellier was frequently the choice. George Scharpe, an
      early student of the University of Edinburgh, graduated in medicine at
      Montpellier and joined the medical faculty, where his long career can be traced
      from contemporary records. The practice of Scots studying abroad is described, as
      is Languedoc in the early seventeenth century a region and period devastated by
      the religious wars of France.

PMID- 12058665
TI  - A new biomedical magazine: Parasitologia latinoamericana.

PMID- 12058666
TI  - [Cholangiohydatidosis. An evolutive complication of hepatic hydatidosis].
AB  - Hydatidosis is and endemic disease in the south of Chile, especially in Region IX
      where remain rates of high prevalence. Cholangiohydatidosis is an infrequent
      complication of liver hydatidosis. The objective of this paper is to describe
      clinical features of a series of patients with cholangiohydatidosis. Series of
      cases of cholangiohydatidosis treated consecutively and the corresponding follow
      up is reported. Clinical, laboratory and images characteristics are described.
      Descriptive statistic was used its incidence was calculated. In the studied
      period, 13 patients with cholangiohydatidosis were recruited, 9 men (69.2%) and 4
      women (30.7%). Observed laboratory abnormalities were an increment of leukocytes
      in 8 patients (61.5%) and hepatic cholestasis with hepatocyte signs of cytolysis
      in 11 patients (84.6%). Choledocus diameter average measured by ultrasonography
      was 24.7 mm. All the patients had at least one liver cyst whose diameter average
      was of 12.1 cm. At surgery, evidence of biliary communications was detected in
      all patients and biliary decompression was carried out through a choledocostomy
      in 12 patients (92.3%) and by choledocoduodenal anastomoses in one case (7.7%).
      With a mean follow-up of 38.7 months morbility was 23% and mortality 7.7%.
      Accumulated incidence of this entity was of 0.07 cases in 5 years.
      Cholangiohydatidosis is an uncommon complication of liver hydatidosis that
      presents considerable morbidity and mortality rates.

PMID- 12058667
TI  - [Generalized microsporidiosis caused by Encephalitozoon sp. in a pediatric
      patient with Bruton's disease].
AB  - We present the case of a four-year-old boy with a history of repeated upper
      respiratory tract infections and pyoderma. He presented fever, seizures,
      inability to talk, loss of swallowing, fine tremor in the upper extremities;
      positive bilateral Babinski reflex and quadriparesis. The diagnosis of Bruton's
      disease and generalized microporidiosis was based on immunologic analysis, smear
      tests with chromotrope R2 stain and indirect immunofluorescense with monoclonal
      3B6 antibody for Encephalitozoon species in samples of spinal fluid, bronchial
      and paranasal sinus aspirates and stool, which were all positive. The patient was
      treated with albendazol during 72 days; he left the hospital in a good condition,
      walking, talking and able to swallow. His laboratory test controls were negative;
      he is followed up in the outpatient department.

PMID- 12058668
TI  - [New cases of Diphyllobothrium pacificum (Nybelin, 1931) Margolis, 1956 human
      infection in North of Chile, probably related with El Nino phenomenon, 1975
      2000].
AB  - The effect of El Nino/ENSO on terrestrial atmosphere appears to be extremely
      clear. However there are outstanding evidences showing its effect on humans and
      their activities. In fact, prevalence of some parasitic infections have increased
      during El Nino phenomenon. The reasons for that are the migrations of sylvatic
      mammals, fishes and birds as well as by environmental contamination. In this
      report, we show evidence respect of new cases of human infection by
      Diphyllobothrium pacificum clearly associated with a cyclic manifestation of El
      Nino in the Chilean Pacific coast during 1975-2000.

PMID- 12058669
TI  - [Diphyllobothrium pacificum (Nybelin,1931) margolis, 1956 in Canis familiaris
      from Chincha city, Peru].
AB  - In this communication is presented the finding of the tapeworm Diphyllobothrium
      pacificum, parasite of sea lions, in Canis familiaris (dog) in Chincha city,
      Peru. This is the first canine infection with D. pacificum in the South Peruvian
      coast.

PMID- 12058670
TI  - [Parasite fauna and food contents of Notothenia c.f. angustata Hutton, 1875
      (Pisces: Nototheniidae) from two intertidal localities of the Arauco Gulf,
      Chile].
AB  - We studied the parasite fauna and food contents of 38 juvenile of Notothenia c.f.
      angustata specimens captured in the intertidal of Island Santa Maria and Maule,
      in the Arauco Gulf, Chile. Trophic habits of Notothenia c.f. angustata were not
      different between localities, which was mainly algae. A total 11 parasitic taxa
      among were found with the digenean Lecitasther macrocotyle, cestode larvae
      Tetraphyllidea and Diphyllidea and nematode Ascarophis sp. being the dominant
      taxa. The abundance of parasites was similar in the two localities, although the
      infracommunity richness was higher in fish from Maule. The most abundant parasite
      was L. macrocotyle in hosts from Isla Santa Maria, while those from Maule they
      were the Diphyllidea larvae and nematodes Ascarophis sp. The body length of the
      hosts was not a good predictor of the variations in abundance and richness at
      infracommunities, probably because of the early ontogenetic stage of fishes.

PMID- 12058671
TI  - [Search of natural occurrence of xiphidiocercariae (trematoda) in fresh water
      snails of nine countries from Sao Paulo State, Brazil].
AB  - Xiphidiocercariae, aquatic larval stages of some trematodes are considered a
      potential instrument for biological control of mosquitoes. In this study we
      evaluated its natural occurrence in Campinas region and two places in Vale do
      Ribeira (Registro and Miracatu), Sao Paulo State. Snails were obtained from fresh
      water collections from September 1996 to February 1999. The species collected
      were Lymnaea columella, Physa marmorata, Biomphalaria tenagophila, Biomphalaria
      sp., Drepanotrema cimex, D. lucidum and Drepanotrema sp. Fasciola hepatica,
      xiphidiocercariae (Haematoloechidae) and echinostomatid cercariae were detected
      in the lymnaeids snails from Miracatu, SP. In the same locality were found
      planorbids snails parasitized by furcocercariae, echinostomatid cercariae and
      xiphidiocercariae. The xiphidiocercariae found in the planorbids were different
      from those obtained from lymnaeids. One Biomphalaria sp. infected with
      furcocercariae was found in Louveira, SP. In the ROSA place (Campinas, SP) an
      individual of Biomphalaria sp. and one of L. columella were found infected by the
      furcocercariae and echinostomatid cercariae, respectively. In the place UNI-I, in
      Campinas, one L. columella was infected by furcocercariae. Double infection in
      snails from Miracatu was also observed.

PMID- 12058672
TI  - Brachylaima mazzantii (Trematoda): first record in Zenaida auriculata (Aves:
      Columbidae).

PMID- 12058673
TI  - Immunoblot analysis using antigen from Taenia crassiceps cysticerci in the
      diagnosis of swine cysticercosis.

PMID- 12058674
TI  - [A new species of the genus Cameronia Basir (Oxyurida: Thelastomatidae) parasite
      of Gryllodes laptatae Sauss (Orthoptera: Gryllidae) in Argentina].
AB  - Cameronia laplatae n. sp. found in City Bell, Argentina, parasitizing crickets is
      described and illustrated. The new species is distinguished from other members of
      the genus Cameronia by the distribution pattern of the genital papillae in the
      male. It differs from all congeners mainly in having two pairs preanal y two
      pairs postanal papillae.

PMID- 12058675
TI  - Proceedings of the 1st International Symposium Workshop on Circadian Rhythms and
      Clinical Chronobiology. Tokyo, Japan.

PMID- 12058676
TI  - Proceedings of the Periodontal-Systemic Connection: A State of the Science
      Symposium. Bethesda, Maryland, USA. April 18-20, 2001.

PMID- 12058677
TI  - Professional money management for dentists.

PMID- 12058678
TI  - A proper burial.

PMID- 12058679
TI  - A source of happiness.

PMID- 12058680
TI  - Health indicators: building blocks for health situation analysis.

PMID- 12058681
TI  - Case definitions. Meningococcal disease.

PMID- 12058682
TI  - Case definitions. Viral meningitis.

PMID- 12058683
TI  - Epidemiological surveillance system for acute pesticide poisoning.

PMID- 12058684
TI  - Gofer required.

PMID- 12058685
TI  - Positive steps.

PMID- 12058686
TI  - Banking on improvement.

PMID- 12058687
TI  - My day in the OR--frequently asked questions.

PMID- 12058689
TI  - The Decade of the Brain at the C. Mondino Foundation: Ten Years of Research in
      Experimental Neurobiology (1990-2000). Proceedings of a conference. Pavia, Italy,
      June 24-26, 2001.

PMID- 12058690
TI  - Best evidence in anesthetic practice. Prognosis: cognitive function at hospital
      discharge predicts long-term cognitive function after coronary artery bypass
      surgery.

PMID- 12058688
TI  - Current trends in postoperative pain management.

PMID- 12058691
TI  - [The first tissue bank and Dr. Rudolf Klen].

PMID- 12058692
TI  - [Preventive medicine at Hradec Kralove and Dr. Josef Vanicky].

PMID- 12058693
TI  - States feeling the weight of Medicaid shortfalls.

PMID- 12058694
TI  - Antihypertensive drug therapy in Saskatchewan.

PMID- 12058695
TI  - Developments in peer review.

PMID- 12058696
TI  - The hot and the classic.

PMID- 12058697
TI  - Abstracts of the 36th US-Japan Tuberculosis-Leprosy Research Conference. New
      Orleans, Louisiana, USA. 15-17 July 2001.

PMID- 12058698
TI  - Drugs in development.

PMID- 12058700
TI  - Swabs help detect STDs.

PMID- 12058699
TI  - Abacavir hypersensitivity reaction.

PMID- 12058702
TI  - Vaccine trial needs subjects.

PMID- 12058701
TI  - Young using Internet for information.

PMID- 12058703
TI  - Mortality and religion/spirituality: a brief review of the research.

PMID- 12058704
TI  - Cerivastatin and the dissemination of adverse event information.

PMID- 12058705
TI  - Fixed drug eruption with vancomycin.

PMID- 12058706
TI  - Steroid-induced avascular necrosis.

PMID- 12058707
TI  - Rhabdomyolysis from high-dose cerivastatin therapy.

PMID- 12058708
TI  - Octreotide for persistent chylothorax in a pediatric patient.

PMID- 12058709
TI  - Norfloxacin-induced eosinophilia in a cirrhotic patient.

PMID- 12058710
TI  - Dexamethasone pharmacokinetics after high-dose oral therapy for pemphigus.

PMID- 12058711
TI  - Is there a need for critical ethical and philosophical evaluation of hospital
      drugs and therapeutics (D&T) committees?

PMID- 12058712
TI  - [Tissular cestodiasis: role of helper type 1 and 2 t-lymphocytes].
AB  - Cysticercosis and hydatidosis are parasitic diseases caused by larvae of Taenia
      solium and Echinococcus sp., respectively. Parasitic diseases are useful models
      for in vivo studies of effector functions of T helper cell subsets 1 and 2,
      (called Th1 and Th2 on the basis of the pattern of cytokines they produce). The
      polarization to Th1 or Th2 is related to protective or permissive immune
      responses in these diseases. The role of Th1 and Th2 lymphocytes in tissue
      cestodiasis (cysticercosis and hydatidosis) has been studied in experimentally
      infected mice and in human patients; study results suggest that in individuals
      with cysticercosis or hydatidosis, the cellular immune response is polarized to
      Th2, while individuals in whom parasites are killed or their growth is limited,
      have an immune cellular response that is polarized towards Th1. The English
      version of this paper is available at: http://www.insp.mx/salud/index.html.

PMID- 12058713
TI  - Humoral immunity: polycyclic aromatic hydrocarbons and nitrosamines.

PMID- 12058714
TI  - Experimental study of postwintering germination of akinetes and dormant cells of
      cyanoprocaryotes from bottom sediments of blooming and nonblooming ponds.

PMID- 12058716
TI  - The effect of sound intensity on the frequency resolving power of hearing and the
      effect of interference.

PMID- 12058715
TI  - The role of cytokine mRNAs in cell sensitivity to alpha-interferon.

PMID- 12058717
TI  - [Are patients customers? Or where is the health care system propelling us?].

PMID- 12058718
TI  - Renal artery stenosis and ischemic nephropathy.
AB  - Renal artery stenosis (RAS), in its most severe form, can result in diminished
      renal function and loss of kidney mass. The prevalence of ischemic nephropathy is
      greatly under-appreciated in the elderly population and is the source of
      substantial morbidity and mortality. Diagnostic tests for RAS in patients with
      renal insufficiency are problematic, and medical therapy does little to slow the
      natural progression of the disease. Renal artery stenting can achieve long-term
      vessel patency and has been shown to preserve renal function. Proper technique
      and careful case selection are critical to the success of such procedures. Large
      scale trials are needed to clearly identify groups of patients who will benefit
      most from percutaneous revascularization.

PMID- 12058719
TI  - Bibliography. Current world literature. Lipid metabolism.

PMID- 12058721
TI  - Porrorchis nickoli n. sp. (Acanthocephala:: Plagiorhynchidae) from mammals in
      southeastern Mexico, first known occurrence of Porrorchis in the western
      hemisphere.
AB  - Porrorchis nickoli n. sp. is described from the intestine of the gray four-eyed
      opossum Philander opossum (type host), the Virginia opossum Didelphis virginiana,
      the common opossum Didelphis marsupialis, and the white-nosed coati Nasua narica.
      Hosts were collected in southeastern Mexico in the Los Tuxtlas region of the
      state of Veracruz (type locality) and in the states of Tabasco and Chiapas. This
      new species is distinguished from other Porrorchis species by its small proboscis
      (0.286-0.428 mm long x 0.273-0.438 mm wide), a proboscis armature consisting of
      22-24 vertical rows of 7 or 8 hooks per row, and the male reproductive system
      extending postequatorially and occupying only half of the trunk. This is the
      first known occurrence of a Porrorchis species in the Western Hemisphere.

PMID- 12058720
TI  - Subcellular localization of the NAD+-dependent alcohol dehydrogenase in Entamoeba
      histolytica trophozoites.
AB  - The protozoan parasite Entamoeba histolytica is an ancient eukaryotic cell that
      shows morphologically atypical organelles and differs metabolically from higher
      eukaryotic cells. The aim of this study was to determine the subcellular
      localization of ameba NAD+-dependent alcohol dehydrogenase (ADH2). The enzyme
      activity was present in soluble and mainly in particulate material whose density
      was 1.105 in a sucrose gradient. By differential centrifugation, most of the ADH
      activity sedimented at 160,000 g (160,000-g pellet), similar to the Escherichia
      coli polymeric ADHE. In the Coomassie staining of the 160,000-g pellet analyzed
      by electrophoresis, a 96-kDa protein was more prominent than in other fractions;
      this band was recognized by antibodies against Lactococcus lactis ADHE. By gold
      labeling, the antibodies recognized the granular material that mainly constitutes
      the 160,000-g pellet and a material that sedimented along with the internal
      membrane vesicles. By negative staining, the 160,000-g fraction showed helical
      rodlike structures with an average length of 103 nm; almost no membrane vesicles
      were observed in this pellet. In internal membrane fractions, no rodlike
      structures were found, but protomerlike round structures were observed. These
      results indicate that the main amebic NAD+-dependent ADH2 activity is naturally
      organized as rodlike helical particles, similar to bacterial ADHE. Detection of
      ADH2 in membrane fractions might be explained by cosedimentation of the
      multimeric ADH during membrane purification.

PMID- 12058722
TI  - Immunohistochemical detection of interferon-gamma-producing cells in granuloma
      formation of sporotrichosis.
AB  - Granuloma formation is a common response in the skin infection of sporotrichosis.
      The involvement of interferon-gamma (IFN-gamma) and inducible nitric oxide
      synthase (iNOS) in the granuloma formation of sporotrichosis is less known. The
      aim of this study was to describe by immunohistochemistry the exact tissue
      distribution of IFN-gamma-positive cells and iNOS-positive cells in the granuloma
      of skin lesions from patients with sporotrichosis. Formalin-fixed paraffin
      embedded skin biopsy sections from five patients were stained by
      immunohistochemical methods. Mixture of CD4-positive T cells and CD8-positive T
      cells were present in and around the granulomatous lesions. IFN-gamma-positive
      cells, like mononuclear lymphoid cells, were detected in the periphery of the
      granulomas in all samples. The pattern of IFN-gamma staining appeared to be a
      combination of intracellular staining in mononuclear lymphoid cells and
      extracellular deposition in the surrounding tissue. The majority of the
      epitheloid cells and multinucleated giant cells within the granuloma were
      identified by immunostaining for CD68. In contrast, no expression of
      immunoreactive iNOS was observed in those cells in all samples. These findings
      indicate that granulomas of sporotrichosis are coupled with Th1 response.

PMID- 12058723
TI  - Occurrence of Malassezia spp. in the external ear canals of dogs and cats with
      and without otitis externa.
AB  - We studied the lipophilic microbiota of the external ear canals of 332 animals
      (264 dogs and 68 cats), with and without otitis externa, over an 11-year period
      from 1988 to 1999. Malassezia pachydermatis was isolated from 62.2% and 50% of
      dogs with and without otitis externa, respectively, and from 41.2% and 17.6% of
      cats with and without otitis externa, respectively. In the group of animals
      studied for lipid-dependent species, these yeasts were isolated from 4.5% of dogs
      with otitis externa and from 23.1% and 8.9% of cats with and without otitis
      externa, respectively. M. sympodialis and M. furfur were isolated from cats and
      M. furfur and M. obtusa from dogs. Our findings show that lipid-dependent
      Malassezia species may contribute to the etiology of otitis externa in dogs and
      cats.

PMID- 12058724
TI  - Influence of sub-inhibitory concentrations of conventional antifungals on
      metabolism of Candida albicans and on its adherence to polystyrene and
      extracellular matrix proteins.
AB  - Five antifungal agents with different mechanisms of action were compared for
      their ability to affect mitochondrial dehydrogenase activity and adherence
      capacity of Candida albicans to polystyrene and extracellular matrix proteins.
      Only amphotericin B inhibited mitochondrial dehydrogenase activity when the
      culture medium was supplemented with galactose. 5-Fluorocytosine and terbinafine
      did not affect this activity, whereas itraconazole and fluconazole improved it.
      Furthermore, in these experimental conditions, the effect of sub-inhibitory
      concentrations of antifungals on adherence was dependent on the tested antifungal
      and the adherence surface: amphotericin B inhibited adherence to polystyrene and
      fibrinogen, but improved adherence to extracellular matrix. For all surfaces
      tested, when culture medium was supplemented with galactose, fluorocytosine did
      not affect adherence, and itraconazole, fluconazole and terbinafine inhibited
      adherence. Our results also confirmed the influence of the carbohydrates: sub
      minimum inhibitory concentrations (MIC) of itraconazole increased or did not
      modify the mitochondrial metabolism of yeasts when the culture medium was
      supplemented with galactose, but this antifungal always decreased mitochondrial
      metabolism when the culture medium was supplemented with glucose. These data
      indicate that antifungals used below their MIC values can have various effects.
      It is important to distinguish the effects of antifungals on the metabolism of C.
      albicans from effects on its adherence capacity. The former effects are linked to
      the viability of the yeast and the latter depends on the colonization of cellular
      as opposed to inert surfaces.

PMID- 12058725
TI  - CAY-I, a fungicidal saponin from Capsicum sp. fruit.
AB  - Saponins are steroidal or terpenoid-based glycosides with surface active
      properties. A steroidal saponin, CAY-1, with a molecular weight of 1243.35 Da,
      was isolated and purified to homogeneity from commercially available dry, ground
      fruit of Capsicum frutescens. CAY-1 was shown to be a potent fungicide for the
      germinating conidia of Aspergillus flavus, A. fumigatus, A. parasiticus and A.
      niger with species-dependent LD90 values between 3 and 20 microM. Activity
      against some Aspergillus species was affected by the test medium used. In vitro
      assays, CAY-1 was effective against Pneumocystis carinii (IC50): 9.5 microM) and
      Candida albicans (IC90: 6.2 microM). CAY-1 had no effect on the viability of the
      nongerminating conidia of the two filamentous fungi, P. carinii and C. albicans,
      nor on the conidial type of Fusarium oxysporum. It was ineffective against the
      bacteria Enterobacter agglomerans, Bacillus subtilis, Escherichia coli and
      Staphylococcus aureus. CAY-1 was not cytotoxic to A 549 lung carcinoma cells or
      HeLa cells at effective fungicidal concentrations. The results indicate that CAY
      1 is an effective fungicide for Aspergillus species, C. albicans and P. carinii
      at concentrations below the threshold for mammalian cell toxicity.

PMID- 12058726
TI  - Effects of erythromycin, clarithromycin, roxithromycin and azithromycin on murine
      gut colonization by Candida albicans.
AB  - Male Crl:CD1(ICR) BR mice were fed either chow containing Candida albicans or
      regular chow. The gastrointestinal tract of the C. albicans-fed mice was
      permanently colonized by the yeast. Groups of C. albicans-colonized mice were
      subsequently treated either with a macrolide (erythromycin, clarithromycin,
      roxithromycin or azithromycin) for 10 days or a normal saline solution
      (controls). Other controls included non-colonized mice receiving the same
      antibiotics or a saline solution. Our data are as follows: (i) C. albicans
      colonized mice treated with each macrolide had highly significant increase in
      colony counts of C. albicans in their stools compared to C. albicans-colonized
      mice treated with saline only; (ii) discontinuation of macrolide treatment showed
      a trend towards lower colony counts, which was not statistically significant
      (colony counts were sustained even after discontinuation of antibiotic
      treatment); (iii) dissemination of C. albicans did not occur; (iv) mice fed
      regular chow treated with the study drugs or saline did not have any yeasts in
      their stools. In conclusion, oral erythromycin, clarithromycin, roxithromycin and
      azithromycin cause a modest increase of the C. albicans concentration of the
      gastrointestinal tract. This increase is not associated with a higher risk of
      disseminated candidiasis.

PMID- 12058727
TI  - Chrysosporium anamorph of Nannizziopsis vriesii associated with fatal cutaneous
      mycoses in the salt-water crocodile (Crocodylus porosus).
AB  - The Chrysosporium anamorph of Nannizziopsis vriesii, recently identified as the
      cause of cutaneous infections in chameleons and brown tree snakes, was associated
      with skin infections and deaths in salt-water crocodile (Crocodylus porosus)
      hatchlings on two separate occasions 3 years apart. In all, 48 animals died from
      the infection. All hatchlings came from the same farm in northern Queensland,
      Australia.

PMID- 12058728
TI  - Enhanced production of specific IgG4, IgE, IgA and TGF-beta in sera from patients
      with the juvenile form of paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM) occurs in two distinct forms, the acute or juvenile
      form (JF), and the chronic or adult form (AF). To clarify the basis of this
      dichotomy, specific IgG subclasses, IgA and IgE anti-gp43 were measured by enzyme
      linked immunosorbent assay, in patients with different forms of PCM. Serum levels
      of tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, macrophage inflammatory
      protein (MIP)-1alpha and transforming growth factor (TGF)-beta were also
      quantified. We show here that JF patients have significantly higher titers of IgE
      antibodies against gp43, an immunodominant antigen specific for Paracoccidioides
      brasiliensis, than do patients with the unifocal adult form (UF-AF, isolated
      lesions). Patients with the multifocal adult form (MF-AF, lesions in more than
      one organ) also produced elevated levels of anti-P. brasiliensis IgE.
      Furthermore, specific IgE levels were correlated with IgG4, IgA and eosinophilia.
      Patients with JF showed eosinophilia and increased levels of TGF-beta, a
      switching factor for IgA. These results indicate a T helper (Th)-2 pattern of
      cytokine expression in both the JF and the MF-AF of PCM. On the other hand,
      patients with UF-AF had a significantly lower production of specific IgE, IgG4
      and IgA than was seen in the other patient groups.

PMID- 12058729
TI  - Correlation of the frequency of petite formation by isolates of Saccharomyces
      cerevisiae with virulence.
AB  - In previous studies on the colony phenotype switching of Saccharomyces
      cerevisiae, we observed that the least virulent isolates formed greater numbers
      of petite colonies when grown at body temperature, 37 degrees C. To determine if
      there is a link between virulence and petite formation, we examined the frequency
      of spontaneous petite formation for virulent clinical isolates (YJM128, YJM309),
      an intermediate virulent segregant of YJM128 (YJM145) and avirulent clinical
      (YJM308) and nonclinical S. cerevisiae (Y55, YJM237) after growth at 37 degrees
      C. The rank order of increasing frequency of petite formation was YJM128 = YJM145
      < YJM309 < Y 55 < YJM308 = YJM237, which is similar to the rank-order of
      virulence in CD-1 mice. To assess the virulence of petites in vivo, two mouse
      models, CD-1 and DBA/ 2N, were infected i.v. with 10(7) cfu of either the
      parental grand or a spontaneously derived petite from one of four isolates
      previously classified with differing degrees of virulence: YJM128, YJM309, YJM145
      and Y55. In both CD-1 and DBA/2N, the mean log10 cfu of grands recovered from the
      brain was significantly higher than that of the petites (P<0001). Overall,
      petites were significantly less virulent than the parental strains. However,
      death of some DBA/2N mice caused by YJM128 petite 1 showed that petites are not
      totally avirulent. To see if S. cerevisiae isolates form petite colonies in vivo,
      both mouse models were infected with parental grands of YJM128 and Y55. Recovered
      colonies were counted and confirmed as grand or petite, and the frequency of
      petite colonies in the brain, the target organ, correlated with the in vitro
      results. Overall, these studies show an inverse correlation between the frequency
      of petite-colony formation and the previously determined virulence of S.
      cerevisiae in CD-1 mice. Furthermore, petites were significantly less virulent
      than the parental grands, in most cases, and petites are spontaneously formed in
      vivo at a frequency inversely correlated to the virulence of the strain.

PMID- 12058730
TI  - Experimental paracoccidioides brasiliensis infection in mice: influence of the
      hormonal status of the host on tissue responses.
AB  - We have previously proposed that 17beta-estradiol may be responsible in part for
      the decreased frequency of clinical paracoccidioidomycosis in females via a
      blocking of the initial morphological transformation necessary to initiate
      infection. Here we examined the course of infection in male and female mice in
      relation to their hormonal status. After pulmonary infection with conidia, normal
      males showed progressive infection, whereas normal females restricted
      proliferation and progressive disease. In contrast, castrated animals exhibited
      lesser capacity to restrict disease progression. Castrated male mice
      reconstituted with 17beta-estradiol initially restricted proliferation, but
      showed disease progression later in infection, whereas castrated female mice
      reconstituted with testosterone were unable to restrict disease. Quantitative
      histological analyses demonstrated that only normal male and castrated
      reconstituted mice developed granulomas, which decreased in number and size with
      time correlating with increasing numbers of CFU in the lungs. Greater numbers of
      chronic inflammatory foci did not correlate with higher CFU. These results
      further support a role for 17beta-estradiol during early innate resistance of
      females to paracoccidioidomycosis.

PMID- 12058731
TI  - In vitro susceptibility of Microsporum canis and other dermatophyte isolates from
      veterinary infections during therapy with terbinafine or griseofulvin.
AB  - We investigated the in vitro activity of terbinafine against fresh veterinary
      isolates of Microsporum canis and the potential of this organism to develop
      resistance in vivo during oral therapy. Dermatophyte cultures (n = 300) were
      obtained from naturally infected cats and dogs undergoing oral therapy with
      terbinafine or griseofulvin. M. canis comprised 92% of isolates; other species
      included Microsporum gypseum and Trichophyton mentagrophytes. Minimum inhibitory
      concentrations (MICs) and minimum fungicidal concentrations (MFCs) of terbinafine
      and griseofulvin were determined by broth macrodilution assay. Terbinafine was
      highly active against all three species with MIC90< or =0.03 microg ml(-1), in
      agreement with published data. However, terbinafine exhibited primary cidal
      activity against 66% of Microsporum isolates (n = 275) in contrast to the almost
      complete cidal effect in Trichophyton (n = 18). Griseofulvin was significantly
      less active than terbinafine (MIC90 = 4 microg ml(-1)) but had a primary cidal
      action on about 40% of the isolates. The data were analysed for changes in MIC
      and MFC during the course of therapy, which could be indicative for development
      of acquired resistance. Oral treatment of 37 animals with terbinafine for up to
      39 weeks caused no increase in MIC or MFC of terbinafine, either in individual
      patients or in the whole group.

PMID- 12058732
TI  - Characterization of a protein kinase C gene in Sporothrix schenckii and its
      expression during the yeast-to-mycelium transition.
AB  - The yeast-to-mycelium transition in Sporothrix schenckii has been shown to
      respond to protein kinase C (PKC) effectors, indicating the involvement of PKC in
      this regulation. In this study, we identified the presence of two pkcl-like genes
      in S. schenckii. Using fungal genomic DNA as template and primers targeted to
      conserved sequences in the Saccharomyces cerevisiae pkc1 gene, two partially
      overlapping extra long polymerase chain reaction (XL-PCR) products were obtained.
      These XL-PCR products were sequenced and found to encode part of the C3/C4
      domains of two different PKC-like proteins. The presence of two different genes
      was confirmed by Southern blot analysis. These two genes were named pkcSs-1 and
      pkcSs-2. The sequence of the pkcSs-2 gene was completed and revealed an open
      reading frame of 3942 nucleotides interrupted by five introns. A transcript of
      8.7 kb was detected in northern blot analysis of poly A+ RNA. The pkcSs-2 gene
      encodes a protein of 1194 amino acids and 132.84 kDa that contains the
      characteristic structure and domains of other fungal PKCs reported to date. Using
      reverse transcription-PCR (RT-PCR), the pkcSs-2 gene was found to be expressed at
      all intervals tested during the yeast-to-mycelium transition.

PMID- 12058733
TI  - Fungicidal activities of commonly used disinfectants and antifungal
      pharmaceutical spray preparations against clinical strains of Aspergillus and
      Candida species.
AB  - The antifungal efficacy of commercial chemical disinfectants and pharmaceutical
      antifungal agents against medically important moulds and yeast species was
      investigated. Chlorine, phenol, sodium dodecyl sulfate and quaternary ammonium
      salts were the chemical disinfectants, and bifonazole and terbinafine were the
      antifungal pharmaceutical products tested against clinical isolates of
      Aspergillus and Candida species. Fungal inocula were obtained from conidial
      preparations of two A. ochraceus strains and yeast cells of C. albicans, C.
      krusei and C. parapsilosis. The antifungal activities were evaluated either by
      determining the kill rate in a cell suspension media at different contact
      periods, or by examining the viability and growth on plates sprayed with the
      active ingredient. Chlorine (1%) was the only disinfectant with the ability to
      cause a rapid inactivation of all five strains. Phenol (5%) was equally effective
      against Candida species; however, a number of A. ochraceus conidia were able to
      survive this treatment for up to 1 h. Benzalkonium chloride (0.5%) and cetrimide
      (0.5%) were also able to disinfect the three Candida species rapidly; however,
      these two quaternary ammonium compounds were relatively ineffective against A.
      ochraceus. In spray experiments, quaternary ammonium compounds had a fungicidal
      activity against Candida species and were fungistatic against A. ochraceus
      conidia. All five fungal strains were able to resist 0.5% sodium dodecyl sulfate,
      present either in the suspension solution or on the sprayed plate. Of the two
      pharmaceutical antifungal products tested, bifonazole (1%) were essentially
      ineffective against all five strains. Terbinafine (1%) had a fungicidal activity
      against A. ochraceus and C. parapsilosis. In suspension experiments, an exposure
      to 0.01% terbinafine required a contact period of 1 h for a complete inactivation
      of A. ochraceus conidia and an onset of fungicidal effect on C. parapsilosis
      yeast cells. Terbinafine was only moderately effective against C. albicans and
      was completely ineffective against C. krusei.

PMID- 12058734
TI  - Onychomycosis due to Onychocola canadensis: report of the first two Spanish
      cases.
AB  - Onychocola canadensis is a non-dermatophytic mould that may cause distal and
      lateral subungual or white superficial onychomycosis. It was first reported in
      1990. To date, it has been reported only from temperate countries, namely Canada
      (14 cases), New Zealand (3), France (9) and the United Kingdom (4). We report the
      first two cases from Spain.

PMID- 12058735
TI  - A case of imported paracoccidioidomycosis in a German legionnaire.
AB  - We report on a case of the chronic form of paracoccidioidomycosis with swelling
      and ulcerations of the mouth in a German legionnaire who also suffered from a
      chronic bronchitis. The patient had worked for many years in Brazil, an area
      endemic for the disease. Infection due to Paracoccidioides brasiliensis was
      diagnosed in Germany, more than 10 years after the patient's return. Diagnosis
      was established by the presence of yeast cells with multipolar budding in the
      tissue of the oral lesion. Furthermore, the fungus was grown in a liquid
      Leishmania culture medium. Identification of the fungus was based on morphology
      and genetic sequencing. Furthermore, IgG antibodies against a 43-kDa antigen of
      P. brasiliensis were detected in a western blot. After itraconazole therapy (400
      mg day(-1)) for 4 weeks, the lesions had disappeared almost completely, but the
      therapy was continued for further 5 months to avoid relapse of the infection.

PMID- 12058736
TI  - A pulmonary infection caused by Coprinus cinereus (Hormographiella aspergillata)
      diagnosed after a neutropenic episode.
AB  - In a patient treated for a non-Hodgkin's lymphoma, a lung abscess caused by
      Hormographiella aspergillata (stat. anamorph. Coprinus cinereus) was diagnosed
      using an ultrasound-guided puncture of the lesion. The patient appeared to
      respond to amphotericin B, but at the same time was also recovering from her
      neutropenic episode. The extent to which each of these two factors explains the
      complete resolution of the infection is unclear. Expert classical morphological
      examination and molecular typing methods were needed to identify this filamentous
      basidiomycetous fungus.

PMID- 12058737
TI  - Cryptococcus neoformans var. gattii meningitis in Singapore.
AB  - We describe here two cases of Cryptococcus neoformans var. gattii meningitis that
      occurred in Singapore. This variety of Cryptococcus neoformans differs from the
      more widely known C. n. var. neoformans in its ecology and epidemiology.
      Infections with this variety are still rare in Singapore.

PMID- 12058738
TI  - Height responses in complete idiopathic growth hormone deficient children less
      than three years of age during growth hormone therapy. Executive Committee of the
      International Cooperative Growth Study in Japan.
AB  - To know the effect of the age factor on growth response to growth hormone (GH)
      therapy in patients less than three years of age with complete idiopathic growth
      hormone deficiency (GHD). One hundred thirty-seven prepubertal children with
      complete idiopathic GHD from the database of the International Growth Cooperative
      Study (ICGS) of Japan for more than two years were analyzed. The patients were
      divided into four groups according to age at the start of GH therapy; group 1, <
      or = three years, group 2, three to < or = six years, group 3, six to < or = nine
      years, group 4, >nine years. In group 1 the mean birth weight SDS of -0.17 was
      not the lowest. Patients in group 1 had the lowest HSDS (-4.53) at the start of
      the therapy (P<0.01). During two years of the treatment, the mean HSDS improved
      from -4.53 to -2.15 with an increase in mean SD score of 2.12 in group 1, but in
      group 4 it was only 0.92 (P<0.01). In group 1, the mean HSDS declined from -0.17
      at birth to -4.53 progressively. Delta height SDS during the first year of
      treatment in Group 1 was 1.59 SD, which is the highest. The decrease in
      %overweight during the first year showed that in group 1, the reduction in
      adiposity was the greatest among the groups (P<0.05). Our data showed that in
      children with complete GHD less than three years of age, there was severe growth
      failure, and the onset was not in the prenatal period, but in the postnatal
      period. Early detection of GHD and therapy with GH is important because
      normalization of height may be achieved earlier than in older age groups.

PMID- 12058739
TI  - Molecular mechanisms of chromosome pairing, folding and function.

PMID- 12058740
TI  - Stereoscopic vision in the cat.

PMID- 12058741
TI  - Relation between prostaglandin E2 and adrenaline reversal in the rat uterus.

PMID- 12058742
TI  - Acute effect of oral and subcutaneous administration of monosodium glutamate on
      the arcuate nucleus of the hypothalamus in mice and rats.

PMID- 12058743
TI  - Sensitivity of fish ATPases to polychlorinated biphenyls.

PMID- 12058745
TI  - Brain catecholamines and human sleep.

PMID- 12058744
TI  - Effect of pregnancy on the isoantibody response in rabbits.

PMID- 12058746
TI  - Induction of mesodermal and endodermal structures and primordial germ cells in
      Triturus ectoderm by a vegetalizing factor from chick embryos.

PMID- 12058747
TI  - Murine leukaemia virus group-specific antigen in the C-type virus-containing
      human cell line, ESP-1.

PMID- 12058748
TI  - Virus-like agents from patients with Hodgkin's disease.

PMID- 12058749
TI  - Toxicity of the photoisomers of cyclodiene insecticides to freshwater animals.

PMID- 12058750
TI  - Drug dependence and phenotypic masking in E. coli.

PMID- 12058751
TI  - Cell division after laser microirradiation of mitotic chromosomes.

PMID- 12058752
TI  - Single-gene heterosis in Drosophila revealed by inbreeding.

PMID- 12058753
TI  - Survival of mouse embryos after freezing and thawing.

PMID- 12058754
TI  - Unsuccessful attempts to transfer morphine tolerance and passive avoidance by
      brain extracts.

PMID- 12058755
TI  - Formation of cerebrospinal fluid in spinal subarachnoid space.

PMID- 12058756
TI  - Immunological suppression of the occurrence of spontaneous mammary tumours in
      C3H/He mice.

PMID- 12058757
TI  - Chromosome polymorphism in American Negro and White populations.

PMID- 12058758
TI  - Role for ferredoxins in the origin of life and biological evolution.

PMID- 12058759
TI  - Structure of alpha-keratin.

PMID- 12058760
TI  - Geometry of the myosin dimer.

PMID- 12058761
TI  - Extended sleep and performance.

PMID- 12058762
TI  - Mechanisms of sound localization.

PMID- 12058764
TI  - Bioethics and public policy in the next millennium: presidential address.

PMID- 12058763
TI  - Evolution of head development.

PMID- 12058765
TI  - Divisibility and the moral status of embryos.
AB  - The phenomenon of twinning in early fetal development has become a popular source
      for doubt regarding the ascription of moral status to early embryos. In this
      paper, the possible moral basis for such a line of reasoning is critically
      analysed with sceptical results. Three different versions of the argument from
      twinning are considered, all of which are found to rest on confusions between the
      actual division of embryos involved in twinning and the property of early embryos
      to be divisible, to be based on highly questionable ethical assumptions, or to
      imply inconsistent claims regarding the moral importance of potentiality and/or
      the moral status of embryos. This is taken to expose a number of related
      inconsistencies in the moral basis of pro-life positions. In particular,
      ascribing moral significance to the property of being (in)divisible is found to
      be incompatible with the claim that human individuals possess unique values which
      could underpin an absolute moral ban on murder.

PMID- 12058766
TI  - Informed consent procedures: responsibilities of researchers in developing
      countries.
AB  - We describe the informed consent procedures in a research clinic in Santiago,
      Chile, and a qualitative study that evaluated these procedures. The recruitment
      process involves information, counseling and screening of volunteers, and three
      or four visits to the clinic. The study explored the decision-making process of
      women participating in contraceptive trials through 36 interviews. Women
      understood the research as experimentation or progress. The decision to
      participate was facilitated by the information provided; time to consider it and
      to discuss it with partners or relatives; and perceived benefits such as quality
      of care, non-cost provision of methods and medical care. For some women,
      participation was an opportunity to express altruism. The main obstacles for
      participation were perceived side effects or risks. The final risk-benefit
      balance was strongly influenced by women's needs. Women perceived that the
      consent form benefited the clinic, proving that participants had made a free
      decision, and benefited the volunteers by warranting their right to free medical
      care. The most important problem detected was occasional misunderstanding of the
      information given on the form. We concluded that a full decision-making process
      enhances women's ability to exercise their right to choose, and assures research
      institutions that trials are conducted without coercion and that the participants
      are committed to the study. Researchers have the responsibility of conducting
      this process.

PMID- 12058767
TI  - Procreative beneficence: why we should select the best children.
AB  - Eugenic selection of embryos is now possible by employing in vitro fertilization
      (IVF) and preimplantation genetic diagnosis (PGD). While PGD is currently being
      employed for the purposes of detecting chromosomal abnormalities or inherited
      genetic abnormalities, it could in principle be used to test any genetic trait
      such as hair colour or eye colour. Genetic research is rapidly progressing into
      the genetic basis of complex traits like intelligence and a gene has been
      identified for criminal behaviour in one family. Once the decision to have IVF is
      made, PGD has few 'costs' to couples, and people would be more inclined to use it
      to select less serious medical traits, such as a lower risk of developing
      Alzheimer Disease, or even for non-medical traits. PGD has already been used to
      select embryos of a desired gender in the absence of any history of sex-linked
      genetic disease. I will argue that: (1) some non-disease genes affect the
      likelihood of us leading the best life; (2) we have a reason to use information
      which is available about such genes in our reproductive decision-making; (3)
      couples should select embryos or fetuses which are most likely to have the best
      life, based on available genetic information, including information about non
      disease genes. I will also argue that we should allow selection for non-disease
      genes even if this maintains or increases social inequality. I will focus on
      genes for intelligence and sex selection. I will defend a principle which I call
      Procreative Beneficence: couples (or single reproducers) should select the child,
      of the possible children they could have, who is expected to have the best life,
      or at least as good a life as the others, based on the relevant, available
      information.

PMID- 12058768
TI  - Ethical and legal issues in xenotransplantation.
AB  - In most western countries, there is a 'human organ shortage' with waiting lists
      for the performance of transplantation. In a recent report of the UNOS Ethics
      Committee it is stated that there are approximately 31,000 potential recipients
      on waiting lists, but only one fourth of potential donors give their specific
      consent. Xenotransplantation--defined as the transplantation of animal cells,
      tissues or organs into human beings--is associated with particular ethical
      dilemmas, namely the problems of efficiency and safety of this medical procedure.
      The objective of this study is to analyse the ethical dilemmas in
      xenotransplantation with the background of a personal view of moral life. Also,
      xenotransplantation will be evaluated as far as the legal regulation of
      transplantation is concerned. In particular, we will consider patients rights in
      accordance with existing laws on organ and tissue transplantation, animal
      research and clinical trials.

PMID- 12058770
TI  - A critical approach to the current understanding of Islamic scholars on using
      cadaver organs without prior permission.
AB  - Chronic organ diseases and the increasing demand for organ transplantation have
      become an important health care problem within the last few decades. Campaigns
      and regulations to encourage people to donate organs after death have not met
      with much success. This article discusses the subject from an Islamic
      perspective. It beings with some basic information on how Muslims reach legal
      rulings on a particular issue, and goes on to debate contemporary thinking among
      Islamic scholars on the ethical-legal issues of organ donation and organ
      transplantation. It is shown that there are two groups of scholars, one allowing
      organ donation and organ transplantation, the other refusing it in any
      circumstances. Both groups agree that is is fundamentally wrong to harvest organs
      from cadavers without prior permission of the deceased or the relatives. This
      dogma is re-examined, and it is argued that, under the rule of necessity and the
      imperative to preserve life, there is enough moral and theological ground to
      allow the state to harvest organs from the deceased without prior permission.

PMID- 12058769
TI  - A critical analysis of Australian clinical ethics committees and the functions
      they serve.
AB  - The predominant function of Australian clinical ethics committees (CECs) is
      policy formation. Some committees have an educational role. Few committees play
      any direct role in advising on ethics in the management of individual patients
      and this occurs only in exceptional circumstances. There is a tendency to
      exaggerate both the number and function of committees. It is suggested that
      studies of ethics committees, based on questionnaire surveys, should be
      interpreted cautiously. An examination of ethical issues indicates that there is
      a role for a critical analysis of power relations in Australian hospitals that is
      not fulfilled by CECs.

PMID- 12058771
TI  - Beneath the rhetoric: the role of rights in the practice of non-anonymous gamete
      donation.
AB  - The use of rights based arguments to justify claims that donor offspring should
      have access to information identifying their gamete donor has become increasingly
      widespread. In this paper, I do not intend to revisit the debate about the
      validity of such rights. Rather, the purpose is to examine the way such alleged
      rights have been implemented by those legislatures that have allowed access to
      identifying information. I will argue that serious inconsistencies exist between
      the claim that donor offspring have a right to know the identity of their gamete
      donor and the way such a right is currently met in practice. I hope to show that
      in systems where non-anonymous donation is practised, an understanding of the
      proclaimed right of donor offspring to know their genetic identity is one
      composed of two different rights--the right to know the circumstances of their
      conception and the right to information identifying the gamete donor--can provide
      important insights into this important area of public policy.

PMID- 12058772
TI  - Constitution and common law in bioethics.
AB  - In recent years legal intervention in bioethical matters has increased notably
      following various paths: court decisions, parliamentary acts, codes of conduct
      and solemn declarations (i.e. European Bioethics Convention, 1997, or the UNESCO
      Genome Declaration, 1997). Body and liberty, as a question of fundamental legal
      rights, are constitutionalized along two paths. The former is vertical (a text
      created at central level is open to ratification and domestic implementation to
      finally become the rule in concrete cases). The latter is, above all, horizontal.
      It is characterized by the existence at world level of a number of centres and
      institutions, with the judiciary and judge-made law playing a major role. The
      most important new rights and freedoms in bioethics have been recognized in this
      ever-changing and troubled environment. The horizontal way has the great
      advantage of considering the differences as a resource and not as a limit. In the
      case law on bioethics a sort of jurisprudential model seems to be at work, that
      goes some way toward a judge-made law at a universal level. Cases such as Cruzan,
      Bland and Massimo held the fundamental concept of self-determination with
      surprising similarity. But we don't know if one of them has influenced the
      others, always supposing that the judges were aware of them. Today's first duty
      is to raise the consciousness of judges as to how common their problems are and
      how often their rulings are similar to each other's.

PMID- 12058773
TI  - Points to consider for ethics committees in human gene therapy trials.
AB  - Recent political developments and disclosures of serious adverse events in human
      gene therapy (HGT) with the death of 18-year old Jesse Gelsinger in the USA have
      shown that the clinical application of HGT raises some severe ethical issues.
      These have either been neglected or not yet been discussed to a satisfactory
      extent. In this paper, we will address this deficiency and develop strategies for
      a safer application of HGT. Such a study must first look closely at the science
      of HGT itself. We will evaluate the latest preclinical research, especially data
      on the viruses that are used as vectors and on modes of administration of
      vectors. We will put forward new arguments concerning the toxicity assessment of
      so-called 'gene drugs', the tissue and cell type specificity of the vectors, and
      the duration and on-set of gene expression. Secondly, we will look at procedural
      aspects of applied research ethics on the way to clinical application of HGT.
      There, informed consent (IC) and the patient-researcher relationship are of
      utmost concern. Furthermore, we will explore the problem of expertise in risk
      assessment and will show how current regulations foster conflicts on interests
      that create dilemma situations even for those researchers who act in the best
      interest of the patients. We will conclude the article with a set of questions
      for ethicists who have to decide about the quality of HGT protocols. This may
      contribute to the safety of patients participating in HGT trials and to achieving
      the aim of efficient application of HGT.

PMID- 12058774
TI  - U.S. medical research in the developing world: ignoring Nuremberg.

PMID- 12058775
TI  - Who defers to whom? The Attorney General targets Oregon's Death with Dignity Act.

PMID- 12058776
TI  - The "art" of procreation: why assisted reproduction technology allows for the
      preservation of female prisoners' right to procreate.

PMID- 12058777
TI  - The benefit of negative tests in non-ulcer dyspepsia.
AB  - OBJECTIVES: Negative diagnostic tests are usually evaluated by their ability to
      advance a diagnostic search, or they are considered redundant expenditures in
      establishing a definitive diagnosis. It has remained difficult to assess their
      benefit in terms of their own merit and the reassurance that they provide to a
      patient. The aim of the present study is to develop a mathematical model for
      quantifying the impact of diagnostic tests on a patient's health-related quality
      of life (HRQL). METHODS: An influence diagram is used to model how non-ulcer
      dyspepsia (NUD) and its medical care affect HRQL. Diagnostic tests and medical
      therapy benefit HRQL by alleviating fear of disease and NUD symptoms. Medical
      care can also adversely affect HRQL, lead to expenses in time and money, and
      compromise a patient's sense of autonomy. HRQL is modeled as the focal point of
      multiple influences detracting from its value. RESULTS: Negative diagnostic tests
      can improve HRQL in NUD. The improvement of HRQL by diagnostic tests depends on a
      multitude of individual influences and the interactions between them, such as the
      severity of NUD symptoms andfear of disease, as well as the impact of medical
      care itself on HRQL. If a patient harbors a strong fear of serious disease or
      cancer, more extensive testing is likely to improve the patient's well-being and
      appears a worthwhile endeavor. Other patients, however, would be served perfectly
      well by empirical therapy only. For the vast majority of subjects with NUD who
      never seek medical advice, the unpleasantness of the disease itself does not
      outweigh the anticipated downside of obtaining medical care. CONCLUSION: The
      analysis illustrates the applicability of the influence diagram in modeling
      disease behavior. This method helps to assess the benefit of negative tests
      beyond their means of generating information.

PMID- 12058778
TI  - Reduction mammaplasty: defining medical necessity.
AB  - The authors evaluated existing and new criteria for defining the medical
      necessity for breast reduction surgery. Two cohorts of women (those requesting
      breast reduction surgery [N = 266] and a group of controls [N = 184]) completed a
      questionnaire including breast-specific symptom severity, the Short Form 36, the
      EuroQol, the McGill Pain Questionnaire, and the Multidimensional Body Self
      Relations Questionnaire. To evaluate prediction validity, the most widely
      accepted decision criteria and a new definition of medical necessity were applied
      to the data set to determine whether women meeting the definition had more
      favorable outcomes than those who did not as measured by validated self-report
      instruments. For existing criteria, women not meeting and meeting the criterion
      gained equal benefit from surgery. Women meeting the new definition (> or = 2 of
      7 physical symptoms all or most of the time) had significantly greater
      improvement scores on 4 of the 5 health burden measures compared to women not
      meeting this definition. The authors conclude that medical necessity for breast
      reduction surgery is better defined by self-report of symptoms than by existing
      criteria.

PMID- 12058779
TI  - Assessing the sensitivity of decision-analytic results to unobserved markers of
      risk: defining the effects of heterogeneity bias.
AB  - An important assumption made when constructing a Markov model is that all persons
      residing in a health state are identical. Failure to adjust for population
      heterogeneity caused by unobserved variables can therefore cause bias in model
      results. The authors used a simple model to evaluate the potential impact of
      heterogeneity bias, defined as the percentage change in the life expectancy gain
      with an intervention predicted by a model that does not adjust for heterogeneity
      (unadjusted model) compared to one that does (adjusted model). The life
      expectancy gains were consistently greater in the unadjusted model compared to
      the adjusted model (positive bias). For an annual probability of developing
      disease of 1%, the heterogeneity bias exceeded 50% when the relative risk of
      disease with the heterogeneity factor versus without the factor was greater than
      15 and the prevalence of the heterogeneity factor was between 5% and 25%. When
      constructing decision-analytic models, analysts need to be cognizant of
      unobserved factors that introduce heterogeneity into the cohort. This analysis
      provides a general framework to determine when issues of heterogeneity may be
      important.

PMID- 12058780
TI  - Determining sensitivity of mammography from screening data, cancer incidence, and
      receiver-operating characteristic curve parameters.
AB  - OBJECTIVES: A mathematical model is presented that allows the computation of the
      sensitivity and specificity of breast screening based on receiver-operating
      characteristic (ROC) curve shape, the positive predictive value (PPV) of
      screening mammography, and the cancer incidence, f. METHODS: The normal and
      cancer populations are modeled as normal distributions with independent means and
      standard deviations. The distributions are scaled such that the area of the
      normal population is equal to 1-f and that of the cancer population is f. The PPV
      for screening mammography is used to determine the operating point on the ROC
      curve. Knowing this leads directly to the computation of sensitivity and
      specificity. The derivation is general and is applicable to both symmetrical and
      asymmetrical ROC curves. RESULTS: For symmetric ROC curves and typical values for
      the PPV of mammography (about 8%) and cancer incidence (f= 0.003), an A(z) value
      of 0.95 was required to achieve 63% sensitivity and an A. value of 0.98 led to
      86% sensitivity. CONCLUSION: A model was developed that should allow researchers
      to deduce sensitivity and specificity for screening mammography based on ROC
      curve measurements and using realistic values of PPV and f. This model allows A.
      values to be related to the probability of breast cancer detection.

PMID- 12058781
TI  - Visual illusions created by survival curves and the need to avoid potential
      misinterpretation.
AB  - Randomized clinical trials play an increasingly important role in guiding
      management decisions, and survival curves are the most popular means for
      summarizing and depicting the results of a clinical trial. However, survival
      curves may create certain "visual illusions" that can be misinterpreted by the
      unwary, with potentially adverse effects on patient care. The authors provide a
      brief outline of the theoretical background of survival curves and explain the
      origin of the most common visual illusions. Statisticians need to be aware of
      such potential for misinterpretation of clinical trial data in order to safeguard
      clinicians against drawing undue inferences and applying them to actual practice.

PMID- 12058782
TI  - Using elicitation techniques to estimate the value of ambulatory treatments for
      major depression.
AB  - Estimating the value of spending on medical treatments in a health care system
      involves relating output, measured in terms of effectiveness, to cost, measured
      in terms of spending. Although information on spending at the system level often
      exists in administrative data, such as insurance claims, information on
      effectiveness is not always available. An inferential tool available to
      researchers in this context is elicitation. The authors develop an approach to
      elicit effectiveness parameters and apply it to a panel of 10 experts to estimate
      predictive Hamilton Depression Rating Scale scores representing postambulatory
      treatment outcomes. The elicited parameters are used to estimate outcomes
      associated with 120 acute phase treatments for major depression within a
      privately insured health insurance system. The outcome-adjusted price per full
      remission episode is estimated for each acute treatment, and corresponding 95%
      percentile bootstrap intervals are calculated. The average spending for all
      observed treatments was $473 (SE = 478), with a depression-free adjusted price
      per case of $5,995 (95% confidence interval = $5,959-$6,031).

PMID- 12058783
TI  - The role of physicians' recommendations in medical treatment decisions.
AB  - BACKGROUND: A shift away from the medical paternalism of the past has occurred,
      and today, the law and ethics advocate that physicians share decision-making
      responsibility with their patients. It is unclear, however, what the appropriate
      role of physicians' recommendations ought to be in this new shared decision
      making paradigm. One way to approach this question is to assess the influence of
      physicians' recommendations. OBJECTIVE: In this study, the authors examine the
      influence of physicians' recommendations on hypothetical treatment decisions. Do
      physicians' recommendations influence treatment decisions in scenarios where the
      decision that maximizes health is obvious and apparent to subjects? Do
      recommendations pull subjects away from the treatment choice that they otherwise
      prefer (based on their decision when unaware of the physicians' recommendation)?
      DESIGN: An experimental web questionnaire presented hypothetical medical
      treatment scenarios in which the treatment choice that maximized health was
      obvious. Across scenarios, the authors varied physicians' recommendations in 3
      ways: (1) physicians' recommendations supporting what maximized health, (2)
      physicians' recommendations that went against what maximized health, and (3) no
      physicians' recommendation. The participants were 102 volunteers. RESULTS:
      Hypothetical treatment decisions were significantly influenced by
      physicians'recommendations (P < 0.0001), and physicians'recommendations against
      the decision that maximized health pulled subjects away from the treatment
      decision that they made when no recommendation was given (P < 0.0001).
      CONCLUSION: Physicians' recommendations can lead people to make decisions that go
      against what is best and against what they would otherwise prefer. Physicians
      must take care in making recommendations and should incorporate patient
      preferences into their recommendations.

PMID- 12058785
TI  - Law and ethics. The Internet, privacy, and fair information and the question of
      trust in scientific trials.

PMID- 12058784
TI  - "You're perfect for the procedure! Why don't you want it?" Elderly arthritis
      patients' unwillingness to consider total joint arthroplasty surgery: a
      qualitative study.
AB  - OBJECTIVE: To explore the process by which elderly persons make decisions about a
      surgical treatment, total joint arthroplasty (TJA). METHODS: In-depth interviews
      with 17 elderly individuals identified as potential candidates for TJA who were
      unwilling to undergo the procedure. RESULTS: For the majority of participants,
      decision making involved ongoing deliberation of the surgical option, often
      resulting in a deferral of the treatment decision. Three assumptions may
      constrain elderly persons from making a decision about surgery. First, some
      participants viewed osteoarthritis not as a disease but as a normal part of
      aging. Second, despite being candidates for TJA according to medical criteria,
      many participants believed candidacy required a level of pain and disability
      higher than their current level. Third, some participants believed that if they
      either required or would benefit from TJA, their physicians would advise surgery.
      CONCLUSION: These assumptions may limit the possibility for shared decision
      making. CLINICAL IMPLICATIONS: Emphasis should be directed toward thinking about
      ways in which discussions about TJA might be initiated (and by whom) and
      considering how patients' views on and knowledge of osteoarthritis in general
      might be addressed.

PMID- 12058786
TI  - Coronary angiography is still alive and well.

PMID- 12058787
TI  - Reevaluating the role of phosphodiesterase inhibitors in the treatment of
      cardiovascular disease.
AB  - First developed for clinical use in the late 1980s, the phosphodiesterase
      inhibitors were found to increase the levels of the ubiquitous second messenger
      cyclic adenosine monophosphate and could effect changes in vascular tone, cardiac
      function, and other cellular events. After several early studies using high doses
      of phosphodiesterase inhibitors in patients with severe heart failure suggested
      adverse consequences, they fell out of favor. However, recent investigations of
      phosphodiesterase inhibitors in patients with intermittent claudication have
      demonstrated profound benefits. Furthermore, these agents have proven useful in
      prevention of cerebral infarction and coronary restenosis, and their use in the
      treatment of heart failure is being reevaluated. The reemergence of
      phosphodiesterase inhibitors can be attributed to a better understanding of
      dosing and drug-specific pharmacology, the use of concomitant medications, and a
      recognition of unique ancillary properties; however, their use still requires
      caution.

PMID- 12058788
TI  - Use of adenosine as a diagnostic tool for dual atrioventricular nodal pathways:
      response of control patients to incremental doses of adenosine.
AB  - BACKGROUND: Adenosine at low doses preferentially blocks fast over slow pathway
      conduction in patients with dual atrioventricular (AV) nodal physiology and
      typical AV nodal reentrant tachycardia (AVNRT). During atrial pacing, this effect
      is manifested as an abrupt increase in the AH interval with low doses of
      adenosine. This demonstration of dual AV nodal physiology may be useful as a
      diagnostic tool during electrophysiologic studies in patients with
      supraventricular tachycardia who are not easily inducible, as clear demonstration
      of dual AV nodal pathways may indicate that AVNRT is a likely diagnosis and that
      further attempts at arrhythmia induction should be tailored in that direction.
      However, to be a useful test, adenosine should not cause an abrupt increase in AH
      interval in patients without dual AV nodal physiology. HYPOTHESIS: This study was
      designed to investigate the prevalence of dual AV nodal pathways with
      administration of adenosine in patients with no history suggestive of AVNRT.
      METHODS: Thirty-seven patients who had no prior history of AVNRT and were
      undergoing electrophysiologic study for standard indications were enrolled.
      Baseline Wenckebach cycle length (WCL) and AV nodal effective refractory periods
      were measured at atrial pacing cycle lengths of 400 and 600 ms. The atrium was
      then paced at WCL + 50 ms, and WCL + 100 ms, while incrementally larger doses of
      intravenous adenosine were administered until AV nodal block occurred. RESULTS:
      The mean (+/- standard deviation) doses of adenosine required to cause AV nodal
      block while pacing at WCL + 50 ms and WCL + 100 ms were 7.1 +/- 3.9 and 7.4 +/-
      4.5 mg, respectively. In 1 of 37 patients (2.7%, 95% confidence interval 0-8%),
      an abrupt prolongation of the AH interval was seen with the administration of
      adenosine during atrial pacing as well as during the atrial refractory period
      determination. In all other patients, no dual AV nodal physiology was
      demonstrated during the refractory period determination, and there were only
      gradual changes in the AH interval with atrial pacing during administration of
      adenosine. CONCLUSION: Among patients with no history suggestive of AV nodal
      reentrant tachycardia, only 2.7% have clinically silent dual AV nodal pathways
      using this method. Incremental adenosine infusion during electrophysiologic study
      can be used as a highly specific diagnostic tool for patients with dual AV nodal
      pathways.

PMID- 12058789
TI  - Comparison between transesophageal echocardiography and transthoracic
      echocardiography with harmonic tissue imaging for left atrial appendage
      assessment.
AB  - BACKGROUND: Transesophageal echocardiography (TEE) is the method of choice for
      evaluating both anatomy and function of left atrial appendage (LAA). In contrast,
      conventional transthoracic echocardiography (TTE) does not result in images of
      sufficient quality to explore LAA. HYPOTHESIS: The aim of this study was to
      evaluate the potential role of TTE with harmonic frequency imaging (HFI) for
      assessing LAA normal anatomy and function. METHODS: The study group comprised 25
      patients, (9 men, 16 women, mean age 51 years, range 20-82). The TTE as sessment
      of LAA both in fundamental frequency imaging (FFI) and HFI was performed using
      the apical two-chamber view, the longitudinal two-chamber view was used for TEE
      assessment of LAA. According to image quality, images were categorized into three
      classes: A: good quality, B: sufficient quality, C: poor quality. RESULTS:
      Transthoracic echocardiography conventional imaging allowed sufficient LAA
      visualization (class B) in only 5 of 25 patients (20%); the HFI resulted in
      adequate LAA visualization in 23 of 25 patients (92%). Images were of good
      quality (class A) in 18 of 23 patients and of sufficient quality (class B) in 5
      of 23 patients. Transesophageal echocardiography achieved good quality images in
      24 of 25 patients (96%). Average LAA maximum area determined by HFI and TEE was
      3.46 +/-1.17 and 3.59 +/- 1.16 cm2, respectively; LAA minimum area was 1.81 +/-
      0.98 and 1.77 +/- 0.97 cm2, respectively. Percent LAA area change was 51 +/- 16.5
      and 50.9 +/- 16% with HFI and TEE, respectively. Statistical analysis showed no
      difference between the data obtained with the two methods. CONCLUSIONS: The
      results suggest that HFI TNE may be a useful tool for the exploration of LAA.

PMID- 12058790
TI  - The effect of intracoronary fibroblast growth factor-2 on restenosis after
      primary angioplasty or stent placement in a pig model of atherosclerosis.
AB  - BACKGROUND: Therapeutic angiogenesis, if combined with primary percutaneous
      transluminal coronary angioplasty or stent placement, could improve the outcome
      of patients suffering from multifocal coronary disease. HYPOTHESIS: Because of
      the concern that angiogenic growth factors might promote restenosis, we studied
      the effect of a single intracoronary administration of recombinant fibroblast
      growth factor (rFGF)-2 on restenosis after balloon angioplasty and stent
      placement in a pig model of coronary atherosclerosis. METHODS: In 24 Yucatan
      minipigs, coronary lesions were induced by arterial injury and 3 months of
      atherogenic diet. After 3 months, repeat catheterization was performed with
      balloon dilation or stent placement at the injured sites, with a follow-up of 6
      weeks. Results were monitored using quantitative angiography, intravascular
      ultrasound (IVUS), and histomorphometry. RESULTS: Intracoronary rFGF-2 2
      microg/kg did not affect neointima formation or remodeling in this model. A small
      but significant aggravation of late lumen loss was observed in the reference
      segments of the rFGF-2-treated group. Angiographic and echographic late lumen
      loss, intimal hyperplasia, and arterial remodeling, as well as histologic
      neointima were all similar in the rFGF-2- and the vehicle-treated group.
      Confirming earlier studies from our group and those of others, stented arteries
      compared with balloon-dilated arteries had increased angiographic late lumen
      loss, a trend toward increased intimal hyperplasia and decreased remodeling.
      CONCLUSION: We conclude that rFGF-2 does not aggravate restenosis after balloon
      dilation or stenting in this pig model of coronary atherosclerosis. Future
      combinations of angioplasty and therapeutic angiogenesis in a single session
      should be pursued as a feasible and safe strategy.

PMID- 12058791
TI  - Rescue percutaneous coronary intervention following coronary artery bypass graft-
      a descriptive analysis of the changing interface between interventional
      cardiologist and cardiac surgeon.
AB  - BACKGROUND: Despite decreasing rates of acute and subacute complications of
      percutaneous coronary intervention (PCI), these procedures are generally only
      performed in centers where it is possible for failed PCI to be treated by rescue
      coronary artery bypass graft (CABG). Case reports and case series have documented
      successful PCI following failed CABG. We sought to confirm this decrease in the
      need for rescue CABG following failed PCI and to examine trends in the
      utilization of rescue PCI following failed CABG. HYPOTHESIS: The interface
      between interventional cardiologist and cardiac surgeon is characterized by
      changing practice patterns and resource utilization. METHODS: We examined the
      medical records of all patients admitted to the Brigham and Women's Hospital over
      a 7-year period and identified 169 patients who required both PCI and CABG during
      the same hospital admission. We describe and compare three predetermined groups
      of patients defined by the sequence of, and indication for, the relevant
      myocardial revascularization procedures. RESULTS: In all, 100 patients required
      CABG for failed PCI, 46 patients had planned hybrid procedures involving both
      CABG and PCI, and 23 patients required PCI following failed CABG. There was a
      decrease in the need for rescue CABG following failed PCI, both in total numbers
      and as a percentage of total cases (2.5% in 1994 and 0.22% in 1999). There was a
      simultaneous increase in the utilization of rescue PCI following failed CABG (0%
      in 1994 and 1.6% in 2000). Hybrid procedures were identified as a source of
      innovative solutions to a variety of challenging clinical problems. CONCLUSIONS:
      Changing patterns of resource utilization should be considered when planning
      hospital facilities and patient triage, and these patients undergoing
      percutaneous or surgical revascularization may benefit from close cooperation
      between the cardiac surgeon and the interventional cardiologist.

PMID- 12058792
TI  - Lipoprotein(a) was an independent predictor for major coronary events in treated
      hypertensive men.
AB  - BACKGROUND AND HYPOTHESIS: Lipoprotein(a) may play a part in the development of
      coronary heart disease. The purpose of this prospective study was to evaluate
      lipoprotein(a) as a predictor of major coronary events (fatal and nonfatal
      myocardial infarction and sudden death). METHODS: This was a prospective study of
      118 men, aged 56 to 77 years, with treated hypertension and at least one
      additional cardiovascular risk factor (hypercholesterolemia, diabetes mellitus,
      or smoking) were included in the study. Lipoprotein(a) was measured at entry and
      major coronary events were followed during follow-up. RESULTS: The mean
      observation time was 3.0 years. Fourteen patients had a major coronary event
      during the follow-up period. Subjects with coronary heart disease (previous
      myocardial infarction, angina pectoris, or major electrocardiographic changes) at
      entry (n = 27) had significantly higher lipoprotein(a) levels than subjects
      without (n = 91) known coronary heart disease (p < 0.05). Lipoprotein(a) was a
      significant predictor for major coronary events (p = 0.033). Furthermore, when
      coronary disease at entry was included into the Cox regression analysis,
      lipoprotein(a) was an independent predictor for major coronary events (p =
      0.044). CONCLUSIONS: Among treated hypertensive men, lipoprotein(a) was an
      independent predictor of major coronary events.

PMID- 12058793
TI  - Short- and long-term changes of flow-mediated vasodilation in patients under
      statin therapy.
AB  - BACKGROUND: Flow-mediated vasodilation (FMD) of the brachial artery (BA) has been
      shown to improve in response to lipid-lowering therapy and other therapeutic
      interventions, usually within 1 to 2 months. Whether FMD remains improved under
      therapy in the longer term is unknown. HYPOTHESIS: The aim of this study was to
      examine the short- and long-term changes of FMD under statin therapy. METHODS:
      Flow-mediated vasodilation and nitroglycerin-mediated vasodilation (NMD) of the
      BA were measured with high-resolution ultrasound (13 MHz) at baseline and at 4
      and 10 months in 18 consecutively recruited patients with coronary artery disease
      (CAD), in whom statin therapy was newly established. RESULTS: The decrease of
      total plasma cholesterol levels after 4 and 10 months of statin therapy (243 +/-
      31 vs. 186 +/- 30 vs. 191 +/- 40 mg/dl; p < 0.001) was accompanied by an increase
      in FMD from 4.4 +/- 3.8% at baseline to 9.6 +/- 2.7% at 4 months and to 9.5 +/-
      2.6% at 10 months (p < 0.001). Nitroglycerin-mediated vasodilation showed a trend
      toward improvement after 4 months (14.6 +/- 7.5 vs. 19.1 +/- 3.6 vs. 19.4 +/-
      5.6%; NS). The FMD/NMD ratio also rose significantly after 4 months and remained
      improved after 10 months of statin therapy (0.31 +/- 0.25 vs. 0.52 +/- 0.16 vs.
      0.50 +/- 0.14; p < 0.01). CONCLUSION: Statin therapy is associated with sustained
      improvement of endothelial function up to 10 months. These data support the
      utility of FMD for the assessment of vascular function in response to lipid
      lowering therapy or other therapeutic interventions in long-term studies.

PMID- 12058794
TI  - Potential for use of pulse wave analysis in determining the interaction between
      sildenafil and glyceryl trinitrate.
AB  - BACKGROUND: The early part of the central aortic pressure pulse, with amplitude
      (PI - Pd), is generated by left ventricular ejection, while the latter part (or
      augmented pressure), with amplitude (Ps - Pi), is generated by the reflected wave
      arriving during systole. The effects of arterial vasodilator agents, especially
      nitrates, on central aortic systolic blood pressure are grossly underestimated by
      sphygmomanometric measurements of brachial artery pressure. HYPOTHESIS: The
      objective of this study was to investigate the potential for use of central
      arterial pulse wave analysis, obtained noninvasively from the radial pulse, in
      determining the interaction between sildenafil and the nitric oxide donor drug
      glyceryl trinitrate (GTN). METHODS: Central aortic pressure waveforms were
      generated from noninvasively measured radial artery pressure wave-forms and
      subjected to pulse wave analysis to determine the interaction between sildenafil
      and transdermally applied GTN. RESULTS: Transdermal GTN (2.5, 5.0, and 15 mg per
      24-h patches) alone caused no consistent change in sphygmomanometer-determined
      systolic or diastolic pressures, but there was a consistent, dose-related fall in
      amplitude of the augmented systolic pressure, (Ps - Pi), of 4.0, 7.0, and 11
      mmHg, respectively, with little change in diastolic pressure. The 2.5 mg patch
      caused a fall of 4.0 mmHg in aortic systolic pressure, while augmentation index
      (AIx) fell from 20 to 11% and pulse pressure fell 18%. When oral sildenafil (50
      mg) was administered after GTN (2.5 mg), aortic systolic pressure fell another
      4.0 mmHg. This decrease in systolic pressure caused a fall in AIx to almost 0.0%;
      pulse pressure fell another 9.0%. CONCLUSION: These modifications in aortic
      systolic and pulse pressure are due primarily to reduction in wave-reflection
      amplitude and are not detected by sphygmomanometer-measured brachial artery
      pressure.

PMID- 12058795
TI  - Images in Cardiology: Inappropriate firing of an implantable cardioverter
      defibrillator due to 60 cycle noise.

PMID- 12058796
TI  - Primary (isolated) meningococcal pericarditis.
AB  - A 19-year-old man was admitted with a history and examination findings of
      probable bacterial pericarditis. Blood cultures produced Neisseria meningitidis
      Group C, sensitive to penicillin. The patient was initially treated with
      intravenous benzylpenicillin. Echocardiogram demonstrated the development of a
      pericardial effusion which was tapped, and benzylpenicillin was instilled into
      the pericardial space. Because of failure of clinical resolution, cefotaxime was
      substituted for benzylpenicillin. Rapid clinical improvement then ensued. Repeat
      echocardiogram showed evidence of neither reaccumulation nor constrictive
      pericarditis. Primary (isolated) meningococcal pericarditis is a recognized
      though rare manifestation of meningococcal disease. It is most common in young
      adults and is associated with a good prognosis.

PMID- 12058797
TI  - Dennis V. Cokkinos.

PMID- 12058798
TI  - Prevalence of exposure to environmental tobacco smoke at work and at home--15
      year trends in Finland.
AB  - OBJECTIVES: This study describes the 15-year trends of exposure to environmental
      tobacco smoke at work and at home in Finland. METHODS: A postal survey was made
      annually from 1985 to 2000. It included a random sample of 58,721 Finnish men and
      women aged 15 to 64 years. RESULTS: In the middle of the 1980s, about a quarter
      of employed nonsmoking men and 15% of nonsmoking women were exposed at least 1
      hour daily to environmental tobacco smoke at work. In 2000, the proportions were
      7.9% and 4.4%, respectively. Exposure to environmental tobacco smoke at home
      decreased also slightly. In 2000, 14.3% of the nonsmoking men and 13% of the
      nonsmoking women aged 15 to 64 years were exposed to environmental tobacco smoke
      either at work or at home. Exposure at work was about three times more common
      among smokers than among nonsmokers, but a decreasing trend was also found among
      smokers. In 2000, in 85% of workplaces smoking was permitted only in separate
      smoking rooms, or no one was smoking within the work environment. On the other
      hand, in 7.3% of workplaces smoking was permitted also in common areas.
      CONCLUSIONS: In the past 15 years, exposure to environmental tobacco smoke at
      work decreased significantly in Finland. Both legislative actions and the general
      decrease in smoking prevalence have contributed to this decline. However, despite
      the marked decrease, nearly 14% of nonsmokers aged 15 to 64 years are still
      exposed to environmental tobacco smoke, either at home or in the workplace.

PMID- 12058799
TI  - Biomarkers in the assessment of exposure and the biological effects of
      environmental tobacco smoke.
AB  - Environmental tobacco smoke is one of the most widespread carcinogenic exposures.
      Given the substantial numbers daily exposed to this substance and the great
      amount of scientific data on its association with chronic diseases, accurate
      measurements of its exposure, intake, and biological effects are needed. In fact,
      studies exploiting various kinds of biomarkers are crucial in increasing the
      understanding of the biological processes and mechanisms of the adverse health
      effects related to exposure, as well as in adding biological plausibility to the
      existing epidemiologic evidence. This paper summarizes data on known biomarkers
      currently in use in human population studies for detecting exposure, the
      biologically effective dose, the biological effects, or the disease processes
      related to environmental tobacco smoke. Of the biomarkers discussed, cotinine is
      currently well suited for assessing the exposure and intake of environmental
      tobacco smoke, while urinary metabolites of tobacco-specific nitrosamines appear
      to serve as sensitive markers for the uptake and metabolism of carcinogenic
      constituents of environmental tobacco smoke.

PMID- 12058800
TI  - Environmental tobacco smoke--a major preventable cause of impaired health at
      work.

PMID- 12058801
TI  - Involuntary smoking and lung cancer.
AB  - Involuntary smoking contains human carcinogens. Exposure prevalence among adults
      is on the order of 40%. A meta-analysis of epidemiologic studies on lung cancer
      and exposure to involuntary smoking from the spouse included 51 studies. The
      overall relative risk (RR), based on 7369 cases of lung cancer, was 1.25 [95%
      confidence interval (95% CI) 1.15-1.37]. No evidence existed of an RR difference
      between the two genders, and study design had no influence on the results. The
      summary RR was lower for adenocarcinoma than for other histological types. In the
      largest studies cumulative exposure suggested a dose-response relationship with a
      unit risk of similar magnitude. The summary RR was 1.17 (95% CI 1.04-1.32) for
      workplace exposure. Several sources of bias may lead to both overestimation and
      underestimation of true association, and the most plausible interpretation favors
      a causal association. Even if excess risk from exposure to involuntary smoking is
      small, its large prevalence makes it an important environmental carcinogen.

PMID- 12058802
TI  - Environmental tobacco smoke and the risk of cardiovascular disease.
AB  - Disease risk due to smoking is not limited to smokers only. Passive smoking,
      exposure to environmental tobacco smoke, is associated with adverse health
      effects, and it increases the risk of several diseases. This paper summarizes the
      cardiovascular effects of tobacco smoke and the current data on the effects of
      environmental tobacco smoke on the development of cardiovascular disease.
      According to the results of epidemiologic and experimental studies, environmental
      tobacco smoke has marked harmful effects on the cardiovascular system. It is
      estimated that it increases the risk of an acute event of coronary heart disease
      by 25-35%. Even though the number of studies conducted in the work environment is
      small, there is no reason to assume that the cardiovascular effects of
      environmental tobacco smoke differ markedly between the home and the workplace.
      Firm and timely actions are needed to protect people from exposure to
      environmental tobacco smoke, both in occupational and other environments.

PMID- 12058803
TI  - Effects of environmental tobacco smoke on the respiratory health of adults.
AB  - In this paper, current knowledge on the respiratory effects of environmental
      tobacco smoke among adults is synthesized, and the biological basis and
      methodological issues are discussed. The Medline database was searched from 1966
      through October 2000. All of the related respiratory effects have been linked to
      both home and workplace exposures. Some evidence of a dose-response relation has
      also been detected for all respiratory conditions. The strongest evidence of a
      causal relation exists for chronic respiratory symptoms. Harmful effects on lung
      function have also been detected, mainly in countries and occupations with high
      exposure levels. There is limited evidence indicating an increased risk of its
      causing asthma and chronic obstructive pulmonary disease, and also for poor
      control of established asthma. More longitudinal studies with careful assessment
      of exposure are needed for better risk estimates. Despite these challenges for
      the future, the combination of toxicologic evidence, abundant evidence on
      respiratory effects among children, and the studies reviewed in this paper point
      to an urgent need for measures to prevent exposure to environmental tobacco smoke
      among adults.

PMID- 12058804
TI  - Exposure to environmental tobacco smoke in Finland in 2000.
AB  - OBJECTIVES: Exposure to environmental tobacco smoke at workplaces, homes and
      other places was assessed. METHODS: Exposure to environmental tobacco smoke was
      defined as occurring when a person reported inhaling, at least occasionally,
      tobacco smoke from other people's smoke. Some of the exposed were also smokers
      themselves. Questionnaire-based survey data and industrial hygiene measurements
      on environmental tobacco smoke were used to estimate the numbers of exposed
      persons by exposure level in Finland in January 2000. RESULTS: About 340,000
      workers (16% of the employed population) were exposed to environmental tobacco
      smoke at work, of them 30,000 were exposed almost continuously (1.4% of the
      employed population). The mean level of exposure was 1 microg/m2 as measured by
      nicotine in workroom air. The nicotine concentration ranged from < 1 to > 100
      microg/m3. Nearly 600,000 Finns (1% of the population) were exposed to
      environmental tobacco smoke at home. According measurements abroad, their mean
      nicotine exposure corresponded to about 4 microg/m3 at work. In addition, over 1
      million Finns were exposed during leisure time to an unknown mean level of
      environmental tobacco smoke. Annual exposure of the Finnish population in January
      2000 was estimated to originate mainly from smoking at home (48%) and leisure
      time in smoky restaurants (45%). Smoking was restricted at workplaces in 1995 and
      occupational exposure constituted 7% of the total population exposure in January
      2000. New restrictions on smoking in restaurants should decrease the exposure of
      restaurant workers and customers even further. CONCLUSIONS: In spite of
      regulations, environmental tobacco smoke still remains the most common
      occupational exposure to chemical carcinogens in Finland.

PMID- 12058805
TI  - Effects of environmental tobacco smoke on the respiratory health of children.
AB  - This review synthesizes current knowledge of the effects of prenatal and
      postnatal exposure to environmental tobacco smoke on the respiratory health of
      children. A Medline database search was conducted for 1966 through October 2000.
      Limited evidence was found that exposure in pregnancy influences fetal growth,
      increases the risk of preterm delivery, and predicts the development of asthma
      and reduced lung function later in life. Both occupational and home environments
      contribute to the exposure of pregnant women and thus indirectly to adverse
      effects on children. There is strong and consistent evidence that exposure in
      childhood causes chronic respiratory symptoms (eg, cough, phlegm, and wheezing)
      and induces asthma. Limited evidence supports the role of childhood exposure in
      the poor overall control of established disease. Postnatal exposure is likely to
      have a small adverse impact on lung function growth. Prenatal and postnatal
      exposures have an important impact on children's respiratory health. These
      effects are preventable if pregnant women and children are protected from
      exposure to environmental tobacco smoke.

PMID- 12058806
TI  - Effects of exposure to environmental tobacco smoke on reproductive health.
AB  - The scientific evidence on the effects of preconceptional and prenatal exposure
      to environmental tobacco smoke on reproductive health is reviewed in this
      article. The evidence is the most convincing for the adverse effects of
      environmental tobacco smoke on birthweight. In meta-analyses, exposure to
      environmental tobacco smoke has been estimated to reduce mean birthweight by
      about 25-40 grams. The majority of the studies on low birthweight also show a
      moderately or slightly increased risk among infants of exposed women. There is
      also some support for an association between high exposure to environmental
      tobacco smoke and preterm birth. The evidence on the effects of environmental
      tobacco smoke on spontaneous abortion and birth defects is weak and inconsistent.
      Very little is known about the impact of exposure on fertility, menstrual
      function, reproductive health of men, and childhood cancer. Further studies,
      paying attention to study design and careful exposure assessment, are therefore
      needed on these associations.

PMID- 12058807
TI  - Influence of processing conditions in the manufacture of O/W creams: I. Effect on
      dispersion grade and rheological characteristics.
AB  - Two series of O/W creams having the same general formulation were prepared in
      three different mechanical conditions (F with an hand blender; S with a
      turbomixer; T with a vacuum turbo emulsor) using two types of surfactants,
      polyoxyethylene-cetostearyl alcohols and polyglyceryl-3-methylglucose-distearate.
      By means of microscopic image analysis it was possible to point out the
      dispersion grade of the oil internal phase increasing with the energy applied
      under the conditions of manufacture (F < S < T). The level of dispersion
      influenced significantly on the rheological characteristics of the creams. With
      polyoxyethylene-cetostearyl alcohols, the viscosity of creams increased as the
      energy applied in manufacturing increased, with polyglyceryl-3-methylglucose
      distearate on the contrary decreased. Moreover, indifferently to the
      manufacturing conditions, even in the same concentration of surfactant, the
      creams obtained with the last produced a much greater viscosity. At a parity of
      manufacturing conditions the differences between the batches of productions were
      not significant.

PMID- 12058808
TI  - Influence of processing conditions in the manufacture of O/W creams: II. Effect
      on drug availability.
AB  - O/W creams prepared in three mechanical conditions (F with a hand blender; S
      turbomixer; T vacuum turbo-emulsor) produced different dispersion grades of the
      internal phase and different rheological characteristics by using surfactants of
      different chemical nature (polyoxyethylene-cetostearyl alcohols and polyglyceryl
      3-methylglucose distearate). Three tests were used (an in vitro release test
      across a porous membrane; an in vitro simulated absorption test across a porous
      membrane impregnated with isopropyl myristate; an in vivo absorption test based
      on the intensity and duration of the erythema produced by methyl nicotinate after
      application of the cream on the skin) to assess whether the different physical
      characteristics influence drug availability from the creams. The different
      physical characteristics due to the mechanical conditions of emulsifying and
      gelification appeared not to influence drug release and in vivo absorption.

PMID- 12058809
TI  - Antimycobacterial activity of 5-arylidene aromatic derivatives of hydantoin.
AB  - Various 5-(chlorobenzylidene)-2-isoniazido and 5-(chlorobenzylidene)-2-amino
      substituted derivatives of imidazoline-4-one were synthesized and evaluated in
      the primary assay for their antimycobacterial activity against Mycobacterium
      tuberculosis H37Rv. Eight of them exhibited > 90% inhibition in the primary
      screening at 12.5 microg/ml. For these primarily selected compounds the actual
      MIC and IC50 values were determined. Two of the isoniazid derivatives, for which
      MIC < 3.13 microg/ml and SI > 10, were selected for further screening and
      investigated for efficacy in vitro in a TB-infected macrophage model. The most
      promising compound, 5-(3-chlorobenzylidene)-2-(isonicotinoylhydrazino)
      imidazoline-4-one, with activity in vitro comparable with rifampin (MIC = 0.8
      microg/ml. SI > 78) was tested in vivo in the animal tuberculosis model but
      exhibited insignificant activity. For several compounds the primary screening of
      antimycobacterial activity against Mycobacterium avium (ATCC 25291) was conducted
      as well, but none of them demonstrated satisfactory activity.

PMID- 12058811
TI  - Determination of triclosan in personal health care products by liquid
      chromatography (HPLC).
AB  - An isocratic reversed-phase liquid chromatographic (HPLC) method is proposed for
      the practical and reliable determination of triclosan, an antimicrobic agent
      incorporated into a variety of personal heath care products. Chromatographic
      separations were performed on a C-18 column using acetonitrile-TEA phosphate (70
      mM; pH 3.5) 55:45 (v/v) as mobile phase and UV detection at 230 and 280 nm. The
      selectivity of the method was assured by the on-line photodiode array detector.
      The identity of the triclosan peak was also confirmed by HPLC MS. The method was
      successfully applied to the determination of triclosan in commercially available
      health care products (deodorant stick, dentifrice gel, mouthrinse, toothpaste and
      handwash). All the products displayed triclosan concentrations in compliance with
      the EEC directive (< or = 0.3%,).

PMID- 12058810
TI  - Synthesis and pharmacological properties of benzisothiazole/benzimidazole
      derivatives with acidic groups.
AB  - The synthesis and the pharmacological evaluation of benzisothiazole and
      benzimidazole tetrazolyl- and carboxyl- derivatives 1-6 are described. Structural
      modification was aimed at investigating the influence of two isosteric
      substituents (tetrazolyl- and carboxyl-) on the title benzofused heterocycles.
      The antiphlogistic, antipyretic and analgesic activities have been investigated
      in in vivo experimental models. Additional investigations have been performed in
      vitro to study the antiplatelet and spasmolytic activity of the compounds
      synthetized. All the compounds produced peripheral analgesic effects, but were
      less effective in hot plate test. The tetrazole and the carboxylic
      benzisothiazole derivatives 2 and 3 proved to be the most effective drugs within
      the series, exhibiting maximal inhibition of writhes with a potency 3-fold higher
      than that of acetaminophen. Only compound 5 provided indication for a central
      analgesic activity since it was active in hot plate test although with a low
      potency. The findings obtained in these in vivo and in vitro studies indicate
      that these compounds do not share the same mechanism of action of acetaminophen.
      All of the compounds under study present lower acute toxicity than acetaminophen
      when orally administered in mice.

PMID- 12058812
TI  - Organometallic chemistry on solid phase. An overview.
AB  - Solid-phase organic synthesis (SPOS) is the most important method for the
      production of combinatorial libraries and with the development of high-throughput
      screening, libraries are widespread in pharmaceutical and agricultural chemistry.
      Amongst all the synthetic transformations successfully applied to solid phase,
      the use of organometallic reagents for the formation of a new carbon-carbon bond
      has been scarcely pursued. In this overview we collected the most recent examples
      of the use of organometallic reagents of Li, Mg, Cu, Zn, Si and B for C-C bond
      formation. The use of organometallic reagents in Pd-catalysed cross-coupling
      reactions was not reviewed. Highly basic organometallics as organo-lithium and 
      magnesium reagents have been more largely employed than cuprates and zincates,
      suggesting that several kinds of resins can withstand relatively strong reaction
      conditions.

PMID- 12058813
TI  - The medicinal chemistry of multidrug resistance (MDR) reversing drugs.
AB  - Multidrug resistance (MDR) is a kind of resistance of cancer cells to multiple
      classes of chemotherapic drugs that can be structurally and mechanistically
      unrelated. Classical MDR regards altered membrane transport that results in lower
      cell concentrations of cytotoxic drug and is related to the over expression of a
      variety of proteins that act as ATP-dependent extrusion pumps. P-glycoprotein
      (Pgp) and multidrug resistance protein (MRP1) are the most important and widely
      studied members of the family that belongs to the ABC superfamily of
      transporters. It is apparent that, besides their role in cancer cell resistance,
      these proteins have multiple physiological functions as well, since they are
      expressed also in many important non-tumoural tissues and are largely present in
      prokaryotic organisms. A number of drugs have been identified which are able to
      reverse the effects of Pgp, MRPI and sister proteins, on multidrug resistance.
      The first MDR modulators discovered and studied in clinical trials were endowed
      with definite pharmacological actions so that the doses required to overcome MDR
      were associated with unacceptably high side effects. As a consequence, much
      attention has been focused on developing more potent and selective modulators
      with proper potency, selectivity and pharmacokinetics that can be used at lower
      doses. Several novel MDR reversing agents (also known as chemosensitisers) are
      currently undergoing clinical evaluation for the treatment of resistant tumours.
      This review is concerned with the medicinal chemistry of MDR reversers, with
      particular attention to the drugs that are presently in development.

PMID- 12058814
TI  - Platelet antiaggregatory effects and haemodynamic activity of two terfuroxan
      isomer pairs.
AB  - A couple of terfuroxan isomer pairs 1a,b and 2a,b were studied for their in vivo
      vasodilating activity and in vitro antiplatelet action. The haemodynamic profiles
      of the products resemble that of other NO-donors. Their in vitro antiaggregating
      activity is influenced both by terfuroxan system and by the substituents.

PMID- 12058815
TI  - Synthesis and antimicrobial activities of N-substituted imides.
AB  - In the field of our research programs concerning novel antimicrobial agents, a
      series of N-substituted imides was synthesized. These compounds were obtained by
      cyclization of amido-acids in acetic anhydride/sodium acetate or
      hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The
      hydroxy-alkyl maleimides were directly prepared by condensation of the
      corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N
      substituted maleimides showed an interesting antimicrobial activity towards
      bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus
      faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC
      27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The
      imides with alkyl substituents showed higher activities than aromatic analogues
      with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were
      practically inactive.

PMID- 12058816
TI  - Enhanced acidogenic fermentation of food waste in a continuous-flow reactor.
AB  - This study was performed to improve acidogenic fermentation of food waste in a
      continuous-flow reactor. The fermentation of food waste is affected by the
      fermentation constraints such as the biodegradability of substrate, the degrading
      capability of microorganisms and the environmental conditions. The key factors
      were, therefore, examined to control the fermentation constraints, such as the
      effect of seed inoculation and the effect of adjusting dilution rate. Acidogenic
      fermentation of food waste employing rumen microorganisms resulted in the
      enhanced efficiency (71.2%) as compared with that (59.8%) employing mesophilic
      acidogens. In addition, the fermentation efficiency increased from 71.2 to 82.0%
      by adjusting dilution rate from 3.0 to 1.0 d(-1) depending on the state of the
      fermentation. The main component of the acidified product was shifted from
      butyric to acetic acid. This meant that the increase of the fermentation
      efficiency was mainly caused by the enhanced degradation of vegetables and meats.
      The control of the fermentation constraints was, therefore, very effective in
      improving the fermentation efficiency of food waste.

PMID- 12058817
TI  - Continuous feed, on-site composting of kitchen garbage.
AB  - Kitchen garbage generated at a school cafeteria was treated and stabilised in a
      controlled on-site composting unit for volume reduction and on-site utilisation
      of processed garbage. The on-site composter was fed with the garbage on a daily
      basis during the two-months experimental period. Compost was not removed from the
      unit but was entirely reused as a bulking agent in order to minimise the need for
      additional bulking agent and compost handling. Performance of the composter
      tinder this condition was investigated. Most of the easily degradable organic
      matter (EDM) in the garbage was biodegraded rapidly, and the final product had a
      low content of EDM. Lipids, total sugar, and hemi-cellulose were degraded 96%,
      81%, and 66% respectively. Free air space (FAS) was higher than 0.5 all the time,
      so accumulation of dry matter in the unit was not significant in reducing
      reaction efficiency. Other reaction parameters such as pH and MC were kept within
      a suitable range; however, it was advisable to maintain MC at over 46%. As a
      result, this method of operation was able to stabilise the garbage with low
      sawdust demand and little compost production.

PMID- 12058818
TI  - Vienna's biowaste compost--quality development and effects of input materials.
AB  - Extensive chemical analyses were conducted during the last decade to assess the
      heavy metal content of the finished compost as well as of biowaste and other
      input materials. Twenty six percent of the compost lots were class I according to
      ONORM S2200, 70% class II and 4% did not reach class II. If the compost lots were
      classified according to the new Austrian compost ordinance, 22% would conform to
      class A+ and 78% to class A. These data are put into relation with heavy metal
      contents of soil, of yard wastes and of biowastes without contaminants. In the
      soil samples particularly nickel and lead exceeded the limits for class A+
      (compost ordinance). In the yard wastes, more than 90% of the samples met the
      limits for all heavy metals. Biowaste without contaminants conformed to class A+
      on average. In biowaste without contaminants no influence of the housing
      structure on the heavy metal content was observed. The compost produced only from
      biowaste from areas with high building density, after undergoing the normal
      process of metal removal, however, was significantly higher contaminated than
      that of compost of the whole city of Vienna. The impact of specific input
      materials, such as Christmas trees or wooden crates, was investigated by chemical
      analyses before and after controlled composting experiments with those materials.
      In both experiments the compost quality did not reach the limits for heavy metals
      of class I (ONORM S2200).

PMID- 12058819
TI  - Vermicomposting of a lignocellulosic waste from olive oil industry: a pilot scale
      study.
AB  - The vermicomposting with Eisenia andrei of dry olive cake, a lignocellulosic
      waste produced during the extraction of olive oil, either alone or mixed with
      municipal biosolids, was studied in a nine-month pilot scale experiment. Number
      and biomass of earthworms and enzyme activities were periodically monitored and
      relevant properties of the final products were determined. In the assayed
      substrates, the total biomass of earthworms increased at the end of the
      experimental period between 9 and 12-fold respectively in comparison with the
      earthworm biomass initially inoculated. The increase in hydrolytic enzymes and
      overall microbial activity during the vermicomposting process indicated the
      biodegradation of the olive cake and resulted in the disappearance of the initial
      phytotoxicity of the substrate. However, the recalcitrant lignocellulosic nature
      of the dry olive cake prevented suitable humification during the vermicomposting
      process. For this reason, in addition to organic amendments, other management
      procedures should be considered.

PMID- 12058820
TI  - Plant available nitrogen from anaerobically digested sludge and septic tank
      sludge applied to crops grown in the tropics.
AB  - Agricultural land is an attractive alternative for the disposal of biosolids
      since it utilises the recyclable nutrients in the production of crops. In
      Thailand and other tropical regions, limited field-study information exists on
      the effect of biosolids management strategies on crop N utilisation and plant
      available N (PAN) of biosolids. A field study was conducted to quantify the PAN
      of the applied biosolids, and to evaluate the N uptake rates of some tropical
      crops. Sunflower (Helianthus annuus) and tomato (Lycopersicon esculentum) were
      chosen in this study. Two types of biosolids used were: anaerobically digested
      sludge and septic tank sludge. The soil is acid sulfate and is classified as
      Sulfic Tropaquepts with heavy clay in texture. The anaerobically digested sludge
      applied rates were: 0, 156 and 312 kg N ha(-1) for the sunflower plots, and 0,
      586, and 1172 kg N ha(-1) for the tomato plots. The septic tank sludge applied
      rates were: 0, 95 and 190 kg N ha(-1) for the sunflower plots, and 0, 354 and 708
      kg N ha(-1) for the tomato plots, respectively. The results indicated the
      feasibility of applying biosolids to grow tropical crops. The applications of the
      anaerobically digested sludge and the septic tank sludge resulted in the yields
      of sunflower seeds and tomato fruits and the plant N uptakes comparable or better
      than that applied with only the chemical fertiliser. The estimated PAN of the
      anaerobically digested sludge was about 27-42% of the sludge organic N during the
      growing season. For the septic tank sludge, the PAN was about 15-58% of the
      sludge organic N. It is interesting to observe that an increase of the rate of
      septic tank sludge incorporated into this heavy clay soil under the cropping
      system resulted in the decrease of N mineralisation rate. This situation could
      cause the reduction of yield and N uptake of crops.

PMID- 12058821
TI  - Microbial risk assessment of source-separated urine used in agriculture.
AB  - A screening-level quantitative microbial risk assessment (QMRA) was undertaken
      for a urine separating sewerage system. Exposures evaluated included the handling
      of stored and unstored urine as well as consumption of crops fertilised with
      urine. Faecal cross-contamination was the source of risk and Campylobacter
      jejuni, Cryptosporidium parvum and rotavirus were the organisms chosen to
      represent different groups of enteric pathogens. Accidental ingestion of unstored
      urine implied a high risk (Pinf = 0.56) for infection from rotavirus whereas the
      risks for infection from bacteria and protozoa were approximately 1:10 000. After
      six months storage at 20 degrees C the risk for viral infections by accidental
      ingestion of 1 ml of urine was < 10(-3), the suggested acceptable risk benchmark.
      Ingestion of crops contaminated with urine resulted in risks of < 10(-5) after a
      3-week (<10(-7) after 4 weeks) withholding period between fertilising and
      harvesting.

PMID- 12058822
TI  - Microbial reduction of amended sulfate in anaerobic mature fine tailings from oil
      sand.
AB  - Bitumen extraction from oil sands has resulted in large tailings ponds,
      containing suspended material that requires over one hundred years to densify.
      The mature fine tailings (MFT) have become anaerobic and bubbles of gas are
      observed on the pond surface. Gypsum has been proposed as an additive to increase
      the rate of MFT consolidation. In a laboratory study, MFT was amended with
      sulfate and monitored. Pore water sulfate concentrations declined and bicarbonate
      concentration increased. Nitrate was depleted within 36 d and the levels of
      soluble iron remained below 0.8 mg L(-1). Thiosulfate and sulfide were detected
      only near the end of the experiment. Acid volatile sulfides (AVS) increased until
      day 39, and then reached a plateau. Methane was not detected throughout the
      incubation in samples amended with sulfate. The increase in AVS supports sulfide
      incorporation into the solid phase, however, the plateau after 39 d suggests a
      secondary fate of reduced sulfide.

PMID- 12058823
TI  - The bioreactor landfill: its status and future.
AB  - The bioreactor landfill provides control and process optimisation, primarily
      through the addition of leachate or other liquid amendments. Sufficient
      experience now exists to define recommended design and operating practices.
      However, technical challenges and research needs remain related to
      sustainability, liquid addition, leachate hydrodynamics, leachate quality, the
      addition of air, and cost analysis.

PMID- 12058824
TI  - A Fuzzy Markov approach for assessing groundwater pollution potential for
      landfill siting.
AB  - This study presents a Fuzzy Markov groundwater pollution potential assessment
      approach to facilitate landfill siting analysis. Landfill siting is constrained
      by various regulations and is complicated by the uncertainty of groundwater
      related factors. The conventional static rating method cannot properly depict the
      potential impact of pollution on a groundwater table because the groundwater
      table level fluctuates. A Markov chain model is a dynamic model that can be
      viewed as a hybrid of probability and matrix models. The probability matrix of
      the Markov chain model is determined based on the groundwater table elevation
      time series. The probability reflects the likelihood of the groundwater table
      changing between levels. A fuzzy set method is applied to estimate the degree of
      pollution potential, and a case study demonstrates the applicability of the
      proposed approach. The short- and long-term pollution potential information
      provided by the proposed approach is expected to enhance landfill siting
      decisions.

PMID- 12058825
TI  - Modelling for environmental assessment of municipal solid waste landfills (part
      1: hydrology).
AB  - A three-dimensional dynamic simulation program for the prediction of leachate
      flows, their organic contamination and the gas generated in municipal waste
      landfills, (MODUELO) has been developed. It permits the simulation of canyon
      landfills in which the surface area changes throughout the landfill's history and
      of complex drainage systems. The "hydrologic module" calculates, based on the
      saturated flow equations, the water flow between cells and the overall moisture
      balance. Its results allow the "contamination module" to carry out the balance of
      organic material. This paper presents the development of the "hydrologic module".
      The contamination models are included in another paper. A preliminary application
      to the Meruelo Landfill (Spain) is also shown here. The fitting of a data series
      of leachate flows in Meruelo indicated the existence, in this particular
      landfill, of unconsidered phenomena. The final adjustment of the results makes it
      possible to obtain a reliable simulation of the degradation processes.

PMID- 12058826
TI  - Hydrolysis of lignocellulosic materials for ethanol production: a review.
AB  - Lignocellulosic biomass can be utilized to produce ethanol, a promising
      alternative energy source for the limited crude oil. There are mainly two
      processes involved in the conversion: hydrolysis of cellulose in the
      lignocellulosic biomass to produce reducing sugars, and fermentation of the
      sugars to ethanol. The cost of ethanol production from lignocellulosic materials
      is relatively high based on current technologies, and the main challenges are the
      low yield and high cost of the hydrolysis process. Considerable research efforts
      have been made to improve the hydrolysis of lignocellulosic materials.
      Pretreatment of lignocellulosic materials to remove lignin and hemicellulose can
      significantly enhance the hydrolysis of cellulose. Optimization of the cellulase
      enzymes and the enzyme loading can also improve the hydrolysis. Simultaneous
      saccharification and fermentation effectively removes glucose, which is an
      inhibitor to cellulase activity, thus increasing the yield and rate of cellulose
      hydrolysis.

PMID- 12058827
TI  - Anaerobic digestion of organic solid poultry slaughterhouse waste--a review.
AB  - This work reviews the potential of anaerobic digestion for material recovery and
      energy production from poultry slaughtering by-products and wastes. First, we
      describe and quantify organic solid by-products and wastes produced in poultry
      farming and poultry slaughterhouses and discuss their recovery and disposal
      options. Then we review certain fundamental aspects of anaerobic digestion
      considered important for the digestion of solid slaughterhouse wastes. Finally,
      we present an overview of the future potential and current experience of the
      anaerobic digestion treatment of these materials.

PMID- 12058828
TI  - Advances in poultry litter disposal technology--a review.
AB  - The land disposal of waste from the poultry industry and subsequent environmental
      implications has stimulated interest into cleaner and more useful disposal
      options. The review presented here details advances in the three main alternative
      disposal routes for poultry litter, specifically in the last decade. Results of
      experimental investigations into the optimisation of composting, anaerobic
      digestion and direct combustion are summarised. These technologies open up
      increased opportunities to market the energy and nutrients in poultry litter to
      agricultural and non-agricultural uses. Common problems experienced by the
      current technologies are the existence and fate of nitrogen as ammonia, pH and
      temperature levels, moisture content and the economics of alternative disposal
      methods. Further advancement of these technologies is currently receiving
      increased interest, both academically and commercially. However, significant
      financial incentives are required to attract the agricultural industry.

PMID- 12058829
TI  - Energy production from biomass (Part 1): Overview of biomass.
AB  - The use of renewable energy sources is becoming increasingly necessary, if we are
      to achieve the changes required to address the impacts of global warming. Biomass
      is the most common form of renewable energy, widely used in the third world but
      until recently, less so in the Western world. Latterly much attention has been
      focused on identifying suitable biomass species, which can provide high-energy
      outputs, to replace conventional fossil fuel energy sources. The type of biomass
      required is largely determined by the energy conversion process and the form in
      which the energy is required. In the first of three papers, the background to
      biomass production (in a European climate) and plant properties is examined. In
      the second paper, energy conversion technologies are reviewed, with emphasis on
      the production of a gaseous fuel to supplement the gas derived from the
      landfilling of organic wastes (landfill gas) and used in gas engines to generate
      electricity. The potential of a restored landfill site to act as a biomass
      source, providing fuel to supplement landfill gas-fuelled power stations, is
      examined, together with a comparison of the economics of power production from
      purpose-grown biomass versus waste-biomass. The third paper considers particular
      gasification technologies and their potential for biomass gasification.

PMID- 12058830
TI  - Energy production from biomass (Part 2): Conversion technologies.
AB  - The use of biomass to provide energy has been fundamental to the development of
      civilisation. In recent times pressures on the global environment have led to
      calls for an increased use of renewable energy sources, in lieu of fossil fuels.
      Biomass is one potential source of renewable energy and the conversion of plant
      material into a suitable form of energy, usually electricity or as a fuel for an
      internal combustion engine, can be achieved using a number of different routes,
      each with specific pros and cons. A brief review of the main conversion processes
      is presented, with specific regard to the production of a fuel suitable for spark
      ignition gas engines.

PMID- 12058831
TI  - Energy production from biomass (Part 3): Gasification technologies.
AB  - The conversion of biomass by gasification into a fuel suitable for use in a gas
      engine increases greatly the potential usefulness of biomass as a renewable
      resource. Gasification is a robust proven technology that can be operated either
      as a simple, low technology system based on a fixed-bed gasifier, or as a more
      sophisticated system using fluidized-bed technology. The properties of the
      biomass feedstock and its preparation are key design parameters when selecting
      the gasifier system. Electricity generation using a gas engine operating on gas
      produced by the gasification of biomass is applicable equally to both the
      developed world (as a means of reducing greenhouse gas emissions by replacing
      fossil fuel) and to the developing world (by providing electricity in rural areas
      derived from traditional biomass).

PMID- 12058832
TI  - An economic analysis of biomass gasification and power generation in China.
AB  - With vast territory and abundant biomass resources China appears to have suitable
      conditions to develop biomass utilization technologies. As an important
      decentralized power technology, biomass gasification and power generation (BGPG)
      has a potential market in making use of biomass wastes. In spite of the
      relatively high cost for controlling secondary pollution by wastewater, BGPG is
      economically feasible and can give a financial return owing to the low price of
      biomass wastes and insufficient power supply at present in some regions of China.
      In this work, experimental data from 1 MW-scale circulating fluidized bed (CFB)
      BGPG plants constructed recently in China were analyzed; and it was found that
      the unit capital cost of BGPG is only 60-70% of coal power station and its
      operation cost is much lower than that of conventional power plants. However, due
      to the relatively low efficiency of small-scale plant, the current BGPG
      technology will lose its economic attraction when its capacity is smaller than
      160 kW or the price of biomass is higher than 200 Yuan RMB/ton. The development
      of medium-scale BGPG plants, with capacity ranging from 1000 to 5000 kW, is
      recommended; as is the demonstration of BGPG technology in suitable enterprises
      (e.g. rice mill and timber mill) in developing countries where large amounts of
      biomass wastes are available so that biomass collection and transportation can be
      avoided and the operation cost can be lowered.

PMID- 12058833
TI  - Raising the ceiling: the Tower of London--extended version.
AB  - The Tower of London (TOL) is a neuropsychological test used to assess problem
      solving and planning skills. Clinically, the measure has demonstrated sensitivity
      in discriminating between performance among individuals with varying severity of
      closed head injury (CHI). However, ceiling effects have been demonstrated with
      preadolescent and adolescent CHI samples. An extended version of the Tower of
      London (TOL-E) was devised to minimize these ceiling effects. In this study we
      examined the performance of 26 normal children between the ages of 7 and 16 years
      on the TOL-E. Significant complexity and age effects suggest that the TOL-E
      contributes a significant level of complexity relative to the original TOL across
      all age groups. This finding has implications for the measure's ability to detect
      the development of planning and problem solving in normal children as well as to
      differentiate between impaired and nonimpaired samples.

PMID- 12058834
TI  - The role of early parenting in children's development of executive processes.
AB  - Using structural modeling, we examined the influence of mothers' verbal input
      that provided information about associations between objects and actions
      (scaffolding) at 3 and 4 years of age on children's 6-year executive processing
      skills. Executive processing skills were measured by search retrieval and
      independent goal-directed play tasks. A set of 4-year basic skills (language,
      memory, nonverbal problem solving) considered to be prerequisites for executive
      processing also were included. Patterns of influence across these variables were
      examined for 253 children who varied in neonatal complications and in their
      degree of risk for later developmental problems. Results showed that mothers'
      early verbal scaffolding at 3 years indirectly influenced both types of executive
      processing skills at 6 years by directly influencing children's language and
      nonverbal problem-solving skills at 4 years of age. Four-year scaffolding did not
      show direct influences on later executive processing skills. The provision of
      this form of maternal verbal input when children are rapidly developing language
      appears to support a set of basic skills necessary for later executive
      processing.

PMID- 12058835
TI  - Executive function profile of children with attention deficit hyperactivity
      disorder.
AB  - We explored the neuropsychological profile for executive functions of children
      with attention deficit hyperactivity disorder (ADHD) to assess whether problems
      associated with the two most cited relevant processes--inhibition and attentional
      problems--were the core of any executive function difficulty. A battery of
      executive function tests was administered to 31 children with a clinical
      diagnosis of ADHD and to 33 normal control participants, all aged between 7 and
      12. The executive function battery encompassed a number of tasks, selected
      because each had multiple measures: a sustained attention reaction time task, a
      related vigilance task, an adaptation of the Hayling Sentence Completion Test, an
      adaptation of the Brixton Spatial Rule Attainment Test, a Letter Fluency task, a
      number Stroop task, and an "n-back" working memory task. The overall pattern of
      the results fit well with those obtained in previous studies as far as
      abnormalities of the ADHD group in the domain of inhibitory processes,
      attentional functions, and executive functions. The children with ADHD, although
      performing well on baseline tasks, performed more poorly than the controls on all
      the experimental tasks with one borderline exception: Letter Fluency, where the
      children with ADHD showed a very different pattern than most adult frontal lobe
      subgroups. However, there was no specific impairment on measures of inhibitory
      processes. In addition, strategy generation and use were severely affected in the
      ADHD group. Particular findings fitted well with disorders of a high-level effort
      system and of a monitoring system.

PMID- 12058836
TI  - The disturbing effect of irrelevant information on arithmetic problem solving in
      inattentive children.
AB  - Two studies explored the influence of irrelevant information on the problem
      solving ability of children rated as inattentive by their teachers, on the basis
      of symptoms of attention deficit hyperactivity disorder as defined by the
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American
      Psychiatric Association, 1994). In the first study, 20 inattentive children,
      fourth and fifth graders, and 20 control children matched for IQ, gender, and
      schooling were administered 12-word arithmetic problems. Four problems included
      only essential information necessary for the problem's solution, whereas the
      other problems included irrelevant information, half at the beginning of the
      problem and half at the end. Although the inattentive children were equal to
      control children in their ability to solve problems with essential information,
      they performed more poorly in using appropriate problem-solving procedures when
      problems included irrelevant information, independent of its position. The second
      study compared the influence of numerical and verbal irrelevant information.
      Nineteen inattentive children and 18 control children, selected with similar
      criteria as Study 1, were presented with 12 problems, 6 with irrelevant numerical
      arithmetic information and 6 with irrelevant verbal information. Both kinds of
      information produced a greater number of procedural errors in the inattentive
      group, but differences in calculation errors were less evident. Furthermore,
      inattentive children were more disturbed when the irrelevant information was
      verbal than when it was numerical, suggesting that inattentive children's
      difficulties in problem solving are partially due to an inability to inhibit
      irrelevant information, especially when it conveys a rich semantic knowledge.

PMID- 12058837
TI  - The development of selective inhibitory control across the life span.
AB  - A modification of the stop-signal task was used to investigate the development of
      selective inhibitory control. A group of 317 participants, age 6 to 82 years,
      performed a visual choice reaction time (go) task and attempted to selectively
      inhibit their response to the go task when hearing one of two randomly presented
      tones (1000 Hz, 250 Hz), each presented on 20% of trials. Measures of response
      execution and inhibition were assessed by using reaction times to the go signal
      (GoRT) and stop signal (SSRT), respectively. Results indicated that SSRT gets
      faster with increasing age throughout childhood, with pronounced slowing in older
      adulthood. In addition, strong evidence was obtained for age-related speeding in
      GoRT throughout childhood, with marked slowing throughout adulthood. Subsequent
      hierarchical regression analyses illustrated that the age-related changes in
      selective inhibitory control could not be explained simply by overall slowing or
      speeding of responses. Findings are discussed in regard to the decay and
      maturation of selective inhibitory control across the life span.

PMID- 12058838
TI  - Longitudinal changes in cognitive and adaptive behavior scores in children and
      adolescents with the fragile X mutation or autism.
AB  - Studies of the relationship between the fragile X (FRAXA) mutation and autism
      have been controversial. Although there are differences between the two
      populations, individuals with FRAXA and autism exhibit remarkably similar
      aberrant behavior patterns. We examined comparably aged children and adolescents
      with FRAXA or autism to determine whether longitudinal changes in cognitive
      ability and adaptive behavior were similar in the two groups. We found decreases
      in IQ scores in young children with FRAXA as well as in those with autism.
      Declines in IQ scores were steeper among children with FRAXA. Older children and
      adolescents with autism exhibit stable test-retest scores, whereas older children
      with FRAXA continue to show decreases. Comparable declines in adaptive behavior
      composite scores were observed in both groups, at all ages tested, and across all
      adaptive behavior domains.

PMID- 12058839
TI  - Medical disorders among inpatients with autism in Denmark according to ICD-8: a
      nationwide register-based study.
AB  - Possible associations between autism and specific medical disorders have been
      suggested, and this could be of relevance in the clinical examination and
      treatment of patients and may help to identify factors involved in the etiology
      or pathophysiology of autism. Two population-based Danish registers were used to
      investigate the occurrence of medical disorders in patients with autism according
      to ICD-8 and in a matched control sample. A total of 29 of the 244 patients
      (11.9%) diagnosed with autism had one or more medical disorders. In contrast to
      previous studies, we did not find an increased occurrence of almost any medical
      disorders. A highly significant increased frequency of congenital malformations
      was found, which may indicate abnormalities in embryogenesis in the etiology of
      autism.

PMID- 12058840
TI  - A comparison study of autism spectrum disorder referrals 1997 and 1989.
AB  - A number of overseas studies have indicated an increase in the prevalence of
      Autism Spectrum Disorder (ASD). In the Australian Capital Territory, information
      (number, age, sex, final diagnosis) was gathered on all children referred for
      suspected ASD to Child and Adolescent Mental Health Service during 1997, and the
      findings were compared with those from a similar study in 1989. It was found that
      (1) there was a 200% increase in positive diagnoses of ASD in 1997 despite a 0.5%
      decrease in population, (2) there was a wider age range in the 1997 cohort, (3)
      there was a 26% increase in milder cases in 1997, and (4) the ratio of boys to
      girls decreased from 8:1 in 1989 to 3.5:1 in 1997. These findings are compared
      with those overseas, and questions are raised for further exploration.

PMID- 12058841
TI  - Do children with autism who pass false belief tasks understand the mind as active
      interpreter?
AB  - Interpretive diversity is the term used by Carpendale and Chandler (1996) to
      refer to the fact that two individuals exposed to precisely the same stimulus may
      interpret it in quite different, but equally plausible, ways. An appreciation of
      interpretive diversity is said by Carpendale and Chandler to represent a
      development in understanding that is qualitatively different from that necessary
      to succeed on false belief tasks. A study is reported in which children with
      autism and children with general delay were given a battery of tasks consisting
      of false belief tasks and tasks designed to test for an understanding of
      interpretive diversity. Findings from the present study offer limited support for
      Carpendale and Chandler's claim that tasks which test for an understanding of
      interpretive diversity may be more difficult than false belief tasks. Between
      group differences in the consistency and quality of responses given by
      participants suggest that autistic and delayed children may have differed
      somewhat in their approach to the tasks given.

PMID- 12058842
TI  - Brief report: imitation effects on children with autism.
AB  - Twenty children with autism (mean age, 5 years) were recruited for the study from
      a school for children with autism. The children were randomly assigned to an
      imitation (n = 10) or contingently responsive (n = 10) interaction group based on
      a stratification table for gender and developmental and chronological age. The
      sessions consisted of four phases, with each phase lasting 3 minutes. In the
      first phase, the child walked into a room that was furnished with a sofa, a
      table, chairs, and two sets of identical toys. An adult was in the room sitting
      very still like a statue (first still-face condition). In the second phase, the
      adult either imitated the child or was contingently responsive to the child. In
      the third phase, the adult sat still again (second still-face condition), and in
      the fourth phase, the adult engaged in a spontaneous interaction. During the
      third phase (the second still-face condition), the children in the imitation
      group spent less time in gross motor activity and more time touching the adult,
      as if attempting to initiate an interaction. The contingency condition appeared
      to be a more effective way to facilitate a distal social behavior (attention),
      whereas the imitative condition was a more effective way to facilitate a proximal
      social behavior (touching).

PMID- 12058844
TI  - Our grandson has autism. What do we do?

PMID- 12058843
TI  - A case of N-acetyl galactosaminidase deficiency (Schindler disease) associated
      with autism.

PMID- 12058845
TI  - Looking at images with human figures: comparison between autistic and normal
      children.
AB  - Based on clinical observations of abnormal gaze behavior of autistic children, it
      has been suggested that autistic children have a problem in processing social
      information. Several studies on eye movements have indeed found indications that
      children with autism show particularly abnormal gaze behavior in relation to
      social stimuli. However, the methodology used in such investigations did not
      allow for precise gaze analysis. In the present study, the looking behavior of
      autistic children toward cartoon-like scenes that included a human figure was
      measured quantitatively using an infrared eye-tracking device. Fixation behavior
      of autistic children was similar to that of their age- and IQ-matched normal
      peers. These results do not support the notion that autistic children have a
      specific problem in processing socially loaded visual stimuli. Also, there is no
      indication for an abnormality in gaze behavior in relation to neutral objects. It
      is suggested that the often-reported abnormal use of gaze in everyday life is not
      related to the nature of the visual stimuli but that other factors, like social
      interaction, may play a decisive role.

PMID- 12058846
TI  - The behaviors of parents of children with autism predict the subsequent
      development of their children's communication.
AB  - The present study focused on behaviors that caregivers of children with autism
      show during play interactions, particularly the extent to which the caregiver's
      behavior is synchronized with the child's focus of attention and ongoing
      activity. The study had two major findings. First, caregivers of children with
      autism synchronized their behaviors to their children's attention and activities
      as much as did caregivers of children with developmental delay and caregivers of
      typically developing children, matched on language capacities. Second, caregivers
      of children with autism who showed higher levels of synchronization during
      initial play interactions had children who developed superior joint attention and
      language over a period of 1, 10, and 16 years than did children of caregivers who
      showed lower levels of synchronization initially. These findings suggest a
      developmental link between parental sensitivity and the child's subsequent
      development of communication skills in children with autism. Implications for
      parent training interventions are discussed.

PMID- 12058847
TI  - Interrelations among social-cognitive skills in young children with autism.
AB  - Typically developing infants show a reliable developmental sequence of emergence
      of early social-cognitive skills, such as joint attention, communicative
      gestures, gaze and point following, imitation, and referential language. First
      infants share others' attention, then they follow others' attention and then
      behavior, and then they direct others' attention and then behavior. The current
      study used a series of tests from a study of typically developing infants
      (Carpenter, Nagell, & Tomasello, 1998) to investigate interrelations among these
      social-cognitive skills in young children with autism and children with other
      developmental delays. Tests of object permanence, spatial relations, facial and
      manual imitation, and executive function also were included. We found that for
      most children with autism, unlike other children, tests involving others'
      attention were more difficult than tests involving others' behavior. However,
      within the domains of attention and behavior, the typical pattern of sharing,
      then following, and then directing was evident. There were several positive
      intercorrelations among the social-cognitive skills (as there were for typically
      developing infants), but there also was some evidence of individual differences
      in patterns. Implications for theories of social-cognitive and language
      development are discussed.

PMID- 12058848
TI  - Sleep disturbance in cancer patients.
AB  - Sleep difficulty is a prominent concern of cancer patients, yet there has been no
      large study of the prevalence and nature of sleep disturbance in cancer patients.
      This cross-sectional survey study examined: (a) the prevalence of reported sleep
      problems in patients attending six clinics at a regional cancer centre; (b) sleep
      problem prevalence in relation to cancer treatment; and (c) the nature of
      reported insomnia (type, duration, and associated factors). For three months, all
      patients attending clinics for breast, gastrointestinal, genitourinary,
      gynecologic, lung, and non-melanoma skin cancers were offered a brief sleep
      questionnaire. Response rate was 87%; the final sample size was 982. Mean age of
      respondents was 64.9 years (SD 12.5). The most prevalent problems were excessive
      fatigue (44% of patients), leg restlessness (41%). insomnia (31%), and excessive
      sleepiness (28%). Chi square tests showed significant variation among clinics in
      the prevalence of most sleep problems. The lung clinic had the highest or second
      highest prevalence of problems. The breast clinic had a high prevalence of
      insomnia and fatigue. Recent cancer treatment was associated with excessive
      fatigue and hypersomnolence. Insomnia commonly involved multiple awakenings (76%
      of cases) and duration > or = 6 months (75% of cases). In 48% of cases, insomnia
      onset was reported to occur around the time of cancer diagnosis (falling within
      the period 6 months pre-diagnosis to 18 months post-diagnosis). The most
      frequently identified contributors to insomnia were thoughts, concerns, and
      pain/discomfort. In a multivariate logistic regression analysis, variables
      associated with increased odds of insomnia were fatigue, age (inverse
      relationship), leg restlessness, sedative/hypnotic use, low or variable mood,
      dreams, concerns, and recent cancer surgery. This study provides new information
      about sleep-related phenomena in cancer patients, information which will be
      useful in planning supportive care services for cancer patients.

PMID- 12058849
TI  - Comparing social inequalities in health in Spain: 1987 and 1995/97.
AB  - To evaluate the trend in social inequalities in health in Spain between 1987 and
      1995/97, we carried out a secondary analysis of the Spanish National Interview
      Surveys from 1987, 1995 and 1997. We studied less-than-good perceived general
      health and four chronic conditions--heart disease, diabetes mellitus, chronic
      bronchitis/asthma and allergies--by social class and educational level in men and
      women aged 25-74 years. Among men, the age-adjusted prevalence rate ratio of less
      than-good perceived general health by social class decreased from 1.32 to 1.23
      between 1987 and 1995,97: however, the prevalence rate ratio by educational level
      increased from 1.47 to 1.57. Among women, the prevalence rate ratio of less-than
      good perceived general health increased between the first and second period as
      much by social class from 1.18 to 1.26, as by educational level--from 1.59 to
      1.66. For heart disease the age-adjusted prevalence rate ratio by social class
      among men was 1.12 in 1987 and 0.72 in 1995/97, while the prevalence rate ratio
      by educational level was around I in both periods, among women, the prevalence
      rate ratio for heart disease by social class was the same in 1987 and in 1995/97,
      but the prevalence rate ratio by educational level increased between the first
      and second period. For diabetes mellitus and chronic bronchitis/asthma, the
      prevalence rate ratio increased by social class and educational level between the
      first and second period in both men and women. Finally, the prevalence rate ratio
      for allergies was always < 1, although its magnitude increased between 1987 and
      1995/97. In general, health inequalities were larger by educational level than by
      social class and were larger in women than in men. Inequalities in perceived
      general health, diabetes mellitus and chronic bronchitis/asthma increased in
      Spain between 1987 and 1995/97.

PMID- 12058851
TI  - Meanings of immediate: the practical use of the Patient's Charter in the accident
      and emergency department.
AB  - The publication of the Patient's Charter in Britain enabled patients to have
      access to a series of documented standards relating to health care provision in a
      variety of situations. However since its introduction much discussion has taken
      place as to its application in clinical practice. An initial interest in the
      accomplishment of routine accident and emergency (A& E) nursing work led to the
      identification of issues associated with the use of the Patient's Charter
      standards; particularly those associated with immediate assessment in the A & E
      department. Data were collected from 60 nurses in five A& E departments and
      analysed using a multidisciplinary multistage approach. Findings suggest that
      nurses are expected to juggle the daily tensions produced by the Charter
      standards, associated with initial assessment, alongside the accomplishment of
      other aspects of the work dedicated to the safe movement of patients through the
      system. Tensions are rooted in two particular issues. Firstly, the meanings of
      immediate assessment continue to remain open to interpretation and therefore
      difficult to capture and manage. Secondly, the Patient's Charter standards,
      associated with immediate assessment, deal with one aspect of the work only and
      yet the accomplishment of A & E work is dependent upon maintaining a perception
      of order and shape throughout the whole department. Ultimately both issues have
      an impact on nurses' recognition and management of what they know to be the
      normal appearances and shape of routine work.

PMID- 12058850
TI  - Attitudes to bioethical issues: a case study of a screening project.
AB  - Commonly expressed in theoretical discussions about ethical problems in the
      context of epidemiology and screening is the need for more data. A study was
      carried out involving 21 explorative interviews with participant and
      nonparticipant mothers in a neonatal research screening project in progress in
      Sweden, ABIS (All Babies in Southeast Sweden). The respondents were asked, by way
      of open-ended questions, to give their opinions about certain ethical issues:
      informed consent; reasons for joining/declining; surrogate decision; the
      collection, analysis and storage of written and "live" material (biobanks);
      intervention etc. The ethical implications mentioned in the literature mostly
      concern the risk of creating distress and anxiety (anxiety and possible
      stigmatisation in respect of positive or false-positive results, worry about
      material collected and stored, distress caused by blood sampling procedures,
      etc.). Our results do not support the idea that the risks are substantial. The
      respondents rather indicate an attitude of benevolence--they are positive both to
      the current research on children, to the material they contribute (both written
      material and "biomaterial"), to possible results and intervention plans. On the
      other hand the participants expressed concern about the storage of material and
      the right to be informed of any screening/project results. Further studies in
      this field are needed and would be of help in theoretical discussion, the work of
      ethical committees and the designing of, for example, screening and research
      projects.

PMID- 12058852
TI  - The relevance of client-centered communication to family planning settings in
      developing countries: lessons from the Egyptian experience.
AB  - Concern for client's rights in the provision of reproductive health services in
      the developing world has prompted intense efforts by international experts to
      promote client-centered models of communication as a replacement for more
      provider-centered approaches. Nonetheless, the usefulness or feasibility of cross
      cultural transplantation of client-centered models of communication has not been
      examined. The present study examines the feasibility, acceptability, and
      effectiveness of client-centered models of communication in 31 family planning
      clinics in Egypt. Consultations between 34 physicians and 112 clients requesting
      family planning methods were audio-taped and analyzed for physician communication
      style. Client satisfaction was measured through exit interviews. Method
      continuation was determined through home interviews at 3 and 7 months from the
      index visit. Based on audio-tape analysis, two-thirds of physician consultations
      were characterized as physician-centered and one-third as client-centered. Client
      centered consultations were only one minute longer than physician-centered
      consultations. A client-centered consultation was associated with a three-fold
      increase in the likelihood of client satisfaction and method continuation at 7
      months. A high proportion of solidarity statements (positive talk) by the
      physician was predictive of client satisfaction whereas a high proportion of
      disagreement statements and directive instructions by the physician were
      predictive of method discontinuation. The study findings suggest that in Egypt,
      as in more developed countries, client-centered models of communication are
      likely to produce better client outcomes than provider-centered models, with no
      substantial changes in the structure of services.

PMID- 12058853
TI  - Shared treatment decision making in a collectively funded health care system:
      possible conflicts and some potential solutions.
AB  - In recent years there has been a growth in the advocacy of shared decision making
      (SDM) between clinicians and patients as a way of practicing medicine. Although
      there is a range of perspectives on what SDM means, in essence it refers to
      greater involvement of the individual patient in deliberations about appropriate
      forms of clinical management. The patient's perception of the role of the doctor
      in SDM is crucial: for it to work successfully, the patient needs to be able to
      be confident that the doctor is focused on which treatment will generate the
      greatest benefit for them. However, the doctor also has responsibilities to
      others, in particular to other patients and potential patients within the
      collectively funded health care system. This dual responsibility can create a
      range of dilemmas for the clinician in the context of SDM: Should they inform
      patients about all effective treatments or just those that the health care system
      considers cost-effective? Do they risk losing patients from their books if they
      inform patients about their responsibilities to the health care system? SDM also
      raises questions about the wider principles of the health care system: Are its
      equity principles consistent with SDM? Should patients with a strong preference
      for an effective but non-cost-effective treatment be permitted to pay for it
      privately? This paper describes the nature of the conflicts that are likely to
      emerge if SDM diffuses within collectively funded health care systems, and
      considers a range of policy responses. It argues that the risk of conflict may be
      reduced by making a clear distinction between clinical guidelines (focusing on
      effectiveness) and system guidelines (focusing on cost-effectiveness).

PMID- 12058854
TI  - Life expectancy and mortality differences between migrant groups living in
      Amsterdam, The Netherlands.
AB  - There is an apparent contradiction between the high level of morbidity and the
      low level of mortality observed in certain groups of migrants living in Europe.
      This observation should have some consequences for health policy development and
      the targeting of resources in a city like Amsterdam. In this paper a number of
      hypotheses to explain the low mortality in migrant groups are discussed. An
      analysis is made of mortality in Amsterdam using data from the civil registry as
      to mortality according to age, sex and nationality group of the deceased.
      Standard demographic techniques such as the standardised mortality ratio (SMR)
      and life table analysis were employed. Life table analysis shows that life
      expectancy in Amsterdam is lowest among residents of Dutch descent (73.3 yr for
      males and 79.1 yr for females) and highest among those of Mediterranean origin
      (77.6 yr for males and 86.1 yr for females). This appears to contradict previous
      research based on the SMR, which showed high mortality in migrant groups. To find
      the cause of this contradiction, the SMR and risk ratios by age are studied. The
      conclusion of this paper is that on the basis of life table analysis it appears
      that some immigrant groups living in Amsterdam have a remarkably high life
      expectancy. Since the SMR is sensitive to demographic differences between groups
      compared, questions can be raised about previous studies using the SMR. It has
      been suggested that the high life expectancy in migrant groups is not really
      caused by good health but by 'spurious' phenomena, such as problems in mortality
      registration. However, in view of the available data it seems likely that some
      migrant groups do in fact have high life expectancy, although the morbidity in
      these groups can be quite high. These findings should inform health-related
      policy.

PMID- 12058855
TI  - Concepts of illness causation and attitudes to health care among older people in
      the Republic of Ireland.
AB  - Fifty-one older people (26 of them women) in the Republic of Ireland were
      interviewed using a semi-structured schedule on their health and illness
      experiences at three different time points in their lives; as children, as young
      adults and presently. Of particular interest were their views about the causes of
      heart disease, cancer and tuberculosis and their experiences of the prevailing
      health care system during their lifetime. Participants were recruited by letter
      from a database of respondents to a previous national quantitative survey of
      older people. Of 247 people originally contacted 127 (51%) responded by letter
      and 51 of these took part in the interview study. Data were analysed according to
      principles of content analysis using NUDIST software. Reported ideas about causes
      of illnesses were multicausal. These were categorised as behavioural, biological,
      psychosocial or other explanations. While respondents placed most emphasis on
      behavioural explanations, this was accompanied by more complex views and critical
      questioning of formal health education messages. There was a strong allegiance to
      current biomedical concepts and practices. This appeared to be explained in part
      by reported negative experiences of health care treatments during childhood,
      particularly in hospitals, now perceived to be much improved. Advances in
      biomedicine were discussed with accounts of benefits received or observed by
      participants. An analysis of the history of health services in Ireland suggests
      that some of the attitudes reported reflect the experiences of the respondents as
      a generation rather than as older people per se and hence highlights the impact
      of public policy on people's experiences of and attitudes toward health and
      health care systems.

PMID- 12058856
TI  - A theoretical and empirical analysis of context: neighbourhoods, smoking and
      youth.
AB  - Numerous studies are currently addressing the issue of contextual effects on
      health and disease outcomes. The majority of these studies fall short of
      providing a theoretical basis with which to explain what context is and how it
      affects individual disease outcomes. We propose a theoretical model, entitled
      collective lifestyles, which brings together three concepts from practice theory:
      social structure, social practices and agency. We do so in an attempt to move
      away from both behavioural and structural-functionalist explanations of the
      differential distribution of disease outcomes among areas by including a
      contextualisation of health behaviours that considers their meaning. We test the
      framework using the empirical example of smoking and pre-adolescents in 32
      communities across Quebec, Canada. Social structure is operationalised as
      characteristics and resources; characteristics are the socio-economic aggregate
      characteristics of individuals culled from the 1996 Canadian Census, and
      resources are what regulates and transforms smoking practices. Information about
      social practices was collected in focus groups with pre-adolescents from four of
      the participating communities. Using zero-order and partial correlations we find
      that a portrait of communities emerges. Where there is a high proportion of more
      socio-economically advantaged people, resources tend to be more smoking
      discouraging, with the opposite being true for disadvantaged communities. Upon
      analysis of the focus group material, however, we find that the social practices
      in communities do not necessarily reflect the "objectified" measures of social
      structure. We suggest that a different conceptualisation of accessibility and
      lifestyle in contextual studies may enable us to improve our grasp on how
      differential rates of disease come about in local areas.

PMID- 12058857
TI  - Socio-demographic correlates of psychiatric morbidity among low-income women in
      Aleppo, Syria.
AB  - Interest in mental morbidity as an important component of health is increasing
      worldwide. Women generally suffer more than men from common mental disorders, and
      discrimination against women adds to their mental sufferings. Studies looking
      into the socio-demographic correlates of women's mental morbidity are lacking in
      most Arab countries. In this study we wanted to determine the spread and socio
      demographic correlates of mental distress among low-income women in Aleppo,
      Syria. A sample of 412 women was recruited from 8 randomly selected primary care
      centers in Aleppo. Response rate was 97.2%, mean age of participants 28 + 8.4
      years, where married women constituted 87.9%. A special questionnaire was
      prepared for the study purpose, utilizing the SRQ-20 non-psychotic items and
      questions about background information considered relevant to the mental health
      of women in the studied population. Interviews were conducted in an anonymous one
      to-one fashion. The prevalence of psychiatric distress in our sample was 55.6%.
      Predictors of women's mental health in the logistic regression analysis were;
      physical abuse, women's education, polygamy, residence, age and age of marriage.
      Among these predictors, women's illiteracy, polygamy and physical abuse were the
      strongest determinants of mental distress leading to the worse outcomes. Our data
      show that mental distress is common in the studied population and that it is
      strongly associated with few, possibly modifiable, factors.

PMID- 12058858
TI  - Health risk escalators and the rehabilitation of offenders with learning
      disabilities.
AB  - This paper presents a study of risk management in a hospital within the UK.
      National Health Service which attempts to rehabilitate offenders with learning
      disabilities. Analysis is based on the metaphor of a 'risk escalator'. Health and
      social care systems can be characterised as risk escalators if they possess three
      attributes. Firstly, risk managers should agree the rough ordering of the
      severity of a set of related risks. Secondly, a repertoire of responses which
      provide different trade-offs between autonomy and safety, and which can be
      calibrated against risk severity, should be available. Thirdly, the potential for
      positive and/or negative feedback, which give risk escalators their dynamic
      character, should be identified. Risk escalators may be deliberately designed, or
      may, like the hospital regime discussed in this paper, coalesce from pre-existing
      sub-systems offering different autonomy/safety balances. They may carry service
      users upwards towards greater safety if needed, as in health screening systems,
      or downward towards greater autonomy if justified, for instance in rehabilitation
      systems. Their therapeutic status is contestable. Upward risk escalators can be
      accused of generating positive feedback, with iatrogenic effect. Downward risk
      escalators may be criticised for pushing service users too strongly towards less
      intense interventions, causing neglect. The present case study brings out
      emergent properties of a downward risk escalator, including: organisational
      disruption to system functioning; preferencing of safety over autonomy; active
      and reflexive system management by clients; multiple, organisational risk
      rationalities; and the reification of riskiness as a generic attribute of
      individuals.

PMID- 12058859
TI  - Awareness among community-dwelling elderly of assistive devices for mobility and
      self-care and attitudes towards their use.
AB  - The researchers conducted a survey by personal interview of elderly people (75
      +years) receiving home nursing (N= 117) in Belgium to investigate the extent of
      their awareness and perceptions of the existing supply of assistive devices for
      mobility and selfcare (ADs). A new scale has been developed to measure the
      possession and the awareness of ADs, the Assistive Devices Awareness Scale. The
      researchers identified important gaps regarding the awareness of ADs, despite
      their widespread usefulness and their commercial availability. Even persons with
      specific disabilities were not necessarily aware of the ADs available to assist
      with their particular problems. Nevertheless, the elderly persons presented
      positive attitudes regarding the possibility of using devices as a partial
      substitute for care and advocated participation in financing the purchase of ADs.
      Opinions regarding the effect of using ADs on feelings of loneliness differed
      quite extensively. Most people who were receiving home nursing already possessed
      ADs. These elderly people perceived mainly positive consequences from using the
      ADs they already possessed. Linear forward regression analysis revealed that for
      the elderly clients of home nursing services, the possession of devices is
      correlated with the extent to which there is a growing need for care, people are
      aware of the existing devices and people perceive the consequences of using ADs
      as positive. Implications for future research are discussed.

PMID- 12058860
TI  - Coping styles and locus of control as predictors for psychological adjustment of
      adolescents with a chronic illness.
AB  - This study examines the way coping styles and locus of control contribute to the
      prediction of psychosocial adjustment in adolescents with a chronic illness.
      Psychosocial adjustment of 84 adolescents aged 13-16 years with a chronic illness
      was assessed with measures of social adjustment, global self-esteem and behavior
      problems. Linear regressions were performed with demographic factors (age and
      gender) and stress-processing factors (coping style and locus of control) as
      predictor variables. Results indicated that coping styles were related to most
      aspects of social adjustment. The coping styles 'seeking social support' and
      'confrontation' were important predictors for positive social adjustment; the
      coping style 'depression' was a predictor for poor adjustment, viz, low social
      self-esteem and high social anxiety. Avoidance and locus of control were not
      strongly associated with psychosocial adjustment. Clinical implications of these
      findings were discussed in terms of preventive interventions for adolescents with
      a chronic illness.

PMID- 12058861
TI  - Immunomodulatory and cytoprotective function of atrial natriuretic peptide.
AB  - The atrial natriuretic peptide (ANP) was described as a peptide hormone
      synthesized and secreted by heart atria. It plays an important role in the
      regulation of volume homeostasis; however, the functions of ANP are not
      restricted to cardiovascular effects. The biological profile of ANP is much
      broader than originally thought. This article focuses on the immunomodulatory and
      anti-inflammatory functions of ANP addressing; for example, the influence of ANP
      on macrophage functions. Another important aspect of ANP reviewed here is its
      cytoprotective potential. The beneficial effect of ANP in preventing cell damage
      caused by ischemia and reperfusion warrants special attention. The therapeutic
      potential of ANP in organ preservation could be important for transplantation
      medicine.

PMID- 12058862
TI  - Lymphokine-dependent proliferation of T-lymphoid cells: regulated responsiveness
      and role in vivo.
AB  - The discovery of lymphokines stemmed from their ability to promote T-lymphocyte
      proliferation in vitro. Even after 20 years of intensive investigation, crucial
      aspects remain to be clarified about the role of specific lymphokines in T-cell
      proliferation and the biochemical mechanisms by which they play these roles,
      particularly in vivo. The present review focuses on conventional populations of
      TCR(alpha)beta T cells. Older findings and new insights into the function of
      specific lymphokines in T-lymphocyte proliferation in vivo are summarized along
      with unanswered questions raised by these observations. Vital contributions of
      lymphokines to clonal proliferation arise from two processes: the protection of
      cells against apoptosis and the activation of cell cycling. Findings are
      underscored indicating that the activity of a particular lymphokine depends on
      the subset of T cells (CD4 vs. CD8; naive vs. memory) to which it binds, and that
      point to potential pitfalls of extrapolating from tissue culture-adapted models
      to the regulation of T cells in vivo. After summaries of signaling mechanisms
      related to the proliferative activity of lymphokines, recent findings are
      highlighted suggesting that such signaling is a regulated and plastic process
      rather than one fixed schema of action.

PMID- 12058863
TI  - Neuropeptides and the immune system: focus on dendritic cells.
AB  - Neuropeptides are small, biologically active peptides derived from the central
      and peripheral nervous system. It is increasingly clear that besides their
      function as neurotransmitters, these peptides have an influence on almost all
      body functions including the immune system. Since dendritic cells are the most
      efficient antigen-presenting cells that stimulate naive T cells, thus promoting
      adaptive immunity, it is not surprising that interactions between neuropeptides
      and dendritic cells take place. The current review addresses several aspects of
      dendritic cell-related neuroimmunology and focuses on the role of neuropeptides
      as immunomodulators. Moreover, we present a novel concept of neuropeptide
      mediated regulation of dendritic cell migration. The importance of chemokines in
      immunity is generally accepted. It may be that not enough attention has been paid
      to the possible role of nervous system-derived peptides in regulating immune
      reactions.

PMID- 12058864
TI  - Stresses in mandibular cortical bone during mastication: biomechanical
      considerations using a three-dimensional finite element method.
AB  - This study investigated biomechanical aspects of the action of the biting force
      during mastication upon the mandibular bone in the lower first molar area. A
      three-dimensional (3D) finite element model (FEM) consisting of the tooth,
      periodontal ligament (PDL), alveolar bone, and cortical bone corresponding to the
      lower first molar area based on computed tomogram (CT) images was constructed.
      The model was then analyzed while applying a biting force during mastication,
      which was transmitted from the tooth to the cortical bone, through the PDL and
      cancellous bone. A compressive stress of 0.3-7.9 MPa acted on the cortical bone
      during mastication. In the model, the stress in the cortical bone was distributed
      from the linguo-superior margin to the basal area, and was also observed in the
      bucco-medial area. These areas completely agreed with the areas that were
      significantly thicker in the morphological study described by Masumoto et al.
      (10). It is suggested that there may be a relationship between masticatory force
      and cortical bone hypertrophy. Further study of the effects of various factors is
      required.

PMID- 12058865
TI  - Differential diagnosis between dentigerous cyst and benign tumor with an embedded
      tooth.
AB  - It has been generally recognized that the radiological appearances of cysts and
      tumors related to an embedded tooth are similar. However, based on their clinical
      experience, Abrams et al. pointed out that there was a difference between the two
      lesions at the attachment point to the embedded tooth. To investigate this
      difference, we conducted a study employing the radiographs of patients who
      visited Nihon University Dental Hospital at Matsudo and were pathologically
      defined as having a cyst or tumor. Using radiographs of these patients, we
      investigated the attachment point to the embedded tooth, and expressed the
      results as the proportion of the attachment point to the embedded tooth root
      length. The study was carried out in 100 patients with cysts (87 dentigerous
      cysts and 13 odontogenic keratocysts), and 27 patients with benign tumors (24
      ameloblastomas and three adenomatoid odontogenic tumors). Prior to treatment
      based on the numerical results, the distribution of the results was examined.
      Thus, we evaluated several methods of examining the distributions, and found the
      best method to be discriminant analysis. The results showed that the
      discriminated boundary value (from the cemento-enamel junction) was 0.38 for the
      embedded tooth root length. The cases showing a boundary value of less than 0.4
      for the cemento-enamel junction were judged to be cysts, and those showing a
      value of 0.4 or more were judged to be benign tumors. The rate of misjudgement
      was 28% in the cyst group and 33.3% in the benign tumor group.

PMID- 12058866
TI  - Use of an ultrasonic device for the determination of elastic modulus of dentin.
AB  - The mechanical properties of dentin substrate are one of the important factors in
      determining bond strength of dentin bonding systems. The purpose of this study
      was to determine the elastic modulus of dentin substrate with the use of an
      ultrasonic device. The dentin disks of about 1 mm thickness were obtaining from
      freshly extracted human third molars, and the dentin disk was shaped in a
      rectangular form with a line diamond point. The size and weight of each specimen
      was measured to calculate the density of the specimen. The ultrasonic equipment
      employed in this study was composed of a Pulser-Receiver (Model 5900PR,
      Panametrics), transducers (V155, V156, Panametrics) and an oscilloscope. The
      measured two-way transit time through the dentin disk was divided by two to
      account for the down-and-back travel path, and then multiplied by the velocity of
      sound in the test material. Measuring the longitudinal and share wave sound
      velocity determine elastic modulus. The mean elastic modulus of horizontally
      sectioned specimens was 21.8 GPa and 18.5 GPa for the vertically sectioned
      specimens, and a significant difference was found between the two groups. The
      ultrasonic method used in this study shows considerable promise for determination
      of the elastic modulus of the tooth substrate.

PMID- 12058867
TI  - 1Alpha25(OH)2D3 interferes with retinoic acid-induced inhibition of c-fos gene
      expression for AP-1 formation in osteoblastic cells.
AB  - Our previous studies demonstrated retinoic acid (RA) inhibition of activation
      protein-1 (AP-1) formation in TNF-alpha-treated osteoblastic MC3T3-E1 cells via c
      fos suppression. In the present study, we observed that 1alpha25(OH)2D3 was able
      to interfere at the transcriptional level with RA inhibition of TNF-alpha-induced
      c-fos gene expression in cells when the cells were incubated with the vitamin for
      24 hr before the RA treatment. 22-Oxa-1,25(OH)2D3 (OCT), an analog derivative of
      1alpha25(OH)2D3, having high affinity for the vitamin D3 receptor (VDR), also
      interfered with the RA-induced inhibition of c-fos gene expression in the TNF
      alpha-treated cells. In contrast, this was not the case for 24,25(OH)2D3.
      Moreover, we observed that the interfering effect was clearly blocked by
      pretreatment with VDR antisense oligonucleotide. 1alpha25(OH)2D3 interfered with
      RA inhibition of the TPA-response element binding activity of AP-1 in the
      cytokine-treated cells. Furthermore, 1alpha25(OH)2D3 actually blocked the AP-1
      mediated gene expression of monocyte chemoattractant JE/MCP-1 induced in the
      cytokine-treated cells. The present study suggests a regulatory interference by
      1alpha25(OH)2D3 for RA inhibition of TNF-alpha-induced AP-1 activity in
      osteoblasts.

PMID- 12058868
TI  - Hepatocyte growth factor in saliva: a possible marker for periodontal disease
      status.
AB  - Hepatocyte growth factor (HGF) acts as a mitogen, motogen, morphogen and anti
      apoptotic factor for various kinds of epithelial cells. We previously showed that
      periodontal fibroblasts secreted an HGF-like chemoattractant for a gingival
      epithelial cell line and found that HGF content in gingival crevicular fluid was
      well correlated with probing depth, gingival index, and interleukin-1beta
      concentration. To examine whether HGF in whole (mixed) saliva would be a useful
      marker for periodontal disease status, we investigated the relationship between
      salivary HGF levels and clinical parameters of 65 adults (50 men and 15 women).
      Unstimulated whole (mixed) saliva was collected from each subject and the HGF
      level was determined with an ELISA kit. After sample collection, probing depths
      and bleeding on probing were monitored. Significant correlations were found
      between salivary HGF levels and the number of probing depths exceeding 4 mm (r =
      0.541), the number of probing depths exceeding 6 mm (r = 0.683), the deepest
      probing depth of each subject (r = 0.558) and the percentage of sites positive
      for bleeding on probing (r = 0.511). These results suggest that salivary HGF may
      be a novel marker for periodontal diagnosis in screening tests.

PMID- 12058869
TI  - Effect of commercial ethanol propolis extract on the in vitro growth of Candida
      albicans collected from HIV-seropositive and HIV-seronegative Brazilian patients
      with oral candidiasis.
AB  - The present study assessed the susceptibility of Candida albicans strains,
      collected from HIV-positive patients with oral candidiasis, to a commercial 20%
      ethanol propolis extract (EPE) and compare it to the inhibitory action of the
      standardized antifungal agents nystatin (NYS), clotrimazole (CL), econazole (EC),
      and fluconazole (FL). Twelve C. albicans strains collected from HIV-positive
      patients with oral candidiasis were tested. The inhibition zones were measured
      with a pachimeter and the results are reported as means and standard deviation (M
      +/- SD). Data were analyzed statistically by the non-parametric Kruskal-Wallis
      test. EPE inhibited all the C. albicans strained tested. No significant
      difference was observed between the results obtained with NYS and EPE, while
      significant differences were observed between EPE and other antifungals. The C.
      albicans strains tested showed resistance to the remaining antifungal agents. The
      propolis extract used in this study inhibited the in vitro growth of C. albicans
      collected from HIV-seropositive Brazilian patients, creating/forming inhibition
      zones like those ones formed by NYS. This fact suggests that commercial EPE could
      be an alternative medicine in the treatment of candidiasis from HIV-positive
      patients. However, in vivo studies of the effect of EPE are needed to determine
      its possible effects on the oral mucosa.

PMID- 12058870
TI  - Primary intraosseous carcinoma arising from an odontogenic cyst: a case report
      and review of the Japanese cases.
AB  - A rare case of primary intraosseous carcinoma (PIOC) arising from an odontogenic
      cyst in a 58-year-old man is reported. Clinical and radiological examinations
      revealed an odontogenic cyst of the maxilla. Histopathologically, the lesion was
      composed of a cyst with a parakeratotic epithelial lining and well-differentiated
      squamous cell carcinoma, showing continuity between them without a connection to
      the oral mucosa. Twenty-eight well-documented Japanese cases of Type-1 PIOC,
      including the present case, were reviewed. The mean age of the 28 patients was
      56.1 years, and the male to female ratio was 1.8:1.0. Compared with currently
      reported Japanese reviews of Type-3, foreign Type-1 and Type-3, there were no
      significant differences in mean patient age and sexual predominance, and no
      racial difference. The pathogenesis of Type-1 PIOC is also discussed.

PMID- 12058871
TI  - Primary lingual tuberculosis: a case report with review of literature.
AB  - A case of primary tuberculosis of the tongue, an extremely rare entity is
      presented. The clinical manifestation, diagnosis and the response to
      antituberculous treatment are considered. The literature is also reviewed.

PMID- 12058872
TI  - Solitary neurofibroma of the oral mucosa: a previously undescribed variant of
      neurofibroma.
AB  - We report a distinct morphologic type of neurofibroma, lipomatous neurofibroma,
      arising in the oral mucosa, which has not been described previously in the
      literature. A 25-year-old female patient presented with a solitary mucosal mass
      on the palatal gingiva. Although the limited biopsy material was diagnosed as a
      spindle cell lipoma, characteristic light microscopic neurofibromatous areas,
      intricately admixed with mature fat, were found in the entire resection specimen.
      Immunohistochemically, many of the spindle cells were positive, either diffusely
      or focally, for common neural markers, with patchy staining for CD34 and
      epithelial membrane antigen. S-100 protein was also positive in adipocytes.
      Ultrastructural examination confirmed the diagnosis of neurofibroma and suggested
      an intimate relationship between neoplastic neural cells and adipocytes.

PMID- 12058874
TI  - Rippling muscle syndrome.

PMID- 12058873
TI  - Effects of ipriflavone on bone augmentation within a titanium cap in rabbit
      calvaria.
AB  - Ipriflavone (7-isopropoxyisoflavone, IP), a drug used in the treatment of
      osteoporosis, may promote bone formation during bone remodeling. IP has been
      shown to accelerate both the activity of, and formation of mineralized nodules by
      a human osteosarcoma cell line at an early stage. However, the direct effects of
      IP on bone augmentation have not been investigated. The purpose of this study was
      to determine whether IP induces bone augmentation within a titanium cap in rabbit
      calvaria at an early stage. Five adult male Japanese white rabbits were used. One
      cap (test site) was packed with IP in a collagen gel, and the other (control
      site) was packed with the collagen gel alone. After the one- and three-month
      healing periods, we measured the newly generated tissue and bone within the
      titanium caps. The amount of newly generated tissue within the titanium caps of
      the control sites was higher than the tests sites after one month and three
      months. However, the percentage of newly generated bone/bone marrow in the newly
      generated tissue at the test sites was higher than for the control sites after
      one month and three months. These results suggest that IP affects the quality of
      bone augmentation at an early stage.

PMID- 12058875
TI  - Transverse myelitis in systemic lupus erythematosus.

PMID- 12058876
TI  - Reactive amyloidosis and familial Mediterranean fever (FMF).

PMID- 12058877
TI  - Is type 2 diabetes a risk factor for silent ischemic brain lesion?

PMID- 12058878
TI  - Angioedema and acquired C1 esterase inhibitor deficiency.

PMID- 12058879
TI  - Secondary amyloidosis in patients with rheumatoid arthritis.

PMID- 12058880
TI  - Treatment of acute ischemic stroke: recent progress.
AB  - Intravenous thrombolysis with tissue plasminogen activator is currently the most
      effective treatment of acute ischemic stroke if administerd within 3 hours after
      symptom onset. Intraarterial thrombolysis by prourokinase is the another choise
      if the middle cerebral artery is occluded and within less than 6 hours after
      onset. Although heparin especially a moderate dose is not proved to be effective,
      a randomized, placebo-controlled trial to determine the safety and efficacy of
      argatroban (a selective thrombin inhibitor) in patients with acute ischemic
      stroke was started in USA. Aspirin provides some benefit to patients with acute
      stroke. However, its effect is not fully satisfactory. Although reports of
      numerous trials for neuroprotective drugs have been disappointing, edaravone
      (free radical scavenger) was approved for the treatment of acute ischemic stroke
      in Japan. In the future, thrombolytic and neuroprotective drugs will be used in
      combination.

PMID- 12058881
TI  - Tamoxifen-induced nonalcoholic steatohepatitis in breast cancer patients treated
      with adjuvant tamoxifen.
AB  - OBJECTIVE: The benefits of 5-year tamoxifen administration for patients with
      estrogen receptor-positive breast cancer undoubtedly outweigh the risk of any
      adverse effects. Massive hepatic steatosis is an example of its side effects.
      Here we show risk factors for the development of massive hepatic steatosis and
      describe a representative clinical course of these patients treated with fibrates
      for the first time. METHODS: Computed tomography (CT) numbers of the liver and
      spleen were measured and correlated to body mass index (BMI) and
      pregnanetriol/pregnanediol ratio in urine (P3/P2 ratio). PATIENTS: We enrolled 56
      premenopausal women treated with breast conservation treatment. They received
      oral tamoxifen (40 mg/day for 2 to 3 years) as adjuvant endocrine therapy with
      systemic chemotherapy. RESULTS: Serum estradiol level in 48 of 56 patients
      treated with tamoxifen was less than 10 pg/ml. The ratio of hepatic CT number to
      splenic CT number<0.9 was related to increased BMI (>23.6 kg/sqm) and reduced
      P/P2 ratio (<1). Fibrates are potent enough to improve hepatic steatosis in
      tamoxifen-induced hepatic steatosis. CONCLUSION: P3/P2 ratio<1 was related to
      sufficient blockade of estrogen receptor proven by the development of massive
      hepatic steatosis. Therefore, we propose that tamoxifen is not a mere antagonist
      of estrogen, but it may also suppress estrogen synthesis when estrogen receptor
      is blocked sufficiently. The undetectable level of serum estrogen in tamoxifen
      treated premenopausal women may partially explain why tamoxifen was so effective
      in estrogen receptor-positive early breast cancer.

PMID- 12058882
TI  - Type 2 diabetes is not a risk factor for asymptomatic ischemic brain lesion--the
      Funagata study.
AB  - OBJECTIVE: The purpose of this study is to clarify whether type 2 diabetes (DM)
      is a risk factor for asymptomatic (silent) ischemic brain lesion, which is
      controversial at present. SUBJECTS AND METHODS: The subjects (n=187), who showed
      normal results on both neurological and neuropsychological examinations,
      underwent a 75-g OGTT and were examined by brain MRI on T1-weighted, T2-weighted,
      and FLAIR (fluid-attenuated inversion recovery) images. Their brain MRIs were
      evaluated quantitatively with the ischemia rating scale defined here. The
      subjects were grouped based on their glucose tolerance: normal glucose tolerance
      (NGT) (n=48), impaired glucose tolerance (IGT) (n=62), and DM (n=65). The
      subjects with DM were further divided based on their duration of illness: 20 with
      short duration (short DM: 1.3+0.8 years) and 45 with long duration (long DM;
      8.9+/-5.4 years). Ages were matched among the groups. RESULTS: The percentages of
      individuals with asymptomatic ischemic brain lesion were 81% in NGT, 74% in IGT,
      65% in short DM, and 78% in long DM. No significant difference was observed among
      the groups in terms of the percentage. Namely, even in individuals with a long
      history of DM without clinical stroke, the prevalence of asymptomatic ischemic
      brain lesion was not different from that of the other groups. Multiple regression
      and multiple logistic regression analyses showed that age and hypertension were
      significant independent risk factors for asymptomatic ischemic brain lesion,
      whereas hypercholesterolemia, smoking, and glucose intolerance, including IGT,
      short DM and long DM, were not. CONCLUSION: DM is not a risk factor for
      asymptomatic ischemic brain lesion.

PMID- 12058883
TI  - Variability in cholesteryl ester transfer protein in healthy Japanese hyper-HDL
      cholesterolemic subjects.
AB  - OBJECTIVE: Hyper-high density lipoprotein (HDL)-cholesterolemia has been
      considered to be anti-atherogenic and is referred to as longevity syndrome.
      However, hyper-HDL-cholesterolemia induced by a cholesteryl ester transfer
      protein (CETP) deficiency may not be athero-protective, rather being atherogenic
      in nature. In a rural area in central Japan, the incidence of hyper-HDL
      cholesterolemia has been found to be rather high (3.1% of healthy people). We
      studied healthy Japanese people in this area with hyper-HDL-cholesterolemia,
      particularly in relation to CETP. METHODS: Serum lipids were analyzed, and CETP
      mass was determined with an enzyme immunoassay method. MATERIALS: Blood was drawn
      after an overnight fast from 17 Japanese (5 males and 12 females) with serum HDL
      cholesterol (C) > or =100 mg/dl. RESULTS: Serum CETP mass in hyper-HDL
      cholesterolemic subjects was distributed in a wide range. Serum CETP mass was
      positively correlated with low-density lipoprotein (LDL)-C, apolipoprotein (Apo)
      B, and LDL-C/HDL-C, with statistical significance. CETP was also positively
      correlated with LDL-C/Apo B. CONCLUSION: These results suggest that hyper-HDL
      cholesterolemia may not be a single clinical entity, but a mixture of various
      pathophysiological conditions, and that the ratio of LDL-C to HDL-C and the size
      of LDL may be important factors in classifying these conditions.

PMID- 12058884
TI  - The acute effects of glycemic control on axonal excitability in human diabetic
      nerves.
AB  - OBJECTIVE: To investigate whether glycemic control is associated with reversible
      changes in axonal excitability in human diabetic nerves. It is known that
      voluntary contraction or compression ischemia alters nerve Na+/K+ pump activity,
      and axonal excitability changes due to the pump activity can be estimated by
      threshold tracking. METHODS: Threshold, the current required to produce a
      compound muscle action potential 50% of maximum, was determined from the stimulus
      response curve, and threshold changes produced by maximal voluntary contraction
      or ischemia were measured before and after insulin treatment in 10 diabetic
      patients. RESULTS: Within 3 weeks of the start of treatment, the threshold
      changes became greater following voluntary contractions (+13+/-4% versus +23+/
      5%; mean+/-SEM; p=0.04) and during ischemia (-5+/-2% versus -11+/-2%; p=0.04).
      CONCLUSIONS: The extent of threshold fluctuation depends on multiple metabolic
      factors associated with diabetes such as decreased Na+/K+ ATPase activity,
      increased anaerobic glycolysis, and tissue acidosis, and nerve excitability can
      respond quickly to glycemic control in diabetic patients.

PMID- 12058885
TI  - Experience with oseltamivir in the control of nursing home influenza A outbreak.
AB  - OBJECTIVE: Influenza outbreaks have revealed that elderly persons are a great
      risk of death and serious complications after infection. The administration of
      oseltamivir, a neuramidase inhibitor, is effective for prophylaxis of influenza
      and to reduce disease duration and severity in healthy adults with naturally
      acquired febrile influenza. To clarify the usefulness of oseltamivir in the
      elderly we administered oseltamivir to all residents when an influenza A outbreak
      occurred in a nursing home. PATIENTS: Sixty-eight residents in the nursing home
      were investigated in which the influenza A outbreak occurred; 32 residents had
      fever and 28 residents were positive for influenza A with direct enzyme
      immunoassay. METHODS: Oseltamivir was administered at 75 mg twice daily for 5
      days to all residents. RESULTS: Oseltamivir almost inhibited symptom onset in the
      influenza A-positive afebrile group. Initiation at 0 hour (22 cases), 1-12 hours
      (4 cases), 13-24 hours (5 cases) or 72 hours (1 case) from onset of symptoms was
      associated with mean fever durations of 26+/-18 hours, 38+/-21 hours, 54+/-12
      hours and 120 hours, respectively, indicating that earlier initiation of therapy
      was associated with faster resolution of fever in elderly patients. Oseltamivir
      may be effective for household prophylaxis in the elderly persons. Oseltamivir
      administration was well tolerated in elderly persons. CONCLUSION: Oseltamivir is
      effective for the reduction or prophylaxis of influenza A infection in elderly
      persons.

PMID- 12058887
TI  - Primary hyperparathyroidism with duodenal ulcer and H. pylori infection.
AB  - A patient with duodenal ulcer and primary hyperparathyroidism was found to have
      an abnormally high intragastric pH. The pH level returned to normal after
      surgical removal of the parathyroid adenoma followed by normalization of
      parathyroid hormone (PTH) and serum calcium concentrations. The patient was
      positive for Helicobacter pylon (H. pylori) infection. Although the exact
      mechanism by which chronic hypercalcemia or high PTH level inhibited gastric acid
      secretion in this case remains unclear, our findings suggest that hypercalcemia
      may play some role in H. pylori associated gastroduodenal diseases through
      induction of proinflammatory cytokines or by enhancing the attachment of H.
      pylori to gastric epithelial cells.

PMID- 12058886
TI  - PTHrP-producing tumor: squamous cell carcinoma of the liver accompanied by
      humoral hypercalcemia of malignancy, increased IL-6 and leukocytosis.
AB  - A 77-year-old man was admitted to our hospital showing symptoms of general
      fatigue and appetite loss. He had leukocytosis, thrombocytosis and hypercalcemia
      with elevated serum levels of parathyroid hormone related peptide (PTHrP) and
      interleukin-6 (IL-6). An increase in tumor markers SCC and CYFURA21-1 was
      observed. The liver contained a huge tumor, which was proved to be PTHrP
      producing squamous cell carcinoma by immuno-histochemical analysis. Since the
      tumor did not express IL-6, it was assumed to be induced by PTHrP in osteoblasts.
      This is the first report of PTHrP producing squamous cell carcinoma of the liver.

PMID- 12058888
TI  - Usefulness of the modified lavage technique of Bingisser and KL-6 monitoring in a
      patient with pulmonary alveolar proteinosis.
AB  - A 48-year-old man diagnosed as pulmonary alveolar proteinosis (PAP) received a
      whole-lung lavage by the conventional lavage technique, but he failed to show any
      clinical or functional improvement. Therefore, we applied a modified lavage
      technique of Bingisser resulting in the impressive clinical and functional
      improvement. We measured the levels of KL-6 in bronchoalveolar lavage fluid
      (BALF) at selected time intervals. KL-6 levels in BALF were higher during the
      lavage by the modified lavage technique of Bingisser than the conventional lavage
      technique. We were able to verify the usefulness of the modified lavage technique
      of Bingisser by monitoring the levels of KL-6 in BALF. The modified lavage
      technique of Bingisser may be useful for PAP treatment.

PMID- 12058889
TI  - Amyloid a protein amyloidosis in a patient with plasma cell dyscrasia.
AB  - We report a 59-year-old man who was found to have plasma cell dyscrasia and
      amyloid A protein (AA) amyloidosis during the follow-up period of chronic
      inactive hepatitis C. Clinical manifestations such as swallowing disturbance,
      proteinuria and leg edema were associated with AA amyloid deposits in his tongue
      and kidneys. Although the relationship between these two diseases remains to be
      determined, the ability of peripheral blood mononuclear cells to degradate serum
      amyloid A protein was apparently reduced in this patient, compared with normal
      volunteers. This would, in part, account for the AA amyloid deposition in this
      patient.

PMID- 12058890
TI  - Acute urinary retention as an unusual manifestation of aseptic meningitis.
AB  - A formerly healthy 32-year-old woman was hospitalized for a closer examination of
      undiagnosed fever with mild headache. Despite lack of distinct findings on
      physical and laboratory examinations at admission, she suddenly developed
      anuresis due to acontractile neurogenic bladder. On the basis of her symptoms and
      the faint nuchal rigidity revealed later, as well as the results of cerebrospinal
      fluid analyses, a diagnosis of aseptic meningitis was eventually reached. While
      aseptic meningitis subsided within 3 weeks, about 10 weeks, including a 26-day
      period of anuria, was necessary for complete restoration of normal voiding
      function, necessitating intermittent self-catheterization. Acute urinary
      retention should be considered an uncommon but critical manifestation of aseptic
      meningitis.

PMID- 12058891
TI  - An autopsy case of amyotrophic lateral sclerosis accompanied by syndrome of
      inappropriate secretion of antidiuretic hormone.
AB  - We report an autopsy-confirmed case of amyotrophic lateral sclerosis (ALS)
      accompanied by syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH). A 67-year-old man was admitted to our hospital with muscle weakness,
      dysarthria and dysphagia. During hospitalization, respiratory insufficiency was
      ingravescent, and hyponatremia, hypo-osmolarity, elevated osmotic pressure of
      urine, and elevated urinary sodium excretion were noted. Based on these findings
      we diagnosed ALS with SIADH, and treatment with infusion of concentrated NaCl was
      started. However, the patient died of respiratory failure on day 50. We assumed
      that severely restrictive ventilatory impairment was the cause of SIADH in this
      case.

PMID- 12058892
TI  - Autoimmune acquired form of angioedema that responded to danazol therapy.
AB  - A 51-year-old man with recurrent episodes of angioedema was diagnosed as having
      autoimmune acquired angioedema, based on adult onset, lack of apparent family
      history, decreased activity of C1 esterase inhibitor (C1 INH) and CH50, decreased
      levels of serum C4 and Clq and the presence of autoantibodies to C1 INH. The
      danazol treatment relieved the symptoms of angioedema and increased the C1 INH
      activity and concentration with the normalization of CH50, C1q and C4 levels. To
      our knowledge, this is the first case of autoimmune acquired angioedema in Japan.

PMID- 12058894
TI  - Successful diagnosis using scab for PCR specimen in Tsutsugamushi disease.
AB  - We treated a case of Tsutsugamushi disease diagnosed by polymerase chain reaction
      (PCR) using a scab specimen at the bite site of trombiculid mites. Otherwise the
      diagnosis could not be confirmed by serum antibody test nor the PCR test of
      blood. The genome of Rickettsia tsutsugamushi was detected and identified as the
      Kawasaki serotype strain. An attempt to extract the genome from the scab has not
      been reported, thus our data suggest that the scab is a useful specimen to
      confirm the diagnosis of Tsutsugamushi disease.

PMID- 12058893
TI  - Long-term follow-up of systemic reactive AA amyloidosis secondary to rheumatoid
      arthritis: successful treatment with intermediate-dose corticosteroid.
AB  - Reactive AA amyloidosis frequently develops in patients with a long history of
      rheumatoid arthritis (RA), usually resulting in an unfavorable outcome due to
      dysfunction of the vital organs. We report a 56-year-old woman with this form of
      amyloidosis secondary to RA who has been successfully treated with intermediate
      dose prednisolone for two and a half years since diagnosis. Because prednisolone
      is superior to other drugs used for amyloidosis with respect to possible harmful
      effects on vital organs, we can safely try this drug as an alternative therapy to
      improve the prognosis even in patients with severe organ dysfunction.

PMID- 12058895
TI  - Intrapericardial infusion of urokinase for the treatment of purulent
      pericarditis.

PMID- 12058896
TI  - Purification of the specific immunoglobulin G1 by immobilized metal ion affinity
      chromatography using nickel complexes of chelating porous and nonporous polymeric
      sorbents based on poly(methacrylic esters). Effect of polymer structure.
AB  - Ni2+ complexes of the chelating nonporous and porous bead sorbents based on
      methacrylic esters crosslinked with ethylene dimethacrylate were used in
      isolation of the horseradish peroxidase-specific immunoglobulin IgG1 from the
      crude mouse ascitic fluid by immobilized metal ion affinity chromatography
      (IMAC). Iminodiacetic and aspartic acids were attached to porous poly(glycidyl
      methacrylate) beads differing in size, morphology and chemical composition.
      Ethylenediaminetriacetic acid and quinolin-8-ol chelating groups were attached
      mainly to the surface hydroxyl groups in nonporous poly(diethylene glycol
      methacrylate) beads through spacers. The latter sorbents exhibited better kinetic
      characteristics than the former but a very low IgG1 sorption capacity. In a
      single-step IMAC procedure, the best efficiency in the specific IgG1 purification
      was obtained with porous sorbents (recovery 92%, purity 73%). Differences in IMAC
      separations are discussed from the point of view of morphology of polymer beads
      as well as of the type and concentration of chelating ligands.

PMID- 12058897
TI  - Stationary phase effects on the dynamic affinity of low-molecular-mass
      displacers.
AB  - In this paper, the selectivity of a variety of cation-exchange stationary phases
      was investigated using a homologous series of displacer molecules based on
      pentaerythritol. These displacers were derived from pentaerythritol and contained
      either four trimethyl ammonium groups [pentaerythrityl-(trimethylammonium
      chloride)4, PE(TMA)4], benzene rings [pentaerythrityl-(benzyl dimethylammonium
      chloride)4, PE(DMABzCl)4], heptyl groups [pentaerythrityl-(heptyl
      dimethylammonium iodide)4, PE(DMAHepI)4] or cyclohexyl groups [pentaerythrityl
      (cyclohexyl dimethylammonium iodide)4, PE(DMACyI)4]. This series enabled us to
      probe the secondary interactions that can play a role in the affinity of low
      molecular-mass displacers for different stationary phases. The relative
      affinities of these displacers were examined using a displacer ranking plot based
      on the steric mass action (SMA) isotherm model. While hydrophobicity and
      aromaticity played important roles in generating the affinity to the
      hydrophilized polystyrene-divinylbenzene (Source 15S) and polymethacrylate-based
      (Toyopearl 650M) resins, these secondary interactions had a minimal impact on the
      selectivity in agarose resins coated with dextran (SP Sepharose XL), "gel in a
      shell" (S Ceramic HyperD F), and monolithic (Bio-Rad Uno S6) cation-exchange
      materials. Further, the results with a tentacular stationary phase (Fractogel
      EMD) suggest that the alkyl chains on PE(DMAHepI)4 play an important role in
      increasing the affinity, possibly because of strong interactions between the
      alkyl moiety and the polymer matrix as well as between the charged groups and the
      polyelectrolyte tentacles. The results of this study provide insight into the
      design of high affinity, low-molecular-mass displacers for different cation
      exchange stationary phase materials.

PMID- 12058898
TI  - Galactosyl-biomimetic dye-ligands for the purification of Dactylium dendroides
      galactose oxidase.
AB  - Two anthraquinone galactosyl-biomimetic dye-ligands comprising, as terminal
      biomimetic moiety, galactose analogues (1-amino-1-deoxy-beta-D-galactose and D(+)
      galactosamine) were designed for the enzyme galactose oxidase (GAO), using
      molecular modelling, synthesized and characterized. The biomimetic ligands were
      immobilized on agarose beads and the affinity adsorbents, together with a non
      biomimetic adsorbent bearing Cibacron Blue 3GA, were studied for their ability to
      purify GAO from Dactylium dendroides. Both biomimetic adsorbents showed higher
      purifying ability for GAO compared to the non-biomimetic adsorbent, thus
      demonstrating their superior effectiveness as affinity chromatography materials.
      In particular, the affinity adsorbent comprising, as terminal biomimetic moiety,
      1-amino-1-deoxy-beta-D-galactose (BM1) exhibited the highest purifying ability
      for GAO. This affinity adsorbent did not bind galactose dehydrogenase, glucose
      dehydrogenase, alcohol dehydrogenase, or glucose oxidase. The dissociation
      constant (K(D)) of the immobilized BM1 ligand with GAO was found to be equal to
      45.8 microM, whereas the binding capacity was equal to 709 U per ml adsorbent.
      Therefore, the BMI adsorbent was integrated in a facile two-step purification
      procedure for GAO. The purified enzyme showed a specific activity equal to 2038
      U/mg, the highest reported so far, approximately 74% overall recovery and a
      single band after sodium dodecylsulfate-polyacrylamide gel electrophoresis
      analysis.

PMID- 12058899
TI  - Confocal Raman and fluorescence spectroscopy applied to polymeric chromatographic
      adsorbent particles.
AB  - Distributions of functional groups in individual chromatographic adsorbent
      particles have been investigated using confocal Raman and fluorescence
      spectroscopy. Measurements have been performed with different microscope
      objectives and it was found that an immersion objective should be used when wet
      adsorbent particles are analysed. Nd3+ ions have been used as fluorescence probes
      to evaluate the distribution of chelating and negatively charged functional
      groups. The fluorescence spectrum from Nd3+ has also been used to obtain
      information about the coordination of Nd3+ within the adsorbent particles.

PMID- 12058900
TI  - Prediction of internal standards in reversed-phase liquid chromatography. II.
      Selectivity optimization and internal standard prediction for the quantitation of
      estradiol and levonorgestrel in a transdermal drug delivery formulation based on
      the linear solvation energy relationships.
AB  - This paper describes the results of selectivity optimization and internal
      standard prediction for the quantitation of estradiol and levonorgestrel in
      transdermal patches by reversed-phase liquid chromatography (RPLC) based on the
      linear solvation energy relationships (LSERs). The patch samples are prepared by
      swelling with acetonitrile (ACN) and the separation is performed by Zorbax
      Eclipse XDB ODS columns. A proper retention range is first determined with a
      binary mobile phase of ACN and water based on the general resolution equation.
      The interference to estradiol from a levonorgestrel impurity is then eliminated
      by a ternary mobile phase of acetonitrile-methanol-water with a composition
      predicted by LSERs. When the resolution is optimized and the "open window" in the
      chromatogram for an internal standard is selected, LSERs are used to predict the
      candidate compounds to be evaluated as the internal standard. The approach
      described in this study can be used, in general, to considerably improve the
      efficiency of RPLC method development, particularly for neutral samples. Finally,
      the LSER approach for the selectivity optimization is compared with a statistical
      response surface methodology (RSM) based on a central composite design (CCD) in
      terms of the effectiveness and number of experiments. It is concluded that,
      although the predicted mobile phase composition to achieve the desired
      selectivity is about the same, the LSER approach is more efficient and fewer
      experiments are required.

PMID- 12058901
TI  - Determination of acaricides in honey by high-performance liquid chromatography
      with photodiode array detection.
AB  - Rapid analytical methods are described to control quality of honeys, concerning
      residues of acaricides applied in hives to prevent Varroa jacobsoni infestation.
      A liquid-liquid extraction with hexane-propanol-2-ammonia (60 ml:30 ml:0.28%) was
      used for the simultaneous analysis of coumaphos, bromopropylate, amitraz and
      fluvalinate. For thymol, one clean up on a solid-phase extraction C18 (500 mg, 6
      ml) column was performed; for rotenone, a liquid extraction with dichloromethane
      was realised. Quantitative recoveries obtained with honey were satisfactory and
      were superior to 80%. All acaricides are identified by reversed-phase high
      performance liquid chromatography with photodiode array detection. Quantification
      limits obtained were below maximal residue limits when these exist.

PMID- 12058902
TI  - Temperature effects on the retention of n-alkanes and arenes in helium-squalane
      gas-liquid chromatography. Experiment and molecular simulation.
AB  - Experiments and molecular simulations were carried out to study temperature
      effects (in the range of 323 to 383 K) on the absolute and relative retention of
      n-hexane, n-heptane, n-octane, benzene, toluene and the three xylene isomers in
      gas-liquid chromatography. Helium and squalane were used as the carrier gas and
      retentive phase, respectively. Both the experiments and the simulations show a
      markedly different temperature dependence of the retention for the n-alkanes
      compared to the arenes. For example, over the 60 K temperature range studied, the
      Kovats retention index of benzene is found to increase by about 16 or 18+/-10
      retention index units determined from the experiments or simulations,
      respectively. For toluene and the xylenes, the experimentally measured increases
      are similar in magnitude and range from 14 to 17 retention index units for m
      xylene to o-xylene. The molecular simulation data provide an independent method
      of obtaining the transfer enthalpies and entropies. The change in retention
      indices is shown to be the result of the larger entropic penalty and the larger
      heat capacity for the transfer of the alkane molecules.

PMID- 12058903
TI  - Time-weighted average sampling of airborne n-valeraldehyde by a solid-phase
      microextration device.
AB  - A solid-phase microextraction (SPME) device was used as a time-weighted average
      sampler for n-valeraldehyde. The SPME device was first modified to improve the
      wearer's acceptance as a passive sampler. Then a poly(dimethylsiloxane)
      divinylbenzene fiber was used and O-2,3,4,5,6-(pentafluorobenzyl)hydroxylamine
      hydrochloride (PFBHA) was loaded onto the fiber. Vapors of known concentrations
      around the threshold limit values time-weighted average of n-valeraldehyde and
      specific relative humidities (RHs) were generated by syringe pumps in a dynamic
      generation system. n-Valeraldehyde vapors in gas bags were also generated. An
      exposure chamber was designed to allow measurement of face velocities,
      temperatures, exposing vapor concentrations, and RHs. Gas chromatography with
      flame ionization detection was used for sample analysis. The appropriate
      adsorption time for SPME coating PFBHA was determined to be 2 min and the
      desorption time for oxime formed after sampling was optimized to be 2 min. The
      experimental sampling constant was found to be (3.86+/-0.13) x 10(-2) cm3/min and
      face velocity was not expect to have effect on the sampler.

PMID- 12058904
TI  - Artifact formation due to ethyl thio-incorporation into silylated steroid
      structures as determined in doping analysis.
AB  - Trimethylsilylation of target substances in a mixture of N-methyl-N
      trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide and ethanethiol is
      frequently applied for the application of gas chromatography-mass spectrometry
      (GC-MS) in steroid analysis. However, artifacts were formed when using this
      mixture to silylate the steroids androsterone and etiocholanolone obtained from a
      urine matrix. The artifacts were identified as ethyl thio-containing products of
      the respective trimethylsilyl derivatives. The conversion of the studied products
      increased slowly as a function of time, was dependent on the presence of the
      urine matrix and was significantly accelerated by adding diethyl disulfide to the
      reagent before incubation. Also ethyl thio-incorporation into testosterone and
      epitestosterone was established. A mechanism for ethyl thio-incorporation is
      proposed. The conversion achieved after 120-h sample storage at room temperature
      was insufficient to significantly influence the analysis of androsterone and
      etiocholanolone under the studied conditions. However, the results provide
      fundamental insight into the mechanism of silylation and the occurring side
      reactions. Moreover, when investigating the formation of new metabolites, the
      ethyl thio-incorporation can lead to misinterpretation.

PMID- 12058905
TI  - Extraction of thymol, eucalyptol, menthol, and camphor residues from honey and
      beeswax. Determination by gas chromatography with flame ionization detection.
AB  - A gas chromatographic method to determine thymol, eucalyptol (cineole), menthol
      and camphor residues in honey and beeswax is proposed. To isolate the compounds,
      three methods involving liquid-liquid extraction with methylene chloride,
      distillation, or solid-phase extraction on octadecylsilica cartridges can be
      used. The GC separation is carried out on a 60 m x 0.53 mm Stabilwax DA capillary
      column, using a flame ionization detector. The method is applied to the analysis
      of natural honey and also honey and beeswax samples from beehives treated with
      the above compounds.

PMID- 12058906
TI  - Selective stationary phase for solid-phase microextraction analysis of sarin
      (GB).
AB  - A number of critical field applications require monitoring air samples for trace
      levels of chemical warfare agents. Solid-phase microextraction (SPME) is a
      convenient format to conduct these analyses. Measurements could be significantly
      improved if a SPME phase selective for nerve agents were substituted for non
      selective polymers typically used (e.g., polydimethylsiloxane). This paper
      evaluates a novel stationary phase, previously developed for methylphosphonate
      sensor applications, for use with SPME sampling. The phenol-based polymer, BSP3,
      was found to offer far higher selectivity toward sarin (GB) than
      polydimethylsiloxane due to a pronounced affinity toward the target analyte and a
      lower affinity toward hydrocarbons.

PMID- 12058907
TI  - Gas chromatographic-mass spectrometric separation and identification of
      combustion products of organo-phosphorus and chlorine pesticides and evaluation
      of their impact on the environment.
AB  - A simple and rapid GC-MS method for separation, identification and quantitative
      determination of combustion products of organophosphorus and chlorine pesticides
      viz; monocrotophos, chloropyriphos, butachlor and benzenehexachloride has been
      developed. The method provides a positive means of identifying organic combustion
      products and enables to assess not only their toxicity to human beings but also
      their impact on the environment. The data is useful for emergency preparations in
      case of fire in chemical plants and warehouses that store pesticides in large
      quantities.

PMID- 12058908
TI  - Sensitive method for the detection of 22 benzodiazepines by gas chromatography
      ion trap tandem mass spectrometry.
AB  - A gas chromatography-ion trap tandem mass spectrometry method for simultaneous
      detection of 22 benzodiazepines is presented. Four operating modes were first
      optimized: the electron impact ionization and chemical ionization modes were
      compared on both underivatized and trimethylsilylated drugs. Results were
      compared in terms of sensitivity in MS-MS experiments. The trimethylsilylation of
      benzodiazepines including a protic functional group allows decreasing their
      detection threshold by a factor of 10-100. In terms of sensitivity, the
      comparison between both ionization modes shows that the most efficient one
      depends on the benzodiazepine considered. The use of an ion trap analyzer allows
      switching from an ionization mode to another one during the chromatographic
      process. It also provides a great selectivity owing to the MS-MS and multiple
      reaction monitoring acquisition modes. The detection thresholds are in the range
      10-500 pg/microl for all the studied benzodiazepines but the three "triazolo"
      ones: estazolam, alprazolam and triazolam, have a detection threshold of 1
      ng/microl. The applicability of the method on whole blood and urine extracts was
      demonstrated on an example implying five benzodiazepines among the most
      frequently encountered in forensic toxicology: nordazepam, oxazepam, bromazepam,
      flunitrazepam and prazepam.

PMID- 12058909
TI  - Metal complex-substituted polysiloxanes as novel coatings for capillary
      electrophoresis and capillary electrochromatography.
AB  - Two novel polysiloxane-based polymers, which contain metal complexes, have been
      prepared. To prepare the Co(TACN)3+(2) (TACN= 1,4,7-triazacyclononane) based
      polymers, an orthoamide derivative of TACN was added to bromobutane-substituted
      methylpolysiloxane and hydrolyzed with base. Co(II) was then coordinated to the
      TACN, followed by cobalt oxidation to make polymer A or followed by N-octyl TACN
      coordination and cobalt oxidation to make polymer B. In both materials, TACN
      forms thermodynamically and kinetically stable Co(TACN)3+(2) complexes in which
      the six coordination sites of the Co(III) are occupied by nitrogens from the
      TACN. The polymers were coated on fused-silica capillary columns and spherical
      silica particles, which were used for capillary electrophoresis and capillary
      electrochromatography, respectively. The open and packed columns showed strong
      and pH-independent reversed electroosmotic flow.

PMID- 12058910
TI  - Estimation of sialic acid in a sialoglycan and a sialoglycoprotein by capillary
      electrophoresis with in-capillary sialidase digestion.
AB  - An example of application of in-capillary derivatization for CE, obtained by
      using the throughout-capillary format, is presented. Introduction of a
      sialoglycan (N-acetylneuraminyllactose) or a sialoglycoprotein (bovine serum
      fetuin) sample to a running buffer (pH 5.0) containing N-acetylneuraminidase
      followed by application of a voltage resulted in the release of N
      acetylneuraminic acid (NANA) which could be estimated by CE with UV detection.
      Two-step application of voltages (5 and 20 kV) was proved to be more effective
      for rapid estimation of the released NANA. This format (modified throughout
      capillary format) allowed differential estimation of the NANA present in the
      sample as an impurity and the NANA released from the substrate at the picomol
      level, and thereby reliable micro assay of the sialidase activity. It also
      allowed estimation of the rate constant of this enzymatic reaction.

PMID- 12058911
TI  - Determination of purine and pyrimidine bases in DNA by micellar electrokinetic
      capillary chromatography with electrochemical detection.
AB  - A method based on micellar electrokinetic capillary chromatography with
      electrochemical detection was developed for the determination of cytosine, 5
      methylcytosine (5-MC), thymine, adenine, and guanine in the hydrolysates of DNA.
      The working electrode was fabricated in a novel self-positioning carbon disc
      electrode system that can align the capillary outlet with the working electrode
      without a three-dimensional micromanipulator. The five analytes could be well
      separated within 10 min in a 40 cm length capillary at a separation voltage of 9
      kV in a 40 mmol/l borate buffer (pH 10.0) containing 100 mmol/l sodium dodecyl
      sulfate. Good linearity was observed between peak current and concentration of
      bases over three orders of magnitude with the detection limits (SIN=3) ranging
      from 1.28 x 10(-6) to 5.02 x 10(-6) mol/l. This proposed method demonstrated long
      term stability and reproducibility with relative standard deviations of less than
      5% for both migration time and peak current (n=7). It has been successfully
      applied to determine bases including 5-MC in the hydrolysates of fish sperm DNA,
      calf thymus DNA, and DNA isolated from spleen cells of female mice.

PMID- 12058912
TI  - Convection-aided collection of metal ions using chelating porous flat-sheet
      membranes.
AB  - Chelating porous membranes were prepared by radiation-induced graft
      polymerization of an epoxy-group-containing monomer onto a polyethylene flat
      sheet and subsequent conversion of the epoxy group to an iminodiacetate group as
      a chelate-forming group. The chelating group density on the resultant porous flat
      sheet membrane of 1.0 mol/kg was comparable to that of commercially available
      chelating beads. The pure water permeability of the membrane was 40% that of the
      trunk porous membrane, which was used for microfiltration. During the permeation
      of a copper chloride solution through the membrane, diffusional mass-transfer
      resistance of copper ion was negligible, since the ion was transported by
      convective flow through the pore. The tensile strength and elongation at break of
      the membranes were measured as a function of dose of electron-beam irradiation,
      the degree of grafting, and the chelating group density to determine an
      applicable range for practical use.

PMID- 12058914
TI  - Determination of khellin and visnagin in Ammi visnaga fruits by capillary
      electrophoresis.
AB  - A new, simple and rapid capillary electrophoresis method was developed for the
      identification and quantitative determination of two medically active
      constituents-khellin and visnagin-in the extracts of Ammi visnaga fruits.
      Micellar electrochromatographic separation of khellin and visnagin was carried
      out using 10 mmol/l borate, 50 mmol/l sodium dodecylsulfate, 25% (v/v)
      acetonitrile at pH 9 as running buffer. Ammi visnaga fruits were extracted with
      methanol and the extracts were directly injected without any purification and pre
      separation processes. Coumarin was used as internal standard for quantitation and
      the limits of detection for khellin and visnagin were 2.36 and 1.97 microg/ml,
      respectively using UV detection at 245 nm.

PMID- 12058913
TI  - Utilisation of reversed-phase high-performance liquid chromatography as an
      alternative to silver-ion chromatography for the separation of cis- and trans
      C18:1 fatty acid isomers.
AB  - Silver ion-high-performance liquid chromatography (HPLC) has been commonly used
      for the separation and the analysis of trans-18:1 isomers in partially
      hydrogenated oils and milk fat. This paper describes an easy HPLC method using
      two reversed-phase columns. The cis- and trans-18:1 fatty acids isomers as methyl
      esters were eluted as two separate fractions. The collected fractions were
      analysed by gas chromatography (GC). The purity of the two fractions were tested
      by GC-MS and GC-Fourier transform IR.

PMID- 12058915
TI  - Initial study of using a laminar fluid diffusion interface for sample preparation
      in high-performance liquid chromatography.
AB  - This report describes a new microfluidic device called the H Filter for sample
      preparation prior to HPLC. The H Filters make possible a diffusional transfer of
      an analyte from a sample stream into a stream of a "receiver" fluid. Existing
      mathematical models can be used for optimizing experimental conditions. The
      authors have selected the extraction of the antibiotic cephradine from blood to
      demonstrate the utility of the new device. The extracts of blood samples spiked
      with cephradine levels between 0.2 and 100 microg/ml were analyzed using a C8
      reversed-phase column and UV detection at 260 nm. The HPLC results were in good
      agreement with theory. The recovery of 32.2+/-2.8% was uniform over the entire
      range of cephradine concentrations. The new method completely avoids the use of
      centrifuges, that is otherwise typical for most current methodologies for the
      preparation of blood samples prior to HPLC analysis.

PMID- 12058916
TI  - New sample preparation technique for the determination of avoparcin in
      pressurized hot water extracts from kidney samples.
AB  - A new approach is presented for the determination of avoparcin in tissue.
      Complete recovery from spiked swine kidney was achieved with hot water modified
      with 30% ethanol (v/v). The samples were extracted at 75 degrees C and 50 atm by
      accelerated solvent extraction. In situ sample clean-up was achieved by using
      matrix solid-phase dispersion utilizing the acrylic polymer XAD-7 HP, and by
      adding triethylammonium phosphate (TEAP) to the extraction solvent. The aqueous
      extracts were concentrated by solid-phase extraction (SPE) on the hydrophilic
      interaction chromatography (HILIC) material polyhydroxyethyl aspartamide.
      Complete analyte retention was possible during SPE when the kidney extracts were
      modified with 70% ethanol. A 200 A, 5 microm HILIC column with UV225 detection
      was used for the separation of avoparcin. The retention time was less than 15 min
      with 47% aqueous component in acetonitrile and 15 mM TEAP as eluent. The average
      recovery of avoparcin from kidney samples was 108%.

PMID- 12058917
TI  - Monolithic stationary phases for liquid chromatography and capillary
      electrochromatography.
AB  - A monolithic stationary phase is the continuous unitary porous structure prepared
      by in situ polymerization or consolidation inside the column tubing and, if
      necessary, the surface is functionalized to convert it into a sorbent with the
      desired chromatographic binding properties [J. Chromatogr. A 855 (1999) 273].
      Monolithic stationary phases have attracted considerable attention in liquid
      chromatography and capillary electrochromatography in recent years due to their
      simple preparation procedure, unique properties and excellent performance,
      especially for separation of biopolymers. This review summarizes the preparation,
      characterization and applications of the monolithic stationary phases. In
      addition, the disadvantages and limitations of the monolithic stationary phases
      are also briefly discussed.

PMID- 12058918
TI  - Headspace solid-phase microextraction of higher fatty acid ethyl esters in white
      rum aroma.
AB  - Fatty acid ethyl esters are the main components of rum aroma and play an
      important sensorial impact in these distilled alcoholic beverages. Herein, a
      method for analysing these volatile compounds is described. It involves a
      separation and concentration step using headspace solid-phase microextraction and
      determination by capillary gas chromatography using flame ionisation detection.
      The influence of different parameters related to the isolation and concentration
      step, such as ethanol concentration, ionic strength, sample volume, time and
      temperature of extraction, was studied. The developed method enabled recoveries
      >91% for the analyzed compounds with limits of detection between 0.007 and 0.027
      mg/l, all of them lower than the range of concentrations found in rum samples.
      The method was successfully applied to the analysis of fatty acid ethyl esters in
      different commercial white rums.

PMID- 12058919
TI  - Parabolic-Lorentzian modified Gaussian model for describing and deconvolving
      chromatographic peaks.
AB  - A new mathematical model for characterising skewed chromatographic peaks, which
      improves the previously reported polynomially modified Gaussian (PMG) model, is
      proposed. The model is a Gaussian based equation whose variance is a combined
      parabolic-Lorentzian function. The parabola accounts for the non-Gaussian shaped
      peak, whereas the Lorentzian function cancels the variance growth out of the
      elution region, which gives rise to a problematic baseline increase in the PMG
      model. The proposed parabolic-Lorentzian modified Gaussian (PLMG) model makes a
      correct description of peaks showing a wide range of asymmetry with positive
      and/or negative skewness. The new model is shown to give better fittings than
      other models as the Li, log-normal or Pap-Papai models, which have a different
      mathematical basis. The model parameters are also related to peak properties as
      the skewness and kurtosis. The PLMG model is applied to the deconvolution of
      peaks in binary mixtures of structurally related compounds that are highly
      overlapped (retention times in min): oxytetracycline (9.00)--tetracycline
      (10.20), sulfathiazole (3.67)--sulfachloropyridazine (3.93), and sulfisoxazole
      (5.14)--sulfapyridine (5.24). The use of non-linear least-squares calibration in
      combination with the PLMG model gave superior results than the classical multiple
      linear least-squares and partial least-squares regressions. The proposed method
      takes into account run to run changes in retention time that occur along the
      injection of standards and samples, and the possible interactions that exist
      between the coeluting compounds. This decreases significantly the quantitation
      errors.

PMID- 12058920
TI  - Change of mobile phase pH during gradient reversed-phase chromatography with
      2,2,2-trifluoroethanol-water as mobile phase and its effect on the
      chromatographic hydrophobicity index determination.
AB  - We have shown previously that using a trifluoroethanol containing mobile phase
      provides a unique chromatographic selectivity. This is essential to derive
      molecular descriptors by HPLC which requires retention data from several systems.
      It also requires that the ionisation is suppressed so that retention times
      reflect the properties of the neutral molecules. Therefore the pH change of the
      mobile phase during gradient elution and its effect on the solute ionisation have
      been studied. During gradient elution of mixtures of ammonium acetate and
      butylammonium formate with trifluoroethanol as an organic modifier it was found
      that the pH was almost constant when the gradient started with a low pH. However,
      when the starting mobile phase pH was above 8 the pH dropped very quickly as the
      trifluoroethanol concentration increased in the mobile phase. The CHI descriptor
      (a retention index derived directly from gradient retention times) of several
      basic compounds as a function of starting mobile phase pH has been measured using
      trifluoroethanol gradient. The effect of the trifluoroethanol on the pKa change
      of the compounds has been investigated. The experimental data fit closely to a
      previously derived equation that describes gradient retention times as a function
      of mobile phase pH and analyte ionisation constant (pKa). This equation makes it
      possible to predict the CHI descriptor for ionisable compounds at various pH
      values. We have used butylamine for high pH mobile phase preparation as is more
      basic than ammonia and for many basic drugs the retention of the neutral form
      could be obtained directly (without extrapolation).

PMID- 12058921
TI  - Binding of ionic surfactants to charged polymer brushes grafted onto porous
      substrates.
AB  - A polymer brush containing a sulfonic acid group was appended onto the pore
      surface of a porous hollow-fiber membrane about 1 mm thick. During the permeation
      of a N-alkylpyridinium chloride (CnPyCl; n=4, 12, and 16) solution, the feed
      concentration of which ranged from 0.10 to 500 mM, through the pores at a
      constant transmembrane pressure of 0.2 MPa, C12PyCl was bound to the charged
      polymer brush. Prepermeation of a magnesium chloride solution through the pores
      was effective in regaining the liquid permeability via ionic crosslinking of the
      charged groups with the magnesium ion at a degree of crosslinking of 54%. The
      charged polymer brush captured C12PyCl without releasing the magnesium ion. At a
      surfactant concentration of about 70% of its critical micelle concentration, the
      equilibrium binding capacity of the charged polymer brush started to decrease due
      to micelle formation. In contrast, C4PyCl and PyCl without micelle formation
      increased the equilibrium binding capacity with increasing concentration while
      expelling the magnesium ion.

PMID- 12058922
TI  - Minimal number of chromatographic test parameters for the characterisation of
      reversed-phase liquid chromatographic stationary phases.
AB  - This paper focuses on the classification or differentiation of RP-HPLC columns
      based on measured chromatographic properties. A chemometric study has been
      conducted on a published data set consisting of 85 RP-HPLC columns and on a data
      set consisting of 47 self-tested columns. Principal component analysis enables
      determination of the number of parameters necessary for a rational
      differentiation. The results show that reducing the number of parameters for such
      differentiation still allows classification of the columns just as a higher
      number did. It is shown that three test parameters produce a classification
      similar to that obtained with five parameters.

PMID- 12058923
TI  - Headspace solid-phase microextraction analysis of 3-alkyl-2-methoxypyrazines in
      wines.
AB  - A procedure to determine 3-alkyl-2-methoxypyrazines in wines is described. It is
      based on the headspace solid-phase microextraction (HS-SPME) technique after a
      clean-up of the sample by distillation (previously acidified to pH 0.5) to remove
      ethanol and other volatile compounds that can interfere in the SPME.
      Determination is performed by means of capillary gas chromatography using a
      nitrogen-phosphorus detector. The method allows quantification of 3-isobutyl-2
      methoxypyrazine, 3-sec-butyl-2-methoxypyrazine and 3-isopropyl-2-methoxypyrazine
      at their natural concentration levels and below their sensory thresholds in
      Cabernet Sauvignon and Merlot wines. The method was successfully applied to
      experimental red wines and the evolution of their pyrazine contents during the
      winemaking process was monitored. Pyrazine content increased during the first
      maceration day but did not change significantly during alcoholic and malolactic
      fermentation. Final contents in wines were 12-27 ng/l of 3-isobutyl-2
      methoxypyrazine and 5-10 ng/l of 3-sec-butyl-2-methoxypyrazine.

PMID- 12058924
TI  - Solvent effect on protein binding by polymer brush grafted onto porous membranes.
AB  - An epoxy-group-containing polymer chain was grafted onto the hollow-fiber form of
      a porous polyethylene membrane by the immersion of the electron beam-irradiated
      trunk polymer in glycidyl methacrylate diluted with methanol and 1-butanol. The
      epoxy group density ranged from 8.5 to 13.4 mol per kg of the trunk polymer.
      Subsequently, the epoxy groups produced were converted into sulfonic acid and
      diethylamino groups. The density of -SOH and -N(C2H5), groups was 0.40 and 2.2
      mol per kg of the product. respectively. The polymer brush, defined as a polymer
      chain extending from the surface of a pore toward the interior of the pore, was
      evaluated from the determination of an equilibrium binding capacity of hen egg
      lysozyme (HEL) and bovine serum albumin (BSA). The polymer brush prepared in 1
      butanol was found to be longer than that prepared in methanol from the
      determinations of liquid permeability and protein adsorptivity. The proteins were
      bound to the polymer brush prepared in 1-butanol, followed by the
      functionalization, at higher degrees of multilayer binding: about 30 for HEL and
      6 for BSA.

PMID- 12058925
TI  - Comparison of histidine-tag capture chemistries for purification following
      chemical extraction.
AB  - The purification of a 6x-histidine tagged viral coat protein (L1) in expanded
      mode directly following chemical extraction from the cytoplasm of Escherichia
      coli HMS174(DE3) is investigated. Chelating adsorbents based on the ligands
      iminodiacetic acid (IDA) and nitrilotriacetic acid, using chelated metal ions
      Ni2+ and Cu2+, were compared. The use of Ni2+-IDA resulted in a high purification
      factor (9.7) and moderate recovery yield (58%). However, the eluted fractions had
      an overall L1 purity less than 50% and were therefore significantly contaminated
      with other host proteins. In batch tests, Cu2+-IDA was found to be superior to
      all other combinations as it was characterised by higher binding capacities and
      faster adsorption kinetics. A subsequent immobilised metal affinity
      chromatography-expanded bed adsorption experiment using Cu2+-IDA resulted in a
      higher L1 purification factor (20), recovery yield (71%) and purity (89%). The
      process presented here combines direct chemical extraction with expanded bed
      recovery. It is simpler than traditional methods, and should find more widespread
      application in the recovery of inclusion body proteins. Robust pseudo-affinity
      ligands such as metal chelates show potential for selective primary recovery of
      unfolded proteins, and could be used for further processing such as on-column
      refolding.

PMID- 12058926
TI  - Analysis of spectinomycin by liquid chromatography with pulsed electrochemical
      detection.
AB  - Until now, no LC method is described to determine the purity and content of
      spectinomycin without prior derivatization. A reversed-phase ion-pair LC method
      using a base deactivated column and pulsed electrochemical detection is
      described. The mobile phase consisted of an aqueous solution containing 5.8 g/l
      pentafluoropropionic acid, 1.25 g/l potassium dihydrogen phosphate and 5.5 ml/l
      tetrahydrofuran. The pH was adjusted to 6.25 using dilute NaOH solution. An
      experimental design was used to optimize the chromatographic parameters and to
      check the robustness. The quality of separation was investigated on different
      stationary phases. The method allows the separation of spectinomycin from its
      related substances as well as some other components of unknown identity. The
      total time of analysis is 65 min. A number of commercial samples were examined
      using this method.

PMID- 12058927
TI  - Study of the feasibility of focused microwave-assisted soxhlet extraction of N
      methylcarbamates from soil.
AB  - A study of the feasibility of a focused microwave-assisted Soxhlet device for the
      extraction of N-methylcarbamates from soil has been performed. The main factors
      contributing to the extraction efficiency-namely microwave power, irradiation
      time and number of cycles--were optimized by means of a two-level full factorial
      design. The extracts were analysed by HPLC-post-column fluorescence
      derivatization-detection at excitation wavelength 340 nm and emission wavelength
      445 nm. The method has allowed the extraction of carbamate pesticides from
      contaminated soil with quantitative recoveries, similar to those provided by the
      US Environmental Protection Agency method 8318, without degradation of the target
      compounds during the extraction and using less organic solvent, as 75-80% of the
      extractant was recycled.

PMID- 12058928
TI  - Dynamic chelation ion chromatography of transition and heavy metal ions using a
      mobile phase containing 4-chlorodipicolinic acid.
AB  - The chromatographic behaviour of selected transition and heavy metal ions, the
      lanthanides, uranium and aluminium, on a neutral polystyrene-divinylbenzene (PS
      DVB) stationary phase (7 microm Hamilton PRP-1) dynamically modified with 4
      chlorodipicolinic acid, was investigated to evaluate retention characteristics.
      Complicated retention factor against pH plots were found for these metals
      demonstrating changes in retention order. It was concluded that complexation
      between the metal ions and the ligand adsorbed on the resin was strongly
      influenced by the decrease in dynamic loading with increase in pH, coinciding
      with changes in the metal-to-ligand ratio in the mobile phase. Possible reversed
      phase interactions between metal-chlorodipicolinic acid complexes and the
      hydrophobic PS-DVB stationary phase also could not be ruled out. An eluent of
      0.25 mM chlorodipicolinic acid, I M potassium nitrate at pH 2.2 was suitable for
      the separation of seven transition and heavy metal ions in under 20 min on a 250
      x 4.6 mm column (with 50-mm guard column), determined in a certified water sample
      with good accuracy (R2 > or = 0.994) and reproducibility (RSD 1-4.2%). Pb(II),
      Cd(II) and Cu(II) were additionally analysed in <10 min in a more complicated
      certified rice flour matrix, using the same eluent but adjusted to pH 1.5, again
      with good accuracy (R2 > or = 0.998) and reproducibility (RSD 0.48-1.38%).

PMID- 12058929
TI  - Effects of solvent density on retention in gas-liquid chromatography. I. Alkanes
      solutes in polyethylene glycol stationary phases.
AB  - Gas-liquid chromatographic columns were prepared coating silica capillaries with
      poly(oxyethylene) polymers of different molecular mass distributions, in the
      range of low number-average molar masses, where the density still varies
      significantly. A novel, high-temperature, rapid evaporation method was developed
      and applied to the static coating of the low-molecular-mass stationary phases.
      The analysis of alkanes retention data from these columns reveals that the
      dependence of the partition coefficient with the solvent macroscopic density is
      mainly due to a variation of entropy. Enthalpies of solute transfer contribute
      poorly to the observed variations of retention. Since the alkanes solubility
      diminishes with the increasing solvent density, and this variation is weakly
      dependent with temperature, it is concluded that the decrease of free-volume in
      the liquid is responsible for this behavior.

PMID- 12058930
TI  - Gas chromatography for in situ analysis of a cometary nucleus III. Multi
      capillary column system for the cometary sampling and composition experiment of
      the Rosetta lander probe.
AB  - The cometary sampling and composition (COSAC) experiment is one of the principal
      experiments of the surface lander probe of the European Space Agency Rosetta
      mission to be launched in January 2003. The instrument is designed for the in
      situ chemical analysis of a cometary nucleus as the details of the nucleus
      composition are of primary importance for understanding both the formation of the
      solar system, and the origin of life on Earth. The COSAC experiment consists of
      an evaporation/pyrolysis device and two analytical systems: a multi-column gas
      chromatograph and a high-resolution time-of-flight mass spectrometer which may
      either be operated alone or in a coupled mode. The gas chromatograph includes
      five general purpose chromatographic columns and three chiral ones, all mounted
      in parallel. Taking into account the chemical species potentially present in the
      cometary nucleus as well as the space constraints, a set of five complementary
      columns was selected to perform the separation and identification of the
      compounds present in the cometary nucleus. This set of columns includes a carbon
      molecular sieve porous-layer open tubular (PLOT) column used for the separation
      of both the noble and other permanent gases, and the C1-C2 hydrocarbons. A second
      PLOT column uses a divinylbenzene-ethylene glycol-dimethylacrylate porous polymer
      as stationary phase for the analysis of a wide range of C1-C2 organic molecules,
      Two complementary wall-coated open tubular (WCOT) columns with
      polydimethylsiloxane (PDMS) liquid stationary phases, one containing cyanopropyl
      phenylsiloxane and the other diphenylsiloxane groups, are designed to target the
      same range of organic compounds (C3-C7) which could be representative of the
      widest range of cometary compounds. A third WCOT column with an apolar stationary
      phase made of non-substituted PDMS is used for the separation and identification
      of higher-molecular-mass compounds (up to C10) and aromatic species (monoaromatic
      and polyaromatic). This paper describes these five general-purpose capillary PLOT
      and WCOT columns, selected to be used in the COSAC GC system. The analytical
      capabilities are examined with a special emphasis on the exobiological and
      planetological implications.

PMID- 12058931
TI  - Adsorption kinetics of beta-lactoglobulin on a polyclonal immunochromatographic
      support.
AB  - Beta-Lactoglobulin is one of the main components of whey proteins. Among other
      reasons, its allergenicity makes its determination in hypoallergenic foods and
      bio-pharmaceutical products necessary. Immunoaffinity chromatography is a widely
      accepted technique for purification and analysis of proteins. Knowledge of the
      apparent kinetics of the adsorption of beta-lactoglobulin onto the anti-beta
      lactoglobulin immunochromatographic column is important to optimize the
      analytical process. High-performance frontal affinity chromatography was used to
      study the apparent kinetics of the adsorption process. Langmuir and bi-Langmuir
      kinetic models, assuming one and two kinds of binding sites, respectively, were
      used to characterize the adsorption kinetics of beta-lactoglobulin B on a
      polyclonal immunoadsorbent. Very good fits were obtained with the bi-Langmuir
      model for two different concentrations of beta-lactoglobulin and this allowed us
      to calculate the apparent adsorption rate constants and the column capacities for
      both kinds of sites. Experimental results indicate the possibility that the
      adsorption process is not irreversible. The values of the apparent dissociation
      rate constants leading to the best fit were estimated and the affinity constants
      were calculated.

PMID- 12058932
TI  - C2-C8 hydrocarbon measurement and quality control procedures at the Global
      Atmosphere Watch Observatory Hohenpeissenberg.
AB  - A new automated on-line GC-flame ionization detection system for long-term
      stationary measurements of atmospheric C2-C8 hydrocarbons in the lower ppt range
      is described. The system is operated at the Global Atmosphere Watch Observatory
      Hohenpeissenberg (47 degrees 48'N, 11 degrees 01'E) in rural south Germany.
      Atmospheric mixing ratios of more than 40 different hydrocarbons can be
      continuously measured in 80 min time intervals. Corresponding detection limits
      are below 3 ppt, except for propene, butenes and benzene (about 10 ppt). Detailed
      quality assurance and quality control protocols are described which are applied
      to routine operation and data analysis. The various error contributions, overall
      precision, and accuracy for all measured compounds are discussed in detail.
      Typical ambient air mixing ratios are in the range of a few ppt to a few ppb, and
      corresponding measurement accuracies are below 10% or 10 ppt. For less than 20%
      of the analyzed compounds measurement accuracies are worse, mainly because of
      insufficient peak separation, blank values or reduced reproducibilities. The
      present system was tested in international intercomparison experiments (NOMHICE,
      AMOHA). For most of the C2-C8 hydrocarbons analyzed, our results agreed better
      than +/- 10% (20% NOMHICE phase 5) or +/- 10 ppt with the corresponding reference
      values.

PMID- 12058933
TI  - Analyses of the wood preservative component N-cyclohexyl-diazeniumdioxide in
      impregnated pine sapwood by direct thermal desorption-gas chromatography-mass
      spectrometry.
AB  - Investigations concerning the qualitative and quantitative determination of the
      organic wood preservative component N-cyclohexyl-diazeniumdioxide (HDO) in
      treated timber were carried out by means of direct thermal desorption-gas
      chromatography-mass spectrometry (DTD-GC-MS). It could be shown that the
      identification of HDO in treated pine sapwood (Pinus sylyestris L.) is relatively
      simple using this analytical technique. Quantification of this active ingredient
      can be carried out using the peak area of the specific mass fragment m/z 114. A
      calibration curve with a high correlation coefficient was obtained in the range
      from 40 to 550 mg HDO per kg timber. Furthermore it can be deduced that the
      results obtained are characterised by an excellent reproducibility with standard
      deviations ranging from 5 to 10% in general. For the chosen experimental set up a
      detection limit of 4 mg HDO per kg treated pine sapwood was calculated, although
      merely 20% of the active ingredient was desorbed.

PMID- 12058934
TI  - Evaluation of an extraction method in the determination of the 2,4,6
      trichloroanisole content of tainted cork.
AB  - A method based on solvent extraction and GC-electron-capture detection analysis
      for the determination of 2,4,6-trichloroanisole (TCA) from cork has been
      evaluated and optimised. Our sample treatment consists of an extraction stage
      with pentane while the sample and solvent are kept in contact in a mechanical
      shaker (shake-flask extraction). Different extraction conditions have been tested
      in order to find the best compromise between efficiency and time of analysis.
      Different columns were evaluated for use in the concentration and purification
      step. A silica column was found to give the best performance in terms of recovery
      of TCA and repeatability. Pentane and mixtures of pentane-diethyl ether at
      different ratios were tested as eluting agents. It was found that 10 ml pentane
      allowed the recovery of retained TCA. Finally, the eluate was concentrated and
      injected into the chromatograph for TCA determination. The optimised
      chromatographic conditions enabled the quantification of TCA and 2,6
      dichloroanisole, which was assayed as the internal standard. The shake-flask
      extraction method was compared with Soxhlet and ultrasound assisted extraction
      procedures using pentane as a solvent. Similar results were obtained for the
      shake-flask and Soxhlet extraction methods, while sonication gave significantly
      lower recoveries. The optimised shake-flask method was applied to determine the
      distribution of TCA in naturally contaminated cork bark.

PMID- 12058935
TI  - Determination of benzylsuccinic acid in gasoline-contaminated groundwater by
      solid-phase extraction coupled with gas chromatography-mass spectrometry.
AB  - Benzylsuccinic acid (BSA) and methylbenzylsuccinic acid (methyl-BSA) are
      unambiguous biotransformation products resulting from anaerobic toluene and
      xylene biodegradation, respectively. A solid-phase extraction method based on
      polystyrene-divinylbenzene sorbent was developed for the quantitative BSA
      determination in groundwater samples as an alternative to liquid-liquid
      extraction. Gas chromatography coupled with mass spectrometry was used for
      separation and detection. The recovery from spiked 11 groundwater samples was 88
      to 100%. The precision of the method, indicated by the relative standard
      deviation, was +/- 4% and the method detection limit was 0.2 microg/l. The
      concentration of BSA and methyl-BSA in groundwater samples from anaerobic BTEX
      (benzene, toluene, ethylbenzene and xylenes)-contaminated sites ranged from below
      the detection limit (3 microg/l) to 155 microg/l.

PMID- 12058936
TI  - Increase of sample load without peak deterioration by careful selection of
      electrolyte in capillary zone electrophoresis.
AB  - In this study it is demonstrated that much higher concentrations of bases
      dissolved in water can be injected in capillary zone electrophoresis without
      causing peak deterioration, e.g., peak splitting, if it is the co-ion that
      buffers instead of the counter-ion. Those findings can be utilised to control
      peak shapes and in this way an increase in the sample load and indirectly a
      decrease in the detection limits of impurities in the sample can be obtained.
      Good results were obtained with 4-aminobutyric and 6-aminocaproic acids as
      buffering co-ions. Another possibility evaluated successfully was that of using a
      dibasic acid, malic acid or succinic acid. With an electrolyte containing both
      succinic acid and 6-aminocaproic acid at pH 4.5, it was possible to load at least
      10-20 times more of the test substances imidazole, creatinine or 2
      aminopyrimidine dissolved in water than with an electrolyte at the same pH
      containing acetic acid and tris(hydroxymethyl)aminomethane.

PMID- 12058937
TI  - Capillary electrochromatography of peptides on a column packed with tentacular
      weak cation-exchanger particles.
AB  - Silica-based, tentacular weak cation-exchanger particles were prepared for use as
      the stationary phase in the separation of positively charged sample components by
      capillary electrochromatography (CEC). Silica beads were first silanized with 3
      (trimethoxysilyl) propyl methacrylate that served as a heterobifunctional linker,
      which reacted with 2-acrylarmidoglycolic acid in a second step by radical
      polymerization in aqueous solution. Baseline separation of basic peptides with
      good column efficiency was obtained on packed capillary columns by isocratic
      elution CEC with NaCl as the mobile phase modulator. The retention mechanism in
      the electrochromatographic process was studied by examining the effect of salt
      concentration on the migration behavior of the peptides. The chromatographic
      retention factor k'(lc) for charged sample components in the
      electrochromatographic process was estimated on the assumption that the overall
      migration rate of a charged migrant can be taken as the sum of the rate of
      chromatographic elution and the rate of electrophoretic migration. The estimated
      k(lc) values from experimental results were plotted against the molal salt
      concentration on a double logarithmic scale. The linear correlation is in good
      agreement with the prediction by the theory on the basis of traditional ion
      exchange chromatography. The comparison of CEC results, obtained with open
      tubular and packed capillary columns having the same retentive functions as the
      stationary phase, supports the notion that variation of the phase ratio in the
      column offers an additional means to modulate the electrochromatographic
      migration behavior.

PMID- 12058938
TI  - Capillary electrophoretic separation of phenolic diterpenes from rosemary.
AB  - The major phenolic diterpenes responsible for the antioxidant properties of
      rosemary extracts, namely carnosol and carnosic acid, were separated by capillary
      zone electrophoresis (CZE) using a 56 cm long uncoated fused-silica capillary and
      a 50 mM disodium tetraborate buffer of pH 10.1. The effect of the buffer type, pH
      and concentration, and the capillary length on the separation, was studied.
      Carnosol and carnosic acid were identified in the electrophoregrams of rosemary
      extracts through their migration times and UV spectra obtained by CZE analysis of
      pure compounds isolated from a rosemary extract by HPLC fractionation. The CZE
      method had good reproducibility (relative standard deviation less than 5%) and
      was applied to compare the contents of carnosol and carnosic acid in solid and
      oil-dispersed commercial extracts of rosemary and in rosemary leaves. The
      separation of carnosol and carnosic acid was accomplished in less than 11 min.

PMID- 12058939
TI  - Separation and simultaneous determination of water-soluble and fat-soluble
      vitamins by electrokinetic capillary chromatography.
AB  - A comparative study of different surfactants, such as sodium dodecyl sulfate and
      bis(2-ethylhexyl) sodium sulfosuccinate (AOT), as pseudostationary phases was
      conducted in order to find the best conditions for the separation of the water-
      and fat-soluble vitamins by electrokinetic capillary chromatography. Separation
      was accomplished with AOT in a water-acetonitrile solution in the presence of
      boric acid-sodium borate buffer. A study of different variables was performed in
      order to obtain the best resolution and quantification of the vitamins: the
      variables explored were the pH and concentration of the buffer used, the
      percentage of acetonitrile, the concentration of surfactant and the applied
      voltage. Calibration curves and precision data were obtained for each analyte.
      Finally, a method to analyze these substances in pharmaceutical preparations is
      proposed.

PMID- 12058940
TI  - Continuous fractionation of enantiomer pairs in free solution using an
      electrophoretic analog of simulated moving bed chromatography.
AB  - Continuous fractionation of the left and right enantiomers of Piperoxan was
      performed in free solution in a vortex-stabilized electrophoresis apparatus.
      Sulfated beta-cyclodextrin was used as the chiral selector. A capillary
      electrophoresis (CE) study of the separation of Piperoxan enantiomers was carried
      out in order to find the buffer conditions that produce the maximum peak
      separation time between the two enantiomers and the optimal chiral selector
      concentration. These peak separation times were then used to calculate the
      electrophoretic mobilities of the enantiomer-ligand complexes. The difference in
      electrophoretic mobilities, when used in a preliminary model of the enantiomer
      separation, indicated that, by imposing a fluid flow opposite the direction of
      electromigration, it would be possible to force the fast and slow enantiomers to
      move in opposite directions within the vortex-stabilized apparatus. Using the
      predictions of the preliminary separation model, the vortex stabilized
      electrophoresis apparatus was configured with a feed port at the center of the
      chamber axis and offtake ports near the cathode and anode. This allowed for
      continuous operation of the apparatus. Continuous fractionations were completed
      at throughputs of 1.5 and 4.0 mg/h with both offtakes showing greater than 99%
      enantiomeric purity at 4.0 mg/h using CE. Fractionation was achieved at a
      throughput of 10 mg/h, but while the slow enantiomer was recovered with greater
      than 99% purity, only 96% enantiomeric purity of the fast stereoisomer was
      achieved. The loss of resolution at higher volumetric throughputs supports our
      hypothesis that a mobility-dependent "window" of operation exists in which two
      solutes can be completely separated.

PMID- 12058941
TI  - Determination of sildenafil citrate and its main metabolite by sample stacking
      with polarity switching using micellar electrokinetic chromatography.
AB  - Micellar electrokinetic capillary chromatography (MEKC) coupled with sample
      stacking and polarity switching was investigated for the determination of Viagra
      (sildenafil citrate, SC) and its metabolite (UK-103,320, UK) in human serum in
      the concentration range of clinical interest. Human serum samples spiked with SC
      and UK were eluted with methanol from a C18 cartridge, the extract was evaporated
      and regenerated in a solution that contained 1 mM phosphate buffer (pH 12.3) and
      20% methanol. The MEKC separation was performed using an injection time of 275 s,
      a polarity switching time of 93 s, a phosphate buffer, (pH 12.3, 15 mM)
      containing 25 mM sodium dodecyl sulfate as separation electrolyte and a fused
      silica capillary. The analysis takes about 6 min and gives satisfactory inter-day
      precision with respect to migration times and linear responses over the 80-900
      ng/ml concentration range investigated for SC and UK. Intra-day RSDs (n=4 graphs)
      for the slopes of the calibration graphs were 4.86% for SC and 3.50% for UK.
      Inter-day RSDs for the slopes were 4.37% for SC and 5.39% for UK. Detection
      limits (S/N=3) were about 17 ng/ml for both compounds in human serum. A 1-ml
      volume of blood serum was necessary to do this determination.

PMID- 12058942
TI  - Use of on-line liquid chromatography-nuclear magnetic resonance spectroscopy for
      the rapid investigation of flavonoids from Sorocea bomplandii.
AB  - This paper reports the identification of di- and triglycosylated flavonoids from
      Sorocea bomplandii (Moraceae) by liquid chromatography coupled on-line to nuclear
      magnetic resonance (LC-NMR). These glycosylated flavonoids may be used as a
      taxonomic marker in future work.

PMID- 12058943
TI  - Analysis of conjugated linoleic acid-enriched triacylglycerol mixtures by
      isocratic silver-ion high-performance liquid chromatography.
AB  - Silver-ion HPLC (Ag-HPLC) was applied to the fractionation of a triacylglycerol
      (TAG) sample enriched (>80%) with conjugated linoleic acid (CLA). After
      conversion of the TAGs to fatty acid methyl esters using sodium methoxide in
      methanol, Ag-HPLC (dual-column; isocratic solvent system of 0.1% acetonitrile in
      hexane; UV detection at 233 nm) was used to determine the CLA isomer distribution
      (50:50 mixture of 9c 11t- and 10t,12c-18:2). Three or four Ag-HPLC columns
      connected in series (0.6-1.0% acetonitrile in hexane as solvent; UV detection at
      206 nm) were used to analyze the sample in TAG form. Elution times for CLA
      enriched TAGs averaged 30 min or less. Isocratic solvent conditions were used to
      eliminate the solvent equilibration times (often 30 min or more) required between
      sample injections when solvent programming is used. The ratio of TAGs containing
      three vs. only two CLA molecules was found to be approximately 3 to 1. Ag-HPLC
      has thus been shown to be a useful method for rapidly analyzing not only CLA
      isomers as esters, but also in the TAG form.

PMID- 12058944
TI  - Fast ion chromatography of common inorganic anions on a short ODS column
      permanently coated with didodecyldimethylammonium bromide.
AB  - Fast ion-exchange chromatography has been developed and applied to the separation
      of common inorganic anions. Using a didodecyldimethylammonium bromide (DDAB)
      coated short (30 mm x 4.6 mm) ODS analytical column (3-microm particle size) and
      a 5 mM phthalate eluent (pH 7.5) the isocratic separation of nine common anions
      in 160 s was possible, with the first seven anions, including phosphate, chloride
      and sulphate, separated within 65 s. Detection was achieved using indirect UV at
      279 nm. The high capacity, highly hydrophobic ion-exchange coating demonstrated
      excellent stability over time, even at elevated temperatures (45 degrees C) and
      exhibited unusual selectivity for common anions (retention order=fluoride,
      carbonate, phosphate, chloride, bromate, nitrite, sulphate, bromide and nitrate).
      The developed chromatography was successfully applied to the rapid analysis of
      river water and seawater samples.

PMID- 12058945
TI  - Analysis of peak asymmetry in chromatography.
AB  - The knowledge of the symmetry of chromatographic peaks is extremely important
      regarding the digital signal processing. The significant deviation of the peak
      shape from the symmetrical peak makes hardly possible the acquisition of
      chromatographic signal information, such as the retention time, the peak area,
      the peak width at half peak height, the peak overlapping, etc. In the literature
      one can find many methods for the determination of the asymmetry factor. For
      example it is suitable to calculate the skewness from the third central moment.
      However in case of noisy baseline the value of the skewness oscillates highly
      depending on the number of points used for the mathematical calculation. In this
      work a new method is presented for the determination peak shape asymmetry. We
      order mathematical function to the chromatographic peaks by fitting, and then
      symmetrical curve is generated with the same peak maximum position and height,
      the peak width is fitted. The difference of the two functions is constituted and
      areas of the data differences are calculated, which are really characteristics of
      the peak asymmetry. Correlation between the area of the difference signal and the
      asymmetry factor is established. The method was applied for different types of
      chromatographic peak shapes and the results were interpreted.

PMID- 12058946
TI  - Immobilized artificial membrane liquid chromatography: proposed guidelines for
      technical optimization of retention measurements.
AB  - The objectives of this study were to establish guidelines for the proper
      measurement of capacity factors (log k(IAMw) on immobilized artificial membrane
      (IAM) stationary phases. In this context, some aspects related to the
      extrapolation of log(kIAMw) values, the stability and properties of IAM.PC.DD2
      stationary phases and the column-to-column variability are discussed. No
      significant difference was observed when using either acetonitrile or methanol
      for the linear extrapolation of log k(IAM) values. However, methanol seems more
      appropriate when working with ionized compounds. Plotting isocratic capacity
      factors against the percentage (v/v) of co-solvent instead of the mole fraction
      leads to more reliable log k(AMW) values. Furthermore, our results with a YMC ODS
      AQ and an IAM.PC.DD2 HPLC column indicate that only small differences arise
      between extrapolated capacity factors when using the (w(w))pH or the (s(w))pH
      operational scale and correcting or not the ionic strength for dilution caused by
      the co-solvent. The use of the (s(w))pH scale is recommended when working with
      ionized compounds in order to avoid parabolic relationships during linear
      extrapolation. The pH-dependent retention of three ionizable drugs on an
      IAM.PC.DD2 phase showed that secondary interactions with the charged moieties of
      the chromatographic surface affect the retention of ionized compounds around
      physiological pH. Finally, it was shown that column ageing occurs also with
      IAM.PC.DD2 stationary phases and that it depends on the column as well as on the
      investigated analyte. The intra-batch variability for IAM.PC.DD2 phases was
      small, whereas a marked and solute-dependent batch-to-batch variability was
      apparent.

PMID- 12058947
TI  - Study of the adsorption equilibria of the enantiomers of 1-phenyl-1-propanol on
      cellulose tribenzoate using a microbore column.
AB  - Using competitive frontal analysis, the binary adsorption isotherms of the
      enantiomers of 1-phenyl-l-propanol were measured on a microbore column packed
      with a chiral stationary phase based on cellulose tribenzoate. These measurements
      were carried out using only the racemic mixture. The experimental data were
      fitted to four different isotherm models: Langmuir, BiLangmuir, Langmuir
      Freundlich and Toth. The BiLangmuir and the Langmuir-Freundlich models accounted
      best for the competitive adsorption data. An excellent agreement between the
      experimental and the calculated overloaded band profiles for various samples of
      racemic mixture was obtained when the equilibrium dispersive model of
      chromatography was used together with the BiLangmuir competitive isotherm. The
      isotherm parameters measured under competitive conditions were used to calculate
      the overloaded band profiles of large samples of the pure S- and R-enantiomers,
      too. A satisfactory agreement between the experimental and calculated band
      profiles was observed when using in the computation the corresponding single
      component BiLangmuir isotherm derived from the binary isotherm previously
      determined. Thus oniy data derived from the racemic mixture are required for
      computer optimization of the preparative chromatography separation of the
      enantiomers.

PMID- 12058948
TI  - Evaluation of the stability and selectivity for various adjustable stationary
      phases using zirconium oxide supports in high-performance liquid chromatography.
AB  - The selectivity and retention properties of a zirconia stationary phase were
      reversibly altered using various ligands containing Lewis base functional groups.
      A simple loading procedure allowed a variety of ligands to be attached to the
      zirconia surface via Lewis interactions. The resulting stationary phases were
      shown to be stable and produced different selectivity and retention properties
      from the native zirconia material. The metal oxide adsorbent was converted to a
      diol-type stationary phase using glucose-6-phosphate for use under normal-phase
      conditions. Reversed-phase supports were produced by loading either octyl- or
      octadecylphosphonic acid onto the native zirconia support. The properties of
      these new phases were then compared to commercially available bonded silica
      analogs. Ligands bound to the surface in this manner were effectively removed and
      the native zirconia was regenerated using a dilute base wash procedure.

PMID- 12058949
TI  - Optimisation of headspace solid-phase microextraction for analysis of aromatic
      compounds in vinegar.
AB  - Headspace solid-phase microextraction has been applied to the analysis of aroma
      compounds in vinegar. Silica fibre coated with Carboxen-polydimethylsiloxane was
      found to be more efficient at extracting these compounds than other fibres such
      as those coated with polydimethylsiloxane, Carbowax-divinylbenzene, and
      polydimethylsiloxane-divinylbenzene, but its repeatability was low. Different
      parameters such as extraction time, temperature of the sample during the
      extraction, ionic strength, and sample volume were optimised using a two-level
      factorial design expanded further to a central composite design. This chemometric
      tool is very appropriate in screening experiments where the aim is to investigate
      several possibly influential and/or interacting factors. The extraction
      efficiency is inversely affected by the acetic acid content-an increase in the
      acetic acid concentration decreases the extraction efficiency. No interference is
      observed with the increase in content of polyphenols.

PMID- 12058950
TI  - Solid-phase microextraction coupled to high-performance liquid chromatography to
      determine phenolic compounds in water samples.
AB  - Solid-phase microextraction (SPME) coupled to high-performance liquid
      chromatography (HPLC) with ultraviolet (UV) and electrochemical detection (ED)
      has been applied to determine 11 phenolic compounds considered priority
      pollutants by the US Environmental Protection Agency. 85 microm polyacrylate
      fibers were used to extract the analytes from the aqueous samples. Two different
      designs of the liquid chromatograph were compared in combination with SPME.
      Dynamic and static modes of desorption in both HPLC designs were compared and the
      variables affecting both absorption and desorption processes in SPME-HPLC were
      optimized. Static desorption in both HPLC systems showed better recoveries for
      the phenolic compounds. The performance of the SPME-HPLC-UV-ED method was
      evaluated with river water and wastewater samples. The method enabled the
      determination of phenolic compounds at low levels in these water samples.

PMID- 12058951
TI  - Liquid exclusion-adsorption chromatography: a new technique for isocratic
      separation of non-ionic surfactants. V. Two-dimensional separation of fatty acid
      polyglycol ethers.
AB  - Fatty acid polyglycol esters can be fully characterized using two-dimensional
      liquid chromatography with liquid chromatography under critical conditions (LCCC)
      as the first and liquid exclusion-adsorption chromatography (LEAC) as the second
      dimension. LEAC is run under isocratic conditions, which allows the use of the
      refractive index detector, and thus accurate quantitation. Fractions from LCCC
      are transferred to LEAC using the full adsorption-desorption technique, by which
      they are focussed and reconcentrated before injection into the second dimension.
      This is achieved by increasing the water content of the mobile phase behind the
      LCCC column. Monoester oligomers of up to 20 oxyethylene units can be resolved to
      the baseline. Diester oligomers are partially separated in the first dimension
      (LCCC).

PMID- 12058952
TI  - The glucocorticoid receptor: molecular mechanisms and new therapeutic
      opportunities.

PMID- 12058953
TI  - What can we learn from the synovium in early rheumatoid arthritis?
AB  - Rheumatoid arthritis (RA) affects approximately 1% of the population and is a
      chronic inflammatory joint disease resulting in joint destruction, increased
      morbidity and mortality. Although the aetiology of this disease is unknown, the
      pivotal role played by cytokines and degradative enzymes in mediating
      inflammation and joint destruction, particularly early in the disease process,
      has been the focus of recent literature and will be the focus of this review. Up
      until recently, studies on early RA were limited as there was an inherent delay
      in patients reaching the rheumatologist's care and initial diagnostic confusion
      may have compounded these problems. In particular, the observation that early
      intervention improves outcome, has driven the study of early RA. It is difficult
      to define early RA but most studies have defined this as disease duration of less
      than 12 months from symptom onset. Clearly, it is important to study the synovial
      membrane in early disease, in particular to try and answer the important
      questions: (1) What are the earliest changes to occur in the RA synovium? (2) Can
      we distinguish RA on the basis of synovial membrane pathology? (3) Can synovial
      immunopathology predict outcome? (4) What is the role of arthroscopic biopsy in
      early RA?

PMID- 12058954
TI  - Nicorandil inhibits degranulation and TNF-alpha release from RBL-2H3 cells.
AB  - OBJECTIVE: Nicorandil is a potassium channel opener and nitric oxide (NO) donor,
      and the hypothesis was tested that these modes of action may inhibit cellular
      degranulation and release of tumour necrosis factor-alpha (TNF-alpha). MATERIALS
      AND METHODS: TNF-alpha and beta-hexosaminidase secretion were measured from rat
      basophilic leukemia cells (RBL-2H3) activated via the high affinity IgE receptor
      with dinitrophenyl-albumin (DNP-A) challenge in the presence of nicorandil.
      Inhibitors of K+ openers and NO were pre-incubated with the RBL-2H3 cells to
      determine the principal mode of action. RESULTS: Nicorandil significantly
      inhibited the release of TNF-alpha in a dose-dependent manner (p < 0.001, ANOVA)
      reaching a maximum inhibition of DNP-A 74.1% at 10(-3) M, (p < 0.001). Similarly
      it inhibited beta-hexosaminidase release (p < 0.001, ANOVA) with maximal
      inhibition at 10(-3) M (p < 0.001). Other K+ openers did not show this effect.
      Neither the potassium channel blocker glibenclamide nor the guanylyl cyclase
      inhibitor, ODQ, could reverse this inhibition, but when added in combination
      reduced the effect by 47%. CONCLUSIONS: Nicorandil is able to inhibit
      degranulation and TNF-alpha release of RBL cells stimulated through the IgE
      receptor, and requires both the K+ opening and nitric oxide donor activity, which
      may represent a novel method for inhibiting cytokine release.

PMID- 12058955
TI  - Protective effect of low molecular weight heparin on experimental colitis: role
      of neutrophil recruitment and TNF-alpha production.
AB  - OBJECTIVE: The purpose of this study was to examine the impact and mechanism of
      action of low molecular weight heparin (LMWH) in a model of murine colitis.
      MATERIALS AND METHODS: Balb/c mice were exposed to 5% dextran sodium sulfate
      (DSS) in the drinking water for five days. LMWH (500 units/kg/day) was
      administered by subcutaneous injection prior to and throughout the treatment
      period with DSS. Clinical disease activity index (DAI), including body weight
      loss, stool consistency and blood in feces were examined daily. Moreover, crypt
      height (CH), mucosal damage score (MDS), myeloperoxidase (MPO) activity and tumor
      necrosis factor-alpha (TNF-alpha) content in the colon were determined. RESULTS:
      DSS increased DAI, MDS, MPO activity and TNF-alpha production and decreased CH.
      Administration of LMWH markedly reduced DAI, MDS and reversed the CH-reduction.
      Moreover, in LMWH-treated animals, the MPO activity was reduced by more than 67%
      whereas mucosal levels of TNF-alpha was similar compared to DSS control mice.
      CONCLUSIONS: These findings suggest that LMWH inhibits murine colitis by
      interference with neutrophil recruitment and that LMWH may provide a novel
      pharmacological approach to treatment of inflammatory bowel disease.

PMID- 12058956
TI  - An anti-rheumatic agent T-614 inhibits NF-kappaB activation in LPS- and TNF-alpha
      stimulated THP-1 cells without interfering with IkappaBalpha degradation.
AB  - OBJECTIVE: Compound T-614, a member of the methanesulfoanilide class of anti
      inflammatory agents, shows potent anti-arthritic activity in animal models of
      rheumatoid arthritis. The aim of the present investigation was to characterize
      the anti-arthritic activity of T-614 in terms of regulation of the nuclear
      transcription factor NF-kappaB, which is associated with expression of many
      immune and inflammatory genes. MATERIALS AND METHODS: THP-1 cells (human
      monocytic leukemia cell line) were used throughout this in vitro study, and
      lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-alpha were employed for
      activation of the cells. Cytokine production was assayed by enzyme-linked
      immunosorbent assay (ELISA). The mRNA levels were determined by a semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay.
      Assessment of the NF-kappaB DNA binding activity was performed by an
      electrophoretic mobility shift assay (EMSA) using a digoxigenin (DIG)-labeled
      double-stranded oligonucleotide containing kappaB-binding site. Degradation
      kinetics of the cytosolic NF-kappaB inhibitor a (IkappaBalpha) were studied by
      Western blot analysis. RESULTS: T-614 inhibited LPS-stimulated production of TNF
      alpha, interleukin (IL)-6, and IL-8 in a concentration-dependent manner with
      decreasing mRNA levels (IL-6 and IL-8). EMSA study showed that T-614 prevented
      TNF-alpha as well as LPS-stimulated activation of NF-kappaB, and Western blot
      analysis proved that T-614 did not affect degradation of IkappaBalpha protein.
      CONCLUSIONS: These results suggest that the inhibitory effect of T-614 on the
      production of TNF-alpha, IL-6 and IL-8 in LPS-stimulated THP-1 cells may involve
      transcriptional regulation through suppression of NF-kappaB activation without
      interfering with IkappaBalpha degradation.

PMID- 12058957
TI  - A novel bioactive 31-amino acid ET-1 peptide stimulates eosinophil recruitment
      and increases the levels of eotaxin and IL-5.
AB  - OBJECTIVE AND DESIGN: Investigation of the role of a novel inflammatory mediator
      31-amino acid endothelin-1 [ET-1 (1-31)], a major ET derivative in granulocytes,
      in eosinophil recruitment after its subcutaneous administration to mice. METHODS:
      Various ET-1 derivatives (100 pmol), with or without ET receptor antagonists (200
      pmol), were administered subcutaneously to mice, and then the eosinophil
      migration into and chemokine levels in the injected loci were analyzed. RESULTS:
      ET-1 (1-31) and a 21-amino acid endothelin-1 (ET-1), but not big ET-1, induced
      eosinophil migration into the injected loci with a peak after administration for
      12 h, and increased the levels of eotaxin and interleukin-5 with peaks at 6 and
      24 h, respectively. These effects of ET-1(1-31) and ET-1 were significantly
      inhibited by an ETA receptor antagonist, BQ-123, but not by an ETB receptor
      antagonist, BQ-788. CONCLUSION: Novel bioactive ET-1 (1-31) induces local
      eosinophil migration, and increases in eotaxin and interleukin-5 through an ETA
      or ETA-like receptor.

PMID- 12058958
TI  - Effect of enrofloxacin treatment on plasma endotoxin during bovine Escherichia
      coli mastitis.
AB  - OBJECTIVE AND DESIGN: To investigate the effect of enrofloxacin on endotoxin
      resorption during bovine Escherichia coli mastitis. ANIMALS: 12 healthy early
      post partum Holstein cows. TREATMENT: Mastitis was induced by intramammary
      infusion of 10(4) cfu E. coli P4:032. Six cows were treated twice according to
      the usual enrofloxacin therapy: 5 mg/kg enrofloxacin 1) intravenously at 10 h and
      2) subcutaneously at 30 h after challenge. The other 6 cows served as non-treated
      controls. METHODS: Blood and milk samples were collected at several time points
      after challenge. LPS in plasma was quantified using the limulus amoebocyte lysate
      (LAL) assay. The somatic cell count (SCC) and cfu of milk samples were also
      analysed. RESULTS: Occasional LPS peaks were detected in the plasma of 2 control
      cows at 6 h post-challenge and of 1 enrofloxacin-treated cow at 10 h post
      challenge (P < 0.01 and P < 0.05, respectively, in comparison with time 0), just
      before enrofloxacin treatment. After enrofloxacin treatment, no significant LPS
      amounts were detected in the plasma of treated cows, but neither in the control
      cows. CONCLUSION: During induced coliform mastitis, LPS resorption in plasma
      occured only sporadically and within 10 h post-challenge. Whereas enrofloxacin
      treatment clearly limited bacterial growth in milk, significant effects on LPS
      resorption could not be detected. This suggests that enrofloxacin treatment of E.
      coli mastitis is predominantly beneficial by its bactericidal activity and is not
      associated with enhanced resorption of endotoxins.

PMID- 12058959
TI  - Effect of oral antigen administration on nasal blockage in experimental allergic
      rhinitis in guinea pigs.
AB  - OBJECTIVE AND DESIGN: We evaluated the effectiveness of oral treatment with
      Japanese cedar pollen on experimental allergic rhinitis in guinea pigs. SUBJECTS:
      Male Hartley guinea pigs. TREATMENT: From 16 days before the first sensitisation,
      1 and 100 mg/time/animal pollen suspension was orally administered twice weekly.
      Animals were then sensitised and repeatedly challenged with the pollen. METHOD:
      Guinea pigs were sensitised by intranasal instillation of cedar pollen extracts
      adsorbed onto Al(OH)3 at a dose of 0.3 microg pollen protein/0.3 mg Al(OH)3/3
      microl/nostril twice a day for 7 days. Then the animal was challenged by
      inhalation with cedar pollen (1.8 mg/nostril) once every week. We evaluated the
      effects of the oral treatment with antigen on: 1) sneezing frequency, 2) nasal
      blockage after antigen challenge, 3) nasal hyperresponsiveness to histamine and
      leukotriene D4, and 4) titres of anaphylactic antibodies. RESULTS: During the
      course of the high dose administration, several animals died from a possible
      cytotoxicity, whereas the low dose caused no discernible change. The oral
      administration of the pollen at both the doses significantly inhibited nasal
      blockage, and the hyperresponsiveness to the stimuli was also strongly suppressed
      by the oral treatment. Inhibitory effectiveness did not differ substantially
      between the 1 and 100 mg/animal-treated groups. In contrast, neither sneezing
      frequency nor the increasing level of anaphylactic antibodies was influenced by
      the oral administration. CONCLUSIONS: In this study, we found that the pollen
      induced nasal blockage and hyperresponsiveness were suppressed by the oral
      administration of the pollen in the sensitised guinea pig.

PMID- 12058960
TI  - Neutrophil hypochlorous acid production is impaired in multiple organ failure
      patients with candidaemia; reversal with antifungal agents.
AB  - OBJECTIVE AND DESIGN: Neutrophil-derived hypochlorous acid (PMN-HOCL) is a potent
      bactericidal and fungicidal agent. Neutrophils from patients with multiple organ
      failure (MOF) have an altered ability to inhibit Candida albicans. Conversely
      antifungal agents are effective in decreasing mortality in MOF patients with
      fungaemia. We determined the effect on the rate of production of PMN-HOCL in a
      series of MOF patients with C. albicans fungaemia when antifungal agents are
      administered. SUBJECTS AND METHODS: Eleven patients with MOF were recruited. Four
      patients had culture-positive C. albicans fungaemia (group 1) and 7 patients with
      MOF but without C. albicans fungaemia acted as controls (group 2). HOCL assays
      were performed on peripheral blood PMN obtained from group 1 and group 2
      patients. RESULTS: The maximum PMN-HOCL production rate for group 1 increased
      from 0.24 nmol/million PMN/min to 0.8 nmol/million PMN/min after treatment with
      antifungal agents (p < 0.01) (Mann-Whitney U test) whereas the PMN-HOCL kinetic
      (rate) curves for group 1 post-treatment and for group 2 were similar (student's
      t-test). CONCLUSIONS: These findings suggest that antifungal treatment improve
      PMN-HOCL production in MOF patients with C. albicans fungaemia and may improve
      the effectiveness in eradicating the organism.

PMID- 12058961
TI  - Bilateral synchronous breast cancer and HER-2/neu overexpression.
AB  - Bilateral synchronous breast cancer appears to have a worse prognosis than
      comparable unilateral breast cancer. HER-2/neu expression in bilateral breast
      cancer has not been reported. The purpose of this study was to review the
      characteristics of patients with bilateral synchronous breast cancer and to
      report the incidence of HER-2/neu overexpression. Between 1984 and 1998, 58
      patients were diagnosed with bilateral synchronous breast cancer (defined as both
      cancers diagnosed within 3 months). The paraffin blocks from both breast
      specimens were available and immunostained in 21 patients. Of 42 breast
      specimens, there were 31 invasive carcinomas and 11 noninvasive carcinomas. Of
      the 21 paired specimens immunostained for HER-2/neu, 11 were invasive cancers in
      both breasts, nine were invasive cancers in one breast and noninvasive cancers in
      the other breast, and one was noninvasive cancers in both breasts. Of the 31
      invasive carcinomas, HER-2/neu was overexpressed (2-3+) in 22 (71%) and negative
      (0-1+) in nine (29%). In contrast, 35 of 101 (34.7%) consecutive unilateral
      invasive breast cancer specimens from our institution overexpressed HER-2/neu.
      The difference in HER-2/neu overexpression between patients with bilateral
      synchronous breast cancer and unilateral breast cancer (22/31 v.s. 35/101) was
      statistically significant (chi square = 11.3, p < 0.001). In cases where both
      breasts had invasive carcinoma, HER-2/neu overexpression could be either in one
      (six patients) or both breasts (four patients). The increased mortality of
      patients with bilateral synchronous breast cancer may be due to the higher
      incidence of HER-21neu overexpression.

PMID- 12058962
TI  - Synergistic interaction between vinorelbine and gamma-linolenic acid in breast
      cancer cells.
AB  - It has been suggested that exogenous unsaturated fatty acids (UFAs) may increase
      the cytotoxic activity of cancer chemotherapeutic agents. We examined how y
      linolenic acid (GLA; 18: 3n-6), the most promising UFA in the treatment of human
      tumors, affects the effectiveness of the lipophilic drug vinorelbine (VNR) on
      human breast carcinoma cell lines. Cells were exposed simultaneously to VNR and
      GLA or sequentially to GLA followed by VNR. Cell viability was determined by MTT
      assay. The increase in VNR-induced cell growth inhibition was measured by
      dividing the IC50 and IC70 values (50 and 70% inhibitory concentrations,
      respectively) that were obtained when the cells were exposed to VNR alone with
      those with VNR plus GLA. We found that GLA enhanced in a dose-dependent manner
      the cell growth inhibitory activity of VNR on MCF-7 cells (up to 9-fold). As GLA
      by itself showed anti-proliferative effects, possible GLA-VNR interactions at the
      cellular level were assessed employing the isobologram analysis and the
      combination index (CI) method of Chou-Talalay. Both methods showed an overall
      synergism between GLA and VNR in MCF-7 cells. At a high level of cell kill, the
      synergism was greater when a 24 h GLA pre-exposure or co-exposures were tested.
      Synergy was likewise observed with the GLA-VNR combination in MDA-MB-231, T47D,
      and SK-Br3 breast cancer cells. In all cell lines, the synergism was independent
      of the treatment schedule and the exposure time. Under conditions inhibiting
      lipid peroxidation using Vitamin E (dl-alpha-tocopherol), the enhancing effect of
      GLA (an easily oxidizable UFA) on VNR activity was partially abolished. However,
      when Vitamin E was used in combination, a similar synergistic increase in growth
      inhibition was obtained. These latter observations strongly implies that the
      synergistic effects of GLA with VNR are not mediated through a mechanism
      involving a generation of lipoperoxides. For comparison, the effects of other
      UFAs were examined on VNR chemosensitivity: GLA was the most potent at enhancing
      VNR activity, followed by docosahexaenoic acid (22: 6n-3), eicosapentaenoic acid
      (20: 5n-3) and alpha-linolenic acid (18: 3n-3), whereas linoleic acid (18: 2n-6)
      and arachidonic acid (20: 4n-6) did not increase VNR chemosensitivity. Very high
      concentrations of oleic acid (OA; 18:1 n-9), an UFA inversely correlated with
      breast cancer risk, also enhanced VNR effectiveness. Thus, various types of UFAs
      were not equivalent with respect to their actions on VNR effectiveness. In
      conclusion, our results give experimental support to the hypothesis that some
      UFAs can be used as modulators of tumor cell chemosensitivity and provide the
      rationale for in vivo preclinical investigation.

PMID- 12058963
TI  - True positive somatostatin receptor scintigraphy in primary breast cancer
      correlates with expression of sst2A and sst5.
AB  - [111In-DTPA-D-Phe1]-octreotide scintigraphy has been shown to reveal somatostatin
      receptor-positive lesions in the majority of primary breast cancers. We have
      recently developed a panel of somatostatin receptor subtype-specific antibodies
      that effectively stain formalin-fixed, paraffin-embedded breast cancer tissue.
      However, it is uncertain to what extend somatostatin receptors detected during
      immunohistochemical staining represent functional binding sites responsible for
      high tracer uptake during somatostatin receptor scintigraphy. PATIENTS AND
      METHODS: We, therefore, conducted a prospective study in which 23 patients with
      suspected breast tumors were included. All patients received [111In]
      pentetreotide scintigraphy. After surgical removal of the tumor, the somatostatin
      receptor status was determined by immunohistochemistry. RESULTS: Among 20
      pathologically proven malignant tumors (14 ductal and six lobular carcinomas), 13
      (approximately 65%) were scintigraphically visible. Of the 20 primary breast
      cancer specimens analyzed, three tumors (approximately 15%) were positive for
      sst1, nine (approximately 45%) revealed immunoreactive sst2A receptors, eight
      (approximately 40%) showed sst3-like immunoreactivity, and 14 (approximately 70%)
      were positive for sst5. There was an excellent correlation between the outcome of
      somatostatin receptor scintigraphy and expression of sst2A (P = 0.025) as well as
      sst5 (P < 0.001) but not expression of either sst1 (P = 0.343) or sst3 (P =
      0.400). CONCLUSION: Both sst2A and sst5 can be responsible for high tracer uptake
      during [111In]-pentetreotide scintigraphy in primary breast cancer. Thus,
      somatostatin receptor scintigraphy may possibly be of value in the detection of
      proven somatostatin receptor sst2A- and/or sst5-positive lesions in metastatic
      breast cancer.

PMID- 12058964
TI  - Expression of Ets-related transcription factors and matrix metalloproteinase
      genes in human breast cancer cells.
AB  - The expression levels of ets and MMP genes was examined in two breast cancer cell
      lines of differing invasive potential. The more invasive MDA-MB-231 cell line had
      higher levels of Ets-1, Ets-2, PEA3, ERM, Tel, Net, MMP-13 and -14 mRNA than MCF
      7 cells. MMP-1, -3 and -16 mRNAs were expressed equally. TPA stimulated MMP-1, -9
      and TIMP-1 mRNA expression in both cell lines. MMP-2 and MMP-7 mRNAs were not
      detected in either cell line. The Ets-1 protein was only detected in MDA-MB-231
      cells and its level increased following TPA stimulation. TPA induced MMP-9
      activity in MCF-7 cells and increased its activity in MDA-MB-231 cells, however,
      MMP-2 activity was not detected.

PMID- 12058965
TI  - Long-term follow-up of a phase II trial studying a weekly doxorubicin-based
      multiple drug adjuvant therapy for stage II node-positive carcinoma of the
      breast.
AB  - BACKGROUND: Combination chemotherapy improves outcomes in women with breast
      cancer (BC) that involves axillary nodes. This single-arm study aimed to evaluate
      the effectiveness of an intensive doxorubicin-based multidrug regimen as adjuvant
      therapy in women with stage II, node positive breast cancer. PATIENTS AND
      METHODS: Between 7/80 and 8/85, 654 women, aged 25-73, who had a mastectomy for
      stage IIB BC were accrued. Patients with prior RT, chemotherapy, or surgical or
      radiation castration within 1 year of diagnosis were excluded. Treatment
      consisted of: 6 weekly courses of IV cyclophosphamide (C) 400 mg/m2, doxorubicin
      (A) 10 mg/m2, vincristine (V) I mg/m2, fluorouracil (F) 400 mg/m2, and a tapering
      course of prednisone followed by 12 courses of C 400 mg/m2, A 20mg/m2, V 1 mg/m2,
      F 400 mg/m2 given every 2 weeks. Patients with estrogen receptor positive tumors
      received Tamoxifen 10 mg bid between weeks 8 and 30. Treatment did not exceed 8
      months. Median follow-up is 13.1 years. RESULTS: Six hundred thirty six patients
      are eligible. Fewer positive (+) nodes, premenopausal status, and positive
      progesterone receptor status are significantly (p < 0.05) associated with longer
      survival. At 10 years, 61% were relapse-free in the 1-3 +node group compared to
      37 and 21% in the 4-9 and > or = 10 +node groups, respectively (p = 0.0001).
      Relapse-free survival at 10 years is 50% for premenopausal and 45% for
      postmenopausal patients. Severe or life-threatening hematological toxicity was
      seen in 6/630 (< 1%) patients. Four patients had severe (grade 3) neurotoxicity
      which resolved. No cardiac toxicity was observed. CONCLUSION: This adjuvant
      regimen compares favorably to other published adjuvant treatments with similar
      length of follow-up.

PMID- 12058966
TI  - Hysteroscopic assessment of menopausal breast-cancer patients taking tamoxifen;
      there is a bias from the mode of endometrial sampling in estimating endometrial
      morbidity?
AB  - The aim of this study is to evaluate the accuracy of hysteroscopy in detecting
      tamoxifen-associated endometrial morbidity. Ninety-eight menopausal breast cancer
      patients taking tamoxifen underwent hysteroscopy because of an endometrial
      thickness above 4mm measured by Transvaginal Ultrasonography. Thirty-one women
      recorded uterine bleeding while 67 were asymptomatic. Hysteroscopies with
      operative facilities were performed, mainly in out-patient setting. Hysteroscopic
      findings were matched with histopathology derived from various modalities of
      tissue collection as suction-curettage, oriented-streak curettage,
      hysteroscopically-targeted biopsies or polypectomies and hysterectomies. Accuracy
      of hysteroscopy to estimate a normal or abnormal endometrium was calculated.
      Abnormal endometrium was detected in 35 patients (64.5% in symptomatic and 22.3%
      in asymptomatic women, P < 0.001). We found six carcinomas, 18 polyps and 11
      hyperplasias. Hysteroscopy showed sensitivity and specificity of 89.2 and 98.4%,
      respectively. By blind sampling, tissue collection was too scant to give a
      diagnosis in 29. 1% of patients and in 80.5% of patients in whom hysteroscopy
      showed cystic atrophy the pathologist failed to confirm this condition. Moreover,
      eight endometrial polyps (36.3%) detected by hysteroscopy were missed.
      Conversely, by tissue sampling under vision no inadequate specimen was sent to
      the pathologist and all hysteroscopies showing cystic atrophy and polyps were
      pathologically confirmed. From literature data, the detection-rate of endometrial
      pathology in tamoxifen users varies from the lowest to the highest prevalences
      whether blind or hysteroscopically-targeted modalities of tissue sampling were
      used, respectively. Hysteroscopy with targeted sampling appears to be the most
      effective method to assess the endometrial lining. In our experience it is safe,
      well tolerated and it should be considered the reference test to assess a
      thickened endometrium in women under tamoxifen.

PMID- 12058967
TI  - Sensitivity of p53-deficient cells to oxaliplatin and thio-TEPA (N, N', N"
      triethylenethiophosphoramide).
AB  - P53 is known as a determinant of cellular responses to DNA damage, including
      apoptosis, cell cycle arrest, and DNA repair. Its role is most easily understood
      in the context of Burkitt lymphoma and other apoptosis-prone cell types. A number
      of epithelial cancer cell types, by contrast, exhibit a higher threshold for
      apoptosis induction in response to DNA damage. In fact, p53 mediates DNA repair
      and protective responses in the latter cell types, in some cases p53-deficient
      cells being more sensitive to DNA damage, antithetical to the situation in
      Burkitt lymphoma and other apoptosis-prone cell types. Ultraviolet light,
      cisplatin, and nitrogen mustards produce damage that is repaired by a p53
      regulated pathway. Here, we explore the sensitivity of the platinum compound
      oxaliplatin and thio-TEPA (N, N', N", triethylenethiophosphoramide), a cancer
      chemotherapeutic agent that produces largely base damage, in p53-defective cells.
      This work demonstrates that the contribution of p53 temporally correlates with
      DNA repair pathways to produce a resistant phenotype, while the p53-defective
      cells are more sensitive to certain DNA-damaging chemotherapeutic agents.

PMID- 12058968
TI  - Purging of contaminating breast cancer cells from hematopoietic progenitor cell
      preparations using activation enhanced cell death.
AB  - Activation enhanced cell death (AECD) involves stimulating cells with growth or
      activation signals while concurrently blocking calcium influx. In this study, we
      have evaluated the effect of AECD on human breast cancer cells. MCF-7 or MDA-MB
      231 cells treated with Ca2+ influx blockers econazole or ketotifen for 24 h
      underwent a dose-dependent, irreversible loss of viability, and clonogenicity.
      Two-hour treatment of these cells with higher concentrations of the drugs also
      resulted in loss of clonogenicity, but morphological indicators of cell death
      were apparent only after longer incubation. Loss of clonogenicity could be
      enhanced almost 10-fold by co-stimulation of the cells with the agonists EGF or
      bombesin. Econazole was also effective in inducing cell death in multi-drug
      resistant MCF-7adr cells. Human hemopoietic progenitor cell sensitivity to
      econazole or ketotifen was evaluated by colony assay. Under conditions resulting
      in 2.5-3 logs of breast cancer cell loss, 60-70% of hemopoietic progenitors could
      be recovered. We further evaluated the effect of econazole on breast cancer cells
      present in mobilized hemopoietic cells obtained from patients undergoing high
      dose chemotherapy with autologous stem cell support. In six of eight samples
      evaluated, cytokeratin-positive breast cancer cells could be detected by
      immunofluorescence microscopy and colony formation. Breast cancer colonies were
      reduced 60-500-fold or more after exposure to econazole while hemopoietic
      colonies were typically reduced only 2-fold. In all cases, addition of EGF as an
      activator either had no evaluable effect or enhanced breast cancer cell loss. We
      conclude that Ca2+ influx blockade with concurrent EGF stimulation is a promising
      approach for purging breast cancer cells from hemopoietic progenitor cell
      preparations.

PMID- 12058969
TI  - Nuclear medicine imaging for prediction or early assessment of response to
      chemotherapy in patients suffering from breast carcinoma.
AB  - Reliable assays that could assess treatment response more rapidly or even predict
      responsiveness of breast tumours to chemotherapy would be very valuable as they
      would allow for adjustment of ineffective treatment and discontinuation of
      ineffective treatment in an early phase. As with effective cancer therapy,
      changes in tumour physiology, metabolism and proliferation do often precede
      volumetric changes routinely measured by morphological imaging modalities, for
      example, radiography and computerized tomography, assessment of these parameters
      by means of single photon emission computerized tomography (SPECT) or positron
      emission tomography may provide more sensitive and earlier markers of tumour cell
      death or growth inhibition. This paper reviews the available literature on the
      role of SPECT and PET in the measurement and visualisation of breast tumour
      metabolism (glucose utilization and protein synthesis rate), apoptosis induction
      and chemotherapy resistance mechanisms as predictors or early markers of tumour
      response or non-response to chemotherapeutic options in patients suffering from
      breast carcinoma.

PMID- 12058970
TI  - The effect of researchers' focus on interpretation of diversity data.
AB  - The tendency for intercultural researchers to focus primarily on cultural
      differences instead of both differences and similarities may reflect the emphasis
      of current statistical methodology toward cultural distance instead of cultural
      overlap. The authors proposed the cultural similarity index as a way of assessing
      the extent of communalities between 2 groups. The authors (a) analyzed research
      (T. Cox, S. Lobel, & P. L. McLeod, 1991; Y. F. Niemann & J. Dovidio, 1998) that
      placed a primary emphasis on differences, (b) presented alternative insights
      gained from a focus on similarities, and (c) explored the implications of a
      research focus on both cultural differences and similarities.

PMID- 12058971
TI  - The effectiveness of the door-in-the-face compliance strategy on friends and
      strangers.
AB  - The author examined the impact of the door-in-the-face procedure on concerns
      about self-presentation and hypothesized that (a) when a friend made door-in-the
      face requests, the procedure would increase the participant's concern about self
      presentation more than would a single request and (b) when a stranger made door
      in-the-face requests, the procedure would not increase the participant's concern
      about self-presentation more than would a single request. Either friends or
      strangers presented requests to the participants. Half the requests were in a
      door-in-the-face format, and the other half were single requests. After receiving
      the request(s), the participants completed measures of self-presentation concerns
      and compliance with the request. The results supported the hypothesis.

PMID- 12058972
TI  - Effects of conflict resolution training integrated into a high school social
      studies curriculum.
AB  - The authors examined the effectiveness of conflict resolution and peer mediation
      training among California high school students. The authors randomly assigned 2
      of 4 classes to receive 5 weeks of conflict resolution and peer mediation
      training integrated into the required social studies curriculum. The remaining 2
      classes studied the same social studies curriculum for an identical amount of
      time (105 min every other day) without conflict resolution and peer mediation
      training. The authors investigated 2 issues. The 1st was the effectiveness of the
      conflict resolution and peer mediation training. The trained students, compared
      with the untrained students, learned the integrative negotiation and peer
      mediation procedures better, applied the procedures more completely, chose an
      integrative over a distributive approach to negotiation, and developed more
      positive attitudes toward conflict. The 2nd issue was the impact of the training
      program on academic achievement. Integrating conflict resolution and peer
      mediation training into an academic course promoted higher achievement, greater
      long-term retention of the academic learning, and greater transfer of academic
      learning in social studies to language arts.

PMID- 12058973
TI  - Value domains of Turkish adults and university students.
AB  - The authors identified the basic dimensions of contemporary values among Turkish
      university students and adults and explored gender and group (adults vs.
      students) differences in the importance attributed to particular value types. The
      authors administered a composite value survey to 101 students from different
      departments of Middle East Technical University and 101 adults from different
      parts of Ankara. Factor analysis yielded 5 value domains: self-enhancement,
      tradition-religiosity, universalism, benevolence, and normative patterning,
      supporting S. H. Schwartz's (1992) motivational value dimensions. Compared with
      the students, the adults attributed more importance to the tradition-religiosity,
      normative patterning, and benevolence domains. Gender similarities were more
      important than gender differences. The results are discussed with reference to
      the studies of values in the literature and prevalent social change in the social
      structure of Turkish society.

PMID- 12058974
TI  - Stress, health, and reciprocity and sufficiency of social support: the case of
      university students in Japan.
AB  - The authors examined the effects of reciprocity and sufficiency of social support
      on the mental and physical health of 488 Japanese university students with
      different levels of stressors. The questionnaire included items that measured
      support provided for, requested by, requested of, and received from others. It
      also addressed negative affect associated with support relationships, as well as
      the levels of stressors and mental and physical health. The participants' support
      relationships with others were fairly reciprocal. Although being overbenefited
      (i.e., receiving more support than one provides) was related to stronger feelings
      of indebtedness, being underbenefited (i.e., providing more support than one
      receives) was related to stronger feelings of burden. In sum, when the
      participants received less support than they requested and when they provided
      less support than others requested, they tended to become less mentally and
      physically healthy. Reciprocity of support appeared to have both direct and
      buffering effects; however, the effects of sufficient support on health did not
      vary with levels of stressors.

PMID- 12058975
TI  - Identity management strategies in Northern Ireland.
AB  - Social identity theory suggests that individuals and groups use different
      identity management strategies to cope with threatened identities. In October
      1998, the authors developed 5 identity management strategy scales for use in the
      changing political context of Northern Ireland and investigated the relationship
      of perceptions of stability and legitimacy, as well as in-group identification,
      to those strategies. Participants were 209 students of the University of Ulster
      and the Belfast Institute. The results supported the factor structure of the
      identity management strategy scales. Perceptions of stability and legitimacy and
      in-group identification were, however, correlated with some strategies only. That
      finding may indicate that some identity management strategies are related to
      psychological constructs not covered by social identity theory.

PMID- 12058976
TI  - Engaging in distancing tactics among sport fans: effects on self-esteem and
      emotional responses.
AB  - The authors examined the effects of distancing tactics on self-esteem and
      emotions, following a win or loss of one's favorite team. They measured state
      self-esteem and emotional responses of basketball fans as they exited the sport
      arena after their team had won or lost an official game. Half of the fans were
      given the opportunity to increase or decrease their association with the team
      before the measures of self-esteem and emotions; the remaining fans were given
      the opportunity after the measures. The fans tended to associate more with the
      team after team success than after team failure. In addition, self-esteem and
      positive emotions were higher, and negative emotions lower, when measured after,
      rather than before, the opportunity to increase or decrease association with the
      team. Those effects were more pronounced among high-team-identification fans than
      among low-team-identification fans. The results suggest a distinction between the
      short- and long-term effects of game outcome on the willingness to associate with
      one's team. In the short term, willingness to associate with the team may
      oscillate in accordance with team performance, even among high-team
      identification fans; in the long term, only high-team-identification fans may
      maintain their allegiance to the team.

PMID- 12058977
TI  - Direct look versus evasive glance and compliance with a request.

PMID- 12058978
TI  - Voting for female candidates: effects of voters' age, ethnicity, and gender.

PMID- 12058979
TI  - Wheat protein composition and properties of wheat glutenin in relation to
      breadmaking functionality.
AB  - The unique breadmaking properties of wheat are generally ascribed to the visco
      elastic properties of its gluten proteins. While monomeric gluten proteins
      (gliadin) show viscous behavior, polymeric gluten proteins (glutenin) are
      elastic. The unique elasticity of glutenin results to a large extent from its
      polymeric nature. Glutenin is a highly heterogeneous mixture of polymers
      consisting of a number of different high- and low-molecular-weight glutenin
      subunits linked by disulfide bonds. Although glutenin obviously is the major
      polymeric protein in wheat, other polymeric proteins occur as well. Their
      importance in breadmaking may be underestimated. Nevertheless, variations in both
      quantity and quality of glutenin strongly determine variations in breadmaking
      performance. Structural features of different classes of glutenin subunits are
      described. Variations in glutenin quality may result from variations in its (1)
      structure, (2) size distribution, and (3) subunit composition. Some hypotheses on
      glutenin structure and current insights into the role of glutenin size
      distribution are evaluated. Finally, different ways in which variation in
      glutenin composition may directly or indirectly (by affecting glutenin structure
      and/or size distribution) influence glutenin quality are discussed.

PMID- 12058980
TI  - Biological properties of olive oil phytochemicals.
AB  - Olive oil is the principal source of fat in the Mediterranean diet, which has
      been associated with a lower incidence of coronary heart disease and certain
      cancers. Extra-virgin olive oil contains a considerable amount of phenolic
      compounds, for example, hydroxytyrosol and oleuropein, that are responsible for
      its peculiar taste and for its high stability. Evidence is accumulating to
      demonstrate that olive oil phenolics are powerful antioxidants, both in vitro and
      in vivo; also, they exert other potent biological activities that could partially
      account for the observed healthful effects of the Mediterranean diet.

PMID- 12058981
TI  - Latent bioactive peptides in milk proteins: proteolytic activation and
      significance in dairy processing.
AB  - After a brief description of the properties of bioactive peptides, the
      proteolytic activation of the bioactive sequences from milk protein precursors is
      discussed. The ability of proteolytic enzymes from various sources, especially
      from lactic acid bacteria, to release bioactive peptides and the physiological
      and biotechnological significance of these peptides in dairy products are
      reviewed.

PMID- 12058982
TI  - Squeezing flow viscometry for nonelastic semiliquid foods--theory and
      applications.
AB  - In most conventional rheometers, notably the coaxial cylinders and capillary
      viscometers, the food specimen is pressed into a narrow gap and its structure is
      altered by uncontrolled shear. Also, most semiliquid foods exhibit slip, and
      consequently the measurements do not always reflect their true rheological
      properties. A feasible solution to these two problems is squeezing flow
      viscometry where the specimen, practically intact and with or without suspended
      particles, is squeezed between parallel plates. The outward flow pattern mainly
      depends on the friction between the fluid and plates or its absence ("lubricated
      squeezing flow"). Among the possible test geometries, the one of constant area
      and changing volume is the most practical for foods. The test can be performed at
      a constant displacement rate using common Universal Testing Machines or under
      constant loads (creep array). The tests output is in the form of a force-height,
      force-time, or height-time relationship, from which several rheological
      parameters can be derived. With the current state of the art, the method can only
      be applied at small displacement rates. Despite the method's crudeness, its
      results are remarkably reproducible and sensitive to textural differences among
      semiliquid food products. The flow patterns observed in foods do not always
      follow the predictions of rheological models originally developed for polymer
      melts because of the foods' unique microstructures. The implications of these
      discrepancies and the role that artifacts may play are evaluated in light of
      theoretical and practical considerations. The use of squeezing flow viscometry to
      quantify rheological changes that occur during a product's handling and to
      determine whether they are perceived sensorily is suggested.

PMID- 12058983
TI  - Foods and health promotion: the case for cranberry.

PMID- 12058984
TI  - Fighting infectious diseases with inhibitors of microbial adhesion to host
      tissues.
AB  - The majority of infectious diseases are initiated by the adhesion of pathogenic
      organisms to the tissues of the host. In many cases this adhesion is mediated by
      lectins present on the surface of the infectious organism that bind to
      complementary carbohydrates on the surface of the host tissues. Soluble
      carbohydrates recognized by the bacterial lectins block the adhesion of the
      bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown
      to protect against experimental infection by lectin-carrying bacteria of
      different mammals, such as mice, rabbits, calves, and monkeys. Agents other than
      carbohydrates also block adhesion, as demonstrated with cranberry juice as well
      as with low and high molecular weight preparations isolated from the juice. Both
      kinds of preparation inhibited the adhesion in vitro of Escherichia coli to
      different animal cells. In addition, the high molecular weight material acted
      similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells,
      and on the coaggregation of oral bacteria. Furthermore, in limited clinical
      studies regular drinking of cranberry juice had a significant preventive effect
      on bacteriuria, and the high molecular weight constituent of the juices was also
      effective in decreasing the salivary level of Streptococus mutans, the major
      cause of tooth decay. Because the inhibitors of adhesion examined are not
      bactericidal, the selection of resistant inhibitor strains is unlikely to occur.
      Together, these findings may lead to new therapeutic strategies that are in dire
      need because of the world-wide increase in antibiotic resistant bacteria.

PMID- 12058985
TI  - Cranberry proanthocyanidins and the maintenance of urinary tract health.
AB  - One of the major health benefits attributed to the ingestion of cranberry juice
      is the maintenance of urinary tract health. Traditionally, the juice was thought
      to cause acidification of the urine resulting in a bacteriostatic effect.
      However, recent research has demonstrated that a bacterial antiadhesion mechanism
      is responsible. Proanthocyanidins with unique molecular structures have been
      isolated from cranberry fruit that exhibit potent bacterial antiadhesion
      activity. Little is known about the bioavailability and structure-activity
      relationships of cranberry proanthocyanidins. Data on how certain structural
      features of the molecules can influence bioactivity and bioavailability are
      reviewed.

PMID- 12058986
TI  - Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high
      molecular-weight constituent of cranberry juice.
AB  - A high-molecular-weight constituent of cranberry juice has been found to inhibit
      the sialyllactose specific adhesion of Helicobacter pylori strains to immobilized
      human mucus, erythrocytes, and cultured gastric epithelial cells. Different
      isolates of H. pylori differ in their affinity to the cranberry juice
      constituent. Cranberry juice may also inhibit adhesion of bacteria to the stomach
      in vivo, and may prove useful for the prevention of stomach ulcer that is caused
      by H. pylori.

PMID- 12058987
TI  - Inhibitory effect of a high-molecular-weight constituent of cranberry on adhesion
      of oral bacteria.
AB  - A high-molecular-weight nondialysable material (NDM) isolated from cranberry
      juice at a concentration of 0.6 to 2.5 mg/ml dissociated coaggregates formed by
      many intergeneric oral bacteria. A lower concentration of NDM was required to
      inhibit formation of such coaggregates. NDM acted preferentially on pairs of oral
      bacteria in which one or both members are Gram-negative anaerobes. The high
      molecular-weight material from blueberry also inhibited the coaggregation,
      although its activity was weaker, whereas such materials obtained from other
      fruits were inactive. Saliva did not interfere with the ability of NDM to inhibit
      coaggregation. A preliminary clinical trial showed that NDM reduces S. mutans
      counts in saliva. The antiadhesion activity of cranberry juice has a potential
      for altering the oral microbial flora resulting in improved oral hygiene.

PMID- 12058988
TI  - The role of cranberry and probiotics in intestinal and urogenital tract health.
AB  - Several forces are driving an expanded use of nutraceuticals, particularly
      functional foods and probiotics, as instruments of the restoration and
      maintenance of well-being. These include consumer desire to use natural rather
      than pharmaceutical products, the mounting scientific evidence that shows
      efficacy of certain nutraceutical products, and the increasing cost and continued
      failure of drugs to cure or prevent disease. There is now a strong scientific
      basis for use of cranberries to reduce the risk of E. coli adhesion to bladder
      cells and the onset of urinary tract infection. There is also a mechanistic basis
      and clinical support for use of Lactobacillus strains such as L. rhamnosus GR-1
      and L. fermentum RC-14 to colonize the intestine and vagina and reduce the risk
      of intestinal and urogenital infections. For such alternative approaches to be
      successful, scientific rigor must be backed by public education and physician
      acceptance. Given the emergence of virulent and multidrug-resistant pathogens,
      time is not on our side.

PMID- 12058990
TI  - Ethical stresses in uremia therapy: the worst is yet to come.

PMID- 12058989
TI  - Cranberry flavonoids, atherosclerosis and cardiovascular health.
AB  - Atherosclerosis is the deposition of plaques containing cholesterol and lipids in
      arterial walls. Atherosclerosis causes cardiovascular disease that lead to heart
      attacks and stroke. Mortality from these diseases is the leading cause of death
      in the U.S. Atherogenisis starts with the uptake of oxidized LDL by endothelial
      macrophages, the accumulation of foam cells in the intima of the artery and the
      formation of fatty streaks. Research indicates that consumption of flavonoids in
      foods and beverages may decrease the risk of atherosclerosis. In vitro and in
      vivo experiments with flavonoids demonstrate that flavonoids are dietary
      antioxidants and inhibit LDL oxidation, inhibit platelet aggregation and
      adhesion, inhibit enzymes involved in lipid and lipoprotein metabolism that
      affect the immune response to oxidized LDL and their uptake by endothelial
      macrophages, may induce endothelium-dependent vassorelaxation, and may increase
      reverse cholesterol transport and decrease total and LDL cholesterol. Cranberries
      contain both hydroxycinnamic acids and flavonoids. The cranberry flavonoids
      belong to three groups: anthocyanins, flavonols, and proanthocyanidins. This
      article reviews the literature on the effects of flavonoids on atherosclerosis
      with an emphasis on the potential effects of the flavonols and proanthocyanidins
      in cranberries.

PMID- 12058991
TI  - Solving the organ shortage: potential strategies and the likelihood of success.
AB  - The discrepancy between the demand and supply of organs for clinical
      transplantation remains a major problem. The current incidence of end-stage renal
      disease results in a patient population that doubles every decade. However, there
      have been no advancements in developing a comparable increase in the number of
      available allografts. There are three potential approaches to solving the
      shortage. In the near-term, the development of technology to access the pool of
      warm ischemically damaged organs may represent a solution. To achieve this goal,
      it will be necessary to develop technology that mimics the physiologic processes
      of wound repair. Alternatively, it has been proposed that an increased supply of
      organs can be developed with xenografts. To make xenotransplantation a clinical
      reality, it will be necessary to overcome the barriers that exist in nature
      between the species. Recent work in the area of stem cell research has provided
      evidence supporting the potential of generating biohybrid organs. A major
      undertaking of this emerging field will be to develop the ability to define and
      control the differentiation processes involved in organ specificity. The
      following is a review of the current status and relative issues involved with
      these three potential approaches to solving the organ shortage.

PMID- 12058992
TI  - Pediatric circulatory support systems.
AB  - Ventricular assist devices (VADs) are a valid option for long term circulatory
      support in pediatric patients with postoperative myocardial failure or
      debilitating heart defects. Most clinical experience to date has involved the
      short-term support of patients weighing 6 kg and larger. For cases of VAD
      implementation in pediatric patients, the assist device showed tremendous promise
      in reversing cardiac failure and providing adequate support as a bridge to
      cardiac transplantation. The Medos-HIA system, Berlin Heart, Medtronic Bio
      Medicus Pump, Abiomed BVS 5000, Toyobo-Zeon pumps, and Hemopumps have proven
      successful for short-term circulatory support for the pediatric population. The
      Jarvik 2000 and Pierce-Donachy pediatric system further demonstrate the potential
      to be used for pediatric circulatory support. The clinical and experimental
      success of these support systems provide encouragement to believe that long-term
      support is possible.

PMID- 12058993
TI  - In vivo studies of the MagScrew total artificial heart in calves.
AB  - The purpose of this study was to evaluate the in vivo pump performance of our
      total artificial heart (TAH), the "MagScrew TAH." The TAH consists of a blood
      pump and control logic developed at the Cleveland Clinic and the MagScrew
      actuator and electronic control system developed by Foster-Miller Technologies,
      Inc. (Albany, NY). MagScrew TAH implantation was performed in two calves. Study
      durations were 50 and 5 days. The causes of termination were prosthetic valve
      endocarditis in one case and cable failure in the other. Mean left pump flow
      ranged from 8.0 to 9.7 L/min, with left atrial pressure of 3.0 to 16.0 mm Hg.
      Preload sensitivity of the MagScrew TAH demonstrated a Frank-Starling response to
      preload in automatic mode. The relationship between right and left atrial
      pressure was well balanced. Mean arterial pressure and mean pulmonary artery
      pressure were maintained within physiologic ranges over study duration. There
      were no signs of bleeding, hemolysis, or organ failure. The MagScrew TAH showed
      physiologic pump performance, and hemodynamics were well maintained without any
      organ failure. Further development testing will bring the MagScrew TAH to the
      point of preclinical readiness testing.

PMID- 12058994
TI  - Plasma versus whole blood perfusion in a bioartificial liver assist device.
AB  - The ramifications of using whole blood or plasma for perfusion off an hepatocyte
      containing bioartificial liver bioreactor in which the hepatocytes are separated
      by a membrane or other physical barrier from the perfusate stream on the rate of
      change of patient blood concentrations are explored through dynamic modeling of
      whole blood perfusion as a two compartment system (patient tissue and blood
      compartments), and plasma perfusion as a three compartment system (patient tissue
      and blood compartments, and a plasma reservoir). The whole blood perfusion model
      is described by three dimensionless parameters: the Damkohler number, Da, which
      represents the ratio of the rate of conversion by the bioreactor to the rate of
      perfusion; kappa, which represents the ratio of the rate of internal
      reequilibration between the tissue and blood compartments and the rate of
      perfusion; and Vtb, the tissue/blood volume ratio. The plasma perfusion model has
      three additional dimensionless parameters: f, the fraction of plasma withdrawn
      from the blood in a plasma separator; alpha, the ratio of the plasma perfusion
      rate in the bioreactor to the blood draw rate; and Vbr, the blood/plasma
      reservoir volume ratio. Within the physiologic range of parameters, the rate of
      reduction in blood concentration in both the whole blood-perfused and plasma
      perfused systems are sensitive to Damkohler number up to Da approximately 2.
      Neither system is sensitive to variations in kappa, and the plasma perfusion
      system has little sensitivity to alpha. Given bioreactors of equivalent activity,
      a greater rate of blood concentration reduction and lower endpoint blood
      concentration at equivalent perfusion times will be achieved with whole blood
      perfusion. There are two physical reasons for this. The first is that the plasma
      perfused system is only processing a fraction, f, of the blood compared with the
      whole blood perfusion system. The second reason is that, although the blood
      perfused system is limited by overall bioreactor performance, the plasma-perfused
      system is mass transfer limited to the rate of blood concentration dilution into
      the plasma reservoir rather than limited by the overall bioreactor performance.

PMID- 12058995
TI  - A new approach to completely autologous cardiovascular tissue in humans.
AB  - In cardiovascular tissue engineering, synthetic or biologic scaffolds serve as
      templates for tissue development. Currently used scaffolds showing toxic
      degradation and immunogenic reactions are still far from ideal. We present a new
      alternative method to develop completely autologous human tissue without using
      any scaffold materials. Human vascular cells of arterial and venous origin were
      cultured to form cell sheets over a 4 week period under standard conditions.
      Thereafter, cell sheets of each origin were folded and cultured in a newly
      developed frame device for an additional 4 weeks. Controls remained under
      standard culture conditions. Tissue development was evaluated by morphology and
      biochemical assays. The formation of multilayered cell sheets and production of
      extracellular matrix were observed in all groups. Folded and framed neo-tissue
      showed a solid structure, with increased matrix formation and tissue organization
      when compared with the control groups. DNA content indicated significantly lower
      cell proliferation, and hydroxyproline assay indicated significantly higher
      collagen content in the framed cell sheets. We present a new approach to the
      engineering of cardiovascular tissue without the use of biodegradable scaffold
      material. Three-dimensional, completely autologous human tissue may be developed
      on the basis of this structure, thus avoiding scaffold induced toxic degradation
      or inflammatory reaction.

PMID- 12058996
TI  - A pressure controller of selective cerebral perfusion with single centrifugal
      pump.
AB  - We are developing an original nonroller extracorporeal circulation system
      (NRECC). However, this NRECC could not perform selective cerebral perfusion
      (SCP). Therefore, we added cerebral perfusion lines and an automatic pressure
      controller to the system. The purpose of this study was to evaluate the stability
      and response of the pressure controller for the SCP in simulated clinical
      circulation. The NRECC consists of a centrifugal pump, four isolated vacuum
      suction lines and a conventional module. The SCP line branches from the main
      perfusion tubing and divides into three lines. Cerebral perfusion is regulated by
      a pressure controller, which is composed of an actuator, a pressure transducer,
      and a personal computer. The mock circuit was primed with normal saline, and the
      actual SCP pressure and flow were measured when the target pressure settled at
      60, 80, and 100 mm Hg. The main perfusion flow was maintained at 4 L/min and the
      main perfusion pressure was altered from 120 to 300 mm Hg. The pressure and flow
      data were recorded. The SCP pressure was maintained within +/-1.47 mm Hg when the
      set pressure was 80 mm Hg. Fluctuation of flow in the SCP line was within the
      range of +/-2.8%. The time needed to reach the steady state pressure was 8+/-1
      seconds when the initial setting of the roller occluder was full-open, and it
      took only 3+/-1 seconds to reach the next initial set pressure. We have developed
      the NRECC-SCP system. The SCP pressure is stable and quickly reaches steady state
      via the pressure controller. This system is useful for extracorporeal circulation
      during aortic arch operation.

PMID- 12058997
TI  - Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion
      in septic patients with trauma.
AB  - We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is
      increased in septic patients with trauma and whether polymyxin B immobilized
      fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18
      trauma patients with sepsis, and 10 healthy controls were included in this study.
      The 18 trauma patients with sepsis were randomly assigned to one of two groups,
      PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine
      were measured before and after treatment. Plasma endotoxin levels were determined
      by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours,
      at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2+/-2.2
      mg/mmol) in comparison to that in the healthy controls (1.0+/-0.6 mg/mmol, p <
      0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6+/-4.8
      mg/mmol) was significantly greater than that before sepsis (5.5+/-2.3 mg/mmol, p
      < 0.01). There was a significant correlation between plasma endotoxin levels and
      MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0+/-5.0
      mg/mmol to 4.2+/-1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels
      were also reduced from 34.5+/-18.5 pg/ml to 10.8+/-6.6 pg/ml (p < 0.01). Neither
      MACR nor plasma endotoxin levels were affected by conventional treatment,
      however. In summary, trauma patients with sepsis appear to show increased MACR,
      and PMX-F therapy may be effective for attenuating the increase in MACR.

PMID- 12058998
TI  - Cleveland clinic CorAide blood pump circulatory support without anticoagulation.
AB  - The Cleveland Clinic CorAide left ventricular assist system consists of a
      permanently implantable centrifugal pump in which the rotating assembly is
      completely suspended and noncontacting. A series of chronic animal in vivo
      studies were conducted to evaluate the biologic effects of CorAide circulatory
      support without the use of anticoagulation therapy. The CorAide pump was
      implanted in six calves (five calves for 21 to 32 days and one calf for 95 days).
      The first five calves received intravenous heparin during the early postoperative
      periods (2-7 days). Heparin administration was then discontinued and no other
      anticoagulant drugs were used for the duration of the experiments. The last calf
      did not receive any anticoagulant except for a bolus dose of heparin (200 U/kg)
      during surgery. Hemodynamics were stable in all six calves, with a mean pump flow
      of 5.6+/-1.2 L/min and mean arterial pressure of 100+/-4 mm Hg. The blood pump
      surfaces were clean of thrombus in all six calves. Significant findings at
      autopsy were limited to one case of renal infarction. There was no incidence of
      mechanical failure, bleeding, or device infection. The CorAide pump can be safely
      run with minimal or no anticoagulant therapy.

PMID- 12058999
TI  - CardioClasp: a new passive device to reshape cardiac enlargement.
AB  - In dilated heart failure, geometric distortions place an extra load on the
      myocardial cells. If this extra burden can be eliminated, the myocardial wall
      stress would decrease leading to improved systolic ventricular performance. In a
      dilated heart failure model, we wanted to see whether the CardioClasp (which uses
      two indenting bars to reshape the left ventricle [LV] as two widely communicating
      "lobes" of reduced radius) could improve systolic performance by passively
      reshaping the LV and reducing the wall stress. In mongrel dogs (n = 7; 25-27 kg),
      rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated
      heart failure. After 4 weeks, LV performance was evaluated at baseline and with
      the CardioClasp by measuring LV end-diastolic and peak LV systolic pressure, LV
      +dP/dt, LV -dP/ dt, and cardiac output. With the Clasp on, LV wall stress was
      reduced to 58.6+/-3.5 from 108.3+/-8.2 g/cm2. The fractional area of contraction
      (FAC) with the Clasp on (28.4+/-4.4) was significantly increased (p < 0.05) from
      baseline (20.8+/-4.6) and consistent with improved systolic performance. Cardiac
      output, LV peak systolic and end-diastolic pressures, and regional myocardial
      blood flow were unaltered. The Clasp was able to acutely reshape the left
      ventricle, while preserving the contractile mass, and reduced the tension on the
      myocardial cells and increased the fractional area of contraction without
      decreasing the systolic blood pressure.

PMID- 12059000
TI  - Development of a new disposable pulsatile pump for cardiopulmonary bypass:
      computational fluid-dynamic design and in vitro tests.
AB  - A newly conceived blood pump for pulsatile cardiopulmonary bypass (CPB) is
      presented. The new device's main design features (fully disposable pumping head
      with ring shaped valves) were intended to overcome the factors that today limit
      the use of pulsatile blood pumps, i.e., the complexity and costs of devices. The
      pump was designed and analyzed by means of three-dimensional computational
      models, including solid computer assisted design of the pumping head and
      computational fluid-dynamic (CFD) analyses of the fluid domain and of its
      interaction with deformable components. A prototype of the device, integrated
      with the venous reservoir, was built to perform hydraulic in vitro tests with
      aims of both validating CFD results and verifying the new device's pumping
      behavior. Functional evaluation of the pump was carried out by using the device
      in a model circuit made with standard CPB components plus a mock hydraulic bench
      representing an adult patient's systemic circulation. A roller pump used in
      pulsatile mode (RP-PM) was used for comparison. At a 5 L/min flow rate, the
      pulsatile hydraulic power (<Wpuls>) delivered to the patient was approximately 15
      mW for the RP-PM. The new pump proved to be able to deliver <Wpuls> up to 40 mW,
      thus providing a more physiological condition, closer to the <Wpuls> delivered by
      the natural heart (90-140 mW).

PMID- 12059001
TI  - Device based left ventricular shape change: validation of conductance technology
      in shape changed hearts.
AB  - We have reported that device based left ventricular (LV) shape change,
      accomplished by Myosplint, improved LV systolic function by three-dimensional
      echocardiography (3-D echo). However, evaluation of this device using the
      pressure-volume relationship is still important. This study was conducted to
      validate the use of conductance technology for this evaluation in shape-changed
      hearts. An ex vivo study using excised ovine hearts (n = 11) and an in vivo study
      using a canine pacing-induced heart failure model (n = 11) were performed. Three
      Myosplints were implanted. Before and after the shape changes, volumes measured
      by a conductance catheter were compared with volumes measured by the amount of
      saline in the ex vivo study or by 3-D echo in the in vivo study. The conductance
      volumes were linearly correlated with the saline volumes (r2 = 0.961+/-0.046; p <
      0.0001) in the ex vivo study and with 3-D echo volumes (r2 = 0.757+/-0.220; p <
      0.0001) in the in vivo study. The conductance volumes were linearly correlated
      with LV volumes even in the shape-changed hearts. This technology can be used to
      evaluate pressure-volume loops in the shape-changed hearts as long as the
      conductance volume is calibrated by a reliable method.

PMID- 12059002
TI  - Modeling and control of a brushless DC axial flow ventricular assist device.
AB  - This article presents an integrated model of the human circulatory system that
      incorporates circulatory support by a brushless DC axial flow ventricular assist
      device (VAD), and a feedback VAD controller designed to maintain physiologically
      sufficient perfusion. The developed integrated model combines a network type
      model of the circulatory system with a nonlinear dynamic model of the brushless
      DC pump We show that maintaining a reference differential pressure between the
      left ventricle and aorta leads to adequate perfusion for different pathologic
      cases, ranging from normal heart to left heart asystole, and widely varying
      physical activity scenarios from rest to exercise.

PMID- 12059003
TI  - Toward a durable impeller pump with mechanical bearings.
AB  - Our former work demonstrated that our impeller pump could support the circulation
      of experimental animals for several months without harm to blood elements or
      organ function. The termination of the experiments was mostly related to wear of
      the mechanical bearing and thrombosis along the bearing. To solve the bearing
      problem, we investigated a magnetic bearing in our lab, which resulted in some
      new problems, such as complicated design and control, considerable energy
      consumption, and lesser reliability. Progress in developing an impeller pump for
      long-term application has recently been achieved. Instead of using a sliding
      bearing system, we devised a rolling bearing system. Its service life is more
      than 10 years because of a wearproof roller made of ultra high molecular weight
      polythene. To avoid thrombus formation, we introduced a special purge system to
      the bearing, allowing the saline with heparin to be infused through the bearing
      into the pump. The bearing, therefore, keeps working in the saline, and no
      thrombus will be formed. Animal experiments demonstrated that a 30 ml fluid
      infusion per hour is enough to prevent thrombus formation. With these
      improvements, the impeller pump has continuously run for 8 months, and no bearing
      wear can be measured. The device, weighing 150 g, is fully implantable, consumes
      approximately 9.6 watts, and delivers a 9L/min blood flow against a 120 mm Hg
      mean pressure and reaches a highest total efficiency of 24.7% for the motor
      (including the controller) and pump. The system can produce both pulsatile and
      nonpulsatile flow according to requirements.

PMID- 12059004
TI  - Failure mode and effects analysis as an informed consent tool for investigational
      cardiothoracic devices.
AB  - The informed consent process is one of the most critical segments of any device
      clinical trial. Informed consent requires that patients be provided with ample
      and accurate information about the risks and benefits of trial participation in a
      manner that respects their learning ability. Knowing this, the dilemma for
      clinical investigators lies in identifying the risks without having had clinical
      experience with the device in question. It is offered that the device
      manufacturer's FMEA (failure mode and effects analysis) document can be a
      valuable aid in determining the potential clinical risks of investigational
      devices, and thus should be available to clinical investigators for their
      preparation of informed consent documentation.

PMID- 12059005
TI  - Vasomotion model explanation for urea rebound.
AB  - Urea rebound after hemodialysis is generally attributed to urea entering the
      circulation from poorly perfused tissue and/or entering from regions with low
      membrane permeability for urea. Another explanation for rebound is based on
      disorders in the microcirculation, connected with the phenomenon of vasomotion,
      i.e., cyclic opening and closing of microvessels. The purpose of the following
      mathematical model is to explain observed urea rebound by the vasomotion
      phenomenon. The significance of vasomotion is related to the fact that a
      significant fraction, up to 80-95%, of all microvessels are closed while others
      are being perfused. The rate with which open microvessels "migrate" through the
      tissue determines quality of perfusion. A stochastic scheme for describing
      vasomotion is developed. Probabilities to change the state of microvessels are
      defined as follows: alpha = probability to be open and remain open; beta = to be
      open and become closed; v = to be closed and remain closed; mu = to be closed and
      become open. The activity of vasomotion is defined by the rate of vasomotion, R,
      R = beta + mu, and can be measured using a curve of urea concentration.

PMID- 12059006
TI  - Effects of reuse and bleach/formaldehyde reprocessing on polysulfone and
      polyamide hemodialyzers.
AB  - The surface features, morphology, and blood interactions of fibers from pristine,
      bleach/formaldehyde reprocessed, and reused Fresenius Polysulfone High Flux
      (Hemoflow F80B) hemodialyzers and Gambro Polyflux 21S Polyamide hemodialyzers
      have been studied. SEM images of fibers from both hemodialyzer types revealed a
      dense skin layer on the inner surface and a relatively thick porous layer on the
      outer surface. The 21S polyamide support layer consisted of interconnected highly
      porous structures. Environmental scanning electron microscopy and atomic force
      microscopy images of both membrane types showed alterations in morphology due to
      reprocessing and reuse; however the changes were more marked for the 21S
      polyamide dialyzers. Fluorescence microscopy images showed only minimal
      fluorescence associated with the fibers after patient use and reprocessing,
      suggesting that blood derived deposits were removed by processing. The protein
      layers formed on pristine and reused hemodialyzer membranes during clinical use
      were studied using SDS-PAGE and immunoblotting. Before bleach/formaldehyde
      treatment, protein layers of considerable amount and complexity were found on the
      blood side of singly and multiply used dialyzers. Proteins adsorbed on the
      dialysate side were predominantly in the molecular mass region below 30 kDa.
      However, some higher molecular mass proteins were detected on the dialysate side
      of the 21 S polyamide dialyzers. Very little protein was detected on dialyzers
      that were treated with bleach/formaldehyde after dialysis, regardless of whether
      they had been used/reprocessed once or 12 times.

PMID- 12059007
TI  - Biofeedback regulation of ultrafiltration and dialysate conductivity for the
      prevention of hypotension during hemodialysis.
AB  - Intradialytic hypotension remains a frequent complication of dialysis, occurring
      in up to 33% of patients. We tested a fully integrated biofeedback system (the
      Hemocontrol system) that monitors and regulates blood volume contraction during
      hemodialysis. Seven hypotension prone patients were selected for the study. We
      conducted a prospective crossover study alternating dialysis sessions using the
      blood volume regulation system and standard dialysis sessions. Event free
      sessions were defined as dialysis sessions not requiring any therapeutic
      intervention for hypotension related signs or symptoms. There was a significant
      improvement in the number of event free sessions with blood volume regulation
      compared with standard dialysis (50.8% of sessions vs. 29.2%; p < 0.01).
      Percentages of event free sessions and mean postdialysis systolic blood pressure
      improved progressively over the course of the study, indicating improved
      hemodynamic stability over the study period. Therefore, the use of a biofeedback
      system to monitor and regulate blood volume during dialysis was helpful in
      restoring cardiovascular stability in a population of hypotension prone
      hemodialysis patients. Further studies are needed to confirm these preliminary
      results and to establish the role of blood volume regulation systems in reducing
      the incidence of hypotension during hemodialysis.

PMID- 12059008
TI  - Effect of reversal of catheter ports on recirculation: comparison of the PermCath
      with Tesio Twin Catheter.
AB  - To study the effect of the reversal of the blood ports on blood flow rate (QB),
      percentage recirculation, and blood urea nitrogen (BUN) clearance, we compared 12
      well functioning chronic hemodialysis catheters (7 PermCaths and 5 Tesio Twin
      Catheters) in both standard and reversed blood flow setups. The reversal of
      PermCath ports caused no change in the QB (307+/-20 ml/min vs. 314+/-9 ml/min,
      standard vs. reversed hook-up, respectively), but a significant increase in
      percentage recirculation (2.5+/-1.8% vs. 12+/-4.6%, standard vs. reversed hook
      up, respectively, p = 0.02). Reversal of the Tesio Twin Catheter ports caused a
      significant decline in QB (296+/-13 ml/min vs. 250+/-16 ml/min, standard vs.
      reversed hook-up, respectively, p = 0.02), but no significant change in
      percentage recirculation (2.8+/-1.4% vs. 3.8+/-2.5%, standard vs. reversed hook
      up, respectively, p = not significant). Reversal of the ports caused no
      significant change in BUN clearance with the PermCath (264+/-18 ml/min vs. 257+/
      17, standard vs. reversed hook-up, respectively, p = 0.8), but a significant
      decline in BUN clearance with the Tesio Twin Catheter (247+/-11 ml/min vs. 216+/
      13.5 ml/min, standard vs. reversed hook-up, respectively, p = 0.015). In
      conclusion, our results suggest that reversed hook-up of a well functioning Tesio
      Twin Catheter is associated with a significant decline in QB and BUN clearance,
      but no change in percentage recirculation; however, inadvertent reversed hook-up
      of a well functioning PermCath can lead to a considerable increase in percentage
      recirculation but no change in QB or BUN clearance.

PMID- 12059009
TI  - Improvement of cardiac function by dry weight optimization based on interdialysis
      inferior vena caval diameter.
AB  - In hemodialysis (HD) patients, the diameter of the inferior vena cava (IVC)
      serves for evaluation of the amount of body fluid. IVC measurement is usually
      performed immediately before and/or after an HD session. In the present study, we
      examined the validity of IVC diameter in the interdialysis period (interdialytic
      IVC) for dry weight (DW) optimization. In 100 HD patients, interdialytic IVC was
      measured ultrasonographically. The average maximum IVC diameter during quiet
      expiration (IVCe) was 14.2+/-3.8 mm. In 32 patients with volume dependent
      hypertension, the interdialytic IVCe was > 16 mm in 29 of 32. Thus, we defined an
      interdialytic IVCe > 16 mm as a hypervolemic state. Next, by screening 306 HD
      patients ultrasonographically, 31 patients with left ventricular volume overload
      were chosen based on criteria of an interdialytic IVCe > 16 mm, together with a
      left ventricular ejection fraction (EF) < 55%. After the DW was lowered to obtain
      an interdialytic IVCe < 16 mm, 25 of the 31 patients had a significant increase
      in EF, decrease in diastolic left ventricular dimension, and amelioration of
      hypertension. In conclusion, interdialytic IVCe is considered to be a useful
      parameter for DW optimization. In hypervolemic patients with IVCe > 16 mm,
      reduction in DW is expected to improve volume overload and cardiac function.

PMID- 12059010
TI  - Continuous monitoring of plasma, interstitial, and intracellular fluid volumes in
      dialyzed patients by bioimpedance and hematocrit measurements.
AB  - Bioimpedance spectroscopy (BIS) permits evaluation of extra- and intracellular
      fluid volumes in patients. We wished to examine whether this technique, used in
      combination with hematocrit measurement, can reliably monitor fluid transfers
      during dialysis. Ankle to wrist BIS measurements were collected during 21
      dialysis runs while hematocrit was continuously monitored in the blood line by an
      optical device. Extracellular (ECW) and intracellular (ICW) water volumes were
      calculated using Hanai's electrical model of suspensions. Plasma volume
      variations were calculated from hematocrit, and changes in interstitial volume
      were calculated as the difference between ECW and plasma volume changes. Because
      accuracy of ICW was too low, changes in ICW were calculated as the difference
      between ultrafiltered volume and ECW changes. Total body water (TBW) volumes
      calculated pre- and postdialysis were, respectively, 3.25+/-3.2 and 1.95+/-2.5
      liters lower on average than TBW given by Watson et al.'s correlation. Average
      decreases in fluid compartments expressed as percentage of ultrafiltered volume
      were as follows: plasma, 18%; interstitial, 28%, and ICW, 54%. When the
      ultrafiltered volume was increased in a patient in successive runs, the relative
      contributions of ICW and interstitial fluid were augmented so as to reduce the
      relative drop in plasma volume.

PMID- 12059011
TI  - Plasma-sprayed calcium phosphate particles with high bioactivity and their use in
      bioactive scaffolds.
AB  - Highly crystalline feedstock hydroxyapatite (HA) particles with irregular shapes
      were spheroidized by plasma spraying them onto the surface of ice blocks or into
      water. The spherical Ca-P particles thus produced contained various amounts of
      the amorphous phase which were controlled by the stand-off distance between the
      spray nozzle and the surface of ice blocks or waiter. The smooth surface
      morphology without cracks of spherical Ca-P particles indicated that there were
      very low thermal stresses in these particles. Plasma-sprayed Ca-P particles were
      highly bioactive due to their amorphous component and hence quickly induced the
      formation of bone-like apatite on their surfaces after they were immersed in an
      acellular simulated body fluid at 36.5 C. Bone-like apatite nucleated on
      dissolved surface (due to the amorphous phase) of individual Ca-P particles and
      grew to coalesce between neighboring Ca-P particles thus forming an integrated
      apatite plate. Bioactive and biodegradable composite scaffolds were produced by
      incorporating plasma-spray ed Ca-P particles into a degradable polymer. In vitro
      experiments showed that plasma-sprayed Ca-P particles enhanced the formation of
      bone-like apatite on the pore surface of Ca-P/PLLA composite scaffolds.

PMID- 12059012
TI  - Production and evaluation of biodegradable composites based on PHB-PHV copolymer.
AB  - In recent years, emphasis in biomaterials engineering has moved from materials
      that remain stable in the biological environment to materials that can degrade in
      the human body. Biodegradable materials are designed to degrade gradually and be
      replaced eventually by newly formed tissue in the body. In this investigation,
      two particulate bioactive ceramics, i.e., hydroxyapatite (HA) and tricalcium
      phosphate (TCP), were incorporated into polyhydroxybutyrate-polyhydroxyvalerate
      (PHB-PHV), which is a biodegradable copolymer. to produce new biomaterials for
      potential medical applications. All raw materials were commercially available and
      they were characterised prior to composite production. HA/PHB-PHV and TCP/PHB-PHV
      composites containiing up to 30 vol% of the bioceramics were produced through an
      established procedure. Compounded and compression moulded materials were
      evaluated using various techniques including thermogravimatric analysis, scanning
      electron microscopy, differential scanning calorimetry and dynamic mechanical
      analysis. The results showed that intended compositions of composites had been
      achieved and bioceramic particles were well distributed in the polymer. The
      degradation temperature of PHB-PHV was significantly reduced by the incorporation
      of bioceramics, while the melting temperature was slightly affected by the
      addition of bioceramics. The crystallinity of PHB-PHV was also varied with the
      presence of HA or TCP particles. The storage modulus and loss modulus of the
      composites increased with the increase in HA or TCP content. Composites
      containing the highest percentage of bioceramics exhibited the highest stiffness.
      Preliminary in vitro study indicated enhanced ability of the composites to induce
      the formation of bone-like apatite on their surfaces.

PMID- 12059013
TI  - Properties and biocompatibility of chitosan films modified by blending with PEG.
AB  - Chitosan (beta-1,4-D-glucosamine), a polysaccharide with excellent biological
      properties, has been widely used in biomedical fields, but many barriers still
      exist to its broader usage due to its chemical and physical limitations. Further
      work is needed to improve these properties, but changes of the chemical and
      physical properties will influence its biocompatibility, so the biological
      attribute of modified chitosan must be evaluated. In this study, the
      biocompatibility of chitosan modified by several methods was carefully evaluated
      at the cellular and protein levels using different physical and biological
      methods. The results provide a theoretical basis for screening biomaterials. We
      studied the properties of five kinds of materials made by blending chitosan with
      different types of polyethylene glycol (PEG). The properties included physical
      and chemical properties, such as mechanical strength, static contact angle,
      spectroscopy, thermodynamic attributes and so on. The mechanical properties were
      slightly improved with the proper amount of PEG, but the improvement was not
      obvious and was destroyed by the wrong proportion of PEG. Cultures of the cells
      and amounts and structures of the adsorbed proteins on different materials showed
      that the PEG effectively improved the biocompatibility of the materials. The PEG
      enhanced the protein adsorption, cell adhesion, growth and proliferation, but the
      effects were impaired by excessive PEG. The experiments also demonstrated that
      the optimum PEG concentration helped to maintain the natural structure of the
      protein adsorbed on the materials and that maintaining the natural structure
      benefited cell growth. Analysis of the results based on the intramolecular and
      intermolecular interaction forces leads to a basic theory for the modification of
      biomaterials.

PMID- 12059014
TI  - In vitro and in vivo degradation studies for development of a biodegradable patch
      based on poly(3-hydroxybutyrate).
AB  - For the development of a resorbable gastrointestinal patch, the in vitro
      degradation of solution-cast films of poly(3-hydroxybutyrate) (PHB),
      modifications of PHB expected to influence its degradation time, as well a poly(L
      lactide) (PLLA) was examined. The molecular weight of pure PHB decreased by one
      half after 1 year in buffer solution (pH 7.4, 37 degrees C). Acceleration in
      molecular weight decrease was observed by blending with atactic PHB, whereas no
      influence was found with low-molecular weight PHB. Leaching of a water-soluble
      additive led to a slight acceleration of PHB degradability. In contrast, a
      deceleration in degradation rate was observed with the addition of a hydrophobic
      plasticizer. In vitro tests indicated an accelerating effect of pancreatin on PHB
      degradation, whereas PLLA degradation remained essentially uninfluenced. In
      comparison to simple hydrolysis, the degradation rate of PHB was accelerated
      about threefold. From the in vitro results, a PHB/atactic PHB blend was selected
      for repair of a bowel defect in Wistar rats. A patch film was fabricated by a
      dipping/leaching method. Twenty-six weeks post-implantation, material remnants
      were found in only one of four animals. The bowel defects were closed in all
      cases. It could be assessed that the patch material resists the intestinal
      secretions for a sufficiently long time but that it finally degrades completely.

PMID- 12059016
TI  - Finite element analysis of a glass fibre reinforced composite endodontic post.
AB  - In this work the mechanical response to external applied loads of a new glass
      fibre reinforced endodontic post is simulated by finite element (FE) analysis of
      a bidimensional model. The new post has a cylindrical shape with a smooth conical
      end in order to adequately fit the root cavity, and to avoid edges that could act
      as undesired stress concentrators. Mechanical data obtained by three-point
      bending tests on some prototypes fabricated in the laboratory are presented and
      used in the FE model. Under various loading conditions, the resulting stress
      component fields are hence compared with those obtained in the case of two
      commercial endodontic posts (i.e. a cast metal post and a carbon fibre post) and
      with the response of a natural tooth. The gold cast post-and-core produces the
      greatest stress concentration at the post-dentin interface. On the other hand,
      fibre-reinforced composite posts do present quite high stresses in the cervical
      region due to their flexibility and also to the presence of a less stiff core
      material. The glass fibre composite shows the lowest peak stresses inside the
      root because its stiffness is much similar to dentin. Except for the force
      concentration at the cervical margin, the glass fibre composite post induces a
      stress field quite similar to that of the natural tooth.

PMID- 12059015
TI  - Chemically modified polysulfone hollow fibers with vinylpyrrolidone having
      improved blood compatibility.
AB  - Hydrophilic polysulfone membranes (PVP-PSf) were prepared from polysulfone
      membranes covalently conjugated with polyvinylpyrrolidone (PVP) on the surface.
      The immobilized amount of vinylpyrrolidone on PVP-PSf membranes was controlled by
      the amount of vinylpyrrolidone monomer in the reaction solution and the reaction
      time. The PVP-PSf membranes were found to be the most hydrophilic membranes among
      the polysulfone and surface-modified polysulfone membranes prepared in this
      study. This is explained by the long hydrophilic side chain of
      polyvinylpyrrolidone on the PVP-PSf membranes which contributes to the
      hydrophilic wiper on the hydrophobic PSf membranes. It was found that PVP-PSf
      membranes gave lower protein adsorption from a plasma solution than polysulfone
      and other surface-modified membranes (p < 0.01). This is attributed to the
      hydrophilic surface of the PVP-PSf membranes, because the hydrophilic surface is
      known to reduce the protein adsorption on the membranes. The PVP-PSf membranes
      showed a much suppressed number of adhering platelets on the surface than
      polysulfone and other surface-modified membranes (p < 0.01). It is suggested that
      the hydrophilic surface of the PVP-PSf membranes without ionic groups causes the
      suppression of platelet adhesion on the PVP-PSf membranes and that the long
      hydrophilic side chain of polyvinylpyrrolidone on PVP-PSf membranes contributes
      to the hydrophilic and hemocompatible wipers on the surface of the hydrophobic
      PSf membranes.

PMID- 12059017
TI  - Controlled release of NFkappaB decoy oligonucleotides from biodegradable polymer
      microparticles.
AB  - The objective of this study was to evaluate a poly(DL-lactic-co-glycolic
      acid)/poly(ethylene glycol) (PLGA/PEG) delivery system for nuclear factor-kappa B
      (NFkappaB) decoy phosphorothioated oligonucleotides (ODNs). PLGA/PEG
      microparticles loaded with ODNs were fabricated with entrapment efficiencies up
      to 70%. The effects of PEG contents (0, 5, and l0 wt%), ODN loading densities
      (0.4, 4, and 40 microg/mg), and pH of the incubation medium (pH 5, 7.4. and 10)
      on ODN release kinetics from the PLGA/PEG microparticles were investigated in
      vitro for up to 28 days. The release profiles in pH 7.4 phosphate buffered saline
      (PBS) were characterized by an initial burst during the first 2 days, a linear
      release phase until day 18, and a final release phase for the rest of the period.
      Up to 85% of the ODNs were released after 28 days in pH 7.4 PBS regardless of the
      ODN loading density and PEG content. Higher ODN loading densities resulted in
      lower entrapment efficiencies and greater initial burst effects. The bulk
      degradation of PLGA was not significantly affected by the PEG content and ODN
      loading density, but significantly accelerated at acidic buffer pH. Under acidic
      and basic conditions, the aggregation of microparticles resulted in significantly
      lower cumulative mass of released ODNs than that released at neutral pH. The
      effects of pH were reduced by the incorporation of PEG into PLGA microparticles.
      Since the PLGA degradation products are acidic, PLGA/PEG microparticles might
      provide a better ODN delivery vehicle than PLGA microparticles. These results
      suggest that PLGA/PEG microparticles are useful as delivery vehicles for
      controlled release of ODNs and merit further investigation in cell culture and
      animal models of glioblastoma.

PMID- 12059018
TI  - Tissue responses to nacreous implants in rat femur: an in situ hybridization and
      histochemical study.
AB  - The interface of bone and aragonite nacre (Margaritifera, fresh water pearl
      mussel) was studied by in situ hybridization and a tartrate-resistant acid
      phosphatase (TRAP) histochemical assay. Columnar implants were inserted into rat
      femora for 4, 7, 14, 28 and 56 days. In medullary region, a burst of transient
      bone formation was observed, which propagated from the periphery towards the
      nacre implant. A fused interface of bone and nacre was observed at 14 days.
      Later, the new medullary bone was resorbed and bone marrow was re-established
      while a thin layer of bone tissue remained covering the implant surface.
      Expressions of collagen alpha1(I), osteocalcin, osteopontin mRNAs and TRAP in the
      surrounding tissue were monitored. Correlated with the histology events, a strong
      transient induction of collagen alpha1(I) and osteocalcin mRNAs as well as TRAP
      expression, exhibiting a peak signal intensity on day 7 and subsequent down
      regulation after day 14 was observed. Osteopontin mRNA, in contrast, was
      expressed continuously. The degrading nacre surface appeared in direct contact
      with macrophages and multinucleated giant cells at both days 14 and 28. These
      cells expressed osteopontin mRNA intensively and some TRAP enzyme activity
      occasionally.

PMID- 12059019
TI  - In situ crosslinking of a biomimetic peptide-PEG hydrogel via thermally triggered
      activation of factor XIII.
AB  - There is a medical need for robust, biocompatible hydrogels that can be rapidly
      crosslinked in situ through the use of gentle and non-toxic triggers, which could
      be used as a surgical adhesive, a bone-inductive material, or for drug and gene
      delivery. The complete gelation system described here includes calcium-loaded
      liposomes, hrFactor XIII. thrombin, and an enzymatic substrate based on a four
      armed PEG in which each arm terminates with a 20mer peptide sequence derived from
      the gamma-chain of fibrin. Controlled release of calcium ions for efficient
      hrFXIII activation was accomplished by thermal triggering of a tailored liposome
      phase transition at 37 degrees C, which allowed the entire gelation system to be
      stored in aqueous solution at room temperature without premature gelation. When
      the system temperature was raised to 37 degrees C (body temperature), the
      released calcium activates the hrFactor XIII, and gelation was observed to occur
      within 9 min. Rheological studies performed to quantitatively determine the
      storage modulus (G') of the gel during oscillatory shear show that it behaves as
      a robust, elastic solid. Scanning electron microscopy studies revealed the
      hydrogel to have a very dense morphology overall, however spherical voids are
      observed in regions where calcium-loaded liposomes were entrapped during
      gelation.

PMID- 12059020
TI  - Osteogenic response of hydroxyapatite cement implanted into the femur of rats
      with experimentally induced osteoporosis.
AB  - Hydroxyapatite (HAP) cement was implanted in the femur of rats with
      experimentally induced osteoporosis, and the osteogenic response was studied
      histomorphologically. Osteoporosis was induced with ovariectomy with either a
      normal diet or a low-calcium diet. The rats fed a low-calcium diet after
      ovariectomy showed a decrease in both cumulative photodensity and the cortical
      thickness index. There was significant bone conduction in the femur of these
      rats, but the development of new bone was late, and the affinity index was small.
      The change in the affinity index with time was similar between the ovariectomy
      group and the ovariectomy/low calcium-group, suggesting the possibility that
      estrogen plays a major role in bone conduction.

PMID- 12059021
TI  - Biocompatibility of thermosensitive chitosan-based hydrogels: an in vivo
      experimental approach to injectable biomaterials.
AB  - Chitosan, an amino-polysaccharide obtained from the alkaline deacetylation of
      chitin, presents an interest as a drug vehicle. Indeed, chitosan solutions
      containing glycerol-2-phosphate (beta-GP) undergo sol-gel transition at a
      temperature close to 37 degrees C, which make them suitable for the parenteral
      administration of drugs. However, before using these chitosan derivatives for
      biomedical applications, it is important to evaluate their biocompatibility, and
      particularly to test their inflammatory effects. When injected in the hindpaw of
      the rat, we have shown that: (i) four chitosan/beta-GP solutions tested triggered
      a non-specific response, with solutions prepared with chitosans of higher
      deacetylation degrees yielding a lesser inflammatory reaction and (ii) systemic
      pretreatment of animals with icatibant, apafant and diphenhydramine did not
      significantly diminish this response; dexamethasone practically abolished it for
      all solutions and ketanserine only slightly decreased it in one preparation at
      two different times. In conclusion, it appears that a higher degree of
      deacetylation of the chitin chain is desirable for superior biocompatibility.

PMID- 12059022
TI  - Localized delivery of paclitaxel in solid tumors from biodegradable chitin
      microparticle formulations.
AB  - Paclitaxel (Taxol)-containing chitin and chitin-Pluronic F-108 microparticles
      were formulated as biodegradable systems for localized administration in solid
      tumors. The microparticles were characterized by Fourier transform infrared (FT
      IR) spectroscopy, scanning electron microscopy (SEM), and swelling studies in
      phosphate-buffered saline (PBS, pH 7.4). Lysozyme-induced degradation and in
      vitro release of paclitaxel was examined in PBS at 37 degrees C. The percent
      change in tumor volume was used to assess efficacy of the Formulations after
      local administration in murine Lewis lung carcinoma model. FT-IR confirmed higher
      degree of acetylation in chitin microparticles from the starting chitosan sample
      and the SEM showed that the chitin-Pluronic F-108 microparticles were
      significantly more porous than chitin microparticles. Due to higher porosity,
      chitin-Pluronic microparticles were able to imbibe higher swelling medium and
      degraded much faster in the presence of lysozyme than chitin microparticles.
      After 48 h. 51% of incorporated paclitaxel was released from chitin-Pluronic
      microparticles as compared to 28% from chitin microparticles. In vivo studies in
      Lewis lung carcinoma-bearing mice showed that the tumor volumes after 6 days
      using paclitaxel-loaded chitin and chitin-Pluronic F-108 microparticles was 458
      and 307 mm3, respectively. In contrast, the tumor volume was 997 mm3 for the
      untreated control. The results of this study show that chitin and chitin-Pluronic
      F-108 microparticles are biodegradable drug delivery systems that can be useful
      for localized delivery of paclitaxel in solid tumors.

PMID- 12059023
TI  - The effects of low-intensity pulsed ultrasound on bioabsorbable self-reinforced
      poly L-lactide screws.
AB  - The effects of low-intensity pulsed ultrasound on the mechanical and molecular
      properties of self-reinforced poly L-lactide (SR-PLLA) screws were studied in
      vitro. SR-PLLA screws of 4.5 mm diameter were exposed on low-intensity ultrasound
      for 1, 3. 6, 9, and 12 weeks. After exposure, the bending strength, shear
      strength, and molecular weight were investigated. There were no differences in
      the investigated properties between the ultrasound exposure and control groups.
      We found no evidence that low-intensity ultrasound has any effect on the
      mechanical or molecular properties of SR-PLLA screws in vitro. The present
      results suggest that biodegradable SR-PLLA fixation devices are compatible with
      low-intensity ultrasound in vitro.

PMID- 12059024
TI  - Evaluation of MEMS materials of construction for implantable medical devices.
AB  - Medical devices based on microelectro-mechanical systems (MEMS) platforms are
      currently being proposed for a wide variety of implantable applications. However,
      biocompatibility data for typical MEMS materials of construction and processing,
      obtained from standard tests currently recognized by regulatory agencies, has not
      been published. Likewise, the effects of common sterilization techniques on MEMS
      material properties have not been reported. Medical device regulatory
      requirements dictate that materials that are biocompatibility tested be processed
      and sterilized in a manner equivalent to the final production device. Material,
      processing, and sterilization method can impact the final result. Six candidate
      materials for implantable MEMS devices, and one encapsulating material, were
      fabricated using typical MEMS processing techniques and sterilized. All seven
      materials were evaluated using a baseline battery of ISO 10993 physicochemical
      and biocompatibility tests. In addition, samples of these materials were
      evaluated using a scanning electron microscope (SEM) pre- and post-sterilization.
      While not addressing all facets of ISO 10993 testing, the biocompatibility and
      SEM data indicate few concerns about use of these materials in implant
      applications.

PMID- 12059025
TI  - Influence of apatite seeds on the synthesis of calcium phosphate cement.
AB  - This preliminary study explores the seeding effect (using crystalline
      hydroxyapatite particles) on the setting time, compressive strength, phase
      evolution, and microstructure of calcium phosphate cements (CPC) based on
      monocalcium phosphate monohydrate and calcium hydroxide. Experimental results
      showed that the setting time varies from 5 to about 30 min, as the seed
      concentration increased from 0 to 20 wt%. The compressive strength of CPC
      increased from 4 to 17 MPa, followed by decrease to 12 MPa, for the same range of
      seeds content. The CPC transformed to predominantly apatitic structure within 24
      h for all the samples, with or without the seeds. However, increase of the seed
      concentration improved the final crystallinity of the apatite phase, suggesting
      nucleation and growth effects during precipitation of CPC from the precursor
      solution. The microstructure of the resulting apatitic cement showed a change
      from essentially featureless (or glass-like) to thin, elongated plate-like
      morphology, as seeds concentration increased. Correlation between microstructural
      evolution and corresponding compressive strength of seeded CPC is investigated.

PMID- 12059026
TI  - In vitro degradation of chitosan by bacterial enzymes from rat cecal and colonic
      contents.
AB  - The degradative activities of extracellular and cell-associated portions of rat
      cecal and colonic enzymes, whose activities are comparable to that in the human
      colon, against five chitosan samples were characterized. The effects of the
      molecular weight (MW) and degree of deacetylation (DD) of chitosan on its
      susceptibility to degradation were investigated. In addition, the degradation
      function of rat bacterial enzymes was compared to that of a commercially
      available almond emulsin beta-glucosidase that contains a chitinase. The results
      show that rat bacterial enzymes had the ability to degrade chitosan with
      extracellular enzymes exhibiting a more profound effect than did cell-associated
      enzymes. The reaction to bacterial enzymes degradation was dependent on both the
      MW and DD of the chitosan sample. Those samples with a lower MW and lower DD were
      more susceptible substrates. A similar degradation function of rat bacterial
      enzymes and of almond emulsin beta-glucosidase on chitosan was revealed, which
      indicates that almond emulsin beta-glucosidase might be able to be used as an in
      vitro enzyme system to predict the large intestinal degradation of chitosan.

PMID- 12059027
TI  - Oxygen permeability of hydrogel contact lenses with organosilicon moieties.
AB  - Oxygen transport through two extended wear (day and night) hydrogel contact
      lenses that contain organosilicon moieties (balafilcon A and lotrafilcon A) was
      studied in the hydrate (hydrogel) and dry (xerogel) states. The water uptake
      increased the oxygen permeability [(Dk)app] and transmissibility [Dk/L(av)]
      coefficients of the dry materials by about 70%. The (Dk)app for the hydrated
      lenses was determined following the so-called stack procedure. The values
      obtained were 107 +/- 4 barrer for balafilcon A and 141 +/- 5 barrer for
      lotrafilcon A, about 5-10 times larger than those previously reported for
      conventional (without organosilicon moieties) extended wear hydrogels contact
      lenses. The Dk/L(av) for -3.00 diopter lenses (harmonic average thickness, L(av)
      = 75 +/- 2 microm for lotrafilcon, and 85 +/- 2 microm for balafilcon) was 123 +/
      6 barrer/cm for balafilcon A and 183 +/- 8 barrer/cm for lotralicon A. The
      minimum oxygen transmissibility 87 barrer/cm stipulated by Holden and Mertz to
      avoid corneal edema with extended wear contact can be easily achieved with
      lotrafilcon and balafilcon lenses of diverse dioptric powers if the central and
      peripheral thickness of the lenses are kept below the critical level of oxygen
      transmissibility.

PMID- 12059029
TI  - Buffering and ion-release by a glass-ionomer cement under near-neutral and acidic
      conditions.
AB  - Specimens of an experimental glass-ionomer cement were stored in water (initial
      pH 5.9) and aqueous lactic acid (initial pH 2.7) for storage periods of 1 week up
      to 6 weeks. Change in mass, solution pH and fluoride release were measured at
      weekly intervals, and other ions were determined at weeks 1, 2, 4 and 6. In
      water, cements raised the pH consistently to 6.7-6.9 from weeks 2 to 6, but this
      did not correspond to uniform amounts of ions released, nor even to consistent
      mole ratios of ions in solution. Similarly, in lactic acid, pH was raised to
      between 3.6 and 4.5, but without a consistent concentration of ions in solution.
      In near neutral conditions, calcium was found to be virtually insoluble and
      remained within the cement, whereas reasonable amounts of sodium, aluminium,
      phosphorus, silicon and fluoride were released at all time intervals, with
      downward trends over time. In acidic conditions, considerable amounts of calcium
      were released over time, and amounts of calcium, aluminium, phosphorus and
      silicon increased with time, reaching a maximum in week 4. This suggests that as
      maturation proceeds, there is an increase in the acid-soluble fraction of the
      cement containing these elements. Fluoride release was found to be as previously
      reported, i.e. greater amounts in the early stages of the experiment, and with a
      gradual decline, and with greater amounts in acid than in water. Determination of
      fluoride with and without the decomplexing reagent TISAB showed that 70-75% of
      the total fluoride was released in "free" form in water for most weeks, whereas
      in acid, it declined sharply and by week 6, an estimated total of 96% of the
      fluoride released was complexed.

PMID- 12059028
TI  - Effects of NFkappaB decoy oligonucleotides released from biodegradable polymer
      microparticles on a glioblastoma cell line.
AB  - The objectives of this study were to investigate a nuclear factor-kappa B
      (NFkappaB) decoy oligonucleotide (ODN) strategy on the inhibition of glioblastoma
      (GBM) cell line growth and to evaluate a poly(DL-lactic-co-glycolic acid) (PLGA)
      microparticle delivery system for the NFKB decoy ODNs in vitro. We have
      demonstrated that NFkappaB activation is important in regulating GBM cell line
      growth. Aberrant nuclear expression of NFkappaB was found in a panel of GBM cell
      lines, while untransformed glial cells did not display NFkappaB activity. Nuclear
      translocation of NFkappaB was inhibited by using a 'decoy" ODN strategy. NFkappaB
      decoy ODNs designed to inhibit NFkappaB resulted in a significant reduction in
      cell number (up to 45%) compared to control cultures after 2 days. The reduction
      in cell number correlated with a decrease in cyclin D1 protein expression and a
      commensurate decrease in Cdk-4 activity. These results provide evidence
      suggesting that NFkappaB mediates cell cycle progression and demonstrates a
      mechanism linking increased NFkappaB activity with GBM cell growth and cell cycle
      disregulation. Decoy ODNs were encapsulated at a yield of 66% in PLGA
      microparticles and released in a controlled manner in phosphate buffered saline
      for up to 28 days. Approximately 83% of entrapped ODNs were released by day 28.
      During 3 days of GBM cell line culture, the released decoy ODNs retained their
      biologic activity and led to significantly reduced cell number as compared to
      control cultures. These findings offer a potential therapeutic strategy in the
      control of human GBM cell line growth in vitro and suggest that PLGA
      microparticles may be appropriate as delivery vehicles for the "decoy" ODN
      strategy.

PMID- 12059030
TI  - Crystallization at the polymer/calcium-phosphate interface in a sterilized
      injectable bone substitute IBS.
AB  - Calcium phosphate (CaP) ceramics are the main raw materials used to elaborate
      blocks or granules for bone substitutes. In this study, injectable bone
      substitutes (IBS) were developed for applications in orthopedic or dental
      surgery. Sterile, ready-to-use composite containing CaP granules (biphasic
      calcium phosphate, BCP) and polymer (hydroxypropylmethylcellulose, HPMC) was
      prepared. Steam sterilization produced new phenomena at the CaP/polymer
      interface, resulting in crystal growth. These phenomena may constitute a model
      for the biomineralization study. Scanning electron microscopy showed that the
      formed crystallites organize themselves into a three-dimensional structure.
      Currently, the mechanisms of crystal growth are unknown and have been observed
      with only one combination of polymer/BCP ceramics after steam sterilization.

PMID- 12059031
TI  - Effect of synthesis parameters of the sol-gel-processed spray-dried silica gel
      microparticles on the release rate of dexmedetomidine.
AB  - The objective of this study was to evaluate the possibilities to control the
      release rate of dexmedetomidine (DMED) from different spray-dried silica gel
      microparticle formulations. Microparticles were prepared by spray drying a silica
      sol polymer solution containing the drug. Drug release was investigated both in
      vitro and in vivo. The influence of sol-gel synthesis parameters, like pH and the
      water/alkoxide ratio (r) of the sol, on the release behaviour of the drug was
      studied. Silica gel microparticles had a smooth surface. Microparticles prepared
      from diluted sol, however, were more aggregated and clustered. The drug release
      conformed to zero order release from microparticles prepared near the isoelectric
      point of silica (pH 2.3 and pH 3) and to the square root of time kinetics from
      microparticles prepared at pH 1 and pH 5. The release also showed a dual-phasic
      profile with an initial burst and after that a slower release period. The
      dexmedetomidine release conformed to zero order kinetics from microparticles
      prepared at water/ alkoxide ratios between r = 6 and r = 35 (at pH 2.3). The
      release rate was the slowest from microparticles prepared with water/ alkoxide
      ratio 35. The bioavailability of dexmedetomidine in dogs showed that the release
      was sustained from silica gel microparticles as compared with a subcutaneously
      administered reference dose of 0.1 mg.

PMID- 12059032
TI  - Ex vivo PMA-induced respiratory burst and TNF-alpha secretion elicited from
      inflammatory cells on machined and porous blood plasma clot-coated titanium.
AB  - The release of inflammatory mediators around implants and normal wounds may
      differ due to the presence of the solid surface. In this study, machined and sub
      micron porous titanium implants with and without a 100 nm thick blood plasma clot
      were inserted subcutaneously in rat for 3 or 24 h. The cell recruitment to the
      interfaces, in vivo secretion of TNF-alpha and the ex vivo PMA-induced production
      of reactive oxygen species were subsequently investigated. The thin plasma clot
      coating gave rise to an increased ex vivo PMA-stimulated oxygen radical
      production by implant-associated cells at both implantation times, and an
      increased cell recruitment at 24 h. The total TNF-alpha secretion was highest at
      sham sites and plasma clot-coated porous titanium at 24 h. After 24 h, the cell
      type pattern in the exudate around the porous plasma-coated implant was more
      similar to that found at sham sites than that adjacent to the non-coated
      implants. No differences were observed between the machined Ti and the machined
      sub-micron porous Ti.

PMID- 12059033
TI  - Adsorption of proteins and calcium phosphate materials bioactivity.
AB  - The behaviour of calcium phosphate (CaP) based biomaterials in biological
      environments determines how they can be used in vivo. The prime requirement for
      CaP materials to be bioactive and bond to living bone is the formation of a bone
      like apatite layer on their surface. This phenomenon can be reproduced in vitro
      using simulated body fluid (SBF): a protein-free solution with ion concentrations
      similar to those of human blood plasma. Although proteins are unanimously
      considered as important actors in CaP material bioactivity and biomineralization
      processes, a certain confusion exists about their role as promotors or inhibitors
      of mineral crystal formation or both. The adsorption of proteins on the mineral
      surface can alter the nucleation rate and lead to antagonistic effects depending
      on the concentration of the adsorbed proteins. The ambiguity of this general
      effect is illustrated by the action of albumin on calcium phosphate
      crystallization on type I collagen and several other examples found in the
      literature.

PMID- 12059034
TI  - Protein synthesis in nuclei: when did the story start?

PMID- 12059035
TI  - Immunological characterization of 5-HT3 receptor transmembrane topology.
AB  - The 5-hydroxytryptamine3 (5-HT3) receptor is a member of the Cys-loop family of
      ligand-gated ion channels. These receptors are pentamers with the greatest
      homology to nicotinic acetylcholine (nACh) receptors. The proposed topological
      organization of a 5-HT3 receptor subunit is based largely on hydropathy profiles
      and by homology to nACh receptors, and indicates a large N-terminal extracellular
      domain and four transmembrane regions. There is, however, little direct evidence
      for this model. We therefore investigated the topology of the 5-HT3A receptor
      subunit using a panel of 5-HT3 receptor-specific antisera that interact with
      defined regions of the receptor. An antiserum generated against a short peptide
      from the N-terminal domain of the 5-HT3A receptor subunit, pAb120, was shown to
      bind to 5-HT3 receptor-expressing cells with intact cell membranes, indicating
      that the N-terminal end of the subunit is extracellular. Two antisera generated
      against regions of the loop between predicted transmembrane regions three and
      four did not bind to cells with intact membranes. However on membrane
      permeabilization these antibodies both bound to the receptor in intracellular
      areas, thus indicating that the loop between transmembrane domains three and four
      is intracellular. These data therefore provide direct evidence for an
      extracellular N-terminal domain and an intracellular loop between the third and
      fourth transmembrane domains, thus supporting the conventional ligand-gated ion
      channel subunit topological model.

PMID- 12059036
TI  - Increase of acidic fibroblast growth factor in the brains of hamsters infected
      with either 263K or 139H strains of scrapie.
AB  - Scrapie is the archetypal unconventional slow infection disease. It has been
      shown that hamsters injected intracerebrally with scrapie strains 139H or 263K
      show extensive astrocytosis and that the induced reactive astrocytes produce a
      variety of factors that can affect brain function. Acidic fibroblast growth
      factor (aFGF) belongs to a family of growth factors that show a high affinity for
      heparin sulfate proteoglycans. In the current study, we have used
      immunohistochemistry to investigate the distribution of aFGF in scrapie-infected
      brain; we observed a low level of aFGF immunoreactivity (ir-aFGF) in ependymal
      cells and in a few neurons in the hypothalamus of control hamsters. In contrast,
      in scrapie-infected hamsters, there was an increase of ir-aFGF in a number of
      cell types, including neurons, pericytes, astrocytes, and ependymal cells. In
      139H-infected hamsters, ir-aFGF staining in astrocytes, neurons and neuropil
      areas of the cortex, hippocampus, thalamus, and hypothalamus was greater than the
      staining in control animals. For 263K animals, astrocytic ir-aFGF staining was
      significantly greater than in either control or 139H-infected hamsters in the
      following regions: cortex, putamen, corpus callosum, thalamus, hypothalamus,
      fimbria, hippocampus, subependymal areas, and amygdala. In addition, there was a
      significant increase in neuronal ir-aFGF in the CA1 hippocampal area and in the
      amygdala. Our results suggest that neurons and astrocytes can produce and/or
      absorb aFGF during scrapie infection. These findings indicate that aFGF might
      play an important role in neuronal protection and in astrocytosis in scrapie
      infected hamsters.

PMID- 12059037
TI  - Reduction of trophic support enhances apoptosis in PC12 cells expressing
      Alzheimer's APP mutation and sensitizes cells to staurosporine-induced cell
      death.
AB  - Mutations in the amyloid precursor protein (APP) gene are known as causative
      factors in the pathogenesis of early-onset familial Alzheimer's disease (FAD). In
      this study, the influence of the Swedish double-mutation form of APP (APPsw;
      KM670/671NL) on apoptosis regulation in PC12 cells was investigated. APPsw
      transfected PC12 cells were compared with wild-type APP (APPwt)-expressing and
      vector-transfected PC12 cells with regard to their susceptibility to cell death
      induced by the reduction of trophic support or by additional treatment with
      staurosporine. Expression of APPsw markedly enhanced the level of apoptotic PC12
      cells induced by serum reduction. A similar hypersensitivity of APPsw-expressing
      PC12 cells could be detected after differentiation with nerve growth factor under
      serum-reduced conditions. Likewise, the expression of APPsw rendered PC12 cells
      more vulnerable to staurosporine but only under serum-reduced conditions. This
      APPsw-effect disappeared in high serum-containing medium. Thus, expression of
      APPsw seems to enhance cellular sensitivity not in general but after the
      reduction of trophic factors probably by causing oxidative stress. This, in turn,
      may sensitize cells to secondary apoptotic stimuli. Moreover, the mutation
      specific increase in vulnerability to cell death was only seen at the stage of
      apoptotic nuclei, but not using methods measuring cell death by determining
      metabolic activity or membrane integrity. Therefore, the expression of APPsw
      seems to affect specifically apoptotic cell death rather than overall cell death
      in vitro. Our study further emphasizes the pathogenic role of mutant APP and may
      provide new insights in the mechanisms underlying the massive neurodegeneration
      in brain from patients bearing the APPsw mutation.

PMID- 12059038
TI  - LVV-hemorphin-4 modulates Ca2+/calmodulin-dependent pathways in the immune system
      by the same mechanism as in the brain.
AB  - The effect of synthetic LVV-hemorphin-4 (LVV-H4) on human blood and tonsils
      lymphocytes total phosphatase activity was studied by a spectrofluorimetric assay
      using 4-methylumbelliferyl phosphate (4-MUP) as a substrate. It has been
      established that LVV-H4 at concentrations of 10(-9) to 10(-7) M induces the
      inhibition of human blood (12-24%) and tonsils (42-45%) lymphocytes total
      phosphatase activity as 1 mM EGTA. The same peptide at concentrations of 10(-5)
      to 10(-4) M induces activation of human blood (48-57%) and tonsils (20-25%)
      lymphocytes total phosphatase activity. LVV-H4 is able to neutralize the
      inhibitory effect of calmodulin (CaM) antagonist and calcineurin inhibitor
      trifluoperazine (TFP) on human blood lymphocyte total phosphatase activity. It is
      suggested that a dose-dependent activation/inhibition of lymphocytes total
      phosphatase activity is due to activation/inhibition of lymphocyte calcineurin
      activity. Using enzyme-linked immunosorbentassay (ELISA) it was found that LVV-H4
      neutralized the inhibitory effect of cyclosporin A (CsA) and TFP on interleukin-2
      (IL-2) synthesis by activated blood lymphocytes. LVV-H4 also affects the
      lymphocytes proliferation, suppressed in pathophysiological condition, and
      restores their function by enhancement of DNA synthesis, as determined by
      measuring of [3H] thymidine incorporation into lymphocytes. It has been proposed
      that CaM is an essential component in starting up the molecular mechanism of
      hemorphins action and that calcineurin is a key enzyme underlying the molecular
      mechanism of hemorphins action on the brain and immune system.

PMID- 12059039
TI  - Upregulation of neuronal nicotinic receptor subunits alpha4, beta2, and alpha7 in
      transgenic mice overexpressing human acetylcholinesterase.
AB  - Neuronal nicotinic receptor binding sites as well as mRNA levels encoding for
      subunits alpha4, beta2, and alpha7 were analysed in 3-mo-old transgenic mice
      generated with a neuronal overexpression of human acetylcholinesterase and in age
      matched controls. The acetylcholinesterase transgenic mice display progressive
      cognitive impairment in spatial learning and memory. We here report a
      significantly increased [3H]epibatidine and [125I]alphabungarotoxin binding in
      the cortex and the caudate putamen of these mice. Quantitativein situ
      hybridization showed significant upregulation of mRNA corresponding to the
      nicotinic receptor subunits alpha4, beta2, and alpha7 in various brain regions in
      the transgenic mice compared to nontransgenic controls. Our results suggest that
      disruption of balanced cholinergic transmission by constitutive overexpression of
      acetylcholinesterase is accompanied by variable upregulation of several nicotinic
      receptor subtypes, in particular these associated with cholinergic terminals
      participating in compensatory response.

PMID- 12059040
TI  - Dynamic processing of neuropeptides: sequential conformation shaping of
      neurohypophysial preprohormones during intraneuronal secretory transport.
AB  - Neurohypophysial preprohormones are single polypeptide chains folded into 3/4
      domains, namely a signal prepeptide (18/20 residues), a hormone peptide (9
      residues), and a propeptide neurophysin-copeptin (93/134 residues). Neuro-hormone
      and neurophysin contain 1 and 7 disulfide bridges, respectively, whose pairing
      depends on correct primordial folding within the endoplasmic reticulum (ER)
      compartment (pH 7.0) of hypothalamic magnocellular neurons. During intracellular
      travel in the secretory pathway from ER to secretory granules (SC), the precursor
      is submitted to successive processings (glycosylation, proteolysis, amidation) in
      distinct compartments, leading to domain separation and reshaping. In particular
      the hormone domain is subjected, in the SG, pH 5.5, to a 4-enzyme cascade in
      order to reach the bioactive conformation. We have purified SG from rat and ox
      neurohypophyses and characterized: 1) the processed domains (neurohormone,
      neurophysin, copeptin); 2) the four processing enzymes acting successively at the
      level of the processing sequence, namely a Lys-Arg calcium-dependent
      endopeptidase, a carboxypeptidase B-like enzyme, a peptidyl-glycine monooxygenase
      and a peptidyl-hydroxyglycine lyase (amidating enzyme). A reconstitution of the
      processing has been carried out in vitro using purified granular enzymes and
      synthetic nonactive prohormone peptides, vasopressinyl-Gly-Lys-Arg, vasotocinyl
      Gly, and oxytocinyl-Gly. Vasopressin (yield 17% at pH 6.0, 30% at pH 8.0) has
      been identified by both coelution in high-performance liquid chromotography
      (HPLC) and bioactivity. In the homozygote mutant Brattleboro rats, a single
      nucleotide deletion in the gene entails a complete change in aminoacid sequence
      of neurophysin from residue 64 onwards. A misrouting in the ER or a misprocessing
      in the SG could occur so that neither vasopressin nor associated-neurophysin are
      found in the neurohypophysis, this lack determining diabetes insipidus. In
      addition there is a 50% decrease of the Lys-Arg-endoendopeptidase activity in the
      SG of the homozygote Brattleboro.

PMID- 12059041
TI  - Mutant and wild-type alpha-synuclein interact with mitochondrial cytochrome C
      oxidase.
AB  - Alpha-synuclein, a presynaptic protein, was found to be the major component in
      the Lewy bodies (LB) in both inherited and sporadic Parkinson's disease (PD).
      Furthermore, rare mutations of alpha-synuclein cause autosomal-dominant PD.
      However, it is unknown how alpha-synuclein is involved in the pathogenesis of
      nigral degeneration in PD. In this study, we examine the protein-protein
      interactions of wild-type and mutant (A53T) a-synuclein with adult human brain
      cDNA expression library using the yeast two-hybrid technique. We found that both
      normal and mutant alpha-synuclein specifically interact with the mitochondrial
      complex IV enzyme, cytochrome C oxidase (COX). Wild-type and mutant alpha
      synuclein genes were further fused with c-Myc tag and translated in rabbit
      reticulocyte lysate. Using anti-c-Myc antibody, we demonstrated that both wild
      type and mutant alpha-synuclein, coimmunoprecipitated with COX. We also showed
      that potassium cyanide, a selective COX inhibitor, synergistically enhanced the
      sensitivity of SH-SY5Y neuroblastoma cells to dopamine-induced cell death. In
      conclusion, we found specific protein-protein interactions of alpha-synuclein, a
      major LB protein, to COX, a key enzyme of the mithochondrial respiratory system.
      This interaction suggests that alpha-synuclein aggregation may contribute to
      enhance the mitochondrial dysfunction, which might be a key factor in the
      pathogenesis of PD.

PMID- 12059042
TI  - Neuroendocrine modulation of olfactory sensory neuron signal reception via axo
      dendritic synapses in the antennae of the mosquito, Aedes aegypti.
AB  - An ultrastructural study of the antennae of the yellow fever mosquito, Aedes
      aegypti, revealed that as in the salt marsh mosquito, Culex salinarius, the first
      flagellar segment of both sexes of A. aegypti contain neuroendocrine cells. These
      cells not only extend an axon via the antennal nerve to the antennal lobe of the
      deutocerebrum, but project collaterals to the periphery of the antennae, where
      they modulate the antennal sensory neurons by forming synapses with the dendrites
      of these afferent neurons. To our knowledge, this is the first report in any
      animal of neurites of neuroendocrine cells forming axo-dendritic synapses with
      sensory neurons.

PMID- 12059043
TI  - Changes in regional energy metabolism after cortical cold lesion in the rat
      brain.
AB  - In the present investigation, regional ATP, glucose, and lactate contents were
      examined in the cortical and subcortical structures after cold lesion in rats.
      Bioluminescence imaging of ATP, glucose, and lactate was performed in serial
      tissue sections at 4 h (n = 4), 12 h (n = 4) and 24 h (n = 4) after cold injury
      or sham surgery. Bioluminescence images were analyzed by computer-assisted
      densitometry, at the lesion site, in cortical areas, in the hippocampus, and in
      the thalamus. ATP and glucose content were significantly decreased at the lesion
      site as well as on the contralateral side after 4, 12, and 24 h postinjury
      Lactate content increased significantly in the hippocampal area on the
      ipsilateral side at 12 h. Cortical lactate was bilaterally unchanged. The cold
      lesion injury led to a characteristic ischemic profile in the hippocampus
      signaled by low ATP and glucose content paralleled by high lactate levels. The
      otherwise global depletion of glucose and ATP suggests that other factors besides
      cerebral blood flow may contribute to the impairment of energy metabolism.

PMID- 12059044
TI  - A quantitative bioassay for nerve growth factor, using PC12 clones expressing
      different levels of trkA receptors.
AB  - Nerve growth factor (NGF) is a neurotrophin required for differentiation,
      development, and survival of the sympathetic nervous system, with many of its
      biological effects being mediated via trkA receptors. There is a need for a
      standard quantitative bioassay for NGF, to be used in basic research and in
      pharmaceutical studies. The objective of the present research was to develop a
      selective, quantitative, and reliable bioassay for NGF, using a morphological
      criterion: neurite cell outgrowth. In addition, we aimed to apply the
      aforementioned bioassay to measure NGF administered to mice. Pheochromocytoma
      PC12 cell variants including wild-type cultures, and a trkA-overexpressing stable
      transfectant PC12-6.24-I, PC12nnr5, and PC12EN lacking trkA receptors, were used.
      Dose-response curves were generated with NGF beta-subunit (2.5S) purified from
      mouse submaxillary glands. Our results demonstrated that the bioassay was
      sensitive to 0.3-20 ng/mL, and selective, as neurite outgrowth was not seen by
      any other growth factor other than NGF. In addition, variant clones PC12nnr5 and
      PC12EN, lacking trkA receptors, did not respond to NGF. The bioassay detected NGF
      in serum of mice injected with NGF. This novel developed bioassay can serve as a
      model system for various neuroscience purposes.

PMID- 12059045
TI  - Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on
      neurons in culture.
AB  - Herbal products are being increasingly used as dietary supplements and
      therapeutic agents. However, much more research must be performed in order to
      determine the biological basis for their putative clinical effects. We tested the
      effects of milk thistle (Silybum marianum) extract on the differentiation and
      survival of cultured neural cells. Milk thistle enhanced nerve growth factor
      (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their
      survival in culture. Milk thistle extract also protected cultured rat hippocampal
      neurons against oxidative stress-induced cell death. Our data demonstrate that
      milk thistle extract can promote neuronal differentiation and survival,
      suggesting potential benefits of chemicals in this plant on the nervous system.

PMID- 12059046
TI  - Effects of the polyene antibiotic derivative MS-8209 on the astrocyte lysosomal
      system of scrapie-infected hamsters.
AB  - Amphotericine B (AmB), a macrolide polyene antibiotic, is one of a few drugs that
      has shown therapeutic properties in scrapie-infected hamster. Its beneficial
      effect on survival time is mostly marked when animals are treated with its
      derivative MS-8209. To explore the MS-8209 effect at the cellular level, we
      investigated at the light and electron microscopy levels, the sequential
      appearance and distribution of PrP concurrently with histopathological changes in
      hamsters that were infected intracerebrally with the 263 K scrapie strain and
      treated or not with the drug. The first histopathological modifications and PrP
      immunostaining were observed in the thalamus and at the inoculation site where
      the drug caused a delay in the appearance of lesions and PrP accumulation. Using
      immunoelectron microscopy, at 70 d postinfection, the inoculation site of
      untreated animals showed an accumulation of PrP in plaque areas constitued by
      filaments mixed with alterated membrane structures and in developed lysosomal
      system of reactive astrocytes. Most of the numerous lysosomes containing PrP
      showed intra-organelle filaments. In contrast, in MS-8209 treated animals, the
      number of lysosomes was significantly lower (p < 0.0038), with very few
      organelles harboring PrP. Our results suggest that in this scrapie model, MS-8209
      treatment delays the disease by preventing the replication of the scrapie agent
      at the inoculation site where the astrocytes appear to be the first cells
      producing abnormal PrP. The lysosomal system of these astrocytes could constitute
      a privileged target for MS-8209.

PMID- 12059048
TI  - Gastric acidity protects mice against prion infection?
AB  - BACKGROUND: The transmissible degenerative encephalopathies (TDEs) constitute a
      distinct group of diseases (scrapie in sheep, bovine spongiform encephalopathy
      (BSE) and Creutzfeldt-Jakob disease (CJD) in humans). The causal agents are not
      fully characterized, but are known to be resistant to most inactivation
      procedures. Ruminants appear to be particularly susceptible to TDEs. The
      concentrations of hydrochloric acid in their digestive tracts are significantly
      lower than in monogastric species. METHODS: The aim of the study was to examine
      the role of gastric acidity in the protection of mice against infection after
      intragastric administration of different doses of a scrapie agent. Gastric
      acidity levels in mice were reduced by adding ranitidine to the drinking water
      and the animals were observed for neurological symptoms and at sacrifice examined
      microscopically for spongiform lesions in the brain. RESULTS: The lower doses of
      infectious material induced disease significantly more often in mice given
      ranitidine compared with the controls. CONCLUSION: These data indicate that the
      normal levels of gastric acidity in mice protect them to some extent from
      infection with low doses of scrapie agent. This finding is potentially relevant
      to the pathogenesis of the variant form of CJD, which appears to be associated
      with the consumption of BSE-infected food products.

PMID- 12059047
TI  - A phase I study of AIT-082 in healthy elderly volunteers.
AB  - A Phase I, double-blind, placebo-controlled, single-dose, escalation study of the
      purine derivative, AIT-082 (Neotrofin, NeoTherapeutics, Inc.) was conducted in
      healthy elderly volunteers. This trial was designed to evaluate single-dose
      safety, tolerability, and pharmacokinetics. Potential cognitive domains that
      might benefit from AIT-082 were preliminarily investigated. AIT-082 is currently
      being developed as a potential treatment for Alzheimer's disease (AD).
      Preclinical studies indicate that AIT-082 has memory-enhancing properties,
      stimulates neuritogenesis, and upregulates neurotrophic factors. Subjects
      received a single oral dose of AIT-082 or placebo on a weekly basis for 5 wk. All
      patients received a placebo dose at baseline. Six subjects received increasing
      doses of AIT-082 over the next 4 wk at doses of 0.6, 2.0, 6.0, and 20.0 mg of AIT
      082 per kilogram of body weight. Two subjects received placebo throughout the
      trial. Nine subjects were recruited. One subject was withdrawn after the third
      treatment visit owing to poor venous access. There were no serious adverse
      events. The drug was well-tolerated. The time to peak drug concentration was
      approx 85 min with an elimination half-life of approx 17.6 h. Performance on the
      Number Comparison, Symbol Digit, and Trails A tests improved with AIT-082 dosing
      compared to baseline (placebo). In conclusion, AIT-082 was rapidly absorbed by
      the oral route with a half-life suitable for once daily dosing. No problems with
      tolerability or safety were demonstrated.

PMID- 12059049
TI  - Upregulation of mucosal soluble fas ligand and interferon-gamma may be involved
      in ulcerogenesis in patients with Helicobacter pylori-positive gastric ulcer.
AB  - BACKGROUND: Excessive upregulation of gastric epithelial cell apoptosis is
      speculated to be associated with ulcerogenesis in Helicobacter pylori-positive
      peptic ulcer disease. H. pylori may have an ulcerogenic effect through induction
      of gastric epithelial cell apoptosis mediated by infiltrating T cells and their
      soluble products. METHODS: The contents of soluble Fas ligand (sFasL) and
      interferon-gamma (IFN-gamma) in organ cultures and the degree of apoptosis and
      the expression of apoptosis-related proteins in the gastric epithelium were
      examined using the mucosal tissues obtained from the antrum and the ulcer site in
      patients with H. pylori-positive gastric ulcer (GU). The molecular mechanisms of
      gastric epithelial cell apoptosis induced by sFasL and IFN-gamma were analyzed
      using epithelial cell lines, MKN 45 and KATO III. RESULTS: The mucosal tissues of
      the ulcer site had substantially higher contents of sFasL and IFN-gamma in organ
      cultures regardless of its healing stage in association with increased numbers of
      apoptotic cells and enhanced expression of proapoptotic proteins Bak and Bax in
      the surface foveolar epithelium as compared with the antral tissues in patients
      with H. pylori-positive GU. The addition of sFasL caused increases in cytotoxic
      cell death and caspase-3 activation in MKN 45 and KATO III cells in which IFN
      gamma treated cells had more prominent effects than untreated cells. The
      expression of Bak in MKN 45 cells increased when they were treated with IFN
      gamma. CONCLUSIONS: Upregulation of mucosal sFasL and IFN-gamma may be involved
      in ulcerogenesis in patients with H. pylori-positive GU through induction of
      gastric epithelial cell apoptosis.

PMID- 12059050
TI  - Performance of two immunosorbent assay kits for the detection of serum
      immunoglobulin G to Helicobacter pylori in untreated greek patients.
AB  - BACKGROUND: The performance of serological methods used to detect Helicobacter
      pylori varies with the ethnicity and prevalence of the infection in the
      community. We have prospectively evaluated the performance of two commercially
      available serum enzyme immunoassays (EIA) detecting H. pylori immunoglobulin G
      (IgG) antibodies in the sera of untreated Greek patients. METHODS: One-hundred
      and-thirty consecutive untreated dyspeptic patients underwent endoscopy with
      biopsies from the gastric body (n = 2) and antrum (n = 2). Serum samples were
      also obtained from each patient. Serum H. pylori IgG antibody titres were
      determined with two EIA kits (Pyloriset EIA-G and Milenia H. pylori IgG).
      Sensitivities, specificities and optimal cut-off values of serum EIAs were
      determined for the population under investigation by using receiver operating
      characteristic (ROC) curve analysis and histology as gold standard. RESULTS:
      Ninety-seven patients were defined H. pylori-positive and 33 negative by
      histology. ROC curve analysis for the Pyloriset kit yielded 86% (95% CI, 78%-92%)
      sensitivity and 85% (68%-95%) specificity at an optimal cut-off value of >358
      units/ml. The respective values for the Milenia kit were 86% (78%-92%) and 82%
      (65%-93%) at an optimal cut-off value of >51 units/ml. The suggested cut-off
      values of the manufacturers for Pyloriset and Milenia kits are >300 and >44 EIA
      units, respectively, which yield 2% and 4% higher sensitivity, but 9% lower
      specificity for both EIA kits. CONCLUSIONS: Both serum EIA kits performed well in
      our study. Our data show that EIA cut-off values should be optimized for the
      population under investigation.

PMID- 12059051
TI  - Major differences in the IgG subclass response to Helicobacter pylori in the
      first and third worlds.
AB  - BACKGROUND: Studies in developed countries would suggest that the immune response
      to Helicobacter pylori infection is a T helper cell I predominant response.
      Unlike subjects from developed countries, those resident in developing countries
      are subject to infection with a myriad of gastrointestinal pathogens from early
      in life. Given that H. pylori is acquired early in life, such infections may
      alter the immune response to H. pylori. The aim of this study was to compare the
      immune response to H. pylori in subjects from developed and developing countries.
      METHODS: Using a previously validated IgG subclass ELISA, the H. pylori specific
      IgG I/IgG2 subclass ratio (a marker of the T helper cell response) in 58 adult
      and 21 paediatric symptomatic H. pylori positive Sowetan subjects was compared
      with that in 64 Australian and 45 German symptomatic H. pylori positive subjects.
      RESULTS: An IgGI predominant response (IgG1/IgG2 ratio >1) was observed in 81% of
      Sowetan adults and 90% of children compared with 4.7% of Australians and 4.4% of
      Germans. The IgG1/IgG2 ratio was significantly higher in Sowetans compared with
      Australians and Germans (P < 0.001). In Australian and German subjects the
      IgG1/IgG2 ratio was significantly higher in NUD compared with DU. No significant
      difference was observed between NUD and other disease states in Sowetans.
      CONCLUSIONS: This study is the first to provide evidence that the host immune
      response to H. pylori infection in an African population differs to that observed
      in subjects from developed countries. Further studies are required to determine
      if this occurs in other developing countries.

PMID- 12059052
TI  - Gastrectomized rats respond with exaggerated hypercalcemia to oral and
      intravenous calcium loads because of impaired ability of bone to take up Ca2+.
AB  - BACKGROUND: Gastrectomy (Gx) causes osteopenia. The hypothesis tested in the
      present study is that Gx affects Ca homeostasis and that an impaired ability to
      handle Ca contributes to the Gx-evoked osteopenia. METHODS: SHAM-operated and Gx
      rats were compared with respect to changes in blood Ca2+ after oral or
      intravenous loads of CaCl2 1-2 weeks or 2-4 months after the operations. RESULTS:
      Different doses of oral CaCl2 raised blood Ca2+ more in Gx than in SHAM rats,
      more so after 2-4 months than after 1-2 weeks. The rise was greater in fasted (48
      h) rats than in fed rats regardless of whether they were SHAM or Gx. While SHAM
      rats tolerated high doses of CaCl2 well, Gx rats died when exposed to quite
      modest doses, particularly 2-4 months after Gx. Intravenous infusion of CaCl2
      (2,500 micromol/kg/h) induced a greater and steeper rise in blood Ca2+ in Gx rats
      than in SHAM rats. Kinetic analysis of the blood Ca2+ data showed Gx rats to
      display: 1) a decreased Ca2+ elimination clearance from the central distribution
      compartment (blood), 2) a reduced size of the peripheral distribution compartment
      (the so-called bone fluid compartment). and 3) a spectacular decrease in the
      intercompartmental clearance (transfer of Ca2+ from blood to bone). These effects
      were notably apparent after 2-4 months. At sacrifice, the Gx-evoked osteopenia
      was confirmed by planimetric analysis of the calvariae. revealing 40% reduction
      of bone tissue after 2-4 months. CONCLUSIONS: Based on the present data we argue
      that Gx rats respond with exaggerated hypercalcemia to oral and intravenous CaCl2
      loads because of a greatly impaired transfer of Ca+ from blood to bone. We
      suggest that with time this impairment results in osteopenia.

PMID- 12059053
TI  - Tachykinin NK1 receptors mediate atropine-resistant net aboral propulsive
      complexes in porcine ileum.
AB  - BACKGROUND: We studied the effects of tachykinin receptor antagonists on fluid
      induced, spontaneous net aboral propulsive complexes in isolated, vascularly
      perfused porcine ileal segments. METHODS: Fluid was instilled at a constant rate
      into the proximal opening of the segment, resulting in regular, rapidly
      propagating propulsive complexes along the entire ileal segment in the aboral
      direction. RESULTS: NKI, NK2 or NK3 receptor antagonists (CP99994, SR48968 and SR
      142801 all at 10(-6) M) had no effect on the frequency of propulsive complexes.
      Atropine (10(-6) M) abolished the propulsive complexes for 15.0 +/- 1.3 min (n =
      18). In spite of continued atropine infusion, the propulsive complexes
      reappeared. Infusion of the NK1 receptor antagonist CP99994 (10(-6) M) during
      continued atropine infusion blocked net aboral propulsive complexes in 5
      experiments for 12.2 +/- 2.4 min and resulted in motor paralysis in 2
      experiments. SP release, measured in the venous effluent, was significantly
      increased in relation to propulsive complexes during atropine infusion.
      CONCLUSION: We conclude that, in the porcine ileum, tachykinins mediate atropine
      resistant net aboral propulsive complexes acting on NKI receptors.

PMID- 12059054
TI  - Mutational analysis of CD28 in coeliac disease.
AB  - BACKGROUND: Coeliac disease shows a strong genetic predisposition involving HLA
      DQ2 and non-HLA components. The CD28 cell surface molecule, encoded by CD28,
      represents a potential candidate coeliac disease susceptibility gene.
      Furthermore, some studies have demonstrated linkage to the CD28/CTLA4 gene
      region. To investigate whether germline mutations in CD28 contribute to coeliac
      disease susceptibility, we have carried out a comprehensive analysis of the gene
      in Swedish patients with biopsy-proven disease. METHODS: Blood samples were
      collected from 52 children with biopsy proven coeliac disease attending one
      Swedish centre. DNA was extracted from lymphocytes and all exons and intron-exon
      boundaries of CD28 were screened for mutations. Analysis of CD28 was undertaken
      by a combination of conformation specific gel electrophoresis and direct
      sequencing. RESULTS: Three sequence variants were identified: a synonymous G-->4A
      substitution at position 3 of codon 35 encoding alanine, a synonymous G-->A
      substitution at position 3 of codon 70 encoding glycine, and a T-->C substitution
      at nucleotide +17 of intron 3. No pathogenic variants were detected. CONCLUSIONS:
      There is no evidence from this study that mutations in CD28, which lead to an
      altered protein, contribute to coeliac disease susceptibility.

PMID- 12059055
TI  - Incidence of inflammatory bowel disease in children in southeastern Norway: a
      prospective population-based study 1990-94.
AB  - BACKGROUND: Most incidence studies of ulcerative colitis (UC) and Crohn disease
      (CD) have dealt with adults and there are have been few population-based
      prospective studies of the incidence of inflammatory bowel disease (IBD) in
      children. The aim of this study was to determine the incidence after re
      evaluation of the diagnosis of UC and CD in childhood and adolescence in a
      prospective population-based survey. METHODS: From 1 January 1990 to 31 December
      1993, all newly diagnosed patients with UC and CD under the age of 16 years were
      registered. On 1 January 1992 there were 174,482 children in the study
      population. The diagnosis was based on internationally accepted criteria and all
      clinical data were reviewed by two gastroenterologists independently of each
      other. All patients were subjected to a second evaluation 1 year after inclusion
      in the study. Patients initially diagnosed as indeterminate colitis (IND) were
      also reassessed. RESULTS: A total of 14 cases of UC, 13 cases of CD and 2 cases
      of IND were registered during the study period. At re-evaluation of the two
      patients diagnosed as IND, one was reclassified as having UC and one as having
      CD. This yielded a mean annual incidence of 2.14 (95% CI 1.20-3.54) per 100,000
      for UC and 2.00 (95% CI 1.10-3.36) per 100,000 for CD. The male:female ratio in
      UC was 4.0 and 1.8 in CD. Median time interval from onset of symptoms to
      diagnosis was 4 months for UC and 5 months for CD. A high proportion of the
      children with UC (80%; 12/15) had extensive colitis. Four patients with CD had a
      first-degree relative with IBD. CONCLUSION: This study does not support an
      increased incidence of paediatric CD over the past decade. The incidence of
      paediatric UC seems to have remained stable over the past 30 years. In the CD
      group, we find a high incidence of IBD in first-degree relatives.

PMID- 12059056
TI  - Increased expression of inducible nitric oxide synthase in circulating monocytes
      from patients with active inflammatory bowel disease.
AB  - BACKGROUND: Inducible nitric oxide synthase (iNOS) expression and nitric oxide
      (NO) synthesis are increased in epithelial cells and in tissue macrophages of the
      inflamed mucosa from patients with inflammatory bowel disease (IBD). Since tissue
      macrophages are derived from circulating monocytes, we studied iNOS expression in
      circulating monocytes and related this expression to disease activity. In view of
      the possible role of NO in monocyte function, we also studied iNOS expression in
      relation to markers of monocyte activation. METHODS: The expression of iNOS in
      circulating monocytes from 15 patients with active IBD, 6 patients who went into
      remission and 18 healthy controls was quantified by flow cytometry and correlated
      with surface markers (CD63, CD11b, HLA-DR) for monocyte activation. In addition,
      iNOS expression in circulating monocytes was assessed by Western blotting,
      immunocytochemistry and measurement of the NO metabolites nitrite and nitrate in
      plasma. RESULTS: The expression of iNOS in circulating monocytes and the
      percentage of iNOS-positive monocytes were increased in patients with active IBD
      compared to healthy controls (fluorescence index: 1.3 (0.1-6.3) versus 0.8 (0.0
      1.8); P < 0.05: percentage of iNOS positive monocytes: 37.3 (1.0-77.0)% versus
      5.3 (0.0-43.3)%; P<0.01). The six patients who went into remission all had a
      marked reduction of iNOS expression. iNOS expression was confirmed by Western
      blotting and immunocytochemistry. Plasma nitrite and nitrate levels were elevated
      in three patients with active 1BD. The surface markers for monocyte activation,
      CD63 and CD11b, were not elevated. HLA-DR expression was decreased on circulating
      monocytes from patients with active ulcerative colitis. CONCLUSIONS: iNOS is
      increased in circulating monocytes from patients with active IBD and this
      increased expression correlates with disease activity. Considering the decreased
      HLA-DR expression and absence of monocyte activation markers, NO produced by iNOS
      may have a function in suppressing systemic monocyte activation.

PMID- 12059057
TI  - The role of mast cells in the development of 2, 4, 6-trinitrobenzene sulfonic
      acid-induced colitis in rats.
AB  - BACKGROUND: The role of mast cells in Crohn disease (CD) remains to be
      established. The aim of this study was to elucidate this in the development of CD
      like colitis in rats by the use of mast-cell-deficient Ws/Ws and their control
      W+/W+ rats. METHODS: CD-like colitis was induced in both groups by an enema of 10
      mg of 2,4, 6-trinitrobenzene sulfonic acid (TNBS) in 50% ethanol. Colonic damage,
      adhesion and colonic weight were measured at 7 and 14 days after the TNBS/ethanol
      enema. Rat mast cell protease-2 (RMCP-2) in the colonic tissue was also measured
      at 7 days after the enema. RESULTS: There was no significant difference between
      W+/W+ and Ws/Ws rats in terms of colonic damage, adhesion or colonic weight. The
      tissue content of RMCP-2 in Ws/Ws rats treated with either saline or TNBS/ethanol
      was only maintained at a much lower level than that in W+/W+ rats with the
      corresponding treatment. CONCLUSIONS: These results demonstrate that mast cells
      are not essential in the development of 2, 4, 6-trinitrobenzene sulfonic acid
      induced colitis in rats.

PMID- 12059058
TI  - Changing patterns of gastric carcinoma over the past two decades in a single
      institution: clinicopathological findings in 1557 patients.
AB  - BACKGROUND: Reported differences in clinicopathological patterns of gastric
      carcinoma (GC) suggest the presence of time-related changes of cancer biology.
      The aim of this study was to analyse any fluctuations of GC biology in a large
      series of patients from Poland, where morbidity and mortality rates for GC are
      relatively high. METHODS: Based on the prospectively collected data of 1557 GC
      patients treated surgically between 1977 and 1999, we analysed the differences in
      clinicopathological patterns for two consecutive periods: 1977-88 (group I) and
      1989-99 (group II). Moreover, time-related trends of GC biology were assessed.
      RESULTS: The mean age of the patients was 59.1 years (range 20-93) and increased
      from 58.1 years in group I to 59.9 years in group II (P < 0.05). Early GC
      occurred in 6.2% of cases in group I and in 13.7% in group II (P < 0.001). The
      incidence of stage IV carcinomas according to the UICC classification
      significantly decreased from 70.9% to 53.6% (P < 0.001). The proportion of
      tumours located in the distal part of the stomach declined from 44.1% in group I
      to 37.6% in group II (P < 0.05). Analysis did not reveal differences in
      histological type (according to the Lauren classification) between groups;
      nevertheless, a significant trend toward lowering incidence of intestinal type GC
      was observed (P < 0.05). Overall, 5-year survival was 27.2% and increased over
      the period of study from 18.6% to 30.4% (P < 0.001). CONCLUSIONS: The patterns of
      GC stage, location and histology have changed during the analysed period of time.
      Observed differences are probably related to fluctuations in carcinogenic factors
      and have diagnostic as well as therapeutic implications.

PMID- 12059059
TI  - Design, organization and management of a controlled population screening study
      for detection of colorectal neoplasia: attendance rates in the NORCCAP study
      (Norwegian Colorectal Cancer Prevention).
AB  - BACKGROUND: In the past three decades, the incidence of colorectal cancer (CRC)
      in Norway has doubled, surpassing all other Nordic countries for both men and
      women to become the most frequently diagnosed cancer. A small-scale, randomized
      study on flexible sigmoidoscopy (FS) screening in Telemark, Norway, has shown a
      reduction in accumulated CRC incidence after 13 years. The aim of our study was
      to evaluate the effect on CRC mortality and morbidity by screen detection of CRC
      and removal of precursor lesions (polypectomy), and to test out the management
      and organization mimicking a countrywide screening service. A total of 13,823 men
      and women (1:1), age 55-64 years, were drawn randomly from the population
      registries in Oslo (urban) and the county of Telemark (mixed urban and rural) and
      invited to have a screening examination. The rest of the relevant age cohorts
      constituted the control groups. In the screening group, 535 individuals were
      excluded according to exclusion criteria, rendering 13,288 individuals eligible
      for screening examination. METHODS: A once only screening model was used. In the
      screening group, individuals were randomized to have a once only FS or a
      combination of FS and faecal occult blood test (FOBT). RESULTS: The overall
      attendance rate was 8,849 out of 13,288 (67%); 73% in Telemark and 60% in Oslo.
      Attendance for FS only was 68% and 65% for combined FS&FOBT. CONCLUSIONS: The
      present FSIFS&FOBT screening study obtained a high acceptance rate for both
      screening modalities. The attendance rate was stable throughout the trial,
      suggesting an acceptable model for management of future countrywide screening.

PMID- 12059060
TI  - No support for endoscopic surveillance for gastric cancer in hereditary non
      polyposis colorectal cancer.
AB  - BACKGROUND: The DNA mismatch repair gene mutations underlying hereditary non
      polyposis colorectal cancer syndrome (HNPCC) also predispose, besides colorectal
      and endometrial cancer, to gastric cancer. usually of the intestinal type. The
      carcinogenetic pathway behind the elevated gastric cancer risk is largely
      unknown. METHODS: The aim of this study was to determine whether there are any
      premalignant lesions to search for in gastric surveillance in HNPCC by comparing
      gastric histopathology between mutation-positive and mutation-negative family
      members. We searched for differences in occurrence of Helicobacter pylori,
      inflammation, atrophy, intestinal metaplasia and dysplastic changes. Upper
      gastrointestinal endoscopy was performed for 73 mutation-positive and 32 mutation
      negative family members. RESULTS: One case of duodenal cancer was detected in the
      mutation-positive group, but no gastric neoplastic lesions were seen in either
      group. There were no differences in the occurrence of polyps, H. pylori,
      inflammation, activity, atrophy nor intestinal metaplasia tested with binaric,
      logistic, regression analysis. CONCLUSIONS: We conclude that surveillance
      gastroscopy may not be beneficial in HNPCC, since neither cases of early cancer
      nor premalignant lesions could be detected in our series of 73 mutation-positive
      subjects.

PMID- 12059061
TI  - Localization of hepatitis C virus RNA on human erythrocytes by RT in situ PCR
      technique.
AB  - BACKGROUND: Our previous results showed that hepatitis C virus (HCV) is
      detectable on erythrocytes by RT in situ PCR. The aims of the present study were
      to compare the sensitivity of this erythrocyte in situ PCR to routine serum
      solution phase HCV PCR as well as to obtain more data about the binding and
      cellular localization of HCV in the erythrocyte. METHODS: 105 previously HCV
      infected patients and 20 control individuals were studied using RT in situ PCR on
      erythrocytes and solution phase RT-PCR from serum samples. Binding of HCV to
      erythrocytes was studied by in vitro inoculation. RT in situ PCR results were
      evaluated by fluorescence and confocal laser scanning microscopy. RESULTS: From
      105 HCV cases, 78 gave positive, while 5-and all control cases-gave negative
      results by both PCR techniques. In 21 cases, only the in situ technique provided
      positive results, while in only I case did the solution phase method provide
      positive results. During in vitro inoculation, an early HCV-erythrocyte binding
      was detected followed by virus internalization. CONCLUSIONS: Erythrocyte-in situ
      PCR was found to show higher sensitivity for the detection of HCV compared to the
      generally applied serum PCR method. In vitro studies suggested a specific binding
      of HCV to erythrocyte and showed the virus to be capable of internalization.

PMID- 12059062
TI  - Cholestatic effect of large bilirubin loads and cholestasis protection conferred
      by cholic acid co-infusion: a molecular and ultrastructural study.
AB  - BACKGROUND: Large intravenous bilirubin loads block biliary phospholipid
      secretion, produce canalicular membrane lesions and cause canalicular
      cholestasis. Cholic acid co-infusion forestalls these untoward effects. The aim
      of this study was first to determine whether bilirubin overload causes
      cholestasis through reducing the activity or the hepatic expression of the bile
      salt export pump (bsep) or Na-taurocholate co-transporting polypeptide (ntcp)
      and, secondly, whether cholic acid co-infusion forestalls cholestasis by
      upregulating bsep, ntcp or phosphoglycoprotein 3 (pgp3) expressions or
      activities. A further aim was to determine whether large bilirubin infusions also
      produce ultrastructural changes inside hepatocytes. METHODS: The effects of
      intravenous infusion of 2 g bilirubin over 150 min on hepatic expression of bsep,
      ntcp and pgp3 were studied in bile acid-depleted and cholic acid co-infused pigs,
      and related to canalicular bile acid transport and bile secretion. Effects on
      hepatocyte ultrastructural morphology were analysed by electron microscopy.
      RESULTS: Bilirubin-induced cholestasis reflected marked diminution of bsep and
      pgp3 transport activities and not reduced hepatic expression of these
      transporters. Hepatocyte ultrastructural abnormalities were predominantly
      confined to the hepatocyte canalicular membrane in cholestatic livers. Cholic
      acid co-infusion with bilirubin conferred complete cholestasis protection through
      enhancing pgp3 and bsep transporter activities and not through upregulating their
      expression. Bilirubin infusion did not change ntcp expression. CONCLUSION:
      Bilirubin-induced cholestasis is due to markedly impaired activity of the
      membrane-embedded bsep transporter consequent upon ultrastructural injury to the
      canalicular membrane. Cholic acid co-infusion with bilirubin enhances bsep and
      pgp3 activities and confers protection against canalicular membrane injury and
      bilirubin-induced cholestasis.

PMID- 12059063
TI  - Are modified procedures significantly better than conventional procedures in
      percutaneous transhepatic treatment for complicated right hepatolithiasis with
      intrahepatic biliary strictures?
AB  - BACKGROUND: Conventional percutaneous procedures for treating patients with
      recurrent hepatolithiasis associated with complicated intrahepatic biliary
      strictures require multiple dilation sessions before stone extraction. We
      modified the approach, reducing the number of dilation sessions required and
      using newer lithotripsy and irrigation methods. We suggest that the modified
      procedures are superior to conventional management and demonstrate their utility
      in clearing hepatolithiasis. METHODS: Percutaneous transhepatic stricture
      dilation and cholangioscopic lithotripsy were performed to treat patients with
      right recurrent hepatolithiasis with complicated intrahepatic biliary strictures.
      Conventional methods were used in 40 patients (Group A). Modified methods,
      including simplification of tract establishment and stricture dilation and
      electrohydraulic lithotripsy (EHL) were used in 60 patients (Group B). RESULTS:
      Group B patients had fewer complications (massive hemobilia: 0% versus 15%, P =
      0.0032, cholangitis: 0% versus 17.5%, P=0.0012), tolerated the procedures better
      (intolerable pain: 0% versus 12.5%, P=0.0087), had a higher rate of success
      (residual stones: 3.3% versus 20%, P=0.0132; remaining asymptomatic and stone
      free: 81% versus 50%, P = 0.0021), a shorter hospital stay (17.8 +/- 4.4 days
      versus 36.2 +/- 5.5 days, P < 0.001) and lower overall expense (USD 2689 versus
      USD 3848) than Group A patients. CONCLUSION: We believe that the modified methods
      are superior to conventional treatment in that they effectively decrease
      procedural complications and cost, and significantly improve treatment results.

PMID- 12059064
TI  - Can sedation reduce the cardiac stress during gastrointestinal endoscopy? A study
      with non-invasive automated cardiac flow measurement by color Doppler
      echocardiography.
AB  - BACKGROUND: Upper gastrointestinal endoscopy (UGIE) may cause some cardiac
      stress. The effect of sedation on hemodynamics during UGIE has not been fully
      studied, and therefore the aim of this study was to clarify whether or not
      sedation can reduce cardiac stress dufing UGIE. METHODS: Eight normal male
      volunteers undergoing UGIE with sedation (0.1 mg/kg of midazolam) and without it
      (two endoscopies per volunteer in random order) were monitored throughout the
      procedure by means of electrocardiogram, blood pressure and peripheral oxygen
      saturation (SpO2). Cardiac output was measured at six points before, during and
      after endoscopy from automated cardiac flow measurement by color Doppler
      echocardiography. Serum norepinephrine, epinephrine, dopamine and ACTH
      concentrations were measured before and after the examination. RESULTS: No
      significant differences in heart rate, systolic blood pressure, rate-pressure
      product, cardiac output and left ventricular work index were observed between the
      sedated and non-sedated groups. SpO2 hardly changed during endoscopy in the non
      sedated group, but decreased slightly in the sedated group (P = 0.075). Although
      all serum catecholamine concentration changes were within normal limits in both
      groups, after endoscopy only epinephrine concentration was significantly lower in
      the sedated group than in the non-sedated group (P = 0.0027). CONCLUSIONS:
      Conscious sedation with midazolam does not reduce the cardiac stress during UGIE.

PMID- 12059065
TI  - Preoperative assessment of gastric cancer vascularity by flash echo imaging.
AB  - BACKGROUND: Tumor vascularity as indicated by immunohistochemical staining is a
      significant prognostic factor in gastric and other cancers. Non-invasive
      preoperative assessment of the vascularity of gastric cancers has not been
      possible. We aim to determine the reliability of harmonic flash echo imaging
      (FEI) for assessment of vascularity of gastric cancers by comparison with CD34
      staining of resected specimens. METHODS: Twelve patients undergoing surgical
      resection of advanced gastric cancer were studied. An ultrasound system
      transmitting ultrasound pulses at 2.3 MHz and receiving them at 4.6 MHz (second
      harmonic image) was used for harmonic FEI. Approximately 30 s after intravenous
      injection of ultrasonic contrast medium (SHU 508A, Levovist), second harmonics
      (4.6 MHz) emitted from microbubbles were obtained to enhance the B-mode images.
      Using the tumor image showing strongest enhancement in each FEI series, regions
      of interest were determined to measure mean echo intensity in the tumor.
      Immunohistochemistry using antibodies against CD34 was carried out in resected
      specimens. Tumor vascularity was determined by counting stained microvessels.
      RESULTS: A significant positive correlation was noted between sonographic
      amplitude determined preoperatively by FEI analysis and number of CD34-stained
      microvessels in tumor specimens (r = 0.869, P = 0.004). CONCLUSION: Vascularity
      of gastric cancers now can be evaluated non-invasively by harmonic FEI.

PMID- 12059066
TI  - Long-term endoscopic remission of crohn disease after autologous stem cell
      transplantation for acute myeloid leukaemia.
AB  - A favourable course of Crohn disease has been observed after allogeneic bone
      marrow transplantation. and there is now mounting evidence that autologous stem
      cell may be an effective treatment for severe autoimmune diseases. Here, we
      present the first long-term endoscopic follow-up of a patient with Crohn disease
      undergoing autologous stem cell transplantation for haematological disease. A 54
      year-old woman developed Crohn disease and was submitted to ileocaecal resection.
      Four months after surgery, the patient contracted acute myeloid leukaemia. She
      was initially treated with chemotherapy, and subsequently underwent autologous
      stem cell transplantation. Following transplantation, the patient has remained in
      clinical remission regarding both diseases, without anti-inflammatory medication.
      She has undergone ileo-colonoscopy with normal findings at 1, 2, 3 and 5 years
      after transplantation. This case suggests that autologous stem cell
      transplantation can change not only the clinical course, but also the natural
      history of intestinal inflammation in Crohn disease. This has pathophysiological
      as well as therapeutic implications.

PMID- 12059067
TI  - Treatment of non-ulcer dyspepsia: are prokinetics effective?

PMID- 12059068
TI  - Successful endoscopic band ligation of duodenal Dieulafoy's lesions. Further
      large controlled studies are required.

PMID- 12059069
TI  - Fecal elastase-1 as a test for pancreatic function: a review.
AB  - Pancreatic elastase-1 is a specific human protease synthetized by the acinar
      cells. Immunoreactive elastase-1 cannot be detected in either porcine or bovine
      pancreatic enzyme preparations. It is very stable and, in contrast to fecal
      chymotrypsin, elastase is unaffected by exogenous pancreatic enzyme treatment,
      and correlates well with exocrine pancreatic function tests. The measurement of
      this proteolytic enzyme in stool by means of an enzyme-linked immunosorbent assay
      (ELISA) is a sensitive, specific, and relatively inexpensive non-invasive test.
      It is an accurate function test for patients with chronic pancreatitis confirmed
      by endoscopic retrograde cholangiopancreatography and computerized axial
      tomography. It shows higher sensitivity and specificity for exocrine pancreatic
      insufficiency than fecal chymotrypsin determination and is comparable to oral
      pancreatic function tests such as the pancreolauryl test.

PMID- 12059070
TI  - Alpha2-macroglobulin deletion polymorphism and plasma levels in late onset
      Alzheimer's disease.
AB  - The acute-phase "panproteinase" inhibitor alpha2-macroglobulin (alpha2M), a
      protein involved in inflammatory reactions, has been identified in amyloid
      plaques in Alzheimer's disease (AD). In addition, alpha2M is involved in AD
      susceptibility at the genetic level, and a deletion polymorphism at the a2M gene
      has been found to be associated with sporadic AD. We analyzed the deletion
      polymorphism and alpha2M plasma levels in 93 ultraoctuagenarian patients with
      late-onset sporadic AD and in controls (n=157). alpha2M allele frequencies did
      not differ between AD patients (alpha2M*2=0.169) and controls (alpha2M*2=0.146).
      The mean plasma concentrations of alpha2M were similar in patients (271.8+/-79
      mg/dl) and controls (269.5+/-81.2 mg/dl). No difference was found in the alpha2M
      mean plasma levels associated with the three alpha2M genotypes, indicating that
      the deletion has no effect on alpha2M protein level. However, in AD patients
      alpha2M mean plasma values differed significantly according to apolipoprotein E
      genotypes (p=0.03), with E3/E3 homozygotes showing the highest levels. Since in a
      previous work E3/E3 were found to be associated with the highest plasma levels of
      alpha1-antichymotrypsin, another acute-phase protein, the present findings seem
      to support the hypothesis that inflammation may be a relevant factor in AD
      pathogenesis peculiar to E3/E3 subjects.

PMID- 12059071
TI  - High-speed detection of the two common paraoxonase polymorphisms Leu55-->Met and
      Gln192-->Arg by real-time fluorescence PCR and melting curves.
AB  - Human paraoxonase (PON1) is a calcium-dependent esterase exclusively bound to
      apolipoprotein A-I and clusterin, containing high-density lipoprotein (HDL)
      particles that hydrolyzes organophosphates and aryl esters. Several studies have
      indicated that PON1 can prevent low-density lipoprotein (LDL) oxidation by
      hydrolyzing lipid peroxides in the lipoprotein, which is the crucial first step
      for atherogenesis. Therefore it may protect against the development of
      atherosclerosis. Serum PON1 activity has been shown to be decreased in familiar
      hypercholesterolemia and in diseases that are associated with accelerated
      atherogenesis. The PON1 gene has two common coding region polymorphisms, Leu55-
      >Met and Gln192-->Arg. Both polymorphisms have been identified as independent
      risk factors for cardiovascular disease in diabetic and non-diabetic patients. We
      have established high-speed and easy-to-perform genotyping for the two most
      significant PON1 gene polymorphisms, employing the LightCycler technology and
      melting curves. This technique eliminates PCR contamination related to sample
      handling and does not require digestion of PCR products with restriction enzymes
      and/or fragment separation on gels.

PMID- 12059072
TI  - Rapid detection of polymorphisms of the nitric oxide cascade.
AB  - NOS3 (endothelial nitric oxide (NO) synthase) and p22phox (subunit of NAD(P)H
      oxidase) are two genes whose products are involved in formation and degradation
      of NO, a ubiquitous signaling molecule largely responsible for the maintenance of
      normal endothelial function. The G894T polymorphism of NOS3 and the C242T
      polymorphism of p22phox are reportedly associated with numerous cardiovascular
      diseases. For each polymorphism we developed a rapid and reliable method with the
      hybridization probes format on the LightCycler and compared it with conventional
      PCR-restriction fragment length polymorphism (PCR-RFLP) analysis with regard to
      reliability, duration and cost. The new methods are more reliable, faster and
      less expensive than PCR-RFLP analysis and therefore represent a significant
      advantage in the detection of two candidate risk factors for cardiovascular
      diseases.

PMID- 12059073
TI  - Salivary electrolyte concentrations are associated with cystic fibrosis
      transmembrane regulator genotypes.
AB  - It is estimated that about one in 24 Belgian Caucasians is a cystic fibrosis (CF)
      heterozygote. Until now, CF heterozygotes can only be identified by genetic
      decoding (e.g. Inno-Lipa CF2 test), as they cannot be phenotypically
      distinguished from the general population. The aim of this study was to evaluate
      differences in salivary electrolyte concentrations (calcium, bicarbonate,
      chloride, potassium, sodium and phosphate) and salivary osmolarity between CF
      homozygotes (n=41), CF heterozygotes (n=56) and healthy controls (n=65).
      Differences between the three groups were investigated by means of non-parametric
      tests. Several significant differences between the three study groups and among,
      as well as between, the different cystic fibrosis transmembrane regulator (CFTR)
      genotypes were observed. Significant differences in salivary electrolyte
      concentrations between individuals with delta F508 mutation and those without,
      and between CF homozygotes and heterozygotes were observed. The concentrations of
      several salivary electrolytes, and salivary osmolarity were significantly higher
      in CFTR genotype individuals. Differences in salivary electrolyte concentrations
      may partly explain differences in caries between the three study groups.

PMID- 12059074
TI  - Granulocyte-colony stimulating factor (G-CSF) and macrophagecolony stimulating
      factor (M-CSF) in colorectal cancer patients.
AB  - We have investigated the serum level of granulocytecolony stimulating factor (G
      CSF) and macrophagecolony stimulating factor (M-CSF) and the commonly accepted
      tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19
      9 (CA 19-9) in colorectal cancer. Additionally, we have defined the diagnostic
      sensitivity, specificity, positive predictive value, negative predictive value
      and receiver-operating characteristics (ROC) curve for G-CSF and M-CSF. The serum
      levels of cytokines were measured in 49 patients with colorectal cancer and in 40
      healthy subjects. G-CSF and M-CSF were determined using enzyme-linked
      immunosorbent assay (ELISA). CEA and CA 19-9 were measured by microparticle
      enzyme immunoassay. There were significant increases in the level of circulating
      G-CSF and M-CSF in the colorectal cancer patients compared to the control group.
      Moreover, the diagnostic sensitivity of M-CSF was higher (65%) than the
      sensitivity of CEA (31%) and CA 19-9 (20%). The diagnostic specificities of M-CSF
      and G-CSF were 95%, and the M-CSF predictive value was higher compared with the
      predictive value of G-CSF. These results suggest a potential role for M-CSF as a
      tumor marker for colorectal cancer.

PMID- 12059075
TI  - Sialic acid, intercellular adhesion molecule-1 and rheumatoid arthritis: a study
      on the erythrocyte membrane.
AB  - We measured serum levels of soluble intercellular adhesion molecule-1 and
      erythrocyte membrane sialic acid in patients with rheumatoid arthritis and
      studied their correlation with the disease activity. Serum soluble intercellular
      adhesion molecule-1 level was determined with sandwich ELISA and sialic acid
      level with the method of Shamberger in 42 patients with rheumatoid arthritis and
      in 30 healthy controls. Significantly lower erythrocyte membrane sialic acid and
      higher serum levels of soluble intercellular adhesion molecule-1 were found in
      patients with rheumatoid arthritis compared with healthy controls (p<0.001 for
      both). Significant negative correlation between soluble intercellular adhesion
      molecule-1 level and erythrocyte membrane sialic acid concentration (r=-0.49,
      p<0.001) and positive correlations between soluble intercellular adhesion
      molecule-1 level and Ritche Articular Index score and C-reactive protein (r=0.32,
      p<0.05; r=0.44, p<0.01, respectively) were observed. From these data we conclude
      that decreases in erythrocyte membrane sialic acid concentration and increases in
      soluble intercellular adhesion molecule-1, erythrocyte sedimentation rate and C
      reactive protein levels are present in rheumatoid arthritis, and that the
      increased soluble intercellular adhesion molecule-1 in rheumatoid arthritis might
      be due to the decreased erythrocyte membrane sialic acid concentration. The
      levels of soluble intercellular adhesion molecule-1 may be a novel marker for the
      disease status and the activity of rheumatoid arthritis.

PMID- 12059076
TI  - Determination of organochlorine pesticide residues in the blood of healthy
      individuals.
AB  - Pesticide use is one of several factors that have permitted maintenance of our
      supply of food in spite of continuing increase of the population. However, the
      use of biologically active compounds poses potential problems of toxicity. If the
      compound is used at any stage of food production, residues or derivatives may
      persist in food and the entire population may be exposed to the trace amounts of
      the material. The human body burden associated with long-term exposure may or may
      not be associated with illness. Persistent environmental contaminants such as
      pesticide residues have long been suspected to be implicated in cancer etiology.
      Organochlorine chemicals are persistent, lipophilic compounds commonly present in
      the environment. Some of them demonstrated carcinogenic activity in laboratory
      animals. Controversy still exists concerning their carcinogenic potential in
      humans. To answer this question, clinical toxicology laboratories should propose
      validated methodologies able to identify and quantify pesticide residues in
      biological samples. An example of chromatographic method dedicated to
      organochlorine residues is presented here and illustrated by results obtained in
      a healthy population (104 men, 147 women). Only 17.9% of the samples were free
      from detectable amounts of pesticides and p,p'-DDE 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene was the most frequently detected residue (66.5%).
      Hexachlorobenzene was found at detectable level in 13.5% of the samples.

PMID- 12059077
TI  - Reference values for a heterogeneous ferritin assay and traceability to the 3rd
      International Recombinant Standard for Ferritin (NIBSC code 94/572).
AB  - Reference values for Ferritin Flex on the Dimension RxL analyzer calibrated
      against the 3rd International Standard for Ferritin (recombinant) and N-Latex
      Ferritin on the BNA II nephelometer calibrated against the 2nd International
      Standard for Ferritin (spleen) both from Dade Behring (Marburg, Germany) were
      established (77 men and 182 women). Exclusion criteria were iron deficiency or
      iron deficiency anemia, inflammation, liver disease, malignancy, and other
      hematological or chronic disorders. The reference values (5.0th-95th percentiles)
      were as follow: for N-Latex Ferritin - men, 12-399 microg/l; women <50 years, 11
      102 microg/l and women > or =50 years, 17-219 microg/l; for Ferritin Flex - men,
      14-415 microg/l; women <50 years, 11-111 microg/l and women > or =50 years, 22
      224 microg/l. Both assays correlated very closely with each other (r=0.993). The
      linearity was acceptable down to 2 microg/l for the Ferritin Flex method, but
      only down to 15 microg/l for the N-Latex Ferritin assay. The mean recovery of the
      3rd International Standard by N-Latex Ferritin and Ferritin Flex was comparable
      (approximately 80%). We conclude that the new Ferritin Flex assay, which is based
      on the new 3rd International Standard, should be used for ferritin measurement in
      the routine medical laboratories in the future.

PMID- 12059078
TI  - The circulating levels of cardiac natriuretic hormones in healthy adults: effects
      of age and sex.
AB  - In order to study the relationships between sex hormones, aging, and circulating
      levels of cardiac natriuretic peptides and to define reference values for atrial
      natriuretic peptide (ANP) and brain natriuretic peptide (BNP) assays, we measured
      the plasma levels of cardiac natriuretic peptides in a large group of healthy
      adults divided according to age and sex. We studied 216 healthy subjects of both
      sexes (109 men and 107 women) with age ranging from 20 to 77 years (mean 43.2+/
      14.8 years). All subjects were non-obese and had normal arterial blood pressure;
      they were free from acute diseases, including asymptomatic heart disease. Highly
      sensitive and specific IRMA methods were used to measure plasma ANP and BNP. The
      mean ANP value in healthy adult subjects of both sexes was 17.8+/-10.9 pg/ml with
      no significant difference between men (16.7+/-10.0 pg/ml) and women (18.8+/-11.7
      pg/ml). The mean BNP value in healthy adult subjects of both sexes was 9.9+/-9.0
      pg/ml with a significant difference (p<0.0001) between men (7.7+/-7.1 pg/ml) and
      women (12.2+/-10.2 pg/ml). There was a weak linear relationship between age and
      either ANP (r=0.350, p<0.0001) or BNP (r=0.254, p=0.0002) values. When the
      circulating levels of cardiac natriuretic hormones, and age and sex were analyzed
      by multiple stepwise regression analysis, both age and sex significantly and
      independently contributed to the regression. Our study indicates independent
      positive effects of aging and female sex hormones on ANP and BNP levels in
      healthy adult subjects. These effects should be taken into account in the
      calculation of appropriate reference values for cardiac natriuretic hormones.

PMID- 12059079
TI  - Plasma free amino acids in Taiwan Chinese: the effect of age.
AB  - Values of plasma amino acids (AA) in Taiwan Chinese in different age groups were
      determined. AA analysis was performed by ion-exchange chromatography. The results
      correlated well with the reference values published by Shapira in 1989,
      indicating that plasma AA concentrations are not evidently affected by race and
      dietary habits. We also confirmed the effect of age on plasma free AA levels.
      More than two thirds of 35 amino acids showed statistically significant
      differences between age groups (p<0.05, one-way ANOVA test). Levels of taurine,
      hydroxyproline, threonine, serine, glutamic acid, proline, citrulline and alpha
      amino-eta-butyric acid varied with age (p<0.01). Only a few AA, including alpha
      amino-adipic acid, glycine, alanine, cystine, homocystine, isoleucine, tyrosine,
      gamma-aminobutyric acid and tryptophan, showed no statistically significant
      differences between the different age groups. When comparing the mean differences
      in individual AA among these three age groups using the post-hoc test, alanine,
      tyrosine, phenylalanine, glycine, glutamine, cystine, homocystine, isoleucine,
      gamma-aminobutyric acid and tryptophan appeared to be constant across all age
      groups. Glutamic acid and serine correlated significantly with age (p<0.05), with
      a definite decline in concentration from infancy to adulthood (r=0.396 and 0.243;
      p<0.01, respectively). We conclude that AA values are not evidently affected by
      race, but they do vary with age.

PMID- 12059080
TI  - Regression-based reference limits for urinary amino acids in a pediatric
      population.
AB  - Age-related variation of the urinary excretion of amino acids has been widely
      reported. Instead of the conventional reference intervals, continuous reference
      limits might be a more practical approach during periods of rapid changes such as
      infancy or childhood. Regression-based reference limits have been produced for
      the urinary excretion of 23 amino acids analyzed in 148 healthy individuals from
      0 to 12 years of age. Urinary excretion was modeled as a function of age by two
      parametric procedures: the polynomial and the piece-wise linear regression
      methods. Likewise, age-specific standard deviation was estimated by the
      regression of the absolute values of the residuals on age. Residual analysis was
      employed to select the best-fitting model and the 95% reference limits, and their
      95% confidence intervals were calculated and plotted against the raw data. The
      urinary excretion of 19 amino acids decreased rapidly during the first year of
      life with a further slow decline thereafter. These amino acids fit better the
      piecewise model. The other four amino acids displayed a steady decrease in the
      urinary excretion from birth to puberty, and the excretion patterns fit better
      the quadratic or linear model. Fifteen amino acids showed a significant change in
      standard deviation with age. Regression-based reference limits differed
      consistently from conventional limits (<3 years) and narrower confidence
      intervals were obtained throughout the entire period studied. Avoiding
      partitioning gave rise to smoothly changing limits. Therefore, such alternative
      way of presenting amino acid reference limits may facilitate the follow-up of
      patients with inborn errors of amino acid metabolism.

PMID- 12059081
TI  - Evaluation of uncertainty of measurement in routine clinical chemistry-
      applications to determination of the substance concentration of calcium and
      glucose in serum.
AB  - We studied the uncertainty of measurement for the calcium and glucose (amount of)
      substance concentrations in serum. The evaluation follows a four-step procedure,
      which complies with the ISO document Guide to the Expression of Uncertainty in
      Measurement (GUM). The applications were chosen to represent commonly used
      measuring systems in medical laboratories. The uncertainty components are
      quantified using observations of the measuring system, and information from
      calibration certificates, instrument specifications and literature. The
      evaluation focuses on the measurement step but empirical terms are used to
      illustrate how the pre-analytical phase and patient-related issues can be
      accounted for. The software GUM Workbench was used to facilitate calculations and
      to visualize the importance of each uncertainty component. The combined standard
      uncertainties (u(c)) for the measurands were < or =2% including the pre
      analytical uncertainty sources. The patient-related source is discussed in
      relation to clinician's diagnosis and decision-making. The evaluation, as carried
      out here for calcium and glucose substance concentration measurements, can easily
      be applied to many other measurands in clinical chemistry. This work emphasizes
      that the internal quality control can provide much of the information needed in
      the uncertainty evaluation, and that external quality assessment (EQA) schemes
      are important in the control of the uncertainty evaluated by the individual
      laboratories. Due to statistical and metrological limitations routine EQA schemes
      should themselves not be used as a means of uncertainty evaluation.

PMID- 12059083
TI  - The accuracy of calculated base excess in blood.
AB  - Most equations used for calculation of the base excess (BE, mmol/l) in human
      blood are based on the fundamental equation derived by Siggaard-Andersen and
      called the Van Slyke equation: BE = Z x [[cHCO3-(P) - C7.4 HCO3-(P)] + beta x (pH
      -7.4)]. In simple approximation, where Z is a constant which depends only on
      total hemoglobin concentration (cHb, g/dl) in blood, three equations were tested:
      the ones proposed by Siggaard-Andersen (SA), the National Committee for Clinical
      Laboratory Standards (NCCLS) or Zander (ZA). They differ only slightly in the
      solubility factor for carbon dioxide (alphaCO2, mmol/l x mmHg) and in the
      apparent pK(pK'), but more significantly in the plasma bicarbonate concentration
      at reference pH (C7.4HCO3-(P), mmol/l) and in beta, the slope of the CO2-buffer
      line (mmol/l) for whole blood. Furthermore, the approximation was improved either
      by variation in Z (r(c)), or in the apparent pK (pK) with changing pH. Thus, from
      a total of seven equations and from a reference set for pH, pCO2 and BE taken
      from the literature (n=148), the base excess was calculated. Over the whole range
      of base excess (-30 to +30 mmol/l) and PCO2 (12 to 96 mmHg), mean accuracy
      (deltaBE, mmol/l) was greatest in the simple equation according to Zander and
      decreased in the following order: +/-0.86 (ZA); +/-0.94 (ZA, r(c)); +/-0.96 (SA,
      r(c)); +/-1.03 (NCCLS, r(c)); +/-1.40 (NCCLS); +/-1.48 (SA); and +/-1.50 (pK').
      For all clinical purposes, the Van Slyke equation according to Zander is the best
      choice and can be recommended in the following form: BE= (1 -0.0143 x cHb) x
      [[0.0304 x PCO2 x 10pH-6.1-24.26] + (9.5+1.63 x cHb) x (pH -7.4)] - 0.2 x cHb x
      (1-sO2), where the last term is a correction for oxygen saturation (sO2). Hence,
      base excess can be obtained with high accuracy (<1 mmol/l) from the measured
      quantities of pH, pCO2, cHb, and SO2 in any sample, irrespective of whether
      venous or arterial blood is used.

PMID- 12059082
TI  - Comparison of quick and owren prothrombin time with regard to the harmonisation
      of the International Normalised Ratio (INR) system.
AB  - Prothrombin time (PT) is tested mostly to monitor patients on oral anticoagulant
      treatment. The International Normalised Ratio (INR) was introduced to improve and
      harmonise PT results and therapeutic range globally for patient care and the
      scientific literature. We studied the Quick PT in 179 patients and the Owren PT
      in 137 patients on oral anticoagulant therapy using two different reagents for
      the two methods of measuring PT. We assessed the clinical significance of the INR
      results obtained by each method using the two reagents and compared the Quick and
      Owren methods. We conclude that with the Quick method individual INR results
      differed from each other too much clinically, while using the Owren method
      individual INR results were clinically acceptable. Our opinion is that we should
      develop the INR system using the Owren PT method rather than the Quick to improve
      patient care.

PMID- 12059084
TI  - Aspects of the development of clinical chemistry and laboratory medicine in the
      former East Germany.
AB  - Clinical chemistry and laboratory medicine developed rapidly in the
      industrialised world after the Second World War, as evidenced by the recruitment
      of physicians and natural scientists, the intensive development of methods and
      technologies, the founding of societies such as the IFCC, and the organisation of
      scientific life. In East Germany a working group of clinical pathologists and
      chemists came together in 1960, out of which grew the Gesellschaft fur Klinische
      Chemie und Laboratoriumsdiagnostik (Society for Clinical Chemistry and Laboratory
      Diagnostics) in 1968. Within the socialist health care system laboratory services
      were structured in a pyramid form based on the country's governmental districts.
      Each local diagnostic laboratory was part of a hierarchy; tests not possible in
      local laboratories were performed in larger ones. Groups of experts prescribed
      standardised methods and recommendations of quality control were administered at
      the district level. However, the funding of this quite acceptable structure was
      insufficient, resulting in difficulties. Although the development of equipment
      was carried out in close cooperation with users, it was hindered by shortages
      extant in the socialist economy. Postgraduate training of physicians, natural
      scientists, technicians and laboratory assistants was well organised, and
      clinical chemistry and pathobiochemistry were well established in the medical
      curriculum.

PMID- 12059085
TI  - University degree in clinical laboratory sciences.

PMID- 12059086
TI  - Process control reduces the laboratory turnaround time.

PMID- 12059087
TI  - Who needs two different citrate concentrations in sample tubes used for
      coagulation tests?

PMID- 12059088
TI  - Quantifying the capability of detection of measurement procedures in clinical
      laboratory sciences.

PMID- 12059089
TI  - Yet another example of lack of laboratory expertise in certain biomedical
      publications.

PMID- 12059090
TI  - Counterimmunoelectrophoresis: fast, easy and cost-effective method for the
      detection of autoantibodies to intracellular antigens.

PMID- 12059091
TI  - Waist circumference predicts insulin resistance in offspring of diabetic
      patients.
AB  - The purpose of the study was to identify a good abdominal obesity index for
      insulin resistance in offspring of diabetic patients. A total of 74 non-diabetic
      subjects (male =36; female =38) were recruited from a diabetic family study. The
      waist circumference (W), waist-hip ratio (WHR) and conicity index were used as
      the abdominal obesity indices. The body mass index (BMI) and indices obtained
      from bioelectric impedance analysis (BIA) (body fat percentage, fat mass and fat
      mass index) were used as overall obesity indices. Fasting plasma insulin (FPI),
      homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda
      Defronzo index from oral glucose tolerance test were chosen as the insulin
      sensitivity indices. We correlated obesity indices with insulin resistance
      indices with age and family adjusted. W was closely correlated in both sexes of
      subjects with Matsuda-DeFronzo index (male, r=-0.661,p<0.001; female, r=
      0.419,p=0.026), FPI (male, r=0.614,p=0.001; female, r=0.503,p=0.006) and HOMA-IR
      (male, r=0.609,p=0.001; female, r=0.472,p=0.011). WHR and its log transformation
      predicted insulin resistance only in males. BMI as an overall obesity index was
      in good correlation with Matsuda-DeFronzo index (male, r=-0.646,p<0.001; female,
      r=-0.469,p=0.012), FPI (male, r=0.711,p<0.001; female, r=0.464,p=0.013) and HOMA
      IR (male, r=0.708,p<0.001; female, r=0.469,p=0.012). Overall obesity indices from
      BIA were similar to BMI to predict insulin resistance. In conclusion, W is a good
      abdominal obesity predictor of insulin resistance in offspring of diabetic
      patients in Taiwan.

PMID- 12059092
TI  - Quality of care for persons with diabetic nephropathy: timeliness of first
      referral to nephrologist.
AB  - The aim of the present study was to assess opinions of diabetes-interested
      nephrologists in Europe as to the appropriate timing for a first referral to a
      nephrologist of a person with signs of diabetic kidney disease and to compare
      these opinions to guideline recommendations and to actual clinical findings in
      patients referred to the same nephrologists. Fifty-one nephrologists from 15
      countries responded to a questionnaire and provided information on 280 patients
      referred to them. Nearly all nephrologists favoured a first referral earlier than
      recommended by the St. Vincent Declaration guidelines, 97% of responders
      preferring a first referral at the latest at a serum creatinine of 150
      micromol/l. However, the clinical findings showed that the majority of patients
      are referred not only later than favoured by the nephrologists, but also much
      later than guideline recommendations, ca 50% of patients having entered renal
      replacement therapy within 3 months after first referral. The present results
      suggest that wide discrepancies exist between opinions on the appropriate time
      for a first referral, guideline recommendations, and actual clinical findings at
      the time of first referral. To approach the targets of the St. Vincent
      Declaration, one of which is to reduce the number of patients entering renal
      replacement therapy due to diabetic kidney disease by one third, delivery of
      diabetes care needs to be improved. Research on the actual outcomes of different
      methods for organizing delivery of care may contribute much to improving quality
      of life for people with diabetic kidney disease.

PMID- 12059093
TI  - Determination of Ca2+-atpase activity in streptozotocin-induced diabetic rat
      liver.
AB  - Microsomal Ca2+-ATPase activity was studied in control and streptozotocin (STZ)
      induced diabetic rat livers. Male rats were rendered diabetic by injection of STZ
      (45 mg/kg body weight) via the tail vein. Diabetic rats at 1, 4, 8, 10 or 15 wk
      and control rats were sacrificed. Liver tissues were obtained for the isolation
      of Ca2+-ATPase. Ca2+-ATPase activity was determined spectrophotometrically and
      lipid peroxidation [measured as tiobarbituric acid reactive substances (TBARS)]
      in liver tissues was determined spectrofluorometrically. Total calcium was
      measured by atomic absorption spectrophotometry. Blood glucose levels of the
      diabetic animals were >500 mg/dl at 4, 8, 10 and 15 wk of diabetes. Ca2+-ATPase
      activity was significantly decreased at all weeks of diabetes compared to control
      group (p<0.001). Ca2+-ATPase activity of control rats was 0.193 +/- 0.015 U/I
      whereas activity was 0.130 +/- 0.015 U/I at 15 wk of diabetes. The difference in
      calcium levels of diabetic rat livers was not significantly different compared to
      control group. On the other hand TBARS were elevated by 67% at 15 wk of diabetes.
      The decrease in enzyme activity may have been caused by elevated TBARS levels
      observed in liver tissue sindicative of increased lipid peroxidation.

PMID- 12059094
TI  - Management of cardiovascular risk in diabetic patients: evolution or revolution?
AB  - Diabetes is associated with a marked increase in the risk of cardiovascular
      disease. Epidemiological evidence shows that hyperglycemia, hypertension and
      disorders of both lipid and thrombosis are involved in the etiology of
      cardiovascular disease in diabetes. Intervention trials on each of such factors
      have demonstrated a favourable effect in terms of reduction of cardiovascular
      disease, suggesting that even in diabetic patients in whom blood glucose levels
      are adequately controlled, other cardiovascular risk factors, such as
      hyperlipidemia, hypertension and prothrombotic state, should be aggressively
      treated. The need for an aggressive treatment has been recently underscored by
      the UKPDS (United Kingdom Prospective Diabetes Study) researchers who suggest
      that "polypharmacy" is now needed for the prevention of diabetic complications,
      implying that this approach requires an adequate control of all cardiovascular
      risk factors even using associations of drugs for each of them. A thorough
      application of these concepts might appear difficult in particular when the
      resource cost is considered. However, it has been shown that blood glucose, blood
      pressure and serum lipid control are advantageous in diabetic patients not only
      in terms of cost/benefit ratio but also in terms of quality of life. In the
      present article, we will briefly review this evidence and discuss the ethical and
      socioeconomic concerns that may subsequently rise.

PMID- 12059095
TI  - Is type 2 diabetes a chronic inflammatory/autoimmune disease?
AB  - The classification of diabetes mellitus into 2 main types, defined as Type 1 and
      2 diabetes (T1DM, T2DM) relies mostly on the requirement of insulin therapy and
      on the presence of detectable immunologic abnormalities. However, this
      distinction is far from straightforward and there is considerable overlap between
      these 2 types of diabetes. Islet cell autoimmunity, which is characteristic of
      T1DM, appears in fact to be present in up to 10-15% of subjects diagnosed
      clinically with T2DM. In the UK Prospective Diabetes Study (UKPDS), it was
      reported that in patients diagnosed with in T2DM, the presence of autoantibodies
      to the enzyme glutamic acid decarboxylase (GAD) and cytoplasmic islet cell
      antibodies (ICA) were a predictor of insulin requirement as compared with
      patients not carrying these autoantibodies. These results are strikingly similar
      to a number of prospective studies carried out in childhood diabetes. If islet
      cell autoimmunity is truly present in 10-15% of subjects clinically diagnosed
      with T2DM, up to two million Americans might have an unidentified autoimmune form
      of T2DM, a prevalence similar to that of recent onset childhood diabetes. In
      addition, we found that in a subset of T2DM patients, a pronounced activation of
      the acute phase response that seems to be associated with islet cell
      autoimmunity. These results may in part explain the defect in insulin secretion
      as well as insulin resistance seen in T2DM. The identification of a subgroup of
      individuals at risk of developing T2DM using autoantibody as well as inflammatory
      markers is of public health interest, not only for the correct classification of
      diabetes, but also because immunomodulatory therapeutic strategies could
      potentially be instituted sufficiently early in a large number of patients
      diagnosed as having T2DM and most likely delay the onset of insulin requirement
      and the complications related with hyperglycemia.

PMID- 12059096
TI  - Impaired glucose tolerance is not associated with lipid intolerance.
AB  - Post-prandial (pp) hypertriglyceridaemia (HTG) has an important role in the
      development of atherosclerosis in Type 2 diabetes. Impaired glucose tolerance
      (IGT) is associated with an increased risk of atherosclerosis and increased level
      of fasting triglycerides (TG). The aim of this study was to analyse pp HTG and
      the composition of TG-rich lipoproteins in carefully selected subjects with IGT
      in comparison to controls with normal glucose tolerance (NGT). Fifteen men with
      IGT and 27 men with NGT, aged 44 to 70 yr, were examined. All study participants
      were non-smokers and had fasting TG <4.6 mmol/l. The subjects underwent an oral
      glucose tolerance test (75 g glucose) and a lipid-glucose tolerance test (LGTT;
      92 g fat, 126 g carbohydrate), that allowed the assessment of lipid and glucose
      tolerance in one test. HbA1C, plasma glucose and lipids were measured by routine
      methods. Lipoprotein subfraction analysis of VLDL (VLDL1: Sf60-400 and VLDL2:
      Sf20-60) was conducted in a fasting state, as well as 4 hr after the LGTT using a
      density gradient ultracentrifugation with a subsequent compositional analysis. No
      significant difference was found either for fasting or pp TG, or for area under
      curve (AUC) -TG (12.21 +/- 4.27 mmol/l x 6 hr vs 13.95 +/- 6.74 mmol/l x 6 hr;
      p>0.05) between the IGT and NGT. A highly significant correlation was found
      between the fasting TG and the AUC-TG (r=0.925; p<0.01). To avoid bias by
      differences in fasting plasma TG known to affect lipid tolerance we investigated
      11 matched pairs for fasting TG. Also, the matched-pairs evaluation pp TG course
      did not differ significantly from the IGT and NGT. No significant difference for
      fasting or pp levels of VLDL1 and VLDL2, or for the TG content of chylomicron,
      VLDL1 and VLDL2 and for the percentage of TG in VLDL1 and VLDL2 was found between
      the IGT and NGT group. In conclusion, IGT subjects with a similar level of
      fasting TG do not exhibit lipid intolerance. Our data suggest that glucose
      intolerance should precede lipid intolerance.

PMID- 12059097
TI  - Seroprevalence of Helicobacter pylori in children with type 1 diabetes mellitus
      in Sardinia.
AB  - A few studies have reported an increased prevalence of Helicobacterpylori (HP)
      infection in diabetic subjects, which may be one of the causes of
      gastrointestinal symptoms and chronic atrophic gastritis frequently seen in
      diabetes of long duration. We determined the prevalence of HP infection in
      children and adolescents with Type 1 diabetes mellitus (T1DM) in the area of
      Sassari (northern Sardinia, Italy), which is characterized by an ethnically
      homogenous population at high risk of T1DM. HP IgG and IgA titres were measured
      in 138 patients with T1DM and 138 age-matched healthy controls. The percentage of
      infected subjects did not differ between T1DM patients (29.7%) and controls
      (32.6%). Globally, infected subjects were more than 1 yr older (13.0 +/- 2.7 yr)
      than non-infected ones (11.8 +/- 2.9 yr), independently of the presence of T1DM;
      in most HP-positive subjects infection was asymptomatic, and only 2 subjects in
      each group reported clinically relevant symptoms. HP-positive and HP-negative
      diabetic patients had the same duration of the disease (5.6 +/- 3.5 vs 5.5 +/-
      3.6 yr) and received very similar doses of insulin (0.94 +/- 0.27 vs 0.96 +/- 0.4
      IU/kg/d), whereas mean HbA1c was significantly lower in HP-positive patients (7.8
      +/- 1.6% vs 8.6 +/- 1.7%,p=0.02). We conclude that the prevalence of HP infection
      is not higher in Sardinian children with T1DM as compared to controls of similar
      age, and the overall clinical impact of HP infection in terms of gastrointestinal
      symptoms and diabetic control seems to be low.

PMID- 12059098
TI  - Lispro insulin treatment in comparison with regular human insulin in type 2
      diabetic patients living in nursing homes.
AB  - Lispro insulin has been demonstrated to be effective in reducing post-prandial
      blood glucose levels. Thirty Type 2 diabetic subjects (18 women and 12 men)
      living in nursing homes, aged 77 +/- 3 yr, mean systolic pressure 147 +/- 6 and
      diastolic 82 +/- 4 mmHg, body mass index 27.5 +/- 2 kg/m2, known diabetes
      duration 10.1+/- 0.7 yr, mean HbA1c 8.5 +/- 0.8%, fasting C-peptide 1.3 +/- 0.5
      ng/ml, treated with intensive (4 insulin injections per day) therapy, mean
      insulin need 45 +/- 7 IU per day, with 2.0 +/- 0.6 hypoglycaemic (blood glucose
      level below 60 mg/dl) and 13 +/- 4 hyperglycaemic episodes (blood glucose level
      over 250 mg/dl) per wk, were studied. Their own informed consent or that provided
      by a family member was obtained before these patients took part in a therapy
      protocol divided into 3 four-mo periods; in the 1st and 3rd period regular
      insulin (75% of the total dose) was administered 30 min before each meal, in the
      second lispro insulin was administered immediately at the end of each meal,
      according to the carbohydrate quantity ingested with the meal. During the lispro
      treatment period there was a significant decrease of the mean daily blood glucose
      166 +/- 12 regular vs 143 +/- 9 lispro; p<0.01, HbA1c 8.5 +/- 0.6 regular vs 7.6
      +/- 0.5 % lispro; p<0.01, triglycerides 261 +/- 40 regular vs 218 +/- 20 mg/dl
      lispro; p<0.01, hypoglycaemic 2.1 +/- 0.2 regular vs 1.6 +/- 0.3 lispro; p<0.01
      and hyperglicaemic 12 +/- 1 regular vs 8 +/- 0.3 lispro; p<0.01 episodes per wk.
      No statistical difference was recorded between the 1st and the 3rd treatment
      period. The lispro treatment produced a better metabolic control (mean blood
      glucose, HbA1c, triglycerides), better lifestyle (less hypo- and hyperglycaemic
      episodes), better nurse management (no waiting time before, but a more accurate
      calculation of the right dose administered immediately at the end of each meal).
      Lispro insulin seems to be a good therapeutic choice not only in Type 1, but also
      in the large population of elderly Type 2 diabetic patients.

PMID- 12059099
TI  - Enhanced resistance to seed-transmitted bacterial diseases in transgenic rice
      plants overproducing an oat cell-wall-bound thionin.
AB  - Bacterial attack is a serious agricultural problem for growth of rice seedlings
      in the nursery and field. The thionins purified from seed and etiolated seedlings
      of barley are known to have antimicrobial activity against necrotrophic
      pathogens; however, we found that no endogenous rice thionin genes alone are
      enough for resistance to two major seed-transmitted phytopathogenic bacteria,
      Burkholderia plantarii and B. glumae, although rice thionin genes constitutively
      expressed in coleoptile, the target organ of the bacteria. Thus, we isolated
      thionin genes from oat, one of which was overexpressed in rice. When wild-type
      rice seed were germinated with these bacteria, all seedlings were wilted with
      severe blight. In the seedling infected with B. plantarii, bacterial staining was
      intensively marked around stomata and intercellular spaces. However, transgenic
      rice seedlings accumulating a high level of oat thionin in cell walls grew almost
      normally with bacterial staining only on the surface of stomata. These results
      indicate that the oat thionin effectively works in rice plants against bacterial
      attack.

PMID- 12059100
TI  - Nod factor induction of reactive oxygen species production is correlated with
      expression of the early nodulin gene rip1 in Medicago truncatula.
AB  - Plant genes that are specifically activated by the rhizobial
      lipochitooligosaccharide signal molecule (Nod factor) in legume hosts are
      collectively referred to as nodulins. Although nodulin gene expression is both
      spatially and temporally correlated with symbiosis, the function of these genes
      and the molecular events underlying their expression remain unknown. Sequence
      analysis of rip1, an early nodulin gene encoding a putative peroxidase protein,
      revealed the existence of sequence motifs with homology to reactive oxygen
      species (ROS) responsive cis elements. Here we report that recognition of
      compatible Nod factor rapidly stimulates a spatially localized production of
      reactive oxygen species in legume roots. Sinorhizobium meliloti mutants that
      produce an altered Nod factor structure and a nonnodulating plant mutant, dmi1-1,
      that is implicated in Nod factor signal transduction are equally impaired in the
      ability to elicit ROS production and rip1 expression. Interestingly, both rip1
      transcription and ROS production exhibit the same tissue-specific pattern of
      localization. Moreover, exogenous hydrogen peroxide is sufficient to activate
      rip1 transcription. Taken together, these results suggest that ROS production is
      a consequence of specific Nod factor perception and implicate H2O2 produced
      during this response as a mediator of Nod factor-induced rip1 expression.

PMID- 12059101
TI  - Phylogeny and genomic organization of the TIR and non-tIR NBS-LRR resistance gene
      family in Medicago truncatula.
AB  - Sequences homologous to the nucleotide binding site (NBS) domain of NBS-leucine
      rich repeat (LRR) resistance genes were retrieved from the model legume M.
      truncatula through several methods. Phylogenetic analysis classified these
      sequences into TIR (toll and interleukin-1 receptor) and non-TIR NBS subfamilies
      and further subclassified them into several well-defined clades within each
      subfamily. Comparison of M. truncatula NBS sequences with those from several
      closely related legumes, including members of the tribes Trifoleae, Viceae, and
      Phaseoleae, reveals that most clades contain sequences from multiple legume
      species. Moreover, sequences from species within the closely related Trifoleae
      and Viceae tribes (e.g., Medicago and Pisum spp.) tended to be cophyletic and
      distinct from sequences of Phaseoleae species (e.g., soybean and bean). These
      results suggest that the origin of major clades within the NBS-LRR family predate
      radiation of these Papilionoid legumes, while continued diversification of these
      sequences mirrors speciation within this legume subfamily. Detailed genetic and
      physical mapping of both TIR and non-TIR NBS sequences in M. truncatula reveals
      that most NBS sequences are organized into clusters, and few, if any, clusters
      contain both TIR and non-TIR sequences. Examples were found, however, of physical
      clusters that contain sequences from distinct phylogenetic clades within the TIR
      or non-TIR subfamilies. Comparative mapping reveals several blocks of resistance
      gene loci that are syntenic between M. truncatula and soybean and between M.
      truncatula and pea.

PMID- 12059102
TI  - PPI1: a novel pathogen-induced basic region-leucine zipper (bZIP) transcription
      factor from pepper.
AB  - We have isolated a full-length cDNA, PPI1 (pepper-PMMV interaction 1), encoding a
      novel basic region-leucine zipper (bZIP) DNA-binding protein, from expressed
      sequence tags differentially expressed in Capsicum chinense P1257284 infected
      with Pepper mild mottle virus (PMMV). PPI1 encodes a predicted protein of 170
      amino acids and contains a putative DNA-binding domain that shares significant
      amino acid identity with ACGT-binding domains of members of the bZIP DNA-binding
      protein family. PPI1 was localized in the nucleus and had transcriptional
      activation activity in yeast. Transcripts of the PPI1 gene were preferentially
      induced during an incompatible interaction by inoculation with PMMV, Pseudomonas
      syringae pv. syringae 61, and Xanthomonas campestris pv. vesicatoria race 3.
      However, the PPII gene was not induced by abiotic stressors that activate the
      plant defense-signaling pathway. Our data provide the first evidence that a bZIP
      transcription factor is preferentially induced by pathogen attack, suggesting
      that PPI1 may play a specific functional role in the regulation of expression of
      plant defense-related genes.

PMID- 12059103
TI  - Cloning and characterization of an esophageal-gland-specific pectate lyase from
      the root-knot nematode Meloidogyne javanica.
AB  - Root-knot nematodes (Meloidogynejavanica) are obligate sedentary endoparasites
      that must penetrate the host root to initiate their life cycle. Many enzymes are
      secreted by the nematode to facilitate host penetration; required enzymes may
      include pectate lyases and cellulases. Using differential screening, a class III
      pectate lyase, Mj-pel-1 (M. javanica pectate lyase 1), was cloned from a library
      enriched for esophageal gland genes. DNA gel blotting confirmed that the Mj-pel-1
      gene was of nematode origin and a member of a small multigene family. In situ
      hybridization localized the expression of Mj-pel-1 to the basal cells of the
      esophageal glands, while immunolocalization detected the protein in the
      esophageal glands as well as on the exterior of the nematode, confirming that the
      protein is secreted. When MJ-PEL-1 was expressed in Pichia pastoris, the
      resulting protein was active. The pH optimum of MJ-PEL-1 was 10.0, and the enzyme
      was five times more active on pectate than on pectin. Like other class III
      pectate lyases, MJ-PEL-1 also displayed an absolute requirement for Ca2+. The
      root-knot nematode migrates through the middle lamella of the plant root;
      therefore, MJ-PEL-1 may be an important enzyme early in the infection process.

PMID- 12059104
TI  - Characterization of a novel, defense-related Arabidopsis mutant, cir1, isolated
      by luciferase imaging.
AB  - In order to identify components of the defense signaling network engaged
      following attempted pathogen invasion, we generated a novel PR-1::luciferase
      (LUC) transgenic line that was deployed in an imaging-based screen to uncover
      defense-related mutants. The recessive mutant designated cir1 exhibited
      constitutive expression of salicylic acid (SA), jasmonic acid (JA)/ethylene, and
      reactive oxygen intermediate-dependent genes. Moreover, this mutation conferred
      resistance against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000
      and a virulent oomycete pathogen Peronospora parasitica Noco2. Epistasis analyses
      were undertaken between cir1 and mutants that disrupt the SA (nprl, nahG), JA
      (jar1), and ethylene (ET) (ein2) signaling pathways. While resistance against
      both P. syringae pv. tomato DC3000 and Peronospora parasitica Noco2 was partially
      reduced by npr1, resistance against both of these pathogens was lost in an nahG
      genetic background. Hence, cirl-mediated resistance is established via NPR1
      dependent and -independent signaling pathways and SA accumulation is essential
      for the function of both pathways. While jar1 and ein2 reduced resistance against
      P. syringae pv. tomato DC3000, these mutations appeared not to impact cir1
      mediated resistance against Peronospora parasitica Noco2. Thus, JA and ET
      sensitivity are required for cir1-mediated resistance against P. syringae pv.
      tomato DC3000 but not Peronospora parasitica Noco2. Therefore, the cir1 mutation
      may define a negative regulator of disease resistance that operates upstream of
      SA, JA, and ET accumulation.

PMID- 12059105
TI  - Deleterious impact of a virulent bacteriophage on survival and biocontrol
      activity of Pseudomonas fluorescens strain CHAO in natural soil.
AB  - Many biotic and abiotic factors affect the persistence and activity of beneficial
      pseudomonads introduced into soil to suppress plant diseases. One such factor may
      be the presence of virulent bacteriophages that decimate the population of the
      introduced bacteria, thereby reducing their beneficial effect. We have isolated a
      lytic bacteriophage (phi)GP100) that specifically infects the biocontrol
      bacterium Pseudomonas fluorescens CHA0 and some closely related Pseudomonas
      strains. phiGP100 was found to be a double-stranded-DNA phage with an icosahedral
      head, a stubby tail, and a genome size of approximately 50 kb. Replication of
      phiGP100 was negatively affected at temperatures higher than 25 degrees C.
      phiGP100 had a negative impact on the population size and the biocontrol activity
      of P. fluorescens strain CHA0-Rif (a rifampicin-resistant variant of CHA0) in
      natural soil microcosms. In the presence of phiGP100, the population size of
      strain CHA0-Rif in soil and on cucumber roots was reduced more than 100-fold. As
      a consequence, the bacterium's capacity to protect cucumber against a root
      disease caused by the pathogenic oomycete Pythium ultimum was entirely abolished.
      In contrast, the phage affected neither root colonization and nor the disease
      suppressive effect of a phiDGP100-resistant variant of strain CHA0-Rif. To our
      knowledge, this study is the first to illustrate the potential of phages to
      impair biocontrol performance of beneficial bacteria released into the natural
      soil environment.

PMID- 12059106
TI  - Identification and characterization of a soybean ethylene-responsive element
      binding protein gene whose mRNA expression changes during soybean cyst nematode
      infection.
AB  - Ethylene-responsive element-binding proteins (EREBPs) are members of a family of
      plant transcription factors. Conserved EREBP domains of these proteins bind to
      the GCC box, an ethylene-responsive promoter element found in many pathogenesis
      related (PR) genes. Using degenerate primers to the EREBP domain from diverse
      plant species, an EREBP homolog was isolated from a soybean cDNA library. Gel
      mobility-shift assays revealed that the translation product of this cDNA bound
      specifically to GCC box sequences. We, therefore, named this gene Glycine max
      ethylene-responsive element-binding protein 1 (GmEREBP1), i.e., a gene coding for
      the first confirmed GCC box-binding protein of soybean. GmEREBP1 mRNA abundance
      was analyzed by RNA blot hybridizations in soybean roots and shoots of cultivars
      Corsoy 79 and Hartwig, which are susceptible and resistant, respectively, to the
      soybean cyst nematode (Heterodera glycines). These analyses revealed that
      GmEREBP1 is expressed in a root-preferential manner and that GmEREBP1 mRNA
      abundance is changed after H. glycines infection. GmEREBP1 mRNA abundance
      decreased in infected (susceptible) 'Corsoy 79' roots, whereas it increased in
      abundance in infected (resistant) 'Hartwig' roots. Furthermore, ethephon
      treatment repressed GmEREBP1 mRNA accumulation in both cultivars, whereas
      wounding increased expression in both cultivars. These changes in mRNA steady
      state levels suggest that GmEREBP1 plays a role in soybean-H. glycines
      interactions.

PMID- 12059107
TI  - Plant defense genes associated with quantitative resistance to potato late blight
      in Solanum phureja x dihaploid S. tuberosum hybrids.
AB  - Markers corresponding to 27 plant defense genes were tested for linkage
      disequilibrium with quantitative resistance to late blight in a diploid potato
      population that had been used for mapping quantitative trait loci (QTLs) for late
      blight resistance. Markers were detected by using (i) hybridization probes for
      plant defense genes, (ii) primer pairs amplifying conserved domains of resistance
      (R) genes, (iii) primers for defense genes and genes encoding transcriptional
      regulatory factors, and (iv) primers allowing amplification of sequences flanking
      plant defense genes by the ligation-mediated polymerase chain reaction. Markers
      were initially screened by using the most resistant and susceptible individuals
      of the population, and those markers showing different allele frequencies between
      the two groups were mapped. Among the 308 segregating bands detected, 24 loci
      (8%) corresponding to six defense gene families were associated with resistance
      at chi2 > or = 13, the threshold established using the permutation test at P =
      0.05. Loci corresponding to genes related to the phenylpropanoid pathway
      (phenylalanine ammonium lyase [PAL], chalcone isomerase [CHI], and chalcone
      synthase [CHS]), loci related to WRKY regulatory genes, and other -defense genes
      (osmotin and a Phytophthora infestans-induced cytochrome P450) were significantly
      associated with quantitative disease resistance. A subset of markers was tested
      on the mapping population of 94 individuals. Ten defense-related markers were
      clustered at a QTL on chromosome III, and three defense-related markers were
      located at a broad QTL on chromosome XII. The association of candidate genes with
      QTLs is a step toward understanding the molecular basis of quantitative
      resistance to an important plant disease.

PMID- 12059108
TI  - The fixM flavoprotein modulates inhibition by AICAR or 5'AMP of respiratory and
      nitrogen fixation gene expression in Sinorhizobium meliloti.
AB  - AICAR, a purine-related metabolite, was recently shown to inhibit respiratory and
      nifA gene expression in Sino-rhizobium meliloti. Here, we demonstrate that AICAR
      has essentially no or little effect in a wild-type S. meliloti strain and
      inhibits respiratory and nitrogen fixation gene expression only in specific
      mutant backgrounds. We have analyzed in detail a mutant in which addition of
      AICAR inhibited fixK,fixN,fixT and nifA expression. The corresponding gene,fixM,
      is located just downstream of fixK1 on pSymA megaplasmid and encodes a
      flavoprotein oxidoreductase. 5'AMP, a structural analogue of AICAR, mimicked
      AICAR effect as well as the nucleoside precursors AICAriboside and adenosine. The
      mode of action of AICAR and 5'AMP in vivo was investigated. We demonstrate that
      AICAR does not affect FixK transcriptional activity and instead regulates fixK
      and nifA gene expression. We hypothesize that AICAR and 5'AMP may modulate,
      possibly indirectly, the activity of the FixLJ two-component regulatory system.
      The possible physiological roles of AICAR, 5'AMP, and fixM in the context of
      symbiosis are discussed.

PMID- 12059109
TI  - NHL25 and NHL3, two NDR1/HIN1-1ike genes in Arabidopsis thaliana with potential
      role(s) in plant defense.
AB  - The Arabidopsis genome contains 28 genes with sequence homology to the
      Arabidopsis NDR1 gene and the tobacco HIN1 gene. Expression analysis of eight of
      these genes identified two (NHL25 and NHL3 for NDR1/HIN1-like) that show pathogen
      dependent mRNA accumulation. Transcripts did not accumulate during infection with
      virulent Pseudomonas syringae pv. tomato DC3000 but did accumulate specifically
      when the bacteria carried any of the four avirulence genes avrRpm1, avrRpt2,
      avrB, or avrRps4. Furthermore, expression of avrRpt2 in plants containing the
      corresponding resistance gene, RPS2, was sufficient to induce transcript
      accumulation. However, during infection with an avirulent oomycete, Peronospora
      parasitica isolate Cala-2, only NHL25 expression was reproducibly induced.
      Salicylic acid (SA) treatment can induce expression of NHL25 and NHL3. Studies
      performed on nahG plants showed that, during interaction with avirulent bacteria,
      only the expression of NHL25 but not that of NHL3 was affected. This suggests
      involvement of separate SA-dependent and SA-independent pathways, respectively,
      in the transcriptional activation of these genes. Bacteria-induced gene
      expression was not abolished in ethylene- (etrl-3 and ein2-1) and jasmonate-
      (coil-1) insensitive mutants or in mutants impaired in disease resistance (ndr1-1
      and pad4-1). Interestingly, NHL3 transcripts accumulated after infiltration with
      the avirulent hrcC mutant of Pseudomonas syringae pv. tomato DC3000 and nonhost
      bacteria but not with the virulent Pseudomonas syringae pv. tomato DC3000,
      suggesting that virulent bacteria may suppress NHL3 expression during
      pathogenesis. Hence, the expression patterns and sequence homology to NDR1 and
      HIN1 suggest one or more potential roles for these genes in plant resistance.

PMID- 12059110
TI  - Intratumoral low-volume jet-injection for efficient nonviral gene transfer.
AB  - Jet-injection has become an applicable technology among other established
      nonviral delivery systems, such as particle bombardment or in vivo
      electroporation. The low-volume jet injector employed in this study uses
      compressed air to inject solutions of 1.5-10 microL containing naked DNA into the
      desired tissue. The novel design of this prototype makes multiple jet-injections
      possible. Therefore, repeated jet-injections into one target tissue can be
      performed easily. This jet-injector hand-held system was used for the direct in
      vivo gene transfer of plasmid DNA into tumors to achieve efficient expression of
      reporter genes (beta-galactosidase, green fluorescent protein [GFP]) and of
      therapeutic genes (TNF-alpha) in different tumor models. The study presented here
      revealed the key parameters of efficient in vivo jet-injection (jet-injection
      volume, pressure, jet penetration, DNA stability) to define the optimal
      conditions for a jet-injection-aided nonviral gene therapy.

PMID- 12059111
TI  - Typing dinucleotide repeats under nondenaturing conditions with single-base
      resolution and high sizing precision.
AB  - Dinucleotide repeats are genetic markers that are useful for many purposes,
      including genetic epidemiology, population genetics, and genetic diagnostics. The
      accuracy of analyses based on dinucleotide repeat polymorphisms is highly
      dependent on the success achieved in minimizing genotyping errors. Genotyping
      errors in dinucleotide repeat typing may arise for various reasons, including
      polymerase chain reaction (PCR) processing errors and the use of unsuitable
      electrophoretic conditions for resolving amplification products (i.e., lack of
      single-base resolution and inadequate precision in allele sizing). We have
      recently described a nondenaturing electrophoretic system useful for detecting
      PCR processing errors that lead to misidentification of heterozygotes as
      homozygotes in (AC)n repeat typing. Here, we show that this system also allows
      resolution of (AC)n repeats in native conditions with single-base resolution and
      high sizing precision, on the basis of an analysis of seven human (AC)n repeats
      ranging in size from 72 to 217 bp. This PAGE system is thus also useful for
      reducing the likelihood both of allele misidentification due to the absence of
      single-base resolution and of inaccuracies in allele sizing due to anomalous
      electrophoretic migrations among the alleles within an (AC)n repeat.

PMID- 12059112
TI  - Modification of fatty acid composition in tomato (Lycopersicon esculentum) by
      expression of a borage delta6-desaturase.
AB  - The improvement of nutritional quality is one potential application for the
      genetic modification of plants. One possible target for such manipulation is the
      modification of fatty acid metabolism. In this work, expression of a borage
      delta6-desaturase cDNA in tomato (Lycopersicon esculentum L.) has been shown to
      produce gamma-linolenic acid (GLA; 18:83 delta6,9,12) and octadecatetraenoic acid
      (OTA; 18:4 delta6,9,12,15) in transgenic leaf and fruit tissue. This genetic
      modification has also, unexpectedly, resulted in a reduction in the percentage of
      linoleic acid (LA 18:2 delta9,12) and a concomitant increase in the percentage of
      alpha-linolenic acid (ALA; 18:3 delta9,12,15) in fruit tissue. These changes in
      fatty acid composition are thought to be beneficial for human health.

PMID- 12059114
TI  - Approaches to the analysis of gene expression using mRNA: a technical overview.
AB  - Messenger RNA is the blueprint for all proteins expressed within living systems.
      Therefore, the study of mRNA expression within normal and diseased tissues is
      central to our understanding of biological systems. However, blueprints, in
      themselves, perform no function unless they are used to produce the material for
      which they code. Spurious results may frequently result from poorly designed or
      inappropriate studies. This review seeks to highlight both the pitfalls and the
      promise of various approaches to the analysis of mRNA in different systems and to
      place these studies in the wider context of research approaches aimed at
      understanding the function of living systems. The various techniques for the
      analysis of mRNA are discussed, with particular reference to their potential uses
      and problems and relevant examples are cited from the literature. It is hoped
      that this overview of the uses of analytical approaches will allow both the
      novice researcher and the more experienced scientist to better structure research
      approaches.

PMID- 12059115
TI  - Cancer immunotherapy with interleukin-2-activated natural killer cells.
AB  - Natural killer (NK) cells are a subset of lymphocytes with a distinct morphologic
      appearance (large granular lymphocytes [LGL]) and the ability to kill virally
      infected and tumor targets but to spare most normal cells. NK cells respond to a
      variety of biologic agents, such as interleukin-2 (IL-2), or interferons, by
      upregulation of cytolytic, secretory, and proliferative functions. In cancer
      bearing hosts, NK cells have been considered to be the major component of
      antitumor immunity responsible for rapid elimination of malignant cells from the
      blood. More recently, however, studies have demonstrated the ability of
      adoptively transferred, IL-2-activated NK cells to selectively localize into
      solid tumors tissue and to eliminate established tumors. While these findings
      indicate a role for NK cells in cancer immunotherapy, additional studies are
      needed in both animal models and in humans to optimize clinical protocols of
      cancer therapy based on these cells.

PMID- 12059113
TI  - The development and use of vaccine adjuvants.
AB  - Interest in vaccine adjuvants is intense and growing, because many of the new
      subunit vaccine candidates lack sufficient immunogenicity to be clinically
      useful. In this review, I have emphasized modern vaccine adjuvants injected
      parenterally, or administered orally, intranasally, or transcutaneously with
      licensed or experimental vaccines in humans. Every adjuvant has a complex and
      often multi-factorial immunological mechanism, usually poorly understood in vivo.
      Many determinants of adjuvanticity exist, and each adjuvanted vaccine is unique.
      Adjuvant safety is critical and can enhance, retard, or stop development of an
      adjuvanted vaccine. The choice of an adjuvant often depends upon expensive
      experimental trial and error, upon cost, and upon commercial availability.
      Extensive regulatory and administrative support is required to conduct clinical
      trials of adjuvanted vaccines. Finally, comparative adjuvant trials where one
      antigen is formulated with different adjuvants and administered by a common
      protocol to animals and humans can accelerate vaccine development.

PMID- 12059116
TI  - Adrenergic receptor genes: cDNA and genomic library construction.
AB  - Adrenergic receptors mediate the central and peripheral actions of norepinephrine
      and epinephrine and are pharmacologically divided into three major types, alpha
      1, alpha-2, and beta. These types are further subdivided into alpha-1A, alpha-1B,
      and alpha-1D; alpha-2A, alpha-2B, and alpha-2C; and beta-1, beta-2, and beta-3,
      respectively. Adrenergic receptor sequence information is presented in three
      tables with respect to species, subtype identification, GenBank accession number,
      source of the nucleic acid sequence, the presence of a 5' flanking region
      upstream of the transcription start site, and the nucleotides defined as introns,
      coding regions, or 3' and/or 5' untranslated but transcribed (UTR) regions.
      Sequences have been assigned to adrenergic subtype categories based on sequence
      comparison using either FASTA or denogram of Pileup from the GCG sequence
      analysis program rather than as described in the author definition line. Sequence
      information found in these tables can be important for probe development for
      screening libraries for isolating adrenergic receptor genes from species other
      than the most common species. Where commercial libraries for specific tissue or
      species needs are not available, we have described construction of genomic cosmid
      libraries or PCR-based synthesis of a cDNA library using a microgram of RNA.

PMID- 12059117
TI  - Luc Montagnier--discoverer of the AIDS virus.

PMID- 12059118
TI  - Cerebrospinal fluid dynamics and shunt responsiveness in patients with normal
      pressure hydrocephalus.

PMID- 12059119
TI  - Use of cerebrospinal fluid flow rates measured by phase-contrast MR to predict
      outcome of ventriculoperitoneal shunting for idiopathic normal-pressure
      hydrocephalus.
AB  - OBJECTIVE: To determine whether favorable clinical response and magnitude of
      improvement are associated with increased aqueductal cerebrospinal fluid (CSF)
      flow rates in patients who undergo ventriculoperitoneal shunting (VPS) for
      idiopathic normal-pressure hydrocephalus (NPH). PATIENTS AND METHODS: Between
      January 1995 and June 2000, 49 patients (14 men and 35 women; mean age, 72.9
      years; range, 54-88 years) underwent magnetic resonance quantification of
      aqueductal CSF flow followed by VPS for presumed idiopathic NPH at the Mayo
      Clinic, Rochester, Minn. Logistic regression models for the odds of any
      improvement in score as a function of aqueductal CSF flow and separate models for
      any improvement in gait, incontinence, cognition, and total score were
      constructed. RESULTS: Forty-two patients (86%) had improvement in gait at
      postoperative follow-up (mean, 10 months). Of the 32 patients with incontinence,
      27 (69%) improved. Of the 36 patients with cognitive impairment, 16 (44%)
      improved. In univariate and fully adjusted models, increased CSF flow through the
      aqueduct was not significantly associated with improvement or the magnitude of
      improvement in gait, cognition, or incontinence. Thirty-six patients underwent
      high-volume lumbar puncture preoperatively, of whom 5 (14%) had no response. The
      aqueductal CSF flow rates of these 5 patients were significantly higher than
      those of the patients who improved after lumbar puncture. Postoperative
      complications occurred in 15 patients. The aqueductal CSF flow rates in these 15
      patients were not significantly different from those of patients who experienced
      no complications. CONCLUSION: Among patients who underwent VPS for the treatment
      of NPH, measurement of CSF flow through the cerebral aqueduct did not reliably
      predict which patients would improve after shunting or the magnitude of
      improvement.

PMID- 12059120
TI  - Use of a simple clinical score to predict prognosis of patients with normal or
      mildly abnormal resting electrocardiographic findings undergoing evaluation for
      coronary artery disease.
AB  - OBJECTIVE: To determine whether a simple clinical score, which was shown
      previously to predict the likelihood of severe coronary artery disease (CAD) in
      patients referred for coronary angiography, could predict prognosis in a separate
      cohort of patients with normal or mildly abnormal findings on their resting
      electrocardiogram (ECG) who were undergoing noninvasive evaluation for possible
      CAD. PATIENTS AND METHODS: The study group included 2255 symptomatic patients
      with normal (n=1466) or mildly abnormal (nonspecific ST-T-wave abnormalities;
      n=789) findings on their resting ECG who were referred for exercise thallium
      testing between 1989 and 1991. Follow-up was 94% complete at a mean +/- SD
      duration of 6.9+/-1.5 years. The clinical score, which ranged from 0 (lowest
      risk) to 10 (highest risk), was calculated by awarding 1 point each for male sex,
      history of myocardial infarction, typical angina, diabetes mellitus, insulin use,
      and each decade of age older than 40 years. RESULTS: In each ECG group, the
      clinical score was a significant predictor of cardiac death, nonfatal myocardial
      infarction, or late revascularization, considered individually or combined,
      unadjusted or with adjustment for age. Most patients had a score lower than 5;
      these patients had an excellent 5-year cardiac survival rate (99.7% for the
      normal ECG findings group and 98.8% for the ST-T-wave abnormalities group). The
      small subset of patients with a score higher than 5 had a much lower 5-year
      survival rate (923% for the 8% of patients with normal ECG findings and 86.6% for
      the 14% of patients with ST-T-wave abnormalities). For patients with a score of
      5, the 5-year survival rate was 97.7% for the normal ECG findings group and 95.9%
      for the ST-T-wave abnormalities group. CONCLUSION: In symptomatic patients with
      known or suspected CAD and normal or mildly abnormal resting ECG findings, this
      simple, easily computed clinical score is a useful and valid tool to help
      determine prognosis.

PMID- 12059121
TI  - Prevalence of hemochromatosis-related symptoms among individuals with mutations
      in the HFE gene.
AB  - OBJECTIVE: To determine the prevalence of hemochromatosis-related symptoms in
      homozygotes for the HFE mutation C282Y compared with controls without HFE
      mutations identified through a large screening program of subjects attending a
      health appraisal center. SUBJECTS AND METHODS: Presence of symptoms commonly
      associated with clinical hemochromatosis was ascertained by self-report on a
      written questionnaire among C282Y homozygotes and HFE wild-type subjects of white
      or Hispanic ethnicity identified from screening 41,599 adult subjects between
      March 1999 and August 2001. A subset of C282Y homozygotes and wild-type subjects
      identified from 12,756 subjects attending the center in the final year of the
      study completed a standardized double-blind interview with a physician regarding
      the presence, duration, and severity of a larger set of symptoms. Prevalence of
      symptoms among C282Y homozygotes and wild-type controls ascertained by written
      questionnaire and interview were compared by chi2 analysis or Fisher exact test.
      Symptoms among subjects with other combinations of the C282Y and H63D HFE
      mutations were also assessed by questionnaire. RESULTS: The 124 C282Y homozygotes
      who filled out the written questionnaire and the 17 C282Y homozygotes who
      completed the physician double-blind interview reported no significantly higher
      rates of arthritis or joint pain, abdominal pain, arrhythmias, darkening of skin,
      or other symptoms traditionally associated with hemochromatosis compared with the
      22,429 wild-type controls who filled out the written questionnaire and 29 wild
      type controls who completed the double-blind interview. The only symptom reported
      more frequently by C282Y homozygotes was loss of body hair, reported by 5
      C282Y/C282Y female subjects compared with 1 wild-type male subject (P=.02) in the
      physician interview. Symptoms among subjects with other HFE genotypes were
      similar to symptoms of wild-type subjects. CONCLUSIONS: Results of this study
      indicate that many of the symptoms associated with hemochromatosis are common
      among HFE wild types and that clinical penetrance of the C282Y/C282Y genotype in
      regard to these symptoms is low.

PMID- 12059122
TI  - Quality of life in patients with postural tachycardia syndrome.
AB  - OBJECTIVES: To quantify quality of life and identify demographic and clinical
      correlates of functioning in a well-characterized sample of patients with
      postural tachycardia syndrome (POTS). PATIENTS AND METHODS: Prospective patients
      were those seen at the Mayo Clinic Autonomic Disorders Laboratory from September
      2000 to June 2001. Neurologists made diagnoses of POTS according to established
      criteria. Patients completed a questionnaire packet that included measures of
      quality of life (36-Item Short-Form Health Survey [SF-36]) and symptom severity
      (Autonomic Symptom Profile). Additional clinical information was abstracted from
      medical records. RESULTS: Ninety-four patients (89% female; mean age, 34.2 years)
      were enrolled in the study. Patients with POTS reported impairment across
      multiple domains on the SF-36. Physical functioning, role functioning, bodily
      pain, general health, vitality, and social functioning were all significantly
      impaired compared with a healthy population (P<.01 for all) and similar to that
      reported by patients with other chronic, disabling conditions. Hierarchical
      regression analyses revealed that symptom severity (beta = -.36, P<.001) and
      disability status (beta = -36, P<.001) were independent predictors of SF-36
      physical component scores, with the full model accounting for 54% of the variance
      (P<.001). None of the variables examined accounted for a significant amount of
      the variance in SF-36 mental component scores. CONCLUSIONS: Patients with POTS
      experience clear limitations across multiple domains of quality of life,
      including physical, social, and role functioning. Treatment should address the
      multiple and varied impairments experienced by these patients and may require a
      multidisciplinary approach. Future research must further delineate factors, both
      disease related and psychosocial, that predict functioning and adjustment in this
      population.

PMID- 12059123
TI  - Cancer antigen 125 in patients with chronic liver disease.
AB  - OBJECTIVES: To determine the association between elevated levels of serum cancer
      antigen (CA) 125 and liver disease and to explore the possibility that CA 125 is
      produced by the peritoneum as a nonspecific response to the presence of fluid in
      the peritoneal cavity. PATIENTS AND METHODS: Between June and October 1992, CA
      125 levels were measured in serum stored from 50 consecutive patients with
      cirrhotic ascites, 20 patients with cirrhosis but without ascites, and 12
      patients with acute viral hepatitis without ascites. Serum CA 125 was also
      measured in 4 patients with chronic renal failure before and after initiation of
      continuous ambulatory peritoneal dialysis. RESULTS: Levels of CA 125 were
      elevated in patients with all forms of liver disease, especially in those with
      cirrhotic ascites irrespective of the etiology of cirrhosis or the presence of
      spontaneous bacterial peritonitis or hepatocellular carcinoma. Levels of CA 125
      did not change significantly 1 month after initiation of continuous ambulatory
      peritoneal dialysis. CONCLUSION: Cancer antigen 125 is elevated in patients with
      acute and chronic liver disease, especially in those with cirrhotic ascites. This
      elevation in CA 125 is not because of a nonspecific response of the peritoneum to
      fluid in the peritoneal cavity. Awareness of the association of elevated CA 125
      in patients with cirrhotic ascites can prevent unnecessary surgical intervention.

PMID- 12059124
TI  - Thrombolytic treatment of acute ischemic stroke.
AB  - Intravenous recombinant tissue-type plasminogen activator is approved by the US
      Food and Drug Administration for treating acute ischemic stroke within 3 hours of
      onset of symptoms. Initiation of thrombolysis within 90 minutes of onset of
      symptoms is a treatment goal supported by current studies. Postmarketing data
      suggest that the risk of intracranial hemorrhage may be unacceptably high when
      recombinant tissue-type plasminogen activator is given to patients who would not
      have been eligible for enrollment in the pivotal phase 3 clinical trials. Further
      studies of local intra-arterial thrombolysis and improved selection of patients
      with advanced brain imaging are expected in the future, but the emphasis at
      present should be on rapid identification, evaluation, and treatment of
      appropriate patients with intravenous therapy.

PMID- 12059125
TI  - Electroconvulsive therapy and newer modalities for the treatment of medication
      refractory mental illness.
AB  - Severe mental illnesses often remain chronic and refractory to medication,
      leading to substantial morbidity and mortality. For more than 60 years,
      electroconvulsive therapy has been the only nonpharmacological psychiatric
      procedure available to treat severe or medication-refractory major depressive
      disorder and other psychiatric conditions. Memory dysfunction remains the most
      serious adverse effect, and current research focuses on attempts to ameliorate
      this complication. Transcranial magnetic stimulation and vagus nerve stimulation,
      2 new neuropsychiatric technologies, are emerging as possible additions to our
      therapeutic armamentarium. Besides providing therapeutic benefits, these 3
      methods may help elucidate the pathophysiology of psychiatric illness.

PMID- 12059126
TI  - 31-year-old woman with confusion and labile behavior.

PMID- 12059127
TI  - Assessing meaningful change in quality of life over time: a users' guide for
      clinicians.
AB  - The objective of this article is to help clinicians interpret trial-based quality
      of life (QOL) changes over time. We address a series of questions and provide
      guidelines that are fundamental to assessing and interpreting change. The issues
      addressed are as follows: (1) What are the characteristics of the population for
      whom changes in QOL are reported? (2) Is the QOL questionnaire reliable, valid,
      and responsive to change? (3) Are the timing and frequency of assessments
      adequate? (4) Is the study adequately powered? (5) How are multiple QOL outcomes
      addressed in analyses? (6) How are multiple time points handled? (7) Can
      alternative explanations account for the observed change or lack of observed
      change (eg, handling of missing data, survival differences, and changes in
      patient's QOL perspective over time)? and (8) How is statistical significance
      translated into meaningful change? These guidelines will support clinicians in
      reviewing the clinical trial literature, which in turn can help them use the data
      in the treatment decision process.

PMID- 12059128
TI  - The clinical significance of quality-of-life results: practical considerations
      for specific audiences.
AB  - This is the sixth article in a series intended to summarize the state of the
      science for assessing the clinical significance of quality-of-life (QOL)
      assessments. The previous 5 articles dealt with specific methodological issues,
      whereas this article addresses practical considerations in implementing the
      methods and presenting the results to various audiences with differing
      perspectives. Proposals for how to interpret the "clinical significance" or
      "clinical meaningfulness" of changes in QOL scores were addressed in previous
      articles within this series. Within this article, 4 audiences-patients and
      physicians, clinical researchers, health policymakers, and private- and public
      sector employees who work in health-related fields-are examined because each is a
      unique stakeholder with a distinct vantage point and each can interpret QOL
      outcomes differently. A clinician may attempt to explain to a patient potential
      treatment alternatives for his or her QOL; a health policymaker may try to
      describe to elected officials the financial impact on a patient population with
      reduced QOL; a researcher may try to obtain the vital messages from a clinical
      trial that included QOL end points; and a regulatory agency and/or pharmaceutical
      company may try to ascertain the appropriate level of evidence required for a
      successful research study. For each of the 4 audiences, concrete examples and
      practical guidelines are offered by which changes in QOL outcomes can be
      interpreted meaningfully. Ultimately, both determining and disseminating the
      meaning of clinical significance are functions of the outlook of the audience
      because the perspective of the audience determines its ability to comprehend,
      evaluate, and convey the context within which such outcomes appear meaningful.
      Among the audiences described within this article, a commonality of interests
      exist that mandates a careful exposition of the scientific rigor involved in
      describing the clinical significance of QOL assessments. Collectively, this
      series attempts to provide methods and means for making such determinations.

PMID- 12059129
TI  - Hypocalcemia-like electrocardiographic changes after administration of
      intravenous fosphenytoin.
AB  - Fosphenytoin is a prodrug that is metabolized by phosphatases to yield the
      antiepileptic drug phenytoin plus inorganic phosphate. Thus, fosphenytoin can
      theoretically alter the electrocardiogram by 2 mechanisms: the direct effects of
      phenytoin on cardiac conduction and on phosphate binding of calcium, which could
      indirectly alter cardiac conduction as a result of hypocalcemia. We report the
      case of a 23-year-old man, weight 73 kg, with a known but untreated seizure
      disorder who was given prophylactic fosphenytoin, 1500-mg phenytoin equivalents
      over 85 minutes by intravenous infusion. The patient was normocalcemic before
      drug infusion. Fosphenytoin produced electrocardiographic changes (prolongation
      of the ST segment and the QT interval and merging of the T and P waves)
      consistent with hypocalcemia, and these changes were associated with new-onset
      reductions in both total and ionized serum calcium concentrations. Plasma
      phenytoin concentrations were within the therapeutic range during the
      electrocardiographic changes, and the patient's blood pressure was stable. We
      interpret these findings as fosphenytoin-related electrocardiographic changes
      likely attributable to inorganic phosphate-induced hypocalcemia.

PMID- 12059130
TI  - Symptomatic hyperthyroidism in a patient taking the dietary supplement
      tiratricol.
AB  - An 87-year-old woman was referred for evaluation of nervousness, tremor,
      insomnia, and fatigue of 2 months' duration. Initial laboratory evaluation
      revealed a suppressed thyrotropin level and an elevated triiodothyronine level. A
      review of her medications revealed that she had started taking several dietary
      supplements at the recommendation of her chiropractor before the onset of
      symptoms. One of these was tiratricol (3,5,3'-triiodothyroacetic acid or Triac),
      a substance sold as a dietary supplement despite classification as a drug by the
      Food and Drug Administration. Tiratricol has weak thyromimetic effects, can
      inhibit pituitary thyrotropin secretion, and in higher doses can significantly
      stimulate metabolism. Such was the case with this patient who presented with
      signs, symptoms, and biochemical evidence of hyperthyroidism that promptly
      resolved after discontinuation of tiratricol therapy. To our knowledge, this is
      the first reported case of documented thyrotoxicosis secondary to tiratricol use.
      Because tiratricol is still available for sale on several Internet sites, this
      case emphasizes the importance of inquiring about the use of dietary supplements
      in all patients. The availability of such products on the Internet increases the
      already complex task of monitoring patients' use of dietary supplements.

PMID- 12059131
TI  - Isolated metastatic myocardial carcinoid tumor in a 48-year-old man.
AB  - This brief report describes an asymptomatic patient with a myocardial mass. Two
      dimensional echocardiography, technetium Tc 99m cardiac nuclear scan, and
      transesophageal echocardiography were performed to define the mass. The mass,
      which involved the subvalvar right ventricular free wall, was resected and
      determined to be a metastatic carcinoid tumor by histologic and
      immunohistochemical analysis. Further investigation revealed the presence of a
      midgut carcinoid tumor located within the terminal ileum, which was also resected
      surgically. The patient recovered well after surgery and adjunctive chemotherapy.
      To our knowledge, this is the first report of comprehensive nuclear and
      echocardiographic imaging, supplemented by surgical and pathologic findings, in
      an asymptomatic patient with isolated myocardial metastasis of an ileal carcinoid
      tumor.

PMID- 12059132
TI  - Fatal tumor thrombosis due to an inferior vena cava leiomyosarcoma in a patient
      with antiphospholipid antibody syndrome.
AB  - We describe a patient with antiphospholipid antibody syndrome (APS) who died
      because of relentless inferior vena cava (IVC) tumor thrombosis due to an
      unsuspected leiomyosarcoma. Laboratory confirmation for APS was provided by
      functional identification of a lupus anticoagulant and anticardiolipin IgG and
      anti-beta2-glycoprotein I IgM antibodies. Although sensitive for detecting
      vascular obstruction, radiocontrast venography and magnetic resonance imaging and
      angiography detected the IVC thrombosis but failed to distinguish its malignant
      nature. Concomitant refractory thrombocytopenia prevented further invasive
      diagnostic and therapeutic maneuvers for progressive, severe IVC thrombosis
      unresponsive to aggressive treatment of APS. Deep venous thrombosis refractory to
      anticoagulant and immunomodulatory therapies in a patient with APS may be due to
      a concomitant underlying malignancy, such as a leiomyosarcoma, causing vascular
      obstruction.

PMID- 12059133
TI  - Religion and health.

PMID- 12059134
TI  - Religion and health.

PMID- 12059135
TI  - Deactivation of the biological activity of paraquat in the soil environment: a
      review of long-term environmental fate.
AB  - During the many years of paraquat usage, wide ranges of investigations of its
      environmental impact have been conducted. Much of this information has been
      published, but key, long-term field studies have not previously been presented
      and assessed. The purpose of this review is to bring together and appraise this
      information. Due to the nature of paraquat residues in soils, the major part
      (some 99.99%) of a paraquat application that reaches the soil within the typical
      Good Agricultural Practice (GAP) is strongly adsorbed to soils of a wide variety
      of textures. This is in equilibrium with an extremely low concentration in soil
      solution. However, the paraquat in soil solution is intrinsically biodegradable,
      being rapidly and completely mineralized by soil microorganisms. The deactivation
      of the biological activity of paraquat in soils, due to sorption, has been
      investigated thoroughly and systematically. It is recognized that the
      determination of total soil residues by severe extraction procedures provides no
      insight into the amount of paraquat biologically available in soil. Consequently,
      the key assay developed for this purpose, namely, the strong adsorption capacity
      wheat bioassay (SAC-WB) method, has proved to be valuable for determination of
      the adsorption capacity relevant to paraquat for any particular soil. This method
      has been validated in the field with a series of long-term (>10 years) trials in
      different regions of the world. These trials have also shown that, following
      repeated applications of very high levels of paraquat in the field, residues not
      only reach a plateau but also subsequently decline. This demonstrates that the
      known biodegradation of paraquat in soil pore water plays an important role in
      field dissipation. The biological effects of paraquat in the field have been
      assessed under unrealistically high treatment regimes. These trials have
      demonstrated that the continued use of paraquat under GAP conditions will have no
      detrimental effects on either crops or soil-dwelling flora and fauna. Any such
      effects can occur only under extreme use conditions (above the SAC-WB), which do
      not arise in normal agricultural practice.

PMID- 12059136
TI  - Determination of anthraquinone in technical material, formulations, and lettuce
      by high performance liquid chromatography.
AB  - Foraging on lettuce seeds and seedlings by horned larks (Eremophila alpestris)
      causes millions of dollars in losses to the California lettuce crop annually.
      Anthraquinone (AQ; 9,10-anthracenedione) has been shown to deter pest birds from
      consuming the seeds and seedlings of several plant species and was evaluated as a
      repellent to horned larks when applied to lettuce seedlings. A set of analytical
      methods using simple liquid extraction followed by high-performance liquid
      chromatography analysis were developed for the quantitation of AQ as technical
      material, as an active ingredient in a commercial formulation, and as a residue
      in lettuce plants. The methods were easy, reliable, and repeatable. AQ recoveries
      from control formulation fortified to concentrations of either 24 or 600 mg g(
      )(1) were 99 (+/-1.2%) and 98% (+/-1.2%), respectively, with a control
      formulation method limit of detection (MLOD) of 0.50 mg g(-)(1). Control lettuce
      tissues from three growth stages were AQ-fortified to concentrations of 0.50 and
      500 microg g(-)(1). The resulting AQ recoveries for the two fortification levels
      were 99 (+/-8.5) and 89% (+/-1.5%) for 11 day old seedlings, 95 (+/-2.6%) and 86%
      (2.1%) for 16 day old plants, and 92 (+/-1.4%) and 93% (+/-1.1%) for adult head
      lettuce cover leaves, respectively. The MLODs for the same three lettuce tissues
      were 0.055, 0.058, and 0.077 microg g(-)(1), respectively. These methods were
      used to quantify AQ residues from field-grown, treated lettuce and associated
      fortified quality control samples.

PMID- 12059137
TI  - New approach to immunochemical determinations for triclopyr and 3,5,6-trichloro-2
      pyridinol by using a bifunctional hapten, and evaluation of polyclonal antiserum.
AB  - The present work describes the design and synthesis of the structurally unique
      hapten, "bifunctional hapten", to produce a group-specific polyclonal antiserum
      to triclopyr and 3,5,6-trichloro-2-pyridinol. A bifunctional hapten was designed
      and synthesized by conjugating commercially available Nepsilon-2,4-dinitrophenyl
      (DNP)-L-lysine to triclopyr, and then coupling this to carrier proteins such as
      bovine serum albumin (BSA). The synthesized bifunctional hapten greatly raised
      the antiserum titer in comparison with that of the conventional hapten,
      triclopyr. Antiserum with a sufficiently high titer to provide the determinations
      of targeted compounds was obtained only 63 days after the primary immunization.
      The obtained antiserum showed the highest affinity to triclopyr (IC(50) = 3.5 nM)
      and 3,5,6-trichloro-2-pyridinol (IC(50) = 5.1 nM) in homologous ELISA. The cross
      reactivities to various agrochemicals and some chlorinated phenolic compounds
      were determined. Significant cross-reactivity was found to the herbicide 2,4,5-T.
      The antiserum reacted to both triclopyr and its metabolite. Assay sensitivity was
      evaluated for effects of various assay conditions, including pH value and
      concentrations of organic solvents and detergents. Under optimized assay
      conditions, the quantitative working range of triclopyr ELISA was from 0.1 to 5.2
      ng/mL with a limit of detection (LOD) of 0.037 ng/mL, and an IC(50) of 0.72
      ng/mL. On the other hand, the quantitative working range of 3,5,6-trichloro-2
      pyridinol ELISA was from 0.13 to 6.0 ng/mL with a LOD of 0.052 ng/mL, and an
      IC(50) of 0.95 ng/mL. Water samples fortified with triclopyr or its metabolite at
      1, 5, and 10 ng/mL were directly analyzed without extraction and cleanup by the
      proposed ELISA. The mean recovery was 101.6%, and the mean coefficient of
      variation (CV) was 7.1% in the case of the triclopyr ELISA. In the case of the
      3,5,6-trichloro-2-pyridinol ELISA, the mean recovery was 99.8%, and the mean CV
      was 9.5%. The proposed ELISA turned out to be a powerful tool for monitoring of
      residual triclopyr or 3,5,6-trichloro-2-pyridinol in water samples at trace
      level.

PMID- 12059138
TI  - Automatic flow system with voltammetric detection for diacetyl monitoring during
      brewing process.
AB  - Diacetyl can be determined by adsorptive stripping voltammetry after
      derivatization with o-phenylenediamine. The method may be applicable to the
      determination of diacetyl in different foods, being a good alternative to other
      analytical methods. In this work an on-line automated analytical system for
      diacetyl determination in beer is described. A hanging mercury drop electrode
      voltammetric flow detector was used, and the analyte was determined without the
      traditional deoxygenation procedure. The method was successfully applied to the
      determination of diacetyl during beer fermentation and in the final product. The
      automation strategy used was based on a flow network similar to those used in
      multicommutated flow systems, with a pervaporation unit used for diacetyl
      separation. The developed system was tested in real conditions in the monitoring
      of brewing processes. The results obtained were similar to those obtained with
      the usual GC-ECD methodology in the 5-600 ppb range. The analytical rate of the
      developed method is about 12 determinations/h.

PMID- 12059139
TI  - Validation of a method for the analysis of iron and manganese in table olives by
      flame atomic absorption spectrometry.
AB  - There is no generally accepted method for determination of the amounts of iron
      and manganese in table olives. Application of flame atomic absorption
      spectrometry to the analysis of both elements has been examined to validate a
      method that may be used by the industry's quality control laboratory as well as
      by the laboratories of regulatory agencies. The method has detection limits of
      0.106 and 0.022 mg/L and quantification limits of 0.271 and 0.057 mg/L, for Fe
      and Mn, respectively, referred to the solution to be measured. There was no
      significant effect due to the matrix, but a slight bias due to the presence of Ca
      has been detected. Recoveries were excellent, and the method was robust.
      Influence of operator, HCl and Mg salt compounds, calcination equipment, or dates
      on results was not found. Relative errors were, in general, below 4% for both
      cations, and repeatability was below 3.43 and 0.38 mg/kg of olive paste for Fe
      and Mn, respectively. The method is proposed for the analysis of Fe and Mn in
      ripe olives and table olives in general.

PMID- 12059140
TI  - Determination of free and total phenolic acids in plant-derived foods by HPLC
      with diode-array detection.
AB  - A high-performance liquid chromatographic (HPLC) method with diode-array
      detection (DAD) was used to identify and quantify free and total phenolic acids
      (m-hydroxybenzoic acid, p-hydroxybenzoic acid, protocatechuic acid, gallic acid,
      vanillic acid, syringic acid, o-coumaric acid, m-coumaric acid, p-coumaric acid,
      caffeic acid, ferulic acid, sinapic acid, chlorogenic acid, and ellagic acid) in
      plant foods. Free phenolic acids were extracted with a mixture of methanol and
      10% acetic acid. Bound phenolic acids were liberated using first alkaline and
      then acid hydrolysis followed by extraction with diethyl ether/ethyl acetate
      (1:1). All fractions were quantified separately by HPLC. After HPLC
      quantification, results of alkali and acid hydrolysates were calculated to
      represent total phenolic acids. Ellagic acid was quantified separately after long
      (20 h) acid hydrolysis. The methods developed were effective for the
      determination of phenolic acids in plant foods. DAD response was linear for all
      phenolic acids within the ranges evaluated, with correlation coefficients
      exceeding 0.999. Coefficients of variation for 4-8 sample replicates were
      consistently below 10%. Recovery tests of phenolic acids were performed for every
      hydrolysis condition using several samples. Recoveries were generally good (mean
      >90%) with the exceptions of gallic acid and, in some cases, caffeic acid
      samples.

PMID- 12059141
TI  - Improved HPLC method for the determination of curcumin, demethoxycurcumin, and
      bisdemethoxycurcumin.
AB  - Commercially available curcumin, a bright orange-yellow color pigment of
      turmeric, consists of a mixture of three curcuminoids, namely, curcumin,
      demethoxycurcumin, and bisdemethoxycurcumin. These were isolated by column
      chromatography and identified by spectroscopic studies. The purity of the
      curcuminoids was analyzed by an improved HPLC method. HPLC separation was
      performed on a C(18) column using three solvents, methanol, 2% AcOH, and
      acetonitrile, with detection at 425 nm. Four different commercially available
      varieties of turmeric, namely, Salem, Erode, Balasore, and local market samples,
      were analyzed to detect the percentage of these three curcuminoids. The
      percentages of curcumin, demethoxycurcumin, and bisdemethoxycurcumin as estimated
      using their calibration curves were found to be 1.06 +/- 0.061 to 5.65 +/- 0.040,
      0.83 +/- 0.047 to 3.36 +/- 0.040, and 0.42 +/- 0.036 to 2.16 +/- 0.06,
      respectively, in four different samples. The total percentages of curcuminoids
      are 2.34 +/- 0.171 to 9.18 +/- 0.232%.

PMID- 12059142
TI  - Phytochemical variation in echinacea from roots and flowerheads of wild and
      cultivated populations.
AB  - Quantitative phytochemical variation was determined from roots and inflorescences
      of native plant populations in the genus Echinacea. Specimens were collected in
      situ throughout the natural range of each putative taxon and transplanted to
      greenhouse cultivation. Ethanolic extracts from individual plants were separated
      by reversed-phase HPLC to quantify the alkamides, polyenes/ynes, and phenolics,
      and then grouped by age and taxonomically, according to a recent morphometric
      taxonomic revision of the genus. Canonical discriminant analysis revealed that
      cichoric acid, the diene alkamides 1-3 and 7, and ketoalkene 24 were the best
      taxonomic markers. Mean content for each of 26 phytochemicals revealed useful
      agronomic information, such as those varieties and organs with the highest
      accumulations, as well as the optimal age and growth conditions for each variety.
      The highest amounts of cichoric acid were measured from the older, wild
      inflorescences of E. pallida var.sanguinea, whereas the highest quantities of the
      alkamides 1-3 and 7 were present in roots of wild and transplanted E. purpurea.
      Baseline phytochemical data and chromatographic profiles for all types of wild
      Echinacea may be used for protection of wild stands, germplasm identification,
      and crop improvement.

PMID- 12059143
TI  - Biophenols in table olives.
AB  - Unprocessed olives are well-known sources of phenolic antioxidants with important
      biological properties. Processing methods to prepare table olives may cause a
      reduction of valuable phenols and may deprive the food of precious biological
      functions. The present work was undertaken to evaluate table olives produced in
      Greece as sources of biophenols. Commercially available olives were analyzed for
      their total phenol content by using the Folin-Ciocalteu reagent and for
      individual phenols by RP-HPLC. Samples were Spanish-style green olives in brine,
      Greek-style naturally black olives in brine, and Kalamata olives in brine. Most
      of the types of olives analyzed were found to be good sources of phenols.
      Hydroxytyrosol, tyrosol, and luteolin were the prevailing phenols in almost all
      of the samples examined. High levels of hydroxytyrosol were determined mainly in
      Kalamata olives and Spanish-style green olives, cultivar Chalkidiki (250-760
      mg/kg).

PMID- 12059145
TI  - Effect of roasting on the antioxidant activity of coffee brews.
AB  - Colombian Arabica coffee beans were roasted to give light, medium, and dark
      samples. Their aqueous extracts were analyzed by gel filtration chromatography,
      UV-visible spectrophotometry, capillary electrophoresis, and the ABTS(*)(+)
      assay. A progressive decrease in antioxidant activity (associated mainly with
      chlorogenic acids in the green beans) with degree of roasting was observed with
      the simultaneous generation of high (HMM) and low molecular mass (LMM) compounds
      possessing antioxidant activity. Maximum antioxidant activity was observed for
      the medium-roasted coffee; the dark coffee had a lower antioxidant activity
      despite the increase in color. Analysis of the gel filtration chromatography
      fractions showed that the LMM fraction made a greater contribution to total
      antioxidant activity than the HMM components.

PMID- 12059144
TI  - Inhibition of low-density lipoprotein oxidation and up-regulation of low-density
      lipoprotein receptor in HepG2 cells by tropical plant extracts.
AB  - Twelve edible plant extracts rich in polyphenols were screened for their
      potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to
      modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant
      activity (inhibition of LDL oxidation) was determined by measuring the formation
      of conjugated dienes (lag time) and thiobarbituric acid reagent substances
      (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf
      (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle
      calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and
      inhibition of TBARS formation (P < 0.05) compared to control. LDLr was
      significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%),
      cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts
      studied demonstrated a positive association between antioxidant activity and the
      ability to up-regulate LDL receptor. Findings suggest that reported protective
      actions of plant polyphenols on lipoprotein metabolism might be exerted at
      different biochemical mechanisms.

PMID- 12059146
TI  - Novel derivatives of ent-17,19-dihydroxy-16betaH-kaurane obtained by
      biotransformation with Verticillium lecanii.
AB  - In the search for new routes in the synthesis of hydroxylated kaurane
      diterpenoids, Verticillium lecanii, grown in a mineral liquid medium for 48 h,
      was fed with ent-17,19-dihydroxy-16betaH-kaurane, obtained by
      hydroboration/oxidation of kaurenoic acid, a natural product easily isolated from
      plants of the genera Xylopia (Annonaceae) and Wedelia (Asteraceae). After 14
      days, the culture medium was extracted with ethyl acetate, and the metabolites
      were purified by column chromatography on silica gel. The results show that V.
      lecanii biotransformed the starting material into three novel compounds: ent
      11alpha,17,19-trihydroxy-16betaH-kaurane; ent-7alpha,17,19-trihydroxy-16betaH
      kaurane; and ent-7beta,17,19-trihydroxy-16betaH-kaurane, the structures of which
      were fully elucidated by using classical and modern two-dimensional NMR
      techniques.

PMID- 12059147
TI  - Antioxidant activity of prune (Prunus domestica L.) constituents and a new
      synergist.
AB  - Ethanol extract of prune was separated into hexane-soluble and H(2)O-soluble
      fractions, and the H(2)O-soluble fraction was further separated into a methanol
      (MeOH) eluate and an H(2)O eluate by Diaion HP-20 column chromatography. The MeOH
      eluate exhibited the strongest antioxidant activity among the separated fractions
      evaluated by oxygen radical absorbance capacity (ORAC). Further purification of
      the MeOH eluate led to isolation of a novel compound, 4-amino-4-carboxychroman-2
      one, together with four known compounds (p-coumaric acid, vanillic acid beta
      glucoside, protocatechuic acid, and caffeic acid), structures of which were
      identified by NMR and MS analyses. The ORAC values of these isolated compounds
      showed 0.15-1.43 units (micromol of Trolox equiv)/micromol, and the new compound
      showed a remarkable synergistic effect on caffeoylquinic acid isomers. The
      antioxidant activity of the MeOH eluate was highly dependent on the major prune
      components, caffeoylquinic acid isomers, with a contribution from the new
      synergist.

PMID- 12059149
TI  - Identification and characterization of foliar polyphenolic composition in
      sweetpotato (Ipomoea batatas L.) genotypes.
AB  - Trials over two years were conducted using 1389 sweetpotato (Ipomoea batatas L.)
      genotypes collected from all over the world to characterize the polyphenolic
      composition in sweetpotato leaves. Wide variation was observed in relation to
      their total and individual leaf polyphenolic constituents. In all genotypes
      studied, the total polyphenol contents of sweetpotato leaf ranged from 1.42 to
      17.1 g/100 g dry weight. The six different polyphenolic compounds were identified
      and quantified by NMR, FABMS, and RPHPLC analysis procedures. This is the first
      report of polyphenolic compositions in sweetpotato leaves. The relative levels of
      polyphenolic acids in sweetpotato leaves were as follows: 3,5-di-O-caffeoylquinic
      acid > 4,5-di-O-caffeoylquinic acid > chlorogenic acid (3-O-caffeoylquinic acid)
      > 3,4-di-O-caffeoylquinic acid > 3,4,5-tri-O-caffeoylquinic acid > caffeic acid.
      The highest 3,4,5-tri-O-caffeoylquinic acid and 4,5-di-O-caffeoylquinic acid
      occurred at 221 and 1183.30 mg/100 g dry weight, respectively.

PMID- 12059148
TI  - Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals.
AB  - To express the antioxidant capacity of plant foods in a more familiar and easily
      understood manner (equivalent to vitamin C mg/100 g), two stable radical species,
      ABTS(*)(-) and DPPH(*), commonly used for antioxidant activity measurements, were
      employed independently to evaluate their efficacies using apple polyphenolic
      extracts and seven polyphenolic standards including synthetic Trolox. Their
      antioxidant activities were expressed as vitamin C equivalent antioxidant
      capacity (VCEAC) in mg/100 g apple or mg/100 mL of the reference chemical
      compounds in 10 and 30 min using the ABTS(*)(-) and DPPH(*) scavenging assays,
      respectively. The antioxidant capacity of Gala apples and seven phenolic
      standards, determined by both ABTS(*)(-) and DPPH(*) scavenging assays, showed a
      dose-response of the first-order. Fresh Gala apples had a VCEAC of 205.4 +/- 5.6
      mg/100 g using the ABTS assay, and the relative VCEACs of phenolic standards were
      as follows: gallic acid > quercetin > epicatechin > catechin > vitamin C > rutin
      > chlorogenic acid > Trolox. With the DPPH radical assay, the VCEAC of fresh Gala
      apples was 136.0 +/- 6.6 mg/100 g, and the relative VCEACs of seven phenolic
      standards were, in decreasing order, as follows: gallic acid > quercetin >
      epicatechin > catechin > or = vitamin C > Trolox > rutin > chlorogenic acid.
      Because the ABTS assay can be used in both organic and aqueous solvent systems,
      employs a specific absorbance at a wavelength remote from the visible region, and
      requires a short reaction time, it is a more desirable method than the DPPH
      assay. Therefore, it is recommended that antioxidant capacity be expressed as
      vitamin C mg/100 g equivalent (VCEAC) using the ABTS assay.

PMID- 12059150
TI  - Immobilization and utilization of the recombinant fusion proteins trypsin
      streptavidin and streptavidin-transglutaminase for modification of whey protein
      isolate functionality.
AB  - A method was developed for the production of a hydrolyzed/polymerized whey
      protein derivative with altered solution and gelation properties using a
      combination of recombinant DNA and immobilized enzyme technologies. The
      recombinant fusion proteins trypsin-streptavidin (TrypSA) and streptavidin
      transglutaminase (cSAcTG) were produced in Escherichia coli, extracted, and then
      immobilized by selective adsorption on biotinylated controlled-pore glass.
      Recirculation through a TrypSA reactor induced limited proteolysis of whey
      proteins. Hydrolysates were then recirculated through a cSAcTG reactor for
      incremental periods of time to arrive at increasing degrees of polymerization.
      The polymers were subsequently analyzed for viscosity/flow behavior, gelation
      properties, and fracture properties using shear rate ramps/intrinsic viscosity,
      small-strain oscillatory rheology, and vane viscometry, respectively. By
      combining limited proteolysis with controlled cross-linking, it was possible to
      create derivatives of whey proteins with enhanced functional properties.
      Increases in the degree of whey protein modification were correlated with greater
      apparent viscosity and intrinsic viscosity, lowered gel point temperatures, and
      stronger, more brittle gels. This method allowed for recycling of the enzyme,
      eliminated the requirement for a downstream inactivation step, and permitted
      control over the extent of modification. Utilization of a similar process may
      allow for the production of designer proteins engineered with specific
      functionalities.

PMID- 12059151
TI  - Enhanced expression of chicken cystatin as a thioredoxin fusion form in
      Escherichia coli AD494(DE3)pLysS and its effect on the prevention of surimi gel
      softening.
AB  - The DNA encoding chicken lung cystatin was ligated into a thioredoxin-pET 23a+
      expression vector and transformed into Escherichia coli AD494(DE3)pLysS. A high
      level of soluble recombinant thioredoxin-cystatin (trx-cystatin) was expressed in
      the cytoplasm of the E. coli transformant. As compared with recombinant cystatin
      (trx-free), a 38.7% increase of inhibitory activity in the soluble fraction was
      achieved by introducing the trx fusion protein. Trx-cystatin was purified to
      electrophoretical homogeneity by 3 min of heating at 90 degrees C and Sephacryl S
      100 chromatography. The molecular mass of trx-cystatin was 29 kDa, which was the
      expected size based on its composition of recombinant trx (16 kDa) and chicken
      cystatin (13 kDa). The purified trx-cystatin behaved as a thermally stable and
      papain-like proteinase inhibitor comparable to either recombinant or natural
      chicken cystatins. The inhibitor could inhibit the gel softening of mackerel
      surimi.

PMID- 12059152
TI  - Effects of raw materials, ingredients, and production lines on arsenic and copper
      concentrations in confectionery products.
AB  - The Spaniard legislation sets up maximum levels for total arsenic (As) and copper
      (Cu) in confectionery products at 0.1 and 5.0 microg g(-)(1), respectively.
      Concentrations of these two trace elements were determined in four confectionery
      products: chewing gum, two licorice items, and soft candy. The effects of raw
      materials quality and production lines were studied. Arsenic and copper were
      quantified by atomic absorption spectrometry with hydride generation and slotted
      tube atom trap tubes, respectively. Their levels were, in general, below the
      maximum limits establish by the Spaniard legislation; however, the As
      concentration in the licorice sticks was above this maximum limit (0.11 +/- 0.01
      microg g(-)(1)). Statistics proved that quality of raw materials and the
      production lines both significantly affected As and Cu concentrations in the
      final products. The licorice extract and molasses were found as the common source
      for As and Cu pollution. The As concentration in the licorice extract was 0.503
      +/- 0.01 microg g(-)(1), and could represent a serious hazard to human health if
      it is used in high proportions.

PMID- 12059153
TI  - Factors affecting the formation of alkylpyrazines during roasting treatment in
      natural and alkalinized cocoa powder.
AB  - The cocoa roasting process at different temperatures (at 125 and 135 degrees C
      for 3 min, plus 44 and 52 min, respectively, heating-up times) was evaluated by
      measuring the initial and final free amino acids distribution, flavor index,
      formol number, browning measurement, and alkylpyrazines content in 15 cocoa bean
      samples of different origins. These samples were also analyzed in manufactured
      cocoa powder. The effect of alkalinization of cocoa was studied. Results
      indicated that the final concentration and ratio of
      tetramethylpyrazine/trimethylpyrazine (TMP/TrMP) increased rapidly at higher
      roasting temperatures. The samples roasted with alkalies (pH between 7.20 and
      7.92), such as sodium carbonate, or potassium plus air injected in the roaster
      during thermal treatment, exhibited a greater degree of brown color formation,
      but the amount of alkylpyrazines generated was adversely affected. The analysis
      of alpha-free amino acids at the end of the roasting process demonstrated the
      importance of the thermal treatment conditions and the pH values on nibs (cocoa
      bean cotyledons), liquor, or cocoa. Higher pH values led to a lower concentration
      of aroma and a higher presence of brown compounds.

PMID- 12059155
TI  - Synthesis, fungicidal activity, and 3D-QSAR of pyridazinone-substituted 1,3,4
      oxadiazoles and 1,3,4-thiadiazoles.
AB  - A series of novel 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl] -2
      arylamino-1,3,4-oxadiazoles, fungicidally active, were synthesized based on
      bioisosterism and tested in vivo against wheat leaf rust, Puccinia recondita.
      These compounds were shown to be fungicidally active, and their activity was
      influenced by the nature of the substituents. By using the three-dimensional
      quantitative structure-activity relationships (3D-QSAR) method of comparative
      molecular field analysis (CoMFA), we have studied the structure and activity
      relationship of the compounds containing both pyridazinone-substituted 1,3,4
      thiadiazoles and pyridazinone-substituted 1,3,4-oxadiazoles. The 3D-QSAR modes
      gave good correlation between the variations on percent inhibition and the steric
      electrostatic properties. The results are consistent with a common mode of action
      for the pyridazinone-substituted 1,3,4-thiadiazoles and the pyridazinone
      substituted 1,3,4-oxadiazoles, which further confirms that the 1,3,4-oxadiazole
      ring is a bioisosteric analogue of the 1,3,4-thiadiazole ring. These offer
      important structural insights into designing highly active compounds prior to
      their synthesis.

PMID- 12059154
TI  - Antioxidant activity of coffee model systems.
AB  - Coffee model systems prepared from combinations of chlorogenic acid (CGA),
      N(alpha)-acetyl-1-arginine (A), sucrose (S), and cellulose (C) were roasted at
      240 degrees C for 4 min prior to analysis by UV-visible spectrophotometry,
      capillary zone electrophoresis (CZE), and the ABTS radical cation decolorization
      assay. The A/CGA/S/C and A/S/C systems were also fractionated by gel filtration
      chromatography. Antioxidant activity of the systems showed a positive, nonlinear
      relationship with the amount of CGA remaining after roasting. Sucrose degradation
      was a major source of color in the heated systems. There was no relationship
      between antioxidant activity and color generation.

PMID- 12059156
TI  - Volatile compounds emitted by sclerotia of Sclerotinia minor, Sclerotinia
      sclerotiorum, and Sclerotium rolfsii.
AB  - Volatile compounds emitted by sclerotia of Sclerotinia minor, Sclerotinia
      sclerotiorum, and Sclerotium rolfsii were identified by solid phase
      microextraction followed by gas chromatography and mass spectometry. Both S.
      minor and S. sclerotiorum emitted 2-methylenebornane and 2-methylisoborneol. In
      addition, S. minor emitted mesityl oxide, gamma-butyrolactone, cis- and trans
      linalool oxide, linalool, and trans-nerolidol. S. sclerotiorum emitted 2-methyl-2
      bornene, 1-methylcamphene, and a diterpene with a molecular weight of 272.
      Sclerotium rolfsii did not emit any of these compounds but did emit delta
      cadinene and cis-calamenene. Chemicals emitted by S. minor and S. sclerotiorum
      were tested to determine if they could stimulate germination of conidia of
      Sporidesmium sclerotivorum, a mycoparasite on sclerotia of Sclerotinia spp.
      Chemicals were tested at 1 part per billion to 100 parts per million, both in
      direct contact with conidia and near, but not in, physical contact. None of the
      chemicals alone nor a combination of all chemicals induced germination of conidia
      of S. sclerotivorum.

PMID- 12059158
TI  - Principal component analysis of biogenic amines and polyphenols in Hungarian
      wines.
AB  - Biogenic amines, polyphenols, and resveratrol were analyzed quantitatively in 25
      different Hungarian wines from the same wine-making region, harvest of 1998.
      Polyphenols were determined according to a spectrophotometric method, whereas
      other substrates were analyzed using overpressured-layer chromatography (OPLC).
      Principal component analyses (PCA) were performed on data matrices consisting of
      substrates (columns) and different sorts of wines (rows) from the region of Pecs
      (southern Hungary). It was found that four (unrotated) principal components
      account for >80% of the total variance in the data. The plots of component
      loadings showed significant groupings for concentrations of biogenic amines (and
      polyphenols). Similarly, the component scores grouped according to the different
      sorts of wines. The loading plots reveal that there is no need to measure all of
      the variables to achieve the same characterization. It is enough to measure one
      variable per group. Naturally, this conclusion is valid only within the limits of
      the present study; wines from other regions may behave differently.

PMID- 12059157
TI  - A piperidine amide extracted from Piper longum L. fruit shows activity against
      Aedes aegypti mosquito larvae.
AB  - Mosquito larvicidal activity of Piper longum fruit-derived materials against the
      fourth-instar larvae of Aedes aegypti was examined. A crude methanol extract of
      P. longum fruits was found to be active against the larvae, and the hexane
      fraction of the methanol extract showed a strong larvicidal activity of 100%
      mortality. The biologically active component of P. longum fruits was
      characterized as pipernonaline by spectroscopic analyses. The LC(50) value of
      pipernonaline was 0.25 mg/L. The toxicity of pipernonaline is comparable to that
      of pirimiphos-methyl as a mosquito larvicide. In tests with available components
      derived from P. longum, no activity was observed with piperettine, piperine, or
      piperlongumine.

PMID- 12059159
TI  - Acylglycerol and fatty acid components of pulp, seed, and whole olive fruit oils.
      Their use to characterize fruit variety by chemometrics.
AB  - The contents of triacylglycerols and diacylglycerols in three kinds of olive
      fruit oils (pulp, seed, and whole fruit) were determined. The fatty acid
      composition and the quality ratios 1,2-diacylglycerols/1,3-diacylglycerols and
      1,2-diacylglycerols/total diacylglycerols were also assessed. Seven major Italian
      olive varieties were considered. Results of univariate statistical analyses
      indicated that the above analytical parameters (glyceridic ratios excepted) were
      effective in discriminating between pulp and seed oils. The seed oil fraction did
      not determine any change in the glyceridic indices and the acylglycerol or fatty
      acid composition concerning the whole fruit oil (mixture of pulp and seed oil
      fractions), the weight (%) of seed ( approximately 2%) being by far lower than
      the weight (%) of pulp ( approximately 85%) (fruit weight basis). Based on the
      data of triacylglycerol or fatty acid composition, and using appropriate
      parametric or nonparametric multivariate statistics, the genetic origins (olive
      variety) of the three fruit oil kinds were characterized.

PMID- 12059160
TI  - Comparison of content in phenolic compounds, polyphenol oxidase, and peroxidase
      in grains of fifty sorghum varieties from burkina faso.
AB  - Analysis of fifty sorghum [Sorghum bicolor (L.) Moench] varieties used in Burkina
      Faso showed that they have different contents of phenolic compounds, peroxidase
      (POX), and polyphenol oxidase (PPO). Most of the varieties (82%) had a tannin
      content less than 0.25% (w/w). POX specific activity was higher than the
      monophenolase and o-diphenolase specific activities of PPO. For POX, there was a
      diversity of isoforms among varieties. No clear correlation could be made between
      the quantitative composition of the grain in phenolics, PPO, and POX, and
      resistance of plant to pathogens. In general, varieties good for a thick porridge
      preparation ("to") had low phenolic compounds content and a medium POX activity.
      From the red varieties, those used for local beer ("dolo") had a high content in
      phenolic compounds and PPO, and a low POX activity. The variety considered good
      for couscous had a low POX content. The characteristics might be useful as
      selection markers for breeding for specific applications.

PMID- 12059161
TI  - Separation, characterization, and quantitation of benzoic and phenolic
      antioxidants in American cranberry fruit by GC-MS.
AB  - A GC-MS method is reported for separation and characterization of widely
      different amounts of benzoic and phenolic acids as their trimethylsilyl
      derivatives simultaneously in cranberry. Fifteen benzoic and phenolic acids
      (benzoic, o-hydroxybenzoic, cinnamic, m-hydroxybenzoic, p-hydroxybenzoic, p
      hydroxyphenyl acetic, phthalic, 2,3-dihydroxybenzoic, vanillic, o
      hydroxycinnamic, 2,4-dihydroxybenzoic, p-coumaric, ferulic, caffeic, and sinapic
      acid) were identified in cranberry fruit in their free and bound forms on the
      basis of GC retention times and simultaneously recorded mass spectra. Except for
      benzoic, p-coumaric, caffeic, ferulic, and sinapic acids, 10 other phenolic acids
      identified have not been reported in cranberry before. The quantitation of the
      identified components was based on total ion current (TIC). The experimental
      results indicated cranberry fruit contains a high content of benzoic and phenolic
      acids (5.7 g/kg fresh weight) with benzoic acid being the most abundant (4.7 g/kg
      fresh weight). The next most abundant are p-coumaric (0.25 g/kg fresh weight) and
      sinapic (0.21 g/kg fresh weight) acid. Benzoic and phenolic acids occur mainly in
      bound forms and only about 10% occurs as free acid.

PMID- 12059162
TI  - Dissipation of the defoliant tribufos in cotton-producing soils.
AB  - Soil dissipation of the cotton defoliant tribufos was measured in laboratory
      incubations and on 0.2-ha research plots. Computed 50% dissipation time (DT(50))
      using nonlinear and linear kinetic models ranged from 1 to 19 days. Data
      indicated that exchangeable soil aluminum inhibited tribufos-degrading soil
      organisms. Nevertheless, measured DT(50) values were 40 to 700 times less than
      the aerobic soil half-life (t(1/2)) values used in recent tribufos risk
      assessments. DT(50) values suggest that risk estimates were overstated. However,
      edge-of-field runoff concentrations measured on research plots exceeded
      invertebrate LOECs, thus some aquatic risk is indicated. Field data also
      suggested that volatilization may be a significant soil dissipation pathway. From
      this result, we conclude that volatilization should be included in simulation
      models used for pesticide registration. This will likely improve the accuracy of
      model outputs for products such as tribufos. Potential volatilization losses
      indicate a need to evaluate the atmospheric behavior of tribufos.

PMID- 12059163
TI  - Multivariate analysis of the influence of pectin, white syrup, and citric acid on
      aroma concentration in the headspace above pectin gels.
AB  - Pectin gels consist of polysaccharide networks surrounded by water. The gel
      networks can prevent release of aroma molecules from the gel to the gas phase
      above. In this study static headspace measurements were performed to correlate
      aroma concentration in the gas phase above pectin gels to different amounts of
      the gel ingredients. As a consequence, aroma concentration in the headspace in
      relation to gel texture, as characterized by rheology measurements, was also
      studied. Aroma concentration in the headspace above strong gels was low, due to
      entrapment of aroma molecules within the gel structure. Viscous solutions
      generally gave a high aroma concentration in the headspace, but owing to a
      complex matrix, this was lowered when large amounts of the gel ingredients were
      added. However, a high correlation between interaction terms and square terms of
      design variables and rheology parameters with aroma compounds indicated nonlinear
      and complex relationships.

PMID- 12059164
TI  - Optimization of headspace solid-phase Microextraction (SPME) for the odor
      analysis of surface-ripened cheese.
AB  - Fifty volatile compounds of surface smear-ripened cheese were detected and
      identified using headspace solid-phase microextraction (HS-SPME) and vacuum
      distillation coupled to gas chromatography-mass spectrometry. Changes in the
      headspace of aroma compounds were monitored over the whole packaging period (47
      days) using the HS-SPME method. Initially, the concentration of methanethiol
      increased before reaching a plateau. This evolution could be linked to the growth
      of Brevibacterium linens. During the shelf life of cheese, levels of acetic acid
      and 3-methylbutanoic acid remained constant, whereas butane-2,3-dione, 3
      hydroxybutan-2-one, and hydroxypropan-2-one levels gradually declined and acetone
      and 3-methylbutanol levels dropped sharply to a plateau. Changes in odor could be
      related to changes of the rind, which behaved as a barrier, strongly influencing
      the distribution of volatile compounds in the headspace. Using a gas
      chromatography-olfactometry technique without separation, it was shown that the
      SPME extract was representative of the cheese odor.

PMID- 12059166
TI  - Analysis of grape Vitis vinifera L. DNA in must mixtures and experimental mixed
      wines using microsatellite markers.
AB  - Because wine quality highly relies on the varietal composition of the must, the
      development of methods allowing the authentication of varieties in musts and
      wines would be of great value as a guarantee of quality. Microsatellite markers
      have already been applied to the authentication of grape juices (Faria, M. A.;
      Magalhaes, R.; Ferreira, M. A.; Meredith, C. P.; Ferreira Monteiro, F. J. Agric.
      Food Chem. 2000, 48, 1096-1100) and to the analysis of experimental wines (Siret,
      R.; Boursiquot, J. M.; Merle, M. H.; Cabanis, J. C.; This, P. J. Agric Food Chem.
      2000, 48, 5035-5040). In the present paper, we accessed the usefulness of this
      technology for the analysis of must and wine mixtures. The detection limit of DNA
      mixtures was first estimated on DNA extracted from leaves: 4% of a foreign DNA
      can be detected. Analysis of must and wine mixtures (Chardonnay B/Clairette B and
      Syrah N/Grenache N) was performed on experimental fermentations. DNA was
      extracted along the fermentation process and analyzed using five microsatellite
      loci. The 70:30 (v/v) mixtures were successfully analyzed until the end of the
      fermentation. The applications of these results to commercial purposes are
      discussed.

PMID- 12059165
TI  - Investigation of the beta-damascenone level in fresh and aged commercial beers.
AB  - This study investigated the increase of beta-damascenone content during aging in
      a variety of commercial Belgian beers. Quantities detected in fresh beers were
      generally low (from 6 ng/g to 25 ng/g). After 5 days at 40 degrees C, the level
      increased (to as much as 210 ng/g) in most of the beers studied, according to the
      type of beer. Further experiments showed that wort initially contains large
      quantities of beta-damascenone (450 ng/g), but that degradation of the compound
      during fermentation accounts for the low concentrations observed in fresh beers.
      Production during beer aging can be partially explained by acid hydrolysis of
      glycosides.

PMID- 12059167
TI  - Characterization of haze-active proteins in apple juice.
AB  - The nature of the haze-active protein (HAP) in apple juice was investigated. Heat
      treatment removed protein indiscriminately while polyvinylpolypyrrolidone (PVPP)
      treatment was fairly specific for proteins of 15 and 28 kDa. Presumably, the PVPP
      bound to polyphenols, which in turn were complexed with protein. Three candidate
      apple HAPs were isolated. Two were extracted from juice with acetone and
      fractionated by hydrophobic interaction chromatography and solid phase extraction
      with C18 (HAP I) or SAX (HAP II) material. Hydroxyproline-rich protein was
      extracted from apple tissue (HAP III). The order of haze formation with tannic
      acid was gliadin > HAP III > HAP II > HAP I > bovine serum albumin, which shows
      increasing haze formation with increasing proline content. The sizes of HAP I,
      II, and III were 28, 15, and 12 kDa; the first two corresponded to the sizes of
      proteins removed by PVPP treatment and are involved in juice haze formation.

PMID- 12059168
TI  - Hydroxytyrosol 4-beta-D-glucoside, an important phenolic compound in olive fruits
      and derived products.
AB  - There is increasing interest in olive polyphenols because of their biological
      properties as well as their contribution to the color, taste, and shelf life of
      olive products. However, some of these compounds remain unidentified. It has been
      shown that hydroxytyrosol 4-beta-D-glucoside (4-beta-D-glucosyl-3
      hydroxyphenylethanol) coeluted with hydroxytyrosol [(3,4-dihydroxyphenyl)ethanol]
      under reversed phase conditions in the phenolic chromatograms of olive pulp,
      vegetation water, and pomace of olive oil processing. A method to separate this
      compound from hydroxytyrosol by HPLC has been developed. The concentration of
      this glucoside increased in olive pulp with maturation and could be the main
      phenolic compound in mature olives. In contrast, the presence of this compound
      was not detected in olive oil by using HPLC-MS. The compound must be considered
      both in table olives and olive oil processing because of its glucose and
      hydroxytyrosol contribution to these products.

PMID- 12059169
TI  - Investigation of volatiles evolution during the alcoholic fermentation of grape
      must using free and immobilized cells with the help of solid phase
      microextraction (SPME) headspace sampling.
AB  - A biocatalyst was prepared by immobilization of Saccharomyces cerevisiae strain
      AXAZ-1 on delignified cellulosic material (DCM). Repeated batch fermentations
      were conducted using these biocatalysts and free cells, separately, at
      temperatures of 20, 15, and 10 degrees C. Solid phase microextraction (SPME) was
      used in monitoring the formation of volatile alcohols, acetate esters, and ethyl
      esters of fatty acids. The kinetics of volatile production were similar for free
      and immobilized cells. In all cases immobilized cells showed a better rate of
      volatile production, which was directly connected to sugar consumption. The main
      difference observed was in propanol production, which increased with temperature
      decrease for the immobilized cells, whereas it remained constant for the free
      ones. In the case of immobilized cells significant amounts of esters were also
      produced. It is well-known that esters contribute to the fruity aroma of wine. It
      was also established that SPME is a very sensitive, accurate, and reliable
      technique and can be used without any reservation in the characterization of
      volatile constituents of wine.

PMID- 12059170
TI  - Trypsin-like proteinase produced by Fusarium culmorum grown on grain proteins.
AB  - The fungal disease Fusarium head blight occurs on wheat (Triticum spp.) and
      barley (Hordeum vulgare L.) and is one of the worldwide problems of agriculture.
      It can be caused by various Fusarium species. We are characterizing the
      proteinases of F. culmorum to investigate how they may help the fungus to attack
      the grain. A trypsin-like proteinase has been purified from a gluten-containing
      culture medium of F. culmorum. The enzyme was maximally active at about pH 9 and
      45 degrees C, but was not stable under those conditions. It was stabilized by
      calcium ions and by the presence of other proteins. The proteinase was most
      stable at pH 6-7 at ambient temperatures, but was quickly inactivated at 50
      degrees C. It was strongly inhibited by p-amidino phenylmethylsulfonyl fluoride
      (p-APMSF), and soybean trypsin and Bowman-Birk inhibitors, and it preferentially
      hydrolyzed the peptide bonds of the protein substrate beta-purothionin on the C
      terminal side of Arg (mainly) and Lys residues. These characteristics show that
      it is a trypsin-like proteinase. In addition, its N-terminal amino acid sequence
      was 88% identical to that of the F. oxysporum trypsin-like enzyme. The proteinase
      hydrolyzed the D hordein and some of the C hordeins (the barley storage
      proteins). This enzyme, and a subtilisin-like proteinase that we recently
      purified from the same organism, possibly play roles in helping the fungus to
      colonize grains.

PMID- 12059171
TI  - Effects of food materials on removal of Allium-specific volatile sulfur
      compounds.
AB  - Effects of food materials were investigated on removal of several kinds of
      thiols, sulfides, and disulfides, which arise from vegetables of Allium species
      during food preparation and eating. Methanethiol, propanethiol, and 2
      propenethiol were captured by raw foods such as fruits, vegetables, and mushrooms
      or a mixture of their acetone powders and phenolic compounds. The odor of diallyl
      disulfide was remarkably reduced by kiwi fruit, spinach, cutting lettuce,
      parsley, basil, mushrooms, and, particularly, cow's milk, raw egg, boiled rice,
      and bovine serum albumin (BSA). This suggests that the removal of diallyl
      disulfide could be caused by a physical and chemical interaction between the
      disulfide and foods. Furthermore, milk and BSA captured propanethiol, 2
      propenethiol, dipropyl sulfide, diallyl sulfide, dimethyl disulfide, and dipropyl
      disulfide very well. An enzymatic degradation of diallyl disulfide by spinach and
      asparagus was also observed. These results demonstrate that the deodorization
      with foods is achieved by multiple actions including physical and chemical
      interaction between volatile sulfur compounds and foods, enzymatic degradation of
      disulfides, and addition of thiols to polyphenolic compounds, catalyzed by
      polyphenol oxidases or peroxidases.

PMID- 12059172
TI  - Evaluation of antioxidative activity of extracts from a brown seaweed, Sargassum
      siliquastrum.
AB  - Antioxidative activities of the extracts from Sargassum siliquastrum were
      determined using the inhibition of red blood cell (RBC) hemolysis induced by 2,2'
      azobis(2-amidinopropane) dihydrochloride (AAPH) radicals, suppression of lipid
      peroxidation using rat brain homogenate, and scavenging activity of superoxide
      radicals. The dichloromethane fraction isolated from the methanol crude extract
      by differential solvent extractions exhibited the strongest antioxidant activity
      in both RBC hemolysis and lipid peroxidation assays. This fraction was further
      fractionated into four subfractions F1-F4 by silica gel column chromatography. F1
      was found to be most effective in protecting RBC against AAPH radicals and in
      inhibiting lipid peroxidation. On the basis of thin-layer chromatography and UV
      and IR spectra analyses, all subfractions contained phenolic compounds. However,
      there was no correlation between the above antioxidant potency and total phenolic
      compounds estimated by using the Folin-Ciocalteau method.

PMID- 12059173
TI  - Assessment of selenium bioavailability from high-selenium spirulina subfractions
      in selenium-deficient rats.
AB  - It was previously found that the bioavailability of Se from Se-rich spirulina
      (SeSp) was lower than that from selenite or selenomethionine when fed to Se
      deficient rats. The present study examined the bioavailability of Se from SeSp
      subfractions: a pellet (P) issuing from the centrifugation of a suspension of
      broken SeSp and a retentate (R) resulting from ultrafiltration of the supernatant
      through a 30 kDa exclusion membrane. Animals were fed a torula yeast based diet
      with no Se (deficients) or supplemented with 75 microg of Se/kg of diet as sodium
      selenite (controls) for 42 days. Se-deficient rats were then repleted for 56 days
      with Se (75 microg/kg of diet) supplied as sodium selenite, SeSp, P, or R. During
      this period, controls continued to receive sodium selenite. Speciation of Se in
      subfractions showed that the majority was present in the form of high molecular
      weight compounds; free selenomethionine was only a minor constituent. Gross
      absorption of Se from sodium selenite, P, and R was not different and was higher
      than from SeSp. Only retentate allowed full replenishment of Se concentration in
      liver and kidney (as did sodium selenite) and glutathione peroxidase (GSHPx)
      activity in liver, kidney, plasma, and erythrocytes. The bioavailabilities of Se
      in retentate, as assessed by slope ratio analysis using selenite as a reference
      Se, were 89 and 112% in the tissue Se content and 106-133% in the GSHPx
      activities. SeSp and P exhibited a gross bioavailability of <100%. These results
      indicate that Se in retentate is highly bioavailable and represents an
      interesting source of Se for food supplementation.

PMID- 12059174
TI  - Calcium absorption from three salts and CaSO(4)-fortified bread in premenopausal
      women.
AB  - Two studies were conducted to measure calcium absorption from calcium sulfate
      fortified bread and three salts (calcium lactate, calcium carbonate, and calcium
      sulfate) in healthy premenopausal women using a crossover design. In study I,
      calcium fractional absorption levels from the three salts labeled with a stable
      isotope, 44Ca, were not significantly different (0.039-0.47) as determined by the
      fecal recovery method. In a second study, absorption of 45Ca from CaSO(4)
      fortified labeled bread or labeled milk was measured in serum exactly 5 h
      postingestion. Fractional calcium absorption was slightly but significantly
      greater from fortified bread than from milk (mean within subject difference =
      0.0675 +/- 0.016). Calcium sulfate is a bioavailable fortificant for white bread
      that compares favorably with milk and two other salts.

PMID- 12059175
TI  - Mycoflora and fumonisin contamination in Brazilian corn from sowing to harvest.
AB  - The present study aimed to analyze the mycoflora and potential mycotoxin
      contamination of soil and corn samples collected at different plant maturity
      stages in Capao Bonito and Ribeirao Preto, two regions of the State of Sao Paulo,
      Brazil. In addition, the data obtained were correlated with the occurrence of
      wind-dispersed fungi and the predominant climatic conditions of the two regions
      studied. Corn mycoflora profiles showed that Fusarium verticillioides prevailed
      in 35% of the samples from Capao Bonito and in 49% of the samples from Ribeirao
      Preto. Examination of wind-dispersed fungi also revealed a high incidence of F.
      verticillioides. Soil mycoflora analyses showed that Penicilliumwas the most
      prevalent genus, although F. verticillioides was present in 55.5% of Capao
      Bonito's samples and in 26.7% of Ribeirao Preto's samples. With respect to water
      activity, the corn kernels most contaminated with F. verticillioides had water
      activity levels of 0.70-0.80. HPLC analysis of fumonisins revealed that 88.5% of
      Capao Bonito's kernels were contaminated with fumonisin B(1) (FB(1)) (0.09-10.87
      microg/g) and 53.8% with fumonisin B(2) (FB(2)) (0.05-0.52 microg/g); Ribeirao
      Preto's kernels presented contamination levels of 93.5% for FB(1) (0.11-17.69
      microg/g) and 61.3% for FB(2) (0.05-5.24 microg/g). No aflatoxins were detected
      by thin-layer chromatography in corn grains of either region. The concomitant
      occurrence of F. verticillioides and fumonisins in most of the field corn assayed
      demonstrates the importance of an effective control of cultivation throughout the
      plant maturity stages.

PMID- 12059176
TI  - Phytoestrogen-low diet for endocrine disruptor studies.
AB  - Hormonally active chemicals (HACs) that are capable of inducing adverse effects
      on wildlife as well as human beings are featured as "endocrine disruptors".
      Various animal studies conducted to clarify the characteristics of HACs,
      including the uterotrophic assay, are sufficiently sensitive to detect the effect
      of 17-beta-estradiol in micrograms per kilogram of body weight or lower. In such
      systems, a trace amount of HACs in the dietary pellets may interfere with the
      test results and thus can be a serious problem for the low-dose issue, which is
      now a major topic in the field of endocrine disruptor research. Here, the
      significance of the hormonal effects of phytoestrogen components in the NIH-07
      diet is confirmed and a NIH-07-based open formula "phytoestrogen-low diet" (PLD)
      is proposed, which effectively reduces uterine weight as well as the uterine
      luminal epithelial labeling index in ovariectomized rats.

PMID- 12059178
TI  - Hydrogen-bonding dynamics in photoinduced electron transfer in a ferrocene
      quinone linked dyad with a rigid amide spacer.
AB  - A newly designed ferrocene-quinone dyad with an amide space (Fc-Q) is employed to
      examine formation of the hydrogen bonding in the one-electron reduced form (Q*-)
      and the dynamics in the photoinduced electron-transfer reaction from the
      ferrocene to the quinone moiety. Photoexcitation of the Q moiety in Fc-Q in
      deaerated PhCN with 388 nm results in intramolecular electron transfer from Fc to
      the singlet excited state of Q to produce Fc+-Q*- without changing the
      conformation (<1 ps), followed by hydrogen bond formation with the amide proton
      of the spacer (tau = approximately 5 ps). The resulting radical ion pair decays
      via a back electron transfer to the ground state at a longer time scale with a
      rate constant of 2.6 x 108 s-1.

PMID- 12059179
TI  - Oxo, sulfido, and tellurido Mo-enedithiolate models for xanthine oxidase:
      understanding the basis of enzyme reactivity.
AB  - The active site of the mononuclear molybdenum enzyme xanthine oxidase has an
      LMoOS(OH) center that catalyzes the hydroxylation of substrate (L representing an
      enedithiolate ligand contributed by a pterin cofactor in the enzyme). Reaction of
      the enzyme with cyanide results in the replacement of the Mo=S group with a
      second Mo=O group, which results in loss of enzyme activity. To understand the
      basis for this loss of activity, we have computationally examined the interaction
      of a model for the LMoO2(OH) as well the LMoOTe(OH) congener of the enzyme with
      formamide (a substrate for the enzyme). Our electronic structure calculations for
      the oxo congener indicate a reduced electron density on the hydrogen being
      transferred from substrate in the course of the reaction, a shorter O-H bond in
      the transition state, and a longer nascent O-C bond of product, factors which
      combine to account for the loss of reactivity in the LMoO2(OH) species.
      Interestingly, our calculations indicate that the Te congener is characterized by
      an increased electron density on the hydrogen species being transferred, a longer
      Te-H bond in the transition state, and a shorter O-C nascent bond in the product
      and suggest that a Te congener of xanthine oxidase, were it to be prepared
      experimentally, should exhibit catalytic activity.

PMID- 12059180
TI  - The first direct and enantioselective cross-aldol reaction of aldehydes.
AB  - The first enantioselective catalytic direct cross-aldol reaction that employs
      nonequivalent aldehydes has been accomplished using proline as the reaction
      catalyst. Structural variation in both the aldol donor (R1 = Me, n-Bu, Bn, 91 to
      >99%) and aldol acceptor (R2 = I-Pr, I-Bu, c-C6H11, Et, Ph, 97-99% ee) are
      possible while maintaining high reaction efficiency (75-88% yield).
      Significantly, this new aldol variant allows facile enantioselective access to a
      broad range of beta-hydroxy aldehydes which are valuable intermediates in
      polyketide syntheses.

PMID- 12059181
TI  - Formation of alkylsilane-based monolayers on gold.
AB  - The formation of monolayers of alkylsilanes on a gold surface is characterized by
      X-ray photoelectron and reflection-absorption infrared spectroscopies. The
      reaction occurs through the activation of multiple Si-H bonds. Reactivity of the
      newly synthesized systems to oxygen and water is reported.

PMID- 12059183
TI  - Five-coordinate platinum(IV) complex as a precursor to a novel Pt(II) olefin
      hydride complex for alkane activation.
AB  - The five-coordinate platinum(IV) complex (nacnac)PtMe3 (nacnac- = [{(o
      iPr2C6H3)NC(CH3)}2CH]-) thermally eliminates ethane and methane to produce a
      novel olefin(hydrido)platinum(II) complex, where the olefin is part of the nacnac
      type ligand. This Pt(II) product activates hydrocarbons, including alkanes under
      mild conditions, as indicated by scrambling of hydrogen and deuterium between the
      hydrocarbon solvent and selected positions on the ligand of the platinum complex.
      A mechanism in which olefin insertion into the metal hydride bond opens a site to
      allow hydrocarbon coordination and C-H bond oxidative addition is proposed.

PMID- 12059182
TI  - N(2)-phenyldeoxyguanosine: modulation of the chemical properties of
      deoxyguanosine toward one-electron oxidation in DNA.
AB  - We have shown here that (1) substitution of an exocyclic amino group of dG is
      effective in modulating the chemical properties of dG toward one-electron
      oxidation and (2) decomposition of the guanine radical cation was effectively
      suppressed near dPhG. These results indicate that dPhG is a prototype of
      nucleosides functioning as an intrinsic antioxidant of duplex DNA toward one
      electron oxidation.

PMID- 12059184
TI  - Stable (amino)(phosphino)carbenes: difunctional molecules.
AB  - (Amino)(phosphino)carbenes are stable due to the donation of the nitrogen lone
      pair, the phosphino group remains strongly pyramidalized. Reactions can be
      performed selectively at the carbene center, but also at the phosphorus center
      leading to new stable carbenes. These difunctional molecules can be considered as
      hybrid ligands.

PMID- 12059185
TI  - Approaching exponential growth with a self-replicating peptide.
AB  - Self-replicating peptide systems hold great promise for a wide range of
      technological applications, as well as to address fundamental questions
      pertaining to the molecular origins of life. The development of self-replicating
      compounds capable of high efficiency, however, has remained elusive. Here we
      disclose a successful strategy whereby modulation of coiled-coil stability
      results in remarkable catalytic efficiency for self-replication. By shortening
      the peptide to the minimum length necessary for coiled-coil formation a highly
      efficient self-replicating system was obtained due to very low background
      reaction rates, bringing the efficiency close to naturally occurring enzymes.

PMID- 12059186
TI  - Chemically induced hairpin formation in DNA monolayers.
AB  - A naphthyridine dimer that binds specifically to G-G mismatches has been used to
      induce hairpin formation in oligonucleotides immobilized onto chemically modified
      gold surfaces. Surface plasmon resonance (SPR) imaging measurements of DNA
      microarrays were used to demonstrate that binding of the naphthyridine dimer to G
      G mismatches within the stem portion of an immobilized 42-mer oligonucleotide
      could be used to induce hairpin formation that prevented hybridization of DNA
      complementary to the loop sequence. In addition, the selectivity of the
      naphthyridine dimer for G-G mismatches was verified through SPR imaging
      measurements of the hybridization adsorption of an 11-mer oligonucleotide to a
      four-component DNA array of zero- and single-base mismatch sequences.

PMID- 12059188
TI  - Activation of arene C[bond]H bonds by a cationic hafnium silyl complex possessing
      an alpha-agostic Si[bond]H interaction.
AB  - The reaction of Cp2Hf(SiMes2H)Me (1) with B(C6F5)3 produces zwitterionic
      Cp2Hf(eta2-SiHMes2)(mu-Me)B(C6F5)3 (2), which is stable for >8 h at -40 degrees C
      in toluene-d8. Spectroscopic data provide evidence for an unusual alpha-agostic
      Si-H interaction in 2. At room temperature, 2 reacts with the C-H bonds of
      aromatic hydrocarbons such as benzene and toluene to produce Cp2Hf(Ph)(mu
      Me)B(C6F5)3 (3), isomers of Cp2Hf(C6H4Me)(mu-Me)B(C6F5)3 (4-6), and
      Cp2Hf(CH2Ph)(mu-Me)B(C6F5)3 (7), respectively. The reaction involving benzene is
      first-order in both 2 and benzene; rate = k[2][C6H6]. Mechanistic data including
      activation parameters (DeltaH = 19(1) kcal/mol; DeltaS = -17(3) eu), a large
      primary isotope effect of 6.9(7), and the experimentally determined rate law are
      consistent with a mechanism involving a concerted transition state for C-H bond
      activation.

PMID- 12059187
TI  - The smallest resonance energy transfer acceptor for tryptophan.
AB  - The utility of diazirine ligands as acceptors in resonance energy transfer (RET)
      distance measurements with tryptophan or tryptophan analogues as donor is
      reported. The principle is demonstrated for a diazirine derivative of d-mannitol,
      2-azi-2-deoxy-d-arabino-hexitol, and single-tryptophan-containing mutants of the
      mannitol transporter, EIImtl, from E. coli. The Forster distance is 10 A for the
      tryptophan-diazirine donor-acceptor couple, allowing the measurement of distances
      up to 17 A. The versatility of tryptophan as an intrinsic spectroscopic probe in
      protein chemistry and the small size of the diazirine group makes this a very
      attractive donor-acceptor couple for accurate RET distance information in protein
      chemistry.

PMID- 12059189
TI  - An indication of magnetic-field-induced superconductivity in a bifunctional
      layered organic conductor, kappa-(BETS)(2)FeBr(4).
AB  - Hybrid systems consisting of the conducting layers of organic donor molecules and
      the magnetic layers of inorganic anions have been focused on as possible
      bifunctional materials, whose conducting properties can be tuned by controlling
      the magnetic state of the anion layers on an application of magnetic field. Here
      we report the magnetoresistance of the antiferromagnetic organic superconductor,
      kappa-(BETS)2FeBr4 [BETS = bis(ethylenedithio)tetraselenafulvalene], consisting
      of the two-dimensional superconducting layers of the BETS semications and the
      insulating layers of the FeBr4- anions. Due to the metamagnetic nature of the
      Fe3+ spin system, characteristic resistivity decrease was observed just below the
      antiferromagnetic superconductor-to-ferromagnetic metal transition at 1.6 T.
      Furthermore, an indication of the onsets of the magnetic-field-induced
      superconductivity was discovered around 12.5 T.

PMID- 12059190
TI  - Ultrafast decay of electronically excited singlet cytosine via a pi,pi* to
      n(O),pi* state switch.
AB  - Singlet fluorescence lifetimes of adenosine, cytidine, guanosine, and thymidine,
      determined by femtosecond pump-probe spectroscopy (Pecourt, J.-M. L.; Peon, J.;
      Kohler, B. J. Am. Chem. Soc. 2000, 122, 9348. Pecourt, J.-M. L.; Peon, J.;
      Kohler, B. J. Am. Chem. Soc. 2001, 123, 10370), show that the excited states
      produced by 263 nm light in these nucleosides decay in the subpicosecond range
      (290-720 fs). Ultrafast radiationless decay to the ground state greatly reduces
      the probability of photochemical damage. In this work we present a theoretical
      study of isolated cytosine, the chromophore of cytidine. The experimental
      lifetime of 720 fs indicates that there must be an ultrafast decay channel for
      this species. We have documented the possible decay channels and approximate
      energetics, using a valence-bond derived analysis to rationalize the structural
      details of the paths. The mechanism favored by our calculations and the
      experimental data involves (1) a two-mode decay coordinate composed of initial
      bond length inversion followed by internal vibrational energy redistribution
      (IVR) to populate a carbon pyramidalization mode, (2) a state switch between the
      pi,pi* and nO,pi* (excitation from oxygen lone pair) excited states, and (3)
      decay to the ground state through a conical intersention. A second decay path
      through the nN,pi* state (excitation from the nitrogen lone pair), with a higher
      barrier, involves out-of-plane bending of the amino substituent.

PMID- 12059192
TI  - FTIR investigation of the intermediates formed in the reaction of nitroprusside
      and thiolates.
AB  - We have studied the outer-sphere reduction of [Fe(CN)5(NO)]2- by several reagents
      including dithionite and have for the first time measured the IR spectra of
      [Fe(CN)5(NO)]3- and [Fe(CN)4(NO)]2- in aqueous media. The spectra of
      [Fe(CN)5(NO)]3- and [Fe(CN)4(NO)]2- are consistent with bent six-coordinate
      {MNO}7 and linear five-coordinate {MNO}7 species, respectively. We have measured
      the UV-visible and IR spectra that evolve after [Fe(CN)5(NO)]2- is reacted with
      thiolate. These spectra permit us to assign the molecular structure of the so
      called "red product" as [Fe(CN)5(eta1-N-RSNO)]3-. We have followed the
      decomposition of the [Fe(CN)5(eta1-N-RSNO)]3- by IR. Importantly, there is a 1:1
      correspondence between the disappearance of the [Fe(CN)5(eta1-N-RSNO)]3- and the
      formation of [Fe(CN)5(NO)]3-. Thus, we conclude under the conditions of this
      study, reduction of [Fe(CN)5(NO)]2- by thiolate takes place via a (dark) inner
      sphere mechanism that yields [Fe(CN)5(NO)]3- via homolytic N-S bond cleavage.

PMID- 12059191
TI  - Tolerance of acyclic residues in the beta-peptide 12-helix: access to diverse
      side-chain arrays for biological applications.
AB  - Oligomeric backbones with well-defined conformational propensities can serve as
      scaffolds for displaying sets of functional groups in specific three-dimensional
      arrangements. beta-Peptides are particularly interesting in this regard because
      several distinct secondary structures can be induced by appropriate choice of
      beta-amino acid substitution pattern.3 The beta-peptide 12-helix (defined by 12
      membered ring C=O(i)- -H-N(i + 3) hydrogen bonds) is of particular interest
      because this helix resembles the alpha-helix. To date 12-helices have been
      observed in beta-peptides comprised exclusively of residues containing a five
      membered ring constraint. Here we show that 12-helical propensity is maintained
      when some cyclic beta-amino acid residues are replaced with more flexible acyclic
      residues. This result is important because use of acyclic residues greatly
      facilitates introduction of diverse side chains at specific sites along the 12
      helix. We demonstrate the utility of this advance in the context of antibiotic
      design.

PMID- 12059193
TI  - Rapid ruthenium-catalyzed synthesis of pyranopyrandiones by reconstructive
      carbonylation of cyclopropenones involving C[bond]C bond cleavage.
AB  - Pyranopyrandiones were prepared by a novel ruthenium-catalyzed carbonylative
      dimerization of cyclopropenones via C-C bond cleavage. For example, treatment of
      dipropylcyclopropenone with a catalytic amount of Ru3(CO)12 and NEt3 in THF under
      15 atm of carbon monoxide at 140 degrees C for 20 h gave a novel functional
      monomer, 3,4,7,8-tetrapropylpyrano[6,5-e]pyran-2,6-dione, in an isolated yield of
      81%. Unsymmetrically substituted pyranopyrandiones were also obtained by
      ruthenium-catalyzed carbonylative coupling of cyclopropenones with alkynes under
      similar reaction conditions.

PMID- 12059194
TI  - Proton coupling to [4Fe-4S](2+/+) and [4Fe-4Se](2+/+) oxidation and reduction in
      a designed protein.
AB  - The coupling of a single proton to [4Fe-4S]2+/+ oxidation/reduction in a de novo
      designed iron-sulfur protein maquette is presented. The reduced state pKared is
      9.3, and the oxidized state pKaox is <6.5. The reduced state pKared shifts to 8.3
      upon incorporation of a [4Fe-4Se]2+/+ cluster, implicating the cluster itself or
      its primary coordination sphere as the proton-coupling site.

PMID- 12059195
TI  - Nonnatural amino acid ligands in heme protein design.
AB  - The de novo design, synthesis, and characterization of a four-alpha-helix bundle
      scaffold containing heme ligated by 4-beta-(pyridyl)-l-alanine (Pal) is
      presented. The protein scaffold is highly helical, stable, and conformationally
      specific in the apo-state. Incorporation of heme using the designed bis-Pal axial
      ligation is shown using UV-visible and EPR spectroscopies. The observed heme
      midpoint reduction potential, +58 mV versus SHE, is 287 mV (6.8 kcal/mol) higher
      than the analogous bis-histidine-ligated heme protein.

PMID- 12059196
TI  - Chiroptical properties of poly(p-phenyleneethynylene) copolymers in thin films:
      large g-values.
AB  - A series of chirally substituted poly (p-phenyleneethynylene) copolymers was
      prepared by alkyne metathesis of mixtures of two different 2,5-dialkyl-1,4
      dipropynylbenzenes. One of the monomers was the chiral bis-2,5-(S)-3,7
      dimethyloctyl-1,4-dipropynylbenzene, and the second one was an achiral dipropynyl
      monomer. If the content of chiral monomer is 25-50 mol %, unusually large
      chiroptical effects, that is, optical dissymmetries, result in absorption (g = 
      0.38) and emission (g = -0.19) of these copolymers. The large dissymmetries can
      be explained by a supramolecular ordering of the PPEs into stranded features that
      are visualized by dark-field transmission electron microscopy. The strands of
      chirally substituted PPEs display a striated structure that suggests that the
      whole feature is a single chirally twisted crystallite.

PMID- 12059197
TI  - Observation of the glycines in elastin using (13)C and (15)N solid-state NMR
      spectroscopy and isotopic labeling.
AB  - We report the solid-state 13C and 15N NMR of insoluble elastin which has been
      synthesized in vitro with isotopically enriched glycine. Most of the glycines
      reside in a domain with good cross-polarization (CP) efficiencies, although
      surprisingly, a portion resides in an environment that is not detectable using
      CP. Our data indicate that much of the 13C population resides in regions of
      significant conformational flexibility. To support these conclusions, we present
      13C and 15N cross-polarization with magic-angle-spinning (CPMAS) data in
      conjunction with "direct-polarization", nonspinning CP, and T1 measurements.

PMID- 12059199
TI  - Helicoid shiftamers.
AB  - We report calculations on the activation barriers for antarafacial [1,7]-hydrogen
      shifts in various helical polyenes containing saturated substructures. Based on
      these calculations, we predict that the barrier for analogous hydrogen shifts in
      the infinite system-a [1,7]-shiftamer-is only approximately 14 kcal/mol if the
      reactant is preorganized in an appropriate helical conformation.

PMID- 12059198
TI  - Aminoacyl-tRNA synthesis by a resin-immobilized ribozyme.
AB  - We report herein a new method for the aminoacylation of tRNA, using a resin
      immobilized ribozyme and the cyanomethyl ester (CME) of an amino acid substrate.
      The oxidized form of the ribozyme was immobilized on a hydrazine resin via
      covalent linkage. We performed aminoacylation of tRNAs using this ribozyme-resin
      to isolate aminoacyl-tRNAs. The column was recycled up to 5 times without
      significant activity loss. Thus, our ribozyme-based aminoacylation system has
      significant potential to be a powerful and practical technique for supplying
      various nonnatural aminoacyl-tRNAs for a highly efficient in vitro translation
      system.

PMID- 12059200
TI  - Sequential actions of cobalt nanoparticles and palladium(II) catalysts: three
      step one-pot synthesis of fenestranes from an enyne and an alkyne diester.
AB  - A three-step one-pot synthesis of fenestranes from a readily available enyne and
      an alkyne diester has been carried out with cobalt nanoparticles and
      palladium(II) as catalysts.

PMID- 12059201
TI  - The first general method for Z-selective olefination of acylsilanes via ynolate
      anions providing multisubstituted alkenes.
AB  - We have developed the first general method for a stereoselective olefination of
      acylsilanes via ynolate anions to produce (Z)-beta-silyl-alpha,beta-unsaturated
      ester, which leads to tri- and tetrasubstituted alkenes.

PMID- 12059202
TI  - Mechanism of the interconversions between C- and N-bound transition metal alpha
      cyanocarbanions.
AB  - The first presentation of the intra- and intermolecular mechanisms of the C-N
      interconversions of transition metal alpha-cyanocarbanions is described. A pair
      of N- and C-bound isomers of isonitrile complex Ru+Cp(NCCH-SO2Ph)(PPh3)(CN-t-Bu)
      (1) and RuCp[CH(CN)SO2Ph](PPh3)(CN-t-Bu) (2) was synthesized for the mechanistic
      studies on the N-to-C isomerizations. Structural characterization by X-ray
      diffractions of 1 and 2 indicated their typical zwitterionic and alpha-metalated
      structures. The kinetic studies on the irreversible isomerization of 1 to 2 in
      benzene-d6 at 333-348 K were carried out using 1H NMR spectroscopy, affording the
      first-order rate constants k1 and the activation parameters DeltaH = 107 +/- 2
      kJ.mol-1 and DeltaS = -22 +/- 5 J.K-1.mol-1. The almost identical values of k1
      were obtained upon similar treatment of 1 with 4 equiv of external ligands such
      as PPh3, CH3CN, and t-BuNC at 333 K, indicating that the N-to-C isomerization
      proceeds in an intramolecular manner without dissociation of a ligand. As a model
      system for the C-to-N isomerization, the irreversible transformation of
      RuCp[CH(CN)SO2Ph](PPh3)2 (3) to Ru+Cp(NCCH-SO2Ph)(PPh3)2 (4) was investigated
      under various reaction conditions. The reaction of 3 at room temperature in THF
      affords the coordination dimers (RRu*,SC*,RRu*,SC*)-{RuCp[CH(CN)SO2Ph](PPh3)}2
      (5) stereoselectively, and its distorted mu2-C,N-bound structure was determined
      by X-ray analysis. The reaction profiles for the isomerization of 3 includes the
      generation- and temperature-dependent decays of dimeric species 5 and its
      diastereomer 6, which strongly suggests that the intra- and intermolecular
      pathways are included in the C-to-N isomerization. The intramolecular process of
      the C-to-N isomerization of 3 has been confirmed by the kinetic studies on the
      isomerization of 3 with excess amount of PPh3 in benzene-d6 at 333-348 K which
      afford the first-order kinetics with the activation parameters of DeltaH = 121 +/
      1 kJ.mol-1 and DeltaS = 42 +/- 4 J.K-1.mol-1. Treatment of 5 with PPh3 in
      boiling benzene gives rise to the quantitative formation of N-bound complex 4.
      The controlled kinetic experiments on the cleavage of 5 with PPh3 have concluded
      that the cleavage of 5 with PPh3 proceeds via simultaneous C-Ru and N-Ru bond
      scissions, indicating the temperature-dependent participation of intermolecular
      process in the C-to-N isomerization of 3.

PMID- 12059203
TI  - Ruthenium(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes with tricarbonyl
      compounds.
AB  - In the presence of catalytic amounts of Cp*Ru(cod)Cl, unsymmetrical 1,6-diynes
      possessing a variety of functional groups reacted with electron-deficient
      tricarbonyl compounds at the ketone C=O double bonds to selectively afford
      dienones via electrocyclic ring opening of the expected alpha-pyrans. The
      intramolecular Michael addition of the cycloadducts having an acetyl and an
      alkylidenemalonate moiety gave bicyclo[3.3.0]octenone derivatives.

PMID- 12059204
TI  - Template-directed assembly of a de novo designed protein.
AB  - Many naturally occurring biomaterials are composed of laminated structures in
      which layers of beta-sheet proteins alternate with layers of inorganic mineral.
      These ordered laminates often have structural and mechanical properties that
      differ significantly from those of nonbiological materials. An important step in
      the construction of novel biomaterials is the creation of composites wherein a de
      novo designed protein assembles into an ordered structure. To achieve this goal,
      we layered a de novo protein onto the surface of highly ordered pyrolytic
      graphite (HOPG). The protein was derived from a combinatorial library of novel
      sequences designed to fold into amphiphilic beta-sheet structures. Atomic force
      microscopy reveals that the protein assembles on the HOPG surface into ordered
      fibers aligned in three orientations at 120 degrees to each other. The symmetry
      and extent of the ordered regions indicate that the hexagonal lattice underlying
      the graphite surface templates assembly of millions of protein molecules into a
      highly ordered structure.

PMID- 12059206
TI  - Molecular structure of single DNA complexes with positively charged dendronized
      polymers.
AB  - Positively charged dendronized polymers with protonated amine groups at the
      periphery and different dendron generations are cylindrically shaped nanoobjects
      whose radii and linear charge densities can be varied systematically. These
      polyelectrolytes have been complexed with DNA and subsequently adsorbed on
      precoated mica substrates. The analysis of scanning force microscopy data
      indicates that DNA wraps around the dendronized polymers. The calculated pitch is
      2.30 +/- 0.27 and 2.16 +/- 0.27 nm for DNA wrapped around dendronized polymers of
      generation two and four, respectively. The complex with the second generation has
      been shown to be negatively charged, which is consistent with the theory of
      spontaneous overcharging of macro-ion complexes, when the electrostatic
      contribution to the free energy dominates over the elastic energy. The complexes
      may be of interest for the development of nonviral gene delivery systems.

PMID- 12059205
TI  - Dynamic docking and electron transfer between Zn-myoglobin and cytochrome b(5).
AB  - We present a broad study of the effect of neutralizing the two negative charges
      of the Mb propionates on the interaction and electron transfer (ET) between horse
      Mb and bovine cyt b(5), through use of Zn-substituted Mb (ZnMb, 1) to study the
      photoinitiated reaction, ((3)ZnP)Mb + Fe(3+)cyt b(5) --> (ZnP)(+)Mb + Fe(2+)cyt
      b(5). The charge neutralization has been carried out both by replacing the Mb
      heme with zinc-deuteroporphyrin dimethylester (ZnMb(dme), 2), which replaces the
      charges by small neutral hydrophobic patches, and also by replacement with the
      newly prepared zinc-deuteroporphyrin diamide (ZnMb(diamide), 3), which converts
      the charged groups to neutral, hydrophilic ones. The effect of propionate
      neutralization on the conformation of the zinc-porphyrin in the Mb heme pocket
      has been studied by multinuclear NMR with an (15)N labeled zinc porphyrin
      derivative (ZnMb((15)N-diamide), 4). The rates of photoinitiated ET between the
      Mb's (1-3) and cyt b(5) have been measured over a range of pH values and ionic
      strengths. Isothermal titration calorimetry (ITC) and NMR methods have been used
      to independently investigate the effect of charge neutralization on Mb/b(5)
      binding. The neutralization of the two heme propionates of ZnMb by formation of
      the heme diester or, for the first time, the diamide increases the second-order
      rate constant of the ET reaction between ZnMb and cyt b(5) by as much as several
      100-fold, depending on pH and ionic strength, while causing negligible changes in
      binding affinity. Brownian dynamic (BD) simulations and ET pathway calculations
      provide insight into the protein docking and ET process. The results support a
      new "dynamic docking" paradigm for protein-protein reactions in which numerous
      weakly bound conformations of the docked complex contribute to the binding of cyt
      b(5) to Mb and Hb, but only a very small subset of these are ET active, and this
      subset does not include the conformations most favorable for binding; the Mb
      surface is a large "target" with a small "bullseye" for the cyt b(5) "arrow".
      This paradigm differs sharply from the more familiar, "simple" docking within a
      single, or narrow range of conformations, where binding strength and ET
      reactivity increase in parallel. Likewise, it is distinct from, although
      complementary to, the well-known picture of conformational control of ET through
      "gating", or a related picture of "conformational coupling". The new model
      describes situations in which tight binding does not correlate with efficient ET
      reactivity, and explains how it is possible to modulate reactivity without
      changing affinity. Such "decoupling" of reactivity from binding clearly is of
      physiological relevance for the reduction of met-Mb in muscle and of met-Hb in a
      red cell, where tight binding of cyt b(5) to the high concentration of ferrous
      Mb/Hb would prevent the cytochrome from finding and reducing the oxidized
      proteins; it likely is of physiological relevance in other situations, as well.

PMID- 12059207
TI  - Phospholipid/protein cones.
AB  - The presence of protein in tubule-forming solutions of the diacetylenic
      phospholipid 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine results in
      the formation of hollow cones rather than the expected hollow cylinders.
      Differential phase-contrast video microscopy reveals that cones grow from
      proteinaceous nodules in a fashion similar to cylindrical tubule growth from
      spherical vesicles. Spatially resolved electron-beam energy-dispersive X-ray
      fluorescence spectroscopy shows the protein to be associated with the cone wall.
      Small-angle X-ray scattering shows that, like the protein-free cylinders, the
      cones are multilamellar with essentially identical interlamellar spacing.

PMID- 12059208
TI  - Recognition of ten base pairs of DNA by head-to-head hairpin dimers.
AB  - Hairpin polyamides coupled head-to head with alkyl linkers of varying lengths
      were synthesized, and their DNA binding properties were determined. The DNA
      binding affinities of six-ring hairpin dimers Im-Im-Py-(R)[Im-Im-Py
      (R)(HNCO(CH))(n)(CO)gamma-Py-Py-Py-beta-Dp](NH)gamma-Im-Py-Py-beta-Dp (1-4)
      (where n = 1-4) for their 10-bp, 11-bp, and 12-bp match sites 5'-TGGCATACCA-3',
      5'-TGGCATTACCA-3', and 5'-TGGCATATACCA-3' were determined by quantitative DNase I
      footprint titrations. The most selective dimer Im-Im-Py-(R)[Im-Im-Py
      (R)(HNCO(CH)(2))(2)(CO)gamma-Py-Py-Py-beta-Dp](NH)gamma-Im-Py-Py-beta-Dp (2)
      binds the 10-bp site match site with an equilibrium association constant of K(a)
      = 7.5 x 10(10) M(-1) and displays 25- and 140-fold selectivity over the 11-bp and
      12-bp match sites, respectively. The affinity toward single base pair mismatched
      sequences is 4- to 8-fold lower if one hairpin module of the dimer is affected,
      but close to 200-fold lower if both hairpin modules face a single mismatch base
      pair. The head-to-head hairpin dimer motif expands the binding site size of DNA
      sequences targetable with polyamides.

PMID- 12059209
TI  - Evaluation of norcarane as a probe for radicals in cytochome p450- and soluble
      methane monooxygenase-catalyzed hydroxylation reactions.
AB  - Norcarane was employed as a mechanistic probe in oxidations catalyzed by hepatic
      cytochome P450 enzymes and by the soluble methane monooxygenase (sMMO) enzyme
      from Methylococcuscapsulatus (Bath). In all cases, the major oxidation products
      (>75%) were endo- and exo-2-norcaranol. Small amounts of 3-norcaranols, 2
      norcaranone, and 3-norcaranone also formed. In addition, the rearrangement
      products (2-cyclohexenyl)methanol and 3-cycloheptenol were detected in the
      reactions, the former possibly arising from a radical intermediate and the latter
      ascribed to a cationic intermediate. The formation of the cation-derived
      rearrangement product is consistent with one or more reaction pathways and is in
      accord with the results of previous probe studies with the same enzymes. The
      appearance of the putative radical-derived rearrangement product is in conflict
      with other mechanistic probe results with the same enzymes. The unique
      implication of a discrete radical intermediate in hydroxylations of norcarane may
      be the consequence of a minor reaction pathway for the enzymes that is not
      manifest in reactions with other probes. Alternatively, it might reflect a
      previously unappreciated reactivity of norcaranyl cationic intermediates, which
      can convert to (2-cyclohexenyl)methanol. We conclude that generalizations
      regarding the intermediacy of radicals in P450 and sMMO enzyme-catalyzed
      hydroxylations based on the norcarane results should be considered hypothetical
      until the origin of the unanticipated results can be determined.

PMID- 12059210
TI  - Metal ion-induced site-selective RNA hydrolysis by use of acridine-bearing
      oligonucleotide as cofactor.
AB  - New types of noncovalent ribozyme-mimics for site-selective RNA scission are
      prepared by combining metal ions with oligonucleotides bearing an acridine.
      Lanthanide(III) ions and various divalent metal ions (Zn(II), Mn(II), Cu(II),
      Ni(II), Co(II), Mg(II), and Ca(II)) are employed without being bound to any
      sequence-recognizing moiety. The modified oligonucleotide forms a heteroduplex
      with the substrate RNA, and selectively activates the phosphodiester linkages in
      front of the acridine. As a result, these linkages are preferentially hydrolyzed
      over the others, even though the metal ions are not fixed anywhere. The scission
      is efficient under physiological conditions, irrespective of the sequence at the
      target site. Site-selective RNA scission is also successful with the combination
      of an oligonucleotide bearing an acridine at its terminus, another unmodified
      oligonucleotide, and the metal ion. In a proposed mechanism, the acridine pushes
      the unpaired ribonucleotide out of the heteroduplex and changes the conformation
      of RNA at the target site for the sequence-selective activation.

PMID- 12059211
TI  - Reduction of ketones and alkyl iodides by SmI(2) and Sm(II)-HMPA complexes. Rate
      and mechanistic studies.
AB  - The effect of HMPA on the electron transfer (ET) rate of samarium diiodide
      reduction reactions in THF was analyzed for a series of ketones (2-butanone,
      methyl acetoacetate, and N,N-dimethylacetoacetamide) and alkyl iodides (1
      iodobutane and 2-iodobutane) with stopped flow spectrophotometric studies.
      Activation parameters for the ET processes were determined by temperature
      dependence studies over a range of 30-50 degrees C. The ET rate constants and the
      activation parameters obtained for the above systems in the presence of different
      equivalents of HMPA were compared to understand the mechanism of action of HMPA
      on various substrates. The results obtained from these studies indicate that
      coordination or chelation is possible in the transition state geometry for
      SmI(2)/ketone systems even in the presence of the sterically demanding ligand
      HMPA. After the addition of 4 equiv of HMPA the ET rate and activation parameters
      for ketone reduction by Sm is unaffected by further HMPA addition while a linear
      dependence of ET rate on the equivalents of HMPA was found in the SmI(2)/alkyl
      iodide system. The results of these studies are consistent with an inner-sphere
      type ET for the reduction of ketones by SmI(2) (and SmI(2)[bond]HMPA complexes)
      and an outer-sphere-type ET for the reduction of alkyl iodides by SmI(2) or
      SmI(2)[bond]HMPA complexes.

PMID- 12059212
TI  - Total synthesis of (-)-rhazinilam: asymmetric C[bond]H bond activation via the
      use of a chiral auxiliary.
AB  - The antitumor agent (-)-rhazinilam was synthesized in three major steps, namely
      the pyrrole synthesis, selective C[bond]H bond activation, and direct macrolactam
      formation. The key step involved asymmetric C[bond]H bond functionalization
      (dehydrogenation) of the diethyl group segment in intermediate 6. This was
      achieved by the attachment of chiral platinum complexes to the proximal nitrogen
      atom. A high degree of selectivity (60-75% ee) was achieved via the use of
      oxazolinyl ketone chiral auxiliaries.

PMID- 12059213
TI  - Chemistry of a novel family of tridentate alkoxy tin(II) clusters.
AB  - The chemical interconversions observed for a novel family of trihydroxymethyl
      ethane (THME-H(3)) ligated Sn(II) compounds have been determined using single
      crystal X-ray and (119)Sn NMR experiments. (mu-THME)(2)Sn(3) (1) was isolated
      from the reaction of 3 equiv of [Sn(NR(2))(2)](2) (R = SiMe(3)) with 4 equiv of
      THME as a unique trinuclear species capped above and below the plane of Sn atoms
      by two THME ligands. Upon reaction with "Sn(NR(2))(2)", compound 1 rearranged to
      yield another novel molecule [(mu-THME)Sn(2)(NR(2))](2) (2). Compound 2 could
      also be formed directly from the stoichiometric mixture of THME-H(3) and
      [Sn(NR(2))(2)](2). Further studies revealed that 1 would also rearrange in the
      presence of Sn(OR)(2) to form [(mu-THME)Sn(2)(mu-OR)](2) [OR = OMe (3), OCH(2)Me
      (4), OCH(2)CH(Me)CH(2)CH(3) (5), OCH(2)CMe(3) (6, ONep), OC(6)H(5) (7, not
      structurally characterized), OC(6)H(4)Me-3 (8), OC(6)H(4)Me-2 (9),
      OC(6)H(3)(Me)(2)-2,6 (10), OC(6)H(3)(CHMe(2))(2)-2,6 (11). Additionally, 3-11
      could by synthesized from the reaction of 2 and the appropriate H-OR. (119)Sn
      solution NMR studies of 2-11, in THF-d(8), indicate that an equilibrium between
      the parent complex and its disassociation products (1 and the free parent Sn
      alkoxy or amide precursor) exists at room temperature. This is a likely reason
      behind the ease of interconversion observed for 1. The generality of this
      exchange was further verified through the reaction of 1 with [Ti(mu
      ONep)(ONep)(3)](2), which led to the isolation of (mu-ONep)(2)Sn(3)(mu
      THME)(2)Ti(ONep)(2) (12). For 12, the solid-state structure was maintained in
      solution with no indication of an equilibrium.

PMID- 12059214
TI  - Synthesis and properties of the first stable germabenzene.
AB  - The first stable germabenzene (1a) bearing an efficient steric protection group,
      2,4,6-tris[bis(trimethylsilyl)methyl]phenyl, was successfully synthesized by the
      reaction of the corresponding chlorogermane (4) with lithium diisopropylamide in
      THF. The molecular structure and aromaticity of 1a were discussed on the basis of
      its NMR, UV-vis, and Raman spectra, X-ray crystallographic analysis, and
      theoretical calculations. All (1)H and (13)C NMR chemical shifts of the
      germabenzene ring of 1a were in good agreement with those calculated. UV-vis and
      Raman spectra of 1a showed patterns similar to those of benzene, suggesting the
      structural similarity between germabenzene and benzene. X-ray crystallographic
      analysis of 1a revealed that the germabenzene ring was almost planar, indicating
      the delocalization of pi-electrons. Theoretical calculations (NICS(1) and
      ASE(isom)) also indicated the ring current effects and aromatic stabilization of
      the germabenzene. While germabenzene 1a reacted as a Ge[bond]C double-bond
      compound (germene) with mesitonitrile oxide and 2,3-dimethyl-1,3-butadiene, 1a
      also reacted as a 1-germabuta-1,3-diene with C[bond]C double- and triple-bond
      compounds. Furthermore, 1a reacted with water and MeOH to give both 1, 2- and 1,
      4-adducts.

PMID- 12059215
TI  - Functionally orthogonal ligand-receptor pairs for the selective regulation of
      gene expression generated by manipulation of charged residues at the ligand
      receptor interface of ER alpha and ER beta.
AB  - The reengineering of protein-small molecule interfaces represents a powerful tool
      of chemical biology. For many applications it is necessary to engineer receptors
      so that they do not interact with their endogenous ligands but are highly
      responsive to designed ligand analogues, which in turn do not interact with
      endogenous proteins. The chemical design strategy used to reengineer protein
      small molecule interfaces is particularly challenging for interfaces involving
      relatively plastic receptor binding sites and therefore presents a unique
      challenge in molecular design. In this study we explore the scope and limitations
      of a new strategy for manipulating polar/charged residues across the ligand
      receptor interface of estradiol (E2) and the estrogen receptor (ER). Carboxylate
      functionalized E2 analogues can activate ER alpha(Glu353-->Ala) and ER
      beta(Glu305-->Ala) with very large selectivites, demonstrating that this design
      strategy is extendable to other members of the steroid hormone receptor family.
      Neutral E2 analogues were found to complement ER alpha(E353A) with similar
      potencies but with generally lower selectivities. This suggests that the high
      selectivity observed with ligand-receptor pairs generated by exchanging charged
      residues across ligand-receptor interfaces is only due in part to their
      complementary shapes and that appropriate introduction of charged functionality
      on the ligand can provide substantial enhancement of selectivity by decreasing
      the engineered ligands affinity for the endogenous receptor. Attempts to modify
      the cationic residues by complementing Arg394-->Ala or Arg394-->Glu were not
      successful.

PMID- 12059217
TI  - Unique dual fluorescence of sterically congested hexaalkyl
      benzenehexacarboxylates: mechanism and application to viscosity probing.
AB  - The static and dynamic fluorescence behavior of a series of hexaalkyl
      benzenehexacarboxylates (R(6)BHC; R = methyl (Me), tert-butyl (tBu), (-)-menthyl
      (Men), (-)-bornyl (Bor), (-)-1-methylheptyl (MHp), neopentyl (neoPn), and 2
      adamantyl (Ad)) was studied by steady-state and time-resolved fluorescence
      spectroscopy. Dual fluorescence from both the partially relaxed metastable Franck
      Condon-like (FC') and the fully relaxed (RX) state was observed for tBu(6)BHC,
      Men(6)BHC, Bor(6)BHC, MHp(6)BHC, neoPn(6)BHC, and Ad(6)BHC, whereas only single
      fluorescence from the RX state was observed for Me(6)BHC. Picosecond time
      resolved fluorescence spectroscopic measurements clearly demonstrated that the
      initially formed Franck-Condon (FC) state sequentially converts to the FC' and
      then to RX state, with the relaxation hindered to such an extent that it shows
      variation with the steric bulk of the R groups. Thus, the fluorescence lifetimes
      (tau's) of FC' and RX are critically dependent on the bulkiness of the R groups,
      varying from 17 to 130 ps and from 0.6 to 1.1 ns, respectively. The relative
      intensity of FC' and RX fluorescence (I(RX)/I(FC)(')) was found to be dependent
      on the excitation wavelength, suggesting that the conformational relaxation from
      the FC' to RX state can compete with the vibrational relaxation of the FC' state.
      The temperature and pressure dependences were studied by steady-state
      fluorescence spectroscopy to give the activation energies of 1-3 kcal/mol for the
      FC'-to-RX relaxation of congested R(6)BHCs, as well as the activation volumes of
      2.0, -0.62, and 7.4 mL/mol for tBu(6)BHC, Men(6)BHC, and Bor(6)BHC at room
      temperature. The fluorescence anisotropy (rho), as a measure of molecular motion,
      was also determined to be in the ranges of 0.03-0.3 for FC' and 0.003-0.01 for
      RX. The much larger rho's for the FC' fluorescence by a factor of 2-100 are
      attributed to the shorter tau's. The I(RX)/I(F' ratio was found to be insensitive
      to solvent polarity, but critically dependent on solvent viscosity, exhibiting an
      excellent linear relationship with the reciprocal viscosity. The potential use of
      these sterically congested R(6)BHCs as microenvironmental viscosity probes is
      proposed.

PMID- 12059216
TI  - Optimization of catalyst enantioselectivity and activity using achiral and meso
      ligands.
AB  - The optimization of asymmetric catalysts for enantioselective synthesis has
      conventionally revolved around the synthesis and screening of enantiopure
      ligands. In contrast, we have optimized an asymmetric reaction by modification of
      a series of achiral ligands. Thus, employing (S)-3,3'-diphenyl BINOL [(S)-Ph(2)
      BINOL] and a series of achiral diimine and diamine activators in the asymmetric
      addition of alkyl groups to benzaldehyde, we have observed enantiomeric excesses
      between 96% (R) and 75% (S) of 1-phenyl-1-propanol. Some of the ligands examined
      have low-energy chiral conformations that can contribute to the chiral
      environment of the catalyst. These include achiral diimine ligands with meso
      backbones that adopt chiral conformations, achiral diimine ligands with backbones
      that become axially chiral on coordination to metal centers, achiral diamine
      ligands that form stereocenters on coordination to metal centers, and achiral
      diamine ligands with pendant groups that have axially chiral conformations.
      Additionally, we have structurally characterized (Ph(2)-BINOLate)Zn(diimine) and
      (Ph(2)-BINOLate)Zn(diamine) complexes and studied their solution behavior.

PMID- 12059218
TI  - Intramolecular dimers: a new strategy to fluorescence quenching in dual-labeled
      oligonucleotide probes.
AB  - Many genomics assays use profluorescent oligonucleotide probes that are
      covalently labeled at the 5' end with a fluorophore and at the 3' end with a
      quencher. It is generally accepted that quenching in such probes without a stem
      structure occurs through Forster resonance energy transfer (FRET or FET) and that
      the fluorophore and quencher should be chosen to maximize their spectral overlap.
      We have studied two dual-labeled probes with two different fluorophores, the same
      sequence and quencher, and with no stem structure: 5'Cy3.5-beta-actin-3'BHQ1 and
      5'FAM-beta-actin-3'BHQ1. Analysis of their absorption spectra, relative
      fluorescence quantum yields, and fluorescence lifetimes shows that static
      quenching occurs in both of these dual-labeled probes and that it is the dominant
      quenching mechanism in the Cy3.5-BHQ1 probe. Absorption spectra are consistent
      with the formation of an excitonic dimer, an intramolecular heterodimer between
      the Cy3.5 fluorophore and the BHQ1 quencher.

PMID- 12059220
TI  - Unusual pathways for metal-assisted C[bond]C and C[bond]P coupling reactions
      using allenylidenerhodium complexes as precursors.
AB  - The rhodium allenylidenes trans-[RhCl[[double bond]C[double bond]C[double
      bond]C(Ph)R](PiPr(3))(2)] [R = Ph (1), p-Tol (2)] react with NaC(5)H(5) to give
      the half-sandwich type complexes [(eta(5)-C(5)H(5))Rh[[double bond]C[double
      bond]C[double bond]C(Ph)R](PiPr(3))] (3, 4). The reaction of 1 with the Grignard
      reagent CH(2)[double bond]CHMgBr affords the eta(3)-pentatrienyl compound
      [Rh(eta(3)-CH(2)CHC[double bond]C[double bond]CPh(2))(PiPr(3))(2)] (6), which in
      the presence of CO rearranges to the eta(1)-pentatrienyl derivative trans
      [Rh[eta(1)-C(CH[double bond]CH(2))[double bond]C[double
      bond]CPh(2)](CO)(PiPr(3))(2)] (7). Treatment of 7 with acetic acid generates the
      vinylallene CH(2)[double bond]CH[bond]CH[double bond]=C=CPh(2) (8). Compounds 1
      and 2 react with HCl to give the five-coordinate allenylrhodium(III) complexes
      [RhCl(2)[CH[double bond]C[double bond]C(Ph)R](PiPr(3))(2)] (10, 11). An unusual
      [C(3) + C(2) + P] coupling process takes place upon treatment of 1 with terminal
      alkynes HC[triple bond]CR', leading to the formation of the eta(3)-allylic
      compounds [RhCl[eta(3)-anti-CH(PiPr(3))C(R')C[double bond]C[double
      bond]CPh(2)](PiPr(3))] [R' = Ph (12), p-Tol (13), SiMe(3) (14)]. From 12 and
      RMgBr the corresponding phenyl and vinyl rhodium(I) derivatives 15 and 16 have
      been obtained. The previously unknown unsaturated ylide iPr(3)PCHC(Ph)[double
      bond]C[double bond]C[double bond]CPh(2) (17) was generated from 12 and CO. A
      [C(3) + P] coupling process occurs on treatment of the rhodium allenylidenes 1,
      2, and trans-[RhCl[[double bond]C[double bond]C[double bond]C(p
      Anis)(2)](PiPr(3))(2)] (20) with either Cl(2) or PhICl(2), affording the ylide
      rhodium(III) complexes [RhCl(3)[C(PiPr(3))C[double bond]C(R)R'](PiPr(3))] (21
      23). The butatrienerhodium(I) compounds trans-[RhCl[eta(2)-H(2)C[double
      bond]C[double bond]C[double bond]C(R)R'](PiPr(3))(2)] (28-31) were prepared from
      1, 20, and trans-[RhCl[[double bond]C[double bond]C[double
      bond]C(Ph)R](PiPr(3))(2)] [R = CF(3) (26), tBu (27)] and diazomethane; with the
      exception of 30 (R = CF(3), R' = Ph), they thermally rearrange to the isomers
      trans-[RhCl[eta(2)-H(2)C[double bond]C[double bond]C[double
      bond]C(R)R'](PiPr(3))(2)] (32, 33, and syn/anti-34). The new 1,1-disubstituted
      butatriene H(2)C[double bond]C[double bond]C[double bond]C(tBu)Ph (35) was
      generated either from 31 or 34 and CO. The iodo derivatives trans-[RhI(eta(2)
      H(2)C[double bond]C[double bond]C[double bond]CR(2))(PiPr(3))(2)] [R = Ph (38), p
      Anis (39)] were obtained by an unusual route from 1 or 20 and CH(3)I in the
      presence of KI. While the hydrogenation of 1 and 26 leads to the allenerhodium(I)
      complexes trans-[RhCl[eta(2)-H(2)C[double bond]C[double bond]C(Ph)R](PiPr(3))(2)]
      (40, 41), the thermolysis of 1 and 20 produces the rhodium(I) hexapentaenes trans
      [RhCl(eta(2)-R(2)C[double bond]C[double bond]C[double bond]C[double bond]C[double
      bond]CR(2))(PiPr(3))(2)] (44, 45) via C-C coupling. The molecular structures of
      3, 7, 12, 21, and 28 have been determined by X-ray crystallography.

PMID- 12059219
TI  - The contrasting kinetics of peroxidation of vitamin E-containing phospholipid
      unilamellar vesicles and human low-density lipoprotein.
AB  - It is well established that alpha-tocopherol, TocH, is an outstanding lipid
      soluble, peroxyl radical trapping antioxidant in homogeneous systems. It is also
      well established that TocH functions as a prooxidant in human low-density
      lipoprotein, LDL, subjected to attack by peroxyl radicals generated in the
      aqueous phase by, for example, thermal decomposition of the azo compound, ABAP.
      This tocopherol-mediated peroxidation, TMP, of LDL involves a three-step chain
      reaction, one step being hydrogen atom abstraction from the LDL lipids by the
      tocopheroxyl radical, Toc*. The occurrence of TMP has been attributed to three
      factors, (i) translocation by TocH of radical character from the aqueous phase
      into LDL lipid, (ii) isolation of the water-insoluble Toc* in the LDL particle in
      which it is formed for times sufficient to permit it to react with the lipid, and
      (iii) the small lipid volume of LDL which ensures that no particle can contain
      more than a single radical for a significant length of time. This consensus view
      of TMP implies that it should occur in any TocH-containing dispersion of small
      lipid particles. However, the present examination of the kinetics of the ABAP
      initiated peroxidation of small unilamellar vesicles, SUVs, made from
      palmitoyllinoleoylphosphatidylcholine and cholesterol with a composition designed
      to mimic the surface coat of LDL, has shown that TocH functions as an antioxidant
      in such systems and that TMP does not occur under conditions where it would have
      occurred if the particles had been LDL. Several possible reasons for the kinetic
      differences between SUVs and LDL have been considered and ruled out by
      experiment. It is concluded that TMP can occur in LDL because these particles
      contain a lipid core in which the Toc* radical "hides" for much of its lifetime
      well away from the peroxyl radicals in the aqueous phase. In contrast, because
      SUVs have no lipid core, the Toc(*) radical is always "exposed" and available to
      aqueous peroxyl radicals with which it reacts rapidly and is destroyed before it
      can abstract a hydrogen atom from the lipid.

PMID- 12059221
TI  - Total synthesis of (-)-bafilomycin A(1).
AB  - A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally
      occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The
      synthesis features the highly stereoselective aldol reaction of methyl ketone 8b
      and aldehyde 60c and a Suzuki cross-coupling reaction of the highly
      functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized
      by a 14-step sequence starting from the readily available beta-alkoxy aldehyde
      14, while the vinylboronic acid component 39 was synthesized by a nine-step
      sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the
      alpha-methoxypropargylation of chiral aldehyde 49 with the alpha
      methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also
      feature diastereoselective double asymmetric crotylboration reactions to set
      several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39
      provided seco ester 40, which following conversion to the seco acid underwent
      smooth macrolactonization to give 41. The success of the macrocyclization
      required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between
      aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high
      diastereoselectivity. Finally, all silicon protecting groups were removed by
      treatment of the penultimate intermediate 65 with TAS-F
      (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the
      total synthesis of (-)-bafilomycin A(1).

PMID- 12059222
TI  - Efficient catalytic enantioselective synthesis of unsaturated amines: preparation
      of small- and medium-ring cyclic amines through mo-catalyzed asymmetric ring
      closing metathesis in the absence of solvent.
AB  - The first catalytic asymmetric ring-closing metathesis method for the synthesis
      of N-containing heterocycles is reported; this is accomplished through Mo
      catalyzed kinetic resolution or desymmetrization of unsaturated amines.
      Importantly, this catalytic asymmetric method delivers medium-ring unsaturated
      amines (including eight-membered rings) in high yield, with exceptional
      enantioselectivity and without the need for solvents. These enantioselective
      reactions can be effected by catalysts prepared in situ from commercially
      available reagents.

PMID- 12059224
TI  - A mechanistic study of the samarium(II)-mediated reduction of aryl nitro
      compounds to the corresponding crylamines. The crystal structures of
      [Sm[N(SiMe(3))(2)](2)(thf)](2)(mu(2)-O) and [(Me(3)Si)(2)N](2)Sm(thf)(mu
      PhNNPh)Sm[N(SiMe(3))(2)](2).
AB  - Treatment of nitrobenzene and other various nitroarenes with 6 equiv of
      samarium(II) under strictly anhydrous conditions allows for the isolation of
      aniline or the corresponding arylamine. Reducing the number of samarium(II)
      equivalents allows for the isolation of intermediate species, e.g., azoarenes or
      hydrazines. Use of Sm[N(SiMe(3))(2)](2), in place of the typically used SmI(2),
      has allowed for the detailed examination of the aqueous and nonaqueous species
      formed in this reduction and has been instrumental in delineation of the stepwise
      reaction mechanism. This is the first time that the reaction intermediates of an
      organic reaction mediated by samarium(II) have been isolated and analyzed by (1)H
      NMR and X-ray crystallography.

PMID- 12059223
TI  - Mechanism of abietadiene synthase catalysis: stereochemistry and stabilization of
      the cryptic pimarenyl carbocation intermediates.
AB  - Abietadiene synthase (AS) catalyzes the complex cyclization-rearrangement of
      (E,E,E)-geranylgeranyl diphosphate (8, GGPP) to a mixture of abietadiene (1a),
      double bond isomers 2a-4a and pimaradienes 5a-7a as a key step in the
      biosynthesis of the abietane resin acid constituents (1b-4b) of conifer
      oleoresin. The reaction proceeds at two active sites by way of the intermediate,
      copalyl diphosphate (9). In the second site, a putative tricyclic pimaradiene or
      pimarenyl(+) carbocation intermediate of undefined C13 stereochemistry and
      annular double bond position is formed. Three 8-oxy-17-nor analogues of 9 (17 and
      19a,b) and three isomeric 15,16-bisnorpimarenyl-N-methylamines (26a-c) were
      synthesized and evaluated as alternative substrates and/or inhibitors for
      recombinant AS from grand fir. The stereospecific cyclization of 8 alpha-hydroxy
      17-nor CPP (19a) to 17-normanoyl oxide (20a) and the higher inhibitory potency of
      the norpimarenylamine 26a (K(i) = 0.1 nM) both suggest pimarenyl intermediates
      having the 13 beta methyl configuration and 8,14-double bond corresponding to
      sandaracopimaradiene (5a). The 2000-fold stimulation of inhibition by 26a in the
      presence of inorganic pyrophosphate indicates an important role for
      carbocation/OPP anion stabilization of the secondary sandaracopimaren-15-yl(+)
      ion. The failure of 8 beta-hydroxy-17-nor CPP (19b) to undergo enzymatic
      cyclization was taken as evidence that 9 is bound with a "coplanar" side chain
      conformation and that the S(N)' cyclization occurs on the 17 alpha face. The
      routing of the sandarcopimara-15-en-8-yl carbocation toward various diterpenes in
      biogenetic schemes is attributed to differing conformations of ring C and/or
      orientations of the C13 vinyl group in the active sites of the corresponding
      diterpene cyclases.

PMID- 12059225
TI  - Measuring polymer surface ordering differences in air and water by sum frequency
      generation vibrational spectroscopy.
AB  - Molecular structures of poly(n-butyl methacrylate) (PBMA) at the PBMA/air and
      PBMA/water interfaces have been studied by sum frequency generation (SFG)
      vibrational spectroscopy. PBMA surfaces in both air and water are dominated by
      the methyl groups of the ester side chains. The average orientation and
      orientation distribution of these methyl groups at the PBMA/air and PBMA/water
      interfaces are different, indicating that surface restructuring occurs when the
      PBMA sample contacts water. Analysis shows that the orientation distribution of
      side chain methyl groups on the PBMA surface is narrower in water than that in
      air, indicating that the PBMA surface can be more ordered in water. To our
      knowledge, this is the first time that quantitative comparisons between molecular
      surface structures of polymers in air and in water have been made. Two
      assumptions on the orientation distribution function, including a Gaussian
      distribution and a formula based on the maximum entropy approach, are used in the
      analysis. It has been found that the orientation angle distribution function
      deduced by the Gaussian distribution and the maximum entropy distribution are
      quite similar, showing that the Gaussian distribution is a good approximation for
      the angle distribution. The effect of experimental error on the deduced
      orientational distribution is also discussed.

PMID- 12059226
TI  - Organocations in zeolite synthesis: fused bicyclo [l.m.0] cations and the
      discovery of zeolite SSZ-48.
AB  - A set of zeolite synthesis experiments is described where lattice substitution is
      varied in the context of the structure of particular structure-directing
      organocations (at times referred to as templates). In this particular series, the
      organocations are constructed as members of a fused bicyclo organonitrogen class
      of compounds, described as having ring construction [l.m.n], where n = 0. We show
      that these compounds can best be achieved from starting cyclic ketones that are
      converted to imines via a Beckman rearrangement reaction. A particular approach
      to the Beckmann reaction works best in our hands. In some instances isomeric
      organocations are made and separated. Often their use in zeolite synthesis led to
      different products. There is a high correlation for the space-filling details of
      the guest organocations and the type of crystalline host lattice developed in the
      synthesis. In one instance involving isomers of a decahydroquinoline derivative,
      a new zeolite, SSZ-48, is discovered and contains only one of the isomers.
      Characterization of the isomers and their use in the zeolites is followed by
      (13)C MAS NMR analyses. Some details of the new zeolite are given and it is shown
      that a reasonable symmetry operation predicting a 14-ring zeolite could be
      generated under similar conditions to SSZ-48 (a 12-ring zeolite).

PMID- 12059227
TI  - Conversion of tricoordinate to hexacoordinate phosphorus. Formation of a
      phosphorane-phosphatrane system.
AB  - Reaction of RPCl(2) with tris(2-hydroxy-3-tert-butyl-5-methylbenzyl)amine (4) led
      to the formation of a tricoordinated phosphonite (1) when R = Ph and to a
      hexacoordinated phosphorane-phosphatrane (2) when R = Et. The X-ray structures
      showed that the unreacted hydroxyl group in 1 oxidatively added to phosphorus in
      2 leading to the formation of three additional bonds, a P[bond]O, a P[bond]H, and
      a P[bond]N linkage. In solution, (31)P measurements assisted by solid-state (31)P
      measurements revealed that each of the compounds existed in both structural
      forms. VT (31)P established equilibria where the solid-state structures
      predominated in each case. This is the first example of a conversion of three
      coordinate to six-coordinate phosphorus on going from the solid to the solution
      state and the existence of these two disparate geometries in equilibrium with one
      another in solution. In the absence of steric protection with the use of an
      analogous amine (5) without tert-butyl groups, a hydrolysis reaction occurred
      with PhPCl(2). X-ray analysis revealed an anionic phenylphosphinate structure (3)
      hydrogen bonded in a cage-like arrangement with the protonated amine. Similar
      hydrolysis reactions take place with 1 and 2 but much more slowly.

PMID- 12059228
TI  - TpPtMe(H)(2): why is there H/D scrambling of the methyl group but not methane
      loss?
AB  - The reactivity of TpPtMe(H)(2) (Tp = hydrido-tris(pyrazolyl)borate) was
      investigated. This complex is remarkably resistant to methane loss; heating it in
      methanol at 55 degrees C does not lead to either methane or hydrogen loss. When
      CD(3)OD is used, reversible H/D scrambling of the hydrides and the methyl
      hydrogens occurs. This reactivity was investigated by density functional theory
      (DFT) methods at the mPW1k/LANL2DZ+P//mPW1k/LANL2DZ level. It was found that
      methane loss cannot occur due to the rigidity of the Tp ligand, which does not
      allow the trans geometry which would be required for the product of methane
      elimination, TpPtH. The resulting complex is very high in energy, and therefore
      the loss of methane is unfavorable. On the other hand, H/D scrambling of the
      methyl ligand is relatively facile. It proceeds through an eta(2-CH)-CH(4)
      complex, even though methane loss is not observed. The model system,
      [(NH(3))(3)PtMe(H)(2)](+) was examined to verify that the cause of the
      observations is the rigidity of the Tp system. The reaction was investigated at a
      number of levels of DFT. It was concluded that investigations of similar sized
      systems should be examined at the above level of theory or the mPW1k/SDB-cc
      pVDZ//mPW1k/SDD level for improved accuracy of the energetic calculations.

PMID- 12059229
TI  - Biosynthesis of nodulisporic acid A: precursor studies.
AB  - Nodulisporic acid A (NAA) is an indole-diterpene natural product produced by an
      indeterminate species of the endophytic fungus Nodulisporium. NAA (Figure 1) is
      structurally related to the paspaline class of fungal metabolites. The
      biosynthetic origin proposed for these alkaloids involves the acetate/mevalonic
      acid pathway leading to geranylgeranyl pyrophosphate (GGPP). GGPP is then
      proposed to condense with tryptophan to form the basic indole-diterpene core. A
      washed cell procedure was devised to incorporate labeled precursors into NAA by a
      mutant Nodulisporium culture designated MF6244. Incorporation of 2-(13)C-acetate
      and 2-(13)C-mevalonolactone into NAA was found to occur in the classical
      mevalonic acid pattern. In addition to the four mevalonic acid units that form
      the eastern side of the molecule, three additional isoprenylations occur to form
      the western and southern regions of NAA. Contrary to published reports on related
      compounds, incubations of Nodulisporium MF6244 with (14)C- and (13)C-tryptophan
      showed no incorporation of label into NAA. However, high levels of incorporation
      into NAA were obtained with known tryptophan precursors (14)C-, (13)C-, and (15)N
      anthranilic acid and (14)C- and (13)C-ribose. A novel pathway for the
      biosynthesis of NAA is presented.

PMID- 12059231
TI  - Sorting fluorescent nanocrystals with DNA.
AB  - Semiconductor nanocrystals with narrow and tunable fluorescence are covalently
      linked to oligonucleotides. These biocompounds retain the properties of both
      nanocrystals and DNA. Therefore, different sequences of DNA can be coded with
      nanocrystals and still preserve their ability to hybridize to their complements.
      We report the case where four different sequences of DNA are linked to four
      nanocrystal samples having different colors of emission in the range of 530-640
      nm. When the DNA-nanocrystal conjugates are mixed together, it is possible to
      sort each type of nanoparticle by using hybridization on a defined micrometer
      size surface containing the complementary oligonucleotide. Detection of sorting
      requires only a single excitation source and an epifluorescence microscope. The
      possibility of directing fluorescent nanocrystals toward specific biological
      targets and detecting them, combined with their superior photostability compared
      to organic dyes, opens the way to improved biolabeling experiments, such as gene
      mapping on a nanometer scale or multicolor microarray analysis.

PMID- 12059230
TI  - Total syntheses of the phytotoxic lactones herbarumin I and II and a synthesis
      based solution of the pinolidoxin puzzle.
AB  - A concise approach to a family of potent herbicidal 10-membered lactones is
      described on the basis of ring-closing metathesis (RCM) as the key step for the
      formation of the medium-sized ring. This includes the first total syntheses of
      herbarumin I (1) and II (2) as well as the synthesis of several possible
      macrolides of the pinolidoxin series. A comparison of their spectral and
      analytical data with those of the natural product allowed us to establish the
      stereostructure of pinolidoxin, a potent inhibitor of induced phenylalanine
      ammonia lyase (PAL) activity, as shown in 46. This finding, however, makes clear
      that a previous study dealing with the relative and absolute stereochemistry of
      this phytotoxic agent cannot be correct. An important aspect from the preparative
      point of view is the fact that the stereochemical outcome of the RCM reaction can
      be controlled by the choice of the catalyst. Thus, use of the ruthenium
      indenylidene complex 16 always leads to the corresponding (E)-alkenes, whereas
      the second generation catalyst 17 bearing an N-heterocyclic carbene ligand
      affords the isomeric (Z)-olefin with good selectivity. This course is deemed to
      reflect kinetic versus thermodynamic control of the cyclization reaction and
      therefore has potentially broader ramifications for the synthesis of medium-sized
      rings in general. A further noteworthy design feature is the fact that D-ribose
      is used as a convenient starting material for the preparation of both enantiomers
      of the key building block 14 by means of a "head-to-tail" interconversion
      strategy.

PMID- 12059232
TI  - Solution and solid-state structural studies of epoxide adducts of cadmium
      phenoxides. Chemistry relevant to epoxide activation for ring-opening reactions.
AB  - The reaction of Cd[N(SiMe(3))(2)](2) with 2 equiv of the corresponding phenol in
      toluene has led to the isolation of [Cd(O-2,6-R(2)C(6)H(3))(2)](2) derivatives,
      where R represents the sterically bulky (t)Bu and Ph substituents. The dimeric
      nature of these complexes in the solid state has been established via X-ray
      crystallography, i.e., trigonal geometry around cadmium is observed in 1 (R =
      (t)Bu) where the two cadmium centers are bridged by two phenoxides with each
      metal containing a terminal phenoxide. Complex 2 (R = Ph) contains an additional
      interaction of the metal centers with carbon atoms of the aromatic substituents
      on the phenoxide ligands. These dimeric structures are maintained in weakly
      coordinating solvents as revealed by (113)Cd NMR in d(2)-methylene chloride,
      which displays (111)Cd-(113)Cd coupling. Nevertheless, because of the excessive
      steric requirements of these phenoxide ligands, these dimers are easily disrupted
      in solution by weak donor ligands such as epoxides. Three bisepoxide adducts have
      been isolated as crystalline solids and characterized by X-ray crystallography.
      As previously observed in other Cd(O-2,6-(t)Bu(2)C(6)H(3))(2) x L(2) complexes,
      these epoxide adducts adopt a crystallographically imposed square-planar geometry
      about the cadmium centers, with the exception of the exo-2,3-epoxynorbornane
      derivative, which displays a distorted tetrahedral geometry. Temperature
      dependent (113)Cd NMR studies have established that there is little difference in
      the binding abilities of these epoxides with either complex 1 or complex 2.
      Importantly, it is concluded from these studies that the lack of reactivity of
      alpha-pinene oxide and exo-2,3-epoxynorbornane toward copolymerization reactions
      with carbon dioxide, in the presence of zinc bisphenoxide catalysts, is not due
      to differences in epoxide metal binding. This is further affirmed by the
      isolation and crystallographic characterization of the very stable Zn(O-2,6
      (t)Bu(2)C(6)H(3))(2) x (exo-2,3-epoxynorbornane)(2) derivative.

PMID- 12059233
TI  - Hydrogen activation on Mo-based sulfide catalysts, a periodic DFT study.
AB  - Hydrogen adsorption on Mo[bond]S, Co[bond]Mo[bond]S, and Ni[bond]Mo[bond]S (10 1
      macro 0) surfaces has been modeled by means of periodic DFT calculations taking
      into account the gaseous surrounding of these catalysts in working conditions. On
      the stable Mo[bond]S surface, only six-fold coordinated Mo cations are present,
      whereas substitution by Co or Ni leads to the creation of stable coordinatively
      unsaturated sites. On the stable MoS(2) surface, hydrogen dissociation is always
      endothermic and presents a high activation barrier. On Co[bond]Mo[bond]S
      surfaces, the ability to dissociate H(2) depends on the nature of the metal atom
      and the sulfur coordination environment. As an adsorption center, Co strongly
      favors molecular hydrogen activation as compared to the Mo atoms. Co also
      increases the ability of its sulfur atom ligands to bind hydrogen. Investigation
      of surface acidity using ammonia as a probe molecule confirms the crucial role of
      sulfur basicity on hydrogen activation on these surfaces. As a result,
      Co[bond]Mo[bond]S surfaces present Co[bond]S sites for which the dissociation of
      hydrogen is exothermic and weakly activated. On Ni[bond]Mo[bond]S surfaces,
      Ni[bond]S pairs are not stable and do not provide for an efficient way for
      hydrogen activation. These theoretical results are in good agreement with recent
      experimental studies of H(2)[bond]D(2) exchange reactions.

PMID- 12059234
TI  - Dynamics and extent of ligand exchange depend on electronic charge of metal
      nanoparticles.
AB  - Both the rate and extent of ligand place exchange reactions between the
      hexanethiolate monolayer of Au(140) monolayer protected clusters (C6 MPCs) and
      dissolved 6-mercapto-1-hexanol thiol (HOC6SH) increase with increasing positive
      electronic charge on the Au cluster core. The rate constant of the ligand place
      exchange, taken at the early stage of the exchange, is increased by ca. 2-fold
      for reaction of +3 charged Au(140) cores as compared to neutral ones. The
      initially exchanged ligands are thought to reside mainly on edge and vertex sites
      of the Au(140) core, where the lability of the slightly more ionic Au[bond]S
      bonds there becomes further enhanced by removing electrons from the core. The
      reactions slow markedly after 35-50% of the original ligands have been replaced,
      continuing at a much slower pace for some time to reach an apparent reaction
      equilibrium. On +2 charged Au(140) cores, 85% of the C6 ligands have been
      exchanged with HOC(6)H(12)SH after 20 h. The slower phase of the reaction
      includes exchange of thiolate ligands on terrace lattice sites most of which-
      owing to the small sizes of the nanoparticle's Au(111) faces--are no more than
      one Au atom row removed from the nanoparticle edge sites. This slower exchange,
      the extent of which is also enhanced by positively charging the core, occurs
      either by intramolecular place exchange with edge sites that subsequently place
      exchange with solution thiol or by direct place-exchange with solution thiol.
      Acid-base studies show that thiolate is more reactive in place exchange reactions
      than the corresponding thiol.

PMID- 12059235
TI  - High-resolution solid-state (13)C NMR studies of chemisorbed organometallics.
      Chemisorptive formation of cation-like and alkylidene organotantalum complexes on
      high surface area inorganic oxides.
AB  - (13)C CPMAS NMR spectroscopy has been employed to investigate the surface
      chemistry of the organotantalum hydrocarbyl/alkylidene complexes,
      Cp'Ta((13)CH(3))(4) (1*), Cp(2)Ta((13)CH(3))(3) (2*),
      Cp(2)Ta((13)CH(2))((13)CH(3)) (3*), and Ta((13)CH(t)Bu)((13)CH(2)(t)Bu)(3) (4*)
      [Cp' = eta(5)-(CH(3))(5)C(5), Cp = eta(5)-C(5)H(5)] supported on partially
      dehydroxylated silica (PDS), dehydroxylated silica (DS), or dehydroxylated gamma
      alumina (DA). Mono-Cp tantalum hydrocarbyl 1* undergoes chemisorption to form
      Cp'Ta((13)CH(3))(3)O-Si mu-oxo species on silica, and "cation-like"
      Cp'Ta((13)CH(3))(3)(+) and Cp'Ta((13)CH(3))(3)O-Al mu-oxo species on DA, via
      pathways analogous to those established for organo-group 4 and actinide
      complexes. When supported on DA, bis-Cp tantalum hydrocarbyl 2* follows the same
      chemisorption mode as 1*. However, when 2* is chemisorbed on PDS and DS, a
      "cation-like" Cp(2)Ta((13)CH(3))(2)(+) species is the major adsorbate product. On
      PDS, bis-Cp tantalum alkylidene complex 3* is converted predominantly to a stable
      "cation-like" Cp(2)Ta((13)CH(3))(2)(+) species, presumably via electrophilic
      addition of a proton from the PDS surface. In contrast to 3*, Ta alkylidene
      complex 4* forms predominantly a Ta((13)CH(t)Bu)((13)CH(2)(t)Bu)(2)O-Si, mu-oxo
      alkylidene species on PDS.

PMID- 12059236
TI  - Extending the coordination chemistry of molecular P(4)S(3): the polymeric
      Ag(P(4)S(3))(+) and Ag(P(4)S(3))(2)(+) cations.
AB  - Upon reacting P(4)S(3) with AgAl(hfip)(4) and AgAl(pftb)(4) [hfip =
      OC(H)(CF(3))(2); pftb = OC(CF(3))(3)], the compounds Ag(P(4)S(3))Al(hfip)(4) 1
      and Ag(P(4)S(3))(2)(+)[Al(pftb)(4)](-) 2 formed in CS(2) (1) or CS(2)/CH(2)Cl(2)
      (2) solution. Compounds 1 and 2 were characterized by single-crystal X-ray
      structure determinations, Raman and solution NMR spectroscopy, and elemental
      analyses. One-dimensional chains of [Ag(P(4)S(3))(x)](infinity) (x = 1, 1; x = 2,
      2) formed in the solid state with P(4)S(3) ligands that bridge through a 1,3-P,S,
      a 2,4-P,S, or a 3,4-P,P eta(1) coordination to the silver ions. Compound 2 with
      the least basic anion contains the first homoleptic metal(P(4)S(3)) complex.
      Compounds 1 and 2 also include the long sought sulfur coordination of P(4)S(3).
      Raman spectra of 1 and 2 were assigned on the basis of DFT calculations of
      related species. The influence of the silver coordination on the geometry of the
      P(4)S(3) cage is discussed, additionally aided by DFT calculations. Consequences
      for the frequently observed degradation of the cage are suggested. An
      experimental silver ion affinity scale based on the solid-state structures of
      several weak Lewis acid base adducts of type (L)AgAl(hfip)(4) is given. The
      affinity of the ligand L to the silver ion increases according to P(4) <
      CH(2)Cl(2) < P(4)S(3) < S(8) < 1,2-C(2)H(4)Cl(2) < toluene.

PMID- 12059237
TI  - Impact of defects on the surface chemistry of ZnO(0001 macro)-O.
AB  - Scanning tunneling microscopy and core level photoelectron spectroscopy
      measurements have been used to investigate the morphology of ZnO(0001 macro)-O,
      and its reactivity with carbon monoxide and carbon dioxide, as a function of
      surface preparation. Real space images of the surface indicate that increasing
      the substrate anneal temperature during preparation significantly reduces the
      surface step density. Surface defect concentration is also monitored by employing
      formic acid as a chemical probe, which is shown to adsorb dissociatively (HCOOH -
      > [HCOO](-) + H(+)) only on zinc cations at step edges. Carbon 1s X-ray
      photoelectron spectra show that carbon monoxide and carbon dioxide both react to
      form surface carbonate species. Spectra, recorded both as a function of surface
      preparation and following coadsorption, demonstrate that the carbonate formed
      from either reactant molecule is located at oxygen vacancies at step edges,
      evidencing the significant role that defects can play in the surface chemistry of
      ZnO(0001 macro)-O.

PMID- 12059238
TI  - Long-lived charge-separation by retarding reverse flow of charge-balancing cation
      and zeolite-encapsulated Ru(bpy)(3)(2+) as photosensitized electron pump from
      zeolite framework to externally placed viologen.
AB  - K(+)-exchanged, Ru(bpy)(3)(2+)-encapsulating zeolite-Y [K(+)-Ru(bpy)(3)(2+)Y] and
      N-[3-(dicyclohexylmethyl)oxypropyl-N'-methyl-4,4'-bipyridinium [DCH-MV(2+)] were
      prepared, and visible light-induced electron transfer from the zeolite
      encapsulated Ru(II) complex to the size-excluded viologen was studied in
      acetonitrile. Addition of a series of crown ethers (CEs) into the heterogeneous
      solution leads to over a 10-fold increase in the yield of DCH-MV(*)(+), where the
      yield linearly increases as the formation constant of CE with K(+)
      [K(f)(K(+))(CE)] increases. The following two sequential events are attributed to
      be responsible for the above novel phenomenon. First, K(+) ions are liberated
      from the zeolite to solution during interfacial electron transfer from the
      photoexcited Ru(II) complexes to DCH-MV(2+). Second, the liberated K(+) ions form
      strong host-guest complexes with the added CE molecules, which leads to
      retardation of the reverse flow of the cations, hence the charge-balancing
      electrons, from the solution to the zeolite. Surprisingly, the yield of DCH
      MV(*)(+) reaches more than approximately 50 times the amount of Ru(bpy)(3)(2+)
      situated in the outermost supercages, despite the absence of electron relay in
      the zeolite. This is attributed to photosensitized electron pumping from the
      zeolite framework to viologen by the outermost Ru(bpy)(3)(2+) ions. In support of
      the above conclusion, Ru(bpy)(3)(3+) does not accumulate in the zeolite host
      while DCH-MV(*)(+) accumulates in the supernatant solution. Consistent with the
      above, the independently prepared hexafluorophosphate salt of Ru(bpy)(3)(3+) is
      reduced to Ru(bpy)(3)(2+) in acetonitrile upon contact with Ru(bpy)(3)(2+)-free
      M(+)Y (M(+) = Li(+), Na(+), K(+), Rb(+), and Cs(+)), where the yield increases as
      the donor strength of the framework oxygen increases. Although small, thermal
      electron transfer also takes place from the zeolite framework to DCH-MV(2+),
      where the yield increases upon increasing the donor strength of the framework,
      concentration of DCH-MV(2+), temperature, and K(f)(K(+))(CE) (when K(+)Y is the
      zeolite host). The photoyield is always higher than the thermal yield by 4-30
      times, confirming that the zeolite-encapsulated Ru(bpy)(3)(2+) serves as the
      photosensitized electron pump.

PMID- 12059239
TI  - Epitaxial growth and photochemical annealing of graded CdS/ZnS shells on
      colloidal CdSe nanorods.
AB  - We report the preparation and structural characterization of core/shell
      CdSe/CdS/ZnS nanorods. A graded shell of larger band gap is grown around CdSe
      rods using trioctylphosphine oxide as a surfactant. Interfacial segregation is
      used to preferentially deposit CdS near the core, providing relaxation of the
      strain at the core/shell interface. The reported synthesis allows for variation
      of the shell thickness between one and six monolayers, on core nanorods ranging
      from aspect ratios of 2:1 to 10:1. After an irreversible photochemical annealing
      process, the core/shell nanorods have increased quantum efficiencies and are
      stable in air under visible or UV excitation. In addition to their robust optical
      properties, these samples provide an opportunity for the study of the evolution
      of epitaxial strain as the shape of the core varies from nearly spherical to
      nearly cylindrical.

PMID- 12059240
TI  - Heme charge-transfer band III is vibronically coupled to the Soret band.
AB  - A complete resonance Raman excitation profile of the heme charge-transfer band
      known as band III is presented. The data obtained throughout the near-infrared
      region show preresonance with the Q-band, but the data also clearly show the
      enhancement of a number of modes in the spectral region of band III. Only
      nontotally symmetric modes are observed to have resonance enhancement in the band
      III region. The observed resonance enhancements in modes of B(1g) symmetry are
      compared with the enhancements of those same modes in the excitation profiles of
      the Q-band of deoxy myoglobin, also presented here for this first time. The Q
      band data agree well with the theory of vibronic coupling in metalloporphyrins
      (Shelnutt, J. A. J. Chem. Phys. 1981, 74, 6644-6657). The strong vibronic
      coupling of the Q-band of the deoxy form of hemes is discussed in terms of the
      enhancement of modes with both B(1g) and A(2g) symmetry. The comparison between
      the Q-band and band III reveals that, consistent with the theory, only modes of
      B(1g) symmetry are enhanced in the vicinity of band III. These results show that
      band III is vibronically coupled to the Soret band. The coupling of band III to
      modes with strong rhombic distortion of the heme macrocycle calls into question
      the hypothesis that the axial iron out-of-plane displacement is primarily
      responsible for the structure-dynamics correlations observed in myoglobin.

PMID- 12059241
TI  - Residue-specific real-time NMR diffusion experiments define the association
      states of proteins during folding.
AB  - Characterizing the association states of proteins during folding is critical for
      understanding the nature of protein-folding intermediates and protein-folding
      pathways, protein aggregation, and disease-related aggregation. To study the
      association states of unfolded, folded, and intermediate species during protein
      folding, we have introduced a novel residue-specific real-time NMR diffusion
      experiment. This experiment, a combination of NMR real-time folding experiments
      and 3D heteronuclear pulsed field gradient NMR diffusion experiments (LED-HSQC),
      measures hydrodynamic properties, or molecular sizes, of kinetic species directly
      during the folding process. Application of the residue-specific real-time NMR
      diffusion experiments to characterize the folding of the collagen triple helix
      motif shows that this experiment can be used to determine the association states
      of unfolded, folded, and kinetic intermediates with transient lifetimes
      simultaneously. The ratio of the apparent translational diffusion coefficients of
      the unfolded to the folded form of the triple helix is 0.59, which correlates
      very well with a theoretical ratio for monomer to linear trimer. The apparent
      diffusion coefficients of the kinetic intermediates formed during triple helix
      folding indicate the formation of trimer-like associates which is consistent with
      previously published kinetic and relaxation data. The residue-specific time
      dependence of apparent diffusion coefficients of monomer and trimer peaks also
      illustrates the ability to use diffusion data to probe the directionality of
      triple helix formation. NMR diffusion experiments provide a new strategy for the
      investigation of protein-folding mechanisms, both to understand the role of
      kinetic intermediates and to determine the time-dependent aggregation processes
      in human diseases.

PMID- 12059242
TI  - Magnitudes and chemical consequences of R(3)N(+)-C-H...O[double bond]C hydrogen
      bonding.
AB  - The magnitude of the stabilizing interaction between an aliphatic C[bond]H bond
      attached to an ammonium nitrogen and a carbonyl oxygen was evaluated by ab initio
      calculations at the MP2/6-311++G** level of theory. Attractive R(3)N(+)-C
      H...O[double bond]C interactions play an important role in supramolecular
      recognition and various types of stereoselective catalysis. Our calculations show
      that R(3)N(+)-C-H...O[double bond]C is the strongest hydrogen bond of the C-H...O
      type known to date. Such hydrogen bonds remain as stabilizing interactions even
      in water for amide acceptors.

PMID- 12059243
TI  - Selective formation of cumulative double bonds (C[double bond]C[double bond]N) in
      the attachment of multifunctional molecules on Si(111)-7 x 7.
AB  - The cumulative double bond (C[double bond]C[double bond]N), an important
      intermediate in synthetic organic chemistry, was successfully prepared via the
      selective attachment of acrylonitrile to Si(111)-7 x 7. The covalent binding of
      acrylonitrile on Si(111)-7 x 7 was studied using high-resolution electron energy
      loss spectroscopy (HREELS), X-ray photoelectron spectroscopy (XPS), ultraviolet
      photoelectron spectroscopy (UPS), scanning tunneling microscopy (STM) and DFT
      calculations. The observation of the characteristic vibrational modes and
      electronic structures of the C[double bond]C[double bond]N group in the surface
      species demonstrates the [4 + 2]-like cycloaddition occurring between the
      terminal C and N atoms of acrylonitrile and the neighboring adatom-rest atom
      pair, consistent with the prediction of DFT calculations. STM studies further
      show the preferential binding of acrylonitrile on the center adatom sites of
      faulted halves of Si(111)-7 x 7 unit cells.

PMID- 12059244
TI  - Mechanism of C[bond]H bond activation/C[bond]C bond formation reaction between
      diazo compound and alkane catalyzed by dirhodium tetracarboxylate.
AB  - The B3LYP density functional studies on the dirhodium tetracarboxylate-catalyzed
      C-H bond activation/C-C bond formation reaction of a diazo compound with an
      alkane revealed the energetics and the geometry of important intermediates and
      transition states in the catalytic cycle. The reaction is initiated by
      complexation between the rhodium catalyst and the diazo compound. Driven by the
      back-donation from the Rh 4d(xz) orbital to the C[bond]N sigma*-orbital, nitrogen
      extrusion takes place to afford a rhodium[bond]carbene complex. The carbene
      carbon of the complex is strongly electrophilic because of its vacant 2p orbital.
      The C[bond]H activation/C[bond]C formation proceeds in a single step through a
      three-centered hydride transfer-like transition state with a small activation
      energy. Only one of the two rhodium atoms works as a carbene binding site
      throughout the reaction, and the other rhodium atom assists the C[bond]H
      insertion reaction. The second Rh atom acts as a mobile ligand for the first one
      to enhance the electrophilicity of the carbene moiety and to facilitate the
      cleavage of the rhodium[bond]carbon bond. The calculations reproduce experimental
      data including the activation enthalpy of the nitrogen extrusion, the kinetic
      isotope effect of the C[bond]H insertion, and the reactivity order of the
      C[bond]H bond.

PMID- 12059245
TI  - A first-principles study of methanol decomposition on Pt(111).
AB  - A periodic, self-consistent, Density Functional Theory study of methanol
      decomposition on Pt(111) is presented. The thermochemistry and activation energy
      barriers for all the elementary steps, starting with O[bond]H scission and
      proceeding via sequential hydrogen abstraction from the resulting methoxy
      intermediate, are presented here. The minimum energy path is represented by a one
      dimensional potential energy surface connecting methanol with its final
      decomposition products, CO and hydrogen gas. It is found that the rate-limiting
      step for this decomposition pathway is the abstraction of hydroxyl hydrogen from
      methanol. CO is clearly identified as a strong thermodynamic sink in the reaction
      pathway while the methoxy, formaldehyde, and formyl intermediates are found to
      have low barriers to decomposition, leading to very short lifetimes for these
      intermediates. Stable intermediates and transition states are found to obey gas
      phase coordination and bond order rules on the Pt(111) surface.

PMID- 12059246
TI  - Molecular-scale tribology of amorphous carbon coatings: effects of film
      thickness, adhesion, and long-range interactions.
AB  - Classical molecular dynamics simulations have been conducted to investigate the
      atomic-scale friction and wear when hydrogen-terminated diamond (111)
      counterfaces are in sliding contact with diamond (111) surfaces coated with
      amorphous, hydrogen-free carbon films. Two films, with approximately the same
      ratio of sp(3)-to-sp(2) carbon, but different thicknesses, have been examined.
      Both systems give a similar average friction in the load range examined. Above a
      critical load, a series of tribochemical reactions occur resulting in a
      significant restructuring of the film. This restructuring is analogous to the
      "run-in" observed in macroscopic friction experiments and reduces the friction.
      The contribution of adhesion between the probe (counterface) and the sample to
      friction was examined by varying the saturation of the counterface. Decreasing
      the degree of counterface saturation, by reducing the hydrogen termination,
      increases the friction. Finally, the contribution of long-range interactions to
      friction was examined by using two potential energy functions that differ only in
      their long-range forces to examine friction in the same system.

PMID- 12059247
TI  - IR and theoretical studies of monocarbonyl Ni complexes formed by adsorption of
      CO at low pressure on silica-supported Ni(II) ions.
AB  - This work reports on the reactivity of coordination vacancies of Ni(II) ions
      grafted onto the tridentate silica support (Ni(II)(3c) ions) with respect to CO
      used as a probe molecule. The adsorption of CO at 77 K in the 0.3 to 3.5 Pa CO
      pressure range is studied by FTIR on two samples differing in the dispersion of
      nickel. Quantum chemical calculations by the DFT method are performed to
      investigate, using a cluster approach, the binding of Ni to silica and, after CO
      adsorption, the geometry of the resulting carbonyl Ni complexes. Silica is
      modeled by using clusters composed of three types of monodentate ligands, SiO(-),
      SiOSi and/or SiOH, found on the surface of silica. This work is devoted to the
      monocarbonyl complexes. Whatever the sample, only one type of monocarbonyl is
      formed from Ni(II)(3c) ions. It is shown that the charge of the silica cluster is
      the major parameter influencing the CO IR frequency whereas the nature and the
      size of the silica cluster do not affect the CO bond length, confirming that
      local electrostatic interactions predominate. Only the 1- charged silica cluster
      Si(5)O(3)(-), composed of SiO(-), 2SiOSi fragments, respectively, reproduces the
      Ni[bond]O distances derived from EXAFS for the Ni(II)(3c) grafted site and gives
      CO frequencies in good agreement with the experimental values. It is shown that
      CO is stabilized by a magnetic transition from the (3)Ni(2+) triplet to the
      (1)Ni(2+) singlet state occurring upon adsorption.

PMID- 12059248
TI  - Theoretical study of benzonitrile clusters in the gas phase and their adsorption
      onto a Au(111) surface.
AB  - We made theoretical calculations for a benzonitrile molecule and its clusters in
      the gas phase and as adsorbed on the Au(111) surface, to explain the observation
      by scanning tunneling microscope, that is, the trimer formation of cyanophenyl
      porphyrins adsorbed onto the Au(111) surface. With regard to the gas-phase
      species, ab initio calculations showed that (1) the benzonitrile dimer has a
      single stable structure that is planar and antiparallel; (2) the trimer has two
      isoenergetic stable structures, that is, a planar and cyclic structure and an
      antiparallel and nonplanar one; (3) the clusters are more stable, at low
      temperatures, than the monomer. For the adsorbed species, we made quantum
      mechanical/molecular mechanical calculations in which the interaction between the
      adsorbates and the surface is evaluated in a molecular-mechanical way by using
      analytical potential functions and an image charge model. Because the stable
      structures were found to be similar to those in the gas phase, the cluster
      formation of adsorbed cyanophenyl porphyrins was attributed to the interaction
      between cyanophenyl groups, which is barely affected by adsorbate-surface
      interaction. It was also found that the adsorbed cyclic benzonitrile trimer is
      more stable than the monomer and the dimer because the relative stability is
      dependent on enthalpy alone. We therefore concluded that the preferential
      formation of trimers by the adsorbed cyanophenyl porphyrins is due to the
      negligible contribution of entropy to the relative stability of the adsorbed
      species and that the adsorption hardly changes the situation found in the gas
      phase.

PMID- 12059249
TI  - The reaction of triplet flavin with indole. A study of the cascade of reactive
      intermediates using density functional theory and time resolved infrared
      spectroscopy.
AB  - As a model for riboflavin, lumiflavin was investigated using density functional
      theory methods (B3LYP/6-31G* and B3LYP/6-31+G**) with regard to the proposed
      cascade of intermediates formed after excitation to the triplet state, followed
      by electron-transfer, proton-transfer, and radical[bond]radical coupling
      reactions. The excited triplet state of the flavin is predicted to be 42 kcal/mol
      higher in energy than the singlet ground state, and the pi radical anion lies
      45.1 kcal/mol lower in energy than the ground-state flavin and a free electron in
      the gas phase. The former value compares to a solution-phase triplet energy of
      49.8 kcal/mol of riboflavin. For the radical anion, the thermodynamically favored
      position to accept a proton on the flavin ring system is at N(5). A natural
      population analysis also provided spin density information for the radicals and
      insight into the origin of the relative stabilities of the six different
      calculated hydroflavin radicals. The resulting 5H-LF* radical can then undergo
      radical[bond]radical coupling reactions, with the most thermodynamically stable
      adduct being formed at C(4'). Vibrational spectra were also calculated for the
      transient species. Experimental time-resolved infrared spectroscopic data
      obtained using riboflavin tetraacetate are in excellent agreement with the
      calculated spectra for the triplet flavin, the radical anion, and the most stable
      hydroflavin radical.

PMID- 12059250
TI  - Determination of (1)H homonuclear scalar couplings in unlabeled carbohydrates.
AB  - The scarcity of structural information on carbohydrates results from combined
      difficulties to crystallize and the limitations in NMR analysis. Current methods
      for determining basic NMR parameters such as (1)H homonuclear scalar couplings
      are very limited, especially for large molecules such as polysaccharides,
      oligonucleotides, and the carbohydrate part of glycoproteins. In this paper, a
      NMR experiment for the determination of endocyclic (1)H homonuclear scalar
      couplings ((3)J(HH)) in unlabeled carbohydrates is presented. In addition to
      scalar couplings, cross-correlated dipole-dipole relaxation rates were measured
      for large polysaccharides. The measurement of all endocyclic homonuclear coupling
      constants within monosaccharide units is presented for lactose, a model
      disaccharide, and for a natural-abundance 2 MDa bacterial polysaccharide excreted
      by Streptococcus thermophilus Sfi39.

PMID- 12059251
TI  - Low-valent group-13 chemistry. Theoretical investigation of the structures and
      relative stabilities of donor-acceptor complexes R(3)E[bond]E'R' and their
      isomers R(2)E[bond]E'RR'.
AB  - The results of quantum chemical calculations at the gradient-corrected density
      functional theory (DFT) level with the B3LYP functional of the donor-acceptor
      complexes R(3)E[bond]E'R' and their isomers R(2)E[bond]E'RR', where E, E' =
      B[bond]Tl and R, R' = H, Cl, or CH(3), are reported. The theoretically predicted
      energy differences between the donor-acceptor form R(3)E[bond]E'R' and the
      classical isomer R(2)E[bond]E'RR' and the bond dissociation energies of the
      E[bond]E' bonds are given. The results are discussed in order to show which
      factors stabilize the isomers R(3)E[bond]E'R'. There is no simple correlation of
      the nature of the group-13 elements E, E' and the substituents R, R' with the
      stability of the complexes. The isomers R(3)E[bond]'R' come stabilized by pi
      donor groups R', while the substituents R may either be sigma- or pi-bonded
      groups. Calculations of Cl(3)B[bond]BR' [R' = Cl, cyclopentadienyl (Cp), or Cp*]
      indicate that the Cp* group has a particularly strong effect on the complex form.
      The calculations show that the experimentally known complex Cl(3)B[bond]BCp* is
      the strongest bonded donor-acceptor complex of main-group elements that has been
      synthesized until now. The theoretically predicted B[bond]B bond energy is D(o) =
      50.6 kcal/mol. However, the calculations indicate that it should also be possible
      to isolate donor-acceptor complexes R(3)E[bond]E'R' where R' is a sigma-bonded
      bulky substituent. Possible candidates that are suggested for synthetic work are
      the borane complexes (C(6)F(5))(3)B[bond]E'R' and (t)Bu(3)B[bond]E'R' (E' =
      Al[bond]Tl) and the alane complexes Cl(3)Al[bond]E'R' (E' = Ga[bond]Tl).

PMID- 12059255
TI  - Chiral lanthanide complexes: coordination chemistry and applications.

PMID- 12059256
TI  - Synthesis and structural chemistry of non-cyclopentadienyl organolanthanide
      complexes.

PMID- 12059257
TI  - Lanthanide-containing molecular and supramolecular polymetallic functional
      assemblies.

PMID- 12059258
TI  - Rare-earth transition-metal chalcogenides.

PMID- 12059259
TI  - Mono(cyclopentadienyl) complexes of the rare-earth metals.

PMID- 12059260
TI  - Being excited by lanthanide coordination complexes: aqua species, chirality,
      excited-state chemistry, and exchange dynamics.

PMID- 12059261
TI  - Inorganic lanthanide compounds with complex anions.

PMID- 12059262
TI  - Synthesis, arrangement, and reactivity of arene-lanthanide compounds.

PMID- 12059263
TI  - Chemistry of tris(pentamethylcyclopentadienyl) f-element complexes,
      (C(5)Me(5))(3)M.

PMID- 12059264
TI  - Chemistry of the lanthanides using pyrazolylborate ligands.

PMID- 12059265
TI  - Lanthanocene catalysts in selective organic synthesis.

PMID- 12059266
TI  - Lanthanide complexes in multifunctional asymmetric catalysis.

PMID- 12059267
TI  - Asymmetric catalysis and amplification with chiral lanthanide complexes.

PMID- 12059268
TI  - Rare-earth metal triflates in organic synthesis.

PMID- 12059269
TI  - Lanthanide-containing liquid crystals and surfactants.

PMID- 12059270
TI  - Plastic optical fiber lasers and amplifiers containing lanthanide complexes.

PMID- 12059272
TI  - Magnetism of lanthanides in molecular materials with transition-metal ions and
      organic radicals.

PMID- 12059271
TI  - Organo lanthanide metal complexes for electroluminescent materials.

PMID- 12059273
TI  - Lanthanide complexes in molecular recognition and chirality sensing of biological
      substrates.

PMID- 12059274
TI  - Ionic conducting lanthanide oxides.

PMID- 12059275
TI  - Periodic properties of force constants of small transition-metal and lanthanide
      clusters.

PMID- 12059276
TI  - Lanthanides in non-oxide glasses.

PMID- 12059278
TI  - Revisiting the American Nurses Association's first position on education for
      nurses.
AB  - This article presents arguments in support of the ANA's first position on
      education for nurses written in 1965 and discusses the effect of this statement
      on nursing education and practice over the past four decades. The similarity of
      the issues discussed at policy tables in 1965 and 2002 are addressed. The article
      ends with a challenge for nurses to advocate for better educated nurses with
      stakeholders, their patients and clients, in public and private sectors.

PMID- 12059279
TI  - The relevance of associate degree nursing education: past, present, future.
AB  - Associate degree nursing education remains a relevant choice for students
      entering the nursing profession. Since its introduction fifty years ago,
      associate degree nursing education has had a significant impact on the registered
      nursing population in the United States. The climate for a new type of nurse was
      created by a nursing shortage, the growth of community and junior colleges, and
      government and consumer interest. Evaluation of initial programs revealed that
      desired outcomes were met. A proliferation of associate degree nursing programs
      followed with there currently being more than 800 associate degree nursing
      programs in the nation. Controversy regarding associate degree nursing as an
      entry level for registered nurses has been evolving since its inception. Issues
      related to technical nursing versus professional nursing titles and roles, and
      differentiated roles have been divisive for the nursing profession. Current
      demographics reveal that associate degree nursing continues to make a positive
      impact on the registered nurse population, providing almost 60% of entry level
      graduates each year, and attracting a greater percentage of minority groups and
      males. Associate degree nursing representatives should be involved in defining
      the future of nursing. Societal needs for health care and individual rights for
      access to education should be considered. Collaborative efforts among the nursing
      organizations are essential to promoting recruitment and retention efforts.

PMID- 12059280
TI  - Education for professional nursing practice: looking backward into the future.
AB  - The publication of the 1965 ANA position paper calling for the baccalaureate
      degree as the minimum requirement for entry into professional nursing practice
      initiated an impassioned debate which continues to frustrate and divide nursing.
      An examination of the entry into practice debate from an educational perspective
      reveals some interesting similarities in the social and political pressures felt
      by nursing in 1965 and the challenges that exist today. In looking back at the
      course of nursing education during the past thirty-seven years, some useful
      insights emerge which can help to set direction for the future. The author argues
      that it is time to leave the old debate behind and agree on the importance of
      developing a better educated profession.

PMID- 12059281
TI  - Domestic violence, nurses, and ethics: what are the links.

PMID- 12059283
TI  - Medication administration interventions that must be performed by a registered
      nurse.

PMID- 12059284
TI  - Education for entry into nursing practice: revisited for the 21st century.
AB  - Professions progress through an expected evolutionary process. This consists of
      expanding the scientific base, creating technical workers to share in the
      essential mission of the field, standardizing and up-grading education for entry
      into practice, and moving forward with specialization. Nursing s progression has
      been spotty and incomplete, largely because of the influence of external
      communities of interest, and the fact that nurses have resisted and personalized
      decisions that are necessary for future generations. For nursing, education for
      entry into practice has been the most contentious issue in this scheme of
      professional evolution. For almost 100 years, nurses have debated "entry", but
      moved to little planned change. Rather, nursing has been swept along by a host of
      social and educational circumstances that had little to do with nursing. The
      result has been a myriad of programs with graduates used interchangeably in the
      real world. This absence of consensus within the discipline of nursing causes
      consumer confusion, seriously compromises our ability to serve the public, and is
      intimately associated with the nursing shortage of 2002. What is adequate
      educational preparation for entry into professional practice for the 21st
      Century? Agreement on this issue is an essential step towards a preferred future.
      This paper is intended to raise issues, and to stimulate discussion around these
      issues, rather than to provide answers.

PMID- 12059285
TI  - Dissipative enhancement of the response of a bistable noisy oscillator to
      external driving.
AB  - A study of the linear response susceptibility of a noisy bistable oscillator as a
      function of damping is carried out using the method of moments. It is found that
      this dependence, counterintuitively, has a nonmonotonic character and shows a
      maximum when the driving frequency is comparable to the thermal interwell hopping
      rate. The possible mechanism responsible for the occurrence of such dissipative
      sensitivity enhancement is proposed.

PMID- 12059286
TI  - Long-range magnetic interaction due to the Casimir effect.
AB  - The zero-point quantum fluctuations of the electromagnetic field in vacuum are
      known to give rise to a long-range attractive force between metal plates (Casimir
      effect). For ferromagnetic layers separated by vacuum, it is shown that the
      interplay of the Casimir effect and of the magneto-optical Kerr effect gives rise
      to a long-range magnetic interaction. The Casimir magnetic force is found to
      decay as D-1 in the limit of short distances, and as D-5 in the limit of long
      distances. Explicit expressions for realistic systems are given in the large- and
      small-distance limits. An experimental test of the Casimir magnetic interaction
      is proposed.

PMID- 12059287
TI  - Kochen-Specker theorem for finite precision spin-one measurements.
AB  - Unsharp spin-one observables arise from the fact that a residual uncertainty
      about the actual orientation of the measurement device remains. If the
      uncertainty is below a certain level, and if the distribution of measurement
      errors is covariant under rotations, a Kochen-Specker theorem for the unsharp
      spin observables follows: There are finite sets of directions such that not all
      the unsharp spin observables in these directions can consistently be assigned
      approximate truth values in a noncontextual way.

PMID- 12059288
TI  - Stability and bifurcations of the figure-8 solution of the three-body problem.
AB  - The stability properties of a recently discovered solution of the general three
      body problem with equal masses and the shape of a figure 8 are analyzed as the
      masses are varied. It is shown by numerical continuation and the evaluation of
      the characteristic multipliers that the solution is stable only in a narrow mass
      interval. Other less symmetrical and unstable solutions with equal masses in the
      same homotopy class as the figure-8 orbit have been found. The branching behavior
      is also analyzed.

PMID- 12059289
TI  - Near-horizon conformal symmetry and black hole entropy.
AB  - Near an event horizon, the action of general relativity acquires a new asymptotic
      conformal symmetry. For two-dimensional dilaton gravity, this symmetry results in
      a chiral Virasoro algebra, and Cardy's formula for the density of states
      reproduces the Bekenstein-Hawking entropy. This lends support to the notion that
      black hole entropy is controlled universally by conformal symmetry near the
      horizon.

PMID- 12059290
TI  - Estimate of the cosmological bispectrum from the MAXIMA-1 cosmic microwave
      background map.
AB  - We use the measurement of the cosmic microwave background taken during the MAXIMA
      1 flight to estimate the bispectrum of cosmological perturbations. We propose an
      estimator for the bispectrum that is appropriate in the flat sky approximation,
      apply it to the MAXIMA-1 data, and evaluate errors using bootstrap methods. We
      compare the estimated value with what would be expected if the sky signal were
      Gaussian and find that it is indeed consistent, with a chi(2) per degree of
      freedom of approximately unity. This measurement places constraints on models of
      inflation.

PMID- 12059293
TI  - Quadrupolar transitions evidenced by resonant auger spectroscopy.
AB  - From absorption spectra, the only way to bring to the fore the occurrence of
      quadrupolar transitions is to study their angular dependence. Resonant
      spectroscopies offer a new opportunity to obtain more insight into excited
      electronic states by studying lineshape and intensity of decay processes. We show
      here that resonantly excited Ti KL(2,3)L(2,3) Auger spectra of TiO2(110) carry a
      clear signature of quadrupolar transitions to localized e(g) and t(2g) d-like
      states, giving access to a direct measurement of crystal field splitting.

PMID- 12059294
TI  - O 1s --> sigma* resonance in O2: inadequacy of only two exchange-split
      components.
AB  - The O 1s-->sigma* transition below the O K-edge in O2 has been investigated by
      absorption, constant ionic state (CIS) experiments, and extensive configuration
      interaction calculations. CIS scans of the three lowest-lying final states
      reached in resonant Auger decay provide a wealth of information on energy range,
      symmetry, and spin multiplicity of the intermediate states with sigma* character.
      We conclude that the identification of only two exchange-split components is
      inadequate because a complex manifold of states with sigma* character exists with
      no unique energy difference between related states.

PMID- 12059295
TI  - Time-asymmetric fluctuations of light and the breakdown of detailed balance.
AB  - Temporal fluctuations of the light radiated by a photoemissive source are studied
      through the cross correlation of output fields. Whereas microscopic reversibility
      guarantees time-symmetric fluctuations in thermal equilibrium--where detailed
      balance holds--away from equilibrium time asymmetry is permitted. Examples of
      time asymmetry in cavity QED are reported.

PMID- 12059296
TI  - Coherent atom interactions mediated by dark-state polaritons.
AB  - We suggest a technique to induce effective, controllable interactions between
      atoms that is based on Raman scattering into an optical mode propagating with a
      slow group velocity. The resulting excitation corresponds to the creation of spin
      flipped atomic pairs in a way that is analogous to correlated photon emission in
      optical parametric amplification. The technique can be used for fast generation
      of entangled atomic ensembles, spin squeezing, and applications in quantum
      information processing.

PMID- 12059297
TI  - Resonant quenching of gas-phase Cs atoms induced by surface polaritons.
AB  - Near-field coupling between an excited atom and a surface-polariton mode can
      dramatically modify atomic branching ratios, because of surface-induced
      enhancement of a resonant decay channel. We show here that Cs(6D(3/2)) transfer
      towards Cs(7P(1/2)) (at lambda = 12.15 microm), negligible in free space, becomes
      efficient in the vicinity (< or =100 nm) of a sapphire window, due to a 12 microm
      resonance in the surface-polariton modes. The experiment relies on a selective
      reflection probing on the 7P(1/2)-10D(3/2) transition.

PMID- 12059298
TI  - Wave equation for dark coherence in three-level media.
AB  - We report the derivation of a wave equation for coherence in "dark state" two
      photon-resonance spectroscopy. One of its consequences is a dark state area
      theorem. The dark area theorem is a single ordinary differential equation which
      is globally equivalent, in a way we describe, to the full set of five coupled
      nonlinear partial differential equations that govern space-time evolution of two
      pulse coherence in a lambda medium. The predictions of the dark area theorem are
      open to test via laser spectroscopy in dilute vapors and inhomogeneously
      broadened solids.

PMID- 12059299
TI  - Nonlinear optical technique for precise retardation measurements.
AB  - We present a highly sensitive nonlinear optical technique to measure optical
      retardation. The technique is based on second-harmonic generation from thin films
      using two beams at the fundamental frequency. The sensitive polarization
      dependence of the process allows measuring optical retardation very precisely.
      The technique relies on fundamental symmetry principles and does therefore not
      require complicated experimental arrangement or data analysis. The technique was
      demonstrated by determining the retardation of a nominal half-wave plate to a
      precision and repeatability better than lambda/10(4).

PMID- 12059300
TI  - Linear superposition in nonlinear equations.
AB  - Several nonlinear systems such as the Korteweg-de Vries (KdV) and modified KdV
      equations and lambda phi(4) theory possess periodic traveling wave solutions
      involving Jacobi elliptic functions. We show that suitable linear combinations of
      these known periodic solutions yield many additional solutions with different
      periods and velocities. This linear superposition procedure works by virtue of
      some remarkable new identities involving elliptic functions.

PMID- 12059301
TI  - Measuring nonstationarity by analyzing the loss of recurrence in dynamical
      systems.
AB  - We propose a measure for nonstationarity which is based on the analysis of
      distributions of temporal distances of neighboring vectors in state space. As an
      extension of previous techniques our method does not require a partitioning of
      the time series. Moreover, the deviation of mean recurrence times from frequency
      distributions that would be expected under stationary conditions allows us to
      estimate the statistical significance of the method.

PMID- 12059292
TI  - Centrality dependence of pi(+/-), K(+/-), p, and (-)p production from sqrt[s(NN)]
      = 130 GeV Au + Au collisions at RHIC.
AB  - Identified pi(+/-), K(+/-), p, and (-)p transverse momentum spectra at
      midrapidity in sqrt[s(NN)] = 130 GeV Au+Au collisions were measured by the PHENIX
      experiment at RHIC as a function of collision centrality. Average transverse
      momenta increase with the number of participating nucleons in a similar way for
      all particle species. Within errors, all midrapidity particle yields per
      participant are found to be increasing with the number of participating nucleons.
      There is an indication that K(+/-), p, and (-)p yields per participant increase
      faster than the pi(+/-) yields. In central collisions at high transverse momenta
      (p(T) > or =2 GeV/c), (-)p and p yields are comparable to the pi(+/-) yields.

PMID- 12059302
TI  - Shape of a cracking whip.
AB  - The crack of a whip is produced by a shock wave created by the supersonic motion
      of the tip of the whip in the air. A simple dynamical model for the propagation
      and acceleration of waves in the motion of whips is presented. The respective
      contributions of tension, tapering, and boundary conditions in the acceleration
      of an initial impulse are studied theoretically and numerically.

PMID- 12059304
TI  - Asymptotic scaling laws for imploding thin fluid shells.
AB  - Scaling laws governing implosions of thin shells in converging flows are
      established by analyzing the implosion trajectories in the (A,M) parametric
      plane, where A is the in-flight aspect ratio, and M is the implosion Mach number.
      Three asymptotic branches, corresponding to three implosion phases, are
      identified for each trajectory in the limit of A,M >>1. It is shown that there
      exists a critical value gamma(cr) = 1+2/nu (nu = 1,2 for, respectively,
      cylindrical and spherical flows) of the adiabatic index gamma, which separates
      two qualitatively different patterns of the density buildup in the last phase of
      implosion. The scaling of the stagnation density rho(s) and pressure P(s) with
      the peak value M(0) of the Mach number is obtained.

PMID- 12059303
TI  - Transient vortex events in the initial value problem for turbulence.
AB  - A vorticity surge event that could be a paradigm for a wide class of bursting
      events in turbulence is studied. The coherent mechanism is characterized by
      locally transverse vortex configurations that are intrinsically helical in both
      physical and Fourier space when there is a peak of the maximum vorticity parallel
      omega parallel(infinity)(t). At no time are nonhelical, antiparallel vorticity
      elements observed. This event precedes the appearance of the traditional
      signatures of an energy cascade such as strong growth of the dissipation, spectra
      approaching -5/3, and strongly Beltramized vortex tubes. Comparing how different
      large-eddy simulations reproduce these properties demonstrates the importance of
      properly modeling nonlinear transport of both energy and helicity.

PMID- 12059305
TI  - Reentrant hexagons in non-Boussinesq Rayleigh-Benard convection: effect of
      compressibility.
AB  - We present experimental studies of a new pattern sequence observed in non
      Boussinesq convection in a compressible fluid near its gas-liquid critical point
      (CP). Besides the known hysteretic transitions among conduction state, hexagons,
      and rolls, another hysteretic transition from rolls to hexagons at higher values
      of the control parameter is found. This reentrance phenomenon is observed in a
      rather narrow range of about 60- to 100-microm cell heights and is attributed to
      large compressibility of a fluid near the CP.

PMID- 12059307
TI  - Compressible sub-Alfvenic MHD turbulence in low-beta plasmas.
AB  - We present a model for compressible sub-Alfvenic isothermal magnetohydrodynamic
      (MHD) turbulence in low- beta plasmas and numerically test it. We separate MHD
      fluctuations into three distinct families: Alfven, slow, and fast modes. We find
      that production of slow and fast modes by Alfvenic turbulence is suppressed. As a
      result, Alfven modes in compressible regime exhibit scalings and anisotropy
      similar to those in incompressible regime. Slow modes passively mimic Alfven
      modes. However, fast modes show isotropy and a scaling similar to acoustic
      turbulence.

PMID- 12059306
TI  - Measurement of x-ray pulse widths by intensity interferometry.
AB  - The pulse width of hard undulator radiation (32 ps width, energy 14 keV) was
      determined by intensity interferometry. The method, in combination with various x
      ray monochromators, enables measurements to be taken over a wide range of time
      frames, from ns to fs. The applicable target includes measurements of ultrafast x
      ray pulse widths from fourth generation synchrotron light sources.

PMID- 12059308
TI  - Criteria of phase transitions in a complex plasma.
AB  - New empirical rules for different phase transitions (including the melting of
      cubic lattices and the transitions between body-centered-cubic and face-centered
      cubic structures) are proposed. The arrangements of charged macroparticles in a
      complex "dusty" plasma are numerically investigated for the conditions of
      laboratory experiments on weakly ionized gas discharges.

PMID- 12059309
TI  - GeV electrons from ultraintense laser interaction with highly charged ions.
AB  - Ultraintense laser interactions with highly charged ions are investigated using
      three-dimensional Monte Carlo simulations. Results show that ultraenergetic GeV
      electrons may be produced for highly charged ions chosen so that their electrons
      remain bound during the rise time of the laser pulse, and so that the electrons
      are ionized when the laser is near its maximum amplitude, which satisfies the
      best injection condition for subsequent laser acceleration.

PMID- 12059310
TI  - Universal attractors of reversible aggregate-reorganization processes.
AB  - We analyze a general class of reversible aggregate-reorganization processes.
      These processes are shown to exhibit globally attracting equilibrium
      distributions, which are universal, i.e., identical for large classes of models.
      Furthermore, the analysis implies that, for studies of equilibrium properties of
      any such process, computationally expensive reorganization dynamics such as
      random walks can be replaced by more efficient yet simpler methods. As a
      particular application, our results explain the recent observation of the
      formation of similar fractal aggregates from different initial structures by
      diffusive reorganization [M. Filoche and B. Sapoval, Phys. Rev. Lett. 85, 5118
      (2000)].

PMID- 12059311
TI  - Geometrically-controlled twist transitions in nematic cells.
AB  - We study geometrically controlled twist transitions of a nematic confined between
      a sinusoidal grating and a flat substrate. In these cells, the transition to the
      twisted state is driven by surface effects. We have identified the mechanisms
      responsible for the transition analytically and used exact numerical calculations
      to study the range of surface parameters where the twist instability occurs.
      Close to these values, the cell operates under minimal external fields or
      temperature variations.

PMID- 12059312
TI  - Rotation of molecular hydrogen in Si: unambiguous identification of ortho-H(2)
      and para-D(2).
AB  - The 3618.4 and 2642.6 cm(-1) infrared absorption lines of interstitial H(2) and
      D(2) in silicon have been studied under applied uniaxial stresses. The resulting
      splittings and their small dependence on isotope establish that H(2) in Si is a
      nearly free rotor and that these lines arise from vibrational transitions between
      rovibrational states with rotational quantum number J = 1 (T(2) in T(d) symmetry)
      for ortho-H(2) and para-D(2).

PMID- 12059313
TI  - Boundary lubrication properties of materials with expansive freezing.
AB  - We have performed molecular dynamics simulations of solid-solid contacts
      lubricated by a model fluid displaying many of the properties of water,
      particularly its expansive freezing. Near the region where expansive freezing
      occurs, the lubricating film remains fluid, and the friction force decreases
      linearly as the shear velocity is reduced. No sign of stick-slip motion is
      observed, even at the lowest velocities. We give a simple interpretation of these
      results, and suggest that, in general, good boundary lubrication properties will
      be found in the family of materials with expansive freezing.

PMID- 12059314
TI  - A beaker without walls: formation of deeply supercooled binary liquid solutions
      of alcohols from nanoscale amorphous solid films.
AB  - Layered nanoscale amorphous solid films of methanol and ethanol undergo complete
      intermixing prior to the onset of measurable desorption at 120 K. This
      intermixing precedes and inhibits crystallization. Subsequent desorption of the
      film is described quantitatively by a kinetic model describing evaporation from a
      continuously mixed ideal binary liquid solution. This occurs at temperatures
      below the melting point of the binary mixture, indicating ideal behavior for the
      supercooled liquid solution. This approach provides a new method for preparing
      and examining deeply supercooled solutions.

PMID- 12059315
TI  - Nematics with quenched disorder: how long will it take to heal?
AB  - Nematics with quenched disorder have been repeatedly predicted to form glass
      phases. Here we present turbidity experiments and computer simulations aimed at
      studying glass key features such as dynamics and history dependence in randomly
      perturbed nematics. Electric field-cooling alignment has been employed to prepare
      samples in suitably oriented starting states. Remarkable remnant order and slow
      dynamics are found both by experiment and simulations, indicating that random
      disorder can, by itself, induce a nematic glass state even without perturber
      restructuring.

PMID- 12059316
TI  - Modeling elasticity in crystal growth.
AB  - A new model of crystal growth is presented that describes the phenomena on atomic
      length and diffusive time scales. The former incorporates elastic and plastic
      deformation in a natural manner, and the latter enables access to time scales
      much larger than conventional atomic methods. The model is shown to be consistent
      with the predictions of Read and Shockley for grain boundary energy, and Matthews
      and Blakeslee for misfit dislocations in epitaxial growth.

PMID- 12059317
TI  - Solvation forces in branched molecular liquids.
AB  - The solvation force of squalane confined between a silicon tip and a graphite
      surface has been measured by atomic force microscopy. This highly branched
      molecule shows oscillatory force profiles similar to those of spherical and
      linear chain molecules. Squalane molecules closest to the substrate are tightly
      bound and finer details imply that interdigitation occurs. This agrees with
      computer simulations for branched molecules but differs qualitatively from force
      balance experiments. These differences arise from the smaller confinement area
      and the different chemical nature of the surfaces.

PMID- 12059291
TI  - Search for the rare decays B-->Kl(+)l(-) and B-->K(*)l(+)l(-).
AB  - We present results from a search for the flavor-changing neutral current decays B
      ->Kl(+)l(-) and B-->K(*)l(+)l(-), where l(+)l(-) is either an e(+)e(-) or
      mu(+)mu(-) pair. The data sample comprises 22.7 x 10(6) Upsilon(4S)-->B(-)B
      decays collected with the BABAR detector at the PEP-II B Factory. We obtain the
      90% C.L. upper limits B(B-->Kl(+)l(-))<0.51 x 10(-6) and B(B-->K(*)l(+)l(-))<3.1
      x 10(-6), close to standard model predictions for these branching fractions. We
      have also obtained limits on the lepton-family-violating decays B-->Ke+/-mu(-/+)
      and B-->K(*)e(+/-)mu(-/+).

PMID- 12059318
TI  - Measurement of long-range repulsive forces between charged particles at an oil
      water interface.
AB  - Using a laser tweezers method, we have determined the long-range repulsive force
      as a function of separation between two charged, spherical polystyrene particles
      (2.7 microm diameter) present at a nonpolar oil-water interface. At large
      separations (6 to 12 microm between particle centers) the force is found to decay
      with distance to the power -4 and is insensitive to the ionic strength of the
      aqueous phase. The results are consistent with a model in which the repulsion
      arises primarily from the presence of a very small residual electric charge at
      the particle-oil interface. This charge corresponds to a fractional dissociation
      of the total ionizable (sulfate) groups present at the particle-oil surface of
      approximately 3 x 10(-4).

PMID- 12059319
TI  - Two-dimensional oxide on Pd(111).
AB  - The oxidation of Pd(111) leads to an incommensurate surface oxide, which was
      studied by the use of scanning tunneling microscopy, surface x-ray diffraction,
      high resolution core level spectroscopy, and density functional calculations. A
      combination of these methods reveals a two-dimensional structure having no
      resemblance to bulk oxides of Pd. Our study also demonstrates how the atomic
      arrangement of a nontrivial incommensurate surface can be solved by molecular
      dynamics in a case where experimental techniques alone give no solution.

PMID- 12059321
TI  - Quantum conductance in semimetallic bismuth nanocontacts.
AB  - Electronic transport properties of bismuth nanocontacts are analyzed using a low
      temperature scanning tunneling microscope. The subquantum steps observed in the
      conductance versus elongation curves give evidence of atomic rearrangements in
      the contact. The quantum nature of the conductance reveals itself through peaks
      in the conductance histograms. The shape of the curves at 77 K is described by a
      simple gliding mechanism for the contact evolution during elongation. The
      different behavior at 4 K suggests a transition from light to heavy charge
      carriers as the contact cross section is decreased.

PMID- 12059320
TI  - Coupling of the lattice and superlattice deformations and hysteresis in thermal
      expansion for the quasi-one-dimensional conductor TaS3.
AB  - An original interferometer-based setup for measurements of length of needlelike
      samples is developed, and thermal expansion of o-TaS(3) crystals is studied.
      Below the Peierls transition the temperature hysteresis of length L is observed,
      the width of the hysteresis loop deltaL/L being up to 5 x 10(-5). The behavior of
      the loop is anomalous: the length changes so that it is in front of its
      equilibrium value. The hysteresis loop couples with that of conductivity. With
      lowering the temperature down to 100 K the charge-density waves' elastic modulus
      grows achieving a value comparable with the lattice Young modulus. Our results
      could be helpful in consideration of different systems with intrinsic
      superstructures.

PMID- 12059322
TI  - Competition of static stripe and superconducting phases in
      La(1.48)Nd(0.4)Sr(0.12)CuO(4) controlled by pressure.
AB  - We have investigated the pressure effect on T(c) and the Hall coefficient in the
      static stripe-ordered phase of La(1.48)Nd(0.4)Sr(0.12)CuO(4) crystal under
      hydrostatic pressure. We found a dramatic change of the Hall coefficient and an
      abrupt increase of T(c) at low pressure of about 0.1 GPa. The results are
      indicative of a transition from one- to two-dimensional charge transport,
      associated with the suppression of low-temperature-tetragonal (LTT) phase. From
      the uniaxial pressure measurements it turns out that the observed critical change
      is induced primarily due to the in-plane compression of the CuO(2) planes which
      would make the pinning potential of the LTT lattice distortions weaker.

PMID- 12059323
TI  - Unraveling the symmetry of the hole states near the Fermi level in the MgB2
      superconductor.
AB  - We use x-ray absorption spectroscopy (XAS) and electron energy loss spectroscopy
      (EELS) to study the fine structure at the K edge of boron in MgB(2). We observe
      in XAS a peak of width 0.7 eV at the edge threshold, signaling a narrow energy
      region with empty boron p states near the Fermi level. The changes in the near
      edge structure observed in EELS with direction of the momentum transfer imply
      that these states have p(x)p(y) symmetry. Our observations are consistent with
      electronic structure calculations indicating a narrow energy window of empty
      p(x)p(y) states that falls to zero at 0.8 eV above the Fermi level. The
      disappearance of the p(x)p(y) feature in EELS at grain boundaries suggests that
      this signature may become powerful in probing superconductivity at nanoscale.

PMID- 12059324
TI  - Order and mobility of solid vortex matter in oscillatory driving currents.
AB  - We study numerically the evolution of the degree order and mobility of the vortex
      lattice under steady and oscillating applied forces. We show that the oscillatory
      motion of vortices can favor an ordered structure, even when the motion of the
      vortices is plastic when the same force is applied in a constant way. Our results
      relate the spatial order of the vortex lattice with its mobility, and they are in
      agreement with recent experiments. We predict that, in oscillating applied
      forces, the lattice orients with a principal axis perpendicular to the direction
      of motion.

PMID- 12059325
TI  - Mode locking of vortex matter driven through mesoscopic channels.
AB  - We investigated the driven dynamics of vortices confined to mesoscopic flow
      channels by means of a dc-rf interference technique. The observed mode-locking
      steps in the IV curves provide detailed information on how both the number of
      vortex rows and the lattice structure in each flow channel change with magnetic
      field. Minima in flow stress occur when an integer number of rows is moving
      coherently, while maxima appear when the incoherent motion of mixed n and n+/-1
      row configurations is predominant. Simulations show that the enhanced pinning at
      mismatch originates from quasistatic fault zones with misoriented edge
      dislocations induced by disorder in the channel edges.

PMID- 12059326
TI  - Evidence of electromagnetic absorption by collective modes in the heavy fermion
      superconductor UBe(13).
AB  - We present results of a microwave surface impedance study of the heavy fermion
      superconductor UBe(13). We clearly observe an absorption peak whose frequency and
      temperature dependence scales with the BCS gap function Delta(T). Resonant
      absorption into a collective mode, with energy approximately proportional to the
      superconducting gap, is proposed as a possible explanation. Fits to the data
      provide a simple relation between Delta(T) and the collective mode frequency.

PMID- 12059327
TI  - Coordination-number dependence of magnetic hyperfine fields at (111)Cd on Ni
      surfaces.
AB  - Ferromagnetic Ni surfaces were investigated on an atomic scale using the
      perturbed angular correlation spectroscopy probe (111)Cd. A comprehensive set of
      data for magnetic hyperfine fields (B(hf)) at various probe sites is presented. A
      field variation from -7 T in Ni bulk to the surprisingly large value of 16 T at
      the adatom position on Ni(111) is observed. A continuous nonlinear dependence is
      found, correlating the experimental B(hf) values with the number of their nearest
      Ni neighbors. The data are discussed on the basis of recent calculations on B(hf)
      values at sp-element impurities on ferromagnetic surfaces.

PMID- 12059328
TI  - Polaron percolation in diluted magnetic semiconductors.
AB  - We theoretically study the development of spontaneous magnetization in diluted
      magnetic semiconductors as arising from a percolation of bound magnetic polarons.
      Within the framework of a generalized percolation theory we derive analytic
      expressions for the Curie temperature and the magnetization in the limit of low
      carrier density, obtaining excellent quantitative agreement with Monte Carlo
      simulation results and good qualitative agreement with experimental results.

PMID- 12059329
TI  - Dynamics of a tunneling magnetic impurity: Kondo effect induced incoherence.
AB  - We study how the formation of the Kondo compensation cloud influences the
      dynamical properties of a magnetic impurity that tunnels between two positions in
      a metal. The Kondo effect dynamically generates a strong tunneling impurity
      conduction electron coupling, changes the temperature dependence of the tunneling
      rate, and may ultimately result in the destruction of the coherent motion of the
      particle at zero temperature. We find an interesting two-channel Kondo fixed
      point as well for a vanishing overlap between the electronic states that screen
      the magnetic impurity. We propose experiments where the predicted features could
      be observed.

PMID- 12059330
TI  - Spin-polarized transport across sharp antiferromagnetic boundaries.
AB  - We report spin-polarized transport experiments across antiphase domain boundaries
      which act as atomically sharp magnetic interfaces. The antiphase boundaries are
      prepared by growing Fe(3)O(4) epitaxially on MgO, the magnetic coupling over a
      large fraction of these boundaries being antiferromagnetic. Magnetoresistance
      measurements yield linear and quadratic field dependence up to the anisotropy
      field for fields applied parallel and perpendicular to the film plane,
      respectively. This behavior can be explained by a hopping model in which spin
      polarized electrons traverse an antiferromagnetic interface between two
      ferromagnetic chains.

PMID- 12059331
TI  - Angle-resolved photoemission study of the MX-chain compound [Ni(chxn)(2)Br]Br(2):
      spin-charge separation in hybridized d-p chains.
AB  - We report on the results of angle-resolved photoemission experiments on a quasi
      one-dimensional (1D) MX-chain compound [Ni(chxn)2Br]Br2, which shows a gigantic
      nonlinear optical effect. A "band" having about 500 meV energy dispersion is
      found in the first half of the Brillouin zone, but disappears at kb/pi
      approximately 1/2. These spectral features are well reproduced by the d-p chain
      model with a small charge-transfer energy Delta compared with that of 1D Cu-O
      compounds. We propose that this smaller Delta is the origin of the absence of
      clear spin-charge separation in the photoemission spectra and the strong
      nonlinear optical effect.

PMID- 12059332
TI  - Activating distillation with an infinitesimal amount of bound entanglement.
AB  - We show that bipartite quantum states of any dimension, which do not have a
      positive partial transpose (NPPT), become 1-distillable when one adds an
      infinitesimal amount of bound entanglement. To this end we investigate the
      activation properties of a new class of symmetric bound entangled states of full
      rank. It is shown that in this set there exist universal activator states capable
      of activating the distillation of any NPPT state. The result shows that even a
      small amount of bound entanglement can be useful for quantum information
      purposes.

PMID- 12059333
TI  - Bridging rate coding and temporal spike coding by effect of noise.
AB  - It is controversial whether temporal spike coding or rate coding is dominant in
      the information processing of the brain. We show by a two-layered neural network
      model with noise that, when noise is small, cortical neurons fire synchronously
      and intervals of synchronous firing robustly encode the signal information, but
      that the neurons desynchronize with moderately strong noise to encode waveforms
      of the signal more accurately. Further increase of noise just deteriorates the
      encoding. A positive role of noise in the brain is suggested in a meaning
      different from stochastic resonance, coherence resonance, and deterministic
      chaos.

PMID- 12059335
TI  - Novel colloidal crystalline states on two-dimensional periodic substrates.
AB  - We show, using numerical simulations, that a rich variety of novel colloidal
      crystalline states are realized on square and triangular two-dimensional periodic
      substrates which can be experimentally created using crossed-laser arrays. When
      there are more colloids than potential substrate minima, multiple colloids are
      trapped at each substrate minima and act as a single particle with a rotational
      degree of freedom, giving rise to a new type of orientational order. We call
      these states colloidal molecular crystals. A two-step melting can also occur in
      which individual colloidal molecules initially rotate, destroying the overall
      orientational order, followed by the onset of interwell colloidal hopping.

PMID- 12059334
TI  - Rotational drag on DNA: a single molecule experiment.
AB  - Within a single-molecule configuration, we have studied rotational drag on double
      stranded linear DNA by measuring the force during mechanical opening and closing
      of the double helix at different rates. The molecule is cranked at one end by the
      effect of unzipping and is free to rotate at the other end. In this configuration
      the rotational friction torque tau on double-stranded DNA leads to an additional
      contribution to the opening force. It is shown that the effect of rotational drag
      increases with the length of the molecule, is approximately proportional to the
      angular velocity of cranking, and we estimate that the torque tau is of the order
      of 1k(B)T for 10 000 base pairs of DNA cranked at 2000 turns per second.

PMID- 12059336
TI  - Phase behavior of colloidal molecular crystals on triangular light lattices.
AB  - We investigate the melting process of a two-dimensional charge-stabilized
      colloidal system in the presence of a triangular substrate potential. This
      potential is formed by an optical interference pattern that allows the substrate
      strength to be varied continuously. By means of an additional scanned optical
      tweezer the particle density can be adjusted to different numbers m of colloidal
      particles per substrate minima; here we concentrate on the case of trimers, i.e.,
      m = 3. Because trimers exhibit additional internal degrees of rotational freedom,
      the phase behavior of such a system is very different from homogeneous or one
      dimensional periodic substrate potentials.

PMID- 12059337
TI  - Comment on "Simple One-Dimensional Model of Heat Conduction which Obeys Fourier's
      Law".

PMID- 12059339
TI  - Complementarity for generalized observables.
AB  - We examine basic properties of complementarity by using the most general
      description of quantum observables as positive-operator measures. We show that,
      in general, two observables can be complementary or not depending on the measure
      of fluctuations adopted and that complementarity is not a symmetric relation.
      This occurs because the states that determine the measured statistics do not
      necessarily coincide with the minimum uncertainty states for the same observable.
      We also show that there are observables without a complementary observable and
      that complementarity is not preserved by the Neumark extensions.

PMID- 12059340
TI  - Quantum entropy and special relativity.
AB  - We consider a single free spin- 1 / 2 particle. The reduced density matrix for
      its spin is not covariant under Lorentz transformations. The spin entropy is not
      a relativistic scalar and has no invariant meaning.

PMID- 12059341
TI  - Internal waves and synchronized precession in a cold vapor.
AB  - Exchange in a Boltzmann gas of bosons with several internal states leads to
      collective transport of internal polarization. The internal dynamics can be
      understood as Larmor precession in the presence of a torque induced by atoms on
      each other via exchange coupling. A generalized Bloch equation that includes
      interatomic exchange effects as well as orbital motion in the gas is derived and
      used to interpret a recent experiment by Lewandowski et al. as an excitation of a
      collective wave of internal state polarization. It is shown that exchange leads
      to formation of domains in which precession frequencies are synchronized.

PMID- 12059342
TI  - Internal state conversion in ultracold gases.
AB  - We consider an ultracold gas of (noncondensed) bosons or fermions with two
      internal states, and we study the effect of a gradient of the transition
      frequency between these states. When a pi/2 rf pulse is applied to the sample,
      exchange effects during collisions transfer the atoms into internal states which
      depend on the direction of their velocity. This results, after a short time, in a
      spatial separation between the two states. A kinetic equation is solved
      analytically and numerically; the results agree well with the recent observations
      of Lewandowski et al.

PMID- 12059343
TI  - Longitudinal spin waves in a dilute bose gas.
AB  - We present a kinetic theory for a dilute noncondensed Bose gas of two-level atoms
      that predicts the transient spin segregation observed in a recent experiment. The
      underlying mechanism driving spin currents in the gas is due to a mean-field
      effect arising from the quantum interference between the direct and exchange
      scattering of atoms in different spin states. We numerically solve the spin
      Boltzmann equation, using a one-dimensional model, and find excellent agreement
      with experimental data.

PMID- 12059344
TI  - Quadratic bell inequalities as tests for multipartite entanglement.
AB  - This Letter presents quantum mechanical inequalities which distinguish, for
      systems of n spin- 1 / 2 particles ( n>2), between fully entangled states and
      states in which at most n-1 particles are entangled. These inequalities are
      stronger than those obtained by Gisin and Bechmann-Pasquinucci [Phys. Lett. A
      246, 1 (1998)] and by Seevinck and Svetlichny [quant-ph/0201046].

PMID- 12059345
TI  - Noise activated nonlinear dynamic sensors.
AB  - We introduce a novel dynamical description for a wide class of nonlinear physical
      sensors operating in a noisy environment. The presence of unknown physical
      signals is assessed via the monitoring of the residence times in the metastable
      attractors of the system. We show that the presence of ambient noise, far from
      degrading the sensor operation, can actually improve its sensitivity and provide
      a greatly simplified readout scheme, as well as significantly reduce processing
      procedures for this new class of devices that we propose to call noise activated
      nonlinear dynamic sensors. Such devices can also show interesting dynamical
      features such as the resonant trapping effect.

PMID- 12059346
TI  - Noise-induced phase synchronization and synchronization transitions in chaotic
      oscillators.
AB  - Whether common noise can induce complete synchronization in chaotic systems has
      been a topic of great relevance and long-standing controversy. We first clarify
      the mechanism of this phenomenon and show that the existence of a significant
      contraction region, where nearby trajectories converge, plays a decisive role.
      Second, we demonstrate that, more generally, common noise can induce phase
      synchronization in nonidentical chaotic systems. Such a noise-induced
      synchronization and synchronization transitions are of special significance for
      understanding neuron encoding in neurobiology.

PMID- 12059347
TI  - String inspired brane world cosmology.
AB  - We consider brane world scenarios including the leading correction to the
      Einstein-Hilbert action suggested by superstring theory, the Gauss-Bonnet term.
      We obtain and study the complete set of equations governing the cosmological
      dynamics. We find they have the same form as those in Randall-Sundrum scenarios
      but with time-varying four-dimensional gravitational and cosmological constants.
      By studying the bulk geometry we show that this variation is produced by bulk
      curvature terms parametrized by the mass of a black hole. Finally, we show there
      is a coupling between these curvature terms and matter that can be relevant for
      early universe cosmology.

PMID- 12059348
TI  - Experimental demonstration of a squeezing-enhanced power-recycled michelson
      interferometer for gravitational wave detection.
AB  - Interferometric gravitational wave detectors are expected to be limited by shot
      noise at some frequencies. We experimentally demonstrate that a power recycled
      Michelson with squeezed light injected into the dark port can overcome this
      limit. An improvement in the signal-to-noise ratio of 2.3 dB is measured and
      locked stably for long periods of time. The configuration, control, and signal
      readout of our experiment are compatible with current gravitational wave detector
      designs. We consider the application of our system to long baseline
      interferometer designs such as LIGO.

PMID- 12059349
TI  - Constraining dark energy with Sunyaev-Zel'dovich cluster surveys.
AB  - We discuss the prospects of constraining the properties of a dark energy
      component, with particular reference to a time varying equation of state, using
      future cluster surveys selected by their Sunyaev-Zel'dovich effect. We compute
      the number of clusters expected for a given set of cosmological parameters and
      propogate the errors expected from a variety of surveys. In the short term they
      will constrain dark energy in conjunction with future observations of type Ia
      supernovae, but may in time do so in their own right.

PMID- 12059350
TI  - Photon propagator, monopoles, and the thermal phase transition in three
      dimensional compact QED.
AB  - We investigate the gauge boson propagator in the three dimensional compact
      Abelian gauge model in the Landau gauge at finite temperature. The presence of
      the monopole plasma in the confinement phase leads to the appearance of an
      anomalous dimension in the momentum dependence of the propagator. The anomalous
      dimension as well as an appropriate ratio of photon wave function renormalization
      constants with and without monopoles is observed to be an order parameter for the
      deconfinement phase transition. We discuss the relation between our results and
      the confining properties of the gluon propagator in non-Abelian gauge theories.

PMID- 12059352
TI  - Anomaly, gauge and gaugino mediation in brane worlds with messenger matter.
AB  - Theories in which supersymmetry is broken on another brane, which is separated
      from the minimal supersymmetry standard model (MSSM) matter fields in an extra
      dimension, are attractive because they may solve the supersymmetric flavor
      problem. We consider the effects in such theories of new messenger fields with
      standard model gauge charges and with direct couplings to the supersymmetry
      breaking sector. The effect on the masses of the MSSM superpartners can be
      dramatic. In particular, the tachyonic slepton problem of anomaly mediation and
      the stable slepton problem of gaugino mediation can be cured.

PMID- 12059354
TI  - Deconfinement transition in three-dimensional compact U(1) gauge theories coupled
      to matter fields.
AB  - It is shown that permanent confinement in three-dimensional compact U(1) gauge
      theory can be destroyed by matter fields in a deconfinement transition. This
      follows from a nontrivial infrared fixed point caused by matter, and an anomalous
      scaling dimension of the gauge field. This leads to a logarithmic interaction
      between the defects of the gauge fields, which form a gas of magnetic monopoles.
      For logarithmic interactions, the original electric charges are unconfined. The
      confined phase, which is permanent in the absence of matter fields, is reached at
      a critical electric charge, where the interaction between magnetic charges is
      screened by a pair-unbinding in a Kosterlitz-Thouless-like phase transition.

PMID- 12059356
TI  - J/psi suppression in nucleus-nucleus collisions.
AB  - We propose a model for calculating J/psi suppression in high-energy hadron
      nucleus and nucleus-nucleus collisions. We factorized the process into a
      production of the cc- pairs convoluted with a transition probability into the
      observed J/psi mesons. As the produced cc- pairs exit the nuclear matter,
      multiple scattering increases the square of the relative momentum between the c
      and c- such that some pairs are transmuted into open charm states. With only one
      parameter, the energy gained by the produced cc- pair per unit length in the
      nuclear medium, our model can fit all observed J/psi suppression data in hadron
      nucleus and nucleus-nucleus collisions.

PMID- 12059357
TI  - J/psi suppression in Pb + Pb collisions: a conventional description.
AB  - We have analyzed the latest NA50 data on J/psi suppression in Pb + Pb collisions.
      J/psi production is assumed to be a two-step process: (i) formation of a cc-
      pair, which is accurately calculable in QCD, and (ii) formation of a J/psi meson
      from the cc- pair, which can be conveniently parametrized. The parameters of the
      model were fixed from experimental data on the total J/psi cross section as a
      function of effective nuclear length. The model gives an excellent description of
      NA50 data on the ET dependence of the J/psi-to-Drell-Yan ratio. It was applied to
      the ET dependence of J/psi at RHIC energies, and predicts a much larger
      suppression of J/psi, in agreement with other model calculations.

PMID- 12059353
TI  - Improved measurement of Vub with inclusive semileptonic B decays.
AB  - We report a new measurement of the Cabibbo-Kobayashi-Maskawa parameter Vub made
      with a sample of 9.7 x 10(6) BB- events collected with the CLEO II detector.
      Using heavy quark theory, we combine the observed yield of leptons from
      semileptonic B decay in the end-point momentum interval 2.2-2.6 GeV/c with recent
      CLEO II data on B-->X(s)gamma to find Vub = (4.08+/-0.34+/-0.44+/-0.16+/
      0.24)x10(-3), where the first two uncertainties are experimental and the last two
      are from theory.

PMID- 12059358
TI  - Cronin effect in hadron production off nuclei.
AB  - Recent data from RHIC for high- pT hadrons raised again the long-standing problem
      of quantitatively understanding the Cronin effect, i.e., nuclear enhancement of
      high- pT hadrons. All existing models for the Cronin effect rely on a fit to the
      data to be explained. We develop a phenomenological description based on the
      light-cone QCD-dipole approach which allows one to explain data without fitting
      to them and to provide predictions for pA collisions at RHIC and LHC. We point
      out that the underlying mechanism drastically changes with energy, from
      incoherent production of high- pT hadrons on different nucleons at low energies,
      to an entirely coherent process at very high energies.

PMID- 12059359
TI  - B(E2) values in 150Nd and the critical point symmetry X(5).
AB  - Lifetimes of states in 150Nd were measured using the recoil distance method
      following Coulomb excitation of 150Nd by a 132 MeV 32S beam. The experiment was
      performed at the Yale Tandem accelerator, employing the SPEEDY gamma-ray detector
      array and the New Yale Plunger Device. Reduced transition probabilities in 150Nd
      are compared to the predictions of the critical point symmetry X(5) of the
      phase/shape transition that occurs for the N = 90 rare earth isotones. Very good
      agreement was observed between the parameter-free (apart from scale) X(5)
      predictions and the low-spin level scheme of 150Nd, revealing this as the best
      case thus far for the realization of the X(5) symmetry.

PMID- 12059355
TI  - Helicity amplitudes A1/2 and A3/2 for the D13(1520) resonance obtained from the
      gamma-->p-->-->ppi(0) Reaction.
AB  - The helicity dependence of the gamma-->p-->-->ppi(0) reaction has been measured
      for the first time in the photon-energy range from 550 to 790 MeV. The
      experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a
      circularly polarized, tagged photon beam, and a longitudinally polarized frozen
      spin target. These data are predominantly sensitive to the D13(1520) resonance
      and are used to determine its helicity amplitudes.

PMID- 12059360
TI  - Suppression of multiple ionization of atomic ions in intense ultrafast laser
      pulses.
AB  - The interaction of an intense laser field with a beam of atomic ions has been
      investigated experimentally for the first time. The ionization dynamics of Ar+
      ions and Ar neutrals in a 60 fs, 790 nm laser pulse have been compared and
      contrasted at intensities up to 10(16) W cm-2. Our results show that
      nonsequential ionization from an Ar+ target is strongly suppressed compared with
      that from the corresponding neutral target. We have also observed for the first
      time the strong field ionization of high lying target metastable levels in the
      Ar+ beam.

PMID- 12059361
TI  - Bubble formation and decay in 3He and 4He clusters.
AB  - The energy transfer in 3He and 4He clusters electronically excited by
      monochromatic synchrotron radiation is investigated by luminescence spectroscopy.
      Depending on the cluster size and the isotopic constitution, either sharp,
      broadened, or shifted emission bands of single He molecules are observed. The
      spectral features show that He molecules emit light either within a bubble inside
      the cluster or in the vacuum after desorption from the cluster. From the
      luminescence intensity, the cluster diameter, and the radiative lifetime, an
      average velocity of approximately 7 m/s of bubbles in 4He clusters could be
      deduced. In the nonsuperfluid 3He clusters this velocity was observed to be
      significantly lower.

PMID- 12059362
TI  - Orientation of polar molecules by laser induced adiabatic passage.
AB  - We show that two overlapping linearly polarized laser pulses of frequencies omega
      and its second harmonic 2omega can strongly orient linear polar molecules, by
      adiabatic passage along dressed states. The resulting robust orientation can be
      interpreted as a laser-induced localization in the effective double well
      potential created by the fields, which induces a preliminary molecular alignment.
      The direction of the orientation can be selected by the relative phase of the
      fields.

PMID- 12059363
TI  - Sum-frequency generation in dissipative systems: experimental evidence for
      optical wave patterns.
AB  - We report a new mechanism for the secondary instabilities of traveling wave
      patterns in dissipative systems. In close analogy to nonlinear optics and plasma
      physics, it is a process of three-wave interaction that leads to sum-frequency
      generation. The primary traveling wave gives rise to two additional wave
      components, an upper and a lower frequency. We outline the mechanism and we show
      that this process does occur for wave patterns obtained in an optical experiment.

PMID- 12059364
TI  - Phase-space transport of stochastic chaos in population dynamics of virus spread.
AB  - A general way to classify stochastic chaos is presented and applied to population
      dynamics models. A stochastic dynamical theory is used to develop an algorithmic
      tool to measure the transport across basin boundaries and predict the most
      probable regions of transport created by noise. The results of this tool are
      illustrated on a model of virus spread in a large population, where transport
      regions reveal how noise completes the necessary manifold intersections for the
      creation of emerging stochastic chaos.

PMID- 12059365
TI  - Ordered clusters and dynamical states of particles in a vibrated fluid.
AB  - Fluid-mediated interactions between particles in a vibrating fluid lead to both
      long range attraction and short range repulsion. The resulting patterns include
      hexagonally ordered microcrystallites, time-periodic structures, and chaotic
      fluctuating patterns with complex dynamics. A model based on streaming flow gives
      a good quantitative account of the attractive part of the interaction.

PMID- 12059366
TI  - Pattern dynamics of vortex ripples in sand: nonlinear modeling and experimental
      validation.
AB  - Vortex ripples in sand are studied experimentally in a one-dimensional setup with
      periodic boundary conditions. The nonlinear evolution, far from the onset of
      instability, is analyzed in the framework of a simple model developed for
      homogeneous patterns. The interaction function describing the mass transport
      between neighboring ripples is extracted from experimental runs using a recently
      proposed method for data analysis, and the predictions of the model are compared
      to the experiment. An analytic explanation of the wavelength selection mechanism
      in the model is provided, and the width of the stable band of ripples is
      measured.

PMID- 12059367
TI  - Influence of stagnant zones on transient and asymptotic dispersion in
      macroscopically homogeneous porous media.
AB  - The role of stagnant zones in hydrodynamic dispersion is studied for creeping
      flow through a fixed bed of spherical permeable particles, covering several
      orders of characteristic time and length scales associated with fluid transport.
      Numerical simulations employ a hierarchical model to cope with the different
      temporal and spatial scales, showing good agreement with our experimental results
      on diffusion-limited mass transfer, transient, and asymptotic longitudinal
      dispersion. These data demonstrate that intraparticle liquid holdup in
      macroscopically homogeneous porous media clearly dominates over contributions
      caused by the intrinsic flow field heterogeneity and boundary-layer mass
      transfer.

PMID- 12059368
TI  - Evidence for microbunching "sidebands" in a saturated free-electron laser using
      coherent optical transition radiation.
AB  - We report the first measurements of z-dependent coherent optical transition
      radiation (COTR) due to electron-beam microbunching at high gains ( >10(4))
      including saturation of a self-amplified spontaneous emission free-electron laser
      (FEL). In these experiments the fundamental wavelength was near 530 nm, and the
      COTR spectra exhibit the transition from simple spectra to complex spectra ( 5%
      spectral width) after saturation. The COTR intensity growth and angular
      distribution data are reported as well as the evidence for transverse spectral
      dependencies and an "effective" core of the beam being involved in microbunching.

PMID- 12059369
TI  - Indirect-drive inertial confinement fusion using highly supersonic, radiatively
      cooled, plasma slugs.
AB  - We present a new approach to indirect-drive inertial confinement fusion which
      makes use of highly supersonic, radiatively cooled, slugs of plasma to energize a
      hohlraum. 2D resistive magnetohydrodynamic simulations of slug formation in
      shaped liner Z-pinch implosions are presented along with 2D-radiation
      hydrodynamic simulations of the slug impacting a converter foil and 3D-view
      factor simulations of a double-ended hohlraum. Results for the Z facility at
      Sandia National Laboratory indicate that two synchronous slugs of 250 kJ kinetic
      energy could be produced, resulting in a capsule surface temperature of
      approximately 225 eV.

PMID- 12059370
TI  - Anomalous absorption of high-energy green laser light in high- z plasmas.
AB  - We observe strong anomalous absorption of green laser light in mm-scale high
      temperature gold plasmas. Both the laser light absorption and the resulting
      increase of the electron temperature, which was measured independently with
      Thomson scattering, have been successfully modeled by including enhanced
      collisions due to heat-flux driven ion acoustic fluctuations. Calculations that
      include only inverse bremsstrahlung significantly underestimate the experimental
      laser absorption and the electron temperature.

PMID- 12059371
TI  - Mode locking in reversed-field pinch experiments.
AB  - The MHD mode trajectory in the Madison Symmetric Torus reversed-field pinch has
      been found to obey the sine-Gordon equation. Corresponding to experiment, a
      perturbation analysis predicts the locations of mode locking to be at the vacuum
      chamber poloidal and/or toroidal gaps. The mode's energy dissipates when it
      locks, as shown by a decaying spiral phase-plane trajectory. Unlocked modes
      travel around the torus without an abrupt energy loss. By varying key machine
      parameters obtained by statistical analysis, the probability of locking in
      accordance with the experimental results can be predicted.

PMID- 12059372
TI  - Suppression of superluminous precursors in high-power backward Raman amplifiers.
AB  - The very promising scheme for producing ultrapowerful laser pulses through Raman
      backscattering of pump lasers in plasmas can be jeopardized by superluminous
      precursors. Growing from the leading part of the Raman pumped seed pulse, these
      precursors can disturb the plasma and the pump ahead of the pumped pulse. These
      ruinous effects, however, might be averted by a detuning, large enough to
      suppress the precursors, yet small enough to allow the desired backscatter
      effect.

PMID- 12059373
TI  - A fourfold coordinated point defect in silicon.
AB  - Vacancies, interstitials, and Frenkel pairs are considered to be the basic point
      defects in silicon. We challenge this point of view by presenting density
      functional calculations that show that there is a stable point defect in silicon
      that has fourfold coordination and is lower in energy than the traditional
      defects.

PMID- 12059374
TI  - Equation of state data for iron at pressures beyond 10 Mbar.
AB  - We present equation of state points for iron, in the pressure range 10-45 Mbar,
      the first obtained with laser-driven shock waves. The experiment has been
      performed with the high energy laser Phebus, optically smoothed with Kinoform
      phase plates. Our results double the set of existing experimental data at very
      high pressures showing good agreement with the predictions of the quotidian
      equation of state model and with previous results.

PMID- 12059351
TI  - Search for T and CP violation in B0-B-0 mixing with inclusive dilepton events.
AB  - We report the results of a search for T and CP violation in B0-B-0 mixing using
      an inclusive dilepton sample collected by the BABAR experiment at the PEP-II B
      Factory. The asymmetry between l+l+ and l-l- events allows us to compare the
      probabilities for B-0-->B0 and B0-->B-0 oscillations and thus probe T and CP
      invariance. Using a sample of 23 x 10(6) BB- pairs, we measure a same-sign
      dilepton asymmetry of A(T/CP) = [0.5+/-1.2(stat)+/-1.4(syst)]%. For the modulus
      of the ratio of complex mixing parameters p and q, we obtain q/p = 0.998+/
      0.006(stat)+/-0.007(syst).

PMID- 12059375
TI  - Thermodynamics of the superfluid dilute bose gas with disorder.
AB  - We generalize the Beliaev-Popov diagrammatic technique for the problem of
      interacting dilute Bose gas with weak disorder. Averaging over disorder is
      implemented by the replica method. The low-energy asymptotic form of the Green
      function confirms that the low-energy excitations of the superfluid dirty-boson
      system are sound waves with velocity renormalized by the disorder and additional
      dissipation due to the impurity scattering. We find the thermodynamic potential
      and the superfluid density at any temperature below the superfluid transition
      temperature (but outside the Ginzburg region) and derive the phase diagram in
      temperature vs disorder plane.

PMID- 12059377
TI  - Tip splittings and phase transitions in the dielectric breakdown model: mapping
      to the diffusion-limited aggregation model.
AB  - We show that the fractal growth described by the dielectric breakdown model
      exhibits a phase transition in the multifractal spectrum of the growth measure.
      The transition takes place because the tip splitting of branches forms a fixed
      angle. This angle is eta dependent but it can be rescaled onto an "effectively"
      universal angle of the diffusion-limited aggregation branching process. We derive
      an analytic rescaling relation which is in agreement with numerical simulations.
      The dimension of the clusters decreases linearly with the angle and the growth
      becomes non-ractal at an angle close to 74 degrees (which corresponds to eta =
      4.0+/-0.3).

PMID- 12059376
TI  - Metal-encapsulated caged clusters of germanium with large gaps and different
      growth behavior than silicon.
AB  - Metal ( M)-encapsulated caged clusters of Ge are studied using the ab initio
      pseudopotential plane-wave method and the generalized gradient approximation for
      the exchange-correlation energy. Depending upon the size of the M atom, we find
      Frank-Kasper polyhedral M@Ge(16) for M= Ti, Zr, Hf, and capped decahedral or
      cubic M@Ge(14) and M@Ge(15) clusters for several M atoms. The growth behavior
      differs from the one found in M@Si(n) clusters. The highest-occupied-lowest
      unoccupied molecular orbital gaps are, however, similarly large or even higher in
      some cases. Cr@Ge(16) and Fe@Ge(15) are magnetic. The weak interaction between
      the clusters makes such species attractive for cluster assembled materials.

PMID- 12059378
TI  - Phonon softening in metallic nanotubes by a Peierls-like mechanism.
AB  - The radial dependency of the vibrational frequencies of single-wall carbon
      nanotubes in the G band (1500-1600 cm(-1)) is studied by density functional
      theory. In metallic nanotubes, a mode with A1 symmetry is found to be
      significantly softer than the corresponding mode in insulating tubes or graphite.
      The mechanism that leads to the mode softening is explored. It is reminiscent of
      the driving force inducing Peierls distortions. At ambient temperature, the
      energy gained by opening the gap is, however, not sufficient for a static lattice
      distortion. Instead the corresponding vibrational frequency is lowered.

PMID- 12059379
TI  - Novel pattern forming process due to the coupling of convection and phase change.
AB  - We present a novel mechanism of pattern formation behind a flat interface during
      directional solidification of peritectic alloys. It is shown through
      computational modeling that irregular oscillatory thermosolutal convection can
      develop in the vertical Bridgman system, even with bottom seeding and bottom
      cooling. The coupling of the flow oscillation near the interface with
      solidification leads to ordered layered structures in the solidified crystal,
      which agree closely with earlier experimental results.

PMID- 12059380
TI  - Dewetting of glassy polymer films.
AB  - Dynamics and morphology of hole growth in a film of power hardening viscoplastic
      solid [ yield stress approximately (strain-rate)(n)] is investigated. At short
      times the growth is exponential and depends on the initial hole size. At long
      times, for n>1 / 3, the growth is again exponential but with a different
      exponent. However, for n<1 / 3 the hole growth slows and the hole radius
      approaches an asymptotic value at long times. The rim shape is highly asymmetric,
      the height of which has a power law dependence on the hole radius (exponent close
      to unity for 0.25<n<0.4). The above results explain recent intriguing experiments
      of Reiter [Phys. Rev. Lett., 87, 186 101 (2001)] on dewetting.

PMID- 12059381
TI  - Non-nearest-neighbor jumps in 2D diffusion: Pd on W(110).
AB  - A variety of jumps has in the past been identified in diffusion of atoms on 1D
      channeled surfaces. To establish the jump processes important in diffusion on a
      2D surface, the movement of individual Pd atoms has been examined on W(110). From
      the distribution of displacements of Pd at high temperatures, double jumps are
      found along the close-packed <111>. For the first time, sizable differences are
      also observed between the mean-square displacements along x and y, which
      demonstrate unexpected contributions from jumps along <110>, but not along <001>.
      These jumps proceed over activation barriers higher than for single jumps, under
      conditions predicted from previous work with Pd on the channeled W(211).

PMID- 12059382
TI  - Onset of glassy dynamics in a two-dimensional electron system in silicon.
AB  - The fluctuations of conductivity sigma with time have been studied in a two
      dimensional electron system in low-mobility Si inversion layers. The noise power
      spectrum is approximately 1/f(alpha) with alpha exhibiting a sharp jump at an
      electron density n(s) = n(g). A huge increase in the relative variance of sigma
      is observed as n(s) is reduced below n(g), reflecting a dramatic slowing down of
      the electron dynamics. This is attributed to the freezing of the electron glass.
      The data strongly suggest that glassy dynamics persists in the metallic phase.

PMID- 12059383
TI  - Quenching of majority-channel quasiparticle excitations in cobalt.
AB  - The low-energy electronic excitations in cobalt are studied by a theoretical
      method that includes many-body effects and a realistic description of the band
      structure. Angle-resolved photoemission spectra measured on a thick film of
      hexagonal close-packed Co on Cu(111) agree well with calculated spectral
      functions. Because of many-body effects no sharp quasiparticle peaks exist for
      binding energies larger than 2 eV and in this energy region the spectrum is
      essentially incoherent. The many-body corrections are much stronger in the
      majority-spin channel and drastically affect the spin polarization of the
      spectra.

PMID- 12059384
TI  - Fermi surface of 3d1 perovskite CaVO3 near the Mott transition.
AB  - We present a detailed de Haas-van Alphen effect study of the perovskite CaVO3,
      offering an unprecedented test of electronic structure calculations in a 3d
      transition metal oxide. Our experimental and calculated Fermi surfaces are in
      good agreement, but only if we ignore large orthorhombic distortions of the cubic
      perovskite structure. Subtle discrepancies may shed light on an apparent conflict
      between the low energy properties of CaVO3, which are those of a simple metal,
      and high energy probes which reveal strong correlations that place CaVO3 on the
      verge of a metal-insulator transition.

PMID- 12059385
TI  - Mechanisms of spin-polarized current-driven magnetization switching.
AB  - The mechanisms of the magnetization switching of magnetic multilayers driven by a
      current are studied by including exchange interaction between local moments and
      spin accumulation of conduction electrons. It is found that this exchange
      interaction leads to two additional terms in the Landau-Lifshitz-Gilbert
      equation: an effective field and a spin torque. Both terms are proportional to
      the transverse spin accumulation and have comparable magnitudes.

PMID- 12059386
TI  - Viscous fingering and the shape of an electronic droplet in the quantum Hall
      regime.
AB  - We show that the semiclassical dynamics of an electronic droplet, confined in a
      plane in a quantizing inhomogeneous magnetic field in the regime where the
      electrostatic interaction is negligible, is similar to viscous (Saffman-Taylor)
      fingering on the interface between two fluids with different viscosities confined
      in a Hele-Shaw cell. Both phenomena are described by the same equations with
      scales differing by a factor of up to 10(-9). We also report the quasiclassical
      wave function of the droplet in an inhomogeneous magnetic field.

PMID- 12059387
TI  - Nonequilibrium transport through a vertical quantum dot in the absence of spin
      flip energy relaxation.
AB  - We investigate nonequilibrium transport in the absence of spin-flip energy
      relaxation in a few-electron quantum dot artificial atom. Novel nonequilibrium
      tunneling processes involving high-spin states, which cannot be excited from the
      ground state because of spin blockade, and other processes involving more than
      two charge states are observed. These processes cannot be explained by orthodox
      Coulomb blockade theory. The absence of effective spin relaxation induces
      considerable fluctuation of the spin, charge, and total energy of the quantum
      dot. Although these features are revealed clearly by pulse excitation
      measurements, they are also observed in conventional dc current characteristics
      of quantum dots.

PMID- 12059388
TI  - Effects of crystal shape on the energy levels of zero-dimensional PbS quantum
      dots.
AB  - Nanometer-size PbS quantum dots have been made by electrodeposition on a Au(111)
      substrate. The deposited nanocrystals have a flattened cubic shape. We probed the
      single-electron energy-level spectrum of individual quantum dots by scanning
      tunneling spectroscopy and found that it deviates strongly from that of spherical
      PbS quantum dots. The measured energy-level spectrum is successfully explained by
      considering strong confinement in a flattened cubic box.

PMID- 12059389
TI  - Tunneling and nonhyperbolicity in quantum dots.
AB  - We argue that many major features in electronic transport in realistic quantum
      dots are not explainable by the usual semiclassical approach, due to the
      contributions of the quantum-mechanical tunneling of the electrons through the
      Kolmogorov-Arnol'd-Moser islands. We show that dynamical tunneling gives rise to
      a set of resonances characterized by two quantum numbers, which leads to
      conductance oscillations and concentration of wave functions near stable and
      unstable periodic orbits. Experimental results agree very well with our
      theoretical predictions, indicating that tunneling has to be taken into account
      to understand the physics of transport in generic nanostructures.

PMID- 12059390
TI  - Observation of structures of chain vortices inside anisotropic high- Tc
      superconductors.
AB  - In order to elucidate the formation mechanism of unconventional arrangements of
      vortices in high- Tc superconducting thin films at an inclined magnetic field to
      the layer plane, we investigated the structures of vortex lines inside the films
      by Lorentz microscopy using our 1-MV field-emission electron microscope. Our
      observation results concluded that vortex lines are tilted to form linear chains
      in YBaCu3O(7,8). Vortex lines in the chain-lattice state in
      Bi2Sr2CaCu2O(8+delta), on the other hand, are all perpendicular to the layer
      plane, and therefore only vortices lined up along Josephson vortices form chains.

PMID- 12059391
TI  - Heterogeneous aging in spin glasses.
AB  - We introduce a set of theoretical ideas that form the basis for an analytical
      framework capable of describing nonequilibrium dynamics in glassy systems. We
      test the resulting scenario by comparing its predictions with numerical
      simulations of short-range spin glasses. Local fluctuations and responses are
      shown to be connected by a generalized local out-of-equilibrium fluctuation
      dissipation relation. Scaling relationships are uncovered for the slow evolution
      of heterogeneities at all time scales.

PMID- 12059392
TI  - Scaling approach to the magnetic phase diagram of nanosized systems.
AB  - Based on the discovery of a simple scaling relation, a new technique for the
      investigation of the phase diagram of nanosized magnetic systems is proposed. By
      scaling the exchange interaction between magnetic moments, the magnetic phase
      diagram of currently lithographically produced particles can be obtained from
      those corresponding to much smaller systems. Such a technique reduces the
      computation time by several orders of magnitude, and provides a new approach to
      the investigation of the relative stability of distinct internal magnetic
      configurations of nanosized systems. The technique is illustrated by the
      determination of the phase diagram of cylindrically shaped Co particles.

PMID- 12059393
TI  - Unusual nature of ferromagnetism coexisting with superconductivity in UGe2.
AB  - We report the discovery of a jump in the magnetization of a macroscopic single
      crystalline sample of UGe2 that shows coexistence of ferromagnetism and
      superconductivity. In particular, we observe that the jump occurs at regular
      intervals of field and only at very low temperatures. This novel feature implies
      that the magnetic field induces a sudden change of the direction of the
      magnetization between two equivalent easy axes of magnetization even in a
      macroscopic sample. We ascribe it to a field-tuned resonant tunneling between
      quantum spin states, and we propose that the size of a magnetic domain is smaller
      than a superconducting coherence length.

PMID- 12059394
TI  - Chiral fluctuations in MnSi above the Curie temperature.
AB  - Polarized neutrons are used to determine the antisymmetric part of the magnetic
      susceptibility in noncentrosymmetric MnSi. The paramagnetic fluctuations are
      found to be incommensurate with the chemical lattice and to have a chiral
      character. We argue that antisymmetric interactions must be taken into account to
      properly describe the critical dynamics in MnSi above T(C). The possibility of
      directly measuring the polarization dependent part of the dynamical
      susceptibility in a large class of compounds by polarized inelastic neutron
      scattering is outlined as it can yield evidence for antisymmetric interactions
      such as spin-orbit coupling in metals as well as in insulators.

PMID- 12059395
TI  - SU(2) instantons with boundary jumps and spin tunneling in magnetic molecules.
AB  - Coherent state path integrals are shown in general to contain instantons with
      jumps at the boundaries, i.e., boundary points lying outside classical phase
      space. Inclusion of these instantons is shown to resolve the "missing quench
      paradox" in the magnetic molecule Fe8, i.e., the fact that the tunneling between
      the ground Zeeman states of this molecule is quenched at only four magnetic field
      values, instead of the ten that would be expected from the topological Berry
      phase between interfering instantons. An approximate formula is found for the
      location of the four remaining quenches.

PMID- 12059396
TI  - Solution of the two-channel Anderson impurity model: implications for the heavy
      fermion UBe13.
AB  - We solve the two-channel Anderson impurity model using the Bethe-ansatz. We
      determine the ground state and derive the thermodynamics, obtaining the impurity
      entropy and specific heat over the full range of temperature. We show that the
      low-temperature physics is given by a line of fixed points describing a two
      channel non-Fermi-liquid behavior in the integral valence regime associated with
      moment formation as well as in the mixed valence regime where no moment forms. We
      discuss the relevance for the theory of UBe13.

PMID- 12059398
TI  - Tailoring confining barriers for surface states by step decoration: CO /vicinal
      Cu(111).
AB  - The influence of CO adsorption on the Shockley type surface state on vicinal
      Cu(111) surfaces is investigated using angle resolved photoemission. As the steps
      are decorated with CO the surface state shifts to higher binding energies, which
      is opposite to the known behavior on flat Cu(111). This is described within a one
      dimensional potential model in which clean steps represent repulsive barriers and
      decorated steps become attractive wells. From the coverage dependence the
      integrated CO well potential can be quantified. It is U(CO)a = -2.9 eV A on both
      Cu(332) and Cu(221) surfaces. Density functional calculations reveal that this
      attractive potential is due to the very local charge transfer from the Cu step
      atom to the adsorbed molecule.

PMID- 12059399
TI  - Computational capacity of the universe.
AB  - All physical systems register and process information. The laws of physics
      determine the amount of information that a physical system can register (number
      of bits) and the number of elementary logic operations that a system can perform
      (number of ops). The Universe is a physical system. The amount of information
      that the Universe can register and the number of elementary operations that it
      can have performed over its history are calculated. The Universe can have
      performed 10(120) ops on 10(90) bits ( 10(120) bits including gravitational
      degrees of freedom).

PMID- 12059400
TI  - Interaction cost of nonlocal gates.
AB  - We introduce the interaction cost of a nonlocal gate as the minimal time of
      interaction required to perform the gate when assisting the process with fast
      local unitaries. This cost, of interest both in the areas of quantum control and
      quantum information, depends on the specific interaction, and allows one to
      compare in an operationally meaningful manner any two nonlocal gates. In the case
      of a two-qubit system, an analytical expression for the interaction cost of any
      unitary operation given any coupling Hamiltonian is obtained. One gate may be
      more time consuming than another for any possible interaction. This defines a
      partial order structure in the set of nonlocal gates, that compares their degree
      of nonlocality. We analytically characterize this partial order in a region of
      the set of two-qubit gates.

PMID- 12059397
TI  - X-ray magnetochiral dichroism: a new spectroscopic probe of parity nonconserving
      magnetic solids.
AB  - We report the first experimental detection of x-ray magnetochiral dichroism in
      magnetoelectric Cr2O3. This dichroism, which does not require any polarized x-ray
      beam, is related to the time-reversal odd part of the optical activity tensor
      dominated by electric dipole-electric quadrupole E1E2 interference terms. The
      experiments were carried out using either a single crystal or a powdered pellet
      required to grow a single antiferromagnetic domain by magnetoelectric annealing.
      This new element (edge) specific spectroscopy offers unique access to the atomic
      orbital anapole moment Omega-z.

PMID- 12059401
TI  - Formation and interaction of membrane tubes.
AB  - We show that the formation of membrane tubes (or membrane tethers), which is a
      crucial step in many biological processes, is highly nontrivial and involves
      first-order shape transitions. The force exerted by an emerging tube is a
      nonmonotonic function of its length. We point out that tubes attract each other,
      which eventually leads to their coalescence. We also show that detached tubes
      behave like semiflexible filaments with a rather short persistence length. We
      suggest that these properties play an important role in the formation and
      structure of tubular organelles.

PMID- 12059402
TI  - Collective dynamics of chaotic chemical oscillators and the law of large numbers.
AB  - Experiments on the nontrivial collective dynamics and phase synchronization of
      populations of nonidentical chaotic electrochemical oscillators are presented.
      Without added coupling no deviation from the law of large numbers is observed.
      Deviations do arise with weak global or short-range coupling; large, irregular,
      and periodic mean field oscillations occur along with (partial) phase
      synchronization.

PMID- 12059403
TI  - Quantitative electron holography of biased semiconductor devices.
AB  - Electron holography is used to measure electrostatic potential profiles across
      reverse-biased Si p-n junctions in situ in the transmission electron microscope.
      A novel sample geometry based on focused ion-beam milling is developed, and
      results are obtained for a range of sample thicknesses and bias voltages to allow
      the holographic contrast to be interpreted. The physical and electrical nature of
      the sample surface, which is affected by sample preparation and electron beam
      irradiation, is discussed.

PMID- 12059404
TI  - Foreshocks and aftershocks in the Olami-Feder-Christensen model.
AB  - With the help of numerical simulations we show that the established Olami-Feder
      Christensen earthquake model exhibits sequences of foreshocks and aftershocks;
      this behavior has not been recognized in previous studies. Our results are
      consistent with Omori's empirical law, but the exponents predicted by the model
      are lower than observed in nature. The occurrence of foreshocks and aftershocks
      can be attributed to the nonconservative character of the Olami-Feder-Christensen
      model.

PMID- 12059405
TI  - Network topology of a potential energy landscape: a static scale-free network.
AB  - Here we analyze the topology of the network formed by the minima and transition
      states on the potential energy landscape of small clusters. We find that this
      network has both a small-world and scale-free character. In contrast to other
      scale-free networks, where the topology results from the dynamics of the network
      growth, the potential energy landscape is a static entity. Therefore, a
      fundamentally different organizing principle underlies this behavior: The
      potential energy landscape is highly heterogeneous with the low-energy minima
      having large basins of attraction and acting as the highly connected hubs in the
      network.

PMID- 12059406
TI  - Self-segregation versus clustering in the evolutionary minority game.
AB  - Complex adaptive systems have been the subject of much recent attention. It is by
      now well established that members ("agents") tend to self-segregate into opposing
      groups characterized by extreme behavior. However, the study of such adaptive
      systems has mostly been restricted to simple situations in which the prize-to
      fine ratio R equals unity. In this Letter we explore the dynamics of evolving
      populations with various different values of the ratio R, and demonstrate that
      extreme behavior is in fact not a generic feature of adaptive systems. In
      particular, we show that "confusion" and "indecisiveness" take over in times of
      depression, in which case cautious agents perform better than extreme ones.

PMID- 12059407
TI  - Comment on "Anomalous stimulated Brillouin scattering via ultraslow light".

PMID- 12059409
TI  - Direct observation of the phonon energy in a Bose-Einstein condensate by
      tomographic imaging.
AB  - The momentum and energy of phonons in a Bose-Einstein condensate are measured
      directly from a time-of-flight image by computerized tomography. We find that the
      same atoms that carry the momentum of the excitation also carry the excitation
      energy. The measured energy is in agreement with the Bogoliubov spectrum.
      Hydrodynamic simulations are performed which confirm our observation.

PMID- 12059410
TI  - Statistics of magnetic noise in neutron star crusts.
AB  - The neutron star crust magnetodynamics is demonstrated to exhibit erratic jumps
      at the fields corresponding to a sharp change of nuclide magnetic moments induced
      by quantization effects. Such a noise originates from magnetic avalanches and
      shows intensity and statistical properties which are favorably compared to the
      burst activity of soft gamma repeaters.

PMID- 12059411
TI  - Testing the self-duality of topological lumps in SU(3) lattice gauge theory.
AB  - We discuss a simple formula which connects the field-strength tensor to a
      spectral sum over certain quadratic forms of the eigenvectors of the lattice
      Dirac operator. We analyze these terms for the near zero modes and find that they
      give rise to contributions which are essentially either self-dual or anti-self
      dual. Modes with larger eigenvalues in the bulk of the spectrum are more
      dominated by quantum fluctuations and are less (anti-)self-dual. In the high
      temperature phase of QCD we find considerably reduced (anti-)self-duality for the
      modes near the edge of the spectral gap.

PMID- 12059412
TI  - Black hole production and large extra dimensions.
AB  - Black hole (BH) production at colliders is possible when the colliding energy is
      above the Planck scale, which can effectively be at TeV scale in models of large
      extra dimensions. In this work, we study the production of black holes at
      colliders and discuss the possible signatures. We point out the " ij-->BH+others"
      subprocesses, in which the BH and other standard-model particles are produced
      with a large transverse momentum. When the BH decays, it gives a signature that
      consists of particles of high multiplicity in a boosted spherical shape on one
      side of the event and a few numbers of high p(T) partons on the other side, which
      provide very useful tags for the event.

PMID- 12059413
TI  - Increased yield of ttbb at Hadron Colliders in low-energy supersymmetry.
AB  - Light bottom squarks and gluinos have been invoked to explain the b quark pair
      production excess at the Fermilab Tevatron. We investigate the associated
      production of ttbb at hadron colliders in this scenario, and find that the rates
      for this process are enhanced over the standard model prediction. If light
      gluinos exist, it may be possible to detect them at the Tevatron, and they could
      easily be observed at the CERN Large Hadron Collider.

PMID- 12059416
TI  - Coulomb excitation of radioactive 132,134,136Te beams and the low B(E2) of 136Te.
AB  - The B(E2;0(+)-->2+) values for the first 2+ excited states of neutron-rich
      132,134,136Te have been measured using Coulomb excitation of radioactive ion
      beams. The B(E2) values obtained for 132,134Te are in excellent agreement with
      expectations based on the systematics of heavy stable Te isotopes, while that for
      136Te is unexpectedly small. These results are discussed in terms of proton
      neutron configuration mixing and shell-model calculations using realistic
      effective interactions.

PMID- 12059417
TI  - Strong, polarized Balmer-alpha fluorescence after resonant core excitation of
      HCl.
AB  - Visible-UV fluorescence has been analyzed after resonant Cl 2p core excitation of
      HCl molecules. The dispersed fluorescence spectra are dominated by emissions from
      atomic fragments. In particular, an intense and polarized Balmer H(alpha) line is
      observed after photoexcitation of the 2p(-1)nl Rydberg states. The excited
      hydrogen atoms are efficiently produced in the resonant Auger process and the
      subsequent dissociation of high lying HCl+ states. The experimental results,
      complemented by a time-resolved measurement of the H(alpha) decay, point to a
      universal mechanism for the production of H( n = 3) atoms in the dissociation of
      innershell excited HCl molecules.

PMID- 12059418
TI  - Raman coherence beats from entangled polarization eigenstates in InAs quantum
      dots.
AB  - The homodyne-detected transient four-wave-mixing response of InAs/GaAs self
      assembled quantum dots shows temporal oscillations of the optically induced Raman
      coherence arising from two entangled polarization eigenstates of the exciton. The
      phase sensitive nature of the homodyne detection enables us to follow the time
      evolution of the nonradiative quantum coherence between the polarization states,
      providing a measurement of the fine-structure splitting in the dots, which is
      much less than the inhomogeneous broadening, and the corresponding decoherence
      rate of the entangled state.

PMID- 12059419
TI  - Finite thermal conductivity in 1D models having zero Lyapunov exponents.
AB  - Heat conduction in three types of 1D channels is studied. The channels consist of
      two parallel walls, right triangles as scattering obstacles, and noninteracting
      particles. The triangles are placed along the walls in three different ways: (i)
      periodic, (ii) disordered in height, and (iii) disordered in position. The
      Lyapunov exponents in all three models are zero because of the flatness of
      triangle sides. It is found numerically that the temperature gradient can be
      formed in all three channels, but the Fourier heat law is observed only in two
      disordered ones. The results show that there might be no direct connection
      between chaos (in the sense of positive Lyapunov exponent) and normal thermal
      conduction.

PMID- 12059420
TI  - Slow relaxation, confinement, and solitons.
AB  - Millisecond crystal relaxation has been used to explain anomalous decay in doped
      alkali halides. We attribute this slowness to Fermi-Pasta-Ulam solitons. Our
      model exhibits confinement of mechanical energy released by excitation. Extending
      the model to long times is justified by its relation to solitons, excitations
      previously proposed to occur in alkali halides. Soliton damping and observation
      are also discussed.

PMID- 12059421
TI  - Formation of a spiraling line defect and its meandering transition in a period-2
      medium.
AB  - The instability of a period-1 spiral wave resulting in a period-2 spiral wave
      with a line defect is investigated for the first time in a laboratory system. At
      the very onset the transition proceeds by an emergence of a spiraling line
      defect, "breathing" intermittently while retaining its symmetry of a period-1
      spiral wave. With a further change in a control parameter, the line defect
      undergoes a meandering transition producing a compound tip trajectory, following
      a dynamic shape transition. The observed transitions have a strong analogy to the
      phase synchronization transition of two coupled nonlinear oscillators and the
      meandering transition of a period-1 spiral wave.

PMID- 12059422
TI  - Multifractal properties of return time statistics.
AB  - The global statistics of the return times of a dynamical system can be described
      by a new spectrum of generalized dimensions. Comparison with the usual
      multifractal analysis of measures is presented, and the difference between the
      two corresponding sets of dimensions is established. Theoretical analysis and
      numerical examples of dynamical systems in the class of iterated functions are
      presented.

PMID- 12059423
TI  - Caging of particles in one-component plasmas.
AB  - Strongly coupled Coulomb systems are characterized by localization ("caging") of
      particles trapped and oscillating in slowly fluctuating local potential wells.
      This observation constitutes the basic assumption underlying the quasilocalized
      charge approximation. Using molecular dynamics simulation we study the changes in
      the particles' surroundings (cages) in a classical three-dimensional one
      component plasma. The results of our analysis show that at high coupling values,
      substantial changes occur only after several plasma oscillation cycles. We also
      analyze the oscillation frequencies of the caged particles and relate the
      decorrelation of the cages to the process of self-diffusion.

PMID- 12059424
TI  - Intermittency in drift-wave turbulence: structure of the momentum flux
      probability distribution function.
AB  - We analytically compute the probability distribution function (PDF) of the local
      Reynolds stress ( R) for forced Hasegawa-Mima turbulence. With the assumption
      that the PDF tail is due to an instanton with the spatial form given by the modon
      solution, the tail of the PDF of R is found to be a stretched, non-Gaussian
      exponential, with the specific form exp[-cR(3/2)] ( c is a constant). We relate
      the temporal localization of the instanton to the degree of "burstiness" of the
      momentum transport event.

PMID- 12059425
TI  - Collective effects in grain boundary migration.
AB  - In situ high-resolution transmission electron microscopy is used to study grain
      boundary structure and kinetics in bicrystalline Au films at elevated
      temperature. We report the first direct evidence for the existence of cooperative
      atomic motion in grain boundary migration. Certain nanoregions at grain
      boundaries, typically involving up to several hundred atoms, are found to switch
      back and forth between neighboring grains. Reversible structural fluctuations at
      temperatures near 0.5T(m) and above have been discovered in [110] and [001] tilt,
      as well as in general grain boundaries.

PMID- 12059426
TI  - Evidence of fano-like interference phenomena in locally resonant materials.
AB  - Sonic crystals consisting of three-dimensional arrays of units which exhibit
      localized resonances have been discovered recently. Here, it is shown that their
      two-dimensional counterparts behave in a similar manner. Particularly, it is
      observed that the transmittance spectra show very asymmetric peaks which are
      explained as a Fano-like interference phenomenon. A finite difference time domain
      method is employed to perform a comprehensive study of the resonance line shape
      as a function of the mass density of the structural units. Also, a simple
      analytical model is introduced to give an intuitive account of the origin of the
      interference phenomenon.

PMID- 12059427
TI  - Structures of high and low density amorphous ice by neutron diffraction.
AB  - Neutron diffraction with isotope substitution is used to determine the structures
      of high (HDA) and low (LDA) density amorphous ice. Both "phases" are fully
      hydrogen bonded, tetrahedral networks, with local order similarities between LDA
      and ice Ih, and HDA and liquid water. Moving from HDA, through liquid water and
      LDA to ice Ih, the second shell radial order increases at the expense of spatial
      order. This is linked to a fifth first neighbor "interstitial" that restricts the
      orientations of first shell waters. This "lynch pin" molecule which keeps the HDA
      structure intact has implications for the nature of the HDA-LDA transition that
      bear on the current metastable water debate.

PMID- 12059428
TI  - Memory effect on the glass transition in vulcanized rubber.
AB  - The memory effect upon glassification is studied in the glass-to-rubber
      transition of vulcanized rubber with the strain as a controlling parameter. A
      phenomenological model is proposed, taking the history of the temperature and the
      strain into account, by which the experimental results are interpreted. The data
      and the model demonstrate that the glassy state memorizes the time course of
      strain upon glassification, not as a single parameter but as the history itself.
      The data also show that the effect of irreversible deformation in the glassy
      state is beyond the scope of the present model.

PMID- 12059429
TI  - Potential energy landscape equation of state.
AB  - Depth, number, and shape of the basins of the potential energy landscape are the
      key ingredients of the inherent structure thermodynamic formalism introduced by
      Stillinger and Weber [F. H. Stillinger and T. A. Weber, Phys. Rev. A 25, 978
      (1982)]. Within this formalism, an equation of state based only on the volume
      dependence of these landscape properties is derived. Vibrational and
      configurational contributions to pressure are sorted out in a transparent way.
      Predictions are successfully compared with data from extensive molecular dynamics
      simulations of a simple model for the fragile liquid orthoterphenyl.

PMID- 12059430
TI  - Fluctuation-dissipation relations in the activated regime of simple strong-glass
      models.
AB  - We study the out-of-equilibrium fluctuation-dissipation (FD) relations in the low
      temperature, finite-time, physical-aging regime of two simple models with strong
      glass behavior, the Fredrickson-Andersen model and the square-plaquette
      interaction model. We explicitly show the existence of unique, waiting-time
      independent dynamical FD relations. While in the Fredrickson-Andersen model the
      FD theorem is obeyed at all times, the plaquette model displays piecewise-linear
      FD relations, similar to what is found in disordered mean-field models and in
      simulations of supercooled liquids, and despite the fact that its static
      properties are trivial. We discuss the wider implications of these results.

PMID- 12059431
TI  - Stability of a flexible polar ionic crystal surface: metastable alumina and one
      dimensional surface metallicity.
AB  - A first-principles study of kappa-Al2O3 (001) and (001-) reveals new features of
      ion-surface stability and electronic structure. The need to generalize Tasker's
      rules for surface stability of low-symmetry crystals is shown. Structurally, the
      presence of bulk tetrahedral Al ( Al(T)) causes giant surface relaxations, with O
      termination at (001). Surface-layer Al(T) are strongly unfavored. This is
      understood with Pauling's rules and thus generally applicable to metastable
      aluminas. The bulk charge asymmetry and Al-sublattice anisotropy caused by the
      Al(T) create a 1D metallic surface state at (001-).

PMID- 12059432
TI  - Novel sb induced reconstruction of the (113) surface of ge.
AB  - Sb induces on Ge(113) a c(2 x 2) reconstruction in which Sb breaks one Ge-Ge bond
      and occupies an interstitial site, in contrast to Sb adsorption on other Si or Ge
      surfaces. Sb saturates the three dangling bonds per unit cell of the (113)
      surface inducing a large strain which is released by occupation of the
      interstitial site. Two neighboring Sb at interstitial sites form a dimer. The
      structure has been determined by x-ray diffraction, applying direct methods, and
      ab initio density-functional-theory calculations. The adsorption geometry and the
      high binding energy lead one to expect that Sb cannot be used as a surfactant for
      the growth of Si/Ge layers on the (113) surface.

PMID- 12059414
TI  - Measurement of B0-B-0 flavor oscillations in hadronic B0 decays.
AB  - Flavor oscillations of neutral B mesons have been studied in e+e- annihilation
      data collected with the BABAR detector at center-of-mass energies near the
      upsilon(4S) resonance. The data sample used for this purpose consists of events
      in which one B0 meson is reconstructed in a hadronic decay mode, while the flavor
      of the recoiling B0 is determined with a tagging algorithm that exploits the
      correlation between the flavor of the heavy quark and the charges of its decay
      products. From the time development of the observed mixed and unmixed final
      states, we determine the B0-B-0 oscillation frequency deltamd to be 0.516+/
      0.016(stat)+/-0.010(syst) ps-1.

PMID- 12059434
TI  - Stress relief as the driving force for self-assembled bi nanolines.
AB  - Bi nanolines self-assemble on Si(001) and are remarkable for their straightness
      and length-they are often more than 400 nm long, and a kink in a nanoline has
      never been observed. Through electronic structure calculations, we have found an
      energetically favorable structure for these nanolines that agrees with our
      scanning tunneling microscopy and photoemission experiments; the structure has an
      extremely unusual subsurface structure, comprising a double core of seven
      membered rings of silicon. Our proposed structure explains all the observed
      features of the nanolines, and shows that surface stress resulting from the
      mismatch between the Bi and the Si substrates is responsible for their self
      assembly. This has wider implications for the controlled growth of nanostructures
      on semiconductor surfaces.

PMID- 12059433
TI  - Material anisotropy revealed by phase contrast in intermittent contact atomic
      force microscopy.
AB  - Phase contrast in intermittent-contact atomic force microscopy (AFM) reveals in
      plane structural and mechanical properties of polymer monolayers. This is
      surprising, because measurements of nanoscale in-plane properties typically
      require contact mode microscopies. Our measurements are possible because the tip
      oscillates not just perpendicular but also parallel to the sample surface along
      the long axis of the cantilever. This lateral tip displacement is virtually
      universal in AFM, implying that any oscillating-tip AFM technique is sensitive to
      in-plane material properties.

PMID- 12059435
TI  - Surface diffusion anomaly near a substrate phase transition: H on W(100).
AB  - Using a linear optical diffraction method, we have experimentally studied the
      long predicted diffusion anomalous behavior for H/W(100) near the reconstructive
      phase transition of the W(100) substrate. This anomaly manifests itself in the
      form of a strong dip in the diffusion coefficient D at the transition temperature
      T(C). We interpret the strong reduction of D as a result of the diverging
      friction damping near the transition. The finite dip in D instead of a vanishing
      D at T(C) also demonstrates the importance of the non-Markovian (memory)
      deviation from the simple instantaneous damping picture.

PMID- 12059436
TI  - Photoinduced quantum interference antiresonances in pi-conjugated polymers.
AB  - We observed photoinduced quantum interference antiresonances between several
      discrete infrared-active vibrations and the lower-polaron continuous absorption
      band in a series of pi-conjugated polymer films having superior planar orders,
      where the polaron transition energy is relatively small. The photoinduced Fano
      type antiresonances are well explained by extending the amplitude mode model
      beyond the adiabatic limit. The agreement between the data and the model confirms
      the presence of a continuous electronic band above the polaron state. We show
      that high frequency modes are strongly coupled to electrons, with implications
      for superconductivity.

PMID- 12059437
TI  - Electron-hole coupling and the charge density wave transition in TiSe2.
AB  - Angle-resolved photoemission is employed to measure the band structure of TiSe2
      in order to clarify the nature of the ( 2 x 2 x 2) charge density wave
      transition. The results show a very small indirect gap in the normal phase
      transforming into a larger indirect gap at a different location in the Brillouin
      zone. Fermi surface topology is irrelevant in this case. Instead, electron-hole
      coupling together with a novel indirect Jahn-Teller effect drives the transition.

PMID- 12059438
TI  - Singular effects of impurities near the ferromagnetic quantum-critical point.
AB  - Systematic theoretical results for the effects of a dilute concentration of
      magnetic impurities on the thermodynamic and transport properties in the region
      around the quantum critical point of a ferromagnetic transition are obtained. In
      the quasiclassical regime, the dynamical spin fluctuations enhance the Kondo
      temperature. This energy scale decreases rapidly in the quantum fluctuation
      regime, where the properties are those of a line of critical points of the
      multichannel Kondo problem with the number of channels increasing as the critical
      point is approached, except at unattainably low temperatures where a single
      channel wins out.

PMID- 12059439
TI  - Occupation of a resonant level coupled to a chiral Luttinger liquid.
AB  - We consider a resonant level coupled to a chiral Luttinger liquid which can be
      realized, e.g., at a fractional quantum Hall edge. We study the dependence of the
      occupation probability n of the level on its energy epsilon for various values of
      the Luttinger-liquid parameter g. At g<1/2, a weakly coupled level shows a sharp
      jump in n(epsilon) at the Fermi level. As the coupling is increased, the
      magnitude of the jump decreases until sqrt[2g], and then the discontinuity in
      n(epsilon) disappears. We show that n(epsilon) can be expressed in terms of the
      magnetization of a Kondo impurity as a function of magnetic field.

PMID- 12059440
TI  - Many-body approach to spin-dependent transport in quantum dot systems.
AB  - By means of a diagram technique for Hubbard operators, we show the existence of a
      spin-dependent renormalization of the localized levels in an interacting region,
      e.g., quantum dot, modeled by the Anderson Hamiltonian with two conduction bands.
      It is shown that the renormalization of the levels with a given spin direction is
      due to kinematic interactions with the conduction subbands of the opposite spin.
      The consequence of this dressing of the localized levels is a drastically
      decreased tunneling current for ferromagnetically ordered leads compared to that
      of paramagnetically ordered leads. Furthermore, the studied system shows a spin
      dependent resonant tunneling behavior for ferromagnetically ordered leads.

PMID- 12059441
TI  - Conductance of small molecular junctions.
AB  - A new method of fabricating small metal-molecule-metal junctions is developed,
      approaching the single-molecule limit. The conductance of different conjugated
      molecules in a broad temperature, source-drain, and gate voltage regime is
      reported. At low temperature, all investigated molecules display sharp
      conductance steps periodic in source-drain voltage. The position of these steps
      can be controlled by a gate potential. The spacing corresponds to the energy of
      the lowest molecular vibrations. These results show that the low-bias conductance
      of molecules is dominated by resonant tunneling through coupled electronic and
      vibration levels.

PMID- 12059442
TI  - Finite-size effects in the conductivity of cluster assembled nanostructures.
AB  - Atomic clusters have been deposited between lithographically defined contacts
      with nanometer scale separations. The design of the contacts is based on an
      appropriate application of percolation theory to conduction in cluster deposited
      devices and allows finite-size effects to be clearly observed. It is
      demonstrated, both by experiment and by simulation, that for small contact
      separations the percolation threshold is shifted to extremely low surface
      coverages. The selected rectangular contact geometry ensures that wirelike
      structures are formed close to the percolation threshold.

PMID- 12059443
TI  - Intersubband transport in quantum wells in strong magnetic fields mediated by
      single- and two-electron scattering.
AB  - We show theoretically that in quantum wells subjected to a strong magnetic field
      the intersubband current peaks at magnetic field values, which reveal the
      underlying specific intersubband scattering mechanism. We have designed and grown
      a superlattice structure in which such current oscillations are clearly visible,
      and in which the transition from the purely single-electron to the mixed single-
      and two-electron scattering regimes can be observed by tuning the applied voltage
      bias. The measurements were conducted in ultrahigh magnetic fields (up to 45 T)
      to obtain the full spectrum of the current oscillations.

PMID- 12059415
TI  - Measurement of the B0-B-0 oscillation frequency with inclusive dilepton events.
AB  - The B0-B-0 oscillation frequency has been measured with a sample of 23 x 10(6) BB
      pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at
      SLAC. In this sample, we select events in which both B mesons decay
      semileptonically and use the charge of the leptons to identify the flavor of each
      B meson. A simultaneous fit to the decay time difference distributions for
      opposite- and same-sign dilepton events gives deltamd = 0.493+/-0.012(stat)+/
      0.009(syst) ps-1.

PMID- 12059444
TI  - Two-electron quantum dot molecule: composite particles and the spin phase
      diagram.
AB  - We study a two-electron quantum dot molecule in a magnetic field by the direct
      diagonalization of the Hamiltonian matrix. The ground states of the molecule with
      the total spin S = 0 and S = 1 provide a possible realization for a qubit of a
      quantum computer. Switching between the states is best achieved by changing the
      magnetic field. Based on an analysis of the wave function, we show that the
      system consists of composite particles formed by an electron and flux quanta
      attached to it. This picture can also be used to explain the spin phase diagram.

PMID- 12059445
TI  - Low-temperature fate of the 0.7 structure in a point contact: a Kondo-like
      correlated state in an open system.
AB  - Besides the usual conductance plateaus at multiples of 2e(2)/h, quantum point
      contacts typically show an extra plateau at approximately 0.7(2e(2)/h), believed
      to arise from electron-electron interactions that prohibit the two spin channels
      from being simultaneously occupied. We present evidence that the disappearance of
      the 0.7 structure at very low temperature signals the formation of a Kondo-like
      correlated spin state. Evidence includes a zero-bias conductance peak that splits
      in a parallel field, scaling of conductance to a modified Kondo form, and
      consistency between peak width and the Kondo temperature.

PMID- 12059447
TI  - Strongly correlated s-wave superconductivity in the N-type infinite-layer
      cuprate.
AB  - Quasiparticle tunneling spectra of the electron-doped ( n-type) infinite-layer
      cuprate Sr0.9La0.1CuO2 reveal characteristics that counter a number of common
      phenomena in the hole-doped ( p-type) cuprates. The optimally doped
      Sr0.9La0.1CuO2 with T(c) = 43 K exhibits a momentum-independent superconducting
      gap Delta = 13.0+/-1.0 meV that substantially exceeds the BCS value, and the
      spectral characteristics indicate insignificant quasiparticle damping by spin
      fluctuations and the absence of pseudogap. The response to quantum impurities in
      the Cu sites also differs fundamentally from that of the p-type cuprates with
      d(x(2)-y(2))-wave pairing symmetry.

PMID- 12059446
TI  - New superconducting phases in field-induced organic superconductor lambda
      (BETS)2FeCl4.
AB  - We derive the parallel upper critical field, Hc2, as a function of the
      temperature T in quasi-2D organic compound lambda-(BETS)2FeCl4, accounting for
      the formation of the nonuniform Larkin-Ovchinnikov-Fulde-Ferrell (LOFF) state. To
      further check the 2D LOFF model, we propose to study the Hc2(T) curve at low T in
      tilted fields, where the vortex state is described by the high Landau level
      functions characterized by the index n. We predict a cascade of first-order
      transitions between vortex phases with different n, between phases with different
      types of the symmetry at given n and the change of the superconducting transition
      from the second order to the first order as FeCl4 ions are replaced partly by
      GaCl4 ions.

PMID- 12059448
TI  - Duality between unidirectional harge-density-wave order and superconductivity.
AB  - The existence of a duality between a unidirectional charge-density-wave order and
      a superconducting order is shown. This duality predicts the existence of a charge
      density wave near a superconducting vortex, and the existence of
      superconductivity near a charge-density-wave dislocation.

PMID- 12059449
TI  - Universal heat transport in Sr2RuO4.
AB  - We present the temperature dependence of the thermal conductivity kappa(T) of the
      unconventional superconductor Sr2RuO4 down to low temperatures ( approximately
      100 mK). In the T-->0 K limit we found a finite residual term in kappa/T,
      providing clear evidence for the superconducting state with an unconventional
      pairing. The residual term remains unchanged for samples with different T(c),
      demonstrating the universal character of heat transport in this spin-triplet
      superconductor. The low-temperature behavior of kappa suggests the strong
      impurity scattering with a phase shift close to pi/2. A criterion for the
      observation of universality is experimentally deduced.

PMID- 12059450
TI  - Pairing of Cooper pairs in a fully frustrated Josephson-junction chain.
AB  - We study a one-dimensional Josephson-junction chain embedded in a magnetic field.
      We show that, when the magnetic flux per elementary loop equals half the
      superconducting flux quantum phi0 = h/2e, a local Z2 symmetry arises. This
      symmetry is responsible for a nematic Luttinger liquid state associated with
      bound states of Cooper pairs. We analyze the phase diagram and discuss some
      experimental possibilities to observe this exotic phase.

PMID- 12059451
TI  - All-optical probe of coherent spin waves.
AB  - A novel, all-optical method to excite and detect spin waves in magnetic materials
      is presented. By exploiting the temperature dependence of the magnetic
      anisotropy, an ultrashort laser pulse is efficiently converted in a picosecond
      "anisotropy field" pulse that triggers a coherent precession of the
      magnetization. Recording the temporal evolution of the precessing spins by a time
      delayed probe-pulse provides a quantitative method to study locally the magnetic
      anisotropy, as well as switching and damping phenomena in micromagnetic
      structures. Applications to nickel and permalloy ( Ni80Fe20) films are discussed,
      particularly showing the possibility to explore standing spin waves in thin
      films.

PMID- 12059452
TI  - Deep inelastic atomic scattering of x rays in liquid neon.
AB  - An inelastic x-ray scattering (IXS) experiment in liquid neon has been performed
      in the +/-100 meV exchanged energy range and at exchanged wave numbers, q,
      comprised between 1 and 16 A(-1). At the highest probed q's a deep inelastic
      scattering regime is reached where the Ne core electrons, after collision with
      the x rays, recoil almost freely with an effective mass equal to the Ne atomic
      mass. IXS in this high q regime is here shown to provide quantitative information
      on the atomic momentum distribution of liquid Ne, thus supplying a complementary
      technique to neutron scattering. There are several open problems in quantum and
      classical liquids which can benefit from this complementarity.

PMID- 12059453
TI  - Relationship between measures of fitness and time scale in evolution.
AB  - The notion of fitness is central in evolutionary biology. We use a simple
      spatially extended predator-prey or host-pathogen model to show a generic case
      where the average number of offspring of an individual as a measure of fitness
      fails to characterize the evolutionary dynamics. Mutants with high initial
      reproduction ratios have lineages that eventually go extinct due to local
      overexploitation. We propose general quantitative measures of fitness that
      reflect the importance of time scale in evolutionary processes.

PMID- 12059454
TI  - Robust patterns in food web structure.
AB  - We analyze the properties of seven community food webs from a variety of
      environments, including freshwater, marine-freshwater interfaces, and terrestrial
      environments. We uncover quantitative unifying patterns that describe the
      properties of the diverse trophic webs considered and suggest that statistical
      physics concepts such as scaling and universality may be useful in the
      description of ecosystems. Specifically, we find that several quantities
      characterizing these diverse food webs obey functional forms that are universal
      across the different environments considered. The empirical results are in
      remarkable agreement with the analytical solution of a recently proposed model
      for food webs.

PMID- 12059455
TI  - Effect of internal friction on biofilament dynamics.
AB  - We consider biofilaments-flexible multimolecule structures common in cell biology
      and show how "internal" friction associated with either conformational
      fluctuations or with fluid flow through narrow pores inside the filaments can
      dominate the external hydrodynamic friction usually considered to be the main
      energy dissipation process. The signature of this is wave-number-independent
      relaxation time of bending fluctuations. Preliminary experimental data for
      bending fluctuations of single folded (mitotic) chromosomes display these
      dynamics.

PMID- 12059456
TI  - Adaptive sampling by information maximization.
AB  - The investigation of input-output systems often requires a sophisticated choice
      of test inputs to make the best use of limited experimental time. Here we present
      an iterative algorithm that continuously adjusts an ensemble of test inputs on
      line, subject to the data already acquired about the system under study. The
      algorithm focuses the input ensemble by maximizing the mutual information between
      input and output. We apply the algorithm to simulated neurophysiological
      experiments and show that it serves to extract the ensemble of stimuli that a
      given neural system "expects" as a result of its natural history.

PMID- 12059457
TI  - Nonconservative earthquake model of self-organized criticality on a random graph.
AB  - We numerically investigate the Olami-Feder-Christensen model on a quenched random
      graph. Contrary to the case of annealed random neighbors, we find that the
      quenched model exhibits self-organized criticality deep within the
      nonconservative regime. The probability distribution for avalanche size obeys
      finite size scaling, with universal critical exponents. In addition, a power law
      relation between the size and the duration of an avalanche exists. We propose
      that this may represent the correct mean-field limit of the model rather than the
      annealed random neighbor version.

PMID- 12059458
TI  - Excitable front geometry in reaction-diffusion systems with anomalous dispersion.
AB  - Two-dimensional excitable systems with anomalous dispersion provide a discrete
      set of interpulse distances for the stable propagation of planar wave trains.
      Numerical simulations show that the trailing front of a pulse pair can undergo
      transitions between these stable distances. In response to localized
      perturbations, the trailing front converges towards one of numerous, sigmoidal
      shapes. Their transition segments move at constant speeds and can collide and
      fuse with each other. A complementing kinematic analysis of the front dynamics
      yields a reaction-diffusion-like equation.

PMID- 12059459
TI  - Electromechanical noise in a diffusive conductor.
AB  - Electrons moving in a conductor can transfer momentum to the lattice via
      collisions with impurities and boundaries, giving rise to a fluctuating
      mechanical stress tensor. The root-mean-squared momentum transfer per scattering
      event in a disordered metal (of dimension L greater than the mean-free path l and
      screening length xi) is found to be reduced below the Fermi momentum by a factor
      of order l/L for shear fluctuations and (xi/L)(2) for pressure fluctuations. The
      excitation of an elastic bending mode by the shear fluctuations is estimated to
      fall within current experimental sensitivity for a nanomechanical oscillator.

PMID- 12059460
TI  - Decoherence and 1/f noise in Josephson qubits.
AB  - We propose and study a model of dephasing due to an environment of bistable
      fluctuators. We apply our analysis to the decoherence of Josephson qubits,
      induced by background charges present in the substrate, which are also
      responsible for the 1/f noise. The discrete nature of the environment leads to a
      number of new features which are mostly pronounced for slowly moving charges. Far
      away from the degeneracy this model for the dephasing is solved exactly.

PMID- 12059461
TI  - Molecular wires acting as coherent quantum ratchets.
AB  - The effect of laser fields on electron transport through a molecular wire weakly
      coupled to two leads is investigated. The molecular wire acts as a coherent
      quantum ratchet if the molecule is composed of periodically arranged, asymmetric
      chemical groups. This setup presents a quantum rectifier with a finite dc
      response in the absence of a static bias. The nonlinear current is evaluated in
      closed form within the Floquet basis of the isolated, driven wire. The current
      response reveals multiple current reversals together with a nonlinear dependence
      on the amplitude and the frequency of the laser field. The current saturates for
      long wires at a nonzero value, while it may change sign upon decreasing its
      length.

PMID- 12059462
TI  - Semiclassical balance equations in semiconductor superlattices in strong crossed
      fields.

PMID- 12059464
TI  - Bell's theorem for general N-qubit states.
AB  - We derive a single general Bell inequality which is a sufficient and necessary
      condition for the correlation function for N particles to be describable in a
      local and realistic picture, for the case in which measurements on each particle
      can be chosen between two arbitrary dichotomic observables. We also derive a
      necessary and sufficient condition for an arbitrary N-qubit mixed state to
      violate this inequality. This condition is a generalization and reformulation of
      the Horodecki family condition for two qubits.

PMID- 12059465
TI  - Do all pure entangled states violate Bell's inequalities for correlation
      functions?
AB  - Any pure entangled state of two particles violates a Bell inequality for two
      particle correlation functions (Gisin's theorem). We show that there exist pure
      entangled N>2 qubit states that do not violate any Bell inequality for N particle
      correlation functions for experiments involving two dichotomic observables per
      local measuring station. We also find that Mermin-Ardehali-Belinskii-Klyshko
      inequalities may not always be optimal for refutation of local realistic
      description.

PMID- 12059467
TI  - Real-time Bose-Einstein condensation in a finite volume with a discrete spectrum.
AB  - We show that Bose condensation in real time occurs in a finite system not only as
      an accumulation of the bosons in the ground state below a critical temperature,
      but also as a rapid enhancement of an arbitrary small symmetry breaking, followed
      by a very slow decay of the symmetry breaking order parameter from the almost
      ideal value to the vanishing equilibrium value. We show this analytically on an
      exactly soluble model and numerically on a model of noninteracting bosons in an
      oscillator potential.

PMID- 12059466
TI  - Cold bose gases with large scattering lengths.
AB  - We calculate the energy and condensate fraction for a dense system of bosons
      interacting through an attractive short range interaction with positive s-wave
      scattering length a. At high densities n>>a(-3), the energy per particle,
      chemical potential, and square of the sound speed are independent of the
      scattering length and proportional to n(2/3), as in Fermi systems. The condensate
      is quenched at densities na(3) approximately 1.

PMID- 12059468
TI  - Classical no-cloning theorem.
AB  - A classical version of the no-cloning theorem is discussed. We show that an
      arbitrary probability distribution associated with a (source) system cannot be
      copied onto another (target) system while leaving the original distribution of
      the source system unperturbed. For classical dynamical systems such a perfect
      cloning process is not permitted by the Liouvillian (ensemble) evolution
      associated with the joint probability distribution of the composite source-target
      copying machine system.

PMID- 12059469
TI  - The fields of uniformly accelerated charges in de Sitter spacetime.
AB  - The scalar and electromagnetic fields of charges uniformly accelerated in de
      Sitter spacetime are constructed. They represent the generalization of the Born
      solutions describing fields of two particles with hyperbolic motion in flat
      spacetime. In the limit Lambda-->0, the Born solutions are retrieved. Since in
      the de Sitter universe the infinities I+/- are spacelike, the radiative
      properties of the fields depend on the way in which a given point of I+/- is
      approached. The fields must involve both retarded and advanced effects: Purely
      retarded fields do not satisfy the constraints at the past infinity I-.

PMID- 12059470
TI  - Nonlinear kinetic Sunyaev-Zeldovich effect.
AB  - We derive fully nonlinear expressions for temperature fluctuations from the
      kinetic Sunyaev-Zeldovich (SZ) effect, the scattering of cosmic microwave
      background photons off hot electrons in bulk motion. Our result reproduces the
      Ostriker-Vishniac effect to second order in perturbation theory but contains
      nonlinear corrections to the electron velocities and densities that were
      neglected previously. We use the recently developed halo model for nonlinear
      gravitational clustering to compute the nonlinear kinetic SZ power spectrum,
      which dominates the primary anisotropy on small angular scales.

PMID- 12059471
TI  - Correlated perturbations from inflation and the cosmic microwave background.
AB  - We compare the latest cosmic microwave background data with theoretical
      predictions including correlated adiabatic and cold dark matter (CDM)
      isocurvature perturbations with a simple power-law dependence. We find that there
      is a degeneracy between the amplitude of correlated isocurvature perturbations
      and the spectral tilt. A negative (red) tilt is found to be compatible with a
      larger isocurvature contribution. Estimates of the baryon and CDM densities are
      found to be almost independent of the isocurvature amplitude. The main result is
      that current microwave background data do not exclude a dominant contribution
      from CDM isocurvature fluctuations on large scales.

PMID- 12059472
TI  - Statistical interpretation of the Bekenstein entropy for systems with a stretched
      horizon.
AB  - For the two-charge extremal holes in string theory we show that the Bekenstein
      entropy obtained from the area of the stretched horizon has a statistical
      interpretation as a "coarse graining entropy": different microstates give
      geometries that differ near r = 0, and the stretched horizon cuts off the metric
      at r = b where these geometries start to differ.

PMID- 12059473
TI  - Is the unitarity of the quark-mixing CKM matrix violated in neutron beta-decay?
AB  - We report on a new measurement of neutron beta-decay asymmetry. From the result
      A(0) = -0.1189(7), we derive the ratio of the axial vector to the vector coupling
      constant lambda = g(A)/g(V) = -1.2739(19). When included in the world average for
      the neutron lifetime tau = 885.7(7) s, this gives the first element of the
      Cabibbo-Kobayashi-Maskawa (CKM) matrix V(ud). With this value and the Particle
      Data Group values for V(us) and V(ub), we find a deviation from the unitarity
      condition for the first row of the CKM matrix of Delta = 0.0083(28), which is 3.0
      times the stated error.

PMID- 12059475
TI  - Ab initio molecular dynamics for molecules with variable numbers of electrons.
AB  - The ab initio molecular dynamics method is extended to treat exchange of
      electrons between molecules and a reservoir at fixed chemical potential. The
      method is based on a rigorously grand-canonical density functional approach using
      separate potential energy surfaces for each oxidation state. It is shown that the
      resulting discontinuous dependency of excess charge on chemical potential is
      consistent with the statistical thermodynamics of equilibrium gas-phase
      reactions. The method is illustrated by an application to the adiabatic redox
      dynamics of an aniline molecule.

PMID- 12059474
TI  - Delay-dependent amplification of a probe pulse via stimulated Rayleigh
      scattering.
AB  - Stimulated Rayleigh scattering of pump and probe light pulses of close carrier
      frequencies is considered. A nonzero time delay between the two pulses is shown
      to give rise to amplification of the delayed (probe) pulse accompanied by
      attenuation of the pump, both on resonance and off resonance. In either case,
      phase-matching effects are shown to provide a sufficiently large gain, which can
      exceed significantly direct one-photon absorption losses.

PMID- 12059476
TI  - Population inversion induced by collisions in a two level system under
      nonresonance optical excitation.
AB  - When the gas particles, which can be considered as a two level quantum system,
      are affected by frequent collisions with buffer gas particles (thermal
      reservoir), the spectral densities of the Einstein coefficients for absorption
      and induced emission are unequal to each other far from the absorption (emission)
      line. The relationship between the spectral densities at the specified condition
      reveals new physical phenomena. The mostly convincing example is the fact that
      population inversion is established in a two level system under nonresonance
      optical excitation. This effect is experimentally observed as a lasing on sodium
      resonance transitions.

PMID- 12059477
TI  - Reynolds number dependence of streamwise velocity spectra in turbulent pipe flow.
AB  - Spectra of the streamwise velocity component in fully developed turbulent pipe
      flow are presented for Reynolds numbers up to 5.7x10(6). Even at the highest
      Reynolds number, streamwise velocity spectra exhibit incomplete similarity only:
      while spectra collapse with both classical inner and outer scaling for limited
      ranges of wave number, these ranges do not overlap. Thus similarity may not be
      described as complete, and a region varying with the inverse of the streamwise
      wave number, k(1), is not expected, and any apparent k(-1)(1) range does not
      attract any special significance and does not involve a universal constant.
      Reasons for this are suggested.

PMID- 12059478
TI  - Combined pressure and electrical-resistivity measurements of warm dense aluminum
      and titanium plasmas.
AB  - Electrical resistivity, pressure, and internal energy variation of warm dense
      correlated titanium (density 0.2 g/cm(3)) and aluminum (density 0.1 g/cm(3))
      plasmas are measured using a homogeneous and thermally equilibrated media
      produced inside an isochoric closed-vessel plasma. These data are compared to
      detailed calculations based on the density functional theory. In the studied
      temperature range (15,000-30,000 K), it appears that both exchange-correlation
      and ion-ion interaction treatments are of great importance to calculate accurate
      theoretical values.

PMID- 12059479
TI  - Nonlinear compressional pulses in a 2D crystallized dusty plasma.
AB  - Compressional pulses were launched in a two-dimensional Yukawa lattice, a
      hexagonal monolayer of polymer microspheres suspended in a plasma. The pulsed
      wave was excited by a laser beam, and nonlinear effects were observed for Mach
      numbers M>0.07 and for variation of particle number density delta(n)/n>0.1, but
      no steepening of the pulse was detected. The pulse propagation speed was found to
      be comparable to the sound speed of compressional waves launched with sinusoidal
      excitation.

PMID- 12059480
TI  - Magnetic reconnection in the two-dimensional Kelvin-Helmholtz instability.
AB  - Magnetic reconnection in the two-dimensional Kelvin-Helmholtz instability is
      studied. The flow is modeled by the reduced MHD equations with constant
      resistivity and viscosity. For super-Alfvenic flow, localized transient
      reconnection is observed on the Kelvin-Helmholtz time scale (this is not new). We
      study this transient reconnection and consider the peak reconnection rate which
      occurs with the initial vortex formation. Over the range of resistivities
      considered, it is shown that this peak reconnection rate is not a function of
      resistivity, and is a function of the initial flow shear. Additionally, it is
      demonstrated that there is a fundamental difference between the evolution of a
      problem at S = 200 and S = 10,000.

PMID- 12059481
TI  - Double Z-pinch hohlraum drive with excellent temperature balance for symmetric
      inertial confinement fusion capsule implosions.
AB  - A double Z pinch driving a cylindrical secondary hohlraum from each end has been
      developed which can indirectly drive intertial confinement fusion capsule
      implosions with time-averaged radiation fields uniform to 2%-4%. 2D time
      dependent view factor and 2D radiation hydrodynamic simulations using the
      measured primary hohlraum temperatures show that capsule convergence ratios of at
      least 10 with average distortions from sphericity of <Delta r>/r<or=30% are
      possible on the Z accelerator and may meet radiation symmetry requirements for
      scaling to fusion yields of >200 MJ.

PMID- 12059482
TI  - Reconnection and the ideal evolution of magnetic fields.
AB  - A magnetic evolution is ideal if it is consistent with the field being embedded
      in a perfectly conducting fluid. Faraday's law implies the evolution is ideal
      when the parallel component of the electric field is the derivative of a scalar
      potential, a condition that generically holds in any local region of space.
      Reconnection requires the non-existence of such a potential. In systems with two
      periodic directions, non-existence focuses reconnection onto the surfaces in
      which the magnetic field lines close on themselves, the rational surfaces. This
      rational surface effect does not arise in astrophysics but does appear in
      periodic simulation codes. Effects that could give astrophysical reconnection are
      discussed.

PMID- 12059483
TI  - Enhancement of proton acceleration by hot-electron recirculation in thin foils
      irradiated by ultraintense laser pulses.
AB  - MeV-proton production from solid targets irradiated by 100-fs laser pulses at
      intensities above 1x10(20) W cm(-2) has been studied as a function of initial
      target thickness. For foils 100 microm thick the proton beam was characterized by
      an energy spectrum of temperature 1.4 MeV with a cutoff at 6.5 MeV. When the
      target thickness was reduced to 3 microm the temperature was 3.2+/-0.3 MeV with a
      cutoff at 24 MeV. These observations are consistent with modeling showing an
      enhanced density of MeV electrons at the rear surface for the thinnest targets,
      which predicts an increased acceleration and higher proton energies.

PMID- 12059484
TI  - Abrasive wear on the atomic scale.
AB  - A scanning force microscope in ultrahigh vacuum has been used to realize and
      detect atomic-scale abrasion on KBr(001). The continuous time evolution of the
      lateral force under scratching reveals that the wear mechanism is due to the
      removal and the rearrangement of single ion pairs. The debris is reorganized in
      regular terraces with the same periodicity and orientation as the unscratched
      surface, as in local epitaxial growth. The applied load has a strong influence on
      the abrasive process, whereas the scan velocity is less relevant.

PMID- 12059485
TI  - Anomalous LO phonon lifetime in AlAs.
AB  - The temperature dependence of the frequencies and linewidths of the Raman-active
      longitudinal optical (LO) phonons in GaAs and AlAs have been measured. The low
      temperature lifetime of the LO phonon in AlAs is found to be 9.7 ps, very close
      to the corresponding GaAs value of 9.5 ps. This contradicts early theoretical
      predictions. The agreement between theory and experiment can be restored when the
      accidental degeneracy between the AlAs LO phonon frequency and a feature in the
      two-phonon density of states is taken into account.

PMID- 12059486
TI  - Universal intermediate phases of dilute electronic and molecular glasses.
AB  - Generic intermediate phases with anomalous properties exist over narrow
      composition ranges adjacent to connectivity transitions. Analysis of both simple
      classical and complex quantum percolation shows how topological concepts can be
      used to understand many mysterious properties of high temperature
      superconductors, including the remarkably similar phase diagrams of La(2
      x)Sr(x)CuO4 and C60(+y). Predictions are made for novel threshold behavior of the
      impurity band metal-insulator transition in two dimensions.

PMID- 12059487
TI  - Flexible Ab initio boundary conditions: simulating isolated dislocations in bcc
      Mo and Ta.
AB  - We report the first ab initio density-functional study of the strain field and
      Peierls stress of isolated <111> screw dislocations in bcc Mo and Ta. The local
      dislocation strain field is self-consistently coupled to the long-range elastic
      field using a flexible boundary condition method. This reduces the mesoscopic
      atomistic calculation to one involving only degrees of freedom near the
      dislocation core. The predicted equilibrium core for Mo is significantly
      different from previous atomistic results and the Peierls stress shows
      significant non-Schmid behavior as expected for the bcc metals.

PMID- 12059488
TI  - 5f electron localization-delocalization transition from UPd3 to UPt3.
AB  - The electronic structures of URh (3), UPd (3), UPt (3), and UAu (3) are
      calculated with the self-interaction corrected local-spin-density approximation.
      We find that only in URh (3) the f electrons are fully delocalized. UPt (3) has
      one f electron localized at each U site, while a localized f(2) configuration of
      the U ion is found for UPd (3). It is predicted that, upon application of a
      pressure of 25 GPa, UPd (3) will acquire the f(1) configuration and possibly
      exhibit heavy-fermion behavior. We find that UAu (3) is characterized by the same
      mixed localized-delocalized f-electron manifold as UPd (3).

PMID- 12059489
TI  - Thermoelectric power of bismuth nanocomposites.
AB  - Because of the increase in the electronic density of states in low-dimensional
      systems, semiconductor quantum wires constitute a most promising thermoelectric
      material. We report here the first experimental observation of a very large
      enhancement of the thermoelectric power of composites containing bismuth
      nanowires with diameters of 9 and 15 nm, embedded in porous alumina and porous
      silica. The temperature dependence of the electrical resistance shows that the
      samples are semiconductors with energy gaps between 0.17 and 0.4 eV, consistent
      with the theoretical predictions.

PMID- 12059490
TI  - Theory of quantum Hall nematics.
AB  - Transport measurements on two-dimensional electron systems in moderate magnetic
      fields suggest the existence of a spontaneously orientationally ordered,
      compressible liquid state. We develop and analyze a microscopic theory of such a
      "quantum Hall nematic" (QHN) phase, predict the existence of a novel, highly
      anisotropic q(3) density-director mode, find that the T = 0 long-range
      orientational order is unstable to weak disorder, and compute the tunneling into
      such a strongly correlated state. This microscopic approach is supported and
      complemented by a hydrodynamic model of the QHN, which, in the dissipationless
      limit, reproduces the modes of the microscopic model.

PMID- 12059491
TI  - Onset of energy dissipation in ballistic atomic wires.
AB  - Electronic transport at finite voltages in free-standing gold atomic chains of up
      to seven atoms in length is studied at low temperatures using a scanning
      tunneling microscope. The conductance vs voltage curves show that transport in
      these single-mode ballistic atomic wires is nondissipative up to a finite voltage
      threshold of the order of several mV. The onset of dissipation and resistance
      within the wire corresponds to the excitation of the atomic vibrations by the
      electrons traversing the wire and is very sensitive to strain.

PMID- 12059492
TI  - Possible pairing-induced even-denominator fractional quantum Hall effect in the
      lowest Landau level.
AB  - We report on our theoretical investigations that point to the possibility of a
      fractional quantum Hall effect with partial spin polarization at nu = 3/8. The
      physics of the incompressible state proposed here involves p-wave pairing of
      composite fermions in the spin reversed sector. The temperature and magnetic
      field regimes for the realization of this state are estimated.

PMID- 12059493
TI  - Differential sum rule for the relaxation rate in the cuprates.
AB  - Motivated by recent experiments by Basov et al., we study the differential sum
      rule for the effective scattering rate 1/tau(omega). We show that, in a dirty BCS
      superconductor, the area under 1/tau(omega) does not change between the normal
      and the superconducting states. For magnetically mediated pairing, a similar
      result holds between T<T(c) and T>or=T(c), while, in the pseudogap phase,
      1/tau(omega) is just suppressed compared to 1/tau(omega) in the normal state. We
      argue that this violation of the differential sum rule in the pseudogap phase is
      due to the absence of the feedback effects from the pairing.

PMID- 12059494
TI  - de Haas-van Alphen effect in single crystal MgB2.
AB  - We report observations of quantum oscillations in single crystals of the high
      temperature superconductor MgB2. Three de Haas-van Alphen frequencies are clearly
      resolved. Comparison with band structure calculations strongly suggests that two
      of these come from a single warped Fermi surface tube along the c direction, and
      that the third arises from cylindrical sections of an in-plane honeycomb network.
      The measured values of the effective mass range from (0.44-0.68)m(e). By
      comparing these to calculated band masses, we find that the electron-phonon
      coupling strength lambda is a factor of approximately 3 larger for the c-axis
      tube orbits than for the in-plane network orbit, in accord with recent
      microscopic calculations.

PMID- 12059496
TI  - Phase diagram of the anisotropic Kondo chain.
AB  - We establish the phase diagram of the one-dimensional anisotropic Kondo lattice
      model at T = 0 using a generalized two-dimensional classical Coulomb gas
      description. We analyze the problem by means of a renormalization group
      treatment. We find that the phase diagram contains regions of paramagnetism,
      partial and full ferromagnetic order.

PMID- 12059495
TI  - Direct evidence for an intrinsic square vortex lattice in the overdoped high-
      T(c) superconductor La(1.83)Sr(0.17)CuO(4+delta).
AB  - We report here the first direct observations of a well ordered vortex lattice in
      the bulk of a La(2-x)Sr(x)CuO(4+delta) single crystal (slightly overdoped, x =
      0.17). Our small angle neutron scattering investigation of the mixed phase
      reveals a crossover from triangular to square coordination with increasing
      magnetic field. The existence of an intrinsic square vortex lattice has never
      been observed in high-temperature superconductors and is indicative of the
      coupling of the vortex lattice to a source of anisotropy, such as those provided
      by a d-wave order parameter or the presence of stripes.

PMID- 12059498
TI  - Interaction-induced collapse of a section of the Fermi sea in the zigzag Hubbard
      ladder.
AB  - Using the next-nearest-neighbor (zigzag) Hubbard chain as a one-dimensional
      model, we investigate the influence of interactions on the position of the Fermi
      wave vectors with the density-matrix renormalization-group technique. For
      suitable choices of the hopping parameters we observe that electron-electron
      correlations induce very different renormalizations for the two different Fermi
      wave vectors, which ultimately lead to a complete destruction of one section of
      the Fermi sea in a quantum critical point.

PMID- 12059497
TI  - Magnetism of the Fe/ZnSe(001) interface.
AB  - The magnetism of epitaxial ultrathin films of Fe on ZnSe(001) has been
      investigated by x-ray magnetic circular dichroism down to the submonolayer
      regime. In contrast to other metallic ferromagnet/semiconductor interfaces, no
      reduction of the Fe magnetic moment was found at the Fe/ZnSe(001) interface.
      Furthermore, a significant enhancement of the Fe magnetic moment compared to the
      bulk value was observed for coverages up to one monolayer in agreement with
      theoretical predictions. We also demonstrate that the magnetic properties of the
      Fe/ZnSe(001) interface remain stable against thermal annealing up to 300 degrees
      C, a prerequisite for the future development of efficient spintronics devices.

PMID- 12059499
TI  - Metamagnetic quantum criticality in metals.
AB  - We present a renormalization group treatment of metamagnetic quantum criticality
      in metals. We show that for clean systems the universality class is that of the
      overdamped, conserving (dynamical exponent z = 3) Ising type. We obtain detailed
      results for the field and temperature dependence of physical quantities including
      the differential susceptibility, resistivity, and specific heat. Our results are
      shown to be in quantitative agreement with data on Sr3Ru2O7 except very near to
      the critical point itself.

PMID- 12059500
TI  - Magnetic relaxation of interacting co clusters: crossover from two- to three
      dimensional lattices.
AB  - The influence that dipole-dipole interactions exert on the dynamics of the
      magnetization of nanometer-sized Co clusters has been studied by means of ac and
      dc susceptibility experiments. These clusters grow in a quasiordered layered
      structure, where all relevant parameters can be tailored and measured
      independently. Our data show without ambiguity that the magnetic relaxation
      becomes slower as the degree of interaction increases. The effective activation
      energy increases linearly with the number of nearest neighbor clusters, evolving
      from the value for a 2D layer to the fully 3D behavior, which is nearly reached
      for five layers. The experimental results agree quantitatively with the
      predictions of a simple model.

PMID- 12059501
TI  - Colossal paramagnetic moments in metallic carbon nanotori.
AB  - Carbon nanostructures with unusually large paramagnetic moments have been
      discovered in a theoretical study of the electronic and magnetic properties of
      carbon nanotubes bent into toroids. Specifically, nanotori formed from metallic
      nanotubes with lambda(F) = 3T, where lambda(F) is the Fermi wavelength and T the
      translation vector of the nanotube, exhibit giant paramagnetic moments at
      selected radii ("magic radii"), while the ones with lambda(F) = T are
      paramagnetic at any radius. The large paramagnetic moment is due to the interplay
      between the toroidal geometry and the ballistic motion of the pi electrons in the
      metallic nanotube.

PMID- 12059502
TI  - 2p Photoionization of atomic Ni: a comparison with Ni metal and NiO
      photoionization.
AB  - The photoabsorption spectrum of the 2p-3d resonances and the 2p photoelectron
      spectrum of atomic Ni were investigated both experimentally and theoretically.
      The analysis of the spectra takes into account that at the evaporation
      temperature of the metal at about 1800 K the fine structure states 3d(8) 4s(2) 3F
      and 3d(9) 4s 3D of both configurations 3d(8) 4s(2) and 3d(9) 4s are populated.
      The population of these two configurations offers the unique possibility for a
      comparison with the corresponding spectra in the condensed phase (Ni metal and
      NiO) where current configuration interaction calculations use the mixture of the
      configurations (3d,4s)(10). By using our theoretical description of the 2p
      photoionization new insight into these condensed phase spectra is found.

PMID- 12059503
TI  - Direct estimations of linear and nonlinear functionals of a quantum state.
AB  - We present a simple quantum network, based on the controlled-SWAP gate, that can
      extract certain properties of quantum states without recourse to quantum
      tomography. It can be used as a basic building block for direct quantum
      estimations of both linear and nonlinear functionals of any density operator. The
      network has many potential applications ranging from purity tests and eigenvalue
      estimations to direct characterization of some properties of quantum channels.
      Experimental realizations of the proposed network are within the reach of quantum
      technology that is currently being developed.

PMID- 12059504
TI  - Noise-induced entrainment and stochastic resonance in human brain waves.
AB  - We present the first observation of stochastic resonance (SR) in the human
      brain's visual processing area. The novel experimental protocol is to stimulate
      the right eye with a subthreshold periodic optical signal and the left eye with a
      noisy one. The stimuli bypass sensory organs and are mixed in the visual cortex.
      With many noise sources present in the brain, higher brain functions, e.g.,
      perception and cognition, may exploit SR.

PMID- 12059505
TI  - Coexistence of liquid and solid phases in flowing soft-glassy materials.
AB  - Magnetic-resonance-imaging rheometrical experiments show that concentrated
      suspensions or emulsions cannot flow steadily at a uniform rate smaller than a
      critical value (gamma(c)). As a result, a "liquid" region (sheared rapidly, i.e.,
      at a rate larger than gamma(c)) and a "solid" region (static) coexist. The
      behavior of the fluid in the liquid region follows a simple power-law model,
      while the extent of the solid region increases with the degree of jamming of the
      material.

PMID- 12059506
TI  - Comment on "Stable quantum computation of unstable classical chaos".

PMID- 12059508
TI  - Comment on "Factorial moments analyses show a characteristic length scale in DNA
      sequences".

PMID- 12059510
TI  - Trapping reaction with mobile traps.
AB  - We present the Monte Carlo results for the two-species trapping reaction A+B-->B
      with diffusing A and B on lattices in one, two, and three dimensions. We use an
      algorithm that permits one to simulate the survival probabilities of A particles
      down to <10(-30) with high accuracy. The results for the survival probability
      agree much better with the exact asymptotic predictions of Bramson and Lebowitz
      [Phys. Rev. Lett. 61, 2397 (1988)] than with the heuristics of Kang and Redner
      [J. Phys. A 17, L451 (1984)]. But there are very large deviations from either,
      which show that even these simulations are far from asymptotia. This is supported
      by the rms displacement of A particles, which clearly shows that the asymptotic
      regime has not been reached, at least for d=2 and d=3.

PMID- 12059511
TI  - Definition of temperature in dense granular media.
AB  - In this paper we report the measurement of a pseudotemperature for compacting
      granular media on the basis of the fluctuation-dissipation relations in the aging
      dynamics of a model system. From the violation of the fluctuation-dissipation
      theorem emerges an effective temperature (a dynamical temperature T(dyn)) whose
      value depends on the particle density. We compare the results for T(dyn) at
      several densities with the values of Edwards' compactivity at the corresponding
      densities [S. F. Edwards, in Granular Matter: An Interdisciplinary Approach,
      edited by A. Mehta (Springer-Verlag, New York, 1994) and references therein]. It
      turns out that the dynamical temperature and Edwards' compactivity coincide on a
      large range of densities, opening in this way the door to experimental checks as
      well as theoretical constructions.

PMID- 12059512
TI  - Foam analogy in charged colloidal crystals.
AB  - We model charged colloidal suspensions using an analogy with foams. We study the
      solid-solid phase transitions of these systems as a function of particle volume
      fraction and ionic strength. The screened-Coulomb interaction is replaced by an
      interaction between walls of the Voronoi cells around each particle. We fit the
      surface charge to reproduce the phase diagram for the charged suspension studied
      by Sirota et al. [Phys. Rev. Lett. 62, 1524 (1989)]. With this fit parameter we
      are able to calculate the elastic moduli of the system and find good agreement
      with the available data.

PMID- 12059513
TI  - Anomalous dynamic scaling in locally conserved coarsening of fractal clusters.
AB  - We report two-dimensional phase-field simulations of locally conserved coarsening
      dynamics of random fractal clusters with fractal dimension D=1.7 and 1.5. The
      correlation function, cluster perimeter, and solute mass are measured as
      functions of time. Analyzing the correlation function dynamics, we identify two
      different time-dependent length scales that exhibit power laws in time. The
      exponents of these power laws do not show any dependence on D; one of them is
      apparently the "classical" exponent 1/3. The solute mass versus time exhibits
      dynamic scaling with a D-dependent exponent, in agreement with a simple scaling
      theory.

PMID- 12059514
TI  - Liquid-solid transition in a model hard sphere system of block copolymer
      micelles.
AB  - The transition between micellar liquid and face-centered-cubic crystalline solid
      in a solution of an amphiphilic diblock copolymer is investigated by small-angle
      x-ray scattering and rheology. The system is well described by the hard sphere
      model and there is no evidence for percolation driven by attractive interactions,
      in contrast to previous reports. Instead, a coexistence region separates liquid
      and crystal phases.

PMID- 12059515
TI  - Faceted monodomains of liquid crystal smectic blue phases.
AB  - Smectic blue phases (BP(Sm)) are mesophases of thermotropic liquid crystals,
      which exhibit both three-dimensional orientational order, such as classical blue
      phases, and smectic positional order. The BP(Sm) phases appear as the three
      dimensional counterpart of the twist grain boundary phases. By growing large
      faceted monocrystals of BP(Sm) phase, we provide, for the first time at the
      length scale of the lattice parameter, information on the symmetry of the
      orientational unit cell. This study leads us to suggest an orthorhombic
      structure, contrary to the previous results obtained by x-ray scattering at the
      length scale of the smectic order.

PMID- 12059516
TI  - Molecular self-diffusion in a columnar liquid crystalline phase determined by
      deuterium NMR.
AB  - We report translational diffusion coefficients in a columnar phase of a discotic
      liquid crystal formed by a triphenylene-based compound. The experiments were
      performed using 2H stimulated-echo-type pulsed-field-gradient spin-echo NMR
      applied to a chain-deuterated sample. The diffusion coefficients were found in
      the range of 1x10(-14)-4x10(-14) m2/s, three orders of magnitude lower than in
      the isotopic phase of the same compound. This, together with the high activation
      energy obtained in columnar phase, indicates that the diffusion is dominated by
      solidlike jump processes.

PMID- 12059518
TI  - Molecular dynamics simulation of polymer crystallization from an oriented
      amorphous state.
AB  - The molecular process of crystallization from an oriented amorphous state was
      reproduced by molecular dynamics simulation for a realistic polyethylene model.
      The initial oriented amorphous state was obtained by uniaxially drawing an
      isotropic glassy state at 100 K. By the temperature jump from 100 K to 330 K,
      there occurred crystallization into the fiber structure, during the process of
      which we observed the developments of various order parameters. The real-space
      image and its Fourier transform revealed that a hexagonally ordered domain was
      initially formed, and then a highly ordered crystalline state with stacked
      lamellas developed after further adjustment of the relative heights of the chains
      along their axes.

PMID- 12059517
TI  - Hydrogen-bonded silica gels dispersed in a smectic liquid crystal: a random field
      XY system.
AB  - The effect on the nematic to smectic-A transition in octylcyanobiphenyl (8CB) due
      to dispersions of hydrogen-bonded silica (aerosil) particles is characterized
      with high-resolution x-ray scattering. The particles form weak gels in 8CB
      creating a quenched disorder that replaces the transition with the growth of
      short-range smectic correlations. The correlations include thermal critical
      fluctuations that dominate at high temperatures and a second contribution that
      quantitatively matches the static fluctuations of a random field system and
      becomes important at low temperatures.

PMID- 12059519
TI  - Evidence for an unusual dynamical-arrest scenario in short-ranged colloidal
      systems.
AB  - Extensive molecular dynamics simulation studies of particles interacting via a
      short-ranged attractive square-well potential are reported. The calculated loci
      of constant diffusion coefficient D in the temperature-packing fraction plane
      show a reentrant behavior, i.e., an increase of diffusivity on cooling,
      confirming an important part of the high volume-fraction dynamical-arrest
      scenario earlier predicted by theory for particles with short-ranged potentials.
      The more efficient localization mechanism induced by the short-range bonding
      provides, on average, additional free volume as compared to the hard-sphere case
      and results in faster dynamics.

PMID- 12059520
TI  - Phase synchronization and stochastic resonance effects in the crayfish caudal
      photoreceptor.
AB  - We study the nonlinear response of the crayfish caudal photoreceptor to periodic
      mechanical stimuli in terms of stochastic synchronization. The amplitude and
      frequency of the mechanical stimuli and the light level are used as control
      parameters. The system shows multiple locking regions as the stimulus frequency
      is varied. We find that the synchronization index increases as the signal-to
      noise ratio (SNR) of the periodic drive, in response to increasing light levels;
      this effect exhibits features similar to stochastic resonance. We demonstrate a
      nonlinear rectification effect in which the SNR of the second harmonic of the
      input stimulus increases as the light level is raised, and show that the
      corresponding synchronization index increases as the SNR of the second harmonic.

PMID- 12059521
TI  - Subharmonic stochastic synchronization and resonance in neuronal systems.
AB  - We study the response of a model neuron, driven simultaneously by noise and at
      least two weak periodic signals. We focus on signals with frequencies components
      kf(0),(k+1)f(0),...(k+n)f(0) with k>1. The neuron's output is a sequence of
      pulses spaced at random interpulse intervals. We find an optimum input noise
      intensity for which the output pulses are spaced approximately 1/f(0), i.e.,
      there is a stochastic resonance (SR) at a frequency missing in the input. Even
      higher noise intensities uncover additional, but weaker, resonances at
      frequencies present in the input. This is a different form of SR whereby the most
      robust resonance is the one enhancing a frequency, which is absent in the input,
      and which is not possible to recover via any linear processing. This can be
      important in understanding sensory systems including the neuronal mechanism for
      perception of complex tones.

PMID- 12059522
TI  - Learning and predicting time series by neural networks.
AB  - Artificial neural networks which are trained on a time series are supposed to
      achieve two abilities: first, to predict the series many time steps ahead and
      second, to learn the rule which has produced the series. It is shown that
      prediction and learning are not necessarily related to each other. Chaotic
      sequences can be learned but not predicted while quasiperiodic sequences can be
      well predicted but not learned.

PMID- 12059523
TI  - Temporal and spatial properties of fluctuations below a supercritical primary
      bifurcation to traveling oblique-roll electroconvection.
AB  - We present measurements of thermally-induced oblique-roll traveling-wave (TW)
      fluctuations below the supercritical primary bifurcation to electroconvection
      (EC) in the nematic liquid crystal 4-ethyl-2-fluoro-4'-[2-(trans-4
      pentylcyclohexyl)ethyl]-biphenyl (I52). First we analyze time sequences of one
      dimensional shadowgraph images taken parallel to the director to obtain the TW
      frequency omega and the fluctuation lifetime tau. Within our resolution we find
      that omega is independent of epsilon [triple bond] V/V(c)-1 (V is the applied
      voltage amplitude and V(c) its value at the onset of convection). Contrary to
      linear theory, the relaxation rate 1/tau remains finite at the bifurcation. Next
      we present the analysis of temporally uncorrelated two-dimensional shadowgraph
      images of the fluctuations for several values of the electrical conductivity
      sigma. We fitted an anisotropic two-dimensional Lorentzian function,
      corresponding to oblique-roll EC, to the time-averaged structure factors S(k)
      derived from the images. This yielded information about the components of the
      mean wave vector k(0) and about the correlation length xi as a function of sigma
      and epsilon. The angle of obliqueness theta of the roll patterns was independent
      of sigma but decreased anomalously as epsilon approached zero. The modulus k(0)
      of k(0) depended on sigma. It also showed an anomalous reduction close to onset.
      The anomalous epsilon dependence of k(0) and theta disagrees with linear theory,
      which predicts a smooth, essentially linear dependence on epsilon, and presumably
      is caused by nonlinear interactions between the fluctuations.

PMID- 12059524
TI  - Stochastic modeling of daily temperature fluctuations.
AB  - Classical spectral, Hurst, and detrended fluctuation analysis have been revealed
      asymptotic power-law correlations for daily average temperature data. For short
      time intervals, however, strong correlations characterize the dynamics that
      permits a satisfactory description of temperature changes as a low order linear
      autoregressive process (dominating the texts on climate research). Here we
      propose a unifying stochastic model reproducing correlations for all time scales.
      The concept is an extension of a first-order autoregressive model with power-law
      correlated noise. The inclusion of a nonlinear "atmospheric response function"
      conveys the observed skew for the amplitude distribution of temperature
      fluctuations. While stochastic models cannot help to understand the physics
      behind atmospheric processes, they are capable to extract useful features
      promoting to benchmark physical models, an example is shown. Possible
      applications for other systems of strong short-range and asymptotic power-law
      correlations are discussed.

PMID- 12059525
TI  - String ratchets: ac driven asymmetric kinks.
AB  - We simulated numerically the time evolution of a one-kink bearing, damped elastic
      string sitting on noiseless periodic substrates of two types: (I) asymmetric,
      time independent, (II) symmetric, periodically deformable. An asymmetric kink
      subjected to an ac drive is shown to drift steadily with finite average speed
      independent of its initial kinetic conditions. In the overdamped regime the
      resulting net kink transport can be attributed to the rectification of the
      Brownian motion of a pointlike particle with oscillating mass. For intermediate
      to low damping completely different features show up, due to the finite size of
      the objects being transported; in particular, the kink current hits a maximum for
      an optimal value of the damping constant, resonates at the kink internal-mode
      frequency and, finally, reverses sign within a certain range of the drive
      parameters.

PMID- 12059526
TI  - Pole topology of the structure functions of continuous systems.
AB  - We develop a theory of the pole topology of the Laplace transform of the
      structure functions of continuous N component systems based on the Wiener-Hopf
      technique. We classify systems according to the spectrum of the NxN matrix Q(t),
      with elements Q(ij)(t)=delta(ij)-2pi square root [rho(i)rho(j)]integrale(
      tr)q(ij)(r)dr, associated with their factor functions q(ij)(r). For the simplest
      nontrivial class of systems--namely, that with only two eigenvalues of Q(t)
      different from one--a full and explicit analysis of the pole topology is
      possible. We illustrate the theory with exactly solvable examples, such as the
      Percus-Yevick equation for arbitrary mixtures of hard spheres (HS) and
      polydisperse HS and the mean spherical model for binary mixtures of adhesive
      spheres.

PMID- 12059527
TI  - Inertial effects in the anomalous dielectric relaxation of rotators in space.
AB  - The linear dielectric response of an assembly of noninteracting linear
      (needlelike) dipole molecules (each of which is free to rotate in space) is
      evaluated in the context of fractional dynamics. The infinite hierarchy of
      differential-recurrence relations for the relaxation functions appropriate to the
      dielectric response is derived by using the underlying inertial fractional Fokker
      Planck (fractional Klein-Kramers) equation. On solving this hierarchy in terms of
      continued fractions (as in the normal rotational diffusion), the complex dynamic
      susceptibility is obtained and is calculated for typical values of the model
      parameters. It is shown that the model can reproduce nonexponential anomalous
      dielectric relaxation behavior at low frequencies (omega tau< or =1, where tau is
      the Debye relaxation time) and the inclusion of inertial effects ensures that
      optical transparency is regained at very high frequencies (in the far infrared
      region) so that Gordon's sum rule for integral dipolar absorption is satisfied.

PMID- 12059528
TI  - Generalized quantum Fokker-Planck, diffusion, and Smoluchowski equations with
      true probability distribution functions.
AB  - Traditionally, quantum Brownian motion is described by Fokker-Planck or diffusion
      equations in terms of quasiprobability distribution functions, e.g., Wigner
      functions. These often become singular or negative in the full quantum regime. In
      this paper a simple approach to non-Markovian theory of quantum Brownian motion
      using true probability distribution functions is presented. Based on an initial
      coherent state representation of the bath oscillators and an equilibrium
      canonical distribution of the quantum mechanical mean values of their coordinates
      and momenta, we derive a generalized quantum Langevin equation in c numbers and
      show that the latter is amenable to a theoretical analysis in terms of the
      classical theory of non-Markovian dynamics. The corresponding Fokker-Planck,
      diffusion, and Smoluchowski equations are the exact quantum analogs of their
      classical counterparts. The present work is independent of path integral
      techniques. The theory as developed here is a natural extension of its classical
      version and is valid for arbitrary temperature and friction (the Smoluchowski
      equation being considered in the overdamped limit).

PMID- 12059529
TI  - Kinetic behavior of aggregation processes with complete annihilation.
AB  - The kinetic behavior of an aggregation-annihilation process of an n-species (n>
      or =2) system is studied. In this model, an irreversible aggregation reaction
      occurs between any two clusters of the same species and an irreversible complete
      annihilation reaction occurs between any two different species. Based on the mean
      field theory, we investigate the rate equations of the process with constant
      reaction rates to obtain the asymptotic solutions for the cluster-mass
      distributions. We find that the cluster-mass distribution of each species
      satisfies a modified scaling law, which reduces to the standard scaling law in
      some special cases. The scaling exponents of the system may strongly depend on
      the reaction rates for most cases; however, for the case with all the aggregation
      rates twice the annihilation rate, these exponents depend only on the initial
      concentrations. All the species annihilate each other completely except in the
      case in which at least one aggregation rate is less than twice the annihilation
      rate.

PMID- 12059530
TI  - Trichotomous-noise-induced catastrophic shifts in symbiotic ecosystems.
AB  - An N-species Lotka-Volterra stochastic model of a symbiotic ecological system
      with the Verhulst self-regulation mechanism is considered. The effect of
      fluctuating environment on the carrying capacity of a population is modeled as
      the colored three-level Markovian (trichotomous) noise. In the framework of the
      mean-field theory an explicit self-consistency equation for stationary states is
      presented. Stability and instability conditions and colored-noise-induced
      discontinuous transitions (catastrophic shifts) in the model are investigated. In
      some cases the mean field exhibits hysteresis as a function of the noise
      parameters. It is shown that the occurrence of catastrophic shifts can be
      controlled by noise parameters, such as correlation time, amplitude, and
      flatness. The dependence of the critical coupling strengths on the noise
      parameters is found and illustrated by phase diagrams. Implications of the
      results on some modifications of the model are discussed.

PMID- 12059531
TI  - Moment evolution and level-crossing statistics in dichotomous and multilevel
      flows with time-dependent control parameters.
AB  - We study the dynamics of the first two moments and of threshold crossings by the
      stochastic trajectory in dichotomous diffusion x=xi(t), where xi(t) is a
      dichotomous Markov process. The transition rate of the latter is regarded as a
      control parameter and allowed to have specified time variations. The stabilizing
      or destabilizing effect of this variation is demonstrated, and qualitative
      changes in the statistical properties of the system are shown to occur. The
      analysis is then extended to linear dichotomous flow, and to a generalization of
      dichotomous diffusion in which x is driven by a multilevel Markov noise.

PMID- 12059533
TI  - Diffusivity dependence of ozone depletion over the midnorthern latitudes.
AB  - The mixing and reaction properties of advected chemicals (and passive scalars)
      are determined by the fractal dimension D of the interface between the chemicals.
      We show that the scaling of the amount m of reacted chemicals with diffusivity
      kappa is m(0)-m(kappa) proportional, proportional to kappa(1-D/2) in the two
      dimensional case. This relation is valid in a range of times and diffusivities
      where the diffusive length scales of the chemicals are within the range of scales
      where the chemical interface has a well-defined fractal dimension. We apply the
      relation to the problems of chlorine deactivation and ozone depletion over the
      midnorthern latitudes. We determine numerically the fractal dimension of an
      interface advected by stratospheric winds. This allows us, first, to explain the
      diffusivity dependence of chlorine deactivation and ozone depletion that was
      previously observed in numerical simulations (Tan et al., J. Geophys. Res.,
      [Atmos.] 103, 1585 (1998)) and, second, to extrapolate the results of such
      simulations down to realistically low diffusivities.

PMID- 12059532
TI  - Oscillatory systems driven by noise: frequency and phase synchronization.
AB  - The phenomenon of effective phase synchronization in stochastic oscillatory
      systems can be quantified by an average frequency and a phase diffusion
      coefficient. A different approach to compute the noise-averaged frequency is put
      forward. The method is based on a threshold crossing rate pioneered by Rice.
      After the introduction of the Rice frequency for noisy systems we compare this
      quantifier with those obtained in the context of other phase concepts, such as
      the natural and the Hilbert phase, respectively. It is demonstrated that the
      average Rice frequency <omega>R typically supersedes the Hilbert frequency
      <omega>H, i.e. <omega>R > or = <omega>H. We investigate next the Rice frequency
      for the harmonic and the damped, bistable Kramers oscillator, both without and
      with external periodic driving. Exact and approximative analytic results are
      corroborated by numerical simulation results. Our results complement and extend
      previous findings for the case of noise-driven inertial systems.

PMID- 12059534
TI  - Large-deviation functions for nonlinear functionals of a Gaussian stationary
      Markov process.
AB  - We introduce a general method, based on a mapping onto quantum mechanics, for
      investigating the large-T limit of the distribution P(r,T) of the nonlinear
      functional r[V]=(1/T)integral(T)(0)dT' V[X(T')], where V(X) is an arbitrary
      function of the stationary Gaussian Markov process X(T). For T-->infinity at
      fixed r we obtain P(r,T) approximately exp[-theta(r)T], where theta(r) is a large
      deviation function. We present explicit results for a number of special cases
      including V(X)=XH(X) [where H(X) is the Heaviside function], which is related to
      the cooling and the heating degree days relevant to weather derivatives.

PMID- 12059535
TI  - Uninfected random walkers in one dimension.
AB  - We consider a system of unbiased diffusing walkers (A(Phi)<-->(Phi)A) in one
      dimension with random initial conditions. We investigate numerically the relation
      between the fraction of walkers U(t) which have never encountered another walker
      up to time t, calling such walkers "uninfected" and the fraction of sites P(t)
      which have never been visited by a diffusing particle. We extend our study to
      include the A+B--> Phi diffusion-limited reaction in one dimension, with equal
      initial densities of A and B particles distributed homogeneously at t=0. We find
      U(t) approximately [P(t)]gamma, with gamma approximately 1.39, in both models,
      though there is evidence that a smaller value of gamma is required for t-
      >infinity.

PMID- 12059536
TI  - Fraction of uninfected walkers in the one-dimensional Potts model.
AB  - The dynamics of the one-dimensional q-state Potts model, in the zero-temperature
      limit, can be formulated through the motion of random walkers which either
      annihilate (A+A-->Phi) or coalesce (A+A-->A) with a q-dependent probability. We
      consider all of the walkers in this model to be mutually infectious. Whenever two
      walkers meet, they experience mutual contamination. Walkers which avoid an
      encounter with another random walker up to time t remain uninfected. The fraction
      of uninfected walkers is known to obey a power-law decay U(t) approximately t(
      phi(q)), with a nontrivial exponent phi(q) [C. Monthus, Phys. Rev. E 54, 4844
      (1996); S. N. Majumdar and S. J. Cornell, ibid. 57, 3757 (1998)]. We probe the
      numerical values of phi(q) to a higher degree of accuracy than previous
      simulations and relate the exponent phi(q) to the persistence exponent theta(q)
      [B. Derrida, V. Hakim, and V. Pasquier, Phys. Rev. Lett. 75, 751 (1995)], through
      the relation phi(q)=gamma(q)theta(q) where gamma is an exponent introduced in [S.
      J. O'Donoghue and A. J. Bray, preceding paper, Phys. Rev. E 65, 051113 (2002)].
      Our study is extended to include the coupled diffusion-limited reaction A+A-->B,
      B+B-->A in one dimension with equal initial densities of A and B particles. We
      find that the density of walkers decays in this model as rho(t) approximately t(
      1/2). The fraction of sites unvisited by either an A or a B particle is found to
      obey a power law, P(t) approximately t(-theta) with theta approximately 1.33. We
      discuss these exponents within the context of the q-state Potts model and present
      numerical evidence that the fraction of walkers which remain uninfected decays as
      U(t) approximately t(-phi), where phi approximately 1.13 when infection occurs
      between like particles only, and phi approximately 1.93 when we also include
      cross-species contamination. We find that the relation between phi and theta in
      this model can also be characterized by an exponent gamma, where similarly,
      phi=gamma(theta).

PMID- 12059537
TI  - Nonequilibrium coupled Brownian phase oscillators.
AB  - A model of globally coupled phase oscillators under equilibrium (driven by
      Gaussian white noise) and nonequilibrium (driven by symmetric dichotomic
      fluctuations) is studied. For the equilibrium system, the mean-field state
      equation takes a simple form and the stability of its solution is examined in the
      full space of order parameters. For the nonequilbrium system, various asymptotic
      regimes are obtained in a closed analytical form. In a general case, the
      corresponding master equations are solved numerically. Moreover, the Monte Carlo
      simulations of the coupled set of Langevin equations of motion is performed. The
      phase diagram of the nonequilibrium system is presented. For the long time limit,
      we have found five regimes. Three of them can be obtained from the mean-field
      theory. One of them, the oscillating regime, cannot be predicted by the mean
      field method and has been detected in the Monte Carlo numerical experiments.

PMID- 12059538
TI  - Noise-induced dephasing of an ac-driven Josephson junction.
AB  - We consider the phase-locked dynamics of a Josephson junction driven by finite
      spectral-linewidth ac current. By means of a transformation, the effect of
      frequency fluctuations is reduced to an effective additive noise, the
      corresponding (large) dephasing time being determined, in the logarithmic
      approximation, by the Kramers expression for the lifetime. For sufficiently small
      values of the drive's amplitude, direct numerical simulations show agreement of
      the dependence of the dephasing activation energy on the ac drive's spectral
      linewidth and amplitude with analytical predictions. Solving the corresponding
      Fokker-Planck equation analytically, we find a universal dependence of the
      critical value of the effective phase-diffusion parameter on the drive's
      amplitude at the point of sharp transition from the phase-locked state to an
      unlocked one. However, for large values of the drive amplitude, saturation and
      subsequent decrease of the activation energy are revealed by simulations, which
      cannot be accounted for by the perturbative analysis. The same effect is found
      for a previously studied case of ac-driven Josephson junctions with intrinsic
      thermal noise. The predicted effects are relevant to applications to voltage
      standards, as they determine the stability of the Josephson phase-locked state.

PMID- 12059539
TI  - Structural relaxation in a system of dumbbell molecules.
AB  - The interaction-site-density-fluctuation correlators, the dipole-relaxation
      functions, and the mean-squared displacements of a system of symmetric dumbbells
      of fused hard spheres are calculated for two representative elongations of the
      molecules within the mode-coupling theory for the evolution of glassy dynamics.
      For large elongations, universal relaxation laws for states near the glass
      transition are valid for parameters and time intervals similar to the ones found
      for the hard-sphere system. Rotation-translation coupling leads to an enlarged
      crossover interval for the mean-squared displacement of the constituent atoms
      between the end of the von Schweidler regime and the beginning of the diffusion
      process. For small elongations, the superposition principle for the
      reorientational alpha process is violated for parameters and time intervals of
      interest for data analysis, and there is a strong breaking of the coupling of the
      alpha-relaxation scale for the diffusion process with that for representative
      density fluctuations and for dipole reorientations.

PMID- 12059540
TI  - Equilibration times in numerical simulation of structural glasses: comparing
      parallel tempering and conventional molecular dynamics.
AB  - Generation of equilibrium configurations is the major obstacle for numerical
      investigation of the slow dynamics in supercooled liquid states. The parallel
      tempering (PT) technique, originally proposed for the numerical equilibration of
      discrete spin-glass model configurations, has recently been applied in the study
      of supercooled structural glasses. We present an investigation of the ability of
      parallel tempering to properly sample the liquid configuration space at different
      temperatures, by mapping the PT dynamics into the dynamics of the closest local
      potential energy minima (inherent structures). Comparing the PT equilibration
      process with the standard molecular dynamics equilibration process we find that
      the PT does not increase the speed of equilibration of the (slow) configurational
      degrees of freedom.

PMID- 12059541
TI  - Molecular dynamics study of diffusion in a bilayer electron gas.
AB  - Molecular dynamics simulations of strongly coupled, classical electronic
      bilayers, interacting through the Coulomb potential, have been produced and
      studied. Values of the plasma coupling parameter Gamma between 10 and 80 and
      interlayer separations d from 0.1 to 3.0, (in units of Wigner-Seitz radius), were
      considered. The simulation results were used to calculate the intralayer and
      interlayer pair correlation functions and self-diffusion of charged particles in
      this system. The variation of self-diffusion with Gamma and d has been analyzed,
      and it is found that for the largest value of Gamma, the diffusion coefficient
      does not increase monotonically with layer separation, but has a distinct minimum
      for values of d slightly less than 1.

PMID- 12059543
TI  - Collision group and renormalization of the Boltzmann collision integral.
AB  - On the basis of a recently discovered collision group [V. L. Saveliev, in
      Rarefied Gas Dynamics: 22nd International Symposium, edited by T. J. Bartel and
      M. Gallis, AIP Conf. Proc. No. 585 (AIP, Melville, NY, 2001), p. 101], the
      Boltzmann collision integral is exactly rewritten in two parts. The first part
      describes the scattering of particles with small angles. In this part the
      infinity due to the infinite cross sections is extracted from the Boltzmann
      collision integral. Moreover, the Boltzmann collision integral is represented as
      a divergence of the flow in velocity space. Owing to this, the role of collisions
      in the kinetic equation can be interpreted in terms of the nonlocal friction
      force that depends on the distribution function.

PMID- 12059542
TI  - Properties of stationary nonequilibrium states in the thermostatted periodic
      Lorentz gas: the multiparticle system.
AB  - We study the stationary nonequilibrium states of N-point particles moving under
      the influence of an electric field E among fixed obstacles (disk) in a two
      dimensional torus. The total kinetic energy of the system is kept constant
      through a Gaussian thermostat that produces a velocity dependent mean field
      interaction between the particles. The current and the particle distribution
      functions are obtained numerically and compared for small /E/ with analytic
      solutions of a Boltzmann-type equation obtained by treating the collisions with
      the obstacles as random independent scatterings. The agreement is surprisingly
      good for both small and large N. The latter system in turn agrees with a self
      consistent one-particle evolution expected to hold in the N-->infinity limit.

PMID- 12059544
TI  - Reference-point-independent dynamics of molecular liquids and glasses in the
      tensorial formalism.
AB  - We apply the tensorial formalism to the dynamics of molecular liquids and
      glasses. This formalism separates the degrees of freedom into translational and
      orientational ones. Using the Mori-Zwanzig projection formalism, the equations of
      motion for the tensorial density correlators S(lmn,l'm'n')(q-->,t) are derived.
      For this we show how to choose the slow variables such that the resulting Mori
      Zwanzig equations are covariant under a change of the reference point of the body
      fixed frame. We also prove that the memory kernels obtained from mode-coupling
      theory (MCT) including all approximations preserve the covariance. This
      covariance makes, e.g., the glass transition point, the two universal scaling
      laws and particularly the corresponding exponents independent on the reference
      point and on the mass and moments of inertia, i.e., they only depend on the
      properties of the potential energy landscape. Finally, we show that the
      corresponding MCT questions for linear molecules can be obtained from those for
      arbitrary molecules and that they differ from earlier equations that are not
      covariant.

PMID- 12059545
TI  - Cooling of a lattice granular fluid as an ordering process.
AB  - We present a microscopic model of granular medium to study the role of dynamical
      correlations and the onset of spatial order induced by the inelasticity of the
      interactions on the velocity field. In spite of its simplicity and intrinsic
      limitations, it features several aspects of the rich phenomenology observed in
      granular materials and allows to make contact with other topics of statistical
      mechanics such as diffusion processes, domain growth, aging phenomena.
      Interestingly, while local observables, being controlled by the largest
      wavelength fluctuations, seem to suggest a purely diffusive behavior, the
      formation of spatially extended structures and topological defects, such as
      vortices and shocks, reveals a more complex scenario. Finally, only for
      quasielastic systems, we observe a neat scale separation, which represents a
      fundamental hypothesis to develop a granular hydrodynamics.

PMID- 12059546
TI  - Shear profiles and localization in simulations of granular materials.
AB  - We present results from two-dimensional computer simulations of shearing granular
      layers, using a discrete element code, and applying a wide range of boundary
      conditions. We specifically investigate the distribution of shear within the
      granular layer and find two different modes of localization depending on the
      applied shear velocity, pressure, and layer thickness: (1) granular layers that
      develop a persistent shearing boundary region ("fluidlike" behavior) and (2)
      layers that switch between diffuse deformation and randomly positioned internal
      shear bands ("solidlike" behavior). The two end-member deformation modes can be
      found in laboratory experiments performed under low and high confining pressure,
      respectively. Micromechanical investigation reveals two different statistical
      distributions of the grain contacts correlating with the two different shearing
      modes. These results imply that rehological transitions in granular flow modes
      are linked to quantifiable microtstructural organization.

PMID- 12059547
TI  - Diffusion in a granular fluid. I. Theory.
AB  - Many important properties of granular fluids can be represented by a system of
      hard spheres with inelastic collisions. Traditional methods of nonequilibrium
      statistical mechanics are effective for analysis and description of the inelastic
      case as well. This is illustrated here for diffusion of an impurity particle in a
      fluid undergoing homogeneous cooling. An appropriate scaling of the Liouville
      equation is described such that the homogeneous cooling ensemble and associated
      time correlation functions map to those of a stationary state. In this form the
      familiar methods of linear response can be applied, leading to Green-Kubo and
      Einstein representations of diffusion in terms of the velocity and mean-square
      displacement correlation functions. These correlation functions are evaluated
      approximately using a cumulant expansion and from kinetic theory, providing the
      diffusion coefficient as a function of the density and the restitution
      coefficients. Comparisons with results from molecular-dynamics simulation are
      given in the following companion paper.

PMID- 12059548
TI  - Diffusion in a granular fluid. II. Simulation.
AB  - The linear-response description for impurity diffusion in a granular fluid
      undergoing homogeneous cooling is developed in the preceding paper. The formally
      exact Einstein and Green-Kubo expressions for the self-diffusion coefficient are
      evaluated there from an approximation to the velocity autocorrelation function.
      These results are compared here to those from molecular-dynamics simulations over
      a wide range of density and inelasticity, for the particular case of self
      diffusion. It is found that the approximate theory is in good agreement with
      simulation data up to moderate densities and degrees of inelasticity. At higher
      density, the effects of inelasticity are stronger, leading to a significant
      enhancement of the diffusion coefficient over its value for elastic collisions.
      Possible explanations associated with an unstable long wavelength shear mode are
      explored, including the effects of strong fluctuations and mode coupling.

PMID- 12059549
TI  - Mean-field model of free-cooling inelastic mixtures.
AB  - We consider a mean-field model describing the free-cooling process of a two
      component granular mixture, a generalization of the so called scalar Maxwell
      model. The cooling is viewed as an ordering process and the scaling behavior is
      attributed to the presence of an attractive fixed point at v=0 for the dynamics.
      By means of asymptotic analysis of the Boltzmann equation and of numerical
      simulations we get the following results: (1) we establish the existence of two
      different partial granular temperatures, one for each component, which violates
      the zeroth law of thermodynamics; (2) we obtain the scaling form of the two
      distribution functions; (3) we prove the existence of a continuous spectrum of
      exponents characterizing the inverse-power-law decay of the tails of the
      velocity, which generalizes the previously reported value of 4 for the pure
      model; (4) we find that the exponents depend on the composition, masses, and
      restitution coefficients of the mixture; (5) we also remark that the reported
      distributions represent a dynamical realization of those predicted by the
      nonextensive statistical mechanics, in spite of the fact that ours stem from a
      purely dynamical approach.

PMID- 12059550
TI  - Force correlations in the q model for general q distributions.
AB  - We study force correlations in the q model for granular media at infinite depth
      for general q distributions. We show that there are no two-point force
      correlations as long as q values at different sites are uncorrelated. However,
      higher-order correlations can persist, and if they do, they only decay with a
      power of the distance. Furthermore, we find the entire set of q distributions for
      which the force distribution factorizes. It includes distributions ranging from
      infinitely sharp to almost critical. Finally, we show that two-point force
      correlations do appear whenever there are correlations between q values at
      different sites in a layer; various cases are evaluated explicitly.

PMID- 12059551
TI  - Analogies between granular jamming and the liquid-glass transition.
AB  - Based on large-scale, three-dimensional chute flow simulations of granular
      systems, we uncover strong analogies between the jamming of the grains and the
      liquid-glass transition. The angle of inclination theta in the former transition
      appears as an analog of temperature T in the latter. The transition is manifested
      in the development of a plateau in the contact normal force distribution P(f) at
      small forces, the splitting of the second peak in the pair-correlation function
      g(r), and increased fluctuations of the system energy. The static state also
      exhibits history dependence, akin to the quench-rate dependence of structural
      properties of glasses, due to the hyperstaticity of the contact network.

PMID- 12059552
TI  - Transport with multiple-rate exchange in disordered media.
AB  - We investigate transport of particles subject to exchange using the continuous
      time random-walk framework. Transition is controlled by macroscale, and exchange
      by both macroscale and microscale disorder. A wide class of exchange mechanisms
      is represented using the multiple-rate exchange model. Particles are transported
      along random trajectories viewed as one-dimensional lattices. The solution of the
      transport problem is obtained in the form of the crossing-time density, h(t;L),
      at an exit surface L; h is dependent on two functions, g and f. g characterizes
      exchange controlled by microscale disorder. The joint density f is central for
      the solution as it relates the microscale and macroscale disorder along random
      trajectories. For the case of transition and exchange disorder, we show that
      power-law exponent eta (characterizing microscale disorder) and power-law
      exponents alpha(tau) and alpha(mu) (characterizing macroscale disorder), define
      two regions delimited by a line alpha(tau)=alpha(mu)(eta+1): One in which the
      asymptotic transport is dominated by transition, and one in which it is dominated
      by the exchange. For the case of transition disorder with uniform exchange, both
      transition and exchange can influence the late-time behavior of h(t). Microscale
      exchange processes will unconditionally influence the late-time behavior of h(t)
      only if eta<0. If eta>0, exchange will dominate at late time provided that
      transition is asymptotically Gaussian.

PMID- 12059553
TI  - Probing the internal field gradients of porous media.
AB  - We devise a modified Carr-Purcell-Meiboom-Gill pulse sequence that allows us to
      probe the apparent internal field gradient distribution of a fluid-saturated
      porous medium as a function of the pore size. This distribution is displayed as a
      two-dimensional map with one axis being the field gradient, another axis being
      the T2 relaxation time reflecting different pore sizes, and the vertical
      amplitudes being proportional to the proton population. Such a scheme of two
      dimensional representation for fluid-saturated porous media can also be used for
      the identification of pore fluids using the contrast of their diffusion
      coefficients.

PMID- 12059554
TI  - Square to stripe transition and superlattice patterns in vertically oscillated
      granular layers.
AB  - We investigated the physical mechanism for the pattern transition from square
      lattice to stripes, which appears in vertically oscillating granular layers. We
      present a continuum model to show that the transition depends on the competition
      between inertial force and local saturation of transport. By introducing multiple
      free-flight times, this model further enables us to analyze the formation of
      superlattices as well as hexagonal lattices

PMID- 12059555
TI  - Kinetics of growth process controlled by convective fluctuations.
AB  - A model of the spherical (compact) growth process controlled by a fluctuating
      local convective velocity field of the fluid particles is introduced. It is
      assumed that the particle velocity fluctuations are purely noisy, Gaussian, of
      zero mean, and of various correlations: Dirac delta, exponential, and algebraic
      (power law). It is shown that for a large class of the velocity fluctuations, the
      long-time asymptotics of the growth kinetics is universal (i.e., it does not
      depend on the details of the statistics of fluctuations) and displays the power
      law time dependence with the classical exponent 1/2 resembling the diffusion
      limited growth. For very slow decay of algebraic correlations of fluctuations
      asymptotically like t(-gamma), gamma in (0,1]), kinetics is anomalous and depends
      strongly on the exponent gamma. For the averaged radius of the crystal <R(t)>
      approximately t(1-gamma/2) for 0<gamma<1 or <R(t)> approximately (t ln t)1/2 for
      gamma=1.

PMID- 12059556
TI  - Thixotropy in macroscopic suspensions of spheres.
AB  - An experimental study of the viscosity of a macroscopic suspension, i.e., a
      suspension for which Brownian motion can be neglected, under steady shear is
      presented. The suspension is prepared with a high packing fraction and is density
      matched in a Newtonian carrier fluid. The viscosity of the suspension depends on
      the shear rate and the time of shearing. It is shown that a macroscopic
      suspension shows thixotropic viscosity, i.e., shear thinning with a long
      relaxation time as a unique function of shear. The relaxation times show a
      systematic decrease with increasing shear rate. These relaxation times are larger
      when decreasing the shear rates, compared to those observed after increasing the
      shear. The time scales involved are about 10 000 times larger than the viscous
      time scale tau(visc)=a2/nu and about 1000 times smaller than the thermodynamic
      time scale tau(therm)=Pe/gamma. (a is the gap width of the viscometer, nu is the
      kinematic viscosity, Pe=6pi(eta)gamma;tau)3/(k(B)T) is the Peclet number and
      gamma; is the shear rate.) The structure of the suspension at the outer cylinder
      of a viscometer is monitored with a camera, showing the formation of a hexagonal
      structure. The temporal decrease of the viscosity under shear coincides with the
      formation of this hexagonal pattern.

PMID- 12059557
TI  - Diffusing wave spectroscopy and small-angle neutron scattering from concentrated
      colloidal suspensions.
AB  - We have studied the properties of dense colloidal suspensions with a combination
      of small-angle neutron scattering (SANS) and diffusing wave spectroscopy (DWS).
      Contrary to single light scattering, DWS provides dynamic information on length
      scales, from 1 to 100 nm, comparable to SANS. This offers a unique range of
      accessible length and time scales perfectly suited for the (noninvasive)
      investigation of highly concentrated systems. By this we obtain valuable
      information about the structural properties and the short-time diffusion of
      electrostatically stabilized, but strongly screened, hard-sphere-like colloidal
      suspensions with volume fractions up to 30%. We furthermore discuss the
      consequences of local structural ordering on the optical properties, such as
      optical density and polarization. Quantitative agreement is found when comparing
      transmission measurements (optical density) with parameter-free numerical
      calculations based on the structural characterization from SANS.

PMID- 12059558
TI  - Shape of the liquid-vapor coexistence curve for temperature and density dependent
      effective interactions.
AB  - The asymmetry of the coexistence curve that is observed in several micellar
      systems is discussed in relation with the dependence of the effective interaction
      on temperature and density. Standard results for the diameter of the coexistence
      curve in the van der Waals theory are generalized so as to deal with this
      combined dependence. The qualitative trends so deduced are assessed by comparison
      with coexistence curves of Yukawa fluids computed with integral equation
      theories. The role of the variables used to plot the coexistence curve and the
      nonlinear behavior of its diameter beyond the critical region are discussed in
      relation with the decrease of the interaction strength with density. The
      possibility of using the asymmetry of the coexistence curve as an indicator of
      the state dependence of the effective interaction is finally discussed.

PMID- 12059559
TI  - Charge fluctuations and counterion condensation.
AB  - We predict a condensation phenomenon in an overall neutral system, consisting of
      a single charged plate and its oppositely charged counterions. Based on the "two
      fluid" model, in which the counterions are divided into a "free" and a
      "condensed" fraction, we argue that for high surface charge, fluctuations can
      lead to a phase transition in which a large fraction of counterions is condensed.
      Furthermore, we show that depending on the valence, the condensation is either a
      first-order or a smooth transition.

PMID- 12059560
TI  - Brillouin-scattering study of propylene carbonate: an evaluation of
      phenomenological and mode coupling analyses.
AB  - Brillouin-scattering spectra of the molecular glass-forming material propylene
      carbonate (PC) in the temperature range 140 K to 350 K were analyzed using both
      the phenomenological Cole-Davidson memory function and a hybrid memory function
      consisting of the Cole-Davidson function plus a power-law term representing the
      critical decay part of the fast beta relaxation. The spectra were also analyzed
      using the extended two-correlator schematic mode-coupling theory (MCT) model
      recently employed by Gotze and Voigtmann to analyze depolarized light
      backscattering, dielectric, and neutron-scattering spectra of PC [Phys. Rev. E
      61, 4133 (2000)]. We assess the ability of the phenomenological and MCT fits,
      each with three free fitting parameters, to simultaneously describe the spectra
      and give reasonable values for the alpha-relaxation time tau(alpha).

PMID- 12059561
TI  - Kinetic theory for flows of nonhomogeneous rodlike liquid crystalline polymers
      with a nonlocal intermolecular potential.
AB  - The Doi kinetic theory for flows of homogeneous, rodlike liquid crystalline
      polymers (LCPs) is extended to model flows of nonhomogeneous, rodlike LCPs
      through a nonlocal (long-range) intermolecular potential. The theory features (i)
      a nonlocal, anisotropic, effective intermolecular potential in an integral form
      that is consistent with the chemical potential, (ii) short-range elasticity as
      well as long-range isotropic and anisotropic elasticity, (iii) a closed-form
      stress expression accounting for the nonlocal molecular interaction, and (iv) an
      extra elastic body force exclusively associated with the integral form of the
      intermolecular potential. With the effective intermolecular potential, the theory
      is proven to be well posed in that it warrants a positive entropy production and
      thereby the second law of thermodynamics. Approximate theories are obtained by
      gradient expansions of the number density function in the free energy density.

PMID- 12059562
TI  - Microrheology of polyethylene oxide using diffusing wave spectroscopy and single
      scattering.
AB  - Experiments investigating the local viscoelastic properties of a simple uncross
      linked flexible polymer are performed on polyethylene oxide solutions in the
      semidilute regime using polystyrene beads of varying sizes and surface chemistry
      as probes. We measure the thermal motions of the beads to obtain the elastic and
      viscous moduli of our sample. Two different dynamic light scattering techniques,
      diffusing wave spectroscopy and quasielastic light scattering (QELS), are used to
      determine the dynamics of the probe particles. Diffusing wave spectroscopy probes
      the short time dynamics of the scatterers while QELS or single scattering
      measures the dynamics at larger times. This results in a larger frequency overlap
      of the data obtained from the microrheological techniques with the data obtained
      from the conventional bulk measurements. The moduli are estimated using a
      modified algebraic form of the generalized Stokes-Einstein equation. Comparison
      of microrheology with bulk measurements shows excellent similarity confirming the
      applicability of this method for simple, uncross-linked polymeric systems.

PMID- 12059563
TI  - Anomalous stretching in a simple glass-forming liquid.
AB  - The frequency dependent shear modulus G(omega) for a simple liquid shows strongly
      stretched behavior and the stretching exponent increases with decrease of
      temperature. This unconventional behavior was reported earlier in Phys. Rev.
      Lett. 73, 963 (1994) from experiments on simple liquids. We demonstrate here that
      this is a feature of the characteristic two-step relaxation process of the self
      consistent mode coupling theory of supercooled liquids.

PMID- 12059564
TI  - Observation of single molecule transport at surfaces via scanning microscopies:
      Monte Carlo wave function study of a model problem.
AB  - We discuss experiments where the trajectories of individual molecules or atoms at
      surfaces are observed by means of scanning microscopy. A scanning probe moves
      along the surface and excites the molecule so that the molecule's location is
      deduced from the times at which fluorescence photons are emitted. Operation of
      other types of scanning microscopes can be described by similar models. The
      observed trajectories are inherently affected by the interaction between the
      molecule and the probe such that the measured diffusion coefficient depends on
      the frequency at which the surface is scanned. The number of photons emitted by
      the molecule during a scan is affected in a nontrivial way by its mobility. If
      photoexcitation increases the mobility, we find emission to be suppressed.

PMID- 12059565
TI  - Chemical influences on adsorption-mediated self-propelled drop movement.
AB  - We report studies of reactive wetting employing droplets of a nonpolar liquid
      (decahydronaphthalene) on chemically patterned surfaces. The drops contain an n
      alkylamine that adsorbs onto surfaces exposing carboxylic acid groups and
      produces surfaces exposing methyl groups. The change in surface energy that
      occurs concurrent with the formation of an oriented monomolecular film of
      alkylamine during this process is sufficient to produce a self-propelled movement
      of decahydronaphthalene drops on the surface. We employed patterning to direct
      the movement of the drops on the surface, thereby allowing measurements of the
      relationships between the macroscopic fluidic behavior of the droplets and
      microscopic adsorption events. Specifically, we examined the effects of the
      unbalanced surface-tension force and the influences of adsorbate concentration on
      drop movement. In this latter case, both kinetic and thermodynamic arguments can
      be applied to describe the system. We compared the predictions from these two
      approaches by analyzing data from the present system and those reported by F.
      Domingues Dos Santos and T. Ondarcuhu [Phys. Rev. Lett. 75(16), 2972 (1975)] that
      exhibited opposite trends in behavior. The present analysis provides insight into
      the influence of chemical reaction kinetics on adsorption-mediated drop movement
      (i.e., reactive wetting).

PMID- 12059566
TI  - Experimental evidence for an original two-dimensional phase structure: an
      antiparallel semifluorinated monolayer at the air-water interface.
AB  - We show the spontaneous formation of an antiparallel monolayer of diblock
      semifluorinated n-alkane molecules spread at the air-water interface. We used
      simultaneous measurements of surface pressure and surface potential versus
      molecular area and performed grazing x-ray reflectivity experiments to
      characterize the studied monolayer, which is obtained at almost zero surface
      pressure and precedes the formation of a bilayer at higher surface pressure. Its
      thickness, equal to 2.7 nm, was found to be independent of the molecular area.
      This behavior may be explained by van der Waals and electrostatic interactions.

PMID- 12059567
TI  - Free growth and instability morphologies in directional melting of alloys.
AB  - The dynamics of melting morphologies, namely, liquid droplets in the bulk solid
      and liquid dendrites due to morphological instability of the phase boundary, is
      observed in situ and in real time during directional melting of transparent
      succinonitrile-acetone alloys in a cylinder. Specific patterns are associated to
      grain boundaries. A model based on free growth but with time-dependent
      superheating is proposed for the lateral growth of the liquid inclusions.
      Contrary to what is largely believed, it is shown that free melting is not the
      mere reversal of free crystal growth, basically because solute diffusion is much
      lower in the solid, which imposes a boundary layer approach.

PMID- 12059568
TI  - Buoyancy-driven instability of an autocatalytic reaction front in a Hele-Shaw
      cell.
AB  - An autocatalytic reaction-diffusion front between two reacting species may
      propagate as a solitary wave, namely, at constant velocity and with a stationary
      concentration profile. Recent experiments on such reactions have been reported to
      be buoyancy unstable, under certain conditions. We calculate the linear
      dispersion relation of the resulting instability, by applying our recent analysis
      of the Rayleigh-Taylor instability of two miscible fluids in a Hele-Shaw cell.
      The computed dispersion relation as well as our three-dimensional lattice
      Bhatnagar-Gross-Krook (BGK) simulations fit reasonably well experimental growth
      rates reported previously.

PMID- 12059569
TI  - Growth pulsations in symmetric dendritic crystallization in thin polymer blend
      films.
AB  - The crystallization of polymeric and metallic materials normally occurs under
      conditions far from equilibrium, leading to patterns that grow as propagating
      waves into the surrounding unstable fluid medium. The Mullins-Sekerka instability
      causes these wave fronts to break up into dendritic arms, and we anticipate that
      the normal modes of the dendrite tips have a significant influence on pattern
      growth. To check this possibility, we focus on the dendritic growth of
      polyethylene oxide in a thin-film geometry. This crystalline polymer is mixed
      with an amorphous polymer (polymethyl-methacrylate) to "tune" the morphology and
      clay was added to nucleate the crystallization. The tips of the main dendrite
      trunks pulsate during growth and the sidebranches, which grow orthogonally to the
      trunk, pulsate out of phase so that the tip dynamics is governed by a limit
      cycle. The pulsation period P increases sharply with decreasing film thickness L
      and then vanishes below a critical value L(c) approximately 80 nm. A change of
      dendrite morphology accompanies this transition.

PMID- 12059570
TI  - Transition from gravito- to electroconvective regimes in thin-layer
      electrodeposition.
AB  - The transition from gravitoconvective to electroconvective prevailing regimes in
      thin-layer electrochemical deposition is analyzed through variations of
      electrolyte viscosity at constant cell thickness. The distribution of velocity
      directions at the deposit front is a measure of the relative weight of
      electroconvection versus gravitoconvection, and a signature of that transition.
      The experiments are carried out under galvanostatic conditions in convection
      prevailing regimes. Particle image velocimetry reveals that at low viscosities,
      buoyancy driven convection dominates; as viscosity increases, electrically driven
      convection becomes more important, eventually prevailing. The transition is
      observed at 1.5 times the viscosity of water. The theoretical model presented
      reveals that an increase of the Poisson and Reynolds numbers and a decrease of
      the Peclet and electric Grashof numbers, when viscosity increases, makes the
      electroconvective motion relatively more important. The model predicts a
      transition at approximately two times the viscosity of water. We may conclude
      that, in a physicochemical hydrodynamic flow involving ions, under galvanostatic
      conditions, increasing viscosity damps gravitoconvection and enhances
      electroconvection.

PMID- 12059571
TI  - Flow dissipation effects in a nonlinear nematic fiber.
AB  - Dissipative effects due to the presence of hydrodynamic flow in a cylindrical
      fiber whose cladding is an initially quiescent incompressible nematic liquid
      crystal are analyzed. An analytic and iterative solution of the nematodynamic
      equations coupled to the Maxwell's equations describing the propagation of a
      narrow wave packet of transverse magnetic modes is provided. We derive a
      generalized nonlinear Schroedinger equation for the amplitude of this propagating
      wave packet that takes into account the dissipation in the nematic's
      reorientation and the hydrodynamical effects. For the solitonlike solution of
      this equation we find that the penetration length and the real part of the
      nonlinear refraction index increase by a factor of 1.75, with respect to those
      values obtained in the absence of hydrodynamical flow. The imaginary part remains
      unaltered.

PMID- 12059572
TI  - Diffusion in a smectic liquid crystal with screw dislocations.
AB  - Screw dislocations provide barrier-free pathways that enhance interlayer
      diffusion in smectic liquid crystals and other layered materials. To explore this
      contribution to interlayer diffusion we study a "random parking garage" model in
      which a random walker can move between layers only by circling a dislocation
      core. We find that in such a layered system with a density of rho screw
      dislocations per unit area, with randomly chosen position, Burgers vector and
      phase, the ratio of interlayer to intralayer diffusion coefficients is
      D//D(perpendicular)=(rho(b2)/4pi)ln R/a. Here b is the layer spacing, R is the
      layer radius, and a is the dislocation core size. Monte Carlo simulations are in
      agreement with this result. We discuss implications for both molecular simulation
      and experimental studies of diffusion in smectics.

PMID- 12059573
TI  - Polymer network-induced ordering in a nematogenic liquid: a Monte Carlo study.
AB  - In this Monte Carlo study we investigate molecular ordering in a nematogenic
      liquid with dispersed polymer networks. The polymer network fibers are assumed to
      have rough surface morphology resulting in a partial randomness in anchoring
      conditions, while the fiber direction is assumed to be well defined. In
      particular, we focus on the loss of long-range aligning capability of the network
      when the degree of disorder in anchoring is increased. This process is monitored
      by calculating relevant order parameters and the corresponding 2H nuclear
      magnetic resonance spectra, showing that the aligning ability of the network is
      lost only for completely disordering anchoring conditions. Moreover, above the
      nematic-isotropic transition temperature surface-induced paranematic order is
      detected. In addition, for perfectly smooth fiber surfaces with homeotropic
      anchoring conditions topological line defects can be observed.

PMID- 12059574
TI  - Evolution of photonic structure on deformation of cholesteric elastomers.
AB  - We subject a monodomain cholesteric liquid crystal elastomer to uniaxial strain
      perpendicular to its helical axis and study the response of its texture to
      deformation. A combination of mechanical, optical, and x-ray scattering
      measurements confirms the prediction for the director rotation, coarsening, and
      then unwinding the cholesteric helix. The study of optical absorption of
      circularly polarized light quantifies the complex dependence of the photonic band
      gap structure on strain and directly relates to the microscopic deformation of
      elastomer. Agreement is found with the recently proposed theoretical prediction
      of the photonic structure of cholesteric elastomers.

PMID- 12059575
TI  - Pressure effect on the smectic-A-isotropic phase transition.
AB  - We examine the effect of pressure on the smectic-A-isotropic phase transition
      within the Landau phenomenological theory. The influence of pressure on the
      smectic-A-isotropic phase transition is discussed by varying the coupling between
      the orientational and the translational order parameter. The transition is found
      to be of first order even at elevated pressure. The pressure dependence nonlinear
      dielectric effect in the isotropic phase of the smectic-A-isotropic transition is
      calculated. The theoretical results are in good qualitative agreement with
      available experimental results.

PMID- 12059576
TI  - Computer simulation of apolar bent-core and rodlike molecules.
AB  - Bent-core molecules have received much interest due to their biaxiality and novel
      phase ordering. It is, therefore, of interest to model the characteristic shape
      of these molecules and observe the effect on liquid crystal mesophase formation
      in a computer simulation study. A simple model of the interaction employed a two
      site Gay-Berne potential with the sites separated by +/-0.5 reduced units for all
      models. The angle between the two sites, 180 degrees -gamma, was varied from
      gamma=0 degrees to gamma=70 degrees and influenced the phase behavior markedly.
      The rodlike model formed isotropic, nematic, smectic-A, and smectic-B, phases.
      Results for the bent-core models show that as the angle gamma increases the
      transition temperature to the ordered phase decreases. As gamma increases the
      nematic phase is first destabilized then stabilized with respect to the smectic
      phase and a tilted smectic-B phase is seen at gamma=20 degrees. For gamma=40
      degrees a "TGB-like" phase is identified as the system cools whereas for gamma=70
      degrees no ordered phase is formed.

PMID- 12059577
TI  - Uniaxial and biaxial soft deformations of nematic elastomers.
AB  - We give a geometric interpretation of the soft elastic deformation modes of
      nematic elastomers, with explicit examples, for both uniaxial and biaxial nematic
      order. We show the importance of body rotations in this nonclassical elasticity
      and how the invariance under rotations of the reference and target states gives
      soft elasticity (the Golubovic and Lubensky theorem). The role of rotations makes
      the polar decomposition theorem vital for decomposing general deformations into
      body rotations and symmetric strains. The role of the square roots of tensors and
      that of finding explicit forms for soft deformations (the approach of Olmsted)
      are discussed in this context.

PMID- 12059578
TI  - Experimental study of coarsening dynamics of the zigzag wall in a nematic liquid
      crystal with negative dielectric anisotropy.
AB  - When a homeotropically aligned nematic liquid crystal cell is placed above two
      permanent magnets forming a magnetic quadrupole, a straight splay-bend wall, or a
      so-called Ising wall, is formed. With a material of positive dielectric
      anisotropy, it has been shown that the application of an electric field
      perpendicular to the plates leads to a zigzag instability of the wall,
      exclusively related to the elastic anisotropy of the liquid crystal. In this
      case, the coarsening process of the zigzag is very slow, which in turn leads to
      experimental difficulties concerning its quantitative investigation. If a
      material of negative dielectric anisotropy is used under an electric field with
      low voltage and low frequency, two convective rolls appear along the Ising wall
      due to the charge focusing effect, which is also responsible, at a higher voltage
      in the homogenous tilted regions, for the appearance of Williams domains
      electrohydrodynamic instability. If the voltage is higher than a threshold value,
      the straight Ising wall spontaneously breaks into a zigzag shape and a fast
      coarsening of the zigzag proceeds, associated with the annihilation of two
      neighboring vertices. In the present paper, the coarsening dynamics of this
      system, which can be considered as a one-dimensional Ising situation, are
      investigated experimentally. At late times, the average width of the zigzag
      increases logarithmically with time. This finding is consistent with the theory
      and also with the numerical simulation of a one-dimensional Cahn-Hilliard
      situation having a conserved order parameter. The scaling analysis of size
      distribution of the Ising domain, the shape of the power spectrum, and of the
      correlation function of the Ising order parameter, as well as the number density
      correlation functions of kinks also confirms that the dynamical scaling law
      predicted for one-dimensional conservative systems holds for the coarsening
      process. As supposed from symmetry arguments, it is confirmed that this
      experiment constitutes a one-dimensional analog of spinodal decomposition.

PMID- 12059579
TI  - Parametrization and validation of a force field for liquid-crystal forming
      molecules.
AB  - First principles density functional calculations have been carried out to
      determine the structures and conformational energies of a series of liquid
      crystal fragment molecules. The calculations have been used to derive a molecular
      mechanics force field that describes a subset of commonly occurring liquid
      crystal molecules. The force field has been used to carry out molecular dynamics
      simulations of the bulk phase for these fragment molecules. Computed densities
      and heats of vaporization are in good agreement with experimental data. These
      results should be useful in future molecular dynamics simulations of liquid
      crystal systems.

PMID- 12059580
TI  - Flexoelectric switching in a bistable nematic device.
AB  - We present a continuum theory model of switching in a bistable nematic liquid
      crystal device. The bistability of the device investigated relies on the fact
      that one of the cell surfaces exhibits two stable anchoring states, that is, two
      surface director orientations are locally stable. Since the other surface
      exhibits monostable, homeotropic anchoring there are two possible ground state
      director orientations within the cell, depending on the director orientation at
      the bistable surface. We first investigate the stability of these base states and
      find a critical surface anchoring strength below which only one of the states is
      stable. We also investigate the process of switching between the two stable
      states through the application of an electric field and the presence of a
      flexoelectric polarization. At high field strengths the dielectric interaction
      with the applied field will dominate the flexoelectric effect and may hinder
      switching. We find, therefore, that a window of possible field strengths exists
      within which switching occurs.

PMID- 12059581
TI  - Surface effects on the amplitude of fluctuation-induced interactions in smectic
      films.
AB  - Within a quadratic functional integral approach, we investigate the role played
      by surface terms in the fluctuation-induced surface-surface interaction of free
      standing smectic liquid crystals. We show that the typical 1/l decay of the
      Casimir-type contribution to the free energy of a film with thickness l is
      replaced by a faster 1/l3 decay at a characteristic surface tension. An
      intermediate 1/l2 decay can also take place for specific surface parameters with
      unlike boundary conditions. In all the investigated cases, a repulsive long-range
      force appears only for mixed boundary conditions with strong anchoring at one
      surface and weak anchoring at the opposite one. Further, the amplitude of the
      thermal Casimir energy, besides being influenced by the applied surface tension,
      depicts a nonmonotonic dependence on the coupling between the outermost film
      layers, reflecting a crossover between strong and weak anchoring regimes.

PMID- 12059582
TI  - Statistical thermodynamics of equilibrium polymers at interfaces.
AB  - The behavior of a solution of equilibrium polymers (or living polymers) at an
      interface is studied, using a Bethe-Guggenheim lattice model for molecules with
      orientation dependent interactions. The density profile of polymers and the chain
      length distribution are calculated. For equilibrium polymers at a nonadsorbing
      surface it is found that the depletion layer thickness has a maximum. In dilute
      solutions it is proportional to the average radius of gyration of the polymers,
      which increases with increasing concentration. Above the overlap concentration it
      corresponds to the bulk correlation length, which decreases with increasing
      concentration. Furthermore, it is found that the surface region is predominantly
      occupied by the shorter chains. Both in dilute solutions and in a melt of
      equilibrium polymers, a very simple relation is found between the surface excess
      of a component and the chain length.

PMID- 12059583
TI  - Finite-size and asymptotic behaviors of the gyration radius of knotted
      cylindrical self-avoiding polygons.
AB  - Several nontrivial properties are shown for the mean-square radius of gyration
      R2(K) of ring polymers with a fixed knot type K. Through computer simulation, we
      discuss both finite size and asymptotic behaviors of the gyration radius under
      the topological constraint for self-avoiding polygons consisting of N cylindrical
      segments with radius r. We find that the average size of ring polymers with the
      knot K can be much larger than that of no topological constraint. The effective
      expansion due to the topological constraint depends strongly on the parameter r
      that is related to the excluded volume. The topological expansion is particularly
      significant for the small r case, where the simulation result is associated with
      that of random polygons with the knot K.

PMID- 12059585
TI  - Pattern formation and coarsening during metastable phase separation in lysozyme
      solutions.
AB  - We observed interesting structures during phase transformations of lysozyme
      solutions. The process begins with the separation of a protein-rich liquid phase
      in the form of droplets. The droplets fall to the bottom of the chamber in a few
      minutes, and on the scale of an hour they begin to merge, forming an
      interconnected spongelike structure. In the final transformation process, the
      sponge turns into crystals. The existence of the sponge phase depends upon the
      relative time scales for droplet coalescence and crystal nucleation, something we
      were able to vary by changing the salt concentration in our solution. We expect
      our observations to have significance for producing protein crystals for x-ray
      structure analysis of proteins.

PMID- 12059584
TI  - Intermediate length scale dynamics of polyisobutylene.
AB  - We report on a neutron spin echo investigation of the intermediate scale dynamics
      of polyisobutylene studying both the self-motion and the collective motion. The
      momentum transfer (Q) dependences of the self-correlation times are found to
      follow a Q(-2/beta) law in agreement with the picture of Gaussian dynamics. In
      the full Q range of observation, their temperature dependence is weaker than the
      rheological shift factor. The same is true for the stress relaxation time as seen
      in sound wave absorption. The collective times show both temperature dependences;
      at the structure factor peak, they follow the temperature dependence of the
      viscosity, but below the peak, one finds the stress relaxation behavior.

PMID- 12059586
TI  - Competition of mesoscales and crossover to tricriticality in polymer solutions.
AB  - We show that the approach to asymptotic fluctuation-induced critical behavior in
      polymer solutions is governed by a competition between a correlation length
      diverging at the critical point and an additional mesoscopic length-scale, the
      radius of gyration. Accurate light scattering experiments on polystyrene
      solutions in cyclohexane with polymer molecular weights ranging from 200 000 up
      to 11.4x10(6) clearly demonstrate a crossover between two universal regimes: a
      regime with Ising asymptotic critical behavior, where the correlation length
      prevails, and a regime with tricritical theta-point behavior determined by a
      mesoscopic polymer-chain length.

PMID- 12059587
TI  - Impact of regulatory proteins on the nonlinear dynamics of DNA.
AB  - In this paper we examine the nonlinear dynamics of a DNA chain whose exciton
      modes are affected by regulatory proteins that may become bound to the DNA chain
      by hydrogen bonds. The dynamics of the DNA chain is described by the Peyrard
      Bishop model. Since this model gives rise to large-amplitude broad oscillations
      of base pairs, we consider the impact of attached regulatory proteins on the so
      called breathers or bubbles. Assuming that an ideal gas of bubbles may exist in
      the DNA chain at physiological temperatures we adopt a statistical approach to
      calculate the average size of base-pair stretching under the prevailing
      conditions.

PMID- 12059588
TI  - Considerations in phase plane analysis for nonstationary reentrant cardiac
      behavior.
AB  - Cardiac reentrant arrhythmias may be examined by using time-series analysis,
      where a state variable is plotted against the same variable with an embedded time
      delay tau to form a phase portrait. The success of this procedure is contingent
      upon the resultant phase-space trajectories encircling a fixed origin. However,
      errors in interpreting the dynamics of phase singularities associated with
      reentry may arise due to the trajectories not encircling the origin or due to a
      poor choice of tau. We demonstrate an algorithm which is capable of establishing
      proper orbits without the need to specify tau. We find that phase singularities
      could be localized closer to the point of initial formation than was possible
      previously, which is important for the purposes of singularity tracking and
      investigating electrodynamic interactions.

PMID- 12059589
TI  - Submillimeter-wave phonon modes in DNA macromolecules.
AB  - A detailed investigation of phonon modes in DNA macromolecules is presented. This
      work presents experimental evidence to confirm the presence of multiple
      dielectric resonances in the submillimeter-wave spectra (i.e., approximately 0.01
      10 THz) obtained from DNA samples. These long-wave (i.e., approximately 1-30 cm(
      1)) absorption features are shown to be intrinsic properties of the particular
      DNA sequence under study. Most importantly, a direct comparison of spectra
      between different DNA samples reveals a large number of modes and a reasonable
      level of sequence-specific uniqueness. This work establishes the initial
      foundation for the future use of submillimeter-wave spectroscopy in the
      identification and characterization of DNA macromolecules.

PMID- 12059590
TI  - Nonlinear dynamics of direction-selective recurrent neural media.
AB  - The direction selectivity of cortical neurons can be accounted for by asymmetric
      lateral connections. Such lateral connectivity leads to a network dynamics with
      characteristic properties that can be exploited for distinguishing in
      neurophysiological experiments this mechanism for direction selectivity from
      other possible mechanisms. We present a mathematical analysis for a class of
      direction-selective neural models with asymmetric lateral connections.
      Contrasting with earlier theoretical studies that have analyzed approximations of
      the network dynamics by neglecting nonlinearities using methods from linear
      systems theory, we study the network dynamics with nonlinearity taken into
      consideration. We show that asymmetrically coupled networks can stabilize
      stimulus-locked traveling pulse solutions that are appropriate for the modeling
      of the responses of direction-selective neurons. In addition, our analysis shows
      that outside a certain regime of stimulus speeds the stability of these solutions
      breaks down, giving rise to lurching activity waves with specific spatiotemporal
      periodicity. These solutions, and the bifurcation by which they arise, cannot be
      easily accounted for by classical models for direction selectivity.

PMID- 12059591
TI  - Chaos in two-loop negative feedback systems.
AB  - Multiloop delayed negative feedback systems, with each feedback loop having its
      own characteristic time lag (delay), are used to describe a great variety of
      systems: optical systems, neural networks, physiological control systems, etc.
      Previous investigations have shown that if the number of delayed feedback loops
      is greater than two, the system can exhibit complex dynamics and chaos, but in
      the case of two delayed loops only periodic solutions were found. Here we show
      that a period-doubling cascade and chaotic dynamics are also found in systems
      with two coupled delayed negative feedback loops.

PMID- 12059592
TI  - Array-enhanced coherence resonance and forced dynamics in coupled FitzHugh-Nagumo
      neurons with noise.
AB  - Nonlinear dynamics of coupled FitzHugh-Nagumo neurons subject to independent
      noise is analyzed. A kind of self-sustained global oscillation with almost
      synchronous firing is generated by array-enhanced coherence resonance. Further,
      forced dynamics of the self-sustained global oscillation stimulated by sinusoidal
      input is analyzed and classified as synchronized, quasiperiodic, and chaotic
      responses just like the forced oscillations in nerve membranes observed by in
      vitro experiments with squid giant axons. Possible physiological importance of
      such forced oscillations is also discussed.

PMID- 12059593
TI  - Structural changes of pulled vesicles: a Brownian dynamics simulation.
AB  - We studied the structural changes of bilayer vesicles induced by mechanical
      forces using a Brownian dynamics simulation. Two nanoparticles, which interact
      repulsively with amphiphilic molecules, are put inside a vesicle. The position of
      one nanoparticle is fixed, and the other is moved by a constant force as in
      optical-trapping experiments. First, the pulled vesicle stretches into a pear or
      tube shape. Then the inner monolayer in the tube-shaped region is deformed, and a
      cylindrical structure is formed between two vesicles. After stretching the
      cylindrical region, fission occurs near the moved vesicle. Soon after this the
      cylindrical region shrinks. The trapping force approximately 100 pN is needed to
      induce the formation of the cylindrical structure and fission.

PMID- 12059595
TI  - Segmentation of genomic DNA through entropic divergence: power laws and scaling.
AB  - Genomic DNA is fragmented into segments using the Jensen-Shannon divergence. Use
      of this criterion results in the fragments being entropically homogeneous to
      within a predefined level of statistical significance. Application of this
      procedure is made to complete genomes of organisms from archaebacteria,
      eubacteria, and eukaryotes. The distribution of fragment lengths in bacterial and
      primitive eukaryotic DNAs shows two distinct regimes of power-law scaling. The
      characteristic length separating these two regimes appears to be an intrinsic
      property of the sequence rather than a finite-size artifact, and is independent
      of the significance level used in segmenting a given genome. Fragment length
      distributions obtained in the segmentation of the genomes of more highly evolved
      eukaryotes do not have such distinct regimes of power-law behavior.

PMID- 12059594
TI  - Characterization of sleep stages by correlations in the magnitude and sign of
      heartbeat increments.
AB  - We study correlation properties of the magnitude and the sign of the increments
      in the time intervals between successive heartbeats during light sleep, deep
      sleep, and rapid eye movement (REM) sleep using the detrended fluctuation
      analysis method. We find short-range anticorrelations in the sign time series,
      which are strong during deep sleep, weaker during light sleep, and even weaker
      during REM sleep. In contrast, we find long-range positive correlations in the
      magnitude time series, which are strong during REM sleep and weaker during light
      sleep. We observe uncorrelated behavior for the magnitude during deep sleep.
      Since the magnitude series relates to the nonlinear properties of the original
      time series, while the sign series relates to the linear properties, our findings
      suggest that the nonlinear properties of the heartbeat dynamics are more
      pronounced during REM sleep. Thus, the sign and the magnitude series provide
      information which is useful in distinguishing between the sleep stages.

PMID- 12059596
TI  - Dynamic response of adhesion complexes: beyond the single-path picture.
AB  - We analyze the response of molecular adhesion complexes to increasing pulling
      forces (dynamic force spectroscopy) when dissociation can occur along either one
      of two alternative trajectories in the underlying multidimensional energy
      landscape. A great diversity of behaviors (e.g., nonmonotonicity) is found for
      the unbinding force and time as a function of the rate at which the pulling force
      is increased. In particular we identify a class of "harpoon" stickers that bind
      easily but resist strong pulling efficiently. Using existing data, we also
      demonstrate the consequent difficulty of unambiguously determining the features
      of the energy landscape from such single-molecule pulling experiments.

PMID- 12059597
TI  - Dynamics of populations in a changing environment.
AB  - We present an individual-based model of a population that lives in a changing
      environment. The individuals forming the population are subject to mutations and
      selection pressure. Using Monte Carlo simulations we have shown that, depending
      on the values of the mutation rate and selection, the population may reach either
      an active phase (it will survive) or an absorbing phase (it will become extinct).
      We have determined that the transition between the two states (phases) is
      continuous. We have shown that when the selection is weaker the population lives
      in all available space, while if the selection is stronger, it will move to the
      regions where the living conditions are better, avoiding those with more
      difficult conditions. The dependence of the mean time to extinction on the rate
      of mutations has been determined and discussed.

PMID- 12059598
TI  - Molecular gyroscopes and biological effects of weak extremely low-frequency
      magnetic fields.
AB  - Extremely low-frequency magnetic fields are known to affect biological systems.
      In many cases, biological effects display "windows" in biologically effective
      parameters of the magnetic fields: most dramatic is the fact that the relatively
      intense magnetic fields sometimes do not cause appreciable effect, while smaller
      fields of the order of 10-100 microT do. Linear resonant physical processes do
      not explain the frequency windows in this case. Amplitude window phenomena
      suggest a nonlinear physical mechanism. Such a nonlinear mechanism has been
      proposed recently to explain those "windows." It considers the quantum
      interference effects on the protein-bound substrate ions. Magnetic fields cause
      an interference of ion quantum states and change the probability of ion-protein
      dissociation. This ion-interference mechanism predicts specific magnetic-field
      frequency and amplitude windows within which the biological effects occur. It
      agrees with a lot of experiments. However, according to the mechanism, the
      lifetime Gamma(-1) of ion quantum states within a protein cavity should be of
      unrealistic value, more than 0.01 s for frequency band 10-100 Hz. In this paper,
      a biophysical mechanism has been proposed, which (i) retains the attractive
      features of the ion interference mechanism, i.e., predicts physical
      characteristics that might be experimentally examined and (ii) uses the
      principles of gyroscopic motion and removes the necessity to postulate large
      lifetimes. The mechanism considers the dynamics of the density matrix of the
      molecular groups, which are attached to the walls of protein cavities by two
      covalent bonds, i.e., molecular gyroscopes. Numerical computations have shown
      almost free rotations of the molecular gyroscopes. The relaxation time due to van
      der Waals forces was about 0.01 s for the cavity size of 28 A.

PMID- 12059599
TI  - Turing patterns with pentagonal symmetry.
AB  - We explore numerically the formation of Turing patterns in a confined circular
      domain with small aspect ratio. Our results show that stable fivefold patterns
      are formed over a well defined range of disk sizes, offering a possible mechanism
      for inducing the fivefold symmetry observed in early development of regular
      echinoids. Using this pattern as a seed, more complex biological structures can
      be mimicked, such as the pigmentation pattern of sea urchins and the plate
      arrangements of the calyxes of primitive camerate crinoids.

PMID- 12059600
TI  - Stability puzzles in phage lambda.
AB  - In the absence of RecA-mediated cleavage of the repressor, the lambda prophage is
      exceptionally stable. We develop a stochastic model that predicts the stability
      of such epigenetic states from affinities of the molecular components. We find
      that the stability, in particular, depends on the maximum possible cI protein
      production, and on the number of translated cro proteins per transcribed mRNA. We
      apply the model to the behavior of recently published mutants of O(R) and find,
      in particular, that a mutant that overexpress cro behaves in a different way than
      what was predicted, thus suggesting that the current view of the O(R) switch is
      incomplete. The approach described here should be generally applicable to the
      stability of expressed states.

PMID- 12059601
TI  - How spiking neurons give rise to a temporal-feature map: from synaptic plasticity
      to axonal selection.
AB  - A temporal-feature map is a topographic neuronal representation of temporal
      attributes of phenomena or objects that occur in the outside world. We explain
      the evolution of such maps by means of a spike-based Hebbian learning rule in
      conjunction with a presynaptically unspecific contribution in that, if a synapse
      changes, then all other synapses connected to the same axon change by a small
      fraction as well. The learning equation is solved for the case of an array of
      Poisson neurons. We discuss the evolution of a temporal-feature map and the
      synchronization of the single cells' synaptic structures, in dependence upon the
      strength of presynaptic unspecific learning. We also give an upper bound for the
      magnitude of the presynaptic interaction by estimating its impact on the noise
      level of synaptic growth. Finally, we compare the results with those obtained
      from a learning equation for nonlinear neurons and show that synaptic structure
      formation may profit from the nonlinearity.

PMID- 12059602
TI  - Vibrational dynamics of myoglobin determined by the phonon-assisted Mossbauer
      effect.
AB  - The phonon-assisted Mossbauer effect is used to determine the partial phonon
      density of states of the iron within the active center of deoxymyoglobin,
      carboxymyoglobin, and dry and wet metmyoglobin between 40 and 300 K. Between 0
      and 1 meV the iron density of states increases quadratically with the energy, as
      in a Debye solid. Mean sound velocities are extracted from this slope. Between 1
      and 3 meV a nearly quadratic "Debye-like" increase follows due to the similar
      strength of intermolecular and intramolecular forces. Above 3 meV, optical
      vibrations are characteristic for the iron-ligand conformation. The overall mean
      square displacements of the heme iron atom obtained from the density of states
      agree well with the values of Mossbauer absorption experiments below 180 K. In
      the physiological temperature regime the data confirm the existence of harmonic
      vibrations in addition to the protein specific dynamics measured by Mossbauer
      absorption. In the Debye energy regime the mean square displacement of the iron
      is in agreement with that of the hydrogens measured by incoherent neutron
      scattering demonstrating the global character of these modes. At higher energies
      the vibration of the heavy iron atom at 33 meV in metmyoglobin is as large as
      that of the lightweight hydrogens at that energy. A freeze dried, rehydrated
      (h=0.38 g H2O/g protein) metmyoglobin sample shows an excess of states above the
      Debye law between 1 and 3 meV, similar to neutron scattering experiments. The
      room temperature density of states below 3 meV exhibit an increase of the density
      compared to the low temperature data, which can be interpreted as mode softening.

PMID- 12059603
TI  - Comparison of the Maxwell and Boltzmann theory for multilayered dielectric random
      media.
AB  - Based on the transfer matrix theory for electromagnetic fields, we develop a
      corresponding theory for intensity transport in a one-dimensional random medium.
      We show the conditions for which the Maxwell equations, the intensity transport
      theory, and the Boltzmann equation can lead to similar predictions. We generalize
      the transfer matrix theory to study intensity modulated waves and compare its
      predictions with those obtained from the Maxwell and Boltzmann equations.

PMID- 12059604
TI  - Competition effects in the dynamics of tumor cords.
AB  - A general feature of cancer growth is the cellular competition for available
      nutrients. This is also the case for tumor cords, neoplasms forming cylindrical
      structures around blood vessels. Experimental data show that, in their avascular
      phase, cords grow up to a limit radius of about 100 microm, reaching a quasi
      steady-state characterized by a necrotized area separating the tumor from the
      surrounding healthy tissue. Here we use a set of rules to formulate a model that
      describes how the dynamics of cord growth is controlled by the competition of
      tumor cells among themselves and with healthy cells for the acquisition of
      essential nutrients. The model takes into account the mechanical effects
      resulting from the interaction between the multiplying cancer cells and the
      surrounding tissue. We explore the influence of the relevant parameters on the
      tumor growth and on its final state. The model is also applied to investigate
      cord deformation in a region containing multiple nutrient sources and to predict
      the further complex growth of the tumor.

PMID- 12059605
TI  - Spontaneous pattern formation and genetic invasion in locally mating and
      competing populations.
AB  - We present a theoretical model of evolution of spatially distributed populations
      in which organisms mate with and compete against each other only locally. We show
      using both analysis and numerical simulation that the typical dynamics of
      population density variation is a spontaneous formation of isolated groups due to
      competition for resources. The resulting spatial separation between groups
      strongly affects the process of genetic invasion by local reproductive mixing,
      and spatially inhomogeneous genetic distributions are possible in the final
      states. We then consider a specific version of this model in the presence of
      disruptive selection, favoring two fittest types against their genetic
      intermediates. This case can be simplified to a system that involves just two
      nonconserved order parameters: population density and type difference. Since the
      coexistence of two fittest types is unstable in this case, symmetry breaking and
      coarsening occur in type difference, implying eventual dominance by one type over
      another for finite populations. However, such coarsening patterns may be pinned
      by the spontaneously generated spatial separation between isolated groups. The
      long-term evolution of genetic composition is found to be sensitive to the ratio
      of the mating and competition ranges, and other parameters. Our model may provide
      a theoretical basis for consideration of various properties of spatially extended
      evolutionary processes, including spontaneous formation of subpopulations and
      lateral invasion of different types.

PMID- 12059606
TI  - Pattern formation of ion channels with state-dependent charges and diffusion
      constants in fluid membranes.
AB  - A model of mobile, charged ion channels in a fluid membrane is studied. The
      channels may switch between an open and a closed state according to a simple two
      state kinetics with constant rates. The effective electrophoretic charge and the
      diffusion constant of the channels may be different in the closed and in the open
      state. The system is modeled by densities of channel species, obeying simple
      equations of electrodiffusion. The lateral transmembrane voltage profile is
      determined from a cable-type equation. Bifurcations from the homogeneous,
      stationary state appear as hard-mode, soft-mode, or hard-mode oscillatory
      transitions within physiologically reasonable ranges of model parameters. We
      study the dynamics beyond linear stability analysis and derive nonlinear
      evolution equations near the transitions to stationary patterns.

PMID- 12059607
TI  - Neuromuscular control of vocalizations in birdsong: a model.
AB  - We present a dynamical model of the processes involved in birdsong production,
      relating qualitatively its parameters with biological ones. In this way, we
      intend to unify the activity patterns of the muscles controlling the vocal organ
      with the resulting vocalization. With relatively simple paths in the parameter
      space of our model, we reproduce experimental recordings of the Chingolo sparrow
      (Zonotrichia capensis).

PMID- 12059608
TI  - Fast computation with spikes in a recurrent neural network.
AB  - Neural networks with recurrent connections are sometimes regarded as too slow at
      computation to serve as models of the brain. Here we analytically study a
      counterexample, a network consisting of N integrate-and-fire neurons with self
      excitation, all-to-all inhibition, instantaneous synaptic coupling, and constant
      external driving inputs. When the inhibition and/or excitation are large enough,
      the network performs a winner-take-all computation for all possible external
      inputs and initial states of the network. The computation is done very quickly:
      As soon as the winner spikes once, the computation is completed since no other
      neurons will spike. For some initial states, the winner is the first neuron to
      spike, and the computation is done at the first spike of the network. In general,
      there are M potential winners, corresponding to the top M external inputs. When
      the external inputs are close in magnitude, M tends to be larger. If M>1, the
      selection of the actual winner is strongly influenced by the initial states. If a
      special relation between the excitation and inhibition is satisfied, the network
      always selects the neuron with the maximum external input as the winner.

PMID- 12059609
TI  - Model for cardiorespiratory synchronization in humans.
AB  - Recent experimental studies suggest that there is evidence for a synchronization
      between human heartbeat and respiration. We develop a physiologically plausible
      model for this cardiorespiratory synchronization, and numerically show that the
      model can exhibit stable synchronization against given perturbations. In our
      model, in addition to the well-known influence of respiration on heartbeat, the
      influence of heartbeat (and hence blood pressure) on respiration is also
      important for cardiorespiratory synchronization.

PMID- 12059610
TI  - Analytical characterization of spontaneous firing in networks of developing rat
      cultured cortical neurons.
AB  - We have used a multiunit electrode array in extracellular recording to
      investigate changes in the firing patterns in networks of developing rat cortical
      neurons. The spontaneous activity of continual asynchronous firing or the
      alternation of asynchronous spikes and synchronous bursts changed over time so
      that activity in the later stages consisted exclusively of synchronized bursts.
      The spontaneous coordinated activity in bursts produced a variability in
      interburst interval (IBI) sequences that is referred to as "form." The stochastic
      and nonlinear dynamical analysis of IBI sequences revealed that these sequences
      reflected a largely random process and that the form for relatively immature
      neurons was largely oscillatory while the form for the more mature neurons was
      Poisson-like. The observed IBI sequences thus showed changes in form associated
      with both the intrinsic properties of the developing cells and the neural
      response to correlated synaptic inputs due to interaction between the developing
      neural circuits.

PMID- 12059611
TI  - Lattice Boltzmann method for simulating the viscous flow in large distensible
      blood vessels.
AB  - A lattice Boltzmann method for simulating the viscous flow in large distensible
      blood vessels is presented by introducing a boundary condition for elastic and
      moving boundaries. The mass conservation for the boundary condition is tested in
      detail. The viscous flow in elastic vessels is simulated with a pressure-radius
      relationship similar to that of the pulmonary blood vessels. The numerical
      results for steady flow agree with the analytical prediction to very high
      accuracy, and the simulation results for pulsatile flow are comparable with those
      of the aortic flows observed experimentally. The model is expected to find many
      applications for studying blood flows in large distensible arteries, especially
      in those suffering from atherosclerosis, stenosis, aneurysm, etc.

PMID- 12059612
TI  - Oscillations by symmetry breaking in homogeneous networks with electrical
      coupling.
AB  - In many biological systems, the electrical coupling of nonoscillating cells
      generates synchronized membrane potential oscillations. This work describes a
      dynamical mechanism in which the electrical coupling of identical nonoscillating
      cells destabilizes the homogeneous fixed point and leads to network oscillations
      via a Hopf bifurcation. Each cell is described by a passive membrane potential
      and additional internal variables. The dynamics of the internal variables, in
      isolation, is oscillatory, but their interaction with the membrane potential
      damps the oscillations and therefore constructs nonoscillatory cells. The
      electrical coupling reveals the oscillatory nature of the internal variables and
      generates network oscillations. This mechanism is analyzed near the bifurcation
      point, where the spatial structure of the membrane potential oscillations is
      determined by the network architecture and in the limit of strong coupling, where
      the membrane potentials of all cells oscillate in-phase and multiple cluster
      states dominate the dynamics. In particular, we have derived an asymptotic
      behavior for the spatial fluctuations in the limit of strong coupling in fully
      connected networks and in a one-dimensional lattice architecture.

PMID- 12059613
TI  - N-dimensional nonlinear Fokker-Planck equation with time-dependent coefficients.
AB  - An N-dimensional nonlinear Fokker-Planck equation is investigated here by
      considering the time dependence of the coefficients, where drift-controlled and
      source terms are present. We exhibit the exact solution based on the generalized
      Gaussian function related to the Tsallis statistics. Furthermore, we show that a
      rich class of diffusive processes, including normal and anomalous ones, can be
      obtained by changing the time dependence of the coefficients.

PMID- 12059614
TI  - Anomalous tag diffusion in the asymmetric exclusion model with particles of
      arbitrary sizes.
AB  - Anomalous behavior of correlation functions of tagged particles are studied in
      generalizations of the one-dimensional asymmetric exclusion problem. In these
      generalized models the range of the hard-core interactions are changed and the
      restriction of relative ordering of the particles is partially broken. The models
      probing these effects are those of biased diffusion of particles having size
      S=0,1,2, em leader, or an effective negative "size" S=-1,-2, em leader, in units
      of lattice space. Our numerical simulations show that irrespective of the range
      of the hard-core potential, as long some relative ordering of particles are kept,
      we find suitable sliding-tag correlation functions whose fluctuations growth with
      time anomalously slow (t1/3), when compared with the normal diffusive behavior
      (t1/2). These results indicate that the critical behavior of these stochastic
      models are in the Kardar-Parisi-Zhang (KPZ) universality class. Moreover a
      previous Bethe-ansatz calculation of the dynamical critical exponent z, for size
      S> or =0 particles is extended to the case S<0 and the KPZ result z=3/2 is
      predicted for all values of S in Z.

PMID- 12059615
TI  - Separation mechanisms underlying vector chromatography in microlithographic
      arrays.
AB  - Micropatterned chips possessing an asymmetric, spatially periodic array of
      obstacles enable the vector (directional) chromatographic separation of charged
      particles animated by an external electric field. We apply a network theory to
      analyze the chip-scale (L-scale) transport of finite-size Brownian particles in
      such devices and identify those factors that break the symmetry of the chip-scale
      particle mobility tensor, most importantly the hydrodynamic wall effects between
      the particles and the obstacle surfaces. Our analysis contrasts with prevailing
      separation theories, which are limited to effectively point-size particles, for
      which wall effects are negligible. These theories require a biasing of obstacle
      scale (l-scale; l<<L) bifurcation branches within the network. Such bifurcations
      are shown to constitute but one factor in modeling the vector chromatography of
      finite-size particles, and not necessarily the dominant factor.

PMID- 12059616
TI  - Interface dynamics and kinetic roughening in fractals.
AB  - We consider the dynamics and kinetic roughening of single-valued interfaces in
      two-dimensional fractal media. Assuming that the local height difference
      distribution function of the fronts obeys Levy statistics with a well-defined
      power-law decay exponent, we derive analytic expressions for the local scaling
      exponents. We also show that the kinetic roughening of the interfaces displays
      anomalous scaling and multiscaling in the relevant correlation functions. For
      invasion percolation models, the exponents can be obtained from the fractal
      geometry of percolation clusters. Our predictions are in excellent agreement with
      numerical simulations.

PMID- 12059617
TI  - Directed random walks in continuous space.
AB  - The investigation on diffusion with directed motion in a two-dimensional
      continuous space is completed by using the model of the continuous directed
      random walks. The average square end-to-end distance <R2(t)> approximately t(2nu)
      is calculated. The results show that this type of walks belongs asymptotically to
      the same class (nu=1.0) as the ballistic motions. For short time, we observe a
      crossover from purely random walks (nu=0.5) to ballistic motions (nu=1.0). The
      dependence of the crossover on the direction parameter theta is studied. There
      exists a scaling relation of the form <R2(t)> approximately tf(t/theta(-2)). The
      return probability P00(t) is also investigated and the scaling form similar to
      <R2(t)> is obtained.

PMID- 12059618
TI  - Scaling laws for the equation of state of flexible and linear tangent hard sphere
      chains.
AB  - The influence that molecular flexibility has on the phase diagram and equation of
      state of hard sphere chains is examined. In the isotropic phase the equation of
      state is insensitive to flexibility; rigid chains display the same equation of
      state as flexible chains. However, with the onset of liquid crystalline phases
      for rigid molecules this similarity disappears. Differences are also apparent
      between the rigid and flexible models in the solid phase. Wertheim's
      thermodynamic perturbation theory has been extended to describe the solid phase
      of fully flexible chains and excellent agreement with simulation results is seen.
      A scaling is proposed that, when applied to the fully flexible model, reproduces
      simulation results for a linear rigid model. It is shown that for the fully
      flexible model the compressibility factor for the fluid and solid phases scale
      with the number of monomers m. The compressibility factor for the linear model
      scales with m in the isotropic fluid, and becomes independent of m in the
      nematic, smectic, and solid phases.

PMID- 12059619
TI  - Flow alignment in a shearing nematic liquid crystal near a charged surface.
AB  - The flow alignment angle theta(eff)(y) and effective rotational viscosity
      coefficient gamma(eff)1 are investigated for polar liquid crystals (LCs), such as
      4-n-octyloxy-4'-cyanobiphenyl (8OCB), in the vicinity of a charged bounding
      surface. gamma(eff)1 and theta(eff)(y) are calculated, for the stationary regime,
      in the framework of the conventional Ericksen-Leslie theory. Calculations of
      gamma(eff)1, for the homeotropic alignment of 8OCB molecules, at a charged indium
      tin oxide-coated glass plate show an increase in gamma(eff)1 up to 7.8%.

PMID- 12059620
TI  - Formation mechanism and dynamics in polymer surface gratings.
AB  - We present the results of time-dependent x-ray and visible light (VIS) scattering
      measurements during formation of surface relief grating (SRG). These gratings are
      formed on polymer films containing azobenzene side groups during pulselike
      exposure with a holographic pattern of circularly polarized light at 488 nm. The
      SRG formation is accompanied by a density grating just below the film surface.
      Assuming viscoelastic flow, a change in polymer's elastic properties upon light
      exposure can explain the massive material transport. Finite element calculations
      reveal a dynamic model of grating formation characterized by different relaxation
      times. The simultaneous formation of a surface relief grating and of a density
      grating explains quantitatively the findings of the VIS experiment, but only
      qualitatively the findings of the x-ray measurements.

PMID- 12059621
TI  - Tension and solute depletion in multilamellar vesicles.
AB  - We show that a metastable multilamellar vesicle ("onion"), in contact with excess
      solvent, can spontaneously deplete solute molecules from its interior through an
      unusual, entropy-driven mechanism. Fluctuation entropy is gained as the uneven
      partition of solute molecules helps the onion relieve tension in its lamellae.
      This mechanism accounts for recent experiments on the interaction between
      uncharged phospholipid onions and dissolved sugars.

PMID- 12059622
TI  - Simple model for the kinetics of packaging of DNA into a capsid against an
      external force.
AB  - We propose a simple model for the kinetics of packaging of viral DNA into a
      capsid against an external force trying to prevent it. The model leads to a
      Butler-Volmer-type dependence of the rate of packaging on the pulling force F.

PMID- 12059623
TI  - Comment on "Portevin-Le Chatelier effect".
AB  - Instabilities of plastic flow in alloys and the associated deformation patterns
      are currently attracting a lot of attention. We comment on a recent investigation
      by Franklin et al. [Phys. Rev. E 62, 8195 (2000)] on one such type of
      instability, the Portevin-Le Chatelier effect, attempting to clarify a few points
      about the instability mechanism as well as the reported experimental results.

PMID- 12059625
TI  - Drifting pattern domains in a reaction-diffusion system with nonlocal coupling.
AB  - Drifting pattern domains (DPDs), i.e., moving localized patches of traveling
      waves embedded in a stationary (Turing) pattern background and vice versa, are
      observed in simulations of a reaction-diffusion model with nonlocal coupling.
      Within this model, a region of bistability between Turing patterns and traveling
      waves arises from a codimension-2 Turing-wave bifurcation (TWB). DPDs are found
      within that region in a substantial distance from the TWB. We investigated the
      dynamics of single interfaces between Turing and wave patterns. It is found that
      DPDs exist due to a locking of the interface velocities, which is imposed by the
      absence of space-time defects near these interfaces.

PMID- 12059627
TI  - Halting viruses in scale-free networks.
AB  - The vanishing epidemic threshold for viruses spreading on scale-free networks
      indicate that traditional methods, aiming to decrease a virus' spreading rate
      cannot succeed in eradicating an epidemic. We demonstrate that policies that
      discriminate between the nodes, curing mostly the highly connected nodes, can
      restore a finite epidemic threshold and potentially eradicate a virus. We find
      that the more biased a policy is towards the hubs, the more chance it has to
      bring the epidemic threshold above the virus' spreading rate. Furthermore, such
      biased policies are more cost effective, requiring less cures to eradicate the
      virus.

PMID- 12059626
TI  - Discrete four-stroke quantum heat engine exploring the origin of friction.
AB  - The optimal power performance of a first-principle quantum heat engine model
      shows friction-like phenomena when the internal fluid Hamiltonian does not
      commute with the external control field. The model is based on interacting two
      level systems where the external magnetic field serves as a control variable.

PMID- 12059628
TI  - Information transfer in chaos-based communication.
AB  - This paper presents fundamentals of a theory to characterize chaos-based
      communication. We describe the amount of information a dynamical system is able
      to transmit, the dynamical channel capacity, which takes into account the
      information that a dynamical system generates.

PMID- 12059629
TI  - Spatial periodic synchronization of chaos in coupled ring and linear arrays of
      chaotic systems.
AB  - Dynamic behaviors of coupled ring and linear arrays of unidirectionally coupled
      Lorenz oscillators are studied numerically. It is found that the chaotic rotating
      waves generated from the ring propagate with spatial periodic synchronization
      along the linear array, that is to say, two chaotic oscillators in the linear
      array are synchronized if the number of oscillators (spatial distance) between
      them is a multiple of oscillator number in the ring. Numerically it is shown that
      the stabilities of the synchronized states are enhanced by chaos, and degraded
      when the oscillators are far from the ring.

PMID- 12059630
TI  - Suppression and enhancement of diffusion in disordered dynamical systems.
AB  - The impact of quenched disorder on deterministic diffusion in chaotic dynamical
      systems is studied. As a simple example, we consider piecewise linear maps on the
      line. In computer simulations we find a complex scenario of multiple suppression
      and enhancement of normal diffusion, under variation of the perturbation
      strength. These results are explained by a theoretical approximation, showing
      that the oscillations emerge as a direct consequence of the unperturbed diffusion
      coefficient, which is known to be a fractal function of a control parameter.

PMID- 12059631
TI  - Pattern formation of spiral waves in an inhomogeneous medium with small-world
      connections.
AB  - Pattern formation of spiral waves in an inhomogeneous excitable medium with small
      world connections is investigated. In both cases, with completely local regular
      connections and with completely random connections, spiral waves cannot survive
      in the given inhomogeneous medium. It is found that with small-world connections
      (basically local connections plus a small number of random connections) a well
      behaved spiral wave can be formed against the destructive role of the
      inhomogeneous medium. There also exists an optimal fraction of random connections
      which can greatly enhance the probability of spiral wave formation; this
      resembles the behavior of stochastic resonance.

PMID- 12059632
TI  - Fractal analysis of chaotic classical scattering in a cut-circle billiard with
      two openings.
AB  - We investigate the fractal behavior of the transmission of a classical particle
      through a circular billiard with a straight cut and two openings. As the size of
      the cut varies, the phase space of the closed billiard shows a full range of
      dynamical behavior, including integrable behavior, soft chaos (mixed phase
      space), and hard chaos (ergodic and mixing). For an open billiard, we numerically
      find the exit opening as a function of the incident angle. When the billiard is
      chaotic, the result shows self-similarity and infinite complexity. We calculate
      the fractal dimension of this structure using a box-counting method when two
      parameters, the size of the cut and the size of the openings, are varied.

PMID- 12059633
TI  - Sensitivity to perturbations in a quantum chaotic billiard.
AB  - The Loschmidt echo (LE) measures the ability of a system to return to the initial
      state after a forward quantum evolution followed by a backward perturbed one. It
      has been conjectured that the echo of a classically chaotic system decays
      exponentially, with a decay rate given by the minimum between the width Gamma of
      the local density of states and the Lyapunov exponent. As the perturbation
      strength is increased one obtains a crossover between both regimes. These
      predictions are based on situations where the Fermi golden rule (FGR) is valid.
      By considering a paradigmatic fully chaotic system, the Bunimovich stadium
      billiard, with a perturbation in a regime for which the FGR manifestly does not
      work, we find a crossover from Gamma to Lyapunov decay. We find that, challenging
      the analytic interpretation, these conjectures are valid even beyond the expected
      range.

PMID- 12059634
TI  - Absence of determinism in El Nino Southern Oscillation.
AB  - We perform two direct determinism tests on the El Nino Southern Oscillation index
      monthly average series. The results indicate that, for timescales over 1 month,
      the series does not exhibit determinism, an essential feature of chaos.

PMID- 12059635
TI  - Collective phase locked states in a chain of coupled chaotic oscillators.
AB  - We discuss the emergence of a collective phase locked state in an open chain of N
      unidirectionally weakly coupled nonidentical chaotic oscillators. Such a regime
      is characterized by a Lyapunov spectrum where N-1 exponents that were zero in the
      uncoupled regime assume negative values as the coupling strength increases. The
      dynamics of such collective state is studied, and a comparison is drawn with the
      case of phase synchronization of a pair of coupled chaotic oscillators. In
      particular, it is shown that a full phase synchronized state cannot be
      constructed without at least partial correlation in the chaotic amplitudes.

PMID- 12059636
TI  - Signatures of prelocalized states in classically chaotic systems.
AB  - We investigate the statistics of eigenfunction intensities P(/psi/(2)) in
      dynamical systems with classical chaotic diffusion. Our results contradict some
      recent theoretical considerations that challenge the applicability of field
      theoretical predictions, derived in a different framework for diffusive
      disordered samples. For two-dimensional systems, the tails of P(/psi/(2))
      contradict the results of the optimal fluctuation method, but agree very well
      with the predictions of the nonlinear sigma model.

PMID- 12059637
TI  - Self-similar solutions for conic cusps formation at the surface of dielectric
      liquids in electric field.
AB  - The nonlinear dynamics is studied for the free surface of an ideal dielectric
      fluid in an electric field. Self-similar solutions of electrohydrodynamic
      equations describing the formation of surface conic cusps are revealed. The
      behavior of physical quantities (field strength, fluid velocity, and surface
      curvature) near the singularity is established. The threshold value of the fluid
      dielectric constant required for the proposed mechanism of a cusp development is
      found.

PMID- 12059638
TI  - Quiet direct simulation of Eulerian fluids.
AB  - The direct simulation Monte Carlo method of modeling fluids requires sampling one
      or more random variables every time step for each particle. In this paper a
      "quiet Monte Carlo" technique is proposed that eliminates the random sampling and
      the noise it produces by deterministically generating a small number of
      computational particles. The technique is applied to particle equations of motion
      appropriate for modeling an Eulerian fluid. Results indicate that strong one- and
      two-dimensional shocks with large dynamic ranges are accurately represented with
      only a few particles per cell.

PMID- 12059639
TI  - Linear superposition principle for partially coherent solitons.
AB  - The existence of a linear superposition principle is demonstrated for partially
      coherent solitons with identical intensity profiles that are supported by the
      same medium. Since such degenerate partially coherent solitons are generic for
      saturable as well as for Kerr-like nonlinear media, our results are relevant to
      any non-instantaneous nonlinear media. The proposed superposition principle
      suggests a physical interpretation of partially coherent solitons as generalized
      linear modes of their self-induced waveguides. The power of such a superposition
      principle is illustrated by identifying soliton structures with controllable
      coherence properties both in logarithmically saturable and in Kerr-like nonlinear
      media.

PMID- 12059640
TI  - Numerical method for complex moving boundary problems in a Cartesian fixed grid.
AB  - We propose a numerical method to capture and track complex moving boundaries
      advected in flows. Our method is based on the level set method, but it overcomes
      the problem of accumulation of reinitialization error in the level set method.

PMID- 12059641
TI  - Geometric fractal growth model for scale-free networks.
AB  - We introduce a deterministic model for scale-free networks, whose degree
      distribution follows a power law with the exponent gamma. At each time step, each
      vertex generates its offspring, whose number is proportional to the degree of
      that vertex with proportionality constant m-1 (m>1). We consider the two cases:
      First, each offspring is connected to its parent vertex only, forming a tree
      structure. Second, it is connected to both its parent and grandparent vertices,
      forming a loop structure. We find that both models exhibit power-law behaviors in
      their degree distributions with the exponent gamma = 1+ln(2m-1)/ln m. Thus, by
      tuning m, the degree exponent can be adjusted in the range, 2 < gamma < 3. We
      also solve analytically a mean shortest-path distance d between two vertices for
      the tree structure, showing the small-world behavior, that is, d approximately ln
      N/ln K macro, where N is system size, and k macro is the mean degree. Finally, we
      consider the case that the number of offspring is the same for all vertices, and
      find that the degree distribution exhibits an exponential-decay behavior.

PMID- 12059642
TI  - Sampling rare events: statistics of local sequence alignments.
AB  - A method to calculate probability distributions in regions where the events are
      very unlikely (e.g., p approximately 10(-40)) is presented. The basic idea is to
      map the underlying model on a physical system. The system is simulated at a low
      temperature, such that preferably configurations with originally low
      probabilities are generated. Since the distribution of such a physical system is
      known, the original unbiased distribution can be obtained. As an application,
      local alignment of protein sequences is studied. The deviation of the
      distribution p(S) of optimum scores from the extreme-value distribution is
      quantified. This deviation decreases with growing sequence length.

PMID- 12059643
TI  - Behavior of damage spreading in the two-dimensional Blume-Capel model.
AB  - The damage spreading technique has been used to study the general integer and
      half-integer spin-S Blume-Capel model on the square lattice within a Metropolis
      type dynamics. For S=1 and 2 integer spins, our results suggest that there exists
      one multicritical point along the order-disorder transition line; for S=3/2 and
      5/2 half-integer spins, our results show that this multicritical behavior does
      not exist for this model.

PMID- 12059644
TI  - Finite-size investigation of scaling corrections in the square-lattice three
      state Potts antiferromagnet.
AB  - We investigate the finite-temperature corrections to scaling in the three-state
      square-lattice Potts antiferromagnet, close to the critical point at T=0.
      Numerical diagonalization of the transfer matrix on semi-infinite strips of width
      L sites, 4 < or = L < or = 14, yields finite-size estimates of the corresponding
      scaled gaps, which are extrapolated to L --> infinity. Owing to the
      characteristics of the quantities under study, we argue that the natural variable
      to consider is x identical with L e(-2 beta). For the extrapolated scaled gaps we
      show that square-root corrections, in the variable x, are present, and provide
      estimates for the numerical values of the amplitudes of the first- and second
      order correction terms, for both the first and second scaled gaps. We also
      calculate the third scaled gap of the transfer matrix spectrum at T=0, and find
      an extrapolated value of the decay-of-correlations exponent, eta(3)=2.00(1). This
      is at odds with earlier predictions, to the effect that the third relevant
      operator in the problem would give eta(P(stagg))=3, corresponding to the
      staggered polarization.

PMID- 12059645
TI  - Transition regimes for growing crack populations.
AB  - Numerous observational papers on crack populations in the material and geological
      sciences suggest that cracks evolve in such a way as to organize in specific
      patterns. However, very little is known about how and why the self-organization
      comes about. We use a model of tensile-like cracks with friction in order to
      study the time and space evolution of normal faults. The premise of this spring
      block analog is that one could model crustal deformation for long time scales
      assuming a brittle layer coupled to a ductile substrate. The long time-scale
      physics incorporated into the model are slip-weakening friction, strain-hardening
      rheology for coupling the two layers, and randomly distributed yield strength of
      the brittle layer. We investigate how the evolution of populations of cracks
      depends on these three effects, using linear stability analysis to calculate the
      stable regimes for the friction as well as numerical simulations to model the
      nonlinear interactions of the cracks. We find that we can scale the problem to
      reduce the relevant parameters to a single one, the slip weakening. We show that
      the distribution of lengths of active cracks makes a transition from an
      exponential at very low strains, where crack nucleation prevails, to a power law
      at low to intermediate strains, where crack growth prevails, to an exponential
      distribution of the largest cracks at higher strains, where coalescence
      dominates. There is evidence of these different length distributions in
      continental and oceanic normal faults. For continental deformation the strain is
      low, and the faults have power-law frequency-size distributions. For mid-ocean
      ridge flanks the strain is greater, up to an order of magnitude higher than the
      continental strain, and faults have exponential-like frequency-size
      distributions. No theory has been offered to explain this difference in the
      distributions of continental and mid-ocean faults. In this paper we argue that
      they are indicative of different stages of evolution. The former faults are at an
      early stage of relatively small deformation, while the latter are at a later
      stage of the evolution. For high strain the faults reach a saturation regime with
      system size cracks evenly spaced in proportion to the brittle layer thickness. We
      asymptotically approximate the time space evolution of faults as a long time
      scale phenomenon, thereby avoiding modeling the short time-scale earthquakes. We
      show that this assumption is valid, which implies that the faults that creep and
      faults with earthquakes display the same time and space evolutions.

PMID- 12059646
TI  - Evolution model with a cumulative feedback coupling.
AB  - The paper is concerned with a toy model that generalizes the standard Lotka
      Volterra equation for a certain population by introducing a competition between
      instantaneous and accumulative, history-dependent nonlinear feedback the origin
      of which could be a contribution from any kind of mismanagement in the past. The
      results depend on the sign of that additional cumulative loss or gain term of
      strength lambda. In case of a positive coupling the system offers a maximum gain
      achieved after a finite time but the population will die out in the long time
      limit. In this case the instantaneous loss term of strength u is irrelevant and
      the model exhibits an exact solution. In the opposite case lambda<0 the time
      evolution of the system is terminated in a crash after t(s) provided u=0. This
      singularity after a finite time can be avoided if u not equal to 0. The approach
      may well be of relevance for the qualitative understanding of more realistic
      descriptions.

PMID- 12059647
TI  - Aging effects in the quantum dynamics of a dissipative free particle: non-Ohmic
      case.
AB  - We report the results related to the two-time dynamics of the coordinate of a
      quantum free particle, damped through its interaction with a fractal thermal bath
      (non-Ohmic coupling approximately omega(delta) with 0<delta <1 or 1<delta <2).
      When the particle is localized, its position does not age. When it undergoes
      anomalous diffusion, only its displacement may be defined. It is shown to be an
      aging variable. The finite temperature aging regime is self-similar. It is
      described by a scaling function of the ratio t(w)/tau of the waiting time to the
      observation time, as characterized by an exponent directly linked to delta.

PMID- 12059648
TI  - Packing-limited growth.
AB  - We consider growing spheres seeded by random injection in time and space. Growth
      stops when two spheres meet leading eventually to a jammed state. We study the
      statistics of growth limited by packing theoretically in d dimensions and via
      simulation in d=2, 3, and 4. We show how a broad class of such models exhibit
      distributions of sphere radii with a universal exponent. We construct a scaling
      theory that relates the fractal structure of these models to the decay of their
      pore space, a theory that we confirm via numerical simulations. The scaling
      theory also predicts an upper bound for the universal exponent and is in exact
      agreement with numerical results for d=4.

PMID- 12059649
TI  - Attack vulnerability of complex networks.
AB  - We study the response of complex networks subject to attacks on vertices and
      edges. Several existing complex network models as well as real-world networks of
      scientific collaborations and Internet traffic are numerically investigated, and
      the network performance is quantitatively measured by the average inverse
      geodesic length and the size of the largest connected subgraph. For each case of
      attacks on vertices and edges, four different attacking strategies are used:
      removals by the descending order of the degree and the betweenness centrality,
      calculated for either the initial network or the current network during the
      removal procedure. It is found that the removals by the recalculated degrees and
      betweenness centralities are often more harmful than the attack strategies based
      on the initial network, suggesting that the network structure changes as
      important vertices or edges are removed. Furthermore, the correlation between the
      betweenness centrality and the degree in complex networks is studied.

PMID- 12059650
TI  - Reversible stretching of random heteropolymers.
AB  - We analyze the equilibrium response of random heteropolymers to mechanical
      deformation. In contrast to homopolymer response, the stress-induced
      transformation of a heteropolymer from globule to coil need not be sharp. For
      chain lengths relevant to biological macromolecules, intermediate necklace-like
      structures dominate over a range of applied force. Stability of these
      conformations is primarily a consequence of solvation: In a typical necklace,
      relatively solvophilic regions of the chain are extended, while solvophobic
      regions remain compact. In the long-chain limit, homopolymeric behavior is
      recovered. Our results suggest that only select polypeptide sequences should
      unfold reproducibly at a specific force, explaining recent experimental
      observations.

PMID- 12059651
TI  - Temperature-entropy formulation of thermoelectric thermodynamic cycles.
AB  - A temperature-entropy formulation is derived for thermoelectric devices.
      Thermoelectric chiller and generator cycles can then be cast in the same
      irreversible thermodynamics framework commonly applied to conventional large
      scale cooling and power generation equipment, including a transparent
      identification of the principal energy flows and performance bottlenecks
      (dissipation). Distinct differences in chiller versus generator mode are
      highlighted and illustrated with data from commercial thermoelectric units.

PMID- 12059652
TI  - Improved semiclassical density matrix: taming caustics.
AB  - We present a simple method to deal with caustics in the semiclassical
      approximation to the thermal density matrix of a particle moving on the line. For
      simplicity, only its diagonal elements are considered. The only ingredient we
      require is the knowledge of the extrema of the Euclidean action. The procedure
      makes use of complex trajectories, and is applied to the quartic double-well
      potential.

PMID- 12059654
TI  - Phase transitions in nonequilibrium d-dimensional models with q absorbing states.
AB  - A nonequilibrium Potts-like model with q absorbing states is studied using Monte
      Carlo simulations. In two dimensions and q=3 the model exhibits a discontinuous
      transition. For the three-dimensional case and q=2 the model exhibits a
      continuous transition with beta=1 (mean field). Simulations are inconclusive,
      however, in the two-dimensional case for q=2. We suggest that in this case the
      model is close to or at the crossing point of lines separating three different
      types of phase transitions. The proposed phase diagram in the (q,d) plane is very
      similar to that of the equilibrium Potts model. In addition, our simulations
      confirm the field-theory prediction that in two dimensions a branching
      annihilating random walk model without parity conservation belongs to the
      directed percolation universality class.

PMID- 12059653
TI  - Phase transition of a two-dimensional binary spreading model.
AB  - We investigated the phase transition behavior of a binary spreading process in
      two dimensions for different particle diffusion strengths (D). We found that N>2
      cluster mean-field approximations must be considered to get consistent singular
      behavior. The N=3,4 approximations result in a continuous phase transition
      belonging to a single universality class along the D subset (0,1) phase
      transition line. Large scale simulations of the particle density confirmed mean
      field scaling behavior with logarithmic corrections. This is interpreted as
      numerical evidence supporting the bosonic field theoretical prediction that the
      upper critical dimension in this model is d(c)=2. The pair density scales in a
      similar way but with an additional logarithmic factor to the order parameter. At
      the D=0 end point of the transition line we found directed percolation
      criticality.

PMID- 12059655
TI  - Glassy random matrix models.
AB  - This paper discusses random matrix models that exhibit the unusual phenomena of
      having multiple solutions at the same point in phase space. These matrix models
      have gaps in their spectrum or density of eigenvalues. The free energy and
      certain correlation functions of these models show differences for the different
      solutions. This study presents evidence for the presence of multiple solutions
      both analytically and numerically. As an example this paper discusses the double
      well matrix model with potential V(M)=-(mu/2)M(2)+(g/4)M(4), where M is a random
      N x N matrix (the M(4) matrix model) as well as the Gaussian Penner model with
      V(M)=(mu/2)M(2)-t ln M. First this paper studies what these multiple solutions
      are in the large N limit using the recurrence coefficient of the orthogonal
      polynomials. Second it discusses these solutions at the nonperturbative level to
      bring out some differences between the multiple solutions. Also presented are the
      two-point density-density correlation functions, which further characterize these
      models in a different universality class. A motivation for this work is that
      variants of these models have been conjectured to be models of certain structural
      glasses in the high temperature phase.

PMID- 12059656
TI  - Kinematic reduction of reaction-diffusion fronts with multiplicative noise:
      derivation of stochastic sharp-interface equations.
AB  - We study the dynamics of generic reaction-diffusion fronts, including pulses and
      chemical waves, in the presence of multiplicative noise. We discuss the
      connection between the reaction-diffusion Langevin-like field equations and the
      kinematic (eikonal) description in terms of a stochastic moving-boundary or sharp
      interface approximation. We find that the effective noise is additive and we
      relate its strength to the noise parameters in the original field equations, to
      first order in noise strength, but including a partial resummation to all orders
      which captures the singular dependence on the microscopic cutoff associated with
      the spatial correlation of the noise. This dependence is essential for a
      quantitative and qualitative understanding of fluctuating fronts, affecting both
      scaling properties and nonuniversal quantities. Our results predict phenomena
      such as the shift of the transition point between the pushed and pulled regimes
      of front propagation, in terms of the noise parameters, and the corresponding
      transition to a non-Kardar-Parisi-Zhang universality class. We assess the
      quantitative validity of the results in several examples including equilibrium
      fluctuations and kinetic roughening. We also predict and observe a noise-induced
      pushed-pulled transition. The analytical predictions are successfully tested
      against rigorous results and show excellent agreement with numerical simulations
      of reaction-diffusion field equations with multiplicative noise.

PMID- 12059657
TI  - Precursory dynamics in threshold systems.
AB  - A precursory dynamics, motivated by the analysis of recent experiments on solid
      on-solid friction, is introduced in a continuous cellular automaton that mimics
      the physics of earthquake source processes. The resulting system of equations for
      the interevent cycle can be decoupled and yields an analytical solution in the
      mean-field limit, exhibiting a smoothing effect of the dynamics on the stress
      field. Simulation results show the resulting departure from scaling at the large
      event end of the frequency distribution, and support claims that the field
      leakage may parametrize the superposition of scaling and characteristic regimes
      observed in real earthquake faults.

PMID- 12059658
TI  - Stochastic instability of quasi-isolated systems.
AB  - The stability of solutions to evolution equations with respect to small
      stochastic perturbations is considered. The stability of a stochastic dynamical
      system is characterized by the local stability index. The limit of this index
      with respect to infinite time describes the asymptotic stability of a stochastic
      dynamical system. Another limit of the stability index is given by the vanishing
      intensity of stochastic perturbations. A dynamical system is stochastically
      unstable when these two limits do not commute with each other. Several examples
      illustrate the thesis that there always exist such stochastic perturbations that
      render a given dynamical system stochastically unstable. The stochastic
      instability of quasi-isolated systems is responsible for the irreversibility of
      time arrow.

PMID- 12059659
TI  - Corporate default behavior: a simple stochastic model.
AB  - We compare observed temporal dynamics of corporate default to a first-passage
      time model and find that corporations default as if via diffusive dynamics.

PMID- 12059660
TI  - Density matrix negativity for two oscillators in an Agarwal bath.
AB  - A system of two harmonic oscillators is placed in an Agarwal bath. The resulting
      quantum master equations are studied with the help of quantum characteristic
      functions. The density matrix positivity is investigated in view of the recent
      interest in searching for a sound quantum dissipation theory. An analytical
      criterion is derived for density matrix negativity for two uncoupled oscillators.
      It is found that, for an initial two-oscillator squeezed state with a real
      squeezing parameter s, density matrix negativity occurs for two uncoupled
      oscillators at temperatures lower than Planck's over 2 pi omega/(k(B) ln coth/s/)
      with omega the oscillator frequency and k(B) the Boltzmann factor. As a by
      product an analytical expression is also obtained for determining the quantum
      separability of two uncoupled oscillators. The effects of interoscillator
      coupling on density matrix negativity are discussed.

PMID- 12059661
TI  - Influence of expansion on hierarchical structure.
AB  - We study a one-dimensional model of gravitational instability in an Einstein-de
      Sitter universe. Scaling in both space and time results in an autonomous set of
      coupled Poisson-Vlasov equations for both the field and phase space density, and
      the N-body problem. Using dynamical simulation, we find direct evidence of
      hierarchical clustering. A multifractal analysis reveals a bifractal geometry
      similar to that observed in the distribution of galaxies. To demonstrate the role
      of scaling, we compare the system to other one-dimensional models recently
      employed to study structure formation. Finally we show that the model yields an
      estimate of the time of galaxy formation of the correct order.

PMID- 12059662
TI  - Quantum field theory of forward rates with stochastic volatility.
AB  - In a recent formulation of a quantum field theory of forward rates, the
      volatility of the forward rates was taken to be deterministic. The field theory
      of the forward rates is generalized to the case of stochastic volatility. Two
      cases are analyzed, first when volatility is taken to be a function of the
      forward rates, and second when volatility is taken to be an independent quantum
      field. Since volatility is a positive valued quantum field, the full theory turns
      out to be an interacting nonlinear quantum field theory in two dimensions. The
      state space and Hamiltonian for the interacting theory are obtained, and shown to
      have a nontrivial structure due to the manifold moving with a constant velocity.
      The no arbitrage condition is reformulated in terms of the Hamiltonian of the
      system, and then exactly solved for the nonlinear interacting case.

PMID- 12059663
TI  - Phase transitions in self-gravitating systems: self-gravitating fermions and hard
      sphere models.
AB  - We discuss the nature of phase transitions in self-gravitating systems both in
      the microcanonical and in the canonical ensemble. We avoid the divergence of the
      gravitational potential at short distances by considering the case of self
      gravitating fermions and hard-sphere models. Depending on the values of the
      parameters, three kinds of phase transitions (of zero, first, and second order)
      are evidenced. They separate a "gaseous" phase with a smoothly varying
      distribution of matter from a "condensed" phase with a core-halo structure. We
      propose a simple analytical model to describe these phase transitions. We
      determine the value of energy (in the microcanonical ensemble) and temperature
      (in the canonical ensemble) at the transition point and we study their dependence
      on the degeneracy parameter (for fermions) or on the size of the particles (for a
      hard-sphere gas). Scaling laws are obtained analytically in the asymptotic limit
      of a small short distance cutoff. Our analytical model captures the essential
      physics of the problem and compares remarkably well with the full numerical
      solutions. We also stress some analogies with the liquid-gas transition and with
      the Blume-Emery-Griffiths model with infinite range interactions. In particular,
      our system presents two tricritical points at which the transition passes from
      first order to second order.

PMID- 12059665
TI  - Disordered backgammon model.
AB  - In this paper we consider an exactly solvable model that displays glassy behavior
      at zero temperature due to entropic barriers. The new ingredient of the model is
      the existence of different energy scales or modes associated with different
      relaxational time scales. Low-temperature relaxation takes place by partial
      equilibration of successive lower-energy modes. An adiabatic scaling solution,
      defined in terms of a threshold energy scale epsilon*, is proposed. For such a
      solution, modes with energy epsilon>>epsilon* are equilibrated at the bath
      temperature, modes with epsilon<<epsilon* remain out of equilibrium, and
      relaxation occurs in the neighborhood of the threshold epsilon approximately
      epsilon*. The model is presented as a toy example to investigate the conditions
      related to the existence of an effective temperature in glassy systems and its
      possible dependence on the energy sector is probed by the corresponding
      observable.

PMID- 12059664
TI  - Adsorption and collapse transitions in a linear polymer chain near an attractive
      wall.
AB  - We deduce the qualitative phase diagram of a long flexible neutral polymer chain
      immersed in a poor solvent near an attracting surface using phenomenological
      arguments. The actual positions of the phase boundaries are estimated numerically
      from series expansion up to 19 sites of a self-attracting self-avoiding walk in
      three dimensions. In two dimensions, we calculate phase boundaries analytically
      in some cases for a partially directed model. Both the numerical and analytical
      results corroborate the proposed qualitative phase diagram.

PMID- 12059666
TI  - Beyond blobs in percolation cluster structure: the distribution of 3-blocks at
      the percolation threshold.
AB  - The incipient infinite cluster appearing at the bond percolation threshold can be
      decomposed into singly connected "links" and multiply connected "blobs." Here we
      decompose blobs into objects known in graph theory as 3-blocks. A 3-block is a
      graph that cannot be separated into disconnected subgraphs by cutting the graph
      at two or fewer vertices. Clusters, blobs, and 3-blocks are special cases of k
      blocks with k=1, 2, and 3, respectively. We study bond percolation clusters at
      the percolation threshold on two-dimensional (2D) square lattices and three
      dimensional cubic lattices and, using Monte Carlo simulations, determine the
      distribution of the sizes of the 3-blocks into which the blobs are decomposed. We
      find that the 3-blocks have fractal dimension d(3)=1.2+/-0.1 in 2D and 1.15+/-0.1
      in 3D. These fractal dimensions are significantly smaller than the fractal
      dimensions of the blobs, making possible more efficient calculation of
      percolation properties. Additionally, the closeness of the estimated values for
      d(3) in 2D and 3D is consistent with the possibility that d(3) is dimension
      independent. Generalizing the concept of the backbone, we introduce the concept
      of a "k-bone," which is the set of all points in a percolation system connected
      to k disjoint terminal points (or sets of disjoint terminal points) by k disjoint
      paths. We argue that the fractal dimension of a k-bone is equal to the fractal
      dimension of k-blocks, allowing us to discuss the relation between the fractal
      dimension of k-blocks and recent work on path crossing probabilities.

PMID- 12059667
TI  - Angular-momentum-induced phase transition in spherical gravitational systems: N
      body simulations.
AB  - The role of thermodynamics in the evolution of systems evolving under purely
      gravitational forces is not completely established. Both the infinite range and
      singularity in the Newtonian force law preclude the use of standard techniques.
      However, astronomical observations of globular clusters suggest that they may
      exist in distinct thermodynamic phases. Here, using dynamical simulation, we
      investigate a model gravitational system that exhibits a phase transition in the
      mean-field limit. The system consists of rotating, concentric, mass shells of
      fixed angular-momentum magnitude and shares identical equilibrium properties with
      a three-dimensional point mass system satisfying the same condition. The mean
      field results show that a global entropy maximum exists for the model, and a
      first order phase transition takes place between "quasi-uniform" and "core-halo"
      states, in both the microcanonical and canonical ensembles. Here we investigate
      the evolution and, with time averaging, the equilibrium properties of the
      isolated system. Simulations were carried out in the transition region, at the
      critical point, and in each clearly defined thermodynamic phase, and striking
      differences were found in each case. We find full agreement with mean-field
      theory when finite-size scaling is accounted for. In addition, we find that (1)
      equilibration obeys power-law behavior, (2) virialization, equilibration, and the
      decay of correlations in both position and time, are very slow in the transition
      region, suggesting that the system is also spending time in the metastable phase,
      and (3) there is a strong evidence of long-lived, collective oscillations in the
      supercritical region.

PMID- 12059668
TI  - Universality classes for self-avoiding walks in a strongly disordered system.
AB  - We study the behavior of self-avoiding walks (SAWs) on square and cubic lattices
      in the presence of strong disorder. We simulate the disorder by assigning random
      energy epsilon taken from a probability distribution P(epsilon) to each site (or
      bond) of the lattice. We study the strong disorder limit for an extremely broad
      range of energies with P(epsilon) is proportional to 1/epsilon. For each
      configuration of disorder, we find by exact enumeration the optimal SAW of fixed
      length N and fixed origin that minimizes the sum of the energies of the visited
      sites (or bonds). We find the fractal dimension of the optimal path to be
      d(opt)=1.52+/-0.10 in two dimensions (2D) and d(opt)=1.82+/-0.08 in 3D. Our
      results imply that SAWs in strong disorder with fixed N are much more compact
      than SAWs in disordered media with a uniform distribution of energies, optimal
      paths in strong disorder with fixed end-to-end distance R, and SAWs on a
      percolation cluster. Our results are also consistent with the possibility that
      SAWs in strong disorder belong to the same universality class as the maximal SAW
      on a percolation cluster at criticality, for which we calculate the fractal
      dimension d(max)=1.64+/-0.02 for 2D and d(max)=1.87+/-0.05 for 3D, values very
      close to the fractal dimensions of the percolation backbone in 2D and 3D.

PMID- 12059669
TI  - Dynamical phase transition of a one-dimensional kinetic Ising model with
      boundaries.
AB  - The Glauber model on a one-dimensional lattice with boundaries (for the
      ferromagnetic and antiferromagnetic cases) is considered. The large-time behavior
      of the one-point function is studied. It is shown that at any temperature, the
      system shows a dynamical phase transition. The dynamical phase transition is
      controlled by the rate of spin flip at the boundaries, and is a discontinuous
      change of the derivative of the relaxation time towards the stationary
      configuration.

PMID- 12059670
TI  - Phase diagram of the spin-3/2 Blume-Capel model in three dimensions.
AB  - We use a thermodynamically self-consistent theory to obtain the phase diagram of
      the ferromagnetic spin-3/2 Blume-Capel model on the simple cubic lattice. The
      theory is based on an Ornstein-Zernike approximation where the direct correlation
      function is truncated and the dependence upon the thermodynamic variables is
      determined by a set of two coupled partial differential equations. Within this
      framework, we localize the critical line in zero external field with high
      accuracy and in good agreement with previous Monte Carlo analysis. At low
      temperature, in contrast with Monte Carlo results, we find a first-order
      transition line ending at a critical end point whose coordinates are given by
      (k(B)T(c)/Jc=0.213+/-0.003,Delta(c)/Jc=0.491+/-0.001).

PMID- 12059671
TI  - Continuum percolation for randomly oriented soft-core prisms.
AB  - We study continuum percolation of three-dimensional randomly oriented soft-core
      polyhedra (prisms). The prisms are biaxial or triaxial and range in aspect ratio
      over six orders of magnitude. Results for prisms are compared with studies for
      ellipsoids, rods, ellipses, and polygons and differences are explained using the
      concept of the average excluded volume, <v(ex)>. For large-shape anisotropies we
      find close agreement between prisms and most of the above-mentioned shapes for
      the critical total average excluded volume, n(c)<v(ex)>, where n(c) is the
      critical number density of objects at the percolation threshold. In the extreme
      oblate and prolate limits simulations yield n(c)<v(ex)> approximately 2.3 and
      n(c)<v(ex)> approximately 1.3, respectively. Cubes exhibit the lowest-shape
      anisotropy of prisms minimizing the importance of randomness in orientation. As a
      result, the maximum prism value, n(c)<v(ex)> approximately 2.79, is reached for
      cubes, a value close to n(c)<v(ex)>=2.8 for the most equant shape, a sphere.
      Similarly, cubes yield a maximum critical object volume fraction of phi(c)=0.22.
      phi(c) decreases for more prolate and oblate prisms and reaches a linear
      relationship with respect to aspect ratio for aspect ratios greater than about
      50. Curves of phi(c) as a function of aspect ratio for prisms and ellipsoids are
      offset at low-shape anisotropies but converge in the extreme oblate and prolate
      limits. The offset appears to be a function of the ratio of the normalized
      average excluded volume for ellipsoids over that for prisms,
      R=<v(ex);>(e)/<v(ex);>(p). This ratio is at its minimum of R=0.758 for spheres
      and cubes, where phi(c(sphere))=0.2896 may be related to phi c(cube))=0.22 by
      phi(c(cube))=1-[1-phi(c(sphere))](R)=0.23. With respect to biaxial prisms,
      triaxial prisms show increased normalized average excluded volumes, <v(ex);>, due
      to increased shape anisotropies, resulting in reduced values of phi(c). We
      confirm that B(c)=n(c)<v(ex)>=2C(c) applies to prisms, where B(c) and C(c) are
      the average number of bonds per object and average number of connections per
      object, respectively.

PMID- 12059672
TI  - Exact finite-size corrections for the square-lattice Ising model with Brascamp
      Kunz boundary conditions.
AB  - Finite-size scaling, finite-size corrections, and boundary effects for critical
      systems have attracted much attention in recent years. Here we derive exact
      finite-size corrections for the free energy F and the specific heat C of the
      critical ferromagnetic Ising model on the Mu x 2 Nu square lattice with Brascamp
      Kunz (BK) boundary conditions [J. Math. Phys. 15, 66 (1974)] and compare such
      results with those under toroidal boundary conditions. When the ratio
      xi/2=(Mu+1)/2 Nu is smaller than 1 the behaviors of finite-size corrections for C
      are quite different for BK and toroidal boundary conditions; when ln(xi/2) is
      larger than 3, finite-size corrections for C in two boundary conditions approach
      the same values. In the limit Nu-->infinity we obtain the expansion of the free
      energy for infinitely long strip with BK boundary conditions. Our results are
      consistent with the conformal field theory prediction for the mixed boundary
      conditions by Cardy [Nucl. Phys. B 275, 200 (1986)] although the definitions of
      boundary conditions in two cases are different in one side of the long strip.

PMID- 12059673
TI  - Single-vehicle data of highway traffic: microscopic description of traffic
      phases.
AB  - We present a detailed analysis of single-vehicle data, which sheds some light on
      the microscopic interaction of the vehicles. Besides the analysis of free flow
      and synchronized traffic the data sets especially provide information about wide
      jams that persist for a long time. The data have been collected at a location far
      away from ramps and in the absence of speed limits, which allows a comparison
      with idealized traffic simulations. We also resolve some open questions
      concerning the time-headway distribution.

PMID- 12059674
TI  - Markov models from data by simple nonlinear time series predictors in delay
      embedding spaces.
AB  - We analyze prediction schemes for stochastic time series data. We propose that
      under certain conditions, a scalar time series, obtained from a vector-valued
      Markov process can be modeled as a finite memory Markov process in the
      observable. The transition rules of the process are easily computed using simple
      nonlinear time series predictors originally proposed for deterministic chaotic
      signals. The optimal time lag entering the embedding procedure is shown to be
      significantly smaller than the deterministic case. The concept is illustrated for
      simulated data and for surface wind velocity data, for which the deterministic
      part of the dynamics is shown to be nonlinear.

PMID- 12059675
TI  - Stepwise structure of Lyapunov spectra for many-particle systems using a random
      matrix dynamics.
AB  - The structure of the Lyapunov spectra for the many-particle systems with a random
      interaction between the particles is discussed. The dynamics of the tangent space
      is expressed as a master equation, which leads to a formula that connects the
      positive Lyapunov exponents and the time correlations of the particle interaction
      matrix. Applying this formula to one- and two-dimensional models we investigate
      the stepwise structure of the Lyapunov spectra that appear in the region of small
      positive Lyapunov exponents. Long range interactions lead to a clear separation
      of the Lyapunov spectra into a part exhibiting stepwise structure and a part
      changing smoothly. The part of the Lyapunov spectrum containing the stepwise
      structure is clearly distinguished by a wave-like structure in the eigenstates of
      the particle interaction matrix. The two-dimensional model has the same step
      widths as found numerically in a deterministic chaotic system of many hard disks.

PMID- 12059676
TI  - Oscillatory and chaotic dynamics in compartmentalized geometries.
AB  - The effects of spatial compartmentalization of a multistep reaction mechanism
      (Willamowski-Rossler model) whose mass action rate law shows oscillations and
      chaotic dynamics are explored. The mechanism is decomposed into subsets of
      reactions that are then assumed to take place in distinct regularly or randomly
      distributed spatial domains in the system. The reactive domains are coupled by
      diffusion. The spatiotemporal system states are investigated as a function of the
      system size and geometrical arrangement of the domains. A compartmentalization is
      chosen where the isolated domain attractors are simple steady states. It is then
      shown that changes in the system size or domain geometry can produce bifurcations
      leading to simple or period-doubled oscillatory attractors as well as chaotic
      states. These bifurcations are analyzed by direct simulations of the
      compartmentalized reaction-diffusion equations and by an analysis in terms of
      integral equations.

PMID- 12059677
TI  - Numerical study of eigenvector statistics for random banded matrices.
AB  - The statistics of eigenvector amplitudes near the band center in random-banded
      matrix ensembles is studied numerically. The nonlinear sigma model provides a
      rigorous description of the statistics in these ensembles. We are interested in
      the extension of the predictions of the sigma model approach to complex quantum
      systems. We study the validity range of the perturbation theory beginning from
      the well-known formulas in random matrix theory.

PMID- 12059678
TI  - Synchronization regimes of optical-feedback-induced chaos in unidirectionally
      coupled semiconductor lasers.
AB  - We numerically study the synchronization of two unidirectionally coupled single
      mode semiconductor lasers in a master-slave configuration. The master laser is an
      external-cavity laser that operates in a chaotic regime while for the slave laser
      we consider two configurations. In the first one, the slave laser is also an
      external-cavity laser, subjected to, its own optical feedback and the optical
      injection from the master laser. In the second one, the slave laser is subject
      only to the optical injection from the master laser. Depending on the operating
      conditions the synchronization between the two lasers, whenever it exists, can be
      either isochronous or anticipated. We perform a detailed study of the parameter
      regions in which these synchronization regimes occur and how small variations of
      parameter yield one or the other type of synchronization or an unsynchronized
      regime.

PMID- 12059679
TI  - Noise-enhanced phase locking in a chemical oscillator system.
AB  - Dynamical responses of a chemical oscillator to an external electric field were
      investigated in the Belousov-Zabotinsky reaction system with the catalyst
      Ru(bpy)(3)(2+) [tris-(2,2(')-bipyridine) ruthenium (II)] immobilized in cation
      exchange beads. Periodic forcing above the threshold induced phase locking, whose
      synchronization region has a shape similar to the Arnold tongue. When a certain
      amount of noise together with a subthreshold periodic signal was imposed on the
      chemical oscillator, 1:1 phase locking to the periodic signal occurred. Its
      degree passed through a maximum with increase in the noise intensity, a
      manifestation of stochastic resonance in the form of noise-enhanced phase
      locking. The experimentally observed features were reproduced in a numerical
      simulation with a forced Oregonator reaction-diffusion model.

PMID- 12059680
TI  - Planck's over 2 pi corrections in semiclassical formulas for smooth chaotic
      dynamics.
AB  - The validity of semiclassical expansions in the power of Planck's over 2 pi for
      the quantum Green's function have been extensively tested for billiards systems,
      but in the case of chaotic dynamics with smooth potential, even if formulas are
      existing, a quantitative comparison is still missing. In this paper, extending
      the theory developed by Gaspard et al. [Adv. Chem. Phys. 90, 105 (1995)], based
      on the classical Green's functions, we present an efficient method allowing the
      calculation of Planck's over 2 pi corrections for the propagator, the quantum
      Green's function, and their traces. In particular, we show that the previously
      published expressions for Planck's over 2 pi corrections to the traces are
      incomplete.

PMID- 12059681
TI  - Experimental study of dripping dynamics.
AB  - The dependence of dripping dynamics from physical properties of the nozzles is
      investigated. The analysis is performed by means of two complementary methods:
      (i) long dripping time series recorded with a standard laser-beam apparatus; and
      (ii) drop formations observed with a fast digital camcorder. Dripping from
      nozzles of different sizes is analyzed, and the formation of satellite drops is
      related to the preeminent physical parameter of control (flow rate). Quasielastic
      collisions between parent and satellite drops are observed.

PMID- 12059682
TI  - Lyapunov spectrum and synchronization of piecewise linear map lattices with power
      law coupling.
AB  - We study the synchronization properties of a lattice of chaotic piecewise linear
      maps. The coupling strength decreases with the lattice distance in a power-law
      fashion. We obtain the Lyapunov spectrum of the coupled map lattice and
      investigate the relation between spatiotemporal chaos and synchronization of
      amplitudes and phases, using suitable numerical diagnostics.

PMID- 12059683
TI  - Synchronization and information processing by an on-off coupling.
AB  - This paper proposes an on-off coupling process for chaos synchronization and
      information processing. An in depth analysis for the net effect of a conventional
      coupling is performed. The stability of the process is studied. We show that the
      proposed controlled coupling process can locally minimize the smoothness and the
      fidelity of dynamical data. A digital filter expression for the on-off coupling
      process is derived and a connection is made to the Hanning filter. The utility
      and robustness of the proposed approach is demonstrated by chaos synchronization
      in Duffing oscillators, the spatiotemporal synchronization of noisy nonlinear
      oscillators, the estimation of the trend of a time series, and restoration of the
      contaminated solution of the nonlinear Schrodinger equation.

PMID- 12059684
TI  - Transitions from partial to complete generalized synchronizations in
      bidirectionally coupled chaotic oscillators.
AB  - Generalized synchronization in an array of mutually (bidirectionally) coupled
      nonidentical chaotic oscillators is studied. Coupled Lorenz oscillators and
      coupled Lorenz-Rossler oscillators are adopted as our working models. With
      increasing the coupling strengths, the system experiences a cascade of
      transitions from the partial to the global generalized synchronizations, i.e.,
      different oscillators are gradually entrained through a clustering process. This
      scenario of transitions reveals an intrinsic self-organized order in groups of
      interacting units, which generalizes the idea of generalized synchronizations in
      drive-response systems.

PMID- 12059685
TI  - Chaotic scattering and the magneto-Coulomb map.
AB  - A nonrelativistic classical electron scattering by a fixed ion in a uniform
      magnetic field is discussed. The system is nonintegrable, and there is chaotic
      scattering for a certain class of initial conditions. A two-dimensional discrete
      map is derived from the equation of motion. Our map exhibits four different types
      of motion by changing the parameters which characterize the initial condition.
      The fractal structure for certain observables is obtained. The width of the
      chaotic scattering region in the impact parameter is estimated numerically. We
      suggest a certain class of plasma environments where the chaotic scattering may
      have an important role.

PMID- 12059686
TI  - Dynamical systems approach to Saffman-Taylor fingering: dynamical solvability
      scenario.
AB  - A dynamical systems approach to competition of Saffman-Taylor fingers in a Hele
      Shaw channel is developed. This is based on global analysis of the phase space
      flow of the low-dimensional ordinary-differential-equation sets associated with
      the classes of exact solutions of the problem without surface tension. Some
      simple examples are studied in detail. A general proof of the existence of finite
      time singularities for broad classes of solutions is given. Solutions leading to
      finite-time interface pinchoff are also identified. The existence of a continuum
      of multifinger fixed points and its dynamical implications are discussed. We
      conclude that exact zero-surface tension solutions taken in a global sense as
      families of trajectories in phase space are unphysical because the multifinger
      fixed points are nonhyperbolic, and an unfolding does not exist within the same
      class of solutions. Hyperbolicity (saddle-point structure) of the multifinger
      fixed points is argued to be essential to the physically correct qualitative
      description of finger competition. The restoring of hyperbolicity by surface
      tension is proposed as the key point to formulate a generic dynamical solvability
      scenario for interfacial pattern selection.

PMID- 12059687
TI  - Nearest-neighbor distribution for singular billiards.
AB  - The exact computation of the nearest-neighbor spacing distribution P(s) is
      performed for a rectangular billiard with a pointlike scatterer inside for
      periodic and Dirichlet boundary conditions, and it is demonstrated that when s-
      >infinity this function decreases exponentially. Together with the results of
      Bogomolny, Gerland, and Schmit [Phys. Rev. E 63, 036206 (2001)], it proves that
      spectral statistics of such systems is of intermediate type characterized by
      level repulsion at small distances and exponential fall-off of the nearest
      neighbor distribution at large distances. The calculation of the nth nearest
      neighbor spacing distribution P(n)(s) and its asymptotics is performed as well
      for any boundary conditions.

PMID- 12059688
TI  - Information theoretic approach to quantify complete and phase synchronization of
      chaos.
AB  - Based on an information theory approach we suggest a quantitative characteristic
      for evaluating the degree of chaotic synchronization. The proposed characteristic
      is tested for the cases of complete and phase synchronization of chaos. It is
      shown that this characteristic is stable with respect to the influence of small
      noise and nonlinear signal distortion.

PMID- 12059689
TI  - Fluctuations, convergence times, correlation functions, and power laws from many
      body Lyapunov spectra for soft and hard disks and spheres.
AB  - The dynamical instability of many-body systems is best characterized through the
      time-dependent local Lyapunov spectrum [lambda(j)], its associated comoving
      eigenvectors [delta(j)], and the "global" time-averaged spectrum [<lambda(j)>].
      We study the fluctuations of the local spectra as well as the convergence rates
      and correlation functions associated with the delta vectors as functions of j and
      system size N. All the number dependences can be described by simple power laws.
      The various powers depend on the thermodynamic state and force law as well as
      system dimensionality.

PMID- 12059690
TI  - Singularities in the fluctuation of on-off intermittency.
AB  - For a two-dimensional piecewise linear map exhibiting on-off intermittency, the
      scaling property of fluctuation, i.e., the large deviation property is
      investigated. It is shown that there are three phases of fluctuation and the q
      weighted average of an observed quantity has singularities such as jumps or a
      plateau due to transitions between the phases. At the onset of on-off
      intermittency, the width of the plateau vanishes due to the disappearance of one
      of the three phases and the singularity becomes weaker but more probable. The
      singularity at the onset of on-off intermittency is also examined on the coupled
      logistic map.

PMID- 12059691
TI  - Chaotic spectrum of a cavity resonator filled with randomly located sapphire
      particles.
AB  - We propose a new approach to the study of correlation properties of
      electromagnetic waves of a millimeter wave band after multiple passage through a
      random medium. The approach consists of an investigation of a spectrum of a
      cavity resonator, filled with randomly located dielectric inhomogeneities. As an
      object for the approach implementation, the spherical cavity resonator filled
      with sapphire particles, whose sizes are comparable to a wavelength, was chosen.
      It is revealed that the spectrum of this resonator in the frequency range 26 GHz
      38 GHz is chaotic. A number of correlation effects, such as the effect of
      "repulsion" of frequencies, the shape of the nearest-neighbor frequency spacing
      distribution close to the Wigner distribution, the characteristic curve of
      spectral rigidity, and the correlation of resonance lines on intensity and
      frequency were found in this spectrum. A superwide frequency band effect of the
      long retention of an energy of a short microwave impulse in a resonator is
      exposed and studied. We analyze features of the investigated chaotic spectrum on
      the basis of the conception of a spatial dispersion of effective dielectric
      permeability for a medial field in a medium filling the resonator. It is shown
      that this conception allows us to explain the complete elimination of the
      degeneration of a spectrum and its chaotization, and also the essential
      broadening of the resonance lines at the expense of the transfer of energy of
      dominant transverse modes to strongly damping longitudinal oscillations.

PMID- 12059692
TI  - Phase synchronization of chaotic attractors in the presence of two competing
      periodic signals.
AB  - We discuss the situation where two periodic signals compete to phase synchronize
      a chaotic attractor. Depending on the relative position of the periods with
      respect to the synchronization tongue for a single frequency signal, we
      distinguish several different cases. We find that, depending on parameters, it is
      possible that one or the other signal will entrain exclusively, or that they will
      entrain alternately, at their average frequency, or not at all.

PMID- 12059693
TI  - Quantum chaos in a ripple billiard.
AB  - We study the quantum chaos of a ripple billiard that has sinusoidal walls. We
      show that this type of ripple billiard has a Hamiltonian matrix that can be found
      exactly in terms of elementary functions. This feature greatly improves
      computation efficiency; a complete set of eigenstates from the ground state up to
      the 10,000th level can be calculated simultaneously. Nearest neighbor spacing of
      energy levels of a chaotic ripple billiard shows a Brody distribution (with a
      confidence level of 99% by chi(2) test) instead of the Gaussian orthogonal
      ensemble prediction. For high energy levels we observe scars and interesting
      patterns that have no resemblance to classical periodic orbits. Momentum
      localization of scarred eigenstates is also observed. We compare the scar
      associated localization with quantum dynamical Anderson localization by drawing
      the wave function distribution on basis state coefficients.

PMID- 12059694
TI  - Bayesian analysis of level-spacing distributions for chaotic systems with broken
      symmetry.
AB  - Bayesian inference is applied to the nearest-neighbor and next-nearest-neighbor
      spacing distributions of levels of coupled superconducting microwave billiards.
      The weakly coupled resonators are equivalent to a quantum system with a partially
      broken symmetry. The coupling parameters are obtained with help from Bayes's
      theorem. This procedure does not require the introduction of a set of bins. The
      results are more accurate than those obtained from other bin-independent
      procedures.

PMID- 12059695
TI  - Subharmonic bifurcations of standing wave lattices in a driven ferrofluid system.
AB  - Superlattice standing waves arising on the surface of ferrofluids that are driven
      by an ac magnetic field are investigated experimentally. Several different types
      are obtained through successive spatial period doublings, which are mediated by
      resonant mode interactions. The observed superlattices are quite diverse,
      depending on the relevant base Fourier modes, the orientation and the number of
      emerged subharmonic modes, and the phase difference among the involved modes all
      together. On the other hand, their temporal evolutions are all either period-1
      (harmonic) or period-2 (subharmonic).

PMID- 12059696
TI  - Speckle statistics in a chaotic multimode fiber.
AB  - Wave chaos is devoted to the study of wave motion when the geometrical limit of
      rays is chaotic. Imprints of ray chaos may be found either in spectral and
      spatial properties of modes or in spatio-temporal evolution of wave packets. In
      this paper, we present a thorough experimental and theoretical analysis of field
      statistics for light propagating in a multimode fiber with a noncircular cross
      section. This optical fiber serves as a powerful tool to image waves in a system
      where light rays exhibit a chaotic dynamics. We show that, in the speckle regime,
      the experimentally measured statistical properties of intensity patterns are well
      accounted for by a "random Gaussian" hypothesis. A comparison is also made in the
      case of regular ray motion by using a circular optical fiber. Possible extensions
      and applications of the tools and concepts of wave chaos are mentioned in modern
      communication technology.

PMID- 12059697
TI  - Rayleigh-Benard convection with an inclined upper boundary.
AB  - We report experiments on thermally driven convection of a high-Prandtl-number
      fluid with an inclined upper boundary. For an inclined angle greater than the
      critical value, we observed a few new convection patterns, in which laterally
      migrating convection cells and plumes appear simultaneously and a large-scale
      flow is induced from the inclined upper boundary. The plumes induced from the
      inclined upper boundary activate the temperature fluctuations, resulting in the
      formation of a large-scale horizontal heat transfer with a lateral scale larger
      than that of each convection cell. The critical angle for the onset of the
      lateral migration of the cells is determined by comparing the two length scales:
      the height difference in one convection cell imposed by the inclined upper
      boundary and the thickness of the viscous boundary layer.

PMID- 12059698
TI  - Effective velocity created by a point vortex in two-dimensional hydrodynamics.
AB  - We complete previous investigations on the statistics of velocity fluctuations
      arising from a random distribution of point vortices in two-dimensional
      hydrodynamics. We show that, in a statistical sense, the velocity created by a
      point vortex is shielded by cooperative effects on a distance Lambda
      approximately n(-1/2), the intervortex separation. For R>>Lambda, the "effective"
      velocity decays as R-2 instead of the ordinary law R(-1) recovered for R<<Lambda.
      These results are similar to those obtained by Agekyan [Sov. Astron. 5, 809
      (1962)] in his investigations on the fluctuations of the gravitational field.
      They give further support to our previous observation that the statistics of
      velocity fluctuations are (marginally) dominated by the contribution of the
      nearest neighbor.

PMID- 12059699
TI  - Formulation of a two-scale transport scheme for the turbulent mix induced by
      Rayleigh-Taylor and Richtmyer-Meshkov instabilities.
AB  - We develop a two-scale transport model for the turbulent mix induced by Rayleigh
      Taylor and Richtmyer-Meshkov instabilities. We generalize the buoyancy-drag model
      by adding an energy equation for a more complete description of the generated
      interpenetration between heavy and light fluids. The generalized buoyancy-drag
      model, in turn, provides an appropriate source to the two-equation turbulence
      model, which is most suited for the induced turbulent flows. The two-scale
      transport model has been validated and several illustrative examples will be
      presented.

PMID- 12059700
TI  - Probability density function of turbulent velocity fluctuations.
AB  - The probability density function (PDF) of velocity fluctuations is studied
      experimentally for grid turbulence in a systematical manner. At small distances
      from the grid, where the turbulence is still developing, the PDF is sub-Gaussian.
      At intermediate distances, where the turbulence is fully developed, the PDF is
      Gaussian. At large distances, where the turbulence has decayed, the PDF is hyper
      Gaussian. The Fourier transforms of the velocity fluctuations always have
      Gaussian PDFs. At intermediate distances from the grid, the Fourier transforms
      are statistically independent of each other. This is the necessary and sufficient
      condition for Gaussianity of the velocity fluctuations. At small and large
      distances, the Fourier transforms are dependent.

PMID- 12059701
TI  - Stationary spectrum of vorticity cascade in two-dimensional turbulence.
AB  - The logarithmic renormalization predicted by Kraichnan (1971) for the direct
      cascade of enstrophy in the inertial range of two-dimensional turbulence has been
      observed in a numerical simulation. A moderate resolution allows for a very long
      time integration that provides very good statistics. Deviations from Gaussianity
      in the vorticity probability distribution are observed.

PMID- 12059702
TI  - Mean wind and its reversal in thermal convection.
AB  - Properties of the mean wind in thermal convection, especially the abrupt reversal
      of its direction at high Rayleigh numbers, are studied. Measurements made in a
      closed cylindrical container of aspect ratio 1 are analyzed, and both the long
      term and short-term behaviors of the direction reversals are discussed. A first
      look at the data suggests a Brownian-type process in action, but a closer look
      suggests the existence of hierarchical features with time scales extending
      roughly over a decade and a half. A physical model consistent with experimental
      observations is presented, and the origin of the cutoff scales is discussed. It
      appears that the generation of the wind as well as the reversal of its direction
      can be understood in terms of the imbalance between buoyancy effects and
      friction.

PMID- 12059703
TI  - Effect of vorticity on second- and third-order statistics of passive scalar
      gradients.
AB  - The influence of vorticity on second- and third-order moments of the spatial
      derivatives of a forced, passive scalar field has been studied in the framework
      of a simplified problem; the analysis is restricted to dominating rotation and
      molecular diffusion is represented by a linear model. The results reveal that, in
      the case of a passive scalar experiencing forcing in an isotropic medium, both
      vorticity and diffusion counteract anisotropy imposed on the scalar field.
      Anisotropy at the level of second-order moments appears to be destroyed
      essentially by the action of vorticity.

PMID- 12059704
TI  - Hydrodynamic interactions in ordering process of two-dimensional quenched block
      copolymers.
AB  - The hydrodynamic coarsening of microphase separation in two-dimensional diblock
      copolymers is studied using numerical simulations. Results for symmetric and
      asymmetric block copolymers are compared. In contrast to the formation of the
      hexagonal phase where hydrodynamic flow appears not to be effective in enhancing
      domain coarsening, the late-time evolution of the lamellar phase proceeds faster,
      thus leading to a different power-law scaling with the addition of coupling of
      the velocity field to the order parameter.

PMID- 12059705
TI  - Rayleigh-Benard convection with rotation at small Prandtl numbers.
AB  - We present experimental and theoretical results near the onset of the Rayleigh
      Benard convection with rotation about a vertical axis in a fluid with a Prandtl
      number sigma close to 0.18. In the experiment we used a H2-Xe gas mixture with a
      separation ratio Psi=0.22 and a Lewis number L=1.22 at various pressures and
      dimensionless rotation rates Omega up to 400. On the basis of a standard weakly
      nonlinear stability analysis, we found a supercritical, stationary bifurcation
      for Omega < than approximately 13, which became subcritical over the range 13 <
      than approximately Omega < or approximately 160. For Omega > than approximately
      160 a supercritical Hopf bifurcation precedes the stationary instability of the
      uniform state. Following the unstable straight-roll fixed point in the
      subcritical regime by Galerkin methods we determined the location of the
      saddlenode and the stability of the nonlinear two-dimensional straight-roll
      state. The rolls were found to be unstable to three-dimensional Kuppers-Lortz
      perturbations for 3.8 < than approximately Omega < than approximately 160.
      Theoretical results for a pure fluid with the same sigma were qualitatively
      similar. Measurements using shadowgraph flow visualization yielded a bifurcation
      line and an Omega range of subcriticality, which agreed with the stability
      analysis. In the subcritical range the experiment revealed a discontinuity of the
      pattern amplitude at onset, but was unable to find any hysteresis. Patterns at
      onset fluctuated irregularly between the ground state and the finite-amplitude
      state. In this parameter range the convection pattern further above onset was
      chaotically time dependent. Investigation of the Hopf bifurcation line was
      difficult because of a wall mode that, for large Omega, preceded the bulk
      instability. For Omega approximately equal to 400, patterns were found in the
      sample interior only when the expected Hopf bifurcation was exceeded by about
      10%. This is consistent with the convective nature of the bifurcation. However,
      the observed structure, although time periodic, was spatially disordered and had
      a frequency that was considerably larger than the expected Hopf frequency. In a
      separate sample cell with a radial ramp in the spacing no structure was observed
      at all in the cell interior until the expected stationary instability was
      reached.

PMID- 12059706
TI  - Relation between pressure and fractional flow in two-phase flow in porous media.
AB  - We study average flow properties in porous media using a two-dimensional network
      simulator. It models the dynamics of two-phase immiscible bulk flow where film
      flow can be neglected. The boundary conditions are biperiodic, which provide a
      means of studying steady-state flow where complex bubble dynamics dominate the
      flow picture. We find fractional flow curves and corresponding pressure curves
      for different capillary numbers. In particular, we study the case of the two
      phases having equal viscosity. In this case we find that the derivative of the
      fractional flow with respect to saturation is related to the global pressure
      drop. This result can also be expressed in terms of relative permeabilities or
      mobilities, resulting in an equation tying together the mobilities of the two
      phases.

PMID- 12059707
TI  - Simulation of chemical erosion in rough fractures.
AB  - We report on numerical simulations of acid erosion in a fractured specimen of
      Carrara marble. The simulations combine two recent advances in lattice-Boltzmann
      methodology to accurately and efficiently calculate the velocity field in the
      pore space. A tracer diffusion algorithm was then used to calculate the
      distribution of reactants in the fracture, and the local erosion rate was
      obtained from the flux of tracer particles across the surfaces. Our results show
      that at large length scales, erosion leads to increased heterogeneity via channel
      formation, whereas at small length scales it tends to smooth out the roughness in
      the local aperture.

PMID- 12059708
TI  - Single relaxation time model for entropic lattice Boltzmann methods.
AB  - For lattice Boltzmann methods based on entropy functions, we derive a collision
      integral which enables simple identification of transport coefficients, and which
      circumvents construction of the equilibrium. Implementation of the two
      dimensional hydrodynamics demonstrates considerable increase of stability with
      respect to conventional lattice Boltzmann schemes.

PMID- 12059709
TI  - Soft-x-ray spectra of highly charged Kr ions in an electron beam ion trap.
AB  - Systematic variation of the electron-beam energy in the EBIT-II electron beam ion
      trap has been employed to produce soft-x-ray spectra (20-75 A) of Kr with well
      defined maximum charge states ranging from Cu- to Al-like ions. Guided by large
      scale relativistic atomic structure calculations, the strongest lines have been
      identified with Delta n=1 (n=3 to n(')=4) transitions from Ni- to P-like ions
      (Kr(8+)-Kr(21+)), as well as a number of 3p-4d and 3d-5f transitions.

PMID- 12059710
TI  - Effect of small amounts of hydrogen added to argon glow discharges: hybrid Monte
      Carlo-fluid model.
AB  - A hybrid Monte Carlo-fluid modeling network is developed for an argon-hydrogen
      mixture, to predict the effect of small amounts of hydrogen added to a dc argon
      glow discharge. The species considered in the model include the Ar gas atoms,
      electrons, Ar(+) ions and fast Ar atoms, ArH(+), H(+), H(2)(+) and H(3)(+) ions,
      and H atoms and H(2) molecules, as well as Ar metastable atoms, sputtered Cu
      atoms, and the corresponding Cu(+) ions. Sixty-five reactions between these
      species are incorporated in the model. The effect of hydrogen on various
      calculation results is investigated, such as the species densities, the relative
      role of different production and loss processes for the various species, the
      cathode sputtering rate and contributions by different bombarding species, and
      the dissociation degree of H(2) and the ionization degree of Ar and Cu. The
      calculation results are presented and discussed for 1% H(2) addition, and
      comparison is also made with a pure argon discharge and with only 0.1% H(2)
      addition.

PMID- 12059711
TI  - High-temperature electron localization in dense He gas.
AB  - We report accurate measurements of the mobility of excess electrons in high
      density helium gas in extended ranges of temperature [(26 < or = T < or = 77) K]
      and density [(0.05 < or = N < or = 10.0) atoms nm(-3)]. The aim is the
      investigation of the combined effect of temperature and density on the formation
      and dynamics of localized electron states. The main result of the experiment is
      that the formation of localized states essentially depends on the relative
      balance of fluid dilation energy, repulsive electron-atom interaction energy, and
      thermal energy. As a consequence, the onset of localization depends on the medium
      disorder through gas temperature and density. The transition from delocalized to
      localized states shifts to larger densities as temperature is increased. This
      behavior can be understood in terms of a simple model of electron self-trapping
      in a spherically symmetric square well.

PMID- 12059712
TI  - Experimental study of population inversion between excited states of Ar I in a
      recombining Ar plasma by He contact cooling.
AB  - An experiment of He gas contact for generating population inversion in a
      recombining Ar plasma jet is carried out. Population inversion between Ar I
      excited states 5s'-->4p'[1/2](1) and 5s'-->4p[3/2](1,2), [5/2](2,3) is created by
      helium gas-contact cooling of electrons, whereas it is not created without gas
      contact. Ar I lines 1.14, 1.34, and 1.09 microm are strongly enhanced due to the
      He gas cooling. It is experimentally found that helium gas contact effectively
      lowers the electron temperature of the Ar plasma jet. The mechanisms giving rise
      to population inversion are discussed in terms of atomic collisional processes of
      the recombining plasma. The experimental results of electron temperature and
      population densities are discussed by a simple numerical analysis that we
      previously developed. It is shown that the experimental results are well
      explained by our modeling quantitatively for the case without gas contact, except
      that the agreement of number densities of lower lying nonlocal-thermodynamic
      equilibrium levels is qualitative for the case with the gas contact.

PMID- 12059713
TI  - Experimental study of diffusive cooling of electrons in a pulsed inductively
      coupled plasma.
AB  - Langmuir probe measurements of the temporal behavior of the electron distribution
      function in a low-pressure inductive discharge are presented. The structure of
      the measured distribution functions suggests that the loss of high energetic
      electrons to the wall of the discharge chamber is the main energy loss mechanism.
      Electron-heavy-particle collisions play only a secondary role for the energy
      loss. The rapid loss of energetic electrons--while low energy electrons remain
      confined in the space charge potential field--leads to a fast cooling of the
      electron distribution function. We also present a simple model to describe the
      evolution of the mean kinetic energy and plasma potential on the basis of a
      distribution function that is cutoff at energies above the potential electron
      energy at the wall.

PMID- 12059714
TI  - Classical description of electron structure near a positive ion.
AB  - A single positive ion is imbedded in an electron gas with overall charge
      neutrality. A classical statistical mechanics is considered using an electron-ion
      Coulomb potential regularized at distances within the de Broglie length. The
      electron charge density and electric field distribution at the ion are studied as
      a function of ion-electron coupling using molecular dynamics simulation and
      theoretical models. Agreement between theory and simulation is quite good in
      general, although differences are observed for very strong ion-electron coupling
      due to the enhanced importance of close electron-ion configurations.

PMID- 12059715
TI  - Propagation of short intense laser pulses in gas-filled capillaries.
AB  - The guided laser pulse propagation and wake-field generation are studied in a
      wide (in comparison with the laser spot size) gas-filled capillary with an on
      axis gas density depletion, which can be produced by a rapid spin of the
      capillary around its axis or by radially propagating shock waves generated in a
      piezoceramic tube. A single equation for the wake-field potential, which
      describes the fully relativistic plasma response in the presence of optical field
      ionization (OFI) of a gas, is derived and used to demonstrate a guided
      propagation of a short intense laser pulse over many Rayleigh lengths in a leaky
      plasma channel produced by the pulse due to OFI in the capillary filled with a
      radially inhomogeneous gas. The efficient generation of a regular wake field over
      long distances suitable for the laser wake-field accelerators is shown.

PMID- 12059716
TI  - Resonant self-trapping of high intensity Bessel beams in underdense plasmas.
AB  - We present a comprehensive report based on recent work [Phys. Rev. Lett. 84, 3085
      (2000)] on resonant self-trapping and enhanced absorption of high power Bessel
      beams in underdense plasmas. The trapping resonance is strongly dependent on
      initial gas pressure, Bessel-beam geometry, and laser wavelength. Analytic
      estimates, and simulations using a one-dimensional Bessel-beam-plasma interaction
      code consistently explain the experimental observations. These results are for
      longer, moderate intensity pulses where the self-trapping channel is induced by
      laser-heated plasma thermal pressure. To explore the extension of this effect to
      ultrashort, intense pulsed Bessel beams, we perform propagation simulations using
      the code WAKE [Phys. Rev. E 53, R2068 (1996)]. We find that self-trapping can
      occur as a result of a plasma refractive index channel induced by the combined
      effects of relativistic motion of electrons and their ponderomotive expulsion.

PMID- 12059717
TI  - Theory of energy deposition by suprathermal electrons in laser-irradiated
      targets.
AB  - In this paper we describe results of the preheat generated by the suprathermal
      electrons from laser-produced plasmas in the cold substrate material. The
      computations were carried out by means of a Monte Carlo-type code that accounts
      for the scattering and slow down of the hot electrons in the cold material. Using
      ideas derived from a straight-line approximation method, the results were
      described by means of a dimensionless quantity. Such a description results in
      simple analytical (in fact, exponential) formulas, which are easy for computation
      and can be readily inserted into hydrodynamics codes. To exemplify the results,
      we have computed the preheat temperature and pressure in a laser-irradiated
      aluminum foil. A short discussion is given about the accuracy and the validity
      domain of the formulas, and a comparison is given to previous analytical methods.

PMID- 12059718
TI  - Multiterm spherical tensor representation of Boltzmann's equation for a
      nonhydrodynamic weakly ionized plasma.
AB  - The Boltzmann equation corresponding to a general "multiterm" representation of
      the phase space distribution function f(r,c,t) for charged particles in a gas in
      an electric field was reformulated entirely in terms of spherical tensors f(l)(m)
      some time ago, and numerous applications, including extension to time varying and
      crossed electric and magnetic fields, have followed. However, these applications
      have, by and large, been limited to the hydrodynamic conditions that prevail in
      swarm experiments and the full potential of the tensor formalism has thus never
      been realized. This paper resumes the discussion in the context of the more
      general nonhydrodynamic situation. Geometries for which a simple Legendre
      polynomial expansion suffices to represent f are discussed briefly, but the
      emphasis is upon cylindrical geometry, where such simplification does not arise.
      In particular, we consider an axisymmetric cylindrical column of weakly ionized
      plasma, and derive an infinite hierarchy of integrodifferential equations for the
      expansion coefficients of the phase space distribution function, valid for both
      electrons and ions, and for all types of binary interaction with neutral gas
      molecules.

PMID- 12059719
TI  - Observation of optical Smith-Purcell radiation at an electron beam energy of 855
      MeV.
AB  - Smith-Purcell radiation, generated when a beam of charged particles passes close
      to the surface of a diffraction grating, has been studied in the visible spectral
      range at wavelengths of 360 and 546 nm with the low emittance 855 MeV electron
      beam of the Mainz Microtron MAMI. The beam focused to a spot size of 4 microm
      (full width at half maximum) passed over optical diffraction gratings of echelle
      profiles with blaze angles of 0.8 degrees, 17.27 degrees, and 41.12 degrees and
      grating periods of 0.833 and 9.09 microm. Taking advantage of the specific
      emission characteristics of Smith-Purcell radiation a clear separation from
      background components, such as diffracted synchrotron radiation from upstream
      beam optical elements and transition radiation, was possible. The intensity
      scales with a modified Bessel function of the first kind as a function of the
      distance between electron beam and grating surface. Experimental radiation
      factors have been determined and compared with calculations on the basis of Van
      den Berg's theory [P.M. Van den Berg, J. Opt. Soc. Am. 63, 689 (1973)]. Fair
      agreement has been found for gratings with large blaze angles while the
      measurement with the shallow grating (blaze angle 0.8 degrees ) is at variance
      with this theory. Finally, the optimal operational parameters of a Smith-Purcell
      radiation source in view of already existing powerful undulator sources are
      discussed.

PMID- 12059720
TI  - Coherent synchrobetatron beam-beam modes: experiment and simulation.
AB  - Analytic calculation and numerical simulations reveal a multiline structure in
      the spectrum of coherent dipole oscillations in the colliding beam system due to
      coupled synchrobetatron beam-beam modes. The model employed in the analysis
      involves linearization of the beam-beam kick and takes into account the fact that
      the length of the colliding bunches is finite. In the present paper, we discuss
      the behavior of the synchrobetatron beam-beam modes, obtained both analytically
      and numerically, and compare it with the experimental results for the VEPP-2M
      collider. A particular case of the betatron tune close to the half-integer
      resonance is considered on the basis of the presented models.

PMID- 12059721
TI  - Nonlinear dynamics of periodically focused intense particle beams.
AB  - We extend a previous study [R. Pakter and F. B. Rizzato, Phys. Rev. Lett. 87,
      044801 (2001)] and investigate the nonlinear dynamics of periodically focused
      intense particle beams. We show that (i) the scenario as the focusing field
      increases is not the existence of a single threshold above which stable matched
      (equilibrium) solutions are absent, as believed so far, but the existence of
      successive regions of stability interrupted by gaps where periodic solutions are
      either unstable or simply do not exist; (ii) the beam can be focused to tighter
      radii using stable matched solutions found for focusing field strengths greater
      than the previous threshold. A comprehensive analysis is carried out as a
      function of the relevant parameters of the system. Self-consistent simulations
      validate the findings. The gaps are of crucial importance because they must be
      avoided if the goal is beam confinement with matched solutions; we develop an
      analytical model to determine the gap structure, which agrees well with computer
      simulations.

PMID- 12059722
TI  - Internal micropulse structure of a storage-ring free-electron laser.
AB  - The longitudinal distribution of a free-electron laser (FEL) may present a
      complex internal structure. This phenomenon has been already observed in the case
      of LINAC based oscillators and self-amplified spontaneous emission devices (for
      which the presence of "spikes" in the temporal distribution is systematically
      observed). We investigate here the physical process responsible for the growth of
      complex substructures inside the micropulse of a storage-ring free-electron
      laser. This "hole-burning-like" process results from the localized character of
      the interaction between the ultrarelativistic electron beam circulating in the
      storage ring and the laser pulse. Experimental results concerning the case of the
      super-ACO FEL are presented and interpreted by means of a pass-to-pass tracking
      code containing all the relevant features of the system dynamics.

PMID- 12059723
TI  - Synchrotron radiation from electron beams in plasma-focusing channels.
AB  - Spontaneous radiation emitted from relativistic electrons undergoing betatron
      motion in a plasma-focusing channel is analyzed, and applications to plasma wake
      field accelerator experiments and to the ion-channel laser (ICL) are discussed.
      Important similarities and differences between a free electron laser (FEL) and an
      ICL are delineated. It is shown that the frequency of spontaneous radiation is a
      strong function of the betatron strength parameter a(beta), which plays a role
      similar to that of the wiggler strength parameter in a conventional FEL. For
      a(beta) > or approximately 1, radiation is emitted in numerous harmonics.
      Furthermore, a(beta) is proportional to the amplitude of the betatron orbit,
      which varies for every electron in the beam. The radiation spectrum emitted from
      an electron beam is calculated by averaging the single-electron spectrum over the
      electron distribution. This leads to a frequency broadening of the radiation
      spectrum, which places serious limits on the possibility of realizing an ICL.

PMID- 12059724
TI  - Measuring and optimizing the momentum aperture in a particle accelerator.
AB  - Particle motion in storage rings is confined by various aperture limits, the size
      of which restricts the performance of the ring in terms of injection efficiency,
      lifetime, etc. Intrabeam scattering makes particles sweep a large portion of the
      phase space, where their motion may eventually be resonantly or chaotically
      excited to large amplitudes leading to collision with the vacuum chamber. We
      report here the studies performed at the Advanced Light Source (ALS) on the on-
      and off-momentum particle motion that provides a good understanding of these
      limitations. Using off-momentum simulations and experiments together with
      frequency map analysis, we could precisely correlate beam loss areas with
      resonance locations. The very good agreement between simulations and experiments
      allowed us to provide guidance for avoiding these dangerous areas. This analysis
      results in predictive improvements of the momentum aperture, which actually led
      to a lifetime increase of 25% at the ALS for very high bunch charge.

PMID- 12059725
TI  - Pulse propagation in a coupled resonator optical waveguide to all orders of
      dispersion.
AB  - In studying the propagation of optical pulses beyond the linear dispersion
      approximation, the conventional term-by-term Taylor series expansion of the
      waveguide dispersion relationship fails when applied to the recently introduced
      family of coupled resonator optical waveguides (CROWs). We have found the
      surprising result that retaining the complete form of the dispersion relationship
      in the tight-binding approximation does in fact lead to a closed form analytical
      solution, clearly highlighting the role of the various phenomenological factors.
      Such an analysis is usually not possible in the majority of waveguiding
      structures and is especially useful in the design of photonic crystal CROWs and
      deep superstructure Bragg gratings.

PMID- 12059726
TI  - Propagation properties of chirped soliton pulses in optical nonlinear Kerr media.
AB  - An investigation is made of the formation of a single soliton, or a pair of
      solitons, from initially nontransform limited pulses in a nonlinear Kerr medium
      having anomalous dispersion. A qualitative physical explanation is given for the
      formation of soliton pairs. Approximate solutions for the amplitudes and the
      velocities of the generated solitons are established and corroborated by
      numerical solutions of the Zakharov-Shabat eigenvalue problem.

PMID- 12059727
TI  - Soliton ratchetlike dynamics by ac forces with harmonic mixing.
AB  - The possibility of unidirectional motion of a kink (topological soliton) of a
      dissipative sine-Gordon equation in the presence of ac forces with harmonic
      mixing (at least biharmonic) and of zero mean, is presented. The dependence of
      the kink mean velocity on system parameters is investigated numerically and the
      results are compared with a perturbation analysis based on a point-particle
      representation of the soliton. We find that first order perturbative calculations
      lead to incomplete descriptions, due to the important role played by the soliton
      phonon interaction in establishing the phenomenon. The role played by the
      temporal symmetry of the system in establishing soliton dc motions that resemble
      usual soliton ratchets, is also emphasized. In particular, we show the existence
      of an asymmetric internal mode on the kink profile that couples to the kink
      translational mode through the damping in the system. Effective soliton transport
      is achieved when the internal mode and the external force get phase locked. We
      find that for kinks driven by biharmonic drivers consisting of the superposition
      of a fundamental driver with its first odd harmonic, the transport arises only
      due to this internal mode mechanism, while for biharmonic drivers with even
      harmonic superposition, also a point-particle contribution to the drift velocity
      is present. The phenomenon is robust enough to survive the presence of thermal
      noise in the system and can lead to several interesting physical applications.

PMID- 12059728
TI  - Dielectric structures with bound modes for microcavity lasers.
AB  - Cavity modes of dielectric microspheres and vertical cavity surface emitting
      lasers, in spite of their high Q, are never exactly bound, but have a finite
      width due to leakage at the borders. We propose types of microstructures that
      sustain three-dimensionally bound modes of the radiation field when dissipation
      is neglected. Unlike photonic crystals, the photonic systems that we consider
      here rely on periodicity in only one or two dimensions. In particular, we discuss
      a cavity composed of two crossed vertical layers combined with a periodic
      structure of horizontal layers. The layers have an anisotropic dielectric tensor,
      which could be obtained by making air holes in the vertical and horizontal
      directions within isotropic material. We calculate cavity resonance frequencies
      and spontaneous emission rates. The simplicity of this laser geometry allows an
      analytical study of light propagation and amplification in three dimensions.

PMID- 12059729
TI  - Relaxation properties of weakly coupled stochastic Ginzburg-Landau models under
      intense noise.
AB  - We investigate time relaxation properties of some correlation functions of
      stochastic Ginzburg-Landau models with weak coupling and under intense noise.
      Using a Feynman-Kac representation and a "high-temperature"-type approach, we
      study the low-lying spectrum of the generator of the dynamics, which determines
      the relaxation properties. We give the one-particle mass and energy-momentum
      dispersion curve, and also the two-particle bound-state mass, and show that both
      masses increase with the noise strength, in contrast with the behavior in the
      small noise regime.

PMID- 12059730
TI  - One- and two-dimensional solitons in second-harmonic-generating lattices.
AB  - In a model of a dynamical lattice with the on-site second-harmonic-generating
      nonlinearity and harmonic intersite couplings (that may be equal or different for
      the fundamental and second harmonics), various solitary-wave solutions are
      considered in one and two dimensions (1D and 2D). Fundamental (single-hump)
      solitons are identified in either dimension and their stability is examined and
      compared to previous results as well as to what is known for the model's
      continuum counterpart. Stability limits in terms of the coupling constants, which
      depend on the value of the phase-mismatch parameter, are found for solitons of
      the twisted-mode type in the 1D lattice, and for their counterparts of two
      different types (one being a discrete vortex) in the 2D lattice. When the twisted
      mode soliton is unstable, the instability, which may be either oscillatory or due
      to imaginary eigenfrequency pairs, transforms the unstable soliton into a stable
      fundamental one, in both 1D and 2D cases.

PMID- 12059731
TI  - Discrete solitons in nonlinear zigzag optical waveguide arrays with tailored
      diffraction properties.
AB  - We show that the discrete diffraction properties of a nonlinear optical zigzag
      waveguide array can be significantly modified, by exploiting the topological
      arrangement of the lattice itself. This introduces extended interactions (beyond
      nearest neighbors), which, in turn, affect the lattice dispersion relation within
      the Brillouin zone. As a result of this band alteration, we demonstrate that
      altogether different families of discrete soliton solutions are possible, which
      are stable over a wide range of parameters. In the regime where instabilities
      occur, all scenarios are considered in detail. By appropriately engineering the
      geometrical configuration of the array we find both standing and traveling
      diffraction-free beams. Our method opens opportunities for diffraction management
      that can be employed to generate low-power spatial discrete optical solitons.

PMID- 12059732
TI  - Phononic crystal with low filling fraction and absolute acoustic band gap in the
      audible frequency range: a theoretical and experimental study.
AB  - The propagation of acoustic waves in a two-dimensional composite medium
      constituted of a square array of parallel copper cylinders in air is investigated
      both theoretically and experimentally. The band structure is calculated with the
      plane wave expansion (PWE) method by imposing the condition of elastic rigidity
      to the solid inclusions. The PWE results are then compared to the transmission
      coefficients computed with the finite difference time domain (FDTD) method for
      finite thickness composite samples. In the low frequency regime, the band
      structure calculations agree with the FDTD results indicating that the assumption
      of infinitely rigid inclusion retains the validity of the PWE results to this
      frequency domain. These calculations predict that this composite material
      possesses a large absolute forbidden band in the domain of the audible
      frequencies. The FDTD spectra reveal also that hollow and filled cylinders
      produce very similar sound transmission suggesting the possibility of realizing
      light, effective sonic insulators. Experimental measurements show that the
      transmission through an array of hollow Cu cylinders drops to noise level
      throughout frequency interval in good agreement with the calculated forbidden
      band.

PMID- 12059733
TI  - Light scattering by optically anisotropic scatterers: T-matrix theory for radial
      and uniform anisotropies.
AB  - We extend the T-matrix approach to light scattering by spherical particles to
      some simple cases in which the scatterers are optically anisotropic.
      Specifically, we consider cases in which the spherical particles include radially
      and uniformly anisotropic layers. We find that in both cases the T-matrix theory
      can be formulated using a modified T-matrix ansatz with suitably defined modes.
      In a uniformly anisotropic medium we derive these modes by relating the wave
      packet representation and expansions of electromagnetic field over spherical
      harmonics. The resulting wave functions are deformed spherical harmonics that
      represent solutions of the Maxwell equations. We present preliminary results of
      numerical calculations of the scattering by spherical droplets. We concentrate on
      cases in which the scattering is due only to the local optical anisotropy within
      the scatterer. For radial anisotropy we find that nonmonotonic dependence of the
      scattering cross section on the degree of anisotropy can occur in a regime to
      which both the Rayleigh and semiclassical theories are inapplicable. For uniform
      anisotropy the cross section is strongly dependent on the angle between the
      incident light and the optical axis, and for larger droplets this dependence is
      nonmonotonic.

PMID- 12059734
TI  - Bistability of pulsating intensities for double-locked laser diodes.
AB  - Rate equations for semiconductor lasers subjected to simultaneous near-resonant
      optical injection and microwave current modulation are examined by combined
      analytical-numerical bifurcation techniques. Simple qualitative criteria are
      given for a bistable response. These results compare well with experimental
      measurements.

PMID- 12059735
TI  - Spatial nonparaxial correction of the ultrashort pulsed beam propagation in free
      space.
AB  - In this paper, a family of integral solutions representing ultrashort pulsed beam
      propagation in free space is studied by using the comoving frame coordinates and
      the Fourier transformation for time variable in terms of well-known paraxial
      approximation. The pulsed Gaussian-like beam solution is obtained as a special
      case of the integral solution, where the pulsed Gaussian beam solution is
      included. Further, starting from the nonparaxial pulsed beam propagation equation
      in the temporal-frequency domain and making use of the spatial Fourier transform,
      the nonparaxial pulsed beam solution is derived based on the paraxial pulsed beam
      solution, where the nonparaxiality is evaluated by a series of expansions.

PMID- 12059736
TI  - Propagation inhibition and wave localization in a two-dimensional random liquid
      medium.
AB  - Acoustic propagation and scattering in water containing many parallel air-filled
      cylinders is studied in an exact manner. Two situations are considered and
      compared; (1) wave propagating through the array of cylinders, imitating common
      experimental setups, and (2) wave transmitted from a source located inside the
      ensemble. We show that waves can be blocked from propagation by disorders in the
      first scenario, but such an inhibition does not necessarily lead to actual wave
      localization in the medium. The results indicate that the traditional method may
      be ambiguous in discerning localization effects. Furthermore, the results reveal
      the phenomenon of wave localization in a range of frequencies.

PMID- 12059737
TI  - Progressive motion of an ac-driven kink in an annular damped system.
AB  - A novel dynamical effect is presented: systematic drift of a topological soliton
      in ac-driven weakly damped systems with periodic boundary conditions. The effect
      is demonstrated in detail for a long annular Josephson junction. Unlike earlier
      considered cases of the ac-driven motion of fluxons (kinks), in the present case
      the long junction is spatially uniform. Numerical simulations reveal that
      progressive motion of the fluxon commences if the amplitude of the ac drive
      exceeds a threshold value. The direction of the motion is randomly selected by
      initial conditions, and a strong hysteresis is observed. An analytical approach
      to the problem is based on consideration of the interaction between plasma waves
      emitted by the fluxon under the action of the ac drive and the fluxon itself,
      after the waves complete round trip in the annular junction. The analysis
      predicts instability of the zero-average-velocity state of the fluxon interacting
      with its own radiation tails, provided that the drive's amplitude exceeds an
      explicitly found threshold. The result is valid if the phase shift phi of the
      radiation wave, gained after the round trip, is such that sin phi<0, the
      threshold amplitude strongly depending on phi. A very similar dependence is found
      in the simulations, testifying to the relevance of the analytical consideration.

PMID- 12059738
TI  - Photonic band structure of cholesteric elastomers.
AB  - We calculate the photonic band structure along and oblique to the helix axis of
      cholesteric elastomers. They are highly deformable, self-assembling systems. They
      display brilliantly colored reflections and lasing owing to stop bands in their
      photonic band structure. This band structure varies sensitively and extensively
      with strain. We show how additional stop bands open up and how they all shift in
      frequency. We predict a "total" stop band, that is, for both circular
      polarizations and show analytically how stop bands scale with strain. The
      extension of stop bands to a range of angles thereby creates pseudogaps, and the
      relevance to low-threshold lasing is discussed.

PMID- 12059739
TI  - Transit time of optical pulses propagating through a finite length medium.
AB  - We present experimental and theoretical results on the transit time of optical
      pulses propagating through bulk media of finite length, specifically GaAs and
      silica. The transit time of the peak of the pulse varies with the central
      wavelength due to the etalon effects caused by the reflectivity at the air/medium
      boundaries. For transform limited optical pulses, the transit time as a function
      of wavelength follows the transmittance spectrum, that is, the longest transit
      time occurs at the transmittance maxima where the cavity dwell time is the
      longest and the shortest transit time occurs at the transmittance minima. The
      results are dramatically different for chirped pulses obtained by modulating the
      injection current of a diode laser. The range in the transit times for chirped
      pulses is a factor of four times larger compared with transform limited pulses.
      In addition, the transit time for chirped pulses propagating through the GaAs
      sample is negative at certain wavelengths. Also, the transmitted pulse is not
      distorted. Although modulating the injection current of a diode laser is the most
      common method for generating optical pulses, to our knowledge this is the first
      reported observation of the transit time of these chirped optical pulses
      propagating through a simple etalon structure.

PMID- 12059740
TI  - Photonic Bloch oscillations and Wannier-Stark ladders in exponentially chirped
      Bragg gratings.
AB  - The formation of photonic Bloch oscillations and Wannier-Stark ladders is
      demonstrated in an exponentially chirped one-dimensional Bragg grating. The
      photonic Bloch oscillations are investigated using Hamiltonian optics, and direct
      analogies are made with electron dynamics in periodic potentials. The results of
      transfer matrix calculations are presented, which show the existence of a
      photonic Wannier-Stark ladder that should be detectable in experiments.

PMID- 12059741
TI  - Synchronization of chaos due to linear response in optically driven semiconductor
      lasers.
AB  - This paper presents physical aspects on chaos synchronization in semiconductor
      lasers (SLs) by studying synchronization from a fundamental standpoint of driven
      damped oscillators. We investigate the simple configuration, a chaotic master SL
      with optical feedback and a solitary slave SL. The point we emphasize is that the
      slave laser is regarded as a damped oscillator with relaxation oscillation.
      Linear stability analysis demonstrates that strong injection can enhance the
      damping of the slave SL. Consequently, the slave SL can have broad and nearly
      flat spectral characteristics in its driven response, which is sufficient for
      covering the broadband chaotic driving signal from the master SL. Numerical
      simulations verify that the slave SL subject to such strong injection
      synchronizes well with the chaotic driving signal. We consider that the
      synchronization phenomenon results from a quasilinear driven response of the
      slave SL with the remarkable spectral characteristics. Moreover, we discuss this
      type of chaos synchronization in comparison to anticipating-chaos synchronization
      occurring in our case from conventional complete synchronization theories, and
      clarify the different physical aspects of the chaos synchronization scheme. We
      also show that our analysis agrees well with the earlier experiments that could
      not have been explained by complete synchronization theory.

PMID- 12059742
TI  - Discrete vector spatial solitons in a nonlinear waveguide array.
AB  - A vector discrete diffraction managed soliton system is introduced. The vector
      model describes propagation of two polarization modes interacting in a nonlinear
      waveguide array with varying diffraction via the cross-phase modulation coupling.
      In the limit of strong diffraction we derive averaged equations governing the
      slow dynamics of the beam's amplitudes, and their stationary (in the form of
      bright-bright vector bound state) and traveling wave solutions are found. Through
      an extensive series of direct numerical simulations, interactions between
      diffraction-managed solitons for different values of velocities, diffraction, and
      cross-phase modulation coefficient are studied. We compare each collision case
      with its classical counterpart (constant diffraction) and find that in both the
      scalar and vector diffraction management cases, the interaction picture involves
      beam shaping, fusion, fission, nearly elastic collisions, and, in some cases,
      multihump structures. The collision scenario is found, in both the scalar and
      vector diffraction managed cases, to be rather different from the classical case.

PMID- 12059743
TI  - Resonant effects in compound diffraction gratings: Influence of the geometrical
      parameters of the surface.
AB  - We explore and discuss the influence of the geometrical parameters of a compound
      diffraction grating on the generation of pi resonances, which appear when the
      surface is illuminated by a p-polarized plane wave. We consider a grating with
      rectangular grooves, and analyze the evolution of pi resonances when depth,
      width, distance between grooves, and period of the grating are varied. In
      particular, we performed a detailed study for a grating with five grooves per
      period, and found that there are certain values of the geometrical parameters
      that optimize the enhancement of the electromagnetic field inside the
      corrugations. For an increasing depth of the grating, the resonant frequency
      verges on the value that corresponds to a finite grating. We also show numerical
      examples of the amplitude and phase of the electromagnetic field, where the
      differences in the near field for resonant and nonresonant configurations become
      apparent.

PMID- 12059744
TI  - Volumetric method for calculating the flow around moving objects in lattice
      Boltzmann schemes.
AB  - A method for calculating the fluid flow around moving objects is presented, based
      on a volumetric representation of the lattice-Boltzmann scheme and surfaces
      defined by facets. It enables us to move objects of arbitrary shape and
      orientation independent of the position of the grid nodes. To represent the
      motion of the object, additional momentum is added to the reflected particles
      from each facet in the propagation step. These particles are redistributed on
      nodes in the vicinity of the surface, depending on the position and orientation
      of the facet. Because the surface is considered to be closed, additional
      techniques need to be used to guarantee the conservation of mass. The flow field
      of a moving periodic cubic array of cubes at two Re numbers (Re=0.5 and Re=50) is
      compared with that of a fixed array. For Re=0.5, no significant deviations are
      found for the velocity field, pressure field, and the drag force. For Re=50, the
      drag and pressure field exhibit small fluctuations that relate to the position of
      the surface relative to the position of the grid. However, the influence of the
      pressure fluctuations on the velocity field is very small. Results on the
      velocity for a moving array of cubes show second-order accuracy in the lattice
      spacing. For physical consistency, the drag force on a periodic cubic array of
      moving spheres at Re=0.5 is compared with Hasimoto's analytical solution. The
      dependence on the grid spacing, the resolution of the surface of the object, and
      the viscosity have been studied. The discrepancies between simulations and the
      analytical results are smaller than 1.5%. For Re=50, the drag force, the
      streamline pattern, and the pressure field around a moving sphere in a large
      periodic domain showed good agreement with data from literature on a single
      sphere in an infinitely large flow field.

PMID- 12059745
TI  - Galilean-invariant lattice-Boltzmann simulation of liquid-vapor interface
      dynamics.
AB  - A two-dimensional two-phase lattice-Boltzmann model is presented and used for the
      study of interfacial phenomena under static and flow conditions. The model is
      based on the nonideal lattice-Boltzmann model proposed originally by Swift,
      Osborn, and Yeomans [Phys. Rev. Lett. 75, 830 (1995)] and makes it possible to
      couple a prescribed equation of state with the pressure tensor at the interface
      and the excess free-energy density formalism. The characteristic feature of the
      present model is that Galilean invariance is restored in the presence of
      interfaces without sacrificing any of the merits of the original model and,
      hence, the Navier-Stokes equation is adequately (to second order) recovered. The
      fluid properties can be prescribed in a thermodynamically consistent manner,
      which remains accurate at states close to the critical point. The model is first
      validated through static equilibrium tests and then applied to flow systems. It
      is shown that the simulator can reproduce some known two-phase flow
      configurations, like the motion of deformable droplets under the action of an
      external flow field. The simulator can also capture some interesting events
      during jet breakup and can be useful for the parametric study of the process in
      the two-dimensional case.

PMID- 12059746
TI  - Symplectic maps for approximating polynomial Hamiltonian systems.
AB  - We study how to approximate polynomial Hamiltonian systems by composition of
      symplectic maps. Recently, a number of methods preserving the symplectic
      character have appeared. However, they are not completely satisfactory because,
      in general, they are computationally expensive, very difficult to obtain or their
      accuracy is relatively low. The efficiency of a numerical method depends on both
      its computational cost and its accuracy. Polynomial Hamiltonians are separable in
      exactly solvable parts, and this can be done in many different ways. Here we
      study how to find a separation for the Hamiltonian in a small number of cheaply
      computed terms. Since the proposed methods depend on some free parameters, we
      also indicate how to choose these parameters in order to improve the accuracy
      without increasing the computational cost.

PMID- 12059747
TI  - Lattice Boltzmann method for viscoelastic fluids.
AB  - A lattice Boltzmann model for viscoelastic flow simulation is proposed. Elastic
      effects are taken into account within the framework of a Maxwell model. To test
      the approach, we estimate the transverse velocity autocorrelation function for a
      freely evolving system, and find clear manifestations of shear at large
      frequencies. We then characterize boundary-driven shear waves, and the resonant
      enhancement of shear oscillations in a periodically driven fluid confined within
      a capillary. The measured shear-wave dispersion relation is compared to that
      obtained from the Navier-Stokes equation with a Maxwell viscoelastic term, and
      good agreement is obtained.

PMID- 12059748
TI  - Entry ramps in the Nagel-Schreckenberg model.
AB  - This paper describes a way of including entry ramps in the Nagel-Schreckenberg
      traffic model. The idea is to place what are called shadow cars on a highway next
      to cars on entry ramps, which enables the drivers to take ramp cars into account.
      The model is shown to capture important real-life traffic phenomena that have not
      been included in previous models. Furthermore, it is demonstrated that the
      desirable properties of the Nagel-Schreckenberg model are retained.

PMID- 12059749
TI  - Optimized Verlet-like algorithms for molecular dynamics simulations.
AB  - Explicit velocity- and position-Verlet-like algorithms of the second order are
      proposed to integrate the equations of motion in many-body systems. The
      algorithms are derived on the basis of an extended decomposition scheme at the
      presence of a free parameter. The nonzero value for this parameter is obtained by
      reducing the influence of truncated terms to a minimum. As a result, the proposed
      algorithms appear to be more efficient than the original Verlet versions that
      correspond to a particular case when the introduced parameter is equal to zero.
      Like the original versions, the extended counterparts are symplectic and time
      reversible, but lead to an improved accuracy in the generated solutions at the
      same overall computational costs. The advantages of the optimized algorithms are
      demonstrated in molecular dynamics simulations of a Lennard-Jones fluid.

PMID- 12059750
TI  - Broken scaling in the forest-fire model.
AB  - We investigate the scaling behavior of the cluster size distribution in the
      Drossel-Schwabl forest-fire model (DS-FFM) by means of large scale numerical
      simulations, partly on (massively) parallel machines. It turns out that simple
      scaling is clearly violated, as already pointed out by Grassberger [P.
      Grassberger, J. Phys. A 26, 2081 (1993)], but largely ignored in the literature.
      Most surprisingly, the statistics do not seem to be described by a universal
      scaling function, and the scale of the physically relevant region seems to be a
      constant. Our results strongly suggest that the DS-FFM is not critical in the
      sense of being free of characteristic scales.

PMID- 12059751
TI  - Three-dimensional solutions of the Boltzmann equation: heat transport at long
      mean free paths.
AB  - A kinetic transport model for arbitrary meshes is presented and the method is
      applied to heat transfer in a rare gas between parallel plates at different
      temperatures. The method uses "propagating" rays for tracking the transport of
      particles throughout the phase space in three-dimensional spatial meshes. Two
      collision operators are tested with the model, a simple monoenergetic operator
      and the Bhatnagar-Gross-Krook (BGK) model. Results are generated for several
      Knudsen numbers in the transition regime. The results of the kinetic simulation,
      which employ the BGK operator, compare favorably with those of a finite
      difference solution of the Boltzmann equation using the BGK collision operator
      [T. Ohwada, Phys. Fluids 8, 2153 (1996)]. In addition, the results for both
      collision models exhibit fair agreement with experimental data of Teagan and
      Springer [Phys. Fluids. 11, 497 (1968)].

PMID- 12059752
TI  - Shortest paths on systems with power-law distributed long-range connections.
AB  - We discuss shortest-path lengths l(r) on periodic rings of size L supplemented
      with an average of pL randomly located long-range links whose lengths are
      distributed according to P(l) approximately l(-mu). Using rescaling arguments and
      numerical simulation on systems of up to 10(7) sites, we show that a
      characteristic length xi exists such that l(r) approximately r for r<xi but l(r)
      approximately r(theta(s)(mu)) for r>>xi. For small p we find that the shortest
      path length satisfies the scaling relation l(r,mu,p)/xi=f(mu,r/xi). Three regions
      with different asymptotic behaviors are found, respectively: (a) mu>2 where
      theta(s)=1, (b) 1<mu<2 where 0<theta(s)(mu)<1/2, and (c) mu<1 where l(r) behaves
      logarithmically, i.e., theta(s)=0. The characteristic length xi is of the form xi
      approximately p(-nu) with nu=1/(2-mu) in region (b), but depends on L as well in
      region (c). A directed model of shortest paths is solved and compared with
      numerical results.

PMID- 12059753
TI  - Combination of improved multibondic method and the Wang-Landau method.
AB  - We propose a method for Monte Carlo simulation of statistical physical models
      with discretized energy. The method is based on several ideas including the
      cluster algorithm, the multicanonical Monte Carlo method and its acceleration
      proposed recently by Wang and Landau. As in the multibondic ensemble method
      proposed by Janke and Kappler, the present algorithm performs a random walk in
      the space of the bond population to yield the state density as a function of the
      bond number. A test on the Ising model shows that the number of Monte Carlo
      sweeps required of the present method for obtaining the density of state with a
      given accuracy is proportional to the system size, whereas it is proportional to
      the system size squared for other conventional methods. In addition, the method
      shows a better performance than the original Wang-Landau method in measurement of
      physical quantities.

PMID- 12059754
TI  - Dependence on initial conditions of an adsorption-desorption process.
AB  - A one-dimensional irreversible adsorption-desorption process is simulated. The
      critical parameters as well as the critical exponents are measured. At the
      critical point, the crossover between the accumulative state and the depleted
      state is described by a universal characteristic function.

PMID- 12059755
TI  - Growing scale-free networks with small-world behavior.
AB  - In the context of growing networks, we introduce a simple dynamical model that
      unifies the generic features of real networks: scale-free distribution of degree
      and the small-world effect. While the average shortest path length increases
      logarithmically as in random networks, the clustering coefficient assumes a large
      value independent of system size. We derive analytical expressions for the
      clustering coefficient in two limiting cases: random [C approximately (ln
      N)(2)/N] and highly clustered (C=5/6) scale-free networks.

PMID- 12059756
TI  - One-dimensional Potts model, Lee-Yang edges, and chaos.
AB  - It is known that the exact renormalization transformations for the one
      dimensional Ising model in a field can be cast in the form of the logistic map
      f(x)=4x(1-x) with x a function of the Ising couplings K and h. The locus of the
      Lee-Yang zeros for the one-dimensional Ising model in the K,h plane is given by
      the Julia set of the logistic map. In this paper we show that the one-dimensional
      q-state Potts model for q> or =1 also displays such behavior. A suitable
      combination of couplings, which reduces to the Ising case for q=2, can again be
      used to define an x satisfying f(x)=4x(1-x). The Lee-Yang zeros no longer lie on
      the unit circle in the complex z=e(h) plane for q not equal 2, but their locus
      still maps onto the Julia set of the logistic map.

PMID- 12059757
TI  - Irrelevance of canonical or grand canonical constraints near a random fixed point
      in large L systems.
AB  - The equivalence between canonical and grand canonical constraints near a random
      fixed point in a critical disordered system is confirmed by means of Monte Carlo
      simulations. The slow approach to the asymptotic distribution for canonical
      averaging given by the L((alpha/nu)(random)) term is overcome by simulating long
      range correlated diluted Ising systems with (alpha/nu)(random)=(a-d) for the
      particular values a=2 (linear defects) and d=3 (three dimensional systems).

PMID- 12059758
TI  - Morphology from the maximum entropy principle: domains in a phase ordering system
      and a crack pattern in broken glass.
AB  - The maximum entropy principle is applied to study the morphology of a phase
      ordering two-dimensional system below the critical point. The distribution of
      domain area A is a function of ratio of the area to contour length L, R=A/L(A),
      and is given by exp(-lambda R(mu)) with exponent mu=2, which follows from the
      Lifshitz-Cahn-Allen theory. A and L are linked through the relation L
      approximately A(nu). We find two types of domain in the system: large of
      elongated shape (nu=0.88) and small of circular shape (nu=0.5). A crack pattern
      in broken glass belongs to the same morphology class with mu=1 and nu=0.72.

PMID- 12059759
TI  - Pattern formation on nonuniform surfaces by correlated random sequential
      absorptions.
AB  - The pattern formation on nonuniform surfaces by correlated-random sequential
      absorption (CRSA) process has been investigated by computer simulations. The
      nonuniform surfaces are represented by percolation clusters with probabilities
      p(s) and p(s) stands for the nonuniform degree of surfaces. The interactions
      between the particles and the defects in surfaces are involved by introducing a
      sticking coefficient s. When s-->0, the CRSA process is controlled by the
      absorption of surfaces and the correlation between particles. With the
      correlation increasing from a weak limit to a strong one, the cluster consisting
      of absorbed particles changes from the dispersed pattern of site percolation to
      correlated percolation, and then to Leath percolation clusters. When s-->1 and
      p(s)-->p(c), the CRSA process is dominated by the absorption of the defects,
      where p(c) is the threshold of percolations. The patterns appear randomly
      dispersed in spite of the correlation. With the decrease of s and increase of
      p(s), the interaction controlling the CRSA process changes from the absorption of
      defects to that of surface and the correlation between particles gradually. For
      the system s-->0, the transition correlation exponent alpha(c)=d(s), where d(s)
      is the fractal dimension of the percolation surfaces.

PMID- 12059760
TI  - Weakly pushed nature of "pulled" fronts with a cutoff.
AB  - The concept of pulled fronts with a cutoff epsilon has been introduced to model
      the effects of the discrete nature of the constituent particles on the asymptotic
      front speed in models with continuum variables (pulled fronts are the fronts that
      propagate into an unstable state, and have an asymptotic front speed equal to the
      linear spreading speed v* of small linear perturbations around the unstable
      state). In this paper, we demonstrate that the introduction of a cutoff actually
      makes such pulled fronts weakly pushed. For the nonlinear diffusion equation with
      a cutoff, we show that the longest relaxation times tau(m) that govern the
      convergence to the asymptotic front speed and profile, are given by tau(-1)(m)
      approximately equal to [(m+1)(2)-1]pi(2)/ln(2)epsilon, for m=1,2,....

PMID- 12059762
TI  - Modulation of localized states in electroconvection.
AB  - We report on the effects of temporal modulation of the driving force on a
      particular class of localized states, known as worms, that have been observed in
      electroconvection in nematic liquid crystals. The worms consist of the
      superposition of traveling waves and have been observed to have unique, small
      widths, but to vary in length. The transition from the pure conduction state to
      worms occurs via a backward bifurcation. A possible explanation of the formation
      of the worms has been given in terms of coupled amplitude equations. Because the
      worms consist of the superposition of traveling waves, temporal modulation of the
      control parameter is a useful probe of the dynamics of the system. We observe
      that temporal modulation increases the average length of the worms and stabilizes
      worms below the transition point in the absence of modulation.

PMID- 12059761
TI  - Effect of symmetry breaking on level curvature distributions.
AB  - We derive an exact general formalism that expresses the eigenvector and the
      eigenvalue dynamics as a set of coupled equations of motion in terms of the
      matrix elements dynamics. Combined with an appropriate model Hamiltonian, these
      equations are used to investigate the effect of the presence of a discrete
      symmetry in the level curvature distribution. An explanation of the unexpected
      behavior of the data regarding frequencies of acoustic vibrations of quartz block
      is provided.

PMID- 12059763
TI  - Tilted wave emission in optical parametric oscillators induced by a bichromatic
      pumping.
AB  - Tilted wave emission is found in a mean-field model of a degenerate optical
      parametric oscillator pumped by a bichromatic field with a frequency offset much
      smaller than the cavity free-spectral range. Tilted wave emission arises due to a
      nonadiabatic mechanism induced by the slow pump modulation, and disappears when
      either one of the two pump waves is blocked.

PMID- 12059764
TI  - Stabilization of ablative Rayleigh-Taylor instability due to change of the Atwood
      number.
AB  - Recent experiment [S.G. Glendinning et al., Phys. Rev. Lett. 78, 3318 (1997)]
      showed that the measured growth rate of laser ablative Rayleigh-Taylor (RT)
      instability with preheating is about 50% of the classic value and is reduced by
      about 18% compared with the simulated value obtained with the computer code
      LASNEX. By changing the temperature variation of the electron thermal
      conductivity at low temperatures, the density profile from the Bhatnagar-Gross
      Krook approximation is recovered in the simulation, and the simulated RT growth
      rate is in good agreement with the experimental value from Glendinning et al. The
      preheated density profile on ablative RT stablization is studied numerically. A
      change of the Atwood number in the preheating case also leads to RT
      stabilization. The RT growth formula gamma=square root of [Akg/(1+AkL)] - 2kV(a)
      agrees well with experiment and simulation, and is appropriate for the preheating
      case.

PMID- 12059765
TI  - Measuring and modeling thermal fluctuations at nanometer length scales.
AB  - The size of mechanical, electrical, and optical devices continues to be reduced.
      As the length scales of such devices decrease, coupling to the external
      environment greatly increases. Thermal fluctuations due to momentum exchange
      between air molecules and micron scale devices under ambient conditions can
      effect the dynamics of a system. To illustrate this we use an atomic force
      microscope cantilever and detection system to measure background noise and
      thermal fluctuations of a micron size beam. The beam is modeled by a Langevin
      type equation that is externally forced by a white-noise spectrum having an
      analytic as opposed to a statistical form. This model is compared with
      experimental data. It is found that at higher frequencies, a white-noise spectrum
      is not sufficient to model such a system. We modify the forcing spectrum so that
      it decays at higher frequencies and subsequently achieve closer agreement between
      the model and the experimental observations.

PMID- 12059766
TI  - Refractive index measurements in a reentrant isotropic-calamitic nematic phase
      transition.
AB  - In this work the temperature dependence of the extraordinary/ordinary refractive
      indices and optical birefringence are determined near the reentrant isotropic
      (I(RE))-calamitic nematic (N(C)) and N(C)-isotropic (I) phase transitions in a
      lyotropic mixture of potassium laurate, decanol, and water. This reentrant
      isotropic phase is verified by our experimental data and discussed in terms of
      thermal variation of the micellar shape anisotropy. The results showed also, with
      basis in the Vuks's equation, that near the maximum optical birefringence in the
      range of N(C) phase the extraordinary coefficient of electronic polarizability
      (phi(parallel)) is equal to the ordinary coefficient (phi( perpendicular)).

PMID- 12059767
TI  - Comment on "Deterministic equations of motion and phase ordering dynamics".
AB  - Zheng [Phys. Rev. E 61, 153 (2000)] claims that phase ordering dynamics in the
      microcanonical phi(4) model displays unusual scaling laws. We show here,
      performing more careful numerical investigations, that Zheng only observed
      transient dynamics mostly due to the corrections to scaling introduced by lattice
      effects, and that Ising-like (model A) phase ordering actually takes place at
      late times. Moreover, we argue that energy conservation manifests itself in
      different corrections to scaling.

PMID- 12059770
TI  - Models for protein folding and nature's choice of protein as catalyst.
AB  - The study of protein folding and unfolding pathways lends a fascinating dimension
      to protein biochemistry. Several models for protein folding have been postulated.
      Two powerful probes used in protein folding study are far UV-CD monitored stopped
      flow kinetics and pulse hydrogen exchange in conjunction with NMR. The formation
      of molten globule, which is an intermediate possessing secondary structure but
      not a well packed tertiary structure, is now emerging as a common feature on the
      folding pathway of many proteins. The molten globule is recognized by a class of
      molecules called chaperones which act as accelerators of protein folding. This
      article ends by elucidating why proteins are Nature's choice as catalysts.

PMID- 12059769
TI  - Structure and properties of small heat shock proteins (sHsp) and their
      interaction with cytoskeleton proteins.
AB  - The modern classification of small heat shock proteins (sHsp) is presented and
      peculiarities of their primary structure and the mechanism of formation of
      oligomeric complexes are described. Data on phosphorylation of sHsp by different
      protein kinases are presented and the effect of phosphorylation on oligomeric
      state and chaperone activity of sHsp is discussed. Intracellular location of sHsp
      under normal and stress conditions is described and it is emphasized that under
      certain condition sHsp interact with different elements of cytoskeleton. The
      literature concerning the effect of sHsp on polymerization of actin in vitro is
      analyzed. An attempt is made to compare effects of sHsp on polymerization of
      actin in vitro with the results obtained on living cells under normal conditions
      and after heat shock or hormone action. The literature concerning possible
      effects of sHsp on cell motility is also analyzed.

PMID- 12059771
TI  - Kinetics of thermal aggregation of tobacco mosaic virus coat protein.
AB  - The kinetics of thermal aggregation of coat protein (CP) of tobacco mosaic virus
      (TMV) have been studied at 42 and 52 degrees C in a wide range of protein
      concentrations, [P]0. The kinetics of aggregation were followed by monitoring the
      increase in the apparent absorbance (A) at 320 nm. At 52 degrees C the kinetic
      curves may be approximated by the exponential law in the range of TMV CP
      concentrations from 0.02 to 0.30 mg/ml, the first order rate constant being
      linearly proportional to [P]0 (50 mM phosphate buffer, pH 8.0). The analogous
      picture was observed at 42 degrees C in the range of TMV CP concentrations from
      0.01 to 0.04 mg/ml (100 mM phosphate buffer, pH 8.0). At higher TMV CP
      concentrations the time of half-conversion approaches a limiting value with
      increasing [P]0 and at sufficiently high protein concentrations the kinetic
      curves fall on a common curve in the coordinates [A/A(lim); t] (t is time and
      A(lim) is the limiting value of A at t --> infinity). According to a mechanism of
      aggregation of TMV CP proposed by the authors at rather low protein
      concentrations the rate of aggregation is limited by the stage of growth of
      aggregate, which proceeds as a reaction of the pseudo-first order, whereas at
      rather high protein concentrations the rate-limiting stage is the stage of
      protein molecule unfolding.

PMID- 12059772
TI  - Interaction of influenza A virus M1 matrix protein with caspases.
AB  - In this investigation, an ability of influenza A virus M1 matrix protein to bind
      intracellular caspases, the key enzymes of cell apoptosis, has been examined.
      Protein-protein binding on polystyrene plates and polyvinyl pyrrolidone membrane
      was employed for this purpose. Under a comparative study of caspases-3, -6, -7, 
      8 influenza virus M1 protein specifically bound caspase-8 and weakly bound
      caspase-7. Using a computer analysis of the N-terminal region of M1 protein, a
      site similar to the anti-caspase site of baculovirus p35 protein, which inhibits
      caspases and displays antiapoptotic activity, was identified. These results are
      in good agreement with the supposition that influenza virus M1 protein is
      involved in a caspase-8-mediated apoptosis pathway in influenza virus infected
      cells.

PMID- 12059773
TI  - Interaction of 65- and 62-kD proteins from the apical membranes of the Aedes
      aegypti larvae midgut epithelium with Cry4B and Cry11A endotoxins of Bacillus
      thuringiensis.
AB  - A protein with the molecular weight of 65 kD is the only component of Aedes
      aegypti larvae BBM capable to specifically bind mosquitocidal toxins Cry4B and
      Cry11A of Bacillus thuringiensis. This protein lacks the leucine aminopeptidase
      activity which is characteristic for the toxin-binding proteins from the
      membranes of caterpillars. Cry-toxins inactive against A. aegypti larvae either
      fail to bind to the 65-kD protein and to a putative product of its proteolysis
      with the molecular weight of 62 kD (Cry1Ab), or bind but do not compete for this
      binding with mosquitocidal proteins (Cry9A). The proteolytic splitting out of the
      first five alpha-helices in the Cry4B toxin molecule does not affect its binding
      to the 65- and 62-kD proteins, but an additional removal of 20-30 amino acids
      from the C-terminal of the molecule sharply spoils this binding. Monosaccharide
      residues are not involved in the binding of the 65- and 62-kD proteins with
      Cry4B, Cry11A, and Cry9A.

PMID- 12059775
TI  - A hydrophobic site on the surface of the angiotensin-converting enzyme molecule.
AB  - Using the hydrophobic fluorescent dye 8-anilino-1-naphthalenesulfonic acid (8
      ANS), a hydrophobic site on the surface of the protein globule of angiotensin
      converting enzyme (ACE) from bovine lung was found. The dissociation constant of
      the ACE-8-ANS complex was estimated as 1.5 +/- 0.2 microM. This hydrophobic site
      is far from the ACE catalytic sites because the binding of the hydrophobic dye
      does not influence ACE activity. Shielding of the ACE hydrophobic site due to the
      complex formation with 8-ANS or Triton X-100 resulted in pronounced stabilization
      of the enzyme against the action of water radiolysis products during gamma
      irradiation of dilute solutions of ACE.

PMID- 12059774
TI  - Effect of hydrogen peroxide on the activity and structure of Escherichia coli
      chaperone GroEL.
AB  - Chaperone GroEL was treated with different concentrations of hydrogen peroxide.
      The conformational states of GroEL were monitored by protein intrinsic
      fluorescence, 8-anilino-1-naphthalene sulfonate fluorescence, and far-UV CD
      measurements. The results show that GroEL has unusual ability to resist oxidative
      stress. GroEL kept its quaternary structure and activity even when treated with
      10 mM hydrogen peroxide. Two fragments were formed when GroEL was treated with
      high concentrations of hydrogen peroxide (more than 20 mM). It is suggested that
      GroEL, as a molecular chaperone, is related to oxidative process in vivo.

PMID- 12059776
TI  - Structure of the O-polysaccharide of Pseudomonas syringae pv. delphinii NCPPB
      1879(T) having side chains of 3-acetamido-3,6-dideoxy-D-galactose residues.
AB  - The O-polysaccharide (OPS) was obtained from the lipopolysaccharide of
      Pseudomonas syringae pv. delphinii NCPPB 1879(T) and studied by sugar and
      methylation analyses, Smith degradation, and (1)H- and (13)C-NMR spectroscopy.
      The OPS was found to contain residues of L-rhamnose (L-Rha) and 3-acetamido-3,6
      dideoxy-D-galactose (D-Fuc3NAc), and the following structure of the major (n = 2)
      and minor (n = 3) heptasaccharide repeating units of the OPS was established:
      [carbohydrate structure: see text]. The OPS is distinguished by the presence of
      oligosaccharide side chains consisting of three D-Fuc3NAc residues that are
      connected to each other by the (alpha 1-->2)-linkage. The OPS is characterized by
      a structural heterogeneity due to a different position of substitution of one of
      the four L-rhamnose residues in the main chain of the repeating unit as well as
      to the presence of oligosaccharide units with an incomplete side chain.

PMID- 12059777
TI  - Modeling the cascade of enzymatic reactions in liposomes including successive
      free radical peroxidation, reduction, and hydrolysis of phospholipid polyenoic
      acyls for studying the effect of these processes on the structural-dynamic
      parameters of the membranes.
AB  - Studies of the effect of primary products of free radical lipid peroxidation
      (LPO) on the structural-dynamic parameters of natural lipid-protein
      supramolecular complexes (biomembranes and blood serum lipoproteins) using
      standard inducers of radical processes in vitro (azo-initiators, transition metal
      ions, flavin oxidases, etc.) are impossible because of simultaneous production of
      numerous secondary LPO products that can induce structural changes. The data
      obtained suggest that phospholipid liposome microviscosity, as assessed by the
      extent of eximerization of the fluorescent probe pyrene, may significantly differ
      when oxidation is induced by animal C-15 lipoxygenase (yielding
      acylhydroperoxides only) and Fe(2+)-ascorbate system (resulting in simultaneous
      accumulation of primary and secondary LPO products). It is also shown that liver
      glutathione S-transferase can effectively reduce hydroperoxy-acyls in
      phospholipid liposomes and liver microsomes without their preliminary hydrolysis
      with phospholipase A(2). An enzymatic system is proposed for a cascade of
      enzymatic reactions simulating lipohydroperoxide metabolism in living cells,
      including successive free radical oxidation of phosphatidylcholine polyenoic
      acyls, reduction of their hydroperoxy-derivatives, and hydrolysis of fatty acid
      residues in the course of catalysis mediated by animal C-15 lipoxygenase,
      glutathione S-transferase, and phospholipase A(2), respectively.

PMID- 12059778
TI  - Effects of monovalent cations on phosphate accumulation and storage of the
      ectomycorrhizal fungus Suillus bovinus.
AB  - Comparative in vivo (31)P-NMR studies of the fungus Suillus bovinus (L.: Fr.) O.
      Kuntze in pure culture have produced interesting new data. To investigate the
      response of phosphate metabolism to a change in external monovalent cations,
      samples were exposed to a Hoagland solution containing different monovalent
      cations Li+, Na+, K+, or Rb+ at 10 mM concentration. A method of nutrient cycling
      during analysis where the cation was changed and the phosphate kept constant
      allowed us to determine the kinetics of phosphate accumulation, storage and
      incorporation into polyphosphate following exposure to the range of test cations.
      Different external monovalent cations had different effects upon changes in the
      content of both phosphate and polyphosphate. Treatment with Li+, Na+, or Rb+
      resulted in a change in phosphate accumulation to 60, 73, and 107% and in content
      of the intracellular mobile polyphosphate (polyP) to 119, 112, and 94%,
      respectively, compared with the control taken as 100%. The effect of each cation
      is related to its position in the periodic table. Reversing this process, i.e.,
      exchanging with K+, returned phosphate metabolism to normal. Although, the
      increase in depolarization of the cell membrane should affect the internal pH,
      fungal metabolism using energy requiring mechanisms appeared necessary to
      maintain the intracellular pH. Thus, increasing contents of mobile polyP were the
      consequence of an increasing energy demand. On the other hand, the increasing
      depolarization of the cell membrane following the sequence Rb+ < K+ < Na+ < Li+
      inhibited the net P(i) accumulation. Furthermore, it is postulated that the Pi
      accumulation was also regulated by the intracellular content in polyP.

PMID- 12059779
TI  - p-Chloromercuribenzoate-induced inactivation and partial unfolding of porcine
      heart lactate dehydrogenase.
AB  - Purified porcine heart lactate dehydrogenase was inactivated and partially
      unfolded with p-chloromercuribenzoate (pCMB). With the increase of pCMB/enzyme
      ratio the enzyme was gradually inhibited till almost completely inactivated at
      the pCMB/enzyme ratio of 20 : 1. Native polyacrylamide gel electrophoresis showed
      that with the increase of pCMB/enzyme ratio the bands of native enzyme decreased
      till completely vanished. Meanwhile inactive multiple bands emerged and became
      thicker, which implied that lactate dehydrogenase became loose. The
      conformational changes of the enzyme molecule modified with pCMB were followed
      using fluorescence emission, ultraviolet difference, and circular dichroism (CD)
      spectra. Increasing pCMB concentration resulted in the decrease of fluorescence
      emission intensity. The ultraviolet difference spectra of the enzyme modified
      with pCMB exhibited an increasing absorbance in the vicinity of 240 nm with the
      increasing concentration of the inhibitor. The changes of the fluorescence and
      ultraviolet difference spectra reflected the conformational changes of the
      enzyme. The CD spectrum changes of the enzyme showed that its secondary structure
      changed as well. These results suggest that pCMB not only inhibits this enzyme
      but also influences its conformation (partial unfolding).

PMID- 12059780
TI  - Isonicotinoylhydrazone analogs of isoniazid: relationship between superoxide
      scavenging and tuberculostatic activities.
AB  - Superoxide scavenging activity (SSA) of recently synthesized
      isonicotinoylhydrazones, analogs of the clinically used anti-tuberculosis drug
      isoniazid (INH), was investigated using xanthine/xanthine oxidase system to
      generate the superoxide anion. The isonicotinoylhydrazones exhibited well
      expressed SSA, whereas INH did not show any SSA. All of the
      isonicotinoylhydrazones had a tuberculostatic activity when tested with the
      standard strain of Mycobacterium tuberculosis H(37)R(v) and some of them had a
      higher tuberculostatic activity than INH. A lower acute toxicity was also
      observed compared to INH. Moreover, a correlation was observed between LD(50) and
      SSA for the isonicotinoylhydrazones studied. An explanation is suggested for the
      higher tuberculostatic activity and lower acute toxicity of some of the
      isonicotinoylhydrazones as compared to that of INH. A new route to less toxic
      derivatives of INH with potential tuberculostatic activity is proposed.

PMID- 12059781
TI  - The content and chain length of polyphosphates from vacuoles of Saccharomyces
      cerevisiae VKM Y-1173.
AB  - The content of inorganic polyphosphates (polyP) in vacuoles of the yeast
      Saccharomyces cerevisiae is approximately 15% of the total cellular polyP. Over
      80% of the vacuole polyP are in an acid-soluble fraction. It was first
      established by (31)P-NMR spectroscopy that a polymeric degree (n) of two
      subfractions obtained by precipitation with Ba(2+) in succession at pH 4.5 and
      8.2 was approximately 20 +/- 5 and 5 +/- 2 residues of ortho-phosphoric acid,
      respectively. Under a deficit of phosphate (P(i)) in the cultivation medium, the
      polyP content in vacuoles decreased approximately 7-fold with the same drastic
      reduction of their content in the cell. Unlike intact yeast cells, where polyP
      overcompensation is observed after their transfer from phosphate-free to
      phosphate-containing medium, the vacuoles do not show this effect. The data
      indicate the occurrence of special regulatory mechanisms of polyP synthesis in
      vacuoles differing from those in the whole cell.

PMID- 12059782
TI  - Dihydroceramide desaturase activity in tumors.
AB  - Dihydroceramide desaturase activity in the transplantable mouse hepatoma-22, rat
      hepatoma-27, M1 sarcoma, and RS1 rat cholangiocellular carcinoma has been
      investigated. It was found that the dihydroceramide desaturase activity in mouse
      hepatoma-22 is lower than that in normal mouse liver. However, the activity of
      this enzyme in subcutaneously and intrahepatically transplanted rat hepatoma-27
      is increased compared to normal value. Dihydroceramide desaturase activity in
      subcutaneously and intrahepatically transplanted M1 sarcoma as well as in
      hepatoma-27 is dependent on the tumor microenvironment. The enzyme activity in
      RS1 tumor was not revealed. The data indicate that dihydroceramide desaturase
      activity depends on the tumor type and its microenvironment.

PMID- 12059783
TI  - The immunological homunculus (immunculus) in normal state and pathology.
AB  - The immunculus is considered as the system (general network) of constitutively
      expressed natural autoantibodies against different extracellular, membrane,
      cytoplasmic, and nuclear self-antigens (ubiquitous and organ-specific). It is
      specially noted that the repertoires of natural autoantibodies are surprisingly
      constant in healthy persons, independent of gender and age, and characterized by
      only minimal individual peculiarities (individual immune fingerprints). On the
      other hand, abnormal metabolic changes which precede the clinical manifestation
      of different diseases showed easily detected changes, rather quantitative than
      qualitative, in the systems of natural autoantibodies in patients' sera
      (immunculus distortions). This phenomena could supposedly be used for "mapping"
      the state of physiological norm in terms of the millions of natural autoantibody
      repertoires, and for elaboration of the methods for early (preclinical) detection
      of potentially pathogenic metabolic changes. Could the individual features of the
      general network of constitutively expressed natural autoantibodies reflect the
      functional state of the body and be used for "mapping" of normal and pathological
      functional state? Could the changes in production of some biologically active
      natural autoantibodies not only reflect the state of the body, but be used for
      partial compensation of functional deficiency of certain molecular systems? These
      and related questions are discussed in this article. The research project
      "immunculus" is proposed for international cooperative investigations.

PMID- 12059784
TI  - Proinsulin C-peptide activates cAMP response element-binding proteins through the
      p38 mitogen-activated protein kinase pathway in mouse lung capillary endothelial
      cells.
AB  - Proinsulin C-peptide has been reported to have some biological activities and to
      be possibly involved in the development of diabetic microangiopathy. In the
      present study, we examined the effects of C-peptide on the mitogen-activated
      protein kinase pathway in LEII mouse lung capillary endothelial cells.
      Stimulation of the cells with C-peptide increased both p38 mitogen-activated
      protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2)
      activities and activity-related site-specific phosphorylation of the respective
      kinases in a concentration-dependent manner, but failed to activate c-Jun N
      terminal kinase. Stimulation of the cells with C-peptide also induced site
      specific phosphorylation of cAMP response element (CRE)-binding protein
      (CREB)/activating transcription factor 1 (ATF1), and thereby binding of these
      transcription factors to CRE. Among three CREB kinases tested, phosphorylation of
      mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2) was
      induced after stimulation with C-peptide. The phosphorylation of CREB, ATF1 and
      MAPKAP-K2 were inhibited by SB203580, a p38MAPK inhibitor, but not by PD98059, an
      ERK kinase inhibitor. These results indicate that C-peptide activates p38MAPK
      followed by MAPKAP-K2 to enhance DNA-CREB/ATF1 interactions.

PMID- 12059785
TI  - Genomic organization of the mouse peroxisome proliferator-activated receptor
      beta/delta gene: alternative promoter usage and splicing yield transcripts
      exhibiting differential translational efficiency.
AB  - Peroxisome proliferator-activated receptor (PPAR) beta/delta is ubiquitously
      expressed, but the level of expression differs markedly between different cell
      types. In order to determine the molecular mechanisms governing PPARbeta/delta
      gene expression, we have isolated and characterized the mouse gene encoding
      PPARbeta/delta. The gene spans approx. 41 kb and comprises 11 exons of which the
      six exons located in the 3'-end of the gene are included in all transcripts.
      Primer-extension and 5'-rapid amplification of cDNA ends experiments revealed the
      presence of multiple transcription start points and splice variants, originating
      from the use of at least four different promoters. One of these transcription
      start points was found to be used predominantly in all tissues examined.
      Initiation from this major transcription start point gives rise to a transcript
      with a 548 nt 5'-untranslated leader containing eight upstream AUG codons. We
      show that the presence of the 548 nt leader resulted in a low translational
      efficiency of the corresponding PPARbeta/delta mRNA and propose, based on
      structural features of the 5'-untranslated region, that translational initiation
      may be mediated via an internal ribosome entry site-dependent mechanism.

PMID- 12059786
TI  - A novel putative insect chitinase with multiple catalytic domains: hormonal
      regulation during metamorphosis.
AB  - We have used differential display to identify genes that are regulated by
      juvenile hormone in the epidermis of the beetle Tenebrio molitor. One of the
      genes encodes T. molitor chitinase 5 (TmChit5), a chitinase possessing an unusual
      structure. Sequence analysis of TmChit5 identified five 'chitinase units' of
      approx. 480 amino acids with similarity to chitinase family 18. These units are
      separated by less conserved regions containing putative PEST (rich in proline,
      glutamic acid, serine and threonine) sequences, putative chitin-binding domains
      and mucin domains. Northern-blot analysis identified a single transcript of
      approx. 9 kb, whose abundance correlated with that of 20-hydroxyecdysone during
      metamorphosis. Injection of pupae with 20-hydroxyecdysone alone, or in
      combination with cycloheximide, indicated that TmChit5 expression is directly
      induced by the hormone. Further experiments indicated that methoprene (a juvenile
      hormone analogue) indirectly induced TmChit5 mRNA expression. On the basis of the
      present results and previous studies, we propose a molecular mechanism for
      cuticle digestion during the moulting process.

PMID- 12059787
TI  - PrpE, a PPP protein phosphatase from Bacillus subtilis with unusual substrate
      specificity.
AB  - Bacillus subtilis is a Gram-positive bacterium with a relatively large number of
      protein phosphatases. Previous studies have shown that some Ser/Thr phosphatases
      play an important role in the life cycle of this bacterium [Losick and Stragier
      (1992) Nature (London) 355, 601-604; Yang, Kang, Brody and Price (1996) Genes
      Dev. 10, 2265-2275]. In this paper, we report the biochemical properties of a
      putative, previously uncharacterized phosphatase, PrpE, belonging to the PPP
      family. This enzyme shares homology with other PPP phosphatases as well as with
      symmetrical diadenosine tetraphosphatases related to ApaH (symmetrical Ap(4)A
      hydrolase) from Escherichia coli. A His-tagged recombinant PrpE was purified from
      E. coli and shown to have Ni(2+)-dependent and okadaic acid-resistant phosphatase
      activity against a synthetic phosphorylated peptide and hydrolase activity
      against diadenosine 5',5"'-tetraphosphate. Unexpectedly, PrpE was able to remove
      phosphate from phosphotyrosine, but not from phosphothreonine or phosphoserine.

PMID- 12059810
TI  - Chlamydia trachomatis infection in male partners of infertile couples: incidence
      and sperm function.
AB  - Chlamydia trachomatis infection is one of the most common sexually transmitted
      diseases. Its effect on male fertility, however, is still controversial. In this
      study, 284 male partners of infertile couples consulting the Center of Studies in
      Reproductive Biology (CEBRE) were analyzed. The incidence of C. trachomatis
      infection among male partners of infertile couples was 38.6%. There were no
      significant differences between infected and noninfected infertile men in any of
      the sperm parameters assessed (sperm concentration, motility and morphology). The
      results of the three bioassays developed to evaluate sperm physiology, namely
      spermatozoa-zona pellucida binding, acrosome reaction stimulated with human
      follicular fluid and zona-free hamster oocyte penetration, showed no differences
      between infected and noninfected men. Electron microscopy studies suggest that
      spermatozoa are active agents in the dissemination of the chlamydial infection;
      they could be acting as 'vehicles' for the pathogens. These, and other results,
      suggest that the possible effect of C. trachomatis on male fertility is not due
      to alterations in sperm 'quality' or function, but rather to the transmission of
      the disease to female partners, causing inflammatory processes and promoting the
      generation of antisperm antibodies.

PMID- 12059811
TI  - Late Lyme disease masking a non-functioning adenoma of the anterior lobe of the
      pituitary gland.

PMID- 12059788
TI  - A method for detection of overoxidation of cysteines: peroxiredoxins are oxidized
      in vivo at the active-site cysteine during oxidative stress.
AB  - Peroxiredoxins are often encountered as double spots when analysed by two
      dimensional electrophoresis. The quantitative balance between these two spots
      depends on the physiological conditions, and is altered in favour of the acidic
      variant by oxidative stress for all the peroxiredoxins we could analyse. Using
      HeLa cells as a model system, we have further analysed the two protein isoforms
      represented by the two spots for each peroxiredoxin. The use of selected enzyme
      digestion and MS demonstrated that the acidic variant of all the peroxiredoxins
      analysed is irreversibly oxidized at the active-site cysteine into cysteine
      sulphinic or sulphonic acid. Thus, this acidic variant represents an inactivation
      form of the peroxiredoxins, and provides a useful marker of oxidative damage to
      the cells.

PMID- 12059812
TI  - Does treatment of varicocele improve male fertility? results of the 'Deutsche
      Varikozelenstudie', a multicentre study of 14 collaborating centres.
AB  - Treatment of varicocele is suggested in infertile men if sperm parameter values
      are abnormal. The effectiveness of the treatment with respect to fertility
      remains to be clarified. A multicentre, prospective randomized study on
      varicocele treatment in infertile men to demonstrate the superiority of
      sclerotization of the varicocele in preventing persistence, was started in 1995
      with the collaboration of 15 German andrological centres. The primary endpoint
      was the incidence of pregnancy 1 year after randomisation. The number of cases
      needed to achieve the goal of the study was calculated at 460. However, three
      years after starting the study, only 67 patients had been randomized. Different
      reasons contributed to the poor recruitment. There was no significant increase in
      pregnancy rate in the treated group, compared to the controls, the confidence
      interval being 20.8% to 15.7%. The authors would like to encourage further
      collaborative study groups to start another prospective, randomized study with
      the aim of avoiding the costs and risks of varicocele treatment when its success
      remains unclear.

PMID- 12059813
TI  - Distribution and function of FSH receptor genetic variants in normal men.
AB  - Follicle stimulating hormone (FSH) plays a key role in the maintenance of
      qualitatively and quantitatively normal spermatogenesis. It controls gamete
      development through Sertoli cells, via binding to its receptor. The influence and
      importance of FSH receptor (FSHR) variants on Sertoli cell function is not
      completely understood and remains to be investigated. In this retrospective
      study, we explored the impact and action of two distinct FSHR isoforms,
      Thr307/Asn680 and Ala307/Ser680, in a large group of men. This investigation
      includes 288 normal healthy men, 86 of whom were proven fathers previously
      studied, and 202 were newly recruited subjects. The FSHR polymorphism at position
      680 was analyzed in the whole group, while position 307 was investigated in 150
      subjects, both of them by single-stranded conformation polymorphism (SSCP) gel
      electrophoresis. The distribution frequency for position 680 was 29% for the
      Asn/Asn, 52% for the Asn-Ser, 19% for the Ser-Ser variant, and for position 307,
      27% for the Thr-Thr, 55% for the Ala-Thr, 18% for the Ala-Ala, respectively.
      Polymorphism combinations that were different from Thr307/Asn680 - Ala307/Ser680
      were found in four subjects. When subjects were grouped according to genotype at
      position 680, no significant differences between basal FSH, testosterone, inhibin
      B levels and semen parameters were found. This clinical finding demonstrates
      that, differently from females, in whom a significant correlation between FSHR
      polymorphism and basal FSH levels was found, the FSHR genotype has no influence
      on clinical parameters in males.

PMID- 12059814
TI  - Hexanic Maca extract improves rat sexual performance more effectively than
      methanolic and chloroformic Maca extracts.
AB  - Lepidium meyenii (Maca) is traditionally employed in the Andean region for its
      supposed properties in improving fertility. The aim of this study was to
      determine the effect of subacute oral administration of hexanic, methanolic and
      chloroformic extracts of Maca root on sexual performance in inexperienced male
      rats. The following sexual performance parameters were evaluated: 1st mount, 1st
      intromission, ejaculation and post-ejaculatory latencies, intercopulatory
      interval and copulatory efficacy. All the tested fractions significantly
      decreased intromission latency and intercopulatory interval and increased
      intromission frequency and copulatory efficacy (P < 0.05) as compared to
      controls. Hexanic and methanolic extracts were able to increase mount frequency
      (MF), while only hexanic fraction significantly improved mount latency (ML)
      (P=0.038). Globally, only the hexanic fraction significantly improved the
      majority of the sexual parameters measured. Sub-acute oral administration of
      hexanic Maca extract improved sexual performance parameters in sexually
      inexperienced male rats most effectively.

PMID- 12059815
TI  - Primary culture of the rat epididymal epithelial cells as a source of oestrogen.
AB  - Studies were performed on the rat epithelial cells of the caput and cauda
      epididymidis cultured in a full medium enriched with foetal calf serum without or
      with exogenous testosterone. After 3 days of culture, the cells formed a
      monolayer. The cytoplasm of epididymal epithelial cells cultured with
      testosterone was rich in lipid droplets, glycogen and PAS-positive substances,
      while their content was decreased in the cytoplasm of cells cultured without
      testosterone. The activity of 3beta-hydroxysteroid dehydrogenase was observed
      both in the cytoplasm of cultured epididymal epithelial cells and epithelial
      cells of epididymal sections. Hormone assays showed very low levels of
      dehydroepiandrosterone, androstenedione and testosterone, and the absence of
      progesterone in the media of cells cultured without testosterone and higher
      testosterone concentrations when the cells were cultured with exogenous
      testosterone. However, the concentration of 17beta-oestradiol found in the medium
      of cells was high, and exceeded many-fold its levels in the control media.
      Lentaron (Formestan), steroidal inhibitor of cytochrome P450 aromatase added to
      the culture decreased the secretion of oestradiol. RT-PCR analysis yielded cDNA
      products of 333 bp in length when primers were chosen to amplify a highly
      conserved sequence in the 3' region of the cytochrome P450 aromatase gene. This
      study demonstrates the ability of epididymal epithelial cells in vitro to
      synthesize androgens and mRNA for cytochrome P450 aromatase in the cultured
      epididymal epithelial cells of the rat as well as the ability to aromatise the
      synthesized androgen to 17beta-oestradiol.

PMID- 12059816
TI  - Dexamethasone reduces acrosin activity of ram spermatozoa.
AB  - The aim of this study was to investigate the effect of dexamethasone on acrosin
      activity of spermatozoa in Chios rams during autumn (breeding season for sheep in
      Greece), in correlation with possible changes in blood testosterone.
      Dexamethasone was administered in four equal consecutive intramuscular
      injections, one every four hours (total dose: 3 mg kg(-1)). Total acrosin
      activity was determined in semen samples collected 48 h before and on the 4th and
      7th day and thereafter once every week until the 77th day after dexamethasone
      administration. Blood samples for testosterone radioimmunoassays were collected
      24 h before, during dexamethasone administration and on the 4th, 7th, 14th and
      21st day after administration. Total acrosin activity in spermatozoa was reduced
      between days 7-28 after dexamethasone administration. Dexamethasone also induced
      a reduction in mean value and basal level of blood testosterone and inhibited its
      episodic secretion between 1 and 4 days after administration. As the reduction of
      acrosin activity appeared relatively soon after dexamethasone administration (7th
      day), it is likely that the increased amount of dexamethasone did not influence
      the synthesis of proacrosin in the late spermatids. As glucocorticoid receptors
      exist in the epididymis and accessory glands in various species, dexamethasone
      may have a direct influence on the synthesis and/or release of acrosin inhibitors
      in epididymal fluid or seminal plasma. These changes in acrosin activity in ovine
      spermatozoa mediated by dexamethasone may be of importance regarding the role of
      stress in the reduction of sperm fertilizing ability.

PMID- 12059817
TI  - Cryptorchidism: seasonal variations in Greece do not support the theory of light.
AB  - To examine seasonal trends of cryptorchidism in Greece, 583 males with true
      isolated cryptorchidism were analyzed. All 208 912 live-born boys born during the
      same period were used as a comparison group. Seasonality by month of birth was
      evaluated using both Edwards' model with adjusted frequencies and exact theta(i),
      and Walter-Elwood method with exact theta(i). Both tests resulted in consistent
      findings. The incidence of cryptorchid births in Greece follows a documented
      cyclic pattern of simple harmonic type with spring being the season of
      statistical predominance (peak in March with a second, almost equivalent, peak in
      May). In contrast, in autumn the incidence of cryptorchid births was considerably
      lower (trough in September). Given the fact that no significant differences in
      daylight length are found among seasons in Greece, the detection of a significant
      seasonal variation suggests that factors other than light are involved in the
      pathogenesis of cryptorchidism. Low environmental temperature is proposed as a
      causative factor negatively influencing the maternal hCG profiles and the
      inguinoscrotal phase of testicular descent. This is further supported by: (i) the
      similarity of our results to those reported by other European countries of
      different longitude and geographical width and (ii) our data showing
      significantly smaller maternal hCG profiles at the 26th week of gestation during
      winter compared with summer.

PMID- 12059819
TI  - Emergency physicians: additional providers of emergency anaesthesia?

PMID- 12059820
TI  - The variable effect of low-dose volatile anaesthetics on the acute ventilatory
      response to hypoxia in humans: a quantitative review.
AB  - The purpose of this study was to review published studies (identified by a
      Medline-assisted search) on the effect of < or = 0.2 minimal alveolar
      concentration (MAC) halothane, isoflurane, enflurane and sevoflurane on the acute
      hypoxic ventilatory response in healthy subjects. Each article was examined for
      the anaesthetic agent, speed of hypoxic stimulus, background carbon dioxide and
      subject stimulation (audiovisual or painful). Analysis of variance was used to
      assess the significance of the influence of each of these factors on the
      standardised hypoxic response (the acute hypoxic ventilatory response in l.min(
      1) in the presence of anaesthetic, expressed as a fraction of the response
      without anaesthetic). There were 37 separate studies within 21 published
      articles. The main factor influencing standardised hypoxic response was
      anaesthetic agent (p < 0.002). A second influential factor was subject
      stimulation (p < 0.014), but the interaction term of agent and stimulation was
      also significant (p < 0.039), suggesting that the influence of stimulation varied
      with the agent used. Speed of hypoxia and background carbon dioxide had no
      influence. In contrast to previous authors' assertions that study conditions have
      a major impact on the acute ventilatory response to hypoxia, this review suggests
      that the main determinant is simply the anaesthetic agent used. The review also
      highlights important gaps in the research literature, which may direct future
      research in this field. In particular, it would seem important to investigate the
      influence of arousal when different anaesthetic agents are used.

PMID- 12059821
TI  - The effects of hypertonic saline solution (7.5%) on coagulation and fibrinolysis:
      an in vitro assessment using thromboelastography.
AB  - We studied the effects of hypertonic (7.5%) and normal saline on coagulation and
      fibrinolysis in an in vitro model using thromboelastography of human whole blood.
      Reaction times increased and alpha angles decreased with hypertonic saline
      replacement at 7.5% blood volume compared with similar dilution with normal
      saline. At 10% blood volume replacement with hypertonic saline, reaction and
      coagulation times were significantly increased and alpha angles were decreased.
      Clot lysis at 30 min was also significantly reduced. We conclude that 7.5%
      hypertonic saline solution has anticoagulant effects if it replaces 7.5% or more
      of blood volume.

PMID- 12059822
TI  - A comparison between midazolam co-induction and propofol predosing for the
      induction of anaesthesia in the elderly.
AB  - In a prospective, double-blind, randomised, placebo-controlled trial, we have
      compared the effects of midazolam co-induction with propofol predosing on the
      induction dose requirements of propofol in elderly patients. We enrolled 60
      patients aged > 70 years, attending for urological surgery. The patients were
      allocated randomly to one of three groups, to receive either midazolam 0.02
      mg.kg(-1), propofol 0.25 mg.kg(-1), or normal saline 2 ml (placebo) 2 min prior
      to induction of anaesthesia using propofol 1% infusion at 300 ml.h(-1). The
      propofol dose requirements for induction were recorded for two end-points (loss
      of verbal contact and insertion of an oropharyngeal airway). Cardiovascular
      parameters were recorded at 1-min intervals for each patient until induction was
      complete. The midazolam group showed a significant reduction in propofol dose
      requirements for induction (p = 0.05) compared to the placebo group. The propofol
      group did not show a significant dose reduction compared to placebo. There were
      no demonstrable differences in terms of improved cardiovascular stability between
      groups. We conclude that propofol predosing does not significantly reduce the
      induction dose of propofol required in the elderly, and there were no
      cardiovascular benefits to either midazolam co-induction or propofol predosing in
      the elderly.

PMID- 12059823
TI  - Measurement of systemic oxygen uptake during low-flow anaesthesia with a standard
      technique vs. a novel method.
AB  - We assessed agreement between measurement of systemic oxygen uptake using the
      Fick-derived method, and a novel method described by Biro, based on the
      difference in oxygen concentrations of the delivered fresh gas and the gas
      circulating in the circle system. Twenty-nine patients undergoing elective
      cardiac surgery were studied during stable haemodynamic and ventilatory
      conditions. Systemic oxygen uptake was measured using the two methods in each
      patient before and after cardiopulmonary bypass. Limits of agreement were found
      to be wide (-162 to 311 ml.min-1 before bypass, and -257 to 401 ml.min-1 after
      bypass), indicating poor agreement between the methods. No significant difference
      was found between the pre- and post cardiopulmonary bypass values for each
      method. We conclude that the Biro method, although attractive in terms of its
      simplicity, is an unreliable measure of systemic oxygen uptake under these
      conditions.

PMID- 12059824
TI  - Matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1 and tumour
      necrosis factor alpha release during cardiopulmonary bypass.
AB  - An inflammatory response occurs during cardiac surgery involving cardiopulmonary
      bypass. Matrix metalloproteinase-9 is an enzyme involved in cytokine processing
      and leucocyte extravasation. It is secreted as a pro-enzyme in response to
      several inflammatory mediators and is inhibited by endogenous tissue inhibitor of
      metalloproteinase-1. The interaction between matrix metalloproteinase-9 and its
      inhibitor during cardiopulmonary bypass is not known. We measured tumour necrosis
      factor alpha, and matrix metalloproteinase-9 and its inhibitor using enzyme
      immunoassay at three time points in 20 patients undergoing elective coronary
      artery bypass grafting with cardiopulmonary bypass. Tumour necrosis factor and
      matrix metalloproteinase concentrations increased in all patients during bypass
      (both p < 0.0001), whereas the inhibitor in contrast, decreased (p < 0.0001). We
      conclude that matrix metalloproteinase-9 is released as part of the inflammatory
      response during cardiac surgery. Levels of the endogenous inhibitor of
      metalloproteinase, however, show a different pattern of release, suggesting
      independent regulation.

PMID- 12059825
TI  - Monitoring pollution by proton-transfer-reaction mass spectrometry during
      paediatric anaesthesia with positive pressure ventilation via the laryngeal mask
      airway or uncuffed tracheal tube.
AB  - Twenty children aged 2-66 months were randomly allocated for airway management
      with either the laryngeal mask airway or uncuffed tracheal tube using
      intermittent positive pressure ventilation with a tidal volume of 8 ml.kg-1 and a
      respiratory rate adjusted to maintain end-expiratory carbon dioxide concentration
      at 5.3 kPa. Induction was with fentanyl/propofol and maintenance was with
      sevoflurane 2.5% in oxygen/air. The airway device was removed when the patients
      were awake and the patients were transferred to the postanaesthesia care unit 10
      min later. Air was sampled from a point 1.5 m above the floor at a location
      remote from the ventilation outlet and analysed using a proton-transfer-reaction
      mass spectrometer capable of continuous trace gas analysis at the parts per
      billion volume (ppbv) level. The concentration of sevoflurane was recorded every
      minute during three consecutive phases: for 5 min before the introduction of
      sevoflurane (background); after introduction of sevoflurane until removal of the
      airway device (intra-operative); and every minute after removal until the
      concentration returned to background levels. Median (interquartile range [range])
      intra-operative sevoflurane concentrations were 200-400 times higher than
      background values for the laryngeal mask airway 1 (1-2 [0-3]) ppbv vs. 404 (278
      523 [83-983]) ppbv, respectively, and the tracheal tube 2 (1-3 [0-5]) ppbv vs.
      396 (204-589 [107-1735]) ppbv (both p < 0.0001), and returned to background
      values within 5 min of removal. There were no differences in sevoflurane
      concentration between devices intra-operatively or after removal. The performance
      of the proton-transfer-reaction mass spectrometer was identical at the start and
      end of the 30-day study. We conclude that peri-operative sevoflurane
      concentration in a modern operating theatre is similar for the laryngeal mask
      airway and the uncuffed tracheal tube in paediatric patients receiving
      intermittent positive pressure ventilation. Intra-operative sevoflurane
      concentrations are five times lower than occupational safety limit requirements,
      and 1000 times lower 5 min after removal of the airway device with the patient
      awake. The proton-transfer-reaction mass spectrometer has potential for
      monitoring air quality in the operating theatre.

PMID- 12059826
TI  - John Snow, Thomas Wakley, and The Lancet.

PMID- 12059827
TI  - Off-pump coronary artery surgery.
AB  - Cardiopulmonary bypass has several associated deleterious effects that include a
      systemic inflammatory response, coagulopathy, central nervous system
      complications and a variable degree of end-organ damage. The recent upsurge in
      interest in "beating-heart" surgery attempts to avoid these deleterious effects.
      Advances in surgical technique, such as the use of intracoronary shunts and the
      Octopus retractor, have made beating-heart surgery a reality. The challenges for
      the anaesthetist are greater than for coronary artery surgery using
      cardiopulmonary bypass, and whilst some advantages are proven, such as the lack
      of the inflammatory response and the decreased need for blood or blood products,
      others have yet to be proved and there is a need for further research. The
      advantages and disadvantages need to be evaluated in randomised studies in order
      to confirm the safety and efficacy of these new techniques in terms of long-term
      graft patency and decreased morbidity.

PMID- 12059828
TI  - Leakage and absorption of isoflurane by different types of anaesthetic circuit
      and monitoring tubing.
AB  - Conductive rubber anaesthetic circuit tubing both absorbs volatile agents and
      leaks these agents through its walls. We quantified the leakage and absorption
      properties of the most commonly used plastic materials used to make breathing
      circuit tubing, relative to conductive rubber. We then compared two different
      types of plastic tubes used to carry gas to volatile agent monitors; one made of
      polyvinyl chloride, the other made of polyvinyl chloride lined internally with a
      thin layer of polyethylene. We found that the three commonly used plastic types
      used to make anaesthetic circuit tubing all leak less volatile anaesthetic
      through their walls than conductive rubber. Polyethylene and polypropylene tubing
      absorb significantly less volatile anaesthetic than conductive rubber; however,
      this is not the case with polyvinyl chloride tubing. Differences in the leakage
      and absorption properties of polyvinyl chloride monitoring tubing are not
      significantly changed by the addition of a thin internal layer of polyethylene.
      It is therefore not worthwhile incorporating this feature into production.

PMID- 12059829
TI  - Prediction by computerised tomography of distance from skin to epidural space
      during thoracic epidural insertion.
AB  - In this single group observational study on 29 patients, we describe a technique
      that predicts the depth of the epidural space, calculated from the routine pre
      operative chest computerised tomography (CT) scan using Pythagorean triangle
      trigonometry. We also compared the CT-derived depth of the epidural space with
      the actual depth of needle insertion. The CT-derived and the actual depths of the
      epidural space were highly correlated (r = 0.88, R2 = 0.78, p < 0.0001). The mean
      (95% CI) difference between CT-derived and actual depths was 0.26 (0.03-0.49) cm.
      Thus, the CT-derived depth tends to be greater than the actual depth by between
      0.03 and 0.49 cm. There were no associations between either the CT-derived or the
      actual depth of the epidural space and age, weight, height or body mass index.

PMID- 12059830
TI  - Consent for anaesthesia.

PMID- 12059832
TI  - Laryngeal mask obstruction.

PMID- 12059831
TI  - Coaxial breathing system outer tube occlusion: what goes in must come out.

PMID- 12059833
TI  - Tracheal tube cuff pressures.

PMID- 12059834
TI  - Consequences of cuff pressure.

PMID- 12059835
TI  - An unusual complication of suction through the tracheal tube.

PMID- 12059836
TI  - Awake fibreoptic-guided insertion of the ProSeal Laryngeal Mask Airway.

PMID- 12059837
TI  - A new device to reduce consumption of a halogenated anaesthetic agent.

PMID- 12059838
TI  - An unexpected finding.

PMID- 12059839
TI  - Spurious ventilator triggering in a dead patient.

PMID- 12059840
TI  - Management of mobile laryngeal tumours.

PMID- 12059842
TI  - Pharmacological management of bipolar depression.

PMID- 12059843
TI  - Schizophrenia in homeless persons: a systematic review of the literature.
AB  - OBJECTIVE: This article systematically reviews studies of prevalence of
      schizophrenia in homeless persons. METHOD: Medline and PsychInfo were searched
      using the key words: homeless person, mental illness, psychosis, and
      schizophrenia. The bibliographies of identified articles were also reviewed.
      RESULTS: Study designs varied considerably. The rate of schizophrenia in homeless
      persons reported in the 33 published reports, representing eight different
      countries, ranged from 2 to 45%. In the 10 methodologically superior studies, the
      prevalence range was 4-16% and the weighted average prevalence was 11%. In
      addition, rates were higher in younger persons, women and the chronically
      homeless. Slightly less than half of the homeless persons with schizophrenia were
      not currently receiving treatment. CONCLUSION: Schizophrenia is much more
      prevalent among homeless persons than in the population at large. Future research
      should focus on better ways of meeting the mental health care needs of homeless
      people with schizophrenia.

PMID- 12059844
TI  - Previous mood state predicts response and switch rates in patients with bipolar
      depression.
AB  - OBJECTIVE: The treatment of bipolar depression is a significant clinical problem
      that remains understudied. The role for antidepressant (AD) agents vs. mood
      stabilizers has been particularly problematic to ascertain. METHOD: Detailed life
      charting data from 42 patients with 67 depressive episodes were reviewed.
      Response rates and rates of switch into mania were compared based on the
      preceding mood state and on whether an AD or mood stabilizing (MS) agent was
      added following onset of depression. RESULTS: Patients who became depressed
      following a period of euthymia were more likely to respond to treatment (62.5%)
      than patients who became depressed following a period of mania or hypomania
      (27.9%). The ratio of response to switch for previously euthymic patients was
      particularly favorable. CONCLUSION: Mood state prior to onset of depression in
      bipolar disorder appears to be an important clinical variable that may guide both
      choice of treatment administered and expectation of outcome to treatment.

PMID- 12059845
TI  - Cognitive-based measures screening for depression in the medically ill: the DMI
      10 and the DMI-18.
AB  - OBJECTIVE: We suggest that the identification of depression in the medically ill
      (DMI) might be improved by focussing on cognitive features. METHOD: We recruited
      302 patients to complete our provisional cognitive-based measure. Subsets also
      completed one of two comparator screening measures, either the Hospital and
      Anxiety Depression Scale (HADS) or the Beck Depression Inventory for Primary Care
      (BDI-PC). One hundred and sixty patients were then assessed by a psychiatrist who
      estimated whether they were 'clinically depressed' and who also administered a
      standardized interview for depression (the CIDI). RESULTS: Analyses identified
      items discriminating clinically depressed and non-depressed individuals, allowing
      development of brief (10-item) and extended (18-item) measures. The two new
      measures were compared with the HADS and the BDI-PC in discriminating depressed
      and non-depressed medically ill patients. CONCLUSION: A cognitive construct-based
      approach to assessing depression in the medically ill appears strongly supported.
      We provide brief (DMI-10) and extended (DMI-18) measures that appear to have
      utility as screening instruments. Consideration of the discriminating items may
      also assist clinical decision making.

PMID- 12059846
TI  - Induction of mania and cycle acceleration in bipolar disorder: effect of
      different classes of antidepressant.
AB  - OBJECTIVE: To assess the effect of different antidepressants on induction of
      mania and cycle acceleration, commonly accepted unwanted effects of
      antidepressant treatment for acute bipolar depression. There is, however, the
      suggestion that certain classes of antidepressants may be less likely than others
      to cause these unwanted effects. METHOD: We conducted a prospective, open,
      naturalistic, life charting study to assess the occurrence of onset of mania and
      cycle acceleration attributable to two antidepressant classes: selective
      serotonin reuptake inhibitors (SSRIs) and bupropion. RESULTS: No difference was
      found between the two drug classes for either antidepressant-induced mania or
      cycle acceleration. Antidepressant-induced mania was much more likely to occur in
      bipolar I rather than bipolar II patients. The overall occurrence of induction of
      mania and cycle acceleration was low across antidepressant classes. CONCLUSION:
      These findings suggest that there is probably no difference in the risk of
      antidepressant-induced mania or cycle acceleration across commonly used classes
      of antidepressants for the treatment of bipolar depression.

PMID- 12059847
TI  - Negative symptoms in first episode non-affective psychosis.
AB  - OBJECTIVE: To determine the prevalence of negative symptoms and to examine
      secondary sources of influence on negative symptoms and the role of specific
      negative symptoms in delay associated with seeking treatment in first episode non
      affective psychosis. METHOD: One hundred and ten patients who met Diagnostic
      Statistical Manual-IV (DSM-IV) criteria for a first episode of schizophrenia
      spectrum psychoses were rated for assessment of negative, positive, depressive
      and extrapyramidal symptoms, the premorbid adjustment scale and assessment of
      demographic and clinical characteristics including duration of untreated
      psychosis (DUP). RESULTS: Alogia/flat affect and avolition/anhedonia were
      strongly influenced by parkinsonian and depressive symptoms, respectively. A
      substantial proportion (26.8%) of patients showed at a least moderate level of
      negative symptoms not confounded by depression and Parkinsonism. DUP was related
      only to avolition/anhedonia while flat affect/alogia was related to male gender,
      diagnosis of schizophrenia, age of onset and the length of the prodrome.
      CONCLUSION: Negative symptoms that are independent of the influence of positive
      symptoms, depression and extra pyramidal symptoms (EPS) are present in a
      substantial proportion of first episode psychosis patients and delay in seeking
      treatment is associated mainly with avolition and anhedonia.

PMID- 12059848
TI  - Use of illicit substances in a psychosis incidence cohort: a comparison among
      different ethnic groups in the Netherlands.
AB  - OBJECTIVE: Use of illicit substances has been suggested as an explanation for the
      increased incidence of psychosis among some immigrant groups. The aim of the
      present study is to compare the rates of illicit substance use among immigrants
      with a first psychosis with that among non-migrants. METHOD: A population-based,
      first-contact incidence study in the Netherlands. Patients and key informants
      were interviewed about drug use in the preceding year. RESULT: One hundred and
      eighty-one subjects were examined. Proportions of patients who misused any
      illicit substance were 23% for Dutch, 17% for Moroccans, 27% for Surinamese, 30%
      for Turkish subjects, and 33% for other immigrants. Logistic regression analysis,
      controlling for age and sex, showed that ethnicity did not significantly
      contribute to the prediction of substance misuse. CONCLUSION: A higher rate of
      drug misuse is an unlikely explanation for the increased incidence of psychotic
      disorders among Moroccan and Surinamese immigrants to the Netherlands.

PMID- 12059849
TI  - Life dissatisfaction as a predictor of fatal injury in a 20-year follow-up.
AB  - OBJECTIVE: To investigate the role of life satisfaction (LS) in fatal injuries
      with special references to unintentional injuries and whether health status
      modifies this relationship. METHOD: A sample of adult Finns unselected for health
      status (n=29 173) responded in 1975 to a LS scale. Nationwide registry for deaths
      was used. The dissatisfied were compared with the satisfied by Cox regression.
      RESULTS: During 1976-1995, 469 fatal injuries occurred, of which 235 were
      unintentional. Dissatisfaction predicted fatal unintentional [hazard ratio
      (HR)=2.83; 95% confidence interval (CI) 1.77-4.51] and intentional injury
      (HR=3.26; 2.01-5.30). The risk of fatal unintentional injury was 7.8-fold (women)
      and 4.0-fold (men) increased in the sick and dissatisfied compared with the
      healthy and satisfied. A repeatedly reported dissatisfaction (1975, 1981)
      provided a HR of 5.17 (1.48-18.0) for unintentional injury death during 1981
      1995. The found effect was partly mediated through health behavior and social
      situation. CONCLUSION: Life dissatisfaction predicts both unintentional and
      intentional injury death.

PMID- 12059850
TI  - Identifying crime victims who are at high risk for post traumatic stress
      disorder: developing a practical referral instrument.
AB  - OBJECTIVE: To construct a practical instrument for the identification and
      referral of crime victims who are at high risk for post traumatic stress disorder
      (PTSD). METHOD: Crime victims filing a complaint at a police station were asked
      to fill out a questionnaire probing risk factors for PTSD (n=126). One and 3
      months later, these victims filled out a self-report version of the PTSD Symptom
      Scale (PSS-SR). RESULTS: The combination of four items predicted persistent PTSD
      with a sensitivity of 1.00 and a specificity of 0.62. The items were: being
      victims of a violent crime, knowing the perpetrator, experiencing the results of
      the crime as worse than was expected, and blaming oneself for the event. Only 25%
      of PTSD cases received emotional support from a victim assistance organization.
      CONCLUSION: This study demonstrates that early detection of high-risk victims and
      their referral to treatment is both necessary and possible.

PMID- 12059851
TI  - The relationship between post-traumatic symptoms and life in exile in a clinical
      group of refugees from the former Yugoslavia.
AB  - OBJECTIVE: To investigate the association between life situation factors and post
      traumatic symptoms among refugees from the former Yugoslavia. METHOD: Twenty-six
      refugees from the former Yugoslavia were examined by the Harvard Trauma
      Questionnaire during psychiatric treatment, and 3 years later. At follow-up they
      also answered a questionnaire regarding their life situations. RESULT: A higher
      post-traumatic symptom level at follow-up was associated with a pattern of
      negative living conditions such as open unemployment, social isolation, and a
      high dependence on social welfare. Gender differences were found regarding the
      factors most related to symptom severity. CONCLUSION: The results indicate that a
      main problem in this patient group may be how to break vicious circles of high
      symptom levels and a poor life situation which suggests a need for integrated
      rehabilitation efforts.

PMID- 12059852
TI  - Nidotherapy: a new approach to the treatment of personality disorder.
AB  - OBJECTIVE: To develop a treatment, nidotherapy, or nest therapy, so named because
      it aims to alter the sufferer's personal environment rather than symptoms or
      behaviour, in the management of personality disorders. METHOD: Case studies, in
      which analysis of the environmental circumstances associated with the problems of
      personality disorder is followed by planned adjustment to that environment so
      that it makes a more appropriate fit for the personality. RESULT: Sustained
      improvement was found in two individuals with personality disorder after
      nidotherapy. Those with persistent and predictable personality attributes are
      easier in principle to treat than those with episodic or variable problems.
      CONCLUSION: Nidotherapy deserves further consideration in the management of
      personality disorders.

PMID- 12059854
TI  - The hypothesis of oestrogen withdrawal associated psychoses and the paradox of
      antipsychotic drug-induced hypoestrogenaemia.

PMID- 12059860
TI  - Growth factors in corneal wound healing following refractive surgery: A review.
AB  - The first part of this review article aims to provide important basic definitions
      of growth factor terminology, and to put forward a model for understanding the
      role of growth factors in a wound healing context. In the second part of the
      paper, we review the literature on growth factors in the cornea, including that
      on changes associated with wound healing following refractive surgery in the
      epithelial, stromal, and endothelial layers. The role of growth factors in
      stromal removal, corneal neovascularization, corneal innervation and wound
      healing is considered. The importance of the epithelial-stromal interaction is
      discussed, including the role of growth factors in keratocyte apoptosis. In the
      final section, we review the current literature on endogenous and exogenous
      modulation of growth factors in corneal wound healing. This includes important in
      vitro work but aims to emphasize clinically relevant results. Photorefractive
      keratectomy (PRK) may have short-term complications such as pain and haze,
      whereas laser in situ keratomilieusis (LASIK) may have longer-term adverse
      effects on corneal biomechanics. The emerging technique of laser epithelial
      keratomilieusis (LASEK) provides an interesting alternative wound which may be
      less susceptible to the inherent complications of PRK and LASIK. At present, the
      phenomenon of iatrogenic keratectasia following LASIK is not fully understood,
      but these features of wound healing following PRK may be amenable to growth
      factor modulation.

PMID- 12059862
TI  - Endophthalmitis following cataract surgery in Sweden. The 1998 national
      prospective survey.
AB  - PURPOSE: To investigate the morbidity of postoperative endophthalmitis (POE)
      following cataract surgery in Sweden in 1998. METHODS: Clinically presumed cases
      of POE were reported in a prospective survey in which all Swedish ophthalmic
      surgical units except one had agreed to participate. Data on intraocular cultures
      and visual outcomes at 3 months after infection were supplied. Surgical cases
      that became infected were identified in the Swedish National Cataract Register,
      thereby enabling screening for various putative risk factors. RESULTS: The
      nationwide incidence of POE amounted to 58 cases out of 54 666 cataract
      operations, or 0.1% of surgical cases. The predominant aetiology was gram
      positive bacteria, which comprised 57% of the material. Acrylic intraocular
      lenses were found to decrease the risk of POE significantly in comparison to
      hydrogel and polymethylmethacrylate lenses. CONCLUSIONS: The incidence of POE
      after cataract surgery in Sweden is similar to that currently reported elsewhere
      in the developed world. We hope that continued registration of cases of POE in
      Sweden will shed light on the possible influences of various prophylactic
      measures and different intraocular lens materials on the development of
      postoperative infection.

PMID- 12059861
TI  - The Swedish National Cataract Register: A 9-year review.
AB  - The Swedish National Cataract Register (NCR) has been collecting data on cataract
      extractions in Sweden since 1992. This unique national database now contains data
      pertaining to more than 400 000 operations, representing 93.4% of all operations
      performed nationwide during 1992-2000. Clinic participation in the NCR is
      voluntary. Tests have shown NCR data to be extremely reliable, while the
      participation of nearly all providers of cataract surgery in Sweden makes the
      data highly representative of cataract surgery throughout the country. The NCR
      collects pre- and per-operative data for every cataract extraction performed at
      participating clinics. Surgical outcome data and data about patients' self
      assessed visual function is collected in approximately 10% of cases. Since 1998,
      all cases of suspected postoperative endophthalmitis have also been reported to
      the NCR. The rate of surgery has increased from 4.47 to 7.26 per 1000 inhabitants
      during the period. Female subjects have constituted about 66% of all operated
      subjects each year and the mean age of patients has slowly increased from 75.2 to
      76.1 years. Average pre-operative visual acuity has improved each year. Second
      eye surgery has increased from 28.5% to 36.8% of all surgeries.
      Phacoemulsification has reached 98% as type of surgery (in 2000) and 92.7% of all
      intraocular lenses are foldable. Surgical outcome has improved by achieving a
      final refraction closer to the target refraction and less surgically induced
      astigmatism. The positive impact of cataract surgery in very elderly people has
      been demonstrated, as has the positive effect of second eye surgery, especially
      in young subjects. The NCR has served to enhance knowledge about trends and
      results of cataract surgery in Sweden. This review article describes some of the
      activities carried out and their results.

PMID- 12059863
TI  - Long-term visual outcomes in the Cataract-Free Zone Project in Brazil.
AB  - PURPOSE: To determine the long-term visual outcomes and causes of poor vision in
      the cataract population in Brazil treated in the Cataract-Free Zone Project.
      METHODS: Project A subjects (62 patients) were recruited in Taquaritinga, SP, 26
      months after surgery. Project B subjects (34 patients) were recruited in Sao Joao
      da Boa Vista, SP, 43 months after surgery. All patients underwent visual
      screening and eye examination (examination 1). They were classified according to
      visual acuity in the operated eye and the causes of poor vision were diagnosed
      and referred for treatment. The results of these interventions were collected
      (examination 2) and analysed by Chi-square test. RESULTS: At examination 1 in
      project A, 47 of 62 patients (75.6%) had visual acuity < or = 20/100. The main
      causes of poor vision were refractive error (31.9%) and posterior capsule
      opacification (17.0%), with or without refractive error. At examination 1 in
      project B, 22 of 34 patients (64.7%) had visual acuity < or = 20/100. The main
      causes of poor vision were again posterior capsule opacification (50.0%) and
      refractive error (9.0%). After posterior capsulotomy with Nd:YAG laser and
      prescription of new corrective eyeglasses, visual acuity = 20/80 was obtained in
      64.5% of patients in project A (OR = 0.18, CI = 0.07-0.41) and 70.5% of patients
      in project B (OR = 0.19, CI = 0.06-0.60) at examination 2. The causes of
      blindness in the remaining patients were identified. CONCLUSION: This type of
      project is effective in reducing blindness caused by cataracts in developing
      countries. However, long-term scheduled follow-up of operated patients is an
      effective means of avoiding consecutive blindness resulting from secondary
      cataracts and refractive changes.

PMID- 12059864
TI  - Long-term outcome of trabeculectomy in terms of intraocular pressure.
AB  - PURPOSE: To evaluate the outcome, long-term results and contributing prognostic
      factors of trabeculectomy in terms of intraocular pressure (IOP) and to compare
      the results in primary open-angle glaucoma (POAG) and exfoliation glaucoma (EG).
      METHODS: This study involved retrospective evaluation of 138 consecutive patients
      (138 eyes) with either POAG or EG. All patients had undergone primary
      trabeculectomy performed by the same surgeon between November 1994 and August
      1996. Only one eye per patient was included. Operations performed with the use of
      antimetabolites were excluded. All patients were aged over 40 years and were
      white. Follow-up for all subjects lasted at least 2 years. Successful control of
      IOP was defined as achieving IOP < or = 21 mmHg without medication (complete
      success) or with a single topical medication (qualified success). Success rates
      were determined using the Kaplan-Meier survival curve, and risk factors were
      analysed with proportional hazards regression. RESULTS: According to the Kaplan
      Meier survival curve, success rates (complete or qualified) were 82% at 1 year,
      70% at 2 years, 64% at 3 years and 52% at 4 years. A total of 63% were complete
      successes at 1 year, 54% at 2 years, 45% at 3 years and 40% at 4 years. Complete
      success rates were significantly better in the POAG group than in the EG group.
      Proportional hazards regression analysis showed that the presence of EG and early
      postoperative IOP > 30 mmHg decreased the possibility of complete success, while
      a cataract operation performed during follow-up improved it. CONCLUSION: The IOP
      reducing effect of trabeculectomy decreases gradually. After 4 years, 52% of
      operated eyes had IOP < or = 21 mmHg with or without a single topical medication.
      Diagnosis of EG implied a worse long-term outcome for trabeculectomy in terms of
      IOP.

PMID- 12059865
TI  - Comparison of the cardiovascular effects of unoprostone 0.15%, timolol 0.5% and
      placebo in healthy adults during exercise using a treadmill test.
AB  - PURPOSE: To compare the cardiovascular effects of unoprostone 0.15%, timolol 0.5%
      and placebo in healthy adults during exercise using a treadmill test. METHODS:
      Thirty subjects aged 18-37 years (mean age = 24.1 years) were randomized to one
      of six treatment sequences in a three-treatment, three-period crossover study
      (William's design). Study medication was instilled b.i.d. for 5 days before
      visits 2, 3, and 4. Between treatments, study medication was washed out for 9-10
      days. Each subject underwent a submaximal treadmill test at visits 2 through 4,
      15 min after dosing. RESULTS: After 15 min of exercise, average heart rates were
      143.1 +/- 21.2, 134.5 +/- 20.0 and 145.4 +/- 20.8 bpm for the unoprostone,
      timolol and placebo treatments, respectively. At no timepoint was there a
      statistically significant difference between the unoprostone and placebo
      treatments (p > 0.05). Beginning with the second minute of exercise, timolol
      produced a greater decrease in heart rate at all timepoints from placebo than
      unoprostone (p < 0.05). No consistent differences in systolic or diastolic blood
      pressure were observed between drug treatments (p > 0.05). CONCLUSIONS: Unlike
      timolol, unoprostone 0.15% does not reduce exercise-induced heart rate,
      indicating a lack of clinical effect on systemic beta-adrenergic receptors in
      young and healthy subjects.

PMID- 12059866
TI  - Cardiovascular effects of timolol maleate, brimonidine or brimonidine/timolol
      maleate in concomitant therapy.
AB  - PURPOSE: To examine the influence on maximal exercise performance in young
      healthy volunteers of timolol 0.5%, brimonidine 0.2% or placebo versus
      brimonidine 0.2% and timolol 0.5% used concomitantly. METHODS: The subjects in
      this prospective, double-masked, crossover comparison were dosed 15 min prior to
      treadmill testing. A period of 1 week was allowed between tests. RESULTS: The 20
      subjects who completed the trials (average age 24.5 +/- 7.4) had a mean maximum
      exercise heart rate of 196 +/- 12 bpm for placebo, 182 +/- 13 bpm for timolol,
      187 +/- 10 bpm for brimonidine, and 186 +/- 11 bpm for timolol/brimonidine
      concomitant therapy (p < 0.005). During recovery, the placebo group demonstrated
      a statistically higher systolic blood pressure (min 6) and pulse (mins 2 and 4)
      (p < 0.01). In addition, subjects treated with timolol/brimonidine demonstrated
      more premature contractions (atrial or ventricular) overall during exercise and
      recovery (p = 0.01). The brimonidine and concomitant treatment groups showed the
      greatest number of adverse events per subject, the most common of which were
      dizziness and fatigue (p = 0.031). CONCLUSION: This study suggests that both
      timolol and brimonidine, used alone and concomitantly, cause cardiovascular
      effects consistent with their pharmacology.

PMID- 12059867
TI  - Use of latanoprost to reduce acute intraocular pressure rise following neodymium:
      Yag laser iridotomy.
AB  - PURPOSE: To evaluate the efficacy of latanoprost in reducing acute intraocular
      pressure (IOP) elevation after neodymium:Yag laser iridotomy (LI). METHODS:
      Primary angle-closure glaucoma (PACG) eyes were randomized to receive
      premedication with latanoprost and pilocarpine or with pilocarpine only before
      LI. Postoperative IOP changes were compared with Wilcoxon signed-ranks test using
      the fellow eyes of 47 patients who had one eye in each group. RESULTS:
      Postoperative pressure spikes were significantly lower (p = 0.010) in the
      latanoprost group (4.1 +/- 5.0 mmHg) than in the control group (6.7 +/- 7.0
      mmHg). Mean elevation of IOP was less in the latanoprost group than in the
      control group at 1 hour (2.5 +/- 4.8 versus 4.1 +/- 4.7 mmHg, p = 0.013) and 2
      hours (0.8 +/- 5.6 versus 4.4 +/- 8.1 mmHg, p = 0.003) postoperatively. Eleven
      eyes in the latanoprost group (23.4%) and 20 eyes in the control group (42.6%)
      developed a rise in IOP > or = 6 mmHg (p = 0.048). CONCLUSION: Latanoprost may
      reduce the pressure rise following LI in PACG eyes, but its application is
      limited by a late onset of effect.

PMID- 12059868
TI  - Surgical decompression in traumatic optic neuropathy.
AB  - BACKGROUND: The management of traumatic optic neuropathy remains controversial.
      This retrospective study presents the results of 19 cases of indirect optic
      neuropathy where surgical decompression represented the primary mode of
      treatment. METHODS: Nineteen patients (20 optic nerves) with traumatic optic
      neuropathy underwent primary surgical decompression. The surgery was performed
      using the transethmoidal technique. RESULTS: The extent of bony optic canal
      injury documented during surgery indicated that this had been underestimated in
      this series by CT findings. Vision improved in eight patients, five of whom had
      had no light perception preoperatively. CONCLUSION: Primary surgical
      decompression of the optic nerve within 48 h of injury produces beneficial
      results. Testing of visual acuity 6 weeks after surgery does not serve as a
      reliable predictor of final outcome.

PMID- 12059869
TI  - A prospective study of children treated for retinoblastoma: cognitive and visual
      outcomes in relation to treatment.
AB  - PURPOSE: : To assess cognitive and visual outcomes in children treated for
      retinoblastoma. PATIENTS AND METHODS: A population-based group of 22 children
      treated for retinoblastoma were followed in a longitudinal, prospective study.
      Eleven children had unilateral tumours, all of which had been enucleated. The
      remaining 11 had bilateral tumours. Seven of these had undergone unilateral
      enucleation and local or external beam radiation to the other eye. Four children
      had been treated with local or external beam radiation only. Cognitive outcome
      and visual function was assessed at 4 and 6 years of age. RESULTS: We found no
      general delay in cognitive or motor development at 4 or 6 years of age. Better
      cognitive capacities were found in the bilateral/irradiated retinoblastoma
      patients than in unilateral/non-irradiated patients. However, two of the
      irradiated children, both of whom had been treated at 1 month of age, performed
      below group mean. None of the children was totally blind. Three children were
      visually impaired due to tumours affecting the macular area in the remaining eye;
      another three had subnormal visual acuity but no macular pathology. A total of 14
      children had been enucleated and had normal vision in the remaining eye. Visual
      fields and dark adaptation were adversely affected in a few cases, but colour
      vision was normal in all. CONCLUSION: Bilateral retinoblastoma seems to be
      associated with superior cognitive capacities. Few children were visually
      impaired according to WHO criteria. We speculate that children treated during the
      first months of life may be at risk of adverse cognitive and visual outcomes. The
      immature brain may be affected by radiation treatment, causing both cognitive and
      visual deviations.

PMID- 12059870
TI  - Optic nerve hypoplasia: Risk factors and epidemiology.
AB  - OBJECTIVES: To study the epidemiology of optic nerve hypoplasia. DESIGN AND
      METHODS: Children with optic nerve hypoplasia and visual impairment were
      identified through the Swedish Register of Visually Impaired Children. Pre- and
      perinatal characteristics were obtained from the Medical Birth Registry and by
      scrutinizing pregnancy and delivery records. Clinical characteristics of children
      with optic nerve hypoplasia are described. The following risk factors were
      studied: maternal age, parity, maternal smoking, gestational duration, birth
      weight, delivery method, Apgar score, maternal disease during pregnancy, drugs
      used in early pregnancy. RESULTS: Young maternal age, first parity, maternal
      smoking, preterm birth and factors associated with preterm birth were risk
      factors for optic nerve hypoplasia. There was an indicated association with the
      use of fertility drugs and antidepressant drugs. CONCLUSIONS: Optic nerve
      hypoplasia is apparently associated not only with other anomolies, notably of the
      central nervous system, but also with signs of general disturbance in fetal
      development.

PMID- 12059871
TI  - Electroretinographic oscillatory potentials in insulin-dependent diabetes
      patients: A long-term follow-up.
AB  - PURPOSE: The aim of this research was to study the relevance of long-term follow
      up of electroretinographic oscillatory potentials (OPs) in predicting the onset
      of minimal non-proliferative diabetic retinopathy in insulin-dependent diabetes
      patients. METHODS: A total of 80 insulin-dependent diabetics, with normal fundi
      and normal OPs at first examination, were followed prospectively for 10 years.
      Oscillatory potentials were measured and fundus examinations performed once or
      twice per year. RESULTS: During follow-up, 35% of patients developed diabetic
      retinopathy after a mean disease duration of 12 +/- 2 years. A decrease in OP
      amplitudes was seen in 46% of this group, but reductions were also seen in the
      25% of patients whose fundi remained normal. Statistical analysis of best-fit
      survival curves shows a significant difference (p < 0.001) in the point of Kaplan
      Meiers' curve maximal linearity (TmaxS). CONCLUSIONS: It appears that eyes with
      reduced OP amplitude have a greater probability of developing diabetic
      retinopathy. Subnormal OP amplitudes are not proof of real concomitant visible
      vascular damage, but may reflect a predisposition to functional neurosensorial
      disorder.

PMID- 12059872
TI  - A small number of older type 2 diabetic patients end up visually impaired despite
      regular photographic screening and laser treatment for diabetic retinopathy.
AB  - PURPOSE: The present study describes the prevalence of visual impairment and
      blindness in a geographically defined population 8 years after the introduction
      of a screening programme in 1987 for early detection of sight-threatening
      diabetic retinopathy. METHODS: Of 374 patients with diabetes, comprising 2.6% of
      the population in the study community, 72% were examined with fundus photography
      or biomicroscopy during 1994-95. These patients form the basis of this study. The
      screening programme was fulfilled by 93% of subjects, all of whom underwent
      ophthalmic examinations at least every other year. A total of 79 eyes in 52
      patients received photocoagulation for macular oedema alone or in combination
      with severe non-proliferative or proliferative retinopathy. RESULTS: Eight years
      after the implementation of the programme, only three patients, all with type 2
      diabetes (diabetes diagnosed at or after 30 years of age), had visual acuity < or
      = 0.1. The total number of eyes with visual acuity < or = 0.5 was higher in
      insulin-treated type 2 diabetic patients (n = 20) than in those on oral treatment
      (n = 5) or diet treatment only (n = 1) (p = 0.006 in both cases). The only
      independent risk factor for visual impairment in eyes with sight-threatening
      retinopathy was age. CONCLUSION: A small number of older type 2 diabetic patients
      end up with visual impairment due to unsuccessful photocoagulation of macular
      oedema.

PMID- 12059873
TI  - High dose intravenous methylprednisolone pulse therapy versus oral prednisone for
      thyroid-associated ophthalmopathy.
AB  - PURPOSE: To compare the effectiveness of intravenous (i.v.) methylprednisolone
      pulse therapy and oral prednisone when used as the initial treatment of patients
      with mild or moderate thyroid-associated ophthalmopathy. METHODS: Thirty-three
      consecutive patients with thyroid-associated ophthalmopathy in Helsinki and Turku
      University Hospitals were randomly assigned either i.v. methylprednisolone pulse
      therapy (group A, n = 18) or oral prednisone (group B, n = 15). Treatment
      outcomes were measured by subjective changes in the grade of diplopia and
      quantitatively in several ophthalmic variables at 3 and 12 months. Any decision
      to proceed with additional treatment at 3 months was made on clinical grounds.
      The study was open in respect of both the initial treatment and the need for
      additional therapy. RESULTS: No significant differences in the grade of diplopia,
      proptosis or soft tissue activity scores were noted between groups A and B from 0
      to 3 months. However, group A required additional forms of therapy at 3 months
      less frequently than did group B (p = 0.038). CONCLUSIONS: Our data suggest that
      i.v. methylprednisolone pulse therapy and oral prednisone are equally effective
      as initial treatments for thyroid-associated ophthalmopathy where diplopia,
      proptosis and signs of soft tissue inflammation are concerned. When additional
      treatment is required, i.v. methylprednisolone pulse therapy may be more
      effective than oral prednisone. However, the study's limitations meant that any
      decision to give additional treatment after the initial therapy was made on
      clinical grounds.

PMID- 12059874
TI  - Characterization of melanoma associated spongiform scleropathy.
AB  - PURPOSE: Melanoma associated spongiform scleropathy (MASS) describes areas within
      the sclera where collagen bundles appear to have disintegrated into loose fibres.
      It is found adjacent to choroidal and ciliary body melanoma. This study aimed to
      characterize these changes histopathologically. METHODS: Sections of 218 eyes
      that had been enucleated for malignant melanoma between January 1994 and June
      2000 were examined for MASS, using data collected from the files of the Eye
      Pathology Institute, University of Copenhagen. Findings were correlated to
      patient characteristics (age, gender and pre-enucleation radiation) and tumour
      characteristics (location, morphology and invasion). Staining was applied using
      haematoxylin-eosin (HE), periodic acid-Schiff (PAS), haematoxylin-phloxine
      saffron (HPS), alcian blue, colloidal iron and Masson's trichrome. Sixteen normal
      eyes and 29 eyes with diseases other than choroidal and ciliary body melanoma
      served as controls. RESULTS: Melanoma associated spongiform scleropathy was
      observed in 73 of the 218 eyes (33%) with melanoma. No changes were found in
      normal eyes or in eyes with other intraocular diseases. A significantly higher
      incidence of MASS was found in older age groups. Thirty-six (49%) of the 73 cases
      of MASS were observed within a patient age range of 71-90 years, whereas only 14
      cases (19%) were observed within an age range of 41-60 years. Pre-enucleation
      radiation significantly reduced the incidence of MASS. Twenty-two (10%) of the
      total 218 eyes had received pre-enucleation radiation and in only two (1%) of
      these was MASS observed. Melanoma associated spongiform scleropathy was found
      only in areas of contact between the tumour and the sclera, and the degree of
      MASS correlated directly with the extent of this contact. No significant
      correlation with tumour cell type was found. CONCLUSIONS: In eyes with MASS, the
      severity of the changes correlated to the extent of direct contact between the
      tumour and sclera. Melanoma associated spongiform scleropathy showed a
      significant predilection towards older age groups. Pre-enucleation radiation
      significantly reduced the incidence of MASS. Melanoma associated spongiform
      scleropathy is probably caused by a deposition of amorphous material splitting
      the scleral collagen fibrils. This material may be secreted either directly from
      the adjacent tumour or from scleral fibroblasts stimulated by the tumour cells.

PMID- 12059875
TI  - Effects of sympathetic denervation on the hyaluronan content of the anterior
      segment in the normal and traumatized rabbit eye.
AB  - PURPOSE: To determine whether there is any involvement of sympathetic nerves in
      the regulation of ocular hyaluronan production in the normal and traumatized
      rabbit iris. METHODS: Unilateral sympathetic denervation was performed by
      removing the right superior cervical ganglion. Hyaluronan concentrations in the
      iris and aqueous were measured with a radiometric assay at various time intervals
      after denervation. Peripheral iridectomy was also performed in both denervated
      and non-denervated eyes. RESULTS: Hyaluronan concentrations in the iris tissue
      after denervation were observed to have increased after 1 day, reaching a peak of
      129.6 +/- 5.7 microg/g wet weight at day 3. Two weeks later, hyaluronan
      concentrations had fallen back to normal levels. Ocular trauma with peripheral
      iridectomy in denervated eyes caused an increase of hyaluronan content of up to
      253.5 +/- 30.5 microg/g wet weight, which was not significantly different from
      hyaluronan concentrations observed after the same trauma in non-denervated eyes.
      CONCLUSION: Cervical sympathetic denervation results in a moderate increase of
      the hyaluronan content in the rabbit iris and does not appear to influence the
      hyaluronan response of the iris to trauma.

PMID- 12059876
TI  - Accidental mydriasis from exposure to Angel's trumpet (Datura suaveolens).
AB  - PURPOSE: To report clinical findings after accidental instillation into the eye
      of sap from Angel's trumpet (Datura suaveolens). METHODS: We report findings on
      seven patients who developed sudden onset of unilateral mydriasis. At least three
      of them also had ipsilateral cycloplegia and one developed transient tachycardia.
      RESULTS: The symptoms evolved after ocular exposure to sap from Angel's trumpet,
      a plant containing natural alkaloids with parasympatholytic properties. Six
      patients were initially unaware of the cause of their symptoms. In these cases,
      patient history revealed recent contact with Angel's trumpet. CONCLUSION:
      Accidental ocular instillation of sap from Angel's trumpet should be noted as a
      cause of sudden onset of mydriasis in otherwise unaffected patients and also of
      general symptoms like tachycardia.

PMID- 12059877
TI  - Orbital intramuscular haemangioma.
AB  - PURPOSE: To present the clinical and histopathological characteristics of an
      intramuscular haemangioma in the extraocular muscles. METHODS: In 1989, an
      otherwise healthy 21-year-old female developed proptosis of the left eye.
      Clinical examination revealed a painless, non-compressible, retrobulbar lesion.
      No discoloration of skin or conjunctiva could be observed. The patient had no
      history of head injury. She underwent surgery three times over a period of 9
      years, without reaching a diagnosis. The tumour increased slowly in size despite
      the operations and MR imaging suggested a tumour of angiomatous origin. Finally,
      radical surgery was performed with enucleation of the left eye and excision of
      affected extraocular muscles. RESULTS: Histopathological examination of the
      removed orbital tumour showed a mixed type intramuscular haemangioma involving
      four extraocular muscles. CONCLUSION: We report the first case of an
      intramuscular haemangioma of the orbit.

PMID- 12059878
TI  - Ocular ochronosis: A case report and clinical findings.
AB  - PURPOSE: To report a rare case of bilateral asymmetrical melanin-like pigments
      found in the cornea, conjunctiva and sclera. METHODS: Systemic investigation with
      clinical and laboratory analysis. RESULTS: The case was diagnosed as one of
      alkaptonuria and ocular ochronosis.

PMID- 12059879
TI  - Effects of antiepileptic drugs on visual function, with special reference to
      Vigabatrin.

PMID- 12059880
TI  - Acute infectious mononucleosis presenting with dacryoadenitis and tonsillitis.

PMID- 12059884
TI  - Small-volume resuscitation: from experimental evidence to clinical routine.
      Advantages and disadvantages of hypertonic solutions.
AB  - BACKGROUND: The concept of small-volume resuscitation (SVR) using hypertonic
      solutions encompasses the rapid infusion of a small dose (4 ml per kg body
      weight, i.e. approximately 250 ml in an adult patient) of 7.2-7.5% NaCl/colloid
      solution. Originally, SVR was aimed for initial therapy of severe hypovolemia and
      shock associated with trauma. METHODS: The present review focuses on the findings
      concerning the working mechanisms responsible for the rapid onset of the
      circulatory effect, the impact of the colloid component on microcirculatory
      resuscitation, and describes the indications for its application in the
      preclinical scenario as well as perioperatively and in intensive care medicine.
      RESULTS: With respect to the actual data base of clinical trials SVR seems to be
      superior to conventional volume therapy with regard to faster normalization of
      microvascular perfusion during shock phases and early resumption of organ
      function. Particularly patients with head trauma in association with systemic
      hypotension appear to benefit. Besides, potential indications for this concept
      include cardiac and cardiovascular surgery (attenuation of reperfusion injury
      during declamping phase) and burn injury. The review also describes disadvantages
      and potential adverse effects of SVR: CONCLUSION: Small-volume resuscitation by
      means of hypertonic NaCl/colloid solutions stands for one of the most innovative
      concepts for primary resuscitation from trauma and shock established in the past
      decade. Today the spectrum of potential indications involves not only prehospital
      trauma care, but also perioperative and intensive care therapy.

PMID- 12059885
TI  - Post spinal meningitis and asepsis.
AB  - BACKGROUND: Post spinal meningitis (PSM) is a complication still currently being
      reported. After two PSM cases in our hospital an epidemiological study was
      initiated, which included a survey of techniques for asepsis that are applied in
      our department. METHODS: Cases defined as PSM comprised meningitis within a week
      after spinal anesthesia. Anesthesia records, anesthesia complication files and
      the records of the Hospital Commission for Infection Control from 1997 to 2000
      were reviewed. Asepsis techniques applied were surveyed by a questionnaire
      answered by all our department's anesthesiologists. The equipment and procedures
      for spinal anesthesia were listed. Current anesthesia textbooks were reviewed for
      recommendations regarding asepsis techniques in conjunction with spinal
      anesthesia. RESULTS: Three cases of PSM were identified following 38,128 spinal
      anesthesias whereas none was observed in 12,822 patients subjected to other types
      of regional or general anesthesia (P>0.05). Culture of cerebrospinal fluid
      yielded Streptococcus in two patients and was negative in the other patient. The
      asepsis technique applied by the anesthesiologists varied considerably. The
      literature review showed that aspects on asepsis for spinal anesthesia are poorly
      covered. CONCLUSION: The incidence of meningitis was similar in patients
      subjected to spinal anesthesia and in those subjected to other anesthetic
      techniques. Asepsis techniques were found to differ considerably among our staff
      members, reflecting the lack of well-defined published standards for this
      procedure. We recommend that asepsis for spinal anesthesia should not be less
      rigorous than for surgical asepsis.

PMID- 12059886
TI  - Comparison of epidural pain treatment with sufentanil-ropivacaine infusion with
      and without epinephrine in children.
AB  - BACKGROUND: Epidural analgesia provides outstanding pain relief after surgery,
      but it is also associated with numerous adverse effects. In order to improve
      postoperative pain management in children we determined whether the use of
      epinephrine added to epidural sufentanil-ropivacaine infusion reduced drug
      requirements, the intensity and duration of postoperative pain and the incidence
      and severity of adverse effects. METHODS: A prospective, randomized, double
      blind, parallel group study design was used in 61 children. The children were
      given continuous epidural sufentanil-ropivacaine infusion either with (n=32) or
      without (n=29) epinephrine for postoperative analgesia. Intravenous ketoprofen, a
      non-steroid anti-inflammatory drug, was used for all children, and epidural
      ropivacaine was used for rescue analgesia. The drug consumption, intensity of
      pain at rest and during activity, and all adverse effects were recorded. RESULTS:
      : The need for sufentanil (P=0.001) and ropivacaine (P=0.006) was significantly
      lower in the with-epinephrine group than in the without-epinephrine group. The
      mean duration of epidural infusion (62 h) was similar in both groups. Four
      children in the without-epinephrine group were noticed to have a low oxygen
      saturation (SpO2<90%), and in one child a low respiratory rate (8 breaths min-1).
      The incidence of pruritus was higher in the without-epinephrine group (P=0.026).
      CONCLUSION: Both infusions provided effective pain relief, and epinephrine as an
      adjuvant to continuous epidural sufentanil-ropivacaine infusion seems to be
      useful in children.

PMID- 12059887
TI  - Retrospective evaluation of continuous epidural infusion for postoperative pain
      in children.
AB  - BACKGROUND: The safety and efficacy of postoperative epidural analgesia (EDA) in
      children are not well documented in larger series of patients given routine
      postoperative care. The aims of this study were to evaluate the efficacy of pain
      relief, determine the incidence and type of complications during the entire
      period of epidural pain treatment in children, and assess the factors affecting
      efficacy METHODS: Children treated postoperatively with an EDA infusion during
      the period 18 September 1994 to 1 January 1999 were studied. Data regarding the
      age, gender, efficacy of analgesia, duration of epidural infusion, types of side
      effects and complications, reasons for discontinuation, and types and duration of
      surgery were collected daily by the Acute Pain Treatment Service. The sensory
      dermatomal level of the surgical incision site was included retrospectively.
      RESULTS: Five hundred and eighteen epidural infusions were given to 476 children.
      Pain relief was rated as 'good' at 76% of visits. There were no major
      complications or sequelae. Thirty-seven per cent of the epidural infusions were
      prematurely discontinued, and 21% were discontinued because of unsatisfactory
      analgesia. Factors related to a higher percentage of unsatisfactory function were
      surgical incision site located above the umbilicus, gastroenterologic surgery,
      protracted surgery and age. Age and duration of surgery were significantly
      related to unsatisfactory function. CONCLUSION: This study shows that continuous
      epidural infusion for postoperative pain was satisfactory in most cases, and that
      no major side-effects or complications occurred in children nursed on regular
      wards. The early recognition of unsatisfactory function of an EDA is important
      for a child's well being.

PMID- 12059888
TI  - Epidural buprenorphine in management of pain in multiple rib fractures.
AB  - BACKGROUND: Pain from multiple rib fractures may affect pulmonary function,
      morbidity, and length of stay in the intensive care units. This study describes
      some clinical characteristics of epidural buprenorphine, a lipophilic and partial
      opiate agonist with a higher micro receptor affinity than morphine, in combating
      the pain in multiple rib fractures. METHODS: The study was conducted
      prospectively over a 15-month period. A total of 27 patients admitted to the
      hospital with multiple rib fractures were studied. Buprenorphine at a
      concentration of 0.3 mg in 5-10 ml normal saline was administered epidurally,
      twice daily the first 24 h, thereafter once daily. Ventilatory function tests
      (including vital capacity, tidal volume, respiratory rate, and minute volume) and
      assessment of pain intensity using a simple, categorical, verbal rating scale
      were obtained before and after institution of analgesia. Any nausea, vomiting,
      hypotension, urinary retention, respiratory depression or pruritus were recorded.
      RESULTS: We found a significant improvement in ventilatory function tests during
      the 1st, 2nd, and 3rd day after epidural analgesia when compared with the
      preanalgesia levels (P < 0.001). Changes in the verbal rating scale demonstrated
      that epidural buprenorphine was associated with marked improvement in pain at
      rest and pain during coughing and deep breathing. None of our patients developed
      hypotension (<10% of the baseline), urinary retention or respiratory depression.
      Nausea, vomiting, and mild pruritus were the only reported complications.
      CONCLUSIONS: Epidurally introduced narcotic, like buprenorphine in saline, has
      been found to be effective in our study to achieve adequate analgesia in
      treatment of patients with multiple rib fractures. In addition, this methodology
      of pain relief eliminates the costly delivery system and early discharge, and
      allows walking epidurals and follow-up on outpatient basis.

PMID- 12059889
TI  - Electrophysiologic cardiac effects of the new local anesthetic IQB-9302 and of
      bupivacaine in the anesthetised dog.
AB  - BACKGROUND: Local anesthetics are not free from potentially fatal complications.
      Therefore every new local anesthetic should be tested to demonstrate a lower, or
      at least similar, degree of toxicity over clinically used analogs. Most toxic
      effects from local anesthetics affect the cardiac electrophysiologic function, so
      the aim of this study was to characterize the electrophysiologic effects of a new
      long-acting local anesthetic (IQB-9302, Ciprocaine), and compare them with those
      of bupivacaine in the anesthetized dog. METHODS: Eight Beagle dogs received three
      increasing infusion doses of either IQB-9302 or bupivacaine. Under isoflurane
      anesthesia, dogs were instrumented to monitor cardiovascular (cardiac output,
      arterial and venous blood pressures) and cardiac electrophysiologic data (sinus
      and atrioventricular (AV) node function, atrial, nodal and ventricular conduction
      times, and refractoriness). RESULTS: Only the highest dose of both drugs induced
      hemodynamic or electrophysiologic alterations: cardiac output and heart rate were
      reduced while blood pressures remained unchanged. Atrial and intranodal
      conduction times and atrial refractoriness increased similarly with both
      anesthetics, but to a slightly lesser extent with IQB-9302. Significant increases
      in His-Purkinje and intraventricular conduction times were the most severe
      noxious effects and occurred only with large doses of either drug. IQB-9302 was
      slightly less toxic than bupivacaine and, unlike this latter drug, potentially
      fatal arrhythmias were not induced. CONCLUSION: IQB-9302 has hemodynamic and
      cardiac electrophysiologic effects similar to those caused by bupivacaine.
      Nevertheless, slightly less toxic effects were derived from IQB-9302
      administration than with bupivacaine, and, unlike the latter, the former might be
      less proarrhytmogenic. The new long-acting local anesthetic IQB-9302 may offer
      clinical advantages compared with bupivacaine.

PMID- 12059890
TI  - Improved long-lasting postoperative analgesia, recovery function and patient
      satisfaction after inguinal hernia repair with inguinal field block compared with
      general anesthesia.
AB  - BACKGROUND: Inguinal hernia repair is a common surgical procedure, and different
      types of anesthetic techniques are in use. We wanted to test if preoperative
      inguinal field block (IFB) with ropivacaine would provide benefits in the
      postoperative period compared with general anesthesia and wound infiltration.
      METHODS: Sixty patients scheduled for inguinal hernia repair were randomized to
      receive general anesthesia with wound infiltration postoperatively, or inguinal
      field block (IFB) before surgery, with no or only light sedation
      intraoperatively. General anesthesia was induced with midazolam, fentanyl and
      propofol, maintained with propofol and alfentanil, and supplemented with nitrous
      oxide in oxygen through a laryngeal mask. The IFB was performed by an
      anesthesiologist, with 50-60 ml ropivacaine and 5 mg/ml with a dedicated
      technique. RESULTS: All significant differences were in favor of the IFB group:
      less pain (visual analog scale, verbal pain score) postoperatively and until day
      7, faster mobilization with less pain, lower analgesic consumption, and higher
      patient satisfaction. CONCLUSION: Preoperative inguinal field block for hernia
      repair provides benefits for patients in terms of faster recovery, less pain,
      better mobilization and higher satisfaction throughout the whole first
      postoperative week.

PMID- 12059891
TI  - Plasma cholinesterase activity and duration of action of mivacurium in
      phenotypically normal patients.
AB  - BACKGROUND: The short duration of action of mivacurium is due to its rapid
      hydrolysis by plasma cholinesterase (pChe). In patients with normal phenotype,
      low pChe activity because of, for instance, disease or intake of drugs may
      prolong the duration of action of mivacurium. The purpose of this study was to
      evaluate the relationship between pChe activity and the duration of action of
      mivacurium 0.2 mg/kg in phenotypically normal patients. MATERIAL: Forty-three
      adult patients with normal pChe phenotype and low or normal pChe activity,
      undergoing a variety of surgical procedures were included in the study with their
      informed consent and Ethics Committee approval. The neuromuscular block was
      monitored using TOF stimulation every 12 s and mechanomyography. The time to
      reappearance of the first response to TOF stimulation was measured. RESULTS: The
      patients pChe activities ranged from 45 to 1272 U/l (normal range 660-1620 U/l)
      and the time to first response to TOF from 8.1 to 62.7 min. An inverse
      relationship between enzyme activity and duration of action of mivacurium was
      found. The relationship was described by the equation: log10 (time) =alpha- beta
      log10 (pChe), where alpha (SD) is 2.547 (0.186) and beta (SD) 0.454 (0.069).
      CONCLUSION: In patients with phenotypically normal pChe, prediction of the
      duration of action of mivacurium is possible from the patients actual pChe
      activity. In patients with pChe activities below the normal range, the time to
      reappearance of the first response to TOF stimulation may vary from 10 to 180 min
      Only patients with pChe activities <220 U/l had a significantly prolonged
      duration of action of mivacurium.

PMID- 12059892
TI  - Pharmacokinetics and pharmacodynamics of mivacurium in young adult and elderly
      patients.
AB  - BACKGROUND: Mivacurium is hydrolyzed by plasma cholinesterase, and is therefore
      less dependent on liver metabolism and renal elimination than other neuromuscular
      blocking drugs. This might favor the use of mivacurium in elderly patients. The
      purpose of this study was to compare the pharmacodynamics and the
      pharmacokinetics of the three isomers of mivacurium and their metabolites in
      young adult and elderly patients. METHODS: Sixty-four patients were included in a
      dose-response study, in which 32 young adults and 32 elderly patients received
      one of four doses of mivacurium. An additional bolus dose of mivacurium to a
      total of 0.1 mg/kg was given followed by a continuous infusion adjusted to
      maintain a 91-99% neuromuscular block. The times to maximum block and different
      levels of recovery were measured using mechanomyography and train-of-four (TOF)
      nerve stimulation. Thirty-two patients were randomly selected for the
      pharmacokinetic study. Venous samples were taken for determination of the three
      mivacurium isomers and the metabolites. RESULTS: The estimated ED95 were 0.053
      and 0.061 mg/kg in young adults and elderly patients, respectively (NS). The
      median infusion rate did not differ, but duration to a TOF ratio of 0.7 was
      significantly longer in elderly patients than in young adult patients (21.0 vs.
      16.5 min). No statistically significant difference between the age groups in
      clearance and elimination half-life of the isomers was seen. The half-lives of
      the metabolites were significantly prolonged in the elderly patients. CONCLUSION:
      There were no significant differences in the potency or infusion requirements
      between the adult and elderly patients, but the rate of recovery was
      significantly, though only moderately prolonged, in the elderly patients. No
      significant difference in clearance was seen but the elimination half-lives of
      the metabolites was longer in the elderly patients.

PMID- 12059893
TI  - Mutation screening in the ryanodine receptor 1 gene (RYR1) in patients
      susceptible to malignant hyperthermia who show definite IVCT results:
      identification of three novel mutations.
AB  - BACKGROUND: The ryanodine receptor of the skeletal muscle (RYR1) seems to be of
      outstanding importance in the pathogenesis of malignant hyperthermia (MH). It has
      been shown that point mutations in the RYR1 gene are strongly associated with the
      MH phenotype. A correctly determined phenotype is the basic prerequisite for
      adequate genetic MH screening. In this study we examined only those MH
      susceptible patients for the presence of potential RYR1 mutations who showed
      strong pathological muscle responses in the in vitro contracture test (IVCT).
      METHODS: A total of 56 MHS index patients who complied with the following IVCT
      criteria were included in the molecular genetic investigation: Contracture forces
      > or =4 mN at a caffeine concentration of 2.0 mmol/l and > or =8 mN at a
      halothane concentration of 0.44 mmol/l. DNA sequences of exons 2, 6, 9, 11, 12,
      14, 15, 17, 39, 40, 45, 46, 102 of the RYR1 gene were analysed by the direct
      sequencing technique. Furthermore, if an MH mutation was identified in an index
      patient, all relatives were screened for their family specific RYR1 defect.
      RESULTS: In 39 index patients an RYR1 mutation was detected: Arg163Cys (n = 2),
      Asp166Asn (n = 1), Gly341Arg (n = 2), Arg401His (n = 2), Arg614Cys (n = 12),
      Asp2129Glu (n = 1),Vol2168Met (n = 1), Thr2206Met (n = 9), Ala2428Thr (n = 1),
      Gly2434Arg (n = 2), Arg2435His (n = 1), Arg2452Trp (n = 1), Arg2454His (n = 4).
      Three new RYR1 mutations were identified. We found a potential MH mutation in a
      further 130 relatives of the 39 index patients. Thirty-seven individuals were
      classified as MHS exclusively by molecular genetic techniques and did not have to
      undergo the IVCT. CONCLUSIONS: The ascertained high rate of successful MH
      mutation screening (69.64%) is obviously associated with the more clearly defined
      MHS diagnosis in the IVCT. According to the EMHG guidelines for the molecular
      genetic detection of MH susceptibility, a positive MH disposition could be
      determined in numerous persons by a less invasive technique.

PMID- 12059894
TI  - Comparative effects of xenon and nitrous oxide on diaphragmatic contractility in
      dogs.
AB  - BACKGROUND: Xenon at two different concentrations (30%, 60%) has no effect on
      diaphragmatic contractility. This study was undertaken to compare the effects of
      xenon and nitrous oxide (N2O), a commonly used and well-established gas
      anesthetic, on diaphragmatic contractility in dogs. METHODS: Twenty-one
      pentobarbitone-anesthetized dogs were randomly divided into three groups of seven
      each: group 1 received xenon 30% (0.25 MAC) in oxygen; group 2 received N2O 47%
      (0.25 MAC) in oxygen; and group 3 received N2O 60% (0.32 MAC) in oxygen.
      Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at
      low- (20-Hz) and high-frequency (100-Hz) stimulation, after maintaining 60 min of
      stable condition. The integrated electrical activity of diaphragm (Edi) to each
      stimulus was measured. RESULTS: With an inhalation of xenon 30%, N2O 47%, or N2O
      60%, Pdi and Edi at both stimuli did not change. No difference in Pdi or Edi was
      observed among the groups. CONCLUSION: When used at clinical concentration, xenon
      or N2O does not affect contractility and electrical activity of the diaphragm in
      dogs.

PMID- 12059896
TI  - Myocardial tissue oxygen during coronary artery constriction and hypotension in
      dogs.
AB  - BACKGROUND: Sodium nitroprusside (SNP) may decrease myocardial tissue oxygenation
      in dogs with normal coronary arteries. We compared SNP- with desflurane-induced
      hypotension on myocardial tissue oxygen and pH in dogs with left anterior
      descending artery constriction. METHODS: Twenty-four dogs were anesthetized with
      8% desflurane for baseline anesthesia. Catheters were inserted into the femoral
      artery and vein and the coronary sinus. A flow probe and flow restriction device
      was placed on the left anterior descending (LAD) artery. A probe that measured
      myocardial oxygen pressure was inserted into the middle myocardium in the LAD
      region. Baseline measures were made of LAD artery flow, arterial and coronary
      sinus blood gases, and myocardial tissue gases. A 30% decrease in blood pressure
      was induced with SNP with unrestricted LAD flow (n=6) or when LAD artery flow was
      restricted by 30% from baseline (n=6). In separate dogs, a 30% decrease in blood
      pressure was produced with 14 +/- 1% desflurane with unrestricted LAD flow (n=6)
      or with baseline LAD artery flow restricted by 30% (n=6). RESULTS: During SNP
      induced hypotension with no LAD constriction, LAD artery flow and coronary sinus
      oxygen tension increased but myocardial tissue oxygen tension (PmO2) decreased by
      40%. When baseline artery flow was decreased by 30% by LAD constriction, SNP
      induced hypotension decreased tissue oxygen pressure by 80%, and ischemic
      acidosis was produced. During unrestricted LAD artery flow or with a 30% flow
      restriction, desflurane-induced hypotension produced no significant change from
      baseline myocardial tissue oxygen tension or pH. CONCLUSION: During coronary
      artery constriction, desflurane-induced hypotension maintained myocardial tissue
      oxygenation and pH better than did SNP-induced hypotension. The divergence
      between tissue and coronary sinus oxygen tension during SNP suggests that
      arteriovenous shunting may occur.

PMID- 12059895
TI  - Intraocular pressure more reduced during anesthesia with propofol than with
      sevoflurane: both combined with remifentanil.
AB  - BACKGROUND: Short-acting anesthetic agents are suitable and commonly used in
      ocular surgery. Propofol and remifentanil are known to reduce intraocular
      pressure (IOP), but no information is available regarding the effects of
      sevoflurane combined with remifentanil on IOP. METHODS: Therefore, a prospective,
      randomized study was conducted to compare the effects on IOP of two different
      anesthetic techniques: one based on a total intravenous anesthesia with propofol
      (Group P, bolus 1.5-2.0 mg/kg, maintenance 3.0-7.0 mg/kg/h); and the other based
      on sevoflurane (Group S, inhalational induction, end-tidal concentration 0.7-1.2
      vol.%). An infusion of remifentanil (10 microg/kg/h) was used with both
      techniques. In ASA I-III patients with normal IOP undergoing elective cataract
      surgery, using an applanation tonometer, IOP was measured contralateral to the
      operated eye at nine predefined time points before, during and after anesthesia.
      RESULTS: The two groups (n=20 each) were comparable with regard to demographic
      data and hemodynamic variables. Baseline IOP was 14.2+/-2.8 mmHg (Group P) and
      14.1+/-2.4 mmHg (Group S; NS). During and following the induction of anesthesia,
      IOP was reduced in both groups. Intraocular pressure was significantly lower in
      Group P (6.0+/-3.2 mmHg) than in Group S (8.9+/-3.4 mmHg) during the induction of
      anesthesia. CONCLUSION: In patients undergoing cataract surgery under general
      anesthesia with tracheal intubation, anesthetic regimens with propofol as well as
      with sevoflurane, both combined with remifentanil, decrease IOP significantly.
      The decrease in IOP was significantly more pronounced in the propofol group than
      in the sevoflurane group.

PMID- 12059897
TI  - Hepatic function during xenon anesthesia in pigs.
AB  - BACKGROUND: Inhalation anesthetics decrease liver perfusion and oxygen
      consumption by changing the distribution pattern of perfusion between the hepatic
      artery and the portal vein and by direct effects on liver cells. The effects of
      xenon on liver perfusion and function have been not investigated until now.
      METHODS: Fourteen pigs were randomly assigned to two groups to receive either 73
      78% xenon or 75% nitrogen in oxygen with additional supplementation of
      pentobarbital and buprenorphine. Microspheres were used to determine the arterial
      perfusion of the liver and splanchnic organs. Oxygen contents were measured by
      catheterization of the portal and a liver vein. Lactate and glucose plasma
      concentrations were measured in hepatic, mixed venous and arterial blood. Alanine
      aminotransferase (ALT) and lactate dehydrogenase (LOH) plasma concentrations were
      measured in arterial blood. Urea production rates were calculated to assess
      hepatic metabolic function. RESULTS: Significant higher oxygen contents were
      found in the liver venous blood during xenon anesthesia. No differences were
      found in any other investigated parameters. CONCLUSION: Higher oxygen content in
      liver venous blood observed during xenon anesthesia was not induced by changes in
      hepatic perfusion distribution or by an impairment of liver metabolic capacity.
      However, it can be explained by similar results known from inhalation anesthesia.
      Additionally, the effect can be caused by the reduction of plasma catecholamine
      concentrations during xenon anesthesia.

PMID- 12059898
TI  - Effects of lung recruitment maneuver and positive end-expiratory pressure on lung
      volume, respiratory mechanics and alveolar gas mixing in patients ventilated
      after cardiac surgery.
AB  - BACKGROUND: It is unclear whether positive end-expiratory pressure (PEEP) is
      needed to maintain the improved oxygenation and lung volume achieved after a lung
      recruitment maneuver in patients ventilated after cardiac surgery performed in
      the cardiopulmonary bypass (CPB). METHODS: A prospective, randomized, controlled
      study in a university hospital intensive care unit. Sixteen patients who had
      undergone cardiac surgery in CPB were studied during the recovery phase while
      still being mechanically ventilated with an inspired fraction of oxygen (FiO2)
      1.0. Eight patients were randomized to lung recruitment (two 20-s inflations to
      45 cmH2O), after which PEEP was set and kept for 2.5 h at 1 cmH2O above the
      pressure at the lower inflexion point (14+/-3 cmH2O, mean +/-SD) obtained from a
      static pressure-volume (PV) curve (PEEP group). The remaining eight patients were
      randomized to a recruitment maneuver only (ZEEP group). End-expiratory lung
      volume (EELV), series dead space, ventilation homogeneity, hemodynamics and PaO2
      (oxygenation) were measured every 30 min during a 3-h period. PV curves were
      obtained at baseline, after 2.5 h, and in the PEEP group at 3 h. RESULTS: In the
      ZEEP group all measures were unchanged. In the PEEP group the EELV increased with
      1220+/-254 ml (P<0.001) and PaO2 with 16+/-16 kPa (P<0.05) after lung
      recruitment. When PEEP was discontinued EELV decreased but PaO2 was maintained.
      The PV curve at 2.5 h coincided with the curve obtained at 3 h, and both curves
      were both steeper than and located above the baseline curve. CONCLUSIONS:
      Positive end-expiratory pressure is required after a lung recruitment maneuver in
      patients ventilated with high FiO2 after cardiac surgery to maintain lung volumes
      and the improved oxygenation.

PMID- 12059899
TI  - Intensive care unit syndrome/delirium is associated with anemia, drug therapy and
      duration of ventilation treatment.
AB  - BACKGROUND: We have performed a prospective qualitative investigation of the ICU
      syndrome/delirium; the main parts of which have recently been published. The aim
      of the present study was to explore the relationship between the ICU
      syndrome/delirium and age, gender, length of ventilator treatment, length of stay
      and severity of disease, as well as factors related to arterial oxygenation and
      the amount of drugs used for sedation/analgesia. METHODS: Nineteen mechanically
      ventilated patients who had stayed in the ICU for more than 36 h were closely
      observed during their stay, and interviewed in depth twice after discharge.
      Demographic, administrative and medical data were collected as a part of the
      observation study. RESULTS: Patients with severe delirium had significantly lower
      hemoglobin concentrations than those with moderate or no delirium (P=0.033).
      Patients suffering from severe delirium spent significantly longer time on the
      ventilator and at the ICU, and were treated with significantly higher daily doses
      of both fentanyl (P=0.011) and midazolam (P=0.011) in comparison with those
      reporting only moderate or no symptoms of delirium. There were no significant
      differences in the Therapeutic Intervention Scoring System scores, reflecting the
      degree of illness, between patients with and without delirium. CONCLUSION: The
      development of the ICU syndrome/delirium seems to be associated with decreased
      hemoglobin concentrations and extended times on the ventilator. Prolonged ICU
      stays and treatment with higher doses of sedatives and opioids in patients with
      delirium appear to be secondary phenomena rather than causes.

PMID- 12059900
TI  - Monitoring functional residual capacity (FRC) by quantifying oxygen/carbon
      dioxide fluxes during a short apnea.
AB  - BACKGROUND: Clinically applicable methods for measuring FRC are currently
      lacking. This study presents a new method for FRC monitoring based on
      quantification of metabolic gas fluxes of O2 and CO2 during a short apnea.
      METHODS: Base line exchange of oxygen and carbon dioxide was measured with
      indirect calorimetry. End-tidal ( approximately alveolar) O2 and CO2
      concentrations were measured before and after a short apnea, 8-12 s, and FRC was
      calculated according to standard washin/washout formulas taking into account the
      increased solubility of CO2 in blood when the tension is increased during the
      apnea. The method was tested in a lung model with CO2 excretion and O2
      consumption achieved by combustion of hydrogen and implemented in six ventilator
      treated patients with acute respiratory failure (ARF). RESULTS: In the lung model
      the method showed excellent correlation (r = 0.98) with minimal bias (34 ml) and
      a good precision, limits of agreement being 160 and -230 ml, respectively,
      compared to the reference method. In six ARF patients changes in FRC induced by
      increase or decrease in PEEP and measured with the O2/CO2 flux FRC method
      corresponded well with changes in reference values of FRC (r = 0.76-0.94).
      CONCLUSIONS: A new method has been proposed in which FRC could be monitored from
      measurements of physiological fluxes of gases during a short apnea with the use
      of standard ICU equipment and some calculations. We anticipate that with further
      development, this technique could provide a new tool for monitoring respiratory
      changes and ventilator management in the ICU.

PMID- 12059901
TI  - Malignant bladder tumor transurethral resection in a patient with acquired C1
      inhibitor deficiency.
AB  - Acquired C1-INH deficiency or acquired angiodema (AAE) is an uncommon cause of
      angiedema that can induce severe airway complications during surgical procedures.
      We present the perioperative management of a patient with AAE secondary to a
      malignant bladder tumor. Anesthetic guidelines could be useful in the management
      of this disorder.

PMID- 12059902
TI  - Resistance to vecuronium in a term neonate.
AB  - We report a case of resistance to curarization in a term neonate undergoing
      surgery. The dosage of vecuronium required to obtain satisfactory muscular
      blockade and cessation of spontaneous breathing efforts was more than 10-fold the
      normal one. The operation was delayed for 90 min The mechanism of this marked
      resistance is unknown, but some possible hypotheses are presented, focusing on
      the neonate's poor intrauterine growth and an abnormality in pharmacodynamics.

PMID- 12059903
TI  - Epidural blood patch for treatment of spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension is an uncommon disease caused by
      cerebrospinal fluid leakage. We reported a case of a 42-year-old male with
      postural headache who was diagnosed as having spontaneous intracranial
      hypotension. His headache did not completely improve by conservative therapies,
      so he underwent an autologous epidural blood patch. The site of cerebrospinal
      fluid restoration was identified at the level from the C2 to Th7 epidural space
      by 111In-DPTA cisternography and computed tomography coupled with myelography,
      and cervical EBP was performed. Because cerebrospinal fluid drops from the
      catheter, it is useful to identify the location of the catheter tip under
      contrast injection X-ray. Rapid and dramatic relief from the headache was
      obtained, and no serious complications occurred.

PMID- 12059904
TI  - Anterior ischemic optic neuropathy after emergency caesarean section under
      epidural anesthesia.
AB  - We report a case of non arteritic anterior ischemic optic neuropathy following
      caesarean delivery in a patient who had epidural analgesia. There was doubt as to
      whether it was subdural. The patient underwent caesarean section because of
      second stage non-progression of labor. We discuss the possible etiology of this
      unpleasant complication.

PMID- 12059905
TI  - Repeat cesarean section in a morbidly obese parturient: a new anesthetic option.
AB  - Combined spinal epidural anesthesia (CSEA) has become an increasingly popular
      anesthetic technique for repeat cesarean section. However, the advantages of this
      technique have not routinely been available to morbidly obese patients because of
      the lack of an appropriately long needle. We present a case of a morbidly obese
      parturient who underwent repeat cesarean section under CSEA conducted with the
      recently introduced (and commercially available) CSEA needle set, specifically
      designed for morbidly obese patients.

PMID- 12059906
TI  - Heterogeneity in the granulomatous response to mycobacterial infection in
      patients with defined genetic mutations in the interleukin 12-dependent
      interferon-gamma production pathway.
AB  - Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway
      exhibit a selective susceptibility to severe infections with poorly pathogenic
      mycobacteria and non-typhi salmonella spp. These experiments of nature
      demonstrate that IL-12-dependent IFNgamma production is critical for granuloma
      formation and therefore host immunity against such pathogens. The essential role
      of granuloma formation for protective immunity to these organisms is emphasized
      by the differing granuloma forming capabilities and resultant clinical sequelae
      observed in these patients which seems to reflect their ability to produce or
      respond to IFNgamma (Fig. 9). At one pole of this spectrum, represented by the
      complete IFNgammaR1/2 deficient patients, there is a complete absence of mature
      granuloma formation, whereas with the less severe mutations (i.e. partial
      IFNgammaR1/2, complete IL-12p40 and complete IL-12Rbeta1 deficiency), granuloma
      formation is very heterogenous with wide variations in composition being
      observed. This suggests that in the latter individuals, who produce partial but
      suboptimal IFNgamma responses, other influences, including pathogen virulence and
      host genotype may also affect the type and scale of the cellular response
      elicited.

PMID- 12059909
TI  - Delayed toxicity of cyclophosphamide on the bladder of DBA/2 and C57BL/6 female
      mouse.
AB  - The present study describes the delayed development of a severe bladder pathology
      in a susceptible strain of mice (DBA/2) but not in a resistant strain (C57BL/6)
      when both were treated with a single 300 mg/kg dose of cyclophosphamide (CY).
      Inbred DBA/2 and C57BL/6 female mice were injected with CY, and the effect of the
      drug on the bladder was assessed during 100 days by light microscopy using
      different staining procedures, and after 30 days by conventional electron
      microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both
      strains that was completely repaired in about 7-10 days. After 30 days of CY
      injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of
      DBA/2 mice but only in 4% of C57BL/6 mice. Delayed cystitis was characterized by
      infiltration and transepithelial passage into the lumen of inflammatory cells and
      by frequent exfoliation of the urothelium. Mast cells appeared in the connective
      and muscular layers of the bladder at a much higher number in DBA/2 mice than in
      C57BL/6 mice or untreated controls. Electron microscopy disclosed the absence of
      the typical discoidal vesicles normally present in the cytoplasm of surface
      cells. Instead, numerous abnormal vesicles containing one or several dark
      granules were observed in the cytoplasm of cells from all the epithelial layers.
      Delayed cystitis still persisted in DBA/2 mice 100 days after treatment. These
      results indicate that delayed toxicity of CY in female DBA/2 mice causes a
      bladder pathology that is not observed in C57BL/6 mice. This pathology resembles
      interstitial cystitis in humans and could perhaps be used as an animal model for
      studies on the disease.

PMID- 12059907
TI  - The biology of the combretastatins as tumour vascular targeting agents.
AB  - The tumour vasculature is an attractive target for therapy. Combretastatin A-4
      (CA-4) and A-1 (CA-1) are tubulin binding agents, structurally related to
      colchicine, which induce vascular-mediated tumour necrosis in animal models. CA-1
      and CA-4 were isolated from the African bush willow, Combretum caffrum, and
      several synthetic analogues are also now available, such as the Aventis Pharma
      compound, AVE8062. More soluble, phosphated, forms of CA-4 (CA-4-P) and CA-1 (CA
      1-P) are commonly used for in vitro and in vivo studies. These are cleaved to the
      natural forms by endogenous phosphatases and are taken up into cells. The lead
      compound, CA-4-P, is currently in clinical trial as a tumour vascular targeting
      agent. In animal models, CA-4-P causes a prolonged and extensive shut-down of
      blood flow in established tumour blood vessels, with much less effect in normal
      tissues. This paper reviews the current understanding of the mechanism of action
      of the combretastatins and their therapeutic potential.

PMID- 12059908
TI  - Alteration in plasma glucose levels in Japanese encephalitis patients.
AB  - A unique factor, human T cell hypoglycaemic factor (hTCHF), has been shown to
      produce hypoglycaemia during the convalescent stage in the plasma of patients
      with Japanese encephalitis virus (JEV) infection. The present study was
      undertaken to investigate the ability of T cells from fresh peripheral blood
      mononuclear cells (PBMC) of such patients to produce hTCHF. The PBMC, as well as
      the individual subpopulations, were cultured for 24 h and the culture
      supernatants (CS) were assayed for hypoglycaemic activity. The activity was
      observed in the CD8+ T cells. The hypoglycaemia in JE-confirmed patients
      coincided with the gradual rise in circulating glucagon level, with no
      significant alterations in insulin, growth hormone and cortisol levels. The hTCHF
      was purified by ion exchange chromatography and the purified protein was observed
      as a approximately 25 kDa band on SDS-PAGE. Secretory hTCHF in the sera of
      patients and T cell CS was present in 88% of convalescent serum samples. We
      conclude that during the convalescent stage of JEV infection, a unique factor,
      hTCHF, is secreted by activated CD8+ T cells from patients and that this is
      responsible for the development of hypoglycaemia.

PMID- 12059911
TI  - Evaluation of smear layer removal by EDTAC and sodium hypochlorite with
      ultrasonic agitation.
AB  - AIM: To evaluate smear layer removal by different irrigating solutions under
      ultrasonic agitation. METHODOLOGY: Twenty recently extracted mandibular incisors
      with a single root canal were divided into four equal groups. Three groups were
      instrumented using the modified double-flared technique, the fourth remained
      unprepared. Each group was irrigated with either distilled water, 1.0% sodium
      hypochlorite alone or associated with 15% EDTAC between each file size. The final
      group was not instrumented but irrigated with 1.0% sodium hypochlorite and 15%
      EDTAC. A size 15 file energised by ultrasound was used with small amplitude
      filing movements against the canal walls in all groups. The teeth were split
      longitudinally and the roots measured to provide three sections of the same size
      (cervical, middle and apical). Samples were examined under the scanning electron
      microscope and assessed for the amount of smear layer by three independent and
      calibrated examiners. The scoring system ranged from 1 (no smear layer) to 4 (all
      areas covered by smear layer). Due to the non-parametric nature of the data,
      Friedman's test was used for statistical analysis. RESULTS: Canal walls were
      covered with smear layer in the group irrigated with 1% sodium hypochlorite alone
      and the group irrigated with distilled water. Canals irrigated with 1.0% sodium
      hypochlorite associated with 15% EDTAC had less smear layer throughout the canal
      (P < 0.001). There were no statistical differences for the amount of smear layer
      found on the cervical, middle and apical thirds when each group was analysed
      separately. CONCLUSIONS: Under ultrasonic agitation, sodium hypochlorite
      associated with EDTAC removed the smear layer from root canal walls, whereas
      irrigation with distilled water or 1.0% sodium hypochlorite alone did not remove
      smear layer.

PMID- 12059910
TI  - The induction of reparative dentine by enamel proteins.
AB  - AIM: This study was designed to examine whether enamel matrix derivative (EMD)
      could induce reparative dentine formation without eliciting adverse side-effects
      in pulpotomized teeth in the miniature swine. METHODOLOGY: Pulpotomy was
      performed in 36 mandibular incisor teeth from 11 adult miniature swine. Following
      the surgical procedure, the exposed pulp tissue was treated with EMD or covered
      with a calcium hydroxide preparation (Dycal). Following an observation period of
      3, 4 and 8 weeks, the experimental teeth were extracted and examined using light
      microscopy and histometric analysis. The total amount of reparative dentine
      formed in the EMD-treated teeth was calculated as total area using digital
      histomorphometry analysis of the five central-most sections from each
      experimental tooth. RESULTS: In the EMD-treated teeth, substantial amounts of
      dentine-like tissue formation consistently led to a complete hard-tissue bridging
      of the defects. The onset of hard tissue formation could be observed after 2
      weeks and was located only on the pulpal wound. More limited dentine formation
      was also observed in Dycal-treated teeth. However, in these teeth the new hard
      tissue formed at the expense of pulp chamber width, causing narrowing of root
      canals. The total amount of reparative dentine formed in the EMD-treated teeth
      was significantly higher (P<0.005) than in the Dycal-treated specimens.
      CONCLUSION: These results demonstrate the potential of EMD as a biologically
      active pulp-dressing agent that specifically induces pulpal wound healing and
      dentine formation in the pulpotomized teeth without affecting the normal function
      of the remaining pulp.

PMID- 12059912
TI  - A scanning electron microscopic study of debris and smear layer remaining
      following use of GT rotary instruments.
AB  - AIM: The aim of the present study was to assess debris and smear layer remaining
      following canal preparation with GT rotary instruments. METHODOLOGY: Sixteen
      freshly extracted single-rooted premolar teeth were instrumented with GT rotary
      instruments using a crown-down preparation technique. All specimens were flushed
      with 2 mL of 5% NaOCl between each rotary instrument. At the end of
      instrumentation the following final irrigation sequence was repeated two times: 2
      mL of EDTA + Cetrimide for 1 min (Largal Ultra, Septodont, France) and 2 mL of 5%
      NaOCl for 5 min. A final flush with saline solution was made to halt any chemical
      activity. Two other uninstrumented teeth that were not irrigated served as
      controls. All teeth were split longitudinally and prepared for SEM evaluation.
      The presence of debris and smear layer was evaluated from photomicrographs at
      x200 and x1000 magnification taken in the apical, middle and coronal thirds of
      the canals. Blind evaluation was performed by two trained observers and scores
      were compiled separately. A five category scoring system for debris and smear
      layer was used. Values obtained were tabulated and statistical analysis was
      carried out using a parametric chi-squared test. RESULTS: Statistical analysis
      showed that there was no significant difference between the three regions of the
      root canals (P > 0.05) for debris. Comparison of the removal of the smear layer
      between the three regions showed that there was a statistically significant
      difference between all parts, especially between the coronal and apical thirds (P
      < 0.001). Overall, the coronal sections were cleaner than the middle and apical
      sections. The uninstrumented canals showed walls completely covered with tissue,
      confirming that specimen preparation alone did not remove tissue. CONCLUSIONS:
      Under the conditions of the present study GT rotary instruments removed debris
      effectively, but left root canal walls covered with smear layer, particularly in
      the apical third.

PMID- 12059913
TI  - Bacterial and fungal microleakage of AH26 and AH Plus root canal sealers.
AB  - AIM: To evaluate the penetration of Candida albicans alone and a combination of
      bacteria through root canals filled with gutta-percha and one or other root canal
      sealers, AH26 and AH Plus. METHODOLOGY: Eighty teeth were randomly divided into
      two groups of 40 teeth each and obturated with gutta-percha using either AH26 or
      AH Plus sealer. A further 10 teeth served as negative controls and 10 as positive
      controls. The external surface of each root, except the apical 2 mm, was covered
      with two layers of nail varnish. The teeth were inserted into Eppendorf plastic
      tubes and suspended in glass bottles containing sterile Schaedler broth.
      Streptococcus mutans, Streptococcus mitis, Prevotella melaninogenica and
      Lactobacillus acidophilus were placed in the access cavities of 20 teeth filled
      with AH26 and 20 with AH Plus. Candida albicans was placed in the access cavities
      of the other teeth. The culture medium with microorganisms was changed every 7
      days. Every 72 h bacterial or fungal growth in the broth was tested up to a
      period of 90 days. RESULTS: Leakage in the experimental teeth occurred between 14
      and 87 days. Leakage was present in 47% of all samples. From the samples with
      AH26, 45% leaked bacteria and 60% leaked fungi; whilst from the samples with AH
      Plus, 50% leaked bacteria and 55% fungi. There was no statistically significant
      difference in penetration of bacteria and fungi between the sealers. CONCLUSION:
      In this in vitro study, gutta-percha and the sealers AH26 and AH Plus allowed
      leakage of bacteria and fungi.

PMID- 12059914
TI  - In vitro comparison of different types of sodium perborate used for intracoronal
      bleaching of discoloured teeth.
AB  - AIM: To compare the bleaching efficacy of three different types of sodium
      perborate (SP) commonly used for intracoronal bleaching of discoloured non-vital
      teeth. METHODOLOGY: Sixty-five extracted human maxillary central incisors with
      intact crowns were used. Following obturation with gutta-percha and a root canal
      sealer using a lateral condensation technique, the coronal aspects of the root
      canal fillings were covered with a 1-mm thick protective base placed to a level 1
      mm apical to the labial cemento-enamel junction (CEJ). The teeth were than
      stained artificially with fresh blood over a period of 18 days. One or other of
      the bleaching materials (group 1: SP monohydrate + water, group 2: SP trihydrate
      + water, group 3: SP tetrahydrate + water, group 4: SP monohydrate + hydrogen
      peroxide (HP), group 5: SP trihydrate + HP, group 6: SP tetrahydrate + HP) were
      placed in the pulp chamber of the discoloured teeth and sealed with Cavit for 21
      days. They were replaced with fresh preparations after 3, 7 and 14 days. The
      shades of the tooth crowns were evaluated at baseline and at 7, 14 and 21 days.
      Comparison of tooth shades was completed at each interval and analysed
      statistically using the chi-squared test. RESULTS: There was no statistically
      significant difference between the groups at 7, 14, 21 days. Period of bleaching
      significantly affected the outcome (P < 0.01). No colour changes were noted in
      the control teeth. CONCLUSION: The data obtained from this study demonstrate that
      sodium perborate can be used mixed with water rather than with hydrogen peroxide
      for bleaching discoloured teeth.

PMID- 12059915
TI  - Reduction in intracanal bacteria during root canal preparation with and without
      apical enlargement.
AB  - AIM: To compare in vitro intracanal bacterial reduction using nickel-titanium
      rotary instruments with and without apical enlargement. METHODOLOGY: Thirty-eight
      palatal roots of maxillary molar teeth, with mature apices were subdivided
      according to lengths and then randomly assigned to two experimental and one
      control groups. The roots were sterilized and then reinfected with Enterococcus
      faecalis, which served as a bacteriological marker. All roots in the experimental
      groups were prepared in a step-down sequence with engine-driven GT rotary files
      at 350 rpm. In experimental group A (n = 16) additional apical enlargement to ISO
      size 35 was performed. In group B (n = 16) a serial step-back technique was
      followed with no apical enlargement. This was combined in groups A and B with
      irrigation with NaOCl and EDTA. In the control group (group C, n = 6) irrigation
      only was carried out, with no mechanical preparation. Samples were then taken
      from the root canals to determine the numbers of remaining bacteria. RESULTS: In
      groups A and B, 15 (94%) and 13 (81%) specimens were rendered bacteria-free,
      respectively. In the control group C none of the specimens were bacteria-free.
      There was a significant difference (P < 0.001) in the antibacterial effects of
      experimental and control regimens. There was, however, no significant difference
      (P = 0.276) between the preparation methods used in the experimental groups.
      CONCLUSIONS: There was no significant difference in intracanal bacterial
      reduction when Ni-Ti GT rotary preparation with NaOCl and EDTA irrigation was
      used with or without apical enlargement preparation technique. It may therefore
      not be necessary to remove dentine in the apical part of the root canal when a
      suitable coronal taper is achieved to allow satisfactory irrigation of the root
      canal system with antimicrobial agents.

PMID- 12059916
TI  - Electronic determination of root canal length in primary teeth with and without
      root resorption.
AB  - AIM: To test an electrical device for determining root canal length in primary
      teeth in vitro, and to compare it with the radiographic length measurement.
      METHODOLOGY: Two examiners determined the root canal length of 24 extracted
      maxillary primary incisors (12 with visible root resorption and 12 without) using
      an electrical root canal meter (Tri Auto ZX, Morita, Dietzenbach, Germany). The
      instrument was left in the root canal after the second examination and a
      radiograph was taken. The whole tooth was cleared by immersion in
      methylsalicylate and subsequently photographed. Both radiographs and photographs
      of cleared teeth were measured and compared with the electronic measurements.
      RESULTS: The evaluation of the radiographs showed a mean distance between the
      instrument tips and apices of 0.60 (+/- 0.41) mm; evaluation of the cleared teeth
      showed an equivalent distance of 0.62 (+/- 0.40) mm. The mean distance between
      instrument tip and acceptable working length (determined with the clearing
      method) was 0.26 (+/- 0.24) mm in teeth without resorption and 0.29 (+/- 0.30) mm
      in teeth with resorption. CONCLUSION: The presence of resorption in primary teeth
      did not affect the accuracy of electrical measurement of root canal length in
      vitro. The application of this method in primary teeth should be evaluated
      further.

PMID- 12059917
TI  - Papilla base incision: a new approach to recession-free healing of the
      interdental papilla after endodontic surgery.
AB  - AIM: The purpose of the present study was to describe and evaluate a new incision
      technique: the papilla base incision. METHODOLOGY: Twenty healthy patients
      referred for surgical treatment of persisting apical periodontitis, who were free
      of periodontal disease and had intact interdental papillae were included in the
      study. The preoperative papilla height was recorded by measuring the distance
      between the contact point and the most coronal point of the papilla. The papilla
      base flap, consisting of the papilla base incision and two releasing incisions,
      was used to expose the bone. The papilla base incision consisted of a shallow
      first incision at the base of the papilla and a second incision directed to the
      crestal bone, creating a split thickness flap in the area of the papilla base.
      Further apically a full thickness flap was raised. Following standard root-end
      resection and filling, flap closure was achieved with microsurgical sutures. The
      papilla base incision was sutured with 2-3 interrupted sutures, which were
      removed 3-5 days after the surgery. The experimental sites were evaluated at the
      conclusion of the surgery, at suture removal and after 1 month, and compared to
      the preoperative findings. The healing pattern, complications and postoperative
      recession were recorded. The experimental sites were observed with a x 3
      magnification and graded as to whether a visible scar resulting from the incision
      could be detected. Twenty experimental sites were analysed. RESULTS: Complete
      closure of the wound was achieved in all cases after surgery. Except for four
      patients with delayed healing at suture removal, all other patients displayed
      rapid healing. No noticeable space was created beneath the contact point area.
      The change in distance between the reference point and the most coronal point of
      the papilla comparing the preoperative and the one-month postoperative situation
      was 0.05 +/- 0.39 mm. The probing depth remained within normal limits. One month
      postoperatively, observation of the incision demonstrated: four sites with a
      visible incision line (grade 1), in seven sites the incision defect could be
      partially detected (grade 2) and nine incisions could not be detected (grade 3).
      CONCLUSIONS: In patients with healthy marginal periodontal conditions the papilla
      base incision allows rapid and predictable recession-free healing following
      marginal surgical exposure of the soft tissues. One month postoperatively the
      majority of the incisions were completely or partially invisible. Long-term
      healing will be studied.

PMID- 12059918
TI  - Incompletely fractured teeth associated with diffuse longstanding orofacial pain:
      diagnosis and treatment outcome.
AB  - AIM: To evaluate the diagnostic value of different clinical findings, and analyse
      the symptoms experienced from teeth with incomplete dentinal fractures in
      patients with diffuse orofacial pain. Secondly, to present the outcome of
      different treatment modalities in these patients. METHODOLOGY: Thirty-two
      patients, referred to the teaching clinic at the Faculty of Dentistry, University
      of Bergen, with poorly localized orofacial pain, were finally diagnosed with 46
      incompletely fractured teeth. The distribution and pattern of pain was thoroughly
      recorded for each patient. The final diagnosis, incompletely fractured tooth, was
      obtained after removal of fillings and direct inspection of possible fracture
      lines. RESULTS: Many of the patients had suffered diffuse orofacial pain for more
      than 1 year, and had earlier consulted dental and medical expertise. Direct
      inspection of fracture lines, combined with staining solution and
      transillumination proved to be the best diagnostic tools. The longer the duration
      of pain before the diagnosis of an incompletely fractured tooth was established,
      the more diffuse was the distribution of pain. Endodontic or restorative
      treatment relieved the symptoms in 90% of the patients, whilst persisting
      symptoms in 10% were considered part of an orofacial pain complex of obscure
      aetiology. CONCLUSION: This study shows that the diagnosis of the incompletely
      fractured teeth in patients with longstanding diffuse orofacial pain symptoms are
      time consuming and represent a diagnostic problem. With appropriate endodontic
      and/or restorative treatment, symptoms were relieved in the majority of cases.

PMID- 12059919
TI  - Stainless steel bands in endodontics: effects on cuspal flexure and fracture
      resistance.
AB  - AIMS: This study investigated the effect of stainless steel bands on cuspal
      flexure and fracture resistance of extracted maxillary premolars. METHODOLOGY:
      Twenty extracted maxillary premolars (10 matched pairs) with mesio-occluso-distal
      (MOD) cavities and endodontic access were subjected to occlusal loading tests
      (100 N) using a servo-hydraulic testing machine. Cuspal deflections were measured
      by an extensometer, with and without the band present. Ten teeth (one of each
      pair) then had the band removed, and all teeth were subjected to loading until
      fracture. RESULTS: Mean cuspal flexure of teeth with bands was one-half of
      flexure without bands (P < 0.001). Teeth with bands fractured at higher load than
      their matched pairs with the band removed (P < 0.001), with mean loads at
      fracture of 1282 N and 729 N, respectively. CONCLUSIONS: The study showed that
      stainless steel bands used in endodontics reduce the cuspal flexure of maxillary
      premolars and increase their fracture resistance.

PMID- 12059920
TI  - Radiographic evaluation of cases referred for surgical endodontics.
AB  - AIM: The aim of this study is to test the hypothesis that more patients with
      failed root-canal treatment or other endodontic problems are referred for
      periradicular surgery rather than nonsurgical re-treatment. METHODOLOGY: Three
      sets of 100 periapical radiographs representing typical cases referred for
      surgical treatment were collected in three departments of oral and maxillo-facial
      surgery situated in different parts of the Netherlands. Of these, a total of 278
      radiographs were evaluated to determine whether endodontic surgery was indicated
      or whether the primary endodontic treatment or endodontic re-treatment was a
      realistic option. An oral and maxillo-facial surgeon, an endodontist and a
      general dental practitioner viewed the radiograph independently under standard
      conditions. RESULTS: Overall, orthograde root-canal (re-)treatment was considered
      possible in 63% of the cases. The results differed between the three examiners
      with the oral surgeon reporting that 41% of cases were amenable to conventional
      treatment, for the general dental practitioner and the endodontists the figures
      were 67 and 80%, respectively. CONCLUSIONS: Based on these observations, it is
      concluded that most of the teeth referred for surgical treatment to an oral
      surgeon could be treated by orthograde nonsurgical root-canal treatment.

PMID- 12059921
TI  - Root and canal morphology of Thai maxillary molars.
AB  - AIM: To investigate the root and canal morphology of 268 maxillary permanent
      molars collected from an indigenous Thai population. METHODOLOGY: The cleaned
      teeth were accessed, the pulp dissolved by sodium hypochlorite under
      ultrasonication, and the pulp system injected with Indian ink. The teeth were
      rendered clear by demineralization and immersion in methyl salicylate. The
      following observations were made: (i) number of roots and their morphology; (ii)
      number of root canals per root; (iii) root-canal configuration in each root using
      Vertucci's classification with additional modifications; and (iv) presence and
      location of lateral canals and intercanal communications. RESULTS: All the
      maxillary first and second molars had three separate roots. Only, half (51%) of
      the maxillary third molars had three separate roots; the other half had fused or
      conical roots. The majority of the distobuccal (98.1-100%) and palatal (100%)
      roots had type I canals. Over half of the mesiobuccal roots of first (65%) and
      second (55%) molars had two canals. The most common (44.2%) canal configuration
      in mesiobuccal roots of first molars was type IV (two canals, two foramina). A
      variety of canal types were found in the mesiobuccal roots of second molars.
      Maxillary third molars showed the greatest diversity of canal morphology. There
      was an increase in the prevalence of lateral canals towards the apical part of
      the roots and intercanal communications were present in 16% of each of first,
      second and third Thai maxillary molars. CONCLUSIONS: The mesiobuccal roots of
      Thai maxillary molars possessed a variety of canal system types. Over 50% of the
      first molars had a second mesiobuccal canal. The palatal and distobuccal canals
      mainly had type I canals. Only, a small proportion (7.3-13.3%) of the roots
      exhibited lateral canals which were the most common in the apical third

PMID- 12059922
TI  - A six-canal maxillary first molar: case report.
AB  - AIM: The aim of this case report is to describe an unusual six-canal maxillary
      first molar tooth. CASE REPORT: The maxillary left first molar of a young African
      American male was treated as an emergency at the first visit. At the second
      visit, the five canals (MB1 and 2, Pal1 and 2 and DB) were easily identified at
      high magnification of 16-25 under an operating microscope. The canals were then
      instrumented and filled using the Microseal technique. A careful radiographic
      examination of the final fill indicated that there was a third canal in the
      palatal root as suggested by a slight extrusion of the filling material between
      the two canals. At the third visit, the fillings of the palatal canals were
      removed and the apical 4mm was re-examined. The existence of a third palatal
      canal exiting between the two apices was verified and subsequently instrumented
      and obturated. KEY LEARNING POINTS: It should be assumed that all molar teeth
      have more than the traditionally expected three canals. The location of root
      canals should be identified at high magnification under the microscope. Careful
      radiographic re-examination of the fillings should be done in order to identify
      possibly missed canals.

PMID- 12059931
TI  - A laboratory study of coronal microleakage using four temporary restorative
      materials.
AB  - AIM: The aim of this study was to compare the sealing abilities of Fermin and
      Canseal with the more popular temporary coronal filling materials, Cavit and
      Caviton. METHODOLOGY: Standardized access cavities were prepared in 160 intact
      human permanent molar teeth. They were divided into five groups consisting of 32
      samples. The teeth were restored using one of the temporary filling materials,
      namely: Fermin, Canseal at two powder to liquid ratios, Caviton and Cavit.
      Thermal cycling and/or load cycling were applied on the samples. Assessment of
      microleakage utilized methylene blue dye penetration. Grading of the microleakage
      pattern was from 1 to 3, with 3 providing the best seal. Results were analyzed
      using two-way anova and by Fisher's PLSD post hoc test (P < 0.05). RESULT:
      Microleakage along Fermin, Caviton and Cavit samples did not go beyond Leakage
      Grade 2. Dye penetration into these materials was noted. This was not observed in
      the two groups of Canseal tested. However, the two groups of Canseal exhibited
      total leakage notably after being subjected to thermal cycling. There was a
      statistically significant difference in the microleakage scores obtained between
      the materials and conditions tested (P < 0.0001). CONCLUSION: Fermin was found to
      exhibit the best seal amongst the four materials tested followed by Caviton, and
      Cavit. Thermal cycling influenced the seal of certain types of temporary filling
      materials more than load cycling.

PMID- 12059932
TI  - Prevalence of yeasts in saliva and root canals of teeth associated with apical
      periodontitis.
AB  - AIMS: To determine: (i) the relative prevalence and diversity of yeasts in
      salivary and root canal samples from the same patients; and (ii) the clinical
      factors associated with their presence in saliva and root canals. METHODOLOGY:
      Sixty root canal samples from teeth associated apical periodontitis and the
      corresponding whole unstimulated saliva samples were obtained from 55 patients.
      The medical history including antibiotic therapy and clinical/radiographic data
      on the teeth were recorded. The samples were serially diluted and cultured on
      yeast & fungi-selective sabouraud dextrose agar. Isolates were characterized and
      speciated by the germ tube formation test, hyphal morphology and a commercial
      biochemical test kit (Rapid ID32C(R) system). RESULTS: Twenty-three yeast
      isolates were recovered from 19 saliva samples and eight isolates from six root
      canal samples. Candida albicans (17/23 & 3/8) and Rodotorula mucilaginosa (2/23 &
      4/8) were the most prevalent isolates from saliva and root canal samples. It was
      significantly (13.8 times) more probable that yeasts would be recovered from root
      canals when they were also present in the saliva (P = 0.021). The effect of
      coronal restoration leakage (P = 0.08) and previous root canal treatment (P =
      0.123) were equivocal. The history of antibiotic therapy had no association with
      the presence of yeasts in saliva (OR = 1.1). CONCLUSIONS: Yeasts occurred
      relatively infrequently (10%) in root canals. Their presence in root canals was
      significantly associated with their presence in saliva. The role of yeasts in the
      initiation and perpetuation of periapical disease remains to be determined.

PMID- 12059933
TI  - Penetration of propylene glycol into dentine.
AB  - AIM: This study aimed to evaluate penetration of propylene glycol into root
      dentine. METHODOLOGY: Safranin O in propylene glycol and in distilled water were
      introduced into root canals with and without artificial smear layer. Dye
      diffusion through dentinal tubules was determined spectrophotometrically. The
      time required for dye to exit through the apical foramen using propylene glycol
      and distilled water as vehicles was also determined. The extent and areas of dye
      penetration on the split surfaces of roots were assessed using Adobe Photoshop
      and NIH Image Software. RESULTS: Propylene glycol allowed dye to exit faster
      through the apical foramen. The area and depth of dye penetration with propylene
      glycol was significantly greater than with distilled water (P < 0.0001). Smear
      layer significantly delayed the penetration of dye. CONCLUSION: Propylene glycol
      delivered dye through the root canal system rapidly and more effectively
      indicating its potential use in delivering intracanal medicaments.

PMID- 12059934
TI  - Measurement of strain on tooth roots during post removal with the Eggler post
      remover.
AB  - AIM: The aim was to measure root surface strains in teeth when removing cast
      post/cores with the Eggler post remover. METHODOLOGY: Two groups of 10 teeth each
      were tested: group 1 had 1 mm thickness of dentine coronally, and group 2 had 2
      mm thickness of dentine. After root filling, 10 mm long cast post/cores were
      constructed and cemented with zinc phosphate cement, and strain gauges were
      applied to the roots. The post/cores were removed with the Eggler post remover
      whilst strain measurements were being recorded. Posts were removed twice:
      initially along the long axis of the tooth and then at a 10 degrees angle to the
      long axis. Comparisons between groups 1 and 2 were analysed statistically with
      the Mann-Whitney U-test whilst strains within each group were analysed with the
      Wilcoxon Signed Rank test at the 95% level of confidence. RESULTS: There was no
      significant difference in the strains measured between groups 1 and 2, and no
      significant difference within each group when removing posts along the long axis
      of the tooth and at a 10 degrees angle. Three teeth in group 1 and one tooth in
      group 2 fractured when removing posts at the 10 degrees angle. Three fractures
      were small slivers of dentine at the point where the Eggler's repeller arms
      contacted the tooth mesially and distally, whilst one tooth (from group 1)
      fractured obliquely. CONCLUSIONS: Post removal with the Eggler device is a
      relatively safe procedure but care must be taken when there is a possibility of
      pulling the post out in a nonaxial direction or when less than 1 mm of dentine
      surrounds the apical end of the post.

PMID- 12059935
TI  - Direct amplification of rRNA gene sequences for identification of selected oral
      pathogens in root canal infections.
AB  - AIM: The purpose of this study was to assess the prevalence of selected oral
      pathogens in root canal infections and their relationship with symptoms using a
      highly sensitive technique, the polymerase chain reaction. METHODOLOGY: Samples
      were obtained from 91 infected teeth associated with periradicular lesions,
      including cases of acute periradicular abscesses. DNA was extracted from the
      samples and analysed for the presence of target microbial species using a PCR
      based identification assay. RESULTS: All samples were positive for the presence
      of bacteria. Streptococcus anginosus group was detected in 16.7%, Fusobacterium
      nucleatum in 14.3%, and Bacteroides forsythus in 7.1% of the abscess samples. No
      pus sample yielded Actinomyces israelii, Actinobacillus actinomycetemcomitans or
      fungal species. In general, B. forsythus was found in 20% of the cases (16 of
      80), S. anginosus in 12% (6 of 50), F. nucleatum in 10% (6 of 60) and A. israelii
      in 5% (two of 40). A. actinomycetemcomitans was not detected in any case. Fungi
      were present in only one of 50 cases (2%). There was no correlation between the
      species and symptoms. CONCLUSIONS: Direct molecular approaches appear to be a
      valuable tool for the rapid and reliable diagnosis of infectious diseases, as
      well as for research purposes. There was no correlation between target microbial
      species and symptoms.

PMID- 12059937
TI  - The perceived benefit of endodontic retreatment.
AB  - AIM: There is substantial variation amongst dentists in the management of symptom
      free periapical lesions in root-filled teeth. It has been suggested that this
      variation can be understood as clinicians' choice of different cut-off points on
      a continuous periapical health scale (the 'Praxis Concept (PC) theory'). Based on
      this suggestion, an individual's inclination to propose retreatment can be
      expressed in the Retreatment Preference Score (RPS). In the present study it was
      hypothesized that: (i) the PC theory is valid amongst experienced endodontists;
      and that (ii) interindividual variation in RPS can be explained by a
      corresponding variation in the perceived benefit of endodontic retreatment.
      METHODOLOGY: The RPS was determined for 16 experienced Swedish endodontists. The
      retreatment benefit (RTB) was defined as the gain in utility when a root-filled
      tooth with a persistent periapical lesion ('health state B') moved to a state
      where the lesion had healed ('health state A'). For each individual the utility
      values of the two health states were measured by means of the standard gamble
      technique. RESULTS: The RPS and RTB were found to be subjected to substantial
      inter- and intrarater variation. The decision makers acted in accordance with the
      PC theory. No significant correlation between RPS and RTB was detected.
      CONCLUSIONS: Findings suggest that the PC theory is valid amongst endodontic
      experts. The study did not support the notion that the more potential utility
      that could be produced, the more the individual dentist should tend to perform
      retreatment. However, alternative consequentialist strategies focusing low risk
      taking may be involved.

PMID- 12059936
TI  - In vivo performance of the new non-instrumentation technology (NIT) for root
      canal obturation.
AB  - AIM: The aim of this in vivo study was to compare the radiographic quality of
      root fillings performed by the NIT-obturation method versus conventional
      mechanical obturation. METHODOLOGY: Sixty-six patients needing root canal
      treatment participated in this study. The treatments were performed by three
      private practitioners. The root canals were instrumented with K-Flexofiles to a
      master apical file between sizes 25 and 60, followed by step-back flaring up to
      size 70. Copious irrigation was used throughout the instrumentation procedure
      with NaOCl (3%). The teeth were obturated either by lateral condensation, the
      McSpadden technique (control) or by the new non-instrumentation technology (NIT)
      with and without using gutta-percha points. In the NIT method, a low pressure was
      created within the tooth, and AH 26 sealer was sucked into the root canal system.
      Radiographs of the root-filled teeth were analysed and the length of the root
      filling, the presence of voids and the area of any other fillings determined.
      RESULTS: The root canal fillings of the control group (0.1 +/- 0.1 mm) and those
      of the NIT/gutta-percha group (0.3 +/- 0.1 mm) were both overextended when taking
      the apical constriction as a reference point. Root canal fillings of the
      NIT/gutta-percha group were statistically (P < 0.05) significantly longer than
      those of the NIT without gutta-percha group. The latter showed slightly
      underextended root canal fillings (-0.14 +/- 0.1 mm). CONCLUSIONS: The present
      investigation demonstrated the performance of the NIT-obturation method in vivo.
      Root canals filled by the reduced-pressure-method using sealer combined with
      gutta-percha cones exhibited equivalent radiographic quality compared to
      conventionally filled canals.

PMID- 12059938
TI  - Invasion of vascular cells in vitro by Porphyromonas endodontalis.
AB  - AIM: The objective of this study was to determine whether laboratory strains and
      clinical isolates of microorganisms associated with root canal infections can
      invade primary cultures of cardiovascular cells. METHODOLOGY: Quantitative levels
      of bacterial invasion of human coronary artery endothelial cells (HCAEC) and
      coronary artery smooth muscle cells (CASMC) were measured using a standard
      antibiotic protection assay. Transmission electron microscopy was used to confirm
      and visualize internalization within the vascular cells. RESULTS: Of the
      laboratory and clinical strains tested, only P. endodontalis ATCC 35406 was
      invasive in an antibiotic protection assay using HCAEC and CASMC. Invasion of P.
      endodontalis ATCC 35406 was confirmed by transmission electron microscopy.
      DISCUSSION: Certain microorganisms associated with endodontic infections are
      invasive. If bacterial invasion of the vasculature contributes to the
      pathogenesis of cardiovascular disease, then microorganisms in the pulp chamber
      represent potential pathogens.

PMID- 12059940
TI  - Dynamic torque and apical forces of ProFile.04 rotary instruments during
      preparation of curved canals.
AB  - AIM: To analyse torque and force generated whilst shaping curved canals using
      rotary instruments. METHODOLOGY: A specially designed computer-controlled testing
      platform was used to record events during the shaping of straight and curved
      canals in plastic blocks and in extracted human teeth using ProFile.04
      instruments. Size 40 apical stops were prepared using crown-down, apical
      preparation and step-back procedures. Maximum torque, apically directed force and
      the numbers of revolutions were recorded at a resolution of 100 samples s-1. Load
      causing separation as required by the ISO 3630-1 test and cyclic fatigue was also
      recorded. Mean maximum scores were calculated and statistically tested using one-
      and two-way analyses of variance. RESULTS: Highest and lowest torque scores were
      recorded, respectively, in straight canals in plastic blocks at 25 Nmm and in
      natural canals at 14 Nmm. Significant differences were recorded for canal type
      and preparation phase (P < 0.0001). Loads causing separation varied from 3.7 to
      32.3 Nmm. Apically directed forces ranged from 1 to 7.5 N. Again, there were
      significant differences depending on canal type and preparation phase (P <
      0.0001). The number of revolutions during preparation ranged from 18 to 41. Size
      15, 30 and 45 ProFile.04 instruments separated after 581, 430 and 402
      revolutions, respectively, in a standard cyclic fatigue test. CONCLUSIONS: The
      new torque-testing platform details physical parameters during preparation of
      curved canals. To improve predictability, instrumentation sequences must be
      tested for excessively high torsional moments or forces. This study indicated
      that up to 10 curved canals could be safely prepared with a sequence of ProFile.
      04 rotary instruments without separation due to cyclic fatigue. Efforts should
      continue to correlate root canal anatomy with torque and force generated during
      rotary root canal preparation.

PMID- 12059939
TI  - Effect of three root canal sealers on the retentive strength of endodontic posts
      luted with a resin cement.
AB  - AIM: This investigation examined what effect three different sealers had on
      retention of endodontic posts (Parapost) luted with a resin cement (Panavia 21
      OP). METHODOLOGY: Sixty-four single-rooted teeth were decoronated, filed,
      cleaned, and shaped with a size 5 Gates-Glidden drill and 0.12 taper G.T. rotary
      instrumentation (Dentsply/Tulsa Dental). Teeth were then divided into four groups
      of 16 each. Group 1 was not obturated, and served as a control. The other three
      groups were obturated with gutta-percha using a different sealer for each group.
      Group 2 used a eugenol containing sealer (Kerr Pulp Canal Sealer), group 3 a
      resin sealer (AH-26), and group 4 a calcium hydroxide sealer (Sealapex). After 1
      week's storage at 100% humidity, 10-mm deep post spaces were prepared with a size
      6 Gates-Glidden drill, and size 5 Paraposts were cemented. Following 48 h of
      storage, samples were mounted in a PVC pipe with acrylic, and the posts were
      removed vertically using a universal testing machine at 1 mm min-, with data
      recorded in kilograms. RESULTS: The mean values of force required to remove the
      posts were: group 1 = 61.80, SD = 16.21; group 2 = 43.14, SD = 14.66; group 3 =
      48.54, SD = 17.84; group 4 = 53.52, SD = 18.77. Using anova and Bonferroni tests,
      group 1 demonstrated significantly greater mean retention strength values than
      group 2, but no other significant differences existed between groups. CONCLUSION:
      The chemical formulation of root canal sealers did not significantly affect the
      retention of endodontic posts luted with resin cement.

PMID- 12059941
TI  - Root-canal treatment of a trifid crown premolar.
AB  - AIM: To describe successful root-canal treatment of a permanent maxillary first
      premolar with unusual anatomy. SUMMARY: A diagnosis of irreversible pulpitis of a
      geminated first premolar was made. Clinical and radiographic examination revealed
      a tooth with a trifid crown that joined to give the appearance of a single root
      at the cementoenamel junction. Root-canal treatment involved three separate
      access openings and treating four canals, three of which joined to exit through a
      common foramen. KEY LEARNING POINTS: Symptomatic teeth with morphological
      aberrations can be saved by root-canal treatment. Careful clinical and
      radiographic evaluation are essential, as treatment must be modified to address
      the unusual complexities of the root-canal system(s).

PMID- 12059942
TI  - External cervical resorption associated with localized gingival overgrowth.
AB  - AIM: To describe the presentation and management of an unusual lesion of external
      cervical resorption. SUMMARY: The salient features of this unusual presentation
      of the external cervical resorption with localized gingival overgrowth, and the
      resorption located almost wholly on the labial aspect of a maxillary incisor
      crown are described. Extensive loss of enamel had occurred. The management and
      possible aetiology of the resorptive lesion are discussed. KEY LEARNING POINTS:
      Localized gingival overgrowth can be associated with external cervical
      resorption.The cervical resorption does not necessarily indicate pulp canal
      infection and the need for root-canal treatment.

PMID- 12059945
TI  - The selection and evolution of viral quasispecies in HIV-1 infected children.
AB  - OBJECTIVES: To analyse the diversity and divergence of the viral populations in
      three mother-child pairs in longitudinally obtained samples for up to 7 years.
      METHODS: Peripheral blood mononuclear cells were obtained from three mothers at
      delivery and three to four samples were obtained from each of their children from
      1.5 months up to 78 months of age. The V3 region of HIV-1 was amplified by
      polymerase chain reaction, cloned and sequenced. HIV-1 DNA sequence comparisons
      were performed by phylogenetic analysis. RESULTS: The viral population was
      initially homogenous in two children but highly heterogeneous in one child. Three
      patterns of vertical transmission seemed to have occurred: transmission of the
      most prevalent maternal strain, of a minor maternal strain and of multiple
      maternal strains. In one child, a possible reappearance of a maternal sequence
      was observed at 34 months of age. CONCLUSIONS: Children may become infected with
      the most prevalent maternal strain, a minor maternal variant or multiple maternal
      quasispecies. Maternal viral variants may reappear in children after several
      years of infection and could possibly be derived from a reservoir of founder
      quasispecies established during the children's primary HIV-1 infection.

PMID- 12059946
TI  - Immunological and virological features of HIV-infected patients with increasing
      CD4 cell numbers despite virological failure during protease inhibitor-based
      therapy.
AB  - OBJECTIVES: To investigate the extent of functional T cell recovery and to
      characterize plasma virus and virus producing cells in patients with increasing
      CD4 cell counts despite virological failure during protease inhibitor (PI) based
      therapy. METHODS: The study group included 13 patients who were treated for at
      least 12 months with a PI based regimen and were selected on the basis of a
      sustained immunological response (increase of > 70 CD4 cells/microL) despite
      virological failure (< 1 log10 copies/mL decrease in HIV-1 RNA plasma levels).
      RESULTS: Compared to a historical series of 11 complete responders with less
      advanced disease, the proportion of memory CD4 T cells was significantly higher
      (67.8+/-17.8 vs. 52.8+/-11.0; P=0.045) and the proportion of naive CD4 T cells
      significantly lower (30.5+/-14.8 vs. 45.0+/-10.4, P=0.021) in patients who were
      immunological responders/virological nonresponders. In those patients, ongoing
      viral replication was associated with a strong activation of circulating CD8 T
      lymphocytes; interleukin-2 production remained decreased. CD4 T cell reactivity
      to cytomegalovirus proteins was observed in nine of 11 patients tested. In the
      study group, the proportion of infectious virus present in plasma as well as the
      levels of intracellular viral replication were similar to those measured in
      untreated patients. Virological failure in this group of patients probably
      resulted from pre-existing mutations in the reverse transcriptase gene.
      CONCLUSIONS: This study of patients with increasing CD4 cell numbers despite
      virological failure shows the persistence of immune activation and partial immune
      restoration with no evidence of specific viral dynamics in vivo.

PMID- 12059947
TI  - Levels of IL-6 and soluble IL-6 receptor are increased in HIV patients with a
      history of immune restoration disease after HAART.
AB  - OBJECTIVES: We have previously described immune restoration diseases (IRD)
      associated with asymptomatic opportunistic infections presenting in
      immunodeficient HIV patients responding to highly active antiretroviral therapy
      (HAART). Here we address the question of whether patients with a history of IRD
      exhibit persistent immune activation, shown by elevated levels of interleukin
      (IL)-6 and soluble IL-6 receptor (sIL-6R). METHODS: Peripheral blood mononuclear
      cells (PBMCs) and plasma were collected from HIV patients with nadir CD4 T cell
      counts of < 80/microL and who had achieved immune reconstitution after HAART with
      (n=14) or without (n=15) experiencing IRD, severely immunodeficient (SID)
      patients with < 80 CD4 T cells/microL (n=8) and HIV seronegative controls (n=15).
      PBMC production and plasma levels of IL-6, sIL-6R and interferon (IFN)-gamma
      (PBMC only) were measured by enzyme linked immunosorbent assay (ELISA).
      Intracellular flow cytometry was used to determine the predominant cellular
      source of IL-6 in HIV patients and controls. RESULTS: Unstimulated PBMC from IRD
      patients produced significantly higher amounts of IL-6 and sIL-6R than non-IRD
      patients and HIV seronegative controls. The sIL-6R concentration was also
      significantly higher in supernatants from mitogen-stimulated PBMC from IRD
      patients compared to non-IRD patients. The production of IFN-gamma did not differ
      between IRD and non-IRD patients. IRD patients had significantly higher plasma
      levels of IL-6 compared to non-IRD patients, SID patients and controls. Monocytes
      were the predominant source of IL-6 in both HIV patients and controls.
      CONCLUSIONS: Patients with a history of IRD after HAART have elevated levels of
      IL-6 and sIL-6R.

PMID- 12059948
TI  - Rates of combination antiretroviral treatment change in Australia, 1997-2000.
AB  - OBJECTIVE: To estimate the rate of combination antiretroviral treatment change
      and factors associated with combination antiretroviral treatment change among
      patients recruited in the Australian HIV Observational Database (AHOD). METHODS:
      Analyses were based on patients in the AHOD who had commenced combination
      antiretroviral treatment after 1 January 1997. Combination antiretroviral
      treatment change was defined as the addition or change of at least one
      antiretroviral drug. A random-effect Poisson regression model was used to assess
      factors associated with increased rates of combination antiretroviral treatment
      change. RESULTS: A total of 596 patients in the AHOD were included in the
      analysis, with a median follow-up of 2.3 years. The overall rate of
      antiretroviral treatment change in this group was 0.45 combinations per year. In
      a multivariate analysis, a low CD4 count (< 200 cells/microL) at baseline was
      associated with an increased rate of treatment change [rate ratio (RR)=1.43; 95%
      confidence interval (CI), 1.13, 1.80; P=0.003)]. Combinations including a
      nonnucleoside reverse transcriptase inhibitor were also associated with slower
      rates of change than treatment combinations including a protease inhibitor
      (RR=0.64, 95% CI, 0.51, 0.80, P < 0.001). CONCLUSION: Initiating combination
      antiretroviral at a CD4 cell count < 200 cells/microL may be associated with
      poorer patient outcomes. However, the possibility that clinician or patient
      concerns about low immunological status led to faster rates of treatment change
      in this group cannot be discounted.

PMID- 12059950
TI  - Paediatric antiretroviral therapy audit in South London.
AB  - OBJECTIVES: To audit clinical and surrogate marker outcome data following the
      introduction of combination antiretroviral therapy to HIV-infected children in
      South London. METHODS: We performed a retrospective cohort study of 110 HIV
      infected children under the care of the Paediatric HIV in South London Network
      (PHILS-NET) from January 1996 to September 1999. The following were identified:
      type of antiretroviral therapy used; duration of therapy; toxicity; impact on
      viral load and CD4 count; reasons for changing therapy; and clinical progression.
      RESULTS: Ninety-one (83%) of the 110 children (55 females; median age 6.3 years)
      received 166 antiretroviral therapy regimens. Sixty per cent of the regimens were
      triple therapy: either two nucleoside reverse transcriptase inhibitors (NRTIs)
      and one protease inhibitor (58; 34.9%) or two NRTIs and one non-nucleoside
      reverse transcriptase inhibitor (39; 23.5%). The mean duration of completed
      therapy was 46 weeks for first line therapy with a standard deviation (SD) of 38
      weeks and 40 weeks in third line therapy with an SD of 22 weeks. Changes in
      antiretroviral regimens were owing to virological failure in 60% and toxicity in
      10%. Overall, 46% of children on first line and 37% on second line antiretroviral
      therapy achieved an undetectable viral load of < 400 HIV-1 RNA copies/mL.
      Clinical progression for the whole cohort fell from 3.7% per year for children on
      dual therapy to 0.7% per year for children on highly active antiretroviral
      therapy. CONCLUSIONS: This audit shows the clinical benefit of antiretroviral
      therapy use in a cohort of children with moderately advanced HIV disease. The
      surrogate outcome data seen for the viral load and CD4 count are similar to those
      of reports from clinical trials. Antiretroviral therapy regimens were sequenced
      rapidly, mainly owing to virological failure.

PMID- 12059949
TI  - Long-term efficacy and safety of ritonavir/indinavir at 400/400 mg twice a day in
      combination with two nucleoside reverse transcriptase inhibitors as first line
      antiretroviral therapy.
AB  - OBJECTIVE: To determine the long-term antiretroviral efficacy and tolerability of
      dual protease inhibitor (PI) therapy with indinavir (IDV)/ritonavir (RTV) at
      400/400 mg twice a day (BID) in combination with two nucleoside reverse
      trancriptase inhibitors (NRTIs). DESIGN AND METHODS: In an open-label,
      uncontrolled multicentre clinical trial, antiretroviral therapy naive patients (n
      = 93) with a high median baseline HIV-1 RNA level of 210 000 copies/mL (range 17
      000-2 943 000) and a median CD4 cell count of 195 copies/microL (range 4-656
      copies/microL) were started on a regimen of either zidovudine (ZDV)/lamivudine
      (3TC) (49%), stavudine (d4T)/3TC (38%) or d4T/didanosine (ddI) (14%) plus RTV and
      IDV, each at 400 mg BID. CD4 cell counts and HIV RNA were determined at 4-week
      intervals for a duration of 72 weeks. Statistical analysis was performed on
      treatment as well as by intent to treat, where missing values were counted as
      failures. RESULTS: HIV RNA levels below the limit of detection were achieved in
      59.5% (< 80 copies/mL) and 63% (< 500 copies/mL) of patients according to the
      intent to treat analysis at week 72. In the on treatment analysis, the proportion
      of patients reaching an undetectable viral load was 94.5% (< 80 copies/mL) and
      100% (< 500 copies/mL), respectively. Apart from diarrhoea and nausea, serum
      lipid abnormalities were identified as the most prominent adverse reaction. No
      cases of nephrotoxicity occurred during the entire observation period of 72
      weeks. CONCLUSIONS: Our results demonstrate that quadruple therapy with RTV/IDV
      and two NRTIs induces potent, durable and safe HIV suppression and might be
      particularly beneficial as a first line therapy for patients with a high baseline
      viral load.

PMID- 12059951
TI  - Risk factors for the HIV-associated lipodystrophy syndrome in a closed cohort of
      patients after 3 years of antiretroviral treatment.
AB  - OBJECTIVE: To identify prevalence and risk factors associated with the HIV
      associated lipodystrophy syndrome (HIVLD) after 3 years of antiretroviral
      therapy, to investigate the diagnostic value of anthropometric measures and to
      assess the impact of HIVLD on quality of life. DESIGN AND METHODS: A prospective,
      cross-sectional, multicentre, observational, cohort study was performed in 27
      German teaching hospitals, nonacademic hospitals and private practices. A total
      of 221 HIV-positive patients commencing antiretroviral therapy between July and
      September 1996 were studied. The main outcome measure was lipodystrophy, defined
      as otherwise unexplained truncal fat accumulation and/or fat loss in face or
      extremities. The analysis consisted of multiple logistic regression models,
      receiver operating characteristics (ROC) curves for anthropometric measures and
      visual analogue scales for quality of life. RESULTS: The prevalence of HIVLD
      after 3 years was 34%. The following variables were independently associated with
      HIV-LS: stavudine use > 12 months [odds ratio (OR) 2.1, 95% confidence interval
      (CI) 1.1-3.9], CD4 count nadir < 200 cells/microL (OR 2.2, CI 1.1-4.6),
      hypertriglyceridaemia (OR 2.3, CI 1.3-4.2) and nonnucleoside reverse
      transcriptase inhibitor (NNRTI) intake > 12 months (OR 0.2, CI 0.04-0.87). No cut
      off point was found for anthropometric indices with a sensitivity and specificity
      of > or = 0.8. The mean visual analogue ratings for impaired quality of life, on
      a scale of 0-10, were: 5.2 (self-esteem), 2.9 (social contacts), 4.2 (sexuality)
      and 3.5 (daily activities). CONCLUSIONS: These findings suggest a multifactorial
      aetiology for HIVLD. Stavudine use and a CD4 count below 200 cells/microL may be
      associated with an increased risk for the development of HIVLD. In contrast,
      NNRTI treatment may be associated with a reduced risk. Anthropometric indices
      were found to be insufficient as a diagnostic tool. Quality of life was severely
      affected by HIVLD.

PMID- 12059952
TI  - Thymic activity in late-stage HIV-1 infected individuals receiving highly active
      antiretroviral therapy: potential effect of steroid therapy.
AB  - OBJECTIVE: Our objective was to monitor the effect of steroid therapy on the
      thymic output and function of late-stage HIV-1-infected patients undergoing
      highly active antiretroviral therapy (HAART). DESIGN: The indirect measurement of
      T cells that have recently emigrated from the thymus as a means of quantifying
      thymic output, and therefore thymic function, was achieved through use of the
      polymerase chain reaction-based signal joint T cell receptor rearrangement
      excision circles (sjTREC) assay. Proliferative capacity and interleukin (IL)-2
      and IL-4 production by T cells after antigenic, mitogenic and IL-2 stimulation
      were also analysed. METHOD: Measurements were made of sjTREC levels in peripheral
      blood mononuclear cell DNA samples from five HIV-1 infected patients (one on
      steroid therapy prior to and at the time of sample extraction) receiving HAART.
      IL-2 and IL-4 production and proliferative capacity were also measured in three
      patients, including the patient receiving steroids. RESULT: The sjTREC assay gave
      an extremely weak result for the patient on steroids but, under the same assay
      conditions, provided clear, positive readings for the four patients not on
      steroids. Comparison of the patients' cytokine profiles revealed that IL-2
      production was generally low or absent in all three patients tested but that IL-4
      production was significantly higher in the patient given steroids. Functional
      potential as revealed by proliferation assays showed very low or absent cellular
      proliferation. CONCLUSION: The thymic contribution to the restoration of T
      lymphocyte numbers, particularly during the treatment of HIV-1 infection, may
      become compromised if thymic inhibitory factors such as steroids are used.
      Furthermore, the use of steroids may also favour the development of a T helper 2
      response, which could prove particularly undesirable during HIV-1 infection.

PMID- 12059953
TI  - Adherence to HIV treatment: results from a 1-year follow-up study.
AB  - We evaluated adherence to HIV treatments every 4 months during one year in 63 HIV
      infected subjects using combination therapies including a protease inhibitor. A
      total of 18 subjects reported a high level of adherence, 14 in two evaluations,
      and eight a low level of adherence in all the three evaluations. The remaining 23
      subjects (36.5%) reported different levels of adherence to treatment in the three
      evaluations. These findings suggest that the level of adherence to treatment
      changes markedly for each patient over time.

PMID- 12059954
TI  - The evaluation of metabolic function and fat redistribution in clinical trials.
AB  - Changes in lipid and carbohydrate metabolism and in body composition associated
      with the most potent and effective therapies available are being reported with
      increasing frequency. These changes could potentially lead to increased risks of
      cardiovascular disease. Clinical trials set up to investigate new antiretroviral
      therapies need to explore the therapies' impact on these potentially serious
      adverse outcomes, at least in a subset of patients. The measurements that are
      feasible to include for all patients clearly differ from those required by a
      metabolic substudy. We propose the following: firstly, a minimal set of
      parameters that should be included in all trials; secondly, a desirable set of
      parameters that should be included whenever possible; and thirdly, a list of
      exploratory measures that should be considered. These exploratory measures are
      classified by the different mechanisms for changes in body composition or weight:
      endocrinal, cardiovascular, sterol and chemokine/cytokine pathways. Standardized
      instruments for evaluating patients' reports of body changes and potential
      methods for assessing the risk of cardiovascular disease are described. Minimum
      and desirable standards for methods of measurement are also proposed. The choice
      of parameters is based on expert clinical opinion. The experts consulted include
      investigators from four large ongoing clinical trials with substudies
      specifically designed to investigate lipid and carbohydrate metabolism and
      changes in body composition, together with standard parameters for measurement
      within individual mechanistic pathways. The parameters proposed should be kept
      under review as the body of knowledge about metabolic function and fat
      redistribution in HIV infection increases.

PMID- 12059957
TI  - Control of DNA replication licensing in a cell cycle.
AB  - To maintain genome integrity in eukaryotes, DNA must be duplicated precisely once
      before cell division occurs. A process called replication licensing ensures that
      chromosomes are replicated only once per cell cycle. Its control has been
      uncovered by the discovery of the CDKs (cyclin dependent kinases) as master
      regulators of the cell cycle and the initiator proteins of DNA replication, such
      as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the MCM complex. At
      the end of mitosis, the MCM complex is loaded on to chromatin with the aid of
      ORC, Cdc6/18 and Cdt1, and chromatin becomes licensed for replication. CDKs,
      together with the Cdc7 kinase, trigger the initiation of replication, recruiting
      the DNA replicating enzymes on sites of replication. The activated MCM complex
      appears to play a key role in the DNA unwinding step, acting as a replicating
      helicase and moves along with the replication fork, at the same time bringing the
      origins to the unlicensed state. The cycling of CDK activity in the cell cycle
      separates the two states of replication origins, the licensed state in G1-phase
      and the unlicensed state for the rest of the cell cycle. Only when CDK drops at
      the completion of mitosis, is the restriction on licensing relieved and a new
      round of replication is allowed. Such a CDK-regulated licensing control is
      conserved from yeast to higher eukaryotes, and ensures that DNA replication takes
      place only once in a cycle. Xenopus laevis and mammalian cells have an additional
      system to control licensing. Geminin, whose degradation at the end of mitosis is
      essential for a new round of licensing, has been shown to bind Cdt1 and
      negatively regulate it, providing a new insight into the regulation of DNA
      replication in higher eukaryotes.

PMID- 12059958
TI  - The reaction-diffusion system: a mechanism for autonomous pattern formation in
      the animal skin.
AB  - How do animals acquire their various skin patterns? Although this question may
      seem easy, in fact it is very difficult to answer. The problem is that most
      animals have no related structures under the skin; therefore, the skin cells must
      form the patterns without the support of a prepattern. Recent progress in
      developmental biology has identified various molecular mechanisms that function
      in setting the positional information needed for the correct formation of body
      structure. None of these can explain how skin pattern is formed, however, because
      all such molecular mechanisms depend on the existing structure of the embryo.
      Although little is known about the underlying molecular mechanism, many
      theoretical studies suggest that the skin patterns of animals form through a
      reaction-diffusion system-a putative 'wave' of chemical reactions that can
      generate periodic patterns in the field. This idea had remained unaccepted for a
      long time, but recent findings on the skin patterns of fish have proved that such
      waves do exist in the animal body. In this review, we explain briefly the
      principles of the reaction-diffusion mechanism and summarize the recent progress
      made in this area.

PMID- 12059959
TI  - Characterization of HscC (Hsc62), homologue of Hsp70 in Escherichia coli: over
      expression of HscC modulates the activity of house keeping sigma factor sigma70.
AB  - BACKGROUND: HscC, the third member of the Hsp70 family in Escherichia coli,
      shares 33% identity with the other two homologues, DnaK and HscA, and displays
      ATPase activity. Genetic and biochemical evidence indicates that the DnaK-DnaJ
      chaperone system interacts with sigma32 and is involved in the negative
      regulation of the heat shock response. Although HscC is a highly conserved
      protein in the Hsp70 family, its function is still unknown. RESULTS: We observed
      that the over-expression of HscC caused severe growth inhibition. To explore this
      effect, we performed primer extension analysis and a beta-galactosidase assay and
      found that HscC reduced the sigma70-dependent promoter activity. An in vitro
      transcription assay revealed that HscC inhibited sigma70-dependent transcription.
      In addition, the co-purification analysis showed that sigma70 co-eluted with
      HscC. CONCLUSION: These results indicate that HscC forms a complex with sigma70
      and may function as its negative modulator.

PMID- 12059960
TI  - Cleavage reaction of HDV ribozymes in the presence of Mg2+ is accompanied by a
      conformational change.
AB  - BACKGROUND: Hepatitis delta virus (HDV) ribozymes cleave RNA in the presence of
      divalent metal ions. We have previously elucidated the solution conformation of a
      minimized trans-acting HDV ribozyme and obtained evidence by NMR study that an
      Mg2+ ion binds to a site close to the cleavage site. RESULTS: We examined two
      ribozyme systems: a pre-cleavage complex with a non-cleavable substrate analogue
      (mS8) and a post-cleavage complex with a 3' cleavage product (P7). Upon titration
      with MgCl2, the complex with P7 showed a profound spectral change, while that
      with mS8 showed broadening of the signals. Analysis of the NOESY spectra of the
      P7 complex at high Mg2+ concentration revealed that a G:U pair is formed within
      the L3 loop, and the P1 and P4 stems are stabilized with respect to those of the
      pre-cleavage complex. CONCLUSION: The present analysis indicates that the
      cleavage reaction of the HDV ribozyme produces a big conformational change.
      Furthermore, presence of the 5'-terminal cytidine residue prevents this
      conformational change and its absence stabilizes the product-ribozyme complex in
      the presence of Mg2+. The structure of the Mg2+-bound P7 complex is similar to
      the crystal structure found for a product-ribozyme complex but is different from
      the pre-cleavage structure.

PMID- 12059961
TI  - Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration
      in MDCK cells.
AB  - BACKGROUND: PAR-3 is one of the PAR proteins, previously named ASIP, which are
      indispensable for the establishment of cell polarity in the embryo as well as
      differentiated epithelial cells. In mammalian epithelial cells, it forms a
      ternary complex with aPKC and PAR-6, and is localized to the tight junction that
      has been suggested as being important for creating cell polarity. RESULTS: To
      gain insights into the mode of PAR-3 function in mammalian epithelial cells, we
      examined the effect of PAR-3 over-expression in MDCK cells. Although exogenous
      PAR-3-expression does not affect the epithelial polarity of confluent cells, it
      drastically transforms the morphology of cells at low density into a fibroblastic
      form with developed membrane protrusions. Time-lapse observations have revealed
      that PAR-3 over-expressing cells show intense motility, even after they have
      assembled into loose colonies, suggesting that the contact-mediated inhibition of
      cell migration (CIM) is suppressed. The expressions of E-cadherin and vimentin do
      not change with PAR-3 over-expression, suggesting that exogenous PAR-3 only
      disturbs the endogenous equilibrium of cellular states between a fundamental
      fibroblastic structure and an epithelial one. The co-expression of a dominant
      negative mutant of Rac1 and the addition of nocodazole strongly antagonize the
      effect of PAR-3 over-expression, suggesting the involvement of Rac1 activation
      and microtubule polymerizations. CONCLUSIONS: : The data presented here suggest
      an intriguing link between the contact-mediated inhibition of cell migration and
      the regulation of cell polarity. The putative PAR-3 activities demonstrated here
      may function endogenously in the epithelial cell polarization process by being
      sequestered from the cytosol to the cell-cell junctional regions with aPKC and
      PAR-6 upon cell-cell adhesion.

PMID- 12059962
TI  - CLC-3 deficiency leads to phenotypes similar to human neuronal ceroid
      lipofuscinosis.
AB  - BACKGROUND: CLC-3 is a member of the CLC chloride channel family and is widely
      expressed in mammalian tissues. To determine the physiological role of CLC-3, we
      generated CLC-3-deficient mice (Clcn3-/- ) by targeted gene disruption. RESULTS:
      Together with developmental retardation and higher mortality, the Clcn3-/- mice
      showed neurological manifestations such as blindness, motor coordination deficit,
      and spontaneous hyperlocomotion. In histological analysis, the Clcn3-/- mice
      showed a pattern of progressive degeneration of the retina, hippocampus and ileal
      mucosa, which resembled the phenotype observed in cathepsin D knockout mice. The
      defect of cathepsin D results in a lysosomal accumulation of ceroid lipofuscin
      containing the mitochondrial F1F0 ATPase subunit c. In immunohistochemistry and
      Western blot analysis, we found that the subunit c was heavily accumulated in the
      lysosome of Clcn3-/- mice. Furthermore, we detected an elevation in the endosomal
      pH of the Clcn3-/- mice. CONCLUSIONS: These results indicated that the
      neurodegeneration observed in the Clcn3-/- mice was caused by an abnormality in
      the machinery which degrades the cellular protein and was associated with the
      phenotype of neuronal ceroid lipofuscinosis (NCL). The elevated endosomal pH
      could be an important factor in the pathogenesis of NCL.

PMID- 12059963
TI  - SPAL, a Rap-specific GTPase activating protein, is present in the NMDA receptor
      PSD-95 complex in the hippocampus.
AB  - BACKGROUND: The PSD-95 family of proteins possesses multiple protein binding
      domains, including three PDZ domains, an SH3 domain, a HOOK domain and a
      guanylate kinase-like (GK) domain. The PSD-95 proteins function as scaffolding
      proteins that link ion channels such as the N-methyl-d-aspartate-receptors (NMDA
      Rs) with cytoskeletal networks and signalling molecules, thereby controlling
      synaptic plasticity and learning. RESULTS: We found that the PSD-95 family
      proteins interact via their GK domains with SPA-1-like protein (SPAL), a GTPase
      activating protein (GAP) that is specific for Rap1. SPAL was contained within the
      NMDA-R-PSD-95 complex, and co-localized with PSD-95 and NMDA-R at the synapses in
      cultured hippocampal neurones. Furthermore, NMDA stimulation induced the
      dephosphorylation of SPAL in cultured hippocampal neurones. CONCLUSION: Our
      findings suggest that SPAL may be involved in the NMDA-mediated organization of
      cytoskeletal networks and signal transduction.

PMID- 12059964
TI  - Molecular-feature domains with posterodorsal-anteroventral polarity in the
      symmetrical sensory maps of the mouse olfactory bulb: mapping of odourant-induced
      Zif268 expression.
AB  - Individual glomeruli in the mammalian olfactory bulb presumably represent a
      single type of odourant receptor. Thus, the glomerular sheet provides odourant
      receptor maps at the surface of the olfactory bulb. To understand the basic
      spatial organization of the olfactory sensory maps, we first compared the spatial
      distribution of odourant-induced responses measured by the optical imaging of
      intrinsic signals with that detected immunohistochemically by expressions of
      Zif268, one of the immediate early gene products in juxtaglomerular cells. In the
      dorsal surface of the bulb, we detected a clear correlation in the spatial
      pattern between these responses. In addition, the molecular-feature domains and
      their polarities (spatial shifts of responses with an increase in carbon chain
      length) that were defined by the optical imaging method could be also detected by
      the Zif268 mapping method. We then mapped the Zif268 signals over the entire
      olfactory bulb using a homologous series of fatty acids and aliphatic alcohols as
      stimulus odourants. We superimposed the Zif268 signals onto the standard unrolled
      map with the help of cell adhesion molecule compartments. Each odourant typically
      elicited two pairs of clusters of dense Zif268 signals. The results showed that
      molecular-feature domains and their polarities were arranged symmetrically at
      stereotypical positions in a mirror-image fashion between the lateral and the
      medial sensory maps. The polarity of each domain was roughly in parallel with the
      posterodorsal-anteroventral axis that was defined by the cell adhesion molecule
      compartments. These results suggest that the molecular-feature domain with its
      fixed polarity is one of the basic structural units in the spatial organization
      of the odourant receptor maps in the olfactory bulb.

PMID- 12059965
TI  - Analysis of the function of GABA(B) receptors on inhibitory afferent neurons of
      Purkinje cells in the cerebellar cortex of the rat.
AB  - Purkinje cells, the output neurons of the cerebellar cortex, receive inhibitory
      input from basket, stellate and neighbouring Purkinje cells. The aim of the
      present study was to clarify the role of GABAB receptors on neurons giving
      inhibitory input to Purkinje cells. In sagittal slices prepared from the
      cerebellar vermis of the rat, the GABAB receptor agonist baclofen lowered the
      frequency and amplitude of spontaneous inhibitory postsynaptic currents (IPSCs)
      recorded in Purkinje cells. These effects were prevented by the GABAB receptor
      antagonist CGP 55845. Two mechanisms were involved in the depression of the
      inhibitory input to Purkinje cells. The first mechanism was suppression of the
      firing of basket, stellate and Purkinje cells. The second mechanism was
      presynaptic inhibition of GABA release from terminals of the afferent axons. This
      was indicated by the finding that baclofen decreased the amplitude of IPSCs
      occurring in Purkinje cells synchronously with action potentials recorded in
      basket cells. A further support for the presynaptic inhibition is the observation
      that baclofen decreased the amplitude of autoreceptor currents which are due to
      activation of GABAA autoreceptors at axon terminals of basket cells by
      synaptically released GABA. The presynaptic inhibition was partly due to direct
      inhibition of the vesicular release mechanism, because baclofen lowered the
      frequency of miniature IPSCs recorded in Purkinje cells in the presence of
      cadmium and in the presence of tetrodotoxin plus ionomycin. The results show that
      activation of GABAB receptors decreased GABAA receptor-mediated synaptic input to
      cerebellar Purkinje cells both by lowering the firing rate of the inhibitory
      input neurons and by inhibiting GABA release from their axon terminals with a
      presynaptic mechanism.

PMID- 12059966
TI  - Activity-dependent receptive field changes in the surround of adult cat visual
      cortex lesions.
AB  - Extracellular single cell spike activity was recorded in the visual cortex of
      anaesthetized adult cats at identical sites before and 2 days after focal
      excitotoxic lesions induced by injections of ibotenic acid. In the surround of
      the lesions (up to 5 mm from the border of the lesion), the average postlesion
      receptive field (RF) sizes were not different from the prelesion RFs. However,
      RFs of neurons with increased postlesion excitability were slightly enlarged;
      such neurons were mainly found close to the anterior border of the lesion (< or =
      1 mm). After applying a visual training procedure for 1 h to the postlesion RFs
      (repetitive, synchronous stimulation of a part of the RF and the neighbouring
      unresponsive part of the visual field), there was a small (0.4-0.8 degrees ) but
      significant and specific increase of RF size in about half of the tested neurons.
      This RF enlargement was similar to that observed with the same training procedure
      in the visual cortex of normal cats. Thus, small RF changes can be induced by
      visual stimulation within one hour in normal cells as well as in cells at the
      border of cortical lesions. Any differences between normal and lesioned animals
      appear to be related to lesion-induced changes of excitability.

PMID- 12059967
TI  - Variations in cell density in the ganglion cell layer of the retina as a function
      of ocular pigmentation.
AB  - Ocular melanin regulates retinal development, including cell density gradients in
      the central retina, a region essential for normal visual acuity. In albinos this
      region is underdeveloped and peak cell numbers are reduced. It is not known
      whether there is a dosage relationship between pigmentation and the degree of
      this underdevelopment, as studies of the retinal effects of albinism have
      commonly used rodents. These have poorly developed central regions even in the
      wild type. Rabbits, however, have a unique, highly specialized, visual streak in
      the central retina where cell density gradients are very steep and these are
      reduced in albinos. Here, cell densities in the ganglion cell layer of separate
      groups of rabbits, with different levels of ocular pigmentation and known
      mutations of the tyrosinase gene coding sequence, were examined. These revealed
      reductions in peak cell densities and/or in the regions over which high cell
      densities were maintained in all hypopigmented phenotypes. There was no dosage
      relationship between levels of pigmentation and deficits in the ganglion cell
      layer as animals with relatively small reductions in retinal pigment had deficits
      comparable to those found in albinos. The greatest variability between
      pigmentation phenotypes was between the two completely unpigmented strains.
      Consequently, although pigment may regulate the development of the central
      retina, this study failed to show that it does so in a dose-dependent manner.

PMID- 12059968
TI  - Modulation of Ca2+ currents in rat thalamocortical relay neurons by activity and
      phosphorylation.
AB  - Rhythmic low and high frequency activity in thalamocortical networks depend
      critically on activation of low- and high-voltage-activated (LVA, HVA) Ca2+
      currents. In order to test whether Ca2+ currents are modified during repetitive
      activation, acutely isolated thalamocortical relay neurons of rats, at postnatal
      days 12 (P12) to P20, were investigated using patch-clamp, Ca2+ imaging and
      Western blot techniques. High-voltage-activated, but not LVA Ca2+ currents were
      reduced significantly during 2 Hz stimulation. Ca2+ imaging experiments
      demonstrated a close correlation between the increase in intracellular Ca2+
      levels and the decrease in HVA Ca2+ current amplitudes. Further examination of
      HVA Ca2+ currents revealed a 'U-shaped' inactivation curve and a time-dependent
      inactivation process that could be described by a two-exponential function. The
      'U-shape' was significantly reduced, current amplitude was increased
      significantly and time-dependent inactivation revealed a one-exponential decline
      with Ba2+ as the charge carrier, following activation of the cAMP/PKA pathway,
      and following application of phosphatase inhibitors (ascomycin, calyculin A).
      Western blot analysis and the effect of ascomycin indicated an involvement of
      calcineurin in the inactivation process. Isolation of HVA Ca2+ current components
      by subtype-specific blockers revealed that changes in time-dependent
      inactivation, inactivation curve and current amplitude were carried mainly by L
      type and N-type Ca2+ currents. Furthermore, Ca2+-dependent inactivation was
      operative during stimulation protocols mimicking tonic action potential firing.
      These data indicate a modulation of L- and N-type Ca2+ channels by
      phosphorylation, resulting jointly in an increased intracellular Ca2+ influx
      during activity of the ascending brainstem system, the latter occurring during
      states of wakefulness.

PMID- 12059969
TI  - Cell-specific expression of the glutamine transporter SN1 suggests differences in
      dependence on the glutamine cycle.
AB  - Glutamine is involved in a variety of metabolic processes, including recycling of
      the neurotransmitters glutamate and gamma-aminobutyric acid (GABA). The system N
      transporter SN1 mediates efflux as well as influx of glutamine in glial cells
      [Chaudhry et al. (1999), Cell, 99, 769-780]. We here report qualitative and
      quantitative data on SN1 protein expression in rat. The total tissue
      concentrations of SN1 in brain and in kidney are half and one-quarter,
      respectively, of that in liver, but the average concentration of SN1 could be
      higher in astrocytes than in hepatocytes. Light and electron microscopic
      immunocytochemistry shows that glutamatergic, GABAergic and, surprisingly, purely
      glycinergic boutons are ensheathed by astrocytic SN1 laden processes, indicating
      a role of glutamine in the production of all three rapid transmitters. A
      dedication of SN1 to neurotransmitter recycling is further supported by the lack
      of SN1 immunoreactivity in oligodendrocytes (cells rich in glutamine but without
      perisynaptic processes). All neuronal structures appear unlabelled implying that
      a different protein mediates glutamine uptake into nerve endings. In several
      regions, SN1 immunoreactivity is higher in association with GABAergic than
      glutamatergic synapses, in agreement with observations that exogenous glutamine
      increases output of transmitter glutamate but not GABA. Nerve terminals with low
      transmitter reuptake or high prevailing firing frequency are associated with high
      SN1 immunoreactivity in adjacent glia. Bergmann glia and certain other astroglia
      contain very low levels of SN1 immunoreactivity compared to most astroglia,
      including retinal Muller cells, indicating the possible existence of SN isoforms
      and alternative mechanisms for transmitter recycling.

PMID- 12059970
TI  - Pineal arylalkylamine N-acetyltransferase gene expression is highly stimulated at
      night in the diurnal rodent, Arvicanthis ansorgei.
AB  - The different mechanisms underlying the control of diurnal vs. nocturnal activity
      are still unknown. Regarding the nocturnal synthesis of the pineal hormone,
      melatonin, experiments performed on diurnal sheep or bovine and on nocturnal rat
      or hamster revealed important differences in the regulation of the melatonin rate
      limiting enzyme, arylalkylamine N-acetyltransferase (AA-NAT). These observations
      raised the hypothesis that melatonin synthesis may be different in nocturnal vs.
      diurnal animals. In this study, we cloned the cDNA coding for Aa-nat and analysed
      the mechanisms of AA-NAT enzyme activation in the pineal gland of the diurnal
      grass rat, Arvicanthis ansorgei, and compared them to those of the nocturnal
      Wistar rat, Rattus norvegicus. Aa-nat gene sequences of both species are 86.6%
      identical. In Arvicanthis, Aa-nat gene expression is markedly increased at the
      beginning of the night and is followed by a large increase in AA-NAT activity and
      melatonin content. In contrast, at the end of the night, the decrease in AA-NAT
      activity and melatonin content precedes that of Aa-nat mRNA. A beta-adrenergic
      agonist given at daytime reproduces the nocturnal activation of melatonin
      synthesis, whereas, a beta-adrenergic antagonist given at night-time inhibits AA
      NAT activity and melatonin synthesis independently of Aa-nat mRNA. The day-night
      regulation of melatonin synthesis in the pineal of the diurnal Arvicanthis,
      involving a transcriptional activation in early night and a post-translational
      inhibition at late night, is very similar to that of the nocturnal Wistar rat. In
      conclusion, the fundamental differences underlying melatonin synthesis among
      species rely upon phylogenetic rather than behavioural differences.

PMID- 12059971
TI  - Metabotropic glutamate receptors mediate expression of LTP in slices of rat
      visual cortex.
AB  - Long-term-potentiation (LTP) can be induced by application of a standard theta
      burst stimulation protocol in slice preparations of the neocortex. This type of
      LTP is known to be dependent on the activation of NMDA receptors. The present
      study used specific experimental conditions to evoke a non-NMDA receptor mediated
      type of LTP. By use of weak theta-burst stimulation (wTBS) we describe a non-NMDA
      receptor dependent LTP in rat visual cortex in vitro, which is sensitive to an
      antagonist of metabotropic glutamate receptors (mGluR). In slices of the visual
      cortex we stimulated ascending inputs in cortical layer IV and recorded
      extracellular field potentials (FPs) from cortical layers II/III. In disinhibited
      slices (with 1 microm picrotoxin), a wTBS induced LTP to 138% of control. The
      expression of this potentiation was insensitive to the NMDA-receptor antagonist,
      D-AP5, but could be abolished by application of the mGluR antagonist MCPG. These
      data suggest an NMDA-independent mechanism for LTP induction in the visual cortex
      which can be observed in layer II/III neurons.

PMID- 12059972
TI  - Programmed cell death in the neurulating embryo is prevented by the chaperone
      heat shock cognate 70.
AB  - Neuronal cell death is a genuine developmental process, with precise regulation
      and defined roles. In striking contrast, characterization of cell death that
      occurs at early stages of neural development is very limited. We previously
      showed that embryonic proinsulin increases the level of the chaperone heat shock
      cognate 70 (Hsc70) and reduces the incidence of apoptosis in the neurulating
      chick embryo [de la Rosa, et al. (1998), Proc. Natl. Acad. Sci. USA, 95, 9950].
      We now demonstrate that Hsc70 is directly involved in cell survival during
      neurulation, as specific downregulation of endogenous Hsc70 by antisense
      oligodeoxynucleotide interference provoked an increase in apoptosis both in vitro
      and in ovo. In parallel, activation of caspase-3 was increased after hsc70
      antisense oligodeoxynucleotide treatment. Dead cells were located mostly in the
      developing nervous system, distributed in areas where the incidence of cell death
      was high. These areas coincided both in vivo and under different death-inducing
      conditions, including antisense interference and growth factor deprivation. Hsc70
      immunostaining was strong in at least some areas of high cell death. Apoptotic
      cells within these areas presented undetectable Hsc70 levels, however, suggesting
      that this protein acts as an intrinsic protector of neuroepithelial and neural
      precursor cells.

PMID- 12059973
TI  - Contralateral inhibition as a sensory bias: the neural basis for a female
      preference in a synchronously calling bushcricket, Mecopoda elongata.
AB  - Imperfect synchrony between male calls occurs widely in acoustically courting
      crickets and bushcrickets. Males which are able to establish the temporal
      leadership usually attract more females in choice experiments but the proximate
      mechanism for this precedence effect is unknown. Here we show that contralateral
      inhibition, the neural basis for lateral contrast enhancement in the auditory
      pathways of insects and vertebrates, is also the probable proximate neural
      mechanism for this female preference. We recorded simultaneously from a pair of
      identified auditory interneurons in the synchronizing bushcricket Mecopoda
      elongata. When two identical acoustic stimuli are presented from opposite
      directions, one preceding the other by 120 ms, the neural representation within
      the receiver is far stronger for the leader signal. This results from a
      suppression of the neural response to the follower chirp by reciprocal
      contralateral inhibition. The advantage of the representation of the leader is 2
      3-fold with time delays between 70 and 130 ms; the most clear-cut female
      preferences have also been found with such delays in previous behavioural
      experiments. In time-intensity trading experiments, a lead by 120 ms could only
      be compensated for by increasing the amplitude of the follower signal by 7-11 dB.
      We discuss contralateral inhibition in auditory systems as a sensory bias that
      results in female preference for leading signals, with important evolutionary
      consequences for male calling strategies.

PMID- 12059974
TI  - Expression of fractalkine and its receptor, CX3CR1, in response to ischaemia
      reperfusion brain injury in the rat.
AB  - Fractalkine is a neuronally expressed chemokine that acts through its G-protein
      coupled receptor CX3CR1, localized on microglial and immune cells. Fractalkine
      might be involved in neuroinflammatory processes secondary to neuronal damage,
      which normally occur in a time frame of days after ischaemia. We evaluated by in
      situ hybridization and immunohistochemistry the expression of fractalkine and
      CX3CR1 in the rat brain, after a transient occlusion of the middle cerebral
      artery. We found that at 12 h after ischaemia neuronal fractalkine expression was
      transiently increased in scattered necrotic neurons of the cortex and lost from
      the ischaemic striatum. At 24 and 48 h after ischaemia, fractalkine
      immunoreactivity was strongly increased in morphologically intact cortical
      neurons of the ischaemic penumbra where also the stress-inducible HSP-72 was
      strongly up-regulated. The intensity of fractalkine immunoreactivity of neurons
      in the penumbra returned to basal levels at 7 days after ischaemia. Fractalkine
      synthesis was also induced in endothelial cells of the infarcted area, at 48 h
      and 7 days after ischaemia. CX3CR1 expression was detected in the activated
      microglial cells of the ischaemic tissue 24 and 48 h after ischaemia, and became
      strongly up-regulated in macrophages/phagocytic microglia inside the infarcted
      tissue 7 days after ischaemia. These data suggest that fractalkine may
      participate in the activation and chemoattraction of microglia into the infarcted
      tissue, and contribute to the control of leucocyte trafficking from blood vessels
      into the injured area.

PMID- 12059975
TI  - Endogenous histamine in the medial septum-diagonal band complex increases the
      release of acetylcholine from the hippocampus: a dual-probe microdialysis study
      in the freely moving rat.
AB  - The effects of histaminergic ligands on both ACh spontaneous release from the
      hippocampus and the expression of c-fos in the medial septum-diagonal band (MSA
      DB) of freely moving rats were investigated. Because the majority of cholinergic
      innervation to the hippocampus is provided by MSA-DB neurons, we used the dual
      probe microdialysis technique to apply drugs to the MSA-DB and record the induced
      effects in the projection area. Perfusion of MSA-DB with high-KCl medium strongly
      stimulated hippocampal ACh release which, conversely, was significantly reduced
      by intra-MSA-DB administration of tetrodotoxin. Histamine or the H2 receptor
      agonist dimaprit, applied directly to the hippocampus, failed to alter ACh
      release. Conversely, perfusion of MSA-DB with these two compounds increased ACh
      release from the hippocampus. Also, thioperamide and ciproxifan, two H3 receptor
      antagonists, administered into MSA-DB, increased the release of hippocampal ACh,
      whereas R-alpha-methylhistamine, an H3 receptor agonist, produced the opposite
      effect. The blockade of MSA-DB H2 receptors, caused by local perfusion with the
      H2 receptor antagonist cimetidine, moderated the spontaneous release of
      hippocampal ACh and antagonized the facilitation produced by H3 receptor
      antagonists. Triprolidine, an H1 receptor antagonist, was without effect.
      Moreover, cells expressing c-fos immunoreactivity were significantly more
      numerous in ciproxifan- or thioperamide-treated rats than in controls, although
      no colocalization of anti-c-fos and anti-ChAT immunoreactivity was observed.
      These results indicate a role for endogenous histamine in modulating the
      cholinergic tone in the hippocampus.

PMID- 12059976
TI  - Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial
      prefrontocortical dendrites: implications for stress-related cortical pathology?
AB  - Stress has been shown to affect brain structural plasticity, promote long-term
      changes in multiple neurotransmitter systems and cause neuronal atrophy. However,
      the mechanisms involved in these stress-related neural alterations are still
      poorly understood. Mitogen-activated protein kinase (MAPK) cascades play a
      crucial role in the transduction of neurotrophic signal from the cell surface to
      the nucleus and are implicated in the modulation of synaptic plasticity and
      neuronal survival. An intriguing possibility is that stress might influence brain
      plasticity through its effects on selective members of such intracellular
      signalling cascades responsible for the transduction of neurotrophin signals.
      Here, we have investigated the effects of stress on the expression of three
      members of the MAPK/extracellular-regulated kinase (ERK) pathway such as phospho
      ERK1, phospho-ERK2 and phospho-cAMP/calcium-responsive element-binding protein
      (CREB) in the adult rat brain. Male rats were subjected to mild footshocks and
      the patterns of protein expression were analysed after 21 consecutive days of
      stress. We found that chronic stress induced a pronounced and persistent ERK1/2
      hyperphosphorylation in dendrites of the higher prefrontocortical layers (II and
      III) and a reduction of phospho-CREB expression in several cortical and
      subcortical regions. We hypothesized that defects in ERK signalling regulation
      combined with a reduced phospho-CREB activity may be a crucial mechanism by which
      sustained stress may induce atrophy of selective subpopulations of vulnerable
      cortical neurons and/or distal dendrites. Thus, ERK-mediated cortical
      abnormalities may represent a specific path by which chronic stress affects the
      functioning of cortical structures and causes selective neural network defects.

PMID- 12059977
TI  - Creatine kinase B-driven energy transfer in the brain is important for
      habituation and spatial learning behaviour, mossy fibre field size and
      determination of seizure susceptibility.
AB  - Creatine kinases are important in maintaining cellular-energy homeostasis, and
      neuroprotective effects have been attributed to the administration of creatine
      and creatine-like compounds. Herein we examine whether ablation of the cytosolic
      brain-type creatine kinase (B-CK) in mice has detrimental effects on brain
      development, physiological integrity or task performance. Mice deficient in B-CK
      (B-CK-/-) showed no gross abnormalities in brain anatomy or mitochondrial
      ultrastructure, but had a larger intra- and infrapyramidal mossy fibre area.
      Nuclear magnetic resonance spectroscopy revealed that adenosine triphosphate
      (ATP) and phosphocreatine (PCr) levels were unaffected, but demonstrated an
      apparent reduction of the PCr left arrow over right arrow ATP phosphorus exchange
      capacity in these mice. When assessing behavioural characteristics B-CK-/-
      animals showed diminished open-field habituation. In the water maze, adult B-CK-/
      mice were slower to learn, but acquired the spatial task. This task performance
      deficit persisted in 24-month-old, aged B-CK-/- mice, on top of the age-related
      memory decline normally seen in old animals. Finally, a delayed development of
      pentylenetetrazole-induced seizures (creating a high-energy demand) was observed
      in B-CK-/- mice. It is suggested that the persistent expression of the
      mitochondrial isoform ubiquitous mitochondrial CK (UbCKmit) in the
      creatine/phospho-creatine shuttle provides compensation for the loss of B-CK in
      the brain. Our studies indicate a role for the creatine-phosphocreatine/CK
      circuit in the formation or maintenance of hippocampal mossy fibre connections,
      and processes that involve habituation, spatial learning and seizure
      susceptibility. However, for fuelling of basic physiological activities the role
      of B-CK can be compensated for by other systems in the versatile and robust
      metabolic-energy network of the brain.

PMID- 12059978
TI  - Upregulation and activation of the Nrf-1 transcription factor in the lesioned
      hippocampus.
AB  - The Nrf-1 and Nrf-2 transcription factors play a pivotal role in the cellular
      defence against the toxic effects of reactive oxygen species (ROS). Although ROS
      are key effectors of neuronal death after ischaemic and traumatic brain injury,
      it is not known whether Nrf-1 and Nrf-2 are involved in neuroprotective
      signalling. Here, we analysed the temporal and spatial expression pattern of Nrf
      1 and Nrf-2 after unilateral excitotoxic lesion of mouse hippocampus. In marked
      contrast to previous in vitro studies, where upregulation of these transcription
      factors on the mRNA level was never detected, we found a strong induction of Nrf
      1 mRNA and protein expression in neurons of the lesioned hippocampus, accompanied
      by a weak elevation of Nrf-2 mRNA levels. Nrf-1 predominantly localized to the
      nucleus in the injured hippocampus. Furthermore, expression of the cytoprotective
      enzyme, heme oxygenase-1, a major target of Nrf-1 and Nrf-2 action, was
      coregulated with Nrf-1 in the same hippocampal neurons, suggesting that Nrf-1 is
      functionally active. Because Nrf-1 and Nrf-2 are potent inducers of various
      cytoprotective proteins, our data suggest a role of Nrf-1 and Nrf-2 in neuronal
      survival after acute brain injury.

PMID- 12059979
TI  - Opposing roles for medial and central amygdala in the initiation of noradrenergic
      cell responses to a psychological stressor.
AB  - Psychological stressors trigger the activation of medullary noradrenergic cells,
      an effect that has been shown to depend upon yet-to-be-identified structures
      located higher in the brain. To test whether the amygdala is important in this
      regard, we examined the effects of amygdala lesions on noradrenergic cell
      responses to restraint, and also looked at whether any amygdala cells that
      respond to restraint project directly to the medulla. Ibotenic acid lesions of
      the medial amygdala completely abolished restraint-induced Fos expression in A1
      and A2 noradrenergic cells. In contrast, lesions of the central amygdala actually
      facilitated noradrenergic cell responses to restraint. Tracer deposits in the
      dorsomedial (but not ventrolateral) medulla retrogradely labelled many cells in
      the central nucleus of the amygdala, but none of these cells expressed Fos in
      response to restraint. These data suggest for the first time that the medial
      amygdala is critical to the activation of medullary noradrenergic cells by a
      psychological stressor whereas the central nucleus exerts an opposing, inhibitory
      influence upon noradrenergic cell recruitment. The initiation of noradrenergic
      cell responses by the medial amygdala does not involve a direct projection to the
      medulla. Accordingly, a relay through some other structure, such as the
      hypothalamic paraventricular nucleus, warrants careful consideration.

PMID- 12059981
TI  - Cardiovascular secrets of secretory phospholipase A(2).

PMID- 12059982
TI  - Biological effects of secretory phospholipase A(2) group IIA on lipoproteins and
      in atherogenesis.
AB  - Secretory phospholipase A(2) group IIA(sPLA(2) IIA) can be produced and secreted
      by various cell types either constitutionally or as an acute-phase reactant upon
      stimulation by proinflammatory cytokines. The enzyme prefers
      phosphatidylethanolamine and phosphatidylserine as substrates. One important
      biological function may be the hydrolytic destruction of bacterial membranes. It
      has been demonstrated, however, that sPLA(2) can also hydrolyse the phospholipid
      monolayers of high density lipoprotein (HDL) and low density lipoprotein (LDL) in
      vitro. Secretory phospholipase A(2)-modified LDL show increased affinity to
      glycosaminoglycans and proteoglycans, a tendency to aggregate, and an enhanced
      ability to deliver cholesterol to cells. Incubation of cultured macrophages with
      PLA(2)-treated LDL and HDL is associated with increased intracellular lipid
      accumulation, resulting in the formation of foam cells. Elevated sPLA(2)(IIA)
      activity in blood serum leads to an increased clearance of serum cholesterol.
      Secretory phospholipase A(2)(IIA) can also be detected in the intima, adventitia
      and media of the atherosclerotic wall not only in developed lesions but also in
      very early stages of atherosclerosis. The presence of DNA of Chlamydia
      pneumoniae, herpes simplex virus, and cytomegalovirus was found to be associated
      with sPLA(2)(IIA) expression and other signs of local inflammation. Thus,
      sPLA(2)(IIA) appears to be one important link between the lipid and the
      inflammation hypothesis of atherosclerosis.

PMID- 12059983
TI  - Relevance of apoptosis and cell proliferation for survival of patients with
      dilated cardiomyopathy undergoing partial left ventriculectomy.
AB  - BACKGROUND: Cardiomyocyte apoptosis as well as proliferation have been described
      in congestive heart failure, but their clinical relevance remains unclear. In
      order to clarify whether apoptosis and cell proliferation occur in patients with
      idiopathic dilated cardiomyopathy and whether their degree in left ventricle
      fragments resected during partial left ventriculectomy has any influence on the
      outcome after this surgery, we compared their occurrence in four groups of
      patients: group A, short-term survivors (n = 18); group B, deaths within 6 months
      of the surgery (n = 13); group C, long-term survivors (n = 12); and Group D,
      deaths within 60 months (n = 19). DESIGN: Apoptotic cardiomyocytes and
      interstitial cells were quantified in left ventricle fragments from 31 patients
      with idiopathic-dilated cardiomyopathy using the TUNEL assay. Cell proliferation
      was quantified in parallel sections by KI-67 immunohistochemistry. RESULTS:
      Apoptotic cells were present in the majority of cases (n = 24) and proliferative
      cells in all cases. Whereas there was no significant difference regarding all
      parameters examined between Groups A and B, there was a highly significant
      difference between Groups C and D in the number of apoptotic cardiomyocytes (P =
      0.012) and apoptotic interstitial cells (P = 0.006). There was no significant
      relationship between apoptotic cardiomyocytes and KI-67-positive cardiomyocytes,
      but a negative correlation between apoptotic interstitial cells and KI-67
      positive interstitial cells (r = -0.383; P = 0.028). CONCLUSION: Cardiomyocyte
      apoptosis and proliferation occur in the majority of patients with idiopathic
      dilated cardiomyopathy. High numbers of apoptotic cardiomyocytes and apoptotic
      interstitial cells are significantly related to a bad late outcome after partial
      left ventriculectomy.

PMID- 12059984
TI  - Oestrogen receptor gene variation is a determinant of coronary reactivity in
      healthy young men.
AB  - BACKGROUND: Oxidised low-density lipoprotein (ox-LDL) is a determinant of
      impaired coronary function and oestrogens inhibit its formation probably
      throughout genetically-variable oestrogen receptor 1 (ESR1) in artery wall. We
      hypothesized that the ESR1 polymorphism might influence coronary function and
      reactivity as measured by positron emission tomography (PET), which allows the
      detection of coronary dysfunction before appearance of angiographic lesions.
      MATERIALS AND METHODS: Fifty-one healthy young men (aged 35 +/- 4 years), with
      normal or slightly-elevated serum cholesterol, underwent PET with intravenous
      adenosine. ESR1 PvuII genotypes P/P, P/p, and p/p in addition to the plasma
      autoantibody titre against ox-LDL, a marker of in vivo oxidation, were
      determined. RESULTS: The ESR1 genotype persisted as the only significant
      predictor of adenosine stimulated coronary flow (P = 0.035) after adjustment for
      other coronary risk factors. Subjects with P/P genotype had 33.4 and 41.8% lower
      adenosine-stimulated flow values than subjects with P/p and p/p genotypes (P =
      0.030). Furthermore, plasma levels of ox-LDL titre were on average 59 and 77%
      higher in subjects with P/P genotype than in subjects with P/p or p/p genotypes
      (P = 0.049). CONCLUSIONS: These tentative findings from our pilot study provide
      evidence that genetic variation in ESR1 may modify coronary reactivity and LDL
      oxidation and reflect differences in the early pathogenesis of coronary
      dysfunction in these healthy young men.

PMID- 12059985
TI  - Complement activating antibodies against the human 60 kDa heat shock protein as a
      new independent family risk factor of coronary heart disease.
AB  - BACKGROUND: Several groups have reported high levels of antibodies against 60 kDa
      heat shock proteins (hsp) associated with coronary heart disease. METHODS AND
      RESULTS: Complement activating (CA) antihsp60 autoantibodies were measured by the
      AtheroRisk kit (CardioPath Ltd, Alloa, UK), in parallel with IgG antibodies to
      human hsp60 and mycobacterial hsp65 by ELISA in 32 healthy children (18 boys, 14
      girls, 11.8 +/- 4.0 years). At least one of the parents of these children had a
      history of myocardial infarction before 55 years of age (high family risk (HFR)
      group). The control group consisted of 63 healthy children (31 boys, 32 girls,
      9.0 +/- 3.6 years) without known family history of coronary heart disease (CHD),
      hypertension, and diabetes mellitus. Concentrations of CA antihsp60 antibodies
      were significantly (P = 0.021) higher in the HFR group than in the control group.
      Also in the HFR group, significantly (P = 0.004) lower high-density lipoprotein
      cholesterol (HDL-C)-cholesterol (measured enzymatically) and significantly (P =
      0.020) higher low-density lipoprotein cholesterol (LDL-C)-cholesterol levels
      (calculated by the Friedewald formula) were observed when compared with the
      controls. The difference in the CA antihsp60 antibody levels between the HFR and
      control groups remained significant even after adjustments for age, smoking, HDL
      cholesterol, LDL-cholesterol levels, and white blood cell count. Children with
      high (in the highest quartile) CA antihsp60 antibody levels compared with those
      with normal levels of these antibodies also had adjusted odds ratios (OR) of 9.80
      (2.15-44.58, P = 0.003), indicating high family risk. No significant difference
      in the IgG antihsp antibody levels was observed. CONCLUSIONS: These findings
      indicate that high levels of CA autoantibodies against hsp60 can be considered to
      be a novel family risk factor of CHD, independent of HDL- and LDL-cholesterol
      levels.

PMID- 12059986
TI  - Glucocorticoids and 11 beta-hydroxysteroid dehydrogenase type 2 gene expression
      in the aging kidney.
AB  - BACKGROUND: Aging is associated with increased concentrations of circulating
      glucocorticoids, a situation expected to induce a glucocorticoid-mediated
      mineralocorticoid effect, resulting in sodium retention and hypertension unless
      counteracting mechanisms are operative. Conversion of glucocorticoids to inert 11
      beta-keto compounds by the enzyme 11 beta-hydroxysteroid dehydrogenase type 2 (11
      beta-HSD2) is one of these mechanisms. We hypothesized therefore that 11 beta
      HSD2 gene expression and/or activity increase with age in male WAG/Rij rats, a
      strain without increased blood pressure with age or senescence-related obesity or
      kidney disease. MATERIALS AND METHODS: Corticosterone (B) concentrations in
      plasma and urinary excretion of corticosterone and dehydrocorticosterone (A)
      tetrahydro metabolites, THB + 5 alpha-THB + THA, were assessed by gas
      chromatography-mass spectrometry (GC-MS) in 10-month-old-rats (n = 6) and in 30
      month-old rats (n = 6). Renal 11 beta-HSD2 messenger ribonucleic acid (mRNA)
      abundance was measured by real-time quantitative TaqMan polymerase chain reaction
      and microarray assays. RESULTS: Thirty-month-old rats had significantly higher
      corticosterone concentrations in plasma and increased urinary excretion of
      corticosterone and dehydrocorticosterone tetrahydro metabolites. Conversion of B
      to A in kidney microsomes from 30-month-old rats was moderately but not
      significantly increased compared with 10-month-old rats. The urinary ratios of
      (THB + 5 alpha-THB)/THA and free B/A and renal 11 beta-HSD2 mRNA abundance were
      equal in 10- and 30-month-old rats. CONCLUSIONS: There is no evidence for an
      enhanced gene expression or activity of renal 11 beta-HSD2 in these aging rats,
      suggesting either that endogenous 11 beta-HSD2 is able to cope with the increased
      corticosterone concentrations characteristic of the aging process or that
      alternative mechanisms contribute to the maintenance of a normal sodium excretion
      in these animals.

PMID- 12059987
TI  - Allelic polymorphism -491A/T in apo E gene modulates the lipid-lowering response
      in combined hyperlipidemia treatment.
AB  - BACKGROUND: Combined hyperlipidemia (CHL) is one of the dyslipidemias more
      frequently found in clinical practice, and lipid-lowering drugs are often
      necessary in its management. Some genetic loci have been associated with CHL
      expression, and some studies have shown modulation of drugs efficiency in the
      treatment of dyslipidemias by genetic polymorphisms. We have investigated whether
      common polymorphisms and mutations in the apolipoprotein (apo) E, lipoprotein
      lipase (LPL), and apo CIII genes influence atorvastatin or bezafibrate responses
      in patients with CHL. DESIGN: One hundred and sixteen subjects participating in
      the ATOMIX study (Atorvastatin in Mixed dyslipidemia) were randomized to
      treatment with either atorvastatin or bezafibrate. Apolipoprotein E genotype and
      common -491A/T and -219T/G polymorphisms in the apo E gene promoter region, Sst I
      polymorphism in the apo CIII gene (3238C/G), and D9N and N291S common mutations
      in the LPL gene were determined by polymerase chain reaction (PCR) and
      restriction enzyme digestion. RESULTS: Statistical analysis showed the influence
      of the -491A/T polymorphism in atorvastatin and bezafibrate treatments. Subjects
      carrying the -491T allele showed an increased LDL-cholesterol-lowering effect
      with atorvastatin compared with -491T allele noncarriers (-35% vs. -27%, P =
      0.037). Subjects carrying the -491T allele, when on bezafibrate treatment, showed
      a lower triglyceride reduction compared with -491T allele noncarriers (-23% vs. 
      39%, P = 0.05). CONCLUSIONS: In our study, the -491A/T polymorphism in the apo E
      gene promoter region modulated the lipid-lowering efficiency of atorvastatin and
      bezafibrate in CHL patients. Such influence might explain some of the
      interindividual response variabilities observed for the two drugs, and could help
      in CHL management.

PMID- 12059988
TI  - Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in
      visceral obesity.
AB  - BACKGROUND: Dyslipidaemia may account for increased risk of cardiovascular
      disease in central obesity. Pharmacotherapy is often indicated in these patients,
      but the optimal approach remains unclear. We investigated the effects of
      atorvastatin and fish oil on plasma lipid and lipoprotein levels, including
      remnant-like particle-cholesterol and apolipoprotein C-III, in dyslipidaemic men
      with visceral obesity. METHODS: We carried out a 6-week randomized, placebo
      controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg day(-1))
      and fish oil (4 g day(-1)) on plasma lipids and lipoproteins in 52 obese men (age
      53 +/- 1 years, BMI 33.7 +/- 0.55 kg m(-2)) with dyslipidaemia and insulin
      resistance. Treatment effects were analysed by general linear modelling. RESULTS:
      Atorvastatin had significant main effects in decreasing triglycerides (-0.38 +/-
      0.02 mmol L(-1), P = 0.002), total cholesterol (-1.89 +/- 0.17 mmol L(-1), P =
      0.001), LDL-cholesterol (-1.78 +/- 0.14 mmol L(-1), P = 0.001), remnant-like
      particle-cholesterol (-0.08 +/- 0.04 mmol L(-1), P = 0.035), apolipoprotein B (
      49 +/- 4 mg dL(-1), P = 0.001), apolipoprotein C-III (-12.6 +/- 6.1 mg L(-1), P =
      0.044) and in increasing HDL-cholesterol (+0.10 +/0- 0.04 mmol L(-1), P = 0.007).
      Fish oil had significant main effects in decreasing triglycerides (-0.38 +/- 0.11
      mmol L(-1), P = 0.002) and in increasing HDL-cholesterol (+0.07 +/- 0.04 mmol L(
      1), P = 0.041). There were no significant changes in weight or insulin resistance
      during the study. CONCLUSIONS: Atorvastatin and fish oil have independent and
      additive effects in correcting dyslipidaemia in viscerally obese men. Improvement
      in abnormalities in remnant lipoproteins may occur only with use of atorvastatin.
      Combination treatment with statin and fish oil may, however, offer an optimal
      therapeutic approach for globally correcting dyslipidaemia in obesity.

PMID- 12059990
TI  - Procion orange tracer dye technique vs. identification of intrafibrillar
      fibronectin in the assessment of sarcolemmal damage.
AB  - BACKGROUND: The use of Procion orange dye (POD) is one of the most widely
      accepted techniques to assess sarcolemmal damage. This phenomenon has been
      related to functional adaptation in skeletal muscles. The POD method includes
      intravenous injection of this colorant in vivo, enabling its identification
      inside those fibres with membrane leaks (fluorescence). However, the safety of
      the use of POD has not been proven. AIM: This study was designed to compare POD
      with a safer alternative, involving the identification of intracellular
      fibronectin using specific antibodies. METHOD: Eight Swiss mice were submitted to
      electrical stimulation of the lower limbs at different frequencies (10-80 Hz).
      Subsequently, the POD solution was infused, and samples from the vastus medialis
      muscle were obtained 24 h later. Samples were processed and serial sections were
      analysed using immunohistochemistry (monoclonal antibodies against fibronectin)
      and epifluorescence microscopy. RESULTS: Ninety-eight per cent of the fibres were
      equally classified by both techniques, which in addition showed good correlation
      (percentages of damaged fibres, r = 0.998, P < 0.001) and concordance (R1 = 0.82)
      in quantitative terms. CONCLUSIONS: Although the two techniques compared here are
      based on different principles, both are comparable in assessing sarcolemmal
      damage. This would facilitate comparisons between human and experimental studies.
      In addition, the fibronectin technique appears to be a suitable alternative for
      long-term studies including repeated biopsies.

PMID- 12059989
TI  - Tauroursodeoxycholic acid mobilizes alpha-PKC after uptake in human HepG2
      hepatoma cells.
AB  - BACKGROUND: Tauroursodeoxycholic acid (TUDCA) may exert anticholestatic effects
      via Ca(++)- and alpha-protein kinase C (alpha-PKC)-dependent apical vesicular
      insertion of canalicular transporters in cholestatic hepatocytes (Hepatology
      2001; 33: 1206-16). Tauroursodeoxycholic acid is mainly taken up into liver cells
      by Na(+)-taurocholate cotransporting polypeptide (Ntcp). Tauroursodeoxycholic
      acid selectively translocates alpha-PKC, a key mediator of regulated exocytosis,
      to hepatocellular membranes. It is unclear whether TUDCA exerts its effects on
      alpha-PKC after carrier-mediated uptake into liver cells or by interaction with
      extracellular/membraneous structures. MATERIALS AND METHODS: Human hepatoblastoma
      HepG2 cells lacking Ntcp were stably transfected with pcDNA3.1/Ntcp or sham
      transfected with pcDNA3.1 [+]. Distribution of alpha-PKC was studied using a
      Western blotting technique. Uptake of [(3)H]taurocholic acid (TCA) was determined
      radiochemically. RESULTS: [(3)H]taurocholic acid uptake was approximately 180
      fold higher in Ntcp-transfected than in sham-transfected cells. Phorbol 12
      myristate 13-acetate (1 micromol L(-1); positive control) increased membrane
      binding of alpha-PKC by 34% in Ntcp-transfected and by 37% in sham-transfected
      cells. Tauroursodeoxycholic acid (10 micromol L(-1)) increased membrane
      associated alpha-PKC by 19% in Ntcp-transfected, but not in sham-transfected
      cells (-13%). Taurocholic acid (10 micromol L(-1)) did not affect the
      distribution of alpha-PKC. CONCLUSION: Carrier-mediated uptake is a prerequisite
      for TUDCA-induced translocation of alpha-PKC to hepatocellular membranes.

PMID- 12059991
TI  - Molecular causes of colon cancer.
AB  - Cells in a developing embryo communicate with each other through a limited number
      of intercellular signalling pathways, of which the Wnt signalling pathway is one.
      Little is known about the function of Wnt signalling beyond that in
      embryogenesis. However, recent insights into the molecular etiology of colon
      cancer have implied a central role for the Wnt signalling pathway. The malignant
      transformation of colorectal epithelium is well defined, leading to adenoma and
      sequentially carcinoma formation. Several genes that regulate the Wnt pathway are
      mutated in cancer of the human colon and other organs. All of these mutations
      lead to the inappropriate activation of the pathway, which instructs the cell to
      divide unrestrictedly. These insights now allow the Wnt pathway to be exploited
      as a new target for drug development in colon cancer.

PMID- 12059995
TI  - The economic cost of epilepsy: a review of the literature.
AB  - Economic concerns are increasingly important in health system design, provider
      payment, and research funding decisions. Cost estimates are needed to provide
      insight into where the potential opportunities for cost-savings lie and to lay
      the groundwork for research to determine how to treat the disorder more
      effectively. The methods used by economists to estimate the direct and indirect
      costs of epilepsy are reviewed and results from studies in different countries
      are discussed. General patterns across patients with different types of
      conditions are reported. Gaps in the literature are identified and future
      research needs are assessed.

PMID- 12059992
TI  - Enhanced DNA damage-induced p53 peptide phosphorylation and cell-cycle arrest in
      Sjogren's syndrome cells.
AB  - BACKGROUND: Cells from primary Sjogren's syndrome (SS) patients have been
      reported to show alterations in DNA repair and p53 expression. The DNA-dependent
      protein kinase (DNA-PK) autoantigen may be involved in both of these alterations
      in relation to cellular DNA damage responses. We conducted this study of cell
      cycle kinetics and p53 to find additional evidence for an abnormal stress
      response role in the pathogenesis of SS. DESIGN: DNA-dependent protein kinase
      activity, p53 peptide phosphorylation and p53 protein levels were determined in
      gamma-irradiated long-term T lymphocyte cultures. Cell-cycle progression of
      peripheral blood mononuclear cells was analysed with flow cytometry. RESULTS: No
      significant differences in the DNA-PK activities or p53 protein levels appeared
      between the SS patients and the healthy individuals. However, patients with the
      SS hallmark Ro/SS-A and La/SS-B autoantibodies showed enhancement of both p53
      peptide phosphorylation (P = 0.036) and G1 cell-cycle arrest (P = 0.015) in
      response to gamma radiation. CONCLUSIONS: Sjogren's syndrome cells express an
      enhanced G1 checkpoint function which may be mediated partly by p53
      phosphorylation, suggesting that an abnormal stress response in SS is of
      relevance for the development of this autoimmune disease.

PMID- 12059997
TI  - Cost-effectiveness of epilepsy therapy: how should treatment effects be measured?
AB  - Economic evaluations aim to inform policy makers about the cost-effectiveness of
      different therapies so that limited health care resources may be allocated
      efficiently. For such evaluations, the effects of therapy must be captured by
      measures that are reliable, valid, and clinically meaningful. Mortality and
      changes in disease activity (e.g., seizure freedom, reduction in seizure
      frequency) may be reliable and valid, but their clinical meaning is not always
      apparent. Changes in widely used "quality-of-life" measures can quantify
      therapeutic effects, but the value of such changes to patients is not necessarily
      clear. This article reviews conceptual and methodological issues involved in
      determining the value of health effects in the context of economic evaluations of
      epilepsy therapies. Techniques for eliciting preferences for health effects are
      reviewed. The limited information on preferences for epilepsy-related health
      states is described. Directions for further research are suggested.

PMID- 12059996
TI  - Economic evaluation of epilepsy treatment: a review of the literature.
AB  - This article provides an overview of methods used and findings from economic
      analyses in epilepsy. Cost-effectiveness studies have evaluated different drugs
      for monotherapy and add-on therapy, and compared alternative treatment modalities
      for refractory epilepsy. The methodological characteristics of these studies are
      examined, and their results are compared and interpreted. Health outcome measures
      are defined and data sources described. Methods for assessing the direct and
      indirect costs, and/or cost savings, with a treatment's use, are explored.
      Directions for future research are identified and discussed.

PMID- 12059998
TI  - A comparison of surgical and medical costs for refractory epilepsy.

PMID- 12059999
TI  - Economics in epilepsy treatment choices: our certain fate?

PMID- 12060001
TI  - Neonatal seizures and syndromes.
AB  - Neonatal seizures frequently accompany neonatal encephalopathies. Seizures occur
      in approximately 1.8-5/1,000 live births in this country and are caused by
      virtually any condition that affects neonatal brain function. This review
      provides a simple classification of seizures and emphasizes that many abnormal
      intermittent behaviors in this age group are not accompanied by ictal EEG
      patterns. Additionally, < or =50% of neonatal seizures are not associated with
      abnormal clinical behavior. This is a common phenomenon, particularly after
      anticonvulsant treatment in which the clinical seizures are suppressed but
      electrographic seizures continue unabated. Seizures also may be caused by genetic
      disorders, several of which are benign, familial, and caused by channelopathies
      involving potassium channels. The review also discusses the epileptic syndromes
      seen in neonates, including early myoclonic encephalopathy, Ohtahara syndrome,
      pyridoxine dependency, and glucose transporter type 1 syndrome.

PMID- 12060002
TI  - Infantile seizures and epilepsy syndromes.
AB  - Despite difficulties in precisely identifying and classifying infantile seizures,
      most infantile epilepsy syndromes can be classified, at least in broad
      categories. Infants with intractable epilepsy, however, may be difficult to
      accurately classify. These patients have complex presentations that do not easily
      allow labeling into "focal" or "generalized" categories. Within each category of
      infantile epilepsy, there appear to be benign and severe forms. Classifications
      based on semiology may be easier to use for all infants with epilepsy. At least
      three broad categories of epilepsy can be identified: infants with myoclonic
      seizures, infants with spasms, and infants with focal seizures. Within each
      category benign and severe presentations exist, with clearly defined, unique
      features. Whether the various presentations of epilepsy in infants can be cleanly
      separated into these categories, or need to be considered as points along a
      biologic spectrum, will require further research.

PMID- 12060003
TI  - EEG in benign and malignant epileptic syndromes of childhood.
AB  - Characteristic appearances of epileptiform EEG activity in children aged between
      2 and 10 years are described. Emphasis is placed on the value of careful analysis
      of background EEG and how the epileptiform activity itself may overlap between
      benign and malignant epileptic syndromes. Illustrations are used to underscore
      this emphasis. Irrespective of how "classic" an EEG appearance is, accurate
      classification of a child's epileptic syndrome requires integration of all
      available clinical data. EEG is just one component of this equation.

PMID- 12060004
TI  - Epileptic syndromes in childhood: clinical features, outcomes, and treatment.
AB  - We reviewed the clinical features, outcome, and treatment of many of the
      epileptic syndromes that begin in the childhood from 2 to 12 years of age, using
      a review of the literature and personal experience, with most references to
      authoritative texts. The developmental tasks of childhood are centered on
      refinement of motor skills and development of complex intellectual and social
      skills. The childhood onset epilepsies can be divided into benign, intermediate,
      and catastrophic based on their impact on childhood development. The clearest
      benign epilepsy is benign rolandic epilepsy, which often does not require
      medication treatment. The definition of benign occipital epilepsy is still often
      vague. In the intermediate category, childhood absence epilepsy often has
      associated learning disorders and a poor social outcome. About 50% of children
      with cryptogenic partial seizures have a very benign course, even though their
      epilepsy syndrome is not well defined. Generalized epilepsy with febrile seizures
      plus (GEFS+) has a dominant inheritance with a defined defect in cerebral sodium
      channels, but varies considerably in severity within affected members of the same
      kindred. The catastrophic epilepsies in childhood all have an inconsistent
      response to AED treatment and include continuous spike-wave in slow sleep (with
      variable severity), Landau-Kleffner syndrome (with a confusing overlap with
      autistic regression), the Lennox Gastaut syndrome (with broad defining features),
      and myoclonic-astatic epilepsy (with important overlaps with Lennox-Gastaut).
      Many of the epilepsies that begin in childhood are benign. Others interfere
      seriously with cognitive and social development.

PMID- 12060005
TI  - Adolescent seizures and epilepsy syndromes.
AB  - Specific epilepsy syndromes begin during adolescence and create a significant
      neurologic burden. Knowledge of these syndromes has important treatment and
      prognostic implications, which usually extend into adulthood. Little is known
      about the effect of menarche on seizures, even though a relationship of seizures
      to the menstrual cycle has been observed for many years. In general, puberty is
      not thought to influence seizure frequency. However, estrogen is thought to
      activate epileptiform activity; testosterone may decrease seizure activity; and
      progesterone decreases epileptiform discharges. These effects are mediated by
      effecting gammaaminobutyric acid (GABA) transmission. Idiopathic generalized
      epilepsies are the most frequent group with adolescent onset. These are probably
      polygenic in origin and represent a biologic continuum. Juvenile myoclonic
      epilepsy (JME) is the most common form. This contrasts with a variety of
      progressive myoclonic epilepsies that also are first seen in adolescence and have
      a genetic origin and specific treatments. Finally, although temporal lobe
      epilepsy associated with hippocampal sclerosis may have its origin in childhood,
      often the child does not come to surgical evaluation until adolescence or young
      adulthood. The characteristic clinical history, seizure semiology, and magnetic
      resonance imaging findings have allowed a discrete epilepsy syndrome to be
      established. Applying these same criteria to children and adolescents reveals
      that hippocampal sclerosis is the most common lesion responsible for their
      intractable temporal lobe epilepsy. Hippocampal sclerosis is probably
      underdiagnosed in children. The safety and efficacy of epilepsy surgery in the
      age group is excellent. Knowledge of the epilepsy syndromes that remit before
      adolescence, may persist into adolescence, or begin in adolescence is central to
      the treatment of this age group.

PMID- 12060006
TI  - Children versus adults: pharmacokinetic and adverse-effect differences.
AB  - Pharmacokinetic differences may play a part in the age-related differences in the
      incidence of adverse effects. The most common idiosyncratic reaction to
      lamotrigine (LTG) is rash, affecting 10-20% of patients. Risk factors are young
      age, concurrent valproate (VPA), high starting dose, and rapid escalation. In
      children, cytochrome P450 (CYP)-catalyzed metabolism is increased, and uridine
      diphosphate (UDP)-glucuronosyltransferase (UGT)-catalyzed metabolism is not
      significantly different from that in adults. A CYP-catalyzed arene oxide
      intermediate of LTG has been identified. The increase CYP metabolism of LTG in
      children could result in increased formation of the reactive metabolite and a
      higher incident of rash. Children often received higher milligram per kilogram
      doses compared with adults. The higher dose would cause an increased amount of
      LTG metabolized to the reactive arene oxide intermediate. VPA therapy is
      associated with a transient elevation in liver-function tests in 15-30% of
      patients and a rare, fatal hepatotoxicity. Most cases of VPA hepatotoxicity
      occurred in children younger than 2 years who had preexisting neurologic or other
      physical defects. Hypotheses regarding the pathogenesis of the hepatotoxicity
      include preexisting mitochondrial disease or inborn errors of metabolism, VPA
      inhibition of beta-oxidation, and toxicity from VPA metabolites VPA, 4-ene-VPA,
      and 2,4-diene-VPA. Infants and children have higher concentration ratios of 4-ene
      VPA to VPA. Polytherapy with enzyme inducers increases the formation of the
      hepatotoxic metabolites. The role of underlying metabolic disorders associated
      with hepatodegeneration and intractable seizures without VPA is a major
      confounder in identifying risk factors and demonstrates the difficulty in
      separating underlying disease factors in rare idiosyncratic reactions.

PMID- 12060007
TI  - The spectrum of nonepileptic events in children.
AB  - Nonepileptic events (NEE) are common in children, and can be difficult to
      distinguish from epileptic events. Several strategies can assist in
      differentiation. The first is an age-based approach to the differential of
      commonly presenting EEs in neonates, infants, and adolescents. The next strategy
      is to identify key elements of the patient's history to narrow the possibilities,
      and third is a rational approach to ancillary testing. There are additional
      challenges to the diagnosis and evaluation of NEEs in patients with cognitive
      impairments or mental retardation (MR). Twenty to 25% of neurologically normal
      patients (34), and up to 60% of children with MR (35) referred for an evaluation
      of seizures, have NEE. In most instances, the clinical history leads to the
      diagnosis, and ancillary testing serves as confirmation. But in certain
      populations, neonates, children with concurrent epilepsy, children in whom
      pseudoseizures are suspected, and children with MR, early use of video-EEG
      telemetry is indicated to establish the diagnosis and avoid overtreatment with
      antiepileptic drugs (AEDs).

PMID- 12060009
TI  - What do you do when they grow up? Approaches to seizures in developmentally
      delayed adults.
AB  - Epilepsy and developmental disabilities (DD) often occur together but affect
      individuals differently and have a complex causal relationship. Most epilepsy in
      the population with DD is partial or symptomatic generalized. Seizures and
      antiepileptic drugs (AEDs) can further delay development, and the DD can
      complicate treatment and adjustment to epilepsy. Medical care and decision making
      require careful coordination of health care providers and the family, especially
      because of the trend for the patients to live in group homes. Behavioral and
      psychiatric disorders are difficult to diagnose but common in those with DD and
      epilepsy; psychiatric disorders are perhaps up to sevenfold higher in this group
      than in the general population. Psychotropic medications-antidepressants,
      anxiolytics (but use caution with benzodiazepines), antipsychotics, and
      stimulants-are appropriate for those with psychiatric disorders. Diagnostic
      difficulties may lead to undertreatment, and the motivation to lessen certain
      behaviors may lead to overtreatment. Because those with DD may be unusually
      sensitive to adverse effects of both seizures and AEDs, cognitive and behavioral
      side effects must be carefully monitored. Few relevant studies exist. For some
      patients, comorbid psychiatric disorders may be treated with one AED, such as
      carbamazepine, lamotrigine, or valproate. Phenobarbital and phenytoin may be
      inappropriate for those with epilepsy and DD. Studies have shown some success
      with oxcarbazepine (for partial and generalized epilepsy) and with adjunctive
      lamotrigine. For those on medication regimens, perhaps taking combinations of
      drugs for numerous years, queries about earlier attempts to reduce AEDs and
      gradual efforts to substitute less toxic mediations are worthwhile. Vagus nerve
      stimulation and epilepsy surgery for those with medically refractory epilepsy may
      be options after careful evaluation.

PMID- 12060008
TI  - Epilepsy surgery in childhood.
AB  - Epilepsy surgery in childhood can now be more readily considered as a result of
      enhanced presurgical investigative techniques and safer neurosurgical practice.
      As in adults, surgery available may be resective (focal resection or
      hemispherectomy) or functional. The most common procedures are temporal lobectomy
      and hemispherectomy, with malformative lesions and developmental tumours the next
      common pathology. The timing of surgery requires careful consideration, and the
      definition of drug resistance given specific thought in the young child.
      Presurgical evaluation should be noninvasive where possible, and should include
      optimised MRI, including 3D data set and video EEG telemetry to document
      seizures. Detection of temporal lobe abnormalities in temporal lobe epilepsy with
      MR may be enhanced using quantitative and semiquantitative techniques. Ictal and
      interictal SPECT may be useful in providing information about the seizure onset
      zone, if reviewed in conjunction with MR data and video-EEG. Interictal PET is
      more likely to demonstrate abnormalities relating to structural defects, but may
      be particularly useful in infants where incomplete myelination may restrict
      structural information provided by MRI. Neuropsychology testing plays a major
      role by the determination of verbal and nonverbal function in older children, and
      in the determination of cerebral dominance. Functional MRI for determination of
      language or motor cortex may enhance such evaluation, although it is limited to
      older unsedated children at present. Although the aims of the presurgical
      evaluation remain similar to adult practice, the range of children presenting is
      wide, and the aims and likely outcome of surgery require careful evaluation with
      the family. This aside, the benefits of seizure elimination or reduction in drug
      resistant focal epilepsy prior to adolescence, as well as in certain early
      catastrophic epilepsies of childhood, remain self apparent.

PMID- 12060010
TI  - Video-EEG monitoring in adults.
AB  - The routine EEG study may prove inadequate in selected patients with recurrent
      and unprovoked seizures. Video-EEG monitoring is an important diagnostic
      innovation that may be used to confirm the diagnosis of a seizure disorder and
      classify seizure type. The methodologies and clinical applications of video-EEG
      monitoring are reviewed. Long-term EEG recordings may be performed as an
      outpatient or in an epilepsy monitoring unit. Potential techniques for video-EEG
      monitoring include prolonged conventional routine EEG, ambulatory EEG, and
      computer-assisted EEG recordings. Periictal SPECT studies performed during long
      term EEG recordings in the epilepsy monitoring unit may increase the diagnostic
      yield of a presurgical evaluation. Video-EEG monitoring is essential for surgical
      localization in patients with intractable partial epilepsy being considered for a
      focal cortical resection. The studies may also be necessary to confirm the
      presence of nonepileptical clinical episodes.

PMID- 12060012
TI  - Is it status?
AB  - Nonconvulsive status epilepticus (NCSE) is difficult to diagnose in the
      obtunded/comatose patient. Such patients often have other serious medical
      conditions, and the diagnosis is frequently delayed. We review criteria for
      diagnosis, treatment, and prognosis of NCSE in this setting. Terms that have been
      used to describe SE in obtunded/comatose patients without tonic-clonic
      convulsions include subtle generalized SE, electrographic SE, SE in comatose
      patients, generalized electrographic SE, non-tonic-clonic SE, subclinical SE, and
      NCSE. Sometimes the same term has been used when describing different disorders,
      and different terms are often applied for the same entity. The incidence of NCSE
      in obtunded/comatose patients is uncertain. Clinically they may display subtle,
      intermittent focal or multifocal rhythmic movements suggestive of seizures; there
      may not be movements. NCSE can occur in a variety of disorders, including
      hypoxia, metabolic disturbances, and after convulsive seizures. A number of EEG
      patterns have been described in NCSE, and many of these are controversial,
      particularly as to whether they are ictal. These include periodic lateralized
      epileptiform discharges (PLEDS), bilateral independent PLEDS (BIPLEDS), periodic
      epileptiform discharges (PEDS), which can be either focal or generalized, and
      generalized triphasic waves (TWs). The diagnostic criteria for NCSE also are
      controversial, and there are no agreed-on criteria to diagnose NCSE in
      obtunded/comatose patients, nor is there consensus on how it should it be
      treated. Furthermore, outcome is poor, and several studies suggest that treatment
      may not be helpful.

PMID- 12060011
TI  - Epilepsy and EEG in the elderly.
AB  - Seizures are now the third most frequently encountered neurologic problem in the
      elderly population. The incidence of recurrent unprovoked seizures peaks in older
      patients. Because of this age-related increase and the growing elderly
      population, evaluation and treatment of the elderly patient has received
      increasing attention. This article focuses on epilepsy, not acute seizures in the
      elderly. The causes and types of epilepsy older individuals experience are
      reviewed, along with the diagnostic role of EEG. Treatment options are briefly
      addressed.

PMID- 12060013
TI  - Continuous EEG monitoring in the intensive care unit.
AB  - Continuous EEG (CEEG) monitoring allows uninterrupted assessment of cerebral
      cortical activity with good spatial resolution and excellent temporal resolution.
      Thus, this procedure provides a means of constantly assessing brain function in
      critically ill obtunded and comatose patients. Recent advances in digital EEG
      acquisition, storage, quantitative analysis, and transmission have made CEEG
      monitoring in the intensive care unit (ICU) technically feasible and useful. This
      article summarizes the indications and methodology of CEEG monitoring in the ICU,
      and discusses the role of some quantitative EEG analysis techniques in near real
      time remote observation of CEEG recordings. Clinical examples of CEEG use,
      including monitoring of status epilepticus, assessment of ongoing therapy for
      treatment of seizures in critically ill patients, and monitoring for cerebral
      ischemia, are presented. Areas requiring further development of CEEG monitoring
      techniques and indications are discussed.

PMID- 12060014
TI  - Pentylenetetrazol-induced recurrent seizures in rat pups: time course on spatial
      learning and long-term effects.
AB  - PURPOSE: Recurrent seizures in infants are associated with a high incidence of
      neurocognitive deficits. Animal models have suggested that the immature brain is
      less vulnerable to seizure-induced injury than is that in adult animals. We
      studied the effects of recurrent neonatal seizures on cognitive tasks performed
      when the animals were in adolescence and adulthood. METHODS: Seizures were
      induced by intraperitoneal injection of pentylenetetrazol (PTZ) for 5 consecutive
      days, starting from postnatal day 10 (P10). At P35 and P60, rats were tested for
      spatial memory by using the Morris water maze task. In adulthood, motor
      performance was examined by the Rotarod test, and activity level was assessed by
      the open field test. Seizure threshold was examined by inhalant flurothyl. To
      assess presence or absence of spontaneous seizures, rats were video recorded for
      4 h/day for 10 consecutive days for the detection of spontaneous seizures.
      Finally, brains were examined for histologic evidence of injury with cresyl
      violet stain and Timm staining in the supragranular zone and CA3 pyramidal cell
      layers of the hippocampus. RESULTS: PTZ-treated rats showed significant spatial
      deficits in the Morris water maze at both P35 and P60. There were no differences
      in seizure threshold, motor balance, or activity level during the open field
      test. Spontaneous seizures were not recorded in any rat. The cresyl violet stain
      showed no cell loss in either the control or experimental rats. PTZ-treated rats
      exhibited more Timm staining in the CA3 subfield. However, the control and
      experimental rats showed similar Timm staining within the supragranular zone.
      CONCLUSIONS: Our findings indicate that recurrent PTZ-induced seizures result in
      long-term cognitive deficits and morphologic changes in the developing brain.
      Furthermore, these cognitive deficits could be detected during pubescence.

PMID- 12060015
TI  - Cooling abolishes neuronal network synchronization in rat hippocampal slices.
AB  - PURPOSE: We sought to determine whether cooling brain tissue from 34 to 21
      degrees C could abolish tetany-induced neuronal network synchronization (gamma
      oscillations) without blocking normal synaptic transmission. METHODS:
      Intracellular and extracellular electrodes recorded activity in transverse
      hippocampal slices (450-500 microm) from Sprague-Dawley male rats, maintained in
      an air-fluid interface chamber. Gamma oscillations were evoked by afferent
      stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber
      was 34 degrees C, reduced to 21 degrees C within 20 min. RESULTS: Suprathreshold
      tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency
      range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by
      bicuculline, a gamma-aminobutyric acid (GABA)A-receptor antagonist. Cooling from
      34 to 21 degrees C reversibly abolished gamma oscillations in all slices tested.
      Short, low-frequency discharges persisted after cooling in six of 14 slices.
      Single-pulse-evoked potentials, however, were preserved after cooling in all
      cases. Latency between stimulus and onset of gamma oscillation was increased with
      cooling. Frequency of oscillation was correlated with chamber cooling temperature
      (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma
      oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma
      oscillation and abolished epileptiform bursts in a reversible manner.
      CONCLUSIONS: Tetany-induced neuronal network synchronization by GABAA-sensitive
      gamma oscillations is abolished reversibly by cooling to temperatures that do not
      block excitatory synaptic transmission. Cooling also suppresses transition from
      gamma oscillation to ictal bursting at higher stimulus intensities. These
      findings suggest that cooling may disrupt network synchrony necessary for
      epileptiform activity.

PMID- 12060016
TI  - Clinical and genetic analysis of a new multigenerational pedigree with GEFS+
      (Generalized Epilepsy with Febrile Seizures Plus).
AB  - Febrile seizures affect 2-5% of all children younger than 6 years. A small
      proportion of children with febrile seizures later develop epilepsy. The syndrome
      of generalized epilepsy with febrile seizures plus (GEFS+) is a heterogeneous
      disorder characterized by febrile seizures that may persist beyond age 6 years
      and nonfebrile seizures. Several genes have been localized for FS by linkage
      analysis, and three GEFS+ genes (SCN1A, SCN1B, GABRG2) have been identified. We
      identified a large multigenerational family with GEFS+ in France. All affected
      members had FSs. Among them, seven had other types of epileptic seizures
      including FSs after age 6 years, nonfebrile generalized seizures, or partial
      seizures later in life. Genetic linkage study excluded the candidate genes and
      loci for FS and GEFS+, thus proving the existence of a new GEFS+ genetic locus
      underlying the phenotype observed in this family.

PMID- 12060017
TI  - The effectiveness of cognitive rehabilitation for attention deficits in focal
      seizures: a randomized controlled study.
AB  - PURPOSE: Cognitive deficits are one of the major limiting factors in the everyday
      life functioning of patients with focal seizures. Although cognitive
      rehabilitation methods have been successfully applied to patients with other
      central nervous system (CNS) lesions, these methods have not yet been evaluated
      in cognitively impaired patients with epilepsy. The present study evaluated the
      effectiveness of two commonly used methods for attention deficits: (a) the
      Retraining Method, aimed at retraining impaired cognitive functions; and (b) the
      Compensation Method, aimed at teaching compensatory strategies while taking
      neuronal loss for granted. METHODS: Fifty adult outpatients with focal seizures
      and attention impairments receiving carbamazepine (CBZ) monotherapy were randomly
      assigned to the Retraining Method, the Compensation Method, or to a waiting-list
      control group. Established and self-reported neuropsychological outcomes and self
      reported quality of life of these groups were evaluated at pretraining,
      posttraining, and at a 6-month follow-up measurement point and were completed by
      44 patients. RESULTS: Neuropsychological outcomes related to training, self
      reported neuropsychological outcomes, and quality of life at the 6-month follow
      up measurement point improved both in the Retraining Method group (n = 19) and
      the Compensation Method group (n = 17) relative to the waiting-list control group
      (n = 8). The Compensation Method was more effective in improving self-reported
      neuropsychological outcomes and quality of life, especially for patients with
      less education. The patients with active epilepsy benefited more from both
      methods than did the seizure-free patients. CONCLUSIONS: These data show that
      cognitive rehabilitation programs are effective for patients with focal seizures
      and attention deficits and should, therefore, be incorporated into comprehensive
      care programs.

PMID- 12060018
TI  - Detection and localization of focal cortical dysplasia by voxel-based 3-D MRI
      analysis.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is a frequent cause of partial epilepsy.
      Its diagnosis by visual evaluation of magnetic resonance images (MRIs) remains
      difficult. The purpose of this study was to apply a novel automated and observer
      independent voxel-based technique for the analysis of 3-dimensional (3-D) MRI to
      detect and localize FCD. METHODS: The technique was based on algorithms of the
      SPM99 software and included the spatial normalization of 3-D MRI data sets to a
      common stereotaxic space and the segmentation of cortical grey matter. The
      resulting data sets represented grey-matter density maps where each voxel encoded
      the grey-matter concentration at the corresponding position in the original MRI.
      A normal database was set up by calculating and averaging the grey-matter density
      maps of 30 healthy volunteers. The MRI data sets of seven epilepsy patients with
      FCD were evaluated retrospectively for dysplastic lesions by voxelwise
      subtraction of the mean grey-matter density map of the normal database and
      searching automatically for local and global maxima in the resulting data set.
      RESULTS: In all patients, the results of voxel-based 3-D MRI analysis
      corresponded both to the location of the dysplastic lesions in conventional MRI
      and to seizure semiology and EEG findings. In one case, surgery was performed,
      and the diagnosis FCD was supported by histology. CONCLUSIONS: The technique of
      voxel-based 3-D MRI analysis and comparison with a normal database seems to
      provide a valuable additional screening tool for the detection of FCD.

PMID- 12060019
TI  - Chronic anterior thalamus stimulation for intractable epilepsy.
AB  - PURPOSE: A significant number of patients with epilepsy remain poorly controlled
      despite antiepileptic medication (AED) treatment and are not eligible for
      resective surgery. Novel therapeutic methods are required to decrease seizure
      burden in this population. Several observations have indicated that the anterior
      thalamic region plays an important role in the maintenance and propagation of
      seizures. We investigated neuromodulation of the anterior thalamus by using deep
      brain stimulation (DBS) in patients with intractable seizures. METHODS: Five
      patients with medically refractory epilepsy underwent stereotactic placement of
      and received stimulation through bilateral DBS electrodes in the anterior
      thalamus. RESULTS: Treatment showed a statistically significant decrease in
      seizure frequency, with a mean reduction of 54% (mean follow-up, 15 months). Two
      of the patients had a seizure reduction of > or =75%. No adverse effects were
      observed after DBS electrode insertion or stimulation. Unexpectedly, the observed
      benefits did not differ between stimulation-on and stimulation-off periods.
      CONCLUSIONS: DBS of the anterior thalamus is a safe procedure and possibly
      effective in patients with medically resistant seizures.

PMID- 12060020
TI  - Different neurophysiologic patterns of myoclonus characterize Lennox-Gastaut
      syndrome and myoclonic astatic epilepsy.
AB  - PURPOSE: To study the neurophysiologic characteristics of epileptic myoclonus in
      patients with Lennox-Gastaut syndrome (LGS) and myoclonic astatic epilepsy (MAE).
      METHODS: Three patients with symptomatic LGS (mean age, 15 years +/- 4) and three
      with cryptogenic MAE (mean age, 9 years +/- 3) were studied. Temporal
      relationships between electroencephalographic (EEG) and electromyographic
      activity were studied by analyzing latencies of EEG activity related to the onset
      of single myoclonic jerks, by using burst-locked EEG averaging where necessary.
      RESULTS: LGS: neurophysiologic analysis indicated that jerks and the accompanying
      premyoclonic spikes showed latency differences between sides (mean +/- SD, 18 +/-
      5 ms for both) with a constant leading side in each patient. The premyoclonic
      spike latency was 20 +/- 10 ms (mean +/- SD). Topographic voltage mapping of the
      premyoclonic spike peak showed a unilateral frontal distribution. MAE: muscles
      from both sides were activated synchronously, and the EEG correlate was a
      generalized spike-wave, in which the negative peak of the spike preceded the
      generalized jerks by 30 +/- 2 ms (mean +/- SD). Topographic voltage mapping of
      the premyoclonic spike peak showed a diffuse distribution of the electrical
      field, predominating over the anterior regions, but not lateralized. CONCLUSIONS:
      These neurophysiologic findings indicate that epileptic myoclonus in LGS
      originates from a stable generator in the frontal cortex, to spread to
      contralateral and ipsilateral cortical areas, whereas myoclonus in MAE appears to
      be a primary generalized epileptic phenomenon.

PMID- 12060022
TI  - Clinical and electrographic features of epileptic spasms persisting beyond the
      second year of life.
AB  - PURPOSE: Few reports detailing the electroclinical features of epileptic spasms
      persisting beyond infancy have been published. We sought to characterize this
      unique population further. METHODS: We retrospectively reviewed the clinical and
      video-EEG data on 26 patients (4-17 years; mean, 93 months) with a confirmed
      diagnosis of epileptic spasms and who were evaluated at our tertiary referral
      center between 1993 and 2000. RESULTS: In half of our cases, epileptic spasms
      were associated with disorders of neuronal migration, severe perinatal asphyxia,
      and genetic anomalies. Interictal EEGs showed generalized slowing in the majority
      of patients, and a slow-wave transient followed by an attenuation of the
      background amplitude was the most common ictal EEG pattern associated with an
      epileptic spasm (19 cases). Other seizure types (number of cases in parentheses)
      included tonic seizures with or without a preceding spasm (13), partial seizures
      (11), myoclonic seizures (11), generalized tonic-clonic seizures (six), atypical
      absence seizures (two), and atonic seizures (one). Cases with a more organized
      EEG background (especially with frequencies > or =7 Hz) were more likely to have
      better cognition. Continued disorganization of the EEG background and persistence
      of hypsarrhythmia were associated with poor developmental outcome. CONCLUSIONS:
      Patients with epileptic spasms persisting beyond age 2 years constitute a truly
      refractory population, one that should be better recognized by clinicians.
      Interestingly, although many therapies resulted in a >50% reduction in seizures,
      neither neurocognitive function nor quality of life was substantially improved
      with intervention. The interictal EEG background is the most helpful in
      predicting neurologic outcome.

PMID- 12060021
TI  - Early-onset cobalamin C/D deficiency: epilepsy and electroencephalographic
      features.
AB  - PURPOSE: To describe epilepsy and EEG findings in the early-onset cobalamin (Cbl)
      C/D deficiency, an inborn error of intracellular Cbl metabolism characterized by
      high plasma levels of methylmalonic acid, homocystine, and homocysteine. METHODS:
      Type and frequency of seizures were studied in 10 patients (six boys and four
      girls) who underwent waking and sleep EEG. RESULTS: Half of patients had seizures
      in the first year of life (either concurrent with the other symptoms of disease
      or some months after the onset of disease); seizures occurred after 2 years in
      the other half of patients. Convulsive status epilepticus was the initial
      manifestation in three patients. During the follow-up, nine patients had seizures
      (mainly partial) despite specific treatment for Cbl C/D deficiency and
      antiepileptic drugs. Focal or multifocal epileptiform abnormalities during waking
      EEG that increased during sleep EEG were recorded in the majority of patients.
      Plasma levels of homocystine and homocysteine were constantly higher than normal,
      despite therapy institution. CONCLUSIONS: Epilepsy and EEG abnormalities are
      prominent features in the early-onset type of combined methylmalonic aciduria and
      homocystinuria due to Cbl C/D deficiency, possibly related to the pathologically
      and persistently high levels of homocysteine, experimentally proven to induce
      seizures. Plasma amino acids evaluation and urinary acid organic analysis should
      be performed in any infant showing seizures associated with feeding difficulties
      and failure to thrive, at onset during the first year of life, as well as in any
      child with convulsive status epilepticus and a history of psychomotor
      developmental delay of unknown origin.

PMID- 12060023
TI  - Cognitive skills in children with intractable epilepsy: comparison of surgical
      and nonsurgical candidates.
AB  - PURPOSE: To compare neuropsychological performance of two groups of children with
      intractable epilepsy: those who are surgical candidates, and those who are not.
      METHODS: Intelligence, verbal memory, visual memory, academic skills, and
      sustained attention were measured in children aged 6-18 years. The effects of
      number of antiepileptic drugs (AEDs), seizure frequency, age at seizure onset,
      and duration of seizure disorder were examined. RESULTS: Both groups had high
      rates of impairment. Group differences were found only on the verbal memory task.
      Children who experienced seizures in clusters had higher IQ, reading
      comprehension, and arithmetic scores. Age at seizure onset and proportion of life
      with seizures were related to IQ. Performance did not vary with AED monotherapy
      versus polytherapy. CONCLUSIONS: Few differences exist in cognitive performance
      between children with intractable seizures who are and those who are not surgical
      candidates. These findings suggest that children who are not surgical candidates
      can serve as good controls in studies on cognitive outcome of surgery.

PMID- 12060024
TI  - The effect of age on seizure semiology in childhood temporal lobe epilepsy.
AB  - PURPOSE: Complex partial seizure is the characteristic seizure type observed in
      epilepsy arising from temporal lobe structures. The seizure evolution in adult
      patients is quite stereotyped and well characterized, manifesting initially with
      an aura, behavioral arrest, and oroalimentary and gestural automatism. A greater
      variability of semiology including motor features with tonic or myoclonic
      components, as well as a paucity of automatism, has been reported in young
      children with temporal lobe epilepsy. The aim of our study was to examine in more
      detail the effects of age on individual ictal features to be able to determine
      the critical age when lesional temporal lobe seizure semiology undergoes
      transition from the pediatric to the more adult-type clinical pattern. METHODS:
      We performed a video analysis of 83 seizures from 15 children (aged 11-70 months)
      selected by post-temporal lobectomy seizure-free outcome, looking specifically at
      the motor and behavioral (nonmotor) manifestations in relation to age of the
      children. RESULTS: All of the children younger than 42 months had seizures with
      early and marked motor features, which included tonic and myoclonic components
      and epileptic spasms. Parallel with age, the frequency of these motor components
      decreased, and in five of 11 children older than 3 years, motor features were
      totally absent. Analyzed quantitatively, we saw a linear and inverse correlation
      of the ratio of motor components with age at monitoring. CONCLUSIONS: These
      findings support the hypothesis that events in brain maturation significantly
      affect clinical seizure semiology and may override the more typical localizing
      features seen in adult-type temporal lobe epilepsy. These findings are important
      to consider in the early diagnosis of childhood temporal lobe epilepsy.

PMID- 12060025
TI  - Risk factors for suicide in epilepsy: a case control study.
AB  - PURPOSE: Suicide is considered to be one of the most important causes of death
      contributing to the increased mortality of persons with epilepsy. We investigated
      the association between the risk of suicide in persons with epilepsy and clinical
      factors that might increase or have been suggested to increase the risk of
      suicide. METHODS: A case-control study was nested within a cohort of 6,880
      patients registered in the Stockholm County In-Patient Register with a diagnosis
      of epilepsy. The study population was followed up through the National Cause of
      Death Register. Twenty-six cases of suicide, 23 cases of suspected but not proven
      suicide, and 171 controls, living epilepsy patients, were selected from the
      cohort. Clinical data were collected through medical record review. RESULTS:
      There was a ninefold increase in risk of suicide with mental illness and a 10
      fold increase in relative risk (RR) with the use of antipsychotic drugs. The
      estimated RR of suicide was 16.0 [95% confidence interval (CI), 4.4-58.3] for
      onset of epilepsy at younger than 18 years, compared with onset after 29 years.
      The risk of suicide seemed to increase with high seizure frequency and
      antiepileptic drug (AED) polytherapy, although the estimates were imprecise and
      the associations not statistically significant. Insufficient data on seizure
      frequency and changes in AED dosage due to incomplete case records were
      associated with high RRs. We found no association between risk of suicide and any
      particular AED, with type of epilepsy, or localization or lateralization of
      epileptogenic focus on EEG [RR = 0.3 (95% CI, 0.1-1.7)]. CONCLUSIONS: The profile
      of the epilepsy patient who commits suicide that emerges from our study is a
      patient with early onset (particularly onset during adolescence) but not
      necessarily severe epilepsy, psychiatric illness, and perhaps inadequate
      neurologic follow-up. Previous reports of an association with temporal lobe
      epilepsy could not be confirmed.

PMID- 12060026
TI  - An epilepsy questionnaire study of knowledge and attitudes in Canadian college
      students.
AB  - PURPOSE: Controversy exists about the relation of societal knowledge and
      attitudes regarding epilepsy. We conducted a survey to examine knowledge and
      attitudes, to note gender and occupational influences, and to examine the effect
      of an informational brochure. METHODS: We administered a standardized
      questionnaire that noted demographics and examined knowledge and attitudes
      regarding epilepsy and persons with epilepsy, respectively, to a wide variety of
      Canadian college students. In a separate class we gave every other student a
      brochure regarding epilepsy and then administered the questionnaire to both the
      naive and brochure-exposed students. RESULTS: Knowledge was patchy and weakest
      for the approximate prevalence of epilepsy in the population, hereditary epilepsy
      and several other etiologies, recognition of nonconvulsive seizures as a type of
      epilepsy, and knowledge of antiepileptic drug-induced teratogenicity. In
      contrast, attitudes were more uniformly favorable. However, 11 and 14%,
      respectively, showed negative bias against persons with epilepsy having children
      and equal opportunity for occupational employment. Women were slightly but
      significantly more tolerant than men. The brochure-exposed group showed better
      knowledge but equivalent attitudes compared with the naive group. CONCLUSIONS:
      Results compare favorably with surveys in other countries. Although knowledge was
      patchy, it could be easily improved on with an educational brochure. Attitudes
      were positive but show some discrepancies from knowledge and a gender effect.

PMID- 12060027
TI  - The effect of age on rate of functional recovery after intracarotid amobarbital
      injection.
AB  - PURPOSE: The duration of the drug effect during the intracarotid amobarbital
      procedure (IAP) is an important factor when considering the prioritization of
      behavioral testing during the IAP. Previous studies of thiopental, a barbiturate
      similar to sodium amobarbital, found that age and gender significantly affect the
      dose required to induce anesthesia, such that younger patients require higher
      dosage. METHODS: A total of 55 patients who underwent the IAP procedure at Johns
      Hopkins Hospital were included in the study (110 hemispheric injections). The
      patient group included 30 female and 25 male patients, ranging in age from 11 to
      50 years. To determine if a higher dose of sodium amobarbital was needed for
      younger patients during the IAP, we analyzed the time to return to preinjection
      EEG baseline status and time to return to 5/5 strength as a function of patient
      age and gender. RESULTS: We found that younger patients (11-20 years old)
      returned to preinjection baseline EEG status and full (5/5) strength faster than
      older patients. No gender difference was found. CONCLUSIONS: The sodium
      amobarbital effect during IAP dissipates faster in young patients. Consideration
      of this difference in rate of recovery in 11-to 20-year-old patients has
      important clinical implications in terms of prioritizing behavioral testing.

PMID- 12060028
TI  - Long-term outcome is unchanged by antiepileptic drug treatment after a first
      seizure: a 15-year follow-up from a randomized trial in childhood.
AB  - PURPOSE: In 1989 we reported that 1 year of daily treatment with carbamazepine
      (CBZ) significantly reduced the recurrence rate after a first afebrile seizure in
      children compared with no treatment in a randomized open trial. We sought to
      determine if the long-term clinical course and rate of remission were changed by
      treatment starting after the first seizure. METHODS: Participants of the original
      trial (14 CBZ, 17 no medication) were contacted in 2001. RESULTS: Sixteen
      controls and 10 CBZ (84%) cases were followed up for 15 years. After
      randomization and follow-up, 12 controls and five treated patients had at least
      one more seizure (p = NS). For those with recurrences, the number of recurrences
      appeared to be the same in both groups. Number of medications used was also the
      same. Terminal remission (>2 years seizure free with or without medication) was
      achieved by eight (80%) of 10 CBZ and 14 (88%) of 16 controls, and terminal
      remission off medication in six (60%) of 10 CBZ (p = NS). CONCLUSIONS: Based on
      this small study with long follow-up, it appears that for children treated with
      CBZ after a first seizure, the subsequent clinical course and remission rates are
      not improved in comparison with a no-treatment strategy. Delaying treatment after
      a first seizure appears defensible.

PMID- 12060029
TI  - Postictal psychosis induced by temporal lobe seizures.

PMID- 12060030
TI  - Response: postictal psychosis induced by temporal lobe seizures.

PMID- 12060031
TI  - Interictal spikes: signs of a negative-feedback mechanism of epilepsy?

PMID- 12060033
TI  - ILAF report on classification and terminology.

PMID- 12060032
TI  - The tooth-losing dream and the epileptic state.

PMID- 12060034
TI  - ILAE Commission on the Burden of Epilepsy, Subcommission on the Economic Burden
      of Epilepsy: Final report 1998-2001.

PMID- 12060035
TI  - Barrett's esophagus: so what!

PMID- 12060036
TI  - Barrett's esophagus: what is the poison - alkaline, biliary or acidic reflux?

PMID- 12060037
TI  - Immunohistochemical presentation in non-malignant and malignant Barrett's
      epithelium.
AB  - Barrett's esophagus, which is histologically characterized by metaplastic
      columnar epithelium, is a common condition observed in approximately 10-20% of
      patients with gastroesophageal reflux disease. These lesions can typically
      progress from metaplasia with atypia to low-grade dysplasia, high-grade
      dysplasia, and adenocarcinoma. It is of great clinical importance to correctly
      grade these lesions and to identify changes with a high risk of malignant
      transformation, inasmuch as high-grade dysplasias and early adenocarcinomas in
      patients with Barrett's esophagus have a high chance for cure. The identification
      of high-risk lesions in Barrett's esophagus by histologic evaluation has
      drawbacks, especially regarding sampling errors and frequent intra- and
      interobserver discrepancies in the histopathologic grading/staging of these
      lesions. Immunostaining with a variety of antibodies provides a better
      understanding of the process of malignant transformation and helps to identify
      early markers of malignant transformation in Barrett's esophagus lesions. In this
      review, we will summarize the current knowledge about the value of immunostaining
      in the diagnosis of malignant and non-malignant Barrett's epithelium and its role
      to better define lesions with high risk for malignancy in this disorder.

PMID- 12060038
TI  - Angiogenic markers, neovascularization and malignant deformation of Barrett's
      esophagus.
AB  - The molecular events underlying progression of Barrett's esophagus to
      adenocarcinoma remain an area of active investigation. Neovascularization and
      angiogenesis have been studied in esophageal adenocarcinomas by counting of
      microvessels after staining with vascular markers, and by immunohistochemistry
      for vascular endothelial growth factor. Angiogenesis appears to be increased
      early in the neoplastic process, but has poor prognostic value. We have
      demonstrated that expression levels of two important genes that regulate cell
      growth, namely inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2,
      are frequently upregulated in Barrett's esophagus and associated adenocarcinomas.
      COX-2 expression may be related to reflux of bile salts, which induce COX-2
      expression in Barrett's tissues and esophageal adenocarcinoma cells in vitro. COX
      2 inhibition induces apoptosis and blocks proliferation in COX-2-expressing
      esophageal adenocarcinoma cells in vitro, and blocks angiogenesis in both in vivo
      and in vitro models. Although controversial, recent evidence suggest that iNOS
      derived NO can inhibit angiogenesis in some model systems. In conclusion, both
      iNOS and COX-2 appear to be involved in Barrett's-associated neoplastic
      progression, but COX-2 inhibition is more promising as a chemopreventive
      strategy. COX-2 inhibition may exert beneficial effects by decreasing
      angiogenesis and epithelial proliferation, and by facilitating apoptosis of
      epithelial cells that have undergone DNA damage.

PMID- 12060039
TI  - Mucosal ablation in Barrett's esophagus.
AB  - Barrett's esophagus is a prevalent, premalignant condition affecting the
      gastroesophageal junction and distal esophagus. Ablation plus antireflux therapy
      has recently been advocated to prevent the development of adenocarcinoma or to
      treat those unfit or unwilling to undergo esophagectomy. The present article,
      based on a search of Medline/ISI databases and cross-referencing of relevant
      articles, reviews the literature on this subject. A number of techniques have
      been used to remove the affected mucosa, including laser, electrocoagulation,
      argon plasma coagulation and photodynamic therapy but, as yet, none has been
      shown to be superior. Depending on the method used, ablation results in complete
      removal of Barrett's esophagus in approximately one third of patients and a
      partial response in nearly two-thirds. The resultant squamous mucosa is
      apparently 'normal' but may regress. To promote and maintain regeneration,
      antireflux therapy must be sufficient to reduce repetitive injury to the
      esophageal mucosa. Whether ablation reduces the cancer risk or delays its
      occurrence is unknown, though recent data suggests benefit. Complications are
      infrequent and usually mild. Regular follow-up endoscopy and deep biopsies
      continue to be necessary. Careful data from much larger populations with long
      term follow-up is required before ablation reaches the stage of broad clinical
      application.

PMID- 12060040
TI  - Ablation of Barrett's epithelium: the promise and the problems.
AB  - The incidence of adenocarcinoma of the esophagus has increased dramatically over
      recent years. Because Barrett's epithelium is recognized as a risk factor for
      adenocarcinoma there is an interest in reversing this metaplasia. A number of
      endoscopic methods of destruction of esophageal columnar epithelium have been
      described. The purpose of this article is to review the currently available
      methods of managing Barrett's epithelium with particular reference to the role of
      ablative therapy in reducing the risk of adenocarcinoma.

PMID- 12060041
TI  - Reasons for current practices in managing Barrett's esophagus.
AB  - We evaluated the reasons for current practices in managing Barrett's esophagus.
      Using a questionnaire, we assessed the practices and beliefs of 162 Californian
      gastroenterologists in managing Barrett's esophagus, using descriptive statistics
      as well as multivariate logistic regression. Out of the 103 respondents, 87%
      screened for Barrett's esophagus in patients with > 12 months of reflux symptoms,
      but only 72% believed that screening would improve survival, and 48% believed it
      to be cost-effective. In total, 98% surveyed patients with long-segment Barrett's
      esophagus at least biennially (76% thought this would improve survival and 49%
      believed it to be cost-effective) and 82% surveyed short-segment Barrett's
      esophagus at least biennially (57% thought this would improve survival and 30%
      believed it to be cost-effective). Finally, 44% surveyed microscopic intestinal
      metaplasia at least biennially (26% thought this would improve survival and 11%
      believed it to be cost-effective). In total, 18% performed endoscopic ablation,
      whereas 3% referred patients with low-grade dysplasia and 85% referred patients
      with high-grade dysplasia for esophagectomy. Finally, 81% treated asymptomatic
      Barrett's esophagus patients with proton pump inhibitors, but only 56% believed
      that this would reduce the risk of cancer. Logistic regression showed that the
      only independent factor predictive of surveillance practices was belief in
      efficacy. Practice patterns tend to be more aggressive than those recommended by
      recent guidelines and those reported by previous surveys. Medico-legal
      considerations affect practice substantially.

PMID- 12060042
TI  - Perception of esophageal manometry.
AB  - Esophageal manometry is an important investigation method but its direct impact
      on patients' well-being has not been studied. A structured questionnaire was
      given to all patients (n=92) after the manometry during one calendar year. The
      response rate was 91%. A total of seventy-one patients also reported their health
      status during the next 24 h. No serious side-effects were recorded. About half of
      the respondents regarded manometry as an easy or fairly easy investigation. The
      most common problems were irritation of nose and throat. In total, 48% of the
      respondents had mild to moderate late symptoms after manometry, usually soreness
      of the throat or nose lasting for some hours. The manometry was more troublesome
      to women than to men. It is concluded that esophageal manometry is generally a
      benign and fairly tolerated investigation, and the high level of anxiety that
      many patients show before the manometry is not well justified.

PMID- 12060043
TI  - Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of
      reflux esophagitis and the influence of Helicobacter pylori infection on healing
      rate.
AB  - Patients with reflux esophagitis (grade II or III, Savary-Miller, intention-to
      treat, n=256, age range 19-82 years) were randomly assigned to a double-blind,
      double-dummy treatment with either pantoprazole 40 mg once daily or ranitidine
      150 mg twice daily. After 4 weeks, each patient was clinically and endoscopically
      assessed. Failure to heal required a further 4 weeks of treatment and a new
      evaluation thereafter. After 4 weeks, healing of lesions was confirmed in 63% (69
      out of 109) of patients receiving pantoprazole and in 22% (25 out of 113)
      receiving ranitidine (P < 0.001, per protocol population). After 8 weeks, the
      cumulative healing rates were 88% and 46%, respectively (P < 0.001). Complete
      freedom from esophagitis-related symptoms (acid eructation, heartburn, pain while
      swallowing) was greater in the pantoprazole than in ranitidine group after 2 and
      4 weeks (74% vs. 47%; 87% vs. 52%, respectively, P < 0.001). After 4 weeks, the
      healing rate was 76% in Helicobacter pylori (Hp)-positive vs. 45% in Hp-negative
      patients treated with pantoprazole (P < 0.01). The Hp status did not influence
      healing rates in patients treated with ranitidine. The most frequent adverse
      events in the pantoprazole group were diarrhea and somnolence (2-3% of patients),
      and in the ranitidine group, headache, diarrhea, dizziness, increase of liver
      enzymes and pruritus (2-4% of patients). In conclusion, pantoprazole was more
      effective than ranitidine in the healing rate and relief from reflux esophagitis
      associated symptoms, and Hp infection was associated with higher healing rate
      during therapy with pantoprazole but not with ranitidine.

PMID- 12060044
TI  - Preoperative esophageal body motility does not influence the outcome of
      laparoscopic Nissen fundoplication for gastroesophageal reflux disease.
AB  - We evaluated a policy of performing laparoscopic antireflux surgery without
      tailoring the procedure to the results of preoperative esophageal motility tests.
      A total of 117 patients (82 with normal esophageal motility; 35 with ineffective
      motility, IEM) underwent laparoscopic Nissen fundoplication for symptomatic
      gastroesophageal reflux. There were no significant differences in preoperative
      symptom length, dysphagia, DeMeester symptom scores, acid exposure times or lower
      esophageal sphincter pressures between the two groups. Both groups showed
      postoperative improvements in DeMeester symptom scores, dysphagia and acid
      exposure, with no differences between groups. At 1 year after surgery, 95% of the
      normal motility group and 91% of the IEM group had a good/excellent outcome from
      surgery. None of the IEM group required postoperative dilatation or reoperation.
      Patients with IEM fare equally well from laparoscopic Nissen fundoplication as
      those with normal esophageal motility. There is no merit in tailoring antireflux
      surgery to the results of preoperative motility tests.

PMID- 12060045
TI  - Histopathologic effects of neoadjuvant therapies for advanced squamous cell
      carcinoma of the esophagus: multivariate analysis of predictive factors and p53
      overexpression.
AB  - In 97 patients (60, chemotherapy; 22, chemoradiotherapy; 15, radiotherapy),
      histopathologic effects were evaluated microscopically, and histologic response
      rates were compared among three neoadjuvant treatment modalities. Predictive
      factors for neoadjuvant therapies were analyzed by logistic regression, including
      the results of p53 immunohistochemical staining. In the chemoradiotherapy group,
      the pathologic response rate was 86.4%, and was significantly higher than that
      for chemotherapy (P < 0.0001) or for radiotherapy (P = 0.0031). In patients with
      normal p53 protein expression, the histopathologic response rate to chemotherapy
      was 20.0%, a higher rate than that for patients with abnormal p53 overexpression.
      In the chemoradiotherapy or radiotherapy group, however, the response rates were
      almost the same, irrespective of p53 oncoprotein status. From multivariate
      analysis, the neoadjuvant treatment modality itself was identified as the most
      powerful predictive factor for the effect. Chemoradiotherapy had the most
      powerful effect on advanced esophageal cancer, and p53 status did not influence
      the clinical outcome in this group.

PMID- 12060046
TI  - Differences and relationships of thymidine phosphorylase expression in tumor
      associated macrophages and cancer cells in squamous cell carcinoma of the
      esophagus.
AB  - Thymidine phosphorylase (TP), which has been shown to be identical to platelet
      derived endothelial cell growth factor, is expressed in tumor-associated
      macrophages (TAMs) as well as cancer cells. The aim of this study was to clarify
      the differences or relationships of TP expression in TAMs and cancer cells in
      esophageal squamous cell carcinoma (SCC). Tissues samples were taken from 56
      patients with esophageal SCC after curative surgery. The expression of TP in TAMs
      or SCC cells was examined using a monoclonal antibody to TP (clone 654-1).
      Microvessels in SCC that stained positively for Factor VIII-related antigen were
      counted (microvessel density, MVD). Macrophages in SCC that stained positively
      for CD68 antigen were counted (monocytic count). Ki-67 antigen was immunostained
      with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate biotin nick end labeling was performed, and Ki-67 labeling index
      (LI) and apoptotic index were calculated. The expression of TP in stromal cells
      and cancer cells was observed in 43 (76.8%) and 33 patients (58.9%),
      respectively. There were significant correlations between TP expression in
      stromal cells (TAMs) as well as in cancer cells and venous invasion, distant
      metastasis, or MVD. There was a correlation between TP expression in cancer cells
      and lymph node metastasis, and there were correlations between TP expression in
      TAMs and monocytic count or Ki-67 LI; however, there was no correlation between
      TP expression in TAMs and lymph node metastasis. On the other hand, in SCCs with
      TP expression in both TAMs and cancer cells, higher frequencies of venous
      invasion and distant metastasis, higher MVD and lower apoptotic index were
      observed than in other SCCs. The 5-year survival rate in patients with TP
      expression in both TAMs and cancer cells was poorer than that in patients with TP
      expression in neither TAMs and cancer cell. In conclusion, these results suggest
      that co-expression of TP in TAMs and cancer cells is strongly associated with
      angiogenic promotion and distant metastasis. However, other effects of TP, such
      as promotion of tumor growth and lymph node metastasis, may be different
      depending on whether these are expressed in TAMs or cancer cells in esophageal
      SCCs. Patients with coexpression of TP in TAMs and cancer cells may be associated
      with a poor prognosis.

PMID- 12060047
TI  - Changes of TGFbeta1 and TGFbetaRII expression in esophageal precancerous and
      cancerous lesions: a study of a high-risk population in Henan, northern China.
AB  - The level of transforming growth factor beta1 (TGFbeta1) and transforming growth
      factor betaII receptor (TGFbetaRII) was determined immunohistochemically in
      normal tissues and tissues with different severities of lesions (basal cell
      hyperplasia, BCH; dysplasia, DYS; carcinoma in situ, CIS; and squamous cell
      carcinoma, SCC) from surgically resected human esophagi and esophageal biopsies
      of symptom-free subjects. The samples were from an area with high esophageal
      cancer incidence in northern China (Linzhou, formerly Linxian, and nearby county
      Huixian in Henan Province). Peroxidase immunostain (ABC) and conventional
      hematoxylin and eosin stain were used. The tissue sections were incubated with
      antibodies of TGFbeta1 and TGFbetaRII overnight. The immunoreactivity was
      observed in cytoplasm of the esophageal specimen. From normal to BCH to DYS to
      CIS and to SCC, the positive immunostaining rates for TGFbeta1 increased
      significantly (P < 0.05). A linear correlation between the positive
      immunostaining rates of TGFbeta1 and the different lesions was observed (P <
      0.05). From well- to moderately- and poorly differentiated SCC, the positive
      immunostaining rates for TGFbeta1 decreased gradually, but the difference was not
      significant (P > 0.05). In contrast, with the lesions progressing from normal to
      BCH to DYS to CIS and to SCC, the positive immunostaining rates for TGFbetaRII
      decreased significantly (P < 0.05). From well- to moderately- and poorly
      differentiated SCC, the positive immunostaining rates for TGFbetaRII decreased
      significantly (P < 0.05). There was a linear correlation between the positive
      rates of TGFbetaRII and different lesions and SCC differentiation (P < 0.05). The
      present results indicated that the alterations of TGFbeta1 and TGFbetaRII is a
      frequent event in esophageal multistage carcinogenesis, the absent or lower
      expression of TGFbetaRII may lead to the loss of cell proliferation control by
      TGFbeta1 and the overexpression of TGFbeta1 may be a negative feedback response
      caused by the lower expression of TGFbetaRII protein.

PMID- 12060048
TI  - Endoscopic screening and determination of p53 and proliferating cell nuclear
      antigen in esophageal multistage carcinogenesis: a comparative study between high
      and low-risk populations in Henan, northern China.
AB  - The objective of this study was to characterize the histologic changes from
      endoscopic screening for early esophageal cancer (EC) on subjects at high
      incidence area (HIA) and low-incidence area (LIA) in Henan, China, and to further
      compare the changes in p53 and proliferating cell nuclear antigen (PCNA) in the
      multistage of human esophageal carcinogenesis from these two populations. The
      detection rate of basal cell hyperplasia (BCH) and dysplasia (DYS) was higher in
      the subjects from HIA than in those from LIA. Out of the 1568 symptom-free
      subjects examined at HIA, 10 (0.6%) cases with early squamous cell carcinoma
      (SCC) were identified. Immunoreactivity of p53 and PCNA was observed in cell
      nuclei of esophageal biopsies and surgically resected esophageal cancer specimens
      both in HIA and LIA. With the lesions progressed from normal epithelium to BCH to
      DYS to SCC, the positive-immunostaining cells expanded from basal layer to
      superficial layer, and the number of positive cells/mm2 for p53 and PCNA
      increased, and was significantly higher in HIA than in LIA among the similar
      morphological lesions (P < 0.01). The number of p53 positive cells/mm2 in SCC
      from HIA was almost fivefold higher than SCC from LIA (P < 0.01). The remarkable
      difference was also observed between HIA and LIA in DYS and BCH. The present
      results indicate that p53 protein accumulation is an important early biomarker
      for identifying high-risk subjects for EC.

PMID- 12060049
TI  - Diffuse esophageal leiomyomatosis with localized dense eosinophilic infiltration.
AB  - Diffuse esophageal leiomyomatosis is a rare cause of dysphagia. There is
      frequently a chronic inflammatory infiltrate, but here we present the first
      reported case in association with a dense infiltration of eosinophils and mast
      cells confined to the affected muscularis propria. This was successfully managed
      by long esophageal myotomy, with resolution of dysphagia and no symptomatic
      recurrence after 3 years.

PMID- 12060050
TI  - Coexistence of esophageal granular cell tumor and squamous cell carcinoma: a case
      report.
AB  - Granular cell tumors (GCTs) are relatively uncommon, usually benign and solitary
      neoplasms. Until now, about 200 cases of esophageal GCTs have been reported in
      the literature. We present a rare case of synchronous occurrence of esophageal
      GCT and moderately differentiated squamous cell carcinoma in a 40-year-old white
      woman. The GCT was detected incidentally during esophagoscopy undertaken for
      evaluation of a 4-month history of progressive solid food dysphagia. The gross
      and microscopic appearance of the GCT was typical. It was localized in the mucosa
      of the middle esophagus dystally and separately to the cancer. It revealed strong
      positive immunostaining for vimentin, S-100 protein and neuron-specific enolase,
      as well as weakly positive focal staining for Ki67 and p53 protein. Although, the
      coexistence of esophageal GCTs and cancers seems to be coincidental, the
      necessity of a careful clinical evaluation and a close follow-up of patients with
      GCT is suggested.

PMID- 12060051
TI  - Esophageal tuberculosis abscess: an unusual cause of dysphagia.
AB  - Primary esophageal tuberculosis is extremely rare. It is almost always secondary
      to tuberculosis of other organs. Abscess formation of the tuberculosis in the
      esophageal wall has not been reported in the literature previously. In this
      report, we present a case of esophageal tuberculosis abscess, with presented
      dysphagia, diagnosed by histologic evaluation of surgery specimen, without any
      other organ involvement. The unusual cause and the interesting clinical course of
      dysphagia are described.

PMID- 12060052
TI  - Symptomatic mucocele of a surgically excluded esophagus.
AB  - Isolated esophageal segments following esophageal bypass surgery may develop into
      mucus-filled dilatations (mucoceles) of the esophagus. They usually remain small
      and asymptomatic. This report describes a patient who developed a symptomatic
      esophageal mucocele 1 year after surgical exclusion of the thoracic esophagus for
      Boerhaave's syndrome.

PMID- 12060053
TI  - Insulin-treated diabetes and driving in the UK.
AB  - Diabetes, and particularly insulin-treated diabetes, has important implications
      for motor vehicle driving, largely because of its association with potential
      hypoglycaemia. For this reason, most countries operate some driving restrictions
      on insulin-treated diabetic patients, as well as systems of intermittent
      reassessment of hypoglycaemic risk. In the UK, regulations are operated by the
      Driver and Vehicle Licensing Agency (DVLA), which is an agency of the Department
      of the Environment, Transport and the Regions (DETR). They are supported by an
      Expert Panel which advises the Secretary of State on diabetes-related issues
      relating to fitness to drive. The patient organization Diabetes UK is also
      concerned with diabetes and driving issues, largely from a position of lobbying
      policy-influencers and supporting individual cases. All parties involved with
      diabetes and driving issues recognize the need for more research on the subject,
      as the current literature is flawed in design, though no convincing excess of
      accidents amongst diabetic drivers has been conclusively demonstrated. Currently
      in the UK, Class 2 vehicles (large trucks and passenger vehicles) are barred to
      diabetic drivers on insulin. European law has recently extended this to so-called
      C1 (large vans and small lorries) and D1 (minibuses) vehicles, though the law has
      recently been revised to allow individual consideration for potential diabetic C1
      drivers on insulin treatment. Diabetes and insulin-treated diabetes is an emotive
      and difficult issue, for which a stronger evidence base is urgently needed.

PMID- 12060054
TI  - Transforming growth factor-beta 1, 2, 3 and receptor type I and II in diabetic
      foot ulcers.
AB  - AIMS: To study the distribution of transforming growth factor-beta (TGF-beta) 1,
      2 and 3, and TGF-beta receptor types I and II in diabetic foot ulcers, diabetic
      skin and normal skin by immunohistochemistry, immunofluorescence and Western
      blotting. We also compared the TGF-betas with those of chronic venous ulcers.
      METHODS: Skin biopsies were obtained from the leg or the foot of non-diabetic and
      diabetic subjects, and from the edge of diabetic foot ulcers and chronic venous
      ulcers. Distribution (by immunofluorescence and immunocytochemistry) of TGF-beta
      1, 2 and 3 and TGF-beta receptors (RI and RII) was done by staining 8-microm skin
      sections using appropriate antibodies. Protein levels of TGF-beta were measured
      by Western blot analysis. RESULTS: TGF-beta3 expression was increased in the
      epithelium at the edge of diabetic foot ulcers, being more intense than diabetic
      and normal skin (P = 0.03, 0.02, respectively), as was its expression in venous
      ulcers compared with normal skin. However, TGF-beta1 expression was not increased
      in diabetic foot ulcers and chronic venous ulcers, and was comparable to diabetic
      and normal skin. There was also no increase for the receptors in diabetic foot
      ulcers. CONCLUSION: The lack of TGF-beta1 up-regulation in both diabetic foot
      ulcers and venous ulcers may explain the impaired healing in these chronic
      wounds, and could represent a general pattern for chronicity.

PMID- 12060055
TI  - Prognosis following first acute myocardial infarction in Type 2 diabetes: a
      comparative population study.
AB  - AIMS: To estimate the incidence of death and macrovascular complications after a
      first myocardial infarction for patients with Type 2 diabetes. RESEARCH DESIGN:
      In a retrospective, incidence cohort study in the Tayside Region of Scotland we
      studied all patients hospitalized with a diagnosis of first acute myocardial
      infarction from 1 April 1993 to 31 December 1994. The primary endpoint was time
      to death. Secondary endpoints were 2-year incidence of hospital admission for
      angina, myocardial infarction, stroke, heart failure, coronary angiography,
      coronary artery bypass graft (CABG) and percutaneous transluminal coronary
      angioplasty (PTCA). RESULTS: The 147 patients with Type 2 diabetes had
      significantly worse survival with an increase in relative hazard of 67% compared
      with non-diabetic patients. After adjustment for age, sex, smoking status, prior
      heart failure, prior angina, delay to hospitalization, site of infarction, drug
      therapy with aspirin, beta-blockers, streptokinase and hyperlipidaemia and
      treated hypertension, Type 2 diabetes was still associated with a 40% higher
      death rate compared with people without diabetes (P < 0.05) There was no
      significant difference in death rates in those aged over 70 years, but an
      indication of a trend in younger individuals with a four-fold increase in death
      rate in those with diabetes aged < 60 years, compared with a rate ratio of 2.6 in
      those with diabetes aged 61-70 years. CONCLUSIONS: Among hospitalized patients
      with first acute myocardial infarction, Type 2 diabetes mellitus is consistently
      associated with increased mortality and increased hospital admission for heart
      failure. The estimated 4-year survival rate is only 50%. Our results indicate
      that younger subjects with Type 2 diabetes and acute myocardial infarction are a
      high-risk group deserving of special study, and support the argument for
      aggressive targeting of coronary risk factors among patients with Type 2
      diabetes.

PMID- 12060056
TI  - Serum fatty acid composition predicts development of impaired fasting glycaemia
      and diabetes in middle-aged men.
AB  - AIMS: Dietary fatty acid intake is reflected in serum fatty acid composition.
      Studies prospectively investigating serum fatty acids and development of impaired
      fasting glycaemia (IFG) or diabetes mellitus (DM) are largely lacking. We
      assessed the association of serum fatty acid composition with development of IFG
      or DM. METHODS: Middle-aged normoglycaemic men (n = 895) participating in a
      prospective cohort study were followed up after 4 years. RESULTS: At baseline
      proportions of serum esterified and non-esterified saturated fatty acids were
      increased and polyunsaturated fatty acids decreased in men who after 4 years had
      developed IFG (n = 56) or DM (n = 34). No differences in dietary fatty acid
      composition as recorded in 4-day dietary records were noted. In logistic
      regression analyses adjusting for age; obesity; and fasting lipid, glucose and
      insulin concentrations, men with proportions of non-esterified and esterified
      linoleate in the upper third had nearly half the risk for IFG or DM compared with
      the lower third. In covariate analyses, baseline non-esterified linoleate
      proportions were associated with changes in fasting insulin and glucose
      concentrations over the 4-year follow-up. Baseline esterified fatty acid
      composition was also associated with changes in insulin. CONCLUSIONS: High serum
      linoleate proportions decreased the risk of developing IFG or DM in middle-aged
      men over a 4-year follow-up, possibly mediated in part by insulin resistance.
      These findings support recommendations to substitute vegetable fat for animal and
      dairy fat in the prevention of disturbances of glucose and lipid metabolism.

PMID- 12060057
TI  - Coefficient of failure: a methodology for examining longitudinal beta-cell
      function in Type 2 diabetes.
AB  - AIMS: We describe a new method, the determination of the coefficient of failure,
      which allows the assessment of beta-cell failure from any index of glycaemia.
      Previous methods using glycaemic thresholds and calculating time-to-failure have
      systematic deficiencies relating to bias, reproducibility and statistical power.
      Analyses using threshold methodologies and conventional survival analysis have an
      intrinsic disadvantage in that they use categorical data and thus make no
      allowance for near-failure, or progression towards failure. In contrast, the
      coefficient of failure includes all data in the analysis and takes into account
      improvement of glycaemia as well as deterioration of glycaemia. METHODS: We
      describe the use of a 'coefficient of failure' defined as the slope of the least
      squares regression line of a glycaemic index vs. time calculated for each
      individual patient on constant monotherapy. We exemplify the method using HbA1c
      levels from data from patients on chlorpropamide (n = 64) or glibenclamide (n =
      65) monotherapy in the Oxford cohort of the UKPDS. RESULTS: Chlorpropamide
      treated patients showed a mean coefficient of failure of 0.34 HbA(1c)%/year
      (0.44%/year sd) and glibenclamide-treated patients 0.50 HbA(1c)%/year (0.50%/year
      sd) (P = 0.046; unpaired two-tailed t-test). Kolmogorov-Smirnov testing
      demonstrated that the coefficients did not differ significantly from a normal
      distribution (chlorpropamide P = 0.12; glibenclamide P = 0.13). CONCLUSIONS: The
      coefficient of failure gives an estimate of beta-cell failure using any index of
      glycaemia. The coefficient is not constrained by predetermined glycaemic
      thresholds for failure and it allows the rate of decline in beta-cell function to
      be determined on any therapy or combination of therapies.

PMID- 12060058
TI  - Insulin resistance in non-diabetic subjects is associated with increased
      incidence of myocardial infarction and death.
AB  - AIMS: To compare the incidence of myocardial infarction and death in non-diabetic
      subjects with and without insulin resistance. METHODS: Population-based
      prospective cohort study, in Malmo, Sweden, of 4748 non-diabetic subjects (60%
      women), aged 46-68 years, with no history of myocardial infarction or stroke. The
      prevalence of insulin resistance was established by the homeostasis model
      assessment (HOMA) and defined as values above the sex-specific 75th percentile
      (1.80 for women and 2.12 for men). Incidence of myocardial infarction and death
      is based on record linkage with local and national registers. Cox's proportional
      hazards model was used to assess the influence of insulin resistance after
      adjustment for age, sex, hyperglycaemia, raised arterial blood pressure,
      dyslipidaemia, central obesity, smoking and leisure-time physical activity.
      RESULTS: Sixty-two subjects suffered a coronary event, and 93 subjects died
      during the 6-year follow-up period. Insulin resistance was after adjustment for
      other factors included in the insulin resistance syndrome and other potential
      confounders, associated with an increased incidence of coronary events (relative
      risk (RR) 2.18; 95% confidence interval (CI) 1.22-3.87; P = 0.008) and deaths (RR
      1.62; 1.03-2.55; P = 0.038). CONCLUSIONS: Insulin resistance, as assessed by the
      HOMA method, was in this cohort of middle-aged non-diabetic subjects associated
      with an increased incidence of myocardial infarction and death. This risk
      remained when smoking, low physical activity and factors included in the insulin
      resistance syndrome were taken into account in a stepwise regression model.

PMID- 12060059
TI  - Impaired vascular reactivity is present despite normal levels of von Willebrand
      factor in patients with uncomplicated Type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is associated with an increased risk of
      cardiovascular disease. Endothelial dysfunction is thought to be an early marker
      of atherosclerosis. The purpose of this study was to assess whether endothelial
      function, judged by measurements of flow-mediated vasodilatation (FMD) and
      nitroglycerine (NTG)-induced vasodilatation as well as serum levels of von
      Willebrand factor, was affected in patients with uncomplicated Type 2 diabetes
      and normal levels of urinary albumin excretion (UAE). SUBJECTS AND METHODS:
      Twenty-three patients with Type 2 diabetes, normal UAE and no vascular
      complications were examined. Twenty-three healthy subjects matched for age,
      gender, body mass index and resting vessel size served as controls. All
      participants were non-smokers. Endothelial function was assessed by high
      resolution ultrasound which measures changes in diameter of the brachial artery
      during flow-mediated and NTG-induced vasodilatation. We also measured serum
      levels of von Willebrand factor. RESULTS: In Type 2 diabetic patients FMD (3.2 +/
      0.5% vs. 4.8 +/- 0.5%, P = 0.019) as well as NTG-induced vasodilatation (15.9 +/
      0.6% vs. 18.5 +/- 0.9%, P = 0.021) were significantly reduced compared with
      controls. Levels of von Willebrand factor were not different between groups (0.88
      +/- 0.07 vs. 0.88 +/- 0.07 in patients and controls, respectively) and were not
      correlated to FMD or NTG-induced vasodilatation. CONCLUSION: Impaired vascular
      reactivity is present in uncomplicated Type 2 diabetes and seems to be a more
      sensitive marker of vascular dysfunction than von Willebrand factor.

PMID- 12060060
TI  - Hypertensive disorders of pregnancy in women with Type 1 and Type 2 diabetes.
AB  - AIMS: Hypertensive disorders in pregnancy are common in women with Type 1
      diabetes and can be associated with adverse fetal outcomes, but little is known
      about hypertension in pregnancy in women with Type 2 diabetes. The aim of this
      study was to compare the incidence and outcomes of, and risk factors for,
      hypertension in pregnancy in women with Type 1 and Type 2 diabetes. METHODS: One
      hundred consecutive singleton pregnancies in women with Type 2 and 100 in women
      with Type 1 diabetes were studied. Hypertension in pregnancy was classified
      according to Australasian Society for the Study of Hypertension in Pregnancy
      guidelines. Outcomes of pregnancy examined included birth weight, rates of
      caesarean section, premature delivery and special care unit admission, and
      perinatal mortality. RESULTS: The overall incidence of hypertension in pregnancy
      was similar in Type 2 and Type 1 diabetes (41% vs. 45%), but the distribution of
      subtypes differed (P = 0.028). Women with Type 2 diabetes had more chronic
      hypertension (diagnosed at < 20 weeks gestation), but less preeclampsia than
      women with Type 1 diabetes. Hypertension in pregnancy was strongly associated
      with a number of adverse outcomes, but the impact of hypertension was
      significantly less for Type 2 diabetes than it was for Type 1 (premature
      delivery, P < 0.005; admission to Special Care Unit, P < 0.01; caesarean section,
      P = 0.05). This was, in part, because the frequency of adverse outcomes was
      greater in women with preeclampsia. Nulliparity, poor glycaemic control at
      presentation, and early pregnancy blood pressure and not smoking were risk
      factors for hypertension of similar magnitude in both types of diabetes.
      Significant effects of duration of diabetes and obesity were not seen in Type 2
      subjects, but were in Type 1 (P < 0.01, P < 0.05, respectively). Early pregnancy
      albumin excretion rate was increased more frequently in Type 2 subjects than in
      Type 1 (P < 0.035), but was less strongly associated with the development of
      preeclampsia (P < 0.035). CONCLUSIONS: The incidence of hypertension in pregnancy
      is similar in Type 2 and Type 1 diabetes, but the different population
      characteristics are reflected in a significantly different pattern of types of
      hypertension. Hypertension has less impact on adverse outcomes in Type 2
      diabetes. Some risk factors for hypertension also differ between Type 2 and Type
      1 diabetes.

PMID- 12060061
TI  - No evidence for accumulation of insulin glargine (LANTUS): a multiple injection
      study in patients with Type 1 diabetes.
AB  - AIMS: Insulin glargine is a long-acting insulin analogue that is metabolically
      active for at least 24 h. We investigated the multiple-dose pharmacokinetic
      properties of insulin glargine to determine whether daily injections lead to the
      accumulation of circulating insulin levels and a corresponding decrease in blood
      glucose levels in patients with Type 1 diabetes. METHODS: Fifteen patients using
      preprandial insulin lispro (mean age 36 +/- 9 years, body mass index 24.6 +/- 2.2
      kg/m(2)) completed the study. Each patient's optimal insulin glargine dose was
      determined during a dose-finding phase. After a washout period, patients were
      treated over 12 days with a constant daily dose of insulin glargine injected in
      the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial
      insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were
      assessed hourly after the first, fourth, and eleventh injection, after which
      patients fasted for 24 h and did not use any other insulin preparation. RESULTS:
      There were no changes in daily insulin doses during the dose-finding phase
      (insulin glargine: initial dose 24 +/- 6 IU, mean change 0 +/- 3 IU; insulin
      lispro: 18 +/- 9 IU, 0 +/- 7 IU). The time course of FSI was comparable on the
      three pharmacokinetic study days. Notably, the trough FSI at the end of the
      sampling periods was almost identical (day 1, 79 +/- 56 pmol/l, day 4, 77 +/- 56
      pmol/l, day 11, 86 +/- 60 pmol/l). No changes occurred in any of the
      pharmacokinetic parameters studied. CONCLUSIONS: There is no evidence that
      insulin glargine accumulates after multiple injections over 12 days. These
      results indicate that the predetermined dose of insulin glargine will not need to
      be reduced after commencing treatment because of a risk of accumulation.

PMID- 12060062
TI  - Continuous intraperitoneal insulin infusion in patients with 'brittle' diabetes:
      favourable effects on glycaemic control and hospital stay.
AB  - AIMS: To evaluate the effects of continuous intraperitoneal insulin infusion
      (CIPII) using implantable pumps on glycaemic control and duration of hospital
      stay in poorly controlled 'brittle' Dutch diabetes patients, and to assess their
      current quality of life. METHODS: Thirty-three patients were included. Glycaemic
      control was retrospectively assessed with HbA(1c) levels acquired before
      implantation, 1 year later and at long-term follow up of 58 months. Duration of
      hospital stay the year before and the year following first implantation was
      extracted from hospital records. Determinants of long-term glycaemic response
      were sought. Self-report questionnaires were administered at 58 months follow-up
      only, to assess current psychopathology and quality of life. RESULTS: Mean
      HbA(1c) decreased from 10.0 +/- 2.3% to 9.0 +/- 1.8% (P = 0.039) 1 year after
      implantation and stabilized at 9.0 +/- 1.6% (P = 0.023) during long-term follow
      up. Median number of hospital days in the 20 patients suffering from hospital
      admission before implantation decreased from 45 the year before implantation to
      13 the year after (P = 0.005). Patients with a higher baseline HbA(1c) showed a
      larger long-term response (P < 0.001). Relatively low levels for quality of life
      were found, as well as a higher than expected number of patients with psychiatric
      symptoms. CONCLUSIONS: CIPII proved effective in complex patients with a history
      of poor control and hospital admission. Despite a substantial long-term
      improvement in glycaemic control and diminished hospital stay, normal levels of
      glycaemic control and quality of life were not attained.

PMID- 12060063
TI  - Glucose intolerance and associated factors in Mongolia: results of a national
      survey.
AB  - AIMS: Prevalence of glucose intolerance-diabetes and impaired glucose tolerance
      (IGT)-and of related conditions such as obesity and hypertension, was studied in
      six population samples in Mongolia in 1999. METHODS: Diagnosis of glucose
      intolerance was made on the basis of 2-h blood glucose concentration, according
      to criteria recommended by the latest report of a WHO Expert Group. RESULTS:
      Crude prevalence of diabetes was 2.9% (2.6% in men and 3.2% in women). Prevalence
      of IGT was 10.2% (9.3% in men and 10.8% in women). Age standardization to the
      standard world population of Segi resulted in a total sample prevalence of 3.1%
      for diabetes and 9.2% for IGT. Prevalence of abnormal glucose tolerance differed
      according to district of residence. Approximately one-third of the subjects with
      diabetes were diagnosed prior to the survey. Of those who were diagnosed
      previously, approximately one-half were not under any form of treatment. Subjects
      with abnormal glucose tolerance were older, more obese and had higher blood
      pressure and prevalence of hypertension than those with normoglycaemia. One-half
      of men and almost one-half of women were hypertensive. Three-quarters of the
      diabetic subjects were hypertensive. One-third of all subjects were centrally
      obese. Considering the conditions of principal interest-glucose intolerance,
      hypertension and obesity-one-half of all subjects demonstrated one or more of
      these conditions. Central obesity was the most common condition, followed by
      hypertension and then glucose intolerance. Central obesity and hypertension was
      the most common combination (17% of all subjects) and 4% exhibited all three
      conditions. CONCLUSIONS: Non-communicable diseases are already a threat to public
      health in Mongolia. Although the prevalence of diabetes is not high by
      international standards, the relatively high prevalence of IGT suggests that the
      situation may deteriorate in the future in the absence of concerted action to
      prevent and control diabetes and related conditions.

PMID- 12060064
TI  - Diabetes care in Kilimanjaro region: clinical presentation and problems of
      patients of the diabetes clinic at the regional referral hospital-an inventory
      before structured intervention.
AB  - BACKGROUND: In order to improve care for diabetic patients in a developing
      country at the regional referral hospital for the Northern zone of Tanzania, a
      specialized clinic was established in November 1996. AIM: The aim of this study
      was to provide a situational analysis about the problems of the diabetic patient
      population treated at the hospital. For all patients who registered at the clinic
      a questionnaire was completed about personal data, diabetes history, symptoms,
      treatment, eating habits and psycho-social aspects of the disease. Results from
      patients who registered between November 1996 and December 1998 were analysed.
      RESULTS: Data from 474 diabetic patients (46% female) were obtained. Mean age was
      53.75 (+/- 16; range 4-88 years), 15% were classified Type 1, 75% Type 2 and 10%
      remained unclassified. A body mass index of < 25 was recorded in > 80% of the
      Type 1 and approx. 50% of the Type 2 patients. Among complications, numbness of
      the legs was mentioned by 44%, hypertension was diagnosed in about 25%,
      retinopathy in 14%, foot ulcers in 10% and nephropathy in 7.5% of the patients.
      About 50% of the patients saw their disease as a big physical and psychological
      problem. Monthly cost for an average insulin-treated patient equalled around 25%
      of the minimal wage. CONCLUSION: Diabetes care in a developing country needs to
      address the specific background of the patient population, their needs, the
      medical problems and the social constraints. Active participation of the patients
      can help to overcome some of the difficulties.

PMID- 12060065
TI  - Reproducibility of individualized coronary heart disease risk calculations in
      patients with diabetes mellitus.
AB  - AIMS: To determine prospectively, the reproducibility of individualized coronary
      heart disease (CHD) risk estimations in a high-risk (diabetic) population.
      METHODS: One hundred and three patients attending a hospital diabetes clinic who
      were in the primary prevention category for CHD had measurements of cholesterol,
      HDL-cholesterol and systolic blood pressure (SBP) performed in one of 13 general
      practices and then 2 weeks later in the hospital clinic. The data were combined
      with age, sex, smoking history and diabetic status data to produce a 10-year CHD
      risk estimate for each occasion using the Framingham algorithm. RESULTS: The
      coefficients of variation for cholesterol, HDL and SBP were 6.0%, 9.4% and 7.0%,
      respectively. When classified by treatment thresholds of 15% and 30% 10-year CHD
      risk, 88% of patients were classified in the same category on both occasions.
      Kappa values for the 15% and 30% risk thresholds were 0.71 and 0.82. This
      indicates good interobserver agreement for the estimation of CHD risk. The use of
      a single BP rather than the mean of two, resulted in seven of 206 estimations of
      CHD risk performed in 103 patients crossing a risk threshold, with 6/7 being
      placed in a higher risk category. CONCLUSIONS: Estimation of CHD risk on a single
      occasion is sufficient to make robust treatment decisions based on risk
      thresholds. Use of a single BP measurement rather than the mean of two
      overestimates the risk category in around 3% of cases.

PMID- 12060066
TI  - Predictivity of thyroid autoantibodies for the development of thyroid disorders
      in children and adolescents with Type 1 diabetes.
AB  - AIMS: To investigate the prevalence of thyroid autoantibodies and their
      significance for the development of thyroid disorders in children and adolescents
      with Type 1 diabetes. METHODS: Antibodies to thyroglobulin (anti-TG) and
      thyroperoxidase (anti-TPO) were measured in 216 patients (113 boys; median age
      12.9 years (range 1-22 years)) with Type 1 diabetes (diabetes duration 2.5 years
      (0-14 years)) in a cross-sectional study. Sixteen patients with significantly
      elevated anti-TPO titres were followed longitudinally (6.0 years (4-13 years))
      including the measurement of anti-TPO, anti-TG, T(3), T(4), thyroid-stimulating
      hormone (TSH) and ultrasound assessment. RESULTS: Twenty-two patients (10.0%) had
      significantly elevated titres of anti-TPO, 19 (8.7%) of anti-TG and 13 (5.9%) of
      both autoantibodies. Girls had more frequently elevated anti-TPO antibodies than
      boys (P < 0.05). Eight of 16 patients (50%) developed thyroid disorders defined
      by a TSH elevation (> or = 4.5 microU/ml) and/or sonographic thyroid
      abnormalities during a median time of 3.5 years (2-6 years) after first detection
      of anti-TPO positivity. They were characterized by higher levels of anti-TPO (P =
      0.001) and a more frequent coexistence of anti-TG antibodies (P = 0.002) than
      those with no development of thyroid disorder even after an observation period of
      5.5 years (5-10 years). CONCLUSIONS: Because 50% of children with diabetes and
      significant titres of anti-TPO develop thyroid problems within 3-4 years,
      examinations of thyroid antibodies should be performed yearly. In cases of
      significant antibody titres, thyroid function tests and ultrasound assessment are
      recommended in order to minimize the risk of undiagnosed hypothyroidism in these
      patients.

PMID- 12060068
TI  - Developmental expression patterns of alpha1H T-type Ca2+ channels during
      spermatogenesis and organogenesis in mice.
AB  - The objectives of the present study were to investigate the expression patterns
      of T-type Ca2+ channel mRNA during spermatogenesis and organogenesis in mice.
      Reverse transcription-polymerase chain reaction (RT-PCR) was performed to
      identify the subtypes of calcium channels present in the round spermatids
      isolated from mouse testes by flow cytometry. Transcripts of L-type (alpha1D),
      non-L-type (alpha1E) and T-type Ca2+ channels were detected in round spermatids.
      Analysis of PCR products of T-type Ca2+ channels indicated that only alpha1H
      subunits were detected in round spermatids. The appearance and differential
      distribution of alpha1H T-type Ca2+ channel mRNA during mouse spermatogenesis and
      postimplantation embryogenesis (embryonic (E) days E9, E12, E15) were
      investigated by in situ hybridization with digoxigenin-labeled RNA probes coupled
      with alkaline phosphatase detection. In testes from adult and immature mice
      (postnatal 2 and 3 weeks), alpha1H T-type Ca2+ channel mRNA was expressed in all
      developing germ cells and sertoli cells. On E9 and E12, tissues of the central
      nervous system, such as the telencephalon, expressed alpha1H T-type Ca2+ channel
      mRNA. On E15, signals were detected throughout all organs of the embryo. These
      findings indicate that the expression of alpha1H T-type Ca2+ channels is spatio
      temporally regulated during spermatogenesis and organogenesis.

PMID- 12060069
TI  - Planarian fibroblast growth factor receptor homologs expressed in stem cells and
      cephalic ganglions.
AB  - The strong regenerative capacity of planarians is considered to reside in the
      totipotent somatic stem cell called the 'neoblast'. However, the signal systems
      regulating the differentiation/growth/migration of stem cells remain unclear. The
      fibroblast growth factor (FGF)/FGF receptor (FGFR) system is thought to mediate
      various developmental events in both vertebrates and invertebrates. We examined
      the molecular structures and expression of DjFGFR1 and DjFGFR2, two planarian
      genes closely related to other animal FGFR genes. DjFGFR1 and DjFGFR2 proteins
      contain three and two immunoglobulin-like domains, respectively, in the
      extracellular region and a split tyrosine kinase domain in the intracellular
      region. Expression of DjFGFR1 and DjFGFR2 was observed in the cephalic ganglion
      and mesenchymal space in intact planarians. In regenerating planarians,
      accumulation of DjFGFR1-expressing cells was observed in the blastema and in
      fragments regenerating either a pharynx or a brain. In X-ray-irradiated
      planarians, which had lost regenerative capacity, the number of DjFGFR1
      expressing cells in the mesenchymal space decreased markedly. These results
      suggest that the DjFGFR1 protein may be involved in the signal systems
      controlling such aspects of planarian regeneration as
      differentiation/growth/migration of stem cells.

PMID- 12060070
TI  - Identification and characterization of a unique Xenopus laevis egg envelope
      component, ZPD.
AB  - We report the identification of a previously undetected Xenopus laevis egg
      envelope component discovered through cloning experiments. A cDNA sequence was
      found that represented a mature protein of 32 kDa. Peptide antibodies were
      generated to probe for the protein in egg envelope samples and reactivity was
      found to a glycoprotein of approximately 80 kDa. When deglycosylated egg envelope
      samples were probed, a 32 kDa protein was labeled, confirming the size of the
      translated cDNA sequence. A BLAST analysis showed that it is most closely related
      (34% amino acid identity) to the ZP domains of mammalian tectorin, uromodulin and
      ZPA. From a dendrogram of known egg envelope glycoproteins, the new glycoprotein
      was shown to be unique among egg envelope components and was designated ZPD. A
      similar glycoprotein was identified by immunocrossreactivity in Xenopus
      tropicalis and Xenopus borealis egg envelopes.

PMID- 12060071
TI  - A novel Dictyostelium Cdk8 is required for aggregation, but is dispensable for
      growth.
AB  - When Dictyostelium cells starve, they express genes necessary for aggregation.
      Using insertional mutagenesis, we have isolated a mutant that does not aggregate
      upon starvation and that forms small plaques on bacterial lawns, thus indicating
      slow growth. Sequencing of the mutated locus showed a strong similarity to the
      catalytic domain of cdc2-related kinase genes. Phylogenetic analysis further
      indicated that the amino acid sequence was more close to cyclin-dependent kinase
      8 than to the sequence of other cyclin-dependent kinases. Thus, we designated
      this gene as Ddcdk8. The Ddcdk8-null cells do not aggregate and grow somewhat
      more slowly than parental cells when being shaken in axenic medium or laid on
      bacterial plates. To confirm whether these defective phenotypes were caused by
      disruption of this gene, the Ddcdk8-null cells were complemented with DdCdk8
      protein expressed from an endogenous promoter, but not an actin promoter, and
      when the complemented cells were then allowed to grow on a bacterial lawn, they
      began to aggregate as the food supply was depleted and finally became fruiting
      bodies. The results suggest that properly regulated DdCdk8 activity is essential
      for aggregation. Because, when starved, Ddcdk8-null cells do not express the acaA
      transcripts required for aggregation, we deduce that Ddcdk8 is epistatic for acaA
      expression, indicating that the DdCdk8 products may regulate expression of acaA
      and/or other genes.

PMID- 12060072
TI  - Lineage of anuran epidermal basal cells and their differentiation potential in
      relation to metamorphic skin remodeling.
AB  - The anuran remodels the larval epidermis into the adult one during metamorphosis.
      Larval and adult epidermal cells of the bullfrog were characterized by
      determining the presence of huge cytoplasmic keratin bundles and the expression
      profiles of specific marker genes, namely colalpha1 (collagen alpha1 (I)), rlk
      (larval keratin) and rak (adult keratin). We identified four types of epidermal
      basal cells: (i) basal skein cells that have keratin bundles and express
      colalpha1 and rlk; (ii) rak+-basal skein cells that have keratin bundles and
      express colalpha1, rlk, and rak; (iii) larval basal cells that express rlk and
      rak; and (iv) adult basal cells that express rak. These traits suggested that
      these basal cells are on the same lineage in which basal skein cells are the
      original progenitor cells that consecutively differentiate into rak+-basal skein
      cells into larval basal cells, and finally into adult basal cells. To directly
      verify the differentiation potential of larval basal cells into adult ones, the
      mono-layered epidermis composed of larval basal cells was cultured in the
      presence of aldosterone and thyroid hormone. In this culture, larval basal cells
      differentiated into adult basal cells that reconstituted the adult epidermis.
      Thus, it was concluded that larval basal cells are the direct progenitor cells of
      the adult epidermal stem cells.

PMID- 12060073
TI  - Specification and differentiation processes of secondary mesenchyme-derived cells
      in embryos of the sea urchin Hemicentrotus pulcherrimus.
AB  - Four types of mesoderm cells (pigment cells, blastocoelar cells, coelomic pouch
      cells and circumesophageal muscle cells) are derived from secondary mesenchyme
      cells (SMC) in sea urchin embryos. To gain information on the specification and
      differentiation processes of SMC-derived cells, we studied the exact number and
      division cycles of each type of cell in Hemicentrotus pulcherrimus. Numbers of
      blastocoelar cells, coelomic pouch cells and circumesophageal muscle fibers were
      18.0 +/- 2.0 (36 h post-fertilization (h.p.f.)), 23.0 +/- 2.5 (36 h.p.f.) and 9.5
      +/- 1.3 (60 h.p.f.), respectively, whereas the number of pigment cells ranged
      from 40 to 60. From the diameters of blastocoelar cells and coelomic pouch cells,
      the numbers of division cycles were elucidated; these two types of cells had
      undertaken 11 rounds of cell division by the prism stage, somewhat earlier than
      pigment cells. To determine the relationship among the four types of cells, we
      tried to alter the number of pigment cells with chemical treatment and found that
      CH3COONa increased pigment cells without affecting embryo morphology.
      Interestingly, the number of blastocoelar cells became smaller in CH3COONa
      treated embryos. In contrast, blastocoelar cells were markedly increased with
      NiCl2 treatment, whereas the number of pigment cells was markedly decreased. The
      number of coelomic pouch cells and circumesophageal muscle fibers was not
      affected with these treatments, indicating that coelomic pouch and muscle cells
      are specified independently of, or at much later stages, than pigment and
      blastocoelar cells.

PMID- 12060074
TI  - Expression of crystallin genes in embryonic and regenerating newt lenses.
AB  - The spatio-temporal expression of three crystallin genes (alphaA, betaB1 and
      gamma) in the developing and regenerating lenses of newt was compared by in situ
      hybridization in lens differentiation in normal development with during
      regeneration. In normal development, all crystallin transcripts were first
      detected at the same stage in the posterior region of the lens vesicle
      (McDevitt's lens development stage V) and continued during lens fiber
      differentiation of the posterior cells into the primary lens fiber cell
      differentiation (McDevitt's lens development stage VII-VIII). At later stages,
      the expression of the three genes was restricted to the secondary lens fibers and
      gradually became undetectable in primary lens fibers (McDevitt's lens development
      stage X). The signal for gamma-crystallin was never detected in lens epithelium
      at any stage, whereas signals for alphaA- and betaB1-crystallin were detected in
      the lens epithelium at the stage when the primary lens fiber mass was formed.
      During lens regeneration, signals for the three crystallins were first detected
      at the same stage at the ventral margin of a regenerating lens vesicle (Sato's
      lens regeneration stage IV). The expression patterns of three crystallin genes
      were similar to those in normal development (Sato's lens regeneration stage V-X).
      The expression pattern of the crystallin genes in normal lens development
      fundamentally resembles that during lens regeneration, suggesting the absence of
      unique expression programs of crystallin genes for lens regeneration not found in
      ontogeny.

PMID- 12060075
TI  - Cervical cancer audit: and what is quality?

PMID- 12060076
TI  - Peripheral endothelial cells are not reliable in differentiating primary benign
      and malignant hepatocellular lesions in fine needle aspirates of the liver.
AB  - The distinction of hepatocellular carcinoma (HCC) from benign lesions of the
      liver in fine needle aspiration (FNA) specimens can be problematic. In an attempt
      to separate well-differentiated HCC from benign hepatocellular lesions, the
      presence of tissue fragments displaying peripheral endothelial cells (PE) has
      been proposed in a previous study as a useful feature in favour of malignancy. In
      this study, we evaluated slides from 59 cases of liver masses undergoing FNA (19
      HCC, 40 benign) and evaluated them for the presence of tissue fragments
      containing PE. We found that 90% of cases of HCC contained tissue fragments in
      which PE were either focally present or abundant. However, 68% of cases
      containing only benign hepatocytes also contained tissue fragments in which PE
      were at least focally present. In addition, it appears that within the group of
      benign lesions, the presence of PE was related to the overall cellularity of the
      specimen rather than the specific nature of the lesion. Thus, the presence of PE
      in tissue fragments does not, in isolation, appear to be a useful morphological
      feature for the separation of benign and malignant hepatocellular lesions in FNA
      material.

PMID- 12060077
TI  - Evaluation of liquid-based cytology in cervical screening of high-risk
      populations: a split study of colposcopy and genito-urinary medicine populations.
AB  - A split study evaluated the ThinPrep(R) PapTesttrade mark (TP; Cytyc Corp.,
      Boxborough, MA) compared with current methodologies of cervical cytology in two
      high-risk cohorts. One thousand, three hundred cases from a colposcopy clinic and
      a genito-urinary medicine outpatient clinic were examined. The TP reported
      increased detection of all grades of dyskaryosis (mild, moderate and severe; +
      4.5%) and a decrease in borderline and unsuitable cases (- 4.9%). Four cases of
      high-grade dyskaryosis (moderate or severe) were detected only using the TP,
      while an additional four cases classified as high-grade dyskaryosis with the TP
      were reported as borderline by our conventional methods. The split-study finding
      of increased sensitivity with the TP provides for improved clinical management of
      patients in our high-risk cohorts.

PMID- 12060078
TI  - Cytological findings of invasive micropapillary carcinoma of the breast: a report
      of two cases.

PMID- 12060079
TI  - Fine needle aspiration cytology of metastatic malignant granular cell tumour: a
      case report and review of the literature.

PMID- 12060080
TI  - Pale cells in a cervical smear.

PMID- 12060081
TI  - Cystic hypersecretory hyperplasia of the breast: diagnosis on fine needle
      aspiration cytology.

PMID- 12060082
TI  - Fine needle aspiration cytology of adenoid cystic carcinoma of the breast.

PMID- 12060083
TI  - Cytological features of fibrolamellar variant of hepatocellular carcinoma with
      review of literature.

PMID- 12060084
TI  - Cytological diagnosis of multiple myeloma in a 13-year-old boy.

PMID- 12060085
TI  - Squash cytology of cerebellar haemangioblastoma.

PMID- 12060086
TI  - Metastatic astrocytoma in the parotid.

PMID- 12060087
TI  - Fine needle aspiration cytology of non-Hodgkin's lymphoma of thyroid.

PMID- 12060093
TI  - Statistical techniques for comparing measurers and methods of measurement: a
      critical review.
AB  - 1. Clinical and experimental pharmacologists and physiologists often wish to
      compare two methods of measurement, or two measurers. 2. Biostatisticians insist
      that what should be sought is not agreement between methods or measurers, but
      disagreement or bias. 3. If measurements have been made on a continuous scale,
      the main choice is between the Altman-Bland method of differences and least
      products regression analysis. It is argued that although the former is relatively
      simple to execute, it does not distinguish adequately between fixed and
      proportional bias. Least products regression analysis, although more difficult to
      execute, does achieve this goal. There is almost universal agreement among
      biostatisticians that the Pearson product-moment correlation coefficient (r) is
      valueless as a test for bias. 4. If measurements have been made on a categorical
      scale, unordered or ordered, the most popular method of analysis is to use the
      kappa statistic. If the categories are unordered, the unweighted kappa statistic
      (K) is appropriate. If the categories are ordered, as they are in most rating
      scales in clinical, psychological and epidemiological research, the weighted
      kappa statistic (K(w)) is preferable. But K(w) corresponds to the intraclass
      correlation coefficient, which, like r for continuous variables, is incapable of
      detecting bias. Simple techniques for detecting bias in the case of ordered
      categorical variables are described and commended to investigators.

PMID- 12060094
TI  - Altered mitogen-activated protein kinase activation in vascular smooth muscle
      cells from spontaneously hypertensive rats.
AB  - 1. We previously reported that activation function of mitogen-activated protein
      kinases (MAPK) is enhanced in aorta strips from both prehypertensive and
      hypertensive spontaneously hypertensive rats (SHR) and that this enhancement of
      MAPK activation results from enhanced MAPK activation reactivity to angiotensin
      (Ang) II in SHR aorta strips. 2. The purpose of the present study was to examine
      whether the enhanced function of the vascular angiotensin system observed in SHR
      aorta strips results from genetic alterations of vascular smooth muscle cells
      from SHR. 3. Basal MAPK activity was within normal limits in cells from 4-week
      old SHR, whereas enzyme activity was enhanced in 9-week-old SHR compared with age
      matched Wistar-Kyoto (WKY) rats. 4. Mitogen-activated protein kinase activation
      reactivity to AngII and endothelin-1 was enhanced in 9-week-old SHR cells but not
      in 4-week-old SHR cells. The enhancement of basal MAPK activity in 9-week-old SHR
      cells was abolished by a combination of the angiotensin AT(1) receptor antagonist
      losartan and the endothelin receptor antagonist BQ123. 5. These findings suggest
      that MAPK activation function in 4-week-old SHR cells is not enhanced. Thus, it
      appears that factors outside vascular smooth muscle cells are needed for the
      enhanced MAPK activation observed in 4-week-old SHR aorta strips. In 9-week-old
      SHR, MAPK activation function is enhanced in cells themselves and this function
      may, at least in part, contribute to the enhanced MAPK activation observed in SHR
      aorta strips.

PMID- 12060095
TI  - Insulin-enhanced liposome-mediated gene transfer into a gastric carcinoma cell
      line.
AB  - 1. Liposome-mediated transfection is useful due to no DNA constraints, lower
      immunogenicity and easy preparation. However, it has the disadvantage of low
      transfection efficiency. We aimed to test whether lipofection efficiency could be
      enhanced in gastrointestinal cell lines by the growth-promoting effect of
      insulin. 2. To assess the effect of insulin on lipofection efficiency and the
      cell cycle, expression of green fluorescent protein (GFP) and DNA distribution in
      gastric (MKN1), colonic (HT29) and pancreatic (BxPC3) carcinoma cell lines was
      analysed using flow cytometry. 3. The percentage of positive cells with GFP was
      significantly higher in MKN1 cells in culture medium with 5 mg/mL insulin than
      without insulin, whereas the percentage was the same in HT29 and BxPC3 cells with
      insulin as without insulin. The percentage of S phase fraction MKN1 cells with
      insulin was greater than without insulin, whereas the percentage of S phase
      fractions of HT29 and BxPC3 cells was the same with or without insulin.
      Lipofection efficiency correlated with the percentage of S phase fraction. 4.
      Insulin has the potential to enhance efficiency of lipofection into a sensitive
      cell line by increasing cellular proliferation.

PMID- 12060096
TI  - Effects of melanocortins on cardiovascular regulation in rats.
AB  - 1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH)
      has been attributed a cardiovascular effect, inducing an increase in blood
      pressure and heart rate. Although still controversial, this effect, based on
      pharmacological blockade experiments, is supposed to be mediated through
      sympathetic activation. 2. The aims of the present study were to identify the N
      terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence
      blood pressure and heart rate and to investigate the real-time changes in
      baroreflex sensitivity and in sympathetic and vagal modulation underlying
      cardiovascular effects in conscious rats without the use of pharmacological
      blockade. 3. Intracerebroventricular administration of different melanocortins
      and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol
      onwards, with only a small initial bradycardic response with the highest dose. 4.
      Coinciding with this pressor response, an elicitation of the low-frequency (LF)
      component was observed in spectral analysis of both blood pressure variability
      (BPV) and heart rate variability (HRV), followed by the high-frequency (HF)
      component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After
      intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent
      pressor and cardioaccelerator response with very rapid onset with concentrations
      from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex
      sensitivity and simultaneously increased both components of BPV, with a radical
      reduction of the LF component and a preserved vagal HF component in HRV. 7. Of
      all the intravenously administered melanocortins, only gamma(2)-MSH was active.
      The central effect is likely to depend on an increase of (alpha-)sympathetic
      outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a
      baroreceptor reflex-blocking agent, being compatible with a role in the acute
      stress response.

PMID- 12060097
TI  - Caffeine decreases the expression of Na+/K+-ATPase and the type 3 Na+/H+
      exchanger in rat kidney.
AB  - 1. The aim of the present study was to explore the mechanisms underlying the
      renal effects of caffeine. 2. Male Sprague-Dawley rats were treated with
      caffeine, consisting of a single oral bolus (0.2%, 20 mL/kg) followed by
      supplementation in drinking water (0.2%) for 1 day. Rats treated the same but
      given water without caffeine served as controls. 3. The expression of alpha1- and
      beta1-subunits of Na+/K+-ATPase, the type 3 Na+/H+ exchanger (NHE3) and aquaporin
      1 was determined in the kidney by western blot analysis. 4. To explore possible
      involvement of local humoral mediators, the tissue expression of nitric oxide
      synthase (NOS) proteins was determined by western blot analysis and the
      expression of atrial natriuretic peptide (ANP) mRNA was determined by
      semiquantitative reverse transcription-polymerase chain reaction. 5. Following
      treatment with caffeine, the expression of alpha1- and beta1-subunits of Na+/K+
      ATPase, as well as that of NHE3, was decreased. Accordingly, the catalytic
      activity of Na+/K+-ATPase was decreased. In contrast, the expression of aquaporin
      1 was not altered significantly. 6. The expression of the endothelial isoform of
      NOS was increased, along with tissue nitrite/nitrate levels. The expression of
      ANP mRNA was increased. 7. It is suggested that caffeine decreases Na+/K+-ATPase
      and NHE3 activities and increases nitric oxide and ANP activities in the kidney.

PMID- 12060099
TI  - Involvement of alpha-calcitonin gene-related peptide in heat stress-induced
      delayed preconditioning in rat hearts.
AB  - 1. Previous studies have shown that hyperthermia is capable of activating
      capsaicin-sensitive sensory nerves and stimulating the release of
      neurotransmitters from their peripheral terminals. Calcitonin gene-related
      peptide (CGRP) has recently been found to participate in delayed cardioprotection
      in rat isolated hearts. 2. The purpose of the present study was to explore
      whether the delayed cardioprotection by heat stress in vivo involves the
      expression and release of CGRP. 3. Sprague-Dawley rats were pretreated with whole
      body hyperthermia (rectal 42 degrees C) for 15 min, 24 h before the experiments
      and then the left main coronary artery of rat hearts was subjected to a 45 min
      occlusion followed by 3 h reperfusion. The degree of myocardial injury was
      evaluated by measurement of infarct size and plasma creatine kinase (CK)
      activity. The plasma levels of CGRP and expression of CGRP (alpha and beta
      isoforms) mRNA in lumbar dorsal root ganglia at 4, 8, 16 or 24 h after heat
      stress treatment were measured. 4. Pretreatment with hyperthermia significantly
      reduced infarct size and CK release. Heat stress also significantly increased
      plasma concentrations of CGRP and the expression of alpha-CGRP mRNA, but not beta
      CGRP mRNA. The effect of heat stress was completely abolished by pretreatment
      with capsaicin (50 mg/kg, s.c.), which selectively depletes transmitters in
      capsaicin-sensitive sensory nerves. 5. In summary, the results suggest that the
      delayed cardioprotection by heat stress involves the synthesis and release of
      CGRP and that the protection is mainly mediated by the alpha-CGRP isoform.

PMID- 12060098
TI  - Involvement of oxidative stress in bee venom-induced inhibition of Na+/glucose
      cotransporter in renal proximal tubule cells.
AB  - 1. The present study was conducted to examine the involvement of oxidative stress
      in bee venom-induced inhibition of the Na+/glucose cotransporter (alpha-methyl-d
      glucopyranoside (alpha-MG) uptake), a typical functional marker of proximal
      tubules, in primary cultured rabbit renal proximal tubule cells (PTC). 2. Bee
      venom (> or = 1 microg/mL) increased lipid peroxide (LPO) formation over 30 min.
      The increase in [(3)H]-arachidonic acid (AA) release and LPO formation and the
      inhibition of alpha-MG uptake induced by bee venom (1 microg/mL) and melittin (a
      major component of bee venom; 0.5 microg/mL) were blocked by N-acetyl-l-cysteine,
      vitamin C and vitamin E, anti-oxidants. 3. Bee venom- and melittin-induced
      increases in LPO formation and inhibition of alpha-MG uptake were significantly
      prevented by mepacrine and AACOCF(3), phospholipase A(2) inhibitors. In addition,
      nordihydroguaiareic acid (a lipoxygenase inhibitor) and econazole (a cytochrome P
      450 epoxygenase inhibitor), but not indomethacin (a cyclo-oxygenase inhibitor),
      prevented bee venom- and melittin-induced increases in LPO formation and
      inhibition of alpha-MG uptake. 4. Nordihydroguaiareic acid prevented bee venom-
      and melittin-induced increases in Ca(2+) uptake. Moreover, anti- oxidants
      significantly prevented bee venom- and melittin-induced increases in Ca(2+)
      uptake. 5. In conclusion, bee venom inhibits alpha-MG uptake via the
      phospholipase A(2)-oxidative stress-Ca(2+) signalling cascade in primary cultured
      rabbit renal proximal tubule cells.

PMID- 12060100
TI  - Role of CA(2+)-activated K+ channels in the regulation of basilar arterial tone
      in spontaneously hypertensive rats.
AB  - 1. Ionic channels appear to play an important role in contractile responses of
      the cerebral arteries and, thereby, contribute to the regulation of cerebral
      circulation. In the present study, we investigated the role of large-conductance
      Ca(2+)-activated K+ (BK(Ca)) channels in the regulation of cerebral arterial tone
      during chronic hypertension. 2. Ring segments of the basilar artery from
      spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats
      were placed in bath chambers and the isometric tension of each ring was measured.
      3. Application of inhibitors of BK(Ca) channels, namely tetraethylammonium (TEA;
      > or = 0.1 mmol/L) and charybdotoxin (CTX; > or = 0.1 nmol/L), produced
      spontaneous contraction with rhythmic oscillation in the basilar artery from SHR.
      4. The oscillatory contraction was not induced by 5-hydroxytryptamine (0.01-10
      micromol/L) or depolarization by external high K+ (20-60 mmol/L). 5. The rhythmic
      contraction was completely abolished by either the removal of external Ca(2+) or
      the application of nicardipine (10 nmol/L). 6. The oscillation was not affected
      by the substitution of external Cl(-) by various equimolar anions (i.e. acetate,
      benezenesulphonate, bromide and isethianate). 7. The amplitude of the oscillation
      was dose-dependently increased by the vasodilators forskolin and sodium
      nitroprusside, as well as by stimulation of the endothelium with histamine and
      acetylcholine, whereas the frequency was decreased. 8. In contrast, the
      oscillation was eliminated by depletion of Ca(2+) stores by caffeine. Neither TEA
      (10 mmol/L) nor CTX (10 nmol/L) produced any significant contraction of the
      basilar artery in WKY rats. 9. These results suggest that BK(Ca) channels may
      play an important role in regulating the resting tone of the cerebral artery in
      SHR.

PMID- 12060101
TI  - Effects of a 1 day fast on biohumoral variables associated with human circadian
      rhythmicity.
AB  - 1. The aim of the present study was to investigate the effects of a short (1 day)
      fast by testing biohumoral variables associated with the human circadian rhythm.
      2. Fifteen clinically healthy male volunteers (32 +/- 8 years old) participated
      in the study. Subjects were fed a control diet for 7 days. The last day was a
      control day and the following 8th day was the fasting day. Each subject was asked
      to collect urine seven times over a 24 h period. Chemical and hormonal variables
      were measured in each fractionated urine specimen. The time- qualified urinary
      excretion rates were biometrically analysed using conventional and
      chronobiological methods. 3. During fasting, significant incremental changes were
      detected in the urinary excretion rates of potassium, aldosterone, 17
      hydroxycorticosteroids and adrenaline and significant decremental changes were
      detected in the excretion rates of sodium, chloride, creatinine, urea nitrogen,
      uric acid, 17-ketosteroids, noradrenaline and dopamine. The circadian rhythmicity
      of the variables was well preserved and remained almost stable throughout the
      fasting phase. 4. Fasting affected the mean oscillatory levels and oscillatory
      amplitudes of variables, suggesting that nutrients may have played roles as tonic
      and phasic modulators on the mechanisms that physiologically regulate ircadian
      rhythmicity.

PMID- 12060102
TI  - Selective peripheral regulation of noradrenaline and adrenaline release by nitric
      oxide.
AB  - 1. Nitric oxide (NO) has complex effects on the sympathoadrenal and
      cardiovascular systems and may act at both central and peripheral loci. Nitric
      oxide appears to act directly on blood vessels and indirectly by modulating the
      sympathoadrenal system. In the present study, we investigated the contribution of
      catecholamine release from peripheral vascular and adrenal sympathetic nerves to
      the cardiovascular effects of the NO synthesis inhibitor N(G)-nitro-L-arginine
      methyl ester (L-NAME; 10 mg/kg). Our experiments were performed in pithed
      vagotomized rats to remove the influence of central and baroreflex pathways. 2.
      Spinal cord stimulations for 30 s periods at 1, 2, 5 and 10 Hz using pulses of 1
      msec at 10 V caused marked increases in plasma adrenaline and noradrenaline. N(G)
      Nitro-L-arginine methyl ester did not alter resting plasma catecholamine
      concentrations. However, L-NAME generally more than doubled stimulation-evoked
      release of adrenaline while reducing the extent of noradrenaline release relative
      to vehicle (saline)-treated controls. 3. N(G)-Nitro-L-arginine methyl ester
      significantly enhanced the vasopressor responses to spinal cord stimulation. The
      alpha1-adrenoceptor antagonist prazosin (0.2 mg/kg) reduced the pressor responses
      of electrically stimulated L-NAME-treated rats to levels below those of vehicle
      treated control rats. 4. In the absence of electrical stimulation, L-NAME raised
      the blood pressure of pithed rats without altering plasma catecholamines and the
      pressor effect was briefly attenuated by L-arginine, but was unaffected by
      prazosin. 5. We conclude that the augmented pressor response to sympathetic
      stimulation in L-NAME-treated pithed rats is due largely to enhanced adrenal
      adrenaline release mediated by a peripheral mechanism. Stimulation of alpha(1)
      adrenoceptors plays a major role in the pressor response to electrical
      stimulation of L-NAME-treated rats, but this is not due to L-NAME augmentation of
      noradrenaline release from vascular sympathetic nerves.

PMID- 12060104
TI  - Effects of blockade of alpha- and beta-adrenoceptors and neuropeptide Y(1)
      receptors, as well as brachial plexus blockade, on endothelium-dependent
      vasodilation in the human forearm.
AB  - 1. The aim of the present study was to investigate the effects of alpha
      adrenoceptor blockade (phentolamine), beta-adrenoceptor blockade (propranolol),
      neuropeptide Y(1) receptor blockade and neurogenic blockade (brachial plexus) on
      endothelium-dependent vasodilation (EDV) in the human forearm. 2. Forty-four
      young healthy volunteers underwent forearm blood flow (FBF) measurements, using
      venous occlusion plethysmography, during local intra-arterial infusions of
      methacholine (MCh; inducing EDV) and sodium nitroprusside (SNP; inducing
      endothelium-independent vasodilation (EIDV)). These measurements were undertaken
      at baseline and were repeated with either concomitant local intra-arterial
      infusion of phentolamine (n = 8), propranolol (n = 7) or saline (n = 6) in the
      forearm, neuropeptide Y(1) receptor blockade (n = 12) given i.v. or during
      axillary plexus blockade (n = 11). 3. Both alpha-adrenoceptor blockade and
      neurogenic blockade induced an upward shift in the dose-response curve for both
      EDV and EIDV. beta-Adrenoceptor blockade did not change resting FBF or EIDV, but
      induced a significant decrease in EDV (P = 0.015). Neuropeptide Y(1) receptor
      blocker induced no significant changes in resting FBF, EDV and EIDV and neither
      did saline. No changes in blood pressure or heart rate were induced by any of the
      blockades. 4. Whereas beta-adrenoceptor blockade impaired EDV, alpha-adrenoceptor
      blockade and neurogenic blockade caused a general vasodilation that was not
      endothelium dependent. Neuropeptide Y does not seem to influence blood flow in
      the resting forearm.

PMID- 12060103
TI  - Critical role of gap junctions in endothelium-dependent hyperpolarization in rat
      mesenteric arteries.
AB  - 1. Acetylcholine (ACh) evokes endothelium-dependent hyperpolarization in arterial
      cells, presumably through endothelium-derived hyperpolarizing factor (EDHF). The
      identity of EDHF is still elusive; however, several recent studies suggest the
      possible involvement of myoendothelial gap junctions in the EDHF response. 2. To
      elucidate the role of gap junctions in endothelium-dependent hyperpolarization,
      we examined the effects of the gap junction inhibitors 18 alpha-glycyrrhetinic
      acid (18 alpha-GA; 10(-4) mol/L) and carbenoxolone (3 x 10(-4) mol/L), a water
      soluble form of 18 beta-GA, on hyperpolarization and relaxation to ACh in rat
      proximal and distal mesenteric arteries. Experiments were performed in the
      presence of indomethacin (10(-5) mol/L) and N(G)-nitro-L-arginine (10(-4) mol/L).
      3. In both proximal and distal mesenteric arteries, ACh-induced hyperpolarization
      and relaxation were partially inhibited by 18 alpha-GA and abolished by
      carbenoxolone. 4. Endothelium-independent hyperpolarization to levcromakalim, an
      ATP-sensitive K+ channel opener, were unaffected by 18 alpha-GA or carbenoxolone
      in both arteries. 5. Relaxations to levcromakalim were unaffected by 18 alpha-GA,
      but were inhibited somewhat by carbenoxolone in proximal mesenteric arteries. 6.
      These findings suggest that myoendothelial gap junctions play a critical role in
      EDHF-mediated responses in both proximal and distal mesenteric arteries of the
      rat.

PMID- 12060105
TI  - Effects of endotoxin-induced shock on withdrawal contractions in the Guinea-pig
      isolated ileum.
AB  - 1. Taking into consideration the effect of septic shock on releasing various
      mediators, the present study was undertaken in an attempt to elucidate the effect
      of endotoxin on naloxone-induced withdrawal contractions in the guinea-pig
      isolated ileum. 2. To induce withdrawal contractions, preparations removed either
      from saline- or endotoxin (2.5 mg/kg in 0.4 mL, i.p.)-treated animals were
      incubated for 5 min with morphine (40 micromol/L) and naloxone (50 micromol/L)
      was then applied. 3. In tissues removed from endotoxin-treated animals, a
      significant reduction in withdrawal contractions was observed. In control
      preparations, indomethacin (1 micromol/L for 15 min) significantly reduced
      naloxone-induced contractions, whereas N(G)-nitro-L-arginine methyl ester (L
      NAME; 10 micromol/L for 15 min) had no effect. However, indomethacin pretreatment
      of tissues removed from endotoxin-treated animals did not modify the withdrawal
      contractions, whereas L-NAME pretreatment enhanced the amplitude of the
      withdrawal-induced contractions. 4. These results suggest that attenuation of the
      withdrawal contractions in guinea-pig isolated ileum induced by endotoxin
      pretreatment may be due, in part, to the activation of an L-arginine-nitric oxide
      pathway.

PMID- 12060106
TI  - Cellular signalling in arteriolar myogenic constriction: involvement of tyrosine
      phosphorylation pathways.
AB  - 1. An increase in transmural pressure in arterioles results in a shortening of
      vascular smooth muscle cells, with subsequent constriction of the vessel. The
      mechanisms underlying this myogenic contraction are not fully understood;
      however, the obligatory role of increases in intracellular [Ca(2+)] and myosin
      light chain phosphorylation have been demonstrated. 2. The myogenic response
      shows a relationship with smooth muscle cell membrane potential and influx of
      extracellular Ca(2+) through voltage-operated Ca(2+) channels (VOCC).
      Mechanically sensitive channels and possibly release of Ca(2+) from intracellular
      stores may play a role. However, there are other components of myogenic
      contraction that cannot be explained by a Ca(2+)-MLCK mechanism, for example the
      initial sensing of alterations in transmural pressure, whether sustained myogenic
      constriction involves myofilament Ca(2+) sensitization or remodelling of the
      vessel wall in response to a maintained increase in transmural pressure. 3. In an
      attempt to investigate these areas, recent studies have examined a role for
      tyrosine phosphorylation pathways in pressure-induced contraction of arterioles.
      In rat pressurized cremaster arterioles, tyrosine kinase inhibitors dilated
      vessels showing spontaneous myogenic tone and tyrosine phosphatase inhibitors
      caused vasoconstriction. However, pressure-induced myogenic constriction of
      vessels persisted in the presence of these agents. Biochemical studies revealed
      that phosphotyrosine formed at a relatively slow rate (significant after 5 min,
      with maximal increase after approximately 15 min) in response to increased vessel
      transmural pressure, in contrast with myosin light chain phosphorylation or the
      time-course of myogenic constriction itself (maximum within 1 min). 4. Taken
      together, these observations support the idea of a role for tyrosine
      phosphorylation pathways in longer-term responses to increased transmural
      pressure rather than acute myogenic constriction. Phosphotyrosine formation was
      also more closely correlated to vessel wall tension (pressure x diameter) than
      the diameter of the arterioles alone. The identity of the tyrosine-phosphorylated
      proteins requires further investigation; however, there is some evidence
      supporting roles for cSrc-type tyrosine kinases and p44 mitogen-activated protein
      kinase. The longer-term responses of blood vessels to increased transmural
      pressure that may involve tyrosine phosphorylation pathways include maintenance
      of myogenic constriction and vessel wall remodelling.

PMID- 12060107
TI  - Heterogeneity in the distribution of vascular gap junctions and connexins:
      implications for function.
AB  - 1. Gap junctions, which are comprised of members of a family of membrane proteins
      called connexins (Cx), permit the transfer of electrical and chemical information
      between adjacent cells in a wide variety of tissues. The aim of the present study
      was to compare the expression of Cx37, 40 and 43 in the smooth muscle and
      endothelium of a large elastic artery and two smaller muscular arteries of the
      rat. Serial section electron microscopy was also used to determine the presence
      of pentalaminar gap junctions in the smooth muscle and the incidence of
      myoendothelial gap junctions between the smooth muscle and endothelial cells in
      muscular arteries of different size. 2. Using immunohistochemistry, Cx37, 40 and
      43 were found in the endothelium of the aorta, caudal and basilar arteries, with
      Cx43 being the least abundant. Connexin 43 was readily observed throughout the
      muscle layers of the aorta, but was not detected in the media of the caudal or
      basilar arteries. Connexin 40 was not detected in the media of any of the
      arteries, while very fine punctate staining was observed with Cx37 antibodies in
      the media of the caudal and basilar arteries, but not in the aorta. 3. Real-time
      polymerase chain reaction showed that the expression of mRNA for Cx43 was 15-fold
      greater in the aorta than in the caudal artery of the rat. 4. At the
      ultrastructural level, small pentalaminar gap junctions (< 100 nm) were found
      between the fine processes of adjacent smooth muscle cells and also between the
      smooth muscle and endothelial cells. The incidence of myoendothelial gap
      junctions in the mesenteric vascular bed and in the caudal artery increased as
      vessel size decreased. 5. In summary, heterogeneity exists within the vascular
      system with regard to the distribution of gap junctions and their constituent Cx.
      Such variation will have important consequences for the coordination and
      propagation of vascular responses. In muscular arteries, in comparison with
      elastic arteries, Cx37 may be more important than Cx43 for cell coupling within
      the smooth muscle layers. The correlation between the incidence of myoendothelial
      gap junctions and the role of endothelium-derived hyperpolarizing factor,
      relative to nitric oxide, in vasodilatory responses suggests that myoendothelial
      gap junctions play an important physiological role in the regulation of vascular
      tone.

PMID- 12060108
TI  - Cellular coupling and conducted vasomotor responses.
AB  - 1. The present brief review examines the concept of spreading vasodilator
      responses in arteriolar trees, its physiological relevance and possible
      mechanisms. 2. The most likely mechanisms involve spread of hyperpolarization
      through tissues in the vessel wall, made possible by electrical coupling between
      the cells. It is generally agreed that there is coupling between cells within the
      muscle and endothelial layers, but coupling between the two layers is not always
      present. 3. The passive electrical properties of arterioles can be modelled,
      using different techniques depending on the complexity of branching of the
      arteriolar tree. Comparison of experimental results with the model indicates that
      hyperpolarization can spread further than expected from passive properties alone,
      implying that spreading vasodilatation may be an active process.

PMID- 12060109
TI  - Myoendothelial electrical coupling in arteries and arterioles and its
      implications for endothelium-derived hyperpolarizing factor.
AB  - 1. Considerable progress has been made over the past decade in evaluating the
      presence of electrical coupling between the endothelial and smooth muscle layers
      of blood vessels, prompted, in part, by ultrastructural evidence for the presence
      of myoendothelial junctions. 2. In a variety of vessels ranging in size from
      conduit arteries down to small arterioles, action potentials have been recorded
      from endothelial cells that were associated with constriction of the vessels
      and/or occurred in synchrony with and were indistinguishable from action
      potentials recorded from the smooth muscle. From these results, it is now firmly
      established that myoendothelial electrical coupling occurs in at least some blood
      vessels. 3. Spread of hyperpolarizing current from the endothelium to the smooth
      muscle is the most likely explanation of the smooth muscle hyperpolarization
      attributed to endothelium-derived hyperpolarizing factor. Because this
      hyperpolarization can evoke considerable relaxation of the smooth muscle,
      myoendothelial electrical coupling has important implications for endothelial
      regulation of the contractile activity of blood vessels.

PMID- 12060110
TI  - Bone marrow penicilliosis.

PMID- 12060111
TI  - Diabetes mellitus diagnosed following request for haemoglobin electrophoresis.

PMID- 12060113
TI  - Current trends in essential thrombocythaemia.

PMID- 12060112
TI  - Congenital erythropoietic porphyria: advances in pathogenesis and treatment.

PMID- 12060114
TI  - A corpse in law.

PMID- 12060115
TI  - Anaplastic large cell lymphoma in childhood: analysis of 72 patients treated on
      The United Kingdom Children's Cancer Study Group chemotherapy regimens.
AB  - From June 1990 to June 1998, 72 patients with anaplastic large cell lymphoma
      (ALCL) were treated with short intensive multi-agent regimens [non-Hodgkin's
      lymphoma (NHL) 9000 and 9602]. Diagnosis was based on morphological and
      immunophenotypic criteria. Treatment for stage I disease consisted of eight
      courses (2 x vincristine, doxorubicin, prednisolone; 2 x methotrexate; 2 x
      cytarabine, thioguanine; and 2 x methotrexate etoposide). For stage II, III and
      non-central nervous system (CNS) stage IV, two COPADM (cyclophosphamide,
      doxorubicin, prednisolone, methotrexate, vincristine), two CYM (cytarabine
      methotrexate) and a COPADM was given. For CNS-positive disease, treatment was
      intensified and contained methotrexate 8 g/m(2) and cytarabine 3 g/m(2). Fifty
      nine patients (82%) achieved a remission. Thirteen of these relapsed, with a
      median time to relapse from the start of treatment of 5 months (range 3-14).
      Relapse included a new site in 9/13 patients. The probabilities of overall and
      event free survival at 5 years were 65% (53-76%) and 59% (47-70%), respectively,
      with a median follow up of 4.3 years. Mediastinal and visceral involvement at
      presentation were found to be predictive of an increased risk of failure.

PMID- 12060116
TI  - Evidence that continued remission in patients treated for acute leukaemia is
      dependent upon autologous natural killer cells.
AB  - Although it has been known for more than 40 years that allogeneic immune
      responses cure leukaemias after bone marrow transplantation, autologous leukaemia
      specific immunity remains controversial and its impact upon survival has not been
      established. Here we have tested 25 patients with de novo acute leukaemias, while
      in remission at completion of their anti-leukaemia therapy, for evidence of
      autologous cytolytic immunity to their leukaemic cells taken and cryopreserved at
      disease presentation. We have measured this degree of cell-mediated cytotoxicity
      in vitro and termed it "leukaemia cytolytic activity" (LCA). Patients whose
      disease ultimately relapsed had significantly lower LCA than those who remained
      in remission beyond 2 years (P < 0.001); the absence of LCA when in remission
      predicted subsequent relapse within 2 years with a sensitivity of 100% and
      specificity of 77%. LCA was mediated in vitro by CD56+/CD8alpha+/CD3- natural
      killer cells. We propose that it is this immune response, rather than the
      chemotherapy per se, which is responsible for continued remission and that
      measurement of LCA in patients at completion of therapy may be used as an
      indicator of risk of subsequent relapse. Patients lacking this response will
      require further treatment, either with an allogeneic donor transplant or an
      alternative immunotherapeutic strategy.

PMID- 12060117
TI  - Combination immunotherapy with rituximab and interleukin 2 in patients with
      relapsed or refractory follicular non-Hodgkin's lymphoma.
AB  - Rituximab has significant activity as a single agent in the treatment of
      follicular non-Hodgkin's lymphoma (NHL). Interleukin 2 (IL-2) is a lymphokine
      that increases effector cell number. In an effort to augment antibody-dependent
      cell-mediated cytotoxicity (ADCC) associated with rituximab therapy, low-dose IL
      2 was added to a standard rituximab regimen and patients were evaluated for
      safety and efficacy. Twenty patients with relapsed or refractory follicular NHL
      were treated with IL-2 (1.2 MIU/m(2)/d for 56 d subcutaneously) as outpatients.
      Rituximab (375 mg/m(2)) was given on d 15, 22, 29 and 36. The regimen was well
      tolerated and only three patients required dose adjustments in IL-2. Infusional
      toxicity associated with rituximab was not exacerbated by IL-2. Peripheral blood
      immunophenotyping demonstrated significant increases in circulating CD8+ and
      CD56+ lymphocytes in all evaluable patients (P = 0.0002). Increases in total
      eosinophil number were observed in all patients. Eleven patients responded to
      therapy, for an overall response rate of 55%. Four additional patients had stable
      disease. For these 15 patients, the median time to progression exceeded 13
      months. We conclude concomitant cytokine therapy to enhance ADCC with monoclonal
      antibody therapy was well tolerated and did not exacerbate antibody-related
      infusional toxicity. Further studies of this rational combination are warranted
      and ongoing.

PMID- 12060118
TI  - Marrow matrix metalloproteinases (MMPs) and tissue inhibitors of MMP in acute
      leukaemia: potential role of MMP-9 as a surrogate marker to monitor leukaemic
      status in patients with acute myelogenous leukaemia.
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs) were demonstrated to have important implications in the progression and
      invasiveness of many malignant disorders. In contrast, the biological
      significance of these molecules in human leukaemias is not clear. We determined
      the levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 in the bone marrow of 37 patients
      with acute myelogenous leukaemia (AML) and 18 patients with acute lymphoblastic
      leukaemia (ALL) before chemotherapy. Nineteen bone marrow donors served as normal
      controls. After chemotherapy, sequential measurements were done during the course
      in 19 AML patients. The levels of TIMP-1 and TIMP-2 were significantly higher and
      MMP-9 levels were significantly lower in the AML and ALL patients than in the
      normal controls. MMP-2 levels were higher in ALL, but not AML patients, compared
      with controls. Moreover, the levels of marrow MMP-2 and MMP-9 did not parallel
      the numbers of leukaemic blasts in the peripheral blood. MMP-9 levels were
      significantly lower in the AML patients who achieved a complete remission (CR)
      than in those who did not (8.71 +/- 8.15 ng/ml vs 26.13 +/- 27.75 ng/ml, P <
      0.05). The AML patients with lower MMP-9 levels (< or = 4.4 ng/ml) tended to have
      longer survival time than those with higher levels (> 12 months vs 4 months, P =
      0.12). In addition, MMP-9 levels in the AML patients at CR rose to the same range
      as the controls, but dropped again at relapse, demonstrating a close relationship
      of marrow MMP-9 with disease status of AML. Therefore, we conclude that the level
      of marrow MMP-9 may be a useful surrogate marker for monitoring disease status in
      AML and propose it as a potential prognostic factor.

PMID- 12060119
TI  - Analysis of resveratrol-induced apoptosis in human B-cell chronic leukaemia.
AB  - Trans-resveratrol was analysed for its apoptotic and growth inhibitory activity
      in human B-cell lines derived from chronic B-cell malignancies (WSU-CLL and
      ESKOL), and in leukaemic lymphocytes from patients with B-cell chronic
      lymphocytic leukaemia (B-CLL). Resveratrol displayed antiproliferative activity
      on both B-cell lines, as estimated by the decrease in cell recovery and
      inhibition of thymidine uptake. Furthermore, resveratrol induced apoptosis in the
      two cell lines as well as in B-CLL patients' cells, as evidenced by the increase
      in annexin V binding, caspase activation, DNA fragmentation and decrease of the
      mitochondrial transmembrane potential DeltaPsim. We previously reported that
      nitric oxide (NO), endogenously released by an iNO synthase (iNOS) spontaneously
      expressed in these leukaemic cells, contributed to their resistance towards
      apoptosis. We show here that resveratrol inhibited both iNOS protein expression
      and in situ NO release in WSU-CLL, ESKOL and B-CLL patients'cells. In addition,
      Bcl-2 expression was also inhibited by resveratrol. Thus, downregulation of the
      two anti-apoptotic proteins iNOS and Bcl-2 can contribute to the apoptotic
      effects of resveratrol in leukaemic B cells from chronic leukaemia. Our data
      suggest that this drug is of potential interest for the therapy of B-CLL.

PMID- 12060120
TI  - Chromosomal aberrations are shared by malignant plasma cells and a small fraction
      of circulating CD19+ cells in patients with myeloma and monoclonal gammopathy of
      undetermined significance.
AB  - In the present study, we aimed to identify distinct structural and numerical
      chromosomal aberrations in peripheral blood B cells of patients with myeloma and
      monoclonal gammopathy of undetermined significance (MGUS), which reflect changes
      thought to occur at different stages of the disease process. Peripheral blood
      from 12 patients with multiple myeloma and three patients with MGUS was
      investigated for the occurrence of retinoblastoma-1 gene deletions, p53 gene
      deletions and numerical aberrations demonstrated previously to be present in the
      patients' bone marrow CD138+ cells. By combining immunocytochemical staining for
      light chains and interphase fluorescence in situ hybridization (FISH), aberrant
      light-chain +ve cells were detected in the circulating CD19+ cell fraction. Each
      kind of chromosomal change present in the myeloma tumour cells was found to be
      shared by a small fraction of CD19+ cells (0.1-1.8%; median 0.36%, n = 6). In one
      MGUS patient, aberrant cells could be identified with a frequency of 0.34% within
      the CD19-sorted cell fraction. Clonotypic cells were detected with a frequency of
      0.01-0.07% of peripheral blood nucleated cells by m-RNA in situ hybridization
      with patient-specific probes in three investigated patients. These results
      provide evidence that the circulating clonotypic B cells are closely related to
      the malignant plasma cells in myeloma and MGUS.

PMID- 12060121
TI  - In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia.
AB  - Factors that reduce the intracellular concentration of triphosphorylated
      cytarabine (ara-CTP), the active form of cytarabine (ara-C), may induce
      chemoresistance in acute myeloid leukaemia (AML) patients. These factors include
      reduced influx of ara-C by the hENT1 transporter, reduced phosphorylation by
      deoxycytidine kinase (dCK), and increased degradation by high Km cytoplasmic 5'
      nucleotidase (5NT) and/or cytidine deaminase (CDD). Increased levels of DNA
      polymerase alpha (DNA POL) and reduced levels of topoisomerase I (TOPO I) and
      topoisomerase II (TOPO II) have also been detected in ara-C-resistant cell lines.
      To determine whether these factors are implicated in clinical ara-C resistance,
      we analysed the expression of these parameters at diagnosis, using reverse
      transcription polymerase chain reaction, in the blast cells of 123 AML patients
      treated with ara-C. At diagnosis, hENT1, dCK, CDD, 5NT, TOPO I, TOPO II, DNA POL
      and MDR1 were expressed in 83%, 22%, 7%, 37%, 59%, 37%, 39% and 16% of patients
      respectively. In univariate analysis, patients with expression of 5NT or DNA POL
      at diagnosis had significantly shorter disease-free survival (DFS). In
      multivariate analysis, DNA POL positivity and hENT1 deficiency were related to a
      shorter DFS. In univariate analysis, patients with 5NT-positive blasts had
      significantly shorter overall survival (OS). In multivariate analysis, shorter OS
      was related to DNA POL positivity. These results suggest that expression of DNA
      POL, 5NT and hENT1 at diagnosis may be resistance mechanisms to ara-C in AML
      patients.

PMID- 12060122
TI  - Time to platelet recovery predicts outcome of patients with de novo acute
      lymphoblastic leukaemia who have achieved a complete remission.
AB  - Survival in acute leukaemia depends on the achievement of complete remission
      (CR). However, CR is not a clear-cut phenomenon and certain variables of its
      definition could more accurately characterize the quality of the remission.
      Because platelet recovery > 100 x 10(9)/l is an essential component of CR in
      acute leukaemia, we hypothesized that time to platelet recovery (TPR) might be
      predictive of overall survival (OS) or disease-free survival (DFS) in acute
      lymphoblastic leukaemia (ALL). We analysed TPR in 249 patients with ALL who
      entered CR after one course of induction chemotherapy and correlated TPR with DFS
      and OS. TPR was significantly associated with both DFS and OS if it occurred
      within a maximum of about 60 d from start of therapy. Furthermore, during that
      time period, the relative risk of death increased with increasing TPR. Although
      presence of the Philadelphia chromosome was the single most important adverse
      feature at diagnosis, the effect of TPR on survival continued to be significant
      within this patient subgroup. This effect was so pronounced that Philadelphia
      chromosome-positive patients with a TPR of 12 d had a better outcome than
      Philadelphia chromosome-negative patients with a TPR of 48 d. Thus, a short TPR
      seems to be able to override adverse characteristics in the outcome of ALL
      patients treated with chemotherapy. We conclude that a quicker TPR predicts
      longer DFS and OS in patients with ALL. As platelet counts are obtained almost
      daily in patients undergoing chemotherapy, TPR can readily be utilized to assess
      the prognosis of these patients.

PMID- 12060123
TI  - Dual transcription of b2a2 and b3a2 BCR-ABL transcripts in chronic myeloid
      leukaemia is confined to patients with a linked polymorphism within the BCR gene.
AB  - We propose a mechanism for dual expression of b2a2 and b3a2 BCR-ABL in chronic
      myeloid leukaemia (CML). We have identified a BCR allele, present in
      approximately 29% of the population, which includes an adenine to guanine
      polymorphism in the putative branchpoint of BCR intron 13. CML patients who
      expressed both b2a2 and b3a2 transcripts had the allele, which was also
      associated with alternative transcription of the normal BCR allele. We conclude
      that the BCR intronic polymorphism is associated with activation of a cryptic
      branchpoint resulting in reduced efficiency of RNA splicing and exon 14 (b3)
      skipping in BCR and BCR-ABL.

PMID- 12060124
TI  - A novel inherited mutation of the transcription factor RUNX1 causes
      thrombocytopenia and may predispose to acute myeloid leukaemia.
AB  - The RUNX1 (AML1, CBFA2) gene is a member of the runt transcription factor family,
      responsible for DNA binding and heterodimerization of other non-DNA binding
      transcription factors. RUNX1 plays an important part in regulating haematopoiesis
      and it is frequently disrupted by illegitimate somatic recombination in both
      acute myeloid and lymphoblastic leukaemia. Germline mutations of RUNX1 have also
      recently been described and are dominantly associated with inherited leukaemic
      conditions. We have identified a unique point mutation of the RUNX1 gene (A107P)
      in members of a family with autosomal dominant inheritance of thrombocytopenia.
      One member has developed acute myeloid leukaemia (AML).

PMID- 12060125
TI  - Clinicopathological and prognostic characteristics of CD56-negative multiple
      myeloma.
AB  - We analysed CD56 expression in 70 patients with multiple myeloma (MM) to
      determine its clinicopathological and prognostic significance. Fifty-five (79%)
      patients were CD56+. CD56- patients (n = 15) had higher beta2 microglobulin
      levels and a higher incidence of extramedullary disease, Bence Jones protein,
      renal insufficiency and thrombocytopenia than CD56+ patients. Their myelomas more
      frequently had a plasmablastic morphology. Overall survival was significantly
      lower in CD56- than CD56+ patients (22 vs 63 months, P = 0.0002). We conclude
      that CD56- MM is a discrete entity associated with more aggressive disease. The
      higher incidence of plasmablastic cases suggested that CD56- MM may develop from
      a less mature plasma cell than CD56+ MM.

PMID- 12060126
TI  - Low-dose continuous oral melphalan for the treatment of primary systemic (AL)
      amyloidosis.
AB  - Median survival of patients with AL amyloidosis with clinically significant
      cardiac involvement is 5 months when treated with cyclic melphalan and
      prednisone. We investigated a regimen of continuous oral melphalan as a single
      agent for patients with cardiac amyloidosis who were unable to tolerate
      prednisone or more aggressive chemotherapy. Thirty patients with amyloid
      cardiomyopathy were treated with continuous oral melphalan. Seven of 13 patients,
      evaluable after 3-4 months of treatment, achieved a partial haematological
      response and three achieved a complete haematological response; six patients have
      survived for > 1 year. This regimen appeared to be effective in inducing
      haematological responses in patients who received total doses of melphalan > 300
      mg.

PMID- 12060127
TI  - Methylenetetrahydrofolate reductase genotype does not play a role in multiple
      myeloma pathogenesis.
AB  - Methylenetetrahydrofolate reductase (MTHFR) plays an important role in
      carcinogenesis. A decreased incidence of cancer has been reported in the presence
      of MTHFR 677TT, 1298AC and 1298CC polymorphic variants. We have analysed the
      MTHFR genotype in 107 multiple myeloma (MM) patients and 86 controls. The MM and
      control polymorphisms frequencies were: 34% and 48% for 677CC, 53% and 41% for
      677CT, 12% and 11% for 677TT; 36% and 43% for 1298AA, 51% and 44% for 1298AC; and
      12% and 13% for 1298CC respectively. No statistically significant differences
      were observed. In addition, no differences were seen according to MM stage,
      presence of p16 gene hypermethylation or response to treatment.

PMID- 12060128
TI  - Human leucocyte antigen-Cw-specific cytotoxic T lymphocytes generated from naive
      cord blood used for cord blood stem cell transplantation.
AB  - Human leucocyte antigen (HLA)-Cw-reactive cytotoxic T lymphocytes (CTL) were
      generated from cord blood (CB) lymphocytes of two cases used for cord blood stem
      cell transplantation (CBSCT). In both cases, the CTL were cytotoxic against the
      patient's leukaemic cells, as well as the patient's Epstein-Barr virus (EBV)
      lymphoblastoid cell line (EBV-LCL) and phytohaemagglutinin blasts, and the
      cytotoxicity was blocked by anti-HLA-class I monoclonal antibodies. In the first
      case, the CTL recognized Cw 3 (Cw 9 and Cw 10)-positive EBV-LCL, while in the
      second case, the CTL recognized Cw1 and/or Cw7. These cases suggest that CB T
      cells may be competent enough for generating CTL to induce a graft-versus
      leukaemia effect and/or graft-versus-host disease in patients with CBSCT and that
      the mismatching of Cw antigens between patient and CB may be related to the
      outcome of CBSCT.

PMID- 12060129
TI  - T-cell immune constitution after peripheral blood mononuclear cell
      transplantation in complete DiGeorge syndrome.
AB  - Complete DiGeorge syndrome (cDGS) is a congenital disorder characterized by
      typical facies, thymic aplasia, susceptibility to infections, hypoparathyroidism
      and conotruncal cardiac defect. Fetal thymus or post-natal thymus tissue
      transplantations and human leucocyte antigen (HLA)-genoidentical bone marrow
      transplantations were followed in a few cases by immune reconstitution. More
      recently, a peripheral blood mononuclear cell transplantation (PBMCT) was
      performed with an HLA-genoidentical donor and followed by a partial T-cell
      engraftment and immune reconstitution. We report a boy with cDGS, without cardiac
      defect, who suffered recurrent severe infections. At the age of 4 years, he
      underwent PBMCT from his HLA-genoidentical sister. He received no conditioning
      regimen, but graft-versus-host disease (GVHD) prophylaxis was with oral
      cyclosporin A and mycophenolate mofetil. Toxicity was mild, with grade I acute
      GVHD. The patient is currently 2.5 years post-PBMCT with excellent clinical
      performances. Mixed chimaerism can only be observed on the T-cell population (50%
      donor T cells). T-lymphocyte count fluctuated (CD3 more than 400 x 10(6)/l at d
      84 and CD4 more than 200 x 10(6)/l at d 46). Exclusive memory phenotype T cells
      and absence of new thymic emigrants suggest expansion of infused T cells. T-cell
      mitogen and tetanus antigen responses normalized a few months after
      transplantation. After immunizations, specific antibodies were produced. PBMCT
      from an HLA identical sibling could be an efficient treatment of immune
      deficiency in cDGS.

PMID- 12060130
TI  - Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purging
      for acute myeloid leukaemia beyond first remission: a 10-year experience.
AB  - Between January 1987 and January 1997, 69 eligible patients with acute myeloid
      leukaemia (AML) in either second (CR2) or third (CR3) complete remission (CR2 =
      60, CR3 = 9) underwent 4-hydroperoxycyclophosphamide-purged autologous bone
      marrow transplantation (BMT) at the Johns Hopkins Oncology Center. The patients'
      median age was 27 years (range 1-62) and all received busulphan and
      cyclophosphamide as their preparative regimen. The probability of event-free
      survival (EFS) at 5 years was 30% [95% Confidence Interval (CI): 19-42%] for CR2
      patients and 22% (3-51%) for those in CR3, with a median follow up of 8 years in
      the surviving group. The median time to an absolute neutrophil count of 0.5 x
      109/l was 45 d (range 20-185). Relapse was the major cause of failure with a
      relapse rate of 55% in CR2 and 44% in CR3, while the non-relapse, transplant
      related mortality rate was 15% in CR2 and 33% in CR3. In univariate analysis,
      patient age, cytogenetics, white blood cell count at presentation, CR1 duration
      and the sensitivity of clonogeneic leukaemia (CFU-L) in the graft to 4HC were all
      prognostic for EFS. Using each of these significant variables in multivariate
      modelling, patient age and sensitivity of CFU-L to 4HC were determined to be
      predictors of EFS. 4HC-purged autologous BMT produced results similar to
      allogeneic BMT for AML patients beyond first remission.

PMID- 12060131
TI  - Factors affecting long-term outcome after allogeneic haematopoietic stem cell
      transplantation for acute myelogenous leukaemia: a retrospective study of 172
      adult patients reported to the Austrian Stem Cell Transplantation Registry.
AB  - Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML)
      received haematopoietic stem cell transplants (SCT) from related (n = 132) or
      unrelated (n = 40) donors at four Austrian transplant centres and their results
      were reported to the Austrian Stem Cell Transplantation Registry. Conditioning
      for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%)
      patients. Graft-versus-host disease (GVHD) prophylaxis was with standard
      cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow
      up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related
      mortality (TRM) identified four variables associated with a lower risk: disease
      status of first complete remission (CR) at SCT, patient age of 45 years and
      younger, transplant performed during or after 1995, and lack of acute GVHD.
      Variables associated with significantly improved leukaemia-free survival were:
      bone marrow as the stem cell source, disease status of first CR at SCT, and
      occurrence of chronic GVHD. In multivariate analysis, transplantation performed
      during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and
      lack of acute GVHD grades III to IV were associated with increased overall
      survival. Based on these analyses, options for the improvement of results
      obtained with allogeneic SCT in patients with AML could be defined.

PMID- 12060132
TI  - Ex vivo expansion marginally amplifies repopulating cells from baboon peripheral
      blood mobilized CD34+ cells.
AB  - The ability of ex vivo expansion to increase the long-term repopulating capacity
      of a graft is still unknown. One problem is the most reliable way to quantify
      transplantable cells. We addressed this point in a baboon model based on
      autologous transplantation of serial limiting doses of non-manipulated or ex vivo
      expanded mobilized CD34+ cells and determined the threshold doses of non
      manipulated and expanded cells which supported long-term multilineage
      engraftment. In the expansion group, CD34+ cells were cultured for 6 d with a
      combination of early acting cytokines (Flt3-ligand, stem cell factor,
      thrombopoietin and interleukin 3). Grafted cells were characterized by their
      surface antigens and biological properties [semisolid assays, long-term culture
      initiating cells (LTC-IC) and non-obese diabetic severe combined immunodeficient
      reconstituting cells (SRC)]. Animals were followed for at least 12 months post
      transplantation. The expansion protocol yielded 12.3-fold, 16.9-fold, 3.7-fold,
      3.5-fold and 2.2-fold increases in CD34+ cells, granulocyte-macrophage colony
      forming units (CFU-GM), megakaryocyte CFU (CFU-MK), LTC-IC and SRC respectively.
      It induced a modest increase in the long term reconstitutive ability of the
      graft; the threshold value for long-term engraftment was 0.5 x 10(6)/kg CD34+
      cells in the control group and 0.3 x 10(6)/kg CD34+ cells in the expansion group,
      although one animal in this latter group remained hypoplastic. Frequencies of SRC
      had a high predictive value of long-term engraftment (r > 0.80). The main
      advantage of the protocol was the acceleration of granulocyte recovery, achieved
      at the different doses tested. In conclusion, these experiments suggest that this
      ex vivo expansion protocol marginally amplifies long-term reconstituting cells.

PMID- 12060133
TI  - Induction of HA-1-specific cytotoxic T-cell clones parallels the therapeutic
      effect of donor lymphocyte infusion.
AB  - Donor lymphocyte infusions (DLI) can induce a graft-versus-leukaemia (GvL)
      reaction in patients with relapsed disease. However, the mechanisms involved in
      remission induction are not completely known. A patient with chemotherapy
      refractory relapse 1 year after human leucocyte antigen (HLA)-identical,
      unrelated stem cell transplantation (SCT) for bcr/abl-positive common acute
      lymphoblastic leukaemia (ALL) received a DLI from the original donor, and
      achieved complete cytogenetic and molecular remission concomitantly with
      extensive graft-versus-host disease (GvHD). Seven CD8+, donor-derived,
      alloreactive T-cell clones were generated by stimulating post-DLI remission cells
      with the patient's pretransplant mature dendritic cells. The minor
      histocompatibility antigen (mHag) recognized by these T-cell clones was
      identified as HA-1, a mHag associated with acute GvHD after SCT. Our finding
      provides evidence of HA-1-associated GvL effects after DLI that paralleled the
      eradication of full-blown, chemotherapy-refractory ALL relapse after allogeneic
      SCT.

PMID- 12060134
TI  - Therapeutic quality control of oral anticoagulant therapy comparing the short
      acting acenocoumarol and the long-acting phenprocoumon.
AB  - To investigate whether the different pharmacokinetics of acenocoumarol (t(1/2) =
      11 h) and phenprocoumon (t(1/2) = 140 h) result in a different quality of
      anticoagulation, we studied patients from the Leiden anticoagulation clinic
      treated between 1998 and 1999 for more than 16 weeks. Two hundred and twenty
      eight pairs were closely matched for indication for oral anticoagulant therapy
      (OAT), age, sex and date of start of treatment. Four hundred and fifty six
      patients with 7245 International Normalized Ratio (INR) checks yielded 230
      patient-years. Quality of OAT calculated over the whole treatment period was
      higher with phenprocoumon as expressed by the number of INR checks in the
      therapeutic range (phenprocoumon: 42.7%, acenocoumarol: 36.5%, difference: 6.1%,
      CI(95) of the difference: 3.0-9.3%) and by time in range (phenprocoumon: 46.6%,
      acenocoumarol: 41.6%, difference: 5.0%, CI(95) of the difference: 1.3-8.6%).
      After the initial 6 weeks of OAT, the differences became more pronounced
      (difference: 6.1%, CI(95): 1.8-10.4%). The incidence of severe bleeding
      complications was similar (phenprocoumon: 0.04/patient/year vs acenocoumarol:
      0.03/patient/year) with a slight excess of minor bleeds with phenprocoumon
      (0.19/patient/year vs 0.06/patient/year). We conclude that phenprocoumon leads to
      a better quality of OAT than acenocoumarol. As there is no difference in major
      bleeding complications and only a small difference in minor bleeding
      complications, phenprocoumon is preferable to acenocoumarol for prolonged OAT.

PMID- 12060135
TI  - DDAVP challenge tests in boys with mild/moderate haemophilia A.
AB  - Desmopressin (DDAVP) increases plasma factor VIII coagulant activity (FVIII:C)
      levels in patients with mild/moderate haemophilia A. In some subjects, FVIII can
      be increased to haemostatic levels, thereby avoiding use of factor VIII
      concentrates. We reviewed our hospital's experience with 62 boys with FVIII:C
      levels 0.01-0.3 IU/ml who had a DDAVP challenge test (i.v. 0.3 microg/kg)
      following diagnosis. A therapeutic response was defined as a 1 h post-FVIII:C
      increase at least twofold over baseline and > 0.3 IU/ml. Of the total group, 29
      (47%) boys responded to DDAVP, all of them with mild haemophilia (baseline
      FVIII:C > or = 0.05 IU/ml), yielding a response rate of 57% in this subgroup.
      Boys who responded to DDAVP had higher baseline FVIII:C levels (mean +/- SEM,
      0.17 +/- 0.01 vs 0.10 +/- 0.01 IU/ml, P < 0.01) and were older (5.2 +/- 0.8 vs 3
      +/- 0.4 years, P = 0.02) than those who failed to do so. The association between
      DDAVP response and age, however, remains unclear: seven boys who failed the
      initial challenge test responded to re-challenge after a mean of 6.3 years
      (median 4.9, range 0.5-12.5), increasing the response rate in boys with mild
      haemophilia to 71%. Age and FVIII:C association with DDAVP response are both
      important in boys with mild/moderate haemophilia A. Absence of response to DDAVP
      should therefore be confirmed by later re-challenge.

PMID- 12060136
TI  - Liver transplantation in haemophilia.
AB  - We report our UK single-centre experience of liver transplantation in haemophilia
      patients with chronic hepatitis C (HCV) infection. Between March 1990 and March
      2001, 16 patients were referred for transplant assessment and 11 (mean age 46
      years: nine haemophilia A, two haemophilia B) have been transplanted. Factor
      concentrate replacement was administered using a continuous infusion regimen
      following initial bolus dosing. Concentrate infusion was discontinued at a median
      of 36 h (range 24-72 h) post transplant. Nine patients remain alive at a median
      of 5 years post transplant (6 months to 11 years). One patient died 6 years post
      transplant from myocardial infarction. The other patient died of liver failure as
      a consequence of HCV infection 3 months following a second transplant, having
      developed HCV cirrhosis within 1 year of receiving his initial graft. Five of the
      seven patients who have had annual liver biopsy surveillance have developed
      histological changes of HCV hepatitis at a median of 3 years post transplant (1
      year to 9 years). One of these patients progressed to cirrhosis at 3 years 5
      months post transplant. Two patients have shown no evidence of HCV hepatitis at 2
      years 8 months and 9 years post transplant respectively. The outcome of liver
      transplantation in haemophilic patients is good and is associated with relatively
      little morbidity.

PMID- 12060137
TI  - Activation profiles of factor VIII in concentrates reflect one-stage/chromogenic
      potency discrepancies.
AB  - We have investigated the possibility that differences in the profile of factor
      VIII (FVIII) activation, by thrombin, may help to explain the one
      stage/chromogenic potency discrepancies in two therapeutic concentrates. A Method
      M concentrate and a recombinant B-domain-deleted (B-DD) concentrate were found to
      have one-stage/chromogenic ratios of approximately 1.15 and 0.70, respectively,
      relative to the World Health Organization (WHO) 6th International Standard (IS)
      FVIII concentrate, whether pre-diluted in FVIII-deficient plasma or buffer (+/-
      von Willebrand factor, VWF). The activation of FVIII, by thrombin, was followed
      in a buffer medium (+/- VWF) and all three concentrates showed similar times to
      reach peak FVIII coagulation (FVIII:C) activity. However, despite the use of
      equivalent amounts of FVIII:C for all three concentrates, the B-DD concentrate
      reached a higher peak level and maintained higher FVIII:C compared with the WHO
      6th IS throughout the incubation period, whereas the Method M concentrate reached
      a lower peak level and maintained lower FVIII:C throughout the incubation period.
      We propose that the higher levels of FVIII:C found with the B-DD concentrate and
      the lower levels with the Method M concentrate, following activation, may be
      reflected in the potencies obtained by the chromogenic method and may be
      consistent with one-stage/chromogenic ratios of < 1.0 and > 1.0 respectively.

PMID- 12060138
TI  - Assessment of thrombocytopenic disorders using the Platelet Function Analyzer
      (PFA-100).
AB  - The Platelet Function Analyzer (PFA-100) was used to measure platelet function in
      paediatric patients with destructive versus underproduction thrombocytopenia.
      Closure time (CT) and total volume (TV) measurements with standard 150 microm
      apertures discriminated between patients with similar platelet counts from 30 to
      150 x 10(9)/l. However, at platelet counts < 30 x 10(9)/l, a 100-microm aperture
      (experimental) gave the best assessment of platelet function. TV results could be
      analysed even when CTs were indeterminate. Further investigations are warranted
      to more fully understand the relationships among platelet function as measured by
      the PFA-100 in standard/experimental modes, bleeding and transfusion outcome in
      thrombocytopenia.

PMID- 12060139
TI  - Functional consequences of perforin gene mutations in 22 patients with familial
      haemophagocytic lymphohistiocytosis.
AB  - Familial haemophagocytic lymphohistiocytosis (FHL), an inherited form of
      haemophagocytic lymphohistiocytosis (HLH) syndrome, is characterized by the
      overwhelming activation of T lymphocytes and macrophages invariably leading to
      death in the absence of treatment. FHL is a heterogeneous autosomal recessive
      disorder, with one known causative gene which codes for perforin, a cytotoxic
      effector protein. In this study, we have characterized the genotype and phenotype
      of 14 unrelated families with perforin deficiency. Four new missense mutations of
      the perforin gene were identified. In every case, perforin gene mutations led to
      undetectable intracellular perforin expression within cytotoxic cells, while some
      residual T-cell cytotoxic activity could be associated with certain missense
      mutations. Clinical and biological analyses did not differentiate between
      patients with nonsense or missense mutations, although age at diagnosis, which
      tended to be similar within members of the same family, was delayed in patients
      from two families belonging to the second group. In one case, consequences of
      perforin deficiency, diagnosed at birth, could be assessed prior to onset of
      clinical manifestations. No evidence for T-cell activation could be shown,
      suggesting that an exogenous event is required to trigger the disease
      manifestation. Control assessment of perforin expression and cytotoxic assays by
      lymphocytes from young children led to the conclusion that perforin content of
      natural killer cells could be a reliable diagnostic test at any age. Altogether,
      these data enabled a better characterization of perforin deficiency and its
      consequences, and defined reliable diagnostic tools.

PMID- 12060141
TI  - Congenital erythropoietic porphyria: identification and expression of eight novel
      mutations in the uroporphyrinogen III synthase gene.
AB  - Mutations in the uroporphyrinogen III synthase (URO-synthase) gene cause
      congenital erythropoietic porphyria (CEP), an autosomal recessive inborn error of
      haem biosynthesis. Molecular analysis of the URO-synthase gene in seven unrelated
      CEP patients revealed eight novel mutations. These included four missense
      mutations (A69T, E81D, G188W and I219S), a deletion (21delG), two insertions
      (398insG and 672ins28) and one complex mutation (627del6ins39), as well as three
      previously reported mutations, C73R, T228M, and -86C-->A. When the four novel
      missense mutations were expressed in Escherichia coli, only E81D expressed
      significant enzymatic activity (30% of expressed wild-type activity), which was
      thermolabile. In addition, reverse transcription polymerase chain reaction
      studies demonstrated that E81D, which altered the penultimate nucleotide in exon
      4, impaired splicing and caused about 85% exon 4 skipping. The identification and
      expression of these mutations provided genotype-phenotype correlations and
      further evidence of the molecular heterogeneity underlying this erythropoietic
      porphyria.

PMID- 12060140
TI  - Natural history of juvenile haemochromatosis.
AB  - Juvenile haemochromatosis or haemochromatosis type 2 is a rare autosomal
      recessive disorder which causes iron overload at a young age, affects both sexes
      equally and is characterized by a prevalence of hypogonadism and cardiopathy.
      Patients with haemochromatosis type 2 have been reported in different ethnic
      groups. Linkage to chromosome 1q has been established recently, but the gene
      remains unknown. We report the analysis of the phenotype of 29 patients from 20
      families of different ethnic origin with a juvenile 1q-associated disease. We
      also compared the clinical expression of 26 juvenile haemochromatosis patients
      with that of 93 C282Y homozygous males and of 11 subjects with haemochromatosis
      type 3. Patients with haemochromatosis type 2 were statistically younger at
      presentation and had a more severe iron burden than C282Y homozygotes and
      haemochromatosis type 3 patients. They were more frequently affected by
      cardiopathy, hypogonadism and reduced glucose tolerance. In contrast cirrhosis
      was not statistically different among the three groups. These data suggest that
      the rapid iron accumulation in haemochromatosis type 2 causes preferential tissue
      damage. Our results clarify the natural history of the disease and are compatible
      with the hypothesis that the HFE2 gene has greater influence on iron absorption
      than other haemochromatosis-associated genes.

PMID- 12060142
TI  - A wider molecular spectrum of beta-thalassaemia in Myanmar.
AB  - Two hundred and nine beta-thalassaemia (beta-Thal) alleles of 158 unrelated
      Myanmar patients (107 HbE-beta-Thal; 51 beta-Thal major) were analysed for beta
      globin gene mutations. Amplification refractory mutation system (ARMS)
      characterized six beta-thal mutations known to Myanmar [betaIVSI-1(G-->T), codon
      41/42(-TCTT), betaIVSI-5(G-->C), codon 17(A-->T), betaIVS II-654(C-->T), and -28
      Cap (A-->G)] in 166/209 (79.4%) alleles. DNA sequencing of 24 alleles from 43
      ARMS-negative samples (20.6%) identified an additional 12 new mutations, to
      produce a total of 18 different mutations. Nineteen alleles (9.1%) remained for
      further characterization. The molecular spectrum of Myanmar beta-Thal is wider
      and more heterogeneous than previously reported.

PMID- 12060143
TI  - Massive apoptosis of bone marrow cells in aplastic anaemia.

PMID- 12060144
TI  - Post-transfusion purpura without detectable antibodies: their adsorption from the
      plasma by multiple incompatible platelet transfusions.

PMID- 12060145
TI  - Hepatosplenic gammadelta T-cell lymphoma: complete response induced by treatment
      with pentostatin.

PMID- 12060146
TI  - Efficacy of thalidomide in the treatment of VAD-refractory plasma cell leukaemia
      appearing after autologous stem cell transplantation for multiple myeloma.

PMID- 12060147
TI  - Red cell lifespan estimation by (51)Cr labelling.

PMID- 12060148
TI  - Treatment of primary chronic cold agglutinin disease with rituximab: maintenance
      therapy may improve the results.

PMID- 12060152
TI  - Radiographic imaging procedures in the diagnosis of the major central
      neuropathological consequences of alcohol abuse.
AB  - Excessive consumption of alcohol is well recognized to have specific neurologic
      sequelae. The MRI and CT findings in these syndromes is presented and correlated
      with pathological findings and suspected pathogenesis. The role of imaging in
      both the diagnosis and monitoring of patients is discussed.

PMID- 12060153
TI  - Current status of positron emission tomography in oncology.
AB  - Positron emission tomography (PET) has emerged as a powerful diagnostic tool in
      oncology patients. There is evidence of the superior utility over conventional
      imaging methods of the principal PET tracer 18F-fluoro-2-deoxy-glucose in the
      staging of a range of cancers and monitoring disease recurrence, as well as
      changing patient management to more appropriate therapy. The methods for
      evaluating the evidence for PET remain complex, particularly as the standard
      evidence-based approach of randomized controlled trials is not generally
      applicable to imaging technologies. PET has the potential to dramatically improve
      our ability to manage patients with cancer and is also making major contributions
      to the development of new therapies.

PMID- 12060154
TI  - Computed tomography fluoroscopy-guided chemical lumbar sympathectomy: simple,
      safe and effective.
AB  - Demographic, clinical and laboratory data were retrospectively collected from
      records of 146 cases of CT fluoroscopy-guided chemical lumbar sympathectomy for
      the palliation of inoperable peripheral vascular disease (PVD) between January
      1997 and August 1999. Of these, 16% had claudication, 39% had rest pain and 44%
      had ischaemic ulcers or gangrene. Seventy-three percent of elective cases were
      outpatients. At 3 months, 27 cases were lost to follow up, leaving 119 cases.
      Within 3 months, improvement, defined as doubling of the walking distance,
      cessation of rest pain or healing of ulcers, occurred in 30.3% of cases. No
      change was observed in 45.4% of cases and 24.3% of cases deteriorated. Patients
      with ulcers or gangrene had significantly poorer results than those without any
      ischaemic lesions, as only 19% versus 39% of patients improved (P < 0.05). The
      presence of hypertension, diabetes mellitus, hyperlipidaemia and smoking had no
      value in predicting clinical outcome (P > 0.05). There were no major
      complications noted. CT fluoroscopy-guided chemical lumbar sympathectomy is safe
      and effective, with a complication rate of less than 1%, and efficacy of at least
      30% measured within 3 months. It is a simple and minimally invasive procedure,
      easily performed on an outpatient basis. CT fluoroscopy-guided chemical lumbar
      sympathectomy should be considered for all patients in the early stages of
      inoperable PVD.

PMID- 12060155
TI  - Evaluation of the effectiveness of digital radiography in emergency situations.
AB  - The time differences between digital and conventional radiography for emergency
      patients were investigated, and clinician satisfaction with the two modalities
      was compared. Time-motion data was collected daily over 5 weeks for a digital
      group and a conventional X-ray group. For standardization purposes, only
      emergency patients requiring chest X-rays were selected for the study. Data were
      collected from 30 patients in each of the two groups in the time-motion study,
      and 31 out of 50 Emergency and Intensive Care clinicians responded to the
      questionnaire. Results were analysed by percentage, and chi2 analysis was used
      where appropriate. The time for availability of images to requesting clinicians
      was 70% less for digital images compared to conventional radiography. The overall
      satisfaction between digital and conventional radiography was very similar, but
      most clinicians expressed an opinion that digital radiography offered significant
      image modification advantages.

PMID- 12060156
TI  - Colour duplex Doppler ultrasonography evaluation of non-vasculogenic male
      erectile dysfunction: An Indian perspective.
AB  - We present the study of colour duplex Doppler ultrasonography on Indian patients
      with non-vasculogenic erectile dysfunction. Patients with a history suggestive of
      psychogenic impotence along with a normal clinical response to intracavernosal
      papaverine were presumed to have non-vasculogenic erectile dysfunction. In our
      patients, the incidence of psychogenic impotence was much higher and the mean age
      of patients presenting with erectile dysfunction was lower as compared to
      patients from developed countries reported in research. The Doppler flowmetry
      showed much higher mean peak systolic velocities (PSVs) with a negative
      correlation between age and PSV. End diastolic velocity, resistive index and
      acceleration time values conformed to the literature.

PMID- 12060157
TI  - Parotid lymph-node metastases from cutaneous squamous-cell carcinomas: treatment
      outcome and prognostic factors following surgery and adjuvant radiotherapy.
AB  - Australia has the highest incidence of cutaneous squamous cell carcinoma (SCC) in
      the world. The majority of lesions occur in the head and neck, and regional lymph
      node metastases from cutaneous SCCs, though uncommon, reflect an aggressive
      manifestation. Surgery and adjuvant radiotherapy are currently considered best
      practice. Fifty-two eligible patients during 1980-1997 were identified in a
      retrospective review of patients treated within the department of Radiation
      Oncology, Westmead Hospital, Sydney. Relevant data were extracted from the files,
      referring clinicians and the New South Wales Cancer Council. The median age at
      diagnosis was 63 years and the majority were men (87%). Unfavourable pathological
      features were present in many of the patients. Only extranodal spread (P = 0.02)
      was identified as an independent predictor for locoregional recurrence on
      multivariate analysis. The cumulative locoregional recurrence rates were 28 and
      45% at 2 and 5 years, respectively. The 5-year cause-specific survival rate in
      this study was 65%. We conclude that parotid lymph-node metastases from cutaneous
      SCCs of the head and neck are associated with a high rate of locoregional
      recurrence and cause-specific mortality despite surgery and adjuvant
      radiotherapy. The role of altered fractionation after surgery as a means to
      further enhance locoregional control warrants further investigation.

PMID- 12060158
TI  - Epidural extramedullary haemopoiesis in thalassaemia.
AB  - Intrathoracic extramedullary haematopoiesis is a rare condition. Involvement of
      the spinal epidural space with haematopoietic tissue is rather unusual. A 31-year
      old-man with a known diagnosis of beta-thalassaemia was referred with focal back
      pain. Magnetic resonance imaging revealed diffuse bone-marrow changes, thoracic
      paraspinal masses and lobulated epidural masses, suggesting extramedullary
      haemopoiesis. The patient was treated with radiotherapy and blood transfusions.
      Follow-up MRI was performed for evaluation efficacy of the treatment.

PMID- 12060159
TI  - Preoperative diagnosis of bilateral tuberculous epididymo-orchitis following
      intravesical Bacillus Calmette-Guerin therapy for superficial bladder carcinoma.
AB  - We report a case of bilateral tuberculous epididymo-orchitis following
      intravesical Bacillus Calmette-Guerin (BCG) therapy for superficial bladder
      carcinoma in which the diagnosis was made by ultrasonography prior to surgery.
      The US findings include heterogeneous enlargement of the epididymis and testis,
      associated with scrotal-skin thickening and scrotal sinus track. Patients with
      bladder carcinoma treated with intravesical BCG therapy, the presence of scrotal
      swelling with scrotal-skin thickening and epididymal involvement suggests
      tuberculous epididymo-orchitis rather than testicular tumour. It is important to
      be aware of this rare complication and to be familiar with the ultrasonographic
      features so that appropriate treatment can be given.

PMID- 12060160
TI  - Acute tuberculous abscess of the thyroid gland.
AB  - Isolated tuberculous thyroid abscess is an extremely rare form of infection of
      the thyroid gland. We present a case of a female patient who presented with an
      acute abscess of thyroid gland associated with pain and fever and without
      cervical lymphadenopathy. We describe the pathology of the disease and the
      imaging findings with their differential diagnosis.

PMID- 12060161
TI  - Three-dimensional gadolinium-enhanced magnetic resonance angiography of pulmonary
      arteriovenous malformation.
AB  - Pulmonary arteriovenous malformations (AVMs) are rare vascular malformations of
      the lung. Although most patients are asymptomatic, AVMs can bleed and result in
      haemoptysis and haemothorax. We describes a case of pulmonary AVMs in a patient
      with Osler-Weber-Rendu syndrome with 3-D contrast-enhanced MR angiography.
      Magnetic resonance angiography provided accurately and non-invasively the number
      and size of the feeding arteries and draining veins.

PMID- 12060162
TI  - Cardiac hydatid disease: report of two cases.
AB  - Cardiac involvement in hydatid disease is rare, occurring in less than 2% of
      cases of hydatid infection. It can occur as part of a widespread systemic
      infection or as an isolated event. It may be asymptomatic for a long period
      before presenting with a myriad of non-specific symptoms. Imaging plays an
      important role in the diagnosis, surgical planning and follow up of cases.
      Current treatment involves attempted surgical resection (cystopericystectomy)
      with long-term follow-up chemotherapy (Albendazole). Both the disease and its
      surgical treatment carry a high complication rate, including rupture leading to
      anaphylaxis and death.

PMID- 12060163
TI  - Unusual clinical manifestations of the Nutcracker Syndrome.
AB  - The Nutcracker Syndrome, caused by compression of the left renal vein as it
      passes in a tight angle between the aorta and the superior mesenteric artery,
      usually presents with unexplained haematuria localized to the left ureteric
      orifice. We report on a series of cases where compression of the left renal vein
      caused prominent left-gonadal-vein reflux, which in turn resulted in lower-limb
      varices and varicocele formation.

PMID- 12060164
TI  - Lumbar artery pseudoaneurysm following renal biopsy: treatment with ultrasound
      guided thrombin injection.
AB  - latrogenic pseudoaneurysms are usually seen following arterial catheterization.
      However, we describe a case of a 23-year-old woman who developed a pseudoaneurysm
      of a lumbar artery following renal biopsy. In view of her progressing renal
      failure, arterial embolization was felt to be inappropriate, and although the
      pseudoaneurysm could be seen ultrasonically, guided compression could not be
      applied because of the location of the aneurysm deep to the lumbar musculature.
      Hence, the pseudoaneurysm was thrombosed by percutaneous ultrasound-guided
      injection of thrombin directly into the pseudoaneurysm sac. This resulted in
      immediate thrombosis of the aneurysm and no recurrence on follow-up imaging.
      Thrombin injection for femoral artery pseudoaneurysms following catheterization
      is becoming more widely accepted, and our case demonstrates that this technique
      might be applied to pseudoaneurysms elsewhere in the body.

PMID- 12060165
TI  - Extramammary Paget's disease: role of radiation therapy.
AB  - Extramammary Paget's disease (EMPD) is an uncommon premalignant skin condition
      that has been traditionally managed with surgery. A report of long-standing
      Paget's disease with transformation to invasive adenocarcinoma definitively
      managed with radiation therapy is presented. A review of cases of extramammary
      Paget's disease treated with radiation therapy is discussed. The use of radiation
      therapy should be considered in selected cases, as these studies demonstrate
      acceptable rates of local control when used as an adjunct to surgery, or as a
      definitive treatment modality.

PMID- 12060169
TI  - Afternoon listener.

PMID- 12060166
TI  - A safe percutaneous method to recanalize sharp venous occlusions that resist the
      passage of guidewires.
AB  - It is occasionally necessary to cross a sharp venous occlusion (a thin web of
      tissue without a lumen) and sometimes it is not possible to cross the stricture
      with a wire, so puncturing it with a sheathed needle is then required to enable
      stenting. Other methods have been reviewed; however, we think this balloon
      technique makes it a safer procedure.

PMID- 12060170
TI  - RE: RANZCR conference registration fees.

PMID- 12060177
TI  - The asylum debacle in Australia: a challenge for psychiatry.
AB  - OBJECTIVE: To examine the mental health consequences of contemporary Australian
      policies pertaining to asylum seekers and to consider the possible roles of
      psychiatrists in responding to this issue. METHODS: Historical and political
      factors driving policy are considered. The results of Australian studies
      examining the mental health of asylum seekers are reviewed. RESULTS: Available
      research shows high rates of trauma, posttraumatic stress disorder (PTSD) and
      depression in asylum seekers. The conditions of the postmigration environment
      influence outcomes. Psychiatrists working with other agencies continue to
      advocate for this group. Important roles include the provision of clinical
      services, undertaking and disseminating research, acting as expert witnesses and
      consultants, and writing reports for refugee applicants. CONCLUSIONS: Complex
      political motivations steer asylum policy. Psychiatric formulations are important
      in considering the impact of contemporary policy, but a wider ecological model is
      needed to understand acts of desperation displayed by asylum seekers,particularly
      those in long-term detention. Sustained effort will be needed to alter a policy
      of exclusion that has become entrenched.

PMID- 12060178
TI  - Research methods in psychiatric epidemiology: an overview.
AB  - OBJECTIVE: To provide an introduction to the concepts and methods of psychiatric
      epidemiology for non-specialist readers. METHODS: An overview of concepts and
      research procedures based on the published literature. CONCLUSION: Psychiatric
      epidemiology is a key mental health discipline that has adopted and developed a
      variety of methods and procedures for the study of complex mental disorders. In
      its future development, psychiatric epidemiology is likely to seek an integration
      of the conceptual and methodological advances of molecular biology and
      neuroscience within the population-based and social framework of epidemiology as
      a basic science of public health.

PMID- 12060179
TI  - The development, evolution and philosophy of a clinical research unit.
AB  - OBJECTIVE: To describe the development,evolution and philosophy of a clinical
      research unit. METHOD: The 20-year history of clinical psychiatric research in
      Christchurch is described. The variety of influences which have impacted upon the
      studies undertaken is acknowledged,as are the personal histories of key staff.
      CONCLUSIONS: Clinical research is potentially endangered. The maintenance and
      development of clinical research requires a mix of individual inquisitiveness and
      determination,local opportunity and political will. Despite a political desire
      for evidence-based medicine; most political policies and practices impede the
      development of new knowledge and the collection of new evidence.

PMID- 12060180
TI  - Research priorities in mental health, part 1: an evaluation of the current
      research effort against the criteria of disease burden and health system costs.
AB  - OBJECTIVE: To examine the amount of research that various mental disorders are
      currently receiving in Australia and compare this with the disease burden and
      health system costs attributable to these disorders. METHOD: A content analysis
      was carried out on a year's worth of published articles and a year's worth of
      competitive research grants. Abstracts of articles and grants were coded for a
      number of attributes, including the type of mental disorder covered. The
      percentage of articles and grant funding for various mental disorders was
      compared against published data on the disease burden and health system costs
      attributable to these disorders. RESULTS: Mental disorders contribute 19.1% of
      disease burden and 9.8% of health system costs, but receive only 8.9% of National
      Health and Medical Research Council funding. An examination of the distribution
      of research within the mental health area showed that substance use disorders are
      by far the most researched in terms of both publications and grant funding,
      followed by affective disorders. By contrast, affective disorders account for the
      most burden, followed by dementia, substance use and anxiety disorders. The
      biggest consumers of health system costs are dementia, affective disorders, and
      schizophrenia and other psychoses. CONCLUSIONS: While all mental disorders merit
      more research attention than they are currently receiving, affective disorders
      and dementia appear to be particularly under-researched given their contribution
      to disease burden and health system costs.

PMID- 12060181
TI  - Research priorities in mental health, Part 2: an evaluationof the current
      research effort against stakeholders' priorities.
AB  - OBJECTIVE: To examine the current distribution of mental health research in
      Australia and compare this with the priorities of various stakeholder groups.
      METHOD: A content analysis was carried out on a year's worth of published
      articles and a year's worth of competitive research grants. A questionnaire for
      stakeholders was developed in which respondents were asked to rate priorities for
      research using the same categories. Questionnaires were sent to mental health
      researchers,members of panels that evaluate mental health research grant
      applications,general practitioners, psychiatrists, clinical psychologists, mental
      health nurses, mental health consumer and carer advocates, and members of the
      National Mental Health Working Group. RESULTS: Different groups of stakeholders
      tended to have differing perspectives on research priorities, with some major
      differences between committees that evaluate research grants and consumer and
      carer groups. Different stakeholder groups also tended to obtain their
      information about research from different sources. However, there were also a
      number of areas of agreement. When different research topics are considered,the
      following tended to be under-researched: affective disorders,suicide, primary
      care and community settings, prevention and promotion,evaluation of services,
      Aboriginal and Torres Strait Islander peoples,and socially and economically
      disadvantaged people. CONCLUSIONS: It is of concern that committees that evaluate
      research are guided by different values from consumers and carers in setting
      priorities. Nevertheless, there is consensus across stakeholder groups that a
      number of areas should be a high priority.

PMID- 12060182
TI  - Depressive, positive, negative and parkinsonian symptomsin schizophrenia.
AB  - OBJECTIVE: Depressive symptoms are common in schizophrenia but their relationship
      to the positive and negative symptoms of the disorder and to extrapyramidal side
      effects remains unclear. Considerable overlap exists between these symptom
      clusters when rated with traditional clinical rating scales. The aim of this
      study was to investigate the relationship of depressive to positive, negative and
      parkinsonian symptoms using the recent adaptation of the Positive and Negative
      Syndrome Scale (PANSS). METHOD: The study involved the cross-sectional
      measurement of symptoms in a sample of community-treated and hospitalized
      patients with schizophrenia. Structured assessment included thePANSS, Montgomery
      Asberg Depression Rating Scale (MADRS) and the Extrapyramidal Side Effects Rating
      Scale (ESRS). RESULTS: Depressive symptoms were common and correlated with
      positive and negative symptoms. These correlations were of a similar magnitude
      using either the original PANSS factor structure or the newer pentagonal model.
      The overlap between depressive and negative symptoms was limited to certain items
      in the rating scales and there was a clear separation between these symptom
      clusters and the other items. Parkinsonian symptoms also correlated with negative
      symptoms rated with either PANSS model. CONCLUSION: Use of the pentagonal PANSS
      model does not improve its capacity to distinguish between depressive and
      negative symptoms. Positive, negative, parkinsonian and depressive symptoms
      overlap using common rating scales but there appears to be some separation
      between these symptom domains when rated with individual scale items rather than
      total scale scores.

PMID- 12060183
TI  - Thalamic and caudate volumes in monozygotic twins discordantfor schizophrenia.
AB  - OBJECTIVE: The thalamus and caudate nucleus are key subcortical structures in the
      fronto-striato-thalamic pathways that have been implicated in the pathogenesis of
      schizophrenia. Previous studies have been inconsistent in identifying structural
      and functional abnormalities in these structures. However, methodologies in these
      studies have been unreliable and some have not adequately matched patients and
      controls. METHODS: Using algebraically-manipulated double-echomagnetic resonance
      (MR) images, we developed a reliable method to estimate caudate and thalamic
      volumes in a group of 13 monozygotic(MZ) twins; eight discordant for
      schizophrenia and five normal.Initially, volumes were measured on four image
      types: proton density(PD), T2-weighted, summed (PD + T2) and subtracted (PD-T2)
      to determine the most reliable method. RESULTS: There was a significant method by
      region interaction, where caudate volumes measured on PD images were
      significantly larger than those measured on T2-weighted images, while the
      opposite was found for thalamic volumes. However, there was no interaction of
      method by diagnosis. Test-retest reliability was highest for the summed images.
      Using summed images to measure the volumes of the caudate and thalamus in each
      twin, we found significantly increased caudate volumes in affected twins compared
      to their unaffected cotwins,but no significant difference in thalamic volume.
      CONCLUSIONS: Our results in a small sample of MZ twins discordant for
      schizophrenia do not support the presence of structural abnormalities in the
      thalamus. The findings in the caudate are consistent with previously reported
      effects of antipsychotic medication. We also report a reliable method for
      assessing the volumes of subcortical structures. However, volumetric estimates of
      brain structures may be dependent on which method is used and the structure being
      assessed. Such interactions need to be considered in future studies investigating
      brain structural abnormalities in schizophrenia and other disorders.

PMID- 12060184
TI  - Implications of lipid biology for the pathogenesis of schizophrenia.
AB  - OBJECTIVE: Preclinical and clinical data suggest that lipid biology is integral
      to brain development and neurodegeneration. Both aspects are proposed as being
      important in the pathogenesis of schizophrenia. The purpose of this paper is to
      examine the implications of lipid biology, in particular the role of essential
      fatty acids (EFA), for schizophrenia. METHODS: Medline databases were searched
      from 1966 to 2001 followed by the cross-checking of references. RESULTS: Most
      studies investigating lipids in schizophrenia described reduced EFA, altered
      glycerophospholipids and an increased activity of a calcium-independent
      phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in
      vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated
      lower phosphomonoesters (implying reduced membrane precursors) in first- and
      multi-episode patients. In contrast, phosphodiesters were elevated mainly in
      first-episode patients (implying increased membrane breakdown products), whereas
      inconclusive results were found in chronic patients. EFA supplementation trials
      in chronic patient populations with residual symptoms have demonstrated
      conflicting results. More consistent results were observed in the early and
      symptomatic stages of illness, especially if EFA with a high proportion of
      eicosapentaenoic acid was used. CONCLUSION: Peripheral blood cell, brain necropsy
      and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized
      membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane
      turnover at illness onset and persisting membrane abnormalities in established
      schizophrenia. Cellular processes regulating membrane lipid metabolism are
      potential new targets for antipsychotic drugs and might explain the mechanism of
      action of treatments such as eicosapentaenoic acid.

PMID- 12060185
TI  - The experiences of people with schizophrenia living in supported accommodation: a
      qualitative study using grounded theory methodology.
AB  - OBJECTIVE: This study aims to develop a detailed analysis of the subjective
      experiences of people with schizophrenia living in highly staffed supported
      accommodation. METHODS: Thirteen participants were audiotaped for one
      semistructured interview. The transcription and identified themes were discussed
      with the participants for feedback. Analysis of the interviews and feedback used
      grounded theory methodology. RESULTS: A unifying social theory was developed
      called 'A Way to Survive'. Survival experiences for these participants ranged
      from the life threatening to the mundane. The major categories linked to survival
      were; psychosis, identity, alienation, God/religion, family, basic life stuff and
      health services. CONCLUSIONS: A number of implications for service development
      and clinical practice were identified. Qualitative methodology for people with
      persistent psychotic symptoms allows for a depth and richness of information that
      may not be accessed using quantitative techniques. A number of difficulties in
      both collection and analysis arise from the presence of psychosis and further
      research in this area is required.

PMID- 12060186
TI  - No significant association between prenatal exposure poliovirus epidemics and
      psychosis.
AB  - OBJECTIVE: To examine the association between prenatal exposure to poliovirus
      infection and later development of schizophrenia or affective psychosis in a
      Southern Hemisphere psychiatric register. METHODS: We calculated rates of
      poliomyelitis cases per 10 000 background population and rates for
      schizophrenia(n = 6078) and affective psychosis (n = 3707)per 10 000 births for
      the period 1930-1964. Empirically weighted regression was used to measure the
      association between a given psychosis birth-rate and a poliomyelitis epidemic
      during gestation. RESULTS: There was no statistically significant association
      between exposure to a poliomyelitis epidemic during gestation and subsequent
      development of schizophrenia or affective psychosis. CONCLUSIONS: The lack of a
      consistent statistically significant association between poliovirus epidemics and
      schizophrenia suggests that either poliovirus may have a small effect which is
      only detectable with large data-sets and/or the effect may be modified by
      location. Further investigation of such inconsistencies may help elucidate
      candidate risk-modifying factors for schizophrenia.

PMID- 12060187
TI  - Melancholia: definitions, risk factors, personality, neuroendocrine markers and
      differential antidepressant response.
AB  - OBJECTIVE: To evaluate the CORE measure of melancholia, against the DSM-IV
      construct of melancholia. To evaluate the validity of both the CORE and DSM-IV
      constructs of melancholia against psychosocial risk factors, anxiety and
      personality disorder comorbidity, neuroendocrine markers and differential anti
      depressant response to fluoxetine and nortriptyline. METHOD: One hundred and
      ninety-five outpatients with major depression were evaluated for melancholia with
      both the DSM-IV criteria and the CORE evaluation. Both constructs were evaluated
      for validity against psychosocial risk factors, comorbidity, biological markers
      and differential antidepressant response. RESULTS: The CORE measure has
      satisfactory interrater reliability when used dimensionally, but has unacceptably
      low agreement for making a categorical diagnosis of melancholia. There is
      remarkably poor agreement (kappa = 0.11) between the CORE and DSM-IV criteria for
      melancholia. Neither the DSM-IV nor CORE criteria for melancholia identified
      subgroups of patients with better childhood environments or less anxiety or
      personality disorder comorbidity. The CORE criteria for melancholia, but not DSM
      IV, identified patients with neuroendocrine disturbance. CORE scores also were
      associated with differential responses to fluoxetine and nortriptyline, but not
      in anticipated directions. Thus, high CORE scores were associated with a higher
      recovery rate with fluoxetine than nortriptyline. CONCLUSION: While the episode
      specifier of melancholia should be retained in diagnostic systems, the DSM-IV
      criteria were not validated against any of the variables examined in this study.
      The CORE construct of melancholia, was validated against neuroendocrine measures,
      and was associated with a differential antidepressant response. However, the
      limits imposed by interrater reliability,suggest the CORE measure should be used
      dimensionally and not to make a categorical diagnosis of melancholia.

PMID- 12060188
TI  - Patterns and predictors of remission, response and recovery in major depression
      treated with fluoxetine or nortriptyline.
AB  - OBJECTIVE: The first objective of this paper was to describe the pattern of
      remission, response and recovery in patients with major depression who were
      randomised for treatment with fluoxetine ornortriptyline. The second objective
      was to report on the demographic and diagnostic predictors of the response and
      recovery in these depressed patients. METHOD: One hundred and ninety-five
      patients with major depression were recruited for this outpatient study. After a
      detailed clinical and neurobiological evaluation patients were randomized to
      receive either fluoxetine or nortiptyline as an initial antidepressant treatment.
      RESULTS: Of the 195 depressed patients randomised to treatment,154 completed an
      adequate 6-week trial of either fluoxetine or nortriptyline as their initial
      antidepressant. Of the 41 patients who did not complete an adequate trial the
      dropout rate was higher on those randomized to nortriptyline (p = 0.02). There
      was also an important interaction of drug and gender in determining dropouts in
      that women did not complete an adequate trial with nortriptyline and men did not
      complete an adequate trial with fluoxetine (p = 0.002). Of the 154 patients who
      completed an adequate 6-week antidepressant trial there were no significant
      differences in 6-week measures of depression severity or of percentage
      improvement. However, if we use an intention to treat analysis and dichotomise
      outcomes into response,remission or recovery; then recovery rates were
      significantly higher with fluoxetine than nortriptyline (p = 0.005). Using an
      intention to treat analysis fluoxetine was superior tonortriptyline in women, in
      those less than 25-years old, and in those with atypical depression. Independent
      of drug, those with chronic depressions had a poorer outcome. CONCLUSION: In this
      sample of depressed patients randomized tonortriptyline or fluoxetine the change
      in depressive symptoms over 6 weeks were comparable between fluoxetine and
      nortriptyline. However,when we look at the more clinically important variable of
      recovery then fluoxetine was superior to nortriptyline. Predictors of a poorer
      response to nortriptyline were gender, young age and atypical depression. The
      results challenge traditional beliefs that selective serotonin re-uptake
      inhibitors (SSRIs) and tricyclic antidepressant have comparable efficacy.

PMID- 12060190
TI  - A study of the use of seclusion in an acute psychiatric service.
AB  - OBJECTIVE: In recent years, increased attention has been paid to significantly
      restrictive practices taking place in psychiatric services in New Zealand. The
      aim of this study was to prospectively examine the frequency of use of seclusion
      and the factors associated with its use in the acute general adult psychiatric
      wards serving the Waikato area. METHODS: Information on the use of seclusion and
      relevant demographic data were collected over a 9-month period in 2000. The
      patterns of locked seclusion use and the characteristics of patients who had been
      secluded were examined. Analysis compared patients requiring one or more episode
      of seclusion (n = 84) with those never secluded (n = 455). RESULTS: Of a total of
      539 patients admitted to the general adult unit during our study period, 84 (16%)
      were secluded in 129 seclusion episodes. About two-thirds of the seclusion events
      were initiated in the first week of the patient's admission, and three-quarters
      of secluded patients had only one episode. The median duration of seclusion was
      14 hours. Comparison of gender and race revealed significant differences between
      the groups. Diagnosis, but not age, had a significant effect on whether a patient
      would be secluded. Seclusion was mainly associated with risk of, or actual,
      violence toward staff, patients or property. CONCLUSIONS: This study shows that
      seclusion is regularly practiced in the psychiatric wards of the Waikato area. In
      the majority of cases, its use was related to actual or threatened violence.
      Male, non-European patients and patients with certain diagnoses were at
      particular risk for seclusion. More research is required to examine the most
      effective use of seclusion and also the development and use of alternative
      strategies in controlling aggressive behaviour.

PMID- 12060189
TI  - A comparison of patient clinical and social outcomes before and after the
      introduction of an extended-hours community mental health team.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of the addition
      of standard community treatment to a hospital-based service in a regional
      district of Australia. METHOD: The study was a naturalistic investigation of a
      routine clinical service and utilized a longitudinal panel design. Two matched
      groups of seriously mentally ill patients were recruited,one before the addition
      of the community mental health team (CMHT)and one after. Each sample was followed
      up for one year using a semistructured questionnaire and instruments including
      the Brief Psychiatric Rating Scale, the Global Assessment Scale, the Life Skills
      Profile and the Rosenberg Self-Esteem Scale as well as hospital records. RESULTS:
      Patients in both groups showed similar patterns of improvements. Although the
      aims of the new service included reducing in-patient utilization and improving
      social functioning,there were few significant differences between the two groups.
      While the number of admissions and length of stay were lower in the post
      CMHTsample most were admitted rather than treated in their homes by the CMHT.
      CONCLUSION: The study concludes that better outcomes might have been achieved if
      the aims of the CMHT had been limited to either crisis or rehabilitation
      interventions, but not both. More attention needs to be paid to the service
      context in which model programmes are introduced so that new developments can be
      more closely tailored to the realities of what is likely to be achievable.

PMID- 12060191
TI  - A study of factors affecting suicide in Aboriginal and 'other' populationsin the
      Top End of the Northern Territory through an audit of coronial records.
AB  - OBJECTIVE: A recent increase in suicide among the Tiwi people of Bathurst and
      Melville Islands in the Northern Territory led to a review of recent suicides in
      the Top End of the Northern Territory using the coroner's records. The aim of the
      review was to establish through the coronial files whether there were any
      significant differences in the factors that related to suicide in Aboriginal
      people and other people in the Top End. METHOD: Coronial determinations of
      suicide in the Top End for the years 1991-1998 were examined using a structured
      coding instrument. RESULTS: Hanging was a prominent method of suicide among
      Aboriginal people. Aboriginals who committed suicide were more likely to have a
      history of self-harm behaviour. Suicide among Aboriginal people was irregular in
      distribution with a higher general risk for Aboriginal people resident in the
      east Arnhem region. A recent rise in suicide in the Tiwi community occurred
      against a background of social disruption similar to that which occurred against
      suicides in the Aboriginal population of the Kimberley region in Western
      Australia. CONCLUSIONS: There are some important differences in the factors
      attributed to suicide in the Aboriginal and other populations in the Top End.
      Furthermore, our study highlights regional differences in suicide risk among
      different Aboriginal populations in the Top End.

PMID- 12060192
TI  - Pathological gambling and comorbid substance use.
AB  - OBJECTIVE: The objective of this study was to determine the rates of substance
      use problems in a sample of diagnosed pathological gamblers seeking treatment in
      a university teaching hospital cognitive behavioural outpatient clinic. METHODS:
      A semistructured interview schedule and the composite international diagnostic
      interview (CIDI-auto) were administered to assess substance dependence in a
      sample of 75 poker-machine gamblers meeting DSM-IV and South Oaks gambling screen
      (SOGS) criteria for pathological gambling. Both the self-reported rates and the
      proportion meeting criteria for a psychiatric disorder were determined. RESULTS:
      The rates for substance use disorder within a sample of treatment-seeking
      pathological gamblers is higher as compared to general population figures. Gender
      differences were found with more current alcohol-abuse problems reported among
      male than female participants. Non-alcohol-related substance abuse was relatively
      lower than rates reported by other studies in the literature. CONCLUSIONS:
      Substance abuse is a common comorbid condition of pathological gambling and
      therefore should be screened for in routine clinical assessments. Failure to
      identify and treat comorbid substance-use disorders in gamblers may lead to
      higher relapse rates.

PMID- 12060193
TI  - Shrinking away from psychiatry? A survey of Australian medical students' interest
      in psychiatry.
AB  - OBJECTIVE: We sought to examine the attitudes of newly recruited medical students
      towards psychiatry and other specialties to determine what factors influence
      their career choice options. METHOD: We surveyed the attitudes of 655 medical
      students using a 31-item self-report questionnaire. RESULTS: Australian medical
      students rated the ability to help patients as the most important aspect of a
      specialty in determining their choice. Attraction to psychiatry was based on the
      specialty being interesting and intellectually challenging,and providing a career
      that promised job satisfaction with good prospects and enjoyable work. Females
      expressed a greater interest in psychiatry and were more likely to consider
      pursuing it as a career, principally due to a greater interest in the subject
      matter and a stronger desire for interaction with patients. The least attractive
      aspects of psychiatry were its lack of prestige among the medical community and a
      perceived absence of a scientific foundation. CONCLUSION: The attitudes of
      medical students can perhaps be modified and recruitment into psychiatry enhanced
      by presenting the reality of psychiatry today - namely the wide range of
      available therapeutic processes, the predominantly positive outcomes, the
      interesting and intellectually challenging nature of the subject and its
      nurturing and accommodating work environment.

PMID- 12060194
TI  - The impact of mainstreaming on patient care in Australian emergency departments
      and liaison services.

PMID- 12060195
TI  - Citalopram-Clonazepam combination for primary depersonalization disorder: a case
      report.

PMID- 12060196
TI  - Zolpidem, vascular headache, and hallucinations in an adolescent.

PMID- 12060197
TI  - Lithium induced raised intracranial pressure.

PMID- 12060198
TI  - Is it ethical to ignore significant mental health problems?

PMID- 12060199
TI  - Do the newer antidepressant have mood stabilizing properties?

PMID- 12060200
TI  - Uses of olanzapine.

PMID- 12060222
TI  - Photosynthesis nuclear genes generally lack TATA-boxes: a tobacco photosystem I
      gene responds to light through an initiator.
AB  - The promoter architecture of the nuclear-encoded photosystem I genes was studied
      using a tobacco gene, psaDb, as a model case. Linker scanning mutations revealed
      that the psaDb promoter does not have a TATA box. Instead, pyrimidine-rich
      Initiator (Inr) elements that overlap the transcription start sites are essential
      for light-responsive transcription of this gene. When the psaDb promoter was
      mutated to have a TATA-box but no Inr, light-responsive transcription was
      impaired, indicating that the regulatory system of this gene prefers Inr to a
      TATA box. As very little is known about plant TATA-less promoters, we
      subsequently examined whether this promoter architecture is unique to psaDb.
      Computer analysis of 232 plant promoters revealed surprising features; the
      majority of photosynthesis nuclear genes lacked TATA boxes, although the
      frequency of the TATA-less promoters in non-photosynthesis genes was less than
      10%. These results strongly suggest that TATA-independent transcription
      mechanisms play important roles in the regulated expression of photosynthesis
      nuclear genes.

PMID- 12060223
TI  - Characterization of Arabidopsis enhanced disease susceptibility mutants that are
      affected in systemically induced resistance.
AB  - In Arabidopsis, the rhizobacterial strain Pseudomonas fluorescens WCS417r
      triggers jasmonate (JA)- and ethylene (ET)-dependent induced systemic resistance
      (ISR) that is effective against different pathogens. Arabidopsis genotypes unable
      to express rhizobacteria-mediated ISR against the bacterial pathogen Pseudomonas
      syringae pv. tomato DC3000 (Pst DC3000) exhibit enhanced disease susceptibility
      towards this pathogen. To identify novel components controlling induced
      resistance, we tested 11 Arabidopsis mutants with enhanced disease susceptibility
      (eds) to pathogenic P. syringae bacteria for WCS417r-mediated ISR and pathogen
      induced systemic acquired resistance (SAR). Mutants eds4-1, eds8-1 and eds10-1
      failed to develop WCS417r-mediated ISR, while mutants eds5-1 and eds12-1 failed
      to express pathogen-induced SAR. Whereas eds5-1 is known to be blocked in
      salicylic acid (SA) biosynthesis, analysis of eds12-1 revealed that its impaired
      SAR response is caused by reduced sensitivity to this molecule. Analysis of the
      ISR-impaired eds mutants revealed that they are non-responsive to induction of
      resistance by methyl jasmonate (MeJA) (eds4-1, eds8-1 and eds10-1), or the ET
      precursor 1-aminocyclopropane-1-carboxylate (ACC) (eds4-1 and eds10-1). Moreover,
      eds4-1 and eds8-1 showed reduced expression of the plant defensin gene PDF1.2
      after MeJA and ACC treatment, which was associated with reduced sensitivity to
      either ET (eds4-1) or MeJA (eds8-1). Although blocked in WCS417r-, MeJA- and ACC
      induced ISR, eds10-1 behaved normally for several other responses to MeJA or ACC.
      The results indicate that EDS12 is required for SAR and acts downstream of SA,
      whereas EDS4, EDS8 and EDS10 are required for ISR acting either in JA signalling
      (EDS8), ET signalling (EDS4), or downstream JA and ET signalling (EDS10) in the
      ISR pathway.

PMID- 12060224
TI  - Constitutive expression of ETHYLENE-RESPONSE-FACTOR1 in Arabidopsis confers
      resistance to several necrotrophic fungi.
AB  - Infection of a plant by a pathogen induces a variety of defense responses that
      imply the action of several signaling molecules, including salicylic acid (SA),
      jasmonic acid (JA) and ethylene (E). Here we describe the role of ETHYLENE
      RESPONSE-FACTOR1 (ERF1) as a regulator of ethylene responses after pathogen
      attack in Arabidopsis. The ERF1 transcript is induced on infection by Botrytis
      cinerea, and overexpression of ERF1 in Arabidopsis is sufficient to confer
      resistance to necrotrophic fungi such as B. cinerea and Plectosphaerella
      cucumerina. A positive co-operation between E and SA pathways was observed in the
      plant response to P. cucumerina. Infection by Pseudomonas syringae tomato DC3000,
      however, does not affect ERF1 expression, and activation of ethylene responses by
      ERF1 overexpression in Arabidopsis plants reduces tolerance against this
      pathogen, suggesting negative crosstalk between E and SA signaling pathways, and
      demonstrating that positive and negative interactions between both pathways can
      be established depending on the type of pathogen.

PMID- 12060225
TI  - A long leader intron of the Ostub16 rice beta-tubulin gene is required for high
      level gene expression and can autonomously promote transcription both in vivo and
      in vitro.
AB  - A 2 kb DNA fragment, upstream of the rice beta-tubulin isotype 16 (Ostub16)
      coding sequence, was isolated using inverse PCR and screening of a tubulin
      enriched lambda library. An intron (863 bp) present in the 5' untranslated region
      (5' UTR) is spliced out to produce the most abundant mRNA species which
      corresponds to the previously cloned Ostub16 cDNA. Transient expression assays
      performed on rice embryogenic calluses with chimeric Ostub16::GUS constructs
      demonstrated that the entire 2 kb upstream sequence has a strong promoter
      activity, and that the 863 bp intron is required for high-level GUS expression.
      In addition, the intron sequence is capable per se of sustaining a weak but
      consistent GUS expression. Two rare Ostub16 transcripts, with a start site
      mapping within this intron sequence, were detected in rice coleoptile cells. The
      transcription start site mapped at position -290 with respect to the ATG codon,
      and the shorter molecule originated from splicing of the same precursor mRNA.
      Therefore transcriptional expression of rice beta-tubulin isotype 16 results in
      the synthesis of two premRNA molecules (I and II) encoding for three different
      mRNA species. We discuss these findings in terms of function and molecular
      evolution of the mechanisms that control plant beta-tubulin gene expression.

PMID- 12060226
TI  - E2F sites that can interact with E2F proteins cloned from rice are required for
      meristematic tissue-specific expression of rice and tobacco proliferating cell
      nuclear antigen promoters.
AB  - Plants have recently been found to have E2F-like and Rb-like proteins, regulators
      responsible for the G1(G0)-S phase transition of the cell cycle in animals. Here
      we show that E2F is involved in transcription of plant genes for proliferating
      cell nuclear antigen (PCNA), which is required for DNA replication. Potential E2F
      binding sites found in the rice PCNA promoters mediated transcriptional
      activation in actively dividing cells and tissues of tobacco, but not
      transcriptional repression in terminally differentiated tissues, as also observed
      for the PCF binding sites previously found in the rice promoter. Similar results
      were obtained from analyses for a PCNA promoter isolated from tobacco, which
      contained two E2F-like sites, each with a different degree of contribution to the
      promoter activation. These E2F-like sites except for a rice site were indeed
      bound specifically by recombinant proteins of rice E2F, OsE2F1 and OsE2F2, and
      complexes of OsE2F1 with Arabidopsis DP proteins. Furthermore, OsE2F1 had the
      ability to transactivate an E2F-reporter gene containing the tobacco E2F site on
      co-expression with an Arabidopsis DP, and the transactivation was greatly
      enhanced by tagging a canonical nuclear localization signal to OsE2F1, suggesting
      a nuclear import-mediated regulation of the OsE2F1 function. In addition, we
      found that a large number of replication- and mismatch repair-associated genes in
      Arabidopsis contain E2F binding sequences conserved in their predicted promoter
      regions.

PMID- 12060228
TI  - Tumorous shoot development (TSD) genes are required for co-ordinated plant shoot
      development.
AB  - This report describes the identification of novel plant genes that are required
      to ensure co-ordinated post-embryonic development. After germination the tumorous
      shoot development mutants of Arabidopsis thaliana develop disorganized tumorous
      tissue instead of organized leaves and stems. This results in green callus-like
      structures, which are capable of unlimited growth in vitro on hormone-free
      medium. The tsd mutants are recessive and belong to three complementation groups
      (tsd1, tsd2, tsd3). The genes were mapped to the bottom of chromosomes 5 and 1,
      and the top of chromosome 3, respectively. Histological analyses showed that the
      tsd mutants have different developmental defects. The shoot apical meristem of
      tsd1 formed only rudimentary leaves and was characterized by a degenerating L1
      cell layer. tsd2 mutants had reduced cell adhesion and altered cell division
      planes in the L2 and L3 cell layers. The tumorous tissue of tsd3 mutants
      originated from the base of the leaf. Cytokinin levels that are inhibitory to the
      growth of wild-type seedlings bring about an enhanced growth response in all the
      tsd mutants. The steady state transcript levels of the histidine kinase CKI1 gene
      and the KNAT1 and STM homeobox genes were increased in tsd mutants, while mRNA
      levels of cell cycle genes were not altered. We hypothesize that the TSD gene
      products negatively regulate cytokinin-dependent meristematic activity during
      vegetative development of Arabidopsis.

PMID- 12060227
TI  - Involvement of the Arabidopsis alpha-DOX1 fatty acid dioxygenase in protection
      against oxidative stress and cell death.
AB  - alpha-dioxygenases (alpha-DOXs) catalyze the primary oxygenation of fatty acids
      into a newly identified group of oxylipins. Here we show that expression of the
      Arabidopsis alpha-DOX1 gene is induced in response to both incompatible and
      compatible bacterial infections. However, the level of alpha-DOX1 mRNA and
      dioxygenase activity appears earlier and reaches higher values when infection
      promotes a hypersensitive reaction. Furthermore, whereas gene expression is
      confined to necrotic lesions during the hypersensitive response, it occurs
      throughout the chlorotic area during a compatible interaction. Accumulation of
      alpha-DOX1 transcripts is impaired in SA-compromised plants and induced by SA and
      by chemicals generating nitric oxide (NO), intracellular superoxide or singlet
      oxygen, three signals mediating host cell death. Transgenic plants with altered
      levels of alpha-dioxygenase react like wild-type plants to a compatible pathogen.
      In contrast, plants with reduced activity develop a more rapid and severe
      necrotic response than wild-type plants to incompatible bacteria and paraquat
      treatment, respectively, and a milder response when alpha-DOX1 is overproduced.
      Our results suggest that plant alpha-dioxygenases are used to generate lipid
      derived molecules for a process that protects plant tissues from oxidative stress
      and cell death.

PMID- 12060229
TI  - Herbivore-induced volatiles induce the emission of ethylene in neighboring lima
      bean plants.
AB  - Herbivore attacks induce leaves to emit a specific blend of volatiles. Here we
      show that exposure to Tetranychus urticae-induced volatiles, as well as T.
      urticae infestation and artificial wounding, activates the transcription of the
      genes involved in the biosynthesis of ethylene [S-adenosylmethionine (SAM)
      synthetase and 1-aminocyclopropane-1-carboxylic acid oxidase] and a gene involved
      in the biosynthesis of polyamines from SAM (SAM decarboxylase) in lima bean
      leaves. Moreover, exposure of leaves to any one of the seven major chemical
      components of T. urticae-induced volatiles also induces expression of these
      genes. Furthermore, we found that, when lima bean plants were exposed to T.
      urticae-induced volatiles, they emitted ethylene. Lima bean plants infested by T.
      urticae and artificially wounded plants also emitted ethylene. Endogenous
      polyamine levels were not increased in the exposed leaves or the infested leaves,
      suggesting that polyamine production from SAM was only slightly promoted at the
      metabolic levels present in the leaves. We found that jasmonate (JA) accumulated
      in leaves exposed to T. urticae-induced volatiles, and that both JA and
      salicylate (SA) accumulated in leaves infested by T. urticae. These findings, as
      well as results of pharmacological analyses, suggest that, in leaves exposed to
      T. urticae-induced volatiles, ethylene biosynthesis might be regulated by
      pathways involving JA and the ethylene positive feedback loop. They also suggest
      that ethylene biosynthesis might be regulated by signaling pathways involving JA,
      SA and ethylene in T. urticae-infested leaves.

PMID- 12060230
TI  - Golgi secretion is not required for marking the preprophase band site in cultured
      tobacco cells.
AB  - The preprophase band predicts the future cell division site. However, the
      mechanism of how a transient preprophase band fulfils this function is unknown.
      We have investigated the possibility that Golgi secretion might be involved in
      marking the preprophase band site. Observations on living BY-2 cells labeled for
      microtubules and Golgi stacks indicated an increased Golgi stack frequency at the
      preprophase band site. However, inhibition of Golgi secretion by brefeldin A
      during preprophase band formation did not prevent accurate phragmoplast fusion,
      and subsequent cell plate formation, at the preprophase band site. The results
      show that Golgi secretion does not mark the preprophase band site and thus does
      not play an active role in determination of the cell division site.

PMID- 12060231
TI  - Molecular analysis of the acetolactate synthase gene of Chlamydomonas reinhardtii
      and development of a genetically engineered gene as a dominant selectable marker
      for genetic transformation.
AB  - Genomic and cDNA clones of the acetolactate synthase (ALS) gene of Chlamydomonas
      reinhardtii have been isolated from a mutant, c85-20 (Hartnett et al., 1987),
      that is resistant to high concentrations of sulfometuron methyl (SMM) and related
      sulfonylurea herbicides. Comparison of the ALS gene sequences from the wild-type
      and the SMM resistant (SMMr) strains revealed two amino acid differences in the
      mature enzyme, a lysine to threonine change at position 257 (K257T) and a leucine
      to valine change at position 294 (L294V). Transformation of wild-type C.
      reinhardtii with the mutant ALS gene produced no transformants with ability to
      grow in the presence of a minimum toxic concentration of SMM (3 microm).
      Substitution of the ALS promoter with the promoter of the C. reinhardtii Rubisco
      small subunit gene (RbcS2) permitted recovery of SMMr colonies. In vitro
      mutagenesis of the wild-type ALS gene to produce various combinations of
      mutations (K257T, L294V and W580L) indicated that the K257T mutation was
      necessary and sufficient to confer the SMMr phenotype. Optimum transformation
      rates were obtained with two constructs (pJK7 and pRP-ALS) in which all introns
      in the coding region were present. Rates of transformation with construct pJK7
      were approximately 2.5 x 10-4 transformants/cell (i.e. one transformant for each
      of 4000 initial cells) using electroporation and 8.5 x 10-6 transformants/cell
      using the glass bead vortexing method. These results suggest that pJK7 and pRP
      ALS can serve as important additional dominant selectable markers for the genetic
      transformation of C. reinhardtii.

PMID- 12060233
TI  - Plant aquaporins.
AB  - Aquaporins are ubiquitous membrane channel proteins that facilitate and regulate
      the permeation of water across biological membranes. Aquaporins are members of
      the MIP family and some of them seem to be also able to transport other molecules
      such as urea or glycerol. In the plant kingdom, a single plant expresses a
      considerably large number of MIP homologues. These homologues can be subdivided
      into four groups (PIP, TIP, NIP, SIP) with highly conserved amino acid sequences
      and intron positions in each group. Since their discovery, advancing knowledge of
      their structure led to an understanding of the basic features of the water
      transport mechanism. An optimal water balance is essential to the homeostasis of
      most organisms, and aquaporins may be one of the mechanisms involved under
      changing environmental and developmental conditions. In fact, this may be one
      reason for the abundance and diversity of aquaporins, in particular in plants. In
      addition, exposure to different types of stress alters water relations and thus,
      aquaporins may be involved in stress responses as well. The transcriptional
      and/or post-translational regulation of aquaporins would determine changes in
      membrane water permeability. Both phosphorylation and translocation to/from
      vesicles have been reported as post-translational mechanisms. However,
      translocation in plants has not yet been shown. Although significant advances
      have been achieved, complete understanding of aquaporin function and regulation
      remains elusive.

PMID- 12060234
TI  - A CDPK type protein kinase is involved in rice SPS light modulation.
AB  - A protein kinase activity that can phosphorylate and inactivate rice (Oryza
      sativa) sucrose-phosphate synthase (SPS; UDP-glucose: d-fructose-6-phosphate-2
      glucosyl transferase, EC 2.4.1.14) was measured in extracts prepared from leaves
      exposed to light-dark transitions. Enzyme activity present in extracts from dark
      leaves was about 5-fold higher than the activity in extracts from leaves that had
      been collected in the light. The protein kinase (named R-SPSK) was purified about
      100-fold from dark leaves and its biochemical properties were studied. The
      micromolar dependence of Ca2+ exhibited by R-SPSK, and its response to calmodulin
      antagonists was similar to the properties associated with members of the plant
      Calcium-Dependent Protein Kinase (CDPK) family. Two modulators of SPS activity,
      Pi and Glc-6-P, were examined for an effect on R-SPSK. While Glc-6-P did not
      affect R-SPSK activity, Pi drastically increased the kinase activity. Taken
      together, these data provide evidence that SPS may be regulated by a CDPK type
      protein-kinase whose activity is modulated by light-dark transitions and
      stimulated by Pi, the negative effector of SPS activity.

PMID- 12060235
TI  - Diurnal variation of dimethylallyl diphosphate concentrations in oak (Quercus
      robur) leaves.
AB  - In the present work a rapid and sensitive non-radioactive assay for the
      determination of cellular dimethylallyl diphosphate (DMADP) was developed and
      used for the analysis of the diurnal variation of DMADP levels in oak leaves. The
      method is based on the acid-catalysed hydrolysis of DMADP to isoprene, which
      subsequently is determined by gas chromatography. Diurnal variation of cellular
      DMADP levels in oak leaves of young saplings was measured on 6 days in 1998 and
      1999, showing a 2 to 3-fold light-dependent increase from approximately 15 pmol
      mg-1 DW in the night to 31-75 pmol mg-1 DW around noon. The leaf DMADP contents
      showed a significant positive correlation with net assimilation and isoprene
      emission rates, indicating that the availability of cellular DMADP might be an
      important regulatory factor of leaf isoprene emission.

PMID- 12060236
TI  - Electrophysiological characterization of tomato hypocotyl putative action
      potentials induced by cotyledon heating.
AB  - Young tomato plants (Lycopersicon esculentum, 8 days old) were given a heat-wound
      to a cotyledon. The resulting electrical activity at the hypocotyl level was
      monitored with intracellular microelectrodes. We observed an original pattern of
      slow wave potentials (SWPs), consisting of 2-3 slow waves, with associated
      spikes. The electrophysiological study of the SWPs confirms previous conclusions
      that the SWPs are due to the inhibition of an active component of the membrane
      potential. The electrophysiological study of the spikes shows that they fit
      particularities of putative action potentials (APs). They seem to be triggered by
      the depolarization accompanying the SWPs and thus can appear late during the SWP.
      An ionic characterization of the spikes by using different extracellular ionic
      concentrations and channel blockers suggests that anionic channels might be
      involved, carrying SO42- ions. The channels activity might be down regulated by
      the calcium released by the vacuole during the SWPs and APs. A better
      characterization of the nature of these APs could permit the understanding of the
      information transmission mechanisms in higher plants.

PMID- 12060237
TI  - Salicylic acid modulates ozone-induced hypersensitive cell death in tobacco
      plants.
AB  - Ozone-tolerant Bel B and ozone-sensitive Bel W3 tobacco cultivars were subjected
      to acute ozone fumigation (200 p.p.b. for 3 h) and the subcellular localization
      of H2O2 was then studied. H2O2 accumulated on the cell walls and plasma membrane
      of both cultivars but the accumulation pattern differed greatly. H2O2 production
      was high in both cultivars immediately after fumigation, but, in the tolerant Bel
      B cultivar, after 7 h was only detected in some spongy cells adjacent to
      epidermal cells. Instead, in the sensitive Bel W3 cultivar, accumulation was
      still abundant in the cell walls of palisade, spongy and epidermal cells at this
      time. Significant changes in apoplastic ascorbate pool were noted in both
      cultivars in the first hours after fumigation. As the reduced ascorbate content
      remained unchanged, the marked increase in total ascorbate must have originated
      from the striking increase in dehydroascorbate, particularly in the ozone
      sensitive Bel W3. Exposure of plants to ozone resulted in a marked transient
      increase in both free and conjugated salicylic acid (SA) as well as an increase
      in the activity of benzoic acid 2-hydroxylase which catalyses SA biosynthesis. SA
      induction differed greatly in the two cultivars, in that: (1) SA accumulation was
      far greater in the ozone-sensitive Bel W3 cv. and (2) the maximum SA peak was
      delayed in Bel W3 and observed only 7 h after fumigation ended. These results
      suggest that a high SA content, as documented in the ozone-sensitive Bel W3
      cultivar, could trigger the production of ROS with subsequent SA-mediated cell
      death.

PMID- 12060238
TI  - Non-enzymatic protein modification by the Maillard reaction reduces the
      activities of scavenging enzymes in Vigna radiata.
AB  - The non-enzymatic modification of proteins through the Maillard reaction plays an
      important role in the loss of seed viability during seed storage. In the present
      study we examined whether the Maillard reaction reduces the activities of
      scavenging enzymes in Vigna radiata (mung bean) seeds during storage. Seeds were
      stored under various conditions for different duration. Maillard products were
      monitored by measuring protein fluorescence, and the activities of glutathione
      reductase (GR), superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase
      (CAT) and peroxidase (POX) were determined. The accumulation of Maillard products
      in seed axes increased during storage with increasing moisture content and
      temperature, and was correlated with the decline in seed vigour. The activities
      of GR, CAT and APX decreased in proportion to the increase in Maillard products
      at all the moisture contents and temperatures tested. These enzymatic changes
      were also correlated with seed vigour. However, the activities of SOD and POX
      remained unchanged and appeared to be less sensitive to the Maillard reaction.

PMID- 12060239
TI  - Drought stress affects chloroplast lipid metabolism in rape (Brassica napus)
      leaves.
AB  - Rape (Brassica napus L. var. Bienvenue) is a 16:3 plant which contains
      predominantly prokaryotic species of monogalactosyldiacylglycerol i.e. sn-1 C18,
      sn-2 C16 (C18/C16 MGDG). Rape plants were exposed to a restricted water supply
      for 12 days. Under drought conditions, considerable changes in lipid metabolism
      were observed. Drought stress provoked a decline in leaf polar lipids, which is
      mainly due to a decrease in MGDG content. Determination of molecular species in
      phosphatidylcholine (PC) and MGDG indicated that the prokaryotic molecular
      species of MGDG (C18/C16) decreased after drought stress while the eukaryotic
      molecular species (C18/C18) remained stable. Drought stress had different effects
      on two key enzymes of PC and MGDG synthesis. The in vitro activity of MGDG
      synthase (EC. 2.4.1.46) was reduced in drought stressed plants whereas
      cholinephosphotransferase (EC. 2.7.8.2) activity was not affected. Altogether
      these results suggest that the prokaryotic pathway leading to MGDG synthesis was
      strongly affected by drought stress while the eukaryotic pathway was not. It was
      also observed that the molecular species of leaf PC became more saturated in
      drought stressed plants. This could be due to a specific decrease in oleate
      desaturase activity.

PMID- 12060240
TI  - Scopoletin expression in elicitor-treated and tobacco mosaic virus-infected
      tobacco plants.
AB  - Localized acquired resistance (LAR) characterizes a narrow zone of living cells
      expressing strong defense responses and surrounding cells undergoing a
      hypersensitive response (HR). In Samsun NN tobacco plants, tissues undergoing
      tobacco mosaic virus-induced or elicitor-induced LAR exhibit a strong blue
      fluorescence under UV light. We have shown that scopoletin and its glucoside,
      scopolin, accounted for the fluorescence: (1) both compounds were identified
      after extraction and purification by thin layer and high performance liquid
      chromatography; (2) there was a strict correlation between the occurrence of
      fluorescence and accumulation of high amounts of scopoletin; and (3) infiltration
      of commercial scopoletin caused a similar fluorescence to that occurring in LAR
      tissues. There was a 20-fold increase in scopoletin levels in LAR tissues
      compared to tissues treated with a non-HR dose of elicitor, while PR1 protein
      accumulated in similar amounts in both types of tissues. Scopoletin was able to
      suppress the elicitor-induced HR only when co-infiltrated with very low HR-dose
      of elicitor. These two observations suggested that, although scopoletin alone
      would not be able to control the development of the HR through its known
      antioxidant activity, it may nevertheless participate to such function of LAR
      tissues in combination with other antioxidant molecules.

PMID- 12060241
TI  - Regulation of frost resistance during cold de-acclimation and re-acclimation in
      oilseed rape. A possible role of PSII redox state.
AB  - A possible role of photosynthetic apparatus during cold de-acclimation was
      studied in oilseed rape (Brassica napus var. oleifera). Plants of spring (Star)
      and winter (Gorczanski) cultivars were cold acclimated at + 5 degrees C, and de
      acclimated during 4 weeks at combinations of + 12 and + 20 degrees C operating in
      the light or/and dark, with a 12-h photoperiod. Evidence is presented that the
      photosynthetic apparatus may be involved in temperature perception during de
      acclimation. De-acclimation was faster under a 20/12 degrees C (day/night)
      treatment than under the reverse 12/20 degrees C (day/night). De-acclimation rate
      was constant when the day temperature was constant, irrespective of the night
      temperature both under cold day temperature regimes (12/20, 12/12 degrees C
      (day/night) and warm-day treatments (20/12, 20/20 degrees C (day/night). The fast
      decrease in frost resistance observed under warm-day de-acclimation was always
      accompanied by an acceleration of elongation growth. In the spring cultivar,
      elongation growth increased starting from the second week of de-acclimation,
      regardless of temperature conditions. Once elongation growth had commenced during
      de-acclimation, it continued throughout the period necessary for re-acclimation
      to low temperature. Re-acclimation to the initial freezing tolerance level was
      only possible when plant elongation was reduced. In addition re-acclimation of
      the photosynthetic apparatus to low temperature was impossible in fast growing
      plants. A possible relationship between PSII, growth rate and frost resistance
      during cold acclimation and de-acclimation is discussed.

PMID- 12060242
TI  - Reduced chilling tolerance in elongating cucumber seedling radicles is related to
      their reduced antioxidant enzyme and DPPH-radical scavenging activity.
AB  - Cucumber seedling radicles become more chilling sensitive as they elongate.
      Chilling seedlings with radicles 20 mm long for 48 h at 2.5 degrees C inhibited
      subsequent growth by 36%, while it reduced the growth of 70 mm-long radicles by
      63%. Although the growth rate of non-chilled cucumber radicles at 25 degrees C is
      constant from 20 to 80 mm, tissue viability [i.e. reduction of TTC (2,3,5
      triphenyltetrazolium chloride) to formazan] and DPPH (alpha,alpha-diphenyl-beta
      picrylhydrazyl) radical scavenging activity of apical tissue declines as radicles
      elongate from 20 to 80 mm in length. TTC reduction, DPPH-radical scavenging
      activity and protein content of apical tissue were higher in 20 than in 70 mm
      radicles immediately after chilling and after an additional 48 h of growth at 25
      degrees C. Catalase (CAT; EC 1.11.1.6) and ascorbate peroxidase (APX; EC
      1.11.1.11) activity was higher in the apical tissue of 20 than in 70 mm radicles
      before chilling. Immediately after chilling and after an additional 48 h at 25
      degrees C, superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC
      1.6.4.2), and guaiacol peroxidase (GPX; EC 1.11.1.7) activity increased more
      rapidly in 70 mm radicles than in 20 mm radicles (SOD, GR, and GPX activity in 70
      mm radicles was 1.5-, 1.9- and 8.6-fold higher, respectively, than in 20 mm
      radicles). However, APX and CAT activity in 20 mm radicles were always higher
      than in 70 mm radicles. Growth after chilling enhanced the activity of all
      antioxidant enzymes compared to that found in non-chilled tissue; however, CAT
      activity in 70 mm radicles did not recover to levels found in non-chilled tissue.
      Higher levels of CAT, APX and DPPH-radical scavenging activity are correlated
      with higher chilling tolerance of 20 mm-long cucumber radicles compared to 70 mm
      long radicles.

PMID- 12060243
TI  - Short-term effects of salt stress on antioxidant systems and leaf water relations
      of pea leaves.
AB  - In pea (Pisum sativum L.) plants the effect of short-term salt stress and
      recovery on growth, water relations and the activity of some antioxidant enzymes
      was studied. Leaf growth was interrupted by salt addition. However, during
      recovery, growth was restored, although there was a delay in returning to control
      levels. Salt stress brought about a decrease in osmotic potential and in stomatal
      conductance, but at 48 h and 24 h post-stress, respectively, both parameters
      recovered control values. In pea leaves, a linear increase in the Na+
      concentration was observed in salt treated plants. In the recovered plants, a
      slight reduction in the Na+ concentration was observed, probably due to a
      dilution effect since the plant growth was restored and the total Na+ content was
      maintined in leaves after the stress period. A significant increase of SOD
      activity occurred after 48 h of stress and after 8 h of the recovery period (53%
      and 42%, respectively), and it reached control values at 24 h post-stress. APX
      activity did not change during the stress period, and after only 8 h post-stress
      it was increased by 48% with respect to control leaves. GR showed a 71% increase
      after 24 h of salt stress and also a significant increase was observed in the
      recovered plants. A strong increase of TBARS was observed after 8 h of stress
      (180% increase), but then a rapid decrease was observed during the stress period.
      Surprisingly, TBARS again increased at 8 h post-stress (78% increase), suggesting
      that plants could perceive the elimination of NaCl from the hydroponic cultures
      as another stress during the first hours of recovery. These results suggest that
      short-term NaCl stress produces reversible effects on growth, leaf water
      relations and on SOD and APX activities. This work also suggests that both during
      the first hours of imposition of stress and during the first hours of recovery an
      oxidative stress was produced.

PMID- 12060244
TI  - Consequences of elevated CO2, augmented nitrogen-deposition and soil type on the
      soluble nitrogen and sulphur in the phloem of beech (Fagus sylvatica) and spruce
      (Picea abies) in a competitive situation.
AB  - Mixed spruce-beech plantations grown in large open-top chambers (OTC) were used
      to study consequences of elevated CO2, nitrogen-deposition and soil type on plant
      internal nitrogen and sulphur cycling of juvenile beech (Fagus sylvatica L.) and
      spruce (Picea abies Karst.) in a competitive situation. Processes of re-cycling
      as a consequence of protein turnover during leaf senescence in autumn were of
      further interest. For this purpose, phloem sap was collected in September 1998
      and analysed for the composition and concentrations of organic and inorganic
      nitrogen and sulphur compounds. The phloem exudate of spruce showed higher total
      soluble non-protein nitrogen (TSNN) concentration on calcareous soil than on
      acidic soil, independent of the treatment. N-fertilization increased the N
      concentration of phloem exudate significantly on both soil types, mainly by an
      increase of Arg and Gln concentrations. Elevated CO2 slightly increased TSNN on
      calcareous, but not on acidic soil. The combination of elevated CO2 and augmented
      N-deposition induced a further increase of TSNN on calcareous soil, but caused a
      lower N-effect on TSNN on acidic soil. Arg, the main TSNN component in phloem
      exudate, mediated this effect. Since Arg is considered to be a major nitrogen
      storage compound, it is concluded that in autumn elevated CO2 and augmented N
      deposition, influence storage of N rather than N-supply of spruce. An effect of
      elevated CO2 and augmented N-deposition on GSH and sulphate concentrations in
      phloem exudate of spruce was not observed on acidic soil. On calcareous soil
      augmented N-deposition enhanced, elevated CO2 decreased phloem exudate GSH
      contents. In combination, elevated CO2 compensated the positive effect of N
      deposition. The effects of elevated CO2 and augmented N-deposition on phloem sap
      N- and S-contents described above were not observed for beech trees. Apparently,
      elevated CO2 and augmented N-deposition did not affect plants internal S and N
      cycling of beech grown in spruce-beech plantations.

PMID- 12060245
TI  - Biomonitoring air pollution with the desert lichen Ramalina maciformis.
AB  - To investigate the environmental impact of anthropogenic activity in the Negev
      Desert, we monitored the following in order to determine the physiological
      integrity of the epilithic fruticose lichen Ramalina maciformis: (1) production
      of ethylene; (2) potential quantum yield of photosystem II expressed as
      chlorophyll fluorescence ratio Fv/Fm; and (3) electrolyte leakage of cell
      membranes in terms of electric conductivity. The degree of pollution was assessed
      by measuring the amounts of B, Cd, Co, Cu, Fe, K, Mg, Mn, Na, Ni, P, Pb, Sr and
      Zn in the lichen thallus. Some of the lichen-carrying stones collected in the
      relatively unpolluted control site were relocated on the same hill, to test the
      possible impact of relocation. An additional amount of lichen-carrying stones was
      marked as controls. The greater part of the lichen-carrying stones was
      transferred to 10 biomonitoring sites in and around Ramat Hovav, an industrial
      area in the Negev Desert, Israel. Transplanted lichen in polluted sites contained
      higher amounts of mineral elements than lichens in the control site after an
      exposure period of 7 months. Statistical analysis revealed positive correlation
      of ethylene production and Ni content, negative correlation of Fv/Fm ratios and
      B, Cu, Mn, Na, Ni, Sr and Zn, and positive correlation of electric conductivity
      and B, Mn, Ni and Sr. Both elemental content and physiological alterations in
      transferred samples of R. maciformis point to a high degree of contamination in
      Ramat Hovav. The present study suggests that the lichen R. maciformis should be
      classified as a sensitive species endangered by anthropogenic activity in the
      desert. Furthermore, this lichen species is likely to be suitable as a
      bioindicator of pollution in other parts of the Negev Desert. Ethylene production
      and electric conductivity as parameters of lichen-vitality, indicated stress in 5
      of the 12 biomonitoring sites (42%) and may therefore be considered as more
      sensitive than the Fv/Fm ratio, which indicated stress in 3 of the 12 sites
      (25%).

PMID- 12060246
TI  - Cadmium accumulation in the chloroplast of Euglena gracilis.
AB  - Intracellular distribution of Cd, cysteine, glutathione, and Cd-induced thiol
      peptides in Euglena gracilis cultured under photoheterotrophic conditions was
      studied. After 3 days of culture with 0.2 mM CdCl2, 62% of the Cd accumulated by
      cells was equally distributed between the cytosolic and chloroplastic fractions.
      However, after 8 days, metal content increased in the crude chloroplastic
      fraction to 40% of total and decreased to 19% in the cytosol; in Percoll-purified
      chloroplasts the estimated content of Cd raised to 62%. Accumulation of Cd in
      chloroplasts could be mediated by a transporter of free Cd2+, since uptake of
      added CdCl2 in isolated chloroplasts exhibited a hyperbolic type of kinetics with
      a Km of 57 &mgr;M and Vmax of 3.7 nmol (mg protein)-1 min-1. The contents of
      cysteine and glutathione markedly increased in both chloroplasts (7-19 times) and
      cytosol (4-9 times) by exposure to Cd2+, although they were always higher in the
      cytosol. Thiol-containing peptides induced by Cd were mainly located in the
      cytosol after 3 days, and in the chloroplasts after 8 days of culture. The data
      suggested that Cd was compartmentalized into chloroplasts in a process that may
      involve the transport of free Cd and the participation of thiol-peptides.

PMID- 12060247
TI  - Inhibitory effects of elevated endogenous cytokinins on nitrate reductase in ipt
      expressing tobacco are eliminated by short-term exposure to benzyladenine.
AB  - Using a novel system for expressing ipt gene from Agrobacterium tumefaciens in
      tobacco (Nicotiana tabacum L., cv. Petit Havana SR1), we were able to grow
      seedlings and teratoma-like tissue with increased content of cytokinins. This
      material enabled us to investigate new regulatory aspects of nitrate reduction.
      We grew control plants and plants with elevated cytokinins on MS media, with or
      without nitrate and benzyladenine (BA). We determined in vitro nitrate reductase
      (EC 1.6.6.1) activity (NRA) in this plant material. Initially, we found that ipt
      expressing plants always displayed lowered levels of NRA when compared to wild
      type SR1 plants. We determined that long-term exposure of tobacco plants and
      tissue to cytokinins caused up to 60% decrease in NRA. Exposure to 40 mM nitrate
      was able to induce the activity in such plants 3-fold, increasing the activity in
      SR1 plants more than 5-fold. We were able to restore wild-type levels of NRA in
      ipt-expressing plants by simultaneous induction of NR with BA and nitrate. Our
      results suggest that regulation of NR by nitrate and cytokinin is a result of
      overlaying cytokinin-driven regulatory processes, with those acting in the short
      term having a positive effect on NRA, and those acting over extended periods of
      time having inhibitory effects on NRA.

PMID- 12060248
TI  - Auxin stimulates S6 ribosomal protein phosphorylation in maize thereby affecting
      protein synthesis regulation.
AB  - Auxin is known to stimulate protein synthesis in many plant tissues, but the
      mechanisms involved in this process are unknown. The present research inquires
      whether auxin might regulate selective translation of mRNAs by inducing S6
      ribosomal protein phosphorylation on the 40S ribosomal subunit in maize (Zea mays
      L.). Maize embryonic axes auxin-stimulated by natural (IAA) or synthetic (Dicamba
      or 1-NAA) auxins, selectively increased ribosomal protein synthesis. This effect
      was not reproduced by auxin inactive analogue 2-NAA. Enhanced S6 ribosomal
      protein phosphorylation on the 40S ribosomal subunit was also observed after
      auxin stimulation, as measured by [32P] incorporation into this protein. This
      increment did not occur when stimulation was performed with the inactive auxin
      analogue. Further, increased recruitment into polysomes of two 5'TOP-like mRNAs,
      encoding for the initiation translation factor eIF-iso4E and the S6 ribosomal
      protein, was also found after auxin stimulation of maize axes. A positive
      correlation was established between the levels of S6 ribosomal protein
      phosphorylation and the S6 ribosomal protein transcript recruitment into
      polysomes by means of okadaic acid or heat shock application to maize axes. These
      data indicate that auxin stimulates S6 ribosomal protein phosphorylation on maize
      ribosomes, concomitant to the recruitment of specific mRNAs (5'TOP-like mRNAs)
      into polysomes for translation. It is proposed that by this mechanism auxin
      regulate the synthesis of specific proteins in maize tissues.

PMID- 12060249
TI  - Vernalization, photoperiod and GA3 interact to affect flowering of Japanese
      radish (Raphanus sativus Chinese Radish Jumbo Scarlet).
AB  - Raphanus sativus L. Chinese Radish Jumbo Scarlet has characteristics that make it
      an excellent plant model for vernalization studies. This study further
      characterizes flower induction of R. sativus Chinese Radish Jumbo Scarlet. Seed
      were imbibed in distilled water containing 0, 10-5 M or 10-3 M GA3 for 24 h and
      were then exposed to 6 +/- 0.5 degrees C (vernalized) for 0, 2, 4, 6, or 8 days.
      Seedlings were then grown under a short- (8 h) or long-day photoperiod (8 h with
      or without a 4-h night interruption; 2200-0200 h). Of unvernalized plants grown
      under long- and short-day conditions, 45 and 3% flowered, respectively.
      Saturation of the vernalization response occurred after a 4- or 8-day
      vernalization treatment when plants were placed under long- or short-days,
      respectively. Basal leaf number and days to anthesis decreased when seeds were
      cooled for 2 or 4 days and were imbibed with 10-3 M GA3 compared to distilled
      water only. These data indicate that R. sativus Chinese Jumbo Scarlet has
      principally an obligate vernalization requirement when grown under short-days.
      GA3 application only facilitated flowering when the length of the vernalization
      treatment was marginal. Taken together, these data support the use of this plant
      as a model plant for identifying vernalization responses under short-day
      conditions.

PMID- 12060250
TI  - In situ analysis of enzymes involved in sucrose to hexose-phosphate conversion
      during stolon-to-tuber transition of potato.
AB  - An in situ study of enzymes involved in sucrose to hexose-phosphate conversion
      during in vitro stolon-to-tuber transition of potato (Solanum tuberosum L. cv.
      Bintje) was employed to follow developmental changes in spatial patterns. In situ
      activity of the respective enzymes was visualized by specific activity-staining
      techniques and they revealed distinct spatially and developmentally regulated
      patterns. Two of the enzymes studied were also subject to in situ investigations
      at the transcriptional level. During the stages of stolon formation high
      hexokinase (EC 2.7.1.1) and acid (cell wall-bound) invertase (EC 3.2.1.26)
      activities were restricted to the mitotically active (sub)apical region,
      suggesting a possible importance of these enzymes for cell division. At the onset
      of tuberization sucrose synthase (EC 2.4.1.13) and fructokinase (EC 2.7.1.4) were
      strongly induced (visualized at transcriptional and translational level) and the
      acid invertase activities disappeared from the swelling subapical region as
      expected. The high degree of similarity in the spatial pattern and the temporal
      induction of sucrose synthase and fructokinase suggests a tightly co-ordinated
      coarse (up)regulation, which may be subject to a sugar-modulated mechanism(s) by
      which genes involved in the metabolic sucrose-starch converting potential are co
      ordinately regulated during tuber growth. The overall activity of uridine-5
      diphosphoglucose pyrophosphorylase (EC 2.7.7.9) was present in all tissues during
      stolon and tuber development, implying that its coarse control is not subject to
      (in)direct developmental regulation.

PMID- 12060251
TI  - Uncoupling brassinosteroid levels and de-etiolation in pea.
AB  - The suggestion that brassinosteroids (BRs) have a negative regulatory role in de
      etiolation is based largely on correlative evidence, which includes the de
      etiolated phenotypes of, and increased expression of light-regulated genes in,
      dark-grown mutants defective in BR biosynthesis or response. However, we have
      obtained the first direct evidence which shows that endogenous BR levels in light
      grown pea seedlings are increased, not decreased, in comparison with those grown
      in the dark. Similarly, we found no evidence of a decrease in castasterone (CS)
      levels in seedlings that were transferred from the dark to the light for 24 h.
      Furthermore, CS levels in the constitutively de-etiolated lip1 mutant are similar
      to those in wild-type plants, and are not reduced as is the case in the BR
      deficient lkb plants. Unlike lip1, the pea BR-deficient mutants lk and lkb are
      not de-etiolated at the morphological or molecular level, as they exhibit neither
      a de-etiolated phenotype or altered expression of light-regulated genes when
      grown in the dark. Similarly, dark-grown WT plants treated with the BR
      biosynthesis inhibitor, Brz, do not exhibit a de-etiolated phenotype. In
      addition, analysis of the lip1lkb double mutant revealed an additive phenotype
      indicative of the two genes acting in independent pathways. Together these
      results strongly suggest that BR levels do not play a negative-regulatory role in
      de-etiolation in pea.

PMID- 12060252
TI  - Identification and quantification of three active auxins in different tissues of
      Tropaeolum majus.
AB  - Indole-3-acetic acid (IAA), indole-3-butyric acid (IBA) and phenylacetic acid
      (PAA) were identified as endogenous compounds with auxin activity in nasturtium
      (Tropaeolum majus L.) by full scan gas chromatography-mass spectrometry. The
      endogenous concentrations of the three auxins were measured by GC-selected ion
      monitoring-MS and isotope dilution analysis using stable labelled isotopes. PAA
      was present at concentrations about 10- to 100-fold lower than IAA, whereas IBA
      was found to be in the same concentration range as IAA. Free IAA was highest in
      roots followed by young leaves. IBA was also highest in the roots, and relatively
      high concentrations were found in young leaves and flowers. The distribution of
      PAA was quite different from that found for IBA. No PAA could be detected in
      young leaves and flowers, and in all other tissues studied the concentrations
      were well below those of the other two auxin compounds. The presence of a
      nitrilase gene family and nitrilase activity in extracts from T. majus suggests
      that PAA might be synthesized by the nitrilase pathway using benzylglucosinolate
      as precursor.

PMID- 12060253
TI  - Erratum.

PMID- 12060254
TI  - What are the driving forces for water lifting in the xylem conduit?
AB  - After Renner had shown convincingly in 1925 that the transpirational water loss
      generates tensions larger than 0.1 MPa (i.e. negative pressures) in the xylem of
      cut leafy twigs the Cohesion Theory proposed by Bohm, Askenasy, Dixon and Joly at
      the end of the 19th century was immediately accepted by plant physiologists.
      Introduction of the pressure chamber technique by Scholander et al. in 1965
      enforced the general belief that tension is the only driving force for water
      lifting although substantial criticism regarding the technique and/or the
      Cohesion Theory was published by several authors. As typical for scientific
      disciplines, the advent of minimal- and non-invasive techniques in the last
      decade as well as the development of a new, reliable method for xylem sap
      sampling have challenged this view. Today, xylem pressure gradients, potentials,
      ion concentrations and volume flows as well as cell turgor pressure gradients can
      be monitored online in intact transpiring higher plants, and within a given
      physiological context by using the pressure probe technique and high-resolution
      NMR imaging techniques, respectively. Application of the pressure probe technique
      to transpiring plants has shown that negative absolute pressures (down to - 0.6
      MPa) and pressure gradients can exist temporarily in the xylem conduit, but that
      the magnitude and (occasionally) direction of gradients contrasts frequently the
      belief that tension is the only driving force. This seems to be particularly the
      case for plants faced with problems of height, drought, freezing and salinity as
      well as with cavitation of the tensile water. Reviewing the current data base
      shows that other forces come into operation when exclusively tension fails to
      lift water against gravity due to environmental conditions. Possible candidates
      are longitudinal cellular and xylem osmotic pressure gradients, axial potential
      gradients in the vessels as well as gel- and gas bubble-supported interfacial
      gradients. The multiforce theory overcomes the problem of the Cohesion Theory
      that life on earth depends on water being in a highly metastable state.

PMID- 12060255
TI  - The dose-response curve of the gravitropic reaction: a re-analysis.
AB  - The dose-response curve of the gravitropic reaction is often used to evaluate the
      gravisensing of plant organs. It has been proposed (Larsen 1957) that the
      response (curvature) varies linearly as a function of the logarithm of the dose
      of gravistimulus. As this model fitted correctly most of the data obtained in the
      literature, the presentation time (tp, minimal duration of stimulation in the
      gravitational field to induce a response) or the presentation dose (dp, minimal
      quantity in g.s of stimulation to induce a response) were estimated by
      extrapolating down to zero curvature the straight line representing the response
      as a function of the logarithm of the stimulus. This method was preferred to a
      direct measurement of dp or tp with minute stimulations, since very slight
      gravitropic response cannot be distinguished from the background oscillations of
      the extremity of the organs. In the present review, it is shown that generally
      the logarithmic model (L) does not fit the experimental data published in the
      literature as well as the hyperbolic model (H). The H model in its simplest form
      is related to a response in which a ligand-receptor system is the limiting phase
      in the cascade of events leading to the response (Weyers et al. 1987). However,
      it is demonstrated that the differential growth, responsible for the curvature
      (and the angle of curvature), would vary as a hyperbolic function of the dose of
      stimulation, even if several steps involving ligand-receptor systems are
      responsible for the gravitropic curvature. In the H model, there is theoretically
      no presentation time (or presentation dose) since the curve passes through the
      origin. The value of the derivative of the H function equals a/b and represents
      the slope of the cune at the origin. It could be therefore used to estimate
      gravisensitivity. This provides a measurement of graviresponsiveness for
      threshold doses of stimulation. These results imply that the presentation time
      (or presentation dose) derived from the L model cannot be used anymore as an
      estimate of gravisensitivity. On the contrary, the perception time (minimal
      duration of a repeated stimulation which induces a response), which is less than
      1 s, should be related to the perception of gravity. The consequences of these
      results on the mode of action and the nature of graviperception are discussed.

PMID- 12060256
TI  - Lignification related enzymes in Picea abies suspension cultures.
AB  - Activity of a number of enzymes related to lignin formation was measured in a
      Picea abies (L) Karsten suspension culture that is able to produce native-like
      lignin into the nutrient medium. This cell culture is an attractive model for
      studying lignin formation, as the process takes place independently of the
      complex macromolecular matrix of the native apoplast. Suspension culture proteins
      were fractionated into soluble cellular proteins, ionically and covalently bound
      cell wall proteins and nutrient medium proteins. The nutrient medium contained up
      to 5.3% of total coniferyl alcohol peroxidase (EC 1.11.1.7) activity and a
      significant NADH oxidase activity that is suggested to be responsible for
      hydrogen peroxide (H2O2) production. There also existed some malate dehydrogenase
      (EC 1.1.1.37) activity in the apoplast of suspension culture cells (in ionically
      and covalently bound cell wall protein fractions), possibly for the regeneration
      of NADH that is needed for peroxidase-catalysed H2O2 production. However, there
      is no proof of the existence of NADH in the apoplast. Nutrient medium peroxidases
      could be classified into acidic, slightly basic and highly basic isoenzyme groups
      by isoelectric focusing. Only acidic peroxidases were found in the covalently
      bound cell wall protein fraction. Several peroxidase isoenzymes across the whole
      pI range were detected in the protein fraction ionically bound to cell walls and
      in the soluble cellular protein fraction. One laccase-like isoenzyme with pI of
      approximately 8.5 was found in the nutrient medium that was able to form
      dehydrogenation polymer from coniferyl alcohol in the absence of H2O2. The total
      activity of this oxidase towards coniferyl alcohol was, however, several orders
      of magnitude smaller than that of peroxidases in vitro. According to 2D 1H-13C
      correlation NMR spectra, most of the abundant structural units of native lignin
      and released suspension culture lignin are present in the oxidase produced
      dehydrogenation polymer but in somewhat different amounts compared to peroxidase
      derived synthetic lignin preparations. A coniferin beta-glucosidase (EC 3.2.1.21)
      was observed to be secreted into the culture medium.

PMID- 12060257
TI  - Seasonal pattern of monoterpene synthase activities in leaves of the evergreen
      tree Quercus ilex.
AB  - Monoterpene synthase activities were measured in current year and 1-year-old
      leaves of holm oak (Quercus ilex L.). The monoterpene synthase activities of the
      leaves strongly changed with leaf development and leaf age. Enzyme activities
      increased rapidly in spring after leaf emergence, reaching maximum values in
      summer, which declined during the following winter period. In the next spring
      monoterpene synthase activities recovered in the old leaves to about one-third of
      values in the previous years and showed a similar seasonal variation as in young
      leaves. In both leaf age classes the pattern of enzymatic monoterpene formation
      was stable with alpha-pinene (33%), beta-pinene (28%), and myrcene (26%) as
      prominent compounds followed by minor fractions of sabinene (10%) and limonene
      (3%). Monoterpene emission correlated with the activity of the synthetizing
      enzymes, indicating that monoterpene synthase activities in Q. ilex reflect the
      seasonal monoterpene emission potential of the leaves.

PMID- 12060258
TI  - Purification and characterization of the raffinose oligosaccharide chain
      elongation enzyme, galactan : galactan galactosyltransferase (GGT), from Ajuga
      reptans leaves.
AB  - Galactan: galactan galactosyltransferase (GGT), an enzyme involved in the
      biosynthesis of the long-chain raffinose family of oligosaccharides (RFOs) in
      Ajuga reptans, catalyses the transfer of an alpha-galactosyl residue from one
      molecule of RFO to another one resulting in the next higher RFO oligomer. This
      novel galactinol (alpha-galactosyl-myo-inositol)-independent alpha
      galactosyltransferase is responsible for the accumulation of long-chain RFOs in
      vivo. Warm treatment (20 degrees C) of excised leaves resulted in a 34-fold
      increase of RFO concentration and a 200-fold increase of GGT activity after 28
      days. Cold treatment (10 degrees C/3 degrees C day/night) resulted in a 26- and
      130-fold increase, respectively. These data support the role of GGT as a key
      enzyme in the synthesis and accumulation of long-chain RFOs. GGT was purified
      from leaves in a 4-step procedure which involved fractionated precipitation with
      ammonium sulphate as well as lectin affinity, anion exchange, and size-exclusion
      chromatography and resulted in a 200-fold purification. Purified GGT had an
      isoelectric point of 4.7, a pH optimum around 5, and its transferase reaction
      displayed saturable concentration dependence for both raffinose (Km = 42 mM) and
      stachyose (Km = 58 mM). GGT is a glycoprotein with a 10% glycan portion. The
      native molecular mass was 212 kDa as determined by size-exclusion chromatography.
      Purified GGT showed one single active band after native PAGE or IEF separation,
      respectively, which separated into three bands on SDS-PAGE at 48 kDa, 66 kDa, and
      60 kDa. The amino acid sequence of four tryptic peptides obtained from the major
      48-kDa band showed a high homology to plant alpha-galactosidase (EC 3.2.1.22)
      sequences. GGT differed, however, in its substrate specificity from alpha
      galactosidases; it neither hydrolysed nor transferred alpha-galactosyl-groups
      from melibiose, galactinol, UDP-galactose, manninotriose, and manninotetrose.
      Galactinol, sucrose, and galactose inhibited the GGT reaction considerably at 10
      50 mM.

PMID- 12060259
TI  - Sucrose metabolism and cellulose biosynthesis in sunflower hypocotyls.
AB  - The relationships between cellulose accumulation, changes in specific activities
      of enzymes of sucrose catabolism, levels of UDP-glucose and rate of dark
      respiration were investigated in the subapical 1 cm-hypocotyl region of 10- to 14
      day-old-sunflower seedlings (Helianthus annuus L). The plants were grown under a
      light/dark regime in vermiculite that was soaked either with distilled water or
      half-strength Hoagland nutrient solution. At this stage of seedling development,
      the hypocotyl had ceased to elongate but increased in width. Stem thickening and
      the rate of cellulose accumulation were promoted by nutrient solution. The levels
      of the soluble (vacuolar) and wall-associated acid invertases (EC 3.2.1.26) were
      not correlated with these processes. However, the activities of the soluble
      (cytoplasmic) and membrane-bound sucrose synthases (EC 2.4.1.13) were larger in
      hypocotyls that were grown in the presence of nutrient solution. The
      concentration of UDP-glucose was reduced, and the rate of dark respiration was
      enhanced in the hypocotyls that were grown in Hoagland solution. The results
      support the hypothesis that both forms of the enzyme sucrose synthase play a
      critical role in cellulose biosynthesis of hypocotyl cells that had ceased to
      elongate and continue to grow by wall thickening.

PMID- 12060260
TI  - Effect of drought and high solar radiation on 1-aminocyclopropane-1-carboxylic
      acid and abscisic acid concentrations in Rosmarinus officinalis plants.
AB  - The endogenous concentrations of ACC and ABA were measured, at predawn and at
      maximum solar radiation, during a summer drought, and recovery after autumn
      rainfalls, in rosemary (Rosmarinus officinalis L.), a drought-tolerant species,
      growing under Mediterranean field conditions. During the summer, plants were
      subjected to both water deficit and high solar radiation. Plants showed severe
      reductions in shoot water potential to -3 MPa, which were associated with drastic
      stomatal closure (73%), a decrease in net photosynthesis, reaching almost zero,
      and a severe chlorophyll loss (74%). Despite the severity of the stress, plants
      recovered after the autumn rainfalls. The concentration of ACC was not enhanced
      by drought, and at predawn these concentrations remained constant at
      approximately 600 pmol ACC-1 DW throughout the experiment. Thus, ethylene did not
      regulate the response of rosemary to drought. However, a sharp increase in ACC
      levels between predawn and midday was observed. This increase was positively
      correlated to the intensity of the incident solar radiation. ACC levels recorded
      in June at midday reached 16 000 pmol g DW and in October values of 1000 pmol g-1
      DW were observed. In contrast, in drought-stressed plants predawn concentrations
      of ABA were up to 130-fold those of recovered plants, and the levels of ABA
      scored at midday were double of those scored at predawn. In conclusion, although
      drought-stressed rosemary plants showed a relatively moderate ABA accumulation
      (approximately 500 pmol g-1 DW#, at predawn), it seems to be an essential factor
      for the regulation of the plant response to stress, thereby enabling a rapid
      recovery after stress release, although other mechanisms can not be excluded. As
      drought stress did not induce ACC accumulation, it was concluded that ethylene
      production was not a major factor in the drought stress resistance of rosemary
      plants. The increased ACC and ABA concentrations at midday were correlated with
      day length and light intensity and not with the water status of the plant.

PMID- 12060261
TI  - Ozone tolerance in snap bean is associated with elevated ascorbic acid in the
      leaf apoplast.
AB  - Ascorbic acid (AA) in the leaf apoplast has the potential to limit ozone injury
      by participating in reactions that detoxify ozone and reactive oxygen
      intermediates and thus prevent plasma membrane damage. Genotypes of snap bean
      (Phaseolus vulgaris L) were compared in controlled environments and in open-top
      field chambers to assess the relationship between extracellular AA content and
      ozone tolerance. Vacuum infiltration methods were employed to separate leaf AA
      into extracellular and intracellular fractions. For plants grown in controlled
      environments at low ozone concentration (4 nmol mol-1 ozone), leaf apoplast AA
      was significantly higher in tolerant genotypes (300-400 nmol g-1 FW) compared
      with sensitive genotypes (approximately 50 nmol g-1 FW), evidence that ozone
      tolerance is associated with elevated extracellular AA. For the open top chamber
      study, plants were grown in pots under charcoal-filtered air (CF) conditions and
      then either maintained under CF conditions (29 nmol mol-1 ozone) or exposed to
      elevated ozone (67 nmol mol-1 ozone). Following an 8-day treatment period, leaf
      apoplast AA was in the range of 100-190 nmol g-1 FW for all genotypes, but no
      relationship was observed between apoplast AA content and ozone tolerance. The
      contrasting results in the two studies demonstrated a potential limitation in the
      interpretation of extracellular AA data. Apoplast AA levels presumably reflect
      the steady-state condition between supply from the cytoplasm and utilization
      within the cell wall. The capacity to detoxify ozone in the extracellular space
      may be underestimated under elevated ozone conditions where the dynamics of AA
      supply and utilization are not adequately represented by a steady-state
      measurement.

PMID- 12060262
TI  - Retardation and inhibition of the cation-induced superoxide generation in BY-2
      tobacco cell suspension culture by Zn2+ and Mn2+
AB  - Salts at high concentrations may cause oxidative damage to plant cells since many
      studies indicated the involvement of reactive oxygen species in salt-stress
      response. Recently, we have demonstrated that treatment of tobacco (Nicotiana
      tabacum) cell suspension culture with various salts result in an immediate burst
      of superoxide production via activation of NADPH oxidase by ions of alkali metals
      (Li+, Na+, K+), alkali earth metals (Mg2+, Ca2+) or lanthanides (La3+, Gd3+). In
      this study, we tested the effect of extracellular supplementation of Zn2+ and
      Mn2+ on the cation-induced oxidative burst in tobacco cell suspension culture,
      measured with a superoxide-specific Cypridina luciferin-derived chemiluminescent
      reagent. Extracellular supplementation of Zn2+ and Mn2+ inhibited the generation
      of superoxide in response to addition of salts. Although both Zn2+ and Mn2+
      inhibited the salt-induced generation of superoxide, the modes of inhibition by
      those ions seemed to be different since Mn2+ simply inhibited total production of
      superoxide while Zn2+ inhibited the early phase of superoxide production and
      induced the slow release of superoxide. Roles of Mn2+ and Zn2+ in protection of
      plant cells from salt stress, as an effective superoxide scavenger and an
      effective inhibitor of plasma membrane-bound NADPH oxidase, respectively, are
      discussed.

PMID- 12060263
TI  - Effects of salinity stress on photosystem II function in cyanobacterial Spirulina
      platensis cells.
AB  - The changes in PSII photochemistry in Spirulina platensis cells exposed to
      salinity stress (0-0.8 M NaCl) for 12 h were studied. Salinity stress induced a
      decrease in oxygen evolution activity, which correlated with the decrease in the
      quantum yield of PSII electron transport (PhiPSII). Phycocyanin content decreased
      significantly while chlorophyll content remained unchanged in salt-stressed
      cells. Salinity stress induced an increase in non-photochemical quenching (qN)
      and a decrease in photochemical quenching (qP). Analyses of the polyphasic
      fluorescence transients (OJIP) showed that with the increase in salt
      concentration, the fluorescence yield at the phases J, I and P declined sharply
      and the transient almost levelled off at salt concentration of 0.8 M NaCl. The
      effects of DCMU on the polyphasic rise of fluorescence transients decreased
      significantly. Salinity stress resulted in a decrease in the efficiency of
      electron transfer from QA- to QB. The slope at the origin of the relative
      variable fluorescence curves (dV/dto) and the relative variable fluorescence at
      phase J (VJ) increased in the absence of DCMU, but decreased in the presence of
      DCMU. The shape of the relative variable fluorescence transients in salt-stressed
      cells was comparable to that of the control cells incubated with DCMU. The
      results in this study suggest that salt stress inhibited the electron transport
      at both donor and acceptor sides of PSII, resulted in damage to phycobilisome and
      shifted the distribution of excitation energy in favour of PSI.

PMID- 12060264
TI  - Studies on water transport through the sweet cherry fruit surface: III.
      Conductance of the cuticle in relation to fruit size.
AB  - Rain-cracking of sweet cherry fruit has been related to water absorption through
      the fruit surface and large fruit has been reported to be more susceptible to
      cracking than small fruit. Therefore, the effect of fruit size on water
      conductance of the cuticular membrane (CM) of exocarp segments excised from
      cheek, suture or stylar end region of mature sweet cherry fruit (Prunus avium L.
      cv. Sam) was investigated. Segments consisting of epidermis, hypodermis and
      several layers of mesocarp cells were mounted in diffusion cells filled with
      deionized water. Mass loss due to transpiration was monitored gravimetrically
      during an 8-h incubation period (25 +/- 2 degrees C) over dry silica in the dark.
      Conductance was calculated from the amount of water transpired per unit surface
      area and time divided by the difference in water vapour concentration across the
      segment. For an average size cv. Sam sweet cherry CM conductance was 1.06 x 10-4,
      0.91 x 10-4 and 2.09 x 10-4 m s-1 in cheek, suture and stylar end region,
      respectively. Fruit size had no significant effect on conductance in cheek or
      suture regions, but for the stylar end region conductance was positively related
      to fruit size. Stomatal density in the cheek, but not the suture or stylar end
      region increased as fruit size increased. The area of the stylar scar was
      positively related to fruit size. Conductance of the stylar scar averaged 37.6 +/
      4.0 x 10-4 m s-1 and was 54-fold higher than that of the CM between stomata in
      the cheek region (mean 0.69 x 10-4 m s-1). Conductance calculated on a whole
      fruit basis is estimated to increase by 108% as fruit size increases from 6 to 12
      g. Increased conductance on a whole fruit basis may be attributed to increased
      fruit surface area and increased conductance per unit fruit surface area,
      particularly in the stylar end region.

PMID- 12060265
TI  - Joint action of phenolic acid mixtures and its significance in allelopathy
      research.
AB  - Although the ecological significance of mixtures of phytotoxins is recognized in
      research on chemical plant interference (allelopathy), few studies convincingly
      demonstrate the joint action of phytotoxin mixtures, key to understanding the
      ecological impact of these materials, using established models from other
      biological disciplines, e.g. toxicology and pharmacology. Addressing this need,
      the present study investigates the joint action of the phenolic acids, p
      hydroxybenzoic, p-coumaric and ferulic acids on root growth inhibition of
      perennial ryegrass (Lolium perenne L). The Additive Dose Model (ADM) isobole and
      estimated concentration of phenolic acid mixture were calculated on ED20, ED50
      and ED80 from the dose-response curves for the phenolic acids applied alone or in
      mixtures of fixed ratios. The binary combination of three selected phenolic acids
      is generally antagonistic relative to the ADM. No evidence for synergistic
      activities of phenolic acids in the mixture was noted. Since allelopathic
      activities in nature are largely due to the presence of several compounds in a
      mixture, the present study advances understanding of the joint action of binary
      combination of allelochemicals in a mixture.

PMID- 12060266
TI  - Genetic transformation of cauliflower (Brassica oleracea var. botrytis) by direct
      DNA uptake into mesophyll protoplasts.
AB  - Mesophyll protoplasts of Brassica oleracea var. botrytis were successfully
      transformed using polyethylene glycol (PEG). The success of plant transformation
      depended on both gene transfer and plant regeneration. Parameters, such as PEG
      and vector concentrations and heat shock conditions were tested in experiments on
      transient expression of the beta-glucuronidase (EC 3.2.1.31) gene and the most
      suitable conditions for DNA uptake were determined. Two antibiotic resistance
      marker genes for neomycin phosphotransferase (EC 2.7.1.95) and hygromycin
      phosphotransferase (EC 2.7.1.104), and three vector plasmids with different
      lengths were used to obtain stable transformants.

PMID- 12060267
TI  - Up-regulation of arginine decarboxylase gene expression and accumulation of
      polyamines in mustard (Brassica juncea)in response to stress.
AB  - Arginine decarboxylase (ADC) is a key enzyme involved in the synthesis of
      polyamines, which have been implicated in a wide range of plant responses,
      including stress. However, regulation of polyamine levels in relation to ADC in
      response to stress at the molecular level is not well understood. In an attempt
      to address this question, we first cloned two cDNAs in mustard (Brassica
      juncea[L.] Czern & Coss var. Indian Mustard), designated MADC2 and MADC3,
      encoding predicted ADC. MADC2 and MADC3 encode polypeptides of 692 and 680 amino
      acid residues, respectively. A comparison of deduced amino acid sequence revealed
      that both were highly homologous to MADC1 (77%), a mustard ADC, and other plant
      ADCs (63-84%). Northern analysis revealed that ADC transcripts in mustard were
      generally more abundant in stem and root but were barely detectable in leaf.
      However, ADC expression in the leaf was up-regulated differentially in response
      to stress such as chilling, salt and mannitol and to treatments with exogenous
      polyamines. While chilling induced expression of all three ADC genes, salt
      predominantly resulted in increased accumulation of MADC3 transcript. Leaves
      exhibited a similar response to exogenous putrescine, spermidine and spermine,
      all of which stimulated accumulation of MADC2 and MADC3 transcripts but not
      MADC1. Furthermore, exogenous putrescine also increased the endogenous levels of
      spermidine and spermine, while a higher endogenous putrescine and spermidine
      content was detected in leaf incubated with exogenous spermine. Leaves also
      responded to chilling, salt and mannitol by increasing the levels of the cellular
      polyamine content, in which the level of spermine in free and conjugated forms
      increased most profoundly.

PMID- 12060268
TI  - Foliar phenolic composition of European white birch during bud unfolding and leaf
      development.
AB  - We studied the between-tree and within-tree variation in the composition and
      content of foliar low-molecular-weight phenolics (LMWP) of European white birch
      (Betula pendula Roth) during the unfolding of vegetative buds and during early
      leaf development. In buds, the major groups of phenolic compounds were
      hydrolysable tannins and flavonoid aglycones, whereas, later during leaf
      development, the flavonoid glycosides accounted for most of the total LMWP. The
      content of total LMWP, as well as individual compounds, varied largely among
      individual trees, while variation within an individual tree was low. The
      biosynthetic origin of individual compounds or compound groups is discussed in
      order to explain the main patterns in leaf chemistry during bud unfolding and
      early leaf development.

PMID- 12060269
TI  - Developmental regulation of H+-ATPase-dependent auxin responses in the
      diageotropica mutant of tomato (Lycopersicon esculentum).
AB  - Rapid auxin effects on H+ pumping across the plasma membrane precede auxin
      induced elongation growth of hypocotyls and swelling of guard cells, as well as
      auxin inhibition of root growth. To investigate whether auxin-signalling
      mechanisms in such diverse cell types are similar, we characterized these
      responses in various tissues of the diageotropica (dgt) mutant of tomato
      (Lycopersicon esculentum Mill.). Abraded hypocotyl segments of 4-day-old,
      etiolated dgt seedlings showed an impaired H+ secretion response to applied
      auxin. mRNA levels for two PM H+-ATPase isoforms, LHA2 and LHA4, were not reduced
      in dgt hypocotyl segments as compared to wild-type segments, suggesting that the
      dgt mutation does not affect H+ secretion by reducing the transcription of major
      PM H+-ATPase genes. The dgt mutation also disrupted auxin inhibition of growth
      and H+ secretion in roots of 4-day-old dgt seedlings. However, immediately after
      germination, dgt seedling roots responded to auxin with a near-normal inhibition
      of growth. In addition, stomata in epidermal peels from 2-week-old dgt cotyledons
      demonstrated normal auxin-induced opening. We conclude that an intact DGT gene
      product is required for auxin-induced H+ secretion in tomato hypocotyl segments
      and for auxin inhibition of H+ secretion in roots of older seedlings, but that a
      DGT-independent pathway for auxin responses exists in young root tips and in
      guard cells. A developmentally controlled switch from DGT-independent to DGT
      dependent auxin signalling appears to take place in root tips within 2 days after
      germination.

PMID- 12060270
TI  - Peach (Prunus persica) fruit ripening: aminoethoxyvinylglycine (AVG) and
      exogenous polyamines affect ethylene emission and flesh firmness.
AB  - The effect of various concentrations of aminoethoxyvinylglycine (AVG; 0.32 and
      1.28 mM), an ethylene biosynthesis inhibitor, and of the polyamines putrescine
      (10 mM), spermidine (0.1, 1 and 5 mM) and spermine (2 mM) on peach (Prunus
      persica L. Batsch cv. Redhaven) fruit ripening was evaluated under field
      conditions. Treatments were performed 19 (polyamines) and 8 (AVG) days before
      harvest. Fruit growth (diameter, fresh and dry weight), flesh firmness, soluble
      solids content and ethylene emission were determined on treated and untreated
      (controls) fruits. Moreover, endogenous polyamine content and S
      adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.21) activity were determined to
      check for a possible competition between polyamines and ethylene for their common
      precursor S-adenosylmethionine (SAM). Both treatments strongly inhibited ethylene
      emission and delayed flesh softening. On a biochemical level, AVG and exogenous
      polyamines both reduced the free-to-conjugate ratio of endogenous polyamines, and
      transiently altered SAMDC activity. The possible use of these compounds to
      control fruit ripening is discussed also in the light of their rejuvenating
      effect on peach fruits.

PMID- 12060271
TI  - Molecular cloning of a functional protein phosphatase 2C (FsPP2C2) with unusual
      features and synergistically up-regulated by ABA and calcium in dormant seeds of
      Fagus sylvatica.
AB  - Phosphorylation/dephosphorylation of proteins is a general mechanism of hormonal
      signal transduction, including ABA, and serine/threonine protein phosphatases 2C
      (PP2C, EC 3.1.3.16) have been suggested to play an important role in this
      process. By means of differential reverse transcriptase-polymerase chain reaction
      (RT-PCR) and further screening of a cDNA library made from mRNA of ABA-treated
      Fagus sylvatica L. seeds, a full-length cDNA clone (FsPP2C2) encoding a putative
      PP2C was obtained. Comparison to the databases revealed high homology to plant
      PP2C and most features of these enzymes, but unusual characteristics were found
      within the catalytic domain and the N-terminal region of the amino acid sequence.
      The coding region of FsPP2C2 was expressed in Escherichia coli as histidine tag
      fusion protein and shows Mg2+-dependent in vitro phosphatase activity.
      Transcription of the FsPP2C2 gene is low during seeds stratification at 4 degrees
      C or under gibberellic acid (GA3) treatment and clearly increases when seeds are
      treated with ABA and calcium (Ca2+) together, while the addition of calcium
      chelators (EGTA or TMB-8) decreases its expression. Furthermore, FsPP2C2 is only
      expressed in ABA-treated tissues, preferentially in seeds, which suggests that
      this PP2C is specifically induced by ABA in dormant seeds, in a Ca2+-dependent
      manner, and also in other ABA-treated tissues.

PMID- 12060272
TI  - Limited acclimation of photosynthesis to blue light in the seaweed Gracilaria
      tenuistipitata.
AB  - Changes in photosynthetic capacity of the seaweed Gracilaria tenuistipitata Zhang
      et Xia acclimated to monochromatic blue light were studied. For this purpose,
      affinity for external inorganic carbon, light use efficiency, carbonic anhydrase
      (CA; EC 4.2.1.1) activity and content of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco; EC 4.1.1.39) were determined in thalli acclimated
      to 45 &mgr;mol m-2 s-1 of blue light. Thalli cultured in white light of the same
      photon fluence rate were used as a control. Lower maximal photosynthetic rates
      (i.e. at light and carbon saturation) were obtained in the thalli cultured in
      blue light. Apparently, this lower photosynthetic capacity was not due to
      differences in affinity and/or capacity for use of external dissolved inorganic
      carbon (DIC) since (1) CA activity did not change significantly and (2) similar
      values of photosynthetic conductance for DIC at alkaline pH were obtained (0.95 x
      10-6 m s-1). In addition, the pool size of Rubisco was not modified by the blue
      light treatment since there were no significant differences in Rubisco content
      between white (12.14% of soluble proteins) and blue light (12.13% of soluble
      proteins) treatments. In contrast, Fv/Fm was increased by 11% and photosynthetic
      efficiency for oxygen production was reduced by 50% in blue light. This absence
      of correlation between quantum yields for maximum stable charge separation of
      photosystem II and oxygen evolution suggests that blue light promote changes in
      rates of photosynthetic electron flow.

PMID- 12060273
TI  - An aquatic perspective on the concepts of Ingestad relating plant nutrition to
      plant growth.
AB  - The Ingestad approach to the culture of higher terrestrial plants for
      physiological studies is discussed in relation to a number of resources,
      organisms and growth situations that were not part of the original design and
      rationale of Ingestad's methodology. The additional resource considered is
      photosynthetically active radiation, and difficulties of applying the Ingestad
      approach to this resource as well as to atmospheric CO2 are considered. The
      relationship of the Ingestad approach to reductionist studies based on enzyme
      kinetic studies is then briefly considered. The organisms considered next are
      aquatic plants, including both micro- and macrophytes. The consideration of
      photosynthetic microorganisms leads to a comparison of the Ingestad approach with
      growth in batch, and in continuous (chemostat and turbidostat) cultures, and with
      studies on growth in synchronous cultures in which cyclic changes in cell
      composition in the cell growth and division cycle can be identified. The natural
      environmental conditions for these organisms are a natural extension of the
      light/dark synchronization of laboratory cultures, and the bloom (batch culture
      equivalent to new production) and of grazing and parasitism removing biomass and
      recycling nutrients (chemostat or turbidostat culture equivalent to recycled
      production) situations for phytoplankton. The overall conclusion is that, while
      the Ingestad approach is a useful mirror in which to examine other concepts of
      plant resource acquisition and manipulation, the Ingestad methodology seems to
      make assumptions about the intrinsic growth rate and composition of plants that
      cannot be independently verified.

PMID- 12060274
TI  - Sprouting of the fructan- and starch-storing geophyte Lachenalia minima: Effects
      on carbohydrate and water content within the bulbs.
AB  - The carbohydrate pool within the bulbs of Lachenalia minima W.F. Barker
      (Hyacinthaceae) consists of similar amounts of fructans and starch. This study
      was conducted to examine the changes within the pool of non-structural
      carbohydrates that occur during sprouting under field conditions. The bulbs were
      watered over a period of 23 days to simulate the onset of the rainy season. Even
      though there was no significant change of the total fructan content, the
      distribution and the composition of the fructan fraction within the different
      leaf scales of the bulbs altered during sprouting. The major changes occurred in
      the innermost scales, the total fructan content increased from 300 (day 0) to 607
      (day 23) g kg-1 dry mass and high-performance anion-exchange chromatography
      analysis revealed a significant increase of fructans with low degree of
      polymerization (DP). With respect to starch, the most pronounced difference
      accompanying the transition to growth was also in the innermost scales. In
      contrast to fructans, starch content decreased from 241 (day 0) to 60 (day 14) g
      kg-1 dry mass. These results demonstrate that starch, and not fructan, is used as
      the carbon and energy source for sprouting. The water content data suggest the
      involvement of fructans in water relations. The preferential accumulation of low
      DP fructans and sucrose within the innermost scales directs the water flow to
      where it is most needed for growth. Similar changes were obtained for bulbs in
      the dry soil, but transformation rates were much slower and occurred to a lesser
      extent, indicating that these reactions were not triggered but were accelerated
      by water.

PMID- 12060275
TI  - Changes in phenol content during strawberry (Fragariaxananassa, cv. Chandler)
      callus culture.
AB  - Total soluble phenols, soluble flavanols, (+)-catechin, ferulic acid and 1-O
      feruloyl-beta-d-glucose were analyzed during the development of a strawberry
      (Fragariaxananassa, cv. Chandler) callus culture. The time-course changes of the
      different phenols assayed were well correlated with callus growth and morphology.
      The changes in polyphenol oxidase (EC 1.10.3.1-2) and beta-glucosidase (EC
      3.2.1.21) activities in the callus were also examined. The total phenol, soluble
      flavanols and (+)-catechin contents were high during the preexponential and
      exponential phases of growth. The subsequent decrease in (+)-catechin
      concentration coincided with high levels of polyphenol oxidase activity. The 1-O
      feruloyl-beta-d-glucose content was highest as callus growth ceased, and its
      subsequent decrease was accompanied by the increased production of ferulic acid.
      This increase in ferulic acid was accompanied by an increase in beta-glucosidase
      activity. The ferulic acid content decreased at the end of culture, when callus
      growth had stopped and showed clear symptoms of senescence. This decrease in the
      ferulic acid concentration was accompanied by an increase in the levels of
      ferulic acid bound to cell wall components.

PMID- 12060276
TI  - Enhanced photochemical light utilization and decreased chilling-induced
      photoinhibition of photosystem II in cotton overexpressing genes encoding
      chloroplast-targeted antioxidant enzymes.
AB  - The aim of this study was to determine whether increases in stromal superoxide
      dismutase (SOD; EC 1.15.1.1), ascorbate peroxidase (APX; EC 1.11.1.11) and
      glutathione reductase (GR; EC 1.6.4.2) via transformation could reduce
      photosystem (PS) II photoinhibition at low temperature for cotton (Gossypium
      hirsutum L.) plants and to determine by what mechanism this protection may be
      realized. During 3-h exposures of lincomycin-treated leaf discs to 10 degrees C
      and a photon flux density of 500 &mgr;mol m-2 s-1, all transgenic plants
      exhibited significantly greater PSII activity and O2 evolution than did wild-type
      plants. Also, the rate constant of PSII photoinactivation was significantly lower
      for all transgenic plants than for wild-type plants. No significant differences
      existed between genotypes in non-photochemical quenching of chlorophyll a
      fluorescence and the regulated component of the thermal dissipation of excitation
      energy. The relationship between changes in variable to maximum chlorophyll
      fluorescence (Fv/Fm) and the time-dependent averaged excessive light exposure was
      similar for all genotypes. This observation excluded the possibility that
      differences in PSII photodamage were due to improvements in the direct protection
      of PSII from active oxygen by antioxidant enzyme overproduction. Similar
      decreases in Fv/Fm during the stress treatment for all genotypes when leaves were
      pre-treated with 3-(3',4'-dichlorophenyl)-1,1-dimethylurea (DCMU) suggested that
      the effect of overproduction involved events downstream of PSII in the electron
      transfer pathway. Since all transgenic plants exhibited a significantly higher
      photochemical quenching of chlorophyll fluorescence during the chilling
      treatment, we concluded that, under the conditions used in this study, the
      enhancement of the protection of PSII from photodamage by increasing the stromal
      antioxidant enzyme activity in cotton leaves was due to the maintenance of a
      higher rate of electron transport and, consequently, a lower reduction state of
      QA.

PMID- 12060277
TI  - Photoperiodic control of dormancy in Sedum telephium and some other herbaceous
      perennial plants.
AB  - The environmental control of dormancy and flowering of the herbaceous perennial
      Sedum telephium was studied in controlled environments. Short photoperiods
      induced growth cessation and the formation of resting buds in both seedlings and
      mature plants, whereas long photoperiods resulted in immediate growth activation
      of dormant buds. No chilling was required for dormancy release, even in plants
      induced to dormancy and maintained at high temperature (21 degrees C) for more
      than 3 months. The critical photoperiod for dormancy release was about 15 h, a
      minimum of four long-day (LD) cycles (24 h) being required. The true
      photoperiodic nature of this response was ascertained by night interruption
      experiments. Flowering of S. telephium was found to have an obligatory LD
      requirement, with no requirement for vernalization. The critical photoperiod and
      minimum number of inductive cycles for floral induction were the same as for
      dormancy release. Dormancy release by long days was also obtained in preliminary
      experiments with three other herbaceous perennials. The eco-physiological
      significance of photoperiodic control of dormancy is discussed, and it is
      concluded that the mechanism ensures stability of winter dormancy, even under
      conditions of climatic warming.

PMID- 12060278
TI  - Chilling-induced leaf abscission of Ixora coccinea plants. III. Enhancement by
      high light via increased oxidative processes.
AB  - The role of increased oxidation induced by successive stresses of chilling and
      high light in the induction of leaf abscission was studied in Ixora coccinea
      plants in relation to auxin metabolism and oxidative processes. Exposure of
      plants following dark chilling (7 degrees C for 3 days) to high light (500-700
      &mgr;mol m-2 s-1 photosynthetically active radiation) for 5 h at 20-25 degrees C
      enhanced chilling-induced leaf abscission. This abscission was inhibited by
      pretreatment with the antioxidant butylated hydroxyanisole, alpha
      naphthaleneacetic acid or the ethylene action inhibitor, 1-methylcyclopropene.
      The oxidative processes initiated during the low light period following the dark
      chilling period, such as indoleacetic acid (IAA) decarboxylation and lipid
      peroxidation, were further enhanced by subsequent exposure to high light.
      Photoinhibition, expressed by the reduction of the chlorophyll fluorescence
      parameter Fv/Fm, was evident following exposure to high light, irrespective of
      the temperature of the pretreatment, but this reduction persisted only in chilled
      plants. This suggests that oxidative processes generated during and after the
      chilling period might have inhibited the recovery from photoinhibition. The
      chilling stress under darkness induced a 60% reduction in superoxide dismutase
      (SOD) activity and significant increases (130-600%) in the activities of several
      other antioxidative enzymes. These data suggest that the chilling-induced
      reduction in SOD activity may well be responsible for the increase in the
      oxidative stress induced by the subsequent light treatment, as expressed by the
      increased enzymatic activities. Taken together, this study provides further
      support for the involvement of oxidative processes in the events occurring in
      tissues exposed to sequential chilling and light stresses, leading to reduction
      in free IAA content in the abscission zone and to leaf abscission.

PMID- 12060279
TI  - Boron compartmentation in roots of sunflower plants of different boron status: A
      study using the stable isotopes 10B and 11B adopting two independent approaches.
AB  - The intracellular compartmentation of boron (B) in roots of sunflower plants
      precultured with 100 &mgr;M B (high B) or 1 &mgr;M B (low B) was studied using
      two independent approaches. In the first approach, short-term efflux studies
      using the stable isotopes 11B and 10B were carried out. In roots of high B
      plants, the calculated concentrations of B (nmol gFW -1) were 52.6 in the cell
      wall, 7.5 in the vacuole, 27.1 in the cytosol and 48.0 in the free space. In
      roots of low B plants, the concentrations of B (nmol gFW -1) were 43.4 in the
      cell wall, 2.8 in the vacuole, 17.9 in the cytosol and almost zero in the free
      space. Although the B supply differed by a factor 100, the B concentrations in
      the cytosol and the vacuole of low B plants were 66 and 37% of the respective
      concentrations in high B plants. This suggests an additional role for B in plant
      metabolism, besides its function in the cell wall. In the second approach, root B
      pools (cell sap and water-insoluble residue) were determined for comparison, and
      found to be in good agreement with the results from the efflux study.

PMID- 12060280
TI  - A GC-MS method for determination of amino acid uptake by plants.
AB  - In this study, we present a rapid, robust and sensitive method for quantification
      of plant amino acid uptake using universally (U) (13C, 15N)-labelled amino acids
      and gas chromatography-mass spectrometry (GC-MS). Amino acids were analysed as
      their tert-butyldimethylsilyl (tBDMS) derivatives and displayed detection limits
      in the range 10-100 fmol on column, depending on the amino acid. The technique
      allows for simultaneous detection and quantification of both unlabelled and
      isotopically labelled species of amino acids. This makes simple quantification of
      plant amino acid uptake from an isotopically labelled source possible. The
      analytical variation was low, concerning total amino acid concentrations
      (relative standard deviation, rsd, less than 5.3%) as well as enrichment of U
      13C, 15N-labelled glycine (Gly), arginine (Arg) and glutamic acid (Glu)
      (rsd<2.1%). An application of the GC-MS method was conducted on non-mycorrhizal
      Pinus sylvestris roots supplied with U-13C, 15N-labelled amino acids. Intact,
      labelled amino acids were traced in root extracts. This provided conclusive
      evidence of plant root uptake of intact amino acids. Uptake rates of the three
      amino acids Gly, Glu and Arg in the range 0.5-37.9 &mgr;mol g-1 dry weight h-1
      were recorded. These rates are comparable with those recorded in earlier studies
      of amino acid uptake, using other methods, as well as uptake rates measured for
      nitrate and ammonium.

PMID- 12060281
TI  - Light activates H2 15O flow in rice: Detailed monitoring using a positron
      emitting tracer imaging system (PETIS).
AB  - Water (H2 15O) translocation from the roots to the top of rice plants (Oryza
      saliva L. cv. Nipponbare) was visualized over time by a positron-emitting tracer
      imaging system (PETIS). H2 15O flow was activated 8 min after plants were exposed
      to bright light (1 500 &mgr;mol m-2 s-1). When the light was subsequently
      removed, the flow gradually slowed and completely stopped after 12 min. In plants
      exposed to low light (500 &mgr;mol m-2 s-1), H2 15O flow was activated more
      slowly, and a higher translocation rate of H2 15O was observed in the same low
      light at the end of the next dark period. NaCl (80 mM) and methylmercury (1 mM)
      directly suppressed absorption of H2 15O by the roots, while methionine
      sulfoximine (1 mM), abscisic acid (10 &mgr;M) and carbonyl cyanide m
      chlorophenylhydrazone (10 mM) were transported to the leaves and enhanced
      stomatal closure, reducing H2 15O translocation.

PMID- 12060282
TI  - The inhibition of ammonium uptake in excised birch (Betula pendula) roots by
      batatasin-III.
AB  - In northern Sweden, plants growing in association with the clonal dwarf shrub
      Empetrum hermaphroditum usually exhibit limited growth and are N-depleted.
      Previous studies suggest that this negative effect by E. hermaphroditum may be
      explained, at least in part, by the release of phenolic compounds, particularly
      the dihydrostilbene, batatasin-III from foliage to soil. In the present work, we
      investigated whether batatasin-III has the potential to interfere with NH4+
      uptake in birch (Betula pendula) roots. Excised birch roots were exposed to
      batatasin-III during brief periods in 15NH4+ solutions, and then analyzed for
      labeled N. Batatasin-III inhibited N-NH4+ uptake by 28, 89 and 95% compared with
      the control, when roots were treated with 0.1, 1.0 and 2.8 mM of batatasin-III,
      respectively. The effect of 1.0-mM batatasin-III was greater at pH 4.2 than at pH
      6.8. In addition, the inhibition of N-NH4+ uptake by batatasin-III was not
      reversed after rinsing the roots in water and transferring them to a batatasin
      III free solution. Furthermore, birch seedlings immersed in a 1.0-mM batatasin
      III solution for 2 h, and then replanted in pots with soil, had decreased growth,
      such that 10 weeks after treatment, the dry mass of both shoots and roots was
      reduced by 74 and 73%, respectively, compared with control seedlings. This
      suggests that a brief exposure to batatasin-III may have a long-term inhibitory
      effect on whole plant growth. Using plasma membrane vesicles isolated from easily
      extractable spinach (Spinacia oleracea) leaves, it was found that batatasin-III
      strongly inhibited proton pumping in isolated plasma membrane vesicles, while it
      only slightly inhibited ATP hydrolytic activity. The uncoupling of proton pumping
      from ATP hydrolytic activity suggests that batatasin-III disturbs membrane
      integrity. This hypothesis was further supported by a greater efflux of ions from
      birch roots immersed in a batatasin-III solution than from roots in a control
      solution.

PMID- 12060283
TI  - Ascorbate transport from the apoplast to the symplast in intact leaves.
AB  - Infiltration of reduced ascorbate (ASC) into the leaves of Betula pendula Roth
      and subsequent measurement of its loss therein after incubation allowed us to
      follow ascorbate transport from apoplast to symplast in intact leaves. All of the
      ascorbate extracted from the native apoplast was in fully oxidized form,
      dehydroascorbate (DHA). When 5 mM of ASC was infiltrated into the leaves, its
      intense decay occurred, but only 55% of ASC lost was recovered in apoplast as
      DHA. When ASC was added to the freshly extracted intercellular washing fluid
      (IWF), ASC oxidation occurred as well. However, all oxidized ASC was recovered as
      DHA, indicating that further decomposition of DHA did not occur. Similarly, all
      of the ASC infiltrated into the leaves was found therein either as ASC or DHA
      after incubation of leaves for up to 60 min. On this base the ascorbate
      infiltrated into the leaves and not recovered in the IWF was interpreted as
      ascorbate taken up into the symplast. The calculated uptake rates of ascorbate at
      different ASC concentrations followed saturation kinetics with the maximum uptake
      rate of 300 nmol m-2 plasma membrane (PM) area min-1 and Michaelis constant of
      12.8 mM. The uptake of ascorbate was significantly inhibited by the addition of
      dithiothreitol or by PM H+ ATPase inhibitor erythrosin B. Thus, our results
      support the previous observations that DHA is preferably transported from the
      apoplastic to the cytoplasmic side of the membrane and show that this process is
      dependent upon PM proton gradient.

PMID- 12060284
TI  - Cloning and characterization of leaf senescence up-regulated genes in sweet
      potato.
AB  - Genes that are expressed during leaf senescence in sweet potato (Ipomoea batatas,
      cv. Tainong 57) were identified by the isolation of cDNA fragments with the mRNA
      differential display method. Eight senescence-associated cDNA clones for mRNAs
      differentially expressed during leaf senescence were obtained and characterized.
      Northern blot analysis indicated that all these clones represented genes that are
      up-regulated during natural leaf senescence. Among them, five cDNA clones have
      been obtained in full length by screening a senescing leaf cDNA library or by
      performing rapid amplification of cDNA ends. DNA and protein database searches
      revealed that clones SPA15 and SPC9 encode proteins of unknown function. The
      other six clones SPG31, SPC20, SPG27, SPC25, SPC15 and SPC1 showed significant
      sequence homology to known genes encoding a cysteine proteinase, isocitrate
      lyase, S-adenosylmethionine decarboxylase, cysteine proteinase inhibitor and
      metallothionein-like type I protein. The gene expression patterns represented by
      SPG31, SPG27 and SPA15 were found to be highly specific in senescing leaves. The
      corresponding transcripts for SPG31, SPG27 and SPA15 were below detectable levels
      in other organs such as flowers, stems, roots and tubers. The possible
      physiological roles of these gene products in the leaf senescence process are
      discussed.

PMID- 12060285
TI  - Molecular cloning and in situ hybridization of alpha-l-arabinofuranosidase from
      carrot cells.
AB  - The cDNA of extracellular alpha-l-arabinofuranosidase (alpha-l-AFase, EC
      3.2.1.55) secreted from suspension-cultured carrot cells (Daucus carota L. cv.
      Kintoki) was isolated and characterized. The nucleotide sequence of the cDNA (2.4
      kb) revealed an open reading frame consisting of 655 amino acid residues.
      Sequence homology research showed 28.4% identity to the alpha-l-AFase A protein
      of Aspergillus niger. The genomic DNA was cloned by PCR, and the nucleotide
      ligature sequence showed 18 exons and 17 introns. The first intron was upstream
      of the initiation codon. In situ hybridization revealed that the alpha-l-AFase
      gene is expressed in the root meristem, elongation zone and the root hair of
      carrot seedlings, indicating that this enzyme may participate in cell
      proliferation and development of carrot root cells.

PMID- 12060286
TI  - Overlapping expression of cytosolic glutamine synthetase and phenylalanine
      ammonia-lyase in immature leaf blades of rice.
AB  - In order to estimate whether cytosolic glutamine synthetase (GS1; EC 6.3.1.2) is
      partly coupled to the reaction of phenylalanine ammonia-lyase (PAL; EC 4.3.1.5)
      in developing organs of rice (Oryza sativa L.), we compared the expression
      pattern of transcripts and proteins for GS1 and PAL in the tissue sections from
      leaf blades at various stages of development. In immature vascular bundles of
      unexpanded leaf blades, GS1 mRNA was mainly detected in xylem parenchyma cells,
      mestome-sheath cells, and sclerenchyma cells. PAL transcripts were also
      accumulated in these cell types. Vascular bundles in midribs of immature leaf
      blades contained mRNAs and proteins for both GS1 and PAL abundantly in
      sclerenchyma cells, although distribution of these two proteins was not
      completely overlapped. In immature vascular bundles in midribs, lignin deposition
      was observed in cell walls of xylem parenchyma cells, mestome-sheath cells and
      sclerenchyma cells. These results implied that a part of GS1 in unexpanded leaf
      blades is possibly involved in reassimilation of ammonia released from PAL
      reaction during the lignin production.

PMID- 12060287
TI  - Differential leaf stress responses in young and senescent plants.
AB  - Responses to low temperature, mechanical wounding and salicylic acid (SA)
      treatments were studied in 3-week-old (young) and 6-week-old (senescent)
      Arabidopsis thaliana (L.) Heynh. plants by analyzing increases in Pal1 and Pr1
      expression and superoxide dismutase (SOD; EC 1.15.1.1) and peroxidase (POX; EC
      1.11.1.7) activities. Young plants showed higher Pal1 transcript accumulation
      after low temperature and wounding. In contrast, senescent plants presented
      higher accumulation of Pr1 transcripts after SA treatments. Similar results were
      obtained with the ethylene-insensitive etr1 mutant, suggesting that these
      differences are not related to increased ethylene content in senescent tissues.
      SOD activity and inducibility were lower, whereas POX activity and inducibility
      were higher in senescent plants. A possible relationship between senescence
      associated changes in responses to stress and in the metabolism of active oxygen
      species is discussed.

PMID- 12060288
TI  - Endogenous levels of polyamines in the organs of cucumber plant (Cucumis sativus)
      and factors affecting leaf polyamine contents.
AB  - Polyamine compositions of various organs from hydroponically cultivated cucumber
      plants (Cucumis sativus L. cv. Sharp-1) and factors affecting the leaf polyamine
      content were examined. Diamine putrescine was found most abundantly in the root,
      while a relatively large amount of spermine was detected in the reproductive
      organs such as the immature fruit and the calyx (+stamen). Spermidine was present
      at the highest level in rapidly growing tissues such as newly expanded leaf and
      fruit at an early developing stage, implying the possible involvement of
      spermidine in the growth and development of these young tissues. Polyamine
      content of cucumber leaves changed during the day. Especially, the putrescine
      content of upper leaves showed a striking decrease from the morning to the night.
      Alterations of leaf Ca or Mg content did not significantly affect leaf polyamine
      composition. On the other hand, abnormal cucumber leaves showed altered polyamine
      composition. Yellowing of the leaf intervein resulted in a striking decrease in
      spermidine content without a significant change in putrescine and spermine
      content. By contrast, the leaves infected with the phytopathogen, powdery mildew,
      showed decreased putrescine and increased spermine content in response to the
      degree of fungi infection. The possible usefulness of polyamines as a diagnostic
      marker of plant development and physiological disorder is discussed.

PMID- 12060289
TI  - The effect of AOA on ethylene and polyamine metabolism during early phases of
      somatic embryogenesis in Medicago sativa.
AB  - Changes in the levels of ethylene, 1-aminocyclopropane-1-carboxylic acid (ACC), 1
      (malonylamino)cyclopropane-1-carboxylic acid (MACC) and polyamines were
      simultaneously investigated during the early phases of alfalfa somatic
      embryogenesis. These included the period of induction and subculture of callus,
      and 3- and 7-day suspension cultures for the induction of somatic embryogenesis.
      The polyamines contained in the embryogenic callus were found to include
      putrescine (Put), spermidine (Spd) and spermine (Spm), but the level of Spm was
      much less than that of Put and Spd. There was a dramatic increase in MACC after
      induction of embryogenesis, and ACC levels were lower in somatic embryos than in
      embryogenic callus. Induction of embryogenesis for 3 days increased the levels of
      ACC and polyamines to a maximum level, and these then reduced as the
      embryogenesis proceeded. The ratios of Put/Spd and ACC/MACC were decreased during
      the induction. This indicated that both high levels of ACC and polyamines might
      be a prerequisite for early differentiation during the induction of the
      embryogenesis. Thus, there appears not to be competition between polyamine
      biosynthesis and ethylene biosynthesis at least during the induction of somatic
      embryogenesis, because both the polyamines and ACC were simultaneously increased
      during the induction period. Conversion of ACC into MACC and the maintenance of a
      relatively high level of polyamines, especially Spd, appear to be important for
      further development of the embryos. When aminooxylvinylglycine (AOA) was added at
      the initiation of the callus subculture, it had no significant effect on the
      callus growth, the ethylene production and ACC level of the callus. However, AOA
      increased the numbers of the embryos accompanying an increase in Spd level and S
      adenosylmethionine decarboxylase (SAMDC) activity. Thus, the AOA effect could be
      associated with Spd increase rather than with the effect of ethylene
      biosynthesis.

PMID- 12060290
TI  - Importance of the cytochrome pathway of mitochondrial electron transport over the
      alternative pathway during the Kok effect in leaf discs of pea (Pisum sativum).
AB  - The Kok effect refers to the progressive light-induced inhibition of dark
      respiration at low light intensities, which saturates around the light
      compensation point. This appears as a sudden break around the light compensation
      point in the plot of photosynthesis versus light intensity. The magnitude of the
      break can be considered as a measure of the Kok effect. In the present work, the
      importance of different components of dark respiration during the Kok effect was
      investigated by using low concentrations of mitochondrial inhibitors in leaf
      discs of pea (Pisum sativum L. cv. Azad P1). The effects of glucose (stimulates
      respiration) and 0.8 M sorbitol (imposes osmotic stress and inhibits
      photosynthesis) were also studied for comparison. The magnitude of the break
      decreased significantly in the presence of antimycin A or oligomycin (inhibitors
      of cytochrome pathway of mitochondrial electron transport and ATP synthase,
      respectively). In contrast, there was no significant change with
      salicylhydroxamic acid (SHAM; an inhibitor of alternative pathway of
      mitochondrial electron transport). The magnitude of the break increased
      significantly with glucose, and decreased on exposure to osmotic stress. Our
      results suggest that the Kok effect (inhibition of dark respiration in light) is
      modulated by inhibitors of cytochrome pathway and ATP synthesis, but not that of
      the alternative pathway.

PMID- 12060291
TI  - How phenology influences physiology in deciduous forest spring ephemerals.
AB  - Spring ephemerals of deciduous forest are adapted to take advantage of the high
      light period available in early spring. They appear shortly after snow melt and
      complete their aboveground growth, including fruit production, within 2 months.
      After they produce new buds, they senesce and enter dormancy. Dormancy is not
      very deep in spring ephemerals and during summer differentiation occurs in the
      bud of the apparently resting organ. Low soil temperatures release dormancy, and
      the shoots and roots then grow slowly over autumn and winter. The goal of this
      paper is to show how this characteristic phenology influences many aspects of
      spring ephemerals' physiology, and the influences these different physiological
      parameters have on each other. Spring ephemerals have high photosynthetic rates
      that allow them to rapidly accumulate carbohydrates and complete their
      aboveground growth in a few weeks. To sustain high photosynthetic rates in early
      spring, the plants must be able to absorb water efficiently at low soil
      temperatures and to allocate large amounts of nutrients to the shoot to
      compensate for lower enzymatic activity at low temperatures. Nutrients are mainly
      absorbed in spring, although the root system is established in autumn. This means
      that a large amount of both carbohydrates and nutrients is translocated from the
      perennial organ to the developing shoot starting in autumn through early spring.
      Spring ephemerals have low nutrient absorption rates, but high resorption
      efficiency during leaf senescence. Nevertheless, their high nutrient needs
      restrict them to rich forest soils. The annual growth rate of spring ephemerals
      is very slow and this is more likely related to the inherent slow growth rate of
      the perennial organ than to their short leaf life. As soon as carbohydrate
      reserves are replenished in spring, sink limitation apparently builds up and
      induces leaf senescence. A better understanding of the factors controlling the
      growth rate of spring ephemerals is needed before we can predict these plants'
      response to climatic changes.

PMID- 12060292
TI  - Role of glutathione in adaptation and signalling during chilling and cold
      acclimation in plants.
AB  - Glutathione is an important component of the ascorbate-glutathione cycle, which
      is involved in the regulation of hydrogen peroxide (H2O2) concentrations in
      plants. During chilling and cold acclimation, i.e. exposure to temperatures
      between 0 and 15 degrees C, H2O2 may accumulate. Excess electrons from the
      photosynthetic and respiratory electron transport chains can be used for the
      reduction of oxygen, thus producing superoxide radicals (O2.-); these are
      subsequently transformed to H2O2 via superoxide dismutase (SOD; EC 1.15.1.1).
      During the removal of excess H2O2, reduced glutathione (GSH) is converted to its
      oxidised form (GSSG), and GSH is regenerated by the activity of NADPH-dependent
      glutathione reductase (GR; EC 1.6.4.2). At low non-freezing temperatures, high
      GSH content and GR activity were detected in several plant species, indicating a
      possible contribution to chilling tolerance and cold acclimation. Changes in H2O2
      concentration and GSH/GSSG ratio alter the redox state of the cells and may
      activate special defence mechanisms through a redox signalling chain. The finding
      that several defence genes have antioxidant responsive elements or GSSG binding
      sites in their regulatory regions supports the idea that redox signalling is
      involved in regulating gene expression in response to low temperature.

PMID- 12060293
TI  - Control of plant development by limiting factors: A nutritional perspective.
AB  - It is postulated that limiting nutritional factors play a major role in the
      regulation of some aspects of plant development, and can provide an alternative
      to mechanisms based on the concept of hormonal control. This hypothesis is
      consistent with experimental evidence of the role of water as a limiting factor
      in (1) seed maturation and viviparous germination, (2) the elongation and
      phototropism of hypocotyls and coleoptiles, (3) the NO3--induced germination of
      dormant seeds, and (4) the release of buds from correlative inhibition. Studies
      on the influence of nutrition on morphogenesis have shown that the relative
      amounts of nitrogen and carbohydrate can determine the path of bud development as
      a shoot or rhizome. There is also evidence that either NO3- or sugar can limit
      lateral root initiation, and it is postulated that they may influence this
      process by a combination of osmotic and nutritional effects. The close
      correlation between environmentally induced developmental responses and the
      associated changes in the water or nutritional status of the responsive tissues,
      together with increasing evidence of the role of water and nutrients as
      transmitted signals and as regulators of gene expression, are in good agreement
      with their postulated role as limiting factors in the regulation of plant
      development.

PMID- 12060294
TI  - Molecular cloning of a Brassica napus thiohydroximate S-glucosyltransferase gene
      and its expression in Escherichia coli.
AB  - A genomic clone encoding a thiohydroximate S-glucosyltransferase (S-GT) was
      isolated from Brassica napus by library screening with probes generated by PCR
      using degenerated primers. Its corresponding cDNA was amplified by rapid
      amplification of cDNA ends (RACE) PCR and also cloned by cDNA library screening.
      The genomic clone was 5 896 bp long and contained a 173-bp intron. At least two
      copies of the S-GT gene were present in B. napus. The full-length cDNA clone was
      1.5 kb long and contained an open reading frame encoding a 51-kDa polypeptide.
      The deduced amino acid sequence shared a significant degree of homology with
      other glucosyltransferases characterized in other species, including a highly
      conserved motif within this family of enzymes corresponding to the glucose
      binding domain. The recombinant protein was expressed in Escherichia coli, and
      the enzyme activity was tested by a biochemical assay based on the measure of
      glucose incorporation. The high thiohydroximate S-GT activity detected from the
      recombinant protein confirmed that this clone was indeed a S-glucosyltransferase.

PMID- 12060295
TI  - Regulation of alternative oxidase activity during phosphate deficiency in bean
      roots (Phaseolus vulgaris).
AB  - Cyanide-resistant respiration was studied in mitochondria isolated from the roots
      of bean plants (Phaseolus vulgaris L. cv. Zlota Saxa) grown hydroponically up to
      16 days on a phosphate-sufficient (+P, control) or phosphate-deficient (-P)
      medium. Western blotting indicated that the alternative oxidase (AOX) was present
      only in its reduced (active) form, both in phosphate-sufficient and phosphate
      deficient roots, but in the latter, the amount of AOX protein was greater.
      Addition of pyruvate to the isolation, washing and reaction media made
      mitochondria from +P roots cyanide-insensitive, similar to mitochondria from -P
      roots. The doubled activity of NAD-malic enzyme (NAD-ME) in -P compared with +P
      root mitochondria may suggest increased pyruvate production in -P mitochondria.
      Lower cytochrome c oxidase (COX) activity and no uncoupler effect on respiration
      indicated limited cytochrome chain activity in -P mitochondria. In -P
      mitochondria, the oxygen uptake decreased and the level of Q reduction increased
      from 60 to 80%. With no pyruvate present (AOX not fully activated), inhibition of
      the cytochrome pathway resulted in an increased level of the ratio of reduced
      ubiquinone (Qr) to total ubiquinone (Qt) (Qr/Qt) in +P mitochondria, but did not
      change Qr/Qt in -P mitochondria. When pyruvate was present, the kinetics for AOX
      were similar in mitochondria from -P and +P roots. It is suggested that AOX
      participation in -P respiration may provide an acclimation to phosphate
      deficiency. Stabilization of the ubiquinone reduction level by AOX might prevent
      the harmful effect of an increased formation of reactive oxygen species.

PMID- 12060296
TI  - Characterisation and expression studies of a root cDNA encoding for ferredoxin
      nitrite reductase from Lotus japonicus.
AB  - A full-length cDNA encoding for ferredoxin-nitrite reductase (NiR, EC 1.7.7.1),
      has been isolated from a root cDNA library from the legume Lotus japonicus and
      characterised. The NiR gene (Nii) is present as a single copy in this plant, and
      encodes a protein of 582 amino acids. The Lotus NiR protein is synthesised as a
      precursor with an amino-terminal transit peptide consisting of 25 amino acid
      residues. Sequence comparisons with leaf NiRs from different plant species and
      with other related redox proteins identified in the root NiR the same highly
      conserved residues involved in the cofactor binding than previously reported for
      leaves. Besides, a putative binding site for ferredoxin was also found in the N
      terminal region of the protein. The NiR gene is expressed in roots and leaves,
      although the level of expression is much higher in roots, in accordance with the
      fact that L. japonicus assimilates nitrate mainly in roots. NiR mRNA, protein and
      activity are induced by nitrate in roots and leaves, while ammonium-grown plants
      only showed basal levels. No oscillations of NiR mRNA, protein and activity were
      observed during the day/night cycle, neither in roots nor leaves, making an
      interesting difference with rhythms observed in other plant species.

PMID- 12060297
TI  - Monophenolase activity of latent Terfezia claveryi tyrosinase: Characterization
      and histochemical localization.
AB  - The monophenolase activity of Terfezia claveryi tyrosinase (EC 1.14.18.1) is
      described for the first time. This enzyme is fully latent and can only be
      detected if SDS is present in the reaction medium. Monophenolase activity was
      localized within the ascocarp using histochemical techniques. A detailed kinetic
      study of the parameters affecting this activity has been carried out. Both the
      characteristic lag period and the steady-state rate are affected by pH and the
      enzyme and substrate concentrations. The presence of catalytic concentrations of
      o-diphenols affected the lag period but not the steady-state rate. By increasing
      the concentration of o-diphenols, it was possible to evaluate the enzyme
      activation constant, Kact, which showed a value of 7.2 &mgr;M. The experimental
      results are compatible with the mechanism previously described for tyrosinases
      from other sources.

PMID- 12060298
TI  - Purification and catalytic properties of polygalacturonase isoforms from ripe
      avocado (Persea americana) fruit mesocarp.
AB  - Endo-polygalacturonase (PG; EC 3.2.1.15) was recovered from the cell walls of
      avocado mesocarp (Persea americana Mill cv. Lula) tissue and purified by
      sequential ion exchange and gel permeation chromatography. Two isoforms (S-I and
      S-II) were recovered, exhibiting molecular masses of about 41 kD on size
      exclusion media and about 48 (S-I) and 46 (S-II) kDa as determined by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Both isoforms
      exhibited maximum activity at pH 6.0 against polygalacturonic acid (PGA) and
      hydrolyzed PGA of about 180 kDa to polymers of about 4 kDa. The catalytic
      activity of the 48-kDa isoform against PGA was slightly higher than that of the
      46-kDa isoform. The purified PGs catalyzed significant molecular mass downshifts
      in the polyuronides of pre-ripe avocados; however, the capacity of the enzymes to
      solubilize polyuronides from cell walls of pre-ripe fruit was limited.

PMID- 12060299
TI  - Tolerance to NaCl induces changes in plasma membrane lipid composition, fluidity
      and H+-ATPase activity of tomato calli.
AB  - Two tomato (Lycopersicon esculentum Mill. cv. Pera) callus lines tolerant to NaCl
      were obtained by successive subcultures of NaCl-sensitive calli in 50 and 100 mM
      NaCl-supplemented medium. Growth and ion content, as well as plasma membrane
      lipid composition, fluidity and H+-ATPase (EC 3.6.1.35) activity, were studied in
      both NaCl-sensitive and NaCl-tolerant calli. Although calli tolerant to 100 mM
      NaCl exhibited a reduced growth relative to calli sensitive to NaCl or tolerant
      to 50 mM NaCl, growth of calli tolerant to 100 mM NaCl was higher than that of
      NaCl-sensitive calli grown for one subculture in 100 mM NaCl. Growth in the
      presence of 100 mM NaCl provoked an increase of Na+ and Cl- content, but no
      significant changes in K+ and Ca2+. As compared with NaCl-sensitive and 50 mM
      NaCl-tolerant calli, plasma membrane vesicles isolated from calli tolerant to 100
      mM NaCl exhibited a higher phospholipid and sterol content as well as a lower
      phospholipid/free sterol ratio and a lower double bond index (DBI) of
      phospholipid fatty acids. The changes in plasma membrane lipid composition were
      correlated with a decrease of plasma membrane fluidity in calli tolerant to 100
      mM NaCl, as indicated by fluorimetric studies using diphenylhexatriene (DPH) as
      probe. Plasma membrane-enriched vesicles isolated from calli tolerant to 100 mM
      NaCl showed lower ATP hydrolysis and ATP-dependent H+-pumping activities, as well
      as a lower passive permeability to H+ than plasma membrane from NaCl-sensitive
      and 50 mM NaCl-tolerant calli. The involvement of the changes in plasma membrane
      lipid content and composition, fluidity and H+-ATPase activity in salt tolerance
      of tomato calli is discussed.

PMID- 12060300
TI  - Enhanced ATP-dependent copper efflux across the root cell plasma membrane in
      copper-tolerant Silene vulgaris.
AB  - We studied copper uptake in inside-out plasma membrane vesicles derived from
      roots of copper-sensitive, moderately copper-tolerant and highly copper-tolerant
      populations of Silene vulgaris (Amsterdam, Marsberg and Imsbach, respectively).
      Plasma membrane vesicles were isolated using the two-phase partitioning method
      and copper efflux was measured using direct filtration experiments. Vesicles
      derived from Imsbach plants accumulated two and three times more copper than
      those derived from Marsberg and Amsterdam plants, respectively. This accumulation
      was ATP-dependent. Also, 9-amino-6-chloro-2-methoxyacridine fluorescence
      quenching rates upon copper addition decreased in the order
      Imsbach>Marsberg>Amsterdam. Our results support the hypothesis that efflux of
      copper across the root plasma membrane plays a role in the copper tolerance
      mechanism in S. vulgaris.

PMID- 12060301
TI  - Effects of leaf wetting and high humidity on stomatal function in leafy cuttings
      and intact plants of Corylus maxima.
AB  - When rooted cuttings of Corylus maxima Mill. cv. Purpurea are moved from the wet
      and humid conditions of the rooting environment, the leaves frequently shrivel
      and die. Since the newly formed adventitious root system has been shown to be
      functional in supplying water to the shoot, stomatal behaviour in C. maxima was
      investigated in relation to the failure to prevent desiccation. Stomatal
      conductance (gs) in expanding leaves (L3) of cuttings increased almost 10-fold
      over the first 14 days in the rooting environment (fog), from 70 to 650 mmol m-2
      s-1. In contrast, gs of expanded leaves (L1) changed little and was in the region
      of 300 mmol m-2 s-1. Midday leaf water potential was much higher in cuttings than
      in leaves on the mother stock-plant (-0.5 versus -1.2 MPa) even before any roots
      were visible. Despite this, leaf expansion of L3 was inhibited by >50% in
      cuttings and stomata showed a gradual reduction in their ability to close in
      response to abscisic acid (ABA). To determine whether the loss of stomatal
      function in cuttings was due to severance or to unnaturally low vapour pressure
      deficit and wetting in fog, intact plants were placed alongside cuttings in the
      rooting environment. The intact plants displayed reductions in leaf expansion and
      in the ability of stomata to close in response to dark, desiccation and ABA.
      However, in cuttings, the additional effect of severance resulted in smaller
      leaves than in intact plants and more severe reduction in stomatal closure, which
      was associated with a 2.5-fold increase in stomatal density and distinctively
      rounded stomatal pores. The similarities between stomatal dysfunction in C.
      maxima and that observed in many species propagated in vitro are discussed, as is
      the possible mechanism of dysfunction.

PMID- 12060302
TI  - Cloning and characterization of cDNA of the GPI-anchored purple acid phosphatase
      and its root tissue distribution in Spirodela oligorrhiza.
AB  - A cDNA clone of the glycosylphosphatidylinositol (GPI)-anchored purple acid
      phosphatase (PAP) has been obtained by a combination of cDNA library screening
      and 5' rapid amplification of cDNA ends from Spirodela oligorrhiza plants grown
      under phosphate-deficient (-P) conditions. The open reading frame of the S.
      oligorrhiza PAP cDNA consists of 1 365 bp encoding a 455 amino acid protein. Its
      deduced amino acid sequence shows 82 and 80% similarity to Arabidopsis thaliana
      and Phaseolus vulgaris PAP, respectively. The amino acid residue, Ala439,
      followed by two more small amino acid residues, Asp and Ser, is predicted to be
      the GPI-anchoring (omega) site. The absence of a dibasic motif upstream of the
      putative omega site suggests that the PAP is a cell wall protein. This
      presumption is supported by the finding that PAP was released by digestion of the
      cell wall fraction with cellulase. The GPI anchor is speculated to be a signal
      for transporting PAP to the cell wall. Immunohistochemical results using -P plant
      roots demonstrate that PAP is preferentially distributed in the outermost
      cortical cells of roots but not in the epidermis, suggesting its role in
      acquiring inorganic phosphate under phosphate-deficient conditions. Northern blot
      analysis using the S. oligorrhiza PAP cDNA as a probe demonstrates that
      expression of the PAP gene increased during growth of -P plants and this time
      dependent occurrence in mRNA levels of the PAP in -P plants was also observed in
      their protein and activity levels.

PMID- 12060303
TI  - Physiological response of Pinus halepensis needles under ozone and water stress
      conditions.
AB  - The aim of this study was to evaluate how physiological processes of potted Pinus
      halepensis plants, grown under controlled conditions, were affected by ozone (O3)
      and/or water stress, integrating the gas exchange and biochemical data with
      fluorescence OJIP polyphasic transient data. Plants submitted to only water
      stress (T1) and with ozone (T3) showed a strong decrease in stomatal conductance
      and gas exchange, coinciding with a reduction of maximum yield of photochemistry
      (varphipo) and very negative values of leaf water potential. Simultaneously, a
      great increase of both PSII antenna size, indicated by absorption per reaction
      centre, and electron transport per reaction centre were found. The reduction of
      photosynthesis in the O3-treated plants (T2) by a slowing down of the Calvin
      cycle was supported by the increase of related fluorescence parameters such as
      relative variable fluorescence, heat de-excitation constant, energy de-excitation
      by spillover, and the decrease of varphipo. We suggest an antagonistic effect
      between the two stresses to explain the delayed ozone-induced decrease of
      stomatal conductance values for T3 with respect to T1 plants, by an alteration of
      the physiological mechanisms of stomatal opening, which involve the increase of
      intra-cellular free-calcium induced by ABA under co-occurring water shortage. We
      emphasise the importance of considering the intensity of the individual stress
      factor in studies concerning the interaction of stresses.

PMID- 12060304
TI  - Canopy development of a model herbaceous community exposed to elevated
      atmospheric CO2 and soil nutrients.
AB  - To test the prediction that elevated CO2 increases the maximum leaf area index
      (LAI) through a stimulation of photosynthesis, we exposed model herbaceous
      communities to two levels of CO2 crossed with two levels of soil fertility.
      Elevated CO2 stimulated the initial rate of canopy development and increased
      cumulative LAI integrated over the growth period, but it had no effect on the
      maximum LAI. In contrast to CO2, increased soil nutrient availability caused a
      substantial increase in maximum LAI. Elevated CO2 caused a slight increase in
      leaf area and nitrogen allocated to upper canopy layers and may have stimulated
      leaf turnover deep in the canopy. Gas exchange measurements of intact communities
      made near the time of maximum LAI indicated that soil nutrient availability, but
      not CO2 enrichment, caused a substantial stimulation of net ecosystem carbon
      exchange. These data do not support our prediction of a higher maximum LAI by
      elevated CO2 because the initial stimulation of LAI diminished by the end of the
      growth period. However, early in development, leaf area and carbon assimilation
      of communities may have been greatly enhanced. These results suggest that the
      rate of canopy development in annual communities may be accelerated with future
      increases in atmospheric CO2 but that maximum LAI is set by soil fertility.

PMID- 12060305
TI  - Characterization of an ethylene-induced esterase gene isolated from Citrus
      sinensis by competitive hybridization.
AB  - A simple new method, competitive hybridization, for identification of
      differentially regulated genes was used to isolate novel genes induced by
      ethylene in citrus (Citrus sinensis [L.] Osbeck cv. Shamouti) leaves. One of the
      isolated genes, an ethylene-induced esterase gene (EIE), was further
      characterized. The deduced protein sequence of this gene shows a similarity to
      those of several plant alpha/beta hydrolase gene family members, which are known
      to be involved in secondary metabolism. Northern blot analysis demonstrated that
      EIE mRNA was induced by ethylene within 4 h and accumulated to a very high level
      24 h after the initiation of ethylene treatment. Induction of EIE by ethylene
      could be counteracted by 1-methylcyclopropene, a potent ethylene perception
      inhibitor, indicating that the expression of EIE is ethylene-dependent. The
      bacterially expressed protein of EIE was recognized by antiserum against Pir7b, a
      naphthol AS esterase induced in rice by the non-host pathogen, Pseudomonas
      syringae pv. syringae. The EIE protein was identified in ethylene-treated leaves
      using anti-Pir7b antibodies. An alpha-naphthyl acetate esterase accumulated
      concomitantly with the increase in EIE protein in ethylene-treated citrus leaves.
      An enzyme activity assay followed by western analysis confirmed that the esterase
      was EIE.

PMID- 12060306
TI  - Caffeoyl-coenzyme A 3-O-methyltransferase enzyme activity, protein and transcript
      accumulation in flax (Linum usitatissimum) stem during development.
AB  - Flax (Linum usitatissimum) is a commercially important fiber crop in Europe.
      Lignification of its phloem fibers, although weak, causes a decrease in their
      commercial quality. In flax, fiber lignin mainly consists of guaiacyl (G) units
      in contrast to the mixed guaiacyl-syringyl (G-S) lignin type occurring in xylem
      fibers. G lignins are reported as more condensed polymers due to a higher
      frequency of 5-5 linkages, whereas the deposition of syringyl end groups in
      lignins increases the proportion of alky-aryl ether linkages as beta-O-4-bonds.
      The type of linkages within a lignin polymer depends on the methylation of either
      the 3-hydroxyl groups or both 3-OH and 5-OH groups, which is controlled by two
      enzymes: caffeate 3-O-methyltransferase (COMT) and caffeoyl-coenzyme A 3-O
      methyltransferase (CCoAOMT). First, we measured the in vitro activity of both
      OMTs in the flax stem tissues during stem development. CCoAOMT activity varied in
      the same way as COMT, i.e. increased gradually with stem maturity, from the top
      to the bottom of the stem, was maximum at the flowering stage and was lower, but
      still scorable, in the outer fiber-bearing tissues than in the xylem cells. In a
      second step, we focused our studies on the characterization of CCoAOMT in order
      to understand the implication of this enzyme in the lignification of flax fiber
      cells. CCoAOMT activity appeared to be associated with the accumulation of an
      acidic 33-kDa polypeptide identified as a CCoAOMT after immunological cross
      reactivity with a poplar CCoAOMT and microsequencing. The differential
      accumulation of the CCoAOMT protein was confirmed by immunolocalization on tissue
      prints and correlated with that of the transcripts, suggesting a transcriptional
      regulation of CCoAOMT in the flax stem.

PMID- 12060307
TI  - Hormone physiology of pea mutants prevented from flowering by mutations gi or
      veg1.
AB  - The veg1 (vegetative) mutant in pea (Pisum sativum L.) does not flower under any
      circumstances and gi (gigas) mutants remain vegetative under certain conditions.
      gi plants are deficient in production of floral stimulus, whereas veg1 plants
      lack a response to floral stimulus. During long days in particular, these non
      flowering mutant plants eventually enter a stable compact phase characterised by
      a large reduction in internode length, small leaves and growth of lateral shoots
      from the upper-stem (aerial) nodes. The first-order laterals in turn produce
      second-order laterals and so on in a reiterative pattern. The apical bud is
      reduced in size but continues active growth. Endogenous hormone measurements and
      gibberellin application studies with gi-1, gi-2 and veg1 plants indicate that a
      reduction in gibberellin and perhaps indole-3-acetic acid level may account, at
      least partially, for the compact aerial shoot phenotype. In the gi-1 mutant, the
      compact phenotype is rescued by transfer from a 24- to an 8-h photoperiod. We
      propose that in plants where flowering is prevented by a lack of floral stimulus
      or an inability to respond, the large reduction in photoperiod gene activity
      during long days may lead to a reduction in apical sink strength that is manifest
      in an altered hormone profile and weak apical dominance.

PMID- 12060309
TI  - 'Collateral damage' in perinatal warfare.

PMID- 12060310
TI  - Survey on maternal mortality in Swaziland using the sisterhood method.
AB  - Monitoring and evaluating maternal mortality in African countries is impossible
      without specific and reliable data and indicators. This study of maternal
      mortality using the 'Sisterhood Method' was undertaken in Swaziland. The crude
      data on 'sisterhood mortality' were obtained from the 1993-94 Multi-Purpose
      Household Survey carried out by the Central Statistics Office and Ministry of
      Health of Swaziland. A total fertility rate of 6.36, as given in the 1986
      Swaziland census, was used in estimating these indicators. Prior to this study,
      the maternal mortality rate (MMR) in Swaziland (based only on health facility
      data) was considered to lie within the range of 107-125 maternal deaths per 100
      000 live births. Use of the 'Sisterhood Method' allowed a more precise estimate
      of maternal mortality for the general population of Swaziland. The study revealed
      the estimated MMR to be 229 and the life-time risk of maternal death to be 1 in
      69. These values were most probably stable throughout the 6- to 7-year period
      before the survey.

PMID- 12060311
TI  - Epidemiological features of uterine rupture in West Africa (MOMA Study).
AB  - The aim of the study was (1) to assess the incidence of uterine rupture in West
      Africa; (2) to identify its risk factors there; (3) to assess their
      predictiveness. The study (MOMA study) was prospective and population based. Data
      on a large cohort of pregnant women were collected. Univariable and multivariable
      analysis was used including stepwise logistic regression. We identified 25 cases
      of clinically symptomatic uterine rupture in a population of 20 326 pregnant
      women giving an incidence rate of 1.2 uterine ruptures per 1000 deliveries. Five
      variables were significantly associated with uterine rupture (in both the
      univariable and multivariable analyses): uterine scars, malpresentation, limping,
      cephalopelvic disproportion and high parity (>or=7). In conclusion, the incidence
      of uterine rupture is high in West Africa, even in large cities where essential
      obstetric care is available and despite the low prevalence of uterine scars. A
      uterine scar multiplies the risk of uterine rupture by 11. Uterine rupture cannot
      be predicted from currently known risk factors, including uterine scars. The high
      case fatality rate (33.3%) and the associated perinatal mortality (52%) bear
      witness to the absence or inadequacy of health facilities in providing essential
      obstetric care and to the poor quality of maternal health care, even in major
      cities.

PMID- 12060312
TI  - Operative delivery during labour: trends and predictive factors.
AB  - Monitoring operative delivery trends provides the opportunity to consider whether
      changes are in a direction that will achieve the best outcomes for mothers and
      their infants. The aims of this study were to identify trends in and predictors
      of operative delivery (forceps, vacuum or caesarean) among women who have labour;
      and to determine trends in the operative methods used. The study was based on 616
      303 live, singleton, term births delivered between 1990 and 1997 in New South
      Wales, Australia. There was no change in the annual percentage of women who
      experienced labour and 20% had an operative birth during labour. The vacuum to
      forceps ratio declined from 1 : 6 in 1990 to 1 : 1 in 1997. Among women with
      labour, caesareans increased from 6.4% to 7.8%. For primiparae, the factors
      predictive of operative delivery (epidural analgesia, age > 34 years, induced or
      augmented labour and private care) did not change over time. A predictive model
      for multiparae did not have adequate fit, indicating the importance of data on
      prior birth history. Studies of trends in operative deliveries are most useful
      and consistent with decision making when interventions before the onset of labour
      and during labour are analysed separately. Furthermore, the vacuum:forceps ratio
      provides a useful tool for comparative analyses.

PMID- 12060313
TI  - Is the timing of exposure to infection a major determinant of acute lymphoblastic
      leukaemia in Hong Kong?
AB  - The hypothesis that protection of infants from exposure to infectious agents with
      delayed first exposure to one or more specific agents together contribute to the
      aetiology of childhood leukaemia, especially common acute lymphoblastic leukaemia
      (cALL), has substantial indirect support from descriptive epidemiology and case
      control studies in developed Western countries. A case-control study of childhood
      leukaemia diagnosed at ages 2-14 years has now been conducted in Hong Kong. Cases
      (n=98) formed a consecutive series of Chinese children diagnosed with acute
      leukaemia; controls (n=228) were identified following a survey using random digit
      dialling and required to attend for medical examination by a paediatrician.
      Interviews with mothers were conducted in hospital by one trained interviewer
      using a structured questionnaire. Odds ratios (OR) and 95% confidence intervals
      (CI) are reported for exposure variables capable of serving as proxies for
      exposure to infection in two critical time periods: first year of life, year
      before reference date (diagnosis for cases, corresponding date for controls).
      Analyses used logistic regression with adjustment for appropriate confounders.
      Change of area of residence reduced risk if during the first time period (OR =
      0.47 [95% CI 0.23, 0.98]) and increased risk if during the second (OR=3.92, [95%
      CI 1.47, 10.46]). Reported roseola and/or fever and rash in the first year of
      life reduced risk (OR=0.33 [95% CI 0.16, 0.68]) whereas tonsillitis in the period
      3-12 months before reference date increased risk (OR=2.56 [95% CI 1.22, 5.38]).
      Some other proxies for exposure to infection at the critical times were
      associated with predicted patterns of risk but day-care attendance failed to show
      predicted associations. These results provide support for the delayed exposure
      hypothesis in an affluent geographical setting in which population exposure to
      infectious agents is quite distinct from the settings of previous case-control
      studies.

PMID- 12060314
TI  - Analysis by gestational age of cerebral palsy in singleton births in north-east
      England 1970-94.
AB  - We report from a well-established cerebral palsy (CP) register the changes in CP
      rates by gestational age for singleton births over a 25-year period in north-east
      England. The gestational ages of numerators and denominators are of high accuracy
      back to 1970 because academic units in paediatrics and obstetrics were studying
      the assessment of gestational age in individual infants, and the distribution of
      gestational age across all births in the north-east from the 1960s. The rate of
      CP rose between 1970-75 and 1990-94 from 1.6 to 2.3 per 1000 singleton neonatal
      survivors, a rise of 0.7/1000 [95% CI 0.2, 1.3]. There was little change in the
      rate of CP in term infants whereas in preterm infants (<37 weeks) it rose from
      5.5 to 16.8, a rise of 11.3/1000 [95% CI 5.9, 16.8]. Rises occurred in the three
      preterm gestational age bands <28, 28-31, 32-36 weeks with the most marked rise
      in those <28 weeks from 0 to 112.7. The proportion of all cases of CP arising in
      the preterm group rose from 19% to 45%; and the proportion of the severest cases
      arising in the preterm group rose from 8% to 55%. In those born after 32 weeks,
      there is a preponderance of small-for-gestation infants, with 10% more than two
      standard deviations below the mean. All types of CP are more common in infants
      below average weight for gestation and this is most marked for the non-spastic
      types that are almost only seen in term, small-for-gestation infants. Gestational
      age is the crucial determinant of rate of CP and the increase in prevalence seen
      over the past 25 years is due to increased rates in preterm infants, not term
      infants. Both conclusions, suspected from birthweight analyses, are now
      demonstrated conclusively, with the contribution coming from those 32-36 weeks
      gestation as well as very preterm infants.

PMID- 12060315
TI  - The effect of the change in air temperature on the number of newborns in Vienna
      1984-99.
AB  - The number of daily births depends on a wide range of sociodemographic, temporal
      as well as many other mostly unknown factors, resulting in non-random patterns.
      We tested the hypothesis of the influence of the change in air temperature on the
      daily number of all newborns in Vienna (n=254 797) in the period 1984-99 (n=5843
      days). We found a significant association of sudden changes in temperature with
      the daily number of births. The observed effect is responsible for up to 0.27% of
      the explained variation in the regression model.

PMID- 12060316
TI  - Temporal distribution of distinct mast cell phenotypes during intestinal
      schistosomiasis in mice.
AB  - Mastocytosis is a common feature of helminth infection in most host species. We
      examined the temporal distribution and phenotype of mast cells during intestinal
      schistosomiasis in mice, using antibodies directed against histamine, a general
      mast cell marker, against mouse mast cell protease-1 (MMCP-1), a mucosal mast
      cell (MMC) marker, and against tryptase, a predominantly connective tissue mast
      cell (CTMC) marker. Ileal paraffin and/or cryosections of control, 8- and 15-week
      infected mice were quantitatively analysed. In the intestinal wall of non- and
      unisexual infected mice, a few dispersed mast cells were detected. In infected
      mice, a transient increase of mast cells in the mucosa and a gradual increase in
      the outer muscle layer were observed. MMCP-1 expressing MMCs were predominantly
      present in the mucosa during the acute phase [8 weeks postinfection (p.i.)],
      while tryptase and histamine immunoreactivity demonstrated that two subsets of
      CTMCs were predominantly present in the outer muscle layer at 15 weeks p.i.
      (chronic phase). In conclusion, these results reveal that, in mice, both MMCs and
      CTMCs are involved in the inflammatory response during schistosomiasis. The
      recruitment of each mast cell population is time-dependent and occurs at
      different locations. These data suggest that mastocytosis is associated with
      motility-related gastrointestinal symptoms and egg excretion.

PMID- 12060317
TI  - Polyspecific malaria antibodies present at the time of infection inhibit the
      development of immunity to malaria but antibodies specific for the malaria
      merozoite surface protein, MSP1, facilitate immunity.
AB  - Serum taken from mice immune to malaria as a result of infection and drug cure,
      or from mice immunized with a recombinant form of the merozoite surface protein,
      MSP1, can provide passive protection of recipient mice against the lethal
      parasite, Plasmodium yoelii YM. However, recipients of MSP1-immune serum go on to
      develop long-term immunity, whereas recipients of serum from mice naturally
      immune to malaria rapidly lose their resistance to infection. We demonstrate that
      'infection/cure' serum suppresses the development of both antibody and cell
      mediated parasite-specific responses in recipients, whereas these develop in
      recipients of MSP1-specific antibodies. These data have profound implications for
      our understanding of the development of malaria immunity in babies who passively
      acquire antibodies from their mothers.

PMID- 12060318
TI  - Gastro-allergic anisakiasis as a consequence of simultaneous primary and
      secondary immune response.
AB  - Gastro-allergic anisakiasis has been reported as an entity in which an acute
      parasitism by Anisakis simplex is accompanied by an immunoglobulin (Ig)E-mediated
      systemic allergic reaction. Serum samples were obtained from 24 patients within
      24 h after the onset of symptoms (day 0) and after 1 month (day 30) and in 13
      patients after 6 months. Total IgE was assessed by the Imx method. Specific IgE
      was assessed by CAP-FEIA. Specific IgM, IgG, IgG4 and IgA antibodies were
      assessed by enzyme-linked immunosorbent assay against crude extract (CE) and
      excretory-secretory products (ESP). IgE immunoblotting (IB) was directed against
      CE or ESP (day 0 and day 30). We found a rise of total IgE, specific IgE, number
      of bands in IgE-IB, IgG and IgG4 between day 0 and day 30 with a fall to near
      basal levels after 6 months. IgM levels were highest at day 0, falling over the
      next 6 months and IgA levels remained almost unchanged. Correlation studies
      revealed a parallel stimulation of nearly all Ig isotypes, except IgM anti-ESP,
      whose antibody levels correlated negatively with specific IgG levels. We found an
      extension of the IgE antibody repertoire in IB. We conclude that the allergic IgE
      mediated reaction in the course of gastro-allergic anisakiasis involves a
      parallel secondary Th2 type memory response and a primary immunologic stimulation
      of both Th2 and Th1 lymphocyte subsets against previously unrecognized antigens.

PMID- 12060319
TI  - Cystatins of filarial nematodes up-regulate the nitric oxide production of
      interferon-gamma-activated murine macrophages.
AB  - Cystatins of two filarial nematodes were studied with regard to their capacity to
      up-regulate the production of nitric oxide (NO) in vitro, and the effects were
      analysed. Recombinant cystatin of the human pathogenic filaria Onchocerca
      volvulus and of the rodent filaria Acanthocheilonema viteae significantly
      enhanced the NO production of interferon (IFN)-gamma-activated macrophages of
      BALB/c and C3H/HeJ mice. Truncated cystatins lacking the N-terminal protease
      inhibitory active site, and showing marginal protease inhibitory activity, up
      regulated the NO production to the same extent as the full-length proteins,
      indicating that the effect on the NO production is independent of cysteine
      protease inhibition. NO did not contribute to the suppression of proliferative T
      cell responses exerted by filarial cystatins, as shown in other studies, since NO
      synthase inhibitors did not restore proliferative responses. The up-regulation of
      NO production induced by filarial cystatins was partly dependent on the
      production of interleukin-10 and tumour necrosis factor-alpha, since depletion of
      both cytokines by antibodies led to a diminution of the enhanced NO production by
      22-48%. Our data suggest that filarial cystatins are potent triggers of the
      production of NO, a mediator which was shown to have a role as an effector
      molecule against filarial worms in vitro and in vivo.

PMID- 12060320
TI  - Vaccination of calves against Ostertagia ostertagi with cysteine proteinase
      enriched protein fractions.
AB  - Cysteine proteinase enriched fractions obtained by thiol-sepharose chromatography
      of Ostertagia ostertagi membrane-bound protein extract (S3-thiol) or total adult
      excretory-secretory (ES-thiol) products were tested in a vaccination experiment
      to evaluate their protective efficacy against O. ostertagi in cattle. Calves were
      vaccinated three times and subsequently challenged with a trickled infection of
      25,000 infective larvae in total over 25 days (1000 L3/day, 5 days/week).
      Geometric mean cumulative egg counts in the ES-thiol group were reduced by 60%
      during the 2-month period between the first challenge infection and necropsy,
      compared to the control group (P < 0.002). No reduction in egg output was
      observed in the S3-thiol group. At necropsy, calves immunized with ES-thiol had a
      significantly higher percentage of inhibited L4 larvae (9.8%) and had in total
      18% less worms than the control calves, but this reduction was not statistically
      significant. Both the female and male adult worms were significantly smaller in
      the ES-thiol group than in the control group. Although no significant difference
      was observed in the number of eggs per female worm between the groups, there was
      a trend to less eggs per female worm in the ES-thiol group. Number of worms, size
      of adult worms and number of eggs per female worm were not significantly
      different between the S3-thiol group and the control group. Systemic immunization
      with QuilA as adjuvant induced a significant rise in Ostertagia-specific antibody
      levels in the abomasal mucosa. Ostertagia-specific local antibody levels showed a
      significant negative correlation with the size of the adult worms, the number of
      eggs per female worm and the cumulative faecal egg counts. However, these
      correlations were quite weak and did not appear to be isotype-specific.

PMID- 12060321
TI  - Toxoplasma gondii infection can regulate the expression of tumour necrosis factor
      alpha receptors on human cells in vitro.
AB  - The in vitro regulation of tumour necrosis factor (TNF)-alpha receptors during
      Toxoplasma gondii infection of human MRC5 fibroblasts and human myelomonocytic
      THP-1 cells was investigated. Cells were infected with the virulent RH of T.
      gondii. TNFR membrane receptors were analysed by flow cytometry with biotinylated
      TNF-alpha. Shedding of the soluble form of TNFR1 and TNFR2 in cell culture
      supernatants was measured by enzyme-linked immunosorbent assay, and expression of
      mRNA production of TNFR1 and TNFR2 was analysed by quantitative real-time
      polymerase chain reaction, 1 h after infection. In the MRC5 cell line, T. gondii
      infection did not induce any up- or down-regulation of membrane TNFRs, soluble
      TNFRs or mRNA of TNFRs. However, THP-1 cell infection with living parasites
      induced a significant soluble TNFR1 release by THP-1 cells after 1 h. We detected
      an approximately 50% up-regulation (P < 0.01) of soluble TNFR1 in infected THP-1
      cells compared to controls. No change in soluble TNFR2 levels was observed in the
      same conditions. Moreover, infection decreased the level of TNF membrane
      receptors, but had no effect on TNFR1 and TNFR2 mRNA levels. TNFR modulation by
      T. gondii infection, in vitro, depends on the cell type. Furthermore, our data
      suggest that living parasites control the shedding of the soluble form of TNFR1.
      This mechanism may influence the role of TNF-alpha in toxoplasmosis.

PMID- 12060322
TI  - Ropivacaine: is it time for children?

PMID- 12060323
TI  - Epidermolysis bullosa in children: pathophysiology, anaesthesia and pain
      management.

PMID- 12060324
TI  - Surface mapping of peripheral nerves in children with a nerve stimulator.
AB  - Defining anatomical landmarks may be difficult in the growing child. With the aid
      of a peripheral nerve stimulator, the path of many superficial peripheral nerves
      can be 'mapped' prior to skin penetration by stimulating the motor component of
      the peripheral nerve percutaneously with a 2-3.5 mA output. The required current
      will vary and is dependent upon the depth of the nerve and the moistness of the
      overlying skin. This 'nerve mapping technique' has proved particularly useful for
      brachial plexus, axillary, ulna and median nerve blocks in the upper limb and
      femoral and popliteal nerve blocks in the lower limb. It is a useful teaching
      tool and improves the success rate of peripheral nerve blocks in children of all
      ages.

PMID- 12060325
TI  - Caudal block with 4 mg x kg-1 (1.6 ml x kg-1) of bupivacaine 0.25% in children
      undergoing surgical correction of congenital pyloric stenosis.
AB  - BACKGROUND: Since 1970, bupivacaine 0.25% in a dose of 4 mg x kg-1 (1.6 ml x kg
      1) has been used at the Hospital Infantil de Mexico for caudal block in children
      undergoing surgical correction of congenital pyloric stenosis (CPS). Although
      this dose is considered unsafe, in our experience, it has been associated with a
      high success rate and a low incidence of adverse events. This experience has not
      been previously documented. METHODS: A retrospective cohort of patients
      undergoing surgical correction of CPS was studied. Nineteen patients received
      general anaesthesia while 223 received caudal block. The latter were then grouped
      according to the sedation technique. The rate of successful caudal blocks and
      complications were considered the major outcomes of the study, whereas the
      postsurgical fasting period and hospital stay were considered secondary outcomes.
      RESULTS: The rate of success of caudal block was 96%. Anaesthetic complications
      related to bupivacaine were present in 1.3%. Mortality occurred in the
      postoperatory period in one septic patient who also was suffering from
      gastroschisis that required general anaesthesia. Postoperatory fasting period and
      hospital stay tended to be higher with general anaesthesia than caudal block.
      However, of the 19 patients receiving general anaesthesia, five suffered serious
      comorbidity and nine were failed caudal blocks. CONCLUSIONS: Caudal block with
      bupivacaine 0.25% (4 mg x kg-1) was associated with a low rate of anaesthetic
      complications. Further prospective studies to clarify the risks and benefits are
      required.

PMID- 12060327
TI  - The rotational technique with a partially inflated laryngeal mask airway improves
      the ease of insertion in children.
AB  - BACKGROUND: This study compared the ease of insertion of the laryngeal mask
      airway (LMA) with a partially inflated cuff using the standard 'nonrotational'
      technique versus the rotational technique. METHODS: One hundred and forty-five
      children undergoing anaesthesia using the LMA were randomly assigned to either
      method. The cuff was partially inflated in both groups. The ease of insertion was
      assessed by the time taken to complete the LMA insertion, the number of attempts
      before successful placement and the occurrence of complications. RESULTS: The
      success rate of insertion at the first attempt was higher in the rotational
      technique group (99% versus 79%, P < 0.05). All patients in the rotational group
      had the mask inserted within two attempts. On the other hand, three patients had
      the mask inserted on the first attempt with the rotational technique after three
      unsuccessful attempts by an anaesthesiologist with the standard 'nonrotational'
      technique. Insertion technique made no difference on insertion time. CONCLUSIONS:
      The rotational technique was associated with a higher success rate for insertion
      and a lower incidence of complications in children. Using the rotational
      technique with a partially inflated cuff could be the first-choice approach in
      paediatric patients.

PMID- 12060326
TI  - Airway management in spontaneously breathing anaesthetized children: comparison
      of the Laryngeal Mask Airway with the cuffed oropharyngeal airway.
AB  - BACKGROUND: The efficacy and safety of the smallest size of the cuffed
      oropharyngeal airway (COPA) for school age, spontaneously breathing children was
      investigated and compared with the Laryngeal Mask Airway (LMA). METHODS: Seventy
      children of school age (7-16 years) were divided into two groups: the COPA (n=35)
      and the LMA (n=35). Induction was with propofol i.v. or halothane, nitrous oxide,
      oxygen and fentanyl. After depression of laryngopharyngeal reflexes, a COPA size
      8 cm or an LMA was inserted. Ventilation was manually assisted until spontaneous
      breathing was established. For maintenance, propofol i.v. and fentanyl or
      halothane with nitrous oxide were used. Local anaesthesia or peripheral blocks
      were also used. RESULTS: Both extratracheal airways had a highly successful
      insertion rate, but more positional manoeuvres to achieve a satisfactory airway
      were required with the COPA, 28.6% versus LMA 2.9%. The need to change the method
      of airway management was higher (8.6%) in the COPA group. After induction, the
      need for assisted ventilation was higher in the LMA group 54.3% versus 20% in the
      COPA group. Airway reaction to cuff inflation was higher in the LMA group 14.3%
      versus COPA 5.7%. Problems during surgery were similar, except continuous chin
      support to establish an effective airway was more frequent (11.4%) in the COPA
      group. In the postoperative period, blood on the device and incidence of sore
      throat were detected less in the COPA group. CONCLUSIONS: The COPA is a good
      extratracheal airway that provides new possibilities for airway management in
      school age children with an adequate and well sealed airway, during spontaneous
      breathing or during short-term assisted manual ventilation.

PMID- 12060328
TI  - The size 1.5 laryngeal mask airway (LMA) in paediatric anaesthetic practice.
AB  - BACKGROUND: The recently introduced size 1.5 laryngeal mask airway (LMA) is
      specifically designed for use in children weighing 5-10 kg. METHODS: We
      prospectively evaluated its use in 68 patients, mean age 8.7 months, who were
      undergoing a variety of routine surgical procedures. RESULTS: The overall
      incidence of complications was high (42%) and was significantly more common in
      younger patients. Most of these related to poor positioning of the LMA, or airway
      problems such as obstruction or laryngospasm. Critical incidents occurred in
      seven patients, and all but one of these was related to the use of an LMA.
      CONCLUSIONS: The size 1.5 LMA is a useful addition to the range available,
      although the overall complication rate is considerable and is inversely related
      to the age of the child.

PMID- 12060329
TI  - Thoracic epidural catheters placed by the caudal route in infants: the importance
      of radiographic confirmation.
AB  - BACKGROUND: Cephalad advancement of epidural catheters to the thoracic region via
      the caudal route has been shown to be feasible in neonates and small infants.
      This has allowed many young infants to receive thoracic level epidural analgesia
      with dilute local anaesthetic solutions using the simpler caudal approach. Since
      radiographic confirmation of the catheter tip is routine at this institution, we
      wished to determine how often radiographic studies led to adjustment or
      replacement of the epidural catheter. METHODS: After institutional review board
      approval, we retrospectively reviewed the medical records of neonates and infants
      less than 6 months of age who had thoracic or lumbar epidural analgesia via the
      caudal route between August 1995 and January 2000. Demographic data were
      recorded, including age, weight and type of surgery. The epidural catheter type,
      tip location by radiograph and any manipulation of the catheter after the
      radiograph were also noted. RESULTS: During the study period, a total of 115
      infants were identified as having received caudal placement of a thoracic
      catheter. Radiographic studies were available for 86 of these infants. The
      position of 28 (32%) of the epidural catheters was considered to be inadequate
      after review of the confirmatory radiograph. Ten of these catheters were
      determined to be in the high thoracic or cervical region and were pulled back to
      the desired level. Seventeen of these catheters were coiled in the lumbosacral
      area and 15 of these were replaced at an adequate level. One catheter was found
      to be outside the epidural space in the presacral area. No correlation could be
      found between age, weight, type of catheter or type of surgery and the need for
      catheter manipulation. CONCLUSIONS: Even in young infants, radiographic
      determination of the catheter tip appears warranted when thoracic catheters are
      placed via the caudal route.

PMID- 12060330
TI  - Side-effects after inhalational anaesthesia for paediatric cerebral magnetic
      resonance imaging.
AB  - BACKGROUND: The aim of this study was to evaluate the type, incidence and
      duration of postprocedure side-effects in 168 children within the first 72 h
      after inhalational anaesthesia for magnetic resonance imaging (MRI). METHODS:
      Premedication and induction followed standardized routines. Maintenance of
      anaesthesia was performed with inhalational anaesthetics solely: isoflurane (n=60
      of 112; 53%), sevoflurane (n=32 of 112; 29%), desflurane (n=12 of 112; 11%) or
      halothane (n= 8 of 112; 7%) using a strapped on face mask (FiO2=0.4; flow 5 l.min
      1). When indicated, gadolinium was administered (n=45; OF 112; 40%). RESULTS: One
      hundred and twelve of 168 parents (67%) responded to questionnaires. In these 112
      children, pathological MR findings were found supratentorially (n=31; 28%),
      infratentorially (n=9; 8%), extracerebrally (n=12; 11%) or combined (n=9; 8%). In
      56 of these 112 children (50%), 14 different side-effects were reported. One hour
      after anaesthesia, 55 children suffered between one and four side-effects.
      Neurological side-effects were associated with age > or = 5 years (P < 0.01) or
      infratentorial pathophysiology (P < 0.01) and abdominal side-effects (P < 0.02),
      especially nausea (P < 0.001) with age > or = 5 years. CONCLUSIONS: Our findings
      indicate the need to inform parents of the incidence and variability of side
      effects after inhalational anaesthesia for minimally invasive, diagnostic
      procedures, such as MRI.

PMID- 12060331
TI  - The reliability of endtidal CO2 in spontaneously breathing children during
      anaesthesia with laryngeal mask airway, low flow, sevoflurane and caudal
      epidural.
AB  - BACKGROUND: Noninvasive devices for monitoring endtidal CO2 (PECO2) are in common
      use in paediatric anaesthesia. Questions have been raised concerning the
      reliability of these devices in spontaneous breathing children during surgery.
      Our anaesthetic technique for elective infraumbilical surgery consists of
      spontaneous breathing through a Laryngeal Mask Airway (LMA), low fresh gas flow,
      sevoflurane and a caudal epidural. We wanted to compare PECO2 and arterial CO2
      (PaCO2) during surgery. METHODS: Twenty children, aged 1-6 years, scheduled for
      infraumbilical surgery, were studied and one arterial sample was taken 45 min
      after induction of anaesthesia. PECO2, inspiratory PCO2, oxygen saturation, heart
      rate, respiratory rate, mean arterial blood pressure and expiratory sevoflurane
      concentration were measured every 5 min. The respiratory and circulatory
      parameters were stable during surgery. RESULTS: The mean PaCO2 - PECO2 difference
      was 0.15 (0.16) kPa [1.1 (1.2 mmHg)]. CONCLUSIONS: PECO2 is a good indicator of
      PaCO2 in our anaesthetic setting.

PMID- 12060332
TI  - Emergence behaviour in children: defining the incidence of excitement and
      agitation following anaesthesia.
AB  - BACKGROUND: Children display a variety of behaviour during anaesthetic recovery.
      The purpose of this study was to study the frequency and duration of emergence
      behaviour in children following anaesthesia and the factors that alter the
      incidence of various emergence behaviour following anaesthesia. METHODS: A
      prospective study of children who required outpatient lower abdominal surgery was
      designed to determine an incidence and duration of emergence agitation. We
      developed a 5-point scoring scale to study the postanaesthetic behaviour in these
      children. The scale included behaviour from asleep (score=1) to disorientation
      and severe restlessness (score=5). Children were scored by a blinded observer
      every 10 min during the first hour of recovery or until discharge from same day
      surgery. RESULTS: We found 27 of 260 children experienced a period of severe
      restlessness and disorientation (score 5) during anaesthesia emergence. Thirty
      percent of the children (79/260) experienced a period of inconsolable crying or
      severe restlessness (score 4 or 5) following anaesthesia. The frequency of this
      behaviour was greatest on arrival in the recovery room, but many children who
      arrived asleep in the recovery room later experienced a period of agitation or
      inconsolable crying. CONCLUSIONS: Repeated assessments of behaviour following
      anaesthetic recovery are required to define an incidence and duration of
      emergence agitation. Emergence agitation occurs most frequently in the initial 10
      min of recovery, but many children who arrive asleep experience agitation later
      during recovery.

PMID- 12060333
TI  - Evaluation of a new paediatric scavenging valve.
AB  - BACKGROUND: Prolonged exposure to anaesthetic gases may be associated with
      adverse effects. Scavenging is in widespread use in adult anaesthesia but it has
      been more difficult to find a satisfactory solution for use in paediatric
      anaesthesia. The Exeter Paediatric T-piece Scavenging (Exeter PTS) valve has been
      designed for use with a modified Jackson-Rees system to allow connection to an
      active or passive Approved Gas Scavenging System. METHODS: Use of the Exeter PTS
      valve was evaluated in 35 spontaneously breathing paediatric patients (mean age
      4.7 years, mean weight 16.7 kg) using each patient as their own control.
      Atmospheric pollution was measured using a Miran 1B infrared spectrophotometer.
      RESULTS: When using a modified Jackson-Rees breathing system with an open-ended
      bag, pollution levels of isoflurane exceeded the Occupational Exposure Standard
      of 50 p.p.m. When the Exeter PTS valve and an active scavenging system were used,
      pollution was significantly reduced to below 5% of the recommended limit.
      CONCLUSIONS: We conclude that there is a need to reduce atmospheric pollution
      when using a modified Jackson-Rees system in spontaneously breathing patients and
      that this can be achieved by use of the Exeter PTS valve.

PMID- 12060334
TI  - Enlargement of existing tracheostome using percutaneous dilators.
AB  - Children requiring long-term mechanical ventilation or with abnormalities of the
      upper airway may need a tracheostomy for prolonged periods of time. For these
      children, insertion of a larger tracheostomy tube may be required to match
      somatic growth. We describe a new method of enlarging the tracheal stoma in
      children, based on the existing technique of percutaneous dilational
      tracheostomy.

PMID- 12060336
TI  - Airway management in a baby with femoral hypoplasia-unusual facies syndrome.
AB  - We report the successful fibreoptic intubation through a laryngeal mask airway
      (LMA) while maintaining spontaneous respiration in an anaesthetized 3-month-old
      female infant with femoral hypoplasia-unusual facies syndrome, in whom direct
      laryngoscopy and intubation proved impossible.

PMID- 12060335
TI  - Reversible coma in children after improper baclofen pump insertion.
AB  - We report the occurrence of delayed postoperative coma in five of nine
      consecutive children following surgery for insertion of baclofen infusion pumps.
      We suspect that improper technique resulted in an inadvertent administration of
      an intrathecal baclofen bolus. We suggest ways to minimize this risk.

PMID- 12060338
TI  - How to manage the unavailability of an appropriately sized uncuffed tracheal
      tube?

PMID- 12060337
TI  - Tracheal rupture in a 12 year-old-child: a possible complication of tracheal
      intubation?

PMID- 12060339
TI  - The sitting or prone position for posterior fossa surgery?

PMID- 12060341
TI  - Use of the laryngeal mask airway in mucopolysaccharidoses.

PMID- 12060342
TI  - The neuropathology and pathogenesis of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease
      in which neuropsychiatric involvement occurs in about 50% of patients and carries
      a poor prognosis. Despite extensive research, the precise mechanisms of nervous
      tissue injury remain the least well understood. This article summarizes the
      important clinical neuropsychiatric features of SLE and, reviewing classical
      histopathological and more recent experimental studies, discusses theories
      concerning their presumed pathogenesis. The distinctive production of diverse
      autoantibodies seems to be related to defective clearance of apoptotic cells.
      Antibody-mediated neural cell injury and rheological disturbances represent the
      two principal suggested mechanisms of tissue injury. An interplay between these
      processes, underlying genetic factors, their modification by hormones,
      complicated by a number of secondary factors, may explain the wide spectrum of
      features encountered in this disease.

PMID- 12060343
TI  - Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene
      mutations. Study of aneural and innervated cultured myotubes.
AB  - Mutations in the sarcoglycan (SG) genes cause autosomal recessive muscular
      dystrophies. The absence of each SG complex component in muscle impairs the
      proper assembly of the entire SG complex, resulting in sarcolemmal damage. We
      investigated the consequences of beta-SG gene mutations in cultured muscle from
      two beta-SG mutated patients, and analysed each individual SG protein expression
      by cross-sectional immunocytochemistry and Western blot in aneural and innervated
      myotubes. Patients' muscle biopsy showed total loss of SG complex; however, a
      limited amount of beta-SG was detected in aneural and innervated myotubes, where
      the protein was localized to the plasma membrane. This paradoxical beta-SG
      expression can be attributable to antibody cross-reaction or to the expression of
      an unknown SG isoform specific of immature muscle. In our cultured myotubes, the
      other components of the SG complex were absent, suggesting that beta-SG gene
      mutations result in a defective assembly of the entire SG complex in early stages
      of muscle development, and that the role of beta-SG is crucial for the normal
      structure and/or function of the SG complex in the sarcolemma.

PMID- 12060344
TI  - Features of proliferation and in vitro drug resistance in central primitive neuro
      ectodermal tumours.
AB  - The features of proliferation in brain tumours are related with clinical
      prognosis for several types of brain tumours, especially gliomas. For childhood
      central primitive neuro-ectodermal tumours (cPNET), including medulloblastoma,
      this relation has previously been unclear. The aim of this study is to
      investigate the relationship between proliferative features of cPNET and in vitro
      resistance for cytostatic drugs measured with the 3-4,5-dimethylthiazol-2-yl-2,5
      diphenyltetrazolium-bromide (MTT) assay. Tumour material was obtained from 23
      surgical specimens of cPNET. The expression of the proliferation markers Ki-67,
      proliferating cell nuclear antigen (PCNA) and cyclin D1 was determined with
      immunohistochemistry, while S-phase and DNA ploidy were analysed by
      flowcytometric analysis cell scan (FACS). The in vitro resistance for 10
      cytostatic drugs was determined with the MTT assay. Drug resistance levels were
      available in 19 (83%) of the 23 samples with a complete profile of 10 cytostatic
      drugs tested in 14 samples. An excellent correlation in drug resistance scores
      was found between pharmacologically related drugs. The Ki-67 staining in 20
      samples varied from 10 to 60% and from 30 to 100% for PCNA. Cyclin D1 staining
      was negative in 11 out of 18 samples. The S-phase in 16 samples ranged from 2 to
      16%. Increased staining of Ki-67 was related with actinomycin D sensitivity (r 
      .603; P=0.022), while cells with a higher S-phase percentage were more resistant
      to ifosfamide (r.952; P<0.0001). In vitro drug resistance testing of central
      primitive neuro-ectodermal tumours (PNET) is feasible with the MTT assay.
      Ifosfamide resistance was related with increased Ki-67 and S-phase percentage of
      the tumour cells, while increased Ki-67 was also related with actinomycin D
      sensitivity. These findings suggest a cell cycle dependent activity of cytostatic
      drugs in vitro.

PMID- 12060345
TI  - Expression of hypoxia-inducible factor 1alpha in tumours of patients with
      glioblastoma.
AB  - Angiogenesis is a prominent feature of glioblastomas but the mechanisms involved
      in the control of this process are poorly understood. We have investigated the
      potential role of a recently described transcription factor, hypoxia-inducible
      factor 1 (HIF-1), which initiates the transcription of a number of hypoxia
      inducible genes, including those encoding vascular endothelial growth factor and
      its receptors. HIF-1 protein expression was assessed by immunocytochemistry,
      using a monoclonal antibody to the alpha subunit (HIF-1alpha). HIF-1 mRNA
      expression was assessed by reverse transcriptase-polymerase chain reaction (RT
      PCR) and the ribonuclease protection assay (RPA). Strong nuclear expression of
      HIF-1alpha protein was seen in the majority of glioblastomas and anaplastic
      astrocytomas, particularly surrounding areas of necrosis in glioblastomas. In the
      majority of these tumours upregulation of HIF-1alpha mRNA was also demonstrated,
      with a significant increase in glioblastomas compared to lower grade tumours. No
      correlation was found between the presence of HIF-1alpha protein and
      immunohistochemical expression of p53 protein. These findings are in keeping with
      an important role of HIF-1alpha in the vascularization of glioblastomas and
      suggest that upregulation is at least partly at a transcriptional level.

PMID- 12060346
TI  - Synapse loss is greater in presenile than senile onset Alzheimer disease:
      implications for the cognitive reserve hypothesis.
AB  - In the past, 'Alzheimer disease' (AD) referred to pathologic AD with clinical
      onset of dementia in the presenium, while 'senile dementia of the Alzheimer type'
      (SDAT) referred to senile onset AD. Because AD appears clinically homogeneous
      regardless of age of onset, the two subtypes in more recent years have not been
      distinguished. Pathologic differences have been noted, but synapse loss has not
      previously been compared between the two groups. Hypothesizing that synapse loss
      would be greater in presenile onset than senile onset AD, we compared synapse
      loss, as well as Alzheimer pathology in presenile and senile onset AD, using an
      ELISA method to quantify synaptophysin. Synaptophysin was significantly lower in
      presenile than senile AD in right frontal and bilateral parietal lobes. Neuritic
      plaque counts were significantly higher in presenile than senile AD in bilateral
      frontal and parietal lobes. Semi-quantitative evaluation of neurofibrillary
      tangles revealed significantly more tangles in bilateral frontal and parietal
      lobes in presenile than senile AD. Brain weight was significantly lower in
      presenile than senile AD. The differences in synapse loss and Alzheimer-type
      pathology in presenile and senile onset AD support the hypothesis that 'cognitive
      reserve' protects the human brain from neurodegenerative disease.

PMID- 12060347
TI  - Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease:
      possible role in tangle formation.
AB  - Neurofibrillary tangles (NFTs) and neuritic plaques (NPs) are two major
      histopathological lesions in Alzheimer's disease (AD). Although their
      aetiological relationship is unclear, both NFTs and dystrophic neurites of NPs
      display immunoreactivity for ubiquitin. This suggests that dysfunction in
      ubiquitin-mediated proteolysis and the resulting accumulation of ubiquitin
      conjugated proteins may contribute to the origination of dystrophic neurites and
      NFTs. We recently discovered a novel constituent of neuropathological protein
      aggregates, ubiquitin-binding protein p62, with evidence that the accumulation of
      ubiquitin-conjugated proteins and p62 into cytoplasmic inclusions might be
      interconnected. In the present work we examined in detail the role of p62 in AD
      type pathology, i.e. NFTs, NPs and neuropil threads. Using immunohistochemistry
      for p62, ubiquitin and hyperphosphorylated tau, we analysed parietal cortical
      samples of 15 clinicopathologically verified AD cases and nine nondemented aged
      subjects with abundant NPs. We found that p62 immunoreactivity appears early
      during neurofibrillary pathogenesis and is invariably and stably present in NFTs.
      In contrast, p62 was absent or barely detectable in neuropil threads.
      Furthermore, NP-associated dystrophic neurites were generally devoid of p62,
      regardless of their content of hyperphosphorylated tau and/or ubiquitin. The
      results suggest that early involvement of p62 might be critical in the
      aggregation of hyperphosphorylated tau into perikaryal aggregates, i.e. NFTs.

PMID- 12060348
TI  - Apoptosis of astrocytes with enhanced lysosomal activity and oligodendrocytes in
      white matter lesions in Alzheimer's disease.
AB  - Cerebral white matter lesions in Alzheimer's disease (AD) consist of subcortical
      degeneration and ischaemic-hypoxic changes. Glial changes are intimately
      associated with the white matter lesions, and regressive changes in astrocytes
      and loss of oligodendroglial cells have been reported. We quantitatively compared
      glial changes including apoptosis and enhanced lysosomal activity in the frontal
      and temporal white matter by using terminal dUTP nick end labelling (TUNEL) and
      immunohistochemistry for glial markers, lysosomes and apoptosis-regulating
      proteins in non-familial AD brains. The degree of myelin pallor and axonal loss
      varied considerably in both the frontal and temporal white matter but fibrillary
      gliosis in demyelinated lesions tended to be less prominent in the temporal white
      matter in AD cases. A morphometric study with planimetric methods for cross
      sectional areas of frontal and temporal white matter revealed that the white
      matter of AD cases manifested atrophy with significant reduction in frontal
      (11.9%) and temporal (29.4%) white matter compared to normal controls. Double
      immunolabelling for glial fibrillary acidic protein (GFAP) and KP1 (CD68)
      revealed KP1-positive fragmented structures within the weakly GFAP-labelled
      astrocytes. These KP1-positive structures correspond to process fragmentation and
      cytoplasmic vacuoles, which in turn indicate enhanced lysosomal activity during
      regressive changes in astrocytes. The KP1-modified astrocytes were not found in
      Pick's disease and corticobasal degeneration. The density of apoptotic glial
      cells, largely oligodendroglial, was significantly higher in the temporal than in
      the frontal white matter, and most GFAP-positive astrocytes with regressive
      changes were apoptotic. GFAP-positive astrocyte density was statistically the
      same in the frontal and temporal white matter, but the density of KP1-modified
      astrocytes was higher in the temporal than in the frontal white matter. The rate
      of white matter shrinkage was significantly correlated with the density of
      apoptotic glial cells and the density of KP1-modified astrocytes in the temporal
      lobe in AD cases. An increase in apoptotic glial cell density was found to
      contribute to GFAP-positive astrocytes with regressive changes in temporal white
      matter, while apoptosis of vascular smooth muscle cells did not show
      topographical accentuation. Astrocytes labelled with beta amyloid protein were
      not apoptotic, and the density of apoptotic cells labelled with CD95 and caspase
      3 was too low in both types of white matter to be statistically evaluated. Our
      results imply that regressive changes in astrocytes and glial apoptosis are, to
      some extent, associated with white matter lesions, particularly of the temporal
      lobe in AD brains. The presence of apoptotic astrocytes with evidence of
      regressive change could therefore be a histological hallmark for white matter
      degeneration in AD.

PMID- 12060349
TI  - Mixed pituitary gangliocytoma/adenoma (prolactinoma) with histogenetic
      implications.

PMID- 12060367
TI  - Mental health care in Brazil.

PMID- 12060368
TI  - Formal observations and engagement: a discussion paper.
AB  - Formal observation of patients at risk is extremely common in acute psychiatric
      facilities. Effectively a form of physical containment, observation is resource
      intensive, makes significant personal demands upon staff and skews the focus of
      nursing care towards the small group of patients judged to be most at risk. For
      patients, the experience of being observed is often less than therapeutic and, in
      some cases, counter productive. In this paper, the authors draw upon a variety of
      perspectives, including that of a psychiatrist and a service user. It is argued
      that the practice of formal observation is ineffective and may actually
      contribute to the poor state of UK acute psychiatric inpatient units, in terms of
      direct patient care, clinical decision-making and appropriate risk management. In
      a recent 'commentary' within this journal, the authors offered 'engagement' as an
      alternative to observation. In this paper, the meaning of engagement is refined
      and presented as a process of emotional and psychological containment of
      distress. The paper concludes that inappropriate over-use of formal observation
      as a custodial and defensive practice can contribute to a sense of dehumanization
      and isolation within acute psychiatric patients; engagement may provide a genuine
      (i.e. not just linguistic) alternative.

PMID- 12060369
TI  - Assertive community treatment: development of the team, selection of clients, and
      impact on length of hospital stay.
AB  - Mental health services have been criticized for the lack of focus and response to
      people suffering from a serious mental illness (SMI). Assertive community
      treatment (ACT) offers the potential for greater partnership working between the
      user and provider of mental health services. The author describes one approach in
      developing ACT in the UK. Four criteria were developed to identify the most
      appropriate service users for ACT: those with SMI, illness instability, illness
      disability and risk to self or others. Fifty-five clients were identified using
      these criteria and tracked for their length of hospital stay and frequency of
      admission 2 years before acceptance to an ACT team and for 12 months after.
      Duration of hospital stay was unchanged although both the frequency and total
      numbers of bed days were reduced.

PMID- 12060370
TI  - Judgement days: developing an evaluation for an innovative nursing model.
AB  - This paper reports on the process and outcomes of the evaluation of an innovative
      nursing model (the Tidal Model). In relation to process, the study has been used
      to refine the methodology in terms of defining important variables to take as
      outcome measures to be analysed both descriptively and inferentially. In relation
      to outcomes, the pre-post-test design has generated significant findings in
      relation to improved patient care.

PMID- 12060371
TI  - From compliance to concordance: a review of the literature on interventions to
      enhance compliance with antipsychotic medication.
AB  - Non-compliance with antipsychotic medication is observed in around 50% of people
      with schizophrenia and is a major preventable cause of psychiatric morbidity. A
      number of factors influence patient's decisions about taking medication and
      include awareness of illness, beliefs about treatment and side-effects of
      medication. A variety of interventions targeted at improving compliance have been
      tested. Education increases patients' understanding of their illness and
      treatment but does not improve compliance. However, interventions, such as
      compliance therapy, based on cognitive-behavioural techniques appear to be
      effective in enhancing compliance and preventing relapse.

PMID- 12060372
TI  - The aphasic person's views of the encounter with other people: a grounded theory
      analysis.
AB  - Being affected by aphasia influences the total life experience. The aim of this
      study was to generate a theoretical model, from a nursing perspective, of what
      aphasic persons (n = 12) experience in encounters with other people. Data were
      collected through interviews which adopted a biophysical, socio-cultural and
      psychological approach and then analysed using grounded theory method. Two main
      categories emerged, namely: 'interaction' and 'support'. Encountered experiences
      led to: 'a feeling of having ability'; 'a feeling of being an outsider'; and 'a
      feeling of dejection or uncertainty'. The feeling state was dependent on whether
      the interaction was 'obstructed' or 'secure' and on whether the support resulted
      in 'strengthened' or 'impaired' self-esteem. Therefore nurses need to give
      support that enhances patients' self-esteem and which results in them gaining a
      positive and realistic view of their aphasia, as well as involving those around
      them in this perspective. This then will give the possibility for the patient to
      turn the interaction process from an obstructed into a secure one.

PMID- 12060373
TI  - UK and USA Clinical Mental Health Nurse Specialists' perceptions of their work.
AB  - There is little scholarship to compare the work of mental health nurses in
      different countries, although this is perhaps understandable given that mental
      health nursing as a discrete discipline exists only in a few countries worldwide.
      The small-scale study reported here sought to compare the perceptions of UK and
      American Clinical Nurse Specialists of various aspects of their work, including
      latest professional developments, current therapies and interventions, and the
      major problems confronting nurses today. Prior to the main study being
      undertaken, a short questionnaire was piloted in both countries. The main
      questionnaire was distributed to 34 American nurses and completed by 25 (75.5%
      response rate), and to 28 UK nurses and completed by 24 (86% response rate).
      Descriptive statistics and content analyses were used to analyse the data which
      suggested that where UK nurses were concerned with the range and availability of
      services for clients and their families, American nurses were primarily
      preoccupied with the quality of those services. The American sample placed
      greater emphasis on the provision of care that enabled clients to take
      responsibility for themselves than did their UK counterparts. While acknowledging
      the limitations of the study, the results would appear to suggest that American
      nurses tend to favour humanistic care, have a belief in the efficacy of
      chemotherapy and aim to get people functioning independently. They fear the
      threat to their relationship with clients that managed care might entail.
      Concurrently, UK nurses appear to be preoccupied with finding appropriate
      services for their clients and they appear to believe that the changing nature of
      their work is designed to accommodate structural changes in the health service,
      rather than to meet the needs of clients. The implications of these findings are
      discussed.

PMID- 12060374
TI  - Counselling and mental health nursing: a qualitative study.
AB  - The author draws upon his experience of training, practising and teaching both
      counselling and mental health nursing in order to examine the relevance of
      counselling skills training to mental health nurses. The qualitative study
      reported in this paper elicits the feelings and thoughts of five mental health
      nurses about their attitude towards individual counselling work with mental
      health clients. It is asserted that newly qualified mental health nurses may feel
      inadequately prepared for this aspect of their work and they may also feel
      inadequately supported. Additional counselling training may help equip mental
      health nurses for the skills they need to work within the therapeutic
      relationship. By not providing adequate counselling skills training, mental
      health nurse educators may contribute to a cycle of incompetence. Training
      methods are identified that may enhance nurse training and help promote
      competence and confidence for the newly qualified nurse.

PMID- 12060375
TI  - Involving mental health service users and carers in curriculum development:
      moving beyond 'classroom' involvement.
AB  - Recent policy statements that address the future priorities for nurse education
      have emphasized that service users and carers should be actively engaged in
      partnerships with education professionals in all aspects of the curriculum. The
      development of this agenda is well advanced; however, examples of 'how to do it'
      are sparse. The development of a strategy to involve users and carers in the
      design and delivery of the Diploma of Higher Education in Nursing at Napier
      University provided an opportunity to evaluate the process of developing
      partnerships in this area of nurse education. This paper presents the findings
      from a process evaluation from the various standpoints of the key interest
      groups. The overall project and evaluation is outlined, along with methodological
      and practical issues surrounding this type of 'collaborative' evaluation. The
      importance and satisfaction of practical aspects of the project are examined. The
      issues of representativeness, expertise in 'involvement' and the importance of
      the 'process' of involvement are explored. Finally, the challenges to developing
      'meaningful involvement' that goes beyond 'classroom involvement' in nurse
      education are identified and discussed.

PMID- 12060376
TI  - Improving serious mental illness through interprofessional education.
AB  - Current health policies emphasize partnership between professional groups,
      between agencies and with users, to ensure more integrated health and social care
      services. However, a number of reasons have been consistently identified as
      inhibiting interprofessional working. Among the many factors identified are poor
      communication, conflicting power relations and role confusion, and these present
      immense challenges to those who wish to offer interprofessional education and
      training opportunities. East Gloucestershire NHS Trust worked in partnership with
      the University of Gloucestershire (formerly the Cheltenham and Gloucester College
      of Higher Education) to overcome these problems and deliver an important
      postqualifying interprofessional training for those working with people with
      serious mental illness - the Thorn-based 'Diploma in Integrated Approaches to
      Serious Mental Illness'. This collaborative initiative represents a good model by
      which practitioners of all disciplines can be trained to a high standard and meet
      the requirements of the National Service Framework for Mental Health. This paper
      describes the initiative and identifies the extent to which the course has, by
      mirroring the practice it is seeking to generate, 'pulled together' to ensure
      interprofessional, intersectoral and professional/user collaboration. The key
      challenges associated with interprofessional working (with people with serious
      mental illness and with others) and with course implementation and how these were
      met are discussed and further opportunities are identified.

PMID- 12060378
TI  - Temporary confusion: a fearful experience.
AB  - Older people admitted to hospital often develop acute temporary confusion.
      Earlier studies have focused on problems in providing care to the confused,
      causes of the confusion and the key aspects of caring. The aims of this study
      were to describe, from a nursing perspective, how older people experienced the
      phenomenon of temporary confusion and to describe the older peoples' reasoning
      when they described their experiences. Interviews with five older informants who
      had recovered from their confusional state were conducted and analysed using the
      phenomenological method. Two phenomena were studied, 'being temporarily confused'
      and 'reasoning about experiences of temporary confusion', each was found to be
      represented by four inter-related constituents. The phenomena can be understood
      as aspects of suffering and power imbalance between staff and older people.

PMID- 12060377
TI  - An evaluation of staff and patient views of and strategies employed to manage
      inpatient aggression and violence on one mental health unit: a pluralistic
      design.
AB  - Following an initial springboard study, a further more extensive piece of
      research was conducted to identify and evaluate approaches used to manage patient
      aggression and violence on three acute mental health wards. Data were gathered
      using an incident form, a questionnaire and interviews. The views of patients (n
      = 80), nurses (n = 72) and medical staff (n = 10) were explored. Findings
      revealed a clear distinction between the way staff and patients view both the
      problem and the response. Patients' view present staff approaches as
      'controlling' and believe that environmental and poor communication factors
      underpin aggressive behaviour. Staff, conversely, attribute aggressive behaviour
      to internal patient and external factors, which may explain the reason for
      approaches used. A strong correlation was found between type of patient
      aggression and response (r = 0.36, P < 0.000) and a high percentage of incidents
      reported were of an aggressive, as opposed to violent, nature. For example 70% of
      incidents involved verbal abuse or threat. Despite this, 47% (n = 103) of
      approaches incorporated the use of medication, restraint or seclusion. These are
      commonly referred to as traditional methods. Patients clearly view this
      controlling style as a part of the problem and an emphasis upon control and
      symptom reduction may be inappropriate given the type of aggression encountered.
      Key issues were further analysed using an internal, external and situational
      model, each of which endeavour to explain reasons for patient aggression from
      different perspectives. It is this emphasis upon sole perspectives that may both
      contribute to and result in the use of a limited number of management approaches
      adopted in practice. The integration of all three models to examine the complex
      nature of patient aggression and violence from a variety of perspectives may be
      the way forward. As a result, approaches to deal with this problem could be more
      meaningful and subsequently effective.

PMID- 12060379
TI  - The practice of early recognition and early intervention to prevent psychotic
      relapse in patients with schizophrenia: an exploratory study. Part 1.
AB  - In this article we describe the findings of an exploratory study into the
      application of early recognition and early intervention methods aimed at
      prevention of psychotic relapses in patients with schizophrenia. We addressed
      several models of symptom recognition plans and indicated how patients,
      healthcare professionals and other persons involved may be able to list and
      evaluate early warning signs systematically. We also paid attention to the role
      of the patient's family and to the potential effects of using early recognition
      and early intervention methods. In a follow-up article (part 2), we will focus
      more specifically on factors which favourably or adversely affect the use of
      early recognition and early intervention methods. The results of this exploratory
      study will be used to design an intervention protocol for nursing staff to serve
      as a tool for preparing symptoms recognition plans with the individual patient
      and his/her social network.

PMID- 12060380
TI  - The practice of early recognition and early intervention to prevent psychotic
      relapse in patients with schizophrenia: an exploratory study. Part 2.
AB  - In this article we describe the findings of an exploratory study into the
      application of early recognition and early intervention methods aimed at
      prevention of psychotic relapses in patients with schizophrenia. Following the
      results we described in part 1, we now focus specifically on factors which
      favourably or adversely affect the use of early recognition and early
      intervention methods. The following issues will be addressed: (i) information and
      education; (ii) attitude of health care professionals; (iii) the patient's
      insight; (iv) acceptance of illness; (v) motivation; (vi) other relevant patient
      characteristics; and (vii) continuity of care. Finally, the implications of the
      findings for the development of a nursing intervention protocol will be
      discussed.

PMID- 12060381
TI  - The beguiling effects of nurse-prescribing in mental health nursing: re-examining
      the debate.

PMID- 12060383
TI  - Passing the torch.

PMID- 12060384
TI  - The role of chemokines in melanoma tumor growth and metastasis.
AB  - Chemokines represent a large family of polypeptide signaling molecules that are
      notable for their role in chemotaxis, leukocyte homing, directional migration,
      and G protein coupled receptor activation. Chemo kines have recently been
      implicated in tumor progression and metastasis. The demonstration of chemokine
      expression and receptor activation in melanoma tumor cells themselves, and the
      tumor infiltrating leukocytes, may have important implications in terms of tumor
      progression and tumor cell homing to metastatic sites. In addition to their
      chemotactic and cell homing properties, chemokines and their receptors also play
      a part in other biologic functions relevant to oncogenesis, including cell
      proliferation, protease induction, tumor growth, and angiogenesis. Melanomas, and
      the cells derived from them, have been found to express a number of chemokines,
      including CXCL8 (interleukin-8), CXCL1-3 (MGSA-GROalpha-gamma), CCL5 (RANTES),
      and CCL2 (monocyte chemotactic protein-1), which have been implicated in tumor
      growth and progression. Furthermore, recent studies have demonstrated organ
      specific patterns of melanoma metastasis that correlate with their expression of
      specific chemokine receptors, including CXCR4, CCR7, and CCR10. This review will
      focus on the current biology of chemokines and chemokine receptors in the context
      of understanding their potential roles in melanoma progression and metastasis,
      and is not meant to be a comprehensive review of chemokine biology. Continued
      understanding and progress in the determination of the role of chemokines and
      their receptors in tumorigenesis and metastasis, including melanoma, may lead to
      novel approaches in the treatment and management of this disease.

PMID- 12060385
TI  - Drug resistance towards etoposide and cisplatin in human melanoma cells is
      associated with drug-dependent apoptosis deficiency.
AB  - Anticancer drugs kill susceptible cells through induction of apoptosis.
      Alterations of apoptotic pathways in drug-resistant tumor cells leading to
      apoptosis deficiency might represent a potent mechanism conferring drug
      resistance. We have assessed the effect of etoposide and cisplatin on the
      apoptotic pathways of the drug-sensitive human melanoma cell line MeWo as well as
      its etoposide- and cisplatin-resistant sublines (MeWo(Eto01), MeWo(Eto1), (and)
      MeWoCis01, MeWo(Cis1)). Etoposide and cisplatin induced apoptosis in drug
      sensitive MeWo cells as indicated by dose-dependent (i) cytochrome c release,
      (ii) caspase activation, (iii) DNA fragmentation, and (iv) cleavage of poly(ADP
      ribose)polymerase. In contrast, whereas low etoposide-resistant cells
      (MeWo(Eto01)) demonstrated reduced but detectable apoptotic activities, highly
      etoposide-resistant cells (MeWo(Eto1)) did not exhibit any of the apoptotic
      events observed in etoposide-induced cell death downstream of a strongly reduced
      cytochrome c release. Highly cisplatin-resistant cells (MeWo(Cis1)), however,
      demonstrated a reduced caspase 9 activity and cytochrome c release but the extent
      of effector caspase activation as well as DNA fragmentation was comparable to
      that of sensitive MeWo cells at equitoxic concentrations. In addition, poly(ADP
      ribose)polymerase cleavage was strongly reduced in highly cisplatin-resistant
      sublines. Taken together, sensitive and drug-resistant MeWo cells utilized
      different apoptotic pathways upon drug exposure in a drug-dependent fashion and
      apoptosis deficiency was strongly associated with the drug-resistant phenotype.

PMID- 12060386
TI  - Rab27b association with melanosomes: dominant negative mutants disrupt
      melanosomal movement.
AB  - The movement of melanosomes from post-Golgi compartments to the periphery of
      melanocytes is known to be regulated by factors including myosin Va and at least
      one Rab protein, Rab27a. Mutations in the genes encoding either protein in the
      mouse result in a hypopigmented phenotype mimicking the human disease Griscelli
      syndrome. Rab27b and Rab27a share 72% identity and they belong to the same
      melanocyte/platelet subfamily of Rab proteins. Rab27a orchestrates the transport
      of melanosomes by recruitment of the actin motor, myosin Va, onto melanosomes. By
      contrast, the function of Rab27b has remained elusive. In this study, we found
      that Rab27b mRNA is present in melanocytes and demonstrated the intrinsic GTPase
      activity of Rab27b protein. We explored the function of Rab27b by overexpression
      of two dominant negative mutants as well as the wild-type Rab27b in melan-a
      melanocytes. Green-fluorescent-protein-tagged Rab27b colocalizes with the
      melanosome marker tyrosinase-related protein 1 and with myosin Va at the cell
      periphery, whereas Rab27b mutants do not decorate melanosomes, and melanosomes in
      these mutant transfected cells redistribute from cell periphery to the
      perinuclear region. Furthermore, transient overexpression of the dominant
      negative forms of Rab27b caused diminution in both numbers and length of
      dendrites of melan-a cells. Our results suggest that Rab27b may regulate the
      outward movement of melanosomes and the formation or maintenance of dendritic
      extensions in melanocytes.

PMID- 12060387
TI  - Inactivation of tumor suppressor genes p15(INK4b) and p16(INK4a) in primary
      cutaneous B cell lymphoma.
AB  - Primary cutaneous B cell lymphomas represent a distinct group of
      lymphoproliferative disorders that can be distinguished from systemic lymphoma by
      their good response to local treatment and favorable prognosis. In systemic B
      cell lymphoma, inactivation of p15(INK4b) and p16(INK4a) is frequently observed
      and may be associated with a poor prognosis. There have been no comprehensive
      studies in primary cutaneous B cell lymphomas, however. Mechanisms of p15/p16
      inactivation include loss of heterozygosity, homozygous deletion, promotor region
      hypermethylation, and point mutation. We analyzed DNA from 36 cases of primary
      cutaneous B cell lymphomas, four systemic B cell lymphomas, and six benign B cell
      lymphoproliferative infiltrates for abnormalities of p15 and p16 using
      microsatellite markers for 9p21, methylation specific polymerase chain reaction,
      and polymerase chain reaction/single stranded conformational polymorphism
      analysis with exon specific primers. Expression of both p15 and p16 protein was
      assessed by immunohistochemistry. Loss of heterozygosity at 9p21 was identified
      in 2 out of 36 primary cutaneous B cell lymphomas. Hypermethylation of p15 and
      p16 promotor regions was identified in 8 of 35 (23%) and 15 of 35 (43%) cases,
      respectively. In two cases p16 hypermethylation was identified in recurrent
      disease but not in the initial tumor. No point mutations were identified. In
      seven patients, however, a polymorphism was observed in exon 3 of the p16 gene.
      In primary cutaneous B cell lymphomas with allelic loss or promotor
      hypermethylation of either p15 or p16, loss of expression in tumor cells was
      identified in 5 of 8 and 9 of 10 cases, respectively. Our findings suggest that
      p15(INK4b) and p16(INK4a) biallelic gene abnormalities are common in primary
      cutaneous B cell lymphomas, most frequently as a result of promotor
      hypermethylation. The presence of abnormalities in recurrent disease in some
      cases suggests that inactivation of p15 and p16 may be involved in disease
      progression.

PMID- 12060388
TI  - Infrequent Fas mutations but no Bax or p53 mutations in early mycosis fungoides:
      a possible mechanism for the accumulation of malignant T lymphocytes in the skin.
AB  - Mycosis fungoides (MF) is the most frequent manifestation of cutaneous T cell
      lymphoma but its cause and pathophysiology remain unclear. Because progression of
      lesions is characteristically slow, we hypothesized that mycosis fungoides
      originates from an accumulation of lymphocytes due to defective apoptosis of skin
      homing T lymphocytes. In this study, we investigate possible alterations of three
      molecules regulating apoptosis, i.e., Fas antigen, Bax, and p53, at the genomic
      level in skin lesions from 44 patients with MF, as Fas mediates one of two major
      pathways for apoptosis of activated T cells. Fas mutations were found in six
      patients using a polymerase chain reaction and single-strand conformational
      polymorphism method followed by cloning and sequencing of abnormal polymerase
      chain reaction products. The mutations predict for defective transmission of the
      death signal in three cases. Immunohistochemistry demonstrated the lack of Fas
      protein expression on dermal lymphocytes in one case with Fas gene mutation
      predicting for a truncated death domain, whereas Fas protein was expressed by
      dermal lymphocytes in the other investigated cases. By contrast, no mutations of
      Bax or p53 were found, whereas immunohistochemistry demonstrated increased p53
      expression in the nucleus of basal keratinocytes above the neoplastic infiltrate
      in some MF cases. These results support the hypothesis that Fas defects may play
      a role in the pathogenesis of MF.

PMID- 12060389
TI  - T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a
      particular type of cutaneous granulomatous inflammation.
AB  - Granuloma annulare is a common granulomatous infiltration of the skin of unknown
      etiopathogenesis. We analyzed granuloma annulare biopsies in 11 patients and
      could find in all patients significant numbers of CD4-T cells. These cells showed
      a broad usage of the different T cell receptor Vbeta families and a rather
      unbiased repertoire when the complementary determining region 3 spectra were
      analyzed by the Immunoscope technique. Comparison with the peripheral blood
      mononuclear cell repertoire, however, identified in all patients few skin
      specific expansions, which were for one patient also present in two distinct skin
      sites. Extensive sequence analysis of the complementary determining region 3
      region confirmed the presence of a limited number of skin-specific expansions
      together with various nonspecific T cell infiltrations. Analysis of the
      intralesional cytokine expression revealed abundant production of interleukin-2,
      which was not dominant in granulomas from leprosy patients and was not reflected
      by the cytokine profile in peripheral blood mononuclear cells. These results
      demonstrate the capacity of the granulomatous response to recruit T cells in high
      numbers with only few clones expanding specifically. The high local production of
      interleukin-2 might thereby play an important role in the nonspecific attraction
      of T cells to the granulomatous site.

PMID- 12060390
TI  - The majority of keratinocytes incorporate intradermally injected plasmid DNA
      regardless of size but only a small proportion of cells can express the gene
      product.
AB  - The expression of intradermally injected DNA by keratinocytes is found mainly in
      the upper and middle layers of the epidermis. To investigate the mechanism of
      this selective expression, we observed the sequential changes in the distribution
      of interleukin-6-expressing keratinocytes after the introduction of the
      interleukin-6 gene. Transgene expression first occurred in basal keratinocytes
      and subsequently expanded to all epidermal layers and then remained in the upper
      layers. Semiquantitative analysis indicated that keratinocytes in the lower
      layers incorporated and lost DNA earlier than those in the upper layers. In order
      to examine the effect of the DNA size on the transgene expression, we constructed
      a plasmid containing a full-length 9 kb cDNA of type VII collagen and introduced
      it into keratinocytes. The expression pattern of type VII collagen in the
      epidermis was the same as those for smaller genes. This suggests that plasmid
      size has little or no effect on the expression pattern of the transfected gene.
      To trace the introduced plasmid, we intradermally injected a green fluorescence
      protein expression plasmid coupled with a rhodamine flag. Almost all
      keratinocytes in the injected areas showed rhodamine fluorescence. Furthermore,
      some cells also expressed green fluorescence protein. A lack of rhodamine
      fluorescence in the nucleus suggested an impairment of plasmid DNA transport from
      the cytoplasm to the nucleus. Collectively, our results show that the majority of
      keratinocytes take up the intradermally injected DNA regardless of its size, but
      that the transfer of DNA from the cytoplasm to the nucleus is limiting the
      transgene expression.

PMID- 12060391
TI  - Relationship of neurologic degeneration to genotype in three xeroderma
      pigmentosum group G patients.
AB  - We studied three newly diagnosed xeroderma pigmentosum complementation group G
      patients with markedly different clinical features. An Israeli-Palestinian girl
      (XP96TA) had severe abnormalities suggestive of the xeroderma
      pigmentosum/Cockayne syndrome complex including sun sensitivity, neurologic and
      developmental impairment, and death by age 6 y. A Caucasian girl (XP82DC) also
      had severe sun sensitivity with neurologic and developmental impairment and died
      at 5.8 y. In contrast, a mildly affected 14-y-old Caucasian female (XP65BE) had
      sun sensitivity but no neurologic abnormalities. XP96TA, XP82DC, and XP65BE
      fibroblasts showed marked reductions in post-ultraviolet cell survival and DNA
      repair but these were higher in XP65BE than in XP82DC. XP96TA fibroblasts had
      very low XPG mRNA expression levels whereas XP65BE fibroblasts had nearly normal
      levels. Host cell reactivation of an ultraviolet-treated reporter assigned all
      three fibroblast strains to the rare xeroderma pigmentosum complementation group
      G (only 10 other patients previously reported). XP96TA and XP82DC cells had
      mutations in both XPG alleles that are predicted to result in severely truncated
      proteins including stop codons and two base frameshifts. The mild XP65BE patient
      had an early stop codon mutation in the paternal allele. The XP65BE maternal
      allele had a single base missense mutation (G2817A, Ala874Thr) that showed
      residual ability to complement xeroderma pigmentosum complementation group G
      cells. These observations agree with earlier studies demonstrating that XPG
      mutations, which are predicted to lead to severely truncated proteins in both
      alleles, were associated with severe xeroderma pigmentosum/Cockayne syndrome
      neurologic symptoms. Retaining residual functional activity in one allele was
      associated with mild clinical features without neurologic abnormalities.

PMID- 12060392
TI  - Transient CD44 variant isoform expression and reduction in CD4(+)/CD25(+)
      regulatory T cells in C3H/HeJ mice with alopecia areata.
AB  - Alopecia areata, an autoimmune disease affecting anagen stage hair follicles, can
      be induced by grafting spontaneous alopecia areata affected skin to normal-haired
      C3H/HeJ mice. As the onset of alopecia areata can be significantly retarded by
      anti-CD44 variant isoform 10 treatment, it was interesting to explore the
      underlying disease mechanism. Two weeks after transplanting alopecia areata
      affected skin, expression of CD44 variant isoforms 3, 6, 7, and 10 was strikingly
      upregulated as compared with sham-grafted mice. By 6 wk after grafting, CD44
      variant isoform levels had returned to normal, whereas in draining lymph nodes,
      CD44 variant isoform expression was slightly decreased. Leukocytes in the skin of
      mice with chronic alopecia areata expressed a hematopoietic isoform of CD44 and
      CD44 variant isoform 6 at an elevated level, but CD44 variant isoform 3
      expression was reduced. Cytokine expression in leukocytes of chronic alopecia
      areata affected skin was higher than in normal-haired controls. Cytokine
      expression also increased postsurgery in sham and alopecia areata grafted mice,
      but remained elevated only in mice receiving alopecia areata affected skin.
      Finally, from the skin of mice with chronic alopecia areata and of mice
      transplanted with alopecia areata affected skin, an increased number of CD4(+)
      and CD8(+) cells, but a strongly decreased number of CD4(+)/CD25(+) regulatory T
      cells was recovered. Thus, expression of CD44 variant isoforms is important for
      the migration of leukocytes during the initial period of alopecia areata. CD44,
      however, is apparently not involved in the maintenance of the disease state,
      which is characterized by high cytokine expression levels, an increased number of
      CD4(+) and CD8+ cells, but a low level of CD4(+)/CD25(+) suppressor cells.

PMID- 12060393
TI  - Involvement of transforming growth factor-beta2 in catagen induction during the
      human hair cycle.
AB  - The involvement of transforming growth factor-beta isoforms in the induction of
      the regressing phase (catagen) of human hair follicles were examined in vivo. In
      the growing phase (anagen), transforming growth factor-beta1 was detected at the
      hair cuticle and connective tissue sheath. Transforming growth factor-beta2 was
      restricted to the outermost cell layer of the outer root sheath. Transforming
      growth factor-beta3 was observed in the precortical hair matrix of anagen hair
      follicles. During the anagen-catagen transition phase, strong transforming growth
      factor-beta2 immunoreactivity appeared in the lower bulb matrix cells adjacent to
      the dermal papilla. In addition, transforming growth factor-beta2 and
      transforming growth factor-beta type II receptor were colocalized in the
      regressing epithelial strands, where terminal deoxynucleotidyl transferase
      mediated deoxyuridine triphosphate nick end-labeling-positive apoptotic cells
      were also found. Transforming growth factor-beta1 and transforming growth factor
      beta3 were mostly negative in the strand. Using an organ culture system, we
      investigated whether transforming growth factor-beta2 and its antagonists
      affected the transition process. Elongation of hair was significantly suppressed
      by transforming growth factor-beta2. Next, a neutralizing antibody and fetuin, a
      potent transforming growth factor-beta antagonist was tested. In the presence of
      the antibody as well as fetuin, hair follicles were markedly elongated in a
      concentration-dependent manner. These results strongly suggest that transforming
      growth factor-beta2 plays an essential part in the induction of the catagen phase
      of the human hair cycle.

PMID- 12060394
TI  - Rapid compensation for glycosylphosphatidylinositol anchor deficient
      keratinocytes after birth: visualization of glycosylphosphatidylinositol-anchored
      proteins in situ.
AB  - Pig-a, an X-linked gene, is a key component of glycosylphosphatidylinositol (GPI)
      anchor biosynthesis based on the fact that lack of this gene causes deficiencies
      of hundreds of GPI-anchored proteins. We previously demonstrated an essential
      role for the GPI-anchor in keratinocyte differentiation using male Pig-a knockout
      mice (K5-Cre:Pig-a flox). Here we analyzed keratinocytes of the female K5-Cre:
      Pig-a flox/+ mice with heterozygous knockout of Pig-a. These cells exhibited the
      mosaic pattern of GPI-anchor positive and negative expression typical of random
      inactivation of the X chromosome. The female K5-Cre:Pig-a flox/+ mice appeared
      slightly wrinkled with dry skin at birth and white scales starting from 4 d after
      birth without any histologic abnormality. This phenotype was temporary and milder
      than that seen in the male knockout mice. To characterize the fate of GPI-anchor
      positive cells more clearly, we introduced a transgenic mouse line that expresses
      enhanced green fluorescent protein in GPI-anchored form into female K5-Cre:Pig-a
      flox/+ mice and monitored GPI-anchor-positive keratinocytes in situ. Within 36 h
      after birth, the upper layer of the GPI-anchor-negative zone in epidermis was
      replaced by the GPI-anchor-positive counterpart. This tissue replacement was
      accompanied by recovery in trans-epidermal water loss over a similar time course.
      These observations suggest that the GPI-anchoring is associated with the barrier
      function as well as with organized differentiation of the epidermis after birth.

PMID- 12060395
TI  - C-5 propyne-modified oligonucleotides penetrate the epidermis in psoriatic and
      not normal human skin after topical application.
AB  - We have previously shown that antisense oligonucleotides effectively reduced
      insulin-like growth factor I receptor expression in human psoriatic skin grafted
      on to nude mice when injected intradermally. We therefore investigated the
      penetration of C-5 propyne modified antisense oligonucleotides into human normal
      and psoriatic skin after topical administration. Oligonucleotide (37.5 microg;
      250 microM) was applied in aqueous solution or 5% methylcellulose gel for 24 h,
      prior to live confocal microscopy and fluorescence microscopy of fixed sections.
      We found that oligonucleotide could penetrate through the stratum corneum of
      psoriatic but not normal human skin over large regions of the epidermis. The
      oligonucleotide was localized to the nucleus of large parakeratotic cells in the
      psoriatic skin as well as smaller basal and suprabasal keratinocytes. In normal
      human skin, oligonucleotide was confined to the stratum corneum, with little or
      no oligonucleotide apparent in the viable epidermis. Electrophoresis of
      oligonucleotide recovered from treated psoriatic and normal skin revealed that
      the oligonucleotide remained intact over the 24 h period. In summary, we found
      that C-5 propyne modified antisense oligonucleotides could reach the target cells
      (in this case basal keratinocytes) after topical administration to psoriatic but
      not normal skin.

PMID- 12060396
TI  - Selective peroxidation and externalization of phosphatidylserine in normal human
      epidermal keratinocytes during oxidative stress induced by cumene hydroperoxide.
AB  - Reactive oxygen species not only modulate important signal transduction pathways,
      but also induce DNA damage and cytotoxicity in keratinocytes. Hydrogen peroxide
      and organic peroxides are particularly important as these chemicals are widely
      used in dermally applied cosmetics and pharmaceuticals, and also represent
      endogenous metabolic intermediates. Lipid peroxidation is of fundamental interest
      in the cellular response to peroxides, as lipids are extremely sensitive to
      oxidation and lipid-based signaling systems have been implicated in a number of
      cellular processes, including apoptosis. Oxidation of specific phospholipid
      classes was measured in normal human epidermal keratinocytes exposed to cumene
      hydroperoxide after metabolic incorporation of the fluorescent oxidation
      sensitive fatty acid, cis-parinaric acid, using a fluorescence high-performance
      liquid chromatography assay. In addition, lipid oxidation was correlated with
      changes in membrane phospholipid asymmetry and other markers of apoptosis.
      Although cumene hydroperoxide produced significant oxidation of cis-parinaric
      acid in all phospholipid classes, one phospholipid, phosphatidylserine, appeared
      to be preferentially oxidized above all other species. Using fluorescamine
      derivatization and annexin V binding it was observed that specific oxidation of
      phosphatidylserine was accompanied by phosphatidylserine translocation from the
      inner to the outer plasma membrane surface where it may serve as a recognition
      signal for interaction with phagocytic macrophages. These effects occurred much
      earlier than any detectable changes in other apoptotic markers such as caspase-3
      activation, DNA fragmentation, or changes in nuclear morphology. Thus, normal
      human epidermal keratinocytes undergo profound lipid oxidation with preference
      for phosphatidylserine followed by phosphatidylserine externalization upon
      exposure to cumene hydroperoxide. It is therefore likely that normal human
      epidermal keratinocytes exposed to similar oxidative stress in vivo would under
      go phosphatidylserine oxidation/translocation. This would make them targets for
      macrophage recognition and phagocytosis, and thus limit their potential to invoke
      inflammation or give rise to neoplastic transformations.

PMID- 12060397
TI  - Inducible nitric oxide synthase is expressed in normal human melanocytes but not
      in melanoma cells in response to tumor necrosis factor-alpha, interferon-gamma,
      and lipopolysaccharide.
AB  - Nitric oxide is a gaseous messenger involved in the regulation of several
      physiologic processes in various cell types, including skin cells. Three
      different nitric oxide synthases (neuronal nitric oxide synthase, endothelial
      nitric oxide synthase, inducible nitric oxide synthase) have been identified in
      human cells. For inducible nitric oxide synthase, an inducibility by cytokines
      and lipopolysaccharides have been found. For murine melanoma cells, a connection
      between elevated levels of nitric oxide after inducible nitric oxide synthase
      induction and consequent apoptosis had been described. By northern analysis, we
      detected inducible nitric oxide synthase mRNA in four of 15 human melanoma cell
      lines cultured without inducible nitric oxide synthase inducing cytokines.
      Induction of inducible nitric oxide synthase mRNA by tumor necrosis factor-alpha,
      interferon-gamma, and lipopolysaccharides was seen in normal human melanocytes
      but not in melanoma cell lines. In accordance, inducible nitric oxide synthase
      protein expression was clearly inducible in cultures of normal melanocytes,
      whereas in six melanoma cell lines investigated, inducible nitric oxide synthase
      was found weakly expressed already before treatment with tumor necrosis factor
      alpha, interferon-gamma, and lipopolysaccharides, and its expression was not
      inducible. The apoptotic rates both in normal melanocytes and in two melanoma
      cell lines (SK-Mel-19 and O-Mel-2) were increased by treatment with tumor
      necrosis factor-alpha, interferon-gamma, and lipopolysaccharides; however, these
      effects could not be prevented by the specific nitric oxide synthase inhibitor
      N(G)-monomethyl-L-arginine. These data reveal a clear-cut difference between
      human melanoma cell lines and cultured normal human melanocytes with respect to
      inducible nitric oxide synthase inducibility. Although the data do not support
      the hypothesis that inducible nitric oxide synthase is an important regulator for
      apoptosis in human melanoma cells, the regulation deficiency found for melanoma
      cells may be of importance for melanocytic transformation and tumor progression.

PMID- 12060398
TI  - TP53 polymorphism of exon 4 at codon 72 in cutaneous squamous cell carcinoma and
      benign epithelial lesions of renal transplant recipients and immunocompetent
      individuals: lack of correlation with human papillomavirus status.
AB  - A common polymorphism at codon 72 of exon 4 encoding either arginine or proline
      has been shown to confer a susceptibility to the development of skin tumor in
      renal transplant recipients. Moreover, this polymorphism may affect proteolytic
      degradation of p53 promoted by E6 protein from mucosal human papillomaviruses and
      represent a risk factor for human-papillomavirus-induced carcinogenesis. In this
      study, we analyzed the human papillomavirus presence and the TP53 allele
      distribution in cutaneous squamous cell carcinoma of renal transplant recipients
      and immunocompetent patients. Fifty-three squamous cell carcinomas from 40 renal
      transplant recipients, 50 benign epithelial skin lesions from 50 renal transplant
      recipients with no history of skin cancer, 51 squamous cell carcinomas from
      immunocompetent patients, and 29 blood samples from immunocompetent individuals
      without skin cancer were investigated. Human papillomavirus DNA was detected
      using polymerase chain reaction performed with two pairs of primers (MY09-MY11
      and FAP59-FAP64). TP53 allele distribution was studied by denaturing gradient gel
      electrophoresis assay, followed by sequencing analysis. Human papillomavirus DNA
      was detected in 64% of squamous cell carcinoma and 79% of benign epithelial
      lesions from renal transplant recipients (NS) and only in 37% of squamous cell
      carcinoma from immunocompetent patients (p < 0.05). Mucosal oncogenic human
      papillomavirus types were predominant in squamous cell carcinoma from both renal
      transplant recipients and immunocompetent patients. Rate of arginine homozygosity
      in squamous cell carcinoma from renal transplant recipients was significantly
      higher (83%) than in immunocompetent patients with or without squamous cell
      carcinoma (60% and 59%, respectively). Our results suggest that TP53
      arginine/arginine genotype could represent a potential risk factor for the
      development of squamous cell carcinoma in renal transplant recipients compared to
      immunocompetent patients. No association between TP53 arginine/arginine genotype
      and human papillomavirus status could be determined, however.

PMID- 12060399
TI  - Ultraviolet a augments solar-simulated ultraviolet radiation-induced local
      suppression of recall responses in humans.
AB  - Many studies support the role of ultraviolet B in sunlight-induced alteration of
      the cutaneous immune system. The role of ultraviolet A is less clear,
      particularly in humans. The aim of this study was to determine the effect of
      additional ultraviolet A on solar-simulated ultraviolet-induced suppression of
      recall responses to nickel in humans. Immuno suppression dose-responses were
      induced in volunteers by exposure to solar-simulated ultraviolet radiation for
      four consecutive days. The ultraviolet A radiation dose was increased daily by
      providing additional high-dose ultraviolet A either before, or after the solar
      simulated ultraviolet radiation. These ultraviolet A doses can be readily
      achieved through a sunscreen. Two different ultraviolet A spectra were used; 320
      400 nm and 330-400 nm. Ultraviolet A alone did not cause significant
      immunosuppression, but augmented solar-simulated ultraviolet radiation-induced
      immunosuppression. Additional ultraviolet A reduced the minimum dose of solar
      simulated ultraviolet radiation that was immunosuppressive. Both ultraviolet A
      spectra had this effect, although photoaugmentation was less pronounced with the
      330-400 nm spectrum. Ultraviolet A-induced immediate pigment darkening did not
      protect from solar-simulated ultraviolet radiation-induced immuno suppression.

PMID- 12060400
TI  - Incidence and risk factors associated with a second squamous cell carcinoma or
      basal cell carcinoma in psoralen + ultraviolet a light-treated psoriasis
      patients.
AB  - Psoralen + ultraviolet A-treated psoriasis patients are at increased risk for
      squamous cell carcinomas and basal cell carcinomas; however, the incidence and
      risk factors associated with second squamous cell carcinomas and basal cell
      carcinomas in this population are not well qualified. Incidence and risk factors
      for second squamous cell carcinomas and basal cell carcinomas were studied in a
      cohort of 1380 psoralen + ultraviolet A-treated psoriasis patients prospectively
      followed for over 20 y; 264 had a squamous cell carcinoma and 258 a basal cell
      carcinoma after beginning psoralen + ultraviolet A therapy. After a first
      squamous cell carcinoma, the risk of a second squamous cell carcinoma was 26% at
      1 y, 62% at 5 y, and 75% at 10 y. Risk increased with high psoralen + ultraviolet
      A exposure prior to the first squamous cell carcinoma (hazard ratio 3.32, 95%
      confidence interval 1.53, 7.18). Higher rates of post-first squamous cell
      carcinoma psoralen + ultraviolet A treatment also were associated with greater
      risk (hazard ratio 1.56 for every additional 10 treatments per year for patients
      with low pre-first squamous cell carcinoma psoralen + ultraviolet A exposure, 95%
      confidence interval 1.35, 1.81). Patients exposed to high levels of tar and/or
      ultraviolet B before a first squamous cell carcinoma were also at higher risk
      (hazard ratio 1.72, 95% confidence interval 1.14-2.60). Risk of a second basal
      cell carcinoma was 21% at 1 y, 49% at 5 y, and 61% at 10 y. There was some
      evidence that high exposure to psoralen + ultraviolet A before a first basal cell
      carcinoma was associated with increased risk of second basal cell carcinoma
      (hazard ratio 1.45, 95% confidence interval 0.97-2.17). Higher post-first tumor
      psoralen + ultraviolet A treatment rates also increased risk (hazard ratio 1.24
      for every additional 10 treatments per year, 95% confidence interval 1.06-1.47).
      Psoralen + ultraviolet A-treated psoriasis patients appear to have a greatly
      increased incidence of second squamous cell carcinoma compared with the general
      population. Patients who develop a squamous cell carcinoma after starting
      psoralen + ultraviolet A therapy should be closely monitored for a subsequent
      squamous cell carcinoma.

PMID- 12060401
TI  - Positive atopy patch test reaction to Malassezia furfur in atopic dermatitis
      correlates with a T helper 2-like peripheral blood mononuclear cells response.
AB  - The yeast Malassezia furfur belongs to the normal cutaneous flora, but is also a
      triggering allergen that can contribute to atopic dermatitis. To illuminate the
      effect of circulating allergen-specific T cells in atopic dermatitis, the
      peripheral mononuclear cell response was correlated with the in vivo skin prick
      test and atopy patch test reactivity to M. furfur. None of 16 healthy controls
      showed any positive in vivo reaction. The 40 atopic dermatitis patients, of whom
      18 had serum IgE reactivity to M. furfur, were subdivided according to their in
      vivo reaction to M. furfur extract into three groups: skin prick test
      positive/atopy patch test positive (n = 12), skin prick test positive/atopy patch
      test negative (n = 12), and skin prick test negative/atopy patch test negative (n
      = 16). The skin prick test positive/atopy patch test positive and the skin prick
      test positive/atopy patch test negative groups had a significantly higher
      peripheral mononuclear cell stimulation index than the healthy controls.
      Interestingly, the stimulation index values in the skin prick test positive/atopy
      patch test positive group were significantly higher than in the skin prick test
      positive/atopy patch test negative group. In the M. furfur skin prick test
      positive atopic dermatitis patients (n = 24) a correlation was found between
      stimulation index and the M. furfur atopy patch test reactions, but not between
      stimulation index and M. furfur-specific serum IgE levels. Skin prick test
      positive and/or atopy patch test positive reactions to the recombinant M. furfur
      allergens rMal f 1, rMal f 5, and rMal f 6 were observed in 7, 14, and 16 of the
      40 atopic dermatitis patients, respectively. Further, there was a correlation
      between production of the T helper 2-related cytokines interleukins 4, 5, and 13
      and stimulation index to M. furfur extract, but not between the T helper 1
      related interferon-gamma and stimulation index to M. furfur extract. Our data
      strongly suggest a relationship between circulating specific T cells with a T
      helper 2-like cytokine profile and positive atopy patch test reactions.

PMID- 12060402
TI  - Nickel-specific CD4(+) and CD8(+) T cells display distinct migratory responses to
      chemokines produced during allergic contact dermatitis.
AB  - Development of allergic contact dermatitis to haptens depends upon a balance
      between CD8(+) T lymphocytes with pathogenic activity and CD4(+) T cells, which
      comprise both effector and regulatory cells. Thus, differential recruitment of
      CD8(+) and CD4(+) lymphocytes to sites of hapten challenge may have considerable
      impact on disease expression. Here the migration of cutaneous lymphocyte
      associated antigen+, nickel-specific CD8(+) and CD4(+) T cell lines were compared
      with a panel of chemokines produced in the skin during allergic contact
      dermatitis. CCL17/TARC and CCL22/MDC induced a 3-fold higher migration of CD4(+)
      compared with CD8(+) lymphocytes. In contrast, CXCL10/IP-10 was 2-fold more
      potent in attracting CD8(+) cells. These findings were consistent with the higher
      expression of CCR4 and CXCR3 on CD4(+) and CD8(+) T cell lines, respectively.
      Moreover, CCR4 expression was high on nickel-specific T helper 2, intermediate on
      T helper 1 and T cytotoxic 2, and almost undetectable on T cytotoxic 1 clones. On
      the contrary, CXCR3 was expressed by T cytotoxic 1 and 2 and T helper 1, but not
      T helper 2 clones. Reverse transcription-polymerase chain reaction analysis of
      the skin before and after hapten challenge revealed the constitutive presence of
      TARC, and the early appearance of CCL2/MCP-1, followed by IP-10, CCL4/MIP-1beta,
      and MDC mRNA. Supernatants from activated keratinocytes induced a strong
      migration of CD8(+) lymphocytes, which was blocked by neutralization of IP-10.
      Conversely, supernatants from immature and mature dendritic cells attracted
      mostly CD4(+) lymphocytes in a TARC- and MDC-dependent manner. Our data indicate
      that distinct chemokines and cell types control the accumulation of CD8(+) and
      CD4(+) T cells within inflamed skin.

PMID- 12060403
TI  - The epidermolysis bullosa acquisita antigen (type VII collagen) is present in
      human colon and patients with crohn's disease have autoantibodies to type VII
      collagen.
AB  - Epidermolysis bullosa acquisita is an autoimmune blistering disease of the skin
      characterized by IgG autoantibodies against type VII collagen. Systemic diseases
      are often associated with epidermolysis bullosa acquisita, Crohn's disease being
      the most frequent. This study sought to determine if type VII collagen, the
      epidermolysis bullosa acquisita autoantigen, was present in normal human colon by
      western blotting and immunofluorescence. The 290 kDa type VII collagen alpha
      chain was demonstrated by western blotting in four normal intraoperative colon
      specimens. Antibodies to type VII collagen labeled the junction between the
      intestinal epithelium and the lamina propria. We also used an enzyme-linked
      immunosorbent assay to test sera from patients with Crohn's disease (n = 19),
      ulcerative colitis (n = 31), celiac disease (n = 17), rheumatoid arthritis (n =
      15), and normal controls (n = 16). It was found that 13 of 19 patients with
      Crohn's disease and four of 31 patients with ulcerative colitis demonstrated
      reactivity to type VII collagen. Sera from control subjects, patients with celiac
      disease or rheumatoid arthritis were negative. The sera from Crohn's disease
      patients also reacted with type VII collagen by immunoblot analysis. It was
      concluded that patients with inflammatory bowel disease may have IgG
      autoantibodies to type VII collagen, which exists in both the skin and the gut.

PMID- 12060404
TI  - Corticotropin releasing factor receptor type 1: molecular cloning and
      investigation of alternative splicing in the hamster skin.
AB  - The coding region of the hamster corticotropin releasing factor receptor type 1
      was sequenced. Hamster gene appeared to be similar to mouse, rat, and human
      sequences with 95%, 94%, and 91% homology, respectively. Protein substitutions
      were generally found in the corticotropin releasing factor-binding domain. Thus,
      this domain can be more prone to mutations leading to changes in amino acid
      sequence. Hamster pituitary, eye, spleen, heart, skin, and four melanoma lines
      differentially expressed nine corticotropin releasing factor-R1 isoforms. These
      included the corticotropin releasing factor-R1alpha and corticotropin releasing
      factor-R1d homologs of human isoforms as well as e, f, h, j, k, m, and n
      isoforms. Corticotropin releasing factor-R1e mRNA had deletion of exons 3 and 4,
      CRF-R1j of exon 5, CRF-R1f of exon 11, CRF-R1k of exon 10, CRF-R1m of exons 11
      and 12, and CRF-R1n of exons 10, 11, and 12. Corticotropin releasing factor-R1h
      had an insertion of a cryptic exon between exons 4 and 5. Reading frames of
      isoforms e, f, j, k, m, and h contained frameshifts, expected to produce
      truncated proteins. Corticotropin releasing factor-R1n isoform preserved the
      reading frame, but the transmembrane domains 6, 7, and one-third of the fifth
      were deleted. The AbC1 hamster melanoma cell line changed the pattern of
      alternative splicing after irradiation with ultraviolet light or induction of
      melanogenesis; this suggests that corticotropin releasing factor receptor
      alternative splicing may be regulated by common stressors, through modifications
      of activity and/or availability of splicing factors.

PMID- 12060406
TI  - Expression of T-cadherin in Basal keratinocytes of skin.
AB  - T-cadherin is a unique member of the cadherin superfamily that shares the
      ectodomain organization with classical cadherins, but lacks both transmembrane
      and cytoplasmic regions and is instead anchored to the plasma membrane through a
      glycosyl-phosphatidylinositol (GPI) moiety. The function of T-cadherin has not
      been revealed yet. The special structure of T-cadherin might endow this molecule
      with specific intracellular targeting properties and functions that are distinct
      from classical cadherins. T-cadherin was originally cloned from chicken embryo
      brain and then was also found in mouse and human nervous and cardiovascular
      systems; however, T-cadherin in the keratinocytes and skin tissue is still an
      unknown area that remains to be explored. To test whether the unusual truncated T
      cadherin is expressed in keratinocytes, we performed the reverse transcriptase
      polymerase chain reaction of T-cadherin, as well as several classical cadherins
      (E-, P-, and N-cadherin), on the mouse keratinocyte cell line Pam212, fibroblast
      NIH3T3, and melanoma cell B16. The result indicated that mouse keratinocytes
      expressed the mRNA of truncated T-cadherin apart from classical cadherins, E-,
      and P-cadherin. To confirm the expression of T-cadherin in mouse keratinocytes,
      immunocytochemistry staining was carried out on Pam212 cells by using rabbit anti
      T-cadherin antibody and rat antimouse E- and P-cadherin antibody. The result of
      immunofluorescence staining proved that T-cadherin was expressed in mouse
      keratinocytes. In order to analyze the distribution patterns of T-cadherin and
      classical cadherins on the keratinocytes, 3D scanning was performed by using a
      confocal microscope. From the Z-sections and XZ-sections, it was clearly
      demonstrated that T-cadherin was distributed diffusely on the whole cell surface,
      while E- and P-cadherin were concentrated on the cell-cell contacts. To examine
      the expression and the localization of T-cadherin on skin tissue, the frozen
      sections of the mouse back skin were immunohistochemically labeled by using anti
      T-cadherin antibody. It was found that T-cadherin was intensively expressed only
      on the basal cell layer of the mouse skin. Apart from mouse keratinocytes and
      mouse skin, we further examined the expression of T-cadherin in human
      keratinocytes and human skin by western blot, immunocytochemistry, and
      immunohistochemistry staining. The same results were achieved with human samples.
      In this study, we found and verified that T-cadherin was expressed on the mouse
      and human keratinocytes and specifically localized on the basal cell layer of
      skin. The nature of T-cadherin function and its mechanism of localization at the
      basal cell layer of skin are important issues to be addressed concerning this
      unique member of the cadherin family and its physiologic and pathologic roles in
      the skin.

PMID- 12060405
TI  - Molecular architecture of tight junctions of periderm differs from that of the
      maculae occludentes of epidermis.
AB  - Occludin and claudins are tetraspan-transmembrane proteins in tight junctions.
      Maculae occludentes, which are less-developed tight junctions, occur in the
      granular cell layer of the epidermis. The periderm, which overlies the developing
      epidermis and functions as a protective layer for the embryo, carries developed
      tight junctions as observed in simple epithelia. In both periderm and epidermis,
      occludin is expressed at the cell-cell border. To determine the difference
      between tight junctions of periderm and epidermis, claudin-6 expression was
      examined in periderm and epidermis. Immunofluorescence staining showed claudin-6
      expression at the cell-cell border of the periderm, but not in the epidermis.
      Reverse transcription-polymerase chain reaction confirmed that claudin-6 was not
      expressed in mouse adult skin, whereas immunoelectron microscopy revealed that
      claudin-6 was localized at tight junctions of the periderm. Furthermore, L
      fibroblasts with stable expression of exogenous claudin-6 formed developed tight
      junctions at cell-cell borders. These findings indicate that molecular
      architecture of tight junctions of the periderm is different from that of the
      maculae occludentes of the epidermis, and that claudin-6 is important in the
      formation of tight junctions of the periderm.

PMID- 12060407
TI  - Topographic heterogeneity in transdermal transport revealed by high-speed two
      photon microscopy: determination of representative skin sample sizes.
AB  - A novel application of high-speed two-photon microscopy was utilized to determine
      the optimum number of skin sites required to accurately determine the changes in
      transdermal transport properties incurred globally, over a clinically relevant
      area of skin. In contrast to the four to six skin sites (100 microm by 100 mirom
      area per site) examined previously, this study accounted for the fluorescent
      probe distributions at 400 consecutive skin sites, covering a total skin area of
      2 mm by 2 mm. The oleic-acid-induced changes in the transdermal transport
      properties of the model hydrophobic probe, rhodamine B hexyl ester, and of the
      model hydrophilic probe, sulforhodamine B, for this 400-skin-site study exhibited
      different dependencies on sample size for each probe. Whereas the examination of
      six skin sites captures the relative changes in the global transdermal transport
      properties of the hydrophobic probe, the valid assessment of these changes for
      the hydrophilic probe requires a significantly larger sample size of at least 24
      skin sites.

PMID- 12060409
TI  - Critical advances in the evaluation and development of clinical care.

PMID- 12060410
TI  - The evolving paradigm of evidence-based medicine.

PMID- 12060411
TI  - Will clinicians' challenges be solved by another theoretical model? Commentary on
      Sweeney & Kernick (2002), Clinical evaluation: constructing a new model for post
      normal medicine. Journal of Evaluation in Clinical Practice 8, 131-138.

PMID- 12060412
TI  - Commentary on Sweeney & Kernick (2002), Clinical evaluation: constructing a new
      model for post-normal medicine. Journal of Evaluation in Clinical Practice 8, 131
      138.

PMID- 12060413
TI  - Evidence-based medicine, guidelines, personality types, relatives and absolutes.
AB  - There is an epidemic of guidelines but very little evidence-based information has
      been assembled to tell us exactly how guidelines are best implemented.
      Guidelines, although very valuable, are essentially a reductionistic attempt to
      simplify the complexities of medicine. Clinicians may appreciate that each
      guideline should be prefaced by a statement that 'what follows may not be
      applicable to all patients' but there seems little doubt that guideline adherence
      will be used to assess quality of care by those unfamiliar with the complexities.

PMID- 12060414
TI  - An explanatory model of medical practice variation: a physician resource demand
      perspective.
AB  - Practice style variation, or variation in the manner in which physicians treat
      patients with a similar disease condition, has been the focus of attention for
      many years. The research agenda is further intensified by the unrealistic
      assumption that by reducing variation, quality will be improved, costs will be
      reduced, or both. There is a wealth of literature that identifies differences in
      health care use of many kinds, in apparently similar communities. Attempts have
      been made by many scholars to identify the determinants of variation in terms of
      differences in the population characteristics (e.g. age, sex, insurance, etc.)
      and geographical characteristics (e.g. distance to provider, number of
      physicians, number of hospital beds, etc.). When significant differences in use
      rates prevail after controlling for differences in population characteristics, it
      is often attributed to 'uncertainty', or the fact that there is no consensus on
      what constitutes the optimum treatment process. It is suggested by this
      literature that the greatest variation can be found in the circumstances where
      there is the most 'uncertainty'. In this work, a physician resource demand model
      is proposed in which it is suggested that, during the diagnosis and treatment
      process, physicians demand resources consistent with the clinical needs of the
      patients, modified by the intervening forces under which they practice. These
      intervening forces, or constraints, are categorized as patient agency
      constraints, organizational constraints and environmental constraints, which are
      characterized as 'induced variation'. It is suggested that when all of the
      variables that constitute these constraints are identified, the remaining
      variance represents 'innate variance', or practice style differences. It is
      further suggested that the more completely this model is specified, the more
      likely area differences will be attenuated and the smaller will be the residual
      variance.

PMID- 12060415
TI  - Measuring outcomes with tools of proven feasibility and utility: the example of a
      patient-focused asthma measure.
AB  - Best quality care is clearly desirable and instituting quality assurance should
      be logical and simple. However, the practicality of setting standards for a
      product or service, and designing systems to measure against the standards, is
      more difficult. In the health service it is only likely to be feasible if data
      can be generated from efficient and reliable information systems. The ideal
      measure of quality is an outcome measure that evaluates whether or not the
      quality of care has achieved the desired standard of outcome. Direct measures of
      outcome are not easy to construct and the information systems required to provide
      data are not widely available. The National Centre for Health Outcomes
      Development (NCHOD) has produced a series of indicators in 10 areas of health
      care, where an indicator is a pointer to, rather than a direct measure of, a
      desired outcome. Feasibility studies measuring their sensitivity and reliability
      have drawn attention to their possible utility within different health care
      settings. This paper reports on an investigation into a patient-focused outcome
      indicator for asthma. There is broad agreement about the need to measure the
      outcome of disease. However, when outcome indicators are defined there are major
      obstacles to their successful uptake. A key challenge for outcomes measurement is
      to ensure that the cost of collecting the data and ensuring completeness,
      accuracy and standardization are justified by the benefits derived. Health
      outcome indicators should not be treated as a panacea, but as a part of the
      clinical and health care tool kit.

PMID- 12060417
TI  - Bayeswatch: an overview of Bayesian statistics.
AB  - Increasingly, clinical research is evaluated on the quality of its statistical
      analysis. Traditionally, statistical analyses in clinical research have been
      carried out from a 'frequentist' perspective. The presence of an alternative
      paradigm - the Bayesian paradigm - has been relatively unknown in clinical
      research until recently. There is currently a growing interest in the use of
      Bayesian statistics in health care research. This is due both to a growing
      realization of the limitations of frequentist methods and to the ability of
      Bayesian methods explicitly to incorporate prior expert knowledge and belief into
      the analyses. This is in contrast to frequentist methods, where prior experience
      and beliefs tend to be incorporated into the analyses in an ad hoc fashion. This
      paper outlines the frequentist and Bayesian paradigms. Acute myocardial
      infarction mortality data are then analysed from both a Bayesian and a
      frequentist perspective. In some analyses, the two methods are seen to produce
      comparable results; in others, they produce different results. It is noted that
      in this example, there are clinically relevant questions that are more easily
      addressed from a Bayesian perspective. Finally, areas in clinical research where
      Bayesian ideas are increasingly common are highlighted.

PMID- 12060416
TI  - Using imprecise probabilities to address the questions of inference and decision
      in randomized clinical trials.
AB  - Randomized controlled clinical trials play an important role in the development
      of new medical therapies. There is, however, an ethical issue surrounding the use
      of randomized treatment allocation when the patient is suffering from a life
      threatening condition and requires immediate treatment. Such patients can only
      benefit from the treatment they actually receive and not from the alternative
      therapy, even if it ultimately proves to be superior. We discuss a novel new way
      to analyse data from such clinical trials based on the use of the recently
      developed theory of imprecise probabilities. This work draws an explicit
      distinction between the related but nevertheless distinct questions of inference
      and decision in clinical trials. The traditional question of scientific interest
      asks 'Which treatment offers the greater chance of success?' and is the primary
      reason for conducting the clinical trial. The question of decision concerns the
      welfare of the patients in the clinical trial, asking whether the accumulated
      evidence favours one treatment over the other to such an extent that the next
      patient should decline randomization and instead express a preference for one
      treatment. Consideration of the decision question within the framework of
      imprecise probabilities leads to a mathematical definition of equipoise and a
      method for governing the randomization protocol of a clinical trial. This paper
      describes in detail the protocol for the conduct of clinical trials based on this
      new method of analysis, which is illustrated in a retrospective analysis of data
      from a clinical trial comparing the anti-emetic drugs ondansetron and droperidol
      in the treatment of postoperative nausea and vomiting. The proposed methodology
      is compared quantitatively using computer simulation studies with conventional
      clinical trial designs and is shown to maintain high statistical power with
      reduced sample sizes, at the expense of a high type I error rate that we argue is
      irrelevant in some specific circumstances. Particular emphasis is placed on
      describing the type of medical conditions and treatment comparisons where the new
      methodology is expected to provide the greatest benefit.

PMID- 12060419
TI  - The effect of a fibrin glue on the integration of Bio-Oss with bone tissue. A
      experimental study in labrador dogs.
AB  - BACKGROUND: Bio-Oss is a deproteinized bovine mineral used in bone augmentation
      procedures. The particles are often mixed with a protein product (Tisseel) to
      form a mouldable graft material. AIM: The aim of the present experiment was to
      study the healing of self-contained bone defects after the placement of Bio-Oss
      particles alone or mixed with Tisseel in cylindrical defects in the edentulous
      mandibular ridge of dogs. MATERIAL AND METHODS: In 4 labrador dogs, the 2nd, 3rd
      and 4th mandibular premolars were extracted bilaterally. 3 months later, 3
      cylindrical bone defects, 4 mm in diameter and 8 mm in depth, were produced in
      the right side of the mandible. Following a crestal incision, full thickness
      flaps were raised and the bone defects were prepared with a trephine drill. The
      defects were filled with Bio-Oss (Geistlich Biomaterials, Wolhuser, Switzerland)
      particles alone or mixed with Tisseel (Immuno AG, Vienna, Austria), or left
      "untreated". A collagen membrane (Bio-Gide, Geistlich Biomaterials, Wolhuser,
      Switzerland) was placed to cover all defects and the flaps were sutured. 2 months
      later, the defect preparation and grafting procedures were repeated in the left
      side of the mandible. After another month, the animals were sacrificed and
      biopsies obtained from the defect sites. RESULTS: Bio-Oss-treated defects
      revealed a higher percentage of contact between graft particles and bone tissue
      than defects treated with Bio-Oss+ Tisseel (15% and 30% at 1 and 3 months versus
      0.4% and 8%, respectively). Further, the volume of connective tissue in the Bio
      Oss treated defects decreased from the 1 to the 3 month interval (from 44% to
      30%). This soft tissue was replaced with newly formed bone. In the Bio-Oss+
      Tisseel treated defects, however, the proportion of connective tissue remained
      unchanged between 1 and 3 months. CONCLUSION: The adjunct of Tisseel may
      jeopardize the integration of Bio-Oss particles with bone tissue.

PMID- 12060420
TI  - Granulocyte elastase, matrix metalloproteinase-8 and prostaglandin E2 in gingival
      crevicular fluid in matched clinical sites in smokers and non-smokers with
      persistent periodontitis.
AB  - BACKGROUND/AIMS: Smokers with persistent periodontitis may have granulocytes with
      impaired function. This study aimed to determine the levels of granulocyte
      elastase, matrix metalloproteinase-8 (MMP-8) and prostaglandin E2 (PGE2) in
      gingival crevicular fluid (GCF) in smokers and non-smokers with persistent
      periodontitis. METHODS: We analyzed GCF from 70 matched sites in 29 periodontitis
      and 6 gingivitis sites in 34 subjects, 17 smokers, and 17 non-smokers. We also
      analyzed separately GCF from 28 of these subjects, 14 smokers and 14 non-smokers
      in 14 matched periodontitis sites. The following measurements were made: elastase
      complexed to alpha1-antitrypsin (EA-alpha1AT) and MMP-8 with ELISA, functional
      elastase with a chromogenic substrate, and PGE2 with radioimmunoassay (125I RIA).
      The significance of the findings was determined with Mann-Whitney test. RESULTS:
      In the 29 matched periodontitis sites, smokers had significantly more functional
      elastase (p<0.005) and more EA-alpha1AT (p<0.05) than non-smokers. In the 14
      matched periodontitis sites in 14 smokers and 14 non-smokers, the former had
      significantly more functional elastase than the latter (p<0.001). A significant
      correlation was found between EA-alpha1AT and MMP-8 in smokers (p<0.05) and non
      smokers (p<0.001) and a positive correlation between levels of functional
      elastase and MMP-8 in non-smokers (r2=0.98; p<0.001). CONCLUSIONS: Granulocyte
      function seems to be impaired in smokers with persistent periodontitis. The cells
      react to the bacterial challenge by releasing serine proteases, which reflect the
      degradation of connective tissue. The risk of progression of the disease is
      therefore higher in smokers with persistent periodontitis than in non-smokers.

PMID- 12060421
TI  - The effect of a polyhexamethylene biguanide mouthrinse compared to an essential
      oil rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque
      regrowth.
AB  - OBJECTIVES: For various clinical applications, polyhexamethylene biguanide
      hydrochloride (PHMB) has been used for many years as an antiseptic in medicine.
      Recently, a 0.04% PHMB mouthwash was shown to inhibit plaque regrowth and to
      reduce oral bacterial counts. In this study, a 0.12% PHMB mouthrinse (A) was
      compared with a negative control placebo rinse (10% ethanol, flavour) (B), a
      positive control 0.12% chlorhexidine rinse (C), and a commercially available
      mouthrinse containing essential oils (Listerine) (D). MATERIALS AND METHODS: The
      study was a double-blind, randomised 4-replicate 4 x 4 Latin square cross-over
      design in which plaque regrowth was measured. The in vivo antibacterial effect
      was assessed by taking bacterial counts from the tooth surface and mucosa 4 h
      after the first rinse with the preparations on day 1 and prior to the clinical
      examination on day 5. 16 volunteers participated and, on day 1 of each study
      period, were rendered plaque-free, ceased toothcleaning, and rinsed 2x daily with
      the allocated mouthrinse. On day 5, plaque was scored and smears were collected
      according to the protocol. Washout periods were 9 days. Data were analysed using
      ANOVA with Bonferroni HSD adjustment for multiple comparisons (significance level
      alpha=0.05). RESULTS: The 0.12% PHMB mouthrinse (A) was significantly more
      effective in inhibiting plaque than the placebo (B) but no significant
      differences could be observed between A and 0.12% chlorhexidine (C), or between A
      and Listerine (D). Bacterial count reductions on the tooth surface with PHMB (A)
      were significantly greater compared to the placebo (B) after 4 h and
      significantly greater compared to B and D after 5 days. Chlorhexidine (C) was
      more effective than A after 5 days. On the mucosa, chlorhexidine (C) was
      significantly more effective in reducing bacterial counts than the other 3
      treatments at both time points investigated. PHMB (A) was significantly more
      effective in reducing bacterial counts than the placebo (B) after 4 h and after 5
      days, and than D after 4 h. CONCLUSION: Consistent with a previous study, a PHMB
      mouthrinse was shown to inhibit plaque recolonisation and to reduce oral
      bacterial counts, indicating that PHMB may find applications in the prevention of
      plaque-associated diseases.

PMID- 12060422
TI  - Periodontal diseases in the child and adolescent.
AB  - BACKGROUND: Periodontal diseases are among the most frequent diseases affecting
      children and adolescents. These include gingivitis, localized or generalized
      aggressive periodontitis (a.k.a., early onset periodontitis which includes
      generalized or localized prepubertal periodontitis and juvenile periodontitis)
      and periodontal diseases associated with systemic disorders. The best approach to
      managing periodontal diseases is prevention, followed by early detection and
      treatment. METHODS: This paper reviews the current literature concerning the most
      common periodontal diseases affecting children: chronic gingivitis (or dental
      plaque-induced gingival diseases) and early onset periodontitis (or aggressive
      periodontitis), including prepubertal and juvenile periodontitis. In addition,
      systemic diseases that affect the periodontium and oral lesions commonly found in
      young children are addressed. The prevalence, diagnostic characteristics,
      microbiology, host-related factors, and therapeutic management of each of these
      disease entities are thoroughly discussed.

PMID- 12060423
TI  - Salivary microbiota levels in relation to periodontal status, experience of
      caries and miswak use in Sudanese adults.
AB  - OBJECTIVES: The purpose of the present investigation was to assess the salivary
      levels of 25 oral bacteria in relation to periodontal status and experience of
      caries, and to compare the levels of these bacteria between habitual miswak and
      toothbrush users in adult Sudanese subjects. MATERIAL AND METHODS: The study
      subjects consisted of 56 individuals with age range 19-53 years (mean 35.2 years)
      and included 30 miswak and 26 toothbrush users. The periodontal status and
      presence of dental caries were assessed clinically. Whole saliva was collected
      from all subjects, and the levels of 25 selected bacterial species in saliva were
      assessed by the checkerboard DNA-DNA hybridization method using whole genomic DNA
      probes. RESULTS: A high percentage of the subjects had detectable levels (> or =
      105 bacterial cells) of several bacterial species in saliva. Between 12% and 16%
      of the subjects showed high (> or = 106 cells) salivary levels of the
      periodontitis-associated bacteria A. actinomycetemcomitans, P. melaninogenica, P.
      intermedia, C. rectus and E. corrodens, whereas only two (3.6%) and four (7.1%)
      subjects had high levels of P. gingivalis and F. nucleatum, respectively. There
      were no significant differences in the levels of all or most bacterial species by
      age group, gender or periodontal status. Presence of > or = 105 L. acidophilus
      bacterial cells in saliva was associated with high caries scores (p = 0.02).
      There were significantly higher levels of A. actinomycetemcomitans, P.
      melaninogenica, C. rectus, P. micros, V. parvula, S. mutans, S. anginosus, A.
      israelii, C. sputigena, and C. gingivalis, and significantly lower levels of P.
      intermedia, F. nucleatum, S. sputigena, E. corrodens, L. acidophilus, S. sanguis,
      S. salivarius, S. oralis, and S. mitis in the miswak than in the toothbrush
      group. CONCLUSIONS: : The findings suggest that miswak may have a selective
      inhibitory effect on the level of certain bacteria in saliva, particularly
      several oral streptococci species. This is the first report that the checkerboard
      DNA-DNA hybridization method can be useful for assessing the levels of a wide
      range of bacterial taxa in saliva.

PMID- 12060425
TI  - The theory of reasoned action in describing tooth brushing, dental caries and
      diabetes adherence among diabetic patients.
AB  - OBJECTIVES: Preventive oral health behaviour is important among diabetic
      patients, as it has been found that dental diseases and insulin-dependent
      diabetes mellitus (IDDM) have some psychological and biological factors in
      common. The aim here was to analyze the variables of Ajzen and Fishbein's theory
      of reasoned action to explain the reported frequency of tooth brushing, dental
      caries, HbA1c level and diabetes adherence. MATERIAL AND METHODS: Cross-sectional
      data were gathered from 149 IDDM patients by means of a quantitative
      questionnaire, clinical examination and patient records. RESULTS: The results
      showed that a firmer intention to brush the teeth was related to a higher
      reported frequency of tooth brushing (p < 0.001). The attitude to and the
      subjective norm of tooth brushing were related to the intention to brush(p <
      0.001) and to the reported frequency of tooth brushing. A better dental attitude
      was related to better diabetes adherence (p = 0.002) and fewer decayed surfaces
      (p = 0.01), and a firmer intention to brush the teeth was related to a lower
      HbA1c level (p = 0.015). CONCLUSIONS: Our results suggest that in oral health
      promotion among diabetic patients, both subjective norm and attitude are
      important and that diabetes adherence may be influenced by promoting dental
      attitude.

PMID- 12060424
TI  - Associations of serum concentrations of IgG, IgA, IgM and interleukin-1beta with
      early-onset periodontitis classification and race.
AB  - BACKGROUND: The significance of serum concentrations of various antibodies and
      cytokines in the pathogenesis of early-onset periodontitis (EOP) is not well
      understood. Recent reports suggest differences between young blacks and whites in
      certain humoral responses, regardless of periodontal status. This study was
      undertaken to compare the serum concentrations of IgG, IgA, IgM, and IL-1beta in
      EOP subjects with that of healthy controls, and to study the effect of race on
      these levels. MATERIAL AND METHODS: This case-control study included 228
      individuals, 19-25 years old who were selected from a larger population examined
      in the National Survey of Oral Health of United States Children in 1986/1987. The
      subjects were classified by their EOP status and they included 166 subjects with
      EOP and 62 healthy controls. Blood samples were used to assess the serum
      concentrations of IgG, IgM, IgA, IgG subclass, and IL-1beta. RESULTS: The serum
      concentrations of IgG, IgG subclasses, IgA, and IgM in blacks were not
      significantly different in the generalized, localized and incidental EOP groups
      as compared to the healthy controls. The serum IL-1beta concentration was
      slightly and uniformly lower in the EOP groups than in the control group,
      although not statistically significant. Blacks had significantly higher serum
      concentrations of total IgG, and of IgG1, IgG2 and IgG3 than whites and
      Hispanics. Hispanics had significantly higher serum concentrations of IgM and
      IgG4 than whites and blacks. Hispanics also had a significantly higher serum
      concentration of IL-1beta than blacks. CONCLUSIONS: Total antibody response in
      blacks is not associated with EOP classification. Race has a significant effect
      on serum antibody concentrations irrespective of disease classification, with
      blacks having significantly higher serum concentrations of IgG1, IgG2 and IgG3
      than whites and Hispanics.

PMID- 12060426
TI  - Supracrestal soft tissue preservation with enamel matrix proteins in treatment of
      deep intrabony defects.
AB  - BACKGROUND/AIMS: The purpose of the present study was to investigate the
      effectiveness of a regenerative procedure based on supracrestal soft tissue
      preservation in association with enamel matrix proteins (EMP) in the treatment of
      deep intrabony defects. METHODS: The subjects included 35 consecutively treated
      patients, 23 females and 12 males, aged 28-61 years, 11 of whom were smokers.
      Patients presented with at least one intrabony defect with probing pocket depth >
      or = 6 mm and a radiographic depth of the defect > or = 4 mm at the initial
      visit. Immediately before surgery and 9-12 months after surgery, Local Plaque
      Score (LPS), Local Bleeding Score (LBS), probing pocket depth (PPD), clinical
      attachment level (CAL), gingival recession (REC), and radiographic depth of the
      defect (DEPTH) were recorded. RESULTS: Thirty-one (88.6%) defects were LPS
      negative presurgery, while 29 (82.9%) defects presented with no plaque
      postsurgery. The prevalence of LBS-positive defects shifted from 94.3% presurgery
      to 8.4% postsurgery (p < 0.0000). PPD was 8.9 mm before surgery, and decreased to
      3.5 mm postsurgery (p < 0.0000). CAL varied from 10.1 mm presurgery to 5.4 mm
      postsurgery (p < 0.0000), with an average improvement (gain) of 4.7 +/- 1.7 mm.
      Twenty-six (74.3%) defects presented a gain of least 4 mm. Regression analysis
      showed a positive correlation between CAL gain as a dependent variable, and
      presurgery PPD and amount of supracrestal soft tissues as predictors. DEPTH
      improvement (gain) was 3.9 +/- 1.8 mm, which represented 65% of defect fill.
      Twenty (57.1%) defects presented a DEPTH gain of at least 4 mm. DEPTH gain was
      significantly correlated to presurgery PPD (p < 0.000). No significant
      differences were found between smokers and non-smokers in terms of CAL and DEPTH
      gain. CONCLUSIONS: Results from the present study indicated that the regenerative
      procedure based on supracrestal soft tissue preservation and EMP application
      leads to clinically and statistically significant improvement of hard and soft
      tissue conditions of deep intrabony defects.

PMID- 12060427
TI  - Can application of exogenous fibronectin enhance periodontal regeneration?
AB  - BACKGROUND: Although fibronectin (FN) is an important extracellular glycoprotein
      involved in periodontal wound healing, it is not clear whether the application of
      exogenous fibronectin (ExoFN) offers any clinical benefit. The purpose of this
      preliminary in vitro study was to determine the binding of FN from three
      different sources, viz. endogenous EDTA-plasma, endogenous serum and exogenous
      commercial purified human fibronectin in PBS buffer, to demineralized and non
      demineralized root powder. METHOD: The binding of FN to a known quantity of
      mineralized and non-demineralized root powder by overnight incubation at 15
      degrees C was studied by enzyme immunoassay (EIA) technique. The criteria for
      optimal performance of EIA procedure for the determination of FN was established.
      Particle size of powdered root structure was standardized using a Vibratory Sieve
      Shaker. RESULTS: The EDTA-plasma and the serum FN exhibited binding of (17.8 +/-
      2.1 microg) and (6.5 +/- 4.5 microg), respectively, to the non-demineralized root
      powder. However, the binding was only significant for the EDTA-plasma FN (p <
      0.01) when compared to controls. In the demineralized group there was no
      ascertainable binding of FN from either endogenous or exogenous sources. ExoFN in
      buffer exhibited no binding at all to the non-demineralized or demineralized root
      powder. CONCLUSION: The preliminary data suggest that additional plasma and serum
      factors may facilitate the binding of FN to root powder. High levels of FN in
      blood do not necessarily indicate that FN is available for binding to the root
      surface during periodontal surgery.

PMID- 12060428
TI  - The mucosal attachment to titanium implants with different surface
      characteristics: an experimental study in dogs.
AB  - BACKGROUND: Findings from in vitro studies have indicated that the orientation
      and proliferation of cells on titanium surfaces may be influenced by the
      topography of the surface on which they are grown. It may be argued, therefore,
      that differences may occur in the mucosal attachment to titanium implants with
      different surface roughness. AIM: The present experiment was performed to study
      the composition of the soft tissue barrier that formed to implants prepared with
      well-defined smooth or rough surfaces. MATERIAL AND METHODS: Five beagle dogs
      were used. Four implants made of c.p. titanium were placed in the right
      edentulous mandibular premolar region. After 3 months, two different types of
      abutments were connected: one experimental (OA) with a dual, thermal acid-etched
      surface ('Osseotite'), and one regular (RA) abutment with a 'turned' surface. At
      the end of a 6-month period during which proper plaque control had been
      maintained, biopsies including the implant and the surrounding soft and hard
      tissues were obtained, decalcified and processed for light and electron
      microscopy. A confocal He-Ne laser profilometer was used to study the surface
      topography of the abutments. RESULTS: The attachment between the peri-implant
      mucosa and titanium abutments with either a turned (RA; 'smooth') or acid-etched
      (OA; 'rough') surface was similar from both a quantitative and a qualitative
      aspect. The attachment comprised a barrier epithelium and a zone of connective
      tissue attachment of similar dimension at RA and OA. It was further observed that
      the 'inner' zone of the connective tissue attachment at both types of abutment
      was composed of about 30-33% fibroblasts and 63-66% collagen. CONCLUSION: It was
      demonstrated that the soft tissue attachment that formed to implants made of c.p.
      titanium was not influenced by the roughness of the titanium surface.

PMID- 12060429
TI  - Soft tissue reactions to plaque formation at implant abutments with different
      surface topography. An experimental study in dogs.
AB  - BACKGROUND: The mucosal attachment that forms to titanium implants,
      uncontaminated by bacterial plaque comprises, independent of the surface
      characteristics of the abutment, one barrier epithelium and one zone of
      connective tissue attachment. It was suggested that abutments with a rough
      surface may accumulate more plaque than abutments with a smooth surface and that
      such an enhanced rate of plaque build-up may favor the development of
      inflammatory lesions in the periimplant mucosa. OBJECTIVES: The aim of the
      present experiment was to study some reactions of the periimplant mucosa to
      plaque accumulation on implant abutments designed with either a rough or a smooth
      external surface. MATERIAL AND METHODS: In five beagle dogs, four fixtures were
      placed and submerged in the premolar region. In a second stage procedure
      performed after 3 months, abutments with two different types of surface
      topography, one rough, acid-etched (OA) and one smooth, turned abutment (TA),
      were installed in a random order. After 6 months of undisturbed plaque formation,
      the animals were sacrificed and biopsies obtained. Tissue samples were prepared
      for light microscopy and exposed to histometric and morphometric measurements.
      RESULTS: Six months of plaque accumulation resulted in the establishment of an
      inflammatory lesion (pl-ICT) in the connective tissue of the periimplant mucosa,
      the location, size and composition of which did not differ between OA and TA
      sites. In addition, most OA and TA sites harbored a second inflammatory cell
      infiltrate in the tissue lateral to the abutment/fixture junction (ab-ICT). While
      pl-ICT was dominated by plasma cells and lymphocytes, ab-ICT contained a
      comparatively large number of polymorphonuclear leukocytes. CONCLUSION: The
      different surface characteristics of abutment made of c.p. titanium failed to
      influence plaque formation and the establishment of inflammatory cell lesions in
      the periimplant mucosa.

PMID- 12060430
TI  - In vitro antioxidant activities of mouthrinses and their components.
AB  - OBJECTIVES: Several forms of periodontal diseases (PD) are often associated with
      activated phagocytosing leukocytes and contemporary free radical production. Host
      antioxidant defenses could benefit from mouthrinses used as adjuncts to
      counteract plaque-associated bacteria. The aim of the present study was to
      determine possible antioxidant activity (AA) of a number of antiseptic
      mouthrinses and of their stated active principles (AP), regardless of their
      efficacy as antimicrobial agents. MATERIAL AND METHODS: The antioxidant
      activities of 11 mouthrinses and their active principles were tested with a
      specific spectrophotometric method. Comet assay was used to test whether pure
      chemical antioxidant activity actually corresponded to prevention of in vitro DNA
      fragmentation. RESULTS: Methylsalicylate-containing mouthrinses were the most
      effective. Several compounds, and some vehicles, behaved as antioxidants.
      Fibroblast DNA fragmentation was limited by preincubation with methylsalicylate
      containing mouthrinse but was unaffected by treatment with chlorexidine.
      CONCLUSION: The results described herein indicate that several mouthrinses
      possess AA; such a property could be ascribed to either AP or vehicles or both.
      All the data were obtained in systems in vitro and the demonstration of in vivo
      AA is necessary. These findings could be useful in the treatment of some forms of
      PD and should be considered when arranging new mouthrinse formulations.

PMID- 12060432
TI  - Exostosis following a free gingival graft.
AB  - BACKGROUND: There have been few cases reported of exostoses following a free
      gingival graft. In 1980, a free gingival graft was placed on the facial level of
      33-34, developing over the years a significant enlargement. In 1999, since the
      patient felt progressively uncomfortable with the enlarged area, its surgical
      reduction was proposed. METHOD: Under local anesthesia, the hard tissue developed
      under the previously-grafted area, was significantly reduced. The specimen,
      together with a fragment of the covering soft tissue, was sent for histological
      analysis. RESULTS: The surgical wound healed uneventfully, and the patient was
      satisfied with the results. The histology showed the presence of mature bone
      surrounded by a dense connective tissue, whereas the gingival tissue showed
      acanthosis and fibrosis. CONCLUSION: The development of exostoses following a
      free gingival graft can be considered an unpredictable, albeit infrequent side
      effect of this procedure. The fact that most of these exostoses appear in the
      cuspid-premolar area, deserves further consideration.

PMID- 12060431
TI  - Coronary heart disease and periodontitis -- a case control study in Chilean
      adults.
AB  - OBJECTIVES: To investigate the association between periodontal disease parameters
      and coronary ischemic disease among 30-50-year-old Chileans. MATERIAL AND
      METHODS: Cases were 30-50-year-olds who were hospitalized in one of four
      Cardiologic Units in Santiago, Chile, for acute myocardial infarction, unstable
      angina or angina pectoris. Controls had undergone surgery due to gall bladder
      stones or abdominal hernia. Information on blood pressure, serum cholesterol,
      body weight and height, age, occupation, smoking, diabetes and use of
      antidepressants was obtained. A total of 86 persons participated based on
      informed consent, but the analysis is based on 61 persons, for whom a complete
      set of data was obtained. Cases and controls were given a clinical periodontal
      examination comprising assessment of number of teeth present, periodontal pocket
      depth and clinical attachment level at six sites per tooth. The association
      between mean attachment level; mean pocket probing depth; number of teeth present
      and case status was analyzed by conditional logistic regression controlling for
      known risk factors for CHD. RESULTS: The mean attachment level was positively
      associated with case status (OR = 3.17; 95% CI = [1.31; 7.65]), as was the mean
      pocket depth (OR = 8.64; 95% CI = [1.22; 61.20]). The number of teeth present was
      not statistically significantly associated with case status (OR = 0.93; 95% CI =
      [0.83; 1.04]). CONCLUSION: The results are in accordance with those of several
      previous reports. If the results reflect a causal link between periodontal
      diseases and CHD they emphasize the need for better control of periodontal
      diseases. If the associations are-non-causal, they still demonstrate that CHD and
      periodontal diseases cluster in the same sections of the population, which is
      important from a public health point of view.

PMID- 12060433
TI  - Holmium laser enucleation for large (greater than 100 mL) prostate glands.
AB  - BACKGROUND: To evaluate the holmium laser enucleation of the prostate (HoLEP)
      using the transurethral soft tissue morcellator (TUSTM), as a primary surgical
      treatment for symptomatic benign prostatic hyperplasia (BPH) with prostate glands
      > 100 mL. METHODS: Eighteen patients with preoperative prostate volumes > 100 mL
      underwent the HoLEP procedure. The criteria for surgery were determined by a
      preoperative International Prostate Symptom Score (IPSS), a prior failure of
      medical therapy, and urinary retention. RESULTS: The mean preoperative IPSS and
      prostate gland size were 13.8 and 142.3 mL, respectively. The total energy used
      by the laser was 288.4 kJ. The mean catheter time was 23.8 h and,
      perioperatively, no patients had electrolyte abnormalities or required blood
      transfusions. The 3-week postoperative IPSS was 2.8, with minimum long-term
      complications. CONCLUSIONS: Holmium laser enucleation of the prostate with TUSTM
      is a safe and effective alternative to open prostatic surgery for glands > 100
      mL.

PMID- 12060434
TI  - Usefulness of PSA screening in outpatients with bladder cancer: preliminary
      results.
AB  - BACKGROUND: We performed prostate-specific antigen (PSA) screening and evaluated
      its usefulness in outpatients with bladder cancer who may have an elevated risk
      for prostate cancer. METHODS: Sixty-one new or followed-up outpatients with
      bladder cancer were examined between September 1999 and December 2000 in the
      Department of Urology, Gunma University Hospital, Japan. PSA was measured after
      informed consent was obtained, and patients in whom the PSA level was 4.1 ng/mL
      or higher were selected for thorough examination. In the examination, one
      examiner performed DRE (digital rectal examination) and, based on DRE and TRUS
      (transrectal ultrasonography) findings, determined whether prostate biopsy was
      indicated. RESULTS: The average age of the 61 cases was 69.1 +/- 8.6 years, and
      the average PSA level was 3.5 +/- 5.8 ng/mL. The PSA level was 4.1 ng/mL or
      higher in 11 (18.0%) patients, nine of whom underwent six-sextant biopsy under
      TRUS guidance. Of these nine cases, four (6.6%) were diagnosed as having prostate
      cancer. The Gleason score was 7 in three cases and 9 in one case. The clinical
      stage was T2N0M0 in three cases and T3N0M0 in one case. CONCLUSIONS: On PSA
      screening in patients with bladder cancer and patients with a history of
      transurethral resection of the bladder tumor (TUR-BT), prostate cancer was found
      in 6.6%. This rate is higher than in the general population. These cancers were
      classified into intermediate to high-risk groups, and the prognosis of prostate
      cancers could be more important than those of the bladder cancers in two cases
      (50%). We conclude that PSA screening for inpatients with bladder cancer may be
      useful.

PMID- 12060437
TI  - Fate of tetraplegic patients managed by ileal conduit for urinary control: long
      term follow-up.
AB  - BACKGROUND: A study was conducted to evaluate our experience of ileal-conduit
      formation in tetraplegic patients with special reference to late complications
      due to upper urinary tract stones and pyocystis. METHODS: Ileal-conduit formation
      was performed in 16 patients with tetraplegia to improve urinary management. The
      mean age at operation was 46 years (range 19-70) and the mean follow-up period
      was 8.7 years (range 2-17). We evaluated the results retrospectively from
      patients' medical records. RESULTS: Two patients died 2 years after the procedure
      and one patient died 8 years after the ileal-conduit formation. Five patients
      suffered from repeated renal or ureteral stone. In three of these cases, serious
      urinary tract infections developed whenever the stone caused an obstruction.
      Three patients received a cystectomy at the time of the ileal-conduit formation.
      Eight patients suffered from empyema of the bladder and in two of these cases a
      subsequent cystectomy was required. CONCLUSIONS: Ileal-conduit formation should
      be cautiously considered as an option in the urinary management of tetraplegic
      patients, particularly when more conservative management strategies have proved
      unsuccessful. However, an antirefluxing mechanism for the ileal conduit may be
      necessary, and a simultaneous cystectomy may improve the results.

PMID- 12060436
TI  - Tolterodine: as effective but better tolerated than oxybutynin in Asian patients
      with symptoms of overactive bladder.
AB  - BACKGROUND: This double-blind, multicenter study compared the efficacy and
      tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin
      (Alza, Palo Alto, USA) in Asian patients with overactive bladder. METHODS: Two
      hundred-and-twenty-eight adults with overactive bladder symptoms were randomized
      to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n
      = 116). After 8 weeks' treatment, changes in micturition diary variables,
      patients' perception of treatment benefit, and tolerability endpoints were
      determined. RESULTS: The mean (+/- SD) number of micturitions/24 h decreased by
      2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both
      P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased
      by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the
      oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment
      benefit was over 70% in each treatment group. Adverse events were significantly
      lower in the tolterodine group compared with oxybutynin-treated patients (55% vs
      82%; P = 0.001). Dry mouth was reported by significantly fewer patients on
      tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due
      to adverse events were lower in the tolterodine group than with those treated
      with oxybutynin (10% vs 16%). There were no safety concerns. CONCLUSIONS:
      Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the
      treatment of Asian patients with overactive bladder, and shows significantly
      better tolerability. This may enhance compliance during long-term treatment.

PMID- 12060438
TI  - Accuracy of transrectal ultrasound guided prostate biopsy: histopathological
      correlation to matched prostatectomy specimens.
AB  - BACKGROUND: The Gleason grading system is currently the world's most commonly
      used histological system for prostate cancer. It provides significant information
      about the prognosis. Therefore, Gleason score is accepted as an important factor
      in therapeutic decision-making for prostate cancer. This retrospective study
      assessed the correlation of transrectal ultrasound (TRUS) guided biopsy and
      radical prostatectomy specimens in terms of Gleason scores. METHODS: We reviewed
      the records of 103 patients who underwent radical prostatectomy due to clinically
      localized prostate cancer. The Gleason scores of the TRUS biopsies were compared
      with the respective Gleason scores of surgical specimen. RESULTS: In 28.7% of
      cases, the TRUS biopsy score was the same as that of the radical prostatectomy
      specimen. The most significant discordance was the upgrading of well
      differentiated tumors after surgery in 71.7% of cases. However, in 81.8% of cases
      with high Gleason score on TRUS, biopsy was correlated with poorly differentiated
      tumor after surgery. CONCLUSIONS: Well-differentiated tumors on TRUS biopsy did
      not correlate with the grades of final pathology in the majority of cases;
      however, a high Gleason score on TRUS biopsy usually indicated a poorly
      differentiated tumor on prostatectomy specimen. Therefore, the treatment
      algorithms for particularly well-differentiated tumors should not be deduced from
      biopsy histology alone.

PMID- 12060439
TI  - Adenovirus-mediated suicide-gene therapy in an orthotopic murine bladder tumor
      model.
AB  - BACKGROUND: Patients with high-grade transitional-cell carcinoma (TCC) of the
      bladder frequently experience recurrence and progress and have a low response
      rate to chemotherapy in metastatic TCC. In this study, we evaluated the
      feasibility and long-term efficacy of suicide-gene therapy using adenovirus (Ad)
      mediated herpes simplex virus thymidine kinase gene (HSV-TK) and prodrug
      ganciclovir (GCV) as a potential therapeutic approach in murine-orthotopic models
      of TCC. METHODS: A replication defective adenoviral vectors containing toxic HSV
      TK gene under the transcriptional control of RSV (Rous sarcoma virus) promoter
      (Ad-RSV-TK) was used. Orthotopic bladder TCC was established with 1 x 106 murine
      (MBT-2) TCC cells in syngenic C3H/He female mice. Intratumoral injection of Ad
      RSV-TK in combination with GCV (20 mg/kg body weight/day i.p. b.i.d. x 7 days)
      was administered in vivo for the determination of treatment efficacy and long
      term host survival in separate controlled experiments. RESULTS: In vivo
      experiments demonstrated greater than three-fold reductions in MBT-2 tumor growth
      for the animals treated with Ad-RSV-TK (5 x 108 plaque forming units (pfu)/GCV
      therapy (P < 0.01)). Central tumor necrosis and apoptosis were revealed by
      histomorphology and immunohistochemistry compared with other control animals (non
      treated, GCV alone, Ad-RSV-TK alone). Direct intratumoral injection with Ad-RSV
      TK/GCV also resulted in significantly improved survival over the control groups
      in separated experiment (log-rank test, P < 0.05). CONCLUSIONS: Suicide-gene
      therapy using Ad-RSV-TK/GCV provides an effective therapy in an experimental
      murine orthotopic bladder cancer by significantly inhibiting tumor growth and
      improving long-term host survival.

PMID- 12060440
TI  - Primary malignant melanoma of the male urethra.
AB  - We report a case of primary malignant melanoma of the male urethra in a patient
      whose penile shaft was successfully preserved, but who proceeded to acute renal
      failure (ARF) after interferon (IFN)-beta adjuvant immunotherapy. Primary
      malignant melanoma of the male urethra is rare and usually shows highly malignant
      potential. Therefore, urologists must often perform phallectomy, which impacts on
      the patient both sexually and mentally. A 64-year-old man presented at Saiseikai
      Sendai Hospital with asymptomatic gross hematuria and was diagnosed as distal
      urethral tumor. We predicted the highly malignant potential of this tumor from
      the urethroscopic finding and from urinary cytological examination. We did not
      select trans-urethral resection (TUR), but selected partial urethrectomy. This
      patient proceeded to ARF 1 month after natural IFN-beta treatment as an adjuvant
      immunotherapy. As IFN-beta rarely induces the delayed renal failure, urologists
      should be aware of renal dysfunction after IFN-beta therapy for the treatment of
      malignant melanoma.

PMID- 12060442
TI  - Metastatic urothelial cancer showing an efficacy by low-dose cisplatin.
AB  - A 69-year-old man who had developed multiple distant metastases on retrocaval
      lymph nodes after four courses of Methotraxate, Vinblastine, Adriamycin,
      Cisplatin (MVAC) chemotherapy was successfully treated by intravenous infusion of
      low-dose cisplatin (CDDP) (10 mg/time, once per week) and oral administration of
      600 mg/day 5'-deoxy-5-fluorouridine (5'-DFUR), a pro-drug of 5-FU, in an
      outpatient setting. A partial response (62% reduction rate) was confirmed by
      abdominal computed tomography (CT) scan after 7 months. Although the CDDP dosage
      had been reduced to 5 mg/week 1 year previously, the tumor was still reducing in
      size in November 2000. Combination therapy of 5'-DFUR with low-dose CDDP could
      become an option for advanced bladder cancer that compromises the patient's
      quality of life, especially when used in an outpatient setting.

PMID- 12060443
TI  - Cervical cancer should be considered as a rare complication of oncogenic HPV
      infection rather than a STD.

PMID- 12060444
TI  - Stage I-II endometrial adenocarcinoma evolution of therapeutic paradigms: the
      role of surgery and adjuvant radiation.
AB  - The objective was to review the English-language literature regarding the utility
      of adjuvant radiation therapy following surgery for endometrial adenocarcinoma.
      An OVID software (Ovid Technologies, Inc., New York, NY) search of Medline
      articles from 1975 to 2001 was conducted using the keywords "endometrial
      neoplasm," "surgery," and "radiation therapy." The papers were assessed with
      regard to (a) extent of surgical staging (b) type of adjuvant radiotherapy
      utilized: external vs. brachytherapy vs. combination therapy; and (c) whether the
      patients were treated as part of prospective trial or reported as a descriptive
      series reflecting an institution's practice pattern. Survival rates are excellent
      for patients with early stage disease treated in either paradigm of extended
      surgical staging with more restricted use of the adjuvant therapy or simple
      hysterectomy bilateral salpingoophorectomy with more frequent use of adjuvant
      radiotherapy. All three prospective-randomized trials (PRCT) have shown an
      improvement in local control but no overall survival benefit for the entire
      accrued group. All three PRCTs have shown a higher risk of disease recurrence in
      older patients or those with grade 3 histology or deep invasion. Each suggests
      there may be a survival benefit for the subset of patients with such high-risk
      features, but at present there is no prospective data that demonstrates adjuvant
      radiotherapy will improve the overall survival for the highest-risk subset of
      older patients with high-grade deeply invasive disease.

PMID- 12060445
TI  - Local radiation therapy for localized relapsed or refractory ovarian cancer
      patients with or without symptoms after chemotherapy.
AB  - The purpose of this paper is to prospectively evaluate the effects of local
      radiation therapy upon localized ovarian cancer following chemotherapy. Patients
      with objective relapses or refractory disease but with localized epithelial
      ovarian cancers and who had undergone at least one regimen of chemotherapy were
      enrolled in this study. External irradiation was performed on all patients.
      Twenty patients, with a mean age of 53.8 +/- 10.3 y, were enrolled in this study.
      The median number of previous chemotherapies was 2. The interval between previous
      chemotherapy and radiation therapy was 4.5 months. The maximum diameter of the
      lesions was 3.6 +/- 1.8 cm. The irradiation dose was 52.3 +/- 8.3 Gy. Neither
      hematologic nor intestinal toxicity >grade 3 was observed. Forty-four disease
      sites, including the lymph nodes, vaginal cuff, pelvis, abdomen, subcutaneous
      regions, and the brain were irradiated. Thirty of these sites were symptom-free
      before irradiation. In patients with symptoms, the symptomatic relief was
      obtained in approximately 50% of patients. Smaller lesions (P = 0.024) and lymph
      nodes (P = 0.042) demonstrated better responses than larger lesions or other
      sites, respectively. Regression rates correlated with longer survivals (P =
      0.0195) after radiation therapy. Survival was significantly better when radiation
      therapy was given before patients had symptoms (P = 0.001). Survival was also
      better in patients with lymph node disease only (P = 0.0069). We conclude that
      local radiation therapy may be one of the treatment options for relapsed or
      refractory but localized ovarian cancer, particularly when the tumor is small
      and/or located in the lymph nodes, even when patients had no symptoms.

PMID- 12060446
TI  - Risk factors for endometrial hyperplasia: results from a case-control study.
AB  - We analyzed epidemiologic characteristics of women at risk for endometrial
      hyperplasia (EH), using data from a case-control study. One hundred twenty nine
      women aged 35-73 (median 51 years) with histologically confirmed complex
      endometrial hyperplasia without atypies identified at the University of Milan
      during the period 1990-99 were examined. Controls were 258 non hysterectomized
      women aged 36-74 (median 52 years), admitted to a network of hospitals covering
      the same area where cases had been identified for conditions other than
      gynecological, malignant, or hormone-related. Cases with EH were more educated
      than controls (OR > 12 years of education vs. < 7: 2.8, 95% CI 1.7-4.8), more
      frequently obese (OR 2.7, 95% CI 1.5-5.0) and diabetic (OR 2.4, 95% CI 0.8-6.9).
      Parous women (OR 1.8) and women reporting induced abortions (OR 1.6) showed an
      increased risk of EH, but the associations were not statistically significant.
      Compared to premenopausal women, the OR of EH was 0.2 (95% 0.1-0.5) for
      postmenopausal ones. Compared to women reporting menopause at age 50 or less, the
      OR of endometrial hyperplasia was 1.5 (95% CI 0.6-3.5) and 2.2 (95%CI 0.7-6.7),
      respectively, in women with menopause at age 50-52 and > or = 53. Considering
      postmenopausal women only the OR was 3.1 (95% CI 1.1-9.3) for use of hormonal
      replacement therapy (HRT). We conclude that this study indicates that high
      education, obesity, diabetes, and HRT use increase the risk of endometrial
      hyperplasia.

PMID- 12060447
TI  - Early detection of endometrial cancer by combined use of vaginal ultrasound and
      endometrial vacuum sampling.
AB  - With increasing lifespan and decreased incidence of uterine cervical cancer, the
      importance of the proper and early diagnosis of endometrial cancer has become a
      demand to gynecology. The objective of the present study is to evaluate the
      effectiveness of gynecologic diagnostic tools in detection of endometrial cancer
      in early stage. The patients (72) involved in the study, after giving their
      informed consent, were investigated by transvaginal ultrasound and subsequent
      vacuum endometrial sampling in office settings. Whenever the histology
      examination of endometrial vacuum sampling showed hyperplasia or carcinoma, it
      was reassured by sampling with dilatation and curettage. The analysis of
      sonography and histology results showed that in 4 cases (5.6%) endometrial
      hyperplasia and in two cases (2.8%) endometrial adenocarcinoma were present. Also
      analyzed were sensitivity, specificity, positive and negative predictive values
      for histology results and for sonographic findings. These results show that
      transvaginal ultrasound is a reliable method for screening for endometrial
      carcinoma. Moreover, in the case of pathologic endometrial change suspected by
      ultrasound, the combination of vacuum endometrial sampling with ultrasound
      examination can yield firm diagnosis in office settings, saving cost and time in
      early diagnosis of endometrial cancer.

PMID- 12060448
TI  - The prognostic importance of p53, bcl-2, and bax in early stage epithelial
      ovarian carcinoma treated with adjuvant chemotherapy.
AB  - Epithelial ovarian cancer is one of the major causes of death among women. The
      increasing knowledge about molecular events involved in the early stages of
      ovarian tumorigenesis may provide the basis for management in the future. In a
      series of 109 patients with epithelial carcinomas in FIGO stages IA-IIC, a number
      of clinicopathologic prognostic factors (age, FIGO stage, histopathologic type,
      and tumor grade) were studied in relation to the biologic factors p53, bcl-2, and
      bax, which are important regulators of apoptosis. Immunohistochemical techniques
      were used. All the patients received adjuvant chemotherapy after the primary
      surgery. Univariate analysis showed that expression of p53 was significantly
      associated with tumor grade (P = 0.014), probability of persistent disease (P =
      0.016), and cancer-specific survival rate (P = 0.007). Positive bcl-2 staining
      was associated with endometrioid tumor subtype (P = 0.029) and a favorable tumor
      grade distribution (P = 0.034), but not with the survival status. The combined
      p53-bcl-2 expression was related to histopathologic subtype (P = 0.032), tumor
      grade (P = 0.011), persistent disease (P = 0.014), and risk of dying due to the
      disease (P = 0.039). The bax status was not a prognostic factor, but the combined
      p53-bax expression showed an association with FIGO stage (P = 0.014), tumor grade
      (P = 0.034), persistent disease (P = 0.006), and risk of dying due to the disease
      (P = 0.039). The combined bcl-2-bax expression was related to histopathologic
      subtype (P = 0.045) and tumor grade (P = 0.022). In a multivariate Cox analysis,
      tumor grade (P = 0.014), and p53 status (P = 0.020) were independent and
      significant prognostic factors with regard to the cancer-specific survival rate.

PMID- 12060449
TI  - Immature glandular features in squamous cell carcinoma of the uterine cervix as
      an independent indicator of resistance to radiotherapy.
AB  - The aim of this study was to evaluate the significance of "immature glandular
      features" in cervical squamous cell carcinoma (SCC) as an indicator of tumor
      radioresistance. Pretreatment biopsied tissue specimens of cervical SCC from 100
      patients who were uniformly treated with radiotherapy alone were classified into
      clinically radioresistant (cR) and radiosensitive (cS) groups. Seven histologic
      parameters comprising glassy cells, signet ring cells, squamous differentiation,
      recognizable gland, nuclear atypia, stromal response, and mitotic counts were
      examined. Glassy cells and signet ring cells were regarded as "immature glandular
      features". The correlation of these seven parameters with tumor response to
      radiotherapy and patient prognosis was analyzed by univariate and multivariate
      analyses. As objective indicators of glandular differentiation, alcian-blue
      staining and immunostaining of cytokeratins 7 and 20 were also performed. It was
      revealed that immature glandular features, absence of squamous differentiation,
      and low nuclear atypia were significant indicators of radioresistance of the
      tumor and of poorer patient prognosis. Combining those histological parameters,
      the present SCC cases were classified into 26 pathologically radioresistant (pR)
      and 74 radiosensitive (pS) groups. In the pR group, 54% (14 of 26) were
      clinically radioresistant, whereas 20% (15 of 74) of the pS group were clinically
      radioresistant (P = 0.002). The overall prognosis of the pR group was much poorer
      than that of the pS group (P < 0.0001). This correlation also held true in cases
      of identical stage and age. We could not show objectively glandular
      differentiation of "immature glandular features". Nonetheless, the identification
      of "immature glandular features" was effective in predicting the radiotherapy
      resistance of cervical SCC and poorer patient prognosis.

PMID- 12060450
TI  - Immunohistochemical evaluation is not prognostic for recurrence in fully staged
      high-risk endometrial cancer.
AB  - The objective of this study was to determine the prognostic significance of
      common immunohistochemical pathologic risk factors in fully staged high-risk
      endometrial cancers. Sixty-two of 265 consecutive endometrioid adenocarcinomas
      were considered high risk for recurrence because of deep myometrial invasion and
      poor differentiation (stage IC, G3), cervical metastasis (stage II), ovarian
      metastasis (stage IIIA) or lymph node metastasis (stage IIIC). All patients
      underwent complete surgical staging with bilateral pelvic and aortic
      lymphadenectomy. Expression of estrogen receptors, progesterone receptors, p53,
      HER-2/neu, c-myc, bcl-2, FVIII, and Ki-67 were analyzed by immunohistochemistry
      using commercially available monoclonal antibodies. A general linear model
      multiple regression analysis was used to determine if any of the immunostains,
      along with grade or stage, were predictors of recurrence. Mean age was 68 years
      and mean weight 188 pounds. Sixty-eight percent of patients had associated
      medical illness. The majority of tumors were poorly differentiated (44%) and were
      stage IIIC (29%). Mean follow-up was 4.3 years. Fourteen patients (22%) developed
      tumor recurrence. Using multiple regression analysis, none of the immunostains
      were predictive for recurrence (P = 0.19-.96). Only stage and grade were
      predictive of tumor recurrence (P = 0.04,.02). We conclude that in completely
      staged high risk endometrial cancer, commonly used immunohistochemical risk
      factors are not predictive for recurrence.

PMID- 12060451
TI  - Immunohistochemical expression of p53, bcl-2, and p21(WAF1/CIP1) in early
      cervical carcinoma: correlation with clinical outcome.
AB  - The objective of this study was to assess the value of p53, bcl-2, and
      p21(WAF1/CIP1) immunoreactivity as predictors of pelvic lymph node metastases
      (LNM), recurrences, and death due to the disease in early stage (FIGO I-II)
      cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were
      also evaluated in this series of patients treated by radical hysterectomy
      (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A
      tumor was regarded as positive when more than 30% of the neoplastic cells
      exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in
      43.5% for bcl-2, and in 25.0% for p21(WAF1/CIP1). None of them was able to
      predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death
      from disease were significantly associated with the FIGO stage (P = 0.014, P =
      0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was
      91.6% and the overall survival rate was 90.5%. It was concluded that
      immunohistochemically detected p53, bcl-2, and p21(WAF1/CIP1) appeared to be of
      no predictive value with regard to LNM, tumor recurrences, or long-term survival
      in early cervical carcinomas.

PMID- 12060452
TI  - P53 expression as a predictor of recurrence in cervical squamous cell carcinoma.
AB  - P53 protein function is frequently down-regulated in cervical cancer by
      complexing with human papillomavirus (HPV) E6 protein, leading to degradation of
      p53, genomic instability, and mutations. Results are controversial, however, on
      the prognostic value of p53 protein expression in cervical cancer. In this study,
      a cohort of 220 Brazilian women with FIGO stage IB-III cervical squamous cell
      carcinoma (SCC), followed for 5 years, was analyzed for p53 protein expression
      using immunohistochemistry. The disease-free survival (DFS) and relapse rate were
      analyzed using univariate (Kaplan-Meier) and multivariable (Cox's proportional
      hazards model) survival analyses. P53 protein expression was detected in 35% of
      the patients, including 21% in stage I, 28% in stage II and 51% in stage III of
      disease. Of 220 women, only 116 completed one of the treatment options
      standardized by FIGO within 120 days. There was a higher risk of relapse in stage
      II and III disease, that was not modified by p53 positivity; HR 3.0 (1.3-6.5) to
      stage II and HR 4.0 (1.9-8.5) to stage III. The multivariate analysis evidenced
      that p53 expression is not an independent factor exceeding the power of FIGO
      stage as the single most important determinant of the hazards for disease
      relapse.

PMID- 12060453
TI  - Low-dose mitomycin C, etoposide, and cisplatin for invasive vulvar Paget's
      disease.
AB  - We report the effect of low-dose mitomycin C, etoposide, and cisplatin (low-dose
      MEP) therapy for three patients with invasive vulvar Paget's disease (invasive
      VPD) who declined radical vulvectomy and skin grafting. One patient achieved a
      complete response, while the other two showed partial responses (PR) without
      grade 3 or 4 adverse effects. The two patients with PR were undergone partial
      vulvectomy and inguinal lymph node dissection. All patients have no sign of
      recurrence for 10 months after chemotherapy. Our present results suggest that low
      dose MEP is an effective and safe chemotherapy for invasive VPD and low-dose MEP
      may significantly improve postoperative quality of life in patients with invasive
      VPD by avoiding extensive vulvar resection and skin grafting.

PMID- 12060454
TI  - Cervical implant from villoglandular endometrial adenocarcinoma masquerading as
      cervical villoglandular adenocarcinoma.
AB  - This is an unusual presentation of a rare subtype of endometrial adenocarcinoma
      (villoglandular papillary carcinoma, VGPC) in a 71-year-old woman, which was
      initially diagnosed on cervical biopsy as being primary cervical VGPC. Loop
      excision failed to show any evidence of residual disease. Subsequent hysterectomy
      revealed a localized villoglandular carcinoma involving the uterine fundus and
      invading the inner one-third of the myometrium, the background endometrium was
      atrophic. The remaining cervix contained a focus of papillary forming endometrial
      type adenocarcinoma involving the surface epithelium and the superficial
      subepithelial glands. In conclusion, VGPC of cervix occurs mainly in young women
      and can be treated conservatively, pathologists should be cautious in making such
      a diagnosis in a postmenopausal woman before ruling out a primary endometrial
      origin.

PMID- 12060455
TI  - Mixed choriocarcinoma in a postmenopausal patient.
AB  - Gestational trophoblastic disease rarely presents in patients beyond the
      reproductive years. To our knowledge, this is the first case of mixed
      trophoblastic disease in a postmenopausal woman. We present here a case of a 60
      year-old woman with evidence of a pelvic mass and pulmonary metastasis. Surgery
      revealed an 8 x 6 x 6 cm multinodular uterine tumor involving the right adnexa.
      Histologic review was consistent with choriocarcinoma with intermediate
      trophoblastic features. Postoperative beta-hCG was 381 561 mIU/ml. We conclude
      that maintaining a high index of suspicion facilitates the identification of
      postmenopausal patients with metastatic gestational trophoblastic disease. This
      case reconfirms the deceptive presentation of the "great masquerader".

PMID- 12060456
TI  - Long-term disease-free survival after breast cancer metastatic to the ovary.
AB  - The prognosis of patients with breast cancer symptomatically metastatic to the
      ovary is almost uniformly poor. In this case report, we present a 33-year-old
      para-4 with a symptomatic metastasis to the ovary. Previously, a modified radical
      mastectomy with adjuvant radiotherapy had been performed for invasive ductal
      carcinoma of the left breast. Laparotomy showed a 13-cm tumor of the left ovary;
      frozen section histology showed malignancy consistent with the previous breast
      cancer. The patient received adjuvant combination chemotherapy. About 5 years
      later, a carcinoma of the right breast was treated with conservative surgery and
      adjuvant radiation and chemotherapy. After a further 4 years, a recurrence at the
      left chest wall was treated with radiation. At the last follow-up, more than 13
      years after the first breast cancer and 12 years after the ovarian metastasis,
      the patient was alive and well without evidence of disease. Bilateral
      oophorectomy is a therapeutic option in premenopausal patients with localized or
      advanced breast cancer. Our patient experienced long-term disease-free survival
      following an isolated metastasis to one ovary. This represents the first report
      of long-term survival of such a patient in the literature.

PMID- 12060457
TI  - A nerve-sparing radical hysterectomy: guidelines and feasibility in Western
      patients.

PMID- 12060459
TI  - Humoral rejection and endothelial cell activation, 2001.

PMID- 12060460
TI  - Pig endogenous retroviruses and xenotransplantation.
AB  - Xenotransplantation of porcine organs might provide an unlimited source of donor
      organs to treat endstage organ failure diseases in humans. However, pigs harbour
      retroviruses with unknown pathogenic potential as an integral part of their
      genome. While until recently the risk of interspecies transmission of these
      porcine endogenous retroviruses (PERV) during xenotransplantation has been
      thought to be negligible, several reports on infection of human cells in vitro
      and spread of PERV from transplanted porcine islets in murine model systems have
      somewhat challenged this view. Here, we compile available data on PERV biology
      and diagnostics, and discuss the significance of the results with regard to the
      safety of clinical xenotransplantation.

PMID- 12060461
TI  - Spectrotype analysis and clonal characteristics of human anti-Gal alpha1-3Gal
      antibodies.
AB  - Galalpha1-3Gal (anti-Gal), a polyclonal so-called natural antibody (Ab), is
      present in large amounts in human serum not only as IgG-, but also as IgM- and
      IgA-isotypes. It has gained a particular interest in the context of
      xenotransplantation, because the endothelial pig cells express the terminal
      Galalpha1-3Gal determinant on several adhesion molecules. Little is known of it's
      function and direct examination of the structure of the Ig genes responsible for
      coding anti-Gal is lacking. We used the technique of isoelectric focussing
      (IEF)/affinity immunoblotting for direct analysis of the clonal distribution and
      spectrotype analysis of IgM- and IgG anti-Gal. By single cell analysis of
      magnetic bead and fluorescent-activated cell sorter (FACS) isolated mature anti
      Gal bearing human B cells from whole blood we analyzed the VH gene families
      involved in anti-Gal production. Oligoclonal and individually distinct IgG
      banding patterns were found with isoelectric points between 4 and 9. IgM
      spectrotypes revealed to be more uniform with a polyclonal banding pattern of
      more than 12 bands at a pH between 4.7 and 7. IgG- and IgM-banding patterns over
      a period of 6 months remained unchanged. Single cell polymerase chain reaction
      (PCR), with all family specific primers, revealed the use of the VH2f gene family
      for the IgG2 isoptype. The differences found in the spectrotype banding patterns
      of IgG and IgM could be explained by the suggestion that anti-Gal IgM were
      produced by the use of unmutated germline genes and the possibility of the
      absence of somatic mutations. The greater clonal heterogeneity in the IgG
      population could be explained by somatic hypermutations during the switch from
      IgM to IgG. The use of this VH2f gene family, which is also involved in the
      generation of Abs against bacterial pathogens, could mean that this is a
      predominant region used for the generation of such natural occurring antibodies.

PMID- 12060462
TI  - Lectin interactions with alpha-galactosylated xenoantigens.
AB  - alpha-Galactosylated xenoantigens (Galalpha1-3Galbeta1-4GlcNAcbeta1 and Galalpha1
      3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) are often detected with the alpha-Gal
      specific lectin Griffonia simplicifolia 1 isolectin B4 (GS1 B4). However, this
      lectin exhibits a broad and variable specificity for carbohydrates terminating in
      alpha-Gal. Thus, both false positive and false negative results may occur when
      GS1 B4 is used to determine natural antigens in xeno (pig-to-primate)
      transplantation research. To refine the tools for detecting alpha-galactosylated
      antigens we have studied the binding of various alpha-galactophilic lectins to
      alpha-galactosylated neoglycoproteins. The lectins were: Euonymus europaeus
      agglutinin (EEA), Griffonia simplicifolia 1 isolectin B4 (GS1 B4), Maclura
      pomifera agglutinin (MPA) and Pseudomonas aeruginosa agglutinin (PA-IL). Although
      both GS1 B4 and MPA strongly bound glycoconjugates terminating in Gal there seems
      to be some differentiation in their sugar binding preferences. MPA was the only
      lectin that showed high affinity for the pentasaccharide Galalpha1-3Galbeta1
      4GlcNAcbeta1-3Galbeta1-4Glc and for the Galalpha-glycans on non-primate
      thyroglobulin. The length of the xenoantigenic carbohydrate chain may influence
      the nature of the inhibition when a simple sugar is used to inhibit GS1 B4
      binding to the xenoantigen. Inhibition studies of MPA GS1 B4 interaction further
      suggest that both lectins attach to the same site of the carbohydrate antigen and
      that GS1 B4 in addition binds to at least one other site that has no affinity for
      MPA. When lectins are used for recognition and investigation of natural Galalpha
      antigens, we propose that GS1 B4 and MPA should accompany each other.

PMID- 12060463
TI  - IFN-gamma but not IL-4 is important for mouse CD4+ T cell-mediated macrophage
      activation following their exposure to pig cells in vitro.
AB  - In order to investigate the mechanism by which CD4+ T cells and macrophages
      interact in the xenogeneic immune response, murine CD4+ T cells and macrophages
      were used as responder cells in culture with irradiated fetal pig spleen cells
      (FPSC) as pig xenogeneic stimulators. In this in vitro model, murine CD4+ T cells
      and macrophages were cultured individually, or together with FPSC. In addition,
      mouse CD4+ T cells were also cultured with autologous macrophages which were
      previously stimulated by FPSC. The cultured murine cells were analyzed for
      expression of CD4+ T cell and macrophage activation markers (cell surface markers
      and cytokines) as well as cytokine production. CD4+ T cells and macrophages
      cultured alone or together without FPSC showed unchanged low levels of expression
      of activation markers. Coculture of macrophages with FPSC and in the absence of
      CD4+ T cells induced increased expression levels of all the activation markers
      examined except B7.2 and ICAM-1. Addition of CD4+ T cells to the coculture
      further enhanced this up-regulation. Coculture of CD4+ T cells with FPSC
      stimulated macrophages, but not naive macrophages, or FPSC alone, resulted in
      significantly increased numbers of CD4+ T cells coexpressing their activation
      markers, especially IFN-gamma and CD40L, and this expression was enhanced further
      by including FPSC in the coculture. The activation of both CD4+ T cells and
      macrophages in their coculture with FPSC was suppressed by neutralizing IFN-gamma
      but not IL-4. Our results demonstrated that interaction of CD4+ T cells and
      autologous macrophages was required for their optimal activation in response to
      pig xenogeneic stimulation. The mechanisms involved included cell-cell and/or
      cytokine interactions, and in particular IFN-gamma mediated communication was
      involved. Macrophages activated by pig cells in the absence of CD4+ T cells were
      able to activate naive CD4+ T cells, thus providing an important communication
      pathway between innate immune activation and a T cell mediated response in
      xenograft rejection.

PMID- 12060464
TI  - Porcine mononuclear cells adhere to human fibronectin independently of very late
      antigen-5: implications for donor-specific tolerance induction in
      xenotransplantation.
AB  - To combat the shortage of donor organs, transplantation across species barriers
      has been proposed. Induction of tolerance would overcome the substantial
      immunologic barriers to xenotransplantation and would avoid the chronic use of
      immunosuppressive agents. Successful transplantation of hematopoietic cells
      induces robust specific tolerance to donor antigens in allogeneic and xenogeneic
      models. The beta1 integrin class of adhesion molecules and their interactions
      with extracellular matrix components are thought to be integral to the
      engraftment and maturation of hematopoietic stem cells. We therefore examined the
      efficacy of porcine very late antigen-5 (VLA-5) and VLA-4 interactions with the
      human extracellular matrix (ECM) protein, fibronectin. Peripheral blood
      mononuclear cells (PBMCs) from humans and miniature swine were flourochrome
      labeled and adhesion to plates coated with whole human fibronectin (whFN) or its
      120 KDa fragment containing the VLA-5 binding region was determined. Flow
      cytometry and immuno- precipitation were used to identify a monoclonal antibody
      that cross-reacted on porcine VLA-5. Human and pig PBMC adhesion to human
      fibronectin (hFN) or 120 kDa fragment-coated plates was assessed following
      incubation with control ab, anti-VLA-4, anti-VLA-5, or soluble fibronectin. Using
      rabbit complement, cells expressing VLA-5 were purged from PBMC preparations
      before performing the adhesion assay. Porcine and human PBMC both adhered to hFN
      in a divalent cation-dependent and activation-dependent manner. Adhesion to hFN
      of human but not pig PBMC was blocked by anti-VLA-5 monoclonal antibody SAM-1,
      although this mAb immunoprecipitated a heterodimeric cell surface molecule
      (155/135 kDa) resembling VLA-5 from pig PBMC. Complement-mediated depletion of
      VLA-5-expressing cells ablated specific binding of human but not porcine cells to
      hFN and its 120 kDa fragment. Addition of soluble fibronectin was capable of
      blocking adhesion of PBMC of both species to hFN. Anti-VLA-4 reduced the binding
      of PBMC from both species to hFN to a similar extent. Human and pig cells can
      specifically adhere to hFN and its 120 kDa fragment, suggesting that this
      critical cell-ECM interaction is preserved across species. While human cells
      exclusively use VLA-5 for binding to the 120 kDa fragment, porcine cells could
      not be shown to adhere to whFN or its 120 kDa fragment via VLA-5. However,
      porcine VLA-4 is capable of mediating adhesion to human FN. We conclude that
      disparities in the adhesive interactions of beta1 integrins may be a barrier to
      the use of porcine hematopoietic stem cell transplantation as a means of inducing
      donor-specific tolerance in the pig to human species combination.

PMID- 12060465
TI  - Reduction of alpha-galactosyl xenoantigen by expression of endo-beta
      galactosidase C in pig endothelial cells.
AB  - BACKGROUND: Elimination of the Galalpha1-3Galbeta1-4GlcNAc (alphaGal) epitope has
      been considered to be essential for successful pig-to-human xenotransplantation
      but, unfortunately, has not been achieved. Endo-beta-galactosidase C (EndoGalC)
      is an endoglycosidase which cleaves the Galbeta1-4GlcNAc linkage in the alphaGal
      epitope and digests out the Galalpha1-3Gal disaccharide. Because of its potent
      activity in physiological pH conditions, EndoGalC can remove alphaGal epitopes
      expressed on the cell surface of pig erythrocytes and vascular endothelial cells
      almost completely. In vivo or ex vivo administration of EndoGalC successfully
      reduced alphaGal expression in pig kidneys to an undetectable level, but alphaGal
      epitopes soon reappeared. Gene expression of EndoGalC in pig cells was attempted
      to solve this problem. As the terminal alphaGal is transferred in the trans-Golgi
      network by alpha-1,3-galactosyltransferase (alpha1,3GT), colocalization of the
      EndoGalC gene with the alpha1,3GT gene was expected to be one of the most
      reliable ways to eliminate the alphaGal epitope. METHODS AND RESULTS: The
      sequence of pig alpha1,3GT, including the cytoplasmic tail, transmembrane domain
      and stem region, was ligated upstream of EndoGalC, and the conjugated gene was
      expressed in pig aortic endothelial cells and COS7 cells. Following the
      introduction of the gene, the alphaGal epitope on pig aortic endothelial cells
      was effectively reduced. Transfection studies in COS7 cells using EndoGalC
      combined with alpha1,3GT showed that the expressed EndoGalC was localized not
      only inside, but also outside, the cells. The expression of EndoGalC conjugated
      with a murine immunoglobulin (Igkappa)-chain signal sequence also showed a
      similar effect. CONCLUSIONS: These results suggest the effectiveness of gene
      transfer with EndoGalC into pig endothelial cells, and strongly encourage us to
      produce transgenic animals with the expressed enzyme.

PMID- 12060466
TI  - Differential expression of Galalpha1,3Gal epitopes on fetal and adult porcine
      hematopoietic cells.
AB  - Galalpha1-3Gal (Gal) is the major epitope on pig tissues bound by human natural
      antibodies. Xenogeneic hematopoietic cell transplantation is being investigated
      to induce immunological tolerance to xenografts. We have investigated the level
      of Gal expression on pig hematopoietic cells. Cells were collected from pig fetal
      liver and bone marrow (BM), and also from adult BM and peripheral blood, before
      and after treatment with pig-specific hematopoietic growth factors. Fluorescent
      activated cell sorting (FACS) analysis was performed with the M86 monoclonal
      antibody (specific for Gal), lineage markers, and biotinylated stem cell factor
      (SCF) to detect c-kit expression. In fetal pig BM and liver, there was no
      significant difference in Gal expression between monocytes/macrophages (myeloid
      cells) and lymphocytes. In adult hematopoietic cells from all sources, Gal
      positive subpopulations in T cells showed weak expression of Gal, whereas B cells
      demonstrated higher expression, and myeloid cells showed highest expression.
      Adult BM and mobilized peripheral blood progenitor cells contained small
      populations with very low or negligible expression of Gal. A very small
      population of c-kit-positive cells, indicating progenitor cells, were Gal
      negative. The small Gal-negative population that exists in progenitor cells might
      explain why some pig colony forming units (CFU) can be resistant to human serum.

PMID- 12060468
TI  - Instrumental quantification and its clinical application in the future.

PMID- 12060469
TI  - Utilization of a high-resolution digital imaging system for the objective and
      quantitative assessment of hyperpigmented spots on the face.
AB  - BACKGROUND/AIMS: The aim of this study was to quantify and confirm the efficacy
      of cosmetic formulations for hyperpigmented spots over a wide area of the face
      using a high quality digital imaging system that we developed. METHODS: A total
      of 120 Japanese female volunteers aged 25-60 years with solar lentigines were
      treated for 6 months with a skin lightening moisturizer (SLM, thereafter)
      containing 3% magnesium ascorbyl phosphate on one side of the face and vehicle on
      the other side. During the course of the study, facial images were collected by
      the image analysis to measure facial skin colour and the total area of
      hyperpigmented spots. The evaluation was also conducted by visual grading.
      Measurements were made before and 1, 3, and 6 months after starting the
      application, and again 6 months after discontinuing the treatment. Three similar
      clinical studies using the same protocol were repeated for up to one-month to
      confirm the reproducibility of the results and to examine seasonal variation.
      RESULTS: SLM significantly reduced the total area of hyperpigmented spots (P <
      0.005) after one month of treatment compared to the vehicle, with no significant
      variation in facial skin colour tone in the areas outside the hyperpigmented
      spots. The results of the visual grading were consistent with those obtained by
      image analysis. The total area of hyperpigmented spots 6 months after
      discontinuing the treatment had returned to pre-treatment levels. The
      reproducibility of these clinical results was demonstrated in three follow-up
      studies. CONCLUSIONS: A high-resolution digital imaging method, combined with a
      split-face clinical protocol is sensitive enough to prove that SLM readily
      reduces hyperpigmented spots, while maintaining normal facial skin colour.

PMID- 12060470
TI  - Graphic analysis of the relationship between skin colour change and variations in
      the amounts of melanin and haemoglobin.
AB  - BACKGROUND/AIMS: The L*a*b* coordinate is the most commonly used colour system to
      measure skin colour in dermatology and cosmetology. In this system, a* and L* are
      often used for quantification of the degrees of erythema and pigmentation. The
      aim of this study was to examine whether a* and L* can be used as specific scales
      to indicate the amount of haemoglobin and melanin, respectively, in the skin.
      METHODS: The a* and L* values were examined with a reflectance spectrometer in
      various skin conditions or lesions caused by a change in the amount of either
      melanin or haemoglobin, i.e. vitiligo, ultraviolet-induced pigmentation (PG),
      erythema resulting from slapping (ER), corticosteroid-induced blanching, erythema
      due to stasis by arm lowering, and a combination of PG and ER. The differences in
      values between the test sites and the adjacent normal skin, deltaa* and deltaL*,
      were plotted on the deltaa*-deltaL* plane and analysed statistically and
      geometrically. RESULTS: L* depended substantially not only on melanin but also on
      haemoglobin, especially if the oxygen saturation level was expected to be low. a*
      was also influenced by melanin. The results of graphic analysis indicated that a
      linear transformation of (deltaa*, deltaL*) into (deltaHb = 1.68 deltaa* + 0.60
      deltaL*, deltaMel =-1.06 deltaa*-1.44 deltaL*) was suitable for separately
      estimating the change in the amount of haemoglobin (deltaHb) and in that of
      melanin (deltaMel). CONCLUSION: The results of this study may be of value for
      understanding the relationship between colour coordinates of the skin and the
      quantities of haemoglobin and melanin, and may be of use when pigmented lesions
      of the face are monitored by tristimulus colourimetry, as facial skin colour is
      affected considerably by the rich and easily variable cutaneous blood flow.

PMID- 12060471
TI  - Quantification of erythema using digital camera and computer-based colour image
      analysis: a multicentre study.
AB  - BACKGROUND/PURPOSE: Colour measurements obtained from digitized images have been
      proposed as a simple and cost-effective way to evaluate skin colour and the
      activity of treatments. The main disadvantage of the method is the fact that it
      is highly dependent on ambient light: even if an accurate control of subjects'
      illumination is provided, readings remain not comparable among different
      laboratories. The purpose of this study was to develop a highly reproducible
      system for computerized colour image analysis of skin erythema, making it
      possible to compare readings from different environmental light conditions.
      PATIENTS AND METHODS: Three hundred and forty-eight Caucasian adult healthy
      subjects (age range: 18-60 years) of both sexes (14% males, 86% females), were
      enrolled in the study by 49 dermatologists distributed all over Italy. They were
      recruited among patients who required aesthetic treatments involving skin
      erythema, like chemical peeling and laser epilation. Once the treatment was
      administered, clinical evaluations and pictures were taken at the level of
      treated areas. Visual assessment of erythema was done on the basis of
      conventional clinical grades (0 = absent; 1 = slight; 2 = moderate; 3 = intense).
      The clinicians participating in the study were asked to put a standard colour
      marker (red, green and blue coloured self-adhesive ring) in the photographed skin
      area. The difference between r, g, b values of photographed colour markers on the
      skin of single patients participating in the study and the r, g, b values
      obtained photographing the colour marker in fixed illumination conditions was
      used to adjust skin colour measurements. Then erythema index (E.I) on digitized
      images was calculated subtracting red value to green one by averaging procedure
      of different pixels. RESULTS: Erythema index. average value among the groups
      divided according to the conventional clinical score increased progressively from
      score 0-2, while it decreased from score 2 to score 3. The differences in E.I.
      mean values among the score groups (0 vs. 1, 1 vs. 2, 2 vs. 3) were statistically
      significant (P < 0.05). CONCLUSION: We developed a method for the measurement of
      skin erythema using digital camera, normalized r, g, b colour co-ordinate system
      and computerized calculation of E.I. Clinical usefulness of our method for
      absent, slight and moderate erythema, was demonstrated. For intense erythema
      lesions we did not find a correspondence between clinical and computerized
      evaluation, probably due to other factors involved in skin inflammation (e.g.
      oedema).

PMID- 12060472
TI  - Simple objective measurement of the cutaneous delayed-type hypersensitivity
      reaction to tuberculin using spectrophotometry.
AB  - BACKGROUND/AIMS: A number of subjective methods have been used to quantify the
      extent of the cutaneous delayed-type hypersensitivity (DTH) reaction. However,
      because of their subjective nature, significant differences in measurements may
      be seen between individual observers or laboratories unless thorough training is
      given to each observer. METHODS: Objective measurement of the DTH reaction using
      a hand-held spectrophotometer is described. Guinea pigs were primed using
      inoculation with Mycobacterium bovis Bacille Calmette-Guerin and challenged five
      weeks later in the shaved flank with three doses of bovine purified protein
      derivative. The extent of the ensuing DTH reaction was measured 24 and 48 h
      later. Spectrophotometric measurement of the reaction site was compared with a
      control region of skin on each animal and expressed as the change within a
      standard colour space. Data obtained with the spectrophotometer was compared with
      the subjective measurement of the area of the DTH reaction by an experienced
      operator. RESULTS: The measurements obtained with the spectrophotometer
      correlated very closely with conventional measurement of the reaction area by a
      trained operator. The reaction size in square mm and changes along the red/green
      colour axis was correlated most strongly. CONCLUSION: Spectrophotometric
      measurement of the DTH reaction had advantages over conventional measuring
      techniques in terms of speed, reproducibility and reduced operator to operator
      variation. We conclude that the cutaneous DTH reaction may be simply and
      objectively quantified with the use of a hand-held spectrophotometer.

PMID- 12060473
TI  - Skin reflectance-spectra and colour-value dependency on measuring-head aperture
      area in ordinary reflectance spectrophotometry and tristimulus colourimetry.
AB  - BACKGROUND/AIMS: Measurement of skin colour has become increasingly popular in
      the study of dermatology with the increased availability of portable instruments.
      However, different instruments have been reported as giving different results
      from measurement of the same skin region. The aim of this study was to examine
      the effects of differences in measuring-head aperture area on skin reflectance
      spectra and colour values. METHODS: We measured both reflectance spectra and CIE
      L*a*b* values of the skin in five different anatomical regions on 10 subjects
      using two MINOLTA reflectance spectrometers that were identical apart from the
      aperture area of the measuring heads (diameters: 5 and 11 mm). For comparison,
      data were also obtained from a skin-coloured tile. RESULTS: Skin reflectance
      values measured with the wider-aperture instrument were higher than those
      measured with the other, irrespective of anatomical location. The differences
      between the two were near zero at an incident light wavelength of 400 nm, but
      increased to around 10% of the reflectance value at 700 nm, increasing
      exponentially with incident light of increasing wavelength. Skin colour was
      observed to be brighter, redder and yellower, in CIE-L*a*b* expression, when
      measured with the wider-aperture instrument. The differences between measurements
      obtained from the skin-coloured tile were much smaller. CONCLUSION: Skin
      reflectance and colour values measured with reflectance instruments are not
      absolute data but depend on the aperture area of the measuring head. This is
      probably due to variations in the proportion of longer-wavelength light reflected
      from the skin and collected by the instrument.

PMID- 12060474
TI  - Development and validation of a semiautomatic image analysis system for measuring
      skin desquamation with D-Squames.
AB  - BACKGROUND: D-Squames, have gained wide acceptance for assessing skin
      desquamation. The amount of corneocytes adhering to D-Squames can be assessed
      visually by trained observers or by computerized image analysis. Different image
      analysis algorythms for the evaluation of D-Squames have been published but have
      not been compared with each other. It was our aim to develop an image analysis
      system that does not require an expensive image analysis programming tool but
      should be optimized for routine tasks of analysing large numbers of samples. A
      second objective of this study was to compare two published image analysis
      algorythms and visual grading. MATERIAL AND METHODS: The hardware components of
      the system are a CCD camera connected to a frame grabber card and a light box
      equipped with fluorescent tubes on two sides that provide a relatively cool,
      diffuse and even illumination of the sample. The following features were included
      into the software: generation and identification of bar codes for sample
      identification; semiautomatic recognition of ROI (region of interest),
      integration of study design into the analysing process, rapid calculation of
      desquamation index (DI: integration of the per cent area covered by scales and
      their thickness distribution) and/or scaling index (SI: distribution of grey
      values), data storage and export for further analysis. In a first step the system
      was validated by examining D-Squames covering a wide range of desquamation, by
      examining different ROI shapes (circle and square), by performing repeat
      measurements with different positions of the samples and by repeat measurements
      after re-callibrating the system. In a second step the effect of treatment with
      different moisturizers was evaluated by the two image analysis parameters DI and
      SI and compared with hydration measurements (Corneometer). RESULTS: The shape of
      the ROI showed no influence on the results (variability < 5%). Reproducibility of
      measurements was satisfactory (COV CDI): 1.7%, COV (SI): 2.6%). There was a good
      correlation between image analysis results and visual evaluation (means of 3
      technicians) (r = 0.986) as well as between the two different image analysis
      parameters DI and SI (r = 0.971). In the clinical study moisturizer treatment
      resulted in variable reduction of desquamation that was closely correlated with
      increase in stratum corneum hydration (r = 0.97). CONCLUSION: Analysing D-Squames
      with the image analysis system proved to be reproducible, independent of the
      shape of ROI, cost effective and fast and easy to operate. It has shown to be a
      suitable and reliable method for the objective determination of desquamation
      levels.

PMID- 12060475
TI  - Contrast enhanced phototrichogram pinpoints scalp hair changes in androgen
      sensitive areas of male androgenetic alopecia.
AB  - BACKGROUND/AIM: In male androgenetic alopecia (AGA), global changes of scalp hair
      observed on many years are the cumulative result of discrete changes. Such
      changes reflect structural and/or functional modifications occurring at the level
      of individual hair follicles. The patterning of scalp hair loss is the phenotypic
      expression of clusters of hormone sensitive follicles located in specific scalp
      areas. The aim of this study was to evaluate, in 21 untreated male subjects with
      AGA, the relation between various hair measurements using a new validated
      photographic method with clinical staging (modified Norwood-Hamilton scale) as
      compared with five controls. METHODS: As recently demonstrated by comparison with
      transverse sectioning of scalp biopsies, dynamic changes occurring at the level
      of individual hair follicles can be accurately explored with the contrast
      enhanced phototrichogram technique (CE-PTG). This is a further improvement of the
      PTG (combined analysis of two photographs taken at 48 h interval) using contrast
      enhancement together with the scalp immersion proxigraphy method. Visible hair
      counts per unit area were first evaluated on photographs without and with CE.
      Then other scalp hair variables (anagen hair counts and proportion of thin hair
      (<or= 40 microm thickness)) were established on CE-PTGs. Thickness of scalp hair
      sampled during the preparation of these sites was also calibrated against an
      objective ruler with a light microscope. RESULTS: We confirm that the CE improves
      hair detection. Controls showed higher densities in the top of the head sites as
      compared with the occipital ones. In the presumably less hormone responsive scalp
      occipital sites, AGA subjects did not differ from controls. The top of the head
      sites, i.e. highly androgen sensitive areas of AGA subjects showed a reduction of
      total and anagen hair counts as compared to controls. These changes were observed
      even in mildly affected subjects. The clinical severity of AGA seems to be
      related to the reduction of anagen counts and the associated relative increase of
      thin hair. Because the thinnest hair usually lacks pigmentation, they escape
      detection by PTG in the absence of contrast enhancement. The CE-PTG also detects
      higher proportions of thin hair at early stages of AGA as compared with light
      microscopy. This probably reflects lack of control during the sampling process,
      i.e. the clipping- collection-display sequence required for light microscopy
      observations. CONCLUSION: These results indicate that CE-PTG is a powerful tool
      for analysis of hair growth and loss and may cast some doubt on results obtained
      with other methods. The potential use of the CE-PTG method for calibration of
      innovative tools is also alluded to. Indeed encouraging results have been
      obtained with the scalp coverage scoring (SCS) method. These SCS scores were
      correlated with shortening of anagen phase and hair miniaturization, the two
      processes apparently involved in the clinical development of male AGA.

PMID- 12060476
TI  - Automation of a series of cutaneous topography measurements from silicon rubber
      replicas.
AB  - BACKGROUND/AIMS: Skin relief is a matter of interest for dermatologists and
      surgeons. One of the methods available for surface topography measurement is
      based on 3D profilometry using skin surface replicas. and most studies use
      statistical results obtained from a large number of skin replica samples. The
      advent of optical profilometers (without contact) made it possible to remove the
      solid positive replica and to reduce the duration of the profilometric data
      acquisition. Nevertheless this saving of time, to be really interesting, needs to
      automate the data acquisition on a series of negative replicas. METHODS/RESULTS:
      By adding a video camera to the optical profilometer and then by processing the
      resulting images, we have conceived a system able to carry out topographic
      measurements on a series of replicas loosely organized on a sample holder,
      without any human intervention. The silicon replicas in use have a very light
      colour: nearly white, sometimes slightly blue or green. The laser spot of the
      profilometer is so luminous that its red colour looks white through the camera.
      When choosing a replica holder with a matt dark colour and marking the left upper
      corner of the study area on the replica in black ink, the colours to be
      differentiated on the image are then close to the black one and the white one. We
      accordingly change the colour camera image into a black and white image (with 256
      grey levels) and then carry out thresholdings to separate the different objects
      or information included in this image. With the use of a perfectly circular
      replica, of an accurately known size, laid on the sample holder at the center of
      the area filmed by the camera, we adjust the threshold level, which allows
      separation of the replica from its holder. We then move this calibrated replica
      in order to find the relationship between the size in pixels and the real size on
      the sample holder, in various positions of the video image. The software has four
      main built-in stages: Moving the sample holder beneath the sensor until a part of
      a replica is detected in the field of view of the camera; Moving the sample
      holder until this replica lies just in the middle of the image given by the
      camera; Recognition of the mark of the upper left corner of the surface area to
      be measured out inside this replica; and Moving the sample holder until the laser
      spot of the profilometer coincides with the origin of the surface area to be
      measured out, then carrying out this measurement. From the upper left corner of
      the sample holder, a scanning, line-by-line or column-by-column (according to the
      selected priority direction), is carried out until the successive replicas are
      found, and is stopped as soon as the number of replicas entered by the operator
      is reached. CONCLUSION: The simplicity of the algorithms used makes it possible
      to distinguish the next measurement area from the preceding one in a few seconds.

PMID- 12060477
TI  - Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic
      resonance imaging and spectroscopy: relationships with sex and presence of
      cellulite.
AB  - BACKGROUND: Little is still known concerning subcutaneous adipose tissue and
      cellulite, and controversial questions are still under discussion. AIMS: Magnetic
      resonance imaging and spectroscopy were used to address two unresolved questions
      relating to the anatomy and physiology of subcutaneous adipose tissue. METHODS:
      Using high spatial resolution magnetic resonance imaging we characterized the
      topography of the dermo- hypodermal junction, and the three-dimensional
      architecture of the subcutaneous fibrous septae. Using proton spectroscopy, we
      measured water and lipid fractions within a fat lobule, and T1 and T2 values of
      the detected compounds. All these data were analysed according to sex and
      presence of cellulite. RESULTS: MR imaging quantified deeper indentations of
      adipose tissue into the dermis, and evidenced for the first time a great increase
      in the thickness of the inner fat layer in women with cellulite. Moreover, 3D
      reconstruction of the fibrous septae network showed a higher percentage of septae
      in a direction perpendicular to the skin surface in women with cellulite; but our
      study also depicted the tortuous aspect of this network. MR proton spectroscopy
      could not show any differences related to sex or presence of cellulite concerning
      T1 and T2 relaxation times of the detected compounds within a fat lobule, neither
      the unsaturated lipid fraction, the saturated lipid fraction, nor the water
      fraction. CONCLUSIONS: Magnetic resonance imaging showed that the 3D architecture
      of fibrous septae couldn't be modelled simply as perpendicular planes for women
      and tilted planes at 45 degrees for men. MR spectroscopy did not confirm the
      hypothesis of increased water content in the adipose tissue of women with
      cellulite as suggested by others, except if such water would be located in the
      connective septae.

PMID- 12060478
TI  - Age-dependent response of energy metabolism of human skin to UVA exposure: an in
      vivo study by 31P nuclear magnetic resonance spectroscopy.
AB  - PURPOSE: The aim of our study was to evaluate the in vivo energy metabolism of
      human skin as a function of age, in conditions of rest and after a mild stress
      caused by a suberythemal UVA irradiation. METHODS: The kinetics of UVA-induced
      modifications in high-energy phosphorylated metabolites of young and old skins
      were non-invasively monitored over a period of 24 h using 31P nuclear magnetic
      resonance spectroscopy. In vivo 31P spectra were obtained on the ventral aspect
      of the wrist, using a NMR Imaging Spectrometer equipped with a double-tuned
      surface coil. Concentrations of phosphocreatine, inorganic phospate, adenosine
      tri-phosphate, phosphomono and phosphodiesters were calculated from the spectra
      and results were expressed as relative concentrations. A total of 20 subjects
      were enrolled in this study (n = 10 for the age group below 25 years and n = 10
      for the age group above 55 years). A second experiment was then performed on 10
      old subjects (mean age 60) who were treated on one wrist, twice a day for one
      month prior to UVA irradiation, with a product that contained active ingredients
      to restore barrier function and modulate the inflammatory response, the other
      wrist being an untreated control. RESULTS: Baseline levels of phosphorylated
      metabolites were similar in young and old skins. A suberythemal dose of UVA (6
      J.cm-2) led to a significant decrease in the PCr/Pi ratio (index of energy
      status) and a significant increase in the PME/PDE ratio (index of cellular
      turnover rate of lipid-related metabolites) within 1 h. The observed variations
      were transient and the recovery was complete at T + 24 h post-UVA, although
      recovery was significantly slower in the older group. The disturbances were
      significantly reduced after treatment of the older skin with a formula that
      restored barrier function of the stratum corneum and modulated the inflammatory
      response. CONCLUSION: (i) baseline levels of energy metabolites in skin do not
      seem to vary with age; (ii) low dose UVA irradiation induces a rapid response in
      the energy metabolism of the skin; (iii) the kinetics of the response and
      recovery after an aggression by UVA suggest that older skin has significantly
      less energy rebound after a stress situation than younger skin; (iv) the energy
      reserve in older skin can be protected efficiently against UVA-induced stress by
      restoring barrier function and modulating the inflammatory response.

PMID- 12060479
TI  - Instrumental evaluation of retinoid-induced skin irritation.
AB  - BACKGROUND/PURPOSE: Retinoids like tazarotene are approved for the treatment of
      chronic plaque psoriasis. In the beginning of topical retinoid therapy, 15-20% of
      the patients suffer from mild to moderate adverse reactions with burning and
      erythema. The aim of the study was to find predicative parameters of the
      individual irritative potential and to suggest options to reduce these initial
      irritations. METHODS: Twenty in-patients with different skin types (1 + 2: 11, 3
      + 4: 9), with chronic plaque psoriasis were included in this open study. In each
      patient, 7 randomized plaques on the forearm were treated for 14 days on
      different ways: test area 1: morning (m) and evening (e) placebo, test area 2:
      placebo (m) and tazarotene 0.05% (e), test area 3: placebo (m) and tazarotene
      0.1% (e), test area 4: calcipotriol (m) and calcipotriol (e), test area 5:
      mometasone furoate (m) and tazarotene 0.05% (e), test area 6: mometasone furoate
      (m) and tazarotene 0,1% (e), test area 7: placebo (m) and tazarotene in
      increasing concentrations (e), test area 8: healthy skin for control. Before and
      after therapy, skin barrier function, blood flow and plaque thickness in 20-MHz
      sonography were assessed in different test areas intraindividually by non-
      invasive biophysical measurements. RESULTS: After 14 days of therapy, tazarotene
      0.05% and 0.1% produced a stronger increase of laser Doppler flow in patients
      with skin type 1 and 2 than in patients with skin type 3 and 4. When using the
      combination therapy of tazarotene and mometasone, the laser Doppler flow was
      significantly lower than in tazarotene as monotherapy. 20-MHz-ultrasound showed a
      significant decrease in the thickness of the echo-poor band in all topical
      therapy regimens compared to placebo. Patients of skin type 1 and 2 reached a
      higher density of the dermis than patients of skin type 3 and 4, meaning a
      stronger decrease of inflammatory infiltration and acanthosis. CONCLUSION:
      Adapting retinoid therapy to the patient's skin type can reduce the initial
      irritative side-effects. During the first days, patients with skin type 1 or 2
      should add a medium potency corticosteroid. Stronger skin irritation caused by
      tazarotene therapy increases therapy effects.

PMID- 12060481
TI  - Genetic profile of acute myeloid leukemia.
AB  - Understanding genomic events and the cascade of their effects in cell function is
      crucial for identifying distinct subsets of acute myeloid leukemia and developing
      new therapeutic strategies. Conventional cytogenetics, fluorescence in situ
      hybridization investigations and molecular studies have provided much information
      over the past few years. This review will focus on major genomic mechanisms in
      acute myeloid luekemia and on the genes implicated in the pathogenesis of
      specific subtypes.

PMID- 12060482
TI  - Acute myeloid leukemia: treatment of adults under 60 years.
AB  - Current chemotherapy with advanced supportive care will enable 75-80% of acute
      myeloid leukemia patients aged 60 years or under to enter complete remission.
      Several regimens achieve broadly similar results. For patients who enter complete
      remission, the overall relapse risk is now 45-50%, but this is highly variable
      and is primarily determined by the biology of the disease. Cytogenetics are
      strongly influential in response to induction and consolidation with t(15:17),
      t(8:21) and inv(16) either occurring alone or with additional abnormalities
      having a relapse risk of about 30% and complex changes, abnormal 3q or
      abnormalities of chromosomes 5 and 7 resulting in a lower remission rate and a
      rapid relapse cumulating to 80%. FLT3 mutations occur in 25% of patients and are
      an independent predictor of relapse and, when combined with cytogenetics,
      adversely influence the prognosis in each cytogenetic risk group. Recent
      prospective collaborative group trials have endeavored to evaluate allogeneic and
      autologous bone marrow transplant against or in addition to consolidation
      chemotherapy. Suboptimal treatment delivery emerged as a problem. When the
      results were reported on an intention-to-treat basis, no overall survival
      advantage was consistently seen for either type of transplant. However, a
      significant reduction in risk of relapse was usually seen overall and within risk
      groups. Analysis within risk groups suggests that transplant is not indicated in
      good risk disease and continues to require evaluation in standard or poor risk
      patients. It is probable that traditional dose intensification has now reached
      its limits of tolerability, so new approaches will be required for further
      progress to be made. Modulation of chemoresistance mechanisms or immunologically
      directed chemotherapy represent immediate prospects for clinical study.

PMID- 12060483
TI  - Acute myeloid leukemia: treatment over 60.
AB  - Undertreatment of older patients with acute myeloid leukemia (AML) can explain,
      in part, their inferior outcome when compared to that of younger patients. In
      agreement with the benefit seen by patients under age 60 from high-dose cytosine
      arabinoside (Ara-C), there are dose effects in the over 60s, in particular for
      daunorubicin, in induction treatment and for the duration of postremission
      treatment. The use of these effects can partly overcome the mostly unfavorable
      disease biology in older age AML, as expressed by the absence of favorable and
      the over-representation of adverse chromosomal abnormalities as well as the
      expression of drug resistance. We recommend an adequate dosage of 60 mg/m2
      daunorubicin on 3 days in combination with standard dose Ara-C and 6-thioguanine
      given for induction and consolidation, and followed by a prolonged monthly
      maintenance chemotherapy for at least 1 year's duration. Further improvements in
      supportive care may help to deliver additional antileukemic cytotoxicity. As a
      novel approach, nonmyeloablative preparative regimens may open up the possibility
      of allogeneic transplantation for older patients with AML. Other new options like
      multidrug resistance modulators, antibody targeted therapies and molecular
      targeting are under clinical investigation. A questionnaire study in patients
      with AML showed that, according to patients' self-assessment, intensive and
      prolonged treatment did not result in a diminished quality of life. This finding
      did not vary by age, under or over 60 years. As the median age in this disease is
      more than 60 years, the adequate management of AML in older patients remains the
      major challenge.

PMID- 12060484
TI  - Advances in the understanding and management of acute promyelocytic leukemia.
AB  - Considerable progress has been made over the past decade in the understanding and
      management of acute promyelocytic leukemia (APL). At the laboratory level,
      molecular mechanisms underlying the arrest of differentiation that typically
      features in this malignancy, have been clarified and currently provide important
      models for addressing future investigation aimed at releasing the maturation
      block in other malignancies. In the clinic, advances in the management of APL
      have converted this rapidly fatal disease into the most frequently curable
      leukemia in adults. Use of retinoids in combinatorial protocols with
      anthracycline-based chemotherapy for front line treatment currently results in
      long-term survival and potential cure in at least 60% of newly diagnosed
      patients. Even after relapse, the disease is still curable in a high percentage
      of cases by various approaches including combinations of chemotherapy, retinoids,
      arsenic trioxide, stem cell transplantation and antibody-targeted chemotherapy.
      Genetic testing for identification of the disease-specific gene rearrangement and
      monitoring of residual disease have proved critical in establishing correct
      diagnosis and better evaluate the response to therapy at the molecular level.
      Current 'hot' issues for clinical investigation include: (i) better understanding
      and management of the severe coagulopathy present at diagnosis in most patients;
      (ii) the definition of risk categories to improve identification of patients at
      highest risk of relapse and (iii) the translation of successful differentiation
      therapy to other leukemia subsets.

PMID- 12060485
TI  - Stem cell transplantation for leukemias following myelodysplastic syndromes or
      secondary to cytotoxic therapy.
AB  - Two main forms of therapy-related myelodysplastic syndrome and acute myeloid
      leukemia (t-MDS/AML) have been recognized. The most frequent type, occurring
      after treatment with alkylating agents, is characterized by abnormalities of
      chromosomes 5 and/or 7 and t-MDS/AML following treatment with topoisomerase II
      inhibitors and is associated with molecular aberrations of MLL (11q23) and AML-1
      (21q22). Individuals with certain polymorphisms associated with impaired
      detoxification of cytotoxic agents have an increased risk of developing MDS or
      AML after treatment of unrelated cancers. Multidrug chemotherapy is less
      effective for patients with MDS, or AML following MDS, or t-MDS/AML when compared
      with primary AML, and results in lower complete remission (CR) rates and lower
      long-term survival. Patients with good risk cytogenetic features, such as t(15;
      17), t(8; 21) and inversion 16 are an exception as their treatment outcome is
      comparable with primary AML patients. Patients who attain a polyclonal and/or a
      cytogenetic CR may be candidates for autologous stem cell transplantation. For
      the remaining patients, the only curative option is allogeneic stem cell
      transplantation with stem cells from a histocompatible sibling or an alternative
      donor. Reduced intensity conditioning regimens may be considered for patients
      older than 50 years or patients with comorbidities. The advice is to treat
      patients early after diagnosis and preferably before progression as these
      patients have the highest chance of a favorable outcome.

PMID- 12060487
TI  - A bovine papillomavirus-1 based vector restores the function of the low-density
      lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line: Correction.

PMID- 12060488
TI  - The cloning, genomic organization and tissue expression profile of the human DLG5
      gene: Correction.

PMID- 12060489
TI  - Cytokines as therapeutic drugs.
AB  - Cytokines are a growing group of proteins that are responsible for the
      communication of cells of the immune system, hematopoietic cells, and other cell
      types. They play a dominant role in various diseases, particularly in promoting
      and perpetuating inflammation. Cytokine production is a reaction of the body to a
      pathologic state to restore homeostasis. In such cases, the therapeutic
      intervention should support the reaction of the body by giving the cytokine
      itself (agonistic therapeutics). In other cases, manifestation of a disease
      results from an overproduction of cytokines, making cytokine antagonists
      desirable therapeutic drugs. Furthermore, cytokines may be good candidates as
      cancer therapeutics, especially to support the restoration of blood cell
      populations after chemotherapy or radiation.

PMID- 12060490
TI  - Monocyte chemoattractant protein-1-induced activation of p42/44 MAPK and c-Jun in
      murine peritoneal macrophages: a potential pathway for macrophage activation.
AB  - The role of monocyte chemoattractant protein-1 (MCP-1) in mediating the
      infiltration and activation of monocytes/macrophages into the sites of
      inflammation or tumor growth is well documented, but the molecular mechanism(s)
      involved in the process is poorly understood. In the current investigation, we
      demonstrate activation of the p42/44 MAPK-mediated signal transduction in murine
      peritoneal macrophages on stimulation with MCP-1 (10-100 ng/ml) in vitro. The
      p42/44 MAPK activation was determined by studying the expression of the
      phosphorylated p42/44 MAPK (Thr202/Tyr204) in the MCP-1-treated macrophages. This
      response was found to be rapid and time dependent, detectable within 5 min of MCP
      1 stimulation. PD98058 (5-50 microM), a specific inhibitor of MAPK kinase (MEK)
      inhibited the p42/44 MAPK phosphorylation, indicating the specificity of the
      response. Furthermore, the MCP-1-induced phosphorylation of p42/44 MAPK was found
      to be blocked by pertussis toxin (100 ng/ml), tyrosine kinase inhibitor-genestein
      (10 ng/ml), PI3K inhibitor-wortmannin (20-200 microM), and anti-CCR2 antibody
      (2.5 microg/ml). Additionally, phosphorylation of JNK and activation of the
      transcription factor, c-Jun, were also noted in response to MCP-1 treatment.
      Lastly, the MCP1-induced p42/44 MAPK activity was correlated with the functional
      activation of macrophages by demonstrating the dose-specific inhibition of actin
      polymerization, macrophage-mediated tumor cell cytotoxicity, and tumor necrosis
      factor-alpha (TNF-alpha) transcription/production afforded by PD98059 in the MCP
      1-treated macrophages. Taken together, these data suggest the involvement of the
      p42/44 MAPK/c-Jun pathway in the signal transduction process, leading to
      activation of murine peritoneal macrophages.

PMID- 12060491
TI  - In vitro activation of murine peritoneal macrophages by monocyte chemoattractant
      protein-1: upregulation of CD11b, production of proinflammatory cytokines, and
      the signal transduction pathway.
AB  - The CC chemokine monocyte chemotactic protein-1 (MCP-1) is a major mediator of
      monocyte/macrophage infiltration at the inflammatory sides under both physiologic
      and pathologic conditions. We report the ability of MCP-1 to activate murine
      peritoneal macrophages in vitro for enhanced expression of CD11b, macrophage
      mediated cytotoxicity, and production of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1 (IL-1). The macrophages treated with MCP-1 in vitro displayed
      significant cytolytic activity toward TNF-alpha-sensitive L929 cells in a dose
      dependent manner. The macrophage-mediated L929 cytotoxicity was blocked in the
      presence of anti-TNF-alpha antibodies, suggesting the involvement of TNF-alpha.
      Production of TNF-alpha and IL-1 macrophages on MCP-1 treatment was maximum at 24
      h of incubation with 100 ng/ml MCP-1. Enhanced TNF-alpha and IL-1beta mRNA
      expression was also demonstrated by RT-PCR, which revealed transcription of
      interferon gamma (IFN-gamma), IL-12, and related T cell-specific chemokine genes,
      KC and IP-10, in the MCP-1-treated macrophages. The pharmacologic inhibitors
      pertussis toxin (100 ng/ml), wortmannin (200 ng/ml), H-7 (10 microM), PD98059 (25
      microM), and genistein (10 microg/ml) significantly inhibited TNF-alpha and IL-1
      production in the MCP1-treated macrophages, suggesting the involvement of G
      proteins, phosphoinositol-3-kinase (PI3K), protein kinase C, p42/44 MAPK, and
      tyrosine kinases in this process.

PMID- 12060492
TI  - The proximal promoter region is essential for lipopolysaccharide induction and
      cyclic AMP inhibition of mouse tumor necrosis factor-alpha.
AB  - Bacterial lipopolysaccharide (LPS) induces a rapid and transient increase in
      transcription of the tumor necrosis factor-alpha (TNF-alpha) gene in cells of
      monocyte/macrophage lineage. This study examines the role of potential regulatory
      elements within the proximal promoter region of the mouse TNF-alpha gene in LPS
      induction and cyclic AMP (cAMP)-mediated inhibition of TNF-alpha in RAW 264.7
      murine macrophage-like cells. Transfection of proximal promoter chloramphenicol
      acetyltransferase (CAT) reporter constructs demonstrated that this region is LPS
      inducible in murine RAW 264.7 cells, with a 5.9-fold increase over nonstimulated
      transfectants. Site-specific mutations of the ETS, activated protein-1 (AP
      1)/cAMP-responsive element (CRE)-like, or NF-kappaB-like motifs within this
      region caused a reduction in the LPS response by 52%, 46%, and 51%, respectively.
      LPS induction of the proximal promoter-CAT reporter construct was reduced by >40%
      by the addition of 8-bromo-cAMP (8-Br-cAMP). To determine the role of the
      proximal promoter region in the context of the entire TNF-alpha gene, we produced
      a hemagglutinin (HA)-tagged genomic TNF-alpha construct that contains a deletion
      of the proximal promoter region. Transfection of this construct into RAW 264.7
      cells demonstrated a decrease in LPS-induced transcripts as well as a lack of
      response to cAMP. This suggested an essential role for this regulatory region in
      LPS-induced activation and cAMP inhibition of mouse TNF-alpha gene transcription
      in murine macrophages.

PMID- 12060493
TI  - Induction of IL-1Ra in resistant and responsive hepatitis C patients following
      treatment with IFN-con1.
AB  - Hepatitis C virus (HCV) infection is resistant to interferon-alpha (IFN-alpha) in
      some patients. The mechanism of this resistance is unknown. Interleukin-1
      receptor antagonist (IL-1Ra) is induced by IFN-alpha and is a good indicator of
      IFN activity. In the current study, we compared IL-1Ra levels in rapid virologic
      responders and flat responders who showed resistance to IFN. Three groups of
      patients were examined, including those who received a single dose of consensus
      IFN (IFN-con1), patients who received daily IFN-con1 for 1 week, and patients who
      received IFN-con1 daily for 24 weeks. Serum IL-1Ra, IL-6, and HCV RNA were
      measured serially in all groups. Serum IL-1Ra levels increased rapidly in all
      patients with hepatitis C after IFN-alpha administration, irrespective of their
      virologic response. IL-1Ra levels remained elevated at 1 week but were similar to
      baseline by week 2 of treatment in patients receiving continuous therapy. IL-6
      levels also increased acutely but rose more slowly than IL-1Ra levels. The
      increase in IL-1Ra and IL-6 observed in both flat and rapid virologic responders
      indicates that IFN receptors are functioning in patients with IFN-resistant
      hepatitis C and that the lack of response is related to other virologic or
      immunologic factors.

PMID- 12060494
TI  - Association of the chaperone glucose-regulated protein 58 (GRP58/ER-60/ERp57)
      with Stat3 in cytosol and plasma membrane complexes.
AB  - Glucose-regulated protein 58 (GRP58/ER-60/ERp57), best known as a chaperone in
      the endoplasmic reticulum lumen, was previously identified by us as one of
      several accessory proteins in the S100 cytosol fraction of human hepatoma Hep3B
      cells that was differentially coshifted by anti-Stat3 antibody in an antibody
      subtracted differential protein display assay. In the present study, the
      association between GRP58 and Stat3 in different cytoplasmic compartments was
      evaluated using cross-immunoprecipitation and cell-fractionation techniques. In
      the S100 cytosol fraction, three different anti-GRP58 polyclonal antibodies (pAb)
      cross-immunoprecipitated Stat3 (but not Stat1), and, conversely, anti-Stat3 pAb
      cross-immunoprecipitated GRP58. Both cytosolic Stat3 and GRP58 eluted during
      Superose-6 gel-filtration chromatography in complexes of size 200-400 kDa
      (statosome I), and anti-Stat3 pAb cross-immunoprecipitated GRp58 from these FPLC
      elution fractions. Using differential sedimentation and density equilibrium
      flotation methods, Stat3 and GRP58 were observed to be coassociated with
      cytoplasmic membranes enriched for the plasma membrane marker 5' nucleotidase but
      not with those containing the endoplasmic reticulum marker BiP/GRP78. The Stat3
      and GRP58-containing plasma membrane fraction also contained Stat1, Stat5b, and
      gp130. Stat activation by orthovanadate caused the accumulation of PY-Stat3 in
      the GRP58-containing plasma membrane fraction. However, this PY-Stat3 was DNA
      binding deficient. Likewise, excess exogenous recombinant human GRP58 prepared
      using a baculovirus expression system preferentially inhibited Stat3 DNA-binding
      activity in the S100 cytosol, suggesting that GRP58 may sequester activated
      Stat3. The new data confirm the association between GRP58 and Stat3 in cytosolic
      200-400-kDa statosome I complexes and show that both GRP58 and Stat family
      members coassociate in the plasma membrane compartment. We suggest that the
      chaperone GRP58 may regulate signaling by sequestering inactive and activated
      Stat3.

PMID- 12060495
TI  - Cytokine responses in young and old rhesus monkeys: effect of caloric
      restriction.
AB  - Caloric restriction (CR) is the only known intervention demonstrated to retard a
      great variety of aging processes, extend median and maximum life-span, and
      decrease the incidence of age-associated diseases in mammals. Paralleling
      findings from rodent studies, studies in rhesus monkeys (Macaca mulatta) suggest
      that CR may retard many age-sensitive parameters in primates. A recent study in
      rhesus monkeys showed age-related dysregulation of cytokine levels. Specifically,
      age-related increases in interleukin-10 (IL-10) and IL-6 proteins were observed
      in supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood
      mononuclear cells (PBMCs), and interferon-gamma (IFN-gamma) protein exhibited an
      age-related decrease in phytohemagglutinin (PHA)-stimulated PBMCs. To investigate
      effects of CR on age-related changes in cytokine production, we obtained PBMCs
      from control and CR rhesus monkeys aged 6-7 and 22-25 years. We evaluated IL-10
      and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein
      and gene expression after PHA stimulation. The results revealed significantly
      higher levels of IFN-gamma protein and gene expression in aged monkeys on CR for
      2 years compared with controls. No significant CR effects were observed on IL-10
      and IL-6 protein levels. IFN-gamma plays an important role in the initial defense
      mechanism against viral and microbial disease and cancer. Altered regulation of
      IFN-gamma in old CR rhesus monkeys may be a key factor in reducing cancer
      incidence and other age-associated diseases.

PMID- 12060496
TI  - Adenoviral-mediated gene transfer of lymphotactin to the lungs of mice and rats
      results in infiltration and direct accumulation of CD4+, CD8+, and NK cells.
AB  - Chemokines are small 8-12-kDa chemotactic cytokines that were initially
      characterized for their ability to control leukocyte trafficking and, to a lesser
      extent, leukocyte function. Lymphotactin was first described as a T lymphocyte
      specific chemotactic factor. However, it has since been shown to also be a potent
      attractant for natural killer (NK) cells. The chemotactic properties of
      lymphotactin suggested from in vitro data prompted us to study the in vivo
      activity of this chemokine. We constructed an adenovirus vector expressing murine
      lymphotactin (Ad mLym) and used this construct to overexpress lymphotactin in the
      lungs of both mice and rats, with similar outcomes. In brief, the accumulation of
      CD4(+) and CD8(+) T cells and NK cells surprisingly demonstrated slow kinetics,
      uncharacteristic of the chemoattractant potential seen with other chemokines.
      Lymphocyte accumulation in the lung was not evident prior to 24 h after gene
      transfer and reached a peak by day 7 in mice and day 14 in rats. Interestingly,
      the cellular infiltrate recruited to the lung by lymphotactin was a heterogeneous
      mixture of lymphocytes, monocytes, and neutrophils. Administration of Ad mLym to
      BALB/c SCID mice demonstrated that the presence of monocytes and neutrophils in
      the bronchoalveolar lavage (BAL) of wild-type BALB/c mice was likely due to the
      action of lymphotactin on lymphocytes. These findings extend the previous in
      vitro findings on the activity of lymphotactin and provide a model for studying
      the local effects of overexpressing chemokines in various tissues in vivo.

PMID- 12060497
TI  - Axillary lymph node cellular immune response to HER-2/neu peptides in patients
      with carcinoma of the breast.
AB  - HER-2/neu peptides have recently been shown to induce a proliferative response by
      peripheral CD4(+) T cells in breast cancer patients. To investigate potential
      differences in the local cellular immune response between breast cancer patients
      with and without nodal metastases, lymphocytes were isolated from axillary lymph
      nodes from patients with breast cancer, and proliferative and cytokine responses
      to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph
      nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20
      x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu
      peptides at 50 microg/ml and with control antigens. Incorporation of tritium
      labeled thymidine was determined 4 days later. The levels of the cytokines
      interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at
      priming and at restimulation with HER-2/neu peptides using a cytokine-specific,
      double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated
      from the axillary lymph nodes of the patients mounted significant cellular immune
      response to HER-2/neu peptides, manifested by proliferation and specific cytokine
      elaboration. Proliferative responses to HER-2/neu peptides were seen in
      lymphocytes of patients with and without overexpression of HER-2/neu in the
      primary tumor. In some patients, the proliferative response to HER-2/neu peptides
      in lymphocytes from lymph nodes with metastases was absent or blunted compared
      with the response in lymphocytes from lymph nodes without metastases from the
      same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type
      1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast
      cancer patients. A Th1-specific cytokine production pattern was maintained at
      priming and restimulation with HER-2/neu peptides and was amplified with IL-12
      costimulation. These results indicate that HER-2/neu peptides can activate T
      cells in draining lymph nodes from women with invasive breast cancer. This
      activation is associated with a predominantly Th1 cytokine response, which
      suggests that conditioning with HER-2/neu peptides may be of value in the
      development of breast cancer vaccines.

PMID- 12060498
TI  - The combination of soluble IL-18Ralpha and IL-18Rbeta chains inhibits IL-18
      induced IFN-gamma.
AB  - Although the beta chain of interleukin-18 receptor (IL-18Rbeta) is required for
      signaling, the soluble (extracellular) form does not bind IL-18, and its role in
      inhibiting IL-18 is unclear. In the present study, both the soluble human IL-18
      ligand binding alpha chain (sIL-18Ralpha) and the sIL-18Rbeta chain were
      investigated for inhibition of IL-18-induced interferon-gamma (IFN-gamma)
      production in human peripheral blood mononuclear cells (PBMC), whole blood, and
      KG-1 macrophage and natural killer (NK) cell lines. Neutralization of IL-18 by
      soluble receptors was compared with that of the IL-18 binding protein (IL-18BP).
      An equimolar concentration IL-18BP inhibited 90% of IL-18 activity, whereas a 4
      fold molar excess of sIL-18Ralpha had no effect. A dimeric construct of sIL
      18Ralpha linked to the Fc domain of IgG1 (sIL-18Ralpha:Fc) increased IL-18
      activity 2.5-fold. In PBMC stimulated with lypopolysaccharide (LPS) or in whole
      blood stimulated with Staphylococcus epidermidis, 3 nM IL-18BP reduced IFN-gamma
      by 80%, whereas IL-18Ralpha:Fc had no effect. A construct of the sIL-18Rbeta
      linked to Fc (sIL-18Rbeta:Fc) did not affect IL-18-induced IFN-gamma even at 80
      fold molar excess of IL-18. However, the combination of both soluble receptors
      reduced IFN-gamma by 80%. In KG-1 cells, a 50% reduction in IL-18 activity was
      observed using an 80-fold molar excess of sIL-18Ralpha:Fc but only in the
      presence of sIL-18Rbeta:Fc. Similarly, a 50% reduction was observed using sIL
      18Rbeta:Fc in the presence of a molar excess of sIL-18Ralpha:Fc. Similar
      inhibition was observed in NK cells. These studies reveal that the combination of
      the ligand-binding and the nonligand-binding extracellular domains of IL-18R is
      needed to inhibit IL-18, whereas IL-18BP neutralizes at equimolar concentration.

PMID- 12060499
TI  - Resistance to interferons in melanoma cells does not correlate with the
      expression or activation of signal transducer and activator of transcription 1
      (Stat1).
AB  - Defects in expression or activation signal transducer and activator of
      transcription-1 (Stat1) in response to interferon-alpha2 (IFN-alpha2) have been
      implicated as a mechanism for IFN resistance in melanoma cells. To further
      determine the significance of this observation, 17 melanoma cell lines sensitive
      or resistant to the antiproliferative effects of IFN-alpha2 and IFN-beta, as well
      as 30 melanoma patient samples, were analyzed for Stat1 levels by either Western
      blot analysis or immunohistochemistry. Although the expression level varied
      between samples, all the cell lines except one and all melanoma biopsy specimens
      expressed Stat1. IFN-stimulated levels of Stat1 and Stat2, which constitute the
      transcriptional activation complexes, such as, gamma activated factor (GAF) and
      IFN-stimulated gene factor 3 (ISGF3), for IFN-stimulated gene (ISG) induction
      were assessed in melanoma cell lines. Both IFN-alpha2 and INF-beta induced
      equivalent amounts of Stat1 and Stat2 proteins in cell lines, although compared
      with IFN-alpha2, IFN-beta had greater antiproliferative effects. No significant
      differences were observed in tyrosine or serine phosphorylation of Stat1 or the
      formation of GAF or ISGF3 complexes following IFN-alpha2 or IFN-beta treatment of
      IFN-resistant or IFN-sensitive cell lines. Comparable induction of two ISGs,
      ISG54 and IFN regulatory factor-1 (IRF-1), was observed in both sensitive WM9 and
      resistant A375 cells. Therefore, we report that defects in expression or
      activation of Stat1 or Stat2 were infrequent in melanoma cell lines and tumor
      samples and did not correlate with IFN resistance. Cellular resistance to IFNs
      likely results from defective quantitative or qualitative expression of specific
      ISGs.

PMID- 12060501
TI  - An interesting response to diphencyprone (DPC) sensitization on facial warts:
      review of DPC treatment for viral warts.
AB  - BACKGROUND: This paper highlights the sometimes impressive effect of
      diphencyprone (DPC) sensitization on warts resistant to other treatments and is
      interesting in view of the fact that all the warts apparently responded, despite
      only a very small area being treated. METHODS: A 31-year-old woman with a 5-year
      history of widespread facial plane warts that had proved resistant to repeated
      treatments with cryotherapy and topical preparations was sensitized to
      diphencyprone. RESULTS: After application of DPC to the warts within only a 1
      cm(2) area of the face, all the facial warts became inflamed and resolved,
      including those not actively treated. Complete clearance occurred with no
      recurrence. CONCLUSION: DPC appears to be a valuable, safe and well-tolerated
      treatment for resistant viral warts and can be considered as a first line
      treatment. We review its use and action in this paper

PMID- 12060502
TI  - A randomised, single-blind, single-centre clinical trial to evaluate comparative
      clinical efficacy of shampoos containing ciclopirox olamine (1.5%) and salicylic
      acid (3%), or ketoconazole (2%, Nizoral) for the treatment of
      dandruff/seborrhoeic dermatitis.
AB  - BACKGROUND: The association between seborrhoeic dermatitis and dandruff and the
      yeast Malassezia furfur is well recognized. Symptoms include scalp itchiness and
      scaling. Due to its antimycotic activity, ciclopirox olamine is established as an
      effective treatment for these scalp conditions. Salicylic acid has keratolytic
      properties and aids in the removal of scales. OBJECTIVE: To compare the
      therapeutic efficacy of a shampoo containing 1.5% ciclopirox olamine and 3%
      salicylic acid (CPO/SA) with Nizoral (2.0% ketoconazole shampoo) in a study
      involving 154 subjects with dandruff - 70 of whom also had seborrhoeic dermatitis
      of the scalp. Nizoral is currently a registered treatment for dandruff and
      seborrhoeic dermatitis. METHODS: The shampoos were used three times week for 4
      weeks, with 2-week washout and follow-up periods. Clinical and self-assessments
      were made throughout treatment and after follow-up (day 43). Within and between
      treatment assessments of signs and symptoms were analysed. RESULTS: In the two
      groups, seborrhoeic dermatitis and dandruff improved significantly throughout
      treatment, with lower clinical and self-assessment scores at both the end of
      treatment (day 29) and follow-up (day 43). Only the subjects treated with CPO/SA
      shampoo showed a significant reduction in the itching of seborrhoeic dermatitis
      at these times. CONCLUSION: The study demonstrated that both CPO/SA and Nizoral
      were safe and effective in the treatment of dandruff and seborrhoeic dermatitis.

PMID- 12060503
TI  - An effective, cosmetically acceptable, novel hydro-gel emollient for the
      management of dry skin conditions.
AB  - BACKGROUND: A novel hydro-gel emollient (Doublebase) has been developed with
      improved moisturizing effects. OBJECTIVE: To test this novel hydro-gel for its
      moisturizing effect, for its potential to cause skin irritancy/allergy and for
      its clinical effectiveness and acceptability in dry skin conditions.
      METHODS/RESULTS: Skin hydration (corneometry) and trans-epidermal water loss
      (TEWL) studies with a single application in 18 volunteers confirmed its efficacy
      (p < 0.0001) and showed that it was superior to Ultrabase and Diprobase (p <
      0.001). Skin hydration studies with multiple applications in 12 volunteers also
      showed that it was superior to Ultrabase and Diprobase (p < 0.0001). Irritation
      tests in 74 eczema-prone patients resulted in only one mild reaction, and allergy
      tests in 99 healthy volunteers elicited no positive reactions. The clinical
      acceptability and effectiveness of Doublebase was demonstrated in an open study
      of 78 patients with dry skin conditions. CONCLUSION: Doublebase may be considered
      a suitable preparation that can be used effectively by most patients with dry
      skin conditions.

PMID- 12060504
TI  - Topical application of penciclovir cream for the treatment of herpes simplex
      facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled
      trial.
AB  - BACKGROUND: Herpes simplex facialis/labialis (HSFL) is a common infectious skin
      disorder, caused mainly by herpes simplex virus (HSV) type 1, for which the
      topical application of a cream containing an antiviral agent for treatment of the
      disease has been widely utilized. OBJECTIVE: To explore the efficacy of the
      topical application of 1% penciclovir cream in the treatment of HSFL, and to
      compare its efficacy and safety with 3% aciclovir cream. METHODS: A total of 248
      patients with a diagnosis of HSFL were randomly allocated to one of the two
      treatment groups (n = 124 each), using stratified randomization based on a table
      of random numbers. Before treatment (day 0) and at every visit (days 3, 5 and 7)
      during the study, the sign and symptom scores were recorded by the same doctor.
      RESULTS: Excluding 23 patients (10 in the penciclovir and 13 in the aciclovir
      groups), 225 completed the study, and no severe adverse events were noted with
      any of the treatment regimens. Results show that an encouraging improvement in
      the clinical course was found simultaneously for patients with each episode type
      and each treatment assignment. There were no significant differences in terms of
      efficacy endpoint, clinical cure rate, and safety between the two treatment arms,
      but there was a trend towards a shorter time to resolution of all symptoms,
      cessation of new blisters, and loss of crust (p <or= 0.08) in penciclovir-treated
      primary patients. In addition, the clinical scores in penciclovir-treated primary
      patients were significantly lower than those in the respective aciclovir-treated
      patients on treatment day 5 (p < 0.01) and day 7 (p < 0.05). CONCLUSION: Topical
      1% penciclovir cream is as convenient and as effective as 3% aciclovir cream for
      the treatment of HSFL. Penciclovir cream may provide a good topical alternative
      to other types of therapy in the future.

PMID- 12060505
TI  - Fluconazole versus ketoconazole in the treatment of tinea versicolor.
AB  - BACKGROUND: A number of effective topical therapies are available for the
      treatment of tinea versicolor (TV). However, topical antifungals are difficult to
      apply to a large body surface area and for this reason TV is perhaps more easily
      treated with systemic agents. METHODS: A total of 128 patients with TV, aged 15
      55 years, were entered into a randomized, double-blind, clinical trial comparing
      the efficacy and tolerance of two regimens of oral treatment for TV. The patients
      were randomly divided in two groups: group 1 received two 150 mg capsules of
      fluconazole in a single dose repeated weekly for 2 weeks; and group 2 received
      two 200 mg tablets of ketoconazole in a single dose repeated weekly for 2 weeks.
      Diagnosis of TV was made clinically by direct KOH preparation and Wood's lamp
      examination. RESULTS: Of 128 patients, 100 completed the study and no major side
      effects were noted between the two treatment regimens. Results of the study
      showed no significant differences in efficacy, safety and tolerability between
      the two treatment regimens. The maximal cure rate was achieved at 8 weeks from
      the start of treatment and decreased slightly afterwards. CONCLUSIONS:
      Fluconazole and ketoconazole demonstrated similar efficacy in the treatment of
      TV. We also demonstrated a lack of correlation between mycological cure and
      hypopigmentation at the end of treatment (2 weeks) and the usefulness of Wood's
      lamp examination in detecting cure of TV.

PMID- 12060506
TI  - Comparison of a single 400 mg dose versus a 7-day 200 mg daily dose of
      itraconazole in the treatment of tinea versicolor.
AB  - BACKGROUND: Tinea (pityriasis) versicolor is a superficial infection of the
      stratum corneum by the lipophilic fungus known as Malassezia furfur. OBJECTIVE:
      To evaluate the efficacy and safety of a 400 mg single dose or 7-day 200 mg daily
      dose of itraconazole capsules in the treatment of mycologically confirmed
      pityriasis versicolor. METHODS: A total of 50 patients were entered into a
      randomized, open, clinical trial comparing a 400 mg single dose (n = 24 for group
      1) with a 7-day 200 mg daily dose (n = 26 for group 2) of itraconazole. Clinical
      signs and symptoms and mycologic evaluation (potassium hydroxide preparation and
      Wood's lamp) were performed before treatment, and at weeks 3 and 6 after
      treatment. RESULTS: Both regimens of itraconazole were effective. Our results
      showed that there were no significant differences in efficacy and safety between
      the two treatment regimens (chi-square tests, p > 0.05). CONCLUSIONS: On the
      basis of these findings, a single dose of itraconazole 400 mg/day was as
      effective as the 7-day 200 mg daily dose in the treatment of pityriasis
      versicolor.

PMID- 12060507
TI  - Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot
      study.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a heparin-binding protein with
      mitogenic, motogenic and morphogenic activities for various cell types. The
      regenerative properties of HGF have been the object of several animal and in
      vitro studies in recent years. OBJECTIVE: To investigate the physiological and
      therapeutic effects of HGF on chronic leg ulcers. METHODS: HGF in gel form was
      locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11
      elderly patients. All patients had previously been treated by conventional
      methods and their leg ulcers had been in stable conditions for between 1 and 14
      years. Any signs of allergy, discomfort or pain were reported daily.
      Microcirculation perfusion in the ulcers, compared to the intact contiguous skin,
      was determined by laser Doppler at the beginning of the study, after 1 week and
      again after 3 months (in seven patients). Ulcer size and characteristics were
      also documented. RESULTS: It was observed that microcirculatory perfusion, which
      might reflect the angiogenic effect of HGF, was statistically significantly
      correlated (r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers.
      Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight
      out of 11 patients. No control group was included in this pilot study, which must
      be completed by proper control studies. CONCLUSION: This study suggests that HGF
      may heal chronic leg ulcers, possibly by improving the microcirculation. Proper
      control studies need to be performed.

PMID- 12060508
TI  - Necrobiotic xanthogranuloma with lambda paraproteinemia: case report of
      successful treatment with melphalan and prednisone.
AB  - BACKGROUND: Necrobiotic xanthogranuloma (NXG) is a rare non-X histiocytosis with
      conspicuous lesions on the periorbital skin. METHODS: A diabetic patient
      presented with NXG and a previous diagnosis of necrobiosis lipoidica on the legs
      over a period of almost 2 years before the development of the typical lesions of
      NXG on the periorbital regions, back, thighs and legs. The patient was found also
      to have developed lambda paraproteinemia. RESULTS: Treatment with melphalan and
      prednisone resulted in great improvement of cutaneous lesions and paraproteinemia
      remission. CONCLUSION: This case report details how melphalan and prednisone can
      be administered in the successful treatment of necrobiotic xanthogranuloma with
      lambda paraproteinemia.

PMID- 12060509
TI  - Botulinum toxin treatment for a compensatory hyperhidrosis subsequent to an upper
      thoracic sympathectomy.
AB  - BACKGROUND: Compensatory hyperhidrosis is the commonest complication of
      sympathectomy, but there's no known effective treatment. METHODS: Botulinum toxin
      type A (a total dose of 300 MU, 1.0 MU/cm(2)) was used successfully to treat a 68
      year-old male with a 5-year history of compensatory hyperhidrosis of the anterior
      chest following thoracic sympathectomy for palmar hyperhidrosis. RESULTS: The
      hyperhidrosis resolved for 8 months without systemic side effects. CONCLUSION:
      Intracutaneous injection of botulinum toxin is a fast, safe, effective and well
      accepted approach for treatment of compensatory hyperhidrosis.

PMID- 12060511
TI  - The advantages of aminolevulinic acid photodynamic therapy in dermatology.
AB  - Photodynamic therapy (PDT) is being increasingly employed in the detection and
      treatment of malignant and non-malignant disease. This local technique uses a
      photosensitizing drug activated by light to generate cell death via the
      production of reactive oxygen species. This review describes the fundamental
      processes behind PDT, focussing on the use of 5-aminolevulinic acid (ALA). ALA
      itself is not a photosensitizing drug, but administration of exogenous ALA
      induces the build-up of the natural endogenous photosensitizer protoporphyrin IX
      (PpIX). This form of PDT has proved promising for the treatment of a number of
      dermatological indications. An overview of these current and potential
      applications of ALA-based PDT is presented, with emphasis on the advantages of
      the technique that make it especially suitable for skin conditions and the
      problem areas on which future research should be focussed.

PMID- 12060512
TI  - Non-oncologic indications for ALA-PDT.
AB  - Topical photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is a well
      established treatment regimen for superficial epithelial skin tumours, but it is
      evident that inflammatory diseases of the skin and virus-induced lesions can also
      profit from PDT. Depending on the light dose applied, either cytotoxic effects
      resulting in tumour destruction or immunomodulatory effects resulting in
      improvement of inflammatory conditions occur. Patients with localized scleroderma
      that had been unresponsive to various treatments, including PUVA or bath-PUVA
      therapy, respond very well to topical ALA-PDT performed repeatedly. In contrast
      to PUVA therapy, no carcinogenic potential is being discussed for PDT. Also, HPV
      induced skin lesions might provide a possible indication for topical ALA-PDT. The
      rapidly proliferating cells in viral acanthomas accumulate ALA-induced
      protoporphyrin IX (PPIX) selectively when compared to the surrounding non
      infected cells. The efficacy of topical ALA-PDT in the treatment of recalcitrant
      foot and hand warts has been shown in a placebo-controlled, randomized, double
      blind trial. Furthermore, case reports describe a good response of other virus
      induced diseases, for example condylomata acuminata and epidermodysplasia
      verruciformis, to topical PDT with ALA. However, controlled clinical trials are
      still needed to demonstrate more fully the effectiveness of PDT for inflammatory
      skin diseases.

PMID- 12060513
TI  - Levulan: the first approved topical photosensitizer for the treatment of actinic
      keratosis.
AB  - Actinic keratosis (AK) is a very common skin problem found in patients over 50
      years of age, representing an in situ keratinocytic neoplasm that can progress to
      invasive squamous cell carcinoma of the skin. One Food and Drug Administration
      approved treatment for AK of the face and scalp is photodynamic therapy (PDT)
      with 20% aminolevulinic acid (ALA). This advanced technology has been
      demonstrated in clinical trials to be effective and well tolerated by patients.

PMID- 12060514
TI  - The emerging role of 5-ALA-PDT in dermatology: is PDT superior to standard
      treatments?
AB  - Several open studies report the efficacy of topical photodynamic therapy (PDT) in
      the treatment of non-melanoma skin cancer and pre-cursor lesions. For a new
      therapy to change clinical practice, comparison studies with standard therapies
      are required, assessing efficacy, adverse events and cosmetic outcome. This
      review considers the evidence for using topical PDT over standard therapies in
      non-melanoma skin cancer. Limited data indicates topical PDT to be superior to
      cryotherapy and equivalent to topical 5-fluorouracil in clearing non
      hyperkeratotic actinic keratoses, and to achieve a superior cosmetic outcome.
      Topical PDT is superior to topical 5-fluorouracil, and equivalent to cryotherapy,
      in the treatment of squamous cell carcinoma in situ (Bowen's disease), again with
      fewer adverse reactions. Similarly, PDT is as effective as cryotherapy for basal
      cell carcinoma, but with superior healing and cosmesis. PDT may be particularly
      advantageous for large and/or multiple lesions and for those in sites where
      disfigurement or poor healing from conventional therapies is a particular risk.
      There remains a lack of comparison data concerning routine surgery, curettage,
      and radiotherapy, but topical PDT would appear as effective as, and in certain
      aspects superior to, standard therapies in the treatment of non-melanoma skin
      cancer.

PMID- 12060515
TI  - Dryness.

PMID- 12060516
TI  - Children's health promotion through caregiver preparation in pediatric brain
      injury settings: compensating for shortened hospital stays with a three-phase
      model of health education and annotated bibliography.
AB  - Shorter hospital and rehabilitation stays in cases of pediatric brain injury
      necessitate greater preparation and training of family caregivers, who often will
      be responsible for complex and continued care at home. At the same time, a
      growing nursing shortage results in less available time for individualized, one
      on-one caregiver education in medical settings prior to discharge. What is needed
      are innovative models of caregiver preparation and education that are
      comprehensive, systematic, and maximize the use of health professionals' limited
      time. The model presented here aims to provide a progressive three-phase model of
      caregiver education that makes efficient use of health professionals' time and
      delivers crucial information in a time-released manner throughout the entire
      continuum of care under the guidance of health professionals. An annotated
      bibliography of published caregiver education resources and the appropriate time
      for their delivery to family members is provided in the Appendix.

PMID- 12060517
TI  - Perceived and performed infant care competence of younger and older adolescent
      mothers.
AB  - The investigators examined differences in perceived and performed infant care
      competence for younger (less than 17 years of age) and older (17 to 19 years of
      age) adolescent mothers. Associations were tested between perceived infant care
      competence measured at several time points and performed mothering at 12 to 18
      months infant age. A convenience sample of 78 adolescent mothers was recruited
      from two major teaching hospitals in Winnipeg, Canada. The Infant Care
      Questionnaire (ICQ), a self-report measure of infant care ability, was completed
      during the 3rd trimester and the 1st and 4th postnatal weeks. Performed mothering
      was assessed with Caldwell's HOME scale administered in the adolescent mother's
      home when the infant was 12 to 18 months old. Significant increases in competence
      perceptions over time were demonstrated for both ICQ subscales, the Mom&Baby,
      F(2, 47) = 22.73, p = 0.000, and Emotionality, F(2, 47) = 43.16, p = 0.000. This
      increase in infant care competence mirrors the maternal role competence
      trajectory reported in studies with older mothers. While no significant age group
      differences were found for Mom&Baby or Emotionality, older adolescent mothers
      were rated significantly higher on one of the HOME subscales, Variety in Daily
      Stimulation, t(n = 45), = 2.12, p =.04, and a second approached significance,
      Responsiveness, t(n = 45) = 1.86, p =.07. Pearson correlations between the
      Mom&Baby and Emotionality and the HOME subscales, Responsiveness and Environment,
      ranged between -0.30 and -0.37. Future research is required to further explain
      the negative correlations between perceived and performed infant care competence,
      establish clinical validity of self-report methods with adolescent mothers, and
      assess the influence of social, cultural, and economic factors not considered in
      this study.

PMID- 12060518
TI  - Grandparents of children with developmental disabilities: perceptions, beliefs,
      and involvement in their care.
AB  - This exploratory study evaluated the perceptions and beliefs of grandparents
      regarding their grandchild with a developmental disability and their involvement
      in his/her care and the impact of the child's disability on their lives and on
      their relationship between them. The sample included 16 grandparents of children
      with a severe developmental disability ranging in age from 5-10 who were studying
      in a special school. Data was collected by using semistructured interviews in the
      home of the grandparents. The findings indicated that grandparents' involvement
      and satisfaction with their role were a function of their attitudes towards
      disabilities in children in general and their relationship with their adult
      children, as well as their own life experiences. Their involvement with their
      grandchild with developmental disability served to strengthen the relationship
      between the grandparents. An important implication of the study is that
      professionals should plan interventions to support and encourage grandparents to
      be more involved in the care of the child with developmental disability.

PMID- 12060519
TI  - Lessons learned from providing transition services to adolescents with special
      health care needs.
AB  - This article provides insight and information about obstacles adolescents with
      special health care needs (ASHCNs) face as they progress to adulthood.
      Descriptions of these challenges are based upon clinical experiences in providing
      transition services to youth by the service coordinator seen through the Creating
      Healthy Futures transition clinic. These obstacles were classified as those
      related to health care, employment, education, independent living, social and
      recreational skills, and the service system. Information is also provided on the
      strategies project staff developed to assist youth in dealing with the challenges
      of the transition obstacles they faced.

PMID- 12060520
TI  - Comparisons of somatic action potentials from dispersed and intact rat nodose
      ganglia using patch-clamp technique.
AB  - AIM: To differentiate the electrophysiological characteristics of somatic action
      potentials (AP) from isolated Neo and Juv nodose sensory neurons (NSN) and those
      from slices of intact Juv and adult rat nodose ganglia. METHODS: For isolated
      cell recordings nodose ganglia from 3-8 d old Neo and 4 weeks old Juv rats were
      dissociated using trypsin and collagenase, respectively. Nodose ganglia slices
      with attached vagus were prepared using a sequential treatment of collagenase and
      trypsin for both Juv and adult rats. Conduction velocity (CV) was collected by
      vagal stimulation. Whole-cell patch was applied for somatic AP recordings.
      RESULTS: (1) 281 NSN from both isolated cells and nodose slices were studied.
      Across all age groups, there was no difference observed among either C- or A
      types. The difference between C- and A-type was significant. (2) Neurons
      exhibiting AP with prominent repolarization hump, broader APD50 (>2.0 ms),
      upstroke velocity at the point of APD50 (UV(APD50)) and downstroke velocity at
      the point of APD50 (DV(APD50)) below 100 V . s-1 and 50 V . s-1 were classified
      as C-type (n = 222). Those without a hump, brief APD50 (<1.0 ms), and UV(APD50)
      and DV(APD50) greater than 200 V . s-1 and 100 V . s-1 were classified as A-type
      (n = 59). (3) With slices, except for hump, APD, UV, and DV, significant
      differences were also observed (C- vs A-type) in CV from both Juv (0.56 +/- 0.15
      vs 15.6 m.s-1) and adult (0.9 +/- 0.4 vs 14.5 +/- 1.0 m . s-1) nodose slices,
      discharge rate (single or burst vs repetitive), and frequency follow (<20 Hz vs
      >100 Hz). (4) Phase analysis showed that C-type had higher AP firing threshold,
      and lower total in- and outward peak currents than A-type. CONCLUSION: C- and A
      type AP from isolated NSN of Neo or Juv rats exhibited electrophysiological
      characteristics that closely followed those of AP recorded in nodose slices.
      Therefore, isolated NSN can effectively serve as an experimental surrogate for
      electrophysiological studies of NSN requiring prior identification of afferent
      fiber type. Features of the AP wave-form such as the repolarization hump, APD50),
      and UV are strongly correlated with CV and are therefore reliable measures for
      classifying isolated NSN as either C- or A-type. It is most important that the
      nodose slice enables us to study the AP and ion channel characteristics on
      identified NSN by afferent fiber CV with adult animals.

PMID- 12060521
TI  - Norepinephrine-induced calcium mobilization in C6 glioma cells.
AB  - AIM: To investigate the mechanism underlying the norepinephrine-induced elevation
      in intracellular calcium concentration ([Ca2+]i) in C6 glioma cells. METHODS:
      Measurement of [Ca2+]i was carried out using the dual-wavelength fluorescence
      method with fura-2 as the indicator. RESULTS: Norepinephrine was found to induce
      concentration-dependent increases in [Ca2+ ]i through alpha1-adrenoreceptors. The
      [Ca2+]i elevations were extracellular-calcium independent and not influenced by
      the treatment of pertussis toxin. Pretreatments with either U73122 or
      thapsigargin abolished the subsequent cellular calcium responses to
      norepinephrine. Preincubation with phorbol 12-myristate 13-acetate (PMA)
      significantly reduce d the [Ca2+]i elevations, while protein kinase C inhibitors
      Ro31-8220 or GF-109203X completely blocked the inhibitory action of PMA. However,
      drugs either activating or inhibiting the function of protein kinase A had no
      effect on the [Ca2+]i elevations. CONCLUSION: Norepinephrine induces calcium
      mobilization from internal stores by activation of phospholipase C in C6 cells.
      The [Ca2+]i elevation is negatively regulated by the activation of protein kinase
      C.

PMID- 12060522
TI  - Arachidonate CYP hydroxylases of kidney contribute to formation of hypertension
      and maintenance of blood pressure.
AB  - AIM: To investigate the relationship of kidney-specific expression of cytochrome
      P-450 (CYP) 4A1 and the blood pressure. METHODS: The specific sense and antisense
      CYP4A1 cDNA was administered respectively with the help of eukaryotic expression
      vector pcDNA3.1 to the Sprague-Dawley (SD) rats via sublingual vein (2 mg/kg).
      The systolic blood pressure of rats was assessed by the tail- cuff method, and
      the relative tissue expression of CYP4A1 was analyzed by Western blot and
      Northern blot at RNA and protein levels in the brain, heart, lung, liver, and
      kidney of control, sense, and anti-sense CYP4A1 cDNA-treated rats. RESULTS: Two
      weeks after the injection of the sense and antisense CYP4A1 cDNA recombinants
      respectively, the mean systolic pressure of the transgenic rats increased by 1.8
      kPa +/- 0.3 kPa (13.2 mmHg +/- 2.5 mmHg) or decreased by 1.7 kPa +/- 0.3 kPa
      (13.0 mmHg +/- 2.2 mmHg) compared with control. At the levels of transcription
      and translation, the Northern and Western blots all demonstrated that CYP4A1
      preferentially overexpressed in the kidney. CONCLUSION: The administration of
      sense and antisense CYP4A1 cDNA induced hypertension and hypotension,
      respectively, which indicated that renal arachidonate hydroxylase contributed to
      the formation of hypertension and maintenance of blood pressure in normotensive
      rats.

PMID- 12060523
TI  - Effects of "Chinese yam" on hepato-nephrotoxicity of acetaminophen in rats.
AB  - AIM: To study the effect of yam in Taiwan, which is a commonly used Chinese
      medicine, on hepato-nephro-toxicity in rats. METHODS: Crude water extract of yam
      (Dioscorea alata L), was used to treat rats with an acute toxicity induced by
      acetaminophen (APAP) challenge. RESULTS: The pharmacological and biochemical
      studies showed the extract of yam had the effect of kidney secureness and liver
      fortification (P < 0.01). The pathologic sections showed good improvements in
      renal tubular degranulation changes, necrosis and disintegration. The extract of
      yam also possessed a good protection against the inflammation of central vein and
      necrosis of liver tissue. CONCLUSION: The liver and kidneys are originated from
      the same source. Pathologically, deficiency of the life essence in the kidney may
      lead to the blood deficiency in the liver. The results showed that the yam could
      prevent the damages of the liver and kidneys, thus preserving their functions.
      This could b e the reason why the yam was commonly used in traditional Chinese
      medicine, as seen in Liuwei Dihuang Wan be used in the case of deficiency of
      liver-yin and kidney-yin.

PMID- 12060524
TI  - Effects of recombinant staphylokinase on coronary thrombosis in Chinese
      experimental miniature swine.
AB  - AIM: To study the effects of recombinant staphylokinase (r-Sak) on coronary
      thrombosis, cardiac ischemia, and myocardial infarction in Chinese experimental
      miniature swine. METHODS: Endarterium was injuried and coronary thrombi were
      formed gradually through direct electrical stimulation on the coronary artery of
      Chinese experimental miniature swine. Effects of r-Sak in vitro were studied
      through coronary pathological section, microkinematography, multi media graphic
      analysis, epicardial electrogram mapping, myocardium histo chemical stain, serum
      creatine phosphokinase (CPK), and hemorheology. RESULTS: r-Sak showed a
      remarkable effect on coronary thrombus. Compared w ith the control group, the two
      dosage groups, r-Sak 0.45 mg/kg and 1.35 mg/kg, reduced the transverse section
      area of coronary thrombus (P<0.01), lessened the degree and range of cardiac
      ischemia (P<0.01), decreased the myocardial infarction area (P<0.01), the
      activity of CPK and blood viscosity (P<0.05), restrained platelet adhesion and
      aggregation, and reduced fibrinogen concentration (P<0.05). CONCLUSION: r-Sak
      could dissolve coronary thrombus obviously and lessen the pathologic reaction of
      myocardium.

PMID- 12060526
TI  - 5-Hydroxytryptamine enhances L-type calcium current in norepinephrine-induced
      hypertrophic ventricular myocytes.
AB  - AIM: To study the effects of 5-hydroxytryptamine (5-HT) on L-type calcium current
      (ICa) in norepinephrine (NE)-induced hypertrophic ventricular myocytes. METHODS:
      Left ventricular hypertrophy was induced by injecting NE intraperitoneally in
      rats. The single myocytes were isolated enzymatically from left ventricle. ICa
      was recorded with the whole-cell configuration of the patch-cl amp technique.
      RESULTS: (1) The ratio of left heart weight to body weight (LHW/BW) was higher (P
      < 0.01) in the NE-treated rats compared with the control rats on d 15. LHW/BW was
      increased 31.8 % in NE-treated rats. (2) ICa was larger in hypertrophic cells
      than that in normal cells (4.5 p A/pF +/- 0.5 pA/pF vs 3.5 pA/pF +/- 0.3 pA/pF,
      respectively, at testing potential of 0 mV; P < 0.01). (3) 5-HT (1, 10
      micromol/L) increased ICa and decreased the peak current potential from 0 mV to 
      10 mV in both myocytes. The augmentation of ICa induced by 5-HT was larger in
      hypertrophic ones. (4) 5-HT did not markedly influence the steady-state
      activation kinetics. However, 5-HT shifted steady-state inactivation curve with
      half inactivation voltage V 1/2 changing from -39.5 mV +/- 1.8 mV to -27.8 mV +/-
      1.7 m V (P < 0.05), while not changing the voltage responsiveness of calcium
      channel (slope factor k was not changed markedly). CONCLUSION: 5 -HT increased
      ICa in ventricular myocytes by changing the kinetics of steady-st ate
      inactivation. A larger alteration of ICa induced by 5-HT i n hypertrophic
      ventricular myocytes suggests that 5-HT be more prone to induce arrhythmia in
      hypertrophic heart than in normal one.

PMID- 12060525
TI  - Probucol inhibits oxidized-low density lipoprotein-induced adhesion of monocytes
      to endothelial cells in vitro.
AB  - AIM: To investigate the mechanism by which probucol (PBC) affected adhesion of
      monocytes to human umbilical vein endothelial cells (HUVEC). METHODS: Effects of
      PBC on expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell
      adhesion molecule-1 (VCAM-1), P-selectin, a nd E-selectin in human umbilical vein
      endothelial cells were examined. Moreover, the inhibitory effect of PBC were
      compared with that of monoclonal antibodies (mAbs) to ICAM-1, VCAM-1, P-selectin,
      and E-select in on adhesion induced by oxidized-low density lipoprotein(Ox-LDL).
      RESULTS: PBC at 10 to 80 micromol/L inhibited Ox-LD L-induced adhesion index from
      16.7 % to 7.0 % (P < 0.01) and Ox-LDL-induced expression of ICAM-1 (75 %) and P
      selectin (72 %). mAbs to ICAM -1 or P-selectin, when used alone, could only
      slightly reduce the adhesion of monocyte to HUVEC. When both monoclonal
      antibodies were used in combination, the adhesion was markedly inhibited from
      16.7 % to 11.3 % (P < 0.01), but the effect was still weaker than that of PBC
      (average 9.3 %). CONCLUSION: PBC exerts its inhibitory effect on the adhesion of
      monocyte to HUVEC by inhibiting the expression of ICAM-1 and P-selectin.

PMID- 12060528
TI  - Effect of Misgurnus anguillicaudatus polysaccharide on immune responses of
      splenocytes in mice.
AB  - AIM: To investigate the effect of Misgurnus anguillicaudatus polysaccharides
      (MAP) on immune responses of splenocytes in mice. METHODS: T lymphocyte
      proliferation (TLP) was measured by [3H]thymidine incorporation assay. Cytotoxic
      T lymphocyte (CTL) cytotoxicity and natural killer (NK) activity were determined
      by release of radioactive chromium [51Cr] from pre-labeled target cells. RESULTS:
      MAP 5 and 10 mg . kg-1 . d-1, ip for 7 d, could increase TLP, enhance the
      cytotoxicity of CTL and NK cells, and antagonize the effect of concanavalin A
      (ConA) on TLP suppressed by cyclophosphamide (CP). Inhibitory rates of CTL
      cytotoxicity were decreased from 51.4 % in CP control mice to 18.2 % and 35.1 %
      in MAP-treated CP mice, respectively. Furthermore, administration of MAP 10 and
      20 mg . kg-1 . d-1, ip for 7 d, restored the reduced NK cell cytotoxicity caused
      by CP administration in mice. CONCLUSION: MAP has protective effect on augmenting
      T-cell-mediated immunity and NK activity in normal and CP-treated mice.

PMID- 12060527
TI  - Inhibition of Na+/Ca2+ exchange by hexapeptide FRCRSFa in rat ventricular
      myocytes.
AB  - AIM: To study the effect of Phe-Arg-Cys-Arg-Ser-Phe-CONH2 (FRCRSFa) on Na+/Ca2+
      exchange and its specificity in rat ventricular myocytes. METHODS: Na+/Ca2+
      exchange current (INa+/Ca2+) and other currents were measured using whole-cell
      voltage clamp technique. RESULTS: A concentration-dependent inhibition of
      hexapeptide FRCRSFa on Na +/Ca2+ exchange was observed in rat ventricular
      myocytes. IC50 of inward and outward INa+/Ca2+ were 2 and 4 micromol/L,
      respectively. FRCRSFa 5 micromol/L did not affect L-type Ca2+ current, voltage
      gated Na+ current, transient outward K+ current, and inward rectifier K+ current.
      CONCLUSION: These data indicate that FRCRSFa is an available inhibitor of
      Na+/Ca2+ exchange with relative selectivity and m ay be valuable for studies of
      the Na+/Ca2+ exchange in cardiac myocytes.

PMID- 12060529
TI  - Effects of Coriolus versicolor polysaccharide B on monocyte chemoattractant
      protein 1 gene expression in rat.
AB  - AIM: To investigate the effect of Coriolus versicolor polysaccharide B (CVPS-B),
      a new water-soluble component of polysaccharides from the fungus Coriolus
      versicolor (Fr) L on monocyte chemoattractant protein-1 (MCP-1) gene expression
      in rat splenocytes. METHODS: Expression of MCP-1 mRNA in rat splenocytes was
      examined by reverse transcription-polymerase chain reaction (RT-PCR) with beta-
      actin as an internal standard. Sequencing of RT-PCR products was performed to
      confirm their specificity in MCP-1 gene composition. RESULTS: (1) Without pre
      treatment of lipopolysaccharide (LPS), the relative MCP-1 mRNA expression ratios
      (MCP-1/beta-actin) for the saline control group and for CVPS-B groups in 3
      different doses (10, 20, and 30 mg . kg-1 . d-1, ip, for 4 d) were 1.4 +/- 0.3,
      1.6 +/- 0.4, 1.7 +/- 0.5, and 1.5 +/- 0.4, respectively (P > 0.05); (2) LPS (10
      microg . kg-1, ip) enhanced the expression of MPC-1 mRNA by the ratio of 114 %;
      (3) pre-treatment with CVPS-B of 4 different doses (5, 10, 30, and 50 mg . kg-1 .
      d-1, ip, for 4 d) decreased the LPS induced expression of MPC-1 mRNA by the
      ratios of 51 %, 70 %, 84 %, and 99 %, respectively (n = 6). CONCLUSION: In a dose
      related fashion, CVPS-B inhibited the expression of MCP-1 mRNA induced by LPS in
      the rat splenocytes, but did not significantly affect the expression of MPC-1
      mRNA in the normal rat.

PMID- 12060530
TI  - Function and mechanism of pyronaridine: a new inhibitor of P-glycoprotein
      mediated multidrug resistance.
AB  - AIM: To study the effect and mechanism of pyronaridine (PND) on the reversal of
      multidrug resistance (MDR) in K562/A02 and MCF7/ADR cell lines with mdr1+.
      METHODS: MTT assay was used to determine the cells growth inhibition after
      incubation for 72 h in the presence of doxorubicin (DOX) with or without PND.
      Intracellular accumulation of DOX was analyzed by spectrofluorometry. P
      glycoprotein (P-gp) activity was investigated by measuring the extrusion of the
      cationic dye rhodamine 123 (Rh123). The apoptosis of cells and mdr1 gene
      expression were detected using flow cytometry and RTPCR, respectively. RESULTS:
      PND slightly inhibited the growth of MDR human leukemia, breast cancer cells, and
      their parental cell lines. The IC50 of PND were 5.10 - 18.66 micromol/L depending
      on the kinds of cell lines. PND at low toxic concentrations enhanced
      antiproliferative effect of DOX on MDR cells and the apoptosis induced by DOX in
      a concentration-dependent manner. Intracellular accumulation of DOX and Rh123 in
      MDR cell lines increased after combination with PND. PND did not down-regulate
      mdr1 gene expression in MDR cell lines K562/A02 and MCF7/ADR. CONCLUSION: As the
      third-generation Pgp inhibitor, PND significantly reversed MDR in MDR cell lines
      K562/A02 and MCF7/ADR by inhibiting P-gp function.

PMID- 12060531
TI  - Pharmacokinetics of leflunomide in Chinese healthy volunteers.
AB  - AIM: To study the pharmacokinetics of leflunomide in Chinese healthy volunteers.
      METHODS: A single (20, 40, and 60 mg) and 30-d -repeated (20 mg/d) oral doses of
      leflunomide were performed on 18 (12 males and 6 females) and 6 (4 males and 2
      females) Chinese healthy volunteers respectively. A771726, the active metabolite
      of leflunomide, in serum was determined by high performance liquid chromatography
      (HPLC). Data were analyzed by a 3p97 program on a Legend computer. RESULTS: Serum
      concentration curves of A 771726 in single and repeated oral administration of
      leflunomide conformed to one compartment model of the first order absorption.
      Leflunomide was absorbed rapidly with T1/2,ka of between 1.15 h and 2.23 h in
      single oral administration. The major pharmacokinetic parameters of A771726 in
      20, 40, and 60 mg groups were T1/2,ke(h): 211 +/- 18, 170 +/- 24, 252 +/- 26;
      Tmax(h): 13 +/- 12, 13 +/- 4, 9 +/- 5; Cmax (mg/L): 2.0 +/- 0.5, 5.2 +/- 0.6, 6.7
      +/- 1.5; AUC (mg . h . L-1): 647 +/- 137, 1344 +/- 191, 2555 +/- 907,
      respectively. In repeated oral administration, steady stat e concentration was
      achieved within 30 d. The mean trough concentration was between 32.0 mg/L and
      39.7 mg/L. The Cmax, Tmax, AU C0- 24 were (41.5 +/- 2.4) mg/L, (307 +/- 75) h,
      and (22099 +/- 1234) mg . h . L-1, respectively. CONCLUSION: The absorption of
      leflunomide was rapid, and it s elimination was slow after oral administration.
      The pharmacokinetic results showed that it exhibited first order kinetic
      characteristics.

PMID- 12060532
TI  - Inhibitory effect and its kinetic analysis of tyrphostin AG1478 on recombinant
      human protein kinase CK2 holoenzyme.
AB  - AIM: To study the direct effect of tyrphostin AG1478 [4-(3-chloroanilino)-6,7
      dimethoxyquinazoline] on recombinant human protein kinase CK2 holoenzyme and its
      kinetics. METHODS: Recombinant human protein kinase CK2 alpha and beta subunits
      were mixed at equal molar ratio and CK2 holoenzyme were reconstituted. The CK2
      activity was assayed by detecting incorporation of [gamma-32P]ATP or [gamma
      32P]GTP into substrates in various conditions. RESULTS: These results
      demonstrated that the recombinant human CK2 was a second messengers (Ca2+, cAMP,
      and cGMP)-independent protein kinase, the characterization and function of the
      reconstituted holoenzyme were consistent with those of native CK2. AG1478
      strongly inhibited the holoenzyme activity of recombinant human protein kinase
      CK2 with IC50 of 25.9 micromol/L, the inhibition is very close to that of N-(2
      aminoethyl)-5-chloronaphthalene-1-sulfonamide (A3), but less potent than that of
      5,6-dichloro-1- beta-D-ribofuranosylbenzimidazole (DRB), known as CK2 special
      inhibitors with IC50 of 25.5 micromol/L and 10.4 micromol/L respectively. Kinetic
      studies of AG1478 on recombinant human CK2 showed that inhibitions were
      competitive with both GTP and casein, thus AG1478 was as bisubstrate inhibitor.
      CONCLUSION: The present study indicates that AG1478 is not only an effective
      inhibitor of protein tyrosine kinases of epidermal growth factor receptor (EGFR),
      but also a novel potent inhibitor of protein kinase CK2. The recombinant human
      protein kinase CK2 might be used as a molecular target for simpler screening and
      development of more effective inhibitors of CK2.

PMID- 12060533
TI  - Cytotoxicity of flutamide and 2-hydroxyflutamide and their effects on CYP1A2 mRNA
      in primary rat hepatocytes.
AB  - AIM: To compare the cytotoxicity of flutamide and its active metabolite 2
      hydroxyflutamide and their effects on cytochrome P-450 1A2 mRNA in primary rat
      hepatocytes. METHODS: After the isolation of hepatocytes a nd t he primary
      incubation for 4 h, flutamide and 2-hydroxyflutamide were added respectively to
      the medium at the concentration of 10, 20, and 50 mg/L and incubated for 8 h.
      Cytotoxicity of hepatocytes was assessed by Trypan blue exclusion, lactate
      dehydrogenase (LDH) leakage, percentage of alanine aminotransferase (ALT) or
      aspartate aminotransferase (AST) release, and reduced glutathione (GSH). The
      effect of flutamide and 2-flutamide on the CYP1A2 mRNA level was further analyzed
      by Northern blot. RESULTS: After incubation for 8 h, cell viability was observed
      by Trypan blue exclusion. The increase of ALT and AST activity and the decrease
      of glutathione content were also noted at 10, 20, and 50 mg/L of flutamide and 50
      mg/L of 2-hydroxyflutamide as compared with normal rat hepatocytes. Induction of
      CYP1A 2 mRNA were 2-, 5-, and 7.5-fold at 10, 20, and 50 mg/L of flutamide and
      3.5-fold at 50 mg/L of 2-hydroxyflutamide. CONCLUSION: Cytotoxicity of flutamide
      and its effect on CYP1A2 mRNA were stronger than those of its active metabolite 2
      hydroxyflutamide in primary rat hepatocytes.

PMID- 12060535
TI  - Assessment of estrogenic activity of natural compounds using improved E-screen
      assay.
AB  - AIM: To improve E-screen assay and make it more accurate to screen estrogenic
      compounds. METHODS: Estrogen receptor antisense RNA expression plasmid (pCASER)
      was constructed and introduced into MCF-7 with lipofectAMINE(TM), and positive
      clones were screened out with G418. PCR amplification was employed to identify
      whether estrogen receptor (ER) cDNA fragment had been inserted into MCF-7 cell
      genomes. Western blot was applied to detect the expression of ER. Cell growth was
      determined by MTT assay. RESULTS: One ER antisense clone (MTASER) had been
      screened out. The effects of 17beta-estradiol, genistein, droloxifen, miyabenol
      C, and kobophenol A on MCF-7 were stronger than those effects on MTASER.
      Epidermal growth factor (EGF) had equivalent stimulatory effects on the
      proliferation of MCF-7 and MTASER. CONCLUSION: The improved E-screen assay could
      screen estrogenic compounds more accurately than original E-screen assay did.

PMID- 12060534
TI  - Genotype of CYP3AP1 associated with CYP3A activity in Chinese Han population.
AB  - AIM: To investigate the distribution of genotype of CYP3AP1 in Chinese Han
      population and the correlation with CYP3A activity. METHODS: Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in
      CYP3AP1 genotype analysis; using midazolam as probe drug, CYP3A activity of 191
      Chinese healthy subjects was measured by plasma 1'-hydroxymidazolam/midazolam (1'
      OH-MDZ/MDZ) ratio at 1 h after oral administration of 7.5 mg midazolam. RESULTS:
      There was significant difference of CYP3A activity in different genotypes of
      CYP3AP1 in vivo (P <0.05). The activity of CYP3A in homozygous A(-44)
      (CYP3AP1*3/CYP3AP1*3) is lower than heterozygous A(-44)G (CYP3AP1*1/CYP3AP1*3),
      and the CYP3A activity in homozygous G(-44) (CYP3AP1*1/CYP3AP1*1) is t he
      highest. CONCLUSION: There was association between the genotype of CYP3AP1 and
      increased activity of CYP3A in vivo.

PMID- 12060536
TI  - [Virtues and defects of the projector "canyon"].

PMID- 12060537
TI  - [Tuberculosis in the Zaragoza province. Estimation by means of the capture
      recapture method].
AB  - INTRODUCTION: Tuberculosis (TB) is an underreported condition to the Communicable
      Diseases Control System (CDCS). The objective of this work was to estimate the
      actual incidence of tuberculosis and the epidemiological characteristics of the
      diseases in the Zaragoza province. MATERIAL AND METHODS: Retrospective study in
      which the capture-recapture method was used to estimate the number of
      tuberculosis cases, by using the microbiology laboratories and the CDSC as data
      sources. The socio-demographic and clinical characteristics of diagnosed patients
      throughout three years in this province were analyzed. RESULTS: The mean annual
      incidence rate of TB was 22.02 per 100,000 inhabitants according to
      microbiological data, and 48.5 per 100,000 according to the capture-recapture
      method. A total of 569 patients were studied, and 400 of them were males (70.3%).
      The mean age was 43.2 years, and the 25-34 year-old group had the highest number
      of cases (27.9%). Twenty-three percent of cases were co-infected with HIV, and
      77.4% were parenteral drug abusers, and 4.4% immigrants. CONCLUSIONS: The capture
      recapture method has demonstrated to be useful to know the relevance of TB in our
      setting. The actual incidence of tuberculosis was higher than that pointed out by
      the CDCS. Relevant differences were observed regarding incidence rates by age and
      sex groups. HIV infection and immigration do not appear to explain the frequency
      of this disease in our setting.

PMID- 12060538
TI  - [Hypertensive crises: prevalence and clinical aspects].
AB  - OBJECTIVE: To analyze the prevalence and characteristics of patients with
      hypertensive crises and to know the clinical differences between patients with
      hypertensive urgencies and patients with hypertensive emergencies. PATIENTS AND
      METHODS: Three-months prospective study in which all patients attended at the
      Emergency Department with an hypertensive crisis (arterial blood pressure of at
      least 210/120 mmHg) were included. From each patient, a clinical history,
      physical examination, eye fundus examination, blood analysis, electrocardiogram,
      and a chest X-ray were obtained. RESULTS: A total of 118 patients were included
      in the study, representing 0.65% of all attended emergencies. Twenty-two percent
      of them had an emergency hypertensive crisis. Coronary heart disease was the most
      common cause for this emergency crisis. Hypertension was unknown to 12.7% of
      patients and 12.6% of patients aware of their condition were not taking any
      medication. Twenty-four percent of patients were diabetic. Patients with
      hypertensive emergencies had more involvement of target organs. Twenty-four
      percent of crises resolved with no therapy, and captopril was the most commonly
      used drug. CONCLUSIONS: Hypertensive crises accounted for 0.65% of attended
      emergencies at our institution. Coronary heart disease was the most common
      condition for hypertensive emergencies. Patients with hypertensive emergencies
      had a more severe involvement of target organs. Twenty four percent of crisis
      resolved with rest alone.

PMID- 12060539
TI  - [Analysis of mutations in genes BRCA1 and BRCA2 among patients with breast and
      ovarian cancer in northern Portugal and Galicia].
AB  - OBJECTIVE: To detect mutations in the BRCA1 and BRCA2 genes by means of the
      protein truncation test (PTT) in a population in northern Portugal and Galicia
      with breast and ovarian cancer. DESIGN: Prospective study. SETTING: Patients in
      northern Portugal and Galicia with family history of breast and/or ovarian
      cancer.Patients. A total of 76 women with family history of breast cancer
      according to the BCLC criteria (Breast Cancer Linkage Consortium) were studied at
      IPATIMUP. MAIN RESULTS: Five cases (6.5%) with changes in the normal sequence in
      genes BRCA1 and BRCA2 were identified; three of these mutations occurred in the
      gene BRCA1 and the other two in the gene BRCA2. Two out of the three mutations
      found in the gene BRCA1 were de novo mutations. Changes detected in the normal
      sequence in the gene BRCA2 were mutations reported for the first time among the
      study population, according to the information obtained through the BCIC database
      (Breast Cancer Information Core). CONCLUSIONS: This was the first study in
      detecting individuals carrying mutations in the susceptibility breast cancer
      genes BRCA1 and BRCA2 among the population of northern Portugal and Galicia.

PMID- 12060541
TI  - [Pancreatic neuroendocrine tumors: how far have we gone ahead?].

PMID- 12060540
TI  - [Cardiovascular and hormonal factors associated with the lack of nocturnal fall
      in blood pressure among individuals aged over 55].
AB  - BACKGROUND: Usually, there is a physiological fall in nocturnal blood pressure
      among all individuals, both hypertensive and normotensive individuals. The lack
      of nocturnal blood pressure (BP) fall may be associated with the risk of
      developing cardiovascular complications in hypertensive patients. Cardiovascular
      and hormonal factors associated with the lack of nocturnal blood pressure fall
      was studied in individuals aged over 55, those most exposed to this kind of
      complications. METHODS: A total of 108 individuals aged over 55 and with a wide
      range of BP (59 normotensive and 49 light-moderate hypertensive with no previous
      treatment) were studied. Two groups were established: dipper and non-dipper, with
      a fall over 10% in nocturnal SBP and DBP or not, respectively. Patients included
      in the study underwent serum hormonal measurements (renin, aldosterone,
      endoteline-1, atrial natriuretic peptide, free epinephrine and norepinephrine),
      continuous blood pressure monitoring for 24 hours (CBPM) and echocardiography
      with measurement of left ventricular mass (LVM), cardiac output, and peripheral
      vascular resistances (PVR) (determined in function of mean blood pressure and
      cardiac output). RESULTS: Fifty-one individuals were dipper and 57 were non
      dipper. Significantly higher cholesterol (p < 0.05) and free norepinephrine (p <
      0.001) levels among dipper compared with non-dipper individuals were observed.
      Non-dipper individuals had PVR significantly higher than dipper individuals (p <
      0.05). Values of diurnal BP, other hormonal measurements, and CBPM did not differ
      significantly between the two groups. CONCLUSIONS: Non-dipper individuals aged
      over 55 have lower circulating free norepinephrine values and higher peripheral
      vascular resistances than dipper individuals, irrespective of diurnal blood
      pressure values. The left ventricular mass does not differ significantly between
      the two groups.

PMID- 12060542
TI  - [Polymerase chain reaction. Basis and application in Internal Medicine].

PMID- 12060543
TI  - [Oral contraceptives and risk of vein thromboembolic disease].

PMID- 12060544
TI  - [Legal aspects of medical care to drug addicts].

PMID- 12060545
TI  - [Diagnostic and therapeutic guideline for acute confusional syndrome].

PMID- 12060546
TI  - [79-year old woman with heart failure and mediastinal widening].

PMID- 12060547
TI  - [Disabling lumbar pain in a 53-year old woman].

PMID- 12060548
TI  - [Intermittent claudication as presenting symptom of Takayasu arteritis].

PMID- 12060549
TI  - [Young woman with multiple space-occupying lesions in the central nervous
      system].

PMID- 12060550
TI  - [Reactive perforating collagenosis and colon carcinoma].

PMID- 12060551
TI  - [Interferon alpha-2b induced lupus erythematosus in a patient with chronic
      hepatitis C infection].

PMID- 12060552
TI  - [Prognostic factors of relapse in drug therapy of Graves-Basedow disease].

PMID- 12060553
TI  - [Use of Appropriateness Evaluation Protocol for the evaluation of hospital
      admission overuse].

PMID- 12060555
TI  - Metalloproteinase and growth factor interactions: do they play a role in
      pulmonary fibrosis?
AB  - Chronic lung disease due to interstitial fibrosis can be a consequence of acute
      lung injury and inflammation. The inflammatory response is mediated through the
      migration of inflammatory cells, actions of proinflammatory cytokines, and the
      secretion of matrix-degrading proteinases. After the initial inflammatory insult,
      successful healing of the lung may occur, or alternatively, dysregulated tissue
      repair can result in scarring and fibrosis. On the basis of recent insights into
      the mechanisms underlying acute lung injury and its long-term consequences, data
      suggest that proteinases, such as the matrix metalloproteinases (MMPs), may not
      only be involved in the breakdown and remodeling that occurs during the injury
      but may also cause the release of growth factors and cytokines known to influence
      growth and differentiation of target cells within the lung. Through the release
      of and activation of fibrosis-promoting cytokines and growth factors such as
      transforming growth factor-beta1, tumor necrosis factor-alpha, and insulin-like
      growth factors by MMPs, we propose that these metalloproteinases may be integral
      to the initiation and progression of pulmonary fibrosis.

PMID- 12060556
TI  - Parathyroid hormone-related protein-(38-64) regulates lung cell proliferation
      after silica injury.
AB  - Inhalation of silica leads to acute lung injury and alveolar type II cell
      proliferation. Type II cell proliferation after hyperoxic lung injury is
      regulated, in part, by parathyroid hormone-related protein (PTHrP). In this
      study, we investigated lung PTHrP and its effects on epithelial proliferation
      after injury induced by silica. Lung PTHrP decreased modestly 4 days after we
      instilled 10 mg of silica into rat lungs and then recovered from 4 to 28 days.
      The number of proliferating cell nuclear antigen (PCNA)-positive type II cells
      was increased threefold in silica-injured lungs compared with controls.
      Subsequently, rats were treated with four exogenous PTHrP peptides in the silica
      instillate, which were administered subcutaneously daily. One peptide, PTHrP-(38
      64), had consistent and significant effects on cell proliferation. PTHrP-(38-64)
      increased the median number of PCNA-positive cells/field nearly fourfold above
      controls, 380 vs. 109 (P < 0.05). Thymidine incorporation was 2.5 times higher in
      type II cells isolated from rats treated with PTHrP-(38-64) compared with PBS.
      PTHrP-(38-64) significantly increased the number of cells expressing alkaline
      phosphatase, a type II cell marker. This study indicates that PTHrP-(38-64)
      stimulates type II cell growth and may have a role in lung repair in silica
      injured rats.

PMID- 12060557
TI  - Noninvasive detection of endotoxin-induced mucus hypersecretion in rat lung by
      MRI.
AB  - Using magnetic resonance imaging (MRI), we detected a signal in the lungs of
      Brown Norway rats after intratracheal administration of endotoxin
      [lipopolysaccharide (LPS)]. The signal had two components: one, of diffuse
      appearance and higher intensity, was particularly prominent up to 48 h after LPS;
      the second, showing an irregular appearance and weaker intensity, was predominant
      later. Bronchoalveolar lavage fluid analysis indicated that generalized
      granulocytic (especially neutrophilic) inflammation was a major contributor to
      the signal at the early time points, with mucus being a major factor contributing
      at the later time points. The facts that animals can breathe freely during data
      acquisition and that neither respiration nor cardiac triggering is applied render
      this MRI approach attractive for the routine testing of anti-inflammatory drugs.
      In particular, the prospect of noninvasively detecting a sustained mucus
      hypersecretory phenotype in the lung brings an important new perspective to
      models of chronic obstructive pulmonary diseases in animals.

PMID- 12060558
TI  - Distinct patterns of apoptosis in the lung during liquid ventilation compared
      with gas ventilation.
AB  - To determine whether liquid ventilation (LV) causes less cell injury and improves
      lung function compared with conventional gas ventilation (GV), we analyzed
      pulmonary physiological profiles, lung histology, and cell death in 110- and 120
      day preterm lambs, which were randomized to receive either ventilation modality
      on FI(O(2)) = 1. LV lungs were well expanded with adequate pulmonary function,
      whereas GV animals exhibited marked atelectasis, poor pulmonary function, and
      increased mortality. Both ventilatory strategies induced marked lung cell
      apoptosis, but with distinct patterns of distribution. Although GV induced
      apoptosis of epithelium primarily in the lining and within the lumina of
      bronchioles, LV induced significant apoptosis much more homogeneously throughout
      lung parenchyma including alveoli and interstitial spaces. These studies suggest
      that although both forms of ventilation cause regional apoptosis, LV more
      effectively delivers oxygen and recruits the lung more homogeneously than GV.

PMID- 12060559
TI  - ET-1 receptor gene expression and distribution in L1 and L2 cells from
      hypertensive sheep pulmonary artery.
AB  - We examined gene and surface expression and activity of the endothelin (ET)-1
      receptors (ETA and ETB) in subendothelial (L1) and inner medial (L2) cells from
      the main pulmonary artery of sheep with continuous air embolization (CAE)-induced
      chronic pulmonary hypertension (CPH). According to quantitative real-time RT-PCR,
      basal gene expression of both receptors was significantly higher in L2 than L1
      cells, and hypertensive L2 cells showed significantly higher gene expression of
      ETB than controls. Expression of both genes in hypertensive L1 cells was similar
      to controls. Fluorescence-activated cell sorter analysis confirmed the increased
      distribution of ET(B) in hypertensive L2 cells. Although only the ETA receptors
      in control L2 cells showed significant binding of [125I]-labeled ET-1 at 1 h,
      both receptors bound ET-1 to hypertensive cells. Exposure to exogenous ET-1 for
      18 h revealed that only the L2 cells internalized ET-1, and internalization by
      hypertensive L2 cells was significantly reduced when compared with controls.
      Treatment with ETA (BQ-610) and ETB (BQ-788) receptor antagonists demonstrated
      that both receptors contributed to internalization of ET-1 in control L2 cells,
      whereas in hypertensive cells only when both receptor antagonists were used in
      combination was significant suppression of ET-1 internalization found. We
      conclude that in sheep receiving CAE, alterations in ETB receptors in cells of
      the L2 layer may contribute to the maintenance of CPH via alterations in their
      expression, distribution, and activity.

PMID- 12060560
TI  - Pulmonary type II cell hypertrophy and pulmonary lipoproteinosis are features of
      chronic IL-13 exposure.
AB  - Interleukin (IL)-13, a key mediator of Th2-mediated immunity, contributes to the
      pathogenesis of asthma and other pulmonary diseases via its ability to generate
      fibrosis, mucus metaplasia, eosinophilic inflammation, and airway
      hyperresponsiveness. In these studies, we compared surfactant accumulation in
      wild-type mice and mice in which IL-13 was overexpressed in the lung. When
      compared with littermate controls, transgenic animals showed alveolar type II
      cell hypertrophy under light and electron microscopy. Over time, their alveoli
      also filled with surfactant in a pulmonary alveolar proteinosis pattern. At the
      same time, prominent interstitial fibrosis occurs. Bronchoalveolar lavage fluid
      from these mice had a three- to sixfold increase in surfactant phospholipids.
      Surfactant proteins (SP)-A, -B, and -C showed two- to threefold increases,
      whereas SP-D increased 70-fold. These results indicate that IL-13 is a potent
      stimulator of surfactant phospholipid and surfactant accumulation in the lung. IL
      13 may therefore play a central role in the broad range of chronic pulmonary
      conditions in which fibrosis, type II cell hypertrophy, and surfactant
      accumulation occur.

PMID- 12060562
TI  - IL-13-induced Clara cell secretory protein expression in airway epithelium: role
      of EGFR signaling pathway.
AB  - Previous work showed that the Th2 cytokine interleukin (IL)-13 induces goblet
      cell metaplasia via an indirect mechanism involving the expression and subsequent
      activation of epidermal growth factor receptor (EGFR). Because Clara cell
      secretory protein (CCSP) expression has been reported in cells that express
      mucins, we examined the effect of IL-13 on CCSP gene and protein expression in
      pathogen-free rat airways and in pulmonary mucoepidermoid NCI-H292 cells.
      Intratracheal instillation of IL-13 induced CCSP mRNA in epithelial cells without
      cilia within 8-16 h, maximal between 24 and 48 h; CCSP immunostaining increased
      in a time-dependent fashion, maximal at 48 h. The CCSP immunostaining was
      localized in nongranulated secretory cells and goblet cells and in the lumen.
      Pretreatment with the selective EGFR tyrosine kinase inhibitor BIBX1522,
      cyclophosphamide (an inhibitor of bone marrow leukocyte mobilization), or a
      blocking antibody to IL-8 prevented CCSP staining. Treatment of NCI-H292 cells
      with the EGFR ligand transforming growth factor-alpha, but not with IL-13 alone,
      induced CCSP gene and protein expression. Selective EGFR tyrosine kinase
      inhibitors, BIBX1522 and AG1478, prevented CCSP expression in NCI-H292 cells, but
      the platelet-derived growth factor receptor tyrosine kinase inhibitor AG1295 had
      no effect. These findings indicate that IL-13 induces CCSP expression via an EGFR
      and leukocyte-dependent pathway.

PMID- 12060561
TI  - Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic
      lungs.
AB  - We hypothesized that exposure of murine fetuses to environmental toxins, such as
      nitrofen, during early embryogenesis alters vasculogenesis. To address our
      hypothesis, we assessed protein levels of endothelial cell-selective angiogenic
      factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and
      mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a
      transmembrane receptor tyrosine kinase. VEGF and Flk-1 proteins were lower in
      hypoplastic lungs from pseudoglandular to alveolar stages than in normal lungs at
      equivalent developmental time points significant for induction of pulmonary
      vasculogenesis and angiogenesis. ANG-1 protein was higher in hypoplastic lungs
      than in normal lungs at all the developmental stages considered in this study,
      i.e., pseudoglandular, canalicular, saccular, and alveolar stages. We assessed
      exogenous VEGF-mediated endothelial cell response on extracellular signal
      regulated kinase (ERK) 1/2, also referred to as p44/42 mitogen-activated protein
      kinase. Hypoplastic lungs had more elevated ERK 1/2 protein than normal
      developing lungs. Exposure to exogenous VEGF activated ERK 1/2 in normal
      developing lungs but not in hypoplastic lungs. Our results suggest that in
      hypoplastic lungs: 1) low VEGF signifies negative effects on
      vasculogenesis/angiogenesis and indicates altered endothelial-mesenchymal
      interactions; 2) increased ANG-1 protein may be required to maintain vessel
      integrity and quiescence; and 3) regulation of ERK 1/2 protein is affected in
      hypoplastic lungs. We speculate that extensive remodeling of blood vessels in
      hypoplastic lungs may occur to compensate for structurally and functionally
      defective vasculature.

PMID- 12060563
TI  - Surfactant protein A regulates surfactant phospholipid clearance after LPS
      induced injury in vivo.
AB  - Previous in vitro studies have suggested that surfactant protein A (SP-A) may
      play a role in pulmonary surfactant homeostasis by mediating surfactant secretion
      and clearance. However, mice made deficient in SP-A [SP-A (-/-) animals] have
      relatively normal levels of surfactant compared with wild-type SP-A (+/+)
      animals. We hypothesize that SP-A may play a role in surfactant homeostasis after
      acute lung injury. Bacterial lipopolysaccharide was instilled into the lungs of
      SP-A (-/-) mice and SP-A (+/+) mice to induce injury. Surfactant phospholipid
      levels were increased 1.6-fold in injured SP-A (-/-) animals, although injury did
      not alter [3H]choline or [14C]palmitate incorporation into
      dipalmitoylphosphatidylcholine (DPPC), suggesting no change in surfactant
      synthesis/secretion 12 h after injury. Clearance of [3H]DPPC from the lungs of
      injured SP-A (-/-) animals was decreased by approximately 40%. Instillation of 50
      microg of exogenous SP-A rescued both the clearance defect and the increased
      phospholipid defect in injured SP-A (-/-) animals, suggesting that SP-A may play
      a role in regulating clearance of surfactant phospholipids after acute lung
      injury.

PMID- 12060564
TI  - Estradiol attenuates hypoxia-induced pulmonary endothelin-1 gene expression.
AB  - The ovarian hormone 17beta-estradiol (E2beta) attenuates chronic hypoxia-induced
      pulmonary hypertension. We hypothesized that E2beta attenuates this response to
      hypoxia by decreasing pulmonary expression of the vasoactive and mitogenic
      peptide endothelin-1 (ET-1). To test this hypothesis, we measured preproET-1 mRNA
      and ET-1 peptide levels in the lungs of adult female normoxic and hypoxic (24 h
      or 4 wk at barometric pressure = 380 mmHg) rats with intact ovaries and in
      hypoxic ovariectomized (OVX) rats administered E2beta or vehicle via subcutaneous
      osmotic pumps. Hypoxic exposure increased lung preproET-1 mRNA levels in OVX
      vehicle-treated rats, but not in rats with intact ovaries. In addition, E2beta
      replacement prevented hypoxia-mediated increases in preproET-1 mRNA and ET-1
      peptide expression. Considering that hypoxic induction of ET-1 gene expression is
      mediated by a hypoxia-inducible transcription factor(s) (HIF), we further
      hypothesized that E2beta-induced attenuation of pulmonary ET-1 expression during
      hypoxia results from decreased HIF activity. We found that E2beta abolished HIF
      dependent increases in reporter gene activity. Further experiments demonstrated
      that overexpression of the transcriptional coactivator cAMP response element
      binding protein (CREB) binding protein (CBP)/p300, a factor common to both the
      estrogen receptor and HIF pathways, eliminated E2beta-mediated attenuation of
      hypoxia-induced ET-1 promoter activity. We conclude that E2beta inhibits hypoxic
      induction of ET-1 gene expression by interfering with HIF activity, possibly
      through competition for limiting quantities of CBP/p300.

PMID- 12060565
TI  - Combined SP-A-bleomycin effect on cytokines by THP-1 cells: impact of surfactant
      lipids on this effect.
AB  - Surfactant protein A (SP-A) plays a role in host defense and inflammation in the
      lung. In the present study, we investigated the hypothesis that SP-A is involved
      in bleomycin-induced pulmonary fibrosis. We studied the effects of human SP-A on
      bleomycin-induced cytokine production and mRNA expression in THP-1 macrophage
      like cells and obtained the following results. 1) Bleomycin-treated THP-1 cells
      increased tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, and IL-1beta
      production in dose- and time-dependent patterns, as we have observed with SP-A.
      TNF-alpha levels were unaffected by treatment with cytosine arabinoside. 2) The
      combined bleomycin-SP-A effect on cytokine production is additive by RNase
      protection assay and synergistic by enzyme-linked immunosorbent assay. 3)
      Although the bleomycin effect on cytokine production was not significantly
      affected by the presence of surfactant lipid, the additive and synergistic effect
      of SP-A-bleomycin on cytokine production was significantly reduced. We speculate
      that the elevated cytokine levels resulting from the bleomycin-SP-A synergism are
      responsible for bleomycin-induced pulmonary fibrosis and that surfactant lipids
      can help ameliorate pulmonary complications observed during bleomycin
      chemotherapy.

PMID- 12060566
TI  - A p38 MAPK inhibitor, FR-167653, ameliorates murine bleomycin-induced pulmonary
      fibrosis.
AB  - To elucidate the pathophysiology of pulmonary fibrosis, we investigated the
      involvement of p38 mitogen-activated protein kinase (MAPK), which is one of the
      major signal transduction pathways of proinflammatory cytokines, in a murine
      model of bleomycin-induced lung fibrosis. p38 MAPK and its substrate, activating
      transcription factor (ATF)-2, in bronchoalveolar lavage fluid cells were
      phosphorylated by intratracheal exposure of bleomycin, and the phosphorylation of
      ATF-2 was inhibited by subcutaneous administration of a specific inhibitor of p38
      MAPK, FR-167653. FR-167653 also inhibited augmented expression of tumor necrosis
      factor -alpha, connective tissue growth factor, and apoptosis of lung cells
      induced by bleomycin administration. Moreover, daily subcutaneous administration
      of FR-167653 (from 1 day before to 14 days after bleomycin administration)
      ameliorated pulmonary fibrosis and pulmonary cachexia induced by bleomycin. These
      findings demonstrated that p38 MAPK is involved in bleomycin-induced pulmonary
      fibrosis, and its inhibitor, FR-167653, may be a feasible therapeutic agent.

PMID- 12060567
TI  - Alkalosis stimulates endothelial nitric oxide synthase in cultured human
      pulmonary arterial endothelial cells.
AB  - To investigate the effect of extracellular pH on endothelial nitric oxide
      synthase (eNOS) in human pulmonary arteries, we measured eNOS activity and
      expression as well as some ion channels in human pulmonary arterial endothelial
      cells (HPAEC) exposed to various pH levels (6.6-8.0). eNOS activity was found to
      increase with alkalization and decrease with acidification, while Ca2+ uptake
      into HPAEC increased with alkalization. The addition of 3',4'-dichlorobenzamil
      hydrochloride, an inhibitor of the Na+/Ca2+ exchanger (NCX), prevented the
      increase of eNOS activity with alkalosis. Exposure to alkalosis and acidosis
      increased eNOS and NCX mRNA levels. These results suggest that an elevation of
      extracellular pH activates eNOS via the influx of extracellular Ca2+ and that NCX
      also regulates eNOS activity during alkalosis. Furthermore, NCX may have a tight
      interaction with eNOS at the level of transcription and might affect pulmonary
      circulation during alkalosis and acidosis.

PMID- 12060568
TI  - Chronic carbon monoxide enhanced IbTx-sensitive currents in rat resistance
      pulmonary artery smooth muscle cells.
AB  - Exogenous carbon monoxide (CO) can induce pulmonary vasodilation by acting
      directly on pulmonary artery (PA) smooth muscle cells. We investigated the
      contribution of K+ channels to the regulation of resistance PA resting membrane
      potential on control (PAC) rats and rats exposed to CO for 3 wk at 530
      parts/million, labeled as PACO rats. Whole cell patch-clamp experiments revealed
      that the resting membrane potential of PACO cells was more negative than that of
      PAC cells. This was associated with a decrease of membrane resistance in PACO
      cells. Additional analysis showed that outward current density in PACO cells was
      higher (50% at +60 mV) than in PAC cells. This was linked to an increase of
      iberiotoxin (IbTx)-sensitive current. Chronic CO hyperpolarized membrane of
      pressurized PA from -46.9 +/- 1.2 to -56.4 +/- 2.6 mV. Additionally, IbTx
      significantly depolarized membrane of smooth muscle cells from PACO arteries but
      not from PAC arteries. The present study provides initial evidence of an increase
      of Ca2+-activated K+ current in smooth muscle cells from PA of rats exposed to
      chronic CO.

PMID- 12060569
TI  - Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions
      of PTHrP and leptin.
AB  - Intrauterine lung development, culminating in physiological pulmonary surfactant
      production by epithelial type II (TII) cells, is driven by fluid distension
      through unknown mechanisms. Differentiation of alveolar epithelial and
      mesenchymal cells is mediated by soluble factors like parathyroid hormone-related
      protein (PTHrP), a stretch-sensitive TII cell product. PTHrP stimulates pulmonary
      surfactant production by a paracrine feedback loop mediated by leptin, a soluble
      product of the mature lipofibroblast (LF). When LFs and TIIs are stretched in
      coculture, there is a fivefold increase in surfactant phospholipid synthesis that
      can be "neutralized" by inhibitors of PTHrP or leptin, implicating a paracrine
      feedback loop in this mechanism. Stretching LFs stimulates PTHrP binding (2.5
      fold) and downstream stimulation of triglyceride uptake quantitatively (15-25%)
      due to upregulation of adipose differentiation-related protein expression.
      Stretching TII cells increases leptin stimulation of their surfactant
      phospholipid synthesis threefold, suggesting that retrograde signaling by leptin
      to TII cells is also stretch sensitive. We conclude that the effect of stretch on
      alveolar LF and TII differentiation is coordinated by PTHrP, leptin, and their
      receptors.

PMID- 12060570
TI  - Dopamine increases lung liquid clearance during mechanical ventilation.
AB  - Short-term mechanical ventilation with high tidal volume (HVT) causes mild to
      moderate lung injury and impairs active Na+ transport and lung liquid clearance
      in rats. Dopamine (DA) enhances active Na+ transport in normal rat lungs by
      increasing Na+-K+-ATPase activity in the alveolar epithelium. We examined whether
      DA would increase alveolar fluid reabsorption in rats ventilated with HVT for 40
      min compared with those ventilated with low tidal volume (LVT) and with
      nonventilated rats. Similar to previous reports, HVT ventilation decreased
      alveolar fluid reabsorption by ~50% (P < 0.001). DA increased alveolar fluid
      reabsorption in nonventilated control rats (by ~60%), LVT ventilated rats (by
      approximately 55%), and HVT ventilated rats (by ~200%). In parallel studies, DA
      increased Na+-K+-ATPase activity in cultured rat alveolar epithelial type II
      cells (ATII). Depolymerization of cellular microtubules by colchicine inhibited
      the effect of DA on HVT ventilated rats as well as on Na+-K+-ATPase activity in
      ATII cells. Neither DA nor colchicine affected the short-term Na+-K+-ATPase
      alpha1- and beta1-subunit mRNA steady-state levels or total alpha1- and beta1
      subunit protein abundance in ATII cells. Thus we reason that DA improved alveolar
      fluid reabsorption in rats ventilated with HVT by upregulating the Na+-K+-ATPase
      function in alveolar epithelial cells.

PMID- 12060571
TI  - Inhibition of endogenous TRP1 decreases capacitative Ca2+ entry and attenuates
      pulmonary artery smooth muscle cell proliferation.
AB  - Pulmonary vascular medial hypertrophy due to proliferation of pulmonary artery
      smooth muscle cells (PASMC) greatly contributes to the increased pulmonary
      vascular resistance in pulmonary hypertension patients. A rise in cytosolic free
      Ca2+ concentration ([Ca2+]cyt) is an important stimulus for cell growth in PASMC.
      Resting [Ca2+]cyt, intracellularly stored [Ca2+], capacitative Ca2+ entry (CCE),
      and store-operated Ca2+ currents (I(SOC)) are greater in proliferating human
      PASMC than in growth-arrested cells. Expression of TRP1, a transient receptor
      potential gene proposed to encode the channels responsible for CCE and I(SOC),
      was also upregulated in proliferating PASMC. Our aim was to determine if
      inhibition of endogenous TRP1 gene expression affects I(SOC) and CCE and
      regulates cell proliferation in human PASMC. Cells were treated with an antisense
      oligonucleotide (AS, for 24 h) specifically designed to cleave TRP1 mRNA and then
      returned to normal growth medium for 40 h before the experiments. Then, mRNA and
      protein expression of TRP1 was downregulated, and amplitudes of I(SOC) and CCE
      elicited by passive depletion of Ca2+ from the sarcoplasmic reticulum using
      cyclopiazonic acid were significantly reduced in the AS-treated PASMC compared
      with control. Furthermore, the rate of cell growth was decreased by 50% in AS
      treated PASMC. These results indicate that TRP1 may encode a store-operated Ca2+
      channel that plays a critical role in PASMC proliferation by regulating CCE and
      intracellular [Ca2+](cyt).

PMID- 12060572
TI  - Role of macrophage migration inhibitory factor in bleomycin-induced lung injury
      and fibrosis in mice.
AB  - Macrophage migration inhibitory factor (MIF) is a unique cytokine that reportedly
      overrides the anti-inflammatory effect of endogenous glucocorticoids. MIF has
      been demonstrated to be involved in a variety of inflammatory diseases. In this
      study, we examined the role of MIF in bleomycin (BLM)-induced lung injury and
      fibrosis. The levels of MIF in lung tissues and bronchoalveolar lavage fluids
      were significantly increased in the period 5-10 days after intratracheal
      administration of BLM. Treatment with the anti-MIF antibody significantly reduced
      the mortality at 14 days and the histopathological lung injury score at 10 days.
      These effects were accompanied with significant suppression of the accumulation
      of inflammatory cells in the alveolar space and tumor necrosis factor-alpha in
      the lungs at 7 days. However, the anti-MIF antibody did not affect either the
      content of lung hydroxyproline or the histopathological lung fibrosis score at 21
      days after BLM. These data provide further evidence for the crucial role of MIF
      in acute lung inflammation but do not support the involvement of MIF in lung
      fibrosis induced by BLM in mice.

PMID- 12060573
TI  - Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic
      mechanisms.
AB  - Pretreatment with keratinocyte growth factor (KGF) ameliorates experimentally
      induced acute lung injury in rats. Although alveolar epithelial type II cell
      hyperplasia probably contributes, the mechanisms underlying KGF's protective
      effect remain incompletely described. Therefore, we tested the hypothesis that
      KGF given to rats in vivo would enhance alveolar epithelial repair in vitro by
      nonproliferative mechanisms. After intratracheal instillation (48 h) of KGF (5
      mg/kg), alveolar epithelial type II cells were isolated for in vitro alveolar
      epithelial repair studies. KGF-treated cells had markedly increased epithelial
      repair (96 +/- 22%) compared with control cells (P < 0.001). KGF-treated cells
      had increased cell spreading and migration at the wound edge but no increase in
      in vitro proliferation compared with control cells. KGF-treated cells were more
      adherent to extracellular matrix proteins and polystyrene. Inhibition of the
      epidermal growth factor (EGF) receptor with tyrosine kinase inhibitors abolished
      the KGF effect on epithelial repair. In conclusion, in vivo administration of KGF
      augments the epithelial repair rate of alveolar epithelial cells by altering cell
      adherence, spreading, and migration and through stimulation of the EGF receptor.

PMID- 12060574
TI  - Treatment of established asthma in a murine model using CpG
      oligodeoxynucleotides.
AB  - Allergen immunotherapy is an effective but underutilized treatment for atopic
      asthma. We have previously demonstrated that CpG oligodeoxynucleotides (CpG ODN)
      can prevent the development of a murine model of asthma. In the current study, we
      evaluated the role of CpG ODN in the treatment of established eosinophilic airway
      inflammation and bronchial hyperreactivity in a murine model of asthma. In this
      model, mice with established ovalbumin (OVA)-induced airway disease were given a
      course of immunotherapy (using low doses of OVA) in the presence or absence of
      CpG ODN. All mice then were rechallenged with experimental allergen. Untreated
      mice developed marked airway eosinophilia and bronchial hyperresponsiveness,
      which were significantly reduced by treatment with OVA and CpG. CpG ODN leads to
      induction of antigen-induced Th1 cytokine responses; successful therapy was
      associated with induction of the chemokines interferon-gamma-inducible protein-10
      and RANTES and suppression of eotaxin. Unlike previous studies, these data
      demonstrate that the combination of CpG ODN and allergen can effectively reverse
      established atopic eosinophilic airway disease, at least partially through
      redirecting a Th2 to a Th1 response.

PMID- 12060575
TI  - ICAM-1 facilitates alveolar macrophage phagocytic activity through effects on
      migration over the AEC surface.
AB  - We postulate that intercellular adhesion molecule-1 (ICAM-1) on type I alveolar
      epithelial cells (AEC) facilitates phagocytic activity of alveolar macrophages
      (AM) in the alveolus. When wild-type and ICAM-1-deficient mice were inoculated
      intratracheally with FITC-labeled microspheres, AM phagocytosis of beads (after 1
      and 4 h) was significantly reduced in ICAM-1-/- mice compared with controls. To
      focus on ICAM-1-mediated interactions specifically involving AM and AEC, rat AM
      were placed in culture with rat AEC treated with neutralizing anti-ICAM-1
      F(ab')(2) fragments. Blocking ICAM-1 significantly decreased the AM phagocytosis
      of beads. Planar chemotaxis of AM over the surface of AEC was also significantly
      impaired by neutralization of AEC ICAM-1. ICAM-1 in rat AEC is associated with
      the actin cytoskeleton. Planar chemotaxis of AM was also significantly reduced by
      pretreatment of the AEC monolayer with cytochalasin B to disrupt the actin
      cytoskeleton. These studies indicate that ICAM-1 on the AEC surface promotes
      mobility of AM in the alveolus and is critically important for the efficient
      phagocytosis of particulates by AM.

PMID- 12060577
TI  - Eotaxin/CCL11 is involved in acute, but not chronic, allergic airway responses to
      Aspergillus fumigatus.
AB  - Eotaxin/CCL11 is a major chemoattractant for eosinophils and Th2 cells. As such,
      it represents an attractive target in the treatment of allergic disease. The
      present study addresses the role of eotaxin/CCL11 during acute and chronic
      allergic airway responses to the fungus Aspergillus fumigatus. Mice lacking the
      eotaxin gene (Eo-/-) and wild-type mice (Eo+/+) were sensitized to A. fumigatus
      and received either an intratracheal challenge with soluble A. fumigatus antigens
      (acute model) or an intratracheal challenge with live A. fumigatus spores or
      conidia (chronic model). Airway hyperresponsiveness and eosinophil, but not T
      cell, recruitment were significantly decreased at 24 h after the soluble allergen
      in A. fumigatus-sensitized Eo-/- mice compared with similarly sensitized Eo+/+
      mice. In contrast, the development of chronic allergic airway disease due to A.
      fumigatus conidia was not altered by the lack of eotaxin. Together, these data
      suggest that eotaxin initiates allergic airway disease due to A. fumigatus, but
      this chemokine did not appear to contribute to the maintenance of A. fumigatus
      induced allergic airway disease.

PMID- 12060576
TI  - Impairment of macrophage survival by NaCl: implications for early pulmonary
      inflammation in cystic fibrosis.
AB  - Inflammation, characterized by the presence of proinflammatory chemokines and
      neutrophils, is a hallmark of early airway disease in infants with cystic
      fibrosis (CF), although the underlying mechanisms remain poorly defined. In this
      study, we evaluated the role of NaCl and the ensuing hyperosmolar effect on tumor
      necrosis factor (TNF)-alpha signaling and apoptosis in macrophages. Incubation of
      mouse macrophages with NaCl activated p38(mapk) and the p46(jnk) and p54(jnk) c
      jun NH(2)-terminal kinase isoforms, but not p42(mapk/erk2) or Akt. Similar
      results were obtained with sorbitol, suggesting a general response to
      hyperosmolarity. Strikingly, the activation of p42(mapk/erk2) and Akt by TNF
      alpha was also inhibited in the presence of NaCl. Because the activation of
      p42(mapk/erk2) and Akt has been associated with survival responses, we
      investigated the effect of NaCl on macrophage apoptosis. The results indicated a
      synergistic increase in apoptosis when macrophages were exposed to TNF-alpha in
      the presence of NaCl compared with stimulation with TNF-alpha alone or NaCl
      alone. Furthermore, pharmacological inhibition of p42(mapk/erk2) and Akt mimicked
      the effect of NaCl. Collectively, these findings indicate that modest elevations
      in NaCl differentially regulate the activation of mitogen-activated protein
      kinases and Akt and potentiate macrophage apoptosis. We speculate that
      augmentation of macrophage apoptosis in CF airways may result in decreased
      clearance of neutrophils and in deficiencies in the elimination of common CF
      pathogens.

PMID- 12060578
TI  - Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from
      oxidant-mediated death.
AB  - In rat cultured pulmonary arterial (PA), microvascular, and venous endothelial
      cells (ECs), the rate of mitochondrial (mt) DNA repair is predictive of the
      severity of xanthine oxidase (XO)-induced mtDNA damage and the sensitivity to XO
      mediated cell death. To examine the importance of mtDNA damage and repair more
      directly, we determined the impact of mitochondrial overexpression of the DNA
      repair enzyme, Ogg1, on XO-induced mtDNA damage and cell death in PAECs. PAECs
      were transiently transfected with an Ogg1-mitochondrial targeting sequence
      construct. Mitochondria-selective overexpression of the transgene product was
      confirmed microscopically by the observation that immunoreactive Ogg1 colocalized
      with a mitochondria-specific tracer and, with an oligonucleotide cleavage assay,
      by a selective enhancement of mitochondrial Ogg1 activity. Overexpression of Ogg1
      protected against both XO-induced mtDNA damage, determined by quantitative
      Southern analysis, and cell death as assessed by trypan blue exclusion and MTS
      assays. These findings show that mtDNA damage is a direct cause of cell death in
      XO-treated PAECs.

PMID- 12060579
TI  - Overexpression of extracellular superoxide dismutase decreases lung injury after
      exposure to oil fly ash.
AB  - The mechanism of tissue injury after exposure to air pollution particles is not
      known. The biological effect has been postulated to be mediated via an oxidative
      stress catalyzed by metals present in particulate matter (PM). We utilized a
      transgenic (Tg) mouse model that overexpresses extracellular superoxide dismutase
      (EC-SOD) to test the hypothesis that lung injury after exposure to PM results
      from an oxidative stress in the lower respiratory tract. Wild-type (Wt) and Tg
      mice were intratracheally instilled with either saline or 50 microg of residual
      oil fly ash (ROFA). Twenty-four hours later, specimens were obtained and included
      bronchoalveolar lavage (BAL) and lung for both homogenization and light
      histopathology. After ROFA exposure, EC-SOD Tg mice showed a significant
      reduction in BAL total cell counts (composed primarily of neutrophils) and BAL
      total protein compared with Wt. EC-SOD animals also demonstrated diminished
      concentrations of inflammatory mediators in BAL. There was no statistically
      significant difference in BAL lipid peroxidation; however, EC-SOD mice had lower
      concentrations of oxidized glutathione in the BAL. We conclude that enhanced EC
      SOD expression decreased both lung inflammation and damage after exposure to
      ROFA. This supports a participation of oxidative stress in the inflammatory
      injury after PM exposure rather than reflecting a response to metals alone.

PMID- 12060580
TI  - Temporal correlation of measurements of airway hyperresponsiveness in ovalbumin
      sensitized mice.
AB  - Airway hyperresponsiveness, airway inflammation, and reversible airway
      obstruction are physiological hallmarks of asthma. These responses are
      increasingly being studied in murine models of antigen exposure and challenge,
      using whole body plethysmography to noninvasively assess airway
      hyperresponsiveness. This approach infrequently has been correlated with indexes
      of airway hyperresponsiveness measured by invasive means. Furthermore,
      correlation with quantitative histological data for tissue infiltration by
      inflammatory and immune cells, particularly in the wall of airways, during daily
      airway challenge is lacking. To address these uncertainties, we used C57BL/6 mice
      that were immunized with ovalbumin or vehicle (saline) and sensitized to
      aerosolized ovalbumin or vehicle 8 days later. The mice were subsequently exposed
      to aerosolized ovalbumin or vehicle, respectively, on days 14-22. We assessed
      airway hyperresponsiveness to methacholine noninvasively on days 14, 15, 18, or
      22; we studied the same mice 24 h later while they were anesthetized for invasive
      analyses of airway hyperresponsiveness. Plasma total IgE concentration was
      significantly higher in the ovalbumin-treated mice compared with the vehicle
      treated mice, but this did not correlate with eosinophil number. Peak airway
      hyperresponsiveness measured by either approach correlated early during daily
      antigen challenge (days 14 and 15), but this correlation was lost later during
      subsequent daily antigen challenges (days 18 and 22). On days 14 and 15, peak
      airway hyperresponsiveness correlated with transmigration of neutrophils and
      macrophages, but not lymphocytes, in the peribronchovascular connective tissue
      sheaths. This extravascular accumulation was found to be focal by three
      dimensional microscopy. We conclude that, although ovalbumin treatment changed
      lung function in mice, correlation between noninvasive and invasive measures of
      peak airway hyperresponsiveness was inconsistent.

PMID- 12060581
TI  - Relationships between caveolae and eNOS: everything in proximity and the
      proximity of everything.
AB  - Caveolae, flask-shaped invaginations of the plasma membrane occupying up to 30%
      of cell surface in capillaries, represent a predominant location of endothelial
      nitric oxide synthase (eNOS) in endothelial cells. The caveolar coat protein
      caveolin forms high-molecular-weight, Triton-insoluble complexes through
      oligomerization mediated by interactions between NH2-terminal residues 61-101.
      eNOS is targeted to caveolae by cotranslational N-myristoylation and
      posttranslational palmitoylation. Caveolin-1 coimmunoprecipitates with eNOS;
      interaction with eNOS occurs via the caveolin-1 scaffolding domain and appears to
      result in the inhibition of NOS activity. The inhibitory conformation of eNOS is
      reversed by the addition of excess Ca2+/calmodulin and by Akt-induced
      phosphorylation of eNOS. Here, we shall dissect the system using the classic
      paradigm of a reflex loop: 1) the action of afferent elements, such as fluid
      shear stress and its putative caveolar sensor, on caveolae; 2) the ways in which
      afferent signals may affect the central element, the activation of the eNOS
      nitric oxide system; and 3) several resultant well-established and novel
      physiologically important effector mechanisms, i.e., vasorelaxation,
      angiogenesis, membrane fluidity, endothelial permeability, deterrance of
      inflammatory cells, and prevention of platelet aggregation.

PMID- 12060582
TI  - Circulating endothelial cells: tea leaves for renal disease.
AB  - Fully differentiated endothelial cells and their precursors circulate in the
      bloodstream. Since their initial description more than 30 years ago, circulating
      endothelial cells have been quantified in a number of different clinical
      conditions that affect the endothelium. Only recently, however, have
      investigators begun to examine the protein expression and functionality of these
      cells. Because a number of diseases prevalent in the field of nephrology affect
      endothelial cells, the study of circulating endothelial cells may allow the
      direct examination of the state of the endothelium in these conditions. This
      review will discuss the endothelium and renal disease, the methods to quantify
      these circulating endothelial cells, their origins, and their therapeutic
      potential.

PMID- 12060583
TI  - Extracellular glutathione peroxidase is secreted basolaterally by human renal
      proximal tubule cells.
AB  - Extracellular glutathione peroxidase (eGPx) is a secreted selenoenzyme with GPx
      activity. eGPx protein and activity are found in blood plasma and other
      extracellular fluids. eGPx in plasma is predominantly derived from the proximal
      tubules of kidneys in humans. Two types of human proximal tubule cells were
      cultured on semipermeable polycarbonate membranes to determine whether these
      cells secrete eGPx in a polarized direction. Immortalized human proximal tubule
      HK-2 cells and primary human proximal tubule cells formed confluent monolayers
      when cultured on these membrane inserts in culture dishes, as evidenced by
      transepithelial resistance. Both cell lines also constituted a barrier to
      diffusion of a fluoresceinated dextran of 75 kDa, a size similar to eGPx
      homotetramers. In both cell lines, 6- to 12-fold more 35S-methionine-labeled eGPx
      was immunoprecipitated from the basolateral media than from the apical media,
      indicating basolateral secretion of eGPx. eGPx was immunolocalized to the
      extracellular fluid at the basolateral surface of proximal tubules in human
      kidney. These data support the conclusion that eGPx is secreted through the
      basolateral membrane of human kidney proximal tubule cells into the extracellular
      fluid of the kidney, and from there enters blood plasma.

PMID- 12060584
TI  - Plasma membrane Ca2+-ATPase and NCX1 Na+/Ca2+ exchanger expression in distal
      convoluted tubule cells.
AB  - The plasma membrane Ca2+-ATPase (PMCA) and the NCX1 Na+/Ca2+ exchanger regulate
      intracellular Ca2+ concentrations and mediate Ca2+ efflux in absorptive
      epithelial cells. We characterized the PMCA isoforms and subtypes expressed in
      mouse distal convoluted tubule (mDCT) cells and Na+/Ca2+ exchanger protein
      expression in mDCT cells. In lysates of mDCT cells, immunoprecipitation and
      Western blot analysis, performed with a monoclonal antibody to PMCA, revealed a
      140-kDa protein consistent with PMCA. Laser-scanning confocal fluorescence
      microscopy indicated that PMCA and NCX1 expression is restricted to basolateral
      membranes only in confluent mDCT cells, because subconfluent cultures
      predominately express intracellular localizations. PMCA isoform-specific PCR
      primers generated appropriately sized products only for PMCA1 and PMCA4 from DCT
      cells but PMCA1-4 from whole mouse kidney. Assessment of splice site C within the
      calmodulin-binding domain demonstrated the presence of PMCA1b and PMCA4b mRNAs in
      mDCT cells. Northern blot analysis of mDCT cell RNA revealed transcripts of 7.5
      and 5.5 kb for PMCA1 and 8.5 and 7.5 kb for PMCA4. We conclude that DCT cells
      express PMCA transcripts encoding PMCA1b and PMCA4b. Basolateral localization of
      the Na+/Ca2+ exchanger and MCAs support the idea that multiple PMCA isoforms, in
      concert with the Na+/Ca2+ exchanger, mediate basal or hormone-stimulated Ca2+
      efflux by distal tubules.

PMID- 12060585
TI  - Expression of adenosine receptors in the preglomerular microcirculation.
AB  - The purpose of this study was to systematically investigate the abundance of each
      of the adenosine receptor subtypes in the preglomerular microcirculation vs.
      other vascular segments and vs. the renal cortex and medulla. Rat preglomerular
      microvessels (PGMVs) were isolated by iron oxide loading followed by magnetic
      separation. For comparison, mesenteric microvessels, segments of the aorta
      (thoracic, middle abdominal, and lower abdominal), renal cortex, and renal
      medulla were obtained by dissection. Adenosine receptor protein and mRNA
      expression were examined by Western blotting, Northern blotting, and RT-PCR. Our
      results indicate that compared with other vascular segments and renal tissues, A1
      and A2B receptor protein and mRNA are abundantly expressed in the preglomerular
      microcirculation, whereas A2A and A3 receptor protein and mRNA are barely
      detectable or undetectable in PGMVs. We conclude that, relative to other vascular
      and renal tissues, A1 and A2B receptors are well expressed in PGMVs, whereas A2A
      and A3 receptors are notably deficient. Thus A1 and A2B receptors, but not A2A or
      A3 receptors, may importantly regulate the preglomerular microcirculation.

PMID- 12060586
TI  - Alterations in renal mitochondrial respiration in response to the reactive
      oxoaldehyde methylglyoxal.
AB  - Chronic hyperglycemia has been linked to alterations in mitochondrial function,
      suggesting an important role in the pathophysiology of the complications of
      diabetes mellitus. In the diabetic kidney, ultrastructural changes in
      mitochondria are associated with impaired tubular function. The goal of this
      study was to determine if methylglyoxal (MGO), a dicarbonyl compound reaching
      high levels in hyperglycemic conditions, has direct toxicity for renal
      mitochondria. Intact mitochondria isolated from the renal cortex of rats were
      incubated with MGO to determine 1) its effect on mitochondrial respiration, 2)
      the conditions under which MGO exerts these effects, and 3) the potential
      mitochondrial targets of MGO influence. This study demonstrates that MGO has an
      inhibitory effect on both the tricarboxylic acid cycle and the electron
      respiratory chain. The modifications appear to be specific to certain
      mitochondrial proteins. Alterations of these proteins lead to disturbances in
      mitochondria that may play an important role in renal cellular toxicity and in
      the development of diabetic nephropathy.

PMID- 12060587
TI  - Cytochrome P-450 4A isoform expression and 20-HETE synthesis in renal
      preglomerular arteries.
AB  - 20-Hydroxyeicosatetraenoic acid (20-HETE), a potent vasoconstrictor and mediator
      of the myogenic response, is a major arachidonic acid metabolite in the
      microvasculature of the rat kidney formed primarily by the cytochrome P-450 (CYP)
      4A isoforms, CYP4A1, CYP4A2, and CYP4A3. We examined CYP4A isoform expression and
      20-HETE synthesis in microdissected interlobar, arcuate, and interlobular
      arteries; mRNA for all CYP4A isoforms was identified by RT-PCR. Western blot
      analysis indicated that the levels of CYP4A2/4A3-immunoreactive protein increased
      with decreased arterial diameter, whereas those of CYP4A1-immunoreactive protein
      remained unchanged. 20-HETE synthesis was the highest in the interlobular
      arteries (17 +/- 1.62 nmol. mg(-1). h(-1)) and, like CYP4A2/4A3-immunoreactive
      protein, decreased with increasing vessel diameter (4.5 +/- 1.21, 2.65 +/- 0.58,
      and 0.81 +/- 0.14 nmol. mg(-1). h(-1) in the arcuate, interlobar, and segmental
      arteries, respectively). 20-HETE synthesis in the renal artery and the abdominal
      aorta was undetectable. The observed decreased immunoreactivity of NADPH
      cytochrome P-450 (c) oxidoreductase with increased arterial diameter provided a
      possible explanation for the decreased capacity to generate 20-HETE in the large
      arteries. The increase in CYP4A isoform expression and 20-HETE synthesis with
      decreasing diameter along the preglomerular arteries and the potent biological
      activity of 20-HETE underscore the significance of 20-HETE as a modulator of
      renal hemodynamics.

PMID- 12060588
TI  - Cyclooxygenase-2 products compensate for inhibition of nitric oxide regulation of
      renal perfusion.
AB  - Cyclooxygenase (COX)-2 is in the macula densa, cosegregating with neuronal nitric
      oxide synthase (nNOS). It is hypothesized that in response to acute inhibition of
      NOS, the influence of COX-2-derived prostanoids is exaggerated, compensating for
      renal vasoconstriction. Blood pressure (BP) and renal blood flow (RBF) were
      measured after selective COX-2 inhibition with NS-398 followed by NOS inhibition
      with L-nitro arginine methyl ester (L-NAME) or after L-NAME followed by NS-398.
      BP was 106 +/- 4 mmHg and was unaffected by NS-398. L-NAME after NS-398 increased
      BP by 27 +/- 2 mmHg, decreased RBF by one-half, and doubled renal vascular
      resistance (RVR; P < 0.001). Initial L-NAME increased BP by 26 +/- 3 mmHg (P <
      0.001) and decreased RBF by 44% (P < 0.001), doubling RVR. After L-NAME, NS-398
      induced a further 7 +/- 3-mmHg rise in BP (P < 0.05), decreased RBF by 20% (P <
      0.025), and increased RVR by 23% (P < 0.01). The constrictor response to COX-2
      inhibition after L-NAME could not be duplicated by either selective nNOS
      inhibition or NOS-independent renal vasoconstriction. Acute NOS inhibition
      unmasked renal vasoconstriction with COX-2 inhibition, suggesting that the
      influence of COX-2-derived vasodilator eicosanoids is exaggerated to maintain
      renal perfusion, compensating for the acute loss of NO.

PMID- 12060589
TI  - Expression and function of sodium transporters in two opossum kidney cell clonal
      sublines.
AB  - The present study describes characteristic features of two clonal subpopulations
      of opossum kidney (OK) cells (OK(LC) and OK(HC)) that are functionally different
      but morphologically identical. The most impressive differences between OK(HC) and
      OK(LC) cells are the overexpression of Na+-K+-ATPase and type 3 Na+/H+ exchanger
      by the former, accompanied by an increased Na+-K+-ATPase activity (57.6 +/- 5.6
      vs. 30.0 +/- 0.1 nmol P(i). mg protein(-1). min(-1)); the increased ability to
      translocate Na+ from the apical to the basolateral surface; and the increased Na+
      dependent pH(i) recovery (0.254 +/- 0.016 vs. 0.094 +/- 0.011 pH units/s). Vmax
      values (in pH units/s) for Na+-dependent pHi recovery in OK(HC) cells (0.00521 +/
      0.0004) were twice (P < 0.05) those in OK(LC) (0.00202 +/- 0.0001), with similar
      Km values (in mM) for Na+ (OK(LC), 21.0 +/- 5.5; OK(HC), 14.0 +/- 5.6). In
      addition, we measured the activities of transporters (organic ions, alpha-methyl
      D-glucoside, L-type amino acids, and Na+ and enzymes (adenylyl cyclase, aromatic
      L-amino acid decarboxylase, and catechol-O-methyltransferase). The cells were
      also characterized morphologically by optical and scanning electron microscopy
      and karyotyped. It is suggested that OK(LC) and OK(HC) cells constitute an
      interesting cell model for the study of renal epithelial physiology and
      pathophysiology, namely, hypertension.

PMID- 12060590
TI  - Renal microvascular actions of angiotensin II fragments.
AB  - In the present study, we investigated renal microvascular responses to ANG-(1-7)
      and ANG IV. Diameter changes of small interlobular arteries, afferent arterioles,
      and efferent arterioles were assessed by using isolated perfused hydronephrotic
      rat kidneys. ANG-(1-7) and ANG IV concentration dependently decreased the
      diameters of all investigated renal microvessel, however, with a much lower
      potency than ANG II. The ANG II type 1 receptor blocker irbesartan completely
      reversed the responses to ANG-(1-7) and ANG IV, whereas the ANG II type 2
      receptor blocker PD-123319 had no effect. Both ANG-(1-7) and ANG IV failed to
      alter renal microvascular constriction induced by ANG II. In addition,
      subnanomolar concentrations of ANG-(1-7) had no effect on the myogenic-induced
      tone of interlobular arteries and afferent arterioles. Thus our data indicate
      that at high concentrations, ANG-(1-7) and ANG IV are able to activate the ANG II
      type 1 receptor, thereby inducing renal microvascular constriction. The failure
      of ANG-(1-7) and ANG IV to reduce ANG II- and pressure-induced constrictions
      suggests that these fragments do not exert a vasodilator and/or ANG II
      antagonistic action in the kidney.

PMID- 12060591
TI  - A mechanogated nonselective cation channel in proximal tubule that is ATP
      sensitive.
AB  - Ion channels that are gated in response to membrane deformation or "stretch" are
      empirically designated stretch-activated channels. Here we describe a stretch
      activated nonselective cation channel in the basolateral membrane (BLM) of the
      proximal tubule (PT) that is nucleotide sensitive. Single channels were studied
      in cell-intact and cell-free patches from the BLM of PT cells that maintain their
      epithelial polarity. The limiting inward Cs+ conductance is ~28 pS, and channel
      activity persists after excision into a Ca2+- and ATP-free bath. The stretch-dose
      response is sigmoidal, with half-maximal activation of about -19 mmHg at -40 mV,
      and the channel is activated by depolarization. The inward conductance sequence
      is: NH ~ Cs+ ~ Rb+ > K+ ~ Na+ ~ Li+ > Ca2+ ~ Ba2+ > N-methyl-D-glucamine ~
      tetraethylammonium. The venom of the common Chilean tarantula, Grammostola
      spatulata, completely blocks channel activity in cell-attached patches. Hypotonic
      swelling reversibly activates the channel. Intracellular ATP concentration
      ([ATP]i) reversibly blocks the channel (inhibitory constant approximately 0.48
      mM), suggesting that channel function is coupled to the metabolic state of the
      cell. We conclude that this channel may function as a Ca2+ entry pathway and/or
      be involved in regulation of cell volume. We speculate this channel may be
      important when [ATP]i is depleted, as occurs during periods of increased
      transepithelial transport or with ischemic injury.

PMID- 12060592
TI  - Hypotonic induction of SGK1 and Na+ transport in A6 cells.
AB  - Serum and glucocorticoid-regulated kinase-1 (SGK1) is a serine-threonine kinase
      that is regulated at the transcriptional level by numerous regulatory inputs,
      including mineralocorticoids, glucocorticoids, follicle-stimulating hormone, and
      osmotic stress. In the distal nephron, SGK1 is induced by aldosterone and
      regulates epithelial Na+ channel-mediated transepithelial Na+ transport. In other
      tissues, including liver and shark rectal gland, SGK1 is regulated by hypertonic
      stress and is thought to modulate epithelial Na+ channel- and Na+-K+-2Cl-
      cotransporter-mediated Na+ transport. In this report, we examined the regulation
      of SGK1 mRNA and protein expression and Na+ currents in response to osmotic
      stress in A6 cells, a cultured cell line derived from Xenopus laevis distal
      nephron. We found that in contrast to hepatocytes and rectal gland cells,
      hypotonic conditions stimulated SGK1 expression and Na+ transport in A6 cells.
      Moreover, a correlation was found between SGK1 induction and the later phase of
      activation of Na+ transport in response to hypotonic treatment. When A6 cells
      were pretreated with an inhibitor of phosphatidylinositol 3-kinase (PI3K), Na+
      transport was blunted and only inactive forms of SGK1 were expressed.
      Surprisingly, these results demonstrate that both hypertonic and hypotonic
      stimuli can induce SGK1 gene expression in a cell type-dependent fashion.
      Moreover, these data lend support to the view that SGK1 contributes to the
      defense of extracellular fluid volume and tonicity in amphibia by mediating a
      component of the hypotonic induction of distal nephron Na+ transport.

PMID- 12060593
TI  - D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on
      the opening of K+ channels.
AB  - This study examined the effects of D2-like dopamine receptor activation on Na+-K+
      ATPase activity while apical-to-basal, ouabain-sensitive, amphotericin B-induced
      increases in short-circuit current and basolateral K+ (I(K)) currents in opossum
      kidney cells were measured. The inhibitory effect of dopamin on Na+-K+-ATPase
      activity was completely abolished by either D1- or D2-like receptor antagonists
      and mimicked by D1- and D2-like receptor agonists SKF-38393 and quinerolane,
      respectively. Blockade of basolateral K+ channels with BaCl2 (1 mM) or
      glibenclamide (10 microM), but not apamin (1 microM), totally prevented the
      inhibitory effects of quinerolane. The K+ channel opener pinacidil decreased Na+
      K+-ATPase activity. The inhibitory effect of quinerolane on Na+-K+- ATPase
      activity was abolished by pretreatment of opossum kidney cells with pertussis
      toxin (PTX). Quinerolane increased I(K) across the basolateral membrane in a
      concentration-dependent manner; this effect was abolished by pretreatment with
      PTX, S-sulpiride, and glibenclamide. SKF-38393 did not change I(K). Both H-89
      (protein kinase A inhibitor) and chelerythrine (protein kinase C inhibitor)
      failed to prevent the stimulatory effect of quinerolane on I(K). The stimulation
      of the D2-like receptor was associated with a rapid hyperpolarizing effect,
      whereas D1-like receptor activation was accompanied by increases in cell membrane
      potential. It is concluded that stimulation of D2-like receptors leads to
      inhibition of Na+-K+-ATPase activity and hyperpolarization; both effects are
      associated with the opening of K+ channels.

PMID- 12060594
TI  - Molecular cloning of rabbit organic cation transporter rbOCT2 and functional
      comparisons with rbOCT1.
AB  - Multiple organic cation transporters (OCTs) are present in rabbit kidney and may
      play different functional roles. We cloned rabbit OCT2 (rbOCT2) and compared its
      function with that of rabbit OCT1 (rbOCT1). In transiently transfected COS-7
      cells, rbOCT1 and rbOCT2 mediated uptake of [3H]tetraethylammonium (TEA) with
      K(t) values of 188 and 125 microM, respectively. n-Tetraalkylammonium compounds
      showed similar affinities for the two homologs, with IC50 values for inhibition
      of OCT1- and OCT2-mediated [3H]TEA transport, respectively, of 4,538 and 1,395
      microM for tetramethylammonium, 88.5 and 3.9 microM for tetrapropylammonium, 13.9
      and 5.3 microM for tetrabutylammonium, and 8.8 and 7.6 microM for
      tetrapentylammonium. However, the transporters had very different affinities for
      cimetidine (CIM): IC50 of 916 and 5.7 microM for rbOCT1 and rbOCT2, respectively.
      CIM inhibition of TEA uptake into single S2 segments of rabbit proximal tubule
      was used to estimate the contributions of OCT1 and OCT2 to basolateral organic
      cation uptake. The median IC50 for CIM inhibition of TEA uptake was 12.3 microM,
      suggesting that OCT2 is the major contributor to basolateral organic cation
      transport in the S2 segment of proximal tubule in rabbit kidney.

PMID- 12060595
TI  - Reduced osmotically inactive Na storage capacity and hypertension in the Dahl
      model.
AB  - Recent evidence suggested that Na can be stored in an osmotically inactive form.
      We investigated whether osmotically inactive Na storage is reduced in a rat model
      of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as
      well as Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.1%)-NaCl diet
      for 4 wk (n = 10/group). Mean arterial pressure (MAP) was measured at the end of
      the experiment. Wet and dry weights, water content, total body Na (TBS), and bone
      Na content were measured by dessication and dry ashing. MAP was higher in both
      Dahl strains than in SD rats. In SS rats, 8% NaCl led to Na accumulation, water
      retention, and hypertension due to impaired renal Na excretion. There was no
      dietary-induced Na retention in SR and SD rats. TBS was variable; nevertheless,
      TBS was significantly correlated with body water and MAP in all strains. However,
      the extent of Na-associated volume and MAP increases was strain specific.
      Osmotically inactive Na in SD rats was threefold higher than in SS and SR rats.
      Both SS and SR Dahl rat strains displayed reduced osmotically inactive Na storage
      capacity compared with SD controls. A predisposition to fluid accumulation and
      high blood pressure results from this alteration. Additional factors, including
      impaired renal Na excretion, probably contribute to hypertension in SS rats. Our
      results draw attention to the role of osmotically inactive Na storage.

PMID- 12060596
TI  - Regulation of the voltage-gated K+ channel KCNA10 by KCNA4B, a novel beta
      subunit.
AB  - Voltage-gated K+ (Kv) channels are heteromultimeric complexes consisting of pore
      forming alpha-subunits and accessory beta-subunits. Several beta-subunits have
      been identified and shown to interact with specific alpha-subunits to modify
      their levels of expression or some of their kinetic properties. The aim of the
      present study was to isolate accessory proteins for KCNA10, a novel Kv channel
      alpha-subunit functionally related to Kv and cyclic nucleotide-gated cation
      channels. Because one distinguishing feature of KCNA10 is a putative cyclic
      nucleotide-binding domain located at the COOH terminus, the entire COOH-terminal
      region was used to probe a human cardiac cDNA library using the yeast two-hybrid
      system. Interacting clones were then rescreened in a functional assay by
      coinjection with KCNA10 in Xenopus oocytes. One of these clones (KCNA4B), when
      injected alone in oocytes, produced no detectable current. However, when
      coinjected with KCNA10, it increased KCNA10 current expression by nearly
      threefold. In addition, the current became more sensitive to activation by cAMP.
      KCNA4B can be coimmunoprecipitated with the COOH terminus of KCNA10 and full
      length KCNA10. It encodes a soluble protein (141 aa) with no amino acid homology
      to known beta-subunits but with limited structural similarity to the NAD(P)H
      dependent oxidoreductase superfamily. KCNA4B is located on chromosome 13 and
      spans approximately16 kb, and its coding region is made up of five exons. In
      conclusion, KCNA4B represents the first member of a new class of accessory
      proteins that modify the properties of Kv channels.

PMID- 12060597
TI  - Functional analysis and molecular model of the human urate transporter/channel,
      hUAT.
AB  - Recombinant protein, designated hUAT, the human homologue of the rat urate
      transporter/channel (UAT), functions as a highly selective urate channel in lipid
      bilayers. Functional analysis indicates that hUAT activity, like UAT, is
      selectively blocked by oxonate from its cytosolic side, whereas pyrazinoate and
      adenosine selectively block from the channel's extracellular face. Importantly,
      hUAT is a galectin, a protein with two beta-galactoside binding domains that bind
      lactose. Lactose significantly increased hUAT open probability but only when
      added to the channel's extracellular side. This effect on open probability was
      mimicked by glucose, but not ribose, suggesting a role for extracellular glucose
      in regulating hUAT channel activity. These functional observations support a four
      transmembrane-domain structural model of hUAT, as previously predicted from the
      primary structure of UAT. hUAT and UAT, however, are not functionally identical:
      hUAT has a significantly lower single-channel conductance and open probability is
      voltage independent. These differences suggest that evolutionary changes in
      specific amino acids in these highly homologous proteins are functionally
      relevant in defining these biophysical properties.

PMID- 12060598
TI  - Temporal decrease in renal sensory responses in rats after chronic ligation of
      the bile duct.
AB  - Renal responses to renal sensory receptor activation were examined in rats after
      1 and 4 wk of common bile duct ligation (CBDL). Compared with sham-operated rats
      (Sham), urine and sodium excretion after acute saline loading was significantly
      reduced at both times after CBDL. The blunted excretory responses in CBDL rats,
      accompanied by less activation of afferent renal nerve activity (ARNA), were
      already apparent at 1 wk and became severe at 4 wk. The defect in ARNA activation
      in CBDL rats was further studied using specific stimuli to activate renal sensory
      receptors. Graded increases in intrapelvic pressure or renal pelvic perfusion of
      substance P (SP) elicited an increase in ARNA in Sham rats, these responses being
      temporally attenuated in CBDL rats. Despite no significant change in renal pelvic
      SP release, no renorenal reflex was demonstrable in 4-wk CBDL rats.
      Immunoblotting showed that expression of renal pelvic neurokinin 1 (NK-1)
      receptors was 32 and 47% lower in 1- and 4-wk CBDL rats, respectively, than in
      Sham rats, this decrease correlating well with plasma SP levels. The quantitative
      real-time RT-PCR showed similar levels of NK-1 receptor mRNA in the renal pelvis
      in the Sham and 4-wk CBDL groups. We conclude that impairment of renal excretory
      and sensory responses increases with the duration of cirrhosis. An impaired
      renorenal reflex in cirrhotic rats is involved in the defective activation of the
      renal sensory receptors could be due, in part, to the low expression of NK-1
      receptors, which is dependent on the duration of CBDL. The decrease in NK-1
      receptor protein levels is not due to a decrease in mRNA levels.

PMID- 12060599
TI  - Angiotensin II induces apoptosis in rat glomerular epithelial cells.
AB  - ANG II has been shown to modulate kidney cell growth and contribute to the
      pathobiology of glomerulosclerosis. Glomerular visceral epithelial cell (GEC)
      injury or loss is considered to play a pivotal role in the initiation and
      progression of glomerulosclerosis. In the present study, we investigated the
      effect of ANG II on GEC apoptosis. Rat GECs were incubated with increasing doses
      of ANG II for variable time periods. Apoptosis was evaluated by cell nucleus
      staining and DNA fragmentation assay. ANG II induced GEC apoptosis in a dose- and
      time-dependent manner. The proapoptotic effect was attenuated by the ANG II
      receptor type 1 antagonist losartan or the ANG II receptor type 2 antagonist PD
      123319 and was completely blocked by incubation with the combined antagonists.
      Moreover, ANG II stimulated transforming growth factor (TGF)-beta1 production as
      measured by ELISA. GECs exposed to TGF-beta1 demonstrated a dose- and time
      dependent increase in apoptosis. ANG II-induced apoptosis was significantly
      inhibited by addition of anti-TGF-beta1 antibody. ANG II also upregulated the
      expression of Fas, FasL, and Bax and downregulated the expression of Bcl-2 in
      GECs. These studies suggest that ANG II induces GEC apoptosis by a mechanism
      involving TGF-beta1 expression that may, importantly, contribute to the
      pathogenesis of glomerulosclerosis.

PMID- 12060600
TI  - Apical heterodimeric cystine and cationic amino acid transporter expressed in
      MDCK cells.
AB  - The luminal uptake of L-cystine and cationic amino acids by (re)absorptive
      epithelia, as found in the small intestine and the proximal kidney tubule, is
      mediated by the transport system b(0,+), which is defective in cystinuria.
      Expression studies in Xenopus laevis oocytes and other nonepithelial cells as
      well as genetic studies on cystinuria patients have demonstrated that two gene
      products, the glycoprotein rBAT and the multitransmembrane-domain protein
      b(0,+)AT, are required for system b(0,+) function. To study the biosynthesis,
      surface expression, polarity, and function of this heterodimer in an epithelial
      context, we established stable Madin-Darby canine kidney (MDCK) cell lines
      expressing rBAT and/or b(0,+)AT. Confocal immunofluorescence microscopy shows
      that both subunits depend on each other for apical surface expression.
      Immunoprecipitation of biosynthetically labeled proteins indicates that b(0,+)AT
      is stable in the absence of rBAT, whereas rBAT is rapidly degraded in the absence
      of b(0,+)AT. When both are coexpressed, they associate covalently and rBAT
      becomes fully glycosylated and more stable. Functional experiments show that the
      expressed transport is of the high-affinity b(0,+)-type and is restricted to the
      apical side of the epithelia. In conclusion, coexpression experiments in MDCK
      cell epithelia strongly suggest that the intracellular association of rBAT and
      b(0,+)AT is required for the surface expression of either subunit, which together
      form a functional heterocomplex at the apical cell membrane.

PMID- 12060601
TI  - Effects of microinjection of synthetic Bcl-2 domain peptides on apoptosis of
      renal tubular epithelial cells.
AB  - Bcl-2 protein family members are among the key regulators of the apoptosis
      effector phase. Therefore, we investigated the ability of synthetic peptides
      derived from proteins of the Bcl-2 family, namely, the NH2-terminal region of Bcl
      2 (Bcl2_syn), a central domain of Bax (Bax_syn), and a central domain of Bak
      (Bak_syn) to interfere with the apoptotic process in LLC-PK1 cells. Apoptosis was
      induced by tacrolimus or lipopolysaccharide treatment, and microinjection of
      Bcl2_syn into stimulated LLC-PK1 cells significantly reduced the percentage of
      apoptotic cells detected within 4 h after the treatment. Microinjection of
      Bax_syn or Bax_syn, in contrast, induced apoptosis in otherwise untreated LLC-PK1
      cells during the same period of time. A random sequence control peptide
      (Control_syn), which served as a negative control, as well as FITC-labeled
      dextran, which was coinjected in all experiments for visualization, were
      ineffective in either preventing or inducing apoptosis. These results suggest
      that synthetic peptides mimicking the functional domains of proteins of the Bcl-2
      family are capable of regulating apoptosis when microinjected into LLC-PK1 cells
      in vivo. Analogs to these regulatory peptides could therefore provide valuable
      lead compounds in the therapeutical context.

PMID- 12060602
TI  - Two-photon excitation fluorescence imaging of the living juxtaglomerular
      apparatus.
AB  - Recently, multiphoton excitation fluorescence microscopy has been developed that
      offers important advantages over confocal imaging, particularly for in vivo
      visualization of thick tissue samples. We used this state-of-the-art technique to
      capture high-quality images and study the function of otherwise inaccessible cell
      types and complex cell structures of the juxtaglomerular apparatus (JGA) in
      living preparations of the kidney. This structure has multiple cell types that
      exhibit a complex array of functions, which regulate the process of filtrate
      formation and renal hemodynamics. We report, for the first time, on high
      resolution three-dimensional morphology and Z-sectioning through isolated,
      perfused kidney glomeruli, tubules, and JGA. Time-series images show how
      alterations in tubular fluid composition cause striking changes in single-cell
      volume of the unique macula densa tubular epithelium in situ and how they also
      affect glomerular filtration through alterations in associated structures within
      the JGA. In addition, calcium imaging of the glomerulus and JGA demonstrates the
      utility of this system in capturing the complexity of events and effects that are
      exerted by the specific hypertensive autacoid angiotensin II. This imaging
      approach to the study of isolated, perfused live tissue with multiphoton
      microscopy may be applied to other biological systems in which multiple cell
      types form a functionally integrated syncytium.

PMID- 12060603
TI  - Upregulation of renal BSC1 and TSC in prenatally programmed hypertension.
AB  - Prenatal factors, especially intrauterine growth retardation, have been shown to
      correlate with the risk of essential hypertension in adult life, but the
      mechanisms are unknown. An experimental model of prenatal programming of
      hypertension in the rat, induced by a maternal low-protein diet during pregnancy,
      was employed to study the role of renal Na reabsorption in the pathogenesis. The
      abundance of the apical Na transporter type III Na/H exchanger (NHE3), bumetanide
      sensitive Na-K-2Cl cotransporter (BSC1), thiazide-sensitive Na-Cl cotransporter
      (TSC), and the amiloride-sensitive epithelial Na channel (ENaC) was determined by
      semiquantitative immunoblotting in kidneys from the offspring at 4 wk of age,
      before hypertension became manifest. There were no significant differences
      between the experimental and control rats in the abundance of NHE3 or any of the
      ENaC subunits. In contrast, the quantity of BSC1 in the experimental group was
      increased to 302% of control (P < 0.001) and that of TSC to 157% of control (P <
      0.05). Determination of specific mRNA levels by ELISA-linked RT-PCR revealed a
      significantly increased BSC1 mRNA at 1 day (P < 0.01), 4 wk (P < 0.01), and 8 wk
      (P < 0.001) of age, and a significantly increased TSC mRNA at 4 wk of age (P <
      0.05) in the experimental group. The results suggest that prenatal programming of
      hypertension involves transcriptional upregulation of Na transport in thick
      ascending limb and distal convoluted tubule.

PMID- 12060604
TI  - Mechanisms of glucocorticoid-mediated apoptosis in hematological malignancies.
AB  - Although glucocorticoids (GCs) have been used for their immunosuppressive, anti
      inflammatory, and cytotoxic effects for many years, their precise mechanism of
      action has not been fully elucidated. Evidence indicates that GCs induce
      apoptosis in hematological cells, thus supporting their use as chemotherapeutic
      agents for leukemias, lymphomas, and myeloma. Although much research has been
      focused on investigating the mechanism of action responsible for GC-mediated cell
      death, the signaling pathways remain unclear. Two schools of thought have
      developed to account for GC-induced apoptosis. One supports the hypothesis that
      apoptosis is achieved via activation of death-inducing genes. The second theory
      states that GCs induce apoptosis via repression of transcription factor activity,
      thereby inhibiting the transcription of growth/survival genes. This review will
      attempt to clarify the complex signaling pathway responsible for mediating GC
      induced apoptosis of hematological cells and to summarize the most current
      research in this field.

PMID- 12060605
TI  - The expanding role of PTEN in neoplasia: a molecule for all seasons? Commentary
      re: M. A. Davies, et al., Adenoviral-mediated expression of MMAC/PTEN inhibits
      proliferation and metastasis of human prostate cancer cells. Clin. Cancer Res.,
      8: 1904-1914, 2002.
AB  - Not since the discovery of p53 has another molecule received as much attention as
      PTEN. In the 5 years since the discovery of PTEN, encoding a dual specificity
      phosphatase tumor suppressor on 10q23, it has been shown to be a susceptibility
      gene for an inherited cancer syndrome, Cowden syndrome, and for several
      developmental disorders; it has been shown to play a prominent role in normal
      murine and human development; and it has been shown to be instrumental in cell
      cycle arrest, apoptosis, and/or possibly cell migration and cytoskeletal affairs.
      Initial work on cancer cell lines had suggested that PTEN caused every type of
      cancer because it was reported that a relatively high frequency of a variety of
      cancer cell lines, whether derived from solid tumors or hematological
      malignancies, had homozygous or compound heterozygous genetic alterations
      involving PTEN. Such data, together with the germ-line human and murine model
      data, suggested that PTEN mutations occurred "early" in sporadic tumorigenesis.
      However, subsequent painstaking work in noncultured primary tumors and in careful
      in vitro overexpression studies over the last 4 years demonstrated that the
      mechanism of PTEN inactivation can be varied and might be cell type dependent.
      Furthermore, apart from sporadic endometrial carcinoma, PTEN alteration in
      noncultured sporadic neoplasias likely occurs "late," promoting progression and
      metastasis. The article by Davies et al. (Clin Cancer Res., 8: 1904-1914, 2002)
      sheds light on all of these issues when they report on data that derive from a
      "triple threat" strategy, i.e., in vitro, in vivo, and ex vivo, to demonstrate
      that adenoviral infection of PTEN into PTEN-null PC3 prostate cancer cell lines
      results in decreased metastatic potential without significantly altering tumor
      size via the predominant mechanism of G(1) cell cycle arrest but not apoptosis.

PMID- 12060606
TI  - New HER2-directed therapies for breast cancer. Commentary re: C. I. Spiridon et
      al., Targeting multiple Her-2 epitopes with monoclonal antibodies results in
      improved antigrowth activity. Clin. Cancer Res., 8: 1720-1730, 2002.

PMID- 12060607
TI  - Targeted delivery in primary and metastatic brain tumors: summary report of the
      seventh annual meeting of the Blood-Brain Barrier Disruption Consortium.
AB  - The November 2000 NIH report of the Brain Tumor Progress Review Group identified
      delivering and targeting therapeutic agents as a priority in the treatment of
      malignant brain tumors. For this reason, the seventh annual Blood-Brain Barrier
      Disruption Consortium meeting, partially funded by an NIH R13 Grant, focused on
      recent advances in targeted delivery to the central nervous system, clinical
      trials for primary and metastatic brain tumors using enhanced chemotherapy
      delivery, and strategies to lessen the toxicities associated with dose intensive
      treatments, using thiols.

PMID- 12060608
TI  - A new human antitumor immunoreagent specific for ErbB2.
AB  - PURPOSE: Our aim was to isolate a novel human mini-antibody(scFv) that
      specifically targets ErbB2-positive cancer cells. ErbB2, a tyrosinekinase
      receptor, is overexpressed in clinically significant tumors, such as breast,
      ovary, and lung carcinomas. In normal tissues, it is expressed only in certain
      epithelial cell types. EXPERIMENTAL DESIGN: A large phagemid library (Griffin.1
      library) of human scFv was used for the isolation of the ErbB2-specific scFv. A
      very effective strategy was developed for the isolation, consisting in a double
      subtractive selection, the use of two different combinations of "positive," i.e.,
      ErbB2-bearing, and "negative" cell lines. RESULTS: Here we report the isolation
      of the first human anti-ErbB2 mini-antibody endowed with antitumor action. Both
      in its soluble and phage format, it binds specifically to ErbB2, inhibits its
      autophosphorylation, is internalized by target cells, and exerts a strong and
      specific antiproliferative action on ErbB2-positive target cells. A correlation
      was found between the extent of this antiproliferative effect and the expression
      levels of ErbB2 on target cells, with a strong cytotoxicity for hyper-expressing
      cells, such as SKBR3, in which apoptosis was evidenced. CONCLUSIONS: This scFv is
      a potentially effective immunoreagent for diagnostics and therapeutics of certain
      cancers, both as a readily diffused molecule in solid tumors and as an essential
      asset for the construction of fully human anticancer drugs.

PMID- 12060609
TI  - Targeting multiple Her-2 epitopes with monoclonal antibodies results in improved
      antigrowth activity of a human breast cancer cell line in vitro and in vivo.
AB  - Her-2 (p185(erbB-2)) is a transmembrane tyrosine kinase receptor, which is
      encoded by the Her-2/neu proto-oncogene. Her-2 is overexpressed on 30% of highly
      malignant breast cancers. Monoclonal antibodies (MAbs) against Her-2 inhibit the
      growth of Her-2-overexpressing tumor cells and this occurs by a variety of
      mechanisms. One such MAb, Herceptin (Trastuzumab), has been approved for human
      use. We have generated a panel of murine anti-Her-2 MAbs against nine different
      epitopes on the extracellular domain of Her-2 and have evaluated the antitumor
      activity of three of these MAbs alone and in combination, both in vitro and in
      vivo. We found that MAbs (against different epitopes) make a highly effective
      mixture, which was more effective than the individual MAbs in treating s.c. tumor
      nodules of BT474 cells in SCID mice. In vitro, the MAb mixture was also more
      effective than the single MAbs in inducing antibody-dependent cellular
      cytotoxicity and complement-dependent cytotoxicity, inhibiting cell growth and
      inducing apoptosis, and inhibiting the secretion of vascular endothelial growth
      factor. Taken together, these activities might explain the superior performance
      of the MAb mixture in vivo.

PMID- 12060610
TI  - An HLA-A24-restricted cytotoxic T lymphocyte epitope of a tumor-associated
      protein, survivin.
AB  - To date an increasing number of T-cell epitopes derived from various tumor
      associated antigens have been reported, and they proved to play significant roles
      for tumor rejection both in vivo and in vitro. Survivin was originally identified
      as a member of the inhibitor of apoptosis protein family. Expression of this gene
      is developmentally regulated. Although survivin is expressed during normal fetal
      development, the expression is barely detected in terminally differentiated adult
      tissues except for testis, thymus, and placenta. In contrast, it is abundantly
      expressed in a wide variety of malignant tissues. We examined the expression of
      survivin and the two splicing variants survivin-2B and survivin-DeltaEx3 in
      various cancer cells, immortalized cells, and normal adult tissues. It was
      demonstrated that two splicing variants were detected in various types of cancer
      cells as well as survivin, and their expression was more restricted to cancer
      cells as compared with survivin expression. To identify HLA-A24-restricted T-cell
      epitopes from survivin and the variant proteins, three peptides were selected
      from amino acid sequence of these proteins, based on the HLA-A24-binding motif.
      Peptide binding assay to HLA-A24 revealed that only one peptide designated as
      survivin-2B80-88 (AYACNTSTL) was capable of binding to HLA-A24. By stimulating
      peripheral blood lymphocytes with the peptide-pulsed antigen-presenting cells,
      CTLs were successfully induced in vitro from five of five HLA-A24-positive cancer
      patients. The CTLs showed significant cytotoxicity against HLA-A24-positive
      survivin-2B-positive cancer cells. These data suggest that survivin-2B80-88 may
      be a potent T-cell epitope eliciting CTL response against a splicing variant
      survivin-2B, which is specifically expressed in many kinds of cancer cells.

PMID- 12060611
TI  - Inhibition of furin-mediated processing results in suppression of astrocytoma
      cell growth and invasiveness.
AB  - PURPOSE: Astrocytoma arises in the central nervous system as a tumor of great
      lethality, in part because of the invasive potential of the neoplastic cells that
      are able to release extracellular matrix-degrading enzymes. Furin convertase
      activates several precursor matrix metalloproteases involved in the breakdown of
      the extracellular matrix. In the present study inhibition of furin was achieved
      by gene transfer of alpha(1)-antitrypsin Portland (PDX) cDNA. EXPERIMENTAL
      DESIGN: This furin inhibitor was transfected into two tumorigenic astrocytoma
      cell lines. The inhibitory effect was evaluated using in vivo tumorigenicity,
      invasion, and proliferation assays, as well as by investigating impairment of
      furin substrate processing. RESULTS: Expression of PDX prevented the s.c. growth
      of the transfected cells. Invasion assays demonstrated that PDX-transfected cells
      exhibited a reduced invasive ability in vitro and in vivo. Furthermore, s.c.
      growth of PDX transfectant xenotransplants showed a significant reduction in size
      that coincided with a significant decrease of the in vitro doubling time and of
      the in vivo cell proliferation ability. Additional studies showed that the furin
      substrates insulin-like growth factor IR, transforming growth factor beta and
      membrane type 1-matrix metalloprotease were not activated in PDX-expressing
      astrocytoma cells. CONCLUSIONS: PDX expression in astrocytoma cells demonstrated
      a direct mechanistic link between furin inhibition, and decreased astrocytoma
      proliferation and invasive ability. Because furin inhibition inhibits both
      invasiveness and cell growth in astrocytoma, furin should be considered a
      promising target for glioblastoma therapy.

PMID- 12060612
TI  - Activated mitogen-activated protein kinase expression during human breast
      tumorigenesis and breast cancer progression.
AB  - PURPOSE: The purpose of this study is to address the hypothesis that
      activatedmitogen-activated protein kinase (MAPK; extracellular signal-regulated
      kinases 1 and 2) has a role in breast tumorigenesis, breast cancer progression,
      and the development of tamoxifen resistance. EXPERIMENTAL DESIGN: H-score
      analysis and a specific antibody for the immunohistochemical detection of
      activated MAPK in formalin-fixed, paraffin-embedded tissue sections were used to
      compare expression in: (a) human breast tumors and their matched adjacent normal
      breast tissue; (b) primary human breast tumors and their matched lymph node
      metastases; and (c) primary breast tumors from patients who later proved to be
      sensitive or resistant to tamoxifen treatment. RESULTS: Active MAPK expression
      was detected in 48% of primary human breast tumors and was significantly
      increased in tumors compared with adjacent normal breast (Wilcoxon test, P =
      0.027). A significant positive association (chi(2), P = 0.02; n = 55) was
      obtained between active MAPK and the presence of lymph node metastases. Moreover,
      increased active MAPK (Wilcoxon test, P = 0.0098) was found in concurrent lymph
      node metastases compared with primary breast tumors. No significant difference in
      active MAPK was found in primary tumors of patients who later responded to
      tamoxifen or did not respond to tamoxifen. CONCLUSIONS: These data suggest that
      active MAPK is a marker of breast cancer metastasis and has a role in the
      metastatic process. However, active MAPK is unlikely to be a marker of endocrine
      sensitivity or involved in de novo tamoxifen resistance.

PMID- 12060613
TI  - The expression of decorin in human ovarian tumors.
AB  - PURPOSE: The purpose of this study was to examine ovarian cancer cells for the
      expression of decorin, a proteoglycan component of the cell matrix that can
      inhibit cancer cell growth. EXPERIMENTAL DESIGN: Cultured ovarian cancer cells
      and surgically excised tumors were examined by immunohistochemistry and Western
      blot analysis for decorin expression. Reverse transcription-polymerase chain
      reaction analysis was used to analyze cultured cells for decorin transcripts.
      RESULTS: We detected decorin transcripts in two ovarian cancer cell lines by
      reverse transcription-polymerase chain reaction analysis. However, no decorin was
      found in conditioned culture medium from those cell lines. Cells treated with the
      proteasome inhibitor MG132 showed strong perinuclear staining with a decorin
      specific monoclonal antibody by immunohistochemistry. Also, Western blot analysis
      showed the presence of a ladder of decorin-specific bands that were intensified
      by treatment with MG132, suggesting that de novo synthesized decorin was degraded
      by the ubiquitination pathway. The decorin component of tumor stroma was
      previously shown to contain high levels of chondroitin sulfate as opposed to
      dermatan sulfate side chains, and those molecules contained unusually high levels
      of O- and 6-sulfate linkages. We provided immunohistochemical evidence that these
      chondroitin sulfate side chains may have been produced by myofibroblasts.
      CONCLUSIONS: Decorin protein expression was not detected in ovarian cancer cells.
      Decorin transcripts were produced and probably translated, but the protein was
      probably degraded by the ubiquitination pathway. We present evidence that stromal
      decorin of ovarian tumors was made by myofibroblasts. We also propose that
      decorin may be a tumor suppressor gene that is inactivated during epithelial cell
      development.

PMID- 12060615
TI  - Prognostic significance of adoptive immunotherapy with tumor-associated
      lymphocytes in patients with advanced gastric cancer: a randomized trial.
AB  - PURPOSE: We performed adoptive immunotherapy (AIT)with tumor-associated
      lymphocytes (TALs) in combination with chemotherapy in patients with advanced
      stage gastric cancer in a randomized controlled study and investigated whether or
      not an improved survival effect is observed with AIT. EXPERIMENTAL DESIGN: Forty
      four consecutive patients with stage IV gastric cancer [staged according to the
      International Union against Cancer classification] were prospectively assigned to
      the control group (chemotherapy alone) or the AIT group (AIT plus chemotherapy).
      Patients in the AIT group received an adoptive transfer of cultured TALs in
      combination with low-dose cisplatinum/5-fluorouracil chemotherapy, whereas
      patients in the control group received chemotherapy alone. RESULTS: The 50%
      survival rates were 11.5 and 8.3 months in the AIT and control groups,
      respectively. The overall survival of patients in the AIT group was significantly
      better than that of patients in the control group, as analyzed by the log-rank
      test (P < 0.05). Multivariate analysis with Cox's proportional hazards model
      revealed that AIT provided an independent prognostic factor, indicating that AIT
      influenced patient survival in a positive manner. CONCLUSIONS: AIT with TALs in
      combination with chemotherapy was effective in prolonging survival in patients
      with stage IV gastric cancer.

PMID- 12060614
TI  - Detection of gene promoter hypermethylation in the tumor and serum of patients
      with gastric carcinoma.
AB  - PURPOSE: Aberrant promoter methylation, an alternative mechanism for gene
      silencing, is frequently detected in gastric cancer. We studied the feasibility
      of detecting aberrant methylation in serum of gastric cancer patients.
      EXPERIMENTAL DESIGN: Patients (54) with gastric adenocarcinoma were studied. The
      tumor and the paired serum were examined for aberrant methylation in DAP-kinase,
      E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR. Serum from 30 age
      matched noncancer patients was used as control. RESULTS: Promoter methylation in
      DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 70.3, 75.9, 18.5,
      68.5, and 66.7% of primary tumor. In serum of gastric cancer patients,
      methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 were detected in 48.1,
      57.4, 14.8, 55.6, and 51.9%, respectively. None of the control serum showed
      aberrant methylation. Aberrant methylation in serum DNA was all accompanied with
      methylation in the corresponding tumor samples. In general, >60% of serum from
      cancers with aberrant methylation demonstrated these epigenetic alterations.
      CONCLUSION: Our findings suggest that aberrant promoter methylation in serum can
      be detected in a substantial proportion of gastric cancer patients, and this
      strategy should be evaluated in the screening and surveillance of gastric cancer.

PMID- 12060616
TI  - A short-term dietary supplementation of high doses of vitamin E increases T
      helper 1 cytokine production in patients with advanced colorectal cancer.
AB  - PURPOSE: Patients with advanced cancer exhibit multifaceted defects in their
      immune capacity, which are likely to contribute to an increased susceptibility to
      infections and disease progression and to constitute a barrier to
      immunotherapeutic interventions. A chronic inflammatory condition associated with
      increased oxidative stress has been suggested as one of the responsible
      mechanisms behind the tumor-induced immune suppression. We, therefore, speculated
      that supplementation with the antioxidant vitamin E could enhance the immune
      functions in patients with advanced cancer. EXPERIMENTAL DESIGN: This hypothesis
      was here tested in twelve patients with colorectal cancer (Dukes' C and D) who,
      prior to intervention with chemo- or radiotherapy, received a daily dose of 750
      mg of vitamin E during a period of 2 weeks. RESULTS: Short-term supplementation
      with high doses of dietary vitamin E leads to increased CD4:CD8 ratios and to
      enhanced capacity by their T cells to produce the T helper 1 cytokines
      interleukin 2 and IFN-gamma. In 10 of 12 patients, an increase of 10% or more
      (average, 22%) in the number of T cells producing interleukin 2 was seen after 2
      weeks of vitamin E supplementation, as compared with peripheral blood monocyte
      samples taken before treatment (P = 0.02). Interestingly, there seemed to be a
      more pronounced stimulatory effect by vitamin E on naive (CD45RA(+)) T helper
      cells as compared with T cells with a memory/activated phenotype. CONCLUSIONS:
      Dietary vitamin E may be used to improve the immune functions in patients with
      advanced cancer, as a supplement to more specific immune interventions.

PMID- 12060617
TI  - A Phase I study with an anti-CD30 ricin A-chain immunotoxin (Ki-4.dgA) in
      patients with refractory CD30+ Hodgkin's and non-Hodgkin's lymphoma.
AB  - Ki-4.dgA is an anti-CD30 immunotoxin (IT) constructed by coupling the monoclonal
      antibody Ki-4 via a sterically hindered disulfide linker to deglycosylated ricin
      A-chain. This IT was efficacious in vitro and in SCID mice with disseminated
      human Hodgkin's lymphoma. Accordingly, a Phase I trial in patients (pts) with
      Hodgkin's lymphoma was designed. The objectives of this Phase I trial were to
      determine the maximum tolerated dose, the dose-limiting toxicities,
      pharmacokinetics, and antitumor activity. Seventeen pts with relapsed CD30+
      lymphoma were treated with escalating doses (5, 7.5, or 10 mg/m(2)/cycle) of the
      IT as four bolus infusions on days 1, 3, 5, and 7 for one to three cycles. All of
      the pts had progressive disease and were heavily pretreated. Nine had primary
      progressive disease and 14 had advanced disease with massive tumor burdens. The
      mean age was 35 years (24-52 years). Peak serum concentrations of the intact IT
      varied from 0.23 to 1.1 microg/ml. Side effects and dose-limiting toxicities were
      related to vascular leak syndrome, i.e., decreases in serum albumin, edema,
      weight gain, hypotension, tachycardia, myalgia, and weakness. The maximum
      tolerated dose was 5 mg/m(2). Seven of 17 (40%) pts made human antiricin
      antibodies (> or =1.0 microg/ml), and 1 pt developed human antimouse antibodies
      (> or =1.0 microg/ml). Clinical response in the 15 evaluable pts included 1
      partial remission, 1 minor response, and 2 stable diseases. In conclusion, the IT
      was less well tolerated than other ITs of this type. This might be because of the
      low number of CD30+ peripheral blood mononuclear cells, and in part because of
      binding of the IT to soluble CD30 antigen and the resulting circulation of
      IT/sCD30 complexes.

PMID- 12060618
TI  - Alterations in the frequency of dendritic cell subsets in the peripheral
      circulation of patients with squamous cell carcinomas of the head and neck.
AB  - Patients with advanced squamous cell carcinomas of the head and neck (SCCHN) are
      frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting
      cells that play a role in antitumor immune responses. Using multicolor flow
      cytometry, the percentages of lineage-negative (LIN(-)) and DR(+) DC precursors,
      as well as their LIN(-)DR(+)CD11c(+) (myeloid) and LIN(-)DR(+)CD123(+) (lymphoid)
      subsets, were determined in the peripheral blood of 36 patients with SCCHN before
      surgery. Peripheral blood mononuclear cells of 28 age- and sex-matched healthy
      individuals were used as controls. The proportions of LIN(-)DR(+) cells were
      found to be comparable in the circulation of patients and controls. However, the
      relative level of DR expression in LIN(-)DR(+) DC was lower in patients than in
      controls, suggesting a difference in the maturity of DC. The relative proportion
      of LIN(-)DR(+)CD123(+) cells in the LIN(-)DR(+) subset of DC did not differ
      significantly in patients compared with normal individuals. However, the
      percentage of myeloid-derived LIN(-)DR(+)CD11c(+) DCs was significantly lower (P
      < 0.002) in SCCHN patients than in controls. Of the 13 patients who were
      restudied 6 weeks after surgery, 9 showed an increase of the myeloid-derived LIN(
      )DR(+)CD11c(+) DC subset postoperatively. This observation suggests that
      deficiency in the myeloid-derived DC precursors in patients with SCCHN is related
      to the presence of tumor and is reversible. An overall decrease in the myeloid
      derived subset of DC could contribute to the failure of SCCHN patients to develop
      effective antitumor immune responses.

PMID- 12060619
TI  - Reverse transcription-polymerase chain reaction detection of prostate-specific
      antigen, prostate-specific membrane antigen, and prostate stem cell antigen in
      one milliliter of peripheral blood: value for the staging of prostate cancer.
AB  - PURPOSE: There have been several studies on the presence of circulating tumor
      cells in the peripheral blood of patients with malignant tumors including
      prostate cancer (PCa) using reverse transcription-PCR (RT-PCR). One of the aims
      of these studies was to obtain high sensitivity that would enable early-stage
      diagnosis. However, they varied in their detection rates, and the methods were
      rather complicated. We have improved the RT-PCR assay combining three prostate
      associated molecules, prostate specific antigen (PSA), prostate specific membrane
      antigen (PSMA), and prostate stem cell antigen (PSCA) to reveal patients with
      poor prognosis. EXPERIMENTAL DESIGN: Peripheral blood samples were obtained from
      129 patients including 58 cases of PCa and 71 cases of nonmalignant disorders.
      Total RNA was extracted from 1 ml of whole blood using a commercially available
      kit. RESULTS: The sensitivity of PSA-, PSMA-, and PSCA-nested RT-PCR was verified
      with positive signals of a single LNCaP cell in 1 ml of female blood sample. PSA
      , PSMA-, and PSCA-mRNA were detected in 7 (12.1%), 12 (20.7%), and 8 (13.8%) PCa,
      and in 1, 2, and 0 samples in nonmalignant disorders, respectively. Among 58 PCa
      patients, each PCR indicated the prognostic value in the hierarchy of
      PSCA>PSA>PSMA RT-PCR, and extraprostatic cases with positive PSCA PCR indicated
      lower disease-progression-free survival than those with negative PSCA PCR.
      CONCLUSIONS: The present findings suggest that PSCA PCR would be most promising
      for the molecular staging of PCa. The present RT-PCR is a highly cost-effective
      and rapid procedure, enabling the molecular staging of PCa with RT-PCR as a
      diagnostic routine.

PMID- 12060620
TI  - A novel gene from the human endogenous retrovirus K expressed in transformed
      cells.
AB  - PURPOSE: We investigated the expression of human endogenous retrovirus K (HERV-K)
      transcripts in various tumor tissues and transformed cell lines. EXPERIMENTAL
      DESIGN: We performed reverse transcription-PCR analysis to examine expression of
      env reading frame transcripts in mammary carcinoma biopsies, germ-cell tumor
      samples, ovarian carcinomas, and lymphocytes of leukemic patients, as well as in
      a variety of transformed cell lines. The novel np9 gene was analyzed by
      sequencing. Expression of the recombinant Np9 protein was shown by Western blot
      analysis and immunofluorescence studies with polyclonal Np9-specific antibodies.
      Subcellular localization was determined with a Np9-enhanced-green fluorescence
      protein fusion protein, and the effects of Np9 on cell proliferation and survival
      were studied in growth and standard colony formation assays. RESULTS: We have
      identified a novel gene, np9, within the HERV-K env-reading frame that gives rise
      to a 9-kDa protein localized predominantly in the cell nucleus. np9 transcript
      results from a novel, HERV-K type 1-specific splice donor site and is expressed
      in various tumor tissues and transformed cell lines but not in normal,
      nontransformed cells. CONCLUSION: The highly specific expression of np9 in tumor
      tissue suggests that the protein may possess a function in tumorigenesis.

PMID- 12060621
TI  - Expression of cell-cycle-regulated proteins pRb2/p130, p107, p27(kip1), p53, mdm
      2, and Ki-67 (MIB-1) in prostatic gland adenocarcinoma.
AB  - PURPOSE: The quest for prognostic molecular markers in prostatic carcinoma is
      still in progress. Many proteins have already been screened by
      immunohistochemistry with the aim to find the most reliable indicator of
      progressive disease. In this study, we evaluated the expression of pRb2/p130,
      p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24
      prostate carcinomas compared with the paired expression of normal prostates.
      EXPERIMENTAL DESIGN: Expression of the different proteins in normal and
      pathological specimens was evaluated by the Wilcoxon test. A matrix of
      correlation (Spearman coefficient) was used to evaluate the possible association
      in expression among the different proteins. Logistic regression analysis was used
      to test the multivariable prognostic value of the levels of protein expression
      for the probability of disease development. RESULTS: p53 and Ki-67 (MIB-1) showed
      a higher expression in cancer than in normal tissue (P = 0.006 and <0.001,
      respectively). pRb2/p130, p107, and p27(kip1) showed an overall lower expression
      in cancer, but the difference between cytoplasmic and nuclear expression was
      always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower
      in cancer, but the difference between cytoplasmic and nuclear expression was not
      significant (P = 0.571) when compared with that in normal tissue. A positive
      correlation between p27 and pRb2/p130 levels expressed, in normal and cancer
      counterparts in the same sample, as the difference between cytoplasmic and
      nuclear protein concentrations (P = 0.045) was found. Additionally, p107
      expression showed an inverse correlation with Ki-67 (MIB-1) expression in the
      most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67
      (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear
      concentrations) were the variables associated with a higher risk of cancer. The
      highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by
      pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity
      (rate of cases having a posterior probability of disease >/=0.5) of 61% with a
      false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and
      a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a
      sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen
      in which we also found a high-grade prostatic intraepithelial neoplasia showed
      the progressive loss of pRb2/p130 from normal prostatic cells to prostatic
      intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of
      expression of the tumor suppressor gene pRb2/p130 could be involved in the
      progression of the disease, from an early stage. CONCLUSIONS: This study showed
      that all of the proteins but mdm-2 were expressed at a different rate in normal
      and pathological prostate specimens. Multivariate analysis showed that pRb2/p130
      and p107 may be involved in the pathogenesis and progression of prostate cancers,
      and that the expression of the retinoblastoma-related protein pRb2/p130 along
      with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear
      concentrations, could be considered new parameters to be evaluated in
      discriminating patients at a higher risk for prostate cancer.

PMID- 12060622
TI  - Changes in microvessel density as assessed by CD34 antibodies after primary
      chemotherapy in human breast cancer.
AB  - BACKGROUND: Several papers have shown that quantitationof tumor angiogenesis in
      primary breast cancer by counting blood vessels gives an independent assessment
      of prognosis. The impact of chemotherapy +/- endocrine therapy on the extent of
      angiogenesis is unknown. METHODS: Matched pair histological tumor samples were
      obtained before and after primary chemotherapy from 120 breast cancer patients
      recruited in the same institution. The first 55 cases received cyclophosphamide,
      methotrexate, and 5-fluorouracil +/- Tamoxifen, whereas the subsequent 65 were
      submitted to single agent epirubicin. Patients underwent an incisional biopsy at
      diagnosis and definitive surgery on completion of three or four chemotherapy
      cycles. Microvessel density (MVD) was performed after staining with the CD34
      monoclonal antibody. RESULTS: MVD slightly decreased after chemotherapy [median
      51.26 mm(2) (range 2.33-163.1) and 44.27 mm(2) (2.33-121.16; P < 0.001)]; this
      small reduction neither correlated with tumor response nor with changes in Ki67
      expression. MVD at baseline significantly correlated with MVD assessed at
      definitive surgery (Spearman r = 0.70, P < 0.001). In multivariate analysis, c
      erbB2 status showed an independent role in predicting the reduction in MVD that
      just failed to attain the statistical significance (P = 0.08), whereas baseline
      parameters, such as T, N, steroid hormone receptor, bcl-2, p53, c-erbB2, and Ki67
      expression, did not enter the model. CONCLUSIONS: Primary chemotherapy is able to
      modestly reduce the MVD in breast tumors. This small change is not biologically
      important, because the baseline neoangiogenesis status is not substantially
      changed. The change in microvessel count after chemotherapy could be potentially
      influenced by the c-erbB2 status.

PMID- 12060624
TI  - Overexpression of hypoxia-inducible factor 1alpha is associated with an
      unfavorable prognosis in lymph node-positive breast cancer.
AB  - PURPOSE: Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that
      supports the adaptation of human cancer cells to hypoxia and is involved in
      various pathways supporting tumor growth and progression. The aim of this study
      was to determine the prognostic influence of HIF-1alpha expression in patients
      with advanced-stage breast cancer, evident by positive lymph nodes. EXPERIMENTAL
      DESIGN: Expression of HIF-1alpha was determined immunohistochemically in 206
      patients with lymph node-positive breast cancer. Furthermore, the
      interrelationship of HIF-1alpha with p53 and HER-2 protein expression, estrogen
      receptor density, and survival was analyzed. Colocalization of p53 and HIF-1alpha
      proteins was analyzed by confocal laser scanning microscopy. RESULTS: Strong
      nuclear expression of HIF-1alpha by invasive cancer cells was found in 48
      patients (23.3%), moderate expression was found in 74 patients (35.9%), and weak
      expression was found in 35 patients (17%); no expression was observed in 49
      patients (23.8%). HIF-1alpha protein overexpression was associated with
      significantly shorter overall and disease-free survival time (P = 0.003 and P =
      0.001, respectively; Cox regression analysis). No correlation of HIF-1alpha and
      HER-2 expression or estrogen receptor density was observed. CONCLUSIONS: This
      study shows that HIF-1alpha is an independent prognostic factor for an
      unfavorable prognosis in patients with lymph node-positive breast cancer. Our
      results indicate that patients with advanced-stage breast cancers might profit
      from future therapies targeting HIF-1alpha.

PMID- 12060623
TI  - Insulin-like growth factor I receptor activity in human medulloblastomas.
AB  - Medulloblastomas represent about 25% of all pediatric intracranial neoplasms.
      These highly malignant tumors arise from the cerebellum affecting mainly children
      between ages 5 and 15. Although the etiology of medulloblastomas has not yet been
      elucidated, several reports suggest that insulin-like growth factor I (IGF-I) may
      contribute to the development of these tumors. Results of this study show that
      the majority of cases examined were characterized by the abundant presence of the
      receptor for IGF-I (IGF-IR) protein (16 of 20 cases), and its major signaling
      molecule, insulin receptor substrate 1 (IRS-1; 15 of 20). Protein levels for IGF
      IR and IRS-1, determined by Western blot and immunohistochemistry, were
      significantly higher in medulloblastoma biopsies than in control cerebellar
      tissue. By immunohistochemistry, 10 of 17 biopsies examined were also positive
      for the anti-pY1316 antibody staining that specifically recognizes the
      phosphorylated (active) form of the IGF-IR. These findings correlate with the
      fact that phosphorylated forms of the downstream-signaling molecules Erk-1, Erk
      2, and Akt/protein kinase B were found in medulloblastoma biopsies but not in
      control cerebellar tissue. Importantly, there is a strong inverse correlation
      between biopsies that are positive for anti-pY1316 and for anti-Trk-C
      immunoreactivity. These observations direct our attention to the IGF-IR system as
      a potential therapeutic target in medulloblastomas and suggest a possibility of
      using the anti-pY1316 antibody as a potential prognostic marker for
      medulloblastomas.

PMID- 12060625
TI  - Smad4 and transforming growth factor beta1 expression in patients with squamous
      cell carcinoma of the esophagus.
AB  - PURPOSE: The members of the Smad family play key rolesin regulating gene
      expression in the transforming growth factor (TGF)-beta1 signaling pathways.
      Activation of Smads causes their translocation from the cytoplasm to the nucleus,
      where they function as transcription factors. The present study analyzed the
      expression and clinicopathological significance of Smad4 and TGF-beta1 in
      squamous cell carcinoma of the esophagus. EXPERIMENTAL DESIGN:
      Immunohistochemistry was used to investigate the expression of Smad4 and TGF
      beta1 proteins in 258 patients with squamous cell carcinoma of the esophagus. The
      relationship between expression of these proteins and clinicopathological factors
      was analyzed, and the usefulness of Smad4 in disease prognosis was evaluated in
      relation to TGF-beta1 expression. RESULTS: Smad4 expression was preserved in
      32.2% of tumors, and TGF-beta1 expression was identified in 42.6% of tumors.
      Patients with preserved expression of Smad4 had a higher rate of early-stage
      carcinoma (P < 0.01) and fewer lymph node metastases (P < 0.01) than those with
      reduced Smad4 expression. The expression of TGF-beta1 was not associated with any
      of the clinicopathological factors. Postoperative survival analysis indicated
      that patients with a tumor in which Smad4 expression was reduced had worse
      clinical outcomes than those with preserved expression (P = 0.01). In patients
      with TGF-beta1-negative tumors, the survival rate was significantly higher in
      patients with a preserved level of Smad4 expression than in those with reduced
      Smad4 expression (P = 0.02). However, according to multivariate analysis, Smad4
      expression could not be used as an independent prognostic factor. CONCLUSIONS:
      Although Smad4 expression could not be used as a prognostic factor, its
      expression reflected tumor progression such as tumor depth and lymph node
      metastasis.

PMID- 12060626
TI  - Expression profile of genes in non-small cell lung carcinomas from long-term
      surviving patients.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) is usually associated with a poor
      prognosis. Some patients survive their disease, and the underlying molecular
      mechanisms are still poorly understood. The purpose of this investigation was to
      evaluate expression profiles of proteins determining the survival of NSCLC
      patients for 5 years. EXPERIMENTAL DESIGN: The expression of 21 gene products was
      evaluated immunohistochemically in paraffinembedded primary NSCLCs from 216
      patients. The data were correlated with the survival times of the patients
      (survival of more or less than 5 years) by means of chi(2) test and hierarchical
      cluster analysis. RESULTS: The relationships of patients' survival and 21
      parameters were determined including oncogene and tumor suppressor products and
      proliferative, apoptotic, and angiogenic factors. FOS, P53, RAS, ERBB1, JUN,
      PCNA, cyclin A, FAS/CD95, and HIF-1beta revealed a correlation to survival. In a
      second step, these nine parameters were further analyzed by hierarchical cluster
      analyses of all patients, of stage III patients, and of patients with squamous
      cell lung carcinomas. We identified clusters with significantly more long-term
      survivors. The expression of FOS, JUN, ERBB1, and cyclin A or PCNA were decreased
      in carcinomas of patients with long-term survival. CONCLUSIONS: The expression
      profile of these factors predicts a significantly better long-term outcome of
      NSCLC patients. This may have implications for the development of individualized
      therapy options in the future.

PMID- 12060627
TI  - Evaluation of the family history collection process and the accuracy of cancer
      reporting among a series of women with endometrial cancer.
AB  - Family history data are critical in the study of hereditary cancer syndromes and
      the identification of cancer modifier genes. PURPOSE: The purpose of this study
      was to analyze the process for collecting and verifying reported cancer family
      histories and identify reporting inaccuracies among a series of women with
      endometrial cancer. EXPERIMENTAL DESIGN: Detailed family histories were obtained
      from 80 women enrolled in a research study. Medical records were collected to
      verify cancer reporting. RESULTS: Participants reported 289 cancers among
      themselves and 2925 first-, second-, and third-degree relatives. There was a
      significant relationship between the number of telephone contacts made with each
      participant and the fraction of records retrieved from hospitals (chi(2) = 23.68,
      d.f. = 7, P = 0.001). Medical records were retrieved for 102 of 289 (35%)
      reported cancers and 10 additional cancers, not initially reported by
      participants. Medical records were more likely to be retrieved if the relative
      with cancer was living, closely related to the study participant, and the cancer
      type was known. The success in retrieving medical records declined with
      increasing record age (chi(2) = 35.07, d.f. = 5, P < 0.001). Thirty-two of the
      112 (28.6%) verified cancers were identified to be inaccurately reported, with a
      significantly higher number of inaccurate reports among second- and third-degree
      relatives than first-degree relatives (P = 0.02). Two participants, who did not
      accurately report their cancer family history, had an increase in their family
      based risk assessment after medical record collection. CONCLUSIONS: Additional
      studies to improve record collection efficiency and identify cancer reporting
      accuracy are needed among general research populations.

PMID- 12060628
TI  - Cyclooxygenase-2 expression is a novel prognostic factor in malignant
      mesothelioma.
AB  - Malignant mesothelioma (MM) is a fatal tumor of increasing incidence, which is
      resistant to current therapy. Cyclooxygenase-2 (COX-2) plays an important role in
      solid tumor growth, invasiveness, and angiogenesis, in part through the synthesis
      of prostaglandins such as prostaglandin E(2) (PGE(2)). In a prospective study, we
      evaluated COX-2 expression in snap-frozen, surgically resected MM tissue
      specimens using immunohistochemistry and semiquantitative Western blotting.
      PGE(2) was assessed by enzyme immunoassay. Thirty epithelioid, 10 biphasic, and 8
      sarcomatoid tumors were evaluated. Immunohistochemistry demonstrated strong
      cytoplasmic tumor cell and variable stromal staining in all of the cases. COX-2
      protein levels were correlated with clinicopathological prognostic factors using
      Kaplan-Meier and Cox proportional hazards models. High COX-2 band densitometry
      values correlated with poor survival (P = 0.008). In multivariate analysis, high
      COX-2 expression (P = 0.0005), nonepithelioid cell type (P = 0.002), and chest
      pain (P = 0.04) were independent predictors of poor prognosis. Furthermore, COX-2
      expression contributed in multivariate analysis to both European Organization for
      Research and Treatment of Cancer (P = 0.001) and Cancer and Leukemia Group B (P =
      0.003) prognostic scoring systems. The presence of PGE(2) was demonstrated in all
      of the samples. These results suggest that COX-2 expression is a prognostic
      factor in MM. COX-2 is a potential therapeutic target in MM, and trials are
      required of COX-2 inhibitors alone or in combination with existing treatment
      modalities.

PMID- 12060630
TI  - Detection of circulating breast tumor cells by differential expression of marker
      genes.
AB  - PURPOSE: We undertook a systematic approach to identify breast cancer (BC) marker
      genes with molecular assays and evaluated these marker genes for the detection of
      minimal residual disease in peripheral blood mononuclear cells (PBMCs).
      EXPERIMENTAL DESIGN: We used serial analysis of gene expression to identify a
      range of genes that were expressed in BC but absent in the expression profiles of
      blood and bone marrow cells. Next, we evaluated a panel of four marker genes
      (p1B, PS2, CK19, and EGP2) by real-time quantitative PCR in 103 PBMC samples from
      patients with metastatic BC (stage III/IV) and in 96 PBMC samples from healthy
      females. RESULTS: Increased marker gene expression of at least one marker was
      seen in 33 of 103 patients. Using quadratic discriminant analysis including all
      four marker genes, we determined a discriminant value with 29% positivity in the
      BC patient group that did not yield false positive results among the healthy
      females. CONCLUSIONS: Real-time PCR for the simultaneous expression of multiple
      cancer-specific genes may ensure the specificity required for the clinical
      application of mRNA expression-based assays for occult tumor cells.

PMID- 12060631
TI  - Prognostic significance of preoperative molecular serum analysis in renal cancer.
AB  - PURPOSE: We evaluated the postoperative clinical course of patients with renal
      cancer identified preoperatively by microsatellite analysis to examine the
      correlation between microsatellite alterations and risk of disease recurrence and
      patient mortality 2 years after nephrectomy. EXPERIMENTAL DESIGN: A panel of 28
      microsatellite markers was used previously to assess loss of heterozygosity and
      microsatellite instability in urine, serum, and tumor DNA of 30 patients with
      clinically organ-confined renal masses who underwent partial or radical
      nephrectomy. The clinical reports and imaging data in the medical records of
      patients with a minimum follow-up of 2 years were retrospectively reviewed to
      determine their postoperative course. RESULTS: Two-year follow-up was available
      for the 30 patients (100%) who entered the study. Mean age was 61.6 +/- 12.9
      years (range, 21-77 years). Tumor stage was associated with patient mortality (P
      = 0.03). Tumor grade was associated with mortality (P = 0.03) and disease
      recurrence (P < 0.01). The frequency of microsatellite alterations (loss of
      heterozygosity) found in the preoperative serum of patients with renal masses
      served as a prognostic indicator for disease recurrence (P < 0.01). CONCLUSIONS:
      Analysis of microsatellite alterations found in preoperative blood samples is a
      promising method for the detection of renal cancer. The presence of frequent
      molecular changes in preoperative serum was associated with disease recurrence.
      These findings suggest a role for microsatellite analysis in future studies
      attempting to stratify patients with clinically organ-confined renal cancer into
      low- and high-risk prognostic groups. Larger prospective randomized trials are
      needed to validate the clinical utility of this observation.

PMID- 12060629
TI  - The prognostic value of angiogenesis and metastasis-related genes for progression
      of transitional cell carcinoma of the renal pelvis and ureter.
AB  - PURPOSE: We reported previously that angiogenesis evaluated by intratumor
      microvessel density (MVD), expression of such angiogenic factors as vascular
      endothelial cell growth factor (VEGF) and basic fibroblast growth factor (bFGF),
      and the matrix metalloproteinase-9:E-cadherin ratio (M:E ratio) could identify
      patients with advanced transitional cell carcinoma (TCC) of the bladder for whom
      chemotherapy and cystectomy will be unsuccessful. In the present study, we
      evaluated the significance of the M:E ratio as a predictor for prognosis for
      patients with TCC in the upper urinary tract (TCC-UUT). EXPERIMENTAL DESIGN: We
      evaluated MVD by immunohistochemistry and the expression of angiogenic and
      metastasis-related factors by in situ hybridization in 55 nephroureterectomy
      specimens from patients who received no neoadjuvant therapy. The expression of
      angiogenesis, angiogenic and metastasis-related factors, and clinicopathological
      characteristics were evaluated for their correlation with metastasis, recurrence,
      and disease prognosis. RESULTS: We found that tumor grade and pathological stage
      were important predictors for metastasis and survival in these patients. The
      expression level of matrix metalloproteinase type 9 (MMP-9) and type 2 (MMP-2)
      and the M:E ratio correlated with MVD. Increased MVD, elevated expression levels
      of MMP-9 and MMP-2, and a higher M:E ratio were associated with poor prognosis.
      Moreover, lower expression levels of E-cadherin were associated with fewer
      recurrences in the urinary bladder. Multivariate analysis indicated that the M:E
      ratio and E-cadherin expression were independent prognostic factors for disease
      progression and intravesical recurrence, respectively. CONCLUSION: We suggest
      that the M:E ratio and E-cadherin expression may be targets for novel therapeutic
      strategies.

PMID- 12060632
TI  - Loss of DCC gene expression is of prognostic importance in acute myelogenous
      leukemia.
AB  - PURPOSE: Expression of the deleted in colorectal carcinoma (DCC) gene has been
      found to be lost in some patients with acute myelogenous leukemia (AML). Although
      this finding is critical to leukemogenesis, its prognostic significance remains
      uncertain. To evaluate this, loss of DCC gene expression in AML patients and
      their prognostic significance were investigated. EXPERIMENTAL DESIGN: A group of
      170 patients with AML was analyzed. DCC gene expression in AML cells was
      determined by a semiquantitative reverse transcriptase-PCR. Simultaneous mutation
      analyses of the p53, N-ras, and FLT3 genes were performed in all of the AML cells
      by single-strand conformation polymorphism and sequencing subsequent to PCR. The
      importance of loss of DCC expression was evaluated by Cox proportional analysis
      and the Kaplan-Meier method. RESULTS: Loss of DCC expression was detected in 47
      patients (27.6%). The p53, N-ras, and FLT3 mutations were detected in 20 (11.7%),
      42 (24.7%), and 26 (15.2%) patients, respectively. The durations of overall
      survival (OS) and complete remission (CR) of the 47 DCC-negative AML patients
      were significantly shorter than that of the 123 DCC-positive patients (P < 0.0045
      and <0.0060, respectively). Univariate and multivariate analyses showed that loss
      of DCC expression was an unfavorable prognostic factor for both OS (P < 0.0053
      and <0.0084, respectively) and CR duration (P < 0.0146 and <0.0371,
      respectively). The 64 DCC-positive patients with wild p53, N-ras, and FLT3 had
      statistically better CR attainment compared with the other 106 patients (P <
      0.0001). CONCLUSIONS: Loss of DCC gene expression was shown to be an independent
      prognostic factor in AML patients. Thus, loss of DCC gene expression might serve
      as an important molecular marker for predicting the CR duration and OS of
      patients with AML.

PMID- 12060633
TI  - Prognostic significance of metallothionein in human gastrointestinal cancer.
AB  - PURPOSE: Metallothionein (MT) is a small protein with a high affinity for
      divalent heavy metal ions. This metalloproteinis involved in many
      (patho)physiological processes, like metal homeostasis and detoxification, cell
      proliferation, apoptosis, therapy resistance, and protection against oxidative
      damage. Alterations in the immunohistochemical expression of MT have been
      reported for various human tumors, and a high expression has been found to be
      associated with a poor clinical outcome. We showed previously that
      gastrointestinal cancer is accompanied by a decrease in MT expression, but the
      most malignant phenotypes had the highest MT levels. The purpose of the present
      study was to assess the clinical relevance of MT in gastrointestinal cancer.
      EXPERIMENTAL DESIGN: In this study, we determined the MT levels, by
      radioimmunoassay, in intestinal tissue of 251 patients with colorectal cancer and
      81 patients with gastric cancer and assessed the relation with the overall
      survival of these patients. RESULTS: More than 74% of the carcinomas were found
      to have a lower MT level than their corresponding normal mucosa. In colorectal
      cancer patients, but not in gastric cancer patients, a high MT level in both the
      carcinomas and normal mucosa was, however, significantly associated with a poor
      overall survival, independently from clinicopathological features. CONCLUSIONS:
      Overexpression of MT in intestinal tissue of colorectal cancer patients is a
      prognostic marker for a poor overall survival. In gastric cancer, however, MT
      expression in the gastric mucosa is not of prognostic significance. This
      observation emphasizes the clinical relevance of this multifunctional
      metalloprotein in colorectal carcinogenesis and therapy.

PMID- 12060634
TI  - DNA methylation patterns at relapse in adult acute lymphocytic leukemia.
AB  - PURPOSE: Aberrant DNA methylation of promoter-associated CpG islands is an
      epigenetic DNA modification observed in acute leukemias that in certain cases has
      been associated with a poor prognosis and increased relapse rates. To study the
      role of DNA methylation in relapse mechanisms in acute lymphocytic leukemia
      (ALL), we have compared the methylation status of five genes at the time of
      initial presentation and at first relapse in 25 adult patients with ALL.
      EXPERIMENTAL DESIGN: Genes studied included the estrogen receptor (ER), multidrug
      resistance gene 1 (MDR1), p73, p15, and p16. DNA was extracted from paraffin
      embedded bone marrow biopsies. DNA methylation was analyzed using PCR of
      bisulfite-modified DNA. RESULTS: Results indicate that methylation at the time of
      relapse was stable in 92% of patients for p73, 88% for ER, 80% for p16, 72% for
      MDR1, and 60% for p15. Only one case had p16 methylation at initial presentation,
      whereas 6 patients (P = 0.0001) had methylation at relapse. Three cases had
      concomitant methylation of p15 and p16 at relapse. The degree of MDR1 methylation
      inversely correlated with the presence of MDR1 expression as detected by
      immunohistochemistry. Eighteen patients (72%) had acquired no or one methylation
      change, whereas the rest (28%) had methylation changes in two or three genes. No
      clinical-biological correlations were found between methylation of any particular
      gene or pattern. CONCLUSIONS: In summary, DNA methylation patterns are stable in
      a majority of patients with relapsed ALL, but a subset of patients acquire new
      methylation changes, in particular affecting cell cycle regulatory genes.

PMID- 12060635
TI  - Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis
      of human prostate cancer cells.
AB  - PURPOSE: The purpose of this study was to determine the effects of adenoviral
      transgene expression of MMAC/PTEN on the in vitro and in vivo growth and survival
      of PC3 human prostate cancer cells. EXPERIMENTAL DESIGN: Adenoviruses expressing
      MMAC/PTEN or green fluorescent protein as a control were introduced into PC3
      cells, and effects on signal transduction pathways and growth of tumors in an
      orthotopic nude mouse model were determined. RESULTS: MMAC/PTEN expression in PC3
      cells decreased the level of phospho Akt but not that of phospho Mapk or FAK.
      Expression of MMAC/PTEN inhibited the in vitro growth of PC3 cells primarily by
      blocking cell cycle progression. Ex vivo introduction of MMAC/PTEN expression did
      not inhibit the tumorigenicity of orthotopically implanted PC3 cells, but it did
      significantly reduce tumor size and completely inhibited the formation of
      metastases. In vivo treatment of pre-established orthotopic PC3 tumors with
      adenoviral MMAC/PTEN did not significantly reduce local tumor size, but it did
      diminish metastasis formation. CONCLUSIONS: MMAC/PTEN functionally regulates
      prostate cancer cell metastatic potential in an in vivo model system and may be
      an important biological marker and therapeutic target for human prostate cancer.

PMID- 12060636
TI  - Soluble coxsackievirus adenovirus receptor is a putative inhibitor of adenoviral
      gene transfer in the tumor milieu.
AB  - PURPOSE: Several barriers that collectively restrict gene delivery by viral
      vectors in vivo have been described. Previously, we identified soluble
      chondroitin sulfate-proteoglycans/glycosaminoglycans in malignant pleural
      effusions (MPEs) as inhibitors of retroviral vector transduction. Soluble
      components of MPE also inhibited adenoviral (Ad) gene transfer, and the factors
      were characteristically filterable, titrable, stable at 56 degrees C, and blocked
      the binding of Ad to target cells. Depleting immunoglobulin from MPE, partially
      reversed the block to Ad transduction, instigating a search for additional
      factors that bound Ad in MPE. EXPERIMENTAL DESIGN: Vector-protein interactions
      were identified after the resolution of MPE-components by SDS-PAGE. Viral
      overlays and immunoblots delineated significant interactions, and the potential
      relevance of those interactions was tested in transduction efficiency bioassays.
      RESULTS: Immunoglobulin is the predominant factor inhibiting Ad gene transfer in
      MPE. Albumin also interacted with Ad, although at predicted serum concentrations,
      it did not effect Ad transduction efficiency in vitro. Soluble coxsackievirus-Ad
      receptor (sCAR) was then identified in MPE. In a survey of 18 MPE, the mean
      concentration of sCAR was variable and estimated to be 3.51 +/- 5.02 ng/ml by
      ELISA. The impact of sCAR on transduction efficiency in this milieu was next
      assessed. Whereas immunodepletion of sCAR from MPE by affinity chromatography
      resulted in enhanced gene transfer within MPE, the inhibition of adenoviral gene
      transfer was not evident when the predicted concentrations of recombinant sCAR
      were added into the transduction medium. CONCLUSIONS: These studies indicate
      that, in addition to anti-Ad antibodies, other specific and nonspecific factors
      interact with viral vectors and may impair gene transfer in the tumor milieu. The
      presence of sCAR in MPE puts forward the notion that in certain contexts (e.g.,
      within the extracellular matrix of solid tumors) the concentrations of secreted
      (or shed) CAR may be high enough to effectively compete with Ad gene delivery.

PMID- 12060637
TI  - The neurotrophin-trk receptor axes are critical for the growth and progression of
      human prostatic carcinoma and pancreatic ductal adenocarcinoma xenografts in nude
      mice.
AB  - PURPOSE: Aberrant expression of trk receptor kinases and enhanced expression of
      various neurotrophins (NTs) have been implicated in the development and
      progression of human prostatic carcinoma and pancreatic ductal adenocarcinoma. We
      examined the antitumor efficacy of administration of NT neutralizing antibodies
      on the growth of established human prostatic carcinoma and pancreatic ductal
      adenocarcinoma xenografts in nude mice. EXPERIMENTAL DESIGN: In initial studies,
      tumor-bearing nude mice were treated with a mixture of NT antibodies [100 microg
      each of anti-nerve growth factor (NGF), anti-brain-derived neurotrophic factor,
      anti-NT-3, and anti-NT-4/5] or normal rabbit IgG (400 microg) intratumorally and
      peritumorally three times/week over a 15-day dosing period. In subsequent
      studies, tumor-bearing nude mice were treated with individual NT antibodies (100
      microg), affinity-purified anti-NGF (0.1, 1.0, or 10.0 microg), or normal rabbit
      IgG (100 microg) using the same dosing schedule. RESULTS: Treatment with the
      antibody mixture inhibited significantly the growth of TSU-Pr1 and AsPC-1
      xenografts as compared with IgG-treated controls (maximal inhibition of 53 and
      53%, respectively), whereas this treatment caused significant regression in PC-3
      xenografts. Treatment of TSU-Pr1 xenografts with either anti-NGF or anti-NT-3
      resulted in maximal tumor growth inhibition of 67 and 64%, respectively, whereas
      anti-brain-derived neurotrophic factor and anti-NT-4/5 did not inhibit tumor
      growth in this tumor model. Administration of various concentrations (0.1, 1.0,
      or 10.0 microg) of affinity-purified anti-NGF resulted in maximal TSU-Pr1 tumor
      growth inhibition of 49, 62, and 66%, respectively. CONCLUSIONS: These data add
      further support for the therapeutic potential of disrupting trk-signaling events
      in select types of nonneuronal human cancers, specifically prostatic and
      pancreatic carcinomas.

PMID- 12060638
TI  - Synthetic matrix metalloproteinase inhibitors inhibit growth of established
      breast cancer osteolytic lesions and prolong survival in mice.
AB  - PURPOSE: Breast cancer frequently leads to incurable bone metastasis. Essential
      requirements for the development of bone metastasis are cell-cell and cell-matrix
      interactions, release of bioactive growth factors and cytokines, and removal of
      large amounts of bone matrix. Matrix metalloproteinases (MMPs) play an important
      role in all of these processes, but the possibility of using synthetic MMP
      inhibitors to decrease bone metastasis has received little attention.
      EXPERIMENTAL DESIGN: In the present study, we tested two general MMP inhibitors,
      BB-94 and GM6001, in a mouse model of breast cancer-induced bone metastasis.
      RESULTS: In a simulation of intervention therapy, mice were inoculated with
      breast cancer cells, and at the time of diagnosis of osteolytic lesions, the mice
      were treated for 10 or 15 consecutive days with BB-94 or GM6001, respectively.
      Both inhibitors reduced the growth of osteolytic lesions by >55% compared with
      control mice. Next, we simulated prevention therapy by initiating treatment with
      GM6001 at time of inoculation with cancer cells or 3 days earlier. Assessment of
      osteolytic lesions 28 days after inoculation showed that, in both cases, the
      treatment reduced the size of the osteolytic lesions by 60%, compared with that
      of control mice. Importantly, MMP inhibition also resulted in extension of
      symptom-free survival in the mice, whether the treatment was initiated at the
      time of diagnosis of osteolytic lesions or of cancer cell inoculation.
      CONCLUSIONS: The present study suggests the potential of synthetic MMP inhibitors
      as intervention or prevention treatments of breast cancer-induced osteolysis.

PMID- 12060639
TI  - Augmentation of sodium butyrate-induced apoptosis by phosphatidylinositol 3'
      kinase inhibition in the KM20 human colon cancer cell line.
AB  - PURPOSE: We have recently shown that inhibition of the phosphatidylinositol3'
      kinase (PI3k) pathway enhances sodium butyrate (NaBT)-mediated differentiation of
      human colon cancer cells. The purpose of this study was to determine whether PI3k
      inhibition can enhance the inhibitory effect of NaBT on an aggressive human colon
      cancer cell line, KM20. EXPERIMENTAL DESIGN: The KM20 cell line, established from
      a metastatic colon cancer, was treated in vitro with NaBT, gemcitabine, or 5
      fluorouracil either alone or in combination with the PI3k inhibitors wortmannin
      or LY294002; DNA fragmentation and cell viability were measured. As further
      indicators of apoptosis, protein was extracted to determine caspase-9 and caspase
      3 activation and cleavage of poly(ADP-ribose) polymerase. In addition, the effect
      of NaBT and wortmannin on in vivo KM20 tumor growth was determined. RESULTS: We
      demonstrate that inhibition of PI3k enhanced NaBT-mediated apoptosis and
      decreased KM20 cell viability; the nonspecific caspase inhibitor zVAD-fmk blocked
      the induction of apoptosis by the combination treatment. Either wortmannin or
      LY294002, combined with NaBT, enhanced activation of caspase-9 and caspase-3 and
      the subsequent cleavage of poly(ADP-ribose) polymerase. Furthermore, inhibition
      of PI3k increased the sensitivity of KM20 cells to gemcitabine and 5
      fluorouracil. Wortmannin alone inhibited KM20 xenograft growth in vivo; the
      combination of wortmannin and NaBT demonstrated an enhanced effect compared with
      either agent alone. CONCLUSIONS: Our results are the first to show that
      inhibition of PI3k enhances NaBT-mediated colon cancer cell apoptosis through the
      activation of caspase-9 and caspase-3. Moreover, these findings suggest that
      agents that selectively target the PI3k pathway may enhance the effects of
      standard chemotherapeutic agents and provide novel adjuvant treatment for
      selected colon cancers.

PMID- 12060640
TI  - Heterogeneity in interleukin-13 receptor expression and subunit structure in
      squamous cell carcinoma of head and neck: differential sensitivity to chimeric
      fusion proteins comprised of interleukin-13 and a mutated form of Pseudomonas
      exotoxin.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is characterized by a high
      proliferation index and marked propensity for local invasion resulting in poor
      prognosis for these patients. To develop tumor-targeted novel therapeutic agents,
      here we demonstrate that SCCHN cell lines express receptors for an immune
      regulatory cytokine, interleukin (IL) 13. By reverse transcription-PCR (RT-PCR),
      we found that 16 SCCHN cell lines express equally strong RT-PCR positive bands
      for mRNA of IL-13Ralpha1 and IL-4Ralpha chains. However, only three cell lines,
      HN12, YCUM911, and KCCT873, expressed a strong band for transcripts for IL
      13Ralpha2 chain and five cell lines, YCUL891, KCCTC871, KCCL871, KCCTCM901, and
      RPMI 2650 expressed faint bands. Transcripts for IL-2Rgamma(c) chain were absent
      in all of the cell lines tested. Indirect immunofluorescence analysis for four
      different receptor chains confirmed RT-PCR results and showed pronounced
      expression of IL-13Ralpha2 protein in three high IL-13R expressing cell lines.
      All of the cell lines were equally positive for IL-13Ralpha1 and IL-4Ralpha
      chains. Receptor-binding studies demonstrated that IL-13Ralpha2-positive cell
      lines expressed a high density of IL-13 receptors. Using two chimeric proteins
      composed of IL-13 and mutated forms of Pseudomonas exotoxin (IL-13-PE38 or IL-13
      PE38QQR), we found that these two fusion toxins were highly and equally cytotoxic
      to IL-13Ralpha2-positive SCCHN, whereas IL-13Ralpha2-negative cell lines showed
      low or no sensitivity to IL-13 toxins. To additionally substantiate the critical
      role of the IL-13Ralpha2 chain in IL-13R-mediated cytotoxicity, two head and neck
      tumor cell lines (YCUMS861 and KB), devoid of the transcripts of this chain, were
      transfected with IL-13Ralpha2 cDNA and then tested for cytotoxicity. Transient
      transfection of the IL-13Ralpha2 chain highly sensitized these cells to IL-13
      toxin as compared with mock-transfected control cells. Thus, our results indicate
      that IL-13Ralpha2 is present in 50% SCCHN tumor cell lines; of these, 19% are
      high expresser for this chain and respond to IL-13 cytotoxin. Thus, IL-13
      cytotoxin may be a useful agent for high IL-13R-expressing SCCHN.

PMID- 12060641
TI  - The in vitro and in vivo effects of 2-(4-morpholinyl)-8-phenyl-chromone
      (LY294002), a specific inhibitor of phosphatidylinositol 3'-kinase, in human
      colon cancer cells.
AB  - PURPOSE: Phosphatidylinositol 3'-kinase (PI3K) and Akt/protein kinase B(PKB)
      allow for escape from apoptosis in various human cancer cells. We postulated that
      2-(4-morpholinyl)-8-phenyl-chromone (LY294002), a PI3K inhibitor, should
      inactivate Akt/PKB, consequently inhibiting cell proliferation and inducing
      apoptosis in vitro and in vivo. EXPERIMENTAL DESIGN: Human colon cancer cell
      lines (DLD-1, LoVo, HCT15, and Colo205) and their mouse xenografts (DLD-1 and
      LoVo) were used in this study. The expression of phosphorylated Akt (Ser(473))
      and apoptosis in cancer cells were determined by immunoblotting and
      immunohistochemistry. To evaluate the activity of caspase-3 in culturing cells,
      the caspase colorimetric assay was also performed. RESULTS: LY294002 demonstrated
      a remarkable growth-inhibitory and apoptosis-inducing effect in these colon
      cancer cell lines, with decreased expression of phosphorylated Akt (Ser(473)).
      However, there was a great discrepancy between the sensitivity for LY294002 and
      the level of expression of phosphorylated Akt. Although the LoVo and Colo205
      cells exhibited high sensitivity to LY294002 with increased apoptosis, the DLD-1
      and HCT15 cells did not show rapid induction of apoptosis. The caspase-3 activity
      was significantly high in the LoVo cells but not in the DLD-1 cells. In the
      experiments using mouse xenografts, we found that LY294002 administration in vivo
      also resulted in suppression of tumor growth and induction of apoptosis,
      especially in the LoVo tumors, and therefore showed remarkable effectiveness in
      the mouse peritonitis carcinomatosa model. CONCLUSIONS: PI3K-Akt/PKB plays an
      important role in colon cancer development and progression by helping to promote
      cell growth and allowing cells to escape apoptosis. These results propose the
      usefulness of LY294002 as an antitumoral agent for patients with colorectal
      cancer.

PMID- 12060642
TI  - Thalidomide metabolism by the CYP2C subfamily.
AB  - PURPOSE: This research investigated the biotransformation of thalidomide by
      cytochrome P-450 (CYP). EXPERIMENTAL DESIGN: We used liver microsomes from humans
      and/or animals and the recombinant specific CYP isozymes to investigate CYP
      mediated metabolism of thalidomide. RESULTS: Thalidomide was biotransformed into
      5-hydroxythalidomide (5-OH) and diastereomeric 5'-hydroxythalidomide (5'-OH) by
      liver microsomes. The human liver microsomes with higher CYP2C19 activity formed
      more metabolites than those with lower CYP2C19 activity and had less activity in
      metabolite formations than those from rats. Recombinant human CYP2C19 and rat
      CYP2C6 isozymes were primarily responsible for forming these metabolites, and the
      male rat-specific CYP2C11 formed only 5'-OH. 5-OH was subsequently hydroxylated
      to 5,6-dihydroxythalidomide by CYP2C19, CYP2C9, and CYP1A1 in humans and by
      CYP2C11, CYP1A1, CYP2C6, and CYP2C12 in rats. Incubations with S-mephenytoin and
      omeprazole, substrates of CYP2C19, inhibited metabolism by human liver
      microsomes, supporting the involvement of CYP2C19. alpha-Naphthoflavone, an
      inhibitor of CYP1A, simultaneously stimulated the 5-OH formation and inhibited
      cis-5'-OH formation catalyzed by human liver microsomes. The contribution of the
      CYP2C subfamily was supported by the immunoinhibition study using human liver
      microsomes. When we used the microsomes from treated rats, the metabolite
      formations did not increase by inducers for CYP1A, CYP2B, CYP2E, CYP3A, or CYP4A,
      suggesting that these could not be involved in the main metabolic pathway in
      rats. CONCLUSIONS: We discovered that the polymorphic enzyme CYP2C19 is
      responsible for 5- and 5'-hydroxylation of thalidomide in humans. In rats,
      thalidomide was hydroxylated extensively by CYP2C6 as well as the sex-specific
      enzyme CYP2C11.

PMID- 12060643
TI  - Antitumor activity of the novel vascular targeting agent ZD6126 in a panel of
      tumor models.
AB  - PURPOSE: The purpose of this study was to examine the antitumor effects of the
      novel vascular targeting agent ZD6126 and to use histology, CD31
      immunohistochemistry, and electron microscopy to gain an insight into the
      mechanism of action of this novel agent. EXPERIMENTAL DESIGN: The antitumor
      effects of ZD6126 were examined using a range of solid tumor models: (a) ras
      transformed mouse 3T3 fibroblasts (Hras5); and (b) human lung (Calu-6),
      colorectal (LoVo and HT-29), prostate (PC-3), ovarian (SKOV-3), and breast (MDA
      MB-231) tumors, grown as xenografts in nude mice. RESULTS: In vivo, a well
      tolerated dose of ZD6126 was shown to cause rapid effects on tumor endothelium
      leading to exposure of the basal lamina after cell retraction and subsequent loss
      of endothelial cells. This led to thrombosis and vessel occlusion, resulting in
      extensive tumor necrosis 24 h after ZD6126 administration. Dose-response studies
      showed that these effects were seen at a dose 8- to 16-fold lower than the
      maximum tolerated dose, demonstrating that ZD6126 has a wide therapeutic margin
      in these mouse models. A single dose of ZD6126 (200 mg/kg) led to a significant
      growth delay in Calu-6 and LoVo tumors. Growth delay was increased when 100 mg/kg
      ZD6126 was given as a well-tolerated regime in five daily doses. Finally,
      combining ZD6126 with cisplatin resulted in greater than additive enhancement in
      growth delay in the Calu-6 model. CONCLUSIONS: These findings provide direct
      support that ZD6126 selectively disrupts tumor vasculature, demonstrate that it
      has activity in a range of tumor xenograft models, and show that it can
      significantly enhance the antitumor efficacy of cisplatin.

PMID- 12060644
TI  - A preclinical model of minimal residual cancer in the muscle highlights
      challenges associated with adenovirus-mediated p53 gene transfer.
AB  - PURPOSE: Clinical studies have revealed that tumors may recur at the operative
      site if radioresistant p53 mutation-positive residual disease remains in the body
      after treatment. Destruction of these remaining malignant cells, which can be
      present in both mucosal and deep muscle margins, may be achieved using p53
      mediated gene transfer techniques. Most preclinical studies designed to assess
      the feasibility of harnessing this approach have used s.c. tumor models in nude
      mice, but it is anticipated that transduction of tumor cells in the muscle in
      immune-competent hosts may be more difficult. EXPERIMENTAL DESIGN: To address
      this point a new rodent model of residual cancer was established implanting
      PDVC57B tumor cells to create multiple tumor tracts in the muscle of syngeneic
      immune-competent C57Bl/6 mice. s.c. tumors and a s.c. model of residual disease
      were used as comparators. RESULTS: In the s.c. model of residual disease a single
      administration of 5 x 10(10) viral particles of Ad5CMV-p53 suppressed the growth
      of encapsulated tumor at the treatment site in six of six animals, but two of
      these animals had viable nests of tumor outside of the encapsulated zone.
      However, Ad5CMV-p53 had no apparent effect on tumor cell progression in the model
      of residual cancer in the muscle. Creating the muscle model of residual cancer
      with a lower number of cells in the initial inoculum showed that immune-mediated
      effects, as well as those attributable to the transgene, are important in
      preventing tumor outgrowth. The frequency of transduction of tumor cells in the
      muscle, as determined after administration of Ad-beta-galactosidase, was
      typically <3% and markedly different from the 20% transduction observed for the
      s.c. tumor model. CONCLUSIONS: These studies highlight the need to devise
      strategies to improve delivery of adenovirus-mediated gene transfer to nests of
      tumor in muscle before this modality is used to treat residual cancer at this
      site. These may involve approaches such as intravascular delivery, strategies to
      improve vector diffusion, or combination with chemotherapy or radiotherapy to
      enhance gene delivery at these less accessible sites of disease.

PMID- 12060645
TI  - Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen
      on breast and endometrial cancer growth in vivo.
AB  - PURPOSE: Cross-resistance is an important issue for the evaluation of new
      antiestrogens to treat advanced breast cancer patients who have failed tamoxifen
      therapy. In addition, postmenopausal patients treated with long-term adjuvant
      tamoxifen show a 3-4-fold increase in the risk of developing endometrial cancer.
      Consequently, a new second line agent should be more antiestrogenic and less
      estrogen-like on the uterus, and be effective at controlling the growth of breast
      cancer after exposure to tamoxifen. The purpose was to evaluate the effects of
      the new tamoxifen analogue GW5638 on breast and endometrial cancer growth.
      EXPERIMENTAL DESIGN: Athymic mice were transplanted with an endometrial tumor
      model (ECC-1 E2) that is responsive to estrogen and has never been exposed to
      antiestrogen. In addition, we used three breast tumor models: a tamoxifen-naive
      tumor (T47D-E2) and two tamoxifen-stimulated tumors (MT2 TAM and MCF-7 TAM LT).
      The antiestrogen GW5638 (1.5 mg daily), tamoxifen (0.5 mg or 1.5 mg daily), and
      raloxifene (1.5 mg daily) were given p.o. The pure antiestrogen ICI182,780 (5 mg
      once a week) was given s.c. Western blots from MCF-7 TAM breast tumors were
      performed to demonstrate the regulation of estrogen receptor alpha expression by
      different ligands. RESULTS: Estradiol and GW5638 down-regulated the receptor
      compared with control. ICI182,780 completely degraded the receptor but tamoxifen
      had no effect. GW5638 did not promote tumor growth, and was effective in blocking
      the effects of postmenopausal estradiol on the growth of tamoxifen-naive breast
      and endometrial tumors. However, raloxifene did not completely block the effects
      of postmenopausal estradiol on the growth of tamoxifen-naive endometrial tumor
      after 14 weeks. GW5638 and ICI182,780 but not raloxifene were also effective in
      blocking the tamoxifen-stimulated breast tumor growth in athymic mice.
      CONCLUSIONS: GW5638 is more effective than raloxifene in blocking the effect of
      estrogen on tamoxifen-naive endometrial cancer. More importantly, GW5638, like
      the pure antiestrogen ICI182,780, is able to block the growth of breast cancer
      stimulated by tamoxifen differently from raloxifene. GW5638 down-regulates
      estrogen receptor but does not completely destroy the receptor. Therefore, based
      on our findings, GW5638 could be developed as a second line agent for advanced
      breast cancer patients and an important first line agent to evaluate as an
      adjuvant treatment or chemopreventive.

PMID- 12060646
TI  - Establishment and characterization of acquired resistance to the farnesyl protein
      transferase inhibitor R115777 in a human colon cancer cell line.
AB  - R115777 (Zarnestra) is a farnesyl protein transferase inhibitor currently
      undergoing worldwide clinical trials. As acquired drug resistance may limit the
      efficacy of the drug, a model of acquired resistance has been established in
      vitro by continuous drug exposure of the human colon cancer cell line KM12. A
      stably resistant cell line possessing 13-fold resistance to R115777 was
      generated. The resistant cells showed cross-resistance to another, structurally
      different farnesyl transferase inhibitor-277, but not to GGTI-298. A lack of
      cross-resistance was observed to a variety of other agents, which included
      clinically used drugs, such as doxorubicin, etoposide, cisplatin, and paclitaxel,
      as well as signal transduction blockers, such as the mitogen-activated
      protein/extracellular signal-regulated kinase kinase inhibitor UO126, the
      phosphatidylinositol 3'-kinase inhibitor LY294002, and the epidermal growth
      factor receptor tyrosine kinase inhibitor PD153035. Resistance did not appear to
      be related to differences in drug efflux pumps, such as P-glycoprotein or in drug
      accumulation. Total levels of farnesyl transferase protein subunits were similar
      in the parent and resistant cells, but, notably, the enzyme activity was markedly
      reduced in the resistant cell line compared with the parent cells. This was not
      because of a mutation in the enzyme or a difference in activation of the alpha
      subunit of farnesyl transferase by phosphorylation. Hence, resistance to R115777
      was generated; the mechanism of resistance in this model may be associated with
      the enzyme target of the inhibitor. The results suggest that the development of
      clinical resistance may occur with farnesyl protein transferase inhibitors.

PMID- 12060647
TI  - Observation of molecular changes of a necrotic tissue from a murine carcinoma by
      Fourier-transform infrared microspectroscopy.
AB  - PURPOSE: Our purpose is to develop infrared (IR) microspectroscopy as a new
      optical diagnostic tool to support conventional lightscopic techniques in
      investigating the viability of carcinoma tissues and to develop its use in the
      evaluation of the early effects of anticancer therapy by monitoring the IR
      spectra in the necrotic area. EXPERIMENTAL DESIGN: We evaluated the tissue which
      amassed for 4 weeks after the isotransplantation of mouse squamous cell carcinoma
      into the thigh of mice. The borders of the necrotic area of frozen tissue
      specimens were investigated by Fourier-transform IR microspectroscopy and
      conventional histological staining. RESULTS: A significantly higher accumulation
      of cholesterol was observed in the necrotic tissue of a carcinoma. The mechanism
      of this phenomenon is hitherto unrecognized. We proposed that the accumulated
      cholesterol may lie extracellularly as a result of the ruptured plasma and
      internal membranes after the swelling of the necrotic cells brought on by
      hypoxia. The analysis of the secondary structure of protein revealed that the
      amounts of beta-sheet increased significantly in striking contrast to the
      decreasing amounts of alpha-helix in a necrotic area of a carcinoma. It is
      plausible that this structural conversion of protein was because of lipid
      autooxidation products, such as cholesterol oxide but not cholesterol itself,
      which possesses cell toxicity and could be generated in a necrotic area.
      CONCLUSIONS: We conclude that it will be possible to evaluate the efficacy of the
      clinical treatment of carcinoma by monitoring subtle biological changes of
      cholesterol absorbance in the early stage of necrosis because of anticancer
      treatment.

PMID- 12060648
TI  - Correspondence re: B. Molnar et al., Circulating tumor cell clusters in the
      peripheral blood of colorectal cancer patients. Clin. Cancer Res., 7: 4080-4085,
      2001.

PMID- 12060650
TI  - Phosphorylation of histone h3 at serine 10 cannot account directly for the
      detachment of human heterochromatin protein 1gamma from mitotic chromosomes in
      plant cells.
AB  - Heterochromatin protein 1 (HP1) controls heterochromatin formation in animal
      cells, at least partly through interaction with lysine 9 (Lys-9)-methylated
      histone H3. We aimed to determine whether a structurally conserved human HP1
      protein exhibits conserved heterochromatin localization in plant cells and
      studied its relation to modified histone H3. We generated transgenic tobacco
      plants and cycling cells expressing the human HP1gamma fused to green fluorescent
      protein (GFP) and followed its association with chromatin. Plants expressing GFP
      HP1gamma showed no phenotypic perturbations. We found that GFP-HP1gamma is
      preferentially associated with the transcriptionally "inactive" heterochromatin
      fraction, a fraction enriched in Lys-9-methylated histone H3. During mitosis GFP
      HP1gamma is detached from chromosomes concomitantly with phosphorylation of
      histone H3 at serine 10 and reassembles as cells exit mitosis. However, this
      phosphorylation cannot directly account for the dissociation of GFP-HP1gamma from
      mitotic chromosomes inasmuch as phosphorylation does not interfere with binding
      to HP1gamma. It is, therefore, possible that phosphorylation at serine 10 creates
      a "code" that is read by as yet an unknown factor(s), eventually leading to
      detachment of GFP-HP1gamma from mitotic chromosomes. Together, our results
      suggest that chromatin organization in plants and animals is conserved, being
      controlled at least partly by the association of HP1 proteins with methylated
      histone H3.

PMID- 12060652
TI  - The double-stranded RNA-activated kinase, PKR, can phosphorylate hepatitis D
      virus small delta antigen at functional serine and threonine residues.
AB  - Hepatitis D virus (HDV) encodes two proteins, the 24-kDa small delta antigen (S
      HDAg) and 27-kDa large delta antigen (L-HDAg) in its single open reading frame.
      Both of them had been identified as nuclear phosphoproteins. Moreover, the
      phosphorylated form of S-HDAg was shown to be important for HDV replication.
      However, the kinase responsible for S-HDAg phosphorylation remains unknown.
      Therefore, we employed an in-gel kinase assay to search candidate kinases and
      indeed identified a kinase with a molecular mass of about 68 kDa. Much evidence
      demonstrated this kinase to be the double-stranded RNA-activated kinase, PKR. The
      immunoprecipitated endogenous PKR was sufficient to catalyze S-HDAg
      phosphorylation, and the kinase activity disappeared in the PKR-depleted cell
      lysate. The S-HDAg and PKR could be co-immunoprecipitated together, and both of
      them co-located in the nucleolus. The LC/MS/MS analysis revealed that the serine
      177, serine 180, and threonine 182 of S-HDAg were phosphorylated by PKR in vitro.
      This result was consistent with previous phosphoamino acid analysis indicating
      that serine and threonine were phosphorylation targets in S-HDAg. Furthermore,
      serine 177 was also shown to be the predominant phosphorylation site for S-HDAg
      purified the from cell line. In dominant negative PKR-transfected cells, the
      level of phosphorylated S-HDAg was suppressed, but replication of HDV was
      enhanced. Other than human immunodeficiency virus type 1 trans-activating protein
      (Tat), S-HDAg is another viral protein phosphorylated by PKR that may regulates
      HDV replication and viral response to interferon therapy.

PMID- 12060651
TI  - Prolactin induces SHP-2 association with Stat5, nuclear translocation, and
      binding to the beta-casein gene promoter in mammary cells.
AB  - The Src homology 2 (SH2) domain containing protein-tyrosine phosphatase SHP-2
      contributes to prolactin receptor (PRLR) signal transduction to beta-casein gene
      promoter activation. We report for the first time that SHP-2 physically
      associates with the signal transducer and activator of transcription-5a (Stat5a),
      an important mediator of PRLR signaling to milk protein gene activation, in the
      mouse mammary HC11 and the human breast cancer T47D cells when stimulated with
      prolactin (PRL) and human growth hormone, respectively. In addition,
      overexpression studies indicate that the carboxyl-terminal SH2 domain of SHP-2 is
      required to maintain tyrosine phosphorylation of Stat5 and its interaction with
      SHP-2. Furthermore, we demonstrate by nuclear co-immunoprecipitation and indirect
      immunofluorescence studies that PRL stimulation of mammary cells leads to the
      nuclear translocation of SHP-2 as a complex with Stat5a. This process was found
      to involve the catalytic activity of the phosphatase. Finally, using the Stat5
      GAS (gamma-activated sequence) element of the beta-casein gene promoter in
      electrophoretic mobility shift assays, we demonstrate that PRL induces the SHP-2
      Stat5a complex to bind to DNA. The presence of the phosphatase in the protein
      bound DNA complex was verified by using polyclonal antisera to SHP-2. Our studies
      indicate a tight physical and functional interaction between SHP2 and Stat5
      required for regulation and perpetuation of PRL-mediated signaling in mammary
      cells and suggest a potential role for SHP-2 in the nucleus.

PMID- 12060653
TI  - Two mcm3 mutations affect different steps in the initiation of DNA replication.
AB  - Mcm3 is a subunit of the hexameric MCM2-7 complex required for the initiation and
      elongation of DNA replication in eukaryotes. We have characterized two mutant
      alleles, mcm3-1 and mcm3-10, in Saccharomyces cerevisiae and showed that they are
      defective at different steps of the replication initiation process. Mcm3-10
      contains a P118L substitution that compromises its interaction with Mcm5 and the
      recruitment of Mcm3 and Mcm7 to a replication origin. P118 is conserved between
      Mcm3, Mcm4, Mcm5, and Mcm7. An identical substitution of this conserved residue
      in Mcm5 (P83L of mcm5-bob1) strengthens the interaction between Mcm3 and Mcm5 and
      allows cells to enter S phase independent of Cdc7-Dbf4 kinase (Hardy, C. F.,
      Dryga, O., Pahl, P. M. B., and Sclafani, R. A. (1997) Proc. Natl. Acad. Sci. U.
      S. A. 94, 3151-3155). Mcm3-1 contains a G246E mutation that diminishes the
      efficiency of replication initiation (Yan, H., Merchant, A. M., and Tye, B. K.
      (1993) Genes Dev. 7, 2149-2160) but not its interaction with Mcm5 or recruitment
      of the MCM2-7 complex to replication origin. These observations indicate that
      Mcm3-10 is defective in a step before, and Mcm3-1 is defective in a step after
      the recruitment of the MCM2-7 complex to replication origins.

PMID- 12060654
TI  - Human neutrophils use the myeloperoxidase-hydrogen peroxide-chloride system to
      chlorinate but not nitrate bacterial proteins during phagocytosis.
AB  - The generation of extracellular oxidants by neutrophils has been widely
      investigated, but knowledge about the chemical reactions that occur in the
      phagolysosome, the cellular compartment that kills pathogens, is more limited.
      One important pathway may involve the production of potent halogenating agents
      such as hypochlorous acid (HOCl) by the myeloperoxidase-hydrogen peroxide-halide
      system. However, explorations of the oxidation chemistry of phagolysosomes have
      been hampered by the organelle's inaccessibility. To overcome this limitation, we
      recovered Escherichia coli that had been internalized by human neutrophils. We
      then analyzed the bacterial proteins for 3-chlorotyrosine, a stable marker of
      damage by HOCl. Mass spectrometric analysis revealed that levels of 3
      chlorotyrosine in E. coli proteins increased markedly after the bacteria were
      internalized by human neutrophils. This increase failed to occur in E. coli
      exposed to neutrophils deficient in NADPH oxidase or myeloperoxidase, implicating
      H(2)O(2) and myeloperoxidase in the halogenation reaction. The extent of protein
      chlorination by normal neutrophils paralleled bacterial killing. Our observations
      support the view that the phagolysosome of human neutrophils uses the
      myeloperoxidase-hydrogen peroxide-chloride system to chlorinate bacterial
      proteins. In striking contrast, human neutrophils failed to nitrate bacterial
      proteins unless the medium was supplemented with 1 mm nitrite, and the level of
      nitration was low. Protein chlorination associated with bacterial killing was
      unaffected by the presence of nitrite in the medium. Nitration required NADPH
      oxidase but appeared to be independent of myeloperoxidase, suggesting that
      neutrophils can nitrate proteins through a pathway that requires nitrite but is
      independent of myeloperoxidase.

PMID- 12060655
TI  - Specific cleavage of hepatitis C virus RNA genome by human RNase P.
AB  - We have found that RNase P from HeLa cells specifically and efficiently cleaves
      hepatitis C virus (HCV) transcripts in vitro. The evidence includes
      identification of the 5'-phosphate polarity of the newly generated termini at
      position A(2860) as well as immunological and biochemical assays. Active cleavage
      has been shown in five dominant sequences of HCV "quasispecies" differing at or
      near the position of cleavage, demonstrating that this is a general property of
      HCV RNA. During the analysis, a second cleavage event was found in the 3' domain
      of the internal ribosome entry site. We have found that HCV RNA competitively
      inhibits pre-tRNA cleavage by RNase P, suggesting that HCV RNA has structural
      similarities to tRNA. This finding sets HCV apart from other pathogens causing
      serious human diseases and represents the first description of human RNase P
      viral RNA cleavage. Here we discuss the possible meaning of these RNase P
      accessible structures built into the viral genome and their possible role in
      vivo. Moreover, such structures within the viral genome might be vulnerable to
      attack by therapeutic strategies.

PMID- 12060656
TI  - Distinct sets of adjacent heterogeneous nuclear ribonucleoprotein (hnRNP) A1/A2
      binding sites control 5' splice site selection in the hnRNP A1 mRNA precursor.
AB  - In the heterogeneous nuclear ribonucleoprotein (hnRNP) A1 pre-mRNA, different
      regions in the introns flanking alternative exon 7B have been implicated in the
      production of the A1 and A1B mRNA splice isoforms. Among these, the CE1a and CE4
      elements, located downstream of common exon 7 and alternative exon 7B,
      respectively, are bound by hnRNP A1 to promote skipping of exon 7B in vivo and
      distal 5' splice site selection in vitro. Here, we report that CE1a is flanked by
      an additional high affinity A1 binding site (CE1d). In a manner similar to CE1a,
      CE1d affects 5' splice site selection in vitro. Consistent with a role for hnRNP
      A1 in the activity of CE1d, a mutation that abrogates A1 binding abolishes distal
      5' splice site activation. Moreover, the ability of CE1d to stimulate distal 5'
      splice site usage is lost in an HeLa extract depleted of hnRNP A/B proteins, and
      the addition of recombinant A1 restores the activity of CE1d. Notably, distal 5'
      splice site selection mediated by A1 binding sites is not compromised in an
      extract prepared from mouse cells that are severely deficient in hnRNP A1
      proteins. In this case, we show that hnRNP A2 compensates for the A1 deficiency.
      Further studies with the CE4 element reveal that it also consists of two distinct
      portions (CE4m and CE4p), each one capable of promoting distal 5' splice site use
      in an hnRNP A1-dependent manner. The presence of multiple A1/A2 binding sites
      downstream of common exon 7 and alternative exon 7B probably plays an important
      role in maximizing the activity of hnRNP A1/A2 proteins.

PMID- 12060657
TI  - Structure of the regulatory N-domain of human cardiac troponin C in complex with
      human cardiac troponin I147-163 and bepridil.
AB  - Cardiac troponin C (cTnC) is the Ca(2+)-dependent switch for contraction in heart
      muscle and a potential target for drugs in the therapy of heart failure. Ca(2+)
      binding to the regulatory domain of cTnC (cNTnC) induces little structural change
      but sets the stage for cTnI binding. A large "closed" to "open" conformational
      transition occurs in the regulatory domain upon binding cTnI(147-163) or
      bepridil. This raises the question of whether cTnI(147-163) and bepridil compete
      for cNTnC.Ca(2+). In this work, we used two-dimensional (1)H,(15)N-heteronuclear
      single quantum coherence (HSQC) NMR spectroscopy to examine the binding of
      bepridil to cNTnC.Ca(2+) in the absence and presence of cTnI(147-163) and of
      cTnI(147-163) to cNTnC.Ca(2+) in the absence and presence of bepridil. The
      results show that bepridil and cTnI(147-163) bind cNTnC.Ca(2+) simultaneously but
      with negative cooperativity. The affinity of cTnI(147-163) for cNTnC.Ca(2+) is
      reduced approximately 3.5-fold by bepridil and vice versa. Using multinuclear and
      multidimensional NMR spectroscopy, we have determined the structure of the
      cNTnC.Ca(2+).cTnI(147-163).bepridil ternary complex. The structure reveals a
      binding site for cTnI(147-163) primarily located on the A/B interhelical
      interface and a binding site for bepridil in the hydrophobic pocket of
      cNTnC.Ca(2+). In the structure, the N terminus of the peptide clashes with part
      of the bepridil molecule, which explains the negative cooperativity between
      cTnI(147-163) and bepridil for cNTnC.Ca(2+). This structure provides insights
      into the features that are important for the design of cTnC-specific cardiotonic
      drugs, which may be used to modulate the Ca(2+) sensitivity of the myofilaments
      in heart muscle contraction.

PMID- 12060658
TI  - A second UDP-glucose pyrophosphorylase is required for differentiation and
      development in Dictyostelium discoideum.
AB  - Uridine diphosphoglucose pyrophosphorylase (UDPGP) is a developmentally regulated
      enzyme in Dictyostelium discoideum, which is involved in trehalose, cellulose,
      and glycogen synthesis. Two independent UDPGP proteins are believed to be
      responsible for this activity. To determine the relative contributions of each
      protein, the genes encoding them were disrupted individually. Cells lacking the
      udpgp1 gene exhibit normal growth and development and make normal levels of
      cellulose. In agreement with these phenotypes, udpgp1(-) cells still have UDPGP
      activity, although at a reduced level. This supports the importance of the second
      UDPGP gene. This newly identified gene, ugpB, encodes an active UDPGP as
      determined by complementation in Escherichia coli. When this gene is disrupted,
      cells undergo aberrant differentiation and development ending with small, gnarled
      fruiting bodies. These cells also have decreased spore viability and decreased
      levels of glycogen, whose production requires UDPGP activity. These phenotypes
      suggest that UgpB constitutes the major UDPGP activity produced during
      development. Sequence analysis of the two UDPGP genes shows that UgpB has higher
      homology to other eukaryotic UDPGPs than does UDPGP1. This includes the presence
      of 5 conserved lysine residues. Udpgp1 only has 1 of these lysines.

PMID- 12060659
TI  - RhoA-mediated Ca2+ sensitization in erectile function.
AB  - A Rho-kinase inhibitor increases corpus cavernosum (CC) pressure in an in vivo
      rat model (Chitaley, K., Wingard, C. J., Webb, R. C., Branam, H., Stopper, V. S.,
      Lewis, R. W., and Mills, T. M. (2001) Nat. Med. 7, 119-122) suggesting that Rho
      mediated Ca(2+) sensitization of CC smooth muscle maintains the flaccid
      (contracted) state. We directly demonstrate Ca(2+) sensitization of permeabilized
      rabbit and human CC and identify a highly expressed molecular component of this
      pathway. Ca(2+) sensitization of force induced by endothelin or GTPgammaS was
      significantly greater in CC than in rabbit ileum smooth muscle and was
      accompanied by a 17-fold higher RhoA content. Pull-down assays with the RhoA
      binding domain of mDia showed the high RhoA content of CC to be available for
      activation by GTPgammaS. Ca(2+) sensitization induced by endothelin,
      phenylephrine, or GTPgammaS was completely relaxed by the Rho kinase inhibitor Y
      27632. Human and rabbit CC both express the phosphatase inhibitor CPI-17, the
      myosin phosphatase regulatory (MYPT-1) and catalytic (PP1delta) subunits, and two
      isoforms of Rho kinase. We suggest that high expression of RhoA contributes,
      through RhoA-mediated Ca(2+) sensitization, to the flaccid state of CC that can
      be reversed by a water-soluble, orally active Rho kinase inhibitor suitable for
      therapy of erectile dysfunction.

PMID- 12060660
TI  - Role of the N-terminal transmembrane region of the multidrug resistance protein
      MRP2 in routing to the apical membrane in MDCKII cells.
AB  - In polarized cells, the multidrug resistance protein MRP2 is localized in the
      apical plasma membrane, whereas MRP1, another multidrug resistance protein (MRP)
      family member, is localized in the basolateral membrane. MRP1 and MRP2 are
      thought to contain an N-terminal region of five transmembrane segments (TMD(0))
      coupled to 2 times six transmembrane segments via an intracellular loop (L(0)).
      We previously demonstrated for MRP1 that a mutant lacking TMD(0) but still
      containing L(0), called L(0)DeltaMRP1, was functional and routed to the lateral
      plasma membrane. To investigate the role of the TMD(0)L(0) region of MRP2 in
      routing to the apical membrane, we generated mutants similar to those made for
      MRP1. In contrast to L(0)DeltaMRP1, L(0)DeltaMRP2 was associated with an
      intracellular compartment, most likely endosomes. Co-expression with TMD(0),
      however, resulted in apical localization of L(0)DeltaMRP2 and transport activity.
      Uptake experiments with vesicles containing L(0)DeltaMRP2 demonstrated that the
      molecule is able to transport LTC(4). An MRP2 mutant without TMD(0)L(0),
      DeltaMRP2, was only core-glycosylated and localized intracellularly. Co
      expression of DeltaMRP2 with TMD(0)L(0) resulted in an increased protein level of
      DeltaMRP2, full glycosylation of the protein, routing to the apical membrane, and
      transport activity. Our results suggest that the TMD(0) region is required for
      routing to or stable association with the apical membrane.

PMID- 12060661
TI  - Activation of p38 alpha MAPK enhances collagenase-1 (matrix metalloproteinase
      (MMP)-1) and stromelysin-1 (MMP-3) expression by mRNA stabilization.
AB  - Here, we have examined the role of distinct MAPK pathways in the regulation of
      collagenase-1 (matrix metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3)
      expression by human skin fibroblasts. Tumor necrosis factor-alpha rapidly and
      transiently activated ERK1/2 and JNK in fibroblasts, whereas the activation of
      p38 MAPK was more persistent. Inhibition of p38 activity by SB203580 markedly (by
      80-90%) inhibited induction of MMP-1 and MMP-3 expression by tumor necrosis
      factor-alpha, whereas blocking the activation of ERK1/2 by PD98059 had no effect.
      Activation of endogenous ERK1/2 by adenovirus-mediated transfer of constitutively
      active MEK1 resulted in potent induction of MMP-1 and MMP-3 expression.
      Activation of endogenous or adenovirally expressed p38 alpha by adenovirally
      delivered constitutively active MKK3b and MKK6b also enhanced MMP-1 and MMP-3
      expression and augmented the up-regulatory effect of ERK1/2 activation on the
      expression of these MMPs. Activation of ERK1/2 resulted in induction of c-jun,
      junB, and c-fos expression, whereas activation of p38 alone had no effect. In
      contrast, activation of p38 alpha resulted in marked stabilization of MMP-1 and
      MMP-3 mRNAs. These results identify two distinct and complementary signaling
      mechanisms mediating induction of MMP-1 and MMP-3 expression in dermal
      fibroblasts: AP-1-dependent transcriptional activation via the ERK1/2 pathway and
      AP-1-independent enhancement via p38 alpha MAPK by mRNA stabilization. It is
      conceivable that both modes of action play an important role in controlling the
      proteolytic phenotype of fibroblasts, e.g. in wound repair and tumor invasion.

PMID- 12060662
TI  - Characterization and functional analysis of the siderophore-iron transporter
      CaArn1p in Candida albicans.
AB  - Siderophores are small organic compounds with high affinity for ferric iron.
      Microorganisms commonly acquire iron via siderophore secretion and uptake. Here
      we report the characterization of the siderophore transporter CaArn1p in the
      fungal pathogen Candida albicans. Deletion of CaARN1 reduced the ability of C.
      albicans to use iron bound to the hydroxamate-type siderophore ferrichrome and
      abolished it when two high-affinity iron permease genes (CaFTR1 and CaFTR2) were
      also deleted, indicating a role of CaArn1p as well as the permeases in
      ferrichrome-iron uptake. Caarn1Delta (but not Caftr1DeltaCaftr2Delta) assimilated
      iron from another hydroxamate-type siderophore, ferrioxamine B, suggesting that
      iron uptake from this compound depends on the permeases, but not on CaArn1p.
      Northern blot analysis revealed that the transcription repressor CaTup1p
      repressed CaARN1 expression under iron-replete conditions via the DNA-binding
      protein Rfg1p. Green fluorescent protein-tagged CaArn1p was observed
      predominantly in the plasma membrane, with some in the cytoplasm as distinct
      spots. The number of these spots increased with the increase in ferrichrome
      concentration, suggesting that CaArn1p internalization might be a mechanism for
      ferrichrome-iron uptake or for recycling the transporter. Caarn1Delta did not
      show reduced virulence when injected into the blood stream of mice, implying that
      CaArn1p is not required for iron uptake along this route of infection.

PMID- 12060663
TI  - Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein
      Cdx2 interact functionally to modulate intestinal gene transcription. Implication
      for the developmental regulation of the sucrase-isomaltase gene.
AB  - Sucrase-isomaltase (SI), an intestine-specific gene, is induced in the
      differentiated small intestinal villous epithelium during the suckling-weaning
      transition in mice. We have previously identified cis-acting elements within a
      short evolutionarily conserved SI promoter. However, the nature and profile of
      expression of the interacting proteins have not been fully characterized during
      this developmental transition. Herein, we show that hepatocyte nuclear factor-1
      alpha (HNF-1 alpha), GATA-4, and caudal related homeodomain proteins Cdx2 and
      Cdx1 are the primary transcription factors from the adult mouse intestinal
      epithelium to interact with the SIF3, GATA, and SIF1 elements of the SI promoter.
      We wanted to study whether HNF-1 alpha, GATA-4, and Cdx2 can cooperate in the
      regulation of SI gene expression. Immunolocalization experiments revealed that
      HNF-1 alpha is detected in rare epithelial cells of suckling mice and becomes
      progressively more expressed in the villous epithelial cells during the suckling
      weaning transition. GATA-4 protein is expressed exclusively in villous
      differentiated epithelial cells of the proximal small intestine, decreases in
      expression in the ileum, and becomes undetectable in the colon. HNF-1 alpha, GATA
      4, and Cdx2 interact in vitro and in vivo. These factors activate SI promoter
      activity in cotransfection experiments where GATA-4 requires the presence of both
      HNF-1 alpha and Cdx2. These findings imply a combinatory role of HNF-1 alpha,
      Cdx2, and GATA-4 for the time- and position-dependent regulation of SI
      transcription during development.

PMID- 12060664
TI  - Reconstitution of nucleosome positioning, remodeling, histone acetylation, and
      transcriptional activation on the PHO5 promoter.
AB  - The PHO5 gene promoter is an important model for the study of gene regulation in
      the context of chromatin. Upon PHO5 activation the chromatin structure is
      reconfigured, but the mechanism of this transition remains unclear. Using
      templates reconstituted into chromatin with purified recombinant yeast core
      histones, we have investigated the mechanism of chromatin structure
      reconfiguration on the PHO5 promoter, a prerequisite for transcriptional
      activation. Footprinting analyses show that intrinsic properties of the promoter
      DNA are sufficient for translational nucleosome positioning, which approximates
      that seen in vivo. We have found that both Pho4p and Pho2p can bind their cognate
      sites on chromatin-assembled templates without the aid of histone-modifying or
      nucleosome-remodeling factors. However, nucleosome remodeling by these
      transcriptional activators requires an ATP-dependent activity in a yeast nuclear
      extract fraction. Finally, transcriptional activation on chromatin templates
      requires acetyl-CoA in addition to these other activities and cofactors. The
      addition of acetyl-CoA results in significant core histone acetylation. These
      findings indicate that transcriptional activation requires Pho4p, Pho2p,
      nucleosome remodeling, and nucleosome acetylation. Furthermore, we find that DNA
      binding, nucleosome remodeling, and transcriptional activation are separable
      steps, facilitating biochemical analysis of the PHO5 regulatory mechanism.

PMID- 12060665
TI  - Ectopic expression of protein-tyrosine kinase Bcr-Abl suppresses tumor necrosis
      factor (TNF)-induced NF-kappa B activation and IkappaBalpha phosphorylation.
      Relationship with down-regulation of TNF receptors.
AB  - Bcr-Abl, the product of the protooncogene bcr-abl, is a constitutively active
      protein-tyrosine kinase that is highly expressed in chronic myelogenous leukemia
      and in acute myeloid leukemia cells. Because Bcr-Abl is known to provide
      mitogenic signals through suppression of apoptosis, we investigated the effect of
      this oncogene product on signaling by tumor necrosis factor (TNF), a proapoptotic
      cytokine. We used a bcr-abl-deficient human megakaryocytic leukemia cell line
      MO7E and an isogenic MBA cell line stably transfected with bcr-abl.
      Electrophoretic mobility shift assay revealed that TNF activated the nuclear
      transcription factor NF-kappaB in MO7E cells but not in MBA cells. The impaired
      NF-kappaB activation in Bcr-Abl-expressing cells was not due to absence of the NF
      kappaB proteins p65, p50, or p100 or of IkappaBalpha or IkappaBbeta. Okadaic acid
      induced NF-kappaB activation was unaffected by Bcr-Abl expression. TNF induced
      IkappaBalpha phosphorylation and degradation in MO7E cells but not in MBA cells.
      The suppression of TNF-induced NF-kappaB activation by Bcr-Abl was not restricted
      to MBA cells, because ectopic expression of Bcr-Abl in human acute myeloid
      leukemia HL-60 cells also blocked TNF-induced NF-kappaB activation. When examined
      for the TNF receptors by the radioreceptor assay, flow cytometry, or Western blot
      analysis, we found that Bcr-Abl expression down-regulated the expression of the
      TNF receptors. The RNase protection assay and Northern blot analysis revealed the
      transcriptional down-regulation of the TNF receptor by Bcr-Abl protein. Overall,
      these results indicate that ectopic expression of Bcr-Abl interferes with the TNF
      signaling pathway through the down-regulation of TNF receptors.

PMID- 12060666
TI  - The nuclear receptor interaction domain of GRIP1 is modulated by covalent
      attachment of SUMO-1.
AB  - The steroid receptor coactivator (SRC) proteins comprise a well-characterized
      family of nuclear receptor (NR) coactivators that increase transcriptional
      activation by NRs via covalent modification of chromatin proteins and recruitment
      of other coactivators. We have recently shown that the SRC family member GRIP1
      interacts with a class of SUMO-1 (small ubiquitin-like modifier 1) E3 ligases,
      the PIAS proteins, and that the coactivator is subjected to SUMO-1 modifications
      (sumoylation). In this work, we demonstrate that lysine residues 239, 731, and
      788 of GRIP1 serve as principal attachment sites for SUMO-1. Lys-731 and Lys-788
      are located in the NR interaction domain (NID), and their substitution by
      arginines impairs the ability of GRIP1 to colocalize with androgen receptor (AR)
      in nuclei. Likewise, Lys-731 and Lys-788 mutants of GRIP1 have attenuated ability
      to enhance AR-dependent transcription and fail to synergize with PIASx beta
      mediated activation of AR function, indicating that sumoylation modifies the
      ability of GRIP1 to function as a steroid receptor coactivator. The Lys-731
      sumoylation site is conserved in SRC-3 and SRC-1, and the NIDs of the latter
      coactivators harbor one or two additional sites matching with the consensus sites
      for SUMO-1 attachment, respectively, suggesting a more general role for the
      modification in the regulation of SRC protein activity.

PMID- 12060667
TI  - The cockayne syndrome group B gene product is involved in cellular repair of 8
      hydroxyadenine in DNA.
AB  - Cockayne syndrome (CS) is a human disease characterized by sensitivity to
      sunlight, severe neurological abnormalities, and accelerated aging. CS has two
      complementation groups, CS-A and CS-B. The CSB gene encodes the CSB protein with
      1493 amino acids. We previously reported that the CSB protein is involved in
      cellular repair of 8-hydroxyguanine, an abundant lesion in oxidatively damaged
      DNA and that the putative helicase motif V/VI of the CSB may play a role in this
      process. The present study investigated the role of the CSB protein in cellular
      repair of 8-hydroxyadenine (8-OH-Ade), another abundant lesion in oxidatively
      damaged DNA. Extracts of CS-B-null cells and mutant cells with site-directed
      mutation in the motif VI of the putative helicase domain incised 8-hydroxyadenine
      in vitro less efficiently than wild type cells. Furthermore, CS-B-null and motif
      VI mutant cells accumulated more 8-hydroxyadenine in their genomic DNA than wild
      type cells after exposure to gamma-radiation at doses of 2 or 5 Gy. These results
      suggest that the CSB protein contributes to cellular repair of 8-OH-Ade and that
      the motif VI of the putative helicase domain of CSB is required for this
      activity.

PMID- 12060668
TI  - Purification and characterization of a cyclooxygenase-2 and angiogenesis
      suppressing factor produced by human fibroblasts.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays an important role in
      several pathophysiological processes, including inflammation, angiogenesis, and
      tumorigenesis. We have recently observed that COX-2 induction is restrained in
      proliferating fibroblasts. The mechanism by which this occurs is unclear. Here,
      we report the detection and isolation from the conditioned medium of
      proliferating fibroblasts a factor that suppressed COX-2 expression. This factor,
      which was named cytoguardin, suppressed COX-2 protein levels induced by phorbol
      12-myristate 13-acetate, interleukin-1beta, tumor necrosis factor alpha, and
      lipopolysaccharide (LPS) in fibroblasts and LPS-induced COX-2 protein levels and
      promoter activities in human endothelial cells and murine RAW 264.7 cells in a
      comparable concentration-dependent manner. It inhibited COX-2 expression induced
      by angiogenic factors and endothelial tube formation induced by angiogenic
      factors and colon cancer cell medium. These findings provide evidence for the
      control of COX-2 transcription by an endogenous cellular factor.

PMID- 12060669
TI  - The Src-cortactin pathway is required for clustering of E-selectin and ICAM-1 in
      endothelial cells.
AB  - Adhesion molecules such as E-selectin and intercellular adhesion molecule-1 (ICAM
      1) expressed on endothelial cells (ECs) at sites of inflammation play an
      important role in the recruitment of leukocytes from the bloodstream into
      extravascular tissue. However, little is known about the signaling pathways that
      are initiated in ECs following adhesion molecule engagement. Here, we report that
      an 85-kDa protein becomes tyrosine phosphorylated in human ECs following
      leukocyte adhesion or upon antibody-induced clustering of E-selectin or ICAM-1.
      Through immunoprecipitation experiments, this protein was identified as
      cortactin, a cytoskeleton-binding molecule and prominent src substrate involved
      in cell adhesion. Following adhesion molecule clustering, cortactin
      phosphorylation was inhibited by the src family kinase inhibitor PP2. Both src
      and tyrosine-phosphorylated cortactin were found to be associated with E-selectin
      and ICAM-1 following adhesion of antibody-coated beads to ECs. PP2 did not
      inhibit the association of cortactin with E-selectin and ICAM-1; however, PP2
      inhibited adhesion between paraformaldehyde-fixed THP-1 cells and ECs. This
      decrease in adhesion correlated with inhibition of adhesion molecule clustering
      on PP2-treated ECs at sites of THP-1 attachment. These findings implicate src and
      cortactin as mediators of leukocyte/EC interactions at sites of inflammation by
      regulating adhesion molecule clustering on ECs.

PMID- 12060670
TI  - The transcription factor Prox1 is a marker for lymphatic endothelial cells in
      normal and diseased human tissues.
AB  - Detection of lymphatic endothelal cells (LECs) has been problematic because of
      the lack of specific markers. The homeobox transcription factor Prox1 is
      expressed in LECs of murine and avian embryos. We have studied expression of
      Prox1 in human tissues with immunofluorescence. In 19-wk-old human fetuses, Prox1
      and vascular endothelial growth factor receptor-3 (VEGFR-3) are coexpressed in
      LECs of lymphatic trunks and lymphatic capillaries. Prox1 is located in the
      nucleus, and its expression is mutually exclusive with that of the blood vascular
      marker PAL-E. Prox1 is a constitutive marker of LECs and is found in tissues of
      healthy adults and lymphedema patients. Blood vascular endothelial cells (BECs)
      of hemangiomas express CD31 and CD34, but not Prox1. A subset of these cells is
      positive for VEGFR-3. Lymphatics in the periphery of hemangiomas express Prox1
      and CD31, but not CD34. In lymphangiomas, LECs express Prox1, CD31, and VEGFR-3,
      but rarely CD34. In the stroma, spindle-shaped CD34-positive cells are present.
      We show that Prox1 is a reliable marker for LECs in normal and pathologic human
      tissues, coexpressed with VEGFR-3 and CD31. VEGFR-3 and CD34 are less reliable
      markers for LECs and BECs, respectively, because exceptions from their normal
      expression patterns are found in pathologic tissues.

PMID- 12060671
TI  - Fibroblast-dependent differentiation of human microvascular endothelial cells
      into capillary-like 3-dimensional networks.
AB  - An in vitro model has been developed to study migration, survival, proliferation,
      and capillary-like differentiation of human microvascular endothelial cells
      (HMVECs) in an environment that avoids tumor promoters and complex matrices.
      HMVEC monolayers were plated, then induced to form three-dimensional, capillary
      like networks by overlaying with human type I collagen followed by a second
      overlay of collagen with embedded fibroblasts. Detachment and migration of
      endothelial cells into the matrix was triggered within hours by the overlaying
      collagen, and the fibroblasts stimulated survival and formation of cords,
      vacuoles, tubes, and, after 4 to 5 days, capillary networks. The differentiation
      into branching capillary-like structures was dependent on direct fibroblast
      endothelial cell contact and was not achieved when fibroblasts were replaced by
      seven types of melanoma cells, which included radial and vertical growth phase
      primary and metastatic stages. Vascular endothelial growth factor (VEGF), when
      overexpressed in fibroblasts, stimulated endothelial cell proliferation and
      migration, whereas angiopoietin-1 (Ang-1) had only motogenic effects.
      Neutralizing antibodies against VEGF and blocking antibodies for VEGF-receptor 2
      (VEGFR2) significantly inhibited but not completely obliterated capillary network
      formation, suggesting that the VEGF signaling pathway is important but not
      exclusive and that other fibroblast-derived soluble factors and fibroblast
      endothelial cell contact are essential for endothelial cell survival and
      differentiation.

PMID- 12060672
TI  - Polyreactive antibodies to glatiramer acetate promote myelin repair in murine
      model of demyelinating disease.
AB  - Using a murine model of demyelinating disease, we demonstrate that remyelination
      of spinal cord axons is promoted by antibodies to glatiramer acetate (GA,
      Copolymer-1, Copaxone), a therapeutic agent for multiple sclerosis (MS).
      Glatiramer acetate is a mixture of randomly synthesized peptides that induces
      both T cell activation and antibody production in all treated individuals. These
      observations prompted us to compare the independent effects of adoptively
      transferred GA-reactive T cells and antibodies in mice with chronic inflammatory
      demyelination induced by Theiler's virus. Transferred T cells had no effect on
      lesion load or the extent of remyelination. Purified polyclonal GA antibodies
      also did not alter lesion load, which suggests that neither GA T cells or
      antibodies were pathogenic. On the contrary, GA antibodies enhanced the normally
      low level of remyelination in chronic lesions. The antibodies, which were
      primarily immunoglobulin (Ig) G1 and IgG2, cross-reacted with oligodendrocytes,
      perivascular infiltrating cells, astrocytes, and neurons in spinal cord sections.
      In glial cultures they bound subsets of early lineage oligodendrocytes and
      microglia. Thus, several mechanisms may have contributed to the promotion of
      remyelination. These results support the hypothesis that the antibody response in
      GA-treated patients is beneficial by facilitating repair of demyelinated lesions.

PMID- 12060673
TI  - Stressful death of T-ALL tumor cells after treatment with the anti-tumor agent
      Tetrocarcin-A.
AB  - The T-ALL cell lines CCRF-CEM and Jurkat were studied for their sensitivity
      toward apoptosis induced by tetrocarcin-A (TC-A), an antibacterial and antitumor
      agent isolated from the actinomycete Micromonospora. This substance promoted cell
      death via a mitochondrial signaling pathway, that is, by activation of Bid and
      Bax, loss of the mitochondrial transmembrane potential, release of cytochrome c,
      and activation of effector caspases, even under conditions of Bcl-2
      overexpression. Furthermore, sensitivity to TC-A was not dependent on expression
      of wild-type caspase-8. In contrast, this apoptotic pathway was inhibited
      markedly by pretreatment of cells with cycloheximide, an inhibitor of de novo
      protein synthesis. cDNA microarray chip analysis revealed that TC-A induced a
      significant up-regulation of members of the heat shock protein family known to be
      involved in the endoplasmic reticulum (ER)-stress-induced apoptotic program. The
      activation of caspase-12, the central inducer caspase involved in ER-stress by TC
      A treatment, is in concordance with this result. These results show that, in T
      ALL cells, TC-A induces an apoptotic machinery via mitochondrial and ER
      signaling, which is not inhibited by aberrant expression/function of important
      regulators of death receptor- and drug-induced apoptosis.

PMID- 12060674
TI  - Spontaneous oxidative stress and liver tumors in mice lacking methionine
      adenosyltransferase 1A.
AB  - In mammals, methionine metabolism occurs mainly in the liver via methionine
      adenosyltransferase-catalyzed conversion to S-adenosylmethionine. Of the two
      genes that encode methionine adenosyltransferase(MAT1Aand MAT2A), MAT1A is mainly
      expressed in adult liver whereas MAT2A is expressed in all extrahepatic tissues.
      Mice lacking MAT1A have reduced hepatic S-adenosylmethionine content and
      hyperplasia and spontaneously develop nonalcoholic steatohepatitis. In this
      study, we examined whether chronic hepatic S-adenosylmethionine deficiency
      generates oxidative stress and predisposes to injury and malignant
      transformation. Differential gene expression in MAT1A knockout mice was analyzed
      following the criteria of the Gene Ontology Consortium. Susceptibility of MAT1A
      knockout mice to CCl4-induced hepatotoxicity and malignant transformation was
      determined in 3- and 18-month-old mice, respectively. Analysis of gene expression
      profiles revealed an abnormal expression of genes involved in the metabolism of
      lipids and carbohydrates in MAT1A knockout mice, a situation that is reminiscent
      of that found in diabetes, obesity, and other conditions associated with
      nonalcoholic steatohepatitis. This aberrant expression of metabolic genes in the
      knockout mice was associated with hyperglycemia, increased hepatic CYP2E1 and
      UCP2 expression and triglyceride levels, and reduced hepatic glutathione content.
      The knockout animals have increased lipid peroxidation and enhanced sensitivity
      to CCl4-induced liver damage, which was largely due to increased CYP2E1
      expression because diallyl sulfide, an inhibitor of CYP2E1, prevented CCl4
      induced liver injury. Hepatocellular carcinoma developed in more than half of the
      knockout mice by 18 months of age. Taken together, our findings define a critical
      role for S-adenosylmethionine in maintaining normal hepatic function and
      tumorigenesis of the liver.

PMID- 12060675
TI  - Regulation of fibronectin matrix deposition and cell proliferation by the PINCH
      ILK-CH-ILKBP complex.
AB  - Alteration in renal glomerular mesangial cell growth and fibronectin matrix
      deposition is a hallmark of glomerulosclerosis, which ultimately leads to end
      stage renal failure. We have previously shown that the expression of integrin
      linked kinase (ILK), a cytoplasmic component of the cell-extracellular matrix
      contacts, is increased in mesangial cells in human patients with diabetic
      nephropathy. We show here that ILK forms a complex with PINCH and CH-ILKBP in
      primary mesangial cells, which are co-clustered at fibrillar adhesions, sites
      that are involved in fibronectin matrix deposition. To investigate functional
      significance of the PINCH-ILK-CH-ILKBP complex formation, we expressed the PINCH
      binding N-terminal fragment and the CH-ILKBP-binding C-terminal fragment of ILK,
      respectively, in mesangial cells by using an adenoviral expression system.
      Overexpression of either the N-terminal fragment or the C-terminal fragment of
      ILK effectively inhibited the PINCH-ILK-CH-ILKBP complex formation. Inhibition of
      the PINCH-ILK-CH-ILKBP complex formation significantly reduced fibronectin matrix
      deposition and inhibited cell proliferation. These results indicate that the
      PINCH-ILK-CH-ILKBP complex is critically involved in the regulation of mesangial
      fibronectin matrix deposition and cell proliferation, and suggest that it may
      potentially serve as a useful target in the therapeutic control of progressive
      renal failure and other pathological processes involving abnormal cell
      proliferation and fibronectin matrix deposition.

PMID- 12060676
TI  - Glutathione depletion enforces the mitochondrial permeability transition and
      causes cell death in Bcl-2 overexpressing HL60 cells.
AB  - Bcl-2, a protein that blocks apoptosis by inhibiting the mitochondrial
      permeability transition (MPT) and release of cytochrome c appears to affect
      normal mitochondrial function by altering electron flow and increasing rates of
      reactive oxygen species (ROS) production. In this study, we show that glutathione
      (GSH) depletion induces ROS production and selective toxicity in HL60 cells that
      overexpress Bcl-2 compared with neomycin vector control cells. Toxicity was
      mediated by the MPT because it was blocked with the adenine nucleotide
      translocator (ANT) ligand bongkrekic acid and resulted in mitochondrial
      cytochrome c release, caspase 3 activation, and DNA fragmentation, indicating the
      involvement of an apoptotic pathway. Respiratory chain inhibitors stigmatellin
      and antimycin A, which inhibit Qo and Qi sites of respiratory chain complex III,
      respectively, blocked ROS production, preserved the redox state of protein
      thiols, and prevented cell death. These results indicate that in the absence of
      GSH, endogenous ROS generated at respiratory complex III induce MPT independently
      of Bcl-2. The results also suggest a new model for MPT in which the central pore
      protein ANT is regulated by adenine nucleotide and the activity of mitochondrial
      respiratory complex III.

PMID- 12060677
TI  - Properties of triple helices formed by parallel-stranded hairpins containing 8
      aminopurines.
AB  - Parallel-stranded hairpins with a polypyrimidine sequence linked to a
      complementary purine carrying 8-aminopurines such as 8-aminoadenine, 8
      aminoguanine and 8-aminohypoxanthine bind polypyrimidine sequences complementary
      (in an antiparallel sense) to the purine part by a triple helix. The relative
      stabilities of triplexes were assessed by UV-absorption melting experiments as a
      function of pH and salt concentration. Hairpins carrying 8-aminopurines give very
      stable triple helical structures even at neutral pH, as confirmed by gel-shift
      experiments, circular dichroism and nuclear magnetic resonance spectroscopy. The
      modified hairpins may be redesigned to cope with small interruptions in the
      polypyrimidine target sequence.

PMID- 12060678
TI  - Interaction among silkworm ribosomal proteins P1, P2 and P0 required for
      functional protein binding to the GTPase-associated domain of 28S rRNA.
AB  - Acidic ribosomal phosphoproteins P0, P1 and P2 were isolated in soluble form from
      silkworm ribosomes and tested for their interactions with each other and with RNA
      fragments corresponding to the GTPase-associated domain of residues 1030-1127
      (Escherichia coli numbering) in silkworm 28S rRNA in vitro. Mixing of P1 and P2
      formed the P1-P2 heterodimer, as demonstrated by gel mobility shift and chemical
      crosslinking. This heterodimer, but neither P1 or P2 alone, tightly bound to P0
      and formed a pentameric complex, presumably as P0(P1-P2)2, assumed from its
      molecular weight derived from sedimentation analysis. Complex formation strongly
      stimulated binding of P0 to the GTPase-associated RNA domain. The protein complex
      and eL12 (E.coli L11-type), which cross-bound to the E.coli equivalent RNA
      domain, were tested for their function by replacing with the E.coli counterparts
      L10.L7/L12 complex and L11 on the rRNA domain within the 50S subunits. Both P1
      and P2, together with P0 and eL12, were required to activate ribosomes in
      polyphenylalanine synthesis dependent on eucaryotic elongation factors as well as
      eEF-2-dependent GTPase activity. The results suggest that formation of the P1-P2
      heterodimer is required for subsequent formation of the P0(P1-P2)2 complex and
      its functional rRNA binding in silkworm ribosomes.

PMID- 12060679
TI  - Mutational analysis of conserved residues in HhaI DNA methyltransferase.
AB  - HhaI DNA methyltransferase belongs to the C5-cytosine methyltransferase family,
      which is characterized by the presence of a set of highly conserved amino acids
      and motifs present in an invariant order. HhaI DNA methyltransferase has been
      subjected to a lot of biochemical and crystallographic studies. A number of
      issues, especially the role of the conserved amino acids in the methyltransferase
      activity, have not been addressed. Using sequence comparison and structural data,
      a structure-guided mutagenesis approach was undertaken, to assess the role of
      conserved amino acids in catalysis. Site-directed mutagenesis was performed on
      amino acids involved in cofactor S-adenosyl-L-methionine (AdoMet) binding (Phe18,
      Trp41, Asp60 and Leu100). Characterization of these mutants, by in vitro /in vivo
      restriction assays and DNA/AdoMet binding studies, indicated that most of the
      residues present in the AdoMet-binding pocket were not absolutely essential. This
      study implies plasticity in the recognition of cofactor by HhaI DNA
      methyltransferase.

PMID- 12060680
TI  - Gene rearrangements induced by the DNA double-strand cleaving agent
      neocarzinostatin: conservative non-homologous reciprocal exchanges in an
      otherwise stable genome.
AB  - Among a collection of 74 aprt mutations induced by treatment of plateau phase
      Chinese hamster ovary CHO cells with the radiomimetic DNA double-strand cleaving
      agent neocarzinostatin, nine were large-scale rearrangements. Molecular analysis
      indicated that all nine were highly conservative, non-homologous reciprocal
      exchanges, most of which were intrachromosomal as determined by fluorescence in
      situ hybridization. All but one of the parental sequences contained potential
      double-strand cleavage sites positioned such that the observed rearrangements
      could be explained by drug-induced double-strand breakage followed by trimming,
      templated patching and ligation of the exchanged ends. Predicted non
      complementary 3' overhangs were often preserved in the newly formed junctions,
      suggesting alignment-based fill-in of the overhangs. Banding of metaphase spreads
      of these mutants, and of a number of mutants induced by the functionally similar
      compound bleomycin, revealed that bleomycin-induced reciprocal exchange mutants
      had multiple additional chromosome alterations and considerable chromosomal
      heterogeneity within each mutant line. In contrast, neocarzinostatin-induced
      reciprocal exchange mutants, as well as bleomycin-induced base substitution and
      single base deletion mutants, retained stable pseudodiploid karyotypes similar to
      that of the parent line. Thus, some reciprocal exchanges arising from misjoining
      of double-strand breaks were associated with global chromosomal instability,
      while other ostensibly similar events were not.

PMID- 12060681
TI  - Regulated HIV-2 RNA dimerization by means of alternative RNA conformations.
AB  - The dimer initiation site (DIS) hairpin of the HIV-2 untranslated leader RNA
      mediates in vitro dimerization through 'loop-loop kissing' of a loop-exposed
      palindrome sequence. Premature RNA dimerization must be prevented during the
      retroviral life cycle. A regulatory mechanism has been proposed for the HIV-1
      leader RNA that can adopt an alternative conformation in which the DIS motif is
      effectively masked by long-distance base pairing with upstream leader sequences.
      We now report that HIV-2 RNA dimerization is also regulated. Sequestering of the
      DIS motif by base pairing interactions with downstream leader sequences mediates
      a switch to a dimerization-impaired conformation. The existence of two
      alternative conformations of the HIV-2 leader RNA is supported by UV melting
      experiments. Furthermore, the equilibrium between the two conformations can be
      shifted by annealing of antisense oligonucleotides or by deletion of certain
      leader regions. These measures have a profound impact on the dimerization
      properties of the transcript, demonstrating a mutual exclusivity between the
      alternative conformation and dimerization, similar to what has been described for
      the HIV-1 leader. The overall resemblance in regulation of HIV-1 and HIV-2 RNA
      dimerization suggests that a similar mechanism may be operating in other
      lentiviruses and perhaps all retroviridae.

PMID- 12060682
TI  - DNA bending, compaction and negative supercoiling by the architectural protein
      Sso7d of Sulfolobus solfataricus.
AB  - Members of the Sso7d/Sac7d family are small, abundant, non-specific DNA-binding
      proteins of the hyperthermophilic Archaea SULFOLOBUS: Crystal structures of these
      proteins in complex with oligonucleotides showed that they induce changes in the
      helical twist and marked DNA bending. On this basis they have been suggested to
      play a role in organising chromatin structures in these prokaryotes, which lack
      histones. We report functional in vitro assays to investigate the effects of the
      observed Sso7d-induced structural modifications on DNA geometry and topology. We
      show that binding of multiple Sso7d molecules to short DNA fragments induces
      significant curvature and reduces the stiffness of the complex. Sso7d induces
      negative supercoiling of DNA molecules of any topology (relaxed, positively or
      negatively supercoiled) and in physiological conditions of temperature and
      template topology. Binding of Sso7d induces compaction of positively supercoiled
      and relaxed DNA molecules, but not of negatively supercoiled ones. Finally, Sso7d
      inhibits the positive supercoiling activity of the thermophile-specific enzyme
      reverse gyrase. The proposed biological relevance of these observations is that
      these proteins might model the behaviour of DNA in constrained chromatin
      environments.

PMID- 12060683
TI  - Changing homeodomain residues 2 and 3 of Hoxa1 alters its activity in a cell-type
      and enhancer dependent manner.
AB  - The second and third amino acid residues of the N-terminal arm of most Hox
      protein homeodomains are basic (lysine or arginine), whereas they are asparagine
      and alanine, respectively, in the Hoxa1 homeodomain. Previous reports pinpointed
      these residues as specificity determinants in the function of Hoxa1 when it is
      acting as a monomer. However, in vitro data supported that these residues do not
      influence the target specificity of Hoxa1 in Pbx1a-Hoxa1 heterodimers. Here, we
      have analysed the transcriptional activity of a Hoxa1(NA-KR) mutant for which the
      asparagine and alanine residues of the homeodomain have been replaced by lysine
      and arginine, respectively. Comparison between the wild-type and mutant Hoxa1
      reveals that they show distinct activity on the TSEII enhancer of the
      somatostatin gene, but that they are equally active in the presence of Pbx and
      Prep cofactors. This therefore corroborates the biochemical evidence having shown
      that the second and third residues of the homeodomain do not contribute to the
      DNA binding of Hoxa1-Pbx dimers. However, on the hoxb1 autoregulatory enhancer,
      Hoxa1 and Hoxa1(NA-KR) may display distinct activity despite the presence of Pbx,
      in a cell-type dependent manner. Therefore, our data suggest that, depending on
      the enhancer, these residues may contribute to the functional specificity of
      Hoxa1 and that this contribution may not be abrogated by the interaction with
      Pbx.

PMID- 12060684
TI  - Solution structure of dAATAA and dAAUAA DNA bulges.
AB  - The NMR structure analysis is described for two DNA molecules of identical stem
      sequences with a five base loop containing a pyrimidine, thymin or uracil, in
      between purines. These five unpaired nucleotides are bulged out and are known to
      induce a kink in the duplex structure. The dAATAA bulge DNA is kinked between the
      third and the fourth nucleotide. This contrasts with the previously studied
      dAAAAA bulge DNA where we found a kink between the fourth and fifth nucleotide.
      The total kinking angle is approximately 104 degrees for the dAATAA bulge. The
      findings were supported by electrophoretic data and fluorescence resonance energy
      transfer measurements of a similar DNA molecule end-labeled by suitable
      fluorescent dyes. For the dAAUAA bulge the NMR data result in a similar structure
      as reported for the dAATAA bulge with a kinking angle of approximately 87
      degrees. The results are discussed in comparison with a rAAUAA RNA bulge found in
      a group I intron. Generally, the sequence-dependent structure of bulges is
      important to understand the role of DNA bulges in protein recognition.

PMID- 12060685
TI  - Investigating the structural basis of purine specificity in the structures of MS2
      coat protein RNA translational operator hairpins.
AB  - We have determined the structures of complexes between the phage MS2 coat protein
      and variants of the replicase translational operator in order to explore the
      sequence specificity of the RNA-protein interaction. The 19-nt RNA hairpins
      studied have substitutions at two positions that have been shown to be important
      for specific binding. At one of these positions, -10, which is a bulged adenosine
      (A) in the stem of the wild-type operator hairpin, substitutions were made with
      guanosine (G), cytidine (C) and two non-native bases, 2-aminopurine (2AP) and
      inosine (I). At the other position, -7 in the hairpin loop, the native adenine
      was substituted with a cytidine. Of these, only the G-10, C-10 and C-7 variants
      showed interpretable density for the RNA hairpin. In spite of large differences
      in binding affinities, the structures of the variant complexes are very similar
      to the wild-type operator complex. For G-10 substitutions in hairpin variants
      that can form bulges at alternative places in the stem, the binding affinity is
      low and a partly disordered conformation is seen in the electron density maps.
      The affinity is similar to that of wild-type when the base pairs adjacent to the
      bulged nucleotide are selected to avoid alternative conformations. Both purines
      bind in a very similar way in a pocket in the protein. In the C-10 variant, which
      has very low affinity, the cytidine is partly inserted in the protein pocket
      rather than intercalated in the RNA stem. Substitution of the wild-type adenosine
      at position -7 by pyrimidines gives strongly reduced affinities, but the
      structure of the C-7 complex shows that the base occupies the same position as
      the A-7 in the wild-type RNA. It is stacked in the RNA and makes no direct
      contact with the protein.

PMID- 12060686
TI  - UV light-damaged DNA and its interaction with human replication protein A: an
      atomic force microscopy study.
AB  - We have imaged a non-damaged and UV-damaged DNA fragment and its complexes with
      human replication protein A (RPA) using tapping mode atomic force microscopy
      (AFM). For imaging, molecules were immobilized under nearly physiological
      conditions on mica surfaces. Quantitative sizing of the 538 bp DNA before and
      after UV light treatment shows a reduction in the contour and persistence lengths
      and mean square end-to-end distance as a consequence of UV irradiation. Complexes
      of the UV-damaged DNA with RPA, an essential component of the initial steps of
      nucleotide excision repair, can be detected at high resolution with AFM and
      reveal conformational changes of the DNA related to complex formation. By phase
      image analysis we are able to discriminate between protein and DNA in the
      complexes. The DNA molecules are found to 'wrap' around the RPA, which in turn
      results in a considerable reduction in its apparent contour length.

PMID- 12060687
TI  - DNA binding of the transcription activator protein MelR from Escherichia coli and
      its C-terminal domain.
AB  - MelR is an Escherichia coli transcription factor belonging to the AraC family. It
      activates expression of the melAB operon in response to melibiose. Full-length
      MelR (MelR303) binds to two pairs of sites upstream of the melAB transcription
      start site, denoted sites 1' and 1 and sites 2 and 2', and to a fifth site, R,
      which overlaps the divergent melR promoter. The C-terminal domain of MelR
      (MelR173) does not activate transcription. Here we show that, like MelR303, when
      MelR173 binds to sites 1 and 2 it recruits CRP to bind between these sites.
      Hence, the C-terminal domain is involved in heterologous interactions. MelR173
      binds to the R site, which has 11 of 18 bp identical to sites 1 and 2 but,
      surprisingly, does not bind to site 1', which has 12 of 18 bp identical, nor to
      site 2'. Using electrophoretic mobility shift assays, we show that the binding of
      MelR303 to sites 1' and 2' is due to cooperative binding with the adjacent site.
      This homologous cooperativity requires the N-terminal domain of the protein.
      Activation of the melAB promoter requires MelR to occupy site 2', which overlaps
      the -35 hexamer. Hence, both domains of MelR are required for transcription
      activation.

PMID- 12060688
TI  - Design of a novel triple helix-forming oligodeoxyribonucleotide directed to the
      major promoter of the c-myc gene.
AB  - Altered expression of c-myc is implicated in pathogenesis and progression of many
      human cancers. Triple helix-forming oligonucleotides (TFOs) directed to a
      polypurine/polypyrimidine sequence in a critical regulatory region near the c-myc
      P2 promoter have been shown to inhibit c-myc transcription in vitro and in cells.
      However, these guanine-rich TFOs had moderate binding affinity and required high
      concentrations for activity. The 23 bp myc P2 sequence is split equally into AT-
      and GC-rich tracts. Gel mobility analysis of a series of short TFOs directed in
      parallel and anti-parallel orientation to the purine strand of each tract showed
      that only parallel CT and anti-parallel GT TFOs formed stable triplex on the AT-
      and GC-rich tracts, respectively. A novel full-length GTC TFO was designed to
      bind simultaneously in parallel and anti-parallel orientation to the polypurine
      strand. Gel-shift and footprinting assays showed that the new TFO formed a triple
      helix in physiological conditions with significantly higher affinity than an anti
      parallel TFO. Protein-binding assays showed that 1 microM GTC TFO inhibited
      binding of nuclear transcription factors to the P2 promoter sequence. The novel
      TFO can be developed into a potent antigene agent, and its design strategy
      applied to similar genomic sequences, thus expanding the TFO repertoire.

PMID- 12060689
TI  - Dictionary-driven prokaryotic gene finding.
AB  - Gene identification, also known as gene finding or gene recognition, is among the
      important problems of molecular biology that have been receiving increasing
      attention with the advent of large scale sequencing projects. Previous strategies
      for solving this problem can be categorized into essentially two schools of
      thought: one school employs sequence composition statistics, whereas the other
      relies on database similarity searches. In this paper, we propose a new gene
      identification scheme that combines the best characteristics from each of these
      two schools. In particular, our method determines gene candidates among the ORFs
      that can be identified in a given DNA strand through the use of the Bio
      Dictionary, a database of patterns that covers essentially all of the currently
      available sample of the natural protein sequence space. Our approach relies
      entirely on the use of redundant patterns as the agents on which the presence or
      absence of genes is predicated and does not employ any additional evidence, e.g.
      ribosome-binding site signals. The Bio-Dictionary Gene Finder (BDGF), the
      algorithm's implementation, is a single computational engine able to handle the
      gene identification task across distinct archaeal and bacterial genomes. The
      engine exhibits performance that is characterized by simultaneous very high
      values of sensitivity and specificity, and a high percentage of correctly
      predicted start sites. Using a collection of patterns derived from an old (June
      2000) release of the Swiss-Prot/TrEMBL database that contained 451 602 proteins
      and fragments, we demonstrate our method's generality and capabilities through an
      extensive analysis of 17 complete archaeal and bacterial genomes. Examples of
      previously unreported genes are also shown and discussed in detail.

PMID- 12060690
TI  - Improved detection of small deletions in complex pools of DNA.
AB  - About 40% of the genes in the nematode Caenorhabditis elegans have homologs in
      humans. Based on the history of this model system, it is clear that the
      application of genetic methods to the study of this set of genes would provide
      important clues to their function in humans. To facilitate such genetic studies,
      we are engaged in a project to derive deletion alleles in every gene in this set.
      Our standard methods make use of nested PCR to hunt for animals in mutagenized
      populations that carry deletions at a given locus. The deletion bearing animals
      exist initially in mixed populations where the majority of the animals are wild
      type at the target. Therefore, the production of the PCR fragment representing
      the deletion allele competes with the production of the wild type fragment. The
      size of the deletion fragment relative to wild type determines whether it can
      compete to a level where it can be detected above the background. Using our
      standard conditions, we have found that when the deletion is <600 bp, the
      deletion fragment does not compete effectively with the production of the wild
      type fragment in PCR. Therefore, although our standard methods work well to
      detect mutants with deletions >600 bp, they do not work well to detect mutants
      with smaller deletions. Here we report a new strategy to detect small deletion
      alleles in complex DNA pools. Our new strategy is a modification of our standard
      PCR based screens. In the first round of the nested PCR, we include a third PCR
      primer between the two external primers. The presence of this third primer leads
      to the production of three fragments from wild type DNA. We configure the system
      so that two of these three fragments cannot serve as a template in the second
      round of the nested PCR. The addition of this third primer, therefore, handicaps
      the amplification from wild type template. On the other hand, the amplification
      of mutant fragments where the binding site for the third primer is deleted is
      unabated. Overall, we see at least a 500-fold increase in the sensitivity for
      small deletion fragments using our new method. Using this new method, we report
      the recovery of new deletion alleles within 12 C.elegans genes.

PMID- 12060691
TI  - High-throughput genotyping of single nucleotide polymorphisms using new biplex
      invader technology.
AB  - The feasibility of large-scale genome-wide association studies of complex human
      disorders depends on the availability of accurate and efficient genotyping
      methods for single nucleotide polymorphisms (SNPs). We describe a new platform of
      the invader assay, a biplex assay, where both alleles are interrogated in a
      single reaction tube. The assay was evaluated on over 50 different SNPs, with
      over 20 SNPs genotyped in study cohorts of over 1500 individuals. We assessed the
      usefulness of the new platform in high-throughput genotyping and compared its
      accuracy to genotyping results obtained by the traditional monoplex invader
      assay, TaqMan genotyping and sequencing data. We present representative data for
      two SNPs in different genes (CD36 and protein tyrosine phosphatase 1beta) from a
      study cohort comprising over 1500 individuals with high or low-normal blood
      pressure. In this high-throughput application, the biplex invader assay is very
      accurate, with an error rate of <0.3% and a failure rate of 1.64%. The set-up of
      the assay is highly automated, facilitating the processing of large numbers of
      samples simultaneously. We present new analysis tools for the assignment of
      genotypes that further improve genotyping success. The biplex invader assay with
      its automated set-up and analysis offers a new efficient high-throughput
      genotyping platform that is suitable for association studies in large study
      cohorts.

PMID- 12060692
TI  - Microarray optimizations: increasing spot accuracy and automated identification
      of true microarray signals.
AB  - In this paper, fluorescent microarray images and various analysis techniques are
      described to improve the microarray data acquisition processes. Signal
      intensities produced by rarely expressed genes are initially correctly detected,
      but they are often lost in corrections for background, log or ratio. Our analyses
      indicate that a simple correlation between the mean and median signal intensities
      may be the best way to eliminate inaccurate microarray signals. Unlike
      traditional quality control methods, the low intensity signals are retained and
      inaccurate signals are eliminated in this mean and median correlation. With
      larger amounts of microarray data being generated, it becomes increasingly more
      difficult to analyze data on a visual basis. Our method allows for the automatic
      quantitative determination of accurate and reliable signals, which can then be
      used for normalization. We found that a mean to median correlation of 85% or
      higher not only retains more data than current methods, but the retained data is
      more accurate than traditional thresholds or common spot flagging algorithms. We
      have also found that by using pin microtapping and microvibrations, we can
      control spot quality independent from initial PCR volume.

PMID- 12060693
TI  - An electrochemical detection scheme for identification of single nucleotide
      polymorphisms using hairpin-forming probes.
AB  - Single nucleotide polymorphisms are implicated as having a significant role in
      regulating growth, development and, thereby, human health and disease. We have
      developed a method for identifying single nucleotide genetic alterations by
      combining hairpin-forming DNA probes and electrochemical detection of sandwich
      DNA hybridization. Incorporation of hairpin-forming competitor probes and the
      catalyzed reporter deposition amplification system further improves assay
      specificity by 7-fold and sensitivity by 100-fold. We have demonstrated that the
      system successfully identified the factor V Leiden mutations from human blood
      specimens.

PMID- 12060694
TI  - A universal method to produce in vitro transcripts with homogeneous 3' ends.
AB  - A method is described that allows a general drawback of in vitro transcription
      assays to be overcome: RNA polymerases tend to add extra nucleotides to the RNA
      3' end that are not encoded in the linearized DNA template. Furthermore, these
      polymerases show a considerable rate of premature termination close to the RNA's
      3' end. These features lead to a decreased yield of full-length transcripts and
      often make it difficult to determine and isolate the correctly transcribed full
      length RNA. The hammerhead ribozyme is frequently used in cis to cleave off these
      extra nucleotides. However, the upstream sequence requirements of this ribozyme
      restrict its general usability. In contrast, the hepatitis delta virus ribozyme
      has no such requirements and can therefore be applied to any RNA sequence in cis.
      Due to the catalytic activity of the ribozyme, the desired transcript is released
      as an RNA molecule with a homogeneous 3' end. The resulting 2',3'-cyclo-phosphate
      group of the released RNA can be easily and efficiently removed by T4
      polynucleotide kinase treatment. The presented method can be applied for
      virtually any sequence to be transcribed and is therefore superior to other
      ribozyme strategies, suggesting possible applications in every field where
      transcripts with homogeneous 3' ends are required.

PMID- 12060695
TI  - Relative quantification of 40 nucleic acid sequences by multiplex ligation
      dependent probe amplification.
AB  - We describe a new method for relative quantification of 40 different DNA
      sequences in an easy to perform reaction requiring only 20 ng of human DNA.
      Applications shown of this multiplex ligation-dependent probe amplification
      (MLPA) technique include the detection of exon deletions and duplications in the
      human BRCA1, MSH2 and MLH1 genes, detection of trisomies such as Down's syndrome,
      characterisation of chromosomal aberrations in cell lines and tumour samples and
      SNP/mutation detection. Relative quantification of mRNAs by MLPA will be
      described elsewhere. In MLPA, not sample nucleic acids but probes added to the
      samples are amplified and quantified. Amplification of probes by PCR depends on
      the presence of probe target sequences in the sample. Each probe consists of two
      oligonucleotides, one synthetic and one M13 derived, that hybridise to adjacent
      sites of the target sequence. Such hybridised probe oligonucleotides are ligated,
      permitting subsequent amplification. All ligated probes have identical end
      sequences, permitting simultaneous PCR amplification using only one primer pair.
      Each probe gives rise to an amplification product of unique size between 130 and
      480 bp. Probe target sequences are small (50-70 nt). The prerequisite of a
      ligation reaction provides the opportunity to discriminate single nucleotide
      differences.

PMID- 12060696
TI  - Ferrocene conjugates of dUTP for enzymatic redox labelling of DNA.
AB  - Two ferrocene-labelled analogues of dTTP, 5-(3-ferrocenecarboxamidopropenyl-1) 2'
      deoxyuridine 5'-triphosphate (Fc1-dUTP) and 5-(3-ferroceneacet-amidopropenyl-1)
      2'-deoxyuridine 5'-triphosphate (Fc2-dUTP) have been produced to demonstrate the
      incorporation of redox labels into DNA by polymerases. Cyclic voltammetry
      indicates that the ferrocenyl moieties display reversible redox behaviour in
      aqueous buffer with E(1/2) values of 398 (Fc1-dUTP) and 260 mV (Fc2-dUTP) versus
      Ag/AgCl. Primer extension by the proofreading enzymes Klenow fragment and T4 DNA
      polymerase shows that Fc1-dUTP is efficiently incorporated into DNA during
      synthesis, including incorporation of two successive modified nucleotides.
      Production of a 998 bp amplicon by Tth DNA polymerase demonstrates that Fc1-dUTP
      is also a satisfactory substrate for PCR. Despite its structural similarity, Fc2
      dUTP acts predominantly as a terminator with the polymerases employed here. UV
      melting analysis of a 37mer duplex containing five Fc1-dU residues reveals that
      the labelled nucleotide introduces only a modest helix destabilisation, with T(m)
      = 71 versus 75 degrees C for the corresponding natural construct. Modified DNA is
      detected at femtomole levels using a HPLC system with a coulometric detector. The
      availability of simple and effective enzymatic labelling strategies should
      promote the further development of electrochemical detection in nucleic acid
      analysis.

PMID- 12060697
TI  - Unmodified Cre recombinase crosses the membrane.
AB  - Site-specific recombination in genetically modified cells can be achieved by the
      activity of Cre recombinase from bacteriophage P1. Commonly an expression vector
      encoding Cre is introduced into cells; however, this can lead to undesired side
      effects. Therefore, we tested whether cell-permeable Cre fusion proteins can be
      directly used for lox-specific recombination in a cell line tailored to shift
      from red to green fluorescence after loxP-specific recombination. Comparison of
      purified recombinant Cre proteins with and without a heterologous 'protein
      transduction domain' surprisingly showed that the unmodified Cre recombinase
      already possesses an intrinsic ability to cross the membrane border. Addition of
      purified recombinant Cre enyzme to primary bone marrow cells isolated from
      transgenic C/EBPalpha(fl/fl) mice also led to excision of the 'floxed' C/EBPalpha
      gene, thus demonstrating its potential for in vivo applications. We conclude that
      Cre enyzme itself or its intrinsic membrane-permeating moiety are attractive
      tools for direct manipulation of mammalian cells.

PMID- 12060698
TI  - Integration of DNA ligation and rolling circle amplification for the homogeneous,
      end-point detection of single nucleotide polymorphisms.
AB  - Association studies using common sequence variants or single nucleotide
      polymorphisms (SNPs) may provide a powerful approach to dissect the genetic
      inheritance of common complex traits. Such studies necessitate the development of
      cost-effective, high throughput technologies for scoring SNPs. The method
      described in this paper for the co-detection of both alleles of a SNP in a single
      homogeneous reaction combines the specificity of a high fidelity DNA ligation
      step with the power of rolling circle amplification. The incorporation of
      Amplifluor energy transfer primers enables signal detection in a homogeneous
      format, making this approach highly amenable to automation. The adaptation of the
      genotyping method for high throughput screening using conventional liquid
      handling systems is described.

PMID- 12060699
TI  - Label-free hybridization detection of a single nucleotide mismatch by
      immobilization of molecular beacons on an agarose film.
AB  - We developed a new technique to immobilize a set of molecular beacons on an
      agarose film-coated slide and found that it has the ability to identify a single
      nucleotide difference in label-free DNA targets. The annealing properties,
      specificity and hybridization dynamics of the present technique were compared
      with those of the conventional technique that directly immobilizes molecular
      beacons on a planar glass slide. It is demonstrated that the molecular beacon
      array on an agarose film has high quench efficiency, an excellent discrimination
      ratio for single nucleotide mismatches and a short detection time. We hypothesize
      that such a low fluorescence background and high specificity molecular beacon
      array will find practical applications in label-free, high-throughput mutation
      analysis and disease diagnosis.

PMID- 12060700
TI  - Direct micro-haplotyping by multiple double PCR amplifications of specific
      alleles (MD-PASA).
AB  - Analysis of haplotypes is an important tool in population genetics, familial
      heredity and gene mapping. Determination of haplotypes of multiple single
      nucleotide polymorphisms (SNPs) or other simple mutations is time consuming and
      expensive when analyzing large populations, and often requires the help of
      computational and statistical procedures. Based on double PCR amplification of
      specific alleles, described previously, we have developed a simple, rapid and low
      cost method for direct haplotyping of multiple SNPs and simple mutations found
      within relatively short specific regions or genes (micro-haplotypes). Using this
      method, it is possible to directly determine the physical linkage of multiple
      heterozygous alleles, by conducting a series of double allele-specific PCR
      amplification sets with simple analysis by gel electrophoresis. Application of
      the method requires prior information as to the sequence of the segment to be
      haplotyped, including the polymorphic sites. We applied the method to haplotyping
      of nine sites in the chicken HSP108 gene. One of the haplotypes in the population
      apparently arose by recombination between two existing haplotypes, and we were
      able to locate the point of recombination within a segment of 19 bp. We
      anticipate rapidly growing needs for SNP haplotyping in human (medical and
      pharmacogenetics), animal and plant genetics; in this context, the multiple
      double PCR amplifications of specific alleles (MD-PASA) method offers a useful
      haplotyping tool.

PMID- 12060701
TI  - Methylation of histone H3 Lys 4 in coding regions of active genes.
AB  - Posttranslational modifications of histone tails regulate chromatin structure and
      transcription. Here we present global analyses of histone acetylation and histone
      H3 Lys 4 methylation patterns in yeast. We observe a significant correlation
      between acetylation of histones H3 and H4 in promoter regions and transcriptional
      activity. In contrast, we find that dimethylation of histone H3 Lys 4 in coding
      regions correlates with transcriptional activity. The histone methyltransferase
      Set1 is required to maintain expression of these active, promoter-acetylated, and
      coding region-methylated genes. Global comparisons reveal that genomic regions
      deacetylated by the yeast enzymes Rpd3 and Hda1 overlap extensively with Lys 4
      hypo- but not hypermethylated regions. In the context of recent studies showing
      that Lys 4 methylation precludes histone deacetylase recruitment, we conclude
      that Set1 facilitates transcription, in part, by protecting active coding regions
      from deacetylation.

PMID- 12060702
TI  - Structure theorems for game trees.
AB  - Kohlberg and Mertens [Kohlberg, E. & Mertens, J. (1986) Econometrica 54, 1003
      1039] proved that the graph of the Nash equilibrium correspondence is
      homeomorphic to its domain when the domain is the space of payoffs in normal-form
      games. A counterexample disproves the analog for the equilibrium outcome
      correspondence over the space of payoffs in extensive-form games, but we prove an
      analog when the space of behavior strategies is perturbed so that every path in
      the game tree has nonzero probability. Without such perturbations, the graph is
      the closure of the union of a finite collection of its subsets, each
      diffeomorphic to a corresponding path-connected open subset of the space of
      payoffs. As an application, we construct an algorithm for computing equilibria of
      an extensive-form game with a perturbed strategy space, and thus approximate
      equilibria of the unperturbed game.

PMID- 12060703
TI  - Recognition of a virus-encoded ligand by a natural killer cell activation
      receptor.
AB  - Natural killer (NK) cells express inhibitory and activation receptors that
      recognize MHC class I-like molecules on target cells. These receptors may be
      involved in the critical role of NK cells in controlling initial phases of
      certain viral infections. Indeed, the Ly49H NK cell activation receptor confers
      in vivo genetic resistance to murine cytomegalovirus (MCMV) infections, but its
      ligand was previously unknown. Herein, we use heterologous reporter cells to
      demonstrate that Ly49H recognizes MCMV-infected cells and a ligand encoded by
      MCMV itself. Exploiting a bioinformatics approach to the MCMV genome, we find at
      least 11 ORFs for molecules with previously unrecognized features of predicted
      MHC-like folds and limited MHC sequence homology. We identify one of these, m157,
      as the ligand for Ly49H. m157 triggers Ly49H-mediated cytotoxicity, and cytokine
      and chemokine production by freshly isolated NK cells. We hypothesize that the
      other ORFs with predicted MHC-like folds may be involved in immune evasion or
      interactions with other NK cell receptors.

PMID- 12060704
TI  - SOS-induced DNA polymerases enhance long-term survival and evolutionary fitness.
AB  - Escherichia coli encodes three SOS-induced DNA polymerases: pol II, pol IV, and
      pol V. We show here that each of these polymerases confers a competitive fitness
      advantage during the stationary phase of the bacterial life cycle, in the absence
      of external DNA-damaging agents known to induce the SOS response. When grown
      individually, wild-type and SOS pol mutants exhibit indistinguishable temporal
      growth and death patterns. In contrast, when grown in competition with wild-type
      E. coli, mutants lacking one or more SOS polymerase suffer a severe reduction in
      fitness. These mutants also fail to express the "growth advantage in stationary
      phase" phenotype as do wild-type strains, instead expressing two additional new
      types of "growth advantage in stationary phase" phenotype. These polymerases
      contribute to survival by providing essential functions to ensure replication of
      the chromosome and by generating genetic diversity.

PMID- 12060705
TI  - Assembling the glycopeptide antibiotic scaffold: The biosynthesis of A47934 from
      Streptomyces toyocaensis NRRL15009.
AB  - The glycopeptide antibiotics vancomycin and teicoplanin are vital components of
      modern anti-infective chemotherapy exhibiting outstanding activity against Gram
      positive pathogens including members of the genera Streptococcus, Staphylococcus,
      and Enterococcus. These antibiotics also provide fascinating examples of the
      chemical and associated biosynthetic complexity exploitable in the synthesis of
      natural products by actinomycetes group of bacteria. We report the sequencing and
      annotation of the biosynthetic gene cluster for the glycopeptide antibiotic from
      Streptomyces toyocaensis NRRL15009, the first complete sequence for a teicoplanin
      class glycopeptide. The cluster includes 34 ORFs encompassing 68 kb and includes
      all of the genes predicted to be required to synthesize and regulate its
      biosynthesis. The gene cluster also contains ORFs encoding enzymes responsible
      for glycopeptide resistance. This role was confirmed by insertional inactivation
      of the d-Ala-d-lactate ligase, vanAst, which resulted in the predicted -sensitive
      phenotype and impaired antibiotic biosynthesis. These results provide increased
      understanding of the biosynthesis of these complex natural products.

PMID- 12060706
TI  - Computational subunits of visual cortical neurons revealed by artificial neural
      networks.
AB  - A crucial step toward understanding visual processing is to obtain a
      comprehensive description of the relationship between visual stimuli and neuronal
      responses. Many neurons in the visual cortex exhibit nonlinear responses, making
      it difficult to characterize their stimulus-response relationships. Here, we
      recorded the responses of primary visual cortical neurons of the cat to
      spatiotemporal random-bar stimuli and trained artificial neural networks to
      predict the response of each neuron. The random initial connections in the
      networks consistently converged to regular patterns. Analyses of these connection
      patterns showed that the response of each complex cell to the random-bar stimuli
      could be well approximated by the sum of a small number of subunits resembling
      simple cells. The direction selectivity of each complex cell measured with
      drifting gratings was also well predicted by the combination of these subunits,
      indicating the generality of the model. These results are consistent with a
      simple functional model for complex cells and demonstrate the usefulness of the
      neural network method for revealing the stimulus-response transformations of
      nonlinear neurons.

PMID- 12060707
TI  - Two rhodopsins mediate phototaxis to low- and high-intensity light in
      Chlamydomonas reinhardtii.
AB  - We demonstrate that two rhodopsins, identified from cDNA sequences, function as
      low- and high-light-intensity phototaxis receptors in the eukaryotic alga
      Chlamydomonas reinhardtii. Each of the receptors consists of an approximately 300
      residue seven-transmembrane helix domain with a retinal-binding pocket homologous
      to that of archaeal rhodopsins, followed by approximately 400 residues of
      additional membrane-associated portion. The function of the two rhodopsins,
      Chlamydomonas sensory rhodopsins A and B (CSRA and CSRB), as phototaxis receptors
      is demonstrated by in vivo analysis of photoreceptor electrical currents and
      motility responses in transformants with RNA interference (RNAi) directed against
      each of the rhodopsin genes. The kinetics, fluence dependencies, and action
      spectra of the photoreceptor currents differ greatly in transformants in accord
      with the relative amounts of photoreceptor pigments expressed. The data show that
      CSRA has an absorption maximum near 510 nm and mediates a fast photoreceptor
      current that saturates at high light intensity. In contrast, CSRB absorbs
      maximally at 470 nm and generates a slow photoreceptor current saturating at low
      light intensity. The relative wavelength dependence of CSRA and CSRB activity in
      producing phototaxis responses matches precisely the wavelength dependence of the
      CSRA- and CSRB-generated currents, demonstrating that each receptor mediates
      phototaxis. The saturation of the two photoreceptor currents at different light
      fluence levels extends the range of light intensity to which the organism can
      respond. Further, at intensities where both operate, their light signals are
      integrated at the level of membrane depolarization caused by the two
      photoreceptor currents.

PMID- 12060708
TI  - A role for ASIC3 in the modulation of high-intensity pain stimuli.
AB  - Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of the
      degenerins/epithelial sodium channel (DEG/ENaC) receptor family is expressed
      predominantly in sensory neurons including nociceptive neurons responding to
      protons. To study the role of ASIC3 in pain signaling, we generated ASIC3
      knockout mice. Mutant animals were healthy and responded normally to most sensory
      stimuli. However, in behavioral assays for pain responses, ASIC3 null mutant mice
      displayed a reduced latency to the onset of pain responses, or more pain-related
      behaviors, when stimuli of moderate to high intensity were used. This unexpected
      effect seemed independent of the modality of the stimulus and was observed in the
      acetic acid-induced writhing test (0.6 vs. 0.1-0.5%), in the hot-plate test (52.5
      and 55 vs. 50 degrees C), and in tests for mechanically induced pain (tail-pinch
      vs. von Frey filaments). We postulate that ASIC3 is involved in modulating
      moderate- to high-intensity pain sensation.

PMID- 12060709
TI  - Role of Lkb1, the causative gene of Peutz-Jegher's syndrome, in embryogenesis and
      polyposis.
AB  - Peutz-Jeghers syndrome (PJS) is a dominantly inherited human disorder
      characterized by gastrointestinal hamartomatous polyposis and mucocutaneous
      melanin pigmentation. LKB1 (STK11) serine/threonine kinase is the product of the
      causative gene of PJS, which has been mapped to chromosome 19p13.3. However,
      several studies have produced results that are not consistent with a link between
      LKB1 gene mutation and PJS. We constructed a knockout gene mutation of Lkb1 to
      determine whether it is the causative gene of PJS and to examine the biological
      role of the Lkb1 gene. Lkb1(-/-) mice died in utero between 8.5 and 9.5 days
      postcoitum. At 9.0 days postcoitum, Lkb1(-/-) embryos were generally smaller than
      their age-matched littermates, showed developmental retardation, and did not
      undergo embryonic turning. Multiple gastric adenomatous polyps were observed in
      10- to 14-month-old Lkb1(+/-) mice. Our results indicate that functional Lkb1 is
      required for normal embryogenesis and that it is related to tumor development.
      The Lkb1(+/-) mouse is suitable for studying molecular mechanism underlying the
      development of inherited gastric tumors in PJS.

PMID- 12060710
TI  - Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic
      expression of sonic hedgehog and bmp2b or exposure to cyclopamine.
AB  - Amputation of the zebrafish caudal fin stimulates regeneration of the dermal
      skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes.
      Expression patterns suggest a role for shh signaling in the secretion and
      patterning of the regenerating dermal bone, but a direct role has not been
      demonstrated. We established an in vivo method of gene transfection to express
      ectopically genes in the blastema of regenerating fins. Ectopic expression of shh
      or bmp2 in the blastema-induced excess bone deposition and altered patterning of
      the regenerate. The effects of shh ectopic expression could be antagonized by
      ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp)
      signaling. We disrupted shh signaling in the regenerating fin by exposure to
      cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation
      of melanocytes in the distal region of each fin ray, loss of actinotrichia, and
      reduction in cell proliferation in the mesenchyme. Morphological changes were
      accompanied by an expansion, followed by a reduction, in domains of shh
      expression and a rapid abolition of ptc1 expression. These results implicate shh
      and bmp2b signaling in the proliferation and/or differentiation of specialized
      bone-secreting cells in the blastema and suggest shh expression may be controlled
      by regulatory feedback mechanisms that define the region of bone secretion in the
      outgrowing fin.

PMID- 12060711
TI  - Tuning the membrane surface potential for efficient toxin import.
AB  - Membrane surface electrostatic interactions impose structural constraints on
      imported proteins. An unprecedented sensitive dependence on these constraints was
      seen in the voltage-gated import and channel formation by the C-terminal pore
      forming domain of the bacteriocin, colicin E1. At physiological ionic strengths,
      significant channel current was observed only in a narrow interval of anionic
      lipid content ([L-]), with the maximum current (I(max)) at 25-30 mol% (dioleoyl)
      phosphatidylglycerol ([L-]max) corresponding to a surface potential of the lipid
      bilayer in the absence of protein, psi(o)max = -60 +/- 5 mV. Higher ionic
      strength shifted [L-]max to larger values, but psi(o)max remained approximately
      constant. It is proposed that the channel current (i) increases and (ii)
      decreases at /psi(o)/ values <55 mV and >65 mV, because of (i) electrostatic
      interactions needed for effective insertion of the channel polypeptide and (ii)
      constraints due to electrostatic forces on the flexibility needed for cooperative
      insertion into the membrane. The loss of flexibility for /psi(o)/ 65 mV was
      demonstrated by the absence of thermally induced intraprotein distance changes of
      the bound polypeptide. The anionic lipid content, 25-30 mol%, corresponding to
      the channel current maxima, is similar to that of the target Escherichia coli
      cytoplasmic membrane and membranes of mesophilic microorganisms. This suggests
      that one reason the membrane surface potential is tuned in vivo is to facilitate
      protein import.

PMID- 12060712
TI  - C75 increases peripheral energy utilization and fatty acid oxidation in diet
      induced obesity.
AB  - C75, a known inhibitor of fatty acid synthase is postulated to cause significant
      weight loss through decreased hypothalamic neuropeptide Y (NPY) production.
      Peripherally, C75, an alpha-methylene-gamma-butyrolactone, reduces adipose tissue
      and fatty liver, despite high levels of malonyl-CoA. To investigate this paradox,
      we studied the effect of C75 on fatty acid oxidation and energy production in
      diet-induced obese (DIO) mice and cellular models. Whole-animal calorimetry
      showed that C75-treated DIO mice had a 50% greater weight loss, and a 32.9%
      increased production of energy because of fatty acid oxidation, compared with
      paired-fed controls. Etomoxir, an inhibitor of carnitine O-palmitoyltransferase-1
      (CPT-1), reversed the increased energy expenditure in DIO mice by inhibiting
      fatty acid oxidation. C75 treatment of rodent adipocytes and hepatocytes and
      human breast cancer cells increased fatty acid oxidation and ATP levels by
      increasing CPT-1 activity, even in the presence of elevated concentrations of
      malonyl-CoA. Studies in human cancer cells showed that C75 competed with malonyl
      CoA, as measured by CPT-1 activity assays. Thus, C75 acts both centrally to
      reduce food intake and peripherally to increase fatty acid oxidation, leading to
      rapid and profound weight loss, loss of adipose mass, and resolution of fatty
      liver. The pharmacological stimulation of CPT-1 activity is a novel finding. The
      dual action of the C75 class of compounds as fatty acid synthase inhibitors and
      CPT-1 agonists has therapeutic implications in the treatment of obesity and type
      II diabetes.

PMID- 12060713
TI  - Local circuit neurons in the striatum regulate neural and behavioral responses to
      dopaminergic stimulation.
AB  - Interneurons are critical for shaping neuronal circuit activity in many parts of
      the central nervous system. To study interneuron function in the basal ganglia,
      we tested and characterized an NK-1 receptor-based method for targeted ablation
      of specific classes of interneuron in the striatum. Our findings demonstrate that
      the neurotoxin SP-PE35, a substance P-Pseudomonas exotoxin conjugate, selectively
      targets striatal cholinergic and nitric oxide synthase/somatostatinergic
      interneurons when injected locally into the striatum. The effects of this
      selective cell targeting encompassed alterations in both behavioral and neural
      responses to dopaminergic stimulation, including altered patterns of early-gene
      response in striosomes and matrix. We conclude that NK-1-bearing local circuit
      neurons of the striatum regulate the differential responses of striatal
      projection neurons to dopamine-mediated signaling.

PMID- 12060714
TI  - Evidence that subcellular localization of a bacterial membrane protein is
      achieved by diffusion and capture.
AB  - Bacteria lack an endoplasmic reticulum, a Golgi apparatus, and transport vesicles
      and yet are capable of sorting and delivering integral membrane proteins to
      particular sites within the cell with high precision. What is the pathway by
      which membrane proteins reach their proper subcellular destination in bacteria?
      We have addressed this question by using green fluorescent protein (GFP) fused to
      a polytopic membrane protein (SpoIVFB) that is involved in the process of
      sporulation in the bacterium Bacillus subtilis. SpoIVFB-GFP localizes to a region
      of the sporulating cell known as the outer forespore membrane, which is distinct
      from the cytoplasmic membrane. Experiments are presented that rule out a
      mechanism in which SpoIVFB-GFP localizes to all membranes but is selectively
      eliminated from the cytoplasmic membrane by proteolytic degradation and argue
      against a model in which SpoIVFB-GFP is selectively inserted into the outer
      forespore membrane. Instead, the results are most easily compatible with a model
      in which SpoIVFB-GFP achieves proper localization by insertion into the
      cytoplasmic membrane followed by diffusion to, and capture in, the outer
      forespore membrane. The possibility that diffusion and capture is a general
      feature of protein localization in bacteria is discussed.

PMID- 12060715
TI  - Intraspecific violation of genetic colinearity and its implications in maize.
AB  - Although allelic sequences can vary extensively, it is generally assumed that
      each gene in one individual will have an allelic counterpart in another
      individual of the same species. We report here that this assumption does not hold
      true in maize. We have sequenced over 100 kb from the bz genomic region of two
      different maize lines and have found dramatic differences between them. First,
      the retrotransposon clusters, which comprise most of the repetitive DNA in maize,
      differ markedly in make-up and location relative to the genes in the bz region.
      Second, and more importantly, the genes themselves differ between the two lines,
      demonstrating that genetic microcolinearity can be violated within the same
      species. Our finding has bearing on the underlying genetic basis of hybrid vigor
      in maize, and possibly other organisms, and on the measurement of genetic
      distances.

PMID- 12060716
TI  - Amyotrophic lateral sclerosis: a proposed mechanism.
AB  - Missense mutations in Cu,Zn-superoxide dismutase (SOD1) account for approximately
      20% of familial amyotrophic lateral sclerosis (FALS) through some, as yet
      undefined, toxic gain of function that leads to gradual death of motor neurons.
      Mitochondrial swelling and vacuolization are early signs of incipient motor
      neuron death in FALS. We previously reported that SOD1 exists in the
      intermembrane space of mitochondria. Herein, we demonstrate that the entry of
      SOD1 into mitochondria depends on demetallation and that heat shock proteins
      (Hsp70, Hsp27, or Hsp25) block the uptake of the FALS-associated mutant SOD1
      (G37R, G41D, or G93A), while having no effect on wild-type SOD1. The binding of
      mutant SOD1 to Hsps in the extract of neuroblastoma cells leads to formation of
      sedimentable aggregates. Many antiapoptotic effects of Hsps have been reported.
      We now propose that this binding of Hsps to mutant forms of a protein abundant in
      motor neurons, such as SOD1, makes Hsps unavailable for their antiapoptotic
      functions and leads ultimately to motor neuron death. It also appears that the
      Hsp-SOD1 complex recruits other proteins present in the neuroblastoma cell and
      presumably in motor neurons to form sedimentable aggregates.

PMID- 12060717
TI  - The systemin receptor SR160 from Lycopersicon peruvianum is a member of the LRR
      receptor kinase family.
AB  - The isolation to homogeneity of the 160-kDa systemin cell-surface receptor
      (SR160) from plasma membranes of suspension cultured cells of Lycopersicon
      peruvianum is reported. The purification procedure resulted in recovery of 13
      microg of pure receptor protein, representing an 8,200-fold purification. Gel
      blot analyses using SR160-specific antibodies confirmed that a cross-reacting
      protein in the membranes of suspension-cultured cells comigrates with both the
      native and a deglycosylated form of the radiolabeled receptor. Internal amino
      acid sequences of the purified protein facilitated the isolation of a cDNA clone
      encoding the 160-kDa receptor. The identity of the encoded protein as SR160 was
      further confirmed by a comparison of its sequence with a mass spectral
      fingerprint of the SR160 protein. The deduced amino acid sequence of SR160
      revealed that it is a member of the leucine-rich repeat (LRR) receptor kinase
      family, closely related to the brassinolide receptor kinase, BRI1.

PMID- 12060718
TI  - Intestinal adenomas can develop with a stable karyotype and stable
      microsatellites.
AB  - Loss of function of the adenomatous polyposis coli (APC)/Apc tumor suppressor
      gene occurs early in the etiology of intestinal cancer in mammals. In human
      colonic tumors, genomic instability is proposed to be associated with tumor
      initiation by inducing loss of APC function. We have used a mouse model of
      inherited intestinal cancer (Apc(Min)/+, Min/+) to analyze the earliest stages of
      tumorigenesis in this organ. We find that tumors from C57BL/6 Min/+ mice have a
      stable karyotype and stable microsatellites. In contrast to previous claims, we
      find that homozygosity for the Min allele of Apc in tumors can proceed by
      homologous somatic recombination. Further, our analysis of early, benign human
      colorectal adenomas failed to reveal any evidence for generalized chromosomal or
      microsatellite instability. These results cast doubt on the hypothesis that
      either of these forms of genomic instability is necessary for the initial
      development of colorectal adenomas. We contrast our analysis of autochthonous
      primary tumors to other studies involving xenografts or cultured cells.

PMID- 12060719
TI  - Short inverted repeats initiate gene amplification through the formation of a
      large DNA palindrome in mammalian cells.
AB  - Gene amplification is a common form of genomic instability in a wide variety of
      organisms and is often associated with tumor progression in mammals. One striking
      feature of many amplified genes is their organization as large inverted
      duplications (palindromes). Here, we describe a molecular mechanism for
      palindrome formation in mammalian cells that is also conserved in protists. We
      introduced a short (79 or 229 bp) inverted repeat into the genome of Chinese
      hamster ovary cells and showed that it promoted the formation of a large DNA
      palindrome after an adjacent DNA double-strand break. This finding suggests that
      short inverted repeats in the mammalian genome can have a critical role in the
      initiation of gene amplification. This specific mechanism may provide a novel
      target for cancer therapies.

PMID- 12060720
TI  - NTP-sensing by rRNA promoters in Escherichia coli is direct.
AB  - We showed previously that rrn P1 promoters require unusually high concentrations
      of the initiating nucleoside triphosphates (ATP or GTP, depending on the
      promoter) for maximal transcription in vitro. We proposed that this requirement
      for high initiating NTP concentrations contributes to control of the rrn P1
      promoters from the seven Escherichia coli rRNA operons. However, the previous
      studies did not prove that variation in NTP concentration affects rrn P1 promoter
      activity directly in vivo. Here, we create conditions in vivo in which ATP and
      GTP concentrations are altered in opposite directions relative to one another,
      and we show that transcription from rrn P1 promoters that initiate with either
      ATP or GTP follows the concentration of the initiating NTP for that promoter.
      These results demonstrate that the effect of initiating NTP concentration on rrn
      P1 promoter activity in vivo is direct. As predicted by a model in which
      homeostatic control of rRNA transcription results, at least in part, from sensing
      of NTP concentrations by rrn P1 promoters, we show that inhibition of protein
      synthesis results in an increase in ATP concentration and a corresponding
      increase in transcription from rrnB P1. We conclude that translation is a major
      consumer of purine NTPs, and that NTP-sensing by rrn P1 promoters serves as a
      direct regulatory link between translation and ribosome synthesis.

PMID- 12060721
TI  - DNA containing CpG motifs induces angiogenesis.
AB  - New blood vessel formation in the cornea is an essential step in the pathogenesis
      of a blinding immunoinflammatory reaction caused by ocular infection with herpes
      simplex virus (HSV). By using a murine corneal micropocket assay, we found that
      HSV DNA (which contains a significant excess of potentially bioactive "CpG"
      motifs when compared with mammalian DNA) induces angiogenesis. Moreover,
      synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells
      and stimulate the release of vascular endothelial growth factor (VEGF), which in
      turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1
      murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was
      blocked by the administration of anti-mVEGF Ab or the inclusion of "neutralizing"
      oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG
      DNA. These findings establish that DNA containing bioactive CpG motifs induces
      angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the
      blinding lesions of stromal keratitis.

PMID- 12060722
TI  - TRAF6-deficient mice display hypohidrotic ectodermal dysplasia.
AB  - Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter
      protein that links signals from members of the TNFR superfamily and Toll/IL-1
      receptor family to activation of transcription factors NFkappaB and AP-1.
      Analysis of TRAF6-deficient mice revealed that TRAF6 is essential for normal bone
      formation and establishment of immune and inflammatory systems. Here we report
      that TRAF6 deficiency results in defective development of epidermal appendixes,
      including guard hair follicles, sweat glands, sebaceous glands of back skin, and
      modified sebaceous glands such as meibomian glands, anal glands, and preputial
      glands. Except the sebaceous gland impairment, these abnormal phenotypes are
      identical to those observed in Tabby (Ta), downless (dl), and crinkled (cr) mice,
      which are models of hypohidrotic (anhidrotic) ectodermal dysplasia in human. beta
      catenin and mucosal addressin cell adhesion molecule-1, an early marker of
      developing guard-hair follicles is absent in the skin of TRAF6-deficient embryos.
      Thus, TRAF6 is essential for development of epidermal appendixes. TRAF6 does not
      associate with the cytoplasmic tail of the dl protein (DL)/ectodysplasin receptor
      (EDAR) receptor, which, when mutated, results in hypohidrotic (anhidrotic)
      ectodermal dysplasia. However, TRAF6 associates with X-linked ectodysplasin-A2
      receptor (XEDAR) and TNFR super family expressed on the mouse embryo
      (TROY/toxicity and JNK inducer (TAJ), which are EDAR-related members of the TNFR
      superfamily that are expressed at high level in epidermal appendixes.
      Furthermore, TRAF6 is essential for the XEDAR-mediated NFkappaB activation. Our
      results suggest that TRAF6 may transduce signals emanating from XEDAR or TROY/TAJ
      that are associated with development of epidermal appendixes.

PMID- 12060723
TI  - Ganglioside rafts as MAG receptors that mediate blockade of axon growth.

PMID- 12060724
TI  - Chasing "fear memories" to the cerebellum.

PMID- 12060725
TI  - After 130 years, the molecular mechanism of action of nitroglycerin is revealed.

PMID- 12060726
TI  - Founder effects and silvereyes.

PMID- 12060727
TI  - Community structure in social and biological networks.
AB  - A number of recent studies have focused on the statistical properties of
      networked systems such as social networks and the Worldwide Web. Researchers have
      concentrated particularly on a few properties that seem to be common to many
      networks: the small-world property, power-law degree distributions, and network
      transitivity. In this article, we highlight another property that is found in
      many networks, the property of community structure, in which network nodes are
      joined together in tightly knit groups, between which there are only looser
      connections. We propose a method for detecting such communities, built around the
      idea of using centrality indices to find community boundaries. We test our method
      on computer-generated and real-world graphs whose community structure is already
      known and find that the method detects this known structure with high sensitivity
      and reliability. We also apply the method to two networks whose community
      structure is not well known--a collaboration network and a food web--and find
      that it detects significant and informative community divisions in both cases.

PMID- 12060728
TI  - Electrolytic actuators: alternative, high-performance, material-based devices.
AB  - The emerging field of materials-based actuation continues to be the focus of
      considerable research because of its inherent scalability and its promise to
      drive micromechanical devices that cannot be realized with conventional
      mechanical actuator strategies. The electrolytic phase transformation actuator
      offers a new broad-spectrum solution to the problem of direct conversion of
      electrical to mechanical energy. Strains of 136,000% and unoptimized work cycle
      efficiencies near 50% are demonstrated in a prototype device. Conceivably capable
      of generating stress beyond 200 MPa, this new approach promises performance
      orders of magnitude beyond other novel actuation strategies.

PMID- 12060729
TI  - An atmospheric pCO2 reconstruction across the Cretaceous-Tertiary boundary from
      leaf megafossils.
AB  - The end-Cretaceous mass extinctions, 65 million years ago, profoundly influenced
      the course of biotic evolution. These extinctions coincided with a major
      extraterrestrial impact event and massive volcanism in India. Determining the
      relative importance of each event as a driver of environmental and biotic change
      across the Cretaceous-Tertiary boundary (KTB) crucially depends on constraining
      the mass of CO(2) injected into the atmospheric carbon reservoir. Using the
      inverse relationship between atmospheric CO(2) and the stomatal index of land
      plant leaves, we reconstruct Late Cretaceous-Early Tertiary atmospheric CO(2)
      concentration (pCO(2)) levels with special emphasis on providing a pCO(2)
      estimate directly above the KTB. Our record shows stable Late Cretaceous/Early
      Tertiary background pCO(2) levels of 350-500 ppm by volume, but with a marked
      increase to at least 2,300 ppm by volume within 10,000 years of the KTB.
      Numerical simulations with a global biogeochemical carbon cycle model indicate
      that CO(2) outgassing during the eruption of the Deccan Trap basalts fails to
      fully account for the inferred pCO(2) increase. Instead, we calculate that the
      postboundary pCO(2) rise is most consistent with the instantaneous transfer of
      approximately 4,600 Gt C from the lithic to the atmospheric reservoir by a large
      extraterrestrial bolide impact. A resultant climatic forcing of +12 W.m(-2) would
      have been sufficient to warm the Earth's surface by approximately 7.5 degrees C,
      in the absence of counter forcing by sulfate aerosols. This finding reinforces
      previous evidence for major climatic warming after the KTB impact and implies
      that severe and abrupt global warming during the earliest Paleocene was an
      important factor in biotic extinction at the KTB.

PMID- 12060730
TI  - Latitudinal difference in biodiversity caused by higher tropical rate of
      increase.
AB  - Tropical diversity has generally exceeded temperate diversity in the present and
      at points in the past, but whether measured differences have remained relatively
      constant through time has been unknown. Here we examine tropical vs. temperate
      diversities from the Neogene to Recent using the within-habitat diversity measure
      Fisher's alpha of Cenozoic benthic foraminifera from the temperate Central
      Atlantic Coastal Plain and the tropical Central American Isthmus. During the
      Neogene, the mean value of alpha at temperate latitudes increased 1.4 times or
      40%, whereas in the tropics it increased 2.1 times or 106%. Thus, while both
      areas exhibit an increase of diversity with time, past differences in the rate of
      increase have generated a more pronounced gradient today (164%) than existed in
      the Miocene (80%). These data disagree with the suggestion that the world reached
      an equilibrium number of species during the Paleozoic and demonstrate the need to
      consider both temperate and tropical components in global diversity assessments.

PMID- 12060731
TI  - Temperature profile for glacial ice at the South Pole: implications for life in a
      nearby subglacial lake.
AB  - Airborne radar has detected approximately 100 lakes under the Antarctic ice cap,
      the largest of which is Lake Vostok. International planning is underway to search
      in Lake Vostok for microbial life that may have evolved in isolation from surface
      life for millions of years. It is thought, however, that the lakes may be
      hydraulically interconnected. If so, unsterile drilling would contaminate not
      just one but many of them. Here we report measurements of temperature vs. depth
      down to 2,345 m in ice at the South Pole, within 10 km from a subglacial lake
      seen by airborne radar profiling. We infer a temperature at the 2,810-m deep base
      of the South Pole ice and at the lake of -9 degrees C, which is 7 degrees C below
      the pressure-induced melting temperature of freshwater ice. To produce the strong
      radar signal, the frozen lake must consist of a mix of sediment and ice in a flat
      bed, formed before permanent Antarctic glaciation. It may, like Siberian and
      Antarctic permafrost, be rich in microbial life. Because of its hydraulic
      isolation, proximity to South Pole Station infrastructure, and analog to a
      Martian polar cap, it is an ideal place to test a sterile drill before risking
      contamination of Lake Vostok. From the semiempirical expression for strain rate
      vs. shear stress, we estimate shear vs. depth and show that the IceCube neutrino
      observatory will be able to map the three-dimensional ice-flow field within a
      larger volume (0.5 km(3)) and at lower temperatures (-20 degrees C to -35 degrees
      C) than has heretofore been possible.

PMID- 12060732
TI  - A framework for sustainability science: a renovated IPAT identity.
AB  - Learning actors' leverage for change along the journey to sustainability requires
      quantifying the component forces of environmental impact and integrating them.
      Population, income, consumers' behavior, and producers' efficiency jointly force
      impact. Here, we renovate the "IPAT Identity" to identify actors with the forces.
      Forcing impact I are P for population, A for income as gross domestic product
      (GDP) per capita, C for intensity of use as a good per GDP, and T for efficiency
      ratios as impact per good. In the "ImPACT Identity," parents modify P, workers
      modify A, consumers modify C, and producers modify T. Because annual percentage
      changes in component forces add to a change in national impact, actors' leverage
      is reflected transparently in consistent units of annual percentage changes that
      can be compared from force to force. Examples from energy and food, farming and
      manufacturing, and steel and water show that declining C, called
      dematerialization, can temper the sustainability challenge of growth (P x A), and
      that innovation or efficient technology that lowers T can counter rising
      consumption (P x A x C). Income elasticity can accommodate connections between
      income and other forces. From rates of change of forces, the identity can
      forecast impacts. Alternatively, by identifying the necessary change in forces to
      cause a projected impact, ImPACT can assay the likelihood and practicability of
      environmental targets and timetables. An annual 2-3% progress in consumption and
      technology over many decades and sectors provides a benchmark for sustainability.

PMID- 12060733
TI  - In vitro and in vivo studies of a VEGF121/rGelonin chimeric fusion toxin
      targeting the neovasculature of solid tumors.
AB  - Vascular endothelial growth factor (VEGF) plays a key role in the growth and
      metastasis of solid tumors. We generated a fusion protein containing VEGF(121)
      linked by a flexible G(4)S tether to the toxin gelonin (rGel) and expressed this
      as a soluble protein in bacteria. Purified VEGF(121)/rGel migrated as an 84-kDa
      homodimer under nonreducing conditions. VEGF(121)/rGel bound to purified,
      immobilized Flk-1, and the binding was competed by VEGF(121). Both VEGF(121)/rGel
      and VEGF(121) stimulated cellular kinase insert domain receptor (KDR)
      phosphorylation. The VEGF(121)/rGel fusion construct was highly cytotoxic to
      endothelial cells overexpressing the KDR/Flk-1 receptor. The IC(50) of the
      construct on dividing endothelial cells expressing 10(5) or more KDR/Flk-1
      receptors per cell was 0.5-1 nM, as compared with 300 nM for rGel itself.
      Dividing endothelial cells overexpressing KDR were approximately 60-fold more
      sensitive to VEGF(121)/rGel than were nondividing cells. Endothelial cells
      overexpressing FLT-1 were not sensitive to the fusion protein. Human melanoma (A
      375) or human prostate (PC-3) xenografts treated with the fusion construct
      demonstrated a reduction in tumor volume to 16% of untreated controls. The fusion
      construct localized selectively to PC-3 tumor vessels and caused thrombotic
      damage to tumor vessels with extravasation of red blood cells into the tumor bed.
      These studies demonstrate the successful use of VEGF(121)/rGel fusion construct
      for the targeted destruction of tumor vasculature in vivo.

PMID- 12060734
TI  - In vitro formation of a c-type cytochrome.
AB  - C-type cytochromes are essential for almost all organisms; they are characterized
      by the covalent attachment of heme to protein through two thioether bonds to a
      Cys-Xaa-Xaa-Cys-His peptide motif. Here we show, contrary to opinion of 30 years
      standing, that a c-type cytochrome can form from heme and apoprotein in vitro
      under mild conditions and in the absence of any biosynthesis apparatus. This
      reaction occurs provided formation of a disulfide bond within the Cys-Xaa-Xaa-Cys
      His motif is avoided. There are important implications for understanding in vivo
      cytochrome c assembly.

PMID- 12060735
TI  - A monomeric red fluorescent protein.
AB  - All coelenterate fluorescent proteins cloned to date display some form of
      quaternary structure, including the weak tendency of Aequorea green fluorescent
      protein (GFP) to dimerize, the obligate dimerization of Renilla GFP, and the
      obligate tetramerization of the red fluorescent protein from Discosoma (DsRed).
      Although the weak dimerization of Aequorea GFP has not impeded its acceptance as
      an indispensable tool of cell biology, the obligate tetramerization of DsRed has
      greatly hindered its use as a genetically encoded fusion tag. We present here the
      stepwise evolution of DsRed to a dimer and then either to a genetic fusion of two
      copies of the protein, i.e., a tandem dimer, or to a true monomer designated
      mRFP1 (monomeric red fluorescent protein). Each subunit interface was disrupted
      by insertion of arginines, which initially crippled the resulting protein, but
      red fluorescence could be rescued by random and directed mutagenesis totaling 17
      substitutions in the dimer and 33 in mRFP1. Fusions of the gap junction protein
      connexin43 to mRFP1 formed fully functional junctions, whereas analogous fusions
      to the tetramer and dimer failed. Although mRFP1 has somewhat lower extinction
      coefficient, quantum yield, and photostability than DsRed, mRFP1 matures >10
      times faster, so that it shows similar brightness in living cells. In addition,
      the excitation and emission peaks of mRFP1, 584 and 607 nm, are approximately 25
      nm red-shifted from DsRed, which should confer greater tissue penetration and
      spectral separation from autofluorescence and other fluorescent proteins.

PMID- 12060736
TI  - Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes
      simplex virus-1-infected cell protein 0.
AB  - Infected cell protein 0 (ICP0) of herpes simplex virus-1 is a 775-aa residue
      multifunctional protein that acts as a promiscuous transactivator linked to the
      degradation of several proteins. ICP0 is the only protein known which encodes two
      physically separated E3 ubiquitin (Ub) ligase domains, one, designated herpes
      virus Ub ligase 1 (HUL-1) located in a domain encoded in exon 3 and one
      designated herpes virus Ub ligase 2 (HUL-2) associated with the really
      interesting new gene (RING) finger domain encoded by exon 2. We report the
      following: (i) ICP0 residues 543-680 are sufficient for HUL-1 E3 activity and
      necessary determinants are encoded between residues 616 and 680. (ii) In
      substrate independent in vitro ubiquitylation reactions, a chimeric protein
      containing the HUL-1 domain promotes the ubiquitylation of itself and the
      ubiquitin conjugating enzyme (E2) cdc34 and interacts with cdc34. (iii) The
      mechanism of HUL-1 E3 function does not involve formation of a thioester between
      the HUL-1 domain and Ub. (iv) Residues 621-625 are essential for in vitro HUL-1
      E3 activity and interaction between the HUL-1 domain and cdc34, suggesting that
      this interaction is required for HUL-1 E3 function.

PMID- 12060737
TI  - Domain movements in human fatty acid synthase by quantized elastic deformational
      model.
AB  - This paper reports the results of applying a computational method called the
      quantized elastic deformational model, to the determination of conformational
      flexibility of the supermolecular complex of human fatty acid synthase. The
      essence of this method is the ability to model large-scale conformational changes
      such as domain movements by treating the protein as an elastic object without the
      knowledge of protein primary sequence and atomic coordinates. The calculation was
      based on the electron density maps of the synthase at 19 A. The results suggest
      that the synthase is a very flexible molecule. Two types of flexible hinges in
      the structure were identified. One is an intersubunit hinge formed by the
      intersubunit connection and the other is an intrasubunit hinge located between
      domains I and II. Despite the fact that the dimeric synthase has a chemically
      symmetric structure, large domain movements around the hinge region occur in
      various directions and allow the molecule to adopt a wide range of conformations.
      These domain movements are likely to be important in facilitating and regulating
      the entire palmitate synthesis by coordinating the communication between
      components of the molecule, for instance, adjusting the distance between various
      active sites inside the catalytic reaction center. Finally, the ability to
      describe protein motions of a supermolecular complex, without the information of
      protein sequence and atomic coordinates, is a major advance in computational
      modeling of protein dynamics. The method provides an unprecedented ability to
      model protein motions at such a low resolution of structure.

PMID- 12060739
TI  - p38 is essential for the assembly and stability of macromolecular tRNA synthetase
      complex: implications for its physiological significance.
AB  - Mammalian tRNA synthetases form a macromolecular complex with three nonenzyme
      factors: p43, p38, and p18. Here we introduced a mutation within the mouse p38
      gene to understand its functional significance for the formation of the multi
      tRNA synthetase complex. The complex was completely disintegrated by the
      deficiency of p38. In addition, the protein levels and catalytic activities of
      the component enzymes and cofactors were severely decreased. A partial truncation
      of the p38 polypeptide separated the associated components into different
      subdomains. The mutant mice showed lethality within 2 days of birth. Thus, this
      work provides the first evidence, to our knowledge, that p38 is essential for the
      structural integrity of the multi-tRNA synthetase complex and mouse viability.

PMID- 12060738
TI  - Shotgun identification of protein modifications from protein complexes and lens
      tissue.
AB  - Large-scale genomics has enabled proteomics by creating sequence infrastructures
      that can be used with mass spectrometry data to identify proteins. Although
      protein sequences can be deduced from nucleotide sequences, posttranslational
      modifications to proteins, in general, cannot. We describe a process for the
      analysis of posttranslational modifications that is simple, robust, general, and
      can be applied to complicated protein mixtures. A protein or protein mixture is
      digested by using three different enzymes: one that cleaves in a site-specific
      manner and two others that cleave nonspecifically. The mixture of peptides is
      separated by multidimensional liquid chromatography and analyzed by a tandem mass
      spectrometer. This approach has been applied to modification analyses of proteins
      in a simple protein mixture, Cdc2p protein complexes isolated through the use of
      an affinity tag, and lens tissue from a patient with congenital cataracts.
      Phosphorylation sites have been detected with known stoichiometry of as low as
      10%. Eighteen sites of four different types of modification have been detected on
      three of the five proteins in a simple mixture, three of which were previously
      unreported. Three proteins from Cdc2p isolated complexes yielded eight sites
      containing three different types of modifications. In the lens tissue, 270
      proteins were identified, and 11 different crystallins were found to contain a
      total of 73 sites of modification. Modifications identified in the crystallin
      proteins included Ser, Thr, and Tyr phosphorylation, Arg and Lys methylation, Lys
      acetylation, and Met, Tyr, and Trp oxidations. The method presented will be
      useful in discovering co- and posttranslational modifications of proteins.

PMID- 12060740
TI  - A theoretical examination of the factors controlling the catalytic efficiency of
      the DNA-(adenine-N6)-methyltransferase from Thermus aquaticus.
AB  - Ab initio and density functional calculations have been carried out to more fully
      understand the factors controlling the catalytic activity of the Thermus
      aquaticus DNA methyltransferase (MTaqI) in the N-methylation at the N(6) of an
      adenine nucleobase. The noncatalyzed reaction was modeled as a methyl transfer
      from trimethylsulfonium to the N(6) of adenine. Activation barriers of 32.0
      kcal/mol and 24.0 kcal/mol were predicted for the noncatalyzed reaction in the
      gas phase by MP2/6-31+G(d,p)//HF/6-31+G(d,p) and B3LYP/6-31+G(d,p) calculations,
      respectively. Calculations performed to evaluate the effect of substrate
      positioning in the active site of MTaqI on the reaction determine the barrier to
      be 23.4 kcal/mol and 17.3 kcal/mol for the MP2/6-31+G(d,p)//HF/6-31+G(d,p) and
      B3LYP/6-31+G(d,p) gas phase calculations, respectively. The effect of hydrogen
      bonding between the N(6) of adenine and the terminal oxygen of Asn-105 on the
      activation barrier was also studied. A formamide molecule was modeled into the
      system to mimic the function of active site residue Asn-105. The activation
      barrier for this reaction was found to be 21.8 kcal/mol and 15.8 kcal/mol as
      determined from the MP2/6-31+G(d,p)//HF/6-31+G(d,p) and B3LYP/6-31+G(d,p)
      calculations, respectively. This result predicts a contribution of less than 2
      kcal/mol to the lowering of the activation barrier from amide hydrogen bonding
      between formamide and N(6) of adenine. Comparison of the reaction coordinates
      suggest that it is not the hydrogen bonding of the Asn-105 that lends to the
      catalytic prowess of the enzyme since the organization of the substrates in the
      active site of the enzyme has a far greater effect on reducing the activation
      barrier. The results also suggest a stepwise mechanism for the removal of the
      hydrogen from the N(6) of adenine as opposed to a concerted reaction in which a
      proton is abstracted simultaneously with the transfer of the methyl group. The
      hydrogen on the N(6) of the intermediate methyl adenine product is far more
      acidic than in the reactant complex and may be subsequently abstracted by basic
      groups in the active site that are too weak to abstract the proton before the
      full sp(3) hybridization of the attacking nitrogen.

PMID- 12060741
TI  - HIV type 1 Gag virus-like particle budding from spheroplasts of Saccharomyces
      cerevisiae.
AB  - Expression of retroviral Gag protein in yeast has previously shown Gag targeting
      to the plasma membrane but little or no production of Gag virus-like particles
      (VLPs). Here we show that, after removal of the cell wall, the expression of HIV
      type 1 Gag protein in Saccharomyces cerevisiae spheroplasts allowed simultaneous
      budding of VLPs from the plasma membrane. Our data show that (i) the VLPs
      released from yeast spheroplasts were spherical and had morphological features,
      such as membrane apposed electron-dense layers, characteristic of the immature
      form of HIV particles; (ii) the VLPs were completely enclosed in the plasma
      membrane derived from yeast, which is denser than that of higher eukaryotic
      cells; (iii) the VLP Gag shells remained intact after treatment of nonionic
      detergent; and (iv) the VLPs were released soon after removal of the cell wall
      and accumulated up to 300 microg/liter of culture. Our results also show that VLP
      production was abolished by amino acid substitution of the Gag N-terminal
      myristoylglycine and impaired when Gag C-terminal deletions were extended beyond
      the nucleocapsid domain. These results were consistent with those obtained
      previously in higher eukaryotic expression systems, suggesting that similar Gag
      domains were used for VLP assembly. We suggest that the system described here
      offers significant advantages for studying host factors required for VLP budding.
      The system also may be available for production of vector virus-free VLPs for
      practical applications such as vaccine development.

PMID- 12060742
TI  - Regulatory interaction of phosducin-like protein with the cytosolic chaperonin
      complex.
AB  - Phosducin and phosducin-like protein (PhLP) bind G protein betagamma subunits and
      regulate their activity. This report describes a previously uncharacterized
      binding partner unique to PhLP that was discovered by coimmunoprecipitation
      coupled with mass spectrometric identification. Chaperonin containing tailless
      complex polypeptide 1 (CCT), a cytosolic chaperone responsible for the folding of
      many cellular proteins, binds PhLP with a stoichiometry of one PhLP per CCT
      complex. Unlike protein-folding substrates of CCT, which interact only in their
      nonnative conformations, PhLP binds in its native state. Native PhLP competes
      directly for binding of protein substrates of CCT and thereby inhibits CCT
      activity. Overexpression of PhLP inhibited the ability of CCT to fold newly
      synthesized beta-actin by 80%. These results suggest that the interaction between
      PhLP and CCT may be a means to regulate CCT-dependent protein folding or
      alternatively, to control the availability of PhLP to modulate G protein
      signaling.

PMID- 12060743
TI  - The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin
      from Actinosynnema pretiosum.
AB  - Maytansinoids are potent antitumor agents found in plants and microorganisms. To
      elucidate their biosynthesis at the biochemical and genetic level and to set the
      stage for their structure modification through genetic engineering, we have
      cloned two gene clusters required for the biosynthesis of the maytansinoid,
      ansamitocin, from a cosmid library of Actinosynnema pretiosum ssp. auranticum
      ATCC 31565. This is a rare case in which the genes involved in the formation of a
      secondary metabolite are dispersed in separate regions in an Actinomycete. A set
      of genes, asm22-24, asm43-45, and asm47, was identified for the biosynthesis of
      the starter unit, 3-amino-5-hydroxybenzoic acid (AHBA). Remarkably, there are two
      AHBA synthase gene homologues, which may have different functions in AHBA
      formation. Four type I polyketide synthase genes, asmA-D, followed by the
      downloading asm9, together encode eight homologous sets of enzyme activities
      (modules), each catalyzing a specific round of chain initiation, elongation, or
      termination steps, which assemble the ansamitocin polyketide backbone. Another
      set of genes, asm13-17, encodes the formation of an unusual "methoxymalonate"
      polyketide chain extension unit that, notably, seems to be synthesized on a
      dedicated acyl carrier protein rather than as a CoA thioester. Additional ORFs
      are involved in postsynthetic modifications of the initial polyketide synthase
      product, which include methylations, an epoxidation, an aromatic chlorination,
      and the introduction of acyl and carbamoyl groups. Tentative functions of several
      asm genes were confirmed by inactivation and heterologous expression.

PMID- 12060744
TI  - Crystal structure of conserved hypothetical protein Aq1575 from Aquifex aeolicus.
AB  - The crystal structure of a conserved hypothetical protein, Aq1575, from Aquifex
      aeolicus has been determined by using x-ray crystallography. The protein belongs
      to the domain of unknown function DUF28 in the Pfam and PALI databases for which
      there was no structural information available until now. A structural homology
      search with the DALI algorithm indicates that this protein has a new fold with no
      obvious similarity to those of other proteins of known three-dimensional
      structure. The protein reveals a monomer consisting of three domains arranged
      along a pseudo threefold symmetry axis. There is a large cleft with approximate
      dimensions of 10 A x 10 A x 20 A in the center of the three domains along the
      symmetry axis. Two possible active sites are suggested based on the structure and
      multiple sequence alignment. There are several highly conserved residues in these
      putative active sites. The structure based molecular properties and
      thermostability of the protein are discussed.

PMID- 12060746
TI  - Ultrafast spectroscopy reveals subnanosecond peptide conformational dynamics and
      validates molecular dynamics simulation.
AB  - Femtosecond time-resolved spectroscopy on model peptides with built-in light
      switches combined with computer simulation of light-triggered motions offers an
      attractive integrated approach toward the understanding of peptide conformational
      dynamics. It was applied to monitor the light-induced relaxation dynamics
      occurring on subnanosecond time scales in a peptide that was backbone-cyclized
      with an azobenzene derivative as optical switch and spectroscopic probe. The
      femtosecond spectra permit the clear distinguishing and characterization of the
      subpicosecond photoisomerization of the chromophore, the subsequent dissipation
      of vibrational energy, and the subnanosecond conformational relaxation of the
      peptide. The photochemical cis/trans-isomerization of the chromophore and the
      resulting peptide relaxations have been simulated with molecular dynamics
      calculations. The calculated reaction kinetics, as monitored by the energy
      content of the peptide, were found to match the spectroscopic data. Thus we
      verify that all-atom molecular dynamics simulations can quantitatively describe
      the subnanosecond conformational dynamics of peptides, strengthening confidence
      in corresponding predictions for longer time scales.

PMID- 12060745
TI  - Obligatory heterotetramerization of three previously uncharacterized Kv channel
      alpha-subunits identified in the human genome.
AB  - Voltage-gated K(+) channels control excitability in neuronal and various other
      tissues. We identified three unique alpha-subunits of voltage-gated K(+)-channels
      in the human genome. Analysis of the full-length sequences indicated that one
      represents a previously uncharacterized member of the Kv6 subfamily, Kv6.3,
      whereas the others are the first members of two unique subfamilies, Kv10.1 and
      Kv11.1. Although they have all of the hallmarks of voltage-gated K(+) channel
      subunits, they did not produce K(+) currents when expressed in mammalian cells.
      Confocal microscopy showed that Kv6.3, Kv10.1, and Kv11.1 alone did not reach the
      plasma membrane, but were retained in the endoplasmic reticulum. Yeast two-hybrid
      experiments failed to show homotetrameric interactions, but showed interactions
      with Kv2.1, Kv3.1, and Kv5.1. Co-expression of each of the previously
      uncharacterized subunits with Kv2.1 resulted in plasma membrane localization with
      currents that differed from typical Kv2.1 currents. This heteromerization was
      confirmed by co-immunoprecipitation. The Kv2 subfamily consists of only two
      members and uses interaction with "silent subunits" to diversify its function.
      Including the subunits described here, the "silent subunits" represent one-third
      of all Kv subunits, suggesting that obligatory heterotetramer formation is more
      widespread than previously thought.

PMID- 12060747
TI  - Reduced-dimensionality NMR spectroscopy for high-throughput protein resonance
      assignment.
AB  - A suite of reduced-dimensionality (13)C,(15)N,(1)H-triple-resonance NMR
      experiments is presented for rapid and complete protein resonance assignment.
      Even when using short measurement times, these experiments allow one to retain
      the high spectral resolution required for efficient automated analysis. "Sampling
      limited" and "sensitivity limited" data collection regimes are defined,
      respectively, depending on whether the sampling of the indirect dimensions or the
      sensitivity of a multidimensional NMR experiments per se determines the minimally
      required measurement time. We show that reduced-dimensionality NMR spectroscopy
      is a powerful approach to avoid the "sampling limited regime"--i.e., a standard
      set of ten experiments proposed here allows one to effectively adapt minimal
      measurement times to sensitivity requirements. This is of particular interest in
      view of the greatly increased sensitivity of NMR spectrometers equipped with
      cryogenic probes. As a step toward fully automated analysis, the program
      AUTOASSIGN has been extended to provide sequential backbone and (13)C(beta)
      resonance assignments from these reduced-dimensionality NMR data.

PMID- 12060748
TI  - Simulations of beta-hairpin folding confined to spherical pores using distributed
      computing.
AB  - We report the thermodynamics and kinetics of an off-lattice Go model beta-hairpin
      from Ig-binding protein confined to an inert spherical pore. Confinement enhances
      the stability of the hairpin due to the decrease in the entropy of the unfolded
      state. Compared with their values in the bulk, the rates of hairpin formation
      increase in the spherical pore. Surprisingly, the dependence of the rates on the
      pore radius, R(s), is nonmonotonic. The rates reach a maximum at R(s)/R(g,N)(b)
      approximately equal to 1.5, where R(g,N)(b) is the radius of gyration of the
      folded beta-hairpin in the bulk. The denatured state ensemble of the encapsulated
      beta-hairpin is highly structured even at substantially elevated temperatures.
      Remarkably, a profound effect of confinement is evident even when the beta
      hairpin occupies less than a 10th of the sphere volume. Our calculations show
      that the emergence of substantial structure in the denatured state of proteins in
      inert pores is a consequence of confinement. In contrast, the structure of the
      bulk denatured state ensemble depends dramatically on the extent of denaturation.

PMID- 12060750
TI  - Mutational switch of an IL-6 response to an interferon-gamma-like response.
AB  - Signaling through Janus kinases (JAKs) and signal transducers and activators of
      transcription (STATs) is central to the responses to the majority of cytokines
      and some growth factors, including the interferons (IFNs) and the IL-6 family of
      cytokines. The biological responses to stimulation through the widely distributed
      IL-6 and IFN-gamma receptors are, however, completely different. Remarkably, it
      is shown here that, in mouse embryo fibroblasts lacking STAT3, IL-6 mediates an
      IFN-gamma-like response including prolonged activation of STAT1, the induction of
      multiple IFN-gamma-inducible genes, the expression of class II MHC antigens, and
      an antiviral state. Normal cells exposed to IL-6 thus require a STAT3-dependent
      function(s) to down-regulate STAT1 activity and prevent an IFN-gamma-like
      response. The data encourage the view that the very disparate IFN-gamma and IL-6
      JAK/receptor complexes mediate a common set of generic or "core" signals which
      are subject to STAT3-dependent modulation to provide IL-6 specificity. The
      switching of one cytokine response to one closely mimicking another as a result
      of the loss of a single signaling component has profound implications, for
      example, for the interpretation of the phenotypes of knockout mice and for the
      clinical use of inhibitors of signaling.

PMID- 12060749
TI  - Cell surface expression of the HIV-1 envelope glycoproteins is directed from
      intracellular CTLA-4-containing regulated secretory granules.
AB  - The envelope glycoprotein (Env) of HIV-1 is incorporated into virions that bud
      from the cell surface of infected T cells. With immunofluorescence microscopy and
      subcellular membrane fractionation techniques, the intracellular fate of Env in
      the secretory pathway of HIV-1-infected T cells was evaluated. Rather than
      trafficking constitutively from the Golgi to the cell surface, Env is directed to
      intracellular CTLA-4-containing granules, whose recruitment to the cell surface
      is regulated. The use of the regulated pathway for intracellular Env storage
      before virion assembly holds implications for the staging of Env exposure at the
      cell surface of infected cells and of coordinating HIV virion assembly.

PMID- 12060752
TI  - DT40 cells lacking the Ca2+-binding protein annexin 5 are resistant to Ca2+
      dependent apoptosis.
AB  - Annexins are widely expressed Ca(2+)-dependent phospholipid-binding proteins with
      poorly understood physiological roles. Proposed functions include Ca(2+) channel
      activity and vesicle trafficking, but neither have been proven in vivo. Here we
      used targeted gene disruption to generate B-lymphocytes lacking annexin 5 (Anx5)
      expression and show that this results in reduced susceptibility to a range of
      apoptotic stimuli. By comparison B-lymphocytes lacking annexin 2 (Anx2) showed no
      such resistance, providing evidence that this effect is specific to loss of Anx5.
      The defect in the ANX5(-/-) cells occurs early in the apoptotic program before
      nuclear condensation, caspase 3 activation, and cell shrinkage, but downstream of
      an initial Ca(2+) influx. Only UVA/B irradiation induced similar levels of
      apoptosis in wild-type and ANX5(-/-) cells. Unexpectedly, ANX5(-/-) cells
      permeabilized in vitro also failed to release mitochondrial cytochrome C,
      suggesting a possible mechanism for their resistance to apoptosis. These findings
      demonstrate a role for Anx5 in determining the susceptibility of B-lymphocytes to
      apoptosis.

PMID- 12060751
TI  - Integration of Runx and Smad regulatory signals at transcriptionally active
      subnuclear sites.
AB  - Runx factors control lineage commitment and are transcriptional effectors of Smad
      signaling. Genetic defects in these pathways interfere with normal development.
      The in situ localization of Runx and Smad proteins must impact the mechanisms by
      which these proteins function together in gene regulation. We show that the
      integration of Runx and Smad signals is mediated by in situ interactions at
      specific foci within the nucleus. Activated Smads are directed to these
      subnuclear foci only in the presence of Runx proteins. Smad-Runx complexes are
      associated in situ with the nuclear matrix, and this association requires the
      intranuclear targeting signal of Runx factors. The convergence of Smad and Runx
      proteins at these sites supports transcription as reflected by BrUTP labeling and
      functional cooperativity between the proteins. Thus, Runx-mediated intranuclear
      targeting of Smads is critical for the integration of two distinct pathways
      essential for fetal development.

PMID- 12060753
TI  - Autoinhibition of the ligand-binding site of GGA1/3 VHS domains by an internal
      acidic cluster-dileucine motif.
AB  - The GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-binding
      proteins) are a family of proteins implicated in protein trafficking from the
      Golgi to endosomes/lysosomes. These proteins have modular structures with an N
      terminal VHS (VPS-27, Hrs, and STAM) domain followed by a GAT (GGA and TOM1)
      domain, a connecting hinge segment, and a C-terminal GAE (gamma-adaptin ear)
      domain. Isolated VHS domains have been shown to bind specifically to acidic
      cluster (AC)-dileucine motifs present in the cytoplasmic tails of the mannose 6
      phosphate receptors. Here we report that full-length cytoplasmic GGA1 and GGA3
      but not GGA2 bind the cation-independent mannose 6-phosphate receptor very poorly
      because of autoinhibition. This inhibition is caused by the binding of an AC-LL
      sequence present in the hinge segment to the ligand-binding site in the VHS
      domain. The inhibition depends on the phosphorylation of a serine located three
      residues upstream of the AC-LL motif. The serine is phosphorylated by casein
      kinase 2 in in vitro assays. Substitution of the GGA1 inhibitory sequence into
      the analogous location in GGA2, which lacks the AC-LL motif, results in
      autoinhibition of the latter protein. These data indicate that the activity of
      GGA1 and GGA3 is regulated by cycles of phosphorylation/dephosphorylation.

PMID- 12060754
TI  - Transient expression of the bHLH factor neurogenin-2 marks a subpopulation of
      neural crest cells biased for a sensory but not a neuronal fate.
AB  - Lineage-tracing experiments have indicated that some premigratory neural crest
      cells (NCCs) are pleuripotent, generating sensory and sympathetic neurons and
      their associated glia. Using an inducible Cre recombinase-based fate mapping
      system, we have permanently marked a subpopulation of NCCs that expresses Ngn2, a
      bHLH transcription factor required for sensory neurogenesis, and compared its
      fate to the bulk NCC population marked by expression of Wnt1. Ngn2(+) progenitors
      were four times more likely than Wnt1(+) NCCs to contribute to sensory rather
      than sympathetic ganglia. Within dorsal root ganglia, however, both Ngn2- and
      Wnt1-expressing cells were equally likely to generate neurons or glia. These data
      suggest that Ngn2 marks an NCC subpopulation with a predictable fate bias, early
      in migration. Taken together with previous work, these data suggest that NCCs
      become restricted to sensory or autonomic sublineages before becoming committed
      to neuronal or glial fates.

PMID- 12060756
TI  - Bioavailability of organic matter in a highly disturbed estuary: the role of
      detrital and algal resources.
AB  - The importance of algal and detrital food supplies to the planktonic food web of
      a highly disturbed, estuarine ecosystem was evaluated in response to declining
      zooplankton and fish populations. We assessed organic matter bioavailability
      among a diversity of habitats and hydrologic inputs over 2 years in San Francisco
      Estuary's Sacramento-San Joaquin River Delta. Results show that bioavailable
      dissolved organic carbon from external riverine sources supports a large
      component of ecosystem metabolism. However, bioavailable particulate organic
      carbon derived primarily from internal phytoplankton production is the dominant
      food supply to the planktonic food web. The relative importance of phytoplankton
      as a food source is surprising because phytoplankton production is a small
      component of the ecosystem's organic-matter mass balance. Our results indicate
      that management plans aimed at modifying the supply of organic matter to
      riverine, estuarine, and coastal food webs need to incorporate the potentially
      wide nutritional range represented by different organic matter sources.

PMID- 12060757
TI  - A methodological bias toward overestimation of molecular evolutionary time
      scales.
AB  - There is presently a conflict between fossil- and molecular-based evolutionary
      time scales. Molecular approaches for dating the branches of the tree of life
      frequently lead to substantially deeper times of divergence than those inferred
      by paleontologists. The discrepancy between molecular and fossil estimates
      persists despite the booming growth of sequence data sets, which increasingly
      feeds the interpretation that molecular estimates are older than stratigraphic
      dates because of deficiencies in the fossil record. Here we show that molecular
      time estimates suffer from a methodological handicap, namely that they are
      asymmetrically bounded random variables, constrained by a nonelastic boundary at
      the lower end, but not at the higher end of the distribution. This introduces a
      bias toward an overestimation of time since divergence, which becomes greater as
      the length of the molecular sequence and the rate of evolution decrease.

PMID- 12060755
TI  - Hoxa 11 is upstream of Integrin alpha8 expression in the developing kidney.
AB  - Mutation of the functionally redundant Hoxa 11/Hoxd 11 genes gives absent or
      rudimentary kidneys resulting from a dramatic reduction of the growth and
      branching of the ureteric bud. To understand better the molecular mechanisms of
      Hoxa 11/Hoxd 11 function in kidney development, it is necessary to identify the
      downstream target genes regulated by their encoded transcription factors. To this
      end, we conducted a screen for Hoxa 11-responsive genes in two kidney cell lines.
      HEK293 cells, which usually do not express Hoxa 11, were modified to allow
      inducible Hoxa 11 expression. The mK10 cells, derived specifically for this study
      from Hoxa 11/Hoxd 11 double-mutant mice, were also modified to give cell
      populations with and without Hoxa 11 expression. Differential display, Gene
      Discovery Arrays, and Affymetrix genechip probe arrays were used to screen for
      genes up- or down-regulated by Hoxa 11. Nine genes, PDGF A, Cathepsin L, annexin
      A1, Mm.112139, Est2 repressor factor, NrCAM, ZNF192, integrin-associated protein,
      and GCM1, showed reproducible 3-fold or smaller changes in gene expression in
      response to Hoxa 11. One gene, the Integrin alpha8, was up-regulated
      approximately 20-fold after Hoxa 11 expression. The Integrin alpha8 gene is
      expressed together with Hoxa 11 in metanephric mesenchyme cells, and mutation of
      Integrin alpha8 gives a bud-branching morphogenesis defect very similar to that
      observed in Hoxa 11/Hoxd 11 mutant mice. In situ hybridizations showed a dramatic
      regional reduction in Integrin alpha8 expression in the developing kidneys of
      Hoxa 11/Hoxd 11 mutant mice. This work suggests that the Integrin alpha8 gene may
      be a major effector of Hoxa 11/Hoxd 11 function in the developing kidney.

PMID- 12060758
TI  - Intron presence-absence polymorphism in Drosophila driven by positive Darwinian
      selection.
AB  - Comparisons of intron-exon structures between homologous genes in different
      eukaryotic species have revealed substantial variation in the number of introns.
      These observations imply that, in each case, an intron presence-absence
      polymorphism must have existed in the past. Such a polymorphism, created by a
      recent intron-loss mutation, is reported here in a eukaryotic organism. This gene
      structure, detected in the jingwei (jgw) gene, segregates at high frequency (77%)
      in natural populations of Drosophila teissieri and is associated with a marked
      change in mRNA levels. Furthermore, the intron loss does not result from a mRNA
      mediated mechanism as is usually proposed, but from a partial deletion at the DNA
      level that also results in the addition of four new amino acids to the JGW
      protein. Population genetic analyses of the pattern of nucleotide variation
      surrounding the intron polymorphism indicate the action of positive Darwinian
      selection on the intron-absent variant. Forward simulations suggest that the
      intensity of this selection is weak to moderate, roughly equal to the selection
      intensity on most replacement mutations in Drosophila.

PMID- 12060759
TI  - Genes encoding plastid acetyl-CoA carboxylase and 3-phosphoglycerate kinase of
      the Triticum/Aegilops complex and the evolutionary history of polyploid wheat.
AB  - The classic wheat evolutionary history is one of adaptive radiation of the
      diploid Triticum/Aegilops species (A, S, D), genome convergence and divergence of
      the tetraploid (Triticum turgidum AABB, and Triticum timopheevii AAGG) and
      hexaploid (Triticum aestivum, AABBDD) species. We analyzed Acc-1 (plastid acetyl
      CoA carboxylase) and Pgk-1 (plastid 3-phosphoglycerate kinase) genes to determine
      phylogenetic relationships among Triticum and Aegilops species of the wheat
      lineage and to establish the timeline of wheat evolution based on gene sequence
      comparisons. Triticum urartu was confirmed as the A genome donor of tetraploid
      and hexaploid wheat. The A genome of polyploid wheat diverged from T. urartu less
      than half a million years ago (MYA), indicating a relatively recent origin of
      polyploid wheat. The D genome sequences of T. aestivum and Aegilops tauschii are
      identical, confirming that T. aestivum arose from hybridization of T. turgidum
      and Ae. tauschii only 8,000 years ago. The diploid Triticum and Aegilops
      progenitors of the A, B, D, G, and S genomes all radiated 2.5-4.5 MYA. Our data
      suggest that the Acc-1 and Pgk-1 loci have different histories in different
      lineages, indicating genome mosaicity and significant intraspecific
      differentiation. Some loci of the S genome of Aegilops speltoides and the G
      genome of T. timophevii are closely related, suggesting the same origin of some
      parts of their genomes. None of the Aegilops genomes analyzed is a close relative
      of the B genome, so the diploid progenitor of the B genome remains unknown.

PMID- 12060760
TI  - Survival without recovery after mass extinctions.
AB  - Because many survivors of mass extinctions do not participate in postrecovery
      diversifications, and therefore fall into a pattern that can be termed "Dead
      Clade Walking" (DCW), the effects of mass extinctions extend beyond the losses
      observed during the event itself. Analyses at two taxonomic levels provide a
      first-order test of the prevalence of DCWs by using simple and very conservative
      operational criteria. For four of the Big Five mass extinctions of the
      Phanerozoic, the marine genera that survived the extinction suffered
      approximately 10-20% attrition in the immediately following geologic stage that
      was significantly greater than the losses sustained in preextinction stages. The
      stages immediately following the three Paleozoic mass extinctions also account
      for 17% of all order-level losses in marine invertebrates over that interval,
      which is, again, significantly greater than that seen for the other stratigraphic
      stages (no orders are lost immediately after the end-Triassic or end-Cretaceous
      mass extinctions). DCWs are not evenly distributed among four regional molluscan
      time-series following the end-Cretaceous extinction, demonstrating the importance
      of spatial patterns in recovery dynamics. Although biotic interactions have been
      invoked to explain the differential postextinction success of clades, such
      hypotheses must be tested against alternatives that include stochastic processes
      in low-diversity lineages-which is evidently not a general explanation for the
      ordinal DCW patterns, because postextinction fates are not related to the size of
      extinction bottlenecks in Paleozoic orders-and ongoing physical environmental
      changes.

PMID- 12060761
TI  - Adaptive evolution of small heat shock protein/alpha B-crystallin promoter
      activity of the blind subterranean mole rat, Spalax ehrenbergi.
AB  - Blind mole rats have degenerated subcutaneous eyes that are visually
      nonfunctional. In this investigation, we have compared the tissue specificity of
      the small heat shock protein (shsp)/alphaB-crystallin promoter of the mole rat
      superspecies, Spalax ehrenbergi, with that of the mouse. Earlier experiments
      showed that mouse shsp/alphaB-crystallin promoter/enhancer activity is high in
      the lens and moderate in the heart and skeletal muscle of transgenic mice. Here,
      we show in transgenic mouse experiments using the firefly luciferase reporter
      gene that, despite relatively few changes in sequence, the mole rat shsp/alphaB
      crystallin promoter/enhancer has selectively lost lens activity after 13.5 days
      of embryogenesis (E13.5). The ratios of mole rat/mouse promoter activity were
      0.01 for lens, 1.7 for heart, and 13.6 for skeletal muscle in 8-wk-old transgenic
      mice. Our data indicate that the shsp/alphaB-crystallin promoter/enhancer has
      undergone adaptive changes corresponding to the subterranean evolution of the
      blind mole rat. We speculate that selective pressures on metabolic economy may
      have contributed to these tissue-specific modifications of promoter/enhancer
      function during adaptation to life underground.

PMID- 12060762
TI  - Comparative genomic analysis in the region of a major Plasmodium-refractoriness
      locus of Anopheles gambiae.
AB  - We have sequenced six overlapping clones from a library of bacterial artificial
      chromosome (BAC) clones derived from a laboratory strain of the mosquito,
      Anopheles gambiae, the major vector of human malaria in Africa. The resulting
      uninterrupted 528-kb sequence is from the 8C region of the mosquito 2R
      chromosome, at or very near the major refractoriness locus associated with
      melanotic encapsulation of parasites. This sequence represents the first
      extensive view of the mosquito genome structure encompassing 48 genes. Genomic
      comparison reveals that the majority of the orthologues are found in six
      microsyntenic clusters in Drosophila melanogaster. A BAC clone that is wholly
      contained within this region demonstrates the existence of a remarkable degree of
      local polymorphism in this species, which may prove important for its population
      structure and vectorial capacity.

PMID- 12060763
TI  - Regulation of alternative splicing by a transcriptional enhancer through RNA pol
      II elongation.
AB  - Promoters and enhancers are cis-acting elements that control gene transcription
      via complex networks of protein-DNA and protein-protein interactions. Whereas
      promoters deal with putting in place the RNA polymerase, both enhancers and
      promoters can control transcriptional initiation and elongation. We have
      previously shown that promoter structure modulates alternative splicing,
      strengthening the concept of a physical and functional coupling between
      transcription and splicing. Here we report that the promoter effect is due to the
      control of RNA pol II elongation. We found that the simian virus 40 (SV40)
      transcriptional enhancer, inserted in fibronectin (FN) minigene constructs
      transfected into mammalian cells, controls alternative splicing by inhibiting
      inclusion of the FN extra domain I (EDI) exon into mature mRNA. Deletion analysis
      of enhancer subdomains and competitions in vivo with excess of specific enhancer
      DNA subfragments demonstrate that the "minimal" enhancer, consisting of two 72-bp
      repeats, is responsible for the splicing effect. The 72-bp repeat region has been
      reported to promote RNA pol II elongation. When transcription is driven by the
      alpha-globin promoter linked to the SV40 enhancer, basal EDI inclusion and
      activation by the SR (Ser-Arg-rich) protein SF2/ASF are much lower than with
      other promoters. Deletion of only one of the two 72-bp repeats not only provokes
      higher EDI inclusion levels but allows responsiveness to SF2/ASF. These effects
      are the consequence of a decrease in RNA pol II elongation evidenced both by an
      increase in the proportions of shorter proximal over full length transcripts and
      by higher pol II densities upstream of the alternative exon detected by chromatin
      immunoprecipitation.

PMID- 12060764
TI  - Inhibition of glycolipid shedding rescues recognition of a CD1+ T cell lymphoma
      by natural killer T (NKT) cells.
AB  - Neoplastic transformation of cells is accompanied by an aberration of cell
      surface glycolipid composition. These tumor-associated, altered
      glycosphingolipids are often shed into the tumor cell microenvironment and
      mediate immunosuppressive activity. The nature and form of glycolipids shed by a
      variety of tumor cell lines and the mechanism(s) of shedding have been well
      characterized. The murine T cell lymphoma line, L5178Y-R, is known to shed a
      tumor-associated glycolipid, gangliotriaosylceramide, into the culture medium. We
      analyzed the effect of glycolipids from L5178Y-R on antigen presentation by
      murine CD1d1 molecules. CD1d1 molecules present glycolipid antigens to a
      specialized class of T cells called natural killer T (NKT) cells that mainly
      express a T cell receptor alpha chain (Valpha14Jalpha281) associated with Vbeta
      chains of limited diversity. In the current report, we found that L5178Y-R cells
      express CD1 on their cell surface yet are unable to stimulate CD1d1-specific NKT
      cells. We hypothesized that the glycolipid(s) shed by L5178Y-R inhibited antigen
      presentation by CD1d1. Pretreatment of CD1d1(+) cells with conditioned medium
      from L5178Y-R inhibited CD1-specific stimulation of canonical (Valpha14(+)) but
      not noncanonical (Valpha5(+)) NKT cells. Exogenous addition of lipids extracted
      from L5178Y-R cells as well as purified gangliotriaosylceramide mimicked this
      effect. Inhibition of glycolipid shedding in L5178Y-R cells with d-1-phenyl-2
      hexadecanoylamino-3-morpholino-1-propanol resulted in the rescue of CD1d1
      recognition by canonical (but not noncanonical) NKT cells. These results suggest
      that one means by which certain tumor cells can evade the host's innate antitumor
      immune response is by shedding glycolipids that inhibit CD1-mediated antigen
      presentation to NKT cells.

PMID- 12060765
TI  - Allogeneic beta-islet cells correct diabetes and resist immune rejection.
AB  - Allogeneic MHC-incompatible organ or cell grafts are usually promptly rejected by
      immunocompetent hosts. Here we tested allogeneic beta-islet cell graft acceptance
      by immune or naive C57BL/6 mice rendered diabetic with streptozotocin (STZ).
      Fully MHC-mismatched insulin-producing growth-regulated beta-islet cells were
      transplanted under the kidney capsule or s.c. Although previously or
      simultaneously primed mice rejected grafts, STZ-treated diabetic mice accepted
      islet cell grafts, and hyperglycemia was corrected within 2-4 weeks in absence of
      conventional immunosuppression. Allogeneic grafts that controlled hyperglycemia
      expressed MHC antigens, were not rejected for >100 days, and resisted a challenge
      by allogeneic skin grafts or multiple injections of allogeneic cells.
      Importantly, the skin grafts were rejected in a primary fashion by the grafted
      and corrected host, indicating neither tolerization nor priming. Such strictly
      extralymphatic cell grafts that are immunologically largely ignored should be
      applicable clinically.

PMID- 12060766
TI  - Molecular characterization of antibody specificities against
      myelin/oligodendrocyte glycoprotein in autoimmune demyelination.
AB  - Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin
      destructive Abs in autoimmune central nervous system demyelinating disorders.
      Little is known about the molecular and structural basis of these pathogenic Ab
      responses. Here, we have characterized anti-MOG Ab specificities in the marmoset
      model of experimental allergic encephalomyelitis, by means of a combinatorial IgG
      Fab library. We found that a diverse population of Ig genes encodes for auto-Abs
      that exclusively recognize conformation-dependent antigenic targets on MOG. These
      antigenic domains correspond to exposed epitopes in vivo, as the Fab fragments
      recognize native MOG in situ in marmoset brain tissue. The Ab fragments described
      here represent Ab specificities that are common constituents of the humoral
      immune repertoire against MOG in outbred populations, as demonstrated by their
      ability to displace native anti-MOG Abs present in sera from MOG-immune marmosets
      and patients with multiple sclerosis. Furthermore, neuropathological analysis and
      characterization of Ab epitope specificities in animals immunized with MOG or MOG
      derived peptides revealed that only conformation-dependent Abs are associated
      with demyelinating activity, suggesting that epitope recognition is an important
      factor for Ab pathogenicity. Our findings provide novel and unexpected knowledge
      on the diversity of anti-MOG Ab responses in nonhuman primates and humans, and
      will permit the dissection of pathogenic auto-Ab properties in multiple
      sclerosis.

PMID- 12060767
TI  - ADP ribosylation of human neutrophil peptide-1 regulates its biological
      properties.
AB  - In human airways, epithelial cells lining the lumen and intraluminal cells (e.g.,
      polymorphonuclear cells) participate in the innate immune response. These cells
      secrete or express on their surfaces arginine-specific ADP ribosyltransferases.
      Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich,
      leading us to hypothesize that ADP ribosylation could modify their biological
      activities. We found that an arginine-specific ADP ribosyltransferase-1 present
      on airway epithelial cells modifies Arg-14 of alpha defensin-1. ADP-ribosylated
      defensin-1 had decreased antimicrobial and cytotoxic activities but still
      stimulated T cell chemotaxis and IL-8 release from A549 cells. Further, ADP
      ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of
      unmodified defensin-1. We identified ADP-ribosylated defensin-1 in
      bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its
      existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an
      important regulatory role in the innate immune response through modification of
      alpha defensin-1 and perhaps other basic molecules, with alteration of their
      biological properties.

PMID- 12060768
TI  - FLIP switches Fas-mediated glucose signaling in human pancreatic beta cells from
      apoptosis to cell replication.
AB  - Type 2 diabetes mellitus results from an inadequate adaptation of the functional
      pancreatic beta cell mass in the face of insulin resistance. Changes in the
      concentration of glucose play an essential role in the regulation of beta cell
      turnover. In human islets, elevated glucose concentrations impair beta cell
      proliferation and induce beta cell apoptosis via up-regulation of the Fas
      receptor. Recently, it has been shown that the caspase-8 inhibitor FLIP may
      divert Fas-mediated death signals into those for cell proliferation in lymphatic
      cells. We observed expression of FLIP in human pancreatic beta cells of
      nondiabetic individuals, which was decreased in tissue sections of type 2
      diabetic patients. In vitro exposure of islets from nondiabetic organ donors to
      high glucose levels decreased FLIP expression and increased the percentage of
      apoptotic terminal deoxynucleotidyltransferase-mediated UTP end labeling (TUNEL)
      positive beta cells; FLIP was no longer detectable in such TUNEL-positive beta
      cells. Up-regulation of FLIP, by incubation with transforming growth factor beta
      or by transfection with an expression vector coding for FLIP, protected beta
      cells from glucose-induced apoptosis, restored beta cell proliferation, and
      improved beta cell function. The beneficial effects of FLIP overexpression were
      blocked by an antagonistic anti-Fas antibody, indicating their dependence on Fas
      receptor activation. The present data provide evidence for expression of FLIP in
      the human beta cell and suggest a novel approach to prevent and treat diabetes by
      switching Fas signaling from apoptosis to proliferation.

PMID- 12060769
TI  - Targeted inactivation of CTNNB1 reveals unexpected effects of beta-catenin
      mutation.
AB  - Inactivating mutations of the adenomatous polyposis coli gene (APC) or activating
      mutations of the beta-catenin gene (CTNNB1) initiate colorectal neoplasia. To
      address the biochemical and physiologic effects of mutant beta-catenin, we
      disrupted either the mutant or wild-type CTNNB1 allele in a human colorectal
      cancer cell line. Cells with only wild-type beta-catenin had decreased colony
      forming ability when plated at low density, although their growth was similar to
      that of parental cells when passaged under routine conditions.
      Immunohistochemistry and cell-fractionation studies suggested that mutant beta
      catenin activity was distinguished primarily by cellular localization and not by
      protein degradation. Surprisingly, we found mutant beta-catenin bound less well
      to E-cadherin than did wild-type beta-catenin, and the membranous localization of
      wild-type and mutant beta-catenin was accordingly distinct. These findings pose
      several challenges to current models of APC/beta-catenin function.

PMID- 12060771
TI  - PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model.
AB  - Acute promyelocytic leukemia (APL) cells invariably express aberrant fusion
      proteins involving the retinoic acid receptor alpha (RARalpha). The most common
      fusion partner is promyelocytic leukemia protein (PML), which is fused to
      RARalpha in the balanced reciprocal chromosomal translocation, t(15;17)(q22:q11).
      Expression of PML/RARalpha from the cathepsin G promoter in transgenic mice
      causes a nonfatal myeloproliferative syndrome in all mice; about 15% go on to
      develop APL after a long latent period, suggesting that additional mutations are
      required for the development of APL. A candidate target gene for a second
      mutation is FLT3, because it is mutated in approximately 40% of human APL cases.
      Activating mutations in FLT3, including internal tandem duplication (ITD) in the
      juxtamembrane domain, transform hematopoietic cell lines to factor independent
      growth. FLT3-ITDs also induce a myeloproliferative disease in a murine bone
      marrow transplant model, but are not sufficient to cause AML. Here, we test the
      hypothesis that PML/RARalpha can cooperate with FLT3-ITD to induce an APL-like
      disease in the mouse. Retroviral transduction of FLT3-ITD into bone marrow cells
      obtained from PML/RARalpha transgenic mice results in a short latency APL-like
      disease with complete penetrance. This disease resembles the APL-like disease
      that occurs with long latency in the PML/RARalpha transgenics, suggesting that
      activating mutations in FLT3 can functionally substitute for the additional
      mutations that occur during mouse APL progression. The leukemia is transplantable
      to secondary recipients and is ATRA responsive. These observations document
      cooperation between PML/RARalpha and FLT3-ITD in development of the murine APL
      phenotype.

PMID- 12060772
TI  - A critical concentration of neutrophils is required for effective bacterial
      killing in suspension.
AB  - We have examined the effect of neutrophil concentration on killing of a clinical
      isolate of Staphylococcus epidermidis. Human neutrophils at concentrations
      varying from 10(5) to 10(7) per ml were mixed in suspension with S. epidermidis
      at concentrations varying from 10(3) to 10(8) colony-forming units/ml, and the
      concentration of viable bacteria was assayed after various times at 37 degrees C.
      The rate of bacterial killing depended on the concentration of neutrophils and
      not on the ratio of neutrophils to bacteria. Below a critical concentration of
      neutrophils, bacteria growth was greater than neutrophil killing of bacteria even
      when the ratio of neutrophils to bacteria was 100:1. We fitted the time course of
      bacterial concentration and its dependence on neutrophil concentration with an
      exponential function, the exponent of which is (-kp + g)t, where k is the second
      order rate constant for bacterial killing, p is the neutrophil concentration, g
      is the first-order rate constant for bacterial growth, and t is time. We found
      that k approximately 2 x 10(-8) ml per neutrophil per min, and g approximately 8
      x 10(-3)/min. Only when p is greater than g/k, which we call the critical
      neutrophil concentration, does the bacterial concentration fall. Under optimal
      assay conditions, the critical neutrophil concentration was 3-4 x 10(5) per ml, a
      value very close to that (< or =5 x 10(5) per ml) known to predispose humans to
      bacterial and fungal infections.

PMID- 12060770
TI  - Diversity and complexity of HIV-1 drug resistance: a bioinformatics approach to
      predicting phenotype from genotype.
AB  - Drug resistance testing has been shown to be beneficial for clinical management
      of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug
      resistance, the commonly used genotypic assays provide only indirect evidence of
      drug resistance, the major challenge being the interpretation of the sequence
      information. We analyzed the significance of sequence variations in the protease
      and reverse transcriptase genes for drug resistance and derived models that
      predict phenotypic resistance from genotypes. For 14 antiretroviral drugs, both
      genotypic and phenotypic resistance data from 471 clinical isolates were analyzed
      with a machine learning approach. Information profiles were obtained that
      quantify the statistical significance of each sequence position for drug
      resistance. For the different drugs, patterns of varying complexity were
      observed, including between one and nine sequence positions with substantial
      information content. Based on these information profiles, decision tree
      classifiers were generated to identify genotypic patterns characteristic of
      resistance or susceptibility to the different drugs. We obtained concise and
      easily interpretable models to predict drug resistance from sequence information.
      The prediction quality of the models was assessed in leave-one-out experiments in
      terms of the prediction error. We found prediction errors of 9.6-15.5% for all
      drugs except for zalcitabine, didanosine, and stavudine, with prediction errors
      between 25.4% and 32.0%. A prediction service is freely available at
      http://cartan.gmd.de/geno2pheno.html.

PMID- 12060773
TI  - Transduction of human NOD/SCID-repopulating cells with both lymphoid and myeloid
      potential by foamy virus vectors.
AB  - The efficiency of gene transfer into human hematopoietic stem cells by
      oncoretroviral vectors is too low for effective gene therapy of most hematologic
      diseases. Retroviral vectors based on the nonpathogenic foamy viruses (FV) are an
      alternative gene-transfer system. In this study, human umbilical cord blood
      CD34(+) cells were transduced with FV vectors by a single 10-h exposure to vector
      stocks and then injected into sublethally irradiated nonobese diabetic-severe
      combined immunodeficiency (NOD/SCID) mice. At 5-7 weeks after transplantation,
      high transgene expression rates were observed in engrafted human hematopoietic
      cells, including over 60% of clonogenic progenitors. Significant transgene
      silencing did not occur. We developed an approach for expanding human cell
      populations derived from transplanted mice to show that multiple SCID
      repopulating cells (SRCs) had been transduced, including some that were capable
      of both lymphoid and myeloid differentiation. These findings demonstrate for the
      first time that human pluripotent (lympho-myeloid) hematopoietic stem cells
      repopulate NOD/SCID mice and can be efficiently transduced by FV vectors.

PMID- 12060774
TI  - Of the three tegument proteins that package mRNA in herpes simplex virions, one
      (VP22) transports the mRNA to uninfected cells for expression prior to viral
      infection.
AB  - An earlier report has shown that herpes simplex virus 1 virions package RNA.
      Experiments designed to reveal the identity of the virion proteins capable of
      binding the RNA and to show whether the mRNA carried in the newly infected cells
      was expressed showed the following: (i) (32)P-labeled riboprobe generated by in
      vitro transcription of the U(S)8.5 ORF bound three proteins identified as the
      products of U(S)11, U(L)47, and U(L)49 (VP22) genes. (ii) Viral RNA was bound to
      U(L)47 or U(S)11 proteins immune precipitated from cells transduced with
      baculoviruses expressing U(L)47 or U(S)11 and then superinfected with HSV-1 under
      conditions that blocked DNA synthesis and assembly of virions. (iii) Virions were
      purified from cells transduced with a baculovirus encoding a U(S)8.5 protein
      fused to green fluorescent protein and superinfected with an HSV-1 mutant lacking
      the U(S)8-12 genes. HEp-2 cells infected with these virions expressed the
      chimeric protein in approximately 1% of infected cells. (iv) In mixed cultures,
      untreated Vero cells acquired the mRNA encoding the green fluorescent-U(S)8.5
      chimeric protein from HEp-2 cells doubly transduced with the genes encoding VP22
      and the chimeric protein. The transfer was RNase sensitive and VP22 dependent,
      indicating that the RNA encoded by the chimeric gene was transferred to Vero
      cells as mRNA. We conclude that (i) three virion proteins are capable of binding
      RNA; (ii) the packaged RNA can be expressed in newly infected cells; and (iii)
      the U(L)47 protein was earlier reported to shuttle from nucleus to the cytoplasm
      and may transport RNA. VP22 thus appears to be a member of a new class of viral
      proteins whose major function is to bind and transport infected cell mRNA to
      uninfected cells to create the environment for effective initiation of infection.

PMID- 12060775
TI  - Novel kingdom-level eukaryotic diversity in anoxic environments.
AB  - Molecular evolutionary studies of eukaryotes have relied on a sparse collection
      of gene sequences that do not represent the full range of eukaryotic diversity in
      nature. Anaerobic microbes, particularly, have had little representation in
      phylogenetic studies. Such organisms are the least known of eukaryotes and
      probably are the most phylogenetically diverse. To provide fresh perspective on
      the natural diversity of eukaryotes in anoxic environments and also to discover
      novel sequences for evolutionary studies, we conducted a cultivation-independent,
      molecular phylogenetic survey of three anoxic sediments, including both
      freshwater and marine samples. Many previously unrecognized eukaryotes were
      identified, including representatives of seven lineages that are not specifically
      related to any known organisms at the kingdom-level and branch below the
      eukaryotic "crown" radiation of animals, plants, fungi, stramenopiles, etc. The
      survey additionally identified new sequences characteristic of known ecologically
      important eukaryotic groups with anaerobic members. Phylogenetic analyses with
      the new sequences enhance our understanding of the diversity and pattern of
      eukaryotic evolution.

PMID- 12060776
TI  - Reduced immunopathology and mortality despite tissue persistence in a
      Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH.
AB  - The pathogenesis of tuberculosis involves multiple phases and is believed to
      involve both a carefully deployed series of adaptive bacterial virulence factors
      and inappropriate host immune responses that lead to tissue damage. A defined
      Mycobacterium tuberculosis mutant strain lacking the sigH-encoded transcription
      factor showed a distinctive infection phenotype. In resistant C57BL/6 mice, the
      mutant achieved high bacterial counts in lung and spleen that persisted in
      tissues in a pattern identical to those of wild-type bacteria. Despite a high
      bacterial burden, the mutant produced a blunted, delayed pulmonary inflammatory
      response, and recruited fewer CD4(+) and CD8(+) T cells to the lung in the early
      stages of infection. In susceptible C3H mice, the mutant again showed diminished
      immunopathology and was nonlethal at over 170 days after intravenous infection,
      in contrast to isogenic wild-type bacilli, which killed with a median time to
      death of 52 days. Complete genomic microarray analysis revealed that M.
      tuberculosis sigH may mediate the transcription of at least 31 genes directly and
      that it modulates the expression of about 150 others; the SigH regulon governs
      thioredoxin recycling and may be involved in the maintenance of intrabacterial
      reducing capacity. These data show that the M. tuberculosis sigH gene is
      dispensable for bacterial growth and survival within the host, but is required
      for the production of immunopathology and lethality. This phenotype demonstrates
      that beyond an ability to grow and persist within the host, M. tuberculosis has
      distinct virulence mechanisms that elicit deleterious host responses and
      progressive pulmonary disease.

PMID- 12060777
TI  - Direct biochemical evidence for type III secretion-dependent translocation of the
      AvrBs2 effector protein into plant cells.
AB  - The calmodulin-dependent adenylate cyclase domain (Cya) of the Bordetella
      pertussis cyclolysin was used as a reporter protein to study the direct
      translocation of the Xanthomonas effector protein, AvrBs2, into the plant host
      cell. Adenylate cyclase activity (production of cAMP) depends on the presence of
      eukaryotic plant calmodulin and is only active after translocation from the
      prokaryotic cell into the eukaryotic plant cell. Here, we show that infection of
      pepper plants by Xanthomonas campestris pv. vesicatoria strains expressing the
      AvrBs2:Cya fusion protein results in detectable increases of cAMP levels in plant
      cells as early as 3 h after inoculation. Adenylate cyclase activity was shown to
      be type III secretion-dependent as the Xanthomonas hrp mutations, hrcV or hrpF,
      failed to produce detectable levels of cAMP in infected pepper plants.
      Furthermore, the N-terminal secretion and translocation signals of AvrBs2 were
      shown to be required for activity of the fusion protein in the plant. A single
      genomic copy of the avrBs2:cya fusion gene expressed under the control of the
      wild-type avrBs2 promoter was used to compare the effect of a susceptible and
      resistant plant interaction on the kinetics of effector protein delivery.
      Implications of these results and additional applications of this reporter
      construct are discussed.

PMID- 12060778
TI  - An expanded view of bacterial DNA replication.
AB  - A protein-interaction network centered on the replication machinery of Bacillus
      subtilis was generated by genome-wide two-hybrid screens and systematic
      specificity assays. The network consists of 91 specific interactions linking 69
      proteins. Over one fourth of the interactions take place between homologues of
      proteins known to interact in other organisms, indicating the high biological
      significance of the other interactions we report. These interactions provide
      insights on the relations of DNA replication with recombination and repair,
      membrane-bound protein complexes, and signaling pathways. They also lead to the
      biological role of unknown proteins, as illustrated for the highly conserved
      YabA, which is shown here to act in initiation control. Thus, our interaction map
      provides a valuable tool for the discovery of aspects of bacterial DNA
      replication.

PMID- 12060779
TI  - Rapid genetic analysis of Helicobacter pylori gastric mucosal colonization in
      suckling mice.
AB  - Previously described animal models for Helicobacter pylori infection have been
      limited by cumbersome host requirements (e.g., germ-free conditions or unusual
      species) or are applicable to only special subsets of H. pylori strains (e.g.,
      fresh clinical isolates or animal-adapted derivatives). Here, we report that 5-
      to 6-day-old outbred CD-1 (ICR) suckling mice support 24-h colonization of all H.
      pylori strains tested (SS1, 26695 SmR-1, 43504 SmR-1, and G27 SmR-1), including
      lab-passaged strains that cannot be adapted for colonization of adult animals.
      Total colony-forming units (cfu) recovered from infection with lab-passaged
      strains did not differ from those with mouse-adapted SS1. We also tested this
      model's ability to detect colonization defects in strains carrying mutations in
      known virulence genes by coinfecting with wild-type H. pylori and measuring
      differential recovery. This competition assay identified colonization defects in
      several classes of known attenuated mutants, including those defective in acid
      resistance (ureA), metabolism (frdA), motility (motB), and chemotaxis (cheY). A
      mutant defective in copA (copper transporting P-type ATPase) is nonattenuated in
      adult and infant mice. Possibly because of the limited duration of infection, our
      model did not identify defects in vacuolating cytotoxin (vacA) or gamma
      glutamyltranspeptidase (ggt) as attenuating, in contrast to results from other
      animal models. We also identified a new virulence gene (HP0507) encoding a
      conserved hypothetical protein, which is important for colonization in our model.
      The suckling mouse model offers a rapid method to identify colonization defects
      in any H. pylori strain and may have utility as a new tool for studying immunity
      to primary infection.

PMID- 12060781
TI  - Endogenous cannabinoids mediate long-term synaptic depression in the nucleus
      accumbens.
AB  - Do endocannabinoids (eCBs) participate in long-term synaptic plasticity in the
      brain? Using pharmacological approaches and genetically altered mice, we show
      that stimulation of prelimbic cortex afferents at naturally occurring frequencies
      causes a long-term depression of nucleus accumbens glutamatergic synapses
      mediated by eCB release and presynaptic CB1 receptors. Translation of glutamate
      synaptic transmission into eCB retrograde signaling involved metabotropic
      glutamate receptors and postsynaptic intracellular Ca(2+) stores. These findings
      unveil the role of the eCB system in activity-dependent long-term synaptic
      plasticity and identify a mechanism by which marijuana can alter synaptic
      functions in the endogenous brain reward system.

PMID- 12060782
TI  - A missense mutation in human fatty acid amide hydrolase associated with problem
      drug use.
AB  - Problem drug use and dependence are neurobehavioral disorders of complex origin.
      Although environmental factors contribute to drug abuse and addiction, genetic
      factors also play a significant role estimated at 40-60% of the total risk.
      Nonetheless, the precise identities of human genes that confer vulnerability to
      problem drug use remain mostly unknown. Here, we describe a natural single
      nucleotide polymorphism in the human gene that encodes the principal
      endocannabinoid-inactivating enzyme, fatty acid amide hydrolase (FAAH), that in
      homozygous form is strongly associated with both street drug use and problem
      drug/alcohol use. This single nucleotide polymorphism results in a missense
      mutation (385C-->A) that converts a conserved proline residue to threonine
      (Pro129-->Thr), producing a FAAH variant that displays normal catalytic
      properties but an enhanced sensitivity to proteolytic degradation. Collectively,
      these results suggest that genetic mutations in FAAH may constitute important
      risk factors for problem drug use and support a potential link between functional
      abnormalities in the endogenous cannabinoid system and drug abuse and dependence.

PMID- 12060783
TI  - An endogenous capsaicin-like substance with high potency at recombinant and
      native vanilloid VR1 receptors.
AB  - The vanilloid receptor VR1 is a nonselective cation channel that is most abundant
      in peripheral sensory fibers but also is found in several brain nuclei. VR1 is
      gated by protons, heat, and the pungent ingredient of "hot" chili peppers,
      capsaicin. To date, no endogenous compound with potency at this receptor
      comparable to that of capsaicin has been identified. Here we examined the
      hypothesis, based on previous structure-activity relationship studies and the
      availability of biosynthetic precursors, that N-arachidonoyl-dopamine (NADA) is
      an endogenous "capsaicin-like" substance in mammalian nervous tissues. We found
      that NADA occurs in nervous tissues, with the highest concentrations being found
      in the striatum, hippocampus, and cerebellum and the lowest concentrations in the
      dorsal root ganglion. We also gained evidence for the existence of two possible
      routes for NADA biosynthesis and mechanisms for its inactivation in rat brain.
      NADA activates both human and rat VR1 overexpressed in human embryonic kidney
      (HEK)293 cells, with potency (EC(50) approximately 50 nM) and efficacy similar to
      those of capsaicin. Furthermore, NADA potently activates native vanilloid
      receptors in neurons from rat dorsal root ganglion and hippocampus, thereby
      inducing the release of substance P and calcitonin gene-related peptide (CGRP)
      from dorsal spinal cord slices and enhancing hippocampal paired-pulse depression,
      respectively. Intradermal NADA also induces VR1-mediated thermal hyperalgesia
      (EC(50) = 1.5 +/- 0.3 microg). Our data demonstrate the existence of a brain
      substance similar to capsaicin not only with respect to its chemical structure
      but also to its potency at VR1 receptors.

PMID- 12060786
TI  - Paranasal sinus anatomy of Aegyptopithecus: implications for hominoid origins.
AB  - The East African Early Miocene apes, or proconsulids, have often been considered
      to be among the earliest members of the Hominoidea, as defined by the divergence
      of the Cercopithecoidea, but this hypothesis is only weakly supported by
      available fossil evidence. The ethmofrontal sinus is one of a few morphological
      features that may link proconsulids with later hominoids. Here we present direct
      evidence of an ethmofrontal sinus in an early Oligocene stem catarrhine,
      Aegyptopithecus zeuxis. The presence of this sinus in Aegyptopithecus suggests
      that its presence in proconsulids is most likely to be a retained primitive
      condition. The morphological evidence bearing on proconsulids' purported hominoid
      affinities is further weakened by this conclusion, and alternative phylogenetic
      possibilities, such as the placement of proconsulids as stem catarrhines are
      considered more likely.

PMID- 12060785
TI  - Life-long sustained mortality advantage of siblings of centenarians.
AB  - Although survival to old age is known to have strong environmental and behavioral
      components, mortality differences between social groups tend to diminish or even
      disappear at older ages. Hypothesizing that surviving to extreme old age entails
      a substantial familial predisposition for longevity, we analyzed the pedigrees of
      444 centenarian families in the United States. These pedigrees included 2,092
      siblings of centenarians, whose survival was compared with 1900 birth cohort
      survival data from the U.S. Social Security Administration. Siblings of
      centenarians experienced a mortality advantage throughout their lives relative to
      the U.S. 1900 cohort. Female siblings had death rates at all ages about one-half
      the national level; male siblings had a similar advantage at most ages, although
      diminished somewhat during adolescence and young adulthood. Relative survival
      probabilities for these siblings increase markedly at older ages, reflecting the
      cumulative effect of their mortality advantage throughout life. Compared with the
      U.S. 1900 cohort, male siblings of centenarians were at least 17 times as likely
      to attain age 100 themselves, while female siblings were at least 8 times as
      likely.

PMID- 12060784
TI  - Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein
      (MAG), an inhibitor of nerve regeneration.
AB  - Myelin-associated glycoprotein (MAG) binds to the nerve cell surface and inhibits
      nerve regeneration. The nerve cell surface ligand(s) for MAG are not established,
      although sialic acid-bearing glycans have been implicated. We identify the nerve
      cell surface gangliosides GD1a and GT1b as specific functional ligands for MAG
      mediated inhibition of neurite outgrowth from primary rat cerebellar granule
      neurons. MAG-mediated neurite outgrowth inhibition is attenuated by (i)
      neuraminidase treatment of the neurons; (ii) blocking neuronal ganglioside
      biosynthesis; (iii) genetically modifying the terminal structures of nerve cell
      surface gangliosides; and (iv) adding highly specific IgG-class antiganglioside
      mAbs. Furthermore, neurite outgrowth inhibition is mimicked by highly multivalent
      clustering of GD1a or GT1b by using precomplexed antiganglioside Abs. These data
      implicate the nerve cell surface gangliosides GD1a and GT1b as functional MAG
      ligands and suggest that the first step in MAG inhibition is multivalent
      ganglioside clustering.

PMID- 12060780
TI  - Identification of gene expression profile of dorsal root ganglion in the rat
      peripheral axotomy model of neuropathic pain.
AB  - Phenotypic modification of dorsal root ganglion (DRG) neurons represents an
      important mechanism underlying neuropathic pain. However, the nerve injury
      induced molecular changes are not fully identified. To determine the molecular
      alterations in a broader way, we have carried out cDNA array on the genes mainly
      made from the cDNA libraries of lumbar DRGs of normal rats and of rats 14 days
      after peripheral axotomy. Of the 7,523 examined genes and expressed sequence tags
      (ESTs), the expression of 122 genes and 51 expressed sequence tags is strongly
      changed. These genes encompass a large number of members of distinct families,
      including neuropeptides, receptors, ion channels, signal transduction molecules,
      synaptic vesicle proteins, and others. Of particular interest is the up
      regulation of gamma-aminobutyric acid(A) receptor alpha5 subunit, peripheral
      benzodiazepine receptor, nicotinic acetylcholine receptor alpha7 subunit, P2Y1
      purinoceptor, Na(+) channel beta2 subunit, and L-type Ca(2+) channel alpha2delta
      1 subunit. Our findings therefore reveal dynamic and complex changes in molecular
      diversity among DRG neurons after axotomy. Sequences reported in this paper have
      been deposited in the GenBank database (accession numbers BG 662484-BG 673712)

PMID- 12060787
TI  - KSR--a regulator and scaffold protein of the MAPK pathway.
AB  - Raabe and Rapp discuss how the scaffolding proteins may spatially localize
      mitogen-activated protein kinase (MAPK) signaling cassettes to allow signaling
      specificity. They focus on the adaptor kinase suppressor of Ras (KSR) and
      describe how the interactions between KSR and other proteins and the subcellular
      localization of KSR are regulated by phosphorylation.

PMID- 12060788
TI  - The slice overlay assay: a versatile tool to study the influence of extracellular
      signals on neuronal development.
AB  - We have developed a technique that allows characterization and identification of
      extracellular signals that regulate various aspects of neuronal differentiation.
      In this in vitro assay, dissociated cells isolated from the developing cerebral
      wall are labeled and cultured over organotypic cortical slices. We have used this
      slice overlay assay to identify some of the extracellular cues that regulate
      differentiation and patterning of axons and dendrites in the cerebral cortex.
      This assay can be easily adapted to identify factors that control other aspects
      of neuronal development, such as proliferation and survival, and can also be used
      to evaluate the role of extracellular signals in the development of nonneural
      tissues.

PMID- 12060789
TI  - Seeing is believing? The form and substance of French medical debates over
      Lourdes.
AB  - Recent works on Lourdes have tended to emphasize the positive personal, social,
      and spiritual aspects of a pilgrimage, while downplaying the role of religious
      politics in (over)determining discussions around the events taking place there
      over the course of the Third Republic. This paper seeks to reassert the extent to
      which the medical community remained divided, along religious lines, over the
      existence and nature of the cures taking place at Lourdes well into the twentieth
      century, while analyzing how Catholic physicians were able to create an aura of
      therapeutic credibility around the cures.

PMID- 12060790
TI  - Making the unit of insulin: standards, clinical work, and industry, 1920-1925.
AB  - The standardization of insulin is generally considered by historians to have been
      a process conducted by physiologists under the direction of Henry Dale. This
      article shows that it actually involved many actors and began with the earliest
      administration to patients in Canada and the United States. During this first
      phase, the drug company Eli Lilly also contributed actively to the
      standardization, under the scientific direction of George Clowes. This is not to
      undermine the role of Dale, whose political leadership was paramount for the
      international phase of the standardization. His scientific contribution, however,
      was a continuation of previous work led by physiologists, clinicians, and
      pharmacists. The production and packaging of insulin in standardized units thus
      appears to be the result of the impressive working of a transdisciplinary and
      transnational network. It also highlights how new modes of drug regulation were
      elaborated by state bodies in the early 1920s and paved the way for more
      extensive reforms.

PMID- 12060791
TI  - Rooming-in: redesigning hospitals and motherhood in cold war America.
AB  - Rooming-in, a model of maternity care that placed newborns in their mothers'
      rooms instead of central nurseries, appeared in American hospitals in the early
      1940s, advocated by physicians and mothers as an antidote to the emotional
      sterility of the modern maternity ward. It has been cited as a successful
      illustration of health-care reform, in which practitioners and patients
      redesigned postpartum care to make it more fulfilling. However, factors other
      than visionary leadership contributed to the establishment and popularity of
      rooming-in. First, wartime changes in the medical care of postpartum patients,
      including antibiotic therapy and early ambulation, paved the way for a system in
      which mothers played an active role. Second, rooming-in effectively solved two
      hospital crises: a nursing shortage, and an epidemic of infections in newborn
      nurseries. Finally, it achieved notoriety far beyond its actual prevalence
      because it resonated with trends in mass culture: a wariness of technology,
      interest in the causes and prevention of neurosis, and the "feminine mystique."
      This article suggests that changes in health care depend less on reasoned
      planning than on coincidental events inside and outside the hospital.

PMID- 12060792
TI  - From screening to clinical research: the cure of leukemia and the early
      development of the cooperative oncology groups, 1955-1966.
AB  - Recent work in the history and sociology of biomedicine has emphasized the
      novelty of the biomedical enterprise as a distinctive institutional, material,
      and epistemological configuration. Since World War II, biology and medicine have
      become such tightly intertwined research enterprises that those working in
      biomedicine cannot predict whether a particular research project, clinical
      investigation, or even clinical intervention will result in biological or medical
      facts. In this paper, we examine part of the process of the emergence of
      biomedicine by focusing on the development of clinical cancer trials in the
      United States in the years 1955-66, a period during which the clinical trials
      program run by the National Cancer Institute became autonomous from the
      Institute's screening program for anticancer compounds. We examine in particular
      the work carried out by the cooperative groups and the Acute Leukemia Task Force
      to which they belonged, analyzing the evolution of the relations between
      screening, chemotherapy, clinical trials, and clinical research.

PMID- 12060793
TI  - The collected papers of Paul Ehrlich : why was volume 4 never published?
AB  - In the 1950s, Sir Henry Hallett Dale undertook to compile and publish all the
      scientific papers of Nobel laureate Paul Ehrlich. He was assisted in this venture
      by Dr. Fred Himmelweit and by Ehrlich's former secretary, Martha Marquardt. A
      four-volume series was announced, but only three volumes saw the light of day,
      between 1957 and 1960. This report presents the result of a five-year effort to
      determine the reason for the failure to complete the undertaking, in which all
      potential sources were pursued and queried. In the end, the mystery remains
      unsolved.

PMID- 12060794
TI  - Roles of orexins in regulation of feeding and wakefulness.
AB  - Maintenance of energy homeostasis requires the coordination of systems that
      regulate feeding, body temperature, autonomic and endocrine functions with those
      that govern an appropriate state of arousal (wakefulness). Historically, the
      hypothalamus has been recognized to play a critical role in maintaining energy
      homeostasis by integrating these factors and coordinating metabolic,
      neuroendocrine and behavioral responses and arousal states. Recent studies have
      suggested that orexin-containing neurons in the lateral hypothalamic area (LHA)
      constitute an important central pathway that promotes adaptive behavioral and
      arousal responses to metabolic and environmental signals. Orexins, also called
      hypocretins, are neuropeptides originally identified as endogenous ligands for
      two orphan G-protein-coupled receptors termed orexin receptors -1 and -2. Orexin
      A and -B are expressed by a specific population of neurons in the LHA. These
      neurons project to numerous brain regions, with monoaminergic and cholinergic
      nuclei of the hypothalamus, midbrain, and pons receiving particularly strong
      innervations. The orexinergic system is anatomically well-placed to coordinate
      the metabolic, motivational, motor, autonomic, and arousal processes necessary to
      elicit environmentally appropriate behaviors. Recent studies on orexin suggest
      that the orexinergic system plays a significant role in feeding and sleep
      wakefulness regulation, possibly by coordinating the complex behavioral and
      physiological responses of these complementary homeostatic functions. Orexin
      neurons may provide an integrative link between peripheral metabolism and central
      regulation of behaviors required for an adaptive response to homeostatic
      challenges.

PMID- 12060795
TI  - Specific forms of neural activity associated with tactile space awareness.
AB  - Left tactile extinction, in which a left tactile stimulus fails to access
      consciousness only when a right stimulus is presented simultaneously, offers a
      model for studying tactile awareness from its transitory absence. Pairs of
      transcranial magnetic stimuli (TMS) on the parietal cortex inhibit contralateral
      tactile perception when separated by an interval of 1 ms. We have applied this
      technique on the left parietal cortex of right brain damaged (RBD) patients and
      normal subjects and have shown a selective lack of paired TMS inhibitory effects
      on right tactile perception of patients during bimanual stimulation. TMS effects
      were normal during unimanual right stimulation. These results suggest the
      presence of a specific pattern of inhibitory/excitatory interactions in parietal
      brain areas as critical for tactile awareness.

PMID- 12060796
TI  - Therapeutic time window for YAG laser-induced reperfusion of thrombotic stroke in
      hypertensive rats.
AB  - We examined the novel YAG laser-induced reperfusion method in the photothrombotic
      middle cerebral artery (MCA) occlusion model in spontaneously hypertensive rats.
      In the 1 h ischemia group, infarct volume was significantly reduced to 41.1 +/-
      15.6 mm3 compared with 81.6 +/- 18.3 mm3 in the no-reperfusion group. There were
      no significant differences in infarct volume among 2 h or 3 h ischemia and no
      reperfusion groups. Three of six rats in the 3 h ischemia group showed
      hemorrhagic infarction. Our present results showed that recirculation must be
      instituted within 2 h of MCA occlusion to get beneficial effects in our model,
      supporting the concept of a narrow therapeutic time window for intervention in
      ischemic stroke.

PMID- 12060797
TI  - Pre-perceptual pain sensory responses (N1 component) in type 1 diabetes mellitus.
AB  - We investigated the integrity of the ascending pathways for pain sensitivity in
      the early stage of type 1 diabetes mellitus, by measuring the N1 component and
      the conventional N2/P2 vertex potentials of laser evoked potentials (LEPs). Brain
      responses to laser stimuli were obtained in 21 healthy volunteers and 21 type 1
      diabetic patients, without either clinical neuropathy or electrophysiological
      evidence of large-fiber damage. In diabetic patients N1 and P2 latencies were
      prolonged and the N1 and N2/P2 amplitudes were decreased after foot stimulation.
      A significant reduction of the conduction velocity of Adelta fibers in the lower
      limbs was also observed. LEPs reveal an early, subclinical and selective damage
      of pain sensation in diabetic patients. N1 and P2 potentials are delayed and
      decreased in parallel giving evidence that LEP abnormalities are not secondary to
      a cognitive dysfunction and mostly reflect a small-fiber dysfunction.

PMID- 12060798
TI  - CaMKII regulates amphetamine-induced ERK1/2 phosphorylation in striatal neurons.
AB  - Amphetamine activates extracellular signal-regulated kinase 1 and 2 (ERK1/2)
      resulting in cAMP response element-binding protein (CREB) and Elk-1
      phosphorylation in striatal neurons. In the present study we investigated whether
      calcium and calmodulin-dependent protein kinase II (CaMKII) regulates amphetamine
      induced ERK1/2 pathways in striatal neurons using Western blot and
      immunohistochemical analysis. Acute administration of amphetamine (5 mg/kg, i.p.)
      increased phosphorylated (p)CaMKII immunoreactivity. Inhibition of CaMKII by
      intrastriatal infusion of KN62 (2, 10, or 25 nmol) attenuated amphetamine-induced
      increases in pERK1/2, pCREB, and pElk-1 immunoreactivity in the ipsilateral
      dorsal striatum in a dose-dependent manner. These data suggest that CaMKII
      controls amphetamine-activated ERK1/2 pathways in striatal neurons in vivo.

PMID- 12060799
TI  - Dopamine D2 receptors internalize in their low-affinity state.
AB  - The present study was done in order to determine whether dopamine internalizes D2
      receptors in CHO cells and whether the high-affinity or the low-affinity state of
      the dopamine D2 receptor is associated with dopamine-induced internalization of
      dopamine D2 receptors. Using [3H]sulpiride to label D2Long receptors in CHO
      cells, it was found that dopamine lowered the binding of [3H]sulpiride by 20%.
      Although the high-affinity states of D2 were converted to low-affinity states by
      guanine nucleotide, the latter had no effect in blocking the dopamine-induced
      reduction in [3H]sulpiride binding, indicating that the dopamine-induced
      internalization of D2 receptors occurred with D2 in the low-affinity state.

PMID- 12060800
TI  - Automatic grapheme processing in the left occipitotemporal cortex.
AB  - In a previous event-related fMRI study, we showed that the left occipitotemporal
      cortex was specifically involved in the abstract categorization of visually
      presented alphabetic symbols. Here, we duplicate the fMRI study by measuring
      visual event-related potentials to verify whether the left posterior cortex
      supports the processing of graphemic representations at a perceptual, prelexical
      level. N170 amplitudes elicited by the categorically ambiguous stimulus 'O' were
      about twice as small in the left as in the right occipitotemporal region, and
      comparable to that of other letters on the left, and to that of other geometric
      figures on the right. The side asymmetry suggests that a graphemic module is
      unilaterally implemented in the left hemisphere, where it automatically processes
      heteromorphic representations that do not depend on the physical characteristics
      of the signal, whereas the difference in amplitude suggests that this left
      graphemic module is in series with, precedes and does not transmit information
      to, or inhibits a general shape-analysis module.

PMID- 12060801
TI  - Defective somatic markers in sub-clinical psychopathy.
AB  - Damasio's somatic marker hypothesis is argued to be specifically applicable to
      psychopathy, though evidence has been meager until now. The principal evidence
      for the somatic marker hypothesis is based on findings in patients with
      orbitofrontal lesions, showing absent punishment learning on the Iowa gambling
      task. Interestingly, neuroimaging studies indicate orbitofrontal dysfunction in
      psychopathy also. Here we investigated the somatic marker hypothesis in subjects
      selected on low and high psychopathic behavioral characteristics from the outer
      extreme ranges of a large subject pool (n = 525). The low psychopathic subject
      group (n = 16) showed intact punishment learning, suggesting somatic markers came
      to guide their decisions in the course of the game. In contrast, such punishment
      learning was not observed in the high psychopathic subject group (n = 16), who
      mimicked the gambling behavior of orbitofrontal patients. These findings provide
      further evidence for the hypothesized link between psychopathy and orbitofrontal
      dysfunction.

PMID- 12060802
TI  - Refractive compensation to optical defocus depends on the temporal profile of
      luminance modulation of the environment.
AB  - The refractive state of hatchling chicks rapidly compensates to applied optical
      defocus through alteration in eye growth. The mechanism is capable of sensing
      whether the plane of focus lies in front of or behind the photoreceptors,
      however, its nature and site of action within the retina are unknown. We
      attempted to create an imbalance in the adaptation of the retinal ON and OFF
      mechanisms previously implicated in refractive control through pharmacological
      interventions, by rearing chicks from 4 to 9 days of age with a monocular +10 D,
      0 D or -10 D lens, in an environment illuminated by a moving or stationary plaid
      of luminance gradients. When the plaid moved in one direction a local Fast-ON
      sawtooth luminance modulation was produced, while plaid motion in the other
      direction resulted in a Fast-OFF sawtooth modulation. Significantly reduced
      refractive compensation accompanied +10 D lens/Fast-OFF and -10 D lens/Fast-ON
      rearing, but not for the other conditions. Thus the refractive compensation
      mechanism depends on the nature of the temporal contrast of the environment,
      suggesting a relationship between the sign of defocus and the state of adaptation
      of the retinal ON and OFF subsystems.

PMID- 12060803
TI  - Response characteristics of nasal trigeminal nociceptors in Gallus domesticus.
AB  - Although the chemoreceptive properties of the nasal trigeminal system are well
      known, the physiological characteristics of nasal nociceptors responding to both
      mechanical and chemical stimulation have not been well described. In this study,
      the activity of single nasal trigeminal units recorded from microdissected twigs
      of the ethmoidal nerve of anaesthetized hens (Gallus domesticus) was
      investigated. Using a mechanical search stimulus, 20 slowly and 22 rapidly
      adapting nasal mechanoreceptors were identified, exhibiting mean thresholds of
      2.96 g. Twelve slowly adapting units also exhibited chemical sensitivity when
      exposed to ammonia gas. These had mean response thresholds of 0.232% vapour
      saturation and exhibited variable stimulus-response profiles. This is the first
      study to quantify the responses of polymodal nasal nociceptors to a noxious
      airborne chemical in any species.

PMID- 12060804
TI  - Diversity of Kir channel subunit mRNA expressed by retinal glial cells of the
      guinea-pig.
AB  - One of the main functions of Muller glial cells is the performance of retinal K+
      homeostasis which is thought to be primarily mediated by K+ fluxes through
      inwardly rectifying K+ (Kir) channels expressed in Muller cell membranes. Until
      now, there is limited knowledge about the types of Kir channel subunits expressed
      by Muller cells. Using RT-PCR, we investigated the expression of mRNA encoding
      different Kir channel subunits in the retina of the guinea pig. In order to
      verify expression by Muller cells, primary cultures of guinea pig Muller cells
      were also investigated. Both retinae and cultured Muller cells express mRNA for a
      diversity of Kir channel subtypes which include members of at least four channel
      subfamilies: Kir2.1, Kir2.2, Kir2.4, Kir3.1, Kir 3.2, Kir4.1, Kir6.1, and Kir6.2.
      mRNAs for the following Kir channel subtypes were not detected in Muller cells:
      Kir1.1, Kir2.3, Kir3.3, Kir3.4, Kir4.2, and Kir5.1. It is concluded that the
      spatial buffering of extracellular K+ by Muller cells may be mediated by
      cooperation of different subtypes of Kir channels, and that the distinct Kir
      channel types involved in this function may change depending on the physiological
      or metabolic state of the retina.

PMID- 12060805
TI  - Expression of tenascin-C long isoforms is induced in the hypothalamus by FGF-1.
AB  - Fibroblast growth factor (FGF)-1 modulates various brain functions, such as the
      hypothalamic control of feeding. In the rat, we examined the effect of
      intracerebroventricularly infused FGF-1 on the hypothalamic expression of
      tenascin-C, a selective mediator of neuron-glial interaction. In situ
      hybridization revealed little tenascin-C mRNA expression in control brains, but
      greatly increased expression in ependymal cells around the third ventricle in the
      FGF-1-infused rats. Reverse transcription-linked PCR analysis of hypothalamic
      mRNA revealed an FGF-1-induced expression not of the shortest isoform of tenascin
      C, but of the long isoforms (with additional fibronectin type III-domain
      insertions). Quantitative analysis by real time PCR revealed that this induction
      was transient and dose-dependent. Specific modulation of hypothalamic neuron
      glial interactions by tenascin-C may mediate FGF-1-induced feeding suppression.

PMID- 12060806
TI  - Neuropathy reduces viscero-somatic inhibition via segmental mechanisms in rats.
AB  - The effect of an experimental neuropathy on the viscero-somatic inhibition was
      studied in lightly anesthetized rats. In controls, colo-rectal distension at
      noxious intensities produced a multisegmental prolongation of the withdrawal
      response induced by noxious stimulation of the skin. In rats with a spinal nerve
      ligation induced neuropathy this viscero-somatic inhibition was significantly
      reduced within the neuropathic segment (the hindlimb) but not outside of it (the
      tail). Naloxone, an opioid antagonist, attenuated this viscero-somatic inhibition
      in controls and it did not restore the inhibition in neuropathic rats. The
      results indicate that somatic neuropathy produces a segmental attenuation of
      viscero-somatic inhibition and this attenuation cannot be explained by a nerve
      injury-induced release of endogenous opioids. The decreased inhibition of somatic
      signals may contribute to the hypersensitivity observed in neuropathic
      conditions.

PMID- 12060807
TI  - Glutamate-induced increases in intracellular Ca2+ in cultured rat neocortical
      neurons.
AB  - In neurons, changes in intracellular Ca2+ concentration ([Ca2+]i) trigger
      neurotransmitter release, regulate membrane excitability, affect gene expression,
      and govern short- and long-term forms of synaptic plasticity. Rises in
      cytoplasmic Ca2+ are thought to underlie the various effects of glutamatergic
      neurotransmitters within the central nervous system. In the present study, we
      applied a calcium imaging technique using a confocal laser scanning microscope to
      investigate the effects of excitatory amino acids on glutamate induced calcium
      influx in primary cultured neocortical neurons. Glutamate (5 microM) induced
      increases in [Ca2+]i in both the soma and dendritic processes of the cells. The
      increase was partially blocked by 10 microM DL-2-amino-5-phosphovaleric acid
      (APV), a NMDA antagonist. The reduction was higher in the dendritic process than
      in the cell body: the reduction was 58% in the cell body and 67% in the dendritic
      processes. In contrast, 5 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a
      non-NMDA antagonist, had less effect on the response. We observed an 11%
      reduction in the dendritic processes, but no change in the cell bodies. The
      results demonstrated the heterogeneous distribution of APV- and CNQX-sensitive
      channels in primary cultured neocortical neurons. In both the cell body and
      dendritic processes, [Ca2+]i increase induced by low concentrations of glutamate
      was mainly due to the activation of NMDA receptors.

PMID- 12060808
TI  - The spin trapping agent PBN stimulates H2 O2 -induced Erk and Src kinase activity
      in human neuroblastoma cells.
AB  - The spin-trap, alpha-phenyl-N-tert-butylnitrone (PBN) has been shown to have
      neuroprotective properties and may prevent oxidative injury in vivo and in
      cultured cells. Although PBN quenches reactive oxygen species, the direct
      mechanism of neuroprotective action is unknown. In the present study, we examined
      the effects of PBN on the regulation of the mitogen activated kinase Erk and as
      well as Src family tyrosine kinases, enzymes known to be activated by oxygen
      species such as H2O2. In SH-SY5Y human neuroblastoma cells, H2O2 induced
      activation of Erk and Src kinases was markedly potentiated by treatment with PBN.
      The potentiation by PBN of the Erk and Src kinase activation by H2O2 required
      extracellular Ca2+ and appeared dependent on voltage sensitive Ca2+ channels. In
      contrast, PBN did not affect depolarization-dependent or growth factor-dependent
      Erk and Src kinase phosphorylation. Our results suggest that PBN might have a
      protective effect on cells by potentiating the anti-apoptotic Erk and Src kinase
      pathways responding to H2O2, an effect apparently distinct from its ability to
      trap oxygen free radicals.

PMID- 12060809
TI  - Short-term hypobaric hypoxia enhances visual contrast sensitivity.
AB  - The effect of hypoxia on early visual functions remains a controversial area of
      research. To explore this question, we measured static and dynamic visual
      contrast sensitivity in 14 healthy volunteers at a simulated altitude of 5500 m.
      In comparison with the baseline condition (mean arterial oxygen saturation:
      98.4%), contrast sensitivity significantly increased after 5, 10 and 15 min of
      hypoxic exposure (saturation: 82.9%, 77.0%, 74.3%, respectively). After 10 min,
      this enhancement was markedly pronounced under dynamic conditions. Returning to
      the baseline altitude (saturation: 97.7%), contrast sensitivity recovered, mostly
      at the lower spatial frequencies. There was a significant negative relationship
      between arterial oxygen saturation and contrast sensitivity values at low and
      medium spatial frequencies (0.5-4.8 c/deg). These results suggest that early
      visual processing may be enhanced during short-term hypoxic challenge.

PMID- 12060810
TI  - Minocycline delays disease onset and mortality in a transgenic model of ALS.
AB  - Microglial activation is thought to contribute to the progression of selective
      motor neuron death during amyotrophic lateral sclerosis (ALS). As minocycline has
      been shown to inhibit microglial activation, the therapeutic efficacy of this
      tetracycline derivative in the G93A mice model for familial ALS was tested. This
      drug with proven safety delayed disease onset and dose-dependently extended the
      survival of the G93A mice. At 120 days of age, minocycline protected mice from
      loss of motor neurons and from vacuolization. These results demonstrate that
      interference with immuno-inflammatory responses has a beneficial effect in the
      ALS mice model, suggesting this to be a potential new strategy to treat ALS.

PMID- 12060811
TI  - Development of the regenerative capacity of postnatal axotomized rat spinal
      motoneurons.
AB  - The present study examined whether a peripheral nerve (PN) graft can rescue
      developing motoneurons from degeneration and determined when immature motoneurons
      begin to express a regenerative capacity. Transplantation of a PN graft was
      unable to rescue motoneurons from degeneration if spinal root avulsion was
      performed in animals younger than P14. However, this procedure did enhance
      motoneuron survival when root avulsion was performed at P14 or later. Immature
      (P1 or P7) motoneurons were unable to regenerate their axons into the
      transplanted PN graft following root avulsion, whereas in older animals (P14-P28)
      motoneurons were able to regenerate axons into the PN graft. The percentage of
      regenerated motoneurons increased from P21 to P28 and was similar to that of
      adult animals. Therefore, the regenerative capacity of rat spinal motoneurons
      first begins at about P14, which seems to be critical.

PMID- 12060812
TI  - Language-impaired children: No sign of the FOXP2 mutation.
AB  - A mutation in the FOXP2 gene has been found to be responsible for the autosomal
      dominant inheritance of a severe form of speech and language impairment in a
      family known as KE. We genotyped the FOXP2 mutation for 270 4-year-old children
      selected for low general language scores from a representative community sample
      of more than 18,000 children. No language-impaired child had the FOXP2 mutation.
      Although rare severe disorders such as those of the KE family are often caused by
      a single gene, common disorders such as language impairment are more likely to be
      the quantitative extreme of the same multiple genetic factors responsible for
      heritability throughout the distribution.

PMID- 12060813
TI  - Event-related potentials reflect individual differences in age-invariant auditory
      skills.
AB  - Previous work has found that auditory event-related potentials show maturational
      changes, with latency and amplitude of late components (N1 and P2) decreasing and
      increasing with age respectively. Our goal was to test the hypothesis that these
      changes reflect increased speed of neural processing in the auditory system.
      Thirty-three listeners, aged 10-50 years, were tested on a frequency
      discrimination task and an auditory backward recognition masking task. P1 and N1b
      event-related potential components were measured to tones. The N1b became larger
      and earlier with age, and the latency of P1 decreased with age. However,
      thresholds on the behavioural tasks did not change with age. Nevertheless,
      individual differences in the peak amplitude of N1b were independently related to
      frequency discrimination and degree of masking. Thus, the relationship that does
      exist between individual differences in psychoacoustic performance and the
      auditory N1b reflect a stable characteristic of the individual rather than a
      maturational change.

PMID- 12060814
TI  - Polyamine uptake is necessary for a normal biochemical maturation of astrocytes
      in culture.
AB  - In this study we have explored the importance of polyamine uptake in the
      proliferation and biochemical maturation of cerebellar astroyctes in culture. The
      uptake of polyamines paralleled astrocyte proliferation measured as [3H]thymidine
      incorporation into the DNA. Inhibition of polyamine uptake did not alter the
      developmental profile of thymidine incorporation, perhaps due to a compensatory
      increase in ornithine decarboxylase activity but was able to reduce glutamine
      synthetase (GS) activity, an enzymatic marker for astrocyte biochemical
      maturation, from 9 days in vitro. The present results suggest that polyamine
      uptake plays an important role in the biochemical maturation of astrocytes in
      culture.

PMID- 12060816
TI  - Progress in oncology.

PMID- 12060815
TI  - Evoked intracellular Ca2+ elevations in HT4 neuroblastoma cells.
AB  - In this study, membrane depolarization and multiple neurotransmitters (5-HT,
      acetylcholine, histamine, norepinephrine, epinephrine, glutamate, and ATP) were
      tested for the ability to elevate the intracellular free Ca2+ concentration
      ([Ca2+]i) in mouse HT4 neuroblastoma cells. Apart from ATP, none of the
      treatments gave rise to a detectable Ca2+ response, no matter whether the cells
      were subjected to temperature-induced neuronal differentiation. Our results
      provide pharmacological evidence for the co-existence in HT4 cells of both P2X
      and P2Y receptors, the activation of which by ATP led to Ca2+ influx and Ca2+
      release, respectively. The P2Y receptor was found to couple to more than one type
      of G protein in the signaling pathway, causing the activation of phospholipase C
      (PLC) and Ca2+ mobilization from intracellular stores. cAMP-dependent protein
      kinase (PKA) and protein kinase C (PKC) attenuated ATP-evoked [Ca2+]i elevations
      in different ways. However, no correlation was identified between neuronal
      differentiation and the ATP-evoked Ca2+ responses in HT4 cells. This work
      indicates that HT4 cells can serve as a good model to study P2 purinoceptor
      associated signaling pathways.

PMID- 12060817
TI  - Lymphatic mapping in solid neoplasms: state of the art.
AB  - BACKGROUND: Lymphatic mapping and sentinel lymph node biopsy is an established
      technique for the staging and treatment of melanoma. The success of lymphatic
      mapping in this realm has broadened its application to other solid neoplasms.
      This update reviews the status of sentinel lymph node biopsy in its most widely
      cited applications. METHODS: Seminal manuscripts on lymphatic mapping in
      melanoma, breast, colon, vulvar, cervical, lung, gastric, and head and neck
      cancers are reviewed. RESULTS: Studies suggest that the application of lymphatic
      mapping as a staging tool in breast cancer and melanoma is justified when applied
      by trained surgeons. Additional validation is necessary before sentinel node
      biopsy is advocated in gynecologic, colon, lung, and head and neck cancer.
      CONCLUSIONS: As in breast cancer and melanoma, validation of the sentinel node
      concept in other solid tumors must occur in institutions other than those in
      which the technique is being developed before it is generally applied to other
      neoplasms.

PMID- 12060819
TI  - Hypopituitarism in childhood.
AB  - BACKGROUND: Childhood hypopituitarism may be present at birth or may be acquired.
      Early diagnosis and treatment promote the best possible outcomes. METHODS: The
      anatomy, etiologies, clinical presentation, diagnostic testing strategies, and
      current treatments relevant to childhood hypopituitarism are reviewed. RESULTS:
      Children with congenital hypopituitarism may present with life-threatening
      hypoglycemia, abnormal serum sodium concentrations, shock, microphallus in males,
      and, only later, growth failure. Causes of congenital hypopituitarism include
      septo-optic dysplasia, other midline syndromes, and mutations of transcription
      factors involved in pituitary gland development. Children with acquired
      hypopituitarism typically present with growth failure and may have other
      complaints depending on the etiology and the extent of missing pituitary
      hormones. Acquired hypopituitarism may result from tumors (most commonly
      craniopharyngioma), radiation, infection, hydrocephalus, vascular anomalies, and
      trauma. CONCLUSIONS: An MRI of the head is critical in determining the etiology.
      Testing for pituitary hormone deficiencies is undertaken along with appropriate
      hormonal replacement and, in some cases, direct treatment of the cause of the
      hypopituitarism. All children with hypopituitarism require coordination of
      medical care by a pediatric endocrinologist and, when older, transition to the
      care of an internist endocrinologist. Referrals to a reproductive endocrinologist
      may be required as fertility issues arise.

PMID- 12060818
TI  - Impact of age and colony-stimulating factor use on hospital length of stay for
      febrile neutropenia in CHOP-treated non-Hodgkin's lymphoma.
AB  - BACKGROUND: In intermediate-grade non-Hodgkin's lymphoma (NHL) patients, full
      dose CHOP improves survival but increases myelosuppression, causing febrile
      neutropenia hospitalization (FNH) in 28% of patients 65 years of age or greater.
      Several risk factors for FNH are known, but their relationship to length of stay
      (LOS), an indicator of the total burden of FNH, is unclear. METHODS: We conducted
      a study to identify factors associated with the incidence, recurrence, and
      duration of hospitalizations for FN and to describe the frequency of
      administration of colony-stimulating factor (CSF) as primary and secondary
      prophylaxis and its association with repeated hospitalization episodes. RESULTS:
      Compared with patients who did not experience hospitalizations for FN, those who
      did were significantly older, had more comorbid conditions, were planned for
      standard dose intensity, and received CSF less often during the first 5 days of
      cycle 1 (early CSF). Overall, 73% of these hospitalizations occurred within the
      first 2 cycles of chemotherapy, with 56% occurring within the first cycle.
      Patients age > or = 65 years accounted for 66% of cycle 1 FNH. Patients receiving
      early CSF were less likely to experience repeated hospitalizations (0% vs 12%;
      P<.05). Multiple regression analysis of those hospitalized found a 3.9-day longer
      LOS for patients age > or = 65 years and a 5.13-day longer LOS for those not
      receiving early CSF. CONCLUSIONS: Older NHL patients have a higher risk of
      hospitalization for FN and longer LOS. The majority of hospitalization days occur
      in the first 2 cycles of chemotherapy. Early CSF use is associated with decreased
      risk of repeated hospitalizations and shorter total LOS. Secondary CSF use is
      also associated with reduced risk of repeated FNH.

PMID- 12060820
TI  - Microscopic paraseptal sphenoidotomy approach for pituitary tumors.
AB  - BACKGROUND: Dissection of mucosa from the nasal septum during a transsphenoidal
      approach may lead to significant morbidity. Endoscopic techniques that obviate
      this dissection and its complications have been successful for pituitary
      operations. These techniques, however, are generally not stereoscopic, can add
      significant costs, and in many instances require additional surgical personnel.
      METHODS: We have exposed 11 sella lesions with the operating microscope without
      intranasal dissection or use of endoscopy. A paraseptal approach was utilized by
      following the middle turbinate to the nasopharynx and performing a bilateral
      sphenoidotomy. RESULTS: Of the 11 sella lesions addressed through this approach,
      6 were macroadenomas (2 secreting and 4 nonsecreting), 1 was a craniopharyngioma,
      1 was a Rathke's cleft cyst, and 2 were cerebrospinal fluid leaks into the
      sphenoid sinus. In 1 case, an ectopic pituitary adenoma was biopsied. Subtotal or
      near total tumor resection or successful repair of cerebrospinal fluid leaks was
      achieved. In all cases, the exposure was satisfactory. A fat graft was used in 6
      cases. Postoperatively, no nasal packing was used and there were no nasal
      complications. Vision improved in all 5 cases with preoperative visual
      impairment. Complications included diabetes insipidus (1), impaired taste (1),
      and delirium tremens (1), all of which were transient. CONCLUSIONS: Microscopic
      sphenoidotomy is a safe and effective alternative to traditional transseptal or
      endoscopic exposures of the sella.

PMID- 12060821
TI  - Use of complementary/integrative nutritional therapies during cancer treatment:
      implications in clinical practice.
AB  - BACKGROUND: The objectives of this study were to determine the prevalence and
      characterize the use of complementary/integrative nutritional therapies (CINTs)
      by patients during cancer treatment. METHODS: This retrospective review used data
      collected as a part of standard clinical care provided by the registered clinical
      dietitians and included nutritional history, demographic variables,
      anthropometrics, prevalence of use, and the specific integrative nutritional
      therapies used by these patients during cancer treatment. RESULTS: Twenty-nine
      percent of 820 patients reported use of CINTs not prescribed by their physician.
      Caucasians and patients over age 60 were the principal users of CINTs during
      treatment. Modular vitamins were the most frequently reported additive (86.9%),
      followed by botanicals/biologics (43.8%) and mineral supplements (28.6%).
      CONCLUSIONS: A considerable proportion of cancer patients use unproven CINTs
      during cancer treatment. The health professional should become more aware of the
      complementary/integrative therapies that their patients are using during cancer
      treatment.

PMID- 12060823
TI  - Evaluation of bone metastases in lung cancer. Improved sensitivity and
      specificity of PET over bone scanning.

PMID- 12060822
TI  - Fulminant hepatic failure due to disseminated adenovirus infection in a patient
      with chronic lymphocytic leukemia.

PMID- 12060824
TI  - Malignant localized fibrous tumor of the pleura.

PMID- 12060825
TI  - Cardiovascular effects of psychotropic drugs.

PMID- 12060828
TI  - Goitrogenic and estrogenic activity of soy isoflavones.
AB  - Soy is known to produce estrogenic isoflavones. Here, we briefly review the
      evidence for binding of isoflavones to the estrogen receptor, in vivo
      estrogenicity and developmental toxicity, and estrogen developmental
      carcinogenesis in rats. Genistein, the major soy isoflavone, also has a frank
      estrogenic effect in women. We then focus on evidence from animal and human
      studies suggesting a link between soy consumption and goiter, an activity
      independent of estrogenicity. Iodine deficiency greatly increases soy antithyroid
      effects, whereas iodine supplementation is protective. Thus, soy effects on the
      thyroid involve the critical relationship between iodine status and thyroid
      function. In rats consuming genistein-fortified diets, genistein was measured in
      the thyroid at levels that produced dose-dependent and significant inactivation
      of rat and human thyroid peroxidase (TPO) in vitro. Furthermore, rat TPO activity
      was dose-dependently reduced by up to 80%. Although these effects are clear and
      reproducible, other measures of thyroid function in vivo (serum levels of
      triiodothyronine, thyroxine, and thyroid-stimulating hormone; thyroid weight; and
      thyroid histopathology) were all normal. Additional factors appear necessary for
      soy to cause overt thyroid toxicity. These clearly include iodine deficiency but
      may also include additional soy components, other defects of hormone synthesis,
      or additional goitrogenic dietary factors. Although safety testing of natural
      products, including soy products, is not required, the possibility that widely
      consumed soy products may cause harm in the human population via either or both
      estrogenic and goitrogenic activities is of concern. Rigorous, high-quality
      experimental and human research into soy toxicity is the best way to address
      these concerns. Similar studies in wildlife populations are also appropriate.

PMID- 12060827
TI  - A model of the development of the brain as a construct of the thyroid system.
AB  - Thyroid hormone is essential for normal brain development. However, little is
      known about the molecular and cellular mechanisms that mediate thyroid hormone
      action on the developing brain or the developmental events selectively affected.
      Consequently, although a large number of environmental chemicals interfere with
      the thyroid system, there are few neurodevelopmental end points to recruit for
      toxicological studies. Therefore, my goal here is to review what is known about
      the relative timing of normal brain construction and thyroid system development,
      with special focus on the period of in utero development in humans and the
      comparable developmental period in laboratory rats. These data are presented as a
      timeline to aid in the identification of thyroid-sensitive end points in brain
      development and to highlight important data gaps. I discuss the known influence
      of certain synthetic chemicals on the thyroid system and include a brief review
      of the effects of developmental exposure to chemicals on thyroid system function.
      The relationship between the thyroid hormone and retinoic acid systems, as well
      as the thyroid hormone sensitivity of the developing cochlea, is also discussed.

PMID- 12060830
TI  - Clues from wildlife to create an assay for thyroid system disruption.
AB  - In 1996 the U.S. Congress charged the U.S. Environmental Protection Agency to
      develop a screening program to test chemicals for their possible estrogenic and
      other endocrine effects. Shortly thereafter, the Chemical Guidelines Program of
      the Organisation for Economic Co-operation and Development's (OECD) Environmental
      Directorate organized a Task Force on Endocrine Disruption Testing and Assessment
      to coordinate development of internationally harmonized screening and testing
      protocols. Most of the research devoted to this effort has focused on detecting
      impaired estrogenicity, androgenicity, and/or steroidogenesis, with little
      progress toward developing assays to detect chemicals that might interfere with
      thyroid function. Despite the fact that wildlife biologists have been reporting
      abnormal thyroid gland development and unusual thyroid hormone (TH) and retinoid
      ratios in fish and birds since the early 1960s, few studies have demonstrated an
      association between an environmental contaminant and a particular health end
      point other than reduced reproductive success at the population level. This
      article is a review of the literature that specifically examines THs and their
      role in normal behavior and development in wildlife. It presents several studies
      that associated changes in the thyroid gland, TH concentrations, and behavior
      with contaminant exposure. The goal of this article is to provide fodder for the
      creation of simple screens to detect possible thyroid system agonists and
      antagonists.

PMID- 12060829
TI  - Thyroid hormone, brain development, and the environment.
AB  - Thyroid hormone is essential for normal brain development. Therefore, it is a
      genuine concern that thyroid function can be altered by a very large number of
      chemicals routinely found in the environment and in samples of human and wildlife
      tissues. These chemicals range from natural to manufactured compounds. They can
      produce thyroid dysfunction when they are absent from the diet, as in the case of
      iodine, or when they are present in the diet, as in the case of thionamides.
      Recent clinical evidence strongly suggests that brain development is much more
      sensitive to thyroid hormone excess or deficit than previously believed. In
      addition, recent experimental research provides new insight into the
      developmental processes affected by thyroid hormone. Based on the authors'
      research focusing on the ability of polychlorinated biphenyls to alter the
      expression of thyroid hormone-responsive genes in the developing brain, this
      review provides background information supporting a new way of approaching risk
      analysis of thyroid disruptors.

PMID- 12060831
TI  - Evidence that GABAergic neurons in the preoptic area of the rat brain are targets
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin during development.
AB  - Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes
      with masculinization and defeminization of male sexual behaviors and gonadotropin
      release patterns. We previously demonstrated that the mRNA encoding the
      arylhydrocarbon receptor (AhR), a protein that mediates TCDD effects, is found in
      brain regions that control reproductive functions, most notably in the preoptic
      area (POA). The pattern of distribution of the AhR gene closely overlaps that of
      an enzyme necessary for Gamma-aminobutyric acid (GABA) synthesis, glutamic acid
      decarboxylase (GAD) 67. To test the hypothesis that GABAergic neurons in the POA
      are targets of TCDD during development, we used dual-label in situ hybridization
      histochemistry (ISHH) to co-localize GAD and AhR mRNAs in the region. In
      addition, we used ISHH to determine the effects of TCDD (1 microg/kg body weight,
      gestational day 15) on GAD 67 gene expression in POA regions in pups examined on
      postnatal day 3. We found that virtually all GABAergic neurons in the POA
      expressed the AhR gene. Furthermore, GAD 67 mRNA levels were higher in females
      than in males in the rostral POA/anteroventral periventricular nucleus
      (rPOA/AVPV) and in the rostral portion of the medial preoptic nucleus (MPN). TCDD
      abolished sex differences in the rPOA/AVPV but had no effect in the rostral MPN.
      In the caudal MPN, there were no sex differences in GAD 67 gene expression, but
      TCDD depressed expression specifically in males. Our findings demonstrate that
      GABAergic neurons in the brain are targets of TCDD and may mediate developmental
      effects of this contaminant on reproductive function.

PMID- 12060833
TI  - Sexually dimorphic nonreproductive behaviors as indicators of endocrine
      disruption.
AB  - Measures of cognitive and other behaviors not specifically related to
      reproduction are often sex-linked. Males and females perform differently on many
      tasks and often interact with members of their species in dissimilar ways. If
      such differences are diminished, reversed, or widened by prenatal chemical
      exposures, a reasonable inference is that exposure interfered with sexual
      differentiation of the brain, largely, but not exclusively, through interference
      with the actions of gonadal hormones. Explicit recognition of sex differences in
      performance is not a prominent feature of toxicity testing, however, except for
      reproduction studies, and is not a recognized criterion in developmental
      neurotoxicity testing. In contrast to the low visibility accorded sex differences
      in testing protocols for the assessment of developmental neurotoxicity, the
      literature is filled with examples showing that the developing male and female
      respond differently to many chemical agents, with subsequent expression in
      behavior. Quite often, even when such differences are reported, further analyses
      are not carried out nor are subsequent studies conducted for clarification.
      Moreover, many investigators include only male subjects. Both polychlorinated
      biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) studies provide several
      examples of striking differences between the behavioral responses of male and
      female offspring to developmental exposure. They offer examples, as well, of how
      to approach the study and analysis of such differences. Given the societal
      importance of risk assessments applied to potential developmental neurotoxicants,
      studies should be deemed questionable if they fail to include outcome measures
      based on sexual dimorphisms in nonreproductive behaviors.

PMID- 12060834
TI  - Effects of incubation temperature and estrogen exposure on aromatase activity in
      the brain and gonads of embryonic alligators.
AB  - During embryogenesis, incubation temperature and the hormonal environment
      influence gonadal differentiation of some reptiles, including all crocodilians.
      Current evidence suggests that aromatase, the enzyme that converts androgens to
      estrogens, has a role in sexual differentiation of species that exhibit
      temperature-dependent sex determination (TSD). During the temperature-sensitive
      period (TSP) of sex determination, we compared aromatase activity in the brain
      and gonads of putative male and female alligator embryos to determine if
      aromatase activity in the embryonic brain could provide the hormonal environment
      necessary for ovarian development in a TSD species. In addition, we assessed the
      pattern of aromatase activity in the brain and gonads of embryos treated with
      estradiol-17beta (E(2)) and incubated at male-producing temperatures to compare
      enzyme activity in E(2) sex-reversed females to control males and females. This
      has particular significance regarding wildlife species living in areas
      contaminated with suspected environmental estrogens. Gonadal aromatase activity
      remained low during the early stages of the TSP in both sexes and increased late
      in the TSP only in females. Aromatase activity in the brain increased prior to
      gonadal differentiation in both sexes. These results suggest that aromatase
      activity in the brain is not directly responsible for mediating differentiation
      of the gonad. E(2) exposure at male-producing temperatures resulted in sex
      reversed females that had intermediate gonad function and masculinized brain
      activity. This study indicates the need to examine multiple end points and to
      determine the persistence of developmental alterations in contaminant-exposed
      wildlife populations.

PMID- 12060832
TI  - Electrophysiologic and behavioral effects of perinatal and acute exposure of rats
      to lead and polychlorinated biphenyls.
AB  - Lead and polychlorinated biphenyls (PCBs) both cause a reduction of intelligence
      quotient and behavioral abnormalities in exposed children that have features in
      common with attention deficit hyperactivity disorder. We have used rats as a
      model to study the effects of both perinatal and acute exposure to lead or PCBs
      in an effort to compare and understand the mechanisms of these nervous system
      decrements. Long-term potentiation (LTP) is an electrophysiologic measurement
      that correlates well with cognitive ability. We have determined the effects of
      chronic perinatal exposure to lead or PCB 153 as well as acute application of
      these substances to isolated brain slices, with recordings in two areas of the
      hippocampus, CA1 and CA3. Both substances, whether chronically or acutely
      applied, significantly reduced LTP in CA1 in animals at age 30 and 60 days. In
      CA3, they reduced LTP in 30-day animals but potentiated it in 60-day animals.
      Although neither lead nor PCB 153 alters baseline synaptic transmission at low
      stimulus strengths, at higher levels they induce changes in the same direction as
      those of LTP. These results show surprisingly similar actions of these quite
      different chemicals, and the similarity of effects on chronic and acute
      application indicates that effects are both pharmacologic and developmental.
      Behavioral studies of rats exposed to PCBs from contaminated fish show
      hyperactivity, impulsiveness, and increased frustration relative to unexposed
      controls. These results demonstrate that lead and PCBs have similar effects on
      synaptic plasticity and behavior and suggest that the compounds may act through a
      common mechanism.

PMID- 12060836
TI  - Effects of perinatal exposure to bisphenol A on play behavior of female and male
      juvenile rats.
AB  - In higher vertebrates, estrogen can exert an organizational effect on sexually
      dimorphic areas of the central nervous system (CNS) during the perinatal phase of
      development. The possibility that estrogenic pollutants may mimic estrogen action
      on the CNS during development and produce long-lasting or irreversible effects is
      an issue of great concern. Bisphenol A (BPA), a compound widely used in the food
      industry and in dentistry, has proven estrogenic actions. To study its potential
      developmental effects on behavior, we gave female Sprague-Dawley rats 40
      microg/kg/day BPA from conception to weaning postnatal day 21 and 400
      microg/kg/day BPA from gestation day 14 to postnatal day 6. After exposure, we
      studied social behavior in a play situation in juvenile male and female
      offspring. The attempt to use play behavior to study the effects of BPA yielded
      some interesting results. We observed an early action of BPA on several
      behavioral categories in both males and females. In particular we observed a
      masculinization of female behavior in two behavioral categories (play with
      females and sociosexual exploration), an effect probably mediated by the
      estrogenic activity of BPA in the CNS. These long-lasting effects of BPA could
      have important consequences at individual and population levels.

PMID- 12060835
TI  - Early cerebral activities of the environmental estrogen bisphenol A appear to act
      via the somatostatin receptor subtype sst(2).
AB  - Recently, considerable interest has been aroused by the specific actions of
      bisphenol A (BPA). The present investigation represents a first study dealing
      with the interaction of BPA with the biologically more active somatostatin
      receptor subtype (sst(2)) in the rat limbic circuit. After treating pregnant
      female Sprague-Dawley rats with two doses (400 microg/kg/day; 40 microg/kg/day)
      of BPA, the binding activity of the above receptor subtype was evaluated in some
      limbic regions of the offspring. The higher dose proved to be the more effective
      one, as demonstrated by the elevated affinity of sst(2) with its specific
      radioligand, [(125)I]-Tyr(0)somatostatin-14. The most dramatic effects of BPA on
      sst(2) levels occurred at the low-affinity states of such a subtype in some
      telencephalic limbic areas of postnatal rats (10 days of age; postnatal day [PND]
      10). These included lower (p < 0.05) sst(2) levels in the gyrus dentate of the
      hippocampus and basomedial nucleus of the amygdala; significantly higher (p <
      0.01) levels were observed only for the high-affinity states of the
      periventricular nucleus of the hypothalamus. A similar trend was maintained in
      PND 23 rats with the exception of much lower levels of the high-affinity sst(2)
      receptor subtype in the amygdala nucleus and ventromedial hypothalamic nucleus.
      However, greater changes produced by this environmental estrogen were reported
      when the binding activity of sst(2) was checked in the presence of the two more
      important selective agonists (zolpidem and Ro 15-4513) specific for the alpha
      containing Gamma-aminobutyric acid (GABA) type A receptor complex. In this case,
      an even greater potentiating effect (p < 0.001) was mainly obtained for the low
      affinity sst(2) receptor subtype in PND 10 animals, with the exception of the
      high-affinity type in the ventromedial hypothalamic nucleus and gyrus dentate.
      These results support the contention that an sst(2) subtype alpha-containing GABA
      type A receptor system might represent an important neuromediating station
      capable of promoting estrogenlike mechanisms of BPA, especially during the early
      developmental phases.

PMID- 12060837
TI  - Effects of perinatal exposure to bisphenol A on sociosexual behavior of female
      and male rats.
AB  - Perinatal action of estrogens or aromatizable steroids at the central nervous
      system level is responsible for brain sexual differentiation. Through early
      contact with the central nervous system, the estrogenic compound bisphenol A
      (BPA) could alter the processes affecting sociosexual behavior. To test this
      hypothesis, we studied agonistic and sexual behavior of adult female and male
      rats whose mothers were administered BPA (40 microg/kg/day) during pregnancy or
      lactation. An intruder test revealed in males but not in females an increase in
      defensive behavior due to BPA. We studied the effect of BPA on sexual behavior by
      testing sexual orientation and sexual activity. Male sexual orientation toward a
      stimulus female was not affected by BPA, whereas the sexual activity test
      revealed a slight impairment of sexual performance due to BPA in terms of latency
      and frequency of intromissions. In females, BPA produced a small increase in
      sexual motivation and receptive behavior. In conclusion, BPA administration, both
      during pregnancy and during lactation, does not masculinize female behavior or
      potentiate masculinization processes of males. On the contrary, we observed a
      potentiation of female behavior in females and a depotentiation of male behavior
      in males.

PMID- 12060838
TI  - Exposure to a low dose of bisphenol A during fetal life or in adulthood alters
      maternal behavior in mice.
AB  - Maternal behavior in mammals is the result of a complex interaction between the
      lactating dam and her developing offspring. Slight perturbations of any of the
      components of the mother-infant interaction may result in alterations of the
      behavior of the mother and/or of the offspring. We studied the effects of
      exposure of female CD-1 mice to the estrogenic chemical bisphenol A (BPA) during
      fetal life and/or in adulthood during the last part of pregnancy on subsequent
      maternal behavior. Pregnant females were fed daily doses of corn oil (controls)
      or 10 microg/kg body weight BPA during gestation days 14-18. As adults, the
      prenatally treated female offspring were time-mated and again fed either corn oil
      (controls) or the same doses of BPA on gestation days 14-18, resulting in four
      treatment groups: controls, prenatal BPA exposure, adult BPA exposure, and both
      prenatal and adult BPA exposure. Maternal behavior was then observed on postnatal
      days 2-15 and reflex responses were examined in the offspring. Dams exposed to
      BPA either as fetuses or in adulthood spent less time nursing their pups and more
      time out of the nest compared with the control group. Females exposed to BPA both
      as fetuses and in adulthood did not significantly differ from controls. No
      alterations in postnatal reflex development were observed in the offspring of the
      females exposed to BPA. The changes seen in maternal behavior may be the result
      of a direct effect of BPA on the neuroendocrine substrates underlying the
      initiation of maternal behavior.

PMID- 12060839
TI  - The parvocellular vasotocin system of Japanese quail: a developmental and adult
      model for the study of influences of gonadal hormones on sexually differentiated
      and behaviorally relevant neural circuits.
AB  - Vasotocin (VT; the antidiuretic hormone of birds) is synthesized by diencephalic
      magnocellular neurons projecting to the neurohypophysis. A sexually dimorphic
      system of VT-immunoreactive (ir) parvocellular elements has been described within
      the male medial preoptic nucleus (POM) and the nucleus of the stria terminalis,
      pars medialis (BSTm). VT-ir fibers are present in many diencephalic and
      extradiencephalic locations, and quantitative morphometric analyses demonstrated
      their sexually dimorphic distribution in regions involved in the control of
      different aspects of reproduction. Moreover, systemic or intracerebroventricular
      injections of VT markedly inhibit the expression of some aspects of male sexual
      behavior. In adult animals, circulating levels of testosterone (T) have a
      profound influence on the VT immunoreactivity within BSTm, POM, and lateral
      septum. Castration markedly decreases the immunoreaction, whereas T-replacement
      therapy restores a situation similar to the intact birds. We observed no changes
      in gonadectomized females treated with T. These changes parallel similar changes
      in male copulatory behavior (not present in castrated male quail, fully expressed
      in castrated, T-treated males). The restoration by T of the VT immunoreactivity
      in castrated male quail could be fully mimicked by a treatment with estradiol
      (E(2)), suggesting that the aromatization of T into E(2) may play a key limiting
      role in both the activation of male sexual behavior and the induction of VT
      synthesis. This dimorphism has an organizational nature: administration of E(2)
      to quail embryos (a treatment that abolishes male sexual behavior) results in a
      dramatic decrease of the VT immunoreactivity in sexually dimorphic regions.
      Conversely, the inhibition of E(2) synthesis during embryonic life (a treatment
      that stimulates the expression of male copulatory behavior in treated females
      exposed in adulthood to T) results in a malelike distribution of VT
      immunoreactivity. The VT parvocellular system of the Japanese quail can therefore
      be considered an accurate marker of the sexual differentiation of brain circuits
      mediating copulatory behavior and could be a very sensitive indicator of the
      activity of estrogenlike substances on neural circuits.

PMID- 12060840
TI  - Aromatase activity in the ovary and brain of the eastern mosquitofish (Gambusia
      holbrooki) exposed to paper mill effluent.
AB  - Studies have shown that female mosquitofish living downstream of a paper mill
      located on the Fenholloway River, Florida, have masculinized secondary sex
      characteristics, including altered anal fin development and reproductive
      behavior. Masculinization can be caused by exposure to androgens in the water or
      from an alteration in aromatase activity in the fish. We hypothesized that
      aromatase activity would be inhibited by a component(s) of the paper mill
      effluent. Aromatase inhibition could masculinize the hormonal profile and,
      subsequently, secondary sex characteristics of the exposed females. Therefore, we
      predicted that ovarian and brain aromatase activity would be lower in the female
      mosquitofish from the Fenholloway River compared with the reference site, the
      Econfina River. Adult females were collected and standard length, body mass, anal
      fin length, and segment number were measured. Ovarian and brain aromatase
      activity were determined using a tritiated water assay. Fenholloway females had
      masculinized anal fin development as indicated by an increase in the number of
      segments in the longest anal fin ray (p < 0.0001), yet the length of the ray did
      not differ between sites (p = 0.95). Fenholloway females exhibited higher ovarian
      (p = 0.0039) and brain (p = 0.0003) aromatase activity compared with reference
      site fish. These data do not support aromatase inhibition as the mechanism for
      masculinization, suggesting that the masculinization of the Fenholloway female
      mosquitofish is due to androgenic contaminants. Future studies should examine the
      relationship between aromatase enzyme activity and exposure to environmental
      androgens.

PMID- 12060841
TI  - Androgens and environmental antiandrogens affect reproductive development and
      play behavior in the Sprague-Dawley rat.
AB  - In mammals, exposure to androgens early in development is essential for
      masculinization of the male reproductive phenotype. Male fetuses exposed to
      antiandrogens during perinatal life are permanently demasculinized in their
      morphology and physiology, whereas exposure to exogenous androgens permanently
      masculinizes females. In some litter-bearing species, proximity(italic) in
      utero(/italic) of females to males can partially masculinize female siblings and
      alter their responsiveness to endocrine-disrupting compounds. However, in our
      strain of rat (CD-SD Charles River), intrauterine position does not significantly
      influence testosterone concentrations and anogenital distance of fetuses. In
      comparison, administration of testosterone propionate to pregnant females, at
      doses that doubled fetal female testosterone levels, did masculinize the
      reproductive system. Discovery of androgen-active chemicals in the environment
      has placed increased emphasis on describing the reproductive and behavioral
      effects of both natural and environmental androgens and antiandrogens. Recently,
      the effects of an antiandrogen, vinclozolin, on the brain and behavior were cited
      as a special concern by the U.S. Environmental Protection Agency in its risk
      assessment of this pesticide. In rats, one such behavior that is perinatally
      organized by androgens is social play. Males play more than females, and
      administration of exogenous androgens during the neonatal period alters the
      juvenile expression of this sexually dimorphic behavior. Vinclozolin is an
      androgen receptor antagonist that inhibits androgen-dependent tissue growth in
      vivo. We were interested in whether developmental exposure to vinclozolin could
      also alter androgen-dependent behaviors such as play. Neonatal male rats were
      injected on postnatal days (PNDs) 2 and 3 with corn oil, the pharmacologic
      antiandrogen flutamide (50 mg/kg), or vinclozolin (200 mg/kg). On PNDs 36-37
      animals were observed for social play. Behaviors associated with general social
      activity such as sniffing and dorsal contact were unaffected by treatment.
      However, play behavior in males treated with flutamide or vinclozolin was
      significantly reduced, resembling levels of play characteristic of females rather
      than untreated males. Therefore, this study demonstrates that perinatal exposure
      to vinclozolin, an environmental antiandrogen, can alter androgen-dependent play
      behavior in the male rat.

PMID- 12060842
TI  - Birth defects, season of conception, and sex of children born to pesticide
      applicators living in the Red River Valley of Minnesota, USA.
AB  - We previously demonstrated that the frequency of birth defects among children of
      residents of the Red River Valley (RRV), Minnesota, USA, was significantly higher
      than in other major agricultural regions of the state during the years 1989-1991,
      with children born to male pesticide applicators having the highest risk. The
      present, smaller cross-sectional study of 695 families and 1,532 children,
      conducted during 1997-1998, provides a more detailed examination of reproductive
      health outcomes in farm families ascertained from parent-reported birth defects.
      In the present study, in the first year of life, the birth defect rate was 31.3
      births per 1,000, with 83% of the total reported birth defects confirmed by
      medical records. Inclusion of children identified with birth or developmental
      disorders within the first 3 years of life and later led to a rate of 47.0 per
      1,000 (72 children from 1,532 live births). Conceptions in spring resulted in
      significantly more children with birth defects than found in any other season
      (7.6 vs. 3.7%). Twelve families had more than one child with a birth defect (n =
      28 children). Forty-two percent of the children from families with recurrent
      birth defects were conceived in spring, a significantly higher rate than that for
      any other season. Three families in the kinships defined contributed a first
      degree relative other than a sibling with the same or similar birth defect,
      consistent with a Mendelian inheritance pattern. The remaining nine families did
      not follow a Mendelian inheritance pattern. The sex ratio of children with birth
      defects born to applicator families shows a male predominance (1.75 to 1) across
      specific pesticide class use and exposure categories exclusive of fungicides. In
      the fungicide exposure category, normal female births significantly exceed male
      births (1.25 to 1). Similarly, the proportion of male to female children with
      birth defects is significantly lower (0.57 to 1; p = 0.02). Adverse neurologic
      and neurobehavioral developmental effects clustered among the children born to
      applicators of the fumigant phosphine (odds ratio [OR] = 2.48; confidence
      interval [CI], 1.2-5.1). Use of the herbicide glyphosate yielded an OR of 3.6
      (CI, 1.3-9.6) in the neurobehavioral category. Finally, these studies point out
      that (a) herbicides applied in the spring may be a factor in the birth defects
      observed and (b) fungicides can be a significant factor in the determination of
      sex of the children of the families of the RRV. Thus, two distinct classes of
      pesticides seem to have adverse effects on different reproductive outcomes.
      Biologically based confirmatory studies are needed.

PMID- 12060844
TI  - G-CSF: function and modes of action (Review).
AB  - Since the observations in the 1960s that granulocyte-colony stimulating factor (G
      CSF) stimulated the proliferation of granulocytic cells in semisolid cultures of
      bone marrow cells, G-CSF has established itself as a useful clinical agent for
      increasing levels of neutrophilic granulocytes. However, these early findings did
      not firmly establish whether G-CSF is a genuine regulator of granulocyte
      formation under normal physiological conditions or rather acts as an emergency
      regulator, playing an important role only under stress conditions. The advent of
      <gene-knockout technology> has allowed us to evaluate these questions in a
      physiological setting through analysis of mice with a targeted mutation of G-CSF
      or its receptor, while the development of relevant cell models has enabled us to
      dissect the molecular basis of G-CSF action. This review discusses our current
      state of knowledge regarding the role of G-CSF in granulopoiesis.

PMID- 12060845
TI  - Strabismus (STB)/Vang-like (VANGL) gene family (Review).
AB  - Strabismus 1 (STB1/VANGL2) and Strabismus 2 (STB2/VANGL1), which have been cloned
      and characterized using bioinformatics and cDNA-PCR, are human homologues of
      Drosophila tissue polarity gene strabismus (stbm)/Van Gogh (Vang). STB1 and STB2
      are tetra-membrane-spanning proteins with 73.1% total-amino-acid identity. Serine
      rich domain and Strabismus-homology (STH1 and STH2) domains are conserved among
      human STB1, STB2, Xenopus Stbm, and Drosophila Stbm. STH2 domain with the C
      terminal Ser/Thr-X-Val motif is implicated in binding with Dishevelled (DVL)
      proteins. STB1 gene is clustered with CASQ1 gene on human chromosome 1q21-q23,
      while STB2 gene is clustered with CASQ2 gene on human chromosome 1p13. STB1 and
      STB2 genes are located around cancer susceptibility loci or recombination hot
      spots in the human genome. STB1 is moderately expressed in K-562 (leukemia), G
      361 (melanoma), and MKN7 (gastric cancer) cells. STB2 is highly expressed in
      MKN28, MKN74 (gastric cancer), BxPC-3, PSN-1, and Hs766T (pancreatic cancer)
      cells. On the other hand, STB1 and STB2 are significantly down-regulated in
      several cancer cell lines and primary tumors. Xenopus homologue of human STB1 and
      STB2 regulates negatively the WNT - beta-catenin signaling pathway. Loss-of
      function mutations of genes encoding negative regulators of WNT - beta-catenin
      signaling pathway lead to carcinogenesis. Based on functional aspects and human
      chromosomal loci, STB1 gene and STB2 gene are predicted to be potent tumor
      suppressor gene candidates. STB1 and STB2 might be suitable targets for tissue
      engineering in the field of re-generative medicine and for chemoprevention and
      treatment in the field of clinical oncology.

PMID- 12060846
TI  - Localization and regulation of bovine eye calmodulin-dependent cyclic nucleotide
      phosphodiesterase by cyclic AMP-dependent protein kinase.
AB  - Calmodulin-dependent cyclic nucleotide phosphodiesterase is one of the key
      enzymes involved in the complex interactions, which occur between the cyclic
      nucleotide and Ca2+ second-messenger systems. In eye, cAMP regulation is
      important in a variety of physiological processes such as aqueous humor
      regulation, photoreceptor signal transduction and retinal blood flow. Bovine eye
      calmodulin-dependent cyclic nucleotide phosphodiesterase was purified to apparent
      homogeneity and the isolated enzyme had a significantly higher affinity for
      calmodulin and Ca2+. Immunohistology revealed calmodulin-dependent cyclic
      nucleotide phospho-diesterase expression in corneal epithelium, retina and optic
      nerve of the eye. The cAMP-dependent protein kinase was found to catalyze the
      phosphorylation of bovine eye calmodulin-dependent cyclic nucleotide
      phosphodiesterase and the following observations were made. Firstly, the
      phosphorylation resulted in the incorporation of 1 mol of phosphate per mol of
      subunit, resulting in higher calmodulin and Ca2+ concentration requirement for
      calmodulin-dependent cyclic nucleotide phosphodiesterase activation. Secondly,
      Ca2+ and calmodulin prevented the phosphorylation. Thirdly, the phosphorylation
      of calmodulin-dependent cyclic nucleotide phosphodiesterase could be reversed by
      the calmodulin-dependent phosphatase, calcineurin. Analysis of the complex
      regulatory properties of the calmodulin-dependent cyclic nucleotide
      phosphodiesterase in the eye has led to the suggestion that fluxes of cAMP and
      Ca2+ during cell activation are closely coupled and that calmodulin-dependent
      cyclic nucleotide phosphodiesterase plays a key role in this signal coupling
      phenomenon.

PMID- 12060847
TI  - Interactions between human monocytes and fibronectin are suppressed by
      interferons beta and gamma, but not alpha: correlation with Rho-paxillin
      signaling.
AB  - Modulation of the adhesive responses of monocytic cells may reflect their
      motility at sites of diseased tissues (inflammation, tumors). Integrins
      alpha5beta1 mediate fibronectin (Fn)-dependent adhesion of human monocytes and
      their precursors. The effect of type I IFNs (alpha, beta) and type II IFN (gamma)
      was assessed on the adhesive capacities of promonocytic U937 cells and monocytes.
      IFN-beta and IFN-gamma abrogated monocytic cell adhesion to Fn, but such impaired
      cell attachment was not due to altered levels of alpha5beta1 integrins. In
      contrast, IFN-alpha did not affect cell adhesion to Fn. Participation of
      cytoskeleton assembly in IFN-mediated cell detachment was evaluated. Activation
      of RhoA activity with lysophosphatidic acid (LPA) increased 2-fold the adhesion
      of monocytic cells to Fn in a alpha5beta1-mediated fashion, and IFN-gamma
      treatment reversed the enhancing effect of LPA. Moreover, U937 cells and
      monocytes dominantly expressed the 44-46 kDa paxillin forms and IFN-beta and IFN
      gamma led to the accumulation of 66-70 kDa paxillin forms. These results indicate
      that IFN-mediated loss of monocyte adhesion to Fn is associated with changes in
      the cytoskeleton associated proteins paxillin and Rho.

PMID- 12060848
TI  - Age independent expression of myocilin in the human trabecular meshwork.
AB  - Glaucoma is a leading cause of blindness. Primary open-angle glaucoma, the most
      common form of glaucoma, is known to increase in prevalence with age. One of its
      major risk factors is an elevated intraocular pressure believed to be related to
      the trabecular meshwork (TM), a specialized tissue located at the chamber angle
      of the eye. Myocilin, a gene linked to open-angle glaucomas (OAG), has been found
      to be expressed in the TM and a broad range of other ocular and non-ocular
      tissues. The purpose of this study was to examine the distribution of myocilin
      protein and mRNA in the TM of normal human eyes to determine whether age-related
      changes exist. Studies with glaucomatous eyes were carried out concurrently.
      Immunoperoxidase staining experiments demonstrated positive immunoreactivity for
      myocilin protein in both the cells and beams in all regions of the TM. The
      staining intensity and the myocilin level as determined by dot blot assays were
      not correlated with the ages of donors ranging from 8 weeks to 93 years. Neither
      did myocilin mRNA, detected by in situ hybridization in cells throughout the TM
      and quantified by relative quantitative RT-PCR, vary with age. Myocilin mRNA and
      protein expression in diseased tissues was either comparable to that of normal
      tissues or reduced. This study represents the first in-depth investigation of
      myocilin expression in relation to age in the TM of human eyes. The results
      indicate an age independence, argue thus against a direct role of myocilin and
      reiterate the involvement of additional factors in the pathogenesis of glaucoma.

PMID- 12060849
TI  - Expression of HOXD9 in fibroblast-like synoviocytes from rheumatoid arthritis
      patients.
AB  - The proteins of homeobox (HOX) genes are transcription regulators involved in
      cell type-specific differentiation and patterning of the body plan in
      vertebrates. Particularly, the HOXD family is involved in limb formation in mice
      and chicks. There is also some evidence that the HOXD9 gene, a member of the HOXD
      family, is involved in the pathology of rheumatoid arthritis (RA). The purpose of
      the present study was to determine if the HOXD9 protein was expressed in RA
      synovium and then to characterize the HOXD9-expressing cell. Western blotting and
      immunohistochemical analysis showed that the HOXD9 protein was expressed in the
      synovium from patients with RA, but not in those from patients with
      osteoarthritis or healthy individuals. The HOXD9-positive cells were localized in
      both the lining and sublining areas of the synovium. Furthermore, fluorescent
      double-staining showed that the HOXD9 protein was expressed in fibroblast-like
      synoviocytes (FLS). These findings not only indicate that the HOXD9 gene is
      exclusively expressed in the RA synovium but also suggest that the HOXD9 gene
      contributes to the pathology of rheumatoid arthritis through the FLS.

PMID- 12060843
TI  - Cancer risk assessment, indicators, and guidelines for polycyclic aromatic
      hydrocarbons in the ambient air.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion.
      Domestic wood burning and road traffic are the major sources of PAHs in Sweden.
      In Stockholm, the sum of 14 different PAHs is 100-200 ng/m(3) at the street-level
      site, the most abundant being phenanthrene. Benzo[a]pyrene (B[a]P) varies between
      1 and 2 ng/m(3). Exposure to PAH-containing substances increases the risk of
      cancer in humans. The carcinogenicity of PAHs is associated with the complexity
      of the molecule, i.e., increasing number of benzenoid rings, and with metabolic
      activation to reactive diol epoxide intermediates and their subsequent covalent
      binding to critical targets in DNA. B[a]P is the main indicator of carcinogenic
      PAHs. Fluoranthene is an important volatile PAH because it occurs at high
      concentrations in ambient air and because it is an experimental carcinogen in
      certain test systems. Thus, fluoranthene is suggested as a complementary
      indicator to B[a]P. The most carcinogenic PAH identified, dibenzo[a,l]pyrene, is
      also suggested as an indicator, although it occurs at very low concentrations.
      Quantitative cancer risk estimates of PAHs as air pollutants are very uncertain
      because of the lack of useful, good-quality data. According to the World Health
      Organization Air Quality Guidelines for Europe, the unit risk is 9 X 10(-5) per
      ng/m(3) of B[a]P as indicator of the total PAH content, namely, lifetime exposure
      to 0.1 ng/m(3) would theoretically lead to one extra cancer case in 100,000
      exposed individuals. This concentration of 0.1 ng/m(3) of B[a]P is suggested as a
      health-based guideline. Because the carcinogenic potency of fluoranthene has been
      estimated to be approximately 20 times less than that of B[a]P, a tentative
      guideline value of 2 ng/m(3) is suggested for fluoranthene. Other significant
      PAHs are phenanthrene, methylated phenanthrenes/anthracenes and pyrene (high air
      concentrations), and large-molecule PAHs such as dibenz[a,h]anthracene,
      benzo[b]fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene (high
      carcinogenicity). Additional source-specific indicators are benzo[ghi]perylene
      for gasoline vehicles, retene for wood combustion, and dibenzothiophene and
      benzonaphthothiophene for sulfur-containing fuels.

PMID- 12060850
TI  - Bovine enterovirus as an oncolytic virus: foetal calf serum facilitates its
      infection of human cells.
AB  - Many viruses have been investigated for their oncolytic properties and potential
      use as therapeutic agents for cancer treatment. Most of these replication
      competent viruses are human pathogens. We investigated the oncolytic properties
      of an animal virus which is non pathogenic for both its natural host and humans.
      Bovine enterovirus has previously been shown to exhibit a very wide tissue
      tropism for cell types in vitro. We compare the ability of bovine enterovirus to
      replicate in and to cause cytopathic effect in freshly isolated human monocytes
      and monocyte derived macrophages with the monocyte-like U937 tumour cell line. We
      also include the adherent ZR-75-1 human breast cancer cell line. We have also
      carried out infections of bovine enterovirus in the presence and in the absence
      of serum of bovine origin. Our study shows that the virus will replicate in and
      produce cytopathic effect in the U937 and ZR-75-1 cell types to the same extent
      as the cells (BHK-21) in which the virus is routinely propagated. We believe
      bovine enterovirus to be a worthwhile candidate for further study as an anti
      tumour agent.

PMID- 12060851
TI  - Allelic imbalance in hMLH1 or BRCA2 loci associated with response of cervical and
      endometrial cancer to radiotherapy.
AB  - Effectiveness of radiotherapy is influenced by several genetic properties of the
      targeted cells. The aim of this study was the identification of prognostic
      indicators of tumor response to radiation in cervical and endometrial cancer.
      Using microsatellite DNA analysis, we investigated 31 markers, located on 1p, 2p,
      2q, 3p, 9p, 9q, 13q, 17p and 17q for genomic alterations in 37 cervical and 21
      endometrial cancer cases, with complete follow-up data. Genetic alterations of
      the initial tumor genotypes were observed after radiation in 86.5% of cervical
      and 81.0% of endometrial cases. Reversions to the original normal genotype were
      observed in 40.5 and 28.6% respectively, predominantly in cured patients rather
      than in recurred cases. Survival curves by the Kaplan-Meier method showed a worse
      prognosis for cervical cancer patients whose tumors harbor allelic imbalance (AI)
      on 3p or 13q, and for endometrial cancer patients whose tumors harbor AI on 13q.
      Our data suggest a possible association of the hMLH1 or BRCA2 genes, implicated
      in distinct DNA repair pathways and located on 3p and 13q respectively, with
      response of cervical and endometrial cancer to radiotherapy. Moreover,
      microsatellite DNA analysis before and after radiation treatment could be used as
      a marker of the clinical outcome of patients.

PMID- 12060852
TI  - Activation and repression of growth factor receptor gene transcription (Review).
AB  - Growth factor receptors mediate cell signaling events that regulate a diverse
      array of cellular activities including cell proliferation, homeostasis, and
      differentiation of both normal and cancer cells. Studies of the mechanisms
      governing transcription of growth factor receptor genes have revealed common
      structural features of their promoters. These common features include GC rich
      promoter regions and multiple Sp factor binding sites based upon which most of
      these promoters are transactivated. Mechanisms of growth factor receptor promoter
      activation via these common structural features will be reviewed, with particular
      attention to control of FGFR1 promoter activity in skeletal muscle cells. Of
      equal importance in cellular function is the repression of growth factor receptor
      signaling and gene expression. Mechanisms that repress growth factor receptor
      promoter activity operate via direct repression at transcriptional activator
      binding sites and via protein-protein interactions that abrogate activator
      function. Mechanisms of growth factor receptor transcriptional repression will be
      considered in the context of known tumor suppressors, transcription activator
      availability, as well as in light of emerging potential Sp1-like transcriptional
      repressors.

PMID- 12060853
TI  - Endogenous expression of interleukin-8 and interleukin-10 in nasopharyngeal
      carcinoma cells and the effect of photodynamic therapy.
AB  - Interleukin-8 (Il-8) and IL-10 are cytokines associated with the Epstein Barr
      Virus (EBV), which is linked with nasopharyngeal cancer (NPC). In the present
      study, we investigated the endogenous production of IL-8 and IL-10 in vitro by
      two EBV-positive NPC cell lines, viz., HK1 and CNE-2. IL-8 was expressed by both
      cell lines although the level of IL-8 was 2-fold higher in supernatant from HK1
      cells. Incubation with hypericin, a natural photosensitizer increased IL-8
      significantly but only in HK1 cells. Hypericin-based photodynamic therapy (PDT)
      did not alter the expression of IL-8 levels. Il-10 was not constitutively
      expressed in either cell line and could not be induced by PDT. It is interesting
      that PDT which is known to upregulate IL-8 transcription via reactive oxygen
      species and activate the IL-10 promoter did not alter IL-8 levels in either of
      the NPC cell lines nor induced the production of IL-10.

PMID- 12060854
TI  - Noradrenergic and cholinergic innervation of the bone marrow.
AB  - Bone marrow is supplied by sensory and autonomic innervation. Although it is well
      established that hematopoiesis is regulated by cytokines and cell-to-cell
      contacts, the role played by neuromediators on the proliferation, differentiation
      and release of hematopoietic cells is still controversial. We studied the
      innervation of rat femur bone marrow by means of fluorescence histochemistry and
      immunohistochemistry. Glyoxylic acid-induced fluorescence was used to demonstrate
      catecholaminergic nerve fibers. The immunoperoxidase method with nickel
      amplification was applied to detect the distribution of nerve fibers using
      antibodies against the general neuronal marker PGP 9.5 (neuron-specific
      cytoplasmic protein), while the cholinacetyltransferase immunoreactivity was
      studied by immunohistochemistry. Our results show the presence of an extensive
      network of innervation in the rat bone marrow, providing a morphological basis
      for the neural modulation of hemopoiesis.

PMID- 12060855
TI  - Investigation of the effect of different regulatory peptides on adrenocortical
      cell proliferation in immature rats: evidence that endogenous adrenomedullin
      exerts a stimulating action.
AB  - Compelling evidence indicates that the active growth of immature rat adrenal
      glands is sustained not only by an increased release of pituitary ACTH, but also
      by other ancillary mechanisms. We investigated whether vasoactive intestinal
      peptide (VIP), atrial natriuretic peptide (ANP), adrenomedullin (ADM) and
      proadrenomedullin N-terminal 20 peptide (PAMP) play a relevant role in these
      mechanisms. These four regulatory peptides were chosen because previous studies
      demonstrated that they are expressed in rat adrenals and are able to modulate the
      secretory activity and growth of zona glomerulosa (ZG), i.e., the adrenal layer.
      Groups of immature (20-day old) rats were given three subcutaneous injections
      (28, 16 and 4 h before sacrifice) of 2 nmol/100 g of the four peptides and/or
      selective antagonists of their receptors (VIP-A, ANP-A, ADM-A and PAMP-A), and
      0.1 mg/100 g vincristin 3 h before autopsy. Adrenal glands were collected,
      processed for light microscopy, and the mitotic index (MI; percentage of
      metaphase-arrested cells) was evaluated in the subcapsular ZG. Neither VIP nor
      VIP-A affected MI. Both ANP and ANP-A decreased MI and their effects displayed
      additivity. ADM and PAMP raised MI and the effect was abolished by ADM-A and PAMP
      A, respectively. When administered alone ADM-A, but not PAMP-A, significantly
      lowered MI. Collectively, our findings suggest that: i) neither VIP nor PAMP are
      involved in the regulation of immature rat adrenals; ii) ANP exerts a non
      receptor-mediated inhibitory action, whose physiological relevance remains to be
      investigated; and iii) endogenous ADM system plays a relevant role in the
      mechanisms underlying the maintenance of high growth rate during adrenal
      maturation.

PMID- 12060856
TI  - Adrenomedullin and its receptors are expressed in the zona glomerulosa of
      immature and adult rat adrenals: evidences of upregulation of ADM system in
      immature glands.
AB  - Evidence has been provided that adrenomedullin (ADM) stimulates the proliferative
      activity of adult rat adrenal zona glomerulosa (ZG). However, the selective ADM
      receptor antagonist ADM(22-52), although being able to block ADM effect, was per
      se ineffective. In contrast, in the companion paper, we showed that ADM(22-52)
      depresses the proliferation rate of ZG in 20-day-old rats, suggesting the
      involvement of endogenous ADM system in adrenal maturation. Hence, we
      investigated by semiquantitative reverse transcription-polymerase chain reaction
      and radioimmune assay the expression of ADM system in adult and immature rat ZG.
      ProADM mRNA and ADM-immunoreactivity were both more elevated in immature- than
      adult-rat ZG. Plasma ADM concentration did not show significant age-related
      differences. ADM acts via two subtypes of ADM(22-52)-sensitive receptors: the L1
      receptor (L1-R) and the calcitonin-receptor-like-receptor (CRLR), the latter
      behaves as selective ADM receptor only in the presence of the receptor-activity
      modifying proteins (RAMPs)2 and 3. L1-R expression was enhanced in immature rat
      ZG, while CRLR and RAMP(2,3) expression did not display significant differences.
      It is concluded that the endogenous ADM system located in the ZG is upregulated
      in immature rats, and plays an important autocrine-paracrine role in the
      maintenance of the elevated growth rate during adrenal maturation.

PMID- 12060857
TI  - Inhibitory effects of somatostatin on tumor necrosis factor-alpha-induced
      interleukin-6 secretion in human pancreatic periacinar myofibroblasts.
AB  - Pancreatic periacinar myofibroblasts are considered to be therapeutic targets for
      the suppression of acute pancreatitis. To elucidate the mechanisms mediating the
      therapeutic actions of somatostatin on acute pancreatitis, we investigated how
      somatostatin affects the tumor necrosis factor (TNF)-alpha-induced interleukin
      (IL)-6 and IL-8 secretion from pancreatic myofibroblasts. Cytokine secretion was
      determined by enzyme-linked immunosorbent assay (ELISA) and Northern blotting.
      Nuclear factor (NF)-kappaB DNA-binding activity was evaluated by electrophoretic
      mobility shift assay (EMSAs). The expression of somatostatin receptor (SSTR) mRNA
      was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).
      Somatostatin dose-dependently inhibited the TNF-alpha-induced IL-6 secretion. In
      comparison, the effects on IL-8 secretion were modest. Northern blot analysis
      demonstrated that somatostatin decreased the TNF-alpha-induced IL-6 mRNA
      expression, and that this effect was completely blocked by the somatostatin
      antagonist cyclo-somatostatin. Furthermore, somatostatin suppressed TNF-alpha
      induced NF-kappaB activation. These cells bear SSTR subtypes 1 and 2.
      Somatostatin down-regulated the TNF-alpha-induced IL-6 secretion in human
      pancreatic periacinar myofibroblasts. These findings suggest that some of the
      therapeutic actions of somatostatin on acute pancreatitis might be mediated by
      reducing local IL-6 secretion in the pancreas.

PMID- 12060858
TI  - Expression of BLM (the causative gene for Bloom syndrome) and screening of Bloom
      syndrome.
AB  - Bloom syndrome (BS) is a rare autosomal recessive genetic disorder characterized
      by growth deficiency, unusual facies, sun-sensitive telangiectatic erythema,
      immunodeficiency and predisposition to cancer. The causative gene for BS is the
      BLM gene which encodes the BLM RecQ helicase protein. The BLM gene has 4437 bp
      and encodes 1417 amino acids. The detection of BLM gene mutations for laboratory
      diagnosis of BS is laborious and impractical, unless there are common mutations
      in a population. Here we describe the immunoblot and immunohistochemical analyses
      for the detection of the BLM protein using a polyclonal BLM antibody. The BLM
      gene and protein were consistently and clearly detected in Epstein-Barr virus
      (EBV)-transformed or phytohemagglutinin (PHA)-stimulated lymphoblasts from
      control and various human hematopoietic cell lines. In a 7-week old human fetal
      brain, the BLM gene expression was strongly detected in contrast to an adult
      human brain. The BLM protein was not detected in EBV-transformed lymphoblasts
      from three BS patients. By immunohistochemistry, nuclear dots of the BLM protein
      were detected in both EBV-transformed lymphoblasts and PHA-stimulated
      lymphoblasts from the control. However, in lymphoblasts from BS patients no
      nuclear dots of the BLM protein were detected. These results indicate that the
      combinational analysis of immunoblotting and immunohistochemistry is a useful
      approach to screening of BS, although a mutation analysis is necessary for a
      definitive diagnosis of BS.

PMID- 12060859
TI  - HOX11L1: a promoter study to evaluate possible expression defects in intestinal
      motility disorders.
AB  - Intestinal Neuronal Dysplasia (IND) is a congenital disorder characterized by
      intestinal motility defects associated with hyperplasia of enteric ganglia. A
      phenotype resembling human IND has been observed in mice knocked-out for a member
      of the Hox11 homeobox gene family, Hox11l1, suggesting that the human homologue
      of this gene could be responsible for congenital disorders of intestinal
      innervation. However, previous mutation analysis of the coding sequence of the
      HOX11L1 gene in patients affected with IND detected neither mutations nor other
      nucleotide variants. In the present work, a detailed study of the non coding
      promoter region of this gene was undertaken in patients affected with IND, with
      Hirschsprung associated IND and with neurogenic chronic intestinal pseudo
      obstruction. No alterations potentially impairing expression of HOX11L1, such as
      nucleotide variants, small deletions or cytogenetic alterations, could be
      identified thus further excluding the direct involvement of this gene in the
      pathogenesis of human intestinal motility disorders.

PMID- 12060860
TI  - Enhancing and suppressing effects of dexamethasone on transgene expression in
      vitro.
AB  - Gene therapy is becoming an important treatment modality against various diseases
      including cancer, genetic disorders, infectious diseases and inflammatory
      diseases. For achieving successful gene therapy, it is extremely important to
      control the expression of a transduced therapeutic gene. However, there have been
      few studies examining the effect of glucocorticoid on transgene expression. We
      demonstrate here that the synthetic glucocorticoid dexamethasone significantly
      affected transgene expression in vitro. Bone marrow cells freshly prepared from
      rats and murine fibroblasts were infected with retroviruses carrying the neomycin
      phosphotransferase gene under the transcriptional control of the retroviral long
      terminal repeat promoter and the reporter lacZ gene under the transcriptional
      control of the simian virus 40 (SV40) early promoter. Retrovirus-infected cells
      were selected by G418. When retrovirus-infected bone marrow cells were cultured
      in the presence of dexamethasone, lacZ expression was markedly decreased. This
      suppressive effect of dexamethasone on transgene expression in bone marrow cells
      appeared to be mediated by a methylation-independent mechanism, because the
      suppressive effect was also observed in bone marrow cells that were supposed to
      contain a considerable number of methylated cells. In marked contrast, when
      retrovirus-infected fibroblasts were cultured in the presence of dexamethasone,
      lacZ expression was significantly increased. The enhancing and suppressing
      effects of dexamethasone on transgene expression were considered to be
      independent on promoter types, because the SV40 early promoter used to control
      lacZ expression does not contain a glucocorticoid-responsive element. Therefore,
      the different effects of dexamethasone on transgene expression appeared to be
      dependent on cell types. These results indicate that dexamethasone may play an
      important role for achieving successful gene therapy. Furthermore, these
      observations may also have important implications for future clinical
      applications of gene therapy.

PMID- 12060861
TI  - Polymerase chain reaction-based clonality analysis in thyroid lymphoma.
AB  - A previous patho-epidemiological study indicated that thyroid lymphoma (TL)
      evolves among active lymphoid cells into chronic lymphocytic thyroiditis (CLTH),
      a thyroid-specific autoimmune disease. In this study, clonality of B-cells in the
      CLTH and TL lesions was analyzed using polymerase chain reaction (PCR)-based
      method on surgically resected samples from 10 cases of TL; 7 mucosa-associated
      lymphoid tissue (MALT) lymphoma and 3 diffuse large B-cell lymphoma (DLBCL). CLTH
      lesions coexisted in all the cases with MALT lymphoma, but not in the three DLBCL
      cases. In cases of MALT lymphoma, the lymphomatous and CLTH areas were separately
      microdissected from each section and analyzed for clonality. In the cases of
      DLBCL, the whole specimens were used for clonality analysis. CLTH lesions showed
      smear in 6 samples, two bands in one, and more than three (oligoclonal pattern)
      in 2. MALT lymphoma lesions showed single or two bands (monoclonal pattern) in 4,
      oligoclonal pattern in 4, and smear in one. DLBCL showed monoclonal pattern in
      two and oligoclonal pattern in one. One common band was present among two
      separate MALT lesions in one case, but no common bands were found in the
      remaining six cases. These findings suggested the clonal evolution of B-cell from
      polyclonal to monoclonal proliferation to take place in the continuum of
      lymphoproliferative lesions into autoimmune thyroiditis.

PMID- 12060862
TI  - Molecular cloning and characterization of mouse St7r (St7-like, St7l).
AB  - Human ST7R (ST7-like, ST7L) is a paralog of tumor suppressor gene ST7 in the
      human genome. ST7R gene is clustered with WNT2B gene in human chromosome 1p13,
      while ST7 gene is clustered with WNT2 gene in human chromosome 7q31. Here, we
      have cloned mouse ortholog of human ST7R using bioinformatics and cDNA-PCR. Mouse
      St7r was found to encode 559 amino-acid polypeptide. Mouse St7r showed 90.7%
      total-amino-acid identity with human ST7R isoform 4 (ST7R4), and 71.6% total
      amino-acid identity with human ST7 and mouse St7. Three tyrosine-phosphorylation
      sites as well as ST7R homologous domains (S7H1, S7H2, and S7H3) were conserved
      among mouse St7r, human ST7R, mouse St7, and human ST7. Leucine zipper domain of
      mouse St7r was conserved in human ST7R, but not in mouse St7 and human ST7. Mouse
      St7r was expressed almost ubiquitously in adult mouse tissues and also in mouse
      embryos. Although mouse genome draft sequence including mouse St7r gene has not
      yet been identified, rat genome draft sequence AC106372.1 was found to include
      rat St7r gene as well as rat Wnt2b gene. These results indicate evolutional
      conservation of ST7R-WNT2B gene cluster. This is the first report on molecular
      cloning and initial characterization of mouse St7r.

PMID- 12060863
TI  - Effectiveness of bioremediation of crude oil contaminated subantarctic intertidal
      sediment: the microbial response.
AB  - A field study was initiated in February 1996 in a remote sandy beach of The
      Grande Terre (Kerguelen Archipelago, 69 degrees 42 degrees E, 49 degrees 19
      degrees S) with the objective of determining the long-term effects of some
      bioremediation agents on the biodegradation rate and the toxicity of oil residues
      under severe subantarctic conditions. A series of 10 experimental plots were
      settled firmly into sediment. Each plot received 2L of Arabian light crude oil
      and some of them were treated with bioremediation agents: slow release fertilizer
      Inipol EAP-22 (Elf Atochem) or fish composts. Plots were sampled on a regular
      basis over a 3-year period. A two-order of magnitude increase of saprophytic and
      hydrocarbon-utilizing microorganisms occurred during the first month of the
      experiment in all treated enclosures, but no clear differences appeared between
      the plots. Very high microbial populations were present during the experiment.
      Biodegradation within treated spots was faster than within the untreated ones and
      appeared almost complete after 6 months as indicated by the degradation index of
      aliphatic hydrocarbons within all plots. The analysis of interstitial water
      collected below the oily residues presented no toxicity. However, a high toxicity
      signal, using Microtox solid phase, appeared for all oiled sand samples with a
      noticeable reduction with time even if the toxicity signal remained present and
      strong after 311 days of oil exposition. As a conclusion, it is clear that the
      microbial response was rapid and efficient in spite of the severe weather
      conditions, and the rate of degradation was improved in presence of
      bioremediation agents. However, the remaining residues had a relatively high
      toxicity.

PMID- 12060864
TI  - Diel patterns of UVBR-induced DNA damage in picoplankton size fractions from the
      Gulf of Aqaba, Red Sea.
AB  - This study focuses on the impact of natural levels of UVBR (ultraviolet-B
      radiation: 280 to 315 nm) on bacterio- and phytoplankton (<10 microm) from the
      Gulf of Aqaba, Red Sea. Incident biologically effective doses (BEDs) and
      attenuation of biologically effective radiation in the water column were measured
      using a DNA biodosimeter. UVBR-induced DNA damage was measured as cyclobutane
      pyrimidine dimers (CPDs), using an antibody directed to CPDs followed by
      chemiluminescent detection. Depth profiles of DNA damage were determined in two
      plankton size fractions (0.2 to 0.8 microm and 0.8 to 10 microm) collected down
      to 50 m depth. Furthermore, accumulation and removal of CPDs were monitored in
      surface plankton samples during several daily cycles. Small plankton (plankton
      <10 microm) composition was determined by flow cytometry. The plankton community
      in the Gulf of Aqaba was dominated by nonphototrophic bacteria and the free
      living prochlorophyte Prochlorococcus spp. (<0.8 microm). In general, no DNA
      damage could be detected in dosimeter DNA below 15 m. In contrast, DNA damage (up
      to 124 CPD Mnucl-1) could be detected in all bacterio- and phytoplankton samples.
      DNA damage accumulated throughout the day, indicating that plankton in the Gulf
      of Aqaba undergo UVBR stress via CPD induction. Although the numbers of CPDs
      decreased during darkness, both size fractions showed some residual DNA damage at
      the end of the night. This suggests that dark repair processes did not remove all
      CPDs, or that part of the plankton community was incapable of repair at all. CPD
      levels in the two size fractions showed no significant differences in situ.
      During full solar radiation exposures (samples incubated in bags), more CPDs were
      detected in the smaller (0.2 to 0.8 microm) size fraction as compared to the
      larger (0.8 to 10 microm) size fraction. In these experiments, initial plankton
      composition was significantly different from the field samples. This implies that
      a shift in the population structure or irradiance conditions can lead to a
      significant change in UVBR sensitivity. In conclusion, the results show that the
      picoplankton-dominated phyto- and bacterioplankton communities in the clear
      surface waters from the Gulf of Aqaba undergo UVBR stress. Repair pathways are
      not sufficient to eliminate damage during or after UVBR exposure hours,
      suggesting photomortality as a potential loss parameter of the plankton
      community.

PMID- 12060865
TI  - Bone mineral content and density in the humerus of adult myostatin-deficient
      mice.
AB  - Myostatin (GDF-8), a member of the transforming growth factor-b superfamily of
      secreted growth and differentiation factors, is a negative regulator of skeletal
      muscle growth. We investigated the effects of increased muscle mass on bone
      morphology by examining bone mineral content and density in the humeri of
      myostatin-deficient mice. We compared the humeri of 11 mixed-gender, adult mice
      homozygous for the disrupted myostatin sequence with those from 11 mixed-gender,
      adult wild-type mice. Body mass, deltoid mass, and triceps mass were recorded
      from each animal and densitometric and geometric parameters were collected from
      the humerus using peripheral quantitative computed tomography (pQCT). Cross
      sectional slices were scanned at four different positions along the humerus
      corresponding to 15%, 40%, 60%, and 85% of total humerus length. Results show
      that the myostatin- deficient mice weigh more than controls and have
      significantly larger triceps and deltoid muscles. The myostatin-deficient animals
      also have significantly (P < 0.05) higher trabecular area and trabecular bone
      mineral content (BMC) in the proximal humerus (15% length) and significantly (P <
      0.01) higher cortical BMC, cortical area, and periosteal circumference in the
      region of the deltoid crest (40% length). The myostatin knockouts otherwise do
      not differ from controls in cortical BMC. Moreover, experimental and control mice
      do not differ significantly from one another in cortical bone mineral density
      (BMD) at any of the sites examined. These results suggest that the effects of
      increased muscle mass on the mouse humerus are localized to regions where muscles
      attach; furthermore, these effects include increased mineral content of both
      trabecular and cortical bone.

PMID- 12060866
TI  - Comparison of inhibitory activity on calcium phosphate precipitation by acidic
      proline-rich proteins, statherin, and histatin-1.
AB  - This study quantitatively compares the inhibition of calcium phosphate (CaP)
      precipitation by the salivary acidic proline-rich proteins (PRPs) statherin and
      histatin-1. Saliva and CaCl2 in 125 mM imidazole buffer (pH 7.0) were incubated
      with potassium phosphate and a hydroxyapatite (HAP) suspension, for 30 min at 25
      degrees C, then filtered through nitrocellulose. The calcium (Ca) concentration
      in the filtrate was measured by atomic absorption spectrophotometry, then
      deducted from that in the initial solution to determine the amount of CaP
      precipitation after 30 min. The values of the inhibitory activities on CaP
      precipitation relative to crude parotid saliva were 4.7, 4.9, 6.9, and 65.8 for
      histatin-1, large PRPs, small PRPs, and statherin, respectively.

PMID- 12060867
TI  - Effect of age on rat bone solubility and crystallinity.
AB  - It has been shown that biominerals such as dental enamel and bone demonstrate a
      non-thermodynamic equilibrium state following initial dissolution where no
      further mineral dissolution or precipitation occurs; this state is termed
      metastable equilibrium solubility (MES). Furthermore, these minerals are composed
      of a distribution of domains each with their own MES. Recent studies have also
      demonstrated a linear relationship between crystallinity and the mean MES of
      these minerals, with solubility decreasing with increasing crystallinity. This
      study investigates the effect of age on the MES and crystallinity of rat bone
      mineral. The bone mineral samples were prepared by protein extraction with a
      series of hydrazine and alcohol solutions. The MES distributions of the bone
      mineral were measured by exposure to 0.1 M acetate buffers containing a range of
      calculated amounts of calcium (Ca) and phosphate for 48 h. The amount of mineral
      dissolved in each solution was determined from Ca and phosphate analyses of the
      undissolved residue. The full width of the half maximum (FWHM) of the 002
      reflection of the X-ray powder diffraction was used as an indicator of
      crystallinity. The MES of mineral from bone of rats of different ages (1-25
      months) were compared. Results of this study indicate that (l) there is a
      difference in the mean MES of bone mineral from rats of different ages, with
      older bone mineral being less soluble and more crystalline than bone mineral from
      younger rats; (2) the nature of the solubility distribution changes from a narrow
      to a broader distribution with age; and (3) all of the bone samples demonstrated
      an inverse-linear correlation between crystallinity and mean MES value consistent
      with previous results obtained with synthetic apatites and dental enamel.

PMID- 12060868
TI  - Nosocomial spontaneous bacterial peritonitis and bacteremia in cirrhotic
      patients: impact of isolate type on prognosis and characteristics of infection.
AB  - The characteristics of and prognosis for nosocomial spontaneous bacterial
      peritonitis (SBP) and bacteremia were examined in a prospective study that
      included data from 194 consecutive episodes of SBP and 119 episodes of
      bacteremia, 93.3% of which were nosocomial, in 200 hospitalized cirrhotic
      patients. Gram-positive pathogens were predominant (70% of the total) among
      isolates from nosocomial infections; the prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) was 24.8%. Nosocomial and staphylococcal infections
      were associated with a higher mortality rate than were community-acquired
      infections (P=.0255) and nonstaphylococcal infections (P<.001), respectively. In
      comparison with non-MRSA infections, MRSA infections were more likely to recur
      and occurred in a greater number of sites other than ascitic fluid and blood
      (P=.0004). Older age (P=.0048), higher Child-Pugh score (P=.0011), and infection
      with staphylococci (P=.0031) were independently associated with a higher
      mortality rate. The emergence of MRSA is important because of the recurrence and
      poor outcome associated with infection with such organisms.

PMID- 12060869
TI  - Health-related quality of life and posttraumatic stress disorder among survivors
      of an outbreak of Legionnaires disease.
AB  - A follow-up study of 122 survivors of an outbreak of legionnaires disease (LD) in
      The Netherlands was conducted to determine persistence of symptoms, health
      related quality of life (HRQL), and presence of posttraumatic stress disorder
      (PTSD). Seventeen months after diagnosis of LD, survivors completed a
      questionnaire assessing symptoms and HRQL and a questionnaire assessing PTSD. The
      most prevalent new symptoms were fatigue (in 75% of patients), neurologic
      symptoms (in 66%), and neuromuscular symptoms (in 63%). HRQL was impaired in 7 of
      the 8 dimensions assessed by the HRQL questionnaire, and 15% of patients
      experienced PTSD. Symptoms and impaired HRQL persisted for >1.5 years. As a
      result of the design of this study, it could not be inferred whether Legionella
      pneumophila infection, severe pneumonia in general, or the outbreak situation was
      responsible for impaired well-being. However, awareness of this problem by health
      care providers may improve the aftercare of patients.

PMID- 12060870
TI  - To gown or not to gown: the effect on acquisition of vancomycin-resistant
      enterococci.
AB  - Infection-control recommendations include the use of gowns and gloves to prevent
      horizontal transmission of vancomycin-resistant enterococci (VRE). This study
      sought to determine whether the use of a gown and gloves gives greater protection
      than glove use alone against VRE transmission in a medical intensive care unit
      (MICU). From 1 July 1997 through 30 June 1998 and from 1 July 1999 through 31
      December 1999, health care personnel and visitors were required to don gloves and
      gowns upon entry into rooms where there were patients infected with nosocomial
      pathogens. From 1 July 1998 through 30 June 1999, only gloves were required under
      these same circumstances. During the gown period, 59 patients acquired VRE (9.1
      cases per 1000 MICU-days), and 73 patients acquired VRE during the no-gown period
      (19.6 cases per 1000 MICU-days; P<.01). The adjusted risk estimate indicated that
      gowns were protective in reducing VRE acquisition in an MICU with high VRE
      colonization pressure.

PMID- 12060872
TI  - Pseudo-outbreak of Mycobacterium fortuitum on a Human Immunodeficiency Virus
      Ward: transient respiratory tract colonization from a contaminated ice machine.
AB  - Infection Control surveillance revealed an abnormally high number of sputum
      samples growing Mycobacterium fortuitum from a single ward that houses the human
      immunodeficiency virus service. We investigated the outbreak using a
      retrospective case-control study and molecular epidemiology. A total of 47
      patients were identified with >/=1 sputum sample that grew M. fortuitum. No
      significant demographic or clinical variables were found to be associated with
      colonization. Environmental investigation demonstrated that the M. fortuitum
      isolated from patients was identical to the ice machine isolates by pulsed-field
      gel electrophoresis. Fortunately, there has been no evidence of progressive
      pulmonary disease developing in our patients after >/=6 months of follow-up. All
      cases were thought to represent transient colonization and not infection. The ice
      machine was disconnected and cleaned successfully with vinegar and then bleach.
      Only when a 0.5-micrometer filter was installed were no further patients
      colonized or water cultures found to be positive.

PMID- 12060871
TI  - Practical aspects of choosing an antibiotic for patients with a reported allergy
      to an antibiotic.
AB  - Physicians often must select antibiotics for patients who are reported to have an
      antibiotic allergy. For penicillins, the sensitivity of penicillin skin testing
      for predicting serious allergic reactions is excellent. For other beta-lactam
      antibiotics, penicillin skin testing is useful for excluding the possibility of
      sensitivity to the beta-lactam ring. For other antibiotics, the patient history
      remains the most useful tool for determining whether a serious reaction is likely
      to occur with further drug exposure. The cross-reactivity between penicillins and
      second- or third-generation cephalosporins (excluding cefamandole) is probably no
      higher than is the cross-reactivity between penicillins and other classes of
      antibiotics. When a patient has a suspected immunoglobulin E-mediated antibiotic
      allergy, desensitization therapy should be considered, if the efficacy of
      alternate antibiotics is in doubt. For the treatment of serious infections, it is
      usually possible to safely administer the antibiotic of choice despite a history
      of possible antibiotic allergy.

PMID- 12060874
TI  - The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity
      in adults with suspected meningitis.
AB  - To determine the diagnostic accuracy of Kernig's sign, Brudzinski's sign, and
      nuchal rigidity for meningitis, 297 adults with suspected meningitis were
      prospectively evaluated for the presence of these meningeal signs before lumbar
      puncture was done. Kernig's sign (sensitivity, 5%; likelihood ratio for a
      positive test result [LR(+)], 0.97), Brudzinski's sign (sensitivity, 5%; LR(+),
      0.97), and nuchal rigidity (sensitivity, 30%; LR(+), 0.94) did not accurately
      discriminate between patients with meningitis (>/=6 white blood cells [WBCs]/mL
      of cerebrospinal fluid [CSF]) and patients without meningitis. The diagnostic
      accuracy of these signs was not significantly better in the subsets of patients
      with moderate meningeal inflammation (>/=100 WBCs/mL of CSF) or microbiological
      evidence of CSF infection. Only for 4 patients with severe meningeal inflammation
      (>/=1000 WBCs/mL of CSF) did nuchal rigidity show diagnostic value (sensitivity,
      100%; negative predictive value, 100%). In the broad spectrum of adults with
      suspected meningitis, 3 classic meningeal signs did not have diagnostic value;
      better bedside diagnostic signs are needed.

PMID- 12060873
TI  - Validity of self-reporting of episodes of external genital warts.
AB  - To determine whether men are able to self-diagnose external genital warts (EGWs),
      we studied data from 1115 men with and without human immunodeficiency virus
      infection. Men were largely unable to accurately assess the presence of EGWs.
      Self-reporting of EGWs was not a sensitive tool; only 38% of men who had EGWs
      diagnosed by a trained examiner who used bright light and visual inspection also
      reported having them. When we controlled for other covariates in a multivariate
      model, men who had EGWs diagnosed by an examiner were 14 times less likely to
      show concordance between examiner findings and self-report than were men who did
      not have EGWs diagnosed by an examiner (odds ratio, 0.07; 95% confidence
      interval, 0.06-0.09). Self-diagnosis and self-assessment may not accurately
      reflect the presence of EGWs, and self-diagnosis should not be used in place of
      an examiner's findings for epidemiologic studies that seek to determine the cause
      of disease.

PMID- 12060875
TI  - The impact of novel immunosuppressive agents on infections in organ transplant
      recipients and the interactions of these agents with antimicrobials.
AB  - Several of the new immunosuppressive agents that are used to treat transplant
      recipients possess in vitro activity against specific pathogens, enhance the
      activity of antimicrobial agents, or have unique drug interactions with
      antimicrobial agents. Mycophenolate mofetil may have a protective effect against
      Pneumocystis carinii; it also enhances the activity of ganciclovir and has strong
      antiviral activity against human immunodeficiency virus type 1. High doses of
      mycophenolate mofetil have been associated with a higher frequency of tissue
      invasive cytomegalovirus disease but not with asymptomatic cytomegalovirus
      infection. Rapamycin exhibits potent in vitro fungicidal activity against
      Cryptococcus neoformans and several pathogenic fungi in transplant recipients;
      however, it is not known whether its immunosuppressive effect in organ transplant
      recipients outweighs its antifungal activity. Recognition of the unique
      characteristics of these agents and the evolving spectrum of opportunistic
      infections has implications for the differential diagnosis, management, and
      prophylaxis of infections in organ transplant recipients in the modern
      immunosuppressive era.

PMID- 12060876
TI  - Intra-abdominal Sepsis in Elderly Persons.
AB  - Elderly patients represent a greater percentage of the population now than ever
      before, with 12.4% of North Americans being >65 years of age. Intra-abdominal
      illnesses in this population often have different etiologies than those seen in
      younger populations. Because of a variety of physiologic changes that occur as
      people age, elderly persons have different sites of infection, may present with
      vague symptoms and longer histories, are more gravely ill, and, overall, have
      worse prognoses. The major causes of intra-abdominal sepsis in elderly persons
      are reviewed, explanations for the differences in presentation and prognosis are
      offered, and the treatments of each cause are reviewed.

PMID- 12060877
TI  - Long-term metabolic consequences of switching from protease inhibitors to
      efavirenz in therapy for human immunodeficiency virus-infected patients with
      lipoatrophy.
AB  - The roles of nucleoside analogues and protease inhibitors (PIs) in the
      development of metabolic complications and fat-distribution abnormalities
      associated with highly active antiretroviral therapy (HAART) are not well known.
      We performed an observational study in which efavirenz was substituted for a PI
      for 41 patients receiving HAART who had prolonged virus suppression, clinical
      signs of severe lipoatrophy, hyperlipidemia, and insulin resistance. Clinical
      follow-up was performed for 1 year. Virus suppression was maintained in most of
      the patients, and a significant increase in CD4(+) lymphocyte count was observed,
      but no change in lipid profile or insulin resistance was observed. Abdominal fat
      content did not change, and subcutaneous fat depletion was even more pronounced
      >1 year after the switch. We conclude that, for PI-treated patients who present
      with lipoatrophy, hyperlipidemia, and insulin resistance, substituting efavirenz
      for PIs can maintain virus suppression and immunologic response to HAART, but it
      does not improve the lipid profile or resolve insulin resistance or lipoatrophy.

PMID- 12060878
TI  - Virus load during primary Human Immunodeficiency Virus (HIV) type 1 infection is
      related to the severity of acute HIV illness in Kenyan women.
AB  - We evaluated the association between the severity of primary human
      immunodeficiency virus type 1 (HIV-1) illness and HIV-1 plasma virus load before
      seroconversion using stored plasma samples obtained from 74 prostitutes in
      Mombasa, Kenya. Fever, vomiting, headache, fatigue, arthralgia, myalgia, sore
      throat, skin rash, or being too sick to work were each associated with
      significantly higher virus loads before HIV-1 seroconversion, and each additional
      symptom or sign was associated with an increase in virus load of 0.4 log(10)
      copies/mL.

PMID- 12060879
TI  - Discordant Human Immunodeficiency Virus Type 1 drug resistance mutations,
      including K103N, observed in cerebrospinal fluid and plasma.
AB  - Discordant resistance mutations were seen in human immunodeficiency virus type 1
      (HIV-1) isolated from specimens of blood and cerebrospinal fluid (CSF) obtained
      from 3 of 6 patients. To our knowledge, this is the first report of HIV-1
      isolated from CSF harboring the K103N mutation, which confers resistance to the
      nonnucleoside reverse-transcriptase inhibitors, and this finding may indicate
      that virus in the CSF replicates independently from virus in the blood
      compartment.

PMID- 12060880
TI  - Suboptimal measles-mumps-rubella vaccination coverage facilitates an imported
      measles outbreak in ireland.
AB  - The year 2000 saw a dramatic increase in the incidence of measles infections in
      Ireland, with >1500 cases documented. Initial cases were reported from an area of
      Dublin with low vaccine uptake and a large immigrant population. Molecular
      epidemiologic findings revealed that the strain of measles virus responsible for
      this outbreak was the genotype D2 strain, which is closely related to strains
      initially identified in South Africa. It is suggested that suboptimal vaccine
      uptake facilitated the spread of imported measles infection.

PMID- 12060881
TI  - Severe pleuropulmonary paragonimiasis 8 years after emigration from a region of
      endemicity.
AB  - A Laotian man who had resided only in the north-central United States for 8 years
      sought care for an acute, progressive syndrome of severe dyspnea, chest pain,
      bilateral pneumothoraces, lung and liver nodules, and marked peripheral blood
      eosinophilia. He habitually ate raw crabmeat imported pickled or frozen from
      Southeast Asia; he denied eating local crustaceans. Ova consistent with the lung
      fluke Paragonimus westermani were identified in a bronchoalveolar lavage
      specimen, and the eosinophilia and pulmonary symptoms resolved with praziquantel
      therapy.

PMID- 12060882
TI  - Use of liver function tests to predict the magnitude of an outbreak of hepatitis
      A.
AB  - The results of liver function tests allowed local and state public health
      professionals in Alaska to accurately predict the magnitude of an outbreak of
      hepatitis A.

PMID- 12060883
TI  - Infections associated with use of the LifeSite Hemodialysis Access System.
AB  - We observed infection rates associated with the LifeSite Hemodialysis Access
      System, a novel dialysis device consisting of 2 subcutaneously implanted valves
      accessed by repeated use of fibrous tissue tracts, of 4.8 total infections and
      8.1 first episodes per 1000 patient-days. These rates are higher than those
      observed elsewhere, which may be related to use of the device in a population of
      chronically ill patients, to the learning curve associated with use of the
      device, or to inherent qualities of the device.

PMID- 12060884
TI  - Hypophyseal hemorrhage and panhypopituitarism during Puumala Virus Infection:
      Magnetic Resonance Imaging and detection of viral antigen in the hypophysis.
AB  - We describe 3 cases of nephropathia epidemica (NE) that confirm that Puumala
      virus infection may cause hypophyseal injury. Autopsy revealed a hemorrhagic
      hypophysis positive for Puumala virus antigen in both neuroendocrine stromal and
      vascular endothelial cells in 1 patient, and 2 patients developed hypophyseal
      hemorrhage (diagnosed with magnetic resonance imaging) during or shortly after
      acute NE, both of whom developed panhypopituitarism.

PMID- 12060885
TI  - An Outbreak of Varicella among children attending preschool and elementary school
      in Illinois.
AB  - In our investigation of a varicella outbreak among students in preschool,
      kindergarten, and grades 1-3 in Winnebago County, Illinois, we found an overall
      varicella vaccine efficacy of 88%, evidence that the circulating virus was a wild
      type strain (as determined by polymerase chain reaction analysis), and evidence
      that vaccination of children </=15 months of age was associated with an increased
      risk for breakthrough varicella (relative risk, 3.7; 95% confidence interval, 1.1
      13.1; P=.04). The efficacy of varicella vaccine might be improved if
      administration of the initial vaccine dose is delayed until children are >/=15
      months of age.

PMID- 12060886
TI  - The gastrointestinal tract is a common target of invasive aspergillosis in
      patients receiving cytotoxic chemotherapy for hematological malignancy.

PMID- 12060888
TI  - Caspofungin versus amphotericin B for the treatment of Candidal esophagitis.

PMID- 12060890
TI  - Deep-seated trichosporonosis in an immunocompetent patient: a case report of
      uterine trichosporonosis-correction.

PMID- 12060892
TI  - Nosocomial Infections with Aeromonas hydrophila from Leeches.
AB  - The manner in which leeches are maintained before they are used for therapy has
      not been studied as a factor contributing to nosocomial infections. A 5-year
      retrospective survey of Aeromonas hydrophila nosocomial infections at a hospital
      in Marseille, France, revealed infections in 5 (4.1%) of an estimated 122
      patients treated with leeches in the Hand Surgery Unit and 2 (2.4%) of an
      estimated 85 patients treated with leeches in other hospital units. The
      retrospective survey showed that the Hand Surgery Unit was the only unit that had
      its own aquarium for maintaining leeches; this aquarium was filled with tap water
      contaminated with Aeromonas species and was not regularly disinfected or cleaned.
      Leeches used in other units were maintained in noncarbonated water in a transport
      device. Use of leeches kept in aquariums that are filled with tap water and not
      disinfected or cleaned regularly may be linked to A. hydrophila infections.

PMID- 12060893
TI  - Legionella pneumophila Arthritis: use of medium specific for Mycobacteria for
      isolation of L. pneumophila in culture of articular fluid specimens.
AB  - We report the first case, to our knowledge, of acute purulent arthritis due to
      Legionella pneumophila in an immunosuppressed patient. L. pneumophila was
      isolated from samples of blood and articular fluid cultured with use of medium
      specific for mycobacteria (Bactec 13A medium).

PMID- 12060894
TI  - Localized osteomyelitis due to Mycobacterium avium complex in patients with Human
      Immunodeficiency Virus receiving highly active antiretroviral therapy.
AB  - We describe 3 patients who developed atypical manifestations of Mycobacterium
      avium complex (MAC) infection >10 months (range, 3-16 months) after attaining
      sustained CD4(+) T cell counts of >100 cells/microL while receiving
      antiretroviral therapy and not receiving MAC prophylaxis. The common features of
      these cases include the degree of immune reconstitution, the unusual locations of
      the infections, and the absence of a systemic inflammatory response. The low rate
      of these unusual MAC infections does not warrant continuation of primary or
      secondary prophylaxis after presumed immune reconstitution.

PMID- 12060896
TI  - Is acute type A aortic dissection a true surgical emergency?
AB  - Untreated acute aortic dissection involving the ascending aorta (type A) is
      associated with a high early mortality owing to rupture. Despite advancements in
      surgical technique and critical care, early mortality remains high. Operative
      mortality may be related to the technical challenges associated with intervening
      on the acutely dissected aorta as well as the multiorgan insult it induces. In
      this article, we review our approach to acute type A aortic dissection with
      regard to diagnosis, initial medical management, surgical repair, and timing of
      repair.

PMID- 12060897
TI  - Descending thoracic aortic dissection: clinical aspects and anatomic
      correlations.

PMID- 12060898
TI  - Acute aortic dissection with side branch vessel occlusion: open surgical options.
AB  - Acute aortic dissection is one of the most common catastrophes affecting the
      aorta. Because dissection can involve any aortic segment, the disease can
      manifest itself through a variety of clinical presentations. The most spectacular
      manifestation is frank rupture, usually into the pericardial or pleural cavity.
      Dissections of the ascending aorta are associated with rapidly fatal
      complications such as cardiac tamponade, major stroke, or massive myocardial
      infarction, justifying emergent operation. Dissections of the descending aorta
      are managed medically with surgery reserved for those patients with aortic
      rupture, aneurysmal dilatation, or ischemic symptoms. Aortic branch occlusion
      occurs in up to one third of patients with aortic dissection and is associated
      with increased risk of early death and serious complications. The therapeutic
      armamentarium of the vascular surgeon has evolved during the last 20 years to
      include endovascular (balloon fenestration or branch stenting) and surgical
      options. This article will focus on the open surgical management of patients with
      acute aortic dissection complicated by side branch occlusion and organ or limb
      malperfusion.

PMID- 12060899
TI  - Surgical treatment of complicated distal aortic dissection.
AB  - Among the various treatment options for acute distal dissection with aortic
      branch compromise, we have favored open vascular surgical techniques. Our
      perspectives with over 500 patients treated during a 30-year period are presented
      herein.

PMID- 12060901
TI  - Aortic dissection with branch vessel occlusion: percutaneous treatment with
      fenestration and stenting.
AB  - Aortic dissection involves a tear in the intimal and medial layers of the aortic
      wall. Early surgical treatment of this condition can be fraught with
      complications especially when the procedure to be performed involves treatment of
      renal and visceral vessels. Additionally, patients with this problem can have
      severe compromise of the flow to branches or the entire aortic distribution.
      Methods of endovascular therapy for these problems limit the surgical stress and
      often can be performed in less time than surgical revascularization might
      require. The use of endovascular stenting to improve vessel perfusion and
      fenestration of the dissection membrane to decrease pressure within the false
      lumen can be performed to relieve ischemic vascular beds and potentially decrease
      the risk of aneurysmal dilatation of the aorta. The increasing use of these
      techniques may allow stabilization of these patients before open repair of more
      proximal aortic dissection or a combination of therapy with endovascular stent
      grafting techniques.

PMID- 12060900
TI  - The effect of aortic dissection on outcome in descending thoracic and
      thoracoabdominal aortic aneurysm repair.
AB  - It is estimated that 20% to 40% of the patients who survive the acute phase of
      aortic dissection will develop significant aneurysmal dilatation of the
      descending thoracic or thoracoabdominal aorta. Aortic dissection has long been
      considered a risk factor for mortality and neurologic deficit following surgical
      repair of the descending thoracic and/or thoracoabdominal aorta. In this article
      we review the surgical approach to patients with aortic dissection and
      thoracoabdominal aortic aneurysms and discuss the impact of adjuncts on survival
      and neurologic outcome.

PMID- 12060902
TI  - Treatment of aortic dissections with endovascular stent grafts.
AB  - The management of aortic dissections remains controversial. Knowledge regarding
      the extent and specific pathophysiology of each dissection is critical prior to
      intervention. Cross-sectional imaging techniques coupled with intravascular
      ultrasound or hemodynamic measurements are vital. In the setting of ischemia with
      significant true lumen compromise, the placement of a proximal endovascular graft
      has a high likelihood of dramatically improving the diameter of the true lumen,
      alleviating distal ischemia. Caution must be taken when branch vessels are
      involved in the dissection. Adequate true lumen flow with persistent end-organ
      ischemia is best handled with branch vessel stenting. Combined true lumen
      compresssion and branch vessel dissection requires both visceral vessel stenting
      and proximal endovascular grafting. Using these techniques, we have been able to
      achieve a mortality rate of less than 35% in a patient population that previously
      suffered mortality rates in excess of 50%. However, application of these
      technologies to asymptomatic or nonischemic dissections is not warranted outside
      the context of investigational trials.

PMID- 12060904
TI  - Carotid artery dissection.

PMID- 12060903
TI  - Spontaneous dissection of the infrarenal abdominal aorta.
AB  - Spontaneous infrarenal abdominal aortic dissection is rare. We observed
      enlargement of a spontaneous infrarenal aortoiliac dissection in a 55-year-old
      hypertensive man. Open surgical repair with a bifurcated polyester graft was
      successful. A review of the English literature found 41 previously published
      cases. Mean age was 58 years, 74% of the patients were male, and 62% had
      hypertension. None had Marfan or Ehlers-Danlos syndrome. More than three fourths
      of the patients had symptoms, 6 patients (14%) presented with aortic rupture.
      Dissection was limited to the infrarenal aorta in 50% and extended into the iliac
      or femoral arteries in 50%. Three patients died before treatment, no death
      occurred after endovascular repair of after elective open aortic grafting.
      Mortality following rupture was 67%. Abdominal aortic dissection did not reoccur
      but 1 patient died at 14 month because of rupture of a thoracic aneurysm.
      Spontaneous infrarenal abdominal aortic dissections are rare, but usually
      symptomatic and 14% rupture. Rupture carries high mortality. Elective open repair
      is recommended, but endovascular repair is a new treatment option for suitable
      patients.

PMID- 12060905
TI  - The epidemiology of valvular heart disease: an emerging public health problem.

PMID- 12060906
TI  - Percutaneous mitral balloon valvuloplasty. Does it really last as long and do as
      well as surgery?

PMID- 12060907
TI  - Mitral commissurotomy and valve replacement for mitral stenosis: observations on
      selection of surgical procedures.

PMID- 12060908
TI  - Mitral regurgitation: natural history in operated and unoperated patients.

PMID- 12060909
TI  - Complications of mitral valve prolapse.

PMID- 12060910
TI  - Mitral regurgitation: predictors of outcome and natural history.

PMID- 12060911
TI  - Importance of right ventricular performance measurement in selecting asymptomatic
      patients with mitral regurgitation for valve surgery.

PMID- 12060912
TI  - Emerging biology of mitral regurgitation: implications for further therapy.

PMID- 12060913
TI  - Mitral valve repair for ischemic mitral regurgitation.

PMID- 12060914
TI  - Concomitant mitral repair at the time of coronary artery bypass grafting--the
      'con' point of view.

PMID- 12060915
TI  - Minimally invasive valve surgery: evolution of technique and clinical results.

PMID- 12060917
TI  - Emerging role of complementary medicine in valvular surgery.

PMID- 12060916
TI  - Blood conservation: is it working?

PMID- 12060918
TI  - Factors determining selection of valve prosthesis--tissue or mechanical: current
      status.

PMID- 12060919
TI  - Selective aspects of infective endocarditis: considerations on diagnosis, risk
      factors, treatment and prophylaxis.

PMID- 12060920
TI  - Echocardiographic assessment of the vegetation: are there characteristics that
      mandate prophylactic surgical intervention?

PMID- 12060921
TI  - Aortic valve disease--etiology and the role of vascular pathology: is the face of
      the disease changing?

PMID- 12060922
TI  - Atrial fibrillation and valve disease.

PMID- 12060923
TI  - Selection of patients with aortic stenosis for operation: the asymptomatic
      patient and the patient with poor LV function.

PMID- 12060924
TI  - The value of myocardial perfusion imaging for diagnosing coronary artery disease
      in patients with aortic valve stenosis.
AB  - Angina is a common symptom in patients with AS with or without accompanying CAD.
      When due to the valvular obstruction alone, the pathophysiology involves mismatch
      between reduced diastolic coronary flow and increased LV mass, or impaired
      coronary vasodilator reserve. When CAD is present, the severity of angina
      correlates with the extent of CAD, which tends to be inversely related to the
      degree of valvular obstruction at presentation. It is important to make a correct
      diagnosis of CAD in AS patients pre-operatively, since this factor significantly
      influences peri-operative morbidity and long-term survival. Whether MPI in AS
      patients can completely exclude CAD and eliminate the need for coronary
      angiography is a difficult question. Approximately 350 AS patients having had MPI
      have been reported. The studies differ in terms of scintigraphic technique
      (planar versus SPECT), stress modality, isotopes used, and definitions of an
      abnormal scan and what constitutes hemodynamically significant coronary stenosis.
      The 'best case' diagnostic data showed sensitivity of 87%, specificity 72%,
      positive predictive value of 81%, and negative predictive value of 86%. These
      figures indicate a high degree of accuracy and are comparable to the results of
      MPI in patients without AS. However, the data suggest that the diagnosis of
      coronary disease is missed by MPI in 14% of AS patients with CAD. Review of the
      referenced series indicates that in many cases, the stenoses were hemodynamically
      significant, and were important to identify pre-operatively to avoid operative
      morbidity and improve long-term prognosis. Thus, in conclusion, although MPI is
      highly accurate in AS patients, a normal study cannot totally exclude the
      diagnosis of CAD. Coronary angiography should continue to be performed,
      particularly in patients with angina, or who are at risk for CAD because of their
      risk factor profile.

PMID- 12060925
TI  - The cellular and molecular basis of heart failure in regurgitant valvular
      diseases: the myocardial extracellular matrix as a building block for future
      therapy.

PMID- 12060926
TI  - Congenital aortic stenosis: is repair an option?

PMID- 12060927
TI  - Aortic regurgitation: selection of asymptomatic patients for valve surgery.

PMID- 12060928
TI  - Surgical approaches when aortic regurgitation is associated with aortic root
      disease.

PMID- 12060929
TI  - Technique and results of the modified Ross procedure in aortic regurgitation
      versus aortic stenosis.

PMID- 12060930
TI  - Profit. The least-used word in medicine.

PMID- 12060931
TI  - MGMA expresses support for medical privacy changes.

PMID- 12060932
TI  - Physician compensation changes with experience.

PMID- 12060933
TI  - Satisfied employees=satisfied patients, smoother operations. A medical staff
      training program case study.

PMID- 12060934
TI  - He says, she says. Gender differences a powerful force in the workplace.

PMID- 12060935
TI  - Where the deer and the antelope play.... Rural health centers face tough
      challenges.

PMID- 12060936
TI  - Allow options, not variations, in EMR use. A multispecialty group's experience
      with electronic medical records.

PMID- 12060937
TI  - Creating a Web presence for your practice. A primer.

PMID- 12060938
TI  - Medical malpractice cost crisis hits hard. No state or specialty will be spared,
      experts say.

PMID- 12060939
TI  - 10 key factors to improve operations in ambulatory surgery centers.

PMID- 12060940
TI  - Culture of nursing, preoccupation with prediction, and nursing intention.
AB  - Culture is a series of rules and methods that a society has evolved to deal with
      the recurring problems it faces. These have become so basic that, like breathing,
      we no longer think about how we approach or resolve them.

PMID- 12060941
TI  - Intentionality and caring-healing consciousness: a practice of transpersonal
      nursing.
AB  - This article explicates some theoretical and scientific dimensions of
      intentionality and consciousness as a framework for transpersonal nursing. New
      connections are made between noetic sciences and transpersonal caring theory,
      both of which cultivate intentionality as a form of focused consciousness as a
      formal field of study. What emerges is Intentional Transpersonal Caring, whereby
      intentionality, consciousness, and universal energy-field are posited as the
      foundation of a caring moment, potentiating healing for both practitioner and
      patient. The theoretical and scientific are translated into the practical by a
      series of practice guidelines that activate intentionality into a living theory
      of transpersonal caring-healing praxis.

PMID- 12060942
TI  - Hands-on: the persistent metaphor in nursing.
AB  - The metaphor "hands-on" has been used throughout the history of nursing,
      highlighting internal conflict and reflecting the centrality of patient care.
      Connection with the intent to heal suggests the deeper meaning of the metaphor.
      Nurses have struggled to maintain a holistic approach to patient care while
      reflecting larger social values. Some nurses have moved from holistic care of the
      client to a holistic use of self as healer. This unified approach of head, heart,
      and hands is exemplified in healers using touch therapies. Head and heart unite
      with the action of the hand with intent to heal.

PMID- 12060943
TI  - Choosing personhood: intentionality and the theory of nursing as caring.
AB  - Drawing on a story of a nursing situation for practical context, this article
      explores the meaning of intentionality within the theoretical context of Nursing
      as Caring. May's definition of intentionality as the structure that gives meaning
      to experience is interwoven with the concepts of the theory of Nursing as Caring
      to explore the topic. Mayeroff's concepts of hope and commitment contribute to an
      understanding of intentionality in relation to Nursing as Caring. The major
      thesis of this article, that intentionality is consistently choosing personhood
      as a way of life and the aim of nursing, is demonstrated in the practice
      situation.

PMID- 12060944
TI  - Balance and harmony through connectedness: the intentionality of Native American
      nurses.
AB  - This article describes how Native American nurses facilitate and promote harmony
      and balance through connectedness. According to the Conceptual Framework of
      Nursing in the Native American Culture, connectedness is at the core of
      intentionality of Native American nurses. Connectedness occurs through the
      dynamics of an interdependent and interrelated relationship between the nurse and
      client. The worldview of Native Americans is illuminated and illustrated within
      the context of culturally congruent nursing interventions.

PMID- 12060945
TI  - Intentionality: applications within selected theories of nursing.
AB  - Intentionality is an important concept for nurses to study for professional and
      theoretical reasons. Lewis states that intentionality is best studied within an
      active, rather than reactive, worldview. This article is a level-by-level outline
      of Lewis' five-level model for the study of intentionality. These levels are:
      necessity, interactive necessity, action intent, divergent intent, and conscious
      intent. Newman's tri-part categorization of nursing theory paradigms
      (particularate-deterministic, interactive-integrative, and unitary
      transformative) proves to be a useful framework to compare the Lewis model of
      intentionality with nursing theory. Examples from nursing theory development,
      such as the Roy adaptation model, chronotherapeutics, Rogers' theory of unitary
      human being, health as expanding consciousness, and therapeutic touch, are used
      to support all five levels of intentionality in providing guidance for practice
      and research by nurse theorists.

PMID- 12060946
TI  - Tellington touch before venipuncture: an exploratory descriptive study.
AB  - Tellington touch (ttouch) is an emerging natural healing modality used by nurses
      and other health care providers to communicate caring and connection to clients.
      This simple-to-learn and easy-to-implement form of mindful, gentle physical touch
      is said to help in diverse areas such as chronic pain management, labor
      discomfort, and postinjury pain and edema. Despite 15 years of anecdotal evidence
      outlining reported benefits for humans, no investigation of ttouch has yet been
      undertaken. This qualitative study initiates a body of knowledge about ttouch by
      exploring and describing the experience of ttouch when administered to healthy
      people awaiting a routine venipuncture. The study includes qualitative data from
      both the participants (n = 47) and the provider (n = 1) and provides essential
      foundational information regarding the experience of ttouch. Implications for
      practice and future research are provided.

PMID- 12060947
TI  - Primary health care: a framework for policy development.
AB  - Primary health care has utility for policy development at all levels of
      organization in any nation, including policies influencing the health of persons
      living with severe and persistent mental illnesses. Using the primary health care
      framework, policies to improve health and housing for this population evolve from
      intersectoral collaboration. Active participation by those persons whose
      essential health is compromised by housing that is not acceptable, adequate,
      suitable, and affordable is required. Appropriate and affordable methods that
      address health challenges are identified. Access to services meeting essential
      health care needs of citizens has potential for healthy outcomes.

PMID- 12060948
TI  - Humor as the focal point of treatment for forensic psychiatric patients.
AB  - Framed as a qualitative case study based on constructivist notions, the research
      being reported evaluates the Humor Group, a unique treatment modality evoking
      therapeutic change by engaging male forensic psychiatric patients and nursing
      students in humorous activities. The group's meaning for patient health was
      investigated by cross-analyzing data collected from patient and student
      questionnaires, in-depth patient interviews, and naturalistic observations made
      by the researcher during the group's 4-year tenure. The Humor Group structure and
      format are offered as guides for undertaking similar attempts to rein in humor's
      healing potential in other settings and with other populations.

PMID- 12060949
TI  - Expanding holistic nursing to the community-as-client.

PMID- 12060950
TI  - Feminist spirituality and alcohol treatment.
AB  - Although there is some evidence that spirituality may play a role in successful
      resolution of alcohol problems, there are those who assert that traditional
      androcentric theologies may be detrimental to the healing process among women.
      Within conventional religious traditions, women have been relegated to positions
      of diminished status and power and may be subject to expectations of self
      abnegation. For these reasons, asserting powerlessness and abdicating control to
      a male-defined deity may be nontherapeutic. In contrast, feminist spirituality
      represents a collage of traditions that enable women to identify the divine
      within and find strength and power through their interpersonal relationships and
      lived experiences. Together, the foci of feminist spirituality and women's health
      care provide new perspectives for alcohol treatment. Nurses need to become aware
      of these viewpoints and ways in which they can be integrated into their
      practices.

PMID- 12060951
TI  - A holistic approach to risk-screening in pregnancy with Appalachian women.
AB  - Routine screening for risk factors in pregnancy is one of the major components of
      prenatal care that is highly recommended, yet few risk assessment systems have a
      comprehensive view. This investigation examined prenatal risk assessment from a
      comprehensive perspective to identify biophysical, psychosocial, spiritual, and
      perceptual factors in pregnancy affecting infant birth weight. Face-to-face
      interviews were conducted using standard and reliable questionnaires with a
      convenience sample of 120 pregnant women between the ages of 14 and 44 years and
      16 to 28 weeks gestation at three prenatal clinics in East Tennessee. Two
      factors, absence of maternal partner support during pregnancy and African
      American race, emerged as significant predictors for infant birth weight.
      Findings emphasize the necessity for nurses and other providers to screen for
      presence and source of social support during routine prenatal assessments.
      Continued research to develop a comprehensive assessment of risk in pregnancy
      should enhance our understanding of maternal factors influencing maternal and
      infant health.

PMID- 12060952
TI  - e-Community health nursing.
AB  - Dissolving boundaries of space and time, the Internet creates another dimension
      in which to practice community health nursing. Addressing the challenges of
      health issues in the virtual environment affords new opportunities for holistic
      nursing practice. Grounded in holistic nursing theory and practice and built on a
      feminist foundation, this article explores the process of community health
      nursing within an Internet-based community. A brief review of the literature
      identifies relevant research findings. Barriers to communication are identified.
      These include perceived ease of use of computer technology and gendered patterns
      of communication. Lessons learned in an actual Internet community are discussed.

PMID- 12060953
TI  - Relationships among perceived enactment of autonomy, self-care, and holistic
      health in community-dwelling older adults.
AB  - The purpose of this article is to report findings from two studies of community
      dwelling older adults. The focus of both studies was on delineating relationships
      among perceived enactment of autonomy (PEA) and selected self-care and health
      variables from the perspective of Modeling and Role-Modeling nursing theory.
      Results indicated that PEA, representing the potential for self-care action, was
      positively correlated to perceived control and morale in Study 1 and to life
      satisfaction in Study 2. Significant differences in PEA scores were found based
      on the health indicators of participation in social activities and reliance on
      others for shopping in Study 2. In addition, Study 1 found that morale, gender,
      age, perceived control, and education accounted for 39% of the variance in PEA.
      Implications are discussed for designing theory-based holistic nursing
      interventions to support PEA in older adults and to direct future research.

PMID- 12060954
TI  - Applied concepts of holistic nursing. Experiencing the death of my mother. A
      daughter and nurse's perspective.
AB  - As a nurse, I have witnessed the miracle of birth and the sadness of death. The
      death of my mother was one of the most profound experiences I have ever
      encountered. The lessons I learned through this event made me more sensitive to
      the needs of patients and their families. The purpose of this story is to offer
      hope and encouragement to others who may be suffering the loss of a parent and to
      provide reminders and suggestions for nurses who attend to the needs of the dying
      with an emphasis on communication, presencing, and advocacy.

PMID- 12060955
TI  - Outbreak of Salmonella paratyphi B linked to aquariums in the province of Quebec,
      2000.

PMID- 12060956
TI  - The use of osteotomes: a viable alternative to traditional drilling.

PMID- 12060957
TI  - Teenage births in the United States: state trends, 1991-2000, an update.
AB  - OBJECTIVES: This report provides State-specific birth rates for teenagers for
      1991 and 2000, and the percent change between the time periods. METHODS: Tabular
      and graphical description of trends in teenage birth rates by age group for each
      State and territory. RESULTS: Birth rates for teenagers 15-19 years declined
      significantly in all States, the Virgin Islands and Guam, between 1991 and 2000.
      Declines by State ranged from 12 to 39 percent. Rates also fell significantly for
      teenage subgroups 15-17 and 18-19 years.

PMID- 12060958
TI  - The Ten Commandments of effective budgeting.

PMID- 12060959
TI  - Oral infections: impact on human health, well-being, and health-care costs.
AB  - Both caries and periodontal disease as well as many diseases of the mucous
      membranes, tongue, and salivary glands are infectious. If left untreated or
      inadequately treated, they have profound systemic as well as local effects.
      Maintenance of oral health goes beyond the physiological needs of proper
      nutritional intake and protection of the oral tissues. It also includes
      protection against oral sources of systemic infection and encompasses a range of
      social and psychological attributes. The rising expectations of patients in the
      pursuit of comfort and esthetics has provided evidence of the oral contribution
      to quality of life. Oral infections and their sequela account for the major
      portion of annual dental expenditures.

PMID- 12060960
TI  - Nutrition and oral infectious diseases: connections and future research.
AB  - A workshop on nutrition and oral infectious diseases was held November 5-7, 2000
      at the Forsyth Institute, Boston, Massachusetts. The goal of the symposium was to
      review the current state-of-the-science with regard to nutrition and oral
      infectious diseases (particularly periodontitis) and then connect the disciplines
      of nutrition, microbiology, immunology, and clinical periodontology through a
      comprehensive list of recommendations for future research. The workshop featured
      five scientific sessions (oral infections and general health, research models,
      nutrition and infection, nutrition and oral infection, and nutrition, oral
      health, and life cycle). An agenda with the complete list of speakers together
      with the recommendations can be found at
      http://www.forsyth.org/nutrition/recommendations.htm. A brief summary of the
      workshop is presented in this article.

PMID- 12060961
TI  - The frenectomy as an adjunct to periodontal treatment.

PMID- 12060962
TI  - Nutrition and oral infectious diseases: state of the science.
AB  - Immunological competence and nutritional status are two of the most important
      determinants of morbidity and mortality. Oral diseases, particularly inflammatory
      periodontal lesions, are caused by viruses and specific periodontopathic
      bacteria. Paradoxically, the production of cytokines and oxidant molecules, which
      are supposed to be part of a highly effective mechanism for combating the
      periodontal pathogens, may damage the host. Malnutrition consistently impairs
      innate and adaptive defenses of the host, including phagocytic function, cell
      mediated immunity, complement system, secretory antibody, and cytokine production
      and function. In protein-energy malnutrition, there are marked changes in the
      oral microbial ecology resulting in a preponderance of pathogenic anaerobic
      organisms, increased propensity of bacteria to bind to oral mucosal cells,
      attenuation of acute phase protein response, and dysfunction of the cytokine
      system. Cellular depletion of antioxidant nutrients promotes immunosuppression,
      accelerated replication rate of ribonucleic acid viruses, and increased disease
      progression. Therefore, malnutrition can intensify the severity of oral
      infections and may lead to their evolution into life-threatening diseases.

PMID- 12060963
TI  - Advances in ceramic restorations. Interview by Mark J. Friedman.

PMID- 12060964
TI  - The oral/dental/craniofacial complex as a model for inflammatory disease.
AB  - Many inflammatory diseases, including periodontitis, are the result of
      uncontrolled destruction of host tissues by the host's own inflammatory response.
      Periodontitis as well as other inflammatory diseases are initiated by bacteria
      that results from host cell-mediated tissue destruction. The study of
      inflammation of the oral cavity and craniofacial complex provides an excellent
      window to the understanding of more complex and difficult to study conditions. In
      this article, the inflammatory process in periodontitis is reviewed with an
      emphasis on control pathways that naturally limit inflammation.

PMID- 12060965
TI  - Accelerated control of rubella and prevention of congenital rubella syndrome,
      Brazil.

PMID- 12060966
TI  - Human monocyte stimulation by experimental whole body hyperthermia.
AB  - The thermal effect of fever, an evolutionarily conserved acute-phase response,
      has been associated with better survival and a shorter duration of disease in
      cases of infection. The molecular consequence of this beneficial fever response
      is poorly understood. To determine the influence of hyperthermia on human
      monocytes, which are important for the recognition and elimination of pathogens,
      twelve healthy volunteers were immersed in a 39.5 degrees C hot water bath to
      increase their body temperature. The expression of the endotoxin receptor CD14
      and the complement receptor CD11b increased after the hot water bath (P < 0.05),
      whereas the expression of the selectin CD62L, which mediates the initial
      attachment of leukocytes at the endothelium during inflammation, was
      downregulated after hyperthermia (P < 0.05). Comparable changes in monocyte
      receptor expression were observed after in vitro hyperthermia. Furthermore, 3
      hours after in vivo hyperthermia, the response of monocytes to endotoxin was
      enhanced in an ex vivo lipopolysaccharide stimulation assay, as expressed by a
      greater TNF-alpha release (P < 0.05). We conclude that the thermal effect of
      fever directly activates monocytes, which increases their ability to respond to
      bacterial challenge.

PMID- 12060967
TI  - Regional citrate anticoagulation using a citrate-based substitution solution for
      continuous venovenous hemofiltration in cardiac surgery patients.
AB  - OBJECTIVE: To evaluate the feasibility, efficacy, safety and side effects of
      routinely performed continuous venovenous hemofiltration (CVVH) with regional
      citrate anticoagulation using a citrate-containing substitution solution as
      compared with conventional systemic low-dose unfractionated heparin
      anticoagulation in postoperative cardiac surgery patients. DESIGN/SETTING:
      Database review of all patients on CVVH during a three-year period at a
      cardiovascular intensive care unit of a tertiary referring university hospital.
      PATIENTS: Patients who had undergone cardiac surgery with acute or chronic renal
      failure were studied. Thirty-seven citrate CVVH courses in 31 patients (January
      to November 2000) and 59 heparin CVVH courses in 50 patients (1998 and 1999) had
      been undertaken postoperatively. Indications for hemofiltration were acute renal
      failure in 24 and chronic renal failure in 7 of the citrate patients, and acute
      renal failure in 44 and chronic renal failure in 6 of the heparin patients.
      INTERVENTIONS: CVVH with either regional citrate anticoagulation using a custom
      made citrate-based substitution solution or unfractionated heparin
      anticoagulation. MEASUREMENTS: The following parameters were measured: median
      filtration time, hemofilters used per day, differences in creatinine and blood
      urea levels as opposed to baseline, blood loss within the first 24 h of
      hemofiltration, incidence of bleeding-related resternotomies, acidosis, and
      alkalosis. RESULTS: No significant differences in any of the measured parameters
      were registered. No serious electrolyte imbalance was observed in either group.
      Furthermore, the two groups did not differ in terms of mortality, duration of
      stay in the intensive care unit or in hospital, and restoration rate of normal
      renal function. CONCLUSIONS: We conclude that citrate-based regional
      anticoagulation is effective, safe and easy to use in CVVH following cardiac
      surgery and might become the first choice for anticoagulation in patients in whom
      the application of systemic heparin is contraindicated.

PMID- 12060969
TI  - [In memory of Karl Steinbereithner].

PMID- 12060968
TI  - Hypertrophic osteoarthropathy caused by PGE1 in a patient with congestive heart
      failure during cardiac rehabilitation.
AB  - Continuous chronic drug infusion with PGE1 via a portable pump and neuromuscular
      electrical stimulation (NMES) help to improve the quality of life in patients
      with severe chronic heart failure waiting for a donor heart, as both treatments
      can be performed at home. We report a 56-year-old woman suffering from severe
      chronic heart failure, who was referred for a cardiac rehabilitation program
      because of progressive muscle weakness and weight loss. Due to her underlying
      heart disease she was unable to perform voluntary exercise. NMES of both knee
      extensor muscles was started. Under simultaneous chronic drug infusion with PGE1
      via a portable pump the patient developed clinical signs of hypertrophic
      osteoarthropathy, which prevented her from continuing the rehabilitation program.
      X-ray examinations and bone scans concurred with the diagnosis of secondary
      hypertrophic osteoarthropathy. After the PGE1 dose had been reduced, the clinical
      signs of the osteoarthropathy resolved and the patient was able to continue the
      rehabilitation program with no difficulty. This case report underlines the
      importance of being aware of the potential side effects of modern cardiac drugs
      in the complex treatment of patients waiting for a donor heart.

PMID- 12060970
TI  - Fever in acute disease--beneficial or harmful?

PMID- 12060971
TI  - Small-volume resuscitation with hypertonic sodium colloid solution--what does
      clinical routine tell us?

PMID- 12060972
TI  - [Anticoagulation in continuous renal replacement procedures].

PMID- 12060973
TI  - [Fever in acute illness: beneficial or harmful?].
AB  - Fever has had a long phylogenetic history: it occurs not only in infected birds
      and mammals, but also in infected reptiles, amphibians, fish and even insects.
      When these "cold-blooded" animals are prevented from adapting their body
      temperature to the risen thermoregulatory set-point by behavioral means, a more
      severe state of disease and a higher mortality are the consequences. It seems
      unlikely that an energy-dependent process, such as fever, would have been
      retained for hundreds of millions of years, in so many groups of organisms, if it
      provided no selective advantage. Fever may represent a leukocyte-based
      amplification mechanism to affect host challenge: enhanced motility of
      leukocytes, enhanced lymphocyte response to mitogens, increased production of
      interferon, enhanced immune response to viral antigens. Evidence for a beneficial
      effect of fever is also supported by the results of our animal experiments.
      Intraperitoneal injection of a high dose of bacterial lipopolysaccharide (LPS) in
      rats induces a septic shock like state which is accompanied by hypothermia on the
      day of LPS-administration and a robust fever on the following days. Co-injection
      of a neutralizing synthetic form of the soluble tumor necrosis factor (TNF) type
      1 receptor completely neutralizes LPS-induced bioactive TNF in the lavage of the
      abdominal cavity and in blood plasma. Treatment with the TNF-antagonist results
      in much faster recovery from the hypothermic state. The rats develop pronounced
      fever already on the day of injection and there is significantly less reduction
      in body weight and food and water intake. Similar, but less pronounced effects
      can be induced by treatment with inhibitors of the inducible form of nitric oxide
      (NO)-synthase indicating that TNF-induced detrimental effects are, in part,
      mediated by excessive formation of NO. These results confirm that an accelerated
      onset of fever or a faster recovery from hypothermia in a septic state may have
      rather beneficial than maladaptive effects.

PMID- 12060974
TI  - Safety of hypertonic hyperoncotic solutions--a survey from Austria.
AB  - BACKGROUND: Hypertonic hyperoncotic solutions (HHS), composed of 7.2 to 7.5%
      sodium chloride and 6 to 10% dextran or hydroxyethyl starch, are able to restore
      the disturbed macro- and microcirculation in hypovolemic states within a short
      period of time. Even small amounts of HHS induce a relevant fluid shift from the
      extravasal into the intravasal space, and the use of HHS has thus been
      recommended in acute hypovolemia and hypovolemic shock (principle of "small
      volume resuscitation"). Recently, attention has also focused on the treatment of
      elevated intracranial pressure using HHS. Austria is the only European country
      where market authorization of HHS was already obtained several years ago and
      where HHS have been widely used in clinical routine for a comparatively long
      time. This offers the unique possibility of evaluating, for the first time, the
      safety profile of HHS solutions. In this study, we analyzed the reported adverse
      drug reactions of HHS in a large number of applications. METHODS: Marketing and
      pharmacovigilance data as well as other relevant information obtained in Austria
      during the years 1991 to 2000, were used for analysis of safety aspects of HHS
      applications in routine clinical practice. RESULTS: From 1991 to 2000, four
      adverse drug reactions related to HHS were reported, none of which was fatal. Out
      of these, 3 have to be regarded as anaphylactoid/anaphylactic reactions to
      hydroxyethyl starch. In one case an extreme overdose was infused resulting in a
      hyperosmolar syndrome. In the same time period approximately 56,000 HHS units
      were used in Austria in about 18,500 to 37,000 patients. With these numbers, the
      frequency of adverse drug reactions related to the prescribed application of HHS
      can be calculated: approximately 5 adverse drug reactions per 100,000 HHS units
      used; approximately 8-16 adverse drug reactions per 100,000 HHS-treated patients.
      CONCLUSION: Austrian experience with the use of a large number of HHS in clinical
      routine during nearly a decade indicates that the prescribed application of a
      combination of hydroxyethyl starch and hypertonic sodium chloride has a low
      potential for complications.

PMID- 12060976
TI  - Transplantation--how it all began.

PMID- 12060975
TI  - Anticoagulation with prostaglandins and unfractionated heparin during continuous
      venovenous haemofiltration: a randomized controlled trial.
AB  - BACKGROUND: The objective of this prospective, randomized, controlled clinical
      study was to compare efficacy, safety, and costs of fixed-dose prostaglandins
      with adjusted-dose unfractionated heparin as anticoagulants for continuous
      venovenous haemofiltration. PATIENTS AND METHODS: Perioperative critically ill
      patients requiring continuous haemofiltration for acute renal failure received
      unfractionated heparin anticoagulation titrated to achieve an activated clotting
      time in the extracorporeal system of > 120 s. Patients were randomly assigned to
      receive a test infusion containing either prostaglandin I2 (5 ng/kg/min; group I;
      n = 15; 75 filters), prostaglandin E1 (5 ng/kg/min; group E; n = 18; 72 filters),
      or placebo (group H; n = 17; 63 filters). Heparin and test solutions were infused
      into the extracorporeal circuit before the haemofilter. All AN69-surface hollow
      fiber filters were primed with normal saline containing 5.000 IU heparin.
      RESULTS: The primary outcome measure--adequate haemofilter life span > 24 h--was
      compared by using Cochran's Q test. There was a significant difference in the
      frequencies of adequate haemofilter life span between the groups (36% group H,
      65% group I, 59% group E; P < 0.05 versus group H). There were 6 bleeding
      episodes in group H, 2 in group E, and only 1 trivial bleeding episode in group I
      (P < 0.05 versus group H). Daily costs of haemofiltration were 61% higher in
      group I and 23% higher in group E than in group H (P < 0.05 versus group H). A
      heparin-sparing effect of prostaglandins was observed. CONCLUSIONS: Fixed-dose
      prostaglandins I2 and E1 reduced the incidence of haemofilter failure and
      bleeding when compared with adjusted-dose unfractionated heparin. There was no
      significant difference between the two prostaglandin groups. The increase in
      daily costs for haemofiltration treatment under prostaglandins is not clinically
      relevant.

PMID- 12060977
TI  - The beginning of organ transplantation: Emerich Ullmann (1861-1937).
AB  - Between 1880 and 1930 there was a rapid surge in experiments with tissue
      transplantation, initially mainly of endocrine tissues (thyroid, parathyroid,
      testicles, ovary, adrenals etc.) with the aim of replacing endocrine function.
      Emerich Ullmann (1861-1937), who was born in Pecs, Hungary and worked his whole
      life as a surgeon in Vienna was the first to perform transplantations of solid
      organs in the modern sense of medicine. During 1899 and 1900 he conducted several
      experiments with intestinal transplantation and must be regarded as the father of
      intestinal transplantation--a hitherto unknown fact. He then moved to kidney
      transplantation and on March 7, 1902 he demonstrated a dog with a functioning
      kidney graft anastomized to the collar vessels with urine dripping off the ureter
      sutured to the skin of the neck in the lecture hall of the Society of Physicians
      in Vienna. Ullmann was the first to perform kidney auto-, homo- and
      heterotransplantations and in 1902 also tried--unsuccessfully--to perform the
      first human kidney transplantation using a pig kidney which he anastomized into
      the cubital region of a women with end stage renal disease. Ullmann also
      performed tissue transplantations (skin, testicles, ovaries) and made other
      scientific discoveries and described several novel surgical techniques. Finally,
      in 1914 he wrote the first monograph on the state of the art of transplantation
      medicine, a booklet on "Tissue and Organ Transplantation" summarizing the
      surprisingly extensive experience in transplantation medicine of his time. With
      the obvious immunologic barriers to transplantation, the first "technical
      surgical period" of transplantation came to an end around the times of Ullmann's
      death and clinical transplantation was not to be revived before effective means
      of immunosuppression became available in the 1950s.

PMID- 12060978
TI  - Antioxidant therapy in glomerular disease.

PMID- 12060979
TI  - Curability of cancer in childhood and adolescence: acute lymphoblastic leukemia.

PMID- 12060980
TI  - Antioxidant treatment of therapy-resistant idiopathic membranous nephropathy with
      probucol: a pilot study.
AB  - BACKGROUND: Proteinuria in Heymann's nephritis, an experimental rat model disease
      corresponding to membranous nephropathy, has been shown to be due to lipid
      peroxidation. Since the pathophysiology might be similar to idiopathic membranous
      nephropathy in humans, we performed a prospective multicenter trial to
      investigate the efficacy of the lipid peroxidation scavenger, probucol. METHODS:
      Fifteen patients with biopsy-proven idiopathic membranous nephropathy resistant
      to conventional immunosuppressive therapy (n = 7) and/or ACEI treatment (n = 12)
      were recruited. Probucol (1 g/d orally) was administered for three months,
      followed by a washout period of four weeks, whereon lovastatin (10-20 mg/d
      orally) was administered for additional three months. RESULTS: A significant
      reduction in proteinuria was seen during the probucol treatment (median (range):
      6.4 (3.8-9.1) g/d vs. 4.7 (1.3-16) g/d; P < 0.05), with partial remission
      achieved in four patients. Three of these patients had previously been resistant
      to immunosuppressive therapy. Median protein excretion increased to pretreatment
      values during the washout period (6.2 (1.9-15) g/d; P < 0.05) and was not
      significantly different after the intake of lovastatin (4.9 (1.8-19) g/d; P =
      NS). None of the patients achieved partial remission during lovastatin therapy (P
      < 0.05 vs. probucol). CONCLUSION: The present study led us to conclude that
      proteinuria can be reduced by probucol in some patients with idiopathic
      membranous nephropathy. A randomized multicenter study to further elucidate the
      influence of lipid peroxidation scavengers on membranous nephropathy is
      warranted.

PMID- 12060981
TI  - Treatment results of childhood acute lymphoblastic leukemia in Austria--a report
      of 20 years' experience.
AB  - Between 1981 and 1999, 890 Austrian children with acute lymphoblastic leukemia
      (ALL) were treated in 5 consecutive trials using protocols from the Berlin
      Frankfurt-Munster (BFM) Group. In the trials BFM-A (Austria) 81 and ALL A 84,
      treatment stratification was performed using a risk factor, which was calculated
      from the initial peripheral blast cell count, and size of liver and spleen. In
      the following studies (BFM-A 86, 90 and 95) early response to a 7-day systemic
      mono-therapy with prednisone (as measured by the peripheral blast cell count) was
      used as an overriding stratification factor; in order to reduce the need for
      cranial radiotherapy, all patients received high-dose methotrexate (5 g/m2) for
      preventive central nervous system treatment. Event-free survival (EFS) rates
      increased from study BFM-A 81 (n = 141, probability (p) of EFS: 59% +/- 4%) and
      study ALL A 84 (n = 127, pEFS: 67% +/- 4%) to 77% +/- 4% in trial BFM-A 86 (n =
      142), 79% +/- 3% in trial BFM-A 90 (n = 256), and 84% +/- 3% in trial BFM-A 95 (n
      = 224). However, the prognosis for high-risk patients has not significantly
      improved within the last 20 years (pEFS: 50%). Furthermore, conventional risk
      factors such as leukocyte count and age at time of diagnosis, could not be used
      to indicate patients in the low and intermediate risk group who might eventually
      relapse. Thus, in trial BFM-A 2000, detection of minimal residual disease by
      polymerase chain reaction-based methods after 5 and 12 weeks of therapy was
      introduced for treatment stratification. Minimal residual disease was
      prospectively shown to predict relapses more precisely and, as a matter of fact,
      may allow a more exact definition of which patients are at risk and which
      patients belong to the subgroup with a good prognosis despite reduced treatment.

PMID- 12060982
TI  - Predictive role of laboratory and clinical treatment response parameters and
      glucose-6-phosphate dehydrogenase status in the therapy of falciparum malaria.
AB  - Beyond the criteria of success or failure, the treatment response in malaria may
      be characterized by a number of clinical parameters such as fever and parasite
      clearance. These factors are influenced by various biochemical and haematological
      factors and the parasite's drug response. The aim of the study was the
      determination of the value of treatment response parameters and their relation to
      laboratory findings in the treatment of falciparum malaria, irrespective of the
      severity of disease and the treatment used. The study was conducted at the
      Hospital for Tropical Diseases in Bangkok with 119 inpatients suffering from
      falciparum malaria. The median fever (FCT), parasite (PCT) and symptom (SCT)
      clearance times were 29.75, 43.00 and 48.00 hours respectively. Fever clearance
      was found to be closely associated with the other two response parameters as well
      as with the parasite count on admission (P < 0.001), which was therefore found to
      be a good predictor for the expected duration of the clinical disease. Another
      important predictor for the persistence of fever may be the glucose-6-phosphate
      dehydrogenase (G6PD) status of the patients. Individuals with normal G6PD-values
      had almost double the FCT as compared to those with G6PD-deficiencies (46.5
      versus 27.2 hrs), an indication of a protective role conferred by low G6PD
      levels. A positive association between red blood cell count and FCT (P = 0.009),
      may be attributed to a similar protection mediated by anaemia. A possible
      explanation could lie in the high frequency of haemoglobinopathies in Southeast
      Asia and their relation to malaria. No comparable associations were noted for PCT
      and SCT. Particularly the fever clearance was therefore found to be a good
      indicator of treatment response. Several parasitological and haematological
      parameters, such as G6PD level and parasitaemia, were identified as reliable
      predictors of the expected duration of clinical disease in malaria.

PMID- 12060984
TI  - C-quence: a tool for analyzing qualitative sequential data.
AB  - C-quence is a software application that matches sequential patterns of
      qualitative data specified by the user and calculates the rate of occurrence of
      these patterns in a data set. Although it was designed to facilitate analyses of
      face-to-face interaction, it is applicable to any data set involving categorical
      data and sequential information. C-quence queries are constructed using a
      graphical user interface. The program does not limit the complexity of the
      sequential patterns specified by the user.

PMID- 12060983
TI  - Voice recognition technology as a tool for behavioral research.
AB  - Behavioral research often requires the acquisition and processing of large
      volumes of data. Most current techniques for recording behavior constrain the
      amount and type of data that can be measured. We developed and tested a system
      that uses voice recognition technology to collect data on the social interactions
      and singing patterns of cowbirds (Molothrus ater) living outdoors in a semi
      natural environment. We spoke observation data into a wireless microphone that
      transmitted the data to a computer in the laboratory. After collection, the data
      were automatically checked for errors and then were entered into a database.
      Overall, the system performed at extremely high levels of accuracy. Furthermore,
      owing to the removal of constraints on observers such as breaking visual contact
      with subjects and manual data entry into a database, we were able to increase the
      amount of data collected and to collect new measures of social interactions that
      have not been available to us in the past. We tested the system under the
      challenging circumstances of field observation, and it performed above our
      expectations. In a laboratory setting, if transmission difficulties are removed,
      voice recognition could be even more accurate. We recommend voice recognition as
      a powerful new tool for the variety of research fields in which measuring
      behavior is involved.

PMID- 12060985
TI  - Fractional Design Wizard: a computer program for cost-effective experimental
      research design.
AB  - The computer program Fractional Design Wizard creates fractional factorial
      designs that are cost-effective and especially useful for discarding irrelevant
      factors from a large number of possible candidates. The program is intended for
      researchers who are relatively new to the field of fractional design and who want
      to acquaint themselves with the use of fractions for the reduction of large
      experimental designs. Fractional designs allow estimation of main effects, and
      sometimes two-way interactions, without one's having to examine all treatment
      conditions. The program needs Microsoft Windows 95 or better and 32 MB of memory.
      In a step-by-step fashion, the user can specify the required properties of the
      fractional design. When there are more valid designs, the user can generate these
      successively. If necessary, the user can go back to diminish the requirements.
      The output can be copied, printed, and saved. The program generates all the
      information that is needed for the use and interpretation of fractional designs.
      A help file explains the use of the program and also the purpose, the analysis,
      and the interpretation of fractional designs. The program, which is written in
      Object Pascal, is available as freeware on www.fss.uu.nl/ms/hl/fracdes.htm.

PMID- 12060986
TI  - Completion norms for 112 Spanish sentences.
AB  - Sentence completion norms are a valuable resource for researchers interested in
      studying the effects of context on word recognition processes. Norms for 112
      Spanish sentences were compiled with the use of experimental software accessed
      over the World-Wide Web. Several measures summarizing the distribution of
      responses for each sentence are reported, including Schwanenflugel's (1986)
      multiple-production measure of sentence constraint strength, the type-token
      ratio, and the information-theoretic measure of redundancy. The complete set of
      completion norms is available at
      http://www.ling.ed.ac.uk/~monica/spanish_completion_norms.html.

PMID- 12060987
TI  - Cognitive modeling with spreadsheets.
AB  - Spreadsheet implementations of two different types of cognitive models--a neural
      network model and a statistical model--are presented. The two examples illustrate
      how to employ the facilities of spreadsheets, the spreadsheet data structure,
      array functions, the built-in function library, and the integrated optimizer, for
      building cognitive models. The two presented models are new extensions of
      existing models. They are used for simulating data from experiments illustrating
      that the extended versions are able to explain experimental results that could
      not be simulated by the original models. The whole simulation study demonstrates
      that spreadsheets are a handy tool, especially for researchers without
      programming knowledge who want to build cognitive models and for instructors
      teaching cognitive modeling.

PMID- 12060988
TI  - Variance of d' for the same-different method.
AB  - Variance estimates of d' are derived toward the same-different method based on
      Taylor-series expansion with one and two variables. The variance estimates can be
      used for statistical comparison of d's obtained from various discrimination
      paradigms. Formulas and tables for estimating variance of d' for the method are
      provided. One S-PLUS program, which can produce both d' and variance of d', is
      also provided.

PMID- 12060989
TI  - Response rate, speed, and completeness: a comparison of Internet-based and mail
      surveys.
AB  - Because of their speed and accessibility, the use of on-line research tools has
      grown considerably in recent years. The present study compared two ways of
      delivering surveys: Internet-based and mail delivery methods. Although Internet
      based and mail surveys achieved a similar response rate, Internet-based surveys
      may be more effective than mail surveys in a setting such as when the target
      population has both e-mail and Internet access.

PMID- 12060990
TI  - A comparison of World-Wide Web and paper-and-pencil personality questionnaires.
AB  - Does the manifestation of response set effects in World-Wide Web (WWW)
      questionnaire responses differ from that in paper-and-pencil (PP) questionnaire
      responses? Two thousand six hundred and forty-nine volunteers responded to a WWW
      questionnaire, and 458 volunteers responded to a PP questionnaire consisting of
      five personality scales. Five response sets were examined. For four of them-
      random response, item nonresponse, extreme response, and acquiescent response--no
      statistically significant differences between PP and WWW data were found. The PP
      administration elicited a statistically higher number of errors (uncodable
      responses), although eta 2 was less than .02. An analysis of interitem and
      interscale correlations did not differentiate WWW and PP data. Data from the
      Marlowe-Crowne Social Desirability Scale, the Perfectionist Self-Presentation
      Scale, and the Computer Anxiety Scale did not differentiate WWW and PP data in
      terms of either means or scale reliabilities. It was concluded that WWW data may
      be comparable to PP data and that the WWW is a potentially useful and valid data
      collection tool.

PMID- 12060991
TI  - Using Matlab to generate families of similar Attneave shapes.
AB  - We present a program for Matlab that quickly generates Attneave-style random
      polygons and families of similar polygons. The function allows a great deal of
      user control over various aspects of the shape generation process. It also has
      the ability to detect and eliminate shapes that do not match a variety of user
      entered parameters regarding the lengths of the shapes' sides, vertex angles, and
      topological form. The function eliminates the time-consuming task of generating
      such shapes by hand and should allow their broader use in behavioral research.
      The Matlab script function can be downloaded at
      www.dal.ca/~mcmullen/downloads.html.

PMID- 12060992
TI  - Quantification of brain lesions using interactive automated software.
AB  - We developed an interactive program, Analysis of Brain Lesions (ABLe) so that
      researchers studying the effects of brain lesions on cognition could have a user
      friendly tool that could quantitatively characterize such lesions. The program
      was prepared in Tcl/Tk and will run on any UNIX or PC LINUX platform with the
      MEDx medical imaging software package. The ABLe is almost completely automated
      and determines the brain lesion size as well as which cytoarchitectonic brain
      regions (Brodmann areas) are contained within the boundaries of the lesion.
      Lesion data from multiple subjects can be grouped together and the degree of
      lesion overlap displayed. All images are analyzed and displayed within standard
      Talairach coordinate space, and the precision of the match between the ABLe
      Brodmann area graphics and the subject/patient brain is easily confirmed. The
      program is the first easy-to-use software that contains these specific features
      and is available for interested researchers with a background in lesion analysis.

PMID- 12060993
TI  - A jigsaw-puzzle imagery task for assessing active visuospatial processes in old
      and young people.
AB  - Recent studies have suggested a theoretical distinction between active
      elaboration and passive storage in visuospatial working memory, but research with
      older adults has failed to demonstrate a differential preservation of these two
      abilities. The results are controversial, and the investigation of the active
      component has been inhibited by the absence of any appropriate experimental
      procedures. A new task was developed involving the mental reconstruction of
      pictures of objects from fragmented pieces, and this provides a useful procedure
      for exploring active visuospatial processing. Significant differences in terms of
      both correctness and response latency were obtained between young and older
      adults and between younger old and older old adults. Performance also varied with
      visual complexity, mental rotation, and processing load. It is concluded that
      this ecologically relevant procedure constitutes a very powerful, sensitive, and
      reliable tool for identifying individual differences in visuospatial working
      memory.

PMID- 12060994
TI  - Mimics: a symbolic conflict/cooperation simulation program, with embedded
      protocol recording and automatic psychometric assessment.
AB  - This paper describes an interactive software environment designed as a social
      interaction simulator with embedded comprehensive recording and flexible
      assessment facilities. Using schematized visual sketches similar to cross
      cultural facial universals (Ekman, 1999), Mimics (Shmelyov & Aidman, 1997)
      employs a computer-game-like scenario that requires the subject to identify with
      an avatar and navigate it through a playing field inhabited by hosts who display
      a range of facial expressions. From these expressions (which are highly
      consequential), the player has to anticipate the hosts' reactions to the avatar
      (which may vary from friendly to obstructing or aggressive) and choose between
      negotiating with a host (by altering the avatar's facial expression), attacking
      it, or searching for an escape route. Comprehensive recording of player moves and
      interactions has enabled computation of several finegrained indices of
      interactive behavior, such as aggressive response styles, efficiency, and
      motivation in conflict/cooperation contexts. Initial validation data and
      potential applications of the method in the assessment of personality and social
      behavior are discussed.

PMID- 12060995
TI  - A Macintosh and Windows program for assessing body-image disturbance using
      adjustable image distortion.
AB  - Body image is one of the most important concepts in the study of eating
      disorders. The assessment and treatment of body-image issues are considered to be
      integral aspects of assessment and clinical management of eating disorders
      (Thompson, 1996b). The program, BodyImage, is software for the assessment of body
      image disturbance. It uses an image-distorting technique to estimate body size.
      The image of the whole body or parts of the body can be captured as a digital
      image by a digital camera. Response data from participants are recorded as ASCII
      files so that other computer programs such as spreadsheets or word processing
      programs can handle the data. BodyImage works on personal computers, both
      Macintosh and Windows. It is available at no cost, and it can be obtained from
      the following URL: http://homepage2.nifty.com/s_shibata/softwares/bodyimage.html.

PMID- 12060996
TI  - ETAT: Expository Text Analysis Tool.
AB  - Qualitative methods that analyze the coherence of expository texts not only are
      time consuming, but also present challenges in collecting data on coding
      reliability. We describe software that analyzes expository texts more rapidly and
      produces a notable level of objectivity. ETAT (Expository Text Analysis Tool)
      analyzes the coherence of expository texts. ETAT adopts a symbolic
      representational system, known as conceptual graph structures. ETAT follows three
      steps: segmentation of a text into nodes, classification of the unidentified
      nodes, and linking the nodes with relational arcs. ETAT automatically constructs
      a graph in the form of nodes and their interrelationships, along with various
      attendant statistics and information about noninterrelated, isolated nodes. ETAT
      was developed in Java, so it is compatible with virtually all computer systems.

PMID- 12060997
TI  - Dissecting the genetic component of complex diseases in humans.

PMID- 12060998
TI  - Statistical methods for analyzing gene expression data for cancer research.

PMID- 12060999
TI  - Comparing secondary structure 'stick' models of proteins using graph matching
      with double dynamic programming.

PMID- 12061000
TI  - Computational structural proteomics.

PMID- 12061001
TI  - Proteomics in biological research: the challenge to make proteins speak.

PMID- 12061002
TI  - Bioinformatics of membrane proteins.

PMID- 12061003
TI  - Construction and prediction of protein-protein interaction maps.

PMID- 12061004
TI  - Bioinformatics, cellular flows, and calculation.

PMID- 12061005
TI  - Graph-based analysis of metabolic networks.

PMID- 12061006
TI  - Orphan protein function and its relation to glycosylation.

PMID- 12061007
TI  - Promoter analysis.

PMID- 12061008
TI  - Cluster analysis and its applications to gene expression data.

PMID- 12061009
TI  - Bioinformatics and genome analysis. Preface.

PMID- 12061010
TI  - The future of dentistry: today's vision, tomorrow's reality. Vision and
      recommendations.

PMID- 12061011
TI  - Mobility, testing among future licensure issues and regulations.

PMID- 12061012
TI  - Oral health care knows no borders.

PMID- 12061013
TI  - Government involvement does not improve access to dental services.

PMID- 12061014
TI  - "Dental" care will evolve into "patient" care.

PMID- 12061015
TI  - Dental education will continue to face extreme challenges.

PMID- 12061016
TI  - Dental education: the cost of doing business.

PMID- 12061018
TI  - Reflections on the purpose, visions, and recommendations of the American Dental
      Association Future of Dentistry report.

PMID- 12061017
TI  - Microleakage of high-strength glass ionomer: resin composite restorations in
      minimally invasive treatment.
AB  - Atraumatic Restorative Treatment (ART) has been investigated as an alternative
      caries treatment. The technique involves removal of loose tooth structure with a
      spoon excavator, followed by placement of an adhesive restorative material, often
      a high-strength glass ionomer. This study compares the microleakage of a high
      strength glass ionomer/resin composite and two occlusal resin composite
      restoration techniques.

PMID- 12061019
TI  - The influence of the Future of Dentistry report on state dental societies.

PMID- 12061020
TI  - The occurrence of malignant carcinoid syndrome in patients with carcinoid tumors.
AB  - BACKGROUND: The carcinoid syndrome occurs in about 10% of patients with carcinoid
      tumors. OBJECTIVES: The main objective of the present study was to determine the
      presence of the carcinoid syndrome in a group of patients with carcinoid tumor.
      SUBJECTS AND METHODS: 35 pts with carcinoid tumors (group A--24 pts with
      metastatic disease, group B--11 pts after resection of the primary tumor with no
      metastases detected at the time of the investigation) were included into the
      study. The localisation and the diameter of the primary tumor were ascertained.
      Somatostatin receptor scintigraphy--Octreoscan and echocardiography were done.
      The urinary excretion of 5-HIAA was performed. We estimated the presence of the
      carcinoid syndrome in all patients. RESULTS: We confirmed the difference in the
      diameter of the primary carcinoid tumor in patients with metastases--group A 3.0
      (2.5-4.2) cm by comparison with group B 0.7 (0.6-0.8) cm, (p < 0.001). Patients
      in the metastatic group are older 64 year (42-70) than pts without metastases--33
      y (20-54) (p < 0.01). The amount of the 5-hydroxyindolacetate acid in urine in
      pts with metastatic carcinoid was statistically significantly higher than in the
      pts without metastases (p < 0.001). The carcinoid syndrome in the metastatic
      group was found in 6 patients (25%), with maximum (12.5%) localised in midgut.
      Out of the whole sample it counts up to 15.1%. During the follow up period, 8
      patients from group A died. CONCLUSION: The large diameter of the primary
      carcinoid tumor and the higher age are the bad prognostic factors in patients
      with carcinoid tumors. (Tab. 4, Ref. 27.)

PMID- 12061022
TI  - The effect of cardiovascular autonomic neuropathy on resting ECG in type 1
      diabetic patients.
AB  - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of
      diabetes mellitus. AIM: To assess the manifestations of CAN on ECG at rest.
      SUBJECTS AND METHODS: 100 type I diabetic patients, mean age 36.5 (range 17-62)
      years, mean duration of diabetes 14.6 (range 0-49) years were examined. The
      control group consisted of 88 healthy subjects, mean age 37 (range 15-65) years.
      Cardiovascular reflexes (respiration sinus arrhythmia, orthostatic test and
      Valsalva's maneuvre) were examined, and ECG at rest was analysed. RESULTS: In 35
      (35%) diabetics CAN was established. In comparison to diabetic patients without
      neuropathy, patients with CAN had a higher heart rate (94, 89-99 vs. 79, 75-82
      heart beats.min-1, p < 0.001), higher P wave voltage (0.13, 0.12-0.15 vs 0.11,
      0.09-0.12 mV, p < 0.001), as well as QTc interval length (422, 410-433 vs 396,
      388-404 ms, p < 0.001), but they had a lower voltage of R wave (0.83, 0.72-0.94
      vs. 1.0, 0.91-1.09 mV, p < 0.05) and lower T wave voltage (0.18, 0.15-0.21 vs
      0.23, 0.19-0.27 mV, p < 0.05). CONCLUSIONS: The higher voltage of P wave, lower
      voltage of T wave, shorter PQ interval and prolonged QTc interval with
      tachycardia may be the manifestation of relative sympatheticotonia. Lower R wave
      voltage and the prolonged QRS complex are the possible signs of cardiomyopathy.
      (Tab. 4, Ref. 31.)

PMID- 12061021
TI  - Comparison of vasoconstrictor responses to selected NSAIDs in rabbit renal and
      femoral arteries.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to
      induce adverse renal effects, which are closely related to physiological
      inhibition of renal prostaglandin synthesis. AIM: This study was aimed to
      evaluate the effect of drugs inhibiting both cyclooxygenase (COX) isoforms COX-1
      and COX-2 on vasoconstrictor responses to noradrenaline in the rabbit renal
      artery and to compare these responses with femoral artery as a systemic vessel.
      METHODS: Rabbit femoral and renal arteries were perfused with a constant flow.
      Vascular responses to drugs were measured and registered as changes in perfusion
      pressure. RESULTS: It was found that the vasoconstrictor responses to
      noradrenaline were significantly enhanced after administration of all NSAIDs in
      both the renal and femoral arteries. The effect of indomethacin on renal
      vasoconstrictor responses was more pronounced compared to ibuprofen or
      phenacetin. Comparison of NSAIDs effects on renal and femoral arteries did not
      show significant differences. CONCLUSIONS: These results demonstrate an increase
      of vasoconstrictor activity after NSAIDs administration without significant
      differences between the renal and femoral arteries. The strongest potentiation of
      the vasoconstrictor responses in the renal artery was found with indomethacin.
      (Tab. 1, Fig. 4, Ref. 20.)

PMID- 12061023
TI  - The circalunar cycle of salivary testosterone and the visual-spatial performance.
AB  - BACKGROUND: A circalunar cycle is thought to be female sex specific. Results of
      studies observing the relationship of testosterone and spatial abilities are
      controversial. OBJECTIVE: To describe the infradian variations of testosterone
      and the correlations between salivary testosterone levels and spatial abilities
      in young healthy volunteers of both sexes. SUBJECTS AND METHODS: Testosterone
      levels in saliva were determined in 53 young adult male and female subjects (mean
      age--20.89 +/- 0.91 years). The samples of saliva were collected either once (22
      subjects) or daily during a period of 30 days (31 subjects). Salivary
      testosterone was analyzed by RIA. Both groups of subjects were tested on their
      visual-spatial performance (mental rotation and spatial visualization). All
      important data about the menstrual cycle of female subjects were also collected.
      This data and the results of the visual-spatial tests as well as the circalunar
      cycle in their relationship to the testosterone levels were analyzed. RESULTS: In
      this study a circalunar rhythm of testosterone related to the menstrual cycle
      with a maximum peak in the periovulatory phase was confirmed in women and an
      analogical circalunar cycle in men was described. A positive correlation of the
      salivary testosterone levels and the performance in visual-spatial tests in women
      and a negative dependence in men was found. The outcomes showed a significant
      statistical difference between the results of the test during the high
      testosterone and the low-testosterone phase in both sexes. CONCLUSIONS: The
      levels of testosterone between the high female and low male range seem to be
      associated with the best spatial ability performance in adults. A male circalunar
      rhythm similar to the female one is very likely. Recognizing of the infradian
      fluctuations in women as in men should have many various clinical implications.
      (Tab. 2, Fig. 7, Ref. 143.)

PMID- 12061024
TI  - Serum markers of liver fibrogenesis, and liver histology findings in patients
      with chronic liver diseases.
AB  - AIM OF THE STUDY: Investigation of the relationships between the grade and stage
      of chronic liver diseases irrespective of their etiology using some novel serum
      markers of liver fibrogenesis, the "classical" serum markers of liver necro
      inflammatory injury (such as transaminases), and the histomorphological
      evaluation of liver biopsies. METHODS: Markers of liver fibrogenesis: serum
      metalloproteinase 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-1), and N-terminal
      propeptide of the procollagen III (PIIINP); "liver function tests" (LFTs):
      bilirubin, transaminases ALT, AST; ALP, GMT; and liver morphology findings: necro
      inflammatory activity, fibrosis; were studied in the series of 32, 'naive', i.e.
      yet untreated patients (women/men--11/21) with various CLDs: chronic viral
      hepatitis B or C 13 (CHB 3, CHC 10), non-alcoholic steatohepatitis 9, liver
      steatosis 4, primary biliary cirrhosis 5, drug-induced hepatitis. The diagnoses
      were based on the clinical, laboratory and liver imaging (ultrasonography)
      findings and confirmed by the liver biopsy. CONCLUSIONS: Investigation of liver
      fibrogenesis serum markers (PIIINP, MMP-1, TIMP-1) in patients with various CLDs
      has shown statistically significant correlations of these parameters with
      "classical" serum markers of liver necro-inflammation (ALT, AST) and the results
      of histomorphological evaluation of the necro-inflammatory activity (parameters
      NAI, MEF) and fibrosis (parameter FI) in liver biopsies. (Tab. 4, Ref. 31.)

PMID- 12061025
TI  - Hepatic fibrogenesis.
AB  - The main pathogenic mechanism of the progress of chronic hepatitis into cirrhosis
      is represented by fibrogenesis. Stopping this progress is the subject of much
      research and would. The hepatic stellate cells play a central role based on their
      ability to undergo activation following liver injury from any cause is important.
      On the basis of improved knowledge of the pathophysiology of fibrogenesis, the
      development of new therapeutic approaches will become possible. (Fig. 3, Ref.
      50.)

PMID- 12061026
TI  - The pedagogical aspects in the physical measurements provided in medicine.
AB  - Nowadays, the graduates of medical faculties should be able to use up to date
      complicated technical devices as well as various diagnostic and therapeutic
      methods based on physical laws and processes. Therefore good knowledge in physics
      (including some fields of modern physics) is expected to be mastered by students
      during their studies of physics at the faculty. The shortness of time that is
      available for the teaching of physics has forced us to the laboratory exercises
      to the maximum extent. In this contribution, some special measurements will be
      described. The authors also discuss the possibilities of applying new practical
      and theoretical approaches, and stress the significance of the teaching of
      applied physics at medical faculties for the quality of medical care in the
      future. (Ref. 18.)

PMID- 12061027
TI  - Niels Stensen--prestigious scholar of the 17th century.
AB  - The authors present a biography of modest, extraordinary educated Danish scholar
      Niels Stensen, who gave his life to anatomy, geology and finally to theology. His
      anatomical studies of salivary glands, lymphatic system, muscles and heart, and
      also of other organs of human body, based on study of contemporary anatomy
      classify him among most important scholar of 17th century. The truth, scientific
      approach and his method of explaining anatomical structures in a connection with
      physiological notes are original and valid from a todays point of view. (Fig. 3.
      Ref. 8.)

PMID- 12061029
TI  - Elimination of lymphatic filariasis.

PMID- 12061028
TI  - Retrobulbar neuritis associated with Borrelia afzelii infection.
AB  - PURPOSE: To report retrobulbar neuritis caused by Borrelia afzelii culturally
      proved from cerebrospinal fluid (CSF). METHODS: A 23 year old female underwent
      ophthalmologic, laboratory and other auxilliary examinations. RESULTS: CSF
      cultures grew spirochetal microorganisms, serotyped by monoclonal antibodies as
      Borrelia afzelii. Following the serological and cultural results, treatment with
      doxycycline 200 mg daily was started and kept for three weeks. Gradual
      improvement of the visual acuity of the right eye was observed with full recovery
      to 20/20. CONCLUSIONS: Borrelia infection should be considered in the
      differential diagnosis of retrobulbar neuritis. CSF should be examined also
      culturally. (Ref. 5.)

PMID- 12061030
TI  - Global agenda on influenza--adopted version. Part I.

PMID- 12061031
TI  - Psychosomatics and reproductive medicine: a good relationship?

PMID- 12061032
TI  - Medical students' opinions of chaperone use during gynecological and anorectal
      examinations.
AB  - The opinions of medical students on chaperone use during physical examinations of
      the male and female was studied. The students (157) had conducted their first
      gynecological or first anorectal and prostate examination. Fifty-one percent of
      students were female, 56% younger than 25 years of age, and 77% males and 73%
      females had experienced sexual intercourse. Data on the use of a chaperone during
      vaginal, anorectal, breast and musculoskeletal examinations when conducted by
      doctors and by students was collected by anonymous questionnaires. Most students
      feel a chaperone is necessary when students-in-training conduct vaginal (94%),
      anorectal (94%) or breast (89%) examinations. Fewer students feel a chaperone is
      necessary when doctors rather than students conduct vaginal (41%), anorectal
      (22%) and breast (25%) examinations. Students were significantly more likely to
      feel a chaperone was necessary when a doctor of the opposite sex conducts vaginal
      (58%) and anorectal (34%) examinations, compared to a doctor of the same sex.
      Students who were male, 25 years or older or had not experienced sexual
      intercourse were significantly more likely to favour doctors using chaperones.
      The differences in responses of students of differing age, gender and sexual
      experience should be considered and discussed when students are learning invasive
      physical examinations.

PMID- 12061033
TI  - Women's experiences of pelvic examination: an interview study.
AB  - This qualitative study was designed to explore women's experiences when
      undergoing pelvic examination (PE). Earlier studies have shown that women are
      positive to the PE in general, but when describing the specific parts of the
      procedure, negative terms are used, for example, fear, pain, feelings of
      humiliation and embarrassment. Data were collected by tape-recorded narrative
      interviews, with six women aged 20-41 years, who had undergone several PE. A
      qualitative content analysis was used and three main themes were revealed: the
      experience of being exposed, the experience of having a trusting relationship
      with the examiner and the experience of a comforting environment. The findings
      revealed that it was not only the PE that affected the women, but also the
      relationship to the examiner. The experience of being exposed could be decreased
      by, for example, separating the body from the person, being able to relax and by
      having a trusting relationship with the examiner. The women appreciated having a
      homelike environment in the outpatient clinic. If women are met and confirmed in
      accordance with these findings, the examination may be an event without negative
      experiences for them.

PMID- 12061034
TI  - Major depression in unexplained infertility.
AB  - Although a potential relationship between depression and infertility has been
      described throughout history, only recently has this topic been subjected to
      systematic investigation, and the literature is often confusing. The present
      study uses well-established structured psychiatric interviews--Structured
      Clinical Interview for DSM-III-R (SCID), Beck and Family History-Research
      Diagnostic Criteria (Fh-RDC)--to investigate the prevalence of major depression
      in a small group of women with infertility of unknown origin, and a community
      control sample. There were significantly more women with current depression or a
      history of depression in the infertile group, and of these women the majority
      experienced their first depressive episode prior to their diagnosis of
      infertility.

PMID- 12061035
TI  - Traumatic stress after childbirth: the role of obstetric variables.
AB  - In a sample of 1550 recently delivered women, traumatic stress after childbirth
      was studied in relation to obstetric variables. A post-traumatic stress disorder
      (PTSD) symptom profile and traumatic stress symptoms were assessed by means of
      the Traumatic Event Scale (TES). Obstetric data comprised delivery mode, duration
      of the second stage of labor (the time from cervical dilation of 10 cm to partus)
      and the use of analgesia/anesthesia. Traumatic stress symptoms and having a PTSD
      symptom profile were both significantly related to the experience of an emergency
      cesarean section or an instrumental vaginal delivery. It is of clinical
      importance, however, that most women with a PTSD symptom profile were found in
      the normal vaginal delivery group (NVD). This implies that a normal vaginal
      delivery can be experienced as traumatic, just as an emergency cesarian section
      is not necessarily traumatic. Traumatic stress symptoms were neither
      substantially correlated to the duration of the second stage of labor, nor to the
      use of analgesia/anesthesia.

PMID- 12061036
TI  - Survey of psychological health in women with infertility.
AB  - The aims of this study were to assess mental well-being in women undergoing
      investigation and initial management of infertility and to determine any specific
      factors, such as the duration or type of infertility, that might be associated
      with an increased risk of psychological morbidity. A postal survey was sent to
      1080 women with infertility attending gynecology outpatient departments in 12
      Scottish centres. The survey included the Twelve-Item General Health
      Questionnaire (GHQ-12) and three multi-item scales from the Short Form Health
      Survey Questionnaire (SF-36). The response rate was 47.4% (512/1080) of which 507
      completed the GHQ-12. Of the 507 GHQ-12 responders, 32.5% had a GHQ-12 score of >
      or = 8/12 suggesting they were at risk of clinically significant psychological
      disturbance. There were no significant associations between GHQ-12 scores and
      duration of infertility, the presence of existing children, or the cause of
      infertility. GHQ-12 scores significantly increased with the number of clinic
      attendances and decreased as the patient's age increased. Responders scored
      significantly lower on all aspects of the selected SF-36 questions as compared to
      published population data, suggesting poorer mental health. These standardized
      psychological instruments suggest that approximately 32% of women in the early
      stages of infertility management may be at risk of developing clinically relevant
      mental health problems. Psychological aspects of infertility should be addressed
      as part of a more holistic approach to management of these patients.

PMID- 12061037
TI  - Vulvar vestibulitis syndrome: care made to measure.

PMID- 12061039
TI  - Be fruitful and multiply: assisted reproduction and cloning.

PMID- 12061038
TI  - Women's sexual behavior, body image and satisfaction with surgical outcomes after
      hysterectomy: a comparison of vaginal and abdominal surgery.
AB  - The aim of this study was to investigate the impact of vaginal and abdominal
      hysterectomy on women's sexual behavior, sexual dysfunction, body image and
      satisfaction with surgery. A prospective study was conducted on 90 women to
      evaluate the outcomes of hysterectomy. Data were collected prior to surgery,
      three months and two years after surgery, using self-report questionnaires. The
      results showed significant differences in women's sexual behavior and sexual
      dysfunction before and after hysterectomy, independent of the surgical procedure
      performed. Women in both groups reported improvements in sexual desire, sexual
      activity and sexual intercourse three months and two years after surgery. Sexual
      dysfunction such as dyspareunia, vaginismus, lack of orgasm and loss of sexual
      interest diminished significantly after surgery. Regression analyses revealed
      that postmenopausal status, severity of gynecological complaints and frequency of
      sexual intercourse were the most important factors for improved sexual outcomes.
      Women in the abdominal group were dissatisfied with their body image because of
      the abdominal scar, experienced more pain and had a longer period of recovery
      from surgery compared to women in the vaginal group. According to the results,
      sexual behavior alone is not an important factor in choosing vaginal or abdominal
      hysterectomy. However, sexual behavior was important in both groups when
      evaluating outcomes after hysterectomy.

PMID- 12061040
TI  - Guidelines are systematically developed descriptions and recommendations on
      prevention, diagnostics, therapy and after-care for patients under specific
      circumstances.

PMID- 12061044
TI  - Boutique health care: opportunity or inequity?

PMID- 12061041
TI  - In favor of an integrated pain-relief treatment approach for vulvar vestibulitis
      syndrome.

PMID- 12061045
TI  - Speranzo: ensuring large health system accountability in the wake of Enron.

PMID- 12061046
TI  - Internet-based search tools can help reduce bad debt.
AB  - The healthcare industry wrote off more than $20 billion in bad debt in 1999
      alone, according to one estimate. Bills frequently do not reach patients because
      healthcare organizations do not have accurate patient contact and billing
      information. Incorrect billing information can be easily and inexpensively
      corrected by using Internet-based search tools. Healthcare accounts receivable
      staffs are using these tools to improve the patient experience and the bottom
      line with no capital outlay, minimal staff training or workflow change
      requirements, and low cost.

PMID- 12061047
TI  - Improving managed care value through customer service.
AB  - The ability of managed care providers to deliver high-quality customer service to
      managed care customers depends on their adoption of basic customer-service
      principles. To apply these principles effectively, providers need to understand
      and work to exceed the particular needs and expectations of these customers,
      which include boards of directors, senior executives, physicians, healthcare
      providers, clinical and patient financial services managers and staff, employers,
      brokers, and patients. Although these needs and expectations can be predicted to
      some extent, providers would be wise to implement regular surveys of customers
      and an open procedure for soliciting customer feedback about service issues.
      Better customer service for the broad range of managed care customers translates
      into higher levels of employer and patient satisfaction, which ultimately
      benefits providers.

PMID- 12061048
TI  - A commitment to the profession.

PMID- 12061049
TI  - Winning employee-retention strategies for today's healthcare organizations.
AB  - Employees today want more out of a job than a big salary. Workers' expectations
      have shifted over the past few decades. Employers need to recognize five key
      changes in workers' expectations, namely that they want to lead balanced lives,
      enjoy partnership with their employers, receive opportunities for personal and
      professional growth, be able to make a meaningful contribution to the world
      through their work, and experience opportunities to socialize at work. Healthcare
      organizations that want to attract and retain the employees that they need can
      achieve competitive advantage in the marketplace by responding to these new work
      values.

PMID- 12061050
TI  - Raising the bar on recruitment and retention.
AB  - Although finding and keeping talented staff is a problem that affects virtually
      every healthcare organization, Falls Church, Virginia-based Inova Health System
      found itself particularly challenged by a fiercely competitive market and failing
      employee retention system. Large percentages of staff in Inova's finance division
      were employed for less than one year. To address this staffing crisis, department
      leadership joined with human resource representatives and employees to pursue a
      practical strategy emphasizing self-analysis, responsive solutions, and promotion
      of recruitment activities. In less than a year, the division had exceeded its
      expectations--vacancies were significantly reduced, use of temporary replacements
      had ceased, and members of the public were recognizing the organization as an
      industry leader.

PMID- 12061051
TI  - Using Internet technology to streamline healthcare recruiting.
AB  - The staffing shortages currently facing healthcare organizations may become more
      severe in the future. Using the Internet to facilitate the process of
      identifying, interviewing, and hiring candidates for healthcare positions can
      result in cost-effective, appropriate hiring decisions and reduce the amount of
      time human resources personnel must spend performing administrative tasks
      relating to hiring. In addition, this technology contributes to improved
      satisfaction of current employees by identifying those who are most eligible for
      promotion.

PMID- 12061052
TI  - Assessing the impact of Medicare payment changes.
AB  - A reduction in the conversion factor applied to Medicare's payment equation has
      many providers concerned about financial loss. Some of this concern is justified,
      as most practices will see a decline in revenue that could result in a similar
      decline in physician compensation. However, the impact of these payment changes
      may be offset somewhat by increases in the relative value units assigned to many
      commonly performed procedures. Providers also can take several operational steps
      to minimize effects on their bottom lines.

PMID- 12061053
TI  - Use of electronic signatures: past and present.

PMID- 12061054
TI  - Data trends. Broadening the use of financial data to improve patient care.

PMID- 12061055
TI  - Evaluating the organizational effectiveness of APC implementation efforts.
AB  - To optimize revenue under the Medicare outpatient prospective payment system's
      new coding-based ambulatory payment classifications (APCs), healthcare providers
      need to ensure several key steps are taken at the organizational level.
      Individuals who manage coding need to identify areas of overlap and adjust
      billing systems to reflect changes under the system. Billing managers should
      develop practices and protocols that provide detailed reviews of claims,
      implement a formal denial management program, track reasons for denials, and
      communicate denial information with their staffs. Proper evaluation of financial
      practices also is important. Financial managers need to develop formal ways to
      monitor financial performance consistently and on an ongoing basis and ensure the
      hospital is generating sufficient volume and keeping service costs in line with
      payments.

PMID- 12061056
TI  - Washington state: a laboratory for healthcare policy.

PMID- 12061057
TI  - Edentulism and its potential implications.

PMID- 12061058
TI  - Posterior considerations.

PMID- 12061059
TI  - The perio-aesthetic-restorative approach for anterior reconstruction--Part I:
      Evaluation and periodontal surgery.
AB  - Precise communication is critical to the delivery of functional and aesthetic
      restorations. Interdisciplinary therapy integrates individual disciplines to
      function as a comprehensive unit and consistently provide predictable treatment
      results. Thorough diagnosis and treatment planning must be executed between every
      member of the perio-aesthetic-restorative team to ensure accurate communication
      and provision of the patient's desires. This two-part article compares the
      multidisciplinary treatment approach with the interdisciplinary approach in the
      replacement of congenitally missing lateral incisors.

PMID- 12061060
TI  - Bonding to cast-metal and porcelain-fused-to-metal restorations.

PMID- 12061061
TI  - Provisionalization as a communication parameter for definitive restoration.

PMID- 12061062
TI  - Sinus elevation and single-stage surgical implant placement with a titanium
      osteosynthesis bar.

PMID- 12061064
TI  - Self-appointed dental gurus.

PMID- 12061065
TI  - Dental lasers: Part 2. Soft tissue laser applications.

PMID- 12061063
TI  - The aesthetic post and core: unifying radicular form and structure.
AB  - Use of a post system for the rehabilitation of endodontically treated teeth
      requires traditional planning for the function of the restoration as well as a
      structural and aesthetic strategy for novel technologies in ceramic and composite
      dentistry. Contemporary material options have greatly expanded the clinician's
      ability to rehabilitate the coronoradicular complex. Transilluminating posts,
      bondable fabrics, and high-technology ceramics create exciting possibilities in
      post and core design. The use of bondable materials allows the practitioner to
      unify the structure and morphology of root systems to provide creative solutions
      to challenges heretofore unmet.

PMID- 12061066
TI  - Adolescent dentistry: multidisciplinary treatment for the cleft lip/palate
      patient.
AB  - Congenital labiomaxillary clefts result from the absence or incomplete fusion of
      the maxillary and medial nasal processes with resultant hard and soft tissue
      defects. Comprehensive treatment of these defects requires the collaborative
      efforts of surgeons, orthodontists, restorative clinicians, and laboratory
      technicians. Precise periodontal and orthodontic treatments must be carefully
      coordinated with the restorative plan to ensure sufficient space and tissue
      architecture for the definitive restorations. This article describes the
      multidisciplinary treatment of a cleft lip/palate patient using conservative
      fixed and removable restorative options to provide aesthetic restoration.

PMID- 12061067
TI  - Casting the discovery net too wide: defense attempts to disclose nonparty medical
      records in a civil action.

PMID- 12061068
TI  - [Disability and rehabilitation problems in Russian Federation].
AB  - The authors considered theoretic topics, including terminology aspects, of
      disablement and rehabilitation. The results are up-to-date approaches and
      measures helping to solve disablement problem that remains among priorities in
      the state social policies.

PMID- 12061069
TI  - [Ecologic and social problems of reproductivity in the Irkutsk region].
AB  - The study covered quantitative and structural features, changes in functional
      parameters of female reproductive system, in disorders of pregnancy, childbed and
      newborns in Irkutsk region. The authors demonstrated role and relationships of
      some regional factors--natural, ecologic and technogenic, occupational and
      industrial, social and economic--in formation of reproductivity, disorders during
      1980-1990s.

PMID- 12061070
TI  - [Economic efficiency of sanitation measures at the JSC "Severstal" in the city of
      Cherepovets].
AB  - Using special dispersion dissemination model and software calculating average
      ground concentrations of air pollutants, the authors accomplished a demonstration
      project on determining priority measures in Federal program concerning sanitation
      of environment in Tcherepovets city. Based on cost-effectiveness ratio for
      reducing hazardous influence on public health in the city, the authors carried
      out evaluation and ranking of investment projects and therefore provided
      information to decide on priorities in realisation of investment projects at JSC
      "Severstal".

PMID- 12061071
TI  - [Experience of Grodno regional occupational health center].
AB  - Present structure of Regional Occupational Pathology Center in Grodno was founded
      in 1995 for better organization of occupational health care. Constantly attention
      is paid to higher quality of medical examinations, medical and social
      rehabilitation for patients with occupational diseases.

PMID- 12061072
TI  - [Clinical characteristics of early symptoms caused by chronic exposure to vinyl
      chloride].
AB  - Analysis of clinical signs seen in chronic vinyl chloride intoxication proved
      that early stages of the disease are characterized by functional neurologic
      disorders (vegetoneurosis, astheno-neurotic and astheno-vegetative syndromes) and
      vegetative sensory neuropathy. Periodic medical examinations of workers having
      continuous contact with vinyl chloride proved that neuropathologist plays major
      role in diagnosis and indispensably participates in the examination.

PMID- 12061074
TI  - [Energy metabolism under chronic phosphorus intoxication].

PMID- 12061073
TI  - [Results of gopten monotherapy in drivers having arterial hypertension].

PMID- 12061075
TI  - [Thyroid diseases and microelements metabolism disorders in workers engaged into
      synthetic rubber production].

PMID- 12061076
TI  - [Occupational selection and occupational fitness of physical education and sports
      professionals].

PMID- 12061078
TI  - [Optimization for periodic medical examinations of workers].
AB  - Simple and handy examination methods could be applied to periodic medical
      examination of individuals exposed at work to local vibration, pneumotropic
      pollutants and industrial noise. With these methods, the examinations become not
      burdensome for ordinary internists of general medical institutions.

PMID- 12061077
TI  - [Specification of objects as a basis for social and hygienic monitoring of work
      conditions].

PMID- 12061079
TI  - [Influence of work conditions and climate factors on respiratory diseases
      prevalence among workers of Northern regions].
AB  - The article deals with study covering influence of industrial and climate hazards
      on respiratory diseases prevalence among workers of wash-house situated in cool
      climate, with search of the most informative values for organization of social
      and hygienic monitoring. The results proved that the controlled values should
      include not only dust load and ambient air temperature, but also "duration of
      work in ambient air speed over allowable value", "duration of work in ambient air
      humidity over allowable value", "length of service in North" and "climate area of
      previous dwelling".

PMID- 12061080
TI  - Effects of selenium supplementation on expression of adhesion molecules in
      corticoid-dependent asthmatics.
AB  - Selenium (Se) deficiency attenuates the host immune response, thereby increasing
      the risk of bacterial and viral infections. We have examined the effects of
      selenium supplementation (SeS) in corticoid-dependent asthmatics (CDAs) with
      lowered circulatory Se status. Twenty CDAs (10 males and 10 females, average age
      54.5 yrs) were enrolled into the study. The average duration of the disease was
      10 yrs. The asthmatics were receiving 200 micrograms of Se per day for a period
      of 6 months, in addition to regular treatment with inhaled corticosteroids and
      beta-agonists. The expression of adhesion molecules (CD11a, CD11b, CD18, CD49d,
      CD54, CD62L) on peripheral blood mononuclear cells (PBMCs) of asthmatics and the
      expression of E- and P-selectins, ICAM-1, VCAM-1 on cultured human umbilical vein
      endothelial cells (HUVEC) after stimulation with PBMCs from CDAs before and after
      3 and 6 months of SeS were assessed by standard monoclonal antibodies and
      analyzed by flow cytometry. The concentrations of soluble adhesion molecules P
      selectin, E-selectin, ICAM-1 and VCAM-1 were determined by ELISA method. The
      expression of adhesion molecules on PBMCs: After 3- and 6-months of SeS, a
      decreased expression of molecules CD11a, CD11b and CD62L was observed (p < 0.02,
      p < 0.005, p < 0.003). No changes were seen in the expression of CD18, CD49d
      except for the increased expression of CD54 (p < 0.005). Modulation of adhesion
      molecules expression on HUVEC: We observed a significant increase in VCAM-1, P-
      and E-selectins expressions in the group of asthmatics without SeS in comparison
      with the control group (p < 0.05, p < 0.01, p < 0.05). During SeS a significant
      decrease in molecules VCAM-1, E-selectin (after 3 months) (p < 0.05, p < 0.05)
      and P-selectins and ICAM-1 (after 6 months) (p < 0.05, p < 0.01) were observed.
      Soluble adhesion molecules: After 3 months of SeS we noticed a significant
      decrease in VCAM-1 and P-selectin expressions (p < 0.05, p < 0.05) and after 6
      months the level of VCAM-1 decreased (p < 0.01). The effect of Se on the adhesion
      molecules expression in endothelial cells in vitro experiments: Se blocks the
      expression of adhesion molecules stimulated by IFN-gamma in a dose-dependent way
      after addition of Se into a culture of endothelial cells. Concentration of 10
      micrograms/ml inhibits the increase in expression of ICAM-1 (p < 0.05) but not
      that of VCAM-1, E- or P-selectins. The inhibition of expression in Se
      concentration of 10 micrograms/ml is over 80% (p < 0.01). Our data demonstrate
      that Se is able to affect the adhesion molecules expressions that are crucial in
      the inflammatory process. (Fig. 5, Ref. 22.)

PMID- 12061081
TI  - The influence of selenium supplementation on the immunity of corticoid-dependent
      asthmatics.
AB  - Selenium (Se) is a trace element that is essential for immune functions, and
      protects the immune system from oxidative damage. AIM: The aim of the pilot
      clinical study was to assess the influence of selenium supplementation (SeS) on
      the selected immune parameters analyzed from peripheral blood of corticoid
      dependent asthmatics (CDAs). MATERIAL AND METHODS: Seventeen CDAs aged from 30 to
      74 years (7 females, 10 males) with suboptimal levels of Se in plasma were
      enrolled into the study. The follow up of SeS lasted 96 weeks. It is daily dose
      was 200 micrograms (2 x 2 tbl daily, 1 tbl contained 50 micrograms of Se). Before
      (-4 weeks) and after the 12th, 48th, 72nd and 96th weeks of SeS, the following
      parameters were observed: Epitopes EG1, EG2 expressed on intracellular eosinophil
      (Eo) cationic protein and eosinophil peroxidase, the numbers of CD3, CD4, CD8,
      CD19 and CD3 HLADR positive T lymphocytes (Ly), lymphocyte blastogenesis test
      (LTT) with mitogens concanavalin A, (Conc A) phytohemaglutin (PHA), the levels of
      C3, C4 complement components, activation of complement by classic and alternative
      pathways (CP50, AP50), the levels of immunoglobulins (Ig) G, A, M and total IgE,
      circulating immune complexes (CIC). RESULTS: Epitopes EG1 and EG2 in cytoplasma
      of Eo decreased significantly after 12 weeks of SeS, (p < 0.01) and 96 weeks of
      follow up. In parameters of T cell mediated immunity the relative number of CD3
      HLADR+ T Ly increased after 24, 48 and 96 weeks of SeS (p < 0.0008, p < 0.009, p
      < 0.07). Proliferative activity of T Ly to mitogenes PHA and ConcA in LTT
      decreased significantly after 12, 48, 72 and 96 weeks of SeS (p < 0.0005, p <
      0.009, p < 0.04, p < 0.02, respectively). In humoral parameters activation of
      CP50 decreased after 24, 72 and 96 weeks of SeS to the reference range (p <
      0.001, p < 0.03, p < 0.02) and AP50 after 96 weeks, respectively (p < 0.02). The
      levels of IgG elevated after 24 weeks (p < 0.02), IgA after 24, 48 weeks (p <
      0.0007, p < 0.02, respectively). The level of total IgE significantly decreased
      after 96 weeks of SeS (p < 0.003). CONCLUSION: Our pilot clinical study with the
      CDAs demonstrates the significant changes particularly in functional parameters
      of both cellular and humoral types of immunity. These results support the
      immunomodulating effects of SeS. (Tab. 5, Ref. 15.)

PMID- 12061083
TI  - Pathogenesis of alcoholic neuropathy.
AB  - Chronic alcoholism is a medical, economical and social problem. Motility and
      mental function disorders are among the complications of chronic alcoholism and
      have been known for more than two centuries as "alcoholic paralysis", and are
      caused by alcoholic neuropathy. The pathogenesis of alcoholic neuropathy does not
      appear to be identical with central nervous system disorders which are caused by
      chronic alcoholism and it seems that it results from a failure of the protection
      barrier systems in the peripheral nervous system. To the pathogenesis of
      alcoholic neuropathy includes: 1. direct toxic effects of alcohol on the cellular
      population of the central nervous system and other tissues, especially of
      parenchymatous organs (in particular of the liver), 2. indirect metabolic and
      exotoxic changes mediated by malabsorption, maldigestion and secondary caloric
      and energy deprivation, 3. effects of genetic factors. (Fig. 2, Ref. 23.)

PMID- 12061082
TI  - Decreased consumption of corticosteroids after selenium supplementation in
      corticoid-dependent asthmatics.
AB  - Selenium represents a trace element comprised in enzyme glutathion-peroxidase. It
      is anti-inflammatory activity is based on the elimination of hydroperoxides
      produced in the site of inflammation (scavenger of free oxygen radicals). The
      authors report the results of a pilot study with 17 corticodependent asthmatics
      (7 females, 10 males) aged 30-74 years, supplemented with the preparation of
      selenium (Se), in a daily dose of 200 micrograms during the follow-up lasting 96
      weeks. We demonstrate the reduced consumption of both inhaled corticosteroids,
      manifested after 24 to 96 weeks of Se supplementation (SeS) (21.74 mg vs 15.81
      mg, p < 0.009, 21.74 mg vs 15.32 mg, p < 0.007, respectively) and systemic
      corticosteroids after 48 weeks (294 mg vs 78 mg, p < 0.04) and 96 weeks of SeS
      (294 mg vs 104 mg, p < 0.04). These results correlated with the elevation of Se
      levels both in plasma and erythrocytes (p < 0.0003, p < 0.0003, respectively). No
      adverse effects were seen during the study and the tolerance of preparation was
      good. (Tab. 3, Ref. 17.)

PMID- 12061084
TI  - Clinical neurokinesiology of spastic gait.
AB  - Locomotor control requires a spatiotemporal coordination of passive and active
      forces across the movement system. Both anticipatory and reactive strategies
      operate in locomotor control. Mammalian locomotion is based on a rhythmic,
      "pacemaker" activity of spinal stepping generators. Reflex modification of the
      gait cycle is task-, context- and especially phase-dependent. In spasticity,
      together with disturbed supraspinal control, the phase-dependent reflex
      modulation of the gait cycle is severely impaired and there is altered modulation
      and timing of muscle activation and relaxation during voluntary movement. There
      is also a poor correlation between EMG activity and tension development in the
      spastic muscle. The tension increases without sufficient muscle activation and
      disconnection and dyscoordination between muscle activation, tension development
      and motor performance develops. The pattern of muscle activation and the
      development of increased muscle tone in patients with spasticity may be
      dramatically different in active movement from that observed in clinical testing
      of the passive muscles. Strategies used in the functional treatment of spasticity
      should be aimed at training and activating residual motor function, suppression
      of pathological and unfavourable movement and postural patterns and preventing
      secondary complications. In the 1990s a number of new specific instrumental
      methods and technical equipment supporting gait rehabilitation in patients with
      CNS lesions were developed: rhythmic auditory stimulation and other types of
      rhythmic stimulation, partial body support, usually with treadmill walking,
      complex orthotic support of bipedal locomotion, multichannel functional
      electrical stimulation, usually with programmable computer control, and advanced
      gait trainers. In therapy of spastic gait, the functional goals should be clearly
      determined from the kinesiological point of view of the impairment, and the
      impact on disability and handicap should be considered and a multidisciplinary
      approach is essential. (Ref. 139.)

PMID- 12061086
TI  - Extracorporeal membrane oxygenation in lung transplantation.
AB  - Lung transplantation has become an accepted surgical modality. As the primary
      pulmonary graft failure accounts for almost one third of early deaths, new
      possibilities to positively influence this life-threatening complication had been
      searched for. extracorporeal membrane oxygenation (ECMO) offers an unique
      advantage of overcome the demanding peri- and postoperative period. The authors
      present the advantage of ECMO use, introduce a review of experience with its
      application in lung transplantation. (Fig. 2, Ref. 36.)

PMID- 12061085
TI  - Influence of geomedical factors on Guillain-Barre syndrome incidence in the
      region of western Slovakia.
AB  - During 5-years of follow-up we identified 58 cases of the Guillain-Barre syndrome
      in the Western Slovakia (approximately 1,300,000 inhabitants). The incidence of
      this disease fluctuated between 0.4-1.9 cases per 100,000 persons likewise
      mentioned in the literature. It was interesting to analyse the influence of
      bioclimatic conditions. We found that while higher altitude, cold and humidity
      increased the incidence of the GBS, warm weather had the opposite (beneficial)
      effect. This phenomenon might be related to a higher incidence of upper
      respiratory tract infections, which probably induce the autoimmune related
      disease. (Tab. 1, Fig. 4, Ref. 12.)

PMID- 12061087
TI  - Detection of antibodies in saliva--an effective auxiliary method in surveillance
      of infectious diseases.
AB  - Saliva is a body fluid containing antibodies of diagnostic significance. Unlike
      venipuncture, saliva collection (by brushing the teeth and rubbing the gums) is
      painless, non-invasive, inexpensive, simple and rapid. By using sensitive
      immunoassays in salivary specimens it is possible to diagnose immunoglobulins
      against a wide range of infectious diseases e.g. hepatitis A, B and C, measles,
      mumps, rubella, human immunodeficiency virus, Epstein-Barr virus, parvovirus B
      19, human herpesvirus 6 and Helicobacter pylori infections. Salivary antibody
      testing may provide better access to epidemic outbreaks, children, large
      populations, hard-to-reach risk groups and may thus play a major role in the
      surveillance and control of infectious diseases. (Tab. 2, Ref. 34.)

PMID- 12061088
TI  - HLA system and autoantibodies in primary Sjogren's syndrome.
AB  - The primary Sjogren's syndrome is an autoimmune exocrinopathy in which is
      established a correlation between the production of antibodies and certain HLA
      determinants. A significant number of antigens from A, B, C, DR and DQ loci was
      investigated in 50 patients with primary Sjogren's syndrome with positive
      autoantibodies against dsDNA, ssDNA, Ro (SS-A), La (SS-B), RNP antigens, as well
      as with higher titer of anticardiolipin antibodies from IgM and IgG classes. The
      HLA antigens were investigated by a microlimphocytotoxic test and a prolonged
      test, while the autoantibodies by an indirect immunofluorescency, counter
      electrophoresis and ELISA. A significant correlation was established between HLA
      A1 and HLA-DR3 and the anti-Ro, anti-La, anti-DNA and anti-RNP antibodies, as
      well as between the higher titer of JgM and JgG anticardiolipins and the HLA-A1,
      B8 and DR3 antigens. No association was found between the specific for the
      disease anti-Ro and anti-La autoantibodies and certain genetic markers. The
      achieved results confirm the hypothesis that the autoantibodies' production in
      primary Sjoren's syndrome is to a certain extent genetically determined. (Tab. 1,
      Ref. 5.)

PMID- 12061090
TI  - [Postoperative result for tympanic membrane perforation].
AB  - Ears with tympanic membrane perforation show a wide range of pathophysiology from
      simple perforation to mobility impairment of the ossicular chain complicated by
      sclerotic and/or inflammatory lesions of the middle ear. In surgery on such ears,
      we determine checkpoints and proceed based on the order of procedure. We studied
      postoperative results for 37 ears of patients undergoing tympanoplasty in the 3
      years from June, 1996 to May, 1999. Lesions accountable for mobility impairment
      of the ossicular chain were confirmed and removed in the order of calcified
      tympanic membrane, tip of malleus handle, around the anterior tympanic spur, and
      epitympanum. Success in improving in hearing was 89.2% overall. Conductive
      impairment (air conduction-bone conduction gap) left on the patch test was found
      to differ with the site and range of tympanic and middle ear lesions. This can
      serve as a guide in preoperatively predicting the type of operation required.

PMID- 12061089
TI  - [Changes in plasma inner ear hormones after endolymphatic sac drainage and
      steroid-instillation surgery (EDSS)].
AB  - We treated 33 cases of intractable Meniere's disease with endolymphatic sac
      drainage and steroid-instillation surgery (EDSS), attaining good long-term
      results in vertigo and hearing. To elucidate how EDSS affects the diseased inner
      ear, we examined changes in plasma inner ear hormones after EDSS. Among inner ear
      hormones, plasma vasopressin was significantly decreased after EDSS compared to
      after mastoidectomy. In cases with good long-term results in vertigo and hearing,
      postoperative plasma vasopressin remained lower over the long term than in cases
      with poor results. In cases with negative glycerol test results one year after
      surgery, postoperative plasma vasopressin also remained significantly lower over
      the long term than in cases with positive results. Previous studies reported that
      vestibular neurons projected into hypothalamic supraoptic and paraventricular
      nuclei and that changes in the inner ear pressure were related to plasma
      vasopressin. Taken together with present findings, this suggests that EDSS may
      reduce plasma vasopressin through modification of the diseased inner ear
      environment, resulting in improved inner ear function.

PMID- 12061091
TI  - [Congenital choanal atresia and nasal stenosis].
AB  - The most common form of nasal obstruction in neonates is soft tissue edema, but
      congenital bony nasal anomalies are recognized as an important cause of newborn
      airway obstruction. We reviewed 20 cases of congenital bony nasal abnormalties
      such as choanal atresia and nasal stenosis referred to National Children's
      Hospital between 1996 and 2001. Of the 20, 8 involved choanal atresia (6
      bilateral and 2 unilateral) and 12 nasal stenosis (5 nasal cavity stenosis, 2
      pyriform aperture stenosis and 5 unknown). Six cases of bilateral choanal atresia
      and 5 of 12 cases of the nasal stenosis presented severe airway distress. Most
      cases in respiratory distress required immediate surgical enlargement of nasal
      cavity and stenting with an endotracheal tube for 4 to 8 weeks. Of 12 with nasal
      stenosis, 5 with mild nasal obstruction were treated with nasal drops and 3 with
      mild airway distress required no treatment. Five of 7 (71%) with choanal atresia
      and 1 of 4 with nasal stenosis (25%) required restenosis of the nasal cavity
      after stent removal. Restenosis occurred more often in choanal atresia than in
      nasal atresia. Two of 5 with nasal restenosis required stenting for 1 to 2 months
      again and 1 of those was followed by stenting for more 4 months. Longer stenting
      did not prevent choanal from restenosis, however, no standard stenting protocol
      exists for neonates, highlighting the need for further study.

PMID- 12061092
TI  - [Case of acute deep neck infection in a patient with aplastic anemia].
AB  - Aplastic anemia often causes a life-threatening infection. We report a case of
      deep neck infection in a 30-year-old man with aplastic anemia treated with
      intensive antibiotics after admission, who rapidly recovered without surgery. The
      infection was caused by dental caries with an immunocompromised host via
      hemodyscrasia. He remains free from inflammation recurrence 5 months after
      treatment. We discuss the importance of early, appropriate treatment of deep neck
      infection associated with aplastic anemia occurring in immunocompromised
      patients.

PMID- 12061093
TI  - [Healthy Cities projects].
AB  - This is a review article on "Healthy Cities". The Healthy Cities programme has
      been developed by the World Health Organization (WHO) to tackle urban health and
      environmental issues in a broad way. It is a kind of comprehensive policy package
      to carry out individual projects and activities effectively and efficiently. Its
      key aspects include healthy public policy, vision sharing, high political
      commitment, establishment of structural organization, strategic health planning,
      intersectoral collaboration, community participation, setting approach,
      development of supportive environment for health, formation of city health
      profile, national and international networking, participatory research, periodic
      monitoring and evaluation, and mechanisms for sustainability of projects. The
      present paper covered the Healthy Cities concept and approaches, rapid
      urbanization in the world, developments of WHO Healthy Cities, Healthy Cities
      developments in the Western Pacific Region, the health promotion viewpoint, and
      roles of research.

PMID- 12061094
TI  - [Healthy Cities projects in Europe].
AB  - The WHO Healthy Cities Project has been developed in Europe to place health high
      on the agenda of city decision-makers. It has promoted comprehensive local
      strategies for health and sustainable development. Cities endorse principles and
      strategies, establish project infrastructures, work on specific goals, products,
      changes, and outcomes, and invest in formal and informal networking and
      cooperation. Consistent research and development efforts are contributing towards
      a more evidence-based policy making and to the emergence of a framework to meet
      the demands of the new public health movement.

PMID- 12061095
TI  - [Public participation and empowerment in Health Promotion].
AB  - BACKGROUND: A new model for Health Promotion was proposed by WHO in 1986. PURPOSE
      AND METHOD: The purpose of this paper is to review public participation and
      empowerment in Health Promotion by reviewing case reports and original papers.
      RESULTS: The main results can be divided into two categories, public
      participation, and empowerment, The main results are as follows; 1) Health
      promotion involves the population as a whole in their everyday lives, rather than
      focusing on people who are sick or at risk for specific diseases. 2) The use of
      participatory and empowering approaches in the evaluation process has the
      potential to strengthen the public's capacity for organizational learning and
      improve their own health status. 3) It is possible to improve health conditions
      by using empowerment interventions: 1. The need to adopt an ecological approach
      that simultaneously addresses empowerment. 2. Policy-makers need to take a longer
      term approach to empowerment interventions, including proper longitudinal studies
      to enhance the evidence base for such interventions. 4) Satisfaction is central
      to the delivery of health and human services. The most critical factor in service
      delivery is providing quality care and user merit. 5) In developing people
      oriented health technologies, priority should be given to the availability of lay
      resources and to indigenously developed health practices. 6) Empowerment is the
      most important idea within health promotion. It is often a difficult concept for
      health professionals to grasp since most have been trained to consider health
      care providers as experts and the patient as a recipient of this expertise. 7)
      Health care specialists can contribute considerably to the development of a
      collaborative, family-oriented approach in the development of self care. The
      possibilities for such an undertaking depend on the establishment of working
      relationships at two interfaces: between the health care specialist and his/her
      client families. A framework for developing these relationships is proposed:
      involvement, collaboration, and empowerment. 8) The individual should also be
      given a greater opportunity to actively participate in the design and planning
      health care services. 9) In the Health Promotion program, it is important to
      provide a working and living environment in which respect for each other's
      humanity can be shared.

PMID- 12061096
TI  - [Comparative study on objective-setting public health policy--historical
      background and path dependence].
AB  - The historical background and the path dependence of objective-setting public
      health policy are described in this review. The New Public Health movement
      appeared in the 1980s and was inspired by the Ottawa Charter on Health Promotion.
      This movement is based on the idea that public health is mostly promoted by
      creating a supportive environment for health as well as by individual efforts
      toward a healthy life style. The first objective-setting public health policy
      called Healthy People was proposed in USA, 1979, under the influence of The
      Lalonde Report published in Canada, 1974. Goals and targets were set in order to
      reduce the mortality of American people. This project led to Healthy People 2000
      and Healthy People 2010. In the 1990s, objective-setting public health policies
      prevailed in Western countries, such as United Kingdom, Australia, New Zealand,
      and also in Japan. The objective-setting public health policy is the application
      of the management by objectives in the health policy domain. This policy is
      especially accepted in Anglo-Saxon countries where public sector reform was
      conducted on the basis of the New Public Management theory in the 1980s, which is
      when the WHO Regional Office for Europe started the Healthy Cities project that
      emphasized a network of project cities. The Health 21 in 1999 is another model of
      object-setting public health policy. A comparative study of four different
      objective-setting public health policies (USA, United Kingdom, WHO Regional
      Office for Europe, and Japan) was conducted regarding the goals and domains of
      the targets, methods of targeting, and evaluation of the project. The goals were
      almost identical in the four public health policies, while the domains of the
      targets were different. These differences were explained by the past experience
      of public health policy development in each country.

PMID- 12061097
TI  - [Structural analysis of users' needs from a community pharmacy related to home
      care in a suburban area].
AB  - OBJECTIVES: To clarify the needs of home care service users needs from a
      community pharmacy and the functions related to home care in a suburban area.
      METHODS: A questionnaire on pharmacy services and functions was submitted to 472
      home care service users in a suburban area. Gender, age, family status, presence
      of carers, health condition, home care services being used, prescription and
      pharmacy utilization status, presence of family pharmacy, and recognition of the
      need for drug management guidance by home visiting pharmacists were surveyed as
      well as the users' needs from a community pharmacy and its functions. Using these
      results, principal component analysis was performed. RESULTS: It was found that
      the users had a great need for the following services and functions: adequate
      medication instruction, listening attentively to users, and a good attitude from
      pharmacists and clerks. Meanwhile, the users' need for home care related services
      was relatively low, i.e. counseling about home care and welfare services,
      provision of a home visiting service, and provision of home care supplies. Also,
      principal component analysis indicated that users' needs consisted of five
      components, viz, medical services, material supply, convenience, readiness of
      service provision, and consideration of privacy. Regarding home care related
      services, counseling about home care and welfare services was related to the
      medical services; provision of home care supplies was related to the material
      supply; provision of a home visiting service was related to convenience.
      CONCLUSIONS: It was shown that users did not clearly recognize a service need for
      home care services as a new function of community pharmacies. Rather, users
      recognized the need for home care services connected to these already provided by
      community pharmacies. Therefore, information provision and education are
      necessary so that users can clearly understand the details and merits of the home
      care services which community pharmacies provide.

PMID- 12061098
TI  - [Classification of physical activity and health related variables in men].
AB  - OBJECTIVES AND METHODS: In this study, the relationship of physical activity with
      aerobic capacity and health checkup results were examined among 288 men aged 45.7
      (mean) +/- 8.13 (SD) years. Physical activity was evaluated from a 3-day activity
      record and expressed as metabolic-equivalent (MET) (/day). Total caloric intake
      was evaluated from a 3-day dietary record. VO2 max was measured as the index of
      aerobic capacity, and body mass index (BMI), waist-hip ratio (WHR), % fat, and
      increase in body weight from 20 years old were used as indices of body
      composition. RESULTS: In multiple regression analysis, MET value, % fat, WHR and
      increase in body weight from 20 years old were independently and significantly
      associated with VO2 max. As MET value was a significant predictor, it may be
      important to evaluate physical activity not only during leisure time, but also
      throughout the whole day. In addition, preventing total body fat and abdominal
      fat increase seemed important to maintain and to increase aerobic capacity. To
      grasp the pattern of physical activity more precisely, subjects were classified
      into 6 groups (A: sedentary, B: sedentary + walking, C: sedentary + brisk
      walking, D: sedentary + exercise, E: active, F: active + exercise), and each
      variable was compared using one-way analysis of variance and post-hock test
      analysis (Tukey method). MET value increased in the order of groups A, D, E and
      F. Groups D and E showed no significant difference in the VO2 max and MET value,
      while both groups showed significantly higher values than those of group A.
      Therefore, aerobic capacity differed not only according to the presence of
      habitual exercise, but also according to whether the subjects had an active daily
      life. When sedentary, it seemed important to be active for about 1-hour/day.
      Regarding body fat, group F showed the lowest value in each variable. Systolic
      and diastolic blood pressures, and blood triglyceride levels were highest in
      group A and lowest in group F, suggesting the effects of an active daily life and
      habitual exercise. In group A, the total caloric intake was also highest.
      Therefore, improving the total lifestyle, including diet, was also considered
      necessary. CONCLUSIONS: Classification of subjects according to their pattern of
      physical activity may be useful in health education settings to increase physical
      activity and to prevent life-style-related diseases.

PMID- 12061099
TI  - [Survey of physicians working for AIDS core hospitals on foodborne disease
      reporting].
AB  - OBJECTIVES: To clarify the attitude of physicians toward the diagnosis and
      reporting on patients with foodborne disease after implementation of infectious
      disease prevention and medical treatment to patients as per the Infectious
      Diseases Act of 1999. METHODS: A questionnaire, including experience of diagnosis
      and reporting on patients with foodborne disease, was mailed to all physicians in
      charge of AIDS treatment in medical facilities established as AIDS core
      hospitals. RESULTS: Out of the 391 AIDS core hospitals, 224 (57%) cooperated with
      the survey. Seven hundred and four questionnaires were distributed to physicians
      and 681 (97%) were returned. The number of physicians with experience of
      diagnosing patients with foodborne disease was 391 (57%). One hundred and sixty
      six physicians (57%) answered "Reported occasionally" and fifty-five (14%)
      answered "Never reported". The two main reasons for not reporting were "Did not
      report because I thought there were no other cases" and "Did not report because
      the case was not so severe". CONCLUSIONS: A single or sporadic case must be
      reported by physicians to health authorities to ensure an early alert of illness
      or potential illness that could affect communities.

PMID- 12061100
TI  - [General practitioner's recognition of service cooperation with community
      pharmacists related to home care in a suburban area].
AB  - OBJECTIVES: To clarify the factors affecting a general practitioner's demands and
      the recognition of service cooperation with community pharmacists related to home
      care in a suburban area. METHODS: A questionnaire on pharmacy services and
      functions was administered to 215 general practitioners in a suburban area.
      Gender, age, specialty, length of practice, status of home visiting, requests for
      community pharmacists, awareness of a home visiting service by community
      pharmacists, status of issues about home visiting orders to community pharmacists
      and the criteria for deciding to issue an order, recognition of the necessity of
      a home visiting service by pharmacists, expectation value to the community of the
      pharmacists' participation in the home care service and requests, recognition of
      cooperation with other home care related professions, ease of cooperation with
      community pharmacists, disincentives for cooperation with community pharmacists,
      factors necessary to promote cooperation between practitioners and community
      pharmacists, and factors necessary to promote the home care system were surveyed.
      Using the results, chi 2 test and principal component analysis were performed.
      RESULTS: It was found that the general practitioners' main demands were support
      and management of pharmaceutical therapy. Meanwhile, the practitioners' low
      cognition of pharmacists' home visiting seemed to be one disincentive to
      cooperation with pharmacists. Every practitioner who had issued visiting orders
      to pharmacists practiced home visiting and issued the visiting orders based on
      patients' condition at home. Practitioners who practiced home visiting were more
      active in promoting the home care system and had a better cognition and more
      extensive demands for pharmacists' home visiting compared to practitioners with
      no home visiting. Practitioners with good recognition of cooperation with
      community pharmacists had better cognition, realized the necessity of, and
      expected pharmacist's home visiting compared to practitioners with low awareness.
      However, practitioners' overall recognition of cooperation with pharmacists was
      relatively low. As disincentives, practitioners pointed out lack of acquaintance,
      the unclear function of pharmacists, and no opportunity for cooperation. So,
      enhancing practitioners' awareness of home care, clarifying the pharmacist's
      role, establishing a relationship of mutual trust through information feedback
      and/or exchange based on practice would be effective in promoting service
      cooperation with community pharmacists.

PMID- 12061102
TI  - Is there a doctor in the emergency department?

PMID- 12061101
TI  - Managers and administrators still feeling hard-pressed by governments, survey
      shows.

PMID- 12061103
TI  - The mandate and challenge of increasing diversity in healthcare management.
AB  - The leaders of healthcare institutions should reflect the diversity of the
      communities they serve and the diversity of the patients and families who need
      care. The challenge is one of removing barriers and eliminating naivety as to the
      importance of diversity, how to achieve it and how to manage it. If we are to
      assure excellence in healthcare management, hospitals and health systems cannot
      divorce themselves from this mandate and cannot divorce themselves from this
      challenge.

PMID- 12061104
TI  - Diversity in healthcare management: a regional perspective.

PMID- 12061105
TI  - The Feeding All Tongues Project: developing tools for our growing multicultural
      communities.

PMID- 12061106
TI  - The crisis of September 11: the emergency response of Ontario hospitals and other
      health system partners.
AB  - The horrific events of September 11, 2001, have caused all individuals and
      institutions to step back and evaluate their ability to respond to a crisis of
      previously unimaginable proportions. A media search and incident review of
      Ontario Ministry of Health and Long-Term Care records confirms that no event in
      collective memory has had the potential to yield so many hospital patients. This
      article describes the legislative framework and process by which the ministry
      either leads or supports an emergency response. Within this context, the authors
      analyze the early preparations of the ministry and the Ontario hospital system as
      they readied to accept unknown numbers of patients from the attacks on the World
      Trade Center in New York City and the Pentagon in Washington, DC. While the focus
      of the article is on hospitals, the authors also consider the readiness actions
      taken by the system as a whole, including emergency services, CritiCall and the
      Ontario Hospital Association. The role of support agencies in helping Ontario's
      hospitals respond to the crisis is also examined. Whether the preparations
      undertaken and the commitments made by Ontario's hospitals and other health
      system partners would have been sufficient remains untested at this time.
      However, a careful review of emergency response strategies in order to identify
      any planning gaps is only prudent. This analysis concludes with a discussion of
      what has been learned and some thoughts on how those lessons can assist the
      ministry and our hospitals to remain prepared.

PMID- 12061107
TI  - Health human resource planning: head counting is not enough.

PMID- 12061108
TI  - Nursing best practice guidelines: the RNAO (Registered Nurses Association of
      Ontario) project.
AB  - Best practice guidelines, although a recent phenomenon, have become a global
      movement in nursing. Scholars, practitioners, healthcare organizations,
      governments and the nursing associations have a unique opportunity to enhance
      quality and demonstrate joint accountability to patients, the healthcare system
      and the public as a whole. This article offers insight into the Registered Nurses
      Association of Ontario (RNAO) Nursing Best Practice Guidelines Project. Funded as
      a multi-year project by the Ministry of Health and Long-Term Care in 1999, the
      RNAO project is leading nursing's best practice guideline movement in Canada and
      reaching others abroad.

PMID- 12061109
TI  - The ecological footprint of Lions Gate Hospital.
AB  - The first-ever Ecological Footprint of a hospital was carried out in the summer
      of 2001 in North Vancouver, British Columbia. Although there has been growing
      concern that the healthcare system in Canada might be adversely affecting the
      environment, there have been few analyses of its environmental impact. Lions Gate
      Hospital bravely agreed to participate in this study and have its footprint
      calculated. This displays real leadership, reflecting very positively on the
      hospital's commitment to becoming more environmentally responsible and its
      willingness to open up to scrutiny.

PMID- 12061110
TI  - Energy, health and healthcare.

PMID- 12061111
TI  - The risks of reuse: legal implications for hospitals of reusing single-use
      medical devices.
AB  - There is no doubt that the practice of reuse in hospitals is a reaction to the
      budgetary constraints under which hospitals are operating. However, the costs of
      appropriately monitoring and sterilizing reused equipment as well as the
      significant risk of patient harm and potential liability raise the unavoidable
      question of whether this practice is an advisable one. These costs and risk
      should be carefully examined before a decision about whether to reuse single-use
      devices is made.

PMID- 12061112
TI  - Mixed gender wards: what does the evidence indicate?
AB  - Would adoption of a mixed gender ward policy at the University Health Network
      accelerate the admission of patients to a ward bed, thereby positively
      influencing patient care and improving patient satisfaction? Would reducing
      transfers positively impact staff satisfaction by eliminating an onerous burden?
      How would patients and staff react to the idea of mixed gender rooms? Would
      eliminating transfers have a positive financial impact on the organization?

PMID- 12061113
TI  - Primary care reform in Ontario: the emperor has no clothes.

PMID- 12061114
TI  - Impact of the "new science" of genomics.
AB  - The next 100 years will be the century of biology, just as the 20th century was
      driven by physics and chemistry. The global economy and social outlook for this
      century will be propelled by the new science of genomics. The expanding frontier
      of biotechnology promises life extension, cures for diseases, and enhanced
      quality of life.

PMID- 12061115
TI  - Healthcare emergency preparedness: is the facility ready?

PMID- 12061116
TI  - Analysis of the process of encoding guidelines: a comparison of GLIF2 and GLIF3.
AB  - OBJECTIVES: This study aims to evaluate the use of a modified version of the
      Guideline Interchange Format (GLIF), GLIF3, in the translation of clinical
      practice guidelines into an electronically encoded form such that they may be
      shared among various clinical institutions and settings. METHODS: Based on
      theories and methods from cognitive science, the encoding of two clinical
      practice guidelines into two guideline modeling methods (GLIF3 and an earlier
      version, GLIF2) by two medical informaticians was captured on video and
      transcribed and annotated for analysis. RESULTS: Differing in both content and
      structure, the representations developed in GLIF3 were found to contain a greater
      level of representational detail and less ambiguity than those developed in
      GLIF2. CONCLUSIONS: The use of GLIF3 in the encoding of clinical guidelines
      offers significant improvements due to its greater formality as compared to
      earlier versions of GLIF.

PMID- 12061117
TI  - The use of information graphs to evaluate and compare diagnostic tests.
AB  - OBJECTIVES: The purpose of this communication is to demonstrate the use of
      "information graphs" as a means of characterizing diagnostic test performance.
      METHODS: Basic concepts in information theory allow us to quantify diagnostic
      uncertainty and diagnostic information. Given the probabilities of the diagnoses
      that can explain a patient's condition, the entropy of that distribution is a
      measure of our uncertainty about the diagnosis. The relative entropy of the
      posttest probabilities with respect to the pretest probabilities quantifies the
      amount of information gained by diagnostic testing. Mutual information is the
      expected value of relative entropy and, hence, provides a measure of expected
      diagnostic information. These concepts are used to derive formulas for
      calculating diagnostic information as a function of pretest probability for a
      given pair of test operating characteristics. RESULTS: Plots of diagnostic
      information as a function of pretest probability are constructed to evaluate and
      compare the performance of three tests commonly used in the diagnosis of coronary
      artery disease. The graphs illustrate the critical role that the pretest
      probability plays in determining diagnostic test information. CONCLUSIONS:
      Information graphs summarize diagnostic test performance and offer a way to
      evaluate and compare diagnostic tests.

PMID- 12061118
TI  - Patient-doctor concordance in elderly women's self-reported health and medical
      records.
AB  - OBJECTIVES: To compare the chronic diseases mentioned by elderly women in an
      interview study with those documented in their respective medical records.
      METHODS: The prevalence of positive diagnoses, overall agreement, and the kappa
      coefficient were calculated for each group of diagnoses. RESULTS: The lowest
      overall agreement was observed for psychiatric diseases, followed by diseases of
      the gastrointestinal system. Poor chance-adjusted agreement was found concerning
      diseases of the gastrointestinal system and diseases of the skin. CONCLUSIONS:
      The results suggest that a main reason for discordance was that the elderly women
      feared "losing face" by reporting some diseases.

PMID- 12061119
TI  - The care information system PIK--the fit between user and system.
AB  - OBJECTIVES: The presented laboratory study explores the relationship between the
      care information system PIK and its users, focusing on intuitive program usage,
      occurring errors, the usefulness of the evaluation method, and the role of person
      related variables. METHODS: Three studies were conducted. While thinking aloud, a
      sample of 26 participants performed certain tasks, which were recorded in
      protocols. In addition, the occurring errors were rated in an error taxonomy.
      RESULTS: While the actual use of the program proved quite easy, conceptual
      structuring caused the participants difficulties. These difficulties stemmed
      mainly from problems encountered in generating a clear mental picture of the
      system, and the consequences of the actions. Over time, the program showed a
      positive development. CONCLUSIONS: Discussion of the results focuses on
      implementation processes in the context of usability research. The need to train
      users in the conceptual structure of the program and to build realistic
      expectations are the focus of our outline.

PMID- 12061120
TI  - Systems analysis in health care: framework and example.
AB  - OBJECTIVES: Due to the high complexity of structures and processes in health
      care, thorough systems analyses in health care run the risk of becoming very
      complex and difficult to handle. Therefore, we aimed to support systematic
      systems analysis in health care by developing a comprehensive framework that
      presents and describes potential areas of analysis. METHODS: A framework for
      systems analysis in health care was developed and applied in a health care
      setting. To provide a clear structure, the framework describes the potential
      views and levels of systems analyses in a health care environment. RESULTS: The
      framework comprises five views (roles and responsibilities, information
      processing and tools, communication, business processes, teams structure and
      cooperation) and five levels of analysis (overall organization, organizational
      unit, staff member, role, task). The framework was successfully applied in an
      analysis of the structures and processes of the Department of Child and
      Adolescent Psychiatry of the University Medical Center Heidelberg. CONCLUSIONS:
      The proposed comprehensive framework aims to structure the views and levels of
      systems analysis in the complex health care environment. Our first experiences
      support the usefulness of such a framework.

PMID- 12061121
TI  - Comparison of computer-based information support to clinical research in Chinese
      and Japanese hospitals: a postal survey of clinicians' views.
AB  - OBJECTIVES: The objectives of this research are to examine the current situation
      of computer-based information support of clinical research in hospitals and to
      determine the expectations of clinicians toward clinical research support
      functions of hospital information systems (HISs) in both China and Japan.
      METHODS: 172 clinicians from 42 major hospitals in China (2 groups), and 568
      clinicians from 79 university hospitals in Japan (2 groups), were surveyed by
      postal questionnaire during July and August, 1999. The Kruskal-Wallis test was
      performed to analyze the differences among the groups. RESULTS: The total
      response rate was 66.9%. The result shows that 94.8% of the Japanese clinicians,
      3.5 times more than those in China, use computers almost every day. High
      significance was shown for the frequency of non-HIS based information resources
      used by clinicians between China and Japan (p < 0.001), whereas no significance
      for the frequency of HIS use by clinicians between the China I and Japan I groups
      (p = 0.725) was found. 33.3% clinicians in China thought they could obtain 30-50%
      of the necessary patient data for clinical research from the HIS, about 2 times
      more than in Japan (p = 0.009). CONCLUSIONS: Although the degree of computer
      involvement among clinicians in Japan is much higher than in China, the computer
      based hospital information systems have not been developed well for supporting
      clinical research in both countries. The clinicians expect comprehensive
      computerized patient records (CPRs) and full use of patient related information
      in the existing HISs to support their clinical research.

PMID- 12061122
TI  - Estimation of age-specific reference intervals for skewed data.
AB  - OBJECTIVES: To compare Cole's LMS method with Wright and Royston's Exponential
      Normal (EN) method for estimating reference intervals and generating smooth
      centile curves for the body mass index (weight in kg/height in meters squared)
      measurements of children aged 6 to 13 years. METHODS: In the LMS method, the
      parameters L (the power needed to normalize the data), M (median) and S
      (coefficient of variation) are modeled as smoothed fits of maximum likelihood
      estimates. In the Exponential-Normal method, the three parameters mean, standard
      deviation and skewness are estimated separately using multiple regression
      techniques. RESULTS: The centiles generated by the LMS and EN methods are close
      in most of the age groups. The 2.5th and 97.5th quantiles of the interval of the
      differences between the loss function scores of the LMS and EN methods calculated
      by bootstrap was found to include zero, indicating that the difference in loss
      function scores of the two methods is random and not systematic. CONCLUSIONS: The
      two methods are simple to use and generate comparable centile curves.

PMID- 12061123
TI  - Ordinal classification in medical prognosis.
AB  - OBJECTIVES: Medical prognosis is commonly expressed in terms of ordered outcome
      categories. This paper provides simple statistical procedures to judge whether
      the predictor variables reflect this natural ordering. METHODS: The concept of
      stochastic ordering in logistic regression and discrimination models is applied
      to naturally ordered outcome scales in medical prognosis. RESULTS: The ordering
      stage is assessed by a data-generated choice between ordered, partially ordered,
      and unordered models. The ordinal structure of the outcome is particularly taken
      into consideration in the construction of allocation rules and in the assessment
      of their performance. The specialized models are compared to the unordered model
      with respect to the classification efficiency in a clinical prognostic study.
      CONCLUSIONS: It is concluded that our approach offers more flexibility than the
      widely used cumulative-odds model and more stability than the multinomial
      logistic model. The procedure described in this paper is strongly recommended for
      practical applications to support medical decision-making.

PMID- 12061124
TI  - Representing and processing medical knowledge using formal concept analysis.
AB  - OBJECTIVES: The aim is to show the flexibility, adequateness, and generality of
      formal concept analysis (FCA) applied to expert systems in medicine. METHODS: The
      basic idea of formal concept analysis is to look at a set of objects together
      with their attributes (formal context) under a definite mathematical view. This
      view leads to a mathematical structure, a complete lattice, which can be
      represented graphically. RESULTS: Some examples show that this method is very
      general and can be used to describe diseases, relationships between diseases and
      findings, the inference process, and among others, types of uncertainty. For many
      applications, the adequateness of this method, concerning the underlying
      semantics, can easily be made plausible. CONCLUSIONS: FCA can be used to analyze
      data that can be described by objects and attributes of any kind. The selected
      examples (diseases, patient cases, therapeutic decisions, rules) show the
      usefulness of this method. Although it is not difficult to transform the relevant
      semantics into a formal context in many cases, much more experience is necessary.

PMID- 12061125
TI  - AIDA--experiences in compensating the mutual weaknesses of knowledge-based and
      object-oriented development in a complex dental planning domain.
AB  - OBJECTIVES: Dentistry is a discipline with two properties that pose a serious
      challenge to knowledge based decision support: (1) It has to integrate six
      subdisciplines ranging from conservative measures to invasive disciplines, such
      as implantology; (2) A plan may have to cover a complex treatment often lasting
      one year or more. It is the aim of the AIDA-project to set up a planning strategy
      that is suited to incorporate all dental peculiarities in one methodology.
      METHODS: Generic tasks, that can be assigned to individual persons involved in
      dental treatment, have been designed with the help of KADS. They have been
      integrated into a planning super-structure for the planning of all dental
      solution alternatives, that can principally be applied on the basis of the given
      patient status. RESULTS: Besides an evaluation of the implemented planning system
      itself, it has been evaluated how well the development is supported by (1)
      knowledge-engineering methods and (2) object-oriented methods. CONCLUSION: Common
      knowledge-based tools are not powerful enough for the planning of complex dental
      constructions. Therefore, a solution combining object-oriented and knowledge
      based methods is proposed.

PMID- 12061126
TI  - A resource server for medical training.
AB  - OBJECTIVES: We have developed a RESOURCE SERVER to collect and store various
      elements used by a professor during his lecture. METHODS: The server manages four
      types of objects: ELEMENTS, RESOURCES (set of elements referring to a given
      topic), INDEXES (to organize the resources for further search and use), and USERS
      (to identify providers, users, and access rights). If an ELEMENT s modified, the
      RESOURCE is automatically updated. RESULTS: An example (preparation of an anatomy
      lecture) explains how the RESOURCE SERVER works in three steps: organization of
      the training material, indexing, and retrieval. CONCLUSIONS: The RESOURCE SERVER
      will help instructors develop, update and share pedagogic resources for
      supporting their training courses, lessons and conferences. Moreover, these
      techniques, based on Internet technologies for easy handling of and access to
      these resources, allow local and distant access. Within the general framework of
      the French-speaking Virtual Medical University, the RESOURCE SERVER will
      represent an important link between data collection and its use in intelligent
      pedagogic training.

PMID- 12061127
TI  - Medical Imaging Informatics and Medical Informatics: opportunities and
      constraints. Findings from the IMIA yearbook of Medical Informatics 2002.
AB  - OBJECTIVES: The Yearbook of Medical Informatics is published annually by the
      International Medical Informatics Association (IMIA) and contains a selection of
      recent excellent papers on medical informatics research (http://www.yearbook.uni
      hd.de). The 2002 Yearbook of Medical Informatics took as its theme the topic of
      Medical Imaging Informatics. In this paper, we will summarize the contributions
      of medical informatics researchers to the development of medical imaging
      informatics, discuss challenges and opportunities of imaging informatics, and
      present the lessons learned from the IMIA Yearbook 2002. RESULTS AND CONCLUSIONS:
      Medical informatics researchers have contributed to the development of medical
      imaging methods and systems since the inception of this field approximately 40
      years ago. The Yearbook presents selected papers and reviews on this important
      topic. In addition, as usual, the Yearbook 2002 also contains a variety of papers
      and reviews on other subjects relevant to medical informatics, such as
      Bioinformatics, Computer-supported education, Health and clinical management,
      Health information systems, Knowledge processing and decision support, Patient
      records, and Signal processing.

PMID- 12061128
TI  - Health and medical informatics competencies: call to participate in updating the
      IMIA recommendations.
AB  - OBJECTIVES: On behalf of the International Medical Informatics Association
      (IMIA), its Working Group 1 (WG1) addresses health and medical informatics
      education. METHODS: As part of its mission, WG1 developed recommendations for
      competencies, describing a three-dimension framework and defining learning
      outcomes. RESULTS: Officially approved by IMIA in 1999, the recommendations have
      been translated into seven languages. In 2001, WG1 charged a small group with
      updating the recommendations and consider the work undertaken by others to
      develop competencies. Additional work underway in support of the recommendations
      includes a literature review to help extract the fundamental competencies from
      the recommendations. To ensure the highest quality of input in the updated
      recommendations, WG1 is issuing a call for participation to the international
      informatics community. CONCLUSIONS: Further work with the competencies will
      result in updated IMIA guidelines. These are expected to support the creation of
      a virtual university for health and medical informatics.

PMID- 12061129
TI  - Clinical data retrieval: 25 years of temporal query management at the University
      of Vienna Medical School.
AB  - OBJECTIVES: Today, many clinical information systems include analysis components
      which allow clinicians to apply a selection of predefined statistical functions
      that satisfy typical cases. They are mostly to inflexible to handle complex, non
      standard problems, however. The focus of this paper, therefore, is to present an
      approach that enables clinicians to autonomously create ad hoc queries including
      temporal relations in an interactive environment. METHODS: We developed the query
      language AMAS, which was specifically customized for users from the medical
      domain to flexibly retrieve and interpret temporal, clinical data. AMAS provides
      for a significant temporal expressiveness in data retrieval using time-stamped
      clinical databases and relies on an operator-operand concept for the
      specification of a query. RESULTS: Within the last 25 years, four different
      clinical retrieval systems have been implemented at the Department of Medical
      Computer Sciences, based on the AMAS query language. Currently, these systems
      allow access to the medical records of more than 2 million patients. Physicians
      of 46 different departments at the University of Vienna and Graz Medical Schools
      have made extensive use of these systems in the course of clinical research and
      patient care, executing more than 10,000 queries per year. CONCLUSIONS: We
      discuss a list of 20 issues that represent the most essential lessons we have
      learned in the development of the four systems mentioned above. Amongst others,
      our experiences indicate that the operator-operand concept allows on intuitive
      specification of complex, temporal queries. Further, customization to different
      user classes, based on their statistical background, is essential.

PMID- 12061130
TI  - Design and implementation of a computer decision support system for the diagnosis
      and management of dementia syndromes in primary care.
AB  - BACKGROUND: Diagnosis and management of dementia is a complex process and primary
      care physicians are under-equipped to deal with uncertainties in the provision of
      optimal care for the patient. OBJECTIVE: To develop a computer decision support
      system (CDSS) which could assist physicians with diagnosis and management and
      improve patient care. METHODS: A design group including general practitioners
      derived logic pathways for diagnosis and management of dementia and validated
      them with a multiprofessional expert group. Logic pathways were used to construct
      a comprehensive CDSS rendered as a series of expert consultations. The CDSS was
      inserted into commercially available GP systems and bench and field-tested.
      RESULTS: The complexity of dementia diagnosis and management can be captured in
      logic pathways which can be expressed as decision trees within existing
      electronic patient records. The resulting CDSS appears useable in routine
      practice. CONCLUSION: The impact of this CDSS will be evaluated in a randomised
      controlled trial of educational interventions in primary care.

PMID- 12061131
TI  - Evacuation strategies for disaster planning.

PMID- 12061132
TI  - Patients' drug-information needs: a brief view on questions asked by telephone
      and on the Internet.
AB  - OBJECTIVE: To compare patient characteristics and types of questions from
      individuals who consulted a toll-free telephone number with individuals who
      consulted a free information site on the Internet. METHOD: Characteristics of all
      individuals and the questions they asked on both services in the month of
      February 2000 were analysed. RESULTS: There were several differences between
      individuals who consulted both services. Individuals who asked questions through
      the Internet were younger and consisted of a relatively higher percentage of men
      than individuals who used the telephone. CONCLUSION: Different services can meet
      the needs of different patient groups.

PMID- 12061133
TI  - Hospitalisations caused by adverse drug reactions (ADR): a meta-analysis of
      observational studies.
AB  - AIM: To establish the percentage hospital admission related to adverse drug
      reactions (ADRs) from the data available in the literature. METHOD: Literature
      search in the Medline database, meta-analysis. RESULTS: From the literature it is
      revealed that a considerable part of all hospital admissions are related to
      adverse drug reactions. However, these data are not homogenous, i.e. larger
      studies display a lower percentage of ADR related hospital admission, while
      smaller studies display a higher percentage. Subgroup analysis showed that for
      elderly people the odds of being hospitalised by ADR related problems is 4 times
      higher than for younger ones (16.6% vs. 4.1%). A considerable part of these
      hospitalisations can be prevented. Subgroup analysis revealed that in the elderly
      up to 88% of the ADR related hospitalisations are preventable; for the non
      elderly this is only 24%. Comparatively more elderly people are hospitalised than
      younger ones. Combining these findings, twice as much elderly people are
      hospitalised by ADR related problems than non-elderly, while preventability of
      ADR related hospitalisation might yield 7 times more people in the elderly than
      in the non-elderly. The estimation of the costs of ADR related hospitalisations
      in the Health Care system in The Netherlands is discussed. CONCLUSION: Many
      elderly people are hospitalised by ADR related problems; an important part of
      these hospitalisations can be avoided.

PMID- 12061134
TI  - A survey of ethical issues surrounding supply of information to members of the
      public by hospital pharmacy medicines information centres.
AB  - OBJECTIVES: To examine ways in which medicines information pharmacists approach
      ethical dilemmas encountered in information supply, to appreciate the factors
      affecting any observed variation in responses, and to identify and training
      deficits among medicines information (MI) pharmacists in this area. METHOD: A
      questionnaire was circulated to all medicines information pharmacists working in
      the hospital pharmacy service in the United Kingdom. The survey presented ten
      realistic scenarios involving requests for information on a variety of topics
      from 'lay' callers. MAIN OUTCOME MEASURES: Respondents were asked to identify any
      perceived ethical dilemmas presented by the scenarios and to indicate their
      preferred replies. Details on training given or received in this area were also
      requested. RESULTS: The overall response rate was 151 of 286 questionnaires
      mailed (52.8%), representing 137 discrete DI centres throughout the UK.
      Postgraduate clinical qualifications were possessed by 71% of respondents. Just
      32 (21.2%) indicated that they gave training on ethical issues surrounding
      information supply while 57 (37.1%) said they had received such training. Over
      half (54.3%) had neither received nor delivered training on ethical issues. Of
      the 32 who said they gave training, 21 had received training themselves. Only 4
      (2.6%) said they had a protocol in place for dealing with enquiries from members
      of the public. CONCLUSIONS: There was considerable variation in how respondents
      thought the scenarios might be resolved, emphasising the varying levels of
      appreciation of the issues and lack of a uniform approach to management. An
      interesting dichotomy emerged between liberal and conservative approaches.
      Liberal pharmacists clearly believed that all MI data is in the public domain and
      should be produced and evaluated on request because patients have a "right" to
      it. The conservative pharmacists had a more protective attitude toward the
      patient and believed that patients should not be given information by MI
      pharmacists directly; rather that it should be channelled through the patient's
      doctor. These two approaches are not incompatible, and may be adopted by the same
      pharmacist at different times. From their observations, the authors propose a
      basis of an ethical guideline for MI pharmacists.

PMID- 12061135
TI  - An evaluation of quinolone prescribing in a group of acute hospitals: development
      of an objective measure of usage.
AB  - OBJECTIVES: To develop an objective measure to enable hospital Trusts to compare
      their use of antibiotics. DESIGN: Self-completion, postal questionnaire with
      telephone follow up. SAMPLE: 4 hospital trusts in the English Midlands. RESULTS:
      The survey showed that it was possible to collect data concerning the number of
      Defined Daily Doses (DDD's) of quinolone antibiotic dispensed per Finished
      Consultant Episode (FCE) in each Trust. In the 4 trusts studied the mean DDD/FCE
      was 0.197 (range 0.117 to 0.258). This indicates that based on a typical course
      length of 5 days, 3.9% of patient episodes resulted in the prescription of a
      quinolone antibiotic. Antibiotic prescribing control measures in each Trust were
      found to be comparable. CONCLUSION: The measure will enable Trusts to objectively
      compare their usage of quinolone antibiotics and use this information to carry
      out clinical audit should differences be recorded. This is likely to be
      applicable to other groups of antibiotics.

PMID- 12061136
TI  - Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical
      practice patterns.
AB  - STUDY OBJECTIVES: To assess the knowledge of prescribers regarding intravenous to
      oral conversions of fluoroquinolones, the frequency and time until conversion,
      and to compare prescriber knowledge with the data collected concerning the
      reasons stated for continuation of intravenous fluoroquinolones. DESIGN:
      Prospective chart review and questionnaire. SETTING: Large teaching hospital in
      Paris, France. PATIENTS: Fifty-one males and females. INTERVENTION: Data were
      collected on in-patients receiving intravenous fluoroquinolone for at least three
      days and hospitalized in one of six in-patient units. Patients receiving
      intravenous fluoroquinolone for less than three days were excluded. A
      questionnaire to assess the awareness of a potential conversion was distributed
      to those practitioners who had patients reviewed during the data-collection
      phase. MAIN RESULTS: The questionnaire revealed the ten most common reasons for
      continuing intravenous administration for more than three days. However, the
      physicians agreed that most patients should be converted as soon as possible.
      Practice patterns differed, with only 17 of 51 patients actually converted to
      oral therapy. CONCLUSION: In theory, the clinicians were aware of when to perform
      the conversion. However, in practice, the frequency of conversion was lower than
      optimum. Changes in clinical practice are needed to decrease the costs of
      intravenous therapy, without jeopardizing quality of care.

PMID- 12061137
TI  - Basing pharmacy counselling on the perspective of the angina pectoris patient.
AB  - AIM OF THE STUDY: A participatory action research study design was developed and
      tested in 40 Danish internship pharmacies as part of a 3-year study supported by
      the Research Centre for Quality in Medicine Use. The aim of the study was to
      create a foundation for improving the quality of counselling practice in
      pharmacies by comparing the pharmacy staff's views on, knowledge of and behaviour
      towards a specific patient group with the knowledge, perceptions and medication
      use of the same patients. METHOD: Pharmacy students in their fourth year
      collected data for the study. In 1999, the students carried out 123 qualitative
      interviews with angina pectoris patients and collected 569 questionnaires from
      pharmacy staff in 40 internship pharmacies. RESULTS: The results indicate that
      discrepancies exist between the patients' and pharmacy staff's perspectives on
      important issues such as knowledge about medicines (patients)/provision of
      information about medicines (pharmacy staff), experienced side effects
      (patients)/information about side effects (pharmacy staff), knowledge on
      prevention and lifestyle (patients)/information on lifestyle and prevention
      (pharmacy staff) and expectations of pharmacies (patients)/initiatives started in
      pharmacies (pharmacy staff). CONCLUSION: The study gives reason to believe that
      angina pectoris patients might benefit if pharmacies provided more information on
      the relationship between lifestyle factors and angina pectoris, the possible side
      effects of medicines and the function of medicines.

PMID- 12061138
TI  - [Adenosine production and its role in protection against ischemic and reperfusion
      injury of the myocardium].
AB  - Adenosine exerts cardioprotective effects on the ischemic myocardium. A flexibly
      mounted microdialysis apparatus was used to measure the concentration of
      interstitial adenosine and to assess the activity of ecto-5'-nucleotidase (a key
      enzyme responsible for adenosine production) in in vivo rat hearts. The level of
      adenosine during adenosine 5'-adenosine monophosphate (AMP) perfusion serves as
      an index of the activity of ecto-5'-nucleotidase in the tissue. Endogenous
      norepinephrine (NE) activates alpha 1-adrenoceptors to lead to the activation of
      protein kinase C (PKC), which, in turn, activates ecto-5'-nucleotidase via
      phosphorylation, thereby enhancing the production of interstitial adenosine.
      Histamine-induced release of NE activates PKC, which increases ecto-5'
      nucleotidase activity and augments release of adenosine. Nicorandil, a hybrid of
      an ATP sensitive K+ (KATP) channel opener and nitrate, increases the level of
      interstitial adenosine via cGMP-mediated activation of ecto-5'-nucleotidase.
      Opening of cardiac KATP channels may cause hydroxyl radical (.OH) generation.
      Nitric oxide (NO) facilitates the production of interstitial adenosine, via
      activation of ecto-5'-nucleotidase. However, singlet oxygen (1O2) is a very
      powerful oxidant that causes inactivation of ecto-5'-nucleotidase to result in a
      decrease in the concentration of adenosine in rat heart. Adenosine plays an
      important role as a modulator of ischemic reperfusion injury. The production and
      action of adenosine are intimately linked to the release of NE.

PMID- 12061139
TI  - [Regulation of brain microvessel function].
AB  - The brain microvessels are formed by a specialized endothelium and regulate the
      movement of solutes between blood and brain. The endothelial cells are sealed
      together by tight junctions and play a role as the blood-brain barrier. The brain
      microvessels express GLUT1 as the major form of glucose transporter, aquaporin-4
      as a water channel, and p-glycoprotein as a xenobiotic transporter. Occludin and
      claudin-5 have been identified as the components of tight junction. Increasing
      evidence suggests that the activities of the transporters are regulated by
      adrenergic nerve activity as well as by bioactive peptides such as
      adrenomedullin. The regulation of the activity as well as expression of these
      transporters may become a strategy for prophylaxis and treatment of not only
      cerebral vascular diseases but also neurodegenerative disorders, developmental
      abnormalities and aging of the brain.

PMID- 12061140
TI  - [Function and regulation of production of hepatocyte growth factor (HGF)].
AB  - Hepatocyte growth factor (HGF) was purified as a potent mitogen for rat
      hepatocytes in primary culture and is believed to be the most physiological
      hepatotrophic factor that triggers liver regeneration. HGF is one of the largest
      disulfide-linked cytokines, consisting of a 60-kDa heavy chain and a 35-kDa light
      chain. Human HGF is synthesized as a single polypeptide chain precursor of 728
      amino acid residues that has an appreciable homology with plasminogen, and it is
      processed proteolytically to release an N-terminal signal peptide of 31 amino
      acids and to generate an active heterodimer after secretion. The novel serine
      protease HGF activator and urokinase-type plasminogen activator (u-PA) are
      responsible for the latter extracellular processing. HGF stimulates the
      proliferation of rat hepatocytes in primary culture at concentrations as low as
      10 pM. It also stimulates the growth of various epithelial cells, endothelial
      cells, and some kinds of mesenchymal cells. HGF inhibits the proliferation of
      several tumor cell lines and induces apoptosis of some of them. It also has
      motogenic, morphogenic, anti-apoptotic, angiogenic, and immunoregulatory
      activities. The receptor of HGF is the product of c-met proto-oncogene with
      tyrosine kinase activity that mediates the transduction of multiple biological
      signals of HGF. During liver regeneration, HGF gene expression in the liver,
      spleen, and lung and HGF levels in the blood and liver increase prior to the
      induction of liver DNA synthesis. Liver regeneration is markedly inhibited by
      continuous administration of a neutralizing anti-HGF antibody. HGF production in
      cultured cells is induced by PKC-activating agents, cAMP-elevating agents, PKA
      activating agents, growth factors, and inflammatory cytokines; and it is
      inhibited by TGF-beta, glucocorticoids, 1,25-dihydroxyvitamin D3, and retinoic
      acid. There are many reports on potential application of HGF as a therapeutic
      agent for organ diseases that are difficult to cure such as liver cirrhosis,
      chronic renal failure, pulmonary fibrosis, myocardial infarction, and
      arteriosclerosis obliterans utilizing its potent growth-stimulating activity for
      a wide variety of cells. ELISA kits for assays of serum and plasma HGF levels are
      clinically used to prognosticate the development of fulminant hepatic failure.

PMID- 12061141
TI  - [Involvement of neuronal nicotinic receptor in psychiatric disorders].
AB  - Neuronal nicotinic acetylcholine receptors (nAChR) are a family of ligand-gated
      ion channels that have a pentameric structure composed of five membrane spanning
      subunits. Recent progress in clinical and neurochemical studies have shown that
      neuronal nAChR are involved in some psychiatric disorders such as schizophrenia,
      depression, and anxiety via its stimulating effect of multiple neurotransmitters.
      It has been suggested that the high prevalence of smoking in the patients with
      psychiatric disorders is an attempt to alleviate some psychiatric symptoms using
      the central stimulatory effect of nicotine (a self-medication effort) or to
      alleviate the exacerbated symptoms by nicotine withdrawal. Moreover, recent
      studies with mutant mice lacking specific nAChR subunits and animal models of
      psychiatric disorders have indicated the psychopharmacological role of individual
      nAChR subunits in psychiatric disorders. Thus, it is suggested that alpha 7 nAChR
      is involved in the attention deficit of schizophrenic patients and that alpha 4
      beta 2 nAChR is related to nicotine dependence or the withdrawal symptoms.

PMID- 12061142
TI  - [Pharmacological and clinical profile of the free radical scavenger edaravone as
      a neuroprotective agent].
AB  - The involvement of oxygen radical species has been implicated in ischemic and
      post-ischemic brain cell damage. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one;
      M.W. 174.20, MCI-186, Radicut Injection) has an inhibitory effect on lipid
      peroxidation by scavenging free radicals and prevents vascular endothelial cell
      injury. In rat brain ischemic models, post-ischemic treatment with edaravone
      reduces .OH production and infarction of the ischemic penumbral area and
      suppresses delayed neuronal death. It also improves neurological deficits and
      diminishes deterioration of brain edema observed after ischemia. We investigated
      the efficacy and safety of edaravone in acute ischemic stroke patients. Edaravone
      improved the core neurological deficits, impaired activities of daily living, and
      disability, without serious safety problems. Edaravone was approved in Japan for
      the treatment of acute brain infarction within 24 h after onset in April, 2001.
      We hope that edaravone represents a promising neuroprotective agent that can
      contribute to the treatment of acute ischemic stroke.

PMID- 12061143
TI  - The place of prevention in HIV clinical care: a roundtable discussion.

PMID- 12061144
TI  - Prophylactic panic.

PMID- 12061145
TI  - Prophylactic panic.

PMID- 12061146
TI  - Accidental ingestion of a component of a fixed orthodontic appliance--a case
      report.
AB  - Most dental patients are treated in the supine position, enhancing the risk of
      accidental aspiration or swallowing of foreign objects. This article presents a
      case report of an orthodontic patient who accidentally ingested a section of
      orthodontic wire and coil spring from a fixed expansion device placed in the
      maxillary dental arch. Some guidelines for the prevention of such occurrences in
      the practice and at home, and possible courses of remedial action, are discussed.

PMID- 12061147
TI  - Bilateral submandibular salivary gland swelling--a report of chronic
      sialodochitis with eosinophilia.
AB  - A case of bilateral swelling of the submandibular salivary glands is presented.
      The histopathological features were diffuse periductal sclerosis with a
      lymphoplasmacytic infiltrate which was rich in eosinophils. Some acinar atrophy
      was seen. Salivary ducts showed mucous and squamous prosoplasia, with focal
      inspissated mucin. Numerous dilated and congested blood vessels were prominent
      throughout the stroma. These features overlapped with those of Kimura's disease
      and angiolymphoid hyperplasia with eosinophils. The features of these conditions
      and a differential diagnosis are discussed.

PMID- 12061148
TI  - Dentistry in the 21st century.

PMID- 12061149
TI  - A prospective radiological analysis of fragment displacement in fractures of the
      mandibular condyle: evaluation of 96 consecutive cases.
AB  - A prospective radiological study of 96 patients with mandibular condylar neck
      fractures was undertaken to assess frequency and nature of mandibular condylar
      displacement. Data collected included age, gender, aetiology, and anatomical site
      of fracture and direction of displacement. Men aged 20-29 years sustained the
      majority of condylar fractures. Assault was the major cause of condylar fracture,
      followed by motor vehicle accidents and sport accidents. No anterior or posterior
      displacement of the condyle was noted. Medial displacement of the superior
      fragment was most frequently observed.

PMID- 12061150
TI  - Prevalence of dental caries in 12-13-year-old Jordanian students.
AB  - The purpose of this study was to determine the caries experience of 12-13-year
      old 6th grade students in Jordan. A total of 694 students were selected randomly
      from a list of schools teaching 6th grade students in Irbid, Jordan. The data
      were collected by interview and clinical examination performed by two examiners.
      Dental examinations were done by using dental mirrors and probes under artificial
      light in classrooms and the diagnosis of dental caries was made by the criteria
      recommended by the World Health Organisation (1987). On average students had 24.4
      sound teeth, 2.3 decayed teeth (D), 0.05 missing teeth (M) and 0.16 filled teeth
      (F). The mean DMFT index was 2.51. The D represents 92% of the DMF cases. Of the
      students examined 188 were caries free (27.1%). Of the 19,432 permanent teeth
      examined the highest frequency of dental caries (61%) and fillings (77%) was
      found in first molars, and these were the most commonly missing teeth (67%).
      Second molars and second premolars had the second and third highest frequencies
      respectively, whereas incisors and canines were the least affected teeth (< 2%).

PMID- 12061151
TI  - The effect of radiation on the permeability of human saphenous vein to 17 beta
      oestradiol.
AB  - Radiation therapy is an effective way of treating many forms of cancer, however,
      there are some indications that it may facilitate the development of metastasis.
      The question arises whether radiation therapy during cancer treatment might
      result in an alteration of the permeability of the tissues being treated. This
      alteration in the permeability might lead to metastatic cells escaping from the
      irradiated tissue, leading to the spread of cancer to other sites in the body.
      Because of the above implication, we determined the diffusion kinetics of a
      radioactive marker, 17 beta-oestradiol, through human saphenous vein before and
      after a single half hour exposure to 60 Gy of 60Co gamma-irradiation. Six
      clinically healthy saphenous vein specimens (mean patient age +/- standard
      deviation 57 +/- 13 years; age range 41-77 years) were obtained during cardiac
      surgery. In vitro flux rates of 17 beta-oestradiol were determined through use of
      a flow-through diffusion apparatus immediately after irradiation for a period of
      24 hours. No statistically significant differences could be demonstrated for the
      flux rates of 17 beta-oestradiol through the non-irradiated and 60 Gy irradiated
      saphenous vein tissue. These findings strongly suggest that irradiation at 2
      Gy/min and a total dose of 60 Gy would not alter the permeability of the venous
      wall. We have demonstrated that the in vitro flow-through diffusion method is
      capable of measuring permeability aspects of endothelial cell layers in saphenous
      vein biopsies under conditions resembling clinical reality.

PMID- 12061153
TI  - Efforts to kill coverage mandates run up against powerful forces.

PMID- 12061152
TI  - Long in the tooth.

PMID- 12061154
TI  - Psychologist prescribing: not such a crazy idea.

PMID- 12061155
TI  - Will your state's privacy law be superseded by HIPAA?

PMID- 12061156
TI  - Hospital copayments. At what cost?

PMID- 12061157
TI  - Medicare+EvenMoreChoice: U.S. encourages PPO option.

PMID- 12061158
TI  - 'Real change' in system won't come overnight. Interview by Patrick Mullen.

PMID- 12061160
TI  - Self-funded HMOs on the rise.

PMID- 12061159
TI  - Estimating pediatric primary care provider visits in a capitated environment:
      encounter vs. claims databases.
AB  - PURPOSE: To evaluate the accuracy of insurance claims data indicating
      underutilization of primary care visits by children with special health care
      needs (CSHCN). DESIGN: The study was a retrospective comparison of primary care
      provider (PCP) utilization by 1,131 CSHCN, using secondary data from electronic
      claims-and-encounters databases in a Medicaid health maintenance organization
      (HMO) and a commercial HMO. METHODOLOGY: The study was conducted at the
      Children's Clinics for Rehabilitative Services (Children's Clinics) in Tucson,
      Ariz., a provider of specialty care to CSHCN. All the children in the study were
      eligible for specialty services under Arizona's statewide program for CSHCN and
      were simultaneously enrolled, from Oct. 1, 1995 through Sept. 30, 1996, in either
      one or both of the managed care plans for their primary care. Identical PCP-visit
      information for the same 1-year period was collected from the plans' claims-and
      encounters databases, and the number of primary care visits as computed from both
      databases was compared. PRINCIPAL FINDINGS: Health plan claims data show that
      only 14 percent of the patients visited a PCP during the course of a year. The
      encounter data indicate that 59 percent of the same cohort had PCP visits.
      CONCLUSIONS: Encounter databases capture more information about PCP visits than
      insurance claims databases in capitated environments.

PMID- 12061161
TI  - Wearing black hats ... again.

PMID- 12061162
TI  - Team-care approach catching on.

PMID- 12061163
TI  - Insurers obligated to fight money-laundering schemes.

PMID- 12061164
TI  - [Comparison of the risk of fetal hypoxia in active and expectant management of
      post-term delivery].
AB  - OBJECTIVE: Evaluation and comparison of risk of intrapartum foetal hypoxia in
      expectative and active approach after term of delivery. DESIGN: Retrospective
      analysis. SETTING: Gynaecological and Obstetric Clinic Medical Faculty, Masaryk
      University Brno. METHODS: The authors compared retrospectively two groups. Group
      A comprised 1906 deliveries in 1996, group B 2008 deliveries in 1999. In group A
      194 deliveries after the 41st week term was applied. In group B there were 373
      deliveries with an expectative approach, with inductions after the 42nd week of
      pregnancy. The authors evaluated the number of surgical and induced deliveries in
      after-term pregnancy in both groups and analyzed in indications. The post
      delivery condition of neonates was evaluated in both groups according to the
      Apgar score during the 1st, 5th and 10th minute, In group B the authors had for
      the blood from the umbilical artery. The condition of neonates delivered by a
      surgical approach in group B was made more accurate by the base excess (BE) blood
      from the umbilical artery. The statistical significance of results was evaluated
      by the U-test and chi 2 test. RESULTS: The differences in the condition of
      neonates after delivery between the two groups are insignificant. In the
      expectative approach in 1999 there was a significant decline of the total number
      of induced deliveries and the total number of surgical deliveries. The difference
      in the number of surgical deliveries on account of imminent foetal hypoxia in
      group A and B are statistically insignificant. The number of hypoxic neonates is
      the same in both groups. CONCLUSION: Based on the results of comparison of the
      two groups it is obvious that the expectative approach is safe and medically
      justified. It is not associated with a greater risk of intrauterine foetal
      hypoxia. It does not lead to deterioration of perinatal results and leads to a
      marked reduction of induced deliveries.

PMID- 12061165
TI  - [The fetal ECG--ST analysis in the diagnosis of fetal hypoxia].
AB  - OBJECTIVE: Clinical tests of a new apparatus STAN S21 evaluating the foetal ECG-
      ST section in the diagnosis of foetal hypoxia. DESIGN: Retrospective analysis.
      SETTING: Gynaecological and Obstetric Clinic, First Medical Faculty Charles
      University and General Faculty Hospital, Prague. METHOD: Within the framework of
      clinical tests 27 analyses were made on a apparatus STAN S21 manufactured by
      Swedish firm Neoventa. Contrary to hitherto implemented and published studies, in
      all monitored deliveries the CTG curve was evaluated as well as FpO2 and STAN.
      After each delivery in the neonate the Apgar score and acid-base equilibrium from
      the umbilical artery was evaluated. ST analysis was included mainly in case of
      abnormal CTG records, risk and pathological deliveries. Evaluation was divided
      into two groups: in one delivery was terminated by the vaginal route, in the
      second one by Caesarean section. For evaluation of the CTG curve the FIGO
      terminology was selected (intermediary-suspect) and (abnormal-pathological). For
      evaluation of the FpO2 pathology 30% saturation for 10 minutes was used. In STAN
      analysis important phenomena were evaluated by computer (increase of T wave,
      increase of T/QRS complex and biphasic character of ST). RESULTS: In reduced
      values of the Apgar score (during the 5th minute < 8 points) and the acid-base
      balance from umbilical artery (pH < 7.2, BE > -8) pathological CTG records and
      FpO2 were present in 25%. STAN had in these instances pathological records in
      50%). CONCLUSION: ST analysis is another very effective link in the diagnosis of
      interpartial foetal hypoxia. Initial experience indicates, that STAN will have
      probably a higher diagnostic specificity than CTG and FpO2.

PMID- 12061166
TI  - [Effect of birth weight on neonatal and maternal morbidity in expectant
      management of post-term pregnancy].
AB  - OBJECTIVE: In the retrospective study to evaluate whether the number of newborns
      over 4000 grams weight is greater under expectative management of post-term
      pregnancy and explain its influence on perinatal and maternal morbidity and
      mortality. DESIGN: Retrospective study. SETTING: Gynaecology and Obstetric
      Clinic, Medical Faculty, Masaryk University, Brno. METHODS: Two groups were
      compared. Group I includes 1906 women, who delivered in the year 1996 under the
      active management of the post-term pregnancy with induction of labour in the 41st
      week. Group II includes 2008 parturients who delivered under the expectative
      management of the post-term pregnancy with induction of labour at the end of 42nd
      week. Perinatal mortality, brachial plexus injuries, clavicle fractures,
      Caesarean section rate for cephalopelvic dysproportion and injuries in mothers
      were evaluated. Students T test and chi square test were used for statistical
      purposes. RESULTS: In the group with expectative management of the post-term
      pregnancy there was significantly higher number of newborns over 4000 grams.
      Perinatal mortality and morbidity did not differ between the two groups. There is
      no difference in maternal morbidity as well. CONCLUSIONS: Our results of
      expectative management in post-term pregnancies with newborns over 4000 grams did
      not confirm our worries about higher morbidity both in newborns and mothers.
      There is no need to consider the expectative management of the post-term
      pregnancies to be dangerous.

PMID- 12061167
TI  - [Effect of care in a protected environment on the occurrence of nosocomial
      infections, mucosal colonization of pathogenic microflora and development of
      indicators of immunity in premature infants].
AB  - OBJECTIVE: Prevention of hospital infections in premature infants by treatment in
      protected environment and intentional colonization of the intestine by oral
      administration of non-enteropathogenic E. coli. DESIGN: Original article.
      SETTING: Institute for Care of Mother and Child, Prague. METHODS: Fifty premature
      infants were followed at the Intensive Care Unit. Twenty five infants were
      treated after birth in protected environment and colonized during the first 48
      hours by oral administration of a apathogenic E. coli strain (Vaccine COLINFANT,
      registered and produced in the Czech Republic), 25 infants were treated in
      conventional environment. Bacteriological examinations: stool, nose, throat, ear,
      stomach end other smears were taken 2-3 times during first week and further once
      a week and examined by aerobic cultivation. Immunological examinations: globulin
      levels (IgG, IgM) were estimated in blood samples by ELISA, using specific
      polyclonal antibodies. As early marker of infection T and B subpopulations were
      measured by FACS analysis using double labelling of cells. RESULTS: Birth weight,
      birth length, gestational age, Apgar score, were relatively equal in both groups.
      Time of hospitalization was 7.3 days shorter in infants treated in protected
      environment. Colonization with pathogens (130), number of infections (16%) and
      need for antibiotics (16%) were significantly lower in infants treated in
      protected environment than in infants treated in the conventional one (238
      isolated pathogens, nosocomial infections in 40%, need for antibiotical treatment
      in 48% if infants). Serum IgM levels were lower in infants treated in protected
      environment other immunological parameters did not differ in the two groups.
      CONCLUSION: Treatment of premature and high-risk infants in protected, pathogen
      free environment and intentional colonization with apathogenic E. coli reduced
      significantly the number of isolated pathogens, number of hospital infections,
      need for antibiotics and shortened the time of hospitalization in comparison with
      infants treated in conventional environment.

PMID- 12061168
TI  - [Occurrence of congenital esophageal defects in the Czech Republic 1961-2000-
      incidence, prenatal diagnosis and prevalence according on maternal age].
AB  - OBJECTIVE: To present incidences of the oesophageal atresia or stenosis and their
      maternal age distribution. To analyse maternal age as a possible risk factor for
      the defects studied. DESIGN: Retrospective epidemiological study. SETTING:
      Institute for Care of Mother and Child, Prague, Czech Republic. METHODS:
      Retrospective epidemiological study of oesophageal atresia and stenosis using
      data from the population based register of congenital malformations in the Czech
      Republic over the 1961-2000 period. The main source of data for this paper is the
      database of congenital anomalies at the Institute for Care of Mother and Child in
      Prague (the 1961-1990 period) and the data analysed by the Institute of Health
      Information and Statistics (the 1987-2000 period). RESULTS: Out of the total
      number of 5,589,888 births in the Czech Republic in 1961-2000 period, 804 cases
      of oesophageal atresia and stenosis were registered. Mean incidence of
      oesophageal atresia and stenosis in the period under the study was 1.51 per
      10,000 livebirths. In the 1991-2000 period an increase of incidences of this
      congenital anomaly was revealed in the Czech Republic. By application of the two
      sided 95% CI, statistically significant correlation was found in women of 39
      years of age and older. CONCLUSIONS: Statistically significant increase of risk
      (for age as a risk factor) was found in maternal age groups of 39 years of age
      and over.

PMID- 12061169
TI  - [Importance of ultrasonographic examinations in predicting abortion during the
      first trimester of gestation].
AB  - OBJECTIVE: Draw attention to the possibility to use ultrasonographic examination
      to predict abortion in the 1st trimester of gestation. DESIGN: Review. SETTING:
      Institute for the Care of Mother and Child, Prague. SUBJECT AND METHOD: Review
      article on possibilities of ultrasonographic examination to predict abortion
      during the first trimester of gestation. The article is divided according to the
      images of different extraembryonic and embryonic structures which may be
      important for prediction of abortion during the first trimester of gestation.
      Illustrations are from the author's own observations. CONCLUSION: The presented
      review draws attention to the possible use of transvaginal ultrasonography in
      prediction of gestational complications in early stages of the first trimester of
      gestation. Abnormalities in the size and shape of some embryonic and
      extraembryonic structures make it possible to detect early complications, still
      in the stages of embryogenesis, which may lead to early gestational loss.

PMID- 12061170
TI  - [Premature rupture of fetal membranes].
AB  - OBJECTIVE: Review of issues of premature rupture of membranes. DESIGN: Review
      article. SETTING: Institute for the Care of Mother and Child, Prague, Czech
      Republic, Department of Gynaecology and Obstetrics, Institute for Postgraduate
      Medical Education, Prague, Czech Republic, Department of Gynaecology and
      Obstetrics, Charles University Hospital, Pilsen, Czech Republic. METHODS:
      Critical review of available information on issues of premature rupture of
      membranes with special attention to recommended procedures. RESULTS: Incidence of
      premature rupture of membranes varies from 4.5% to 14% and in about 30% of cases
      it is a cause of preterm delivery, and therefore it contributes substantially to
      perinatal and infant mortality and morbidity. To minimize this effect,
      recommended procedures are stipulated. Different types of clinical situations are
      evaluated and specific measures listed to provide practical guidelines based on
      available information. CONCLUSIONS: Premature rupture of membranes is an
      important topic in perinatology and proper management can affect pregnancy
      outcome. This article provides up-to-date recommended procedures in particular
      situation during pregnancy with focus on practical measures.

PMID- 12061171
TI  - [Pseudo-hydrothorax in peripheral venous catheterization in an extremely
      premature neonate--case report].
AB  - The authors describe very rare complication (pseudopleural effusion) after
      peripheral venous cannulation (Introcan-W 24G3/4 through v. axilaris) in
      extremely premature newborn with birth weight 600 grams, which lead to worsening
      of patient's respiratory insufficiency. Ultrasonographic examination confirmed
      extrapleural process without necessity of surgical intervention. Cannula
      extraction and infusion interruption were followed by spontaneous regression of
      the complication, thereafter artificial ventilation was discontinued and baby was
      discharged.

PMID- 12061172
TI  - [Breastfeeding support in nine Czech maternity hospitals 1998-1999].
AB  - OBJECTIVE: To find out the state of breastfeeding support in prenatal and
      perinatal care and infant feeding in first 6 months in 6 big cities of Czech
      Republic in 1998-1999. DESIGN: Cross-sectional multicentre descriptive study of 6
      medical schools. SETTING: Centre of Preventive Medicine, 3rd Medical Faculty,
      Charles University, Prague. METHODS: In the first year of the study (1998), 1104
      mothers were interviewed by neonatologists at the discharge from 9 maternity
      hospitals. After 6 months, 1019 mothers of the same sample were interviewed again
      by students and staff members of 6 medical schools. Obtained data were analyzed
      in EpiInfo 6 programme using ANOVA and x2 test. RESULTS: 29 percent of mothers
      participated in prenatal classes. 70 percent of newborns were put to the breast
      within two hours after birth. 44 percent of mothers reported problems with
      breastfeeding in the hospital. 77 percent of mothers appreciated the assistance
      with breastfeeding in the hospital. Mothers with higher education, living with
      partner or husband, mothers who participated in prenatal classes, mothers after
      vaginal labour, mothers whose children were put to the breast within two hours
      after birth and mothers who did not have problems with breastfeeding in the
      hospital were breastfeeding fully for significantly longer period. At the
      discharge from the hospital, 93.5 percent of newborns were fully breastfed. At
      the end of the 6th month, 23.1 percent of infants were fully breastfed and 29.9
      percent of infants were breastfed while receiving complementary food. CONCLUSION:
      Breastfeeding rate at the end of the 6th month of age of infants increased
      apparently in mothers from 6 big cities of Czech Republic in comparison with
      national data from 1991.

PMID- 12061173
TI  - [Changes in causes of mortality in very low birth weight neonates].
AB  - OBJECTIVE: Investigate the total mortality and changes in cause-specific
      mortality among very low birth weight (VLBW) infants. DESIGN: Retrospective
      epidemiological study. SETTING: Institute for the Care of Mother and Child,
      Prague, Czech Republic. METHODS: Five hundred and fourteen inborn patients
      (1/1996-12/2001) were retrospectively analysed from our database. We divided our
      study group into two sub-groups according to their birth weight: under 999 grams
      (extremely low birth weight group, ELBW, n = 193) and 1000-1499 grams (very low
      birth weight group, VLBW, n = 321). For statistical analysis the Epi Info 6 (CDC,
      U.S.) software package was used. RESULTS: Total mortality was 9.5% (23.0% in ELBW
      group, 1.2% in VLBW group). The main causes of death in ELBW group were (in order
      to magnitude): sepsis (49%, early to late onset sepsis ratio 1:4), severe
      periventricular-intraventricular haemorrhage grade III and IV (PVH-IVH, 20%),
      respiratory distress syndrome (13%) and other causes (bronchopulmonary dysplasia,
      renal failure, non-oliguric hyperkalemia: 18%). While in the VLBW group there
      were three cases of death due to sepsis and one due to PVH-IVH (1.2%).
      CONCLUSIONS: According to frequency analysis, sepsis is the leading cause of
      death among ELBW and severe PVH-IVH and other causes follow. While looking for
      strength of association in two most often causes (sepsis, PVH-IVH) we found
      highest risk of death among ELBW newborns with PVH-IVH, but not statistically
      significant (OR 2.63; 95% CI 0.68, 9.83). Respiratory distress syndrome, formerly
      reported leading cause of infant death, seems to move to lower order, probably
      due to introduction of new therapeutic tools into clinical perinatal practice
      (corticosteroids, surfactant, new modes of artificial ventilation).

PMID- 12061174
TI  - [Perinatology in the Czech Republic at the end of the millenium. II. Intrauterine
      fetal transportation].
AB  - OBJECTIVE: To evaluate contribution of organizational changes in perinatal care
      among newborns below 1500 grams in Czech Republic in 1990-2000 and international
      comparison of results. DESIGN: Retrospective analysis of selected indicators of
      perinatal care. SETTING: Institute for the care of Mother and Child, Prague.
      METHODS: Analysis of selected national data and their comparison to international
      data from EAPM project "Perinatal Transport in European Countries". RESULTS: Due
      to findings that birth-weight specific early neonatal mortality is substantially
      lower among newborns transported in utero to perinatal centres than among
      newborns transported after birth, the organization of perinatal transport of
      pregnant women with preterm delivery was main task for system of perinatal care.
      The network of perinatal centers and organization of transport "in utero" led to
      high percentage of newborns below 1500 grams treated in specialized centres, even
      compared to other countries. However, according to number of treated patients in
      one centre per year the Czech Republic belongs among countries with small
      centres. CONCLUSION: Organizational measures in system of perinatal care led to
      high percentage of newborns below 1500 grams treated in perinatal centres. This
      concentration contributed together with improved clinical perinatal care to
      important decrease of total perinatal mortality to 4.4@1000 in the Czech Republic
      in 2000. According to number of treated newborns with birth-weight 1500 grams and
      more there are too many perinatal centers of intermediary care in the Czech
      Republic.

PMID- 12061175
TI  - [Comparison of short-term and long-term results after aortocoronary bypass in
      ischemic heart disease in diabetics and non-diabetics].
AB  - In the presented study we have evaluated short-term and long-term results of the
      multiple aortocoronary bypass surgery in the patients with ischemic heart
      disease. We have compared the incidence of the preoperative and postoperative
      complications, short-term and long-term mortality in the group of diabetics in
      comparison to nondiabetics as well as the entry characteristics of both groups.
      Among 2518 patients who were treated with aortocoronary bypass surgery there were
      773 (30.6%) diabetics. The diabetic patients were significantly elder, we have
      found more women among them, more frequent presence of hypertension, chronic
      heart failure and peripheral vascular disease. Contrary in the incidence of the
      previous myocardial infarction we have not found any significant difference
      between both groups. The patients with diabetes mellitus had lower ejection
      fraction of the left ventricle and significantly more extensive coronary artery
      disease which explains that in this group of patients the number of coronary
      bypasses was significantly higher. Comparing the incidence of preoperative
      complications we have not seen any significant difference between the patients
      with and without diabetes mellitus. Out of the postoperative complications we
      have noticed significantly more renal failure, infectious complications, low
      cardiac output syndrome and bleeding disorders in the diabetic patients. The
      duration of hospitalisation in the intensive care unit was significantly longer
      in diabetics (55.11 +/- 89.09 hours to 47.84 +/- 65.18 hours in nondiabetics, p <
      0.05). 30 days mortality in diabetics was 3.75% and 2.4% in nondiabetics (p <
      0.05). This difference was mainly due to the significantly higher incidence of
      multiorgans failure as a cause of death among diabetics (1.3% in diabetics, 0.5%
      in nondiabetics, p < 0.05). 89.1% of nondiabetics and 86.9% of diabetics lived 2
      6 years after aortocoronary bypass surgery (n.s.). We have found the
      significantly higher long-term cardiovascular mortality (2-6 years) in diabetics
      (10.3%) then in nondiabetics (7.6%, p < 0.05).

PMID- 12061176
TI  - [Treatment of diabetic neuropathic defect at the surgery department and at the
      center for diabetic foot care].
AB  - The aim of the study was to evaluate the treatment of neuropathic diabetic ulcer
      at the surgery department and the treatment at the diabetic foot centre at
      dismissal time and 3 months after the dismissal. METHODS: For assessment of
      treatment success parameters of glucose control were used (average of daily blood
      glucose values, glycosylated haemoglobin--HbA1C and glycosylated protein),
      healing of ulcers (Wagner classification), hospitalisation time and number of
      amputations. 22 diabetic patients at the centre and 17 patients at the surgical
      department were observed in this investigation. There was no difference between
      the groups as for the age, glucose control (HbA1C), and severity of diabetic
      ulcers (Wagner 3-4). Local and antibiotic therapies were the same ones. Results
      as median and difference 75th and 25th percentile were evaluated by Wilcoxon test
      for paired data within the groups and by Man-Whitney test between both of the
      groups. RESULTS: In the both group the diabetic control and ulcer healing were
      significantly improved during hospitalisation period, 3 months after discharge
      deteriorate diabetic control and ulcer healing stagnated, however, only in the
      group treated at the surgical department. The hospitalisation time was
      significantly longer in the surgical group in comparison with the centre group
      [median 52 days (35)] vs. [median 31 days (38)], p < 0.01. Amount of
      transmetatarsal and higher amputations was lower at the foot centre in comparison
      with the surgical group (1 vs. 7). Statistical evaluation was not used for low
      amount of amputations. CONCLUSION: Team approach at the centre of diabetic foot
      is effective in the treatment of diabetic foot ulcers, significantly shortened
      the hospital stay, probably decrease amount of amputations. Three months after
      discharge the diabetic control and ulcer healing were significantly better in
      patients treated at the diabetic foot centre.

PMID- 12061177
TI  - [Importance of selected laboratory indicators in the differential diagnosis and
      monitoring of multiple myeloma].
AB  - Multiple myeloma is one of the most common haematologic malignancies. Currently
      there are numerous studies looking for new prognostic markers in multiple
      myeloma. The most important of them are the markers related to proliferative
      activity of neoplastic cells or to size of tumor mass. The subject of this paper
      are the results obtained from investigation of some such laboratory markers in a
      group of patients with monoclonal gammopathies diagnosed at our department in the
      last 3 years. We analyzed blood and bone marrow samples from 51 patients with new
      diagnosed monoclonal gammopathies, 14 of them were patients with monoclonal
      gammopathy of undetermined significance and 37 patients had multiple myeloma. 17
      patients with multiple myeloma were treated by high-dose chemotherapy regimen. We
      assessed significance of selected laboratory markers for differential diagnosis
      of monoclonal gammopathies and for monitoring of activity of multiple myeloma.
      Among the investigated parameters, we verified the significance of cell cycle
      analysis of bone marrow plasmatic population and of the determination of the
      number of circulating myeloma cells in differential diagnosis of monoclonal
      gammopathies. In our opinion, the determination of soluble CD138, beta 2
      microglobulin and neopterin serum levels can be also recommended as helpful
      markers for a solution of this problem. Except of beta 2-microglobulin serum
      level we did not find statistically significant correlation with activity of
      multiple myeloma in any of the investigated parameters.

PMID- 12061178
TI  - [Effect of composition of enteral nutrition on energy expenditure and CO2
      production during periods of average and excessive energy intake].
AB  - The objective of the presented work is to evaluate to what extent the CO2
      production and O2 utilization and energy metabolism at rest (REE) are influenced
      by an excessive nutrient intake and to what extent by the composition of enteral
      nutrition. REE, CO2 production and O2 utilization were investigated in 9 patients
      on complete enteral nutrition by indirect calorimetry in four modifications: I-
      nutrition with 40% kJ fat in a ration 1.2x the energy output at rest at the onset
      of the trial; II--40% kJ and high energy intake (2.4x energy output at rest; III-
      60% kJ fat in ration of 1.2x energy output at rest; IV--60% kJ fat and energy
      intake 2.4x energy output at rest. At 40% (I) and 60% (III) fat content in a
      caloriocally adequate diet the energy output at rest, the CO2 production and O2
      utilization did not differ (mean +/- SD: 1438 +/- 264.1 kcal/24 h, 179 +/- 31.6
      nl/min, 209 +/- 38.1 ml/min vs. 1431 +/- 342.7, 190 +/- 54.2, 207 +/- 46.5).
      Comparison of modifications II and IV revealed a significant (p < 0.05) increase
      of CO2 production on a diet rich in carbohydrates (218 +/- 52.0 vs. 202 +/-
      42.3). The energy output at rest (1674 +/- 389.6 vs. 1661 +/- 378.7), nor O2
      production (240 +/- 54.5 vs. 242 +/- 55.4) changed. Overfeeding with 40% fat (II)
      as compared with (I) led to a rise of the energy output at rest (p < 0.05), O2
      utilization (p < 0.05) and CO2 production (p < 0.01). Overfeeding with lipids
      (IV) led as compared with III to a rise of the energy output at rest and O2
      utilization; CO2 production did not change. CONCLUSION: The composition of
      enteral nutrition according to the described modification does not influences the
      energy output at rest, O2 utilization and CO2 production under conditions of an
      adequate energy intake. In case of an excessive nutrient intake nutrition with
      60% fat does not lead to an increase of CO2 production.

PMID- 12061179
TI  - [Pathogen resistance and other risk factors in the frequency of lower limb
      amputations in patients with the diabetic foot syndrome].
AB  - Patients with diabetes mellitus undergo more amputations due to peripheral
      vascular disease, neuropathy and especially to infection requiring long-lasting
      antibiotic therapy than non diabetic patients. The aim of our study was to assess
      the association between the presence of resistant pathogens presented in diabetic
      ulcers and the frequency of lower limb amputations. METHODS: 191 diabetic
      patients consecutively treated for the diabetic foot in our foot clinic were
      included into two years retrospective study. Peripheral ischemia, the presence of
      osteomyelitis and the incidence of all Gram positive and negative resistant
      pathogens (defined as resistance to all oral antibiotics) especially of resistant
      Staphylococcus species presenting in diabetic foot ulcers were determined.
      RESULTS: 50/191 (26%) patients underwent amputation, of whom 44/50 (88%) had
      minor and 6/50 (12%) had major amputations. 53/181 (29%) patients with diabetic
      foot ulcers had resistant pathogens in their defects. Amputated patients had
      significantly more resistant microorganisms than patients without amputations-
      24/42 (57%) vs. 29/139 (21%); p < 0.001. Resistant Staphylococcus species were
      found in 21% (38/181) of all patients. Patients with amputations had
      significantly more resistant Staphylococcus species in comparison with patients
      without amputations--18/42 (43%) vs. 20/139 (14%); p < 0.001. Significantly
      higher incidence of peripheral vascular disease--79% (38/48) vs. 60% (81/136); p
      < 0.05 and osteomyelitis--69% (33/48) vs. 13% (18/140); p < 0.001--were found in
      patients with amputations in comparison with patients without amputations.
      CONCLUSION: The presence of pathogens resistant to all oral antibiotics and
      especially of resistant Staphylococcus species was significantly higher in
      diabetic patients with lower limb amputations in comparison with patients without
      amputations.

PMID- 12061181
TI  - [Analysis of heart rate variability during the head-up tilt test in patients with
      vasovagal syncope].
AB  - Changes of the autonomous nervous tonus are considered the most important factor
      in the pathogenesis of vasovagal syncope. In order to investigate changes of the
      autonomous tonus the authors examined in patients with vasovagal syncope the
      variability during the head-up tilt test (HUT). In 35 patients with assumed
      vasovagal syncope the authors used a passive HUT (45 mins., 60 degrees) and
      subsequently nitroglycerin-stimulated HUT (0.4 mg s.l, 15 mins.). The heart rate
      variability was evaluated before the onset of the test in a horizontal position,
      immediately after tilting the patient (0 min.), during the 5th, 10th, 15th minute
      of the passive test, during the 5th minute of the nitroglycerin test, during the
      appearance of symptoms and after termination of the test in a horizontal
      position. They compared the results between a group of 20 patients with positive
      HUT (13 men, 36 years) and in 15 patients with a negative HUT (7 men, 32 years).
      The parameters of heart rate variability were during the development of the
      syncope (mean 6.4 mins. after administration of NTG) as compared with
      corresponding values in patients with negative HUT (during the 5th minute after
      administration of NTG) as follows: RR interval 759.6 +/- 248.1 ms vs. 552.1 +/-
      88.7 ms (p = 0.01), SDNN 44.8 +/- 49.6 vs. 29.9 +/- 18.3 (p = 0.001), RMSSD 31.8
      +/- 34.9 vs. 15.2 +/- 10.2 (p = 0.03), LF 4.44 +/- 0.66 lnms2 vs. 4.38 +/- 0.53
      lnms2 (p = 0.82), HF 4.44 +/- 0.57 lnms2 vs. 4.39 +/- 0.45 lnms2 (p = 0.82),
      LF/HF 0.99 +/- 0.03 vs. 0.99 +/- 0.02 (p = 0.90). On development of the first
      presyncopal manifestations the statistical parameters of heart rate variability
      in patients with positive HUT were significantly higher as compared with patients
      with negative HUT, which suggests an increase of the parasympathetic autonomous
      tonus during the development of the vasovagal syncope.

PMID- 12061180
TI  - [Parenteral nutrition in catabolic states using Neonutrin 15%, a new amino acid
      solution].
AB  - Development of amino acid solutions for i.v. use proceeds worldwide, the main
      stimulus being the expanding physiological and pathophysiological findings of
      specific effects of some amino acids and their metabolism and the need to improve
      intensive metabolic care. New Czech preparations in this respect are the series
      of NEONUTRINS 5%, 10% and 15% (Infusia Ltd. Horatev). They are modern
      preparations which meet the pretentious criteria of contemporary amino acid
      solutions (balanced ratio of all essential, semiessential and assisting amino
      acids, a high content of essential and branched-chain amino acids, amino acids
      with specific pharmacodynamic effects). In a multicentre open clinical study the
      authors assessed the tolerance, safety and efficacy of NEONUTRIN 15% in 82
      patients requiring total parenteral nutrition on account of catabolic states of
      different etiology. The preparation was administered repeatedly in an all-in-one
      mixture (together with glucose and lipid emulsions) by means of a central venous
      catheter. A total of 801 doses was administered. The trial provided evidence of
      very good tolerance and safety of the preparation with a practically zero
      incidence of undesirable effects. The follow-up of basic indicators of nitrogen
      metabolism confirmed also the efficacy of NEONUTRIN 15% in comprehensive
      treatment of patients (stabilization of nitrogen balance in the acute stage of a
      disease, normalization of the plasmatic aminogram).

PMID- 12061182
TI  - [Relation between pulmonary ventilation parameters, exercise tolerance and
      quality of life in patients with chronic obstructive lung disease].
AB  - Patients with chronic obstructive pulmonary disease (COPD) do usually have
      decreased tolerance of exercise capacity and impaired quality of life. Several
      studies have shown that exercise capacity is related relatively weakly to lung
      functions in this group of patients. The aim of the present study was to find
      parameter which could better reflect or predict maximal exercise capacity. 19
      patients with the diagnosis COPD with mean value of forced expiratory volume in
      one second (FEV1) 46% predicted (range 21-79%) entering pulmonary rehabilitation
      program were included into the study. Enrolled patients were chosen to cover the
      whole range of airway obstruction severity. Post-bronchodilator static and
      dynamic ventilation parameters were used for evaluation and calculation. Quality
      of live was measured using St. George's respiratory questionnaire (SGRQ),
      evaluating symptoms, activity and impact of the disease with range from 0 (the
      best level) to 100 (the worst level). Values of FEV1 (p < 0.001) and ratio of
      FEV1 to vital capacity (FEV1/VC, p < 0.001) were significantly positively
      correlated with 6 minute walking distance (6MWD). FEV1/VC were closely related to
      6MWD then FEV1. The degree of hyperinflation expressed by residual volume (RV, p
      < 0.005) and by ratio of residual volume to total lung capacity (RV/TLC, p <
      0.001) significantly negatively correlated with 6MWD. Maximal occlusion mouth
      pressures (PImax, p < 0.05) were positively related to 6MWD. Total score of SGRQ
      correlated significantly to maximal exercise capacity. Pulmonary function tests
      and respiratory muscle function have important impact on exercise tolerance in
      patients with COPD. Tolerance of exercise capacity is significantly reflected by
      total score of quality of life in this group of patients.

PMID- 12061183
TI  - [Splenomegaly (clinical importance, diagnosis and therapy)].
AB  - An enlarged spleen is a frequent and important clinical sign. It may be a
      presenting or dominant feature of a number of primary blood diseases as well as
      other clinical disorders of different etiology. The splenic structure consisting
      of the white pulp, the red pulp and intermediate marginal zone together with a
      complicated splenic blood flow enable the spleen to fulfill its functions:
      filtration (phagocytosis), immunological function, reservoir of blood and its
      corpuscules and extramedullary hematopoiesis in certain diseases. Enlargement of
      the spleen may occur as a result of various pathological conditions. This article
      is based on the history, physical examination and laboratory routine test results
      as proposed approach to the differential diagnosis of splenomegaly. Progress and
      changes in management of blood diseases resulted in reappraisal of indications
      for splenectomy. Progress in surgery has made it possible to perform splenectomy
      under videolaparoscopic control avoiding laparotomy.

PMID- 12061184
TI  - [Diagnosis and therapy of pancreatic tumors].
AB  - Pancreatic tumours belong among oncological diseases with a very poor prognosis.
      The total five-year survival is 1-2%. Surgical resection with a curative
      intention increases the probability of five-year survival to 10-20%. However only
      some 10% tumours are diagnosed in the resectable stage. The reason is the low
      specificity of initial symptoms. Earlier diagnosis and improvement of survival
      could be promoted by improvement of imaging methods and endoscopic techniques.
      Improvement of therapeutic results in selected indications can be achieved by
      adjuvant treatment (chemotherapy, radiotherapy, possibly their combination).
      Treatment of inoperable stages of the disease is focused in particular on
      improvement of the quality of the patient's life. Its aim is specially to
      mitigate pain and reduce the consumption of analgesics, to ensure bile derivation
      or release the passage through the digestive tract. This can lead also to
      improvement of the patient's general condition. Despite advances in molecular
      biology of pancreatic cancer the results of systemic treatment remain
      unsatisfactory in advanced tumours. Nevertheless therapeutic nihilism must not
      prevail nowadays. It is necessary to use new findings in diagnosis and therapy.
      Patients with this disease should be included in clinical trials investigating
      optimal therapeutic procedures.

PMID- 12061185
TI  - [Ankle pressure as an indicator of risk for systemic atherosclerosis].
AB  - Contemporary methods of assessment of possible cardiovascular disease based on
      traditional risk factors are not perfect. Therefore new ways are sought. Simple
      and cheap methods include assessment of the blood pressure on the lower
      extremities above the ankles. The finding of a reduced index of ankle pressure
      (ratio of blood pressure above the ankles and pressure on the arm) indicates
      affection of the arteries of the lower extremities and a significantly increased
      risk of cardiovascular diseases (in particular myocardial infarction and stroke),
      independently on other risk factors. Therefore this simple examination should be
      made in middle aged and elderly subjects with a medium and high cardiovascular
      risk in order to define more accurately the health status, and in case of a
      reduced ankle pressure similar provisions should be made as in patients with
      secondary preventive care.

PMID- 12061186
TI  - [Obesity and disorders of the menstrual cycle].
AB  - Obesity, the result of combined genetic and environmental factors, is in recent
      decades one of the most frequent diseases and is encountered mainly in Europe and
      North America. In women it is associated with the risk of several diseases, such
      as diabetes mellitus, osteoarthritis, cardiovascular diseases, sleep apnoea
      syndromee, breast cancer, cancer of the uterus and also with impairment of
      reproductive functions. Already during the last century some observations
      confirmed that a very low or very high body weight is more frequently associated
      with disorders of the menstrual cycle (MC), infertility and poor reproductive
      capacity. However only during the last decades the pathophysiological and
      molecular mechanisms of this relationship were gradually elucidated. The main
      factors which influences the menstrual cycle in obesity are: impaired estrogen
      metabolism, changes in the concentration of sex hormone binding globulin,
      hyperinsulinaemia, and probably also leptin levels.

PMID- 12061188
TI  - Ages of diagnosis, amplification, and early intervention of infants and young
      children with hearing loss: findings from parent interviews.
AB  - A survey was conducted to determine the status of early identification of
      children with hearing loss in Illinois. Over a 3-year period, parents of 77
      children with severe to profound hearing loss were interviewed while attending an
      educational program at a state residential school for the Deaf. Results indicated
      that these children had lower ages of identification than those reported in
      national studies (Arehart, Yoshinaga-Itano, Thomson, Gabbard, and Stredler Brown,
      1998; Harrison & Roush, 1996) and in an earlier study in Illinois (Kittrell &
      Arjmand, 1997). Delays between suspicion and the initiation of diagnosis and
      amplification were reported, and were most often attributed to physicians'
      failure to investigate the possibility of hearing loss. Delays in the onset of
      early intervention services were noted for half of the children. Although the
      study reports progress across all areas, the ages of identification,
      amplification, and early intervention remain higher than recent research
      (Harrison & Roush, 1996; Kittrell & Arjmand, 1997; Marschark, 1998) indicates is
      justifiable.

PMID- 12061187
TI  - [Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) leading
      to the diagnosis of Wilson's disease].
AB  - Authors describe the case of a patient suffering from Thrombotic Thrombocytopenic
      Purpura--Hemolytic-Uremic syndromee. Any cause of the disease was not found,
      except signs of liver injury. The etiology of indefinite liver disease that had
      been diagnosed several years before was examined. Wilson's disease was considered
      as a final eventuality. The finding of 488 micrograms of copper in the dry liver
      tissue confirmed the diagnosis of Wilson's disease in the end.

PMID- 12061189
TI  - Residential psychiatric treatment of emotionally disturbed deaf youth.
AB  - A survey of the literature on emotional disturbance in deaf youth is followed by
      presentation of data on a sample of 58 deaf children and adolescents who were
      patients at the Tampa Bay Academy, a residential treatment facility serving both
      hearing and deaf youth with serious psychological disturbances. These 58 patients
      were compared to a hearing sample of 168 patients on key variables such as
      admitting symptoms, diagnoses, substance abuse, aggressive and assaultive
      behaviors, and sexual abuse. A startling and significant finding was that all of
      the deaf children admitted at age 12 years or younger had strong or confirmed
      indications of sexual abuse. Deaf adolescents had an 85% rate of strong or
      confirmed indications of sexual abuse. A list and brief description of
      residential care facilities serving deaf youth in the United States and Canada is
      reviewed. Only 8 were found that provided specialized services to deaf youth. Of
      those 8, only the National Deaf Academy, Mount Dora, FL, provided exclusive
      mental health and residential care to deaf persons.

PMID- 12061190
TI  - Acceptance of deaf students by hearing students in regular classrooms.
AB  - Peer relations are of great importance during adolescence. Belonging to a group
      and feelings of acceptance or rejection by other members are paramount. The
      article explores the attitudes of 792 hearing students from 10 to 20 years of age
      in 22 different schools in Spain toward the classroom mainstreaming of deaf
      students. In general terms, the results, obtained from a scale similar to the
      Likert and consisting of 19 questions, show that the deaf student is well
      received socially by hearing classmates. Hearing students in general felt that
      deaf students might be better looked after at a special school and that deaf
      students did not work as hard as hearing students. Young female hearing students
      reported the strongest support for mainstreaming of deaf students. Teachers were
      perceived as dedicated and patient.

PMID- 12061191
TI  - Patterns of spelling in young deaf and hard of hearing students.
AB  - The study examined the invented spelling abilities demonstrated by kindergarten
      and first-grade deaf and hard of hearing students. The study included two parts:
      In Part 1, the researcher compared three groups (deaf, hard of hearing, and
      hearing) using posttesting only on the Early Reading Screening Inventory, or ERSI
      (Morris, 1998), and in part 2 collected and analyzed samples of the spelling of
      deaf students in a Total Communication program. Analysis showed that the deaf
      group performed significantly differently in three areas: concept of word, word
      recognition, and phoneme awareness ("invented spelling"; Read, 1971). The deaf
      group outperformed the hearing and hard of hearing groups in concept of word and
      word recognition. But in phoneme awareness, the deaf group performed
      significantly less well than the hearing group. Therefore, the deaf group's
      spelling was followed for 1 year. Deaf students' spelling patterns were not the
      same as those of hearing and hard of hearing students. Deaf students' spelling
      miscues were directly related to the cueing systems of lipreading, signing, and
      fingerspelling.

PMID- 12061192
TI  - Success with academic English: reflections of deaf college students.
AB  - The study identified social, educational, and demographic characteristics of deaf
      postsecondary students who demonstrated strong reading and writing skills.
      Questionnaire information, information from institutional databases, and in-depth
      personal interviews were used to identify factors and characteristics that
      positively influenced the attainment of strong academic literacy skills. Among
      the areas investigated were school experiences, reading and writing experiences,
      study habits and attitudes, communication preferences, personality traits, and
      home and family background. Results of the study generally support previous work
      conducted with talented hearing youth. Several primary themes emerged from the
      study: heavy parental involvement in early education and educational decisions,
      differing modes of communication but extensive family communication, early
      exposure to and intensive experiences with reading and writing, an enjoyment of
      reading, a relatively limited social life, high parental and secondary school
      expectations, the importance of television, and positive self-image.

PMID- 12061193
TI  - Assessing semantic-syntactic features of verbs from thirteen verb subsets.
AB  - There are three major classes of verbs: intransitive, transitive, and linking.
      These three types of verbs can be divided into 13 semantic-syntactic subsets.
      Verbs within each subset give rise to sentences that have similar syntactic form,
      albeit a form distinct from that of sentences associated with other subsets.
      Preliminary research found that more than 90% of sentences written by children or
      for children contain verbs from 1 of the 13 verb subsets. The sentence form
      associated with each verb subset might be viewed as a "sentence template" that
      operationally defines a fixed set of 13 underlying semantic-syntactic
      relationships essential to communication. A strategy for assessing a child's
      knowledge of verbs from each subset is described.

PMID- 12061194
TI  - [Patenting human genes].
AB  - The problem of patenting of human genes, which was discussed at the Workshop
      organized by OECD, has become very actual due to granted patents that concern
      testing of genetic disposition for breast cancer. Companies that had made large
      investments into this research clearly support patenting of their discoveries.
      But such patents can reduce general accessibility of genetic testing. Existing
      laws, and namely the Directive of the European Council unfortunately are not
      unambiguous and allow rather free explanation.

PMID- 12061195
TI  - [Tularemia--history, epidemiology, clinical aspects, diagnosis and therapy].
AB  - Tularemia was first described 90 years ago by McCoy as a disease of animals. At
      the beginning of twenties it was recognised by E. Francis as a disease
      transmittable from animals to man. Tularemia is caused by a gram-negative microbe
      Francisella tularensis. Epidemiological and clinical manifestations of the
      disease are highly diverse. The characteristic sign is the primary complex
      consisting from an initial ulceration and a regional lymphadenitis. In the Czech
      republic tularemia was first identified in 1936 in the south of Moravia and for
      the next years it occurred sporadically or in epidemic form also in the western
      Moravia, in north-west and east of Bohemia. It affected persons manipulating with
      the diseased animals, namely with hares, workers in animal farms and those
      working in cold sections of sugar mills. After a longer pause, during the last
      six years, the incidence of tularemia has increased again. That is why we decided
      to renew the understanding of the disease.

PMID- 12061196
TI  - [Concomitant radiochemotherapy in rectal tumors].
AB  - Requirements for improved cancer control led to the testing of the combined
      modality therapy for many types of cancer. This review attempts to analyse
      possibilities of the simultaneous application of both strategies in the treatment
      of rectal cancer. Postoperative radiochemotherapy has been shown to be effective
      in rectum carcinomas. Preoperative combined-modality therapy can ensure
      downstaging (T3, T4). Operation was carried out 4 to 6 weeks after the end of
      preoperative therapy.

PMID- 12061197
TI  - [Effect of a dialysis solution with icodextrin on ultrafiltration and selected
      metabolic parameters in patients treated with peritoneal dialysis].
AB  - BACKGROUND: To date, peritoneal dialysis has been performed almost exclusively
      using dialysis solutions containing glucose as the osmotic agent. Use of these
      solutions is fraught with problems regarding adequate fluid removal from the body
      and is also associated with undesirable metabolic effects; hence the search for
      alternative osmotic agents. A dialysis solution with the glucose polymer
      icodextrin generates ultrafiltration on the principle of colloidal osmosis. The
      aim of the study was to establish the effect of icodextrin-base dialysis solution
      on the magnitude of ultrafiltration and evaluate selected metabolic parameters of
      patients treated by ambulatory peritoneal dialysis. METHODS AND RESULTS: A total
      of 9 patients whose glucose-based solution was replaced by an icodextrin-based
      solution during the night-time exchange were evaluated. A control group of 9
      patients used glucose-solution during all exchanges. Night-time bag
      ultrafiltration, blood pressure, and the serum levels of lipids, insulin, leptin,
      maltose, and amylase were determined before icodextrin administration (time 0),
      at one-month intervals (time 1, 2, 3), and one month after study completion (time
      4). In icodextrin-treated patients, ultrafiltration rose from 246.5 +/- 60.5 ml
      (mean +/- SEM) at time 0 to 593.1 +/- 87.4 ml; p < 0.01, at time 1, to 547 +/- 67
      ml; p < 0.05, at time 2, and to 586.7 +/- 58.8 ml; p < 0.01, at time 3, the
      icodextrin administration led to a rise in maltose from 0.02 +/- 0.01 g/l at time
      0 to 0.1 +/- 0.1 g/l; p < 0.01, at time 1, to 1.0 +/- 0.09 g/l; p < 0.01, at time
      2, and to 1.1 +/- 0.09 g/l; p < 0.01, at time 3, with a fall to zero values at
      time 4 (NS). Icodextrin administration was followed by a decrease in leptinemia
      from 34.6 +/- 17.2 ng/ml at time 0 to 21.7 +/- 8.9 ng/ml; p < 0.05, at time 1, to
      21.4 +/- 9.5 ng/ml; p < 0.05, at time 2, and to 15.9 +/- 24.1 ng/ml; p < 0.05 at
      time 4. Insulin and lipid levels were not affected. There was no change in the
      above parameters in the control group. Icodextrin-treated patients reduced their
      antihypertensive medication, but not statistically significantly. CONCLUSION:
      Icodextrin administration significantly increase ultrafiltration thus providing
      for effective control of hydration status without the need for high-level glucose
      based dialysis solutions. The use of a glucose polymer-based dialysis solution is
      associated with a significant yet reversible rise in serum maltose. The decrease
      in leptin may signal a reduction in body weight after replacing glucose in
      dialysis solutions with icodextrin, or enhanced rates of leptin elimination as a
      result of ultrafiltration-induced convective transport.

PMID- 12061198
TI  - [Nitric oxide in the treatment of acute respiratory distress syndrome].
AB  - BACKGROUND: Nitric oxide (NO) is a selective pulmonary vasodilator effective in
      the treatment of pulmonary hypertension and hypoxemic respiratory failure.
      Reports in the Czech literature on the results of its therapeutic use are still
      scarce. METHODS AND RESULTS: Effects of inhaled NO on the changes of PaO2/FiO2
      were assessed in the retrospective study. Records of artificially ventilated
      patients suffering from acute respiratory distress syndrome (ARDS) were reviewed.
      Daily highest NO dose, the highest PaO2/FiO2 ratio, duration of NO administration
      and death or survival of the patient was noted. Survivors and nonsurvivors, as
      well as responders (rise of PaO2/FiO2 by at least 20%) and non-responders were
      compared using Mann-Whitney and ANOVA test, alpha = 0.05. 16 patients were
      entered into the study, 13 (81%) responded positively to NO administration, the
      mortality was 56%. Comparing the age, NO dose, duration of its administration and
      APACHE II score in survivors and non-survivors, in respondents and non
      respondents no differences were found. After NO administration the PaO2/FiO2 rose
      both in survivors and non-survivors (p < 0.0005). In survivors the response of
      oxygenation was more pronounced, although the difference did not reach the
      statistical significance (p = 0.07). On the days 1-3 the PaO2/FiO2 ratio was
      higher in survivors (p < 0.05). CONCLUSIONS: Despite the transient increase in
      oxygenation after NO administration, mortality of patients with ARDS remained
      high. NO administration could not be considered the standard method of treatment
      of patients with ARDS in intensive care.

PMID- 12061199
TI  - [Epithelioid hemangiosarcoma of the thyroid gland].
AB  - Authors present a case of epithelioid haemangiosarcoma of the thyroid gland in a
      54-year-old female with a history of eufunctional nodular goitre. The patient was
      treated by total thyroidectomy with extirpation of cervical lymph nodes and by
      subsequent chemotherapy. The tumour behaved highly aggressively with early
      generalization and unusual way of metastatic spread into the wall of the stomach
      and duodenum. The patient died 3 months after the surgery due to therapeutically
      unmanageable bleeding into the GIT. The clinico-pathological aspects of the case
      are discussed.

PMID- 12061200
TI  - [Angiographically marginally significant coronary stenoses--postponement of
      intervention based on measurement of myocardial fractional flow reserve].
AB  - INTRODUCTION: When evaluating angiographically marginal coronary stenoses (i.e.
      40-70% reduction of the diameter of the arterial lumen) it is under certain
      conditions difficult to decide on their actual functional impact. Assessment of
      the fractional flow reserve (FFR) is a simple method based on assessment of
      intracoronary pressures during pharmacologically induced hyperaemia. For the
      severity of stenosis according to previous studies the liminal values is FFR
      lower than 0.75; furthermore it was proved that intervention of angiographically
      marginal stenoses with FFR values of 0.75 or more can be safely postponed.
      OBJECTIVE: Test the safety of FFR examination and take in a group of patients
      with marginally severe stenosis further steps according to results of FFR
      assessment. MATERIAL AND METHODS: During the period from January to Juky 2000 FFR
      assessments were made in a total of 34 patients (11 women, 23 men, mean age 62 +/
      12 years) who suffered from marginal stenosis of some coronary vessel. The FFR
      examination took place under pharmacologically induced hyperaemia after
      intracoronary adenosine administration. RESULTS: Measurements were made in a
      total of 41 stenoses. Only in two a value lower than 0.75 was found. In these
      patients coronary intervention was implemented; intervention was also made in two
      patients on account of technical problems and inconsistent results of FFR
      measurements. A FFR value of 0.75 or less was found in 37 stenoses (90%) and
      intervention was therefore postponed. Examination and the immediate subsequent
      course were without complications. CONCLUSION: According to initial experience
      FFR examination is a safe, simple and easily reproducible method. Based on the
      results of assessment and knowledge of the accomplished studies in the group of
      marginally significant stenoses in a great proportion of patients coronary
      intervention was postponed.

PMID- 12061201
TI  - [Echocardiographic quantification of changes in left ventricular kinetics in
      patients during hospitalization for a first myocardial infarct and treated with
      direct angioplasty].
AB  - The authors quantified the changes of left ventricular kinetics during
      hospitalization after a first transmural myocardial infarction treated by direct
      percutaneous coronary angioplasty. For accurate quantification a group as close
      as possible to experimental conditions was selected. 64 patients (43 men), mean
      age 67.3 years (44-86) were investigated. The echocardiographic examination was
      made within 24 hours after admission and on discharge (9.8 days). A 16-segment of
      the left ventricle was used, the kinetics were evaluated by 4-grade score. The
      ejection fraction was calculated by Simpson's method from 4 cycles, the wall
      motion score index was calculated by the standard procedure. During the follow up
      period significant improvement of left ventricular kinetics occurred. The
      ejection fraction improved from the original 46 +/- 11% (median 41.5) to 51 +/-
      11% (median 50.0) (p < 0.005), the wall motion score index from 1.6 +/- 0.3
      (median 1.65) improved to 1.5 +/- 0.3 (median 1.60) (p < 0.005). Improvement of
      the investigated parameters correlated with the clinical course, 87% of the
      patients being free of any complications. CONCLUSION: Successful direct
      angioplasty leads in patients with a first myocardial infarction to improvement
      of the ejection fraction and wall motion score index already during the first 10
      days.

PMID- 12061202
TI  - [Direct percutaneous transluminal coronary angioplasty in patients with acute
      myocardial infarct treated at the Cardiac Center of the General Medical School
      Hospital in Prague: a 1-year retrospective study].
AB  - Direct percutaneous transluminal coronary angioplasty (d-PTCA) in patients with
      acute myocardial infarctions (AIM) has become an alternative of thrombolytic
      treatment. If the involved department has adequate experience the success rate of
      the procedure is high and the immediate and long-term results are better than
      those of thrombolysis. Moreover contrary to thrombolytic treatment successful
      percutaneous coronary intervention in AIM is more beneficial for patients also
      later than 6 hours after the development of infarction pain. In the Cardiocentre
      of the General Faculty Hospital (GFH) patients with AIM are constantly attended,
      i.e. those indicated for reperfusion therapy are treated solely by the d-PTCA
      method. OBJECTIVE AND METHOD: Retrospective analysis of d-PTCA in AIM made during
      the annual period from Jan. 1 2000 to Dec. 31 2000. Into the observation study
      patients were included with clinical and/or ECG signs of AIM when the period from
      the onset of pain to the beginning of intervention did not exceed 12 hours. All
      patients were given before the procedures 500 mg of acetylsalicylic acid and
      10,000 u. heparin. Cardiac catheterization was implemented by the percutaneous
      Seldinger technique via the a. femoralis l.dx., in exceptional cases from the
      left femoral artery. An approach via the a. radialis and/or a. brachialis was not
      used in any of the patients. From the investigation patients were excluded who
      had before the percutaneous coronary intervention (PCI) a thrombolytic
      preparation (so-called rescue-PTCA). RESULTS: During the mentioned period in the
      Cardiocentre of the GFH a total of 673 PTCA were performed, incl. 127 (18.9%) d
      PTCA in patients with AIM. In the mentioned group of 127 patients subjected to
      intervention were 87 (68.5%) men and 40 (31.5%) women. The mean age of the men
      was 59.1 +/- 12 years and the mean age of the women 68.2 +/- 12 years. As to the
      main risk factors of coronary atherosclerosis arterial hypertension was present
      in 48%, smoking in 42%, diabetes in 23% and hyperlipoproteinaemia in 31% of the
      treated patients. More than one third of the patients had a history of myocardial
      infarction (38%). The infarcted artery was the r. interventricularis anterior
      (LAD) in 51 (40.2%), the right coronary artery (RCA) in 54 (42.5%), the r.
      circumflex (LCX) in 16 (12.6%), the left main coronary artery in 2 (1.6%) and the
      bypass in 4 (3.1%). Multiple coronary affections were recorded in 80 (63%)
      patients, affections of one artery in 47 (37%). Primary procedural success (flow
      TIMI 3/2) was achieved in 121 patients (95.3%). Normal flow through the infarcted
      artery TIMI 3 was achieved in 118/127 (85.8%) patients. In 91 (71.7%) into the
      infarcted artery a coronary stent was implanted, during hospitalization no
      subacute stenosis of the stent developed. The mean period between the onset of
      infarction pain--injection was 4.4 +/- 2.3 hours. The mean period of the entire
      procedures was 48 +/- 14.5 minutes. As contrast material only non-ionic contrast
      substances were used (Iomeron 350) with a mean consumption of 150 ml per patient.
      The mean skiascopic time was 13.6 +/- 1.8 min. A total of 9 (7.1%) patients were
      treated with GP IIb/IIIa receptor blockers (abciximab). The total hospitalization
      mortality of the intervened group was 7.1% (9 patients). In a sub-group of 9
      patients who at the onset of the procedure were in cardiogenic shock 3 (33%)
      died. The hospitalization mortality of the sub-group of patients with AIM without
      cardiogenic shock, treated with d-PTCA was 5.1% (6/118). During hospitalization
      the authors did not observe any intracranial haemorrhage. DISCUSSION: The group
      of subjects with AIM subjected to catheterization who are treated by d-PTCA is
      relatively numerous in our department. According to a number of clinical studies
      successful d-PTCA in AIM gives better short-term and long-term results as
      compared with thrombolytic therapy. The primary success rate of d-PTCA was high
      and the hospital mortality was low and comparable with contemporary data in the
      literature. CONCLUSION: Direct PTCA is effective treatment in patients with acute
      myocardial infarction. The authors results confirm the high procedural success
      rate and acceptable hospital mortality. These favourable results of an invasive
      approach to treatment of AIM must be compared in future with bolus thrombolytic
      treatment by new types of thrombolytic preparations in combination with anti
      platelet treatment with blockers of platelet glycoprotein receptors IIb/IIIa
      with/or without subsequent percutaneous coronary intervention.

PMID- 12061203
TI  - [Occurrence of autoimmune complications in patients with chronic myelocytic
      leukemia during treatment with interferon alfa].
AB  - Several prospective randomized studies have shown that the treatment of chronic
      myeloid leukemia with interferon alfa (IFN alpha) prolongs the survival by
      comparison with conventional chemotherapy. However, long-term treatment with
      Interferon alfa (IFN alpha) can produce or exacerbate immune-mediated
      complications (IMC). The purpose of this study was to analyze the experience with
      IMC in patients with chronic myelogenous leukemia (CML) undergoing IFN alpha
      treatment. PATIENTS AND METHODS: The occurrence of IMC was evaluated in 76
      patients (47 male; 29 female) with Philadelphia chromosome (Ph)-positive CML. The
      median of age was 45 years and the duration of disease was 3.9 years. Diagnostic
      criteria of IMC were performed in patients with sign and symptoms suggestive of
      particular disorders. RESULTS: Well-documented and clinically evident
      complications developed in 7 patients after a median of 19 months (range 1-84) of
      IFN alpha treatment. These included 9.2% patients with Ph-positive CML treated
      with IFN alpha-containing regimens. Hypothyroidism (H) occurred in 1 patient
      (1.3%), immune-mediated hemolysis (HEM) in 2 patients (2.6%) and connective
      tissue disorders (CTD) in 4 patients (5.3%) [2-SLE, 1-Raynad's syndrome and 1
      mixed connective tissue syndrome (MCTS)]. IFN alpha was discontinued in 3
      patients and the dose was reduced in 2 patients. Five of 7 patients (75%) with
      immune-mediated complications had some degree of cytogenetic response at the time
      of the event. The association with female sex was strong and significant (86% vs
      33.6%, x2; 48; p = 0.02). CONCLUSION: The frequency of IMC of clinical relevance
      with interferon alfa therapy in CML increased (long-term therapy). The patients
      treated with interferon alfa should be monitored for sign and symptoms of
      autoimmunity.

PMID- 12061204
TI  - [Therapeutic effectiveness of cladribine and cellular immunodeficiency--related
      effects in hairy-cell leukemia?].
AB  - The high therapeutic efficiency of lymphotoxic purine analogues, pentostatin and
      cladribine in hairy cell leukaemia which express the antigen CD25 (alpha chain
      interleukin-2 receptor) suggests the hypothesis whether protracted cellular
      immunodeficiency after treatment does not represent an important mechanism of
      control of this specific lymphoproliferation. The authors analyzed a group of 45
      patients with CD25-positive hairy cell leukaemia treated with cladribine. In
      addition to the therapeutic response they evaluated also the state of cellular
      immunity during the subsequent months and years following cladribine
      administration. The regression lines of the development of different sub
      populations CD4, CD8 and CD56-positive cells, interleukin-2 and its soluble
      receptor were evaluated separately in patients with persistent remission and
      patients with growth of the tumourous mass. Although this retrospective analysis
      provides only limited information we can deduce from it a long-term decline of
      CD4 lymphocytes correlating with the relatively low incidence of clinical
      progression of hairy cell leukaemias. The results of this clinical observation
      are consistent with some reported clinical and experimental observations.

PMID- 12061205
TI  - [Hepatic encephalopathy after TIPS--retrospective study].
AB  - Hepatic encephalopathy (HE) is the main neuropsychiatric complication in
      cirrhosis of the liver. It develops slowly, begins by alteration of sleep and
      proceeds via flapping tremor to sopor, coma. Among known factors which promote
      its development are age, high dietary protein intake, haemorrhage into the GIT
      and the use of sedatives. Transjugular portosystemic anastomosis (TIPS) as a
      therapeutic method in complications of portal hypertension is associated with a
      higher incidence of HE. The objective of the work was to assess by retrospective
      investigations of patients with cirrhosis of the liver after TIPS the incidence
      of clinically significant HE and identify risk factors for the development of HE.
      MATERIAL AND METHODS: The group comprised 256 patients with cirrhosis of the
      liver after TIPS. This number included 59 diabetic and 197 non-diabetic patients,
      7 patients suffered from chronic renal insufficiency and were in a regular
      dialyzation programme. The presence of HE was evaluated clinically. RESULTS: HE
      was found in 51% patients above 60 years of age, vs. 27% in younger patients (p =
      0.002). The authors did not observe a difference in the incidence of HE in
      relation to sex, stage of cirrhosis, diameter of the stent nor the drop of the
      portosystemic gradient. In diabetic patients HE developed in 45.8% (27 of 59), as
      compared with 30% (59 of 197) in non-diabetic patients (p = 0.02). Multivariance
      analysis revealed however that the group of diabetic patients had a higher
      average age and thus the incidence of HE was statistically significantly
      conditioned by age and not by the presence of diabetes. CONCLUSION: The risk
      group for HE in our patients were those above 60 years of age and patients with
      another than ethylic etiology of liver cirrhosis. There was no direct
      relationship between the development of HE and other investigated parameters.
      Although there was no difference in the incidence of HE in relation to the
      diameter of the inserted stent or portosystemic gradient and its reduction, in
      case of unsuccessful conservative treatment with lactulose and diet, HE can be
      resolved by narrowing of the shunt by insertion of a reducing stent.

PMID- 12061206
TI  - [Are we underestimating the nephrotoxicity of drugs?].
AB  - In the submitted review the authors discuss the nephrotoxicity of drugs which is
      a serious danger of pharmacotherapy. Clinically it may be manifested in different
      ways from acute deterioration of renal functions to the picture of chronic renal
      insufficiency. It is particularly important to know the nephrotoxic potential of
      different drug groups and to ensure a careful stratification of patients. The
      most frequent drug groups which lead to affection of the kidneys are
      radiocontrasting substances, aminoglycoside antibiotics, non-steroid analgesics
      antiphlogistics and ACE inhibitors. With the increasing number of
      transplantations the problem of nephrotoxicity of immunosuppressives is becoming
      important. The authors analyze in each group risk factors, the pathogenesis,
      clinical picture and prognosis of damage. Special emphasis is laid on adherence
      to preventive measures and careful monitoring of the laboratory and clinical
      picture, in particular in risk groups of patients as treatment of already
      developed nephrotoxic sequelae of pharmacotherapy is frequently difficult.

PMID- 12061207
TI  - [Specific inhibitors of cyclooxygenase type 2] ].
AB  - In the submitted review the author analyzes the ratio, function and role of two
      different forms of cyclooxygenases--cyclooxygenase type 1 and cyclooxygenase type
      2--in the human organism. Special attention is devoted to specific inhibitors of
      cyclooxygenase type 2. Specific inhibition of COX-2 is associated with a lower
      incidence of undesirable reactions while the antiinflammatory and analgetic
      effect is preserved. Celecoxib and rofecoxib--the oldest representatives of drugs
      from this group were used in a number of clinical studies. The results of some of
      these studies are presented and commented.

PMID- 12061208
TI  - [Differential diagnosis of adrenal incidentalomas and the role of imaging
      methods].
AB  - In the last fifteen years the development of imaging techniques, especially the
      routine use of computed tomography (CT) and magnetic resonance imaging (MRI) lead
      to increased number of incidentally discovered adrenal masses. Facing the
      incidentalomas, it is necessary to make decisions about further management of the
      patient. This paper gives a review of diagnostic and therapeutic approaches to
      the adrenal incidentaloma, with available imaging tools and with the stress on
      the importance of particular imaging techniques.

PMID- 12061209
TI  - [Beta-blockers in the treatment of chronic heart failure].
AB  - The authors discuss in the submitted review the problem of therapeutic use of
      beta-blockers in the treatment of cardiac failure. n the introduction they
      emphasize the medical and societal consequences of this disease with emphasis on
      necessary prevention. In the subsequent part they present a review of the most
      important clinical studies (completed and under way) focused on the mentioned
      problem. In the discussion they analyze the role of the sympathetic nervous
      system in the pathogenesis of cardiac failure and the theoretical basis of the
      use of beta-blockers in its treatment. In the conclusion they present a summary
      of practical principles for the use of beta-blockers in this indication.

PMID- 12061210
TI  - [Anemia of chronic disease--standards for diagnosis and therapy. Recommendations
      of the Hematologic Section of the J.E. Purkyne Czech Medical Society].

PMID- 12061211
TI  - [The preoperative examination. Recommendations of the Czech Internal Medicine
      Section of the J.E. Purkyne Czech Medical Society].

PMID- 12061212
TI  - [Arteriovenous fistula as a complication of renal biopsy].
AB  - Renal biopsy is nowadays considered a relatively safe and routine examination
      method in nephrology. Its development was made possible by extension of
      sonography and introduction of modern automatic bioptic sets. Relatively frequent
      complications of biopsy include macrohaematuria, perirenal haematomas and AV
      fistulae. The majority of complications is unimportant from the clinical aspect.
      Some 30% fistulae do not recede spontaneously and gradual remodelling of the
      circulation near the fistula may lead to the development of complications. In the
      submitted paper the authors inform on the case of a 55-year-old woman where 24
      hours after biopsy of a renal graft a sonographically revealed arteriovenous
      fistula closed spontaneously within one month; the case of a 40-year-old woman
      where 5 days after biopsy progression of a subcapsular haematoma and
      manifestation of a fistula occurred, and a 35-year-old man who developed 6 years
      after biopsy gradually an arteriovenous fistula with uncontrollable hypertension,
      hypercirculation syndrome and functional deterioration of the transplanted
      kidney. Superselective embolization led to improvement of the circulatory
      sequelae of the vascular shunt but did not have a favourable impact on renal
      function. Analysis of hitherto assembled experience indicates that direct
      ultrasound control of biopsy is effective. Because the manifestation of possible
      complications of biopsy need not follow immediately after the operation
      ultrasound follow up of native and transplanted kidneys after biopsy is justified
      even after a longer time interval after the operation.

PMID- 12061213
TI  - [Catastrophe medicine. Historical notes].
AB  - Catastrophe medicine, which originated from military and war medicine, was
      introduced in Switzerland by the University of Basel in the 70s it was then
      adopted from other Faculties and included it in the instruction program from the
      political authority. It is a hard and difficult subject because more agreeable
      together with emergency medicine in all its aspects. Emergency medicine differs
      from catastrophe medicine in the analysis of "ideal" measures in daily practice
      in front of the necessary selection or triage, difficult task even on the ethical
      plan. With this concept, Emergency State of Crisis developed with all of is
      correlated services: political authority, police, National Fire Department, civil
      and military health, Samaritan organization.

PMID- 12061214
TI  - [Advanced technology in emergency surgery: from microsurgery to robotics].
AB  - AIMS: State-of-the-Art on clinical applications of Advanced Technologies in
      Emergency Surgery. MATERIAL AND METHODS: Evaluation of present technological
      applications in Emergency Surgery, according also to author's personal experience
      and that of his School. RESULTS: Significant improvement of cost/benefits ratio
      at medium and long term and positive social implications. DISCUSSION: The
      rational application of Advanced Technologies in Emergency Surgery is expected in
      second level Italian DEA (e.g.: Department of Emergency and Trauma of the highest
      level), natural site of main Centers for Surgical Emergencies, according to
      National and International Literature analysis. CONCLUSIONS: The advantages of
      using the most advanced technologies in Emergency Surgery from the organizing
      point of view have positive implications on University School of Medicine ambit
      for educational programs and post-graduate schools.

PMID- 12061215
TI  - [Non-toxic multinodular goitre: which surgery?].
AB  - AIM OF THE STUDY: Evaluation of total thyroidectomy, subtotal thyroidectomy and
      lobectomy in the management of multinodular non-toxic goitre. MATERIALS AND
      METHODS: 225 patients: 101 total thyroidectomies, 64 sub-total thyroidectomies,
      29 lobo-hystmectomies. Hemorrages, recurrent nerve palsies, post-operatory
      hypocalcemias, clinical and ultrasonographic relapses, undesired effects of
      ormonal therapy and hypothyroidism after partial resection (considered risk
      factor for recurrence) have been pointed out. RESULTS: All three procedures
      showed a low incidence of recurrent nerve palsy; lobectomy didn't show post
      operatory hypocalcemia, that appeared respectively in 26.6% and 23% after sub
      total and total thyroidectomy. Recurrence's percentage in patients followed-up,
      was 18.2% after lobectomy and 12.2% after sub-total thyroidectomy, but in that
      group we observed 46.9% of hypothyroidism (vs. 9.1% after lobectomy) and 8.6% of
      undesired effects of therapy. Reoperations showed inferior laringeal palsy and
      post-operatory hypocalcemia significantly more elevated. DISCUSSION: Compared to
      lobectomy, total thyroidectomy showed higher risk of hypoparathyroidism; compared
      to subtotal thyroidectomy, it showed on all occasions less incidence of
      complications. Endocrinological follow-up is easier after total thyroidectomy.
      CONCLUSIONS: According to our results, we deem the indications for lobectomy have
      to be limited to the patients having solitary nodule, undoubtedly benign, without
      familiarity or other environmental risk factor of goitre.

PMID- 12061216
TI  - [The so-called angiodysplasias of the digestive system].
AB  - The chapter on angiodysplasias of the gastrointestinal tract raises numerous,
      still problematic, issues: classification of the disorder (its clinical
      presentation and classification) its anatomo-pathological identification
      diagnosis of its nature and localization treatment of patients with acute massive
      bleeding long-term outcomes The possibility that an angiodysplasia underlies a
      bleeding event, even serious, makes this a timely topic. The exiguity of the
      lesion responsible for bleeding entails noteworthy diagnostic difficulties. By
      contrast, the relative rarity of such events, as well as of pertinent evidence in
      literature, do not allow a better understanding of the disease or, above all, its
      management. Nevertheless, it is important to bear the disorder in mind when faced
      with massive bleeding of unknown origin.

PMID- 12061217
TI  - [Biliary ileus: diagnosis and therapy].
AB  - BACKGROUND: Gallstone ileus represents 1-3% of mechanical obstructions of the
      bowel. The surgical treatment performed in urgency has a mortality rates of 10
      13% because galistone ileus is frequent in the elderly. Some diagnostic and
      therapeutic problems are debated in this paper. METHODS: 9 cases of gallstone
      ileus were analysed retrospectively in a series of 736 mechanical obstructions of
      the bowel submitted to surgery since 1969. The Authors report the clinical and
      physical data, the laboratory data and the results of the radiological procedures
      performed (plain abdominal X-ray, abdominal US, CT, MNR). The patients are
      stratified according to ASA system and the surgical treatment. The accuracy of
      the diagnostic procedures and the surgical mortality and morbidity are reported.
      RESULTS: The preoperative diagnosis was correct in 5 patients. History, clinical
      and laboratory findings are not specific. The plain abdominal X-ray was specific
      in 1/9 case, Us in 4/9, CT in 2/3, MNR in 1/1. 1 patient was included in ASA 1
      class, 3 in ASA 2 class, and 5 in ASA 3 class. Enterolithotomy alone was
      performed in 3 cases and the one stage treatment (enterolithotomy and bilio
      digestive fistula repair) in 6. No patient was submitted to two stage procedure
      because 2 of the patients submitted to enterolithotomy alone had a neoplastic
      fistula and 1 had a very high operative risk. No intraoperative mortality was
      registered. A wound infection developed in 4 patients. None of the patients had a
      recurrence of gallstone ileus. CONCLUSION: Evidence from this study supports one
      stage treatment when the diagnosis of gallstone ileus is correct because it is
      possible to delay the surgery and to perform a preoperative treatment to decrease
      the operative risk in the elderly. The correct preoperative diagnosis is often
      difficult but CT and MNR heve an high sensibility and specificity.

PMID- 12061218
TI  - Inflammatory response in open and laparoscopic cholecystectomy.
AB  - The modifications of IL-6. CRP, ceruloplasmin, alpha 1 antitrypsin, fibrinogen,
      transferrin, albumin and leukocytes counts have been evaluated after traditional
      open cholecystectomy (OC) or laparoscopic cholecystectomy (LC). Forty-two
      patients were included in this study, 20 underwent to OC and 22 underwent to LC.
      Serum samples were performed before surgery and at distance of 6, 24, 48 and 168
      hours. The results show a more significant increase in acute phase inflammatory
      response after OC compared with LC as attested by highest values of leukocytosis,
      IL-6, CRP, fibrinogen and alpha 1 antitrypsin and lower levels of albumin. In
      conclusion, after LC, the phase acute response is attenuate and it can explain
      the reduced period of convalescence of patients treated with LC.

PMID- 12061219
TI  - [Contribution to the knowledge on natural history of giant hepatic angioma].
AB  - Hepatic haemangiomas are mostly discovered by chance because of their limited
      dimensions. Their treatment is optional and very often an observing conservative
      strategy is adopted whilst a danger is foreseeing from different facts. Very
      different is the case of giant haemangiomas discovered because their bulk and
      discomfort coming from the compression exerted on near structures. In this cases
      a surgical treatment, segmentectomy or hemiepatectomy, are the current demanding
      choices. But if the volume of haemangioma is too bulky and occupies most hepatic
      parenchyma the necessary resection may be too extended and possibly dangerous.
      The two observations of the paper refer to two patients followed conservatively
      for over 20 years. In fact the volume of the haemangiomas in both patients was
      too large, the symptoms were only related to the weight of the mass and therefore
      a surgical solution was deferred to a possible worsening of the symptomatology.
      Such worsening didn't happen in the time for both the patients, demonstrating
      that the natural history of such lesion can also be very benign over many years.

PMID- 12061220
TI  - [Surgical treatment of epiphrenic diverticulum based on associated functional
      changes: report of a case].
AB  - OBJECTIVE: The authors report their experience about the surgical treatment of a
      epiphrenic diverticulum (ED) associated with motor disfunctions and
      gastroesophageal reflux. DESIGN: Report of 1 case; evaluation of effectiveness of
      the treatment. SETTING: Operative Unit of General and Thoracic Surgery,
      Department of Surgical, Anatomical and Oncological Disciplines. Policlinico,
      University of Palermo. INTERVENTIONS: Thoracotomic diverticulectomy + esophageal
      extramucosal myotomy + antireflux procedure. RESULTS: Resolution of
      syntomatology. Negative the follow up. CONCLUSIONS: ED is the epiphenomenon of
      esophageal motor disfunctions. The surgical procedure is based on their
      comprehension and on the study of this factors.

PMID- 12061221
TI  - The first-reported case of diffuse purulent peritonitis in a patient with
      retroperitoneal Hodgkin disease (etiopathogenetic hypotheses).
AB  - We report a case of purulent diffuse peritonitis in a patient who was affected by
      Hodgkin lymphoma, with no evidence of other abdominal diseases. This is a 54 y.
      old. white male who was admitted to our department with a history of asthenia,
      recurrent fever, dysphagia and abdominal pain. In the plain abdominal radiology
      pneumoperitoneum was evident. Duodenal perforation suspicion was confirmed by
      anamnesis and plain radiology which showed the presence of intra abdominal air.
      Emergency exploratory laparotomy showed a purulent diffuse peritonitis, which
      relapsed after multiple surgical toilettes and peritoneal lavage. A postoperative
      abdominal CT scan and histology of a biopsy taken during the second surgical
      operation showed a retroperitoneal Hodgkin lymphoma, which went to remission
      after chemotherapy. Considering the two simultaneous clinical manifestations
      (retroperitoneal Hodgkin lymphoma and peritonitis), we made two pathogenetic
      hypotheses: a) The retroperitoneal disease produced lymphatic stagnation and
      peritoneal transudation, which then was infected; b) The abnormal lymph nodes
      were infected and the abdominal cavity was contaminated from retroperitoneum from
      blood/lymphatic stream or by contiguity.

PMID- 12061223
TI  - [Endoscopic treatment combined with adrenaline injection and coagulation with
      argon plasma in gastroduodenal peptic ulcer bleeding].
AB  - Although endoscopic injection therapy is an effective method for bleeding peptic
      ulcers, it is associated with significant re-bleeding rate; whether the addition
      of thermal method improves the outcome is still unclear. Our previous experience
      showed that Argon Plasma Coagulation (APC) alone is not sufficient in stopping
      spurting haemorrhage, and potentially dangerous for large non bleeding visible
      vessels (NBVV). Our hypothesis was that combination of adrenaline injection (AI)
      and thermal therapy could be more efficient than thermal therapy alone for
      permanent haemostasis of active bleeding peptic ulcers, and particularly
      appropriate for NBVV treatment. From October 1998 to February 2000 we examined
      two hundred patients with upper gastrointestinal bleeding. Fifty-three patients
      with major peptic ulcer haemorrhages received combined injection therapy with
      adrenaline 1:10.000 and Argon plasma coagulation; there were 34 male and 19
      female with a mean age of 63.2 +/- 1.2 years (range 22-93). The bleeding site was
      duodenal in 30 patients, gastric in 17 patients, anastomotic in 5 patients and
      esophageal in 1 patient. Endoscopic findings were the following: active bleeding
      in 23 patients (6 spurting, 17 oozing), non bleeding visible vessels in 12
      patients and fresh adherent clots in 18 patients. Initial haemostasis was
      achieved in 52/53 patients (98.1%). Re-bleeding was observed in 5/52 cases
      (9.6%). Surgery was necessary in 3/53 patients (5.6%). Mortality was 7.5% (4
      cases). No major complications resulted from this treatment. Primary adrenaline
      injection provided initial bleeding arrest, facilitating the following
      application of APC, because of a more precise definition of the active bleeding
      site. Rates of initial hemostasis were significantly higher with combined therapy
      (injection + APC) compared to APC treatment alone. We believe that Adrenaline and
      APC combined therapy is an effective and safe method for treatment of non
      variceal gastrointestinal bleeding.

PMID- 12061222
TI  - Chronic liver herniation through a right Bochdalek hernia with acute onset in
      adulthood.
AB  - Congenital right diaphragmatic hernia of Bochdalek rarely occurs in adults and
      usually is asymptomatic. We report a right Bochdalek hernia with chronic liver
      herniation and intestinal malrotation in a 55-year old woman who presented with
      acute intestinal occlusion. The diagnosis required definitive confirmation by CT
      scan. With impending strangulation, emergency surgery through a thoracoabdominal
      approach resulted in an easy hernia repair and reduced the technical difficulties
      due to the intestinal malrotation.

PMID- 12061224
TI  - [Treatment of single hepatic metastasis from surgically treated breast carcinoma.
      (Report of a clinical case and review of the literature)].
AB  - In the natural history of the breast cancer, the liver metastatic location
      represents a clear element of an advanced stage of the disease, because it is
      often accompanied to multiple locations in the same organ and/or in different
      organs and tissues. The finding into two years after the primary intervention,
      during the ordinary follow-up, of an insulated metastasis in the 3rd hepatic
      segment in a patient operated for breast carcinoma, and the following surgical
      treatment of the metastasis, have suggested us to draft this note. The finding of
      a single metastasis in the liver in patients operated for breast carcinoma
      imposes a revaluation of the stage of sickness to highlight the contemporary
      presence of subsequent distance metastatic location; the negativity of the
      instrumental investigations performed has triggered the question about the type
      of therapeutic treatment to do to the patient. The range of therapeutic
      hypothesis spaces from the ultrasound guided mini-invasive techniques
      (alcoholization, infusion of LAK cells, use of radio frequencies), to the
      chemotherapy, so general that local one, by means of super selective
      catheterization of the hepatic artery, up to the, finally, minus usual (in these
      cases) surgical therapy. In the patient observed we have chosen the surgical
      treatment, consisting of a segmentary resection, we haven't any complication,
      neither intra- nor post-operative, and the patient was discharged in 8th day. Our
      choice of the surgical approach has bean consequence of an attentive evaluation
      so of the clinical indicators of the patient (good general conditions, bulk of
      the injury and surgical treatableness) that of the biological parameters of the
      neoplasm. The results of our experience, in line with whet indicated from the
      other AA., encourage the choice of the surgical treatment of the insulated
      hepatic metastasis from breast carcinoma, with the awareness of the concept of
      "adjuvant" that it necessarily engages in such circumstances, and, however, after
      an accurate selection of the patients.

PMID- 12061225
TI  - Seeding from early stage gallbladder carcinoma after laparoscopic
      cholecystectomy.
AB  - In the last years laparoscopic cholecystectomy has become the "gold standard
      therapy" in the treatment of symptomatic cholelitiasis, but it is necessary to
      keep into account some problems and risks that can arise from laparoscopic
      technique. One of these risks is represented surely by the disregarding of a
      gallbladder carcinoma. The authors report a case of peritoneal seeding of an
      unsuspected gallbladder carcinoma following laparoscopic cholecystectomy. The
      first histologic diagnosis was chronic ulcerous cholecystitis with adenomiosis
      but 2 months later the metastasis developed at the umbilical port site, at
      another port site and to the right lobe of the liver. Another histological
      sampling of the gallbladder specimen was performed and this time a little intra
      mucous gallbladder adenocarcinoma was found (T1 stage). While the most part of
      literature data concern advanced stage of the disease at the time of operation
      (T2, T3) only few reports regard early stage neoplasm. Therefore this risk is
      present not only in advanced stages of gallbladder carcinoma but even in cases of
      early stage cancers. After a laparoscopic cholecystectomy all specimen should be
      opened and inspected. If there is a gallbladder wall irregularity and if there
      was a bile spillage it is advisable to perform a preoperative histologic
      examination.

PMID- 12061226
TI  - Hemorrhagic cholecystitis as a likely cause of nontraumatic hemobilia in
      metachromatic leukodystrophy: report of a case.
AB  - A 17-years-old man with the juvenile form of MLD developed massive hemobilia. CT
      and US scans showed blood and clots filling the gallbladder and the biliary ways,
      with no bleeding source seen at selective angiography. Explorative laparotomy
      evidenced bleeding from a papillomatous gallbladder mucosa, resolved with
      cholecystectomy. Histologic examination with specific colorations diagnosed
      hemorrhagic cholecystitis from metachromatic leukodystrophy of the gallbladder.
      This is, to our knowing, the third case reported in Literature, and thus
      hemorrhagic cholecystitis may be considered a life-threatening complication of
      MLD to be prevented with cholecystectomy as soon as signs of gallbladder
      pathology (papillomatosis/polyposis, jaundice, abdominal pain) are suspected.

PMID- 12061227
TI  - [Remote teaching in surgery: problem-based learning, telementoring, and
      evaluation tests].
AB  - The authors propose the use of distant learning in the surgical knowledge
      teaching. The problem based learning methodology can support this new didactic
      approach. Telementoring is an interactive experimental methodology that allows
      young surgeons education by distant learning tutoring of an expert surgeon. The
      problem about assessment of efficacy and quality of computer-assisted instruction
      is to day under evaluation.

PMID- 12061228
TI  - Follicular and oocyte development in gilts of different age.
AB  - The aim of the present study was to estimate follicular and oocyte development of
      the same gilts in three phases of their reproductive life--prepuberal gilt (6
      months old), cycling gilt (9.5 months old) and primiparous sow. Follicular
      development was induced by injections of 1000 IU PMSG followed by 500 IU hCG 72 h
      later. Cumulus-oocyte-complexes (COCs) were recovered from preovulatory follicles
      of the left ovary, and follicular fluid (FF) from the right ovary always 34 h
      after hCG by endoscopy. Altogether, 19 gilts were used in the prepuberal (P) and
      cycling (C) trials and 12 of them in the primiparous trial (S). Altogether 168,
      190 and 82 follicles were aspirated from the left ovary and 106, 125 and 42 COCs
      recovered (recovery rate 60.5 +/- 26.9, 62.7 +/- 20.9 and 52.9 +/- 21.8%). The
      average number of follicles was higher in C compared to P (19.7 +/- 6.8 vs. 15.7
      +/- 6.8, p = 0.06) and to S (14.2 +/- 4.0, p < 0.05), respectively. More uniform
      expanded COCs were aspirated from prepuberal and cycling gilts as compared to
      sows (89.7 and 78.4% vs. 46.3%, p < 0.05). Furthermore, the meiotic configuration
      in oocytes differed (p < 0.05) between these groups (55.5 and 61.7% vs. 0% Telo
      1/Meta 2). Concentrations of progesterone in FF decreased (p < 0.05) from 590.0
      +/- 333.6 (P) to 249.1 +/- 72.6 (C) and 161.4 +/- 75.2 ng/ml (S). FF
      concentrations of oestradiol-17 beta were different between gilts and sows (9.3
      +/- 2.9, 21.9 +/- 10.6 and 94.0 +/- 15.9 pg/ml, p < 0.05). The
      progesterone/oestradiol ratio was 72.1, 15.2 and 4.7. Results indicate a
      different follicular and oocyte development during the investigated lifetime
      periods. Cycling gilts should preferably be used in IVF and breeding programs.
      The lower reproductive potential of primiparous sows is taken into consideration
      at breeding. Prediction of lifetime performance based on individual ovarian
      reaction of prepuberal gilts is unsuitable.

PMID- 12061229
TI  - Determination of hexachlorobenzene (HCB) in the perirenal and dorsal fatty
      tissues of pigs.
AB  - The aim of this study was to assess the suitability of the perirenal fatty tissue
      for the determination of an organochlorine pesticide. Fatty tissue samples were
      prepared by the matrix solid phase dispersion (MSPD) method, and pesticide levels
      were determined by gas chromatography on capillary column using an electron
      capture detector. Results were confirmed by gas chromatography/mass spectrometry
      (GC/MS) system. The results showed that the perirenal fatty tissue contained
      significantly higher levels of hexachlorobenzene (HCB) than the dorsal fatty
      tissue (P < 0.01). All the levels were below the criteria for maximum residue
      limits established by Croatia and the EU.

PMID- 12061230
TI  - Equid herpesvirus 1 is neurotropic in mice, but latency from which infectious
      virus can be reactivated does not occur.
AB  - Equid herpesvirus 1 (EHV-1) is the most common cause of virus-induced abortion in
      horses. After primary infection the virus becomes latent predominantly in the
      respiratory tract lymph nodes and the genome can also be detected in the
      peripheral nervous system. The role of mouse as a feasible model for the
      establishment of latency and reactivation of EHV-1 was investigated.
      Intracerebral and intranasal infections of 3- and 17-day-old mice were made and
      virus replication was confirmed by virus isolation and detected by indirect
      immunofluorescence (IIF) in brain. For reactivation studies, the mice were killed
      8 weeks post infection and tissues were collected for cocultivation. In mice from
      both age groups, infectious virus was not detected by cocultivation. Following
      attempts to reactivate virus in vivo with corticosteroids, the viral antigen was
      detected at low levels by IIF and the expression of the gB gene by reverse
      transcription polymerase chain reaction (RT-PCR) in brain, trigeminal ganglia,
      olfactory lobe, lung and spleen. Virus was also detected by IIF following
      incubation of tissue explants in the growth medium containing pokeweed mitogen
      (PWM). These results show the limitations of the mouse model for investigating
      EHV-1 latency and highlights the issue of 'ineffective reactivation' of virus.

PMID- 12061231
TI  - Occurrence of anthrax in Kars district, Turkey.
AB  - The aims of the study were to determine the prevalence of anthrax by
      bacteriologic methods in cattle and sheep between January 2000 and September 2001
      and to determine the distribution of this zoonotic disease in humans in Kars
      district, Turkey. Bacillus anthracis was isolated and identified in 34 out of 38
      (91%) cattle and 11 out of 17 (64%) sheep samples obtained from organs suspected
      of anthrax. The records of the Governmental Health Branch showed that 89 cases of
      cutaneous anthrax were diagnosed in humans during the study periods in the same
      district.

PMID- 12061232
TI  - Comparison of echocardiography and gated equilibrium radionuclide
      ventriculography in the measurements of left ventricular systolic function
      parameters in healthy dogs.
AB  - Left ventricular systolic function was assessed in 12 healthy dogs with
      equilibrium radionuclide ventriculography. The results of the analysis were
      compared to traditional echocardiographic measurements. Left ventricular internal
      dimensions and volume were measured at the time of end-systole and end-diastole.
      Ejection fraction--one of the most informative parameters of cardiac function-
      was calculated in each animal. Values (e.g. EDD, ESD, EDV, ESV) measured by the
      scintigraphic method were significantly (Student's t-test, p < 0.05) higher than
      the data obtained by echocardiography. Ejection fraction (EF) was the only
      parameter that did not differ significantly when comparing the two imaging
      techniques. The difference between the results of parallel measurements was in
      inverse ratio to the size of the heart.

PMID- 12061233
TI  - Canine tumour suppressor gene p53 mutation in a case of anaplastic carcinoma of
      the intestine.
AB  - Tumours localised in the large bowel of dogs were subjected to molecular genetic
      studies. Highly conserved regions of the tumour suppressor gene p53, including
      typical tumour hot spots (codons 175, 245, 248, 249, 273 and 282), were analysed.
      A mutation CGG-->TGG (arginine-->tryptophan) was present in codon 249 in an
      anaplastic carcinoma in the caecum.

PMID- 12061234
TI  - Influence of rapeseed meal on productivity and health of broiler chicks.
AB  - Research was focussed on investigating the influence of different quantities (0,
      10, 20 and 30%) of rapeseed meal (RM), 00-cultivar Silvia on production results,
      as well as on the morphological and pathohistological changes in the internal
      organs of chicks during the course of the experiment, measured on the 21st and
      42nd days of the 42-day experiment. The experiment involved 120 chicks divided
      into four groups: a control group (C) and three experimental groups (E1-3). It
      was found that chicks in Groups C, E1 and E2 realised significantly (P < 0.05)
      higher gains than those in Group E3, both after the test period and at the end of
      the experiment. No significant differences with regard to feed conversion were
      found between groups of chicks. Throughout the experiment chicks in Groups E1-3
      were found to have a significantly (P < 0.05) heavier liver. Compared to Groups
      E1-3, Group C chicks had a significantly (P < 0.05) heavier gizzard after 21
      days, but following the finisher diet Group E3 had a significantly (P < 0.05)
      lighter gizzard. Compared with birds in Group C, those in Groups E2-3 had
      significantly heavier (P < 0.05) unevacuated intestines when fed the starter
      diet, and those in Groups E1-2 showed a similar result when fed the finisher
      diet. Chicks in Group E3 had a significantly lower grill weight than those in
      Groups C, E1 and E2, both in the first half of the experiment and at the end. The
      starter diet did not result in any differences in the quantity of abdominal fat
      among groups, but following the finisher diet Groups E2-3 showed significantly
      less abdominal fat in comparison to Groups C and E1 (P < 0.05). Group C showed a
      significantly higher carcass yield than Groups E1-3 (P < 0.05) in the first half
      of the experiment and at the end. Groups E1-3 manifested a slight to medium
      hypertrophy of thyroid epithelial tissue as well as slight thymus hypertrophy and
      slight atrophy of the cloacal bursa follicles.

PMID- 12061235
TI  - Occurrence of porcine dermatitis and nephropathy syndrome in Hungary.
AB  - In the past few years a characteristics, often fatal disease associated with
      cutaneous lesions and nephropathy has been observed in several large pig herds
      and household pig stocks of Hungary. In addition to general symptoms and slight
      fever in several cases, the disease was characterised by cutaneous lesions
      occurring mostly on the ventral part of the thorax and abdomen, on the
      extremities and ear pinnae, and in the nasal and perianal region. In the acute
      phase, circumscribed hyperaemic, confluent, crust-covered areas were seen.
      Histological examination revealed necrosis of the epithelial layer and lympho
      histiocytic vasculitis in the corium, here and there accompanied by thrombosis
      and fibrinoid degeneration. The kidneys were pale brown and harder to tear, with
      cortical petechiae in most cases. By histopathological examination, intra- and
      extracapillary glomerulonephritis accompanied by fibrinoid exudation was seen.
      Some of the renal tubules were dilated, others were atrophied, and in advanced
      cases proliferation of the intertubular connective tissue and inflammatory cell
      infiltration also occurred. Necrotic vasculitis was also observed in some cases.
      By immunohistochemical examination IgA, IgG and IgM, and in a single case C3
      belonging to the complement system were observed in the pathologically changed
      skin areas and kidneys. By polymerase chain reaction (PCR), porcine circovirus
      type 2 (PCV-2) was detected. Bacteriological and serological examinations did not
      reveal infections of aetiological importance.

PMID- 12061236
TI  - Differences between the European carp (Cyprinus carpio carpio) and the coloured
      carp (Cyprinus carpio haematopterus) in susceptibility to Thelohanellus nikolskii
      (Myxosporea) infection.
AB  - Thelohanellus nikolskii infection of the common carp (Cyprinus carpio L.) has
      been a common parasitosis in the Central European fish farms since the first
      detection of the parasite about 20 years ago. This parasite, introduced from the
      Far East, causes intensive infection on the fins of fingerlings of the carp
      subspecies cultured in Europe (European carp, Cyprinus carpio carpio). This
      infection of the common carp occurs in the Hungarian fish farms every year. Until
      the present study, this parasite had not been recorded from the fins of koi or
      coloured carp (Cyprinus carpio haematopterus), a carp of Far Eastern origin,
      which is cultured in Hungary as an ornamental fish. A recent survey conducted in
      common carp, koi and goldfish stocks demonstrated that T. nikolskii infection of
      low prevalence and intensity occurs also in koi populations, but its prevalence
      and intensity are markedly lower than in common carp kept in the same ponds. It
      is suggested that the observed differences are due to disparities in the
      susceptibility of the two carp subspecies to T. nikolskii, and that the koi is
      less susceptible to this infection. Other signs of susceptibility can also be
      observed in the European subspecies, since in 15% of the fish plasmodium
      development was arrested at an early stage. Thelohanellus nikolskii infection
      could not be demonstrated on goldfish (Carassius auratus).

PMID- 12061237
TI  - Molecular biology can differentiate morphologically indistinguishable Myxosporean
      species: Myxobolus elegans and M. hungaricus.
AB  - Two, morphologically indistinguishable myxosporean species, Myxobolus elegans
      Kashkovsky, 1966 and M. hungaricus Jaczo, 1940 were differentiated using
      molecular biological methods. Polymerase chain reaction (PCR) with primers
      specific for the family Myxobolidae was used to amplify an approximately 1600
      base pairs (bp) long fragment of the 18S ribosomal RNA gene. In restriction
      fragment length polymorphism (RFLP) study with HinfI, MspI and TaqI enzymes, the
      two parasite species were easily distinguishable. The genetic distinctness was
      also confirmed by the DNA sequence of their PCR products. Although M. elegans and
      M. hungaricus are morphologically very similar, based on the results of the PCR
      RFLP and the DNA sequences, we concluded that they are valid species.

PMID- 12061238
TI  - Dermatitis associated with Dirofilaria (Nochtiella) repens microfilariae in dogs
      from central Italy.
AB  - Pruritic dermatitis associated with Dirofilaria (Nochtiella) repens microfilariae
      in the blood was diagnosed in 22 dogs from Fermo (Central Italy). According to
      the history, previous unsuccessful treatments with corticosteroids, antibiotics,
      restricted diet, flea control, levamisole and ivermectin were recorded in 17 dogs
      (77.3%). The combined filtration tests and antigen tests, performed during the
      study, were negative for Dirofilaria immitis and Acanthocheilonema reconditum in
      each case. Dermatological lesions included erythema, papules, single or
      multifocal alopecia, eczema, lichenification, crusting and nodules. All dogs had
      pruritus. Concurrent babesiosis was diagnosed in the blood smears of each case
      (100%), and 60% of the dogs were found to be carriers of canine granulocytic
      ehrlichiosis (CGE). Three dogs (13.6%) were positive for leishmaniosis.
      Eradication of the concurrent infections followed by specific macro- and
      microfilaricide treatment led to complete recovery from the dermatological
      syndrome. The main conclusion of the study is that D. repens infection can be
      more pathogenic than is currently considered, and it is apparently an
      opportunistic disease with serious dermatological consequences.

PMID- 12061239
TI  - Effect of GnRH and its antagonist (Antarelix) on LH release from cultured bovine
      anterior pituitary cells.
AB  - In the following investigations, the LH secretion of cells from pituitaries in
      heifers on days 16-18 of their oestrous cycle (n = 14) was analysed. Cells were
      dissociated with trypsin and collagenase and maintained in a static culture
      system. For the estimation of LH release, the cells were incubated with various
      concentrations of mammalian GnRH (Lutrelef) for 6 h. To determine the action of
      Antarelix (GnRH antagonist), the cells were preincubated for 1 h with
      concentrations of 10(-5) or 10(-4) M Antarelix followed by 10(-6) M GnRH
      coincubation for a further 6 h. At the end of each incubation, the medium was
      collected for LH analysis. Parallel, intracellular LH was qualitatively detected
      by immunocytochemistry. Changes in the intensity of LH staining within the cells
      in dependence of different GnRH concentrations were not observed, but a
      significant increase LH secretion in pituitary cells was measured at 10(-6) M
      GnRH. Antarelix had no effect on basal LH secretion at concentrations of 10(-4)
      and 10(-5) M. After coincubation of pituitary cells with Antarelix and GnRH,
      Antarelix blocked the GnRH-stimulated LH secretion with a maximal effect of 10(
      4) M, but the staining of immunoreactive intracellular LH was detected at
      approximately the same level compared to the pituitary cells treated with
      exogenous GnRH alone. These data demonstrate that Antarelix is effective in
      influencing the GnRH-stimulated LH secretion of pituitary cells in vitro. After
      administration of Antarelix in vivo, the GnRH-stimulated LH secretion of cultured
      pituitary cells was not inhibited.

PMID- 12061240
TI  - Zinc supplementation decreases total thyroid hormone concentration in small
      ruminants.
AB  - The effect of dietary zinc (Zn) supplementation on plasma Zn and serum thyroid
      hormones was evaluated in healthy male Merino lambs and Angora goats. A total of
      12 lambs and 12 goats were divided into two equal groups as control and Zn groups
      in separate experiments. The lambs and goats of the control groups were fed basal
      rations alone. The Zn contents of these rations prepared for lambs and goats were
      40 mg/kg and 35 mg/kg in dry matter (DM), respectively. Both species of animals
      in the Zn groups were fed a basal ration supplemented with zinc sulphate adjusted
      to 250 mg Zn/kg diet in DM. The feeding trial lasted for 12 weeks in lambs and 8
      weeks in goats. Blood samples were taken from the jugular vein at 4-week
      intervals. Both animal species in the Zn groups had higher plasma Zn values than
      the controls throughout the experimental period, except in the 4th week in goats.
      However, the levels of serum total thyroxine (T4) and triiodothyronine (T3) were
      lower in the lambs and goats of the Zn groups, except in the 4th week, as
      compared to those in the controls. Moreover, serum total thyroid hormone levels
      of the goats were higher at the 4th week than at the 8th week. Although there was
      a decrease in the levels of free thyroxine and triiodothyronine of both small
      ruminant species in the Zn groups when compared to the controls, these
      alterations were not statistically significant. These results may show that zinc
      supplementation to the diet at this dose reduces total thyroid hormone levels in
      small ruminants but does not yet impair the euthyroid status of the organism.

PMID- 12061241
TI  - [Limit of root canal obturation by gutta percha compaction technique in single
      rooted teeth. Clinical data apropos of 168 canals].
AB  - After the introduction of the lateral compactage of gutta percha in endodontic
      clinic of OdontoStomatology Institute of Dakar in 1995; the immediate evaluation
      of the quality and the limit of the canal obturation due to a prospective study
      on 157 monoradicular teeth so be 168 canals (11 supplementary canals) has shown
      that 75% of canals are of type I of Vertucci and that the apical limit of
      security is reached within 80.25% of cases. The manual step back canal
      preparation (79.17%) and the technique of canal obturation by lateral compactage
      of gutta percha [(64.88%); Apical limit of security: 59.52%] permit to obtain a
      densities (95.83%) and homogeneous (79.57%) canal obturation. The indication of
      gutta percha compactage on monoradicular teeth (hermetic and tridimensional root
      canal filling) must avail to apical curved roots of lateral incisive, the use of
      adapted instruments in case of canines (31 mm) and apical stop cone on necrotic
      pulp teeth.

PMID- 12061242
TI  - [Efficacy of scaling and root planing in the treatment of periodontal pockets].
AB  - Our study, who's aim was to evaluate the efficacy of scaling in pocket's
      treatment, has been realised on 78 sites, selected on 12 patients who presented a
      periodontitis. The results shown an improvement of the gingival status and a
      decrease of pocket's depth on 84.61% of treated sites; this results indicate that
      scaling and root planning procedure, well realised, is an efficient and useful
      method in periodontal treatments.

PMID- 12061244
TI  - Management of impacted third molars among Nigerian dentists.
AB  - Seventy-five Nigerian dentists were interviewed on their approach to the
      management of impacted third molars. The mean age of the dentists was 34.8 years,
      with a male/female ratio of 3.4:1. Most of the female dentists were found in the
      training institutions (p = 0.005). More than half of the dentists (58.7%)
      practiced in institutions with dental schools (training institutions), majority
      preferred the buccal approach (92%), and all the dentists (100%) preferred third
      molar disimpaction under local analgesia. Most dentists (88%) prescribe
      antibiotics following third molar surgery. Fifty dentists (66.7%) routinely
      reviewed all patients postoperatively while 12 dentists (16%) were of the opinion
      that all impacted third molars should be extracted. Only 21 dentists (28%) were
      aware of any protocol on the management of impacted teeth. More dentists in the
      training institutions performed third molar surgery less frequently than dentists
      in other hospitals (p = 0.07) who tend to employ chisels/mallet for bone removal
      (p = 0.0004). The need for continuing education and the formulation of guidelines
      in order to assist dentists to make informed decisions is emphasised. This will
      help conserve scarce resources and enhance the operation of the newly introduced
      National Health Insurance Scheme.

PMID- 12061243
TI  - [Injuries of permanent incisors: epidemiology and management in a public health
      clinic in Dakar].
AB  - This prospective study done in a dental care center in a near suburb of Dakar
      during a period between January 1999 and December 2000, bas shown that permanent
      incisors traumatism's frequency is about 10.30% (61 teeth) which come within
      common values of the literature; and a sex ratio of 2.25. These traumatisms
      concern central maxillary incisors (75.41%) on patients less than 20 years old;
      falls, violence and road accidents are the major etiology. The consulting time
      limit is quite disadvantaged to preserve pulp vitality and dental re-implant in
      case of recent traumatisms. 53.33% of old dental traumatisms are observed to
      patients between 20 and 40 years old. And overall 80.76% of endodontic treatments
      realised in this case were not finished. The control of pain and anxiety would
      ease the emergency treatment. The information's of patients about significance of
      the consulting time limit, their motivation on differed dental treatments and/or
      endodontic treatments, as well the post traumatic watch would improve the
      management and the prognostic by setting of a referenced dental care units.

PMID- 12061245
TI  - [Horizontal root fracture in a maxillary central incisor: restoration after
      endodontic treatment].
AB  - It's about the conservation of a central maxillary incisive, presenting an
      horizontal radicular fracture, without communication with the intra-oral cavity
      and after endodontic treatment and fasten down. The post-therapeutic control
      after 6 months has shown a cicatricial cal formed.

PMID- 12061246
TI  - [Short term evaluation of 24 cases of endodontic retreatment].
AB  - This study shows and evaluates the quality of the new root canal filling and
      periapical healing about 24 cases of endodontic retreatment, equivalent of 7.76%
      of endodontic treatments done at the clinic. The main consultation purposes were
      pain (54.17%) and pre-prosthetic control (40.90%) on these patients. 75% of teeth
      were treated in a single session attempt to 45 minutes. The root canal filling is
      performed in 91.65% of cases, with the safe apical limit reached in 88.13% and
      94.11% per apical healing toward a short term results.

PMID- 12061247
TI  - [Hygiene and methods of decontamination, disinfection and sterilization in dental
      offices in Yaounde].
AB  - Hygiene and asepsis of the dental office depend on medical ethics and legal
      obligation. The survey done with the participation of 33 practitioners over the
      42 practicing in Yaounde allows apprehending the reality of the daily hygiene.
      The ways of cleaning, decontamination, disinfection or of sterilization of the
      premises, the dental equipment and instruments, hand-washing, disposable
      materials and the vaccination protection of the practitioners were analyzed. The
      cleaning of the floor and door mats is daily (100%); disinfection is done daily
      in 83% of the departments in all of the centers. The cleaning and disinfection of
      the dental chair is daily and is done using soap (23%) and/or bleaching-water
      (56%). Cleaning or disinfection of the suction machine is done with soap (24%) or
      with bleaching-water (47%). The hand-pieces and the turbines are cleaned and/or
      disinfected after each usage in (94%) with alcohol (17%) or with bleaching-water
      (32%) and sterilized with a heat sterilizer (45%), an autoclave(40%) or cold
      disinfected(15%). The frequency of the treatment of the instruments is well
      respected (83%). Nevertheless the products used are very varied and are not
      always used in the prescribed order. Hand-washing is systematic after each
      patient; 50% of the practitioners use soap bars or powered soap and 50% use an
      antiseptic or a disinfectant solutions. With the regard to the vaccination, only
      3 practitioners were properly vaccinated against hepatitis B, tetanus,
      diphtheria, poliomyelitis and tuberculosis. With regard to the protection of the
      practitioners, 72% do not wear caps, 56% do not wear eyeglasses, 40% do not wear
      masks, 95% do not use rubber dams, 56% do not disinfect the radiographic films
      and 37% do not disinfect the impressions; the habitual attire consists of a smock
      worn over street clothes (78%) and street shoes (90%). The debris is burnt in 35%
      of the centers. Better knowledge of the different stages (cleaning,
      decontamination, disinfection or sterilization and the products used, absolute
      respect of the disposable materials, optimal vaccination protection and the
      elaboration of the correct procedures written and posted up in the different
      departments are fundamental points for quality treatment. As a matter of fact,
      negligence and ignorance of the rules of hygiene and asepsis should not be part
      and parcel of the therapeutic hazard in the dental department.

PMID- 12061248
TI  - [In vitro study of chlorhexidine resistance in subgingival bacteria].
AB  - Chlorhexidine is an antibacterial agent of the bisguanide family. It's the most
      effectual molecule of all antiseptics for oral use. Because of its so frequent
      use, we have elaborated a protocol in order to estimate the resistance of the sub
      gingival flora bacteria to its actions. We have determined the minimal inhibitory
      concentration of the different observed bacteria species and, have from that
      stage, progressively increased the concentration at a rate of 5 micrograms/ml.
      The obtained results show that the bacteria can undergo structural and/or
      biochemical alterations to adapt to more significant concentrations.

PMID- 12061249
TI  - [The place of radiography in endodontic treatment carried out in general practice
      in Dakar].
AB  - An investigation conducted over dental surgeons of 52 dental offices in Dakar and
      it's near suburb (40 from private sector and 12 from public and quasi-public) has
      shown that the use of retro-alveolar radiography during endodontic treatment was
      not systematic, due to the price of retro-alveolar film, waste of time and
      relative facility of the endodontic treatment of monoradicular teeth. The
      preparatory negative is favored (32.70%) particularly by private dental surgeons,
      who use two retro-alveolar films for endodontic treatment: pre and post operative
      radiography (30%). The immediate post operator control is executed only in case
      of post-operator pains by public and quasi-public dental surgeons (16.67%) with
      one retro-alveolar film on average for the endodontic treatment; at term any
      radiographic control is done. Three retro-alveolar films per endodontic treatment
      were exceptionally used (9.61%) and offset incidences (15%) are not much used as
      well as support-films (angulators). The retro-alveolar radiography is still a
      reliable guide for a clinical success in endodontic treatment with a minimum of
      three retro-alveolar films and offset incidences.

PMID- 12061250
TI  - Formulation approaches for orally administered poorly soluble drugs.
AB  - Despite having pharmacodynamic or target activity, many drugs fail in the drug
      development process due to poor bioavailability, and presently marketed
      conventional dosage forms of poorly soluble drugs employ high doses leading to
      potential toxicity. The introduction of the Biopharmaceutic Classification System
      (BCS) has provided a basis to categorize drugs based on the two major parameters
      affecting absorption, solubility and permeability. Several techniques can be
      employed to enhance the absorption and bioavailability of poorly soluble and
      poorly permeable drugs based on the BCS concept. This article is an attempt to
      summarize the development of various formulation approaches that are currently
      employed to enhance bioavailability of orally administered poorly soluble drugs.

PMID- 12061251
TI  - Synthesis and biological activity of disubstituted 4,5-polymethylenepyrazoles as
      selective cyclooxygenase-2 inhibitors.
AB  - A series of 1,3- and 2,3-disubstituted 4,5-polymethylenepyrazole derivatives were
      prepared and their inhibitory activities on cyclooxygenase-2 were evaluated.
      Among the compounds prepared, 1,3-isomer, 3-cyclohexyl-l-(4-fluorophenyl) 4,5
      trimethylenepyra-zole (5be) showed the most potent (IC50 = 0.008 microM)
      inhibitory activity with little selectivity (13-fold) on cyclooxygenase-2.

PMID- 12061252
TI  - Synthesis and pharmacological investigation of some novel 2-phenyl-3-(substituted
      methyl amino) quinazolin-4(3H)-ones as H1-receptor blockers.
AB  - A series of 2-phenyl-3-(substituted methyl amino) quinazolin-4(3H)-ones were
      synthesized from 3-amino-2-phenyl quinazolin-4(3H)-one. Their structures were
      confirmed by spectral data (IR, NMR, and MS) and the purity was ascertained by
      microanalysis. When tested for H1-receptor blocking activity on isolated guinea
      pig ileum all the test compounds inhibited histamine induced contraction whereas
      the compounds 1 (IC50 0.59 x 10(3) ng/ml) and 5 (IC50 0.49 x 10(3) ng/ml) were
      found to be two fold potent when compared to standard chlorpheniramine maleate.
      These compounds show less sedation (compound 1 shows 4%, compound 5 shows 7%)
      than the standard (33%). Hence they could serve as prototype molecules for future
      development.

PMID- 12061253
TI  - Are PhAcOZ and Nsc suitable N alpha-protecting groups for protease-catalysed
      peptide synthesis?
AB  - Protecting groups are necessary chemical tools in peptide synthesis. In protease
      catalysed peptide synthesis they exert influence both on enzyme-substrate binding
      and on solubility. In this study, we have investigated the usability of various
      PhAcOZ- and Nsc-protected amino acids for protease-catalysed peptide synthesis.
      PhAcOZ-protected peptides were obtained in high yields using papain and
      thermolysin. In contrast to this, Nsc, as a base-labile alpha-amino protecting
      group, is not suitable for biocatalytic synthesis under the conditions employed.

PMID- 12061254
TI  - Development and validation of a HPLC method for the determination of cetirizine
      in pharmaceutical dosage forms.
AB  - A rapid, simple and accurate HPLC method is described for the assay of cetirizine
      in commercial dosage forms. Methanol was found to be a suitable extraction
      solvent for tablets and for preparing solutions from drops and oral liquids. The
      samples were chromatographed on a Nova-Pak C18 column and UV detected at 227 nm.
      The elution was achieved isocratically with a mobile phase of 0.067 M phosphate
      buffer pH 3.40/acetonitrile (1:1, v/v). Ketotifen was applied as an internal
      standard. The method was validated for linearity, precision, accuracy and limit
      of detection. The recovery (mean +/- SD) for tablets was 100.88% +/- 0.8967, for
      drops 100.35% +/- 0.4062 and for solutions 101.20% +/- 1.1698.

PMID- 12061255
TI  - Application of 1,3-dibromo-5,5-dimethylhydantoin (DBH) instead of bromine gas or
      bromine water decolorization for drug identification according to PH. EUR.
      Analytical methods of pharmacopoeias with DBH in respect to environmental and
      economical concern, Part 14.
AB  - PH. EUR. 2002 identifies biotin, flucytosine, polysorbate 80 and sorbic acid
      using the decolorization of bromine water. These tests can be better performed
      with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in combination of the reaction with
      fluorescein sodium resp. sodium bromide. Also fluorescein sodium PH. EUR. Suppl
      2002 can be identified with DBH.

PMID- 12061256
TI  - Evaluation of the release profiles of flavonoids from topical formulations of the
      crude extract of the leaves of Dodonea viscosa (Sapindaceae).
AB  - Quercetin and isorhamnetin are found in adequately large concentrations in the
      plant Dodonea viscosa (Sapindaceae). Plants that contain flavonoids are effective
      in the topical treatment of skin or mucous membrane inflammation. In this study,
      the release profiles of quercetin and isorhamnetin from hydrophilic, amphiphilic
      and lipophilic creams of the crude extract of Dodonea viscosa were determined
      using a multilayer membrane system. The results revealed that the hydrophilic
      cream provided the highest rate of release of both flavonoids while there was
      practically no release from the lipophilic cream. The hydrophilic cream may,
      therefore, serve most in delivering flavonoids to a diseased skin.

PMID- 12061257
TI  - Aqueous ethanolic extract of St. John's wort (Hypericum perforatum L.) induces
      growth inhibition and apoptosis in human malignant cells in vitro.
AB  - Extracts of Hypericum perforatum (St. John's wort) are widely and effectively
      used in the treatment of mild to moderate depression. In addition, hypericin, a
      component of Hypericum p. extracts, exhibits light-dependent phototoxic
      properties and can be used in phototherapy. We therefore investigated the
      cytotoxic activity of two total Hypericum p. extracts, namely from fresh and
      dried plants in the dark and after exposure to 7.5 J/cm2 white light illumination
      and compared it with the effect of hypericin on K562, U937, LN229 glioblastoma
      cell lines and normal human astrocytes. The chemical toxicity of non-illuminated
      Hypericum p. extracts in the cells tested is low as expressed by a LC50 between
      1.9-4.1 mg/ml, which corresponds to 10.3-17.3 microM hypericin and 114.4-190.7
      microM hyperforin after 48 h treatment. Hypericum p. extracts induced dose
      dependent growth arrest of human malignant cells in the absence of illumination
      with GI50 values between 0.43-1.77 mg/ml (2.3-9.7 microM hypericin, 26.1-106.7
      microM hyperforin) for the fresh plant extract and 0.59-3.03 mg/ml (2.5-12.8
      microM hypericin, 24.2-124.7 microM hyperforin) for the dried extract. The growth
      inhibitory effect of fresh Hypericum p. extract was more pronounced in leukemia
      cell lines K562 and U937, the GI50 concentrations being about 7-fold lower than
      the corresponding LC50 for the cell lines K562 and U937, but almost the same as
      the LC50 for LN229 and NHA cells. GI50 (microgram/ml) for tumor cell lines K562
      and U937 (432 and 799) established after 48 h differed significantly (p < 0.05)
      from those of LN229 and normal human astrocytes (1767 and 2900). The light
      exposed extracts were more toxic, their LC50 and GI50 values were reduced to
      values corresponding to LC50 concentration of 3.7-7.4 microM and a GI50 of 1.3
      3.5 microM for phototoxic hypericin. After exposure to light, there was a
      significant difference (p = 0.006) between the GI50 of glioblastoma LN229 cells
      (582 micrograms/ml) and normal human astrocytes (1050 micrograms/ml).
      Morphological examination by light microscopy and phosphaditylserine exposure on
      the outer plasma membrane investigated by Annexin V-binding with flow cytometry
      after 24 h confirmed that Hypericum p. extracts caused apoptosis of treated cells
      without exposure to light. Hypericum p. extracts derived from fresh herbs and
      from dried herbs which differ in their levels of phloroglucinols (hyperforin and
      adhyperforin) were compared. The hyperforin content of fresh St. John's wort
      extract exceeded that of dried plant extract by 47% and the GI50 values of fresh
      plant extract were 73%, 77% and 58% of those established for dried extract in the
      three malignant cell lines K562, U937 and LN229 in the dark (p < 0.05). Under
      white light (7.5 J/cm2), both extracts exerted comparable growth inhibitory and
      apoptosis inducing effects due to the phototoxicity of hypericin, the
      corresponding concentrations of which were in the range of 1.3-3.5 microM. The
      data reported in this study suggest that illumination is not essential for the
      growth inhibitory and apoptotic effects of Hypericum p. extracts, but light
      activation potentiates them. Furthermore, the constituent hyperforin is at least
      partly responsible for these effects in the dark.

PMID- 12061258
TI  - Studies on the signal cascade mechanism mediating the cardioprotective actions of
      bradykinin.
AB  - The cardioprotective involvement of bradykinin was evaluated using the ACE
      inhibitor, lisinopril, and the APP inhibitor, 2-mercaptoethanol alone and in
      combination in rats with experimental myocardial infarction. The signal cascade
      mechanism mediating the cardioprotective actions of bradykinin was evaluated by
      administering aspirin and methylene blue prior to lisinopril and 2
      mercaptoethanol combined treatment. Myocardial infarction was produced by
      occlusion of the left anterior descending coronary artery for 30 min followed by
      4 h of reperfusion. Infarct size was measured by the TTC stain method. Serum free
      radical levels were estimated by the method developed by Yagi. A lead II
      electrocardiogram was monitored throughout the experiment. With the combined
      inhibition of both the enzymes ACE and APP, a better cardioprotection was
      observed. The observed cardioprotection was decreased with the prior
      administration of aspirin and methylene blue. The results suggest the
      cardioprotective role of bradykinin during experimental myocardial infarction.
      The results are further suggesting the involvement of both prostaglandins and
      nitric oxide pathways in the cardioprotective actions of bradykinin.

PMID- 12061259
TI  - Protective effect of Oxadin on experimental Yersinia enterocolitica infection in
      rats.
AB  - The effect of Oxadin (a new Bulgarian antimicrobial chemotherapeutic agent) on
      some parameters of non-specific immune response was investigated in a rat model
      of infection. After mimicking natural Yersinia enterocolitica systemic infection
      the number and functional activity of blood leucocytes and peritoneal macrophages
      were compared between groups of animals treated with Oxadin before and after
      infection. A significant immunostimulating effect of Oxadin was found in both
      experimental groups but was better expressed when administered before Yersinia
      infection. Bactericidal response of peritoneal macrophages (killing ability) and
      phagocytic activity of polymorphonuclear leucocytes from animals treated with
      Oxadin and thereafter infected with Yersinia enterocolitica were significantly
      activated during the first week of study. These findings correlated with the
      enhanced number of both types of phagocytic cells and the higher glycolytic
      activity of peritoneal macrophages.

PMID- 12061260
TI  - Two new components from Serratula strangulata Iljin.
AB  - From the alcoholic extract of the whole plants of Serratula strangulata, two new
      compounds have been isolated and their structures established by spetroscopic
      methods as strangusin-A (1) and strangusin-B (2).

PMID- 12061261
TI  - Terpenes from Juniperus przewalskii and their antitumor activities.
AB  - Two new diterpenes were isolated from Juniperus przewalskii, together with 17
      known terpense. Their structures were elucidated by spectroscopic methods (IR,
      MS, 1H, 13C and 2DNMR). In addition, 3 alpha-hinokiol (3) and 3 alpha
      hydroxymannol (9) exhibited effective antitumor activities to cervical carcinoma
      (HeLa) and human ovarian carcinoma (HO-8910) cell lines.

PMID- 12061262
TI  - [1-Aryl-isochromanes with fluoxetine-like structure].

PMID- 12061263
TI  - Enalapril maleate polymorphs: instability of form II in a tablet formulation.

PMID- 12061264
TI  - Cytotoxic activity of physalins and related compounds against HeLa cells.

PMID- 12061265
TI  - Cytotoxic constituents from Exostema mexicanum and Artemisia afra, two
      traditionally used plant remedies.

PMID- 12061266
TI  - Lens and cataract research of the 20th century: a review of results, errors and
      misunderstandings.
AB  - Lens and cataract research from a clinical, biophysical, biological and mainly
      biochemical point of view has a long tradition. Already since the beginning of
      the 20th century research relating to the chemical composition and metabolism of
      the lens was conducted. With these analyses an attempt was made to understand the
      existence and maintenance of lens transparency and the mechanisms leading to lens
      opacities. Around the middle of the century the stationary analyses measuring the
      content of certain substances in the lens were more and more replaced by the
      search for dynamic metabolic processes responsible for lens growth, maintenance
      of transparency and possibly active participation in lens function (such as
      accommodation). Also the disturbances as a result of ageing or the formation of
      lens opacities have been investigated and resulted partially in the elucidation
      of reaction chains, leading from a trigger to the formation of a cataract. Lens
      biochemistry is no longer a closed book to us, but there are still many question
      marks. Why were we not able to solve more problems around lens and cataract? The
      research effort with a remarkable financial input and a great number of
      scientists worldwide during the second half of the century does not correspond to
      the results obtained. There must be something wrong with our strategy, our
      interpretation of the results or even both. We would like to stress some points
      which might be regarded as errors or misunderstandings in the lens research
      community, thus preventing a better outcome of the enormous investment of work
      and money. A great disadvantage is the missing cooperation between clinicians and
      epidemiologists on one hand and basic lens researchers on the other. Especially
      the ignorance of basic researchers regarding the clinical problems of the lens
      and of cataracts might be to blame for several 'errors and misunderstandings'. It
      is not even so long ago since the slitlamp microscope examination of animals
      belonged to the essential standard methods of a lens research team. Another
      disadvantage still is the use of the general diagnosis 'cataract' by the
      clinicians without further classification of the topography of the opacification,
      which supports the concept that all cataracts have the same trigger mechanism.
      But most regrettable is the fact that many clinicians have never been really
      interested in basic research of the lens, in cataract pathogenesis and
      epidemiology of risk factors or in testing the efficacy of cataract-preventing
      medication. Their main goal was cataract surgery. On the basis of the success of
      the cataract surgery at the present time clinicians have even developed the
      opinion that lens and cataract research is no longer necessary to overcome
      cataract blindness. But as we all know this refers only to highly industrialized
      countries; millions of cataract-blind people are still without such help and a
      change of this condition is not in sight. In our opinion lens and cataract
      research is still necessary and it will be more successful if we bear in mind the
      mostly unintentional errors of the 20th century but keep them out of our daily
      practice.

PMID- 12061267
TI  - Evaluation of blue-light hazards from various light sources.
AB  - Visible light of short wavelength (blue light) may cause a photochemical injury
      to the retina, called photoretinitis or blue-light hazard. In this study, various
      light sources were evaluated for blue-light hazard. These sources include the
      sun, the arc associated with arc welding and plasma cutting, molten steel, iron
      and glass, the interior of furnaces, the arc or envelope of discharge lamps, the
      filament or envelope of incandescent lamps, the envelope of fluorescent lamps and
      light-emitting diodes. The spectral radiance of each light source was measured,
      and blue-light effective radiance and the corresponding permissible exposure time
      per day were calculated in accordance with the ACGIH (American Conference of
      Governmental Industrial Hygienists) standard. The sun, arc welding, plasma
      cutting and the arc of discharge lamps were found to have extremely high
      effective radiances with corresponding permissible exposure times of only 0.6-40
      s, suggesting that viewing these light sources is very hazardous to the retina.
      Other light sources were found to have low effective radiances under the study
      conditions and would pose no hazard, at least for short exposure times.

PMID- 12061268
TI  - Experimental evidence for interactive effects of chronic UV irradiation and
      nutritional deficiencies in the lens.
AB  - The eye lens is subjected to many risk factors over time, which contribute to
      changes in its transparency, finally leading in combination to cataract
      development. Ultra violet (UV) radiation is regarded as one of the widespread
      risk factors contributing to cataract formation, for example in combination with
      nutritional deficiencies. Both factors possibly contribute to the high number of
      cataracts in the sunbelt region of the world. In this study, two essential
      nutritional factors were investigated in Brown Norway rats, zinc and vitamin E
      deficiencies, alone and in combination with UV-A and UV-B irradiation. Young
      female Brown Norway rats were put on a special diet for 10 weeks, either highly
      deficient in Zinc or in vitamin E. The diet was otherwise identical to the
      control diet. Two weeks after putting the animals on the diet, UV irradiation was
      started in some of the groups with mydriatic pupils with 3 irradiation sessions
      per week (UV-A 1 J/cm2; UV-B 0.2 J/cm2). Irradiation was continued until the end
      of the diet treatment period. Body weight and food consumption were established
      at weekly intervals, as well as slitlamp microscopy to monitor changes in
      anterior eye segment morphology. In addition changes in transparency of the
      cornea and lens have been monitored and evaluated with a Scheimpflug camera
      (Topcon SL-45) at baseline, and after 4 and 8 weeks of irradiation. After
      sacrifice of the animals, the lens wet weight as well as the activity of
      superoxide dismutase (SOD) were determined. Zinc deficiency alone led to an
      almost complete arrest of body weight increase. In the cornea, UV-A in
      combination with zinc or vitamin E deficiency did not have any interactive
      effects. The combination of UV-B and zinc deficiency showed subtractive instead
      of additive effects on corneal transparency and neovascularization. In the lens
      both deficiencies positively interacted with UV-A and UV-B by increasing the
      density of the capsular and cortical layers. The lens fresh weight was
      significantly lower in zinc-deficient animals additionally irradiated with UV-A
      or UV-B. The activity of SOD was significantly lower in the lenses of zinc- or
      vitamin E-deficient animals additionally irradiated with UV-B. The experiments
      presented clearly demonstrate that dietary zinc and vitamin E deficiencies do
      interact with UV radiation damage in the cornea and lens of Brown Norway rats.

PMID- 12061269
TI  - Risk factors for nuclear lens opacification: the Reykjavik Eye Study.
AB  - PURPOSE: The purpose of this study is to examine risk factors for nuclear lens
      opacification in citizens of Reykjavik. METHODS: 1,045 persons, 583 females and
      462 males aged 50 years and older, were randomly sampled and underwent a detailed
      eye examination and answered a questionnaire. In all Scheimpflug photography of
      the anterior eye segment was done including the lens as well as retroilluminated
      photography of the lens. These photographs were used for the diagnosis of lens
      opacification. The data was analyzed using a logistic regression model. RESULTS:
      An increased risk for all grades of nuclear opacifications was found with ageing
      (OR = 1.228, 95% CI = 1.192-1.264, p = 0.000), cigarette smoking for more than 20
      pack/years (OR = 2.521, 95% CI = 1.521-4.125, p = 0.000) and pipe or cigar
      smoking (OR = 2.478, 95% CI = 1.200-5.116, p = 0.014). Outdoor exposure, cortical
      lens opacification grade II and III and computer usage were not found to be
      linked to higher risk of nuclear opacification. No correlation was found between
      nuclear opacification and the consumption of vitamins, herring, sardines and
      shrimps, cod-liver oil or plant oil, nor were iris color, hyperopia, systemic
      steroid use, cardiovascular disease, diabetes, glaucoma and pseudoexfoliation
      found to have a significant effect. CONCLUSIONS: Ageing is a major risk factor
      for nuclear lens opacification, and smoking is a major modifiable risk factor.
      Cortical and nuclear lens opacifications do not share the same modifiable risk
      factors.

PMID- 12061270
TI  - Environmental temperature and cataract progression in experimental rat cataract
      models.
AB  - PURPOSE: To clarify whether or not ambient temperature relates to cataract
      development or the progression of cataract formation. MATERIALS AND METHODS: 36
      Brown Norway rats were divided into two groups, a high-temperature (35 +/- 2
      degrees C, H = high) breeding group and a regular-temperature (24 +/- 2 degrees
      C, L = low) group. Each group was further divided into an experimentally induced
      diabetic cataract subgroup (50 mg/kg streptozotocin, DM), an ultraviolet B
      exposure-induced cataract subgroup (200 mJ/cm2, UV), and a normal control
      subgroup (C = control). Slit-lamp microscopy and an anterior image analysis
      system (EAS-1000) were used to evaluate lens changes. RESULTS: Both the HC and
      HUV groups in the 35 degrees C conditions showed higher light scattering than
      that of the 24 degrees C conditions (LC and LUV) 3 weeks after the start of the
      experiment. Nine weeks after the start of the experiment, all the rats of the UV
      subgroups (HUV and LUV) developed anterior subcapsular cataract. The temperature
      did not have much influence on the progression of the UV-B-induced cataract. From
      18 days after the start of the experiment, the HC subgroup showed a wider light
      scattering area than the LC. An increase in abnormal nuclear scattering light in
      the crystalline lens of group HC was found in 9 weeks after the start of the
      experiment, and at the end of the experiment (78 weeks later), dense abnormal
      nuclear light scattering was found including the prenuclear area. In contrast,
      the HDM group in the 35 degrees C conditions showed slower cataract progression
      than that of the LDM group at 24 degrees C room temperature. CONCLUSIONS:
      Although further experiments are necessary before we can draw any conclusions
      about temperature and nuclear changes, paying attention to the effects of
      temperature on the lens is worthwhile.

PMID- 12061271
TI  - Morphological differences between lens fibers in albino and pigmented rats.
AB  - The purpose of this study was to investigate the morphological characteristics of
      lens fibers in albino and pigmented rats by scanning electron microscopy. In
      addition to the ubiquitous interdigitating edge protrusions many ball-and-socket
      junctions were found on the lateral surfaces of lens fibers in pigmented rats.
      Notable differences in density, shape and size between superficial and deep
      cortical layers were observed. Especially, in the intermediate equatorial cortex
      large ball-and-socket junctions were found. In contrast, only few and small ball
      and-socket junctions were observed in albino rats and many ruptures of lens fiber
      membranes were present in the anterior, superficial and intermediate equatorial
      cortex. The present observations show that different strains of rats have a
      different morphology of lens fibers. In view of a postulated role of ball-and
      socket junctions in calcium homeostasis in the lens this may account for
      differences in cataractogenesis between albino and pigmented rats.

PMID- 12061272
TI  - Heterogeneity of ascorbate free radical reductase in the human lens.
AB  - The soluble ascorbate free radical (AFR) reductases in the human lens were
      separated into many isoforms in the range of pI 5-7 by native isoelectric
      focusing. In the two-dimensional gel electrophoresis, however, two main proteins
      with molecular weights of 20-25 kD were commonly identified to each isoform. The
      observed heterogeneity of the human lens AFR reductase is very similar to those
      reported for beta- and gamma-crystallins in aged and cataractous human lenses.
      From these results, it is suggested that some of the isoforms of the lens AFR
      reductase, especially the more acidic isoforms, may be formed by
      posttranslational modifications.

PMID- 12061273
TI  - The effect of modification of alpha-crystallin by prednisolone-21-hemisuccinate
      and fructose 6-phosphate on chaperone activity.
AB  - The major lenticular protein alpha-crystallin has chaperone activity. With
      increasing age this chaperone function is compromised. Diabetes and
      glucocorticoid therapy are risk factors for cataract and are associated with
      raised sugar and glucocorticoid levels, respectively. These molecules react with
      proteins. Long-lived lenticular proteins are particularly susceptible to such
      attack. To investigate this possibility we carried out incubations of alpha
      crystallin with fructose 6-phosphate and prednisolone-21-hemisuccinate and
      investigated the effect of modification on chaperone ability. Fructose 6
      phosphate and prednisolone-21-hemisuccinate compromised chaperone activity as
      measured by the beta L-crystallin thermal aggregation assay. Tryptophan
      fluorescence provided evidence that the structure of alpha-crystallin had been
      modified by both compounds.

PMID- 12061274
TI  - Steroid-induced cataract: other than in the whole animal system, in the lens
      culture system, androgens, estrogens and progestins as well as glucocorticoids
      produce a loss of transparency of the lens.
AB  - PURPOSE: To investigate the mechanism of glucocorticoid-induced cataract
      formation, the lenses of chick embryos were cultured with androgen, estrogen and
      mineralocorticoid as well as glucocorticoids. The incidence of loss of
      transparency induced by these steroids in the culture system and the whole body
      system was compared. METHODS: In the culture system, clear lenses obtained from
      16-day-old chick embryos were treated with various concentrations of steroid
      hormones for 48 h at 37 degrees C in a humidified atmosphere containing 5% CO2.
      In the whole body system, these steroids dissolved in 5% acetone in water were
      administered to 15-day-old embryos and the lenses were isolated and visually
      classified on day 17. RESULTS: When 0.25 mumol of steroids were administered to
      15-day-old chick embryos, only biologically active glucocorticoids such as
      hydrocortisone and prednisolone could cause cataract. Dexamethasone is
      approximately 25-fold stronger than hydrocortisone and prednisolone.
      Methyltestosterone as an androgen, estradiol and ethinylestradiol as estrogen,
      progesterone and 19-nor-ethisterone as progestin did not induce cataract
      formation. In the whole body system, the cataracts were caused with a dependence
      on the biological activity of glucocorticoids. However, other than in the whole
      body system, when the isolated chick lenses were cultured in the dishes, they
      could become opaque in the presence of testosterone, estradiol and aldosterone as
      well as dexamethasone and hydrocortisone at a similar dose (over 3 x 10(-5) M).
      CONCLUSION: These results demonstrate that the loss of transparency of cultured
      lens can be induced independently from biological activities of steroids.
      Glucocorticoids have various physiological and pharmacological activities in the
      living system. We assume that the steroid-induced cataract is one of the adverse
      effects caused by synergic biological activities of glucocorticoids.

PMID- 12061275
TI  - Water diffusion in the rabbit lens in vivo.
AB  - PURPOSE: To examine water diffusion in the crystalline lens and sugar cataracts
      in the rabbits in vivo. MATERIALS AND METHODS: Water self-diffusion in the lens
      cortices of alloxan-diabetic and galactosemic rabbits was examined with magnetic
      resonance imaging (MRI). The animals were positioned in a 4.7-tesla animal system
      in conjunction with a 1-inch surface coil for the eye. Diffusion-weighted MRI was
      conducted using a pulsed-gradient spin-echo sequence with a gradient strength of
      0-6 Gs/cm in the primary and secondary coordinates. Other MRI parameters included
      TR (repetition time)/TE (echo time) = 2,000/10 ms, a field of view of 4 cm, and a
      256 x 128 matrix. RESULTS: There appeared an increase in water relaxation
      resulting in an increase of % (equatorial cortex depth)/(lens long axis) from 18
      in the lenses of normal rabbits to 30.4 and 39.9 in the lenses of galactosemic
      and diabetic rabbits, respectively. In addition, water diffusion changed in the
      lens of the diabetic rabbit with an increasing intracellular fluidity along the
      long axis of the cortical fibers, for example, the diffusion coefficient changed
      from a normal of 0.48 to 0.96 x 10(-5) cm2 s-1 in the lens of the diabetic
      rabbit. These results showed altered water mobility due to subcellular
      disturbances occurring before any apparent lens opacities. Further, there also
      was an increase in the water diffusivity in the aqueous humor from a normal of
      1.77 to 2.67 x 10(-5) cm2 s-1 in the galactosemic rabbit eye suggesting an
      increase in either free water proportion or thermal convection. CONCLUSIONS:
      Resistance to water self-diffusion appeared to relate to lens fiber orientation
      and intracellular protein order. Diffusion imaging therefore can be used to
      examine water self-diffusion to detect early osmotic alteration of lens fibers.

PMID- 12061277
TI  - Studies on ultraviolet radiation and health effects: ocular exposure to
      ultraviolet radiation.
AB  - A wide variety of studies were conducted over the last 10 years to more carefully
      determine the exposure to ultraviolet (UV) radiation in the natural environment,
      which are especially concerned with the UV exposure to the eye. Careful
      measurements of global UV radiation and personal exposure were performed. A
      mannequin head model was developed that monitors the UV radiation to different
      locations on the face including at the eye. The effectiveness of hat and glasses
      and/or sunglasses was studied. Furthermore, models of estimating UV exposure were
      tested in field trials with schoolchildren, and the results were applied to the
      participants of epidemiological studies. In this article, these studies are
      briefly reviewed.

PMID- 12061276
TI  - A review of the epidemiologic evidence linking ultraviolet radiation and
      cataracts.
AB  - BACKGROUND/AIMS: Cataract is the most common cause of blindness in the world and
      there are currently no strategies to prevent it. The aim of this paper is to
      review the epidemiologic evidence linking ultraviolet (UV) radiation and
      cataract. METHODS: Published epidemiologic research articles on UV and cataract
      were reviewed against the epidemiologic criteria for causality: biological
      plausibility, strength of the association, specificity, experimental evidence,
      temporal sequence of events, dose-response relationship, and consistency.
      RESULTS: The majority of the 22 epidemiologic studies reviewed met most of the
      epidemiologic criteria for causality and support an association between UV-B and
      the development of cortical cataract and perhaps posterior subcapsular cataract.
      CONCLUSIONS: The epidemiologic data justify the implementation of public health
      campaigns to raise public awareness of the risk of cortical cataract due to
      ocular UV-B exposure. Future researchers should be careful to avoid potential
      bias by measuring personal ocular UV exposure and by quantifying cataract
      carefully.

PMID- 12061278
TI  - Geometrical gradients in the distribution of temperature and absorbed ultraviolet
      radiation in ocular tissues.
AB  - The geographical variations in the incidence of age-related ocular changes such
      as presbyopia and cataracts and diseases such as pterygium and droplet
      keratopathies have led to theories pointing to sunlight, ultraviolet radiation
      (UVR) exposure and ambient temperature as potential etiological factors. Some
      epidemiological evidence also points to an association of age-related macular
      degeneration to sunlight exposure. The actual distribution of sunlight exposure
      and the determination of temperature variations of different tissues within the
      anterior segment of the eye are difficult to assess. Of greatest importance are
      the geometrical factors that influence selective UVR exposures to different
      segments of the lens, cornea and retina. Studies show that the temperature of the
      lens and cornea varies by several degrees depending upon climate, and that the
      incidence of nuclear cataract incidence is greater in areas of higher ambient
      temperature (i.e., in the tropics). Likewise, sunlight exposure to local areas of
      the cornea, lens and retina varies greatly in different environments. However,
      epidemiological studies of the influence of environmental UVR in the development
      of cataract, pterygium, droplet keratopathies and age-related macular
      degeneration have produced surprisingly inconsistent findings. The lack of
      consistent results is seen to be due largely to either incomplete or erroneous
      estimates of outdoor UV exposure dose. Geometrical factors dominate the
      determination of UVR exposure of the eye. The degree of lid opening limits ocular
      exposure to rays entering at angles near the horizon. Clouds redistribute
      overhead UVR to the horizon sky. Mountains, trees and building shield the eye
      from direct sky exposure. Most ground surfaces reflect little UVR. The result is
      that highest UVR exposure occurs during light overcast where the horizon is
      visible and ground surface reflection is high. By contrast, exposure in a high
      mountain valley (lower ambient temperature) with green foliage results in a much
      lower ocular dose. Other findings of these studies show that retinal exposure to
      light and UVR in daylight occurs largely in the superior retina.

PMID- 12061279
TI  - High prevalence of nuclear cataract in the population of tropical and subtropical
      areas.
AB  - The authors have conducted cataract epidemiological studies in four climatically
      and racially different places and compared the data. The survey places were Noto
      and Amami in Japan, Reykjavik in Iceland, and Singapore. The evaluation and
      grading of lens opacities were done using graphic analysis of Scheimpflug and
      retro-illumination images. The prevalence of nuclear opacity was extremely high
      in the Singapore group, followed by Amami. The main type of lens opacity was
      nuclear in the Singapore group and cortical in the Noto and Icelandic groups. The
      characteristic lens opacity in Amami was in between the above two groups. No
      significant difference was seen in the prevalence of nuclear opacity between
      males and females in any of the groups. Although the common factors of the living
      conditions in the subjects with a high prevalence of nuclear opacity appear to be
      high UV exposure and high ambient temperature, future investigations should be
      made to disclose the possible cause.

PMID- 12061280
TI  - Toxicity of ultraviolet radiation exposure to the lens expressed by maximum
      tolerable dose.
AB  - The maximum tolerable dose (MTD2.3:16) for avoidance of cataract on exposure to
      ultraviolet radiation (UVR)-300 nm in the rat was here estimated at 3.65 kJ/m2.
      Sprague-Dawley rats were unilaterally exposed to UVR in the 300 nm wavelength
      region. One week after the exposure, the intensity of forward light scattering
      was measured. Toxicity for continuous response events can be estimated with MTD.
      Current safety standards for avoidance of cataract after exposure to UVR are
      based on a binary response event. It has, however, recently been shown that UVR
      induced cataract is a continuous dose-dependent event. MTD provides a
      statistically well-defined criterion of toxicity for continuous response events.

PMID- 12061281
TI  - Assessment of ocular exposure to visible light for population studies.
AB  - We have developed an empirical model with which to estimate the ocular exposure
      in the visible wavelength band. It incorporates aspects of personal behavior,
      geographic location, and season, which have been developed from population-based
      data. As presented herein, the model is strictly valid only for the northern
      hemisphere, although we discuss how it may be generalized. In conjunction with
      job history interviews, this model allows the estimate of cumulative exposures
      from age 30 in our population-based study. We present data on average annual
      exposure by age, gender, race, education, and reported photophobia. There is a
      statistically significant difference between males and females, with females
      having lower exposures. We also found statistically different exposures among the
      races with African-Americans having slightly higher median exposures than whites.
      Exposures decrease with level of education and with reported photophobia. These
      data provide the basis for characterizing lifetime exposure for the general
      population and should permit exploration of the relationship between eye disease
      and cumulative ocular exposure to visible light.

PMID- 12061282
TI  - The effects of protective eyewear on glare and crystalline lens transparency.
AB  - PURPOSE: Sunglasses have generally been used to protect against glare. Various
      kinds of sunglasses which correspond to the visual environment are on the market
      (e.g. for driving, fishing, skiing, etc.). As for the spectral transmission
      factor of sunglasses, the differences that occur in user's eyes with aging have
      not been fully considered. We investigated the relationship between different
      levels of crystalline lens transparence and the effects of glare protection using
      two kinds of filters. SUBJECTS AND METHODS: A Tri-Blocker filter (TB) and general
      driving filter (ActiveDrive, ADR) were used. The TB absorbs three spectral
      wavelengths (below 400 nm, blue light, 575 nm) and can be transparent for other
      visible light. The ADR reduces the light below 650 nm. TB and ADR transmit 52.5
      and 29.0% of the visible light, respectively. Twenty-five normal volunteers with
      transparent lenses (n = 48 eyes, aged from 22 to 68 years) and 10 cortical
      cataract patients (n = 18 eyes, aged from 48 to 71 years) were selected. The
      visual acuity of all subjects was 1.0 or better with the best correction.
      Contrast sensitivity function (CSF) was measured in four simulated light
      conditions (daylight, daylight with peripheral glare, twilight, twilight with
      central glare) by MCT8000 (Vistech). The light scattering intensity of the
      crystalline lens was measured by EAS-1000 (Nidek). RESULTS: The TB improved the
      CSF of the elderly volunteers under daylight conditions and of 1 of the cataract
      patients under all conditions. In the younger group, the CSF did not change under
      daylight conditions and deteriorated under twilight conditions. Although the ADR
      was effective for glare protection in the young volunteers, the protective
      effects of the TB were better than those of ADR for the middle-aged group.
      CONCLUSION: Sunglasses not only protect against glare but also stabilize visual
      quality under various light conditions (e.g. passing through a tunnel while
      driving). Aging changes in lens transparency should be specially considered when
      developing protective eyewear.

PMID- 12061283
TI  - Medical disorders in pregnancy--the challenges ahead.

PMID- 12061284
TI  - Are maternal deaths on the ascent in Singapore? A review of maternal mortality as
      reflected by coronial casework from 1990 to 1999.
AB  - INTRODUCTION: In Singapore, published maternal mortality rates (MMR) over the
      last decade (1990 to 1999) have been so low (0.0 to 1.0 per 1000 live births and
      still births) as to imply that maternal deaths are rare to the point of being non
      existent in some years. This inference is counterintuitive, and earlier studies
      on maternal mortality, amniotic fluid embolism (AFE) and pulmonary
      thromboembolism (PTE) have also suggested otherwise. Accordingly, local trends in
      maternal mortality warrant further examination. MATERIALS AND METHODS: A
      descriptive and comparative study, comprising a clinico-pathological review of
      maternal deaths, for which autopsies were conducted by the Centre for Forensic
      Medicine, during a 10-year period from 1990 to 1999. The annual necropsy-based,
      MMR (estimated MMR), as well as the prevalence of maternal deaths during this
      time, were estimated with the aid of the relevant, published demographic data on
      live births and still births. These were compared with the corresponding rates
      calculated (calculated MMR) from raw demographic data on maternal deaths
      classified as such in the published data. RESULTS: Coronial autopsies were
      conducted on a total of 51 cases of maternal death, of which 33, 17 and 1 were
      direct, indirect and fortuitous deaths, respectively. The annual, estimated MMR
      ranged from 0.4 to 1.8 per 10,000 live births and still births. The estimated MMR
      was twice as high as the calculated MMR and a statistically significant upward
      linear trend was demonstrated for the former (P = 0.046). AFE (16/51) and PTE
      (10/51) were the two most common causes of maternal death; their corresponding
      cause-specific, 10-year prevalence being 0.33 and 0.21 per 10,000 live births and
      still births, respectively. There was apparent clustering of the cases of PTE
      during the earlier part of the last decade (1990 to 1995), corresponding to a
      statistically significant, upward trend in its overall necropsy incidence during
      that time (P = 0.019). Cardiovascular and pulmonary disorders constituted the
      bulk of indirect deaths (13/17), while antenatal suicides accounted for 3 of
      these deaths (0.06 per 10,000 live births and still births). CONCLUSIONS: This
      was an upward trend in MMR, as reflected in coronial casework, over the last
      decade. It would appear that the local, estimated (direct and indirect) maternal
      mortality prevalence compares favourably with the MMR reported in developed
      countries. The apparent rate of AFE was no less than 4 times higher than that
      reported in the United Kingdom, while the maternal mortality rate from PTE was at
      least as high. Allowing for the possibility that such deaths were under-reported,
      the actual annual MMR and 10-year prevalence could be appreciably higher than the
      estimates presented here. There may well be a case for the establishment of a
      comprehensive database of maternal deaths, that is updated continually and
      contemporaneously, in Singapore.

PMID- 12061285
TI  - Pregnancy in women with idiopathic thrombocytopaenic purpura.
AB  - INTRODUCTION: Idiopathic thrombocytopaenic purpura (ITP) is a common
      haematological disorder in young women. The management of ITP in pregnancy is
      controversial, particularly with regards to the mode of delivery. To date, there
      is no systematic study of the outcome of these pregnancies in Singapore. AIM: To
      study the outcomes of pregnancies in Asian women with a proven diagnosis of ITP.
      MATERIALS AND METHODS: Retrospective study of 27 pregnancies in 18 women managed
      at the Singapore General Hospital from 1 January 1994 to 30 June 2001. RESULTS:
      The mean age of the women was 30 years (range, 20 to 41 years) and the mean
      parity was 1 (range, 0 to 3). Thrombocytopaenia (platelet count < 150 x 10(9)/L)
      occurred in 18 pregnancies (67%). There were 3 first trimester missed abortions
      (11%), 1 termination of pregnancy (4%), 1 stillbirth (4%) and 22 livebirths (81%)
      in this series. The mode of delivery was spontaneous vaginal in 14 women (64%),
      vacuum extraction in 2 women (9%), elective caesarean section in 5 women (23%)
      and emergency caesarean section in 1 woman (4%). All liveborn neonates were
      delivered in good condition at term. Neonatal thrombocytopaenia occurred in 4
      neonates (18%). Two neonates had cord platelet counts of less than 50 x 10(9)/L
      and 1 required therapy with corticosteroids and intravenous immune globulins. No
      bleeding complications occurred in any of the neonates. CONCLUSION: Our
      experience supports the increasingly prevalent practice of managing pregnancies
      in women with ITP with a conservative approach to investigations and treatment.
      Caesarean sections should be performed for obstetric indications only, given the
      rarity of bleeding complications in the offspring of these women and the lack of
      evidence to support its role in the prevention of neonatal intracranial
      haemorrhage.

PMID- 12061286
TI  - Gestational diabetes mellitus: a call for systematic tracing.
AB  - INTRODUCTION: Women with history of gestational diabetes mellitus (GDM) have up
      to 50% lifetime risk of developing frank diabetes mellitus (DM). They are an
      ideal group of patients to implement early interventional measures to halt the
      progression to diabetes. The success of any early intervention programme would
      depend largely on postpartum follow-up. We set out to study the response rate to
      postpartum oral glucose tolerance test (OGTT) and to profile the non-responders
      on 105 women who attended our Gestational Diabetes Joint Clinic (GDJC). MATERIALS
      AND METHODS: We divided these women into 3 groups according to their response to
      postpartum OGTT and compared their weights, glycaemic parameters and other
      clinical characteristics during gestation. Group A comprised non-responders or
      those who did not turn up for postpartum OGTT; group B comprised responders with
      a normal postpartum OGTT; and group C comprised responders with an abnormal
      postpartum OGTT defined as 2-hour plasma glucose equal or more than 7.8 mmol/L.
      RESULTS: The non-respondent rate to postpartum diabetes screening was 37.1%. The
      non-responders were found to be significantly heavier, with more severe
      hyperglycaemia during their pregnancy (in terms of glycosylated haemoglobin and
      results of antepartum OGTT) and had bigger babies compared to the responders with
      normal postpartum OGTT. Their features instead resembled those who had failed
      their postpartum OGTT. CONCLUSION: The group of non-responders was probably at
      similar risk of developing glucose intolerance postpartum as those who were
      tested abnormal. A more effective call and recall system and education programme
      is, therefore, needed to ensure postpartum attendance of all patients with GDM.

PMID- 12061287
TI  - Pregnancy after renal transplantation: experience in Singapore General Hospital.
AB  - INTRODUCTION: Renal transplantation offers the best hope for those women with end
      stage renal disease who wish to have children. However, pregnancy after renal
      transplantation is associated with increased maternal and fetal morbidity. The
      aim of this retrospective study was to review the outcome of pregnancy in renal
      transplant patients in Singapore General Hospital. MATERIALS AND METHODS: Forty
      two pregnancies, occurring between December 1986 and December 2000, in 25 out of
      141 renal transplant women in their reproductive age group (18 to 45 years old)
      were identified from our high-risk pregnancy record and retrospectively analysed.
      RESULTS: Thirteen (31%) pregnancies were unsuccessful; 10 abortions, 2 ectopic
      pregnancies and 1 stillbirth. The remaining 29(69%) successful pregnancies were
      complicated by maternal anaemia (65.5%), superimposed hypertension (44.8%),
      premature rupture of membranes (27.6%), urinary (17.2%) and lower genital tract
      (13.8%) infections, abnormal glucose tolerance test (13.8%), premature delivery
      (44.8%), low-birth-weight babies (44.8%), small-for-gestational-age babies
      (20.7%) and intrauterine growth restriction (20.7%). There were no documented
      cases of multiple pregnancies, congenital anomalies or deterioration of renal
      function. The outcome of pregnancy was not statistically influenced by
      preconception renal function and transplant-conception interval. CONCLUSIONS:
      Successful pregnancy is possible in women after renal transplantation. Such
      pregnancy is often associated with increased maternal and fetal complications and
      should be managed by a multidisciplinary approach in a tertiary centre. The
      function and survival of renal allograft was not adversely affected by pregnancy.

PMID- 12061288
TI  - Outcome of pregnancy in Asian women with systemic lupus erythematosus: experience
      of a single perinatal centre in Singapore.
AB  - OBJECTIVE: To study maternal and fetal outcomes in women with systemic lupus
      erythematosus (SLE). MATERIALS AND METHODS: Retrospective study of 27 pregnancies
      in 18 women with SLE in a single centre. RESULTS: The mean age was 30 years and
      most patients were nulliparous. Twenty-six of 27 pregnancies were in disease
      remission at the time of booking. Renal impairment was present in 7 pregnancies
      (6 women), of whom 2 were in end-stage renal disease on dialysis. Gestational
      diabetes developed in 4 pregnancies. There were 6 cases of pre-existing
      hypertension and 5 with superimposed pre-eclampsia. One woman developed
      intrapartum eclampsia. Two women had secondary antiphospholipid syndrome (APS)
      and suffered late fetal losses; in addition, they also developed SLE flares in
      the form of autoimmune haemolytic anaemia in the postpartum period. There was no
      maternal mortality. There was one termination of pregnancy for severe renal
      disease. The median gestational age at delivery was 38 weeks (range, 24 to 40
      weeks) and the mean birth weight was 3047 g; the median Apgar scores were 8 and 9
      at 1 and 5 minutes of life, respectively. There were 5 cases of intrauterine
      growth restriction (IUGR), 4 of which occurred in women with renal impairment.
      There were no cases of congenital heart block or neonatal lupus. There was a late
      fetal loss at 24 weeks in a woman with secondary APS. There were 2 preterm
      deliveries (7.4%) due to intervention for IUGR. CONCLUSION: Good pregnancy
      outcomes can be expected in women with SLE in remission. Pre-pregnancy
      counselling is crucial to achieve this. All pregnancies should still be
      considered high risk and be managed jointly between the obstetricians, the
      perinatologists and the physicians. In particular, those with renal impairment
      are at increased risk of IUGR, superimposed pre-eclampsia and preterm births. Co
      existing APS augurs a poorer prognosis for pregnancy outcome, and may present
      atypically as autoimmune haemolytic anaemia in the postpartum period.

PMID- 12061290
TI  - Management of haematologic malignancies in pregnancy.
AB  - INTRODUCTION: Malignancy complicates about 1 in 1000 pregnancies and is the
      second leading cause of death in women of reproductive age. Commonly diagnosed
      malignancies during pregnancy include breast cancer, cervical carcinoma, melanoma
      and lymphoma. Chemotherapy is usually necessary for optimal treatment, especially
      in patients with leukaemia and lymphoma. Concerns arise regarding the effects of
      imaging modalities in the pregnant cancer patients and the effects of
      chemotherapeutic agents on the developing fetus. METHODS: A Medline search of
      articles describing haematologic malignancies in pregnant patients was performed.
      Particular attention was paid to the kind of malignancy, stage of pregnancy, the
      types and side effects of chemotherapeutic agents used and the outcome of the
      pregnancy. RESULTS: There is no entirely safe cytotoxic drug or timing of
      exposure for the developing fetus. The administration of chemotherapy during
      pregnancy will not always produce a poor outcome. A pregnant cancer patient can
      also be safely and reasonably staged with imaging. Magnetic resonance imaging
      will most often be the procedure of choice as it does not use ionising radiation.
      CONCLUSIONS: The management of each pregnant patient diagnosed with a malignancy
      has to be highly individualized and involves a multidisciplinary team of medical
      personnel. The patient and her family need counselling regarding the diagnosis,
      long-term prognosis, options of termination of pregnancy, choice of
      chemotherapeutic agents and their effects on the fetus and pregnancy.

PMID- 12061289
TI  - Thyroid diseases in pregnancy.
AB  - INTRODUCTION: Changes in thyroid function in pregnancy encompass both hyper- and
      hypothyroidism. Failure to maintain euthyroidism may place both mother and foetus
      at higher risk of adverse obstetrical outcomes. This review examines the
      differences between physiological and pathological thyroid dysfunction during
      pregnancy and their management. METHODS: Data were obtained from relevant
      clinical studies and review articles listed in MEDLINE. Additional cross
      references from selected articles were identified. RESULTS: In hyperthyroidism,
      the challenge lies in differentiating gestational transient thyrotoxicosis (GTT)
      from actual pathological states during the first trimester. GTT is thought to be
      due to elevation of isoforms of human chorionic gonadotropin (hCG) which may
      exert potent thyrotrophic effects. While thionamides are safe, the lowest
      possible dose should be used together with close monitoring of maternal thyroid
      function in order to avoid over-treatment. Surgery for thyroid nodules may be
      safely performed during the second trimester. Conversely, diagnosing hypothyroid
      states, particularly subclinical hypothyroidism and postpartum thyroiditis (PPT),
      require a high index of suspicion. High levels of thyroid peroxidase antibodies
      (TPOAb) and thyroid stimulating hormone (TSH) in early pregnancy may be
      predictive of PPT and subsequent permanent hypothyroidism. Clinicians must
      recognise the need to increase thyroxine replacement as maternal hypothyroidism
      may adversely affect the IQ scores of children. The association between thyroid
      autoimmunity and recurrent abortions remain unclear. CONCLUSION: Regardless of
      the aetiology of thyroid dysfunction, the key to management lies in
      individualized therapy in close collaboration with the obstetrician.

PMID- 12061291
TI  - Management of thromboembolic disease in pregnancy.
AB  - Venous thromboembolism (VTE) is the leading cause of maternal mortality and
      morbidity in developed countries including Singapore. The physiological changes
      of pregnancy and other factors, such as maternal age, parity, obesity, operative
      delivery, general anaesthesia and congenital and acquired thrombophilia, further
      increase the risk of VTE throughout all three trimesters of pregnancy, including
      the puerperium. VTE has a wide spectrum of clinical presentations and a high
      index of clinical suspicion is vital. Clinicians should not withhold the use of
      chest X-rays and ventilation-perfusion (V/Q) lung scans in pregnancy as the
      radiation emitted is well within the safety limits to the fetus. Most treatment
      guidelines are based on studies in non-pregnant populations. Heparin is the
      preferred anticoagulant as it does not cross the placenta and therefore carries
      no teratogenic risk to the fetus. There is increasing experience and confidence
      in the use of fixed dose subcutaneous low molecular weight heparin (LMWH) which
      removes the need for cumbersome monitoring, thereby allowing outpatient
      treatment. LMWH may also have a lower risk of osteopaenic complications compared
      to unfractionated heparin. With the exception of acute phase treatment of
      pulmonary embolism, LMWH is used in all other aspects of the treatment of VTE in
      pregnancy, including thromboprophylaxis. Risk stratification of women into high
      and low risk allows judicious use of anticoagulants for thromboprophylaxis.
      Antenatal thromboprophylaxis with LMWH is reserved for high-risk women, while low
      risk women will only require such cover in the postpartum period.

PMID- 12061292
TI  - Current understanding of pre-eclampsia.
AB  - INTRODUCTION: Pre-eclampsia is associated with significant morbidity and
      mortality for mother and baby, with post partum resolution. The disorder is
      triggered by a placental pathology followed by a wide spectrum of maternal
      systemic response. However, there remains controversy in practically every aspect
      of the condition. METHODS: A Medline search and hand search of recent
      publications pertaining to the scientific basis and clinical management of pre
      eclampsia. RESULTS: With current interest in the scientific and molecular basis
      of the disease process, there has been an improved, albeit incomplete,
      understanding of the precise aetiology and pathogenesis of pre-eclampsia. Much of
      this has translated to improved clinical management strategies. The more rational
      use of various pharmacological agents, timing the delivery to optimise both the
      maternal and fetal condition, the decreasing rate of eclampsia, as well as trials
      on various screening and prophylactic strategies are testimony to this
      improvement. Despite this, many unanswered questions still remain and provide a
      challenge for both the clinician as well as the researcher. CONCLUSIONS: We
      reviewed the recent literature in order to provide a contemporary understanding
      of the basic pathogenesis of the condition as well as to highlight some basic
      strategies for clinical management. There is a clear need for more research to
      better understand the basic science behind the genesis of this condition, as well
      as to improve the level of care we offer to these women through the co-ordination
      of a multi-disciplinary team of clinicians.

PMID- 12061293
TI  - Thrombophilia in pregnancy.
AB  - INTRODUCTION: Thrombophilia refers to disorders which are associated with a
      persistent hypercoagulable state and a tendency towards thrombosis. They may be
      inherited, acquired or complex, when genetic factors interact with environmental
      influences. The objective was to review the various inherited thrombophilias and
      the antiphospholipid syndrome in relation to pregnancy-related venous
      thromboembolism and other obstetric complications. METHODS: A Medline search for
      articles highlighting thrombophilia and pregnancy-related venous thromboembolism
      and obstetric complications (pre-eclampsia, recurrent miscarriage, intrauterine
      growth restriction and placental abruption) was performed. RESULTS: The incidence
      of venous thromboembolism in pregnant Chinese women is similar to that which is
      reported for Caucasian women. Venous thromboembolism remains a major cause of
      maternal mortality worldwide as well as locally, where it ranks as the second
      commonest cause of maternal deaths (rate of maternal deaths from thromboembolism,
      0.12 per 10,000 live births and stillbirths). The major risk factors for
      thrombosis during pregnancy include thrombophilia, operative delivery, advanced
      maternal age, obesity and pre-eclampsia; these can be identified in about 70% of
      women who develop the complication during pregnancy and the puerperium. Due to
      the higher prevalence of factor V Leiden and prothrombin gene G20210A mutation in
      the Caucasian population, up to 50% of Caucasian women who develop thrombosis
      during pregnancy or the puerperium test positive for thrombophilia. Recent
      studies have also shown an association between thrombophilia and adverse
      obstetric outcomes such as recurrent miscarriage, intrauterine growth
      restriction, pre-eclampsia and placental abruption. CONCLUSION: Venous
      thromboembolism is now recognised as a multicausal and multigenic condition. This
      is particularly evident in pregnancy where multiple risk factors interact and are
      often identified in women who develop venous thrombosis. With the discovery of
      factor V Leiden and the prothrombin gene G20210A mutation, inherited
      thrombophilia can now be detected in a significant proportion of Caucasians who
      develop venous thromboembolism; however, both these mutations are rarely found in
      Asians. Identifying women at risk for venous thromboembolism and instituting
      thromboprophylaxis appropriate to the level of risk remains the key to reducing
      morbidity and mortality from the condition. Additional research into the
      intensity, type and duration of thromboprophylaxis for different levels of risk
      are required. The role of inherited thrombophilia in the pathogenesis of
      obstetric complications needs to be further defined before screening can be
      recommended for indications other than venous thromboembolism.

PMID- 12061294
TI  - Idiopathic thrombocytopenia in pregnancy.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder in which
      antiplatelet autoantibodies bind to the antigens on platelet surfaces, resulting
      in their destruction. It is one of the most common autoimmune disorders that
      physicians manage today. Although it can present itself at any age, it tends to
      occur in young women. Hence, it commonly affects women in the childbearing age
      group. It is a haematological disorder for which diagnostic and treatment
      strategies are not well defined. In the past decade, there have been attempts for
      consensus in the management of patients with ITP, resulting in practice
      guidelines being published. The management of pregnant patients with ITP,
      however, has its special problems with the added responsibility of caring for 2
      lives, the mother and her fetus. The choice of drugs is limited to those without
      teratogenic risks to the fetus and the overall aim is to prevent haemorrhage in
      both mother and fetus during the antenatal and peripartum periods. There are more
      data now to show that invasive procedures do not necessarily reduce fetal
      bleeding risk and are associated with more maternal morbidities, thus favouring
      the trend towards more conservative management.

PMID- 12061295
TI  - Rheumatic heart diseases in pregnancy.
AB  - Acute rheumatic fever and rheumatic valvular disease remain prevalent in many
      parts of the world, and are probably the most common cause of heart disease in
      pregnancy. Mitral stenosis is the most frequently encountered rheumatic valvular
      lesion. A variety of pregnancy-associated cardiovascular changes often exacerbate
      the signs and symptoms of valvular lesions. Pregnancy should not be allowed to
      proceed, if possible, in patients with uncorrected severe valvular lesions or
      mechanical heart valves requiring anticoagulation, as maternal and fetal
      morbidity and mortality are high. For those with milder disease, pregnancy is
      best undertaken after the valvular lesion has been rectified or stabilised.
      Recent advances in the management of valvular disease include the use of beta
      blockers for patients with mitral stenosis, vasodilators in those with aortic and
      mitral regurgitation, and percutaneous balloon valvuloplasty for mitral and
      aortic stenosis. Application of these therapies in the pregnant patient is as yet
      unclear, and management decision needs to be individualized, weighing the risk
      and benefit to ensure maternal survival and to promote fetal well-being.

PMID- 12061296
TI  - The course of pregnancy in a patient with nail-patella syndrome.
AB  - INTRODUCTION: The nail-patella syndrome is a rare autosomal dominant condition
      with high penetrance. Pregnancy in such a patient is rare and we believe this to
      be the first report of a live birth occurring in a patient with nail-patella
      syndrome. CLINICAL PICTURE: A 25-year-old patient presented in her first
      pregnancy with nephrotic syndrome associated with characteristic bone
      abnormalities and nail dysplasia and was later diagnosed to have nail-patella
      syndrome. In her second pregnancy, the course of her pregnancy was complicated by
      further deterioration of renal function with superimposed pre-eclampsia resulting
      in early delivery at 28 weeks. CONCLUSION: Such pregnancies should be regarded as
      high risk and managed jointly with the renal physician in a tertiary care centre
      to ensure an optimal outcome to the mother and baby.

PMID- 12061297
TI  - Four pregnancies in two patients with essential thrombocythaemia--a case report.
AB  - INTRODUCTION: We report our experience of 4 pregnancies in 2 patients who had
      essential thrombocythaemia (ET). CLINICAL PICTURE: Two patients with ET were
      managed with a variety of therapeutic approaches including the use of low-dose
      aspirin, plateletpheresis, hydroxyurea and alpha-interferon in the course of
      their 4 pregnancies. TREATMENT AND OUTCOME: One patient had 2 successful
      pregnancies despite having platelet counts in excess of 1000 x 10(9)/L
      antenatally. The second patient had an intrauterine fetal death during the third
      trimester of her first pregnancy but had a successful second pregnancy.
      CONCLUSION AND CLINICAL IMPLICATIONS: Management of ET in pregnancy is still very
      much individualized. The impact of various treatment modalities on the pregnancy
      outcome remains to be proven but a favourable pregnancy outcome is possible.

PMID- 12061298
TI  - Management of premalignant lesions of the cervix.
AB  - The screening, detection and treatment of precancer lesions of the cervix have
      resulted in a dramatic decline in the incidence of cervical cancer in many parts
      of the world. The effect is most pronounced in countries with organised
      screening. The proper management of premalignant lesions of the cervix is an
      important and integral part of any screening programme. The importance of proper
      colposcopic technique and the adherence to well-established colposcopic
      guidelines cannot be overemphasized to ensure appropriate treatment. The
      colposcope is indispensable in treatment planning as it guides the optimal amount
      of cervical tissue to be ablated or excised and the type of cone biopsy to be
      taken. Various methods of treatment involving ablative procedures and excisional
      procedures have been found to be highly efficacious and safe. The choice of
      treatment modality is very much dependent on individual preferences. However, in
      those with extensive high-grade lesions, an excisional method has the added
      advantage of detecting unsuspected microinvasive disease which can be missed if
      ablative methods are used. Although treatment for squamous intraepithelial
      neoplasia is well established, the treatment for adenocarcinoma-in-situ is more
      controversial. Newer methods of treatment are currently being developed to
      further improve on the good results achievable with present treatment modalities.

PMID- 12061299
TI  - Measuring health-related quality of life in Singapore: normal values for the
      English and Chinese SF-36 Health Survey.
AB  - OBJECTIVE: To determine norms for assessing Health-related Quality of Life
      (HRQOL) in Singapore using the Short Form 36 Health Survey (SF-36). MATERIALS AND
      METHODS: Mean SF-36 scores were calculated for 24 population subgroups
      (categorised by age, gender, ethnicity and questionnaire language) and for
      subjects with self-reported co-morbid conditions using data from a community
      based survey in Singapore. RESULTS: The English and Chinese SF-36 was completed
      by 4122 and 1381 subjects, respectively, 58% (n = 3188) of whom had self-reported
      co-morbid conditions. SF-36 scores varied in subgroups differing in age, gender
      and ethnicity. In general, subjects with self-reported co-morbid conditions had
      lower SF-36 scores than those without these conditions, the magnitude of which
      exceeded 20 points in several instances. A method for calculation of SF-36 scores
      adjusted for age, gender, ethnicity and questionnaire language is described.
      CONCLUSION: We present norms for English and Chinese SF-36 versions in Singapore
      and describe potential uses for these data in assessing HRQOL in Singapore.

PMID- 12061300
TI  - The acute presentation of pulmonary thromboembolism: a retrospective viewpoint.
AB  - INTRODUCTION: Acute pulmonary thromboembolism (PE) has been considered rare among
      Asians. We aim to describe the frequency and clinical features of this condition
      in a hospital in Singapore. Among patients admitted by the Emergency Department
      (ED), comparisons were made between those primarily diagnosed in the ED and those
      who were not. MATERIALS AND METHODS: Retrospective review of all cases of
      radiologically proven acute PE over a 20-month period. RESULTS: Sixty-two
      patients were identified. The mean age was 61.5 +/- 18.0 years with a female to
      male ratio of 1.8:1. There were more Malays compared to other races. There were
      also more Caucasians, given the proximity of the hospital to the airport and the
      inclusion of tourists. The commonest symptoms were dyspnoea and chest pain, while
      the commonest signs were tachycardia and tachypnoea. Prolonged immobilisation was
      the commonest risk factor. Electrocardiographic S1Q3T3 pattern was seen in more
      patients compared to Western studies. Cardiomegaly was the commonest chest X-ray
      finding. Thirty-two patients were identified to have a source of embolisation.
      Overall mortality rate was 21%. The ED diagnosed 36% of the cases. Alternative
      admitting diagnoses were predominantly ischaemic heart disease and pneumonia. The
      group diagnosed in the ED were notably female (P = 0.044), Caucasian (P = 0.002)
      and had prolonged immobilisation (P = 0.025) prior to the onset of PE.
      CONCLUSION: Acute PE is not as rare here as previously thought. Clinical features
      reveal more similarities than differences compared to other studies in the
      literature. We advocate a high index of suspicion for earlier diagnosis in the
      ED.

PMID- 12061302
TI  - Acute coronary syndrome--factors causing delayed presentation at the Emergency
      Department.
AB  - INTRODUCTION: The aim of the study was to identify factors that contributed to
      delays in presentation of patients with acute coronary syndrome (ACS) at the
      Emergency Department (ED). MATERIALS AND METHODS: The study population comprised
      patients presenting with the signs and symptoms of ACS at the ED of 5 government
      and restructured hospitals in Singapore from 1 April to 31 May 1999. These
      patients were interviewed with a structured questionnaire which explored patient
      demographic data, risk factors, prehospital symptomatology, timing of chest pain,
      patient response to chest pain and mode of transport to the hospital. RESULTS:
      Three hundred and two patients who made 307 visits were recruited. More than
      three-quarters of the patients presented with central or left-sided chest pain.
      Forty-seven per cent had breathlessness and 42% had sweating. The commonest day
      of presentation was Monday. It took patients a median time of 2.1 hours from
      their worst chest pain to arrive at the ED. Past history of diabetes mellitus was
      associated with a longer delay in presentation. Most of the delay was due to
      patients awaiting symptom resolution. Forty per cent came by emergency ambulances
      to hospital. CONCLUSION: Our findings identified various patient characteristics
      that contributed to delay in presentation to hospital which should be addressed
      in future education campaigns.

PMID- 12061301
TI  - Preliminary experience in radionuclide therapy of hepatocellular carcinoma using
      hepatic intra-arterial radio-conjugates.
AB  - INTRODUCTION: In a minority of the cases, resection of hepatocellular carcinoma
      (HCC) is potentially curative but local recurrence is common. Adjuvant intra
      arterial radio-conjugate therapy could potentially reduce the rate of local
      recurrence and increase disease-free and overall survival. However, in the
      majority of cases, treatment of HCC is largely palliative. A wide range of
      palliative treatment options are available and these include external radiation,
      hepatic intra-arterial chemo-embolisation, systemic chemotherapy and percutaneous
      ethanol injection. The long-term survival rate is poor. Hepatic intra-arterial
      radio-conjugate therapy provides a new and promising means of palliation.
      MATERIALS AND METHODS: We share our initial experience in the treatment of
      patients with HCC. A total of 32 patients were recruited between October 1999 and
      June 2001. Group 1 comprised 15 patients who had potentially curative resection
      of HCC who were treated with Iodine-131 (I131) lipiodol as a form of adjuvant
      therapy. Group 2 comprised 17 patients with unresectable HCC, 12 of whom were
      treated with Yttrium-90 (Y90) microspheres and 5 with Rhenium-188 (Re188)
      lipiodol. The radio-conjugates were administered via the intra-arterial route.
      RESULTS: Thirteen of the 15 patients in group 1 who were treated with I131
      lipiodol following curative resection of HCC were free of disease, 1 patient died
      and 1 patient who developed recurrence was retreated with Re188 lipiodol and was
      subsequently free of disease. The 6-month disease-free survival rate was 100% and
      the 12-month disease-free and overall survival rates were 72% and 85%,
      respectively. Of the 12 patients in group 2 who were treated with Y90
      microspheres for unresectable HCC, 6 had stable disease, 2 showed tumour
      regression and 4 died. The 6-month and 12-month survival rates were 75% and 66%,
      respectively. Of the 5 patients in group 2 who were treated with Re188 lipiodol
      for unresectable HCC, 4 had stable disease and 1 had regression of the right lobe
      tumour but progression of the left lobe tumour. CONCLUSION: Our results in the
      adjuvant treatment of patients with I131 lipiodol following curative resection of
      early HCC and in the palliative treatment of unresectable HCC using Y90
      microspheres and Re188 lipiodol are preliminary and not fully conclusive. These
      preliminary results have to be confirmed in larger groups of patients and by
      prospective, randomised, controlled trials. This study highlights the preliminary
      experience in radionuclide therapy of HCC using hepatic intra-arterial radio
      conjugates in a local context.

PMID- 12061303
TI  - A new method of evaluation of upper airway in patients with obstructive sleep
      apnoea--computer-assisted quantitative videoendoscopic analysis.
AB  - INTRODUCTION: Prospective study to quantitatively examine the static and dynamic
      changes of upper airways in patients with obstructive sleep apnoea (OSA) by
      engaging a new inexpensive clinical method which accurately evaluates the
      morphology of obstructive sites of upper airway. The aim was to minimise the
      subjective visual estimations and eliminate individual variations of the
      traditional method of nasopharyngoscopic assessment of upper airway. METHOD:
      Videoendoscopic (video-nasopharyngoscopic) examinations of upper airways of 15
      patients were carried out with a calibrator inserted through the scope and placed
      at the levels of interest. Images of upper airways during quiet respiration,
      muller manoeuvre at erect and supine positions were obtained, digitalised and
      analysed by computers to generate the actual dimensions, surface areas and hence
      collapsibility of obstructive sites of upper airways. These measurements were
      validated by comparing videoendoscopic measurements (supine, quiet respiration)
      with upper airway magnetic resonance imaging (MRI) scans. We compared the area
      measurements of 30 videoendoscopic images with MRI scans of 15 patients at two
      levels (points above uvula and epiglottis) and calculated the accuracy percentage
      by examining the differences of surface areas of these two methods of
      measurement. The MRI scan measurements were used as standard, and the differences
      were presented as an accuracy percentage. RESULTS: The accuracy for the first
      level was 89.50% and the second level was 88.15%; the mean accuracy was 88.82%.
      The mean area of MRI was 1.50 cm2 (SD = 0.69) and the mean area of
      videoendoscopic images was 1.45 cm2 (SD = 0.64), with a correlation of 0.93 and a
      P value of less than 0.001. CONCLUSION: This new cost-effective and convenient
      clinical method of upper airway evaluation enables us to quantitatively and
      accurately examine the morphology of obstructive sites of upper airway, so that
      we could further research the pathophysiology of upper airway obstruction, engage
      the most appropriate treatment and provide accurate pre and postoperative
      assessments for patients with obstructive sleep apnoea.

PMID- 12061304
TI  - Age-related macular degeneration: what's new.
AB  - INTRODUCTION: Age-related macular degeneration (AMD) is the leading cause of
      irreversible blindness in the developed western world, accounting for
      approximately 50% of all cases of registered blindness. The rising prevalence of
      this disease in Asia seems to parallel the same trend in the developed world.
      Because of the socio-economic impact of this disorder, much attention has been
      paid to elucidating the underlying pathogenic mechanisms, as well as seeking
      alternative forms of treatment. This review discusses the latest advances in AMD
      diagnosis, treatment and prophylaxis. METHODS: Medline search with emphasis on
      randomised controlled clinical trials and large case-control series. Only
      articles cited on the Index Medicus were included in this review. RESULTS: Recent
      advances in the diagnosis and treatment of AMD include conventional argon laser
      photocoagulation, photodynamic therapy (PDT), radiation therapy, surgical options
      and gene therapy. CONCLUSIONS: There have been numerous advances in the
      management of AMD and exciting new research applications have emerged. The
      introduction of exciting new modalities, such as PDT, has revolutionised the
      approach to treating CNVM and their effects on central vision. However, there has
      been no breakthrough in achieving satisfactory outcomes with the available
      techniques for treating occult neovascular lesions. As results of large
      prospective randomised clinical trials evaluating new treatment alternatives
      become available, a treatment algorithm for neovascular AMD will emerge that best
      minimises visual loss and may even result in visual improvement.

PMID- 12061305
TI  - Agreement or prediction: asking and answering the right question.
AB  - INTRODUCTION: Measuring agreement and measuring predictive ability are similar
      but distinct problems. Failure to appreciate the conceptual and practical
      differences may lead clinical researchers to give the right answer to the wrong
      question. METHODS: We illustrate the relation and difference between measuring
      agreement and predictive ability in a non-technical way. We provide a real
      example investigating the feasibility of using preoperative breast cancer tumour
      size measurements to estimate postoperative histological size. The intraclass
      correlation and R-squared are calculated to ascertain the level of agreement and
      predictive ability respectively. RESULTS: Analysis of agreement and analysis of
      predictive ability serve different purposes. The optimal solution found in terms
      of agreement may be different from that found for prediction. CONCLUSIONS: A
      careful clarification of the goal of an investigation is important. Using an
      inappropriate analysis can lead to misleading results, or to results that do not
      really answer the research question of interest.

PMID- 12061306
TI  - [Experimental gingivitis].
AB  - For the experimental gingivitis study 4 (pre)molar teeth were selected and a
      splint was made over these teeth. During toothbrushing the splint covered the
      experimental teeth. After brushing it was removed and the volunteers rinsed with
      chlorhexidine solution (1.2%) or placebo. The results showed tht chlorhexidine
      rinsing prevented almost completely the accumulation of plaque and onset of
      gingivitis. The use of the splint facilitated the compliance considerably.

PMID- 12061307
TI  - [Promotion of oral health in the elderly. Use of a videotape].
AB  - In dentistry dental health promotion of elderly people will be of growing
      interest. General health promotion is subdivided in two components: education and
      structural interventions. Stereotypes, dominating both (dental) health care
      providers and elderly people, are barriers for manifestation of elderly people's
      dental information needs. A recently developed videotape can be used as a start
      of such a structural intervention.

PMID- 12061308
TI  - [What the tooth binds onto].

PMID- 12061309
TI  - [Periodontal susceptibility].

PMID- 12061311
TI  - Caring for the children.

PMID- 12061310
TI  - [Reaction to, "Treatment advice from an acupuncturist"].

PMID- 12061312
TI  - Publications Council picks Steven Kerpen to receive Tillis Award.

PMID- 12061314
TI  - An interview with Anne Powell, RN by Anne Pogue.

PMID- 12061313
TI  - Are you ready for Culture and Nursing 202?

PMID- 12061315
TI  - FTC-Lilly settlement sheds light on e-mail privacy with patients.

PMID- 12061316
TI  - Put pen to paper.

PMID- 12061317
TI  - Nursing leadership. Interview with Lynnie Meyer, RN, MSN, by Joyce Pruitt.

PMID- 12061318
TI  - Nursing leadership. Interview with Ms. Shirley B. Powers by Nancy Cahill.

PMID- 12061319
TI  - Leadership interview with Anna Smith, Director of Nursing Department, University
      of Louisville by Kathleen M. Whelan.

PMID- 12061320
TI  - Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of
      four cases.
AB  - Karyotype analysis of bone marrow samples was performed in 20 cases of essential
      thrombocythemia (ET) at the time of diagnosis. Three patients had karyotype
      abnormalities at the time of diagnosis; trisomy 8, deletion of Y, and del(9)(q?)
      in each. The patient who had trisomy 8 at the time of diagnosis underwent myeloid
      blastic transformation in 35 months. Three patients whose karyotypes were normal
      at the time of diagnosis developed a chromosome abnormality with trisomy 8 when
      they developed myeloid blastic transformation 38, 79 and 86 months after initial
      diagnosis of ET. Two patients with blastic transformation had been treated with
      busulfan, one with hydroxyurea and one with methyl-6-[3-(2-chloroethyl)-3
      nitorosoureidol]-6-deoxy-alpha-D-glucopyranoside (MCNU). It is suggested that
      progression of the disease may have increased the incidence of trisomy 8 and the
      development of leukemic transformation.

PMID- 12061321
TI  - Development and rapid dissemination of Merkel-cell carcinomatosis following
      therapy with fludarabine and rituximab for relapsing follicular lymphoma.
AB  - This report deals with an unusual case of a patient with follicular small cleaved
      lymphocytic lymphoma who developed Merkel-cell carcinoma soon after receiving
      chemoimmunotherapy with a fludarabine-containing regimen and rituximab. The
      presentation of the Merkel-cell carcinoma in this patient was atypical because of
      the absence of dermal involvement and the very rapid clinical progression. In the
      light of recent reports which suggest a possible link between the
      immunocompromised state and the development of Merkel-cell carcinoma, the
      atypical presentation seen in this patient may indeed imply a possible link
      between the therapy given and the development of Merkel-cell carcinoma. To the
      best of our knowledge, this is the first documentation of Merkel-cell carcinoma
      appearing in a patient soon after treatment with fludarabine and/or rituximab.

PMID- 12061322
TI  - Spirituality, religiousness, and health: from research to clinical practice.

PMID- 12061323
TI  - [Symposium at the University of Witten/Herdecke, November 10-11, 2000: "Different
      paradigms in oncology--consequences for research and practice].

PMID- 12061324
TI  - [To: Pothmann R, et al: Evaluation of applied kinesiology in nutritional
      intolerance of childhood. Forsch Komplementarmed Klass Naturheilkd 2001;8:336
      344].

PMID- 12061328
TI  - High doses of riboflavin and thiamine may help in secondary prevention of
      hyperlactatemia.
AB  - Lactic acidosis is the most dramatic manifestation of nucleoside reverse
      transcriptase inhibitor (NRTI)-associated mitochondrial dysfunction. The optimal
      management of subjects who recover from an episode of lactic acidosis--or its
      milder form, symptomatic hyperlactatemia--remains unclear. Most physicians opt to
      restart NRTI-sparing regimens, but such an option may not be available for
      heavily antiretroviral-experienced patients. Therefore, there is a need to
      investigate ways to prevent the recurrence of hyperlactatemia in patients who
      require NRTI-based therapy.

PMID- 12061329
TI  - Modulation of marrow stromal osteoblast adhesion on biomimetic
      oligo[poly(ethylene glycol) fumarate] hydrogels modified with Arg-Gly-Asp
      peptides and a poly(ethyleneglycol) spacer.
AB  - Novel oligo[poly(ethylene glycol) fumarate] (OPF) hydrogels functionalized with
      cell adhesion peptides were prepared, and the effects of incorporated peptide
      density and macromolecular structure of hydrogels on attachment and morphology of
      marrow stromal cells (MSCs) were evaluated. Poly(ethylene glycol) (PEG; number
      average molecular weight of 930, 2860, and 6090) was used to synthesize OPF. A
      model peptide, Gly-Arg-Gly-Asp (GRGD), was incorporated into OPF hydrogels after
      being coupled to acrylated PEG of molecular weight 3400. The increase of
      incorporated peptide concentration enhanced MSC attachment to OPF hydrogels of
      PEG of molecular weight of 930 and 2860. However, the number of attached MSCs to
      OPF hydrogels of PEG (molecular weight 6090) remained constant regardless of the
      peptide density. The length of PEG in OPF also influenced cell attachment. When 1
      micromole peptide/g hydrogel was incorporated into the OPF hydrogels, the degree
      of cell attachment at 12 h relative to the initial seeding density was 93.9 +/-
      5.9%, 64.7 +/- 8.2%, and 9.3 +/- 6.6% for OPF hydrogels prepared with PEG of
      molecular weights of 930, 2860, and 6090, respectively. However, the crosslinking
      density of hydrogels did not significantly affect cell attachment. The
      interaction was sequence specific, in that MSC attachment to GRGD-modified
      hydrogels was competitively inhibited when cells were incubated in the presence
      of 0.5 mM soluble GRGD before cell seeding. These results suggest that we can
      modulate MSC attachment to OPF hydrogels by altering the peptide density and the
      molecular structure of OPF hydrogels.

PMID- 12061330
TI  - Development of an XTT tetrazolium salt-based assay for detection of specific
      hyperthermia sensitizers in a high-flux screening programme.
AB  - It is now possible to search for new drugs using high-throughput screening of
      chemical libraries accumulated over the past few years. To detect potential new
      hyperthermia sensitizers, we are screening for chemical inhibitors of
      thermotolerance. For the screening of a large chemical library, a rapid and
      simple assay based on the XTT-tetrazolium salt with the addition of intermediate
      electron acceptor, phenazine methosulphate (PMS) as a promoter, was developed. It
      was found that the sensitivity of the XTT/PMS assay is sufficient for assessing
      thermal cell killing and thermotolerance, although it was highly dependent on
      cell number and type. When the formazan assay system was challenged with the
      bioflavonoid drug quercetin (up to 25mm) and validated against the clonogenic
      cell survival assay, significant decreases in thermotolerant cell viability were
      observed, directly reflecting inhibition of thermotolerance. Although short-term
      assays can, in some instances, underestimate overall cell killing, the dose
      dependency of inhibition of thermotolerance by quercetin recorded in this study
      by clonogenic and XTT/PMS assays was similar. Application of the XTT/PMS assay in
      chemical library screening was highly effective in differentiating potential
      thermotolerance inhibitors from both chemicals with lack of efficacy and from
      toxic compounds. Taken together, these results show that the XTT/PMS assay, when
      carried out under careful conditions, is well suited for primary high-flux screen
      of many thousands of compounds, thus opening up new areas for discovery of
      hyperthermia sensitizers.

PMID- 12061331
TI  - Nursing has always had comfort rounds.

PMID- 12061332
TI  - Nursing has always had comfort rounds.

PMID- 12061333
TI  - Euthanasia should never be legal.

PMID- 12061334
TI  - The budget and what it means for the NHS.

PMID- 12061335
TI  - Prevalence of criminal offending by men and women with intellectual disability
      and the characteristics of offenders: implications for research and service
      development.
AB  - The investigation of the relationship between criminal offending and the presence
      of an intellectual disability (ID) is problematic for two main reasons. First,
      because of problems associated with the definition of 'ID' and secondly, because
      much criminal offending goes undetected or unreported, and studies can only
      investigate those already involved with the criminal justice process. Studies
      using IQ as a continuous variable indicate that significantly below-average
      intellectual ability is an independent predictor of future offending. Whilst
      people with ID may be over-represented in parts of the criminal justice system,
      given the intellectual and other psychosocial disadvantages which they
      experience, the level of offending behaviour in this particularly vulnerable
      group is strikingly low. The present authors propose that two broad groups of
      people can be identified. The first, broader, group is one of people for whom
      social disadvantage and mental ill health (particularly substance abuse), coupled
      with a significant intellectual impairment, are the main characteristics.
      Secondly, there is a smaller group of people, usually already known to ID
      services as service users, but for whom the process whereby what might have been
      conceptualized as 'challenging behaviour' becomes 'offending' is far from clear.
      The distinction the present authors make between challenging behaviour and
      offending is important for understanding how 'difficult' behaviour becomes
      identified as 'antisocial/criminal behaviour'. They argue that research needs to
      move from prevalence and descriptive studies to investigating the processes which
      determine movement in and out the criminal justice system. The present political
      emphasis on public protection and proposals for significantly broader mental
      health legislation raise the danger of a re-expansion of institutional models of
      care, rather than the development of multi-agency support networks. The present
      paper underscores a note of caution, particularly where choices have to be made
      between expanding institutional models on the one hand and providing more
      integrated services on the other. Over and above policy decisions, these are
      social and political choices.

PMID- 12061336
TI  - The molecular epidemiology of Echinococcus granulosus and cystic hydatid disease.
AB  - It is now generally recognized that the dog tapeworm Echinococcus granulosus, the
      cause of cystic hydatid disease, exhibits substantial genetic diversity. This
      variability has important implications for the design and development of
      vaccines, diagnostic reagents and drugs effective against this parasite. The
      paper describes various deoxyribonucleic acid-based approaches that have been
      used for accurate identification of these genetic variants and their application
      in molecular epidemiological surveys of cystic hydatid disease in different
      geographical settings.

PMID- 12061337
TI  - Right to anonymity upheld in HIV case.

PMID- 12061338
TI  - Death in Antarctica.

PMID- 12061339
TI  - Experimental rickets in rats. III. The prevention of rickets in rats by exposure
      to sunlight. 1922. J. Biol. Chem. 50, 77-81.

PMID- 12061340
TI  - Report on the International Workshop on the Biopharmaceutics Classification
      System (BCS): scientific and regulatory aspects in practice.

PMID- 12061341
TI  - [The tobacco industry in Mexico].
AB  - Smoking is presently one of the most important public health problems worldwide.
      Even though smoking is a preventable cause of morbidity and mortality, it still
      contributes importantly to the burden of disease. In Mexico, contrary to what is
      happening in other parts of the world, the smoking epidemic is in an early phase,
      as evidenced by the low number of lung cancer cases or deaths, and by the minimal
      public health efforts to control tobacco consumption. One of the most important
      advances is its recognition as a priority public health problem by public health
      workers and society in general. Effective interventions to reduce tobacco
      consumption have been launched to render the country free of tobacco. These
      public health interventions are being countered by the tobacco industry and the
      market forces that strive to preserve smoking as a life style of the population.
      The present work reviews the production means of the Mexican tobacco industry,
      particularly those of cigarettes, the market structure, and the product expansion
      in the Mexican population. This information should be useful to frame effective
      preventive measures, in the short and long term, to control this epidemic.

PMID- 12061342
TI  - [The 1964 report of the Surgeon General on health problems attributable to
      tobacco use. 1964].

PMID- 12061343
TI  - Radiography.

PMID- 12061344
TI  - [Supplement to the conservation of an entire cadaver according to W. Thiel].
AB  - Ten years after publishing the method "The preservation of complete human
      cadavers in native colours" by W Thiel an improved variant, due to the
      experiences throughout this time, will be described for the general embalming of
      corpses and a relating to the apparatus establishment for the preservation of
      brain in situ.

PMID- 12061345
TI  - Adolescent self-care: the two sides of the coin.

PMID- 12061346
TI  - Illness severity measures in neonatal intensive care.

PMID- 12061347
TI  - Indomethacin: continuous versus bolus administration.

PMID- 12061348
TI  - Is rapid surfactant analysis at birth feasible in the diagnostics of respiratory
      distress syndrome?

PMID- 12061350
TI  - Transjugular intrahepatic portosystemic shunt.

PMID- 12061349
TI  - Towards a molecular basis for intraventricular haemorrhage: nitric oxide and
      impaired cerebral autoregulation.

PMID- 12061351
TI  - Children's fluid intake during diarrhoea: a comparison of questionnaire responses
      with data from observations.
AB  - Many of the individual questions used by the World Health Organization for
      household surveys on diarrhoea management have not been systematically assessed.
      This study assessed the use of simple questions to caretakers of children to
      estimate the proportion of young children who received increased quantities of
      fluids during diarrhoeal episodes by comparing caretakers' responses with data
      obtained by direct observations. Children aged 4-35 mo (n = 215) with diarrhoea
      starting within the last 24 h were observed for 12 h. These children were
      observed for 12 h again 2 wk later, when healthy. On the following day the
      questionnaire was administered to the caretakers. The observation focused on the
      frequency of feeding episodes, including breastfeeding and the type and quantity
      of fluids consumed by the child. The same questionnaire was administered to the
      caretakers of another group of children (n = 421) with diarrhoea in the past 2
      wk. The mean number of feedings (6.0 +/- 3.8 vs 5.0 +/- 3.5), breastfeeding
      episodes (11.2 +/- 3.6 vs 8.4 +/- 3.3), breastfeeding duration (85.8 +/- 36.3 min
      vs 49.1 +/- 22.8 min), other fluid intake (345.8 +/- 309.6 ml vs 120.9 +/- 136.4
      ml) and total fluid consumption (653.9 +/- 240.4 ml vs 399.5 +/- 133.6 ml) were
      significantly higher (p < 0.0001) during diarrhoea compared with healthy periods.
      At the population level, the simple questionnaire administered to caretakers was
      found to have high agreement between the reported increase in fluid consumption
      and the actual increase in fluid intake (defined as > or = 100 ml). At the
      individual level, caretakers' questionnaire responses for detecting increased
      fluid intake were highly sensitive (84.3%), but specificity (36.4%) and agreement
      (0.22) were low. CONCLUSION: This study documents that children had higher fluid
      intake, which included both breast milk and other fluid, during acute episodes of
      diarrhoea. Further research is warranted to improve the specificity and agreement
      of caretakers' responses to simple questions regarding change in fluid intake
      during diarrhoeal episodes.

PMID- 12061352
TI  - Effectiveness and tolerability of ibuprofen-arginine versus paracetamol in
      children with fever of likely infectious origin.
AB  - The aim of this multicentre, double-blind, randomized study was to assess the
      paediatric antipyretic efficacy of a new ibuprofen formulation containing L
      arginine for gastric protection, compared with the efficacy of paracetamol. For
      this purpose 100 patients were given ibuprofen-arginine (1 drop/kg: 6.67 mg/kg)
      and 99 paracetamol (4 drops/kg: 10.65 mg/kg). The main efficacy endpoint was the
      mean change in tympanic temperature 4 h after drug intake. Twelve patients were
      excluded because of early vomiting or spitting out the medication. The resulting
      efficacy analysis population included a total of 88 patients treated with
      ibuprofen-arginine and 87 with paracetamol. Mean change in tympanic temperature
      (degrees C) showed no difference between groups (p = 0.527) but more patients in
      the ibuprofen-arginine group attained a temperature reduction greater than 2
      degrees C (p = 0.043). A total of 107 patients required antipyretic rescue
      medication, with a smaller proportion in the ibuprofen-arginine group. Although
      this was not statistically significant, a trend towards improved activity was
      observed (p = 0.100). Overall efficacy was judged from the recovery or
      improvement in 68.8% of patients in the ibuprofen-arginine group compared with
      65.5% in the paracetamol group. Nineteen patients reported adverse events, with
      vomiting being the most common complaint, but no differences were detected
      between treatments. CONCLUSION: Based on the present results, ibuprofen-arginine
      oral drops have shown to be a safe, well-tolerated and potent paediatric
      antipyretic agent. Hence, ibuprofen-arginine should be considered as an adequate
      choice for the control of paediatric fever of likely infectious aetiology.

PMID- 12061353
TI  - Early prediction of neurological sequelae or death after bacterial meningitis.
AB  - This study determined independent predictors of the occurrence of permanent
      neurological sequelae or death after childhood bacterial meningitis. Data were
      used from a large study on children (aged 1 mo to 15 y) initially presenting with
      meningeal irritation. A nested case-control study was performed on children with
      (n = 23) and without (n = 70) permanent neurological sequelae (hearing
      impairment, locomotor dysfunction, mental retardation or epilepsy) or death after
      bacterial meningitis. Predictors obtained from clinical evaluation and laboratory
      tests at presentation and during the clinical course were identified by
      multivariate logistic regression and receiver operating characteristic (ROC)
      curve analyses. The study population comprised 23 cases and 70 controls (52%
      boys, median age 2.8 y). Independent predictors for an adverse outcome after
      bacterial meningitis were male gender, atypical convulsions in history, low body
      temperature at admission and the pathogen Streptococcus pneumoniae. The area
      under the ROC curve of this prediction rule was 0.87 (95% confidence interval:
      0.78-0.96), which was not improved by adding other characteristics. A score
      including these independent predictors could classify patients into categories
      with increasing risk for an adverse outcome. CONCLUSION: Clinical characteristics
      available early in the clinical course, such as gender, atypical convulsions in
      history, low body temperature at admission and the pathogen, are predictive for
      the occurrence of permanent neurological sequelae or death after bacterial
      meningitis in childhood. The pathogen type, in particular, is the main prognostic
      determinant of childhood bacterial meningitis.

PMID- 12061354
TI  - Central airways stenosis in school-aged children: differential diagnosis from
      asthma.
AB  - This study assessed the value of spirometry and chest X-rays in the diagnosis of
      airways stenosis in the tracheal or laryngeal regions at school age. A series of
      14 patients was studied. Six of them had vascular ring anomalies, four subglottic
      stenosis, two aberrant innominate artery, one tracheal stenosis and one a
      laryngeal web. Four patients were suffering from chronic cough and ten from
      dyspnoea, noisy breathing and cough upon physical exercise. Two had had their
      symptoms since infancy and five since 3-6 y of age, whereas seven had had their
      first symptoms at school age. Nine patients had previously been suspected of
      having asthma, and five of them had been using inhaled corticosteroids, one
      inhaled sodium cromoglycate and one peroral terbutaline without any effect. The
      ratio of forced expiratory volume in 1 s (FEV1) to peak expiratory flow (PEF) was
      abnormally high in most of the patients. All six children with vascular ring
      anomalies also had an abnormal aortic configuration on a chest X-ray, and
      narrowing of the trachea was seen in two of the four with subglottic stenosis.
      Two children had both chest X-rays and spirometry values within the normal
      limits. CONCLUSION: The results show that children with stenosis in the laryngeal
      or tracheal region may not have their first symptoms until school age. Many
      patients are falsely suspected of having asthma. Simple spirometry and chest X
      rays will help the physician to make the correct diagnosis in these patients.

PMID- 12061355
TI  - Effect of two aerobic training regimens on the cardiorespiratory response of
      prepubertal boys and girls.
AB  - The aim of this study was to examine the effect of two endurance training
      regimens of varying duration and frequency on maximal oxygen uptake (VO2max) of
      prepubertal boys and girls. The subjects consisted of 84 prepubertal children,
      aged 10-11 y. Two groups, EG1 (n = 36) and EG2 (n = 20), were involved in a 13 wk
      endurance training programme (intensity: higher than 80% of maximal heart rate
      for both groups; frequency: 3 and 2 sessions per week: duration: 25-35 min and 15
      20 min per session in the target zone, for EG1 and EG2, respectively). Another
      group of 28 children served as a control group. Each subject performed a
      continuous and progressive exercise test to exhaustion on a cycle ergometer to
      evaluate VO2max before and after the 13 wk study period. The main findings of
      this study were: (i) there was no improvement in VO2max after a training
      programme with the following characteristics: 2 sessions per week with 15-20 min
      of exercise performed at an intensity higher than 80% of maximal heart rate; (ii)
      a VO2max enhancement (on average +7%) was seen only in children who participated
      in a training programme organized on the basis of three sessions per week during
      which exercise intensities higher than 80% of maximal heart rate were sustained
      for at least 25 min per session; and (iii) there was no gender difference in the
      training response. CONCLUSION: It appeared from this longitudinal study that only
      a programme with continuous activity, organized on the basis of three sessions
      per week, with 25-35 min at an intensity higher than 80% of maximal heart rate at
      each session, enhanced VO2max in prepubertal boys and girls.

PMID- 12061356
TI  - Psychomotor development in preschool children exposed to antiepileptic drugs in
      utero.
AB  - The aim of this study was to assess psychomotor development with the Griffiths'
      test in preschool children exposed to antiepileptic drugs (AED) in utero. The
      study sample consisted of 76 children exposed to AED in utero and 71 unexposed
      children. The children (exposed and unexposed) have since birth been included in
      a population-based longitudinal follow-up study of children born to women with
      meticulously treated epilepsy during pregnancy, initiated in 1985. In total, 67
      exposed and 66 unexposed children were tested with the Griffiths' test, which
      consists of 6 subsets: locomotor function, personal and social behaviour, hearing
      and speech, eye and hand coordination, performance, and practical reasoning.
      There was no significant difference in the global scores of the Griffiths' test
      between the two groups of children. Children exposed to phenytoin in utero (n =
      16) showed a significant but subtle reduction in the scores for locomotor
      development compared with the unexposed children (mean scores: 98 vs 106: 95%
      confidence interval for the difference in mean scores: -14.0 to -0.4). There was
      no such difference for the children exposed to carbamazepine in utero (n = 35).
      The exposed children had significantly fewer siblings (p < 0.01). A significant
      number of the mothers with AED treatment had no higher level of education than
      compulsory school (p < 0.01). No other differences in socioeconomic status were
      observed between the groups. CONCLUSION: The subtle delay in locomotor
      development evaluated with the Griffiths' test at 4.5-5 y of age in children
      exposed to phenytoin may indicate a subtle influence on psychomotor development,
      which may be more obvious at school age: thus, larger studies and further follow
      up are warranted.

PMID- 12061357
TI  - Score of neonatal acute physiology as a measure of illness severity in
      mechanically ventilated term babies.
AB  - The objectives of this population-based, case-control cohort study were to
      describe the use of the score of neonatal acute physiology (SNAP) as a measure of
      illness severity in mechanically ventilated term infants, to compare the SNAP
      scores of the different diagnostic groups, to assess the contribution of the
      individual SNAP items to the overall SNAP severity category, and to assess SNAP
      as a predictor of mortality and neonatal intensive care unit (NICU) resource
      utilization (length of stay (LOS) and duration of ventilation (LOV)). The study
      was carried out in Sydney and four large rural/urban health areas in New South
      Wales, Australia. The subjects--182 singleton term infants with no major
      congenital anomalies--were admitted to a tertiary NICU for mechanical
      ventilation. Highest mean (SD) SNAP scores occurred in infants ventilated for
      meconium aspiration (18 (9)), and perinatal asphyxia (17 (9)), compared with
      pulmonary hypertension (14 (6)) and respiratory distress syndrome (13 (5)). The
      individual SNAP items that contributed most to SNAP moderate and severe
      categories were blood gas items, creatinine, urine output, blood glucose, and
      seizures. Predictors of death included total SNAP score, individual SNAP items
      (urine output, pH, Oxygenation Index (OI)), 5-min Apgar, gestational age >40 wk,
      growth restriction, and ventilation for asphyxia/apnoea. SNAP alone was not a
      good predictor of NICU resource utilization (LOS, LOV) in term infants. The best
      predictors were LOV for LOS, and a combination of SNAP and the reason for
      ventilation for LOV. CONCLUSION: SNAP is a useful measure of severity of illness
      in sick term neonates admitted to a tertiary NICU. This measure can be used to
      predict neonatal morbidity and mortality, and to some extent NICU resource
      utililization.

PMID- 12061359
TI  - Continuous gastric drip versus intravenous fluids in low birthweight infants.
AB  - This multicentre randomized study compared a continuous gastric drip (CGD) with
      intravenous (i.v.) fluid administration. Healthy newborns with birthweight from
      1501 to 2000 g whose physician ordered i.v. fluids were randomized before the 2nd
      hour of life to CGD or i.v. fluids. The major outcome variable was the need for
      an i.v. line in the CGD group. Serum glucose was measured at 30 min, 1 h and
      every 6 h thereafter. Serum sodium and potassium were measured at least once
      during the first 72 h of life. Enteral feedings, feeding intolerance, number of
      venous lines and i.v. line-related complications were recorded until the
      interruption of CGD or the i.v. line. Twenty-nine infants were randomized to each
      group. The two groups were comparable in terms of birthweight and gestational
      age. Ten percent (3/29) of the infants randomized to the CGD group required i.v.
      fluids and 90% of them received electrolytes and glucose through an orogastric
      tube. The incidence of hypoglycaemia, hyponatraemia and episodes of feeding
      intolerance did not differ between the groups. CONCLUSION: Fluid administration
      by CGD reduces the need for i.v. lines without increasing the risk of
      complications.

PMID- 12061358
TI  - Reliability of the SNAP (score of neonatal acute physiology) data collection in
      mechanically ventilated term babies in New South Wales, Australia.
AB  - The aim of this population-based, case-control, cohort study was to report inter
      rater reliability between the New South Wales Neonatal Intensive Care Unit Data
      Collection (NICUS) audit nurses' collection of SNAP (OS) and a research nurse's
      SNAP data as the audit SNAP (AS). The study was carried out in Sydney and four
      large rural/urban health areas in New South Wales (NSW), Australia. The subjects-
      182 singleton term infants with no major congenital anomalies--were admitted to a
      tertiary neonatal intensive care unit (NICU) for mechanical ventilation. SNAP
      data were collected on the 182 case infants, born between 1 January and 31
      December 1996, by clinical audit officers in the nine tertiary NICUs in NSW. The
      research officer conducted an audit of the original SNAP score on all infants.
      The data were examined using Pearson's correlation coefficient, weighted kappa, a
      plot of difference in SNAP against mean SNAP and Wilcoxon's signed rank sum test.
      Pearson's correlation coefficient between the OS and AS data was 0.80. Median
      (interquartile range) SNAP was 13 (9,19) for the OS and 14 (10,20) for the AS.
      Weighted kappa was highest for highest heart rate, paO2, temperature (degrees C),
      oxygenation index, haematocrit, platelet count, lowest serum sodium, lowest blood
      glucose and seizure. In 17 (9%) infants, OS and AS differed by > or = 10, 14
      because of an original data collection error, 1 data entry error, 1 audit error
      and 1 for both data collection and data entry errors. CONCLUSION: If SNAP is to
      be incorporated into any routine NICU data collection, it should be audited
      regularly on a sample of records. It is important to standardize and adhere to
      strict definitions for parameters before the collection of SNAP data.

PMID- 12061360
TI  - Plasma guanosine 3',5'-cyclic monophosphate and severity of peri/intraventricular
      haemorrhage in the preterm newborn.
AB  - A poorly controlled cerebral circulation, caused by excessive production of
      nitric oxide, has been suggested as predisposing to peri/intraventricular
      haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation
      exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory
      nitric oxide production and severity of PIVH. In 83 consecutively admitted
      preterm neonates, nitric oxide production was assessed by measuring plasma cGMP
      at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound
      investigations were performed and haemodynamic parameters registered. The
      investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had
      mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of
      age, cGMP levels of infants with severe PIVH were significantly higher than those
      of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with
      moderate PIVHs had significantly higher cyclic cGMP levels than infants without
      PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP
      values than those of infants without PIVH. Maximal cGMP values preceded the final
      extension of PIVH in moderate and severe PIVHs. Blood pressure support was
      necessary significantly more often in infants with moderate and severe PIVH. A
      logistic regression model revealed that cGMP was significantly associated with
      PIVH, irrespective of gestational age, mean arterial pressure or severity of
      infant respiratory distress syndrome. CONCLUSION: Increased cGMP levels are
      associated with the development of PIVH. It is suggested that vasodilatory nitric
      oxide-induced impairment of cerebral autoregulation plays a role here.

PMID- 12061361
TI  - Changes in cerebral, renal and mesenteric blood flow velocity during continuous
      and bolus infusion of indomethacin.
AB  - Vasoconstriction induced by bolus injection of indomethacin reduces organ
      perfusion and has been related to the well-known side effects of indomethacin
      given for closure of the patent ductus arteriosus (PDA). The aim of the study was
      to compare the changes in cerebral, renal and mesenteric blood flow velocities
      after continuous infusion versus bolus injection of indomethacin for closure of
      the PDA. Thirty-two preterm infants (range 26-35 wk gestational age) with PDA
      were randomly assigned to receive the same amount of indomethacin either as three
      bolus injections (n = 14) or as a continuous infusion (n = 18) over 36 h. Blood
      flow velocities were measured in the internal carotid, right renal and superior
      mesenteric arteries at baseline and serially at 10, 30, 60 and 120 min and 12,
      24, 36 and 48 h after the start of indomethacin treatment. There were no
      differences in blood flow velocities between both groups at baseline. During
      continuous infusion of indomethacin there was no significant change in the
      cerebral, renal and mesenteric blood flow velocities, whereas the flow velocities
      in the infants receiving bolus injections decreased significantly during the
      first 2 h after indomethacin administration in all arteries measured. There was a
      transient, but significant reduction in urine output after bolus injection of
      indomethacin. CONCLUSION: In contrast to bolus injections, decrease of organ
      blood flow and impairment of urine output do not accompany continuous infusion of
      indomethacin over 36 h.

PMID- 12061362
TI  - Size at birth and neonatal and postneonatal mortality.
AB  - Birthweight is a crude indicator of size at birth. Some neonatologists and
      obstetricians have advocated the use of ponderal index and birthlength to
      characterize size at birth. This paper examines the associations between various
      size-at-birth indicators and neonatal and postneonatal mortality, with an
      emphasis on ponderal index and birthlength. Size at birth, gestational age and
      mortality data for about one million babies born alive in Sweden between 1987 and
      1995 were collected from the Swedish Medical Birth Registry. A multinomial logit
      regression was used to estimate conditional odds ratios. Birthlength and ponderal
      index were independently associated with neonatal and postneonatal mortality. In
      the latter period, ponderal index was only weakly associated with mortality. The
      associations were not sensitive to exclusion of cases of congenital anomalies and
      adjustment for gestational age. CONCLUSION: Birthlength is strongly associated
      with both neonatal and postneonatal mortality; ponderal index is strongly
      associated with neonatal, but weakly with postneonatal mortality. The findings
      are consistent with previous hypotheses about a transient effect of ponderal
      index and a persistent effect of birthlength.

PMID- 12061363
TI  - Main diagnosis and cause of death in a neonatal intensive care unit: do
      clinicians and pathologists agree?
AB  - AIM: To determine the agreement rates between clinical and autopsy diagnoses in a
      neonatal intensive care unit (NICU), distinguishing between the main diagnosis
      and cause of death. METHODS: Clinical and autopsy records of 75 infants who died
      in two consecutive years in the NICU (autopsy rate 42.6%) of a pediatric hospital
      in Mexico City were reviewed. RESULTS: Ninety-two percent of main clinical
      diagnoses were confirmed by autopsy. Four conditions (congenital cardiopathy,
      prematurity, specific congenital syndromes and hyaline membrane disease)
      accounted for more than two-thirds of diagnoses. However, for cause of death, the
      global agreement was only 50%. The most common conditions considered by
      clinicians (77%) and pathologists (56%) to be the causes of death were
      cardiogenic, septic or mixed shocks. Additionally, clinicians omitted 34 relevant
      conditions in 30 (40.0%) patients, and 21 of these conditions possibly played a
      role in the deaths of 17 (22.7%) patients. The most frequently omitted diagnosis
      was pneumonia, in 9 (26.5%) patients. Omissions were not related to gestational
      age, age at death, days as an inpatient, or gender. CONCLUSION: Despite a high
      agreement rate in the main diagnoses, notable imprecisions were present regarding
      cause of death and antemortem overlooking of potentially fatal conditions,
      confirming the useful role of autopsy to verify clinical diagnoses and suggesting
      that differentiation between the main diagnosis and cause of death should be
      carried out in future studies.

PMID- 12061364
TI  - Psychological well-being of orphans in Dar El Salaam, Tanzania.
AB  - Forty-one orphans whose fathers and/or mothers had died from AIDS, and were
      living in the poor suburbs of Dar Es Salaam, Tanzania, were compared with 41
      matched non-orphans from the same neighbourhoods. The subjects were given an
      arithmetic test and a semi-structured questionnaire concerning any internalizing
      problems, their attendance at school and their experiences of punishment, reward
      and hunger. The scale of internalizing problems comprised 21 items adapted from
      the Rand Mental Health and Beck Depression Inventories concerning mood,
      pessimism, somatic symptoms, sense of failure, anxiety, positive affect and
      emotional ties. Most orphans lived with aunts and uncles. Compared with non
      orphans, they were significantly less likely to be in school but those who did
      attend school had similar arithmetic scores. Significantly more orphans went to
      bed hungry. Orphans had markedly increased internalizing problems compared with
      non-orphans (p < 0.0001) and 34% reported they had contemplated suicide in the
      past year. Multiple regression analysis indicated that the independent predictors
      of internalizing problem scores were sex (females higher than males), going to
      bed hungry, no reward for good behaviour, not currently attending school, as well
      as being an orphan. CONCLUSION: The orphans not only had unmet basic needs, but
      also had markedly increased internalizing problems, thus their long-term mental
      health would be in jeopardy. There is an urgent need to expand and improve
      current intervention programmes not only to meet the basic needs but also to
      include psychosocial support, counselling services for the orphans, and training
      for their carers and teachers.

PMID- 12061365
TI  - French adolescent attitudes towards informal care for physical and emotional or
      relational problems.
AB  - The objective of this study was to determine adolescents' attitudes concerning
      the use of self-care and traditional medicines. A self-administered anonymous
      questionnaire with open-ended questions was completed by 543 adolescents aged 15
      19 y. The results showed that the most frequent self-care activity for general
      health problems, in more than three-quarters of them, was self-medication; 14% of
      them resorted to minor home treatment such as taking care of wounds, bandaging or
      massages. Instructions for use were mentioned by 69% of adolescents as a way of
      choosing self-prescribed drugs. Natural medicines were used by 32% of the girls
      and 23% of the boys, mainly herbal teas or plant-based medicines, followed by
      homoeopathy. Self-care for emotional and relational problems mainly involved
      thinking about the problem and questioning themselves about their own behaviour
      or about the way they are. They also mentioned activities such as sports, going
      out, listening to music, watching television, and trying to think about something
      else by keeping themselves occupied. Natural medicines were used by 19% of the
      girls and 13% of the boys. Plant-based medicines or herbal teas were used most
      often, followed by drugs or alcohol, with homoeopathy in third place. CONCLUSION:
      Self-care and alternative medicines were used by adolescents in this study for
      physical as well as for emotional or relational problems. Their use did not
      reflect dissatisfaction with physicians and hospital treatment or an objection to
      formal services, but rather was a choice of these approaches for their own
      specific characteristics. They were also viewed as being less harmful than
      conventional treatment.

PMID- 12061367
TI  - Hypoglycaemia and elevated urine ethylmalonic acid in a child homozygous for the
      short-chain acyl-CoA dehydrogenase 625G > A gene variation.
AB  - The aim of this case report is to call attention to short-chain acyl-CoA
      dehydrogenase (SCAD) deficiency as a possible contributory factor to
      hypoglycaemia in childhood. We report on a previously healthy 14 mo-old Danish
      boy who presented with hypoglycaemia and metabolic acidosis after a few days of
      upper airway infection. After two days on a normal diet, he recovered clinically
      and biochemically. A thorough biochemical examination did not reveal the cause of
      the hypoglycaemia. However, the excretion of ethylmalonic acid in two morning
      urine samples was moderately increased, and hence the SCAD gene was screened for
      mutations. We found the child homozygous for the G > A SCAD gene variation at
      position 625. CONCLUSION: In this patient, reduced function of the SCAD protein
      is reflected in the excretion of ethylmalonic acid, a marker of intracellular
      accumulation of butyryl-CoA and the cytotoxic butyric acid. Furthermore,
      gluconeogenesis might be compromised owing to lack of reducing equivalents from
      the oxidation of short-chain fatty acids in the fasting or stressed state, thus
      contributing to the predisposition for fasting hypoglycaemia.

PMID- 12061366
TI  - Behavioural problems in children and parenting stress associated with primary
      nocturnal enuresis in Hong Kong.
AB  - The aim of this study was to investigate the behavioural problems and parenting
      stress of enuretic children in the local Chinese community. The study recruited
      89 children with primary nocturnal enuresis (PNE) from the paediatric clinics of
      9 regional hospitals in Hong Kong, and 131 age- and gender-matched control
      children without PNE from the Student Health Centres. After adequate instruction,
      the parents completed the Child Behaviour Checklist (CBCL) and Parenting Stress
      Index (PSI). A trained interviewer interviewed the parents and children and rated
      the children on the Global Assessment of Functioning (GAF). The PNE group had
      worse overall scores in both the Problem and Competence scales of CBCL; in
      particular, they had more attention problems and aggressive behaviours, and lower
      social competence and school performance than the control group. Their parents
      demonstrated more parenting stress as shown by higher PSI scores. CONCLUSION: In
      the local Chinese population, PNE was associated with more childhood behavioural
      problems and greater parenting stress. Attention to the psychosocial functioning
      of the child and parents may be important in the management of enuresis.

PMID- 12061368
TI  - Late onset of right Bochdalek's hernia with strangulation of the omentum.
AB  - We report a case of bloody pleural effusion and infarction of the greater omentum
      caused by a non-traumatic diaphragmatic hernia with a late presentation. A 15-y
      old boy with Down's syndrome developed abdominal pain and vomiting, as well as an
      elevated serum level of C-reactive protein. Chest roentgenograms showed a right
      sided pleural effusion and computed tomography revealed a right diaphragmatic
      hernia. Barium enema confirmed the diagnosis. An operation revealed a right
      Bochdalek's hernia with strangulation of the greater omentum in the right pleural
      cavity. CONCLUSION: Diaphragmatic hernia should be considered in patients with
      pleural effusion, abdominal pain and vomiting.

PMID- 12061369
TI  - Immunogenicity and safety of a virosomal influenza vaccine in HIV-infected
      children.

PMID- 12061370
TI  - The practice parameter for the management of hyperbilirubinaemia.

PMID- 12061371
TI  - Biocavity laser will tell surgeons when to stop cutting.

PMID- 12061372
TI  - Food and Drug Administration advisory committee supports approval of antibody
      agent for the treatment of older Americans with acute myeloid leukemia.

PMID- 12061373
TI  - Radiofrequency ablation used to treat select renal and adrenal tumors.

PMID- 12061374
TI  - Maxamine enhances IL-2 in phase 3 malignant cancer.

PMID- 12061375
TI  - Long-term follow-up shows brachytherapy effective against prostate cancer.

PMID- 12061376
TI  - Familial nonmedullary thyroid cancer.
AB  - Familial nonmedullary thyroid cancer is more aggressive than sporadic
      nonmedullary thyroid cancer. It tends to affect younger patients, and the tumors
      are often multi-focal and bilateral. Histologically, 90% of these tumors are
      papillary cancers and the remaining are Hurthle cell cancers. We recommend total
      thyroidectomy to remove all the thyroid tissue, which harbors the genetic defect
      responsible for the disease (even in low-risk patients) due to the predisposition
      to develop thyroid cancer and the more aggressive nature of the disease. Careful
      exploration of the ipsilateral lymph nodes with ipsilateral central neck
      dissection is encouraged to decrease a high recurrence rate (44%). A complete
      modified radical neck dissection should be limited to a therapeutic role because
      there is no clear evidence that this procedure carries any survival benefit. We
      also recommend that patients receive radioactive iodine ablation post
      operatively, including a prophylactic dose (30 mCi) for patients with no evidence
      of residual uptake on the postoperative iodine 131 whole body scan and in low
      risk patients using any of the prognostic scoring systems. Patients should be
      placed on enough thyroid hormone to suppress thyroid-stimulating hormone (TSH) to
      approximately 0.1 mL/mL in low-risk patients and to less than 0.1 mL/mL in high
      risk patients. Focal metastatic disease in patients with familial nonmedullary
      thyroid cancer is best dealt with by surgical excision followed by radioactive
      iodine ablation when appropriate. Redifferentiation therapy has a promising role
      in patients who have radioactive iodine-resistant tumors. The value of
      prevention, early detection, and targeted gene therapy once the gene or genes
      responsible for familial non-medullary thyroid cancer have been identified cannot
      be overemphasized.

PMID- 12061377
TI  - How rational should bioethics be? The value of empirical approaches.
AB  - Rational justification of claims with empirical content calls for empirical and
      not only normative philosophical investigation. Empirical approaches to bioethics
      are epistemically valuable, i.e., such methods may be necessary in providing and
      verifying basic knowledge about cultural values and norms. Our assumptions in
      moral reasoning can be verified or corrected using these methods. Moral arguments
      can be initiated or adjudicated by data drawn from empirical investigation. One
      may argue that individualistic informed consent, for example, is not compatible
      with the Asian communitarian orientation. But this normative claim uses an
      empirical assumption that may be contrary to the fact that some Asians do value
      and argue for informed consent. Is it necessary and factual to neatly
      characterize some cultures as individualistic and some as communitarian?
      Empirical investigation can provide a reasonable way to inform such
      generalizations. In a multi-cultural context, such as in the Philippines, there
      is a need to investigate the nature of the local ethos before making any appeal
      to authenticity. Otherwise we may succumb to the same ethical imperialism we are
      trying hard to resist. Normative claims that involve empirical premises cannot be
      reasonable verified or evaluated without utilizing empirical methods along with
      philosophical reflection. The integration of empirical methods to the standard
      normative approach to moral reasoning should be reasonably guided by the
      epistemic demands of claims arising from cross-cultural discourse in bioethics.

PMID- 12061378
TI  - The moral foundation of the clinical duties of care: needs, duties and human
      rights.
AB  - It has become fashionable to question attempts to derive internationally agreed
      duties of clinical care from more general theories of human rights. For example,
      some argue that such attempts risk moral abstraction through their neglect for
      the importance of culture and community in shaping moral consciousness and thus
      often unhelpful in the resolution of concrete moral dilemmas within medicine.
      Others denounce the importance of general moral principles altogether in
      bioethics and attempt to articulate what are claimed to be more practical
      approaches to resolving moral conflict. This paper challenges such arguments. It
      does so through arguing that: i) all humans everywhere have the same basic human
      needs; ii) the satisfaction of these needs varies with culture; iii) the
      imputation of moral duties on others entails respect for their right to basic
      need satisfaction, including the right to choose between presumptions about the
      duties and rights of patients which follow from these more general principles and
      v) problems of moral indeterminancy that arise from putting these principles into
      practice can be resolved through associated procedural policies of rational
      negotiation and compromise. The moral importance and practicality of respect for
      individual human rights within the practice of medicine is thus defended. Indeed,
      the paper concludes by arguing that without belief in human rights linked to a
      theory of basic human needs, communitarian theories of morality are incoherent.

PMID- 12061380
TI  - Treatment of poikiloderma of Civatte with the pulsed dye laser: a series of seven
      cases.

PMID- 12061379
TI  - Individual and collective considerations in public health: influenza vaccination
      in nursing homes.
AB  - Many nursing homes have an influenza vaccination policy in which it is assumed
      that express (proxy) consent is not necessary. Tacit consent procedures are more
      efficient if one aims at high vaccination rates. In this paper I focus on
      incompetent residents and proxy consent. Tacit proxy consent for vaccination
      implies a deviance of standard proxy consent requirements. I analyse several
      arguments that may possibly support such a deviance. The primary reason to offer
      influenza vaccination is that vaccinated persons have a significantly reduced
      risk of getting the flu. This reason however cannot support the assumption that
      each nursing home resident is 'better off' if she is vaccinated. Neither can it
      support tacit proxy consent policies. More promising are arguments that take the
      collective nature of infectious diseases into account. A potentially strong, but
      ultimately insufficient, argument for non-express consent is that vaccination
      contributes to prevention of harm to others. Other arguments emphasize the
      importance of group protection: herd immunity. I discuss three collective reasons
      for aiming at herd immunity: solidarity, a common interest in reducing the risk
      of illness, and a common interest in the prevention of an influenza outbreak. The
      latter argument appears to be most important. An outbreak is not just detrimental
      to the health of residents; it is detrimental to their everyday social life as
      well. Outbreaks can be seen as collective evil. My analysis shows that there are
      valid (though not necessarily sufficient) moral arguments for a tacit proxy
      consent policy.

PMID- 12061381
TI  - Utilitarianism and the disabled: distribution of resources.
AB  - Utilitarianism is more convincing than resource egalitarianism or welfare
      egalitarianism as a theory of how resources should be distributed between
      disabled people and nondisabled people. Unlike resource egalitarianism,
      utilitarianism can redistribute resources to the disabled when they would benefit
      more from those resources than nondisabled people. Unlike welfare egalitarianism,
      utilitarianism can halt redistribution when the disabled would no longer benefit
      more than the nondisabled from additional resources. The author considers one
      objection to this view: it has been argued, by Sen and others, that there are
      circumstances under which utilitarianism would unfairly distribute fewer
      resources to the physically disabled than to nondisabled people, on the ground
      that the disabled would derive less benefit from those resources. In response,
      the author claims that critics of utilitarianism have fallaciously exaggerated
      the circumstances under which the disabled would benefit less than the
      nondisabled from additional resources. In those limited circumstances in which
      the disabled really would benefit less from resources, the author argues, it does
      not seem unfair to distribute fewer resources to them.

PMID- 12061382
TI  - Human death--a view from the beginning of life.
AB  - This paper presents a simple argument against definitions of the death of a human
      being in terms of death, or the cessation of functioning, of its brain: a human
      being is alive, and is capable of dying, before it acquires a brain. Although a
      more accurate definition is sketched, it is stressed that it should not be taken
      for granted that it is ethically urgent to work out such a definition. What
      morally matters more than the death of a human being may be something for which
      its death is sufficient, but not necessary, namely the irreversible loss of its
      capacity for consciousness. It is when we lose this capacity that we lose our
      moral standing, as subjects who can be benefited and harmed, and who can have
      rights. But, as is also suggested, the loss of this capacity is ill suited to be
      what the death of a human being definitionally consists of.

PMID- 12061383
TI  - What research with stored samples teaches us about research with human subjects.
AB  - There is widespread discussion concerning the safeguards appropriate for human
      research subjects. Less discussed is the fact that the safeguards one deems
      appropriate depend, in large part, on the model of research participation that
      one assumes. Therefore, to determine what safeguards are appropriate, it is
      necessary first to clarify the competing models of research participation. The
      ostensibly obscure debate over informed consent for research on stored biological
      samples is of particular interest in this regard because such research can
      involve varying subsets of the three central elements of research involvement. As
      a result, analysis of this debate provides an opportunity to identify the
      competing models of research participation. Based on this analysis, this paper
      describes a new model of research participation that is emerging, and considers
      its implications for clinical research.

PMID- 12061384
TI  - Animal genetic manipulation--a utilitarian response.
AB  - I examine the process and outcomes of animal genetic manipulation
      ('transgenesis') with reference to its morally salient features. I consider
      several objections to transgenesis. I examine and reject the alleged intrinsic
      wrongness of 'deliberate genetic sequence alteration,' as I do the notion that
      transgenesis may lead to human genetic manipulation. I examine the alleged
      wrongness of killing inherent in transgenesis, and suggest that the concept of
      'replaceability' successfully justifies such killing, although not for entities
      deemed to possess 'personhood.' I examine 'significant suffering' associated with
      transgenesis and propose the radical conclusion that, although it would be wrong
      to prohibit animal genetic manipulation per se, utilitarians ought to support a
      'default prohibition' on transgenic experiments that entail significant
      suffering.

PMID- 12061385
TI  - Genes and social justice: a Rawlsian reply to Moore.
AB  - In this article I critically examine Adam Moore's claim that the threshold for
      overriding intangible property rights and privacy rights is higher, in relation
      to genetic enhancement techniques and sensitive personal information, than is
      commonly suggested. I argue that Moore fails to see how important advances in
      genetic research are to social justice. Once this point is emphasized one sees
      that the issue of how formidable overriding these rights are is open to much
      debate. There are strong reasons, on grounds of social justice, for thinking the
      importance of such rights is likely to be diminished in the interests of ensuring
      a more just distribution of genes essential to pursuing what John Rawls calls a
      person's 'rational plan of life'.

PMID- 12061386
TI  - Contracting for quality: Medicare's quality improvement organizations.
AB  - This paper examines the role of quality improvement organizations (QIOs, formerly
      known as PROs, or peer review organizations) in improving the quality of medical
      care delivered to Medicare beneficiaries in both fee-for-service and managed care
      environments. It looks at the expansion of the QIOs' portfolio in their new
      contract cycle to include quality improvement activities in nursing homes, home
      health services, and physicians' offices as well as responsibilities for public
      education. The paper explores the evolution of QIOs, changes in their priorities
      over time, and the projects in which they are currently engaged. It also
      considers their role in the formulation and execution of a national quality
      agenda.

PMID- 12061387
TI  - Bad for your health: are gene patents stopping patients getting the latest tests?

PMID- 12061388
TI  - Embryogenesis of the rat heart: the expression of collagenases.
AB  - Little is known about extracellular matrix (ECM) remodeling during heart
      development. Matrix degrading metalloproteinases are possible candidates
      contributing to degradation of ECM during these complex biological events. We
      described here different forms of MMPs, based on their substrate specificity,
      molecular weight, immunolocalization and in situ zymography within embryonic rat
      myocardium at different stages of heart development (from embryonic day - ED12
      until ED21). Murine collagenase-3 (MMP-13), stromelysin (MMP-3) and gelatinases
      A&B (MMP-2 & -9) were expressed in prenatal hearts, as demonstrated by
      quantitative zymography and immunohistochemistry. MMP-2, -3 and -9 were found
      within myocardium of avascular (ED12) and vascularized heart (ED14-21). An
      extensive immunolabeling over the heart trabeculae, epicardial tissue and a
      weaker labeling in the endocardial and truncoconal cushion tissue was observed at
      all stages of the heart development. Utilizing quantitative zymography we found
      that MMP-13 activity gradually increased from ED14-ED16 reaching a plateau from
      ED16-ED21, while MMP-2 activity demonstrated a transient increase starting at
      ED13, peaked at ED16 and declined thereafter. As to MMP-9 activity, it was seen
      only between ED16 and ED 18. In situ zymography with gelatin as a substrate
      represented activity of MMPs within the myocardium of the atria and the
      ventricles and a very strong activity in the interstitial tissue of the
      endocardial and the conotruncal cushion tissue. CONCLUSION: MMPs expressed in
      embryonic heart correspond to all major classes of these enzymes. They may
      contribute to embryonic remodeling of the heart.

PMID- 12061389
TI  - Anti-inflammatory effects of long-lasting locally-delivered human recombinant
      tissue factor pathway inhibitor after balloon angioplasty.
AB  - BACKGROUND: Tissue factor pathway inhibitor (TFPI) has anti-proliferative and
      anti-migratory effects on cultured smooth muscle cells (SMC) in addition to its
      anti-thrombotic activity. Here, we assess how long locally delivered recombinant
      TFPI (rTFPI) remains detectable at the delivery sites and clarify the main
      mechanism by which rTFPI blocks neointimal growth in vivo. METHODS: The iliac
      arteries of 85 Japanese white rabbits were injured using a Cutting Balloon.
      First, to establish the efficacy of local delivery of rTFPI, 5 groups of 3
      rabbits each were examined immediately or 1, 2, 4 or 7 days after delivery. They
      were treated locally with a total amount of 200 microg of rTFPI given at 40
      microg per pulse per minute by means of a Pulse Spray catheter. Thereafter, 34
      rabbits which had received 200 microg of rTFPI after cutting angioplasty were
      compared to the same number of controls regarding thrombosis, inhibition of
      neointimal proliferation and inflammation. RESULTS: A total of 2.6+/-1.6 ng rTFPI
      persisted on the injured vessel 4 days after delivery. rTFPI was still present on
      48 % of the cut sites 7 days after delivery, despite its short half-life in
      plasma. Thrombosis in the rTFPI-treated group was significantly reduced compared
      to the controls. The number of macrophages present within the media and intima
      was significantly decreased at day 7 after delivery of rTFPI. Furthermore, the
      number of Ki-67-positive cells 14 days after rTFPI delivery was significantly
      lower than in controls although there were no significant differences between
      them after 2 days. CONCLUSIONS: Local delivery of rTFPI decreased the degree of
      neointimal formation 4 weeks after TFPI delivery because of anti-inflammatory and
      anti-proliferative effects in addition to, or rather than, via anti-thrombosis.

PMID- 12061390
TI  - Progressive heart failure after myocardial infarction in mice.
AB  - We tested the hypotheses that myocardial infarction in mice would lead to
      progressively worsening heart failure 12-18 weeks later and that exercise testing
      would provide a suitable means to evaluate left ventricular function
      sequentially. C57BL/6 mice (n = 69) underwent left coronary artery ligation (n =
      50) or thoracotomy without ligation (n = 19). Sixteen animals (32%) died within
      24 h of coronary ligation. Twenty additional animals (40%) died between days 3
      and 14, and these mice showed infarct sizes of > 50% of the left ventricle.
      Fourteen animals (28%) that survived two weeks underwent echocardiography and
      treadmill testing 12 and 18 weeks after infarction, with no further mortality.
      Mice were then killed, morphometric assessment made, infarct size evaluated, and
      myocardial norepinephrine content and expression of BNP and ANF measured. Mice
      with infarcts >30% of the left ventricle (n = 6; 12% of original cohort) had left
      ventricular dilation (p < 0.0001) and hypertrophy (p < 0.001), impaired left
      ventricular systolic function (p < 0.0001) and reduced exercise duration (p =
      0.03) and total work (p = 0.03) 12-18 weeks after infarction. Mice with infarcts
      <30% of the left ventricle (n = 8; 16% of original cohort) had no significant
      functional changes or left ventricular remodeling. Hearts from mice with infarcts
      > 30 % had reduced myocardial norepinephrine levels (MI <30%: 177+/-54 pg/mg, n =
      6; MI >30%: 66+/-14 pg/mg wet weight, n = 4; p = 0.005) and increased mRNA
      content of BNP (p < 0.03) and ANF (p = 0.023). Coronary artery occlusion in mice
      provides a relevant model of clinical heart failure that is progressive and can
      be assessed by sequential exercise testing, providing a means to study the
      development of heart failure and its treatment.

PMID- 12061391
TI  - Concomitant expression of heparin-binding epidermal growth factor-like growth
      factor mRNA and basic fibroblast growth factor mRNA in myocardial infarction in
      rats.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is mitogenic
      and chemotactic for many cell types. HB-EGF is induced in pathological states
      which require cell mitogenesis and proliferation, including angiogenesis, and has
      been reported to interact functionally with basic fibroblast growth factor
      (bFGF). To test our hypothesis that HB-EGF mRNA expression is increased in
      myocardial infarction, we used Northern hybridization in rats to investigate the
      expression of HB-EGF and EGF receptor mRNAs expression in the infarct zone
      compared to the expression of bFGF and FGF receptor mRNAs. We also performed in
      situ hybridization to identify the cells responsible for HB-EGF mRNA production.
      HB-EGF mRNA rapidly increased after ligation (mean +/- SE, 5.6+/-0.23-fold
      increase at 6 hours compared to the preligation heart levels) and reached a
      maximum level (9.1+/-0.42-fold increase) around 12 hours. HB-EGF mRNA then
      gradually decreased on day 1 (5.8+/-1.0-fold increase), day 2 (3.2+/-0.94-fold
      increase) and day 3 (1.9+/-0.33-fold increase) after ligation. Parallel changes
      in bFGF mRNA expression were observed (6, 12 hours, days 1, 2 and 3; 3.6+/-0.42-,
      5.3+/-0.12-, 2.3+/-0.12-, 1.7+/-0.03- and 0.95+/-0.03-fold increase,
      respectively). EGF receptor (ErbB-1) mRNA was gradually increased on day 2 (2.4+/
      0.53-fold increase), day 7(4.0+/-0.61-fold increase) and day 14 (7.0+/-0.61-fold
      increase). Similarly, FGF receptor (FGF receptor-1) mRNA was gradually increased
      (days 2,7 and 14; 1.3+/-0.13-, 1.5+/-0.17- and 2.3+/-0.15-fold increase,
      respectively). Reperfusion after a 2-hour ligation (too late to salvage myocytes)
      enhanced HB-EGF (12 hours, 16.8+/-1.8-fold increase) and bFGF (12 hours, 10.4+/
      1.1-fold increase) mRNA expression. The cells responsible for the increased
      production of HB-EGF mRNA were shown by in situ hybridization to be surviving
      myocytes located in the infarct peripheral zone around infarct necrotizing
      tissue. In conclusion, our results demonstrated a rapid increase in HB-EGF mRNA
      expression concomitant with an increase in bFGF mRNA expression, suggesting that
      HB-EGF and bFGF might play some role in the course of pathological changes in the
      infarct in the early inflammatory phase. Reperfusion at times too late to salvage
      myocytes accelerated sequential changes in the expression of both HB-EGF and bFGF
      mRNAs.

PMID- 12061392
TI  - Regulation of the isozymes of protein kinase C in the surviving rat myocardium
      after myocardial infarction: distinct modulation for PKC-alpha and for PKC-delta.
AB  - OBJECTIVE: The goal of this study was to clarify the regulation of the isozymes
      of protein kinase C (PKC) in the process of remodeling after myocardial
      infarction. METHODS: An in vivo model of regional myocardial infarction induced
      by ligation of the left anterior coronary artery in rats was used. Hemodynamic
      parameters and the heart and lung weights were determined 1 week and 1, 2 and 3
      months after operation. In transmural biopsies from the non-ischemic left
      ventricular wall of the infarcted heart, PKC activity (ELISA) and the expression
      of its major isozymes, PKC-alpha, PKC-delta and PKC-epsilon (Westernblot
      analysis) were determined. RESULTS: As early as one week after myocardial
      infarction, heart weight and left ventricular enddiastolic pressures were
      significantly increased. Lung weights increased after 2 - 3 months, indicating
      progressive pulmonary congestion. The activity of PKC was significantly increased
      about 1.8-fold after 1 week, decreasing progressively in the later time course.
      Whereas the expression of PKC-epsilon did not change, PKC-alpha was increased
      after 1 month (157%) and then returned to baseline values. In contrast, PKC-delta
      expression was significantly augmented after 2 and 3 months of myocardial
      infarction (187%). CONCLUSIONS: These data demonstrate for the first time that in
      the remodeling heart after myocardial infarction, a subtype-selective regulation
      of the PKC isozymes occurs: The upregulation of PKC-alpha coincides with the
      development of hypertrophy, whereas the extensive upregulation of PKC-delta
      outlasts the process of developing hypertrophy and persists in the failing heart.
      The trigger mechanisms for this newly characterized process remains to be
      elucidated.

PMID- 12061393
TI  - A1 adenosine receptor overexpression decreases stunning from anoxia
      reoxygenation: role of the mitochondrial K(ATP) channel.
AB  - Myocardial A1 adenosine receptor (A1AR) overexpression protects hearts from
      ischemia-reperfusion injury; however, the effects during anoxia are unknown. We
      evaluated responses to anoxia-reoxygenation in wild-type (WT) and transgenic
      (Trans) hearts with approximately 200-fold overexpression of A1ARs. Langendorff
      perfused hearts underwent 20 min anoxia followed by 30 min reoxygenation. In WT
      hearts peak diastolic contracture during anoxia was 45+/-3 mmHg, diastolic
      pressure remained elevated at 18+/-3 mmHg after reoxygenation, and developed
      pressure recovered to 52+/-4% of pre-anoxia. A1AR overexpression reduced hypoxic
      contracture to 29+/-4 mmHg, and improved recovery of diastolic pressure to 8+/-1
      mmHg and developed pressure to 76+/-3% of pre-anoxia. Mitochondrial K(ATP)
      blockade with 100 microM 5-hydroxydecanoate (5-HD) increased hypoxic contracture
      to 73+/-6 mmHg in WT hearts, reduced post-hypoxic recoveries of both diastolic
      (40+/-5 mmHg) and developed pressures (33+/-3 %). In contrast, 5-HD had no effect
      on hypoxic contracture (24+/-8 mmHg), or post-hypoxic diastolic (10+/-2 mmHg) and
      developed pressures (74+/-3%) in Trans hearts. In summary, (i) A1AR
      overexpression improves myocardial tolerance to anoxia-reoxygenation, (ii)
      intrinsic mitochondrial K(ATP) channel activation decreases hypoxic contracture
      and improves functional recovery in wild-type hearts, and (iii) mitochondrial
      K(ATP) channels do not appear to play a major role in the functional protection
      from anoxia afforded by A1AR overexpression.

PMID- 12061394
TI  - Early intervention with a potent endothelin-A/endothelin-B receptor antagonist
      aggravates left ventricular remodeling after myocardial infarction in rats.
AB  - Intervention with selective endothelin (ET)A receptor antagonists within 24h
      after myocardial infarction (MI) in rats has been reported to aggravate left
      ventricular (LV) remodeling. In contrast, beneficial effects are reported when
      initiation of treatment is delayed 7 days or more after MI. However, bosentan, a
      mixed ET(A)/ET(B) receptor antagonist with low affinity for the ET receptors, has
      been shown to exert beneficial effects independent of the time point of
      initiation of treatment after MI. The aim of the present study was to investigate
      to what extent early intervention with a mixed ET(A)/ET(B) receptor antagonist
      with higher affinity at the ET receptors (SB 209670) would also exert beneficial
      effects on postinfarction LV remodeling. After ligation of the left coronary
      artery, rats were randomized to treatment with SB 209670 (6.25 mg x kg(-1) SC
      b.i.d., n = 10) or vehicle (n = 12) for 26 days, starting 48h after MI. Treatment
      with SB 209670 adversely affected the postinfarction remodeling process causing
      further dilatation of the LV (LV end-diastolic diameter: 10.4+/-0.5 vs 9.1+/-0.2
      mm; LV end-systolic diameter: 8.5+/-0.4 vs 7.2+/-0.2 mm, P < 0.05). However, SB
      209670 did not significantly affect infarct size, compensatory cardiac
      hypertrophy, nor the myocardial mRNA levels of procollagen type I and III, and
      prolyl 4-hydroxylase and lysyl oxidase, 2 important enzymes affecting collagen
      secretion, stability and functionality. In addition, SB 209670 had no significant
      effects on LV collagen cross-linking or extent of fibrosis. Thus, our data
      demonstrate that early intervention with a potent, mixed ET(A)/ET(B) receptor
      antagonist after MI may promote dilatation of the LV without significant
      alterations of infarct size and extracellular matrix composition. Our data
      support the notion that the timing of initiation of ET receptor antagonism after
      MI is critical and that potent ET receptor antagonists may be harmful during the
      first few days after MI.

PMID- 12061395
TI  - Coronary blood flow control is impaired at rest and during exercise in conscious
      diabetic dogs.
AB  - This study tested whether diabetes mellitus impairs coronary blood flow control
      sufficiently to alter the balance between myocardial oxygen delivery and
      metabolism. Dogs (n = 7) were instrumented with catheters in the aorta and
      coronary sinus, and with a flow transducer on the circumflex coronary artery.
      Coronary blood flow, myocardial oxygen consumption (MVO2), heart rate and aortic
      pressure were measured at rest and during treadmill exercise before and after
      induction of diabetes with alloxan monohydrate (40 - 60 mg/kg). Arterial plasma
      glucose concentration increased from 4.6+/-0.2 mM in non-diabetic, control dogs
      to 20.2+/-2.3 mM one week after alloxan injection. In non-diabetic control dogs,
      exercise increased MVO2 3.1-fold, coronary blood flow 2.7-fold, and heart rate
      2.4-fold. Coronary venous PO2 decreased from 19.4+/-0.6 mmHg at rest to 14.7+/
      0.7 mmHg during exercise. Diabetes significantly attenuated exercise coronary
      hyperemia and reduced coronary venous PO2 at rest (15.6+/-0.5 mmHg) and during
      exercise (12.6+/-0.8 mmHg). Diabetes also significantly reduced myocardial oxygen
      delivery at each level of exercise. Acute hyperglycemia alone did not alter
      exercise-induced coronary vasodilation or reduce coronary venous PO2. These
      findings demonstrate that experimental diabetes attenuates functional coronary
      hyperemia and impairs the balance between coronary blood flow and myocardial
      metabolism. However, this deleterious effect is not related to acute
      hyperglycemia but to the chronic disease process of diabetes mellitus.

PMID- 12061396
TI  - The expression of heat shock protein 60 in myocardium of patients with chronic
      atrial fibrillation.
AB  - OBJECTIVE: Cardiomyocytes respond to stress with the expression of different heat
      shock proteins (HSP). HSP60 is induced by various stress factors. The aim of this
      study was to investigate the expression of HSP60 in human atrial fibrillation
      (AF). METHOD: Right atrial samples from 14 patients undergoing elective cardiac
      surgery were excised and immediately frozen in liquid nitrogen. Eight patients
      had chronic AF and six patients were in sinus rhythm. The HSP60 protein level was
      determined by SDS-PAGE, Western blot and quantified by optical densitometry
      according to the immunoreactive bands of actin. RESULTS: In myocardial samples
      from patients with chronic AF, we found a more than 2.5-fold increase in HSP60
      expression compared to atrial myocardium of patients in sinus rhythm. CONCLUSION:
      This result indicates an up regulation of HSP60 in response to chronic atrial
      fibrillation.

PMID- 12061397
TI  - A review on usnic acid, an interesting natural compound.
AB  - Lichens are a world-widespread consortium of fungal and photosynthetic partners.
      Usnic acid is one of the most common and abundant lichen metabolites, well known
      as an antibiotic, but also endowed with several other interesting properties.
      This review summarises the most relevant studies on usnic acid, focusing on a
      number of biological activities in different fields. On the basis of the existing
      literature, usnic acid seems to be an exclusive lichen product. No synthetic
      derivatives more effective than the natural form are known. Both the (+) and (-)
      enantiomers of usnic acid are effective against a large variety of Gram-positive
      (G+) bacterial strains, including strains from clinical isolates, irrespective of
      their resistant phenotype. Of particular relevance is the inhibition of growth of
      multi-resistant strains of Streptococcus aureus, enterococci and mycobacteria.
      The (+)-usnic acid enantiomer appears to be selective against Streptococcus
      mutans without inducing perturbing side effects on the oral saprophyte flora. On
      the other hand, the (-)-usnic acid enantiomer is a selective natural herbicide
      because of its blocking action against a specific key plant enzyme. Other
      recognised characteristics of usnic acid are ultraviolet absorption and
      preserving properties. The toxicology, the in vitro anti-inflammatory effects and
      the mechanism of action of usnic acid need to be investigated in greater detail
      in order to reach clinical trials and to allow further applications. Furthermore,
      more research is needed to make possible intensive lichen culture, in order to
      produce large quantities of lichen substances for pharmaceutical, cosmetic and
      agricultural purposes. Some biological aspects, i.e. the possible biological
      roles of usnic acid, are discussed.

PMID- 12061398
TI  - Ecology and ecophysiology of tree stems: corticular and wood photosynthesis.
AB  - Below the outer peridermal or rhytidomal layers, most stems of woody plants
      possess greenish tissues. These chlorophyll-containing tissues (the
      chlorenchymes) within the stems are able to use the stem internal CO2 and the
      light penetrating the rhytidome to photoassimilate and produce sugars and starch.
      Although net photosynthetic uptake of CO2 is rarely found, stem internal re
      fixation of CO2 in young twigs and branches may compensate for 60-90% of the
      potential respiratory carbon loss. Isolated chlorenchymal tissues reveal rather
      high rates of net photosynthesis (being up to 75% of the respective rates for
      leaf photosynthesis). Corticular photosynthesis is thus thought to be an
      effective mechanism for recapturing respiratory carbon dioxide before it diffuses
      out of the stem. Furthermore, chloroplasts of the proper wood or pith fraction
      also take part in stem internal photosynthesis. Although there has been no strong
      experimental evidence until now, we suggest that the oxygen evolved during wood
      or pith photosynthesis may play a decisive role in avoiding/reducing stem
      internal anaerobiosis.

PMID- 12061399
TI  - A novel function for the pineal organ in the control of swim depth in the
      Atlantic halibut larva.
AB  - The pineal organ of vertebrates is a photo-sensitive structure that conveys
      photoperiod information to the brain. This information influences circadian
      rhythm and related metabolic processes such as thermoregulation, hatching time,
      body growth, and the timing of reproduction. This study demonstrates extra-ocular
      light responses that control swim depth in the larva of the Atlantic halibut,
      Hyppoglosus hyppoglosus. Young larvae without a functional eye (<29 days) swim
      upwards after an average delay of 5 s following the onset of a downwelling light
      stimulus, but sink downwards a few seconds later. Older larvae (> or = 29 days),
      which possess a functional eye, swim immediately downwards (microsecond delay)
      following the onset of the light stimulus, but proceed to swim upwards several
      seconds later. These two response patterns are thus opposite in polarity and have
      different time kinetics. Because the pineal organ of the Atlantic halibut
      develops during the embryonic stage, and because it is the only centre in the
      brain that expresses functional visual pigments (opsins) at early larval stages,
      it is the only photosensory organ capable of generating the extra-ocular
      responses observed.

PMID- 12061400
TI  - Feminization of genetic males by a symbiotic bacterium in a butterfly, Eurema
      hecabe (Lepidoptera: Pieridae).
AB  - Wolbachia are symbiotic bacteria found in many arthropods and filarian nematodes.
      They often manipulate the reproduction of host arthropods. In the present study,
      female-biased sex-ratio distortion in the butterfly Eurema hecabe was
      investigated. Breeding experiments showed that this distorted sex ratio is
      maternally inherited. When treated with tetracycline, adult females of the
      thelygenic line produced male progeny only. After PCR using Wolbachia-specific
      primers for the ftsZ gene a positive result was seen in the thelygenic females,
      but not in male progeny from tetracycline-treated females, or individuals from a
      Tokyo population with normal sex ratio and reproduction. Cytological observations
      showed that thelygenic females lack the sex chromatin body (W chromosome). The
      results strongly suggest that the sex-ratio distortion in E. hecabe is due to
      feminization of genetic males by Wolbachia.

PMID- 12061401
TI  - The flavo-enzyme xanthine oxidase is under circadian control in the marine alga
      Gonyaulax.
AB  - The activity of xanthine oxidoreductases (xanthine oxidase, XO, EC 1.2.3.2 and
      xanthine dehydrogenase, XDH, EC 1.1.1.204) in partially purified extracts of
      Gonyaulax polyedra was measured over 24 h both in a light:dark cycle and in
      constant light. This is the first demonstration of xanthine oxidoreductase in a
      unicellular alga. The activity of the O2-dependent form (XO) was found to be 15
      times higher in light than in darkness. The same time-of-day specific differences
      persisted in constant light, demonstrating a control of XO by the circadian
      clock. In contrast, the activity of the NAD-dependent form (XDH) is not under
      circadian control. Because pharmacological inhibition of XO also blocks the
      effect of blue light on the Gonyaulax circadian clock, the possible relationship
      between XO and light reception in this unicellular alga will be discussed.

PMID- 12061402
TI  - Docile sitters and active fighters in paper wasps: a tale of two queens.
AB  - Ropalidia marginata and Ropalidia cyathiformis are sympatric, primitively
      eusocial paper wasps widely distributed in peninsular India. We compare the two
      species, especially their queens, in an attempt to begin to understand the role
      of the power of queens over their workers, in social organisation and evolution.
      Queens of R. marginata have lower levels of activity, rates of interactions and
      dominance behaviour, compared with queens of R. cyathiformis. For the same
      variables, R. marginata queens are either indistinguishable from or have lower
      values than their workers, while R. cyathiformis queens have higher values than
      their workers. R. marginata queens never occupy the top rank while R.
      cyathiformis queens are always at the top of the behavioural dominance
      hierarchies of their colonies. R. marginata queens thus do not appear to use
      dominance behaviour to suppress reproduction by their workers, while R.
      cyathiformis queens appear to do so. These different mechanisms used by the two
      queens to regulate worker reproduction give them different powers over their
      workers, because R. marginata queens are completely successful in suppressing
      reproduction by their nestmates while in R. cyathiformis colonies, other
      individuals also sometimes lay eggs. There is also some evidence that the
      different powers of the queens result in different mechanisms of regulation of
      worker foraging in the two species--decentralised, self-regulation in R.
      marginata and relatively more centralised regulation by the queen in R.
      cyathiformis. Thus we show here, perhaps for the first time, that the power of
      the queens over their workers can have important consequences for social
      organisation and evolution.

PMID- 12061403
TI  - A new giant pterosaur with a robust skull from the latest cretaceous of Romania.
AB  - A new giant pterosaur, Hatzegopteryx thambema, nov.gen., nov.sp., from the
      Maastrichtian Densus-Ciula Formation of Romania is remarkable for its very large
      size (estimated wing span > or = 12 m) and for the robustness of its large skull,
      which may have been nearly 3 m long. The stout skull bones contrast with the
      usually thin and slender skull elements of other pterosaurs, and raise the
      question of how the weight of the skull was reduced in order to make flight
      possible. The answer probably lies in the very peculiar internal structure of the
      bones, which consists of a dense network of very thin trabeculae enclosing small
      alveoli. This structure is reminiscent of expanded polystyrene and, like it,
      probably combined strength with lightness.

PMID- 12061404
TI  - Transferability of HIV by arthropods supports the hypothesis about transmission
      of the virus from apes to man.
AB  - The primate Pan troglodytes troglodytes, a chimpanzee subspecies, has recently
      been defined as a natural animal host of the human immunodeficiency virus (HIV).
      Apes are traditionally hunted in Africa and are offered for sale in open-air meat
      markets. The bloody carcasses are regularly covered with blood-feeding flies,
      amongst them possibly the stable fly (Stomoxvs calcitrans L.). a cosmopolitically
      occurring biting fly. This fly is the effective vector for the retrovirus causing
      equine infectious anemia [corrected]. According to laboratory experiments, the
      infectivity of ingested HIV is not reduced in the regurgitates of this fly. These
      findings are combined to explain the mechanism for a possible primary
      transmission of HIV from ape to man.

PMID- 12061405
TI  - Individual differences in rates of change in cognitive abilities of older
      persons.
AB  - The authors examined change in cognitive abilities in older Catholic clergy
      members. For up to 6 years, participants underwent annual clinical evaluations,
      which included a battery of tests from which summary measures of 7 abilities were
      derived. On average, decline occurred in each ability and was more rapid in older
      persons than in younger persons. However, wide individual differences were
      evident at all ages. Rate of change in a given domain was not strongly related to
      baseline level of function in that domain but was moderately associated with
      rates of change in other cognitive domains. The results suggest that change in
      cognitive function in old age primarily reflects person-specific factors rather
      than an inevitable developmental process.

PMID- 12061406
TI  - Change in cognitive functioning associated with apoE genotype in a community
      sample of older adults.
AB  - The influence of a genetic risk factor, apolipoprotein E (apoE) epsilon4 variant,
      was assessed in older adults aged 70 to 94 on 3 occasions over 7 years. The
      results of latent growth curve analyses are reported for individuals genotyped
      for apoE at the 2nd measurement occasion (n = 601) and for a subsample of
      individuals without probable or definite dementia during the 1st or 2nd occasion
      (n = 434). ApoE-epsilon4 status was a significant predictor of level and change
      in memory performance and change in speed performance in the full sample, and of
      initial level and change in memory performance in the nondemented subsample.
      These results support previous findings that apoE-epsilon4 is associated with
      accelerated memory deterioration in individuals without clinical dementia.

PMID- 12061407
TI  - Aging and monitoring associative learning: is monitoring accuracy spared or
      impaired?
AB  - Mixed lists of associatively related and unrelated paired associates were used to
      study monitoring of associative learning. Older and younger adults produced above
      chance levels of relative accuracy, as measured by intraindividual correlations
      (gamma) of judgments of learning (JOLs) with item recall. JOLs were strongly
      influenced by relatedness, and this effect was greater for older adults. Relative
      accuracy was higher for unrelated than for related pairs. Correlations of JOLs
      with item recall for a randomly yoked learner indicated that access to one's own
      encoding experiences increased relative accuracy. Both age groups manifested a
      contrast effect (lower JOLs for unrelated items when mixed with related items).
      Aging appears to spare monitoring of encoding, even though it adversely affects
      associative learning.

PMID- 12061409
TI  - College-educated women's personality development in adulthood: perceptions and
      age differences.
AB  - Adulthood encompasses a large time span and includes a series of psychosocial
      challenges (E. H. Erikson, 1950). Five aspects of personality (identity
      certainty, confident power, concern with aging, generativity, and personal
      distress) were assessed in a cross-sectional study of college-educated women who
      at the time of data collection were young adults (age: M = 26 years), middle-aged
      adults (age: M = 46 years), or older adults (age: M = 66 years). Respondents
      rated each personality domain for how true it was of them at the time, and they
      then rated the other 2 ages either retrospectively or prospectively. Results are
      discussed with attention to the ways in which women's adult development may have
      been shaped by experiences particular to both gender and birth cohort, and to how
      these women fit with E. H. Erikson's theory of adult development.

PMID- 12061408
TI  - Does priming specific syllables during tip-of-the-tongue states facilitate word
      retrieval in older adults?
AB  - This experiment investigated whether phonological priming of syllables helps
      resolve tip-of-the-tongue (TOT) states in young and older adults. Young, young
      old, and old-old adults read general knowledge questions and responded "know,"
      "TOT," or "don't know" accordingly. Participants then read a list of 10 words
      that included 3 phonological primes corresponding solely to the first, middle, or
      last syllable of the target word. Young and young-old adults resolved more TOTs
      after first-syllable primes, but old-old adults showed no increase in TOT
      resolution following any primes. These results indicate that presentation of the
      first syllable of a missing word strengthens the weakened phonological
      connections that cause TOTs and increases word retrieval, but not for old-old
      adults who experience greater deficits in the transmission of priming across
      these connections.

PMID- 12061410
TI  - Computational explorations of the influence of structured knowledge on age
      related cognitive decline.
AB  - Experience in a domain can sometimes offset cognitive declines that occur with
      aging. Using a series of neural network simulations of learning chess opening
      positions, the authors investigated how structured knowledge in a distributed
      representation may influence age-related declines. Aging manipulations
      implemented as modulations of neural noise showed increased knowledge as being
      protective of performance on a chess memory span task, whereas changes in neural
      plasticity and neural loss lead to main effects without interactions and steeper
      declines for the initially more able. The models could also simulate the increase
      in variability in older groups.

PMID- 12061411
TI  - Welfare participation and social support in late life.
AB  - The purpose of this study was to examine the relationships among participation in
      welfare programs, gender, and change in social support in adults aged 65 and
      older. It was hypothesized that older men receiving public assistance would
      encounter more social network problems than older women on welfare. The findings
      reveal that during the 7-year study older men in receipt of welfare benefits,
      compared with older women on welfare, received less social support from others,
      were more dissatisfied with the assistance they got, and encountered more
      negative interaction from informal social network members (i.e., family and
      friends). The results suggest that those who administer welfare programs, as well
      as public policymakers, should consider developing interventions that address the
      wider psychosocial problems associated with receiving public assistance.

PMID- 12061412
TI  - Individual variation for cognitive decline: quantitative methods for describing
      patterns of change.
AB  - What are the best quantitative methods for studying cognitive decline? This
      question was investigated in a sample of 638 individuals aged 50 years and older
      from the Swedish Adoption/Twin Study of Aging. A battery of cognitive tests
      tapping multiple domains was administered to each individual from 2 to 7 times
      over a span of 10 years. Four methods of operationalizing cognitive decline were
      compared: change scores, a criterion-based method, least squares, and random
      effects regression (RER). The RER results were most consistent with a significant
      decline across measures and differences between demented and nondemented
      individuals. Predicted slopes from the RER model also showed the strongest
      interrelationships within and across cognitive domains as indicated by factor
      analysis results and stronger associations with demographic, health, and
      psychosocial predictors.

PMID- 12061413
TI  - Efficacy of two behavioral treatment programs for comorbid geriatric insomnia.
AB  - Older adults with comorbid insomnia and medical illness have been excluded from
      behavioral treatment research, but recent evidence suggested that such treatments
      would be effective with this population. In this study, 38 older adults with
      comorbid insomnia were randomized to 1 of 3 conditions: classroom cognitive
      behavioral treatment (CBT), home-based audio relaxation treatment (HART), or
      delayed-treatment control. Compared to the control group, the CBT group had
      significant changes in 5 of 7 self-report measures of sleep at the 4-month follow
      up. The HART group obtained significant outcomes on 3 of 7 measures. Wrist
      actigraphy measures and secondary-outcome measures did not yield significant
      findings for either treatment. Clinically significant changes at follow-up were
      obtained for 54% of patients in CBT, 35% in HART, and 6% in the control group
      when treatment dropouts were included. Although not as effective as in-person
      CBT, home interventions may have utility as a first-line, low-cost treatment.

PMID- 12061414
TI  - Models of visuospatial and verbal memory across the adult life span.
AB  - The authors investigated the distinctiveness and interrelationships among
      visuospatial and verbal memory processes in short-term, working, and long-term
      memories in 345 adults. Beginning in the 20s, a continuous, regular decline
      occurs for processing-intensive tasks (e.g., speed of processing, working memory,
      and long-term memory), whereas verbal knowledge increases across the life span.
      There is little differentiation in the cognitive architecture of memory across
      the life span. Visuospatial and verbal working memory are distinct but highly
      interrelated systems with domain-specific short-term memory subsystems. In
      contrast to recent neuroimaging data, there is little evidence for
      dedifferentiation of function at the behavioral level in old compared with young
      adults. The authors conclude that efforts to connect behavioral and brain data
      yield a more complete understanding of the aging mind.

PMID- 12061415
TI  - Aging and visual marking: selective deficits for moving stimuli.
AB  - The selective processing of new visual information can be facilitated by the top
      down inhibition of old stimuli already in the visual field, a capacity-limited
      process termed visual marking (D. G. Watson & G. W. Humphreys, 1997). Three
      experiments assessed the effects of aging on visual marking using stationary
      (Experiment 1) and moving (Experiments 2 and 3) items. For young participants,
      visual marking was observed in all experiments. For older participants, visual
      marking was observed only with stationary items. The results are not consistent
      with any simple account of general age-related decrements and provide further
      support for the deployment of different methods of visual marking depending on
      the properties of the old items and the current task demands.

PMID- 12061416
TI  - Perceived control of life regrets: good for young and bad for old adults.
AB  - Age differences in the associations among intensity of regret, control
      attributions, and intrusive thoughts were investigated (N = 122, age range = 20
      87 years). Given that the opportunities to overcome regrettable behavior decline
      with age, older adults' attributions of low internal control were expected to
      serve self-protective functions and facilitate deactivation of regret. In younger
      adults, by contrast, high levels of internal-control attributions might
      facilitate active change of regrettable behavior, resulting in low intensities of
      regret. The results showed that internal-control attributions were related to
      high intensity of regret and intrusive thoughts in older adults. Among younger
      adults, however, internal-control attributions were associated with low intensity
      of regret and low levels of intrusive thoughts.

PMID- 12061417
TI  - Implicit learning of higher order sequences in middle age.
AB  - Previous studies have demonstrated age-related deficits in implicit learning of
      higher order sequences in comparisons of college-age and elderly adults (e.g., J.
      H. Howard & D. V. Howard, 1997). This study examined whether these age deficits
      begin in middle age. Results showed a reliable age-related deficit in pattern
      sensitivity in "older" compared with "younger" middle-aged people, and age
      reliably predicted sensitivity to the sequence by using both speed and accuracy
      measures. The results are consistent with an age-related decline in a generic
      cognitive resource as reflected in T. A. Salthouse's (1996) simultaneity
      mechanism of cognitive aging.

PMID- 12061418
TI  - Burst synchrony patterns in hippocampal pyramidal cell model networks.
AB  - Types of. mechanisms for and stability of synchrony are discussed in the context
      of two-compartment CA3 pyramidal cell and interneuron model networks. We show how
      the strength and timing of inhibitory and excitatory synaptic inputs work
      together to produce either perfectly synchronized or nearly synchronized
      oscillations, across different burst or spiking modes of firing. The analysis
      shows how excitatory inputs tend to desynchronize cells, and how common, slowly
      decaying inhibition can be used to synchronize them. We also introduce the
      concept of 'equivalent networks' in which networks with different architectures
      and synaptic connections display identical firing patterns.

PMID- 12061419
TI  - A Bayesian attractor network with incremental learning.
AB  - A realtime online learning system with capacity limits needs to gradually forget
      old information in order to avoid catastrophic forgetting. This can be achieved
      by allowing new information to overwrite old, as in a so-called palimpsest
      memory. This paper describes an incremental learning rule based on the Bayesian
      confidence propagation neural network that has palimpsest properties when
      employed in an attractor neural network. The network does not suffer from
      catastrophic forgetting, has a capacity dependent on the learning time constant
      and exhibits faster convergence for newer patterns.

PMID- 12061420
TI  - Complex dynamics and the structure of small neural networks.
AB  - The discrete-time dynamics of small neural networks is studied empirically, with
      emphasis laid on non-trivial bifurcation scenarios. For particular two- and three
      neuron networks interesting dynamical properties like periodic, quasi-periodic
      and chaotic attractors are observed, many of them co-existing for one and the
      same set of parameters. An appropriate equivalence class of networks is defined,
      describing them as parametrized dynamical systems with identical dynamical
      capacities. Combined symmetries in phase space and parameter space are shown to
      generate different representatives of such a class. Moreover, conditions on the
      connectivity structure are suggested, which guarantee the existence of complex
      dynamics for a considered equivalence class of network configurations.

PMID- 12061421
TI  - Self-organizing continuous attractor networks and path integration: one
      dimensional models of head direction cells.
AB  - Some neurons encode information about the orientation or position of an animal,
      and can maintain their response properties in the absence of visual input.
      Examples include head direction cells in rats and primates, place cells in rats
      and spatial view cells in primates. 'Continuous attractor' neural networks model
      these continuous physical spaces by using recurrent collateral connections
      between the neurons which reflect the distance between the neurons in the state
      space (e.g. head direction space) of the animal. These networks maintain a
      localized packet of neuronal activity representing the current state of the
      animal. We show how the synaptic connections in a one-dimensional continuous
      attractor network (of for example head direction cells) could be self-organized
      by associative learning. We also show how the activity packet could be moved from
      one location to another by idiothetic (self-motion) inputs, for example
      vestibular or proprioceptive, and how the synaptic connections could self
      organize to implement this. The models described use 'trace' associative synaptic
      learning rules that utilize a form of temporal average of recent cell activity to
      associate the firing of rotation cells with the recent change in the
      representation of the head direction in the continuous attractor. We also show
      how a nonlinear neuronal activation function that could be implemented by NMDA
      receptors could contribute to the stability of the activity packet that
      represents the current state of the animal.

PMID- 12061422
TI  - Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy
      and pre-eclampsia.
AB  - BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to
      have different pathophysiology. However, 15-25% of pregnant women initially
      diagnosed as having TH develop PE. To clarify the immuno-pathogenetical
      connections between the two syndromes, we studied the pattern of T helper cell
      (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in
      normal pregnancy (NP) and pregnancies complicated with TH and PE. METHODS: Third
      trimester decidual tissue was obtained by curettage of uterine cavity during
      elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients.
      Cell suspensions were prepared by an electromechanical dispersal method and
      centrifugated using a standard gradient sedimentation technique. Isolated
      lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine,
      penicillin, streptomycin) and cultured for 72 h with or without mitogen
      phytohaemaglutinine (PHA). The enzyme-linked immunosorbent assay method was used
      for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon
      gamma (IFN-gamma) in culture supernatant. STATISTICAL ANALYSIS: The Kruskal
      Wallis and the Mann-Whitney U tests were used (p < 0.05). RESULTS: Both
      spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was
      decreased in PE patients compared with TH and NP patients. The concentration of
      Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and
      PE. CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are
      syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and
      TH seems to be an intermediate step to PE.

PMID- 12061423
TI  - T cells expressing the gammadelta receptor are essential for Th2-mediated
      inflammation in patients with acute exacerbation of asthma.
AB  - OBJECTIVE: T lymphocytes have a central regulatory role in the pathogenesis of
      asthma. The objective of this study was to characterize immunologically the
      activation stage of asthma and the functional profile of lymphocytes from induced
      sputum, with particular emphasis on gammadelta T cells. METHODS: Induced sputum
      was collected from 10 patients with acute exacerbation of asthma, and from
      healthy controls. The expression of activation markers on freshly isolated
      induced sputum lymphocytes and T-cell subsets was analyzed by double
      immunofluorescent staining and flow cytometry. Fas ligand (FasL) was determined
      by reverse transcriptase-polymerase chain reaction analysis. The phenotype of
      gammadelta T-cell subpopulations was tested by A13 and BB3 monoclonal antibodies.
      In this context, the functional profile of gammadelta T cells was tested in a
      chromium releasing test. RESULTS: A significantly decreased proportion of
      alphabeta T cells and an increased proportion of gammadelta T cells, CD56+ cells
      and CD8+ gammadelta T cells were found in asthma patients compared with healthy
      controls. In asthmatic patients, there is a significantly increased proportion of
      T cells expressing CD69 and CD25 antigen. After stimulation of gammadelta T
      cells, an increased expression of intracellular tumour necrosis factor-alpha,
      interleukin (IL)-4 and IL10 cytokines were found at higher levels than controls.
      Interferon-gamma was observed at similar levels in asthma patients and healthy
      controls. Freshly isolated T-cell receptor (TCR) gammadelta+ cells exhibited an
      increased percentage of FasL in our patient group. FasL mRNA was detected in TCR
      gammadelta+ cells before and after IL2 stimulation. TCR gammadelta+ cells were
      cytotoxic against the K562 cell line. This natural killer activity was mediated
      by the A13-positive subpopulation. CONCLUSION: The presence of cytokines
      producing gammadelta cells in induced sputum of asthmatic patients is consistent
      with regulatory activities. These cells display also cytotoxic function.

PMID- 12061424
TI  - Increments in cytokines and matrix metalloproteinases in skeletal muscle after
      injection of tissue-damaging toxins from the venom of the snake Bothrops asper.
AB  - Envenomations by the snake Bothrops asper are characterized by prominent local
      tissue damage (i.e. myonecrosis), blistering, hemorrhage and edema. Various
      phospholipases A2 and metalloproteinases that induce local pathological
      alterations have been purified from this venom. Since these toxins induce a
      conspicuous inflammatory response, it has been hypothesized that inflammatory
      mediators may contribute to the local pathological alterations described. This
      study evaluated the local production of cytokines and matrix metalloproteinases
      (MMPs) as a consequence of intramuscular injections of an Asp-49 myotoxic
      phospholipase A2 (myotoxin III (MT-III)) and a P-I type hemorrhagic
      metalloproteinase (BaP1) isolated from B. asper venom. Both enzymes induced
      prominent tissue alterations and conspicuous increments in interleukin (IL)
      1beta, IL-6 and a number of MMPs, especially gelatinase MMP-9, rapidly after
      injection. In contrast, no increments in tumor necrosis factor-alpha (TNF-alpha)
      and interferon-gamma were detected. In agreement, MT-III and BaP1 did not induce
      the synthesis of TNF-alpha by resident peritoneal macrophages in vitro. Despite
      the conspicuous expression of latent forms of MMPs in muscle, evidenced by
      zymography, there were no increments in activated MMP-2 and only a small increase
      in activated MMP-9, as detected by a functional enzymatic assay. This suggests
      that MMP activity was regulated by a highly controlled activation of latent forms
      and, probably, by a concomitant synthesis of MMP inhibitors. Since no hemorrhage
      nor dermonecrosis were observed after injection of MT-III, despite a prominent
      increase in MMP expression, and since inflammatory exudate did not enhance
      hemorrhage induced by BaP1, it is suggested that endogenous MMPs released in the
      tissue are not responsible for the dermonecrosis and hemorrhage characteristic of
      B. asper envenomation. Moreover, pretreatment of mice with the peptidomimetic MMP
      inhibitor batimastat did not reduce myotoxic nor edema-forming activities of MT
      III, suggesting that MMPs do not play a prominent role in the pathogenesis of
      these effects in this experimental model. It is concluded that MT-III and BaP1
      induce a local inflammatory response associated with the synthesis of IL-1beta,
      IL-6 and MMPs. MMPs do not seem to play a prominent role in the acute local
      pathological alterations induced by these toxins in this experimental model.

PMID- 12061425
TI  - Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer
      linked with zinc.
AB  - BACKGROUND: Peptidoglycan monomer (PGM), which was originally prepared by
      biosynthesis from culture fluids of penicillin-treated Brevibacterium
      divaricatum, is an immunostimulator, the activities of which might be improved by
      addition of zinc (Zn) to the basic molecule. METHODS: To test the possible
      cytotoxic effects of this new analogue, we analyzed the ability of PGM-Zn and PGM
      to change the phenotypic profile of hepatic and splenic mononuclear lymphatic
      cells and to affect the growth of malignant T-cell line YAC-1 and syngeneic
      thymocytes. RESULTS: Pretreatment of C57BL/6 mice primarily with PGM-Zn over 6
      days (10/mg/kg intraperitoneally) significantly enhanced the proportions of
      NK1.1high+, CD4-CD8-, CD69+, and CD3intermediate/NK1.1+/IL2R-beta+ (NKT) cells in
      the liver, and major histocompatibility complex class II+, CD69+, and CD8+ cells
      in the spleen. Both types of cells were highly cytotoxic against YAC-1 and
      syngeneic thymocytes, increasing the destruction of YAC-1 by 70% on addition of
      hepatic cells and by 30% on addition of splenic cells. Destruction of thymocytes
      increased by 10 and 50%, respectively. CONCLUSION: The results point to PGM-Zn as
      a potent cytotoxicity-inducing agent, which also generates autoreactive NKT
      cells.

PMID- 12061426
TI  - Complement activation by in vivo neonatal and in vitro extracorporeal membrane
      oxygenation.
AB  - Complment activation during extracorporeal membrane oxygenation (ECMO) in
      newborns can be caused by both the underlying disease processes and by blood
      contact with the ECMO circuit. We investigated the relative importance of these
      mechanisms by measuring C3a, C5a and sC5b-9 before, during and after neonatal
      ECMO in six consecutive newborn patients using enzyme-linked immunoassay. In
      addition complement activation during in vitro ECMO with repeated flow of the
      same blood volume was measured using blood from healthy adult donors. C3a
      increased significantly in vivo after 1 h (from 1035+/-193 to 1865+/-419
      microg/l) and in vitro ECMO (from 314+/-75 to 1962+/-1062 microg/l). C5a
      increased during ECMO without significant differences between in vivo and in
      vitro activation. In neonatal patients, sC5b-9 rose faster than in vitro, but the
      rapid increase was also significant for in vitro experiments (in vivo: from 328+/
      63 to 1623+/-387 microg/l after 2 h; and in vitro: from 78+/-32 to 453+/-179
      microg/l after 8 h). After this initial peak at 1-2 h, complement activation
      decreased gradually until 2-3 days after the initiation of ECMO. We conclude that
      in newborns the rapid activation of the complement system after the start of ECMO
      is predominantly caused by contact with artificial surfaces rather than the
      patient's underlying disease.

PMID- 12061427
TI  - Inhibitory effects of Spirulina in zymosan-induced arthritis in mice.
AB  - The anti-inflammatory effect of microalgae Spirulina was studied in zymosan
      induced arthritis in mice. Four days after the intra-articular injection of
      zymosan (15 mg/ml), Spirulina (100 and 400 mg/kg perorally) was administered to
      animals for 8 days. The mice were than killed and beta-glucuronidase was measured
      in the synovial fluid. Each knee joint was totally removed for histopathological
      studies. Spirulina significantly reduced the levels of beta-glucuronidase that
      had been increased by zymosan. Histopathological and ultrastructural studies
      showed inhibition of the inflammatory reaction, whereas no destruction of
      cartilage, well-preserved chondrocytes, and normal rough endoplasmic reticulum
      and mitochondria were seen. The anti-arthritic effect exerted by Spirulina as
      shown in this model may be at least partly due to the previously reported
      antiinflammatory and antioxidative properties of its constituent, phycocyanin. To
      our knowledge, this is the first report on the anti-inflammatory effect of
      Spirulina in an experimental model of arthritis.

PMID- 12061428
TI  - Role of histamine in the inhibitory effects of phycocyanin in experimental models
      of allergic inflammatory response.
AB  - It has recently been reported that phycocyanin, a biliprotein found in the blue
      green microalgae Spirulina, exerts anti-inflammatory effects in some animal
      models of inflammation. Taking into account these findings, we decided to
      elucidate whether phycocyanin might exert also inhibitory effects in the induced
      allergic inflammatory response and on histamine release from isolated rat mast
      cells. In in vivo experiments, phycocyanin (100, 200 and 300mg/kg post-orally
      (p.o.)) was administered 1 h before the challenge with 1 microg of ovalbumin (OA)
      in the ear of mice previously sensitized with OA. One hour later, myeloperoxidase
      activity and ear edema were assessed. Phycocyanin significantly reduced both
      parameters. In separate experiments, phycocyanin (100 and 200 mg/kg p.o.) also
      reduced the blue spot area induced by intradermal injections of histamine, and
      the histamine releaser compound 48/80 in rat skin. In concordance with the former
      results, phycocyanin also significantly reduced histamine release induced by
      compound 48/80 from isolated peritoneal rat mast cells. The inhibitory effects of
      phycocyanin were dose dependent. Taken together, our results suggest that
      inhibition of allergic inflammatory response by phycocyanin is mediated, at least
      in part, by inhibition of histamine release from mast cells.

PMID- 12061430
TI  - Levels of soluble ICAM-1 in premature and full-term neonates with infection.
AB  - BACKGROUND: Infection in the neonatal period is an extremely serious condition
      and diagnosis is difficult. C-reactive protein (CRP) is widely used as a marker
      of infection; however, its usefulness is limited in the early phase. The role of
      soluble intracellular adhesion molecule-1 (sICAM-1), an adhesion molecule, has
      been examined in recent studies as an early marker of neonatal infection with
      controversial results. AIM: Assessment of sICAM-1 concentrations and correlation
      with CRP, which is the currently used marker of infection, in order to use sICAM
      as an early diagnostic tool in neonates suspected for infection METHODS: Blood
      samples and blood cultures were obtained from two groups of pre-term and full
      term neonates with clinical suspicion of infection prior to the initiation of
      antibiotics. The sICAM-1 and CRP values were compared with the corresponding
      noninfected ones (n = 10 each). RESULTS: The sICAM-1 levels were found increased
      in the group of both premature and term neonates with infection compared with the
      corresponding healthy ones (P < 0.0001). Prematurity combined with infection
      resulted in excessive increase of the levels of sICAM-1 in comparison with full
      term infected newborns (p < 0.001). CRP values were normal in all samples except
      one in both full-term and premature infected neonates on day 1 of clinically
      suspected infection. Serial detection of CRP values on days 2 and 4 of infection
      revealed a pattern according to which CRP values in premature neonates continued
      rising, while in the group of full terms these values, after rising on the second
      day, lowered on day 4. CONCLUSIONS: Increased sICAM-1 levels can be detected
      early in both full-term and premature neonates with sepsis while CRP levels are
      within normal range at the same time. Assessment of sICAM-1 concentrations may be
      used as a diagnostic tool in neonates suspected for infection, resulting in
      earlier initiation of antibiotic therapy and therefore improving their outcome.

PMID- 12061429
TI  - Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated
      with elevated lipid peroxidation in patients with Behcet's disease.
AB  - AIM: Behcet's disease (BD) is asystemic immunoinflammatory disorder and the
      aetiopathogenesis is to be specified. Cytokines play a role in immune response
      and in many inflammatory diseases. The aim of this case-control study is to
      investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha,
      interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine
      IL-8 levels in patients with BD. We also determined the end product of lipid
      peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative
      stress. METHODS: A total of 37 patients (19 men, 18 women) with BD (active, n =
      17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects
      (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF
      alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a
      spectrophotometer technique using the immulite chemiluminescent immunometric
      assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines
      and lipid peroxidation in the active period were compared with the inactive
      period of the disease. Results are expressed as mean +/- standard error. RESULTS:
      IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all
      samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6
      (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in
      active BD patients were significantly higher than those in inactive patients
      (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p =
      0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or
      control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001;
      6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p <
      0.001, respectively). On the contrary, only the mean IL-6 level was significantly
      different between inactive BD and control subjects (p = 0.02). All acute phase
      reactants were significantly higher in active BD than in inactive period (for
      each, p < 0.01). CONCLUSIONS: High levels of sIL-2R, IL-6, IL-8 and TNF-alpha
      indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF
      alpha seem to be related to disease activity. Increased lipid peroxidation
      suggests oxidative stress in BD and therefore tissue damage in such patients.
      Amelioration of clinical manifestations would be envisaged by targeting these
      cytokines, chemokines and lipid peroxidation with pharmacological agents.

PMID- 12061431
TI  - Antitumor effect of Bothrops jararaca venom.
AB  - Many experimental studies have been carried out using snake venoms for the
      treatment of animal tumors, with controversial results. While some authors have
      reported an antitumor effect of treatment with specific snake venom fractions,
      others have reported no effects after this treatment. The aim of this study was
      to evaluate the effect of Bothrops jararaca venom (BjV) on Ehrlich ascites tumor
      (EAT) cells in vivo and in vitro. In the in vivo study, Swiss mice were
      inoculated with EAT cells by the intraperitoneal (i.p.) route and treated with
      BjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were
      evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and
      14th days. The survival time was also evaluated after 60 days of tumor growth. In
      the in vitro study, EAT and normal peritoneal cells were cultivated in the
      presence of different BjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80
      microg) and viability was verified after 3, 6, 12 and 24 h of cultivation.
      Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the
      5% level of significance. It was observed that in vivo treatment with BjV induced
      tumor growth inhibition, increased animal survival time, decreased mortality,
      increased the influx of polymorphonuclear leukocytes on the early stages of tumor
      growth, and did not affect the mononuclear cells number. In vitro treatment with
      BjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with
      higher effects against peritoneal cells. Taken together, our results demonstrate
      that BjV has an important antitumor effect. This is the first report showing this
      in vivo effect for this venom.

PMID- 12061432
TI  - Threat of foreign arthropod-borne pathogens to livestock in the United States.
AB  - There are many exotic animal pathogens throughout the world that, if introduced
      into the United States. could have a significant detrimental impact on the health
      of livestock, agricultural economy, the environment, and public health. Many of
      these pathogens are arthropod-borne and potential vectors are readily available
      in the United States. A number of these arthropod-borne pathogens are discussed
      here as examples that illustrate the potential risk and the consequences of
      inadvertent introductions. Several International agencies have a role in global
      surveillance and in controlling animal diseases should they begin to expand their
      range. The risk to the United States is considerable. We propose that the United
      States invest in the improved infrastructure needed to reduce the risk of foreign
      arthropod-borne pathogens. Current U.S. programs focus on the exclusion of
      pathogens through regulation of animal movements and products, surveillance,
      especially trained animal disease diagnosticians, research support, international
      cooperation and, should pathogens enter our country, the resources for their
      prompt eradication. We suggest that the United States needs to develop a
      comprehensive, updated strategic plan to assess all aspects of current and future
      requirements, objectives, and resources needed to protect its national interests.

PMID- 12061433
TI  - Influence of nonsystemic transmission on the epidemiology of insect borne
      arboviruses: a case study of vesicular stomatitis epidemiology in the western
      United States.
AB  - Nonsystemic transmission, where a pathogen is transmitted between infected and
      uninfected vectors without the vertebrate host becoming viremic, may provide an
      explanation for transmission in systems where the vertebrate hosts have been
      difficult to identify. This transmission pathway had been previously demonstrated
      for tick-borne viruses and bacteria, but the recent demonstration for Simulium
      and vesicular stomatitis virus is the first for a blood-feeding insect. The
      epidemiology of vesicular stomatitis viruses has been difficult to understand,
      and nonsystemic transmission may be important. We use mathematical formulations
      of the basic reproduction number, R(0), to compare systemic and nonsystemic
      transmission. The absence of a latent period before host infectiousness in
      nonsystemic transmission may allow a more rapid increase in prevalence in the
      biting flies early in the development of a new outbreak. Aggregation of flies
      between hosts and at favored feeding sites on hosts will be important, but
      further data on nonsystemic transmission as a function of space and time are
      required to fully assess this pathway. The data needed to compare the two
      pathways and their relative roles in virus epidemiology are discussed.

PMID- 12061435
TI  - New addition to the mosquito fauna of United States, Anopheles grabhamii
      (Diptera: Culicidae).
AB  - An anopheline mosquito new to the United States was collected in Monroe County,
      FL, USA. It is Anopheles (Anopheles) grabhamii Theobald, a species common
      throughout the Greater Antilles area and often found in association with
      Anopheles albimanus Wiedemann.

PMID- 12061434
TI  - Detection of Bartonella quintana from body lice (Anoplura: Pediculidae) infesting
      homeless people in Tokyo by molecular technique.
AB  - We report detection of Bartonella quintana Brenner, the pathogenic agent of
      trench fever, from body lice, Pediculus humanus L., infesting homeless people in
      Tokyo by polymerase chain reaction. Two of 12 (16.7%) homeless were infested with
      Bartonella-positive body lice. From the current status of the recent increase of
      homeless people in many large cities of the developed countries, a medical
      examination of homeless people should be carefully performed in the consideration
      of trench fever. Sampling of body lice from clothing of homeless people is
      recommended for quick and accurate diagnosis of trench fever through the
      detection of B. quintana DNA.

PMID- 12061436
TI  - Histochemical localization of N-acetyl-galactosamine in the midgut Lutzomyia
      longipalpis (Diptera: Psychodidae).
AB  - The binding of lectins to the midgut of the female sand fly Lutzomyia longipalpis
      (Lutz & Neiva) was investigated using lectin-gold conjugates. Midguts from
      laboratory-reared flies provided fructose solution and/or blood fed on hamster
      were dissected at 6, 24, and 48 h and at 5 and 7 d after feeding. Before
      examination by transmission electron microscopy, each midgut was sectioned,
      incubated with lectins from four sources (Canavalia ensiformis [ConA], Helix
      pomata agglutinin [HPA], peanut agglutinin [PNA], and wheat germ agglutinin [WGA]
      ), then conjugated with colloidal gold. Only HPA, which is specific for N-acetyl
      galactosamine (GalNAc), bound to the midgut. Binding sites were cytoplasmic
      secretory granules and microvilli throughout the length of the midgut epithelium.
      Binding occurred in sand flies fed fructose as well as in flies receiving a blood
      meal. The presence of GalNAc on the midgut microvilli of sand flies before,
      during, and after blood feeding indicates this amino-sugar is not altered by
      digestion. As a structural component, GalNAc may represent a terminal on a
      receptor molecule. The failure of the sand fly peritrophic matrix to bind WGA by
      N-acetylglucosamine may be caused by the complex composition of the membrane,
      which renders N-glycan inaccessible to the lectin-gold conjugate.

PMID- 12061437
TI  - Feeding behavior of Lutzomyia pseudolongipalpis (Diptera: Psychodidae), a
      putative vector of visceral leishmaniasis in Venezuela.
AB  - Lutzomyia pseudolongipalpis Arrivillaga & Feliciangeli is the first new sand fly
      species in the L. longipalpis species complex that has been formally described
      since it was separated by genetic as well as by morphological characters. It is
      the putative vector of the American visceral leishmaniasis in La Rinconada,
      Curarigua, a restricted focus in central western Venezuela. We investigated the
      feeding behavior of this species. The blood meals from 210 of 429 (48.9%)
      engorged females caught by CDC light traps were identified by a dot enzyme-linked
      immuno-absorbent assay using antisera against humans and common domestic animals.
      We propose a new index, the host selectivity index, which is the number of sand
      flies fed on a given host relative to the available biomass of that host, as an
      indicator of the feeding behavior of this phlebotomine sand fly. The host
      selectivity index is compared with the forage ratio, which is the percentage of
      sand flies fed on a given host by the percentage which that host represented in
      the total census of available animals and humans. The most attractive animal for
      L. pseudolongipalpis in Curarigua was the dog, whereas humans were shown to be
      relatively unattractive. However, not only selectivity or biomass, but also the
      accessibility to this host may have influenced these results. The low population
      density of dogs and the low accessibility of L. pseudolongipalpis to humans in
      relation to domestic animals might help to explain the sporadic transmission of
      visceral leishmaniasis in this focus.

PMID- 12061438
TI  - Anopheles sacharovi (Diptera: Culicidae): a reemerging malaria vector in the
      Ararat Valley of Armenia.
AB  - In 1994, the first indigenous case of malaria since the 1960s was reported in
      Armenia, and the number of cases quickly increased in the ensuing years. In 1998,
      a roll-back malaria program was developed to eliminate the recently established
      foci of malaria infection and to prevent the reestablishment of malaria in
      Armenia. As part of this program, we carried out entomological surveys to
      identify the potential malaria vectors in the Ararat Valley, the area where most
      of the indigenous malaria cases had been reported. In particular, we attempted to
      ascertain the presence of Anopheles sacharovi Favre, which is historically the
      most important malaria vector in Armenia yet which had not been reported since
      1965. In 1998-2000, we collected adult mosquitoes and larvae in the city of Masis
      and in three rural villages of the Ararat Valley. Species identification of the
      members of the Anopheles maculipennis complex was performed through egg and
      larval morphology, heteroduplex analysis, and sequencing of the second internal
      transcribed spacer of ribosomal DNA. Two species of the complex were identified:
      An. sacharovi, found in all of the study sites, andAn. maculipennis s.s. Meigen,
      the most common species in the area. The reemergence of An. sacharovi in the
      study sites shows that the receptivity for malaria is still high in the Ararat
      Valley and, likely, in other regions of Armenia.

PMID- 12061439
TI  - Impact of habitat degradation on phlebotominae (Diptera: Psychodidae) of tropical
      dry forests in Northern Colombia.
AB  - We examined changes in the phlebotomine fauna resulting from human intervention
      in a tropical dry forest of Northern Colombia where visceral and cutaneous
      leishmaniases are endemic. A natural forest reserve (Coloso) and a highly
      degraded area (San Andres de Sotavento [SAS]) were sampled monthly for 8 mo using
      Shannon traps, sticky traps, and resting-site collections. Overall abundances
      were higher in Coloso (15,988) than in SAS (2,324). and species richness of
      phlebotomines was greater in the forest reserve (11 species) than in the degraded
      habitat (seven species). Fisher alpha, a measure of diversity, reinforced this
      trend. Both sand fly communities were dominated by Lutzomyia evansi (Nuoez
      Tovar), vector of Leishmania chagasi (Cunha & Chagas), representing 92 and 81% of
      all captures in Coloso and SAS, respectively. Lutzomyia longipalpis (Lutz &
      Neiva), the common vector of visceral leishmaniasis, accounted for 4-7% of the
      sand fly community. Lutzornyia panamensis (Shannon) and Lutzomya gomezi
      (Nitzulescu), putative vectors of Leishmania braziliensis (Vianna), had low
      abundances at both study sites. The zoophilic species Lutzomyia cayennensis
      (Floch & Abonneuc) and Lutzomyia trinidadensis (Newstead) were present in
      variable numbers according to trapping methods and site. Habitat degradation
      negatively affected sand fly communities, but medically important species were
      able to exploit modified environments, thereby contributing to Lishmania
      endemicity.

PMID- 12061440
TI  - Toxic effect of aliphatic alcohols against susceptible and permethrin-resistant
      Pediculus humanus capitis (Anoplura: Pediculidae).
AB  - The effectiveness of 1-octanol, 1-nonanol, 1-decanol, 1-undecanol, and 1
      dodecanol was evaluated by immersion method against susceptible and permethrin
      resistant head lice, Pediculus humanus capitis De Geer, from Buenos Aires,
      Argentina. All the tested alcohols showed knockdown effect at 10 min and
      mortality 18 h after treatment. The highest activity was found for the 1
      dodecanol (KC50 2.55%, LC50 2.28%) and the lowest for 1-octanol (KC50 8%, LC50
      4.46%). The toxicity to the head lice systematically increased with the increase
      in carbon atoms in the n-aliphatic alcohol moiety, and with the octanol:water
      coefficient (r2 = 0.94). The pediculicidal activity of 1-dodecanol was not
      correlated with resistance to permethrin, because no significant difference was
      observed between toxicity parameters in the susceptible (MAR) and the permethrin
      resistant populations which had different resistant levels (RR 5.77 x for E49
      population, RR 9.5 x for HL population and RR > 35.3 x for GH population). The
      pediculicidal effect of aliphatic alcohols demonstrated in this study and the
      lack of correlation with the permethrin resistance may prove to have a practical
      value for use in susceptible and permethrin-resistant head lice control.

PMID- 12061441
TI  - Investigation of the aedes (Stegomyia) flavopictus complex (Diptera: Culicidae)
      in Japan by sequence analysis of the internal transcribed spacers of ribosomal
      DNA.
AB  - Aedes (Stegomyia) flavopictus Yamada is widely distributed in Japan and Korea.
      The species comprises three subspecies based on current morphological taxonomy:
      Aedes flavopictus in the Palearctic region of Japan, Ae. f downsi Bohart & Ingram
      from Amami and Okinawa Islands, and Ae. f miyarai Tanaka, Mizusawa & Ingram from
      Ishigaki and Iriomote Islands of the Ryukyu Archipelago. These subspecies
      designations are based on observations of a combination of several morphological
      characters, none of which, by itself is diagnostic for discriminating among the
      three subspecies. To further study the relationships in this group, we examined
      the nucleic acid sequence divergence in the internal transcribed spacer regions
      (ITSI and ITS2) of the ribosomal DNA gene array of Ae. flavopictus individuals
      collected at five sites from three geographic regions in Japan. Analysis of
      sequence data by distance and maximum parsimony methods produced phylogenetic
      trees that showed separation of the specimens into three major clades,
      corresponding to both subspecies and geographic region. These results were
      consistent with and support the current classification and geographic
      distribution of the three subspecies.

PMID- 12061442
TI  - Point source inoculation of mesocyclops (Copepoda: Cyclopidae) gives widespread
      control of Ochlerotatus and Aedes (Diptera: Culicidae) immatures in service
      manholes and pits in north Queensland, Australia.
AB  - This study details the novel application of predacious copepods, genus
      Mesocyclops, for control of Ochlerotatus tremulus (Theobald) group and Aedes
      aegypti (L.) mosquito larvae in subterranean habitats in north Queensland,
      Australia. During June 1997, 50 Mesocyclops sp. 1 were inoculated into one
      service manhole in South Townsville. Wet season rainfall and flooding in both
      1998 and 2000 was responsible for the dispersal of copepods via the underground
      pipe system to 29 of 35 manholes over an area of 1.33 km2. Significant reductions
      in Aedes and Ochlerotatus larvae ensued. In these habitats, Mesocyclops and
      Metacyclops were able to survive dry periods, when substrate moisture content
      ranged from 13.8 to 79.9%. At the semiarid inland towns of Hughenden and
      Richmond, cracking clay soil prevents drainage of water from shallow service pits
      where Oc. tremulus immatures numbered from 292-18,460 per pit. Introduction of
      Mesocyclops copepods into these sites during May 1999 resulted in 100% control of
      Oc. tremulus for 18 mo. One uninoculated pit subsequently became positive for
      Mesocyclops with resultant control of mosquito larvae.

PMID- 12061443
TI  - Factors influencing sperm transfer and insemination in cat fleas (Siphonaptera:
      Pulicidae) fed on an artificial membrane system.
AB  - Sperm transfer through the epididymis, a prerequisite for insemination of cat
      fleas, Ctenocephalides felis (Bouche) was stimulated by exposure of unfed male
      fleas to juvenile hormone III residues for 3 d at 25 degrees C or exposure of
      unfed fleas to 37 degrees C for 6 d. Sperm transfer was completed at least three
      times faster in unfed males held at 37 degrees C than in those held at 25 degrees
      C. Although percentage sperm transfer in fleas fed water or 0.15 M saline at 37
      degrees C was not significantly increased over that of unfed fleas, a
      significantly greater percentage of blood-fed males completed sperm transfer at
      2, 3, and 6 d. At least two factors influenced insemination: exposure of fleas to
      host body temperature and amount of food consumption. When blood-fed males and
      females were paired and fed 0.15 M saline, 0% were inseminated at 25 degrees C
      versus 35% at 37 degrees C. Because percentage insemination did not increase in
      blood-fed males and females that were paired and fed 0.15 M saline at 37 degrees
      C for an additional 48 h, continuous bloodfeeding appeared to be required for
      maximal rates of mating and insemination. Furthermore, no females were
      inseminated when blood-fed males and females were paired at 37 degrees C and
      starved. Treatment of unfed fleas with juvenile hormone III did not substitute
      for bloodfeeding in stimulating mating and insemination; when blood-fed males
      were paired with JH III-treated females and vice versa and fed 0.15 M saline at
      37 degrees C, 0% were inseminated. However, when fleas were fed 0.15 M saline and
      exposed to 1,250 ppm juvenile hormone III or fed whole blood and exposed to 12.5,
      125, or 1,250 ppm juvenile hormone III, percent insemination was significantly
      increased in comparison to the controls. Therefore, juvenile hormone secretion in
      blood-fed fleas may regulate mating success indirectly by stimulating sperm
      transfer.

PMID- 12061444
TI  - Experimental transmission of eastern equine encephalitis virus by Ochlerotatus j.
      japonicus (Diptera: Culicidae).
AB  - We evaluated the potential for Ochlerotatus j. japonicus (Theobald), a newly
      recognized invasive mosquito species in the United States, to transmit eastern
      equine encephalitis (EEE) virus. Aedes albopictus (Skuse) and Culex pipiens (L.)
      were similarly tested for comparison. Ochlerotatus j. japonicus and Ae.
      albopictus became infected and transmitted EEE virus by bite after feeding on
      young chickens 1 d after they had been inoculated with EEE virus (viremias
      ranging from 10(7.0-8.7) plaque-forming units [PFU]/ml of blood). No Cx. pipiens
      (n = 20) had detectable levels of virus 14 d after feeding on an EEE-virus
      infected chicken with a viremia of 10(8.1) PFU per ml of blood. Depending on the
      viral titer in the donor chicken, infection rates ranged from 55-100% for Oc. j.
      japonicus and 93-100% for Ae. albopictus. In these two species, dissemination
      rates were identical to or nearly identical to infection rates. Depending on the
      viral titer in the blood meal, estimated transmission rates ranged from 15 to 25%
      for Oc. j. japonicus and 59-63% for Ae. albopictus. Studies of replication of EEE
      virus in Oc. j. japonicus showed that there was an "eclipse phase" in the first 4
      d after an infectious blood meal, that viral titers peak by day 7 at around
      10(5.7) per mosquito, and that virus escaped the mid-gut as soon as 3 d after the
      infectious blood meal. These data, combined with the opportunistic feeding
      behavior of Oc. j. japonicus in Asia and the reported expansion of its range in
      the eastern United States, indicate that it could function as a bridge vector for
      EEE virus between the enzootic Culiseta melanura (Coquillett)-avian cycle and
      susceptible mammalian hosts.

PMID- 12061445
TI  - Geographical information systems and bootstrap aggregation (bagging) of tree
      based classifiers for Lyme disease risk prediction in Trentino, Italian Alps.
AB  - The risk of exposure to Lyme disease in the province of Trento, Italian Alps, was
      predicted through the analysis of the distribution of Ixodes ricinus (L.) nymphs
      infected with Borrelia burgdorferi s.l. with a model based on bootstrap
      aggregation (bagging) of tree-based classifiers within a geographical information
      system (GIS). Data on L ricinus density assessed by dragging the vegetation in
      438 sites during 1996 were cross-correlated with the digital cartography of a
      GIS, which included the variables altitude, exposure and slope, substratum,
      vegetation type and roe deer density. Ticks were more abundant at altitudes below
      1,300 m a.s.l., in the presence of limestone and vegetation cover with
      thermophile deciduous forests and high densities of roe deer. A bootstrap
      aggregation procedure (bagging) was used to produce a model for the prediction of
      tick occurrence, the accuracy of which was tested on actual tick counts assessed
      by a further dragging campaign carried out during 1997 to determine infection
      prevalence and resulted in average 77%. Other tests of the model were made on
      additional and independent data sets. The prevalence of infection with Borrelia
      burgdorferi s.l, determined by polymerase chain reaction on 2,208 nymphs
      collected by random dragging in 245 transects selected within eight areas where
      the model predicted the occurrence of I. ricinus during 1997, was 17.5% and was
      positively correlated to tick abundance and roe deer density. These findings were
      used to relate the output of the bagged model (probability of tick occurrence) to
      the density of infected nymphs through a stepwise model selection procedure and
      thus to produce a GIS digital map of the probability distribution of infected
      nymphs in the Province of Trento at high resolution scale (50 by 50-m cell
      resolution). The application of the bagging procedure increased the accuracy of
      the prediction made by a single classification tree, a well-known classification
      method for the analysis of epidemiological data.

PMID- 12061446
TI  - Integrated control of peridomestic larval habitats of Aedes and Culex mosquitoes
      (Diptera: Culicidae) in atoll villages of French Polynesia.
AB  - An integrated larval mosquito control program was carried out in Tiputa village
      on Rangiroa atoll of French Polynesia. Mosquito abundance before and after
      treatment was compared with the abundance in an untreated village. Mosquito
      larval habitats consisted of large concrete or polyurethane cisterns, wells, and
      200-liter drums. Depending on the target species, larval habitat category, its
      configuration, and purpose (drinking consumption or not), abatement methods
      consisted of sealing the larval habitats with mosquito gauze, treating them with
      1% Temephos, covering the water with a 10-cm thick layer of polystyrene beads or
      introducing fish (Poecillia reticulata Rosen & Bailey). All premises of the
      chosen village were treated and a health education program explained basic
      mosquito ecology and the methods of control. A community health agent was trained
      to continue the control program at the end of the experiment. Entomological
      indices from human bait collections and larval surveys indicated that mosquito
      populations were reduced significantly, compared with concurrent samples from the
      untreated control village, and that mosquito control remained effective for 6 mo
      after treatment. Effects of the treatment were noticed by the inhabitants in
      terms of a reduction in the number of mosquito bites. In the Polynesian context,
      such control programs may succeed in the long-term only if strong political
      decisions are taken at the village level, if a community member is designated as
      being responsible for maintaining the program, and if the inhabitants are
      motivated sufficiently by the mosquito nuisance to intervene.

PMID- 12061447
TI  - Chronological age-grading of house flies by using near-infrared spectroscopy.
AB  - The sensitivity and accuracy of near-infrared spectroscopy (NIRS) was compared
      with that of the pteridine fluorescence technique for estimating the
      chronological age of house flies, Musca domestica (L.). Although results with
      both techniques were significantly correlated with fly age, confidence limits on
      predicted ages generally were smaller with NIRS. Young flies could be readily
      differentiated from old flies by using NIRS. Age predictions using the pteridine
      method are dependent upon size, sex, and temperature at which adult flies are
      exposed. In contrast, those factors do not need to be determined for age-grading
      using NIRS. Classification accuracy using the NIRS method was similar for whole
      flies, fresh heads, dried heads, and ethanol-preserved heads. The NIRS method was
      also suitable for predicting age of stable flies, Stomoxys calcitrans (L.), and
      face flies, Musca autumnalis De Geer. NIRS has several advantages over the
      measurement of pteridine levels for age-grading field-collected flies, including
      speed and portability of instrumentation, and not needing to determine sex, size,
      and temperatures to which adult flies were exposed.

PMID- 12061448
TI  - Protection against lyme disease spirochete transmission provided by prompt
      removal of nymphal Ixodes scapularis (Acari: Ixodidae).
AB  - Public health recommendations for Lyme disease prevention generally include daily
      tick checks and prompt removal of attached ticks as a means of decreasing the
      risk of acquiring Lyme disease in highly endemic regions. In the current study,
      we determined whether crushing nymphal ticks during removal with forceps
      increased the risk of B. burgdorferi transmission, what degree of protection from
      transmission of B. burgdorferi was provided by removal of nymphal Ixodes
      scapularis Say at specific intervals, and whether commercial devices marketed for
      tick removal worked when tested against nymphal I. scapularis. Both removal via
      gentle pressure (26% transmission) or crushing the tick (30% transmission) caused
      a significant decrease in transmission as compared with the sham control (70%
      transmission). The degree of protection provided via tick removal decreased
      steadily up to 60 h of attachment; between 60 and 66 h, a dramatic falloff in
      protection occurred to the point where no protection was observed at 66 h.
      Finally, commercial tick removal devices varied widely in their efficacy for the
      removal of attached nymphal I. scapudaris.

PMID- 12061449
TI  - Strategies for the management of resistance in mosquitoes to the microbial
      control agent Bacillus sphaericus.
AB  - Bacillus sphaericus (B.spi) strain 2362 has been recognized as a promising
      mosquito larvicide, and various preparations of this strain have been tested and
      used in mosquito control programs worldwide. This control agent has advantages of
      high efficacy, specificity, persistence, and environmental safety. However,
      resistance in Culex pipiens complex mosquitoes to Bsph has occurred in both
      laboratory and field populations, necessitating development of resistance
      management strategies. Studies were initiated aiming at reversing previously
      established Bsph resistance in a laboratory colony of Culex quinque fasciatus Say
      by selections with Bti alone, Bti and Bsph in rotation, or mixture. Partial
      restoration of susceptibility to Bsph was achieved by selection of resistant
      colony for 10 generations with Bti alone at LC80). After this colony was switched
      back to Bsph selection for 20 generations, resistance to Bsph partially increased
      to a stable level. Selections of Basph-resistant colonies with Bti and Bsph in
      rotation or mixture resulted in steady decline of resistance over 30 generations,
      with rapid decline in resistance noted in the initial 10-15 generations. It is
      interesting to note that selections with Bti and Bsph in rotation increased
      susceptibility to Bti in Bsph-resistant colony. It is promising that selection
      with Bti alone, Bsph and Bti in rotation, or mixture have a potential for
      developing practical strategies to overcome acquired resistance to Bsph in Cx.
      quinquefasciatus populations.

PMID- 12061450
TI  - Efficiency of Leptotrombidium chiggers (Acari: Trombiculidae) at transmitting
      Orientia tsutsugamushi to laboratory mice.
AB  - Thirteen different laboratory colonies of Leptotrombidim chiggers [L.
      chiangraiensis Tanskul & Linthicum, L. deliense Walch and L. imphalum (Vercammen
      Grandjean &Langston)] were evaluated for their ability to transmit Orientia
      tsutsugamushi (Hyashi) to mice. Of 4,372 transmission attempts using individual
      chiggers from all 13 colonies, 75% (n = 3,275) successfully infected mice.
      Transmission rates for the individual chigger colonies ranged from 7 to 80%.
      Increasing the number of chiggers that fed on a given mouse generally increased
      transmission rates. Transmission of O. tsutsugamushi to mice by different
      generations (F1-F11) of certain chigger colonies was stable; however,
      transmission rates varied greatly in other colonies. Transmission rates (both
      vertical and horizontal) of several L. changraiensis colonies and the L. deliense
      colony were the highest, suggesting that these colonies may be useful for the
      development of a chigger-challenge model that can be used to evaluate the
      efficacy of candidate scrub typhus vaccines or therapeutic agents in laboratory
      mice.

PMID- 12061451
TI  - Bifenthrin: a useful pyrethroid insecticide for treatment of mosquito nets.
AB  - Bifenthrin, a pyrethroid insecticide already used in agriculture was evaluated in
      laboratory conditions against susceptible and pyrethroid resistant mosquitoes, as
      a potential insecticide for treatment of mosquito nets. Two laboratory strains of
      Anopheles gambiae s.s. Giles, the major malaria vector in Africa, and two of
      Culex quinquefasciatus Say, a major pest mosquito in urban areas, were used.
      Compared with other pyrethroids such as permethrin and deltamethrin, the
      intrinsic toxicity of bifenthrin, measured by topical application with
      susceptible strains, was intermediate. By forced tarsal contact on filter papers
      (cylinder tests) or on netting materials (cone tests), bifenthrin was found
      slightly more effective against A. gambiae than against C. quinquefasciatus, in
      terms of mortality and knock-down effect. With free flying mosquitoes (tunnel
      tests), bifenthrin was very efficient in killing mosquitoes and inhibiting blood
      feeding. Against the two pyrethroid resistant strains, bifenthrin was relatively
      efficient against A. gambiae but the impact of resistance was greater with C.
      quinquefasciatus. In tunnel tests, blood feeding remained almost entirely
      inhibited with the two species despite resistance. The high mortality of
      susceptible mosquitoes and excellent blood feeding inhibition of susceptible and
      resistant strains makes bifenthrin a good candidate for treatment of netting
      materials, particularly in areas where C. quinquefasciatus, the main nuisance in
      urban areas, is resistant to pyrethroids. The slower knock-down and lower
      irritant effect also makes this insecticide especially attractive when a mass
      killing effect on mosquito populations is expected.

PMID- 12061453
TI  - Field evaluation of repellent formulations against daytime and nighttime biting
      mosquitoes in a tropical rainforest in northern Australia.
AB  - Field trials to compare repellent formulations containing either picaridin or
      deet against rainforest mosquitoes in northern Queensland, Australia, were
      conducted. Three repellents were compared at night: 9.3% picaridin and 19.2%
      picaridin (Autan Repel and Autan Repel Army 20, respectively, Bayer, Sydney,
      Australia) and 35% deet in a gel (Australian Defense Force [ADF]). During the
      day, the following three repellents were compared: 19.2% picaridin, 20% deet in a
      controlled release formulation (Sawyer Controlled Release Deet), and 33% deet in
      a polymer formulation (U.S. Army Extended Duration Topical Insect and Arthropod
      Repellent [EDTIAR]). The predominant mosquito species collected was Verrallina
      lineata (Taylor), with smaller numbers of Ochlerotatus kochi (Donitz), Anopheles
      farauti s.s. Laveran, Ochlerotatus notoscriptus (Skuse), and Coquilletidia
      xanthogaster (Edwards). In nighttime tests, 19.2% picaridin provided >94.7%
      protection for at least 9 h, and ADF deet provided >95% protection for 7 h. The
      9.3% picaridin formulation provided >95% protection for only 2 h, and provided
      60% protection at 9 h. In daytime tests, Sawyer 20% deet provided >95% protection
      for 6 h, and both 19.2% picaridin and U.S. Army EDTIAR provided >95% protection
      for 8 h. In both nighttime and daytime tests 19.2% picaridin provided similar or
      better protection than deet formulations.

PMID- 12061452
TI  - Rickettsiella-like bacteria in Ixodes woodi (Acari: Ixodidae).
AB  - We examined a parthenogenetic strain of the hard tick Ixodes woodi Bishopp for
      the presence of endosymbiotic bacteria. Electron microscopic examination revealed
      the ovarian tissues and Malpighian tubules were infected with pleomorphic
      bacteria. Two basic types were observed: a larger granular cell and a smaller
      condensed cell. Cloning and sequence analysis of polymerase chain reaction (PCR)
      amplified 16S rRNA gene yielded a single sequence from bacteria present in I.
      woodi tissues. Phylogenetic analysis of the nearly complete 16S rDNA indicated
      that the ticks were infected with an endosymbiont belonging to the gamma
      subdivision of the Proteobacteria. It clustered with the insect pathogenic
      species Rickettsiellagrylli (Vago and Martoja 1963) and the animal pathogen
      Coxiella burnetii (Derrick 1939) Philip 1948. Our results suggest that the I.
      woodi females harbored a single endosymbiotic bacterium related to selected
      Rickettsiella species and to C burnetii.

PMID- 12061454
TI  - Mating alters the cuticular hydrocarbons of female Anopheles gambiae sensu
      stricto and aedes Aegypti (Diptera: Culicidae).
AB  - The cuticular hydrocarbons of female Anopheles gambiae Giles sensu stricto and
      Aedes aegypti (L.) mosquitoes were analyzed before and after they mated. In An.
      gambiae, the proportions of the two cuticular hydrocarbon components, n
      heneicosane and n-tricosane, were significantly reduced as the female aged and
      after it mated. There were no changes in the hydrocarbon composition of males
      after they mated. Hydrocarbon extracts from mated and unmated An. gambiae females
      as well as those from males caused a reduction in the rates of female
      insemination when they were applied to unmated females. Female Ae. aegypti showed
      significant changes in the proportions of n-heptadecane, n-pentacosane and n
      hexacosane in their cuticles after mating. These data suggest that cuticular
      hydrocarbons may play some role in chemical communication during mosquito
      courtship.

PMID- 12061455
TI  - Acari ectoparasites of bats from Minas Gerais, Brazil.
AB  - Ectoparasites were recovered from Brazilian bats captured from April to November
      1997 at or near Parque Estadual do Rio Doce, State of Minas Gerais, southeastern
      Brazil. Sixty bats were collected, representing three families and 13 species.
      Five Acari families were recorded: Myobiidae, Trombiculidae, Labidocarpidae,
      Macronyssidae, and Spinturnicidae. The macronyssid Radfordiella desmodi Radovsky
      (71 specimens) and the spinturnicid Periglichrus iheringi Oudemans (45 specimens)
      were the most abundant mite species. They were mainly recorded on Desmodus
      rotundus (Geoffroy) and Artibeus litratus (Ofers), respectively. Among
      trombiculid chiggers, the genus Colicus Brennan (55 specimens) was predominant
      and found mainly on Carollia perspicillata (L.). The current study presents new
      data about host-parasite relationships and increases the understanding of
      geographical distribution for some mite and chigger species.

PMID- 12061456
TI  - Naturally occurring mixed infection of Plasmodium vivax VK210 and P. vivax VK247
      in anopheles mosquitoes (Diptera: Culicidae) in western Thailand.
AB  - We report the natural co-infection of a single Anopheles mosquito with Plasmodium
      vivax Grassi & Feletti phenotypes VK210 and VK247. In total, 8,452 anopheline
      mosquitoes collected between June 1999 and July 2001 were tested by ELISA for the
      presence of circumsporozoite (CS) protein to VK210, VK247, and P. falciparum
      (Welch) (PF). A total of 29 species was represented; however, the predominant
      species tested were A. minimus Theobald (4,632), A. sawadwongporni
      Rattanarithikul & Green (1,248), A. maculatus Theobald (1,201), A. campestris
      Reid (478), and A. barbirostris Van der Wulp (391). A total of 17 positive
      mosquitoes was identified by ELISA, and included the following: A. minimus
      infected with VK210 (5), PF (3), and both VK210 and VK247 (1), A. maculatus
      infected with VK210 (1), VK247 (1), and both VK210 and VK247 (1), A. campestris
      infected with VK210 (2), A. sawadwongporni infected with VK247 (1) and PF (1),
      and A. hodgkini Reid infected with VK247 (1). This is the first report of a
      single mosquito naturally infected with both VK210 and VK247.

PMID- 12061457
TI  - Prosthetic heart valves.

PMID- 12061458
TI  - Which medications should be held before a pharmacologic or exercise stress test?

PMID- 12061459
TI  - A young man with hyperthermia and new-onset seizures.

PMID- 12061460
TI  - Drug smuggling raises medical and legal issues.

PMID- 12061461
TI  - Educating travelers about malaria: dealing with resistance and patient
      noncompliance.
AB  - Malaria is a risk to travelers in many parts of the world. Physicians need to
      tailor chemoprevention strategies to take into account resistance patterns.
      Patient education is important, especially for those travelers least likely to
      comply with prevention strategies. Most travelers who contract malaria do not
      become ill until they return home, so recognition and treatment are crucial.

PMID- 12061462
TI  - Patient information. Protecting yourself against malaria.

PMID- 12061463
TI  - Idiopathic dilated cardiomyopathy: a common but mystifying cause of heart
      failure.
AB  - While researchers try to elucidate the origins of idiopathic dilated
      cardiomyopathy, clinicians continue to face the challenges of identifying and
      treating the causes of this condition to improve symptoms and survival. We review
      classification schemes for dilated cardiomyopathy and the current range of
      diagnostic and therapeutic options and treatment goals.

PMID- 12061464
TI  - Women and headache: a treatment approach based on life stages.
AB  - Effective headache management in women requires an understanding of the unique
      epidemiologic and pathophysiologic factors affecting women. We present
      preventive, abortive, and nonpharmacologic approaches to headache treatment that
      vary with the chronologic and hormonal stages of a woman's life, with special
      attention to headache during pregnancy and later in life.

PMID- 12061465
TI  - Update on kidney transplantation: increasing clinical success, expanding waiting
      lists.
AB  - Short-term and long-term renal allograft survivals have improved in recent years
      for several reasons. Improvements in immunosuppression have reduced acute
      cellular rejections to about 15% to 25%. The use of erythropoietin to treat
      anemia allows patients to avoid transfusions, thereby reducing sensitization and
      hyperacute rejections. Advances in the management of cardiovascular disease and
      infection have also been significant factors in improved patient and allograft
      survival. Although living donations are helping to increase the number of
      transplants, their effect on rapidly growing waiting lists is relatively small.

PMID- 12061466
TI  - Intensive care update: seven studies that should change your practice.
AB  - Seven recent studies in intensive care found that: *The need for intravenous
      sedation should continually be reassessed * Low-dose dopamine does not offer
      significant renal protection * Higher doses of continuous venovenous
      hemofiltration may improve survival * Subclavian central venous catheterization
      is associated with fewer complications than the femoral route * We have little
      evidence to support the use of ranitidine and sucralfate as prophylaxis for
      stress ulcers * Many young patients with suspected bacterial meningitis can
      undergo lumbar puncture without a CT scan if they have no abnormalities on a
      quick history and physical examination * Intensive insulin therapy to control
      blood glucose lowers the mortality rate.

PMID- 12061467
TI  - Diagnosis in rehabilitation: woolly thinking and resource inequity.
AB  - The diagnostic process in rehabilitation has traditionally been termed
      assessment. However the goals of assessment are no different to the goals of
      diagnosis in traditional medical practice. The purpose is, in both instances, to
      acquire sufficient information to understand the cause(s) of the presenting
      problem(s), to allow more-or-less specific intervention(s) to be undertaken and,
      where appropriate, to allow a prognosis to be given. The main difference is that
      in rehabilitation the presenting problems are limitations in activities and the
      main items investigated are impairment and contextual matters, whereas in
      medicine the presenting problems are symptoms, and the goals are the diagnosis
      and treatment of the underlying disease. Unfortunately it is commonly assumed
      that rehabilitation diagnosis is simple and unimportant. Consequently few
      resources are allocated by purchasers to the process of making a rehabilitation
      diagnosis, in comparison to the huge resources devoted to achieving disease
      diagnosis.

PMID- 12061468
TI  - Therapeutic electrical stimulation to improve motor control and functional
      abilities of the upper extremity after stroke: a systematic review.
AB  - BACKGROUND: Therapeutic electrical stimulation (TES) is a therapeutic strategy
      aimed at improving impairments of the upper extremity in stroke. OBJECTIVE:
      Assessment of the available evidence on the effect of TES of the affected upper
      extremity in improving motor control and functional abilities after stroke.
      METHODS: A systematic literature search was performed to identify randomized
      controlled trials (RCTs) that have studied the effect of TES on motor control and
      functional abilities. The methodological quality of the studies was assessed
      systematically by two raters. The reported outcomes were examined to evaluate the
      effect of TES and to identify a possible relationship with patient
      characteristics, method of stimulation and methodological quality. When possible,
      effect sizes were calculated (Hedges' g). RESULTS: Six RCTs were included. The
      methodological scores ranged from 7 to 16 (maximum 19). All studies assessed the
      effect on motor control, and four reported a positive effect. Effect sizes
      calculated in three studies ranged from 0.55 to 1.46. Only two studies assessed
      the effect on functional ability, one reported a positive effect. Subgroup
      analyses in two studies suggest a better response to stimulation in less severely
      affected patients. Apart from this, no relationship between effect and patient
      characteristics, method of stimulation or methodological quality could be
      detected. CONCLUSIONS: The present review suggests a positive effect of
      electrical stimulation on motor control. No conclusions can be drawn with regard
      to the effect on functional abilities.

PMID- 12061469
TI  - Evaluation of a home-based exercise and training programme to improve sit-to
      stand in patients with chronic stroke.
AB  - OBJECTIVE: To investigate the feasibility and efficacy of a task-specific home
      based exercise protocol for improving sit-to-stand (STS), with additional
      exercises to strengthen lower limb extensor muscles in patients with chronic
      stroke. DESIGN: A pre-test, post-test design was used. SUBJECTS: Six subjects at
      least one year post stroke and discharged from all rehabilitation services for at
      least six months participated in the study. OUTCOME MEASURES: Functional
      performance of sit-to-stand was evaluated using the Standing Up item of the Motor
      Assessment Scale (MAS). Peak vertical ground reaction force, walking speed over
      10 m and grip strength were also measured. RESULTS: Group MAS score was
      significantly higher at post-test than at pre-test with two subjects reaching the
      highest point on the scale and three subjects reaching the second highest point.
      Time-to-peak vertical ground reaction force occurred significantly closer to
      thighs-off, the critical time when the body mass is propelled into standing.
      Walking speed increased significantly over 10 m from a mean of 0.86 m/s to 1.10
      m/s. Grip strength, which was not trained, did not change. CONCLUSIONS: This
      study demonstrates that a home-based task-specific exercise and training protocol
      for STS can induce improved performance of STS and increase walking speed more
      than one year after stroke.

PMID- 12061470
TI  - Hypnotic imagery as a treatment for phantom limb pain: two case reports and a
      review.
AB  - OBJECTIVE: To provide a theoretical background, to review existing literature and
      to present new case material relevant to the treatment of phantom limb pain using
      hypnotic imagery. METHOD: This paper presents two new case reports involving the
      use of hypnotic imagery procedures in the alleviation of phantom limb pain and
      reviews 10 previous clinical studies which have involved a similar approach. The
      earlier studies were identified by electronic and manual searches of the relevant
      literature. RESULTS: Two main treatment strategies can be identified: (1)
      ipsative/imagery-based approaches and (2) movement/imagery-based approaches. A
      common finding is the need to treat the phantom limb as a 'real' body part, to
      accept its existence as a valid mental representation and to avoid treating the
      amputation stump as the sole source of the phantom pain sensations. CONCLUSION:
      Hypnotic procedures appear to be a useful adjunct to established strategies for
      the treatment of phantom limb pain and would repay further, more systematic,
      investigation. Suggestions are provided as to the factors which should be
      considered for a more systematic research programme.

PMID- 12061471
TI  - Intramuscular neurolysis with alcohol to treat post-stroke finger flexor
      spasticity.
AB  - OBJECTIVE: To evaluate the effectiveness of intramuscular neurolysis with alcohol
      for the treatment of finger flexor spasticity in individuals with stroke. DESIGN:
      Case series. SETTING: Outpatient clinic of a tertiary rehabilitation facility.
      SUBJECTS: Thirty patients with a mean age of 60.2 years and post-stroke duration
      of 8.3 months with finger flexor spasticity. INTERVENTIONS: Intramuscular
      neurolysis or motor point blocks of the finger flexors of the hemiplegic upper
      extremity with 50% ethyl alcohol. MAIN OUTCOME MEASURES: The severity of
      spasticity as measured by the Modified Ashworth Scale (MAS) and the passive range
      of motion of the proximal interphalangeal joints of the second to fifth digits.
      RESULTS: The mean baseline MAS score was 4.0 +/- 0.5 and this improved to 2.0 +/-
      0.6, 2.2 +/- 0.6 and 2.6 +/- 0.6 at four weeks, three months and six months post
      neurolysis respectively. The gains in range of motion were 18.5 +/- 6.7, 17.5 +/-
      6.4 and 14.9 +/- 4.8 degrees at four weeks, three months and six months post
      neurolysis respectively. These improvements were statistically significant (p <
      0.05). Two subjects developed temporary dysesthetic pain of the forearm and palm.
      CONCLUSION: Intramuscular neurolysis with alcohol provides good relief of finger
      flexor spasticity in hemiplegic individuals.

PMID- 12061472
TI  - The Action Research Arm Test: is it necessary for patients being tested to sit at
      a standardized table?
AB  - OBJECTIVE: To validate results obtained from using the Action Research Arm Test
      (ARAT) at tables of a common height for persons who have experienced a stroke.
      DESIGN: Each subject was tested three times with the ARAT while sitting at three
      different tables: a table specially designed for the test and two generally
      available tables similar in height to the standard table. The patients were
      randomly and equally assigned to three different raters and to three different
      tables in accordance with a counterbalanced design. All evaluations were
      completed within a two-day period. SUBJECTS: Sixty-one patients who had had only
      one stroke (mean age 63.3 years; median time since stroke onset 81 days; mean
      ARAT score administered at the standard table 33.8) participated in this study.
      RESULTS: The intraclass correlation coefficient (ICC) for the total scores
      obtained using the ARAT at the different tables was 0.99, indicating very high
      agreement. The ICCs were also very high in each of the subscales. CONCLUSION: The
      results of this study support the use of the ARAT at ordinary tables roughly
      similar in height to that specially designed for use with the ARAT.

PMID- 12061473
TI  - How comparable are tests of apraxia?
AB  - OBJECTIVE: To compare commonly used tests for the diagnosis of apraxia. MEASURES:
      People with unilateral left hemisphere lesions, diagnosed with apraxia, were
      compared in their scoring on commonly used tests for apraxia (n = 17). SETTING:
      Rivermead Rehabilitation Centre, Oxford, England, a specialist inpatient
      neurological unit. RESULTS: Production moment correlations were low, or did not
      reach significance level between three tests for ideomotor apraxia (r = 0.46 p <
      0.05 one-tailed test, r = 0.005 NS, r = -0.23 NS, df = 15). Six of the seventeen
      apraxic patients scored above cut-off point on one test, but below cut-off point
      on others, indicating that commonly used tests for apraxia may not be reliable
      for diagnosis if used singly. Internal consistency within tests was also variable
      (Cronbach's alpha 0.72, 0.85, 0.85). CONCLUSION: The commonly used tests for
      apraxia may identify different people as 'apraxic', possibly by eliciting
      different aspects of apraxia and identifying potential subtypes of the condition.
      The use of multiple tests is, therefore, recommended in order to identify people
      with apraxia. The need for repeat reliability studies for apraxia assessments,
      together with a search for a 'gold standard' test is apparent.

PMID- 12061474
TI  - Sensitivity of the Tinetti Gait Assessment for detecting change in individuals
      with Parkinson's disease.
AB  - OBJECTIVE: To determine the Tinetti Gait Assessment's sensitivity for detecting
      changes in verbally instructed gait in patients with Parkinson's disease. DESIGN:
      Two-group comparison study with sample of convenience. SETTING: Motor Behavior
      Lab, Department of Physical Therapy, University of Florida. SUBJECTS: Twenty
      community-dwelling, elderly adults: 10 with moderately disabling Parkinson's
      disease (PD) recruited from local Parkinson Support Groups and 10 gender- and age
      matched adults without PD recruited from the local community. MAIN OUTCOME
      MEASURES: Tinetti Gait Assessment (TGA) overall scores. All subjects were
      assessed while walking under five verbally instructed conditions: (1) usual
      walking, (2) swing arms, (3) take large steps, (4) walk fast, (5) count aloud.
      RESULTS: A 2 x 5 analysis of variance (group x instructional set) was performed.
      The PD group scored less than the control group on the TGA regardless of the
      instructed walking conditions (p < 0.05), however, there was no significant
      difference in the TGA scores across conditions. The effect size of the
      instructional set measured by the TGA was greatest for the swing arms condition,
      though small at 0.25. CONCLUSION: The TGA is not sensitive for detecting change
      in the gait impairments observed in moderately disabling PD and, therefore, is
      not adequate as an assessment to establish short-term goals, guide treatment, or
      assess the effects of intervention for clients with PD.

PMID- 12061475
TI  - Early discharge and home rehabilitation after hip fracture achieves functional
      improvements: a randomized controlled trial.
AB  - OBJECTIVE: To compare hospital and home settings for the rehabilitation of
      patients following hip fracture. DESIGN: Randomized controlled trial comparing
      accelerated discharge and home-based rehabilitation (n = 34) with conventional
      hospital care (n = 32) for patients admitted to hospital with hip fracture.
      SETTING: Three metropolitan hospitals in Adelaide, Australia. SUBJECTS: Sixty-six
      patients with fractured hip. INTERVENTIONS: Patients assigned to the home-based
      rehabilitation group were discharged within 48 hours of randomization. The
      project team therapists made visits to the patient's home and negotiated a set of
      realistic, short-term and measurable treatment goals with both the patient and
      carer. Those randomized to usual care remained in hospital for conventional
      rehabilitation. MAIN OUTCOME MEASURES: Physical and social dependence, balance
      confidence, quality of life, carer strain, patient and carer satisfaction, use of
      community services and incidence of adverse events such as re-admission and
      falls. RESULTS: While there was no difference between the groups for all measures
      of quality of life, patients in the accelerated discharge and home-based
      rehabilitation group recorded a greater improvement in MBI from randomization (p
      < 0.05) and scored higher on the Falls Efficacy Scale (p < 0.05) at four months.
      There was no difference in falls rates. Patients in the home-based rehabilitation
      group had a shorter stay in hospital (p < 0.05) but a longer stay in
      rehabilitation overall (p < 0.001). The groups were comparable on the rate and
      length of admissions after discharge, use of community services, need for carer
      input and contact with general practitioner (GP) after discharge. CONCLUSIONS:
      This trial further supports the practice of accelerated discharge from hospital
      and home-based rehabilitation in selected patients recovering from hip fracture.
      Such a practice appears to improve physical independence and confidence in
      avoiding subsequent falls which may have implications for longevity and overall
      quality of life.

PMID- 12061476
TI  - A comparative study of Mini-Mental Test, Clock Drawing task and Cognitive-FIM in
      evaluating functional outcome of elderly hip fracture patients.
AB  - OBJECTIVE: To compare the clock drawing task with other cognitive tests used for
      the prediction of discharge functional outcome, in elderly hip fracture patients.
      DESIGN: Cohort study. SETTING: A department of geriatric-orthopaedic
      rehabilitation of a tertiary hospital. PATIENTS: One hundred and forty-three
      consecutive patients undergoing inpatient comprehensive rehabilitation following
      hip fracture. MEASUREMENTS: Cognitive status was assessed by the Clock Drawing
      Task, Mini-Mental State Examination (MMSE) and the Cognitive-FIM (cognFIM).
      Functional status outcome was evaluated by the Functional Independence Measure
      (FIM), using absolute and relative parameters of efficacy and efficiency.
      RESULTS: Correlation coefficients (Pearson correlation) between the three
      cognitive tests resulted in values ranging from 0.607 to 0.732 (p < 0.001).
      Similar correlation coefficients were observed for all cognitive tests when
      correlated with relative efficacy and efficiency outcome parameters (p < 0.001),
      but not with absolute outcome parameters. CONCLUSIONS: Clock Drawing Test is
      similar to Mini-Mental and Cognitive-FIM with respect to the evaluation of
      functional status outcome following rehabilitation of hip fractures. The similar
      correlations with functional outcome parameters as well as the simplicity of
      administration favour the use of either Clock Drawing Task or MMSE in the initial
      assessment of elderly patients with hip fractures.

PMID- 12061477
TI  - Co-morbidity adjustment for functional outcomes in community-dwelling older
      adults.
AB  - OBJECTIVE: To characterize relationships between self-reported co-morbidity and
      functional outcomes in community-dwelling older adults, and to assess whether the
      impact of co-morbidity persists even after adjustment for baseline functional
      status. DESIGN: Prospective observational study. We examined associations between
      self-reported co-morbidity at baseline and functional outcomes at one year, with
      and without adjustment for baseline functional status. SETTING: Outpatient
      clinics at a managed care and a Veterans Affairs site. SUBJECTS: Four hundred and
      fifty-seven community-dwelling older adults representing a broad spectrum of
      overall health status. MAIN OUTCOME MEASURES: (a) New basic ADL (activities of
      daily living) problem during follow-up; (b) 10-point decline in the physical
      function index of the MOS-36 (MOS-PFI). RESULTS: Co-morbidity was associated with
      adverse functional outcomes in bivariable analyses. After adjustment for age and
      baseline functional status, an accumulated co-morbidity score provided additional
      explanatory power for predicting new ADL problems; odds ratios were 2.30 (1.09,
      5.09) and 2.96 (1.48, 6.25) for 2 and > or = 3 affected co-morbidity domains,
      respectively. The impact of baseline status was also important; odds ratios for
      new ADL problems were 4.77 (2.68, 8.81) when at least one instrumental activity
      of daily living (IADL) problem was present at baseline, and 15.6 (8.05, 31.3)
      when at least one basic ADL problem was present at baseline. CONCLUSIONS:
      Accumulated self-reported co-morbidity has significant negative effects on
      function at one year; these effects are attenuated but not eliminated by
      adjustment for baseline status. Co-morbidity adjustment is probably an important
      design element in clinical research focused on functional outcomes in older
      adults.

PMID- 12061478
TI  - Difficulties associated with wrist disorders--a qualitative study.
AB  - OBJECTIVE: To explore the range of functional difficulties and compensatory
      mechanisms reported by individuals with a wrist disorder, to provide a basis for
      development of a patient-focused outcome instrument. DESIGN: Descriptive study
      using a qualitative, interview-based framework. SETTING/SUBJECTS: A volunteer
      sample of individuals, who were diagnosed with a unilateral, localized wrist
      disorder, were recruited from a wide range of health care settings situated in
      different socio-economic and geographic areas of Adelaide, Australia. Recruitment
      continued until theoretical saturation of the data occurred. INTERVENTIONS: Semi
      structured, audiotaped interviews were conducted with each individual to elicit
      information concerning 'how your wrist disorder has affected your ability to
      perform daily activities'. MAIN OUTCOME MEASURES: Trends regarding reporting of
      difficult activities and compensatory mechanisms used. RESULTS: Forty-two
      individuals were interviewed. This was the point where theoretical saturation of
      research information had been reached. A few individuals reported difficulty with
      functional tasks prior to wrist injury. Following diagnosis, a wide range of
      difficulties, which included heavy, gross and fine motor activities, was
      reported. Compensatory mechanisms were used by all individuals, with requesting
      someone else to do the task, using the other hand, and using other parts of the
      body to lift or grasp being the most common. CONCLUSIONS: Current wrist outcome
      instruments do not contain the full range of difficult activities that were
      elicited from our sample, which casts doubt on these instruments' ability to
      fully measure change in capacity. Our results should provide the basis for the
      development of a relevant, sensitive, patient-focused outcome instrument.

PMID- 12061479
TI  - Development and implementation of the Rehabilitation Activities Profile for
      children: impact on the rehabilitation team.
AB  - OBJECTIVE: To describe the changes in functioning of the rehabilitation team
      induced by the Rehabilitation Activities Profile for children (Children's RAP),
      an instrument designed to improve interdisciplinary communication in paediatric
      rehabilitation. DESIGN: Multiple case-study design. SUBJECTS: Seven paediatric
      rehabilitation teams. INTERVENTION: A two-year project to develop and implement
      the Children's RAP. DATA COLLECTION: During the project, data were gathered from
      observations, documents and informal interviews. After the project, formal
      interviews were held with team members and parents, and a focus group meeting
      with representatives of the teams was organized. DATA ANALYSIS: Data were
      analysed by the method of analytic induction. The analysis was checked by an
      independent researcher. The preliminary results and conclusions were discussed in
      detail with participating teams. RESULTS: Development and implementation, as well
      as the changes induced by the project, varied between teams. Changes were
      observed for individual team members, for the team as a whole and for the
      children and their parents. However, changes for individual team members occurred
      relatively quickly, in comparison with the other changes. To achieve an optimal
      interdisciplinary team approach all changes are necessary. Therefore, we
      postulated four hierarchical steps in the development of an interdisciplinary
      team approach: (1) process-oriented approach, (2) result-oriented approach, (3)
      problem-oriented approach, and (4) interdisciplinary team approach. CONCLUSION:
      It took a considerable amount of time to achieve the interdisciplinary team
      approach by implementing the Children's RAP. However, the first steps are not
      only rewarding in themselves, but also prerequisites for further improvement.

PMID- 12061480
TI  - Measuring perceived activity limitations in lower extremity Complex Regional Pain
      Syndrome type 1 (CRPS I): test-retest reliability of two questionnaires.
AB  - OBJECTIVE: To assess the test-retest reliability of two questionnaires for
      measuring activity limitations in patients with Complex Regional Pain Syndrome
      type 1 (CRPS I) of the lower extremity. DESIGN: Patients filled out the Walking
      Stairs Questionnaire and the Questionnaire Rising and Sitting Down twice during a
      one-week period. SETTING: Outpatient pain clinic of a university hospital.
      PATIENTS: Twenty-one outpatients with CRPS I of the lower extremity. RESULTS: The
      Walking Stairs Questionnaire and the Questionnaire Rising and Sitting Down were
      reliable in terms of test-retest reliability as expressed by Spearman's r (range
      0.79-0.90 and 0.85-0.89 respectively) and the ICC (range 0.78-0.84 and 0.84-0.87
      respectively). CONCLUSION: Both questionnaires form a reliable tool for measuring
      activity limitations of patients with CRPS I of a lower extremity.

PMID- 12061481
TI  - What is the impact of genetic counselling in women at increased risk of
      developing hereditary breast cancer? A meta-analytic review.
AB  - Meta-analytic methods were used to determine the impact of genetic counselling on
      women with a family history of breast cancer. Published studies with prospective
      designs and randomized controlled trials were included in the review, and the
      psychological outcomes assessed were generalized psychological distress,
      generalized anxiety, depression, and breast cancer anxiety. Other outcomes
      investigated were the accuracy of perceived risk of developing breast cancer,
      breast cancer genetics knowledge and breast cancer screening uptake. A meta
      analysis was performed to estimate effect size, where sufficient data were
      available. A total of 12 studies, most of which measured several outcomes, met at
      least one of the inclusion criteria. A sufficiently large number of studies were
      available to assess the magnitude of effects on three outcomes: generalized
      psychological distress, generalized anxiety and accuracy of perceived risk of
      developing breast cancer. The quantitative synthesis showed that genetic
      counselling leads to statistically significant decreases in generalized anxiety,
      with an average weighted effect sizes of r = - 0.17 (p<0.01). In contrast, the
      reduction in psychological distress exhibited a trend towards statistical
      significance only, with r = -0.074 (p = 0.052). The impact of genetic counselling
      on the accuracy of perceived risk was associated with an effect size of r = 0.56
      (p<0.01). Thus in this meta-analysis, we demonstrated the efficacy of genetic
      counselling in meeting two of its objectives: reducing women's anxiety levels and
      improving the accuracy of their perceived risk. This review highlighted that most
      research so far focused on generalized distress and anxiety and accuracy of
      perceived risk, to the exclusion of other, perhaps equally important, types of
      outcomes. Future studies are likely to lead to more comprehensive assessments if
      additional emotional, cognitive and behavioural outcomes are included in the
      assessment.

PMID- 12061482
TI  - Challenges of citizen participation in regional health authorities.
AB  - Citizen participation has been included as part of health reform, often in the
      form of lay health authorities. In Canada, these authorities are variously known
      as regional health boards or councils. A set of challenges is associated with
      citizen participation in regional health authorities. These challenges relate to:
      differences in opinion about whether there should be citizen participation at
      all; differences in perception of the levels and processes of participation;
      differences in opinion with respect to the roles and responsibilities of health
      authority members; differences in opinion about the appropriate composition of
      the authorities; differences in opinion about the requisite skills and attributes
      of health authority members; having a good support base (staff, good information,
      board development); understanding and operationalizing various roles of the board
      (governance and policy setting) versus the board staff (management and
      administration); difficulties in ensuring the accountability of the health
      authorities; and measuring the results of the work and decisions of the health
      authorities. Despite these challenges, regional health authorities are gaining
      support as both theoretically sound and pragmatically based approaches to health
      system reform. This review of the above challenges suggests that each of the
      concerns remains a significant threat to meaningful public participation.

PMID- 12061483
TI  - Adherence to highly active antiretroviral therapies (HAART) in HIV-infected
      patients: from a predictive to a dynamic approach.
AB  - To-date, most socio-behavioural research about HTV-infected patients' adherence
      to highly active antiretroviral therapies (HAART) has been based on cross
      sectional studies. The French APROCO cohort gave us the opportunity to conjointly
      analyse the relationships between short-term adherence to HAART and HIV-infected
      patients' characteristics before initiation of treatment on the one hand, factors
      related to patients' subjective experience with HAART on the other hand. At the
      fourth-month follow-up visit (M4) after first prescription of HAART (M0), 26.7%
      of our sample of 445 patients self-reported non-adherence behaviour. Some
      patients' characteristics at M0 (younger age, poor housing conditions, lack of
      social support, and problems of adherence with previous antiretroviral regimens)
      were related to non-adherence at M4 in multivariate analysis. Non-adherence at M4
      was, however, also related to the evolutions that affected a number of factors
      between M0 and M4: levels of depression, symptoms associated with treatment side
      effects, perception of individual state of health, beliefs towards effectiveness
      and toxicity of HAART. increases in alcohol and tobacco consumption, as well as
      contacts with other physicians than hospital HAART prescribers. Our prospective
      study brings additional evidence that even short-term non-adherence cannot be
      reliably predicted on the sole basis of a few a priori patient characteristics
      that clinicians could easily identify before initiation of HAART. It suggests
      that a dynamic approach to adherence, continuously monitoring the impact of
      experience with HAART on patients' daily lives, is needed for improving
      management of HIV/AIDS care.

PMID- 12061484
TI  - Youth homelessness in San Francisco: a life cycle approach.
AB  - HIV risk behaviors and seroprevalence are particularly high among street youth.
      Though many programs have been designed to serve them, street youth have low
      rates of service utilization. The aim of this street-based, ethnographic project
      was to study the social and cultural context of street life in this population.
      Data were collected by participant observation, exploratory interviews and semi
      structured interviews. Twenty street youth (15-23 years old; six female),
      recruited from street sites in San Francisco, participated in the interviews.
      Field notes and transcriptions were analyzed using an inductive technique for
      model building. This analysis yielded a proposed model of the life cycle of youth
      homelessness. In the first on the street stage, youth face an intense
      psychological feeling of outsiderness, and an urgency to meet basic needs. These
      stresses either lead to an escape from street life or to a process of
      acculturation to the street. Initiation to the street is facilitated by street
      mentors, who provide youth with survival skills. In the stasis stage, youth reach
      a tenuous equilibrium in which they can meet their basic needs. A strong street
      ethic allows youth to rationalize significant conflicts and frequent physical
      suffering. Youth in stasis are repeatedly thrown into disequilibrium, crises that
      frequently cause them to come into greater contact with mainstream society. After
      repeated episodes of disequilibrium, some youth extricate themselves from street
      life, finding a new identity in mainstream society. Otherwise, youth return to
      the street, in an episode of recidivism. The life cycle model suggests that
      street youth who are most open to intervention are those who are in transitional
      states, i.e., those who have just arrived on the street or those who are in
      crisis (disequilibrium). If this model is validated in a larger population of
      youth, programs that are aimed at these two stages in the life cycle could
      potentially effectively complement existing programs, which are usually focused
      on youth in stasis.

PMID- 12061486
TI  - Dynamics of change in local physician supply: an ecological perspective.
AB  - The purpose of this study is to employ an ecological framework to identify
      factors that have an impact on change in local physician supply within the USA. A
      particular specialty type of patient care physicians in a local market is defined
      as a physician population. Four physician populations are identified:
      generalists, medical specialists, surgical specialists, and hospital-based
      specialists. Based on population ecology theory, the proposed framework explains
      the growth of a particular physician population by four mechanisms: the intrinsic
      properties of this physician population; the local market's carrying capacity,
      which is determined by three environmental dimensions (munificence,
      concentration, diversity); competition within the same physician population; and
      interdependence between different physician populations. Data at the level of
      Metropolitan Statistical Areas (MSAs) were compiled from the US Area Resources
      File, the American Hospital Association Annual Surveys of Hospitals, the American
      Medical Association Census of Medical Groups, the InterStudy National HMO Census,
      and the US County Business Patterns. Changes in the number and percentage of
      physicians in a particular specialty population from 1985 to 1994 were regressed,
      respectively, on 1985-94 changes in the explanatory variables as well as their
      levels in 1985. The results indicate that the population ecology framework is
      useful in explaining dynamics of change in the local physician workforce.
      Variables measuring the three environmental dimensions were found to have
      significant, and in some cases, differential effects on change in the size of
      different specialty populations. For example, both hospital consolidation and
      managed care penetration showed significant positive eflects on growth of the
      generalist population but suppressing effects on growth of the specialist
      population. The percentage of physicians in a particular specialty population in
      1985 was negatively related to change in the size of that specialty population
      between 1985 and 1994, suggesting the existence of competition. Overall, the
      findings of this study facilitate a better understanding of the complexity of
      physician workforce supply.

PMID- 12061485
TI  - Neurolathyrism in Ethiopia: assessment and comparison of knowledge and attitude
      of health workers and rural inhabitants.
AB  - A cross sectional community based study was done in the Amhara Regional State of
      Ethiopia in 1999-2000 to assess and compare knowledge and attitude towards
      neurolathyrism among health workers and the rural community. A sample of 217
      health workers selected by probability proportional to size and randomly selected
      589 heads of household from a rural district were interviewed using pre-tested
      questionnaires. Neurolathyrism was widely known among the health workers and the
      community. More than half of community respondents associated the disorder with
      walking or lying on the straw and the stalks of grass pea. In a multivariate
      analysis. poor neurolathyrism knowledge among the community was associated with
      illiteracy and with presence of a neurolathyrism patient at home. Among health
      workers, contact with vapour or steam of grass pea foods was the commonest cause
      cited. In a multivariate analysis nurses had the poorest knowledge among the
      health workers. Depending on the subject, health workers and community
      respondents had more or less knowledge than the other. The prevailing recurrent
      adverse climatic conditions might promote grass pea as a 'friendly' crop to the
      poor peasants in marginal areas who otherwise rely on it only during times of
      food shortages and could increase the incidence of neurolathyrism. The poor
      knowledge among health workers and the community and the general neglect of
      neurolathyrism requires urgent intervention. Appropriate strategies for the
      dissemination of information education, and communication (IEC) are needed.

PMID- 12061487
TI  - Development of a 'communication disability model' and its implication on service
      delivery in low-income countries.
AB  - This paper argues that higher priority should be given to the development of
      services which support people with communication disabilities in low income
      countries and that these services should be different from those in other
      countries. Present services for this population group have poor coverage levels,
      tend to be centrally located and are orientated to specialist services. WHO
      (Health Programme Evaluation, Geneva, WHO, 1981) argue that health services
      should be based on meeting people's needs. This paper describes an analysis of
      'needs related' qualitative data concerning people with communication
      disabilities and their families in two low income countries and examines the
      results in relation to service development. The data was collected as part of
      five different studies concerning people with communication disabilities carried
      out in Uganda and Nigeria. Using the principles of established theory, these data
      helped develop, a theoretical model. This model is compared with WHO's
      classification of Impairment Disability and Handicap ICIDH-2 WHO (International
      Classification of Impairments Disabilities and Handicaps (ICIDH-2), A manual of
      classification relating to the consequences of diseases, Geneva, WHO. 1997a;
      1999). Suggestions are made as to how this model might inform planning and
      practice from the perspective of the five major stakeholder groups; government
      and non-government organizations, people with communication disabilities, their
      families and professionals. Consideration is also given as to how this theory can
      be used to strengthen existing services, or encourage a complete paradigm shift,
      with the creation of different services in new and innovative ways.

PMID- 12061488
TI  - One hundred and eighteen years of the German health insurance system: are there
      any lessons for middle- and low-income countries?
AB  - A number of low and middle income countries (LMICs) are considering social health
      insurance (SHI) for adoption into their social and economic environment or
      striving to sustain and improve already existing SHI schemes. SHI was first
      introduced in Germany in 1883. An analysis of the German system from its
      inception up to today may yield lessons relevant to other countries. Such an
      analysis, however, is largely lacking, especially with regard to LMICs. This
      paper attempts to fill this gap. For each of the following lessons, it considers
      if and under which conditions they may be of relevance to LMICs. First, small,
      informal, voluntary health insurance schemes may serve as learning models for
      fund administration and solidarity, but in order to achieve universal coverage
      government action is needed to formalise these schemes and to introduce a
      principle of compulsion. Once compulsory health insurance exists for some people,
      incremental expansion of coverage to other regions and social groups may be
      feasible to achieve universality. Second, in order to ensure sustainability of
      SHI, the mandated benefit package should be adapted incrementally in accordance
      with changing needs, values and economic circumstances. Third. in a pluralistic
      SHI system equity, as well as risk pooling and spreading, can be enhanced if
      funds merge. The optimal number of funds, however, will depend on the stage of
      development of the SHI system as well as on other objectives of the system,
      including choice and competition. A risk equalisation scheme may prevent the
      adverse effects of risk selection, if competition between insurance funds is
      introduced into the system. Fourth, as an alternative to both state and market
      regulation, self-governance may serve as a source of stability and sustainability
      as well as a means of decentralising and democratising a health care system.
      Finally, costs can be successfully contained in a fee-for-service system, if cost
      escalating provider behaviour is constrained by either political pressure or
      technical means.

PMID- 12061489
TI  - Change in job satisfaction, and its association with self-reported stress,
      cardiovascular risk factors and mortality.
AB  - Many studies have suggested that occupational stress may be related to the
      development of cardiovascular disease (CVD), independently of other known risk
      factors. Despite the recognition of job satisfaction as a particular form of
      stress, however, few studies have examined its association with CVD. Those
      studies that have explored the associations between job satisfaction and CVD risk
      factors, or job satisfaction and CVD mortality, have been largely cross-sectional
      in approach and report contradictory findings. This study revisits the
      associations between job satisfaction, self-reported stress. CVD risk factors and
      CVD mortality using longitudinal data from a cohort of working Scottish men and
      women recruited between 1970 and 1973. Approximately half of the cohort was
      screened for a second time, 4-7yr after the baseline examination. Job
      satisfaction at baseline was strongly associated with low or moderate perceived
      stress at 2nd screening. Men and women reporting decreased satisfaction in their
      jobs between baseline and 2nd screening tended to report moderate or high
      perceived stress at 2nd screening. Job satisfaction was associated with own
      occupational class in different directions for men and women. Men in the manual
      social classes reported more satisfaction with their jobs than their peers,
      whilst it was women in the non-manual social classes who reported more
      satisfaction with their jobs than their peers. There was limited evidence of an
      association between job satisfaction and age-adjusted CVD risk factors (diastolic
      blood pressure; blood cholesterol; body mass index; forced expiratory volume in
      1st amount of recreational exercise undertaken; cigarette smoking and alcohol
      consumption) for men, after adjustment for occupational class, but there was no
      evidence of any association for women. There was also no evidence to suggest that
      men or women reporting job dissatisfaction on one occasion or on two occasions
      several years apart, had a significantly greater risk of mortality from CVD.

PMID- 12061491
TI  - The fine art of critique.

PMID- 12061490
TI  - The contingent ranking method--a feasible and valid method when eliciting
      preferences for health care?
AB  - The Contingent Ranking Method--a feasible and valid method when eliciting
      preferences for health care? The objective of the study was to determine the
      feasibility and validity of the contingent ranking method, when eliciting
      preferences and measuring willingness to pay for health care. A measurement
      experiment based on ranking data is reported. Marginal willingness to pay for
      alleviation of rheumatoid arthritis symptoms that may be the outcome of a
      treatment with a novel anti-rheumatic agent, cA2 (now called TNF-alpha blockade)
      was calculated. The estimated marginal willingness to pay value was 650 DKK
      ($93). With regard to the health status variables and income variable the signs
      of the coefficients were, as expected, positive. The contingent ranking method is
      a feasible and valid method for eliciting preferences and determining willingness
      to pay estimates.

PMID- 12061492
TI  - Bioterrorism.

PMID- 12061493
TI  - Relationships of sexual abuse, connectedness, and loneliness to perceived well
      being in homeless youth.
AB  - ISSUES AND PURPOSE: To describe respondents' perceptions of connectedness,
      loneliness, and well-being; and to explore relationships among these variables.
      DESIGN AND METHOD: Survey data from 96 participants, focus group interviews with
      32 participants, and 10 individual interviews were analyzed. RESULTS: Sixty
      percent of the sample reported sexual abuse, which was significantly related to
      loneliness and inversely related to connectedness and perceived well-being.
      Subjects felt lonely and disconnected. They perceived their well-being in terms
      of current health status. PRACTICE IMPLICATIONS: High rates of sexual abuse, lack
      of connectedness, and loneliness may help to explain poor perceived well-being in
      homeless youth.

PMID- 12061494
TI  - The effects of infant feeding decisions on infant growth.
AB  - ISSUES AND PURPOSE: To determine the effects of feeding decisions on infant
      growth in the first 6 months of life. DESIGN AND METHODS: Growth measurements
      were collected twice during the first 6 months of infancy as part of a larger
      investigation of infant feeding practices (N = 52). RESULTS: Infants who received
      solid foods before the age of 4 to 6 months weighed less than those who received
      solid foods after 4 to 6 months. There were no differences in growth measurements
      between formula-fed and breast-fed infants, although breast-fed infants weighed
      more at birth. PRACTICE IMPLICATIONS: Emphasize the importance of feeding breast
      milk (preferably) or formula only for the first 6 months. Advise parents to
      withhold fruit juices until the infant is at least 6 months old.

PMID- 12061495
TI  - Identifying risk factors for maternal depression in families of adolescents with
      epilepsy.
AB  - ISSUES AND PURPOSE: To investigate factors associated with depressive symptoms in
      mothers of children with chronic seizure disorders. DESIGN AND METHODS: A cross
      sectional correlational design was used with a sample of 115 mother-child dyads
      in families where the child had chronic epilepsy. RESULTS: A three-factor model
      consisting of family income, satisfaction with family relationships, and presence
      of child behavior problems explained 32% of the variance in maternal depressive
      symptoms. PRACTICE IMPLICATIONS: Childhood epilepsy has a negative effect on the
      mother's mood in many families. Child behavior problems were found to be the
      strongest predictor of maternal depressive symptoms. Assessing for behavior
      problems and maternal depression should become a routine part of the family
      nursing assessment.

PMID- 12061496
TI  - Balancing high-tech nursing with holistic healing.

PMID- 12061497
TI  - Utilization of research via the Internet.

PMID- 12061498
TI  - Environment, mitochondria, and Parkinson's disease.
AB  - Parkinson's disease (PD) is a common and disabling neurodegenerative disease
      marked by progressive motor dysfunction, which results from selective
      degeneration of the nigrostriatal pathway. Epidemiological studies indicate that
      exposure to pesticides, rural living, farming, and drinking well water are
      associated with an increased risk of developing PD. Rare cases of PD are caused
      by mutations in nuclear genes, and there is increasing evidence for
      susceptibility genes that alter disease risk. Parkinson's disease is also
      associated with a systemic defect in mitochondrial complex I activity. Animal
      models indicate that exposure to inhibitors of mitochondrial complex I, including
      pesticides, is sufficient to reproduce the features of PD, but genetic factors
      clearly modulate susceptibility. Complex I defects may result in oxidative stress
      and increase the susceptibility of neurons to excitotoxic death. In this way,
      environmental exposures and mitochondrial dysfunction may interact and result in
      neurodegeneration.

PMID- 12061499
TI  - Remyelination within the CNS: do schwann cells pave the way for oligodendrocytes?
AB  - Schwann cells that have myelinated the CNS can be replaced by myelinating
      oligodendrocytes. It is unclear, however, why oligodendrocyte remyelination would
      occur for axons that are already myelinated. The Schwann cells might signal their
      own replacement by oligodendrocytes, but more probably a third player, the
      reactive astrocyte, is essential to this phenomenon. We propose that as long as
      reactive astrocytes do not form fibrous gliosis, they are beneficial to
      oligodendrocyte remyelination. Unknown is whether reactive astrocytes induce
      oligodendrocyte progenitor (NG2 immunopositive cells) cells to differentiate, a
      phenomenon that is absent in multiple sclerosis. So what role do Schwann cells
      play in CNS remyelination? They appear to serve to protect central axons and
      might coincidentally prevent reactive astrocytes from laying down scar tissue
      that impedes oligodendrocyte remyelination.

PMID- 12061500
TI  - Brain imaging studies of the functional organization of human olfaction.
AB  - It is believed that sensory functions are organized in a hierarchical and
      parallel manner. The sense of smell differs in several aspects from other senses:
      odors can immediately elicit emotional evocations, they are remembered after a
      long time, and they are difficult to label. This raises the question of whether
      odorous stimuli may be processed differently from the other sensory stimuli. New
      data from brain imaging studies suggest that this is not the case and that the
      specific characteristics of the sense of smell can be attributed to the
      engagement of limbic structures at an early stage in the signal processing.

PMID- 12061501
TI  - Mechanisms of hypoxic neurodegeneration in the developing brain.
AB  - Asphyxia and other insults to the developing brain are responsible for several
      human neurodevelopmental disorders. The pattern of neonatal brain injury differs
      from that seen in the adult nervous system, and there are wide differences in
      regional vulnerability. Recent evidence suggests that two events that contribute
      to this pattern of selective vulnerability are developmental changes in
      excitatory glutamate-containing neurotransmitter circuits and the propensity for
      immature neurons to die by apoptosis rather than necrosis. Developmental up
      regulation of NMDA receptors with enhanced function and increased expression of
      caspase-3 at critical periods in development are linked to these mechanisms.
      Although these molecular changes enhance the developing brain's capacity for
      plasticity by helping to prune redundant synapses and neurons, they can become
      "Achilles heels" in the face of a brain energy crisis.

PMID- 12061502
TI  - The cadherin family of cell adhesion molecules: multiple roles in synaptic
      plasticity.
AB  - Cadherins are cell adhesion molecules that are critically important for
      establishing brain structure and connectivity during early development. They are
      enriched at synapses and, by virtue of a number of properties including
      homophilic recognition and molecular diversity, have been implicated in the
      generation of synaptic specificity. Cadherins also participate in remodeling
      synaptic architecture and modifying the strength of the synaptic signal, thereby
      retaining an active role in synaptic structure, function, and plasticity, which
      extends beyond initial development. Cadherins have been implicated in the
      induction of long-term potentiation (LTP) of hippocampal synaptic strength, a
      cellular model for learning and memory. LTP is associated with the synthesis and
      recruitment of N-cadherin to newly forming synaptic junctions, induces molecular
      changes to N-cadherin indicative of augmented adhesive force, and can be
      prevented when cadherin adhesion is blocked. NMDA receptor activation, which is
      critically required for synaptic plasticity, may provide a signal that regulates
      the molecular configuration of synaptic N-cadherin, and therefore the strength of
      adhesion across the synaptic cleft. Additionally, there exists at the synapse a
      pool of surface cadherins that is untethered to the actin cytoskeleton and
      capable of a rapid and reversible dispersion along the plasmalemma under
      conditions of strong activity. These observations suggest that synaptic activity
      dynamically regulates both the strength and the localization of cadherin-cadherin
      bonds across the synaptic junctional interface, changes that may be crucial for
      regulating synaptic plasticity.

PMID- 12061503
TI  - Molecular adaptations for survival during anoxia: lessons from lower vertebrates.
AB  - Anoxia-tolerant neurons from several species of animals may offer unparalleled
      opportunities to identify strategies that might be employed to enhance the
      hypoxia or ischemia tolerance of vulnerable neurons. In this review, the authors
      describe how the response of hypoxia-tolerant neurons to limited oxygen supply
      involves a suite of mechanisms that reduce energy expenditure in concert with
      decreased energy availability. This response avoids energy depletion, excitotoxic
      neuronal death, and apoptosis. Suppression of ion channel functions, particularly
      those of the ionotropic glutamate receptors, is a response common in hypoxia
      tolerant neurons. The depression of excitability thereby achieved is essential
      given that the fundamental response to oxygen lack in anoxia-tolerant cells is a
      throttling down of metabolism to "pilot-light" levels. Many different types of
      processes have been found to down-regulate ion channel function. These include
      phosphorylation control, interactions with intracellular and extracellular ions,
      removal of active receptors from the neurolemma, and the direct sensing of oxygen
      by Na+ and K+ channels. Changes in [Ca2+]i may initiate a protective down
      regulation of many different pumps or channels. Transcriptional events leading to
      differential and/or decreased expression of receptors, proteins, and their
      subunits are probably very important but little studied.

PMID- 12061504
TI  - Retinal waves: implications for synaptic learning rules during development.
AB  - Neural activity is often required for the final stages of synaptic refinement
      during brain development. It is thought that learning rules acting at the
      individual synapse level, which specify how pre- and postsynaptic activity lead
      to changes in synaptic efficacy, underlie such activity-dependent development.
      How such rules might function in vivo can be addressed in the retinogeniculate
      system because the input activity from the retina and its importance in
      development are both known. In fact, detailed studies of retinal waves have
      revealed their complex spatiotemporal properties, providing insights into the
      mechanisms that use such activity to guide development. First of all, the
      information useful for development is contained in the retinal waves and can be
      quantified, placing constraints on synaptic learning rules that use this
      information. Furthermore, knowing the distribution of activity over the entire
      set of inputs makes it possible to address a necessary component of developmental
      refinement: rules governing competition between synaptic inputs. In this way, the
      detailed knowledge of retinal input and lateral geniculate nucleus development
      provides a unique opportunity to relate the rules of synaptic plasticity directly
      to their role in development.

PMID- 12061505
TI  - Ion regulation in the brain: implications for pathophysiology.
AB  - Ions in the brain are regulated independently from plasma levels by active
      transport across choroid plexus epithelium and cerebral capillary endothelium,
      assisted by astrocytes. In "resting" brain tissue, extracellular potassium
      ([K+]o) is lower and [H]o is higher (i.e., pHo is lower) than elsewhere in the
      body. This difference probably helps to maintain the stability of cerebral
      function because both high [K]o and low [H+]o enhance neuron excitability.
      Decrease in osmolarity enhances synaptic transmission and neuronal excitability
      whereas increased osmolarity has the opposite effect. Iso-osmotic low Na+
      concentration also enhances voltage-dependent Ca2+ currents and synaptic
      transmission. Hypertonicity is the main cause of diabetic coma. In normally
      functioning brain tissue, the fluctuations in ion levels are limited, but intense
      neuronal excitation causes [K+]o to rise and [Na+]o, [Ca2+]o to fall. When
      excessive excitation, defective inhibition, energy failure, mechanical trauma, or
      blood-brain barrier defects drive ion levels beyond normal limits, positive
      feedback can develop as abnormal ion distributions influence neuron function,
      which in turn aggravates ion maldistribution. Computer simulation confirmed that
      elevation of [K+]o can lead to such a vicious circle and ignite seizures,
      spreading depression (SD), or hypoxic SD-like depolarization (anoxic
      depolarization).

PMID- 12061506
TI  - Interleukin-6 (IL-6): a possible neuromodulator induced by neuronal activity.
AB  - IL-6 and its receptor(s) are found in the CNS in health and disease. Cellular
      sources are glial cells and neurons. Glial production of IL-6 has intensively
      been studied, but comparatively little is known about the induction of IL-6 in
      neurons. Emerging evidence suggests that IL-6 possesses neurotrophic properties.
      Recent data show that neuronal IL-6 expression is induced by excitatory amino
      acids or membrane depolarization. This implicates that IL-6 is produced not only
      under pathological conditions but may play a critical role as a physiological
      neuromodulator that is induced by neuronal activity and regulates brain
      functions. In the following article, the authors review the current data on IL-6
      expression in neurons, with special reference to the induction of IL-6 by
      neuronal activity. They discuss its direct and indirect effects as a
      neuromodulator and speculate about the possible function of IL-6 as a
      physiological regulatory molecule and as a neuroprotective agent in brain
      pathology.

PMID- 12061507
TI  - Inflammation, apoptosis, and Alzheimer's disease.
AB  - The pathophysiology of Alzheimer's disease (AD) involves the deposition of
      amyloid in the brain and the extensive loss of neurons. The mechanisms subserving
      neuronal death in the disease remain unclear, although it has been postulated
      that this is due to apoptosis. There is compelling evidence that inflammatory
      processes play a role in disease progression and pathology. Amyloid plaque
      deposition is accompanied by the association of microglia with the senile plaque,
      and this interaction stimulates these cells to undergo phenotypic activation and
      the subsequent elaboration of proinflammatory and neurotoxic products. This
      review focuses on the mechanisms by which neurons are lost in AD and the role
      microglial proinflammatory products play in neuronal death.

PMID- 12061508
TI  - The globus pallidus, deep brain stimulation, and Parkinson's disease.
AB  - Parkinson's disease (PD) is caused by the degeneration of the dopaminergic
      neurons in the substantia nigra. Loss of dopaminergic innervation leads to
      hyperactivity in the internal segment of the globus pallidus (GPi), the main
      output nucleus of the basal ganglia and to a profound disturbance in the function
      of motor circuits. Lesions of the GPi (or in its upstream modulator, the
      subthalamic nucleus) can greatly improve the motor symptoms of PD presumably by
      reducing this pathological activity. Paradoxically, high-frequency electrical
      stimulation of the GPi (deep brain stimulation, DBS) mimics the effects of
      pallidotomy and has become an accepted therapeutic technique. The mechanisms
      underlying the beneficial effects of pallidal DBS are not known. Various
      mechanisms that might account for inhibiting or disrupting the pathological
      pallidal outflow by high-frequency DBS have been proposed ranging from
      depolarization block to stimulation-evoked release of GABA, and these are
      discussed.

PMID- 12061509
TI  - Rural health research and rural health in the 21st century: the future of rural
      health and the future of rural health services research.
AB  - Rural health research is a unique field. It is neither a nested subcategory under
      general health services research nor a separate field of policy analysis or
      advocacy. Rural health research faces three potential crises: of content, of
      applicability, and of credibility. The content of the field is driven often by
      funds, its applicability is thus limited by its purview as well as its special
      constituency, and its credibility is challenged by its findings, sometimes
      contrary to accepted positions in the larger health services field. Rural health
      research can strengthen its position by accepting the paradoxes it presents,
      especially the paradox of continuing disparity in the face of substantial
      investment to eliminate differences, and by seeking to answer why this occurs
      across the rural-urban spectrum. Rural health research can answer questions about
      why the distribution of resources is unfair without depending solely on pure
      definitions

PMID- 12061510
TI  - Effect of medicare payment on rural health care systems.
AB  - Medicare payments constitute a significant share of patient-generated revenues
      for rural providers, more so than for urban providers. Therefore, Medicare
      payment policies influence the behavior of rural providers and determine their
      financial viability. Health services researchers need to contribute to the
      understanding of the implications of changes in fee-for-service payment policy,
      prospects for change because of the payment to Medicare+Choice risk plans, and
      implications for rural providers inherent in any restructuring of the Medicare
      program. This article outlines the basic policy choices, implications for rural
      providers and Medicare beneficiaries, impacts of existing research, and
      suggestions for further research. Topics for further research include
      implications of the Critical Access Hospital program, understanding how changes
      in payment to rural hospitals affect patient care, developing improved formulas
      for paying rural hospitals, determining the payment-to-cost ratio for physicians,
      measuring the impact of changes in the payment methodology used to pay for
      services delivered by rural health clinics and federally qualified health
      centers, accounting for the reasons for differences in historical Medicare
      expenditures across rural counties and between rural and urban counties,
      explicating all reasons for Medicare+Choice plans withdrawing from some rural
      areas and entering others, measuring the rural impact of proposals to add a
      prescription drug benefit to the Medicare program, and measuring the impact of
      Medicare payment policies on rural economies.

PMID- 12061511
TI  - Medicaid and rural health care.
AB  - The impact of Medicaid policies on systems of rural health care has typically
      been understood in terms of payment methods and rates. But Medicaid agencies have
      multifaceted influences, including service funding, promotion of access and
      quality, and infrastructure. We present in this article a general framework to
      explore these facets and examine literature that has attempted to identify and
      measure the impacts of the Medicaid program on rural health care systems. While
      the literature is relatively sparse, there is evidence that rural health systems
      have been both bolstered and challenged by Medicaid policies in several areas.
      Several contemporary developments in Medicaid, including increased state
      flexibility, uneven coverage expansion, and aggressive Medicaid purchasing
      strategies, suggest that tensions between Medicaid policy and rural health care
      needs could grow in the future. These tensions provide focus for developing a
      research agenda that explores the intersection of Medicaid and rural concerns; a
      number of research questions that would be a part of this agenda are presented.

PMID- 12061512
TI  - Quality of care in the rural context: a proposed research agenda.
AB  - The quality of health care provided in rural areas is critical to rural patients
      and providers and will shape the future evolution of the rural health care
      system. Past research has focused almost exclusively on disease-specific
      comparisons of the quality of care rendered in rural as compared with urban
      areas, which ignores the fact that it is the functioning of the entire system of
      care that determines whether or not rural residents receive high quality care.
      Future research should focus on the functioning of the entire rural system of
      care. To accomplish this objective, we suggest investments in the following
      areas: the creation of a national database that collects information on the
      process and outcome of care delivered to rural populations, the incorporation of
      human factors research into our research agenda, greater emphasis on the
      importance of sociodemographic and cultural issues to the quality of care, and a
      shift to a focus on populations as opposed to individuals.

PMID- 12061513
TI  - Rural public health: policy and research opportunities.
AB  - Changes in the health care system, medicine, and technology as well as in the
      characteristics of rural communities raise issues that impact the responsiveness
      of the rural public health system to emerging threats to health. These issues,
      which are systemic in nature and primarily involve the infrastructure of public
      health, include the capacity of rural public health to manage population health,
      utilize information technology, monitor performance of the essential public
      health functions, develop leadership and the public health workforce, and promote
      the interaction and integration of public health and health care. This article
      provides an overview of policy and research implications, and it suggests that
      each of these issues contributes to the capacity of public health to effectively
      improve the outcomes of health in rural communities.

PMID- 12061514
TI  - Rural hospitals: trends, challenges, and a future research and policy analysis
      agenda.
AB  - Previous reviews of the status of rural hospitals conclude that rural hospitals
      play a major role in ensuring the provision of health services in rural areas,
      are an essential part of the social and economic identity of rural communities,
      have had mixed success in their ability to respond to environmental threats, and
      are very sensitive to public policies due, in part, to their small size. The
      evolving hospital paradigm in the United States and a turbulent economic and
      health care environment have created an uncertain future for the rural hospital.
      Hospitals are being forced to shift their emphasis from filling acute inpatient
      care beds to providing a more diversified set of services through linkages with
      other institutions and provider groups. This presents challenges for rural
      hospitals, which often serve as the foundation for health care delivery in rural
      communities yet struggle to overcome the effects of troubled local economies,
      shortages of health professionals, and public policy inequities. This article
      reviews key trends and challenges facing rural hospitals from the perspective of
      their structure and organization, financial sustainability, quality of care
      provided, and strategic linkages with other entities. It concludes with the
      presentation of a research and policy analysis agenda that addresses the
      feasibility of the role of the rural hospital as the hub or coordinator of the
      rural health care delivery system, the fiscal viability of the rural hospital in
      the post-Balanced Budget Act period, strategies for measuring and improving the
      quality of care provided by rural hospitals, and the structure and value of
      horizontal and vertical linkages of rural hospitals.

PMID- 12061515
TI  - Rural health care providers in the United States.
AB  - One of the most recalcitrant problems of the rural health landscape is the uneven
      distribution and relative shortage of medical care providers. Despite
      considerable efforts by federal and state governments over the past three decades
      to address these problems, rural provider distribution and shortage issues have
      persisted. The purpose of this article is to identify the challenges for rural
      health research and policy regarding health provider supply in the first decade
      of the 21st century. While the emphasis in this article is on physicians,
      workforce concerns pertaining to nurses, nurse practitioners, and physician
      assistants are briefly described. Physician supply, geographic and specialty
      distribution, age, gender, quality of care, recruitment and retention, training,
      productivity and income, reimbursement and managed care, federal and state
      ameliorative programs, safety net, and telehealth are discussed. Also highlighted
      are issues concerning rural health care workforce research, methods, and data as
      well as a series of policy-relevant questions. Solutions to rural health
      personnel problems can only be successfully addressed through multifaceted
      approaches. No vision of the future of rural health can come to fruition if it
      does not promote stable, rewarding, and fulfilling professional and personal
      lives for rural health care providers.

PMID- 12061516
TI  - Developing policies responsive to barriers to health care among rural residents:
      what do we need to know?
AB  - A substantial body of research has been devoted to the subject of access to
      health care services for rural residents, much with the intention of shaping
      government policies to remove barriers or equalize the distribution of health
      care services. A number of programs and policies have grown out of or been
      affected by access research, yet despite identifiable successes of the policy
      research process, barriers to health care services still exist in rural areas.
      This article attempts to stimulate discussion about ways that rural health
      researchers can build on past research on access to care. A framework for posing
      access questions is proposed, suggesting that access research focus on the
      following areas: factors that drive differences in utilization, availability, and
      acceptability; consumer satisfaction and an understanding of why rural consumer
      satisfaction has been found to be high; factors that impede access that are
      mutable; and services that can be shown to improve outcomes.

PMID- 12061517
TI  - Behavioral health: setting the rural health research agenda.
AB  - This article seeks to identify current research priorities in the area of rural
      behavioral health. The method for accomplishing this task begins by identifying
      several domains where policy has a potential to effect improvements in access or
      quality but has been hampered by lack of empirical knowledge. In each domain a
      synthesis of current research summarizes what is known and draws attention to
      knowledge gaps. Research questions in each domain are proposed. The policy
      domains are theoretically based, using a conceptual model of access to health
      care, with a focus on illness level (prevalence), enabling factors (the delivery
      system, organization and financing, the promise of telemedicine), and
      predisposing factors (special populations, beliefs, values, stigma).

PMID- 12061518
TI  - Rural long-term care: what do we need to know to improve policy and programs?
AB  - This article examines what is known and what we need to know about rural long
      term care populations and the formal and informal service systems that support
      their long-term care needs. The article provides a framework for identifying some
      of the critical policy and research questions concerning the financing and
      delivery of rural long-term care that merit the attention of health services
      researchers and policymakers. It documents differences in the demographic and
      health characteristics of the rural and urban elderly and in the availability,
      organization, and use of health and long-term care services in rural areas that
      have significant implications for long-term care policy and programs. With this
      background in mind, the author discusses specific topics and questions relevant
      to long-term care policy and program improvements for rural communities and
      people: (a) the changing role of the rural nursing home; (b) residential care
      alternatives in rural areas; (c) health personnel and rural long-term care; (d)
      the quality of rural long-term care; (e) innovations in long-term care financing
      and service delivery; (f) use of technology in rural long-term care; and (g) the
      effects of Medicaid and Medicare policy changes on the rural long-term care
      system.

PMID- 12061519
TI  - Cartilage-derived biomarkers of osteoarthritis in synovial fluid of dogs with
      naturally acquired rupture of the cranial cruciate ligament.
AB  - OBJECTIVE: To compare synovial fluid biomarkers of cartilage metabolism in joints
      with naturally acquired or experimentally induced cranial cruciate ligament (CCL)
      rupture and determine correlations with stage and severity of disease in dogs.
      ANIMALS: 95 dogs with ruptured CCL, 8 dogs with experimentally ruptured CCL, and
      24 healthy dogs. PROCEDURES: Synovial fluid was assayed for chondroitin sulfate
      neo-epitopes 3B3(-) and 7D4 and glycosaminoglycan (GAG) concentration. Results
      were correlated with demographic data, duration of lameness, radiographic
      osteoarthritis score, and intra-articular lesions. RESULTS: The 7D4
      concentrations and 7D4:GAG in synovial fluid from joints with naturally acquired
      CCL rupture and experimental CCL transection were similar and significantly
      greater than values for healthy control joints. The 3B3(-) concentrations in the
      CCL-deficient groups were not significantly different, although only values in
      the naturally acquired CCL rupture group were significantly greater than those in
      the healthy control group. Within the naturally acquired CCL rupture group there
      was a significant correlation between 3B3(-) and 7D4 concentrations. However,
      there were no significant correlations between biomarker concentrations and
      continuous demographic or disease-related variables or differences in biomarker
      concentrations with different categories of disease. CONCLUSIONS AND CLINICAL
      RELEVANCE: Synovial fluid biomarker concentrations were significantly increased
      in joints with secondary osteoarthritis associated with naturally acquired or
      experimental CCL rupture; however, lack of apparently simple relationships with
      demographic variables or stage or severity of disease limits their clinical
      usefulness.

PMID- 12061520
TI  - Anti-inflammatory effects of carprofen, carprofen enantiomers, and N(G)-nitro-L
      arginine methyl ester in sheep.
AB  - OBJECTIVE: To assess anti-inflammatory effects of carprofen (CPF), CPF
      enantiomers, and N(G)-nitro-L-arginine methyl ester (LNAME) in sheep. ANIMALS: 8
      sheep. PROCEDURE: Sheep with SC tissue cages were used. After intracaveal
      injection of 1% carrageenan, sheep were given single doses of racemic (Rac; 50:50
      mixture of S[+] and R[-] enantiomers)-CPF (4.0 mg/kg), R(-)CPF (2.0 mg/kg),
      S(+)CPF (2.0 mg/kg), LNAME (25 mg/kg), and placebo (PLB) IV in a crossover
      design. RESULTS: Rac-CPF and S(+)CPF inhibited serum thromboxane2 (TXB2) and
      exudate prostaglandin (PG)E2 generation significantly for 32 hours. Maximal
      inhibitory effect for serum TXB2 was 79+/-3% for Rac-CPF and 68+/-6% for S(+)CPF.
      The Rac-CPF and S(+)CPF induced 50 to 98% reversible inhibitory effect for
      exudate PGE2 generation during a 4- to 32-hour period. The R(-)CPF and LNAME
      attenuated serum TXB2 generation significantly. The R(-)CPF did not affect
      exudate PGE2 production, whereas L-NAME potentiated exudate, PGE2 generation by
      30% during 4 to 32 hours. The S(+)CPF and LNAME increased leukotriene B4
      generation and WBC recruitment in exudate although significance was achieved only
      at a few time points. Increase in skin temperature over inflammatory cages was
      effectively inhibited by Rac-CPF and S(+)CPF but not by R(-)CPF CONCLUSIONS AND
      CLINICAL RELEVANCE: Carprofen is a potent cyclooxygenase inhibitor in vivo in
      sheep, and its anti-inflammatory effects are attributable only to S(+)CPF in Rac
      CPF. Nitric oxide may enhance eicosanoid production and accelerate the acute
      inflammatory process.

PMID- 12061521
TI  - Postprandial changes in serum unconjugated bile acid concentrations in healthy
      beagles.
AB  - OBJECTIVE: To investigate postprandial changes in serum concentrations of
      unconjugated bile acids in healthy Beagles. ANIMALS: 7 healthy Beagles.
      PROCEDURE: Blood samples were obtained from dogs at regular intervals up to 8
      hours after consumption of a meal. Serum concentrations of 5 unconjugated bile
      acids were determined at each time point, using gas chromatography-mass
      spectrometry with selected ion monitoring. RESULTS: Total serum unconjugated bile
      acid concentration was significantly increased, relative to baseline values, at
      360, 420, and 480 minutes after feeding. Unconjugated cholic acid was
      significantly increased at 360, 420, and 480 minutes. The proportion of total
      unconjugated bile acids represented by cholic acid was significantly increased at
      240 to 480 minutes. Deoxycholic acid was significantly increased at 360 and 420
      minutes. Chenodeoxycholic acid was significantly increased at 360 to 480 minutes.
      Lithocholic acid was significantly increased at 180 minutes, whereas no
      significant changes in ursodeoxycholic acid were detected at any time point.
      CONCLUSIONS AND CLINICAL RELEVANCE: Healthy Beagles had significant increases in
      serum concentrations and changes in the profile of unconjugated bile acids after
      a meal. These increases persisted > 8 hours, indicating that prolonged
      withholding of food is necessary to avoid the risk of a false-positive diagnosis
      when assessing serum unconjugated bile acid concentrations in dogs.

PMID- 12061522
TI  - Evaluation of leukotriene biosynthetic capacity in lung tissues from horses with
      recurrent airway obstruction.
AB  - OBJECTIVE: To evaluate leukotriene (LT) biosynthetic capacity in lung tissue from
      healthy horses and horses with recurrent airway obstruction (RAO). SAMPLE
      POPULATION: Lung parenchyma and airway specimens from 8 RAO-affected and 5
      healthy horses. PROCEDURE: Horses were stabled for > or = 72 hours. Blood was
      drawn before euthanasia, after which lung specimens were collected. Tissue strips
      from small airways and parenchyma were incubated in organ baths with the
      precursor LTA4 or stimulated with calcium ionophore A23187 or the tripeptide N
      formyl-Met-Leu-Phe (fMLP), with or without exogenous arachidonic acid, in the
      presence of isolated blood neutrophils. RESULTS: Stabling induced typical
      clinical signs of airway obstruction in RAO-affected horses but not control
      horses. When lung parenchyma or airway specimens from both groups of horses were
      incubated with calcium ionophore, with or without arachidonic acid, they did not
      form LT. In contrast, addition of LTA4 to both tissues resulted in conversion to
      LTB4, although concentrations of LTC4 were negligible in airways and parenchymal
      strips from healthy and RAO-affected horses. Incubation of airway and parenchymal
      strips with suspensions of autologous neutrophils did not influence formation of
      LT stimulated by calcium ionophore or fMLP, with or without exogenous arachidonic
      acid. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that lung parenchyma
      and airway tissues themselves are not of substantial importance for LT formation
      in the lungs, although these tissues possessed some LTA4 hydrolase activity,
      enabling LTB4 formation. It may be speculated that LTB4 originates primarily from
      neutrophils and may play a role in the inflammatory events of RAO.

PMID- 12061524
TI  - Evaluation of intestinal intramucosal pH, arterial and portal venous blood gas
      values, and intestinal blood flow during small intestinal ischemia and
      reperfusion in dogs.
AB  - OBJECTIVES: To determine whether small intestinal ischemia and reperfusion
      affects intestinal intramucosal pH (pHi), arterial and portal venous blood gas
      values, and intestinal blood flow (IBF) and to investigate relationships between
      regional intestinal tissue oxygenation and systemic variables in dogs. ANIMALS:
      15 healthy adult Beagles. PROCEDURE: Occlusion of superior mesenteric artery
      (SMA) for 0, 30, or 60 minutes, followed by reperfusion for 180 minutes, was
      performed; IBF, pHi, arterial and portal venous blood gas values, arterial
      pressure, and heart rate were measured at various time points; and intestinal
      mucosal injury was histologically graded. RESULTS: Occlusion of the SMA induced
      significant decreases in pHi and IBF. After the release of the occlusion, IBF
      returned rapidly to baseline values, but improvement in pHi was slow. Arterial
      and portal venous blood gas analyses were less sensitive than tonometric
      measurements of pHi, and there was no correlation between results of blood gas
      analyses and tonometric measurements. Histologic score for intestinal mucosal
      injury increased significantly, depending on duration of ischemia, and there was
      a correlation between tonometric results and the histologic score. CONCLUSIONS
      AND CLINICAL RELEVANCE: Results suggest that it is difficult to accurately
      evaluate local oxygenation disorders by monitoring at the systemic level, whereas
      clinically pHi is the only reliable indicator of inadequate regional intestinal
      tissue oxygenation in dogs.

PMID- 12061523
TI  - Whole-blood concentrations of glutathione in cattle exposed to heat stress or a
      combination of heat stress and endophyte-infected tall fescue toxins in
      controlled environmental conditions.
AB  - OBJECTIVE: To determine whether cattle exposed to heat stress alone or heat
      stress while consuming endophyte-infected fescue (EIF) have lower whole-blood
      (WB) concentrations of glutathione (GSH). ANIMALS: 10 Simmental cows. PROCEDURE:
      Cows were sequentially exposed to thermoneutral (TN; 2 weeks; 18 C, 50% relative
      humidity [RH]), heat stress (HS; 2 weeks; alternating 4-hour intervals at 26 and
      33 C; 50% RH), and heat stress while consuming EIF (10 microg of ergovaline/kg/d;
      2 weeks, HS + EIF). Blood samples were collected after each period and tested for
      GSH and oxidized glutathione (GSSG) concentrations. RESULTS: Feed consumption was
      similar when data were analyzed for time points at which WB concentrations of GSH
      or GSSG were determined. However, significant effects of treatment, cow, days
      exposed to heat, cow-by-treatment interaction, and treatment-by-days exposed to
      heat interaction were detected when data were considered simultaneously. Mean +/-
      SD hematocrit for TN, HS, and HS + EIF were 35.3+/-3, 33.3+/-2, and 37.1+/-3%,
      respectively. Mean WBGSH concentrations for TN, HS, and HS + EIF were 3.2+/-0.65,
      2.7+/-0.62, and 2.4+/-0.56 mmol/L of RBC, respectively. Reduced WBGSH
      concentrations were associated with reduced feed intake during the later part of
      each heat period. CONCLUSIONS AND CLINICAL RELEVANCE: Decreased GSH and increased
      GSSG concentrations were evident during heat stress, especially when cattle
      consumed EIF These were associated with reduced feed intake during heat stress.
      Heat stress, reductions in feed intake, and thermoregulatory effects of EIF may
      induce oxidative stress in cattle.

PMID- 12061525
TI  - Evaluation of lipopolysaccharide-induced activation of equine neutrophils.
AB  - OBJECTIVE: To evaluate lipopolysaccharide (LPS)-induced activation of equine
      neutrophils in blood. SAMPLE POPULATION: Blood samples from 5 healthy adult
      Thoroughbreds. PROCEDURES: Neutrophil integrin (CD11/CD18) expression, size
      variation, degranulation, and deformability were measured with and without
      incubation with LPS. Time and concentration studies were done. The mechanism of
      endotoxin-induced neutrophil activation was investigated by inactivating
      complement or preincubating neutrophils with inhibitors of tumor necrosis factor
      alpha (TNF-alpha) synthesis, prostaglandin-leukotriene synthesis, or platelet
      activating factor. RESULTS: Incubation of equine neutrophils with LPS increased
      cell surface expression of CD11/CD18, decreased neutrophil deformability,
      increased and decreased neutrophil size, and induced neutrophil degranulation.
      The LPS-induced neutrophil activation was attenuated by addition of inhibitors of
      TNF-alpha and prostaglandin-leukotriene synthesis. CONCLUSIONS AND CLINICAL
      RELEVANCE: Equine neutrophils are readily activated in vitro by LPS, resulting in
      increased expression of integrin adhesion molecules, decreased deformability,
      variation in neutrophil size, and degranulation. The tests used to detect
      activated neutrophils in this study may be useful in detecting in vivo neutrophil
      activation in horses with sepsis and endotoxemia.

PMID- 12061526
TI  - Evaluation of the genetic basis of tricuspid valve dysplasia in Labrador
      Retrievers.
AB  - OBJECTIVE: To quantify inheritance of tricuspid valve dysplasia (TVD) in a
      population of Labrador Retrievers and evaluate the possibility of the effect of a
      major locus on TVD. ANIMALS: 521 Labrador Retrievers (345 with known phenotypes
      and 176 related dogs with unknown phenotypes). PROCEDURES: Dogs were considered
      normal, equivocal, and affected for TVD on the basis of echocardiographic
      appearance of the tricuspid valves. Information on related dogs was collected for
      estimation of heritability of the 3 categories of phenotype, using a threshold
      model. Complex segregation analysis was performed to evaluate the possibility of
      the effect of a major locus on TVD. RESULTS: Heritability of TVD in this
      population of dogs was found to be 0.71, a value sufficiently large to suggest a
      segregating major locus. Subsequent complex segregation analysis did not provide
      sufficiently strong evidence to indicate influence of a major locus on the
      prevalence of TVD. However, complex segregation analysis for 2 categories of
      phenotype (eg, equivocal dogs were grouped with affected dogs) suggested that
      there was a single recessive allele with a substantial impact on the expression
      of TVD. CONCLUSIONS AND CLINICAL RELEVANCE: In Labrador Retrievers, TVD is a
      heritable disorder. Affected dogs and dogs closely related to affected dogs
      should not be used for breeding. There was insufficient evidence to suggest the
      influence of a major locus on TVD, although this conclusion was affected by the
      classification of dogs for diagnosis of the condition.

PMID- 12061527
TI  - Assessment of the analgesic effects of ketoprofen in ducks anesthetized with
      isoflurane.
AB  - OBJECTIVE: To determine whether administration of ketoprofen would have analgesic
      effects in spontaneously breathing ducks anesthetized with isoflurane. ANIMALS:
      13 healthy adult wild-strain Mallard ducks. PROCEDURE: Each duck was anesthetized
      twice in a crossover study design with 6 days between randomized treatments.
      Ducks were given ketoprofen (5 mg/kg, IM) or saline (0.9% NaCl) solution after a
      constant plane of anesthesia was established. Analgesia was assessed by measuring
      heart and respiratory rates and duration of application of a noxious stimulus.
      The noxious stimulus was applied 30, 50, and 70 minutes after drug administration
      and was maintained until gross purposeful movements were seen or for a maximum of
      5 seconds. RESULTS: At all 3 evaluation times, heart rate increases in response
      to the noxious stimulus were greater when ducks were given saline solution than
      when they were given ketoprofen. The increase in respiratory rate in response to
      the noxious stimulus was greater when ducks were given saline solution than when
      they were given ketoprofen only 70 minutes after drug administration. When ducks
      were given ketoprofen, duration of the noxious stimulus was significantly longer
      50 and 70 minutes, but not 30 minutes, after drug administration. CONCLUSIONS AND
      CLINICAL RELEVANCE: Ketoprofen reduced the increases in heart and respiratory
      rates associated with application of a noxious stimulus in spontaneously
      breathing adult Mallard ducks anesthetized with isoflurane delivered at
      approximately 2.9%, suggesting that ketoprofen had analgesic effects in these
      ducks. The onset of analgesic effects may be longer than 30 minutes in some
      ducks.

PMID- 12061528
TI  - Effects of selegiline, phenylpropanolamine, or a combination of both on
      physiologic and behavioral variables in healthy dogs.
AB  - OBJECTIVE: To determine effects of selegiline hydrochloride, phenylpropanolamine
      (PPA), or a combination of both on physiologic and behavioral variables in dogs.
      ANIMALS: 40 adult hound-type dogs. PROCEDURE: Dogs were assigned to 4 groups. One
      group received selegiline (1 mg/kg, PO, q 24 h) and PPA (1.1 mg/kg, PO, q 8 h), a
      second group received selegiline alone, a third group received PPA alone, and a
      fourth group received neither drug. Dogs were observed 3 times/d throughout the
      30-day study (daily during the first week, on alternate days during the next 2
      weeks, and again daily during the final week). Observers recorded rectal
      temperature, pulse, respiratory rate, oscillometric blood pressure, and lead-II
      ECG and assessed 4 behaviors, using an analogue scale. Variables were compared
      among treatment groups by use of a 2-factor ANOVA with data categorized into
      three 10-day treatment periods. A similar comparison was made among treatment
      groups with data categorized by time of observation (morning, afternoon, or
      evening) for all study days. RESULTS: Variables did not differ among groups at
      study initiation. Pulse rate was the only variable that differed significantly
      among treatment groups during the study. During the first 10 days of treatment,
      dogs receiving PPA had a lower pulse rate than dogs that did not. Although signs
      of illness were apparent in a few dogs, illness did not appear to be related to
      treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Adverse effects were not detected
      after administration of selegiline, PPA, or a combination of the drugs in healthy
      dogs.

PMID- 12061529
TI  - Effects of the calcium channel antagonist amlodipine in cats with surgically
      induced hypertensive renal insufficiency.
AB  - OBJECTIVE: To determine whether amlodipine besylate decreases systemic arterial
      blood pressure (BP) and reduces the prevalence of complications in cats with
      induced hypertensive renal insufficiency. ANIMALS: 20 cats with partial
      nephrectomy. PROCEDURE: Following reduction in renal mass, 10 cats were
      administered 0.25 mg of amlodipine/kg, PO, q 24 h (group A). Ten cats served as a
      control group (group C). Systolic BP (SBP), diastolic BP (DBP), and mean BP
      (MBP), physical activity, and pulse rate were measured continuously for 36 days
      by use of radiotelemetric devices. RESULTS: Compared with values for clinically
      normal cats, SBP, DBP, and MBP were significantly increased in cats of group C.
      Cats in group A had significant reductions in SBP, DBP, and MBP, compared with
      values for cats in group C. Albuminuria but not urine protein-to-creatinine ratio
      was significantly correlated (R2 = 0.317) with SBP in hypertensive cats.
      Prevalence of ocular lesions attributable to systemic hypertension in group C (7
      cats) was greater than that observed in group A (2). Two cats in group C were
      euthanatized on day 16 because of nuerologic complications attributed to systemic
      hypertension. One normotensive cat in group A was euthanatized because of
      purulent enteritis of unknown cause on day 27. CONCLUSIONS AND CLINICAL
      RELEVANCE: Amlodipine had an antihypertensive effect in cats with coexistent
      systemic hypertension and renal insufficiency. Its use may improve the prognosis
      for cats with systemic hypertension by decreasing the risk of ocular injury or
      neurologic complications induced by high BP.

PMID- 12061530
TI  - Effects of formaldehyde fixation on equine platelets using flow cytometric
      methods to evaluate markers of platelet activation.
AB  - OBJECTIVE: To investigate the effects of formaldehyde fixation on equine
      platelets using flow cytometric methods to evaluate markers of platelet
      activation. SAMPLE POPULATION: Blood samples from 6 Thoroughbreds. PROCEDURE: The
      degree of fluorescence associated with binding of fluorescein isothiocyanate
      (FITC)-conjugated anti-human fibrinogen antibody and FITC-annexin V in
      unactivated and adenosine diphosphate (ADP)-, platelet activating factor (PAF)-,
      and A23187-activated platelet samples in unfixed and 0.5, 1.0, and 2.0%
      formaldehyde-fixed samples was assessed by use of flow cytometry. RESULTS: In
      samples incubated with FITC-anti-human fibrinogen antibody prior to fixation,
      addition of 2.0% formaldehyde resulted in a 30% increase in total fluorescence in
      ADP- and PAF-activated samples and a 60% increase in A23187-activated samples.
      Fixation for 24 hours prior to addition of antibody resulted in reduced
      fluorescence of samples containing antihuman fibrinogen antibody for all 3
      concentrations of formaldehyde in PAF-activated samples. The addition of all 3
      concentrations of formaldehyde after incubation with FITC-annexin V resulted in
      significant increases in fluorescence in unactivated and activated platelet
      samples. As length of fixation time increased, there was a gradual increase in
      fluorescence that was significant at 24 hours. CONCLUSIONS: Because fixation with
      2.0% formaldehyde results in significant changes in fluorescence in activated
      platelet samples containing anti-fibrinogen antibody, lower concentrations of
      formaldehyde should be used to fix equine platelet samples. Formaldehyde-fixed
      platelet samples should be analyzed within 12 hours of fixation to avoid
      artifactual increases in fluorescence. Fixation of samples containing FITC
      annexin V should be avoided because of significant increases in fluorescence that
      may interfere with interpretation of results.

PMID- 12061531
TI  - Kinetics of urinary recovery of five sugars after orogastric administration in
      healthy dogs.
AB  - OBJECTIVE: To describe the kinetics of urinary recovery (UR) of 5 sugars used for
      gastrointestinal permeability and mucosal function testing following orogastric
      administration of lactose, rhamnose, xylose, methylglucose, and sucrose. ANIMALS:
      7 healthy male Beagles. PROCEDURES: A sugar solution containing lactulose,
      rhamnose, xylose, methylglucose, and sucrose was administered by orogastric
      intubation to healthy dogs. Urine samples were collected immediately before sugar
      solution administration (baseline) and at 2-hour intervals thereafter. The UR of
      the 5 sugars was determined from urine concentrations measured by high pressure
      liquid chromatography and pulsed amperometric detection. Percent urinary recovery
      (%UR) of the total UR up to 12 hours after sugar solution administration was
      calculated for each sugar at 2-hour intervals. RESULTS: Mean %UR exceeded 85% for
      all 5 sugars at 6 hours after orogastric administration of the sugar solution and
      exceeded 90% after 8 hours. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy dogs,
      a urine collection period of 6 hours is sufficient for gastrointestinal
      permeability and mucosal function testing following orogastric administration of
      lactulose, rhamnose, xylose, methylglucose, and sucrose.

PMID- 12061532
TI  - Electromyographic changes of motor unit activity in horses with induced
      hypocalcemia and hypomagnesemia.
AB  - OBJECTIVE: To determine whether electromyographic abnormalities are evident in
      skeletal muscles in horses with induced hypocalcemia and hypomagnesemia. ANIMALS:
      7 healthy adult Dutch Warmblood horses. PROCEDURES: Electromyographic examination
      was performed in the lateral vastus, triceps, and subclavian muscles before and
      after IV infusion of EDTA. An initial dose (mean +/- SD, 564+/-48 ml) of a 10%
      solution of sodium EDTA was administered IV during a period of 21+/-73 minutes to
      establish a blood concentration of ionized calcium of approximately 0.5 mmol/L.
      Average rate of EDTA infusion to maintain ionized calcium at this concentration
      was 6.6 ml/min. RESULTS: Mean blood concentrations of ionized calcium and
      magnesium were 1.39+/-0.06 and 0.84+/-0.09 mM, respectively before EDTA infusion;
      after EDTA infusion, concentrations were 0.48+/-0.05 and 0.44+/-0.20 mM,
      respectively. This state induced positive waves; fibrillation potentials;
      doublets, triplets, and multiplets; complex repetitive discharges; and
      neuromyotonia. Analysis of motor unit action potentials (MUAP) after EDTA
      infusion revealed an increase in prevalence of polyphasic and complex MUAP in all
      muscles. CONCLUSIONS AND CLINICAL RELEVANCE: None of the horses had classical
      signs of hypocalcemia and hypomagnesemia. In contrast, all horses had spontaneous
      activity in the measured muscles indicative of nerve hyperirritability. Calcium
      and magnesium deficits appear to have consequences, which may be subclinical,
      affecting functions of the neuromuscular system. This is of interest for
      equestrian sports in which hypocalcemia and hypomagnesemia are expected, such as
      during endurance rides.

PMID- 12061533
TI  - Effects of an abrupt increase of starch-rich concentrates in the diet of dairy
      cows on concentrations of volatile fatty acids in the rumen and large intestine
      and on myoelectric activity of the spiral colon.
AB  - OBJECTIVES: To describe the effects of an abrupt increase of concentrates in the
      diet of dairy cows on myoelectric activity of the spiral colon and on
      fermentation patterns in the rumen and large intestine. ANIMALS: 6 healthy
      lactating Simmental x Red-Holstein cows. PROCEDURES: The diet of 6 cows implanted
      with bipolar electrodes in the spiral colon was changed from hay only to a ration
      of 50% hay:50% starch-rich concentrates during a period of 60 hours. Myoelectric
      activity of the spiral colon, concentrations of absolute and undissociated
      volatile fatty acids (VFA), and pH of ruminal and large intestinal contents were
      monitored before, during, and after the dietary change. RESULTS: Significant
      changes in patterns of myoelectric activity of the spiral colon were restricted
      to phases III and IV of the bovine migrating myoelectric complex and to
      propagation velocity. Significant alterations were not observed in pH or VFA
      concentrations in ruminal fluid, but pH decreased and VFA concentrations
      increased significantly in fecal specimens after the change of diet. CONCLUSIONS
      AND CLINICAL RELEVANCE: Although rumen fluid is of limited value for measurement
      of certain indicators of fermentation, fecal samples can be used for measurement
      of pH and VFA concentrations, which serve as indicators of fermentation patterns
      in the large intestine. Increased concentrations of VFA and low pH in large
      intestinal digesta have a minimal influence on myoelectric activity of the spiral
      colon. Increased luminal VFA concentrations are unlikely to play an important
      role in the etiopathogenesis of motility disorders of the large intestine in
      cattle.

PMID- 12061534
TI  - Comparison of pharmacokinetic variables for two low-molecular-weight heparins
      after subcutaneous administration of a single dose to horses.
AB  - OBJECTIVE: To determine pharmacokinetic variables and to evaluate the influence
      on clotting times after SC administration of single doses of dalteparin and
      enoxaparin to horses. ANIMALS: 5 healthy adult horses. PROCEDURES: The study was
      designed as a 4-period crossover study. Each horse received a single SC injection
      of dalteparin (50 and 100 anti-Xa U/kg) and enoxaparin (40 and 80 anti-Xa U/kg).
      Plasma anti-Xa activities and clotting times were measured, and pharmacokinetic
      variables were determined. Absolute and relative maximal prolongation of clotting
      times was calculated, and correlation between plasma anti-Xa activities and
      clotting times was determined. RESULTS: The SC administration of each of the
      doses of the 2 preparations was well tolerated. Time course of the anti-Xa
      activities could be described in a 1-compartment model. Comparison of low- and
      high-dose treatments revealed a disproportionate increase of the area under the
      plasma activity-time curve and prolongation of the terminal half-life, but the
      increase in maximum plasma activity was proportionate, and peak plasma
      concentrations corresponded with concentrations recommended in human medicine.
      There were only mild changes in activated partial thromboplastin time (aPTT),
      whereas the influence on thrombin time (TT) was greater, dose-dependent, and more
      variable. A weak-to-moderate correlation between aPTT and plasma anti-Xa
      activities and a moderate-to-strong correlation between TT and plasma anti-Xa
      activities were found. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic and
      anticoagulatory properties of low-molecular-weight heparins in horses are similar
      to those found in humans. Once-daily SC administration of dalteparin or
      enoxaparin may be useful as an anticoagulatory treatment in horses.

PMID- 12061535
TI  - Evaluation of cross-reactivity of allergens by use of intradermal testing in
      atopic dogs.
AB  - OBJECTIVE: To examine cross-reactivity of aeroallergens in Colorado and
      surrounding states by evaluating concurrent positive reactions of related and
      nonrelated allergens of intradermal tests in dogs. SAMPLE POPULATION: Intradermal
      test results of 268 atopic dogs. PROCEDURE: A retrospective evaluation of skin
      test results for 268 dogs was performed. Pairs of closely related and nonrelated
      allergens were evaluated. Group 1 consisted of closely related allergens with
      demonstrated antibody cross-reactivity in humans. In group 2, allergens of the
      same plant group (ie, trees, grasses, or weeds) that were not closely related
      were paired. In group 3, allergen pairs were of different plant groups. Plant
      allergens were paired with dust mite allergens, animal dander, or mold spores in
      group 4. In the last group, allergens not derived from plants were paired. Data
      were evaluated twice by use of a different definition of a positive reaction.
      Significance of the difference between group means of log odds ratios was
      estimated by use of a boot-strap percentile confidence interval. RESULTS:
      Significant differences in the number of concurrent positive reactions were not
      found between related versus nonrelated grass, weed, or tree allergens.
      Significant differences in the number of concurrent positive reactions were found
      between plant allergens of different groups (ie, grasses, weeds, and trees) and
      plant allergens of the same groups, related or nonrelated, as well as between
      plant-derived and nonplant-derived allergens. Many dogs reacting to a specific
      allergen did not react to a closely related allergen at the same time.
      CONCLUSION: These results provide evidence against clinically relevant cross
      reactivity and suggest that allergen-specific immunotherapy should be formulated
      on the basis of single allergen test results.

PMID- 12061536
TI  - Effect of seminal plasma concentration and various extenders on postthaw motility
      and glass wool-Sephadex filtration of cryopreserved stallion semen.
AB  - OBJECTIVE: To compare the effect of semen extender and seminal plasma on postthaw
      motility and filtration through a glass wool-Sephadex (GWS) filter for frozen
      stallion semen. SAMPLE POPULATION: 7 stallions from which we collected > or = 3
      ejaculates/stallion. PROCEDURES: 4 experiments were conducted to evaluate
      postthaw quality of frozen stallion semen. Kenney extender was compared with
      glucose-EDTA extender by use of various dilution rates that resulted in differing
      concentrations of seminal plasma. Stallions known to produce semen with poor
      postthaw quality were used to investigate whether a particular extender or
      dilution rate could improve ability of such semen to survive freeze-thaw
      procedures. RESULTS: Use of Kenney extender as the centrifugation extender
      significantly improved postthaw motility and GWS filtration, compared with
      glucose-EDTA. Extending semen at a dilution of 1:3 was significantly better than
      1:1 for both motility and GWS filtration. In addition, including seminal plasma
      at a concentration of 5% in the cryopreserved semen resulted in significantly
      higher yield of spermatozoa after GWS filtration, compared with complete removal
      of SP or use of seminal plasma at 25%. Lastly, semen with poor postthaw quality
      had significantly improved postthaw quality in regard to motility and GWS
      filtration when semen was frozen with seminal plasma at a concentration of 5%,
      compared with semen frozen with seminal plasma at a concentration of 25%.
      CONCLUSIONS AND CLINICAL RELEVANCE: Use of Kenney extender at a high dilution (>
      or = 1:3) immediately after collection of semen can improve postthaw quality of
      frozen stallion semen.

PMID- 12061537
TI  - Characterization of lipoproteins in cerebrospinal fluid of mares during pregnancy
      and lactation.
AB  - OBJECTIVE: To measure apolipoproteins in cerebrospinal fluid (CSF) from healthy
      mares and to determine whether CSF concentrations of apolipoproteins change
      during pregnancy and lactation. ANIMALS: 5 healthy pregnant mares. PROCEDURE: 2
      sets of CSF samples were obtained; initial samples were obtained 10 to 30 days
      before parturition (mean, 18 days; median, 17 days), and second samples were
      obtained 19 to 26 days after parturition (mean, 23 days; median, 23 days).
      Cerebrospinal fluid was collected from the lumbosacral subarachnoid space of
      standing horses by use of routine collection techniques. Cerebrospinal fluid
      cholesterol concentrations were measured by use of a sensitive enzymatic assay.
      Ultracentrifugal fractions of CSF lipoproteins were characterized by determining
      the distribution of apolipoproteins, using polyacrylamide gel electrophoresis.
      RESULTS: Analyses of isolated ultracentrifugal fractions by polyacrylamide gel
      electrophoresis revealed 2 apolipoproteins, with the expected molecular weights
      for apolipoprotein E and apolipoprotein A-I. No significant differences were
      observed between pre- and postpartum values in mares. The concentration of
      cholesterol in CSF fluid of mares was comparable to values reported in other
      mammals. CONCLUSIONS AND CLINICAL RELEVANCE: Apolipoprotein E in CSF of horses is
      a major apolipoprotein associated with high-density lipoproteins, which is
      similar to findings in other mammals. Additional characterization of the role of
      apolipoproteins in mammalian CSF may provide critical insight into various
      degenerative neurologic disease processes.

PMID- 12061538
TI  - Assessment of plasma carnitine concentrations in relation to ceroid
      lipofuscinosis in Tibetan Terriers.
AB  - OBJECTIVE: To determine whether the late onset form of inherited ceroid
      lipofuscinosis (CL) in Tibetan Terriers is accompanied by low plasma carnitine
      concentrations prior to the appearance of clinical signs. ANIMALS: 129 healthy
      Tibetan Terriers, 12 Tibetan Terriers with CL, and 95 healthy purebred dogs of
      other breeds. PROCEDURE: After withholding food, blood samples were collected
      from all dogs into tubes containing EDTA. Blood samples were analyzed for plasma
      free carnitine and acyl-carnitines concentrations. RESULTS: Neither the mean
      plasma total carnitine concentration nor the mean fraction of carnitine in the
      free form differed significantly between Tibetan Terriers with CL and healthy
      Tibetan Terriers. Among Tibetan Terriers and the general dog population, plasma
      carnitine concentration increased with age. Castrated males had an overall
      increase in plasma carnitine concentrations and variability, compared with
      sexually intact males. By comparison, plasma carnitine concentrations were not
      significantly different between spayed and sexually intact females. The mean
      plasma carnitine concentration in the Tibetan Terriers was approximately 22%
      higher than in the general population of healthy dogs of other breeds.
      CONCLUSIONS AND CLINICAL RELEVANCE: Contrary to what is seen in early onset CL in
      English Setters and in humans with some forms of CL, plasma carnitine
      concentrations are not decreased in the late-onset disorder in Tibetan Terriers.
      Our large-scale study establishes reference range values for plasma carnitine
      concentrations in dogs as functions of age and sex that will be useful in
      evaluating potential carnitine deficiencies in other disorders in dogs.

PMID- 12061539
TI  - Fatigue microdamage in the radial predilection site for osteosarcoma in dogs.
AB  - OBJECTIVE: To evaluate whether body size and anatomic site influence the quantity
      of bone microdamage in dogs without osteosarcoma (OS). SAMPLE POPULATION: Pairs
      of radii were collected from 10 small dogs (< 15 kg) and 10 large dogs (> 25 kg).
      PROCEDURE: Specimens were stained in basic fuchsin for bone microdamage.
      Transverse sections were cut from each proximal and distal radial metaphysis at
      15 and 85% of bone length. The following variables were determined for each
      region: mean microcrack length (CrLe, microM), microcrack density (CrDn,
      microcracks/mm2), microcrack surface density (CrSDn, microm/mm2), and estimated
      activation frequency (Acf, microcracks/mm2/y). RESULTS: Metaphyseal region did
      not significantly influence CrDn, CrLe, and CrSDn. The CrDn and CrSDn were
      influenced by body size, with microdamage being increased in large dogs, compared
      with small dogs. However, mean CrLe was not significantly influenced by body
      size. Acf significantly decreased with age and was significantly decreased in
      large dogs and in the distal radial metaphysis, compared with small dogs and the
      proximal radial metaphysis, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Our
      data did not reveal an increase in microdamage or remodeling at the OS
      predilection site (ie, the distal metaphysis of the radius), suggesting that
      induction of microdamage and an associated increase in bone remodeling are
      unlikely to be an important risk factor for induction of OS.

PMID- 12061540
TI  - In vitro characterization of the inhibitory effects of ketoconazole on metabolic
      activities of cytochrome P-450 in canine hepatic microsomes.
AB  - OBJECTIVE: To evaluate the inhibitory potency of ketoconazole (KTZ) on the
      metabolic activities of isozymes of cytochrome P-450 (CYP) in dogs. ANIMALS: 4
      healthy 1-year-old male Beagles. PROCEDURE: Hepatic microsomes were harvested
      from 4 dogs after euthanasia. To investigate the effects of KTZ on CYP metabolic
      activities, 7-ethoxyresorufin, tolbutamide, bufuralol, and midazolam
      hydrochloride were used as specific substrates for CYP1A1/2, CYP2C21, CYP2D15,
      and CYP3A12, respectively. The concentrations of metabolites formed by CYP were
      measured by high-performance liquid chromatography, except for the resorufin
      concentrations that were measured by a fluorometric method. The reaction velocity
      substrate concentration data were analyzed to obtain kinetic variables, including
      maximum reaction velocity, Michaelis-Menten constant, and inhibitory constant
      (Ki). RESULTS: KTZ competitively inhibited 7-ethoxyresorufin O-deethylation and
      midazolam 4-hydroxylation; it noncompetitively inhibited tolbutamide
      methylhydroxylation. Bufuralol 1'-hydroxylation was inhibited slightly by KTZ.
      The mean Ki values of KTZ were 10.6+/-6.0, 170+/-2.5, and 0.180+/-0.131 microM
      for 7-ethoxyresorufin O-deethylation, tolbutamide methylhydroxylation, and
      midazolam 4-hydroxylation, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: In
      dogs, KTZ at a therapeutic dose may change the pharmacokinetics of CYP3A12
      substrates as a result of inhibition of their biotransformation. Furthermore, no
      influence of KTZ on the pharmacokinetics of CYP1A1/2, CYP2C21, and CYP2D15
      substrates are likely. In clinical practice, adverse drug effects may develop
      when KTZ is administered concomitantly with a drug that is primarily metabolized
      by CYP3A12.

PMID- 12061541
TI  - Effects of cyclophotocoagulation with a neodymium:yttrium-aluminum-garnet laser
      on corneal sensitivity, intraocular pressure, aqueous tear production, and
      corneal nerve morphology in eyes of dogs.
AB  - OBJECTIVE: To determine effects of cyclophotocoagulation via administration of
      100 J with a neodymium:yttrium aluminum garnet (Nd:YAG) laser on corneal touch
      threshold (CTT), intraocular pressure (IOP), aqueous tear production, and corneal
      nerve morphology in eyes of dogs. ANIMALS: 15 dogs. PROCEDURE: Noncontact Nd:YAG
      laser was transsclerally applied (10 applications; 25 W for 0.1 seconds for each
      application to each of 4 quadrants) to the ciliary body of the left eye of 15
      dogs; the right eye was the control eye. Corneal integrity, CTT, tear production
      as measured by the Schirmer tear test (STT), and IOP were evaluated for 14 days
      following laser treatment. On day 14, dogs were euthanatized, eyes harvested, and
      corneas stained with gold chloride. Major nerve bundles were analyzed by use of a
      drawing tube attached to a light microscope, and maximum diameters were measured
      by use of image analysis software. RESULTS: All laser-treated eyes had
      significantly higher CTT values, compared with control eyes. Six of 15 laser
      treated eyes developed ulcerative keratitis. On most days, IOP was significantly
      lower in laser-treated eyes in both morning and evening. Laser-treated eyes had a
      significant decrease of approximately 1 nerve bundle/corneal quadrant. Values for
      STT or nerve bundle diameters did not differ significantly. CONCLUSIONS AND
      CLINICAL RELEVANCE: Administration of 100 J with a Nd:YAG laser effectively
      reduced IOP while increasing CTT and caused a significant decrease in number, but
      not diameter, of major corneal nerve bundles. Nerve damage and corneal
      hypoesthesia are etiologic factors in ulcerative keratitis following Nd:YAG
      cyclophotocoagulation.

PMID- 12061542
TI  - Indocarbazostatin and indocarbazostatin B, novel inhibitors of NGF-induced
      neuronal differentiation in PC12 cells. I. Screening, taxonomy, fermentation and
      biological activities.
AB  - During the course of our screening for modulators of signal transduction of
      mammalian cells, we discovered two novel indolocarbazole antibiotics,
      indocarbazostatin and indocabazostatin B, from a culture broth of a Streptomyces
      sp. as inhibitors of NGF-induced neuronal differentiation in rat pheochromocytoma
      PC12 cells. Indocarbazostatin and indocarbazostatin B inhibited NGF-induced
      neurite outgrowth from PC12 cells at 6 nM and 24 nM, respectively, whereas K-252a
      inhibited at 200 nM under our assay conditions.

PMID- 12061543
TI  - Indocarbazostatin and indocarbazostatin B, novel inhibitors of NGF-induced
      Neuronal differentiation in PC12 cells. II. Isolation, physicochemical properties
      and structural elucidation.
AB  - Two novel indolocarbazol-type bioactive molecules, indocarbazostatin (1) and
      indocarbazostatin B (2), were isolated as inhibitors of NGF-induced neuronal
      differentiation in rat pheochromocytoma PC12 cells from a culture broth of a
      Streptomyces sp. The structures of these compounds were determined by HR-FAB-MS,
      UV, 1H and 13C NMR, 1H-1H COSY, PFG HMBC, PFG HMQC and DIF NOE experiments. The
      relative and absolute configurations were deduced from MM2, MOPAC and CONFLEX
      calculations, and CD analyses. The imide/amide sector rule was proposed from the
      analyses of CD data of 1 and other indolocarbazole antibiotics. It was concluded
      that the minor compound 2 has a negative atropisomeric chirality in the aglycone.

PMID- 12061544
TI  - Anicequol, a novel inhibitor for anchorage-independent growth of tumor cells from
      Penicillium aurantiogriseum Dierckx TP-F0213.
AB  - A novel inhibitor for anchorage-independent growth of tumor cells was isolated
      from the culture broth of a fungal strain. The producing strain TP-F0213 was
      identified as Penicillium aurantiogriseum Dierckx based on the taxonomic study.
      The compound designated anicequol was obtained by solvent extraction, HP-20 and
      silica gel chromatographies and recrystallization. The planar structure was
      elucidated by NMR analysis to be 16-acetoxy-3,7,11-trihydroxyergost-22-en-6-one.
      The absolute configuration was determined by the X-ray analysis of 3,7-bis-p
      bromobenzoyl derivative. The carbon skeleton of anicequol has the same absolute
      configuration as ergostane and the configurations of substituents are 3beta,
      5alpha, 7beta, 11beta, 16beta and 24S. Anicequol inhibited the anchorage
      independent growth of human colon cancer DLD-1 cells with the IC50 of 1.2 microM
      whereas the IC50 against anchorage-dependent growth was 40 microM.

PMID- 12061545
TI  - Neosordarin and hydroxysordarin, two new antifungal agents from Sordaria
      araneosa.
AB  - Two novel antifungal agents belonging to the sordarin family have been isolated
      from fermentations of Sordaria araneosa by bioassay-guided purification and their
      structures elucidated by NMR techniques. Neosordarin (1) is closely related to
      the recently discovered hypoxysordarin (2), with only small differences on the
      aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose
      moiety. Hydroxysordarin (3) closely resembles sordarin (4), the only slight
      difference being the replacement of sordarose with altrose as the sugar unit.

PMID- 12061546
TI  - Radamycin, a novel thiopeptide produced by streptomyces sp. RSP9. I. Taxonomy,
      fermentation, isolation and biological activities.
AB  - The newly isolated strain Streptomyces sp. RSP9 produces two thiopeptides; one of
      them is methylsulfomycin I, which shows potent antibiotic activity against
      several gram-positive bacteria such as Micrococcus luteus and Staphylococcus
      aureus. The other is a new thiopeptide named radamycin. In the present work, this
      compound was purified and tested against several microorganisms and no antibiotic
      activity was detected in the assays. However, it does have a very strong capacity
      as an inducer of the tipA promoter, and indeed is the first reported molecule
      with tipA promoter induction capacity without detectable antibiotic activity.
      Induction of the tipA promoter also occurs with methylsulfomycin I.

PMID- 12061547
TI  - Radamycin, a novel thiopeptide produced by streptomyces sp. RSP9. II. Physico
      chemical properties and structure determination.
AB  - The new cyclic peptide antibiotic, radamycin (1) and the known thiopeptide
      methylsulfomycin I (2) have been isolated from the fermentation broth of a
      Streptomyces sp. RSP9. The structure of radamycin was elucidated by NMR, LC-MS
      and FAB-MS and was established as a thiopeptide with oxazole and thiazole
      moieties, and several unusual amino acids.

PMID- 12061548
TI  - New insights into rifamycin B biosynthesis: isolation of proansamycin B and 34a
      deoxy-rifamycin W as early macrocyclic intermediates indicating two separated
      biosynthetic pathways.
AB  - Proansamycin B, the formerly postulated intermediate of rifamycin B biosynthesis,
      was isolated from cultures of the Amycolatopsis mediterranei mutant F1/24. The
      structure was determined using UV, IR, NMR and MS techniques. Biotransformation
      studies demonstrate that proansamycin B is an intermediate of a shunt pathway, a
      8-deoxy variant, of rifamycin B biosynthesis leading to 8-deoxy-rifamycin B as
      the final product. In addition, 34a-deoxy-rifamycin W, the direct precursor of
      rifamycin W, could be isolated representing the earliest macrocyclic intermediate
      obtained so far in the biosynthetic route to rifamycin B. Furthermore, the new
      rifamycin W-28-desmethyl-28-carboxy and rifamycin W-hemiacetal, intermediates in
      the transformation sequence of rifamycin W to rifamycin S, were isolated.
      Application of proton NMR measurements (double resonance and ROESY experiments)
      on the latter compound indicated that the stereochemistry at the chiral center C
      28 is R.

PMID- 12061549
TI  - Identifying protein kinase inhibitors using an assay based on inhibition of
      aerial hyphae formation in Streptomyces.
AB  - We have identified a strain of Streptomyces in which aerial hyphae formation
      appears to be especially sensitive to inhibition by protein kinase inhibitors.
      Using this assay, a number of bacterial cultures have been screened and novel
      inhibitors of eukaryotic protein kinases have been identified. Since M.
      tuberculosis possesses multiple eukaryotic-like protein kinase genes, we tested
      the active kinase inhibitors for the inhibition of mycobacterial growth and
      obtained several potent compounds. This identifies a new biochemical class of
      antimycobacterial agents.

PMID- 12061551
TI  - Confirmation of the antibacterial mode of action of SB-219383, a novel tyrosyl
      tRNA synthetase inhibitor from a Micromonospora sp.
AB  - The compound designated SB-219383 is a potent and selective inhibitor of
      bacterial tyrosyl tRNA synthetases. It exhibits an IC50 of < 1 nM against
      Staphylococcus aureus tyrosyl tRNA synthetase and weak in vitro activity against
      Staphylococci and Streptococci. Here we present data consistent with SB-219383
      eliciting an amino acid starvation in both S. aureus and Streptococcus
      pneumoniae, supporting the conclusion that the antibacterial activity of SB
      219383 is due to tyrosyl tRNA synthetase inhibition.

PMID- 12061550
TI  - PPARgamma activation and adipocyte differentiation induced by AS-6, a prenyl
      phenol antidiabetic antibiotic.
AB  - The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce
      serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I
      and II diabetes. However, little is known about the molecular mechanism for these
      physiological effects. Here we report that the ascochlorin derivative, 4-O
      carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear
      hormone receptor, PPARgamma, although it does not activate the related receptors,
      PPARalpha, PPARdelta or RARalpha. AS-6 interacts directly with the PPARgamma
      molecule in vitro, and induces differentiation of the mouse preadipocyte cell
      line 3T3-L1. Our results suggest that AS-6 is a partial agonist for PPARgamma
      with a novel chemical structure.

PMID- 12061552
TI  - Synthesis and in vitro antimicrobial activity of 3-keto 16-membered macrolides
      derived from tylosin.
AB  - Several series of 14-membered ketolides derived from erythromycin exhibit useful
      antimicrobial activity against macrolide-resistant bacteria. To determine if 16
      membered ketolides may possess analogous activity, 3-keto derivatives of 5-O
      mycaminosyl-23-O-acetyltylonolide and desmycosin were synthesized by protection
      of susceptible functional groups, oxidation of the 3-hydroxyl group under
      modified Moffatt-Pfitzner conditions, and subsequent deprotection. The resulting
      3-keto products unexpectedly adopted the 2,3-trans enol rather than the 3-keto
      tautomer. The trans configuration of the 2,3-double bond in the macrolide chain
      is most likely the result of hydrogen bond stabilization between the enol
      hydroxyl and lactone carbonyl, which places these two groups in a cis
      relationship. This preference for the enol tautomer in 16-membered macrolides is
      not seen with 14-membered ketolides. The in vitro antimicrobial activity of the
      enol derivatives was greatly reduced compared to their unoxidized parent
      compounds, but the reduced antimicrobial activity of the enol derivatives
      paralleled results from corresponding 2,3-anhydro derivatives of 16-membered
      macrolides, which also have 2,3-trans stereochemistry. These results are in
      contrast to those from 14-membered-ring macrolides in which 3-keto and 2,3
      anhydro derivatives exhibit greater activity than 3-hydroxy compounds.

PMID- 12061553
TI  - Microbial hydroxylation of zofimarin, a sordarin-related antibiotic.

PMID- 12061554
TI  - Absolute configuration of migrastatin, a novel 14-membered ring macrolide.

PMID- 12061555
TI  - Ethylenediamine as eluent component in cation chromatography. Predictive and
      comparative study for analysis of alkaline earth ions.
AB  - The retention behaviour of alkaline earth cations was studied as a function of
      changing composition of acidified ethylenediamine eluent. The multiple eluent
      species retention model developed for separation of calcium, magnesium and
      strontium ions was utilized for determination of selectivity coefficients for
      sample and eluent ions. The suggested model accurately describes and predicts
      retention of analytes under elution conditions [0.5-2.0 mM C2H4(NH2)2 and pH 4-6]
      which are of practical importance. The results in three-dimensional retention
      surface with species distribution graphs are demonstrated. Complexometric
      titrations and ion chromatography (IC) were compared for the analysis of calcium
      and magnesium ions. Statistical data indicated that there was no evidence for
      relative differences between the two methods. However, IC gives several
      advantages over volumetric method.

PMID- 12061556
TI  - Gas chromatographic determination of vapour pressure and related thermodynamic
      properties of monoterpenes and biogenically related compounds.
AB  - The (subcooled) liquid vapour pressure, heat of vapourization and gas-liquid heat
      capacity difference of monoterpenes and biogenically related compounds were
      determined by a gas-liquid chromatographic method based on Kovats retention
      indices. Compared to those used in previous studies using the same method, these
      compounds are structurally diverse and have relatively low boiling points.
      Despite of this and even though the difference in activity coefficients in the
      chromatographic column stationary phase between the test and reference compounds
      were ignored, results for vapour pressure compare favorably with experimental
      literature data. The results indicate that the method can be improved by
      introducing temperature dependent activity coefficients, preferably based on a
      physicochemical model for gas-liquid partitioning.

PMID- 12061557
TI  - Gas chromatographic determination of glutaraldehyde in the workplace atmosphere
      after derivatization with 0-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine on a solid
      phase microextraction fibre.
AB  - Glutaraldehyde is used primarily in hospital environments for the disinfection of
      various instruments (e.g., endoscopes). We describe in this paper the measurement
      of glutaraldehyde in a hospital environment using solid-phase microextraction.
      The method includes, prior to sampling, the adsorption of O-(2,3,4,5,6
      pentafluorobenzyl)hydroxylamine on to the fibre (with polydimethylsiloxane
      divinylbenzene). The fibre is then exposed to air, after which desorption is
      performed in the GC injection port. This process results in the formation of a
      stable derivative of the glutaraldehyde that is suitable for chromatographic
      purposes and detectable with classical detection methods, such as flame
      ionisation and electron-capture detection. We demonstrate that the procedure of
      adsorption, thermal desorption and derivatization is robust and reproducible. We
      were able to detect concentrations of 60 microg/m3 (10 s sampling) or 6 microg/m3
      (120 s sampling) by electron-capture detection, and 80 microg/m3 (120 s sampling)
      by flame ionisation detection. We compared our method to currently existing
      methods of glutaraldehyde measurement and highlighted several important
      advantages of the method.

PMID- 12061558
TI  - New triazine spectroscopic reagent for the separation of DL-amino acids by
      micellar electrokinetic chromatography.
AB  - An approach to the chiral separation of racemic mixtures of amino acids by means
      of micellar electrokinetic chromatography after derivatization with a new
      triazine spectroscopic reagent, 3-(4,6-dichloro-1,3,5-triazinylamino)-7
      dimethylamino-2-methylphenazine (DTDP), has been evaluated. It was found that the
      derivatives of the aliphatic amino acids such as serine, valine and arginine,
      could produce a strong UV absorption at 282 nm, whose apparent molar
      absorptivities are of 10(-4) M(-1) cm(-1), and thus the concentration of the
      amino acids down to 3 x 10(-7) M can still give a detectable signal (S/N = 3).
      Beta-Cyclodextrin (beta-CD) added to the buffer system was used as a chiral
      selector, and separation conditions were optimized. The presence of an organic
      modifier (2-propanol) was also a prerequisite for the chiral separation. The best
      results for the chiral separation of DTDP-amino acids were achieved in a mixed
      sodium dodecylsulfate-beta-CD-borate-2-propanol medium at pH 9.0. Compared to
      some of the commonly used derivatization methods, the present one offers a
      relatively stable derivative and strong UV absorption for the spectroscopically
      inert amino acids, thus enabling amino acids to be separated and detected by CE
      even with a simpler UV detector.

PMID- 12061559
TI  - Chiral separation of amino acids derivatized with fluoresceine-5isothiocyanate by
      capillary electrophoresis and laser-induced fluorescence detection using mixed
      selectors of beta-cyclodextrin and sodium taurocholate.
AB  - Chiral separation of 20 pairs of amino acids derivatized with fluoresceine-5
      isothiocyanate (FITC) by capillary electrophoresis and laser-induced fluorescence
      detection was studied using the mixture of beta-cyclodextrin (beta-CD) and sodium
      taurocholate (STC) as selector. Resolution was considerably superior to that
      obtained by using either beta-CD or STC alone. The molar ratio of beta-CD to STC
      of about 2:3 was found to be critical to achieve maximum separation. At this beta
      CD-to-STC ratio, chiral separation occurred at really low total concentration of
      beta-CD and STC (<0.1 mM). Other impacting factors were investigated including
      the total concentration of beta-CD and STC, pH, and capillary conditioning
      procedure between two successive runs. Using a running buffer of 80 mM borate
      containing 20 mM beta-CD and 30 mM STC at pH 9.3, all of the 20 pairs of FITC
      amino acid enantiomers were baseline resolved. The resolutions of the most pairs
      of the amino acid enantiomers (17 of 20) were higher than 3.0, only three pairs
      gave a resolution lower than 3.0 but higher than 1.90 (beta-phenylserine, pSer).
      The highest resolution reached 14.58 (Glu). Two derivatives of beta-CD, 2
      hydroxypropyl-beta-CD (HP-beta-CD) and heptakis(2,6-di-O-methyl)-beta-CD (DM-beta
      CD) were also explored. HP-beta-CD showed similar cooperative effect with STC,
      while DM-beta-CD together with STC led to poorer chiral separation.

PMID- 12061561
TI  - Prediction of the retention in reversed-phase liquid chromatography using solute
      mobile phase-stationary phase polarity parameters.
AB  - A previously reported algorithm, based on the equation: log k = (log k)o +
      p(PN(m) - PN(s)), that relates the retention in reversed-phase liquid
      chromatography with solute (p), mobile phase (PN(m)) and stationary phase (PN(s))
      relative polarity parameters, is improved. The retention data reported by several
      authors for different sets of compounds, eluted with acetonitrile-water and
      methanol-water mixtures, are used to test the algorithm and elaborate a database
      of p values. The methodology is successfully applied to predict the retention
      using PN(m), values calculated as PN(m) = 1.00 - (2.13phi)/(1+1.4phi) for
      acetonitrile-water and PN(m) = 1.00 - (1.33phi)/(l1 + 0.47phi) for methanol
      water, phi being the organic solvent volumetric fraction. The polarity parameters
      are demonstrated to be useful to transfer retention data between solvent systems
      and between columns. Accordingly, the retention in a solvent system is predicted
      by characterising the working column with a small training set of compounds
      having diverse polarities, and using the p values known for another solvent
      system or column. The p polarity parameter is found to be a good descriptor of
      the retention, allowing the prediction of the expected elution order and peak
      overlaps.

PMID- 12061560
TI  - Direct high-performance liquid chromatographic enantioseparation of apolar beta
      amino acids on a quinine-derived chiral anion-exchanger stationary phase.
AB  - A quinine-derived chiral anion-exchanger stationary phase was applied for the
      direct high-performance liquid chromatographic separation of the enantiomers of N
      protected unusual beta-amino acids, i.e. 3-aminobutanoic acid, 3-aminopentanoic
      acid, 3-amino-4-methylpentanoic acid, 3-amino-4,4-dimethylpentanoic acid, 3-amino
      4-methylhexanoic acid, 3-amino-4-ethylhexanoic acid, 3-amino-3
      cyclohexylpropanoic acid, 3-amino-3-(3-cyclohexen-1-yl)propanoic acid and 3-amino
      3-phenylpropanoic acid. The readily prepared N-2,4-dinitrophenyl derivatives were
      well separable, with good efficiency and high resolution. The chromatographic
      conditions (eluent composition, pH and buffer concentration) were varied to
      achieve optimal separation. In some cases, the elution sequences of the
      enantiomers of the derivatives were determined.

PMID- 12061562
TI  - Measurement and modeling of the equilibrium behavior of the Troger's base
      enantiomers on an amylose-based chiral stationary phase.
AB  - The binary isotherms of the two enantiomers of Troger's base were measured on a
      system made of pure 2-propanol as the mobile phase and of Chiralpak AD, a chiral
      stationary phase (CSP) based on amylose tri-(3,5-dimethylphenyl carbamate). The
      experimental data were acquired using both frontal analysis and the perturbation
      method. The results obtained are most unusual. The adsorption of the more
      retained (-)-enantiomer is not competitive: the amount adsorbed onto the CSP at
      equilibrium with a constant concentration of the (-)-enantiomer is independent of
      the concentration of the (+) enantiomer. On the other hand, the adsorption of the
      less-retained enantiomer is cooperative: the amount of this (+)-enantiomer
      adsorbed by the CSP at equilibrium with a constant concentration of this
      enantiomer increases with increasing concentration of the (-)-enantiomer. Such a
      phenomenon has hardly ever been reported. A model equation is proposed that
      accounts well for all these isotherm data.

PMID- 12061563
TI  - Separation of chiral sulfoxides by liquid chromatography using macrocyclic
      glycopeptide chiral stationary phases.
AB  - A set of 42 chiral compounds containing stereogenic sulfur was prepared. There
      were 31 chiral sulfoxide compounds, three tosylated sulfilimines and eight
      sulfinate esters. The separations were done using five different macrocyclic
      glycopeptide chiral stationary phases (CSPs), namely ristocetin A, teicoplanin,
      teicoplanin aglycone (TAG), vancomycin and vancomycin aglycone (VAG) and seven
      eluents, three normal-phase mobile phases, two reversed phases and two polar
      organic mobile phases. Altogether the macrocyclic glycopeptide CSPs were able to
      separate the whole set of the 34 sulfoxide enantiomers and tosylated derivatives.
      Five of the eight sulfinate esters were also separated. The teicoplanin and TAG
      CSPs were the most effective CSPs able to resolve 35 and 33 of the 42 compounds.
      The three other CSPs each were able to resolve more than 27 compounds. The normal
      phase mode was the most effective followed by the reversed-phase mode with
      methanol-water mobile phases. Few of these compounds could be separated in the
      polar organic mode with 100% methanol mobile phases. Acetonitrile was also not a
      good solvent for the resolution of enantiomers of sulfur-containing compounds,
      neither in the reversed-phase nor in the polar organic mode. The structure of the
      chiral molecules was compared to the enantioselectivity factors obtained with the
      teicoplanin and TAG CSP. It is shown that the polarity, volume and shape of the
      sulfoxide substituents influence the solute enantioselectivity factor. Changing
      the oxidation state of the sulfur atom from sulfoxides to sulfinate esters is
      detrimental to the compound's enantioselectivity. The enantiomeric retention
      order on the teicoplanin and TAG CSPs was very consistent: the (S)-(+)-sulfoxide
      enantiomer was always the less retained enantiomer. In contrast, the (R)-(-)
      enantiomer was less retained by the ristocetin A, vancomycin and vancomycin
      aglycone columns, showing the complementarity of these CSPs. The macrocyclic
      glycopeptide CSPs provided broad selectivity and effective separations of chiral
      sulfoxides.

PMID- 12061564
TI  - Chromatographic behaviour of selected steroids and their inclusion complexes with
      beta-cyclodextrin on octadecylsilica stationary phases with different carbon
      loads.
AB  - Retention and separation studies of selected estrogens, progestogens and their
      inclusion complexes with beta-cyclodextrin were conducted using two C18 HPLC
      columns with different carbon loads. The difference in carbon load between
      investigated octadecylsilica packing materials was about 50%. The mobile phases
      were composed of a 30% v/v acetonitrile-water mixture without and with addition
      of beta-cyclodextrin at a concentration of 12 mM. The experimental data revealed
      that retention of the steroids was significantly reduced on the column with the
      lower carbon load. Moreover, it was found that this column offers better
      separation power and shorter analysis time at the temperatures studied. However,
      the calculated values of the retention factor ratios (k0(mMCD))/k(12mMCD)) of the
      steroids were similar for both columns investigated. This observation suggests
      that the stationary phase structure appears to have little effect on the
      formation of host-guest complexes if the complexation process is localised to the
      chromatographic mobile phase. From a practical point of view, when the mobile
      phase is modified with beta-cyclodextrin, the separation of the steroids is
      strongly influenced by temperature. The best chromatographic conditions were
      determined for the separation of multicomponent samples on the column with lower
      carbon load. A possible retention mechanism for components of interest in the
      presence of macrocyclic additives is discussed.

PMID- 12061566
TI  - Screening of Catharanthus roseus secondary metabolites by high-performance liquid
      chromatography.
AB  - Two direct HPLC analytical methods for the screening of the major indole
      alkaloids of Catharanthus roseus hairy roots and their iridoid precursors have
      been developed. Photodiode array and fluorescence detection were performed. The
      separation was achieved on a reversed-phase C18 column. The first method allowed
      the separation of catharanthine, serpentine, tabersonine, vindoline, vinblastine,
      and vincristine in 20 min. Ajmalicine, tryptophan, tryptamine and secologanine
      were separated using the second method in 13 min. The identification of the
      compounds was based on the retention time and the comparison of UV spectra with
      those of authentic standards. A simplified alkaloid extraction method was
      developed in order to accelerate sample preparation. The assays were successfully
      used to quantify major compounds of the secondary metabolism of hairy root
      cultures of C. roseus, thus providing a reliable tool for rapid screening of C.
      roseus secondary metabolite samples. In these cultures, ajmalicine, serpentine,
      catharanthine, tabersonine, and tryptamine were detected, but tryptophan,
      vindoline, vinblastine and vincristine were not.

PMID- 12061565
TI  - Amino-bonded silica as stationary phase for liquid chromatographic determination
      of cyclopiazonic acid in fungal extracts.
AB  - A new high-performance liquid (HPLC) chromatographic method is described for
      cyclopiazonic acid (CPA) determination in fungal cultures on a propylamino-bonded
      stationary phase with a CH3CN/CH3COONH4 buffer as mobile phase. Retention of CPA
      on propylamino modified silica under acidic conditions (protonated amino groups
      and deprotonated CPA) is governed by a mixed ion-exchange-reversed-phase
      mechanism. In addition to non-polar (hydrophobic) interactions, polar
      interactions with the surface silanols are also possible and become important as
      the polarity of the mobile phase decreases. A detection limit of 25 pg of CPA
      standard is obtained that represents an improvement of more than two orders of
      magnitude compared to existing HPLC procedures. UV-detector response was linear
      to 200 ng of CPA. Fungal extracts can be analysed after a simple dilution step
      with UV diode array detection that provides peak identity/purity assessment. The
      suitability of the proposed method as a rapid confirmatory test to assess the
      toxigenic potential of different Aspergillus and Penicillium strains is
      demonstrated by the analysis of 54 fungal extracts.

PMID- 12061567
TI  - Theory of liquid chromatography of mono- and difunctional macromolecules. I.
      Studies in the critical interaction mode.
AB  - The theory of liquid chromatography of mono- and difunctional polymers based on
      the model of ideal polymer chain in wide slit-like pores is presented. Analytical
      equations describing chromatographic behavior of functional macromolecules in
      both adsorption, exclusion and critical modes are derived and compared with
      experiments. The focus of this experimental study was on the verification of the
      theory in chromatography at critical conditions. Chromatographic behavior of low
      molar mass end-functionalized polyethylene glycols was found to be in a very good
      qualitative and in a reasonable quantitative agreement with the theory.

PMID- 12061568
TI  - Different elution modes and field programming in gravitational field-flow
      fractionation. IV. Field programming achieved with channels of non-constant cross
      sections.
AB  - Force field programming provided increased speed of separation with an improved
      resolution and detection capability in many field-flow fractionation (FFF)
      techniques. Gravitational field-flow fractionation (GFFF) uses the Earth's
      gravitational field to cause the settlement of particles towards the channel
      accumulation wall. Although this field is constant and relatively weak, there are
      different ways to implement force field programming in GFFF. Because hydrodynamic
      lift forces (HLF) participate in the separation process in focusing (hyperlayer)
      elution mode, they can control the resulting force field acting on particles via
      changes in flow-velocity. These changes can be accomplished by a programmable
      pump or with channels of non-constant cross-sections. This work is focused on
      flow-velocity programming accomplished with channels of non-constant cross
      sections. Three trapezoidal channels of decreasing breadth and two channels of
      decreasing height (along the longitudinal axis) are tested as tools for
      optimization of the separation of a model silica gel particle mixture. The
      trapezoidal channels yielded reduced separation times. However, taking into
      account both speed of separation and resolution, the optimization effect was
      lower compared with the flow-rate gradients generated by a programmable pump. The
      channels of non-constant height did not yield advantageous separations.

PMID- 12061569
TI  - Concurrent validity of the Wechsler abbreviated scale of intelligence and the
      Kaufman brief intelligence test among psychiatric inpatients.
AB  - This study examined the convergent and discriminant validity of the Wechsler
      Abbreviated Scale of Intelligence and the Kaufman Brief Intelligence Test for 85
      psychiatric inpatients. The correlation between the WASI Full Scale and K-BIT
      Composite IQ scores was significant (r = .89, p < .001). Multitrait-multimethod
      analysis of the subtest scores showed that the K-BIT had higher internal
      consistency for its two subtests but, therefore, less differentiation of
      cognitive functioning than the brief Wechsler scale, as would be expected due to
      the larger number and diversity of the latter subtests. Correlations among the
      Wechsler scale subtests were lower than among those for the K-BIT, so the former
      may tap different cognitive functions and yield more clinically useful
      information than the latter. This brief Wechsler scale appears to be a valid
      screening measure of verbal, performance. and general intellectual ability for
      use with an inpatient psychiatric population when considerations of the setting
      or patient preclude administration of a longer measure of intellectual ability.

PMID- 12061570
TI  - Reservations concerning attitudes toward animal research among psychology
      students in Spain.
AB  - Methodological limitations of several items in the 2001 scale used by Navarro, et
      al. are noted and implications discussed.

PMID- 12061571
TI  - Emotional intelligence and prosocial behaviors in adolescents.
AB  - The relationship between emotional intelligence and prosocial behaviors and sex
      differences in 134 adolescents involved in a 6-wk. training camp run by the
      military was investigated. They were asked to evaluate themselves on emotional
      intelligence and randomly chosen peers evaluated them on prosocial behaviors,
      indicated by organizational citizenship behaviors, a measure used in work
      organizations. Ratings of emotional intelligence significantly correlated with
      scores on two of the five organizational citizenship behavior factors: Altruism
      (r = .25, p < .01) and Civic virtue (r = .24, p < .01). The girls scored
      somewhat, but not significantly, higher than the boys on Emotional Intelligence,
      Altruism, Conscientiousness, and Civic virtue, an observation which might be
      explored further.

PMID- 12061572
TI  - Relations of psychological distress with objective individual, family, and
      neighborhood characteristics of urban adolescents.
AB  - This paper describes the relations of psychological distress with 11 ecological
      factors (5 community, 4 family, and 2 individual) among 423 older urban
      adolescents who are predominantly people of color. Data were obtained by means of
      self-report via group-administered questionnaires given between 1994 and 1996;
      most scales are multi-item. There is wide variation in distress. There are very
      few statistically significant relationships between the ecological factors and
      distress, and those are negligible. Girls whose parents have less education and
      live in extended families have higher distress; family and individual domains are
      correlated .04 and .03 with distress and the community domain .00, so this
      ecological model accounts for a mere 7%, of the common total variance in
      distress.

PMID- 12061573
TI  - Clothing interest among Chinese adolescent girls in Hong, Kong in relation to
      socioeconomic status.
AB  - A sample of 358 girls in senior secondary school completed the measures assessing
      importance of clothing and socioeconomic status. A principal component analysis
      indicated a 3-factor solution that explained 51.3% of the total variance in
      scores on the Creekmore Importance of Clothing Questionnaire. The factors were
      named Self-enhancement. Experimentation, and Conformity. A series of one-way
      analyses of variance showed that higher socioeconomic status might account for
      greater experimentation with clothing.

PMID- 12061574
TI  - Extensions of the lost letter technique to divisive issues of creationism,
      darwinism, sex education, and gay and lesbian affiliations.
AB  - Two field studies using 1,004 "lost letters" were designed to test the hypotheses
      that returned responses would be greater in small towns than from a city, that
      addressees' affiliation with a group either (1) opposed to physical education in
      schools, (2) supporting gay and lesbian teachers, or (3) advocating Creationism
      or Darwinism would reduce the return rate. Of 504 letters "lost" in Study A, 163
      (32.3%) were returned in the mail from residents of southeast Louisiana and
      indicated across 3 addressees and 2 sizes of community, addressees' affiLiations
      were not associated with returned responses. Community size and addressees'
      affiliations were associated with significantly different rates of return in the
      city. Return rates from sites within a city were lower when letters were
      addressed to an organization which opposed (teaching) health education in the
      schools than to one supporting daily health education. Of 500 letters "lost" in
      Study B, 95 (19.0%) were returned from residents of northwest Florida and
      indicated across 5 addressees and 2 sizes of community, addressees' affiliations
      were significantly associated with returned responses overall (5 addressees) and
      in small towns (control, Creationism, Darwinism addressees), but not with
      community size. Community size and addressees' affiliations were associated with
      significantly different rates of return in small towns, with returns greater than
      or equal to those in the city (except for the addressee advocating teaching
      Darwinism in public schools). The present findings appear to show that
      applications of the lost letter technique to other divisive social issues are
      useful in assessing public opinion.

PMID- 12061575
TI  - Taxometric analysis of fuzzy categories: a Monte Carlo study.
AB  - A small Monte Carlo study examined the performance of a form of taxometric
      analysis (the MAXCOV procedure) with fuzzy data sets. These combine taxonic
      (categorical) and nontaxonic (continuous) features, containing a subset of casts
      with intermediate degrees of category membership. Fuzzy data sets tended to yield
      taxonic findings on plot inspection and two popular consistency tests, even when
      the degree of fuzziness, i.e., the proportion of intermediate cases, was large.
      These results suggest that fuzzy categories represent a source of pseudotaxonic
      inferences, if on is understood in the usual binary, "either-or" fashion. This in
      turn implies that dichotomous causes cannot be confidently inferred when
      taxometric analyses yield apparently taxonic findings.

PMID- 12061576
TI  - Narcissism and belief in the paranormal.
AB  - The present study was designed to assess whether the relationship between
      narcissistic personality and paranormal belief identified by Tobacyk and Mitchell
      earlier could be replicated with a general population and to see whether the
      effect could be found with a narrower definition of paranormal beliefs that
      focuses only on belief in psychic phenomena. 75 participants completed the
      Narcissistic Personality Inventory and two measures of paranormal belief, the
      Paranormal Belief Scale and the Australian Sheep-Goat Scale. There was no
      correlation between narcissism and Paranormal Belief Scale scores, but narcissism
      and Australian Sheep-Goat Scale scores were significantly positively correlated.
      Of the three subscales to the Australian Sheep-Goat measure, scores for
      narcissism correlated with belief in ESP and PK but not in Life after death.
      These relationships were interpreted in terms of need for control.

PMID- 12061577
TI  - Media coverage of Y2K: content analysis from a single newspaper, 1997 to 2000.
AB  - Content analysis of 258 Year 2000 Y2K-related artides published in a statewide
      newspaper between 1997 and 2000 indicated topics covered and changes over this
      three-year period leading up to 2000.

PMID- 12061578
TI  - Severe traumatic brain injury: some effects on family caregivers.
AB  - This study assesses the effects of severe traumatic brain injuries on family
      members and functioning-a topic of interest for those working with survivors and
      their families. This issue is receiving increased attention as recent findings
      suggest that family adjustment influences outcome for brain-injured persons. The
      Family Environment Scale and the Profile of Mood States were completed by 25
      individuals who had a family member with a severe traumatic brain injury. These
      scales were also completed by a comparison group of 32 individuals who had no
      brain-injured family member. In terms of family functioning, the findings suggest
      that, when a family member suffers a severe traumatic brain injury, depression
      may be elevated, along with a decreased ability to express feelings, decreased
      time and energy for social and recreational activities, and increased control in
      comparison to families without a brain-injured member. While this might
      contribute to family isolation which could last for many years, the overall
      finding of the present study was that caregiver families were coping adequately.

PMID- 12061579
TI  - Perceptions of another person's heavy drinking as a function of one's
      relationship to the drinker a pilot study.
AB  - Of 301 participants in a telephone survey, 201 could identify a problem drinker
      within their social networks. In 67 cases the drinker was a partner, in 45
      another family member, in 61 a friend, and in 28 a work colleague. Another
      person's heavy drinking was reported as most disrupting to one's life when that
      person was a partner or other family member or if one was living in the same
      residence as the drinker. The exception to this was that reported disruption to
      respondents' work life was greatest when the drinker was a work colleague. While
      there appear to be problems for friends and work colleagues, partners and other
      family members appear to report the most disruption so providing services to
      family members seems appropriate.

PMID- 12061580
TI  - PTSD symptoms of mothers following occurrence of a disaster affecting their
      children.
AB  - This study investigated the PTSD symptoms of 37 mothers whose adolescent children
      had been directly involved in a disaster, the Jupiter sinking in 1988. This group
      included mothers whose children were (a) not diagnosed with Posttraumatic Stress
      Disorder and (b) were diagnosed with Posttraumatic Stress Disorder. The measure
      used was the Posttraumatic Stress Disorder Symptom Scale. Women whose children
      were involved in the disaster presented PTSD symptoms. 35% (n = 13) were
      diagnosed with PTSD 3 mo. after the disaster, and 89% (n = 3) of them were
      diagnosed with PTSD 6 yr. afterward. This effect was greater in the subgroup
      whose children had developed traumatic stress disorder following the disaster.

PMID- 12061581
TI  - An evaluation of a required computer-applications course for psychology majors.
AB  - This study describes and evaluates a psychology course specifically focused on
      computer skills for undergraduate psychology majors. Learning by 136
      undergraduates was evaluated on a 57-item objective test. Mean posttest scores
      were significantly higher than the mean pretest scores in all classes across all
      topic areas.

PMID- 12061582
TI  - Murder rates in the regions of Germany.
AB  - Murder rates in the 16 German Bundeslander were associated with marriage, infant
      mortality, unemployment, and suicide rates and with population density.

PMID- 12061584
TI  - Relations of Machiavellian behavior with sales performance of stockbrokers.
AB  - The hypothesis of a relationship between Machiavellian behavior and sales
      performance of Christie and Geis was tested with a sample of 110 stockbrokers.
      Scores on a measure called the Machiavellian Behavior scale were positively and
      significantly correlated with two self-reported measures of sales performance of
      the stock-brokers. Present results together with those of two earlier studies
      supported the hypothesis that salespeople with a Machiavellian orientation are
      likely to be more sucessful. Analysis of the data also indicated predictive
      validity and acceptable internal consistency of the Machiavellian Behavior scale.
      Limitations of the present study and a need for further research are discussed.

PMID- 12061583
TI  - Contrasting the ironic monitoring and motivational explanations of
      postsuppressional rebound.
AB  - Suppressing a thought often results in postsuppressional rebound, that is, a
      subsequent increase in the incidence of the suppressed thought. The present study
      was dcsigned to distinguish between two explanations of rebound: Wegner's 1994
      ironic monitoring theory and Liberman and Forster's 2000 motivational account.
      Participants (99 Deakin University students) first suppressed, then expressed,
      thoughts of a white bear. In some conditions, a delay--presented as occurring
      either intentionally or unintentionally--between suppression and expression was
      introduced. In other conditions, participants concurrently completed a memory
      task and were encouraged to antribute the difficulty of suppression either to
      this task or to the requirement of suppression. An intentional delay, but not an
      unintentional delay, reduced rebound, while attributing difficulty to the
      suppression requirement was associated with greater rebound than was attributing
      it to the memory task. The results are interpreted as supporting Liberman and
      Forster's motivational account of rebound.

PMID- 12061585
TI  - Should subjects be forewarned of the possible psychological consequences of
      filling out a PTSD questionnaire?
AB  - In 1993 Albach investigated the long-term consequences of sexual abuse on
      psychological health. A group of abused women a a control group of nonabused
      women were asked to fill in a questionnaire assessing posttraumatic stress
      disorder (PTSD). For ethical reasons, the abused women were warned that filling
      in the questionnaire might be emotionally stressful. The control group did not
      receive this warning. The abused women scored higher on the questionnaire than
      the nonabused women. The warning they received may have influenced their reports.
      Our experiment investigated this. 101 psychology students were divided into two
      groups, one who received a warning and a control group who did not. The
      hypothesis was that people who had been previously warned would score higher on a
      PTSD questionaire than people who had not. There were, however, no significant
      differences in mean PTSD scores and no known initial differences between groups.

PMID- 12061586
TI  - A comparison of coping factors in Western and non-Western cultures.
AB  - This study presents convergent support for the use of three empirically
      constructed factors, across four samples, from the Ways of Coping Questionnaire.
      Planning, Positive Reappraisal, and Distancing factors were congruent for
      comparisons made between U.S. healthcare workers, Chinese healthcare workers,
      Chinese teachers, and Taiwanese teachers. Additional evidence of congruency was
      provided on specific factors between specific pairs of groups. The results
      support the usage of common factors across languages, cultures, and occupational
      groups but also highlight the importance of not administering a test in a
      different cultural setting without assessing its dimensionality.

PMID- 12061587
TI  - Self-concept and violent delinquency in urban African-American adolescent males.
AB  - African-American adolescent males experience a disproportionate rate of
      victimization associated with and arrest for violent crime. This study examined
      the between self-concept and violent delinquency within a group of 155 urban
      African-American adolescent males. Walter Reckless's 1967 containment theory,
      which suggest that a positive self-concept will insulate a juvenile from
      delinquency and crime, served as the theoretical frame of reference. The
      participants included 155 African-American males aged 13 to 19 years who
      completed the Adolescent Life Survey, developed by the investigators, and the
      Tennessee Self-concept Scale. Quantitative measurments of self-concept and
      delinquency were obtained. In general, the findings did not support containment
      theory. However, the study does present new data regarding serious violent
      delinquency.

PMID- 12061588
TI  - Yoga-based guided relaxation reduces sympathetic activity judged from baseline
      levels.
AB  - 35 male volunteers whose ages ranged from 20 to 46 years were studied in two
      sessions of yoga-based guided relaxation and supine rest. Assessments of
      autonomic variables were made for 15 subjects, before, during, and after the
      practices, whereas oxygen consumption and breath volume were recorded for 25
      subjects before and after both types of relaxation. A significant decrease in
      oxygen consumption and increase in breath volume were recorded after guided
      relaxation (paired t test). There were comparable reductions in heart rate and
      skin conductance during both types of relaxation. During guided relaxation the
      power of the low frequency component of the heart-rate variability spectrum
      reduced, whereas the power of the high frequency component increased, suggesting
      reduced sympathetic activity. Also, subjects with a baseline ratio of LF/HF > 0.5
      showed a significant decrease in the ratio after guided relaxation, while
      subjects with a ratio < or = 0.5 at baseline showed no such change. The results
      suggest that sympathetic activity decreased after guided relaxation based on
      yoga, depending on the baseline levels.

PMID- 12061589
TI  - The Fisher-Pitman permutation test: an attractive alternative to the F test.
AB  - The Fisher-Pitman permutation test is shown to possess significant advantages
      over conventional alternatives when analyzing differences among independent
      samples with unequal variances.

PMID- 12061590
TI  - The Spanish version of the Vividness of Visual Imagery Questionnaire: factor
      structure and internal consistency reliability.
AB  - We examined the factor structure and internal consistency reliability of the
      Spanish version of the Vividness of Visual Imagery Questionnaire which was
      applied to a sample of 850 secondary school students. Factor structure
      investigated by principal components analysis, followed by varimax orthogonal
      rotation, indicated that a single factor explained 37% of the variance. The
      internal consistency of the questionnaire was good (Cronbach alpha=.88). We
      conclude that the Spanish version of the questionnaire, like the English version,
      has a single factor and high internal consistency reliability.

PMID- 12061591
TI  - Tattoos and ratings of personal characteristics.
AB  - High school and university students viewed a photograph of one woman either with
      or without a visible tattoo on her upper arm. They rated the woman on 13 personal
      characteristics (fashionable, athletic, attractive, caring, creative, determined,
      motivated, honest, generous, mysterious, religious, intelligent, artistic).
      Analyses showed ratings of the model with the tattoo were statistically
      significantly lower (more negative) on 9 of the 13 personal characteristics.
      Ratings were not associated with whether the participants had or did not have
      tattoos themselves. Implications for research are discussed, including the need
      to explore the conditions under which negative attitudes may be translated into
      negative behaviors.

PMID- 12061592
TI  - Leaders' anticipated and targets' self-reported resistance to task assignments: a
      replication.
AB  - This is a follow up study of Barbuto's 2000 work in which leaders' ratings and
      targets' self-reported resistance to task assignments are compared. Scores on the
      Anticipated Resistance Indicator among 650 leader-member dyads measure resistance
      based on Barbuto's 1997 five concentric zones of Preference, Indifference,
      Legitimate, Influence, and Noninfluence, examined from both leaders' and targets'
      perspectives. Responses indicated that leaders tend to underestimate followers'
      willingness to perform assigned tasks. In addition, leaders tend to overestimate
      targets' unwillingness to perform undesirable, less enjoyable tasks.

PMID- 12061593
TI  - Immune function and affective states following a natural disaster.
AB  - Although natural disasters sometimes strengthen community ties, it was
      hypothesized that the negative affect following a hurricane would lower
      evaluations of strangers. This hypothesis was tested by having 105 students
      evaluate an individual that they had just met following Hurricane Andrew. The
      hypothesis did not receive support, but students living in storm-damaged
      neighborhoods expressed more negative affect than those living in less damaged
      neighborhoods. Regression analyses also disclosed that severity of a disaster
      predicted concentrations of immunoglobulin A in saliva. The results suggest that
      salivary immunoglobulin A can be used to assess the health consequence of
      disaster exposure.

PMID- 12061594
TI  - Malingering dissociative identity disorder: objective and projective assessment.
AB  - Verification of dissociative identity disorder presents challenges given the
      complex nature of the illness. This study addressed the concern that this
      disorder can be successfully malingered on objective and projective psychological
      tests. 50 undergraduate women were assigned to a Malingering or a Control
      condition, then completed the Rorschach Inkblot Test and the Dissociative
      Experiences Scale II. The Malingering group were asked to simulate dissociative
      identity disorder; controls received instructions to answer all materials
      honestly. Analysis indicated that malingerers were significantly more likely to
      endorse dissociative experiences on the Dissociative Experiences Scale II in the
      range common to patients with diagnosed dissociative identity disorder. However,
      on the Rorschach there were no significant differences between the two groups.
      Results suggest that the assessment of dissociative identity disorder requires a
      multifaceted approach with both objective and projective assessment tools.
      Research is needed to assess these issues in clinical populations.

PMID- 12061595
TI  - Possible barnum effect in the five factor model: do respondents accept random neo
      personality inventory-revised scores as their actual trait profile?
AB  - This study investigated a possible Barnum effect in personality traits, i.e.,
      that persons accept a false trait profile as correct. Having answered the
      Norwegian translation of the NEO Personality Inventory-Revised, a group of 75
      students, 56 (five women military aviation cadets and 19 (10 women) graduate
      students, received a random T-score profile and were asked to rate their
      agreement on a 7-point scale. For all personality traits, i.e., facets and
      domains measured by the NEO Personality Inventory-Revised, positive correlations
      ranging from .08 to .64 were found between the agreement ratings and the
      similarity between the random false scores and the actual scores. The respondents
      identified and rejected random T scores that deviated far from their actual
      scores, which works against the Barnum effect. Correct identification correlated
      negatively with Neuroticism r = -.41) and positively (r = .53) with
      Conscientiousness.

PMID- 12061596
TI  - Stability of the Eysenck Personality Questionnaire for a cross-sectional sample.
AB  - Factor comparability of the Eysenck Personality Questionnaire-Revised was tested
      by contrasting three groups of people: young, adult, and elderly persons.
      Personality trait factors were significantly invariant among age groups. There
      was a significant age x sex interaction for Neuroticism scores.

PMID- 12061597
TI  - Evaluation of Rahim's Organizational Conflict Inventory-II as a measure of
      conflict-handling styles in a sample of Indian salespersons.
AB  - A mail survey of 108 salespersons was conducted to examine their conflict
      handling styles with customers. The Rahim Organizational Conflict Inventory-II
      was used to measure the conflict-handling styles of respondents. An exploratory
      and a confirmatory factor analysis were performed on the items. Analysis
      indicated this is a reliable and valid measure of salespersons' conflict-handling
      styles. Thus, sales researchers can use this measure to examine the conflict
      handling styles of salespersons.

PMID- 12061598
TI  - Comparing auditory vs visual stimuli in the tip-of-the-tongue phenomenon.
AB  - An experiment is reported comparing the effectiveness of auditory and visual
      stimuli in eliciting the tip-of-the-tongue phenomenon. 30 participants were asked
      to name the titles of 27 television shows. Half of the participants were given
      segments of the theme song for each show (auditory cue), and half were shown the
      cast photographs for each show (visual cue). Participants were asked to report
      whenever they experienced the tip-of-the-tongue state. There were no significant
      differences between the auditory and visual stimuli in terms of the incidence
      rate for the tip-of-the-tongue state, the amount of partial information that
      participants provided in their responses, or the frequency of interlopers
      (alternative responses that persistently come to mind). These findings suggest
      that the characteristics of the tip-of-the-tongue state are determined more by
      the nature of the response set than by the type of stimuli used as cues. The
      results are inconsistent with inferential theories of the tip-of-the-tongue
      phenomenon, such as the cue familiarity hypothesis and, instead, tend to support
      direct-access hypotheses.

PMID- 12061599
TI  - Is anti-intellectualism a personality trait?
AB  - In interpreting empirical findings from studies to validate an anti
      intellectualism scale, Eigenberger and Sealander suggest that anti
      intellectualism might be a heritable trait related to "openness to experience."
      This brief article offers a rejoinder, arguing that anti-intellectualism makes
      sense as a cultural perspective that varies by time and place.

PMID- 12061600
TI  - Defining popular iconic metaphor.
AB  - Popular Iconic Metaphor is added to the cognitive linguistic lexicon of
      figurative language. Popular Iconic Metaphors employ real or fictional
      celebrities of popular culture as source domains in figurative discourse. Some
      borders of Popular Iconic Metaphor are identified, and Elvis Presley is offered
      as a prototype example of a popular iconic source domain, due to his ubiquity in
      American popular culture, which affords his figurative usage in ways consistent
      with decision heuristics in everyday life. Further study of Popular Iconic
      Metaphors may serve to illuminate how figurative expressions emerge in their
      localized contexts, structure conduct and experience, and affect mediation of
      cultural and personal meanings.

PMID- 12061601
TI  - A preliminary scale for assessing attitudes toward homosexuals in the military.
AB  - This paper reports a factor analytical study of responses to statements of
      attitudes concerning lesbians and gay men in the military by 72 23.4-yr.-old
      members of the U.S. Marine Corps Reserve. Using exploratory factor analysis with
      an oblique rotation four factors were found which accounted for 64.9% of the
      total common variance. A factor labeled Trust accounted for 40.6% of the common
      variance, Comfort accounted for 8.7%, Acceptance accounted for 8.2%, and the
      fourth factor, Threat, accounted for 7.5%. Cronbach a ranged from .63 to .78.
      Validity was .75 when scores were correlated with those on the Attitudes Toward
      Lesbians and Gay Men scale, supporting the 4-factor interpretation. It is
      recommended that additional factor analyses be performed to further investigate
      the validity of the four factors and that of the entire scale.

PMID- 12061602
TI  - Sex and developmental differences by complexity of functions of occupational
      aspirations of school children across ten years.
AB  - The present longitudinal study examined the complexity of workers' functions for
      65 children's occupational aspirations during a 10-yr. span beginning when the
      children were 7 yr. old and in Grade 2. Every two years through the senior year
      in high school, the children were interviewed, for a total of six interviews. Sex
      and developmental differences in occupational aspirations were examined with
      respect to the focus on Data, People, or Things. Girls (n=31) selected
      occupational aspirations requiring greater complexity in People functions
      throughout the study. From G;rades 2 to 8 boys chose occupations with greater
      complexity of Things and girls chose occupations with greater complexity of Data.
      Developmentally, all children chose increasingly more complex Data occupations
      from Grades 2 to 12. Occupational aspirations in high school showed a decrease in
      the complexity of workers' functions involving People and Things. These
      observations would be expected from social cognitive theory and the 1981 career
      development theory of Gottfredson.

PMID- 12061603
TI  - Relationships among mental health, coping styles, and mood.
AB  - The present study investigated the relationships between mental health (measured
      by the General Health Questionnaire--6 factors: General Illness, Somatic
      Symptoms, Sleep Disturbance, Social Dysfunction, Anxiety and Dysphoria, Suicidal
      Depression), coping styles (two strategies: Cognitive centered, Emotional
      centered), and mood (Tense Arousal, Energetic Arousal). 96 students answered
      questionnaires before their semester test which was a stressor. Analysis showed
      that (1) Tense Arousal scores correlated positively with overall General Health
      scores and all General Health factor scores, and Energetic Arousal scores
      correlated negatively with overall General Health scores and all General Health
      factor scores except one; (2) Anxiety and Dysphoria scores predicted Tense
      Arousal scores the best of General Health factor scores, while both Social
      Dysfunction scores and General Illness scores predicted Energetic Arousal scores.
      (3) Participants with high Energetic Arousal scores used a Cognitive centered
      coping strategy much more than an Emotional centered coping strategy. That is,
      people with low Energetic Arousal scores seem to use the Emotional centered
      coping strategy and have anxiety/dysphoria, while people with high Energetic
      Arousal scores seem to use a Cognitive centered coping strategy and have good
      health and social activity. These results suggest that there are small but
      significant relationships among mental health, coping styles, and mood.

PMID- 12061604
TI  - A demonstration of undergraduate students' first impressions and their ratings of
      pathology.
AB  - An interactive team exercise based in the dual topic areas of social and abnormal
      psychology is described that employs videotaped case studies to sensitize
      students to the processes by which they form first impressions of other people,
      and to various issues regarding assessments of mental disorders. Each of three
      case studies is presented in two parts: Part I simulates a "first impression"
      condition--involving students' ratings of perceived pathology--by briefly showing
      only a patient (no soundtrack present), and Part 2 constitutes a "further
      disclosure" condition by giving more exposure-involving therapists' diagnoses and
      assessments-of the same patient with both sight and soundtrack presented. Data
      are reported from 12 introductory psychology classes in which students (N=367)
      rated the three patients on psychopathology as perceived severity of disorder as
      compared to the actual assessments (also contained on the videotapes) made by
      clinical psychologists and psychiatrists. The demonstration is useful in
      eliciting consistent and predictable first impressions from students, in
      stimulating classroom discussion about the value and accuracy of person
      perceptions and first impressions, and in alerting students to problems related
      to the identification of mental disorders.

PMID- 12061605
TI  - Introversion-extraversion, tempo, and guided imagery.
AB  - This research tested the hypotheses that (a) introverts would produce more vivid
      imagery than would extraverts, and (b) introverts would produce better mental
      imagery if the background auditory tempo was slow, and extraverts would produce
      better mental imagery of the background auditory tempo was fast. Participants
      (N=240) were classified as introverts or extraverts and were randomly assigned
      one of three tempo conditions: slow, fast, or none. They were instructed to form
      mental images while listening individually to one of two stories. Clicks (slow or
      fast) sounded in the background during the stories. All participants then
      completed detailed questionnaires about the vividness of their mental imagery.
      Analysis showed that introverts reported significantly more vividness in their
      imagery than did extraverts. The hypothesized interaction between personality and
      tempo was not found. Implications were drawn for therapeutic applications of
      mental imagery.

PMID- 12061606
TI  - Self-control skills and negative emotional state: a focus on hostility.
AB  - The self-control theory of psychopathology has contributed to the understanding
      and treatment of unipolar depression. This paper explores the relationship
      between self-control skills as measured by the Frequency of Self-reinforcement
      Questionnaire and other negative emotional states, with a focus on hostility. In
      Study 1, scores on the Brief Symptom Inventory were inversely related to self
      control skills among a sample of 53 college students, suggesting potential
      generalizability of the theory. In Study 2, self-control skills were inversely
      related to hostility, anger, and aggression among a sample of 68 college
      students. The role of self-control skills in the regulation of hostility deserves
      further investigation.

PMID- 12061607
TI  - Diminished sense of self-existence and self-reported aggression among Japanese
      students.
AB  - This study examined the relationship between a diminished sense of self-existence
      and self-reported aggression among Japanese undergraduate students. Based on the
      previous scales, 81 items were developed to measure the diminished sense of self
      existence and were assumed to represent three dimensions: self, others, and time.
      286 undergraduate students rated themselves on the Diminished Sense of Self
      existence Scale and the 1992 Buss-Perry Aggression Questionnaire. Analysis
      indicated that men and women had low scores on Verbal Aggression and high scores
      on Hostility with the diminished sense of self-existence. The diminished sense of
      self-existence was not generally related to Anger or Physical Aggression in men,
      whereas in women, Anger and Physical Aggression were found particularly when the
      sense of self-existence in relations with others was diminished.

PMID- 12061608
TI  - Self-reported changes in subjective health and anthrax vaccination as reported by
      over 900 Persian Gulf War era veterans.
AB  - A 1999 study of United Kingdom servicemembers by Unwin, et al. recently found
      significant relationships between anthrax and other vaccinations, reactions to
      those vaccines, and later health problems for male current or former active
      military Gulf War veterans. Likewise, in 2000 Steele and in 1998 Gilroy found
      possible adverse effects of vaccinations on Gulf War veterans. However, the role
      of such vaccinations remains controversial; more recent government reports
      continue to dispute the existence of any data that might reflect adversely on the
      role of vaccinations on the health of Gulf War veterans. To address this
      controversy, the current study assessed similar relationships for over 900
      Reserve Component Gulf War Era veterans from Ohio and nearby states. Gulf War
      veterans were more likely to report poorer health than non-Gulf veterans. Female
      veterans were more likely to report mild or severe reactions to vaccines than
      male veterans. Those veterans who received anthrax vaccine reported more
      reactions to vaccines than those who did not receive anthrax vaccine. Declines in
      long-term subjective health were associated with receipt of anthrax vaccine by
      Gulf War veterans but not for those who did not deploy to the Gulf, although few
      of the latter received anthrax vaccine. Regardless of deployment status, veterans
      who reported more severe reactions to vaccines were more likely to report
      declines in subjective health. Female veterans reported poorer health during the
      Gulf War than did male veterans, but sex was not related to veterans' reports of
      subjective health at subsequent times. It is recommended that servicemembers who
      experience severe reactions to anthrax vaccine be medically reevaluated before
      receiving further anthrax vaccine and that careful follow-ups be conducted of
      those receiving the vaccine currently, in accordance with Nass's 1999
      recommendations. We also recommend that safer alternatives to thimerosal (a
      mercury sodium salt, 50% mercury) be used to preserve all vaccines.

PMID- 12061609
TI  - Age, sex, education, religion, and perception of tattoos.
AB  - Tattooing has become more acceptable in the mainstream American culture in recent
      years. Based on a survey with face-to-face interviews of 335 nontattooed adults
      randomly selected from a city with a population of 444,000, this study explored
      the relationship of individuals' demographic variables, attitudes toward
      religion, and their perceptions of tattoos. The hierarchical multiple regression
      analysis showed that age and attitude toward religion were associated with
      individuals' perception of tattoos.

PMID- 12061610
TI  - Role models in self-esteem of college women.
AB  - This study examined the relationship between self-esteem and the existence of
      role models among a sample of 36 female college students. Participants completed
      a questionnaire which included demographic questions, the Self-esteem Inventory,
      and questions concerning use of childhood and contemporary role models.
      Independent t-test results indicated that participants who reported having
      current role models had higher self-esteem scores than participants who did not,
      suggesting that role models may contribute to higher self-esteem in college-age
      women. No significant differences in self-esteem were by sex of the role model.

PMID- 12061611
TI  - Order effects in research on paranormal belief.
AB  - Measures of paranormal belief and emotional intelligence were given a group of 72
      college students using Tobacyk's Revised Paranormal Belief Scale and Schutte,
      Malouff, Hall, Haggerty, Cooper, Golden, and Dornheim's Emotional Intelligence
      Scale. Order effects indicated that participants who took the Paranormal Belief
      Scale first had lower emotional intelligence scores than those who took the
      Emotional Intelligence Scale first. The study demonstrates the importance of
      taking order effects into account when conducting research on paranormal belief.

PMID- 12061613
TI  - Reliability of estimates of return rates as a measure of public attitudes to
      violence.
AB  - An analysis of letters placed in Mobile, Alabama and Sioux Falls, South Dakota
      (ns = 500 and 600) showed return rates among the several addresses were
      essentially uncorrelated (rs = -.11 to .08) so interpoll reliability is lacking.

PMID- 12061612
TI  - Self and other ratings of Canadian and Korean groups of mental health
      professionals and their clients.
AB  - Taylor and Brown's concept of positive illusions (1988) was examined in two
      studies. It was predicted that more mentally healthy professional helpers (n=
      103) than less mentally healthy clients (n=89) (a) view themselves in more self
      aggrandizing, positive terms and (h) hold a more optimistic view of their future.
      Two groups of participants from two culturally different settings, i.e., Canada
      and Korea, completed questionnaires assessing self-description of personality and
      view of their own futures. Analysis supported predictions for both Canadian and
      Korean samples. Implications of the study are discussed.

PMID- 12061614
TI  - Tainted love: content analysis of documents written by accused spousal abusers to
      their victims.
AB  - This study analyzed themes in documents written by 22 male accused spousal
      abusers to their female victims. Using Pence's Power and Equity model (1998), 86%
      of the themes denied equity and expressed power and control in the relation. Of
      these, 28% minimized or denied the abuse, 24% used the children to manipulate the
      victim, 16% showed disrespect for the victim, and 14% invoked male privilege
      (including God's ordination of the abusive relation). These hallmarks of tainted
      love are rooted in the desire of the accused abuser to maintain power and control
      over the victim.

PMID- 12061615
TI  - Relation of transliminality and sensation seeking.
AB  - The Revised Transliminality Scale and Zuckerman's Sensation Seeking Scale (Form
      V) were administered to 83 psychology undergraduates. Weak positive correlations
      suggested that participants scoring high on the Transliminality Scale tended to
      be more experience seeking and, overall, more inclined to score sensation
      seeking.

PMID- 12061616
TI  - Psychometric properties of a kindergarten behavior rating scale to predict later
      academic achievement.
AB  - The design and description of the psychometric properties of a Kindergarten
      Behavior Rating Scale used to predict later academic achievement were based on a
      survey of past literature on efficient predictors of school failure which
      indicated a need for a scale that identifies kindergarten pupils who are at risk
      for school failure during their elementary education. The scale, developed over a
      3-yr. period, significantly predicted academic achievement in reading, writing,
      and mathematics, as indicated by correlations, .15 and .66 between scores on the
      scale and academic achievement in Grades 1 and 2. Use of judgment by kindergarten
      teachers to assess risks was also considered, as are other suggestions and
      limitations on the further use.

PMID- 12061617
TI  - Furnham's Money Attitude Scale.
AB  - An item-analysis of responses from 186 undergraduates to the Money Attitude Scale
      developed by Furnham did not replicate the factor pattern which he derived.

PMID- 12061618
TI  - Sex differences in perceived outcomes of electronic mail interactions.
AB  - Researchers have found that sex plays a crucial role in perceptions of usability,
      graphical accents, and general satisfaction within computer-mediated
      interactions. 192 students (71 men and 121 women) responded to 12 items taken
      from the Electronic Mail Outcome Scale related to their perceived
      Appropriateness, Effectiveness, and Satisfaction obtained through electronic mail
      interactions. Analysis indicated no significant differences between men and women
      in reference to either Effectiveness or Satisfaction; however, women were more
      sensitive to social expectations within electronic mail interactions than men.

PMID- 12061619
TI  - Will the truth come out? the effect of deception, age, status, coaching, and
      social skills on CBCA scores.
AB  - The impact of Veracity, Age, Status (witness or suspect), Coaching (informed or
      uninformed regarding CBCA), and Social Skills (social anxiety, social adroitness,
      and self-monitoring) on Criteria-Based Content Analysis scores was examined.
      Participants (aged 5-6, 10-11, 14-15, and undergraduates) participated in a
      "rubbing the blackboard" event. In a subsequent interview they told the truth or
      lied about the event. They were accused of having rubbed the blackboard
      themselves (suspect condition) or were thought to have witnessed the event
      (witness condition), and were or were not taught some CBCA criteria prior to the
      interview. CBCA scores discriminated between liars and truth tellers in children,
      adults, witnesses, and suspects. However, truth tellers obtained higher CBCA
      scores than liars only when the liars were uninformed about CBCA. CBCA scores
      were correlated with social skills. It is argued that thesefindings should
      caution those who believe that the validity of CBCA has been conclusively
      demonstrated.

PMID- 12061621
TI  - Punitive damage decision making: the decisions of citizens and trial court
      judges.
AB  - Some states have allocated the authority to determine the amount of punitive
      damages to judges rather than to juries. This study explored the determination of
      damages by jury-eligible citizens and trial court judges. The punitive damage
      awards of both groups were of similar magnitude and variability. The compensatory
      damages ofjurors were marginally lower but, in some conditions, were more
      variable than the compensatory damage awards of judges. Both groups appropriately
      utilized information about both the actual and potential severity of the harm to
      the plaintiff in determining punitive damages and used only the actual severity
      of the injury in determining compensatory damages. The punitive damage awards of
      both groups were influenced by the wealth of the defendant, but the compensatory
      damage awards of judges were marginally more influenced by defendant wealth than
      those of citizens. The results are discussed in the context of proposals for
      punitive damages reform.

PMID- 12061620
TI  - Understanding children's use of secrecy in the context of eyewitness reports.
AB  - To investigate socioemotional influences on children's eyewitness accuracy, we
      examined children's reports for activities they were motivated to conceal. Forty
      eight 3-6-year-old children participated in a standardized play session with
      their mothers. Half of the children were told by an experimenter not to play with
      certain toys, but did so at the urging of their mothers, who told their children
      to keep the play activities secret. The remaining children were not restricted
      from playing with the toys, nor told by their mothers to keep the play activities
      secret. Later, all children were interviewed about the activities with free
      narrative and detailed questions. Half were given an interview that consisted of
      highly suggestive questions; half were given an interview consisting of specific,
      less suggestive questions. Results indicated that older children who were
      instructed to keep events secret withheld more information than did older
      children not told to keep events secret. Younger children's reports were not
      significantly affected by the secret manipulation. There were no significant
      effects associated with interview type. We discuss implications for understanding
      the development of children's knowledge and use of secrecy, and applications of
      the research to issues that arise when child witnesses give reports in legal
      contexts.

PMID- 12061622
TI  - The effect of competency restoration training on defendants with mental
      retardation found not competent to proceed.
AB  - The present investigation focused on the reevaluations of "competency to stand
      trial" (CST) of 75 criminal defendants with mental retardation (MR) who were
      originally found incompetent and who were referred for treatment. The effect of
      competency restoration training was examined. Site of training was also
      investigated. Because habilitation facilities are specially designed to help
      individuals with MR, it was suspected that training at habilitation centers would
      have a greater effect on restoration of defendants with MR than the training at
      state hospitals. Results showed that significantly more defendants did not gain
      competency following training than those who did. Analysis revealed that (a)
      higher IQ and (b) being African American rather than Caucasian American were
      predictive of restoration. When discriminating factors were held constant, site
      of training did not significantly affect competency restoration. Possible
      explanations for this finding were discussed.

PMID- 12061623
TI  - Effects of testimonial inconsistencies and eyewitness confidence on mock-juror
      judgments.
AB  - This study examined the interaction between testimonial consistency and
      eyewitness confidence on mock-jurors' judgments of probability that the defendant
      committed the crime and verdicts. In a 2 (testimonial consistency) x 2
      (confidence) between-groups design, 130 mock-jurors listened to an audio-taped
      trial of a person charged with armed robbery. Manipulations were contained in the
      prosecution witness's responses to detailed questioning by prosecution and
      defense attorneys. Although consistency is considered to be a key marker of
      accuracy, its impact on judgments was weak and nonsignificant. Witness confidence
      had a strong influence on judgments, whether testimony was consistent or
      inconsistent. We suggested that witness confidence may be more likely to emerge
      as a dominant influence on juror judgments when the testimony is wide ranging
      rather than relatively brief and concerned only with a specific issue (e.g.,
      identification confidence).

PMID- 12061624
TI  - Suspects, lies, and videotape: an analysis of authentic high-stake liars.
AB  - This study is one of the very few, and the most extensive to date, which has
      examined deceptive behavior in a real-life, high-stakes setting. The behavior of
      16 suspects in their police interviews has been analyzed. Clips of video footage
      have been selected where other sources (reliable witness statements and forensic
      evidence) provide evidence that the suspect lied or told the truth. Truthful and
      deceptive behaviors were compared. The suspects blinked less frequently and made
      longer pauses during deceptive clips than during truthful clips. Eye contact was
      maintained equally for deceptive and truthful clips. These findings negate the
      popular belief amongst both laypersons and professional lie detectors (such as
      the police) that liars behave nervously by fidgeting and avoiding eye contact.
      However, large individual differences were present.

PMID- 12061625
TI  - Advance in treatment strategy and immune reconstruction against HIV-1 infection.
AB  - HIV-1 can be considered an infection of the immune system, resulting in
      progressive and ultimately profound immune suppression. The availability of
      highly active antiretroviral therapy (HAART) has resulted in dramatic changes in
      the disease course in persons fortunate enough to have access to these
      medications, but long-term therapy is limited by the development of resistance as
      well as toxicities of the potent medication regimens. Emerging data indicate that
      individuals who have non-progressive clinical course control HIV-1
      immunologically. This has bolstered hope that the immune response might be
      effectively augmented in persons with HIV infection. Recent data indicating that
      immediate treatment of acute infection leads to augmentation of antiviral immune
      responses have provided evidence that the immune system might be enhanced in
      certain situations. Therefore, investigation in the reconstitution of anti-HIV
      immune response in patients under HAART should provide encouragement for
      continuing to explore methods to obtain meaningful and durable immune enhancement
      as an adjunct to HAART in HIV-1 infection.

PMID- 12061626
TI  - Phylogenetic analysis of spotted fever group Rickettsiae isolated from ticks in
      Japan.
AB  - Eight spotted fever group (SFG) rickettsiae isolated from ticks in Japan were
      classified by phylogenetic analysis based on the nucleotide sequences of both the
      citrate synthase-encoding gene (gltA) and 190-kDa antigen-encoding gene (rOmpA).
      In the phylogenetic tree of gltA, strains DT-1 and FLA-1 isolated from the
      Dermacentor taiwanensis and Haemaphysalis frava ticks, respectively, were placed
      as Rickettsia japonica, and strains IO-1, IO-2, IO-25, IM-1 and IP-2 from genus
      Ixodes ticks were placed as Rickettsia helvetica. Strain AT-1 isolated from the
      Amblyomma testudinarium belonged to the cluster including Rickettsia akari,
      Rickettsia australis and Rickettsia felis. In the phylogenetic tree of the rOmpA,
      strains DT-1 and FLA-1 were placed as R. japonica, and strain AT-1 belonged to
      the cluster including Rickettsia cooleyi and the symbiont of Ixodes scapularis.
      The rOmpA fragments of 5 Ixodes isolates could not be amplified by PCR. The
      present study showed that strains DT-1 and FLA-1 were genotypically identical to
      R. japonica, and 5 Ixodes isolates were associated with the R. helvetica. Based
      on previous genotypic and antigenic data, and the phylogenetic analysis presented
      here, strain AT-1 should be considered as a new species among SFG rickettsiae.

PMID- 12061627
TI  - Inhibition by apple polyphenols of ADP-ribosyltransferase activity of cholera
      toxin and toxin-induced fluid accumulation in mice.
AB  - The effects of crude polyphenol extracted from immature apples on the enzymatic
      and biological activities of a cholera toxin (CT) were investigated. When the
      apple polyphenol extract (APE) was examined for properties to inhibit CT
      catalyzed ADP-ribosylation of agmatine, it was found that APE inhibited it in a
      dose-dependent manner. The concentration of APE to inhibit 50% of the enzymatic
      activity of CT (15 microg/ml) was approximately 8.7 microg/ml. The APE also
      diminished CT-induced fluid accumulation in two diarrhea models for in vivo mice.
      In the ligated ileum loops, 25 microg of APE significantly inhibited fluid
      accumulation induced by 500 ng of CT. In a sealed mouse model, even when APE was
      administered orally 10 min after a toxin injection, fluid accumulation was
      significantly inhibited at a comparable dosage. Lineweaver-Burk analysis
      demonstrated that APE had negative allosteric effects on CT-catalyzed NAD:
      agmatine ADP-ribosyltransferase. We fractionated the APE into four fractions
      using LH-20 Sephadex resin. One of the fractions, FAP (fraction from apple
      polyphenol) 1, which contains non-catechin polyphenols, did not significantly
      inhibit the CT-catalyzed ADP-ribosylation of agmatine. FAP2, which contains
      compounds with monomeric, dimeric, and trimeric catechins, inhibited the ADP
      ribosylation only partially, but significantly. FAP3 and FAP4, which consist of
      highly polymerized catechin compounds, strongly inhibited the ADP-ribosylation,
      indicating that the polymerized structure of catechin is responsible for the
      inhibitory effect that resides in APE. The results suggest that polymerized
      catechin compounds in APE inhibit the biological and enzymatic activities of CT
      and can be used in a precautionary and therapeutic manner in the treatment of
      cholera patients.

PMID- 12061628
TI  - Characterization of spotted fever group rickettsiae detected in dogs and ticks in
      Okinawa, Japan.
AB  - Spotted fever group (SFG) rickettsial DNAs were detected in 2.4% of 340 canine
      blood samples and a pool of 84 tick pool samples (229 ticks) collected in
      Okinawa, Japan by PCR using a citrate synthase and an SFG rickettsial 190-kDa
      surface antigen gene primer pair. The sequences of both genes from canine blood
      and tick samples showed high levels of similarity with those of
      Rickettsiajaponica and several SFG rickettsiae (R. aeschlimannii, R. massiliae,
      R. rhipicephali and Bar-29 strain). Phylogenesis of canine blood and tick samples
      was closely related to that of reference SFG rickettsiae. Serological evidence of
      SFG rickettsial infection in dogs and humans in Okinawa, where no clinical human
      cases have been reported, has been obtained. In this study, genetical
      characterization of SFG rickettsia in Okinawa was investigated phylogenetically.

PMID- 12061629
TI  - Mycoplasmal lipoproteins induce toll-like receptor 2- and caspases-mediated cell
      death in lymphocytes and monocytes.
AB  - Lipoproteins of Mycoplasma salivarium and Mycoplasma fermentans preferentially
      induced necrotic cell death in lymphocytic cell lines, MOLT-4 and Raji, and in
      one monocytic cell line, THP-1, whereas they preferentially induced apoptotic
      cell death in another monocytic cell line, HL-60. These findings were also
      supported by ultrastructural observations by the use of scanning and transmission
      electron microscopes and by agarose gel electrophoresis of the genomic DNA. The
      lipoproteins activated caspase-3 in both MOLT-4 and HL-60 cells, which was
      assessed by the cleavage of the synthetic substrate DEVD-pNA and the endogenous
      substrate poly(ADP-ribose) polymerase. The cytotoxicity to MOLT-4 and HL-60 cells
      was inhibited by various caspase inhibitors, Ac-DMQD-CHO, Ac-IETD-CHO, and Z-VAD
      FMK. The cytotoxicity was also partially suppressed by the monoclonal antibody to
      Toll-like receptor 2. Thus this study demonstrated that mycoplasmal lipoproteins
      induce caspases-dependent necrotic and apoptotic cell death in lymphocytes and
      monocytes/macrophages, which is partially induced by TLR2-mediated signaling.

PMID- 12061630
TI  - An outbreak of neonatal toxic shock syndrome-like exanthematous disease (NTED)
      caused by methicillin-resistant Staphylococcus aureus (MRSA) in a neonatal
      intensive care unit.
AB  - Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a new entity
      of methicillin-resistant Staphylococcus aureus (MRSA) infection. Most of NTED
      cases reported previously in the literature were sporadic ones. In the present
      report, we describe an outbreak of NTED that occurred in a neonatal intensive
      care unit (NICU) between April, 1999 and April, 2000 in Japan. All MRSA strains
      isolated from 14 patients (6 NTED, 2 infections and 6 colonizations) in this
      outbreak belonged to the group of coagulase II and produced toxic shock syndrome
      toxin 1 (TSST-1). Of these, 14 strains produced staphylococcal enterotoxin C
      (SEC). No other superantigenic toxins were produced by these strains. The pulsed
      field gel electrophoresis (PFGE) patterns of genomic DNA digested with SmaI were
      indistinguishable each other due to no band shifting in all of the 13 strains
      except for strain O-21 and M56. Strain M56 was different from the dominant type
      in the positions of only 2 bands, whereas the pattern of strain O-21 had no
      similarity with the other pattern, suggesting that this outbreak was associated
      with the spread of a unique MRSA strain in the NICU. Two-dimensional
      electrophoresis (2-DE) analysis of exoproteins revealed that the patterns of
      these 14 strains were very indistinguishable to each other, and that these
      strains produced very large amounts of TSST-1 and SEC3 subtype superantigens, as
      measured with computer-assisted image analysis of the intensity of 2-DE spots.
      The 2-DE gel of O-21 showed the different pattern from the others. These results
      as well as the profiles of toxin production also supported the conclusion drawn
      from PFGE analysis. Based on these results, the involvement of TSST-1 and SEC3 in
      the pathogenesis of NTED is discussed.

PMID- 12061632
TI  - Adhesion of lactic acid bacteria to caco-2 cells and their effect on cytokine
      secretion.
AB  - Cytokines secreted by human enterocytes play a critical role in mucosal and
      systemic immunity. Intestinal microorganisms can influence this secretion. In the
      present study, 30 strains of lactic acid bacteria were characterized for their
      adhesion to Caco-2 cells and their potential to stimulate proinflammatory
      cytokine secretion by this cell line. The bacteria adhered in a strain-dependent
      manner to Caco-2 cells. Contact with lactobacilli did not result in the
      production of IL-6 or IL-8. A slight IL-6 and IL-8 production by a Caco-2 cell
      was detected after exposure to 8 of the tested Bifidobacterium strains. No
      correlation was found between adhesion and cytokine induction among the bacteria
      tested. This indicates that lactic acid bacteria, even those with strong adhesive
      properties, are not very likely to trigger an inflammatory response in human
      enterocytes.

PMID- 12061631
TI  - Persistent parapoxvirus infection in cattle.
AB  - The possibility of persistent parapoxvirus (PPV) infection was investigated by
      serologically and genetically using cattle infected with the virus experimentally
      and naturally. Three cattle were inoculated with the virus subcutaneously at
      several spots in the lips and abdominal regions. Small papules developed in the
      inoculated regions, and antibodies to the virus developed and continued
      persistently. One animal, from which one PPV had been previously isolated, was
      also subjected to serological and viral detection tests as a naturally infected
      case. Two of these four cattle were injected with dexamethasone (DM), and one was
      injected with interferon-gamma (IFN-gamma). The viral genome was rarely detected
      from the peripheral blood leukocytes in the ordinary condition, but frequently
      when the animals were injected with IFN-gamma. The viral genome was also detected
      from the lymph nodes as these PPV infected animals were euthanized. These results
      indicated that cattle were infected with PPV subclinically and persistently, and
      the virus was activated in stressed or immunosuppressed animals. The virus would
      be harbored in the lymphotic tissues of the animals when they show no clinical
      symptoms.

PMID- 12061633
TI  - Purification of a serine protease of Vibrio parahaemolyticus and its
      characterization.
AB  - A 50 kDa protease designated as VPP1 was purified from the culture supernatant of
      a clinical strain of Vibrio parahaemolyticus by ammonium sulfate fractionation,
      Sephacryl S-200 HR gel filtration and Fractogel EMD TMAE 650 ion-exchange
      chromatography. VPP1 was inhibited by EDTA, EGTA and serine protease inhibitors,
      suggesting that it is a calcium-dependent serine protease. N-terminal amino acid
      sequence of VPP1 was quite similar to that of V. metschnikovii protease and
      antibody against VPP1 inhibited the activity of V. metschnikovii protease,
      suggesting the similarity of the two proteases. It was demonstrated that VPP1 or
      its related protease widely distribute in not only V. parahaemolyticus but also
      V. alginolyticus.

PMID- 12061634
TI  - The serologic response to Salmonella enteritidis and Salmonella typhimurium in
      experimentally infected chickens, followed by an indirect lipopolysaccharide
      enzyme-linked immunosorbent assay and bacteriologic examinations through a one
      year period.
AB  - Three groups of 100 individually marked salmonella-free chickens were followed
      for a period of 53 wk. The chickens were infected as day olds by crop
      instillation of 10(8) colony-forming units: one group with Salmonella enteritidis
      and a second group with Salmonella typhimurium. A third group was kept uninfected
      as controls. The groups were monitored bacteriologically by examination of
      cloacal swabs and organs and serologically by examination of serum and egg yolk
      by a lipopolysaccharide enzyme-linked immunosorbent assay throughout the period.
      Within the first week, 100% of birds in both infected groups were excreting
      salmonella bacteria in the feces. However, the number of fecal excretors declined
      rapidly with time, down to 6% in 16 wk for S. typhimurium and down to a similar
      level within the first 8 wk for S. enteritidis. For the latter, relapses with up
      to 40% positive birds were observed at the onset of egg production. For both S.
      typhimurium and S. enteritidis, positive bacteriologic cultures were obtained by
      sampling from internal organs at the end of the experiment, more than 1 yr from
      the time of infection. At the age of 6-7 wk, 50% of the chickens in the two
      infected groups showed a measurable serologic response in serum samples. The
      response persisted throughout the study in both serum and egg yolk samples. The
      inclusion of serologic methods is a valuable additional tool in the detection of
      salmonella in poultry, but serology should be used in conjunction with
      bacteriologic methods in surveillance programs, in particular to detect flocks in
      early stages of infection before a measurable serologic response has been raised.

PMID- 12061635
TI  - Effect of in ovo vaccine delivery route on herpesvirus of turkeys/SB-1 efficacy
      and viremia.
AB  - A study was designed to ascertain the influence of in ovo site of inoculation and
      embryonic fluid type on the development of Marek's disease (MD) vaccine viremia
      and efficacy against MD challenge. The experiments were divided into in vitro and
      in vivo phases. In the in vitro phase, herpesvirus of turkeys/SB-1 vaccine was
      combined with basal medium eagle (BME) medium (control), amniotic fluid, or
      allantoic fluid and subsequently titrated on secondary chick embryo fibroblast
      cultures. There were no significant differences in titer between the virus
      inoculum carried in BME and the virus inoculum combined with either the allantoic
      fluid or the amniotic fluid. In the in vivo phase, five routes of inoculation,
      amniotic, intraembryonic, allantoic, air cell, and subcutaneous at hatch, were
      compared for generation of protection against virulent MD challenge. Comparisons
      were made in both specific-pathogen-free and commercial broiler embryos/chicks
      and, for the amniotic and allantoic routes, injection at either day 17 or day 18
      of embryonation. Reisolation of the vaccine virus at day 3 of age was also done
      for all routes with the exception of the air cell route. Vaccine virus was
      recovered from all birds tested that were injected in ovo via the amniotic and
      intraembryonic routes and the subcutaneously at hatch route but was isolated only
      sporadically from birds inoculated via the allantoic route. Vaccination
      protective efficacy against virulent MD for all birds vaccinated in ovo via the
      amniotic or intraembryonic routes and birds vaccinated subcutaneously at hatch
      was over 90% regardless of day of in ovo injection or bird type. Protective
      efficacy for vaccines delivered in ovo by either the allantoic or the air cell
      routes was less than 50% regardless of day of injection or bird type. Therefore,
      in ovo MD vaccines must be injected either via the amniotic route or the
      intraembryonic route for optimal performance.

PMID- 12061636
TI  - High virus titer in feather pulp of chickens infected with subgroup J avian
      leukosis virus.
AB  - Subgroup J avian leukosis viruses (ALVs), which are a recombinant virus between
      exogenous and endogenous ALVs, can spread by either vertical or horizontal
      transmission. Exogenous and endogenous ALVs can be detected in feather pulp. In
      this study, virus titers in feather pulp of chickens infected with subgroup J ALV
      were compared with those of plasma and cloacal swab. All of the broiler chickens
      inoculated with subgroup J ALV at 1 day old were positive for virus from feather
      pulp during the experimental period of between 2 wk and 8 wk of age. Virus titers
      in feather pulp of some broiler chickens infected with subgroup J ALV were very
      high, ranging from 10(7) to 10(8) infective units per 0.2 ml. Virus titers in
      feather pulp were usually the highest among the samples of plasma, cloacal swab,
      and feather pulp tested. In another experiment in which layer chickens were
      inoculated with subgroup J ALV at 1 day old, virus was detected in feather pulp
      from 2 wk until 18 wk of age, and virus persisted longer in feather pulp than in
      plasma. Almost all of the layer chickens tested were positive for virus by
      polymerase chain reaction (PCR) with DNA extracted from feather pulp samples at
      2, 4, and 10 wk of age, and the PCR from feather pulp was more sensitive than
      virus isolation from plasma, cloacal swab, and feather pulp. All above results
      indicate that samples of feather pulp can be useful for virus isolation and PCR
      to confirm subgroup J ALV infection.

PMID- 12061637
TI  - Safety, immunogenicity, and efficacy of two Escherichia coli cya crp mutants as
      vaccines for broilers.
AB  - Attenuated derivatives (delta cya delta crp mutants) of an O2 and an O78 avian
      septicemic Escherichia coli strain were used to immunize broiler chickens by
      spray to determine the safety, immunogenicity, and efficacy of the derivatives in
      single- and double-dose regimens. In the safety and immunogenicity studies,
      groups of 10 chickens were vaccinated by spray (droplet size approximately 20
      microm) with the parent E. coli, the mutant organisms, or phosphate-buffered
      saline (PBS) at 14 days of age and euthanatised 21 days later. There was no
      deaths or gross pathologic finding in any of the chickens immunized with the
      vaccine strains. Compared with the levels in chickens exposed to PBS, there were
      significantly higher levels of immunoglobulin (Ig) G antibody in serum and air
      sac washings and of IgA antibody in air sac washings in response to the virulent
      parent strains than to the vaccine strains. In efficacy studies, chickens were
      immunized with the O2 or the O78 vaccine strain or PBS at day 14 and with the O2
      vaccine strain or PBS at days 10 and 14 and challenged with the parent strain 10
      days after the last vaccination. There was no significant difference in local IgA
      and IgG and serum IgG responses between vaccinated and control groups. Chickens
      vaccinated with the O2 strain, but not the O78 strain, had significantly lower
      air sac lesion scores compared with those of the unvaccinated groups in both
      single- and double-dose regimens. We conclude that the mutant O2 strain provided
      moderate protection against airsacculitis.

PMID- 12061638
TI  - Avian influenza virus subtypes inside and outside the live bird markets, 1993
      2000: a spatial and temporal relationship.
AB  - Between 1993 and 2000, gallinaceous birds, waterfowl, and environmental specimens
      from the live bird markets (LBMs) of the northeastern United States and non-LBM
      premises were tested for the presence of avian influenza virus (AIV), pathogenic
      properties of AIV subtypes, especially of hemagglutinin (H) subtypes H5 and H7,
      and a possible association between LBM and non-LBM infections. Ten H subtypes of
      AIV were isolated from the LBM specimens: H1, H2, H3, H4, H5, H6, H7, H9, H10,
      and H11. During this period, the 10 subtypes also were isolated from birds in non
      LBM premises. In the LBMs, subtypes H2, H3, H4, H6, H7, and H11 were present for
      5-8 yr despite efforts to clean and disinfect the premises. The H5 or H7 subtypes
      present during the same year in both LBMs and non-LBMs within a state or in
      contiguous states were (subtype/year): H5N2/1993, 1999, and H7N2/1994-99. The AIV
      subtypes including the H5 and H7 that were evaluated for pathogenicity in
      chickens were low pathogenic. The deduced amino acid sequence at the H cleavage
      site of H5 and H7 subtypes was consistent with those of low pathogenic AIV.
      Although the H5N2 and H7N2 subtypes remained low pathogenic, they did undergo
      mutations and acquired an additional basic amino acid at the H cleavage site;
      however, the minimum number of basic amino acids in correct sequence (B-X-B-R,
      where B = basic amino acid, X = need not be basic amino acid, and R = arginine)
      required for high pathogenicity was lacking. A low pathogenic H5 or H7 subtype
      may become highly pathogenic by acquiring additional basic amino acids at the H
      cleavage site. The LBMs have been and will likely continue to be a source of AIV
      for commercial poultry.

PMID- 12061639
TI  - Latency sites and reactivation of duck enteritis virus.
AB  - Duck virus enteritis (DVE) is a contagious disease caused by herpesvirus in
      waterfowl populations. Recovered birds become carriers and shed the virus
      periodically. Reactivation of latent duck enteritis virus (DEV) has been
      implicated in outbreaks of DVE in domestic and migrating waterfowl populations.
      In this study, the sites for virus latency were determined in white Pekin ducks
      infected with the DEV-97 strain. At 3 wk postinfection, infectious virus was not
      detectable in tissues or cloacal swabs (CSs). At 7 and 9 weeks postinfection, the
      viral DNA was detected by polymerase chain reaction in the trigeminal ganglia
      (TG), suggesting that the virus is latent. Viral DNA was detected in the
      peripheral blood lymphocytes (PBL), spleen, thymus, bursa, and CSs only after in
      vitro cocultivation. In vivo virus reactivation was demonstrated when
      dexamethasone or a combination of dexamethasone and cyclophosphamide was
      inoculated in latently infected ducks. The reactivation of DEV occurred without
      any clinical evidence of the disease, but the virus was detected in PBL and CSs.
      We conclude from this study that DEV establishes latency in TG and lymphoid
      tissues including PBL.

PMID- 12061640
TI  - Marek's disease in turkeys. I. A seven-year survey of commercial flocks and
      experimental infection using two field isolates.
AB  - Marek's disease virus (MDV) causes immunosuppression and tumors in chickens, but
      the turkey is an unusual host for the virus, and tumors caused by MDV in turkeys
      are unique. We describe the prevalence of turkey tumors in Israel between 1993
      and 2000, their molecular diagnosis by polymerase chain reaction (PCR), and the
      natural distribution of herpesvirus of turkeys (HVT). Most clinical cases with
      tumors in commercial turkeys were diagnosed as MDV. The reproduction of Marek's
      disease (MD) in turkeys by two turkey MDV strains, Ar and La, was analyzed, and
      it was shown that these strains can induce tumors in experimental trials. The
      severity of experimental disease differed from those features of the original
      outbreak, since a less severe disease was recorded.

PMID- 12061641
TI  - Marek's disease in turkeys. II. Characterization of the viral glycoprotein B gene
      and antigen of a turkey strain of Marek's disease virus.
AB  - Marek's disease virus (MDV) causes immunosuppression and tumors in chickens. As
      sporadic cases of Marek's disease (MD) were recorded in turkeys, the antigenic
      and genomic characteristics of the MDV glycoprotein B (gB) gene and antigen of
      turkeys were compared to the chicken MDV gB. The whole chicken and turkey gB
      genes were sequenced and found identical. By immunoblotting of infected-cell
      culture lysates using chicken convalescent and gB monoclonal antibodies, the
      antigenic epitopes of the chicken and turkey viruses were found to differ. The
      turkey MDV had a unique epitope, compared to the chicken MDV and compared with
      our previous findings. While the chicken MDV had two epitope types, heat-labile
      but dithiothreitol (DTT)-stable and heat-stable but DTT-labile, the turkey MDV gB
      epitope is both heat and DTT-labile.

PMID- 12061642
TI  - Development of a competitive enzyme-linked immunosorbent assay for detection of
      turkey coronavirus antibodies.
AB  - A competitive enzyme-linked immunosorbent assay (cELISA) was developed for
      detection of turkey coronavirus (TCV) antibodies. The cELISA utilized a
      recombinant baculovirus (Autographa californica nuclear polyhedrosis virus)
      expressed TCV nucleocapsid (N) protein and biotin-labeled TCV N protein-specific
      monoclonal antibody. Sensitivity and specificity of the cELISA for detection of
      TCV antibodies were determined by comparison with the indirect fluorescent
      antibody test (IFAT) with 1269 reference, experimentally derived, and field
      origin sera. Sera with discordant cELISA and IFAT results were further evaluated
      by western immunoblot analyses. The cELISA detected antibodies specific for TCV
      and infectious bronchitis virus, a closely related coronavirus, but did not
      detect antibodies specific for other avian viruses. A high degree of concordance
      was observed between the cELISA and IFAT; sensitivity and specificity of the
      cELISA relative to IFAT were 92.9% and 96.2%, respectively. Western immunoblot
      analyses provided additional evidence of cELISA specificity. The findings
      indicate that the cELISA is a rapid, sensitive, and specific serologic test for
      detection of TCV antibodies in turkeys.

PMID- 12061643
TI  - Location of increased serum survival gene and selected virulence traits on a
      conjugative R plasmid in an avian Escherichia coli isolate.
AB  - Avian colibacillosis is a costly disease for the poultry industry. The mechanisms
      of virulence employed by the etiologic agent of this disease remain ill defined.
      However, accumulated evidence suggests that complement resistance and the
      presence of the increased serum survival gene (iss) in an avian Escherichia coli
      isolate may be indicative of its ability to cause disease. This association of
      iss with the E. coli implicated in avian disease may mean that iss and/or,
      perhaps, the genes associated with it are important contributors to avian E. coli
      virulence. For this reason, we have begun a search for iss's location in the
      bacterial genome. Thus far, iss in an avian E coli isolate has been localized to
      a conjugative R plasmid and estimated to be about 100 kilobase (kb) in size,
      encoding resistance to tetracycline and ampicillin. Hybridization studies have
      revealed that this plasmid contains sequences with homology to tsh, a gene
      associated with virulence of avian E coli; intI 1, a gene encoding the integrase
      of Class 1 integrons; and certain genes of the aerobactin- and CoIV-encoding
      operons. Sequences homologous to merA, a gene of the mercury resistance operon,
      were not identified on this R plasmid. This plasmid, when transferred into an
      avirulent, recipient strain by conjugation, enhanced the transconjugant's
      resistance to complement but not its virulence, in spite of the plasmid's
      possession of several putative virulence genes and traits. Such results may
      reflect the multifactorial nature of virulence, the degree of the recipient's
      impairment for virulence, or an inability of the embryo assay used here to detect
      this plasmid's contribution to virulence. Additionally, this plasmid contains
      genes encoding antimicrobial resistances, which may provide a selective advantage
      to virulent E. coli in the production environment. Further study will be needed
      to determine whether this plasmid is widespread among virulent E. coli and to
      ascertain the implications that this link between virulence and antimicrobial
      resistance genes may have for poultry management.

PMID- 12061644
TI  - Reduced efficacy of hemorrhagic enteritis virus vaccine in turkeys exposed to
      avian pneumovirus.
AB  - Avian pneumovirus (APV) is an immunosuppressive respiratory pathogen of turkeys.
      We examined the effect of APV infection on the vaccine efficacy of hemorrhagic
      enteritis virus (HEV) vaccines. APV was inoculated in 2-wk-old turkeys. Two or
      four days later, an attenuated HEV vaccine (HEVp30) or marble spleen disease
      virus (MSDV) vaccine were administered. Virulent HEV challenge was given 19 days
      after HEV vaccination. APV exposure compromised the ability of HEVp30 and MSDV to
      protect turkeys against virulent HEV. The protective index values were as
      follows: MSDV (100%) versus APV + MSDV (0%) (P < 0.05); HEVp30 (60%) versus APV +
      HEVp30 (30%) (P < 0.05) (Experiment I) and HEVp30 (56%) versus APV + HEVp30 (20%)
      (P < 0.05) (Experiment II). These data indicated that APV reduced the efficacy of
      HEV vaccines in turkeys.

PMID- 12061645
TI  - Prevalence of enteropathogenic Escherichia coli in naturally occurring cases of
      poult enteritis-mortality syndrome.
AB  - Enteropathogenic Escherichia coli (EPEC) previously were identified in poult
      enteritis-mortality syndrome (PEMS)-affected turkeys and associated as a cause of
      this disease. In the present study, the prevalence of EPEC in PEMS-affected
      turkeys was examined retrospectively with archived tissues and intestinal
      contents collected from 12 PEMS-affected turkey flocks in 1998. Formalin-fixed
      intestinal tissues were examined by light and electron microscopy for attaching
      and effacing (AE) lesions characteristic of EPEC, and frozen (-75 C) intestinal
      contents were examined for presence of EPEC. Escherichia coli isolates were
      characterized on the basis of epithelial cell attachment, fluorescent actin
      staining (FAS) test, and presence of E. coli attaching/effacing (EAE), shigalike
      toxin (SLT) type I, SLT II, and bundle-forming pilus (BFP) genes by polymerase
      chain reaction procedures. EPEC isolates were examined for pathogenicity and
      ability to induce AE lesions in experimentally inoculated young turkeys. AE
      lesions were identified by light microscopy in Giemsa-stained intestines from 7
      of 12 PEMS-affected turkey flocks. Lesions consisted of bacterial microcolonies
      attached to epithelial surfaces with epithelial degeneration at sites of
      attachment and inflammatory infiltration of the lamina propria. Electron
      microscopy confirmed the identity of AE lesions in six of seven flocks determined
      to have AE lesions by light microscopy. EPEC were identified in 4 of 12 flocks on
      the basis of the presence of EAE genes a nd absence of SLT I and SLT II genes;
      all isolates lacked BFP genes. EPEC isolates produced AE lesions and variable
      mortality in turkeys coinfected with turkey coronavirus. In total, EPEC were
      associated with 10 of 12 (83%) naturally occurring PEMS cases on the basis of
      identification of AE lesions and/or EPEC isolates. These findings provide
      additional evidence suggesting a possible role for EPEC in the pathogenesis of
      PEMS.

PMID- 12061646
TI  - A serotype-specific polymerase chain reaction for identification of Pasteurella
      multocida serotype 1.
AB  - A serotype-specific polymerase chain reaction (PCR) assay was developed for
      detection and identification of Pasteurella multocida serotype 1, the causative
      agent of avian cholera in wild waterfowl. Arbitrarily primed PCR was used to
      detect DNA fragments that distinguish serotype 1 from the other 15 serotypes of
      P. multocida (with the exception of serotype 14). Oligonucleotide primers were
      constructed from these sequences, and a PCR assay was optimized and evaluated.
      PCR reactions consistently resulted in amplification products with reference
      strains 1 and 14 and all other serotype 1 strains tested, with cell numbers as
      low as 2.3 cells/ml. No amplification products were produced with other P.
      multocida serotypes or any other bacterial species tested. To compare the
      sensitivity and further test the specificity of this PCR assay with traditional
      culturing and serotyping techniques, tissue samples from 84 Pekin ducks
      inoculated with field strains of P. multocida and 54 wild lesser snow geese
      collected during an avian cholera outbreak were provided by other investigators
      working on avian cholera. PCR was as sensitive (58/64) as routine isolation
      (52/64) in detecting and identifying P. multocida serotype 1 from the livers of
      inoculated Pekins that became sick or died from avian cholera. No product was
      amplified from tissues of 20 other Pekin ducks that received serotypes other than
      type 1 (serotype 3, 12 x 3, or 10) or 12 control birds. Of the 54 snow geese
      necropsied and tested for P. multocida, our PCR detected and identified the
      bacteria from 44 compared with 45 by direct isolation. The serotype-specific PCR
      we developed was much faster and less labor intensive than traditional culturing
      and serotyping procedures and could result in diagnosis of serotype 1
      pasteurellosis within 24 hr of specimen submission.

PMID- 12061647
TI  - The carry-over of Campylobacter isolates between sequential poultry flocks.
AB  - The carry-over of Campylobacter strains from one flock to a subsequent flock in
      the same broiler house has been studied using molecular epidemiological
      techniques. In all, 524 Campylobacter strains, isolated from two sequential
      broiler flocks from 60 broiler houses, were typed by restriction fragment
      polymorphism of the polymerase chain reaction (PCR) product of the flaA and flaB
      genes (fla typing). Selected strains were also typed using pulsed field gel
      electrophoresis (PFGE). By fla typing, 15 (21%) of the 60 houses with
      Campylobacter-positive sequential flocks had identical genotypes. In 10 (16%
      overall) of these houses the strains were also identical by PFGE. The difference
      in PFGE patterns in the strains from the three remaining houses may be indicative
      of genetic instability. Overall, these results suggest that carry-over from one
      flock to a subsequent flock in the same house is a relatively infrequent event
      and, therefore, that routine broiler house cleansing and/or disinfection is
      largely adequate to eliminate Campylobacter contamination. An alternative
      explanation of the low level carry-over is a persistent source or reservoir,
      external to the environment of the broiler houses.

PMID- 12061649
TI  - Heteroduplex mobility assay for detection of new avian influenza virus variants.
AB  - Highly pathogenic avian influenza (HPAI) in poultry causes high morbidity and
      mortality, and it is a List A disease of the Office International des Epizooties.
      An outbreak of HPAI in commercial poultry not only causes direct disease losses
      but often results in trade restrictions for the affected country. Because HPAI
      viruses can mutate from H5 and H7 low pathogenic avian influenza viruses, it is
      necessary to monitor and control even the low pathogenic form of the virus. We
      report a practical approach for screening large numbers of isolates that uses
      amplification by reverse transcriptase-polymerase chain reaction of a segment of
      the hemagglutinin (HA) gene (536-560 bp) of H7 avian influenza viruses followed
      by the heteroduplex mobility assay (HMA). The HMA test compares the amplified
      polymerase chain reaction product from unknown samples with reference isolates,
      which allows the identification of new variants. The HMA test results were
      compared with sequence analysis of the isolates used in the study. On the basis
      of the HMA, we could identify several new variant viruses present in the live
      bird markets in the northeastern United States. New strains gave a distinct
      pattern of bands in the gels in accordance with the different heteroduplexes
      formed when their HA region amplification products were incubated together with
      the same amplification product of a reference strain. These differences correlate
      with phylogenetic analysis from sequence data.

PMID- 12061648
TI  - Complement resistance, as determined by viable count and flow cytometric methods,
      and its association with the presence of iss and the virulence of avian
      Escherichia coli.
AB  - Previous work in our labs has shown that avian Escherichia coli virulence is
      correlated with resistance to complement. Also, our studies have revealed that
      the presence of the increased serum survival gene (iss), known to contribute to
      the complement resistance and virulence of mammalian E. coli, may predict the
      virulent nature of an avian E. coli isolate. This relationship warrants further
      research, but further clarification of the relationship among virulence,
      complement resistance, and iss sequences requires use of complement
      susceptibility assays. Such assays, unfortunately, are labor-intensive,
      expensive, and difficult to perform. In the present study, the results of two
      complement susceptibility assays for 20 E. coli isolates, 10 incriminated in
      avian colibacillosis and 10 from the intestinal tracts of apparently healthy
      birds, were compared in an attempt to determine if flow cytometric analysis was a
      reasonable alternative to a viable count assay. In addition, the virulence of
      these isolates for chick embryos was determined, and each isolate was examined
      for the presence of iss using amplification techniques. The flow cytometric
      method was found to be repeatable for most isolates, and its results showed
      moderate agreement with those obtained through viable counts. All intestinal
      isolates of healthy birds proved avirulent using the embryo lethality assay;
      however, not all isolates from sick birds were demonstrated to be virulent.
      Possible explanations of these results include that the methods originally used
      to isolate these organisms failed to detect the illness-inciting strains or that
      the virulence of these strains had declined following initial isolation.
      Additionally, we must consider the possibility that the embryo lethality assay of
      virulence used here might not be sensitive enough to detect differences between
      these two groups of isolates. Also, it should be noted that virulence assays,
      such as the one used here, fail to account for predisposing host or environmental
      conditions, enabling a less virulent isolate to cause disease under natural
      conditions. Interestingly, the complement resistance of a strain was
      significantly associated with its lethality in embryos, and iss-containing
      isolates were significantly more likely than those lacking iss to be classified
      as complement-resistant and virulent. Such results, at least for this group of
      avian E. coli, suggest that there is a compelling but imperfect relationship
      among complement resistance, virulence, and the presence of iss. These results
      also suggest that the flow cytometric assay may be a reasonable alternative to
      the viable count method of determining complement resistance.

PMID- 12061650
TI  - Effect of drinking water chlorination on Campylobacter spp. colonization of
      broilers.
AB  - The main source for Campylobacter spp. transmission from the environment to
      broiler chickens is still unclear. One implicated reservoir for the organism has
      been untreated broiler drinking water. This study was conducted with broilers
      first using experimental conditions (isolation units) and second under commercial
      conditions. We compared the rate of intestinal colonization in chickens provided
      2 to 5 parts per million (ppm) chlorinated drinking water in relation to the
      frequency of colonization in chickens given unsupplemented drinking water. No
      significant difference (P > 0.05) was detected in isolation frequency or level of
      Campylobacter spp. colonization in birds provided chlorinated drinking water and
      control birds provided water without supplemental chlorine. In the isolation unit
      experiments, 86.3% (69/80) of the control and 85.0% (68/80) of the treated birds
      were colonized at levels corresponding to an average of 10(5.2) and 10(5.1) log
      colony-forming units (cfu) Campylobacter spp./g of cecal contents, respectively.
      Additionally, two sets of paired 20,000 bird broiler houses, with and without
      chlorination (2-5 ppm chlorine), were monitored in a commercial field trial.
      Effectiveness of chlorination was judged by prevalence of Campylobacter spp. in
      fecal droppings (960 samples) taken from the flocks in treated and control
      houses. Birds from the control houses were 35.5% (175/493) Campylobacter spp.
      positive, while 45.8% (214/467) of the samples from the houses having chlorinated
      drinking water yielded the organism. Chlorination of flock drinking water at the
      levels tested in this study was not effective in decreasing colonization by
      Campylobacter spp. under commercial production practices presently used in the
      United States.

PMID- 12061652
TI  - Experimental infection of turkeys with avian pneumovirus and either Newcastle
      disease virus or Escherichia coli.
AB  - Avian pneumoviruses (APVs) are RNA viruses responsible for upper respiratory
      disease in poultry. Experimental infections are typically less severe than those
      observed in field cases. Previous studies with APV and Escherichia coli suggest
      this discrepancy is due to secondary agents. Field observations indicate APV
      infections are more severe with concurrent infection by Newcastle disease virus
      (NDV). In the current study, we examined the role of lentogenic NDV in the APV
      disease process. Two-week-old commercial turkey poults were infected with the
      Colorado strain of APV. Three days later, these poults received an additional
      inoculation of either NDV or E. coli. Dual infection of APV with either NDV or E.
      coli resulted in increased morbidity rates, with poults receiving APV/NDV having
      the highest morbidity rates and displaying lesions of swollen infraorbital
      sinuses. These lesions were not present in the single APV, NDV, or E coli groups.
      These results demonstrate that coinfection with APV and NDV can result in
      clinical signs and lesions similar to those in field outbreaks of APV.

PMID- 12061651
TI  - Detection of antibodies to Mycoplasma gallisepticum vaccine ts-11 by an
      autologous pMGA enzyme-linked immunosorbent assay.
AB  - Mycoplasma gallisepticum is a poultry pathogen that causes respiratory disease
      and loss of egg production worldwide. A live attenuated vaccine, ts-11, has been
      used for control of M. gallisepticum in several countries. The rapid serum
      agglutination test is usually used as an indicator of flock response to
      vaccination; however, in some flocks, the detected response may be weak or
      absent. With the use of specific monoclonal antibodies against M. gallisepticum
      strain S6 pMGA in immunoaffinity purification, the major membrane antigen of ts
      11 was purified. An indirect enzyme-linked immunosorbent assay (ELISA) was
      developed with the purified antigen, and its potential for detection of
      antibodies induced after ts-11 vaccination was compared with an indirect ELISA
      with M. gallisepticum strain S6 pMGA. In the presence of high levels of ts-11
      induced antibodies, both antigens detected similar numbers of positive sera.
      However, when lower levels of antibodies were present, ts-11 pMGA showed a higher
      sensitivity than S6 pMGA. Further examination of ts-11 pMGA with Mycoplasma
      synoviae-infected chicken sera revealed that ts-11 pMGA is specific for M.
      gallisepticum antibodies. With a panel of sera from ts-11-vaccinated or non-ts-11
      vaccinated field chickens, the ts-11 pMGA ELISA was found to be more sensitive
      than the commercial rapid serum agglutination test in detecting antibodies to ts
      11 vaccine. The results from this study suggest that the major membrane antigen
      of M. gallisepticum may have slightly different antigenic profiles in different
      strains, thereby necessitating the use of autologous antigens in serodiagnostic
      assays to increase sensitivity of the tests for mycoplasma antibodies. Thus, the
      low level of antibody response after ts-11 vaccination is, at least partially,
      due to the low ability of the current diagnostic antigens to bind ts-11
      antibodies.

PMID- 12061653
TI  - The effects of 6/85 live Mycoplasma gallisepticum vaccine in commercial layer
      hens over a 43-week laying cycle on egg production, selected egg quality
      parameters, and egg size distribution when challenged before beginning of lay.
AB  - In each of two trials, 80 commercial leghorn-type pullets were separated into two
      treatments with four replicates of 10 chickens in each treatment. Forty pullets
      were designated as controls and received no inoculation, whereas the remaining 40
      pullets received the 6/85 vaccine strain of Mycoplasma gallisepticum (MG) at 10
      wk of age. Hen-day egg production, egg weight, eggshell strength, Haugh unit
      score, pimpling incidence, and blood/meat spot incidence were monitored and
      recorded weekly in each trial through an entire laying cycle of 43 wk. Further,
      eggs from all treatments were collected daily, Monday-Thursday, and individually
      weighed. No significant difference was observed between the treatments for 43-wk
      means for hen-day egg production, for any of the monitored egg or eggshell
      quality parameters, or for the number of extra large, large, medium, small, pee
      wee, or undergrade egg sizes. A significant (P < or = 0.05) difference was
      observed for the number of jumbo-sized eggs between the two treatments. Results
      of this study suggest that vaccination of commercial layer chickens at 10 wk of
      age with 6/85 strain MG does not detrimentally impact egg production, egg size
      distribution, or ovary/oviduct function as evidenced by selected egg parameters
      monitored in this study.

PMID- 12061654
TI  - Genetic and antigenic characterization of a poxvirus isolate from ostriches.
AB  - Avian poxvirus was isolated from nodules on the heads and conjunctiva of two 3-to
      4-wk-old ostrich chicks. The ostriches from which poxvirus was isolated had been
      placed on premises where turkeys that had shown evidence of poxvirus infection
      had been raised earlier. Microscopically, the nodules from the ostriches were
      composed of proliferating and hypertrophic epithelial cells that formed large
      fronds. Most of the hypertrophic epithelial cells contained large eosinophilic
      intracytoplasmic inclusion bodies characteristic of poxvirus. Characterization of
      the avian poxvirus isolated from the cutaneous lesions in ostriches was based on
      western blotting of virus antigen, restriction fragment length polymorphism of
      genomic DNA, pathogenesis, and cross-protection studies in chickens. Antigenic
      and genetic studies did not reveal any significant difference between the
      poxvirus isolated from ostriches (PVO) and fowl poxvirus (FPV). Further,
      susceptible chickens immunized with the PVO were protected when challenged with a
      virulent strain of FPV. Thus, the poxvirus isolated from ostriches had similar
      antigenic, genetic, and biological properties to FPV.

PMID- 12061655
TI  - Genetic and antigenic diversity in avian infectious bronchitis virus isolates of
      the 1940s.
AB  - In order to verify a commonly held assumption that only Massachusetts (Mass)
      serotype of infectious bronchitis virus (IBV) was prevalent in the United States
      between the 1930s (when IBV was first isolated) and the 1950s (when the use of
      commercial IBV vaccines began), we examined 40 IBV field isolates from the 1940s.
      Thirty-eight of those isolates were recognized as Mass serotype viruses based on
      their reactivity to Mass-specific monoclonal antibody (Mab) and neutralization by
      Mass-specific chicken serum. The remaining two isolates, N-M24 and N-M39, that
      did not react with Mass-specific Mab, resisted neutralization by Mass-specific
      chicken serum, and were neutralized only by homologous chicken antibody were
      identified as non-Mass IBV. When the first 900 nucleotides (nt) from the 5'-end
      of the spike (S1) glycoprotein gene and their deduced amino acid (aa) sequences
      were compared, the two non-Mass isolates differed from each other by 24% and 28%,
      respectively. In a similar comparison, the non-Mass viruses N-M24 and N-M39
      differed from M28, a Mass-type isolate from the 1940s, by 21% and 22% (nt) and
      28% and 27% (aa), respectively. These data indicate that antigenic and genetic
      diversity among IBV isolates existed even in the 1940s. Interestingly, when the N
      terminal region of the S1 of M28 was compared to that of M41, a prototype Mass
      virus that has undergone countless number of in vivo and in vitro host passages,
      the two viruses differed by only 2% (nt) and 4% (aa). This finding suggests that
      frequent genetic changes are not inherent in all IBV genomes.

PMID- 12061656
TI  - Investigation of the presence of Ornithobacterium rhinotracheale in chickens in
      Turkey and determination of the seroprevalance of the infection using the enzyme
      linked immunosorbent assay.
AB  - In this study, the presence of Ornithobacterium rhinotracheale infection in the
      avian population in the Marmara and the Western Black Sea region was
      investigated. Trachea samples were randomly obtained from 96 chickens sent to
      slaughterhouses. The seroprevalance of the infection was determined in 384 blood
      sera. Ninety-six of these 384 samples belonged to animals from which trachea
      samples were obtained. Eleven (11.46%) O. rhinotracheale were isolated in 96
      trachea samples taken from 10 different flocks brought to the slaughterhouse.
      Serotype A was the predominant serotype among the 11 isolates of O.
      rhinotracheale. One isolate could not be serotyped. O. rhinotracheale antibodies
      were detected in 251 (64.4%) of the 384 sera, while 55 (14.3%) and 78 (20.3%)
      were suspected and negative, respectively.

PMID- 12061657
TI  - Isolation of an unidentified, nonfermentative, gram-negative bacterium from
      turkeys and chickens: 38 cases (1995-2001).
AB  - Thirty-eight cases were identified in which a nonfermentative, gram-negative, rod
      shaped bacterium was isolated from the respiratory system of turkeys and
      chickens. Cases were submitted from various parts of the country. Preliminary
      assessment of phenotypic characteristics indicated this bacterium was different
      from common pathogenic or opportunistic bacteria isolated from the avian
      respiratory tract. Most cases reported a history of respiratory distress and/or
      increased flock mortality. Lesions seen in infected birds included tracheitis and
      pneumonia, which correlate with the sites of isolation. Sixty-one percent of the
      isolations were made from the trachea and 25% from the lung. Age of infected
      birds ranged from 35 to 315 days in turkeys and 53 days to 3 yr in chickens. In
      most instances (90%), other bacteria were also isolated from affected sites. The
      significance of this organism in respiratory disease in birds is unknown.

PMID- 12061658
TI  - Seroprevalence of antibodies specific for gram-negative core antigens in chickens
      on the basis of an Escherichia coli J5 enzyme-linked immunosorbent assay.
AB  - Antibodies directed toward gram-negative core antigens (GNCAs) have been
      demonstrated in many mammalian species but to date are unexamined in any avian
      species. An enzyme-linked immunosorbent assay with phenol-killed whole cell
      Escherichia coli J5 was used to assess the presence of serum antibodies directed
      toward GNCAs in chickens. The first experiment consisted of collecting blood
      samples from randomly selected hens at egg laying ranches in northern California.
      The ages ranged from several days of age to 77 wk of age. Birds were classified
      into age groups (hatchling [1 day-4 wk], pullet [4-18 wk], pullet cycle [18-60
      wk], and postmolt [>60 wk]) and husbandry style for titer comparison. The
      geometric mean titer (GMT) for all adult hens regardless of age was 2147. The
      geometric mean titers were 220, 5691, 2304, and 1776 for hatchlings, pullets,
      pullet cycle hens, and postmolt hens, respectively. The age group titer trends
      were similar to those of humans rather than those of farm animals in that the
      highest titers occurred during "adolescence" (pullets) and titers decreased
      slightly with maturity. The GMTs were 2870 for hens housed intensively and 1872
      for those housed extensively. The second experiment looked at the progression of
      GNCA titers within individual birds over a 1-yr period. Individual titers
      increased slightly throughout the study time of the second experiment.

PMID- 12061659
TI  - Clinical epidemiologic and experimental evidence for the transmission of
      Newcastle disease virus through eggs.
AB  - Sporadic outbreaks of Newcastle disease (ND) occurred in Taiwan during 1998-2000.
      In some cases, the disease occurred in broilers less than 2 wk old that
      originated in a broiler breeder farm, so spread of the ND virus (NDV) from the
      infected breeder farm to broiler ranches was suspected. The purpose of the
      present study was to examine the possibility of the transmission of NDV through
      eggs. Both clinical and experimental evidence were used to prove that this is
      possible. From epidemiological investigation, the possibility of transmission
      through eggs was suggested in two separate ND cases from a breeder farm and its
      progeny because two identical NDVs were isolated from both cases. In order to
      clarify the possibility of the transmission through eggs, one mean egg lethal
      dose (ELD50) of NDV was inoculated into the allantoic cavity of 155 9-to-11-day
      old specific-pathogen-free (SPF) chicken embryos. Seventy-one hatching chicks
      from the inoculated embryos were raised for 14 days. The cloacal swabs from those
      chicks at the ages of 1, 4, and 7 days and the tissues after necropsy at the ages
      of 14 days were taken for virus isolation. The same NDV was reisolated from three
      hatching chicks. This experiment confirms that a few chicken embryos infected in
      ovo with a low titer of NDV can hatch and contain NDV after hatching, which
      results in NDV spreading through eggs.

PMID- 12061660
TI  - Antigenic relationship of turkey coronavirus isolates from different geographic
      locations in the United States.
AB  - The purpose of the present study was to examine the antigenicity of turkey
      coronavirus (TCV) isolates from various geographic areas with antibodies to
      different viruses. Seventeen isolates of TCV were recovered from intestinal
      samples submitted to Animal Disease Diagnostic Laboratory, Purdue University,
      from turkey farms located in different geographic areas. The prototype TCV
      Minnesota isolate (TCV-ATCC) was obtained from the American Type Culture
      Collection. Intestinal sections were prepared from turkey embryos infected with
      different TCV isolates and reacted with polyclonal or monoclonal antibodies to
      TCV, infectious bronchitis virus (IBV), bovine coronavirus (BCV), transmissible
      gastroenteritis virus (TGEV), reovirus, rotavirus, adenovirus, or enterovirus in
      immunofluorescent antibody staining. All 18 TCV isolates have the same antigenic
      reactivity pattern with the same panel of antibodies. Positive reactivity was
      seen with polyclonal antibodies to the TCV Indiana isolate, the TCV Virginia
      isolate, TCV-ATCC, and the IBV Massachusetts strain as well as monoclonal
      antibodies to the TCV North Carolina isolate or the membrane protein of IBV.
      Antibodies to BCV or TGEV were not reactive with any of the TCV isolates.
      Reactivity of antibodies to unrelated virus, rotavirus, reovirus, adenovirus, or
      enterovirus with different TCV isolates was all negative, except positive
      response was seen between enterovirus antibody and a TCV western North Carolina
      isolate, suggesting coinfection of turkeys with TCV and enterovirus in that
      particular case. The results indicated that the TCV isolates from these
      geographic locations in the U.S. shared close antigenicity and were antigenically
      related to IBV.

PMID- 12061661
TI  - Cecal colonization of chicks by porcine strains of Campylobacter coli.
AB  - Ten genotypically distinct strains of Campylobacter coli were isolated from a
      swine production facility. These porcine isolates were then orally inoculated
      into day-of-hatch leghorn chicks and were excellent colonizers of the chick
      cecum. Campylobacter coli recovered from inoculated chickens were genotypically
      identical to the challenge strain. The absence of host specificity suggests a
      possible movement of strains among swine, field animals and birds, and poultry
      houses.

PMID- 12061662
TI  - Isolation and characterization of a reovirus from common eiders (Somateria
      mollissima) from Finland.
AB  - Samples of brain, intestine, liver, lung, spleen, and bursa of Fabricius were
      collected from five common eider (Somateria mollissima) duckling carcasses during
      a die-off in the western Gulf of Finland (59 degrees 50'N, 23 degrees 15'E) in
      June 1996. No viral activity was observed in specific-pathogen-free chicken
      embryos inoculated with tissue suspensions, but samples of bursa of Fabricius
      from three birds were positive when inoculated into Muscovy duck (Cairina
      moschata) embryo fibroblasts. The isolates were characterized as nonenveloped RNA
      viruses and possessed several characteristics of the genus Orthoreovirus. Virus
      particles were icosahedral with a mean diameter of 72 nm and were stable at pH
      3.0; their genome was separated into 10 segments by polyacrylamide gel
      electrophoresis. Mallard (Anas platyrhynchos) ducklings experimentally infected
      with the eider reovirus showed elevated serum activities of aspartate
      aminotransferase, creatine kinase, and lactate dehydrogenase enzymes and focal
      hemorrhages in the liver, spleen, and bursa of Fabricius. During 1997-99, the
      prevalence of neutralizing antibodies to the isolated virus ranged from 0 to 86%
      in 302 serum samples collected from incubating eider hens at three nesting areas
      along coastal Finland. The highest seroprevalence was found in Hanko in 1999,
      just weeks before reports of an uninvestigated mortality event resulting in the
      death of an estimated 98% of ducklings at that location. These findings raise the
      question of potential involvement of the virus in poor duckling survival and
      eider population declines observed in several breeding areas along coastal
      Finland since the mid-1980s.

PMID- 12061663
TI  - Reovirus infection in psittacine birds (Psittacus erithacus): morphologic and
      immunohistochemical study.
AB  - In this paper we report on an outbreak of reovirus, herpesvirus (Pacheco
      disease), and/or mycosis infection (Aspergillus spp. and Zygomyces spp.)
      affecting a batch of young African grey parrots (Psittacus erithacus), with 80%
      morbidity and 30% mortality. Study material was taken from five birds (four dead
      and one euthanatized) with a range of clinical symptoms (depression, diarrhea,
      respiratory symptoms). Diagnosis was confirmed by immunohistochemical detection
      of avian reovirus, electron microscopy, and virus isolation. Viral antigen of
      reovirus was detected mainly in large mononuclear cells in the bursa of Fabricius
      and the spleen, pancreas epithelial cells, and circulating cells; lymphoid organs
      displayed the largest number of immunopositive cells and severe lymphocyte
      depletion. Bacteriologic study was negative. Reovirus infection was common in all
      birds studied, whereas Pacheco disease and mycosis were found in only some,
      suggesting that reovirus could be the initial cause triggering the outbreak and
      facilitating infection by other agents and their swift spread through the batch.

PMID- 12061665
TI  - A case of aspergillosis in a broiler breeder flock.
AB  - A case of aspergillosis in a broiler breeder flock having respiratory and nervous
      system problems caused by Aspergillus fumigatus and Aspergillus niger is
      documented. Dyspnea, hyperpnea, blindness, torticollis, lack of equilibrium, and
      stunting were observed clinically. On postmortem examination of the affected
      birds, white to yellow caseous nodules were observed on lungs, thoracic air sacs,
      eyes, and cerebellum. Histopathologic examination of lungs and cerebellum
      revealed classic granulomatous inflammation and cerebellar lesions, necrotic
      meningoencephalitis, respectively. No lesions were noted in the cerebrum
      histopathologically. Aspergillus hyphae were observed in stained sections
      prepared from lesioned organs. Fungal spores and branched septate hyphae were
      observed in direct microscopy. Aspergillus fumigatus and A. niger were isolated
      from the inoculations prepared from the suspensions of organs showing lesions.

PMID- 12061664
TI  - Thoracic teratoma in a white Pekin duck (Anas platyrhinchos domesticus).
AB  - Teratomas are infrequent tumors in domestic fowl and have been rarely reported in
      ducks. It appears that the only case of mediastinal teratoma in a Pekin duck was
      observed by Alezais and Cotte in 1908. A lobulated, firm mass occupied the thorax
      of a 7-mo-old male white Pekin duck (Anas platyrhinchos domesticus). The tumor
      was composed of squamous epithelium, feather follicles, glandular epithelium,
      bone and cartilage, and thymus and was classified as tridermic, thoracic
      teratoma.

PMID- 12061666
TI  - Mycobacterium tuberculosis infection in a canary (Serinus canana L.) and a blue
      fronted Amazon parrot (Amazona amazona aestiva).
AB  - I report two cases of mycobacteriosis in pet birds due to Mycobacterium
      tuberculosis and discuss the zoonotic implications. The canary with a tuberculous
      knot in the lung is the first description of M. tuberculosis in a nonpsittacine
      bird species.

PMID- 12061667
TI  - Increased mortality in turkeys selected for increased body weight following
      vaccination with a live Newcastle disease virus vaccine.
AB  - Candidate male and female breeders from nine genetic lines of turkeys that were
      reared intermingled, with the sexes housed in different buildings on the same
      farm, were vaccinated with a live Newcastle disease virus vaccine (B1 type,
      LaSota) just prior to the commencement of egg production. In 1999, an average
      mortality for all lines of 5.8% occurred during the 10 days immediately following
      vaccination and the level of mortality varied among lines. Mortality was, in
      general, greater in large-bodied lines than in small-bodied lines. Affected birds
      exhibited gross multiple areas of focal necrosis in the liver and spleen and
      congestion of the heart and lungs. The percentage mortality occurring following
      similar vaccination in 2000 averaged 2.6 for the 10 days following vaccination
      and mortality was greater (P < or = 0.05) in one line (F line) than the other
      genetic groups and higher in females than in males. Mortality in the F line,
      selected for increased body weight and known to be susceptible to various
      diseases, averaged 15.1% for both years. Attempts failed in both years to isolate
      Pasteurella multocida or other bacteria. There was a positive correlation between
      increased body weight and increased mortality following vaccination with the live
      LaSota vaccine.

PMID- 12061668
TI  - Diagnosis by polymerase chain reaction of Erysipelas septicemia in a flock of
      ring-necked pheasants.
AB  - A flock of 810 pheasants experienced 6.2% mortality over 6 days. Affected birds
      were weak and lethargic for up to 24 hr before death. Examined birds were thin,
      and gross lesions consisted of thick opaque crops and cecal cores.
      Histologically, there was capillariasis of the crop and multifocal ulcerative
      typhlitis with Heterakis spp. infection, and numerous systemic intravascular
      monocytes were filled with clusters of blue rod-shaped organisms. The organisms
      were gram-positive bacilli by Brown and Brenn staining and ultrastructural
      analysis. Liver bacterial cultures were negative for pathogenic bacteria.
      Erysipelas septicemia was diagnosed by an Erysipelothrix species-specific
      polymerase chain reaction method with the substrate DNA isolated from formalin
      fixed, paraffin-embedded liver.

PMID- 12061669
TI  - Audit of aminoglycosides usage.
AB  - OBJECTIVE: This study was aimed to evaluate the usage patterns of aminoglycosides
      in pediatric patients for their appropriateness. METHODS: A retrospective review
      was conducted over a period of six months at J.S.S. Hospital, Mysore. Patients
      who received parenteral aminoglycosides and below the age of 12 years were
      included in this study. RESULTS: A total of 197 pediatric patients were evaluated
      for the appropriateness and was found to be 72%, 86%, 85%, 43% & 53% for
      indication, dose, duration, safety and cost effectiveness respectively. Majority
      of the patients were treated with gentamicin (53%). The most frequent indication
      was respiratory tract infections (50%). CONCLUSION: Effort was made to encourage
      judicious and quality use of aminoglycosides among the pediatricians of J.S.S.
      Hospital to ensure better patient care by implementation of the aminoglycosides
      guidelines.

PMID- 12061670
TI  - Does early erythropoietin therapy decrease transfusions in anemia of prematurity?
AB  - OBJECTIVE: To investigate the effect of early erythropoietin treatment on
      induction of erythropoiesis and the need for transfusion in Very Low Birth Weight
      (VLBW) infants with acute neonatal problems. METHODS: The study group consisted
      of 14 VLBW prematures with gestational ages less than 32 weeks who were given
      subcutaneous erythropoietin (600 U/kg per week) and oral iron (3 mg/kg per day)
      during the first 7-8 weeks of their life, while 13 other VLBW prematures that
      were given placebo constituted the control group. Weekly hematocrit, (Hct)
      reticulocyte (Ret) values and the volume of blood drawn and transfused were
      recorded in the both groups. RESULTS: The groups were comparable regarding with
      birth weights and gestational ages. The volume of the blood drawn (76.8 +/- 42.5
      and 37.0 +/- 15.2) was higher and the volume of the transfusions (51.84 +/- 49.30
      and 68.84 +/- 41.2) was lower in the study group but the differences between the
      groups were not significant (p>0.05). The hematocrit, the reticulocyte and the
      ferritin values were similar in both the groups at the end of the therapy.
      CONCLUSION: Under the neonatal intensive care circumstances of developing
      countries where blood volumes needed for laboratory analysis are still very high,
      phlebotomy losses can not be avoided. Thus early erythropoietin and iron therapy
      at these doses are not effective in decreasing the need for transfusion and
      induction of endogenous erythropoiesis.

PMID- 12061671
TI  - Rotavirus and enteric pathogens in infantile diarrhoea in Manipal, South India.
AB  - The etiology of Rotavirus in acute diarrhoeal illness in children 0-5 years of
      age, admitted to the pediatric wards of Kasturba Medical College Hospital,
      Manipal was studied over a period of 5 years. Rotavirus in the faeces detected by
      Latex agglutination test accounted for 19.56% of the diarrhoea with maximum
      incidence (65%) in the 7-12 months of age group. Bacterial aetiological agents
      continued to play a significant role (69.6%) in diarrhoeal diseases.
      Enteroaggregative E. coli was common in the age group between 25-36 months,
      Shigellosis in 37-60 months and Salmonella typhimurium enteritis in 7-12 months
      of age. The other pathogens isolated were vibrio cholerae (4.98%), species of
      aeromonas (15.92%), along with cryptosporidium (6.47%) and candida albicans
      (3.98%). In a control group consisting of 100 children without history of
      diarrhoea, 2 were positive for rotavirus, 3 for cryptosporidium and 12 for
      Escherichia coli.

PMID- 12061672
TI  - Why do some boys run away from home?
AB  - OBJECTIVE: Insufficient research has been done to look for the factors compelling
      children to make street, their home. The study was conducted at a Child
      Observation Home to which street children from all over Delhi, are brought.
      METHODS: Each boy admitted during the specified 6 months period was interviewed.
      Chi2 and Fisher's test were applied. A total of 400 boys were studied, 9.8% of
      these had not run away from their homes and 89.2% were "Runaways". These two
      groups were compared and following factors were found associated with the
      "Runaway" group. RESULT: Majority (55%) had left home between 10-12 year of age.
      They were more from "Joint" families. A higher percentage had literate fathers. A
      higher percentage had no parent earning and a higher proportion of "Not Runaways"
      had only the mother earning. Presence of a step parent, guardian other than the
      parents and intra-familial physical abuse were found associated with "Runaway"
      group. CONCLUSION: The most common reason for running away was; beating by
      parents/relatives, followed by a desire for economic independence (28.5%). Other
      reasons were maltreatment by step parent/s, being both parents dead argument with
      parent etc. The factors emerging can be useful for identifying high-risk families
      with children in pre adolescent age and hence for prevention and rehabilitation.

PMID- 12061673
TI  - Enteral feeding of low birth weight infants.
AB  - There is sufficient evidence at present to support early enteral feeding of low
      birth weight (LBW) neonates, including those who are sick or very preterm (< 30
      weeks). Trophic feeding with human milk initiated within 48 hours of birth at 10
      15 ml/kg/day improves later tolerance to graded increment of enteral feeding
      volumes without increased risk of necrotizing enterocolitis. Trophic feeding
      supports increments of feeding volumes by 30 ml/kg/day by intermittent gavage
      feeding. Non-nutritive sucking and spoon-feeding aid earlier transition to
      exclusive breast-feeding. Human milk promotes adequate growth of most preterm
      neonates, though many need multivitamin and mineral supplementation. The role of
      human milk fortifiers to promote growth appears controversial.

PMID- 12061675
TI  - Nutrition support in a surgical patient.
AB  - Nutrition has very important role to play during health and disease state in
      human beings. Neonates and younger children are more prone to develop nutritional
      deficiencies. They have very critical reserves and are rapidly growing. Any
      surgical insult leads to multiple nutritional problems. Careful planning of
      nutritional management in a surgical patient is mandatory. Nutritional support
      should start from the day when the child develops the surgical condition to
      withstand stress of disease and surgical procedure. In the postoperative period
      nutritional support should start as early as possible. Start with small amount
      and build up gradually till the normal enteral nutrition (EN) is tolerated. When
      EN is not tolerated parenteral nutrition (PN) should be considered. Parenteral
      nutrition on short term basis is very important to tide over the crisis due to
      postoperative complications. Parenteral nutrition on long term basis is required
      in short bowel syndrome resulting from resection of large part of the gut. During
      PN, enteral nutrition should be continued in small amounts in order to maintain
      the integrity of mucosal lining of the gut. Enteral nutrition is more
      physiological and can provide adequate amount of immunonutrients, minerals and
      vitamins.

PMID- 12061674
TI  - Nutritional support in the critically ill child.
AB  - The nutritional management of a critically ill child is not a glamorous subject
      and seldom receives the attention that it merits despite increasing evidence that
      appropriate goal-oriented nutritional support is associated with improved
      outcome. Current nutritional management is based on rapidly emerging knowledge on
      the very special nutritional requirements related to the "vastly different
      metabolic and physiologic characteristics of the hypermetabolic and stressed"
      critically ill child. There has been significant changes in traditional practice
      particularly in the area of calorie delivery, amount of macronutrients and route
      of nutrient delivery in the critically ill child. The critically ill child
      presents with "greatly disordered nutrient metabolism" and successful nutritional
      support involves an initial "hypocaloric regime" with a precise mix of
      carbohydrates, proteins and lipids which need periodic review as the child
      improves. The therapeutic benefits of minimal enteral feeding (MEF) have been
      clearly established--MEF being associated with diminished morbidity, infection
      rates as well as reduced ICU and hospital stays. Immune enhancement has also been
      shown to be of some benefit in the critically ill but the subject needs further
      study.

PMID- 12061676
TI  - Immunonutrition.
AB  - Nutrition and immunology are interrelated. Several nutrients like arginine,
      glutamine, omega-3-fatty acids and nucleotides enhance cellular immunity,
      modulate tumor cell metabolism and improve clinical outcome in stress situations.
      Glutamine supplementation has been shown to decrease incidence of sepsis and to
      reduce length of hospital stay in bone marrow transplant patients, low birth
      weight infants, surgical and multiple trauma patients. Studies with arginine have
      shown a reduction in infectious complications and lower mortality, however a
      better understanding of the biology of arginine is needed. Omega-3-fatty acid
      supplimentation as in fish oil stimulates the immune system. The beneficial
      effects of immunonutrition in surgical patients has been demonstrated in several
      studies. It significantly reduces infectious complications and length of hospital
      stay. In critically ill patients immunonutrition may decrease infectious
      complications but it is not associated with a mortality advantage. Pediatric
      experience is limited, but the future is promising.

PMID- 12061677
TI  - Dietary management of inborn errors of metabolism.
AB  - Inborn errors of metabolism are individually rare but are an important cause of
      mortality and morbidity in infants and children. Dietary therapy is the mainstay
      of treatment in phenylketonuria, maple syrup urine disease, homocystinuria,
      galactosemia and glycogen storage disease (Type I/III). Some disorders like urea
      cycle disorders and organic acidurias require dietary modification in addition to
      other modalities. Certain basic principles of dietary management should be
      clearly understood for proper management of these disorders. Commercially
      available diets are very expensive and modification in routine Indian diet may be
      tried based on content of different nutrients but the desirable fine control is
      not achieved.

PMID- 12061678
TI  - Nutrition management in chronic liver disease.
AB  - Liver has a central role in nutritional homeostasis and any liver disease leads
      to abnormalities in nutrient metabolism and subsequent malnutrition. All children
      with chronic liver disease (CLD) must undergo a periodic nutritional assessment-
      medical history, anthropometry esp. skinfold thickness and mid-arm circumference,
      and biochemical estimation of body nutrients. Nutritional rehabilitation is
      catered to the individual child but generally the caloric intake is increased to
      130% of RDA by adding glucose polymers and/or MCT oil (coconut oil) with
      essential fatty acid supplementation (sunflower oil). The enteral route is
      preferred and occasionally nasogastric and/or nocturnal feeding are required to
      ensure an adequate intake. Proteins rich in branched chain amino acids are given
      in moderation (2-3 gm/kg/day) in compensated cirrhotics unless encephalopathy
      occurs when protein restriction may be necessary (1 gm/kg/day). Fat-soluble
      vitamins are supplemented in large quantities esp. in cholestasis along with
      other vitamins and minerals. Dietary therapy is the mainstay of management of
      some metabolic liver diseases and may be curative in disorders like galactosemia,
      fructosemia and glycogen storage disorders. Pre and postoperative nutritional
      support is an important factor in improving survival after liver transplantation.

PMID- 12061679
TI  - Bilateral Swyer-James (Macleod's) syndrome.
AB  - Swyer James syndrome (SJS) is a rare disorder. It is generally discovered on a
      chest radiograph as increased translucency involving one hemithorax with
      diminished vascular markings. We present a 5-year-old girl admitted for the
      treatment of recurrent bronchiolitis. She was diagnosed as having Swyer James
      syndrome from the results of CT scan and ventilation perfusion scintigraphy,
      which revealed unsuspected bilateral involvement. This condition should be
      considered as a differential diagnosis in a patient with Swyer James (Macleod's)
      syndrome without an obvious etiology.

PMID- 12061680
TI  - Glial choristoma.
AB  - Glial choristoma is a developmental malformation of heterotopic central nervous
      tissue with limited growth potential. It is considered to be one of the very rare
      choristomatous lesions involving the oral cavity. This report details the
      morphological characteristics of glial choristoma arising from the palate in a
      newborn. Bulk of the tissue comprised of mature neuroglial tissue with astrocytes
      representing developing brain, cystic spaces lined by cuboidal epithelium
      indicating ependymal layer. Clinical features, associated malformations and
      histomorphology of this lesion is discussed.

PMID- 12061681
TI  - Subclavian artery supply disruption sequence-Klippel-Feil and Mobius anomalies.
AB  - Fetal vascular disruptions can cause specific patterns of birth depending on the
      location, extent and timing of the disruptive event in the embryonic life. An
      example of this is subclavian artery supply disruption sequence occurring around
      6 weeks of gestation which causes various combinations of Poland, Klippel-Feil
      and Mobius anomalies. A one-month-old child with features of all three anomalies
      along with other associated features is described here.

PMID- 12061683
TI  - Shah Waardenberg syndrome.
AB  - Intermittent or partial small bowel obstruction in a neonate may be a rare
      presentation of total aganglionosis. The presence of partial albinism and white
      forelock should alert the clinician to the possibility of associated Hirschsprung
      disease as a cause of bowel symptoms. Such a rare association has been called
      Shah Waardenberg syndrome and is being reported.

PMID- 12061684
TI  - Kleine-Levin syndrome following acute non-specific encephalitis.

PMID- 12061682
TI  - Selenium in the neonate.
AB  - Selenium is a trace element of tremendous importance in human health. It is a
      constituent of the antioxidant enzyme. Glutathione peroxidase and therefore is
      vital to antioxidant defense. Several diseases of the neonate have been shown to
      be caused at least in part by oxygen free radicals. These include
      bronchopulmonary dysplasia retinopathy of prematurity necrotising enterocolitis
      patient ductus arteriosus and neuronal injury of hypoxic ischemic encephalopathy.
      Good selenium nutrition is therefore of key importance to antioxidant defense in
      the neonate. The communique reviews the important role that selenium might play
      in neonatal health & disease.

PMID- 12061685
TI  - Efficacy of cholangiography under helical computed tomography for laparoscopic
      cholecystectomy.
AB  - PURPOSE: Although laparoscopic cholecystectomy (LC) is known to be safe, the
      optimal imaging technique for examining the common bile duct and cystic duct
      prior to laparoscopic intervention remains controversial. The objective of this
      study was to evaluate the efficacy of cholangiography under helical computed
      tomography (helical CT cholangiography) for LC. METHODS: We studied 53
      consecutive patients who underwent LC carried out by the same surgeon. The data
      of 23 of these patients who had undergone LC before the introduction of helical
      CT were used as the reference standard. Among the 53 patients, 28 were
      prospectively randomized for preoperative biliary tract evaluation with versus
      without helical CT cholangiography, into a CT/+ group (n = 13) and a CT/- group
      (n = 15), respectively. Two patients were excluded from the study preoperatively.
      RESULTS: There were no significant differences in age or laboratory findings,
      including liver function tests or the serum amylase level before or after
      surgery, between the two groups. In the CT/- group, endoscopic retrograde
      cholangiography-related pancreatitis developed in one patient, and one patient
      required conversion to open surgery. In contrast, in the CT/+ group, there were
      no preoperative complications and no patient required conversion to open surgery.
      The mean operative time was significantly shorter in the CT/+ group than in the
      CT/- group (P = 0.0137). CONCLUSION: These findings provide evidence to support
      the advantages of helical CT cholangiography in relation to operative time,
      conversion, and procedure-related preoperative complications.

PMID- 12061686
TI  - Risk of missing colorectal cancer during laparoscopic cholecystectomy.
AB  - PURPOSE: The increased number of patients undergoing laparoscopic cholecystectomy
      (LC) is associated with a risk of missing concomitant colorectal cancers;
      however, the incidence and cause have not yet been well recognized. Our aim,
      therefore, was to evaluate these factors. METHODS: This retrospective study
      evaluated data on 473 patients with benign gallbladder diseases, who underwent LC
      between January 1991 and December 1999. Among these 473 patients, 2 (0.4%) were
      thought to have had detectable cancer at LC. RESULTS: The first patient was a 59
      year-old woman who underwent palliative resection for ascending colon cancer
      associated with liver and pulmonary metastases 10 months following LC when
      laboratory data showed a low hemoglobin level (10.0 g/dl). The other patient, a
      50-year-old man, underwent resection for Dukes' C sigmoid colon cancer 6 months
      following LC. At LC, the patient did not present with any symptoms suggesting the
      existence of colorectal cancer and the laboratory data were normal. CONCLUSIONS:
      These results indicate that although an extremely low incidence of missed
      colorectal cancers does not justify routine screening for colorectal cancer
      before LC in terms of cost-effectiveness, careful attention to preoperative
      physical findings and laboratory data as well as meticulous techniques and full
      diagnostic visualization of the large-bowel intraoperatively may reduce the
      potential risk of missing coexisting colorectal cancers during LC.

PMID- 12061687
TI  - Superficial thrombophlebitis of the lower limbs in patients with varicose veins.
AB  - PURPOSE: This study reviews 51 consecutive patients with superficial
      thrombophlebitis (STP) among 710 patients treated for varicose veins in our
      department. Methods. An assessment was made of various factors involved. RESULTS:
      Of these 51 patients, 21 (41.1%) had systemic disorders, including 4 (7.8%) with
      malignant diseases. Six patients (11.8%) had deep vein thrombosis (DVT) and five
      (9.8%) had pulmonary embolism (PE). All of the patients with DVT and/or PE had a
      thrombus in either the greater saphenous vein or the lesser saphenous vein;
      however, none of the patients with STP and a thrombus in the distal saphenous
      branch had either DVT or PE. The levels of coagulofibrinolytic markers such as
      fibrin degradation product-D dimer, plasmin alpha plasmin inhibitor complex, and
      thrombin antithrombin III complex were elevated in patients with STP or DVT,
      compared with those with varicose veins only. The level of C-reactive protein
      (CRP) was also elevated in the patients with STP or DVT. These findings indicate
      that STP is not necessarily a localized disease, but may be a symptom of systemic
      disease. In addition to duplex scanning, the measurement of coagulofibrinolytic
      markers as well as CRP may be useful for detecting STP and/ or DVT prior to the
      treatment of varicose veins.

PMID- 12061688
TI  - Endobronchial lipoma accompanied with primary lung cancer: report of a case.
AB  - A 72-year-old man was found to have an endobronchial lipoma accompanied with
      primary lung cancer. A left lower lobectomy with a mediastinal lymph node
      dissection and a sleeve resection of the lingual bronchus with telescoping
      bronchial anastomosis were done. The pathological staging was T1N2M0, stage IIIA.
      A histological examination showed well-differentiated squamous cell carcinoma in
      segment 10, in addition to the presence of mature adipose tissue which was
      diagnosed to be a benign endobronchial lipoma originating from the lingual
      bronchus. The postoperative course was uneventful and the patient was discharged
      13 days after the operation. However, he had a recurrence in the subcarinal lymph
      node, and died 8 months after surgery.

PMID- 12061689
TI  - Giant localized solitary fibrous tumors of the diaphragmatic pleura: report of
      two cases.
AB  - We report two cases, of 48- and 53-year-old women, with huge intrathoracic
      extrapulmonary tumors which originated from the diaphragm. In these cases the
      totally resected tumors were examined histologically and immunohistochemically,
      and based on these studies benign localized solitary fibrous tumors originating
      from the diaphragmatic pleura were diagnosed. We observed no recurrence in the
      long-term follow-up, which was necessary for these cases due to the tumors'
      unpredictable clinical behavior even when they were thought to be benign
      histologically. Because of the huge sizes of these tumors, originating from the
      diaphragmatic pleura with pedicles, and benign clinical outcome correlating with
      the histological examination, these cases are thought to be worthy of interest.

PMID- 12061690
TI  - Pericardial-peritoneal window for chronic exudative pericarditis using a
      subxiphoidal approach: report of three cases.
AB  - From August 1986 to February 2000, three patients were given a pericardial
      peritoneal window using a subxiphoidal approach, for pericardial effusion
      associated with chronic exudative pericarditis. Complete drainage without
      recurrence was achieved in two patients with a large pericardial-peritoneal
      window (4 cm diameter) and effusion recurred in another with a small pericardial
      peritoneal window (3cm diameter). No complications were encountered. The
      pericardial-peritoneal window, approached subxiphoidally, is a simple, safe, and
      effective procedure and applicable in most patients with non-infectious benign
      pericardial effusion. We herein describe our techniques, clinical
      characteristics, and the results for three patients undergoing this treatment.

PMID- 12061691
TI  - Aortocaval fistula complicated with bacteremia due to Escherichia coli: report of
      a case.
AB  - We herein report a case of aortocaval fistula complicated with bacteremia due to
      Escherichia coli in a 78-year-old man who underwent an emergency operation. A
      surgical resection of the abdominal aortic aneurysm with a closure of the
      fistula, and reconstruction with an expanded polytetrafluoroethylene bifurcated
      graft and wrapping with an omental flap, were performed followed by a 9-week
      continuous administration of antibiotics. Thereafter, antifungal agents were
      administered and the results were good. Both an early diagnosis and prompt
      surgery are important for such patients, and long-term administration of
      antibacterial agents is also necessary.

PMID- 12061692
TI  - Dissecting aneurysm of the infrarenal abdominal aorta: report of a case.
AB  - A primary abdominal aortic dissection is exceedingly rare, especially in the
      absence of blunt abdominal trauma. We herein report a case of aortic dissection
      with aneurysmal dilatation (dissecting aneurysm) of the infrarenal abdominal
      aorta in a 61-year-old female patient, and discuss the diagnostic and therapeutic
      management of this rare disorder.

PMID- 12061693
TI  - Spontaneous esophageal rupture successfully treated by conservative therapy:
      report of two cases.
AB  - Spontaneous esophageal rupture is a life-threatening condition for which surgical
      intervention within 24h after the onset is usually recommended. This report
      describes two cases of spontaneous esophageal rupture successfully treated by
      conservative therapy. In the first case, a 68-year-old man was hospitalized for
      severe upper abdominal pain following hematemesis. A large left pleural effusion
      occurred the next day and spontaneous esophageal rupture was diagnosed 1 week
      later, following placement of an intrathoracic drain. In the second case, a 38
      year-old man was admitted for severe back pain following vomiting and esophageal
      rupture diagnosed within 3 h after onset by computed tomography (CT), which
      showed left pleural effusion, pneumothorax, and pneumomediastinum. Both patients
      were successfully treated conservatively with continuous intrathoracic drainage,
      intravenous antibiotics, and hyperalimentation. We conclude that spontaneous
      esophageal rupture can be treated conservatively under intensive observation.

PMID- 12061694
TI  - Retained surgical sponge presenting as a gastric outlet obstruction and duodeno
      ileo-colic fistula: report of a case.
AB  - An unusual case of a retained surgical sponge migrating to the duodenum causing
      gastric outlet obstruction and duodeno-ileo-colic fistula is reported.

PMID- 12061695
TI  - Solitary intraperitoneal recurrence of alpha-fetoprotein-producing gastric
      carcinoma: report of a case.
AB  - A solitary recurrence of gastric carcinoma in the peritoneal cavity is extremely
      rare. We herein present a case of solitary intraperitoneal recurrence in a
      patient with alpha-fetoprotein (AFP)-producing gastric carcinoma. As far as we
      can determine, this is the first report of such a form of recurrence in a patient
      with gastric carcinoma who underwent a successful resection. A review of our
      eight patients who had AFP-producing gastric carcinoma showed a frequent
      association with hepatic metastasis and a poor prognosis as has been reported
      previously. Our patient received intra-arterial chemotherapy with low-dose
      cisplatin and 5-fluorouracil to prevent hepatic recurrence, but eventually
      developed multiple hepatic metastases after ceasing this therapy. Therefore,
      adjuvant intra-arterial chemotherapy may have altered the site of first
      recurrence in this patient.

PMID- 12061696
TI  - Leiomyosarcoma of the greater omentum with liver metastasis: report of a case.
AB  - We report herein a rare case of leiomyosarcoma arising from the greater omentum
      with concomitant liver metastases. A 63-year-old Japanese woman was admitted to
      our hospital with an elastic-hard mass in the abdomen, but no other symptoms. The
      findings of several examinations led us to suspect an omental leiomyosarcoma. A
      laparotomy revealed an elastic hard and foliaceous mass (12.5 x 9.0 x 8.0 cm)
      arising from the omentum, and six masses in the liver. The omental tumor was
      extirpated and chemotherapy was administered under the guidance of angiography.
      The final diagnosis was leiomyosarcoma of the omentum. About 9 months after the
      operation, multiple liver metastases were found and repeated chemotherapy was
      given, but without effect. A partial hepatectomy was done, accompanied by
      microwave coagulation therapy (MCT). She is currently well and asymptomatic, with
      no signs of recurrence, 1 year after the partial hepatectomy. Thus, surgical
      resection and MCT were effective against liver metastases of a leiomyosarcoma in
      this patient.

PMID- 12061697
TI  - Adenocarcinoma with extensive neuroendocrine differentiation arising in an ileal
      diverticulum: report of a case.
AB  - A 62-year-old man presented with right-sided abdominal pain. Radiologic
      examinations disclosed a solid tumor in the ileocecal mesentery that obstructed
      the right ureter, thus resulting in urinary extravasation. An en bloc tumor
      resection with the ascending colon, the terminal ileum, and a portion of the
      right ureter was performed. Histopathologically, the tumor was adenocarcinoma
      with extensive neuroendocrine differentiation which had arisen in an ileal
      diverticulum. The patient developed metastases to the lymph nodes, liver, and
      brain, and died 18 months after surgery.

PMID- 12061698
TI  - Psoas abscess as a complication of pyogenic sacroiliitis: report of a case.
AB  - A psoas abscess is, either primary or secondary, a rare entity for a general
      surgeon. Images by ultrasonography and computed tomography (CT) can help a
      general surgeon to make an accurate diagnosis when encountering the patient
      complaining of unilateral lower abdominal deep pain with fever. A case of
      pyogenic abscess of the psoas muscle as a result of sacroiliitis in a 22-year-old
      man is reported herein. The abdominal CT and magnetic resonance imaging scans
      demonstrated a large multilocular abscess extending along the iliopsoas muscle,
      and erosion and a widening of the left sacroiliac joint. The abscess was drained
      with an open surgical approach and the patient responded well to antibiotic
      therapy. Aggressive surgical and medical treatment is necessary in patients with
      psoas abscess to prevent complications.

PMID- 12061700
TI  - Spontaneous liver hematoma and a hepatic rupture in HELLP syndrome: report of two
      cases.
AB  - Subcapsular liver hematomas and ruptures are unusual fatal complications of HELLP
      (hemolysis, elevated liver enzymes, and low platelets) syndrome (HS). We present
      two cases of a spontaneous rupture of subcapsular liver hematoma occurring in HS
      and review the literature on this subjects. One case demonstrated a secondary
      rupture of a subcapsulary liver hematoma due to HS in one patient and HS
      associated with preeclampsia in another. The defects were on the medial and
      lateral sectors of the left lobe in one patient and on the medial sector of the
      right lobe in the other patient. In case 1 deep mattress sutures and omentoplasty
      were performed, and in the other case a defective area was closed with an
      absorbable gelatin sponge with a hemostatic effect. In addition, the liver was
      compressed by abdominal towels. A high index of suspicion and immediate
      recognition are keys to proper diagnosis and management of affected patients. The
      multidisciplinary approach to the management of these patients led to a
      remarkable decrease in the mortality rates. Less aggressive treatment is
      preferable to aggressive intervention such as a hepatic resection in such
      patients with coagulopathy.

PMID- 12061699
TI  - Primary hepatic leiomyosarcoma in a woman after renal transplantation: report of
      a case.
AB  - In contrast to malignant lymphomas or skin cancer, smooth muscle tumors including
      leiomyosarcoma are rarely associated with transplant recipients. We herein
      present a 33-year-old woman with end-stage renal disease who received a
      transplant at 27 years of age. Four years after the transplantation, at age 31,
      she underwent a mastectomy because of primary right breast cancer, which was
      found to be a 5-mm-sized mucinous carcinoma with no regional lymph node
      metastasis. Six years after the transplantation, a liver tumor was unexpectedly
      discovered. An explorative laparotomy revealed a well-encapsulated tumor
      occupying the posterior portion of the right lobe of the liver. The patient
      underwent a posterior segmentectomy. Histologically, the tumor possessed
      intermingling fascicles of spindle cells with eosinophilic cytoplasm and
      elongated nuclei. Based on an immunohistochemical examination, the tumor cells
      were positive for the muscle-associated antibody. In addition, RNA probes for
      Epstein-Barr virus were negative based on in situ hybridization. The histologic,
      immunohistochemical findings were considered to be diagnostic for leiomyosarcoma,
      which is a low-grade malignancy. Two years after surgery, the patient is doing
      well with no recurrence of liver tumors or breast cancer.

PMID- 12061701
TI  - Liver abscess formation after microwave coagulation therapy applied for hepatic
      metastases from surgically excised bile duct cancer: report of a case.
AB  - We report the case of a liver abscess associated with microwave coagulation
      therapy (MCT). A 67-year-old man underwent a pylorus-preserving
      pancreatoduodenectomy for bile duct cancer in August 1998. In June 1999,
      abdominal computed tomography (CT) showed three low-density areas in his liver.
      With a diagnosis of multiple metastatic liver tumors, we applied MCT to each
      liver tumor. The patient presented with fever after therapy. Abdominal CT showed
      a hepatic abscess, which was treated by percutaneous transhepatic abscess
      drainage under ultrasonography. A bacteriological examination of the pus material
      revealed the presence of Enterococcus faecalis and Candida albicans. Treatment
      resulted in a rapid resolution of symptoms. Our case indicated that care should
      be exercised in using MCT for the treatment of liver tumors in patients who have
      undergone reconstructive surgery of the biliary tract.

PMID- 12061702
TI  - Metastatic biliary polypoid thrombus from renal cell carcinoma: report of a case.
AB  - We report an extremely rare case of metastatic biliary polypoid thrombus with
      hepatic metastases from renal cell carcinoma. A 74-year-old man was admitted with
      a low-grade fever and obstruction of the left hepatic duct. He had undergone left
      nephrectomy 17 years previously due to a diagnosis of renal cell carcinoma. A
      preoperative diagnosis of left hepatic duct carcinoma was made, and a left
      lobectomy and left caudate lobectomy with right biliary anastomosis of jejunal
      loop were performed. The resected specimen showed a polypoid mass in the left
      hepatic duct with metastases in the caudate lobe, and a histological examination
      revealed both tumors to be clear cell-type renal cell carcinoma. The mechanism of
      biliary metastatic thrombus formation was speculated to be as follows: caudate
      lobe metastases invade the adjacent bile ducts, and a tumor fragment in the bile
      duct then becomes implanted in the intraluminal left hepatic duct, thus leading
      to the growth of the biliary polypoid thrombus.

PMID- 12061703
TI  - So-called carcinosarcoma of the gallbladder; spindle cell carcinoma of the
      gallbladder: report of a case.
AB  - We report a so-called carcinosarcoma of the gallbladder in a 53-year-old man. The
      findings of ultrasonography, computed tomography, endoscopic retrograde
      cholangiopancreatography, and angiography revealed a large mass of the
      gallbladder with a cholesterol stone. He underwent three operations, and died
      from liver failure with multiple liver metastasis immediately after the third
      operation. A pathological examination revealed neoplastic tissue composed of
      sarcomatous and glandular components. Hematoxylin-eosin stain proved the presence
      of carcinosarcoma in the gallbladder, but an immunohistochemical study proved
      that the sarcomatous component was stained by antivimentin and also
      anticytokeratin antibodies, which thus proved it to be so-called carcinosarcoma
      of the gallbladder. As a result, an immunohistochemical study is considered to
      provide valuable information regarding the identification of sarcomatous elements
      in such cases.

PMID- 12061704
TI  - Pancreaticoduodenectomy for perforated gastric malignant lymphoma: report of a
      case.
AB  - We herein report the case of a 65-year old man with gastroduodenal malignant
      lymphoma (diffuse large B-cell type) accompanied with a bulbar perforation. A
      pancreaticoduodenectomy was performed because the duodenal second portion and
      pancreatic head were involved. However, extensive lymphadenectomy was not carried
      out because many lymph nodes were involved. The postoperative course was
      uneventful and CHOP therapy (pirarubicin 30 mg/m2, cyclophosphamide 500 mg/m2,
      vincristine 1 mg/m2, prednisolone 30 mg/m2) was started 1 month after surgery.
      Seven cycles of CHOP therapy markedly reduced the residual lesions including
      lymph nodes, and a computed tomography scan after the final chemotherapy revealed
      no obvious lesions. Complete remission was obtained and the patient was
      discharged 9 months after surgery.

PMID- 12061705
TI  - Acutely exaggerated hepatitis B induced by the withdrawal of immunosuppressants
      in a seroconverted renal transplant recipient: report of a case.
AB  - The long-term reciprocal impact of renal transplantation on infection by
      hepatitis B virus (HBV) is still a matter of intense debate, and the topic
      remains controversial. We herein report the case of a 50-year-old male
      asymptomatic HBV carrier who had seroconverted to positive anti-HBe antibody (Ab)
      and received a kidney transplantation from a cadaver donor (HB surface(s) antigen
      (Ag)-negative). Nine months later, his kidney function deteriorated due to
      chronic rejection, and hemodialysis was temporarily required. Triple drug therapy
      (cyclosporine, prednisolone, azathioprine) for immunosuppression was changed to
      two-drug therapy (cyclosporine and prednisolone) at a reduced dosage because of
      this episode. After that episode, severe hepatitis with HBV antigenemia developed
      without any change in the serological state. The levels of DNA polymerase in a
      potential recipient from a cadaveric donor should be checked before
      transplantation to predict the occurrence of hepatitis when the recipient is an
      asymptomatic carrier of HBV, especially in cases of serologically HBeAg-negative,
      and anti-HBeAb-positive carriers.

PMID- 12061706
TI  - Translations of the humerus in persons with shoulder impingement symptoms.
AB  - STUDY DESIGN: Two-group mixed-model analysis of covariance and correlation
      analysis. OBJECTIVES: To determine whether differences in humeral translations
      exist between patients with shoulder impingement symptoms and an asymptomatic
      comparison group, and if so, to determine if shoulder range-of-motion (ROM)
      measures are associated with abnormal translations. BACKGROUND: Abnormal
      translations of the humeral head are believed to reduce the available subacromial
      space and to contribute to the development or progression of shoulder impingement
      symptoms. These abnormal translations have also been theorized to be related to
      tightness of the posterior capsule and decreased shoulder ROM. METHODS AND
      MEASURES: Three-dimensional humeral translations were tracked in symptomatic
      construction workers and an asymptomatic comparison group while elevating the arm
      in the scapular plane under no-load, 2.3-kg, and 4.6-kg hand-load conditions.
      Between-group comparisons were made across 3 phases of motion (30 degrees-60
      degrees, 60 degrees-90 degrees, and 90 degrees-120 degrees) and the association
      between humeral translations and cross-body adduction and shoulder internal
      rotation ROM measures were determined by Pearson correlation analysis. RESULTS:
      Persons with shoulder symptoms demonstrated small but significant changes in
      anterior-posterior translations of the humerus. These changes for the 90 degrees
      120 degrees phase of humeral elevation were moderately negatively associated with
      available cross-body adduction ROM. CONCLUSIONS: The identified kinematic
      deviations are consistent with possible reductions of the subacromial space.
      Further study of relationships between posterior capsule tightness, rotator cuff
      function, and abnormal humeral translations is warranted to better delineate
      underlying kinematic mechanisms that may contribute to shoulder impingement
      symptoms and to refine rehabilitation techniques.

PMID- 12061707
TI  - Outcomes of total hip arthroplasty: a study of patients one year postsurgery.
AB  - STUDY DESIGN: Ex post facto research using prospective analysis of differences
      between the involved hip and uninvolved hip. OBJECTIVES: To assess outcomes of
      total hip arthroplasty (THA) by comparing range of motion (ROM), muscle strength,
      and postural stability in the surgical hip to those of the uninvolved hip 1 year
      postsurgery. An additional objective was to assess degree of relationship among
      ROM, strength, and postural stability impairments to a measure of self-assessed
      function. BACKGROUND: Most patients who have THA receive physical therapy that
      consists mainly of self-care instructions and an exercise protocol that
      emphasizes mobility during the acute phase of recovery. But, outcomes of THA 1
      year postsurgery indicate that current physical therapy programs used during the
      acute phase of recovery do not effectively restore physical and functional
      performance. METHODS AND MEASURES: Subjects consisted of 11 women and 4 men (mean
      age +/- standard deviation = 62 +/- 8 years) with unilateral THA performed 1 year
      prior to data collection. Assessment variables consisted of self-assessment of
      function and measures of postural stability, muscle strength, and hip ROM. The 12
      Item Hip Questionnaire was used for self-assessment of function. Three separate
      repeated measures MANOVA were used to compare the involved side to the uninvolved
      side in measures of postural stability, strength, and ROM. The Spearman's rho was
      used to assess degree of association between the subjects' score of self-assessed
      function and impairments in strength and postural stability. RESULTS: Measures of
      postural stability were significantly lower (P < or = 0.01) on the side of the
      replaced hip. Differences in strength values between the involved and uninvolved
      sides were not statistically significant. Correlations between scores of self
      assessed function and hip abductor and knee extensor strength were statistically
      significant (r = 0.56, P < or = 0.03). Self-assessed function was not
      significantly correlated to postural stability impairments. CONCLUSION: The brief
      postsurgical rehabilitation program received by patients with THA may not be
      sufficient. A second phase of rehabilitation implemented 4 months or more after
      surgery that emphasizes weight bearing and postural stability may be advisable.

PMID- 12061708
TI  - Rehabilitation following thermal-assisted capsular shrinkage of the glenohumeral
      joint: current concepts.
AB  - Glenohumeral joint instability is a common pathology observed in the orthopedic
      and sports medicine settings. Overhead athletes often exhibit a certain degree of
      acquired laxity that can lead to various pathologies. Unfavorable results often
      observed with traditional open procedures to correct instability in the overhead
      athlete have led to the development of arthroscopic thermal-assisted capsular
      shrinkage (TACS). TACS is not commonly used as an isolated procedure in overhead
      athletes; various procedures are often performed concomitantly. The overall
      outcome greatly depends on a postoperative rehabilitation program that must be
      assessed and adjusted frequently based on several factors. Knowledge of the basic
      science of TACS as well as emphasis on dynamic stabilization, proprioception, and
      neuromuscular control are vital to the rehabilitation program for overhead
      athletes. The purpose of this paper is to discuss the basic science and clinical
      application of thermal-assisted capsular shrinkage of the glenohumeral joint as
      well as the postoperative rehabilitation for the overhead athlete and the patient
      with congenital laxity and related multidirectional instability.

PMID- 12061709
TI  - Interval sport programs: guidelines for baseball, tennis, and golf.
AB  - In using an ISP in conjunction with a structured rehabilitation program, the
      athlete should be able to return to full competition status. The general
      guidelines and specific programs outlined are used to minimize the chance of
      reinjury and to facilitate the return of function and confidence in the athlete.
      The program and its progression should be modified to meet the specific needs of
      each individual athlete. A comprehensive program consisting of a propter
      maintenance rehabilitation program incorporating strengthening, flexibility,
      plyometric, dynamic stabilization, and neuromuscular controls drills, as well as
      appropriate warm-up procedures and biomechanics, is essential in returning
      athletes to competition as quickly and safely as possible.

PMID- 12061710
TI  - Structure of polydispersed colloids characterised by light scattering and
      electron microscopy.
AB  - The dynamics of growth and aggregation of colloidal silver iodide particles was
      followed by the static light scattering method. The particles were treated as
      spheres and they were stable in size in the defined time interval. This approach
      enabled the use of the Zimm plots in order to determine the radii of gyration and
      the radii of spherical particles. Stable AgI colloids, either positively or
      negatively charged, showed the usual Zimm diagrams, while the diagrams were
      untypical when the stability of the colloids decreased. The untypical Zimm
      diagrams showed 'curves' with envelopes and 'curves' with minima in the unstable
      domain and in the domain where the most rapid nucleation occurs, respectively.
      Satisfactory agreement of particle sizes within the limits of accuracy,
      determined using static--and dynamic light scattering data and of the values
      obtained from the electron microscopic images was shown. Fitting the theoretical
      and experimental data, P(theta) functions showed that the particle shapes
      approach the theoretical model for spheres and thin discs. The colloid stability
      of polydispersed aggregates was also explained using the second virial
      coefficient, its negative sign implying interaction of particles in the solution,
      its positive value indicating formation of new particles from the supernatant
      solution. In addition, the colloid stability can be characterised by the mass
      fractal dimension. For positive stable colloids, Dm = 2.70 +/- 0.26, it can be
      related to the reaction controlled processes, whereas for negative stable
      colloids, Dm = 1.97 +/- 0.19, it was attributed to the diffusion controlled
      processes.

PMID- 12061711
TI  - Effects of structural rearrangements on the rheology of rennet-induced casein
      particle gels.
AB  - During ageing of casein or skim milk gels, structural changes take place that
      affect gel parameters, such as pore size and storage modulus. These changes can
      be explained in terms of rearrangements of the gel network at various length
      scales. In this paper, rheological experiments on rennet-induced casein gels and
      a general model on rearrangements are presented. The results of experiments (e.g.
      microscopy, permeametry) and computer simulations, the model, and recent
      literature on casein gels and other types of particle gels are compared to each
      other. Experiments presented include measurements of storage and loss moduli and
      maximum linear strain of the casein gels. Parameters varied were pH (5.3 and
      6.65) and temperature (25 and 30 degrees C). In addition, the casein volume
      fraction (5-9 vol.%) was varied, which enables application of fractal scaling
      models. For rennet-induced casein gels, it is demonstrated that at the lower pH,
      all types of rearrangements proceed significantly faster. The rearrangements
      include: an increase in the size of compact building blocks; partial
      disappearance of fractal structure; and the formation of straightened strands,
      some of which eventually break. All of these rearrangements seem to be a
      consequence of particle fusion. There are indications of universality of the
      relation between particle fusion and gel syneresis for gels composed of
      viscoelastic particles.

PMID- 12061712
TI  - Energy of interaction in colloids and its implications in rheological modeling.
AB  - This work deals with the problem of deriving theoretical connections between
      rheology and interparticle forces in colloidal suspensions. The nature of
      interparticle forces determines the colloidal structure (crystalline order due to
      long range repulsive forces, flocculation due to attractive forces, etc.) and
      hence, the flow behavior of suspensions. The aim of this article is to discuss
      how these interactions enter the modeling of rheometric functions, in particular,
      the shear viscosity. In this sense, the main interactions commonly appearing in
      colloids are reviewed, as well as the role they play in phase transition
      behavior. Then, a series of approaches relating the interaction potential to
      viscosity is examined. The results of applying these models to experimental data
      are also discussed. Finally, examples of viscosity modeling for different
      interaction potentials are given, by using the structural model proposed
      previously by the authors. The possibility of relating the flow behavior of
      colloidal suspensions to the interaction between particles offers new
      perspectives for the study and technical applications of these systems.

PMID- 12061713
TI  - Determination of the glycosidic torsion angles in uniformly 13C-labeled nucleic
      acids from vicinal coupling constants 3J(C2)/4-H1' and 3J(C6)/8-H1'.
AB  - A two-dimensional, quantitative J-correlation NMR experiment for precise
      measurements of the proton-carbon vicinal coupling constants 3J(C2)/4-H1' and
      3J(C6)/8-H1' in uniformly 13C-labeled nucleic acids is presented. To reduce loss
      of signal due to 1H-13C dipole-dipole relaxation, a multiple-quantum constant
      time experiment with appropriately incorporated band selective 1H and 13C pulses
      was applied. The experiment is used to obtain the 3J(C2)/4-H1' and 3J(C6)/8-H1'
      coupling constants in a uniformly 13C, 15N-labeled [d(G4T4G4)]2 quadruplex. The
      measured values and glycosidic torsion angles in the G-quadruplex, obtained by
      restrained molecular dynamics with explicit solvent using the previously
      published restraints, along with selected data from the literature are used to
      check and modify existing parameters of the Karplus equations. The
      parameterizations obtained using glycosidic torsion angles derived from the
      original solution and recently determined X-ray structures are also compared.

PMID- 12061714
TI  - Quantitation of movement of the phosphoryl group during catalytic transfer in the
      arginine kinase reaction: 31P relaxation measurements on enzyme-bound equilibrium
      mixtures.
AB  - 31P nuclear spin relaxation measurements have been made on enzyme-bound
      equilibrium mixtures of lobster-muscle arginine kinase in the presence of
      substituent activating paramagnetic cation Co(II) (in place of Mg(II)), i.e., on
      samples in which the reaction, E.CoATP.arginine <=> E.CoADP.P-arginine, is in
      progress. The results have been analyzed on the basis of a previously published
      theory (Nageswara Rao, B.D. (1995) J. Magn. Reson., B108, 289-293) to determine
      the structural changes in the reaction complex accompanying phosphoryl transfer.
      The analysis enables the determination of the change in the Co(II)-31P (gamma
      P(ATP)) vector as the transferable phosphoryl group moves over and attaches to
      arginine to form P-arginine. It is shown that the Co(II)-31P distance of
      approximately 3.0 A, representing direct coordination of Co(II) to gamma-P(ATP),
      changes to approximately 4.0 A when P-arginine is formed in the enzyme-bound
      reaction complex. This elongation of the Co(II)-31P vector implies an excursion
      of at least 1.0 A for the itinerant phosphoryl group on the surface of the
      enzyme.

PMID- 12061715
TI  - Practical aspects of the 2D 15N-[1h]-NOE experiment.
AB  - The heteronuclear 15N-NOE experiment was extensively tested with respect to
      statistical and systematic experimental error. The dependence of signal intensity
      in the NOE experiment and in the reference experiment on the saturation and
      relaxation time was experimentally investigated. The statistics of the
      experimental values were accessed by numerous repetitions of identical set-ups.
      As a model system a protein of typical size for NMR studies was chosen, i.e., a
      120 amino acid residues containing fragment of the F-actin binding gelation
      factor (ABP-120). The fragment exhibits fast dynamics that are accessible with
      the 15N-NOE experiment with various amplitudes. The results of this study show
      that commonly used parameters are only adequate for accurate measurement of
      motions with moderate amplitude. Highly flexible parts require longer delay times
      and thus more experimental time than commonly used. On the other hand, a
      qualitative or semi-quantitative assessment of a protein's mobility on fast times
      scales can be obtained from rapidly recorded experiments with unusual short delay
      times. The findings of this study are of equal importance for highly accurate
      measurement of the 15N-NOE as well as for quick identification of mobile or even
      unstructured residues/parts of a protein.

PMID- 12061716
TI  - Effect of deuteration on some structural parameters of methyl groups in proteins
      as evaluated by residual dipolar couplings.
AB  - One bond methyl 1H-13C and 13Cmethyl-13C scalar and residual dipolar couplings
      have been measured at sites in an 15N, 13C, approximately 50% 2H labeled sample
      of the B1 immunoglobulin binding domain of peptostreptococcal protein L to
      investigate changes in the structure of methyl groups in response to deuterium
      substitution. Both one bond methyl 1H-13C and 13Cmethyl-13C scalar coupling
      constants have been found to decrease slightly with increasing deuterium content.
      Previous studies have shown that 1H-13C couplings in methyl groups are
      exquisitely sensitive to electronic structure, with decreases in coupling values
      as a function of deuteration consistent with a slight lengthening of the
      remaining H-C bonds. Changes in the HmethylCmethylC angle are found to be small,
      with average differences on the order of 0.3+/-0.1 degrees and 0.4+/-0.2 degrees
      between CH3, CH2D and CH3, CHD2 isotopomers, respectively. Knowledge of methyl
      geometry is a prerequisite for the extraction of accurate dynamics parameters
      from spin relaxation studies involving these groups.

PMID- 12061717
TI  - Angular dependence of 1J(Ni,Calphai) and 2J(Ni,Calpha(i-1)) coupling constants
      measured in J-modulated HSQCs.
AB  - A new method to measure 1J(Ni,Calphai) and 2J(Ni,Calpha(i-1)) coupling constants
      in proteins based on a J-modulated sensitivity enhanced HSQC was introduced.
      Coupling constants were measured in the denatured and in the native state of
      ubiquitin and found to depend on the conformation of the protein backbone. Using
      a combined data set of experimental coupling constants from ubiquitin and
      staphylococcal nuclease (Delaglio et al., 1991), the angular dependence of the
      coupling constants on the backbone angles psi and phi was investigated. It was
      found that the size of 2J(Ni,Calpha(i-1)) correlates strongly with the backbone
      conformation, while only a weak conformational dependence on the size of
      1J(Ni,Calphai) coupling constants was observed. Coupling constants in the
      denatured state of ubiquitin were uniform along the sequence of the protein and
      not dependent on a given residue type. Furthermore it was shown that the observed
      coupling constants were in good agreement with predicted coupling constants using
      a simple model for the random coil.

PMID- 12061718
TI  - Refinement of the solution structure of the heparin-binding domain of vascular
      endothelial growth factor using residual dipolar couplings.
AB  - Previous NMR structural studies of the heparin-binding domain of vascular
      endothelial growth factor (VEGF165) revealed a novel fold comprising two
      subdomains, each containing two disulfide bridges and a short two-stranded
      antiparallel beta-sheet. The mutual orientation of the two subdomains was poorly
      defined by the NMR data. Heteronuclear relaxation data suggested that this
      disorder resulted from a relative lack of experimental restraints due to the
      limited size of the interface, rather than inherent high-frequency flexibility.
      Refinement of the structure using 1H(N-15N residual dipolar coupling restraints
      results in significantly improved definition of the relative subdomain
      orientations.

PMID- 12061720
TI  - Sequential NMR assignment of the ferri-cytochrome c3 from Desulfovibrio vulgaris
      Hildenborough.

PMID- 12061719
TI  - Protein dynamics in supercooled water: the search for slow motional modes.
AB  - The impact of studying protein dynamics in supercooled water for identifying slow
      motional modes on the micros time scale is demonstrated. Backbone 15N spin
      relaxation parameters were measured at -13 degrees C for ubiquitin, which plays a
      central role for signaling proteolysis, cellular trafficking and kinase
      activation in eukaryotic organisms. A hitherto undetected motional mode involving
      Val 70 was found, which may well play an important role for ubiquitin
      recognition. The measurement of rotating frame 15N relaxation times as a function
      of the spin-lock field allowed determination of the correlation time of this
      motional mode, which would not have been feasible above 0 degrees C.

PMID- 12061721
TI  - Assignment of the 1H, 13C, and 15N signals of Synechocystis sp. PCC 6803
      methemoglobin.

PMID- 12061722
TI  - 1H, 13C, 15N NMR sequence-specific resonance assignment of a Clostridium
      thermocellum type II cohesin module.

PMID- 12061723
TI  - 1H, 15N and 13C assignments of the targeting (FAT) domain of focal adhesion
      kinase.

PMID- 12061724
TI  - Assignment of backbone 1H, 13C, and 15N resonances of human Grb7-SH2 domain in
      complex with a phosphorylated peptide ligand.

PMID- 12061725
TI  - Isolation of novel differentially expressed genes related to human glioma using
      cDNA microarray and characterizations of two novel full-length genes.
AB  - Identification of the genes that are differentially expressed between brain tumor
      and normal brain tissues is important for understanding the molecular basis of
      these nerve system tumors and for defining possible targets for therapeutic
      intervention. This investigation is intended to obtain differentially expressed
      genes related to human glioma using cDNA microarray. Total RNA was extracted from
      human glioma specimens and normal brain tissues, and mRNA was obtained by
      oligotex chromatography. The cDNA microarray contains 4366 novel cDNA clones. The
      results of hybridization were scanned using computer system. Two genes selected
      from the results of cDNA microarray hybridization were subsequently analyzed by
      bio-informatic approach, Northern blot, in situ hybridization and radiation
      hybridization. We demonstrated that at a differentially expressed ration of two
      to three times, 15 cDNA clones were considered differentially expressed. Two
      novel full-length genes were selected for further investigation, one named human
      PKIbeta gene (clone 436F11, GenBank with accession number: AF225513) was over
      expressed in normal brain tissues and the other named human ribosomal protein
      L14.22 gene (clone 507E08, GenBank with accession number: AF329277) was over
      expressed in gliomas. Furthermore, the 436F11 gene was located on 6q21-q23
      between the D6S304 and D6S2156 markers, while the 507E08 gene was located between
      the D14S1066 and D14S265 markers. We realized that cDNA microarray technology can
      be successfully applied to identify differentially expressed genes in human
      glioma. This approach is superior to routine representational difference
      analysis, suppression subtractive hybridization and Northern blot for detection
      and isolation of differentially expressed genes in different tissues. At present,
      we have discovered two novel full-length genes related to human glioma and their
      characterizations have been partially clarified.

PMID- 12061726
TI  - Polymer delivery of camptothecin against 9L gliosarcoma: release, distribution,
      and efficacy.
AB  - Camptothecin is a potent antineoplastic agent that has shown efficacy against
      multiple tumor lines in vitro; unfortunately, systemic toxicity has limited its
      in vivo efficacy. This is the first study to investigate the release,
      biodistribution, and efficacy of camptothecin from a biodegradable polyanhydride
      polymer. Tritiated camptothecin was incorporated into biodegradable polymers that
      were implanted intracranially in 16 male Fischer 344 rats and the animals were
      followed up to 21 days post-implant. A concentration of 11-45 microg of
      camptothecin-sodium/mg brain tissue was within a 3 mm radius of the polymer disc,
      with levels of 0.1 microg at the outermost margin of the rat brain, 7 mm from the
      site of implantation. These tissue concentrations are within the therapeutic
      ranges for human and rat glioma lines tested against camptothecin-sodium in
      vitro. The in vivo efficacy of camptothecin-sodium was evaluated with male
      Fischer 344 rats implanted intracranially with 9L gliosarcoma and compared with
      the efficacy of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). The animals were
      divided into four groups. Group 1 (control) had a median survival of 17 days.
      Group 2 (3.8% BCNU polymer) had a median survival of 23 days (P = 0.006). Group 3
      (20% camptothecin polymer) had a median survival of 25 days (P = 0.023). Group 4
      (50% camptothecin polymer) had a median survival of 69 days (P < 0.001). Drug
      loadings of 20% and 50% camptothecin released intact camptothecin for up to 1000
      h in vitro. We conclude that the biodegradable polymer p(CPP: SA) releases
      camptothecin-sodium, produces tumoricidal tissue levels, results in little or no
      systemic toxicity, and prolongs survival in a rat glioma model.

PMID- 12061727
TI  - Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant
      neuroectodermal tumor.
AB  - Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a
      wide variety of neoplasms in several preclinical studies, but it showed poor
      efficacy in patients with nervous system tumors. We have carried out an
      experimental study in order to evaluate the effect of CPT-11 on the growth of a
      subcutaneously implanted malignant neuroectodermal tumor, after administration by
      different routes. The results showed that CPT-11 administration by
      intraperitoneal injections (at dose 10 mg/kg, 5 days per week, for 2 weeks,
      followed by 7-days rest period--one course--to a total of two courses) had no
      significant antitumor effect. Nevertheless, continuous infusion by
      intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4
      microg/h) showed a significant delay in tumor growth in 4 weeks of the
      implantation. The best antitumor effects were observed after CPT-11 intratumoral
      administration (at dose of 5 mg/kg, 5 days per week, for 2 weeks, followed by 7
      days rest period, to a total of three courses) reaching tumor regression in the
      treated animals. These results suggest the utility of CPT-11, by means of
      intralesional administration, on malignant tumors of the nervous system.

PMID- 12061728
TI  - Intracarotid RMP-7 enhanced indocyanine green staining of tumors in a rat glioma
      model.
AB  - OBJECTIVE: The extent of resection in patients with primary brain tumors may
      affect the quality of life, time to tumor progression, and survival. Currently,
      the extent of resection during surgery is guided by the visual appearance and
      consistency of tumor, frozen sections of the margins, intraoperative ultrasound,
      and frameless navigational systems and intraoperative imaging modalities. A new
      method that enhances the visualization of an infiltrating tumor and its margins
      may further aid in obtaining a more complete resection. A study was thus
      undertaken to assess the staining of brain tumors using Indocyanine green (ICG),
      a water-soluble emerald green tricarbocynanine dye concomitantly with RMP-7, a
      bradykinin analog, that selectively increases vascular permeability in brain
      tumors. METHODS: A syngeneic ethyl-nitrosourea-induced F-344 rat cell line (36B
      10) was stereotactically implanted into 25 rats, and allowed to mature for 15-18
      days. Intracarotid administration of 0.75 ml of RMP-7 at a standard dose of 0.4
      microg/ml over 15 min was then infused. Varying doses of ICG (range, 0-60 mg/kg)
      were then injected 15 min after the RMP-7 infusion ended. The animals were
      sacrificed 15 min after the ICG infusion was completed, and the brains examined
      macroscopically and microscopically for evidence of tumor staining. RESULTS: This
      study demonstrated consistent staining of the tumor at only slightly lower ICG
      doses than previously described, however uptake at the tumor margins was evident
      at much lower doses. Thus the combination of ICG and RMP-7 administered
      preoperatively may provide visual enhancement of an infiltrating tumor and its
      margins to help facilitate a radical tumor removal.

PMID- 12061730
TI  - Metastatic choroid plexus papilloma: a case report.
AB  - Choroid plexus papillomas (CPPs) are generally regarded as benign tumours, with a
      favourable long-term prognosis. Complete resection should result in cure. We
      present a case of diffuse craniospinal seeding from an apparently completely
      resected fourth ventricular primary tumour. A 51-year-old male is discussed, who
      presented 5 years following complete resection of a CPP from the fourth
      ventricle, with a progressive history of left sided tinnitus, hearing loss,
      impotence and recent low back pain. Imaging demonstrated multiple craniospinal
      lesions explaining his symptomatology. Differential diagnosis lay between long
      standing CSF seeding, malignant transformation in the primary tumour, or
      metastatic spread from an undefined source. He underwent whole body FDG-PET scan
      which demonstrated a single metabolically active lesion in the sacral canal. A
      subtotal excision biopsy of this sacral lesion was performed which was
      indistinguishable histologically from the primary tumour resected from the fourth
      ventricle. Histological and functional imaging characteristics of the primary
      tumour have been unhelpful in predicting its subsequent behaviour. The present
      case illustrates the extremely rare consequences of metastases from this
      histologically benign tumour and adds to the literature on metastatic
      craniospinal disease.

PMID- 12061729
TI  - Effective solitary hyperthermia treatment of malignant glioma using stick type
      CMC-magnetite. In vivo study.
AB  - Various kinds of hyperthermic treatment for malignant glioma had been inhibited
      due to both their incomplete feverish action and strict cooling effect of the
      brain. The author shows an effective results of hyperthermia for the treatment of
      malignant glioma in an in vivo study using stick type carboxymethylcellulose
      (CMC)-magnetite, a newly manufactured magnetite-product. A stick type CMC
      magnetite, containing magnetite particles, was inserted into the T-9 glioma in
      the rat brain stereotactically, and the rats were exposed to an alternative
      magnetic field (AMF). The application time of AMF, which measured 88.9 kHz and
      380 Oe, was 30 min a day. The rats were divided into three groups: three AMF
      applications (group I), one AMF application (group II) and no application but
      only injection of CMC-magnetite (control). As a result, the mean survival in days
      of these three groups measured 44.2+/-10.9 (group I), 17.0+/-1.5 (group II) and
      14.4+/-1.5 (control). This investigation showed both significant effectiveness in
      attacking malignant glioma and significant prolonging of the survival time in
      rats. It is also a characteristic feature of the magnetite particles to spread
      through the tumor diffusely after three applications of AMF. This feature seemed
      to be one of the main factors that caused greater hyperthermic effect on glioma
      in this study. This method of hyperthermic treatment could be a useful strategy
      in the treatment of malignant glioma.

PMID- 12061731
TI  - A case of intramedullary spinal cord tumor producing human chorionic
      gonadotropin.
AB  - We experienced a case of a persistent trophoblastic disease associated with
      gradually progressive Brown-Sequard syndrome, which was found to be due to a
      primary intramedullary spinal cord germinoma with syncytiotrophoblastic giant
      cells (STGC). We performed both chemotherapy and radiotherapy on separate
      occasions. Although the chemotherapy appeared to be ineffective, radiotherapy
      resulted in the disappearance of spinal cord lesions for four years. We reported
      a case of intramedullary spinal cord germinoma with STGC for which radiotherapy
      was a better therapeutic modality.

PMID- 12061732
TI  - Tumors of the central nervous system in Korea: a multicenter study of 3221 cases.
AB  - The Neuropathology Study Group of the Korean Society of Pathologists conducted a
      nationwide collection of central nervous system (CNS) tumors to evaluate the
      relative frequency in Korea of CNS tumors belonging to the revised World Health
      Organization (WHO) classification categories. A total of 3221 histologically
      proven cases of CNS tumors were collected from 13 institutes between 1997 and
      1998. All the cases were classified according to the revised WHO histological
      types and analyzed for the relative frequency, the distribution of age and sex,
      and location of tumors. The most frequent type of CNS tumors in Korea was
      meningiomas, followed by pituitary adenoma, glioblastoma, astrocytoma, and
      schwannoma. Among the pediatric CNS tumors, pilocytic astrocytoma,
      medulloblastoma, craniopharyngioma, germ cell tumors, and ependymomas were common
      types of tumors. Compared with a previous nationwide study, the rates for
      neuronal/glial tumors, glioblastoma, malignant lymphoma, and cystic lesion were
      increased, and the rate of embryonal tumors was decreased. The overall male to
      female ratio was 0.9: 1, which may be attributed to the greater number of female
      predominate meningiomas and pituitary adenoma. Compared with Western countries,
      Koreans had higher rates of pituitary adenoma and meningiomas and lower rate of
      gliomas. The relative frequency of CNS tumors among Koreans is very similar to
      that reported in Taiwan. The occurrence rates for various subtypes of CNS tumors
      in Korea are distinct from those in the United States and Europe and similar in
      many ways to those in Asian and Mexican population.

PMID- 12061733
TI  - Lobular capillary hemangioma of the spinal cord: case report and review of the
      literature.
AB  - Lobular capillary hemangiomas are common, benign, vascular soft-tissue tumors
      located in the head and neck during the childhood and early adulthood. Report of
      these lesions in the central nervous system has been anecdotal. The case of one
      patient treated for spinal cord compression secondary to a capillary hemangioma
      with elevated proliferation index is presented. A review of the published cases
      in the English literature is provided, as well as a discussion on our case
      findings and the management of these lesions in the spinal cord.

PMID- 12061735
TI  - Some tools for molecular imaging.

PMID- 12061734
TI  - Leptomeningeal carcinomatosis after major remission to taxane-based front-line
      therapy in patients with advanced breast cancer.
AB  - AIM: To determine the incidence of leptomeningeal carcinomatosis (LMC), as the
      first manifestation of systemic progression, in breast cancer patients after
      obtaining a major response (complete response, CR or >80% partial response, PR)
      to first-line taxane-based chemotherapy treated between 1996 and 2000 in our
      Medical Oncology Unit. PATIENTS AND METHODS: Patients with histologically proven
      breast cancer having either metastatic disease, or high-risk locoregional disease
      that were entered into treatment protocols with first-line taxane (paclitaxel or
      docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as
      the first evidence of progression after major response (CR or >80% PR) were
      analyzed in the present study (n = 155). RESULTS: Seven patients with a median
      age of 54 (range: 40-70) years developed LMC as their first evidence of
      progression after taxane-based regimens with a median interval of 6 months
      (range: 2-18) from start of treatment to diagnosis of LMC. Five patients received
      intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT),
      while one patient received i.t. methotrexate and RT to lumbar spine. Two patients
      responded to treatment for LMC, while two achieved stable disease and three
      progressed. Two patients had elevated cerebrospinal fluid tumor markers (more
      than serum marker levels) that proved useful in monitoring response to treatment.
      Median survival after LMC was 3.6 months (range: 1-31+) and correlated positively
      to the interval from the initiation of taxane-based therapy to LMC (r = 0.84, P =
      0.019). Seven out of 86 responders (8.1%; 95% confidence interval, 2.4-13.9)
      developed LMC as the first sign of progression after a major response to first
      line chemotherapy. CONCLUSIONS: LMC after a major response to front-line taxane
      based regimens represents a grave disease manifestation and its incidence appears
      increased when compared in retrospect to non-taxane-treated patients. Prospective
      evaluation of the incidence of LMC after taxane versus non-taxane-based treatment
      from large randomized multiinstitutional trials is warranted and identification
      of potential prognostic factors might help identify patients requiring
      appropriate prophylactic therapy.

PMID- 12061738
TI  - Personal computer-based PACS display system: comparison with a dedicated PACS
      workstation for review of computed radiographic images in rheumatoid arthritis.
AB  - RATIONALE AND OBJECTIVES: The authors' purpose was to investigate the reliability
      of a personal computer (PC)-based display system compared with a workstation in
      the evaluation of rheumatoid arthritis on computed radiographs of the hands.
      MATERIALS AND METHODS: Two radiologists on two occasions independently scored
      randomized computed radiographs of individual joints of the hands from 23
      patients with rheumatoid arthritis and 14 control subjects. Each joint was scored
      from 0 (definitely normal) to 30 (severe disease) for each of four variables:
      soft-tissue swelling, osteopenia, erosions, and joint space narrowing. The
      observations were replicated on a picture archiving and communication system
      workstation and a PC. Intraobserver and interobserver reliability were
      calculated, as was the difference in scores between the two systems. The null
      hypothesis was that there was no difference between the workstation and the PC.
      RESULTS: The intraobserver reliability for normal versus abnormal joints was 73%
      with the workstation and 79% with the PC. The intraobserver reliability for
      workstation versus PC was 83%. There was moderate interreader reliability for
      both platforms (average kappa statistic, 0.46 [workstation] vs 0.45 [PC]). Small
      differences in scores between platforms are probably due mostly to the ordinal
      nature of the scoring system. CONCLUSION: For evaluating computed radiographs of
      the hands in early rheumatoid arthritis, a PC-based system provides results
      similar to those obtained with a workstation, at considerably reduced cost.

PMID- 12061737
TI  - Pulmonary nodule detection and visual search: P45 and P104 monochrome versus
      color monitor displays.
AB  - RATIONALE AND OBJECTIVES: The faceplate of a cathode-ray tube (CRT) display
      monitor is covered on the vacuum side with a phosphor screen. The different
      phosphors that can be used for this screen have distinctly different physical
      properties that can affect the noise properties of the display. Differences in
      noise affect the signal-to-noise ratio and, hence, may affect diagnostic
      performance. This study evaluated observer performance and visual search
      parameters in the detection of pulmonary nodules, comparing two monochrome CRT
      monitors with different phosphors (P45 and P104) and a color CRT monitor.
      MATERIALS AND METHODS: The receiver operating characteristic paradigm was used to
      evaluate observer performance with a series of radiographic chest images
      containing solitary pulmonary nodules. Eye position was recorded as the observers
      searched the images on each type of monitor. RESULTS: Observer performance, as
      indicated by the area under the receiver operating characteristic curve and
      compared by means of an analysis of variance test, was best for the P45 monitor,
      next best for the P104 monitor, and worst for the color monitor. All differences
      were statistically significant. Eye-position parameters were also affected by
      monitor type. The time required to fixate the lesion and overall search times
      were longest with the color monitor. CONCLUSION: The type of phosphor used in the
      CRT monitor faceplate can affect diagnostic performance and visual search
      parameters. Care should be taken in the selection of monitors for use in clinical
      radiology.

PMID- 12061736
TI  - CT and radionuclide study of BMP-2 gene therapy-induced bone formation.
AB  - RATIONALE AND OBJECTIVES: Gene therapy techniques have the potential to treat
      numerous diseases, from cancer to diabetes. One promising application is the use
      of bone morphogenetic protein (BMP) gene transfer to induce bone formation.
      Previous studies have demonstrated that both direct and ex vivo BMP gene therapy
      have the capacity to initiate the normal endochondral pathway, leading to rapid
      mature bone formation. In the present study, computed tomography (CT) and
      radionuclide imaging was used to assess bone formation induced by BMP gene
      therapy accurately and noninvasively. MATERIALS AND METHODS: Athymic nude rodents
      were treated with 1.25 x 10(10) particles of adenovirus-BMP-2 (Ad-BMP-2)
      (treatment group) or adenovirus-beta-gal (control group). At various intervals
      after treatment, the animals underwent CT, planar digital radiography, and planar
      radionuclide scintigraphic imaging. RESULTS: Radionuclide scintigraphy clearly
      demonstrated active bone deposition that began as early as 15 days after
      treatment and peaked at approximately 36 days, only at the Ad-BMP-2 injection
      sites. CT clearly demonstrated ectopic bone induction over time at the Ad-BMP-2
      treatment sites, in perfect correlation with the scintigraphic findings.
      CONCLUSION: This study clearly illustrates that gene therapy-induced osteogenesis
      can be studied with multimodality imaging and supports the use of these
      approaches in future preclinical and clinical studies.

PMID- 12061739
TI  - Causes of interscan variability of coronary artery calcium measurements at
      electron-beam CT.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to investigate the
      causes of interscan variability of coronary artery calcium measurements at
      electron-beam computed tomography (CT). MATERIALS AND METHODS: Two sets of
      electron-beam CT scans were obtained in 298 consecutive patients who underwent
      electron-beam CT to screen for coronary artery calcium. Interscan variations of
      coronary artery calcium characteristics and the effects of heart rate,
      electrocardiographic (ECG) triggering method, image noise, and coronary motion on
      interscan variability were analyzed. RESULTS: The interscan mean variabilities
      were 21.6% (median, 11.7%) and 17.8% (median, 10.8%) with the Agatston and
      volumetric score, respectively (P < .01). Variability decreased with increasing
      calcification score (34.6% for a score of 11-50 and 9.4% for a score of 400
      1,000, P < .0001). The absolute difference in Agatston score between scans was
      44.1 +/- 95.6. The correlation coefficient between the first and second sets of
      scans was 0.99 (P < .0001). Lower interscan variability was found in younger
      patients (<60 years), patients with stable heart rates (heart rate changing less
      than 10 beats per minute during scanning), patients with no visible coronary
      motion, and those with an optimal ECG triggering method (P < .05 for all).
      Results of multivariate logistic analysis showed that changes in calcium volume,
      mean attenuation, and peak attenuation were significant predictors of interscan
      variability and caused the interscan variations of the coronary artery calcium
      measurements (r2 = 0.83, P < .0001). CONCLUSION: Coronary calcification at
      electron-beam CT varies from scan to scan. Volumetric scoring and optimal ECG
      triggering should be used to reduce interscan variability. Baseline calcium score
      and interscan variability must be considered in the evaluation of calcium
      progression.

PMID- 12061740
TI  - Evidence-based radiology: requirements for electronic access.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to determine the
      electronic requirements for supporting evidence-based radiology in today's
      medical environment. MATERIALS AND METHODS: A software engineering technique, use
      case modeling, was performed for several clinical settings to determine the use
      of imaging and its role in evidence-based practice, with particular attention to
      issues relating to data access and the usage of clinical information. From this
      basic understanding, the analysis was extended to encompass evidence-based
      radiologic research and teaching. RESULTS: The analysis showed that a system
      supporting evidence-based radiology must (a) provide a single point of access to
      multiple clinical data sources so that patient data can be readily used and
      incorporated into comprehensive radiologic consults and (b) provide quick access
      to external evidence in the way of similar patient cases and published medical
      literature, thus supporting evidence-based practice. CONCLUSION: Information
      infrastructures that aim to support evidence-based radiology not only must
      address issues related to the integration of clinical data from heterogeneous
      databases, but must facilitate access and filtering of patient data in order to
      improve radiologic consultation.

PMID- 12061741
TI  - DataServer: an infrastructure to support evidence-based radiology.
AB  - Following a requirements analysis for development of an information
      infrastructure supporting evidence-based radiology, the objective of this study
      was the development of a data gateway to support flexible access to the totality
      of a patient's electronic medical records through a single, uniform
      representation, regardless of the underlying data sources (eg, hospital
      information systems [HIS], radiology information systems [RIS], picture archiving
      and communication systems [PACS]). XML-based (eXtensible Markup Language)
      technologies were employed to create an application framework permitting querying
      of different clinical databases. The contents of different data sources were
      represented by using XML. On the basis of these representations, users can
      specify queries. The system transforms the XML queries into a query format
      understood by the specific databases, processes the query, and transforms the
      results back into an XML format. XML results can then be transformed in
      accordance to different data-formatting standards. Access to several different
      data sources, including HIS, RIS, and PACS, has been accomplished with this
      framework. The extensible nature of the XML data gateway enables data sources to
      be readily added. The framework also provides a means by which data can be
      systematically de-identified to protect patient confidentiality, thus supporting
      research endeavors.

PMID- 12061742
TI  - Gadolinium-enhanced T1-weighted renal and abdominal MR imaging: quantitative
      discrepancy between clinical and in vitro findings.
AB  - RATIONALE AND OBJECTIVES: This study was conducted to compare the magnetic
      resonance (MR) contrast medium enhancement of abdominal organs in vivo with the
      signal intensity (SI) values of known in vitro gadolinium solutions. MATERIALS
      AND METHODS: A phantom was imaged with the MR contrast medium gadodiamide
      (Omniscan; Nycomed, Princeton, NJ) of solutions at full-strength (0.5 mmol/mL),
      one-third, 1/10, and 1/100 concentrations. A fat-suppressed fast spoiled gradient
      echo pulse sequence with flip angles ranging from 10 degrees to 170 degrees (at
      20 degrees increments) was performed with a 1.5-T magnet. In 12 subjects, the SIs
      of abdominal organs were determined with identical imaging parameters, before and
      after administration of gadodiamide injection at 0.1 mmol/kg. RESULTS: As
      anticipated, the plot of SI in relation to gadodiamide concentration is
      nonlinear, with a decrease in SI due to T2 effects at concentrations above 0.05
      mmol/mL. The kidney showed the highest SI after gadodiamide enhancement (125.2 +/
      11.6 [standard error] at 2.5 minutes), followed by the liver (76.5 +/- 11.5 at 1
      minute) and spleen (57.26 +/- 9.35 at 30 seconds). The SI of the renal medulla
      (114.2 +/- 9.8 at 4.5 minutes) was approximately one-third that in phantom
      observations. CONCLUSION: The authors observed a marked discrepancy between
      empirical contrast medium performance in abdominal organs and SI values for
      comparable gadodiamide concentrations in vitro. One possible reason is the
      intracellular compartmentalization of water molecules in vivo. These results
      suggest a need for a better understanding of MR contrast medium performance in
      vivo.

PMID- 12061744
TI  - Time for change: new emphasis on training for radiology research.

PMID- 12061743
TI  - Prediction of treatment response of head and neck cancers with P-31 MR
      spectroscopy from pretreatment relative phosphomonoester levels.
AB  - RATIONALE AND OBJECTIVES: Combinations of chemotherapy and fractionated radiation
      therapy are the currently preferred nonsurgical treatment methods for squamous
      cell carcinoma of the head and neck, but to the authors' knowledge there is no
      reliable marker for predicting therapeutic response. Early identification of
      nonresponders would allow prompt replacement of ineffective, toxic therapy by
      alternative, potentially more effective procedures. Frequent regional node
      involvement facilitates surface coil investigation with phosphorus-31 magnetic
      resonance spectroscopy. MATERIALS AND METHODS: P-31 magnetic resonance spectra
      were acquired from 12 patients before radiation therapy or chemotherapy. In vivo
      three-dimensional localized P-31 nuclear magnetic resonance chemical shift
      imaging was performed with a 1.5-T clinical imager and a dual-tuned H-1/P-31
      surface coil. Proton decoupling and nuclear Overhauser enhancement were used to
      improve sensitivity and resolve overlapping signals in the phosphomonoester
      region of the spectrum. RESULTS: The average pretreatment ratio of
      phosphomonoester to beta-nucleoside triphosphate was significantly smaller in
      complete responders (n = 4) than in incomplete responders (partial responders
      plus nonresponders, n = 8) (0.0 +/- 0.0 vs 1.22 +/- 0.17 [P = .004]). CONCLUSION:
      Results of this preliminary study suggest that H-1-decoupled P-31 magnetic
      resonance spectroscopy may prove to be a useful predictor of therapeutic response
      in head and neck cancers.

PMID- 12061745
TI  - National Institutes of Health Extramural Loan Repayment Program.

PMID- 12061746
TI  - Distributed Web-supported radiology clerkship for the required clinical clerkship
      year of medical school: development, implementation, and evaluation.
AB  - RATIONALE AND OBJECTIVES: The authors performed this study to develop, implement,
      and evaluate a new radiology clerkship for the required clinical clerkship year
      of medical school. MATERIALS AND METHODS: A mandatory radiology clerkship
      experience was added to the required clinical clerkships as a series of 10
      independent half-day teaching sessions. These sessions were distributed as one
      session per existing clerkship throughout the year. To provide continuity and
      organization, Web-based curriculum materials were designed and implemented as a
      component of the radiology clerkship. The new clerkship was evaluated with
      observations, pretest and posttest measures with a control group, structured and
      unstructured student and faculty surveys, and individual and small group
      interviews. RESULTS: The clerkship was successfully developed and implemented.
      Ninety-five students have completed the clerkship. Their mean posttest score
      (84.8) was significantly higher than their mean pretest score (58.8, P < .001)
      and the mean control group score (59.7, P < .001). Students rarely used the Web
      site. Disadvantages of the distributed clerkship were identified. CONCLUSION: A
      radiology clerkship distributed among existing clerkships is feasible but has
      many disadvantages. Students greatly prefer live instruction, and Web-based
      educational materials are more valuable to faculty and administrators than to
      students.

PMID- 12061747
TI  - General competencies in radiology residency training: definitions, skills,
      education and assessment.

PMID- 12061748
TI  - Research training in imaging at the NIH.

PMID- 12061749
TI  - Working memory, intelligence and knowledge base in adult persons with
      intellectual disability.
AB  - Previous studies have suggested that performance in working memory (WM) tasks is
      deficient in all etiologies and at all levels of intellectual disability (ID).
      Knowledge about WM structure, cognitive processes reflected in WM tasks, or the
      long-term memory contribution to WM capacity in ID is. however, not satisfactory.
      In the present study, WM capacity, WM task requirements, as well as effects
      between WM, skills, knowledge base, and intelligence were explored in two groups
      with matched fluid intelligence: adult persons with ID and normally developing
      children aged 3-6 years. The ID Group performed equally well as the children in
      WM tasks based on familiar semantic information and were significantly better on
      all measures reflecting skills and knowledge base. The Child Group performed
      better in phonological and visuo-spatial WM tasks including nonsemantic
      information, respectively. In particular, it appeared that the groups differed in
      their WM performance although they were matched for fluid intelligence. We
      hypothesize that the ID Group depended more on knowledge support from long-terrm
      memory whereas the Child Group could benefit more from efficient online WM
      processes.

PMID- 12061750
TI  - Four-year follow-up of children with low intelligence and ADHD: a replication.
AB  - Twenty children with attention deficit hyperactivity disorder (ADHD) and low IQs,
      who participated in a drug study, were followed up 4.5 years later, when their
      ages averaged 12.4 years (range: 8-20 years: SD = 2.78). Participants were
      assessed by their parents and teachers on the Aberrant Behavior Checklist
      Community (ABC; Aman & Singh, 1994), on the Child Symptom Inventory (CSI; Gadow &
      Sprafkin, 1994), and on a structured interview. A majority of children continued
      to screen positive for ADHD at follow-up, as well as display high rates of
      comorbid anxiety disorders, tics, and elimination disorders. Educational
      placement became slightly more restrictive over the follow-up interval. Multiple
      medication trials (30 in all, among 14 participants) were attempted between
      initial contact and follow-up. Ratings on the ABC by parents and teachers showed
      significantly lower scores at follow-up on the Hyperactivity subscale. Relatively
      few associations were found between initial ratings and follow-up ratings on
      standardized scales.

PMID- 12061751
TI  - Do adults with mental retardation show pictorial superiority effects in recall
      and recognition?
AB  - We examined memory for pictures and words in adults with mental retardation and a
      control group of adults of normal intelligence. During acquisition, sets of
      simple line drawings and matching words were presented for study using an
      intentional learning procedure. The principle dependent measures were free recall
      and recognition. Measures of working memory span were also administered.
      Pictorial superiority effects occurred in free recall and recognition for both
      intelligence-level groups. Correlational analyses indicated that working memory
      span was primarily related to recall performance, irrespective of stimulus
      format. These data strongly suggest that persons with mental retardation can
      utilize nonverbal memory codes to support long-term retention as effectively as
      do adults of normal intelligence.

PMID- 12061752
TI  - Impact of stimulation versus microswitch-based programs on indices of happiness
      of people with profound multiple disabilities.
AB  - This study was designed to assess whether the impact of a microswitch-based
      program on indices of happiness would be comparable with that of a stimulation
      program. Three persons with profound multiple disabilities participated. The
      microswitch-based program produced increases in indices of happiness which were
      fairly clear for the first two participants and quite modest for the third
      participant. These data were largely comparable with those obtained with the
      stimulation program. Implications of the findings in terms of program
      practicality, participants' independence and environmental control are discussed.

PMID- 12061753
TI  - Multiple factors in the long-term effectiveness of contingent electric shock
      treatment for self-injurious behavior: a case example.
AB  - This report describes the effective treatment of self-injurious behavior (SIB)
      using contingent electric shock in an adolescent. Data are presented to document
      the initial dramatic reduction in SIB and the ongoing effectiveness of the
      treatment over a 5-year period. Positive side effects of the intervention are
      documented, as is information on the interaction of a medical condition (e.g.,
      ear infections, fever), psychoactive medication status, and staff changes that
      served to effect the rate of SIB across 4 years of treatment. Recognizing and
      attending to these various factors has served to insure the success of the
      aversive intervention with very low rates of SIB and, consequently, very low
      rates of the administration of electric shock. Keeping the rate of administration
      of shock low serves to decrease the chances of habituation to the shock thereby
      emphasizing the importance of attending to the individual's total medical,
      social, and administrative environments.

PMID- 12061754
TI  - Multiple attention systems in perceptual categorization.
AB  - Five observers categorized inverted L-shaped stimuli according to the length of
      the horizontal line segment. A centrally located spatial cue preceded the
      stimulus on each trial. On 80% of the trials, the (relevant) horizontal line
      segment fell within the cued location, and on 20% of the trials the (irrelevant)
      vertical line segment fell within the cued location. The empirical results
      provide support for the hypothesis that perceptual attention can focus on the
      stimulus attribute inside the spatially cued location at the same time that
      decisional attention is focused on the (relevant) horizontal attribute--that is,
      the results suggest that perceptual and decisional attention can function
      independently during categorization. Decision bound models and extended
      generalized context models that assume separate perceptual and decisional
      attention systems were fitted to the data. Versions of the models that assume
      that the spatial cue affected perceptual attention were superior to versions that
      assume no effect on perceptual attention. These theoretical analyses support the
      functional independence hypothesis and suggest that formal theories of
      categorization should model the effects of perceptual and decisional attention
      separately.

PMID- 12061755
TI  - Essentialist to some degree: beliefs about the structure of natural kind
      categories.
AB  - Previous research has provided conflicting evidence regarding the hypothesis that
      people are essentialists. Much of the evidence in favor of essentialism is based
      on demonstrating that categories are thought to have absolute membership.
      Although the hypothesis is often framed as an absolute claim about all categories
      of a certain type (e.g., natural kinds), it has generally been tested by making
      relative comparisons with a select sample. The present study assesses judgments
      of absolute structure across a range of categories. A further condition for
      essentialism is that the criteria for category identity be seen as objective
      rather than conventional. The results of three experiments based on these
      considerations do not provide support for essentialist claims. Few categories
      were judged to have essentialist structure, in terms of either absolute
      membership or objective criteria. Results are discussed in light of an
      alternative to the essentialist hypothesis that emphasizes a pragmatic view of
      categories.

PMID- 12061756
TI  - The effect of category learning on sensitivity to within-category correlations.
AB  - A salient property of many categories is that they are not just sets of
      independent features but consist of clusters of correlated features. Although
      there is much evidence that people are sensitive to between-categories
      correlations, the evidence about within-category correlations is mixed. Two
      experiments tested whether the disparities might be due to different learning and
      test tasks. Subjects learned about categories either by classifying items or by
      inferring missing features of items. Their knowledge of the correlations was
      measured with classification, prediction, typicality, and production tests. The
      inference learners, but not the classification learners, showed sensitivity to
      the correlations, although different tests were differentially sensitive. These
      results reconcile some earlier disparities and provide a more complete
      understanding of people's sensitivities to within-category correlations.

PMID- 12061757
TI  - Visual imagery can impede reasoning.
AB  - Although it is natural to suppose that visual mental imagery is important in
      human deductive reasoning, the evidence is equivocal. This article argues that
      reasoning studies have not distinguished between ease of visualization and ease
      of constructing spatial models. Rating studies show that these factors can be
      separated. Their results yielded four sorts of relations: (1) visuospatial
      relations that are easy to envisage visually and spatially, (2) visual relations
      that are easy to envisage visually but hard to envisage spatially, (3) spatial
      relations that are hard to envisage visually but easy to envisage spatially, and
      (4) control relations that are hard to envisage both visually and spatially.
      Three experiments showed that visual relations slow down the process of reasoning
      in comparison with control relations, whereas visuospatial and spatial relations
      yield inferences comparable with those of control relations. We conclude that
      irrelevant visual detail can be a nuisance in reasoning and can impede the
      process.

PMID- 12061758
TI  - Mental simulation inflates performance estimates for physical abilities.
AB  - In five experiments, we examined how mental simulation of physical activities
      affected estimates of one's ability to perform the same activities. In Experiment
      1, participants who simulated lifting aheavy object estimated that they could
      lift more weight than did participants who did not perform the simulation. In
      Experiment 2A, the frequency with which participants performed the simulation
      exercises was manipulated. In Experiments 2B and 2C, we manipulated the amount of
      weight that people simulated lifting in order to address potential alternative
      explanations of the inflation effect. In Experiment 3, mental simulations were
      manipulated within subjects. In all the experiments, the simulated events showed
      inflated estimates, as compared with nonsimulated events. These results were
      interpreted in the context of the misattribution-of-familiarity account of
      imagination inflation.

PMID- 12061759
TI  - Experiencing a word can prime its accessibility and its associative connections
      to related words.
AB  - This paper reports the results of manipulations of word features for the
      magnitude of priming effects. In Experiment 1, the printed frequency of the
      target words and the number of connections among their associates were varied,
      and during testing participants were given cues and asked to produce the first
      word to come to mind as rapidly as possible in implicit free association. Priming
      effects were greater for low-frequency words and for those with many connections
      among their associates. In Experiments 2 and 3, target words were presented under
      incidental or intentional learning conditions during study, and the presence of
      direct preexisting connections from target to cue and from cue to target was
      varied. Priming effects were greater when either connection was present, with
      each connection having additive effects. In Experiments 4 and 5, priming effects
      for indirect links (shared associates and mediators) were examined. The results
      of these experiments indicate that priming in free association depends on both
      the general accessibility of the target as a response and the strengthening of
      direct target-to-cue connections. These findings raise problems for theories that
      attribute priming only to target accessibility or only to target-to-cue
      association.

PMID- 12061760
TI  - Bias effects in facilitatory phonological priming.
AB  - In four experiments, we examined the facilitation that occurs when spoken-word
      targets rhyme with preceding spoken primes. In Experiment 1, listeners' lexical
      decisions were faster to words following rhyming words (e.g., ramp-LAMP) than to
      words following unrelated primes (e.g., pink-LAMP). No facilitation was observed
      for nonword targets. Targets that almost rhymed with their primes (foils; e.g.,
      bulk-SULSH) were included in Experiment 2; facilitation for rhyming targets was
      severely attenuated. Experiments 3 and 4 were single-word shadowing variants of
      the earlier experiments. There was facilitation for both rhyming words and
      nonwords; the presence of foils had no significant influence on the priming
      effect. A major component of the facilitation in lexical decision appears to be
      strategic: listeners are biased to say "yes" to targets that rhyme with their
      primes, unless foils discourage this strategy. The nonstrategic component of
      phonological facilitation may reflect speech perception processes that operate
      prior to lexical access.

PMID- 12061761
TI  - Adapting a memory framework (source monitoring) to the study of closure
      processes.
AB  - The present experiments adapt a memory framework (source monitoring) to the study
      of closure processes. Closure processes are invoked as explanatory mechanisms
      underlying the ability to identify objects under conditions of incomplete visual
      information. If closure processes are activated, filling in missing pieces of
      visual information, intriguing memory predictions follow. When making source
      judgments about the way in which visual information was experienced initially
      (e.g., complete or incomplete in form), a particular kind of memory error should
      be evident. Incomplete visual information should be remembered as complete in
      form, and indeed, this error is observed. The present experiments test
      alternative interpretations for the initial reports of this memory error in the
      context of a search task modeled after the Where's Waldo? children's books. The
      effects of several new factors (e.g., familiarity) are reported, and alternative
      interpretations for the bias to report complete are eliminated. Findings,
      therefore, have implications for understanding the mechanisms of closure
      processes, as well as for the source-monitoring framework itself.

PMID- 12061762
TI  - Creating bizarre false memories through imagination.
AB  - The present study explored memory for familiar or usual actions (e.g., flip the
      coin) and bizarre or unusual actions (e.g., sit on the dice). In Session 1,
      action statements were presented to 210 participants, who had to either perform
      or imagine those actions. In Session 2, 24 h later, participants imagined
      performing various actions, some presented in the first session and others
      totally new. Finally, in Session 3, 2 weeks later, participants were tested on
      their memory for the original actions. We found that as the number of imaginings
      increased in Session 2, so did the proportion of did responses to actions that
      were only imagined or not even presented. This pattern was present for both
      bizarre and familiar actions. These results demonstrate that bizarre actions may
      lose the item distinctiveness that is used to make accurate memory decisions
      after repeated imagination.

PMID- 12061763
TI  - Increasing confidence in remote autobiographical memory and general knowledge:
      extensions of the revelation effect.
AB  - In recognition tests, items presented in unusual ways (e.g., degraded, revealed
      in stages, or presented as anagrams) are often judged to be old more than are
      intact items. This revelation effect has been observed only in episodic judgments
      about the occurrence or frequency of relatively recent events. The present work
      extends the boundary conditions of this effect. In three experiments, subjects
      unscrambled anagrams in the context of answering questions about their childhood
      (e.g., broke a dwniwo playing ball) or while answering questions pertaining to
      world knowledge (e.g.,fastest animal-elpraod). In each case, a revelation effect
      was observed: Solving an anagram increased confidence in remote autobiographical
      memories and in memory for world facts. These results contradict claims that the
      effect is an episodic memory phenomenon and challenge existing explanations of
      the revelation effect.

PMID- 12061764
TI  - Are inferences from stereotyped role names to characters' gender made
      elaboratively?
AB  - Two experiments provided evidence that gender stereotype inferences from role
      names--for example, that a surgeon is (probably) male--are made in a forward,
      elaborative, direction. We used sentences in which a person's gender was never
      made explicit, but was implied in two different ways. The two ways were by the
      use of a role name, and by mentioning an item of clothing (e.g., a bikini) or a
      biological characteristic (e.g., giving birth) that is typically associated with
      females or males. The two pieces of information (role name and
      clothing/biological characteristic) were presented in different orders in the two
      experiments. In both cases a mismatch between the associated genders slowed
      reading, showing that gender information has been activated. It is argued that if
      an inference about gender is made on the basis of the second piece of
      information, hence slowing comprehension, it is unlikely that the inference about
      gender based on the first piece of information was not made immediately.

PMID- 12061766
TI  - Alignable and nonalignable differences in causal explanations.
AB  - Prior research indicates that people may base their causal explanations on
      distinctive features between an event and a contrasting background instance in
      which the event did not occur. Research on similarity judgments suggests that
      there are two types of distinctive features: alignable differences, which are
      corresponding characteristics of a pair, and nonalignable differences, which are
      characteristics of one item for which there are no corresponding characteristics
      in the other. In three experiments, the hypothesis that people's evaluations of
      causal explanations vary as a function of feature alignment was examined. The
      results suggest that people will rate explanations differently on the basis of
      alignable or nonalignable differences, depending on the type of the event, and
      that alignability depends on the relational structure among the features of the
      event.

PMID- 12061765
TI  - Counting on working memory in simple arithmetic when counting is used for problem
      solving.
AB  - A concurrent-task methodology was used to investigate relations between the
      availability of aspects of working memory resources and both strategy selection
      and execution while simple addition equations (e.g., 4 + 3 = 8) were being
      verified. Consistent with prior research in which production trials have been
      used, undergraduates selected a variety of procedures other than retrieval.
      Availability of working memory resources did not generally affect strategy
      selection. Disrupting central executive and phonological aspects of memory
      affected strategy execution, but only when min counting was used to solve the
      problems. These and other features of the results suggest that availability of
      working memory resources does not contribute to individual differences in
      strategy selection and time to execute retrieval processes.

PMID- 12061767
TI  - Likelihood judgment based on previously observed outcomes: the alternative
      outcomes effect in a learning paradigm.
AB  - Previous research has demonstrated that intuitive perceptions of certainty
      regarding a focal outcome are sensitive to variations in how evidence supporting
      nonfocal alternatives is distributed, even when such variations have no bearing
      on objective probability. We investigated this alternative-outcomes effect in a
      learning paradigm in which participants made likelihood judgments on the basis of
      their memory for past observations of relevant outcomes. In Experiment 1, a
      manipulation of evidence (observed frequencies) across alternative outcomes
      influenced not only intuitive certainty estimates about a focal outcome but also
      numeric subjective probabilities. Experiment 2 ruled out the possibility that
      these effects were attributable to the influence of information loss on frequency
      estimations. The findings were consistent with the heuristic comparison account,
      which suggests that the judged likelihood of a focal outcome will be
      disproportionately influenced by the strength (frequency) of the strongest
      alternative outcome.

PMID- 12061768
TI  - The irrelevant-speech effect and children: theoretical implications of
      developmental change.
AB  - The irrelevant-speech effect refers to the finding of impaired recall performance
      in the presence of irrelevant auditory stimuli. Two broad classes of theories
      exist for the effect, both allowing automatic entry of the distracting sounds
      into the processing system but differing in how attention is involved. As one
      source of evidence in the discussion of existing theories of the irrelevant
      speech effect, the performance of children and adults on a visual serial recall
      task with irrelevant sounds (speech and tones) was examined. The magnitude of the
      effects of irrelevant sounds on performance decreased with age. The developmental
      differences were marked in the conditions with the greatest need for attentional
      control (words and especially changing words). The findings were interpreted with
      respect to current models of memory. Theories of the irrelevant-speech effect
      that include a role for attentional control were better suited to handle the
      results than those without a specified role for attention.

PMID- 12061769
TI  - Hormonal induction of hepatic mitochondrial ornithine/citrulline transporter
      mRNA.
AB  - The urea cycle, which involves enzymes located in both the mitochondrion and
      cytoplasm, requires transport of ornithine and citrulline across the
      mitochondrial membrane by the ornithine/citrulline antiporter ORNT1. Expression
      of the urea cycle enzymes can change dramatically in response to hormones, but it
      is not known whether ORNT1 expression also is hormonally regulated. This study
      therefore tested the hypothesis that ORNT1 mRNA levels in hepatocytes are induced
      by cAMP and glucocorticoid as are the urea cycle enzyme mRNAs. ORNT1 mRNA was
      rapidly induced by a cAMP analog and dexamethasone in cultured rat hepatocytes
      and there was a strong synergistic response to a combination of these agents.
      Ongoing protein synthesis was required for induction of ORNT1 mRNA by
      dexamethasone but not by cAMP, suggesting that the dexamethasone response
      required an accessory factor. Thus, hormonal regulation of ORNT1 mRNA in
      hepatocytes is coordinated with that of mRNAs encoding the urea cycle enzymes.

PMID- 12061770
TI  - Suppression of inducible nitric oxide synthase and tumor necrosis factor-alpha
      expression by 4-nonylphenol in macrophages.
AB  - 4-Nonylphenol (NP) is reported to have estrogenic activity; however, its
      influence on cytokine production or immune system function remains unclear. In
      this study we investigated the effects of NP on the production of nitric oxide
      (NO) and tumor necrosis factor-alpha (TNF-alpha), and on the level of inducible
      nitric oxide synthase (iNOS) and TNF-alpha gene expression in mouse macrophages.
      NP alone did not affect NO or TNF-alpha production. In contrast, NP inhibited
      lipopolysaccharide (LPS)-induced NO and TNF-alpha production, and the levels of
      iNOS and TNF-alpha mRNA in a dose-dependent manner. Treatment with ICI 182.780,
      an estrogen-receptor antagonist, inhibited the suppressive effects of NP. NF
      kappaB sites have been identified in the promoter of the iNOS and TNF-alpha
      genes. Transient expression and electrophoretic mobility shift assays with NF
      kappaB binding sites revealed that NP reduced the levels of the LPS-induced NF
      kappaB transcription factor complex. These results demonstrate that NP may affect
      the regulation of the immune system function by reducing NO and TNF-alpha
      production via the inhibition of NF-kappaB transactivation mediated through the
      estradiol receptor.

PMID- 12061771
TI  - Novel proteinaceous toxins from the nematocyst venom of the Okinawan sea anemone
      Phyllodiscus semoni Kwietniewski.
AB  - The Okinawan sea anemone Phyllodiscus semoni is known to cause cases of severe
      stinging. We isolated P. semoni toxins 60A and 60B (PsTX-60A and PsTX-60B; ca. 60
      kDa) as the major toxins from the isolated nematocysts of this species for the
      first time. PsTX-60A and PsTX-60B showed lethal toxicity to the shrimp Palaemon
      paucidence when administered via intraperitoneal injection (LD(50) values: 800
      900 and 800 microg/kg, respectively) and hemolytic activity toward a 0.8%
      suspension of sheep red blood cells (ED(50) values: 600 and 300 ng/ml,
      respectively). Furthermore, we sequenced the cDNA encoding PsTX-60A. The deduced
      amino acid sequence of PsTX-60A did not show any similarity to previously
      reported proteins. The N-terminal amino acid sequence of PsTX-60B showed homology
      with that of PsTX-60A. These toxins represent a novel class of cytolytic
      proteinaceous toxins.

PMID- 12061773
TI  - Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a
      topological analysis using its deletion mutants.
AB  - LAP1s (lamina-associated polypeptide 1s) are type 2 integral membrane proteins
      with a single membrane-spanning region of the inner nuclear membrane. We report
      here on the cloning of the full-length cDNA of human LAP1B (huLAP1B) that encodes
      584 amino acids. The sequence homology between the predicted rat LAP1B and
      huLAP1B was found to be 73.6%. A topological analysis was carried out by
      transiently expressing N-terminal GFP fused deletion mutants of huLAP1B in cells.
      The transmembrane (TM) domain (aa 346-368) is required for the localization of
      the nuclear and endoplasmic reticulum membrane and that the TM domain and the C
      terminal half of the nucleoplasmic domain (aa 190-331) are sufficient for the
      proper localization of LAP1B. In contrast, the well-conserved lumenal domain of
      the nuclear membrane is not required for its topological function. Biochemical
      analysis showed that huLAP1B is retained within the nucleus via interactions of
      the nucleoplasmic portion with nuclear components.

PMID- 12061772
TI  - Pigment epithelium-derived factor exerts opposite effects on endothelial cells of
      different phenotypes.
AB  - The anti-angiogenic activity of pigment epithelium-derived factor (PEDF) has
      recently been discovered on the basis of its inhibition of ischemia-induced
      retinal neovascularization in an animal model of retinopathy of the premature.
      Moreover PEDF inhibits the migration and proliferation of various endothelial
      cells maintained in culture with FGF(2). Since vascular endothelial growth factor
      (VEGF) is the main angiogenic factor expressed in hypervascularized retinas, we
      investigated the functions of PEDF on retinal endothelial cells whose angiogenic
      phenotype is controlled or not by long term exposure to VEGF as observed in human
      pathologies such as diabetic retinopathy. Here, we observed that PEDF exerts
      opposite effects on endothelial cells depending on their phenotype. We determined
      that when PEDF inhibits endothelial cell growth, it inhibits VEGF-induced MAPK
      activation. However, in endothelial cells cultured with VEGF, PEDF has a
      synergistic action on cell proliferation with VEGF, and this corresponds to
      increased MAPK activation.

PMID- 12061774
TI  - Stabilization of androgen receptor protein is induced by agonist, not by
      antagonists.
AB  - The action of nuclear receptor ligands in target tissues is specified mainly by
      the expression levels of their cognate nuclear receptors. The expression levels
      of these receptors are controlled through transcriptional and post
      transcriptional events. Among post-transcriptional events, the effect of ligand
      on nuclear receptor protein turnover still remains largely unknown. Therefore, we
      studied the effects of agonist and antagonists on the turnover of the human
      androgen receptor (hAR) protein in stably transformed Chinese hamster ovary cells
      expressing exogenous hAR. Western blot analysis showed that the most potent
      androgen, dihydrotestosterone (DHT), stabilizes hAR with the induction of the
      transactivation function of hAR. However, this androgen-induced stabilization of
      hAR protein was abrogated by well-known androgen antagonists, hydroxyflutamide
      and bicalutamide (BIC), with inhibition of the transactivation function of hAR.
      Thus, the present study suggests that androgen antagonists exert their effects
      through, at least in part, abrogating the agonist-induced stabilization of hAR
      protein as well as blocking the ligand-induced transactivation function of hAR.

PMID- 12061775
TI  - Inhibition of stearoyl-CoA desaturase activity by the cis-9,trans-11 isomer and
      the trans-10,cis-12 isomer of conjugated linoleic acid in MDA-MB-231 and MCF-7
      human breast cancer cells.
AB  - Conjugated linoleic acid (CLA) is a collective term for a group of positional and
      geometric conjugated dienoic isomers of linoleic acid. CLA has been shown to have
      strong inhibitory effects on mammary carcinogenesis both in vitro and in vivo. In
      this study, we investigated the regulation of human stearoyl-CoA desaturase (SCD,
      EC 1.14.99.5) expression by CLA in human breast cancer cell lines, MDA-MB-231 and
      MCF-7. Treatment of the cells with the cis-9,trans-11 and trans-10,cis-12 CLA
      isomers (45 microM) did not repress SCD mRNA in both MDA-MB-231 and MCF-7 cells.
      However, the cis-9,trans-11 and trans-10,cis-12 CLA isomers significantly
      decreased SCD protein levels and SCD activity in MDA-MB-231 cells. In MCF-7
      cells, both isomers did not affect protein levels, but they inhibited SCD
      activity. These results suggest that in MDA-MB-231 cells the cis-9,trans-11 and
      trans-10,cis-12 CLA isomers regulate human SCD by reducing SCD protein levels,
      while in MCF-7 cells both isomers have a direct inhibitory effect on SCD enzyme
      activity.

PMID- 12061776
TI  - TEF-1 and MEF2 transcription factors interact to regulate muscle-specific
      promoters.
AB  - Many muscle-specific genes are regulated by transcriptional enhancer factor-1
      (TEF-1), serum response factor (SRF), and myocyte enhancer factor-2 (MEF2)
      transcription factors. TEF-1 interacts with the MADS domain of SRF and together
      SRF and TEF-1 co-activate the skeletal alpha-actin promoter. MEF2 factors also
      contain a MADS domain with 50% amino acid identity to the SRF MADS domain.
      Because of this sequence divergence, some SRF co-factors do not interact with
      MEF2. To demonstrate that TEF-1 factors could also interact with MEF2 through its
      MADS domain, we used co-immunoprecipitation and GST pull-down assays in vitro and
      a mammalian two-hybrid assay in vivo. The MADS domain was not sufficient for MEF2
      interaction with TEF-1, because additional sequences in the activation domains of
      both proteins were required for in vivo association. The physiological
      significance of this interaction was also demonstrated by transient transfection
      assays using muscle-specific promoters. Our results suggest that by their
      interaction with MEF2 factors, TEF-1 factors can control MEF2-dependent muscle
      specific gene expression.

PMID- 12061777
TI  - Acute and chronic treatment of ob/ob and db/db mice with AICAR decreases blood
      glucose concentrations.
AB  - The enzyme 5'AMP-activated protein kinase (AMPK) is activated by increases in
      intracellular AMP concentration through a complex interaction of phosphorylation
      and allosteric regulation. Actions of AMPK elucidated thus far suggest that AMPK
      may be a viable target for pharmacologic intervention in type II diabetes.
      Activation of AMPK is believed to mediate both the acute increase in skeletal
      muscle glucose uptake during exercise, as well as the adaptive responses to
      chronic exercise such as regulation of expression of components of the muscle
      glucose uptake system. In addition, AMPK is known to inhibit key enzymes involved
      in lipid and cholesterol synthesis, suggesting that activation of this kinase may
      also ameliorate dyslipidemia. To investigate the effects of AMPK activation in
      animal models of type II diabetes, db/db and ob/ob mice were administered 5
      aminoimidazole-4-carboxamide 1-beta-ribofuranoside (AICAR) subcutaneously either
      acutely (single injection) or twice per day for 8 days (chronic treatment). Blood
      glucose was lowered transiently in both db/db and ob/ob mice by acute AICAR
      treatment, returning to basal levels approximately 3 h after AICAR
      administration. In response to chronic treatment, blood glucose (measured 18 h
      post-AICAR administration) was significantly decreased in both mouse models when
      compared to vehicle control groups, with morning blood glucose values on Day 8
      being decreased approximately 30-35% in both mouse models. Chronic AICAR
      administration also resulted in an elevation of total Glut4 concentration in
      skeletal muscle from ob/ob mice, but not db/db mice. In contrast to the
      beneficial effects on glucose metabolism, AICAR treatment of db/db and ob/ob mice
      led to approximately a 2.5-3-fold increase in serum triglyceride levels compared
      to vehicle-treated controls. These data suggest that pharmacological activation
      of AMPK may enhance glucose uptake in individuals with type II diabetes, however,
      this benefit may be offset by the concomitant elevation in triglycerides.

PMID- 12061778
TI  - Allosteric mechanisms in P450eryF probed with 1-pyrenebutanol, a novel
      fluorescent substrate.
AB  - 1-Pyrenebutanol (1-PB) has been used as a new fluorescent substrate for P450eryF
      to explore the molecular mechanisms of cooperativity. Hydroxylation of 1-PB by
      P450eryF was detected by both fluorometric and chromatographic assays. Binding
      was monitored by a substrate-induced low-to-high spin shift, as well as by
      fluorescence resonance energy transfer (FRET) from 1-PB to the heme.
      Spectrophotometric titration showed that P450eryF has high affinity for 1-PB with
      distinct positive cooperativity (S(50) = 12.4 +/- 2.2 microM, n = 2.3 +/- 0.6),
      as also revealed in activity measurements. FRET analysis showed a different
      binding process obeying a simple bimolecular mechanism with a K(D) = 2.15 +/- 0.8
      microM that suggests the presence of the higher affinity binding site. 1-PB
      binding at this site appears not to modulate the spin state directly but rather
      to facilitate the spin shift caused by the interactions of P450eryF with the
      other substrate molecule.

PMID- 12061779
TI  - Generation and characterization of novel monoclonal antibodies to the Ret
      receptor tyrosine kinase.
AB  - Ret is a tyrosine kinase receptor involved in several human diseases germ-line
      mutations are responsible for multiple endocrine neoplasia type 2 syndromes while
      somatic mutations of Ret are found in sporadic medullary thyroid carcinomas. In
      the present work, we describe the generation and characterization of a panel of
      novel monoclonal antibodies to Ret obtained by immunizing mice with a Ret-FC
      fusion protein. Fifty-five independent monoclonal antibodies recognize Ret-FC by
      enzyme linked immunosorbent assay but not a non-related FC fusion protein. Twenty
      antibodies further characterized recognize Ret expressing cells by flow
      cytometry. Finally, immunoprecipitation analysis showed that these antibodies
      recognize Ret mature glycosylated and immature forms. Thus, these monoclonal
      antibodies could be used as diagnostic tools to detect Ret expression, as well as
      therapeutic tools to downmodulate Ret or to deliver cytotoxic drugs to
      malignancies that overexpress Ret as neuroblastomas, medullary and papillary
      thyroid carcinomas, seminomas, and leukemia.

PMID- 12061780
TI  - GTP is required to stabilize and display transamidation activity of
      transglutaminase 2.
AB  - Transglutaminase 2 (TGase 2) is a bifunctional enzyme that catalyzes calcium
      dependent transamidation and GTP binding/hydrolysis. The transamidation activity
      is proposed to be associated with several neurodegenerative disorders such as
      Alzheimer's and Hungtinton's disease. However, the regulation mechanism by which
      TGase 2 causes neurodegeneration is unknown. In this study, we show that two
      activities of TGase 2 have a differential stability; transamidation activity is
      less stable than GTP hydrolytic activity, and that GTP was required to stabilize
      and to display transamidation activity. Moreover, GTP binding-defective mutant of
      TGase 2 did not show any transamidation activity in transfection experiments.
      These results indicate that GTP binding is crucial for transamidation activity of
      TGase 2, suggesting that protein cross-linking by TGase 2 might be associated
      with G-protein coupled receptor signaling system. Thus, our data could contribute
      to understand the regulation of TGase 2 activity and TGase 2-associated
      pathogenesis.

PMID- 12061781
TI  - Palmitoylcarnitine modulates interaction protein kinase C delta-GAP-43.
AB  - Palmitoylcarnitine, reported previously to promote neuronal differentiation, was
      observed to affect distribution of protein kinase C (PKC) isoforms in
      neuroblastoma NB-2a cells, leading to retardation in cytoplasm of high molecular
      weight species of PKCbeta and delta. Growth cone protein-GAP-43, a PKC substrate,
      was co-immunoprecipitated with all the conventional and novel PKCs:
      palmitoylcarnitine, however, decreased its amount exclusively in the complex with
      PKCdelta. Administration of palmitoylcarnitine, although did not change the
      subcellular distribution of GAP-43, decreased its phosphorylation, which could
      regulate other signal transduction pathways (calmodulin and G(0)-dependent).

PMID- 12061782
TI  - O(2)-dependent stimulation of the pentose phosphate pathway by S-nitrosocysteine
      in human erythrocytes.
AB  - In the present study we analysed the effects of S-nitrosocysteine (CysNO) on
      adult human red blood cell metabolism and observed that metabolic response
      depended on the degree of cell oxygenation. In particular, glucose metabolised
      through the pentose phosphate pathway (PPP) was higher in treated erythrocytes
      than in untreated cells only at high O(2) pressure. Since, following the
      treatment of intact cells with CysNO, glucose-6-phosphate dehydrogenase (G6PD)
      and phosphofructokinase (PFK) activities did not evidence any significant
      alteration, the possibility that the stimulation of PPP was triggered by a CysNO
      mediated modification of these enzymes was excluded. Intracellular S
      nitrosoglutathione (GSNO), detected only in treated red blood cells, may be
      linked solely to the exposition to the NO donor. A possible rationalisation of
      the different metabolic behaviour shown by erythrocytes as a function of their
      oxygenation state is proposed. It takes into account the different route of
      catabolic degradation observed in vitro for GSNO under aerobic and anaerobic
      condition.

PMID- 12061783
TI  - Human secretory signal peptide description by hidden Markov model and generation
      of a strong artificial signal peptide for secreted protein expression.
AB  - A hidden Markov model (HMM) has been used to describe, predict, identify, and
      generate secretory signal peptide sequences. The relative strengths of artificial
      secretory signals emitted from the human signal peptide HMM (SP-HMM) correlate
      with their HMM bit scores as determined by their effectiveness to direct alkaline
      phosphatase secretion. The nature of the signal strength is in effect the
      closeness to the consensus. The HMM bit score of 8 is experimentally determined
      to be the threshold for discriminating signal sequences from non-secretory ones.
      An artificial SP-HMM generated signal sequence of the maximum model bit score
      (HMM + 38) was selected as an ideal human signal sequence. This signal peptide
      (secrecon) directs strong protein secretion and expression. We further ranked the
      signal strengths of the signal peptides of the known human secretory proteins by
      SP-HMM bit scores. The applications of high-bit scoring HMM signals in
      recombinant protein production and protein engineering are discussed.

PMID- 12061784
TI  - A novel beta1,3-N-acetylglucosaminyltransferase involved in invasion of cancer
      cells as assayed in vitro.
AB  - Using a two-step screening system for genes involved in tissue invasion [Kataoka
      et al., Cancer Lett. 163(2) (2001) 213], we identified a cDNA whose expression
      level was higher in mouse placenta at later stages of gestation and in sublines
      of cancer cells with low degrees of invasiveness. The deduced amino acid sequence
      showed relatively high similarity with beta1,3-N-acetylglucosaminyltransferase2
      approximately 5 (beta3GnT2 approximately 5), and the protein was therefore named
      beta3GnT7. A possible human ortholog was identified and its chromosomal locus was
      determined to be 2q37.1. In the mouse, beta3GnT7 was most strongly expressed in
      the placenta and colon. Moderate amounts of mRNA were detected in the lung,
      stomach, small intestine, and kidney. The expression of beta3GnT7 was very weak
      in the cerebrum, cerebellum, heart, and testis. Transfection of the antisense
      oligonucleotide significantly enhanced the motility of a lung cancer cell line
      (KLN205-MUC1) in a monolayer compared to the controls. Furthermore, the antisense
      oligonucleotide increased the number of cells that invaded the matrix-coated
      membrane in an in vitro invasion model. These results indicate that beta3GnT7 may
      play a role in preventing cells from migrating out of the original tissues and
      invading surrounding tissues.

PMID- 12061785
TI  - Dilinoleoylphosphatidylcholine decreases LPS-induced TNF-alpha generation in
      Kupffer cells of ethanol-fed rats: respective roles of MAPKs and NF-kappaB.
AB  - Activation of Kupffer cells by lipopolysaccharide (LPS) after ethanol feeding
      results in overproduction of TNF-alpha, leading to liver injury. Since
      dilinoleoylphosphatidylcholine (DLPC) protects against liver injury and has
      antioxidant properties, we investigated whether it alters LPS signaling leading
      to decreased TNF-alpha production. Kupffer cells were isolated from rats fed
      alcohol-containing or isocaloric control diets for 3 weeks. With ethanol,
      cytochrome P4502E1 was upregulated. When stimulated with LPS in culture, Kupffer
      cells released more TNF-alpha compared to control rats; DLPC diminished the
      increase. It also reduced ERK1/2 and p38 phosphorylation as well as NF-kappaB
      activation with decreased nuclear p65 and increased cytosolic IkappaB-alpha
      expression. ERK1/2 and NF-kappaB activation were abolished by the ERK1/2
      inhibitor PD098059. The p38 inhibitor SB203580 abolished p38 activation without
      affecting NF-kappaB. Both inhibitors reduced TNF-alpha generation. Thus, DLPC
      diminishes LPS-dependent TNF-alpha generation by inhibiting p38 and ERK1/2
      activation; the latter leads to decreased NF-kappaB activation.

PMID- 12061786
TI  - Dual regulatory role of human cytomegalovirus immediate-early protein in IL1B
      transcription is dependent upon Spi-1/PU.1.
AB  - Activation of IL1B gene transcription has been shown to play a crucial role in
      human cytomegalovirus (HCMV) infection. We previously reported that HCMV
      immediate-early (IE) proteins vigorously transactivate IL1B expression without
      the need for a normally essential upstream enhancer. This activation appears to
      depend upon protein-protein tethering between IE2, which provides a transcription
      activation domain (TAD), and the DNA-binding domain of the transcription factor
      Spi-1. We now show a distinct mechanism by which IE1 and IE2 mediate both weak
      Spi-1-independent and vigorous Spi-1-dependent IL1B transcription from the -59 to
      +12 IL1B core promoter. These results demonstrate that in contrast to non-viral,
      enhancer-mediated, transactivation of IL1B, the IE mechanism is not absolutely
      dependent upon Spi-1. However, Spi-1 is required for vigorous transcription.
      Additionally, we have discovered that IE1, which cooperates with IE2 to
      transactivate IL1B, has minimal activity in the absence of IE2 and Spi-1.
      Furthermore, IE1 is a dual-acting factor, which can either activate or repress
      IL1B, depending on the presence of both IE2 and the Spi-1 TADs. Therefore, the
      relative expression of IE1 and IE2, which varies during HCMV infection, may
      provide a molecular mechanism by which IL1B can be repressed, thus, avoiding
      clearance by the host.

PMID- 12061787
TI  - Establishment and characterization of immortal hepatocytes derived from various
      transgenic mouse lines.
AB  - The potential of three genetic changes introduced into mice by the transgenic or
      knockout technology aimed at immortalizing hepatocytes in vitro and concomitantly
      preserving their differentiated hepatic functions was analyzed. Six hepatocyte
      lines were isolated from neonatal and adult transgenic mice expressing either
      IgEGF (a secretable variant of hEGF) or SV40 T antigen in the liver and from
      neonatal and adult p53 knockout (KO) mice and have been subcultured >150 times in
      serum-free, arginine-deficient medium. Only in SV40 T antigen transgenic lines
      profiles of mRNAs encoding serum proteins, transcription factors, and liver
      specific enzymes were similar to those found in livers and primary hepatocytes.
      Accordingly, these cells displayed basal and inducible expression of CYP proteins
      as well as testosterone metabolizing activities. Thus, either knockout of the p53
      gene or expression of SV40 T antigen or of IgEGF imparts immortality to
      hepatocytes in vitro, but only SV40 T antigen expression is compatible with the
      concomitant long-term preservation of differentiated liver functions.

PMID- 12061788
TI  - DNA fragmentation and morphological changes in apoptotic human lymphocytes.
AB  - Cell suspensions enriched in cells at various stages of apoptosis were obtained
      by separation of irradiated human peripheral blood lymphocytes on density
      gradients at different post-irradiation times. The state of DNA fragmentation in
      the cells was determined by comet assay and pulsed field gel electrophoresis. The
      morphologically distinguishable features of apoptosis such as chromatin
      condensation and cell shrinkage correlated with discrete stages of DNA
      fragmentation. It was found that >/=50 kbp fragmentation of DNA occurs already in
      cells of normal density whereas the subsequent DNA fragmentation onto fragments
      <50 kbp occurs in parallel with cell shrinkage and simultaneous increase in cell
      density. The observed stages of DNA fragmentation seem to be separated in time
      that could allow in case of abortive apoptosis formation of chromosomal
      aberrations.

PMID- 12061789
TI  - Angiostatin-like molecules are generated by snake venom metalloproteinases.
AB  - Angiostatin is a plasminogen-derived anti-angiogenic factor composed of its first
      four kringle structures. This molecule is generated by proteolytic cleavage of
      plasminogen by some proteolytic enzymes in vitro. Since venoms of viper snakes
      are a rich source of both serine- and metalloproteinase, we hypothesized that
      angiostatin-like polypeptides could be generated during the envenomation after
      snake bites and play a pathophysiological role in the local tissue damage and
      regeneration. Our results showed that crude venoms from several species of
      Bothrops snakes were able to generate angiostatin-like polypeptides and purified
      metalloproteinases but not serine proteinases from Bothrops jararaca and Bothrops
      moojeni venoms were responsible for their generation in vitro. The putative
      plasminogen cleavage sites by the crude venoms and purified proteinases were
      determined by N-terminal amino acid sequencing of the angiostatin-like molecules.
      Angiostatin-like peptides derived from human plasminogen digestion by jararhagin,
      a metalloproteinase isolated from B. jararaca venom, inhibited endothelial cell
      proliferation in vitro. These results indicate that angiostatin-like molecules
      can be generated upon snakebite envenomations and may account for the poor and
      incomplete regenerative response observed in the damaged tissue.

PMID- 12061791
TI  - GroEL interacts transiently with oxidatively inactivated rhodanese facilitating
      its reactivation.
AB  - When the enzyme rhodanese was inactivated with hydrogen peroxide (H(2)O(2)), it
      underwent significant conformational changes, leading to an increased exposure of
      hydrophobic surfaces. Thus, this protein seemed to be an ideal substrate for
      GroEL, since GroEL uses hydrophobic interactions to bind to its substrate
      polypeptides. Here, we report on the facilitated reactivation (86%) of H(2)O(2)
      inactivated rhodanese by GroEL alone. Reactivation by GroEL required a reductant
      and the enzyme substrate, but not GroES or ATP. Further, we found that GroEL
      interacted weakly and/or transiently with H(2)O(2)-inactivated rhodanese. A
      strong interaction with rhodanese was obtained when the enzyme was pre-incubated
      with urea, indicating that exposure of hydrophobic surfaces alone on oxidized
      rhodanese was not sufficient for the formation of a strong complex and that a
      more unfolded structure of rhodanese was required to interact strongly with
      GroEL. Unlike prior studies that involved denaturation of rhodanese through
      chemical or thermal means, we have clearly shown that GroEL can function as a
      molecular chaperone in the reactivation of an oxidatively inactivated protein.
      Additionally, the mechanism for the GroEL-facilitated reactivation of rhodanese
      shown here appears to be different than that for the chaperonin-assisted folding
      of chemically unfolded polypeptides in which a nucleotide and sometimes GroES is
      required.

PMID- 12061790
TI  - Effects of metallic silver particles on resonance energy transfer in labeled
      bovine serum albumin.
AB  - Resonance energy transfer (RET) is widely used to detect proximity between
      biomolecules. In transparent solution the maximum donor-to-acceptor distance for
      RET is about 70 A. We measured the effects of metallic silver island films on RET
      from the intrinsic tryptophan of a protein to a bound probe as the acceptor.
      These preliminary experiments revealed a dramatic increase in the apparent
      Forster distance increasing from 28.6 to 63 A. These results suggest the use of
      silver island films for detecting long range proximity between biomolecules and
      for biotechnology applications based on RET.

PMID- 12061792
TI  - CAS/CSE 1 stimulates E-cadhrin-dependent cell polarity in HT-29 human colon
      epithelial cells.
AB  - The establishment and maintenance of epithelial polarity are crucial for tissue
      organization and function in mammals. Epithelial cadherin (E-cadherin) is
      expressed in epithelial cell membrane and is important for cell-cell adhesion,
      intercellular junctions formation, as well as epithelial cell polarization. We
      report herein that CAS (CAS/CSE 1), the human cellular apoptosis susceptibility
      protein, interacts with E-cadherin and stimulates polarization of HT-29 human
      colon epithelial cells. CAS binds with E-cadherin but not with beta-catenin in
      the immunoprecipitation assays. Interaction of CAS with E-cadherin enhances the
      formation of E-cadherin/beta-catenin cell-cell adhesive complex. Electron
      microscopic study demonstrated that CAS overexpression in cells stimulates
      intercellular junction complex formation. The disorganization of cellular
      cytoskeleton by cytochalasin D, colchicine, or acrylamide treatment disrupts CAS
      stimulated HT-29 cell polarization. CAS-mediated HT-29 cell polarity is also
      inhibited by antisense E-cadherin DNA expression. Our results indicate that CAS
      cooperates with E-cadherin and plays a role in the establishment of epithelial
      cell polarity.

PMID- 12061793
TI  - A new organotypic culture of thyroid tissue maintains three-dimensional follicles
      with C cells for a long term.
AB  - Thyroid follicles embedded in extracellular matrix (ECM) seem to be supplied
      enough oxygen by a dense network of capillaries in vivo. Air exposure (AE) causes
      cells to increase oxygen availability in vitro. We speculated that three
      dimensional (3D) environment of ECM together with AE may be applied to a thyroid
      tissue-organotypic culture, simply simulating such a microenvironment of
      follicles. To address the issue, we performed 3D collagen gel culture of minced
      thyroid tissues with or without AE. Most follicles in the tissues without AE died
      within 7 days. In culture with AE, most of the follicles with calcitonin-positive
      C cells were kept for over one month. Immunohistochemistry showed that thyrocytes
      displayed thyroglobulin, thyrotropin receptor, thyroid transcription factor-1
      (TTF-1), and pendrin, which are all crucial for thyroid function. C cells
      expressed calcitonin gene-related peptide and TTF-1. Our study is the first
      demonstration that 3D collagen gel culture with AE retains 3D thyroid follicles
      with C cells for a long term. This suggests that ECM and oxygen supply together
      may be crucial for maintenance of 3D follicle structure and function. Our method
      will possibly open a new path to the study of thyrocyte-C cell interaction and
      thyroid biology.

PMID- 12061794
TI  - cDNA sequence and tissue expression of Fugu rubripes prion protein-like: a
      candidate for the teleost orthologue of tetrapod PrPs.
AB  - We report the isolation and characterization of a cDNA coding for Fugu rubripes
      prion protein (PrP)-like of 180 amino acids which includes the PrP-conserved
      hydrophobic region homologous to that of Xenopus PrP. In addition to the
      hydrophobic region, Fugu PrP-like has several features common to PrPs, such as a
      signal sequence, a basic nature (pI 9.7) and a single intron in the 5'
      untranslated region. A possible glycosyl phosphatidylinositol (GPI) anchor site
      also exists in PrP-like. In expression analysis, PrP-like mRNA was detected in
      retina, skin, and brain, all of which express PrP mRNA in mammals. In a genome
      fragment clone (T002589, 31945 bp) sequenced by the Fugu Genomics Project, PrP
      like located between KIAA0168 and SLC231A homologues. In human chromosome 20p13,
      PrP, Doppel, KIAA0168, and SLC231A align in this order. The close gene
      arrangement between the Fugu and human genomes suggests that Fugu PrP-like is a
      real orthologue of human PrP. However, Fugu PrP-like does not possess tandem
      repeats or a region with two glycosylation sites and a disulphide bridge. We do
      not declare that the cloned Fugu PrP-like represents fish PrP due to structural
      inconsistency, but believe that it will offer new insights into the evolution of
      PrPs from fish to tetrapods.

PMID- 12061795
TI  - The hyaluronan receptor for endocytosis (HARE) is not CD44 or CD54 (ICAM-1).
AB  - Mammalian liver contains an endocytic, recycling receptor that mediates the
      clearance of hyaluronan (HA) and chondroitin sulfate from the circulation.
      McCourt et al. [J. Biol. Chem. 269 (1994) 30081] previously reported that this
      endocytic liver HA receptor was ICAM-1. In contrast, we purified this HA receptor
      for endocytosis (HARE) from rat liver sinusoidal endothelial cells (LECs) and
      obtained two novel large proteins [Zhou et al., J. Biol. Chem. 274 (1999) 33831].
      The goal of the present study was to clarify this inconsistency and determine
      whether CD44, which is also an HA receptor, or ICAM-1 (CD54) is identical to, or
      is part of, HARE. Although isolated liver LECs contain HARE, CD44, and ICAM-1,
      confocal fluorescence microscopy showed that the two latter proteins have
      cellular distributions that are distinct from and essentially nonoverlapping with
      HARE. HA accumulation by cultured LECs was inhibited >98% by an antibody against
      HARE and unaffected by antibodies to ICAM-1 or CD44, indicating that virtually
      all specific HA uptake is mediated by HARE and not by ICAM-1 or CD44. Finally, no
      reactivity was observed against purified HARE in an ELISA-based assay using CD44
      or ICAM-1 antibodies. The results confirm that the mammalian endocytic HA
      receptor is HARE and is not ICAM-1 or CD44.

PMID- 12061796
TI  - Thermodynamics of drug-DNA interactions.
AB  - Many anticancer, antibiotic, and antiviral drugs exert their primary biological
      effects by reversibly interacting with nucleic acids. Therefore, these
      biomolecules represent a major target in drug development strategies designed to
      produce next generation therapeutics for diseases such as cancer. In order to
      improve the clinical efficacy of existing drugs and also to design new ones it is
      necessary to understand the molecular basis of drug-DNA interactions in
      structural, thermodynamic, and kinetic detail. The past decade has witnessed an
      increase in the number of rigorous biophysical studies of drug-DNA systems and
      considerable knowledge has been gained in the energetics of these binding
      reactions. This is, in part, due to the increased availability of high
      sensitivity calorimetric techniques, which have allowed the thermodynamics of
      drug-DNA interactions to be probed directly and accurately. The focus of this
      article is to review thermodynamic approaches to examining drug-DNA recognition.
      Specifically, an overview of a recently developed method of analysis that
      dissects the binding free energy of these reactions into five component terms is
      presented. The results of applying this analysis to the DNA binding interactions
      of both minor groove drugs and intercalators are discussed. The solvent water
      plays a key role in nucleic acid structure and consequently in the binding of
      ligands to these biomolecules. Any rational approach to DNA-targeted drug design
      requires an understanding of how water participates in recognition and binding
      events. Recent studies examining hydration changes that accompany DNA binding by
      intercalators will be reviewed. Finally some aspects of cooperativity in drug-DNA
      interactions are described and the importance of considering cooperative effects
      when examining these reactions is highlighted.

PMID- 12061797
TI  - Rapid release of Mg(2+) from liver mitochondria by nonesterified long-chain fatty
      acids in alkaline media.
AB  - Long-chain fatty acids induce a rapid release of Mg(2+) from both energized and
      nonenergized rat liver mitochondria suspended at pH 8 in isotonic saline but not
      sucrose media. The effect is observed only with fatty acids that possess
      protonophoric activity. The most active saturated fatty acids are myristic and
      palmitic, while the most active unsaturated acids are oleic, linolenic, and
      arachidonic. The rate of Mg(2+) release drastically decreases with decreasing
      medium pH to 7.2-7.6. However, at those pH values this rate is doubled by
      energization of mitochondria with respiratory substrates. Mg(2+) release is
      accompanied by cyclosporin A-insensitive large-amplitude swelling of
      mitochondria. This swelling is similar to that produced by the divalent metal
      ionophore A23187 and is interpreted as being due to activation of the inner
      membrane anion channel, the K(+) uniporter, and the K(+)/H(+) exchanger. In
      energized mitochondria, both swelling and Mg(2+) release are blocked by the
      exogenous K(+)/H(+) exchanger nigericin. It is proposed that fatty acids under
      conditions of alkaline mitochondrial matrix activate latent Mg(2+)-sensitive ion
      conducting pathways in the inner mitochondrial membrane, which mediate swelling
      and Mg(2+) release. It is hypothesized that fatty acids activate an intrinsic
      Mg(2+)/H(+) exchanger that is related to, or identical with, the K(+)/H(+)
      exchanger.

PMID- 12061799
TI  - Decrease in acetylcholine-induced current by neomycin in PC12 cells.
AB  - The effects of neomycin, one of the aminoglycoside antibiotics, on the
      acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma
      cells by using the whole-cell clamp technique. The I(ACh) proved to be generated
      through neuronal nicotinic receptor. ACh (30 microM) induced an inward current at
      a holding potential of -80 mV. When cells were treated with neomycin (0.01-1 mM)
      and ACh (30 microM) simultaneously, an inhibitory effect of neomycin on the peak
      of I(ACh) was found. This effect was fast, reversible, and concentration
      dependent. Pretreatment with neomycin for 3-8 min had no effect on the inhibition
      of I(ACh) induced by neomycin. External application of 0.1 mM neomycin neither
      shifted the dose-response curve of the peak I(ACh) to the right (dissociation
      constant (K(d)) = 16.5 microM) nor affected its coefficient (1.8) but inhibited
      the curve amplitudes by approximately 33%. Stimulated protein kinase C activation
      by using an exogenous activator produced inhibition of I(ACh), while using
      protein kinase C inhibitor (PKCI 19-31) had no effect on the inhibition of I(ACh)
      induced by neomycin. These results suggest that neomycin has an inhibitory effect
      on I(ACh) without the involvement of phospholipase C. It indicates that neomycin
      binds to a specific site on the cell membrane, probably on the neuronal nicotinic
      receptor-coupled channel, and inhibits the I(ACh) in a noncompetitive manner,
      thus controlling the immediate catecholamine release from the sympathetic cells.

PMID- 12061798
TI  - Characterization of substrate specificity of plant FatA and FatB acyl-ACP
      thioesterases.
AB  - The specificity of plant acyl-acyl carrier protein (ACP) thioesterases is the
      major determinant of the chain length and level of saturated fatty acids found in
      most plant tissues. Although these enzymes have been previously characterized
      from a number of sources, information on kinetic parameters for a wide range of
      substrates with cloned enzymes is lacking. In the present study the substrate
      specificity of recombinant FatA thioesterase isoforms from Arabidopsis (AtFatA)
      and coriander (CsFatA) and FatB from Arabidopsis (AtFatB) have been re-examined
      with a comprehensive range of substrates including 14:1-ACP and 16:1-ACP. AtFatA
      displayed the highest catalytic efficiencies (kcat/Km) towards oleoyl-ACP with
      activities at least 20-fold lower for all other tested substrates and 75-fold
      lower with palmitoyl-ACP. Both chain length and double bond presence strongly
      influenced kcat of FatA with minor influence on Km. Arabidopsis FatB substrate
      specificity was found to differ from previous reports and this difference could
      be attributed to the influence of ACP structure. FatB activity with palmitoyl-ACP
      was 2.5-fold higher and the ratio of 16:0-ACP/14:0-ACP hydrolysis was 6.4-fold
      higher with spinach ACP compared to E. coli ACP. Additionally, the influence of
      amino acid domains from both AtFatA and AtFatB on their substrate specificity was
      studied by utilizing a domain-swapping approach. The characterization of the
      resulting chimeric enzymes pointed to the N-terminus as a determinant of the
      substrate specificity for both FatA and FatB acyl-ACP thioesterases.

PMID- 12061800
TI  - New selective inhibitors of cytochromes P450 2B and their application to
      antimutagenesis of tamoxifen.
AB  - 2-Isopropenyl-2-methyladamantane (2-PMADA) and 3-isopropenyl-3-methyldiamantane
      (3-PMDIA) showed potent and selective inhibition of cytochrome P450 (CYP) 2B6
      mediated reactions with K(i) values of 5.27 and 2.17 microM, respectively. No
      effect on activities of other human CYP was found even at concentrations 100-fold
      higher than those inhibiting CYP2B6. These results indicate that 2-PMADA and 3
      PMDIA belong among the most potent CYP2B6-selective inhibitors discovered to
      date. Both compounds also inhibited reactions catalyzed by CYP2B2 and CYP2B4 with
      K(i) values ranging between 0.23 and 2 microM. They are competitive inhibitors of
      all CYP2B. The activation of the anticancer drug tamoxifen by human and rabbit
      microsomes generating tamoxifen-DNA adducts, which are responsible for
      carcinogenic side effects of this drug, was strongly inhibited by both compounds.
      2-PMADA and 3-PMDIA are very potent for inhibition of formation of these DNA
      adducts and warrant consideration as candidates for preventing endometrial cancer
      development by tamoxifen in humans treated with this anticancer drug.

PMID- 12061802
TI  - Action spectra for the photoconsumption of oxygen by human ocular lipofuscin and
      lipofuscin extracts.
AB  - The action spectra for the photoconsumption of oxygen by lipofuscin isolated from
      human retinal pigment epithelium cells and liposomal suspensions containing
      extracts of lipofuscin are reported. The lipofuscin and lipofuscin extract action
      spectra are similar, demonstrating the phototoxic constituents of lipofuscin are
      present in the lipofuscin solvent extract. 2-[2,6-Dimethyl-8-(2,6,6-trimethyl-1
      cyclohexen-1-yl)-1E,3E,5E,7E-octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6
      (2,6,6-trimethyl-1-cyclohexen-1-yl)-1E,3E,5E-hexatrienyl]-pyridinium (A2E),
      present in both intact granules and the solvent extract, has been invoked as an
      important contributor to the phototoxicity of lipofuscin. The action spectrum for
      oxygen photoconsumption by A2E follows its absorption spectrum but does not
      resemble the action spectrum for photoconsumption of oxygen by lipofuscin
      granules or lipofuscin extract. These results combined with recently reported
      experimental studies on the aerobic photoreactivity of A2E indicate that it is
      not a major contributor to the phototoxicity of lipofuscin.

PMID- 12061801
TI  - Activation of caspases and cleavage of Bid are required for tyrosine and
      phenylalanine deficiency-induced apoptosis of human A375 melanoma cells.
AB  - Deprivation of tyrosine (Tyr) and phenylalanine (Phe) inhibits growth and induces
      programmed cell death (apoptosis) of human A375 melanoma cells. Herein, we found
      that activation of caspases and release of mitochondrial cytochrome c are
      required for this process. Culturing A375 cells in Tyr/Phe-free medium,
      containing 10% dialyzed fetal bovine serum, results in activation of caspase-3
      like activity. This is accompanied by decreased cell viability and increased
      apoptosis. Tyr/Phe deprivation also stimulates proteolytic cleavage of the DNA
      repair enzyme, poly(ADP-ribose) polymerase (PARP). Western blot analysis showed
      that caspases 3, 7, 8, and 9 are activated by deprivation of Tyr/Phe. Tyr/Phe
      deprivation decreases mitochondrial membrane potential, induces cleavage of Bid,
      increases translocation of Bax from the cytosol to mitochondria, and results in
      release of cytochrome c from the mitochondria to the cytosol. Apoptosis due to
      Tyr/Phe deprivation is almost completely inhibited by the broad-spectrum cell
      permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone
      (Z.VAD.fmk). This inhibitor suppresses the cleavage of Bid, the release of
      cytochrome c from the mitochondria to the cytosol, and the cleavage of PARP.
      Decylubiquinone, a mitochondrial permeability transition pore inhibitor, does not
      suppress the activation of caspase 8 but suppresses release of cytochrome c,
      activation of caspase 9, and induction of apoptosis. These results indicate that
      activation of caspases, cleavage of Bid, and mitochondrial release of cytochrome
      c are required for apoptosis induced by Tyr/Phe deprivation.

PMID- 12061803
TI  - The molecular chaperone DnaK is not recruited to translating ribosomes that lack
      trigger factor.
AB  - The molecular chaperone DnaK and trigger factor (TF), a ribosome-associated
      protein with folding activity, have been implicated in assisting nascent
      polypeptides to acquire a three-dimensional structure on Escherichia coli
      ribosomes. We asked whether ribosomes that lack trigger factor would recruit DnaK
      for synthesis and folding of nascent peptides. For these analyses, translating
      ribosomes with a homogeneous population of nascent peptides were isolated.
      Truncated forms of rhodanese and E. coli translation initiation factor 3 (IF3)
      were generated with tandem rare arginine codons in the coding sequence. These
      codons cause strong translational pausing during coupled
      transcription/translation in E. coli extracts, generating nascent polypeptides on
      ribosomes. Protein synthesis in the TF(-) extract was initiated with biotin-Met
      tRNA(f). Ribosomes with nascent polypeptides were isolated by interaction of the
      N-terminal biotin with streptavidin on magnetobeads. These translating ribosomes
      that lack TF contain the molecular chaperone DnaK in considerably less than
      stoichiometric amounts.

PMID- 12061804
TI  - Protein kinase C-zeta phosphorylates insulin-responsive aminopeptidase in vitro
      at Ser-80 and Ser-91.
AB  - Insulin-responsive aminopeptidase (IRAP) colocalizes with glucose transporter
      type 4 (GLUT4) in adipocytes and is recruited to the plasma membrane in response
      to insulin. Microinjection of peptides corresponding to the IRAP cytoplasmic
      domain sequences causes GLUT4 recruitment in adipocytes. Inhibitors of protein
      kinase C-zeta (PKC-zeta) abolish the insulin-induced GLUT4 recruitment in rat
      adipocytes. These findings suggest an interesting possibility that PKC-zeta may
      phosphorylate IRAP, playing a key role in GLUT4/IRAP recruitment. To test this
      possibility, here we studied the (32)P incorporation into IRAP catalyzed by PKC
      zeta in insulin-stimulated cells. There was a small but significant (32)P
      incorporation into IRAP in rat adipocytes, which was partly abolished upon
      addition of a PKC-zeta pseudosubstrate, suggesting that PKC-zeta may be
      responsible in part for the IRAP phosphorylation in adipocytes. PKC-zeta also
      catalyzed the incorporation of (32)P not only into IRAP in GLUT4 vesicles
      isolated from rat adipocytes but also into the IRAP cytoplasmic domain inserts in
      glutathione S-transferase-fusion proteins, demonstrating direct IRAP
      phosphorylation by PKC-zeta. Reversed-phase HPLC, matrix-assisted laser
      desorption ionization mass spectrometry, and radiosequencing of the tryptic
      digests of the (32)P-labeled IRAP fusion proteins identified Ser-80 and Ser-91 as
      major phosphorylation sites. In GLUT4 vesicles, the (32)P incorporation into IRAP
      was exclusively localized at a 6.9-kDa tryptic fragment identified as IRAP(76
      138) and the (32)P labeling at Ser-80 accounted for 80-90% of the total IRAP
      labeling, suggesting that Ser-80 is the major phosphorylation site in intact
      IRAP. These findings are consistent with the possibility that the IRAP
      cytoplasmic domain phosphorylation by PKC-zeta plays a key role in insulin
      induced IRAP or GLUT4 recruitment in adipocytes.

PMID- 12061805
TI  - Effect of light and protein phosphorylation on photoreceptor rod outer segment
      acyltransferase activity.
AB  - Rod outer segments (ROS) exhibit high acyltransferase (AT) activity, the
      preferred substrate of which being lysophosphatidylcholine. To study factors
      possibly regulating ROS AT activity purified ROS membranes were assayed under
      conditions under which protein kinase C (PKC), cAMP-dependent protein kinase
      (PKA), and phosphatases were stimulated or inhibited. PKC activation produced a
      significant increase in the acylation of phosphatidylethanolamine (PE) and
      phosphatidylinositol (PI) with oleate, it inhibited phosphatidylcholine (PC)
      acylation, and phosphatidylserine (PS) and phosphatidic acid (PA) acylation
      remained unchanged. ROS PKA activation resulted in increased oleate incorporation
      into PS and PI while the acylation of PC, PE, and PA remained unchanged.
      Inhibition of ROS PKC or PKA produced, as a general trait, inverse effects with
      respect to those observed under kinase-stimulatory conditions. ROS phosphatase 2A
      was inhibited by using okadaic acid, and the changes observed in AT activity are
      described. These findings suggest that changes in ROS protein phosphorylation
      produce specific changes in AT activity depending on the phospholipid substrate.
      The effect of light on AT activity in ROS membranes was also studied and it is
      reported that acylation in these membranes remains unchanged independent of the
      illumination condition used.

PMID- 12061806
TI  - Complex effects of sulfhydryl reagents on ligand interactions with nucleoside
      transporters: evidence for multiple populations of ENT1 transporters with
      differential sensitivities to N-ethylmaleimide.
AB  - Functional studies have implicated cysteines in the interaction of ligands with
      the ENT1 nucleoside transporter. To better define these interactions, N
      ethylmaleimide (NEM) and p-chloromercuribenzylsulfonate (pCMBS) were tested for
      their effects on ligand interactions with the [(3)H] nitrobenzylthioinosine
      (NBMPR) binding site of the ENT1 transporters of mouse Ehrlich ascites cells and
      human erythrocytes. NEM had biphasic, concentration-dependent effects on NBMPR
      binding to intact Ehrlich cells, plasma membranes, and detergent-solubilized
      membranes, with about 35% of the binding activity being relatively insensitive to
      NEM inhibition. NBMPR binding to human erythrocyte membranes also displayed
      heterogeneity in that about 33% of the NBMPR binding sites remained, albeit with
      lower affinity for NBMPR, even after treatment with NEM at concentrations in
      excess of 1 mM. However, unlike that seen for Ehrlich cells, no "reversal" in
      NBMPR binding to human erythrocyte membranes was observed at the higher
      concentrations of NEM. pCMBS inhibited 100% of the NBMPR binding to both Ehrlich
      cell and human erythrocyte membranes, but had no effect on the binding of NBMPR
      to intact cells. The effects of NEM on NBMPR binding could be prevented by
      coincubation of membranes with nonradiolabeled NBMPR, adenosine, or uridine.
      Treatment with NEM and pCMBS also decreased the affinity of other nucleoside
      transport inhibitors for the NBMPR binding site, but enhanced the affinities of
      nucleoside substrates. These data support the existence of at least two
      populations of ENT1 in both erythrocyte and Ehrlich cell membranes with
      differential sensitivities to NEM. The interaction of NEM with the mouse ENT1
      protein may also involve additional sulphydryl groups not present in the human
      ENT1.

PMID- 12061807
TI  - Mitochondrial recycling of ascorbic acid from dehydroascorbic acid: dependence on
      the electron transport chain.
AB  - Mitochondria can regenerate ascorbic acid from its oxidized forms, which may help
      to maintain the vitamin both in mitochondria and in the cytoplasm. In this work,
      we sought to determine the site and mechanism of mitochondrial ascorbate
      recycling from dehydroascorbic acid. Rat skeletal muscle mitochondria incubated
      for 3 h at 37 degrees C with 500 microM dehydroascorbic acid and energy
      substrates maintained ascorbate concentrations more than twice those observed in
      the absence of substrate. Succinate-dependent mitochondrial reduction of
      dehydroascorbic acid was blocked by inhibitors of mitochondrial Complexes II and
      III. Neither cytochrome c nor the outer mitochondrial membrane were necessary for
      the effect. The ascorbate radical was generated by mitochondria during treatment
      with dehydroascorbic acid and was abolished by ferricyanide, which does not
      penetrate the mitochondrial inner membrane. Together, these results show that
      energy substrate-dependent ascorbate recycling from dehydroascorbic acid involves
      an externally exposed portion of mitochondrial complex III.

PMID- 12061808
TI  - Phosphoinositide 3-kinase mediates protein kinase C beta II mRNA destabilization
      in rat A10 smooth muscle cell cultures exposed to high glucose.
AB  - High-glucose exposure down-regulates protein kinaseC beta II
      posttranscriptionally in rat and human vascular smooth muscle cells and
      contributes to increased cell proliferation. High-glucose-induced mRNA
      destabilization is specific for PKC beta II mRNA, while PKC beta I and other PKC
      mRNA are not affected. This study focused on whether glucose metabolism was
      required. The effect was blocked by cytochalasin B, suggesting a requirement for
      glucose uptake. Glucosamine did not mimic the effect, indicating that metabolism
      via hexosamine pathway was not involved. The effect was hexokinase-independent
      since 3-O-methylglucose, in a dose-dependent manner, mimicked high-glucose
      effects. Cycloheximide did not block the effect excluding dependency on new
      protein synthesis. Wortmannin and LY294002, phosphoinositide 3-kinase (PI3
      kinase) inhibitors, blocked glucose effects in the presence of 5,6-dichloro-1
      beta-d-ribofuranosylbenzimidazole. Glucose and 3-O-methylglucose activated PI3
      kinase, and LY294002 blocked glucose effects on Akt phosphorylation. In these
      cells, high-glucose concentrations activated a metabolically linked signaling
      pathway independent of glucose metabolism to regulate mRNA processing.

PMID- 12061810
TI  - Age-related changes in the composition and mechanical properties of human nasal
      cartilage.
AB  - Nasal cartilage is widely used in reconstructive surgery for the replacement of
      soft tissue defects and nasal reconstruction procedures. The ability to shape
      harvested tissue and the performance in the transplant site are related to the
      mechanical properties of nasal cartilage. Several studies have documented changes
      in composition and mechanical properties of other cartilages with age, but little
      is known about these processes in nasal cartilage. In this study, 45 human nasal
      septum specimens were gathered from patients 15-60 years of age after
      reconstructive surgery. Samples were cut to 6 mm in diameter and tested in
      confined compression to determine equilibrium modulus and hydraulic permeability
      and analyzed for glycosaminoglycan and hydroxyproline content. Equilibrium
      modulus decreased significantly with increasing donor age (P<0.01) while
      hydraulic permeability increased significantly (P<0.02). Glycosaminoglycan (GAG)
      content decreased significantly with age (P<0.05), while hydroxyproline content
      showed a slight, but not significant, increase with age (P>0.2). These trends are
      qualitatively similar to those observed in articular cartilage, suggesting the
      existence of a systemic process of cartilage degradation that is independent of
      mechanical loading. Further, the relationships between biochemical composition
      and mechanical properties were age-dependent, with cartilage from patients less
      than 30 years of age showing greater dependence of equilibrium modulus and
      hydraulic permeability on GAG and hydroxyproline content. This suggests that
      changes in matrix organization may accompany changes in tissue composition.

PMID- 12061809
TI  - Allosterically linked noncompetitive antagonist binding sites in the resting
      nicotinic acetylcholine receptor ion channel.
AB  - Previous studies have established the presence of overlapping binding sites for
      the noncompetitive antagonists (NCAs) amobarbital, tetracaine, and 3
      trifluoromethyl-3-(m-[(125)I]iodophenyl) diazirine ([(125)I]TID) within the ion
      channel of the Torpedo nicotinic acetylcholine receptor (AChR) in the resting
      state. These well-characterized NCAs and competitive radioligand binding and
      photolabeling experiments were employed to better characterize the interaction of
      the dissociative anesthetics ketamine and thienylcycloexylpiperidine (TCP) with
      the resting AChR. Our experiments yielded what appear to be conflicting results:
      (i) both ketamine and TCP potentiated [(125)I]TID photoincorporation into AChR
      subunits; and (ii) ketamine and TCP had very little effect on [(14)C]amobarbital
      binding. Nevertheless, (iii) both ketamine and TCP completely displaced
      [(3)H]tetracaine binding (K(i)s approximately 20.9 and 2.0 microM, respectively)
      by a mutually exclusive mechanism. To reconcile these results we propose that, in
      the resting ion channel, TCP and ketamine bind to a site that is spatially
      distinct from the TID and barbiturate locus, while tetracaine bridges both
      binding sites.

PMID- 12061811
TI  - Protein thiyl radicals directly observed by EPR spectroscopy.

PMID- 12061813
TI  - Nuclear apoptosis detection by flow cytometry: influence of endogenous
      endonucleases.
AB  - Nuclear apoptosis is characterized by chromatin condensation and progressive DNA
      cleavage into high-molecular-weight fragments and oligonucleosomes. These complex
      phenomena can be mediated by the activation of a multiplicity of enzymes,
      characterized by specific patterns of cation dependance, pH requirement, and mode
      of activation. The significance of this multiplicity of enzymes that cleave
      genomic DNA has been attributed to the need of death effector pathways specific
      for cell types/tissues, the level of cell differenciation, and the nature of the
      apoptotic stimuli. The activation of these factors contributes to the development
      of alterations that can be detected specifically by flow cytometric assays,
      namely, propidium iodide assays, acridine orange/ethidium bromide double
      staining, the TUNEL and ISNT techniques, and the assays of DNA sensitivity to
      denaturation. Although applicable to a wide spectrum of cell types, an increasing
      body of literature indicates that these techniques cannot be universally applied
      to all cell lines and apoptotic conditions: The requirement of a particular
      mediator(s) of nuclear apoptosis or the absence of endonuclease activity can
      limit the relevance of certain techniques. Finally, endonucleases recruited
      during primary necrosis can introduce nuclear alterations detected by some assays
      and raise the problem of their specificity. This review underlines the need for
      strategies to accurately detect and quantify nuclear apoptosis by flow cytometry
      when new cell systems and apoptotic conditions are considered.

PMID- 12061812
TI  - Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase
      derived from a trifunctional methylenetetrahydrofolate dehydrogenase
      cyclohydrolase-synthetase.
AB  - We have isolated the cDNA and the gene encoding the murine cytoplasmic
      methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase
      formyltetrahydrofolate synthetase (DCS). Comparison of these sequences with the
      3'-untranslated region of the mitochondrial NAD(+)-dependent
      methylenetetrahydrofolate dehydrogenase-cyclohydrolase (mt-DC) revealed areas of
      significant homology. Both exon and intron sequences of the synthetase domain of
      DCS are homologous to sequences in the untranslated region of mt-DC. A similar
      comparison between the mt-DC and the DCS sequences of humans as well as
      Drosophila supports the conclusion that in higher eukaryotes the bifunctional mt
      DC replaced a trifunctional precursor through inactivation of the synthetase
      domain. The mt-DC should be considered in models of one-carbon folate fluxes in
      mammals.

PMID- 12061814
TI  - The effector phase of physiological cell death relies exclusively on the
      posttranslational activation of resident components.
AB  - Inhibitors of transcription and translation can protect cells from physiological
      cell deaths induced by a variety of stimuli. These observations have been taken
      to suggest that de novo macromolecular synthesis may be an essential component of
      the cell death process. Paradoxically, the same inhibitors, at higher
      concentrations, themselves trigger the death of cells. Previously, we have mapped
      a conserved and ordered sequence of events that exerts physiological cell death.
      Diverse signals converge to activate this lethal pathway, composed of a
      proteolytic cascade of caspases and subsequent cyclin-dependent kinases. Here we
      report that inhibitors of nuclear gene expression, when they block cell death,
      act upstream of this lethal process to prevent its activation. In contrast, when
      cell death is triggered by high doses of the inhibitors, these same essential
      molecules are activated, despite the essentially complete blockade of
      macromolecular synthesis. This inhibitor-induced death response is associated
      with the release of cytochrome c from mitochondria and the activation of apical
      caspase 9 and is blocked by overexpression of Bcl-2. These data demonstrate that
      all essential molecules that exert lethality already are resident within cells
      and are activated posttranslationally upon stimulation. De novo macromolecular
      synthesis pertains idiosyncratically only to upstream, modulatory elements of
      particular death responses.

PMID- 12061816
TI  - Dynamics of chromosome compaction during mitosis.
AB  - We have quantitatively studied the space-time dynamics of mitotic chromosome
      compaction in cultured amphibian cells. After collecting digital phase-contrast
      images we have done digital image analysis to study spatial correlations in
      density. We find a characteristic distance at which the strongest correlations
      occur, which provides a quantitative measure of the size of patches of dense
      chromatin during interphase and early prophase. Later in mitosis, this length
      corresponds to the thickness of prophase and metaphase chromosomes. We find that
      during interphase strong correlations exist at a few-micrometer length; during
      prophase this correlation length progressively drops as the chromosomes are
      compacted. Our data are explained by a model based on assembly of chromatin loops
      onto already fiberlike interphase chromosomes. To test this model we have
      microinjected cobalt hexamine trichloride into interphase nuclei and have
      observed the rapid condensation of the interphase chromatin into thick fibers
      with a spacing similar to the native-state interphase correlation length
      determined from our image analysis.

PMID- 12061817
TI  - Possible interrelationship between changes in F-actin and myosin II, protein
      phosphorylation, and cell volume regulation in Ehrlich ascites tumor cells.
AB  - Osmotic shrinkage of Ehrlich ascites tumor cells (EATC) elicited translocation of
      myosin II from the cytosol to the cortical region, and swelling elicits
      concentration of myosin II in the Golgi region. Rho kinase and p38 both appeared
      to be involved in shrinkage-induced myosin II reorganization. In contrast, the
      previously reported shrinkage-induced actin polymerization [Pedersen et al.
      (1999) Exp. Cell Res. 252, 63-74] was independent of Rho kinase, p38, myosin
      light chain kinase (MLCK), and protein kinase C (PKC), which thus do not exert
      their effects on the shrinkage-activated transporters via effects on F-actin. The
      subsequent F-actin depolymerization, however, appeared MLCK- and PKC-dependent,
      and the initial swelling-induced F-actin depolymerization was MLCK-dependent;
      both effects were apparently secondary to kinase-mediated effects on cell volume
      changes. NHE1 in EATC is activated both by osmotic shrinkage and by the
      serine/threonine phosphatase inhibitor Calyculin A (CL-A). Both stimuli caused
      Rho kinase-dependent myosin II relocation to the cortical cytoplasm, but in
      contrast to the shrinkage-induced F-actin polymerization, CL-A treatment elicited
      a slight F-actin depolymerization. Moreover, Rho kinase inhibition did not
      significantly affect NHE1 activation, neither by shrinkage nor by CL-A.
      Implications for the possible interrelationship between changes in F-actin and
      myosin II, protein phosphorylation, and cell volume regulation are discussed.

PMID- 12061818
TI  - A subpopulation of murine bone marrow cells fully differentiates along the
      myogenic pathway and participates in muscle repair in the mdx dystrophic mouse.
AB  - Bone marrow (BM) transplantation in mice suggests the existence of pluripotent
      cells able to differentiate into skeletal muscle tissue, although sustained
      myofiber reconstitution has not yet been achieved. We investigated the myogenic
      potential of mouse BM cells and evaluated whether a BM fraction enriched for
      cells expressing skeletal muscle markers would ameliorate muscle repair, when
      compared to whole BM, into the dystrophic mdx mouse. We demonstrate that cells
      expressing striated-muscle-specific proteins are already present in the BM
      independently from experimentally forced myogenic conversion. We observed the
      presence of both markers of early myogenic program such as Pax3, Myf5, MyoD,
      desmin, and late myogenesis such as myosin heavy chain and alpha-sarcomeric
      actin. These myogenic cells are more represented in the early nonadherent BM
      fraction, which generates clones able to fully differentiate into myotubes.
      Transplantation in mdx mice by intravenous injection of whole BM and a tenfold BM
      myogenic enriched fraction resulted in BM reconstitution and limited dystrophin
      restoration. Taken together, these data show that a fraction of BM cells have a
      definite potential for differentiation along the skeletal muscle pathway and can
      be recruited by muscle repair mechanisms. They also indicate that factors
      limiting the degree of muscle recruitment and the host stem cell competition
      should be assessed in order to evaluate the usefulness of BM-derived myogenic
      cells into the context of cell-mediated gene therapy of inherited muscle
      diseases.

PMID- 12061815
TI  - The histone deacetylase inhibitor sodium butyrate interacts synergistically with
      phorbol myristate acetate (PMA) to induce mitochondrial damage and apoptosis in
      human myeloid leukemia cells through a tumor necrosis factor-alpha-mediated
      process.
AB  - Interactions between the histone deacetylase inhibitor sodium butyrate (SB) and
      phorbol 12-myristate 13-acetate (PMA) were examined in human myeloid leukemia
      cells (U937 and HL-60). Exposure of U937 cells to 1 mM SB and 1 nM PMA (24 h)
      markedly induced caspase activation and apoptosis, events accompanied by impaired
      differentiation induction (e.g., reduced plastic adherence and diminished
      expression of CD11b) as well as reduced clonogenic survival. The PKC inhibitor
      GF109203X blocked SB-/PMA-mediated apoptosis. Comparable results were obtained in
      HL-60 cells. Apoptosis was associated with early procaspase 8 activation and Bid
      cleavage, accompanied by pronounced mitochondrial damage (e.g., loss of
      mitochondrial membrane potential (DeltaPsi(m)) and cytochrome c release).
      Neutralization of endogenous TNFalpha by a human soluble TNF receptor
      substantially blocked SB-/PMA-induced cytochrome c release and apoptosis.
      Consistent with this, ectopic expression of a mutant dominant-negative caspase 8
      or CrmA resulted in a significant decrease in SB-/PMA-induced apoptosis, whereas
      Bcl-2 overexpression did not. SB/PMA treatment also triggered a decline in the S
      and G(2)M populations, and dephosphorylation of p34(cdc2). These results indicate
      that SB interacts with low concentrations of PMA to induce apoptosis in human
      leukemia cells and that this process proceeds through a PKC-/TNFalpha-dependent
      pathway in which procaspase 8 and Bid activation play key roles.

PMID- 12061819
TI  - EGF-dependent association of phospholipase C-gamma1 with c-Cbl.
AB  - The structure of phospholipase Cgamma1 (PLC-gamma1) contains two SH2 domains and
      one SH3 domain. While the function of the SH2 domains in PLC-gamma1 are well
      described, to date no growth factor-dependent function for the SH3 domain has
      been presented. To assess SH3 domain function in the context of the full-length
      PLC-gamma1, this domain was deleted and the mutant was stably expressed in Plcg1
      null mouse embryonic fibroblasts. Following EGF treatment of cells, the PLC
      gamma1DeltaSH3 mutant displayed the same increased level of tyrosine
      phosphorylation and association with EGF receptor as wild-type PLC-gamma1. Also,
      the SH3 mutant demonstrated membrane translocation and mediated the mobilization
      of intracellular Ca(2+) in response to EGF. c-Cbl is shown to associate with
      tyrosine phosphorylated PLC-gamma1 in an EGF-dependent manner, but no association
      was detected with the PLC-gamma1DeltaSH3 mutant. Interestingly, PDGF, which also
      tyrosine phosphorylates PLC-gamma1, failed to induce c-Cbl association with PLC
      gamma1 and also provoked no c-Cbl tyrosine phosphorylation. This suggests that c
      Cbl tyrosine phosphorylation is necessary for its interaction with PLC-gamma1.
      Evidence of a direct association of c-Cbl with PLC-gamma1 was provided by pull
      down and overlay experiments, using glutathione S-transferase fusion proteins
      that contain the SH3 domain of PLC-gamma1. The data, therefore, show an EGF
      inducible direct association of PLC-gamma1 with c-Cbl in vivo that is mediated by
      the SH3 domain of PLC-gamma1.

PMID- 12061820
TI  - Identification of cell binding sites in the laminin alpha5-chain G domain.
AB  - The laminins consist of at least 11 polypeptides (5 alpha-chains, 3 beta-chains,
      and 3 gamma-chains) specific to basement membranes. Here we investigate the
      biological activity associated with the G domain of the newly identified laminin
      alpha5-chain using 113 overlapping synthetic peptides (positions 2679-3635).
      Using HT-1080 cells, 21 peptides showed attachment activity either on peptide
      coated tissue culture plates or to peptide-conjugated Sepharose beads. Heparin
      inhibited cell attachment to 16 peptides, while ethylenediaminetetraacetic acid
      exhibited no inhibitory activity. Peptides A5G-27, A5G-65, and A5G-71 showed the
      strongest cell attachment, with the minimum active core sequences of the peptides
      being GIIFFL, HQNMGSVNVSV, and YLQFVG, respectively. Furthermore, these 16
      peptides were tested for their ability to stimulate neurite outgrowth in the PC12
      cells. A5G-3, A5G-33, A5G-71, A5G-73, A5G-81, and A5G-101 were the only peptides
      of the 16 that demonstrated the ability to promote neurite outgrowth. These
      results demonstrate that synthetic peptides with alpha5-chain G domain primary
      amino acid sequences possess some of the same biological activities attributable
      to the whole laminin and the alpha5-chain G domain. Therefore, these peptides may
      be useful in the investigation of laminin-receptor interactions and possibly
      mechanisms of laminin signal transduction.

PMID- 12061821
TI  - Regulation of Id1 protein expression in mouse embryo fibroblasts by the type 1
      insulin-like growth factor receptor.
AB  - The activated type 1 insulin-like growth factor (IGF-IR) increases the expression
      of Id1 proteins in mouse embryo fibroblasts (MEF). Up-regulation depends on a
      functional receptor and on multiple pathways originating from different domains
      of the receptor. In MEF, Id1 protein expression is also up-regulated by serum and
      certain oncogenes. Signaling through Stat3 plays an important, but not exclusive,
      role in the up-regulation of Id1 protein levels. In all instances, the increase
      in Id1 protein expression is paralleled by a corresponding increase in Id1
      promoter activity, as measured with a reporter gene.

PMID- 12061822
TI  - Spontaneous reversion of tsBN67 cell proliferation and cytokinesis defects in the
      absence of HCF-1 function.
AB  - Mammalian HCF-1 is a highly conserved and abundant chromatin-bound protein that
      plays a role in both herpes simplex virus (HSV) immediate-early (IE) gene
      transcription and cell proliferation. Its role in cell proliferation has been
      evidenced through the analysis of a temperature-sensitive hamster cell line
      called tsBN67. When placed at nonpermissive temperature, tsBN67 cells undergo a
      stable and reversible proliferation arrest after a lag of 36-48 h. This phenotype
      results from a single point mutation in HCF-1, which disrupts HCF-1 association
      with both chromatin and the HSV IE transactivator VP16 at nonpermissive
      temperature. Here, we report the isolation and characterization of spontaneous
      tsBN67 growth-revertant cells that are able to proliferate at nonpermissive
      temperatures. These cells retain the tsBN67 HCF-1 point mutation and grow in the
      absence of HCF-1 chromatin association, demonstrating that complete restoration
      of tsBN67 HCF-1 functions is not essential for cell proliferation. Phenotypic
      analysis of both mutant and revertant tsBN67 cells shows that, in addition to a
      cell proliferation defect, these cells display a conspicuous multinucleated
      phenotype in a significant population of arrested cells. This defect in
      cytokinesis is also a result of loss of HCF-1 function, suggesting that HCF-1
      plays a role in cell exit from mitosis. The revertant tsBN67 cells display a
      coincident restoration of cell proliferation and suppression of the cytokinetic
      defect, suggesting that HCF-1 plays a shared role in cell proliferation and
      cytokinesis.

PMID- 12061823
TI  - Gill tissue recovery after copper exposure and blood parameter responses in the
      tropical fish Prochilodus scrofa.
AB  - Changes in Prochilodus scrofa gill tissue and in blood responses were
      investigated after 96-h copper exposure and transference to clean water. Gill
      damage was characterized by epithelial lifting, cell swelling, pavement, chloride
      and mucous cell proliferation, and blood vessel anomalies. Restoration of gill
      structure was slow, with no tissue improvements in the first 2 days in clean
      water. From the 7th to the 15th day, the recovery of gill tissue began to become
      evident, with complete recovery occurring on the 45th day in clean water.
      Hematocrit, red blood cells, and hemoglobin concentration showed a significant
      increase after copper exposure, remaining high until the 7th day after
      transference to clean water. Plasma Na(+) and Cl(-) concentration decreased
      significantly and K(+) increased significantly after copper exposure and, on the
      7th day in clean water, plasma ions showed no significant difference from those
      in control fish. Gill tissue restoration took longer than the recovery of blood
      parameters, possibly implying extra energy needs, which may be critical,
      depending on the fish's life cycle.

PMID- 12061824
TI  - Removal of toxic metals from leachates from hazardous solid wastes and reduction
      of toxicity to microtox by the use of calcium alginate beads containing humic
      acid.
AB  - Improper disposal of hazardous wastes can lead to release of potentially harmful
      substances through leaching such as heavy metals, which ultimately contaminate
      soil, sediment surface water, and groundwater through runoff. To remove these
      toxic metals and avoid any adverse effect on the ecosystem, a novel approach
      involving calcium alginate (CA) beads containing humic acid (HA) was used. For
      this, 10% leachates of the waste obtained from two major industrial units with
      electroplating processess were prepared at neutral pH and analyzed by atomic
      absorption spectrophotometry (AAS). Both leachates contained Cd, Cu, Cr, Ni, Mn,
      Fe, and Zn. The concentrations of Ni, Mn, Fe, and Zn in the waste were found to
      be significant. The leachates analyzed were passed through columns packed with
      calcium alginate beads with or without humic acid. The concentrations of various
      metals in beads and in different fractions collected after adsorption were
      measured. Data recorded indicate that calcium alginate beads containing humic
      acids are more efficient in removal of all metals in substantial amounts from the
      two leachates. Along with removal of metals, this process led to considerable
      detoxification of the leachates as tested by Microtox assay, indicated by earlier
      protection and higher EC(50). The significance of the results in relation to
      removal of toxic metals by beads containing humic acid is discussed.

PMID- 12061825
TI  - Comparing sensitivity of ecotoxicological effect endpoints between laboratory and
      field.
AB  - Extrapolating toxicant effects with a fixed application factor (AF) approach or
      one of the species sensitivity distribution (SSD) models presumes that toxicant
      effects on single, individual-level endpoints reflect effects at the ecosystem
      level. Measured effect concentrations on plankton from multispecies field tests
      using tributyltin (TBT) and linear alkylbenzene sulfonates (LAS) were compared
      with published laboratory single-species test results and measured in situ
      concentrations. Extrapolation methods were evaluated by comparing predicted no
      effect concentrations (PNECs), calculated by AF and SSD models with NOECs and
      E(L)C(50)s obtained from field studies. Overall, structural parameters were more
      sensitive than functional ones. Measured effect concentrations covered
      approximately the same range between laboratory and field experiments. Both SSD
      and AF approaches provide PNECs that appear to be protective for ecosystems. The
      AF approach is simpler to apply than the SSD models and results in PNECs that are
      no less conservative. Calculated PNEC values and the lowest field effect
      concentrations were lower than measured environmental concentrations for both
      substances, indicating that they may pose a risk to marine ecosystems.

PMID- 12061826
TI  - Acute lethal toxicity of environmental pollutants to aquatic organisms.
AB  - The acute lethal toxicity of environment pollutants including chlorophenol,
      haloalkane, quinone, and substituted nitrobenzene (i.e., nitrophenol,
      nitrobenzene, nitrotoluene, and aniline) compounds to aquatic organisms was
      determined. Determination of toxicity of chemicals was performed with chlorella,
      daphnia, carp, and tilapia. The toxicity of chlorophenols had no relation to the
      number of chlorine atoms on the benzene ring, but monochlorophenol had lower
      activity than more chlorine-substituted compounds. The tolerance levels of
      daphnia and carp to haloalkanes was found to be higher than that of chlorella;
      toxicity to chlorella was several hundred times higher than to daphnia. The
      toxicity of naphthoquinone compounds to chlorella and carp was higher than that
      of anthraquinone. A compound with a monochloride substitution on anthraquinone
      ring was less toxic to carp than those substituted with amine, hydroxyl, and
      dichlorine groups. Nitrobenzene compounds with an additional substitution group
      on the p position were extremely toxic to daphnia and carp.

PMID- 12061827
TI  - Effect of mercury on general and reproductive health of largemouth bass
      (Micropterus salmoides) from three lakes in New Jersey.
AB  - The influence of mercury on the general and reproductive health of wild fish
      populations has not been well studied. Therefore, a variety of health and
      reproductive indicators were measured in male largemouth bass (Micropterus
      salmoides) collected from three bodies of water in New Jersey: Assunpink Lake,
      Manasquan Reservoir, and Atlantic City Reservoir. The mean mercury content in
      fish muscle from Assunpink Lake was 0.30 microg/g; from Manasquan Reservoir, 1.23
      microg/g; and from Atlantic City Reservoir, 5.42 microg/g. Body weight, length,
      condition factor, and gonadosomatic index were similar for all three lakes.
      Furthermore, there was no significant relationship between muscle mercury content
      and adrenocortical function, indicated by interrenal nuclear diameter and serum
      cortisol levels following stress. Bass from the Atlantic City Reservoir had a
      slightly lower, although significant, liver somatic index than bass from the two
      other lakes. A significant, positive correlation between 11-ketotestosterone
      serum concentrations and mercury muscle content was detected, although no
      significant relationship between testosterone serum concentrations and mercury
      muscle content was found. The findings of this study suggest that, while elevated
      levels of mercury in fish potentially alter androgen profiles, they do not
      substantially decrease other indicators of general and reproductive health.

PMID- 12061828
TI  - A procedure for setting environmentally safe total maximum daily loads (TMDLs)
      for selenium.
AB  - This article presents a seven-step procedure for developing environmentally safe
      total maximum daily loads (TMDLs) for selenium. The need for this information
      stems from recent actions taken by the U.S. Environmental Protection Agency (EPA)
      that may require TMDLs for selenium and other contaminants that are impairing
      water bodies. However, there is no technical guidance from EPA or elsewhere that
      deals exclusively with selenium. This leaves biologists and environmental
      contaminant specialists without the tools needed to effectively address the TMDL
      issue for selenium. This article provides guidance by laying out an assessment
      method that links the basic components of EPA's TMDL process to the contaminant
      specific information required for selenium. The underlying principle in this
      process is that selenium concentrations be kept below levels that threaten
      reproduction of fish and aquatic birds. The steps are: (1) Delineate and
      characterize the hydrological unit (HU, i.e., water body) of interest. (2)
      Determine selenium concentrations and assess biological hazard. (3) Determine
      sources, concentrations, and volumes of selenium discharges; calculate existing
      selenium load. (4) Estimate retention capacity of HU for selenium. (5) Calculate
      the total allowable selenium load and specify reductions needed to meet the
      target loading. (6) Allocate selenium load among discharge sources. (7) Monitor
      to determine effectiveness of selenium load reduction in meeting environmental
      quality goals. Proper application of this procedure will ensure compliance with
      EPA regulatory requirements and also protect fish and wildlife resources.

PMID- 12061829
TI  - Effect of temperature and pirimiphos methyl on biochemical biomarkers in
      Chironomus riparius Meigen.
AB  - Fourth-instar Chironomus riparius Meigen larvae were exposed to the
      organophosphate (OP) insecticide pirimiphos methyl (0, 0.1, 1.0, and 10 microg/L)
      for 48, 72, or 96 h at three temperatures (3, 12, or 22 degrees C). Two
      biochemical biomarkers, acetylcholinesterase (AChE) and glutathione S-transferase
      (GST), were measured in individual larvae from each treatment. AChE activity was
      inhibited by the OP in a dose-responsive fashion. This response remained similar
      at all three temperatures, demonstrating that AChE is a robust and specific
      biomarker. Exposure duration had little effect on AChE activity. In contrast, GST
      activity was induced at the highest OP insecticide concentration, but induction
      was also evident at 3 degrees C. There was a significant effect of exposure
      duration, with an overall decline in GST activity over time. This result agrees
      with previous work suggesting that GSTs are not particularly suitable for use as
      a biomarker of pesticide exposure or effect in Chironomus.

PMID- 12061830
TI  - Effect of some organophosphorus pesticides on oxygen consumption of shrimp,
      Litopenaeus vannamei.
AB  - Oxygen consumption was measured in adult specimens of Litopenaeus vannamei
      shrimps from a coastal lagoon of Sinaloa, Mexico, during exposure to sublethal
      concentrations of the organophosphorus pesticides, Diazinon, Folidol, and
      Gusathion. Each individual was used as a control of itself, to avoid differences
      between treatments being masked by individual variability. In all three
      treatments with pesticides, respiration rate, measured by a polarographic
      electrode, was significantly lower than in controls. This may, at least partly,
      explain the decrease in shrimp production observed in recent years in the coastal
      lagoons of Sinaloa.

PMID- 12061831
TI  - Effect of Navy chaff release on aluminum levels in an area of the Chesapeake Bay.
AB  - The U.S. Navy uses aluminized glass chaff as a passive countermeasure for radar
      guided threats to aircraft and surface ships. Over the last 25 years, several
      hundred thousand pounds of aluminized chaff have been released during flight
      operations over a training area on the Chesapeake Bay. There is concern that
      these releases have resulted in the accumulation of significant amounts of
      aluminum in the soil and sediment of this training area. This study compares the
      exchangeable and monomeric aluminum content of sediment within the affected area
      with that of samples taken from outside the training area. We found a less than
      twofold increase in the content of organic monomeric aluminum in samples taken
      from the affected area versus background samples, whereas inorganic monomeric
      aluminum concentrations within the affected area were significantly lower than
      background. These results suggest that chaff releases have not resulted in a
      significant accumulation of aluminum in this training area.

PMID- 12061832
TI  - A case study of logistic QSAR modeling methods and robustness tests.
AB  - Acute toxicity (15-min EC(50)) determination of 16 substituted naphthalene
      compounds to Photobacterium phosphoreum was undertaken according to the standard
      procedures, while the effects of molecular structures of selected compounds on
      their toxicity to test microorganisms were logistically conducted using the
      quantitative structure-activity relationship (QSAR) technique. The relationship
      was developed as -log EC(50)=5.5916 (+/-0.1189)-7.4893(+/-0.4900)qH(+)+0.7771(+/
      0.0619E(lumo)+0.0088(+/-0.0009)alpha(N=16, R(2)(adj)=0.9698, SE=0.0892,
      P=0.0000). The cluster analyses of individual structure descriptors as well as
      the quality control chart and Monte Carlo simulation test indicated that the
      prediction model was reasonable and robust even if tested with several different
      methods. Furthermore, the quantum chemical parameters entering into the QSAR
      model were used to discuss the possible toxicity pathways, and the results
      revealed that the selected compounds were reactive and their toxicity behaviors
      were complex processes containing physical partition stages as well as
      biochemical reaction stages.

PMID- 12061833
TI  - Integration of aquatic fate and ecological responses to linear alkyl benzene
      sulfonate (LAS) in model stream ecosystems.
AB  - An integrated model stream ecosystem fate and effect study of dodecyl linear
      alkylbenzene sulfonate (C(12)LAS) was performed in the summer and fall of 1996.
      The study addressed responses of periphytic microbes, immature benthic fauna
      including abundance, drift, and emergence of adult insects in a 56-day exposure.
      Exposures ranged from 126 to 2978 microg/L and were continuously presented in a
      single-pass, flow-through test system. Microbial heterotrophs acclimated to
      C(12)LAS exposure quickly (14 days) and biodegraded C(12)LAS at all
      concentrations. Blue-green algae responded by increasing in abundance with
      increasing C(12)LAS concentration. Invertebrates responded by increased drift and
      reduced benthic abundances at concentrations exceeding 293 microg/L. Emergence at
      927 microg/L also declined relative to the control. Adverse responses for
      mayflies and chironomids were indicated using univariate statistical techniques.
      Multivariate techniques indicated these taxa plus mollusks, aquatic worms,
      caddisflies, and stoneflies were impaired at some concentrations. Bioavailability
      of C(12)LAS was investigated in streams as a function of the total suspended
      solid load in the water column driven by local weather and watershed patterns. A
      continuous bioavailability model indicated exposure was reduced by an average of
      8.5+/-8.9%. A model ecosystem no-observed-effect concentration (NOEC) was
      concluded to be 293 microg/L based on measured water column exposure and adjusted
      to 268 microg/L by the bioavailability model. A literature review of 13 available
      model ecosystem studies was conducted and NOEC conclusions were adjusted by a
      structure-activity relationship to a dodecyl chain length (sulfophenyl position
      and distribution being ignored due to lack of information in the reviewed
      studies). Lentic studies (n=7) were found to have higher NOECs than lotic studies
      (n=6) and were more variable. Mean NOECs+/-SD for all studies, lentic studies
      only, and lotic studies only were 3320+/-6040, 5720+/-7640, and 530+/-430
      microg/L, respectively. Interpretation of results for anomalies from specific
      studies suggests the importance of experimental design, use of laboratory versus
      natural surface water, biological complexity of the test system, and physical
      test system design as relevant factors for consideration. The specific results of
      the new model ecosystem study presented in this article can be well defended on
      the basis of a robust experimental and physical design and because the system
      contained a diverse and sensitive aquatic community. A low or no uncertainty
      factor could be applied to the result.

PMID- 12061835
TI  - Thiol antioxidants inhibit the formation of the interleukin-12 heterodimer: a
      novel mechanism for the inhibition of IL-12 production.
AB  - IL-12 is a 75 kDa heterodimeric cytokine composed of two disulfide-linked
      subunits, p35 and p40, which plays an important role in the regulation of the
      immune response. We tested the hypothesis that thiol antioxidants might interfere
      with dimerization of the two IL-12 subunits. We thus studied the effect of
      reduced glutathione (GSH) and N-acetyl-cysteine (NAC) on IL-12 p75 production by
      human THP-1 cell stimulated with IFN-gamma and Staphylococcus aureus Cowan strain
      I (SAC), using ELISAs specific for IL-12 p75 or the p40 subunit. NAC and GSH, but
      not cystine, at concentrations of 5-10 mM inhibited production of IL-12 p75 but
      not of the p40 subunit. NAC did not inhibit p40 or p35 mRNA expression in
      dendritic cells or THP-1 cells, or NF-kappa B activation in THP-1 cells. The
      effect of NAC was specific for IL-12 p75, as NAC did not affect induction of MHC
      class II expression by IFN-gamma-stimulated THP-1 cells. IL-12 dimer formation
      appears to be reduced by NAC also in vivo, because pretreatment with NAC (1 g/kg,
      orally), before LPS injection in mice, inhibited peak IL-12 p75 serum levels
      without affecting those of p40. We conclude that thiol levels regulate IL-12 p75
      production and that assembly of the heterodimer is a step that might represent a
      target for pharmacological intervention.

PMID- 12061836
TI  - Differential effects between marimastat, a TNF-alpha converting enzyme inhibitor,
      and anti-TNF-alpha antibody on murine models for sepsis and arthritis.
AB  - We investigated the effects of marimastat, an inhibitor of TNF-alpha converting
      enzyme and matrix metalloproteinases, and anti-TNF-alpha antibodies on a murine
      model for sepsis, and on arthritis in human TNF-alpha transgenic mice. Marimastat
      (25-200 mg/kg) inhibited lipopolysaccharide (LPS)-induced soluble TNF-alpha
      production in mice in a dose-dependent manner. At an oral dose of 200 mg/kg,
      marimastat almost completely inhibited LPS-induced soluble TNF-alpha production,
      but only slightly delayed LPS lethality. On the other hand, anti-TNF-alpha
      antibodies completely abolished LPS-induced morbidity. In addition, anti-TNF
      alpha antibodies, but not marimastat (200 mg/kg/day), inhibited the development
      of arthritis in human TNF-alpha transgenic mice. These results suggest that cell
      surface TNF-alpha may be important in the pathogenesis of murine models for
      sepsis and arthritis.

PMID- 12061837
TI  - Recombinant TNF-alpha mediated regulation of the I kappa B-alpha/NF-kappa B
      signaling pathway: evidence for the enhancement of pro- and anti-inflammatory
      cytokines in alveolar epithelial cells.
AB  - The signaling transduction mechanism mediated by tumor necrosis factor-alpha (TNF
      alpha) in the alveolar epithelium is not well characterized. It was subsequently
      hypothesized that recombinant murine TNF-alpha (rmTNF-alpha) selectively
      regulates the inhibitory kappa B (I kappa B-alpha)/nuclear factor-kappa B (NF
      kappa B) pathway and interferes with the endogenous biosynthesis of pro
      inflammatory (stimulatory) and anti-inflammatory (inhibitory) cytokines. The
      cytokine rmTNF-alpha induced, in a time- and dose-dependent manner, the
      degradation of I kappa B-alpha within the cytosolic compartment, an effect
      associated with up-regulating its phosphorylation. This allowed the biphasic
      regulation of selective NF-kappa B subunit nuclear translocation, thereby
      mediating a dual excitatory mechanism on NF-kappa B activation. The
      immunoregulatory effect of rmTNF-alpha was associated with a time-dependent
      induction of pro-inflammatory [interleukin (IL)-1 beta, IL-6 and TNF-alpha] and
      anti-inflammatory (IL-10) cytokine biosynthesis. These results indicate a novel
      involvement of an I kappa B-alpha/NF-kappa B-sensitive pathway mediating the
      effect of TNF-alpha, which is associated with an autocrine, endogenous mechanism
      mediating the regulation of cytokine signaling.

PMID- 12061838
TI  - Collagens, collagen-binding heat shock protein 47 and transforming growth factor
      beta 1 are induced in cicatricial pemphigoid: possible role(s) in dermal
      fibrosis.
AB  - Cicatricial pemphigoid (CP) is an autoimmune mucocutaneous blistering disease
      associated with scarring. Heat shock protein 47 (HSP47) is thought to play an
      important role in fibrogenesis, but its role in skin lesions of cicatricial
      pemphigoid is not yet known. In the present study, we examined the role of HSP47
      in dermal fibrosis in cutaneous lesions of a CP patient. Skin biopsies from a
      patient with CP, and from normal subjects were studied for the expression of
      HSP47, and interstitial collagens (type I and type III collagens) by
      immunohistochemistry. Dermal fibroblasts isolated from skin of normal individuals
      and from fibrotic skin of a CP patient were used to study the expression of
      HSP47, transforming growth factor beta 1 (TGF-beta 1), type I and type III
      collagens. Compared to the control skin sections, an increased expression of
      HSP47 was associated with an increased deposition of interstitial collagens in
      the fibrotic skin section of the CP patient. Similarly, in contrast to control
      dermal fibroblasts, the fibroblasts isolated and cultured from fibrotic skin of
      the CP patient, and grown in vitro, exhibited increased expression of HSP47, type
      I and type III collagens. Furthermore, compared to the normal control
      fibroblasts, an increased expression of TGF-beta 1 was detected in the dermal
      fibroblasts isolated from fibrotic skin of the CP patient. When dermal
      fibroblasts were treated with various concentrations of TGF-beta 1 (6.25, 12.5,
      25, 50 and 100 ng/ml for 24 h), it induced the expression of both type I collagen
      and HSP47, as determined by quantitative real-time PCR. In conclusion, the
      expression of TGF-beta 1, HSP47, type I collagen and type III collagen was up
      regulated in the fibrotic skin of CP patient, and a complex interaction of these
      molecules may initiate and propagate the fibrotic cascade in the skin of CP
      patients.

PMID- 12061839
TI  - Regulation of human eotaxin-3/CCL26 expression: modulation by cytokines and
      glucocorticoids.
AB  - Eotaxin-3 (CCL26) is a CC chemokine that signals exclusively via the CCR3
      receptor and has eosinophil-selective chemoattractant activity. Comparison of
      Eotaxin-1 (CCL11) and Eotaxin-2 (CCL24), demonstrates differences in their
      expression profiles, cell specificity and effector kinetics, implying distinct
      biological actions. But little data in this regard have been reported for Eotaxin
      3. We aimed to analyse the effect of Th2 cytokines and glucocorticoids on Eotaxin
      3 mRNA expression in human lung epithelial cells and dermal fibroblasts; cells
      implicated in the pathogenesis of allergic asthma and allergic dermatitis
      respectively. Eotaxin-3 mRNA levels in primary dermal fibroblasts and NCI-H727
      lung epithelial cells were determined by Northern hybridization. In contrast to
      Eotaxin-1, Eotaxin-3 mRNA expression was not detected in unstimulated cells. The
      Th2 cytokines IL-4 and IL-13 induced Eotaxin-3 expression in a time and dose
      dependent manner, with IL-4 demonstrating a 100-fold greater potency. Unlike
      Eotaxin-1, Eotaxin-3 mRNA expression was not induced by either tumour necrosis
      factor (TNF)-alpha or interleukin (IL)-1 beta alone. Both IL-4 and IL-13 acted
      synergistically with TNF-alpha in superinducing Eotaxin-3 mRNA expression.
      Dexamethasone pre-treatment diminished induction of Eotaxin-3 mRNA expression. We
      conclude that modulation of Eotaxin-3 mRNA expression by Th(2) cytokines is
      different from that of Eotaxin-1 and Eotaxin-2, further supporting a distinct
      biological role for Eotaxin-3.

PMID- 12061840
TI  - Coexpression of oncostatin M and its receptors and evidence for STAT3 activation
      in human ovarian carcinomas.
AB  - The expression of oncostatin M and leukemia inhibitory factor (LIF), JAK-STAT
      activators and members of the interleukin-6 family of cytokines, were examined in
      a series of primary ovarian carcinomas using immunohistochemistry. The malignant
      epithelial cells of all 29 ovarian carcinomas examined expressed oncostatin M;
      none expressed LIF. Oncostatin M can activate two related receptors, one
      consisting of a low-affinity LIF receptor subunit, LIFR beta, which forms a
      heterocomplex with the gp130 signal transducing protein and can recognize both
      oncostatin M and LIF, and a second heterocomplex consisting of a subunit that
      specifically recognizes oncostatin M, OSMR beta, and the gp130 protein. By
      immunohistochemistry, 25 of 25 ovarian carcinomas examined expressed the LIFR
      beta subunit in the malignant epithelial cells (all samples express gp130), and
      two-thirds the ovarian carcinomas studied expressed OSMR beta mRNA as determined
      by RT-PCR. Thus oncostatin M and its receptors are commonly coexpressed in
      malignant ovarian epithelial cells, and represent a potential autocrine loop in
      this tumor type. STAT3, of one the signaling proteins downstream of the
      oncostatin M/LIF receptors, was found in its phosphorylated, activated form
      (phosphotyrosine 705 STAT3) in the malignant epithelial cells of 17 of 23 ovarian
      carcinomas examined (74%) as determined by immunohistochemistry; this suggests
      that this protein is constitutively activated in most ovarian carcinomas, as it
      is in many other human malignancies. Recombinant human Oncostatin M (rhOSM) can
      induce the transient tyrosine 705 phosphorylation of STAT3 in serum-starved LIFR
      beta/OSMR beta expressing ovarian carcinoma cell lines, but does not alter cell
      growth and effects only a modest increase in the apoptotic rate in these cultured
      cells. Oncostatin M and its receptors may be part of a network of cytokine
      systems within ovarian carcinomas that may act to maintain STAT3 in its activated
      form, a phenomenon associated with the malignant phenotype.

PMID- 12061841
TI  - Oncostatin M production by human dendritic cells in response to bacterial
      products.
AB  - Oncostatin M (OSM) is a pleiomorphic cytokine that belongs to the IL-6 cytokine
      family. It is produced by activated T cells and monocytes/macrophages and plays
      an important role in the process of inflammatory responses. Although dendritic
      cells (DCs) have been shown to secrete a variety of cytokines, it is not
      elucidated whether DCs are able to produce OSM. To clarify this, using human DCs
      derived from peripheral blood cells, we measured the protein levels of OSM in the
      supernatants of DC cultures by ELISA and examined the expression of OSM mRNA by
      RT-PCR after stimulation with lipopolysaccharide (LPS) or fixed Staphylococcus
      aureus (SACS). Upon stimulation with bacterial products, DCs secreted a large
      amount of OSM protein in a dose- and time-dependent manner. Concomitantly, the
      expression of OSM mRNA by DCs was markedly up-regulated. Compared the ability of
      DCs to produce OSM with that of monocytes, which are major producers of OSM, DCs
      released significantly higher amounts of OSM protein in the culture supernatants
      than monocytes. These findings indicate for the first time that human monocyte
      derived DCs can synthesize and secrete large amounts of OSM in response to
      bacterial products, suggesting that OSM produced by DCs at infectious sites may
      play a role in modulating inflammatory responses.

PMID- 12061843
TI  - Fetal development of mouse oocytes and zygotes cryopreserved in a nonconventional
      freezing medium.
AB  - This study (1) analyzed fetal development of mouse embryos after oocyte
      cryopreservation in CJ2, a choline-based medium, (2) examined the effect of
      culture duration in vitro on subsequent fetal development, and (3) compared
      survival and fetal development of zygotes frozen in embryo transfer freeze medium
      (ETFM; sodium-based medium) or CJ2. Unfertilized oocytes and zygotes were
      cryopreserved using a slow-cooling protocol. After thawing, oocytes were
      inseminated after drilling a hole in their zona, cultured in vitro either to the
      two-cell or blastocyst stage, and transferred to the oviducts or uterine horns of
      recipient mice. In parallel experiments, frozen-thawed zygotes were similarly
      cultured and transferred. Implantation rates for transferred embryos were high
      (range 66-88%), regardless of whether they had been frozen as oocytes or zygotes
      and whether they had been transferred to the oviduct or uterus. However, fetal
      development was significantly higher when two-cell embryos were transferred. With
      blastocyst transfer, control embryos implanted and produced a greater proportion
      of fetuses than did oocytes frozen in CJ2, whereas transfer at the two-cell stage
      resulted in similar proportions of implantation sites and fetuses. Blastocyst
      transfer of zygotes cryopreserved in ETFM or CJ2 produced similar fetal
      development rates (23.6% vs 20.0%), but when frozen-thawed zygotes were
      transferred at the two-cell stage the fetal development rates were higher in the
      ETFM group (53.3%) than in the CJ2 group (32.0%). A high proportion (46.7%) of
      oocytes frozen in CJ2 in a nonprogrammable freezer and plunged at -20 degrees C
      developed into live offspring. This study shows that in the mouse (1) oocytes
      frozen in CJ2 can develop into viable fetuses, (2) prolonging culture in vitro
      has a detrimental effect on embryo transfer outcome, and (3) CJ2 offers no
      advantage for zygote cryopreservation.

PMID- 12061844
TI  - Inhibition of bacterial ice nucleation by polyglycerol polymers.
AB  - The simple linear polymer polyglycerol (PGL) was found to apparently bind and
      inhibit the ice nucleating activity of proteins from the ice nucleating bacterium
      Pseudomonas syringae. PGL of molecular mass 750 Da was added to a solution
      consisting of 1 ppm freeze-dried P. syringae 31A in water. Differential ice
      nucleator spectra were determined by measuring the distribution of freezing
      temperatures in a population of 98 drops of 1 microL volume. The mean freezing
      temperature was lowered from -6.8 degrees C (control) to -8.0,-9.4,-12.5, and 
      13.4 degrees C for 0.001, 0.01, 0.1, and 1% w/w PGL concentrations, respectively
      (SE < 0.2 degrees C). PGL was found to be an ineffective inhibitor of seven
      defined organic ice nucleating agents, whereas the general ice nucleation
      inhibitor polyvinyl alcohol (PVA) was found to be effective against five of the
      seven. The activity of PGL therefore seems to be specific against bacterial ice
      nucleating protein. PGL alone was an ineffective inhibitor of ice nucleation in
      small volumes of environmental or laboratory water samples, suggesting that the
      numerical majority of ice nucleating contaminants in nature may be of
      nonbacterial origin. However, PGL was more effective than PVA at suppressing
      initial ice nucleation events in large volumes, suggesting a ubiquitous sparse
      background of bacterial ice nucleating proteins with high nucleation efficiency.
      The combination of PGL and PVA was particularly effective for reducing ice
      formation in solutions used for cryopreservation by vitrification.

PMID- 12061846
TI  - Cryopreservation of mantle dissociated cells from Haliotis tuberculata
      (Gastropoda) and postthawed primary cell cultures.
AB  - Dissociated mantle cells from the gastropod mollusc Haliotis tuberculata were
      cultured after a freezing-thawing procedure using either 10% dimethyl sulfoxide
      (Me(2)SO) or 10% glycerol (Gly) as a cryoprotector. The survival rate of 2-day
      old cultured cryopreserved cells after thawing, based on analysis of DNA and
      protein contents, was nearly 80% in comparison with 2-day-old cultured fresh
      cells. Cells thawed after cryopreservation exhibited the maintenance of all
      tested physiological activities. Metabolic activity (measured by the MTT test)
      and the activity of alkaline phosphatase (a plasma membrane-bound enzyme) were
      not decreased in comparison to those in cultured fresh cells. In addition,
      cryopreserved cultured cells maintained a physiological stimulation ability in
      response to treatment with growth factors. These results taken together represent
      one of the most convincing demonstrations of the survival and of the recovery of
      intact functional activities of molluscan cells after a freeze-thawing procedure.
      Our results suggest that in the future primary cultures of cryopreserved mantle
      cells will be able to be used for fundamental research, in toxicity tests, or in
      the field of biotechnology.

PMID- 12061845
TI  - Vitrification media: toxicity, permeability, and dielectric properties.
AB  - The aim of this study was to select a cryoprotectant for use in attempts to
      preserve tissues and organs by vitrification. The first step was to select a cell
      line with which to compare the toxicity of a range of commonly used
      cryoprotectants. An immortal vascular endothelial cell (ECV304) was exposed to
      vitrifying concentrations of four cryoprotectants: dimethyl sulfoxide (Me(2)SO;
      45% w/w); 2,3 butanediol (BD; 32%); 1,2-propanediol (PD; 45%); and ethanediol
      (ED; 45%). Three times of exposure (1, 3, and 9 min) and two temperatures (22 and
      2-4 degrees C) were studied. After removal of the cryoprotectant, the ability of
      the cells to adhere and divide in culture over a 2-day period was measured and
      expressed as a Cell Survival Index (CSI). There was no measurable loss of cells
      after exposure to the four cryoprotectants but 3-min exposure to BD, PD, or
      Me(2)SO at room temperature completely destroyed the ability of the cells to
      adhere and divide in culture. In contrast, exposure to all four cryoprotectants
      at 2-4 degrees C for up to 9 min permitted the retention of significant cell
      function, the CSIs, as a proportion of control, being 76.3+/-7.0% for BD, 63.6+/
      7.1% for PD, 37.0+/-4.1 for Me(2)SO, and 33.2+/-3.0 for ED. The permeability
      properties of the cells for these four cryoprotectants was also measured at each
      temperature. Permeability to water was high, L(p) approximately equal 10(-7)
      cm/s/atm at 2-4 degrees C with all the cryoprotectants, but there were
      substantial differences in solute permeability: BD and PD were the most permeable
      at 2-4 degrees C (P(s)=4.1 and 3.0 x 10(-6) cm/s, respectively). Equilibration of
      intracellular cryoprotectant concentration was rapid, due in part to high water
      permeability; the cells were approximately 80% of their physiological volume
      after 10 min. Treatment at 2-4 degrees C with BD was the least damaging, but PD
      was not significantly worse. Exposure to vitrifying concentrations of ED and
      Me(2)SO, even at 2-4 degrees C, was severely damaging. Segments of rabbit carotid
      artery were treated with vitrifying concentrations of each of the two most
      favorable cryoprotectants, BD and PD, for 9 min. It was shown that each
      cryoprotectant reduced smooth muscle maximum contractility to a similar extent
      and abolished the acetylcholine response. However, vital staining revealed that
      exposure to BD also caused substantial damage to the endothelial lining, whereas
      the endothelium was completely intact after PD exposure, raising the possibility
      that the effect of PD on NO release may be reversible. In later stages of this
      project it is planned to use dielectric heating to rewarm the tissues and thereby
      avoid devitrification. The effects of each cryoprotectant on this mode of heating
      was therefore studied. Gelatin spheres containing vitrifiable concentrations of
      each cryoprotectant were rewarmed from -60 degrees C in a radiofrequency
      applicator. Because the uniformity of heating is related to the dielectric
      properties of the material, these properties were also measured. PD was the most
      suitable. These physical measurements, combined with the measurements of toxicity
      and permeability, indicate that PD is the most favorable cryoprotectant of those
      tested for use in subsequent stages of this study.

PMID- 12061847
TI  - Cryopreservation of vascular endothelial cells as isolated cells and as
      monolayers.
AB  - This paper reports the cryopreservation of an immortalized human endothelial cell
      line (ECV304), either as a single cell suspension or as a confluent layer on
      microcarrier beads. Cell suspensions were exposed to 10% w/w dimethyl sulfoxide
      in a high-potassium solution (CPTes) at 0 degrees C. The cells were then cooled
      to -60 degrees C at controlled rates between 0.3 and 500 degrees C/min and stored
      below -180 degrees C. Samples were thawed in a 37 degrees C water bath and the
      cryoprotectant was removed by serial dilution at 22 degrees C over 6 min. The
      recovery of cell suspensions was assayed by culturing aliquots in 24-well plates
      for 7-9 days and counting the number of colonies that contained >25 cells.
      Maximum survival was 45-50% at cooling rates of 0.3, 1.0, and 10 degrees C/min,
      but decreased to 20% at 50 degrees C/min and to <1% at 500 degrees C/min.
      Biosilon microcarrier beads were used for the attached cells. Confluent beads
      were cryopreserved by exactly the same technique and cell function was assayed by
      measuring active amino acid (leucine) transport at 37 degrees C. Control,
      untreated confluent beads gave approximately 73% of control uptake and negative
      controls (frozen without cryoprotectant) gave approximately 4% uptake. The cells
      attached to beads showed percentage uptakes that were numerically similar to the
      survival of cells in suspension at cooling rates between 10 and 500 degrees
      C/min, but at lower cooling rates the recovery of attached cells increased to 70%
      at 1 degrees C/min and to 85% at 0.3 degrees C/min. These results indicate a
      marked difference in the effect of cooling rate on ECV304 cells depending upon
      attachment.

PMID- 12061848
TI  - Role of elastic fibers in cooling-induced relaxation.
AB  - The objective of this work was to confirm the main role of elastic fibers in
      differing responses of certain vessels during cooling from 37 to 8 degrees C.
      Previous results have shown that the nature of the vessel (conduit vessel vs
      muscular vessel) determines the different behavior (dilatation vs contraction) of
      isolated vessel segments when temperature decreases from 37 to 8 degrees C. In
      this work, it has been demonstrated that vessels with a great amount of elastic
      fibers show a dilatation when cooling. On the other hand, muscular vessels with
      fewer elastic fibers, such as the renal artery, undergo a contraction. The output
      of calcium from intracellular stores causes contraction of the renal artery
      during cooling. In this vessel, vasodilatation occurs only when mechanisms of
      smooth muscle contraction are inactive, as is the case with vessels that have
      undergone a cold storage period of 48 h. The results presented in this work
      confirm that there are two main effects, which directly depend on the vessel
      origin. In conduit arteries, the decrease of temperature induces a vascular
      relaxation, dependent on the elastic component of the vessel wall. In muscular
      vessels, the predominant effect is cooling-induced contraction due to an increase
      of intracellular calcium. This cooling-induced contraction needs the vessel to be
      in optimal conditions with an active metabolism of the muscular cells. These
      results are a crucial issue in the sense of explaining several biomedical
      mechanisms where hypothermia is implicated. The type of vessel implicated in
      procedures, such as isolated organ perfusion, extracorporeal circulation, and
      bypass surgery, must be taken into account.

PMID- 12061849
TI  - Differences among dogs in response of their spermatozoa to cryopreservation using
      various cooling and warming rates.
AB  - Spermatozoa collected from the caudae epididymides of 16 dogs of various breeds
      were suspended in an isotonic salt solution (DIMI medium) containing 0.6 M
      glycerol, frozen in liquid nitrogen, and their "survival" was measured after
      thawing. In the first experimental series, duplicate samples of spermatozoa from
      each of 11 dogs were cooled at rates of 0.5, 3, 11, 58, or 209 degrees C/min,
      stored in liquid nitrogen, and the frozen samples warmed at approximately 830 or
      at 33 degrees C/min. Sperm "survival" was judged by microscopic assessments of
      motility and of membrane integrity, the latter as assayed with Fertilight, a
      double fluorescent stain. Motility of frozen spermatozoa that were thawed
      rapidly, averaged for 11 dogs, was low at low rates, increased to a maximum at 11
      degrees C/min, and then decreased significantly at higher rates (P<0.01). This
      inverted V-shaped curve was also observed with slow thawing, although the
      apparent optimum cooling rate ranged from 3 to 11 degrees C/min. The integrity of
      sperm plasma membranes showed a similar dependence on cooling rate, although the
      percentages of spermatozoa with intact plasma membranes were higher than the
      percentages of motile spermatozoa. Motility of spermatozoa, as a function of
      cooling rate, varied considerably from male to male (P<0.01), whereas membrane
      integrity was much more consistent among the 11 dogs. In the second experimental
      series with spermatozoa from 5 dogs, motility of spermatozoa frozen at 0.5
      degrees C/min and warmed at 3.6, 33, 140, or 830 degrees C/min also exhibited an
      inverted V-shaped survival curve, in this case as a function of warming rate. In
      summary, high survival of frozen-thawed canine epididymal spermatozoa depended on
      both cooling and warming rates, but spermatozoa from each dog exhibited their own
      sensitivity to cooling and warming rates.

PMID- 12061850
TI  - Osmotic sensitivity of canine spermatozoa.
AB  - The objective of this study was to determine osmotic tolerance of canine
      spermatozoa. The study comprised three experiments: (1) spermatozoa suspended
      either in an egg yolk-citrate (EYC) extender or in Kenney skim milk extender were
      exposed to NaCl solutions ranging from 290 to 1500 mOsm; (2) spermatozoa
      suspended in EYC were exposed to 550 to 1500 mOsm solutions of glucose,
      galactose, or fructose; and (3) spermatozoa suspended in EYC or glucose-bovine
      serum albumin (G-BSA) were exposed to 0.6 M (approximately 900 mOsm) or 1.2 M
      (approximately 1600 mOsm) solutions of glycerol, ethylene glycol (EG), or
      dimethyl sulfoxide (Me(2)SO). In all experiments, motility and membrane integrity
      of spermatozoa were assessed after they were diluted into isotonic medium at 37
      degrees C. Exposure of canine spermatozoa to solutions of either NaCl or
      monosaccharides at osmolalities >500 mOsm caused a significant reduction of
      motility (P<0.01). Motility of spermatozoa was more affected by osmotic stress
      than their membrane integrity. Osmotic sensitivity of canine spermatozoa was
      dependent on the type of extender; spermatozoa suspended in the Kenney extender
      were more resistant to osmotic stress than those suspended in the EYC extender.
      Despite their sensitivity to exposure to high concentrations of nonpermeating
      agents, canine spermatozoa were rather resistant to exposure to glycerol and EG.
      However, Me(2)SO was toxic to canine spermatozoa; motility was substantially
      reduced after spermatozoa were exposed to 0.6 M Me(2)SO. The type of extender
      also affected the sensitivity of canine spermatozoa to Me(2)SO; spermatozoa
      suspended in the EYC extender were more resistant than those suspended in G-BSA.
      It was concluded that canine spermatozoa are sensitive to osmotic stress, but are
      tolerant to shrinking and swelling caused by exposure to permeating
      cryoprotectants.

PMID- 12061851
TI  - Recent Insights into the pathogenesis of pre-eclampsia.
AB  - Pre-eclampsia is more than pregnancy induced hypertension. The emerging view
      described in this presentation is that pre-eclampsia is secondary to the
      interactions of reduced placental perfusion with diverse maternal factors that
      alter endothelial function. The maternal contribution is from factors that
      antedate pregnancy and are influenced by the usual metabolic adaptations of
      pregnancy. The endothelium and other targets for the effects of these
      interactions are more sensitive to insults during pregnancy because of activation
      of the inflammatory cascade as a normal part of pregnancy. At least part of the
      response to reduced placental perfusion may be a fetal adaptive response to
      attempt to overcome the reduced delivery of nutrients. A reasonable convergence
      point for the interaction is at the level of oxidative stress. This hypothesis
      has both encouraging and discouraging corollaries. The diversity of maternal
      factors argues that there will be no single gene to explain the disorder and no
      single 'magic bullet' to treat the disorder. However, it is encouraging that the
      recognition of maternal predisposition to the disorder directs therapy to prevent
      pre-eclampsia at a specific target in subsets of women. Finally, the suggestion
      that some of the maternal alterations are due to fetal adaptive responses
      encourages careful choices of agents and meticulous infant follow up in well
      planned clinical trials.

PMID- 12061853
TI  - Altered plasma concentrations of leptin, transforming growth factor-beta(1) and
      plasminogen activator inhibitor type 2 at 18 weeks of gestation in women destined
      to develop pre-eclampsia. Circulating markers of disturbed placentation?
AB  - BACKGROUND: In many pre-eclamptic women the placentation process seems to be
      disturbed. Our objective was to investigate if disturbed placentation in pre
      eclamptic women may be recognized in early second trimester as altered plasma
      levels of factors involved in the formation of the uteroplacental unit. METHODS:
      In a prospective study of 2190 pregnant women we compared plasma leptin,
      transforming growth factor-beta(1) (TGF-beta(1)) and plasminogen activator
      inhibitor type 2 (PAI-2) concentrations at 18 weeks' gestation in 71 women with
      subsequent pre-eclampsia and 71 controls matched for age, parity and first
      trimester body mass index. RESULTS: Leptin and TGF-beta(1) concentrations were
      lower and PAI-2 concentration higher in women destined to develop pre-eclampsia
      relative to controls (leptin: median (25-75 percentiles): 19.0 (14.5-29.0) vs
      25.0 (16.0-35.0) ng/ml (p =0.03), TGF-beta(1): 3.2 (2.0-6.1) vs 5.3 (3.8-7.1)
      ng/ml (P=0.01) and PAI-2: 78.8 (65.1-118.1) vs 67.6 (61.6-79.6) ng/ml (P=0.002)).
      OR (95 per cent CI) for pre-eclampsia for women in the upper quartile compared to
      women in the lower quartile were: leptin: 0.2 (0.03-0.7), TGF-beta(1): 0.2 (0.08
      0.7) and PAI-2: 3.1 (1.2-8.2). CONCLUSIONS: Altered plasma concentrations levels
      of factors involved in the process of placentation in women destined to develop
      pre-eclampsia, indicate that disturbed formation of the uteroplacental unit is
      reflected in the maternal circulation before 20 weeks' gestation.

PMID- 12061852
TI  - Localization of indoleamine 2,3-dioxygenase and 4-hydroxynonenal in normal and
      pre-eclamptic placentae.
AB  - This study was undertaken to compare placental levels of 2,3-Dioxygenase (IDO), a
      free radical scavenger, and 4-Hydroxynonenal (4-HNE), a major by-product of lipid
      peroxidation, in normal and pre-eclamptic pregnancies. Placentae were collected
      at caesarean section from women with a term, normal singleton pregnancy (37-40
      weeks' gestation, n=10) and women with a term singleton pregnancy complicated by
      pre-eclampsia (n=10). IDO and 4-HNE localization and intensity was studied by
      semi-quantitative immunohistochemistry and differences between groups were
      analysed using the Mann-Whitney U test. Immunostaining for IDO was located
      primarily in endothelial cell nuclei, with a reduced level of staining in the
      cytoplasm, in most capillaries from all placentae examined. A significantly
      higher level of IDO immunostaining was observed in normal placentae compared to
      pre-eclamptic placentae (P=0.008). 4-HNE was located mainly in the cytoplasm of
      syncytiotrophoblast cells of all placentae examined. There were no significant
      differences in the pattern or intensity of 4-HNE immunostaining levels between
      normal and pre-eclamptic pregnancies (P=0.684). Our IDO results support the
      hypothesis of decreased anti-oxidative capability in the placenta and the
      possibility of an ineffective compensatory mechanism against increased oxidative
      stress in the fetus.

PMID- 12061855
TI  - Glucose transport and system A activity in syncytiotrophoblast microvillous and
      basal plasma membranes in intrauterine growth restriction.
AB  - The mechanisms underlying the reduced fetal plasma concentrations of amino acids
      and glucose associated with intrauterine growth restriction (IUGR) remain to be
      fully established. The activity of the amino acid transporter system A has been
      shown to be reduced in the syncytiotrophoblast microvillous membrane (MVM) in
      IUGR, however the impact of these changes on transplacental transport is
      difficult to assess without information on system A activity in the basal plasma
      membrane (BM). In this study we measured system A activity and mediated D-glucose
      uptake using radiolabelled substrates and rapid filtration techniques, and
      glucose transporter isoform 1 (GLUT 1) protein expression using Western blots in
      MVM and BM isolated from human placentas. In term IUGR (n=11) MVM system A
      activity was unaltered compared to controls (n=9). In contrast, system A activity
      in MVM was reduced by 50 per cent (P< 0.05) in preterm IUGR (n=8, gestational age
      28-36 weeks) as compared to controls (n=8, gestational age 28-35 weeks). BM
      system A activity was unaltered in both IUGR groups. Similarly, MVM and BM GLUT 1
      expression and mediated D-glucose uptake was not affected by IUGR. In all preterm
      IUGR pregnancies signs of severe fetal compromise were present whereas term IUGR
      fetuses were less affected. These data support the view that MVM system A
      activity is related to the severity of compromise in IUGR. The markedly reduced
      system A activity in MVM in preterm IUGR together with the unaltered activity in
      BM is consistent with a decreased transplacental transport of neutral amino acids
      in this pregnancy complication. The hypoglycemia present in utero in some IUGR
      fetuses is not caused by a decreased glucose transport capacity across the
      syncytiotrophoblast plasma membranes.

PMID- 12061854
TI  - Na(+)/K(+)-ATPase activity and expression in syncytiotrophoblast plasma membranes
      in pregnancies complicated by diabetes.
AB  - Many of the transport processes across the syncytiotrophoblast (ST), such as
      amino acid transport, are Na(+)-coupled. The maintenance of a low intracellular
      Na(+) concentration by Na(+)/K(+)-ATPase is therefore crucial for placental
      transport of nutrients and consequently, foetal growth. In pregnancies
      complicated by diabetes foetal growth is often accelerated despite rigorous
      glycemic control of the mother, however the underlying mechanisms are not fully
      understood. We tested the hypothesis that Na(+)/K(+)-ATPase in ST plasma
      membranes is up-regulated in diabetic pregnancies associated with accelerated
      growth. ST microvillous (MVM) and basal (BM) plasma membranes were purified from
      term placentas of normal pregnancies (control, n=13) and pregnancies complicated
      by insulin-dependent diabetes mellitus (n=7) or gestational diabetes (n=6). All
      mothers with diabetes gave birth to large for gestational age babies. The
      Na(+)/K(+)-ATPase alpha(1)-subunit protein expression (Western blot) in MVM and
      BM was unaltered by diabetes. Na(+)/K(+)-ATPase activity (K(+)-stimulated,
      ouabain-sensitive phosphatase activity) in ST plasma membranes was not affected
      by diabetes. This is the first study of Na(+)/K(+)-ATPase in ST membranes of the
      human placenta in diabetes. Our data show that accelerated foetal growth in
      diabetic pregnancies is not associated with elevated ST Na(+)/K(+)-ATPase protein
      expression or activity.

PMID- 12061856
TI  - Characterization of small arteries isolated from the human placental chorionic
      plate.
AB  - Despite the essential role of the placenta in pregnancy, the control of the blood
      flow within the fetoplacental circulation is poorly understood. A handful of
      myography studies have directly assessed the role of vasoactive agonists in
      fetoplacental vasculature contractility but have used a range of steady-state
      conditions. Our aim, therefore, was to determine the optimal vessel diameter and
      oxygen tension to assess vascular function in small arteries isolated from the
      chorionic plate of normal term placentae. Biopsies were obtained from term
      placentae from uncomplicated pregnancies. Small arteries were dissected from the
      chorionic plate, mounted onto a wire myograph in HCO3(-) -buffered physiological
      salt solution at 37 degrees C and equilibrated for 20 min. Two methods for
      normalization of the optimal length/diameter for contractility of chorionic plate
      small arteries were assessed. Both classical normalization (CN) and length
      tension curve (LTC) methods produced similar data. These data were agonist
      independent. Data for CN and LTC were unaffected but maximal force generation
      (for U46619) was decreased in reduced oxygen tensions. Using conditions for
      optimal tension production in chorionic plate small arteries the thromboxane
      mimetic U46619 produced the greatest and most reproducible constrictive effect.
      Relaxations were only achieved with endothelial-independent agonists (sodium
      nitroprusside and papaverine).

PMID- 12061858
TI  - Placentation in the capybara (Hydrochaerus hydrochaeris), Agouti (Dasyprocta
      aguti) and paca (Agouti paca).
AB  - Placentae of three hystricimorph rodents--capybara, agouti and paca--were
      examined by conventional histology, immunohistochemistry for cytokeratin and
      vimentin, and TUNEL staining. The placentae were divided into lobules of
      labyrinthine syncytium separated by interlobular and marginal trophoblast. The
      subplacenta comprised cytotrophoblasts, supported on lamellae of allantoic
      mesoderm, and syncytiotrophoblast. The central excavation was still apparent in
      the definitive placenta of capybara. In agouti and paca, the decidua of the
      junctional zone formed a mesoplacenta comprising a capsule and a pedicle. Towards
      term the pedicle formed a tenuous attachment between placenta and uterine wall
      comprising a few maternal vessels surrounded by degraded tissue. In paca
      placenta, it was shown by TUNEL staining that breakdown of this tissue occurred
      by apoptosis. The visceral yolk sac was highly villous and, in agouti, the yolk
      sac villi were extremely long. Lateral to its attachment to the placenta, the
      fetal surface was covered with non-vascular yolk sac endoderm. A layer of
      spongiotrophoblast cells was interposed between the endoderm and the marginal
      trophoblast.

PMID- 12061857
TI  - Adeno-associated virus DNA in human gestational trophoblastic disease.
AB  - Previous studies had shown a correlation between infection with the human adeno
      associated virus (AAV) and spontaneous abortion in early pregnancy. Furthermore,
      AAV DNA had been detected in cells of the human trophoblast lines, Jeg-3, JAr,
      and BeWo, in cells of the human amnion line, FL, and in trophoblasts from amnion
      fluids. Infectious AAV virions could be isolated from amnion fluids. To further
      analyse AAV infection during pregnancy, we tested material from Gestational
      Trophoblastic Disease for the presence of AAV DNA. With 63 tissue samples from
      patients from Brazil, including 49 hydatiform moles and 14 choriocarcinomas,
      nested PCR was performed to detect the presence of AAV DNA. In addition, 15
      samples from spontaneous abortions were analysed. AAV DNA was found in 43 samples
      (28/49 hydatiform moles, 4/14 choriocarcinomas, 11/15 miscarriage material).
      These findings confirm AAV infection of embryo-derived tissue in humans and
      further suggest a role of AAV in miscarriage and trophoblastic disease.

PMID- 12061859
TI  - Bovine retained placenta: hormonal concentrations in fetal and maternal placenta.
AB  - The aim of this study was to evaluate the relationship between the occurrence of
      retention of the fetal membranes (RFM) and the hormonal concentrations of
      progesterone, estradiol-17beta, prostaglandin E(2) (PGE(2)), prostaglandin
      F(2alpha) (PGF(2alpha)), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1
      and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was
      induced in nine Holstein cows by a single injection of PGF(2alpha) on Day 274 of
      gestation. Six out of nine cows in the induced group did not release the fetal
      membranes within 12 h after parturition and served as the RFM group, and the
      remaining three cows in that group, which released their fetal membranes within
      12 h, served as the non-RFM group. Five other cows calved spontaneously and
      served as controls. The placental tissues were collected immediately (0 h) and at
      6 h after parturition. The hormonal concentrations were measured by enzyme
      immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control
      cows. There were no differences in P4 and E2 concentrations among the RFM, non
      RFM and control groups. The mean PGF(2alpha) concentration of the RFM group was
      lower than those of the non-RFM and control groups in the maternal part of the
      placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group
      were lower than those at 0 and 6 h after parturition in the non-RFM group.
      Additionally, the Ang II concentration of the RFM group in both the maternal and
      fetal parts of placental tissues tended to be higher than those of the other
      groups. In conclusion, the present results suggest that ET-1 and Ang II may play
      differential tissue-specific roles in the placental unit that may amplify the
      local endocrinological cascade involving OT, OT-R and PGF(2alpha) interactions
      which are necessary for normal placental separation in the cow.

PMID- 12061860
TI  - Transplacental lactate dehydrogenase-elevating virus (LDV) transmission: immune
      inhibition of umbilical cord infection, and correlation of fetal virus
      susceptibility with development of F4/80 antigen expression.
AB  - Maternal-to-fetal transmission of the murine lactate dehydrogenase-elevating
      virus (LDV) has been previously shown to be regulated by maternal immunity as
      well as gestational age. For the present study, the role of maternal immunity in
      placental and umbilical cord virus protection was studied, and virus targeting of
      umbilical cord and fetal macrophages was correlated with expression of the F4/80
      macrophage phenotypic marker. The results showed that LDV-infected macrophages
      appeared in umbilical cord by 24 h post-infection of pregnant mice, and some LDV
      infected macrophages displayed the F4/80 phenotype. This potential reservoir of
      virus for the fetus was inhibited by passive immunization of pregnant mice with
      IgG anti-LDV antibodies, which rapidly concentrated in the placenta and umbilical
      cord. Probing of umbilical cord cells with antibodies directed at MHC genetic
      markers demonstrated the presence of both maternal and fetal cells in umbilical
      cords. A strong developmental correlation was observed between fetal F4/80
      expression and LDV susceptibility, at about 13.6 days of gestation. These results
      demonstrate immune suppression of free and cell-associated virus in umbilical
      cord, thus defining a potentially important mechanism for immune protection of
      the fetus from transplacental virus infection. The results also clarify the
      developmental basis for fetal susceptibility to LDV infection.

PMID- 12061861
TI  - Evidence for fatty acid oxidation in human placenta, and the relationship of
      fatty acid oxidation enzyme activities with gestational age.
AB  - Fetal disorders of mitochondrial fatty acid oxidation have recently been
      associated with obstetric complications including pre-eclampsia, Hemolysis,
      Elevated Liver enzymes, Low Platelets (HELLP) syndrome, placental floor infarct,
      and Acute Fatty Liver of Pregnancy (AFLP). These diseases occur in about a third
      of the mothers who are heterozygous for a defect in long chain 3-hydroxyacyl-CoA
      dehydrogenase (LCHAD) enzyme and who bear a fetus homozygous for the defect. The
      mechanism of this association is not clearly understood. In this study, we
      provide evidence that the placenta may be the site of production of toxic
      intermediates of fatty acid metabolism, which accumulate to cause liver damage in
      the mother. We show that two critical enzymes of long chain fatty acid
      metabolism, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and short chain 3
      hydroxyacyl-CoA dehydrogenase (SCHAD), are active in the normal human placenta.
      There is an inverse correlation between the enzyme activity of both the enzymes
      and maternal gestational age during the second and third trimesters. We believe
      that the demonstration of fatty acid oxidation enzyme activity by the placenta is
      the first step towards assessing a possible role for fetal/placental fatty acid
      oxidation defects in the pathogenesis of a subset of pregnancy complications.

PMID- 12061862
TI  - Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the
      nigrostriatal pathway.
AB  - Human idiopathic Parkinson's disease (PD) is a progressive neurodegenerative
      disorder that is primarily characterized by degeneration of the dopaminergic
      neurons of the nigrostriatal pathway. Different 6-OHDA rat models of PD have been
      developed in which this toxin has been injected into different parts of the
      nigrostriatal pathway: (a) the medial forebrain bundle which leads to extensive
      dopamine (DA) depletion; (b) the substantia nigra pars compacta, which leads to
      more specific and moderate DA depletions; and (c) subregions of the caudate
      putamen complex (CPu), which also leads to specific DA depletions. In this
      article we review the dopaminergic depletion and behavioral consequences of 6
      OHDA lesions in the rat. It was examined whether the relation between DA
      depletion and behavioral deficits mimic idiopathic PD. In addition, it was
      evaluated which model most closely approximates the human situation, especially
      in relation to the stage of this progressive disease. It was concluded that with
      respect to the site of the lesion, rats with partial lesions of the ventrolateral
      CPu are the most appropriate models to study early and late stages of PD. The
      choice of the behavioral parameters determines the use of unilateral or bilateral
      lesions, although it is obvious that the bilateral model mimics the human
      situation more closely.

PMID- 12061864
TI  - Reactive astrocytes express bis, a bcl-2-binding protein, after transient
      forebrain ischemia.
AB  - Bis (also called Bag-3), identified as a novel Bcl-2-interacting protein, has
      been shown to enhance anti-cell death activity of Bcl-2. Because
      ischemia/reperfusion induces expression of Bcl-2, we examined the changes in the
      pattern of Bis expression in the adult rat hippocampus after transient forebrain
      ischemia. Western blot analysis with protein extracts from the hippocampus showed
      that, compared with controls, levels of Bis were markedly increased seven days
      after ischemia. An immunohistochemical study showed that the expression of Bis
      increased preferentially in the CA1 and the dentate hilar regions, and peaked at
      3-7 days after reperfusion. The temporal and spatial patterns of expression for
      both Bis and glial fibrillary acidic protein (GFAP) were very similar, and double
      immunofluorescence histochemistry showed that Bis was expressed in reactive
      astrocytes, which express GFAP. Immunolabeling of adjacent sections with anti-Bcl
      2 and anti-Hsp70 antibodies revealed that the pattern of Bis expression closely
      correlates with that of Bcl-2, but clearly differs from that of Hsp70.
      Coexpression of Bis and Bcl-2 in reactive astrocytes was confirmed by double
      immunofluorescence histochemistry. Our results demonstrate that reactive
      astrocytes transiently up-regulate Bis after ischemia/reperfusion in the adult
      rat hippocampus. However, the precise role of Bis in the astrocytic response to
      ischemia/reperfusion in relation to Bcl-2 remains to be determined.

PMID- 12061863
TI  - AF5, a CNS cell line immortalized with an N-terminal fragment of SV40 large T:
      growth, differentiation, genetic stability, and gene expression.
AB  - Central nervous system progenitor cells that are self-renewing in culture and
      also differentiate under controlled conditions are potentially useful for
      developmental studies and for cell-based therapies. We characterized growth and
      plasticity properties and gene expression in a rat mesencephalic cell line, AF5,
      that was immortalized with an N-terminal fragment of SV40 large T (T155g). For
      over 150 population doublings in culture, the growth rate of AF5 cells remained
      steady, the cells remained responsive to bFGF, and telomerase activity and
      telomere lengths were unchanged. While karyotype analyses revealed some
      chromosomal abnormalities, these were also unchanged over time; additionally, no
      mutations in p53 gene sequences were found, and wild-type p53 activation was
      normal. AF5 cells produced PDGF, TGFbeta1, TGFbeta2, and bFGF. Similar to primary
      progenitor cells, AF5 cells retained their plasticity in culture; they could be
      propagated in an undifferentiated state as "neurospheres" in serum-free media or
      as adherent cultures in serum-containing media, and they differentiated when
      allowed to become confluent. Adherent subconfluent actively growing cultures
      expressed a marker for immature neurons, nestin, while few cells expressed the
      mature neuronal cell marker betaIII-tubulin. Confluent cultures ceased growing,
      developed differentiated morphologies, contained few or no nestin-expressing
      cells, and acquired betaIII-tubulin expression. Global gene expression was
      examined using a 15,000 gene microarray, comparing exponential growth with and
      without bFGF stimulation, and the differentiated state. The AF5 cell line
      exhibited stable genetic and growth properties over extended periods of time,
      while retaining the ability to differentiate in vitro. These data suggest that
      the AF5 cell line may be useful as an in vitro model system for studies of neural
      differentiation.

PMID- 12061866
TI  - In vivo assessment of lipid peroxidation products associated with age-related
      neurodegenerative diseases.
AB  - Numerous in vitro and cell culture experiments indicate that oxidative damage
      decreases astrocyte glutamate transport activity, and it has been proposed that
      products of lipid peroxidation, particularly 4-hydroxy-2-nonenal, may contribute
      to neurodegenerative diseases via inhibition of glutamate or glucose transporter
      activity. We have directly tested the hypothesis that lipid peroxidation products
      impair glutamate and glucose transport in vivo. Lipid peroxidation products that
      irreversibly modify protein lysyl residues caused a two- to sixfold elevation in
      extracellular glutamate in striatum and cerebral cortex of both freely moving and
      anesthetized rats undergoing microdialysis. No concomitant change in
      extracellular glucose concentrations was observed. Furthermore, lipid
      peroxidation product-evoked extracellular glutamate appeared to be derived from
      nonneuronal sources. Our results demonstrate a biochemical mechanism whereby
      oxidative damage products can increase extracellular glutamate levels in vivo,
      providing support for the proposal that oxidative damage leads to inhibition of
      glutamate transport and thereby may contribute to the progression of
      neurodegenerative diseases.

PMID- 12061865
TI  - Changes in serotonin, serotonin transporter expression and serotonin denervation
      supersensitivity: involvement in chronic central pain after spinal hemisection in
      the rat.
AB  - Spinal cord injury (SCI) results in abnormal locomotor and pain syndromes in
      humans. In a rodent SCI model, T13 unilateral spinal hemisection results in
      bilateral mechanical allodynia and thermal hyperalgesia, partly by interruption
      of tonic descending serotonin (5-HT) inhibition. In the current study, we
      examined changes in density and distribution of 5-HT and 5-HT(T) in cervical (C8)
      and lumbar (L5) enlargements after T13 spinal hemisection and studied the effects
      of intrathecally delivered 5-HT (10, 21, and 63 microg), 5-HT antagonist
      methysergide (125 microg/kg), and 5-HT reuptake inhibitor fluvoxamine (75
      microg/kg) on pain-related behaviors. Thirty-day-old male Sprague-Dawley rats
      were spinally hemisected and sacrificed at 3 (n = 20) and 28 (n = 20) days
      postsurgery for immunohistochemistry, Western blot, and ELISA analysis and
      compared against sham-operated animals (n = 10). At day 3, C8 5-HT levels were
      not significantly changed but at L5 there was a significant decrease in
      ipsilateral 5-HT in laminae I-II followed by incomplete recovery at 28 days
      postinjury. At both 3 and 28 days postinjury, C8 5-HT(T) levels were not
      significantly changed, but at L5 there was significant ipsilateral up-regulation
      of 5-HT(T) in laminae I-II. A second group of animals (n = 30) was hemisected
      and, starting at 28 days postinjury, behaviorally tested with intrathecal
      compounds. Increasing doses of 5-HT attenuated both fore- and hindlimb mechanical
      allodynia and thermal hyperalgesia, and effects of endogenous 5-HT were
      attenuated by methysergide and enhanced with fluvoxamine, all without locomotor
      alterations. Sham controls (n = 10) were unaffected. Thus, permanent changes
      occur in 5-HT and 5-HT(T) after SCI, denervation 5-HT supersensitivity develops,
      and modulation of 5-HT attenuates pain-related behaviors. Insight gained by these
      studies may aid in the understanding of dynamic 5-HT systems which will be useful
      in treating chronic central pain after SCI.

PMID- 12061867
TI  - Differentiation of the RN33B cell line into forebrain projection neurons after
      transplantation into the neonatal rat brain.
AB  - The rat neural cell line RN33B has a remarkable ability to undergo region
      specific neuronal differentiation after transplantation into the CNS. To further
      study its neurogenic properties in vivo, we used a recombinant lentiviral vector
      to genetically label the cells with the Green Fluorescent Protein (GFP) gene
      before implantation into the striatum/cortex, hippocampus, or mesencephalon of
      newborn rats. Three weeks after implantation, about 1-2% of the GFP-expressing
      cells had developed morphologies typical of neurons, astrocytes, or
      oligodendrocytes, the rest remained as either immature or undifferentiated nestin
      positive cells. At 15-17 weeks postgrafting, the immature cells had disappeared
      in most graft recipients and only cells with neuronal or glial morphologies
      remained in similar numbers as at 3 weeks. The GFP distributed throughout the
      expressing cells, revealing fine morphological details, including dendrites with
      spines and extensive axonal projections. In all forebrain regions, the grafted
      cells differentiated into neurons with morphologies characteristic for each site,
      including large numbers of pyramidal-like cells in the cortex and the
      hippocampus, giving rise to dense projections to normal cortical target regions
      and to the contralateral hippocampus, respectively. In lower numbers, it was also
      possible to identify GFP-positive granulelike cells in the hippocampus, as well
      as densely spiny neurons in the striatum. In the mesencephalon by contrast, cells
      with astrocytic features predominated. The ability of the grafted RN33B cells to
      undergo region-specific differentiation into highly specialized types of
      forebrain projection neurons and establish connections with appropriate targets
      suggests that cues present in the microenvironment of the neonatal rat brain can
      effectively guide the development of immature progenitors, also in the absence of
      ongoing neurogenesis.

PMID- 12061868
TI  - Dopamine D1 receptor changes due to caesarean section birth: effects of
      anesthesia, developmental time course, and functional consequences.
AB  - There is an epidemiological association between increased obstetric complications
      and disorders involving CNS dopamine dysregulation, such as schizophrenia. In
      light of this, a rat model of global hypoxia during Caesarean section (C-section)
      birth has been used to directly test if birth complications can produce long-term
      dopaminergic dysregulation. Previous studies have shown that, compared to vaginal
      birth, C-section birth alone (without additional global hypoxia) is sufficient to
      increase D1-like receptor binding in rat brain at adulthood. The current study
      examined (1) the developmental time course of changes in D1-like or D2-like
      receptors following C-section birth; (2) whether C-section birth from isoflurane
      anesthetized dams also results in altered D1-like receptor levels, as does C
      section from decapitated dams; and (3) behavioral responses to D1 and D2 agonists
      in rats born vaginally compared to C-section. Increases in nucleus accumbens D1
      like receptor binding due to C-section birth were observed only at adulthood (3
      months) but not prepubertally (1 month or 2 weeks). D2-like receptor binding
      levels were unaffected by C-section birth across the three developmental time
      points. Compared to vaginal birth, D1-like receptors were increased following C
      section birth from isoflurane-anesthetized dams, as well as from decapitated
      dams. Adult rats that had been born by C-section showed enhanced D1 potentiation
      of D2-induced locomotor behavior. These studies indicate that C-section birth,
      from either anesthetized or unanesthetized dams, results in postpubertal
      increases in D1-like receptor binding and enhanced functional responses to D1
      receptor activation.

PMID- 12061869
TI  - Object recognition memory and cholinergic parameters in mice expressing human
      presenilin 1 transgenes.
AB  - Most autosomal dominant forms of Alzheimer disease (AD) are related to missense
      mutations in the human presenilin (PS) 1 gene. Although the underlying mechanisms
      associated with pathophysiology of AD have yet to be clearly established,
      pathogenic mutations in the PS1 gene influence the processing of beta-amyloid
      precursor protein, leading to increased production and deposition of highly
      fibrillogenic amyloid beta(1-42) peptide in the brains of AD patients. As
      cognitive dysfunction in AD is associated with a dramatic loss of cholinergic
      innervation particularly in the hippocampus and neocortex, we investigated
      learning and cholinergic neurochemistry in transgenic mice expressing pathogenic
      mutant L286V or wild-type(wt) human PS1 transgenes. Relative to wt, the L286V PS1
      transgenic mice exhibited reduced sensorimotor activity and marked deterioration
      of object memory between 3 and 5 h after the first encounter. Activity of the
      biosynthetic enzyme choline acetyltransferase was not altered in the hippocampus,
      frontoparietal cortex, or striatum of mutant transgenic mice relative to wt
      transgenic or littermate nontransgenic controls. No differences in the densities
      of M1/[3H]pirenzepine, M2/[3H]AF-DX 384, or alpha(7) nicotinic/125I-alpha
      bungarotoxin receptor binding sites were evident in any brain regions among L286V
      PS1 transgenic, wt PS1 transgenic, and littermate nontransgenic controls. These
      results suggest that overexpression of a mutated PS1 gene induces a subtle
      alteration in object memory without affecting cholinergic neurochemistry.

PMID- 12061870
TI  - Phosphatidylinositol-3-kinase-Akt kinase and p42/p44 mitogen-activated protein
      kinases mediate neurotrophic and excitoprotective actions of a secreted form of
      amyloid precursor protein.
AB  - The alpha-secretase-derived form of the amyloid precursor protein (sAPPalpha),
      which is released from neurons in an activity-dependent manner, has been shown to
      promote long-term survival of hippocampal and cortical neurons in culture and can
      protect those neurons against excitotoxic and ischemic injury in culture and in
      vivo. The signal transduction pathway(s) activated by sAPPalpha has not been
      established. We now report that sAPPalpha activates the phosphatidylinositol-3
      kinase (PI(3)K)-Akt kinase signaling pathway in cultured hippocampal neurons.
      sAPPalpha also stimulates phosphorylation of p42 (ERK1) and p44 (ERK2) mitogen
      activated protein (MAP) kinases by a PI(3)K-independent pathway. Treatment of
      neurons with sAPPalpha protects them against death induced by trophic factor
      deprivation and exposure to glutamate, and these survival-promoting effects of
      sAPPalpha are abolished or attenuated when either PI(3)K or p42/p44 MAP kinases
      are selectively blocked. Exposure of neurons to sAPPalpha resulted in a decrease
      in the level of IkappaBbeta and an increase in NF-kappaB DNA binding activity,
      both of which were blocked by wortmannin, suggesting that the transcription
      factor NF-kappaB may be a downstream target of the PI(3)K-Akt pathway that may
      play a role in the cell survival-promoting action of sAPPalpha. These findings
      suggest that the PI(3)K-Akt pathway and p42/p44 MAP kinases mediate responses of
      neurons to sAPPalpha in physiological and pathological settings, with
      implications for synaptic plasticity and the pathogenesis of Alzheimer's disease.

PMID- 12061871
TI  - Structural differences of matrix metalloproteinases with potential implications
      for inhibitor selectivity examined by the GRID/CPCA approach.
AB  - The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which
      have been the focus of a lot of research in recent years because of their
      involvement in various disease conditions. In this study, structures of 10
      enzymes (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP14, and MMP20) were
      examined with the intention of highlighting regions that could be potential sites
      for obtaining selectivity. For this purpose, the GRID/CPCA approach as
      implemented in GOLPE was used. Counterions were included to take into account the
      different electrostatic properties of the proteins, and the GRID calculations
      were performed, allowing the protein side chains to move in response to
      interaction with the probes. In the search for selectivity, the MMPs are known to
      be a very difficult case because the enzymes of this family are very similar. The
      well-known differences in the S1' pocket were observed, but in addition, the
      pockets S3 and S2 called for attention. This is an observation that emphasizes
      the need for design of inhibitors exploiting the unprimed side of the active
      site, if possible, in combination with the S1' site. Despite small differences, a
      rational usage of the findings described in this work should make it possible to
      use a combination of the features of the individual enzyme pockets, making most
      of the MMP enzymes possible targets for selective inhibition. The results suggest
      the possibility of distinguishing between 8 of the 10 enzymes by this approach.

PMID- 12061872
TI  - Suitability of molecular descriptors for database mining. A comparative analysis.
AB  - Database mining methods rely on the molecular descriptors used to characterize a
      structural database. In the present investigation, five different types of
      descriptors (log P, UNITY fingerprints, ISIS keys, VolSurf, and GRIND) are
      applied to characterize various databases (n = 1007, 100, and 229) comprising
      drugs almost exclusively. The validity of the descriptors is comparatively
      analyzed via principal component analysis and its hierarchical variant, consensus
      principal component analysis. Both pharmacodynamic and pharmacokinetic aspects of
      database mining are treated. For pharmacodynamic aspects, clustering behavior
      achieved with the different descriptors is tested on the chemically homogeneous
      beta-blockers, benzodiazepines, and penicillins and on the chemically more
      diverse class I antiarrhythmics. The following ranking is observed: UNITY
      fingerprints > ISIS keys and GRIND > VolSurf > log P. Regarding information
      content, the CPCA superweight plot indicates similarity between fingerprints and
      ISIS keys as well as between VolSurf and log P, while GRIND differs from all the
      remaining descriptors. Solubility data and blood/brain barrier penetrating
      behavior serve as test cases for pharmacokinetic aspects. Comparison of the
      descriptors applied to these data reveals that VolSurf has the most realistic and
      consistent behavior, GRIND shows intermediate behavior, while UNITY fingerprints
      and ISIS keys are not well suited for pharmacokinetic profiling. From this
      comparative analysis, we conclude that VolSurf descriptors exhibit particular
      advantages in treating pharmacokinetic aspects; UNITY fingerprints, ISIS keys,
      and GRIND descriptors are of special value for tackling pharmacodynamic aspects
      of database mining. The parameter log P is of limited applicability in database
      mining because of rather poor reliability and lack of completeness of data.

PMID- 12061873
TI  - Synthesis and structure-activity relationship study of potent trypanocidal thio
      semicarbazone inhibitors of the trypanosomal cysteine protease cruzain.
AB  - American trypanosomiasis, or Chagas' disease, is the leading cause of heart
      disease in Latin America. Currently there is an urgent need to develop
      antitrypanosomal therapy due to the toxicity of existing agents and emerging drug
      resistance. A novel series of potent thio semicarbazone small-molecule inhibitors
      of the Trypanosoma cruzi cysteine protease cruzain have been identified. Some of
      these inhibitors have been shown to be trypanocidal. We initially discovered that
      3'-bromopropiophenone thio semicarbazone (1i) inhibited cruzain and could cure
      mammalian cell cultures infected with T. cruzi. 3'-Bromopropiophenone thio
      semicarbazone showed no toxicity for mammalian cells at concentrations that were
      trypanocidal. Following this lead, more than 100 compounds were designed and
      synthesized. A specific structure-activity relationship (SAR) was established,
      and many potent analogues with IC(50) values in the low nanomolar range were
      identified. Eight additional analogues were trypanocidal in a cell culture assay,
      and this indicates that aryl thio semicarbazone is a productive scaffold for
      killing the parasites. Kinetic studies show that these are time-dependent
      inhibitors. Molecular modeling studies of the enzyme-inhibitor complex have led
      to a proposed mechanism of interaction as well as insight into the SAR of the
      thio semicarbazone series. The nonpeptide nature of this series, small size, and
      extremely low cost of production suggest this is a promising direction for the
      development of new antitrypanosome chemotherapy.

PMID- 12061874
TI  - Synthesis and structure-activity relationships of amide and hydrazide analogues
      of the cannabinoid CB(1) receptor antagonist N-(piperidinyl)- 5-(4-chlorophenyl)
      1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716).
AB  - Analogues of the biaryl pyrazole N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4
      dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716; 5) were synthesized
      to investigate the structure-activity relationship (SAR) of the aminopiperidine
      region. The structural modifications include the substitution of alkyl
      hydrazines, amines, and hydroxyalkylamines of varying lengths for the
      aminopiperidinyl moiety. Proximity and steric requirements at the aminopiperidine
      region were probed by the synthesis of analogues that substitute alkyl hydrazines
      of increasing chain length and branching. The corresponding amide analogues were
      compared to the hydrazides to determine the effect of the second nitrogen on
      receptor binding affinity. The N-cyclohexyl amide 14 represents a direct methine
      for nitrogen substitution for 5, reducing the potential for heteroatom
      interaction, while the morpholino analogue 15 adds the potential for an
      additional heteroatom interaction. The series of hydroxyalkyl amides of
      increasing chain length was synthesized to investigate the existence of
      additional receptor hydrogen binding sites. In displacement assays using the
      cannabinoid agonist [(3)H](1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4
      (3-hydroxypropyl) cyclohexan-1-ol (CP 55 940; 2) or the antagonist [(3)H]5, 14
      exhibited the highest CB(1) affinity. In general, increasing the length and bulk
      of the substituent was associated with increased receptor affinity and efficacy
      (as measured in a guanosine 5'-triphosphate-gamma-[(35)S] assay). However, in
      most instances, receptor affinity and efficacy increases were no longer observed
      after a certain chain length was reached. A quantitative SAR study was carried
      out to characterize the pharmacophoric requirements of the aminopiperidine
      region. This model indicates that ligands that exceed 3 A in length would have
      reduced potency and affinity with respect to 5 and that substituents with a
      positive charge density in the aminopiperidine region would be predicted to
      possess increased pharmacological activity.

PMID- 12061875
TI  - Antifungal agents. 10. New derivatives of 1-[(aryl)[4-aryl-1H-pyrrol-3-yl]methyl]
      1H-imidazole, synthesis, anti-candida activity, and quantitative structure
      analysis relationship studies.
AB  - The synthesis, anti-Candida activity, and quantitative structure-activity
      relationship (QSAR) studies of a series of 2,4-dichlorobenzylimidazole
      derivatives having a phenylpyrrole moiety (related to the antibiotic
      pyrrolnitrin) in the alpha-position are reported. A number of substituents on the
      phenyl ring, ranging from hydrophobic (tert-butyl, phenyl, or 1-pyrrolyl moiety)
      to basic (NH(2)), polar (CF(3), CN, SCH(3), NO(2)), or hydrogen bond donors and
      acceptor (OH) groups, were chosen to better understand the interaction of these
      compounds with cytochrome P450 14-alpha-lanosterol demethylase (P450(14DM)).
      Finally, the triazole counterpart of one of the imidazole compounds was
      synthesized and tested to investigate influence of the heterocyclic ring on
      biological activity. The in vitro antifungal activities of the newly synthesized
      azoles 10p-v,x-c' were tested against Candida albicans and Candida spp. at pH 7.2
      and pH 5.6. A CoMFA model, previously derived for a series of antifungal agents
      belonging to chemically diverse families related to bifonazole, was applied to
      the new products. Because the results produced by this approach were not
      encouraging, Catalyst software was chosen to perform a new 3D-QSAR study.
      Catalyst was preferred this time because of the possibility of considering each
      compound as a collection of energetically reasonable conformations and of
      considering alternative stereoisomers. The pharmacophore model developed by
      Catalyst, named HYPO1, showed good performances in predicting the biological
      activity data, although it did not exhibit an unequivocal preference for one
      enantiomeric series of inhibitors relative to the other. One aromatic nitrogen
      with a lone pair in the ring plane (mapped by all of the considered compounds)
      and three aromatic ring features were recognized to have pharmacophoric
      relevance, whereas neither hydrogen bond acceptor nor hydrophobic features were
      found. These findings confirmed that the key interaction of azole antifungals
      with the demethylase enzyme is the coordination bond to the iron ion of the
      porphyrin system, while interactions with amino acids localized in proximity of
      heme could modulate the biological activity of diverse antifungal agents. In
      conclusion, HYPO1 conveys important information in an intuitive manner and can
      provide predictive capability for evaluating new compounds.

PMID- 12061876
TI  - From imidazoles to pyrimidines: new inhibitors of cytokine release.
AB  - On the basis of model imidazole inhibitors of cytokine release, a series of novel
      pyridinyl pyrimidine derivatives was prepared and tested on their ability to
      inhibit the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin
      1beta (IL-1beta) from peripheral blood mononuclear cells (PBMC) and human whole
      blood. In the pyrimidine series, structure-activity relationships (SARs) similar
      to those of the imidazole series were found, although generally pyrimidine
      compounds were less potent. Modification of the substituent at the 2 position of
      the pyrimidine led to the most active compound 14 which inhibited release of TNF
      alpha (IC(50) = 3.2 microM) and IL-1beta (IC(50) = 2.3 microM) from PBMC as
      effectively as the model imidazole inhibitor ML 3163 (TNF-alpha, IC(50) = 3.7
      microM; IL-1beta, IC(50) = 0.9 microM). Screening in an isolated enzyme assay
      revealed both imidazole and pyrimidine compounds as inhibitors of p38 MAP
      (mitogen-activated protein) kinase.

PMID- 12061877
TI  - Design, synthesis, and evaluation of new chemosensitizers in multi-drug-resistant
      Plasmodium falciparum.
AB  - A series of new chemosensitizers (modulators) against chloroquine-resistant
      Plasmodium falciparum were designed and synthesized in an attempt to fabricate
      modulators with enhancing drug-resistant reversing efficacy and minimal side
      effects. Four aromatic amine ring systems-phenothiazine, iminodibenzyl,
      iminostilbene, and diphenylamine-were examined. Various tertiary amino groups
      including either noncyclic or cyclic aliphatic amines were introduced to explore
      the steric tolerance at the end of the side chain. The new compounds showed
      better drug-resistant reversing activity in chloroquine-resistant than in
      mefloquine-resistant cell lines and were generally more effective against
      chloroquine-resistant P. falciparum isolates from Southeast Asian (W2 and
      TM91C235) than those from South America (PC49 and RCS). Structure-activity
      relationship studies revealed that elongation of the alkyl side chain of the
      molecule retained the chemosensitizing activity, and analogues with four-carbon
      side chains showed superior activity. Furthermore, new modulators with
      phenothiazine ring exhibited the best chemosensitizing activity among the four
      different ring systems examined. Terminal amino function has limited steric
      tolerance as evidenced by the dramatic lose of the modulating activity, when the
      size of substituent at the amino group increases. The best new modulator
      synthesized in this study possesses all three optimized structural features,
      which consist of a phenothiazine ring and a pyrrolidinyl group joined by a four
      carbon alkyl bridge. The fractional inhibitory concentration (FIC) index of the
      best compound is 0.21, which is superior to that of verapamil (0.51), one of the
      best-known multi-drug-resistant reversing agents. Some of the analogues displayed
      moderate intrinsic in vitro antimalarial activity against a W-2 clone of P.
      falciparum.

PMID- 12061879
TI  - SMall Molecule Growth 2001 (SMoG2001): an improved knowledge-based scoring
      function for protein-ligand interactions.
AB  - Computational lead design procedures require fast and accurate scoring functions
      to rank millions of generated virtual ligands for protein targets. In this
      article, we present an improved version of the SMoG scoring function, called
      SMoG2001. This function is based on a knowledge-based approach-that is, the free
      energy parameters are derived from the observed frequencies of atom-atom contacts
      in the database of three-dimensional structures of protein-ligand complexes via a
      procedure based on statistical mechanics. We obtained the statistics from the set
      of 725 complexes. SMoG2001 reproduces the experimental binding constants of the
      majority of 119 complexes of the testing set with good accuracy. On similar
      testing sets, SMoG2001 performs better than two other widely used scoring
      functions, PMF and SCORE1(LUDI), and comparably to DrugScore. SMoG2001 poorly
      predicts the affinities of ligands interacting via quantum mechanical forces with
      metal ions and ligands that are large and flexible. We attribute significant
      improvement in accuracy over previous versions of the SMoG scoring function to a
      better description of the reference state-that is, the state of no interactions.

PMID- 12061878
TI  - Design and quantitative structure-activity relationship of 3-amidinobenzyl-1H
      indole-2-carboxamides as potent, nonchiral, and selective inhibitors of blood
      coagulation factor Xa.
AB  - A series of 138 nonchiral 3-amidinobenzyl-1H-indole-2-carboxamides and analogues
      as inhibitors of the blood coagulation enzyme factor Xa (fXa) were designed,
      synthesized, and investigated by X-ray structure analysis and 3D quantitative
      structure-activity relationship (QSAR) studies (CoMFA, CoMSIA) in order to
      identify important protein-ligand interactions responsible for biological
      affinity and selectivity. Several compounds from this series are highly potent
      and selective inhibitors of this important enzyme linking extrinsic and intrinsic
      coagulation pathways. To rationalize biological affinity and to provide
      guidelines for further design, all compounds were docked into the factor Xa
      binding site. Those docking studies were based on X-ray structures of factor Xa
      in complex with literature-known inhibitors. It was possible to validate those
      binding modes by four X-ray crystal structures of representative ligands in
      factor Xa, while one ligand was additionally crystallized in trypsin to
      rationalize requirements for selective factor Xa inhibition. The 3D-QSAR models
      based on a superposition rule derived from these docking studies were validated
      using conventional and cross-validated r(2) values using the leave-one-out method
      and repeated analyses using two randomly chosen cross-validation groups plus
      randomization of biological activities. This led to consistent and highly
      predictive 3D-QSAR models with good correlation coefficients for both CoMFA and
      CoMSIA, which were found to correspond to experimentally determined factor Xa
      binding site topology in terms of steric, electrostatic, and hydrophobic
      complementarity. Subsets selected as smaller training sets using 2D fingerprints
      and maximum dissimilarity methods resulted in 3D-QSAR models with remarkable
      correlation coefficients and a high predictive power. The final quantitative SAR
      information agrees with all experimental data for the binding topology and thus
      provides reasonable activity predictions for novel factor Xa inhibitors.

PMID- 12061880
TI  - Synthesis and biological evaluation of analogues of the peptaibol ampullosporin
      A.
AB  - A series of analogues of the fungal peptaibol type metabolite ampullosporin A
      containing modifications in the C and N terminus as well as alpha-aminoisobutyric
      acid (Aib) substitutions in different positions of the peptide were synthesized
      by solid phase synthesis using the 9-fluorenylmethyloxycarbonyl strategy.
      Depending on the sequence position, couplings were performed with 2-(1H
      benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate/1
      hydroxybenzotriazole and tetramethylfluoroformamidinium hexafluorophosphate,
      respectively. The structures of the target peptides were analyzed by electrospray
      ionization mass spectrometry and chromatographic methods (high-performance liquid
      chromatography, thin-layer chromatography). The biological activities of these
      compounds have been evaluated by assaying their potencies for the induction of
      pigment formation on the fungus Phoma destructiva as well as for the induction of
      hypothermia and inhibition of locomotoric activity in mice and were compared to
      the naturally occurring ampullosporins. Native ampullosporin A and analogues with
      C-terminal Leu or Leu-NH(2) showed comparable activity in the pigmentation assay.
      Similarly, the ampullosporin A analogues with N-terminal aromatic amino acid
      residues, such as D-Trp and Tic, also have high potency for pigment formation.
      The peptides containing structural modifications of ampullosporin A by systematic
      replacement of Aib by Ala (Ala scan) displayed moderate or high activity in the
      pigmentation assay, whereas simultaneous substitution of all Aib residues by Ala
      and Ile, respectively, or by insertion of nonaromatic residues into position 1
      resulted in a loss of the effect on P. destructiva. Most of the compounds with no
      or weak activity in the microbial assay were not active in the hypothermic test,
      too, except the compound with 1-amino-1-cyclohexane carboxylic acid in position 4
      instead of Aib. However, only a few compounds with high potency for pigmentation
      induction were found to produce strong hypothermia in mice. Thus, in contrast to
      the native ampullosporins, we succeeded to a certain degree in differentiation of
      the bioactivities with our synthetic analogues.

PMID- 12061881
TI  - Synthesis and structure-affinity-activity relationships of novel benzofuran
      derivatives as MT(2) melatonin receptor selective ligands.
AB  - A series of N-(2-phenylbenzofuran-3-yl) ethyl amide and N-(2-arylalkylbenzofuran
      3-yl) ethyl amide derivatives were synthesized and evaluated as melatonin
      receptor ligands. The affinity of each compound for the two MT(1) and MT(2)
      melatonin receptor subtypes was determined by binding studies using 2
      [(125)I]iodomelatonin on human embryonic kidney cell line HEK293 membrane
      homogenates. The intrinsic activity of the most interesting compounds was
      evaluated on the [(35)S]GTPgammaS binding assay. Introduction of a 2-phenyl
      substituent in the C-2 benzofuran position leads to an agonist compound, 10q,
      which binds more strongly than melatonin itself to both MT(1) and MT(2) subtypes.
      On the other hand, a 2-benzyl group in the same position allows MT(2) antagonist
      selective ligands to be obtained. The MT(2) selectivity and antagonist potency
      can be modulated with suitable modifications on the N-acyl and benzyl
      substituents, and the most selective compounds 10c and 19 show affinity ratios of
      123 and 192, respectively, and bind to the MT(2) subtype similarly to melatonin
      itself (0.1 nM). Nevertheless, 10c acts as an MT(1) and MT(2) antagonist, whereas
      19 is a partial agonist.

PMID- 12061882
TI  - Structure-activity relationships of the melanocortin tetrapeptide Ac-His-DPhe-Arg
      Trp-NH(2) at the mouse melanocortin receptors. 1. Modifications at the His
      position.
AB  - The melanocortin pathway is an important participant in obesity and energy
      homeostasis. The centrally located melanocortin-3 and melanocortin-4 receptors
      (MC3R, MC4R) are involved in the metabolic and food intake aspects of energy
      homeostasis and are stimulated by melanocortin agonists such as alpha-melanocyte
      stimulation hormone (alpha-MSH). The melanocortin agonists contain the putative
      message sequence "His-Phe-Arg-Trp", and it has been well documented that
      inversion of chirality of the Phe to DPhe results in a dramatic increase in
      melanocortin receptor potency. Herein, we report a tetrapeptide library based on
      the template Ac-His-DPhe-Arg-Trp-NH(2), consisting of 17 members that have been
      modified at the His(6) position (alpha-MSH numbering) and pharmacologically
      characterized for agonist activity at the mouse melanocortin receptors MC1R,
      MC3R, MC4R, and MC5R. These studies provide further experimental evidence that
      the His(6) position can determine MC4R versus MC3R agonist selectivity and that
      chemically nonreactive side chains may be substituted for the imidazole ring
      (generally needs to be side chain protected in synthetic schemes) in the design
      of MC4R-selective, small-molecule, non-peptide agonists. Specifically, the
      tetrapeptide containing the amino-2-naphthylcarboxylic acid (Anc) amino acid at
      the His position resulted in a potent agonist at the mMC4R (EC(50) = 21 nM), was
      a weak mMC3R micromolar antagonist (pA(2) = 5.6, K(i) = 2.5 microM), and
      possessed >4700-fold agonist selectivity for the MC4R versus the MC3R.
      Substitution of the His(6) amino acid in the tetrapeptide template by the Phe,
      Anc, 3-(2-thienyl)alanine (2Thi), and 3-(4-pyridinyl)alanine (4-Pal) resulted in
      equipotency or only up to a 7-fold decrease in potency, compared to the His(6)
      containing tetrapeptide at the mMC4R, demonstrating that these amino acid side
      chains may be substituted for the imidazole in the design of MC4R-selective non
      peptide molecules.

PMID- 12061883
TI  - Quantitative structure-activity relationship analysis of functionalized amino
      acid anticonvulsant agents using k nearest neighbor and simulated annealing PLS
      methods.
AB  - We report the development of rigorously validated quantitative structure-activity
      relationship (QSAR) models for 48 chemically diverse functionalized amino acids
      with anticonvulsant activity. Two variable selection approaches, simulated
      annealing partial least squares (SA-PLS) and k nearest neighbor (kNN), were
      employed. Both methods utilize multiple descriptors such as molecular
      connectivity indices or atom pair descriptors, which are derived from two
      dimensional molecular topology. QSAR models with high internal accuracy were
      generated, with leave-one-out cross-validated R(2) (q(2)) values ranging between
      0.6 and 0.8. The q(2) values for the actual dataset were significantly higher
      than those obtained for the same dataset with randomly shuffled activity values,
      indicating that models were statistically significant. The original dataset was
      further divided into several training and test sets, with highly predictive
      models providing q(2) values greater than 0.5 for the training sets and R(2)
      values greater than 0.6 for the test sets. These models were capable of
      predicting with reasonable accuracy the activity of 13 novel compounds not
      included in the original dataset. The successful development of highly predictive
      QSAR models affords further design and discovery of novel anticonvulsant agents.

PMID- 12061884
TI  - N-Substituted 4-amino-3,3-dipropyl-2(3H)-furanones: new positive allosteric
      modulators of the GABA(A) receptor sharing electrophysiological properties with
      the anticonvulsant loreclezole.
AB  - 1,4-Addition of benzylamine to 2(5H)-furanone followed by dialkylation of the 3
      position with allylbromide gave (+/-)-4-benzyl-3,3-diallyl-2(3H)-furanone (8),
      which served as the intermediate for the synthesis of various N-substituted 4
      amino-3,3-dipropyl-2(3H)-furanones (+/-)-9a-l. The compounds were evaluated for
      their capacity to potentiate or inhibit GABA-evoked currents in Xenopus laevis
      oocytes expressing recombinant alpha1beta2gamma2 GABA(A) receptors. The benzyl,
      ethyl, and allyl carbamates ((R)-9a (100 microM), (+/-)-9b (100 microM), (+/-)-9c
      (200 microM)) stimulated GABA currents by 279 +/- 47%, 426 +/- 8%. and 765 +/-
      61%, respectively, while the phenylcarboxamide (+/-)-9f (200 microM) stimulated
      currents by 420 +/- 33%. Concentration-response studies showed that compound 9c
      was approximately twice as potent in stimulating GABA currents as alpha-EMTBL
      (2), the most potent 3,3-dialkylbutyrolactone known to date. On the other hand,
      the N-sulfonyl analogues were much less active or even inhibited GABA-evoked
      currents. In vitro radioligand displacement studies on rat brain membranes showed
      that these compounds did not bind to the benzodiazepine or GABA recognition sites
      of the GABA(A) receptor. However, these compounds generally weakly displaced
      [(35)S]-TBPS (approximately 50% displacement at 100 microM), though potencies did
      not correlate with GABA current potentiation. Results obtained with alpha1beta1
      and mutant alpha1beta2N265S receptors, which compared to alpha1beta2 receptors
      are both much less sensitive to current stimulation produced by the
      anticonvulsant loreclezole, suggest that at least some of these
      aminobutyrolactones, (e.g., 9a, 9c), and interestingly also alpha-EMTBL, share
      stimulatory properties with loreclezole.

PMID- 12061885
TI  - Structural features of azidopyridinyl neonicotinoid probes conferring high
      affinity and selectivity for mammalian alpha4beta2 and Drosophila nicotinic
      receptors.
AB  - The higher toxicity of neonicotinoid insecticides such as N-(6-chloropyridin-3
      ylmethyl)-2-nitroiminoimidazolidine (imidacloprid) to insects than mammals is due
      in large part to target site specificity at the corresponding nicotinic
      acetylcholine receptors (nAChRs). We propose that neonicotinoids with a
      protonated N-unsubstituted imine or equivalent substituent recognize the anionic
      subsite of the mammalian alpha4beta2 nAChR whereas the negatively charged (delta(
      )) tip of the neonicotinoid insecticides interacts with a putative cationic
      subsite of the insect nAChR. This hypothesis can be tested by using two
      photoaffinity probes that differ only in the N-unsubstituted imine vs negatively
      charged (delta(-)) tip. Synthesis methodology was developed for compounds
      combining three moieties: pyridin-3-ylmethyl or 6-chloropyridin-3-ylmethyl and
      their 4- and 5-azido analogues; imidazolidine, 4-imidazoline or 4-thiazoline; and
      N-unsubstituted imine, nitroimine, cyanoimine, or nitromethylene. Structure
      activity studies compared displacement of [(3)H]nicotine binding in mammalian
      alpha4beta2 nAChR and [(3)H]imidacloprid binding in Drosophila nAChR. Preferred
      compounds are N-(5-azido-6-chloropyridin-3-ylmethyl) with 2-iminothiazoline for
      alpha4beta2 (K(i) = 0.47 nM) and with 2-nitroiminothiazoline or 2
      nitromethyleneimidazolidine for Drosophila (K(i) = 0.72-3.9 nM).

PMID- 12061886
TI  - Synthesis and evaluation of a novel series of 2-chloro-5-((1-methyl-2-(S)
      pyrrolidinyl)methoxy)-3-(2-(4-pyridinyl)vinyl)pyridine analogues as potential
      positron emission tomography imaging agents for nicotinic acetylcholine
      receptors.
AB  - Reportedly, 2-[(18)F]fluoro-A-85380, 1, a promising radiotracer for imaging the
      nicotinic acetylcholine receptor (nAChR) by positron emission tomography (PET) in
      humans, exhibits slow penetration through the blood-brain barrier (BBB) due to
      its low lipophilicity. A ligand for nAChRs with greater lipophilicity than that
      of 1 would be potentially more favorable for PET imaging of nAChR due to its
      faster penetration through the BBB. Herein, a novel series of compounds has been
      developed based on the high affinity ligand for nAChRs, 2-chloro-5-((1-methyl-2
      (S)-pyrrolidinyl)methoxy)-3-(2-(4-pyridinyl)vinyl)pyridine, 3b. The in vitro
      binding affinities for the new series were found to be in the range of K(i) = 9
      331 pM. A molecular modeling study showed differences in the comformational
      profiles and the electronic properties of these compounds, which provides further
      insight into the structure-activity relationships at nAChR. Lipophilicities of
      the compounds 3b-6b have been found to be substantially higher than that of 1. As
      a result, compounds 3b-6b might exhibit a faster penetration through the BBB than
      the less lipophilic 1. The N-methyl derivatives 3b and 6b demonstrated very high
      affinities at nAChRs (K(i) = 28 and 23 pM, respectively) and will be targets for
      development of (11)CH(3)-labeled derivatives as radiotracers for PET imaging of
      nAChRs.

PMID- 12061887
TI  - Acylating agents as enzyme inhibitors and understanding their reactivity for drug
      design.
AB  - A series of bicyclic trans-fused gamma-lactones and gamma-lactams have been
      previously described for the inhibition of human neutrophil elastase and as
      possible development candidates. During the discovery program, it had been
      assumed that their acylating power was due in part to the inherent strain energy
      in the bicyclic structure that was released upon ring opening. This is now shown
      not to be the case, and in fact, these compounds are no more reactive than simple
      but analogous gamma-lactams and gamma-lactones. The strain energy is not released
      in the transition state for alkaline hydrolysis or alcoholysis because the
      reaction proceeds with rate-limiting formation of the tetrahedral intermediate. A
      reactivity index of k(OH) is proposed as a simple guide to determine the
      usefulness of a potential inhibitor as an enzyme acylating agent.

PMID- 12061889
TI  - Prediction of volume of distribution values in humans for neutral and basic drugs
      using physicochemical measurements and plasma protein binding data.
AB  - We present a method for the prediction of volume of distribution in humans, for
      neutral and basic compounds. It is based on two experimentally determined
      physicochemical parameters, ElogD(7.4) and f(i(7.4)), the latter being the
      fraction of compound ionized at pH 7.4 and on the fraction of free drug in plasma
      (f(u)). The fraction unbound in tissues (f(ut)), determined via a regression
      analysis from 64 compounds using the parameters described, is then used to
      predict VD(ss) via the Oie-Tozer equation. Accuracy of this method was determined
      using a test set of 14 compounds, and it was demonstrated that human VD(ss)
      values could be predicted, on average, within or very close to 2-fold of the
      actual value. The present method is as accurate as reported methods based on
      animal pharmacokinetic data, using a similar set of compounds, and ranges between
      1.62 and 2.20 as mean-fold error. This method has the advantage of being amenable
      to automation, and therefore fast throughput, it is compound and resources
      sparing, and it offers a rationale for the reduction of the use of animals in
      pharmacokinetic studies. A discussion of the potential errors that may be
      encountered, including errors in the determination of f(u), is offered, and the
      caveats about the use of computed vs experimentally determined logD and pK(a)
      values are addressed.

PMID- 12061888
TI  - Structure-activity relationship for enhancement of paracellular permeability
      across Caco-2 cell monolayers by 3-alkylamido-2-alkoxypropylphosphocholines.
AB  - Paracellular permeability enhancers have been used to improve the oral
      bioavailability of hydrophilic drugs; however, the mechanism of action of many
      enhancers is poorly understood. In this study, highly potent enhancers of
      paracellular permeability were identified in the 3-alkylamido-2
      alkoxypropylphosphocholine series, and a structure-activity relationship was
      developed for enhancement of paracellular permeability across Caco-2 cell
      monolayers. Compounds with short (<5 carbons) hydrocarbon chains at both C-2 and
      C-3 were generally inactive. The potency exhibited a parabolic relationship with
      respect to the chain length at either C-2 or C-3. Linear molecules (i.e.,
      compounds with a short hydrocarbon chain at C-2 or C-3 and a long hydrocarbon
      chain on C-3 or C-2, respectively) were more potent than the corresponding
      branched molecules with the same carbon load. The efficacy of 3-alkylamido-2
      alkoxypropylphosphocholines as enhancers of paracellular permeability was not
      dependent on their existence in micellar form or their ability to alter the
      fluidity of cell membrane. Previously, a correlation between the potency of
      alkylphosphocholines as enhancers of paracellular permeability and the inhibitors
      of phospholipase C (PLC) was established in Madine Darby canine kidney (MDCK)
      cell monolayers. The potencies of selected 3-alkylamido-2
      alkoxypropylphosphocholines as inhibitors of PLC and enhancers of paracellular
      permeability fit well into this correlation. Therefore, phosphocholines are
      likely to increase paracellular permeability by modulating the signal
      transduction pathway initiated by a PLC-catalyzed reaction rather than by
      physically altering the cell membrane.

PMID- 12061890
TI  - Structurally simple trichostatin A-like straight chain hydroxamates as potent
      histone deacetylase inhibitors.
AB  - A series of new, structurally simple trichostatin A (TSA)-like straight chain
      hydroxamates were prepared and evaluated for their ability to inhibit partially
      purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as
      8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar
      IC(50) values, comparable to natural TSA. These compounds induce hyperacetylation
      of histones in T24 human cancer cells and significantly inhibit proliferation in
      various human cancer cells. They also induce expression of p21 and cause cell
      cycle blocks in human cancer cells. In this paper, we describe the synthesis of
      these new compounds as well as structure-activity relationship results from
      enzyme inhibition and alterations in cellular function.

PMID- 12061892
TI  - A 13C-NMR study of the inhibition of papain by a dipeptide-glyoxal inhibitor.
AB  - Z-Phe-Ala-glyoxal (where Z is benzyloxycarbonyl) has been synthesized and shown
      to be a competitive inhibitor of papain with a K(i)=3.30+/-0.25 nM. (13)C-NMR has
      been used to show that in aqueous media, Z-Phe-[2-(13)C]Ala-glyoxal gives signals
      at 207.7 p.p.m. and 96.3 p.p.m. showing that both the alpha-keto carbon and its
      hydrate are present. When this inhibitor is bound to papain a single signal at
      209.7 p.p.m. is observed due to the (13)C-enriched carbon. This demonstrates that
      the glyoxal alpha-keto carbon is not hydrated when it is bound to papain and that
      it does not form a thiohemiketal with the thiol group of Cys-25. Z-Phe-[1
      (13)C]Ala-glyoxal has also been synthesized and its aldehyde carbon is fully
      hydrated in aqueous solution giving signals at 88.7 p.p.m. and 90.2 p.p.m. when
      the alpha-keto carbon and its hydrate are present respectively. When this
      inhibitor is bound to papain a single signal at 71.04 p.p.m. was observed due to
      the (13)C-enriched carbon showing that the (13)C-enriched aldehyde carbon forms a
      thiohemiacetal with Cys-25.

PMID- 12061894
TI  - Male gametophyte development in bread wheat (Triticum aestivum L.): molecular,
      cellular, and biochemical analyses of a sporophytic contribution to pollen wall
      ontogeny.
AB  - Bread wheat (hexaploid AABBDD genome; 16 billion basepairs) is a genetically
      complex, self-pollinating plant with bisexual flowers that produce short-lived
      pollen. Very little is known about the molecular biology of its gametophyte
      development despite a longstanding interest in hybrid seeds. We present here a
      comprehensive characterization of three apparently homeologous genes (TAA1a,
      TAA1b and TAA1c) and demonstrate their anther-specific biochemical function.
      These eight-exon genes, found at only one copy per haploid complement in this
      large genome, express specifically within the sporophytic tapetum cells. The
      presence of TAA1 mRNA and protein was evident only at specific stages of pollen
      development as the microspore wall thickened during the progression of free
      microspores into vacuolated-microspores. This temporal regulation matched the
      assembly of wall-impregnated sporopollenin, a phenylpropanoid-lipid polymer
      containing very long chain fatty alcohols (VLCFAlc), described in the literature.
      Our results establish that sporophytic genes contribute to the production of
      fatty alcohols: Transgenic expression of TAA1 afforded production of long/VLCFAlc
      in tobacco seeds (18 : 1; 20 : 1; 22 : 1; 24 : 0; 26 : 0) and in Escherichia coli
      (14 : 0; 16 : 0; 18 : 1), suggesting biochemical versatility of TAA1 with respect
      to cellular milieu and substrate spectrum. Pollen walls additionally contain
      fatty alcohols in the form of wax esters and other lipids, and some of these
      lipids are known to play a role in the highly specific sexual interactions at the
      pollen-pistil interface. This study provides a handle to study these and to
      manipulate pollen traits, and, furthermore, to understand the molecular biology
      of fatty alcohol metabolism in general.

PMID- 12061896
TI  - The cycloidea gene can respond to a common dorsoventral prepattern in
      Antirrhinum.
AB  - Dorsoventral asymmetry in flowers of Antirrhinum depends on expression of the
      cycloidea gene in dorsal regions of floral meristems. To determine how cycloidea
      might be regulated we analysed its expression in several contexts. We show that
      cycloidea is activated shortly after floral induction, and that in addition to
      flowers, cycloidea can be asymmetrically expressed in shoots, even though these
      shoots show no marked dorsoventral asymmetry. Shoots expressing cycloidea include
      secondary branches lying just below the inflorescence, and shoots of floricaula
      mutants. Asymmetric cycloidea expression may also be observed within organ
      primordia, such as the sepals of terminal flowers produced by centroradialis
      mutants. Later expression of cycloidea within flowers can be modified by
      mutations in organ identity genes. Taken together, the results suggest that
      cycloidea can respond to a common dorsoventral pre-pattern in the apex and that
      the specific effects of cycloidea on the flower depend on interactions with
      floral-specific genes.

PMID- 12061891
TI  - Phagosome maturation: aging gracefully.
AB  - Foreign particles and apoptotic bodies are eliminated from the body by phagocytic
      leucocytes. The initial stage of the elimination process is the internalization
      of the particles into a plasma membrane-derived vacuole known as the phagosome.
      Such nascent phagosomes, however, lack the ability to kill pathogens or to
      degrade the ingested targets. These properties are acquired during the course of
      phagosomal maturation, a complex sequence of reactions that result in drastic
      remodelling of the phagosomal membrane and contents. The determinants and
      consequences of the fusion and fission reactions that underlie phagosomal
      maturation are the topic of this review.

PMID- 12061895
TI  - Six active phage-type RNA polymerase genes in Nicotiana tabacum.
AB  - In higher plants, a small nuclear gene family encodes mitochondrial as well as
      chloroplast RNA polymerases (RNAP) homologous to the bacteriophage T7-enzyme. The
      Arabidopsis genome contains three such RpoT genes, while in monocotyledonous
      plants only two copies have been found. Analysis of Nicotiana tabacum, a natural
      allotetraploid, identified six different RpoT sequences. The study of the
      progenitor species of tobacco, N. sylvestris and N. tomentosiformis, uncovered
      that the sequences represent two orthologous sets each of three RpoT genes
      (RpoT1, RpoT2 and RpoT3). Interestingly, while the organelles are inherited
      exclusively from the N. sylvestris maternal parent, all six RpoT genes are
      expressed in N. tabacum. GFP-fusions of Nicotiana RpoT1 revealed mitochondrial
      targeting properties. Constructs containing the amino-terminus of RpoT2 were
      imported into mitochondria as well as into plastids. Thus, the dual-targeting
      feature, first described for Arabidopsis RpoT;2, appears to be conserved among
      eudicotyledonous plants. Tobacco RpoT3 is targeted to chloroplasts and the RNA is
      differentially expressed in plants lacking the plastid-encoded RNAP. Remarkably,
      translation of RpoT3 mRNA has to be initiated at a CUG codon to generate a
      functional plastid transit peptide. Thus, besides AGAMOUS in Arabidopsis,
      Nicotiana RpoT3 provides a second example for a non-viral plant mRNA that is
      exclusively translated from a non-AUG codon.

PMID- 12061897
TI  - The ABC transporter SpTUR2 confers resistance to the antifungal diterpene
      sclareol.
AB  - PDR5-like proteins represent one group of the ABC superfamily of transporters.
      Members of this group are present in plants and, due to the function of PDR5
      related proteins in fungi in the excretion of xenobiotics (including antifungal
      agents), it has been proposed that they might play a similar role in plants in
      the response to and detoxification of herbicides and fungicides. However, until
      now no functional data has been presented showing an altered plant response to
      any herbicide or fungicide as a result of manipulating the expression of a PDR5
      like gene in plants. In this paper, we show that the plant SpTUR2 PDR5-like ABC
      transporter is localised to the plasma membrane and that expression of this
      protein in Arabidopsis leads to the acquisition of resistance to the diterpenoid
      antifungal agent sclareol. These data both define a possible endogenous substrate
      for this transporter and highlight the potential of manipulating plant chemical
      resistance via modulating the expression of specific PDR5-like transporters.

PMID- 12061893
TI  - New perspectives in the regulation of hepatic glycolytic and lipogenic genes by
      insulin and glucose: a role for the transcription factor sterol regulatory
      element binding protein-1c.
AB  - The regulation of hepatic glucose metabolism has a key role in whole-body energy
      metabolism, since the liver is able to store (glycogen synthesis, lipogenesis)
      and to produce (glycogenolysis, gluconeogenesis) glucose. These pathways are
      regulated at several levels, including a transcriptional level, since many of the
      metabolism-related genes are expressed according to the quantity and quality of
      nutrients. Recent advances have been made in the understanding of the regulation
      of hepatic glycolytic, lipogenic and gluconeogenic gene expression by pancreatic
      hormones, insulin and glucagon and glucose. Here we review the role of the
      transcription factors forkhead and sterol regulatory element binding protein-1c
      in the inductive and repressive effects of insulin on hepatic gene expression,
      and the pathway that leads from glucose to gene regulation with the recently
      discovered carbohydrate response element binding protein. We discuss how these
      transcription factors are integrated in a regulatory network that allows a fine
      tuning of hepatic glucose storage or production, and their potential importance
      in metabolic diseases.

PMID- 12061898
TI  - Decreased Rubisco activity leads to dramatic changes of nitrate metabolism, amino
      acid metabolism and the levels of phenylpropanoids and nicotine in tobacco
      antisense RBCS transformants.
AB  - Tobacco transformants that express an antisense RBCS construct were used to
      investigate the consequences of a lesion in photosynthetic carbon metabolism for
      nitrogen metabolism and secondary metabolism. The results show that an inhibition
      of photosynthesis and decrease in sugar levels leads to a general inhibition of
      nitrogen metabolism, and dramatic changes in the levels of secondary metabolites.
      The response was particularly clear in plants that received excess nitrogen. In
      these conditions, a decrease of Rubisco activity led to an inhibition of nitrate
      reductase activity, accumulation of nitrate, a decrease of amino acid levels that
      was larger than the decrease of sugars, and a large decrease of chlorogenic acid
      and of nicotine, which are the major carbon- and nitrogen-rich secondary
      metabolites in tobacco leaves, respectively. Similar changes were seen when
      nitrogen-replete wild-type tobacco was grown in low light. The inhibition of
      nitrogen metabolism was partly masked when wild-type plants and antisense RBCS
      transformants were compared in marginal or in limiting nitrogen, because the
      lower growth rate of the transformants alleviated the nitrogen deficiency,
      leading to an increase of amino acids. In these conditions, chlorogenic acid
      always decreased but the decrease of nicotine was ameliorated or reversed. When
      the changes in internal pools are compared across all the genotypes and growth
      conditions, two conclusions emerge. First, decreased levels of primary
      metabolites lead to a dramatic decrease in the levels of secondary metabolites.
      Second, changes of the amino acid : sugar ratio are accompanied by changes of the
      nicotine:chlorogenic acid ratio.

PMID- 12061899
TI  - Maize DRE-binding proteins DBF1 and DBF2 are involved in rab17 regulation through
      the drought-responsive element in an ABA-dependent pathway.
AB  - The abscisic acid-responsive gene rab17 of maize is expressed during late
      embryogenesis, and is induced by ABA and desiccation in embryo and vegetative
      tissues. ABRE and DRE cis-elements are involved in regulation of the gene by ABA
      and drought. Using yeast one-hybrid screening, we isolated two cDNAs encoding two
      new DRE-binding proteins, designated DBF1 and DBF2, that are members of the
      AP2/EREBP transcription factor family. Analysis of mRNA accumulation profiles
      showed that DBF1 is induced during maize embryogenesis and after desiccation,
      NaCl and ABA treatments in plant seedlings, whereas the DBF2 mRNA is not induced.
      DNA-binding preferences of DBFs were analysed by electrophoretic mobility shift
      assays, and showed that both DBF1 and DBF2 bound to the wild-type DRE2 element,
      but not to the DRE2 mutant or to the DRE1 element which differs only in a single
      nucleotide. Transactivation activity using particle bombardment showed that DBF1
      functioned as activator of DRE2-dependent transcription of rab17 promoter by ABA,
      whereas DBF2 overexpression had a repression action downregulating not only the
      basal promoter activity, but also the ABA effect. These results show that ABA
      plays a role in the regulation of DBF activity, and suggests the existence of an
      ABA-dependent pathway for the regulation of genes through the C-repeat/DRE
      element.

PMID- 12061901
TI  - Plant RanGAPs are localized at the nuclear envelope in interphase and associated
      with microtubules in mitotic cells.
AB  - In animals and yeast, the small GTP-binding protein Ran has multiple functions -
      it is involved in mediating (i) the directional passage of proteins and RNA
      through the nuclear pores in interphase cells; and (ii) the formation of spindle
      asters, the polymerization of microtubules, and the re-assembly of the nuclear
      envelope in mitotic cells. Nucleotide binding of Ran is modulated by a series of
      accessory proteins. For instance, the hydrolysis of RanGTP requires stimulation
      by the RanGTPase protein RanGAP. Here we report the complementation of the yeast
      RanGAP mutant rna1 with Medicago sativa and Arabidopsis thaliana cDNAs encoding
      RanGAP-like proteins. Confocal laser microscopy of Arabidopsis plants
      overexpressing chimeric constructs of GFP with AtRanGAP1 and 2 demonstrated that
      the fusion protein is localized to patchy areas at the nuclear envelope of
      interphase cells. In contrast, the cellular distribution of RanGAPs in
      synchronized tobacco cells undergoing mitosis is characteristically different.
      Double-immunofluorescence shows that RanGAPs are co-localized with spindle
      microtubules during anaphase, with the microtubular phragmoplast and the surface
      of the daughter nuclei during telophase. Co-assembly of RanGAPs with tubulin
      correlates with these in vivo observations. The detected localization pattern is
      consistent with the postulated function of plant RanGAPs in the regulation of
      nuclear transport during interphase, and suggests a role for these proteins in
      the organization of the microtubular mitotic structures.

PMID- 12061900
TI  - A role for nuclear localised proteasomes in mediating auxin action.
AB  - A number of important cellular events in animals and yeast are regulated by
      protein degradation, and it is becoming apparent that such regulated proteolysis
      is involved in many facets of plant physiology and development. We have
      investigated the role of protein degradation by proteasomes in plants using
      NtPSA1, a tobacco gene that is predominantly expressed in young developing
      tobacco tissues and has extensive homology to yeast and human alpha-type
      proteasome subunit genes. The NtPSA1 cDNA was used to complement a lethal
      mutation of the yeast PRC1 alpha subunit gene indicating that NtPSA1 encodes a
      functional proteasome subunit, and transient expression of an NtPSA1::GUS protein
      fusion in onion cells confirmed that the nuclear localisation signal that is
      present in the NtPSA1 peptide sequence is active in plant cells. Plants
      transformed with an antisense NtPSA1 gene had reduced levels of NtPSA1 mRNA and
      exhibited reduced apical dominance. In addition, these low NtPSA1 plants
      displayed several morphological defects associated with auxin resistance such as
      reduced stamen length, and showed increased tolerance to high concentrations of
      auxin. These results support a role for nuclear localised proteasomes in floral
      development and auxin responses.

PMID- 12061902
TI  - HFR1, a phytochrome A-signalling component, acts in a separate pathway from HY5,
      downstream of COP1 in Arabidopsis thaliana.
AB  - HFR1, a basic helix-loop-helix protein, is known to be required for a subset of
      phytochrome A (phyA)-dependent photoresponses. To investigate the role of HFR1 in
      light signalling, we have examined the genetic interaction between HFR1 and HY5,
      a positive regulator of light signalling, and COP1, a repressor of
      photomorphogenesis. Double mutant analysis suggests that HFR1 mediates phyA
      dependent inhibition of hypocotyl elongation independently of HY5. HFR1 was shown
      to be necessary for a subset of cop1-triggered photomorphogenic phenotypes in the
      dark, including inhibition of hypocotyl elongation, gravitropic hypocotyl growth,
      and expression of the light-inducible genes CAB and RBCS. Phenotypic analysis of
      the triple mutant cop1hy5hfr1 indicated that both HFR1 and HY5 are required for
      cop1-mediated photomorphogenic seedling development in darkness, consistent with
      their additive roles in phyA-dependent signalling. Taken together, these results
      suggest that HFR1 might act downstream of COP1, in a separate pathway from HY5,
      to mediate photomorphogenesis in Arabidopsis.

PMID- 12061903
TI  - Conformational features of crystal-surface cellulose from higher plants.
AB  - Native cellulose in higher plants forms crystalline fibrils a few nm across, with
      a substantial fraction of their glucan chains at the surface. The accepted
      crystal structures feature a flat-ribbon 21 helical chain conformation with every
      glucose residue locked to the next by hydrogen bonds from O-3' to O-5 and from O
      2 to O-6'. Using solid-state NMR spectroscopy we show that the surface chains
      have a different C-6 conformation so that O-6 is not in the correct position for
      the hydrogen bond from O-2. We also present evidence consistent with a model in
      which alternate glucosyl residues are transiently or permanently twisted away
      from the flat-ribbon conformation of the chain, weakening the O-3' - 0-5 hydrogen
      bond. Previous molecular modelling and the modelling studies reported here
      indicate that this 'translational' chain conformation is energetically feasible
      and does not preclude binding of the surface chains to the interior chains,
      because the surface chains share the axial repeat distance of the 21 helix.
      Reduced intramolecular hydrogen bonding allows the surface chains to form more
      hydrogen bonds to external molecules in textiles, wood, paper and the living
      plant.

PMID- 12061904
TI  - Development of a GFP reporter gene for Chlamydomonas reinhardtii chloroplast.
AB  - Reporter genes have been successfully used in chloroplasts of higher plants, and
      high levels of recombinant protein expression have been reported. Reporter genes
      have also been used in the chloroplast of Chlamydomonas reinhardtii, but in most
      cases the amounts of protein produced appeared to be very low. We hypothesized
      that the inability to achieve high levels of recombinant protein expression in
      the C. reinhardtii chloroplast was due to the codon bias seen in the C.
      reinhardtii chloroplast genome. To test this hypothesis, we synthesized a gene
      encoding green fluorescent protein (GFP) de novo, optimizing its codon usage to
      reflect that of major C. reinhardtii chloroplast-encoded proteins. We monitored
      the accumulation of GFP in C. reinhardtii chloroplasts transformed with the codon
      optimized GFP cassette (GFPct), under the control of the C. reinhardtii rbcL 5'-
      and 3'-UTRs. We compared this expression with the accumulation of GFP in C.
      reinhardtii transformed with a non-optimized GFP cassette (GFPncb), also under
      the control of the rbcL 5'- and 3'-UTRs. We demonstrate that C. reinhardtii
      chloroplasts transformed with the GFPct cassette accumulate approximately 80-fold
      more GFP than GFPncb-transformed strains. We further demonstrate that expression
      from the GFPct cassette, under control of the rbcL 5'- and 3'-UTRs, is
      sufficiently robust to report differences in protein synthesis based on subtle
      changes in environmental conditions, showing the utility of the GFPct gene as a
      reporter of C. reinhardtii chloroplast gene expression.

PMID- 12061905
TI  - Towards a reduction of rectal pain?

PMID- 12061906
TI  - Serotonin type-4 receptors modulate the sensitivity of intramural
      mechanoreceptive afferents of the cat rectum.
AB  - It has been suggested that serotonin (5-hydroxytryptamine) type-4 (5-HT4)
      receptors modulate the sensitivity of intrinsic afferents of the intestinal
      mucosa. We studied the involvement of 5-HT4receptors in the modulation of
      extrinsic afferent sensitivity of the intestinal wall. During distension ramps,
      mechanoreceptive rectal afferents in sacral dorsal roots were examined in
      decerebrate anaesthesia-free cats using the selective 5-HT4receptor partial
      agonist, tegaserod (HTF 919), and the 5-HT4receptor antagonist, SB 203186. The
      static discharge rate of the afferents evoked by rectal distension decreased
      after intravenous (i.v.) administration of tegaserod at intraluminal pressures
      above 30 mmHg, with the most effective reduction occurring at 50 mmHg. The effect
      was dose-dependent, with maximal reduction occurring at 1.2 mg kg-1 bodyweight,
      and could be partly reversed by i.v. administration of SB 203186. Tegaserod did
      not alter the pressure-volume relationship (compliance) of the rectum. It is
      tentatively concluded that 5-HT4receptor activation has an inhibitory effect on
      intramural mechanoreceptors in the cat's rectum. Our results are in line with the
      observation that tegaserod relieves the sensory symptoms of patients suffering
      from irritable bowel syndrome.

PMID- 12061907
TI  - Gastrointestinal perception: pathophysiological implications.
AB  - Physiological gut stimuli during the digestive process are not normally
      perceived. However, gut stimuli activate a variety of afferent pathways and in
      some circumstances may induce conscious sensations. Experimental evidence
      gathered during the past decade suggests that patients with functional gut
      disorders and unexplained abdominal symptoms may have a sensory dysfunction of
      the gut, so that physiological stimuli would induce symptoms. Assessment of
      visceral sensitivity is still poorly developed, but in analogy to somatosensory
      testing, differential stimulation of visceral afferents may be achieved by a
      combination of stimulation techniques, which may help to characterize sensory
      dysfunctions. Visceral afferent input is modulated by a series of mechanisms at
      different levels of the brain gut axis, and conceivably, a dysfunction of these
      regulatory mechanisms could cause hyperalgesia. The sensory dysfunction in
      functional patients seems associated to altered reflex activity, and both
      mechanisms may interact to produce the symptoms. Evidence of a gut sensory-reflex
      dysfunction as a common pathophysiological mechanism in different functional
      gastrointestinal disorders, would suggest that they are different forms of the
      same process, and that the clinical manifestations depend on the specific
      pathways affected.

PMID- 12061908
TI  - Compliance, tone and sensitivity of the rectum in different subtypes of irritable
      bowel syndrome.
AB  - Irritable bowel syndrome (IBS) consists of various subtypes. It is not known
      whether these subtypes share a common pathophysiology. Evaluation of motor and
      sensory function of the rectum using a barostat may help to explore a common
      pathophysiological background or differences in pathophysiology in subtypes of
      IBS. We have evaluated compliance, tone and sensitivity of the rectum, in both
      fasting state and postprandially, using a computerized barostat in 15 patients
      with diarrhoea-predominant IBS (IBS-D), 14 patients with constipation-predominant
      IBS (IBS-C) and compared the results with those obtained in 12 healthy controls.
      Rectal compliance as calculated over the steep part of the pressure-volume curve
      (17-23 mmHg) was decreased in both IBS groups (IBS-D 8.0 +/- 1.4 mL mmHg-1; IBS-C
      5.6 +/- 1.1 mL mmHg-1) compared with controls (24.7 +/- 3.5 mL mmHg-1). The
      perception of urge was increased only in IBS-D patients, whereas pain perception
      was significantly increased in both IBS groups. Spontaneous adaptive relaxation
      was decreased in IBS-D patients. Postprandially, rectal volume decreased
      significantly in the controls and in IBS-D patients, but not in IBS-C patients.
      In conclusion, both rectal motor and sensory characteristics are different
      between IBS-D and IBS-C patients. Therefore, testing of rectal visceroperception,
      adaptive relaxation and the rectal response to a meal may help distinguish groups
      of patients with different subtypes of irritable bowel syndrome.

PMID- 12061909
TI  - A nutrient drink test to assess maximum tolerated volume and postprandial
      symptoms: effects of gender, body mass index and age in health.
AB  - To assess the effects of age, gender and body mass index on the maximum tolerated
      volume of a nutrient drink and postprandial symptoms in health. Healthy
      adolescents (15 M, 15 F, aged 13-17 years) and adults (15 M, 25 F, aged 19-51
      years) ingested Ensure (1 kcal mL-1) at a rate of 30 mL min-1. The maximum
      tolerated volume was recorded. Thirty minutes later, bloating, fullness, nausea
      and pain were rated using visual analogue scales. The Mann-Whitney test was used
      for comparisons between groups using body mass index and maximum tolerated volume
      as covariates. Age-related differences in maximum tolerated volume were noted
      between adolescents and adults, and were observed in both genders. Adults had
      higher scores for bloating and pain, and lower scores for fullness. Gender
      related differences in maximum tolerated volume were noted in the group as a
      whole, and separately for adolescents and adults. Females had higher scores for
      nausea and pain. Gender and age-related differences in the maximum tolerated
      volume of a nutrient drink and postprandial symptoms should be considered in
      future studies of upper gastrointestinal symptoms in disease. Body mass index
      does not appear to influence maximum tolerated volume beyond its association with
      age and gender.

PMID- 12061910
TI  - ATP and 5-HT are the principal neurotransmitters in the descending excitatory
      reflex pathway of the guinea-pig ileum.
AB  - Neurotransmission underlying descending excitatory reflexes evoked by distension
      was studied in opened segments of guinea-pig ileum and compared with peristalsis
      in intact segments. The opened segments were distended by inflating a balloon
      against the serosa at the oral end and changes in muscle length recorded from the
      anal end. Distension elicited contractions in both circular (CM) and longitudinal
      (LM) muscle layers. Granisetron, a 5-HT(3) receptor antagonist (10 nmol L-1 to 1
      micromol L-1) reduced CM contractions (24% control), without affecting the LM.
      The P2 receptor antagonist, pyridoxal phosphate-6-azopheyl-2',4'-disulphonic acid
      (PPADS; 10 micromol L-1), reduced CM contractions to 31% and LM contractions to
      39%. Hexamethonium (500 micromol L-1) enhanced LM contractions, but had no effect
      on CM contractions. Granisetron (1 micromol L-1) had no significant effect on the
      threshold for peristaltic contractions in a modified Trendelenburg preparation,
      but decreased the decay time of these contractions by 37%. PPADS (10 micromol L
      1) had no significant effect in this preparation. Thus, the descending excitatory
      pathways to CM and LM can be distinguished pharmacologically; the former depend
      on 5-HT(3) and P2 ATP receptors, the latter are independent of 5-HT(3) receptors.
      Nicotinic receptors may have little part in either pathway. These properties
      differ from conventional peristaltic reflexes, which are effectively abolished by
      nicotinic blockade.

PMID- 12061911
TI  - Influences of pelvic floor structures and sacral innervation on the response to
      distension of the cat rectum.
AB  - The contributions to the rectal response to distension of the pelvic floor
      structures surrounding the rectum and of the sacral spinal innervation have never
      been studied. Using paralysed intercollicularly decerebrate, anaesthesia-free
      cats, we studied pressure-volume relationships during slow ramp distensions of
      the rectum. Results obtained from animals with intact pelvic cavities were
      compared with those following mobilization of the rectum from the pelvic floor
      musculature. To assess the influences of spinal outflow and afferent input,
      rectal pressure-volume relationships were measured in the mobilized rectum
      following bilateral sequential transection of the spinal roots S1 to S3, first
      dorsal, then ventral. Isolation of the rectum from the pelvic floor structures
      resulted in a decrease in balloon volume in the lower range of distension
      pressure but did not affect volumes at higher pressures. The only afferent effect
      was seen after sectioning of dorsal roots S1, which resulted in a decrease in
      balloon volume. The only efferent effect was seen after sectioning of ventral
      roots S3, which decreased balloon volume further. In conclusion, the rectal
      response to distension depends on the properties of the rectal wall. It may be
      influenced by somatic inputs, inputs from the myenteric nervous plexus, and from
      the parasympathetic and sympathetic nervous systems. Afferent inputs and spinal
      autonomic reflexes may decrease the tone of the rectal musculature during
      distension.

PMID- 12061912
TI  - Periodic colonic motor activity identified by 24-h pancolonic ambulatory
      manometry in humans.
AB  - The pattern of colonic motor activity in healthy humans has not been fully
      elucidated to date. The aim of this study was to evaluate colorectal motor
      activity employing 24-h ambulant pancolonic manometry. Ten healthy volunteers
      (6F, 4M), aged 19-31 years were studied. Motor activity was measured using two
      custom-made silicone coated catheters, each with five solid-state pressure
      transducers. No bowel preparation or sedation was used. The study period was 24
      h. A total of 232 h of recording was obtained. Sixty-three high amplitude
      propagated contractions were observed, median six per 24-h period. Low-amplitude
      colonic contractile activity showed regional and diurnal variations. Frequency of
      contraction was highest in the right colon [median 5.26 cpm (cycles per minute)],
      and transverse colon and splenic flexure (median 5.15 cpm). The interval between
      colonic motor complexes was shortest in the transverse colon and splenic flexure.
      This study introduces a new technique for the evaluation of colorectal motor
      activity. Subjects were studied in an ambulant setting in their own environment
      ensuring that this method of study is as physiological as possible. This study
      demonstrates that colonic motor activity has two main components: high amplitude
      propagated contractions and low amplitude colonic contractile activity.

PMID- 12061913
TI  - The effect of cholecystectomy on duodenojejunal motility in humans.
AB  - We hypothesized that certain gastrointestinal symptoms following cholecystectomy
      could be explained by motor disturbances. To test this hypothesis, we compared
      pre- and post-operative motor patterns between symptomatic and asymptomatic
      patients after surgery to evaluate whether some motor changes could be induced by
      gallbladder removal and associated with symptoms. Twenty-three patients were
      prospectively evaluated before and 3 months after cholecystectomy. After surgery,
      17 patients were asymptomatic and six were symptomatic. Duodenojejunal manometric
      recordings were performed for 3 h during fasting, then 3 h after a 750-kcal meal.
      Patient motor results were compared to those obtained in the duodenojejunum of 20
      healthy controls. After surgery, only a few modifications in duodenojejunal
      motility were observed compared to the preoperative period. Motor changes related
      to cholecystectomy were increase in phase III amplitude and the absence of
      progressive decrease of the duodenojejunal motor response after the meal. After
      surgery, symptomatic patients had a lower postprandial duodenal motility index
      after the meal than asymptomatic patients (P < 0.03) and more frequent propagated
      clusters of contractions (PCCs) (P < 0.02). Preoperative motor patterns
      associated with postoperative symptoms were postprandial only and included a low
      duodenal motility index (P < 0.03), and a higher number of PCCs (P < 0.02).
      Removal of the gallbladder has a limited effect on duodenojejunal motility. Few
      motor differences existed between symptomatic and asymptomatic patients after
      surgery. However, a low duodenal motor response to a meal and PCCs were often
      associated with symptoms.

PMID- 12061914
TI  - The 13C-octanoic acid breath test: validation of a new noninvasive method of
      measuring gastric emptying in rats.
AB  - Currently available rat models for measuring gastric emptying are hampered by the
      necessity to kill the animals at the end of each experiment, which makes
      repetitive testing impossible. We have developed and validated a noninvasive test
      model, adapted from the 13C-octanoic breath test in humans, for repetitive
      measurements of gastric emptying in rats. Male Wistar rats were trained on a
      fixed protocol to eat a piece of pancake doped with 1 microg 13C-octanoic acid
      after 12 h fasting, and to stay thereafter in cylindrical glass cages. Breath
      tests were performed by a fully automated system of computer-guided switching
      valves, which collected consecutive breath samples. All breath samples were
      analysed by gas chromatography and isotope mass spectrometry. The area under the
      curve (AUC) from the cumulative 13CO2 excretion from 0 to 6 h was determined by
      the trapezium method to calculate the gastric half-emptying times (t(1/2)). Inter
      day variability was determined. The effect of subcutaneous or intraperitoneal
      injection of saline was studied. The test was further validated for
      pharmacological interventions by oral administration of cisapride and parenteral
      administration of atropine, to induce, respectively. acceleration and delay of
      gastric emptying. Mean gastric emptying times +/- SD of 24 rats were 119.3 +/-
      28.2 min, 138.7 +/- 26.0 min, and 124.5 +/- 30.9 min on three different test
      days. The mean coefficient of variation of three repeated measurements in the
      same 24 rats was 17.5%. No significant differences were observed after
      subcutaneous or intraperitoneal injection of saline. In a second test series of
      eight rats, cisapride significantly accelerated gastric emptying (mean t(1/2)
      112.7 +/- 33.1 min, P < 0.05), while atropine caused a significant delay (mean
      t(1/2) 205.9 +/- 24.9 min, P < 0.05) when compared to control test results (mean
      t(1/2) 140.7 +/- 16.7 min) in the same rats. We validated the 13C-octanoic breath
      test to study gastric emptying in rats. This test method obviates the necessity
      to kill laboratory animals and allows repetitive measurements of gastric emptying
      to study its physiology or pathophysiology as well as the effect of
      pharmacological agents.

PMID- 12061915
TI  - Lower oesophageal sphincter relaxation evoked by stimulation of the dorsal motor
      nucleus of the vagus in ferrets.
AB  - An understanding of the neural control of lower oesophageal sphincter (LOS)
      relaxation is clinically relevant because transient LOS relaxations (TLOSRs) are
      a mechanism of acid reflux into the oesophagus. Preganglionic motor neurones
      innervating the LOS are localized in the dorsal motor nucleus of the vagus (DMV).
      Based on a single study in cats, it is now widely accepted that these neurones
      are functionally organized into two separate populations, such that stimulation
      of the caudal and rostral DMV evokes LOS relaxation and contraction,
      respectively. Our goal was to map the functional LOS responses to chemical
      stimulation in the DMV and nucleus tractus solitarius (NTS) of ferrets, an animal
      model commonly used for conscious studies on TLOSRs, and to test whether DMV
      evoked LOS relaxation is mediated through hexamethonium-sensitive vagal
      inhibitory pathways to the LOS. We used miniaturized manometry with Dentsleeve to
      monitor LOS and oesophageal pressures in decerebrate unanaesthetized ferrets. LOS
      relaxation was evoked readily in response to gastric insufflation, which shows
      that the vago-vagal reflex was intact in this preparation. Microinjections of l
      glutamate (12.5 nmol L-1 in 25 nL) were made into the DMV from approximately -
      1.5 to + 2.0 mm relative to the obex. Microinjections into the caudal (- 1.5 to +
      0.0 mm behind obex) and intermediate (+ 0.1 to + 1.0 mm rostral to obex) DMV both
      significantly decreased LOS pressure, and complete LOS relaxation was noted in
      28/32 and 11/18 cases, respectively. LOS relaxation responses to DMV
      microinjection were highly reproducible and abolished by bilateral vagotomy or
      hexamethonium (15 mg kg-1 intravenously). A nitric oxide synthase inhibitor (l
      NAME 100 mg kg-1 intramuscularly) significantly increased the time taken to reach
      the maximal response. Increases in LOS pressure (24 +/- 4 mmHg; n = 3) were
      obtained only when stimulation sites were located equal to greater than 1.5 mm
      rostral to the obex. LOS relaxation (- 78 +/- 10%; n = 6) was evoked by
      stimulation of the NTS but not immediately outside of the NTS (11 +/- 27%; n =
      5). We conclude that there is a very extensive population of 'inhibitory' motor
      neurones in the DMV that may account for the predominant vagal-inhibitory tone in
      ferrets. As NTS stimulation evokes LOS relaxation and the predominant response to
      DMV stimulation is also LOS relaxation, this vago-vagal reflex may involve an
      excitatory interneurone between the NTS and DMV vagal inhibitory output.

PMID- 12061942
TI  - How useful are retrospective studies in evaluating therapeutic interventions?

PMID- 12061943
TI  - Amyotrophic lateral sclerosis: evaluation and treatment of respiratory
      impairment.
AB  - Patients with amyotrophic lateral sclerosis (ALS) invariably develop respiratory
      muscle weakness and most die from pulmonary complications. There are numerous
      tests available to evaluate respiratory status in ALS and it is important to
      understand their various advantages and limitations. Forced vital capacity (FVC)
      is commonly used but can remain normal despite substantial inspiratory muscle
      weakness. Maximal pressures measured at the mouth are useful for excluding
      weakness if they are normal but are difficult to interpret if abnormal. Invasive
      testing, such as measurement of transdiaphragmatic pressure, provides an accurate
      measure of inspiratory strength but is not readily available and is not practical
      for serial measures. There are supportive respiratory techniques that have been
      shown to benefit patients with ALS. Clinicians should be familiar with these
      interventions, including mechanically assisted coughing, non-invasive ventilation
      and tracheostomy with mechanical ventilation. Observational studies have
      demonstrated improved survival and quality of life with noninvasive ventilation.
      Tracheostomy with long-term mechanical ventilation is not frequently used but can
      be an important component of care for ALS. This review describes an approach to
      respiratory evaluation and care of patients with ALS.

PMID- 12061944
TI  - Prognostic modelling of therapeutic interventions in amyotrophic lateral
      sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a disease with a widely
      varying prognosis. The majority of patients survive about 3 years, but a
      significant number survive for 10 years or more, leading to problems in clinical
      trial design. OBJECTIVE: To demonstrate that simple clinical variables can be
      used to construct a robust predictive model for survival, and to assess the
      effect of a known treatment within this model. METHODS: We carried out a
      retrospective multivariate modelling of a database of 841 patients with ALS seen
      over a 10-year period in a specialist motor neuron disorders clinic. The use of
      riluzole was tested as a prognostic factor within the model. RESULTS: A
      prognostic score generated from one cohort of patients predicted survival for a
      second cohort of patients (r(2) = 0.78). Prognostic variables included site of
      onset, age of onset, time from symptom onset to diagnosis, and El Escorial
      category at presentation. Riluzole therapy was an independently significant
      prognostic factor (relative risk of death 0.48, P < 0.0001, model chi(2) 297, P <
      0.0001). CONCLUSIONS: Clinical databases can be used to generate multivariate
      prognostic models in ALS. Such models could be used to predict survival, to
      improve criteria for matching of patients in future clinical trials, and to test
      the impact of interventions.

PMID- 12061946
TI  - Changes in motor unit numbers in patients with ALS: a longitudinal study using
      the adapted multiple point stimulation method.
AB  - METHOD: The adapted multiple point stimulation (AMPS) method for calculating
      motor unit numbers (MUNE) was applied in 12 patients with amyotrophic lateral
      sclerosis (ALS) before riluzole therapy (T(0)) and again after 4, 8 and 12 months
      of treatment. RESULTS: Paired Student's t-test indicated a significant decrease
      of thenar MUNE and compound muscle action potential (CMAP) size at each 4-monthly
      interval, while average surface motor unit potential (SMUP) size did not change
      significantly over time. The rate of motor unit (MU) loss at month 4 was more
      than 20% in six patients (group 1) and less than 20% in six other patients (group
      2). Comparison of groups 1 and 2 by Mann-Whitney U-testing indicated that percent
      changes in thenar MUNE and CMAP size compared to baseline were significantly
      different at months 4, 8 and 12, while no difference between the two groups was
      found for average SMUP size variations. In the group with a slow rate of MU loss,
      CMAP size remained stable, while in the group with a rapid rate of MU loss, there
      was a dramatic reduction in size of the CMAP. A positive correlation was found
      between percent change in thenar MUNE at T(4) and at T(12) (P < 0.001).
      CONCLUSION: AMPS is a useful technique to document MUNE, SMUP size and CMAP size
      changes over time in patients with ALS.

PMID- 12061945
TI  - Long-term safety of riluzole in amyotrophic lateral sclerosis.
AB  - OBJECTIVES: This international, open-label, multicentre extension of riluzole
      pivotal studies was designed to assess the long-term safety of riluzole in the
      treatment of amyotrophic lateral sclerosis (ALS). METHOD: The studies were
      carried out at 31 different centres, 23 in Europe and eight in North America. 516
      patients with diagnosed probable or definite ALS and who had participated
      previously in one of two international multicentre randomized double-blind
      placebo-controlled, parallel-group trials, were enrolled in the extensions. 58 of
      these patients had taken part in a randomized phase II trial (placebo or riluzole
      100 mg/day) and 458 in a randomized, dose-ranging phase III trial (placebo or
      riluzole, 50, 100 or 200 mg/day). All participants in the open-label continuation
      received 100 mg/day of riluzole (50 mg b.i.d.) RESULTS: At the end of the open
      label study, the average exposure time of the patients to riluzole was 28.7 +/-
      14.4 months, with a maximum exposure time of 81 months. Most of the adverse
      events recorded reflected the progression of ALS, in particular the deterioration
      of the respiratory status of the patients. No particular adverse event, or
      frequency of adverse event, appeared to be related to the dose level of the
      previous double-blind riluzole treatment. Nor were any adverse events associated
      with the switch-over from double-blind placebo to open-label riluzole.
      CONCLUSIONS: This open-label extension study reinforces and extends the results
      of the preceding double-blind trials regarding the safety of riluzole and shows
      that the drug is well tolerated for long periods of up to almost 7 years.

PMID- 12061947
TI  - The corticomotor threshold is not dependent on disease duration in amyotrophic
      lateral sclerosis (ALS).
AB  - INTRODUCTION: It is suggested that early in ALS the corticomotor threshold (CMT)
      is low, but increases with increasing duration of the disease. POPULATION AND
      METHODS: We compared CMT, central conduction time and motor-evoked response/M
      wave amplitude in two populations of ALS patients: one with disease duration
      shorter than 6 months (Group A, 11 patients) and another who had had the disease
      for more than 24 months (Group B, 14 patients). These two groups were compared
      with a control group of 30 subjects. In all the ALS patients, abductor digiti
      minimi (ADM) strength was greater than MRC 3. RESULTS: M-wave amplitude was
      comparable in the three groups. We found no difference between the three groups
      in these transcranial magnetic stimulation studies and there was no correlation
      between disease duration time and CMT. CONCLUSION: We did not confirm a relation
      between CMT and disease duration. An increased CMT late in the disease
      progression is associated with greater lower motor neuron loss, and greater
      corticospinal tract degeneration with dispersion of the descending motor volley.

PMID- 12061948
TI  - No effect of creatine on respiratory distress in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To evaluate the effect of creatine supplementation on the respiratory
      function of patients with advanced amyotrophic lateral sclerosis (ALS). METHODS:
      Five grams creatine daily were administered orally to 14 patients with definite
      advanced ALS. For comparison we used a group of 13 patients with a similar
      respiratory function. All patients performed pulmonary function testing including
      forced vital capacity (FVC), forced expiratory volume (FEV(1)), peak expiratory
      flow rate (PEF) and maximum voluntary ventilation (MVV) -- expressed as percent
      of the predicted value -- at baseline and each month thereafter. RESULTS: There
      was no significant difference in any measured variable between the treatment
      group and the control group at 1, 2, 3 and 4 months follow-up. Thereafter the
      high patient drop-out rate did not allow statistical evaluation. CONCLUSION: The
      present study did not show any clinically significant, long-term effect of
      creatine on the function of respiratory muscles in ALS patients with respiratory
      distress.

PMID- 12061949
TI  - A unified model of spatial and episodic memory.
AB  - Medial temporal lobe structures including the hippocampus are implicated by
      separate investigations in both episodic memory and spatial function. We show
      that a single recurrent attractor network can store both the discrete memories
      that characterize episodic memory and the continuous representations that
      characterize physical space. Combining both types of representation in a single
      network is actually necessary if objects and where they are located in space must
      be stored. We thus show that episodic memory and spatial theories of medial
      temporal lobe function can be combined in a unified model.

PMID- 12061950
TI  - Partnership status and the temporal context of relationships influence human
      female preferences for sexual dimorphism in male face shape.
AB  - Secondary sexual characteristics may indicate quality of the immune system and
      therefore a preference for masculinity may confer genetic benefits to offspring;
      however, high masculinity may be associated with costs of decreased paternal
      investment. The current study examined women's preferences for masculinity in
      male faces by using computer graphics to allow transformation between feminine
      and masculine versions of individual male faces. We found that preferences for
      masculinity are increased when women either have a partner or are considering a
      short-term relationship. Such preferences are potentially adaptive, serving to:
      (i) maximize parental investment and cooperation in long-term relationships by
      biasing choices towards feminine faced males, and (ii) maximize possible good
      gene benefits of short-term or extra-pair partners by biasing choices towards
      masculine faced males. We also found that individuals using oral contraception do
      not show the above effects, indicating that such hormonal intervention
      potentially disrupts women's choices for evolutionarily relevant benefits from
      males.

PMID- 12061952
TI  - Chimpanzees and the mathematics of battle.
AB  - Recent experiments have demonstrated the importance of numerical assessment in
      animal contests. Nevertheless, few attempts have been made to model explicitly
      the relationship between the relative number of combatants on each side and the
      costs and benefits of entering a contest. One framework that may be especially
      suitable for making such explicit predictions is Lanchester's theory of combat,
      which has proved useful for understanding combat strategies in humans and several
      species of ants. We show, with data from a recent series of playback experiments,
      that a model derived from Lanchester's 'square law' predicts willingness to enter
      intergroup contests in wild chimpanzees (Pan troglodytes). Furthermore, the model
      predicts that, in contests with multiple individuals on each side, chimpanzees in
      this population should be willing to enter a contest only if they outnumber the
      opposing side by a factor of 1.5. We evaluate these results for intergroup
      encounters in chimpanzees and also discuss potential applications of Lanchester's
      square and linear laws for understanding combat strategies in other species.

PMID- 12061951
TI  - Contrast in adaptive mass gains: Eurasian golden plovers store fat before
      midwinter and protein before prebreeding flight.
AB  - Before predictable periods of high nutritional demand and little or no intake,
      vertebrates store fuel mainly composed of energy-dense lipids or energy-poor but
      protein-rich muscle tissue. Documenting contrasts in fuel composition and storage
      patterns within species, or even within individuals, would greatly help to
      elucidate the functional significance of the variety of storage strategies
      demonstrated in birds. We show here that the 40-50 g mass gain of 200 g in
      Eurasian golden plovers (Pluvialis apricaria) in autumn in The Netherlands
      consists of fat only, but that the similar gain in body mass in spring consists
      of proteinaceous tissue (pectoral and other skeletal muscle and possibly skin
      tissue). That the same golden plovers store energy in autumn and store protein in
      spring suggests that they face energy deficits in early winter and risk protein
      deficits in spring, especially perhaps after arrival on the breeding grounds in
      late April and early May. In autumn and winter their diet consists largely of
      protein-rich earthworms, but upon arrival on Low Arctic and montane tundras,
      golden plovers tend to eat berries which are rich in sugars but notably poor in
      proteins. We therefore propose that the build-up of proteinaceous tissue in
      spring reflects a strategic storage of a nutritional resource that is likely to
      be in short supply somewhat later in the year.

PMID- 12061953
TI  - Interaction between natural and sexual selection during the evolution of mate
      recognition.
AB  - The interaction between natural and sexual selection is central to many theories
      of how mate choice and reproductive isolation evolve, but their joint effect on
      the evolution of mate recognition has not, to my knowledge, been investigated in
      an evolutionary experiment. Natural and sexual selection were manipulated in
      interspecific hybrid populations of Drosophila to determine their effects on the
      evolution of a mate recognition system comprised of cuticular hydrocarbons
      (CHCs). The effect of natural selection in isolation indicated that CHCs were
      costly for males and females to produce. The effect of sexual selection in
      isolation indicated that females preferred males with a particular CHC
      composition. However, the interaction between natural and sexual selection had a
      greater effect on the evolution of the mate recognition system than either
      process in isolation. When natural and sexual selection were permitted to operate
      in combination, male CHCs became exaggerated to a greater extent than in the
      presence of sexual selection alone, and female CHCs evolved against the direction
      of natural selection. This experiment demonstrated that the interaction between
      natural and sexual selection is critical in determining the direction and
      magnitude of the evolutionary response of the mate recognition system.

PMID- 12061954
TI  - Dietary carotenoids predict plumage coloration in wild house finches.
AB  - Carotenoid pigments are a widespread source of ornamental coloration in
      vertebrates and expression of carotenoid-based colour displays has been shown to
      serve as an important criterion in female mate choice in birds and fishes. Unlike
      other integumentary pigments, carotenoids cannot be synthesized; they must be
      ingested. Carotenoid-based coloration is condition-dependent and has been shown
      to be affected by both parasites and nutritional condition. A controversial
      hypothesis is that the expression of carotenoid-based coloration in wild
      vertebrates is also affected by the amount and types of carotenoid pigments that
      are ingested. We tested this carotenoid-limitation hypothesis by sampling the gut
      contents of moulting house finches and comparing the concentration of carotenoid
      pigments in their gut contents with the colour of growing feathers. We found a
      positive association: males that ingested food with a higher concentration of
      carotenoid pigments grew brighter ornamental plumage. We also compared the
      concentration of carotenoids in the gut contents of males from two subspecies of
      house finches with small and large patches of carotenoid-based coloration.
      Consistent with the hypothesis that carotenoid access drives the evolution of
      carotenoid-based colour displays, males from the population with limited
      ornamentation had much lower concentrations of carotenoids in their gut contents
      than males from the population with extensive ornamentation. These observations
      support the idea that carotenoid intake plays a part in determining the plumage
      brightness of male house finches.

PMID- 12061955
TI  - Evolution of larger sperm in response to experimentally increased sperm
      competition in Caenorhabditis elegans.
AB  - Sperm morphology evolves rapidly, resulting in an exceptional diversity of sperm
      size and shape across animal phyla. This swift evolution has been thought to
      prevent fertilizations between closely related species. Alternatively, recent
      correlative analyses suggest that competition among sperm from more than one male
      may cause sperm diversity, but these hypotheses have not been tested. Here, we
      test experimentally the effect of sperm competition on sperm-size evolution using
      the nematode Caenorhabditis elegans. This worm has a three day generation time,
      which allowed the study to cover many generations. Sperm volume increased nearly
      20% over 60 generations in lines genetically induced to have high levels of sperm
      competition compared with those of control lines. These results show that sperm
      competition can and does cause morphological evolution of sperm and, therefore,
      can explain much of the diversity in sperm morphology.

PMID- 12061956
TI  - Age-specific survival and reproductive probabilities: evidence for senescence in
      male fallow deer (Dama dama).
AB  - Survival and reproduction are key features in the evolution of life-history
      strategies. In this study, we use capture-mark-resighting and multi-state models
      to examine survival senescence and reproductive senescence in six successive
      cohorts of fallow bucks that were studied for 16 years. We found that the overall
      age-specific survival probabilities of males were highly variable and the best
      fitting model revealed that fallow bucks have four life-history stages: yearling,
      pre-reproductive, prime-age and senescent. Pre-reproductive males (2 and 3 years
      old) had the highest survival. Survival declined sharply after the age of 9
      years, indicating that senescence had begun. When we considered reproducing and
      non-reproducing males separately, there was no evidence of senescence in the
      former, and steadily decreasing survival after the onset of social maturity in
      the latter. Reproduction probability also declined in older males, and thus we
      provide very strong evidence of senescence. Reproducers had a greater chance of
      reproducing again in the following year than non-reproducers. Furthermore, there
      were differences in the survival probabilities, with reproducers consistently
      surviving better than non-reproducers. In our study population, reproducers
      allocate more to the effort to reproduce than non-reproducers. Therefore our
      results indicate the generally higher phenotypic quality of reproducing males.
      These results, along with earlier studies on the same population, could indicate
      positive relationships between fitness correlates.

PMID- 12061957
TI  - Canal construction destroys the barrier between major European invasion lineages
      of the zebra mussel.
AB  - Since the mid-1980s the zebra mussel, Dreissena polymorpha, Pallas 1771, has
      become the protagonist of a spectacular freshwater invasion in North America due
      to its large economic and biological impact. Several genetic studies on American
      populations have failed to detect any large-scale geographical patterns. In
      western Europe, where D. polymorpha has been a classical invader from the
      Pontocaspian since the early 19th century, the situation is strikingly different.
      Here, we show with genetic markers that two major western European invasion
      lineages with lowered genetic variability within and among populations can be
      discriminated. These two invasion lineages correspond with two separate navigable
      waterways to western Europe. We found a rapid and asymmetrical genetic
      interchange of the two invasion lines after the construction of the Main-Danube
      canal in 1992, which interconnected the two waterways across the main watershed.

PMID- 12061958
TI  - Were the first springtails semi-aquatic? A phylogenetic approach by means of 28S
      rDNA and optimization alignment.
AB  - Emergence from an aquatic environment to the land is one of the major
      evolutionary transitions within the arthropods. It is often considered that the
      first hexapods, and in particular the first springtails, were semi-aquatic and
      this assumption drives evolutionary models towards particular conclusions. To
      address the question of the ecological origin of the springtails, phylogenetic
      analyses by optimization alignment were performed on D1 and D2 regions of the 28S
      rDNA for 55 collembolan exemplars and eight outgroups. Relationships among the
      orders Symphypleona, Entomobryomorpha and Poduromorpha are inferred. More
      specifically, a robust hypothesis is provided for the subfamilial relationships
      within the order Poduromorpha. Contrary to previous statements, the semi-aquatic
      species Podura aquatica is not basal or 'primitive', but well nested in the
      Poduromorpha. The analyses performed for the 24 different weighting schemes
      yielded the same conclusion: semi-aquatic ecology is not ancestral for the
      springtails. It is a derived condition that evolved independently several times.
      The adaptation for semi-aquatic life is better interpreted as a step towards
      independence from land, rather than indication of an aquatic origin.

PMID- 12061959
TI  - Inbreeding and experience affect response to climate change by endangered
      woodpeckers.
AB  - In recent decades, female red-cockaded woodpeckers (Picoides borealis) have laid
      eggs increasingly earlier in response to a changing climate, as has been observed
      in several other bird species breeding at north temperate latitudes. Within each
      year, females that lay earlier are more productive than females that lay later.
      However, inexperienced females, experienced females who change mates and inbred
      birds have not adjusted to the changing climate by laying earlier, and have
      suffered reproductive costs as a result. Failure to respond to global climate
      change may be a further example of the reduced ability of inbred animals to
      respond to environmental challenges.

PMID- 12061960
TI  - Timing of transmission and the evolution of virulence of an insect virus.
AB  - We used the nuclear polyhedrosis virus of the gypsy moth, Lymantria dispar, to
      investigate whether the timing of transmission influences the evolution of
      virulence. In theory, early transmission should favour rapid replication and
      increase virulence, while late transmission should favour slower replication and
      reduce virulence. We tested this prediction by subjecting one set of 10 virus
      lineages to early transmission (Early viruses) and another set to late
      transmission (Late viruses). Each lineage of virus underwent nine cycles of
      transmission. Virulence assays on these lineages indicated that viruses
      transmitted early were significantly more lethal than those transmitted late.
      Increased exploitation of the host appears to come at a cost, however. While
      Early viruses initially produced more progeny, Late viruses were ultimately more
      productive over the entire duration of the infection. These results illustrate
      fitness trade-offs associated with the evolution of virulence and indicate that
      milder viruses can obtain a numerical advantage when mild and harmful strains
      tend to infect separate hosts.

PMID- 12061962
TI  - Sensitive dependencies and separation distances for genetically modified
      herbicide-tolerant crops.
AB  - The amount of land available for the coexistent growing of both organic and
      genetically modified herbicide-tolerant (GMHT) crops depends on the separation
      distance between the two types of crop. The form of the decline in the proportion
      of land available for growing one of these crop types due to increasing
      separation distance is linear on a suitable scale, but with a slope and intercept
      that are sensitively dependent on the proportion of the other crop already
      present. Spatially explicit simulations from realistic scenarios indicate that a
      major increase in separation distances, currently under review by the UK
      government, may have serious implications for the future coexistence of organic
      and GMHT crops in the UK.

PMID- 12061961
TI  - Epistasis and hybrid sterility in Saccharomyces.
AB  - Hybrid sterility is thought to be due to deleterious epistatic interactions
      between genes from different species. Here we demonstrate that dominant genic
      incompatibility does not contribute to sterility in hybrids between Saccharomyces
      cerevisiae and five closely related species. Sterile diploids were made fertile
      by genome doubling to produce hybrid tetraploids. Based on these and previous
      results, we conclude that neither genic incompatibility nor classical chromosomal
      speciation models apply.

PMID- 12061963
TI  - The evolution of self-fertilization in density-regulated populations.
AB  - The evolution of selfing in hermaphrodites has been studied to reveal the
      demographic conditions that lead to intermediate selfing rates. Using a
      demographic model based on Ricker-type density regulation, we assume first that,
      independent of population density, inbred individuals survive less well than
      outbred individuals and second, that inbred and outbred individuals differ in
      their competitive abilities in density-regulated populations. The evolution of
      selfing, driven by inbreeding depression and the cost of outcrossing, is then
      analysed for three fundamentally different demographic scenarios: stable
      population densities, deterministically varying population densities (resulting
      from cyclical or chaotic population dynamics) and stochastic fluctuations of
      carrying capacities (resulting from environmental noise). We show that even under
      stable demographic conditions evolutionary outcomes are not confined to either
      complete selfing or full outcrossing. Instead, intermediate selfing rates arise
      under a wide range of conditions, depending on the nature of competitive
      interactions between inbred and outbred individuals. We also explore the
      evolution of selfing under deterministic and stochastic density fluctuations to
      demonstrate that such environmental conditions can evolutionarily stabilize
      intermediate selfing rates. This is the first study, to our knowledge, to
      consider in detail the effect of density regulation on the evolution of selfing
      rates.

PMID- 12061964
TI  - When looks can kill: the evolution of sexually dimorphic floral display and the
      extinction of dioecious plants.
AB  - Dioecious plants (with separate male and female individuals) more often have
      drab, inconspicuous flowers than related bisexual plants. Models indicate,
      however, that similar conditions favour the evolution of showy floral displays in
      dioecious and bisexual plants. One difference, however, is that dioecious plants
      may evolve floral displays that are sexually dimorphic. We show that males are
      more likely to evolve showy flowers than females in animal-pollinated plants,
      especially when pollinators are abundant. We demonstrate that this dimorphism
      places showy dioecious plants at a much higher risk of extinction during years of
      low pollinator abundance because pollinators may fail to visit female flowers.
      The higher extinction risk of showy dioecious plants provides an explanation for
      the fact that dioecious plants that do persist tend to have inconspicuous flowers
      and are more often wind pollinated. It may also help explain why dioecious plants
      are less species-rich than related bisexual plants.

PMID- 12061966
TI  - The contribution of apparent and inherent usability to a user's satisfaction in a
      searching and browsing task on the Web.
AB  - Previous research found that apparent and inherent usability had big influences
      on user's acceptance of computer systems. This research extended these findings
      to the area of user's satisfaction. The study investigated the impact of inherent
      and apparent usability on user's satisfaction of Web page designs while the two
      main tasks on the World Wide Web, searching and browsing, were performed. The
      results indicated that inherent usability was the main factor contributing to
      user's satisfaction in both searching and browsing. General principles and
      specific recommendations for the design and evaluation of Web page designs are
      derived from these findings.

PMID- 12061965
TI  - Spinal loading when lifting from industrial storage bins.
AB  - The study documented three-dimensional spinal loading during lifting from an
      industrial bin. Two lifting styles and two bin design factors were examined in
      Phase I. The lifting style measures in Phase I were one hand versus two hand and
      standing on one foot versus two feet. The bin design variables were region of
      load in the bin and bin height. The Phase II study examined one-handed lifting
      styles with and without supporting body weight with the free hand on the bin as
      well as region and the number of feet. Twelve male and 12 female subjects lifted
      an 11.3 kg box from the bin. Spinal compression, lateral shear and anterior -
      posterior shear forces were estimated using a validated EMG-assisted
      biomechanical model. Phase I results indicated that the bin design factor of
      region had the greatest impact on spinal loading. The upper front region
      minimized spinal loading for all lifting styles. Furthermore, the lifting style
      of two hands and two feet minimized spinal loading. However, comparing Phase I
      two-handed lifting with Phase II one-handed supported lifting, the one-handed
      supported lifting techniques had lower compressive and anterior - posterior shear
      loads in the lower regions as well as the upper back region of the bin. A bin
      design that facilitates lifting from the upper front region of the bin reduces
      spinal loading more effectively than specific lifting styles. Furthermore, a bin
      design with a hand hold may facilitate workers using a supported lifting style
      that reduces spinal loading.

PMID- 12061967
TI  - Inter-digit co-ordination and object-digit interaction when holding an object
      with five digits.
AB  - The current study investigated inter-digit co-ordination and object-digit
      interaction during sustained object holding tasks by using five, six-component
      force/torque sensors. The sum of the individual finger normal forces and the
      thumb normal force showed a parallel variation with a mean median correlation
      coefficient of 0.941. The normal force traces demonstrated the lowest coefficient
      of variation (about 9% as averaged across digits) as compared with other
      force/torque traces. The sum for the variances of the normal forces of the index,
      middle, ring, and little fingers was about 50% of the variance of the summed
      normal force of the four fingers. Of the five digits, the thumb, index, middle,
      ring and little fingers accounted for 50.0, 15.4, 14.6, 11.7 and 7.3% of the
      total normal force; and 39.4, 9.9, 19.3, 14.0 and 17.5% of the total vertical
      shear force (i.e. the load), respectively. The ratios of the normal force to the
      resultant shear force were 2.6, 4.5, 1.8, 2.2 and 1.3 for the thumb, index,
      middle, ring and little finger, respectively. The centre of pressure migration
      area of a single digit at the object-digit surface during object holding ranged
      from 0.30 to 1.21 mm(2). The current study reveals a number of detailed object
      digit mechanics and multiple digits co-ordination principle. The results of this
      study may help to improve ergonomic designs that involve the usage of multiple
      digits.

PMID- 12061968
TI  - Impact of observers' experience and training on reliability of observations for a
      manual handling task.
AB  - Observation reliability (agreement percentage and kappa coefficients) for six
      experienced ergonomists and six untrained participants was computed. Participants
      were first tested after a training session and 1 week later after an additional
      practice session. Two formats were used: free practice and directed exercise.
      Reliability was tested for 17 variables and 20 sequences using photographic and
      video supports. The participants were asked to indicate whether they were
      confident about their answer, to rate this confidence on a scale of 1 to 10, and
      when the confidence rating was below 8, to provide a reason for this. Experience
      and additional practices had no clear impact on reliability, which was excellent
      overall. The main reason given was that the event to be observed took place at
      the borderline between two classes. The observers' rating on the scale appeared
      to be tied to the subsequent reliability computed. The use of a confidence scale
      appeared to be a useful tool for forecasting observation problems.

PMID- 12061969
TI  - Significance of house painters' work techniques on shoulder muscle strain during
      overhead work.
AB  - House painters represent a group of construction workers with a high frequency of
      neck and shoulder complaints and concomitant high risks for early retirements.
      Shoulder tendinitis, especially supraspinatus tendinitis, occurs frequently among
      house painters. The tasks of sanding and painting of ceilings with extension
      handles are particularly strenuous for these body regions. The purpose of this
      study was to identify work techniques that would be less strenuous to the arms
      and shoulders during sanding work. A biomechanical model was applied to quantify
      the shoulder loads during sanding and to determine the likely muscle force
      distribution. The necessary input data were measured experimentally for the model
      by means of a load cell and strain gauges on an extension handle, a Kistler force
      plate, and a MacReflex motion analysis system. Forty experienced male painters
      participated in the study. Three different work techniques were identified: the
      normal technique, the reversed grip and the pushing technique. The pushing
      technique was characterized by shorter stroke length and lower speed of the
      grinding block than the other techniques. The painters among the group of
      subjects who used the pushing technique were found to report fewer shoulder
      disorders during sanding than the others. The most common shoulder tendinitis is
      the supraspinatus tendinitis, also among house painters, and using the Pushing
      technique could possibly prevent from this disorder. However, further research in
      larger groups of house painters is needed to be able to recommend this technique
      for a wider use.

PMID- 12061970
TI  - A randomized comparison of chloroquine, amodiaquine and their combination with
      pyrimethamine-sulfadoxine in the treatment of acute, uncomplicated, Plasmodium
      falciparum malaria in children.
AB  - The increasing resistance of Plasmodium falciparum to antimalarial monotherapy
      (MT) has created an urgent need for the evaluation of alternative effective,
      safe, cheap, readily available and affordable, combination treatments (CT) with
      antimalarial drugs. In the present study, the efficacies of chloroquine (CQ) or
      amodiaquine (AQ) in the oral treatment of acute, symptomatic, uncomplicated,
      Plasmodium falciparum malaria were compared with those of oral treatments with
      the combination of CQ or AQ with pyrimethamine-sulfadoxine (PS). The CQ and AQ
      were each given at a dose of 10 mg/kg.day for 3 days (days 0, 1 and 2), with or
      without PS given as a single dose (25 mg sulfadoxine/kg) at presentation (day 0).
      Overall, 303 children aged 0.5-10 years (74 given CQ, 82 AQ, 72 CQPS and 75 AQPS)
      were evaluated. The fever-clearance time (FCT) was significantly shorter in those
      treated with AQPS than in those treated with CQ or CQPS. The proportions of
      patients with complete clearance of their parasitaemias on days 1 and 2 were
      significantly larger and the parasite-clearance times (PCT) were all
      significantly shorter with the drug combinations than with their corresponding
      MT. For example, the mean (S.D.) PCT were 2.6 (0.8) days for CQ v. 2.1 (0.8) days
      for CQPS (P=0.0002), and 2.6 (0.7) days for AQ v. 2.1 (0.7) days for AQPS
      (P=0.00001). The cure 'rates' on days 14, 21 and 28 were also significantly
      higher with AQ, CQPS and AQPS than with CQ; those on day 28, for example, were
      47.2%, 98.7%, 100% and 100% for CQ, AQ, CQPS and AQPS, respectively (P=0.000001).
      Gametocyte carriages on day 3 or on days 3, 7 and/or 14 combined were
      significantly lower in those treated with CQPS than in those given CQ; there was
      no gametocyte carriage in the CT groups on day 28. In the CQ group, eight of 13
      children with gametocytaemia on day 3 had a response indicative of resistance.
      However, the five CQ-resistant infections that were re-treated with AQPS
      responded promptly, with a PCT significantly shorter than that during the initial
      treatment with CQ and with a cure 'rate' of 100% on day 28. Adverse reactions to
      treatment were similar on the first and subsequent days of treatment and were
      tolerable except for pruritus, which was significantly more common in children
      treated with CQ alone than in the other treatment groups. Haematological and
      biochemical parameters were not adversely affected by any treatment. The CQPS and
      AQPS combinations appear to be well tolerated and may be useful as alternatives
      to monotherapy with CQ or AQ as resistance to the single drugs develops.

PMID- 12061971
TI  - Efficacy of chloroquine in the treatment of uncomplicated, Plasmodium falciparum
      malaria in northern Ghana.
AB  - Chloroquine (CQ) resistance in Plasmodium falciparum contributes to growing
      malaria-attributable morbidity and mortality in sub-Saharan Africa. However, the
      extent and degree of such resistance vary considerably between endemic areas.
      Data on CQ resistance in northern Ghana are almost entirely lacking. The
      therapeutic efficacy of CQ in uncomplicated malaria was therefore assessed, in a
      standard, 14-day protocol, in 225 children aged <5 years in Tamale, in the
      Northern region of Ghana. Early treatment failure (ETF) was observed in 11% of
      the children and late treatment failure in 18%. High initial parasite density and
      young age were independent predictors for ETF. Resistant parasitological
      responses (RI-RIII) were seen in 57% of the cases that could be classified. More
      than half of these responses occurred in children fulfilling the criteria for
      adequate clinical response (ACR), indicating a considerable lack of agreement
      between parasitological and clinical outcome. During the follow-up period,
      haemoglobin levels increased by approximately 1g/dl not only in patients with ACR
      but also in those who experienced clinical failure more than 1 week post
      treatment. As CQ-treatment failure occurred in >25% of the children and more than
      half of the parasitological responses indicated resistance, current
      recommendations for the treatment of uncomplicated malaria in young children in
      northern Ghana have to be reconsidered.

PMID- 12061972
TI  - The restoring effect of trifluralin and benznidazole on the abnormal fatty-acid
      pattern induced by Trypanosoma cruzi in the liver microsomes of infected mice.
AB  - The fatty-acid composition of liver lipids from mice infected with Trypanosoma
      cruzi (clone H510C8C3) or uninfected mice was investigated. The infected animals
      were treated orally for 30 days, with trifluralin (TFL) or benznidazole (BNZ),
      each at 100mg/kg.day, or only with the peanut oil used as the drug vehicle. The
      uninfected mice were also given the peanut oil. The treatments were stopped 10
      days before the animals were killed. The liver microsomal lipids of each mouse
      were isolated and then analysed by gas-liquid chromatography. In terms of the
      total lipids, untreated infection evoked a significant increase in saturated
      fatty acids and the members of the n-9 fatty-acid family, with a concomitant
      decrease in the polyenoates of the n-3 and n-6 fatty-acid series. Each lipid
      subclass was affected to a different extent, the phospholipids being affected
      most. All lipid fractions, apart from the cholesterol esters, showed a
      significant increase in the proportion of n-9 isomers. Infection also produced a
      marked increase in the absolute amounts of triacylglycerides, cholesterol and
      cholesterol esters in liver microsomal membranes. After BNZ or TFL treatment, the
      fatty-acid pattern of mice that had been infected was indistinguishable from that
      of the control mice. The possible role of desaturase activity in the alterations
      observed is discussed.

PMID- 12061973
TI  - Towards a standard battery of microsatellite markers for the analysis of the
      Leishmania donovani complex.
AB  - The investigation of microsatellite markers has recently superseded that of
      isoenzymes for many population-biology applications. Microsatellites have the
      advantages of being dominant, neutral, highly polymorphic and easily scored by
      high-throughput methods. However, it is necessary to develop a new panel of
      markers for each group of organisms of interest. Previously, only about 5% of the
      markers that amplify Leishmania major microsatellite loci were also found to
      amplify L. donovani loci. A panel of 20 microsatellite markers that are
      polymorphic in L. donovani and L. infantum has now been developed, using a rapid
      enrichment method that will be suitable for developing libraries of markers for
      other trypanosomatid species. This is the first panel of polymorphic
      microsatellite markers, to be isolated de novo from any species of Leishmania,
      that is large enough for population-biology applications.

PMID- 12061974
TI  - Identification and characterization of a 26- to 28-kDa circulating antigen of
      Fasciola gigantica.
AB  - As a disease of domestic ruminants, fascioliasis is of considerable economic
      importance. Although serological tests are available for the diagnosis of the
      disease, they are of generally low specificity because of cross-reactivity with
      antigens from other parasites. There is a need to identify other Fasciola
      antigens on which more specific tests could be based. In the present study, a
      specific rabbit anti-serum and western-blot analyses were used to demonstrate the
      presence of a highly reactive antigen of 26-28 kDa not only in an extract of
      adult F. gigantica but also in the excretory/secretory products of the worms and
      in the bile secretions and sera of cattle that were naturally infected with this
      parasite. The 26- to 28-kDa antigen was isolated from preparative polyacrylamide
      gels, by electro-elution. The purified antigen showed a single peak at 5.8 min
      when analysed by capillary zone electrophoresis. It was characterized as protein
      containing 47.5% hydrophilic and 29.3% hydrophobic amino acids. Immunostaining
      demonstrated that the target epitope was located in the gut and tegument of adult
      F. gigantica and within the bile ducts, the portal tracts of the livers and the
      mucosa and muscularis of the gallbladders of infected cattle. A simple and rapid
      dot-ELISA technique based on the specific rabbit anti-serum was 100% specific
      when tested on the sera from nine cattle infected with F. gigantea and 27
      uninfected cattle. In conclusion, the 26- to 28-kDa Fasciola antigen may be a
      promising candidate for the immunodiagnosis of fascioliasis.

PMID- 12061975
TI  - Onchocerciasis: the clinical and epidemiological burden of skin disease in
      Africa.
AB  - An attempt was made to assess the true public-health importance of onchocercal
      skin disease throughout the African region and hence provide an objective basis
      for the rational planning of onchocerciasis control in the area. The seven
      collaborative centres that participated in the study (three in Nigeria and one
      each in Ghana, Cameroon, Tanzania and Uganda) were all in areas of rainforest or
      savannah-forest mosaic where onchocercal blindness is not common. A cross
      sectional dermatological survey was undertaken at each site following a standard
      protocol. At each site, the aim was to examine at least 750 individuals aged 5
      years and living in highly endemic communities and 220-250 individuals aged 5
      years and living in a hypo-endemic (control) community. Overall, there were 5459
      and 1451 subjects from hyper-and hypo-endemic communities, respectively. In the
      highly endemic communities, the prevalence of itching increased with age until 20
      years and then plateaued, affecting 42% of the population aged 20 years. There
      was a strong correlation between the prevalence of itching and the level of
      endemicity (as measured by the prevalence of nodules; r=0.75; P<0.001). The
      results of a multivariate logistic regression analysis showed that, at the
      individual level, the presence of onchocercal reactive skin lesions (acute
      papular onchodermatitis, chronic papular onchodermatitis and/or lichenified
      onchodermatitis) was the most important risk factor for pruritus, with an odds
      ratio (OR) of 18.3 and 95% confidence interval (CI) of 15.19-22.04, followed by
      the presence of palpable onchocercal nodules (OR=4.63; CI=4.05-5.29). In
      contrast, non-onchocercal skin disease contributed very little to pruritus in the
      study communities (OR=1.29; CI=1.1-1.51). Onchocercal skin lesions affected 28%
      of the population in the endemic villages. The commonest type was chronic papular
      onchodermatitis (13%), followed by depigmentation (10%) and acute papular
      onchodermatitis (7%). The highest correlation with endemicity was seen for the
      prevalence of any onchocercal skin lesion and/or pruritus combined (r=0.8;
      P<0.001). Cutaneous onchocerciasis was found to be a common problem in many
      endemic areas in Africa which do not have high levels of onchocercal blindness.
      These findings, together with recent observations that onchocercal skin disease
      can have major, adverse, psycho-social and socio-economic effects, justify the
      inclusion of regions with onchocercal skin disease in control programmes based on
      ivermectin distribution. On the basis of these findings, the World Health
      Organization launched a control programme for onchocerciasis, the African
      Programme for Onchocerciasis Control (APOC), that covers 17 endemic countries in
      Africa.

PMID- 12061976
TI  - The effect of 5 years of annual treatment with ivermectin (Mectizan) on the
      prevalence and morbidity of onchocerciasis in the village of Gami in the Central
      African Republic.
AB  - To assess the impact of 5 years of annual community treatment with ivermectin
      (Mectizan) on the prevalence of onchocerciasis and onchocerciasis-associated
      morbidity, data collected, before and after such treatment, in the village of
      Gami, in a hyper-endemic area of the Central African Republic, were analysed.
      Skin snips from all the villagers treated in 1990 and/or 1995 were used to assess
      the prevalence and intensity of infection with Onchocerca volvulus. Ocular and
      dermatological morbidity was assessed by ophthalmological and clinical
      examinations of the same subjects. Following the five annual treatments, there
      was a reduction in the prevalence of infection and a dramatic decrease in the
      microfilarial load of the community. The prevalences of pruritus, onchocercal
      nodules and impaired vision were all significantly reduced. The results emphasise
      the long-term benefits of the mass-treatment programmes, particularly for
      children aged <10 years.

PMID- 12061977
TI  - Dracunculus medinensis and Schistosoma mansoni contain opiate alkaloids.
AB  - The results of analysis, by high-performance liquid chromatography coupled with
      electrochemical detection and by nano-electrospray-ionization, double
      quadrupole/orthogonal-acceleration, time-of-flight mass spectrometry, indicate
      that adult Dracunculus medinensis and Schistosoma mansoni both contain the opiate
      alkaloid morphine and that D. medinesis also contains the active metabolite of
      morphine, morphine 6-glucuronide. From these and previous observations, it would
      appear that many helminths are probably using opiate alkaloids as potent
      immunosuppressive and antinociceptive signal molecules, to down-regulate
      immunosurveillance responsiveness and pain signalling in their hosts.

PMID- 12061978
TI  - The multiplex-PCR-based detection and genotyping of diarrhoeagenic Escherichia
      coli in diarrhoeal stools.
AB  - In several hospitals in Beirut, Lebanon, 77 isolates of Escherichia coli were
      successfully derived from the stools of patients with diarrhoeal diseases, by
      culture on MacConkey or MacConkey-sorbitol agar. When the isolates were screened,
      using a multiplex PCR, 14 (from 14 different patients) were each found positive
      for one of the various genes defining the enterotoxigenic (five), enteroinvasive
      (four), enteroaggregative (three) or enteropathogenic (two) groups. Genotyping of
      these 14 diarrhoeagenic isolates, by pulsed-field gel electrophoresis, indicated
      that all were genomically distinct with the exception of two of the
      enteroaggregative isolates (which were of the same genotype). The E. coli
      apparently involved in diarrhoeal disease in Beirut therefore belong to at least
      four different diarrhoeagenic groups and show strain variation within each group.
      Diarrhoea in the absence of diarrhoeagenic E. coli may be the result of infection
      with bacteria other than E. coli or viral or parasitic enteropathogens.

PMID- 12061979
TI  - Toxicology of a potential molluscicide derived from the plant Solanum
      xanthocarpum: a preliminary study.
AB  - A potential molluscicidal extract, obtained from the indigenous Chinese plant
      Solanum xanthocarpum (Schrad. and Wendl), was tested for toxicity against snails
      and fish in static, acute-toxicity tests. The extract had a significant effect on
      mature and young snails of the amphibious Asian freshwater prosobranch
      Oncomelania hupensis (Gredler) and also on mature specimens of the freshwater
      pulmonate snails Biomphalaria glabrata (Say) and Lymnaea stagnalis (Linnaeus).
      The minimum dose that produced 100% mortality of snails exposed for 48h,
      4.321mg/litre, is much less than the threshold, of 100mg/litre, set for a
      potential molluscicide by the World Health Organization. In contrast, the minimum
      concentration producing 100% mortality in the fish Gobiocypris rarus (Ye and Fu)
      was 17.28mg/litre. The extract also limited the extent of water-leaving by snails
      exposed to it, an important feature for the control of amphibious snails. This
      extract thus represents a promising plant-derived molluscicide which is worthy of
      further investigation.

PMID- 12061980
TI  - Field evaluation of the ICT Malaria P.f./P.v. immunochromatographic test in
      India.

PMID- 12061981
TI  - [Doctors in training: a stimulus for society].

PMID- 12061982
TI  - [Medical care of patients with heart failure: clinical characteristics,
      determinants of prognosis and follow-up in primary care].
AB  - OBJECTIVE: To assess the process of care and prognosis of patients with heart
      failure (HF) attended in a tertiary hospital and follow up at the primary care
      level. DESIGN: Prospective study of 18 months of follow up.Setting. Tertiary
      hospital and primary care centers of the reference area. Participants. Patients
      admitted to a tertiary hospital from the first of july until de 31 of december of
      1998. OUTCOME MEASUREMENTS: Pharmacological data and morbimortality at discharge
      and at the end of the follow-up, functional capacity of survivors. RESULTS: 265
      patients were included, with a mean age of 75 years, 57% were females, 73.8% had
      HF as first diagnosis, 6.1% had MI, and 20% were attended for other medical
      reasons. The most frequent cause of HF was HTA. Drugs more prescribed at the
      discharge and follow up were diuretics and ACE inhibitors. Hospital mortality was
      6.4% and mortality at the end of the follow-up was 46% (in 77% of those for
      cardiac reasons). After being discharged 38.5% of the patients were readmitted to
      the hospital with the diagnosis of HF, 72% were visited by the family physician,
      43% at the outpatient clinic and 33% by the cardiologist; 60% of the patients who
      survived were in I-II NYHA functional class, 76% walked regularly, and 25% did
      recreational activities and physical exercise. CONCLUSIONS: Patients attended at
      the hospital with HF are an old population, have frequently associated other
      chronic diseases, and have a very bad prognosis. These patients spend an
      important amount of health resources. Drug prescription at the follow up is
      suboptimum. Patients who survived have an acceptable functional capacity.

PMID- 12061984
TI  - [Assessment of drug treatment for hypertension in a health centre as a function
      of associated chronic pathologies and degree of control of the hypertension].
AB  - OBJECTIVE: To assess the suitability of whatever hypertension medication is
      prescribed for the associated pathology in each patient, and to analyse the
      monitoring of blood pressure figures. DESIGN: A cross-sectional descriptive
      study.Setting. Urban health centre. PATIENTS: The target population were the
      hypertension patients being treated with medication and monitored at the health
      centre. Stratified random sampling by quotas of the total number with
      hypertension was performed. The sample numbered 219 patients. MEASUREMENTS: The
      clinical history of each patient selected was reviewed. To evaluate the
      hypertension treatment, we established three levels of suitability with regard to
      the accompanying pathology of each patient (suitable, intermediate, unsuitable),
      using the 1999 Hypertension Protocol of the Spanish Society of Family and
      Community Medicine. RESULTS: Out of 219 cases, treatment was suitable in 71
      (32.4%), intermediate in 91 (41.6%), and unsuitable in 57 (26%). The most
      frequently indicated drug group was the angiotensin converting enzyme inhibitor
      (ACEI) group and, jointly, ACEI and diuretics. Regarding the monitoring of blood
      pressure: 66.5% had very good monitoring, 23.2% partial and 9% poor. CONCLUSIONS:
      Most treatments are at an intermediate level of suitability: without beneficial
      or undesirable effects on the associated pathology. This makes us think we need
      to optimize the drug indicators for hypertension.

PMID- 12061985
TI  - [Suicide attempts attended at a health centre].
AB  - OBJECTIVE: To describe the characteristics of the suicide attempts attended in a
      health district over 10 years (June 1989 to December 1998). DESIGN: Cross
      sectional, descriptive study. SETTING: Primary care, rural health
      district.Patients. Everyone attended after a suicide attempt (55 cases). MAIN
      MEASUREMENTS AND RESULTS: Data of the following variables were obtained from the
      legal reports: sex, age, place of residence, prognosis, means used and year of
      attempt. 51% were women and 49% men. Average age was 34.07, SD 3.82. 96% occurred
      in the health district. 38% had light prognosis, 49% serious, 7% very serious and
      4% uncertain. The means used was ingestion of drugs in 44% of cases. 72% of the
      attempts occurred in the last 5 years. CONCLUSIONS: There were no differences
      between the sexes. Most of the patients were under 35. Drug overdose was the
      method of choice. Suicide attempts are on the up. Primary care authorities and
      doctors need to become more conscious of potentially suicidal conduct.

PMID- 12061986
TI  - [Prevalence of Helicobacter pylori infection in primary care: sero
      epidemiological study].
AB  - OBJECTIVES: To find the prevalence of Helicobacter pylori (HP) infection in
      primary care in our area and to study factors associated with this infection.
      DESIGN: Descriptive and prospective study.Setting. Urban health district with 30
      765 people registered. PARTICIPANTS: 267 patients, selected by quota sampling
      from the census of age and sex groups, as a function of an alpha of 0.05, 0.06
      accuracy, and expected prevalence of 50%. MAIN MEASUREMENTS: HP infection was
      studied through validated IgG serology (ELISA Wampole(R)). The following were
      studied as associated factors: age, sex, education, profession, alcohol and
      tobacco consumption, and non-steroidal anti-inflammatory drugs taken. RESULTS:
      Mean age was 38.4, and 51.3% were women. Prevalence of HP infection was 52.4%
      (95% CI, 46.4-58.4). This proportion increased steadily with age, with a minimum
      of 11.5% in the 0-9 years-old range and a maximum of 87.5% in the 60-69 years-old
      group. There was more HP in men (56.9%) than in women (48.2%). In univariate
      analysis a linear tendency was found between HP infection and increased age
      (P<.0001) and the consumption of alcohol (P=.003), with no relationship to other
      variables studied. In the multivariate analysis, only age maintained statistical
      significance (P=.001). CONCLUSIONS: In our area the prevalence of HP infection is
      similar to that in other studies: it increases steadily with age and shows en
      epidemiological pattern that is half-way between countries of high and low
      prevalence.

PMID- 12061987
TI  - [Bio-psychosocial treatment approach to somatizing patients in primary care: a
      pilot study].
AB  - OBJECTIVE: To explore the feasibility of a brief psychosocial intervention for
      somatizing patients in the Primary Care setting and its potential effects on
      these patients' quality of life. DESIGN: Prospective series of 12 cases, with pre
      and post-intervention analyses.Setting. Three general practices of the Basque
      Health Service. PATIENTS: Consecutive sample of 12 patients, between 18 and 65
      years-old, complaining about at least six medically unexplained symptoms for
      female patients or at least four for male patients. Intervention and measurement.
      DEPENAS intervention was carried out: Detection- Explanation-Plan-Exploration-
      Normalization-Action-Follow-up. Differences between before- and after
      intervention health-related quality of life (SF-36) were compared and group
      interviews were held with the three collaborator general practitioners. RESULTS:
      Overall quality of life improvement was estimated in 8 points (SD, 13.4; P
      =.073). Intra-GP correlation coefficients, necessary for estimate the size of the
      clinical trial, were null for five scales, and 0.058, 0.098 and 0.28 for the
      other three scales. Group interviews showed that DEPENAS bio-psycho-social
      intervention is acceptable for general practitioners and that there was a high
      risk of contamination when the same doctor simultaneously treated some patients
      and not others. CONCLUSIONS: The improvement seen after the intervention,
      although not totally attributable to it due to the lack of a control group,
      justify the need of conducting a clinical controlled trial randomised by GPs to
      avoid contamination.

PMID- 12061988
TI  - [A reflection on fibromyalgia].

PMID- 12061989
TI  - [The latest in headache treatment].

PMID- 12061990
TI  - [Immunisation: Leaps into the future. Vaccine studies at the start of the 21st
      century (I)].

PMID- 12061991
TI  - [Effectiveness of a personalized information system on the quality of family
      doctors' medical prescription].
AB  - OBJECTIVES: To evaluate the effectiveness of a system of personalised
      prescription information (PPI) to improve prescription habits of family doctors
      (FD); to examine how useful PPI is in maintaining these habits, and to analyse
      its influence through factors of the doctor and his/her environment. DESIGN:
      Cross-sectional, descriptive pilot study to analyse conditioning factors and
      possible confusion; quasi-experimental intervention study to assess the
      effectiveness of PPI, with two groups (experimental and control) and 4
      determinations (before the PPI and after: short, medium and long-term).Setting.
      Family doctors in the Murcia Region. SUBJECTS OF STUDY: The prescriptions of all
      family doctors in the Murcia region which started before PPI and which continued
      until the end of the study and without absences of over 10% at each
      measurement.Intervention. The family doctors from the Murcia city area formed the
      experimental group: they received PPI with specific proposals for improvement.
      The FDs of Cartagena and Lorca, who did not receive PPI, made up the control
      group. Statistical analysis. Logistical regression to identify conditioning
      factors. Z comparison of proportions contrasted with one-tail hypothesis to check
      the effectiveness of PPI. LIMITATIONS OF THE DESIGN: Non-randomised allocation to
      groups made comparison difficult: conditioning factors for stratification or
      adjustment were studied. PRACTICAL APPLICATION: Confirmation of PPI s
      effectiveness justifies its dissemination. If there is no such confirmation, it
      will have to be perfected. Isolating the factors conditioning prescription that
      can be modified helps find ways to improve PPI.

PMID- 12061992
TI  - [Anamnesis is supported by diagnostic tests].

PMID- 12061993
TI  - [Use of opiate analgesics in terminal cancer patients during the last two months
      of life].

PMID- 12061996
TI  - [Studies that measure morbidity].

PMID- 12061994
TI  - [Vision disorders secondary to clomiphene citrate treatment prior to in vitro
      fertilization].

PMID- 12061997
TI  - [Usefulness of cytosolic tissue-type plasminogen activator levels in lung
      adenocarcinomas].
AB  - BACKGROUND: We aimed at studying the behavior of cytosol tissue-type plasminogen
      activator (t-PA) levels in lung adenocarcinomas and their correlation with other
      clinical and biological parameters. MATERIAL AND METHOD: t-PA cytosol levels were
      determined using EIA (Boehringer Mannheim. Germany) in 59 samples of lung
      adenocarcinoma and in 16 samples of normal lung tissue from the same patients.
      Cathepsin D, CA125, pS2, hyaluronic acid (HA), free beta subunit of chorionic
      gonadotropin hormone and neuron specific enolase (NSE) cytosol concentrations
      were determined. We also determined the concentrations of HA, erbB2 oncoprotein,
      epidermal growth factor receptor (EGFR), CD44s, CD44v5 and CD44v6 in cell
      surfaces. The following parameters were considered: clinical stage, ploidy,
      cellular S-phase fraction and histological grade. RESULTS: In adenocarcinomas, t
      PA cytosol levels ranged from 0.1 to 14.6 ng/mg prot. (median, 1.4). These levels
      were lower than those in normal lung tissue (r, 0.1-18.6; median, 2.95 ng/mg
      prot.) but did not reach statistical significance. On the other hand, t-PA
      concentrations decreased as the clinical stage increased and were higher in stage
      I than stage II-III (p = 0.080) and stage III (p = 0.0622). No significant
      differences of t-PA levels were observed when the histological grade, ploidy and
      S-phase were considered. Adenocarcinomas with high t-PA values (> 3.7 ng/mg
      prot., representing the 75th percentile of the whole group), had lower CA125 (p =
      0.015) and erbB2 oncoprotein (p = 0.087) concentrations. CONCLUSIONS: These
      results suggest that cytosol t-PA levels are negatively correlated with tumor
      size in lung adenocarcinomas. However, the usefulness of t-PA as a prognostic
      factor needs to be clarified in further studies.

PMID- 12061998
TI  - [Hormonal replacement therapy in Spain].
AB  - BACKGROUND: The consumption of hormonal replacement therapy (HRT) in Spain is not
      known. Therefore, we have conducted a study to know the mean features of that
      consumption and to find out the prevalence of use among women older than 40.
      SUBJECTS AND METHOD: To know the consumption, we have used the information
      contained in ECOM database from the Ministry of Health regarding medicines sold
      to the Spanish Health System. Also, data gathered by the General Practitioner
      Sentinel Network of Castilla y Leon had been used. The data of consumption are
      presented in daily defined dose per 1000 women more than 40 years (DHD);
      prevalence of use per year and for ages was also estimated. RESULTS: The HRT
      consumption in Spain throughout the National Health System was 6,94 DHD in 1989
      and 39.92 DHD in 1999. The percentage of women using this therapy was 0.7% in
      1989 and 3,4 in 1999; the group 50-54 years had the highest prevalence of use,
      10,84% (IC 95%, 10.66-11.01). CONCLUSIONS: The release into the market of those
      transdermal forms of HRT facilitated an increase in the consumption. Nonetheless,
      the proportion of postmenopausal women on HRT in Spain is lower than that of the
      other countries from the European Union. The proportion of women treated with
      estrogens and progestins is also small compared with current recommendations.

PMID- 12061999
TI  - [Secondary prevention of myocardial infarction and health-related quality of
      life].
AB  - BACKGROUND: Substantial evidence from randomized controlled trials reveals that
      pharmacological interventions in people with established ischemic coronary events
      notably reduces the risk of cardiovascular mortality and morbidity. The objective
      of this study was to assess potential control level of modifiable risk factors as
      well as of prophylactic treatment and quality of life in patients with a first
      myocardial infarction. METHOD: Prospective, 2-years follow-up study, carried out
      in 4 public hospitals and in their corresponding primary care centers in
      Catalonia. RESULTS: We included 618 patients (76% males) with a mean age of 64
      years. Patients were mostly followed up by both general practitioners and
      cardiologists. Prevalence of risk factors was as follows: 54% patients had
      hypercholesterolemia, 41% were hypertensive, 11% smokers, 76% had overweight and
      19% were obese. With regard to the prophylactic treatment, lipid lowering drugs
      were prescribed in 52% of patients, beta-blockers in 50%, antiplatelet drugs in
      87%, ACE inhibitors in 32%, nitrates in 52%, calcium antagonists in 31% and oral
      anticoagulants in 8% of patients. Mean scores of the quality of life
      questionnaire were 5.34, 5.42 and 5.63 for emotional role, physical role and
      social role, respectively; the subgroup of patients who were hospitalized during
      the follow up had worse scores. CONCLUSIONS: There is still a considerable
      potential to gain in the secondary prevention of myocardial infarction with
      regard to the prophylactic treatment and the control of risk factors. Health
      related quality of life in patients, two years after the first myocardial
      infarction, is fairly good, although differences between subgroups are observed.

PMID- 12062000
TI  - [Outbreak of foodborne disease by Norwalk-like viruses genogroup II].
AB  - BACKGROUND: Our goal was to investigate the epidemiological characteristics and
      etiology of an outbreak of food-borne disease caused by Norwalk-like viruses,
      genogroup II. PATIENTS AND METHOD: We performed a historical cohort study on the
      consumption of 21 food items and clinical symptoms. We assessed RNA Norwalk-like
      viruses by RT- PCR in stool samples from 5 patients and 2 food-handlers. The
      potential involvement of each food item was assessed by relative risk at 95%
      confidence intervals (CI). RESULTS: The overall attack rate was 70.0% (7/10). The
      median incubation period was 35.0 hours. Symptoms included: vomits 85.7% (6/7),
      fever 85.7% (6/7) and diarrhoea 71.4% (5/7). Four food items were involved [fish
      (RR = 1.7; CI 95% 0.9-3.3); 'selection of cold meats' (RR = 1.6; CI 95% 0.9-2.7);
      yoghurt (RR = 1.5; CI 95% 1.0-2.4) and lamb (RR = 1.3; CI 95% 0.6-3.0)]. Three
      stool sample gave positive results for Norwalk-like viruses genogroup II.
      Important oversights in food-handlers' work were detected. CONCLUSIONS: RT-PCR
      enabled us to confirm the etiology of this outbreak as Norwalk-like viruses
      genogroup II. Although patients recovered quickly, the outbreak caused
      considerable public alarm.

PMID- 12062001
TI  - [Tourist-class syndrome].

PMID- 12062002
TI  - [What is good for the patient?].

PMID- 12062003
TI  - [Stress, cardiovascular disease and hypertension].

PMID- 12062004
TI  - [Artificial blood and other measures aimed at reducing allogeneic blood
      transfusion].

PMID- 12062005
TI  - [Hyperkalemia and celecoxib].

PMID- 12062006
TI  - [Intestinal parasitological study in immigrants in the region of Safor (Comunidad
      Valeciana), Spain].

PMID- 12062007
TI  - [Clopidogrel probably induced hepatic toxicity].

PMID- 12062008
TI  - [Sudden death attributed to ventricular arrhytmia induced by an over-the-counter
      drug for influenza].

PMID- 12062009
TI  - [Levofloxacin and acute confusional syndrome].

PMID- 12062010
TI  - [Metal fume fever].

PMID- 12062013
TI  - Needle from a haystack. Optimal signaling by a nonlinear synapse.
AB  - Commonly, a neuron must separate a small, rare event carried by one of its inputs
      from the noise carried by many others. In this issue of Neuron, demonstrate that
      to solve this problem, the rod bipolar neuron in mouse retina selectively
      amplifies a rod's single-photon signal only when it is larger than average. This
      nonlinearity rejects nearly three-fourths of the single-photon signals. Yet, by
      also rejecting noise, it provides nearly optimal filtering near absolute visual
      threshold.

PMID- 12062012
TI  - Toward cell specificity in SCA1.
AB  - Transcriptional dysregulation appears as an emerging and unifying pathogenic
      mechanism in polyQ neurodegenerative disorders such as Spinocerebellar ataxias
      and Huntington's disease. It is unclear how cell death specificity occurs in
      these diseases. In this issue of Neuron, link polymerase II, a general component
      of the transcriptional machinery, to PQBP-1, a cerebellar enriched protein, thus
      providing insight into the selectivity of neuronal death in SCA1.

PMID- 12062014
TI  - Reaching for answers.
AB  - The exact function of motor cortex continues to be an enigma. In this issue of
      Neuron, present provocative data showing that microstimulation of the precentral
      cortex evokes complex movements, and conclude that the motor and premotor cortex
      together may form a single map of complex postures.

PMID- 12062015
TI  - Kallmann syndrome: adhesion, afferents, and anosmia.
AB  - Three new studies into the function of human anosmin-1 and related proteins in C.
      elegans and rodents show that these influence axon branching and axon targeting.
      The rodent anosmin appears to work at two stages of development, initially
      promoting axon outgrowth from the olfactory bulb and then stimulating branching
      from axons into the olfactory cortex. CeKal-1 further influences morphogenesis,
      and, as the human and nematode anosmins are functionally conserved, these studies
      provide insights into the pathogenesis of Kallmann syndrome (KS).

PMID- 12062016
TI  - Channels gone bad. Reflections from a Tapas bar.

PMID- 12062017
TI  - Magnetic resonance imaging of neuronal connections in the macaque monkey.
AB  - Recently, an MRI-detectable, neuronal tract-tracing method in living animals was
      introduced that exploits the anterograde transport of manganese (Mn2+). We
      present the results of experiments simultaneously tracing manganese chloride and
      wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) to evaluate
      the specificity of the former by tracing the neuronal connections of the basal
      ganglia of the monkey. Mn2+ and WGA-HRP yielded remarkably similar and highly
      specific projection patterns. By showing the sequential transport of Mn2+ from
      striatum to pallidum-substantia nigra and then to thalamus, we demonstrated MRI
      visualization of transport across at least one synapse in the CNS of the primate.
      Transsynaptic tract tracing in living primates will allow chronic studies of
      development and plasticity and provide valuable anatomical information for fMRI
      and electrophysiological experiments in primates.

PMID- 12062018
TI  - Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell
      death.
AB  - PQBP-1 was isolated on the basis of its interaction with polyglutamine tracts. In
      this study, using in vitro and in vivo assays, we show that the association
      between ataxin-1 and PQBP-1 is positively influenced by expanded polyglutamine
      sequences. In cell lines, interaction between the two molecules induces apoptotic
      cell death. As a possible mechanism underlying this phenomenon, we found that
      mutant ataxin-1 enhances binding of PQBP-1 to the C-terminal domain of RNA
      polymerase II large subunit (Pol II). This reduces the level of phosphorylated
      Pol II and transcription. Our results suggest the involvement of PQBP-1 in the
      pathology of spinocerebellar ataxia type 1 (SCA1) and support the idea that
      modified transcription underlies polyglutamine-mediated pathology.

PMID- 12062019
TI  - Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing
      late-onset progressive degeneration.
AB  - To test the hypothesis that inhibition of axonal transport is sufficient to cause
      motor neuron degeneration such as that observed in amyotrophic lateral sclerosis
      (ALS), we engineered a targeted disruption of the dynein-dynactin complex in
      postnatal motor neurons of transgenic mice. Dynamitin overexpression was found to
      disassemble dynactin, a required activator of cytoplasmic dynein, resulting in an
      inhibition of retrograde axonal transport. Mice overexpressing dynamitin
      demonstrate a late-onset progressive motor neuron degenerative disease
      characterized by decreased strength and endurance, motor neuron degeneration and
      loss, and denervation of muscle. Previous transgenic mouse models of ALS have
      shown abnormalities in microtubule-based axonal transport. In this report, we
      describe a mouse model that confirms the critical role of disrupted axonal
      transport in the pathogenesis of motor neuron degenerative disease.

PMID- 12062020
TI  - Dynactin is necessary for synapse stabilization.
AB  - We present evidence that synapse retraction occurs during normal synaptic growth
      at the Drosophila neuromuscular junction (NMJ). An RNAi-based screen to identify
      the molecular mechanisms that regulate synapse retraction identified Arp
      1/centractin, a subunit of the dynactin complex. Arp-1 dsRNA enhances synapse
      retraction, and this effect is phenocopied by a mutation in P150/Glued, also a
      dynactin component. The Glued protein is enriched within the presynaptic nerve
      terminal, and presynaptic expression of a dominant-negative Glued transgene
      enhances retraction. Retraction is associated with a local disruption of the
      synaptic microtubule cytoskeleton. Electrophysiological, ultrastructural, and
      immunohistochemical data support a model in which presynaptic retraction precedes
      disassembly of the postsynaptic apparatus. Our data suggests that dynactin
      functions locally within the presynaptic arbor to promote synapse stability.

PMID- 12062021
TI  - Extensive editing of mRNAs for the squid delayed rectifier K+ channel regulates
      subunit tetramerization.
AB  - We report the extensive editing of mRNAs that encode the classical delayed
      rectifier K+ channel (SqK(v)1.1A) in the squid giant axon. Using a quantitative
      RNA editing assay, 14 adenosine to guanine transitions were identified, and
      editing efficiency varied tremendously between positions. Interestingly, half of
      the sites are targeted to the T1 domain, important for subunit assembly. Other
      sites occur in the channel's transmembrane spans. The effects of editing on K+
      channel function are elaborate. Edited codons affect channel gating, and several
      T1 sites regulate functional expression as well. In particular, the edit R87G, a
      phylogenetically conserved position, reduces expression close to 50-fold by
      regulating the channel's ability to form tetramers. These data suggest that RNA
      editing plays a dynamic role in regulating action potential repolarization in the
      giant axon.

PMID- 12062022
TI  - RNA editing at arg607 controls AMPA receptor exit from the endoplasmic reticulum.
AB  - AMPA-receptor (AMPAR) transport to synapses plays a critical role in the
      modulation of synaptic strength. We show that the functionally critical GluR2
      subunit stably resides in an intracellular pool in the endoplasmic reticulum
      (ER). GluR2 in this pool is extensively complexed with GluR3 but not with GluR1,
      which is mainly confined to the cell surface. Mutagenesis revealed that elements
      in the C terminus including the PDZ motif are required for GluR2 forward
      transport from the ER. Surprisingly, ER retention of GluR2 is controlled by
      Arg607 at the Q/R-editing site. Reversion to Gln (R607Q) resulted in rapid
      release from the pool and elevated surface expression of GluR2 in neurons.
      Therefore, Arg607 is a central regulator. In addition to channel gating, it also
      controls ER exit and may thereby ensure the availability of GluR2 for assembly
      into AMPARs.

PMID- 12062023
TI  - Nonlinear signal transfer from mouse rods to bipolar cells and implications for
      visual sensitivity.
AB  - We investigated the impact of rod-bipolar signal transfer on visual sensitivity.
      Two observations indicate that rod-rod bipolar signal transfer is nonlinear.
      First, responses of rods increased linearly with flash strength, while those of
      rod bipolars increased supralinearly. Second, fluctuations in the responses of
      rod bipolars were larger than expected from linear summation of the rod inputs.
      Rod-OFF bipolar signal transfer did not share this strong nonlinearity.
      Surprisingly, nonlinear rod-rod bipolar signal transfer eliminated many of the
      rod's single-photon responses. The impact on sensitivity, however, was more than
      compensated for by rejection of noise from rods that did not absorb photons. As a
      consequence, rod bipolars provide a near-optimal readout of rod signals at light
      levels near visual threshold.

PMID- 12062024
TI  - Inhibition of interneuron firing extends the spread of endocannabinoid signaling
      in the cerebellum.
AB  - Endocannabinoids serve as retrograde messengers in many brain regions. These
      diffusible lipophilic molecules are released by postsynaptic cells and regulate
      presynaptic neurotransmitter release. Here we describe an additional mechanism
      that mediates the spread of endocannabinoid signaling to distant inhibitory
      synapses. Depolarization of cerebellar Purkinje cells reduced the firing rate of
      nearby interneurons, and this reduction in firing was blocked by the cannabinoid
      receptor antagonist AM251. The cannabinoid receptor agonist WIN55,212-2 also
      reduced firing rates in interneurons, and this inhibition arose from the
      activation of a small potassium conductance. Thus, endocannabinoids released from
      the dendrites of depolarized neurons can lead to inhibition of firing in nearby
      cells. Because interneurons can project over several hundred micrometers, this
      inhibition of firing allows cells to regulate synaptic inputs at distances well
      beyond the limits of endocannabinoid diffusion.

PMID- 12062025
TI  - Reciprocal bidirectional plasticity of parallel fiber receptive fields in
      cerebellar Purkinje cells and their afferent interneurons.
AB  - The highly specific relationships between parallel fiber (PF) and climbing fiber
      (CF) receptive fields in Purkinje cells and interneurons suggest that normal PF
      receptive fields are established by CF-specific plasticity. To test this idea, we
      used PF stimulation that was either paired or unpaired with CF activity.
      Conspicuously, unpaired PF stimulation that induced long-lasting, very large
      increases in the receptive field sizes of Purkinje cells induced long-lasting
      decreases in receptive field sizes of their afferent interneurons. In contrast,
      PF stimulation paired with CF activity that induced long-lasting decreases in the
      receptive fields of Purkinje cells induced long-lasting, large increases in the
      receptive fields of interneurons. These properties, and the fact the mossy fiber
      receptive fields were unchanged, suggest that the receptive field changes were
      due to bidirectional PF synaptic plasticity in Purkinje cells and interneurons.

PMID- 12062026
TI  - Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and
      facilitates striatal-mediated learning and memory.
AB  - Extracellular signal-regulated kinases (ERK1 and 2) are synaptic signaling
      components necessary for several forms of learning. In mice lacking ERK1, we
      observe a dramatic enhancement of striatum-dependent long-term memory, which
      correlates with a facilitation of long-term potentiation in the nucleus
      accumbens. At the cellular level, we find that ablation of ERK1 results in a
      stimulus-dependent increase of ERK2 signaling, likely due to its enhanced
      interaction with the upstream kinase MEK. Consistently, such activity change is
      responsible for the hypersensitivity of ERK1 mutant mice to the rewarding
      properties of morphine. Our results reveal an unexpected complexity of ERK
      dependent signaling in the brain and a critical regulatory role for ERK1 in the
      long-term adaptive changes underlying striatum-dependent behavioral plasticity
      and drug addiction.

PMID- 12062027
TI  - Respiratory rhythm: an emergent network property?
AB  - We tested the hypothesis that pacemaker neurons generate breathing rhythm in
      mammals. We monitored respiratory-related motor nerve rhythm in neonatal rodent
      slice preparations. Blockade of the persistent sodium current (I(NaP)), which was
      postulated to underlie voltage-dependent bursting in respiratory pacemaker
      neurons, with riluzole (< or =200 microM) did not alter the frequency of
      respiratory-related motor output. Yet, in every pacemaker neuron recorded
      (50/50), bursting was abolished at much lower concentrations of riluzole (< or
      =20 microM). Thus, eliminating the pacemaker population (our statistics confirm
      that this population is reduced at least 94%, p < 0.05) does not affect
      respiratory rhythm. These results suggest that voltage-dependent bursting in
      pacemaker neurons is not essential for respiratory rhythmogenesis, which may
      instead be an emergent network property.

PMID- 12062028
TI  - Driving plasticity in human adult motor cortex is associated with improved motor
      function after brain injury.
AB  - Changes in somatosensory input can remodel human cortical motor organization, yet
      the input characteristics that promote reorganization and their functional
      significance have not been explored. Here we show with transcranial magnetic
      stimulation that sensory-driven reorganization of human motor cortex is highly
      dependent upon the frequency, intensity, and duration of stimulus applied. Those
      patterns of input associated with enhanced excitability (5 Hz, 75% maximal
      tolerated intensity for 10 min) induce stronger cortical activation to fMRI. When
      applied to acutely dysphagic stroke patients, swallowing corticobulbar
      excitability is increased mainly in the undamaged hemisphere, being strongly
      correlated with an improvement in swallowing function. Thus, input to the human
      adult brain can be programmed to promote beneficial changes in neuroplasticity
      and function after cerebral injury.

PMID- 12062029
TI  - Complex movements evoked by microstimulation of precentral cortex.
AB  - Electrical microstimulation was used to study primary motor and premotor cortex
      in monkeys. Each stimulation train was 500 ms in duration, approximating the time
      scale of normal reaching and grasping movements and the time scale of the
      neuronal activity that normally accompanies movement. This stimulation on a
      behaviorally relevant time scale evoked coordinated, complex postures that
      involved many joints. For example, stimulation of one site caused the mouth to
      open and also caused the hand to shape into a grip posture and move to the mouth.
      Stimulation of this site always drove the joints toward this final posture,
      regardless of the direction of movement required to reach the posture.
      Stimulation of other cortical sites evoked different postures. Postures that
      involved the arm were arranged across cortex to form a map of hand positions
      around the body. This stimulation-evoked map encompassed both primary motor and
      the adjacent premotor cortex. We suggest that these regions fit together into a
      single map of the workspace around the body.

PMID- 12062030
TI  - A dorsal elaboration in the spinal cord.
AB  - Functionally distinct types of neurons develop in stereotypical positions in the
      vertebrate spinal cord. The mechanisms that generate this diversity have been
      well studied in the ventral and intermediate regions of the spinal cord, while
      dorsal cells have received less attention. In this issue of Neuron, two papers
      focusing on dorsal interneuron development level the playing field.

PMID- 12062031
TI  - Multisensory integration in cortex: shedding light on prickly issues.
AB  - Interactions between different sensory modalities can be observed in unimodal
      areas of the cortex, as revealed by recent neuroimaging studies. A new report by
      Macaluso and colleagues ( [this issue of Neuron]) shows that crossmodal effects
      of tactile stimulation in visual cortex critically depend on the spatial
      congruence of multisensory inputs. This work is discussed in relation to neural
      and computational models of multisensory integration.

PMID- 12062032
TI  - Correlations between the fMRI BOLD signal and visual perception.
AB  - Using fMRI and a psychophysical task involving letter identification,
      Kleinschmidt et al. (2002) (this issue of Neuron) delineate two patterns of
      neural activation, which manifest in different cortical regions: a transient
      activation, correlated with the change of a percept, and a longer-term
      hysteresis, correlated with the maintenance of the percept. These findings are
      provocative and suggest that neural hysteresis is mediated by visual structures
      that interact with higher-order regions to support longer-term maintenance of a
      percept.

PMID- 12062033
TI  - A RIP tide in neuronal signal transduction.
AB  - The generation of nuclear signaling proteins by regulated intramembrane
      proteolysis (RIP) is a new paradigm of signal transduction. Mammalian proteins
      that are processed by RIP include SREBP-1, Notch-1, amyloid precursor protein
      (APP), and ErbB-4. Intramembranous gamma-secretase cleavage of APP plays a
      central role in Alzheimer's disease by generating the amyloid beta protein. An
      intriguing possibility is that the cognate C-terminal fragment generated by gamma
      secretase cleavage could also play a role through the regulation of nuclear
      signaling events. Thus, RIP may contribute to both brain development and
      degeneration and may provide unexpected diversity to the signaling repertoire of
      a cell.

PMID- 12062034
TI  - Shedding light on vertebrate magnetoreception.
AB  - We review the challenges and recent progress in elucidating the physiological
      basis of animal magnetoreception. Behavioral and theoretical studies suggest a
      link between photoreception and magnetoreception in some animals.
      Neurophysiological studies have the potential to prove this link and identify the
      location of and the mechanism underlying the magnetoreception system.

PMID- 12062036
TI  - Human wild-type tau interacts with wingless pathway components and produces
      neurofibrillary pathology in Drosophila.
AB  - Pathologic alterations in the microtubule-associated protein tau have been
      implicated in a number of neurodegenerative disorders, including Alzheimer's
      disease (AD), progressive supranuclear palsy (PSP), and frontotemporal dementia
      (FTD). Here, we show that tau overexpression, in combination with phosphorylation
      by the Drosophila glycogen synthase kinase-3 (GSK-3) homolog and wingless pathway
      component (Shaggy), exacerbated neurodegeneration induced by tau overexpression
      alone, leading to neurofibrillary pathology in the fly. Furthermore, manipulation
      of other wingless signaling molecules downstream from shaggy demonstrated that
      components of the Wnt signaling pathway modulate neurodegeneration induced by tau
      pathology in vivo but suggested that tau phosphorylation by GSK-3beta differs
      from canonical Wnt effects on beta-catenin stability and TCF activity. The
      genetic system we have established provides a powerful reagent for identification
      of novel modifiers of tau-induced neurodegeneration that may serve as future
      therapeutic targets.

PMID- 12062037
TI  - Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing
      A53T human alpha-synuclein.
AB  - alpha-Synucleinopathies are neurodegenerative disorders that range pathologically
      from the demise of select groups of nuclei to pervasive degeneration throughout
      the neuraxis. Although mounting evidence suggests that alpha-synuclein lesions
      lead to neurodegeneration, this remains controversial. To explore this issue, we
      generated transgenic mice expressing wild-type and A53T human alpha-synuclein in
      CNS neurons. Mice expressing mutant, but not wild-type, alpha-synuclein developed
      a severe and complex motor impairment leading to paralysis and death. These
      animals developed age-dependent intracytoplasmic neuronal alpha-synuclein
      inclusions paralleling disease onset, and the alpha-synuclein inclusions
      recapitulated features of human counterparts. Moreover, immunoelectron microscopy
      revealed that the alpha-synuclein inclusions contained 10-16 nm wide fibrils
      similar to human pathological inclusions. These mice demonstrate that A53T alpha
      synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal
      inclusions that cause neurodegeneration.

PMID- 12062038
TI  - Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord.
AB  - Association and relay neurons that are generated in the dorsal spinal cord play
      essential roles in transducing somatosensory information. During development,
      these two major neuronal classes are delineated by the expression of the
      homeodomain transcription factor Lbx1. Lbx1 is expressed in and required for the
      correct specification of three early dorsal interneuron populations and late-born
      neurons that form the substantia gelatinosa. In mice lacking Lbx1, cells types
      that arise in the ventral alar plate acquire more dorsal identities. This results
      in the loss of dorsal horn association interneurons, excess production of
      commissural neurons, and disrupted sensory afferent innervation of the dorsal
      horn. Lbx1, therefore, plays a critical role in the development of sensory
      pathways in the spinal cord that relay pain and touch.

PMID- 12062039
TI  - The homeodomain factor lbx1 distinguishes two major programs of neuronal
      differentiation in the dorsal spinal cord.
AB  - Dorsal horn neurons in the spinal cord integrate and relay sensory information.
      Here, we show that the expression of the homeobox gene Lbx1 distinguishes two
      major neuronal classes generated in the dorsal spinal cord. The Lbx1(-) (class A)
      and Lbx1(+) (class B) neurons differ in their dependence on roof plate BMP
      signals for specification and settle in the deep and superficial dorsal horn,
      respectively. Lbx1 misexpression blocks the differentiation of class A neurons.
      Conversely, in Lbx1 mutant mice, class B neurons assume the identity of class A
      neurons. As a consequence, the morphology and neuronal circuitry of the dorsal
      horn are aberrant. We conclude that Lbx1 distinguishes two major neuronal classes
      in the dorsal spinal cord and is an important determinant of their distinct
      differentiation programs.

PMID- 12062040
TI  - MAX-1, a novel PH/MyTH4/FERM domain cytoplasmic protein implicated in netrin
      mediated axon repulsion.
AB  - The netrin UNC-6 repels motor axons by activating the UNC-5 receptor alone or in
      combination with the UNC-40/DCC receptor. In a genetic screen for C. elegans
      mutants exhibiting partial defects in motor axon projections, we isolated the max
      1 gene (required for motor neuron axon guidance). max-1 loss-of-function
      mutations cause fully penetrant but variable axon guidance defects. Mutations in
      unc-5 and unc-6, but not in unc-40, dominantly enhance the mutant phenotypes of
      max-1, whereas overexpression of unc-5 or unc-6, but not of unc-40, bypasses the
      requirement for max-1. MAX-1 proteins contain PH, MyTH4, and FERM domains and
      appear to be localized to neuronal processes. Human MAX-1 and UNC5H2 colocalize
      in discrete subcellular regions of transfected cells. Our results suggest a
      possible role for MAX-1 in netrin-induced axon repulsion by modulating the UNC-5
      receptor signaling pathway.

PMID- 12062041
TI  - Migration and function of a glial subtype in the vertebrate peripheral nervous
      system.
AB  - Glia-axon interactions are essential for the development and function of the
      nervous system. We combine in vivo imaging and genetics to address the mechanism
      by which the migration of these cells is coordinated during embryonic
      development. Using stable transgenic lines, we have followed the migration of one
      subset of glial cells and their target axons in living zebrafish embryos. These
      cells coalesce at an early stage and remain coupled throughout migration, with
      axons apparently pathfinding for glia. Mutant analysis demonstrates that axons
      provide instructive cues that are sufficient to control glial guidance.
      Furthermore, mutations in the transcription factor Sox10/cls uncouple the
      migration of axons and glia. Finally, genetic ablation of this glial subtype
      reveals an essential role in nerve fasciculation.

PMID- 12062042
TI  - Differential activation of individual subunits in heteromeric kainate receptors.
AB  - Neuronal kainate receptors are assembled from subunits with dissimilar
      specificities for agonists and antagonists. The composite biophysical behavior of
      heteromeric kainate receptors is determined by intersubunit interactions whose
      nature is unclear. Here we use dysiherbaine, a selective kainate receptor
      agonist, to show that GluR5 subunits assembled in heteromeric GluR5/KA-2 kainate
      receptor complexes can gate current without concomitant activation of their
      partner KA-2 subunits. A long-lasting interaction between dysiherbaine and GluR5
      subunits elicits a tonic current from GluR5/KA-2 receptors; subsequent
      cooperative gating of KA-2 subunits can be elicited by both agonists, such as
      glutamate, and some classically defined antagonists, such as CNQX. This study
      demonstrates that each type of subunit within a heteromeric kainate receptor
      contributes a distinct conductance upon activation by agonist binding, and
      therefore provides insight into the biophysical function of ionotropic glutamate
      receptors.

PMID- 12062043
TI  - Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered
      exocytosis.
AB  - Synaptotagmin is a proposed Ca2+ sensor on the vesicle for regulated exocytosis
      and exhibits Ca2+-dependent binding to phospholipids, syntaxin, and SNAP-25 in
      vitro, but the mechanism by which Ca2+ triggers membrane fusion is uncertain.
      Previous studies suggested that SNAP-25 plays a role in the Ca2+ regulation of
      secretion. We found that synaptotagmins I and IX associate with SNAP-25 during
      Ca2+-dependent exocytosis in PC12 cells, and we identified C-terminal amino acids
      in SNAP-25 (Asp179, Asp186, Asp193) that are required for Ca2+-dependent
      synaptotagmin binding. Replacement of SNAP-25 in PC12 cells with SNAP-25
      containing C-terminal Asp mutations led to a loss-of-function in regulated
      exocytosis at the Ca2+-dependent fusion step. These results indicate that the
      Ca2+-dependent interaction of synaptotagmin with SNAP-25 is essential for the
      Ca2+-dependent triggering of membrane fusion.

PMID- 12062044
TI  - A single packet of transmitter does not saturate postsynaptic glutamate
      receptors.
AB  - Neurotransmitter is stored in synaptic vesicles and released by exocytosis into
      the synaptic cleft. One of the fundamental questions in central synaptic
      transmission is whether a quantal packet of transmitter saturates postsynaptic
      receptors. To address this question, we loaded the excitatory transmitter L
      glutamate via whole-cell recording pipettes into the giant nerve terminal, the
      calyx of Held, in rat brainstem slices. This caused marked potentiations of both
      quantal and action potential-evoked EPSCs mediated by alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors.
      These results directly demonstrate that neither AMPA nor NMDA receptors are
      saturated by a single packet of transmitter, and indicate that vesicular
      transmitter content is an important determinant of synaptic efficacy.

PMID- 12062045
TI  - Visually driven modulation of glutamatergic synaptic transmission is mediated by
      the regulation of intracellular polyamines.
AB  - Ca2+-permeable AMPARs are inwardly rectifying due to block by intracellular
      polyamines. Neuronal activity regulates polyamine synthesis, yet whether this
      affects Ca2+-AMPAR-mediated synaptic transmission is unknown. We test whether 4
      hr of increased visual stimulation regulates glutamatergic retino-tectal synapses
      in Xenopus tadpoles. Tectal neurons containing Ca2+-AMPARs form a gradient along
      the rostro-caudal developmental axis. These neurons had inwardly rectifying AMPAR
      mediated EPSCs. Four hours of visual stimulation or addition of intracellular
      spermine increased rectification in immature neurons. Polyamine synthesis
      inhibitors blocked the effect of visual stimulation, suggesting that visual
      activity regulates AMPARs via the polyamine synthesis pathway. This modulation
      resulted in changes in the integrative properties of tectal neurons. Regulation
      of polyamine synthesis by physiological stimuli is a novel form of modulation of
      synaptic transmission important for understanding the short-term effects of
      enhanced sensory experience during development.

PMID- 12062046
TI  - A presynaptic kainate receptor is involved in regulating the dynamic properties
      of thalamocortical synapses during development.
AB  - Previous studies have shown that pharmacological activation of presynaptic
      kainate receptors at glutamatergic synapses facilitates or depresses transmission
      in a dose-dependent manner. However, the only synaptically activated kainate
      autoreceptor described to date is facilitatory. Here, we describe a kainate
      autoreceptor that depresses synaptic transmission. This autoreceptor is present
      at developing thalamocortical synapses in the barrel cortex, specifically
      regulates transmission at frequencies corresponding to those observed in vivo
      during whisker activation, and is developmentally down regulated during the first
      postnatal week. This receptor may, therefore, limit the transfer of high
      frequency activity to the developing cortex, the loss of which mechanism may be
      important for the maturation of sensory processing.

PMID- 12062047
TI  - Crossmodal spatial influences of touch on extrastriate visual areas take current
      gaze direction into account.
AB  - Recent results indicate that crossmodal interactions can affect activity in
      cortical regions traditionally regarded as "unimodal." Previously we found that
      combining touch on one hand with visual stimulation in the anatomically
      corresponding hemifield could boost responses in contralateral visual cortex.
      Here we manipulated which visual hemifield corresponded to the location of the
      stimulated hand, by changing gaze direction such that right-hand touch could now
      arise in either the left or right visual field. Crossmodal effects on visual
      cortex switched from one hemisphere to the other, depending on gaze direction,
      regardless of whether the hand was seen. This indicates that crossmodal
      influences of touch upon visual cortex depend on spatial alignment for the
      multimodal stimuli, with gaze posture taken into account.

PMID- 12062048
TI  - The neural structures expressing perceptual hysteresis in visual letter
      recognition.
AB  - Perception can change nonlinearly with stimulus contrast, and perceptual
      threshold may depend on the direction of contrast change. Such hysteresis effects
      in neurometric functions provide a signature of perceptual awareness. We recorded
      brain activity with functional neuroimaging in observers exposed to gradual
      contrast changes of initially hidden visual stimuli. Lateral occipital, frontal,
      and parietal regions all displayed both transient activations and hysteresis that
      correlated with change and maintenance of a percept, respectively. Medial
      temporal activity did not follow perception but increased during hysteresis and
      showed transient deactivations during perceptual transitions. These findings
      identify a set of brain regions sensitive to visual awareness and suggest that
      medial temporal structures may provide backward signals that account for neural
      and, thereby, perceptual hysteresis.

PMID- 12062049
TI  - Control of replication timing by a transcriptional silencer.
AB  - BACKGROUND: Eukaryotic DNA replication starts at many origins. Some origins are
      used early in S phase, while others are programmed to fire later. In general,
      late replication is correlated with transcriptional inactivity and with location
      near the nuclear periphery. However, the mechanisms that determine replication
      timing are unclear, and the cause-and-effect relationship between late
      replication, transcriptional inactivity, and location at the nuclear periphery is
      unknown. RESULTS: Using budding yeast, we show that a transcriptional silencer,
      HMR-E, can reset the time of initiation of ARS305 from early to late. This
      resetting requires Sir proteins, which are silencers of transcription. Resetting
      can also be achieved by targeting Sir4 to ARS305. HMR-E sequences and targeted
      Sir4, both of which cause late replication of ARS305, also cause transcriptional
      silencing of the nearby APA1 gene. CONCLUSIONS: Sir proteins are sufficient to
      reprogram an origin from early to late; that is, Sir proteins are a cause of late
      replication. Presumably, the tight chromatin structure promoted by Sir proteins
      favors both transcriptional inactivity and late replication.

PMID- 12062050
TI  - Zebrafish Rho kinase 2 acts downstream of Wnt11 to mediate cell polarity and
      effective convergence and extension movements.
AB  - BACKGROUND: During vertebrate gastrulation convergence and extension (CE),
      movements narrow and lengthen embryonic tissues. In Xenopus and zebrafish, a
      noncanonical Wnt signaling pathway constitutes the vertebrate counterpart to the
      Drosophila planar cell polarity pathway and regulates mediolateral cell
      polarization underlying CE. Despite the identification of several signaling
      molecules required for normal CE, the downstream transducers regulating
      individual cell behaviors driving CE are only beginning to be elucidated.
      Moreover, how defective mediolateral cell polarity impacts CE is not understood.
      RESULTS: Here, we show that overexpression of zebrafish dominant-negative Rho
      kinase 2 (dnRok2) disrupts CE without altering cell fates, phenocopying
      noncanonical Wnt signaling mutants. Moreover, Rho kinase 2 (Rok2) overexpression
      partially suppresses the slb/wnt11 gastrulation phenotype, and ectopic expression
      of noncanonical Wnts modulates Rok2 intracellular distribution. In addition, time
      lapse analyses associate defective dorsal convergence movements with impaired
      cell elongation, mediolateral orientation, and consequently failure to migrate
      along straight paths. Transplantation experiments reveal that dnRok2 cells in
      wild-type hosts neither elongate nor orient their axes. In contrast, wild-type
      cells are able to elongate their cell bodies in dnRok2 hosts, even though they
      fail to orient their axes. CONCLUSIONS: During zebrafish gastrulation, Rok2 acts
      downstream of noncanonical Wnt11 signaling to mediate mediolateral cell
      elongation required for dorsal cell movement along straight paths. Furthermore,
      elongation and orientation of the cell body are independent properties that
      require both cell-autonomous and nonautonomous Rok2 function.

PMID- 12062051
TI  - Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking
      to the multivesicular body.
AB  - BACKGROUND: The PtdIns3P 5-kinase Fab1 makes PtdIns(3,5)P(2), a phosphoinositide
      essential for retrograde trafficking between the vacuole/lysosome and the late
      endosome and also for trafficking of some proteins into the vacuole via
      multivesicular bodies (MVB). No regulators of Fab1 were identified until
      recently. RESULTS: Visual screening of the Eurofan II panel of S. cerevisiae
      deletion mutants identified YLR386w as a novel regulator of vacuolar function.
      Others recently identified this ORF as encoding the vacuolar inheritance gene
      VAC14. Like fab1 mutants, yeast lacking Vac14 have enlarged vacuoles that do not
      acidify correctly. FAB1 overexpression corrects these defects. vac14Delta cells
      make very little PtdIns(3,5)P(2), and hyperosmotic shock does not stimulate
      PtdIns(3,5)P(2) synthesis in the normal manner, implicating Vac14 in Fab1
      regulation. We also show that, like fab1Delta mutants, vac14Delta cells fail to
      sort GFP-Phm5 to the MVB and thence to the vacuole: irreversible ubiquitination
      of GFP-Phm5 overcomes this defect. In the BY4742 genetic background, loss of
      Vac14 causes much more penetrant effects on phosphoinositide metabolism and
      vacuolar trafficking than does loss of Vac7, another regulator of Fab1. Vac14
      contains motifs suggestive of a role in protein trafficking and interacts with
      several proteins involved in clathrin-mediated membrane sorting and
      phosphoinositide metabolism. CONCLUSIONS: Vac14 and Vac7 are both upstream
      activators of Fab1-catalysed PtdIns(3,5)P(2) synthesis, with Vac14 the dominant
      contributor to the hierarchy of control. Vac14 is essential for the regulated
      synthesis of PtdIns(3,5)P(2), for control of trafficking of some proteins to the
      vacuole lumen via the MVB, and for maintenance of vacuole size and acidity.

PMID- 12062052
TI  - The kinase activity of aurora B is required for kinetochore-microtubule
      interactions during mitosis.
AB  - As a component of the "chromosomal passenger protein complex," the aurora B
      kinase is associated with centromeres during prometaphase and with midzone
      microtubules during anaphase and is required for both mitosis and cytokinesis.
      Ablation of aurora B causes defects in both prometaphase chromosomal congression
      and the spindle checkpoint; however, the mechanisms underlying these defects are
      unclear. To address this question, we have examined chromosomal movement, spindle
      organization, and microtubule motor distribution in NRK cells transfected with a
      kinase-inactive, dominant-negative mutant of aurora B, aurora B(K-R). In cells
      overexpressing aurora B(K-R) fused with GFP, centromeres moved in a synchronized
      and predominantly unidirectional manner, as opposed to the independent,
      bidirectional movement in control cells expressing a similar level of wild-type
      aurora B-GFP. In addition, most kinetochores became physically separated from
      spindle microtubules, which appeared as a striking bundle between the spindle
      poles. These defects were associated with a microtubule-dependent depletion of
      motor proteins dynein and CENP-E from kinetochores. Our observations suggest that
      aurora B regulates the association of motor proteins with kinetochores during
      prometaphase. Interactions of kinetochore motors with microtubules may in turn
      regulate the organization of microtubules, the movement of prometaphase
      chromosomes, and the release of the spindle checkpoint.

PMID- 12062053
TI  - Inhibition of aurora B kinase blocks chromosome segregation, overrides the
      spindle checkpoint, and perturbs microtubule dynamics in mitosis.
AB  - How kinetochores correct improper microtubule attachments and regulate the
      spindle checkpoint signal is unclear. In budding yeast, kinetochores harboring
      mutations in the mitotic kinase Ipl1 fail to bind chromosomes in a bipolar
      fashion. In C. elegans and Drosophila, inhibition of the Ipl1 homolog, Aurora B
      kinase, induces aberrant anaphase and cytokinesis. To study Aurora B kinase in
      vertebrates, we microinjected mitotic XTC cells with inhibitory antibody and
      found several related effects. After injection of the antibody, some chromosomes
      failed to congress to the metaphase plate, consistent with a conserved role for
      Aurora B in bipolar attachment of chromosomes. Injected cells exited mitosis with
      no evidence of anaphase or cytokinesis. Injection of anti-Xaurora B antibody also
      altered the microtubule network in mitotic cells with an extension of the astral
      microtubules and a reduction of kinetochore microtubules. Finally, inhibition of
      Aurora B in cultured cells and in cycling Xenopus egg extracts caused escape from
      the spindle checkpoint arrest induced by microtubule drugs. Our findings
      implicate Aurora B as a critical coordinator relating changes in microtubule
      dynamics in mitosis, chromosome movement in prometaphase and anaphase, signaling
      of the spindle checkpoint, and cytokinesis.

PMID- 12062054
TI  - C. elegans class B synthetic multivulva genes act in G(1) regulation.
AB  - The single C. elegans member of the retinoblastoma gene family, lin-35 Rb, was
      originally identified as a synthetic Multivulva (synMuv) gene [1]. These genes
      form two redundant classes, A and B, that repress ectopic vulval cell fate
      induction. Recently, we demonstrated that lin-35 Rb also acts as a negative
      regulator of G(1) progression and likely is the major target of cyd-1 Cyclin D
      and cdk-4 CDK4/6. Here, we describe G(1) control functions for several other
      class B synMuv genes. We found that efl-1 E2F negatively regulates cell cycle
      entry, while dpl-1 DP appeared to act both as a positive and negative regulator.
      In addition, we identified a negative G(1) regulatory function for lin-9 ALY, as
      well as lin-15B and lin-36, which encode novel proteins. Inactivation of lin-35
      Rb, efl-1, or lin-36 allowed S phase entry in the absence of cyd-1/cdk-4 and
      increased ectopic cell division when combined with cki-1 Cip/Kip RNAi. These data
      are consistent with lin-35 Rb, efl-1, and lin-36 acting in a common pathway or
      complex that negatively regulates G(1) progression. In contrast, lin-15B appeared
      to act in parallel to lin-35. Our results demonstrate the potential for genetic
      identification of novel G(1) regulators in C. elegans.

PMID- 12062055
TI  - The mammalian mismatch repair pathway removes DNA 8-oxodGMP incorporated from the
      oxidized dNTP pool.
AB  - Mismatch repair (MMR) corrects replication errors. It requires the MSH2, MSH6,
      MLH1, and PMS2 proteins which comprise the MutSalpha and MutLalpha heterodimers.
      Inactivation of MSH2 or MLH1 in human tumors greatly increases spontaneous
      mutation rates. Oxidation produces many detrimental DNA alterations against which
      cells deploy multiple protective strategies. The Ogg-1 DNA glycosylase initiates
      base excision repair (BER) of 8-oxoguanine (8-oxoG) from 8-oxoG:C pairs. The Myh
      DNA glycosylase removes mismatched adenines incorporated opposite 8-oxoG during
      replication. Subsequent BER generates 8-oxoG:C pairs, a substrate for excision by
      Ogg-1. MTH1-an 8-oxodGTPase which eliminates 8-oxodGTP from the dNTP pool-affords
      additional protection by minimizing 8-oxodGMP incorporation during replication.
      Here we show that the dNTP pool is, nevertheless, an important source of DNA 8
      oxoG and that MMR provides supplementary protection by excising incorporated 8
      oxodGMP. Incorporated 8-oxodGMP contributes significantly to the mutator
      phenotype of MMR-deficient cells. Thus, although BER of 8-oxoG is independent of
      Msh2, both steady-state and H(2)O(2)-induced DNA 8-oxoG levels are higher in Msh2
      defective cells than in their repair-proficient counterparts. Increased
      expression of MTH1 in MMR-defective cells significantly reduces steady-state and
      H(2)O(2)-induced DNA 8-oxoG levels. This reduction dramatically diminishes the
      spontaneous mutation rate of Msh2(-/-) MEFs.

PMID- 12062056
TI  - A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle.
AB  - The role of the PI 3-kinase cascade in regulation of cell growth is well
      established [1]. PKB (protein kinase B) is a key downstream effector of the PI 3
      kinase pathway and is best known for its antiapoptotic effects [2,3] and the role
      it plays in initiation of S phase [4]. Here, we show that PKB activity is high in
      the G2/M phase of the cell cycle in epithelial cells. Inhibition of the PI 3
      kinase pathway in MDCK cells induces apoptosis at the G2/M transition, prevents
      activation of cyclin B-associated kinase, and prohibits entry of the surviving
      cells into mitosis. All of these consequences of the inhibition of PI 3-kinase
      are relieved by expression of a constitutively active form of PKB (caPKB),
      indicating that PKB plays a role in regulation of the G2/M phase. Inhibition of
      PI 3-kinase results in activation of Chk1, whereas caPKB inhibits the ability of
      Chk1 to become activated in response to treatment with hydroxyurea. Preliminary
      data show that PKB phosphorylates the Chk1 polypeptide in vitro on serine 280.
      These results not only implicate PKB activity in transition through the G2/M
      stage of the cell cycle, but they also suggest the existence of crosstalk between
      the PI 3-kinase pathway and the key regulators of the DNA damage checkpoint
      machinery.

PMID- 12062057
TI  - The sister-chromatid cohesion protein ORD is required for chiasma maintenance in
      Drosophila oocytes.
AB  - Accurate chromosome partitioning during cell division requires that cohesion hold
      sister chromatids together until kinetochores correctly attach to spindle
      microtubules. In 1932, Darlington noted that sister-chromatid cohesion distal to
      the site of exchange also could play a vital role in maintaining the association
      of chiasmate homologs during meiosis. Cohesion linking a recombinant chromatid
      with a sister of each homologous pair would resist spindle forces that separate
      kinetochores of homologous chromosomes (see Figure 1). Although centromeric
      cohesion must be retained to ensure proper segregation during meiosis II,
      dissolution of arm cohesion would be required for anaphase I to occur. This
      hypothesis is supported by recent evidence in yeast and C. elegans that separase
      activity is essential for the segregation of recombinant homologs during meiosis
      I. We present evidence that Drosophila oocytes require sister-chromatid cohesion
      to maintain a physical attachment between recombinant chromosomes. Using FISH to
      monitor cohesion directly, we confirm that oocytes lacking ORD activity exhibit
      cohesion defects, consistent with previous genetic results. We also show that
      ord(null) oocytes that have undergone recombination are unable to arrest at
      metaphase I, indicating that chiasmata are unstable in the absence of cohesion.
      Our results support the model that arm cohesion provides a conserved mechanism
      that ensures physical attachment between recombinant homologs until anaphase I.

PMID- 12062058
TI  - Telomere looping permits repression "at a distance" in yeast.
AB  - In yeast, unlike in higher eukaryotes, transcriptional activators and repressors
      do not normally work when bound to DNA at large distances (over 500 base pairs)
      from the gene and, in particular, when positioned downstream of the gene. This
      restriction is relieved for a transcriptional activator if a gene bearing an
      activator binding site is placed near a yeast telomere. The explanation proposed
      is that the folded structure found at the telomere helps appose the DNA-bound
      activator with proteins binding to the promoter so that recruitment of the
      transcriptional machinery can be effected "at a distance". Here, we show that a
      repressor, Tup1, works when tethered to DNA downstream of, and some 1.5-kb from,
      the gene when the construct is placed near a yeast telomere. The effect, observed
      with activated as well as basal transcription, is eliminated by deletion of Sir3.
      These and other results indicate that DNA-tethered Tup1 represses by interacting
      with some component of the transcriptional machinery binding to the promoter, an
      interaction that is facilitated by the preformed loop at the telomere.

PMID- 12062059
TI  - The TBP-inhibitory domain of TAF145 limits the effects of nonclassical
      transcriptional activators.
AB  - Many genes in bacteria and eukaryotes are activated by "regulated recruitment".
      According to that picture, a transcriptional activator binds cooperatively to DNA
      with the transcriptional machinery, and the constitutively active polymerase then
      spontaneously transcribes the gene. An important class of experiments that helped
      develop this model is called the "activator by-pass" experiment. In one version
      of such an experiment, the ordinary activator-transcriptional machinery
      interaction is replaced by a heterologous interaction. For example, fusing any of
      several DNA binding domains to Gal11, a component of the yeast mediator complex,
      creates a powerful activator of genes bearing the corresponding DNA binding
      sites. Here, we describe a simple modification of the yeast transcriptional
      machinery that extends the success of similar experiments involving other
      mediator components. The results reinforce parallels between regulation of
      enzymes involved in transcription and in other cellular processes.

PMID- 12062060
TI  - The ion channel polycystin-2 is required for left-right axis determination in
      mice.
AB  - Generation of laterality depends on a pathway which involves the asymmetrically
      expressed genes nodal, Ebaf, Leftb, and Pitx2. In mouse, node monocilia are
      required upstream of the nodal cascade. In chick and frog, gap junctions are
      essential prior to node/organizer formation. It was hypothesized that
      differential activity of ion channels gives rise to unidirectional transfer
      through gap junctions, resulting in asymmetric gene expression. PKD2, which if
      mutated causes autosomal dominant polycystic kidney disease (ADPKD) in humans,
      encodes the calcium release channel polycystin-2. We have generated a knockout
      allele of Pkd2 in mouse. In addition to malformations described previously,
      homozygous mutant embryos showed right pulmonary isomerism, randomization of
      embryonic turning, heart looping, and abdominal situs. Leftb and nodal were not
      expressed in the left lateral plate mesoderm (LPM), and Ebaf was absent from
      floorplate. Pitx2 was bilaterally expressed in posterior LPM but absent
      anteriorly. Pkd2 was ubiquitously expressed at headfold and early somite stages,
      with higher levels in floorplate and notochord. The embryonic midline, however,
      was present, and normal levels of Foxa2 and shh were expressed, suggesting that
      polycystin-2 acts downstream or in parallel to shh and upstream of the nodal
      cascade.

PMID- 12062061
TI  - Mitotic exit network controls the localization of Cdc14 to the spindle pole body
      in Saccharomyces cerevisiae.
AB  - Budding yeast Cdc14 phosphatase plays essential roles in mitotic exit. Cdc14 is
      sequestered in the nucleolus by its inhibitor Net1/Cfi1 and is only released from
      the nucleolus during anaphase to inactivate mitotic CDK. It is believed that the
      mitotic exit network (MEN) is required for the release of Cdc14 from the
      nucleolus because liberation of Cdc14 by net1/cfi1 mutations bypasses the
      essential role of the MEN. But how the MEN residing at the spindle pole body
      (SPB) controls the association of Cdc14 with Net1/Cfi1 in the nucleolus is not
      yet understood. We found that Cdc14-5GFP was released from the nucleolus in the
      MEN mutants (tem1, cdc15, dbf2, and nud1), but not in the cdc5 cells during early
      anaphase. The Cdc14 liberation from the nucleolus was inhibited by the Mad2
      checkpoint and by the Bub2 checkpoint in a different manner when microtubule
      organization was disrupted. We observed Cdc14-5GFP at the SPB in addition to the
      nucleolus. The SPB localization of Cdc14 was significantly affected by the MEN
      mutations and the bub2 mutation. We conclude that Cdc14 is released from the
      nucleolus at the onset of anaphase in a CDC5-dependent manner and that MEN
      factors possibly regulate Cdc14 release from the SPB.

PMID- 12062062
TI  - A direct interaction between IP(3) receptors and myosin II regulates IP(3)
      signaling in C. elegans.
AB  - Molecular and physiological studies of cells implicate interactions between the
      cytoskeleton and the intracellular calcium signalling machinery as an important
      mechanism for the regulation of calcium signalling. However, little is known
      about the functions of such mechanisms in animals. A key component of the calcium
      signalling network is the intracellular release of calcium in response to the
      production of the second messenger inositol 1,4,5-trisphosphate (IP(3)), mediated
      by the IP(3) receptor (IP(3)R). We show that C. elegans IP(3)Rs, encoded by the
      gene itr-1, interact directly with myosin II. The interactions between two myosin
      proteins, UNC-54 and MYO-1, and ITR-1 were identified in a yeast two-hybrid
      screen and subsequently confirmed in vivo and in vitro. We defined the
      interaction sites on both the IP(3)R and MYO-1. To test the effect of disrupting
      the interaction in vivo we overexpressed interacting fragments of both proteins
      in C. elegans. This decreased the animal's ability to upregulate pharyngeal
      pumping in response to food. This is a known IP(3)-mediated process [15]. Other
      IP(3)-mediated processes, e.g., defecation, were unaffected. Thus it appears that
      interactions between IP(3)Rs and myosin are required for maintaining the
      specificity of IP(3) signalling in C. elegans and probably more generally.

PMID- 12062063
TI  - Producing cells retain and recycle Wingless in Drosophila embryos.
AB  - There is considerable interest in the mechanisms that drive and control the
      spread of morphogens in developing animals. Although much attention is given to
      events occurring after release from expressing cells, release itself could be an
      important modulator of range. Indeed, a dedicated protein, Dispatched, is needed
      to release Hedgehog from the surface of expressing cells. We find that, in
      Drosophila embryos, much Wingless (as well as a GFP-Wingless fusion protein)
      remains tightly associated with secreting cells. Retention occurs both within the
      secretory pathway and at the cell surface and requires functional heparan sulfate
      proteoglycans. As a further means of retention, secreting cells readily
      endocytose Wingless protein that does reach the cell surface. Such endocytosed
      Wingless can in turn be sent back to the cell surface (the first direct
      observation of ligand recycling in live embryos). Recycling may serve to sustain
      high-level signaling in this region of the epidermis.

PMID- 12062064
TI  - Abbey ambitions to celebrate home of genetics.
AB  - A century and a half after the ground-breaking work by Gregor Mendel in
      establishing the foundation of genetics, efforts are under way to develop a
      fitting commemoration of his work at his abbey home in Brno. Nigel Williams
      reports.

PMID- 12062066
TI  - E2F proteins.

PMID- 12062067
TI  - Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk
      mice with polycystic kidney disease.

PMID- 12062068
TI  - Inner space: reference frames.

PMID- 12062070
TI  - Chemosensation: tasting with the tail.
AB  - Animals employ multiple mechanisms to detect the presence and location of
      environmental stimuli. Recent work suggests that Caenorhabditis elegans uses
      chemosensory information provided by spatially distinct sensilla to generate a
      sensory map of its environment and to avoid noxious compounds.

PMID- 12062069
TI  - Planar polarity: photoreceptors on a high fat diet.
AB  - Differential activity of Frizzled in the R3/R4 photo-receptors of Drosophila
      regulates the orientation of ommatidia. New evidence suggests that the cadherins
      Dachsous and Fat act upstream of Frizzled in this process.

PMID- 12062071
TI  - Auxin action: slogging out of the swamp.
AB  - How does auxin affect so many different aspects of plant growth and development?
      Recent evidence from localization of auxin efflux carriers and the effects of
      auxin on degradation of transcription factors has begun to reveal a possible
      mechanism for auxin action.

PMID- 12062072
TI  - Bacterial sporulation: FtsZ rings do the twist.
AB  - Formation of the polar Z ring is a crucial step in the establishment of cellular
      asymmetry during sporulation of Bacillus subtilis. New results suggest that the
      transition from medial to polar Z rings involves a dynamic FtsZ spiral structure
      that may transfer FtsZ from medial to polar sites.

PMID- 12062073
TI  - Neural plasticity: how the eye tells the brain about sound location.
AB  - Recent studies in owls and ferrets seem to have identified the origin and nature
      of the visual signals that shape the development of the auditory space map in the
      midbrain, which ensures that the neural representations of both sensory
      modalities share the same topographic organization.

PMID- 12062074
TI  - Embryonic development: a new SPN on cell fate specification.
AB  - The recent identification and characterization of the Caenorhabditis elegans gene
      spn-4 has shed new light on the mechanisms that link embryonic polarity to the
      specification of cell fates.

PMID- 12062075
TI  - Signal transduction: receptor clusters as information processing arrays.
AB  - The organization of transmembrane receptors into higher-order arrays occurs in
      cells as different as bacteria, lymphocytes and neurons. What are the
      implications of receptor clustering for short-term and long-term signaling
      processes that occur in response to ligand binding?

PMID- 12062076
TI  - Plant K+ transport: not just an uphill struggle.
AB  - Most plant cells can accumulate K+ to concentrations much higher than those in
      the external medium. Recent studies are providing new insights into the relative
      roles of channels and transporters in K+ accumulation. These studies are also
      pointing to specific roles for K+ channels and transporters in polarized
      development.

PMID- 12062077
TI  - RING finger specificity in SCF-driven protein destruction.
AB  - SCF ubiquitin ligases contain an E3 core composed of Skp1, Cul1, a member of the
      Rbx1/Roc1 family of RING finger proteins, and a modular F box protein that
      functions in substrate targeting. Work published in this issue of Developmental
      Cell indicates that distinct Rbx1/Roc1 family members are used to control
      ubiquitination of distinct targets, suggesting that the RING finger subunit may
      contribute to ubiquitination specificity.

PMID- 12062078
TI  - Pioneering work in vertebrate neural development.
AB  - Control of directional axon growth is fundamental to correct wiring in the
      nervous system, and glia are thought to play an important role. New work in the
      zebrafish lateral line shows that glia are not required for axonal pathfinding
      but are required for normal mature nerve organization.

PMID- 12062079
TI  - Morphogen gradients, in theory.
AB  - The idea that morphogen gradients are established by a process of repeated cycles
      of exocytosis and endocytosis-so-called planar transcytosis-has been gaining
      acceptance. This is now challenged by a theoretical approach that experimental
      biologists should not dismiss; diffusive mechanisms of gradient formation may be
      correct after all.

PMID- 12062080
TI  - The undiscovered country: chromosome territories and the organization of
      transcription.
AB  - The interchromosome domain (ICD) model proposes that genes are selectively
      positioned at the surfaces of chromosome territories to facilitate their
      regulation. A paper in the May 13 issue of the Journal of Cell Biology provides
      evidence that supports a reinterpretation of this model.

PMID- 12062082
TI  - Convergent extension: the molecular control of polarized cell movement during
      embryonic development.
AB  - During development, vertebrate embryos undergo dramatic changes in shape. The
      lengthening and narrowing of a field of cells, termed convergent extension,
      contributes to a variety of morphogenetic processes. Focusing on frogs and fish,
      we review the different cellular mechanisms and the well-conserved signaling
      pathways that underlie this process.

PMID- 12062081
TI  - Looking over the edge: a new role for Ena/VASP proteins in lamellipodial
      dynamics.
AB  - How can Ena/VASP proteins promote actin-based movement of the intracellular
      pathogen Listeria or rapid protrusion of lamellipodia but at the same time
      inhibit cell translocation? A report in the May 17(th) issue of Cell now offers a
      possible explanation for this conundrum. Bear et al. report that Ena/VASP
      proteins regulate cell motility by competing with capping proteins to control
      actin filament length and geometry at the leading edge of cells.

PMID- 12062083
TI  - Plasticity, niches, and the use of stem cells.
AB  - Stem cells possess the ability to self-renew and generate multiple cell types of
      the tissues in which they reside. Several studies have reported
      transdifferentiation events between different somatic stem cells. These
      properties have created tremendous excitement about the prospect of using stem
      cells from easily accessible sources for tissue engineering. However, recently,
      the plasticity of stem cells has met with several strong challenges. In this
      meeting review, we will discuss issues surrounding reports of
      transdifferentiation, the molecular mechanisms that govern stem cell states, and
      progress toward putting stem cells to use.

PMID- 12062084
TI  - Loss of nuclear receptor SHP impairs but does not eliminate negative feedback
      regulation of bile acid synthesis.
AB  - The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid
      synthesis was examined. Loss of SHP in mice caused abnormal accumulation and
      increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and
      CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids
      induced liver damage and restored feedback regulation. A synthetic agonist of the
      nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction
      of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression.
      We conclude that input from three negative regulatory pathways controls bile acid
      synthesis. One is mediated by SHP, and two are SHP independent and invoked by
      liver damage and changes in bile acid pool size.

PMID- 12062085
TI  - Redundant pathways for negative feedback regulation of bile acid production.
AB  - The orphan nuclear hormone receptor SHP has been proposed to have a key role in
      the negative feedback regulation of bile acid production. Consistent with this,
      mice lacking the SHP gene exhibit mild defects in bile acid homeostasis and fail
      to repress cholesterol 7-alpha-hydroxylase expression in response to a specific
      agonist for the bile acid receptor FXR. However, this repression is retained in
      SHP null mice fed bile acids, demonstrating the existence of compensatory
      repression pathways of bile acid signaling. We provide evidence for two such
      pathways, based on activation of the xenobiotic receptor PXR or the c-Jun N
      terminal kinase JNK. We conclude that redundant mechanisms regulate this critical
      aspect of cholesterol homeostasis.

PMID- 12062086
TI  - Csk, a critical link of g protein signals to actin cytoskeletal reorganization.
AB  - Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but
      the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient
      mouse embryonic fibroblast cells, G protein (Gbetagamma, Galpha(12), Galpha(13),
      and Galpha(q))-induced, and G protein-coupled receptor-induced, actin stress
      fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent
      cells restored the G protein-induced actin stress fiber formation. Chemical
      rescue experiments with catalytic mutants of Csk demonstrated that the catalytic
      activity of Csk was required for this process. Furthermore, we uncovered that
      Gbetagamma can both translocate Csk to the plasma membrane and directly increase
      Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk
      plays a critical role in mediating G protein signals to actin cytoskeletal
      reorganization.

PMID- 12062087
TI  - Regulated SUMOylation and ubiquitination of DdMEK1 is required for proper
      chemotaxis.
AB  - MEK1, which is required for aggregation and chemotaxis in Dictyostelium, is
      rapidly and transiently SUMOylated in response to chemoattractant stimulation.
      SUMOylation is required for MEK1's function and its translocation from the
      nucleus to the cytosol and cortex, including the leading edge of chemotaxing
      cells. MEK1 in which the site of SUMOylation is mutated is retained in the
      nucleus and does not complement the mek1 null phenotype. Constitutively active
      MEK1 is cytosolic and is constitutively SUMOylated, whereas the corresponding
      nonactivatable MEK1 is not SUMOylated and nuclear. MEK1 is also ubiquitinated in
      response to signaling. A MEK1-interacting, ubiquitin E3 ligase RING domain
      containing protein controls nuclear localization and MEK1 ubiquitination. These
      studies provide a pathway regulating the localization and function of MEK1.

PMID- 12062088
TI  - Drosophila Roc1a encodes a RING-H2 protein with a unique function in processing
      the Hh signal transducer Ci by the SCF E3 ubiquitin ligase.
AB  - Substrate specificity of SCF E3 ubiquitin ligases is thought to be determined by
      the F box protein subunit. Another component of SCF complexes is provided by
      members of the Roc1/Rbx1/Hrt1 gene family, which encode RING-H2 proteins.
      Drosophila contains three members of this gene family. We show that Roc1a mutant
      cells fail to proliferate. Further, while the F box protein Slimb is required for
      Cubitus interruptus (Ci) and Armadillo/beta-catenin (Arm) proteolysis, Roc1a
      mutant cells hyperaccumulate Ci but not Arm. This suggests that Slimb and Roc1a
      function in the same SCF complex to target Ci but that a different RING-H2
      protein acts with Slimb to target Arm. Consequently, the identity of the Roc
      subunit may contribute to the selection of substrates by metazoan SCF complexes.

PMID- 12062089
TI  - Smad10 is required for formation of the frog nervous system.
AB  - Before the nervous system establishes its complex array of cell types and
      connections, multipotent cells are instructed to adopt a neural fate and an
      anterior-posterior pattern is established. In this report, we show that Smad10, a
      member of the Smad family of intracellular transducers of TGFbeta signaling, is
      required for formation of the nervous system. In addition, two types of molecules
      proposed as key to neural induction and patterning, bone morphogenetic protein
      (BMP) antagonists and fibroblast growth factor (FGF), require Smad10 for these
      activities. These data suggest that Smad10 may be a central mediator of the
      development of the frog nervous system.

PMID- 12062090
TI  - Do morphogen gradients arise by diffusion?
AB  - Many patterns of cell and tissue organization are specified during development by
      gradients of morphogens, substances that assign different cell fates at different
      concentrations. Gradients form by morphogen transport from a localized site, but
      whether this occurs by simple diffusion or by more elaborate mechanisms is
      unclear. We attempt to resolve this controversy by analyzing recent data in ways
      that appropriately capture the complexity of systems in which transport, receptor
      interaction, endo- and exocytosis, and degradation occur together. We find that
      diffusive mechanisms of morphogen transport are much more plausible-and
      nondiffusive mechanisms much less plausible-than has generally been argued.
      Moreover, we show that a class of experiments, endocytic blockade, thought to
      effectively distinguish between diffusive and nondiffusive transport models
      actually fails to draw useful distinctions.

PMID- 12062091
TI  - Short-range cell interactions and cell survival in the Drosophila wing.
AB  - During development of multicellular organisms, cells are often eliminated by
      apoptosis if they fail to receive appropriate signals from their surroundings.
      Here, we report on short-range cell interactions that support cell survival in
      the Drosophila wing imaginal disc. We present evidence showing that cells
      incorrectly specified for their position undergo apoptosis because they fail to
      express specific proteins that are found on surrounding cells, including the LRR
      transmembrane proteins Capricious and Tartan. Interestingly, only the
      extracellular domains of Capricious and Tartan are required, suggesting that a
      bidirectional process of cell communication is involved in triggering apoptosis.
      We also present evidence showing that activation of the Notch signal transduction
      pathway is involved in triggering apoptosis of cells misspecified for their
      dorsal-ventral position.

PMID- 12062092
TI  - An evolutionarily conserved mediator of plant disease resistance gene function is
      required for normal Arabidopsis development.
AB  - Plants recognize many pathogens through the action of a diverse family of
      proteins called disease resistance (R) genes. The Arabidopsis R gene RPM1 encodes
      resistance to specific Pseudomonas syringae strains. We describe an RPM1
      interacting protein that is an ortholog of TIP49a, previously shown to interact
      with the TATA binding protein (TBP) complex and to modulate c-myc- and beta
      catenin-mediated signaling in animals. Reduction of Arabidopsis TIP49a (AtTIP49a)
      mRNA levels results in measurable increases of two R-dependent responses without
      constitutively activating defense responses, suggesting that AtTIP49a can act as
      a negative regulator of at least some R functions. Further, AtTIP49a is essential
      for both sporophyte and female gametophyte viability. Thus, regulators of R
      function overlap with essential modulators of plant development.

PMID- 12062093
TI  - miwi, a murine homolog of piwi, encodes a cytoplasmic protein essential for
      spermatogenesis.
AB  - The piwi family genes are crucial for stem cell self-renewal, RNA silencing, and
      translational regulation in diverse organisms. However, their function in mammals
      remains unexplored. Here we report the cloning of a murine piwi gene (miwi)
      essential for spermatogenesis. miwi encodes a cytoplasmic protein specifically
      expressed in spermatocytes and spermatids. miwi(null) mice display spermatogenic
      arrest at the beginning of the round spermatid stage, resembling the phenotype of
      CREM, a master regulator of spermiogenesis. Furthermore, mRNAs of ACT (activator
      of CREM in testis) and CREM target genes are downregulated in miwi(null) testes.
      Whereas MIWI and CREM do not regulate each other's expression, MIWI complexes
      with mRNAs of ACT and CREM target genes. Hence, MIWI may control spermiogenesis
      by regulating the stability of these mRNAs.

PMID- 12062094
TI  - The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves
      Huntingtin phosphorylation by Akt.
AB  - In the search for neuroprotective factors in Huntington's disease, we found that
      insulin growth factor 1 via activation of the serine/threonine kinase Akt/PKB is
      able to inhibit neuronal death specifically induced by mutant huntingtin
      containing an expanded polyglutamine stretch. The IGF-1/Akt pathway has a dual
      effect on huntingtin-induced toxicity, since activation of this pathway also
      results in a decrease in the formation of intranuclear inclusions of mutant
      huntingtin. We demonstrate that huntingtin is a substrate of Akt and that
      phosphorylation of huntingtin by Akt is crucial to mediate the neuroprotective
      effects of IGF-1. Finally, we show that Akt is altered in Huntington's disease
      patients. Taken together, these results support a potential role of the Akt
      pathway in Huntington's disease.

PMID- 12062095
TI  - Plant immunity and film Noir: what gumshoe detectives can teach us about plant
      pathogen interactions.
AB  - Plant cells practice constant vigilance using resistance (R) proteins to monitor
      pathogenic processes. Three papers published recently in Cell and one in Science
      provide support for a model in which plant cells set up surveillance of signal
      transduction pathways, preparing to destroy the cell if any untoward fiddling
      with cellular physiology is detected. The demonstration of three separate
      examples of such a system suggests that it is broadly used and should provoke a
      reexamination of microbial pathogenesis in animal cells to look for similar
      mechanisms.

PMID- 12062096
TI  - PI 3-kinases and PTEN: how opposites chemoattract.
AB  - Phosphatidylinositol lipids, such as PI(4,5)P2 and PI(3,4,5)P3, are key mediators
      in diverse intracellular signaling pathways. Two recent reports examine how the
      metabolism of these lipids by phosphatidylinositol 3-kinases and the PTEN 3
      phosphoinositide phosphatase may coordinate G protein coupled signaling pathways
      during eukaryotic chemotaxis.

PMID- 12062097
TI  - At the center of eukaryotic life.
AB  - The ribosomal RNA genes encode the enzymatic scaffold of the ribosome and thereby
      perform perhaps the most basic of all housekeeping functions. However, recent
      data suggests that they might also control important aspects of cell behavior.

PMID- 12062099
TI  - Chromatin boundaries in budding yeast: the nuclear pore connection.
AB  - Chromatin boundary activities (BAs) were identified in Saccharomyces cerevisiae
      by genetic screening. Such BAs bound to sites flanking a reporter gene establish
      a nonsilenced domain within the silent mating-type locus HML. Interestingly,
      various proteins involved in nuclear-cytoplasmic traffic, such as exportins
      Cse1p, Mex67p, and Los1p, exhibit a robust BA. Genetic studies,
      immunolocalization, live imaging, and chromatin immunoprecipitation experiments
      show that these transport proteins block spreading of heterochromatin by physical
      tethering of the HML locus to the Nup2p receptor of the nuclear pore complex.
      Genetic deletion of NUP2 abolishes the BA of all transport proteins, while direct
      targeting of Nup2p to the bracketing DNA elements restores activity. The data
      demonstrate that physical tethering of genomic loci to the NPC can dramatically
      alter their epigenetic activity.

PMID- 12062100
TI  - Cid13 is a cytoplasmic poly(A) polymerase that regulates ribonucleotide reductase
      mRNA.
AB  - Fission yeast Cid13 and budding yeast Trf4/5 are members of a newly identified
      nucleotidyltransferase family conserved from yeast to man. Trf4/5 are thought to
      be essential DNA polymerases. We report that Cid13 is a poly(A) polymerase.
      Unlike conventional poly(A) polymerases, which act in the nucleus and
      indiscriminately polyadenylate all mRNA, Cid13 is a cytoplasmic enzyme that
      specifically targets suc22 mRNA that encodes a subunit of ribonucleotide
      reductase (RNR). cid13 mutants have reduced dNTP pools and are sensitive to
      hydroxyurea, an RNR inhibitor. We propose that Cid13 defines a cytoplasmic form
      of poly(A) polymerase important for DNA replication and genome maintenance.

PMID- 12062101
TI  - A Yersinia effector and a Pseudomonas avirulence protein define a family of
      cysteine proteases functioning in bacterial pathogenesis.
AB  - A Yersinia effector known as YopT and a Pseudomonas avirulence protein known as
      AvrPphB define a family of 19 proteins involved in bacterial pathogenesis. We
      show that both YopT and AvrPphB are cysteine proteases, and their proteolytic
      activities are dependent upon the invariant C/H/D residues conserved in the
      entire YopT family. YopT cleaves the posttranslationally modified Rho GTPases
      near their carboxyl termini, releasing them from the membrane. This leads to the
      disruption of actin cytoskeleton in host cells. The proteolytic activity of
      AvrPphB is essential for autoproteolytic cleavage of an AvrPphB precursor as well
      as for eliciting the hypersensitive response in plants. These findings provide
      new insights into mechanisms of animal and plant pathogenesis.

PMID- 12062102
TI  - Two distinct Pseudomonas effector proteins interact with the Pto kinase and
      activate plant immunity.
AB  - The Pto serine/threonine kinase of tomato confers resistance to speck disease by
      recognizing strains of Pseudomonas syringae that express the protein AvrPto. Pto
      and AvrPto physically interact, and this interaction is required for activation
      of host resistance. We identified a second Pseudomonas protein, AvrPtoB, that
      interacts specifically with Pto and is widely distributed among plant pathogens.
      AvrPtoB is delivered into the plant cell by the bacterial type III secretion
      system, and it elicits Pto-specific defenses. AvrPtoB has little overall sequence
      similarity with AvrPto. However, AvrPto amino acids, which are required for
      interaction with Pto, are present in AvrPtoB and required for its interaction
      with Pto. Thus, two distinct bacterial effectors activate plant immunity by
      interacting with the same host protein kinase through a similar structural
      mechanism.

PMID- 12062103
TI  - Tumor suppressor PTEN mediates sensing of chemoattractant gradients.
AB  - Shallow gradients of chemoattractants, sensed by G protein-linked signaling
      pathways, elicit localized binding of PH domains specific for PI(3,4,5)P3 at
      sites on the membrane where rearrangements of the cytoskeleton and pseudopod
      extension occur. Disruption of the PI 3-phosphatase, PTEN, in Dictyostelium
      discoideum dramatically prolonged and broadened the PH domain relocation and
      actin polymerization responses, causing the cells lacking PTEN to follow a
      circuitous route toward the attractant. Exogenously expressed PTEN-GFP localized
      to the surface membrane at the rear of the cell. Membrane localization required a
      putative PI(4,5)P2 binding motif and was required for chemotaxis. These results
      suggest that specific phosphoinositides direct actin polymerization to the cell's
      leading edge and regulation of PTEN through a feedback loop plays a critical role
      in gradient sensing and directional migration.

PMID- 12062104
TI  - Spatial and temporal regulation of 3-phosphoinositides by PI 3-kinase and PTEN
      mediates chemotaxis.
AB  - We have investigated the mechanisms of leading edge formation in chemotaxing
      Dictyostelium cells. We demonstrate that while phosphatidylinositol 3-kinase
      (PI3K) transiently translocates to the plasma membrane in response to
      chemoattractant stimulation and to the leading edge in chemotaxing cells, PTEN, a
      negative regulator of PI3K pathways, exhibits a reciprocal pattern of
      localization. By uniformly localizing PI3K along the plasma membrane, we show
      that chemotaxis pathways are activated along the lateral sides of cells and PI3K
      can initiate pseudopod formation, providing evidence for a direct instructional
      role of PI3K in leading edge formation. These findings provide evidence that
      differential subcellular localization and activation of PI3K and PTEN is required
      for proper chemotaxis.

PMID- 12062106
TI  - HEN-1, a secretory protein with an LDL receptor motif, regulates sensory
      integration and learning in Caenorhabditis elegans.
AB  - Animals sense many environmental stimuli simultaneously and integrate various
      sensory signals within the nervous system both to generate proper behavioral
      responses and also to form relevant memories. HEN-1, a secretory protein with an
      LDL receptor motif, regulates such processes in Caenorhabditis elegans. The hen-1
      mutants show defects in the integration of two sensory signals and in behavioral
      plasticity by paired stimuli, although their sensation capability seems to be
      identical to that of the wild-type. The HEN-1 protein is expressed in two pairs
      of neurons, but expression in other neurons is sufficient for wild-type behavior.
      In addition, expression of HEN-1 at the adult stage is sufficient. Thus, HEN-1
      regulates sensory processing non-cell-autonomously in the mature neuronal
      circuit.

PMID- 12062105
TI  - Recruitment of stem and progenitor cells from the bone marrow niche requires MMP
      9 mediated release of kit-ligand.
AB  - Stem cells within the bone marrow (BM) exist in a quiescent state or are
      instructed to differentiate and mobilize to circulation following specific
      signals. Matrix metalloproteinase-9 (MMP-9), induced in BM cells, releases
      soluble Kit-ligand (sKitL), permitting the transfer of endothelial and
      hematopoietic stem cells (HSCs) from the quiescent to proliferative niche. BM
      ablation induces SDF-1, which upregulates MMP-9 expression, and causes shedding
      of sKitL and recruitment of c-Kit+ stem/progenitors. In MMP-9-/- mice, release of
      sKitL and HSC motility are impaired, resulting in failure of hematopoietic
      recovery and increased mortality, while exogenous sKitL restores hematopoiesis
      and survival after BM ablation. Release of sKitL by MMP-9 enables BM repopulating
      cells to translocate to a permissive vascular niche favoring differentiation and
      reconstitution of the stem/progenitor cell pool.

PMID- 12062107
TI  - Sex-specific deployment of FGF signaling in Drosophila recruits mesodermal cells
      into the male genital imaginal disc.
AB  - A central issue in developmental biology is how the deployment of generic
      signaling proteins produces diverse specific outcomes. We show that Drosophila
      FGF is used, only in males, to recruit mesodermal cells expressing its receptor
      to become part of the genital imaginal disc. Male-specific deployment of FGF
      signaling is controlled by the sex determination regulatory gene doublesex. The
      recruited mesodermal cells become epithelial and differentiate into parts of the
      internal genitalia. Our results provide exceptions to two basic tenets of
      imaginal disc biology-that imaginal disc cells are derived from the embryonic
      ectoderm and belong to either an anterior or posterior compartment. The recruited
      mesodermal cells migrate into the disc late in development and are neither
      anterior nor posterior.

PMID- 12062108
TI  - Extraction and analysis of microcystins RR and LR in cyanobacteria using a cyano
      cartridge.
AB  - A new method for the extraction of microcystins RR and LR in cyanobacteria was
      developed using a cyano cartridge. Lyophilized cells (100 mg) were extracted with
      5% (v/v) acetic acid. The extract was centrifuged and then the supernatant was
      applied to a CN cartridge. The cartridge that contained microcystins was rinsed
      with 5 ml of water and 5 ml of 0.5 M acetic acid, followed by 5 ml of 5%
      acetonitrile in water. Microcystins were finally eluted from the CN cartridge
      with 70% acetonitrile in water and were determined by HPLC. Better recoveries and
      chromatograms were observed than with ODS cartridges.

PMID- 12062109
TI  - Adduct formation in DNA as a basis for the establishment of mutational spectra
      using a novel polymerase termination reaction: an adjunct to the ames test?

PMID- 12062110
TI  - Microwave-assisted rapid characterization of lipase selectivities.
AB  - A rapid screening procedure for characterization of lipase selectivities using
      microwaves was developed. The rate of reaction of various commercial lipases
      (porcine pancreas, Mucor miehei, Candida rugosa, Pseudomonas cepacia) as well as
      lipases from laboratory isolates-Bacillus stearothermophilus and Burkholderia
      cepacia RGP-10 for triolein hydrolysis was 7- to 12-fold higher in a microwave
      oven as compared to that by pH stat. The esterification of sucrose/methanol and
      ascorbic acid with different fatty acids was also achieved within 30 s in a
      microwave using porcine pancreas, B. stearothermophilus SB-1 and B. cepacia RGP
      10 lipases. The relative rates and selectivity of the lipases both for hydrolytic
      and synthesis reactions remains unaltered. However, the rate of reaction was
      dynamically enhanced when exposed to microwaves. Microwave-assisted enzyme
      catalysis can become an attractive procedure for rapid characterization of large
      number of enzyme samples and substrates, which otherwise is a cumbersome and time
      consuming exercise.

PMID- 12062111
TI  - Detection of insulin-regulated GLUT4-translocation by the insertion of a protein
      C epitope in L6 myoblasts.
AB  - Insulin stimulates glucose transport by translocation of the membrane glucose
      transporter GLUT4 from intracellular vesicles to the plasma membrane. GLUT4 is
      highly expressed in adipose tissue and skeletal muscle. We have constructed a
      cDNA containing the human GLUT4 inserted by a 12 amino acid protein C epitope in
      the first extracellular (exofacial) domain of the human GLUT4 (GLUT4-PC). Stable
      expression of GLUT4-PC in L6 myoblasts (L6-GLUT4-PC) was confirmed in
      immunofluorescence using monoclonal antibodies against protein C. The protein C
      staining yielded labeling in perinuclear vesicles strongly co-localizing with
      GLUT4 detected with antibodies directed against the endofacial part of GLUT4. The
      L6-GLUT4-PC cells were further characterized in a direct cell-based enzyme-linked
      immunosorbent assay by the use of beta-galactosidase. Cell surface binding of
      monoclonal protein C antibodies was detected with beta-galactosidase-conjugated
      secondary antibodies and chlorophenolred-beta-D-galactopyranoside (CPRG) as
      substrate in 2% paraformaldehyde fixed cells. In this assay, stimulation with
      insulin created a rapidly detectable recruitment of GLUT4-PC to the cell surface.
      This cell-based enzyme-linked immunosorbent GLUT4 assay was shown to be
      comparable with that of previously reported radioactive assays.

PMID- 12062112
TI  - An improved method for isolation of anti-viper venom antibodies from chicken egg
      yolk.
AB  - The production of antibodies and its purification from mammalian blood has been
      found low yielding and laborious. Therefore, anti snake venom antibodies for
      therapeutic use is obtained mostly as polyvalent whole serum or partially
      purified polyvalent immunoglobulin. The side effects of anti snake venom (ASV)
      therapy are mainly serum sickness and renal failure, which may be reduced by
      using sufficiently pure antibodies. Therefore, we have standardized a simple
      method for production of purified antivenom. Here, we present the development of
      polyclonal antibodies against viper venom in hens and its isolation from the egg
      yolk of immunized birds. We have modified the reported methods of purification of
      immunoglobulin from egg yolk, and thus yielded 90% purity of the protein. The
      modified method involves only two steps, such as removal of lipids from the
      diluted egg yolk by a freeze-thaw cycle and centrifugation, followed by gel
      filtration on Biogel P-150. The advantages are that the process is very simple,
      and from one egg, 100+/-20 mg of pure immunoglobulin is obtained. The antibodies
      are present in the egg for up to 100 days after the immunization. Thus, using
      small amounts of venom, a large quantity of the immunoglobulin is obtained in a
      sufficiently pure form. The antigen binding ability of the pure antibody is found
      good by the Ouchterlony's double diffusion experiment.

PMID- 12062113
TI  - Enzymatic assay of gamma-cystathionase activity using pyruvate oxidase-peroxidase
      sequential reaction.
AB  - A highly sensitive method has been developed for the determination of gamma
      cystathionase (EC. 4.4.1.1.) activity in rat tissues using beta-chloro-L-alanine
      as a substrate. This method is based on colorimetry for the determination of
      pyruvate produced from beta-chloro-L-alanine with the beta-elimination catalyzed
      by gamma-cystathionase, coupling a color enzymatic reaction with pyruvate oxidase
      and peroxidase. The absorbance increases with the oxidized color of a leuco dye,
      N-(carboxymethylamino)-4,4'-bis (dimethylamino)-diphenylamine at 727 nm is
      proportional to the gamma-cystathionase activity. The present method is more
      sensitive and more rapid than the usual methods and does not require troublesome
      steps such as centrifugation. The calibration curve is linear up to 1.6 microg of
      partially purified enzyme (100 U/l). Comparison with the usual method with L
      homoserine as a substrate gave good correlation (r=0.990). The present method was
      applied to the determination of gamma-cystathionase activity in adult male rat
      tissues. The mean activities in liver and kidney were 8.03 and 3.91 U/g wet
      weight (n=10), respectively.

PMID- 12062115
TI  - Temperature modulation of DHPLC analysis for detection of coexisting
      constitutional and mosaic sequence variants in TSC2.
AB  - Somatic mosaicism is a frequent phenomenon in Mendelian disorders that exhibit a
      high proportion of new mutations. However, mutant alleles present at low
      frequency may escape detection. We have previously shown that denaturing high
      performance liquid chromatography (DHPLC) at the recommended melt temperature can
      detect TSC1 and TSC2 mutations in tuberous sclerosis patients with low-level
      somatic mosaicism, even when direct sequencing cannot identify the causative
      lesion. Here, we report the use of temperature modulation in DHPLC analysis to
      facilitate the robust detection of a mosaic mutation, N1643K, in the presence of
      a coexisting constitutional polymorphism.

PMID- 12062114
TI  - A cloth strip bioreactor with immobilized glucoamylase.
AB  - Glucoamylase was immobilized on polyethylenimine (PEI)-coated cotton cloth by
      adsorption followed by cross-linking with 0.2% glutaraldehyde in the presence of
      starch. Optimal adsorption of the enzyme was seen when cloth treated with 2% PEI
      was contacted with the enzyme for 50 min. pH and temperature optima profiles were
      not changed appreciably on immobilization. However, the bound enzyme exhibited a
      higher thermal stability. The enzyme-bound cloth strips were used in a specially
      designed bioreactor for the continuous hydrolysis of starch. The reactor could be
      operated for over 21 days retaining about 70% of the original activity. An
      operational temperature of 45 degrees C was found to be optimal.

PMID- 12062116
TI  - Fluorescence polarization discriminates green fluorescent protein from
      interfering autofluorescence in a microplate assay for genotoxicity.
AB  - An unconventional use for the polarization optics, associated with a variety of
      commercially available fluorescence microplate readers, is reported. This novel
      application has allowed the discrimination of green fluorescent protein (GFP)
      fluorescence in genetically modified yeast cells from interfering autofluorescent
      species. The method exploits the unusually high fluorescence anisotropy of GFP
      compared to smaller fluorophores and autofluorescent species. The principle was
      successfully applied to resolve the induced GFP signal from that of
      autofluorescent test compounds, in an assay for genotoxic species. The use of
      fluorescence polarization enabled both proflavin and methapyrilene to be
      identified as genotoxic agents in the yeast assay. This would not have been
      possible using conventional fluorescence alone since these compounds were found
      to be intensely autofluorescent at the same wavelength as GFP and thus
      effectively mask the GFP signal.

PMID- 12062117
TI  - A procedure for analysis of stopped-flow transients for protein-ligand
      association.
AB  - A method for extracting kinetic and optical parameters from progress curves for
      protein-ligand association, obtained by stopped-flow experiments, is described.
      The method is limited to one-step and two-step association kinetics, but it
      allows concentration of protein and offset of the signals to be adjustable
      parameters during an interactive non-linear least-squares fitting procedure. The
      method is tested on simulated pseudo-experimental data and applied to progress
      curves obtained in a stopped-flow spectrofluorimeter, for association of the
      translation initiation factor eIF4E with 7-methyl-GDP, an analog of 5'-end of
      mRNA.

PMID- 12062118
TI  - Addition of Polybrene improves stability of organophosphate hydrolase immobilized
      in poly(vinyl alcohol) cryogel carrier.
AB  - Organophosphate hydrolase, covalently attached to the beads of poly(vinyl
      alcohol) cryogel in the presence of Polybrene, was fivefold more stable in 15%
      (v/v) ethanol solution than the free enzyme. Immobilized biocatalyst, prepared
      with an addition of Polybrene, retained a half of its initial activity in 50%
      (v/v) aqueous ethanol solution, 90% of activity during 10 working cycles of
      Paraoxon hydrolysis and 85% of activity after storage in the 50 mM CHES buffer
      (pH 9.0) at room temperature for 2 months.

PMID- 12062119
TI  - DNA-fiber EPR study of the orientation of Cu(II) complexes of 1,10-phenanthroline
      and its derivatives bound to DNA: mono(phenanthroline)-copper(II) and its ternary
      complexes with amino acids.
AB  - The orientation of mono(1,10-phenanthroline)copper(II), [Cu(phen)]2+, and the
      ternary complexes with amino acids, [Cu(phen)X(aa)]n+, where X(aa) stands for an
      alpha-amino acid, has been investigated by electron paramagnetic resonance (EPR)
      spectra of the complexes on DNA fibers. It has been revealed that these complexes
      bind to DNA with several different binding modes. The observation of a species
      whose g axis is almost parallel to the DNA double helical axis has suggested that
      the phenanthroline moiety intercalates to DNA. An absence of the intercalated
      species for the corresponding 2,2'-bipyridine complex has shown that the three
      fused aromatic rings in phenanthroline are critical for the intercalative binding
      of the complexes. The intercalative binding was promoted by 5,6-dimethyl groups
      on the phenanthroline ring, whereas it was disturbed by 2,9-dimethyl groups,
      indicating that the planarity of the coordination sphere is important for the
      intercalative binding. In all cases, the amount of the non-intercalated species
      was larger than that of the intercalated one. The amino acids in the ternary
      complexes of glycine, leucine, serine, threonine, cysteine, methionine, and
      asparagine were partly substituted with some coordinating groups in DNA, whereas
      the ternary complexes of lysine, arginine, and glutamine remained intact on DNA.

PMID- 12062120
TI  - Synthesis and characterization of three new Cu(II)-dipeptide complexes.
AB  - Three new copper(II) complexes of stoichiometry [Cu(L-dipeptide)].nH(2)O,
      containing as ligands the dipeptides L-alanine-L-isoleucine, L-alanine-L
      threonine and L-alanine-L-tyrosine were prepared. They were characterized by
      single crystal X-ray diffractometry, and electronic and infrared spectroscopy. In
      all cases, the Cu(II) cation has essentially the same elongated square pyramidal
      coordination, being equatorially cis coordinated by a N(2)O(2) arrangement of
      ligand atoms and axially by a carbonyl oxygen atom. The compounds show rather
      similar polymeric structures which resemble those recently reported for the
      [Cu(ala-val)] and [Cu(ala-phe)] complexes. The electronic and infrared spectra
      are briefly discussed on the basis of the structural peculiarities of the
      complexes. Superoxide dismutase (SOD)-like activity was also tested for the
      compounds.

PMID- 12062121
TI  - Spectroscopic and potentiometric study of the SOD mimic system copper(II)/acetyl
      L-histidylglycyl-L-histidylglycine.
AB  - Stoichiometry, stability constants and solution structures of the copper(II)
      complexes of the N-acetylated tetrapeptide HisGlyHisGly were determined in
      aqueous solution in the pH range 2-11. The potentiometric and spectroscopic data
      (UV-Vis, CD, EPR and Raman scattering) show that acetylation of the amino
      terminal group induces drastic changes in the coordination properties of AcHGHG
      compared to HGHG. The N3 atoms of the histidine side chains are the first
      anchoring sites of the copper(II) ion. At pH 4.7 and 5.6 both the imidazole rings
      cooperate in the formation of a 2N equatorial set, while, at higher pH values, 3N
      and 4N complexes are formed through the coordination of peptide N- atoms. The
      logbeta values of the copper complexes of AcHGHG are by far lower than those of
      the corresponding species in the parent CuII-HGHG system.

PMID- 12062122
TI  - Oxidative cleavage of DNA by a dipyridoquinoxaline copper(II) complex in the
      presence of ascorbic acid.
AB  - Complex [Cu(dpq)(2)(H(2)O)](ClO(4))(2).H(2)O (1), where dpq is dipyrido-[3,2
      D:2',3'-f]-quinoxaline, has been prepared by reacting copper(II) perchlorate
      hexahydrate with dpq in methanol and structurally characterized. The complex
      crystallizes in the triclinic space group P-1 with the unit cell parameters
      a=8.646(2) A, b=12.290(5) A, c=14.283(4) A, alpha=94.01(2) degrees, beta=91.69(2)
      degrees,gamma=101.60 (3) degrees, V=1481.7(8) A(3) and Z=2. The structure,
      refined to R=0.0505 and R(w)=0.1441 for 5212 reflections with I>2sigma (I) using
      440 parameters, shows the presence of a CuN(4)O chromophore in an axially
      compressed distorted trigonal-bipyramidal structure. The Cu-N distances lie in
      the range 1.969(3)-2.103(3) A. The Cu-OH(2) distance is 2.145(3) A. The complex
      is one-electron paramagnetic and exhibits a visible spectral d-d band at 718 nm
      in MeCN. It shows a quasi-reversible cyclic voltammetric response at 0.091 V
      (DeltaE(p)=229 mV) at 50 mV s(-1) in MeCN-0.1 M TBAP for the Cu(II)/Cu(I) couple.
      In 50 mM Tris-HCl/0.1 M KCl buffer-DMF mixture (1:4 v/v, pH 7.2), the couple
      appears at 0.089 V versus SCE. The complex undergoes facile reduction with sodium
      ascorbate in an aqueous DMF mixture (4:1 v/v) to form an unstable brown Cu(I)
      species (lambda(max)=440 nm, epsilon=7480 M(-1) cm(-1)) which converts to 1 on
      exposure to air giving a turnover frequency of ca. 400. Binding studies revealed
      that 1 is an efficient binder to calf thymus DNA. Complex 1 on reaction with
      supercoiled (SC) DNA in presence of ascorbic acid in a 50 mM Tris-HCl/50 mM NaCl
      buffer (pH 7.2) shows nuclease activity which is 4.5 times greater than that of
      the phen analogue.

PMID- 12062123
TI  - Glutathione induces cellular resistance against cationic dinuclear platinum
      anticancer drugs.
AB  - The sulfur-containing tripeptide glutathione (GSH) is one of the most abundant
      molecules in cells. Elevated levels of GSH render some types of cancer cells
      resistant against well-known platinum anti-cancer drugs such as cisplatin and
      carboplatin. Platinum complexes are often very reactive towards the cysteine
      residue of GSH, which detoxifies these compounds by a rapid binding mechanism.
      Clearly, this resistance mechanism poses a severe obstacle to any new platinum
      drugs designed to overcome cisplatin resistance. In the present study the
      cytotoxicity of dinuclear platinum compounds of the 1,1/t,t type, as developed by
      Farrell, is determined in human ovarium A2780 cells and in the cisplatin
      resistant cell line A2780cisR, which possesses elevated levels of GSH. Further,
      the effect of depletion of GSH levels by L-buthionine-S,R-sulfoximine (L-BSO) in
      A2780cisR was investigated. The experiments show that detoxification by GSH is an
      effective resistance mechanism against dinuclear platinum compounds. However, the
      dinuclear complexes are less sensitive towards detoxification compared to
      cisplatin. This is probably because of the rapid binding of dinuclear cationic
      complexes to DNA. Compared to cisplatin, the rapid binding to DNA reduces the
      time during which the drug molecules are exposed to GSH in the cytosol. The
      reaction of a representative dinuclear compound with glutathione (pH 7, 37
      degrees C) was studied in detail by 195Pt NMR. The dinuclear complex BBR3005
      ([trans-PtCl(2)(NH(3))(2)(mu-H(2)N(CH(2))(6)NH(2))](2+), abbreviated as 1,1/t,t
      n=6), follows different pathways in the reaction with GSH, depending on the molar
      ratio of the reactants. When reacted in stoichiometric amounts (1:1), first a
      chloride on each platinum is replaced by a sulfur, forming a PtN(3)S product at 
      2977 ppm. After 2-3 h, this intermediate reacts further to form a sulfur-bridged
      N(3)Pt-S-PtN(3) species as the main product at -2811 ppm. When BBR3005 is reacted
      with GSH in a ratio of 1:4, the sulfur-bridged species is not observed. Instead,
      the final product is trans-Pt(GS)(2)(NH(3))(2) (at -3215 ppm); the same product
      appears if GSH is reacted with trans-PtCl(2)(NH(3))(2). Apparently, GSH first
      replaces the chlorides and subsequently degrades the dinuclear compound by
      replacement of the diaminealkyl linker.

PMID- 12062124
TI  - Synthesis, cytotoxicity, antibacterial and antitumor activity of platinum(II)
      complexes of 3-aminocyclohexanespiro-5-hydantoin.
AB  - New platinum(II) complexes of 3-aminocyclohexanespiro-5-hydantoin (achsh) were
      prepared and characterized. Ab initio calculation of the structure and the
      measurements of IR and NMR spectra of [Pt(NH(3))(achsh)Cl(2)] were also
      performed. Quantum-chemical and spectroscopic studies indicated a cis-square
      planar structure with a hydantoin ligand coordinated via the NH(2) group. The
      complexes were evaluated for in vitro cytotoxicity in murine erythroleukemia
      (MEL) cells, clone F4N, as well as for in vivo antitumor activity toward murine
      L1210 leukemia. The complexes exerted significantly lower in vitro and in vivo
      toxicities compared with those of cisplatin (cis-diamminedichloroplatinum(II),
      DDP). The complex [Pt(NH(3))(achsh)Cl(2)] exhibited antitumor activity against
      L1210 leukemia, comparable to that of cisplatin, resulting at a dose of 72 mg/kg
      in a %T/C (increased survival time) of 191%. This complex, as well as cisplatin,
      induced apoptosis in F4N cells, and exerted antibacterial activity as assessed in
      10 bacterial strains.

PMID- 12062125
TI  - Aqueous and solid complexes of iron(III) with hyaluronic acid. Potentiometric
      titrations and infrared spectroscopy studies.
AB  - The coordination of iron(III) ion to hyaluronic acid (Hyal) in aqueous solutions
      and solid state was accomplished by potentiometric titrations and infrared
      spectroscopy. The potentiometric titration studies provided the binding constants
      for the complexes found in the systems and the speciation of these species
      according to the variation of pH values. The complexes found presented a
      complexing ability through both the chelating moieties of Hyal (via the N
      glucosamine and D-glucoronic acid), showing no special preference for either one
      while in solid state, but when in aqueous solution the complexation via the N
      glucosamine moiety was the preferred, forming two complexed species, ML and ML(2)
      (log K(ML)=8.2 and log K(ML2)=7.9). The presence of a mu-oxo complex via the D
      glucoronic acid was also detected in both aqueous (log K=6.7) and solid states
      via the N-glucosamine and D-glucoronic acid simultaneously linked to two Hyal
      chains. A structure for this latter complex was suggested. The results indicated
      that these complexes could be used in eliminating the excess iron(III) in living
      organisms.

PMID- 12062126
TI  - Solution equilibrium studies on metal complexes of 2,3-dihydroxy-phenylalanine
      hydroxamic acid (Dopaha) and models: catecholate versus hydroxamate coordination
      in iron(III)-, aluminium(III)- and molybdenum(VI)-Dopaha complexes.
AB  - Equilibrium results based on pH potentiometric, spectrophotometric and (1)H NMR
      measurements for the complexes of Fe(III), Al(III) and Mo(VI) with 2,3-dihydroxy
      phenylalanine-hydroxamic acid (Dopaha) as well as for binary model systems
      Fe(III)-, Al(III)-, Mo(VI)-acetohydroxamic acid (Aha), -alpha-alaninehydroxamic
      acid (alpha-Alaha) and -1,2-dihydroxy-3,5-benzene-disulphonate (Tiron) and
      ternary model systems Fe(III)-, Al(III)-, Mo(VI)-Tiron-Aha, are summarized in
      this paper. The amine-type coordination mode is not detectable with these metal
      ions at all. Precipitation occurs at pH <5.5 with Fe(III) and Al(III) even at a
      Dopaha-to-metal ion ratio of 10:1. Hydroxamate-type coordination was demonstrated
      with both metals below the pH range of precipitation but, after dissolution,
      catecholate-type coordination was exclusively found. The hydroxamate-type
      coordination mode occurs only in the very acidic pH range for Mo(VI) complexes
      and the crossover from hydroxamate to catecholate binding occurs at pH >3. A
      ligand-bridged dinuclear species, [(MoO(2))(2)(Dopaha)(2)](2+), involving mixed
      type (catecholate and hydroxamate) coordination modes is formed in the pH range
      2.5-5.5. [MoO(2)A(2)H(2)], with catecholate-type coordination, forms above pH 3.
      On increasing the pH further, deprotonation of the coordinated Dopaha and
      hydrolytic processes result in the formation of catecholate-coordinated
      [MoO(3)AH] and [MoO(3)A]. MoO(4)(2-) and free Dopaha exist above pH 10.

PMID- 12062127
TI  - The interaction of 5-fluoroorotic acid with transition metals: synthesis and
      characterisation of Ni(II), Cu(II) and Zn(II) complexes.
AB  - 5-Fluoroorotic acid (H(3)FOro) is a potent inhibitor for some metalloproteins
      such as dihydroorotase and dihydroorotate dehydrogenase and for thymidylate
      synthase (nonmetalloprotein) in the human malaria parasite Plasmodium falciparum.
      To study the coordination chemistry of H(3)Foro, the ammonium salt
      [NH(4)(+)][H(2)FOro(-)].1H(2)O (1) and the first coordination compounds of
      H(3)FOro with transition metals [Ni(HFOro(2-))(H(2)O)(4)].1H(2)O (2), [Cu(HFOro(2
      ))(NH(3))(H(2)O)](n) (3) and [Cu(3)(FOro(3-))(2)(NH(3))(6)(H(2)O)(2)] (4) have
      been synthesised and characterised by single-crystal X-ray diffraction, IR
      spectroscopy and by thermogravimetry. Three different coordination modes of 5
      fluoroorotic acid have been established. In all cases the ligand is chelated to
      the metal via an amido-nitrogen and a carboxylate-oxygen but for (3), there is
      also a carboxylate oxygen from another HFOro(2-) ligand resulting in a polymeric
      structure and for (4), the second amido-nitrogen in the ororotic acid ring
      coordinates to give a trinuclear complex. The metal coordination polyhedra are
      octahedral in (2), square-pyramidal in (3) and square-planar and approximately
      square-pyramidal in (4). An octahedral coordination geometry including a
      N(1)/O(61)-chelating HFOro(2-) ligand with four aqua ligands is proposed for the
      Zn complex [Zn(HFOro(2-)) (H(2)O)(4)].0.5H(2)O (5), based on IR and
      thermogravimetric data. Extensive hydrogen bonded networks and some ring-ring
      stacking interactions are observed in each of the structures.

PMID- 12062128
TI  - Pd(II)- and Pt(II)-cimetidine complexes. Crystal structure of trans-[Pt(N,S
      cimetidine)(2)]Cl(2)(*)12H(2)O.
AB  - The influence of cimetidine on patients under cisplatin treatment for cancer is
      controversial. It has moderate or no effects on several types of cancer and its
      effects on the nephrotoxicity induced by cisplatin are uncertain. To examine the
      binding properties and antiproliferative effects of the known anticancer noble
      metals, cimetidine (cim) was complexed to platinum(II) and palladium(II). The
      crystal structure of the Pt-cim compound shows two molecules of cimetidine
      coordinated to the metal through thioether sulfur and imidazolic nitrogen whereas
      spectroscopic studies in solution for Pd-cim reveal that the ratio of the metal
      to cimetidine is 1:1 with identical coordination environments. To determine the
      antitumor activity of the drugs, the interaction of the metallic complexes and
      free cimetidine with DNA was assessed. Their cytotoxic activity was compared with
      that of cisplatin.

PMID- 12062130
TI  - Kinetic study of catalytic CO(2) hydration by water-soluble model compound of
      carbonic anhydrase and anion inhibition effect on CO(2) hydration.
AB  - A kinetic study of CO(2) hydration was carried out using the water-soluble zinc
      model complex with water-soluble nitrilotris(2-benzimidazolylmethyl-6-sulfonate)
      L1S, [L1SZn(OH(2))](-), mimicking the active site of carbonic anhydrase, in the
      presence and absence of anion inhibitors NCS(-) and Cl(-). The obtained rate
      constants k(cat) for CO(2) hydration were 5.9x10(2), 1. 7x10(3), and 3.1x10(3) M(
      1) s(-1) at 5, 10, and 15 degrees C, respectively: the k(cat)=ca. 10(4) M(-1) s(
      1) extrapolated towards 25 degrees C has been the largest among the reported
      k(cat) using zinc model complexes for carbonic anhydrase. It was also revealed
      that NCS(-), Cl(-) and acetazolamide play a role of inhibitors by the decrease of
      k(cat): 7x10(2) and 2x10(3) M(-1) s(-1) for NCS(-) and Cl(-) at 15 degrees C,
      respectively. The sequence of their magnitudes in k(cat) is Cl(-) approximately
      acetazolamide>NCS(-), where the sequence Cl(-)>NCS(-) is confirmed for native
      carbonic anhydrase. The difference of k(cat) or k(obs) between NCS(-) and Cl(-)
      resulted from that between the stability constants K(st)=2x10(3) for
      [L1SZn(NCS)](2-) and 1x10(2) M(-1) for [L1SZnCl](2-) in D(2)O: for water
      insoluble tris(2-benzimidazolylmethyl)amine L1, K(st)=1.8x10(4) for [L1Zn(NCS)](2
      ) and 1.5x10(3) M(-1) for [L1ZnCl](2-)in CD(3)CN/D(2)O (50% v/v). The crystal
      structure of anion-binding zinc model complexes [L1Zn(OH(2))](0.5)[L1ZnCl](0.5)
      (ClO(4))(1.5) 1(0.5)2(0.5)(ClO(4))(1.5) was revealed by X-ray crystallography.
      The geometry around Zn(2+) in 1 and 2 was tetrahedrally coordinated by three
      benzimidazolyl nitrogen atoms and one oxygen atom of H(2)O, or Cl(-).

PMID- 12062129
TI  - Study on the amount of binding of anti-tumor metal complexes to different target
      sites of dGMP using trans-[en(2)Os(eta2-H(2))(CF(3)SO(3))](CF(3)SO(3)) in a
      competitive mode.
AB  - In order to investigate the binding sites and the amount of binding of a number
      of anti-tumor metal complexes (cisplatin, Cp(2)TiCl(2) and (CH(3))(2)SnCl(2)) to
      target molecule DNA mononucleotides in aqueous solution, a 1H NMR recognition
      probe, trans-[en(2)Os(eta2-H(2))(CF(3)SO(3))](CF(3)SO(3)), was used in a
      competitive mode. The minimum percentages of binding of anti-tumor metal
      complexes to different sites of dGMP were also determined.

PMID- 12062131
TI  - Release of NO by a nitrosyl complex upon activation by the mitochondrial reducing
      power.
AB  - The reaction of trans-[Ru(NH(3))(4)P(OEt)(3)NO](3+) and mitochondria was
      investigated through differential pulse polarography and fluorimetry. The
      nitrosyl complex undergoes one-electron reduction centered on the NO ligand site.
      The reaction between the mitochondrial reductor and trans
      [Ru(NH(3))(4)P(OEt)(3)NO](3+) exhibits a second order specific rate constant
      calculated as k=2 x 10(1) M(-1) s(-1). The reduced species, trans
      [Ru(NH(3))(4)P(OEt)(3)NO](2+), quickly releases NO, yielding trans
      [Ru(NH(3))(4)P(OEt)(3)H(2)O](2+). The low toxicities of both trans
      [Ru(NH(3))(4)P(OEt)(3)(NO)](2+) and trans-[Ru(NH(3))(4)P(OEt)(3)H(2)O](2+) and
      its ability to release NO after reductive activation in a biological medium make
      the nitrosyl compound a useful model of a hypotensive drug.

PMID- 12062132
TI  - The fate of the biomimetic cation triaqua-mu-oxohexapropionatotrichromium(III) in
      rats.
AB  - The synthetic biomimetic triaqua-mu-oxohexapropionatotrichromium(III) nitrate
      when given intravenously to rats lowers fasting blood plasma triglycerides and
      cholesterol concentrations; thus, the cation has the potential to serve as a
      therapeutic agent. Its ability to function in vivo presumably is dependent on its
      ability to mimic the action of the natural, bioactive, chromium-binding
      oligopeptide chromodulin in stimulating insulin receptor kinase activity.
      Consequently, the cation should be incorporated into insulin-sensitive cells
      intact. Thus, the fate of the 51Cr-labeled complex during the first 24 h after
      injection in tissues, blood, urine, and feces was followed. The complex appears
      to be readily incorporated into tissues and cells. In hepatocytes, the cation is
      efficiently transported into microsomes where its concentration reaches a maximum
      in approximately 2 h.

PMID- 12062133
TI  - Organometallic complexes with biological molecules. XVII. Triorganotin(IV)
      complexes with amoxicillin and ampicillin.
AB  - Novel triorganotin(IV) complexes of two beta-lactamic antibiotics, 6-[D-(-)-beta
      amino-p-hydroxyphenyl-acetamido]penicillin (=amoxicillin) and 6-[D-(-)-alpha
      aminobenzyl]penicillin (=ampicillin), have been synthesized and investigated both
      in solid and solution states. The complexes corresponded to the general formula
      R(3)Sn(IV)antib*H(2)O (R=Me, n-Bu, Ph; antib=amox=amoxicillinate or
      amp=ampicillinate). Structural investigations about configuration in the solid
      state have been carried out by interpreting experimental IR and 119Sn Mossbauer
      data. In particular, IR results suggested polymeric structures both for
      R(3)Sn(IV)amox.H(2)O and R(3)Sn(IV)amp*H(2)O. Moreover, both antibiotics appear
      to behave as monoanionic bidentate ligands coordinating the tin(IV) atom through
      ester-type carboxylate, as well as through the beta-lactamic carbonyl. Evidence
      that in none of these compounds water molecules were involved in coordination,
      was provided by thermogravimetric investigations. On the basis of 119Sn Mossbauer
      spectroscopy it can be inferred that tin(IV) was pentacoordinate in all of the
      complexes in the solid state, showing an equatorial R(3)Sn(IV) trigonal
      bipyramidal (tbp) configuration. The nature of the complexes in solution state
      was investigated by using 1H and 13C nuclear magnetic resonance (NMR)
      spectroscopy, while an 119Sn spectrum was obtained for n-Bu(3)Sn(IV)amp*H(2)O.
      Although 1H- and 13C-NMR measurements suggested that in dimethyl sulfoxide (DMSO)
      d(6) solution the polymeric structure collapsed, due to a solvolysis process of
      the beta-lactamic carbonyl bonding to the organometallic moiety, the complexes
      have been shown to maintain the same trigonal bipyramidal configuration at
      tin(IV) atom by the coordination of a DMSO molecule. Cytotoxic activity of these
      novel semisynthetic antibiotic derivatives has been tested towards spermatocyte
      chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia) using two
      different chromosome-staining techniques such as Giemsa and CMA(3). The
      occurrence of typical colchicinized-like (c-like) mitoses on slides obtained from
      animals exposed to organotin compounds, directly confirmed the high mitotic
      spindle-inhibiting potency of these chemicals. In addition, by comparative
      analysis of spermatocyte chromosomes from untreated specimens (negative controls)
      and specimens treated with the triorganotin(IV) complexes, structural damages
      such as 'achromatic lesions' and 'chromosome breakages' have been identified.

PMID- 12062134
TI  - Preparation and cell growth inhibitory activity of [PtR(2)L(2)]
      (R=polyfluorophenyl, L(2)=diene, cyclohexane-1,2-diamine (chxn) or cis-(dimethyl
      sulfoxide)(2)) and the X-ray crystal structure of [Pt(C(6)F(5))(2)(cis-chxn)].
AB  - A range of [PtR(2)(chxn)] (R=C(6)F(5), o-HC(6)F(4), p-HC(6)F(4), p-MeOC(6)F(4) or
      3,5-H(2)C(6)F(3); chxn=cyclohexane-1,2-diamine) and cis-[PtR(2)(dmso)(2)]
      (R=C(6)F(5), p-HC(6)F(4) or p-MeOC(6)F(4); dmso=dimethyl sulfoxide) complexes
      have been prepared from the corresponding [PtR(2)(diene)] (diene=cis,cis
      cycloocta-1,5-diene (cod), hexa-1,5-diene (hex), norbornadiene (nbd) or
      dicyclopentadiene (dcy)) derivatives and have been spectroscopically
      characterized. A representative crystal structure of [Pt(C(6)F(5))(2)(cis-chxn)]
      was determined and shows a slightly distorted square planar geometry for platinum
      with chxn virtually perpendicular to the coordination plane. The biological
      activity against L1210 and L1210/DDP cell lines of these compounds together with
      the behaviour of other organoplatinum complexes, [PtR(2)L(2)] (L(2)=ethane-1,2
      diamine (en) or cis-(NH(3))(2)) have been determined. Despite the use of
      relatively inert fluorocarbon anions as leaving groups, moderate-high cell growth
      inhibitory activity is observed. None of the fluorocarbon complexes displayed any
      cross resistance with cisplatin.

PMID- 12062135
TI  - Cardiac rehabilitation I: review of psychosocial factors.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability for
      women and men. There are gender differences in recovery from coronary events,
      which may be due physiological, sociodemographic, or psychosocial factors.
      Cardiac rehabilitation programs have beneficial effects on coronary recovery. The
      following presents a review of the literature from MedLine (1997-2001) and
      PsychInfo (1984-2001) on gender differences in participation in cardiac
      rehabilitation programs, with a focus on depression, anxiety, self-efficacy and
      social support. A critical analysis of gaps in the literature as well as areas
      for future research are presented.

PMID- 12062136
TI  - Cardiac rehabilitation II: referral and participation.
AB  - Cardiovascular disease (CVD) is the leading cause of death and disability for
      women and men. Substantial health risks continue following ischemic coronary
      events (ICEs), but secondary prevention efforts, including cardiac rehabilitation
      (CR), have beneficial effects on both early and late mortality and morbidity.
      This prospective study examined the relationship among psychosocial factors and
      CR referral and participation patterns in 906 (586 men, 320 women) patients from
      the coronary intensive care unit (CICU) over the course of six months. Only 30%
      of participants were referred to CR programs, with significantly fewer women
      being referred. A logistic regression analysis was used to determine whether
      depression, anxiety, self-efficacy, or social support predicted CR participation
      six months following an ICE, while controlling for sociodemographic factors.
      Results show that higher family income, greater anxiety symptomatology, and
      higher self-efficacy were significantly predictive of CR participation at six
      months. Implications for women's recovery from an ICE are discussed.

PMID- 12062137
TI  - Specific phobia of illness in the community.
AB  - This study evaluated the prevalence, risk factors and morbidity associated with
      specific phobia of illness. Subjects were from a random, community telephone
      survey of 500 persons age 40 to 65 who lived in Johnson County, Iowa, USA. Forty
      three subjects reported that illness fears substantially bothered them personally
      or affected their medical care, work, or social life. Twenty-one of these
      subjects could be contacted and agreed to a semistructured interview designed to
      diagnose specific phobia of illness and screen for other common psychiatric
      disorders. Based on the interview, 10 subjects met the criteria for specific
      phobia of illness, 10 for major depressive disorder, 5 for obsessive-compulsive
      disorder, 5 for generalized anxiety disorder, 4 for hypochondriasis, 4 for panic
      disorder and 4 for specific phobia other than illness. Assuming subjects not
      interviewed were similar to subjects who were, the community prevalence of
      specific phobia of illness is 4.0%. Among the 10 subjects with specific phobia of
      illness, 7 had prior negative experiences with illness and 8 had comorbid Axis I
      disorders. The phobia interfered with medical care as well as social functioning
      for many subjects. These results suggest a prevalence rate and risk factors that
      will be useful for additional studies of illness phobia.

PMID- 12062138
TI  - Effect of smoking, alcohol, and depression on the quality of life of head and
      neck cancer patients.
AB  - This pilot study examined the relationship between smoking, alcohol intake,
      depressive symptoms and quality of life (QoL) in head and neck cancer patients. A
      questionnaire on smoking, alcohol, depressive symptoms and QoL was distributed to
      head and neck cancer patients (N=81). Over one-third (35%) of the respondents had
      smoked within the last 6 months, 46% had drunk alcohol within the last 6 months
      and 44% screened positive for significant depressive symptoms. About one-third
      (32%) of smokers were interested in smoking cessation services and 37% of
      patients with depressive symptoms were interested in depression services.
      However, only 9% of those who drank alcohol expressed interest in alcohol
      services. Smoking was negatively associated with five scales of the SF-36V
      including Physical Functioning, General Health, Vitality, Social Functioning, and
      Role-Emotional Health. Depressive symptoms were negatively associated with all
      eight scales on the SF-36V and all four scales of the Head and Neck Quality of
      Life instrument. Surprisingly, alcohol was not found to be associated with any of
      the QoL scales. While smoking, alcohol intake and depression may be episodically
      treated, standardized protocols and aggressive intervention strategies for
      systematically addressing these highly prevalent disorders are needed in this
      population.

PMID- 12062139
TI  - Treating panic disorder in primary care: a collaborative care intervention.
AB  - Efficacy research indicates the success of cognitive behavioral treatment and
      medication treatment for panic disorder with or without agoraphobia. However,
      research findings to date possess limited generalizability beyond specialty
      mental health settings. We present a model for collaborative care treatment for
      panic disorder in the primary care setting that combines cognitive behavioral
      therapy and medications, and involves a behavioral health specialist,
      psychiatrist, and primary care physician. Educational aids that are aimed to
      educate and activate patients to participate as partners in their care are
      provided. We outline the ways in which the standard treatment was modified, in
      light of the nature of the sample and setting, such as fewer sessions and
      management of comorbidity. Also, we provide evidence for acceptability of this
      intervention to primary care physicians and patients. This description is
      intended to lay the groundwork for continued research efforts in the extension of
      efficacious treatments into primary care settings.

PMID- 12062140
TI  - Predictability of the one-year course of depression and generalized anxiety in
      primary care.
AB  - Several predictors of the course of depression and generalized anxiety have been
      identified. Whether these predictors provide a solid basis for primary care
      physicians (PCPs) to give an accurate prognosis remains unclear. A parallel study
      showed modest agreement between PCP prognosis and observed course (kappa< or =
      0.21). It is the aim of the present study to establish the extent to which the
      one-year course of depression and generalized anxiety in primary care is in fact
      predictable. Predictability is operationalized as the combined predictive power
      of major prognostic factors identified in the literature. We identified 269 cases
      of ICD-10 depression and 134 of generalized anxiety among consecutive PCP
      attenders. For these patients a statistical model was built that provided optimal
      predictions of the one-year course of the disorder, based on the prognostic
      factors discerned. The predictions were compared with the actual course observed.
      Reasonable agreement (kappa = 0.37 for depression, kappa = 0.35 for anxiety) and
      good association (gamma = 0.66 for depression, gamma=0.67 for anxiety) were found
      between predicted and observed course. Nevertheless, the combined predictive
      power of the prognostic factors remains limited. A realistic evaluation of the
      accuracy of the PCP prognosis should take this limited predictability into
      account.

PMID- 12062141
TI  - Factitious disorders and pathological self-harm in a hospital population: an
      interdisciplinary challenge.
AB  - Factitious disorder, Munchausen's Syndrome, and deliberate self-harm have
      recently been conceptualized as different facets of self-destructive behavior. A
      descriptive typological classification has been presented by Willenberg et al.,
      but has not yet been tested with a clinical sample. The instrument distinguishes
      between direct self-harm (e.g., self-inflicted wounds), self-induced disease
      (e.g., factitious fever), and indirect self-harm delegated to medical staff
      (e.g., repeated operations occasioned by feigned symptoms). All patients referred
      to the psychosomatic-psychotherapeutic liaison-consultation service or to the
      outpatients' department within 14 months (n = 995) and all patients discharged
      from in-patient psychosomatic-psychotherapeutic treatment within 2 months (n =
      62) were assessed. Expert instruction and supervision were provided for the
      diagnosticians. The assessment was continued for a subsequent year, without
      special supervision (n = 1,058). Self-destructive behaviors were diagnosed in
      7.5% of the cases in the first sample, with certainty (59.5%) or on suspicion
      (40.5%). In the subsequent sample without supervision, the rate reduced to 3.6%.
      Referrals had come from almost all clinical departments, including the emergency
      unit (26%), surgery, internal intensive care, endocrinology (9.5% each),
      neurology, infectiology, nephrology (7.1% each), dermatology, gastro-enterology,
      cardiology (4.8% each) and surgical intensive care (2.4%). The occurrence of
      pathological self-destructive phenomena is underrated when using only the ICD
      criteria. The rate is influenced by diagnostic attention.

PMID- 12062142
TI  - The amplification of somatic symptoms in upper respiratory tract infections.
AB  - To assess the cultural differences in the role of somatosensory amplification in
      Japan and North America, we re-examined the role of psychological amplification
      of objective physical symptoms, as measured by the Somatosensory Amplification
      Scale (SSAS), in 82 Japanese patients with upper-respiratory tract infections.
      Anxiety and depression were measured with the Hospital Anxiety and Depression
      Scale (HADS). We determined the association among continuous variables using the
      Spearman correlation coefficient. Next, we used multiple regression analysis and
      selected all symptoms as independent variables. The SSAS was significantly
      associated with all somatic symptoms. It was also closely related to discomfort,
      but the SSAS was not significantly correlated with either anxiety or depression.
      All somatic symptoms were not significantly correlated with the objective
      physical findings. Multiple regression analyses indicated that amplification by
      SSAS was a statistically significant predictor of the patient's somatic symptoms
      and discomfort. The objective findings did not significantly predict the
      patient's symptoms. Our study provides some empirical evidence regarding
      psychological amplification of objective physical symptoms, as measured by SSAS,
      in Japanese patients with upper-respiratory tract infections. Our findings
      suggest that there is no difference in the role of amplification of bodily
      sensations between Japanese and North Americans.

PMID- 12062143
TI  - Understanding the psychodynamics of non-adherence to medical treatment in persons
      with HIV infection.
AB  - We present this medical-psychiatric case discussion to illustrate the
      psychodynamic aspects of nonadherence in a woman with AIDS. Our patient sustained
      severe, repeated abandonment and brutal emotional, physical and sexual trauma
      throughout her early and later childhood and adult life. Her care was
      considerably complicated by the sequelae of trauma including difficulty with
      trust and posttraumatic stress disorder. The additional problem of HIV dementia
      compounded the patient's nonadherence to treatment. We present a
      multidisciplinary biopsychosocial approach that enabled the patient to engage in
      both medical and psychiatric care.

PMID- 12062144
TI  - Effect of treatment of panic disorder in patients with frequent ICD discharges: a
      pilot study.
AB  - Anxiety and depression are common in patients receiving an implantable
      cardioverter defibrillator (ICD). An association between the number of ICD
      discharges and mood disturbances has been found. We performed a pilot study in
      ICD patients with frequent ICD shocks having a comorbid diagnosis of panic
      disorder with agoraphobia and depression, in which we treated them with a
      combination of a selective serotonin reuptake inhibitor (SSRI) and a behavior
      program. We hypothesized that this intervention would result in a decrease of
      ventricular premature beats or arrhythmias and possibly in a reduction of number
      of shocks. Four of 5 patients treated with such a combination therapy experienced
      no discharge of the ICD during a 6 month follow-up. The total number of
      ventricular premature beats decreased significantly after treatment. There was
      also clear psychiatric improvement. These results warrant larger scale studies on
      the pathophysiological mechanisms as well as treatment issues.

PMID- 12062145
TI  - Identity shifts in temporal lobe epilepsy.

PMID- 12062146
TI  - A bird's eye view: biological categorization and reasoning within and across
      cultures.
AB  - Many psychological studies of categorization and reasoning use undergraduates to
      make claims about human conceptualization. Generalizability of findings to other
      populations is often assumed but rarely tested. Even when comparative studies are
      conducted, it may be challenging to interpret differences. As a partial remedy,
      in the present studies we adopt a 'triangulation strategy' to evaluate the ways
      expertise and culturally different belief systems can lead to different ways of
      conceptualizing the biological world. We use three groups (US bird experts, US
      undergraduates, and ordinary Itza' Maya) and two sets of birds (North American
      and Central American). Categorization tasks show considerable similarity among
      the three groups' taxonomic sorts, but also systematic differences. Notably, US
      expert categorization is more similar to Itza' than to US novice categorization.
      The differences are magnified on inductive reasoning tasks where only
      undergraduates show patterns of judgment that are largely consistent with current
      models of category-based taxonomic inference. The Maya commonly employ causal and
      ecological reasoning rather than taxonomic reasoning. Experts use a mixture of
      strategies (including causal and ecological reasoning), only some of which
      current models explain. US and Itza' informants differed markedly when reasoning
      about passerines (songbirds), reflecting the somewhat different role that
      songbirds play in the two cultures. The results call into question the importance
      of similarity-based notions of typicality and central tendency in natural
      categorization and reasoning. These findings also show that relative expertise
      leads to a convergence of thought that transcends cultural boundaries and shared
      experiences.

PMID- 12062148
TI  - Using uh and um in spontaneous speaking.
AB  - The proposal examined here is that speakers use uh and um to announce that they
      are initiating what they expect to be a minor (uh), or major (um), delay in
      speaking. Speakers can use these announcements in turn to implicate, for example,
      that they are searching for a word, are deciding what to say next, want to keep
      the floor, or want to cede the floor. Evidence for the proposal comes from
      several large corpora of spontaneous speech. The evidence shows that speakers
      monitor their speech plans for upcoming delays worthy of comment. When they
      discover such a delay, they formulate where and how to suspend speaking, which
      item to produce (uh or um), whether to attach it as a clitic onto the previous
      word (as in "and-uh"), and whether to prolong it. The argument is that uh and um
      are conventional English words, and speakers plan for, formulate, and produce
      them just as they would any word.

PMID- 12062147
TI  - Structural constraints in the perception of English stop-sonorant clusters.
AB  - Native-language phonemes combined in a non-native way can be misperceived so as
      to conform to native phonotactics, e.g. English listeners are biased to hear
      syllable-initial [tr] rather than the illegal [tl] (Perception and Psychophysics
      34 (1983) 338; Perception and Psychophysics 60 (1998) 941). What sort of
      linguistic knowledge causes phonotactic perceptual bias? Two classes of models
      were compared: unit models, which attribute bias to the listener's differing
      experience of each cluster (such as their different frequencies), and structure
      models, which use abstract phonological generalizations (such as a ban on
      [coronal][coronal] sequences). Listeners (N=16 in each experiment) judged
      synthetic 6 x 6 arrays of stop-sonorant clusters in which both consonants were
      ambiguous. The effect of the stop judgment on the log odds ratio of the sonorant
      judgment was assessed separately for each stimulus token to provide a stimulus
      independent measure of bias. Experiment 1 compared perceptual bias against the
      onsets [bw] and [dl], which violate different structural constraints but are both
      of zero frequency. Experiment 2 compared bias against [dl] in CCV and VCCV
      contexts, to investigate the interaction of syllabification with segmentism and
      to rule out a compensation-for-coarticulation account of Experiment 1. Results of
      both experiments favor the structure models (supported by NSF).

PMID- 12062149
TI  - Looking without seeing the background change: electrophysiological correlates of
      change detection versus change blindness.
AB  - Two experiments document that conceptual knowledge influences 3-year-olds'
      extension of novel words. In Experiment 1, when objects were described as having
      conceptual properties typical of artifacts, children extended novel labels for
      these objects on the basis of shape alone. When the very same objects were
      described as having conceptual properties typical of animate kinds, children
      extended novel labels for these objects on the basis of both shape and texture.
      Moreover, providing a salient perceptual cue (Experiment 2) did not interfere
      with children's reliance on conceptual information in extending novel words: when
      an object with eyes was labeled with a novel word in the context of a story
      describing the object as an artifact, children extended the label on the basis of
      shape alone (i.e. as though the object were an artifact). These results, which
      challenge directly the position that 'dumb attentional mechanisms' can account
      for word learning, stand as evidence for the central role of conceptual
      information in mapping words to meaning.

PMID- 12062150
TI  - Word learning is 'smart': evidence that conceptual information affects
      preschoolers' extension of novel words.
AB  - We examined electrophysiological correlates of conscious change detection versus
      change blindness for equivalent displays. Observers had to detect any changes,
      across a visual interruption, between a pair of successive displays. Each display
      comprised grey circles on a background of alternate black and white stripes.
      Foreground changes arose when light-grey circles turned dark-grey and vice-versa.
      Physically stronger background changes arose when all black stripes turned white
      and vice-versa. Despite their physical strength, background changes were
      undetected unless attention was directed to them, whereas foreground changes were
      invariably seen. Event-related potentials revealed that the P300 component was
      suppressed for unseen background changes, as compared with the same changes when
      seen. This effect arose first over frontal sites, and then spread to parietal
      sites. These results extend recent fMRI findings that fronto-parietal activation
      is associated with conscious visual change detection, to reveal the timing of
      these neural correlates.

PMID- 12062151
TI  - DNA damage, histological changes and DNA repair in larval Japanese medaka
      (Oryzias latipes) exposed to ultraviolet-B radiation.
AB  - Cyclobutane dimer formation, photorepair capability and histological damage were
      compared among four differently pigmented strains of larval Japanese medaka
      (Oryzias latipes) to determine whether pigmentation modifies the level of UV-B
      radiation (290-320 nm) inducible damage in these fish. One-day post-hatch medaka
      were exposed to one of several UV-B fluence rates with or without
      photoreactivating light for 5 days for 7 h per day. Their DNA was extracted for
      analysis by ELISA for cyclobutane pyrimidine dimers or the larvae were processed
      for histological examination. At the higher UV-B fluence rates tested, wild-type
      melanophore-containing medaka formed significantly more dimers than at least one
      of the other strains tested. Wild-type medaka also showed significantly less
      photorepair capability than the white melanophore-lacking medaka. The wild-type
      larvae had significantly more necrosis than the orange-red melanophore-lacking
      larvae at the lower UV-B fluence rate tested and at the higher fluence rate used,
      the wild-type medaka also exhibited significantly more necrosis than the white
      melanophore-lacking larvae. Of the 19 medaka observed with cellular hyperplasia,
      six were wild-type. These six individual larvae showed the greatest degree of
      cellular hyperplasia. Cellular hyperplasia appeared to be greatest at the lowest
      UV-B fluence rate used. The presence of melanophores in the wild-type medaka may
      have contributed to an increased level of tissue damage in this strain when
      compared to the other strains.

PMID- 12062152
TI  - Metabolism of pyrene by the polychaetes Nereis diversicolor and Arenicola marina.
AB  - Absorption and elimination of [(14)C-4,5,9,10]pyrene and production of water
      insoluble and water-soluble pyrene metabolites by the polychaetes Nereis
      diversicolor and Arenicola marina were studied. Both polychaete species were
      capable of rapidly accumulating and eliminating pyrene. Steady state
      concentrations of pyrene were established in both polychaete species within 5
      days of exposure to contaminated sediments, with A. marina having 5-10 times
      higher bioaccumulation factors than N. diversicolor. Both water-soluble and water
      insoluble metabolites were detected in tissues of N. diversicolor and A. marina.
      After transferring worms to uncontaminated sediment, about 50% of the body burden
      of parent pyrene was excreted within 1.5 days, with elimination in A. marina
      being faster than in N. diversicolor. The only identified water-insoluble
      metabolite produced by N. diversicolor was 1-hydroxypyrene. Pyrene metabolites
      were present in A. marina, but could not be identified. Long- and short-term
      absorption experiments showed an increasing production of water-soluble
      metabolites over time in the lugworm, which strongly suggests the presence of a
      PAH metabolising system in A. marina.

PMID- 12062153
TI  - Effect of humic acids on speciation and toxicity of copper to Paracentrotus
      lividus larvae in seawater.
AB  - The effects of humic acid (HA) on the toxicity of copper to sea urchin
      Paracentrotus lividus larvae were studied in chemically defined seawater. Square
      Wave Anodic Stripping Voltammetry (SWASV) was employed to study the complexation
      of copper in seawater medium. A simple complexation model assuming one ligand
      type and a 1:1 reaction stoichiometry successfully explained the inverse
      titration experiments. A conditional stability constant of 6.53+/-0.05 and a
      complexating capacity of 230+/-7 micromol Cu/g HA were obtained. Sea urchin
      bioassay tests with two endpoints, embryogenesis success and larval growth were
      carried out in order to study the toxicity of dissolved copper in both the
      presence and absence of HA. The toxicity data obtained fitted well into a
      logistic model, and the high sensitivity of both endpoints (EC(50) were 41.1
      microg Cu/l and 32.9 microg Cu/l, respectively) encourages their use for
      biomonitoring. The HA had a clearly protective effect, reducing the toxicity of
      Cu to the sea urchin larvae. The labile copper, rather than the total copper
      concentrations, explained the toxicity of the Cu-HA solutions, and the Cu-HA
      complexes appeared as non-toxic forms. These results are in agreement with the
      Free Ion Activity Model, because the labile Cu concentrations in this buffered
      and chemically defined medium covary with the free ion activity of the Cu,
      validating the model to naturally occurring HA in the marine environment.

PMID- 12062154
TI  - Seasonal variations in condition and liver metal concentrations of yellow perch
      (Perca flavescens) from a metal-contaminated environment.
AB  - The relationships between liver metal (Cu, Zn and Ni) concentration and physical
      condition of yellow perch (Perca flavescens) were compared in fish sampled in
      five northeastern Ontario Lakes in the spring and seven lakes in the fall of
      1997. These lakes represented a wide range of metal contamination, pH, dissolved
      organic carbon (DOC) and alkalinity. Lakes situated closest to emission point
      source had lower pH, alkalinity and DOC and higher aqueous metal concentrations
      than other lakes in this study. Fish from these lakes displayed higher liver
      metal concentrations. Seasonal variations in liver metal concentrations were
      observed in the most metal-contaminated lakes, with higher Cu levels in the
      spring and higher Zn and Ni concentrations in the fall. These fish had lower
      indicators of physical condition than fish from cleaner lakes. In particular,
      more metal-contaminated fish were smaller for a similar age, indicating slower
      growth rate, and had lower relative condition factor and scaling coefficients.
      The scaling coefficient is a descriptor of the growth pattern of fish, and higher
      values indicate increased weight gain per unit of growth in length. Negative
      (P<0.05) relationships are reported between lake alkalinity and liver Cu
      concentration (in both seasons) and Zn concentration (in spring only). In both
      seasons mean liver Cu content was negatively associated (P<0.05) with the scaling
      coefficient of the fish samples. With these data, we propose the use of the
      scaling coefficient as a simple biomonitoring tool to detect metal effects on the
      physical condition of yellow perch. Data presented here provide information on
      seasonal variations in liver metal concentration and condition of yellow perch
      that should be considered in the design of field studies investigating
      physiological effects of metals in wild fish. This work also describes a gradient
      of lake and fish metal contamination that is related to the physical condition of
      yellow perch. This system provides a unique research opportunity to further our
      limited knowledge of the effects of metals on the physiology of wild fish.

PMID- 12062155
TI  - cDNA cloning and characterization of an aryl hydrocarbon receptor from the harbor
      seal (Phoca vitulina): a biomarker of dioxin susceptibility?
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated
      aromatic hydrocarbons (PHAHs) are found at high concentrations in some marine
      mammals. Species differences in sensitivity to TCDD and PHAHs are a major
      limitation in assessing the ecological risk to these animals. Harbor seals
      accumulate high levels of PHAHs and are thought to be highly sensitive to the
      toxic effects of these compounds. To investigate the mechanistic basis for PHAH
      toxicity in harbor seals (Phoca vitulina), we sought to characterize the aryl
      hydrocarbon receptor (AHR), an intracellular protein that is responsible for PHAH
      effects. Here we report the cDNA cloning and characterization of a harbor seal
      AHR. The harbor seal AHR cDNA has an open reading frame of 2529 nucleotides that
      encodes a protein of 843 amino acids with a predicted molecular mass of 94.6 kDa.
      The harbor seal AHR protein possesses basic helix-loop-helix (bHLH) and Per-ARNT
      Sim (PAS) domains. It is most closely related to the beluga AHR (82%) and human
      AHR (79%) in overall amino acid identity, indicating a high degree of
      conservation of AHR structure between terrestrial and some marine mammals. The
      ligand binding properties of the harbor seal AHR were determined using protein
      synthesized by in vitro transcription and translation from the cloned cDNA.
      Velocity sedimentation analysis on sucrose gradients showed that the harbor seal
      AHR exhibits specific binding of [(3)H]TCDD. The [(3)H]TCDD-binding affinity of
      the harbor seal AHR was compared with that of the AHR from a dioxin-sensitive
      mouse strain (C57BL/6) using a hydroxylapatite assay. The equilibrium
      dissociation constants of seal and mouse AHRs were 0.93+/-0.19 and 1.70+/-0.26
      nM, respectively. Thus, the harbor seal AHR bound TCDD with an affinity that was
      at least as high as that of the mouse AHR, suggesting that this seal species may
      be sensitive to PHAH effects. The characteristics of the AHR potentially can be
      used as a biomarker of susceptibility to dioxin-like compounds, contributing to
      the assessment of the risk of these compounds to marine mammals and other
      protected animals.

PMID- 12062156
TI  - Antioxidant enzymes and peroxisome proliferation in relation to contaminant body
      burdens of PAHs and PCBs in bivalve molluscs, crabs and fish from the Urdaibai
      and Plentzia estuaries (Bay of Biscay).
AB  - With the aim of studying levels of antioxidant and peroxisomal enzymes and the
      structure of peroxisomes in relation to body burdens of polycyclic aromatic
      hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), mussels Mytilus
      galloprovincialis, oysters Crassostrea sp., crabs Carcinus maenas and mullets
      Mugil cephalus were sampled in two Basque estuaries (Bay of Biscay): Urdaibai
      (Laida, Txatxarramendi, Arteaga, and downstream a sewage treatment plant-STP) and
      Plentzia. In general, animals showed higher concentrations of contaminants in
      winter than in summer and no relevant differences were detected among locations.
      Conversely, antioxidant enzyme activities were higher in summer. Enzyme
      expression was studied in mullets using immunochemical methods. By immunoblotting
      season-dependent differences were detected for Mn-superoxide dismutase (Mn-SOD).
      As for the immunohistochemical staining, mullets sampled in summer in Plentzia
      showed significantly higher optical densities for acyl-CoA oxidase and lower for
      both Cu,Zn-SOD and Mn-SOD than those collected downstream a STP as well as higher
      catalase immunostaining than those collected in winter. Peroxisomal volume
      density (V(vp)) of mussels sampled in Laida and Txatxarramendi did not show
      seasonal variations, while for oysters collected in Laida and Arteaga V(vp) was
      higher in summer. Crab and mullet V(vp) were also higher in summer. In
      conclusion, the estuaries of Urdaibai and Plentzia can be considered as low to
      moderately polluted areas and levels of PAHs and PCBs do not show marked
      variations apart from seasonal variations. Animals can be adapted to low
      pollution conditions and, under these circumstances, seasonal factors might
      affect biomarker responses to a greater extent than pollution variations.

PMID- 12062157
TI  - Vitellogenin mRNA regulation and plasma clearance in male sheepshead minnows,
      (Cyprinodon variegatus) after cessation of exposure to 17 beta-estradiol and p
      nonylphenol.
AB  - Research was conducted to determine the kinetics of hepatic vitellogenin (VTG)
      mRNA regulation and plasma VTG accumulation and clearance in male sheepshead
      minnows (Cyprinodon variegatus) during and after cessation of exposure to either
      17 beta-estradiol (E2) or para-nonylphenol (NP). Adult fish were continuously
      exposed to aqueous measured concentrations of 0.089 and 0.71 microg E2 per l, and
      5.6 and 59.6 microg NP per l for 16 days using an intermittent flow-through
      dosing apparatus. Fish were sampled on days 8 and 16 of exposure followed by
      sampling at discrete intervals for up to 96 days post-exposure. At each interval
      five fish were randomly sampled from each concentration and hepatic VTG mRNA and
      serum VTG levels for individual fish determined by slot blot and direct enzyme
      linked immunosorbent assay (ELISA), respectively. Exposure to E2 and NP resulted
      in a dose dependent increase in hepatic VTG mRNA and plasma VTG over the course
      of the 16-day exposure period. Mean plasma VTG levels at day 16 were >100 mg/ml
      for both high doses of E2 and NP, and >20 mg/ml for the low exposure treatments.
      Within 8 days post-exposure, hepatic VTG mRNA levels returned to baseline in both
      high and low E2 treatments but remained elevated 2-4 fold in the NP treatments.
      Due to a shortened sampling period, a clearance rate for plasma VTG in the 5.6
      microg NP per l treatment could not determined. In the 0.089, 0.71 microg E2 per
      l, and 59.6 microg NP per l treatments, VTG levels began decreasing within 4 days
      after exposure cessation and exhibited an exponential rate of elimination from
      plasma. Clearance rates for 0.71 microg E2 per l and 59.6 microg NP per l were
      not significantly different (P=0.47), however, both demonstrated significantly
      higher rates of clearance (P<0.02) than observed in the 0.089 microg E2 per l
      treatment. Our results indicate that hepatic VTG mRNA rapidly diminishes after
      cessation of estrogenic exposure in sheepshead minnows, but plasma VTG clearance
      is concentration and time dependent and may be detected at measurable levels for
      months after initial exposure to an estrogenic compound.

PMID- 12062158
TI  - Effects of 4-nonylphenol on gene expression of pituitary hormones in juvenile
      Atlantic salmon (Salmo salar).
AB  - Alkylphenols such as 4-nonylphenol (NP) are one of the wide variety of
      environmental chemicals reported to have estrogenic effects in both in vitro and
      in vivo studies. Induction of eggshell zona radiata proteins (Zrp) and
      vitellogenin (Vtg) mRNA and protein synthesis in the liver are widely used
      biomarkers for xenoestrogen exposure in fish. However, little work has been done
      to characterize the molecular effects of xenoestrogens on other potential target
      organs such as the pituitary. To evaluate pituitary effects and develop new
      potential biomarkers for xenoestrogens, the influences of NP and 17beta-estradiol
      (E2) on the mRNA levels of pituitary gonadotropic hormone (GTH) beta subunits
      [leutinizing hormone beta (LH beta or GTH II beta) and follicle stimulating
      hormone beta (FSH beta or GTH I beta)], prolactin (PRL), growth hormone (GH) and
      the pituitary specific transcription factor (Pit-1) were investigated in
      individual male and female juvenile Atlantic salmon (Salmo salar), 3 days after a
      single intraperitoneal (i.p.) injection. In one experiment, fish were injected
      with NP (125 mg/kg body weight (BW)) or E2 (5 mg/kg BW) and a semi-quantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) method was used to
      analyze LH beta and FSH beta mRNA levels. In the second experiment, fish were
      injected with three doses of NP (10, 50, 125 mg/kg BW) or a single dose of E2 (5
      mg/kg BW) and Northern blot analysis was used to quantify LH beta, FSH beta, PRL,
      GH and Pit-1 mRNAs. Both NP (50 and 125 mg/kg BW) and E2 significantly induced LH
      beta mRNA levels (P<0.01), but only in females. The highest dose of NP (125 mg/kg
      BW) significantly induced Pit-1 mRNA in males (P<0.01). NP did not have
      significant effects on any of the other pituitary transcripts. NP induced LH beta
      mRNA synthesis in females by up to 6-fold and the changes appeared to correlate
      with the increases in hepatic Vtg and Zrp mRNA levels. The results show that LH
      beta mRNA assay in female juvenile salmonids may be used as a marker for
      pituitary effects of xenoestrogens. The data also suggest that NP may have the
      potential to perturb the regulation of LH beta gene expression by mimicking E2.

PMID- 12062159
TI  - The awesome power of multiple model systems: interpreting the complex nature of
      spindle checkpoint signaling.
AB  - The spindle checkpoint coordinates the cell biology of mitosis with cell-cycle
      progression. It ensures that sister-chromatid separation only takes place when
      all kinetochores have formed stable bipolar microtubule attachments. Here, we
      discuss recent advances in our understanding of what activates this checkpoint
      pathway, the molecular nature of the checkpoint signal and its mode of
      transmission, and how the checkpoint might be inactivated.

PMID- 12062160
TI  - RECKing MMP function: implications for cancer development.
AB  - Cancer is a multistage process requiring progressive genetic and epigenetic
      changes in neoplastic and responding stromal cells. Many alterations that occur
      during the process of malignant progression are regulated by the matrix
      metalloproteinase (MMP) family of extracellular proteases and their endogenous
      inhibitors. Recent work has identified a new cell-surface inhibitor of MMPs -
      RECK. RECK regulates MMP-induced pericellular signaling cascades during
      embryogenesis and tumorigenesis. Homozygous loss of RECK results in embryonic
      lethality and attenuated tumor development in adults - thus providing further
      support for an efficacious role for protease inhibitors as anticancer
      therapeutics.

PMID- 12062161
TI  - Understanding actin turnover - no longer a mere speckle on the horizon.

PMID- 12062162
TI  - VCP - the missing link in protein degradation?

PMID- 12062163
TI  - Drosophila veto puts a stop to cell survival.

PMID- 12062164
TI  - FAP52 - a new partner for filamin in actin cytoskeleton organization.

PMID- 12062165
TI  - What price prolonging worm's estate?

PMID- 12062168
TI  - From UBA to UBX: new words in the ubiquitin vocabulary.
AB  - Ubiquitination is a versatile tool of eukaryotic cells for controlling the
      stability, function and subcellular localization of proteins. The variety of
      cellular processes regulated by ubiquitination demands high substrate specificity
      of the ubiquitination machinery as well as the existence of diverse downstream
      effector proteins interacting with ubiquitinated substrates. Most of these
      cellular effectors are characterized by a modular composition of ubiquitin
      binding motifs and further domains mediating specific functions. Here, I give an
      overview of important ubiquitin-related protein motifs, including the UBA, UIM,
      UBD and UBX domains, and propose a model for the role of subclasses of UBA-domain
      containing proteins in ubiquitin-mediated proteolysis.

PMID- 12062166
TI  - Attention, neurons, this CDK could save your life!

PMID- 12062169
TI  - Centrosomes and cancer: lessons from a TACC.
AB  - The recent discovery that many cancer cells have centrosomal abnormalities
      suggests a link between centrosomes and cancer. Members of the transforming
      acidic coiled-coil (TACC) family of proteins have been implicated in cancer and
      are concentrated at centrosomes, where they regulate microtubule stability. I
      discuss a model of how the TACC proteins might contribute to cancer. This model
      predicts that defects in TACC function can make important contributions to the
      development of cancer but are unlikely to be the primary cause of cancer. The
      model might also apply to several other centrosomal proteins that have been
      linked to cancer.

PMID- 12062170
TI  - Joining the cell survival squad: an emerging role for protein kinase CK2.
AB  - Protein kinase CK2 (formerly known as casein kinase 2) is a serine/threonine
      protein kinase whose functions have been under investigation for over three
      decades, leading to the recognition that it interacts with several signaling
      pathways. Recent demonstrations of signal-mediated dynamic localization of CK2
      and the identification of new signaling targets for it have converged to indicate
      an unexpected function for this protein kinase: cell survival. Here, we summarize
      our emerging knowledge about how CK2 might participate in the transduction of
      survival signals.

PMID- 12062171
TI  - Yeast autophagosomes: de novo formation of a membrane structure.
AB  - Autophagy - the degradation of organelles and cytoplasmic material - occurs
      through dynamic rearrangements of cellular membrane structures. Following the
      induction of autophagy, newly formed autophagosomes transfer cytosolic materials
      to the lysosome or vacuole for degradation. The autophagosome is an organelle
      destined for degradation, suggesting that the membrane structure is formed de
      novo many times. The autophagosome is formed through the nucleation, assembly and
      elongation of membrane structures. The concerted action of several Apg/Aut/Cvt
      proteins around a characteristic subcellular structure (the preautophagosomal
      structure) is the key to understanding this novel type of membrane-formation
      process.

PMID- 12062172
TI  - Sphingosine 1-phosphate signaling: providing cells with a sense of direction.
AB  - Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite that regulates diverse
      biological functions. S1P has been identified as a high-affinity ligand for a
      family of five G-protein-coupled receptors, known as the S1P receptors. The
      physiological role of the S1P receptor S1P(1) in vascular maturation was recently
      revealed by gene disruption in mice. In addition to other cellular processes, the
      binding of S1P to its receptors regulates motility and directional migration of a
      variety of cell types, including endothelial cells and vascular smooth muscle
      cells. This review focuses on the important role of S1P and its receptors in cell
      migration and describes a new paradigm for receptor cross-communication in which
      transactivation of S1P(1) by a receptor tyrosine kinase (PDGFR) is crucial for
      cell motility.

PMID- 12062173
TI  - Hugh E. Huxley: birth of the filament sliding model of muscle contraction.
AB  - Hugh E. Huxley used a combination of X-ray diffraction and electron microscopy to
      define the structural basis for muscle contraction. He developed the entirely new
      concept of movement based on the relative motion of two elongated protein
      polymers powered by the action of independent molecular motors. The concept
      applies to a large number of cell motility mechanisms.

PMID- 12062174
TI  - Pictures in cell biology. GSK-3 and regulation of kinesin function.

PMID- 12062175
TI  - The regional difference of viscoelastic property of bovine temporomandibular
      joint disc in compressive stress-relaxation.
AB  - An in vitro experimental technique was performed to measure the viscoelastic
      properties of the bovine disc. Thirteen TMJ discs from young cattle (3-year-old)
      were used. Each disc was divided into five specimens of anterior, central,
      posterior, lateral and medial regions, and they were used for compression tests.
      A series of stress-relaxation tests was conducted for each specimen from 5%
      strain up to 20% strain with 5% intervals. The stress-relaxation was monitored
      over a period of 5 min. Each region exhibited a different biomechanical behavior,
      which is presumably related to the organization and distribution of proteoglycans
      that indirectly modulate the stiffness of the collagen network. It is suggested
      that an improved understanding of the viscoelastic properties of the disc under
      function may guide consideration for design and selection of biomaterials for TMJ
      reconstruction.

PMID- 12062176
TI  - Development and evaluation of a novel decellularized vascular xenograft.
AB  - Although autogenous saphenous vein remains the standard for coronary and
      infrapopliteal bypass, many patients do not have a suitable vein. Attempts at
      developing a small-caliber vascular graft have failed largely due to occlusion,
      neointimal hyperplasia, or aneurismal degradation. We have designed and
      characterized a novel small-caliber vascular xenograft that may overcome these
      failure modes. To reduce immune reactions, porcine common carotid arteries were
      decellularized by enzymatic and detergent treatments. Histology and electron
      microscopic examination showed complete removal of cellular components while the
      extracellular matrix structure remained intact. To reduce thrombogeneity,
      decellularized vascular grafts were covalently linked with heparin. The
      efficiency of heparin linkage was demonstrated with toluidine blue staining and
      the antithrombogeneity of the heparin-treated grafts was demonstrated with a clot
      time test. Mechanical testing of the graft was performed. Decellularized-heparin
      treated grafts were similar in compliance to fresh vessels and burst testing
      showed grafts to withstand pressures exceeding 10 times physiologic blood
      pressure. There was no difference in suture retention strength between fresh
      vessels and decellularized-heparin-treated grafts. Decellularized, heparinized
      grafts were implanted in dogs as carotid artery bypass grafts and showed smooth
      muscle cells densely populating the wall, and endothelial cells lining the lumen
      by two months. This study provides a new strategy to develop a small-caliber
      vascular graft with excellent mechanical properties, antithrombogeneity, and
      tissue compatibility.

PMID- 12062177
TI  - An effective coding technique for the compression of one-dimensional signals
      using wavelet transforms.
AB  - This paper introduces an effective technique for the compression of one
      dimensional signals using wavelet transforms. It is based on generating a binary
      stream of 1s and 0s that encodes the wavelet coefficients structure (i.e.,
      encodes the locations of zero and nonzero coefficients). A new coding algorithm,
      similar to the run length encoding, has been developed for the compression of the
      binary stream. The compression performances of the technique are measured using
      compression ratio (CR) and percent root-mean square difference (PRD) measures. To
      assess the technique properly we have evaluated the effect of signal length,
      threshold levels selection and wavelet filters on the quality of the
      reconstructed signal. The effect of finite word length representation on the
      compression ratio and PRD is also discussed. The technique is tested for the
      compression of normal and abnormal electrocardiogram (ECG) signals. The
      performance parameters of the proposed coding algorithm are measured and
      compression ratios of 19:1 and 45:1 with PRDs of 1% and 2.8% are achieved,
      respectively. At the receiver end, the received signal is decoded and inverse
      transformed before being processed. Finally, the merits and demerits of the
      technique are discussed.

PMID- 12062178
TI  - A wavelet packets decomposition algorithm for quantification of in vivo (1)H-MRS
      parameters.
AB  - In this paper a novel method for the extraction of magnetic resonance
      spectroscopy (MRS) parameters is presented. The method applies the traditional
      time-domain linear prediction singular value decomposition (LPSVD) on the set of
      orthonormal sub-signals obtained by wavelet packets (WP) decomposition of the
      original free induction decay (FID) signal. Using the properties of WP the
      desired, optimal, sub-band FID decomposition is obtained and used to
      progressively separate the different metabolic components in distinct sub-bands.
      A pseudo-optimal WP tree is obtained using the minimum description length (MDL)
      criteria. The proposed algorithm preserves all the advantages of the traditional
      LPSVD method, but the WP decomposition considerably improves the LPSVD
      performances in the presence of noise. The paper addresses this aspect in details
      by comparing the innovative sub-band and the traditional full-band approaches.
      Algorithms are tested on simulated signals that mimic real MRS data.

PMID- 12062179
TI  - A new orthotic device in the non-operative treatment of idiopathic scoliosis.
AB  - A transverse force system, consisting of an anterior progression force
      counteracted by a posterior force and torque, acts on the vertebrae of a
      scoliotic spine. The aim of the newly introduced TriaC brace is to reverse this
      transverse force pattern by externally applied and constantly present orthotic
      forces. In the frontal plane the force system in the TriaC brace is in accordance
      with the force system of the conventional braces. However, in the sagittal plane
      the force system acts only in the thoracic region. As a result, there is no
      pelvic tilt, and it provides flexibility without affecting the correction forces
      during body motion. In the current preliminary study it is demonstrated that the
      brace prevents further progression of the Cobb angle and axial rotation in
      idiopathic scoliosis. The new brace has the added advantage of comfort for the
      wearer, and it offers a better cosmetic appearance, as well as, potentially, a
      better compliance.

PMID- 12062180
TI  - Three-dimensional analysis and visualization of regional MR signal intensity
      distribution of articular cartilage.
AB  - The aim of this study was to develop a technique for analyzing and visualizing
      the regional, three-dimensional signal intensity distribution of articular
      cartilage in MR images, as a potential surrogate marker of structural or
      biochemical alterations in early osteoarthritis. Exemplary MR-images of human
      patellae were acquired at a resolution of 1.5 x 0.31 x 0.31 mm(3), using a
      gradient-echo sequence with water excitation, and by combining three data sets to
      secondary images of proton density. After segmentation of the cartilage outlines,
      these were transferred to the other images. Contiguous slices were automatically
      divided into sub-regions that extend from the surface to the bone interface
      (layers) as well as from medial to lateral (sections). The signal intensity was
      then calculated and projected onto a three-dimensional representation of the
      articular surface, either by averaging through the depth (sections) or by
      visualizing the signal intensity at distinct levels in depth (layers). The
      exemplary data indicate that the reproducibility for regional analyses is in the
      same range as for the entire patellar cartilage, and that the distribution
      patterns of proton density delineated with MRI are in agreement with the
      literature. In conjunction with suitable MR protocols, this post-processing
      technique has potential to allow for detection and quantification of early
      degenerative processes in cartilage, before macro-morphological lesions occur.

PMID- 12062181
TI  - Accuracy estimations of testing of infusion devices using weighing balances.
AB  - The role of gravimetric balances in the evaluation of infusion devices is
      considered from a perspective of accuracy for such evaluations and the actual
      physical and interface characteristics of such balances as specialist measurement
      devices. In particular, the dynamic properties of weighing balances are discussed
      in relation to observations of variation of response times and stability
      settings. This work has identified characteristics, which may influence flow
      measurement techniques as defined by measurement protocols adopted by relevant
      standards and those developed independently. While a dominant error is introduced
      due to balance resolution error, consideration of timing errors associated with
      data capture is also essential.

PMID- 12062182
TI  - A versatile drop foot stimulator for research applications.
AB  - Drop Foot Stimulators are used to correct hemiplegic drop foot by synchronising
      the application of Functional Electrical Stimulation (FES) of the Common Peroneal
      Nerve (CPN) to the swing phase of the gait cycle. A research Drop Foot Stimulator
      (DFS) has been developed with a very flexible architecture to enable the
      investigation of a variety of gait-correction strategies. The portable unit has
      been carefully designed to optimise functionality while keeping its size and
      power consumption to a minimum. The device has two channels of stimulation, with
      all parameters of stimulation for each channel independently programmable. Four
      analogue and four digital sensor input channels are provided with a wide variety
      of sensor types possible. A microcontroller core is utilised to enable the
      implementation of different control algorithms. A PC-based user interface enables
      easy programming of the system configuration.

PMID- 12062183
TI  - Influence of head constraint and muscle forces on the strain distribution within
      the intact femur.

PMID- 12062184
TI  - Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF
      related macrophage activation.
AB  - Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate
      in serum of cancer patients and be responsible for deglycosylation of Gc protein,
      which is a precursor of GcMAF-mediated macrophage activation cascade, finally
      leading to immunosuppression in advanced cancer patients. We studied the
      biochemical characterization of alpha-NaGalase from several human tumor cell
      lines. We also examined its effect on the potency of GcMAF to activate mouse
      peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage
      activation cascade. The specific activity of alpha-NaGalases from human colon
      tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver
      cells (Chang liver cell line) were evaluated using two types of substrates;
      GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type
      substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha
      NaGalase, had higher substrate specificity to the exo-type substrate than to the
      endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance
      superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor
      cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is
      different in biochemical characterization compared to normal alpha-NaGalase from
      normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase
      decreases the potency of GcMAF on macrophage activation.

PMID- 12062185
TI  - Effect of the source and detector configuration on the detectability of breast
      cancer.
AB  - Breast cancer causes the death of more than 150,000 women in the United States
      each year. Pregnant women cannot undergo mammography due to its dangerous side
      effects and, for younger women, a mammogram does not differentiate tumor from
      their dense breast tissue. Breast tumors usually become a localized absorber in
      the near infrared (NIR) wavelength region, because of the increased hemoglobin
      concentration around the area of the tumor. Therefore, NIR has a high potential
      to detect breast cancer without side effects. A computer simulation solving the
      photon transfer equation was used to study the detectability of various tumor
      sizes embedded in the breast model at various depths, for both reflectance and
      transmittance. Previous reflectance studies demonstrated that increasing the S-D
      separation does not necessarily allow the photons to penetrate deeper in the
      medium. The optimum S-D separation for breast tissue was found to be 3.0 cm,
      where the light penetrates up to 1.7 cm. Studies on the photon path in
      transmittance demonstrate that, at high modulation frequencies, (e.g. 1.0 GHz),
      the photon path becomes more coherent. Therefore, for transmittance measurements,
      high modulation frequencies can be useful to localize deep tumors. Multi
      frequency, multi- S-D separation reflectance can be used to provide information
      on tumor depth.

PMID- 12062187
TI  - Non-standard O(2) consumption-temperature curves during rest and isometric
      exercise in human skeletal muscle.
AB  - The present work was aimed at measuring intramuscular oxygen consumption (O(2))
      as a function of temperature (T), in human forearm, during rest and aerobic
      isometric exercise (4% of the maximal voluntary contraction, MVC). Based upon
      results from in vitro experiments performed on isolated mitochondria of animal
      species, it was hypothesised that, during isometric exercise, the O(2)-T curve
      should display a maximum for some 'optimal' T. Intramuscular T and measurements
      were performed using a combined deep body temperature/near infrared probe during
      muscle cooling. At rest, O(2) increased non-linearly and monotonically as a
      function of T (n=8). O(2) increased approximately 2 times when going from 26 to
      36 degrees C. A log(O(2))-T plot or a log(O(2))-1/T did not linearise the data.
      During isometric contraction, O(2) values at 26.8+/-0.6, 28.6+/-0.9, 31.9+/-0.9
      and 35.9+/-0.9 degrees C were 3.04+/-1.26, 7.60+/-1.64, 4.43+/-1.95, and 6.64+/
      1.37 micromol 100 g(-1) min(-1), respectively (n=6). The O(2) value at 28.6
      degrees C was significantly higher (P<0.05) than that at 26.8 and 31.9 degrees C.
      The 'sudden' O(2) change at 28.6 degrees C is compatible with the phenomenon
      observed at the mitochondrial level.

PMID- 12062186
TI  - Comparison and modulation of angiogenic responses by FGFs, VEGF and SCF in murine
      and human fibrosarcomas.
AB  - The effects of angiogenic growth factors on the growth, vascular architecture and
      the downstream cytokine signaling of sarcomas are unknown. These are of potential
      great importance since sarcoma, like endothelium, is of mesodermal origin and
      therefore could grow in response to these factors. Three human sarcomas
      (leiomyosarcoma SK-LMS-1, liposarcoma SW872 and fibrosarcoma SW684) and one
      murine fibrosarcoma (KHT) were grown in nude and C3H/He mice, respectively. Tumor
      structural vessels, perfused vessels and hypoxia were quantified
      immunohistochemically. Fast-growing murine KHT tumors had a markedly higher
      number of structural vessels compared with the human sarcomas. In both murine and
      human sarcomas, approximately half of the total structural vessels were perfused,
      and the numbers of perfused vessels decreased with increasing tumor volume. In
      vitro, basal mRNA expression of several angiogenic growth factors and their
      receptors differed between two of the human sarcoma cell lines, SK-LMS-1 and
      SW872. Compared with SK-LMS-1, untreated SW872 cells had higher levels of mRNA
      expression for FGF11, FGF14, angiopoietin, CD105 and VEGFR1. Two sarcoma cell
      lines were also treated with 10 ng/ml of six angiogenic growth factors (FGF1,
      FGF2, FGF7, FGF10, VEGF and SCF) for 24 h, and mRNA expression of endogenous FGF
      family members (FGF1, FGF2, FGF10, FGF11, FGF13 and FGF14) were quantitatively
      measured using RNase protection at various times following treatments. Again,
      SW872 cells were more responsive to exogenous growth factor treatment compared
      with SK-LMS-1 cells in terms of the elevation of endogenous FGF mRNA expression.
      In the SW872 cells, all of the exogenous angiogenic growth factor treatments,
      except for VEGF, upregulated endogenous FGF1, FGF2 and FGF14 mRNA expression. The
      SK-LMS-1 cells, in contrast, only responded to exogenous FGF1, FGF7 and FGF10,
      but did not respond to VEGF.

PMID- 12062188
TI  - Design, synthesis and biological activities of antiangiogenic hypoxic cytotoxin,
      triazine-N-oxide derivatives.
AB  - For cancer therapy, hypoxia represents an important tumor specific target.
      Therefore we designed and synthesized antiangiogenic hypoxic cytotoxins as
      'hypoxia modifiers'. They can be activated bioreductively in hypoxic cells to
      kill the oxygen-deficient tumor cells selectively and prevent their re-growth.
      The aromatic heterocycle di-N-oxides, tirapazamine (TPZ), TX-1102, and TX-402
      inhibited growth of EMT6/KU cells, SAS/neo cells, and SAS/Trp248 cells (mutant
      p53 gene transformant) under hypoxic condition. They also induced apoptosis
      selectively at a dose of 10 microM each under hypoxic condition for 5 h. Their
      hypoxic cytotoxicities and apoptosis inducing activities were p53-independent
      because the activities in SAS/neo cells were almost similar to that in SAS/Trp248
      cells. In angiogenesis inhibition assay using chick embryo chorioallantoic
      membrane (CAM), TPZ, TX-1102, TX-402 and TX-1033 showed 40, 25, 60 and 60%
      inhibition of angiogenesis each at a dose of 10 microg/CAM. On the other hand,
      the nitrosopyrimidine, TX-1041 had neither antiangiogenic activity nor
      cytotoxicity. Therefore the di-N-oxide group is thought to be required for the
      biological activities. TX-1102 was a potent antiangiogenic hypoxic cytotoxin
      inducing apoptosis p53-independently.

PMID- 12062189
TI  - Design and synthesis of 2,6-diprenyl-4-iodophenol TX-1952 with a novel and potent
      anti-peroxidative activity.
AB  - The structure-based elucidation of 2,4,6-tri-substituted phenols for their
      antioxidative and anti-peroxidative effects has been investigated using TX-1952
      (2,6-diprenyl-4-iodophenol), TX-1961, TX-1980, BTBP and BHT. In the inhibition of
      mitochondrial lipid peroxidation, the inhibitory activity of 2,6-di-tert-butyl-4
      bromophenol (BTBP) (IC(50)=0.17 microM) was twice as high as that of 2,6-di-tert
      butyl-4-methylphenol (BHT) (IC(50)=0.31 microM). This result shows that the 4
      halogen group increases inhibitory activity for mitochondrial lipid peroxidation.
      Besides, TX-1952 (IC(50)=0.60 microM) was the highest inhibitor among 2,6
      diprenyl-4-halophenols, followed by TX-1961 (IC(50)=0.93 microM) and TX-1980
      (IC(50)=1.2 microM). In 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging
      experiments, the activity of TX-1952 (IC(0.200)=53.1 microM) was lower than that
      of BHT (IC(0.200)=33.7 microM) and BTBP (IC(0.200)=16.0 microM), but TX-1952 and
      BHT showed the same HOMO energy (-8.991 eV). These results suggest that the two
      prenyl groups at ortho position hinder the phenolic hydrogen abstraction by DPPH
      radical. These findings demonstrated that TX-1952 was a novel and potent
      inhibitor for lipid peroxidation.

PMID- 12062190
TI  - Outer retinal anoxia during dark adaptation is not a general property of
      mammalian retinas.
AB  - The purpose of this study was to measure the intraretinal oxygen distribution
      across the retina under conditions, which maximise outer retinal oxygen
      consumption. In particular, we looked for evidence of increased oxygen delivery
      from the choroid and the deep retinal capillary layer, and whether or not this
      was sufficient to avoid the development of intraretinal anoxia. Under dark
      adapted conditions the photoreceptors need additional energy, at least part of
      which is derived from increased oxidative metabolism. In earlier studies in the
      cat retina it was revealed that dark adaptation could render some regions of the
      outer retina anoxic. The present study of the in vivo oxygen distribution across
      the rat retina in light and dark found no evidence of outer retinal anoxia in the
      dark. This was despite a mean increase of 52.6+/-11.4% (n=7) in outer retinal
      oxygen consumption in the dark. The mean value for the minimum outer retinal
      PO(2) in the dark was 5.2+1.2 mmHg. Oxygen delivery from both the choroid and the
      deep retinal capillary layer increased in the dark (P<0.01, and P<0.001,
      respectively). It is argued that the ability of the deep capillary layer to
      compensate for changes in oxygen demand in the outer retina is an important
      element in the maintenance of homeostasis in the retina. This is in addition to
      the role of the deep capillary layer in supplying oxygen to the highly consuming
      plexiform layers within the inner retina. These findings in the rat retina also
      demonstrate that intraretinal anoxia in the dark, is not, as implied by earlier
      work in the cat, a general feature of mammalian retinas.

PMID- 12062191
TI  - Oxygen transport to skeletal muscle working at VO(2)max in acute hypoxia:
      theoretical predictions.
AB  - The influence of acute hypoxia (30 < or = PaO(2) < or = 100 mmHg) on the values
      of VO(2)max and parameters of oxygen transport in muscle working at VO(2)max was
      studied. We investigated muscle working under different values of blood flow F
      (60 < or = F < or = 120 ml/min per 100 g), blood pH (7.0-7.6), and different
      diffusion conditions. Investigations were performed on a computer model of O(2)
      delivery to and O(2) consumption in the working muscle. VO(2)max, PvO(2), pO(2)-
      and VO(2)-distribution in muscle fiber were calculated. It was shown that the
      greater the degree of arterial hypoxemia, the lower the muscle VO(2)max and blood
      pO(2) values. When working at VO(2)max, the average and minimal values of tissue
      pO(2) depend on PaO(2). The greater the blood flow through muscle, the greater
      the VO(2)max. However, with an increasing degree of arterial hypoxemia, the
      effect of F and blood pH on the value of VO(2)max is weakened. The diffusion
      conditions produced a powerful influence on the VO(2)max value. At reduced PaO(2)
      they are the most important limiting factors of O(2) supply to muscle working at
      maximal effort.

PMID- 12062192
TI  - A multi-layer model of retinal oxygen supply and consumption helps explain the
      muted rise in inner retinal PO(2) during systemic hyperoxia.
AB  - A multi-layer mathematical model of oxygen supply and consumption in the rat
      retina is described. The model takes advantage of the highly layered structure of
      the retina and the compartmentalisation of the available oxygen sources. The
      retina is divided into eight layers, each with a distinct oxygen consumption or
      supply rate. When applied to the available data from intraretinal oxygen
      measurements in the rat under normal physiological conditions, a close fit
      between the model and the data was achieved (r(2)=0.98+0.005, n=6). The model was
      then used to investigate recent evidence of oxygen regulating mechanisms in the
      rat retina during systemic hyperoxia. Fitting our model to the experimental data
      (r(2)=0.988+0.004, n=25) allowed the relative oxygen delivery or consumption of
      the key retinal layers to be determined. Two factors combine to produce the
      relative stability of inner retinal oxygen levels in hyperoxia. The retinal layer
      containing the outer plexiform layer/deep retinal capillaries, switches from a
      net source to a net consumer of oxygen, and the oxygen consumption of the outer
      region of the inner plexiform layer increases significantly. The model provides a
      useful tool for examining oxygen consumption and supply in all retinal layers,
      including for the first time, those layers within the normally perfused inner
      retina.

PMID- 12062193
TI  - Differences in oxygen re-saturation of thigh and calf muscles after two treadmill
      stress tests.
AB  - Spatially resolved near-infrared oximeters quantify non-invasively muscle
      haemoglobin oxygen saturation (TOI) and, indirectly, local venous oxygen
      saturation (SvO(2)) and blood flow (MBF). TOI, SvO(2) and MBF of vastus lateralis
      and medial gastrocnemius were investigated after 5-min walking (3.2 km/h) and
      running (9.6 km/h) (n=7). The values of TOI were unchanged in the vastus
      lateralis during walking, whilst decreased during running in both muscles. For
      both muscles, TOI and SvO(2) values after walking were significantly greater than
      those found after running (P=0.043). The TOI went back (in 2 min) to its baseline
      value after walking in both muscles, whilst more slowly (in 4 min) after running
      in vastus lateralis. After running TOI of medial gastrocnemius had a tendency to
      be higher than the baseline value (reactive hyperaemia), concomitantly to the
      high MBF (twice the control value). The diverse oxygen demand in the stress tests
      and the consequent different pattern of TOI recovery reflect the different
      engagement of the two muscles. In conclusion, these results demonstrated the
      utility of TOI, independent of MBF and SvO(2), to be measured upon specific
      stress testing for differentiating the severity of peripheral vascular diseases
      and for assessing the collateral blood flow.

PMID- 12062194
TI  - Evaluation of PO(2) profiles to describe the oxygen pressure field within the
      tissue.
AB  - Oxygen transport within the tissue occurs by diffusion and produces an oxygen
      pressure field. To describe its heterogeneity histograms of local PO(2) values
      are used. PO(2) profiles measured with small polarographic microelectrodes
      demonstrate that a large heterogeneity of the amplitudes of local PO(2) changes
      (Delta PO(2)/distance) exists. Therefore, we investigated whether the amplitudes
      of local PO(2) changes can be used to obtain additional information about the
      state of oxygen supply. Six PO(2) profiles in the renal cortex of the dog were
      evaluated. The frequency histograms of the local PO(2) values showed a normal
      oxygen supply of the kidneys. To analyze the heterogeneity of the amplitudes of
      the local PO(2) changes every 10 microm the (Delta PO(2)/distance) values were
      determined. Most of the amplitudes steps are in the range of +/-10 torr. The
      frequency histogram of the amplitudes steps shows a symmetric form: 100% are
      between -35 and +49 torr, 90% between -12 and +11 torr. Changes of the amplitude
      histogram occur if the distances between the selected adjacent points are varied.
      At distances larger than 100 microm the amplitude histograms became
      disintegrated. Interestingly, the local PO(2) histograms remained practically
      unchanged. Therefore we conclude, that by this measuring and evaluation technique
      histograms of the (Delta PO(2)/microm) values are obtained by which the state of
      oxygen supply of local structures can be monitored, probably of the
      microcirculatory unit of capillary oxygen supply. The results demonstrate a well
      regulated oxygen pressure field within the kidney. Similar results were obtained
      from PO(2) profiles measured in the brain cortex (Delta PO(2)/50 microm).

PMID- 12062195
TI  - Cerebral blood flow assessment with indocyanine green bolus transit detection by
      near-infrared spectroscopy in the rat.
AB  - In this study we evaluated the feasibility of measuring cerebral blood flow in
      rats by monitoring the transit of an indocyanine green bolus through the brain
      with multiwavelength near-infrared spectroscopy. Different volumes of a 1 mg/ml
      indocyanine green solution (5, 15, 25, 50 microl) were injected intravenously in
      the search for an optimal dose. Clear transit curves were obtained with all doses
      and a blood flow index could easily be determined. The indocyanine green signal
      obtained with the bolus of 5 microl rapidly returned to baseline and interfered
      minimally with the haemoglobin and cytochrome oxidase signals. This dose was used
      in a second study to evaluate the reproducibility of the signal and the effect of
      hypercapnia. Two groups of rats received 7 repetitive boli of indocyanine green.
      In one group, 7% CO(2) was added to the gas mixture before the second, fourth and
      sixth indocyanine green injection. Hypercapnia consistently caused a significant
      increase in blood flow index, cerebral haemoglobin concentration and O(2)
      saturation. In the control group these variables remained stable in time. We
      conclude that monitoring of the transit of an indocyanine green bolus with
      multiwavelength near-infrared spectroscopy can be used to assess cerebral blood
      flow qualitatively in rats in combination with continuous monitoring of brain
      oxygenation.

PMID- 12062196
TI  - Effects of non-nutritive sucking on heart rate, respiration and oxygenation: a
      model-based signal processing approach.
AB  - Several studies support the idea that the use of pacifiers can reduce the risk of
      Sudden Infant Death Syndrome. To investigate the effect of non-nutritive sucking
      (NNS), we measured heart rate, abdominal respiration, EMG and arterial oxygen
      saturation of 20 neonates. Also, in 10 of these neonates, changes in cerebral
      hemoglobin concentrations were acquired by means of near-infrared spectroscopy.
      Using a parametric technique to model the heart rate as a sum of exponentially
      damped sinusoids, two main frequency components were found in the heart rate
      during NNS: a frequency of approximately 0.08 Hz due to the alternation of
      sucking bursts and pauses, and a frequency of approximately 0.8 Hz that reflects
      the influence of the respiration. Our analysis shows that it is the alternation
      of bursts and pauses itself that causes the increased heart rate variability, and
      that this is not due to increased effort. This suggests that the neuronal
      mechanism regulating NNS also stimulates the heart rate. From our measurements,
      no effect of NNS on cerebral or peripheral oxygenation could be found.
      Furthermore, we show that our model-based signal processing technique is well
      suited for the analysis of non-stationary biomedical signals.

PMID- 12062197
TI  - Inhibitors of mitochondrial complex I attenuate the accumulation of hypoxia
      inducible factor-1 during hypoxia in Hep3B cells.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that
      regulates transcriptional activation of several genes that are responsive to
      oxygen lack, including erythropoietin, vascular endothelial growth factor,
      various glycolytic enzymes and the GLUT-1 glucose transporter. Because
      mitochondria have been postulated to be involved in the regulation of HIF-1, we
      tested the effects of mitochondrial electron transport chain complex I
      inhibitors, rotenone and 1-methyl-4-phenylpiridinium (MPP(+)), on hypoxic-induced
      accumulation of HIF-1 alpha, the regulated component of the dimer. We found,
      consistent with our previous observations in Cath.a and PC12 cells, that rotenone
      and MPP(+) attenuated the HIF-1 alpha hypoxic response. Thus, it can be concluded
      that an intact, functional mitochondrial respiratory chain is required for HIF-1
      alpha accumulation.

PMID- 12062198
TI  - Hypoxia influences generation and propagation of electrical activity in embryonic
      cardiomyocyte clusters.
AB  - The influence of tissue hypoxia on the generation and propagation of excitation
      was studied in spontaneously beating embryonic cardiomyocyte clusters grown in
      eight 9-12 days old embryoid bodies. Within the embryoid bodies one to three
      separately active clusters of cardiomyocytes were found, each having its own
      pacemaker cell. Lowering of tissue PO(2) caused bradycardia as well as arrhythmia
      in all embryoid bodies investigated. The mean frequency of the extracellularly
      recorded action potentials decreased under conditions of pronounced hypoxia from
      a mean of 1.4-1.8 Hz to below 0.8 Hz. In three embryoid bodies hypoxia-sensitive
      as well as hypoxia-tolerant cardiomyocyte clusters were found. The hypoxia
      insensitive cardiomyocytes showed a low frequency of spontaneous activity. In
      addition to the observed changes in the generation of excitation, tissue hypoxia
      caused an approximately 60% reduction in the velocity of conduction within the
      cardiomyocyte clusters. Moreover, in at least one of the eight experiments
      propagation failure with an incomplete block in spread of excitation was
      observed. All hypoxia-induced effects on generation and propagation of embryonic
      cardiomyocyte excitation were completely reversible after reoxygenation.

PMID- 12062199
TI  - Effect of aging on brain energy-metabolism.
AB  - The aging process involves morphological and functional changes in cerebral
      vasculature and deterioration of mitochondrial number and function. Furthermore,
      slow oscillations of cerebral blood flow and oxidative metabolism occur in
      animals under different pathological conditions such as ischemia. The aim of this
      study was to evaluate the effect of aging on energy-metabolism of the rat brain
      during anoxia and normoxia and to further investigate the occurrence of
      oscillations under normoxia in the aging brain. Simultaneous hemodynamical (CBF),
      biochemical (NADH/NAD ratio) and electrical activity from the cerebral cortex
      were measured by means of a multiparametric assembly (MPA) system. Exposure of
      adult rats to anoxia (100% N(2)) resulted in a 36+/-2% elevation of NADH.
      Furthermore, exposure of the aged group to anoxia caused NADH elevation as low as
      9.6+/-4% (P<0.05). The changes in the NADH levels were followed by an increase in
      CBF. In addition, during the normoxic periods, hemodynamic oscillations were
      recorded in the old animals. This study suggests that the structural and
      functional changes that occur in vessels in the aging brain cause disability of
      cerebromicrovessels to optimally deliver nutrients and oxygen to the brain,
      affecting the mitochondrial ability to respond to anoxia. Furthermore, this study
      supports the approach that the hemodynamic oscillations are related to the
      development of a pathological state and are not a normal cerebral function.

PMID- 12062200
TI  - Quantification of cerebral oxygenation by full-spectrum near-infrared
      spectroscopy using a two-point method.
AB  - The aim of this study was to quantify the relative concentrations of
      oxyhemoglobin and deoxyhemoglobin within the light path of the brain and to
      estimate cerebral hemoglobin (Hb) oxygen saturation using full-spectrum near
      infrared spectroscopy (fsNIRS). For this purpose, we developed a novel
      exponential correction equation as well as a two-point spectroscopy method to
      estimate the relative concentrations of Hb and Hb oxygen saturation in biological
      tissues. The results of evaluation of measurements using an in vitro model
      indicated that our fsNIRS method enables accurate and non-invasive measurements
      of Hb content and saturation in a highly scattered medium such as the human
      brain. According to the results of analysis using a hypoxic piglet model, the
      mean cerebral Hb oxygen saturation (SbO(2)) of newborn piglets at an inspired
      oxygen gas concentration of 0.21 was estimated to be 63+/-4% (mean+/-S.D.).
      Umbilical arterial and left internal jugular venous Hb oxygen saturation were
      simultaneously estimated to be 96+/-2% and 52+/-11%, respectively. SbO(2) and
      arterial Hb oxygen saturation values had a linear relationship. The average
      oxygenation state of cerebral tissue is comparable with that of the cerebral
      vein. The results of this study showed that our method can be used to monitor Hb
      oxygen saturation in the neonatal brain at the bedside in an intensive care unit.

PMID- 12062201
TI  - Measurement of cerebral oxygenation in neonates after vaginal delivery and
      cesarean section using full-spectrum near infrared spectroscopy.
AB  - To investigate whether or not the mode of delivery produces differences in
      cerebral oxygenation, cerebral hemoglobin oxygen saturation was measured using
      full-spectrum near infrared spectroscopy in 26 healthy term newborn infants
      immediately after birth. Infants in group 1 (n=20) were delivered vaginally, and
      those in group 2 (n=6) by elective cesarean section. Arterial oxygen saturation
      in the right hand was also measured simultaneously using a pulse oximeter.
      Changes in arterial oxygen saturation showed no significant difference between
      the two groups. The mean+/-S.D. of cerebral hemoglobin oxygen saturation in group
      1 increased rapidly after birth, from 29+/-17% at 2 min to 68+/-6% at 8.5 min,
      followed by an almost constant value (66+/-7% at 15 min). In comparison, cerebral
      hemoglobin oxygen saturation in group 2 also increased rapidly until 8.5 min, but
      after this time decreased significantly to 57+/-5% at 15 min after birth. This
      indicates that the mode of delivery has a marked influence on cerebral
      oxygenation immediately after birth.

PMID- 12062202
TI  - Effect of catecholamines on activity of Na(+), K(+)-ATPase in neonatal piglet
      brain during posthypoxic reoxygenation.
AB  - The present study examined the possible role of dopamine on the response of
      Na(+), K(+)-ATPase activity in the striatum of newborn piglets to 1 h of
      bilateral carotid ligation with hemorrhage and 2 h of recovery. Newborn piglets,
      2-4 days of age and with and without prior treatment with alpha-methyl-p-tyrosine
      (AMT), an inhibitor of catecholamines synthesis, were used for the study. The
      oxygen pressure in the microvasculature of the cortex (PcO(2)) was measured by
      oxygen dependent quenching of the phosphorescence. In sham-operated animals the
      PcO(2) was 50+/-3 torr. Following ligation and hemorrhage the PcO(2) decreased to
      8+/-0.5 torr. After release of ligation and reperfusion PcO(2) increased to 45+/
      4 torr, a value not significantly different from controls, in approximately 30
      min. There were no significant differences in PcO(2) between AMT treated and
      untreated animals. In sham-operated animals striatal Na(+),K(+)-ATPase was 29.1+/
      3 micromol/mg protein per h and decreased by 25% after 2 h of recovery. Depleting
      the brain of catecholamines prior to ligation and hemorrhage abolished this
      decrease. It is postulated that the decrease in the level of dopamine in the
      brain prior to ligation and hemorrhage can be at least partly responsible for the
      observed decrease in activity of Na(+), K(+)-ATPase in the striatum of newborn
      piglets.

PMID- 12062203
TI  - A method for measuring oxygen distributions in tissue using frequency domain
      phosphorometry.
AB  - Phosphorescence lifetime of phosphors dissolved in biological fluids is dependent
      on the local oxygen concentration. When phosphor is added to the blood in vivo
      there is a distribution of lifetimes due to the distribution of oxygen
      concentrations in the blood of the sampled tissue volume. The distribution of
      oxygen can be assessed non-invasively and in practically real-time using
      frequency domain time-resolved phosphorometry. Here we describe a multi-frequency
      system for measurements of oxygen distributions in tissue in vivo.

PMID- 12062204
TI  - Measurement of tumor oxygenation using new frequency domain phosphorometers.
AB  - Oxygen dependent quenching of phosphorescence allows for non-invasive
      measurements of oxygen in tissue. We have designed and constructed a novel multi
      frequency instrument for measurement of phosphorescence lifetimes and developed
      algorithms for determining the distribution of oxygen (oxygen histogram) in the
      microvasculature of tissue with good temporal resolution (Vinogradov et al.,
      2002, Compar. Biochem. A, these proceedings). This technology, in combination
      with a new water soluble near infra red phosphor (Oxyphor G2), was used to
      examine the oxygenation of subcutaneous Q7 tumors grown on the flank of Buffalo
      rats and their response to giving the rats oxygen or carbogen to breathe.
      Phosphorescence was measured using excitation at 635 nm and emission at >700 nm
      (the phosphorescence maximum is near 800 nm). The excitation and collection light
      guides were placed on the surface of the skin of the anesthetized animals
      separated by approximately 0.8 cm. A 6 x 6 or 7 x 7 grid (approx. 4 cm x 4 cm)
      was drawn on the flank and oxygen histograms were measured in each square,
      providing 'images' of the oxygen distribution in the tissue. This procedure
      determines the tissue oxygen distribution at each position in the grid. Regions
      of relative hypoxia (associated with the tumor) can be readily localized and the
      extent of hypoxia quantitatively evaluated.

PMID- 12062205
TI  - Physiological insulin concentrations protect against ischemia-induced loss of
      cardiac function in rats.
AB  - This study determined whether insulin at pre- (fasting) and post-prandial
      concentrations increases coronary blood flow and improves cardiac function after
      acute ischemia during a situation of myocardial stunning. The experiments were
      performed using an isolated, erythrocyte perfused, working rat heart model. To
      the perfusate we added erythrocytes and 1.5% bovine serum albumin to improve
      clinical relevance. The following protocol was used: 8 min baseline performance
      assessment, 10 min pre-ischemic treatment, 12 min global ischemia, 20 min post
      ischemic treatment and 8 min recovery assessment. Vehicle, 10 mIU l(-1) and 100
      mIU l(-1) human insulin were tested (all n=6). No significant vasodilator
      response to insulin was observed either pre- or post-ischemically. After the 12
      min ischemic insult, cardiac function returned dose-dependently to pre-ischemic
      values (function loss with 100 mIU l(-1) insulin: -0.2+/-0.4% vs. vehicle: 10.7+/
      0.8%). This study clearly shows that in our clinically relevant model of moderate
      ischemia (stunning), insulin is highly cardioprotective at physiological
      concentrations. This may be explained primarily by higher glucose uptake,
      improving the myocardial energetic state during ischemia. Therefore, insulin
      should be considered for use when the myocardium is at acute risk for ischemic
      incidents.

PMID- 12062206
TI  - Recovery of radial PO(2) profiles from phosphorescence quenching measurements in
      microvessels.
AB  - Work by previous investigators has indicated that a substantial amount of oxygen
      diffuses from the precapillary circulation. These losses imply that there should
      be radial gradients of oxygen tension (PO(2)) in arterioles, leading to a non
      uniform distribution of oxygen within these microvessels. We have employed the
      phosphorescence quenching method to measure oxygen, allowing us to evaluate the
      heterogeneity of PO(2) inside short segments of microvessels. The phosphorescence
      decay curve contains information about the distribution of oxygen within the
      excited volume and the distribution can be represented as a histogram, by
      decomposing the decay curve into several components with weights proportional to
      the volume fraction of plasma with different PO(2), under the condition of a high
      signal-to-noise ratio. Furthermore, the histogram can be converted into a radial
      profile of PO(2), based on the assumptions of a circular vascular lumen,
      axisymmetric distribution of oxygen and monotonic PO(2) profile. Albumin-bound Pd
      porphyrin phosphor was infused into the circulation of hamsters and excited by
      flash illumination at 10 Hz, with a square region of excitation light just
      covering the entire lumen, (i.e. width of region equaled luminal diameter) of
      microvessels in the hamster mesentery. A set of 50 curves (5 s of data) was
      averaged to obtain a decay curve with low noise. Curves were analyzed with the
      above histogram procedure, and this analysis allowed us to distinguish between
      PO(2) values originating from intra and extravascular subvolumes. The
      intravascular PO(2) in these microvessels was very heterogeneous, which could be
      explained by the existence of significant radial PO(2) gradients. The radial
      PO(2) gradients were estimated to be approximately 1 mmHg/microm.

PMID- 12062207
TI  - Tumor PO(2) changes during photodynamic therapy depend upon photosensitizer type
      and time after injection.
AB  - In this study, the vascular and tissue oxygen changes induced by photodynamic
      therapy in the RIF-1 tumor were examined, using electron paramagnetic resonance
      (EPR) oximetry. Two photosensitizers, including verteporfin (BPD-MA in a lipid
      based formulation) and aminolevulinic acid-induced protoporphyrin IX (ALA-PPIX),
      were investigated with optical irradiation, sufficient to induce sub-curative
      damage in the tumor tissue, and the transient changes in PO(2) and vascular
      perfusion were examined. A large increase in tissue oxygenation (from 3 up to 9.5
      mmHg) was observed when treated with ALA-PPIX based photodynamic therapy, which
      lasted during the treatment and a small residual increase that returned back to
      baseline levels by 48 h after treatment. With verteporfin-based photodynamic
      therapy, one group of animals was irradiated 15 min after injection and exhibited
      a small decrease in oxygenation relative to pre-irradiation levels. The second
      group was irradiated at 3 h after injection and exhibited a large increase in the
      average PO(2), (from 3 to 15 mmHg) by the end of the treatment. These
      observations indicate that photodynamic therapy significantly increases tissue
      PO(2) under certain treatment conditions, with the potential cause being either
      increased local blood flow or decreased local oxygen metabolic consumption due to
      cellular damage.

PMID- 12062208
TI  - New artificial oxygen carriers made of pegulated polymerised pyridoxylated
      porcine haemoglobin (P(4)Hb).
AB  - Oxygen-carrying plasma expanders are designed for use as iso-oncotic 'blood
      substitutes' to combat oxygen deficiencies caused by blood loss. In contrast, a
      hypo-oncotic artificial oxygen carrier can be added to existing blood - as a
      'blood additive'. It has potential therapeutic use for deficiencies of oxygen
      which are not entailed by blood (volume) lack, and can therefore not be treated
      by a 'blood substitute', e.g. anaemias, local ischaemias and their complications
      such as stroke or myocardial infarction, or lack of oxygen in tumours, reducing
      the effectiveness of anti-cancer treatments by irradiation or chemotherapy. For
      such a novel approach haemoglobin-based oxygen-carrying additive, the haemoglobin
      must be highly polymerised in order to decrease the oncotic pressure, which can
      be received many times lower compared with smaller molecular size haemoglobins.
      Our aim is to produce haemoglobin polymers with narrow distributions of molecular
      weights of approximately 1,000,000 g/mol, preferably produced in high yield and
      at low cost. But polymerising haemoglobin by cross-linking normally results in a
      so-called percolation distribution of molecular weights, with a large amount of
      insoluble material, and with only poor yields of the desired polymers. A newly
      developed one-vessel synthesis procedure, which includes a controlled marked
      dilution of the synthesis medium during the cross-linking reaction, enables
      yields of polymerised haemoglobin (P(4)Hb) of over 80 %. Those preparations are
      easy and cheap to perform at large scales. P(4)Hb hyperpolymers (the high
      molecular moiety of P(4)Hb) are suitable for an oxygen-carrying blood additive:
      their oxygen-binding properties are sufficient, they are fully compatible with
      human blood plasma, and at the intended therapeutic concentration of
      approximately 30 g/l oncotic pressures are very low, and the impact on blood
      viscosity is tolerable.

PMID- 12062209
TI  - Immunomodulatory effect of oxygen and pressure.
AB  - The immunomodulatory effect of hyperbaric oxygen, involving altered cytokine
      release by macrophages, is well described. Importantly, however, it is not known
      what the relative contribution is of the hyperbaric environment of the cells vs.
      increased oxygen tension on these hyperbaric oxygen-dependent effects. We
      compared, therefore, cytokine release by murine macrophages under hyperbaric
      oxygen, hyperpressure of normal air and normobaric conditions. We observed that
      hyperbaric oxygen enhanced cytokine release of both unstimulated as well as
      lipopolysaccharide (LPS)-challenged macrophages. Hyperpressure of normal air,
      however, enhanced LPS-induced cytokine production but did not elicit cytokine
      release in unstimulated macrophages. To further investigate the molecular details
      underlying the effects of hyperbaric oxygen, we investigated the effect of the
      p42/p44 mitogen-activated protein (MAP) kinase inhibitor PD98059 and the p38 MAP
      kinase inhibitor SB203580. Neither inhibitor, however, had a significant effect
      on the modulatory effects of hyperbaric oxygen on cytokine release. We concluded
      that the immunomodulatory effect of hyperbaric oxygen contains a component for
      which hyperpressure is sufficient and a component that apart from hyperpressure
      also requires hyperoxygenation.

PMID- 12062210
TI  - Monitoring blood loss with near infrared spectroscopy.
AB  - Experimental research has shown correlation between near infrared spectroscopy
      (NIRS) and blood loss, but these findings have not been validated in man. Ten
      blood donors were monitored before, during and for 10 min after blood collection
      (470 ml) with NIRS. A Somanetics INVOS 4100 oximeter monitored regional
      haemoglobin saturation in the cerebral cortex (cSO(2)-left frontal area) and from
      the left calf (pSO(2)). A Critikon 2001 Cerebral Redox Model monitored total
      (tHb), oxygenated (O(2)Hb) and deoxygenated (HHb) haemoglobin from the right
      calf. The oxygenation index [HbD]=[O(2)Hb]-[HHb] was derived from the data.
      cSO(2) (P<0.001), pSO(2) (P<0.001) and HbD (P=0.001) decreased during blood
      collection. Maximum changes occurred 10 minutes after collection for cSO(2), with
      a mean fall (95% C.I.) of 2.5 (-0.06-4.86)%, at the end of blood collection for
      pSO(2), with a mean fall (95% C.I.) of 3 (0.74-5.26)% and after 8% of blood
      volume loss for HbD, with a mean fall (95% C.I.) of 7.2 (2.25-12.16). Cerebral
      and peripheral oxygenation did not recover after blood collection. There was good
      correlation between NIRS parameters and blood loss. NIRS is a potentially useful
      technique for monitoring blood loss in humans. Further research is needed to
      define its role in clinical practice.

PMID- 12062211
TI  - Stress-induced changes of plasma antioxidants in aquacultured sea bass,
      Dicentrarchus labrax.
AB  - Antioxidant plasma activities of ascorbate, alpha-tocopherol and glutathione
      peroxidase were analysed in adult male sea bass, Dicentrarchus labrax, in normal
      conditions and after hypoxia-recovery. In addition, tank measurements of
      temperature, pH, salinity and chlorine changes were carried out. Ascorbate and
      alpha-tocopherol were measured using a high-pressure liquid chromatography method
      and glutathione peroxidase activity enzymatically. Ascorbate and alpha-tocopherol
      showed a relationship with the velocity of body growing in normal and hypoxia
      recovery conditions. In sea bass exposed to hypoxia, only ascorbate and alpha
      tocopherol levels were significantly lower compared with the control group. Slope
      study and expression percent of antioxidants reduction after stress conditions
      revealed a predominant role of plasma alpha-tocopherol. Sea bass subjected to
      variations of salinity and chlorine showed a significant decrease in plasma alpha
      tocopherol. A relationship could be suggested between antioxidant defence and
      fish response in aquaculture.

PMID- 12062212
TI  - Chelator, metal ion and buffer studies for protein C separation.
AB  - Protein C (PC) is the pivotal anticoagulant and antithrombotic in the human
      coagulation cascade. PC deficiency can result in major medical problems such as
      deep vein thrombosis (DVT), leading to tissue oxygen deprivation. PC treatment
      has no bleeding or skin necrosis problems because it circulates in the blood as a
      zymogen and is only activated when and where it is needed. One source of PC is
      transgenic animal milk. The major components in the milk, such as alpha-casein,
      beta-casein, kappa-casein, alpha-lactalbumin and beta-lactoglobulin, are proteins
      that must be separated from PC. Immobilized metal affinity chromatography (IMAC)
      is an inexpensive separation technology with relatively high specificity, and it
      has great potential for difficult protein separations. After systematic studies
      of different chelator, metal ion and buffers, the combination of iminodiacetic
      acid (IDA) and Fe was found to be effective to separate PC from major milk
      components. alpha-Lactalbumin and beta-lactoglobulin fell through the column in
      the starting buffer. PC was eluted. alpha-Casein, beta-casein, kappa-casein
      remained bound in the column after PC elution. This technology might be applied
      for PC separation from transgenic animal milk. It is very important for PC
      production in large quantities and at low cost to treat PC-deficient patients.

PMID- 12062213
TI  - Cardiovascular and respiratory adjustments at altitude sustain cerebral oxygen
      delivery -- Severinghaus revisited.
AB  - Analysis of a paper by Severinghaus et al. (see text) has already shown that sea
      level oxygen delivery (D(a)O(2)) is sustained 8 h after ascent to 3810 m, despite
      low arterial oxygen content (C(a)O(2)), largely as a result of increased cerebral
      blood flow (CBF). The present study extends the analysis to show that D(a)O(2) is
      also sustained after 3 and 5 days at altitude, despite a progressively falling
      CBF. It is shown that this later compensation is a result of the improvement in
      C(a)O(2), which accompanies acclimatisation. Since less than 3% rise in
      haemoglobin occurred, the rise in C(a)O(2) was predominantly respiratory. It has
      been shown elsewhere that as acclimatisation occurs, the fall in arterial PCO(2)
      (P(a)CO(2)) results in increased arterial PO(2) (P(a)O(2)) until they are related
      according to P(a)CO(2)=0.25 P(a)O(2)+/-15 mmHg. The results from Severinghaus et
      al. at 3 and 5 days fall close to this line. We also report arterialised
      capillary blood gases from 18 normal subjects, acclimatised at 5300 m. The values
      fall in a group centred on the same line. In summary, soon after arrival at
      altitude (8 h), cerebral oxygen delivery is largely sustained by an increase in
      CBF. The present study shows that, although CBF declines during the 3-5 day
      period, D(a)O(2) is sustained as a result of the improvement in C(a)O(2), which
      is mainly due to respiratory acclimatisation.

PMID- 12062214
TI  - Sensing performance of protein C immuno-biosensor for biological samples and
      sensor minimization.
AB  - Protein C (PC) is an important anticoagulant and antithrombotic agent in human
      blood plasma. PC deficiency can result in clotting complications that interfere
      with oxygen and nutrient transport. A fiber-optic biosensor is being developed to
      provide real time diagnosis of PC deficiency. The PC sensor was tested to
      quantify PC level in human plasma. The signal intensity obtained from the plasma
      sample was 30% of the buffered sample, possibly due to the increased viscosity.
      The feasibility of monitoring PC level in animal cell culture broth and animal
      milk was tested. For the cell culture broth, 80% of signal was observed. However,
      the decrease was consistent over the sensing range. For whole and 1:100 diluted
      bovine milk, the signals were 60 and 78% of buffered sample, respectively. The
      biosensor length was reduced from 12.5 to 6 cm with sufficient sensitivity. To
      increase the sensor reusability, various elution buffers were applied after each
      sensing. Triethylamine elution buffer provided the best sensor regeneration
      capability and increased the number of assays from 2.5 to 7 times for 6 cm
      fibers.

PMID- 12062215
TI  - Effect of hypothermia on brain multi-parametric activities in normoxic and
      partially ischemic rats.
AB  - Hypothermia, as well as anesthesia, are known to protect the brain against
      ischemia, hypoxia and other pathological damages. One of the mechanisms of this
      improvement could be by lowering brain function, and thereby lowering oxygen
      demand. We examined the effect of hypothermia on brain function and blood supply
      in awake and anesthetized rats and studied the interaction between partial
      ischemia and the responses to hypothermia. The brain function multiprobe (BFM)
      used enabled simultaneous measurements of cerebral blood flow (CBF),
      mitochondrial NADH redox state, extracellular K(+) concentration, DC potential
      and ECoG from the cerebral cortex in rats whose brain temperature was lowered by
      5 degrees C. Hypothermia was induced in awake, anesthetized and brain ischemic
      anesthetized rats. In anesthetized and ischemic-anesthetized rats, the time
      required for lowering the brain temperature by 5 degrees C was five times less
      than in the normal awake animals. No significant changes in CBF and NADH levels
      were found in response to hypothermia in the awake animals. In contrast, a
      significant decrease in extracellular K(+) concentration was recorded under
      hypothermia, probably due to the lower rate of depolarization. Hypothermia in
      anesthetized and in ischemic-anesthetized rats did not significantly affect the
      levels of mitochondrial NADH, CBF and extracellular K(+). Hypothermia under
      ischemia was expected to be more effective.

PMID- 12062216
TI  - HSP47 expression in cornea after excimer laser photoablation.
AB  - PURPOSE: The expression of heat shock protein 47 (HSP47) was observed
      histologically to investigate the spatial and chronological effects of excimer
      laser photoablation. HSP47 expression after radial keratotomy (RK) was also
      investigated and compared with the effects after excimer laser photoablation.
      METHOD: Twenty-eight male rabbits were used. The rabbits were divided with two
      groups and treated with either excimer laser photoablation or four radial
      incisions to simulate corneal refractive surgery. The chronological and spatial
      changes in the expression of HSP47 were observed immunohistochemically. RESULTS:
      In eyes that underwent excimer laser photoablation, HSP47 was detected in the
      basal layer of the epithelial cells and in the superficial stromal layer 3 days
      after surgery. After 5 and 7 days, HSP47 expression extended to the deep layer of
      the stroma and to the endothelial cells. After 14 days, HSP47 was detected only
      in the deep layer of the stroma and in the endothelial cells. After 28 days,
      HSP47 expression was reduced. In eyes that underwent RK, HSP47 was detected in
      the basal layer of the epithelial cells and in the stroma surrounding the wound 1
      day after surgery. After 3 and 7 days, HSP47 expression did not expand further.
      After 28 days, HSP47 expression diminished. CONCLUSIONS: Excimer laser
      photoablation affects the whole layer of the cornea, and may be caused by the
      shock wave that occurs as a result of photoablation. In addition, interaction
      among the keratocytes may propagate the stress-induced response to the whole
      layer of the cornea. With RK, the wound is smaller and deeper. HSP47 expression
      occurs earlier, but is limited to the area surrounding the wound.

PMID- 12062217
TI  - Corneal disorders in KKAy mouse: a type 2 diabetes model.
AB  - PURPOSE: To observe the clinical and histopathological changes occurring in
      corneas of KKAy mice, a model of type 2 diabetes, and to elucidate the possible
      mechanisms involved in these changes. METHODS: Corneal epithelial cell
      proliferation was analyzed in KKAy and age-matched non-diabetic C57BL/6J control
      mice using (3)H-thymidine autoradiography. Clinical examination and
      histopathological analysis were also conducted on both types of mice. RESULTS:
      KKAy mice showed a significant elevation in blood glucose concentration and body
      weight compared to age-matched control mice. Fragile corneal epithelial cell
      attachment and subepithelial opacities were observed in the central area of the
      cornea of 10-week-old KKAy mice. Corneal epithelial cell proliferation decreased
      significantly in the 16-week-old KKAy mice. Histological study in the older KKAy
      mice groups revealed the presence of subepithelial deposits, widening of the
      intracellular spaces between corneal epithelial cells with poor adherence to the
      basement membrane (BM) and thickening of the BM itself. At the central area of
      the cornea, remnants of cell components with deposits and lacuna formation were
      observed, perhaps secondary to the continuous presence of poor adhesion and
      detachment of epithelial cells in the area. In the 50-week and older KKAy mice,
      thinning and atrophy of the corneal epithelial cell layer became more prominent
      at the central cornea with increases in deposition of materials, blood vessel
      invasion and activation of keratocytes. The deposits were stained black by von
      Kossa's method, indicating the presence of tissue calcium. Type IV collagen
      immunoreactivity was observed not only in the corneal and conjunctival BM but
      also between the stroma, particularly around the central cornea and in the walls
      of invading vessels. Laminin staining was intense at the BM around the central
      cornea, and in the walls of invading vessels along the stroma. Pyrraline, which
      is one of the major components of advanced glycation end products, was also
      present in the stroma, and around blood vessels. All these corneal changes were
      not observed with aging in the age-matched C57BL/6J mice. CONCLUSIONS: Our
      findings provide evidence of the existence of corneal disorders in KKAy mice.
      These observations may provide useful information for the explanation of the
      mechanisms involved in corneal disorders in non-insulin-dependent diabetes
      mellitus patients.

PMID- 12062218
TI  - Transferrin-polyethylenimine conjugate, FuGENE6 and TransIT-LT as nonviral
      vectors for gene transfer to the corneal endothelium.
AB  - PURPOSE: To investigate the efficacy and pathogenicity of three commercially
      available nonviral DNA vectors for gene transfer to the corneal endothelium.
      METHODS: Corneas obtained from New Zealand White rabbits were cultured ex vivo.
      For cell culture, the corneal endothelial cells were removed and cultured in
      vitro under standard conditions. Using the vectors, culture cells or ex vivo
      corneas were transfected with plasmid DNA coding for green fluorescent protein
      (GFP). Expression of the transduced gene was monitored by fluorescence
      microscopy. Transfection efficiency was estimated as the percentage of GFP
      positive cells identified. The viability and morphology of the endothelium were
      also examined. RESULTS: Transferrin-polyethylenimine conjugate was effective in
      vitro but not ex vivo. FuGENE6 and TransIT-LT mediated the transfer of GFP gene
      both in in vitro and in ex vivo culture. Their efficiency estimated at day 3 was
      28.8% and 38.8% in vitro, and 8.1% and 8.8% ex vivo, respectively. Viability
      staining revealed no dead cells. Morphological study showed no apparent
      alteration. CONCLUSIONS: FuGENE6 and TransIT-LT are safe, simple to use, and may
      be useful alternative methods for gene transfer to the corneal endothelium,
      avoiding certain side effects of viral vectors. As the efficiency could be
      enhanced, these nonviral vectors may be promising for practical application.

PMID- 12062219
TI  - Cellular fibronectin, but not collagens, disappears in the central posterior
      capsules during healing after lens extraction and IOL implantation in rabbits.
AB  - PURPOSE: To investigate the nature of capsular opacification after cataract
      intraocular lens (IOL) surgery in rabbit eyes, we immunohistochemically located
      extracellular matrix components in lens capsules after the surgery using light
      microscopy. The study was conducted also to compare the extracellular matrix
      components in rabbit capsules with those previously reported in the human eye.
      METHODS: Twenty-seven eyes of 17 Japanese albino rabbits were lensectomized by
      phacoemulsification, and IOLs were implanted. Using immunohistochemical methods,
      the lens capsules were examined immediately after surgery, and 1, 2, 4, and 8
      weeks after surgery. RESULTS: In all cases at each time point, the edge of the
      anterior capsulotomy had contracted and was found to adhere to the inner surface
      of the posterior capsule, with both IOL haptics remaining in the capsular bag.
      Collagen types I and III were detected around the adhesion between the anterior
      capsulotomy edge and posterior capsule during all stages of healing and also
      observed on the central posterior capsules 1 or more weeks after surgery.
      Immunoreactivity for cellular fibronectin was seen around the adhesion between
      the anterior capsulotomy edge and posterior capsule during all stages of healing.
      It was also detected on the posterior capsules 2 and 4 weeks after surgery, but
      disappeared 8 weeks after surgery. CONCLUSION: Extracellular matrix components
      such as collagen types I and III and cellular fibronectin were expressed inside
      the residual lens capsular bag. Cellular fibronectin may play a role in the early
      wound healing process in the postoperative posterior capsule because the
      immunoreactivity in the central posterior capsule disappears in the later phase
      of healing.

PMID- 12062220
TI  - Effects of a new excitotoxic amino acid, dysiherbaine, on cultured Muller cells.
AB  - PURPOSE: To determine the pharmacological response when dysiherbaine acts on
      cultured Muller cells, considering the glutamate receptor functions. Dysiherbaine
      is a new excitotoxic amino acid, which was recently isolated from the liquid
      extract of a certain sponge. METHODS: Retinas of adult rabbits were used to
      culture the Muller cells. Intracellular calcium ion concentration ([Ca(2+)](i))
      analysis was done by fluorophotometry with the calcium indicator, acetoxymethyl
      ester fura-2 (Fura-2 AM). RESULTS: A transient increase of [Ca(2+)](i) was
      observed following the administration of dysiherbaine (2.5 microM-2.5 mM) to
      Muller cells, but no [Ca(2+)](i) increase was observed in the extracellular
      calcium-free solution. This increase was blocked by the non-N-methyl-D-aspartate
      (NMDA) glutamate receptor antagonist, 6-cyano-7 nitroquinoxaline-2,3-dione
      (CNQX). A dysiherbaine-induced increase in [Ca(2+)](i) following preincubation of
      the NMDA glutamate receptor antagonist, (5R,10S)-(+)-5-methyl-10,11-dyhydro-5H
      dibenzo [a,d] cyclohepten-5, 10-imine hydrogen maleate (MK 801) was seen in the
      same number of Muller cells with and without the antagonist. CONCLUSIONS:
      Dysiherbaine appears to act primarily as a non-NMDA glutamate receptor agonist,
      having a secondary action as a NMDA glutamate receptor agonist.

PMID- 12062221
TI  - Effects of local administration of interferon-beta on proliferation of retinal
      pigment epithelium in rabbit after laser photocoagulation.
AB  - PURPOSE: To investigate whether local administration of interferon (IFN)-beta
      promotes proliferation of the retinal pigment epithelium (RPE) in vivo. METHODS:
      Following local injection of IFN-beta into the sub-Tenon space of rabbit eyes,
      the penetration of IFN-beta into various intraocular areas was determined by
      means of enzyme-linked immuno-adsorbent assay. Retinal lesions were produced by
      laser photocoagulation (PC), and IFN-beta (1 x 10(6) IU, 1 x 10(5) IU, or 1 x
      10(4) IU) was administered into the sub-Tenon space. Physiological saline was
      substituted for IFN-beta in controls. The proliferation of RPE cells was
      inspected histopathologically. RESULTS: After IFN-beta administration, IFN-beta
      was found in all intraocular areas examined, with the highest concentration
      detected in the choroid. After PC, profuse proliferation of RPE cells began
      earlier in the rabbits that received the highest dose of IFN-beta than in the
      control rabbits; repair of the central part of the coagulated lesion in those
      rabbits was complete within 7 days after PC. In control rabbits, the
      histopathologic wound repair process proceeded more slowly and to a limited
      extent. Proliferation of RPE cells in the low and medium dose IFN-beta-treated
      rabbits was similar to that in the control rabbits. CONCLUSION: The present study
      demonstrates that repair of the PC-induced retinal lesions, particularly the
      proliferation of RPE cells, is promoted in vivo by local administration of IFN
      beta.

PMID- 12062222
TI  - Effects of caffeine on microcirculation of the human ocular fundus.
AB  - PURPOSE: To determine the effect of caffeine on microcirculation in the human
      ocular fundus. METHODS: The microcirculation in the ocular fundus of 10 healthy
      volunteers (10 eyes) was studied using a laser speckle tissue circulation
      analyzer. Caffeine or placebo (100 mg) was administered orally in a double-masked
      manner. Square blur rate (SBR), a quantitative index of blood flow velocity, was
      measured in a temporal site of the optic nerve head (ONH) free of surface vessels
      and in a middle site of the choroid-retina between the ONH and macula.
      Intraocular pressure (IOP), blood pressure (BP), pulse rate (PR), and central
      critical fusion frequency (CFF) were also measured. These parameters were
      measured before and for 2 hours after administration. The area under curve (AUC)
      of SBR was calculated for each area. Ocular perfusion pressure (OPP) was also
      calculated from BP and IOP. RESULTS: The time-course of change in SBR value
      showed much individual difference. Caffeine decreased the AUC of SBR in the ONH
      (P =.0218) as well as in the choroid-retina (P =.0469) significantly. IOP, mean
      BP, PR, OPP, and central CFF did not change significantly. CONCLUSIONS: These
      results suggest that caffeine may increase blood vessel resistance and decrease
      blood flow in the human ONH and choroid-retina.

PMID- 12062223
TI  - Dacryocystorhinostomy for dacryocystitis caused by methicillin- resistant
      Staphylococcus aureus: report of four cases.
AB  - BACKGROUND: To evaluate the outcome of dacryocystorhinostomy (DCR) for
      dacryocystitis caused by methicillin-resistant Staphylococcus aureus (MRSA).
      CASES: Four otherwise healthy patients with dacryocystitis caused by MRSA were
      studied (3 with chronic dacryocystitis; 1, acute dacryocystitis). Ophthalmic
      symptoms were epiphora with purulent discharge in 2 cases, with
      blepharoconjunctivitis in 1 case, and with lacrimal fistula in 1 case. Culture of
      the purulent discharge from the affected conjunctival sacs revealed MRSA
      infection. Initial treatment, which was unsuccessful, included intravenously
      administered common antibiotics, the use of topical antibiotics and povidone
      iodine in the conjunctival sac and mupirocin ointment in the nasal cavity.
      Subsequently, standard DCR was performed with a bicanalicular silicone tube
      inserted under local anesthesia, accompanied by the administration of common
      antibiotics. OBSERVATION: Cultures from all patients were negative for MRSA as
      soon as 4 days after DCR. None of the patients had epiphora with pus, and the
      lacrimal passage became patent postoperatively. CONCLUSION: Dacryocystitis due to
      MRSA was resistant to conservative therapy. DCR subsequent to the conservative
      therapy resulted in almost immediate resolution of the lacrimal fistula and
      nasolacrimal obstruction, rapid control of dacryocystitis, and a decrease in the
      period of MRSA infection in the conjunctiva and the nasal cavity.

PMID- 12062224
TI  - External dacryocystorhinostomy combined with mucosal grafting and magnetic
      resonance imaging.
AB  - PURPOSE: To facilitate understanding of the use of magnetic resonance imaging
      (MRI) in nasolacrimal obstructive diseases and to determine the indication for
      external dacryocystorhinostomy (DCR) combined with mucosal grafting. METHODS: We
      retrospectively studied the correlation between MRI images and surgical findings
      in 13 consecutive patients with swollen lacrimal sacs because of obstruction of
      the nasolacrimal duct or lacrimal sac. They were treated at the Kagoshima
      University Hospital between June 1999 and May 2001. RESULTS: A simple procedure
      of external DCR was performed in 9 cases, and a procedure combined with mucosal
      grafting was performed in 4 cases (age range, 51-88 years). Surgical findings in
      the fibrous region of the lacrimal sac corresponded to the hyperintense signal on
      MRI T(1)-weighted (T1W) images, more remarkably after enhancement. Surgical
      findings in the granulomatous sac and proteinaceous contents corresponded to the
      isointense areas on T2W images. Cases with thin sac were treated by standard DCR,
      whereas cases with thick, fibrous and granulomatous sac were treated by external
      DCR combined with mucosal grafting. CONCLUSIONS: The MRI images provide a useful
      preoperative determination for indications of external DCR combined with mucosal
      grafting.

PMID- 12062225
TI  - Corneal endothelial cell changes twenty years after penetrating keratoplasty.
AB  - PURPOSE: To evaluate retrospectively the corneal endothelium in 15 eyes which
      showed clear cornea for 20 years or longer after penetrating keratoplasty.
      METHODS: The corneal endothelium was investigated in 15 eyes. The causative
      lesion had been keratoconus in 10 eyes and herpetic keratitis in 5 eyes. At the
      time of surgery, the patients were aged from 6 to 45 years, average 25.3 +/- 10.4
      years. The endothelial cell density was measured 10 and 20 years after surgery by
      specular microscope. The relation between the rate of endothelial cell density
      loss and postoperative graft rejection, final visual acuity, causative corneal
      lesion, age of the patient, and age of the donor was evaluated. RESULTS: The
      endothelial cell population per mm(2) averaged 998 +/- 343 ten years after
      surgery and 852 +/- 245 twenty years after surgery. The rate of endothelial cell
      density loss thus averaged 12.1% +/- 16.3% during the last 10 years. This rate
      was independent of postoperative graft rejection, final visual acuity, causative
      corneal lesion, age of the patient, or age of the donor. CONCLUSIONS: The corneal
      endothelial cells become stabilized 10 years after surgery in cases where the
      grafts remain transparent 20 years after surgery.

PMID- 12062226
TI  - Corneal myxoma.
AB  - BACKGROUND: Myxomas are rare benign tumors that can be found most frequently in
      the heart. We report the clinical and histological findings in a very rare case
      of corneal myxoma, which is only the sixth case in the literature. CASE: A
      whitish elevated tumor of the anterior cornea developed in the left eye cornea of
      a 46-year-old man 2 years after luxation of the patient's lens into the anterior
      chamber and subsequent endothelial decompensation. The tumor covered the entire
      surface of the cornea except for the outer limbal periphery at Schwalbe's line.
      OBSERVATIONS: Histologically, the hypocellular tumor was characterized by
      scattered spindle- and stellate-shaped cells with wavy, randomly oriented
      collagen fibers in a myxomatous ground substance staining positively for acid
      mucopolysaccharides. Bowman's layer was absent. Immunohistochemically, the tumor
      cells were positive for vimentin. Ultrastructurally, the tumor cells had features
      characteristic of keratocytes with no basement membrane, much rough endoplasmic
      reticulum and vacuoles containing mucoid-like material. CONCLUSIONS: The
      ultrastructural observations support the hypothesis of a cellular origin of the
      myxoma from keratocytes. The tumor growth was most probably stimulated by chronic
      endothelial failure and bullous keratopathy.

PMID- 12062227
TI  - Neovascular glaucoma associated with cilioretinal artery occlusion combined with
      perfused central retinal vein occlusion.
AB  - BACKGROUND: Cilioretinal artery occlusion rarely results in neovascular glaucoma,
      especially in cases of extensive cilioretinal infarction and combined retinal
      vascular occlusion. CASE: A 62-year-old man with diabetes mellitus and essential
      hypertension showed a visual acuity of counting fingers, retinal whitening
      temporal to the optic disc with mild dilation and tortuosity of the retinal
      veins, and retinal hemorrhages in four quadrants of his right eye. Fluorescein
      angiography demonstrated a delayed filling of the central retinal vein and
      cilioretinal artery. OBSERVATIONS: Two months later, neovascular glaucoma
      developed and retinal ablation was performed using an argon laser. Trabeculectomy
      was also performed due to the intractability of the glaucoma, and central artery
      occlusion was found. On magnetic resonance angiography, the right distal common
      carotid artery was irregularly narrowed and the right ophthalmic artery was
      almost entirely occluded. CONCLUSIONS: In cases of cilioretinal artery occlusion
      and perfused central retinal vein occlusion with multiple risk factors, close
      follow-up is advised.

PMID- 12062228
TI  - Aqueous humor adrenomedullin levels differ in patients with different types of
      glaucoma.
AB  - PURPOSE: Adrenomedullin is a multifunctional 52 amino acid large peptide. Recent
      studies have reported that it is expressed in the iris-ciliary body in the eye
      and that it decreases intraocular pressure (IOP) by increasing outflow facility
      via specific adrenomedullin receptors, suggesting a role for this peptide in
      controlling IOP. In the present study, we aimed to explore clinically the
      possible involvement of adrenomedullin in the pathophysiology of glaucoma.
      METHODS: Reverse-phase high-performance liquid chromatography was used to
      determine the aqueous humor adrenomedullin levels in 41 patients (41 eyes)
      undergoing elective surgery for a variety of ocular diseases in the Research
      Hospital of Inonu University Medical Faculty between 1999 and 2000. The ocular
      diseases of the patients included primary open-angle glaucoma (POAG, n = 16),
      neovascular glaucoma (NG, n = 11), and cataract (n = 14). The study was an open
      trial with purposive sampling. Aqueous humor samples were taken by paracentesis.
      Mann-Whitney U-test was used in the statistical analysis and P <.05 was
      considered as significant. Results were expressed as mean +/- SE. RESULTS: The
      mean age and sex distribution between groups were comparable. Mean adrenomedullin
      levels in patients with POAG (22.3 +/- 0.6 pmol/L) were significantly higher than
      those in patients with NG (5.6 +/- 0.2, pmol/L; P <.001) and cataract (11.9 +/-
      0.5, pmol/L; P <.001). On the other hand, the mean aqueous humor adrenomedullin
      levels in patients with NG were significantly (P <.001) lower than those in
      cataract patients. CONCLUSIONS: This first clinical in vivo study on aqueous
      humor adrenomedullin levels showed that this peptide may be involved in the
      pathophysiology of glaucoma. Increased aqueous humor adrenomedullin levels in
      patients with POAG may indicate a compensatory defense response against increased
      IOP to slow the formation and progression of a vicious cycle. On the other hand,
      there may be deficient production of the peptide in patients with NG, or
      adrenomedullin-producing cells may be lost because of very high IOP during the
      course of the disease. The control of adrenomedullin levels in the eye might be a
      target that could be considered in the therapeutic strategies for glaucoma.
      Further studies in this respect are needed.

PMID- 12062229
TI  - Retinal vascular obstruction and asymptomatic cerebral infarction.
AB  - PURPOSE: The purpose of this study is to clarify the relationship between retinal
      vascular obstruction and asymptomatic cerebral infarction (ACI). METHODS: Forty
      three patients (27 men and 16 women) with retinal vascular obstruction were
      examined by magnetic resonance imaging (MRI) at the Department of Ophthalmology
      of Nagasaki University Hospital in Nagasaki, Japan. Patients with a history of
      neurological signs and symptoms were excluded from this study. The control group
      consisted of 93 male and 49 female patients who were examined by MRI for routine
      brain screening examinations at the Takaki Neurosurgical Clinic in Fukuoka,
      Japan. We investigated the incidence of ACI, and the risk factors and
      characteristics of this condition. RESULTS: ACI was more common in patients with
      retinal vascular obstruction than in normal adults at all ages. The incidence of
      hypertension in the patients with ACI tended to be higher than in the patients
      without ACI. CONCLUSION: ACI appears more frequently in patients with retinal
      vascular obstruction than in normal adults. Our results indicate that either
      retinal artery occlusion or retinal vein occlusion should be considered a sign of
      ACI and systemic diseases such as arteriosclerosis.

PMID- 12062230
TI  - Successful management of conjunctival intraepithelial neoplasia by interferon
      alpha-2b.
AB  - BACKGROUND: Interferon alpha-2b (IFN alpha 2b) was recently shown to be effective
      as an alternative therapy for conjunctival intraepithelial neoplasia (CIN).
      Herein, we report our successful management of CIN by the use of IFN alpha 2b.
      CASE: A 73-year-old woman presented with a complaint of irritation due to a
      tumorous lesion in her left eye. Slit-lamp microscope examination revealed a
      tumorous lesion involving the bulbar and palpebral conjunctiva as well as the
      limbus, from the 3-o'clock position to the 8-o'clock position. She had already
      undergone cryotherapy in the same eye in another hospital, twice for a lesion on
      the lower tarsal conjunctiva and once for a lesion on the upper tarsal
      conjunctiva. The histological diagnosis had been CIN. OBSERVATIONS: In treating
      this patient, IFN alpha 2b was injected subconjunctivally twice and also applied
      as eye drops for 12 weeks. Two weeks after the initial treatment, the tumorous
      lesion disappeared. During a 1-year follow-up period, no recurrence was noted.
      CONCLUSION: Topical and subconjunctival IFN alpha 2b is a valuable treatment
      option for CIN.

PMID- 12062231
TI  - Monocyte chemotactic protein-1 levels in the vitreous of patients with
      proliferative vitreoretinopathy.
AB  - PURPOSE: To assess the potential role of monocyte chemotactic protein-1 (MCP-1)
      in the pathogenesis of proliferative vitreoretinopathy (PVR) and to investigate
      its possible interaction with the macrophage migration inhibitory factor (MIF).
      METHODS: We assayed MCP-1 and MIF levels in the vitreous samples of 85
      consecutive patients with PVR (29 eyes), rhegmatogenous retinal detachment (RRD;
      22 eyes), and macular hole or idiopathic epimacular membrane (controls; 34 eyes),
      by enzyme-linked immunosorbent assay. RESULTS: Vitreous levels of MCP-1 were
      1760.7 +/- 471.3 pg/mL (mean +/- SD) in PVR patients, 1200.4 +/- 579.8 pg/mL in
      RRD patients, and 436.3 +/- 286.1 pg/mL in the controls. Vitreous MCP-1 levels in
      PVR patients were significantly higher than those in RRD patients and in the
      controls (P <.0001, respectively). MCP-1 levels in grade C of PVR (1883.7 +/-
      479.5 pg/mL) were significantly greater than those in grade D (1437.8 +/- 258.8
      pg/mL) (P =.0112). Vitreous concentrations of MCP-1 had no correlation with those
      of MIF. CONCLUSIONS: The results indicate the possibility that MCP-1 may have a
      role mainly in the early stage of PVR and that the role of MCP-1 in PVR may
      differ from that of MIF.

PMID- 12062232
TI  - Persistent intraschisis hemorrhage simulating choroidal melanoma.
AB  - BACKGROUND: Intraschisis hemorrhage of dark green color without accompanying
      vitreous hemorrhage is a rare complication of degenerative retinoschisis
      detachment. CASE: A 37-year-old male patient with unilateral intraschisis
      hemorrhage closely mimicking a choroidal melanoma is described. OBSERVATIONS:
      Ultrasonography and intravenous fluorescein angiography suggested intraschisis
      hemorrhage. T(1)-weighted magnetic resonance imaging demonstrated a hyperintense
      lesion compared to the vitreous that did not enhance with contrast agent. Managed
      by observation, the color of the lesion started to change at the 6th month of
      follow-up. The hemorrhagic lesion regressed to half size in 40 months following
      the diagnosis, and disappeared in 62 months. CONCLUSION: Very rarely may an
      intraschisis hemorrhage secondary to degenerative retinoschisis-detachment
      simulate a choroidal melanoma. In our patient, careful interpretation of the
      conventional methods was adequate for the differential diagnosis. The unusual
      feature of this patient was that the hemorrhage resolved in 5 years, much slower
      than expected.

PMID- 12062233
TI  - Modulation of insulin-like growth factor-I production of cultured retinal
      vascular endothelial cells by oxygen, glucose and growth hormone.
AB  - PURPOSE: To evaluate the interaction of oxygen, glucose, and growth hormone (GH)
      on insulin-like growth factor-I (IGF-I) production of cultured bovine retinal
      vascular endothelial cells. METHODS: Confluent cultures of bovine retinal
      vascular endothelial cells were incubated under 3% or 20% oxygen in Dulbecco's
      modified Eagle's medium (containing 1 g/L or 4.5 g/L glucose), with or without
      the addition of 10 ng/mL GH. After incubation times of 0, 24, 48, and 72 hours,
      IGF-I was measured in the supernatant, and cells were counted. RESULTS: Highest
      levels of IGF-I were reached after 72 hours with 4.5 g/L glucose and 10 ng/mL GH
      under 3% O(2). All IGF-I levels found in 3% O(2) samples were significantly
      higher than those found in 20% O(2) samples. No statistical significance was
      found regarding glucose concentration or GH supplement. CONCLUSIONS: Oxygen
      turned out to be the sole modulating factor for IGF-I production of cultured
      retinal vascular endothelial cells.

PMID- 12062251
TI  - Muscular dystrophy into the new millennium.
AB  - Since the identification of the gene for Duchenne muscular dystrophy and its
      protein product some 15 years ago, the basic defects in all the commoner forms of
      dystrophy have now been identified. It is thus possible, on the basis of this
      information, to make a precise diagnosis in an affected individual and to offer
      accurate genetic counselling and prenatal diagnosis. Now newer technologies are
      being applied to the investigation of these disorders. These include studies of
      single nucleotide polymorphisms, microarray analysis and expression profiling,
      the yeast two-hybrid assay, and proteomics. A great deal of new information is
      emerging in this way which will hopefully help us to understand the causes of
      inter-familial and intra-familial variation and particularly pathogenesis, a
      detailed understanding of which could be the first step in finding effective
      treatments.

PMID- 12062253
TI  - Absence of hearing impairment in adult onset facioscapulohumeral muscular
      dystrophy.
AB  - Hearing impairment has long been associated with the rarer forms of severe
      childhood and infantile facioscapulohumeral muscular dystrophy. Recent studies
      have suggested a high prevalence in classic, adult or adolescent, onset cases as
      well. We undertook detailed pure tone audiometric examination of 21 adult onset
      facioscapulohumeral muscular dystrophy cases. Patient results were compared with
      normative data obtained from the (United Kingdom) National Study of Hearing (The
      prevalence and distribution of hearing impairment and reported hearing disability
      in the MRC Institute of Hearing Research's National Study of Hearing, Whurr,
      1995). There was no significant difference in the prevalence of hearing
      impairment in facioscapulohumeral muscular dystrophy patients at any single or
      averaged frequency tested. In this group of patients, pure tone audiometric
      thresholds were consistently better in the facioscapulohumeral muscular dystrophy
      patients, although these reached statistical significance only at 4 and 6 kHz.
      Age of onset, disease duration, clinical severity, degree of facial weakness and
      double-digest fragment size made no significant difference to mean hearing
      thresholds. We conclude that hearing impairment is not more common in adult onset
      facioscapulohumeral muscular dystrophy, and according to this data, may even, be
      less prevalent than in the normal population.

PMID- 12062252
TI  - Early onset chromosome 14-linked distal myopathy (Laing).
AB  - A dominantly inherited form of distal myopathy with onset in early childhood was
      first reported in a 4-generation Australian family in 1995. In the present report
      we provide further information on the clinical phenotype and natural history of
      this myopathy, and on the electromyogram and magnetic resonance imaging findings
      in affected individuals. The pattern of muscle involvement was similar to that in
      the 'tibial' forms of distal myopathy such as the Finnish (Udd) and Markesbery
      Griggs types, with additional involvement of the finger extensors and of some
      more proximal limb and neck muscles. However, the age of onset was earlier than
      in these other myopathies and rimmed vacuoles were not found in biopsies from two
      affected individuals. Evidence of possible anticipation was found in one branch
      of the family. The gene locus for this myopathy had been mapped to 14q11.2-q13.
      The linkage region has been refined to a 24 cM region between D14S283 and D14S49
      and mutations have been excluded in the PABP2 gene for oculopharyngeal muscular
      dystrophy which lies within this region.

PMID- 12062254
TI  - DMD(mdx3Cv) and DMD(mdx4Cv) dystrophin mutations in mice: rapid polymerase chain
      reaction genotyping.
AB  - We devised non-radioactive PCR assays for the DMD(mdx3Cv) and DMD(mdx4Cv) mouse
      dystrophin point mutations, in which mutant and wild type reactions
      electrophoresed separately diagnose whether the DNA carries the mutant, wild
      type, or both alleles. This simple and reliable assay facilitates the use of
      these mutant mouse models, which have an extended inflammatory phase
      (DMD(mdx3Cv)), less reversion to wild type (DMD(mdx4Cv)), and reduced expression
      of dystrophin mRNAs arising from internal promoter usage than the DMD(mdx) mouse.
      The PCR assays described facilitate the use of the DMD(mdx3Cv) and DMD(mdx4Cv)
      mutant mouse models, when maintaining the mutations as heterozygotes,
      backcrossing into different inbred genetic backgrounds, or when crossing targeted
      mutations into these dystrophic backgrounds.

PMID- 12062256
TI  - Spinal muscular atrophy among the Roma (Gypsies) in Bulgaria and Hungary.
AB  - Spinal muscular atrophy is one of the most common autosomal recessive disorders,
      classified into three major clinical forms. It is caused mainly by deletions or
      gene conversions of the telomeric survival motor neuron gene (SMN1) on human
      chromosome 5. We have conducted molecular studies of the disorder in genetically
      isolated Romani (Gypsy) communities in Bulgaria and Hungary, where spinal
      muscular atrophy appears to have different prevalence and both mild and severe
      spinal muscular atrophy phenotypes have been diagnosed. We have observed three
      distinct genetic defects which, in different combinations, lead to different
      forms of the disease. The similar chromosomal background on which the different
      mutations occur suggests a common origin and founder effect, with rearrangements
      of a single ancestral chromosome resulting in a diversity of molecular defects.

PMID- 12062255
TI  - Overexpression of dystrobrevin delays locomotion defects and muscle degeneration
      in a dystrophin-deficient Caenorhabditis elegans.
AB  - Duchenne muscular dystrophy is one of the most common neuromuscular diseases. It
      is caused by mutations in the dystrophin gene. Dystrobrevins are dystrophin
      associated proteins potentially involved in signal transduction. The nematode
      Caenorhabditis elegans possesses one dystrophin-like (dys-1) and one dystrobrevin
      like (dyb-1) gene. Mutations of dyb-1 and dys-1 lead to similar phenotypes,
      comprising hyperactivity and a tendency to hypercontract, which suggest that
      these proteins may participate in a common function. We show here that
      overexpression of the Dyb-1 protein delays the onset of the myopathy observed in
      the C. elegans double mutant (dys-1; hlh-1 mutations). This finding indicates
      that, in C. elegans, (1) the absence of dystrophin can be partly compensated for
      by extra doses of dystrobrevin, and (2) dystrobrevin is partly functional in
      absence of dystrophin.

PMID- 12062257
TI  - Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe's
      disease.
AB  - We describe three brothers suffering from Krabbe's disease with onset in the
      fifth decade. The proband showed a complete deficiency of leukocyte enzyme
      galactocerebrosidase and was found to be heterozygous for two previously
      described mutations: G > A809 and 502T/del consisting of a 30 kb deletion. In all
      three brothers the neurological examination showed features of asymmetrical
      peripheral neuropathy associated with pyramidal signs and the
      electrophysiological examination showed a generalized slowing of nerve conduction
      velocities. Two patients died at 59 and 61 years of age due to respiratory
      failure. Both the proband and his brother underwent a sural nerve biopsy. In the
      former the most striking finding was the presence of uniformly thin myelin
      sheaths without evidence of demyelination; a complete absence of fibers was found
      in the latter. Our findings confirm that peripheral neuropathy may be the
      presenting feature of late-onset Krabbe's disease. Hypomyelination rather than
      demyelination may represent the distinguishing pathological finding of this
      condition.

PMID- 12062258
TI  - Hypermyelinating neuropathy, mental retardation and epilepsy in a case of merosin
      deficiency.
AB  - Children with a deficiency of laminin alpha 2 chain generally show an involvement
      of skeletal muscles, cerebral white matter and peripheral nerves. Among these
      patients, however, there is increasing evidence of molecular and phenotype
      heterogeneity. We report a 19-year-old girl with distal weakness, mental
      retardation and refractory epilepsy in whom elevated serum CK suggested a
      myopathy. Electrophysiological and neuroimaging examinations as well as studies
      of nerve and muscle biopsies were performed. Nerve conduction velocities were
      definitely reduced and brain MRI demonstrated a diffuse white matter involvement.
      The muscle biopsy showed both myopathic and neurogenic features. By
      immunohistochemistry laminin alpha 2 chain was mildly reduced in muscle and
      virtually absent in peripheral nerve. Teasing of sural nerve fibers showed a
      'globular' hypermyelination characteristically located at the paranodal regions.
      A mild loss of myelinated fibers without any demyelination-remyelination changes
      was found. Haplotype analysis suggested linkage to the LAMA2 locus. Our case is
      peculiar as the putative mutation probably affects the expression of laminin
      alpha 2 chain is affected in a tissue specific manner: the protein is virtually
      absent in peripheral nerves but only mildly reduced in skeletal muscle. As to the
      disorder of nerve myelination, an absence or abnormal functioning of laminin
      alpha 2 chain can alter the feed-back control during myelinogenesis, leading to
      an over-ensheathment of axon. Alternatively, a compensatory up-regulation of
      other laminins can induce the hyperproduction of myelin sheaths. This case
      provides new evidence of the phenotypical heterogeneity of the LAMA2 gene and
      sheds light in understanding the role of laminin alpha 2 chain in myelination of
      peripheral nerve.

PMID- 12062260
TI  - Immune mechanisms in acquired demyelinating neuropathies: lessons from animal
      models.
AB  - The peripheral nervous system (PNS) is the target for a heterogenous immune
      attack mediated by T-cells, B-cells, and macrophages. The interaction of the
      humoral and cellular immune system with the structural components in the
      peripheral nervous system may determine the extent of inflammation and possibly
      repair mechanisms. The animal model experimental autoimmune neuritis (EAN) allows
      detailed study of the various effector pathways and tests novel therapeutic
      strategies in vivo. Unexpectedly, involvement of the immune system is also found
      in animal models for inherited neuropathies and in its human counterpart Charcot
      Marie-Tooth (CMT) disease, suggesting an autoimmune reaction triggered by the
      genetically determined demyelinating disorder. A better understanding of immune
      regulation and its failure in the peripheral nervous system may help to develop
      more specific and more effective immunotherapies.

PMID- 12062259
TI  - Charcot-Marie-Tooth disease type 2C: a distinct genetic entity. Clinical and
      molecular characterization of the first European family.
AB  - Charcot- Marie-Tooth disease type 2 is clinically and genetically heterogeneous.
      A particular clinical subtype of autosomal dominant Charcot-Marie-Tooth disease
      type 2, characterized by diaphragm and vocal cord paralysis, is labelled Charcot
      Marie-Tooth disease type 2C but no genetic locus has been mapped for this form.
      We describe the first European family affected by Charcot-Marie-Tooth disease
      type 2C. Genetic analysis excluded linkage to locus of Charcot-Marie-Tooth
      disease type 2A, B, D, E and F, and to locus of distal hereditary motor
      neuronopathy type VII. In this family the disease has high penetrance, variable
      severity and apparently the most severe limb muscle involvement in the youngest
      generation. Vocal cord paralysis is unrelated to the degree of muscular weakness
      and patients with the most severe muscle involvement have absent or minimal
      respiratory symptoms. Charcot-Marie-Tooth disease type 2C is clinically and
      genetically different from Charcot-Marie-Tooth disease type 2A, B, D, E and F,
      and is not allelic with distal hereditary motor neuronopathy type VII.

PMID- 12062261
TI  - 76th ENMC International Workshop: pathophysiology and therapy in the mdx mouse 21
      23 January 2000, Naarden, The Netherlands.

PMID- 12062262
TI  - Special Centennial Workshop-- 101st ENMC International Workshop: Therapeutic
      Possibilities in Duchenne Muscular Dystrophy, 30th November-2nd December 2001,
      Naarden, The Netherlands.

PMID- 12062263
TI  - Surgical management of aortopulmonary window: a 40-year experience.
AB  - OBJECTIVES: An aortopulmonary window (APW) is a communication between the
      pulmonary artery (PA) and the ascending aorta in the presence of two separate
      semilunar valves. The purpose of this review is to describe the evolution of
      surgical techniques and results of surgical correction of APW at a single center
      over a 40-year time period. METHODS: Between 1961 and 2001, 22 patients underwent
      repair of APW. Age ranged from 11 days to 13 years (median 0.3 years). Associated
      cardiac lesions included interrupted aortic arch (IAA) (four), right PA origin
      from the aorta (four), ventricular septal defect (three), atrial septal defect
      (one), tetralogy of Fallot (one), and transposition of the great arteries (one).
      Mean preoperative pulmonary vascular resistance was 5.4 U/m2 (n=17). Two patients
      had attempted ligation without cardiopulmonary bypass (CPB), one patient had
      division and oversewing of the APW between clamps on CPB. Ten patients had the
      APW divided on CPB with primary aortic closure. Three patients had circulatory
      arrest for APW division, IAA repair, and anastomosis right PA to main PA. Most
      recently, six patients have had open transaortic patch closure (one of these had
      simultaneous arterial switch, one had simultaneous IAA repair). Follow-up in
      operative survivors ranges from 1 month to 26 years (median 8 years). RESULTS:
      There were five early deaths and one late death (pulmonary hypertension) in the
      first 16 patients where the primary strategy was APW division (37% mortality).
      There have been no deaths in the most recent six patients having transaortic
      patch closure. The patients with transaortic patch closure at a maximum of 8
      years follow-up are demonstrating normal PA and aortic growth. CONCLUSIONS: Early
      correction of APW with a transaortic patch and repair of all other associated
      cardiac anomalies at the time of diagnosis is advised.

PMID- 12062264
TI  - Atrial cardiomyoplasty in a Fontan circulation.
AB  - INTRODUCTION: The Fontan circulation is a direct connection between the systemic
      veins and the pulmonary artery (PA). Consequently, the pulmonary flow is passive
      due to the gradient between the right and left atrial pressure. In patients with
      increased pulmonary vascular resistance, the surgical procedure of atrio
      pulmonary connection is therefore prone to failure. The goal of this experiment
      was to increase the pulmonary flow in an experimental model of a Fontan
      circulation by performing a right atrial cardiomyoplasty (ACMP). METHODS: In 19
      Foxhounds the left m. latissimus dorsi (LD) was mobilised and transferred as a
      pedicle into the chest. After sternotomy a 'Fontan circulation' was created under
      cardiopulmonary bypass (CPB) by connecting the right atrium (RA) with the PA by a
      valveless conduit. The tricuspid valve was closed with a patch. In 11 dogs (group
      1) a valve was implanted in the inferior vena cava (IVC) and pulmonary inflow
      impedance was increased by partial occlusion of the conduit to a gradient of 10
      mmHg between RA and PA. In the other eight dogs (group 2) no valve was implanted,
      but flowmeters were placed in the IVC and the superior vena cava (SVC). In all
      dogs the RA was enlarged by a fascia lata patch before the LD was wrapped over
      the RA and stimulated synchronously to the R-wave with burst impulses. RESULTS:
      After coming off CPB, relatively high central venous pressures (22.5+/-5.8 mmHg)
      were necessary to maintain haemodynamic stability. With LD-stimulation in a 1:3
      mode in group 1, RA pressure (P) increased from 23.1+/-7.7 to 45+/-10.5 mmHg
      (P<0.001), pulmonary atrial pressure (PAP) from 15.5+/-4.3 to 25.5+/-7.6 mmHg
      (P<0.001) and central venous pressure increased to 33.1+/-11.3 mmHg (P<0.05).
      Stroke volume increase from 11.4+/-4.7 to 17.2+/-4.3 ml and peak conduit-flow
      from 1286.3+/-880.3 to 2329+/-1173 ml/min (all P<0.001). In a 1:1 stimulation
      mode a pulsatile pressure/flow profile was obtained in the PA-conduit.
      Furthermore, at higher frequencies of about 120 beats/min muscle relaxation was
      still fast enough as not to interfere with the RA filling. In group 2 caval flow
      without stimulation occurred mainly during diastole. However, with LD
      stimulation, a strong backflow into IVC and SVC was observed resulting in a less
      pronounced pressure/flow increase in the PA. CONCLUSIONS: Our experimental model
      demonstrates the possibility of a 'ventricularisation' of the RA by using the
      force of the LD. However, the haemodynamic benefit of ACMP was achieved only,
      when a valve was implanted in the ICV.

PMID- 12062266
TI  - The results of radial artery Y-graft for complete arterial revascularization.
AB  - OBJECTIVE: Harvesting of multiple arterial grafts is commonly associated with
      prolonged operating times and increased trauma in complete arterial coronary
      artery bypass grafting (CABG). Using sequential grafting techniques, CABG is
      possible with only two arterial grafts in multi-vessel coronary artery disease
      (CAD). However, sequential grafting may not be convenient for all circumstances
      and sometimes surgical technique may be challenging. We present our experience in
      the use of radial artery (RA) Y-graft on a routine basis. METHODS: Between
      January 1996 and November 2001, 127 patients (aged 63+/-8 years) with the
      diagnosis of multi-vessel disease underwent complete arterial revascularization
      using left internal mammarian artery (LIMA) and RA. Left ventricular ejection
      fraction ranged from 23 to 65% (mean 51+/-11%). Triple-vessel disease was present
      in 73.2% of patients. We used the division technique of RA during harvesting and
      formation of one or more composite Y-grafts of the RA itself to allow end-side
      rather than sequential anastomoses without any significant decrease the usable
      conduit length. The results of this technique were compared with the data of
      patients (n=109) who underwent completely arterial CABG with the use of the
      multiple arterial grafts in the same period. RESULTS: LIMA was anastomosed to the
      left anterior descending coronary artery (LAD) system in all patients. Two to
      four (mean 2.8+/-0.6) anastomoses were performed with RA Y-graft per patient.
      Proximal end of the radial graft was anastomosed to LIMA (60.6%) or aorta
      (39.4%). Mean operating time was 185 (45 min; bypass time, 68+/-23 min; and cross
      clamp time, 49+/-17 min). Perioperative intraaortic balloon pump was necessary in
      five patients (3.9%). There was no operative mortality or morbidity. During the
      follow-up period of 2-30 months, none of the patients had any complication.
      Postoperative coronary angiography in 54 patients (42.5%) documented excellent
      early patency rates (LIMA 100%, and RA 98.1%). CONCLUSIONS: We believe that
      keeping our technique in their armamentarium will be useful for cardiac surgeons
      as an alternative method during complete arterial revascularization. This
      approach allows for complete arterial revascularization in multi-vessel CAD using
      only single IMA and RA grafts with excellent early results.

PMID- 12062265
TI  - Delayed sternal closure: a life-saving measure in neonatal open heart surgery;
      could it be predictable?
AB  - OBJECTIVES: The tight syndrome after open-heart procedures in neonates renders
      delayed sternal closure (DSC) a life-saving measure. The goal of this study is to
      analyze the risk factors that may predict the need for DSC. METHODS: Between
      January 1991 and December 2000, 312 consecutive open-heart procedures in neonates
      (180 males, 132 females) were studied retrospectively. Median age was 11.9 days
      (range 1-30 days) and weight 3.63 kg (range 1.8-4.2 kg). The major pathologies
      were transposition of the great arteries (153), interruption of the aortic arch
      (IAA) (33), total anomalous pulmonary venous drainage (TAPVD) (24) and single
      ventricle (19). Two hundred and twenty-eight patients had profound hypothermia
      with circulatory arrest and 74 normothermic cardiopulmonary bypass (CPB), 195 had
      crystalloid cardioplegia and 111 blood cardioplegia. Median CBP time was 146 min
      (range 37-284 min) and aortic clamping 67.6 min (range 0-164 min). Two hundred
      and fifty-five patients had a continuous ultrafiltration and 57 had a modified
      ultrafiltration. The criteria for DSC were hemodynamic instability, deterioration
      of the central venous saturation, metabolic status and/or high ventilatory
      pressures. RESULTS: One hundred and nineteen patients had DSC (38.12%). Median
      CBP time was 145 min (range 37-284 min) and aortic clamping time 67.6 min (range
      0-164 min). Twenty-one patients (6.7%) needed reopening in the intensive care
      unit (ICU) during the first 24 h. Among the studied factors, the age below 7 days
      (P=0.014), the diagnosis of IAA and TAPVD (P<0.05), CBP duration over 185 min
      (P=0.048), clamping time over 98 min (P=0.039) and central venous saturation
      below 51% P=0.024) were statistically significant risk factors. All the patients
      who had more than 106 min of clamping, more than 196 min of cardiopulmonary
      bypass or less than 47% of central venous saturation were either left opened or
      reopened in the ICU. CONCLUSIONS: Many of the factors thought to be associated
      with the need for delaying the sternal closure had no statistical significance as
      risk factors. On the other hand, the diagnosis of IAA or TAPVD, an age less than
      7 days, aortic clamping more than 98 min, CPB time more than 185 min and a post
      bypass central venous saturation less than 51% were statistically significant
      risk factors that could be used in predicting the need for delaying the sternal
      closure.

PMID- 12062268
TI  - Systematic review of beating heart surgery with the Octopus Tissue Stabilizer.
AB  - The safety and efficacy of off-pump coronary artery bypass surgery with the aid
      of the Octopus Tissue Stabilizer (Octopus OPCAB), in comparison to conventional
      on-pump coronary artery bypass surgery (CPB-CABG), was examined by a systematic
      assessment of the peer-reviewed literature. The limited comparative data
      suggested that there was no difference in safety outcomes between Octopus OPCAB
      and CPB-CABG. The paucity of efficacy data reported in the higher level
      comparative studies meant that it was impossible to assess whether Octopus OPCAB
      was more efficacious than CPB-CABG. The evidence base for the procedure was
      deemed inadequate and an audit of the procedure was recommended.

PMID- 12062267
TI  - Angiographic evaluation of the luminal changes in the radial artery graft in
      coronary artery bypass surgery: a concern over the long-term patency.
AB  - OBJECTIVE: The radial artery graft (RA) still involves two unsolved problems,
      namely, vasospasm and intimal hyperplasia, although satisfactory early and mid
      term outcomes have been obtained recently. METHODS: Two hundred patients
      underwent coronary artery bypass surgery with RA between October,1996 and
      December,2000. We made a comparison of the luminal diameters at early and mid
      term periods in 23 patients who underwent mid-term angiographies after a mean
      follow-up of 27 months. The proximal anastomoses of the RA were the ascending
      aorta in these patients. The G/N ratio was determined as a ratio of the luminal
      diameter of the graft to that of the revascularized coronary artery so as to
      evaluate the luminal discrepancy between the graft and the native artery.
      RESULTS: In the 122 patients who underwent angiographies about one month after
      the operation, the patency rate was 99% (144 of 145) in the RA, 97% (139 of 143)
      in the left internal thoracic artery graft (LITA), 96% (75 of 78) in the
      saphenous vein graft (SV). In the 23 patients who underwent mid-term
      angiographies, the patency rate was 91% (24 of 26) in the RA, 100% (23 of 23) in
      the LITA, and 83% (20 of 24) in the SV. The luminal diameters of the RA and LITA
      significantly increased from 2.15 to 2.52 mm, and from 1.75 to 1.97 mm,
      respectively. The luminal change from 3.78 to 3.33 mm in the SV was not
      significant. The G/N ratios changed from 1.10 to 1.31, from 1.01 to 1.13, and
      from 2.05 to 1.86 in the RA, LITA, and SV, respectively. The change of the RA
      alone was statistically significant. CONCLUSIONS: The angiographic early patency
      rate was almost the same in three kinds of graft material, but the mid-term
      patency rate of the RA was between those of the LITA and SV. The mid-term luminal
      dilatation of the RA could involve two conflicting characteristics, namely, a
      good intimal function and a propensity to increase in the luminal discrepancy.
      Therefore, a further observation is required to evaluate whether the clinical
      outcome of the RA could remain as good as that of the LITA in the long-term
      period.

PMID- 12062269
TI  - Results of surgery for irreversible moderate to severe mitral valve regurgitation
      secondary to myocardial infarction.
AB  - OBJECTIVE: Moderate to severe irreversible mitral regurgitation secondary to
      myocardial infarction is an independent risk factor for reduced long-term
      survival. Late effects of correction of mitral incompetence concomitant with
      coronary artery bypass grafting (CABG) are less well known and the choice of
      mitral valve procedure is still debated. METHODS: From 1988 to 1998, 93
      consecutive patients (mean age 63+/-9 years) were treated for moderate to severe
      irreversible mitral regurgitation secondary to myocardial infarction; 84 were in
      NYHA functional class III-IV and 19 were in cardiogenic shock. Thirty-seven
      patients underwent emergency surgery. Perioperative intraaortic balloon pump
      (IABP) was necessary in 33 patients. Follow-up ranged from 6 months to 12 years
      (mean 51 months+/-41). RESULTS: Mitral valve was repaired in 30 patients and
      replaced in 63. Replacement was preferably performed in patients with major
      displacement of papillary muscle and in patients with acute papillary muscle
      rupture. CABG (3.4 distal anastomoses) was performed in all patients and was
      complete in 92%. Early mortality was 15% (14/93). Multivariable analysis
      identified need for IABP (P=0.005) and COPD (P=0.02) as risk factors for early
      death. Emergency surgery had only a trend (P=0.15) for increased mortality; age,
      low ejection fraction, repair vs. replacement had no influence. Actuarial
      survival rates at 1, 5 and 10 years were 81, 65 and 56%, respectively. Late
      survival was similar in patients with replacement or repair (P=0.46). At last
      follow-up, all but one patient were in NYHA functional class I or II.
      CONCLUSIONS: Combined mitral valve procedure and myocardial revascularization, as
      complete as possible, for moderate to severe mitral regurgitation secondary to
      myocardial infarction achieve satisfactory early and late outcome despite the
      increased operative mortality. Acute papillary muscle rupture, severe restriction
      of the mitral valve by major displacement of the papillary muscle are better
      managed by valve replacement.

PMID- 12062270
TI  - Postoperative mediastinitis in cardiac surgery - microbiology and pathogenesis.
AB  - OBJECTIVE: During 1992-2000, postoperative mediastinitis developed after 126
      (1.32%) of 9557 consecutive cardiac surgery procedures. The study was done to
      describe the variation in clinical characteristics and microbiological etiology
      in mediastinitis. METHODS: The records of 126 cases of postoperative
      mediastinitis were reviewed. RESULTS: The median time from operation to the
      development of mediastinitis was 7 days. Sternal dehiscence was seen in 86
      patients (68%). Coagulase negative staphylococci (CNS) were isolated in 46% of
      the cases with a verified microbiological etiology, Staphylococcus aureus in 26%
      and gram-negative bacteria in 18%. CNS were more frequently isolated in patients
      with sternal dehiscence (44/80, 55%) than in patients with stable sternum (10/38,
      26%) (P=0.003). However, S. aureus was more frequent in patients with stable
      sternum (18/38, 47%) than in patients with sternal dehiscence (13/80, 16%)
      (P<0.001). High body mass index was associated with coagulase negative
      staphylococci (P<0.001) and with sternal dehiscence (P=0.008). Chronic
      obstructive pulmonary disease was also associated with sternal dehiscence
      (P<0.001) and with coagulase negative staphylococci (P=0.04). Patients who had
      been reoperated before onset of mediastinitis tended to have an increased risk
      for a gram-negative etiology (32 vs. 15% in patients not reoperated, P=0.06). The
      overall 90-day all cause mortality in patients with mediastinitis was 19%. High
      age, need for reoperation before mediastinitis, and a long primary operation time
      was associated with increased mortality (P=0.02, P=0.007 and P=0.001,
      respectively). No specific bacterial etiology was associated with increased
      mortality nor was the presence of bacteriemia. CONCLUSIONS: Three different types
      of postoperative mediastinitis can be distinguished: (1) mediastinitis associated
      with obesity, chronic obstructive pulmonary disease, and sternal dehiscence,
      typically caused by coagulase negative staphylococci; (2) mediastinitis following
      peroperative contamination of the mediastinal space, often caused by S. aureus,
      and (3) mediastinitis mainly caused by spread from concomitant infections in
      other sites during the postoperative period, often caused by gram negative rods.
      The proposed classification of mediastinitis into three groups with different
      pathogenic mechanisms may be useful in understanding which prophylactic counter
      measures have the potentials to be effective in a given situation.

PMID- 12062271
TI  - Disruption and infection of median sternotomy: a comprehensive review.
AB  - Disruption and infection of median sternotomy wounds are grave complications
      often associated with prolonged hospitalization, high cost, and significant
      mortality. Effective prevention techniques are still debated. Successful
      management requires early recognition based on a high index of suspicion,
      detailed physical examination, appreciation of the clinical signs and symptoms,
      timely imaging studies, and prompt surgical therapy. Improvements in
      perioperative management and critical care of patients with multisystem organ
      failure can reduce morbidity and mortality rates. Sternal salvage and direct
      sternal reclosure are possible when the infection is diagnosed early. Techniques
      utilizing lateral sternal support should be first-line options in the condition.
      Muscle flap techniques should be the next consideration when direct closure has
      failed or cannot be attempted.

PMID- 12062272
TI  - A new concept of integrated cardiopulmonary bypass circuit.
AB  - OBJECTIVE: Standard cardiopulmonary bypass (CPB) circuits with their large
      surface area and volume contribute to postoperative systemic inflammatory
      reaction and hemodilution. In order to minimize these problems a new approach has
      been developed resulting in a single disposable, compact arterio-venous loop,
      which has integral kinetic-assist pumping, oxygenating, air removal, and gross
      filtration capabilities (CardioVention Inc., Santa Clara, CA, USA). The impact of
      this system on gas exchange capacity, blood elements and hemolysis is compared to
      that of a conventional circuit in a model of prolonged perfusion. METHODS: Twelve
      calves (mean body weight: 72.2+/-3.7 kg) were placed on cardiopulmonary bypass
      for 6 h with a flow of 5 l/min, and randomly assigned to the CardioVention system
      (n=6) or a standard CPB circuit (n=6). A standard battery of blood samples was
      taken before bypass and throughout bypass. Analysis of variance was used for
      comparison. RESULTS: The hematocrit remained stable throughout the experiment in
      the CardioVention group, whereas it dropped in the standard group in the early
      phase of perfusion. When normalized for prebypass values, both profiles differed
      significantly (P<0.01). Both O2 and CO2 transfers were significantly improved in
      the CardioVention group (P=0.04 and P<0.001, respectively). There was a slightly
      higher pressure drop in the CardioVention group but no single value exceeded 112
      mmHg. No hemolysis could be detected in either group with all free plasma Hb
      values below 15 mg/l. Thrombocyte count, when corrected by hematocrit and
      normalized by prebypass values, exhibited an increased drop in the standard group
      (P=0.03). CONCLUSION: The CardioVention system with its concept of limited
      priming volume and exposed foreign surface area, improves gas exchange probably
      because of the absence of detectable hemodilution, and appears to limit the
      decrease in the thrombocyte count which may be ascribed to the reduced surface.
      Despite the volume and surface constraints, no hemolysis could be detected
      throughout the 6 h full-flow perfusion period.

PMID- 12062273
TI  - Adenoviral gene transfer to the heart during cardiopulmonary bypass: effect of
      myocardial protection technique on transgene expression.
AB  - OBJECTIVE: Adenoviral gene transfer to the arrested heart during cardiopulmonary
      bypass (CPB) is a novel method of allowing prolonged vector contact with the
      myocardium. In this model we investigated the importance of temperature, duration
      of arrest and cardioplegia on transgene expression. METHODS: First-generation
      adenoviral vector (1 x 10(12) total viral particles) containing the transgene for
      the human beta2-adrenoceptor (Adeno-beta(2)AR) or beta-galactosidase (Adeno
      beta(gal)) was delivered to neonatal piglets via the proximal aorta, during
      simulated cardiac surgery, and allowed to dwell for the cross-clamp duration.
      Four treatment groups received Adeno-beta(2)AR. Groups A (n=4) and B (n=6)
      underwent cold crystalloid cardioplegia arrest for 10 and 30 min, respectively,
      Group C (n=5) underwent warm crystalloid cardioplegia arrest for 10 min, and
      Group D (n=5) underwent warm fibrillatory arrest for 10 min. Group E (n=6)
      received Adeno-beta(gal) and underwent cold crystalloid cardioplegia arrest (30
      min). Animals were weaned off CPB and recovered for 2 days. Receptor density was
      assessed in membrane fractions using radioligand binding and compared using the
      Mann-Whitney U-test. RESULTS: Left ventricular transgene overexpression, as
      evidenced by elevated betaAR density, following Adeno-beta(2)AR treatment was
      greatest with cold cardioplegia (Group A 588+/-288.8 fmol/mg; P=0.002 and Group B
      520+/-250.9 fmol/mg; P=0.01) versus control (Group E 109+/-8.4 fmol/mg).
      Overexpression also occurred with warm cardioplegia (Group C 274+/-69.5 fmol/mg;
      P=0.05) and ventricular fibrillation (Group D 215+/-48.4 fmol/mg; P=0.02) versus
      control. Comparison of the combined cold cardioplegia groups versus those treated
      with warm conditions showed a trend towards increased expression with cold
      conditions (P=0.1). Receptor density was also significantly increased in the
      right ventricle of animals in Group B (165+/-18.1 fmol/mg; P=0.03) and Group D
      (181+/-23.4 fmol/mg; P=0.02) versus control (Group E 118+/-5.8 fmol/mg).
      CONCLUSIONS: Cold crystalloid cardioplegia is not detrimental to gene transfer in
      vivo. In fact, there was a trend towards increased left ventricular transgene
      expression when the adenoviral vector was delivered following cold versus warm
      cardioplegia. Shorter periods of contact with the vector may reduce transgene
      overexpression. Therefore, gene transfer is possible during cardiac surgery with
      clinically used myocardial protection techniques.

PMID- 12062274
TI  - Transplanted fetal cardiomyocytes as cardiac pacemaker.
AB  - BACKGROUND: While morphologic integration of transplanted fetal cardiomyocytes
      into the ventricular myocardium is a well-known fact, no studies have yet shown
      transplanted cells to coherently contribute to contraction and electrical
      excitation of the host myocardium. The aim of this study was to prove the
      hypothesis that by transplanting cardiomyocytes with a higher intrinsic rhythmic
      rate into the myocardium of the left ventricle, these cells could act as an
      ectopic pacemaker by functional coupling with host cardiomyocytes. METHODS AND
      RESULTS: Dissociated fetal canine atrial cardiomyocytes including sinus nodal
      cells were delivered into the free wall of the left ventricle of adult canine X
      linked muscular dystrophy dogs (n=2). These dogs fail to express Dystrophin in
      both cardiac and skeletal muscle. In the control group (n=2) fetal skin
      fibroblasts were used for grafting. A total of 3-4 weeks after transplantation
      the dogs underwent catheter ablation of the atrioventricular node (AV-node) and
      subsequent electrophysiological mapping studies. Transplanted cells were
      identified by Dystrophin immunoreactivity, indicating survival and morphological
      integration in the recipient heart. The expression of Connexin 43 between donor
      and recipient cells suggested formation of gap junctions between injected and
      host cardiomyocytes. After catheter ablation of the AV-node, a ventricular escape
      rhythm emerged driving the pace of the heart and originating from the labeled
      transplantation site. This effect could not be observed in the control group
      (n=2). CONCLUSIONS: The results constitute the first observation of phenomena
      indicating electrical and mechanical coupling between allogeneic donor
      cardiomyocytes and recipient myocardium in-vivo. Further experiments are
      necessary to evaluate the technique as a potential therapy for atrioventricular
      block.

PMID- 12062275
TI  - Bilateral lung transplantation with intra- and postoperatively prolonged ECMO
      support in patients with pulmonary hypertension.
AB  - OBJECTIVE: Lung transplantation for pulmonary hypertension (PH) is usually
      performed on cardiopulmonary bypass, with the disadvantage of full systemic
      anticoagulation, uncontrolled allograft reperfusion and aggressive ventilation.
      These factors can be avoided with intra- and postoperatively prolonged
      extracorporeal membrane oxygenator (ECMO) support. PATIENTS AND METHODS: Between
      February 1999 and March 2001, 17 consecutive patients with PH (systolic pulmonary
      artery pressure >70 mmHg) of different etiologies underwent bilateral lung
      transplantation (BLTX). There were 11 females and six males in the age range from
      7 to 50 years (mean age, 28.4+/-12.9 years). Six patients were preoperatively
      hospitalized, four in the intensive care unit (ICU), one was on ECMO for 3 weeks
      pretransplantation, and one was resuscitated and bridged with ECMO for 1 week
      until transplantation. Femoral venoarterial ECMO support with heparin-coated
      circuits was set up after induction of anesthesia and discontinued at the end of
      surgery (n=3) or extended for 12 h median into the postoperative period (n=14).
      Postoperative ventilation pressure was kept below 25 mmHg. Allograft function at
      2 h after discontinuation of ECMO, outcome and adverse events were monitored in
      all patients. Mean follow up time was 18+/-11.4 months. RESULTS: The
      perioperative mortality was 5.9% (n=1). Arterial oxygen pressure measured 2 h
      after weaning from ECMO, and under standard mechanical ventilation with a peak
      pressure of 25 mmHg and inspired oxygen fraction of 0.4, was 157+/-28 mmHg. The
      mean pulmonary artery pressures were reduced to 29+/-3,4 from 66+/-15 mmHg before
      transplantation. Postoperative complications included rethoracotomy due to
      bleeding (n=4) and temporary left ventricular failure (n=4). Median ICU stay was
      12 days. Incidence of rejection within the first 100 days was 0.4 per patient.
      CONCLUSION: BLTX with intraoperative and postoperatively prolonged ECMO support
      provides excellent initial organ function due to optimal controlled reperfusion
      and non-aggressive ventilation. This results in improved outcome even in advanced
      forms of PH.

PMID- 12062276
TI  - Early experience with robotic technology for thoracoscopic surgery.
AB  - OBJECTIVE: Recently, robots have been introduced into surgical procedures in an
      attempt to facilitate surgical performance. The purpose of this study was to
      develop a technique to perform thoracoscopic lung resection using a
      telemanipulation system. METHODS: We have used a robotic system to perform
      thoracoscopic surgery in 12 cases: five lobectomies, three tumor enucleations,
      three excisions and one bulla stitching completed with fibrin glue for
      spontaneous pneumothorax. The operations were performed using the Intuitive
      Microsurgical system (Da Vinci System) through three ports and, a fourth space
      'service entrance' incision, in the major lung resection. RESULTS: Three
      procedures begun with the robotic technique were completed by a minimal
      thoracotomy. No technical operative mishaps were associated with the manoeuvres
      of robotic arms. In all manoeuvres (up, down, insertion, extraction, etc.), the
      robotic arms moved appropriately in the favorable operative fields. All patients
      tolerated the procedure well and the post-operative course was satisfactory,
      requiring few analgesics. CONCLUSIONS: Although further studies on robotically
      assisted procedures are needed to clarify the clinical feasibility of this
      procedure, the results in our cases are encouraging. We believe that
      thoracoscopic procedures using a robotic manipulation system may be technically
      feasible in selected cases and in the hands of experienced thoracic surgeons.

PMID- 12062277
TI  - Minimally invasive endoscopic repair of pectus excavatum.
AB  - OBJECTIVE: We report our initial 3 years 4 months' single institution experience
      in 31 consecutive patients with pectus excavatum treated with minimally invasive
      endoscopic pectus excavatum repair utilizing a modification of the 'Nuss'
      technique. METHODS: Under general anesthesia, a curved steel bar is individually
      shaped for each patient to match the ideal chest wall shape and is placed through
      an endoscopically created retrosternal tunnel between two bilateral midaxillary
      line 2-cm incisions. The tunnels initially go along the outside of the rib cage,
      under the pectoral muscles. At the level of the sternum, these tunnels go
      retrosternal and communicate with each other. The steel bar is passed with the
      convexity facing posteriorly, within a protective flat silastic drain. Under
      endoscopic guidance, the curved steel bar is passed through one tunnel, under the
      sternum, and out the other tunnel. Once positioned, the bar is turned over,
      thereby correcting the deformity. An epidural catheter provides perioperative
      pain relief. RESULTS: Minimally invasive endoscopic pectus excavatum repair has
      been performed on 31 patients (age: range 4.4-31.0 years, median 15.0 years, mean
      14.5 years). Median hospital length of stay is 4 days (range 3-10 days, mean 4.6
      days). Pneumothorax occurred in five patients requiring tube thoracostomy in
      three. One patient developed delayed bilateral pleural effusions requiring
      drainage. Two patients developed evidence of sterile seroma formation at the skin
      incision several months after minimally invasive repair of pectus excavatum.
      These seromas resolved with non-interventional conservative medical treatment. No
      other complications occurred. CONCLUSION: The minimally invasive endoscopic
      pectus repair is safe and effective and currently our procedure of choice for
      primary pectus excavatum in all ages. Endoscopic visualization facilitates the
      safe creation of the retrosternal tunnel. Short-term results have been excellent.
      Further follow-up will be necessary to determine long-term results.

PMID- 12062278
TI  - Thoracic wall reconstruction using both portions of the latissimus dorsi
      previously divided in the course of posterolateral thoracotomy.
AB  - OBJECTIVE: Besides other factors, the choice of reconstructive method for full
      thickness thoracic wall defects depends on the morbidity of preceding surgical
      procedures. The pedicled latissimus dorsi flap is a reliable and safe option for
      reconstruction of the thorax. A posterolateral thoracotomy, however, results in
      division of the muscle. Both parts of the muscle can be employed to close full
      thickness defects of the chest wall. The proximal part can be pedicled on the
      thoracodorsal vessels or the serratus branch; the distal part can be pedicled on
      paravertebral or intercostal perforators. This retrospective study was undertaken
      to evaluate the reconstructive potential of both parts of the latissimus dorsi in
      thoracic wall reconstruction after posterolateral thoracotomy. METHODS: Between
      1987 and 1999, 36 consecutive patients underwent reconstruction of full-thickness
      thoracic wall defects with latissimus dorsi-flaps after posterolateral
      thoracotomies. The defects resulted from infection and open window thoracostomy
      (n=31), trauma (n=3) and resection of tumours (n=2). The patients' average age
      was 57 years (range 22-76 years). Twenty-five patients were male, 11 were female.
      In 31 cases the split latissimus dorsi alone was employed; in five cases
      additional flaps had to be used due to the size of the defects, additional
      intrathoracic problems or neighbouring defects. RESULTS: In 34 cases defect
      closure could be achieved without major complications. Empyema recurred in the
      pleural cavity in one case and one patient died of septicaemia. The 15 patients
      who had required a respirator in the preoperative phase could be extubated 4.8
      days (average) after thoracic wall reconstruction. Postoperative hospital stay
      averaged 16 days. CONCLUSIONS: Different methods are available for reconstruction
      of full thickness defects of the thoracic wall. After posterolateral thoracotomy
      in the surgical treatment of empyema, oncologic surgery and traumatology, the
      latissimus dorsi muscle still retains some reconstructive potential. Advantages
      are low additional donor site morbidity and anatomical reliability. As it is
      located near the site of the defect, there is no need for additional surgical
      sites or intraoperative repositioning. In our service, the split latissimus dorsi
      muscle flap has proven to be a valuable and reliable option in thoracic wall
      reconstruction.

PMID- 12062279
TI  - Mechanical vascular division in lung resection.
AB  - BACKGROUND: There is little information available regarding the relative
      advantage of stapling over ligation for major pulmonary vessels in lung
      resection. The thin and fragile structure of pulmonary vascular walls for their
      large luminal size might have made surgeons reluctant to use staplers. This study
      was intended to demonstrate the feasibility of pulmonary vascular division by
      staplers. METHODS: A total of 842 mechanical vascular divisions were performed
      for pulmonary artery (PA, n=376), pulmonary vein (PV, n=462), and azygos vein
      (AV, n=4) in 603 consecutive pulmonary resections from 1997 to 1999 at the
      National Cancer Center Hospital, Tokyo. In this series, 99.8% of mechanical
      vascular divisions were performed with endostaplers (840 vessels), and only 0.2%
      was performed with conventional TA-type staplers (two vessels). The prevalence of
      problems related to mechanical stapling (stapling failure) and postoperative
      bleeding was studied retrospectively. RESULTS: There was only one incidence of
      stapling failure, in which the superior pulmonary vein was divided without the
      formation of staples (overall stapling failure rate, 0.1%). The bleeding was
      controlled by ligation of each divided stump during thoracotomy. There was no
      stapling failure for PAs or AVs. In no case did postoperative bleeding require
      rethoracotomy at the stapled line of the vessels. CONCLUSIONS: Although temporary
      oozing was sometimes seen along the staple line, vascular division with
      endostaplers was highly reliable with only a 0.1% incidence of stapling failure
      for all kinds of vascular structures in the thorax.

PMID- 12062280
TI  - Surgery in bronchial carcinoids: experience with 83 patients.
AB  - OBJECTIVE: With the changing clinical presentation and histopathological pattern,
      carcinoids are now considered as a distinct and well-defined group in the
      neuroendocrine tumour scale. Surgery, especially parenchyma-sparing operations,
      are the treatment of choice for carcinoids. METHODS: Over a 25-year period, 83
      patients with typical carcinoid tumour underwent thoracotomy on in our
      institution. The records of the patients were reviewed and the results were
      evaluated. RESULTS: The diagnosis was made with radiological methods and
      bronchoscopy. Cough and recurrent pneumonia were the most common symptoms. A
      variety of surgical procedures were performed. Thirty of the 83 patients
      underwent tissue-saving operations. Twenty patients underwent bronchotomy
      excision, eight were managed with sleeve or partial sleeve resective procedures,
      and two underwent segmentectomy. CONCLUSIONS: Conservative surgery is the
      treatment of choice of carcinoids, which were histologically typical and
      anatomically endobronchial. Especially for polypoid type carcinoids and for
      selected cases with sessile type, bronchotomy with simple excision and sleeve
      resections is a simple and effective method. As these types of operations produce
      a better functional result, they should be encouraged in these patients.

PMID- 12062281
TI  - Sleeve lobectomy for non-small cell lung cancer and carcinoids: results in 160
      cases.
AB  - OBJECTIVE: To assess operative mortality (OM), morbidity and long-term results of
      sleeve lobectomies performed for non-small cell lung cancer (NSCLC) and
      carcinoids during a 35-year period. METHODS: A retrospective review of patients
      who underwent a sleeve lobectomy for NSCLC and carcinoids was undertaken,
      univariate and multivariate analyses of factors influencing early mortality in
      NSCLC were performed and for this purpose the series was split into an early and
      a contemporary phase, the Kaplan-Meier method was used to calculate the
      cumulative survival rate, and statistical significance was calculated with the
      log-rank test. Causes of death were evaluated in relation to the stage of the
      disease. RESULTS: OM for NSCLC was 14.6% in the early phase and 6% in the
      contemporary one; late stenosis occurred in 7.7% of NSCLC patients in the early
      phase and in 2% in the contemporary one. No OM or late stenosis occurred in
      carcinoid patients. Three, 5 and 10-year survival rates excluding carcinoids were
      77, 62 and 31% for stage I(A-B), 45, 34 and 27% for stage II(A-B), 33, 22 and 0%
      for stage III(A-B). The 10-year survival rate for carcinoids was 100%. There was
      no significant difference in long-term survival between stages II and III, while
      the difference between stage I and stages II and III was significant (P<0.001).
      When survival was analyzed in relation to nodal status, 3, 5 and 10-year survival
      rates were 71, 57 and 33% for N0 disease, 42, 33 and 22% for N1 disease, and 34
      and 19% with the last observation at 82 months of 19% for N2 disease; there was
      no significant difference in survival between N1 and N2 disease. A second primary
      lung cancer occurred in six patients (3.7%) who underwent resection. Late
      mortality was not related to cancer in most stage I patients while in stages II
      and III patients it was related to local and distant recurrences. CONCLUSIONS:
      Sleeve lobectomy is a valid alternative to pneumonectomy: careful patient
      selection and surgical technique make it possible to achieve a mortality rate
      comparable to or lower than that for pneumonectomy along with a better quality of
      life. In addition, it allows further lung resection, if necessary.

PMID- 12062282
TI  - A new method of segmental resection for primary lung cancer: intermediate
      results.
AB  - OBJECTIVE: To improve the postoperative results of limited resection for small
      lung cancer, we have developed a new operative method, pulmonary artery-guided
      segmentectomy. This resection begins with identification of the pulmonary
      arterial branches involved in the tumor, then the pulmonary tissue is divided
      along the pulmonary arteries (i.e. guided by pulmonary arteries) from the hilum
      toward the periphery by electrocautery. The advantages of this method include the
      facilitation of securing adequate margin from the tumor, and the feasibility of
      intralobar lymph node dissection during operation. To examine the efficacy of the
      new method of segmental resection, we retrospectively reviewed 74 cases of T1N0M0
      disease who underwent the pulmonary artery-guided segmentectomy. METHODS: From
      1993 to 2000, 74 patients with pathological T1N0M0 lung cancer were treated by
      the pulmonary artery-guided segmentectomy. Forty-one patients (55.4%) who
      underwent the segmentectomy had been considered suitable candidates for lobectomy
      (intentional resection group). The other 33 patients (44.6%) were considered poor
      candidates for lobectomy because of poor cardiopulmonary reserve (compromised
      resection group). RESULTS: The overall survival rate at 5 years was 82.0%. The 5
      year survivals in the intentional and the compromised resection groups were 81.6
      and 77.6%, respectively, and no significant differences were detected between the
      groups. According to tumor size, the 5-year survival rate for patients with
      tumors of 20 mm or smaller (92.9%, n=53) was higher than that for the patients
      with tumors of 21-30 mm (63.0%, n=21), but the difference did not reach
      statistical significance. Median follow-up time of 27.0 months revealed eight
      locoregional recurrences and four deaths due to lung cancer. Sixty-three patients
      (85.1%) are alive with no evidence of disease, and six patients (8.1%) are alive
      with recurrent disease. Locoregional recurrences occurred in one of 53 patients
      (1.9%) with tumors 20 mm or smaller and in seven of 21 patients (33.3%) with
      tumors 21-30 mm, the difference being statistically significant (P<0.01).
      CONCLUSIONS: Our intermediate results demonstrated that the new pulmonary artery
      guided segmentectomy could be an alternative method for selected patients with
      small lung cancer, particularly with tumors 20 mm or smaller in diameter.

PMID- 12062284
TI  - Is the reduction of forced expiratory lung volumes proportional to the lung
      parenchyma resection, 6 months after pneumonectomy?
AB  - OBJECTIVES: To preoperatively estimate the degree of first-second forced expired
      volume (FEV1) and forced vital capacity (FVC) reduction 6 months after
      pneumonectomy, according to the preoperative performed spirometry and
      bronchoscopy, and to estimate if the expected postoperative values of FEV1 and
      FVC are in accordance with the actual values. METHODS: Thirty-five patients, who
      underwent pneumonectomy for non-small cell lung cancer between 1996 and 1999,
      were included in the perspective study. All patients had total or near total
      bronchial obstruction at preoperative bronchoscopy. Patients were divided into
      three groups according to the preoperative bronchoscopy findings: Group I,
      obstruction of the main bronchus (six patients); Group II, obstruction of a lobar
      bronchus (19 patients); and Group III, obstruction of a segmental bronchus (10
      patients). The estimation of the percent reduction of FEV1 and FVC has been made
      according to the formula: percent reduction=(no. of bronchopulmonary segments to
      be resected-no. of obstructed segments) x 5.26%. RESULTS: The mean overall actual
      percent reduction of FEV1 and FVC differed significantly from the expected mean
      overall percent reduction of FEV1 and FVC (P=0.000 and P=0.001, respectively).
      The actual values were lower than the predicted values using the given formula.
      In group and subgroup analysis, the mean actual percent reduction of FEV1 and FVC
      differed significantly from the mean expected percent reduction of FEV1 and FVC
      in Groups I and II of patients (P<0.01), but no significant differences were
      observed in Group III of patients (P>0.05). No significant differences between
      expected and actual mean percent reduction of FEV1 and FVC was also observed in
      patients of Groups I and II, when lung or lobar atelectasis, respectively, was
      noted at preoperative chest X-ray (P>0.05). CONCLUSIONS: Only when a segmental
      bronchus was obstructed at the preoperative bronchoscopy or when lobar or lung
      atelectasis was the result of the main or lobar bronchus obstruction, the
      estimated, using the proposed formula, expected percent reduction of FEV1 and FVC
      values were close to the actual postoperative percent reduction of FEV1 and FVC.

PMID- 12062285
TI  - Pulmonary resection for metastases from colorectal cancer: factors influencing
      prognosis. Twenty-year experience.
AB  - OBJECTIVE: We reviewed our experience in the surgical management of 80 patients
      with colorectal pulmonary metastases and investigated factors affecting survival.
      MATERIAL AND METHODS: From January 1980 to December 2000, 80 patients, 43 women
      and 37 men with median age 63 years (range 38-79 years) underwent 98 open
      surgical procedure (96 muscle-sparing thoracotomy, one clamshell and one median
      sternotomy) for pulmonary metastases from colorectal cancer (three pneumonectomy,
      17 lobectomy, seven lobectomy plus wedge resection, six segmentectomy, three
      segmentectomy plus wedge resection and 62 wedge resection). Pulmonary metastases
      were identified at a median interval of 37.5 months (range 0-167) from primary
      colorectal resection. Second and third resections for recurrent metastases were
      done in seven and in four patients, respectively. RESULTS: Operative mortality
      rate was 2%. Overall, 5-year survival was 41.1%. Five-year survival was 43.6% for
      patients submitted to single metastasectomy and 34% for those submitted to
      multiple ones. Five-year survival was 55% for patients with disease-free interval
      (DFI) of 36 months or more, 38% for those with DFI of 0-11 months and 22.6% for
      those with DFI of 12-35 months (P=0.04). Five-year survival was 58.2% for
      patients with normal preoperative carcino-embryonic antigen (CEA) levels and 0%
      for those with pathologic ones (P=0.0001). Patients submitted to second-stage
      operation for recurrent local disease had 5-year survival rate of 50 vs. 41.1% of
      those submitted to single resection (P=0.326). CONCLUSIONS: Pulmonary resection
      for metastases from colorectal cancer may help survival in selected patients.
      Single metastasis, DFI>36 months, normal preoperative CEA levels are important
      prognostic factors. When feasible, re-operation is a safe procedure with
      satisfactory long-term results.

PMID- 12062287
TI  - Results of surgical treatment for pulmonary aspergilloma.
AB  - OBJECTIVES: The purpose of this retrospective study is to analyze the results of
      the surgical treatment for pulmonary aspergilloma and to confirm that aggressive
      surgical resection can provide effective outcome for these patients. PATIENTS AND
      METHOD: From 1987 to 2000, 110 patients underwent thoracotomy for treatment of
      pulmonary aspergilloma in two hospitals. The most common indication for operation
      was hemoptysis (82%). Underlying diseases were tuberculosis (89%), bronchiectasis
      (5%), carcinoma (3%), lung tumor (1%) and none (2%). The procedures were
      lobectomy (74%), segmentectomy (12%), wedge resection (9%), pneumonectomy (4%)
      and cavernoplasty in two patients. Twenty-nine patients (26%) had severe
      underlying intrathoracic pathologies. RESULTS: Postoperative complications
      occurred in 23.6% of the patients including: empyema (n=13), bleeding (n=6),
      respiratory insufficiency (n=2), wound infection (n=4) and bronchopleural fistula
      (n=1). There was one hospital death due to panperitonitis after gastric ulcer
      perforation. CONCLUSIONS: We recommend early surgical resection of symptomatic
      aspergilloma and even asymptomatic cases with reasonable complication.

PMID- 12062286
TI  - Long-term survival of atypical bronchial carcinoids with liver metastases,
      treated with octreotide.
AB  - OBJECTIVE: To demonstrate that liver metastases by radically resected atypical
      carcinoids of the lung can be effectively treated by new somatostatin analogs.
      METHODS: Between January 1977 and December 1999, 126 patients affected by
      bronchial carcinoids were submitted to a radical resection of the lung. Seven of
      them (5.5%) presented liver metastases 27, 22, 14, 18, 16, 12 and 9 months after
      surgery: carcinoid syndrome (CS) was ever present. 111In-DTPA-pentetreotide
      scintigraphy (Octreoscan) and ultrasound guided biopsy were performed in all
      cases, and the presence of somatostatin receptors sst2 was demonstrated by
      polymerase chain reaction (PCR) method. RESULTS: Five patients refused the
      proposed chemotherapy, and liver alcoholization was not feasible. Octreotide was
      administered at the dose of 1500 microg/daily subcutaneously. CS was controlled
      and also high urinary 5-hydroxyindoleacetic acid values returned to normal after
      a median of 7 days (range 4-10 days) of medical treatment. No important side
      effects were registered, and a good quality of life was observed. The patients
      are alive and well at 51, 36, 24, 24, 23, 19, and 16 months after the diagnosis
      of the metastases, respectively. In two cases ultrasounds revealed the reduction
      and in one case the complete resolution of the liver lesion. CONCLUSIONS:
      Octreotide is effective in controlling symptoms of CS of patients with liver
      metastases of resected atypical bronchial carcinoid. The efficacy of the drug is
      due to the presence of sst2 somatostatin receptors in the pathologic tissue, as
      demonstrated by PCR method. The positivity to Octreoscan depends on the presence
      of the same receptors. Octreoscan may be used in the follow-up of these
      neuroendocrine neoplasms of the lung. A positivity to Octreoscan is predictive
      for an effective therapy with octreotide.

PMID- 12062288
TI  - Endotracheal metastasis of rectal cancer.

PMID- 12062289
TI  - Large chest wall abscess due to microaerophilic streptococcus.

PMID- 12062290
TI  - Swordfish attack: an unusual cause of penetrating thoracic wound.

PMID- 12062291
TI  - Unsuspected vascular anomaly at cervical mediastinoscopy.

PMID- 12062292
TI  - Giant pulmonary artery aneurysm.

PMID- 12062293
TI  - Giant right coronary artery-coronary sinus fistula.

PMID- 12062294
TI  - Antegrade cerebral perfusion by axillary artery and left carotid artery inflow at
      moderate hypothermia.
AB  - Cerebral protection during hypothermic circulatory arrest was obtained by
      combining right carotid perfusion through the axillary artery with selective
      perfusion of the left common carotid artery in ten patients. We believe that the
      proposed technique offers several advantages. (1) The axillary artery is
      generally free from atherosclerosis. (2) It eliminates the risk of retrograde
      embolization. (3) It provides antegrade perfusion of the true lumen in aortic
      dissection. (4) Antegrade cerebral perfusion is never interrupted. (5)
      Bihemispheric perfusion is assured. (6) The risk of air embolysm during carotid
      cannulation is reduced.

PMID- 12062295
TI  - Video assisted resternotomy in high-risk redo operations - the St Mary's
      experience.
AB  - The incidence of re-operative median sternotomy is rising. During resternotomy,
      catastrophic haemorrhage remains a dreaded complication. We describe our approach
      and experience with the combined use of Mayfield resternotomy retractor and
      anterior sternal retraction which allows division of adhesions between the
      sternum and mediastinal structures under direct vision with endoscopic or
      conventional instruments prior to resternotomy with a standard Hall reciprocating
      saw. The mean time to divide the retro-sternal adhesions was 26.4+/-16.7 min. No
      morbidity related to sternal division was observed. For redo surgery, repeat
      sternotomy under direct vision may reduce the sternotomy related morbidity
      (especially the need for cardiopulmonany bypass due to significant haemorrhage)
      and mortality.

PMID- 12062296
TI  - Bronchogenic cyst infected by Salmonella enteritidis followed gastroenteritis.
AB  - Congenital bronchogenic cysts of the lung and mediastinum develop from the
      ventral foregut during embryogenesis. Bronchogenic cysts are seldom seen in the
      adults and most are thought to be asymptomatic and free of complications unless
      they become infected or are large enough to cause pressure on contiguous vital
      structures such as the tracheal carina, the lung or the esophagus. We present the
      unique case of a 24-year-old man who developed respiratory symptoms after
      Salmonella enteritidis infected bronchogenic cyst following Salmonella
      gastroenteritis.

PMID- 12062297
TI  - Lung scedosporiosis: a differential diagnosis of aspergillosis.
AB  - Lung scedosporiosis is an opportunistic fungus in humans that rarely affects the
      lung. It may give clinical presentations that are similar to aspergillosis.
      However, it must be detected because of its frequent resistance to medical
      treatment. Two cases of pulmonary scedosporiosis that were surgically treated are
      reported herein.

PMID- 12062298
TI  - Persistent cavitations in pulmonary mucormycosis after apparently successful
      amphotericin B.
AB  - A 67-year-old diabetic male developed bilateral pulmonary mucormycosis (PM).
      After long-term treatment with amphotericin B (cumulative dose of 30.6 g),
      clinical resolution was obtained, but small radiographic cavitations persisted. A
      late relapse occurred and bilateral lobectomy led to a definitive cure.
      Amphotericin B is not able to penetrate properly into PM cavitations. We suggest
      that persistence of cavitations should lead to consideration of surgery, even
      after a good response to amphotericin B.

PMID- 12062299
TI  - Primary leiomyosarcoma of the anterior mediastinum.
AB  - Primary mediastinal leiomyosarcoma are extremely rare tumors, which develop from
      smooth muscle, usually in the esophagus or main vessels. Very few cases have been
      reported in the literature and only two of these developed from small vessels in
      the soft tissue of the anterior mediastinum. We report on a 45-year-old man who
      presented with a huge anterior mediastinal tumor. The tumor was surgically
      removed with right thoracotomy and the diagnosis of well-differentiated
      leiomyosarcoma was established. It probably originated from the anterior
      mediastinal tissue, so at operation a continuity was not found between the tumor
      and neighboring structures. This rare and interesting histopathology is discussed
      and the literature is reviewed.

PMID- 12062300
TI  - Tracheal stenosis caused by false aneurysm of the right subclavian artery.
AB  - The development of tracheal stenosis following insertion of a central venous
      catheter is a rare complication of this procedure. We present the case of an 81
      year-old woman, who suffered acute onset of dyspnea, stridor and dysphagia 4
      weeks after coronary artery bypass surgery. Investigations revealed a false
      aneurysm of the right subclavian artery, compressing the trachea and the
      oesophagus. The iatrogenic lesion was caused by the insertion of a central venous
      catheter via the right subclavian route. By the time symptoms developed the
      catheter had already been removed.

PMID- 12062301
TI  - Endovascular treatment for intracranial mycotic aneurysms prior to cardiac
      surgery.
AB  - The management of patients with infective endocarditis complicated by
      intracranial mycotic aneurysms is controversial. We present the case of a 21-year
      old man who suffered from mitral regurgitation with small vegetations due to
      infective endocarditis. The problem was associated with a ruptured aneurysm on
      the right anterior cerebral artery and an unruptured aneurysm on the left middle
      cerebral artery. Endovascular embolization of these aneurysms and subsequent
      mitral valve repair led to a successful outcome.

PMID- 12062302
TI  - Preoperative risk factors for prolonged air leak following lobectomy or
      segmentectomy for primary lung cancer.

PMID- 12062303
TI  - Retrocaval right internal mammary artery for left ventricular marginal arteries
      grafting.

PMID- 12062305
TI  - Retrocaval route for the right internal mammary artery.

PMID- 12062307
TI  - Paradoxical effects of hedonic disparities in negative anticipatory contrast.
AB  - Negative anticipatory contrast (NAC) occurs when the presentation of two
      solutions in sequence over a number of trials leads to the suppression in
      consumption of the first solution. A hedonic 'disparity' between the two
      solutions may lead to this suppression. However, what the relative role of the
      gustatory properties versus the nutricaloric loads of the two solutions is in
      determining the acquisition of NAC is uncertain. Previous experiments have
      typically used saccharine and sucrose solutions, which resemble each other in
      gustatory properties yet differ in their nutricaloric loads. In contrast, the
      present experiments used soy milk and sucrose solutions, which are both highly
      nutritive but differ in their gustatory properties. Soy milk was found to have a
      higher hedonic value than a 16% sucrose solution as measured by both choice and
      absolute consumption. According to a hedonic disparity hypothesis, NAC should
      have occurred using a sucrose-soy sequence but not a soy-sucrose sequence.
      Paradoxically, the sucrose-soy sequence failed to yield NAC, but the soy-sucrose
      sequence did yield a repeatable, significant NAC. A consideration of the
      available theory and research indicated that NAC may be explained by a strong
      conditioning of a satiety response produced by sucrose that opposes the
      conditioning of sucrose's positive hedonic response.

PMID- 12062308
TI  - Ingestion of hypertonic NaCl vs. palatable drinks by sodium-depleted rats.
AB  - This work investigated whether the preference for NaCl solution is shifted to
      more palatable solutions in the adult male sodium-depleted rat (n=6-10 per
      group). Animals had daily access to three bottles, one containing water, another
      1.8% NaCl (300 mM), and a third containing 0.9% NaCl (150 mM), Gatorade (orange-
      OG or grape flavored--GG), orange juice (sweetened or unsweetened, from
      concentrate), or 10% sucrose (no sodium). Sodium content in Gatorade and orange
      juice ranged from 7 to 14 mEq/l. Daily intakes were recorded for at least 5 days
      prior to sodium depletion. Then, the animals were depleted of sodium (diuretic
      plus sodium-deficient diet and water for 24 h). Then, the other two bottles were
      returned to the animals and the intakes were recorded for 120 min (sodium
      preference test, SPT). Daily intake from the third bottle (except for unsweetened
      orange juice) at least doubled the daily 1.8% NaCl intake. The average 1.8% NaCl
      intake (13+/-2 ml) in the SPT was higher than the intake of 10% sucrose (6+/-1
      ml) or of any other solution (less than 6 ml). The intakes of 1.8% NaCl and 0.9%
      NaCl (10+/-3 ml) were similar during the SPT. The animals also preferred 0.9%
      NaCl (27+/-1 ml) to OG (3+/-1 ml) in the absence of 1.8% NaCl in the SPT.
      Therefore, the preference for sodium in sodium-depleted rats also applies when
      palatable and nutritive solutions are simultaneously available.

PMID- 12062309
TI  - Passive avoidance response in mice infected with Schistosoma mansoni.
AB  - Schistosomiasis is a parasitic disease of humans and rodents affecting more than
      200 million people worldwide. Following the onset of infection, the worms induce
      granulomas around schistosome eggs in the liver, intestine and central nervous
      system (both brain and spinal cord), which are likely to cause changes in
      cognitive functions. In the present study, CD-1 female mice were percutaneously
      infected with 60 cercariae of Schistosoma mansoni and the effect on the mice's
      cognitive abilities were assessed by using the passive avoidance learning
      paradigm both in an early and a late phase of infection (independent groups). The
      results of the study show that infected animals without brain granulomas (early
      phase) had impairments in their passive avoidance response, whereas mice with
      brain granulomas (late phase) behaved as uninfected ones. Moreover, a decreased
      propensity to start exploration was observed in mice with granulomas in the
      brain. The results suggest that the murine model of infection may be a useful
      tool for studying human neuroschistosomiasis.

PMID- 12062311
TI  - Spontaneous recovery of tolerance to the analgesic effect of morphine.
AB  - There is now substantial evidence that associative processes contribute to the
      development and expression of narcotic tolerance. Like other conditioned
      responses, the compensatory response (CR) thought to mediate tolerance can be
      extinguished by repeatedly presenting the conditioned stimulus (CS, drug-paired
      contextual cues) alone. In the present experiments, rats were used to determine
      if conditioned tolerance to the analgesic effect of morphine would spontaneously
      recover following a sufficient delay between the last extinction trial and
      reexposure to the CS. It was found that tolerance spontaneously recovered 72, but
      not 24 h following the last of nine extinction trials. As well as providing
      support for a Pavlovian model of narcotic tolerance, this finding has important
      clinical implications for cue-exposure drug and alcohol rehabilitation
      strategies.

PMID- 12062310
TI  - Glucocorticoid feedback increases the sensitivity of the limbic system to stress.
AB  - In the hypothalamus, corticotropin-releasing hormone (CRH) has a well-described
      role initiating the hypothalamic-pituitary-adrenal (HPA) axis response to stress.
      Cortisol, released from the adrenal gland, exerts negative feedback on this axis.
      The role of extrahypothalamic CRH in stress responses is less well known. The
      purpose of this study was to measure the response of CRH in the amygdala to acute
      and repeated stress and to examine if cortisol had any effect on this response.
      Immunosensor-based microdialysis probes were used to measure CRH and cortisol in
      the amygdala and cortisol systemically in sheep exposed to a predator stress (a
      dog). Upon presentation of a dog, CRH increased in the amygdala of the sheep and
      then fell off. Cortisol levels rose both systemically and in the amygdala, and as
      they peaked, a second CRH response was observed. Repeated stress changed this
      response, with the magnitude of the first CRH peak decreasing while the second
      peak increased. Repeated stress also produced an exaggeration in both of the CRH
      peaks to presentation of a subsequent novel stress (a forelimb electric shock).
      Animals that had an escape route from the repeated dog stress did not show this
      exaggeration when faced subsequently with the novel stress. Administration of
      mifepristone, a glucocorticoid receptor antagonist, prior to the delivery of the
      repeat stress prevented subsequent changes in the CRH response. The data suggest
      that the amygdala shows a CRH response to presentation of a stressor acutely and
      repeatedly and that repeated stress can alter subsequent amygdala responsiveness
      to the same or a different stressor. This alteration appears dependent on
      circulatory glucocorticoids.

PMID- 12062313
TI  - Food intake and neuronal activation after acute 2DG treatment are attenuated
      during lactation.
AB  - In the present study, we compared the ability of acute peripheral 2-deoxy-
      glucose (2DG) treatment to induce food intake and increase immediate early gene
      expression in lactating versus virgin female rats. In Experiment 1, virgin and
      lactating rats were treated intraperitoneally with either saline or 2DG (400
      mg/kg) and their food intake was compared across the next 6 h. In Experiment 2,
      lactating and virgin rats were given saline or 2DG, sacrificed 1 h later, and
      their brains were processed for Fos-like immunocytochemistry (FLI). The average
      number of cells expressing Fos protein within different brain regions was
      compared among the different groups. Statistical analyses of the data from
      Experiment 1 show that 2DG produces an increase in food intake in virgin rats,
      but not in lactating rats. These data correlate with the results from Experiment
      2, where 2DG treatment resulted in an increase in FLI within the caudal
      ventrolateral medulla (cVLM), the paraventricular nucleus of the hypothalamus
      (PVN), and the supraoptic nucleus of the hypothalamus (SON) of cycling females.
      In lactating rats, however, 2DG failed to increase FLI in these regions.
      Together, these results show that the 2DG-induced food intake response is
      attenuated during lactation and this attenuation is reflected in the activation
      of neuronal groups that are thought to participate specifically in the food
      intake response to glucoprivation. Processes mediating this differential response
      are discussed in terms of the hormonal and metabolic changes that are
      characteristic of lactation.

PMID- 12062312
TI  - Energy metabolism and expression of uncoupling proteins 1, 2, and 3 after 21 days
      of recovery from intracerebroventricular mouse leptin in rats.
AB  - Animals tend to maintain a lower body weight for an extended period after leptin
      administration has ended. This may be due to an enhancement of metabolic rate
      that persists after treatment withdrawal. Our objectives were to determine the
      period of leptin influence, when injected intracerebroventricularly (icv), on
      food intake, body weight, and energy expenditure. Additionally, the relationship
      between expressions of UCP1, UCP2, and UCP3 in different adipose tissues and heat
      production (HP) was assessed. Twenty-four adult male Sprague-Dawley rats were
      injected intracerebroventricularly with either 10 g mouse leptin or 10 l vehicle
      once per day for 4 days. At 24 h after the last injection, one group was killed
      while the other was placed in calorimetry chambers and monitored for 21 days of
      recovery. Leptin-injected rats exhibited an overshoot of food intake and
      respiratory quotient (RQ) during recovery, but body weight remained significantly
      lower up to 6 days. HP decreased in both groups over time but remained higher in
      the leptin group through recovery. However, retained energy (RE) was
      significantly greater than control for about 8 days. Overall, UCP expression was
      reduced at the end of recovery in parallel with the decline in HP. Brown adipose
      tissue (BAT) was the most responsive to leptin administration by dramatically
      changing UCP1 and UCP3 mRNA levels. Our data show that leptin has extended
      effects on energy expenditure but relieves control on food intake and RQ after
      treatment withdrawal. This translated into a reduced positive energy balance that
      slowed body weight recovery.

PMID- 12062314
TI  - Maternal behavior in F344/N and LEW/N rats. Effects on carrageenan-induced
      inflammatory reactivity and body weight.
AB  - Inbred Fischer (F344/N) and Lewis (LEW/N) rats differ on a myriad of behavioral
      and physiological endpoints, such as inflammatory, startle and drug responsivity.
      These differences point to underlying genetic differences between the strains.
      However, genetic models of hypertension have shown the importance of the maternal
      environment in the development of high blood pressure, suggesting that maternal
      influences might also play a role in adult phenotypes of the LEW/N and F344/N
      strains. This was tested in the present series of experiments in which the
      effects of crossfostering on carrageenan-induced inflammation and on body weight
      were examined in the two strains. Following the demonstration that the two
      strains differed in maternal behavior (Experiment 1), which was independent of
      the pup being reared (Experiment 2), crossfostered and in-fostered pups from the
      LEW/N and F344/N strains were injected with carrageenan (at 60 days of age) and
      subsequently assessed for the accumulation of exudate in response to the
      injection. Body weights were also monitored from birth through 60 days of age.
      Although crossfostering affected body weight of the two strains, specifically,
      reducing weights in LEW/N pups reared by F344/N dams and increasing weights of
      F344/N pups reared by LEW/N dams, crossfostering did not affect inflammatory
      reactivity to carrageenan. Specifically, LEW/N pups had a greater level of
      exudate than F344/N pups, independent of the conditions under which they were
      reared, suggesting that differences in the inflammatory response between these
      two strains are under a high degree of genetic control. These results were
      discussed in terms of genetic factors mediating the early form of immune
      reactivity induced by carrageenan.

PMID- 12062315
TI  - Rat sex and strain differences in responses to stress.
AB  - Sensitivity to stress has been linked to the development of a variety of physical
      and psychological disorders. Studies to-date have focused on extreme stress
      phenotypes, have studied mostly male responses, have used limited dependent
      variables, and have included a limited number of measurement time points. The
      present experiment was designed to address these limitations. Feeding, body
      weight, open-field activity, acoustic startle reflex (ASR), and prepulse
      inhibition (PPI) responses of adult male and female Sprague-Dawley and Long-Evans
      rats to daily immobilization stress (20 min/day) were evaluated for 3 weeks.
      Stress significantly decreased feeding and body weight of males but generally not
      of females. Effects were greatest in Long-Evans males. Stress decreased 15-min
      activity levels for males on Stress Day 1, but not on other days. Stress did not
      affect 15-min activity levels of Long-Evans females but decreased 15-min activity
      levels of Sprague-Dawley females on every measurement day. ASR responses to
      stress differed based on rat strain; percent PPI responses differed based on rat
      strain and sex. Stress increased startle responses of Sprague-Dawley males and
      females but not of Long-Evans males and females. Stress reduced PPI of Long-Evans
      females on every measurement day but not of other groups. These findings indicate
      that strain and sex of rat is important to consider in evaluating behavioral and
      physiological responses to stress.

PMID- 12062316
TI  - Melatonin promotes sleep in three species of diurnal nonhuman primates.
AB  - Nocturnal melatonin secretion is concurrent with consolidated sleep episodes in
      diurnal mammals and physiological melatonin levels can promote sleep onset in
      humans and in pigtail macaques. In order to further investigate the effects of
      melatonin treatment on sleep parameters in diurnal nonhuman primates, three
      macaque species have been studied: Macaca nemestrina, Macaca fascicularis, and
      Macaca mulatta. Sleep was assessed using continuous actigraphic recording of
      motor activity in animals maintained under 12:12-h light/dark cycle. Oral doses
      of melatonin (5-320 microg/kg) were administered 2 h before lights-off time, with
      5- and 10-microg/kg doses resulting in physiological circulating melatonin levels
      (31-95 pg/ml). The effects of melatonin administration were similar in three
      species studied and included significantly earlier sleep onset time and longer
      sleep period time, with no difference in time of awakening, following
      administration of both physiological (5-10 microg/kg) and pharmacological (20-320
      microg/kg) doses. While low melatonin doses (5-20 microg/kg) did not
      significantly affect nighttime sleep efficiency, higher pharmacological doses
      reduced sleep efficiency and increased sleep fragmentation at night, and reduced
      spontaneous daytime locomotor activity. Daily administration of a 5-microg/kg
      dose for 4 weeks or gradually escalating melatonin doses (5-320 microg/kg over a
      3-week period) did not result in the development of tolerance or sensitization to
      the effect of melatonin on sleep initiation or sleep period. These data affirm
      that sleep-promoting effects of melatonin observed in humans are also typical for
      diurnal primates. They also suggest that physiological and pharmacological
      melatonin levels might produce different effects on sleep efficiency and that
      nonhuman primates can serve as adequate animal model for studying the mechanisms
      of melatonin's action on sleep and performance.

PMID- 12062317
TI  - Central administration of zinc reduces salt intake in rats.
AB  - The aim of the present study was to investigate the effect of third ventricle
      injections of zinc on salt intake in rats in the three different experimental
      models where sodium appetite is increased: fluid deprivation, central
      angiotensinergic stimulation and sodium depletion. Adult Wistar male rats
      received third ventricle injections of Zn(Ac)2 in three different doses (0.03,
      0.3 and 3.0 nmol/rat). Central angiotensinergic stimulation was achieved by third
      ventricle injections of angiotensin II in the dose of 25 ng/rat 30 min before
      central zinc administration. As expected, fluid deprivation, central
      angiotensinergic stimulation and sodium depletion significantly increased sodium
      appetite. Water intake was also enhanced after fluid deprivation and central
      angiotensinergic stimulation. After sodium depletion, no increase in water intake
      was observed. Third ventricle injections of zinc inhibited salt intake in all
      three experimental models studied. Water intake was also inhibited by central
      zinc administration after fluid deprivation and central angiotensinergic
      stimulation. Conversely, third ventricle injections of zinc were unable to modify
      food intake or body temperature. It is suggested that zinc, acting on central
      structures related to the control of body fluid homeostasis, inhibits the drive
      for salt intake that is normally observed during fluid deprivation, central
      angiotensinergic stimulation and sodium depletion.

PMID- 12062318
TI  - Effects of withdrawal from anabolic androgenic steroids on aggression in adult
      male rats.
AB  - In gonadally intact male rats, chronic exposure to high levels of testosterone
      propionate (TP) increases aggression, nandrolone (ND) has little effect and
      stanozolol (ST) suppresses aggression. The present experiment tested whether the
      effects of TP, ND and ST on aggression and reproductive tissues are reversed
      following anabolic androgenic steroid (AAS) withdrawal. Gonadally intact males
      received TP, ND, ST or vehicle for 12 weeks. Injections were then discontinued.
      Aggression was tested 3 weeks (short term) and 12 weeks (long term) after
      withdrawal of AAS treatment, with either a gonadally intact or a castrated
      opponent in three different environments (home, opponent's and neutral cage).
      After short-term withdrawal, some parameters of aggression were significantly
      above control levels in TP males. There were no significant differences between
      ND or ST males and controls, though ST males showed the lowest levels of
      aggression. No significant differences between any of the groups were found after
      long-term withdrawal. Eighteen weeks after AAS withdrawal, serum testosterone (T)
      and LH levels were comparable to controls in all groups. Testes weights were at
      control levels in ST males, but significantly higher than controls in TP and ND
      males. Seminal vesicle weights were significantly elevated in TP males, but
      similar to controls in both ND and ST males. None of the prostate weights were
      significantly different from controls. These results suggest that aggression
      gradually returns to normal following withdrawal from AAS. Some, if not all,
      hormone levels and tissue weights return to normal, suggesting possible long
      lasting effects of chronic AAS exposure.

PMID- 12062319
TI  - Nest building in nulligravid, primigravid and primiparous C57BL/6J and DBA/2J
      mice (Mus musculus).
AB  - C57BL/6J (B6) and DBA/2J (D2) mice differ in maternal behavior and nest building,
      but previous observations on nest building appear to be contradictory. Lactating
      B6 females spent more time nest building than lactating D2 females [Physiol.
      Behav. 67 (1999) 599.]; however, pregnant D2 females have been reported to build
      better nests than pregnant B6 females [Physiol. Behav. 29 (1982) 153.]. To
      resolve this apparent discrepancy, virgin B6 and D2 females were mated, and the
      nest quality of nulligravid, primigravid and lactating primiparous females was
      compared between groups and with that of virgin females. There were no strain
      differences in the nest ratings of virgin or mated nulligravid females, nor did
      these groups differ within strains. Pregnant and lactating females of both
      strains built better nests than nonpregnant females. There was an increase in
      nest ratings in both strains on the day of parturition. The nest ratings of
      pregnant and lactating females were higher in B6 than D2 females. The largest
      strain differences were observed between pregnant B6 and D2 females. One
      hypothesis to account for these results is that females of these two strains
      differ in their levels of or sensitivity to hormones during pregnancy and
      parturition.

PMID- 12062320
TI  - Exogenous testosterone, aggression, and mood in eugonadal and hypogonadal men.
AB  - To investigate (1) the effects of exogenous testosterone (T) on self- and partner
      reported aggression and mood and (2) the role of trait impulsivity in the T
      aggression relationship. Thirty eugonadal men with partners were randomized into
      two treatment groups to receive: (1) 200 mg im T enanthate weekly for 8 weeks or
      (2) 200 mg im sodium chloride weekly for 8 weeks. Eight hypogonadal men received
      200 mg im T enanthate biweekly for 8 weeks. All groups completed a battery of
      behavior measures at baseline (Week 0) and at Weeks 4 and 8. Cognitive and motor
      impulsivity were the only predictors of self-reported total aggression (over and
      above age and T levels) at Weeks 0, 4, and 8. No significant changes in
      aggression or mood levels were found in the eugonadal-treated group. Significant
      reductions in negative mood (tension, anger, and fatigue) followed by an increase
      in vigor were found in response to T treatment in the hypogonadal group. These
      results demonstrate that inability to control one's behavior when such control is
      required by a particular situation (impulsivity) was found to significantly
      predict levels of aggression over and above age and T level. These data do not
      support the hypothesis that supraphysiological levels of T (within this range)
      lead to an increase in self- and partner-reported aggression or mood
      disturbances. Instead, for the first time, this study has identified the high
      level of negative affect experienced by hypogonadal patients. These findings have
      implications for T replacement therapy and male contraception.

PMID- 12062321
TI  - Intake inhibition by NPY: role of appetitive ingestive behavior and aversion.
AB  - Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female
      rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution
      of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of
      times the rats visit a bottle filled with sucrose (appetitive behavior). In this
      study, we investigated if the suppression of consummatory behavior was dependent
      upon the increase of appetitive behavior. The shift from consummatory to
      appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to
      the sucrose solution in the bottle. However, the intraoral intake of the sucrose
      solution was still decreased in NPY-treated rats. NPY did not modify taste
      reactivity as measured by aversive responses during continuous intraoral infusion
      of sucrose or ingestive and aversive responses to brief intraoral infusion of
      sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a
      bottle and intake from the bottle and inhibited sexual behavior in male rats but
      had no effect on the sexual behavior in the absence of a bottle. The visits and
      the intake were suppressed, but sexual behavior was not activated by adding QHCl
      (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior,
      therefore, does not indiscriminately facilitate consummatory behavior. Male rats
      showed aversive or ingestive behavior and sexual behavior simultaneously during
      intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases
      intraoral intake and increases appetitive ingestive behavior via partially
      separable mechanisms that are independent of taste aversion.

PMID- 12062322
TI  - Protein is more potent than carbohydrate for reducing appetite in rats.
AB  - The purpose of this study was to characterize further the effects of loads of
      protein versus carbohydrate on subsequent food intake in rats. We used an
      intraoral cannula to deliver isoenergetic isovolumic loads, in a tightly
      controlled time frame allowing for both metabolic responses and orosensory
      components of the load. Our results showed that the gluten load (GLT-100%)
      induced a greater depression in food intake than an isocaloric wheat starch load
      (GLT-0%). The types of protein used in the load (total milk protein vs. GLT) did
      not seem to influence their appetite-suppressive effect. There was a dose
      dependent effect of the satiating effects of the protein loads, the GLT-100% load
      being more effective than either the GLT-35% or GLT-50% loads. Pattern analysis
      of the meal following the load suggested that animals were more satiated by
      protein, at least when loads contained 35% or 50% of protein, than by
      carbohydrate. At least 1 day was necessary before we saw a significant decrease
      in the energy intake following the protein loads. Thus, the animals had to learn
      the postingestive effects of the loads before the response stabilized. Taken
      together, the present results confirm that protein has a greater satiating effect
      than carbohydrate and extend these results by revealing that the larger the
      proportion of protein in the food, the larger the satiating effect, and that the
      quality of protein does not seem to play a significant role.

PMID- 12062323
TI  - The effect of Type I diabetes on the eating patterns of free-living French: a
      diet diary study.
AB  - In order to investigate the changes produced by Type I diabetes on the ad libitum
      eating behavior of free-living humans, 56 French participants with diabetes and
      28 healthy controls were paid to maintain detailed food intake diaries for four 7
      day periods. The participants with diabetes ate more protein and more frequent
      meals, ate slightly later and with fewer other people, were less hungry, thirsty,
      and depressed, but more elated than the healthy participants. Responses to social
      facilitation, the diurnal rhythm, subjective hunger, the palatability of the
      food, and the weekend were not affected by the presence of diabetes. The
      participants with diabetes had significantly larger correlations and regression
      coefficients for the relationship between meal size and the duration of the
      before-meal interval. The relationship between meal size and the after-meal
      interval was strong and positive in all participants. The recorded behavioral
      characteristics of diabetics may, in part, be accounted for by the nutritional
      education that is provided as an integral part of treatment. Based upon these
      results, it was theorized that the glucose regulatory system is an influence on
      intake, but only one of many that are responsible for the coordination, control,
      and regulation of nutrient intake in free-living humans.

PMID- 12062324
TI  - Effects of amylin and salmon calcitonin on feeding and drinking behavior in pygmy
      goats.
AB  - In the present study, the effects of peripherally administered amylin and of the
      amylin-related peptide salmon calcitonin (sCT) on food and water intake was
      tested for the first time in pygmy goats. In the first series of experiments, the
      effect of amylin on food (0.5, 1.0 and 2.0 microg/kg b.wt.) and water (2.0
      microg/kg) intake was tested. In the second series of experiments, the effect of
      sCT on food intake (1.0 microg/kg) was tested under ad libitum feeding conditions
      or after 14 h food deprivation. The relationship of dose on the effect of sCT
      (0.1, 0.5 and 1.0 microg/kg) on food and water intake was also tested. Finally,
      the effect of a low dose (0.1 sCT microg/kg) on water intake was also
      investigated during food withdrawal. We showed for the first time an anorexigenic
      effect of the satiety peptide amylin (2.0 microg/kg) in ruminants, which was
      characterized by a reduction in meal size. In pygmy goats, the administration of
      the three doses of sCT induced an anorexigenic effect, which was larger and of
      longer duration when compared with amylin, although the anorexigenic effect of
      the lowest dose never reached significance. This effect was not dose dependent
      and was partly due to a reduction in meal size and partly to a prolongation of
      the interval between meals. The anorexigenic effect of sCT was accompanied by a
      reduced water intake, probably due to reduced prandial drinking. Furthermore, the
      low dose of sCT (0.1 microg/kg) was dipsogenic during food withdrawal.

PMID- 12062326
TI  - Spotlight on atrial fibrillation-the 'complete arrhythmia'.

PMID- 12062327
TI  - Mother rotors and fibrillatory conduction: a mechanism of atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and the
      major cardiac cause of stroke. Recent studies in patients with paroxysmal AF have
      shown that the arrhythmia is triggered by focal sources localized usually in one
      of the cardiac veins. However, in chronic AF, the prevailing theory is that
      multiple random wavelets of activation coexist to create an unorganized atrial
      rhythm. Experiments in isolated hearts have demonstrated that stable, self
      sustained rotors can exist in the atria and that high frequency activation by
      such rotors results in the complex patterns of activation that characterize AF.
      Studies in animals and patients support the view that at least some cases of
      paroxysmal and chronic AF are the result of the uninterrupted periodic activity
      of discrete reentrant sites. In this brief review article, we examine historical
      data and more recent experimental evidence behind the hypothesis that AF may be
      organized by one, or a small number of high-frequency reentrant sources localized
      in the left atrium. We then discuss the potential implications and evidence
      supporting such a hypothesis for human AF. Finally, we suggest future studies
      designed to unravel the detailed molecular, cellular and pathophysiological
      mechanisms responsible for AF initiation and maintenance. The work discussed may
      open potentially exciting new diagnostic and therapeutic possibilities.

PMID- 12062328
TI  - Mechanisms of atrial flutter and atrial fibrillation: distinct entities or two
      sides of a coin?

PMID- 12062329
TI  - Electrical, contractile and structural remodeling during atrial fibrillation.
AB  - The natural history of atrial fibrillation (AF) is characterized by a gradual
      worsening with time. The recent finding that AF itself produces changes in atrial
      function and structure has provided a possible explanation for the progressive
      nature of this arrhythmia. Electrical remodeling (shortening of atrial
      refractoriness) develops within the first days of AF and contributes to an
      increase in stability of AF. However, 'domestication of AF' must also depend on a
      'second factor' since the persistence of AF continues to increase after
      electrical remodeling has been completed. Atrial contractile remodeling (loss of
      contractility) leads to a reduced atrial transport function after cardioversion
      of AF. An important clinical consequence is that during several days after
      restoration of sinus rhythm, the risk of atrial thrombus formation is still high.
      In addition, the reduction of atrial contractility during AF may enhance atrial
      dilatation which may add to the persistence of AF. Tachycardia-induced structural
      remodeling takes place in a different time domain (weeks to months). Myolysis
      probably contributes to the loss of atrial contractile force. Although it might
      explain the loss of efficacy of pharmacological cardioversion and the development
      of permanent AF, the role of structural remodeling in the progression of AF is
      still unclear. Atrial structural remodeling also occurs as a result of heart
      failure and other underlying cardiovascular diseases. The associated atrial
      fibrosis might explain intra-atrial conduction disturbances and the
      susceptibility for AF. Thus, both AF itself and the underlying heart disease are
      responsible for the development of the arrhythmogenic substrate. New strategies
      for prevention and termination of AF should be build on our knowledge of the
      mechanisms and time course of AF-induced atrial remodeling.

PMID- 12062330
TI  - Signal transduction systems and atrial fibrillation.
AB  - Cell communication, an essential component of integrated physiological function
      in multicellular organisms, is mediated largely through informational molecules,
      such as hormones and neurotransmitters. After binding to specific receptors,
      these first messengers activate intracellular signaling cascades and, thereby,
      translate extracellular messenger levels into intracellular events. Atrial
      fibrillation is associated with significant electrophysiological and structural
      alterations of atrial tissue. Most of these changes seem to be related to
      activation of signal transduction systems at the molecular atrial level. This
      review will describe the role and regulation of different signal transduction
      systems in fibrillating atria.

PMID- 12062331
TI  - Cellular electrophysiology of atrial fibrillation.

PMID- 12062332
TI  - Cardiac gap junctions and connexins: their role in atrial fibrillation and
      potential as therapeutic targets.
AB  - In the heart, changes in velocity and in patterns of conduction of myocardial
      electrical activity can affect cardiac rhythm and the coordination of
      contraction. Abnormal electrical coupling between cardiomyocytes through gap
      junctions is, therefore, considered an important factor in various
      pathophysiologic conditions. In the present report we summarize the literature on
      gap junctions and their structural proteins, the connexins, in the normal and
      fibrillating atrium. Putative implications of the recently reported remodelling
      of atrial gap junctions for stability of the arrhythmia will be discussed. Also
      the reversibility of the remodelling process will be addressed in the light of a
      potentially new therapeutic target for controlling the progression of atrial
      fibrillation (AF).

PMID- 12062333
TI  - Transgenic and knockout mouse models of atrial arrhythmias.
AB  - While much has been learned about atrial fibrillation from large animal models,
      many of these studies are correlative. Genetically-altered mouse models have
      provided much information about such genetic diseases as the long QT syndrome,
      but have to date not been utilized much to study atrial fibrillation. The ability
      to study the importance of a single gene product in pathophysiology make this a
      potentially powerful tool to understand the causal relationship of several
      proteins and the substrate for atrial fibrillation. In this manuscript we review
      the techniques available to study atrial electrophysiology and some of the
      genetically-altered mouse models that have implications for atrial fibrillation.

PMID- 12062334
TI  - Basic and clinical electrophysiology of pulmonary vein ectopy.
AB  - In a subset of patients, atrial fibrillation is caused by rapidly firing foci
      that are often located in the pulmonary veins especially when fibrillation is
      paroxysmal. Histologic data show that myocardial tissue of the left atrial wall
      extends into the pulmonary venous walls. Both in dog and human pulmonary veins,
      arrangement of the myofibers is complex. Clinical and animal studies reveal both
      double potentials and fractionated electrograms in the pulmonary veins, which are
      related to the complex architecture of the myocardial sleeves in the veins. Such
      a structure supports the occurrence of reentry. As well, the reduced coupling of
      cells at sites with abrupt changes in fiber direction could facilitate the escape
      of a focus and subsequent activation of surrounding tissue. Intracellular
      recordings made in the pulmonary veins of guinea pig and dog hearts showed that
      spontaneous activity can occur. Spontaneous action potentials with phase 4
      depolarization as well as early after depolarizations were observed in these
      animal models. In non-spontaneously active preparations, spontaneous activity
      could be provoked by pharmacologic interventions. The cycle length of bursts of
      ectopic beats arising in the pulmonary veins of man is often irregular,
      supporting a focal mechanism of the ectopic beats. The anisotropic
      characteristics of the myocardial sleeves in the veins may increase the ability
      of a focus to become evident.

PMID- 12062335
TI  - Thoracic veins and the mechanisms of non-paroxysmal atrial fibrillation.
AB  - OBJECTIVE: The purpose of this article is to review the importance of thoracic
      veins in the maintenance of sustained (non-paroxysmal) atrial fibrillation (AF).
      METHODS: Thoracic veins, including the pulmonary veins (PVs), vein of Marshall
      (VOM) and the superior vena cava (SVC), have muscle sleeves that connect to the
      atria. It is well known that electrical activities can be recorded within these
      venous structures. In some incidences, these thoracic veins may serve as the
      trigger and/or the substrate for paroxysmal AF. The importance of thoracic veins
      in chronic (sustained) AF is less well appreciated. Therefore, we review the
      literature to determine if thoracic veins are important in the maintenance of
      sustained AF. RESULTS: Our recent study demonstrated that repetitive rapid
      electrical activities are present in the PVs and in the VOM during pacing-induced
      sustained AF in dogs. Because of these repetitive rapid activities, these
      thoracic veins have shorter activation cycle lengths than that of the left
      atrium, which, in turn, has shorter cycle lengths than that of the right atrium.
      Others have demonstrated that PV isolation in humans can result in a cure of
      sustained human AF in >80% of patients undergoing concomitant surgery.
      CONCLUSION: These findings suggest that repetitive rapid activities within the
      thoracic veins may be responsible for the maintenance of non-paroxysmal
      (sustained) AF.

PMID- 12062336
TI  - Electrophysiological properties of the human atrium in atrial fibrillation.
AB  - It has been reported that ectopic foci from the pulmonary veins can initiate
      atrial fibrillation (AF) and can also act as drivers for maintaining AF. However,
      not all patients with atrial arrhythmias initiate AF. A substrate for atrial
      propensity to AF is required for AF initiation and maintenance. Thus, we reviewed
      and discussed mainly the electrophysiological properties observed in AF. Abnormal
      atrial electrograms during sinus rhythm and abnormal responses of the atrium
      elicited by programmed stimulation have been observed more frequently in patients
      with paroxysmal AF than in those without. A shorter atrial effective refractory
      period, greater dispersion of the atrial refractoriness and atrial conduction
      delay are also of electrophysiologic significance in the genesis of AF.
      Electrical remodeling is likely to be a final common pathway that ultimately
      supervenes. Even if atrial electrical remodeling facilitates AF initiation and AF
      perpetuation, the initiation of AF requires a trigger. Further investigation into
      the electrophysiological properties in AF will be needed in order to contribute
      to the future development of an appropriate treatment.

PMID- 12062337
TI  - Molecular mechanisms of remodeling in human atrial fibrillation.
AB  - An important acknowledgement of the last several years is that atrial
      fibrillation (AF) modifies the electrical properties of the atrium in a way that
      promotes its occurrence and maintenance. This arrhythmogenic electrophysiological
      remodeling is well established, but can not explain by itself that 'AF begets
      AF'. This review describes molecular changes involving rapid functional
      alterations and slower changes in protein expression that cause electrical
      remodeling and contractile dysfunction in AF. An important molecular feature of
      AF is the reduction in L-type Ca(2+) channel function and protein expression.
      This reduction may serve to protect the cell against a potentially lethal Ca(2+)
      overload resulting from the increased activation rate in AF. Further, the review
      discusses the possible role of proteolytic systems, notably the calpains, as a
      mechanism linking Ca(2+) overload to reduced protein expression. Thus, it appears
      that the elaborate molecular changes in AF are directed primarily at protecting
      the myocyte from cellular stress. However, such early protection occurs at the
      expense of electrophysiological changes that promote the long-term maintenance of
      AF.

PMID- 12062338
TI  - Atrial structure and fibres: morphologic bases of atrial conduction.
AB  - The relationship between anatomy and function has long been recognised.
      Understanding the gross structure, and the myoarchitecture, of the atriums is
      fundamental to investigations into the substrates and therapy of atrial
      fibrillation. Based primarily on our experience with normal human hearts, this
      review provides, firstly, a basis of comparison of gross structures as seen in
      the clinical situation, and in animals commonly used in experimental studies.
      Secondly, we discuss the general arrangement of myocardial fibres with respect to
      gross topography in the normal human heart. The right atrium is dominated by an
      extensive array of pectinate muscles within the extensive appendage, whereas the
      left atrium is relatively smooth-walled, with a much smaller tubular appendage.
      Myoarchitecture displays parallel alignment of fibres along distinct muscle
      bundles, such as the terminal crest and Bachmann's bundle. Within the smooth wall
      of the left atrium, there is a marked transmural change in the orientation of the
      muscular fibres. Abrupt changes in orientation, and mixed arrangements, are
      common between bundles. Other than Bachmann's bundle, the muscular bridges which
      provide interatrial connections, and connections between the left atrium and the
      coronary sinus and inferior caval vein, are highly variable. Inhomogeneities both
      in gross structure and myoarchitecture are common in the normal heart. These
      should be taken into account when investigating hearts from patients known to
      have had a history of arrhythmias, in devising computer models, or when refining
      diagnostic and therapeutic strategies.

PMID- 12062339
TI  - Ablation therapy for atrial fibrillation (AF): past, present and future.
AB  - Atrial fibrillation, the most common arrhythmia, is frequently disabling and drug
      resistant. Non-pharmacological approaches including surgery and catheter-based
      ablation have been developed for the most symptomatic patients. These new
      treatment strategies have dramatically increased our knowledge of the
      pathophysiology of this arrhythmia but most importantly demonstrated that atrial
      fibrillation is curable. These approaches are far from being perfect but good
      enough to be offered in routine practice to selected patients in experienced
      centers. The importance of pulmonary veins in the initiation of AF has clearly
      been demonstrated and their role in maintaining AF is likely. Most of the
      curative approaches are therefore based on their isolation. Future technical
      improvements based on presently applied concepts are likely to widen the
      indications for ablation therapy of AF.

PMID- 12062340
TI  - Therapeutic implications of atrial fibrillation mechanisms: can mechanistic
      insights be used to improve AF management?
AB  - Atrial fibrillation (AF) is a very common clinical problem, and presently
      available treatment options are suboptimal. A tremendous amount has been learned
      over the past 10 years about the atrial substrates that support sustained AF at
      the tissue, ionic and molecular levels. This understanding of the fundamental
      mechanisms underlying AF has opened up a variety of new, rationally-based
      therapeutic approaches. The present paper reviews what is known about the
      mechanistic substrates that lead to AF and discusses the potential therapeutic
      consequences.

PMID- 12062341
TI  - Structural correlate of atrial fibrillation in human patients.
AB  - OBJECTIVE: We tested the hypothesis that structural remodeling of cellular
      connections, alterations in the expression of connexins (Cx), and an increase in
      fibrosis represent anatomic substrates of atrial fibrillation (AF). METHODS: In
      31 patients with AF undergoing a Maze procedure and 22 patients in sinus rhythm
      (SR), biopsies were taken intraoperatively from the right atrial (RA) free wall
      and appendages and investigated with immunoconfocal and electron microscopy.
      RESULTS: All patients with AF exhibited a concomitant lateralization of gap
      junctional proteins Cx43 and Cx40, and N-cadherin (the major mechanical junction
      protein), instead of being confined to the intercalated discs, as observed in SR.
      These results were confirmed by quantitative immunoconfocal analysis and electron
      microscopy. Among diverse junctional proteins, in AF, Cx40 was markedly
      heterogeneous in distribution. As compared with the SR group, Cx43 was
      significantly decreased in AF by 57% in RA appendages and by 56% in RA free wall.
      Cx40 was reduced by 54% in appendages, but had a tendency to be increased in the
      RA free wall. Collagen I was significantly higher in AF than in SR by 48% in RA
      appendages and by 69% in the RA free wall tissues. CONCLUSIONS: The structural
      correlate of AF comprises extensive concomitant remodeling of mechanical and
      electrical junctions, reduction of Cx43, heterogeneous distribution of Cx40 in
      terms of different amounts of Cx40 in different RA tissues or in spatially
      adjacent regions of atrial myocardium. These changes, together with augmentation
      of fibrosis, may underlie localized conduction abnormalities and contribute to
      initiation and self-perpetuation of re-entry pathways and AF.

PMID- 12062342
TI  - Activation of proteolysis by calpains and structural changes in human paroxysmal
      and persistent atrial fibrillation.
AB  - OBJECTIVE: Atrial fibrillation (AF) is accompanied by electrical, structural and
      ion-channel protein remodeling. We tested if proteolysis by calpain and
      proteasome is activated during AF, and studied the relation with the remodeling
      processes. METHODS: Right atrial appendages were obtained from patients with
      paroxysmal (n=7) or persistent (n=10) lone AF and compared to controls (n=10) in
      sinus rhythm undergoing coronary artery bypass grafting (CABG). Proteolysis was
      measured using Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. Protein expression
      of calpain I and II was assessed by Western-blot and calpain I localization by
      immunohistochemistry. Structural changes were quantified by counting atrial
      myocytes with contraction bands or hibernation. RESULTS: Calpain activity was
      significantly increased in paroxysmal AF (2-fold, P<0.001) and persistent AF (3
      fold, P<0.001), mainly due to calpain I activation. Increased calpain I protein
      expression was found in AF with Western blot and immunohistochemistry. Myocytes
      from all AF groups showed increased contraction bands, whereas hibernation was
      only found in persistent AF. Calpain activity correlated with L-type Ca(2+)
      channel and Kv1.5 protein amounts (r=-0.80, P<0.001 and r=-0.72, P<0.001,
      respectively), degree of structural changes (r=0.90, P<0.001), shortening of
      atrial effective refractory period (AERP) (basic cycle length 500 ms, r=-0.60,
      P<0.001) and AERP rate adaptation (r=-0.80, P<0.001). CONCLUSIONS: Calpain
      activity is induced during AF and correlates with parameters of ion-channel
      protein, structural and electrical remodeling. The results suggest that calpain
      activation represents an important mechanism linking calcium overload to cellular
      adaptation mechanisms in human AF.

PMID- 12062343
TI  - Determinants and consequences of atrial fibrosis in patients undergoing open
      heart surgery.
AB  - OBJECTIVE: Atrial fibrillation (AF) is a frequent complication following open
      heart surgery (OHS). Increased atrial fibrosis may indicate the presence of an
      intrinsic arrhythmogenic substrate. The aim of this prospective study was to
      determine whether atrial fibrosis is associated with increased prevalence of AF
      after OHS. METHODS: Right atrial appendages were obtained from 259 patients
      undergoing OHS; none of the patients had a history of AF. Atrial fibrosis was
      quantitatively analyzed with point counting. All patients were followed
      prospectively until hospital discharge. None of the patients received anti
      arrhythmic prophylaxis. Post-operative AF was defined as an episode of AF lasting
      > or = 5 min. RESULTS: Quantitation of atrial fibrosis yielded a mean volume
      percentage of 15.8 +/- 4.3% (V%; range 4.6-32.4%). Patient age was found to
      correlate with the amount of atrial fibrosis (r = 0.165; P < 0.01) and surface P
      wave duration (r = 0.249; P < 0.01). The degree of fibrosis combined with P-wave
      duration predicted post-operative AF (P < 0.01). Age (> 60 years) and P-wave
      duration (> or = 100 ms) were independent predictors of post-operative AF (age:
      relative risk 2.20; P-wave: relative risk 2.69; P < 0.05). The patients were
      divided into three groups: group 1, V% = 4.6-13.8%; group 2, V% = 13.9-23.1%;
      group 3, V% = 23.2-32.4%. A total of 52 patients (20.1%) developed AF, which
      occurred least commonly in group 1 (16.3%) and group 2 (21.2%) as compared with
      group 3 (33.3%). CONCLUSIONS: Atrial fibrosis provides a pathophysiological
      substrate for post-operative AF. The results support the importance of P-wave
      duration as a predictor of post-operative AF, and explain the increased
      prevalence of AF in elderly patients after OHS.

PMID- 12062345
TI  - Density and function of inward currents in right atrial cells from chronically
      fibrillating canine atria.
AB  - OBJECTIVE: To determine whether I(Na) and I(CaL) are altered in function/density
      in right atrial (RA) cells from dogs with chronic atrial fibrillation (cAF dogs,
      episodes lasting at least 6 days) and whether the changes that occur differ from
      those in dogs with nonsustained or brief episodes of fibrillation (nAF dogs).
      METHODS: Using whole cell voltage clamp, sodium and calcium current density and
      function were determined in disaggregated RA cells from nAF, cAF and control
      atria (Con). Ca(2+) currents were studied with either Ca(2+) or Ba(2+) as charge
      carrier, as well as with either EGTA or BAPTA as the internal solution Ca(2+)
      chelator. RESULTS: After rapid atrial pacing, dogs can either fibrillate for
      short periods of time (nAF) or longer, more sustained periods (cAF). Both the
      Na(+) and Ca(2+) current decrease in cells of the nAF atria. Na(+) current
      density remains reduced in cAF cells with some slowing of recovery kinetics.
      Ca(2+) current density does not further decrease with persistent atrial
      fibrillation (cAF cells) remaining significantly different from Con cells.
      However, the difference in density of Ca(2+) currents between nAF and Con cells
      is negligible when Ba(2+) is charge carrier and when Ca(i) is quickly and
      effectively chelated with BAPTA. On the contrary, cAF I(BaL) densities remain
      significantly reduced compared to Con and nAF values when Ba(2+)/BAPTA conditions
      are used. CONCLUSIONS: Na(+) current density/function does not recover to Con
      values in cAF. Further these enhanced Ca(2+)-dependent inactivation processes
      contribute significantly to the reduction of I(CaL) density observed in nAF cells
      while reduction of Ca(2+) currents in cAF atria is probably by another mechanism

PMID- 12062344
TI  - Human inward rectifier potassium channels in chronic and postoperative atrial
      fibrillation.
AB  - OBJECTIVE: We showed recently that the 825T allele of the G-protein beta 3
      subunit C825T polymorphism is associated with large inward rectifier K(+)
      currents I(K1) but low acetylcholine-activated K(+) current I(K,ACh) amplitudes.
      During chronic atrial fibrillation (AF), I(K1) and I(K,ACh) current densities
      were increased when compared to sinus rhythm (SR). It is unknown whether chronic
      AF and G beta 3 gene status are independent contributors to atrial K(+) current
      activity. We measured I(K1) and I(K,ACh) in tissue from AF patients with
      different G beta 3 genotypes and assessed the relation between the I(K1) and
      I(K,ACh) amplitudes and the incidence of postoperative AF. METHODS: We measured
      the amplitudes of I(K1) and I(K,ACh) in atrial myocytes from 26 patients with
      sinus rhythm (SR) and from 16 patients with chronic AF (>6 months). The K(+)
      currents were measured with standard patch-clamp techniques. The G beta 3 gene
      status of the patients was determined by PCR and restriction analysis. RESULTS:
      At -100 mV, the amplitude of I(K1) was larger in AF (10.9+/-1.0 pA/pF, n=49/16,
      cells/patients) than in SR (6.3+/-0.6 pA/pF, n=68/26, P<0.05), whereas the
      amplitude of I(K,ACh) was smaller in chronic AF (2.9+/-0.7 pA/pF, n=49/16) than
      in SR (6.3+/-0.7 pA/pF, n=68/26, P<0.05). These changes were independent of the
      patient G beta 3 gene status. Eight patients out of 26 in the SR group (31%)
      developed postoperative AF. When analysed based on incidence of postoperative AF,
      current amplitudes did not differ significantly. CONCLUSION: We provide evidence
      for up-regulation of I(K1) but down-regulation of I(K,ACh) in chronic AF which
      are independent of G beta 3 gene status. Atrial myocytes from patients who are in
      SR but later develop postoperative AF have no manifestation of altered I(K1) and
      I(K,ACh) at the time of cardiac surgery. Our results suggest that the AF-related
      changes of I(K1) and I(K,ACh) may be a consequence of or a contributory factor to
      chronic AF.

PMID- 12062346
TI  - Remodeling of Ca(2+)-handling by atrial tachycardia: evidence for a role in loss
      of rate-adaptation.
AB  - BACKGROUND: Loss of rate-dependent action potential (AP) duration (APD)
      adaptation is a characteristic feature of atrial tachycardia-induced remodeling
      (ATR). ATR causes sarcolemmal ion-channel remodeling (ICR) and changes in Ca(2+)
      handling. The present studies were designed to quantify Ca(2+)-handling changes
      and then to apply a mathematical AP model to assess the contributions of Ca(2+)
      handling abnormalities and ICR to loss of APD rate-adaptation. METHODS: Indo-1
      fluorescence was used to measure intracellular Ca(2)-transients and whole-cell
      patch-clamp to record APs in atrial myocytes from control dogs and dogs subjected
      to atrial pacing at 400/min for 6 weeks. A previously developed ionic model of
      the canine atrial AP was modified to reproduce measured Ca(2+)-transients of
      control and ATR myocytes. RESULTS: In control, APD to 95% repolarization
      (APD(95)) decreased by 91 ms experimentally and by 88 ms in the model over the 1
      6 Hz range. In ATR myocytes, APD(95) failed to decrease over the 1-6 Hz range.
      Ca(2+)-handling abnormalities in ATR myocytes included slowed upstroke, decreased
      amplitude and strong single-beat post-rest potentiation. Unaltered Ca(2+)
      handling properties included caffeine-releasable Ca(2+)-stores and Ca(2+)
      transient relaxation before and after exposure to the sarcoplasmic reticulum
      Ca(2+)-ATPase (SERCA) inhibitor cyclopiazonic acid (CPA). Including ICR alone in
      the model accounted for loss of APD(50) rate-adaptation; however, KR alone
      reduced APD(95) rate-adaptation by only 19% to 71 ms. When both ICR and Ca(2+)
      handling changes were incorporated, APD(95) rate-adaptation decreased to 6 ms,
      accounting for experimental observations. CONCLUSION: ICR alone does not fully
      account for loss of APD rate-adaptation with atrial remodeling: Ca(2+)-handling
      changes appear to contribute to this clinically significant phenomenon.

PMID- 12062347
TI  - Analysis of altered gene expression during sustained atrial fibrillation in the
      goat.
AB  - OBJECTIVE: Atrial fibrillation (AF) is characterised by electrical, gap
      junctional and structural remodelling. However, the underlying molecular
      mechanisms of these phenomena are largely unknown. To get more insight into
      atrial remodelling at the molecular level we have analysed changes in gene
      expression during sustained AF in the goat. METHODS: The differential display
      technique (DD) was used to identify genes differentially expressed during
      sustained AF (13.9 +/- 5.2 weeks) as compared to sinus rhythm (SR). Dot-blot
      analysis was performed to confirm the altered gene expression and to establish
      the changes in expression after 1, 2, 4, 8 and 16 weeks of AF.
      Immunohistochemistry and western blotting were used to validate the DD approach
      and to further characterise the changed expression of the beta-myosin heavy chain
      gene at the protein level. RESULTS: Of the approximately 125 fragments that
      showed changed expression levels during AF, 34 were cloned and sequenced. Twenty
      one of these represented known genes involved in cardiomyocyte structure,
      metabolism, expression regulation, or differentiation status. The changed
      expression of 70% of the isolated clones could be confirmed by dot-blot analysis.
      In addition, time course analysis revealed different profiles of expression as
      well as transient re-expression of genes, e.g. the gene for hypoxia-inducible
      factor 1 alpha during the first week of AF. During sustained AF the frequency of
      cardiomyocytes expressing beta myosin heavy chain (beta MHC) increased from 21.8
      +/- 2.1 to 47.9 +/- 2.5% (S.E.M.). The overall expression of MHC (alpha+beta)
      appeared to be down-regulated during AF. CONCLUSIONS: AF is accompanied by
      changes in expression of proteins involved in cellular structure, metabolism,
      gene expression regulation and (de-)differentiation. Most alterations in
      expression confirm or support the hypothesis of cardiomyocyte de-differentiation.
      Furthermore, the results suggest a role for ischemic stress in the early response
      of cardiomyocytes to AF, possibly via activation of hypoxia-inducible factor 1
      alpha.

PMID- 12062348
TI  - Effects of inhibiting Na(+)/H(+)-exchange or angiotensin converting enzyme on
      atrial tachycardia-induced remodeling.
AB  - BACKGROUND: Inhibitors of the Na(+)/H(+)-exchanger (NHE1) and of angiotensin
      converting enzyme (ACE) have been shown to reduce short-term (<6 h) tachycardia
      induced atrial electrical remodeling. The role of NHE1 and ACE in longer-term
      electrical remodeling, as might occur with persistent AF, has not been studied.
      METHODS: Dogs were subjected to atrial-tachypacing (400 bpm) for 7 days during
      treatment with 240 mg/day (standard clinical dose) of the NHE1 inhibitor
      cariporide (CariL, n=6), 1000 mg/day cariporide (CariH, n=6), 2 mg/kg/day of the
      ACE inhibitor enalapril (E, n=6), or no-drug controls (n=7). To ensure steady
      state concentrations at the onset of pacing, treatment began 3 days before the
      initiation of atrial tachypacing. Results were compared to those of unpaced dogs
      (n=9). RESULTS: Atrial tachypacing reduced atrial effective refractory period
      (ERP), e.g. at a basic cycle length of 300 ms from 126+/-4 ms (unpaced, mean+/
      S.E.) to 79+/-8 ms (no-drug controls, P<0.001). ERP abbreviation was unchanged by
      CariL (83+/-8 ms), CariH (80+/-7 ms), or E (76+/-5 ms). Atrial tachypacing
      increased mean duration of the longest AF episode in each dog (DAF) from 130+/-80
      s (unpaced) similarly in all groups: 864+/-364 s, no-drug controls; 609+/-376 s,
      CariL; 709+/-353 s, CariH; 645+/-365 s, E (P=NS for differences among groups).
      Sustained AF requiring cardioversion for termination was induced in 0% of unpaced
      dogs vs. 33% of CariL, 33% of CariH, 33% of E, and 43% of control dogs. AF
      inducibility by single extrastimuli increased from 4+/-2% in unpaced dogs to 48+/
      13% (P<0.01) in no-drug control dogs, an effect not changed by CariL (33+/-14%),
      CariH (35+/-17%) or E (48+/-16%). CONCLUSIONS: In contrast to short-term (several
      hour) atrial tachycardia-induced remodeling, remodeling by 7-day tachycardia is
      not affected by NHE1 or ACE inhibition. These results support the notion that
      short-term atrial tachycardia remodeling involves different mechanisms from
      longer-term remodeling, and urges caution in extrapolating results from studies
      of short-term remodeling to effects in longer-term remodeling as often occurs
      clinically.

PMID- 12062349
TI  - Daily oral verapamil before but not after rapid atrial excitation prevents
      electrical remodeling.
AB  - BACKGROUND: Intravenous verapamil has been reported to prevent electrical
      remodeling induced by rapid atrial excitation of several minutes to several
      hours. However, the clinical efficacy of verapamil when taken orally and daily
      remains controversial. PURPOSE: We attempted to demonstrate our hypothesis that
      if verapamil prevents calcium (Ca) overload, its efficacy would be greater when
      taken before, rather than after, the onset of rapid atrial excitation. METHODS:
      In 24 dogs, pacing and recording electrodes were sutured onto the right atrium.
      After a 5-day recovery period, rapid atrial pacing at 400 ppm was started,
      followed 2 days later by oral verapamil (8 mg/kg per day) in eight dogs (After
      group; A). In another eight dogs, oral verapamil administration was begun 1 week
      before the initiation of rapid pacing (Before group; B). In the remaining eight
      dogs, only rapid atrial pacing was started, without oral verapamil (Control
      group; C). We measured the effective refractory period (ERP) and conduction
      velocity (CV), and calculated wavelength (WL) at cycle lengths 200 and 300 ms on
      the day before (P0), and after 2 (P2), 7 (P7), 14(P14) days of rapid pacing.
      RESULTS: In response to rapid atrial pacing, ERP, CV, WL decreased and
      progressively and comparably in A and C (P<0.05 vs. P0). In contrast, in B, these
      parameters did not change significantly and remained greater than those in A and
      C (P<0.05). Moreover, the adaptation of ERP to rate was preserved only in B. The
      duration of atrial fibrillation (AF) was shorter in B than in A and C (P<0.05).
      The inducibility of AF tended to be lower, and the fibrillation cycle length was
      longer in B than in A and C. CONCLUSIONS: Oral verapamil started before but not
      after rapid atrial excitation prevents electrical remodeling. Verapamil may exert
      beneficial effects when it is taken during sinus rhythm, but not after more than
      2 days of atrial tachyarrhythmia.

PMID- 12062350
TI  - Enalapril effects on atrial remodeling and atrial fibrillation in experimental
      congestive heart failure.
AB  - OBJECTIVE: Atrial remodeling contributes to the maintenance of atrial
      fibrillation (AF) in several cardiac disorders. There is evidence that
      angiotensin-converting enzyme (ACE) inhibitors reduce the prevalence of AF in
      patients with congestive heart failure (CHF). There have been no studies
      performed to assess the effects of ACE inhibitors on atrial dimensions and
      emptying function in relationship to vulnerability to AF in the setting of
      experimental CHF. METHODS: CHF was produced in 20 dogs by rapid right ventricular
      pacing during 5 weeks. The dogs were randomized to enalapril (EN) therapy (2
      mg/kg/day, n=10) or to a control group (n=10). Echocardiography was performed at
      baseline and weekly thereafter. At the 5-week electrophysiological study, AF was
      induced by burst pacing and AF duration was measured. RESULTS: Atrial areas
      increased significantly with CHF. Left atrial (LA) fractional area shortening
      (FAS) decreased by 42% (P=0.0001) in controls but by 9% (P=NS) in the EN group
      (P=0.01, EN vs. controls). Similar findings were observed for right atrial (RA)
      changes (P=0.02). Atrial fibrosis was highly correlated with the decrease in LA
      FAS (r=0.85, P<0.01) and was reduced by EN (from 11.2+/-1.6 to 8.3+/-0.7%,
      P=0.008). AF duration was 720+/-461 s for controls and 138+/-83 s for EN
      (P=0.001). LA and RA areas and FAS at 5 weeks correlated with AF duration (P< or
      =0.001 for all). FAS decrease in both atria also correlated with AF duration at
      follow-up (r=0.78 and 0.77 for LA and RA, P< or =0.001 for both). CONCLUSIONS:
      Experimental CHF causes structural and functional abnormalities in both atria,
      which are correlated with AF duration. ACE inhibition attenuates CHF-induced
      atrial fibrosis and remodeling and reduces associated AF promotion. These results
      indicate a role for the renin-angiotensin system in arrhythmogenic atrial
      structural remodeling in CHF.

PMID- 12062351
TI  - Cellular electrophysiologic properties of old canine atria provide a substrate
      for arrhythmogenesis.
AB  - OBJECTIVE: The incidence of atrial fibrillation increases with age. We
      hypothesized that aging-associated changes in the atrial action potential (AP)
      and conduction velocity provide a substrate for abnormal conduction and
      arrhythmogenesis. METHODS: We used microelectrode techniques to record AP from
      the endocardium of the right atrial wall of dogs aged 1-5 (adult) and >8 years
      (old). Conduction velocity was measured between two microelectrodes 3-10 mm
      apart. Histological study was carried out to assess fibrosis. RESULTS: Whereas
      resting potential, AP amplitude and V(max) did not differ with age, the plateau
      was more negative and AP duration was longer in old tissue. The L-type calcium
      current (I(Ca,L)) agonist Bay K8644 (10(-8)-10(-6) mol/l) elevated the plateau
      and shortened APD more in old than in adult, such that AP contour in old atria
      approached that of adult. In contrast, the I(Ca,L) blocker nisoldipine (10(-8)
      10(-5) mol/l) depressed the plateau in adult and had no effect in old. There was
      no difference between the two groups in conduction velocity of normal beats,
      whereas for early premature impulses, reduced conduction velocity and a wider
      time window manifesting slow conduction were detected in old in comparison to
      adult tissue. A twofold increase in the amount of fibrous tissue was detected in
      old atria. CONCLUSIONS: Our data show significant differences in contour of AP in
      adult and old atria. The responses to Bay K8644 and nisoldipine suggest a
      decreased I(Ca,L) in old atrial tissue. The alterations in AP contour and
      increased fibrosis may be responsible for slower conduction of early premature
      beats in old atria. The age-related changes in conduction of premature beats are
      consistent with those observed in patients with paroxysmal atrial fibrillation
      and may contribute to the greater propensity to atrial fibrillation in the aged.

PMID- 12062352
TI  - Endovascular stimulation within the left pulmonary artery to induce slowing of
      heart rate and paroxysmal atrial fibrillation.
AB  - OBJECTIVE: In recent years there have been many reports dealing with basic models
      for sustained atrial fibrillation (AF), however few animal models exist for
      paroxysmal AF which closely simulate that seen clinically. METHODS: In 12 dogs,
      anesthetized with sodium pentobarbital, a right thoracotomy was performed. We
      stabilized a basket electrode catheter within the left pulmonary artery (LPA)
      through a purse string suture in the right ventricle. Electrode catheters were
      sutured to multiple atrial sites including the four pulmonary veins and the right
      and left atrial appendages, along Bachman's bundle and the coronary sinus.
      RESULTS: Continuous pulses of electrical stimulation (20 Hz square wave stimuli,
      each 0.1 ms in duration, voltage range 1-40 V) across adjacent splines of the
      five arms of the basket induced slow heart rates (at lower voltages) and then
      initiated atrial premature depolarizations (APDs), atrial tachycardia (AT) and AF
      (at higher voltages). To avoid possible direct activation of atrial myocardium,
      we also applied a train (50-100 ms duration) of high frequency stimuli (200 Hz)
      coupled to each atrial paced beat so that the train fell within the atrial
      refractory period. Stimulation in the LPA at an average of 14+/-7 V induced heart
      rate slowing, APDs were seen followed by AT/AF at a voltage of 20+/-6 V, P=0.002.
      Stimulation in the LPA resulted in APDs arising from a variety of sites including
      the left pulmonary veins (superior or inferior) and the left atrial appendage.
      After beta-blockade (intravenous esmolol or propranolol, 1 mg/kg) the voltage
      threshold for induction of AF rose from 14+/-7 to 25+/-10 V, P=0.02. Upon the
      addition of intravenous atropine (1-2 mg) the arrhythmic response (AF) to
      stimulation was completely abolished. Atrial pacing threshold was unchanged after
      autonomic blockade. Local application of radiofrequency energy (average
      number=3+/-2) across the metallic splines of the basket catheter in the LPA (70
      80 V for 60 s) caused abolition of both the slowing and the arrhythmic response
      to LPA stimulation. CONCLUSION: These data suggest that stimulation of autonomic
      nerves in the LPA causes slowing of the heart rate followed by paroxysmal
      APD/AT/AF simulating the spontaneously occurring paroxysmal AF syndrome,
      associated with bradycardia, reported in patients.

PMID- 12062353
TI  - Suppression of atrial fibrillation by multisite and septal pacing in a novel
      experimental model.
AB  - OBJECTIVES: To evaluate the preventive efficacy of multisite and septal atrial
      pacing in an experimental model. METHODS: Sterile right atrial pericarditis was
      induced in 12 foxhounds to provide an anatomical substrate for atrial
      fibrillation (AF). As a trigger mechanism, atrial extrasystoles were simulated by
      constant asynchronous pacing at a cycle length of 1000 ms from randomly selected
      right or left atrial electrodes, using a biatrial epicardial multielectrode with
      128 bipoles. Additionally, a transvenous pacing lead was screwed into the
      interatrial septum. Four electrodes located in the high and low right (HRA/LRA)
      and left atrium (HLA/LLA) were selected for preventive multisite stimulation.
      Constant pacing at a cycle length 30 ms below sinus rate was applied from the
      following site(s): HRA, septal, HRA+LRA, HRA+LLA, HRA+LRA+LLA and HRA+LRA+HLA+LLA
      (order randomized). Number and duration of AF episodes were studied during 10 min
      intervals, separated by 5 min pauses, respectively. To validate the model, the
      protocol was repeated 10 min after i.v. bolus administration of D,L-sotalol (1
      mg/kg body weight). RESULTS: The number of AF episodes decreased with increasing
      number of pacing sites, reaching statistical significance compared to HRA
      stimulation for quadruple-site and single-site septal pacing only (P<0.05).
      Single-site septal was as efficient as quadruple-site pacing in suppressing AF.
      The duration of AF episodes was not significantly affected by the pacing
      configuration. D,L-sotalol almost completely suppressed AF irrespective of the
      pacing configuration used. CONCLUSIONS: In this novel experimental model,
      quadruple-site and septal pacing effectively suppress paroxysmal AF.

PMID- 12062354
TI  - The failing human heart.

PMID- 12062355
TI  - Repolarization abnormalities in heart failure.

PMID- 12062356
TI  - Vasopressin antagonists in CHF: ready for clinical trials?

PMID- 12062357
TI  - Application of gene expression profiling to cardiovascular disease.
AB  - The number of cardiovascular publications featuring gene expression profiling
      technologies is growing rapidly. This article introduces four profiling
      techniques; serial analysis of gene expression, differential display, subtractive
      hybridisation and DNA microarrays. Illustrations of their application towards
      cardiovascular research are given and their potential for gene discovery and
      improving our understanding of gene function is discussed.

PMID- 12062358
TI  - Growth hormone, insulin-like growth factor-1 and the aging cardiovascular system.
AB  - There is a large body of evidence that biological aging is related to a series of
      long-term catabolic processes resulting in decreased function and structural
      integrity of several physiological systems, among which is the cardiovascular
      system. These changes in the aging phenotype are correlated with a decline in the
      amplitude of pulsatile growth hormone secretion and the resulting decrease in
      plasma levels of its anabolic mediator, insulin like growth factor-1 (IGF-1). The
      relationship between growth hormone and biological aging is supported by studies
      demonstrating that growth hormone administration to old animals and humans raises
      plasma IGF-1 and results in increases in skeletal muscle and lean body mass, a
      decrease in adiposity, increased immune function, improvements in learning and
      memory, and increases in cardiovascular function. Since growth hormone and IGF-1
      exert potent effects on the heart and vasculature, the relationship between age
      related changes in cardiovascular function and the decline in growth hormone
      levels with age have become of interest. Among the age-related changes in the
      cardiovascular system are decreases in myocyte number, accumulation of fibrosis
      and collagen, decreases in stress-induced cardiac function through deterioration
      of the myocardial conduction system and beta-adrenergic receptor function,
      decreases in exercise capacity, vessel rarefaction, decreased arterial compliance
      and endothelial dysfunction leading to alterations in blood flow. Growth hormone
      has been found to exert potent effects on cardiovascular function in young
      animals and reverses many of the deficits in cardiovascular function in aged
      animals and humans. Nevertheless, it has been difficult to separate the effects
      of growth hormone deficiency from age-related diseases and associated
      pathologies. The development of novel animal models and additional research are
      required in order to elucidate the specific effects of growth hormone deficiency
      and assess its contribution to cardiovascular impairments and biological aging.

PMID- 12062359
TI  - How to evaluate plaque vulnerability in animal models of atherosclerosis?
AB  - Prevention of heart attack and stroke depends on detection of vulnerable plaques
      and development of plaque-stabilizing therapies. In turn, progress in diagnostics
      and treatment is contingent on our understanding of molecular mechanisms of
      plaque vulnerability. Animal models are essential for testing mechanistic
      hypotheses in a controlled manner. Currently, there is no single, golden standard
      animal model of a vulnerable plaque. However, the whole range of experimental
      approaches is readily available. It includes traditional models of
      atherosclerosis combined with new 'vulnerability endpoints', as well as several
      models featuring spontaneous or induced plaque rupture/thrombosis. This review
      summarizes current literature on the animal models of vulnerable atherosclerotic
      plaques.

PMID- 12062360
TI  - Repolarization abnormalities and their arrhythmogenic consequences in porcine
      tachycardia-induced cardiomyopathy.
AB  - OBJECTIVES: Action potential prolongation related to the alteration of several
      membrane currents is constantly reported in heart failure (HF) but reports about
      its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy
      with long QT syndromes, whether prolonged repolarization is associated with
      increased dispersion or linked to bradycardia-dependent ventricular arrhythmias
      in pacing-induced cardiomyopathy. METHODS: QT intervals, action potentials and
      transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed
      rectifier (I(K)) and transient outward (I(to1)) K+ currents were recorded in left
      ventricle from pigs with HF and controls. HF was obtained after 14 days of rapid
      pacing at 250 ms. RESULTS: Repolarization was delayed as indexed by corrected QT
      intervals (13.7% increase, P<0.01) or ARIs (252+/-4 to 340+/-7 ms, P<0.01). ARIs
      were uniformly prolonged with disappearance of the transmural gradient, spatial
      dispersion of repolarization decreased by 50% (P<0.05). I(to1) density was
      reduced in HF from 1.35+/-0.1 to 0.57+/-0.04 pA/pF subepicardially, from 1.05+/
      0.19 to 0.55+/-0.08 pA/pF midmyocardially and from 1.04+/-0.1 to 0.48+/-0.04
      pA/pF subendocardially. I(K) density was significantly decreased in HF pigs vs.
      controls: subepicardially from 0.46+/-0.04 to 0.22+/-0.02 pA/pF; midmyocardially
      from 0.46+/-0.05 to 0.25+/-0.03 pA/pF; and subendocardially from 0.49+/-0.04 to
      0.20+/-0.04 pA/pF following depolarization at +50 mV. Electrocardiogram (ECG)
      monitoring at the time of death did not disclose any polymorphic ventricular
      tachyarrhythmia. CONCLUSION: Despite a profound alteration in K+ currents,
      repolarization is uniformly prolonged in this model with no proclivity to develop
      bradycardia-dependent arrhythmias.

PMID- 12062361
TI  - Neurohormonal antagonism in heart failure; beneficial effects of vasopressin
      V(1a) and V(2) receptor blockade and ACE inhibition.
AB  - OBJECTIVE: To assess the long-term efficacy of vasopressin (AVP) V(1a) and V(2)
      receptor blockade with conivaptan, alone and in combination with angiotensin
      converting enzyme (ACE) inhibition on blood pressure, metabolic and neurohormonal
      parameters, and cardiovascular structure in a rat model of congestive heart
      failure (CHF). METHODS: CHF was induced by left coronary artery ligation. CHF
      rats received conivaptan (1 mg/kg/day), ACE inhibition (captopril, 50 mg/kg/day),
      conivaptan and captopril (Combination) or vehicle for 4 weeks. Blood pressure was
      measured weekly, metabolic caging studies performed at 25 days, and rats killed
      and blood and tissue collected after 4 weeks treatment. RESULTS: Combination
      treatment lowered blood pressure (P<0.01), and conivaptan and Combination caused
      an aquaresis (P<0.01). Combination decreased plasma natriuretic peptide (P<0.05),
      reduced left and right ventricular mass (P<0.01) and lung mass (P<0.05).
      CONCLUSIONS: In CHF, blockade of vasopressin V(1a) and V(2) receptors was
      associated with increased water excretion, and the combination of conivaptan with
      ACE inhibition was the only treatment to reduce blood pressure, natriuretic
      peptide and pulmonary congestion. These results suggest conivaptan may be a
      useful addition to ACE inhibitors in the management of vasoconstriction and fluid
      retention that characterizes CHF.

PMID- 12062362
TI  - Body surface potential mapping in patients with Brugada syndrome: right
      precordial ST segment variations and reverse changes in left precordial leads.
AB  - OBJECTIVE: The aim of this study was to perform quantitative signal analysis of
      high-resolution body surface potential mapping (BSPM) recordings to assess its
      usefulness for the electrocardiographic characterization of patients with Brugada
      syndrome. The diagnostic value of the QRS integral and of the gradient of the ST
      segment have not been elucidated in Brugada syndrome. METHODS: In 27 subjects (16
      with Brugada syndrome and 11 healthy subjects), 120-lead BSPMs were recorded at
      baseline and after pharmacological provocation with intravenous administration of
      ajmaline (1 mg/kg). The recordings were analyzed for two regions outside the
      positions of the standard ECG leads: the right precordial leads (RPL) on the
      second and third intercostal space (high RPL) and the left precordial leads (LPL)
      between the fifth and seventh intercostal space (low LPL). RESULTS: At baseline,
      in high RPL regions, patients with Brugada syndrome showed more positive QRS
      integrals (-5+/-8 vs. -16+/-8 mV ms) and a steeper negative ST segment gradient (
      0.62+/-0.41 vs. -0.29+/-0.40 mV/s) compared to healthy subjects, P<0.001. In
      contrast, in low LPL regions, reduced QRS integrals and positive ST segment
      gradients were observed. These ECG signs were even more pronounced after
      intravenous ajmaline and showed a better discrimination for patients with Brugada
      syndrome than differences in RPL or LPL during baseline, respectively.
      CONCLUSIONS: In the left precordial leads, patients with Brugada syndrome showed
      ECG changes which were reversed in relation to the ECG changes observed in right
      precordial leads. BSPM measurement is a useful tool to improve the understanding
      of the electrocardiographic changes in the Brugada syndrome.

PMID- 12062363
TI  - Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG
      in a patient with long QT syndrome.
AB  - OBJECTIVE: In a 32-year-old woman with marked QT prolongation (QTc=0.61 s) and
      repeated episodes of syncope, we identified a single pertinent base substitution
      (G to A at 1909) in HERG by genetic analysis. This novel missense mutation is
      predicted to cause an amino acid substitution of lysine for glutamic acid at
      position 637 (E637K) in the pore-S6 loop. Therefore, we investigated the role of
      a glutamic acid at the vicinity of the pore in HERG channels by mutating it to a
      lysine. METHODS: We characterized the electrophysiological properties of the
      E637K mutation using a Xenopus oocyte heterologous expression system. RESULTS:
      Injection of the E637K mutant cRNA alone into Xenopus oocytes did not result in
      any expression of detectable currents. Coexpression of wild-type (WT) and E637K
      (E637K/WT) elicited only about 30% of the control peak tail current that was
      expected from expression of WT alone. Kinetic analyses revealed that E637K/WT
      decelerated the rate of channel activation and enhanced steady-state
      inactivation. Furthermore, the reversal potentials at low concentrations of K+
      showed a positive shift in oocytes injected with E637K/WT compared with WT alone.
      CONCLUSIONS: These results indicated that the E637K mutation causes apparent
      dominant negative suppression of WT HERG channel function and suggest that E637
      at the Pore-S6 is a crucial component of the activation and inactivation gate of
      HERG channels.

PMID- 12062364
TI  - Noninvasive assessment of the effects of nicorandil on left ventricular volumes
      and function in reperfused myocardial infarction.
AB  - OBJECTIVE: Nicorandil, a K-ATP channel opener with a nitrate-like effect, is a
      potent vasodilator and has favorable hemodynamic effects in heart failure
      patients. While its cardio-protective properties in the setting of acute ischemia
      are well known, the long-term effects of oral nicorandil therapy on post
      infarction left ventricular (LV) dilatation have not been investigated. METHODS:
      Myocardial infarction (MI) was induced in 30 Sprague-Dawley rats by 1 h of
      coronary artery occlusion followed by reperfusion. After matching for infarction
      size, animals were randomly assigned to nicorandil treatment (3 mg/kg/day) given
      in tap water or no treatment (control group). Treatment was started 2 days after
      MI and continued for 8 weeks. Contrast-enhanced and functional magnetic resonance
      imaging (MRI) were used to determine infarction size, LV volumes, mass, ejection
      fraction, and regional wall thickness. RESULTS: Nicorandil significantly
      decreased end-systolic volumes (0.33+/-0.02 ml; P<0.05) and improved LV ejection
      fraction (37+/-2%; P<0.01) compared to control rats (0.43+/-0.04 ml and 28+/-2%,
      respectively) 8 weeks after MI. During the study period, the increase in LV mass
      (DeltaLVM) was significantly greater in control (0.09+/-0.03 g) than in treated
      animals (0.02+/-0.02 g, P<0.05). Moreover, nicorandil improved systolic wall
      thickening of the rim of infarction (P<0.001) and remote non-infarcted regions
      (P<0.01). CONCLUSION: These results demonstrate that the long-term oral treatment
      with nicorandil started 2 days after MI attenuates left ventricular dilatation
      and improves cardiac function in rats with reperfused MI.

PMID- 12062365
TI  - Cardioprotection by long-term ET(A) receptor blockade and ACE inhibition in rats
      with congestive heart failure: mono- versus combination therapy.
AB  - OBJECTIVES: We investigated the effects of long-term endothelin A (ET(A))
      receptor blockade and ACE inhibition, either alone or in combination, on the
      hemodynamics, neurohormonal activation and cardiac remodeling in rats with
      congestive heart failure (CHF) after extensive myocardial infarction (MI).
      METHODS: Rats were treated with placebo, the ET(A) antagonist LU135252 (30
      mg/kg/d), the ACE inhibitor trandolapril (0.3 mg/kg/d), or a combination of both
      for 11 weeks, starting 7 days after MI. RESULTS: Despite comparable effects on
      left ventricular (LV) systolic pressure among all drug treatments, only combined
      ET(A) and ACE inhibition significantly reduced LV end-diastolic pressure
      (P<0.01), improved LV dP/dt(max) (P<0.01) and normalized sympathetic activation
      (P<0.05) in rats with CHF. The combination therapy was more effective in reducing
      type I and III collagen mRNA levels, MMP-2 zymographic activity and collagen
      accumulation in the surviving LV myocardium. Moreover, the increases in cardiac
      beta-myosin heavy chain and skeletal alpha-actin mRNAs, markers of hypertrophy or
      failure, were attenuated to a greater degree by the combination therapy than
      monotherapy, whereas right ventricular hypertrophy and ANF mRNA upregulation were
      significantly (P<0.01) prevented only by combined ET(A) and ACE inhibition.
      CONCLUSION: Long-term combined ET(A) receptor and ACE inhibition improved cardiac
      failure after extensive MI more effectively than monotherapy. We show additive
      effects on LV fibrosis and fetal gene expression. ET(A) receptor antagonists
      could be a therapeutical option in CHF in addition to an ACE inhibitor.

PMID- 12062366
TI  - Induction of iNOS expression in skeletal muscle by IL-1beta and NFkappaB
      activation: an in vitro and in vivo study.
AB  - OBJECTIVE: The intracellular pathway and the regulation of inducible nitric oxide
      synthase (iNOS) expression in skeletal muscle is incompletely understood. In
      vitro studies, using different cell types, suggest that inflammatory cytokines
      are potential triggers to induce iNOS expression. METHODS: To analyze
      intracellular pathways leading to iNOS induction, rat skeletal myoblasts were
      incubated with inflammatory cytokines and assessed for iNOS expression by Western
      blot and Griess reaction. To confirm the in vitro findings, local cytokine levels
      were determined in skeletal muscle biopsies of patients with chronic heart
      failure (CHF) and correlated with iNOS expression. RESULTS: Nitrite accumulation
      in the myoblast culture supernatant or iNOS protein in the cell pellet was
      significantly increased after incubation with IL-1beta in combination with gamma
      IFN. Priming experiments revealed that gamma-IFN elevated the expression of IL
      1beta receptor mRNA, whereby IL-1beta was able to induce iNOS expression. The
      cytokine-mediated iNOS induction was significantly reduced by blocking ERK1/ERK2
      activation and completely abolished by the inhibition of NFkappaB. In skeletal
      muscle biopsies of CHF patients the local content of IL-1beta was significantly
      increased as compared to healthy controls. Furthermore, a linear correlation
      between IL-1beta content and iNOS expression in the skeletal muscle was detected.
      CONCLUSIONS: These data demonstrate that IL-1beta, together with the priming
      effect of gamma-IFN, induces iNOS expression in skeletal muscle via activation of
      ERK1/ERK2 and NFkappaB.

PMID- 12062367
TI  - Enhanced myocyte contractility and Ca2+ handling in a calcineurin transgenic
      model of heart failure.
AB  - OBJECTIVE: Impaired myocyte Ca2+ handling is a common characteristic of failing
      hearts and increases in calcineurin activity, a Ca2+-sensitive phosphatase, have
      been implicated in heart failure phenotype. Transgenic mice with cardiac-specific
      expression of an active form of calcineurin display depressed function,
      hypertrophy and heart failure. We examined whether defects in cardiomyocyte Ca2+
      handling properties contribute to the impaired cardiac function in calcineurin
      transgenic mice. METHODS: The levels of SR Ca2+ handling proteins, SR Ca2+
      transport function and cardiomyocyte mechanics, as well as Ca2+ kinetics were
      examined in mice overexpressing a constitutively active form of calcineurin.
      RESULTS: Transgenic expression of activated calcineurin catalytic subunit
      resulted in significant protein increases (66%) in SERCA2 and decreases (35%) in
      phospholamban, as well as enhanced (approximately 80%) phospholamban
      phosphorylation. These alterations in the SR Ca2+-transport proteins resulted in
      increased V(max) and Ca2+-affinity of SERCA2. The myofibrillar Mg-ATPase activity
      was also significantly increased at pCa>6.0. The enhanced SR Ca2+ handling and Mg
      ATPase activity reflected significant elevation in myocyte contractile parameters
      (3-fold), Ca2+ transient amplitude (1.5-fold) and the rate of Ca2+ signal decay
      (2-fold). In contrast, in vivo cardiac function assessed by echocardiography,
      indicated severely depressed contractility in calcineurin hearts. The apparent
      disparity in contractile properties between the cellular and multicellular
      preparations may be partially due to tissue remodeling, including interstitial
      fibrosis and a marked reduction (45%), dephosphorylation (81%) and redistribution
      of the gap junctional protein connexin-43, which could compromise intercellular
      communication. CONCLUSION: Despite enhanced SR Ca2+ handling and contractility in
      myocytes, pathological remodeling and defects in intercellular coupling may
      underlie contractile dysfunction of the calcineurin hearts.

PMID- 12062368
TI  - Cardiac function and electrical remodeling of the calcineurin-overexpressed
      transgenic mouse.
AB  - OBJECTIVE: To study the specificity of contractile phenotype and
      electrophysiological remodeling in transgenic (Tg) mice with cardiac directed
      calcineurin (phosphatase 2B) overexpression and evaluate a possible negative role
      of chronically activated calcineurin in beta-adrenergic mediated contractile
      response. METHODS: The patch-clamp technique was used to characterize
      electrophysiological properties of action potentials and inward rectifier
      (I(K1)), and transient outward potassium currents (I(to)). The analysis of the
      contractile performance was carried out on isolated retrograde perfused hearts at
      constant aortic pressure. RESULTS: Tg mice demonstrated a hypercontractile
      phenotype characterized by a profound beta-adrenergic hypo-responsiveness at 2.0
      mM [Ca2+](o). Transgenic cardiomyocytes showed marked action potential
      prolongation (209% in APD(90)) with increased I(to,peak) and I(sus) and decreased
      protein expression level of Kv1.5 and Kv2.1. Lowering [Ca2+](o) to 0.75 mM
      restored the beta-adrenergic response, indicating that the
      calcineurin/calmodulin/adenylyl cyclase (AC) pathway may not be directly
      responsible for the blunted beta-adrenoreceptor mediated inotropism. CONCLUSIONS:
      Calcineurin overexpression leads to development of a hyperdynamic phenotype with
      a cellular profile of increased calcium influx. This type of functional
      hypertrophic remodeling is accompanied by a negative feedback regulation between
      increased calcium handling and beta-adrenergic contractile activation.

PMID- 12062369
TI  - Adrenergic activation of cardiac phospholipase D: role of alpha(1)-adrenoceptor
      subtypes.
AB  - OBJECTIVE: Adrenergic stimulation of the heart leads to activation of the
      phospholipase D signal transduction pathway with formation of the intracellular
      second messengers phosphatidic acid and diacylglycerol, which may play a role in
      the development of myocardial hypertrophy by activating mitogen-activated protein
      kinases and protein kinase C. So far, the adrenergic receptor subtypes mediating
      activation of cardiac phospholipase D are not known. METHODS: We developed an
      assay for determination of phospholipase D activity in the isolated perfused rat
      heart. Utilizing the phospholipase D specific transphosphatidylation reaction the
      stable product phosphatidylethanol (PEtOH) is formed in rat hearts perfused in
      the presence of 1% ethanol. Myocardial PEtOH formation was used as a marker of
      phospholipase D activity and was determined by HPLC and evaporative light
      scattering detection (PEtOH microg/mg myocardial protein). RESULTS: Basal PEtOH
      formation in unstimulated hearts was 0.06+/-0.01 microg/mg. Stimulation of the
      hearts with norepinephrine resulted in a concentration-dependent phospholipase D
      activation with a maximum formation of PEtOH (0.17+/-0.01 microg/mg) at 100
      micromol/l norepinephrine. The norepinephrine-induced increase in PLD activity
      was completely blocked by the alpha(1)-adrenoceptor antagonist prazosin and was
      unaffected by the beta-adrenoceptor antagonist propranolol. Further
      characterisation of alpha(1)-adrenoceptor subtypes with selective alpha(1)
      adrenoceptor antagonists demonstrated a complete inhibition of the norepinephrine
      induced phospholipase D activation by WB 4101 (alpha(1A)-selective: 0.06+/-0.01
      microg/mg) and by BMY 7378 (alpha(1D)-selective: 0.07+/-0.01 microg/mg). In
      contrast, the alpha(1B)-adrenoceptor antagonist chloroethylclonidine had no
      inhibitory effect on norepinephrine-stimulated phospholipase D activity (0.14+/
      0.01 microg/mg). CONCLUSION: Adrenergic activation of the cardiac phospholipase D
      signal transduction pathway is mediated by alpha(1)-adrenoceptors. Here, the
      alpha(1A)-adrenoceptor subtype, but not the alpha(1B)-adrenoceptor are coupled to
      activation of cardiac phospholipase D.

PMID- 12062370
TI  - A proteasome inhibitor confers cardioprotection.
AB  - OBJECTIVE: In several cell types, proteasome inhibitors like carbobenzoxyl
      leucinyl-leucinyl-leucinal (MG132) induce the 72 kDa heat shock protein (Hsp72)
      and exert cell protective effects. However, data in cardiomyocytes are currently
      lacking. METHODS AND RESULTS: We investigated the effects of MG132 in cultured
      neonatal rat cardiomyocytes. MG132 time- and concentration-dependently induced
      Hsp72 and Hsp32 at mRNA and protein levels. Although Hsp60 mRNA was induced,
      Hsp60 protein levels were not altered. MG132 activated p38 MAP kinase already
      after 0.5 h. Hsp mRNA induction started after 2 h of MG132 treatment.
      Subsequently, Hsp72 and Hsp32 protein levels were increased after 4 h. SB202190,
      an inhibitor of p38 MAP kinase, concentration-dependently attenuated MG132
      induced Hsp72-and Hsp32-elevations (by 59% and 41%, respectively, at 1 microM
      SB202190). In contrast, herbimycin A, a known inductor of Hsp72 in
      cardiomyocytes, enhanced the MG132-induced Hsp72 and Hsp32 expression even
      further: additionally applied 2 microM herbimycin A induced Hsp72 and Hsp32 about
      2-fold higher than 1 microM MG132 alone. MG132 (1 microM) decreased the
      hyperthermia- or hydrogen peroxide-induced release of lactate dehydrogenase by
      45% and by 35%, respectively (P<0.05, n=5). MG132 (1 microM) prolonged the
      spontaneous beating time of cardiomyocytes at 46 degrees C from 5+/-2 min
      (control hyperthermia) to 28+/-5 min (P<0.05, n=4). Thus, inhibition of the
      proteasome function by MG132 protects cardiomyocytes against hyperthermic or
      oxidative injury. This protective effect and Hsp induction were abolished by 1
      microM SB202190. CONCLUSION: Proteasome inhibition results in p38 MAP kinase
      dependent induction of Hsp72 and Hsp32 and might be a novel cardioprotective
      modality.

PMID- 12062371
TI  - Developmental changes in the functional characteristics and expression of voltage
      gated K+ channel currents in rat aortic myocytes.
AB  - OBJECTIVE: Active control of the arterial diameter by vascular smooth muscle is
      one of the principle mechanisms by which vessels adapt to a significant rise in
      blood pressure after birth. Although voltage-gated K+ (Kv) channels play an
      important role in the regulation of excitation-contraction coupling in arteries,
      very little is known about postnatal modification of Kv channels. We therefore
      investigated changes in the functional characteristics and expression of Kv
      channels in rat aortic myocytes (RAMs) during early postnatal development.
      METHODS: Kv currents (I(Kv)) were investigated in single smooth muscle cells
      freshly dispersed from neonatal (1-3 days) and adult Wistar rat thoracic aorta
      using the whole-cell patch clamp technique. RESULTS: I(Kv) in neonates had
      significantly faster activation kinetics and was inactivated at more positive
      voltages than I(Kv) in adults (half-inactivation potential -24+/-2 and -40+/-3 mV
      and slope factor 4.2+/-0.4 and 11.1+/-0.5 mV, respectively). No difference in the
      steady state activation was found. I(Kv) in neonates was insensitive to a high
      concentration of tetraethylammonium (TEA, 10 mM) but blocked 4-aminopyridine (4
      AP, IC(50)=0.5+/-0.1 mM), whereas I(Kv) in adult RAMs was almost completely
      abolished by 10 mM TEA and was relatively insensitive to low concentrations of 4
      AP. I(Kv) in both age groups was insensitive to charybdotoxin (300 nM) or alpha
      dendrotoxin (200 nM). Immunoblot analysis showed that the expression of Kv1.2
      alpha-protein decreased and Kv2.1 increased with development. CONCLUSION:
      Significant changes in functional characteristics of the native I(Kv) and the
      expression of particular Kv channel proteins occurred during postnatal vascular
      development. These changes could play an important role in adaptation to
      extrauterine life.

PMID- 12062372
TI  - Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility,
      Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction.
AB  - OBJECTIVE: Although it is generally accepted that endurance training improves
      cardiac function after myocardial infarction the sub-cellular mechanisms are
      uncertain. The present study reports the effects of aerobic endurance training on
      myocardial mass, myocyte dimensions, contractile function, Ca2+ handling, and
      myofilament responsiveness to Ca2+ in cardiomyocytes from healthy and failing rat
      hearts. METHODS: Adult female Sprague-Dawley rats ran on a treadmill 1.5 h/day, 5
      days a week for 8 weeks. Exercise intervals alternated between 8 min at 85-90% of
      V(O(2max)) and 2 min at 50-60%. Training started 4 weeks after ligation of the
      left coronary artery (TR-INF, n=11) or sham operation (TR-SHAM, n=6). Sedentary
      animals (SED-SHAM, n=6; SED-INF, n=13) were controls. RESULTS: After 6 weeks
      V(O(2max)) in TR-INF and TR-SHAM leveled off 65% above sedentary controls. In TR
      SHAM, left and right ventricle weights were approximately 25% higher than in SED
      SHAM, myocytes were approximately 13% longer; width remained unchanged. At
      physiological stimulation frequencies, relative myocyte shortening was markedly
      higher whereas peak systolic [Ca2+] and t(1/2) of Ca2+ transient decay were 10
      20% lower, indicating higher Ca2+ sensitivity in cardiomyocytes from trained
      rats, compared to respective controls. In TR-INF the left and right ventricular
      weights, and myocyte length and width were 15, 23, 12, and 20% less than in SED
      INF. Endurance training significantly increased the myocardial SR Ca2+ pump
      (SERCA-2) and sarcolemmal Na+-Ca2+-exchanger (NCX) protein levels to the extent
      that TR-INF did not differ from SED-SHAM. CONCLUSION: This is the first study to
      show that aerobic endurance training attenuates the ventricular and cellular
      hypertrophy in failing hearts. Furthermore, training consistently restores
      contractile function, intracellular Ca2+ handling, and Ca2+-sensitivity in
      cardiomyocytes from rats with myocardial infarction.

PMID- 12062373
TI  - Increased gene expression of tumor necrosis factor superfamily ligands in
      peripheral blood mononuclear cells during chronic heart failure.
AB  - OBJECTIVE: Inflammation may play a pathogenic role in chronic heart failure
      (CHF). The objective of the study was to characterise the imbalance in the
      cytokine network in CHF. METHODS: cDNA expression arrays were used to analyse the
      gene expression of cytokines and related mediators in peripheral blood
      mononuclear cells (PBMC) from CHF patients (n=8) and healthy controls (n=8). Real
      time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was
      used to determine the gene expression of individual genes in additional 12
      patients and eight controls. RESULTS: From 375 genes, 34 were upregulated and two
      downregulated in CHF patients in the cDNA expression array experiments. Regulated
      genes included chemokines/-receptors, members of the transforming growth factor
      beta superfamily, orphan receptors and in particular several members of the tumor
      necrosis factor (TNF) superfamily. Thus, 4-1BB ligand (L), APRIL, CD27L, CD40L,
      FasL, LIGHT, TRAIL-receptor 4 were upregulated, while TRAIL-receptor 3 was
      downregulated. Real-time quantitative RT-PCR confirmed significantly upregulated
      gene expression of APRIL, LIGHT, FasL and CD27L in CHF patients and showed in
      addition significantly enhanced gene expression of TNFalpha and TRAIL.
      CONCLUSION: The present study demonstrates differential gene expression in PBMC
      of several members of the cytokine network in CHF. In particular, the enhanced
      expression of several ligands in the TNF superfamily may reflect a potential
      pathogenic role of these cytokines in CHF.

PMID- 12062374
TI  - Effect of dietary supplementation with omega-3 fatty acids on progression of
      atherosclerosis in carotid arteries.
AB  - OBJECTIVE: Omega-3 polyunsaturated fatty acids (omega-3 PUFA) from fish oil slow
      atherosclerosis progression in coronary arteries, as we showed in a randomized
      double-blind placebo-controlled clinical trial. Embedded in this trial, the
      present study examined the influence of 2 years of dietary supplementation with
      1.65 g omega-3 PUFA per day on progression of carotid atherosclerosis in 223
      patients with coronary artery disease. METHODS: Coronary angiography, a
      comprehensive clinical examination, and intima-media thickness measurement by B
      mode ultrasound of the carotid arteries (common, internal and bifurcation), were
      performed at the study start and study end. An expert panel visually evaluated
      the global change of carotid atherosclerosis on a semiquantitative scale. A
      second outcome measure was the change of overall mean maximum intima-media
      thickness. RESULTS: One hundred and seventy-one patients completed the study. In
      the global change score, 38% of the patients in the fish oil group and 35% in the
      placebo group showed progression. Global change was not different between
      intervention groups. Mean maximum intima-media thickness increased by 0.07+/-0.13
      mm and 0.05+/-0.11 mm in the fish oil and placebo group, respectively (mean+/
      S.D., P=0.24). No correlation was found between the change in carotid and
      coronary arteries. CONCLUSIONS: In this group of selected patients with
      documented coronary artery disease omega-3 PUFA given for 2 years did not
      demonstrate an effect on slowing progression of atherosclerosis in carotid
      arteries as measured by ultrasound.

PMID- 12062375
TI  - Lipid lowering and the assessment of endothelial function.

PMID- 12062378
TI  - Hydrogen and deuterium in myoglobin as seen by a neutron structure determination
      at 1.5 A resolution.
AB  - From the first days of protein neutron structure determination sperm whale
      myoglobin was an object under investigation [Nature 224 (1969) 143, J. Mol. Biol.
      220 (1991) 381]. Nevertheless myoglobin is still of interest [Proc. Natl. Acad.
      Sci. USA 97 (2000) 3872]. The feasibility of the monochromatic neutron
      diffractometer BIX-3 at the JRR-3M reactor at the JAERI [J. Phys. Chem. Solids 60
      (1999) 1623], to collect high-resolution diffraction data in a relatively short
      time stimulated us to repeat the structural determination of myoglobin. The
      structure of metmyoglobin has been determined up to a resolution of 1.5 A. The
      hydrogen atoms were replaced in part, by deuterium soaking the crystals for more
      than 10 years in D(2)O. A refinement of all atoms has been performed including
      the refinement of individual mean square displacements and occupancies of the
      exchangeable protons in backbone hydrogen bonds. A method is described to show
      clear negative scattering densities of the H atoms. Water molecules within the
      protein and on the molecule surface are shown. The exchangeability of H atoms is
      correlated with structural distribution and flexibility.

PMID- 12062380
TI  - Melting of the solvent structure around a RNA duplex: a molecular dynamics
      simulation study.
AB  - From three 2.4-ns molecular dynamics simulations of the r(CpG)(12) duplex
      conducted at 5, 25 and 37 degrees C, a strong temperature dependence of the
      dynamics of the water molecules and ions located in the first nucleic acid
      coordination shell is observed. At 5 degrees C, the highest residence times of
      bound water molecules exceed 1 ns while, at 37 degrees C, they decrease to 0.5 ns
      in agreement with available NMR data. Similar temperature dependencies are
      observed for the potassium ions bound to the duplex. In this temperature range,
      the structure of the RNA helix remains essentially unchanged. Thus, the observed
      alterations correspond to a 'premelting' of the solvent structure around the
      duplex. It is proposed that, before the nucleic acid structure melts, the entropy
      of the solvent increases to a point where it is no longer compensated by the
      enthalpic contribution of solute-solute and solute-solvent interactions. At this
      stage, the weakest structural elements start to melt. In other terms, the
      experimentally observed melting processes are preceded by a melting of the more
      labile solvent structure.

PMID- 12062379
TI  - Hydrogen bonds from water molecules to aromatic acceptors in very high-resolution
      protein crystal structures.
AB  - Short contacts of water molecules with the pi-faces of aromatic residues were
      studied in a set of 75 very high resolution (<1.1 A) protein X-ray crystal
      structures. For 18 water molecules found at distances to aromatic midpoints <3.5
      A, it was attempted to assign the hydrogen bond configuration (without
      experimental knowledge of the H-atom positions) by inspection of the surrounding.
      For approximately one-quarter of the cases, evidence for an O-H...pi hydrogen
      bond was found, another one-quarter does not form such a hydrogen bond, and for
      the remaining half, no conclusive assignment could be made. The results confirm
      the relatively frequent occurrence of aromatic hydrogen bonding in biomolecular
      hydration, but also underline difficulties in hydrogen bond assignment without
      reliable knowledge of the H-atom positions.

PMID- 12062381
TI  - Roles of hydration water molecules in molecular packing of the killer toxin from
      Pichia farinosa in its crystalline state investigated by cryogenic X-ray
      crystallography.
AB  - The hydration structures around the killer toxin from Pichia farinosa were
      investigated by cryogenic X-ray crystallography. In particular, those
      contributing to the molecular association and the crystal contacts were analyzed
      with respect to the geometry and the networks of hydrogen bonds. The hydration
      water molecules attached on the surface so as to make up the surface shape in the
      contact complementary and mediated the intermolecular interactions through the
      networks of hydrogen bonds. Careful inspection of the contact area led to a
      proposal as to the molecular association mode of the toxin to determine the
      biological function in cells. In addition, the water-associated protein-protein
      interactions were approximated well by a simple theoretical equation on the
      solvation force expected in confined geometry. The present analysis may provide a
      way to analyze the crystal contact and molecular recognition in macromolecules in
      aqueous solution.

PMID- 12062382
TI  - Water mediated Dickerson-Drew-type crystal of DNA dodecamer containing 2'-deoxy-5
      formyluridine.
AB  - To investigate the role of divalent cations in crystal packing, a Dickerson-Drew
      type dodecamer with the sequence d(CGCGAATXCGCG), containing 2'-deoxy-5
      formyluridine at X, was crystallized under several conditions with Ba(2+) ion
      instead of Mg(2+) ion. The crystal structure is isomorphous with the original
      Dickerson-type crystal containing Mg(2+) ion. In the Mg(2+)-free crystals,
      however, a five-membered ring of water molecules occupies the same position as
      the magnesium site found in the Mg(2+)-containing crystals, and connects the two
      duplexes similarly to the hydrated Mg(2+) ion. It has been concluded that the
      five-membered water molecules can take the place of the hydrated magnesium cation
      in crystallization. The 5-formyluracil residues form the canonical Watson-Crick
      pair with the opposite adenine residues.

PMID- 12062383
TI  - Contribution of solvent water to the solution X-ray scattering profile of
      proteins.
AB  - A theoretical framework is presented to analyze how solvent water contributes to
      the X-ray scattering profile of protein solution. Molecular dynamics simulations
      were carried out on pure water and an aqueous solution of myoglobin to determine
      the spatial distribution of water molecules in each of them. Their solution X-ray
      scattering (SXS) profiles were numerically evaluated with obtained atomic
      coordinate data. It is shown that two kinds of contributions from solvent water
      must be considered to predict the SXS profile of a solution accurately. One is
      the excluded solvent scattering originating in exclusion of water molecules from
      the space occupied by solutes. The other is the hydration effect resulting from
      formation of a specific distribution of water around solutes. Explicit
      consideration of only two molecular layers of water is practically enough to
      incorporate the hydration effect. Care should be given to using an approximation
      in which an averaged electron density distribution is assumed for the structure
      factor because it may predict profiles considerably deviating from the correct
      profile at large K.

PMID- 12062384
TI  - Structural basis for the unusual properties of 2',5' nucleic acids and their
      complexes with RNA and DNA.
AB  - To provide insights into the unusual properties of 2',5' nucleic acids (iso
      nucleic acids), that includes their rejection by Nature as information molecules,
      modeling studies have been carried out to examine if they indeed possess the
      stereochemical ability to form helical duplexes and triplexes, just as their
      3',5' linked constitutional isomers. The results show that the formation of
      helical duplexes with 2',5' linkages demands a mandatory displacement of the
      Watson and Crick base pairs from the helical axis, as a direct consequence of the
      lateral shift of the sugar-phosphate backbone from the periphery towards the
      interior of the helix. Thus, both duplexes and triplexes formed with a 2',5'
      sugar-phosphate backbone possess this intrinsic trait, manifested normally only
      in A type duplexes of DNA and RNA. It was found that only a 10-fold symmetric
      parallel triplex with isomorphous T.AT triplets is stereochemically favorable for
      isoDNA with 'extended' nucleotide repeats, unlike the 12-fold symmetric triplex
      favored by DNA. The wider nature of a 12-fold triplex, concomitant with mandatory
      slide requirement for helix formation in isoDNA, demands even larger
      displacement, especially with 'extended' nucleotide structural repeats, thereby
      violating symmetry. However, a symmetric triplex possessing higher twist, can be
      naturally formed for isoDNA with a 'compact' nucleotide repeat. Two nanosecond
      molecular dynamics simulation of a 2',5'-B DNA duplex, formed with an intrinsic
      base pair displacement of -3.3 A, does not seem to favor a total transition to a
      typical A type duplex, although enhanced slide, X-displacement, decrease in
      helical rise and narrowing of the major groove during simulation seem to indicate
      a trend. Modeling of the interaction between the chimeric isoDNA.RNA duplex and
      E. coli RNase H has provided a structural basis for the inhibitory action of the
      enzyme. Interaction of residues Gln 80, Trp 81, Asn 16 and Lys 99, of E. coli
      RNase H with DNA of the DNA.RNA hybrid, are lost when the DNA backbone is
      replaced by isoDNA. Based on modeling and experimental observations, it is argued
      that 2',5' nucleic acids possess restricted conformational flexibility for
      helical polymorphism. The inability of isoDNA to favor the biologically relevant
      B form duplex and the associated topological inadequacies related to nucleic acid
      compaction and interactions with regulatory proteins may be some of the factors
      that might have led to the rejection of 2',5' links.

PMID- 12062385
TI  - Hydrogen and hydration of DNA and RNA oligonucleotides.
AB  - In this paper, hydrogen bonding interaction and hydration in crystal structures
      of both DNA and RNA oligonucleotides are discussed. Their roles in the formation
      and stabilization of oligonucleotides have been covered. Details of the Watson
      Crick base pairs G.C and A.U in DNA and RNA are illustrated. The geometry of the
      wobble (mismatched) G.U base pairs and the cis and almost trans conformations of
      the mismatched U.U base pairs in RNA is described. The difference in hydration of
      the Watson-Crick base pairs G.C, A.U and the wobble G.U in different sequences of
      codon-anticodon interaction in double helical molecules are indicative of the
      effect of hydration. The hydration patterns of the phosphate, the 2'-hydroxyl
      groups, the water bridges linking the phosphate group, N7 (purine) and N4 of Cs
      or O4 of Us in the major groove, the water bridges between the 2'-hydroxyl group
      and N3 (purine) and O2 (pyrimidine) in the minor groove are discussed.

PMID- 12062386
TI  - Treatment of aerosolized cowpox virus infection in mice with aerosolized
      cidofovir.
AB  - The Brighton strain of cowpox virus causes lethal bronchopneumonia when delivered
      as a small-particle (1 microm) aerosol to weanling BALB/c mice. We showed
      previously that this disease can be prevented or cured with one subcutaneous
      injection of cidofovir (HPMPC, Vistide). To determine whether even better results
      could be obtained by delivering the drug directly to the respiratory tract, we
      administered cidofovir by small-particle aqueous aerosol before or after
      aerosolized cowpox infection. In a series of five experiments, aerosol doses of
      0.5-5 mg/kg were always more effective than 25 mg/kg and sometimes more effective
      than 100 mg/kg injected subcutaneously, as measured by changes in body and lung
      weight, lung viral titers, pulmonary pathology and survival. A cyclic analog ((1
      [(S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine) (cHPMPC) was
      less protective. The results suggest that aerosolized cidofovir would be
      effective for prophylaxis or early post-exposure therapy of human smallpox or
      monkeypox virus infection.

PMID- 12062387
TI  - Susceptibility of recent Canadian influenza A and B virus isolates to different
      neuraminidase inhibitors.
AB  - Forty-two influenza A and 23 influenza B isolates collected from untreated
      subjects during the 1999-2000 influenza season in Canada were tested for their
      susceptibility to three neuraminidase inhibitors (zanamivir, oseltamivir
      carboxylate and RWJ-270201 or BCX-1812) using a chemiluminescent neuraminidase
      assay. Influenza B isolates were less susceptible than A viruses to all tested
      drugs. RWJ-270201 was the most potent drug against both influenza A(H3N2) (mean
      IC(50): 0.60 nM) and B (mean IC(50): 0.87 nM) viruses. Oseltamivir carboxylate
      was more active than zanamivir for influenza A(H3N2) isolates (mean IC(50): 0.73
      vs. 2.09 nM) whereas it was less potent against B viruses (mean IC(50): 11.53 vs.
      4.15 nM).

PMID- 12062388
TI  - Small molecule modulators of HIV Rev/Rev response element interaction identified
      by random screening.
AB  - A high throughput scintillation proximity assay with biotinylated human
      immunodeficiency virus (HIV) Rev protein and tritiated Rev response element RNA
      was used to screen over 500,000 small molecules. Several chemical classes of
      inhibitors and two chemical classes of enhancers of binding were identified, with
      the molecular weight range being 400-600. The most common structural motif of
      inhibitor was an acidic moiety at the end of a linear aromatic system. Most of
      these modulators had EC(50) values in the 1-10 microM potency range, with several
      below 1 microM. Several classes displayed structure-activity relationships
      suggesting specific molecular interactions between small molecule and
      macromolecule. Several molecules were confirmed as inhibitors in a gel shift
      assay and by surface plasmon resonance analysis. Furthermore, one inhibitor was
      shown to bind the Rev protein with a binding constant equal to its IC(50) value,
      consistent with the mechanism of inhibition being binding Rev. Thus, small
      molecules can modulate this macromolecular protein-RNA interaction in vitro.
      However, no compound demonstrated HIV antiviral activity in a relevant cell-based
      assay.

PMID- 12062389
TI  - Establishment and use of a cell line expressing HSV-1 thymidine kinase to
      characterize viral thymidine kinase-dependent drug-resistance.
AB  - To understand the mechanisms of antiviral drug resistance and to have a system to
      examine the cytotoxicity of herpes simplex virus type 1 (HSV-1) inhibitors that
      are thymidine kinase (TK)-dependent, we have constructed a plasmid pFTK1 by
      inserting a DNA fragment containing the TK gene of HSV-1 strain F into the
      eukaryotic expression vector pcDNA3.1/His A. TK-deficient 143B cells were
      transfected with this vector and neomycin-resistant cells were selected. Cell
      survival in HAT medium and TK activity of the cell lysates were examined to
      ascertain HSV-1 TK expression. A cell line expressing the viral TK gene, FTK143B
      (FTK), was established and used for characterization of two laboratory-derived TK
      deficient drug-resistant HSV-1 mutants of strain F. The antiviral activities of
      several drugs, mostly nucleoside analogues, were compared in the Vero, 143B and
      FTK cell culture systems. We showed that both mutant viruses lost their
      resistance to acyclovir and to other HSV-1 TK-dependent compounds in FTK cells
      but not in Vero and 143B cells. Significantly increased cytotoxicity of
      ganciclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine was also observed in the FTK
      cells. This HSV-1 TK gene-transfected cell model is a useful tool to rapidly
      determine HSV-1 drug resistance at the viral TK level.

PMID- 12062390
TI  - Liposomal encapsulation enhances antiviral efficacy of SPC3 against human
      immunodeficiency virus type-1 infection in human lymphocytes.
AB  - Because encapsulation of antiviral drugs in liposomes resulted generally in
      improved activity against retroviral replication in vivo, the antiviral effects
      of free-SPC3 and liposome-associated SPC3 were compared in cultured human
      lymphocytes infected with HIV-1. SPC3 was entrapped in various liposomal
      formulations, either different in size (mean diameter of 100 and 250 nm), SPC3
      concentration or cholesterol content. Liposome-associated SPC3 were tested for
      both inhibition of cell-cell fusion and infection with HIV-1 clones. SPC3
      inhibited HIV-1-induced fusion at a micromolar concentration range. When
      associated with liposomes, SPC3 was found to be about 10-fold more potent than
      free SPC3 in inhibiting syncytium formation. Continuous treatment with free SPC3
      also inhibited virus production in a dose-dependent manner, with inhibition of
      HIV infection of C8166 T-cells or human peripheral blood lymphocytes (PBLs) at
      micromolar concentrations. Liposomal entrapment was found to increase the
      antiviral efficacy of SPC3 by more than 10- and 5-fold in C8166 and PBLs,
      respectively. These data suggest that the liposome approach may be used to
      improve SPC3 antiviral efficacy.

PMID- 12062391
TI  - Induction of neutralizing antibodies and cytotoxic T lymphocytes in Balb/c mice
      immunized with virus-like particles presenting a gp120 molecule from a HIV-1
      isolate of clade A.
AB  - We have recently developed a candidate HIV-1 vaccine based on virus-like
      particles (VLPs) expressing a gp120 from an Ugandan HIV-1 isolate of the clade A
      (HIV-VLP(A)s). In vivo immunogenicity experiments were performed in Balb/c mice,
      with an immunization schedule based on a multiple-dose regimen of HIV-VLP(A)s
      without adjuvants, showing a significant induction of both humoral and cellular
      immunity. The Env-specific cellular response was investigated in vitro, scoring
      for both the proliferative response of T helper cells and the cytolytic activity
      of cytotoxic T lymphocytes (CTLs). Furthermore, immune sera showed >50%
      neutralization activity against both the autologous field isolate and the
      heterologous T cell adapted B-clade HIV-1(IIIB) viral strain. This is one of the
      first examples of HIV-1 vaccines based on antigens derived from the A clade,
      which represents >25% of all isolates identified world wide. In particular, the A
      clade is predominant in sub-Saharan countries, where 70% of the global HIV-1
      infections occur, and where vaccination is the only rational strategy for an
      affordable prevention against HIV-1 infection.

PMID- 12062392
TI  - Inhibition of human hepatitis B virus (HBV) by a novel non-nucleosidic compound
      in a transgenic mouse model.
AB  - BAY 41-4109 is a member of a class of heteroaryl-pyrimidines that was recently
      identified as potent inhibitors of human hepatitis B virus (HBV) replication. We
      have investigated the antiviral activity of BAY 41-4109 (methyl (R)-4-(2-chloro-4
      fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl-1,4-dihydro-pyrimidine-5
      carboxylate) in HBV-transgenic mice (Tg [HBV1.3 fsX(-)3'5']). Bay 41-4109 was
      administered per os using different schedules (b.i.d. or t.i.d. for up to 28
      days) and dosages ranging from 3 to 30 mg/kg. The compound reduced viral DNA in
      the liver and in the plasma dose-dependently with efficacy comparable to 3TC. In
      contrast to 3TC-treated mice, we found a reduction of cytoplasmic hepatitis B
      virus core antigen (HBcAg) in liver sections of BAY 41-4109-treated mice, which
      indicated a different mode of action. Pharmacokinetic studies in mice have shown
      rapid absorption, a bioavailability of 30% and dose-proportional plasma
      concentrations. We conclude that BAY 41-4109 is a new anti-HBV drug candidate.

PMID- 12062393
TI  - Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir
      carboxylate has altered properties in vitro and is compromised for infectivity
      and replicative ability in vivo.
AB  - Oseltamivir phosphate (Tamiflu, Ro 64-0796) is the first orally administered
      neuraminidase (NA) inhibitor approved for use in treatment and prevention of
      influenza virus infection in man. Oseltamivir phosphate is the pro-drug of the
      active metabolite oseltamivir carboxylate (Ro 64-0802). Extensive monitoring
      throughout the oseltamivir development programme has identified a very low
      incidence of patients who have carried drug-resistant virus. The predominant
      mutation seen is the substitution of arginine for lysine at position 292 of the
      viral NA. The fitness of clinically isolated influenza virus A/Sydney/5/97 (H3N2)
      carrying this mutation was markedly reduced in animal models of influenza virus
      infection. The infectivity and replicative abilities of R292K mutant virus were
      reduced by at least 2 logs in a mouse model of influenza infection and by 2 and 4
      logs, respectively, in the ferret model. Pathogenicity of R292K influenza virus
      A/Sydney/5/97 was reduced in ferrets as measured by inflammatory and febrile
      responses at least in parallel to the decrease in replicative ability. The data
      indicate that the R292K NA mutation compromises viral fitness such that virus
      carrying this mutation is unlikely to be of significant clinical consequence in
      man.

PMID- 12062394
TI  - Virucidal activity and cytotoxicity of the liposomal formulation of povidone
      iodine.
AB  - Two drug formulations of povidone-iodine (PVP-I)--an aqueous PVP-I solution
      (Betaisodona) and a liposomal PVP-I formulation--were tested for their virucidal
      activity and cytotoxicity in cell culture. As to the virudical activity against
      influenza A virus, herpes simplex virus type 1, adenovirus type 8 and human
      rhinovirus type 14, the liposomal formulation of PVP-I proved to be approximately
      as active as the aqueous one. Half maximum cytotoxic PVP-I concentrations were
      0.01-0.07% for aqueous PVP-I and 0.03-0.27% for the liposomal PVP-I formulation
      (XTT reduction assay EZ4U). The detection of lactate dehydrogenase (LDH) release,
      DNA fragmentation (ELISA) and DNA strand breakage (TUNEL assay) after 24 h
      exposure of human embryonic lung fibroblasts to PVP-I revealed that necrosis
      predominates in cells treated with aqueous 0.08-0.32% PVP-I solutions, whereas
      apoptosis was the predominant type of cell death in cells treated with equivalent
      concentrations of liposomal PVP-I formulation. The favorable virucidal efficiency
      together with the preferred apoptotic route of cell death makes the liposomal PVP
      I formulation a promising candidate for topical use in prevention and treatment
      of infections of the eye and the upper respiratory tract.

PMID- 12062395
TI  - Influenza virus carrying an R292K mutation in the neuraminidase gene is not
      transmitted in ferrets.
AB  - A model of influenza transmission has been established in ferrets in which wild
      type influenza infection in a donor ferret can be transmitted sequentially to
      other ferrets. We have studied the transmission in ferrets of a clinical isolate
      of A/Sydney/5/97 (H3N2) carrying the neuraminidase 292K mutation compared with
      the corresponding wild-type virus from the same subject. Donor ferrets (n=four
      per group) were inoculated intranasally with mutant or wild-type virus and each
      housed with three naive contact ferrets. All donor ferrets inoculated with
      wildtype virus were productively infected and transmitted virus to all 12
      contacts, who in turn had high viral titres in their nasal washes. In contrast,
      only two of the donor ferrets inoculated with mutant virus were productively
      infected. There was little or no evidence that the two infected donor animals
      transmitted mutant virus to their contact animals. This ferret model has
      demonstrated that the mutant influenza virus with lysine at position 292 of the
      neuraminidase is of reduced infectivity and does not transmit under conditions in
      which the wild-type virus with arginine at position 292 readily transmits.

PMID- 12062396
TI  - Treatment of lethal cowpox virus respiratory infections in mice with 2-amino-7
      [(1,3-dihydroxy-2-propoxy)methyl]purine and its orally active diacetate ester
      prodrug.
AB  - The acyclic purine nucleoside analog, 2-amino-7-[(1,3-dihydroxy-2
      propoxy)methyl]purine (S2242) and its orally active diacetate ester prodrug
      (HOE961) were reported to be potent inhibitors of vaccinia virus replication in
      cell culture and in infected mice. These compounds were evaluated further, using
      infections with the related cowpox virus. Against a wild-type (WT) cowpox virus
      strain in mouse C127I cell culture, 50% effective concentrations (EC(50),
      determined by plaque reduction assays) of S2242 and cidofovir (a positive
      control) were 3.5 and 1.0 microM, respectively. EC(50) values obtained against a
      cidofovir-resistant strain of the virus were 33 and 230 microM, respectively.
      Compounds were at least ten-fold less potent against WT virus in Vero cells than
      C127I cells. S2242 and cidofovir were 50% inhibitory to the proliferation of
      uninfected C127I cells at 340 and 180 microM, respectively, but neither compound
      inhibited Vero cell growth at 1000 microM. Mice were lethally infected with
      cowpox virus by intranasal inoculation, followed 24 h later by antiviral
      treatment for 5 consecutive days. Once or twice daily intraperitoneal (i.p.)
      treatments with either S2242 or HOE961 at 100 mg/kg per day resulted in > or = 70
      survival compared with no survivors in the placebo group. Lower doses of these
      compounds (10 and 30 mg/kg per day) were not protective, however. Cidofovir was
      100% protective at 30 mg/kg per day. A 10-day course of treatment gave comparable
      survival results and demonstrated the oral efficacy of HOE961. Treatments with
      S2242 (100 mg/kg per day) and cidofovir (30 mg/kg per day) each reduced lung and
      nasal virus titers by approximately ten-fold, whereas, HOE961 (100 mg/kg per day)
      was less active. Overall, S2242 and HOE961 were found to be effective against
      cowpox virus infections in mice but were less potent than cidofovir. Since,
      HOE961 was orally active, it may have advantages over the other parenterally
      administered compounds for treating orthopoxvirus infections.

PMID- 12062397
TI  - In vitro antiviral efficacy of the ganciclovir complexed with beta-cyclodextrin
      on human cytomegalovirus clinical strains.
AB  - The toxicity of the compounds currently used in the treatment of human
      cytomegalovirus (HCMV) infections in immunocompromised hosts may force the
      treatment to be discontinued. The aim of this study was to improve the antiviral
      activity of ganciclovir (GCV), one the most widely used drug, by complexing it
      with beta-cyclodextrin. Cyclodextrins (cds) have the property to form inclusion
      complexes with a great number of molecules and to enhance bioavailability and
      biological properties of these molecules. In this study, we investigated the in
      vitro antiviral activity of complexed GCV against several strains of HCMV: AD169,
      a reference strain, RCL-1, a laboratory mutant resistant to GCV, and four
      clinical isolates. The complexed GCV was more effective than free GCV against all
      HCMV strains tested. Cds as carriers for antiviral drugs would represent a useful
      adjunct to classical treatment procedures. They may make it possible to
      administer lower doses, thus reducing the toxic side effects of the drugs.

PMID- 12062398
TI  - Evolutionary relationship between the bacterial HPr kinase and the ubiquitous PEP
      carboxykinase: expanding the P-loop nucleotidyl transferase superfamily.
AB  - Similarities between protein three-dimensional structures can reveal evolutionary
      and functional relationships not apparent from sequence comparison alone. Here we
      report such a similarity between the metabolic enzymes histidine phosphocarrier
      protein kinase (HPrK) and phosphoenolpyruvate carboxykinase (PCK), suggesting
      that they are evolutionarily related. Current structure classifications place PCK
      and other P-loop containing nucleotidyl-transferases into different folds. Our
      comparison of both HPrK and PCK to other P-loop containing proteins reveals that
      all share a common structural motif consisting of an alphabeta segment containing
      the P-loop flanked by an additional beta-strand that is adjacent in space, but
      far apart along the sequence. Analysis also shows that HPrK/PCK differ from other
      P-loop containing structures no more than they differ from each other. We thus
      suggest that HPrK and PCK should be classified with other P-loop containing
      proteins, and that all probably share a common ancestor that probably contained a
      simple P-loop motif with different protein segments being added or lost over the
      course of evolution. We used the structure-based sequence alignment containing
      residues specific to HPrK/PCK to identify additional members of this P-loop
      containing family.

PMID- 12062399
TI  - Crystal structure of a clavaminate synthase-Fe(II)-2-oxoglutarate-substrate-NO
      complex: evidence for metal centered rearrangements.
AB  - Clavaminate synthase (CAS), a 2-oxoglutarate (2OG) dependent dioxygenase,
      catalyses three steps in the biosynthesis of clavulanic acid. Crystals of CAS
      complexed with Fe(II), 2OG and deoxyguanidinoproclavaminate were exposed to
      nitric oxide (NO) acting as a dioxygen analogue. Prior to exposure with NO, the
      active site Fe(II) is octahedrally coordinated by a water molecule, the 2-oxo and
      1-carboxylate groups of 2OG, and the side-chains of an aspartyl and two
      histidinyl residues. NO binds to the position previously occupied by the 2OG 1
      carboxylate concomitant with rearrangement of the latter to the position
      previously occupied by the displaced water.

PMID- 12062401
TI  - Sucrose metabolism: Anabaena sucrose-phosphate synthase and sucrose-phosphate
      phosphatase define minimal functional domains shuffled during evolution.
AB  - Based on the functional characterization of sucrose biosynthesis related
      protiens[SBP: sucrose-phosphate synthase (SPS), sucrose-phosphate phosphatase
      (SPP), and sucrose synthase (SuS)] in Anabaena sp. PCC7120 and sequence analysis,
      we have shown that SBP are restricted to cyanobacterium species and plants, and
      that they are multidomain proteins with modular architecture. Anabaena SPS, a
      minimal catalytic SPS unit, defines a glucosyltransferase domain present in all
      SPSs and SuSs. Similarly, Anabaena SPP defines a phosphohydrolase domain
      characteristic of all SPPs and some SPSs. Phylogenetic analysis points towards
      the evolution of modern cyanobacterial and plant SBP from a bidomainal common
      ancestral SPS-like gene.

PMID- 12062400
TI  - Distal regulatory regions restrict the expression of cis-linked genes to the
      tapetal cells.
AB  - The oleosin glycine-rich protein genes Atgrp-6, Atgrp-7, and Atgrp-8 occur in
      clusters in the Arabidopsis genome and are expressed specifically in the tapetum
      cells. The cis-regulatory regions involved in the tissue-specific gene expression
      were investigated by fusing different segments of the gene cluster to the uidA
      reporter gene. Common distal regulatory regions were identified that coordinate
      expression of the sequential genes. At least two of these genes were regulated
      spatially by proximal and distal sequences. The cis-acting elements (122 bp
      upstream of the transcriptional start point) drive the uidA expression to floral
      tissues, whereas distal 5' upstream regions restrict the gene activity to tapetal
      cells.

PMID- 12062402
TI  - Thiolsubtilisin acts as an acetyltransferase in organic solvents.
AB  - The catalytic mechanism of arylamine N-acetyltransferase has been proposed to
      involve Cys-His-Asp as its catalytic triad. Thiolsubtilisin, a chemically
      modified enzyme that has a catalytic triad of Cys-His-Asp at the active site,
      mimics the catalysis of arylamine N-acetyltransferase, serotonin N
      acetyltransferase, histone N-acetyltransferase and amino acid N
      acetyltransferase. Thiolsubtilisin not only can catalyze amino acid
      transacetylation, but is also able to catalyze amine transacetylation. Ethyl
      acetate was used as the acylating reagent to form N-acetyl amino acids and amines
      in organic solvents with moderate yield. Hence, these findings broaden our
      understanding of the structural features required for N-acetyltransferases
      activity as well as provide a structural relationship between cysteine protease
      and other N-acyltransferases.

PMID- 12062403
TI  - Primary sequence determinants responsible for site-selective dephosphorylation of
      the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1.
AB  - Site-selective dephosphorylation of receptor tyrosine kinases contributes to
      receptor regulation. The receptor-like protein tyrosine phosphatase DEP-1 site
      selectively dephosphorylates the PDGF beta-receptor. DEP-1 dephosphorylation of
      original and chimeric phospho-peptides spanning the preferred pY1021 and the less
      preferred pY857 and pY562 sites was analyzed. Double substitutions of basic
      residues at -4 and +3 of pY857 and pY562 peptides improved affinity.
      Substitutions of single amino acids indicated preference for an acidic residue at
      position -1 and a preference against a basic residue at position +3. DEP-1 site
      selective dephosphorylation of PDGF beta-receptor is thus determined by the
      primary sequence surrounding phosphorylation sites and involves interactions with
      residues spanning at least between positions -1 and +3.

PMID- 12062404
TI  - Carbohydrate carriers affect adhesion of H. pylori to immobilized Leb
      oligosaccharide.
AB  - The present study involved comparison of adhesion of Helicobacter pylori KH202 to
      immobilized Le(b)-oligosaccharide carried on different carriers, i.e. Leb
      oligosaccharide conjugated with polyacrylamide, bovine serum albumin, and
      dipalmitoylphosphatidylethanolamine (Le(b)-PAA, Le(b)-BSA, and Le(b)-DPPE). All
      of the Le(b)-oligosaccharide-carrying neoglycoconjugates served as ligands for H.
      pylori. However, H. pylori required 10-fold and 100-fold quantities of Le(b)
      antigen to adhere to Le(b)-PAA and to Le(b)-DPPE in comparison to the quantity of
      Le(b)-antigen needed to adhere to Le(b)-BSA, respectively. H. pylori adhesion to
      Le(b)-PAA and Le(b)-DPPE was clearly inhibited by Le(b)-oligosaccharide, but
      adhesion to Le(b)-BSA was hardly inhibited by the oligosaccharide. Therefore, the
      carbohydrate carrier affects the affinity of H. pylori KH202 toward Le(b)
      antigen, although the bacteria recognize Le(b)-antigen regardless of the
      carbohydrate carrier.

PMID- 12062405
TI  - Amyloid fibrils from the mammalian protein prothymosin alpha.
AB  - Mammalian prothymosin alpha, a small (12 kDa) and extremely acidic protein (pI
      3.5), is a member of the growing family of 'natively' unfolded proteins. We
      demonstrate that at low pH ( approximately 3) and high concentrations,
      prothymosin alpha is capable of forming regular elongated fibrils with flat
      ribbon structure 4-5 nm in height and 12-13 nm in width as judged from scanning
      force and electron microscopy. These aggregates induced a characteristic spectral
      shift of thioflavin T fluorescence and their circular dichroism spectra were
      indicative of significant beta-sheet content, suggesting formation of classical
      amyloid. Our findings indicate that natively unfolded proteins may have a general
      propensity to form amyloid fibrils under conditions inducing partially folded
      conformations.

PMID- 12062407
TI  - Overexpression of sTnC polypeptide in muscle cells is controlled by its rapid
      degradation.
AB  - The check-points that maintain stoichiometric synthesis of muscle proteins were
      examined by misexpression of slow troponin C (sTnC) in mouse C2 myotubes. The
      sTnC mRNA was overexpressed in myotubes by transfecting these cells with a
      plasmid construct containing the constitutive CMV promoter-driven sTnC cDNA. An
      approximately four-fold increase of sTnC mRNA level in the transfected cells was
      observed. However, the increased mRNA level did not produce a corresponding
      increase of the sTnC polypeptide level in transfected cells. Only a modest 1.5
      fold increase of the sTnC polypeptide level in the transfected cells was
      observed. The excess sTnC polypeptide in transfected cells was found in the
      soluble form which was not complexed with other thin filament proteins. The
      difference between the increase of sTnC mRNA and the polypeptide levels in
      transfected cells was not due to inefficient translation of the overexpressed
      sTnC mRNA. Analyses of the stability of the sTnC polypeptide in the thin filament
      and in the unassembled soluble forms showed that the excess soluble sTnC
      polypeptide was degraded more rapidly than the sTnC polypeptide of the thin
      filament. Analyses of the mRNA and polypeptide levels of several thin filament
      complements showed no effect of overexpression of the sTnC mRNA.

PMID- 12062406
TI  - Involvement of fibrinogen specific binding in erythrocyte aggregation.
AB  - Increased fibrinogen concentration and erythrocyte aggregation are significant
      risk factors during various cardiovascular diseases and cerebrovascular
      disorders. Currently, fibrinogen-induced erythrocyte aggregation is thought to be
      caused by a non-specific binding mechanism. However, the published data on
      changes in erythrocyte aggregation during hypertension point to the possible
      existence of other mechanism(s). Therefore, we tested the hypothesis that
      specific binding of fibrinogen is involved in erythrocyte aggregation. It was
      found that Oregon Green 488-labeled human fibrinogen specifically binds rat
      erythrocyte membranes with a Kd of 1.3 microM. Further experiments showed that
      the peptide Arg-Gly-Asp-Ser blocked both fibrinogen-induced aggregation of intact
      erythrocytes and specific binding of fibrinogen to the erythrocyte membranes.
      These results suggest that in addition to non-specific binding, a specific
      binding mechanism is also involved in fibrinogen-induced erythrocyte aggregation.

PMID- 12062408
TI  - A comparative structural and functional analysis of cytochrome cM cytochrome c6
      and plastocyanin from the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Cytochrome cM is a new c-class photosynthetic haem protein whose physiological
      role is still unknown. It has been proposed previously that cytochrome cM can
      replace cytochrome c6 and plastocyanin in transferring electrons between the two
      membrane complexes cytochrome b6-f and photosystem I in organisms growing under
      stress conditions. The experimental evidence herein provided allows us to discard
      such a hypothesis. We report a procedure to overexpress cytochrome cM from the
      cyanobacterium Synechocystis sp. PCC 6803 in Escherichia coli cells in mg
      quantities. This has allowed us to perform a comparative laser flash-induced
      kinetic analysis of photosystem I reduction by the three metalloproteins from
      Synechocystis. The bimolecular rate constant for the overall reaction is up to
      100 times lower with cytochrome cM than with cytochrome c6 or plastocyanin. In
      addition, the redox potential value and surface electrostatic potential
      distribution of cytochrome cM are quite different from those of cytochrome c6 and
      plastocyanin. These findings strongly indicate that cytochrome cM cannot be
      recognised by and interact with the same redox partners as the other two
      metalloproteins.

PMID- 12062409
TI  - Placement of 19F into the center of GB1: effects on structure and stability.
AB  - A structural and thermodynamic characterization of 5F-Trp-substituted
      immunoglobulin binding domain B1 of streptococcal protein G (GB1) was carried out
      by nuclear magnetic resonance and circular dichroism spectroscopy. A single
      fluorine reporter atom was positioned at the center of the three-dimensional
      structure, uniquely poised to be exploited for studying interior properties of
      this protein. We demonstrate that the introduction of 5F-Trp does not affect the
      global and local architecture of GB1 and has no influence on the thermodynamic
      stability. The favorable properties of the fluorinated GB1 render this molecule a
      desirable model system for the development of spectroscopic methodology and
      theoretical calculations.

PMID- 12062410
TI  - WARP is a new member of the von Willebrand factor A-domain superfamily of
      extracellular matrix proteins.
AB  - We report a new member of the von Willebrand factor A-domain protein superfamily,
      WARP (for von Willebrand factor A-domain-related protein). The full-length mouse
      WARP cDNA is 2.3 kb in size and predicts a protein of 415 amino acids which
      contains a signal sequence, a VA-like domain, two fibronectin type III-like
      repeats, and a short proline- and arginine-rich segment. WARP mRNA was expressed
      predominantly in chondrocytes and in vitro expression experiments in transfected
      293 cells indicated that WARP is a secreted glycoprotein that forms disulphide
      bonded oligomers. We conclude that WARP is a new member of the von Willebrand
      factor A-domain (VA-domain) superfamily of extracellular matrix proteins which
      may play a role in cartilage structure and function.

PMID- 12062411
TI  - Novel cDNAs encoding salivary proteins from the malaria vector Anopheles gambiae.
AB  - Several genes encoding salivary components of the mosquito Anopheles gambiae were
      identified using a selective trapping approach. Among these, five corresponded to
      genes expressed specifically in female glands and their role may possibly be
      linked to blood-feeding. Our collection included a fourth member of the D7
      protein family and two polypeptides that showed weak similarity to anti
      coagulants from distantly related species. Moreover, we identified two additional
      members of a novel group of proteins that we named glandins. The isolation of
      tissue-specific genes represents a first step toward a deeper molecular analysis
      of mosquito salivary secretions.

PMID- 12062412
TI  - Enhanced activation of bound plasminogen on Staphylococcus aureus by
      staphylokinase.
AB  - Activation of plasminogen (plg) to plasmin by the staphylococcal activator,
      staphylokinase (SAK), is effectively regulated by the circulating inhibitor,
      alpha2-antiplasmin (alpha2AP). Here it is demonstrated that intact Staphylococcus
      aureus cells and solubilized staphylococcal cell wall proteins not only protected
      SAK-promoted plg activation against the inhibitory effect of alpha2AP but also
      enhanced the activation. The findings suggest that the surface-associated plg
      activation by SAK may have an important physiological function in helping
      staphylococci in tissue dissemination. Amino acid sequencing of tryptic peptides
      originating from the 59-, 56- and 43-kDa proteins, isolated as putative plg
      binding proteins, identified them as staphylococcal inosine 5'-monophosphate
      dehydrogenase, alpha-enolase, and ribonucleotide reductase subunit 2,
      respectively.

PMID- 12062413
TI  - Cold stress decreases the capacity for respiratory NADH oxidation in potato
      leaves.
AB  - Cold stress effects on the expression of genes for respiratory chain enzymes were
      investigated in potato (Solanum tuberosum L., cv. Desiree) leaves. The nda1 and
      ndb1 genes, homologues to genes encoding the non-proton-pumping respiratory chain
      NADH dehydrogenases of Escherichia coli and yeast, were compared to genes
      encoding catalytic subunits of the proton-pumping NADH dehydrogenase (complex I).
      Using a real-time PCR system, we demonstrate a specific and gradual decrease of
      the NDA1 transcript after exposing the plants to 5 degrees C. After 6 days of
      cold treatment the NDA1 transcript abundance is 10% of the original level. This
      decrease is accompanied by specific decreases of immunodetected NDA protein and
      internal rotenone-insensitive NADH oxidation in mitochondria isolated from cold
      treated plants. The alternative oxidase is not cold-induced neither at the
      protein nor at the activity level. The results are discussed in relation to the
      recent finding that the nda1 gene expression is completely light-dependent.

PMID- 12062414
TI  - Phytanic acid, but not pristanic acid, mediates the positive effects of phytol
      derivatives on brown adipocyte differentiation.
AB  - The phytol derivatives phytanic acid and pristanic acid may activate nuclear
      hormone receptors and influence gene expression and cell differentiation.
      Phytanic acid induces brown adipocyte differentiation. It was determined that
      brown fat and brown adipocytes are sites of high gene expression of phytanoyl-CoA
      hydroxylase, the enzyme required for initiation of peroxisomal alpha-oxidation of
      phytanic acid. However, the effects of phytanic acid were not mediated by its
      alpha-oxidation product pristanic acid, which did not promote brown adipocyte
      differentiation or stimulate transcription of the uncoupling protein-1 gene.
      Moreover, acute cold exposure of mice caused a dramatic mobilization of the
      phytanic acid stores in brown adipose tissue thus suggesting that a high local
      exposure to phytanic acid in brown fat may contribute to signalling adaptive
      changes in the tissue in response to thermogenic activation.

PMID- 12062415
TI  - Expression of hetN during heterocyst differentiation and its inhibition of hetR
      up-regulation in the cyanobacterium Anabaena sp. PCC 7120.
AB  - The hetN gene plays an important role in heterocyst differentiation and pattern
      formation. An immunoblotting study showed that the hetN gene in Anabaena sp. PCC
      7120 was expressed in vegetative cells grown with combined nitrogen. After a
      switch to a medium without combined nitrogen, hetN expression first declined and
      was then followed by a rapid increase in its product, HetN, which was only
      present in mature heterocysts. HetN is located on both thylakoid membranes and
      plasma membranes as determined by immunoblotting using purified membranes.
      Overexpression of hetN completely prevented hetR up-regulation under nitrogen
      deprivation conditions, suggesting that its role in pattern control may depend on
      its inhibition of hetR expression.

PMID- 12062416
TI  - Tumor necrosis factor alpha stimulates taurine uptake and transporter gene
      expression in human intestinal Caco-2 cells.
AB  - The effect of cytokines on the taurine uptake by human intestinal epithelial Caco
      2 cells was investigated. Among the various cytokines tested, tumor necrosis
      factor alpha (TNF-alpha) markedly increased the taurine uptake by Caco-2 cells,
      resulting in an increase in the intracellular taurine level. TNF-alpha did not
      induce up-regulation of the taurine uptake in hepatic HepG2, renal human embryo
      kidney 293, and macrophage-like THP-1 cells. The uptake of glycine, L-leucine,
      and L-glutamic acid by Caco-2 cells was not affected by TNF-alpha. A kinetic
      analysis of the taurine uptake by TNF-alpha-treated Caco-2 cells suggests that
      this up-regulation was associated with both an increase in the amount of the
      taurine transporter (TAUT) and an increase in its affinity. TNF-alpha-treated
      cells showed a higher mRNA level of the TAUT than did the control cells.

PMID- 12062417
TI  - Aerobic and anaerobic NAD+ metabolism in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae the nicotinic acid moiety of NAD+ can be synthesized
      from tryptophan using the kynurenine pathway or incorporated directly using
      nicotinate phosphoribosyl transferase (NPT1). We have identified the genes that
      encode the enzymes of the kynurenine pathway and for BNA5 (YLR231c) and BNA6
      (YFR047c) confirmed that they encode kynureninase and quinolinate phosphoribosyl
      transferase respectively. We show that deletion of genes encoding kynurenine
      pathway enzymes are co-lethal with the Deltanpt1, demonstrating that no other
      pathway for the synthesis of nicotinic acid exists in S. cerevisiae. Also, we
      show that under anaerobic conditions S. cerevisiae is a nicotinic acid auxotroph.

PMID- 12062418
TI  - Yeast Npi3/Bro1 is involved in ubiquitin-dependent control of permease
      trafficking.
AB  - The membrane traffic and stability of the general amino acid permease Gap1 of
      Saccharomyces cerevisiae are under nitrogen control. Addition of a preferential
      nitrogen source such as ammonium to cells growing on a poor nitrogen source
      induces internalization of the permease and its subsequent degradation in the
      vacuole. This down-regulation requires ubiquitination of Gap1 through a process
      involving ubiquitin ligase Npi1/Rsp5, ubiquitin hydrolase Npi2/Doa4, and Bul1/2,
      two Npi1/Rsp5 interacting proteins. Here we report that yet another protein,
      Npi3, is involved in the regulation of Gap1 trafficking. We show that Npi3 is
      required for NH4+-induced down-regulation of Gap1, and particularly for efficient
      ubiquitination of the permease. Npi3 plays a pleiotropic role in permease down
      regulation, since it is also involved in ubiquitination and stress-induced down
      regulation of the uracil permease Fur4 and in glucose-induced degradation of
      hexose transporters Hxt6/7. We further provide evidence that Npi3 is required for
      direct vacuolar sorting of neosynthesized Gap1 permease as it occurs in npr1
      mutant cells. NPI3 is identical to BRO1, a gene encoding a protein of unknown
      biochemical function and recently proposed to be involved in protein turnover.
      Npi3/Bro1 homologues include fungal proteins required for proteolytic cleavage of
      zinc finger proteins and the mouse Aip1 protein involved in apoptosis. We propose
      that proteins of the Npi3/Bro1 family, including homologues from higher species,
      may play a conserved role in ubiquitin-dependent control of membrane protein
      trafficking.

PMID- 12062419
TI  - The biosynthetic pathway for lipoic acid is present in plastids and mitochondria
      in Arabidopsis thaliana.
AB  - In eukaryotes, the biosynthetic pathway for lipoic acid is present in
      mitochondria. However, it has been hypothesized that, in plants, the biosynthetic
      pathway is present in plastids in addition to mitochondria. In this study,
      Arabidopsis thaliana LIP1p cDNA for a plastidial form of lipoic acid synthase has
      been identified. We show that it encodes a lipoic acid synthase by demonstrating
      its ability to complement an Escherichia coli mutant lacking lipoic acid synthase
      activity. We also show that LIP1p is targeted to chloroplasts. These findings
      suggest that the biosynthetic pathway for lipoic acid is present not only in
      mitochondria but also in plastids.

PMID- 12062420
TI  - A novel positive tetracycline-dependent transactivator (rtTA) variant with
      reduced background activity and enhanced activation potential.
AB  - The tetracycline-controlled transcription system has become one of the most
      potent systems for experimental manipulations of transcription levels in vivo.
      Here we report on rtTA variants, which were generated by combining the existing
      positively regulated Tet repressor domains of rtTA and rtTA-M2 with a modified
      and multimerized minimal transactivation domain from VP16 (L-domain). A
      transactivator with multimerized L-domains shows drastically reduced background
      activity and enhanced transcriptional activation on different tetracycline
      responsive promoters. The new rtTA variants require higher doses of doxycycline
      and display a more linear dose-response curve than the original rtTA or rtTA-M2
      proteins.

PMID- 12062421
TI  - cDNA macroarray analysis of gene expression in synoviocytes stimulated with
      TNFalpha.
AB  - Gene expression of synoviocytes stimulated with tumor necrosis factor-alpha
      (TNFalpha) was studied by macroarray analysis to elucidate the cellular response
      and identify new biological functions of known and unknown genes. 10035 cDNA
      clones were used to make cDNA macroarrays of representative genes. Synoviocytes
      expressed large amounts of fibronectin and collagen mRNA. Statistical analysis of
      the macroarray data revealed 26 genes, including six new genes, which underwent
      significant alteration of gene expression in response to TNFalpha stimulation.
      These findings suggest that the synoviocyte response to TNFalpha stimulation
      forms the basis of development of various aspects of the pathophysiology of
      rheumatoid arthritis.

PMID- 12062422
TI  - Molecular and structural analyses of a novel temperature stress-induced lipocalin
      from wheat and Arabidopsis.
AB  - Two cDNAs corresponding to a novel lipocalin were identified from wheat and
      Arabidopsis. The two cDNAs designated Tatil for Triticum aestivum L. temperature
      induced lipocalin and Attil for Arabidopsis thaliana temperature-induced
      lipocalin encode polypeptides of 190 and 186 amino acids respectively. Structure
      analyses indicated the presence of the three structurally conserved regions that
      characterize lipocalins. Sequence analyses revealed that this novel class of
      plant lipocalin shares homology with three evolutionarily related lipocalins: the
      mammalian apolipoprotein D (ApoD), the bacterial lipocalin and the insect
      Lazarillo. The comparison of the putative tertiary structures of both the human
      ApoD and the wheat TaTIL suggest that the two proteins differ in membrane
      attachment and ligand interaction. Northern analyses demonstrated that Tatil and
      Attil transcripts are upregulated during cold acclimation and heat-shock
      treatment. The putative functions of this novel class of plant lipocalins during
      temperature stresses are discussed.

PMID- 12062423
TI  - Nuclear Apaf-1 and cytochrome c redistribution following stress-induced
      apoptosis.
AB  - Apoptotic protease activating factor-1 (Apaf-1) and cytochrome c are cofactors
      critical for inducing caspase-9 activation following stress-induced apoptosis.
      One consequence of caspase-9 activation is nuclear-cytoplasmic barrier
      disassembly, which is required for nuclear caspase-3 translocation. In the
      nucleus, caspase-3 triggers proteolysis of the caspase-activated DNA nuclease
      (CAD) inhibitor, causing CAD induction and subsequent DNA degradation. Here we
      demonstrate that apoptotic cells show perinuclear cytochrome c aggregation, which
      may be critical for nuclear redistribution of cytochrome c and Apaf-1. We thus
      indicate that the nuclear redistribution of these cofactors concurs with the
      previously reported caspase-9-induced nuclear disassembly, and may represent an
      early apoptotic hallmark.

PMID- 12062424
TI  - Heteronuclear NMR studies of human serum apolipoprotein A-I. Part I. Secondary
      structure in lipid-mimetic solution.
AB  - The apolipoprotein A-I (apoA-I) solution structure in the presence of sodium
      dodecyl sulfate (SDS) was determined by combination of chemical shift index and
      torsion angle likelihood obtained from shift and sequence similarity methods.
      ApoA-I in lipid-mimetic solution is composed of alpha-helices (residues 8-32, 45
      64, 67-77, 82-86, 90-97, 100-118, 122-140, 146-162, 167-205, 210-216 and 221
      239), with 2-5 residue irregular segments between helical repeats, and the
      irregular segment 78-81 within helical repeat 2. ApoA-I is a monomer in the SDS
      complex and no evidence of interhelical interactions is found. Comparison of the
      apoA-I and apoA-I(1-186) [Okon et al., FEBS Lett. 487 (2001) 390-396] solution
      structures revealed that apoA-I undergoes a conformational change around Pro121.

PMID- 12062425
TI  - A metacaspase of Trypanosoma brucei causes loss of respiration competence and
      clonal death in the yeast Saccharomyces cerevisiae.
AB  - Metacaspases constitute a new group of cysteine proteases homologous to caspases.
      Heterologous expression of Trypanosoma brucei metacaspase TbMCA4 in the budding
      yeast Saccharomyces cerevisiae resulted in growth inhibition, mitochondrial
      dysfunction and clonal death. The metacaspase orthologue of yeast, ScMCA1
      (YOR197w), exhibited genetic interaction with WWM1 (YFL010c), which encodes a
      small WW domain protein. WWM1 overexpression resulted in growth arrest and clonal
      death, which was suppressed by concomitant overexpression of ScMCA1. GFP-fusion
      reporters of WWM1, ScMCA1 and TbMCA4 localized to the nucleus. Taken together, we
      suggest that metacaspases may play a role in nuclear function controlling
      cellular proliferation coupled to mitochondrial biogenesis.

PMID- 12062426
TI  - A mutant P53 can activate apoptosis through a mechanism distinct from those
      induced by wild type P53.
AB  - A common mutation in P53 protein occurs at amino acid residue 281 in the DNA
      binding domain (P53(gly(281))), which results in loss of transcriptional
      regulation of P53 target genes and has been reported to gain pro-oncogenic
      functions. In the present study, we investigated the activity of P53(gly(281)) in
      P53-null PC3 human prostate cancer cells and found that the P53(gly(281)) induced
      apoptosis as efficiently as the wild-type P53 (wtP53). However, in contrast to
      wtP53-induced apoptosis, the P53(gly(281))-induced apoptosis was insensitive to
      overexpression of bcl-2. Thus, our findings indicate that while a mutation in the
      DNA binding domain of p53 may result in a more oncogenic form of the protein, it
      may also paradoxically result in the 'gain' of a new, alternative pathway for
      apoptosis.

PMID- 12062427
TI  - Zinc is required for structural stability of the C-terminus of archaeal
      translation initiation factor aIF2beta.
AB  - aIF2beta is an archaeal homolog of eukaryotic translation factor eIF2beta
      necessary for translation initiation and involved in recognition of the
      initiation codon. In the present study, we demonstrate for the first time zinc
      binding to the C2-C2 zinc finger at the C-terminus of aIF2beta. Nuclear magnetic
      resonance backbone assignments were also determined and the secondary structural
      elements identified.

PMID- 12062428
TI  - Evidence that the putative alpha-glucosidase of Thermotoga maritima MSB8 is a pNP
      alpha-D-glucuronopyranoside hydrolyzing alpha-glucuronidase.
AB  - The gene (agu) encoding p-nitrophenyl alpha-D-glucuronopyranoside (pNP-GUA)
      hydrolyzing alpha-glucuronidase of the hyperthermophilic bacterium Thermotoga
      maritima was cloned and expressed in Escherichia coli. The recombinant enzyme was
      purified and characterized. The gene previously designated as putative alpha
      glucosidase was found to code for a protein that had no alpha-glucosidase
      activity. It showed a rare activity profile with its ability to hydrolyze pNP
      GUA, an activity not known in the alpha-glucuronidases from microbial sources.
      This is the first report on the occurrence of an alpha-glucuronidase which
      belongs to the family 4 of glycosyl hydrolases.

PMID- 12062429
TI  - The dystrophin gene is alternatively spliced throughout its coding sequence.
AB  - We have analysed splicing patterns in the human dystrophin gene region encoding
      the rod and cysteine-rich domains in normal skeletal muscle, brain and heart
      tissues. Sixteen novel alternative transcripts were identified, the majority of
      them being present in all three tissues. Tissue-specific variants were also
      identified, suggesting a functional role of transcriptional diversity. Transcript
      analysis in dystrophinopathic autoptic and bioptic specimens revealed that pre
      mRNAs secondary structure formation and relative strength of exon/exon
      association play little or no role in directing alternative splicing events. This
      analysis also showed that independent deletion events leading to the loss of the
      same exons may be associated with transcriptional variability.

PMID- 12062430
TI  - Identification of casein kinase Ialpha interacting protein partners.
AB  - Casein kinase Ialpha (CKIalpha) belongs to a family of serine/threonine protein
      kinases involved in membrane trafficking, RNA processing, mitotic spindle
      formation and cell cycle progression. In this report, we identified several
      CKIalpha interacting proteins including RCC1, high mobility group proteins 1 and
      2 (HMG1, HMG2), Erf, centaurin-alpha1, synaptotagmin IX and CPI-17 that were
      isolated from brain as CKIalpha co-purifying proteins. Actin, importin-alpha(1),
      importin-beta, PP2Ac, centaurin-alpha1, and HMG1 were identified by affinity
      chromatography using a peptide column comprising residues 214-233 of CKIalpha. We
      have previously shown that centaurin-alpha1 represents a CKIalpha partner both in
      vitro and in vivo. The nuclear protein regulator of chromosome condensation 1
      (RCC1) is a guanosine nucleotide exchange factor for Ran which is involved in
      nuclear transport and mitotic spindle formation. Here we show that CKIalpha and
      RCC1 interact in brain and in cultured cells. However, the interaction does not
      involve residues 217-233 of CKIalpha which are proposed from X-ray structures to
      represent an anchoring site for CKI partners. Formation of the RCC1/CKIalpha
      complex is consistent with the association of the kinase with mitotic spindles.
      In conclusion, we have identified a number of novel CKIalpha protein partners and
      their relations to CKI are discussed.

PMID- 12062431
TI  - Inter-subunit cross-linking of methylamine dehydrogenase by cyclopropylamine
      requires residue alphaPhe55.
AB  - Cyclopropylamine is a mechanism-based inhibitor of the quinoprotein methylamine
      dehydrogenase (MADH) from Paracoccus denitrificans. The resulting inactivation is
      accompanied by the formation of a covalent cross-link between the alpha and beta
      subunits of MADH. The results of site-directed mutagenesis studies indicate that
      Phe55 on the alpha subunit is required for this process. No cross-linking is seen
      with alphaF55A or alphaF55I MADH mutants. In contrast, with alphaF55E MADH cross
      linking of subunits is observed. These results suggest a novel mechanistic role
      for a phenylalanine residue and the possible importance of protein dynamics in
      this enzyme mechanism.

PMID- 12062432
TI  - Enhancement of transglutaminase activity by NMR identification of its flexible
      residues affecting the active site.
AB  - Incorporation of inter- or intramolecular covalent cross-links into food proteins
      with microbial transglutaminase (MTG) improves the physical and textural
      properties of many food proteins, such as tofu, boiled fish paste, and sausage.
      By using nuclear magnetic resonance, we have shown that the residues exhibiting
      relatively high flexibility in MTG are localized in the N-terminal region;
      however, the N-terminal region influences the microenvironment of the active
      site. These results suggest that the N-terminal region is not of primary
      importance for the global fold, but influences the substrate binding. Therefore,
      in order to increase the transglutaminase activity, the N-terminal residues were
      chosen as candidates for site-directed replacement and deletion. We obtained
      several mutants with higher activity, del1-2, del1-3, and S2R. We propose a
      strategy for enzyme engineering targeted toward flexible regions involved in the
      enzymatic activity. In addition, we also briefly describe how the number of
      glutamine residues in a substrate protein can be increased by mixing more than
      two kinds of TGases with different substrate specificities.

PMID- 12062434
TI  - Two distinct classes of FixJ binding sites defined by in vitro selection.
AB  - The phosphorylated FixJ transcriptional activator is key to nitrogen fixation in
      Sinorhizobium meliloti, switching both the nifA and fixK genes on. Previously no
      consensus picture emerged concerning the nature of FixJ binding sites. Here we
      used in vitro DNA selection in order to systematically characterise FixJ binding
      sequences. This led to the definition of two classes of sites. Class I sites
      share the CTAAGTAGTTTCCC sequence found in the fixK promoter, whereas class II
      sites are defined by a GTAMGTAG consensus octamer. Our results indicate that FixJ
      approximately P binds DNA following two distinct binding modes.

PMID- 12062435
TI  - A divergent archaeal member of the alkaline phosphatase binuclear metalloenzyme
      superfamily has phosphoglycerate mutase activity.
AB  - The hyperthermophilic archaeon Methanococcus jannaschii uses several non
      canonical enzymes to catalyze conserved reactions in glycolysis and
      gluconeogenesis. A highly diverged gene from that organism has been proposed to
      function as a phosphoglycerate mutase. Like the canonical cofactor-independent
      phosphoglycerate mutase and other members of the binuclear metalloenzyme
      superfamily, this M. jannaschii protein has conserved nucleophilic serine and
      metal-binding residues. Yet the substrate-binding residues are not conserved. We
      show that the genes at M. jannaschii loci MJ0010 and MJ1612 encode thermostable
      enzymes with phosphoglycerate mutase activity. Phylogenetic analyses suggest that
      this gene family arose before the divergence of the archaeal lineage.

PMID- 12062433
TI  - Helicobacter pylori in North and South America before Columbus.
AB  - We present a molecular epidemiologic study, based on an analysis of vacA, cagA
      and cag right end junction genotypes from 1042 Helicobacter pylori isolates,
      suggesting that H. pylori was present in the New World before Columbus. Eight
      Native Colombian and Alaskan strains possessed novel vacA and/or cagA gene
      structures and were more closely related to East Asian than to non-Asian H.
      pylori. Some Native Alaskan strains appear to have originated in Central Asia and
      to have arrived after strains found in South America suggesting that H. pylori
      crossed the Bering Strait from Asia to the New World at different times.

PMID- 12062437
TI  - PKC regulation of the human equilibrative nucleoside transporter, hENT1.
AB  - Regulation of nucleoside transporters is poorly understood. We show that acute
      stimulation of protein kinase C (PKC) causes a rapid increase in S-(4
      nitrobenzyl)-6-thioinosine-sensitive (human equilibrative nucleoside transporter
      1, hENT1) nucleoside uptake, in human cultured cells, which is not due to
      increased metabolism and which can be blocked by PKC inhibitors. Use of isoform
      specific inhibitors indicates that PKC delta and/or epsilon (but not alpha, beta
      or gamma) are responsible for the acute effects. Down-regulation of PKC decreases
      hENT1-dependent uridine uptake. These are the first data to show rapid PKC
      delta/epsilon-dependent stimulation of hENT1 transport by a mechanism that may
      involve activation of transporters at the membrane possibly by post-translational
      modification of the protein.

PMID- 12062436
TI  - A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for
      activation by both mutations and its natural agonist.
AB  - The wide spectrum of naturally occurring mutations able to activate the
      thyrotropin (TSH) receptor provides a useful tool to approach the structure of
      the active state(s) of the glycoprotein hormone receptors. Here we show that the
      side-chain of the highly conserved N7.49 (Asn 674) in TM7 is mandatory for
      activation of the TSH receptor, not only by TSH, but also by a panel of eight
      natural and two artificial activating mutations. Basal activity levels of the
      mutants were significantly decreased by suppression of the side-chain of N7.49
      (N7.49A double mutants). In addition, comparative effects of the N7.49A
      substitution on the ten mutants demonstrate that basal activity and agonist- or
      mutation-stimulated activity might involve different structural changes.

PMID- 12062438
TI  - Role of calmodulin in the modulation of the MAPK signalling pathway and the
      transactivation of epidermal growth factor receptor mediated by PKC.
AB  - We have recently shown that calmodulin (CaM) regulates the trafficking of
      epidermal growth factor receptor (EGFR) as well as the mitogen-activated protein
      kinase (MAPK) signalling pathway. However, the overall regulation of the MAPK
      pathway is achieved through a complex interplay of other several upstream
      effectors including G-proteins, EGF, EGFR, protein kinase C (PKC),
      phosphatidylinositol-3-kinase and CaM. In order to understand the role of CaM in
      the PKC-mediated transactivation of EGFR we have analysed the effect of a CaM
      antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, on the 12-O
      tetradecanoylphorbol-13-acetate-mediated activation of EGFR and the subsequent
      MAPK activation. The results show that CaM interferes with MAPK activation and
      the transactivation of EGFR mediated by PKC.

PMID- 12062439
TI  - A cell-free protein synthesis system as an investigational tool for the
      translation stop processes.
AB  - Using Escherichia coli cell-free protein synthesis system and aminoacylated amber
      suppressor tRNA, we successfully inserted an unnatural amino acid S-(2
      nitrobenzyl)cysteine into human erythropoietin. Three different types of
      translation stop suppression were observed and each of the three types was easily
      discerned with SDS-PAGE. Optimal conditions were established for correct stop and
      programmed suppressions. Since this system differentiates proteins produced by
      misreading of codons from those produced by programmed suppression, we conclude
      that this cell-free translation system that we describe in this paper will be of
      a great use for future investigations on translation stop processes.

PMID- 12062440
TI  - The role of protein glycosylation in the control of cellular N-sialyltransferase
      activity.
AB  - Protein glycosylation, which is a key post-translational event, is catalysed by
      the glycosyltransferase family of enzymes. There is an increasing body of
      evidence to suggest that these enzymes may themselves be glycosylated, possibly
      as an autocatalytic event. Using a novel in vitro system, we have investigated
      the role of enzyme glycosylation in sialyltransferase catalytic activity. The
      enzyme activity is glycosylation dependent, with the penultimate galactose
      residue on complex N-linked oligosaccharides playing a pivotal role. These
      results serve to underline the complexity of the glycosylation process.

PMID- 12062441
TI  - Opening of ligand-gated cation channel families by calpain inhibitors.
AB  - The class of Ca2+-permeable cation channels is composed of large families with
      six transmembrane segments including transient receptor potential, vanilloid
      receptor (VR), polycystin, epithelial calcium channels and melastatin (MLS).
      However, most of them are functionally silent and unexpressed in mammalian cells.
      An investigation of associated proteins made us believe that the blockade of
      calpain opens the silent channels. Using 1 microM of blockers in whole cellular
      patch pipette fill we measured currents of Chinese hamster ovary cells
      transfected by VR-like 1 and 2, polycystin-2, or a MLS-like new member (MLS3S).
      Significant conductance of every clone with a characteristic rectification by
      blockers was demonstrated. The permeability of Ca2+ to them is similar to that
      reported. Western blot suggested that blockers did not affect the assembly of the
      protein but enabled its cleavage. Therefore, investigation of these families with
      the blockers may boost our knowledge of electrophysiologic function.

PMID- 12062442
TI  - Selenoprotein W is a glutathione-dependent antioxidant in vivo.
AB  - The function of selenoprotein W (Se-W) was investigated by cloning the
      corresponding cDNA from mouse brain and expressing it in CHO cells and H1299
      human lung cancer cells. Overexpression of Se-W markedly reduced the sensitivity
      of both cell lines to H2O2 cytotoxicity. The intracellular peroxide concentration
      of the transfected cells was lower than that of the parental cells in the absence
      or presence of extracellular H2O2. The resistance to oxidative stress conferred
      by Se-W was dependent on glutathione. Expression of Se-W mutants in which
      selenocysteine-13 or cysteine-37 was replaced by serine did not confer resistance
      to H2O2, implicating these residues in the antioxidant activity of Se-W in vivo.

PMID- 12062443
TI  - Interaction with substrate sensitises caspase-3 to inactivation by hydrogen
      peroxide.
AB  - Caspases have an active site cysteine whose oxidation blocks catalytic activity.
      Caspase activity, measured in lysates of apoptotic cells, was inhibited by H2O2
      with an IC50 of 7 microM. Recombinant caspase-3 was directly inhibited by H2O2,
      with an estimated second-order rate constant of 750 M-1 s-1. These values were
      determined when H2O2 was added while the caspases were cleaving a peptide
      substrate. There was a 40-fold decrease in sensitivity to inactivation if the
      substrate was absent at the time of H2O2 addition. These results rationalise
      conflicting reports of the sensitivity of caspase-3 to H2O2, and identify a novel
      mechanism for sensitising a thiol enzyme to oxidative inactivation.

PMID- 12062445
TI  - Methionine oxidation inhibits fibrillation of human alpha-synuclein in vitro.
AB  - We examined the effect of methionine oxidation of human recombinant alpha
      synuclein on its structural properties and propensity to fibrillate. Both
      oxidized and non-oxidized alpha-synucleins were natively unfolded under
      conditions of neutral pH, with the oxidized protein being slightly more
      disordered. Both proteins adopted identical partially folded conformations under
      conditions of acidic pH. The fibrillation of alpha-synuclein at neutral pH was
      completely inhibited by methionine oxidation. This inhibitory effect was
      eliminated at low pH. The addition of oxidized alpha-synuclein to the unoxidized
      form led to a substantial inhibition of alpha-synuclein fibrillation.

PMID- 12062444
TI  - Melanophilin directly links Rab27a and myosin Va through its distinct coiled-coil
      regions.
AB  - Rab GTPases regulate the membrane transport pathways by recruiting their specific
      effector proteins. Melanophilin, a putative Rab effector, has recently been
      identified as a gene that is mutated in leaden mice, in which peripheral
      localization of melanosomes is impaired in melanocytes. Genetic studies suggest
      that three coat-color mutation genes, dilute (MyoVa(d)), ashen (Rab27a(ash)), and
      leaden (Mlph(ln)), act in the same or overlapping pathways. Here we have cloned
      and characterized a human melanophilin homolog, which belongs to the
      rabphilin3/granuphilin-like Rab effector family. Cosedimentation assays using
      recombinant proteins reveal that melanophilin directly binds to Rab27a and myosin
      Va through its N-terminal and its first C-terminal coiled-coil region,
      respectively. Moreover, we show that Rab27a, melanophilin, and myosin Va form a
      ternary complex in the human melanocyte cell line HMV-II. These findings suggest
      that melanophilin has a role in bridging Rab27a on melanosomes and myosin Va on
      actin filaments during melanosome transport. We also propose that the Rab-binding
      region conserved in a novel rabphilin3/granuphilin-like Rab effector family
      constitutes an alpha-helix-based coiled-coil structure.

PMID- 12062446
TI  - Metabolic control analysis of anaerobic glycolysis in human hibernating
      myocardium replaces traditional concepts of flux control.
AB  - Myocardial hibernation represents an adaptation to sustained ischemia to maintain
      tissue vitality during severe supply-demand imbalance which is characterized by
      an increased glucose uptake. To elucidate this adaptive protective mechanism, the
      regulation of anaerobic glycolysis was investigated using human biopsies. In
      hibernating myocardium showing an increase in anaerobic glycolytic flux
      metabolizing exogenous glucose, the adjustment of flux through this pathway was
      analyzed by flux:metabolite co-responses. By this means, a previously unknown
      pattern of regulation using multisite modulation was found which largely differs
      from traditional concepts of metabolic control of the Embden-Meyerhof pathway in
      normal and diseased myocardium.

PMID- 12062447
TI  - Involvement of TIRAP/MAL in signaling for the activation of interferon regulatory
      factor 3 by lipopolysaccharide.
AB  - Infections of bacteria and viruses induce host defense reactions known as innate
      responses that include the production of cytokines and chemokines. The production
      of type I interferon (IFN) is known to be induced by viral double-stranded (ds)
      RNA or bacterial lipopolysaccharide (LPS). Although important functions for the
      transcription factors NF-kappaB and interferon regulatory factor-3 (IRF-3) are
      indicated, the molecular signals leading to the activation of IFN genes have yet
      to be elucidated. We provide several lines of evidence that LPS and dsRNA trigger
      distinct intracellular signals upstream. Notably, our investigation revealed a
      critical function for TIRAP/MAL, a signaling adapter for Toll-like receptor (TLR)
      4, in LPS-induced but not dsRNA-induced activation of IRF-3. These results
      highlight cross-talk between TLR-mediated and virus/dsRNA-induced signals
      resulting in activation of the IFN system.

PMID- 12062448
TI  - Evidence for glucose-6-phosphate transport in rat liver microsomes.
AB  - The existence of glucose-6-phosphate transport across the liver microsomal
      membrane is still controversial. In this paper, we show that S3483, a chlorogenic
      acid derivative known to inhibit glucose-6-phosphatase in intact microsomes,
      caused the intravesicular accumulation of glucose-6-phosphate when the latter was
      produced by glucose-6-phosphatase from glucose and carbamoyl-phosphate. S3483
      also inhibited the conversion of glucose-6-phosphate to 6-phosphogluconate
      occurring inside microsomes in the presence of electron acceptors (NADP or
      metyrapone). These data indicate that liver microsomal membranes contain a
      reversible glucose-6-phosphate transporter, which furnishes substrate not only to
      glucose-6-phosphatase, but also to hexose-6-phosphate dehydrogenase.

PMID- 12062449
TI  - Endothelial Rho signaling is required for monocyte transendothelial migration.
AB  - Bacterial toxins affecting Rho activity in microvascular endothelial cells were
      employed to elucidate whether endothelial Rho participates in regulating the
      migration of monocytes across monolayers of cultured endothelial cells.
      Inactivation of Rho by the Clostridium C3 exoenzyme resulted in an increased
      adhesion of peripheral blood monocytes to the endothelium and a decreased rate of
      transendothelial monocyte migration. Cytotoxic necrotizing factor 1-mediated
      activation of endothelial Rho also reduced the rate of monocyte transmigration,
      but did not affect monocyte-endothelium adhesion. Thus, efficient leukocyte
      extravasation requires Rho signaling not only within the migrating leukocytes but
      also within the endothelial lining of the vessel wall.

PMID- 12062450
TI  - Identification of residues important for NAD+ binding by the Thermotoga maritima
      alpha-glucosidase AglA, a member of glycoside hydrolase family 4.
AB  - The NAD+-requiring enzymes of glycoside hydrolase family 4 (GHF4) contain a
      region with a conserved Gly-XXX-Gly-Ser (GXGS) motif near their N-termini that is
      reminiscent of the fingerprint region of the Rossmann fold, a conserved
      structural motif of classical nicotinamide nucleotide-binding proteins. The
      function of this putative NAD+-binding motif in the alpha-glucosidase AglA of
      Thermotoga maritima was probed by directed mutagenesis. The K(d) for NAD+ of the
      AglA mutants G10A, G12A and S13A was increased by about 300-, 5-, and 9-fold,
      respectively, while their K(m) for p-nitrophenyl-alpha-glucopyranoside was not
      seriously affected. The results indicate that the GXGS motif is indeed important
      for NAD+ binding by the glycosidases of GHF4.

PMID- 12062451
TI  - Molecular cloning and characterization of the human p19(INK4d) gene promoter.
AB  - p19(INK4d), a member of the INK4 family of cyclin-dependent kinase (CDK)
      inhibitors, negatively regulates the cyclin D-CDK4/6 complexes, which promote
      G1/S transition by phosphorylating the retinoblastoma tumor-suppressor gene
      product. To investigate the mechanism of transcriptional regulation of the
      p19(INK4d) gene, we characterized the 5'-flanking region of the human p19(INK4d)
      gene. The cap-site hunting method revealed that the transcription starts at -16
      nucleotide (nt) upstream of the initiation codon. The 5'-flanking region of the
      human p19(INK4d) gene was ligated to a luciferase reporter gene and possessed
      functional promoter activity. Luciferase assay with a series of truncated 5'
      flanking regions indicated that the region from -81 to -2 nt could drive the
      transcription of the p19(INK4d) gene. Several Sp1 and activating protein 2
      binding sites are located within the region from -81 to -2 nt. Mutation of the
      second Sp1 binding site from -33 to -25 nt decreased the promoter activity.
      Collectively, it was demonstrated that the human p19(INK4d) gene is under the
      control of TATA-less promoter and the Sp1 binding site is involved in the
      transcription.

PMID- 12062452
TI  - Latent TGF-beta binding protein-3 (LTBP-3) requires binding to TGF-beta for
      secretion.
AB  - Latent transforming growth factor-beta (TGF-beta) binding protein (LTBP)-1, which
      is easily secreted, has been shown to enhance the secretion of TGF-beta. Here we
      show that another member of the LTBP family, LTBP-3, is not secreted by several
      cell types, but secretion occurs after coexpression with TGF-beta. The secretion
      of LTBP-3 requires complexing of LTBP-3 with Cys33 of the TGF-beta propeptide.

PMID- 12062453
TI  - Cathepsin D is specifically inhibited by deoxyribonucleic acids.
AB  - A cathepsin D (CD) inhibitor was searched using mouse embryonic fibroblasts
      deficient for CD. Synthetic DNA fragments specifically inhibited CD activity in a
      dose-dependent manner, but not the activities of other serine or cysteine
      proteinases. Cathepsin E activity was also inhibited by DNA fragments when
      hemoglobin was used as a substrate. CD inhibition by DNA fragments appeared to be
      electrostatic in nature and dependent on Tm values. Moreover, CD activity was
      partly inhibited by exogenously ingested DNA fragments, suggesting that DNA
      fragments with high Tm values are potent inhibitors of CD in vitro and partly in
      vivo.

PMID- 12062454
TI  - Preferential integration of human immunodeficiency virus type 1 into genes,
      cytogenetic R bands and GC-rich DNA regions: insight from the human genome
      sequence.

PMID- 12062456
TI  - A screening trial of amantadine as a medication for cocaine dependence.
AB  - This screening trial evaluated whether amantadine hydrochloride (100 mg bid)
      demonstrated sufficient clinical efficacy compared to placebo to recommend
      development as a pharmacotherapy for cocaine dependence. Participants were
      randomized to amantadine (n=34) or placebo (n=35) conditions in a 16-week,
      placebo-controlled, double blind trial with three times per week group
      counseling. Amantadine-treated participants were retained significantly longer
      than placebo. Based on results of a joint probability index for urine drug
      testing results (i.e. the proportion of cocaine-metabolite free urine samples
      divided by the number of participants assigned to the condition), participants
      assigned to amantadine were found to be significantly more likely to be cocaine
      abstinent on the last day of 8-weeks of treatment than participants assigned to
      placebo. Results at the end of 16 weeks of treatment were similar. Standard
      measures of urine drug testing consistently favored the amantadine condition over
      placebo, although not at levels of statistical significance. There was no
      statistical significance infrequency or severity of reported adverse events by
      treatment condition. Participants assigned to amantadine exhibited greater
      reductions in global staff ratings of cocaine dependence severity from baseline
      to termination compared with placebo. There were no significant differences in
      frequency or severity of reported adverse events by treatment condition. These
      results provide moderate support for further study of amantadine for the
      treatment of cocaine dependence.

PMID- 12062457
TI  - Self-administration of heroin produces alterations in the expression of inducible
      nitric oxide synthase.
AB  - Nitric oxide plays a critical role in the immune response, and our studies have
      shown that heroin induces a reduction in the expression of iNOS, the enzyme
      responsible for nitric oxide production. The present study evaluated the effect
      of heroin self-administration on iNOS expression using a three-group design.
      Group one (self-administration) was trained to press a lever for i.v.
      administration of heroin. Group two (yoked heroin) received a simultaneous
      equivalent infusion of heroin determined by the responses of a 'partner' animal
      in the first group. A third group (yoked saline) also was yoked to the first
      group, but received i.v. injections of saline. Immediately following the last
      session, all rats received an injection of lipopolysaccharide (LPS) to induce
      iNOS expression. About 6 h after the injection of LPS, iNOS mRNA and protein
      expression were determined in spleen, lung, and liver. Additionally, the
      accumulation of plasma nitrite/nitrate, the more stable end products of nitric
      oxide degradation were measured. Although there was not a consistent difference
      between the self-administering and yoked-heroin animals, the results show that
      rats will self-administer a sufficient amount of heroin to induce a pronounced,
      widespread reduction in the expression of iNOS.

PMID- 12062458
TI  - Cognitive bias for alcohol-related information in inferential processes.
AB  - Cognitive biases for alcohol-related stimuli have been shown to play a major role
      in the maintenance of alcohol addiction, thus making their study an issue of
      paramount importance. Such cognitive biases have been traditionally investigated
      with low-level, non-inferential processes, such as the Stroop task [for a review
      see Psychol. Bull. 120 (1996) 3]. However, explanations for these effects [for
      example, the current-concerns explanation; Motivation, Attention, and Volition
      (1987) 336] posit that biases should mediate cognitive processes more generally,
      not limited to a single aspect of cognition. In the present study, we addressed
      this issue within an experimental paradigm extensively used for the study of
      learning and inference. Participants who were heavy users of alcohol were
      impaired in the task when the stimuli were alcohol-related but not impaired when
      the stimuli were neutral. By contrast, participants who were light users of
      alcohol performed equivalently on the alcohol-related and neutral versions of the
      learning task.

PMID- 12062459
TI  - Are drunk-driving offenders referred for screening accurately reporting their
      drug use?
AB  - Several studies report that a substantial percentage of offenders arrested for
      impaired driving test positive for drugs of abuse besides alcohol. Current
      guidelines recommend screening offenders for both alcohol and other drug use, yet
      little is known about the accuracy of self-reports of drug use in this
      population. We compared drug abuse and dependence DSM-III-R diagnoses from an
      initial, court-ordered screening evaluation of 583 female and 495 male convicted
      drunk-driving offenders with diagnoses obtained via a voluntary, non-coerced
      interview 5 years later. At initial screening, fewer than 6% of offenders were
      diagnosed with drug abuse or dependence. Among offenders who did not receive an
      initial drug diagnosis, 28% subsequently reported having experienced drug use
      problems consistent with a retrospective diagnosis of drug abuse or dependence by
      the age at which they were screened. Half of those with a retrospective diagnosis
      of drug dependence reported their initial screening responses were "very
      accurate". We conclude that, although many drunk-driving offenders undergoing
      screening have diagnosable drug problems, a high proportion under-report their
      drug use. We suggest that certain modifications to screening procedures, such as
      urine drug screening, reducing barriers to treatment, and training counselors in
      motivational interviewing techniques, may increase accurate identification of
      drug use problems in this population.

PMID- 12062460
TI  - Parental substance use disorder and the risk of adolescent drug abuse: an event
      history analysis.
AB  - A common observation in the research literature is that children of drug
      dependent parents are at significantly heightened risk of adolescent drug use,
      abuse, and dependence. Recent research indicates that several psychological and
      interpersonal factors may affect the association between parents' psychoactive
      substance use disorder (PSUD) and drug use risks among adolescents, yet studies
      have failed to examine explicitly whether these factors moderate the association
      between PSUD and adolescent substance abuse. This paper explores these potential
      relationships using longitudinal data from a study that has followed three
      cohorts of adolescents and their families over a 7-year period. The cohorts are
      defined by parental diagnoses of PSUD, affective disorders, or no diagnosable
      disorder. The results indicate that PSUD is positively associated with adolescent
      drug abuse, yet this association is attenuated by strong family cohesion.
      Affective disorders among parents are associated with a higher risk of alcohol,
      but not drug, abuse. The associations are stronger in the presence of lower
      stress and higher self-esteem. PSUD is also associated more strongly with
      offspring drug and alcohol abuse when levels of use are lower. Hence, some
      unobserved mechanism that may involve physiological sensitivities to drugs and
      alcohol appears to put children of parents with drug problems at particular risk
      of drug and alcohol abuse. Limitations of the data and analysis are discussed.

PMID- 12062461
TI  - Impaired inhibitory control of behavior in chronic cocaine users.
AB  - This study examined the ability to inhibit and execute behavioral responses in
      adult cocaine users and in an aged-matched sample with no history of cocaine use.
      Subjects (n=22) were identified as cocaine users by testing positive for the
      presence of cocaine or benzoylecgonine in urine-analysis and by self-reported
      cocaine use. Control subjects (n=22) tested negative in urine-analysis and
      reported no past cocaine use. Response inhibition and response execution were
      measured by a stop-signal paradigm using a choice reaction time task that engaged
      subjects in responding to go-signals when stop-signals occasionally informed them
      to inhibit the response. Cocaine users displayed significantly poorer ability to
      inhibit their behavioral responses than did controls. Specifically, cocaine users
      required more time to inhibit responses to stop-signals and displayed a lower
      probability of inhibiting their responses. Cocaine users did not differ from
      controls in their ability to execute responses as measured by their speed and
      accuracy of responses to go-signals. These findings are important because they
      identify a specific deficit involving behavioral inhibition that could contribute
      to cocaine abuse, and explain its association with other disorders of self
      regulation, such as ADHD.

PMID- 12062462
TI  - Deaths by unintentional illicit drug overdose in Italy, 1984-2000.
AB  - AIM: To determine whether there has been an increase in deaths by overdose in
      Italy, as elsewhere in the Western world, over the past fifteen years. METHOD:
      This study's conclusions are based on analysis of official data on overdose
      deaths attributed to illicit drug addiction and abuse (ICD-9 codes 304 and 305)
      from 1984 to 2000, drawn from two archives of drug abuse information: the
      Direzione Centrale per i Servizi Antidroga (DADE) of the Italian Ministry of the
      Interior (1984-2000), and the Health Statistics held at the Italian Central
      Statistics Institute (ISTAT) (1984-1997). Mortality rates have been calculated
      for both genders in the following age groups: 15-24, 25-34, and 35-44 years.
      RESULTS: Official data indicate that there has been a steady increase in the
      number of deaths by overdose in Italy over recent 15 years. This trend has
      affected both genders, but is more evident among males. Over the whole period
      females had consistently lower overdose rates than males. In both genders the age
      group 35-44 was subject to the highest mortality rate increase over the study
      period, however, the highest overdose rates for both males and females were
      observed in the 25-34 age group. Consistently higher rates were witnessed in the
      northern regions of Italy with an overall increase across all latitudes. However,
      the greatest increase over the study period occurred in the South. In 5190 cases
      evaluated by the Italian Forensic Toxicology Group, 95.9% of deaths were
      attributed to heroin, but in about half of these, mixtures of three or more
      substances (heroin, benzodiazepines, cannabinoids, cocaine, methadone) were found
      in the deceased at doses that were likely to have contributed to death.
      CONCLUSIONS: The increase observed in the rates of death by overdose is likely to
      be a reflection of increased use of illicit drugs in the general population.
      Reporting practice by forensic pathologists might explain the extent of
      attribution of cause of death to heroin. Drop-out from addiction treatment is a
      commonly observed antecedent of fatal opioid overdose, therefore, caution is
      required when establishing treatment protocol for patients. Interventions that
      aim specifically at improving patient compliance with medical and psychiatric
      therapies should be favoured.

PMID- 12062463
TI  - A controlled trial of methadone treatment combined with directly observed
      isoniazid for tuberculosis prevention in injection drug users.
AB  - Substance abuse is associated with high risk for tuberculosis (TB) and poor
      adherence to medication regimens. This study compared completion rates for
      isoniazid (INH) preventive therapy for injection drug users (IDUs) randomly
      assigned to methadone treatment combined with directly observed preventive
      treatment (DOPT) versus those assigned to routine TB clinic referral without
      methadone treatment. One hundred and eleven opioid-dependent patients with latent
      TB were assigned to one of three 6-month treatment conditions: standard methadone
      treatment including substance abuse counseling combined with daily INH DOPT
      (n=37); minimal methadone treatment without counseling, also combined with daily
      INH DOPT (n=35); or routine care referral to TB clinic for monthly INH supplies
      without DOPT and without methadone treatment (n=39). INH completion rates were
      77.1% for minimal methadone and 59.5% for standard methadone, as compared with
      only 13.5% for routine care (P<0.0001). Mean duration of INH treatment retention
      was 5.7, 5.0 and 1.6 months, respectively (P<0.0001). TB incidence at 4-year
      follow-up was 0 of 54 subjects who completed preventive therapy versus 2 of 57
      who failed to complete. One of these two had been assigned to routine care, and
      the other to minimal methadone. In conclusion, INH retention time and completion
      rates were significantly improved by methadone treatment combined with observed
      INH, whether or not substance abuse counseling was provided. The results of this
      study indicate that methadone treatment offers clear public health benefits when
      it is used to deliver preventive medical services.

PMID- 12062464
TI  - Relationship between LAAM-methadone preference and treatment outcomes.
AB  - Studies of relative LAAM-methadone preference have indicated that a significant
      proportion of patients prefer levo-alpha-acetylmethadol (LAAM). The present study
      was designed to determine whether this preference is associated with better
      treatment outcomes. Sixty-two stable methadone patients participated in a
      randomised crossover clinical trial. They received LAAM (alternate days) and
      methadone (daily) for 3 months each, followed by a further 6-month period during
      which they were free to choose between the drugs. LAAM maintenance was associated
      with a lower rate of heroin use than methadone maintenance based on analysis of
      morphine concentration in hair and equivalent health outcomes. The majority of
      subjects showed a preference for LAAM (n=27, 69.2%) rather than methadone (n=12,
      30.8%). The main reasons given for the LAAM preference were that it produced less
      withdrawal (39.3%), fewer side effects (28.5%), less craving for heroin (17.9%),
      and entailed fewer pick-up days (14.3%). Those who chose LAAM had lower levels of
      heroin use during LAAM maintenance, significantly better outcomes on two sub
      scales of the SF-36 (Vitality and Mental Health), and reported that they felt
      more normal and that they were 'held' better when on LAAM. For those who chose
      methadone, there were no differences in outcomes between the LAAM and methadone
      maintenance periods. Preference for LAAM is associated with treatment outcomes as
      good or better than those with methadone.

PMID- 12062465
TI  - A longitudinal study of developmental trajectories to young adult cigarette
      smoking.
AB  - This study examined smoking trajectories between adolescence and adulthood in an
      African American cohort followed prospectively from first grade to age 32. We
      classified non-smokers, former smokers, current smokers/late adopters (initiated
      after age 18), and current smokers/early adopters (initiated before age 17).
      Results show that almost half of the population were currently smoking. Multiple
      logistic regression analyses showed that non-smokers differed most from the three
      smoking groups on social integration. Non-smokers were less likely to have left
      home before the age of 18, to have had more drug use parental supervision as an
      adolescent, to have moved less, and to attend church more frequently as an adult.
      Those current smokers who initiated early differed from the non-smokers and also
      from the former smokers and the current smokers who adopted smoking after the age
      of 18; they were more likely to be rated as aggressive or both shy and aggressive
      by their first grade teachers and to have drug problems as adults. Current
      smokers were less likely to attend church as adults than the non-smokers and
      former smokers. Neither mother's smoking or lifetime depression was related to
      smoking. The findings elucidate the contribution of factors over the life course
      that have an impact on smoking initiation, continuation, and cessation. They
      highlight the importance of targeting African American children and adolescents
      for prevention despite the fact that African American youth have the lowest rates
      of smoking across all ethnic groups. Possible interventions could be aimed at
      early aggressive behavior, parental supervision and monitoring, and other social
      integration efforts.

PMID- 12062466
TI  - Electrophysiological, behavioral and metabolical features of globus pallidus
      seizures induced by a microinjection of kainic acid in rats.
AB  - There has been few studies of the globus pallidus in relation to epilepsy. In
      this study, kainic acid (KA)-induced globus pallidus seizure was
      electrophysiologically, electroencephalographically, histopathologically and
      metabolically investigated in rats. Sixteen Wistar rats weighing 250-350 g were
      used. Under intraperitoneal pentobarbital anesthesia, a stainless-steel cannula
      was inserted stereotaxically into the left globus pallidus pars externa (GPe) for
      KA injection. For recording EEG, a depth electrode was inserted into the left
      GPe, just posterior to the tip of the injection guide cannula. Electrodes were
      also inserted into the right globus pallidus and bilateral sensorimotor cortex
      (SMC). EEG changes after KA injection were classified as follows: Continuous low
      voltage spikes were observed in the left GPe on EEG at stage 1. Intermittent
      multiple spikes and wave complexes began to propagate to the left SMC at stage 2.
      Continuous spikes and wave complexes began to propagate to the bilateral SMC at
      stage 3. Secondary generalized seizures were observed at stage 4. Globus pallidus
      seizures recurred every 7-9 min and lasted for 4-6 h. However, the seizures
      gradually subsided and became normal within 18 h. No spontaneous seizure was
      detected for the next 30 days. Histopathological study revealed a small gliotic
      lesion with neuronal cell loss around the cannula tip. Neither degeneration nor
      neuronal cell loss in the ipsilateral hippocampus were observed. The
      autoradiogram using [14C]2-deoxyglucose during seizure status demonstrated a
      remarkable increase of local cerebral glucose utilization not only in the GPe but
      also in the GPi. An increase glucose metabolism was also found in the follows:
      the medial and lateral septal nucleus, substantia nigra, hippocampus, frontal
      cortex, parietal cortex, piriform cortex, entorhinal cortex, accumbens nucleus,
      ventral and lateral nucleus of the thalamus, amygdala, and ventral nucleus of
      hypothalamus. KA injection into the unilateral GPe evoked not only epileptic
      excitation of the cortex but also transient enhancement of the globus pallidus
      substantia nigra circuit.

PMID- 12062467
TI  - Inferior colliculus unitary activity in wakefulness, sleep and under
      barbiturates.
AB  - The spontaneous unitary activity and the response to contralateral tone-burst
      were analyzed in the inferior colliculus (IC) of guinea pigs during the sleep
      waking cycle and under the effects of pentobarbital anesthesia. Minor changes
      were observed in both spontaneous and evoked activity between wakefulness (W) and
      slow wave sleep (SWS). On the other hand, a consistent increase in the mean
      spontaneous firing rate and a significant decrement in the signal-to-noise ratio
      (S/N ratio) was observed during paradoxical sleep (PS). Pentobarbital anesthesia
      reduced the spontaneous and evoked firing rate, the duration of the excitatory
      response and increased the duration of the post-excitatory suppression. We
      conclude, that the processing of auditory information in the IC change markedly
      during PS. Because the IC is a compulsory station for almost all the ascending
      auditory pathways, the observed decrease in the S/N ratio may deeply affect the
      auditory perception during this behavioral state. Finally, the alteration of the
      neuronal activity induced by pentobarbital differs not only with the activity
      observed during W, but also with the activity observed during both SWS and PS.

PMID- 12062468
TI  - Subcellular immunolocalization of NMDA receptor subunit NR1, 2A, 2B in the rat
      vestibular periphery.
AB  - The immunohistochemical localization of the NMDA glutamate receptor subunits NR1,
      NR2A, and NR2B was investigated in the rat vestibular periphery at the light and
      electron microscopy level using specific antipeptide antibodies. The afferent
      calyceal terminals and nerve fibers innervating type I vestibular hair cells were
      strongly NR1, NR2A, and NR2B immunoreactive. Under electron microscopy, the
      basolateral type I hair cell membrane was NR1 immunoreactive. The type II hair
      cell and its afferent boutons were NR1, NR2A, and NR2B non-immunoreactive. Nearly
      all of Scarpa's ganglion neurons were NR1 immunoreactive, but there was a subset
      of NR2A non-immunoreactive neurons. Additionally, the larger sized Scarpa's
      ganglia neurons were NR2B immunoreactive, while the smaller neurons were non
      immunoreactive. These findings are strong evidence for functional NMDA receptor
      mediation or modulation of afferent excitatory neurotransmission from type I but
      not type II vestibular hair cells to the primary afferent nerve. The receptor
      subtype(s) may be a combination of NR1/NR2A, NR1/NR2B, and/or NR1/NR2A/NR2B.

PMID- 12062469
TI  - Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral
      ischemia.
AB  - Alterations in factors involved in the regeneration of the neuronal network in
      the hippocampus of rats with microsphere embolism (ME) were examined. Nine
      hundred microspheres (48 microm in diameter) were injected into the right
      hemisphere, and immunochemical and immunohistochemical studies on the hippocampus
      were performed on the seventh day thereafter. Hematoxylin-eosin staining showed
      progressive and severe degeneration of the hippocampus after ME. The protein
      levels of brain-derived neurotrophic factor (BDNF), 43-kDa growth-associated
      protein (GAP-43), and adhesion protein L1 (L1) in the ipsilateral hippocampus of
      the ME animal, determined by Western blot analysis or enzyme immunoassay, were
      increased, unaltered, and decreased, respectively. In contrast, the
      immunohistochemical study showed increases in a marker of axonal sprouting GAP
      43, and a neurotrophic factor BDNF, and a decrease in an adhesion molecule L1 in
      some areas of the hippocampal ischemic penumbra of such animals. These results
      suggest that some factors for regeneration of the neuronal network in the
      ischemic penumbra responded to sustained cerebral ischemia for a certain period,
      although functional network of the nerve cells in the microsphere-injected
      hemisphere would be unlikely established after ME.

PMID- 12062470
TI  - MPP+ increases alpha-synuclein expression and ERK/MAP-kinase phosphorylation in
      human neuroblastoma SH-SY5Y cells.
AB  - Alpha-synuclein is a brain presynaptic protein that is linked to familiar early
      onset Parkinson's disease and it is also a major component of Lewy bodies in
      sporadic Parkinson's disease and other neurodegenerative disorders. Alpha
      synuclein expression increases in substantia nigra of both MPTP-treated rodents
      and non-human primates, used as animal models of parkinsonism. Here we describe
      an increase in alpha-synuclein expression in a human neuroblastoma cell line, SH
      SY5Y, caused by 5-100 microM MPP+, the active metabolite of MPTP, which induces
      apoptosis in SH-SY5Y cells after a 4-day treatment. We also analysed the
      activation of the MAPK family, which is involved in several cellular responses to
      toxins and stressing conditions. Parallel to the increase in alpha-synuclein
      expression we observed activation of MEK1,2 and ERK/MAPK but not of SAPK/JNK or
      p38 kinase. The inhibition of the ERK/MAPK pathway with U0126, however, did not
      affect the increase in alpha-synuclein. The highest increase in alpha-synuclein
      (more than threefold) in 4-day cultures was found in adherent cells treated with
      low concentrations of MPP+ (5 microM). Inhibition of ERK/MAPK reduced the damage
      caused by MPP+. We suggest that alpha-synuclein increase and ERK/MAPK activation
      have a prominent role in the cell mechanisms of rescue and damage, respectively,
      after MPP+ -treatment.

PMID- 12062472
TI  - Glutathione depletion in nigrostriatal slice cultures: GABA loss, dopamine
      resistance and protection by the tetrahydrobiopterin precursor sepiapterin.
AB  - Dopaminergic neurons in culture are preferentially resistant to the toxicity of
      glutathione (GSH) depletion. This effect may be due to high intrinsic levels of
      tetrahydrobiopterin (BH(4)). Here we studied the effects of manipulating GSH
      and/or BH(4) levels on selective neurotoxicity in organotypic nigrostriatal slice
      cultures. Following treatments with L-buthionine sulfoximine (BSO, 10-100 microM,
      2 days exposure, 2 days recovery), either alone or in combination with the BH(4)
      precursor L-sepiapterin (SEP, 20 microM), or the BH(4) synthesis inhibitor 2,4
      diamino-6-hydroxypyrimidine (DAHP, 5 mM), toxic effects were assessed by HPLC
      analysis of medium and tissues, cellular propidium iodide (PI) uptake, lactate
      dehydrogenase (LDH) efflux, as well as stereological counting of tyrosine
      hydroxylase (TH) positive cells. Thirty micromolar BSO produced 91% GSH and 81%
      GABA depletion and general cell death, but no significant effect on medium
      homovanillic acid (HVA) or tissue dopamine (DA) levels. SEP prevented or delayed
      GABA depletion, PI uptake and LDH efflux by BSO, whereas DAHP in combination with
      BSO caused (almost) complete loss of medium HVA, tissue DA and TH positive cells.
      We suggest that under pathological conditions with reduced GSH, impaired
      synthesis of BH(4) may accelerate nigral cell loss, whereas increasing
      intracellular BH(4) may provide protection to both DA and GABA neurons.

PMID- 12062471
TI  - Regulation of interstitial excitatory amino acid concentrations after cortical
      contusion injury.
AB  - Increases in brain interstitial excitatory amino acid (EAA(I)) concentrations
      after ischemia are ameliorated by use-dependent Na+ channel antagonists and by
      supplementing interstitial glucose, but the regulation of EAA(I) after traumatic
      brain injury (TBI) is unknown. We studied the regulation of EAA(I) after TBI
      using the controlled cortical impact model in rats. To monitor changes in EAA(I),
      microdialysis probes were placed in the cortex adjacent to the contusion and in
      the ipsilateral hippocampus. Significant increases in dialysate EAA(I) after TBI
      were found compared to levels measured in sham controls. Treatment with the use
      dependent Na+ channel antagonist 619C89 (30 mg/kg i.v.) did not significantly
      decrease dialysate glutamate compared to vehicle controls in hippocampus (10.4+/
      2.4 vs. 11.9+/-1.6 microM), but there was significant decrease in dialysate
      glutamate in cortex after 619C89 treatment (19.3+/-3 vs. 12.6+/-1.1 microM
      P<0.05). Addition of 30 mM glucose to the dialysate, a treatment that decreases
      EAA(I) after ischemia, had no significant effect upon dialysate glutamate after
      TBI in cortex (20.0+/-4.9 vs. 11.7+/-3.4 microM) or in hippocampus (10.9+/-2.0
      vs. 8.9+/-2.4 microM). These results suggest that neither increased release of
      EAAs due to Na+ channel-mediated depolarization nor failure of glutamate reuptake
      due to glucose deprivation can explain the majority of the increase in EAA(I)
      following TBI.

PMID- 12062473
TI  - Role of TRH receptors as possible mediators of analeptic actions of TRH-like
      peptides.
AB  - A large family of TRH-like peptides in the limbic region of rat brain including
      pGlu-Glu-Pro-NH(2) (EEP), pGlu-Val-Pro-NH(2) (Val(2)-TRH), Leu(2)-TRH, Phe(2)-TRH
      and Tyr(2)-TRH has recently been discovered. TRH (pGlu-His-Pro-NH(2)) has
      antidepressant, neuroprotective, analeptic, anticonvulsant, antiamnesic and
      euphoric properties, and other TRH-like peptides such as EEP exert several of
      these effects. A new TRH receptor (TRHR2) has been reported which is highly
      expressed in regions of rat brain that regulate attention and learning, arousal,
      sleep and processing of sensory information. The TRHR1 predominates in limbic
      structures involved in regulation of mood and in pituitary. This study examined
      the possibility that some of the newly discovered TRH-like peptides bind with
      high affinity to TRHR2, and that this receptor acts as the transducer for some of
      the CNS effects of this new class of neuropeptides. EEP, Val(2)-TRH and Leu(2)
      TRH were analeptics, like TRH, but Phe(2)-TRH and Tyr(2)-TRH were not. The
      affinity and efficacy of TRH-like peptides for TRHR1 and TRHR2 were measured in
      HEK293 cells stably expressing these receptors. The IC(50) values of TRH-like
      peptides for displacement of [3H]TRH from TRHR2 were TRH<<<(Leu(2)-, Phe(2)
      TRH)<(Gln(2)-, Ser(2)-TRH)<<(Val(2)-, Tyr(2)-, Arg(2)-, Thr(2)-, and Glu(2)-TRH).
      The IC(50) for Leu(2)-TRH was about 100 times that for TRH. When tested at the
      calculated IC(50) values, TRH-like peptides stimulated calcium responses in cells
      expressing TRHR1 and TRHR2, indicating that the peptides act as weak agonists at
      both receptors. These results indicate that TRHR1 and TRHR2 do not mediate the
      behavioral effects of TRH-like peptides.

PMID- 12062474
TI  - Sulfo-glycosaminoglycan content affects PHF-tau solubility and allows the
      identification of different types of PHFs.
AB  - Sulfo-glycosaminoglycans (sGAGs) are involved in the assembly of tau in at least
      a subpopulation of paired helical filaments (PHFs) in Alzheimer's disease (AD).
      To further understand the role of sGAG molecules in the structure of PHFs, we
      isolated PHFs from patients with AD and treated them with heparinase.
      Immunoelectron microscopy and Western blotting (WB) were used later on to analyze
      the changes obtained. The heparinase treatment abolished Tau14 and AT8
      immunodecoration (two N-terminal tau antibodies) and increased PHF-1 labeling (a
      C-terminal antibody). In addition, heparinase-treated filaments are more labile
      than control ones as demonstrated by sodium dodecyl sulfate-extraction and
      subsequent WB. In summary, our results demonstrate that sGAG content affects PHF
      conformation as well as PHF-tau solubilization.

PMID- 12062475
TI  - Distribution and differences of estrogen receptor beta immunoreactivity in the
      brain of adult male and female rats.
AB  - Studies have shown that estrogen plays important roles in regulating neural
      structure and function in the brain, but the mechanism remains unclear. The
      actions of estrogen were thought to be mediated by a single estrogen receptor
      until the identification of another estrogen receptor, namely estrogen receptor
      beta (ER-beta). Here we report a comprehensive study of the localization of ER
      beta immunoreactivity and differences in the brains of adult male and female rats
      on the basis of a nickel ammonium sulfate-enhanced immunocytochemical method
      using a polyclonal antiserum sc-8974. The results of these studies revealed: (1)
      ER-beta immunoactive material was mainly localized in the neuronal nucleus, but
      it was also detectable in the cytoplasm and neuronal processes; (2) in both male
      and female rats, high levels of ER-beta immunopositive signals were detected in
      the anterior olfactory nucleus, cerebral cortex, Purkinje cells, vertical limb of
      the diagonal band, red nucleus, locus ceruleus, and motor trigeminal nucleus.
      Moderate levels were found in the medial septum, lateral amygdaloid nucleus,
      substantia nigra, and central gray. Weak signals were localized in other
      subregions of the hypothalamus and amygdaloid complex; (3) there was an obvious
      difference of ER-beta immunoreactivity between male and female rats, and its
      intracellular distribution also showed a sex difference. The above results
      provide the first detailed evidence that ER-beta protein is widely distributed in
      both male and female rat brains, but that distinctive sex differences also exist.
      Estrogen may exert its function in different brain regions in a gender-specific
      manner.

PMID- 12062476
TI  - Picrotoxin and bicuculline have different effects on lumbar spinal networks and
      motoneurons in the neonatal rat.
AB  - Bicuculline is the most commonly used GABA(A) receptor antagonist to investigate
      the contribution of these receptors in motor control. However, this compound has
      been shown recently to potentiate the burst firing of neurons in various brain
      regions by blocking a calcium-activated potassium current underlying the spike
      after-hyperpolarization (AHP). This effect may distort our understanding of the
      role of GABA(A) receptors at the network level. In vitro brainstem-spinal cord
      preparations isolated from neonatal rats were used to compare the effects of
      bicuculline methiodide (bicuculline-M) and picrotoxin (PTX), another GABA(A)
      receptor antagonist, on the AHP of lumbar motoneurons as well as on spontaneous
      and locomotor-like motor activities. Intracellular recordings of lumbar
      motoneurons showed that bicuculline-M (20 microM) reduced the AHP to 57% of
      control whereas PTX (20-60 microM) had no significant effect. Bath-application of
      increasing concentrations of PTX caused an increase in spontaneous ventral root
      activity, which further increased significantly when bicuculline-M was added. The
      effects of both antagonists were tested on fictive locomotion. The left-right
      alternation was disrupted in the presence of bicuculline-M. A slow synchronous
      bursting activity of large amplitude also appeared in the presence of PTX. This
      slow rhythm was superimposed on a faster rhythm which still exhibited some degree
      of left-right alternation. These data demonstrate that bicuculline-M may not
      reveal accurately the contribution of GABA(A) receptors in motor control and the
      intrinsic properties of disinhibited networks.

PMID- 12062477
TI  - Potentiation of the excitatory action of NMDA in ventrolateral periaqueductal
      gray by the mu-opioid receptor agonist, DAMGO.
AB  - Several lines of evidence have suggested that mu-opioids, generally regarded as
      inhibitory, also have effects that stimulate neural activity. To look for
      possible excitatory opioid action in the rat periaqueductal gray (PAG), we first
      re-examined data from a previous study and found that met-enkephalin could evoke
      a delayed, sluggish excitation, suggestive of modulation by the opioid on the
      action of certain excitants. This observation, coupled with other studies that
      show mu-opioids can modulate NMDA receptor activation, prompted us to perform
      extracellular recording of the responses of single ventrolateral PAG (vlPAG)
      neurons in brain slices to DAMGO, a mu-opioid, and to NMDA. When applied alone,
      DAMGO at nM concentrations, like met-enkephalin, often evoked the delayed
      excitation and occasionally an inhibition. When applied after a brief exposure to
      NMDA, DAMGO at doses as low as 0.1 nM potentiated the excitation produced by a
      subsequent pulse of NMDA. This occurred, depending on cell type, in 23-100% of
      vlPAG neurons. The potentiating action of DAMGO was blocked by naloxone,
      suggesting it was mediated by mu-opioid receptors. Characterization of these mu
      opioid actions revealed that the potentiation and the delayed excitation, unlike
      the inhibition, was not blocked by another opioid antagonist, nalmefene, nor by
      an inhibitor of the G protein of the G(i) class, N-ethylmaleimide. Moreover, the
      potentiating action was distinct from the inhibition in that it was: (a) enhanced
      by repeated opioid applications, (b) exhibited low effective doses, (c) had a
      long time course (minutes to develop and last tens of minutes) and (d) was
      present in distinct though overlapping cell populations. These data reveal an
      unconventional action of opioids in PAG neurons, that is, a potentiation of
      excitation produced by NMDA. This effect appeared mechanistically distinct from
      opioid inhibition or disinhibition and may be related to established examples of
      direct opioid excitation. These observations may help understanding behaviorally
      important mechanisms linked to acute and chronic opioid functions in the vlPAG.

PMID- 12062478
TI  - Spinal administration of capsazepine inhibits noxious evoked responses of dorsal
      horn neurons in non-inflamed and carrageenan inflamed rats.
AB  - Vanilloid VR1 receptors are located in the dorsal horn of the spinal cord. The
      aim of the present study was to determine the role of spinal vanilloid receptors
      (VR1) during nociceptive processing in control and inflamed rats. Effects of
      spinal administration of capsazepine (0.5-30 microM/50 microl), a competitive VR1
      antagonist, on innocuous and noxious evoked responses of spinal neurones were
      studied in halothane anaesthetised rats. Transcutaneous electrical-evoked
      neuronal responses of spinal neurones were recorded in control and carrageenan
      (2%, 3 h) inflamed rats. Spinal application of capsazepine did not significantly
      alter Abeta-fibre evoked responses of neurones, however Adelta-fibre evoked
      responses were significantly inhibited by capsazepine in both non-inflamed and
      carrageenan inflamed rats (30 microM: non-inflamed 31+/-8% of control, P<0.01:
      carrageenan-inflamed 43+/-6% of control, P<0.01). Similarly, the evoked C-fibre
      mediated post-discharge responses of spinal neurones in non-inflamed and
      carrageenan inflamed rats were reduced by capsazepine (30 microM: non-inflamed
      41+/-14% of control, P<0.01: carrageenan-inflamed 31+/-9% of control, P<0.01).
      These results demonstrate a role of spinal VR1 receptors during noxious, but not
      innocuous transmission, at the level of the spinal cord. The degree of effect of
      capsazepine on evoked neuronal responses was similar in control and inflamed
      rats, suggesting that the role of spinal VR1 receptors is not altered following
      short-term peripheral inflammation. Our data suggest that following noxious
      peripheral stimulation, spinal VR1 receptors are activated, but the endogenous
      ligands mediating this effect remain to be elucidated.

PMID- 12062479
TI  - Bicuculline attenuates the MLR-induced suppression of dorsal horn neurons
      receiving group III afferent input.
AB  - In decerebrate cats, we found that iontophoretic application of bicuculline, a
      GABA(A) receptor antagonist, attenuated the mesencephalic locomotor region
      induced suppression of dorsal horn neurons responding to group III afferent input
      from the hindlimb. Our findings raise the possibility that GABA release onto
      dorsal horn neurons in the spinal cord may play an important role in the
      attenuation of the exercise pressor reflex by central command during exercise.

PMID- 12062480
TI  - Alcohol differentially affects c-Fos expression in the supraoptic nucleus of long
      sleep and short-sleep mice.
AB  - Ethanol administration in long-sleep (LS) and short-sleep (SS) mice results in a
      large number of Fos-IR neurons in the supraoptic nucleus (SON) in LS, and almost
      no Fos-IR neurons in the same nucleus in SS mice. In contrast, isotonic saline,
      hypertonic saline, with or without ethanol, resulted in a similar pattern of Fos
      IR in both strains. These data indicate a differential effect of ethanol on c-Fos
      signaling specifically in the SON. Since the LS and SS mice were specifically
      selected for differential sensitivity to the sedative/hypnotic effects of
      ethanol, this differential in c-Fos activity may be causally implicated in their
      differential sensitivity to ethanol.

PMID- 12062481
TI  - Amygdala kindling decreases insulin-like growth factor-I receptor binding sites
      in the rat hippocampus.
AB  - The neural excitability characteristic of kindling has been linked to structural
      alterations such as mossy fiber sprouting and synaptic reorganization within the
      hippocampus. Recent evidence suggests that growth factors may play a key role in
      kindling-related synaptic plasticity. Insulin-like growth factors-I and -II (IGF
      I/-II) and insulin are structurally-related pleiotropic growth factors known to
      be involved in neural growth and differentiation. In the present study, we
      investigated the effect of kindling on [125I]IGF-I, [125I]IGF-II and
      [125I]insulin receptor binding in the hippocampus of adult rats. Our results
      indicate a progressive decrease in [125I]IGF-I (but not [125I]IGF-II or
      [125I]insulin) binding sites in the CA1, hilus and the granule cell layer of the
      kindled rats compared to sham-stimulated rats. These results, in keeping with the
      established neurotrophic effects of IGF-I, suggest a potential role for this
      growth factor in mediating the structural alterations associated with kindling.

PMID- 12062482
TI  - Early decrease of the immunophilin FKBP 52 in the spinal cord of a transgenic
      model for amyotrophic lateral sclerosis.
AB  - Expressions of immunophilin FKBP-12 and FKBP-52 were examined in the spinal cord
      of transgenic mice with an ALS-linked mutant Cu/Zn superoxide dismutase (SOD1)
      gene. The immunoreactivity of FKBP-12 was present predominantly in the cytoplasm,
      but did not show a difference between age-matched wild type and transgenic (Tg)
      mice at 25 and 35 weeks. In contrast, the immunoreactivity of FKBP-52 was
      predominantly present in the nucleus, which progressively declined only in the Tg
      mice as early as an early presymptomatic stage at 25 weeks of age in the anterior
      horn neurons. The present result suggests that the downregulation of FKBP-52 may
      be involved in the pathogenesis in the early stages of amyotrophic lateral
      sclerosis (ALS).

PMID- 12062483
TI  - Activation of ATP receptor increases the cytosolic Ca(2+) concentration in
      ventral tegmental area neurons of rat brain.
AB  - ATP increased the cytosolic Ca(2+) concentration ([Ca](i)) in neurons of ventral
      tegmental area acutely dissociated from rat brain. The ATP response was dependent
      on external Ca(2+) and Na(+), and was blocked by voltage-dependent Ca(2+) channel
      blockers. The results suggest that the ATP-induced depolarization increases
      Ca(2+) influx via voltage-gated Ca(2+) channels resulting in the increase in
      [Ca](i).

PMID- 12062484
TI  - The selective neurokinin (NK)(1) antagonist, GR205,171, stereospecifically
      enhances mesocortical dopaminergic transmission in the rat: a combined dialysis
      and electrophysiological study.
AB  - Upon acute, systemic administration, the selective, non-peptidergic NK(1)
      receptor antagonist, GR205,171, dose-dependently enhanced the firing rate of
      ventrotegmental dopaminergic neurones. Dialysate levels of dopamine were
      increased in the frontal cortex, but not in the striatum and nucleus accumbens,
      of conscious rats. These actions were stereospecific in that its less-active
      isomer, GR226,206, was ineffective. Further, they were selective for dopaminergic
      pathways inasmuch as the firing rate of dorsal raphe serotonergic neurones and
      dialysate levels of serotonin were unaffected by GR205,171. Activation of
      mesocortical dopaminergic pathways may be involved in the influence of NK(1)
      antagonists upon mood.

PMID- 12062486
TI  - Evidence for de novo sphingolipid biosynthesis in Toxoplasma gondii.
AB  - Glycolipids are important components of cellular membranes involved in various
      biological functions. In this report, we describe the identification of the de
      novo synthesis of glycosphingolipids by Toxoplasma gondii tachyzoites. Parasite
      specific glycolipids were identified by metabolic labelling of parasites with
      tritiated serine and galactose. These glycolipids were characterised as
      sphingolipids based on the labelling protocol and their insensitivity towards
      alkaline treatment. Synthesis of parasite glycosphingolipids were inhibited by
      threo-phenyl-2-palmitoylamino-3-morpholino-1-propanol and L-cycloserine, two well
      established inhibitors of de novo sphingolipid biosynthesis. The identified
      glycolipids were insensitive towards treatment with endoglycoceramidase II
      indicating that they might belong to globo-type glycosphingolipids. Taken
      together, we provide evidence for the first time that T. gondii is capable of
      synthesising glycosphingolipids de novo.

PMID- 12062485
TI  - Lipid metabolism in mucous-dwelling amitochondriate protozoa.
AB  - Entamoeba, Giardia, and trichomonads are the prominent members of a group known
      as 'mucosal parasites'. While Entamoeba and Giardia trophozoites colonise the
      small intestine, trichomonads inhabit the genitourinary tracts of humans and
      animals. These protozoa lack mitochondria, well-developed Golgi complexes, and
      other organelles typical of higher eukaryotes. Nonetheless, they have developed
      unique metabolic pathways that allow them to survive and multiply in the small
      intestine and reproductive tracts by scavenging nutrients from the host. Various
      investigators have shown that these protozoa are unable to synthesise the
      majority of their own lipids and cholesterol de novo; rather, they depend mostly
      on supplies from outside sources. Therefore, questions of how they transport and
      utilise exogenous lipids for metabolic purposes are extremely important. There is
      evidence suggesting that these parasites can take up the lipids and cholesterol
      they need from lipoprotein particles present in the host and/or in the growth
      medium. Studies also support the idea that individual lipid and fatty acid
      molecules can be transported without the help of lipoproteins. Exogenous
      phospholipids have been shown to undergo fatty acid remodelling (by
      deacylation/reacylation reactions), which allows these protozoa to alter lipids,
      bypassing the synthesis of entirely new phospholipid molecules. In addition, many
      of these amitochondriates are, however, capable of elongating/desaturating long
      chain fatty acids, and assembling novel glycophospholipid molecules. In this
      review, progress in various aspects of lipid research on these organisms is
      discussed. Attempts are also made to identify steps of lipid metabolic pathways
      that can be used to develop chemotherapeutic agents against these and other
      mucosal parasites.

PMID- 12062487
TI  - 14-3-3 proteins in Schistosoma mansoni; identification of a second epsilon
      isoform.
AB  - A new member of the 14-3-3 protein family in Schistosoma mansoni has been
      identified. Sequence analysis demonstrated that this protein is a member of the
      epsilon sub-group and is the orthologue of Schistosoma japonicum 14-3-3epsilon.
      Since we had previously identified a 14-3-3epsilon protein from S. mansoni, we
      termed the original protein 14-3-3epsilon-1 and this second epsilon protein 14-3
      3epsilon-2. Schistosoma mansoni encodes at least four different 14-3-3 isoforms:
      the two epsilon proteins and 14-3-3 protein 1 and protein 2, which are zeta-like
      isoforms. Phylogenetic analysis demonstrated the early divergence of the epsilon
      isoforms, and that schistosome proteins 1 and 2 are among the oldest non-epsilon
      14-3-3 proteins yet identified. Schistosoma mansoni 14-3-3epsilon-1, 14-3
      3epsilon-2, and protein 1 are stage specifically expressed in a similar manner,
      being absent in cercariae and schistosomula, and abundant in lung stage and adult
      male and female worms. Protein 2 transcript was not detected at any of the life
      cycle stages examined. All three detected 14-3-3 isoforms elicit an immune
      response during infection, with the greatest response directed against protein 1.
      Binding studies with S. mansoni receptor kinase-1 (SmRK1) and human Raf kinase
      revealed that the three 14-3-3epsilon isoforms exhibit a preference for target
      protein binding. Although all three isoforms do bind to both targets, 14-3-3
      protein 1 interacts most strongly with Raf, whereas the 14-3-3-1 isoform binds
      SmRK1 preferentially. These results suggest that the individual 14-3-3 proteins
      may have evolved to play isoform-specific roles in the development and survival
      of S. mansoni within its host.

PMID- 12062488
TI  - Vero cell surface proteoglycan interaction with the microneme protein NcMIC(3)
      mediates adhesion of Neospora caninum tachyzoites to host cells unlike that in
      Toxoplasma gondii.
AB  - Neospora caninum and Toxoplasma gondii are characterised by a very low host cell
      specificity, thus they are able to infect a wide range of different cells in vivo
      and in vitro. Infection of the host cell by tachyzoites is a process which is
      preceded by adhesion onto the host cell surface. The receptors on the host cell
      surface which would allow N. caninum to establish a physical interaction have not
      been investigated so far. Here we report the role of host cell surface
      proteoglycans as receptors for the adhesion of N. caninum tachyzoites to Vero
      cell monolayers. We found that N. caninum tachyzoites, similar to T. gondii
      tachyzoites, can bind to sulphated proteoglycans which naturally occur on the
      surface of mammalian cells, including heparin/heparan sulphate, chondroitin
      sulphates, as well as to the artificially sulphated glycosaminoglycan dextran
      sulphate. Although removal of heparan sulphate from the host cell surface results
      in decreased adhesion of T. gondii tachyzoites, binding of N. caninum tachyzoites
      is not affected by this treatment. Conversely, enzymatic removal of chondroitin
      sulphate A, B and C decreases N. caninum adhesion but does not affect T. gondii
      binding to Vero cells. Thus, T. gondii and N. caninum tachyzoites exhibit
      differential adhesive properties with regard to host cell surface
      glycosaminoglycans. Additional experiments employing Triton X-100 solubilised
      NcSRS2 and NcMIC3 showed that NcSRS2 binds to the host cell surface, but not
      through those sulphated glycosaminoglycans investigated in this study. In
      contrast, NcMIC3 binding to the host cell surface is dramatically influenced by
      these modifications. Further experiments showed that the NcMIC3 adhesive motif
      comprised of four consecutive epidermal growth factor-like domains expressed as a
      recombinant protein exhibits a high binding activity for sulphated
      glycosaminoglycans. These results suggest that host cell surface proteoglycan
      interaction of N. caninum differs from that observed for T. gondii, and that the
      epidermal growth factor-like adhesive motif in NcMIC3 could be involved in this
      process.

PMID- 12062489
TI  - Age-grading and growth of Wuchereria bancrofti (Filariidea: Onchocercidae) larvae
      by growth measurements and its use for estimating blood-meal intervals of its
      Polynesian vector Aedes polynesiensis (Diptera: Culicidae).
AB  - Growth in length and width of Wuchereria bancrofti (Filariidea: Onchocercidae)
      larvae developing in its Polynesian vector Aedes polynesiensis (Diptera:
      Culicidae) was analysed using a mathematical approach to objectively extract
      patterns. L1 had a U-shaped growth in length, while widths followed an S-shaped
      function. L2 had an S-shaped growth in length and width. Growth in length of L3
      was also S-shaped, while widths had an asymptotic size following a period of
      rapid shrinkage. The greatest difference between length and width was in stage 3
      where the length was over 75 times greater than the width. The ratio of length to
      width was approximately 50 for microfilariae and only 10 for the L1 ('sausage')
      stage. Characteristic mean length (and width) were approximately 280(7) microm
      for microfilariae, approximately 181 microm for L1 at their smallest, and
      approximately 1584(22) microm for L3 infective larvae. There was a great increase
      in length during stage 2 from approximately 322(27) to approximately 982(31)
      microm. Stage duration decreased with increasing temperature while growth rate
      increased, giving steeper growth curves. There was no effect of temperature on
      size, except for L3, which were shorter when mosquitoes were reared at higher
      temperature. It appears that larval growth is a continuous process from
      microfilariae to the young L3 stage, and continuously modifies the larval
      parasite aspect, even within each stage. Thus, information on larval shape may be
      used as an age indicator and in some cases, may give an estimation on time
      elapsed since infection of the vector. An important demographic parameter used in
      most mathematical models describing transmission of parasites by insect vectors
      is the length of the gonotrophic cycle of the vector, i.e. the time interval
      between two successive blood-meals. Usual methods for computing such a parameter
      are based on mark-recapture techniques. However, reliable estimates need
      substantial capture rates, which are not always possible. This paper presents
      another approach in which marked mosquitoes are those naturally infected by W.
      bancrofti. For one mosquito, the time since infection is simply the age of the
      developing larval parasite. Our method first expresses the age of larval parasite
      as a fraction of total development time (from microfilariae entering the vector
      to L3 larvae) using a regression model based on measurements of the parasite's
      length and width. This fraction of development is then converted to a
      chronological age since infection, using a back-calculation procedure involving
      ambient temperatures and growth rates of W. bancrofti larvae in the vector. The
      method is applied to wild caught Ae. polynesiensis in French Polynesia to compute
      the length of the gonotrophic cycle. This mosquito species comes to bite
      approximately 3, 6-7 and 9 days after a first infectious blood-meal. Then the
      length of the gonotrophic cycle may be of 3-4 days.

PMID- 12062490
TI  - Dauer juvenile longevity and stress tolerance in natural populations of
      entomopathogenic nematodes: is there a relationship?
AB  - Qualitative and quantitative genetic analysis of life span in experimental adult
      animals predicts that resistance to stress and longevity are positively
      correlated, but such studies on field populations of animals are rare. We tested
      this hypothesis using dauer juveniles of 15 natural populations of the
      entomopathogenic nematode, Heterorhabditis bacteriophora, collected from diverse
      localities. Dauer juvenile longevity at 25 degrees C in autoclaved tap water and
      tolerance to major environmental stresses including heat (survival at 40 degrees
      C for 2 h), ultraviolet (UV) radiation (original virulence remaining after
      exposure to 302 nm UV for 5 min), hypoxia (survival at approximately 0% dissolved
      O2 at 25 degrees C for 96 h), and desiccation (survival in 25% glycerol at 25
      degrees C for 72 h) differed significantly among populations. Intrinsic dauer
      juvenile longevity, defined as the number of weeks to 90% mortality (LT90)
      estimated using probit analysis of nematode survival data at 25 degrees C varied
      between 6 and 16 weeks among populations. Longevity was most strongly correlated
      with heat followed by UV and hypoxia tolerance, respectively, but showed no
      correlation with desiccation tolerance. The strong positive correlation of
      longevity with heat tolerance was further confirmed through principal components
      analysis which showed almost identical variance for heat and longevity. Among the
      stress factors, only UV tolerance was positively correlated with heat and hypoxia
      tolerance. Differences in longevity and stress tolerance in nematode populations
      isolated from a single 200 m2 grassland locality further support another
      hypothesis that population structure of heterorhabditid nematodes is highly
      fragmented, thus suggesting the existence of metapopulation dynamics.

PMID- 12062491
TI  - Genomic organisation and transcription characterisation of the gene encoding
      Leishmania (Leishmania) amazonensis arginase and its protein structure
      prediction.
AB  - The genomic organisation of the gene encoding Leishmania (Leishmania) amazonensis
      arginase as well as its flanking regions were characterised. The size of the
      transcribed RNA was determined, allowing us to map the genomic sites signalling
      for RNA trans-splicing and putative polyadenylation regions. The general
      organisation was compared with genes encoding other proteins already described in
      organisms of the Trypanosomatid family. The complete nucleotide sequence of the
      arginase open reading frame was obtained and the three-dimensional structure of
      the enzyme was inferred by a computational analysis of the deduced amino acid
      sequence, based on the established crystal structure described for Rattus
      norvergicus arginase. The human liver arginase sequence was analysed in the same
      way and the comparison of the presumed structure of both the Leishmania and human
      enzymes identified some differences that may be exploited in chemotherapeutic
      studies.

PMID- 12062492
TI  - Plasmodium falciparum protein phosphatase type 1 functionally complements a glc7
      mutant in Saccharomyces cerevisiae.
AB  - We have identified a new homologue of protein phosphatase type 1 from Plasmodium
      falciparum, designated PfPP1, which shows 83-87% sequence identity with yeast and
      mammalian PP1s at the amino acid level. The PfPP1 sequence is strikingly
      different from all other P. falciparum Ser/Thr phosphatases cloned so far. The
      deduced 304 amino acid sequence revealed the signature sequence of Ser/Thr
      phosphatase LRGNHE, and two putative protein kinase C and five putative casein
      kinase II phosphorylation sites. Calyculin A, a potent inhibitor of Ser/Thr
      phosphatase 1 and 2A showed hyperphosphorylation of a 51kDa protein among other
      parasite proteins. Okadaic acid on the other hand, was without any effect
      suggesting that PP1 activity might predominate over PP2A activity in intra
      erythrocytic P. falciparum. Complementation studies showed that PfPP1 could
      rescue low glycogen phenotype of Saccharomyces cerevisiae glc7 (PP1) mutant,
      strongly suggesting functional interaction of PfPP1 and yeast proteins involved
      in glycogen metabolism.

PMID- 12062493
TI  - HcSTK, a Caenorhabditis elegans PAR-1 homologue from the parasitic nematode,
      Haemonchus contortus.
AB  - A putative serine/threonine protein kinase (HcSTK) from the parasitic nematode
      Haemonchus contortus was characterised at the mRNA and amino acid levels. HcSTK
      displays a high level of identity (85-93% in the catalytic domain) with proteins
      of the PAR-1/MARK serine/threonine protein kinase (STK) subfamily, which
      represent signal transduction molecules involved in establishing and maintaining
      polarity in proliferating and differentiating cells. The transcript of hcstk is
      expressed in different developmental stages (second-, third-, fourth-stage larvae
      and adults) and various organs (muscle, intestine and reproductive) of H.
      contortus. In addition, there are several isoforms which appear to relate to a
      single gene. The expression profile of hcstk is similar to that of Caenorhabditis
      elegans PAR-1, and the level of sequence identity among members of the PAR-1/MARK
      STK subfamily, representing a range of species of vertebrates (e.g. humans and
      rodents), invertebrates (e.g. insects and C. elegans) and yeast, suggests that
      HcSTK may be involved in a conserved signal transduction pathway.

PMID- 12062495
TI  - Detection of the initial infective stages of the protozoan parasite Marteilia
      sydneyi in Saccostrea glomerata and their development through to sporogenesis.
AB  - DNA probes were used in in situ hybridisation on histological sections of oysters
      exposed for defined intervals to Marteilia sydneyi infection to reveal the early
      development of the parasite in the oyster host, Saccostrea glomerata. The initial
      infective stages enter through the palps and gills whereupon extrasporogonic
      proliferation results in the liberation of cells into surrounding connective
      tissue and haemolymph spaces. Following systemic dissemination, the parasite
      infiltrates the digestive gland and becomes established as a nurse cell beneath
      the epithelial cells in a digestive tubule. Here, cell-within-cell proliferation
      results in the eventual liberation of daughter cells from the nurse cell into
      spaces between adjacent epithelial cells. None of these stages had previously
      been described. Proliferation is associated with host responses, including
      haemocytic infiltration of the connective tissue and diapedesis across tubule
      epithelia. The responses cease as sporogenesis begins.

PMID- 12062494
TI  - Reduction in the prevalence and intensity of hookworm infections after
      praziquantel treatment for schistosomiasis infection.
AB  - Praziquantel exhibits activity against all major human schistosome parasites and
      has become the cornerstone for treatment and morbidity control of
      schistosomiasis. Praziquantel is also active against a wide range of trematodes,
      human and veterinary cestodes and displays cysticidal effects. To the best of our
      knowledge anthelminthic properties have never been documented. Here, we report a
      study among 96 schoolchildren from an area highly endemic for Schistosoma mansoni
      and hookworm infection, and place particular emphasis on the effect of
      praziquantel on the prevalence and intensity of hookworm infections. Stool
      specimens were screened over several consecutive days prior and 4 weeks after
      systematic administration of praziquantel. We found a significant reduction in
      the prevalence of hookworm infection from 75.0 to 40.6% (odds ratio (OR)=0.21;
      95% confidence interval (CI): 0.11-0.40). Infection intensities, expressed by
      geometric mean egg counts of all children, were also reduced significantly from
      10.7 to 2.0 eggs per gram stool (paired t-test=7.78, P<0.001). If these findings
      are confirmed in other epidemiological settings - following a similarly sensitive
      diagnostic approach - they might become of considerable relevance. In areas where
      both schistosome and hookworm coexist, and praziquantel is being recommended for
      schistosomiasis control, large-scale application of this drug might also reduce
      the burden of hookworms.

PMID- 12062496
TI  - The influence of medium-chain triglycerides on the stability of all-in-one
      formulations.
AB  - When mixed with parenteral nutrients as an all-in-one admixture, previous data
      have demonstrated that lipid emulsions composed of medium-chain triglycerides
      (MCTs) and long-chain triglycerides (LCTs) yield more stable formulations
      compared with those compounded with pure LCT lipid emulsions. We investigated the
      physical stability of various preparations of intravenous lipid emulsions as all
      in-one admixtures. Each final lipid emulsion used to compound the all-in-one
      formulation was a 20% w/v mixture containing MCTs and LCTs as either a single
      emulsion containing both triglycerides, or an emulsion made extemporaneously from
      separate starting emulsions of pure MCT and LCT. The first emulsion was composed
      of a 50:50 (by weight) physical mixture of MCTs and LCTs, and consisted of 50%
      MCT:40% omega-6 LCT (soybean oil):10% omega-3 LCT (fish oil) that was available
      as a single 20% w/v lipid emulsion. The second and third emulsions were specially
      prepared from separate stock dispersions containing pure 20% w/v MCT and pure 20%
      w/v LCT (soybean oil) lipid emulsions, and were made in volume ratios of 75%
      MCT:25% omega-6 LCT and 50% MCT:50% omega-6 LCT, respectively. This was done in
      order to investigate whether the method of emulsion preparation and/or ratio of
      MCT to LCT influenced all-in-one admixture stability. Each all-in-one admixture
      was studied at four intervals over 30 h at room temperature conditions by light
      extinction (or obscuration) using a single-particle optical sensing (LE/SPOS)
      technique. The data, performed in duplicate at each interval, is expressed as the
      volume-weighted percent of fat (PFAT) globules >5 microm. The results confirm the
      stabilizing effects of MCTs when made as a physical oil mixture as a single lipid
      emulsion. However, stabilization is lost if the MCT and LCT emulsions are mixed
      from separate starting emulsions and then compounded as an all-in-one
      formulation. The extemporaneous mixing of commercial lipid emulsions is not
      recommended.

PMID- 12062497
TI  - Influence of polyethylene glycol and povidone on the polymorphic transformation
      and solubility of carbamazepine.
AB  - PURPOSE: Influence of polymers on the polymorphic transition of drugs has
      received limited attention in the literature. The main objective of this study
      was to gain an understanding of the influence of polyethylene glycol and povidone
      on the crystalline modification and subsequently the solubility of carbamazepine
      in solid dispersions. METHODS: The physical state of the drug within the
      dispersions was determined using DSC and powder X-ray diffractometer. DSC and
      optical microscopy was used to study the kinetics and morphology of dihydrate
      formation, respectively. RESULTS: Both the polymeric dispersions showed an
      improved dissolution profile for carbamazepine. Carbamazepine was present in an
      amorphous form within the povidone dispersions. In contrast, the PEG dispersions
      showed the presence of crystalline drug. Higher ratios of drug/PEG resulted in
      the metastable form I of carbamazepine. Dihydrate formation from both the
      polymeric dispersions was higher compared with pure carbamazepine. The physical
      state of the drug and the amount of drug in solution accounted for the higher
      dihydrate formation from these dispersions. CONCLUSIONS: Knowledge of the factors
      contributing to enhanced solubility is critical to the stability of solid
      dispersions. Additionally, influence of polymers like povidone on the crystalline
      transitions of polymorphic drugs may be crucial during its use as a binder in
      granulation.

PMID- 12062498
TI  - Molecular-weight-dependent pharmacokinetics and cytotoxic properties of cisplatin
      complexes prepared with chondroitin sulfate A and C.
AB  - In order to screen out an optimum complex for reducing the nephrotoxicity of
      cisplatin (CDDP), we investigated and compared CDDP-chondroitin sulfate complexes
      to CDDP in terms of in vivo pharmacokinetics and in vitro cytotoxicity. The
      polymeric carriers used in the study were chondroitin sulfate A (CSA, 4-sulfate)
      with mean molecular weights of 10 kDa (CSA-1) and 23 kDa (CSA-2), and chondroitin
      sulfate C (CSC, 6-sulfate) with mean molecular weights of 8 kDa (CSC-1) and 25
      kDa (CSC-2). The resultant complexes (CDDP-CSA-1, CDDP-CSA-2, CDDP-CSC-1 and CDDP
      CSC-2) were administered intravenously to rats. The obtained plasma concentration
      time curves during the 3 h period studied for all complexes are biphasic. The
      plasma dispositions of complexes were dependent on the molecular sizes with
      urinary excretion as main elimination pathway. CDDP-CSA-1 and CDDP-CSC-1 were
      unable to effectively increase the plasma retention of platinum due to rapid
      renal excretion. Furthermore, CDDP-CSA-1 disappeared from plasma more quickly
      than CDDP-CSC-1. CDDP-CSA-2 and CDDP-CSC-2, with similar urinary excretion as
      CDDP, gave rise to approximately five and four-fold increase in AUC(0-3 h)
      values, respectively, than that was achieved with native CDDP treatment.
      Biodistribution was compared between CDDP-CSA-2 and CDDP-CSC-2. Both complexes
      effectively suppressed the extensive distribution of CDDP into most tissues,
      especially kidney. However, CDDP-CSC-2 showed less reduction effect than CDDP-CSA
      2. In addition, a significantly higher accumulation in tumor tissue was found
      with the administration of CDDP-CSA-2 than CDDP. Moreover, CSA complexes
      displayed an IC(50) of 6 microM Pt-equivalents against SW4800 human colon cancer
      cells, similar to that of CDDP, whereas CSC complexes were less active than CDDP.
      These studies indicate that the complex prepared with CSA, which is greater than
      20 kDa of molecular size, is superior to that of CSC, exhibiting improved
      pharmacokinetics and similar pharmacological activity to the native drug.

PMID- 12062499
TI  - The enhancement of pipemidic acid permeation into the pig urinary bladder wall.
AB  - The influence of interactions between polycarbophil and calcium on a model drug
      permeation into the pig urinary bladder wall was investigated. Pipemidic acid was
      used as a model drug. One percent w/v polycarbophil dispersion significantly
      increases the permeation of pipemidic acid into the urinary bladder wall. The
      enhanced absorption of pipemidic acid caused by polycarbophil is significantly
      less pronounced in polycarbophil dispersions containing calcium. The enhancement
      of pipemidic acid permeation into the urinary bladder wall could be due to the
      opening of tight junctions, which causes higher paracellular permeability. In the
      case of polycarbophil dispersion with calcium some carboxylic groups of polymer
      are already occupied with calcium, present in the dispersions. As a consequence
      extracellular calcium binds to polycarbophil in lower extent if compared with
      polycarbophil dispersion without calcium and transport is increased to a lesser
      degree. We concluded that the mechanism of drug absorption enhancement caused by
      polycarbophil could be similar for urinary bladder as described in the literature
      for intestinal mucosa.

PMID- 12062500
TI  - Non-linear mixed effects models for the evaluation of dissolution profiles.
AB  - The use of non-linear mixed effects models to describe dissolution data has been
      evaluated. A theoretical part is included to introduce this approach to
      scientists who are not familiar with this type of statistics. The standard
      settings of the statistical software package (S-plus) are used as much as
      possible. Several mathematical functions like the Weibull, logistic, first-order
      and Gompertz are employed as basis for the non-linear mixed effects models.
      Examples are given using dissolution data of immediate and extended release
      tablets. The results are compared with those obtained using linear mixed effects
      models.

PMID- 12062501
TI  - Iontophoretic estradiol skin delivery and tritium exchange in ultradeformable
      liposomes.
AB  - This work evaluated the in vitro transdermal iontophoretic delivery of tritiated
      estradiol from ultradeformable liposomes compared with saturated aqueous solution
      (control). Effects of current density and application time on tritium exchange
      with water were also determined. Penetration studies used three Protocols.
      Protocol I involved occluded passive steady state estradiol penetration from
      ultradeformable liposomes and control. The effect of current densities on drug
      penetration rates was also assessed (Protocol II). In Protocol III, three
      consecutive stages of drug penetration (first passive, iontophoresis and second
      passive) through the same human epidermal membranes were monitored. Such an
      experimental design investigated the possible effect of high current density (0.8
      mA/cm(2)) on skin integrity. The tritium exchange study showed that extent of
      exchange correlated well with current density and time of application, with some
      shielding of estradiol by the liposomal structure. Liposomes enhanced estradiol
      passive penetration after occlusion. Protocol II showed that estradiol flux
      increased linearly with current density, although being delivered against
      electroosmotic flow. In Protocol III, reduction in flux of the second passive
      stage to near that of the first reflected a reversibility of the structural
      changes induced in skin by current.

PMID- 12062502
TI  - Chemical characterisation of sodium starch glycolate particles.
AB  - The internal and surface chemical compositions of three sodium starch glycolate
      (SSG) products, Explotab, Primojel and Vivastar P were studied using scanning
      electron microscopy (SEM), energy dispersive X-ray analysis (EDX), time of flight
      secondary ion mass spectrometry (TOF-SIMS) and 23Na nuclear magnetic resonance
      spectroscopy (NMR). The surfaces of Explotab and Primojel contained very distinct
      features containing Na and Cl, however, Primojel also contained features which
      contained Na which may reflect the presence of Na glycolate and/or Na citrates.
      Vivastar P contained relatively few surface Cl containing features. Analysis of
      cross-sections of the particles showed that Na appeared to be uniformly
      distributed throughout the particles of all the products. Additionally, there was
      a significant concentration of Cl in the periphery of Explotab and Primojel. In
      the case of Vivastar P, significant levels of Na and Cl were detected in the
      internal regions of the particles which, together with 23Na NMR, suggests that
      NaCl is uniformly distributed within Vivastar P. 23Na NMR also suggested that the
      ratio of organic Na to NaCl was considerably lower in Vivastar P than Primojel
      and Explotab. Overall, even though all these three products satisfy the
      pharmacopeial descriptions of SSG, these studies suggest that Primojel and
      Explotab exhibit different chemical compositions to Vivastar P. Since the three
      products studied are reported to be prepared from potato starch, the apparent
      differences in chemical composition probably reflect the different manufacturing
      processes used, however, batch to batch variations may account for some of the
      subtle differences.

PMID- 12062503
TI  - In vivo evaluation of matrix pellets containing nanocrystalline ketoprofen.
AB  - The aim of this study was to evaluate the in-vivo behaviour of matrix pellets
      formulated with nanocrystalline ketoprofen after oral administration to dogs. No
      significant differences in AUC-values were seen between pellet formulations
      containing nanocrystalline or microcrystalline ketoprofen and a commercial
      ketoprofen formulation (reference: Rofenid 200 Long Acting). C(max) of the
      formulations containing nano- or microcrystalline ketoprofen was significantly
      higher compared to reference, whereas t(max) was significantly lower. The in-vivo
      burst release observed for the spray dried nanocrystalline ketoprofen matrix
      pellets was reduced following compression of the pellets in combination with
      placebo wax/starch pellets. These matrix tablets sustained the ketoprofen plasma
      concentrations during 5.6 and 5.4 h for formulations containing nano- and
      microcrystalline ketoprofen, respectively.

PMID- 12062505
TI  - Liposome clearance in mice: the effect of a separate and combined presence of
      surface charge and polymer coating.
AB  - The purpose of our work was to compare the biodistribution of liposomes with
      different surface properties. Phosphatidylcholine (PC)/cholesterol (Chol)
      liposomes were prepared containing 6% mol of a charged lipid (stearylamine, SA;
      phosphatidic acid, PA; or phosphatidyl serine, PS) and/or polyethylene glycol
      (PEG)-PE of different MW (750 and 5000). zeta-Potentials and liposome clearance
      in mice were investigated. In vitro, the attachment of PEG in a similar fashion
      neutralizes the effect of any charged component. In vivo, the chemical nature of
      a charged lipid becomes important. Both short PEG750 and longer PEG5000 inhibit
      the clearance of positively charged SA-liposomes, while only longer PEG5000
      inhibits the clearance of negatively charged PA-liposomes and none of the PEGs
      inhibit the clearance of negatively charged PS-liposomes. The opsonins with
      different molecular size may be involved in the clearance of liposomes containing
      different charged lipids.

PMID- 12062504
TI  - Vitamin A and vitamin A palmitate stability over time and under UVA and UVB
      radiation.
AB  - Vitamin A and vitamin A palmitate photostability were tested in different media.
      Ethanol and octyl octanoate solutions of these two vitamins, as such and with the
      addition of sunscreens (3,4 methylbenzilidencanfora, butyl methoxy
      dibenzoylmethane and octyl methoxycinnamate) or beta-carotene and butylated
      hydroxy toluene, were analysed spectrophotometrically after UVB or UVA
      irradiation. An O/W fluid emulsion with 0.5% w/w of retinyl palmitate, with and
      without butylated hydroxy toluene, was prepared. The oil containing the vitamin
      was extracted with HCl and aluminium sulfate and analysed spectrophotometrically
      after UVB or UVA irradiation. The fluid emulsion containing retinyl palmitate
      with and without butylated hydroxy toluene was stored at different temperatures
      and analysed every week spectrophotometrically for a month. Of the sunscreens
      tested butyl methoxy dibenzoylmethane showed the strongest protective action
      towards vitamin A and vitamin A palmitate, whereas beta-carotene did not protect
      either vitamin. Butylated hydroxy toluene inhibited the photodegradation of both
      vitamins dissolved in octyl octanoate, suggesting that oxygen may be involved in
      their degradation. O/W emulsion promoted slightly the degradation of vitamin A
      ester. Butylated hydroxy toluene protected retinyl palmitate from degradation
      induced by light and heat.

PMID- 12062506
TI  - Optimization of a self-nanoemulsified tablet dosage form of Ubiquinone using
      response surface methodology: effect of formulation ingredients.
AB  - The objectives of the present study were (1) to evaluate the effect of
      formulation ingredients on the release rate of Ubiquinone from its adsorbing
      solid compact; and (2) to prepare and evaluate an optimized self-nanoemulsified
      tablet formulation. A three factor, three-level Box-Behnken design was used for
      the optimization procedure, with the amounts of copolyvidone (X(1)), maltodextrin
      (X(2)) and microcrystalline cellulose (X(3)) as the independent variables. The
      response variable was cumulative percent of Ubiquinone emulsified in 45 min with
      constraints on weight, flowability index, tensile strength, friability and
      disintegration time of the dry powdered emulsion and the resultant compact. Based
      on the experimental design, different Ubiquinone release rates and profiles were
      obtained. Mathematical equations and response surface plots were used to relate
      the dependent and independent variables. The regression equation generated for
      the cumulative percent emulsified in 45 min was Y(6)=64.10-12.32X(1)-4.36X(2)
      25.53X(3)+6.99X(1)X(2)+3.97X(1)X(3)+9.70X(2)X(3)
      8.98X(1)(2)16.22X(2)(2)+17.10X(3)(2). The optimization model predicted an 85.4%
      release with X(1), X(2) and X(3) levels of 66.6, 560.1 and 100, respectively. A
      new formulation was prepared according to these levels. The observed responses
      were in close agreement with the predicted values of the optimized formulation.

PMID- 12062507
TI  - Feline leishmaniosis due to Leishmania infantum in Italy.
AB  - A case of leishmaniosis in domestic cats (Felis catus domesticus) is described.
      The subject showed a nodular lesion on the eyelid. The diagnosis was achieved by
      serological, parasitological, and light and electron microscopic investigations.
      By molecular techniques the aetiological agent was identified as belonging to
      Leishmania infantum, the species implicated in human and canine leishmaniosis in
      southern Europe. A preliminary study on the prevalence of asymptomatic feline
      leishmaniosis, performed in the areas where the infected cat was identified,
      revealed a low seroprevalence of infection: only 1 (0.9%) of the 110 cat sera
      examined by indirect fluorescent antibody test was positive for anti-Leishmania
      antibodies. Because clinical signs in feline leishmaniosis are unspecific and
      similar to those observed in other diseases commonly found in this species,
      leishmaniosis must be added to the differential diagnosis by feline veterinary
      practitioners and adequate serologic and histopathologic investigations must be
      performed in endemic areas.

PMID- 12062508
TI  - Seroprevalence of Neospora, Toxoplasma gondii and Sarcocystis neurona antibodies
      in horses from Jeju island, South Korea.
AB  - Parasite-specific antibody responses to Neospora spp. and Toxoplasma gondii,
      antigens were detected using the indirect fluorescent antibody test (IFAT) and
      immunoblot analysis in a korean equine population located on Jeju island, South
      Korea (126 degrees 12' E and 33 degrees 34' N). For comparison, a naturally
      infected Neospora hughesi horse and an experimentally inoculated T. gondii equid
      (pony) were used. In addition, all samples were tested for antibodies to
      Sarcocystis neurona by immunoblot analysis. A total of 191 serum samples from
      clinically normal horses were evaluated. Only 2% (4 out of 191) and 2.6% (5 out
      of 191) of the samples had showed reactivity at 1:100 using the IFAT for Neospora
      spp. and T. gondii, respectively. For T. gondii, two samples matched the antigen
      banding pattern of the positive control by immunoblot analysis. No sample was
      positive for N. hughesi by immunoblot analysis in this study. Overall, there was
      a 1% seroprevalence for T. gondii antibodies in the horses tested based on
      immunoblot analysis. The seroprevalence for S. neurona and N. hughesi antibodies
      was 0%. We concluded that these horses are either not routinely exposed to these
      parasites or antibody titers are not sufficiently elevated to be detectable. It
      is most likely the former explanation since Jeju island equine farms are isolated
      from the main land, and the horses were all less than 3 years of age. This naive
      population of horses could be useful when evaluating S. neurona serodiagnostic
      tests or evaluating potential S. neurona vaccines since exposure risks to S.
      neurona and closely related parasites are negligible.

PMID- 12062509
TI  - A survey of Blastocystis sp. in livestock, pets, and zoo animals in Japan.
AB  - The prevalence of Blastocystis sp. was examined in fecal samples collected from
      cattle, pigs, dogs, and a variety of zoo animals (primates, carnivores,
      herbivores, pheasants, and ducks) by direct observation of fresh fecal
      suspensions or cultured materials, using light microscopy. The cattle and pigs
      were randomly sampled from 11 and 12 commercial farms, respectively, located in
      the western region of Japan. The dog material used in this study was obtained
      from pets housed in an animal shelter in the city of Osaka. Zoo animals were
      chosen based on housing conditions that minimized the possibility of intra-zoo
      transmission of the organism. The prevalence rate among the groups varied
      greatly. A high prevalence of infection was observed in the farm animal group,
      ranging from 95% (58/61) in pigs to 71% (39/55) in cattle, whereas the dog fecal
      samples were completely free of the organism. Prevalence of the organism in the
      zoo animal were 85% (29/34) in primates, 80% (8/10) in pheasants, 56% (9/16) in
      ducks, and 0% (0/58) in various carnivores and herbivores. Among the zoo animals
      infected with Blastocystis, eight species of primates, eight species of
      pheasants, and four species of ducks were confirmed as new hosts. Since
      Blastocystis organisms isolated from various animals were morphologically
      indistinguishable from Blastocystis hominis by light microscopy, further genomic
      studies are required for analysis of the zoonotic potential or etiological
      significance of these isolates.

PMID- 12062510
TI  - Protection against and establishment of Dictyocaulus viviparus following primary
      infection at different dose levels.
AB  - In two experiments, calves were primary infected with 1 of 12 (Experiment 1) or 6
      (Experiment 2) different dose levels of Dictyocaulus viviparus infective larvae
      (L3), ranging from 5 to 2000 L3. To study the level of protection induced by the
      primary infection a challenge infection with 2000 L3 was given on day 10
      (Experiment 1) or day 35 (Experiment 2). In both experiments, challenge control
      calves were included. Eleven days later, the challenge calves were necropsied for
      worm counts. Results were compared with predictions from a simulation model.
      Establishment of the primary infection was dose independent, lying on average in
      the range of 20-30%. The ratio female:male worms in the counts from the primary
      or from the challenge infection was consistently close to 1:1 irrespective of
      primary infection dose level or protection having developed in some of the
      calves. Level of early protection (10 days after a primary infection-Experiment
      1) against establishment of the challenge infection depended significantly on
      primary infection dose level (P<0.01). At 10 days, after a primary infection, low
      dose levels did not result in protection against a challenge infection. In
      contrast, similarly low dose levels did result in partial protection, 35 days
      after the primary infection. Results confirmed that our provisional simulation
      model satisfactorily predicts primary infection outcomes, but that it does not
      accurately predict levels of protection and immunity against re-infections.

PMID- 12062511
TI  - Antigen-specific IgG(T) responses in natural and experimental cyathostominae
      infection in horses.
AB  - Equine clinical larval cyathostominosis is caused by simultaneous mass emergence
      of previously inhibited larvae from the mucosa of the colon. Clinical signs
      include diarrhoea, colic, weight loss and malaise, and in up to 50% of cases, the
      disease results in death. Cyathostominae spend a large part of their life cycle
      as larval stages in the intestinal mucosa. Definitive diagnosis is difficult due
      to the lack of diagnostic methods for pre-patent infection. In the present study,
      the enzyme-linked immunosorbent assay (ELISA) was used to investigate isotype
      responses to larval cyathostominae somatic antigen. Measurement of anti-larval
      IgG(T) responses appeared to have the most immunodiagnostic potential. An
      increase in IgG(T) response was detected to crude larval antigen by 5 weeks post
      infection (PI) in individual infected ponies. Subsequently, IgG(T) responses to
      larval and adult somatic extracts were examined by Western blotting using sera
      from experimentally-infected horses and helminth-naive animals (n=6). Two antigen
      complexes, designated A and B, in larval somatic antigen were recognised
      specifically by the infected animals by 7 weeks PI. Sera taken from 23
      endemically-infected animals, whose cyathostominae burdens had been enumerated,
      were also used to identify putative diagnostic antigens. Eighteen horses had
      positive mucosal worm burdens (range 723-3,595,725) and all but two of these
      animals had serum IgG(T) antibody specific to either complex. Moreover, IgG(T)
      responses specific to antigen complexes A and B were absent in all five parasite
      negative horses that were tested. Serum IgG(T) responses to either of the two
      complexes were identified in five clinical cases tested. IgG(T) responses to
      adult antigen somatic extracts were more heterogeneous, with no clear pattern
      between experimentally-infected ponies and helminth-free controls. The results
      indicate that increases in serum IgG(T) to mucosal larvae occur in the pre-patent
      period and that two antigenic complexes within somatic preparations of these
      stages have immunodiagnostic potential.

PMID- 12062512
TI  - Specific polymerase chain reaction for differential diagnosis of Dirofilaria
      immitis and Dipetalonema reconditum using primers derived from internal
      transcribed spacer region 2 (ITS2).
AB  - Both Dirofilaria immiti and Dipetalonema reconditum may be found in blood of
      infected dogs but it is not easy to distinguish D. immitis from D. reconditum in
      morphology. We cloned and sequenced the contiguous internal transcribed spacer
      (ITS) region, ITS1-5.8S-ITS2, of these two different parasites and published on
      GenBank as AF217800 for D. immiti and AF217801 for D. reconditum in this study.
      We designed two pairs of specific primers derived from ITS2 being used for
      polymerase chain reaction (PCR). The amplicons of ITS2 from D. immiti and D.
      reconditum are 302 and 348bp, respectively. Moreover, the limitation for
      amplifying ITS2 gene using this PCR demonstrated that 1 x 10(-2) microfilaria of
      each species of parasite smashed or even with mixed samples could be detected and
      the PCR products were predicted as the same as that described above. Thus, D.
      immiti and D. reconditum could be differentially diagnosed by this specific PCR.
      Seventeen clinical cases were evaluated and all of them were correctly
      identified. In this study, ITS1-5.8S-ITS2 of D. immiti or D. reconditum were the
      first time sequenced and analyzed. No significant similarity of ITS1 and ITS2
      between D. immiti and D. reconditum could be observed.

PMID- 12062513
TI  - Helminth infections in Danish organic swine herds.
AB  - In nine organic swine herds, faecal excretion and pasture contamination by
      parasite eggs/larvae were studied in a period from March to October 1999. It was
      shown that the organic pigs were infected with Ascaris suum (28% of weaners, 33%
      of fatteners, 4% of sows), Trichuris suis (4% of weaners, 13% of fatteners, <1%
      of sows) and Oesophagostomum spp. (5% of weaners, 14% of fatteners, 20% of sows)
      whereas no infections with Hyostrongylus rubidus, Metastrongylus spp. or
      Strongyloides ransomi were detected. Moreover, no pigs showed clinical signs of
      infestations with scabies or lice. In the soil samples, very few Trichuris eggs
      were found throughout the season, whereas Ascaris eggs were found in 14% of the
      soil samples from sow pastures and in 35% from slaughter pig pastures, with the
      first infective eggs being recorded in July and the maximum number in August.
      Infective Oesophagostomum larvae were found in the grass samples in increasing
      numbers from May to October. Single herd cases of exceptionally high parasite
      infection levels are described in relation to herd management procedures.

PMID- 12062514
TI  - Analysis of the 18S rRNA gene sequence of a Hepatozoon detected in two Japanese
      dogs.
AB  - Partial sequences of the 18S rRNA gene (625 bp) from a Hepatozoon detected in two
      canine hepatozoonosis cases, one clinical and one subclinical, in Japan were
      analyzed. Both sequences were identical to each other and they were closely
      related to the Hepatozoon canis strain found in Israel with 99% (617/625)
      nucleotide identity. Both Hepatozoon americanum and Hepatozoon catasbianae were
      distantly related to the Japanese Hepatozoon with 94% (586/625) and 91% (566/625)
      identities, respectively. In a phylogenetic tree, the Japanese Hepatozoon was
      most closely related to H. canis from Israel but was significantly different than
      H. americanum and H. catasbianae. These results suggest that the Hepatozoon
      detected in the Japanese dogs might be a strain variant of H. canis, but is
      apparently a different species than H. americanum.

PMID- 12062515
TI  - The Mycobacterium avium subsp. paratuberculosis ELISA response by parity and
      stage of lactation.
AB  - Two cross-sectional studies were carried out to determine the enzyme-linked
      immunosorbent assay (ELISA) response to Mycobacterium avium subsp.
      paratuberculosis (Map) by cow characteristics and stage of lactation. One of the
      studies (referred to as "milk-group") used milk samples from all lactating cows
      (n=7994) in 108 Danish dairy herds. The other study (referred to as "serum
      group") used serum samples collected from all cows (n=5323) in a subset of 72
      herds from the 108 herds. These samples were analysed using a similar ELISA for
      detection of antibodies. The results from the ELISAs were interpreted with two
      cut-off values as the optimal cut-off value is not known, and as several levels
      are recommended to be used in practice. The results showed that the probability
      of being ELISA-positive was two to three times lower for cows in parity 1
      relative to cows in other parities using both milk and serum ELISA. At the
      beginning of the lactation the probability of being positive was highest in the
      milk ELISA. In the serum ELISA the odds of being positive was highest at the end
      of lactation. The findings are important in the interpretation of ELISA results
      at cow level with a subsequent tentative diagnosis and correction for parity and
      stage of lactation should be considered when providing a diagnosis of
      paratuberculosis. Some issues related to the pathogenesis are also discussed.

PMID- 12062516
TI  - A longitudinal study of Neospora caninum infection on a dairy farm in New
      Zealand.
AB  - A 600-cow New Zealand dairy herd experienced an abortion storm in 1997 and was
      monitored (blood sampling at about 3-month intervals) from May 1997 until January
      1999. Abortion risk reached 9% in 1997 and was highest in heifers at 19%. The
      abortion risk decreased in 1998 to 3.2% (still somewhat higher than during the
      years prior to the outbreak). The serological reaction pattern for Neospora
      caninum showed an association with abortion risk only around the time of the 1997
      outbreak when seropositive cows were 4.2 times more likely to abort than negative
      ones. Over the whole study period, only 27% of cows that were sampled on all nine
      visits always tested negative. Offspring from dams which had positive tests for
      Neospora caninum were 2.4 times more likely to abort than those from dams testing
      consistently negative. Controlling for age and breed, seropositive cows produced
      more milk than those that were consistently negative. Infection might have been
      present endemically within this herd prior to the epidemic, but in 1997 an
      additional factor appeared to have triggered the outbreak.

PMID- 12062517
TI  - Prevalence and risk factors for contamination with Listeria monocytogenes of
      imported and exported meat and fish products in Switzerland, 1992-2000.
AB  - A total of 2053 import and 164 export samples from 425 production plants were
      examined over a 9-year period (1992-2000) for the presence of Listeria
      monocytogenes (L. monocytogenes) in Switzerland. Overall, 282 samples (12.2%) and
      85 plants (20.5%) harbored the pathogen. The highest isolation risk was for
      marinated fish (38%); the lowest was in cured- and dried-meat products.
      Unconditional fixed-effect logistic regression was used to identify the main
      hazards associated with the presence of L. monocytogenes. The plant-level model
      considered potential risk factors for a positive culture operating at the
      production-plant level by including a random effect of plant and year. Food
      category was the only significant factor; sampling site, country of origin and
      season were not significant. Marinated fish was a strong predictor for positive
      culture, whereas cooked- and cured-meat products were protective. Plant and year
      effects were significant. Control measures should be focused on specific food
      items in each production plant.

PMID- 12062518
TI  - Use of variograms to detect critical spatial distances for the Knox's test.
AB  - We aimed to find critical spatial distances (as an input quantity for the Knox's
      test) using geostatistical methods. The spatiotemporal data set included all
      individual-chamois cases of scabies observed in Styrian chamois populations in
      137 of 2837 game preserves in Styria (a province in the south of Austria) over
      the time period between 1952 and 1998. Theoretical variogram models were fitted
      to empirical variograms, which were calculated for cycles of 5 years. The unit of
      analysis was the mean quadratic deviation between individual-chamois cases of
      scabies. The "range" (which represents the transition from the state in which
      spatial correlation exists to the state in which there is absence of spatial
      correlation) was used as an indicator for the critical spatial distance for the
      Knox's test. The critical distances for the 5-year cycles varied between 10.8 and
      16.0 km. If the time of observation is not considered, the critical "overall"
      distance amounted to 13.5 km.

PMID- 12062519
TI  - Epidemiology of Mycobacterium bovis in free-ranging white-tailed deer, Michigan,
      USA, 1995-2000.
AB  - An endemic area of bovine tuberculosis (TB) (Mycobacterium bovis) currently
      affecting wild white-tailed deer (Odocoileus virginianus) in northern lower
      Michigan, USA, constitutes the first self-sustaining outbreak of the infection in
      free-ranging North American cervids. Given this precedent, epidemiologic insights
      gained from the outbreak afford the opportunity to guide not only current
      surveillance and intervention but also control efforts for future outbreaks
      involving wildlife reservoirs. Our specific objectives were to evaluate
      retrospective data from field surveillance conducted from 1995 to 2000 to
      determine apparent prevalence, trends in apparent prevalence, and the effects of
      various factors on the odds of being M. bovis positive. Data were gathered from
      post-mortem examinations of 62,560 wild deer collected from all 83 Michigan
      counties. Records of survey method, sex, age, geographic area and infection
      status as determined by mycobacterial culture were subjected to trend analysis
      and multivariable logistic regression. Apparent prevalence for the period was
      0.54% (336/62,560) statewide. Prevalence varied widely with geographic area, but
      significantly decreased since 1995 in the core area of the outbreak-which
      coincided with implementation of control strategies. Significant risk factors
      were geographic area, sex, age, and the sex-by-age interaction. The survey method
      by which deer were obtained for testing was not a predictor of infection. Our
      results to date suggest an outbreak characterized by broad areas of very low
      prevalence surrounding focal areas where prevalence is sometimes orders-of
      magnitude higher (e.g., deer originating from the core area were up to 147 times
      more likely to be TB positive than deer from other areas). Our results also
      identify older male deer as most likely to be M. bovis positive (OR=11.3, 95% CI
      3.2, 40.3 for bucks > or =5 years vs. does < or =1.5 years)-an observation
      consistent with the biology and behavior of the species. Synthesizing these
      results with those of other ongoing investigations, we hypothesize a two-stage
      model of disease transmission where TB is maintained at very low prevalence in
      matriarchal groups, with primary dissemination of the disease attributable to the
      dispersal and movements of bucks (as well as to the large aggregations of animals
      created by human activities).

PMID- 12062520
TI  - Clinical bovine mastitis in Norway.
AB  - A brief description of the Norwegian Health Card System for Cattle (NHCSC) is
      given. The incidence of clinical mastitis (CM) for dairy cows in Norway was
      determined using NHCSC data recorded from 1992 to 1995. Incidence density (ID)
      (which included repeated episodes of CM in the same cow) and various measures of
      risk were estimated. The ID for the entire study period, comprising almost 1.2
      million cow-years, was 49 CM episodes per 100 cow-years at risk. Twenty-six
      percent of the cows with CM experienced at least two episodes of CM in 1 year.
      For the entire study period (1992-1995), the ID was 30 episodes per 100 cow-years
      at risk for acute CM (ACM). Annual risk of CM for fixed cohorts of cows that were
      at risk 1 January the particular year, as estimated by the actuarial method and
      accounting for the exact time of removal of culled cows, varied between 0.32
      (1992) and 0.35 (1994 and 1995). Numerically similar risk estimates were found
      when using the density method for fixed cohorts. Lactational incidence risk for
      cows that calved in 1992-1994 varied between 0.32 and 0.34. In herds of a size
      greater than five cow-years, the crude ID of CM tended to decrease with
      increasing herd size. The ID of CM varied considerably between counties, and was
      higher in coastal areas than in inland areas.

PMID- 12062521
TI  - Ethnoveterinary medical practice for ruminants in the subhumid zone of northern
      Nigeria.
AB  - Ethnoveterinary medical practice is widespread among herdsmen and village
      livestock producers in northern Nigeria where livestock in the country are
      concentrated. For most of these livestock owners, modern veterinary inputs and
      services are not readily available and are relatively expensive. Traditional
      remedies are locally available and cheaper. Our questioning of 50 herdsmen and
      village livestock producers revealed that the ingredients used in these
      indigenous practices include plant extracts, seeds, leaves, barks of trees,
      tubers and roots of various plants. These are processed in various ways and
      administered to animals for a variety of disease conditions. More recently used
      ingredients include kerosene and spent engine oil. Considering the combination of
      ingredients used by the traditional animal-health practitioners, it is likely
      that additive, synergistic and nutritional effects might be involved in
      alleviating the problem of ill-health in animals. Herdsmen and livestock owners
      readily identify signs of disease (although some common infectious diseases have
      several signs and may affect various parts of the animal body). Aspects of
      indigenous health care practices are contrasted with modern veterinary health
      care.

PMID- 12062522
TI  - Synthesis of glucopyranoside-based ligands for D-myo-inositol 1,4,5-trisphosphate
      receptors.
AB  - Adenophostins A and B are naturally occurring glyconucleotides that interact
      potently with receptors for D-myo-inositol 1,4,5-trisphosphate, an important
      second messenger molecule in most cell types. Here we describe the design and
      synthesis of glucopyranoside-based analogues of adenophostin A lacking the
      adenine component. The key synthetic strategy involves glycosylation of
      selectively protected alcohols, derived from methyl beta-D-ribofuranoside or 1,4
      anhydroerythritol, using glycosyl donors synthesised from 2,6-di-O-benzyl-D
      glucopyranose derivatives. Further elaboration and deprotection of the coupled
      products gave two trisphosphate analogues; methyl 3-O-alpha-D-glucopyranosyl-beta
      D-ribofuranoside 2,3',4'-trisphosphate ("ribophostin") and (3'S,4'R)-3'
      hydroxytetrahydrofuran-4'-yl alpha-D-glucopyranoside 3,4,3'-trisphosphosphate
      ("furanophostin"). The route to furanophostin was further modified to give
      (3'S,4'R)-3'-hydroxytetrahydrofuran-4'-yl alpha-D-glucopyranoside 3'-phosphate
      3,4-bisphosphorothioate, the first phosphorothioate-containing adenophostin
      analogue.

PMID- 12062523
TI  - Synthesis of 1-deoxy-L-gulonojirimycin (L-guloDNJ) and 1-deoxy-D-talonojirimycin
      (D-taloDNJ).
AB  - Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5
      dideoxy-1,5-imino-L-gulitol (L-guloDNJ) and 1,5-dideoxy-1,5-imino-L-talitol (L
      taloDNJ) are reported, from D-mannose and D-fructose, respectively. The key steps
      in both syntheses involved reductive aminative cyclizations. Thus, L-guloDNJ was
      obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl-D
      mannononitrile with LiAlH(4) in DME to give the protected azasugar which upon
      hydrolysis with HCl afforded crystalline L-guloDNJ as the HCl salt in 29% overall
      yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-beta
      D-ribohexulofuranose obtained from D-fructose in six steps, followed by treatment
      with HCl, afforded L-taloDNJ as an HCl salt in approximately 10% overall yield.

PMID- 12062524
TI  - Synthesis of dimeric lactose and dimeric (sialyl) Lewis(X) glycolipids.
AB  - To investigate structural requirements for the homophilic interaction between
      carbohydrates on planar model membranes, divalent derivatives with enforced
      proximity between the two carbohydrate epitopes (lactose, Lewis(X), and sialyl
      Lewis(X)) were synthesized by use of a dimeric membrane anchor as scaffold.

PMID- 12062525
TI  - Synthesis and utility of sulfated chromogenic carbohydrate model substrates for
      measuring activities of mucin-desulfating enzymes.
AB  - A chromogenic substrate, 4-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside
      6-sodium sulfate was synthesized and used in combination with beta-N
      acetylhexosaminidase for detection of the sulfatase, MdsA, by release of 4
      nitrophenol. MdsA was originally isolated from the bacterium Prevotella strain
      RS2 and is believed to be involved in desulfation of sulfomucins, major
      components of the mucus barrier protecting the human colon surface. The exo
      nature of the MdsA sulfatase was indicated by its inability to de-esterify the
      disaccharide 4-nitrophenyl beta-D-galactopyranosyl-(1-->4)-2-acetamido-2-deoxy
      beta-D-glucopyranoside 6-sodium sulfate. This latter compound was prepared from
      monosaccharide precursors by two different methods, the shorter requiring just
      six steps from 4-nitrophenyl 2-acetamido-2-deoxy-beta-D-glucopyranoside and
      giving an overall yield of 26.4%. The syntheses of 4-nitrophenyl beta-D
      galactopyranoside 3-triethylammonium sulfate and 6-triethylammonium sulfate and
      their use in combination with beta-galactosidase as chromogenic substrates for
      detecting Bacteroides fragilis sulfatases with different specificities was also
      demonstrated.

PMID- 12062526
TI  - Reactions of alpha amylases with starch granules in aqueous suspension giving
      products in solution and in a minimum amount of water giving products inside the
      granule.
AB  - Porcine pancreatic alpha amylase (PPA) and Bacillus amyloliquefaciens alpha
      amylase (BAA) were allowed to react with starch granules from maize, waxy maize,
      amylomaize-7, and potato in an aqueous suspension with a starch to water ratio of
      1:10 and in a minimum of water with a starch to water ratio of 1:1. Quantitative
      amounts of the maltodextrin products were determined by TLC and scanning
      densitometry. The two alpha amylases gave different products that were
      characteristic of their unique action patterns. The percent conversion differed
      for the different kinds of starches and for the two kinds of reaction conditions.
      Maize and waxy maize starches were converted into about twice as much
      maltodextrins than were amylomaize-7 and potato starches by both enzymes and
      under both reaction conditions. The aqueous suspension gave much greater
      conversion into maltodextrins than did the minimum water condition. BAA gave 3
      14% greater conversion of the granules into maltodextrins than did PPA, with the
      exception of potato starch.

PMID- 12062527
TI  - Structure of the phenol-soluble polysaccharide from Shewanella putrefaciens
      strain A6.
AB  - The structure of the phenol-soluble polysaccharide from Shewanella putrefaciens
      strain A6 has been elucidated. Chemical modifications of the polymer in
      conjunction with 1H and 13C NMR spectroscopy, including 2D techniques, were
      employed in the analysis. It is concluded that the repeating unit is composed of
      two nine-carbon sugars as follows: -->4)-alpha-NonpA-(2-->3)-beta-Sugp-(1-->
      where alpha-NonpA is 5-acetamido-7-acetamidino-8-O-acetyl-3,5,7,9-tetradeoxy-L
      glycero-alpha-D-galacto-non-2-ulosonic acid (8eLeg) and beta-Sugp is 2-acetamido
      2,6-dideoxy-4-C-(3'-carboxamide-2',2'-dihydroxypropyl)-beta-D-galactopyranose,
      with the proposed name Shewanellose (She).

PMID- 12062528
TI  - Non-covalent associations of cyclomaltooligosaccharides (cyclodextrins) with
      carotenoids in water. A study on the alpha- and beta-cyclodextrin/psi,psi
      carotene (lycopene) systems by light scattering, ionspray ionization and tandem
      mass spectrometry.
AB  - Water-soluble complexes of the dietary carotenoid psi,psi-carotene (lycopene 1)
      with cyclomaltohexaose (alpha-cyclodextrin, alphaCD) and cyclomaltoheptaose (beta
      cyclodextrin, betaCD) have been prepared and characterized via multiangle light
      scattering (MALS), ionspray/electrospray ionization (IS/ESI) mass spectrometry
      (MS) and tandem MS. MALS experiments point out that large aggregates of
      particles, on the nanometer-size scale, are present in water, with meaningful
      differences in the shape of the alphaCD/1 aggregates with respect to betaCD/1
      analogues. The true 1:1 alphaCD/1 inclusion complex has been observed by IS/ESIMS
      and confirmed by tandem MS. The structure of CD/1 aggregations in water is
      proposed which are consistent with the combined MALS and MS experimental results.

PMID- 12062529
TI  - The structure of a galactan sulfate from the red seaweed Bostrychia montagnei.
AB  - The sulfated, methylated galactan isolated from the red seaweed Bostrychia
      montagnei, showed an unusually narrow structural dispersion. This agaran has the
      defining linear backbone of alternating 3-linked beta-D-galactopyranosyl units
      and 4-linked alpha-L-galactopyranosyl and 3,6-anhydrogalactopyranosyl residues.
      The D-units have C-6 methylation, C-6 single stubs of xylopyranosyl and minor to
      trace amounts of (possible) C-6 linked single stubs of galactopyranosyl. These
      units are mainly sulfated on C-4 with lesser sulfation at C-6 and minor at C-2.
      The L-residues are mainly methylated on C-2 of the 3,6-anhydrogalactopyranosyl
      and sulfated on C-3 of the L-galactopyranosyl; minor amounts of 2,3- and 3,6
      disulfated and 2-O-methyl or 2-O-glycosyl 3-sulfated L-galactopyranosyl were also
      found.

PMID- 12062532
TI  - Transscleral drug delivery to the retina and choroid.
AB  - Rapid advances in the molecular pathogenesis of retinal and choroidal disorders
      have highlighted the urgent need for innovative drug delivery modalities to the
      loci of pathology. In vitro and in vivo studies suggest that the transscleral
      route may offer a means to achieve the goal of sustained, targeted drug delivery
      to the posterior segment. Potentially therapeutic concentrations of
      macromolecules with retention of bioactivity can be attained in the choroid and
      retina via minimally invasive transscleral delivery.

PMID- 12062530
TI  - Molecular interactions in bacterial cellulose composites studied by 1D FT-IR and
      dynamic 2D FT-IR spectroscopy.
AB  - Specific strain-induced orientation and interactions in three Acetobacter
      cellulose composites: cellulose (C), cellulose/pectin (CP) and
      cellulose/xyloglucan (CXG) were characterized by FT-IR and dynamic 2D FT-IR
      spectroscopies. On the molecular level, the reorientation of the cellulose
      fibrils occurred in the direction of the applied mechanical strain. The cellulose
      network reorientation depends on the composition of the matrix, including the
      water content, which lubricates the motion of macromolecules in the network. At
      the submolecular level, dynamic 2D FT-IR data suggested that there was no
      interaction between cellulose and pectin in CP and that they responded
      independently to a small amplitude strain, while in CXG, cellulose and xyloglucan
      were uniformly strained along the sample length.

PMID- 12062533
TI  - The role of tangential dispersion in retinal mosaic formation.
AB  - Individual types of retinal nerve cell are spaced across the retina in an orderly
      manner, ensuring a uniform sampling of the visual field. This regularity in
      cellular spacing has been commonly attributed to fate determination mechanisms
      operating around the time of cell birth, an hypothesis presuming that the
      position of a nerve cell is fixed within the plane of the retina from the time of
      its determination. At odds with this view, recent results from X-inactivation
      mosaic mice indicate that certain classes of retinal nerve cell, those known to
      form orderly mosaics in the adult retina, disperse tangentially during
      development. Furthermore, studies defining the spatial characteristics of
      developing and mature retinal mosaics suggest that cell-cell interactions around
      the time of morphological differentiation lead to mutual repulsion. Modelling
      studies in turn show that nothing more than a simple minimal spacing rule between
      neighboring cells of the same type is sufficient for the creation of the global
      patterning observed in biological retinal mosaics. For some cell types, the size
      of this "exclusion zone" surrounding individual cells is shown to be an intrinsic
      characteristic of each cell type, invariant across the retina, and accounting for
      the variation in mosaic regularity across changes in cell density. These results
      show how short-distance movements driven by intercellular interactions at the
      local level may mediate the emergence of the global patterning characteristic of
      retinal mosaics during development.

PMID- 12062534
TI  - Ocular lipid deposition and hyperlipoproteinaemia.
AB  - In all species there are potential ocular manifestations when circulating
      lipoproteins are raised and these may be transient or permanent Many factors,
      both systemic and local, influence lipid influx and accumulation (progression)
      and lipid mobilisation and efflux (regression). In both humans and animals some
      types of lipid deposition will regress if the local and systemic factors involved
      in pathogenesis can be modified. There are inescapable parallels with the same
      phenomena in other tissues.Three types of corneal lipid deposition have been
      linked with hyperlipoproteinaemia. In corneal arcus, lipid is deposited
      preferentially in the warmest part of the cornea initially and, in people, the
      lipid remains almost exclusively extracellular. In animals, corneal arcus is
      associated with initial extracellular lipid deposition followed by the appearance
      of intracellular lipid and vascularisation, so that established corneal arcus
      tends to become more typical of lipid keratopathy. In humans,
      hyperlipoproteinaemia may be an associated systemic factor and early onset
      corneal arcus is a recognised feature of certain primary hyperlipoproteinaemias
      and their secondary phenotypes. In dogs, corneal arcus is always associated with
      hyperlipoproteinaemia. Corneal vascularisation is a ubiquitous feature of lipid
      keratopathy in all species and both necrotic fibroblasts and foam cells are
      common in progressive lesions. The extent and position of lipid deposition and
      the evolution of lipid keratopathy can be related to local ocular disease and
      circulating lipids and lipoproteins. Many aspects of the pathogenesis of lipid
      keratopathy are similar to those of atherogenesis. Hyperlipoproteinaemia,
      especially hypercholesterolaemia is the commonest systemic abnormality. In
      crystalline stromal dystrophy (Schnyder's crystalline stromal dystrophy) of the
      cornea there is no inflammatory element and no vascularisation. The dystrophy is
      associated with accumulation of lipid within the corneal fibroblasts, but typical
      foam cells are absent, the crystalline opacity involves the coolest part of the
      cornea, correlates with local fibroblast death, and is always bilateral.
      Hyperlipoproteinaemia, may be present, but this is not universally so.The
      objective of this paper is to evaluate the factors that may influence ocular
      involvement in hyperlipoproteinaemia. A comparative approach, utilising
      information available from studies of both ocular and non-ocular tissues, aids
      elucidation of the complex pathogenesis.

PMID- 12062535
TI  - Macular pigment: influences on visual acuity and visibility.
AB  - There is increasing evidence that the macular pigment (MP) carotenoids lutein (L)
      and zeaxanthin (Z) protect the retina and lens from age-related loss. As a
      result, the use of L and Z supplements has increased dramatically in recent
      years. An increasing number of reports have suggested that L and Z
      supplementation (and increased MP density) are related to improved visual
      performance in normal subjects and patients with retinal and lenticular disease.
      These improvements in vision could be due either to changes in the underlying
      biology and/or optical changes. The optical mechanisms, i.e., preferential
      absorption of short-wave light, underlying these putative improvements in vision,
      however, have not been properly evaluated. Two major hypotheses are discussed.
      The acuity hypothesis posits that MP could improve visual function by reducing
      the effects of chromatic aberration. The visibility hypothesis is based on the
      idea that MP may improve vision through the atmosphere by preferentially
      absorbing blue haze (short-wave dominant air light that produces a veiling
      luminance when viewing objects at a distance).

PMID- 12062536
TI  - Intermediate-filament expression in ocular tissue.
AB  - Intermediate-filament proteins (IFPs) occur in the intracellular cytoskeleton of
      eukaryotic cells, and their expression in diverse tissues is related both to
      embryology as well as to differentiation. Although the available information
      concerning their functional properties in vivo is still incomplete, antibodies
      against individual IFPs are commonly used in immunohistochemical procedures as
      markers for differentiation, and these antibodies are of outstanding value in the
      routine histopathological evaluation of tumor specimens. This review presents a
      compilation of the currently available data concerning IFP expression in normal
      and diseased ocular tissues. Representatives of every known class of IFP have
      been detected in normal ocular tissues. The external epithelia exhibit complex
      expression patterns of cytokeratin (CK) polypeptides, with CK3 and CK12 being
      specific markers of the corneal epithelium. Recent research has revealed that
      single mutant CK polypeptides may play a role in the pathogenesis of corneal
      dystrophies. The internal ocular epithelia reveal simple but specific patterns of
      IFP expression, these comprising simple-epithelial CKs and/or the mesenchymal
      IFP, vimentin. The IFP complement of the neuronal structures of the eye embraces
      several distinct IFP classes and reflects the diversity of the cell types present
      at these sites. With respect to ocular tumors, the IFP profile of melanomas might
      be correlated with metastatic potential. In conclusion, IFP analysis may be able
      to cast light on the pathogenesis of ocular diseases, as well as being a valuable
      adjunct in ophthalmopathological diagnosis.

PMID- 12062537
TI  - Prophylaxis of venous thromboembolism with subcutaneous melagatran in total hip
      or total knee replacement: results from Phase II studies.
AB  - The first clinical studies evaluating the safety and efficacy of melagatran, a
      novel, direct thrombin inhibitor, given subcutaneously as prophylaxis for venous
      thromboembolism (VTE) following total hip (THR) or total knee replacement (TKR)
      are reported. In Study I, 66 patients received subcutaneous melagatran (1.5-6 mg
      bid) in a poloxamer depot formulation, and in Study II, 104 patients received
      subcutaneous melagatran (2-4 mg bid) in saline or as a depot formulation in
      cyclodextrin. Treatment was given for 8-11 days, with the first dose administered
      immediately before surgery. Deep vein thrombosis (DVT) was assessed using
      mandatory bilateral venography on the last day of treatment, and pulmonary
      scintigraphy was performed if required. Bleeding complications occurred in the
      only patient who received melagatran 6 mg, and this dose-arm was discontinued.
      The frequency of VTE was low (12/129=9%, 95% confidence interval [CI]: 5-16%).
      Eight patients (6%) had distal DVT, three (2%) had proximal DVT, and in one
      patient (1%) pulmonary embolism (PE) was verified. In conclusion, subcutaneous
      melagatran 1.5-4.5 mg bid in saline or depot formulation was well tolerated and
      resulted in a low frequency of VTE.

PMID- 12062538
TI  - Markers of inflammation and hypercoagulability in diabetic and nondiabetic
      patients with lower extremity ischemia.
AB  - Lower extremity ischemia is one aspect of atherosclerosis, a disease associated
      with both inflammation and hypercoagulability. Many recent studies have focused
      on a diversity of mechanisms by which inflammation can promote blood clotting.
      However, it has not been proven that inflammation can actually trigger clinically
      relevant thrombus formation in vivo. The purpose of the study was to determine
      the plasma levels of markers of inflammation and their possible association with
      markers for coagulability with special emphasis on the difference between
      patients with and without diabetes. Forty-six patients, 20 diabetics and 26
      without diabetes scheduled for lower extremity revascularisation were examined by
      preoperative blood sampling. A strong positive correlation between C-reactive
      protein (CRP) and fibrinogen was found, particularly in diabetics. A high
      fibrinogen level was not associated with other markers of hypercoagulability,
      Thrombin-Antithrombin (TAT), Prothrombin Fragment 1+2 (F 1+2) and D-dimer
      although the latter three correlated with each other. There was also a
      correlation between von Willebrand antigen (vWF) and CRP, also in this case the
      relationship was dependent on the findings in patients with diabetes. It is
      concluded that there is a difference between diabetic and nondiabetic patients
      with lower limb ischemia with the former showing stronger signs of inflammation.

PMID- 12062539
TI  - High-dose aspirin in addition to daily low-dose aspirin decreases platelet
      activation in patients before and after percutaneous coronary intervention.
AB  - BACKGROUND: Activated platelets play a major role in acute vessel closure after
      coronary angioplasty. Although aspirin is the routine therapy during angioplasty,
      it only incompletely prevents acute closure. This might be due to suboptimal
      dosing. OBJECTIVE: First, to study the effect of additional high-dose aspirin on
      platelet activation during coronary angioplasty. Second, to assess the potential
      of the new PFA-100 analyzer to evaluate the effect of different doses of aspirin
      in patients undergoing angioplasty. METHODS: Fifty-one patients on 100 mg
      aspirin/day for at least 1 month were randomized to continuation of 100 mg
      aspirin/day only (Group A=24 patients), or to this regime plus a bolus of 1000 mg
      of aspirin given 1 day before angioplasty (Group B=27 patients). Results were
      compared with 15 controls. Platelet function was measured before angioplasty by
      the PFA-100 analyzer; platelet activation was measured by flow cytometry just
      before and 1 h after angioplasty. RESULTS: At baseline, Group A had significantly
      more activated platelets than the control group (P<.001). High-dose aspirin in
      Group B resulted in significantly lower platelet activation as compared with both
      controls (P<.001) and Group A (P<.001). During angioplasty, the number of
      activated platelets decreased significantly in Group A (P<.001), while there was
      no change in Group B (P=.6). The PFA-100 analyzer was unable to detect
      differences between the two treatment groups. CONCLUSIONS: The addition of high
      dose aspirin to daily low-dose aspirin, 1 day before coronary angioplasty,
      significantly reduced the platelet activation state before and after
      intervention. The PFA-100 analyzer did not detect differences in the effect of
      low- versus high-dose aspirin on platelet function.

PMID- 12062540
TI  - Effectiveness of alternative treatments for reducing potential viral contaminants
      from plasma-derived products.
AB  - An issue of great importance and continuing concern with regard to all products
      derived from human plasma is their safety from potential contaminants in the
      source material from which they are purified. Since viral contaminants are a
      major safety consideration with these products, a number of different methods,
      including dry heating, vapor heating, filtration and nanofiltration, ultraviolet
      and gamma irradiation, pasteurization, solvent/detergent (S/D) treatment, sodium
      thiocyanate treatment, and chromatography (immunoaffinity, metal chelation,
      affinity, and ion exchange), have been developed to remove or inactivate
      potentially contaminating viruses. Pasteurization and S/D treatment have emerged
      as the dominant viral inactivation methods. Results summarized in this review
      demonstrate that pasteurization is the broadest and most rigorous currently
      available method for removal of potential viral contaminants from plasma-derived
      products. S/D treatment requires control over a large number of manufacturing
      parameters and has no ability to inactivate nonlipid-enveloped viruses.
      Pasteurization requires control over only a small number of manufacturing
      variables, is easily monitored, and remains effective even if deviations are
      encountered from specified protein and stabilizer concentrations and temperature.
      In addition, pasteurization is effective against a wide range of lipid- and
      nonlipid-enveloped viruses.

PMID- 12062541
TI  - Argatroban therapy does not generate antibodies that alter its anticoagulant
      activity in patients with heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is an immune-mediated syndrome that can
      lead to limb- and life-threatening thrombosis. Argatroban, a small synthetic
      molecule (Argatroban; GlaxoSmithKline, Philadelphia, PA), and lepirudin, a
      protein of non-human origin (Refludan; Aventis, Bridgewater, NJ), are direct
      thrombin inhibitors that have been used successfully for anticoagulant therapy in
      HIT patients. It has been reported that between 44-74% of lepirudin-treated HIT
      patients develop drug-specific antibodies that either enhance or suppress the
      anticoagulant activity of lepirudin. By contrast, there have been no reported
      patient experiences suggestive of unexpected loss or enhancement of argatroban's
      anticoagulant effect in clinical trials, including those in HIT patients, or in
      postmarketing safety surveillance of over 4,800 patients treated in Japan. To
      confirm the lack of antibodies in argatroban-treated patients with HIT, we
      examined plasma for anticoagulant-altering activity and reviewed dosing patterns
      of re-exposed patients. Paired, pre-therapy and post-therapy (> or =7 days)
      plasma pools exhibited comparable in vitro anticoagulant responses (aPTT and
      antithrombin activity) to argatroban supplementation. Argatroban at 5 microg/mL
      similarly prolonged aPTTs of normal plasma pretreated with IgG isolated from pre
      therapy versus post-therapy plasma (P>0.6). In trials, mean argatroban doses
      during initial therapy versus re-exposure were not different among individuals
      anticoagulated for the treatment or prophylaxis of thrombosis (P=0.60) or during
      percutaneous coronary interventions (P=0.79), with no discernable pattern of
      suppression or enhancement of argatroban anticoagulation. Consistent with the
      lack of reported patient experiences suggestive of unexpected loss or enhancement
      of argatroban's anticoagulant effect across clinical trials and post-marketing
      safety surveillance, these data support the lack of anti-argatroban antibodies
      that affect drug activity in argatroban-treated HIT patients.

PMID- 12062542
TI  - Measuring the degree of plasma contact activation induced by artificial
      materials.

PMID- 12062543
TI  - Do clinically relevant circulating concentrations of radiographic contrast agents
      inhibit platelet-dependent arterial thrombosis?
AB  - OBJECTIVES: The purpose of this study was to determine if radiographic contrast
      agents (RCAs) inhibit thrombosis in a rat carotid artery injury model.
      BACKGROUND: Whether ionic and nonionic RCAs differentially affect thrombus
      formation during coronary artery angioplasty is controversial. Although there are
      numerous in vitro studies and clinical trials addressing this issue, it is
      unknown whether clinically relevant plasma concentrations of RCA inhibit platelet
      dependent thrombosis after injury of medium-sized arteries. METHODS: Rats
      received RCA or control solution by bolus (0.7 ml/kg) and constant (0.04
      ml/kg/min) intravenous infusion. Carotid arteries were injured with ferric
      chloride. Blood flow was monitored for 1 h. In vitro platelet aggregation and
      plasma clotting were studied. RESULTS: After injury, mean times free from
      formation of an occlusive, platelet-rich thrombus were 16.2+/-2.3, 49.6+/-18.9,
      47.9+/-21.0, and 37.1+/-22.8 min for rats (n=5/group) that received saline,
      diatrizoate (P<.002 vs. saline), ioxaglate (P<.002 vs. saline), and iohexol
      (P=.06 vs. saline), respectively. Reperfusion after initial occlusion did not
      occur in saline-treated animals, but was common in rats that received RCA. The
      antithrombotic properties of RCA were not explained by their high osmolarities or
      by detectable effects on in vitro platelet aggregation and plasma clotting.
      Plasma concentrations of RCA were <1%. CONCLUSIONS: Systemic administration of
      RCA at doses that achieve low, clinically relevant plasma concentrations can
      inhibit platelet-rich thrombus formation after arterial injury. Antithrombotic
      properties of ionic RCA appear to be greater than those of nonionic RCA.

PMID- 12062544
TI  - Fibrinogen in rat gastrointestinal lymph before, during and after intraduodenal
      administration of emulsified triglyceride: fibrinogen bound to chylomicrons in
      gastrointestinal lymph is functional.
AB  - Samples of gastrointestinal lymph were collected from fasted, male, Sprague
      Dawley rats before, during and after intraduodenal administration of either a
      phospholipid-stabilized, triglyceride-rich emulsion or the dextrose-saline
      diluent of the emulsion. In lipid-treated rats, the triglyceride, total protein,
      and functional fibrinogen contents of lymph increased significantly during the 4
      h of continuous lipid infusion, with all analytes returning to near baseline
      values by 20 h later. Levels of the same analytes changed little, if at all, in
      control animals. As assessed using immunoblotting, chylomicrons in
      gastrointestinal lymph are coated with fibrinogen. Fibrinogen-coated chylomicrons
      readily incorporate into solution phase clots and, in the presence of thrombin,
      adhere in heparin-preventable fashion to each other and to other fibrinogen
      coated surfaces. Taken together, these data indicate that lipid feeding creates
      in gastrointestinal lymph a condition that is conducive temporally to the
      physical association of fibrinogen with newly ingested lipids before they reach
      the circulatory system.

PMID- 12062546
TI  - Effect of low-molecular weight dextran sulfate on coagulation and platelet
      function tests.
AB  - Low-molecular weight dextran sulfate (DXS 5000, M(r) 5 kDa) was found to control
      selectively complement activation without affecting contact activation. However,
      DXS 5000 being a glycosaminoglycan (GAG) may inhibit coagulation, which might
      bear the risk of bleeding complications and limit its clinical use. We
      investigated the influence of DXS 5000 on the prothrombin time (PT), the
      activated partial thromboplastin time (aPTT), the thrombin time (TT), the
      inhibitory capacity of human plasma against activated factor X (FXa), and on
      platelet function as assessed by the platelet function analyzer (PFA-100) and by
      platelet aggregation studies. The PT steadily increased with increasing DXS 5000
      concentration, whereas the aPTT was already prolonged (>300 s) at low DXS 5000
      concentrations (100 microg/ml). The TT was >120 s at DXS 5000 concentrations of
      1000 microg/ml. The inhibitory capacity of human plasma against FXa was dose
      dependently increased by DXS 5000. With increasing DXS 5000 concentrations, a
      prolonged PFA-100 closure time (CT) was observed. Detailed aggregation studies
      revealed a dose-dependent inhibition of platelet aggregation with ristocetin by
      DXS 5000, whereas aggregation with ADP, collagen, and arachidonate was
      unaffected. DXS 5000 induces a disturbance of primary and secondary hemostasis.

PMID- 12062545
TI  - Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by
      inhibiting the anticoagulant protein C/protein S system in cord and adult plasma.
AB  - Protein S (PS) is a vitamin K-dependent plasma protein and serves as a cofactor
      for the anticoagulant activities of activated protein C (APC). We investigated
      the effects of different PS concentrations on prothrombin activation and thrombin
      generation in cord and adult plasma containing APC and different amounts of alpha
      2-macroglobulin (a2-M). Prothrombin activation was assessed by monitoring the
      time-course of prothrombin fragment 1+2 (F1+2) generation. Thrombin generation
      curves were determined by means of a subsampling technique using the chromogenic
      substrate S-2238. We demonstrate a dose-dependent inhibition of the anticoagulant
      action of PS by a2-M: suppression of F1+2 and thrombin generation due to addition
      of PS was stronger in plasma containing low amounts of a2-M than in plasma with
      elevated a2-M levels. Since no complex formation between a2-M and PS was observed
      by means of SDS-PAGE, we attribute decreased anticoagulant action of PS at high
      a2-M levels to enhanced complex formation between APC and a2-M. Thereby, APC is
      subtracted from its cofactor PS, resulting in suppressed formation of the
      anticoagulant APC/PS complex. Thus, our data suggest that a2-M, besides its well
      known anticoagulant effects, also acts as a procoagulant by suppressing the
      formation of the anticoagulant APC/PS complex. Our findings have implications
      particularly on thrombin generation and inhibition in cord plasma, since a2-M
      levels in newborns are elevated over adult values and the antithrombotic APC/PS
      pathway is up-regulated at birth. Therefore, elevated levels of a2-M might
      restrict the up-regulation of the APC/PS pathway.

PMID- 12062547
TI  - The blood-brain barrier accessibility of a heparin-derived oligosaccharides C3.
AB  - Although heparin-derived oligosaccharide(s) (HDO) have been clinically used for
      the management of neurological disorders, such as stroke and Alzheimer's disease
      (AD), very little information on the mechanism of their therapeutic action is
      known. To test the hypothesis that HDO may pass through the blood-brain barrier
      (BBB) to mediate their effects, a pharmacodynamic (PD) model was developed and
      the presence of HDO in the cerebrospinal fluid (CSF) was used as a BBB
      accessibility index. Rats were treated with an ultralow molecular weight (MW)
      heparin fragment C3 via the intravenous or subcutaneous routes at 5-10 mg/kg. At
      varying periods, the plasma, CSF, and brain samples were collected, and
      functional anti-factor Xa activities were measured to quantitate the CSF/plasma
      ratios (CPR) and the brain uptake. C3 showed CPR of 1.7% and 0.8% after
      intravenous and subcutaneous injections, respectively. These findings were
      verified by intravenous administration of tritium-labeled C3 followed by
      detection of the radioactivity in the CSF and brain homogenates. These data
      suggest that ultralow MW HDO may pass through the BBB.

PMID- 12062548
TI  - Pharmacodynamics of the anticoagulant activity (APTT) of an algal polysaccharide.

PMID- 12062549
TI  - First detection of the microsporidium Enterocytozoon bieneusi in non-mammalian
      hosts (chickens).
AB  - Faecal samples taken from eight underweight, approximately 5-week-old broiler
      chickens in a poultry abattoir were investigated for microsporidial infections by
      light microscopy, electron microscopy, and PCR. In two of six chickens, which
      were suspected of being infected with microsporidia by light microscopy,
      Enterocytozoon bieneusi (genotype 'J') was detected by PCR and DNA sequencing,
      and in one of the two PCR-positive samples by extensive electron microscopy. This
      is the first time that E. bieneusi has been detected in chickens, i.e. in a non
      mammalian species.

PMID- 12062550
TI  - Recent advances in Blastocystis hominis research: hot spots in terra incognita.
AB  - Despite being discovered more than 80 years ago, progress in Blastocystis
      research has been gradual and challenging, due to the small number of
      laboratories currently working on this protozoan parasite. To date, the
      morphology of Blastocystis hominis has been extensively studied by light and
      electron microscopy but all other aspects of its biology remain little explored
      areas. However, the availability of numerous and varied molecular tools and their
      application to the study of Blastocystis has brought us closer to understanding
      its biology. The purpose of this review is to describe and discuss recent
      advances in B. hominis research, with particular focus on new, and sometimes
      controversial, information that has shed light on its genetic heterogeneity,
      taxonomic links, mode of transmission, in vitro culture and pathogenesis. We also
      discuss recent observations that B. hominis has the capacity to undergo
      programmed cell death; a phenomenon similarly reported for many other unicellular
      organisms. There are still many gaps in our knowledge of this parasite. Although
      there is a growing body of evidence suggesting that B. hominis can be pathogenic
      under specific conditions, there are also other studies that indicated otherwise.
      Indeed, more studies are warranted before this controversial issue can be
      resolved. There is an urgent need for the identification and/or development of an
      animal model so that questions on its pathogenesis can be better answered.
      Another area that requires attention is the development of methods for the
      transfection of foreign/altered genes into B. hominis in order to facilitate
      genetic experiments.

PMID- 12062552
TI  - Host manipulation by Ligula intestinalis: a cause or consequence of parasite
      aggregation?
AB  - Previous investigations suggest that the infection of the cyprinid roach, Rutilus
      rutilus, with the larval plerocercoid forms of the cestode, Ligula intestinalis,
      creates behavioural and morphological changes in the fish host, potentially of
      adaptive significance to the parasite in promoting transmission to definitive
      avian hosts. Here we consider whether these behavioural changes are important in
      shaping the distribution of parasite individuals across the fish population. An
      examination of field data illustrates that fish infected with a single parasite
      were more scarce than expected under the negative binomial distribution, and in
      many months were more scarce than burdens of two, three or more, leading to a
      bimodal distribution of worm counts (peaks at 0 and >1). This scarcity of single
      larval worm infections could be accounted for a priori by a predominance of
      multiple infection. However, experimental infections of roach gave no evidence
      for the establishment of multiple worms, even when the host was challenged with
      multiple intermediate crustacean hosts, each multiply infected. A second
      hypothesis assumes that host manipulation following an initial single infection
      leads to an increased probability of subsequent infection (thus creating a
      contagious distribution). If manipulated fish are more likely to encounter
      infected first-intermediate hosts (through microhabitat change, increased
      ingestion, or both), then host manipulation could act as a powerful cause of
      aggregation. A number of scenarios based on contagious distribution models of
      aggregation are explored, contrasted with alternative compound Poisson models,
      and compared with the empirical data on L. intestinalis aggregation in their
      roach intermediate hosts. Our results indicate that parasite-induced host
      manipulation in this system can function simultaneously as both a consequence and
      a cause of parasite aggregation. This mutual interaction between host
      manipulation and parasite aggregation points to a set of ecological interactions
      that are easily missed in most experimental studies of either phenomenon.

PMID- 12062551
TI  - Biochemical characterisation of the 56 and 82 kDa immunodominant gametocyte
      antigens from Eimeria maxima.
AB  - Two immunodominant gametocyte antigens from Eimeria maxima with M(r) 56 kDa and
      M(r) 82 kDa have been identified previously as potential candidates for inclusion
      in a recombinant subunit vaccine against coccidiosis in poultry. Here, these
      proteins have been biochemically characterised, immunolocalised within the
      parasite, and sequences for their amino termini determined. These antigens co
      purify by affinity chromatography suggesting an interaction with each other.
      However, separation of the proteins by sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) in the absence of beta-mercaptoethanol did not reveal
      the presence of inter-chain disulphide bonds. The true masses of the 56 and 82
      kDa antigens are 52450 and 62450 Da, respectively, as determined by mass
      spectrometry. TX-114 separations suggested that they exist, in part, as soluble
      proteins within the parasite, and immunolocalisation studies indicated that they
      were found in the wall forming bodies of macrogametocytes. Separation of the
      proteins by 2D SDS-PAGE revealed that they are acidic in nature and heterogeneous
      in charge. Cleavage by neuraminidase and O-glycosidase indicated that the
      presence of O-linked glycans contributed to some of the charge microheterogeneity
      of both proteins. The absence of these O-glycans however, did not abolish
      antibody recognition, suggesting that the development of a recombinant subunit
      vaccine is possible. A more extensive investigation of the carbohydrate moieties
      of these proteins revealed that they also possess glucose, fucose, mannose and
      galactose. There was no evidence for the presence of N-linked glycans. The 56 and
      82 kDa antigens were separated from a mixture of proteins in a crude gametocyte
      lysate by 2D SDS-PAGE, the proteins isolated, and the N-terminus amino acid
      sequence determined. They showed no homology to each other at the N-terminus, or
      to any other previously characterised protein. Characterisation of these novel
      proteins has provided further insights into the molecular mechanisms of
      gametocyte differentiation in E. maxima.

PMID- 12062553
TI  - Incomplete feminisation by the microsporidian sex ratio distorter, Nosema
      granulosis, and reduced transmission and feminisation efficiency at low
      temperatures.
AB  - We investigated the effects of temperature on transovarial transmission and
      feminisation by Nosema granulosis, a microsporidian sex ratio distorter of the
      brackish water amphipod Gammarus duebeni. There was no difference in parasite
      transmission efficiency to the F(1) eggs of infected females maintained under two
      temperature conditions, 5 and 10 degrees C (89 and 86%, respectively). When F(1)
      individuals were screened as adults, the proportion infected was also similar at
      both temperatures (74 and 75%, respectively). However, transmission to the eggs
      of the F(2) generation was significantly reduced at low temperatures (61% at 5
      degrees C and 91% at 10 degrees C). In addition, feminisation efficiency was
      reduced substantially at low temperatures; at 10 degrees C, a calculated 85% of
      infected males were feminised, but at 5 degrees C only 49% were feminised. This
      is the first evidence for incomplete feminisation and temperature-dependent
      transmission and feminisation by this sex ratio distorter. We examine the
      consequences for parasite spread and maintenance in natural populations using a
      model to predict parasite prevalence in large populations. Reduced feminisation
      at low temperatures impedes the spread of the parasite so that it attains a
      substantially lower frequency, or may even be excluded, from host populations.

PMID- 12062554
TI  - A cement protein of the tick Rhipicephalus appendiculatus, located in the
      secretory e cell granules of the type III salivary gland acini, induces strong
      antibody responses in cattle.
AB  - Protein components of the cement cone of ixodid ticks are candidates for
      inclusion in vaccines against tick infestation, since they are essential for tick
      attachment and feeding. We describe here the cloning of a cDNA encoding a 36 kDa
      protein, designated Rhipicephalus Immuno-dominant Molecule 36 (RIM36), present in
      salivary glands and the cement cone material secreted by Rhipicephalus
      appendiculatus. The 334-amino-acid sequence of RIM36 has a high content of
      glycine, serine and proline. The protein contains a predicted N-terminal signal
      peptide and two classes of glycine-rich amino acid repeats, a GL[G/Y/S/F/L]
      tripeptide and a GSPLSGF septapeptide. Comparison of genomic and cDNA sequences
      reveals a 597 bp intron within the 3' end of the RIM36 gene. Immuno-electron
      microscopy demonstrates that RIM36 is predominantly located in the e cell
      granules of the type III salivary gland acini. An Escherichia coli recombinant
      form of the proline-rich C-terminal domain of RIM36 reacts with antisera from Bos
      indicus cattle, either experimentally infested with R. appendiculatus, or exposed
      to ticks in the field. The 36 kDa protein is strongly recognised on Western blots
      of salivary gland lysates and soluble extracts of purified R. appendiculatus
      cement cones by polyclonal antibodies generated against recombinant RIM36, and by
      antisera from cattle experimentally infested with ticks. The data indicate that
      this tick cement component is a target of strong antibody responses in cattle
      exposed to feeding ticks.

PMID- 12062556
TI  - Rapid genotyping of loci involved in antifolate drug resistance in Plasmodium
      falciparum by primer extension.
AB  - Current methods used to genotype point mutations in Plasmodium falciparum genes
      involved in resistance to antifolate drugs include restriction digestion of PCR
      products, allele-specific amplification or sequencing. Here we demonstrate that
      known point mutations in dihydrofolate reductase and dihydropteroate synthase can
      be scored quickly and accurately by single-nucleotide primer extension and
      detection of florescent products on a capillary sequencer. We use this method to
      genotype parasites in natural infections from the Thai-Myanmar border. This
      approach could greatly simplify large-scale screening of resistance mutations of
      the type required for evaluating and updating antimalarial drug treatment
      policies. The method can be easily adapted to other P. falciparum genes and will
      greatly simplify scoring of point mutations in this and other parasitic
      organisms.

PMID- 12062555
TI  - Populational structure of Schistosoma mansoni assessed by DNA microsatellites.
AB  - DNA microsatellites were used as molecular markers to analyse the population
      structure of the laboratory LE strain and of 10 field isolates of Schistosoma
      mansoni, the aetiologic agent of schistosomiasis. Out of 16,000 DNA sequences
      analysed in databases, 622 microsatellite loci were identified in 481 sequences
      (3.0%). The AT repetitions were the most frequent, followed by AAT and AC. Six
      loci showing perfect repetitions were selected and used in the polymerase chain
      reaction to evaluate polymorphisms in the number of repeats. Two groups of worms
      were studied. The first group consisted of 78 individuals, 39 of each sex, of the
      LE strain. The second group of worms consisted of 10 field isolates: seven from
      humans and three from snails. Four of the six loci were polymorphic, containing
      11-17 alleles per locus. No linkage disequilibrium was observed among loci and
      none of the loci was sex linked. In both groups of worms, a significant deviation
      from Hardy-Weinberg equilibrium was observed. The observed heterozygosity was
      always lower than the expected one. The polymerase chain reaction primers were S.
      mansoni specific. The LE strain showed a lower total number of alleles or a lower
      average number of alleles/polymorphic locus than the field isolates, suggesting
      that 41 years of laboratory maintenance exerted selective pressure on the LE
      strain. The S. mansoni populations from the field were most genetically
      undifferentiated (R(ST)<0.027), suggesting a high gene flow among them. Our
      results showed the usefulness of microsatellites for population analysis of S.
      mansoni, offering a new alternative for a better understanding of schistosomiasis
      epidemiology.

PMID- 12062557
TI  - Direct visualisation of RNA editing within a Leishmania tarentolae mitochondrial
      extract.
AB  - The coding sequence within several mitochondrial mRNAs of the trypanosomatid
      protozoa is created through editing by the precise insertion and deletion of U
      nucleotides. The biochemical characterisation of the editing reaction in the
      Leishmania genus of the trypanosomatids has been hindered by the lack of a direct
      in vitro assay. We describe here the first direct assay for the detection of
      guide RNA-directed editing mediated by a mitochondrial extract prepared from two
      independent isolates of Leishmania tarentolae. The assay enabled the editing
      activity within a L. tarentolae mitochondrial extract to be significantly
      enriched and will facilitate the characterisation of the editing reaction. The
      results suggest that the difficulty in establishing an assay for the L.
      tarentolae reaction was not simply a result of the catalytic machinery being
      limiting but rather reflected the presence of constraints on both the guide RNA
      and mRNA sequences.

PMID- 12062558
TI  - Immunisation of mice against neosporosis.
AB  - In the present study a murine encephalitis model was used to investigate if
      protection against neosporosis could be achieved by immunisation. Groups of 10
      mice were immunised with a sublethal dose of live Neospora caninum tachyzoites,
      N. caninum antigens incorporated into iscoms, N. caninum lysate mixed with Quil
      A, or N. caninum lysate in PBS. Control mice were given Quil A only. Challenge
      infection with 2.5x10(6) N. caninum tachyzoites resulted in clinical symptoms
      that remained until the end of the experiment in the controls. In contrast, mice
      immunised with live parasites or parasite lysate in Quil A only showed mild and
      transient symptoms. Of nine mice immunised with N. caninum iscoms, seven
      recovered while two died. Most severely affected were the mice immunised with
      parasite lysate only; all of them died within 28 days post-infection.
      Histological examination and scoring of brain lesions gave a significantly lower
      (P<0.0001) lesion score in mice immunised with live parasites than in controls.
      The groups immunised with iscoms or lysate and Quil A also had reduced lesion
      scores (P<0.04 and 0.07, respectively) but not the group given parasite lysate
      alone. The lesions seen in the latter group differed from those in the other
      groups. There was less cellular reaction and more tachyzoites indicating an
      active infection. The N. caninum specific antibody responses and cytokine
      production (IFN-gamma, IL-4 and IL-5) of splenocytes were analysed at the time of
      challenge infection. The results suggest a correlation between protection and
      high levels of IFN-gamma. Also, the immune responses recorded in mice immunised
      with parasite lysate without adjuvant were relatively weak and more towards the
      Th2 type, when compared with the other immunisation schedules. This is consistent
      with the weaker inflammatory response observed in the brains of these mice.

PMID- 12062559
TI  - Characterisation of a novel transporter from Cryptosporidium parvum.
AB  - P-ATPases are transmembrane proteins that hydrolyse ATP to drive cations or other
      substances across biomembranes. In this study we present the characterisation of
      a novel P-ATPase from the apicomplexan parasite Cryptosporidium parvum
      (CpATPase3), an opportunistic pathogen in autoimmune deficiency syndrome
      patients, for which no treatment is available. The single copy gene encodes 1488
      amino acids, predicting a protein of 169.7 kDa. Primary sequence analysis, as
      well as an extensive phylogenetic reconstruction, indicated CpATPase3 belongs to
      a novel class of eukaryotic-specific P-ATPases (Type V) with undefined substrate
      preferences. Transcription and translation of the gene were confirmed by reverse
      transcriptase polymerase chain reaction, and Western blot analysis of sporozoite
      protein extracts. Immunofluorescent microscopy of C. parvum sporozoites using
      rabbit antiserum raised against a glutathione-S-transferase-CpATPase3 (GST-ATP3)
      fusion protein showed that the parasite transporter was located within the apical
      complex associated with the parasite host-invasion machinery. Overall, these data
      demonstrate the diversity of C. parvum transporters, and raise the potential of
      Type V P-ATPases as apicomplexan-specific drug targets.

PMID- 12062560
TI  - Trypanosoma cruzi reinfections in mice determine the severity of cardiac damage.
AB  - In two murine models we studied Trypanosoma cruzi reinfection in the acute and
      chronic phase of experimental Chagas' disease in order to elucidate the relevance
      of reinfections in determining the variability of cardiac symptoms and the
      irreversible cardiac damage. They were followed for 120 and 600 days post
      infection (p.i.) for the acute and chronic model, respectively. Reinfected mice
      reached higher parasitaemia levels than infected mice. The survival was 33 and
      21% in the chronic phase for mice reinfected in the acute phase and 13% for mice
      reinfected in the chronic stage at the end of the experiments. Sixty-six percent
      of the infected group presented electrocardiographic abnormalities (heart
      frequency, prolonged PQ segment or QRS complex) in the chronic stage whereas 100%
      of the reinfected animals exhibited electric cardiac dysfunction since 90 and 390
      days p.i. for the acute and chronic reinfected model, respectively (P<0.01).
      Heart histopathological studies showed fibrosis and necrosis areas and
      mononuclear infiltrates supporting the view that parasite persistence is a major
      factor in continuing the tissue inflammation. This work shows that T. cruzi
      reinfections could be related to the variability and severity of the clinical
      course of Chagas' disease and that parasite persistence is involved in
      exacerbation of the disease.

PMID- 12062563
TI  - Diversity of benzimidazole-resistance alleles in populations of small ruminant
      parasites.
AB  - The resistance of gastro-intestinal nematodes of small ruminants (sheep and goat)
      to benzimidazole anthelmintic drugs seems to be linked primarily to a single
      mutation in the isotype 1 beta-tubulin gene. This study was carried out to
      investigate the origin and diversity of benzimidazole-resistance alleles in
      trichostrongylid nematodes. We sequenced a 550 bp fragment of the isotype 1 beta
      tubulin gene from several benzimidazole-resistant Teladorsagia circumcincta
      populations isolated from dairy goat farms in the central and south-western
      France. We also sequenced the same beta-tubulin fragment from Trichostrongylus
      colubriformis and Haemonchus contortus populations in south-western France. We
      found eight benzimidazole-resistance alleles in all T. circumcincta populations
      studied, six in H. contortus populations, and only one in T. colubriformis
      populations. In most cases, only one benzimidazole-resistance allele was present
      in T. circumcincta and H. contortus populations, but two alleles were found in a
      fewer number of them. Some T. circumcincta populations shared the same
      benzimidazole-resistance allele whereas some others had a specific benzimidazole
      resistance allele. Similar findings were obtained for H. contortus. As no
      parasites are introduced once the flock of dairy goat farms has been constituted,
      these data indicate for the three studied species that rare pre-existing
      benzimidazole-resistance alleles already present before the isolation of
      populations had been selected. On the other hand, the fact that some
      benzimidazole-resistance alleles were specific to one population of T.
      circumcincta or H. contortus, seems to be in agreement with the hypothesis of the
      selection of spontaneous mutations. Thus, the origin of benzimidazole-resistance
      alleles in trichostrongylid nematodes seems to involve primarily the selection of
      rare alleles and possibly of spontaneous mutations.

PMID- 12062562
TI  - Identification of a host-associated species complex using molecular and
      morphometric analyses, with the description of Gyrodactylus rugiensoides n. sp.
      (Gyrodactylidae, Monogenea).
AB  - Gyrodactylus rugiensis was originally described as a parasite occurring on the
      marine gobies Pomatoschistus minutus and Pomatoschistus microps. In our
      preliminary survey this species was also frequently found on Pomatoschistus
      pictus and Pomatoschistus lozanoi. Subsequent molecular analysis of the internal
      transcribed spacers rDNA region revealed that this parasite actually represents a
      complex of two apparently cryptic species, one restricted to P. microps and the
      other shared by P. minutus, P. lozanoi and P. pictus. Morphometric analyses were
      conducted on 17 features of the opisthaptoral hard parts of specimens collected
      from all four host species. Standard discriminant analysis showed a clear
      separation of both genotypes by significant differences in marginal hook and
      ventral bar features. Statistical classifiers (linear discriminant analysis and
      nearest neighbours) resulted in an estimated misclassification rate of 4.7 and
      3.1%, respectively. Based on molecular, morphological and statistical analyses a
      new species, Gyrodactylus rugiensoides is described. This species seems to
      display a lower host-specificity than generally observed for Gyrodactylus species
      as it infects three sympatric host species.However, seasonal and host-dependent
      morphometric variation is shown for G. rugiensoides collected on P. pictus. Host
      switching and gene flow might be important factors preventing speciation on
      closely related and sympatric host species. The presence of host associated
      species complexes in this Gyrodactylus-Pomatoschistus system is also confirmed by
      the presence of two host-dependent genotypes within G. micropsi found on P.
      minutus and P. lozanoi, and P. microps, respectively. By comparing host and
      parasite phylogeny, phylogenetic and ecological factors influencing host
      specificity are discussed.

PMID- 12062561
TI  - Significance of inducible nitric oxide synthase in acute myocarditis caused by
      Trypanosoma cruzi (Tulahuen strain).
AB  - Chagas' disease, caused by Trypanosoma cruzi, is associated with myocarditis and
      expression of myocardial cytokines and inducible nitric oxide synthase (NOS2). To
      assess the functional significance of NOS2 in murine Chagas' disease, we infected
      NOS2 knockout (NOS2(-/-)) and C57BL/6x129sv (wild type) mice with the Tulahuen
      strain of T. cruzi. Serial transthoracic echocardiography was performed to assess
      the progression of left and right ventricular dysfunction in infected mice.
      Uninfected wild type and NOS2(-/-) mice served as controls. At day 10 post
      infection (p.i.), infected wild type mice had larger left ventricular end
      diastolic diameter (2.52+/-0.14-vs-2.11+/-0.06 mm, P<0.02) and right ventricle
      (0.6+/-0.2-vs-0 visual grade, P<0.02) as compared with uninfected wild type mice.
      At day 19 p.i., compared with uninfected controls, infected wild type mice had
      larger left ventricular end-diastolic diameter (3.30+/-0.29-vs-2.11+/-0.07 mm),
      left ventricular end-systolic diameter (1.86+/-0.29-vs-0.88+/-0.05 mm), right
      ventricle (1.6+/-0.2-vs-0 visual grade), lower heart rate (413+/-27-vs-557+/-25
      beats per min), left ventricular relative wall thickness (0.44+/-0.05-vs-0.64+/
      0.03) and fractional shortening (45+/-4-vs-57+/-2%) [P<0.05 for all]. In
      contrast, no differences in left ventricular end-diastolic diameter or fractional
      shortening were noted among infected and uninfected NOS2(-/-) mice at day 19 p.i.
      Compared with uninfected controls, infected NOS2(-/-) mice had significantly
      lower heart rate (272+/-23-vs-512+/-31 beats per min, P<0.01) and larger right
      ventricle (0.6+/-0.2-vs-0, P<0.05 visual grade). The magnitude of right
      ventricular dilation in NOS2(-/-) mice was less than that observed in infected
      wild type mice. At necropsy, the heart weight was greater (129+/-16-vs-109+/-7
      mg, P=0.02) and myocardial inflammation more severe in infected wild type
      compared with infected NOS2(-/-) mice. Myocardial interleukin (IL)-1beta, IL-6,
      tumour necrosis factor-alpha, and interferon-gamma were induced in all infected
      mice. These data indicate that nitric oxide derived from NOS2 plays an important
      role in the development and progression of ventricular dilation and systolic
      dysfunction in acute murine chagasic myocarditis caused by infection with the
      Tulahuen strain.

PMID- 12062564
TI  - Chronic imipramine enhances 5-HT(1A) and 5-HT(2) receptors-mediated inhibition of
      panic-like behavior in the rat dorsal periaqueductal gray.
AB  - Electrical stimulation of the dorsal periaqueductal gray (DPAG) has been used to
      induce panic-like behavior in rats. In the present study, we investigated the
      effect of chronic imipramine treatment on the sensitivity of different 5-HT
      receptor subtypes in inhibiting aversion induced by electrical stimulation of
      this brain area. For that, the effects of intra-DPAG administration of the
      endogenous agonist 5-HT (20 nmol), the 5-HT(1A) receptor agonist 8-OH-DPAT (8
      nmol) and the 5-HT(2A/2C) receptor agonist DOI (16 nmol) were measured in female
      Wistar rats given either chronic injection of imipramine (15 mg/kg, 3 weeks, ip)
      or saline. The results showed that the three receptor agonists raised the
      threshold of aversive electrical stimulation in both groups of animals, but this
      antiaversive effect was significantly higher in rats treated with imipramine.
      Treatment with imipramine did not change the basal threshold of aversive
      electrical stimulation measured before intra-DPAG injection of the 5-HT agonists.
      The results suggest that sensitization of both 5-HT(1A) and 5-HT(2) receptors
      within the DPAG may be involved in the beneficial effect of imipramine in panic
      disorder (PD).

PMID- 12062565
TI  - Attenuation of the amphetamine discriminative cue in rats with the atypical
      antipsychotic olanzapine.
AB  - Sixteen male Sprague-Dawley rats were trained to discriminate between saline and
      amphetamine injections (1.0 mg/kg ip) using a standard two-lever (FR10) drug
      discrimination paradigm. A baseline dose-effect curve was generated for
      amphetamine administration alone, using doses both above and below the training
      dose (0.0-2.2 mg/kg ip). Once completed, a single dose of olanzapine (OLZ; 1.5
      mg/kg sc) was tested for its ability to attenuate the amphetamine cue. OLZ
      pretreatment (60 min) successfully interfered with an animal's ability to
      discriminate amphetamine injections across various doses. The percentage of
      correct responding on the amphetamine lever and rate of responding were both
      significantly decreased across some but not all of the amphetamine doses.
      Therefore, we believe that this preliminary investigation has successfully shown
      that an OLZ dose of 1.5 mg/kg sc at 60 min can interfere with an animal's ability
      to detect some subjective cue(s) associated with amphetamine administration.

PMID- 12062566
TI  - Amino acid and monoamine alterations in the cerebral cortex and hippocampus of
      mice submitted to ricinine-induced seizures.
AB  - The alkaloid ricinine isolated from the plant Ricinus communis, when administered
      to mice at high doses, induces clonic seizures accompanied by
      electroencephalographic alterations in the cerebral cortex and hippocampus. The
      lethal nature of ricinine-induced seizures is considered to be a good model for
      the study of the events that cause death during clonic seizures, particularly
      those related to respiratory spasms. The initial signs (pre-seizure period) were
      marked by exophthalmus and decreased locomotor behavior. Animals killed during
      the preseizure period presented an increased utilization rate (HVA/DA) of
      dopamine (DA), an increased concentration of noradrenaline (NA), and a decreased
      concentration of glutamate (Glu), glutamine (Gln), taurine (Tau), and serotonin
      (5-HT) in the cerebral cortex. The seizure period is characterized by the
      occurrence of hind limb myoclonus and respiratory spasms, which are followed by
      death. Alterations in the cerebral cortex concentration of these
      neurotransmitters persisted during the seizure period. These alterations are only
      partially observed in the hippocampus, mainly during the seizure period. The
      present results suggest that an increased release of Glu in the cerebral cortex
      can be implicated in the genesis of the ricinine-induced seizure and that it
      triggers many anticonvulsive mechanisms, like the release of Tau, DA, 5-HT, and
      NA.

PMID- 12062567
TI  - Intravenous ethanol/cocaine self-administration initiates high intake of
      intravenous ethanol alone.
AB  - Evidence suggests that ethanol (EtOH) preexposure influences the rewarding
      valence of subsequent EtOH use. This study was conducted to determine if EtOH
      preexposure through EtOH/cocaine self-administration facilitates the motivational
      effects of EtOH alone. Rats self-administered intravenous (iv) EtOH/cocaine
      combinations (EtOH/Cocaine Fading group; EtOH 125.0 mg/kg/inj+Cocaine 0.1-0.75
      mg/kg/inj) during a preexposure period. Consequently, these rats self
      administered intravenous EtOH alone (62.5, 125.0, 250.0 and 500.0 mg/kg/inj)
      significantly more than a control group with prior cocaine self-administration
      experience (0.1-0.75 mg/kg/inj). In addition, at equal EtOH intake levels,
      locomotor activity was significantly enhanced in the EtOH/Cocaine Fading group
      but not the Cocaine Control animals (P=.01). The amount of EtOH self-administered
      in the EtOH/Cocaine Fading group during 1-h sessions (approximately 0.5-2.0 g/kg)
      corresponded with blood alcohol levels (BAL) ranging from 44 to 221 mg/dl. The
      highest BALs reported here have not previously been demonstrated after voluntary
      EtOH intake through any route of administration. These data suggest that
      preexposure to EtOH during EtOH/cocaine self-administration sessions modified
      neural substrates underlying both the reinforcing and locomotor responses to EtOH
      alone. Further studies utilizing intravenous EtOH self-administration will allow
      identification of various long-term behavioral and neural consequences of
      voluntary high EtOH intake.

PMID- 12062568
TI  - Effects of prenatal cocaine exposure on latent inhibition in 1-year-old female
      rats.
AB  - Prenatal cocaine exposure has been shown to produce attentional changes in human
      infants and children, as well as in preweanling and young adult animals. The aim
      of the current study was to determine whether attentional effects of in utero
      cocaine exposure persist into middle adulthood. Sprague-Dawley dams received
      twice-daily subcutaneous (sc) administration of either 20 mg/kg cocaine HCl or
      0.9% saline vehicle from Gestational Day 8 to 20. Saline-injected dams were pair
      fed to cocaine-injected subjects during prenatal treatment. A second control
      group received no treatment and had ad lib access to food. One-year-old female
      offspring were tested for latent inhibition (LI) of a context conditioning task,
      using freezing and vertical nose crossing (VNC) as behavioral measures of fear.
      Although freezing did not reveal any differences between prenatal treatment
      groups, a cocaine-dependent reduction in baseline VNC indicated that cocaine
      exposed adult offspring were less explorative than controls. In addition, cocaine
      exposed animals showed enhanced LI as measured by greater levels of VNC than
      controls in the context preexposed condition of the task. These results provide
      insight into the nature of attentional contributions to prenatal cocaine effects
      on learning and indicate that such effects persist well into adulthood.

PMID- 12062569
TI  - Comparison of the reinforcing efficacy of two dopamine D2-like receptor agonists
      in rhesus monkeys using a progressive-ratio schedule of reinforcement.
AB  - High-efficacy D2-like dopamine (DA) receptor agonists can function as positive
      reinforcers when made available to animals for intravenous self-administration
      under a fixed-ratio (FR) schedule of reinforcement. In a previous study, however,
      low-efficacy D2-like agonists failed to maintain self-administration under an FR
      schedule, suggesting that agonist efficacy is directly related to efficacy as a
      positive reinforcer. To examine this hypothesis further, the present study
      compared two D2-like DA receptor agonists that maintained FR responding, but
      differ in their D2-like receptor efficacy and selectivity, using a procedure
      designed to rank-order drugs according to their efficacy as reinforcers. Rhesus
      monkeys (n=5) were prepared with chronic, indwelling intravenous catheters and
      allowed to self-administer cocaine (0.1 mg/kg/injection) or saline on different
      days under a progressive-ratio (PR) schedule. When responding was stable, doses
      of the full D2-like agonist R(-)-propylnorapomorphine (NPA) or the partial D2
      like agonist R(-)-apomorphine (APO) were made available for self-administration
      in the test sessions. Both compounds maintained self-administration with
      sigmoidal or biphasic dose-response functions. Surprisingly, the lower efficacy
      agonist APO was the more efficacious positive reinforcer. This result fails to
      support the hypothesis that D2-like receptor efficacy is directly related to
      efficacy as a reinforcer. It is possible that other pharmacological effects,
      e.g., D1 receptor activity, influenced self-administration.

PMID- 12062570
TI  - Cannabis, tobacco, and caffeine use modify the blood pressure reactivity
      protection of ascorbic acid.
AB  - Cannabis, caffeine, and tobacco use are associated with increased mesolimbic
      dopamine activity. Ascorbic acid (AA) modulates some dopaminergic agent effects,
      and was recently found to decrease systolic blood pressure (SBP) stress
      reactivity. To examine how AA SBP stress reactivity protection varies by use of
      these substances, data from an AA trial (Cetebe, 3000 mg/day for 14 days; N=108)
      were compared by substance use level regarding SBP reactivity to the anticipation
      and actual experience phases of a standardized psychological stressor (10 min of
      public speaking and arithmetic). Self-reported never users of cannabis, persons
      not currently smoking tobacco, and persons consuming three or more caffeine
      beverages daily all exhibited AA SBP stress reactivity protection to the actual
      stressor, but not during the anticipation phase. Conversely, self-reported ever
      cannabis users, current tobacco smokers, and persons consuming less than three
      caffeine beverages daily exhibited the AA SBP protection during the anticipation
      phase, but only the lower caffeine consumption group exhibited AA protection
      during both phases. Covariates (neuroticism, extraversion, and depression scores,
      age, sex, body mass index) were all nonsignificant. Results are discussed in
      terms of dopaminergic effects of these substances, modulation of
      catecholaminergic and endothelial activity, and AA support of coping styles.

PMID- 12062571
TI  - Role of the lateral septal noradrenergic system in the elaboration of male sexual
      behavior in rats.
AB  - The study was aimed at investigating the possible involvement of noradrenergic
      mechanisms in the lateral septum (LS) for elaboration of male sexual behavior in
      rats. In this study, norepinephrine (NE), yohimbine (YOH), isoproterenol (ISOP),
      propranolol (PROP), saline (SAL) and dimethyl sulfoxide (DMSO) were injected
      bilaterally in the LS in six different groups of sexually active male rats, and
      various components of sex behavior were recorded. The application of NE (3
      microg) and alpha(2)-antagonist YOH (1 microg) produced a stimulation of most of
      the components of male sexual behavior, and there was increase in sexual arousal
      as well as performance. The microinfusion of nonspecific beta-agonist ISOP (2
      microg) also produced a stimulation of copulatory behavior whereas beta
      antagonist PROP (2 microg) produced an inhibition. The stimulation of male sexual
      behavior by YOH application at the LS could be due to an increased release of NE
      by its blocking effect on presynaptic alpha(2)-receptors. These results suggest
      that the noradrenergic system in the LS has stimulatory effect upon male sexual
      behavior, probably acting through beta-receptors.

PMID- 12062572
TI  - Cocaine's effects on the discrimination of simple and complex auditory stimuli by
      baboons.
AB  - The effects of cocaine on tone frequency discriminations by baboons were examined
      and compared with previous data for more complex acoustic stimuli (speech sounds)
      to see if cocaine's perceptual effects on these discriminations depends upon the
      type of stimulus employed (i.e., tones vs. speech sounds). Baboons pressed a
      lever to produce one repeating "standard" tone and released the lever only when
      one of four other "comparison" tones occasionally occurred in place of the
      standard tone. Cocaine's effects were assessed once or twice weekly by giving an
      intramuscular injection of cocaine hydrochloride (0.01-0.56 mg/kg) immediately
      prior to performing the task and by examining correct detections and reaction
      times for each tone following drug administration. Cocaine impaired tone
      discriminability, with greater impairments occurring for those tones that were
      more similar in frequency to the standard tone. Cocaine's perceptual effects
      occurred within 20-70 min following drug administration. Cocaine also impaired or
      facilitated the speed of responding to auditory stimuli, depending upon the drug
      dose and subject. The results demonstrate that cocaine can impair auditory
      discriminations involving simple tones, as well as speech sounds, and further
      supports the suggestion that cocaine's effects are focused on CNS mechanisms
      related to the use of pitch cues.

PMID- 12062573
TI  - The dose-response effects of repeated subacute sarin exposure on guinea pigs.
AB  - The present study assessed the effects of repeated subacute exposure to the
      organophosphorous nerve agent, sarin. Guinea pigs were injected five times per
      week (Monday-Friday) for 2 weeks with fractions of the established LD(50) dose of
      sarin (42 microg/kg sc). The animals were assessed for the development of
      cortical EEG seizures. Changes in body weight, red blood cell (RBC)
      acetylcholinesterase (AChE) levels and neurobehavioral reactions to a functional
      observational battery were monitored over the 2 weeks of sarin exposure and for
      an extended postinjection period. There were dose-related changes in body weight
      and RBC AChE levels. No guinea pigs receiving 0.3, 0.4 or 0.5 x LD(50) of sarin
      showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as
      low as 10% of baseline. Seizures were evident in animals receiving 0.6 x LD(50)
      of sarin as early as the second day, and subsequent injections led to
      incapacitation and death. Animals receiving 0.5 x LD(50) sarin showed obvious
      signs of cholinergic toxicity, which included a significant increase in their
      angle of gait. Overall, 2/13 animals receiving 0.5 x LD(50) sarin died before all
      10 injections were given. By the 10th day of injections, the animals receiving
      saline were significantly easier to remove from their cages and handle as
      compared to the first day of injections. They were also significantly less
      responsive to an approaching pencil and touch on the rump in comparison to the
      first day of testing. In contrast, the animals receiving 0.4 x LD(50) sarin
      failed to show any significant reductions in their responses to an approaching
      pencil and a touch on the rump as compared to the first day. The 0.5 x LD(50)
      sarin animals failed to show any significant changes to the approach response and
      touch response and did not adjust to handling or cage removal from the first day
      of injections to the last day of handling. In summary, the guinea pigs receiving
      the 0.4 x LD(50) and 0.5 x LD(50) doses of sarin failed to habituate to some
      aspects of the functional observational battery testing.

PMID- 12062574
TI  - Effect of electroacupuncture on response to immobilization stress.
AB  - Forced immobilization is a simple and effective stressor which produces large
      increases in heart rate (HR), blood pressure (BP), and plasma levels of
      norepinephrine (NE) and epinephrine (EPI). This study investigated the effects of
      electroacupuncture on BP, HR, and plasma catecholamine levels in rats challenged
      with immobilization stress. Male Sprague-Dawley rats received electroacupuncture
      (3 Hz, 0.2 ms pulses, 20 mA) for 30 min after start of immobilization stress (180
      min). Needlepoints corresponded to Shaohai (HT3) and Neiguan (PC6) on the heart
      and pericardium channel. BP and HR were monitored with an indwelling carotid
      catheter, and blood samples were taken from the jugular vein. Blood (for HPLC
      determination of NE and EPI), mean BP, and HR were sampled at rest and during the
      immobilization stress at 15, 30, 60, 90, 120, 150, and 180 min.
      Electroacupuncture at HT3 and PC6 points but not at control points (TE5, LI11,
      and tail) significantly reduced the expected increases in BP, HR, and attenuated
      plasma levels of NE and EPI in response to 3 h of immobilization stress. Results
      provide strong evidence that electroacupuncture effectively reduces BP and HR
      increases and plasma catecholamine increases in rats challenged with
      immobilization stress.

PMID- 12062575
TI  - Effects of dopamine agonists and antagonists on locomotor activity in male and
      female rats.
AB  - Male and female Sprague-Dawley rats were treated with cocaine, the specific
      dopamine uptake inhibitor GBR 12909, the dopamine D1 agonist SKF 82958 or the
      dopamine D2 agonist quinpirole. After treatment, the rats were placed in an
      activity chamber for 30 min and locomotor activity was monitored. Cocaine, GBR
      12909 and SKF 82958 all increased locomotor activity in both males and females,
      but greater increases were observed in females. In contrast, quinpirole produced
      decreases in activity, with males showing greater decreases than females.
      Separate groups of animals were given SCH 23390 or eticlopride prior to cocaine.
      The D1 antagonist SCH 23390 reduced the locomotor activating effects of cocaine
      in both males and females, with females showing greater sensitivity to SCH 23390.
      The D2 antagonist eticlopride also reduced the locomotor activating effects of
      cocaine, with no clear differences between males and females. These results
      suggest that the differences between males and females in their locomotor
      response to cocaine can be at least partially attributed to differences in the
      function of dopamine D1 and D2 receptors.

PMID- 12062576
TI  - Nicotine-alcohol interactions and cognitive function in rats.
AB  - Nicotine and ethanol are the most widely abused drugs in the world. They are very
      often used and abused together. However, little is known about the functional
      interaction of nicotine and ethanol. The current project studied the interactive
      effects of nicotine and ethanol on working memory in the eight-arm radial maze.
      Adult female rats were trained on a radial arm maze for 18 sessions to reach
      asymptotic levels of choice accuracy. During the maintenance phase of radial arm
      maze testing, which indexed working memory function, the rats were injected with
      nicotine (0, 0.15, 0.3, 0.6, and 1.2 mg/kg sc, 20 min before testing) with and
      without ethanol pretreatment (0 or 1.5 g/kg, 16% v/v ip, 30 min before testing).
      All animals received the treatments in a counterbalanced order with at least 1
      week between treatments. Higher doses of nicotine had a significant interaction
      with ethanol in terms of radial arm maze choice accuracy. Nicotine plus ethanol
      coadministration precipitated a significant choice accuracy impairment at doses
      that when given alone had no effect on performance. At the lower dose range of
      nicotine, ethanol coadministration eliminated the nicotine-induced memory
      improvement. No significant effects were seen with either nicotine or ethanol
      treatment or their interaction on response latency in the radial arm maze. The
      nicotine-ethanol interactive effects on memory were compared with the interaction
      of their well-characterized hypothermic effects. Nicotine and alcohol, when
      injected separately or in combination, induced hypothermia with no significant
      interactive effect. This study found that ethanol blocked low-dose nicotine
      induced memory improvement and precipitated memory impairment with high-dose
      nicotine treatment. This interaction may be an important consideration for
      nicotine and ethanol coabuse and the possible therapeutic use of nicotinic drugs
      for memory dysfunction.

PMID- 12062577
TI  - Effects of agmatine on the escalation of intravenous cocaine and fentanyl self
      administration in rats.
AB  - Escalation of drug intake reliably occurs when animals are allowed extended self
      administration access. As a form of plasticity, escalation of drug intake may be
      accompanied by neuroadaptive changes that are related to the transition from
      controlled use to addiction. The purpose of the present experiment was to examine
      the effects of agmatine (decarboxylated L-arginine) on the escalation of
      intravenous (iv) fentanyl and cocaine self-administration in rats. Subjects were
      allowed 12 h of daily access to fentanyl (2.5 microg/kg) or cocaine (0.2 mg/kg)
      under a fixed-ratio (FR) 1 schedule of reinforcement for 30 days. Animals self
      administering fentanyl were distributed into three groups: (1) low-dose agmatine
      (10 mg/kg) throughout self-administration; (2) high-dose agmatine (30 mg/kg)
      throughout self-administration; and (3) high-dose agmatine after significant
      escalation (Day 18) of drug intake had occurred. Animals in a fourth group were
      pretreated with a high dose of agmatine throughout 30 days of cocaine self
      administration. Both doses of agmatine, when given throughout self
      administration, significantly decreased the escalation of responding that
      occurred for fentanyl but not cocaine. In the group that received agmatine after
      significant escalation had occurred, fentanyl-maintained responding was not
      significantly altered. These data indicate that agmatine attenuates the
      escalation of fentanyl self-administration if administered before the escalation
      begins and may mediate neuroadaptive events related to chronic opioid self
      administration.

PMID- 12062578
TI  - Uranyl acetate-induced sensorimotor deficit and increased nitric oxide generation
      in the central nervous system in rats.
AB  - We investigated the effects of uranyl acetate on sensorimotor behavior,
      generation of nitric oxide and the central cholinergic system of rats. Male
      Sprague-Dawley rats were treated with intramuscular injection of 0.1 and 1 mg/kg
      uranyl acetate in water, daily for 7 days. Control animals received equivalent
      amount of water. The treatment was stopped after the seventh injection because
      the animals in the 1-mg/kg group appeared lethargic. The animals were maintained
      for an additional observation period of 30 days. The study was initiated as a
      dose-finding study that covered doses of 10 and 100 mg/kg, as well. However, all
      the animals in the 100-mg/kg treatment group died after the third and fourth
      injections, and all animals given 10 mg/kg died after the fifth and sixth
      injections. On Day 30 following the cessation of treatment, the sensorimotor
      functions of the animals in the 0.1- and 1-mg/kg treatment groups were evaluated
      using a battery of tests that included measurements of postural reflexes, limb
      placing, orientation to vibrissae touch, grip time, beam walking and inclined
      plane performance. The animals were sacrificed the same day and the cerebral
      cortex, brainstem, cerebellum and midbrain were dissected. The levels of nitric
      oxide as marker for increased oxidative stress, and the integrity of the
      cholinergic system as reflected in acetylcholinesterase (AChE) activity and m2
      muscarinic acetylcholine receptors ligand binding, were determined. The data from
      behavioral observations show that there was a dose-related deficit at the 0.1-
      and 1-mg/kg treatment groups for inclined plane performance. Both doses reduced
      grip time, but there was no significant difference between the two doses.
      Similarly, both beam-walk score and beam-walk time were impaired at both doses as
      compared with the controls. A significant increase in nitric oxide was seen at
      0.1 mg/kg dose in cortex and midbrain, whereas brainstem and cerebellum showed an
      insignificant decrease at both the doses. Similarly, there was no significant
      change in nitric oxide levels in kidneys and liver of the treated animals as
      compared with the controls. There was a significant increase in AChE activity in
      the cortex of the animals treated with 1 mg/kg uranyl acetate, but not in other
      brain regions. Ligand binding densities for the m2 muscarinic receptor did not
      show any change. These results show that low-dose, multiple exposure to uranyl
      acetate caused prolonged neurobehavioral deficits after the initial exposure has
      ceased.

PMID- 12062579
TI  - Central administration of mCPP, a serotonin 5-HT(2B/2C) agonist, decreases water
      intake in rats.
AB  - In the present study, we investigated in rats the effect of third ventricle
      injections of 1-(3-chlorophenyl)piperazine (mCPP), a 5-HT(2) receptor agonist, on
      water intake induced by three different physiological stimuli: fluid deprivation,
      acute salt load and hypovolemia. Injections of mCPP in the doses of 80 and 160
      nmol/rat were able to decrease water intake in all three conditions studied.
      Third ventricle injections of mCPP (160 nmol/rat) were no longer able to diminish
      water intake in the groups of rats pretreated with central injections of an
      equimolar amount of (+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo[1,7
      bc][2,6]-naphthyridine (SDZ SER 082), a selective 5-HT(2B/2C) antagonist. The
      central administration of mCPP (160 nmol/rat) was not able to modify the intake
      of a 0.1% saccharin solution. It is suggested that the central activation of a 5
      HT(2B/2C) component is able to impair the drive for water intake induced by the
      physiological stimuli represented by fluid deprivation, acute salt load and
      hypovolemia. This effect seems not to be consequent on a general nonspecific
      central nervous system depression or on a locomotor deficit, because saccharin
      intake is not affected by third ventricle injections of mCPP.

PMID- 12062580
TI  - Combined 192 IgG-saporin and 5,7-dihydroxytryptamine lesions in the male rat
      brain: a neurochemical and behavioral study.
AB  - In a previous experiment [Eur J Neurosci 12 (2000) 79], combined
      intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT; 150
      microg) and 192 IgG-saporin (2 microg) in female rats produced working memory
      impairments, which neither single lesion induced. In the present experiment, we
      report on an identical approach in male rats. Behavioral variables were locomotor
      activity, T-maze alternation, beam-walking, Morris water-maze (working and
      reference memory) and radial-maze performances. 192 IgG-saporin reduced
      cholinergic markers in the frontoparietal cortex and the hippocampus. 5,7-DHT
      lesions reduced serotonergic markers in the cortex, hippocampus and striatum.
      Cholinergic lesions induced motor deficits, hyperactivity and reduced T-maze
      alternation, but had no other effect. Serotonergic lesions only produced
      hyperactivity and reduced T-maze alternation. Beside the deficits due to
      cholinergic lesions, rats with combined lesions also showed impaired radial-maze
      performances. We confirm that 192 IgG-saporin and 5,7-DHT injections can be
      combined to produce concomitant damage to cholinergic and serotonergic neurons in
      the brain. In female rats, this technique enabled to show that interactions
      between serotonergic and basal forebrain cholinergic mechanisms play an important
      role in cognitive functions. The results of the present experiment in male rats
      are not as clear-cut, although they are not in obvious contradiction with our
      previous results in females.

PMID- 12062581
TI  - Ginkgo biloba extract: cognitive enhancer or antistress buffer.
AB  - Constituents extracted from the leaves of the Ginkgo biloba tree possess
      beneficial properties that may buffer the aging nervous system from deterioration
      due to oxidative stress. In the present investigation, a standardized extract of
      G. biloba (EGb 761) or an equal volume of the vehicle was administered (100
      mg/kg/day) to senescent (20-month) C57BL/6 male mice for up to 82 consecutive
      days. Animals were tested twice in the Morris water maze (MWM) after 28 and 70
      days of treatment. No differences were observed in acquisition or retention of
      performance on the water maze. Elevated-plus maze (EPM) trials were conducted
      prior to and subsequent to the chronic treatment regimen. Marked baseline
      differences in plus-maze performance were present in the first experiment. A
      second experiment used a matched-pairs design to minimize preexisting
      differences. Results supported the hypothesis that EGb 761 may serve as an
      antistress buffer, attenuating the increase in anxiety typically observed in
      animals after cold water exposure. Tissue samples from the hippocampus and cortex
      were analyzed by Western blot for the transcription factor cyclic-AMP response
      element binding (CREB) protein. EGb 761 had no significant effect on
      immunoreactivity to CREB from either the hippocampus or the cerebral cortex.

PMID- 12062582
TI  - Reinforcing effects of the neurosteroid allopregnanolone in rats.
AB  - The GABA(A) receptor positive modulator allopregnanolone (3alpha-hydroxy-5alpha
      pregnan-20-one) is a potent neurosteroid with behavioral and biochemical
      characteristics similar to ethanol, barbiturates, and benzodiazepines. This
      suggests that neurosteroids may provide an alternative class of
      sedative/hypnotic, anticonvulsant, and anxiolytic pharmacotherapies. However,
      there is evidence from animal models that neurosteroids may be susceptible to
      abuse by humans. Thus, the present study evaluated the reinforcing effects of
      orally administered allopregnanolone in rats. In the first experiment, male Long
      Evans rats (n=9) were allowed to voluntarily consume a 50-microg/ml
      allopregnanolone (50A) solution or water in an unlimited-access two-bottle choice
      procedure for 10 days. Subsequently, the same animals were trained to lever-press
      to receive a 50A solution in daily 30-min operant sessions using a sucrose
      substitution procedure. In the two-bottle choice procedure, rats consumed
      significantly more allopregnanolone than water, suggesting that allopregnanolone
      was serving as a reinforcer. In the operant self-administration procedure,
      allopregnanolone did not maintain levels of responding that were different from
      water, suggesting that allopregnanolone did not function as a reinforcer in this
      procedure. These results suggest that orally administered allopregnanolone
      possesses reinforcing properties; however, additional studies are necessary to
      determine whether operant oral self-administration will be a viable index of
      allopregnanolone's reinforcing effects.

PMID- 12062583
TI  - Evidence for opponent-process actions of intravenous cocaine and cocaethylene.
AB  - The affective response to cocaine (COC) has been suggested to follow a time
      course and pattern that adheres to the prediction of opponent-process models of
      drug actions. While the initial impact of the drug is positive, within a few
      minutes that effect wanes and is replaced by an aversive state characterized by
      anxiety and drug craving. We have demonstrated this phenomenon in animals by
      showing that rats prefer distinctive environments associated with the immediate
      effects of intravenous COC (1.0 mg/kg) but avoid environments associated with the
      state present 15-min postinjection. Human addicts have reported taking ethanol
      with their COC as a means of attenuating the negative aftereffects of COC
      administration. The combination of ethanol and COC results in the production of
      cocaethylene (CE), a metabolite of COC having psychostimulant properties. The
      current study was devised to assess whether the immediate and delayed affective
      responses to CE might account for the self-medication strategy of COC addicts
      pretreating themselves with ethanol. Rats developed conditioned place preferences
      for environments paired with the immediate effects of a 1.44-mg/kg intravenous
      dose of CE (equimolar to a 1.0-mg/kg dose of COC). While no aversive effects were
      observed at 0, 5, or 15 min postinjection, reliable place avoidance was detected
      for an environment paired with the internal state present 30-min post-CE. These
      data are consistent with the view that the development of CE may account for
      efficacy of ethanol to delay and weaken the aversive aftereffects of COC.

PMID- 12062584
TI  - Inhibitory action of halothane on rat masculine sexual behavior and sperm
      motility.
AB  - Adult male rats were exposed to inhale halothane in the following regime: 15
      ppm/4 h/5 days/week/9 weeks. Sexual behavior observations and sperm motility test
      were made before halothane exposure (0 days) and at 15, 30, 45 and 60 days of
      exposure. Fifteen days after halothane exposure, this anesthetic inhibited the
      proportion of animals displaying ejaculation. In those animals ejaculating,
      halothane produced an inhibition of masculine sexual behavior reflected as an
      increase in the intromission latency, number of mounts and postejaculatory
      interval. At 30 days after exposure, only an increase in the intromission latency
      was observed. At 45 and 60 days, the inhibitory effect of halothane on sexual
      behavior disappeared. Similarly, at 15 and 30 days, but not at 45 or 60 days of
      halothane exposure, a reduced sperm motility was observed. Such transient effects
      of halothane suggest the development of tolerance to the inhibitory actions of
      this anesthetic on sexual behavior and sperm motility. These halothane effects
      are in line with an inhibition of masculine sexual behavior after stimulation of
      the GABAergic system.

PMID- 12062586
TI  - Modulation of mood and cognitive performance following acute administration of
      Melissa officinalis (lemon balm).
AB  - Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys
      contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It
      has been suggested, in light of in vitro cholinergic binding properties, that
      Melissa extracts may effectively ameliorate the cognitive deficits associated
      with Alzheimer's disease. To date, no study has investigated the effects on
      cognition and mood of administration of Melissa to healthy humans. The present
      randomised, placebo-controlled, double-blind, balanced-crossover study
      investigated the acute effects on cognition and mood of a standardised extract of
      M. officinalis. Twenty healthy, young participants received single doses of 300,
      600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day
      intervals. Cognitive performance was assessed using the Cognitive Drug Research
      (CDR) computerised test battery and two serial subtraction tasks immediately
      prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50)
      concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine
      from nicotinic and muscarinic receptors in human occipital cortex tissue were
      also calculated. Results, utilising the cognitive factors previously derived from
      the CDR battery, included a sustained improvement in Accuracy of Attention
      following 600 mg of Melissa and time- and dose-specific reductions in both
      Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed
      by Bond-Lader mood scales, was elevated at the earliest time points by the lowest
      dose, whilst "alertness" was significantly reduced at all time points following
      the highest dose. Both nicotinic and muscarinic binding were found to be low in
      comparison to the levels found in previous studies.

PMID- 12062585
TI  - Experimental conditions for the continuous subcutaneous infusion of four central
      analgesics in rats.
AB  - For the analysis of pharmacotherapeutic regimens for chronic pain in animals, it
      is important to establish delivery methods in which analgesics can be
      administered continuously and at a constant rate for a prolonged period of time.
      This allows for the assessment of how drug effects may vary over time in the
      presence of ongoing pain. The present study determined, for four analgesic
      compounds, the maximal doses that met all of the following criteria: (i) water
      soluble, (ii) stable over 14 days at 38 degrees C, and (iii) devoid of
      undesirable side-effects in normal rats, as assessed by evolution of body weight
      and temperature after the subcutaneous implantation of an osmotic mini-pump that
      continuously infused the compounds over a 14-day period. The results showed the
      maximal doses to be 5 mg/rat/day for morphine hydrochloride, 2.5 mg/rat/day for
      imipramine hydrochloride, 20 mg/rat/day for ketamine hydrochloride, and 10
      mg/rat/day for gabapentin. These doses were further found to be sufficient to
      express each compound's representative pharmacological activity. The conditions
      identified here appear appropriate for future studies of these four compounds in
      rat models of chronic pain and neuropathic allodynia.

PMID- 12062587
TI  - Anticonvulsive activity of Butea monosperma flowers in laboratory animals.
AB  - The bioassay-guided fractionation of dried flowers of Butea monosperma (BM) was
      carried out to isolate the active principle responsible for its anticonvulsant
      activity. The petroleum ether extract was fractionated by column chromatography
      using solvents of varying polarity such as n-hexane, n-hexane:ethyl acetate,
      ethyl acetate, and methanol. The anticonvulsive principle of B. monosperma was
      found to be a triterpene (TBM) present in the n-hexane:ethyl acetate (1:1)
      fraction of the petroleum ether extract. TBM exhibited anticonvulsant activity
      against seizures induced by maximum electroshock (MES) and its PD(50) was found
      to be 34.2+/-18.1 mg/kg. TBM also inhibited seizures induced by pentylenetetrazol
      (PTZ), electrical kindling, and the combination of lithium sulfate and
      pilocarpine nitrate (Li-Pilo). However, TBM was not effective against seizures
      induced by strychnine and picrotoxin. TBM exhibited depressant effect on the
      central nervous system. After repeated use for 7 days, the PD(50) (MES) of TBM
      increased to 51.5+/-12.1 mg/kg. Similarly, after repeated use of TBM, the
      duration of sleep induced by pentobarbital was not reduced significantly. Further
      studies are required to investigate its usefulness in the treatment of epilepsy.

PMID- 12062588
TI  - One-trial tolerance to midazolam is due to enhancement of fear and reduction of
      anxiolytic-sensitive behaviors in the elevated plus-maze retest in the rat.
AB  - The anxiolytic-like effects of benzodiazepines (BZDs) in rats is reduced after a
      single exposure to the elevated plus-maze test (EPM). Several hypotheses have
      been formulated but no conclusive explanation exists for this phenomenon called
      "one-trial tolerance." In this study, we examined this phenomenon further by
      carrying out an ethopharmacological analysis of the behavior of rats submitted to
      the EPM in two trials. Rats injected with saline before both trials (control),
      treated with 1.0 mg/kg of midazolam before both trials (MM), or only before Trial
      2 (SM), were exposed to the EPM. The SM group did not differ from the controls in
      the Trial 1 and Trial 2 conditions. The MM group showed a clear anxioselective
      profile in Trial 1 and no anxiolytic-like effects in Trial 2. Whereas midazolam
      injected before the first trial caused no significant change in immobility, there
      was a pronounced increase in immobility during Trial 2 for all three conditions.
      These data suggest that the anxiolytic-like action of midazolam in the first
      trial gives way to the fear-related insensitive behaviors (phobic/avoidance
      responses) responsible for the one-trial tolerance to BZDs in Trial 2.
      Furthermore, an additional experiment showed that midazolam does not seem to
      affect the acquisition of the learned avoidance response since it is present upon
      retesting even after midazolam administration in Trial 1 (MS group). Rather, the
      present data suggest an emotional shift from Trial 1 to Trial 2, which leads to
      change in the responsiveness of the animals to BZDs.

PMID- 12062589
TI  - Dorsal and median raphe serotonergic system lesion does not alter the opiate
      withdrawal syndrome.
AB  - Previous pharmacological studies have implicated serotonergic brain systems in
      opiate withdrawal. To test the hypothesis that serotonin (5-HT) has a critical
      role in the development of opiate withdrawal, we have employed a near-total brain
      5-HT system lesion technique (90% depletion) using 5,7-dihydroxytryptamine
      combined with induction of opiate dependence by implantation of morphine pellets
      or by repeated injections of increasing doses of morphine. The effects of
      serotonergic neuron lesion were examined on spontaneous opiate withdrawal
      (changes in circadian locomotor activity) and naloxone-precipitated opiate
      withdrawal syndrome (the somatic aspect). The antiwithdrawal properties of
      clonidine, an alpha(2)-adrenoceptor agonist currently used for clinical treatment
      for the somatic signs of opiate withdrawal, were tested also in the lesioned
      rats. Our findings show that serotonergic lesions in morphine-dependent rats did
      not alter either the spontaneous or the naloxone-induced withdrawal syndrome
      (with exception of jumping behavior). Moreover, clonidine alleviated the naloxone
      induced withdrawal syndrome in lesioned as well as in sham-operated morphine
      dependent rats. These results demonstrate that 5-HT systems are not directly
      responsible for the development of the somatic opiate withdrawal syndrome in
      morphine-dependent rats.

PMID- 12062590
TI  - Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by
      allopregnanolone and midazolam.
AB  - The effects of allopregnanolone and midazolam, given intracerebroventricularly,
      on the behavioral and biochemical effects of picrotoxin, were examined in a model
      of neurotoxin-induced seizures, in mice. After acute injections, midazolam
      (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.0 nmol) produced similar and
      dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given
      intraperitoneally at the ED(85) dose decreased significantly the concentration of
      serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4
      dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex,
      in the period of time immediately preceding the onset of seizures. A single
      injection of allopregnanolone more potently, in comparison to midazolam,
      antagonized the biochemical action of picrotoxin, abolishing its effects on DA,
      HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These
      results for the first time provide a direct argument for an involvement of
      central dopaminergic and serotonergic systems in the seizure development. The
      present data add also to the accumulating evidence suggesting a favorable
      pharmacological profile for some neurosteroids currently considered to have a
      future role in the management of epilepsy.

PMID- 12062591
TI  - Effects of corticotropin-releasing hormone on distress vocalizations and
      locomotion in maternally separated mouse pups.
AB  - The behavioral effects of corticotropin-releasing hormone (CRH) appear to depend
      on the baseline state of arousal of the animal. In this study, this hypothesis
      was tested using a 4-min maternal separation procedure in 7-day-old male and
      female mouse pups (outbred CFW strain). Two intensities of stress were used to
      assess the effects of intracerebroventricularly administered r/hCRH: a mild
      stress condition where the ambient temperature was close to nest temperature (30
      degrees C) and rates of maternal separation-induced ultrasonic vocalizations
      (USVs) were relatively low (ca. 25/4 min), and a more stressful condition where
      the temperature was 19 degrees C and the rates of USVs were high (ca. 250/4 min).
      Differential effects of CRH on vocalization rate and locomotor behavior were
      observed to be dependent on the level of stress. In the more stressful 19 degrees
      C condition, r/hCRH dose-dependently reduced the number of USVs without affecting
      motor behavior, as indexed by grid crossings. In contrast, in the 30 degrees C
      condition, only the highest dose of r/hCRH reduced calling while r/hCRH activated
      motor behavior over a wider range of doses. These effects were independent of
      hypothalamus-pituitary-adrenal (HPA) axis activity, as measured by plasma
      corticosterone levels. The present study indicates that in mouse pups, the
      effects of CRH administration depend on baseline levels of arousal and that the
      behavioral effects of CRH administration can be dissociated under mild and more
      stressful conditions.

PMID- 12062592
TI  - A multi-institutional review of radiosurgery alone vs. radiosurgery with whole
      brain radiotherapy as the initial management of brain metastases.
AB  - PURPOSE: Data collected from 10 institutions were reviewed to compare survival
      probabilities of patients with newly diagnosed brain metastases managed initially
      with radiosurgery (RS) alone vs. RS + whole brain radiotherapy (WBRT). METHODS
      AND MATERIALS: A database was created from raw data submitted from 10
      institutions on patients treated with RS for brain metastases. The major
      exclusion criteria were resection of a brain metastasis and interval from the end
      of WBRT until RS >1 month (to try to ensure that the up-front intent was to
      combine RS + WBRT and that RS was not given for recurrent brain metastases).
      Survival was estimated using the Kaplan-Meier method from the date of first
      treatment for brain metastases until death or last follow-up. Survival times were
      compared for patients managed initially with RS alone vs. RS + WBRT using the Cox
      proportional hazards model to adjust for known prognostic factors or Radiation
      Therapy Oncology Group recursive partitioning analysis (RPA) class. RESULTS: Out
      of 983 patients, 31 were excluded because treatment began after 6/1/98; 159 were
      excluded because brain metastases were resected; 179 were excluded because there
      was an interval >1 month from WBRT until RS; and 45 were excluded for other
      reasons. Of the 569 evaluable patients, 268 had RS alone initially (24% of whom
      ultimately had salvage WBRT), and 301 had RS + up-front WBRT. The median survival
      times for patients treated with RS alone initially vs. RS + WBRT were 14.0 vs.
      15.2 months for RPA Class 1 patients, 8.2 vs. 7.0 months for Class 2, and 5.3 vs.
      5.5 months for Class 3, respectively. With adjustment by RPA class, there was no
      survival difference comparing RS alone initially to RS + up-front WBRT (p = 0.33,
      hazard ratio = 1.09). CONCLUSIONS: Omission of up-front WBRT does not seem to
      compromise length of survival in patients treated with RS for newly diagnosed
      brain metastases.

PMID- 12062593
TI  - Analysis of repeat stereotactic radiosurgery for progressive primary and
      metastatic CNS tumors.
AB  - PURPOSE: To identify and evaluate the pretreatment and patient factors that would
      predict for complications after repeat radiosurgery. METHODS AND MATERIALS: The
      data from 26 patients who underwent re-irradiation with Gamma Knife surgery after
      a previous procedure in the same or subjacent location were available for
      evaluation. The range of follow-up was 1-45 months (mean 10). The mean minimal
      and maximal initial dose and volume for all 26 patients was 16.2 Gy (range 12
      22), 31.0 Gy (range 22.2-40.0), and 12.4 cm(3) (range 1.20-70.84), respectively.
      The mean marginal and maximal repeated radiosurgery dose and volume for all 26
      patients was 14.9 Gy (range 12-22.5), 29.7 Gy (range 18.0-45.0) and 12.8 cm(3)
      (range 1.10-39.20), respectively. RESULTS: Tumor control was significantly better
      statistically (p = 0.0129) for benign tumors (6 of 6, 100% actuarial rate at 4
      years) compared with malignant tumors (7 of 20, 35% actuarial rate at 3 years, 3
      of 4 metastatic tumors and 2 of 10 primary malignant gliomas). The retreatment
      volume for radiosurgery correlated significantly with the probability of
      neurologic decline (any cause) (p = 0.0181). CONCLUSION: Repeat radiosurgery can
      be performed for recurrent tumors with minimal central nervous system toxicity,
      especially for benign tumors, with reasonable tumor control.

PMID- 12062594
TI  - Craniopharyngioma: the St. Jude Children's Research Hospital experience 1984
      2001.
AB  - PURPOSE: To review our institution's experience in the treatment of
      craniopharyngioma and assess the merits of initial therapy with limited surgery
      and irradiation. METHODS AND MATERIALS: The data of 30 patients (median age 8.6
      years) with a diagnosis of craniopharyngioma between April 1984 and September
      1997 were reviewed. Their course of treatment, neurologic, endocrine, and
      cognitive function, and quality of life at last follow-up were compared. RESULTS:
      Fifteen patients were initially treated with surgery (8 required irradiation
      after relapse) and 15 with limited surgery and irradiation (2 required additional
      treatment for tumor progression). Only 1 patient died of tumor progression. The
      surgery group lost a mean of 9.8 points in full-scale IQ, and the combined
      modality group lost only 1.25 points (p <0.063). Patients in the surgery group
      who had relapses (n = 9) lost a mean of 13.1 points (p <0.067). A loss of 10
      points was considered clinically significant. The surgery group also had more
      frequent neurologic, ophthalmic, and endocrine complications. The mean Health
      Utility Index (a functional quality-of-life index) was higher for the combined
      modality group (0.85) than for the surgery group (0.71; p <0.063, one-sided t
      test). CONCLUSIONS: The acute neurologic, cognitive, and endocrine effects of
      surgery often affect long-term function and quality of life. Our experience
      suggests that limited surgery and radiotherapy cause lesser or comparable
      sequelae. Diabetes insipidus was the only endocrine deficiency that differed
      substantially in frequency between the two groups. Newer radiation planning and
      delivery techniques may make a combined-modality approach a good initial option
      for most patients.

PMID- 12062595
TI  - Hypothyroidism in children with medulloblastoma: a comparison of 3600 and 2340
      cGy craniospinal radiotherapy.
AB  - PURPOSE: To determine if low-dose craniospinal irradiation (2340 cGy) with
      chemotherapy is associated with a lower incidence of hypothyroidism compared to
      standard dose (3600 cGy) with or without chemotherapy in children with
      medulloblastoma. PATIENTS AND METHODS: Between 1980 and 1999, 32 patients < or
      =20 years old survived after craniospinal irradiation with or without
      chemotherapy. Twenty patients received 3600 cGy craniospinal irradiation (CSI),
      whereas 12 had 2340 cGy CSI; all patients received a posterior fossa boost to a
      total dose 5040-5580 cGy. The median ages at the time of CSI for those receiving
      2340 cGy and 3600 cGy were 7.2 and 10.2 years, respectively. Chemotherapy (CT)
      was employed in 22 children. All children who received 2340 cGy had CT consisting
      of vincristine, CCNU, and either cisplatin or cyclophosphamide. Ten of 20 (50%)
      patients receiving 3600 cGy had CT; the most common regimen was vincristine,
      CCNU, and prednisone. Serum-free thyroxine and thyroid-stimulating hormone
      concentrations were measured in all children at variable times after
      radiotherapy. Thyroid-stimulating hormone responses to i.v. thyrotrophin
      releasing hormone were assessed in those suspected of having central
      hypothyroidism. Median follow-up for children receiving 2340 cGy was 5 years
      (range: 2-11.2 years), whereas for those receiving 3600 cGy, follow-up was 12.5
      years (range: 2.4-20 years). RESULTS: Eighteen patients (56%) developed
      hypothyroidism at a median time after radiotherapy of 41 months (range: 10 months
      to 18 years). Primary hypothyroidism was more common than central hypothyroidism
      (38% and 19%). All 7 children <5 years developed hypothyroidism, whereas 9 of 15
      (60%) ages 5-10 and 2 of 10 (20%) age >10 years had hypothyroidism (p < 0.001).
      Hypothyroidism was documented in 10 of 12 (83%) who had 2340 cGy + CT, 6 of 10
      (60%) who had 3600 cGy + CT, and 2 of 10 (20%) who had 3600 cGy without CT (p <
      0.025). CONCLUSIONS: Current treatment regimens consisting of chemotherapy and
      2340 cGy craniospinal irradiation followed by a posterior fossa boost for
      medulloblastoma do not show a reduction of hypothyroidism. Young age and use of
      chemotherapy were associated with a higher incidence of hypothyroidism.

PMID- 12062597
TI  - Twice daily irradiation increases locoregional control in patients with medically
      inoperable or surgically unresectable stage II-IIIB non-small-cell lung cancer.
AB  - PURPOSE: To evaluate the effect of q.d. or b.i.d. radiotherapy (RT) on the
      outcome of patients with locally advanced non-small-cell lung cancer. METHODS AND
      MATERIALS: We retrospectively reviewed the outcome of 261 patients with medically
      inoperable or surgically unresectable Stage II-IIIB non-small-cell lung cancer,
      who were treated with combined modality cisplatin-based chemotherapy and RT.
      Chemotherapy was administered either sequentially or concurrently with thoracic
      RT. The median follow-up was 18 months (range 2-92). Treatment groups included
      sequential chemotherapy and q.d. RT (n = 109), concurrent chemotherapy and q.d.
      RT (n = 48), and concurrent chemotherapy and b.i.d. RT (n = 104). Of the 261
      patients, 97% had a Karnofsky performance score > or =80, and 86.2% had < or =5%
      weight loss in the 3 months before diagnosis; 66.7% had nonsquamous cell
      histologic features. All but 8 patients had Stage IIIA-B disease. RESULTS: The 2-
      and 5-year locoregional control rate was 42.4% and 25.7% for the q.d. group and
      70.6% and 45.8% for the b.i.d. group, respectively (p = 0.0001). The 2- and 5
      year disease-free survival rate was 26.7% and 6.5% for the q.d. group and 39.6%
      and 27.3% for the b.i.d. group, respectively (p = 0.0114). The corresponding
      overall survival rates were 35.9% and 9.4% for the q.d. group and 38.7% and 26.1%
      for the b.i.d. group. No difference was found in the rate of distant metastasis
      between the 2 groups. Multivariate analysis indicated that b.i.d. RT was a
      favorable prognostic factor for locoregional control and disease-free survival.
      CONCLUSION: RT b.i.d. significantly improved locoregional control and disease
      free survival compared with RT q.d. in patients with Stage IIIA-B non-small-cell
      lung cancer.

PMID- 12062596
TI  - Randomized phase II chemotherapy and radiotherapy trial for patients with locally
      advanced inoperable non-small-cell lung cancer: long-term follow-up of RTOG 92
      04.
AB  - PURPOSE: The standard treatment for patients with locally advanced inoperable non
      small-cell lung cancer and good prognostic factors has become combined
      chemotherapy (ChT) and radiotherapy (RT). However, the sequencing of the two
      modalities, as well as fractionation of RT, has been controversial. The Radiation
      Therapy Oncology Group (RTOG) Study 92-04 was a randomized Phase II study
      designed to evaluate further the toxicity and efficacy of 2 different strategies
      of chemoradiation evaluated in 2 prior RTOG Phase II studies. METHODS: Patients
      with Stage II or III medically inoperable or unresectable non-small-cell lung
      cancer, good performance status, and minimal weight loss were enrolled into a
      prospective randomized Phase II RTOG study. Arm 1 consisted of induction ChT
      (vinblastine 5 mg/m(2) i.v. bolus weekly for the first 5 weeks, and cisplatin,
      100 mg/m(2) i.v. on Days 1 and 29) followed by concurrent ChT/RT (cisplatin 75
      mg/m(2) i.v. on Days 50, 71, and 92) during thoracic radiotherapy (63 Gy in 34
      fractions during 7 weeks starting on Day 50). Arm 2 was concurrent ChT and
      hyperfractionated RT starting on Day 1 with a total dose of 69.6 Gy in 58
      fractions during 6 weeks, 1.2 Gy/fraction b.i.d. ChT consisted of cisplatin, 50
      mg/m(2) i.v. on Days 1 and 8, and oral VP-16, 50 mg b.i.d. for 10 days only on
      the days of thoracic radiotherapy repeated on Day 29. RESULTS: A total of 168
      patients were entered between 1992 and 1994, and 163 patients were eligible for
      analysis. Eighty-one patients were treated in Arm 1 and 82 patients in Arm 2.
      Pretreatment characteristics, including age, gender, Karnofsky performance
      status, histologic features, and stage, were similar. The incidence of acute
      esophagitis was significantly higher among patients treated in Arm 2 than among
      those treated in Arm 1 (p <0.0001). The incidence of acute hematologic toxicity
      was significantly higher among patients treated in Arm 1 (p = 0.01 for anemia and
      p = 0.03 for other hematologic toxicities) than among those treated in Arm 2.
      Analysis of late toxicity showed that chronic esophageal toxicity was
      significantly more frequent in Arm 2 than in Arm 1 (p = 0.003). The time to in
      field progression was significantly different (p = 0.009), favoring Arm 2
      compared with Arm 1 (26% vs. 45% with failure in 2 years and 30% vs. 49% with
      failure in 4 years, respectively). The median 2-year and overall 5-year survival
      rates were similar between the two arms. CONCLUSION: Concurrent ChT and
      hyperfractionated RT resulted in a significant prolongation of the time to in
      field progression, but with higher acute and chronic esophagitis. No other
      significant differences were observed between the two groups. Investigation with
      a chemoradio-protector is under way.

PMID- 12062598
TI  - Measurement of lung tumor volumes using three-dimensional computer planning
      software.
AB  - PURPOSE: To examine the interclinician variation in the definition of gross tumor
      volume (GTV) in patients undergoing radiotherapy for non-small-cell lung cancer
      (NSCLC), develop methods to minimize this variation, and test these methods.
      METHODS AND MATERIALS: The radiotherapy planning computed tomography (CT) scans
      of 6 consecutive patients with NSCLC in which the radiologist was able to define
      and outline the GTV were used. Six oncologists independently contoured the tumors
      with the radiologist's markings as a guide using a three-dimensional treatment
      planning system. Separate contours were prepared using only mediastinal window
      settings and using both mediastinal and lung window settings. The volumes were
      calculated using the planning system software (series 1). Factors that resulted
      in interclinician variation were determined, and, after a 3-year interval, 5 of
      the 6 clinicians redefined the GTVs using a revised protocol aimed at minimizing
      variation (series 2). RESULTS: For series 1, the interclinician variation in the
      measurement of volumes ranged from 5%, in the most tightly measured tumor, to
      42%, in the most variable, but was, on average, 20%. Statistically significant
      differences were noted among the clinicians (p = 0.002), that is, some clinicians
      tended to record relatively small and some relatively large volumes. The reasons
      for the variation among the oncologists included a tendency to include regions
      with a low probability of containing tumor, as if the oncologist were contouring
      a target volume; inclusion of adjacent atelectasis (ignoring the radiologist's
      outline); and variable treatment of spicules. When the exercise was repeated
      using the revised protocol (series 2), the degree of interclinician variation was
      reduced, with a range of 7-22% (average 13%). In series 2, the differences among
      the clinicians were not statistically significant (p = 0.25). CONCLUSION: Despite
      major radiologic input, significant variation occurred in the delineation of the
      three-dimensional GTVs of NSCLC among oncologists. Standardization of the
      approach with guidelines resulted in a reduction in this variation.

PMID- 12062599
TI  - The role of p53 in radiation therapy outcomes for favorable-to-intermediate-risk
      prostate cancer.
AB  - PURPOSE: Some prostate cancers may have molecular alterations that render them
      less responsive to radiation therapy; identification of these alterations before
      treatment might allow improved treatment optimization. This study investigated
      whether p53, a potential molecular determinant, could predict long-term radiation
      therapy outcome in a restricted group of relatively favorable-risk prostate
      cancer patients treated uniformly with irradiation alone. METHODS AND MATERIALS:
      This study included 53 patients previously treated with radiotherapy for
      favorable-to-intermediate-risk prostate cancer. These patients were selected for
      relatively low pretreatment PSAs (< or =21 ng/mL) and Gleason scores (< or =7) to
      decrease the likelihood of nonlocalized disease, because disease localization was
      necessary to examine the efficacy of localized radiation therapy. The status of
      p53 was immunohistochemically assessed in paraffin-embedded pretreatment biopsy
      specimens, along with appropriate controls. This marker was selected based upon a
      usable mutation prevalence in early-stage prostate cancer and its potential
      linkage with radiation response via cell cycle, DNA repair, and cell death
      pathways. Correlation between p53 mutation and clinical outcome was analyzed in
      univariate and multivariate fashion and included conventional prognosticators,
      such as stage, grade, and PSA. Freedom from biochemical failure was determined
      using American Society for Therapeutic Radiology and Oncology criteria.
      Limitations of prior studies were potentially avoided by requiring adequate
      posttreatment follow-up (median follow-up in nonfailing patients of 5.1 years),
      as well as pretreatment PSA and Gleason scores that suggested localized disease,
      and uniformity of treatment. RESULTS: The total group of 53 favorable-to
      intermediate-risk patients demonstrated an actuarial biochemical failure rate of
      35% at 5 years. Forty percent of all specimens had a greater than 10% labeling
      index for p53 mutation, and actuarial biochemical control was found to strongly
      and independently correlate with p53 status. Patients with higher p53 labeling
      indices demonstrated significantly higher PSA failure rates (p < 0.001). In
      contrast, p53 status did not correlate with pretreatment PSA, grade, or tumor
      stage. Similarly, pretreatment PSA (log-rank 0.22), Gleason score (log-rank
      0.93), and T stage (log-rank 0.15) were not prognostic for outcome in this group
      of patients selected for their relatively favorable clinical characteristics.
      CONCLUSIONS: (1) p53 status in pretreatment biopsies strongly predicted for long
      term biochemical control after radiation therapy in favorable-to-intermediate
      risk prostate cancer patients. (2) If validated in other independent clinical
      data sets, p53 status should be considered as a stratification factor in future
      clinical trials and could be useful in guiding treatment. Abnormal p53 status
      might favor surgical management, aggressive dose escalation, or p53-targeted
      therapy.

PMID- 12062600
TI  - Clinical utility of the percentage of positive prostate biopsies in predicting
      prostate cancer-specific and overall survival after radiotherapy for patients
      with localized prostate cancer.
AB  - PURPOSE: To determine whether the percentage of positive prostate biopsies
      provides clinically relevant information to a previously established risk
      stratification system with respect to the end points of prostate cancer-specific
      survival (PCSS) and overall survival after radiotherapy for patients with
      clinically localized prostate cancer. METHODS AND MATERIALS: A Cox regression
      multivariable analysis was used to evaluate the ability of the percentage of
      positive prostate biopsies to predict PCSS and overall survival for 381 men who
      underwent radiotherapy for localized prostate cancer during the prostate-specific
      antigen era. RESULTS: At a median follow-up of 4.3 years (range 0.8-13.3), the
      presence of < or =50% positive biopsies vs. >50% positive biopsies provided a
      clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%,
      p = 0.004) in intermediate-risk patients. Moreover, all patients could be
      stratified into a minimal or high-risk cohort on the basis of the 10-year
      estimates of PCSS (100% vs. 55%, p <0.0001) and overall survival (87% vs. 40%, p
      = 0.02) by incorporating the percentage of positive prostate biopsy information
      into a previously established risk stratification system. CONCLUSION: The
      clinically relevant stratification of PCSS using the percentage of positive
      prostate biopsies in intermediate-risk patients confirms previous findings based
      on prostate-specific antigen outcome. These data provide evidence to support the
      ability to stratify newly diagnosed patients with clinically localized disease
      into a minimal-risk (low-risk + low biopsy volume [< or =50%] intermediate-risk)
      or high-risk (high biopsy volume [>50%] intermediate-risk + high-risk) cohort for
      prostate cancer-specific death after conventional dose radiotherapy. Additional
      follow-up and independent validation are needed to confirm these findings.

PMID- 12062601
TI  - Risk group stratification in patients undergoing permanent (125)I prostate
      brachytherapy as monotherapy.
AB  - PURPOSE: Patients undergoing prostate brachytherapy (PB) as monotherapy are often
      selected on the basis of favorable pretreatment factors. However, intermediate
      and high-risk prostate cancer patients are commonly offered PB as monotherapy
      without the addition of external beam radiotherapy (EBRT) or hormonal therapy.
      This series reports the outcome of patients undergoing PB as monotherapy who were
      stratified into low, intermediate, and high-risk groups with extended follow-up.
      METHODS AND MATERIALS: A total of 102 patients with clinically localized prostate
      cancer underwent PB alone as monotherapy. EBRT or hormonal therapy was not part
      of their initial treatment. Prostate-specific antigen (PSA) relapse-free survival
      (PRFS) was determined in accordance with the American Society for Therapeutic
      Radiology and Oncology consensus statement. Patients were stratified as at
      favorable risk (Stage T1-2a, pretreatment PSA < or =10.0 ng/mL, and Gleason score
      < or =6), intermediate risk (one prognostic indicator with a higher value), or
      unfavorable risk (> or =2 indicators with higher values). The median follow-up
      period for patients in this series was 7 years (range 2.1-9.7). The median age at
      treatment was 71 years (range 54-80), and the median prescribed dose of (125)I
      was 145 Gy. RESULTS: Forty patients experienced a biochemical relapse at a median
      of 1.9 years (range 0.4-4.2). The 5-year actuarial PRFS rate for patients with
      favorable, intermediate, and unfavorable risk was 85%, 63%, and 24%, respectively
      (p <0.0001). All but 1 patient had the relapse within the first 5 years of
      treatment. When stratifying patients on the basis of their pretreatment PSA
      level, the 5-year PRFS rate for men with a PSA < or =10 ng/mL vs. >10 ng/mL was
      78% vs. 35%, respectively (p = 0.0005). Furthermore, the 5-year PRFS rate for men
      with a Gleason score of < or =6 vs. > or =7 was 74% vs. 33%, respectively (p =
      0.0001). No difference was found between Stage T1-T2a and Stage T2b or higher
      (64% vs. 54%, respectively; p = 0.353). CONCLUSION: On the basis of risk
      stratification, PB as monotherapy produces comparable PRFS to EBRT and surgery at
      7 years of follow-up. PB as monotherapy is particularly ineffective in patients
      with unfavorable risk factors, and additional therapy is warranted.

PMID- 12062602
TI  - Analysis of intraprostatic failures in patients treated with hormonal therapy and
      radiotherapy: implications for conformal therapy planning.
AB  - PURPOSE: Conformal therapy of prostate cancer is based on high-dose irradiation
      to the entire prostate gland. The aim of this study was to analyze the pattern of
      intraprostatic recurrence in patients undergoing external beam radiotherapy
      (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses
      are adequate to control microscopic disease outside the primary tumor and
      therefore whether high-dose irradiation can be exclusively focused on the
      macroscopic disease. METHODS AND MATERIALS: The clinical and radiologic reports
      of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with
      hormonal therapy were evaluated. In all patients, before and after therapy, the
      size and site of the primary neoplasm within the prostate were assessed by
      clinical examination and imaging studies. RESULTS: With a median follow-up of 45
      months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve
      patients had an intraprostatic recurrence, with the appearance of a new nodule
      (in 5 patients with a complete response after therapy) or increased nodular size
      compared with the minimal size (in the 7 other patients). In all patients, on the
      basis of a semiquantitative evaluation of the site of recurrence, this was shown
      to originate within the initial tumor volume. CONCLUSION: The results of this
      analysis seem to confirm some histologic findings observed in patients undergoing
      prostatectomy for local recurrence after radiotherapy that suggest that local
      recurrence usually originates in the primary tumor rather than in focal prostatic
      intraepithelial neoplasia. This observation might justify the application of
      conformal therapy procedures aimed at identifying the gross tumor volume, in the
      phase of boost, exclusively with the primary tumor.

PMID- 12062603
TI  - Postoperative radiotherapy in 423 patients with pT3N0 prostate cancer.
AB  - PURPOSE: To evaluate the treatment outcome in pT3N0 patients with adenocarcinoma
      of the prostate treated with an elective course of postoperative irradiation
      (RT). METHODS AND MATERIALS: During a 22-year period, a total of 423 pT3N0
      prostate cancer patients were treated at a single medical center with prostatic
      fossa RT, which was the only adjuvant therapy given. The patient characteristics
      were as follows: median age 66 years; Stage pT3aN0 in 296 (70%) and pT3bN0 in 127
      (30%); Gleason score 2-4 in 12 (2.8%), 5-6 in 157 (37.1%), 7 in 151 (35.7%), and
      8-10 in 100 (23.6%); and the median and mean preoperative prostate-specific
      antigen (PSA) level was 10 and 15.9 ng/mL, respectively. Radiotherapy consisted
      of a median dose of 48 Gy delivered to the prostatic fossa and its immediate
      vicinity. The median follow-up was 7 years. RESULTS: The 5- and 10-year actuarial
      survival rate was 92% and 73%, respectively, and the 5- and 10-year disease-free
      survival rate (PSA <0.05 ng/mL) was 69% and 51%, respectively. In multivariate
      analysis, the Gleason score was the most important predictor for survival (p =
      0.00005), and pathologic stage and Gleason score were independently predictive of
      disease-free survival (p = 0.00007 and 0.0003, respectively). The worst
      prognostic category was represented by pT3bN0, Gleason score 7-10 patients who
      had a 5.3 times greater risk of tumor recurrence than those with pT3aN0, Gleason
      score 2-6. A high (>25 ng/mL) preoperative PSA level was also a predictor of
      tumor recurrence (p = 0.03). A total of 43 patients (10.2%) developed clinical
      recurrence. This included 30 patients (7%) with distant metastases alone and 13
      (3%) with local recurrence, which included 2 patients who also had distant
      disease. An additional 88 patients (20%) had PSA elevation (>0.05 ng/mL). This
      treatment program was well tolerated, with acute toxicity common (62%) but of no
      clinical significance. No late or severe toxicity was recorded. CONCLUSION:
      Adjuvant radiotherapy, as given in this study, appears to substantially reduce
      the expected incidence of local tumor recurrence in pT3N0 prostate cancer
      patients. The treatment outcome was poor in pT3bN0 and Gleason score 7-10
      patients, with >80% showing evidence of clinical or PSA recurrence at 10 years
      after therapy. This group should be the target of a prospective trial of systemic
      therapy.

PMID- 12062604
TI  - Impact of postimplant edema on V(100) and D(90) in prostate brachytherapy: can
      implant quality be predicted on day 0?
AB  - PURPOSE: To determine the effect of edema on the dosimetric parameters V(100)
      (percentage of prostate volume that received a dose equal to or greater than the
      prescribed dose) and D(90) (minimal dose delivered to 90% of prostate volume) in
      125I prostate brachytherapy and to determine whether the edema can be used to
      predict implant quality on the day of the implant (Day 0). METHODS AND MATERIALS:
      Fifty consecutive patients treated with (125)I implants who had two postimplant
      CT scans were selected for this study. The mean interval between the studies was
      46 +/- 23 days. The implants were preplanned to deliver 150 Gy to the prostate
      plus a 3-5-mm symmetric dose margin using peripherally loaded 0.4-0.6-mCi (NIST
      99) (125)I seeds. A dose-volume histogram was compiled for each postimplant CT
      scan. The V(100) and D(90) from the first and second CT scans were compared to
      determine the effect of edema on these parameters. A multivariate regression
      analysis was performed to define the linear relationships for predicting the
      V(100) or D(90) at 30-60 days after implant from the magnitude of the edema and
      the values of V(100) and D(90) on Day 0. RESULTS: V(100) and D(90) increased by
      5% +/- 6% and 15% +/- 17%, respectively, during the interval between the first
      and second postimplant CT scans. The mean edema was 1.53 +/- 0.20. The increases
      in V(100) and D(90) were found to be proportional to the edema and the values of
      V(100) and D(90) on Day 0. The increase in V(100) was also found to depend on the
      width of the preplan dose margin. Linear relationships were derived that predict
      the V(100) and D(90) at 30-60 days after implant with a standard error of +/-4%
      and +/-24 Gy, respectively. CONCLUSION: V(100) and D(90) increased by 5% +/- 6%
      and 15% +/- 17%, respectively, during the first 30-60 days after implant. The
      results of a multivariate linear regression analysis showed that the increases in
      V(100) and D(90) were proportional to both the magnitude of the edema and the
      values of these parameters on Day 0. The relationships derived by linear
      regression analysis predict V(100) and D(90) at 30-60 days after implant to
      within +/-4% and +/-24 Gy, respectively. However, predicting the 30-60-day V(100)
      and D(90) on Day 0 is a poor substitute for obtaining a 30-60-day CT scan,
      because the uncertainty in the predicted values is greater by a factor of > or
      =2. Nevertheless, on average, the predicted values should provide a more reliable
      estimate of the actual V(100) and D(90) than the Day 0 values that ignore the
      effect of edema altogether. The increase in V(100) was also found to depend on
      the width of the preplan dose margin; therefore, our results for V(100) are only
      valid for implants planned with a 3-5-mm margin.

PMID- 12062605
TI  - Saving bladders with brachytherapy: implantation technique and results.
AB  - PURPOSE: To analyze and report the treatment results of brachytherapy for
      solitary bladder cancer in the Arnhem Radiotherapy Institute. METHODS AND
      MATERIALS: Between January 1983 and October 1998, 63 patients with a solitary
      bladder tumor were treated with a combination of transurethral resection,
      external beam radiotherapy (EBRT), and interstitial radiotherapy. The indications
      for bladder-conserving treatment were tumor < or =5 cm, T1G3 (n = 14), T2G2 (n =
      8), T2G3 (n = 37), and T3a (n = 4). The prescribed implant dose was either 55 Gy
      (range 50-65 Gy) in combination with small pelvis external beam RT, 3-4 fractions
      of 3.5 Gy (n = 58), or 30 Gy in combination with 20 fractions of 2 Gy external
      beam radiotherapy (n = 5). Brachytherapy was performed with 2-8 137Cs needles
      until 1995 (n = 48) and 2-5 afterloading catheters (192Ir) since 1996 (n = 15).
      Follow-up cystoscopies were performed at 3-month intervals during the first 2
      years, then every 6 months for 3 years, and annually after the fifth year. The
      median follow-up was 4.9 years. RESULTS: Twenty patients developed local
      recurrences, of which 6 were "true in-implant recurrences," 12 were in second
      bladder locations, and 2 were urethral recurrences. All recurrences developed
      within 2.5 years after treatment. Of these 20 patients, 13 underwent cystectomy:
      6 stayed disease-free, 1 died of postoperative complications, 2 developed
      regional metastases, and 4 developed distant metastases. The 5-year disease
      specific survival rate was 80% for patients with Stage T1 and 60% for those with
      Stage T2 disease. The local control rate was 70% in the whole patient population
      and 80% after salvage cystectomy. Forty-four bladders were saved. Acute
      complications were seen in 14 patients, and no significant late complications
      occurred. CONCLUSION: Using this treatment technique, a high cure rate with
      conservation of the bladder and only minor toxicity can be obtained in a selected
      patient population having a solitary tumor < or =5 cm.

PMID- 12062606
TI  - Skin toxicity due to intensity-modulated radiotherapy for head-and-neck
      carcinoma.
AB  - PURPOSE: To investigate the cause of acute skin toxicity observed in the
      treatment of head-and-neck cancer with extended-field intensity-modulated
      radiotherapy (EF-IMRT). METHODS AND MATERIALS: EF-IMRT was used to treat head-and
      neck cancer, with the gross target volume receiving 70 Gy and the clinical target
      volume 60 Gy. A thermoplastic mask covering the head, neck, and shoulder was used
      for immobilization. Dosimetric studies were conducted to investigate the possible
      causes of the skin reactions, such as the bolus effect of the mask, the use of
      multiple tangential beams with IMRT plans, and the way in which the physicians
      contoured the lymph nodes. The dose-volume histograms of conventional opposed
      lateral fields were compared with that of the multiple tangential EF-IMRT fields.
      IMRT plans with neck nodes contoured up to and including the skin surface were
      compared with plans that contoured the neck nodes 5 mm away from the skin
      surface. In addition, IMRT plans defining the skin as a sensitive structure were
      compared with plans that did not define the skin as a sensitive structure. All
      plans were created using an anthropomorphic Rando phantom, and the skin doses
      were measured with and without the mask. In each measurement, 6 thermoluminescent
      dosimeters (TLDs) were placed at the lateral and medial surfaces of the neck.
      RESULTS: For all four plans, the measured skin doses with the mask were
      consistently higher than those without the mask. The average dose increase was
      about 18% owing to the bolus effect of the mask. Multiple tangential fields used
      in IMRT plans contributed to an increase in skin dose by about 19% and 27%, with
      and without the mask, respectively. If the skin of the neck was contoured as a
      sensitive structure for dose optimization, the volume of skin that received >45
      Gy was further reduced by about 20%. Five patients immobilized with head and
      shoulder masks were treated with EF-IMRT plans with the neck nodes carefully
      delineated away from the skin surface. The neck skin was identified as a
      sensitive structure for dose optimization. Grade 1 toxicity was observed in 3
      patients, Grade 2 in 1 patient, and Grade 3 in 1 patient toward the end of
      treatment. CONCLUSION: Multiple factors contributed to the observed acute skin
      reaction for head-and-neck cancer patients treated with EF-IMRT. By taking into
      consideration the skin as a sensitive structure during inverse planning, it was
      possible to reduce the skin dose to a tolerable level without compromising tumor
      target coverage.

PMID- 12062607
TI  - Intensity-modulated radiotherapy versus conventional three-dimensional conformal
      radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.
AB  - PURPOSE: To compare intensity-modulated radiotherapy (IMRT) and conventional
      three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new
      onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally
      recurrent NPC. METHODS AND MATERIALS: Between January 14 and February 23, 2000, 5
      field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using
      the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung,
      Taiwan. The planning data of these patients were later transferred to Memorial
      Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation
      fields were created for each patient using an inverse treatment planning system.
      The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship
      between the anatomic shapes and locations of targets and the results of different
      plans were studied. RESULTS: Target doses were more homogeneous in IMRT plans.
      The average maximal brainstem dose (D(05), the dose received by 5% of the
      brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to
      15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003,
      respectively, compared with 3D-CRT, paired Student's t test). Five anatomic
      factors were found that predicted greater benefits with IMRT. These factors were
      (1) vertical length of target >7 cm, (2) minimal distance between target and
      brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4)
      maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of
      target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic
      factors, the benefits achieved by IMRT planning would have been greater than the
      benefits for the other 7 patients (p = 0.005, Fisher's exact test). CONCLUSION:
      For boost or salvage treatment of NPC, lower normal tissue doses and more
      homogeneous target doses were achieved with IMRT plans. For NPC patients with at
      least 1 of the 5 anatomic factors, IMRT is highly recommended.

PMID- 12062608
TI  - Long-term survival of nasopharyngeal carcinoma patients treated with adjuvant
      chemotherapy subsequent to conventional radical radiotherapy.
AB  - PURPOSE: To assess the long-term survival of patients with nasopharyngeal
      carcinoma (NPC) who were treated with conventional radical radiotherapy (RT)
      followed by adjuvant chemotherapy. METHODS AND MATERIALS: Ninety-one newly
      diagnosed patients with Stage III and IV (American Joint Committee on Cancer,
      1988) NPC, seen at the University of Malaya Medical Center, Kuala Lumpur,
      Malaysia between January 1992 and May 1997, were treated with RT followed by
      adjuvant chemotherapy. The tumor dose was 70 Gy delivered in 35 fractions, 5
      fractions weekly. Three cycles of chemotherapy, each consisting of 5
      fluorouracil, 1 g/m(2)/d on Days 1-4 and cisplatin 100 mg/m(2) on Day 1, were
      administered 3 weeks after RT completion. Thirty-six patients had Stage II, 10
      had Stage III, and 45 had Stage IV disease (AJCC 1997 staging system). RESULTS:
      After a median follow-up of 61 months, the 5-year overall survival rate for all
      91 patients was 80.1%, the disease-free survival rate was 76%, and the
      locoregional control rate was 85%. The 3-year overall survival rate for Stage II
      was 94.3%; it was 80% for Stage III and 79.8% for Stage IV (p = 0.0108). The 3
      year DFS rate for Stage II was 90%; it was 80% for Stage II and 65% for Stage IV.
      The rate of distant failure for Stage IV was 8.9%. CONCLUSION: Radical RT
      followed by adjuvant chemotherapy was effective in our patients with
      locoregionally advanced NPC. The long-term results appear encouraging, even for
      patients with Stage IV disease. This single institution experience deserves
      further investigation in prospective trials.

PMID- 12062609
TI  - Trimodal combination therapy for maxillary sinus carcinoma.
AB  - PURPOSE: This study was conducted to evaluate the effectiveness of trimodal
      combination therapy (radiotherapy, intra-arterial chemotherapy, antrotomy) for
      the treatment of primary maxillary sinus carcinoma. METHODS AND MATERIALS:
      Between 1977 and 1996, 110 patients with maxillary squamous cell carcinoma were
      treated with trimodal combination therapy at Tokyo Medical and Dental University
      Hospital. All tumors were classified according to the 1997 UICC TNM staging
      system. Eighty percent of patients had T3 or T4 tumors. The T3 and T4 tumors were
      also classified into three groups according to their location, as visualized
      using computed tomography: the posterior-lateral (P) group, the medial (M) group,
      and the upper (U) group. Eight patients received additional radiotherapy, and 37
      patients underwent a second surgical procedure, in addition to the trimodal
      combination therapy. RESULTS: The 5-year cause-specific survival and local
      control rates were 71% and 65%, respectively. The 5-year local control rate was
      80% for the T1+2 tumors, 64% for the T3 tumors, and 52% for the T4 tumors (p =
      0.06). Patients in the P+M group who received a 5-fluorouracil (5-FU) dosage of
      more than 3500 mg had a better 5-year local control rate than patients who
      received a 5-FU dosage of less than 3500 mg (p = 0.01). No improvement in the
      local control rate after a second surgical procedure or additional irradiation
      treatment was observed in any of the groups. CONCLUSION: Trimodal combination
      therapy provides good local control, with the final outcome depending on the T
      stage of the tumor and the dosage of 5-FU.

PMID- 12062610
TI  - Does downstaging predict improved outcome after preoperative chemoradiation for
      extraperitoneal locally advanced rectal cancer? A long-term analysis of 165
      patients.
AB  - PURPOSE: To evaluate the impact of tumor response; tumor and nodal downstaging;
      and cTNM, yTNM (clinical stage after chemoradiation, based on preoperative
      imaging), and pTNM classifications on long-term outcome in patients with rectal
      cancer treated with preoperative 5-fluorouracil (5-FU)-based concurrent
      chemoradiation. METHODS AND MATERIALS: Between January 1990 and March 1998, 165
      consecutive patients with locally advanced extraperitoneal cancer of the rectum
      were treated with preoperative chemoradiation. Four patients had a cT2 lesion
      (2.5%), 120 had a cT3 lesion (74.5%), and 41 had a cT4 lesion (23%). The nodal
      involvement at combined imaging was cN0 in 21%, cN1 in 41%, cN2 in 34%, and cN3
      in 4%. Preoperative chemoradiation was delivered according to 1 of 3 schedules:
      (1) FUMIR-T3 (from 1990 to 1995) for patients with cT3N0-2 or cT2N1-2 rectal
      carcinoma (82 patients): 37.8 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days
      1-4, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Day 1; (2) FUMIR-T4
      (from 1990 to 1999) for patients with cT4N0-3 or cT3-4N3 rectal carcinoma (40
      patients): 45 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32,
      continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Days 1 and 29; and (3)
      PLAFUR-4 (from 1995 to 1998) for patients with cT3N0-2 or cT2N1-2 rectal
      carcinoma (42 patients): 50.4 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days
      1-4 and 29-32, continuous infusion, and cisplatin, 60 mg/m(2)/d on Days 1 and 29.
      Four to five weeks after chemoradiation, patients were reevaluated for clinical
      response by imaging studies (CT scan, transrectal ultrasonography, barium enema,
      liver ultrasonography, chest X-rays) and restaged (yTNM). Surgery was performed 6
      8 weeks after chemoradiation. Adjuvant chemotherapy (5-FU + l-folinic acid) was
      delivered to 26 patients in the FUMIR-T4 protocol group. Local control (LC),
      freedom from distant metastases (FDM), disease-free survival, and overall
      survival (OS) were evaluated according to the clinical response and cTNM, yTNM,
      and pTNM classification. The median follow-up was 67 months. RESULTS: The 5-year
      survival rate was 100% for cT2, 77% for cT3, and 62% for cT4 (p = 0.0497); after
      chemoradiation, it ranged between 81% and 91% for pT0-pT2 and dropped to 66% for
      pT3 and 47% for pT4 (p = 0.014). The 5-year local control rate was, at the first
      staging, 84% for cT3 and 72% for cT4; after chemoradiation, the pT stage
      correlated significantly with LC (p = 0.0012): 100% for pT0, 83% for pT1, 88% for
      pT2, 79% for pT3, and 46% for pT4. N stage was statistically significant in
      predicting FDM and OS at any staging step. A significant impact of tumor
      response, tumor downstaging, and nodal downstaging on LC, FDM, disease-free
      survival, and OS was also recorded. If the residual tumor, before surgery, had a
      tumor index <30 (i.e., width less than one-quarter of rectal circumference and
      length in its caudocranial axis < or =30 mm), the 5-year LC, FDM, disease-free
      survival, and OS rates were significantly higher at both the univariate and the
      multivariate analyses. The surgical procedure was tailored according to tumor
      downstaging, and thus the choice of sphincter-preserving surgery was based on the
      distance between the lower pole of the tumor and the anorectal ring "after"
      chemoradiation. In 36 patients with the lower pole of the lesion in the range of
      0-30 mm from the anorectal ring, 16 patients (44%) underwent a sphincter-saving
      procedure. All clinical outcomes were similar compared with 20 patients with
      tumor located at the same rectum level who received an abdominoperineal
      resection. CONCLUSION: After preoperative chemoradiation, clinical response and
      tumor/nodal pathologic downstaging showed a close correlation with improved
      outcomes. The better 5-year survival and local control in pT0-2 patients
      regardless of their initial stage seems to confirm a heterogeneity in rectal
      cancer patients. The responder population showed a behavior similar to rectal
      cancer diagnosed at Stage cT1-2 and treated with conservative surgery alone.
      Additional studies aimed at improving local tumor response seem justified. Trials
      of sphincter-saving surgery after a major response are warranted.

PMID- 12062611
TI  - A single-institution experience with concurrent capecitabine and radiation
      therapy in gastrointestinal malignancies.
AB  - PURPOSE: We report our clinical experience with 32 patients receiving concurrent
      irradiation and capecitabine. METHODS AND MATERIALS: Medical records of patients
      with gastrointestinal malignancies treated with radiation and capecitabine
      therapy were reviewed. RESULTS: The population consisted of 20 males and 12
      females, with a median age of 67.5 years (45-84 years) and adequate hepatic and
      bone marrow function. Histology was adenocarcinoma in all patients, except two
      with esophageal squamous carcinoma. Twenty-one patients received the regimen as
      adjuvant therapy, three received preoperative therapy, and 8 patients received
      therapy for palliation. The median dose of capecitabine was 1600 mg/m(2)/day
      (1200-2500 mg/m(2)/day) orally for 5 days per week for the duration of radiation
      therapy. Thirty patients received a total dose ranging from 45 Gy to 64 Gy over 4
      6 weeks. Two previously radiated patients received total doses of 29.9 Gy and 46
      Gy. Grade 3/4 toxicities observed were neutropenia in 3 patients and diarrhea,
      thrombocytopenia, fatigue, and myocardial infarction in 1 patient each. No
      treatment-related mortality was observed. Twenty of 21 patients (95.2%) who
      received adjuvant therapy continue to be in complete remission. Four of 11 (36%)
      evaluable patients demonstrated a response. CONCLUSION: Concurrent capecitabine
      and radiation were very well tolerated and warrant further investigation in
      prospective trials.

PMID- 12062612
TI  - Influence of radiation dose on positive surgical margins in women undergoing
      breast conservation therapy.
AB  - PURPOSE: Positive surgical margins adversely influence local tumor control in
      breast conservation therapy (BCT). However, reports have conflicted regarding
      whether an increased radiation dose can overcome this poor prognostic factor. In
      this study, we evaluated the influence of an increased radiation dose on tumor
      control in women with positive surgical margins undergoing BCT. METHODS AND
      MATERIALS: Between 1978 and 1994, 733 women with pathologic Stage I-II breast
      cancer and known surgical margin status were treated at Thomas Jefferson
      University Hospital with BCT. Of these 733 patients, 641 women had a minimal
      tumor bed dose of 60 Gy and had documentation of their margin status; 509 had
      negative surgical margins, and 132 had positive surgical margins before
      definitive radiotherapy. Complete gross excision of the tumor and axillary lymph
      node sampling was obtained in all patients. The median radiation dose to the
      primary site was 65.0 Gy (range 60-76). Of the women with positive margins (n =
      132), the influence of higher doses of radiotherapy was evaluated. The median
      follow-up time was 52 months. RESULTS: The local tumor control rate for patients
      with negative margins at 5 and 10 years was 94% and 88%, respectively, compared
      with 85% and 67%, respectively, for those women with positive margins (p =
      0.001). The disease-free survival rate for the negative margin group at 5 and 10
      years was 91% and 82%, respectively, compared with 76% and 71%, respectively, for
      the positive margin group (p = 0.001). The overall survival rate of women with
      negative margins at 5 and 10 years was 95% and 90%, respectively. By comparison,
      for women with positive surgical margins, the overall survival rate at 5 and 10
      years was 86% and 79%, respectively (p = 0.008). A comparison of the positive and
      negative margin groups revealed that an increased radiation dose (whether entered
      as a dichotomous or a continuous variable) >65.0 Gy did not improve local tumor
      control (p = 0.776). On Cox multivariate analysis, margin status and menopausal
      status had prognostic significance for local tumor control and DFS. CONCLUSION:
      Patients with positive surgical margins have a higher risk of local tumor
      recurrence and worse survival when undergoing BCT. Higher doses of radiation are
      unable to provide an adequate level of local control in patients with positive
      margins.

PMID- 12062613
TI  - Repeat high-dose external beam irradiation for in-breast tumor recurrence after
      previous lumpectomy and whole breast irradiation.
AB  - PURPOSE: To determine whether excision of an in-breast tumor recurrence (IBTR)
      plus 5000 cGy in 25 fractions to the new operative area is both tolerated and
      effective as treatment for an IBTR after previous lumpectomy and whole breast
      irradiation. METHODS AND MATERIALS: Thirty-nine women with an IBTR after
      lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal
      carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy
      (RT), 5000 cGy in 25 fractions, to the operative area using electrons of
      appropriate energy. The interval from completion of the first course of RT to
      diagnosis of the IBTR ranged from 16 to 291 months (median 63). RESULTS: The
      repeat course of RT to the new operative area was well tolerated in all patients,
      and no late sequelae occurred other than skin pigmentation changes. Eight
      patients, including 2 with suspicious bone scans at the time of IBTR, developed
      distant metastases, and 7 died 21-71 months (median 48) after retreatment. One
      patient was alive with distant metastases at 27 months after retreatment. Four of
      the 8 patients who developed distant metastases also had a second IBTR, and 3
      died with persistent disease in the breast. An additional 4 patients, for a total
      of 8, had a second IBTR. Three were alive and free of disease after mastectomy,
      and 1 was alive and free of disease after mastectomy and additional RT for chest
      wall recurrence. An additional patient developed recurrence in the axilla 9
      months after reirradiation and was treated with surgery; she died free of disease
      at 63 months. One patient underwent mastectomy for suspected persistent disease 2
      months after completion of repeat RT; no evidence of recurrent tumor was found in
      the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at
      death or at last follow-up 1-180 months (median 51.5) after reirradiation. Using
      the Kaplan-Meier life table analysis, the estimated overall and disease-free 5
      year survival rate for the 39 patients was 77.9% and 68.5%, respectively.
      CONCLUSION: For select patients with an IBTR after lumpectomy and breast
      irradiation, excision of the IBTR followed by repeat external beam RT to the
      operative area may be an acceptable alternative to mastectomy.

PMID- 12062614
TI  - Extramedullary plasmacytoma: clinical and histopathologic study.
AB  - PURPOSE: To review the histories of extramedullary plasmacytoma patients
      diagnosed in Slovenia between 1969 and 1999, to determine the relationship
      between radiotherapy (XRT) dose and local tumor control, and to clarify the role
      of elective nodal XRT and the prognostic value of Bartl's histologic grading
      criteria (originally devised for multiple myeloma [MM]). METHODS AND MATERIALS:
      The database of the Cancer Registry of Slovenia was used for the identification
      of patients. The inclusion criteria were as follows: bone marrow biopsy showing
      less than 10% plasma cells, normal skeletal survey, and immunohistochemically
      determined tumor monoclonality. Simulation/portal films were reviewed to assess
      the extent of elective nodal XRT. RESULTS: Twenty-six patients with 31 tumors
      fulfilled the inclusion criteria. In 4 patients, nine metachronously appearing
      solitary tumors were diagnosed. The head-and-neck region and other body sites
      were the sites of origin of primary tumors in 84% and 16% of patients,
      respectively, whereas in the two regions, regional disease was seen in 15% and
      60% of patients, respectively. Therapy was as follows: XRT, 12 patients; surgery
      and postoperative XRT, 15 patients; and surgery, 4 patients. Ultimate local and
      regional control rates were 90% and 97%, respectively, and MM developed in 2 (8%)
      patients. The 10-year disease-specific and overall survival rates were 87% and
      61%, respectively. The analysis of the dose-effect relationship showed that more
      conservative treatment is justified: for macroscopic disease, 40-50 Gy (2
      Gy/day), adjusted to the bulk of disease; for microscopic disease, 36-40 Gy;
      after R0 surgery, no XRT is required, but close observation is needed. No
      attempts should be made to treat uninvolved nodal regions. Using Bartl's
      histologic grading criteria, trends were detected in patients with higher tumor
      grades: regional lymph node involvement (p = 0.04) and shorter disease-specific
      survival (p = 0.08). CONCLUSIONS: Extramedullary plasmacytoma is a highly curable
      disease when XRT is used with or without previous surgery. The rate of conversion
      to MM is low. Moderate-dose XRT using limited fields is recommended. The
      prognostic value of Bartl's grading system needs further evaluation.

PMID- 12062615
TI  - Two fractions of high-dose-rate brachytherapy in the management of cervix cancer:
      clinical experience with and without chemotherapy.
AB  - PURPOSE: In recent years, high-dose-rate brachytherapy has become popular in the
      management of carcinoma of the uterine cervix, because it eliminates many of the
      problems associated with low-dose-rate brachytherapy. However, the optimum time
      dose-fractionation remains controversial. Two fractions of high-dose-rate
      brachytherapy are convenient for patients, but most radiation oncologists in the
      United States do not use them, because of fear that they could lead to excessive
      rectal or bladder toxicity. Here we present our experience, which suggests that a
      two-fraction regimen is indeed safe and effective. METHODS: We treated 49
      patients with Stages I-III biopsy-proven carcinoma of the uterine cervix by
      external beam radiation therapy (EBRT), plus two fractions of high-dose-rate
      brachytherapy. The histology was squamous cell carcinoma in 43 patients (88%) and
      nonsquamous in 6 (12%). The median size of the primary tumor was 6 cm (range: 3
      10 cm). Each patient received EBRT to the pelvis to a median dose of 45 Gy
      (range: 41.4-50.4 Gy), followed by a parametrial boost when indicated. Thirty
      patients (61%) also received irradiation to the para-aortic lymph nodes to a dose
      of 45 Gy. After EBRT, each patient underwent two applications of high-dose-rate
      brachytherapy, 1 week apart. The dose delivered to point A was 9 Gy per
      application for 49 applications (50%) and 9.4 Gy for 43 applications (44%), and
      it varied from 7 to 11 Gy for the rest (6%). The total dose to the rectum from
      both high-dose-rate brachytherapy applications ranged from 4.7 to 11.7 Gy
      (median: 7.1 Gy), and the total dose to the bladder from 3.8 to 15.5 Gy (median:
      10.5 Gy). Twenty-five of the 49 patients (51%) received concomitant chemotherapy
      (cisplatin 20 mg/m(2)/day for 5 days) during the first and fourth weeks of EBRT
      and once after the second high-dose-rate brachytherapy application. Chemotherapy
      was not assigned in a randomized fashion. The use of chemotherapy increased
      during the time period spanned by this study as increasing evidence supporting
      the use of chemotherapy began to appear. RESULTS: The observed survival rates
      after 2, 3, and 5 years were 83%, 78%, and 78%, respectively. The surviving
      patients have been followed up for a median of 3 years (range: 2-6 years). Eight
      of the 49 patients suffered local failures. Among patients treated without
      chemotherapy, the 3-year local control rate was 77%; it was 88% among those
      receiving chemotherapy. There have been no regional failures. Four patients
      developed distant metastases. At 3 years, 91% of the patients in each group were
      free of distant metastases. Ten of the 49 patients (20%) suffered Grade 3 acute
      toxicity; 11 (22%) had Grade 4. Among the 24 patients treated without
      chemotherapy, only 1 (4%) suffered Grade 3 toxicity. Among the 25 patients
      receiving chemotherapy, in contrast, 8 (32%) suffered Grade 3 and 12 (48%) Grade
      4 acute toxicity. Only 2 patients suffered late toxicity: One suffered Grade 2
      and the other Grade 3 late toxicity. The actuarial risk of Grade 2 or worse late
      toxicity was 5%, with or without chemotherapy. CONCLUSIONS: Our experience
      suggests that two fractions of high-dose-rate brachytherapy are safe and
      effective in the management of cervix cancer, even in conjunction with
      concomitant cisplatin. The fears that the use of two fractions would lead to
      excessive rectal or bladder toxicity proved unfounded. Guidelines for ensuring a
      low complication rate are discussed.

PMID- 12062617
TI  - Acute vasculitis after endovascular brachytherapy.
AB  - PURPOSE: Angioplasty effectively relieves coronary artery stenosis but is often
      followed by restenosis. Endovascular radiation (beta or gamma) at the time of
      angioplasty prevents restenosis in a large proportion of vessels in swine (short
      term) and humans (short and long term). Little information is available about the
      effects of this radiation exposure beyond the wall of the coronary arteries.
      METHODS AND MATERIALS: Samples were obtained from 76 minipigs in the course of
      several experiments designed to evaluate endovascular brachytherapy: 76 of 114
      coronary arteries and 6 of 12 iliac arteries were exposed to endovascular
      radiation from 32P sources (35 Gy at 0.5 mm from the intima). Two-thirds of the
      vessels had angioplasty or stenting. The vessels were systematically examined
      either at 28 days or at 6 months after radiation. RESULTS: We found an unexpected
      lesion: acute necrotizing vasculitis in arterioles located < or =2.05 mm from the
      target artery. It was characterized by fibrinoid necrosis of the wall, often
      associated with lymphocytic exudates or thrombosis. Based on the review of
      perpendicular sections of tissue samples, the arterioles had received between 6
      and 40 Gy. This arteriolar vasculitis occurred at 28 days in samples from 51% of
      irradiated coronary arteries and 100% of irradiated iliac arteries. By 6 months,
      the incidence of acute vasculitis decreased to 24% around the coronary arteries.
      However, at that time, healing vasculitis was evident, often with luminal
      narrowing, in 46% of samples. Vasculitis was not seen in any of 44 samples from
      unirradiated vessels (0%) and had no relation to angioplasty, stenting, or their
      sequelae. This radiation-associated vasculitis in the swine resembles the
      localized lymphocytic vasculitis that we have reported in tissues of humans
      exposed to external radiation. On the other hand, it is quite different from the
      various types of systemic vasculitis that occur in nonirradiated humans.
      CONCLUSION: Endoarterial brachytherapy using 32P results in vascular effects
      beyond the adventitia of the target vessel. This necrotizing vasculitis is
      causally related to radiation, but its mechanism is unclear and a dose effect is
      not evident. Quite possibly, local upregulation of inflammatory cytokines
      contributes to this radiation-associated vasculitis, which only involved some of
      the arterioles in each sample. It is likely that radiation-associated vasculitis
      also occurs around human coronary arteries and may result in foci of ischemia. To
      our knowledge, this lesion has not been previously recognized, either in
      experimental models or in human specimens examined after
      angioplasty/brachytherapy.

PMID- 12062616
TI  - Intravaginal high-dose-rate brachytherapy for Stage IB (FIGO Grade 1, 2)
      endometrial cancer.
AB  - PURPOSE: To evaluate the outcome of patients with Stage IB Grades 1 and 2
      endometrial cancer treated with adjuvant high-dose-rate intravaginal
      brachytherapy. METHODS AND MATERIALS: Between November 1987 and October 1999, 233
      patients with Stage IB FIGO Grades 1 and 2 were treated with postoperative
      adjuvant high-dose-rate intravaginal brachytherapy. The median dose was 21 Gy in
      7 Gy/fraction given at 2-week intervals. The mean age was 60 years. All patients
      underwent simple hysterectomy. Comprehensive surgical staging, defined as pelvic
      washing and pelvic and paraaortic lymph nodes sampling, was done in 9% of
      patients. Patients with FIGO Grade 3, papillary serous cancer, or clear-cell
      cancer were excluded from this analysis. Complications were assessed in terms of
      late Radiation Therapy Oncology Group toxicity (Grade > or =3) of the
      gastrointestinal tract, genitourinary tract, and vagina. RESULTS: With a median
      follow-up of 57 months, the 5-year vaginal/pelvic control, disease-free survival,
      and overall survival rate was 96% (95% confidence interval [CI] 94-99%), 94% (95%
      CI 91-98%), and 94% (95% CI 91-98%), respectively. The influence on outcome of
      age, grade (1 vs. 2), depth of invasion (one-third or less or greater than one
      third), capillary space-like invasion, lower uterine segment involvement, and
      comprehensive surgical staging was evaluated. None of these factors significantly
      affected the rate of vaginal/pelvic control. Only age > or =60 years influenced
      the outcome for disease-free and overall survival. The 5-year rate for both
      disease-free and overall survival was 90% (95% CI 84-97%) for patients > or =60
      years old compared with 99% (95% CI 96-100%) for those <60 years (p = 0.03 and
      0.005, respectively). Of 233 patients, 3 (1%) developed Grade 3 or greater
      complications, with a 5-year actuarial rate of 2% (95% CI 0-5%). Two patients
      developed Grade 3 genitourinary toxicity, and 1 Grade 4 vaginal toxicity.
      CONCLUSION: On the basis of this retrospective study, adjuvant postoperative high
      dose-rate intravaginal brachytherapy provides excellent outcomes and acceptable
      morbidity. These results compare very favorably with those reported in the
      literature using surgery alone or with pelvic radiation.

PMID- 12062618
TI  - Radiation oncologists in 2000: demographic, professional, and practice
      characteristics.
AB  - PURPOSE: To describe the demographic, professional, and practice characteristics
      of radiation oncologists, emphasizing comparisons to data from a similar 1995
      Survey. METHODS AND MATERIALS: In spring 2000, we surveyed 603 randomly selected
      radiation oncologists by mail, using a one-page questionnaire-455 responded. We
      weighted responses to make answers representative of all radiation oncologists in
      the United States. RESULTS: Approximately 45% of post-training, professionally
      active, radiation oncologists were <45 years old and 22% were women. Forty-two
      percent of radiation oncologists in training were women. Thirty-three percent of
      radiation-oncology-only practices were solo practices. The greatest percentage of
      post-training, professionally active, radiation oncologists were in nonacademic
      private radiation oncology practices. Fifty-three percent of post-training,
      professionally active, radiation oncologists reported that their workload was
      about right. Eighteen percent of individuals 60-64 years old and approximately
      two-thirds of those > or =65 years old were not working (retired). The full-time
      equivalency of those aged 55-74 fell by 12 percentage points between 1995 and
      2000. CONCLUSIONS: Most demographic, professional, and practice characteristics
      remained relatively constant between 1995 and 2000, with the exception of work
      status patterns. Radiation oncologists reported a more balanced workload than
      that reported by diagnostic radiologists. The surplus of radiation oncologists,
      which was predicted in the mid-1990s, was not demonstrated.

PMID- 12062619
TI  - The relationship between educational preparation and performance on the ARRT
      examination in radiation therapy.
AB  - PURPOSE: To determine if graduates of different types of educational programs
      obtain similar scores on the Examination in Radiation Therapy administered by the
      American Registry of Radiologic Technologists. The results will help inform
      discussions regarding educational requirements for radiation therapists. METHODS
      AND MATERIALS: Test scores were obtained for 531 candidates who had taken the
      examination for the first time in 1997, 1998, or 1999. Candidates were divided
      into the following three categories, based on the type of educational program
      attended: hospital-based certificate, associate's degree, or bachelor's degree.
      To determine if test scores were related to the type of educational preparation,
      analyses of variance were conducted separately to test for differences in total
      scores and section scores, and scores on test questions intended to measure
      critical thinking skills. RESULTS: Candidates with an associate's degree scored
      slightly lower than candidates with a bachelor's degree on the total test (p <
      0.10) and lower than candidates with either a certificate or bachelor's degree on
      Section B of the examination (Treatment Planning and Delivery, p < 0.10).
      Baccalaureate candidates did not obtain higher scores than those prepared in
      certificate programs. On critical thinking questions, candidates with
      certificates scored higher than those with associate's degrees (p < 0.10). Some
      evidence suggested that candidates with a certificate scored higher on critical
      thinking than those with a bachelor's degree (p < 0.10), and that candidates with
      a bachelor's degree scored higher than candidates with an associate's degree (p <
      0.10). CONCLUSIONS: Although some of the differences in the mean test scores
      among the three educational groups were statistically significant, all
      differences were small and do not support one type of educational preparation
      over another.

PMID- 12062620
TI  - Radioprotective action of curcumin extracted from Curcuma longa LINN: inhibitory
      effect on formation of urinary 8-hydroxy-2'-deoxyguanosine, tumorigenesis, but
      not mortality, induced by gamma-ray irradiation.
AB  - PURPOSE: We evaluated the radioprotective action of curcumin [1,7-bis(4-hydroxy-3
      methoxyphenyl)-1,6-heptadiene-3,5-dione] extracted from Curcuma longa LINN
      against the acute and chronic effects and the mortality induced by exposure to
      radiation using female rats. METHODS AND MATERIALS: For the assay of 8-hydroxy-2'
      deoxyguanosine (8-OHdG) in urine, a marker for acute effects, Wistar-MS virgin
      rats were fed the basal diet with exposure at 0 or 3 Gy to gamma-rays from a 60Co
      source as the control. Rats in the experimental groups received whole-body
      irradiation with 3 Gy and were fed a diet containing 1% (wt/wt) curcumin for 3
      days before and/or 2 days after irradiation. The urine was collected for a 24-h
      period between 1 and 2 days after irradiation. Urine samples were used to
      determine the 8-OHdG level using an enzyme-linked immunosorbent assay and the
      creatinine level by a modified Jaffe reaction. For long-term effects, rats at Day
      17 of pregnancy were fed a diet containing curcumin for 3 days before and/or 3
      days after irradiation with 1.5 Gy, and received a pellet of diethylstilbestrol
      as the promoter. The rats were examined for mammary and pituitary tumors for 1
      year. To determine survival, virgin rats received whole-body irradiation with 9.6
      Gy and were fed a diet containing curcumin for 3 days before and/or 3 days after
      irradiation. After irradiation, all rats were assessed daily for survival for 30
      days. RESULTS: Acutely in virgin rats irradiated with 3 Gy, the creatinine
      corrected concentration and total amount of 8-OHdG in the 24-h urine samples were
      higher (approximately 1.3-fold) than the corresponding values in the
      nonirradiated controls. Adding curcumin to the diet for 3 days before and/or 2
      days after irradiation reduced the elevated 8-OHdG levels by 50-70%. The
      evaluation of the protective action of curcumin against the long-term effects
      revealed that curcumin significantly decreased the incidence of mammary and
      pituitary tumors. However, the experiments on survival revealed that curcumin was
      not effective when administered for 3 days before and/or 3 days after irradiation
      (9.6 Gy). CONCLUSION: These findings demonstrate that curcumin can be used as an
      effective radioprotective agent to inhibit acute and chronic effects, but not
      mortality, after irradiation.

PMID- 12062621
TI  - Differential oxygen dynamics in two diverse Dunning prostate R3327 rat tumor
      sublines (MAT-Lu and HI) with respect to growth and respiratory challenge.
AB  - PURPOSE: Since hypoxia may influence tumor response to therapy and prognosis, we
      have compared oxygenation of tumors known to exhibit differential growth rate and
      tissue differentiation. METHODS AND MATERIALS: Regional tumor oxygen tension was
      measured using 19F nuclear magnetic resonance echo planar imaging relaxometry of
      hexafluorobenzene, which provided dynamic maps with respect to respiratory
      intervention. Investigations used two Dunning prostate R3327 rat tumor sublines:
      the fast growing, highly metastatic MAT-Lu and the moderately well
      differentiated, slower growing HI. RESULTS: Both sublines showed significantly
      higher oxygen tension in smaller tumors (<2 cm(3)) than in larger tumors (>3.5
      cm(3)). Pooled data showed that MAT-Lu tumors exhibited greater hypoxia compared
      with the size-matched HI tumors (p < 0.0001). Respiratory challenge (oxygen or
      carbogen) produced significant increases in mean pO(2) for tumors of both
      sublines (p < 0.0001). However, initially hypoxic regions displayed very
      different behavior in each subline: those in the HI tumors responded rapidly with
      significant elevation in pO(2), while those in the MAT-Lu tumors showed little
      response to respiratory intervention. CONCLUSIONS: These results concur with
      hypotheses that hypoxia is related to tumor growth rate and degree of
      differentiation. Under baseline conditions, the differences were subtle. However,
      response to respiratory intervention revealed highly significant differences,
      which, if held valid in the clinic, could have prognostic value.

PMID- 12062623
TI  - Improving the consistency in cervical esophageal target volume definition by
      special training.
AB  - PURPOSE: Three-dimensional conformal radiation therapy requires the precise
      definition of the target volume. Its potential benefits could be offset by the
      inconsistency in target definition by radiation oncologists. In a previous survey
      of radiation oncologists, a large degree of variation in target volume definition
      of cervical esophageal cancer was noted for the boost phase of radiotherapy. The
      present study evaluated whether special training could improve the consistency in
      target volume definitions. METHODS AND MATERIALS: A pre-training survey was
      performed to establish baseline values. This was followed by a special one-on-one
      training session on treatment planning based on the RTOG 94-05 protocol to 12
      radiation oncologists. Target volumes were redrawn immediately and at 1-2 months
      later. Post-training vs. pre-training target volumes were compared. RESULTS:
      There was less variability in the longitudinal positions of the target volumes
      post-training compared to pre-training (p < 0.05 in 5 of 6 comparisons). One case
      had more variability due to the lack of a visible gross tumor on CT scans.
      Transverse contours of target volumes did not show any significant difference pre
      or post-training. CONCLUSION: For cervical esophageal cancer, this study
      suggests that special training on protocol guidelines may improve consistency in
      target volume definition. Explicit protocol directions are required for
      situations where the gross tumor is not easily visible on CT scans. This may be
      particularly important for multicenter clinical trials, to reduce the occurrences
      of protocol violations.

PMID- 12062622
TI  - MRI simulation: effect of gradient distortions on three-dimensional prostate
      cancer plans.
AB  - PURPOSE: To quantify the dosimetric consequences of external patient contour
      distortions produced on low-field and high-field MRIs for external beam radiation
      of prostate cancer. METHODS AND MATERIALS: A linearity phantom consisting of a
      grid filled with contrast material was scanned on a spiral CT, a 0.23 T open MRI,
      and a 1.5 T closed bore system. Subsequently, 12 patients with prostate cancer
      were scanned on CT and the open MRI. A gradient distortion correction (GDC)
      program was used to postprocess the MRI images. Eight of the patients were also
      scanned on the 1.5 T MRI with integrated GDC correction. All data sets were fused
      according to their bony landmarks using a chamfer-matching algorithm. The
      prostate volume was contoured on an MRI image, irrespective of the apparent
      prostate location in those sets. Thus, the same target volume was planned and
      used for calculating the anterior-posterior (AP) and lateral separations. The
      number of monitor units required for treatment using a four-field conformal
      technique was compared. Because there are also setup variations in patient outer
      contours, two different CT scans from 20 different patients were fused, and the
      differences in AP and lateral separations were measured to obtain an estimate of
      the mean interfractional separation variation. RESULTS: All AP separations
      measured on MRI were statistically indistinguishable from those on CT within the
      interfractional separation variations. The mean differences between CT and low
      field MRI and CT and high-field MRI lateral separations were 1.6 cm and 0.7 cm,
      respectively, and were statistically significantly different from zero. However,
      after the GDC was applied to the low-field images, the difference became 0.4 +/-
      0.4 mm (mean +/- standard deviation), which was statistically insignificant from
      the CT-to-CT variations. The mean variations in the lateral separations from the
      low-field images with GDC would result in a dosimetric difference of <1%,
      assuming an equally weighted four-field 18-MV technique for patient separations
      up to approximately 40 cm. CONCLUSIONS: For patients with lateral separations <40
      cm, a homogeneous calculation simulated using a 1.5 T MRI or a 0.23 T MRI with a
      gradient distortion correction will yield a monitor unit calculation
      indistinguishable from that generated using CT simulation.

PMID- 12062624
TI  - Comparison of methods for calculating rectal dose after (125)I prostate
      brachytherapy implants.
AB  - PURPOSE: To compare several different methods of calculating the rectal dose and
      examine how accurately they represent rectal dose surface area measurements and,
      also, their practicality for routine use. METHODS AND MATERIALS: This study
      comprised 55 patients, randomly selected from 295 prostate brachytherapy patients
      implanted at the Vancouver Cancer Center between 1998 and 2000. All implants used
      a nonuniform loading of 0.33 mCi (NIST-99) 125I seeds and a prescribed dose of
      144 Gy. Pelvic CT scans were obtained for each patient approximately 30 days
      after implantation. For the purposes of calculating the rectal dose, several
      structures were contoured on the CT images: (1) a 1-mm-thick anterior rectal
      wall, (2) the anterior half rectum, and (3) the whole rectum. Point doses were
      also obtained along the anterior rectal surface. The thin wall contour provided a
      surrogate for a dose-surface histogram (DSH) and was our reference standard
      rectal dose measurement. Alternate rectal dose measurements (volume, surface
      area, and length of rectum receiving a dose of interest [DOI] of > or =144 Gy and
      216 Gy, as well as point dose measures) were calculated using several methods
      (VariSeed software) and compared with the surrogate DSH measure (SA(DOI)).
      RESULTS: The best correlation with SA(144 Gy) was the dose volumes (whole or
      anterior half rectum) (R = 0.949). The length of rectum receiving > or =144 Gy
      also correlated well with SA(144 Gy) (R > or =0.898). Point dose measures, such
      as the average and maximal anterior dose, correlated poorly with SA(144 Gy) (R <
      or =0.649). The 216-Gy measurements supported these results. In addition, dose
      volume measurements were the most practical (approximately 6 min/patient), with
      our surrogate DSH the least practical (approximately 20 min/patient). CONCLUSION:
      Dose-volume measurements for the whole or anterior half rectum, because they were
      the most practical measures and best represented the DSH measurements, should be
      considered a standard method of reporting the rectal dose when calculating the
      DSH is not practical. Average or maximal anterior rectal doses are not reliable
      indicators of surface area dosimetry.

PMID- 12062625
TI  - In regard to Mose et al., IJROBP 2001;51:1328-1335.

PMID- 12062627
TI  - In regard to the radiotherapy of myxopapillary ependymomas.

PMID- 12062628
TI  - Cellular and Molecular Mechanisms of Alcoholic Hepatitis. Proceedings of a
      satellite symposium. Montreal, Quebec, Canada. June 2001.

PMID- 12062629
TI  - Cellular and molecular mechanisms of alcoholic hepatitis: introduction and
      summary of the symposium.
AB  - The National Institute on Alcohol Abuse and Alcoholism and the Office of Rare
      Diseases, National Institutes of Health, sponsored a satellite symposium on
      "Cellular and Molecular Mechanisms of Alcoholic Hepatitis" at the 24th Annual
      Scientific Meeting of the Research Society on Alcoholism, Montreal, Quebec,
      Canada, June 2001. Alcohol intake is a major cause of hepatitis that may lead to
      alcoholic cirrhosis-a major cause of death in the United States. In up to one
      third of heavy drinkers alcoholic hepatitis develops, which is characterized by
      liver cell death and infiltration of leukocytes in hepatic parenchyma. Although
      leukocytes have been implicated in the pathogenesis of alcoholic hepatitis, the
      underlying cellular and molecular mechanisms by which leukocytes migrate to
      hepatic parenchyma and initiate tissue injury are not clear. For this symposium,
      10 speakers were invited to address the following aspects of the mechanisms of
      alcoholic hepatitis: role of Kupffer cells in initiating the process of alcoholic
      hepatitis; types of leukocytes involved in the pathogenesis of alcoholic
      hepatitis; chemokines that are responsible for the attraction of leukocytes;
      adhesion molecules that promote the attachment of leukocytes to the endothelial
      cells and hepatocytes; mechanisms of leukocyte transmigration to hepatic
      parenchyma; mechanisms by which leukocytes initiate tissue injury; and
      interactive effects of alcohol and hepatitis viral proteins on liver injury. This
      article provides an introduction to the problem and a summary of the 10
      scientific presentations delivered at the symposium.

PMID- 12062630
TI  - Liver disease in alcohol abusers: clinical perspective.
AB  - Alcoholic liver disease remains one of the most common causes of chronic liver
      disease in the world. The severity of liver damage related to alcohol varies
      among different individuals and even within any given individual at different
      times. Certain symptoms, signs, and abnormal findings on laboratory tests help
      clinicians distinguish among the various stages of alcohol-induced liver damage
      and, thus, have some prognostic significance. However, because all stages of this
      disease can persist for decades without causing overt evidence of serious liver
      damage, liver biopsy is the only test that can reliably distinguish among the
      various stages of alcohol-induced liver damage in many patients. The therapy of
      alcohol-induced liver disease varies according to the severity of histologic
      liver damage and clinically overt portal hypertension and hepatic dysfunction.
      Abstinence from alcohol consumption improves the clinical outcome of all stages
      of alcoholic liver disease. However, only two agents have proved to lessen early
      mortality in patients who require hospitalization for acutely decompensated
      alcoholic liver disease. It is not known whether either of these agents or other
      treatments prevent the development of alcohol-induced cirrhosis or improve the
      survival of patients who have already developed cirrhosis.

PMID- 12062631
TI  - Role of Kupffer cells in alcoholic hepatitis.
AB  - Kupffer cells play a major role in alcoholic liver disease. Oxidative stress and
      endotoxin are major mediators of the inflammatory process in alcoholic hepatitis.
      Recent evidence supports the suggestion that endotoxin-induced signal
      transduction begins with CD14-mediated activation of Toll-receptor 4 and
      subsequent activation of nuclear factor-kappa B (NF-kappa B) binding activity.
      Free radicals from reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      oxidase in Kupffer cells also activate NF-kappa B binding activity. Inflammatory
      cytokines and cyclooxygenase-2 are up-regulated in response to binding of NF
      kappa B. A combined role for tumor necrosis factor-alpha (TNF-alpha) and
      cyclooxygenase-2 is important in the pathogenesis of alcoholic hepatitis.

PMID- 12062633
TI  - Neutrophil-mediated tissue injury in alcoholic hepatitis.
AB  - The presence of polymorphonuclear leukocytes (neutrophils) in liver parenchyma is
      a prominent feature of alcoholic hepatitis. However, the pathophysiological
      importance of these phagocytes and potential injury mechanisms in alcoholic
      hepatitis remain unclear. This review summarizes the current knowledge on basic
      mechanisms of neutrophil-induced liver injury as it emerged from studying a
      number of different experimental models. This general concept of neutrophil
      mediated liver cell injury agrees with many observations made by examining liver
      sections obtained from patients with alcoholic hepatitis. These include the
      presence of extravasated neutrophils in the liver, evidence for degranulation of
      neutrophils in the parenchyma, and excessive formation of neutrophil
      chemoattractants such as CXC chemokines in liver cells. Colocalization and a
      strong quantitative correlation between apoptotic hepatocytes and neutrophils
      could indicate apoptosis-induced transmigration of neutrophils during alcoholic
      hepatitis, similar to events previously demonstrated in experimental models.
      Furthermore, circulating neutrophils are primed for reactive oxygen species and
      inflammatory mediator formation. However, clear evidence for a neutrophil-induced
      injury in alcoholic hepatitis is missing. Unfortunately, most experimental models
      of alcoholic liver disease do not have a prominent neutrophilic infiltrate.
      Therefore, a high priority of future research has to be to develop an
      experimental model that realistically mimics the neutrophil component of
      alcoholic hepatitis in human beings. This would allow investigators to test the
      concept that neutrophils are important for cell injury during alcoholic hepatitis
      and to identify potential therapeutic intervention strategies.

PMID- 12062632
TI  - Neutrophilic infiltration in alcoholic hepatitis.
AB  - Leukocyte infiltration in the liver is one of the most important features of
      alcoholic liver disease. However, in alcoholic hepatitis, the role of
      polymorphonuclear neutrophils (PMNs) in liver injury still remains to be fully
      elucidated. Furthermore, the migration of PMNs and their presence in the liver
      during alcoholic hepatitis have not been fully investigated. Up-regulation of
      chemokine secretion and adhesion molecule expression on effector cells (i.e.,
      PMNs) and target cells (i.e., hepatocytes) are important factors in neutrophilic
      infiltration of the liver. The CXC chemokines--that is, interleukin (IL)-8 (in
      human beings), cytokine-induced neutrophil chemoattractant (CINC) (in rats), and
      KC (in mice)--are proneutrophilic agents. They are up-regulated during chronic-
      that is, several years of--alcohol use in human beings and in up to 30 weeks in
      experimental models of ethanol intoxication in mice and rats. Up-regulation of
      these chemokines in the circulation and tissues is also associated with enhanced
      neutrophilic infiltration in the liver. In the rat, the up-regulation of CXC
      chemokine production is time dependent. For example, after 16 weeks of feeding,
      up-regulation of CXC chemokine is observed, whereas after 32 weeks, CC chemokines
      are enhanced. Concomitantly, selective migration of PMNs and mononuclear cells is
      observed. In another model, in which both CXC and CC chemokines were enhanced
      after chronic ethanol use for 12 weeks in mice, neutrophilic and
      mononuclear/lymphocytic infiltrations were also seen. This model correlates
      closely with alcoholic hepatitis in human beings, characterized by increased IL
      8, RANTES (regulated upon activation, normal T cell expressed and secreted), and
      macrophage inflammatory protein-1 (MIP-1) and profound increases in neutrophils
      and lymphocytes in the liver.

PMID- 12062634
TI  - Lymphocyte recruitment to the liver in alcoholic liver disease.
AB  - The normal liver contains a large number of lymphocytes, which include not only
      specialized natural killer (NK) and NKT cells but also CD4 and CD8 T cells.
      Whereas some of these cells are terminally differentiated effector cells that are
      destined to die by apoptosis, many of them are not and include immunocompetent
      cells that traffic through the liver to provide continuing immune surveillance as
      well as epithelial-associated effector T cells. In alcoholic liver disease the
      number of lymphocytes in the liver increases and the type and distribution of
      these infiltrating cells will determine the nature of the inflammation. For
      instance, a predominance of parenchymal inflammation is a feature of alcoholic
      hepatitis, whereas a predominantly portal infiltrate is a feature of cirrhosis.
      In this article we discuss the molecular mechanisms that regulate the entry of
      lymphocytes to the inflamed liver in alcoholic hepatitis. Lymphocytes play a
      critical role in regulating the immune/inflammatory response to alcohol, and
      understanding how these cells are recruited to the liver has important
      implications for understanding the pathogenesis of alcoholic liver disease in
      which parenchymal infiltration is a critical determinant of disease progression.
      Aberrant recruitment and retention of lymphocytes in the liver may explain why
      some patients with alcoholic liver disease show progressive inflammatory damage
      whereas in others the disease takes a more indolent course. Similarly, leukocyte
      recruitment may present new therapeutic targets in which lymphocyte recruitment
      to the specific liver compartments can be inhibited, thereby minimizing tissue
      damage whilst leaving generalized lymphocyte recirculation intact. Potentially
      the most exciting potential is to modulate the nature of the lymphocyte subsets
      recruited to the liver, so that harmful cells are excluded and beneficial subsets
      are preferentially recruited.

PMID- 12062635
TI  - Lymphocyte-mediated liver injury in alcohol-related hepatitis.
AB  - The pathogenesis of alcohol-related liver disease (ALD) remains inadequately
      explained. Increasing alcohol intake is associated with an increased risk of ALD,
      but many heavy drinkers develop no liver damage. An explanation for ALD
      susceptibility requires theories that extend beyond a biochemical understanding
      of alcohol metabolism. Several hepatic cell populations are involved in the
      pathogenesis of liver injury. The liver-associated lymphocyte (LAL) response to
      alcohol intake plus immune stimulation may determine susceptibility to liver
      damage. We have isolated rat LALs and demonstrated the following: (1) Liver
      associated lymphocytes differ from the peripheral blood lymphocyte pool; the
      CD8:CD4 ratio is higher in the LAL population than in peripheral blood. (2) Tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 production by these cells is
      suppressed by regular alcohol intake. (3) Tumor necrosis factor-alpha and
      interleukin-6 production by LALs is increased after parenteral administration of
      concanavalin A (Con A) and by Con A in in vitro LAL cultures obtained from
      healthy (control) and ethanol-consuming rats. (4) In vivo stimuli that lead to
      increased cytokine production by LALs lead, within 12-24 h, to increased
      hepatocyte necrosis [elevated alanine aminotransferase (ALT) levels] and
      apoptosis. (5) Liver-associated lymphocytes isolated from ethanol-consuming rats,
      transferred to non-ethanol-consuming rats, confer on the latter animals an
      ethanol-consuming response to Con A. (6) Cytokine release by LALs is
      quantitatively as significant as that from Kupffer cells after exposure to
      lipopolysaccharide. (7) In co-culture studies inhibition of TNF-alpha activity
      reduces hepatocyte apoptosis induced in the presence of activated LALs. (8)
      Finally, nuclear factor-kappa B inhibition decreases production of nitric oxide
      and TNF-alpha, with an associated reduction in hepatocyte apoptosis. In summary,
      our study findings support the suggestion that a role for LALs exists in the
      pathogenesis of alcohol and Con A-mediated liver disease.

PMID- 12062636
TI  - Alcoholic hepatitis: inflammatory cell-mediated hepatocellular injury.
AB  - The role that inflammatory cell injury plays in the pathogenesis of alcoholic
      liver disease is reviewed with emphasis on granulocytes and immunocytes. New
      insights regarding the mechanism of lymphocytic migration from the portal vein
      and lymphocytic-mediated hepatocellular injury are also reviewed.

PMID- 12062637
TI  - Role of activated CD8+ T cells in the initiation and continuation of hepatic
      damage.
AB  - The cause of alcoholic liver disease (ALD) is multifactorial and poorly
      understood. It is clear that alcohol alone is not responsible for most of the
      changes associated with ALD and that cofactors are involved in initiation and
      production of ALD. One cofactor that has received a great deal of attention
      recently is the concomitant infection with hepatitis C virus (HCV) and alcohol
      abuse. The interactive effects of HCV and alcohol abuse are still unclear, but
      apparently they are the result of an inability of the immune system to control
      the viral infection and exaggerated hepatocyte damage mediated by either the
      cells of the inflammatory response or factors produced by the inflammatory cells.
      This review will focus on one aspect of the possible pathogenic effects
      associated with alcohol abuse and HCV infection: the possible role of the immune
      system, notably the cytotoxic T lymphocyte (CTL) response. It is clear that the
      development of a CTL response is critical for the control of HCV infections, and
      it is also likely that this response is involved in liver damage. In this review,
      the evidence that shows the importance of the CD8(+) CTL in viral clearance and
      the role for pathogenesis will be presented. Findings obtained from animal
      studies that support the suggestion that activated CD8(+) CTLs can induce liver
      damage will be presented, as will results of recent studies from my laboratory
      that provide evidence for an effect of alcohol to enhance the liver damage
      mediated by activated CD8(+) T cells.

PMID- 12062638
TI  - Monocyte activation in alcoholic liver disease.
AB  - Activated monocytes and macrophages have been postulated to play an important
      role in the pathogenesis of alcoholic liver disease (ALD). Monocyte activation
      can be documented by measurement of neopterin, adhesion cell molecules, and
      certain proinflammatory cytokines and chemokines. We first became interested in
      the role of monocytes and monocyte-derived cytokines in ALD in relation to
      altered zinc metabolism that occurs regularly in ALD. Patients with ALD have
      hypozincemia, which responds poorly to oral zinc supplementation. We have shown
      that in ALD monocytes make a low-molecular-weight substance that, when injected
      into rabbits, causes prominent hypozincemia. Subsequently, multiple cytokines
      [especially tumor necrosis factor (TNF) and interleukin (IL)-8] have been shown
      to be overproduced by monocytes in ALD. We initially showed that monocytes in ALD
      spontaneously produce TNF and overproduce TNF in response to a lipopolysaccharide
      (LPS) stimulus, and this could be attenuated by antioxidants in vitro and in
      vivo. Alterations in the endotoxin-binding protein LPS-binding protein, in CD14,
      and in the endotoxin receptor Toll-like receptor 4 all may play roles in enhanced
      proinflammatory cytokine signaling in ALD. Moreover, several groups have
      documented increased TNF receptor density in monocytes in ALD. Inadequate
      negative regulation of TNF occurs at multiple levels in ALD. This includes
      decreased monocyte production of the important antiinflammatory cytokine IL-10
      and blunted response to the antiinflammatory properties of adenosine. Finally,
      generation of reactive oxygen species (which occurs during alcohol metabolism)
      and products of lipid peroxidation induce production of cytokines, such as TNF
      and IL-8. In conclusion, there are multiple overlapping potential mechanisms for
      enhanced proinflammatory cytokine production by monocytes in ALD. We postulate
      that activation of monocytes and macrophages with subsequent proinflammatory
      cytokine production plays an important role in certain metabolic complications of
      ALD and is a component of the liver injury of ALD.

PMID- 12062639
TI  - Ethanol, oxidative stress, and cytokine-induced liver cell injury.
AB  - Both clinical findings and results of experiments with animal models of alcoholic
      hepatitis have shown the importance of cytokine-mediated cell-cell interactions
      in the onset of ethanol-induced liver damage. Proinflammatory cytokines, such as
      tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta (IL-1 beta), and
      interleukin-6, are released from Kupffer cells or infiltrating neutrophils and
      macrophages and elicit defensive responses in parenchymal cells, including
      activation of apoptosis. Reactive oxygen species (ROS) and reactive nitrogen
      species (RNS), generated in response to cytokine-induced stress signals in
      parenchymal cells and also by activation of Kupffer cells and inflammatory cells,
      further mobilize cellular defense mechanisms. When these defensive responses are
      overwhelmed cells may die by necrosis, further stimulating inflammatory responses
      and infiltration of neutrophils. Chronic ethanol intake (i.e., many years of
      heavy alcohol use in human patients, several weeks or months in experimental
      animals) enhances the damaging consequences of these events through a variety of
      mechanisms. The formation of cytokines in the liver is stimulated by increasing
      circulating levels of endotoxin and by enhancing the responsiveness of Kupffer
      cells to such stimuli. In addition, ethanol promotes oxidative stress, both by
      increased formation of ROS and by depletion of oxidative defenses in the cell.
      Furthermore, liver cells from ethanol-treated animals are more susceptible to the
      cytotoxic effects of TNF-alpha and other cytokines than cells from control
      animals. Mitochondria play a critical role in the apoptotic response, and
      alterations in mitochondrial function after chronic ethanol treatment may
      contribute to enhanced cell death by apoptosis or necrosis. How the shift in the
      balance of cytokine-induced defensive and damage responses in hepatocytes
      contributes to the liver injury that occurs in alcoholic hepatitis remains poorly
      characterized and should be a rewarding area for future studies.

PMID- 12062640
TI  - Interaction of alcohol and hepatitis viral proteins: implication in synergistic
      effect of alcohol drinking and viral hepatitis on liver injury.
AB  - Alcohol drinking and viral hepatitis are both recognized as major causes of liver
      disease worldwide, and they frequently coexist and synergistically cause liver
      injury in patients with chronic liver disease. Several mechanisms have been
      implicated in exacerbation of liver injury in patients with alcohol drinking and
      viral hepatitis. These include impairment of host defense and liver regeneration
      by alcohol consumption. The findings obtained from my laboratory have
      demonstrated that alcohol potentiates cooperatively several signals activated by
      hepatitis B virus X protein (HBX) or hepatitis C virus core protein, and HBX
      sensitizes hepatocytes to tumor necrosis factor-alpha (TNF-alpha)- and ethanol
      induced apoptosis by a caspase-3-dependent mechanism, which may also contribute
      to the synergistic effect of alcohol drinking and viral hepatitis on liver
      injury.

PMID- 12062641
TI  - Concentration determination of methyl magnesium chloride and other Grignard
      reagents by potentiometric titration with in-line characterization of reaction
      species by FTIR spectroscopy.
AB  - A potentiometric titration method for methyl magnesium chloride and other
      Grignard reagents based on the reaction with 2-butanol in THF has been developed
      and validated. The method employs a commercially available platinum electrode,
      using an electrolyte compatible with non-aqueous solvents. Well-defined titration
      curves were obtained, along with excellent method precision. The endpoint was
      precisely determined based on the first derivative of the titration curve.
      Different solvents such as THF, diethyl ether and methylene chloride provided
      similar results with regard to sharpness of the endpoint and method precision.
      The method was applied to a wide array of Grignard reagents including methyl
      magnesium bromide, ethyl magnesium chloride, propyl magnesium chloride, vinyl
      magnesium chloride, phenyl magnesium chloride, and benzyl magnesium chloride with
      similar precision and accuracy. Application of in-line FTIR was demonstrated for
      in situ monitoring of the titration reaction, allowing characterization of the
      reaction species. An authentic spectrum of the MeMgCl-THF complex was obtained
      using spectral subtraction and the vibrational absorbance bands were identified.
      FTIR also provided an alternative for detecting the titration endpoint, and the
      titration results so obtained, provided a cross-validation of the accuracy of the
      potentiometric titration.

PMID- 12062642
TI  - Comparison of several methods used for the determination of cephalosporins.
      Analysis of cephalexin in pharmaceutical samples.
AB  - The precision of UV absorbance of intact and acid degraded cephalosporins,
      ninhydrin, high performance liquid chromatography and iodometric methods used for
      analysis of cefoxitin, cefotaxime, cephazolin and cephalexin were compared. To
      obtain the calibration graphs the analytical signal used were: absorbance, first
      derivative absorbance, second derivative absorbance and H-point Standard
      Additions Method by using absorbance values at two selected wavelengths as
      analytical signal. These methods and calibration graphs were also used for the
      determination of cephalexin in pharmaceutical samples.

PMID- 12062643
TI  - Chromatographic determination of the association constants between nimesulide and
      native and modified beta-cyclodextrins.
AB  - The retention of a non-steroidal anti-inflammatory drug (NSAID), i.e. nimesulide,
      in high performance liquid chromatography (HPLC) was investigated using a phenyl
      bond silica column and beta-cyclodextrin (beta-CD) or hydroxypropyl-beta
      cyclodextrin (HP-beta-CD) as mobile phase additive (0-10 mM). Such a study was
      carried out in order to determine the most efficient cyclodextrin as a potential
      drug complexing agent for a future application in pharmaceutical formulation.
      Assuming a 1:1 stoichiometry, the association constants (K) were calculated from
      the chromatographic data. At a column temperature of 25 degrees C and in a highly
      aqueous medium (98% phosphate buffer-2% methanol (v/v)), K was equal to 523 and
      1285 M(-1) for the nimesulide-beta-CD and nimesulide HP-beta-CD complexes,
      respectively. These results were consistent with the data reported previously
      using phase solubility studies and UV spectrophotometry. As well, the
      thermodynamic parameters of the inclusion complexes were determined from linear
      van't Hoff plots for the two inclusion complexes. From the enthalpy and entropy
      changes, it appeared that nimesulide interact more strongly with HP-beta-CD due
      to a significant hydrophobic effect between the compound and the flexible
      hydroxypropyl groups.

PMID- 12062644
TI  - Immunochemical characterisation of species-specific antigens in bovine crude
      heparin.
AB  - In order to develop immunoassays for the control of the species origin of crude
      heparins, polyclonal antisera were produced in rabbits against samples obtained
      from the last purification steps of bovine intestinal crude heparin. The
      reactivity of the antisera was analysed by agar gel double immunodiffusion,
      immunoelectrophoresis, crossed and line immunoelectrophoresis. Up to 13 antigenic
      components were detected in the effluents of the ion-exchange chromatographic
      step, and three in the final crude heparin. The major and most anodic antigen
      (Ag1) was recovered in bovine crude heparin purified by the two different
      industrial processes. This bovine specific antigen was found in high
      concentrations in lung, liver, small intestine, spleen and kidney. It displayed
      an apparent molecular weight of 45 kDa by size-exclusion chromatography. Though
      the identification of Ag1 is not yet fully elucidated, a single radial
      immunodiffusion assay has been developed for the quantification of this antigen,
      allowing the detection of 6 p 1000 bovine crude heparin in porcine heparin (50
      mg/ml) after 2 h diffusion.

PMID- 12062645
TI  - Characterisation of Ag1, the major species-specific contaminant of bovine crude
      heparin, and its identification as an aprotinin/heparin complex.
AB  - Heparin is a potent anticoagulant polysaccharide purified for decades from
      ruminants or porcine tissues. However, with the emergence of bovine spongiform
      encephalopathy (BSE), the source of pharmaceutical heparin is currently
      restricted to porcine intestinal mucosa. A major species-specific contaminant,
      called Ag1, has recently been identified in bovine crude heparin [Rivera et al.,
      J. Pharm. Biomed. Anal., submitted] and used to develop an enzyme-linked
      immunosorbent assay (ELISA) for the species origin control of crude heparins
      [Levieux et al., J. Immunoassay, submitted]. In this report, we describe the
      different investigations, which were carried out to identify Ag1. This antigen
      was first localised by immunohistological studies essentially in the connective
      tissue of the bovine small intestine. After extraction from an intestinal extract
      by immuno-affinity chromatography, Ag1 was isolated as a single band by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). Ag1 was then
      partly sequenced and identified as an aprotinin/heparin complex. Aprotinin, also
      known as the bovine pancreatic trypsin inhibitor (BPTI), is present with heparin
      in mast cells, and is very resistant to heat, pH, chemical treatments and
      proteolytic digestion. The stability of Ag1 towards the different treatments
      performed during heparin extraction process allows this protein to remain in
      sufficient amounts in crude heparin and makes it an ideal target for the
      immunochemical control of the absence of bovine material in crude heparins.

PMID- 12062646
TI  - FT-IR and Raman spectroscopic methods for identification and quantitation of
      orthorhombic and monoclinic paracetamol in powder mixes.
AB  - FT-IR and Raman spectroscopic methods are suggested for identification of
      orthorhombic (form II) and monoclinic (form I) paracetamol and for their
      quantitative determination in mixes. The intensity ratio of the 836 cm(-1) FT-IR
      band (attributed to the presence of both forms) to the 806 cm(-1) monoclinic band
      plotted against the inverse monoclinic molar fraction (X) yields a straight line:
      I(836)/I(806)=0.515/X+0.700, r=0.9965 for eight calibration points on the
      regression line. Similarly, the area under the 454 cm(-1) band in FT-Raman
      spectra (which is attributed to both forms) over the area under the 465 cm(-1)
      band of monoclinic form is inversely related to its molar fraction (X):
      A(454)/A(465)=0.482/X-0.324, r=0.9954 for eight calibration points. Precision
      (RSD%) was <5% for both methods. Linear regression analysis between content and
      intensity of characteristic XRD reflections for four different samples gave
      r=0.9964 at 4.62 A and r=0.9894 at 3.70 A, for form II. For the content of form
      I, r=0.9596 at 3.37 A. The limit of detection for monoclinic form was estimated
      to be 0.012 mole fraction for both methods.

PMID- 12062647
TI  - Multiple fiber-optic dual-beam UV/Vis system with application to dissolution
      testing.
AB  - A system for fiber-optic probing in dissolution testing of solid pharmaceutical
      formulations has been constructed. The system is based on an imaging spectrometer
      and a charged coupled device (CCD) detector and includes 12 fiber-optic probes
      with a novel dual-path design. UV light was produced by a small arc deuterium
      lamp illuminating an optical fiber bundle. Twelve fiber-optic dipping probes were
      constructed with a reflection geometry. A 5 mm diameter lens was used to achieve
      a parallel light beam. The light passed back and forth through the flow-through
      cuvette defined by a sapphire window and a coated aluminium mirror. The mirror
      was cut in half and each segment was tilted and set at different distances from
      the window to obtain two separate paths with different lengths. Two receiver
      fibers were used for each probe to collect the transmitted light. The 24 receiver
      fibers from the 12 probes were bunched to a linear bundle and fed to an imaging
      spectrometer and the corresponding spectra were detected with a 512 x 512 pixel
      cooled CCD detector. The sampling interval was typically a few seconds for all
      probes. A software package was developed for data recording and on-line analysis.
      The program includes tools for multi-component analysis. The system was tested
      for different tablet formulations. Prednisone 50 mg tablets, normally used for
      control tests of dissolution baths, were followed for 3 h. Secondly, an extended
      release low dosage tablet was followed for 7 h resulting in a linear dissolution
      profile. Finally, a combination tablet containing two active drugs was tested for
      60 min profiles. In the latter case, separate dissolution curves for the two
      active components were obtained. Future work will mainly focus on further
      development of the multi-component capability of the system.

PMID- 12062648
TI  - Resolution of ternary mixtures of nitrofurantoin, furaltadone and furazolidone by
      partial least-square analysis to the spectrophotometric signals after photo
      decomposition.
AB  - An UV spectroscopic method is proposed to analyze mixtures of the nitrofuran
      derivatives, nitrofurantoin, furaltadone and furazolidone, used in veterinary.
      The change of absorption spectra due to photo-decomposition is used. A 20%
      dimethylformamide/water, basic medium of pH 9.4 (ammonium chloride/ammonia) and a
      time of irradiation of 15 s are selected. Calibration graphs are established,
      with the percentage of decrease of absorbance as analytical signal, in the range
      2-10 microg ml(-1). To analyze mixtures of the three compounds the partial least
      squares (PLS) multivariate analysis method is used with the spectra obtained by
      subtracting the spectra after irradiation to the original spectra. Good results
      have been obtained in the analysis of synthetic samples and a formulation
      containing all these compounds.

PMID- 12062649
TI  - Kinetic degradation study of insulin complexed with methyl-beta cyclodextrin.
      Confirmation of complexation with electrospray mass spectrometry and (1)H NMR.
AB  - Hydrolysis of insulin has been studied during storage of various preparations at
      different temperatures. Deamidation is the predominant degradation process in
      acid solution resulting in a desamido product. The current study examines whether
      the interaction of insulin with methyl-beta cyclodextrin (met beta CD) improves
      its stability. Hydrolysis of insulin was monitored by an HPLC assay with
      ultraviolet detection. The stability constant of insulin-met beta CD complex was
      calculated by Lineweaver-Burke linear equation. Furthermore, the complexation of
      insulin with met beta CD was characterized by (1)H NMR and Electrospray Mass
      Spectrometry (ESI-MS). Met beta CD had a stabilizing effect on insulin
      degradation according to the kinetic parameters, leading to a decreased chemical
      deterioration. Furthermore, the stability constant K(st) and the activation
      energy E(a) were calculated by fitting the kinetic results to Lineweaver-Burke
      and to Arrhenius linear equations, respectively. Finally, the complexation of
      insulin with met beta CD was characterized in aqueous media by (1)H NMR chemical
      shift displacements of assignable aromatic protons of specific amino acids upon
      the addition of the cyclodextrin, as well as by ESI-MS, since additional m/z
      peaks, which were attributed to insulin-met beta CD complex, were detected. It is
      concluded that addition of met beta CD resulted in a significant increase in the
      stability of complexed insulin compared with free insulin.

PMID- 12062650
TI  - NMR and Bayesian regularized neural network regression for impurity determination
      of 4-aminophenol.
AB  - A method for the determination of 4-aminophenol as an impurity in paracetamol (N
      (4-hydroxyphenyl)-acetamide) by proton nuclear magnetic resonance ((1)H-NMR)
      spectroscopy has been developed. The (13)C-satellite from the protons in the
      ortho position from the hydroxyl group in paracetamol was used as an internal
      standard, although these peaks interfered with the peaks from the protons in 4
      aminophenol. Because of interference in the spectra and non-linearity over a wide
      calibration range, a Bayesian regularized neural network model was used for
      calibration. Various kinds of data preprocessing were examined: zero filling,
      multiplication by a negative exponential function (line broadening), followed by
      Fourier transformation of the free induction decay (FID). The NMR spectral data
      were automatically phased and shift-adjusted by means of a genetic algorithm.
      Multiplicative scatter correction and data compression by wavelets and sequential
      zeroing of weights variable selection were performed to obtain an optimal
      calibration model. Neither zero filling of the FID nor line broadening improved
      the calibration models with regard to error of prediction, so these processes
      were excluded in the final model. The generated Bayesian regularized network
      model was evaluated with an independent test set. Four different models with
      different test sets were constructed to explore the quality of the calibration.
      The mean error of the optimal calibration model was 25.3 x 10(-6) weight of 4
      aminophenol per weight paracetamol. The method is characterized by being relative
      fast, simple and sufficient sensitive for typical pharmaceutical impurity
      determinations.

PMID- 12062651
TI  - High-speed gas chromatographic analysis of solvents in pharmaceuticals using
      solid phase microextraction.
AB  - A simple, inexpensive and rapid analytical approach for the determination of
      organic volatile impurities in pharmaceutical drug substances is developed, where
      sample preparation step was conducted using solid phase microextraction (SPME),
      followed by a fast GC separation. With an extraction time between 3 and 5 min and
      separation of 13 solvents in less than 3 min employing fast temperature
      programming using resistively heated column, organic volatile impurities can be
      analyzed within a total analysis time of 6-9 min. Various SPME phases were
      evaluated towards sensitivity and selectivity for the extraction of 13 commonly
      found solvents in drug substances dissolved in dimethyl sulfoxide and water. A 2
      cm Carboxen/polydimethyl siloxane/divinylbenzene (Carboxen/PDMS/DVB) phase and a
      65-microm DVB/PDMS phase showed better sensitivity towards these solvents when
      extracted from organic and aqueous matrix in comparison with the sensitivity
      obtained with direct injection approach. Extraction parameters such as extraction
      time, extraction stir rate, etc. are discussed. %RSD of peak area of replicate
      extraction was between 2 and 10% when 100 microm PDMS was used for extracting
      solvents from aqueous matrix. When DVB/PDMS fiber was evaluated for precision,
      %RSD of peak area from replicate extractions of solvents from organic matrix was
      between 2 and 8%. One-hundred micrometer PDMS showed excellent linearity from 10
      to 500 microg/ml for analytes extracted from water solutions. On the other hand,
      DVB/PDMS phase showed better linearity than Carboxen/PDMS/DVB fiber when it was
      used to extract analytes in the concentration range of 10-5000 microg/ml from
      organic matrix.

PMID- 12062652
TI  - Simultaneous LC determination of some antidepressants combined with neuroleptics.
AB  - A reversed-phase HPLC method with UV detection at 252 nm is presented for the
      simultaneous determination of some tricyclic antidepressants (amitriptyline,
      imipramine) and neuroleptics (chlorprothixene, thioridazine) in their quaternary
      mixtures. Sample analysis was performed on a bonded reversed phase C-18, 5
      microm, 250 x 4.6 mm ID (Lichrospher 100RP-18) column using acetonitrile and 0.01
      M aqueous solution of triethylamine (1:1) as the mobile phase at 0.9 ml/min. The
      pH was adjusted to 2.7 with concentrated phosphoric acid. The retention time was
      for imipramine, amitriptyline, chlorprothixene, and thioridazine 5.8, 6.5, 8.3,
      10.8 min, respectively. The linearity was obeyed up to 15 ppm for imipramine and
      amitriptyline, 12 ppm for chlorprothixene and 10 ppm for thioridazine. The
      presented method also allows the determination of the mentioned drugs
      individually in their pharmaceutical preparations.

PMID- 12062653
TI  - Spectrophotometric determination of beta-adrenergic blocking agents in
      pharmaceutical formulations.
AB  - Simple, rapid and sensitive spectrophotometric procedures were developed for the
      analysis of atenolol, timolol maleate, propranolol hydrochloride, metoprolol
      tartarate, betaxolol hydrochloride, levobunolol hydrochloride and bisprolol
      fumarate in pure form as well as in their pharmaceutical formulations. The
      methods are based on the reaction of these drugs as n-electron donors with the
      sigma-acceptor iodine, and the pi-acceptors: 7,7,8,8-tetracyanoquinodimethane,
      2,3-dichloro-5,6-dicyano-1,4-benzoquinone, tetracyanoethylene, 2,3,5,6-tetrabromo
      1,4-benzoquinone (bromanil) and 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil).
      The obtained charge-transfer complexes were measured at 365 nm for iodine (in 1,2
      dichloroethane), at 840, 420, and 470 nm for 7,7,8,8-tetracyan-oquinodimethane,
      tetracyanoethylene and 2,3-di-chloro-5,6-dicyano-1,4-benzoquinone (in
      acetonitrile), respectively, and at 450 and 440 nm for bromanil and chloranil (in
      ethanol), respectively. Due to the rapid development of colors at ambient
      temperature, the obtained results were used on thin-layer chromatograms for the
      detection of the investigated drugs. Beer's plots were obeyed in a general
      concentration range of 4-120 microg ml(-1) with correlation coefficients not less
      than 0.9991. The proposed procedures could be applied successfully to the
      determination of the investigated drugs in tablets and ophthalmic solutions with
      good recovery; percent ranged from 98.03+/-0.98 to 100.30+/-0.90. The association
      constants and standard free energy changes using Benesi-Hildebrand plots were
      studied.

PMID- 12062654
TI  - HPTLC determination of diclofenac sodium from serum.
AB  - Diclofenac sodium is one of the potent Non Steroidal Anti-Inflammatory Drugs
      (NSAID) used in the treatment of inflammatory conditions. The present work deals
      with the estimation of diclofenac sodium from serum by a novel High Performance
      Thin Layer Chromatographic (HPTLC) method developed in our laboratory. Standard
      diclofenac sodium was spotted on Silica Gel 60 F(254) precoated plates, which
      were developed using the mobile phase toluene:acetone:glacial acetic acid
      (80:30:1,v/v/v). Densitometric analysis of diclofenac sodium was carried out at
      280 nm with diclofenac being detected at an R(f) of 0.58. The method was
      subsequently developed to estimate diclofenac sodium from serum. Diclofenac
      sodium was extracted with ethyl acetate from serum samples, spotted on Silica Gel
      60 F(254) plates and the plates were developed using the above mentioned mobile
      phase. The method was validated for selectivity, extraction efficiency,
      sensitivity, accuracy, and intra and inter-day reproducibility studies. The
      extraction efficiency was found to range from 76 to 80%. The Limit of Detection
      (LOD) and Limit of Quantification (LOQ) of diclofenac sodium in serum were found
      to be 90 and 120 ng, respectively. The calibration curve of diclofenac sodium in
      serum was found to be linear in the range of 200-800 ng. The mean values (+/
      S.D.) of correlation coefficient, slope and intercept were found to be 0.9876 (+/
      0.0105), 0.0228 (+/-0.0036) and 6.15 (+/-1.4), respectively. The mean percentage
      coefficient of variation for accuracy, intra-day and inter-day analysis at 200
      800 ng of diclofenac sodium were found to be 3.2, 6.35 and 8.025, respectively.
      The proposed method is a simple and sensitive method with good precision and
      reproducibility for the estimation of diclofenac sodium form serum samples.

PMID- 12062656
TI  - Characterization of interaction between protein and carbohydrate using CZE.
AB  - The present study describes the application of the capillary zone electrophoresis
      (CZE) to investigate interactions between Concanavalin A (Con A) and the one of
      their major components (L-asparagin) with a variety of carbohydrates (D-glucose,
      D-fructose, D-mannose D-galactose, maltose and lactose). It was observed that the
      carbohydrates show different interactions with Con A and L-asparagin. Addition of
      carbohydrates to the electrolyte buffer and different concentrations of
      carbohydrates led to a change of the migration time and the ionic mobility of Con
      A and L-asparagin. A mathematical model for quantitative evaluation to calculate
      the aggregation constants (K) was used. Our investigations show that it is
      possible to characterize the interaction between carbohydrates and proteins or
      amino acid quantitatively using CZE.

PMID- 12062655
TI  - Spectrophotometric determination of enoxacin as ion-pairs with bromophenol blue
      and bromocresol purple in bulk and pharmaceutical dosage form.
AB  - Three simple, accurate and sensitive spectrophotometric methods were developed
      for determination of enoxacin. The methods based on extraction of this drug into
      chloroform as ion pairs with sulphonphthalein dyes as bromophenol blue and
      bromocresol purple. The optimum conditions of the reactions were studied and
      optimized. The absorbance of yellow products was measured at 412 nm for enoxacin
      bromophenol blue and 410 nm for enoxacin-bromocresol purple. Linearity ranges
      were found to be 2.0-20.0 microg ml(-1) for enoxacin-bromophenol blue and 0.77
      17.62 microg ml(-1) for enoxacin-bromocresol purple. The detection limits were
      found to be 0.084 microg ml(-1) and 0.193 microg ml(-1) for enoxacin-bromophenol
      blue and enoxacin-bromocresol purple, respectively. The composition of the ion
      pairs was found 1:1 by Job's method. The developed methods were applied
      successfully for the determination of this drug in pharmaceutical preparation.
      The data obtained by developed methods were compared with the spectrophotometric
      method in literature. No differences were found statistically.

PMID- 12062657
TI  - Voltammetric behavior of benznidazole at a DNA-electrochemical biosensor.
AB  - Benznidazole is a drug used commonly as a therapeutic agent against Chagas'
      disease in Brazil. To clarify the cytotoxic action of benznidazole the
      electrochemical reduction of benznidazole has been investigated using a DNA
      electrochemical biosensor, prepared by modification of a glassy carbon electrode
      with DNA, and the results compared with reduction at a bare glassy carbon
      electrode. The dependence of peak potential with pH follows slopes of 59 and 52
      mV per pH unit in acid media, respectively, which corresponds to a mechanism
      involving the same number of electrons and protons. In neutral and alkaline
      solution no significant dependence of peak potential with pH was found. During
      the electrochemical reduction of benznidazole the formation of the hydroxylamine
      derivative occurs, involving a total of four electrons. The potentials for
      reduction were less negative when using the DNA-modified glassy carbon electrode
      than at the bare glassy carbon electrode although the mechanism was the same, and
      at pH 7.51 the peak current was four times higher than that obtained with the
      bare electrode. The DNA-biosensor enabled pre-concentration of the drug onto the
      electrode surface and the in situ damage caused to the DNA on the electrode
      surface by the product of benznidazole reduction could be detected
      electrochemically. The results are in agreement with the hypothesis that the
      hydroxylamine derivative is the reactive species responsible for the cytotoxic
      action of benznidazole.

PMID- 12062658
TI  - Monitoring of enzymatic hydrolysis of penicillin G by pyrolysis-negative ion mass
      spectrometry.
AB  - A pyrolysis-negative ion mass spectrometry (Pyr-NIMS) is used for the monitoring
      of enzymatic hydrolysis of penicillin G (Pen G) to 6-aminopenicillanic acid (6
      APA) and phenyl acetic acid (PAA). The high sensitivity and rapid response time
      of Pyr-NIMS allow its application to the simultaneously determination of these
      compounds. The mass to charge (m/z) values of 262, 156 and 135 of Pen G, 6-APA
      and PAA respectively, are used for the quantitative measurements by selected ion
      monitoring (SIM). The limit of detection (LOD), linearity and relative standard
      deviation (n=5) are 10 ng ml(-1), 100 ng ml(-1)-1000 mg ml(-1) and 1.5%,
      respectively The results are compared with high performance liquid chromatography
      (HPLC). An important advantage of the presented analytical system is the high
      linearity of signals without preliminary separation and recalibration. The main
      and interactive effects of pH, temperature and concentration of Pen G for
      enzymatic hydrolysis of Pen G are studied. Optimize conditions of pH (8),
      temperature (28 degrees C) and concentration of Pen G (12% w/v) in real samples
      are obtained.

PMID- 12062659
TI  - Spectrofluorimetric and spectrophotometric methods for the determination of
      vigabatrin in tablets.
AB  - Two sensitive and selective spectrofluorimetric and spectrophotometric methods
      have been developed for the determination of vigabatrin in tablets. The methods
      are based on derivatization with 7-chloro-4-nitrobenzofurazan (NBD-Cl). The
      product showed an absorption maximum at 460 nm and a fluorescence emission peak
      at 520 nm in ethyl acetate. The color was found to be stable for at least 48 h in
      this solvent. The optimum conditions of the reaction were investigated and it was
      found that the reaction proceeds quantitatively at pH 10.0, 70 degrees C in 50
      min when the mole ratio of the reagent to drug was 30. The reaction obeys Beer's
      law over the ranges of 2-10 and 0.05-1.00 microg ml(-1) for the
      spectrophotometric and spectrofluorimetric measurements, respectively. The
      detection limits were found to be 0.50 and 0.01 microg ml(-1) for the
      spectrophotometric and spectrofluorimetric methods, respectively. The proposed
      methods were applied to the assay of vigabatrin in tablets. The results were
      compared statistically with those obtained by the modified spectrofluorimetric
      method reported in the literature.

PMID- 12062660
TI  - Chemical reactivity of the naproxen acyl glucuronide and the naproxen coenzyme A
      thioester towards bionucleophiles.
AB  - Drugs may be metabolised to reactive electrophilic species that spontaneously
      react with proteins. The presence of such drug-protein adducts has been
      associated with drug toxicity. In this study, the reactivity of the major
      metabolite of naproxen--the 1-beta-O-glucuronide (Nap-GlcU)--was compared to the
      corresponding naproxen coenzyme A (Nap-CoA) thioester. The reactivity of the two
      metabolites was assessed in vitro in a phosphate buffer (pH 7.4; 0.1 M) at 37
      degrees C towards the model bionucleophiles glutathione and human serum albumin
      (HSA). The reaction between the electrophilic species (Nap-GlcU and Nap-CoA) and
      glutathione forming the Nap-glutathione conjugate was monitored using LC-MS-MS
      and LC-UV, respectively. It was shown that Nap-CoA resulted in an approximate 100
      fold higher formation of Nap-glutathione conjugate than Nap-GlcU. The presence of
      Nap-CoA also resulted in acylated HSA with a rate and a yield that was
      significantly higher than reported for Nap-GlcU. In summary, the data suggest
      that CoA metabolites may be more reactive species than acyl glucuronides that
      previously have been associated with severe drug related side effects in vivo.

PMID- 12062661
TI  - Determination of meropenem in plasma and filtrate-dialysate from patients under
      continuous veno-venous haemodiafiltration by SPE-LC.
AB  - Meropenem, a carbapenem antibiotic displaying a broad spectrum of antibacterial
      activity, is administered in Medical Intensive Care Unit to critically ill
      patients undergoing continuous veno-venous haemodiafiltration (CVVHDF). However,
      there are limited data available to substantial rational dosing decisions in this
      condition. In an attempt to refine our knowledge and propose a rationally
      designed dosage regimen, we have developed a HPLC method to determine meropenem
      after solid-phase extraction (SPE) of plasma and dialysate fluids obtained from
      patients under CVVHDF. The assay comprises the simultaneous measurement of
      meropenem's open-ring metabolite UK-1a, whose fate has never been studied in
      CVVHDF patients. The clean-up procedure involved a SPE on C18 cartridge. Matrix
      components were eliminated with phosphate buffer pH 7.4 followed by 15:85 MeOH
      phosphate buffer pH 7.4. Meropenem and UK-1a were subsequently desorbed with
      MeOH. The eluates were evaporated under nitrogen at room temperature (RT) and
      reconstituted in phosphate buffer pH 7.4. Separation was performed at RT on a
      Nucleosil 100-5 microm C18 AB cartridge column (125 x 4 mm I.D.) equipped with a
      guard column (8 x 4 mm I.D.) with UV-DAD detection set at 208 nm. The mobile
      phase was 1 ml min(-1), using a step-wise gradient elution program: %MeOH/0.005 M
      tetrabutylammonium chloride pH 7.4; 10/90-50/50 in 27 min. Over the range of 5
      100 microg ml(-1), the regression coefficient of the calibration curves (plasma
      and dialysate) were >0.998. The absolute extraction recoveries of meropenem and
      UK-1a in plasma and filtrate-dialysate were stable and ranged from 88-93 to 72
      77% for meropenem, and from 95-104 to 75-82% for UK-1a. In plasma and filtrate
      dialysate, respectively, the mean intra-assay precision was 4.1 and 2.6% for
      meropenem and 4.2 and 3.7% for UK-1a. The inter-assay variability was 2.8 and
      3.6% for meropenem and 2.3 and 2.8% for UK-1a. The accuracy was satisfactory for
      both meropenem and UK-1a with deviation never exceeding 9.0% of the nominal
      concentrations. The stability of meropenem, studied in biological samples left at
      RT and at +4 degrees C, was satisfactory with < 5% degradation after 1.5 h in
      blood but reached 22% in filtrate-dialysate samples stored at RT for 8 h,
      precluding accurate measurements of meropenem excreted unchanged in the filtrate
      dialysate left at RT during the CVVHDF procedure. The method reported here
      enables accurate measurements of meropenem in critically ill patients under
      CVVHDF, making dosage individualisation possible in such patients. The levels of
      the metabolite UK-1a encountered in this population of patients were higher than
      those observed in healthy volunteers but was similar to those observed in
      patients with renal impairment under hemodialysis.

PMID- 12062662
TI  - LC determination of loratadine and related impurities.
AB  - Loratadine, an antihistamine, could include in its raw material seven impurities
      that ought to be separated identified and quantified for drug development and
      quality control. A HPLC method employing a SymmetryShield RP8 column has been
      developed and validated for loratadine and related compounds measurement, the
      last ones under the 0.1% level. The mobile phase consisted of methanol-buffer A
      (65:35, v/v), being buffer A: H(3)PO(4) 10 mM (H(2)O) brought up to pH 7.00 with
      triethylamine. UV detection was performed at 244 nm. Validation parameters for
      linearity, accuracy and precision are in agreement with ICH guidelines for all
      the analytes and that permits to consider the method reliable and suitable for
      application to long-term stability and purity studies.

PMID- 12062663
TI  - Voltammetric determination of cilazapril in pharmaceutical formulations.
AB  - A sensitive adsorptive stripping voltammetric method for the measurement of
      cilazapril in 0.04 M Britton-Robinson buffer (pH 9.0) solution was described. The
      method was based on the adsorptive accumulation of the drug at a hanging mercury
      drop electrode (HMDE), followed by differential pulse voltammetry. The response
      was evaluated with respect to pre-concentration time, pH effect, accumulation
      potential, accumulation time and scan rate. The peak potential was -0.60 V (vs.
      Ag/AgCl). The peak current was directly proportional to the concentration of
      cilazapril with a detection limit of 17.6 ng ml(-1) at an accumulation time of 10
      s. The reduction process was irreversible and the wave showed adsorptive
      characteristics. The results were compared to those obtained using a HPLC
      procedure. A reversed-phase C18e column with aqueous phosphate buffer (pH 3.5;
      0.125 M)-acetonitrile (67:33, v/v) mobile phase and benazapril as internal
      standard was used. UV detector was set at 254 nm. Results obtained in HPLC were
      comparable to those obtained by adsorptive stripping voltammetric method.

PMID- 12062664
TI  - Second derivative spectrophotometric determination of trimethoprime and
      sulfamethoxazole in the presence of hydroxypropyl-beta-cyclodextrin (HP-beta-CD).
AB  - An easy and rapid second-derivative spectrophotometric method for the
      simultaneous analysis of trimethoprime (TMP) and sulfamethoxazole (SM) is
      described. These drugs have been used as antibacterial against a wide spectrum of
      organisms and combinations of these drugs are commonly used for the treatment of
      a variety of infections. The most advantageous approach of this method is the use
      of HP-beta-CD, which allows to improve the performance of the second-derivative
      ultraviolet spectrophotometry. For both compounds, a shift of the absorption
      bands and variations of their intensity were observed. The calibration graphs
      were linear in the concentration range of TMP (1.92-19.2 microg ml(-1)) and SM
      (1.60-16.5 microg ml(-1)), the correlation coefficient for the calibration graphs
      was better than 0.9994 and the precision was satisfactory (CV%< 4.96) in HP-beta
      CD solutions. The proposed method was successfully applied to the assay of
      commercial tablets. The results were compared to those obtained by second
      derivative ultraviolet spectrophotometry in the absence of HP-beta-CD. Thereby,
      the details of the statistical treatment of the analytical data are also
      presented.

PMID- 12062665
TI  - Improvements of conductivity measurements of electrolyte solutions using a new
      conductometric cell design.
AB  - A new conductometric cell design, for precise conductance measurements, has been
      developed and tested using aqueous lidocaine hydrochloride as a model system. A
      small portion of a stock solution in the conductivity cell is diluted stepwise by
      pure solvent. The resistance of the cell is measured by means of a precision
      conductance bridge. Contrary to conventional technique in precision
      conductometry, the temperature is allowed to change during the measurements and
      corrected to the desired standard temperature. The temperature is determined
      using a thermistor immersed in the cell solution, which is agitated during the
      entire experiment. Using this new approach, significant improvements over
      conventional conductivity technique were observed. The time required for the
      measurements was considerably reduced, by a factor of at least ten. The amounts,
      especially of costly drugs, required in the measurements are also reduced. The
      pK(a) value obtained, 7.28, is close to the previously reported
      conductometrically determined average, 7.18. The precision of the single
      conductivity value is equally high, if not higher, as that obtained using
      conventional conductivity technique.

PMID- 12062666
TI  - A HPLC assay for coating integrity of topiramate sprinkle formulation.
AB  - A HPLC method has been developed for the determination of coating integrity of
      topiramate sprinkle formulation. This method determines the completeness of the
      sprinkle coating and, indirectly, the completeness of taste masking of the
      product. This method utilizes a sample preparation where the sprinkles are placed
      in a specially designed stainless steel basket equipped with a screen, 25-mesh
      size, at the bottom. Water is used to solubilize any incompletely coated drug.
      The aqueous solution is analyzed for topiramate using a phenyl column in the
      reversed-phase mode, isocratic elution, and refractive index detection. This
      analytical method, for recovered topiramate, provides an indirect measure of drug
      taste-masking in the sprinkle formulation. It was also used in formulation
      selection by screening sprinkles beads that contained different amounts of
      coating to see which formula can best mask the taste with an acceptable level of
      exposed topiramate drug substance. This method has been validated to meet FDA
      validation guidelines.

PMID- 12062667
TI  - CE versus LC for simultaneous determination of amoxicillin/clavulanic acid and
      ampicillin/sulbactam in pharmaceutical formulations for injections.
AB  - A rapid, capillary electrophoresis method was evaluated for determination of
      amoxicillin and clavulanic acid in Augmentin as well as ampicillin and sulbactam
      in Unasyn preparations for injections. Phosphate-borate buffer at pH 8.66
      containing 14.4% sodium dodecyl sulfate was used as a mobile phase. The method
      was validated. Reproducibility, precision, accuracy and assay linearity in
      concentration of amoxicillin 0.05-3.03 mg/ml and ampicillin 0.05-3.08 mg/ml, as
      well as clavulanic acid 0.02-2.02 mg/ml and sulbactam 0.05-2.08 mg/ml were
      established. This new method is fast, inexpensive and limits consumption of
      organic solvents when compared with alternative high performance liquid
      chromatography (HPLC) method, used for drug analysis. Statistical analysis by
      Student's t-test showed no significant differences between the results obtained
      by the two methods t(calculated) 0.32 and 1.69 for amoxicillin and clavulanic
      acid and 0.67 and 1.93 for ampicillin and sulbactam were smaller than
      t(tabulated).

PMID- 12062668
TI  - Development and validation of a liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) method for the determination of ribavirin in human plasma and serum.
AB  - A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed
      for the analysis of antiviral agent ribavirin in human plasma and serum. The
      samples (0.1 ml) were extracted from the matrix using a simple protein
      precipitation procedure. The supernatants were evaporated to dryness,
      reconstituted and injected onto the LC/MS/MS system. The chromatography
      separation was achieved on a silica column operated with an aqueous-organic
      mobile phase. The use of a silica column not only provided adequate retention for
      the extremely polar compound of ribavirin, but also enhanced electrospray
      ionization sensitivity with the use of high percentage organic solvent in the
      mobile phase. The method has been validated over the concentration range of 10
      10000 ng/ml ribavirin in human plasma and serum. Bamethan was used as the
      internal standard. The protein precipitation extraction has been automated based
      on 96-well format with the use of robotic liquid handlers to improve the overall
      throughput of the analysis.

PMID- 12062669
TI  - Determination of laser-induced thymine-thymine dimer in DNA by LC.
AB  - A new simple and selective high-performance liquid chromatography (HPLC) method
      has been developed for the determination of thymine-thymine (T-T) dimer in
      deoxyribonucleic acid (DNA) for the study of relationship between the yield of T
      T dimer and laser irradiation conditions. The HPLC method is not disturbed by
      other hydrolysate formed in DNA with the good stability and reproducility. The
      detection of limit of the method is about 8.8 ng of T-T dimer in DNA blank. Three
      lever of laser intensity to irradiate DNA were selected for calf thymine to test
      the influence of the pulse number. The mechanism of DNA lesion and repair caused
      by laser irradiating was studied.

PMID- 12062670
TI  - Molecular descriptors that influence the amount of drugs transfer into human
      breast milk.
AB  - Most drugs are excreted into breast milk to some extent and are bioavailable to
      the infant. The ability to predict the approximate amount of drug that might be
      present in milk from the drug structure would be very useful in the clinical
      setting. The aim of this research was to simplify and upgrade the previously
      developed model for prediction of the milk to plasma (M/P) concentration ratio,
      given only the molecular structure of the drug. The set of 123 drug compounds,
      with experimentally derived M/P values taken from the literature, was used to
      develop, test and validate a predictive model. Each compound was encoded with 71
      calculated molecular structure descriptors, including constitutional descriptors,
      topological descriptors, molecular connectivity, geometrical descriptors, quantum
      chemical descriptors, physicochemical descriptors and liquid properties. Genetic
      algorithm was used to select a subset of the descriptors that best describe the
      drug transfer into breast milk and artificial neural network (ANN) to correlate
      selected descriptors with the M/P ratio and develop a QSAR. The averaged
      literature M/P values were used as the ANN's output and calculated molecular
      descriptors as the inputs. A nine-descriptor nonlinear computational neural
      network model has been developed for the estimation of M/P ratio values for a
      data set of 123 drugs. The model included the percent of oxygen, parachor,
      density, highest occupied molecular orbital energy (HOMO), topological indices
      (chiV2, chi2 and chi1) and shape indices (kappa3, kappa2), as the inputs had four
      hidden neurons and one output neuron. The QSPR that was developed indicates that
      molecular size (parachor, density) shape (topological shape indices, molecular
      connectivity indices) and electronic properties (HOMO) are the most important for
      drug transfer into breast milk. Unlike previously reported models, the QSPR model
      described here does not require experimentally derived parameters and could
      potentially provide a useful prediction of M/P ratio of new drugs only from a
      sketch of their structure and this approach might also be useful for drug
      information service. Regardless of the model or method used to estimate drug
      transfer into breast milk, these predictions should only be used to assist in the
      evaluation of risk, in conjunction with assessment of the infant's response.

PMID- 12062671
TI  - Stability indicating methods for assay of mequitazine in presence of its
      degradate.
AB  - Six procedures have been suggested for the determination of the antihistaminic
      agent, mequitazine, in the presence of its degradate. Mequitazine, having a
      phenothiazine group, undergoes peroxide oxidation and the corresponding sulphone
      is produced. Its identity was confirmed by IR and MS. The first procedure is
      based on determination of mequitazine by HPLC with UV detection at 256 nm. The
      mobile phase used is acetonitrile, ortho phosphoric acid (50:50) using caffeine
      as an internal standard. Linearity range is 1.00-9.00 microg/ml. The second
      determination is a densitometric procedure based on the determination of
      mequitazine in the presence of its degradate at 256 nm using the mobile phase,
      chloroform:methanol:ammonia (50:18:3). Linearity range is 1.25-7.50 microg per
      spot. The third procedure is spectrophotometric, where a mixture of mequitazine
      and its degradate are resolved by first derivative ratio spectra. Linear
      calibration graphs of first derivative values at wavelengths 210.2, 247 and 259.8
      nm are obtained. On carrying out measurements at the three mentioned wavelengths,
      the linearity range is found to be 1.00-10.00 microg/ml. The fourth procedure is
      based on first derivative spectrophotometry, where D(1) measurements are carried
      out at 290 nm. Linearity range is 1.00-10.00 microg/ml. The fifth procedure is
      based on the reaction of mequitazine with 3-methyl-2-benzothiazolinone hydrazone
      (MBTH) in the presence of ferric chloride. A stable violet colored oxidative
      coupling product is formed, which is measured spectrophotometrically at 685 nm.
      The optimum experimental parameters for the reaction have been studied and
      assigned. Linearity range is 1.00-16.00 microg/ml. The sixth procedure is based
      on the reaction of mequitazine in the presence of its degradate with 2,6
      dichloroquinone-4-chloroimide (Gibbs reagent) in aqueous methanolic medium. The
      reddish-brown colored condensation product is measured at 405 nm. The optimum
      experimental conditions for the reaction have been studied. Linearity range is
      50.00-600.00 microg/ml. The validity of the described procedures was assessed by
      applying the standard addition technique. Statistical analysis of the results has
      been carried out revealing high accuracy and good precision. The suggested
      procedures could be used for the determination of mequitazine, both in pure and
      dosage forms, as well as in the presence of its degradate.

PMID- 12062672
TI  - An automated LC method for the small-scale purification of organic molecules
      derived from combinatorial libraries.
AB  - This paper presented the development of an automated HPLC small-scale
      purification method for single bead compounds derived from combinatorial
      libraries. The method was found to produce higher and more consistent recoveries
      of purified compounds as compared to conventional manual HPLC purification. Using
      the manual method, the average percentage recovery of one synthetic compound was
      determined to be 24% and the coefficients of variation (C.V.%) of recovery were
      found to be greater than 38%. Using the automated system, the average percentages
      recovery of a standard compound at 600 and 1000 micromol l(-1) were determined to
      be 72.63+/-10.17% and 81.34+/-4.39%, respectively. This represented an
      approximate 3-folds increase in percentage recovery compared to that of the
      manual small-scale purification process. It was also found that the C.V.% of
      recovery were less than 15% at both concentration levels. The development of this
      automated method was found to be straightforward. The importance and implications
      of this study were discussed.

PMID- 12062673
TI  - Determination of fenoterol in human plasma by HPLC with fluorescence detection
      after derivatization.
AB  - A new method for the determination of fenoterol is described, which uses HPLC
      separation with fluorescence detection. Dobutamine is employed as an internal
      standard. The separation was achieved on a short reversed phase column with a
      mobile phase consisting of water, acetonitrile and methanol. Prior to
      chromatography both analytes are derivatized with 9-chloroformyl-carbazole.
      Isolation of the analytes from plasma is carried out by liquid-liquid extraction
      into 2-butanol after protein precipitation with acetonitrile. The method is
      capable of estimating fenoterol concentrations in the sub-nanogram per ml range
      with sufficient accuracy and precision. The determination of fenoterol can now be
      carried out in the average laboratory without radiolabelled material.

PMID- 12062674
TI  - Simultaneous determination of zinc(II), manganese(II) and iron(II) in
      pharmaceutical preparations.
AB  - The applicability of derivative spectrophotometry for simultaneous determination
      of zinc(II), manganese(II) and iron(II) in the form of PAR complexes was
      presented and discussed. Beer's law was obeyed in range 0.025-13 ppm for zinc 1
      20, for manganese and 0.025-0.2 for iron ion. The elaborated method was applied
      successfully for determination of mentioned ions in pharmaceutical preparation
      without previous separation. The error of the determination did not exceed +/-3%.

PMID- 12062675
TI  - Validation of a near-infrared transmission spectroscopic procedure. Part B:
      Application to alternate content uniformity and release assay methods for
      pharmaceutical solid dosage forms.
AB  - NIR analytical methods can be validated to meet the requirement of demonstrating
      that it is suitable for the analysis of the materials for which it is being used.
      Applying previously described protocols for NIR methods to the analysis of two
      types of pharmaceutical products shows that for these products, NIR is suitable
      as an alternate analytical method for assay and for content uniformity.

PMID- 12062676
TI  - Identification by LC/MS(n) of degradates of a novel carbapenem antibiotic in an
      aqueous matrix.
AB  - Increased drug resistance in Staphylcocci and Enterococci to currently available
      antibiotics has significantly limited therapeutic options. Recently, a novel
      carbapenem antibiotic (Compound A) with a releasable side chain adjacent to the
      carbapenem was investigated to combat methicillin- and vancomycin-resistant
      Staphylococci and vancomycin-resistant Enterococci. The major advantage of
      Compound A over existing antibiotics can be attributed to the fact that cleavage
      of the side chain upon beta-lactam ring opening retained anti-bacterial activity
      while expelling the immunodominant epitope of the presumed beta-lactam hapten. In
      this work, LC/MS methods were developed to identify degradates of Compound A in
      an aqueous matrix utilized in assessing product safety and supporting analytical
      method and formulation development. A total of eight significant degradates were
      observed in this Compound A sample by LC/MS(n) and other techniques. Detailed
      structural analysis of degradates based upon LC/MS(n) data and other supporting
      results will be described in this work. Proposed molecular structures were
      confirmed by synthesis and use of authentic standards for several degradates.
      Degradates 1 and 4 were identified as degradates formed through the reversal of
      Michael reaction from Degradate 3 that is apparently formed by hydrolysis.
      Degradates 2 and 8 were found to be Hofmann elimination degradates. Degradates 5
      and 6 are believed to be formed through dimerization of two parent molecules
      followed by the reversal of Michael reaction. Finally, Degradate 7 is attributed
      to a displacement reaction. Potential degradation pathways based upon these
      preliminary studies will also be discussed.

PMID- 12062677
TI  - Development and application of an analytical method for the determination of
      squalene in formulations of anthrax vaccine adsorbed.
AB  - Specific lots of Anthrax Vaccine Adsorbed, administered to members of the US
      Armed Forces, have been described on various Internet sites and in news articles
      as a source of squalene, a chemical purported by these media to be associated
      with the Gulf War Syndrome. We have developed and validated a method using high
      performance liquid chromatography with ultraviolet detection for the
      determination of squalene in anthrax vaccine preparations. The method has a limit
      of detection of 140 parts per billion and has been successfully applied to a
      commercial vaccine known to contain squalene. We have applied this method to 17
      lots of Anthrax Vaccine Adsorbed administered to members of the US Armed Forces.
      No squalene has been detected in any lot. The results of these analyses provide
      direct evidence for the absence of squalene as an ingredient or a manufacturing
      contaminant in Anthrax Vaccine Adsorbed.

PMID- 12062678
TI  - Determination of the binding parameter constants of Renagel capsules and tablets
      utilizing the Langmuir approximation at various pH by ion chromatography.
AB  - Sevelamer hydrochloride is a cross-linked polymeric amine; it is the active
      ingredient in Renagel capsules and tablets. Sevelamer hydrochloride is indicated
      for the control of hyperphosphatemia in patients with end-stage renal disease.
      The binding parameter constants of sevelamer hydrochloride were determined using
      the Langmuir approximation for three different dosage forms at pH 4.0, 5.5 and
      7.0. The three dosage forms were Renagel 403 mg capsules, Renagel 400 mg tablets
      and Renagel 800 mg tablets. The results demonstrate the equivalency of all three
      dosage forms at each pH. The results also demonstrate a shift in the binding
      mechanism from pH 4.0 to 7.0.

PMID- 12062679
TI  - Study of the stability of polymyxins B(1), E(1) and E(2) in aqueous solution
      using liquid chromatography and mass spectrometry.
AB  - Polymyxins B(1), E(1) (colistin A) and E(2) (colistin B) were subjected to
      degradation in aqueous solutions of different pH values (1.4, 3.4, 5.4 and 7.4)
      and at different temperatures (37, 50 and 60 degrees C) in order to investigate
      the characteristics of decomposition. The progress of decomposition was followed
      by reversed-phase liquid chromatography on YMC-Pack Pro, C-18 stationary phase.
      The degradation curves showed (pseudo) first order kinetics. The pH-rate profiles
      indicate that colistin is more susceptible to degradation in solutions of pH
      above 5 and is more stable in acidic media. The degradation of polymyxin B(1) was
      most rapid at pH 7.4. Qualitative analysis of the degradation products by LC/MS
      reveals that racemization is the major mechanism of degradation in both acidic
      and neutral media.

PMID- 12062680
TI  - Analysis of a formulation containing lincomycin and spectinomycin by liquid
      chromatography with pulsed electrochemical detection.
AB  - A reversed phase ion-pair liquid chromatographic method using a base deactivated
      column and pulsed electrochemical detection on a gold electrode is described. It
      allows the separation of a mixture of spectinomycin sulfate, lincomycin
      hydrochloride and their related substances. A step gradient was necessary to
      obtain a good separation together with a reasonable analysis time of 40 min. The
      mobile phases consisted of an aqueous solution of 3.3 or 0.55 g/l pentanesulfonic
      acid, 10 mM acetic acid and 20 ml/l tetrahydrofuran. Both mobile phases were
      adjusted to pH 4.0 with diluted sodium hydroxide. The influence of the different
      chromatographic parameters on the separation was investigated. Two commercial
      samples were analyzed using the described method. In total 12 components could be
      separated.

PMID- 12062681
TI  - A sensitive assay for ZD1839 (Iressa) in human plasma by liquid-liquid extraction
      and high performance liquid chromatography with mass spectrometric detection:
      validation and use in Phase I clinical trials.
AB  - A specific and sensitive high performance liquid chromatography method for the
      quantitative determination of ZD1839 ('Iressa') concentrations in treated healthy
      volunteers and patients with cancer has been developed and validated. Plasma
      samples (0.5 ml) were extracted, at basic pH, with methyl-t-butyl ether using
      deuterated ZD1839 as an internal standard. The extracts were chromatographed on
      an Inertsil ODS3 column eluted with acetonitrile/ammonium acetate and ZD1839 and
      the internal standard quantified by mass spectrometric detection. The method was
      validated with respect to linearity, selectivity, precision, accuracy, limit of
      quantification (LOQ), recovery and stability. The precision and accuracy of the
      assay were good and the LOQ was 0.5 ng/ml. The assay has been successfully
      applied to a number of clinical and pharmacokinetic studies and been shown to be
      robust and reliable during routine use.

PMID- 12062682
TI  - Spectrofluorometric determination of naproxen in tablets.
AB  - A rapid, selective, sensitive and simple fluorescence method was developed for
      the direct determination of naproxen in tablets. The tablets were triturated,
      dissolved in either NH(3) or NaOH solution, sonicated, filtered and then direct
      fluorescence emission was read at 353 nm (exciting at 271 nm). In order to
      validate the method the results were compared with those obtained by the USP XXIV
      NF 19 Pharmacopeia reference method (high performance liquid chromatography). The
      slope, intercept and variances which are associated with the regression
      coefficient calculated with bivariate least square (BLS) regression indicate that
      both methods are statistically comparable. The recoveries were excellent, except
      in tablets containing the antibiotic tetracycline. In this latter case a
      correction procedure is necessary.

PMID- 12062683
TI  - Derivative spectrophotometric determination of droperidol in presence of
      parabens.
AB  - We have developed a fast and accurate method for the determination of droperidol
      in the presence of methylparaben and propylparaben using derivative
      spectrophotometry. The first derivative amplitudes at 255.2 nm were selected for
      the assay. Calibration graph follows Beer's law in the range of 5-35 microg ml(
      1). The coefficient of variation (CV) for intra-day and inter-day precision were
      less than 1.0 and 2.0%, respectively. The method was applied in the quality
      control of commercial oral and injection solutions and proved to be suitable for
      routine analysis.

PMID- 12062684
TI  - Potentiometric determination of famotidine in pharmaceutical formulations.
AB  - Two new potentiometric methods for determination of famotidine in pure form and
      in its pharmaceutical tablet form are developed. In the first method, the
      construction of plasticised poly(vinyl chloride) (PVC) matrix-type famotidine ion
      selective membrane electrode and its use in the potentiometric determination of
      famotidine in pharmaceutical preparations are described. It is based on the use
      of the ion-associate species, formed by famotidine cation and tetraphenyl borate
      (TPB) counterion. The electrode exhibited a linear response for 1 x 10(-3)-1 x
      10(-5) M of famotidine solutions over the pH range 1-5 with an average recovery
      of 99.26% and mean standard deviation of 1.12%. Common organic and inorganic
      cations showed negligible interference. In the second method, the conditions for
      the oxidimetric titration of famotidine have been studied. The method depends on
      using lead(IV) acetate for oxidation of the thioether contained in famotidine.
      The titration takes place in presence of catalytic quantities of potassium
      bromide (KBr). Direct potentiometric determination of 1.75 x 10(-2) M famotidine
      solution showed an average recovery of 100.51% with a mean standard deviation of
      1.26%. The two methods have been applied successfully to commercial tablet. The
      results obtained reveal good percentage recoveries, which are in good agreement
      with those obtained by the official methods.

PMID- 12062685
TI  - Levels of specific antibodies towards the major antigenic determinant of slime
      producing Staphylococcus epidermidis determined by an enzyme immunoassay and
      their protective effect in experimental keratitis.
AB  - Staphylococcus epidermidis is an important cause of bacterial keratitis. Certain
      S. epidermidis strains produce an extracellular slime layer rich in an acidic
      polysaccharide with a molecular size of 20 kDa (20-kDa PS). We have demonstrated
      that the level of 20-kDa PS-specific antibodies significantly rises after
      establishment of slime-producing S. epidermidis bacteraemia and, furthermore,
      that rabbit polyclonal antibodies to 20-kDa PS opsonize cells of slime-producing
      S. epidermidis to a great degree and promote their clearance by polymorphonuclear
      cells (Arch. Biochem. Biophys. 342 (1997) 389; J. Pharm. Biomed. Anal. 22 (2000)
      1029). The purpose of this study was to examine the protective and therapeutic
      effects both of active immunization, using 20-kDa PS as antigen, and of passive
      administration of specific antibodies towards the 20-kDa PS in a rabbit keratitis
      model. For active immunization, 20 rabbits were subcutaneously immunized with 20
      kDa PS, whereas for passive immunization specific polyclonal IgG antibodies
      against 20-kDa PS were administered to 20 rabbits 1 day before induction of
      infection. Clinical observations were made weekly for 1 month and levels of 20
      kDa PS antibodies in serum and aqueous humor in both immunization groups were
      determined by an enzyme immunoassay. The levels of specific anti-20-kDa PS IgG in
      serum and aqueous humor following either active or passive immunization were
      significantly higher as compared with control groups (P<0.001). Although,
      actively immunized rabbits showed significantly less corneal damage than control
      animals, passively immunized ones were significantly better protected as compared
      with both control and those actively immunized. Obtained results suggest that 20
      kDa PS plays crucial role in the pathogenesis of S. epidermidis keratitis and
      that both types of immunization significantly protect against corneal S.
      epidermidis pathology and damage.

PMID- 12062686
TI  - Characterization of gamma irradiated petrolatum eye ointment base by headspace
      gas chromatography-mass spectrometry.
AB  - The effects of gamma irradiation on petrolatum eye ointment base (EOB) and its
      ingredients (white petrolatum, liquid paraffin, and wool fat) were studied at
      different irradiation doses. Forty-one volatile radiolysis products were detected
      and identified by a combined system of headspace-gas chromatography-mass
      spectrometry (HS-GC-MS). The characteristics of the radiolysis products and the
      degradation pathway were discussed in each case, respectively. GC method
      demonstrates that the component distribution patterns of eye ointment as well as
      its individual ingredients have no differences before and after gamma
      irradiation. The influence of gamma treatment on EOB was quantitatively
      determined at 15, 25 and 50 kGy. The concentrations of the radiolysis products
      increase linearly with increasing doses. Both qualitative and quantitative data
      show that irradiated eye ointment is safe for human use.

PMID- 12062687
TI  - Novel coupling reagents for the sensitive spectrophotometric determination of
      nimesulide in pharmaceutical preparations.
AB  - Novel coupling reagents are used for the sensitive spectrophotometric
      determination of nimesulide (NIME) in either pure form or in its pharmaceutical
      preparations. The methods are based on the diazotisation of reduced NIME,
      followed by either coupling with alcoholic iminodibenzyl (IDB) in acid medium to
      give a deep blue coloured product (lambda(max) of 600 nm) or coupling with 3
      aminophenol (AP) in acid medium to produce an orange red coloured product
      (lambda(max) of 470 nm). Both the methods are highly reproducible and have been
      applied to a wide variety of pharmaceutical preparations and the results compare
      favourably with the reported method. Common excipients used as additives in
      pharmaceutical preparations do not interfere in the proposed methods.

PMID- 12062688
TI  - Determination of melatonin in galenic preparations by LC and voltammetry.
AB  - The amount of melatonin in galenic tablets was determined by means of two
      feasible and accurate analytical methods. The high performance liquid
      chromatography (HPLC) with ultraviolet detection at 223 nm used a C(18) reversed
      phase column; the linear scan voltammetric procedure (LSV) employs a pH 3.0
      phosphate buffer as the supporting electrolyte for the oxidation process of
      melatonin, which has a current intensity maximum at +850 mV. The two methods gave
      satisfactory results in terms of precision and accuracy. In fact, the data of
      repeatability and intermediate precision expressed as percentage relative
      standard deviations (RSD%) were < or =2.8 and the accuracy values, resulting from
      recovery experiments, were between 99.0 and 101.3%. Both methods are suitable for
      quality control of melatonin in galenic preparations; the LSV procedure is more
      rapid, the HPLC method is more sensitive and more precise.

PMID- 12062689
TI  - Determination of theophylline and ephedrine HCL in tablets by ratio-spectra
      derivative spectrophotometry and LC.
AB  - Two methods are described for the determination of theophylline (THP) and
      ephedrine hydrochloride (EPH) in combined pharmaceutical tablet forms. The first
      method depends on the use of the first derivative of the ratio-spectra obtained
      by dividing the absorption spectrum of binary mixtures by a standard spectrum of
      one of the compounds. The first derivative amplitudes at 231.8 and 250.3 nm were
      selected for the assay of THP and EPH, respectively. Calibration graphs were
      established for 20-180 microg ml(-1) for THP and 10-50 microg ml(-1) for EPH. The
      second method is based on high-performance liquid chromatography on a reversed
      phase column using a mobile phase of methanol-water (40+60,v/v) (pH 3) with
      detection at 217 nm. Linearity was obtained in the concentration range of 5-150
      microg ml(-1) for THP and 15-75 microg ml(-1) for EPH. The detection limits for
      THP and EPH were 0.73 and 0.92 microg ml(-1) by ratio-spectra derivative
      spectrophotometry and 0.59 and 0.86 microg ml(-1) by HPLC, respectively. The
      proposed methods were successfully applied to the determination of these drugs in
      laboratory-prepared mixtures and in tablets. The relative standard deviations
      were found to be less than 1.5%, indicating reasonable repeatibility of both
      methods.

PMID- 12062690
TI  - Determination of irbesartan in the presence of hydrochlorothiazide by derivative
      spectrophotometry.
AB  - A first-derivative spectrophotometric method for the determination of irbesartan
      (IRB) alone and in the presence of hydrochlorothiazide (HCT) is described.
      Measurements are made at the zero-crossing wavelength at 263.0 nm for IRB. The
      calibration graph was linear over the range 1.0-12.0 mg l(-1) of IRB, detection
      limit was 0.15 mg l(-1). HCT, in the presence of IRB was determined by direct
      spectrophotometric method at 317 nm. The calibration graph was linear over the
      range 2.0-50.0 mg l(-1) of HCT, detection limit was 0.25 mg l(-1). The proposed
      methods were successfully applied to the determinations of IRB and HCT in
      combined tablets.

PMID- 12062691
TI  - Some kinetic aspects in the immunoradiometric assay of insulin-like growth factor
      binding protein-3.
AB  - In this article the kinetics of the insulin-like growth factor binding protein-3
      (IGFBP-3) reaction with its specific antibody immobilised on the inner wall of
      the reaction tube, and the subsequent binding of the immunocomplex formed with a
      second (125)I-labelled antibody are described. These reactions are used in the
      immunoradiometric determination of IGFBP-3. Independent variables were analyte
      and labelled antibody, temperature, viscosity, and the ionic strength of the
      medium. For the global process mono-exponential kinetics were found to be
      dependent on the concentrations, such dependence fitting with the models
      discussed in this paper. Viscosity results clearly indicate its negative
      influence on the direct reaction rate. Ionic strength shows noticeable but not
      too relevant effects, which suggests that the variation caused by the glycerol
      addition is not due to the influence of the dielectric constant of the solutions
      used. The effect of temperature shows activation parameters similar to the
      viscous flow energy of water, which suggests diffusion control for the global
      process.

PMID- 12062692
TI  - The isomeric metabolites of doxepin in equine serum and urine.
AB  - Due to its tranquilizing properties, the tricyclic antidepressant doxepin may be
      misused as a doping agent in competition horses. Therefore, efficient analytical
      procedures are required to detect this drug in samples submitted for doping
      control. To screen for parent doxepin in equine blood and urine, a less specific
      method has been accepted employing gas chromatography (GC) combined with electron
      impact (EI) mass spectrometry (MS). The aim of this study was identification of
      doxepin metabolites providing more specific MS data to verify positives resulting
      from screening. Thus, after a horse was given doxepin-HCl (1 mg/kg, i.v.), blood
      and urine were analyzed for free or conjugated metabolites using GC combined with
      EI- and positive chemical ionization (PCI) MS. In both of the sample materials,
      cis- and trans-isomers of desmethyldoxepin were detected for up to 48 h after
      treatment using trifluoracetylation and GC/EI-MS. Following enzymic hydrolysis of
      urine and propionylation of extracts, each four isomers of hydroxy
      desmethyldoxepin and hydroxydoxepin were recovered for up to 24 and 48 h,
      respectively. These compounds were characterized by their EI- and PCI-mass
      spectra. Although distinct positions of the hydroxyl groups could not be
      determined, the presence of each two cis/trans-isomeric pairs of differently
      monohydroxylated metabolites may be assumed. Results reported here suggest, that
      screening horses for parent doxepin should be completed by analysis of its major
      isomeric metabolites, desmethyldoxepin and hydroxydoxepin, providing MS data
      specific enough for confirmatory analysis.

PMID- 12062693
TI  - Simultaneous determination of riboflavin phosphate and other ingredients in a
      multivitamin pharmaceutical preparation by on-line automated LC coupled with pre
      column immobilized enzyme reactor.
AB  - An automated chromatographic detection system for the simultaneous determination
      of riboflavin phosphate, caffeine, nicotinamide and pyridoxine hydrochloride in a
      multivitamin pharmaceutical preparation was constructed. Hydrolytic pretreatment
      of riboflavin phosphate to riboflavin was carried out using a pre-column enzyme
      reactor, in which immobilized sweet potato acid phosphatase was packed, and then
      enzymatically hydrolyzed riboflavin and other ingredients in the pharmaceutical
      preparation were concentrated in an ODS trap column. The concentrated riboflavin
      and other ingredients were back-eluted from the trap column using a mobile phase
      containing 1-decanesulfonate as an ion-pair reagent, and then subsequently
      chromatographed on an ODS analytical column. It was necessary to wash the ODS
      trap column with aqueous acetonitrile to remove 1-decanesulfonate in the trap
      column, which is advantageous to concentrate the riboflavin and other ingredients
      for the subsequent analysis. The calibration curves for riboflavin phosphate and
      other ingredients were linear over the concentration ranges tested, and
      correlation coefficients for standard curves were 0.9999 for all four
      ingredients. Analytical recoveries of the four ingredients at different levels of
      concentration added to the ordinary pharmaceutical preparation were also in the
      range of 99.1-101.2%. The present method was superior to the ordinary manual and
      batch-wise enzymatic methods in being harmless to the environment, rapid and
      accurate under continuous autoanalysis.

PMID- 12062694
TI  - Identification of mebeverine acid as the main circulating metabolite of
      mebeverine in man.
AB  - The intestinal spasmolytic drug mebeverine is known to undergo fast in vivo
      enzymatic hydrolysis into mebeverine alcohol and veratric acid. A reversed-phase
      HPLC method with coulometric detection was developed in order to assay the
      hitherto unidentified secondary metabolite mebeverine acid. After intake of a
      single oral dose of 405 mg mebeverine hydrochloride in four healthy human
      volunteers, peak plasma concentrations of mebeverine acid were found to be 1000
      fold higher than those of mebeverine alcohol, i.e. approximately 3 microg/ml
      versus 3 ng/ml. The appearance of mebeverine acid in plasma (median T(max)=1.25
      h) as well as its disappearance (median apparent t(1/2)=1.1 h) were rapid. The
      urinary excretion of mebeverine acid within the first 4 h after dosing amounted
      to 67% of the mebeverine dose (median range: 23-107%). Mebeverine acid appears to
      be a valuable marker of oral exposure to mebeverine.

PMID- 12062695
TI  - Trace determination of shiomarin using a hanging copper/amalgam drop electrode.
AB  - The electrochemical behavior of shiomarin (moxalactam; latamoxef sodium) was
      investigated at hanging copper/amalgam drop electrode (HCADE) in HCl-KCl solution
      (pH 1.1). It was found that shiomarin can form complex with Cu(II) and can be
      adsorbed at the electrode surface. The coordination number is 1 and the number of
      transfer electron involved in the reaction is 2. The peak current of the complex
      related to the concentration of shiomarin and was used to determine trace amounts
      of shiomarin in solution. The linear range of determination is from 1.0 x 10(-9)
      to 8.0 x 10(-5) M using differential pulse adsorptive cathodic stripping
      voltammetry (DPAdCSV). The detection limit is about 4.0 x 10(-10) M (t(a)=70 s,
      S/N=3). The method was also applied to the determination of shiomarin in
      injection powder and urine sample with satisfactory results.

PMID- 12062696
TI  - Colourimetric and AAS determination of cephalosporins using Reineck's salt.
AB  - Two simple, accurate, sensitive and selective procedures for the determination of
      eight cephalosporins are described. These procedures are based on the formation
      of ion-pair complexes between the drugs and ammonium reineckate, the formed
      precipitates are quantitatively determined either colourimetrically or by atomic
      absorption spectrometrically. The methods consist of reacting drugs with
      Reinecke's salt in an acidic medium at 25+/-2 degrees. The first colourimetric
      procedure (procedure I) is based on dissolving the formed precipitate with
      acetone, the volume was completed quantitatively and the absorbance of the
      solution was measured at 525 nm against pure solvent blank. Also, the formed
      precipitates on the atomic absorption spectrometric procedure (procedure II) are
      quantitatively determined directly or indirectly through the chromium precipitate
      formed or the residual unreacted chromium in the filtrate at 358.6 nm. The
      optimum conditions for precipitation have been carefully studied. Beer's law is
      obeyed for the studied drugs in the range 5-35 microg ml(-1) with correlation
      coefficients not less-than 0.9989. Both procedures I and II hold well accuracy
      and precision when applied to the analysis of the cited cephalosporins in
      different dosage forms with good recovery percent ranged from 98.7+/-0.90 to
      100.1+/-0.74 without interference from additives.

PMID- 12062697
TI  - Isolation and characterisation of process-related impurities in rofecoxib.
AB  - Two unknown impurities in rofecoxib bulk drug at levels below 0.1% were detected
      by a simple isocratic reverse phase high performance liquid chromatography
      (HPLC). These impurities were isolated from crude sample of rofecoxib using
      reverse phase preparative HPLC. (1)H, (13)C and Mass spectroscopic investigations
      revealed the structures of the impurities as 4-[4-(methylsulphonyl)phenyl]-3
      phenyl-5-hydroxyfuran-2-one (I) and 4-[4-(methylsulphonyl)phenyl]-3-phenyl-2,5
      furandione (II), respectively. These structures were further confirmed by
      prepared synthetic standards of the impurities. The tentative mechanism for the
      formation of these impurities was discussed.

PMID- 12062698
TI  - Spectroelectrochemical study of the interaction between antitumor drug daunomycin
      and DNA in the presence of antioxidants.
AB  - Anthracycline drug daunomycin (DNR) is a widely used clinical drug. But its side
      effects, especially cardiotoxicity, have greatly restrained its application. The
      side effects were due to free radical formation in the metabolic process of DNR.
      The purpose of this study is to diminish the side effects by using antioxidants.
      Two kinds of free radical scavengers have been investigated, that is, vitamins:
      vitamin C (V(C)), rutin (V(P)) and vitamin B6 (V(B6)); amino acids: cysteine
      (CysH) and methionine (Met). Free radical scavenging efficiency (E degrees (eff))
      of these antioxidants had been calculated. Under the experimental condition, the
      values of E degrees (eff) of V(C), V(P), V(B6), CysH and Met were 23.8, 15.3,
      6.4, 48.2 and -7.7%, respectively. The relationship between the free radical
      scavenging activities and its chemical structure has also been discussed.

PMID- 12062699
TI  - Chemometric resolution of a mixture containing hydrochlorothiazide and amiloride
      by absorption and derivative spectrophotometry.
AB  - Four chemometric techniques, classical least squares (CLS) and inverse least
      squares (ILS) and principal component regression (PCR) and partial least squares
      regression (PLSR) were applied to the absorption and derivative
      spectrophotometric determinations of amiloride and hydrochlorothiazide in a
      pharmaceutical preparation. Four chemometric calibrations for both zero-order and
      first derivative spectra were constructed by measuring the absorbance and their
      dA/dlambda values at 34 points in the wavelength range 205-395 nm for a training
      set containing 2-10 microg/ml amiloride and 4-28 microg/ml hydrochlorothiazide
      corresponding to 25 point mixture design. The building chemometric calibrations
      were confirmed by using the synthetic mixtures containing two drugs. The results
      obtained by the proposed techniques based on the use of the measurements at the
      absorption spectra and at the first derivative spectra were statistically
      compared with each other.

PMID- 12062700
TI  - Direct injection of aqueous samples in packed column supercritical fluid
      chromatography of isosorbide-5-mononitrate from drug release testing.
AB  - A method for the analysis of aqueous samples of isosorbide-5-mononitrate (5-ISMN)
      is presented. It is based on packed column supercritical fluid chromatography
      (SFC) using 20% of 2-propanol in carbon dioxide as the mobile phase and a diol
      silica column as the stationary phase. Using the described conditions it is
      possible to quantitate 5-ISMN released from Imdur tablets in gastric media. The
      precision upon repeated injections was 2% (RSD) at the 20 microg/ml level (n=8),
      using peak height measurements, when the solution was circulated through the
      sample loop of the injector. Samples from drug release testing that had been
      analyzed with reversed phase LC were analyzed with the present method and the
      results agreed well. It is also possible to monitor the drug released in a
      dissolution-testing vessel through direct on-line continuous loading
      (recirculation) of the sample loop of the SFC instrument.

PMID- 12062701
TI  - Determination of bronopol and its degradation products by HPLC.
AB  - Bronopol (2-bromo-2-nitropropane-1,3-diol) is widely used as an anti-microbial in
      cosmetics, external medicaments, shampoos and bath preparations. A reversed-phase
      high performance liquid chromatographic separation method with UV
      spectrophotometric detection was developed for the determination of bronopol and
      its degradation products. Degradation of bronopol was observed in aqueous medium,
      giving rise to non-reproducible data. To overcome this problem, HPLC grade
      methanol (water content <0.05%) was used for sample preparation. In addition, the
      parameters for the HPLC analysis of bronopol were optimised. It was found that
      bronopol standards and product samples were stable in methanol for at least 1
      month at ambient temperature, thus allowing a quantitative and reproducible
      determination of bronopol.

PMID- 12062702
TI  - Cardiac sodium and calcium channels: a history of excitatory currents.
AB  - The entire concept of ion channels as molecular machines to gate ion traffic
      across the membrane has only recently been generally recognized, even though ion
      channels are found in almost all cells. Na+ and Ca2+ channels are the basis of
      excitability, and in the heart they generate the rhythm, coordinating and
      controlling cardiac contraction. Dysfunction of ion channels results in
      arrhythmias that underlie 20-25% of deaths in the developed world, and some
      arrhythmias result directly from gene defects in ion channels. This is my
      personal perspective on the critical ideas and the pioneers in the field of
      cardiac Na+ and Ca2+ channels.

PMID- 12062703
TI  - Dedifferentiation of atrial cardiomyocytes: from in vivo to in vitro.

PMID- 12062704
TI  - Mast cells feel the strain.

PMID- 12062705
TI  - The wnt-frizzled cascade in cardiovascular disease.

PMID- 12062706
TI  - Pharmacological possibilities for protection against myocardial reperfusion
      injury.
AB  - Reperfusion through thrombolysis or percutananeous coronary angioplasty is
      standard treatment in impending acute myocardial infarction. Although restoration
      of blood flow to the jeopardised myocardial area is a perquisite for myocardial
      salvage, reperfusion itself may lead to accelerated and additional myocardial
      injury beyond that generated by ischemia alone. This is referred to as the
      "reperfusion injury". Since the reperfusion injury is initiated by the treatment
      of myocardial infarction, it is of importance to limit the extent of the injury.
      Several studies aimed at preventing reperfusion injury by means of
      pharmacological agents have therefore been conducted. The design of such studies
      is crucial for the results. Factors of importance are the timing of drug
      administration, animal species used, the degree of collateral flow and the
      duration of ischemia. A variety of pharmacological compounds have been
      investigated in different experimental models of myocardial ischemia and
      reperfusion. These include oxygen free radical scavengers, antioxidants, calcium
      channel blockers, inhibitors of neutrophils, nitric oxide, adenosine-related
      agents, inhibitors of the renin-angiotensin system, endothelin receptor
      antagonists, Na(+)/H(+) exchange inhibitors, and anti-apoptotic agents. All these
      groups of pharmacological agents have been demonstrated to protect from
      reperfusion injury determined as limitation of infarct size, improved myocardial
      and endothelial function, and reduced incidence of arrhythmias. The mechanism
      behind the protective effect may differ between different groups of compounds,
      but some compounds may exert cardioprotection via common pathways. Such a pathway
      may be via maintained bioavailability of nitric oxide.

PMID- 12062707
TI  - Dedifferentiation of atrial myocytes during atrial fibrillation: role of
      fibroblast proliferation in vitro.
AB  - OBJECTIVES: Severe myocyte alterations, characterized by enlarged myocytes and
      myolysis, is observed in fibrillating and dilated atria and contributes to atrial
      fibrillation. The aim of this study was to determine the nature of this cellular
      remodeling process and factors involved in its regulation. METHODS: In vivo,
      contractile proteins were studied in 24 human right atrial specimens by means of
      immunohistochemical techniques. In an attempt to reproduce in vitro the myocyte
      remodeling and to study its regulation, human atrial myocytes were cultured
      (n=27) and analyzed immunocytochemically; intracellular Ca(2+) transients (Ca(i)
      tr) in response to electrical stimulation were monitored using Fura-2/AM.
      RESULTS: In diseased specimens, sarcomeres, seen at the periphery of myolytic
      myocytes, stained positively with antibodies against sarcomeric proteins of the Z
      band (alpha-actinin and titin epitope T12) but not with antibodies against titin
      epitope T11 (I-band) or desmin (intermediate filament). beta-myosin heavy chain
      (MHC) and smooth muscle alpha-actin, two proteins of the fetal program, were re
      expressed. In culture, diseased myocytes also showed myolysis and glycogen
      accumulation; their sarcomeres stained positively with anti-alpha-actinin, anti
      T12, anti-beta-MHC and anti-smooth muscle alpha-actin but not with anti-titin T11
      or anti-desmin antibodies. At confluence, myocytes regained a normal sarcomeric
      apparatus and were excitable, as shown by electrical Ca(i)-tr triggering. This
      redifferentiation process was inhibited by fibroblast proliferation. CONCLUSION:
      In diseased atria, myolytic myocytes are in a dedifferentiated state resembling
      that of immature muscle cells. In vitro, fibroblast proliferation prevents the
      reversibility of this cellular alteration.

PMID- 12062708
TI  - Noradrenaline, infused locally, reduces arrhythmia severity during coronary
      artery occlusion in anaesthetised dogs.
AB  - OBJECTIVE: To contribute to the debate, discussed in an earlier issue, regarding
      the role of adrenoceptors in the genesis of early, coronary artery occlusion
      induced ventricular arrhythmias. METHODS: Mongrel dogs anaesthetised with
      chloralose and urethane were given either noradrenaline (NA, 100 ng kg(-1) min(
      1)), phenylephrine (PHE, 200 ng kg(-1) min(-1)) or isoprenaline (ISO 12.5 ng kg(
      1) min(-1)) by intracoronary infusion into a side branch of the left anterior
      descending coronary artery (LAD), commencing 10 min prior to the occlusion and
      then throughout the 25-min occlusion period. Control dogs were infused for the
      same period with saline. In another group of dogs noradrenaline was infused
      intravenously in a dose of 1 and then 2 microg kg(-1) min(-1) over a period of 60
      min, 24 h prior to coronary artery occlusion. Haemodynamic and coronary blood
      flow changes, as well as changes in the epicardial ST-segment and in the degree
      of inhomogeneity were continuously recorded. Ventricular arrhythmias were
      evaluated as ventricular premature beats (VPBs), tachycardiac (VT) episodes and
      the incidences of VT and ventricular fibrillation (VF) during occlusion and
      following reperfusion. RESULTS: Compared to the controls, NA markedly reduced the
      severity of ventricular arrhythmias resulted from coronary artery occlusion and
      increased survival (to 40%) following reperfusion; there were no survivors in the
      control group. Noradrenaline released endogenously following guanethidine
      administration was also protective. Protection was also seen, although to a
      lesser extent with intracoronary PHE (occlusion VF 20% cp 80% in controls;
      survival 42%). In contrast, ISO enhanced arrhythmia severity; five out of seven
      dogs infused with ISO fibrillated within 10 min of the commencement of occlusion
      and no dog survived reperfusion. Other indices of ischaemia severity (epicardial
      ST-segment and inhomogeneity) were also reduced by NA and by PHE. NA, infused 24
      h prior to occlusion was also protective against ischaemia and reperfusion
      induced arrhythmias and ischaemia-induced changes in inhomogeneity. CONCLUSION:
      We conclude that exogenously administered NA, or released endogenously by
      chemical means, reduces the severity of ischaemia and reperfusion-induced
      ventricular arrhythmias and that this is mediated by alpha-adrenoceptors, perhaps
      through presynaptic inhibition of local NA release or by a 'preconditioning'
      effect presumably mediated by PKC.

PMID- 12062709
TI  - Changes in cardiac myocyte morphology alter the properties of voltage-gated ion
      channels.
AB  - OBJECTIVE: The goal of this study was to determine if the properties of the
      transient outward potassium (I(to)), TTX-resistant sodium (I(Na)) and L-type
      calcium (I(Ca)) currents are altered during changes in cardiac cell shape.
      METHODS: Ventricular myocytes were isolated from 3- to 4-day-old neonatal rats
      and cultured on either non-aligned or aligned collagen thin gels. In contrast to
      the flat, stellar-shaped myocytes obtained when the cells are plated on non
      aligned collagen gels, myocytes plated on aligned gels display an elongated, rod
      like shape. Ion channel expression was measured using the whole-cell arrangement
      of the patch clamp technique and Western blot analysis. RESULTS: Peak values for
      I(to), I(Na) and I(Ca) were 9+/-1, 71+/-13 and 7+/-1 pA/pF, respectively, in the
      flat cells, and increased to 21+/-2, 190+/-26 and 13+/-1 pA/pF, respectively, in
      the aligned cells. Application of forskolin (2 microM) and 3-isobutyl-1
      methylxanthine (100 microM) resulted in a 101+/-18% increase in I(Ca) in the flat
      cells, but increased the current by only 43+/-9% in the aligned cells. Internal
      dialysis of the myocytes with cAMP strongly increased the peak I(Ca) in the flat
      cells, but caused no significant change in the aligned cells. While both basal
      and forskolin-stimulated levels of cAMP were the same in the two cell
      morphologies, the expression of the calcium channel alpha(1C) subunit was
      increased in the aligned cells. CONCLUSIONS: The expression and regulatory
      properties of voltage-gated calcium channels are modified during changes in
      neonatal rat myocyte shape.

PMID- 12062711
TI  - Recovery of coronary function and morphology during regression of left
      ventricular hypertrophy.
AB  - OBJECTIVES: To investigate changes in coronary morphology and haemodynamic
      function during regression of established left ventricular hypertrophy (LVH)
      following surgical unloading. METHODS: LVH was induced in guinea-pigs by aortic
      banding and sham operated animals served as controls. We examined the degree of
      LVH, coronary haemodynamic function and contemporaneous vessel morphology 42 days
      post-operation. Identically treated animals were debanded and the same parameters
      measured after 1, 3 and 6 weeks to assess haemodynamic and morphological changes
      as hypertrophy regressed. RESULTS: Banding resulted in an aortic pressure
      gradient of 41+/-9 mmHg and increases in heart/body weight ratio (46%), myocyte
      size (26%) and a doubling of arteriolar wall thickness, all P<0.01. These changes
      were accompanied by a reduction in coronary reserve (38%) and significantly
      (P<0.01) decreased maximal response to acetylcholine (70%), sodium nitroprusside
      (87%), adenosine (70%) and reactive hyperaemia (52%). Surgical debanding
      normalised the systemic haemodynamics and removed the aortic gradient after 7
      days. There was some limited improvement in coronary structure and, to a lesser
      extent, function despite the continued presence of significant LVH. This had
      completely regressed to normal levels 23 days after debanding and was accompanied
      by normalisation of coronary structure and function, although systolic impedance
      to flow remained significantly increased. After 44 days, debanding resulted in
      complete cardiac morphological and functional recovery. CONCLUSION: Left
      ventricular haemodynamic unloading can result in complete normalisation of LVH,
      coronary morphology and haemodynamic function. Although morphological and
      functional recovery were closely correlated, recovery of coronary morphology and
      function slightly preceded that of the myocardium in this aortic banded/debanded
      model.

PMID- 12062710
TI  - Myocardial stiffness is determined by ventricular fibrosis, but not by
      compensatory or excessive hypertrophy in hypertensive heart.
AB  - OBJECTIVES: Diastolic dysfunction that determines symptoms and prognosis in
      patients with systolic dysfunction causes heart failure even in the absence of
      systolic dysfunction. Our recent studies have suggested that myocardial
      stiffening is likely to play a crucial role in triggering deleterious cardiac
      disorder. This study investigated differential contribution of left ventricular
      (LV) hypertrophy and fibrosis to myocardial stiffening in the pressure-overloaded
      heart. METHODS: Dahl-Iwai salt-sensitive rats fed on high-salt diet since 7 weeks
      transit to congestive heart failure at 20 weeks following development of
      hypertension, LV hypertrophy and fibrosis, and 20 such rats were divided into
      three groups: rats treated with angiotensin II type 1 receptor antagonist from 8
      weeks (n=7), rats treated with calcineurin inhibitor from 8 weeks (n=6), and
      untreated rats (n=7). RESULTS: Administration of angiotensin II type 1 receptor
      antagonist and calcineurin inhibitor did not affect blood pressure and allowed
      the development of compensatory hypertrophy. However, in contrast to the
      untreated rats, additive and excessive LV hypertrophy was not observed in either
      of the treated rats. The blockade of angiotensin II kept LV hydroxyproline
      content, a ratio of type I to type III collagen mRNA levels, collagen solubility
      and myocardial stiffness constant at the normal level; however, the calcineurin
      inhibition failed. CONCLUSIONS: Myocardial stiffening may be attributed to
      progressive collagen accumulation, collagen phenotype shift and enhanced collagen
      cross-linking, but not to either compensatory LV hypertrophy or LV hypertrophy
      that progresses from the compensatory stage.

PMID- 12062712
TI  - Abnormalities in myocardial contractility, metabolism and perfusion reserve in
      non-stenotic coronary segments in heart failure patients.
AB  - OBJECTIVE: Myocardial blood flow (MBF) reserve is impaired in congestive heart
      failure (CHF), while fluorine-18-deoxyglucose (18FDG) uptake is relatively
      preserved. To determine whether this mismatch could be interpreted as ischemia,
      we performed dobutamine stress echocardiography (DSE). METHODS: 12 males with
      coronary artery disease (CAD) and CHF were compared with 12 controls with similar
      CAD but normal left ventricular (LV) function. MBF in non-infarct-related artery
      areas was assessed using [(13)N]ammonia positron emission tomography (PET), at
      rest and after dipyridamole infusion and 18FDG uptake was determined. DSE was
      performed with doses up to 40 microg/kg per min. RESULTS: In areas with non
      stenotic arteries MBF reserve was more impaired in CHF patients (1.6+/-0.6 vs.
      2.2+/-0.5; CHF versus normal LV, respectively, P<0.05). MBF reserve was related
      to LV ejection fraction (r=0.6, P<0.05) and wall stress (r=-0.72, P<0.05). PET
      showed mismatch in 4+/-1% of the myocardium in normal LV, compared to 26+/-26% in
      CHF (P<0.05), coinciding with more ischemic wall motion abnormalities on DSE (21
      vs. 4%; CHF versus normal LV, respectively, P<0.05). CONCLUSIONS: In CHF,
      mismatch was found in areas supplied by non-stenotic coronary arteries.
      Corresponding areas showed ischemic wall motions on DSE. These findings suggest
      that the condition of CHF may play a role in perpetuating myocardial failure by
      inducing myocardial ischemia. Follow-up studies to investigate the ischemia-CHF
      relationship in time would be needed.

PMID- 12062713
TI  - Cardiac carbohydrate metabolism in Zucker diabetic fatty rats.
AB  - OBJECTIVE: The aim of this study was to test the hypothesis that, shortly after
      the development of Type-2 diabetes, alterations in cardiac carbohydrate
      metabolism precede the onset of abnormalities in systolic function. METHODS:
      Hearts from 11-week-old Zucker diabetic fatty (ZDF) rats and age matched controls
      were perfused in the isovolumic Langendorff mode with 13C-labeled glucose,
      lactate and pyruvate and unlabeled fatty acids. 13C-Nuclear magnetic resonance
      glutamate isotopomer analysis was carried out to determine the contributions of
      substrates to energy production. RESULTS: The ZDF group was hyperglycemic and the
      relative flux through pyruvate dehydrogenase (PDH) was significantly depressed
      compared to lean controls. In the lean group, lactate, pyruvate and glucose
      contributed 64+/-3, 24+/-3 and 11+/-1%, respectively, to total pyruvate
      oxidation. In the ZDF group, the contribution of glucose both to total pyruvate
      oxidation and to tissue lactate and alanine formation was significantly
      depressed. Cardiac function assessed by the rate-pressure product was similar in
      both groups. The fraction of active PDH was decreased in the ZDF group compared
      to controls (p<0.025). CONCLUSIONS: These results highlight significant changes
      in cardiac carbohydrate metabolism shortly after the development of hyperglycemia
      in a model of Type 2 diabetes in the absence of overt changes in systolic
      function.

PMID- 12062714
TI  - Endothelin A-receptor antagonist administration immediately after experimental
      myocardial infarction with reperfusion does not affect scar healing in dogs.
AB  - OBJECTIVE: Endothelin (ET) receptor antagonists have been reported to reduce both
      infarct size and no-reflow phenomenon; however, in rat models their effect on the
      healing process after myocardial infarction (MI) is controversial. The study
      aimed to evaluate the effect of early administration of the ET(A) receptor
      antagonist darusentan on scar healing in an ischemia-reperfusion model in dogs.
      METHODS: Thirty male mongrel dogs surviving 180 min left anterior descending
      coronary artery balloon occlusion were randomised to: darusentan i.v. bolus-5
      mg/kg 5 min before reperfusion-(group I); darusentan i.v. bolus+chronic oral-10
      mg/kg/day-(group II); saline (group III). Five age-matched dogs served as
      controls (group IV). At 6 weeks weight, volume, mass/volume, wall thickness,
      thinning ratio and expansion index were assessed in the explanted hearts. Infarct
      size and scar area tissue composition were evaluated by computerized
      histomorphometry. Cellularity, vessels and TGFbeta in the scar area were scored
      by immunohistochemistry. RESULTS: 24 dogs (80%; 7 group I, 8 group II, 9 group
      III) developed an anterior MI, transmural in 15 and subendocardial in 9, mean
      size 11.5+/-4% of left ventricular area and 37+/-9% of left ventricular
      endocardial circumference. MIs were homogeneously distributed among the three
      groups regarding either infarct size or transmural extent. No differences were
      found in the three MI groups regarding thinning ratio, expansion index and scar
      area tissue characterization. Percent scar collagen content (37+/-17 vs. 53+/-20
      vs. 46+/-14), myofibroblasts (1.2 vs. 1.3 vs. 1.4), macrophages (1.2+/-0.5 vs.
      1.3+/-0.5 vs. 1.4+/-0.5), neovessels (2.8+/-0.4 vs. 2.6+/-0.5 vs. 2.9+/-0.3) and
      TGFbeta score (2 vs. 2.25 vs. 2.11) were not significantly different.
      CONCLUSIONS: Early administration of the ET(A) receptor antagonist darusentan
      does not affect the scar healing process at 6 weeks after experimental MI with
      reperfusion in dogs.

PMID- 12062715
TI  - Effects of partial ischaemia and volume loading on myocardial efficiency and
      cardiac performance in dogs.
AB  - AIMS AND METHODS: To determine whether volume loading may be beneficial for the
      performance of ischaemic heart, myocardial ischaemia was created by partial
      occlusion of the left anterior descending coronary artery (LAD) to reduce the
      blood flow to 30 approximately 40% of basal level in 11 open chest anaesthetised
      dogs. Global left ventricular function as well as regional performance were
      studied under four different levels of volume loading, euvolemia (EUVO),
      hypervolemia (HYPER), normovolemia and hypovolemia. RESULTS: Left ventricular
      dP/dt(max) and cardiac output were decreased significantly during partial
      occlusion (3511.2+/-425.2 mmHg/s and 0.9+/-0.1 l/min) compared with pre-occlusion
      (4486.5+/-419.2 mmHg/s and 1.3+/-0.1 l/min) (P<0.05). Cardiac work was also
      lowered during partial occlusion (75.4+/-5.2 vs. 106.5+/-2.4 mmHgxl/min)
      (P<0.05). During volume loading, cardiac output and work were elevated (1.2+/-0.2
      l/min and 94.0+/-5.4 mmHgxl/min) compared with EUVO (P<0.05). Local contractile
      dysfunction occurred in the LAD region after partial occlusion. There were no
      significant differences of dysfunction between any conditions of volume loading.
      Percentage shortening of the LAD region was decreased during partial occlusion
      (8.3+/-1.1 vs. 25.0+/-2.7%) and also was higher in HYPER (13.5+/-2.6%) than that
      in EUVO (P<0.05). Partial occlusion and different conditions of volume loading
      did not significantly change the force and local work in the LAD region.
      Myocardial O(2) consumption (MVO(2)) in LAD region was decreased during partial
      occlusion with different levels of volume loading (P<0.05). Local myocardial
      efficiency (work/MVO(2)) was increased during partial occlusion compared with pre
      occlusion (941.3+/-56.2 vs. 551.0+/-65.5 gxmm/ml O(2)/min/100 g, P<0.05) and was
      also higher in HYPER (1208.6+/-48.4 gxmm/ml O(2)/min/100 g) than that in EUVO
      (P<0.05). Local systolic work was decreased during partial occlusion compared
      with pre-occlusion (9.5+/-1.5 vs. 14.2+/-1.3 gxmm/beat), whereas local myocardial
      systolic mechanical efficiency was increased (496.3+/-45.7 vs. 667.2+/-39.8
      gxmm/ml O(2)/min/100 g). There were no significant changes of local systolic work
      and local systolic myocardial efficiency between different volume loading,
      although they tend to be elevated with increasing volume loading. CONCLUSION:
      Increase of blood volume by 15% improved the impaired global performance caused
      by partial occlusion of the LAD in open-chest dogs. This improvement was not
      accompanied by further dysfunction or increased MVO(2) of ischaemic myocardium,
      and therefore might be beneficial without causing further damage to the insulted
      myocytes.

PMID- 12062716
TI  - Coronary patency and its relation to contractile reserve in hibernating
      myocardium.
AB  - OBJECTIVES: Recent clinical studies suggest that contractile reserve may occur in
      a minority of viable, chronically dysfunctional segments with reduced resting
      flow (hibernating myocardium). We hypothesized that epicardial artery patency
      might predict which segments have critically reduced subendocardial flow reserve
      and limited contractile reserve. METHODS: Pigs were chronically instrumented with
      a fixed stenosis on the left anterior descending coronary artery (LAD) to produce
      hibernating myocardium. At least 3 months later, flow at rest and during
      adenosine vasodilation (microspheres), ventricular function and contractile
      reserve (contrast ventriculography), and (18)F-2-deoxyglucose (FDG) deposition
      (ex vivo tissue counting) were quantified. RESULTS: Hibernating myocardium
      (regional dysfunction with reduced resting perfusion) was present in animals with
      an occluded (n=40) or patent (n=19) LAD. Viability was confirmed by histology and
      FDG deposition. In collateral-dependent hibernating myocardium, subendocardial
      flow did not increase above baseline levels during epinephrine or adenosine
      stimulation, consistent with exhausted subendocardial flow reserve at rest. This
      was associated with limited contractile reserve and regionally increased FDG
      deposition. In contrast, subendocardial flow reserve was present in hibernating
      myocardium distal to a patent artery. Contractile reserve during epinephrine
      infusion in this group was significantly greater than in animals with an occluded
      artery. CONCLUSIONS: The physiology and metabolism of hibernating myocardium was
      dependent upon stenosis severity and its effects on subendocardial flow reserve.
      In collateral-dependent hibernating myocardium, contractile reserve was limited
      in the setting of exhausted subendocardial flow reserve, thus supporting the
      hypothesis that metabolic imaging may be preferable for determining viability
      distal to a complete occlusion.

PMID- 12062717
TI  - Sodium accumulation during ischemia induces mitochondrial damage in perfused rat
      hearts.
AB  - OBJECTIVE: The present study aimed to elucidate the involvement of sodium
      overload and following damage to mitochondria during ischemia in the genesis of
      ischemia/reperfusion injury of perfused rat hearts. METHODS: Isolated, perfused
      hearts were exposed to different durations (15-35 min) of ischemia followed by 60
      min reperfusion. At the end of ischemia or reperfusion, myocardial sodium and
      calcium contents and myocardial high-energy phosphates were determined. The
      cardiac mitochondrial ability to produce ATP was measured using saponin-skinned
      bundles. The effects of sodium on the mitochondrial membrane potential and the
      oxidative phosphorylation rate were examined using isolated mitochondria from
      normal hearts. RESULTS: Post-ischemic recovery of left ventricular developed
      pressure decreased in an ischemic duration-dependent manner. Ischemia induced an
      increase in myocardial sodium, but not calcium. This increase was dependent on
      the duration of ischemia. The oxygen consumption rate of skinned bundles from the
      ischemic heart decreased at the end of ischemia. Incubation of mitochondria with
      various concentrations of sodium chloride or sodium lactate in vitro resulted in
      a depolarization of mitochondrial membrane potential and a decrease in ATP
      generating activity. This decrease was not restored after elimination of sodium
      compounds. CONCLUSIONS: The present findings suggest that ischemia induces an
      increase in sodium influx from the extracellular space and that accumulated
      sodium may induce irreversible damage to mitochondria during ischemia. This
      mitochondrial dysfunction may be one of the most important determinants for the
      genesis of ischemia/reperfusion injury in perfused rat hearts.

PMID- 12062718
TI  - Acute stress induces cardiac mast cell activation and histamine release, effects
      that are increased in Apolipoprotein E knockout mice.
AB  - OBJECTIVES: Cardiac mast cells have recently been found to be activated in
      atherosclerotic coronary arteries, but no mediator has so far been documented to
      be released from them, nor have they been investigated in Apolipoprotein (Apo) E
      knockout (k/o) mice that develop atherosclerosis. Psychological stress triggers
      acute coronary syndrome, while acute restraint stress stimulates rat cardiac mast
      cells, the main mediator of which histamine is a coronary constrictor. Here, we
      investigated the effect of acute stress on the activation of cardiac mast cells
      morphologically, as well as the levels of cardiac and serum histamine in normal
      and genetically deficient mice. METHODS: Male, 8-14 week-old ApoE k/o mice and
      their corresponding control C57BL/6J mice were used. Significant reduction of
      cardiac histamine from 396.7+/-45.6 to 214.6+/-41.5 ng/g was observed over 120
      min restraint stress with a corresponding increase in serum histamine from
      126.9+/-4.0 to 188.4+/-17.3 ng/ml in C57BL mice. Cardiac mast cell activation was
      observed by light and electron microscopy. Both basal cardiac and serum histamine
      in ApoE k/o mice was significantly higher than that in C57BL mice. Although the
      extent of mast cell activation in ApoE k/o mice was similar to that of C57BL
      mice, the number of cardiac mast cells in ApoE k/o mice was 37% higher. Histamine
      levels were hardly detectable with or without stress in W/W(v) mast cell
      deficient mice. CONCLUSIONS: Acute restraint stress triggered cardiac histamine
      release in mice that was clearly derived from mast cells, as it was absent in
      W/W(v) mice. The high basal cardiac and serum histamine in ApoE k/o mice, along
      with the high number of cardiac mast cells, suggest possible ongoing cardiac mast
      cell activation that may participate in atherosclerosis. These results may
      possibly help better understand stress-related cardiovascular pathology.

PMID- 12062719
TI  - Coronary function and adenosine receptor-mediated responses in ischemic
      reperfused mouse heart.
AB  - OBJECTIVES: To assess the impact of ischemia-reperfusion (I/R) on coronary
      function, and the role of endogenous adenosine in modifying post-ischemic
      vascular function in asanguinous hearts. METHODS: Vascular function was studied
      in Langendorff perfused mouse hearts subjected to 20-25-min ischemia and 30-min
      reperfusion. RESULTS: Ischemia altered the dependence of flow on work-rate
      observed in normoxic hearts, and inhibited reflow by mechanisms additional to
      diastolic compression. Coronary responses were selectively reduced: 2
      chloroadenosine and ADP dilated with pEC(50)s of 8.4+/-0.1 and 7.4+/-0.1 in non
      ischemic hearts versus 7.7+/-0.1 and 7.1+/-0.1 after 20-min ischemia (P<0.05).
      Sensitivity was further reduced after 25-min ischemia. Responses to nitroprusside
      were unaltered. NO-synthase antagonism (50 microM nitro-L-arginine methylester)
      reduced sensitivities to 2-chloroadenosine and ADP up to 10-fold, and eliminated
      inhibitory effects of I/R. K(ATP) blockade with 5 microM glibenclamide impaired
      sensitivity pre- and post-ischemia, not eliminating the inhibitory effects of
      I/R. A(1) adenosine receptor antagonism with 100 nM 8-cyclopentyl-1,3
      dipropylxanthine worsened effects of ischemia on sensitivity. A(2A) adenosine
      receptor antagonism with 100 nM 8-(3-chlorostyryl)caffeine reduced post-ischemic
      flow by 50%, yet paradoxically enhanced post-ischemic contractile recovery.
      CONCLUSIONS: Ischemia modifies vascular control and impairs NO- versus K(ATP)
      dependent coronary dilation in an asanguinous model. Endogenous adenosine
      protects against vascular dysfunction via A(1) receptors, and determines coronary
      reflow via A(2A) receptors. However, intrinsic A(2A) activation apparently
      worsens contractile dysfunction.

PMID- 12062720
TI  - Increased pulmonary prostacyclin synthesis in rats with chronic hypoxic pulmonary
      hypertension.
AB  - OBJECTIVE: The regulation of pulmonary prostacyclin synthesis is not completely
      understood. We tested the hypothesis that prostacyclin production is
      predominantly stimulated by hemodynamic factors, such as increased shear-stress,
      and is thus increased in rats with chronic hypoxic pulmonary hypertension.
      METHODS: To this end, we determined pulmonary prostacyclin synthase (PGIS) gene
      expression, circulating levels of the stable prostacyclin metabolite 6-keto
      prostaglandin F(1alpha) (6-keto-PGF(1alpha)), pulmonary endothelin (ET)-1 gene
      expression, and ET-1 plasma levels in rats exposed to 4 weeks of hypoxia (10%
      O(2)) in the presence or absence of either the nitric oxide (NO) donor
      molsidomine (MD, 15 mg/kg/day) or the ET-A receptor antagonist LU135252 (LU, 50
      mg/kg/day). RESULTS: Right ventricular systolic pressure (RVSP), the cross
      sectional medial vascular wall area of pulmonary arteries, and ET-1 production
      increased significantly during hypoxia. PGIS mRNA levels increased 1.7-fold, and
      6-keto-PGF(1alpha) plasma levels rose from 8.2+/-0.8 to 12.2+/-2.2 ng/ml during
      hypoxia (each P<0.05 vs. normoxic controls). MD and LU reduced RVSP and pulmonary
      vascular remodeling similarly (each P<0.05 vs. hypoxia), but only MD inhibited
      pulmonary ET-1 formation (P<0.05 vs. hypoxia). Nevertheless, both drugs
      attenuated the increase in PGIS gene expression and plasma 6-keto-PGF(1alpha)
      levels (each P<0.05 vs. hypoxia). CONCLUSION: Our data suggest that prostacyclin
      production in hypertensive rat lungs is predominantly increased by hemodynamic
      factors while hypoxia, NO and ET-1 per are less important stimuli, and that this
      increase may serve as a compensatory mechanism to partially negate the hypoxia
      induced elevation in pulmonary vascular tone.

PMID- 12062721
TI  - Aortic smooth muscle cell phenotypic modulation and fibrillar collagen deposition
      in angiotensin II-dependent hypertension.
AB  - BACKGROUND: We investigated the effect of nifedipine, AT-1 and ET-1 receptor
      blockade on arterial smooth muscle cell phenotypes and collagen deposition in
      TGRen2 transgenic rat (TGR). METHODS: Four-week-old TGR were blood pressure (BP)
      matched and allocated to receive a placebo (n=8), the calcium antagonist
      nifedipine (n=6), the AT-1 specific receptor antagonist irbesartan (n=6), the
      ET(A)/ET(B) antagonist bosentan (n=6) or the ET(A)-selective antagonist BMS
      182874 (n=5). Sprague-Dawley normotensive rats served as controls (n=6). After 4
      weeks of treatment animals were euthanized and the left ventricle (LV) and the
      structural changes in intracardiac arterioles and aorta were assessed
      histomorphometrically. Smooth muscle cell phenotypes and fibrillar collagen
      content of the aortic wall were evaluated by immunostaining, using
      differentiation markers-specific antibodies and Syrius red staining,
      respectively. The changes in ET(A) and ET(B) receptor density were also assessed
      with quantitative autoradiography. RESULTS: Compared to placebo, only irbesartan
      lowered BP (P<0.001) and prevented LV and small resistance artery hypertrophy.
      The aorta of placebo-treated TGR showed an increase in foetal-type smooth muscle
      cell content and fibrillar collagen staining, compared to controls. These changes
      were blunted by irbesartan, which increased ET(A) receptors in the arterial wall,
      enhanced by BMS-182874 and unaffected by bosentan. Nifedipine also blunted both
      the VSMC and collagen changes despite having no effect on BP and ET(A) receptors.
      CONCLUSIONS: In TGRen2, vascular hypertrophy entails both smooth muscle cell
      phenotypic modulation and collagen deposition. These alterations do not follow
      closely the BP changes and seem to imply the dihydropyridine-sensitive calcium
      channels.

PMID- 12062722
TI  - Overexpression of endothelial NO synthase induces angiogenesis in a co-culture
      model.
AB  - OBJECTIVE: Angiogenesis is a complex multistep process that involves endothelial
      cell (EC) migration, proliferation and differentiation into vascular tubes. NO
      has been reported to be a downstream mediator in the angiogenic response to a
      variety of growth factors, but the mechanisms by which NO promotes neovessel
      formation is not clear. We hypothesized that NO directly contributes to EC
      migration and capillary tube formation. METHODS: Since previous studies have
      noted important biological differences between NO produced pharmacologically by
      NO-donor compounds compared to that from NO synthase (NOS), we used a cell-based
      gene transfer approach to increase NO production in a co-culture model of in
      vitro angiogenesis. Rat smooth muscle cells (SMCs) were transfected with plasmids
      containing VEGF(121), VEGF(165) (SMC(VEGF)), endothelial NOS (SMC(eNOS)) or the
      empty vector (SMC(Cont)). Expression of the eNOS in SMC(eNOS) was confirmed by
      Northern analysis, NADPH-diaphorase activity, and nitrite/nitrate levels, whereas
      VEGF production was confirmed using ELISA. Calf pulmonary artery ECs (CPAECs)
      were cultured on the fibrin matrix with (co-culture) or without underlying SMCs
      (monoculture). RESULTS: Co-culture of ECs with SMC(Cont) had no effect on EC
      differentiation compared with EC in monoculture (differentiation index, DI=2.8+/
      3.4 vs. 2.1+/-2.8, respectively, NS). In contrast, co-culture with SMC(eNOS)
      resulted in the formation of extensive capillary-like structures within 48 h
      (DI=17.2+/-5.9, P<0.001 versus SMC(Cont)), which was significantly inhibited
      using a NOS inhibitor, L-NAME (3 mM) (DI=4.5+/-3.04, P<0.001 versus SMC(eNOS)).
      Similarly, SMC(VEGF121) induced an angiogenic response (DI=14.2+/-3.8), which was
      also significantly inhibited by L-NAME (DI=5.9+/-1.8, P<0.05). In using the
      Boyden chamber model, SMC(eNOS), but not SMC(Cont) increased EC migration to a
      similar extent as SMC(VEGF121), and both were significantly inhibited with L
      NAME. CONCLUSIONS: These data support an important paracrine role for
      endogenously produced NO in EC migration and differentiation in vitro, and
      suggest that the cell-based eNOS gene transfer may be a useful approach to
      increase new blood vessel formation in vivo.

PMID- 12062723
TI  - Effect of hypoxia and endothelial loss on vascular smooth muscle cell
      responsiveness to VEGF-A: role of flt-1/VEGF-receptor-1.
AB  - OBJECTIVE: The influence of hypoxia and endothelial loss on the responsiveness of
      vascular smooth muscle cells (VSMCs) to vascular endothelial growth factor (VEGF
      A) was tested. METHODS AND RESULTS: Exposure to hypoxia induced a potentiation of
      cultured cell proliferation in response to either the agonist for the VEGF
      receptor 1 (flt-1) placental growth factor (PlGF-1) or to VEGF-A. This effect was
      mediated by the mitogen activated protein kinase (MAPK) cascade, since it was
      inhibited by the MAPK kinase inhibitor PD98059 and by the farnesyl transferase
      inhibitor II. Accordingly, PlGF-1 activated extracellular signal-regulated
      kinase(1/2). In rat aortic rings deprived of endothelium and cultured in three
      dimensional fibrin gels, an increased sprouting of tubular structures in response
      to VEGF-A was observed only under hypoxia. Studies on rat aorta preparations
      revealed an endothelium-dependent vasorelaxation in response to either VEGF-A or
      PlGF1, which was reversed to a contractile response in endothelium-deprived
      preparations exposed to hypoxia. Western blot and immunohistochemistry of
      endothelium-deprived preparations exposed to hypoxia showed flt-1 receptor
      expression in all medial cells. Conversely, flt-1 mRNA, of endothelium-deprived
      aortic preparations and of tubular structures, was unchanged by hypoxia.
      CONCLUSION: These findings demonstrate that experimental conditions mimicking
      pathological vascular injury can make VSMCs responsive to VEGF-A through the
      induction of functional flt-1 receptors.

PMID- 12062724
TI  - Comparison of time of reperfusion during anterior wall acute myocardial
      infarction to left ventricular volume one month and 20 months later.
AB  - We studied 95 patients with a first anterior wall acute myocardial infarction who
      received successful reperfusion within 72 hours after the onset. The patients
      were divided into 4 groups based on the time required to achieve reperfusion; <3
      hours (n = 23), 3 to 6 hours (n = 42), 6 to 24 hours (n = 17), and >24 to 72
      hours (n = 13). The infarct size, as evaluated by thallium-201 single-photon
      emission computed tomography, at 1 month after the infarct was significantly
      larger (p <0.05) in >24 to 72 hours (1,593 +/- 652 U) than that in <3 hours (749
      +/- 650 U), but was not significantly different from that at 3 to 6 hours (1,353
      +/- 770 U) or 6 to 24 hours (1,371 +/- 561 U). The end-diastolic volume index at
      1 month did not differ among the 4 groups. However, the end-diastolic volume
      index during the follow-up period (20 +/- 8 months) in >24 to 72 hours (93 +/- 23
      ml/m(2)) was significantly larger than that in the other 3 groups (<3 hours [65
      +/- 21 ml/m(2)], 3 to 6 hours [65 +/- 22 ml/m(2)], and 6 to 24 hours [70 +/- 25
      ml/m(2)]). Similar findings were observed in end-systolic volume index. In
      conclusion, although infarct size reduction was not observed by late reperfusion,
      left ventricular volumes at 1 month were comparable among patients with
      successful reperfusion within 3 and up to >24 hours. Left ventricular volumes 2
      years after acute myocardial infarction were significantly larger in patients who
      did not under reperfusion for >24 hours.

PMID- 12062725
TI  - Time course and relation to local viability of microvascular function and volume
      after reperfused acute myocardial infarction.
AB  - We assessed the time course of the alterations of microvascular function and
      myocardial perfusion, as well their relation to local inotropic reserve (IR), in
      21 patients who underwent successful primary coronary angioplasty for acute
      myocardial infarction and in whom local myocardial dysfunction persisted at
      hospital discharge. Coronary flow reserve (CFR) and myocardial perfusion were
      assessed immediately after angioplasty, and on day 1 and day 8 by intracoronary
      Doppler and myocardial contrast echocardiography, respectively. Dobutamine
      echocardiography was performed on day 7 for assessment of local IR. After
      angioplasty, CFR was severely altered in patients with (n = 14) and without (n =
      7) IR (1.44 +/- 0.26 and 1.36 +/- 0.21, respectively; p = NS). Among patients
      with IR, CFR increased significantly at day 1 (2.26 +/- 0.62, p <0.005 vs acute
      stage) compared with those without IR (p = NS vs acute). In contrast, the extent
      of microvascular obstruction as defined by contrast echocardiography remained
      unchanged in all patients at day 1 compared with acute measurements.
      Microvascular obstruction decreased at day 8 in the sole subset of patients with
      local IR (p <0.05 vs acute stage). In patients treated by immediate coronary
      angioplasty for acute myocardial infarction, subsequent improvement of myocardial
      perfusion is associated with preexistent recruitable microvascular function in
      the infarct-related artery. The presence of reversible microvascular dysfunction
      at the early stage after acute myocardial infarction is associated with local
      tissue viability in humans.

PMID- 12062726
TI  - Automated regional myocardial displacement for facilitating the interpretation of
      dobutamine echocardiography.
AB  - Quantification of stress echocardiography may overcome the training requirements
      and subjective nature of visual wall motion score (WMS) assessment, but
      quantitative approaches may be difficult to apply and require significant time
      for image processing. The integral of long-axis myocardial velocity is
      displacement, which may be represented as a color map over the left ventricular
      myocardium. This study was designed to explore the feasibility and accuracy of
      measuring long-axis myocardial displacement, derived from tissue Doppler, for the
      detection of coronary artery disease (CAD) during dobutamine stress
      echocardiography (DBE). One hundred thirty patients underwent standard DBE,
      including 30 patients at low risk of CAD, 30 patients with normal coronary
      angiography (both groups studied to define normal ranges of displacement), and 70
      patients who underwent coronary angiography in whom the accuracy of normal ranges
      was tested. Regional myocardial displacement was obtained by analysis of color
      tissue Doppler apical images acquired at peak stress. Displacement was compared
      with WMS, and with the presence of CAD by angiography. The analysis time was 3.2
      +/- 1.5 minutes per patient. Segmental displacement was correlated with wall
      motion (normal 7.4 +/- 3.2 mm, ischemia 5.8 +/- 4.2 mm, viability 4.6 +/- 3.0 mm,
      scar 4.5 +/- 3.5 mm, p <0.001). Reversal of normal base-apex displacement was an
      insensitive (19%) but specific (90%) marker of CAD. The sum of displacements
      within each vascular territory had a sensitivity and specificity of 89% and 79%,
      respectively, for prediction of significant CAD, compared with 86% and 78%,
      respectively, for WMS (p = NS). The displacements in the basal segments had a
      sensitivity and specificity of 83% and 78%, respectively (p = NS). Regional
      myocardial displacement during DBE is feasible and offers a fast and accurate
      method for the diagnosis of CAD.

PMID- 12062727
TI  - Relation of matrix-metalloproteinase 3 found in coronary lesion samples retrieved
      by directional coronary atherectomy to intravascular ultrasound observations on
      coronary remodeling.
AB  - We investigated the relation between the presence of matrix-metalloproteinases
      (MMPs) and direction of remodeling in the coronary lesions of 35 patients.
      Positive arterial remodeling describes a compensatory expansion of the external
      elastic membrane (EEM) area of atherosclerotic lesions. An association between
      positive remodeling and unstable clinical presentation has been previously
      described. However, the pathophysiology of the remodeling process is not
      completely understood. Preinterventional intravascular ultrasound images and
      directional atherectomy (DCA) samples were analyzed. The remodeling ratio was
      calculated as the EEM area at the lesion site divided by the EEM area at the
      proximal reference. Positive, intermediate, and negative remodeling were defined
      as ratios of >1.05, 0.95 to 1.05, and <0.95, respectively. The histologic samples
      were immunostained for MMP-1, -2, -3, and -9. Positive, intermediate, and
      negative remodeling was present in 15, 7, and 13 lesions, respectively. Mild and
      intense cell-associated staining for MMP-1 was found in 21 (68%) and 10 (32%)
      patients, respectively. Staining for MMP-3 was mild in 20 patients (67%) and
      intense in 10 patients (33%). Immunostaining for MMP-2 and -9 was mild in all
      samples. Intense staining for MMP-3 was significantly more common in lesions with
      positive than negative and/or intermediate remodeling (58% vs 17%; p = 0.04; p =
      0.053 after adjustment for gender). Thus, in this in vivo intravascular
      ultrasound and histologic study, increased cell-associated MMP-3 staining was
      associated with positive arterial remodeling.

PMID- 12062728
TI  - Relation of stent design and stent surface material to subsequent in-stent
      intimal hyperplasia in coronary arteries determined by intravascular ultrasound.
AB  - A variety of different stent designs and coatings have become available. This
      study sought to determine the impact of stent design and gold-coating of stents
      on intimal hyperplasia (IH) in human atherosclerotic coronary arteries in
      relation to known predictors of restenosis. Angiographic and intravascular
      ultrasound (IVUS) studies were performed at 6-month follow-up on 311 native
      coronary lesions of 311 patients treated with 99 Multi-Link stents, 74 InFlow
      steel stents, 73 InFlow gold-coated stents, 41 Palmaz-Schatz stents, 12 NIR steel
      stents, and 12 gold-coated NIR Royal stents. Lumen and stent cross-sectional area
      (CSA) were measured at 1-mm axial increments. Mean IH CSA (stent CSA - lumen CSA)
      and mean IH thickness were calculated and averaged over the total stent length.
      IVUS demonstrated different levels of IH for the 6 stents. Mean IH thickness
      ranged from 0.20 +/- 0.13 mm for Multi-Link stents to 0.43 +/- 0.14 mm for InFlow
      goal-coated stents (p <0.001). Multivariate analysis proved non-Multi-Link stent
      design (odds ratio 3.45, 95% confidence intervals 1.13 to 11.11, p <0.034) and
      gold coating (odds ratio 3.78, 95% confidence intervals 1.88 to 7.54, p <0.001)
      to be the only independent predictors of IH thickness >0.3 mm. In conclusion,
      stent design and surface material have an important impact on the IH response to
      stents implanted in human coronary arteries. However, the differences in IH
      thickness between the analyzed stents were relatively small compared with the
      absolute lumen dimensions.

PMID- 12062729
TI  - One-year outcome after combined coronary artery bypass grafting and
      transmyocardial laser revascularization for refractory angina pectoris.
AB  - Long-term outcomes after coronary artery bypass graft surgery (CABG) plus
      transmyocardial revascularization (TMR) are largely unknown. We report the
      results of 30-day and 3-, 6-, and 12-month clinical follow-up after CABG plus TMR
      in a consecutive series of patients with refractory angina pectoris and > or = 1
      myocardial ischemic area not amenable to CABG. All patients who underwent CABG
      plus TMR (n = 169) (mean age 63 +/- 10 years, 70% men, 51% with previous CABG,
      82% were deemed inoperable at other heart surgery centers due to small vessels or
      diffuse disease) between March 1996 and February 2000 were clinically followed
      and end points of interest (survival, stroke, acute myocardial infarction, and
      revascularization) and angina class were recorded at 30 days and 3, 6, and 12
      months after CABG. At 1 year, actuarial survival and event-free survival were 85%
      and 81%, respectively. At the end of the first year after the procedure, 7
      patients (4%) had angina class III/IV versus 152 patients (90%) at baseline (p
      <0.001). Predictors of major adverse cardiac events were advanced age (odds ratio
      [OR] 3.4, 95% confidence intervals [CI] 1.2 to 9.4, p = 0.01), prolonged
      intensive care unit stay (OR 3.3, CI 1.1 to 9.7, p <0.001), new-onset atrial
      fibrillation (OR 2.8, CI 1.1 to 7.0, p = 0.02), and in-hospital myocardial
      infarction (OR 1.5, CI 1.3 to 1.7, p <0.001). Thus, procedural success at 30 days
      and overall event-free and actuarial survival in a high-risk population setting
      shows that CABG plus TMR is a safe revascularization option for patients with
      intractable angina pectoris.

PMID- 12062730
TI  - Predicting revascularization outcome in patients with coronary artery disease and
      left ventricular dysfunction (data from the SEMINATOR study).
AB  - A main goal of revascularization in patients with chronic ischemic cardiomyopathy
      is to improve global left ventricular (LV) function. This study aimed to verify
      whether it is possible to predict an increase in LV ejection fraction (EF) after
      revascularization on the basis of the extent of LV asynergy, myocardial
      viability, and revascularization completeness. We studied 77 patients with
      chronic LV ischemic dysfunction using baseline resting and nitrate-enhanced
      technetium-99m sestamibi single-photon emission computed tomography. Regional
      wall motion and global LVEF were assessed with echocardiography before and after
      revascularization, which was complete in 51 patients and incomplete in 26. The
      number of viable asynergic segments included in revascularized coronary artery
      territories was the strongest predictor of significant (> or = 5 EF U) functional
      improvement in univariate discriminant analysis. According to multivariate
      stepwise discriminant analysis, this parameter, together with the number of
      baseline asynergic segments, allowed the detection of patients with significant
      LVEF improvement with 75% accuracy. With use of a multivariate regression model,
      including the 2 mentioned variables, the measure of postrevascularization LVEF
      increase could be accurately quantified (R(2) 0.43, p <0.000001). In conclusion,
      this study suggests that the severity of baseline asynergy, the extent of
      myocardial viability, and the completeness of revascularization are the main
      determinants of postrevascularization functional recovery in patients with LV
      ischemic dysfunction, and that on the basis of these variables it is possible to
      predict the measure of LVEF increase.

PMID- 12062731
TI  - The liver and lovastatin.
AB  - The cholesterol-lowering agents, known as statins, have been in use for 15 years
      and are among the most commonly prescribed drugs. Animal studies and premarketing
      clinical trials have given signals of hepatotoxicity, primarily minor elevations
      in serum alanine aminotransferase enzyme (ALT) levels. For that reason, all of
      the cholesterol-lowering drugs have labeling that requires monitoring of liver
      enzymes. Postmarketing experience, however, suggests that hepatotoxicity is rare
      and thus it is timely to revisit the issue. The first of the statins, lovastatin,
      was approved in 1986 and has acquired 24 million patient-years of clinical
      experience. Minor elevations in liver enzymes, i.e., ALT 3 x the upper limit of
      normal (ULN) occur in 2.6% and 5.0% of patients on lovastatin doses of 20 and 80
      mg/day, respectively. These elevations are reversible with continuing therapy,
      are dose related, and are probably related to cholesterol lowering per se. Rare
      cases of acute liver failure (ALF) have been reported with all of the cholesterol
      lowering drugs. With lovastatin, the rate is approximately 1/1.14 million patient
      treatment years, which is 9% of the background rate of all causes of ALF and
      approximately equal to the background rate of idiopathic ALF. Monitoring for
      hepatotoxicity has not been effective in preventing serious liver disease,
      largely because of its rarity and the poor predictive value of minor ALT
      elevations. In fact, it may increase patient risk because of needless
      discontinuation of cholesterol-lowering therapy for false-positive results in
      patients who are benefiting from treatment.

PMID- 12062732
TI  - Biatrial multisite mapping of atrial premature complexes triggering onset of
      atrial fibrillation.
AB  - Pulmonary veins are considered to be the most common origin of the focal activity
      that triggers the onset of atrial fibrillation (AF). However, little is known
      about the importance of ectopic activity located outside the pulmonary veins.
      This study included 45 patients (8 women and 37 men, mean age 55 +/- 12 years)
      with paroxysmal (n = 25) and persistent (n = 20) AF in whom multisite mapping of
      the right and left atria was performed using a 64-electrode basket catheter (n =
      21) or a noncontact mapping system (n = 24). Spontaneous or orciprenaline-induced
      atrial premature complexes (APCs) were mapped. In all, 94 AF onsets from 38
      distinct foci in 30 patients were observed and analyzed. Of these foci, 20 (53%)
      were located in pulmonary veins and 18 (47%) were located outside the pulmonary
      veins in other parts of the atria. In 22 patients (73%), AF was reproducibly
      induced by APCs from a single focus (59 episodes). In 8 patients (27%), AF
      originated from 2 distinct foci (35 episodes). Additionally, 20 of 30 patients
      (67%) who developed AF had APCs in different locations not inducing AF. APCs
      inducing AF had shorter coupling intervals than APCs not inducing AF (307 +/- 54
      vs 409 +/- 76 ms, p <0.001). This study showed that 47% of ectopic foci
      triggering the onset of AF were located outside the pulmonary veins in
      extravenous parts of the left atrium and the right atrium, and 27% of patients
      had AF onsets of bifocal origin. These data challenge the current opinion that
      extrapulmonary foci play a minor role in inducing AF.

PMID- 12062733
TI  - Effect of carvedilol on microcirculatory and glucose metabolic regulation in
      patients with congestive heart failure secondary to ischemic cardiomyopathy.
AB  - In a randomized (2:1), double-blinded design study, we studied 25 patients with
      congestive heart failure (66 +/- 9 years, ejection fraction 30 +/- 7%) before and
      after 23-week treatment with the beta blocker carvedilol 25 mg twice daily (n =
      17) or placebo (n = 8) in addition to standard therapy. Using dynamic positron
      emission tomography, myocardial perfusion at rest and perfusion reserve after
      dipyridamole (0.56 mg/kg/min) were measured. Myocardial glucose uptake and plasma
      levels of catecholamines were also estimated. Carvedilol treatment reduced the
      rate-pressure product (8,781 +/- 2,672 vs 6,342 +/- 1,346, p <0.01) and improved
      ejection fraction (29 +/- 7% vs 37 +/- 11%, p <0.001), whereas no changes were
      observed in the control group. Perfusion at rest was unchanged in the placebo
      group (0.81 +/- 0.17 vs 0.86 +/- 0.23 ml/g/min, p = NS), whereas the carvedilol
      treated group showed a significant reduction (0.88 +/- 0.26 vs 0.75 +/- 0.16
      ml/g/min, p <0.05). Dipyridamole-induced hyperemia was significantly reduced
      after carvedilol treatment (1.51 +/- 0.45 vs 1.31 +/- 0.51 ml/g/min, p <0.001),
      whereas myocardial perfusion reserve was unaltered. Carvedilol did not alter
      myocardial glucose uptake (0.33 +/- 0.14 vs 0.32 +/- 0.12 micromol/g/min, p = NS)
      or the plasma catecholamines levels. We therefore conclude that in patients with
      congestive heart failure, carvedilol reduced resting and hyperemic perfusion. No
      effect on glucose uptake or catecholamine levels was observed. The reduced
      perfusion at rest must reflect reduced perfusion demand and thereby a higher
      threshold for myocardial ischemia and protection against myocardial damage or
      malignant arrhythmia. These effects may serve as a pathophysiologic explanation
      for the reduced mortality in patients with congestive heart failure who receive
      carvedilol.

PMID- 12062734
TI  - Clinical, echocardiographic, and biomechanical differences in mitral valve
      prolapse affecting one or both leaflets.
AB  - Mitral valve prolapse (MVP) is the most common cause of severe mitral
      regurgitation necessitating surgical correction. Unileaflet prolapse (ULP),
      usually involving the posterior leaflet, is more common than bileaflet prolapse
      (BLP), which is more difficult to repair. Little is known about clinical,
      echocardiographic, and biomechanical differences between ULP and BLP. In this
      study, biomechanical testing was performed on mitral valve leaflets and chordae
      obtained at operation for severe mitral regurgitation. Preoperative clinical
      characteristics and echocardiographic measurements were obtained on surgical
      patients (ULP = 88, BLP = 37). Men outnumbered women by a factor of 4:1 in ULP,
      and by 3:1 in BLP. Patients with BLP were younger (53.2 +/- 1.7 vs 59.5 +/- 1.1
      years) than those with ULP, and this difference was greater in women (48.9 +/-
      2.5 vs 62.9 +/- 2.2 years). BLP patients were less likely to be hypertensive, and
      more likely to undergo valve replacement rather than repair. Echocardiography
      showed that BLP leaflets were longer and thicker than ULP leaflets. The severity
      of mitral regurgitation was similar in both groups, although ULP patients had a
      much higher incidence of flail leaflets (45% vs 5% in BLP). Mechanical strength
      of chordae was greater in BLP than in ULP, although leaflet strength was similar.
      The increased chordal strength in BLP may be responsible for less flail. In
      patients with MVP and severe mitral regurgitation requiring surgery, ULP and BLP
      are distinct entities with substantial differences in the population affected, in
      echocardiographic manifestations including prevalence of flail, in chordal
      mechanics, and in the likelihood of surgical repair.

PMID- 12062735
TI  - Usefulness of cytokines interleukin-6 and interleukin-2R concentrations in
      diagnosing active infective endocarditis involving native valves.
AB  - The most important diagnostic value in infective endocarditis (IE) is isolation
      of the causative microorganism. Because premature antibiotic treatment is
      commonly administered before the assessment of blood cultures, the percentages of
      isolated microorganisms has decreased significantly within the last decades.
      Therefore, additional criteria for the diagnosis of IE may be helpful. It was
      hypothesized that assessment of interleukin-6 (IL-6) and interleukin-2R (IL-2R)
      may provide new diagnostic criteria for inflammation in IE. IL-6 and IL-2R serum
      concentrations, white blood cell count (WBC), and C-reactive protein (CRP) were
      measured in the blood of 47 patients with IE at the time of diagnosis and during
      treatment. WBC and CRP were elevated in patients with IE at the time of
      diagnosis. Both parameters were higher (p <0.05) in patients with positive blood
      cultures when compared with negative cultures. The differences persisted during
      the first week of treatment (p <0.01). In contrast, IL-6 and IL-2R concentrations
      were elevated (p <0.001) independently of the status of blood cultures. Serum
      concentrations of IL-6 and IL-2R decreased continuously during antibiotic
      treatment. Assessment of IL-6 and IL-2R could thus provide new diagnostic
      criteria for inflammation in IE, and these interleukins could also be suitable
      for monitoring the course of inflammation during treatment.

PMID- 12062736
TI  - Comparison of hemodynamic adaptation to orthostatic stress in patients with
      hypertrophic cardiomyopathy with or without syncope and in vasovagal syncope.
AB  - This study was designed to investigate whether, in patients with hypertrophic
      cardiomyopathy (HC), tilt-induced volume unloading triggers a peripheral reflex
      similar to that seen in patients with a history of vasovagal syncope or rather
      acts through an intrinsic cardiac mechanism secondary to diastolic dysfunction.
      Thirty-seven patients with HC (10 with and 27 without a history of syncope), 10
      patients with vasovagal syncope, and 9 controls underwent 70 degrees head-up tilt
      for 45 minutes during continuous radionuclide monitoring of left ventricular
      function. We focused on the initial 5 minutes into the tilt test, well before
      symptoms occurred, to exclude that the observed hemodynamic changes were the
      consequence rather than the cause of syncope. HC patients with previous syncope
      and vasovagal patients experienced significant hypotension after the initial 5
      minutes of tilt. Only HC patients with a history of syncope had a significant
      decrease in cardiac output, which began at the initial stage of the test.
      Systemic vascular resistance decreased in vasovagal patients, but increased in
      the HC syncopal group. Baseline peak filling rate was lower (2.4 +/- 0.5 vs 3.3
      +/- 1.1 stroke counts/s, p = 0.03) and a "pseudonormal" or a restrictive pattern
      of left ventricular filling was more frequent (70% vs 26%, p = 0.02) in HC
      patients with than without a history of syncope. Thus, significant hypotension or
      frank syncope during orthostatic stress in HC patients with a history of syncope
      is due to an early decrease in cardiac output, which occurs well before the onset
      of symptoms; such impaired hemodynamic adaptation seems to be related to
      diastolic dysfunction.

PMID- 12062737
TI  - Side effects of statins: hepatitis versus "transaminitis"-myositis versus
      "CPKitis".

PMID- 12062738
TI  - Post hoc analysis of coronary findings from the prospective randomized evaluation
      of the vascular effects of the Norvasc trial (PREVENT).

PMID- 12062739
TI  - Coincidental annual distribution of first and second acute myocardial infarction.

PMID- 12062741
TI  - Usefulness of complex atherosclerotic plaque in the ascending aorta and arch for
      predicting cardiovascular events.

PMID- 12062740
TI  - Association of mitral annular calcium on spiral computed tomography (dual-slice
      mode) with thoracic aorta calcium in patients with systemic hypertension.

PMID- 12062742
TI  - Relation of residual stenosis after angioplasty to long-term outcome of patients
      treated for in-stent restenosis with intravascular radiation therapy.

PMID- 12062743
TI  - Relation of platelet inactivation with intravenous glycoprotein IIb/IIIa
      antagonists to major bleeding (from the GOLD study).

PMID- 12062744
TI  - Effect of metoprolol on absolute myocardial blood flow in patients with heart
      failure secondary to ischemic or nonischemic cardiomyopathy.

PMID- 12062745
TI  - A novel method--the activity log index--for monitoring physical activity of
      patients with heart failure.

PMID- 12062746
TI  - Comparison of Doppler echocardiography with angiography for determining the
      severity of pulmonary regurgitation.

PMID- 12062747
TI  - Comparison of numbers of circulating blood monocytes in men grouped by body mass
      index (<25, 25 to <30, > or =30).

PMID- 12062748
TI  - Significance of shortening of the mean QRS duration of the standard
      electrocardiogram in patients developing peripheral edema.

PMID- 12062749
TI  - Heart transplantation for undiagnosed cardiac sarcoidosis.

PMID- 12062750
TI  - The heart at necropsy in massive obesity (>300 pounds or >136 kilograms).

PMID- 12062751
TI  - Reply to Dr. Dujovne's editorial.

PMID- 12062753
TI  - Estrogen receptors alpha and beta in the inner ear of the 'Turner mouse' and an
      estrogen receptor beta knockout mouse.
AB  - Estrogen receptors have earlier been shown in the normal mouse, rat and human
      inner ear. If estrogens are important in normal hearing and development of
      presbyacusis in the normal population is not known. However it is known that
      patients with Turner syndrome, where a lack of estrogens is one of the main
      characteristics, commonly develop an early presbyacusis. A 'Turner mouse' has
      been developed, as a model for the ear problems in Turner syndrome, and it shows
      otitis media and a premature aging of the hearing. Estrogen receptors exist in an
      alpha and a beta form. In this study inner ear tissue, from the Turner mouse and
      an estrogen receptor beta knockout mouse (betaERKO), was investigated regarding
      estrogen receptor alpha and beta using immunohistochemistry. Results show that
      the Turner mouse has the same pattern of inner ear labeling, both concerning the
      estrogen receptor alpha and beta, as that of a normal CBA/Ca mouse, with positive
      staining in the organ of Corti and spiral ganglion. The betaERKO mice show close
      to normal inner ear morphology and positive estrogen receptor alpha
      immunostaining at the same locations as the CBA/Ca mouse.

PMID- 12062754
TI  - PET imaging of differential cortical activation by monaural speech and nonspeech
      stimuli.
AB  - Positron emission tomography imaging was used to investigate the brain activation
      patterns of listeners presented monaurally (right ear) with speech and nonspeech
      stimuli. The major objectives were to identify regions involved with speech and
      nonspeech processing, and to develop a stimulus paradigm suitable for studies of
      cochlear-implant subjects. Scans were acquired under a silent condition and
      stimulus conditions that required listeners to press a response button to
      repeated words, sentences, time-reversed (TR) words, or TR sentences. Group
      averaged data showed activated foci in the posterior superior temporal gyrus
      (STG) bilaterally and in or near the anterior insula/frontal operculum across all
      stimulus conditions compared to silence. The anterior STG was activated
      bilaterally for speech signals, but only on the right side for TR sentences. Only
      nonspeech conditions showed frontal-lobe activation in both the left inferior
      frontal gyrus [Brodmann's area (BA) 47] and ventromedial prefrontal areas (BA
      10/11). An STG focus near the superior temporal sulcus was observed for sentence
      compared to word. The present findings show that both speech and nonspeech
      engaged a distributed network in temporal cortex for early acoustic and
      prelexical phonological analysis. Yet backward speech, though lacking semantic
      content, is perceived as speechlike by engaging prefrontal regions implicated in
      lexico-semantic processing.

PMID- 12062755
TI  - Susceptibility to the ototoxic properties of toluene is species specific.
AB  - Toluene is the most widely used industrial solvent. It has been shown to be
      ototoxic in mice and rats, and to increase permanent threshold shift in
      conjunction with exposure to noise. Chinchillas are widely used for studying
      noise effects on the cochlea. The present study was initiated to study toluene
      and noise interaction in chinchillas. Thirty-three chinchillas were exposed to a
      95 dBA 500 Hz octave band noise plus 2000 ppm toluene, 8 or 12 h per day for 10
      days. Auditory function was estimated using the auditory brainstem response (ABR)
      to tones between 500 Hz and 16 kHz. There was no effect on the ABR of toluene
      alone. Noise alone produced a threshold shift. There was no interaction of noise
      and toluene on the ear. The present study suggests that chinchillas are markedly
      less susceptible to the ototoxic effect of toluene than mice and rats. A working
      hypothesis as to the species differences was that chinchilla liver was able to
      detoxify the toluene. Hepatic microsomes from chinchillas, rats and humans were
      tested for their ability to convert toluene to the more water-soluble compound -
      benzyl alcohol. Chinchilla livers were found to contain more of the P450 enzymes
      CYP2E1 and CYP2B than rats or humans. In addition, the data show that the P450
      enzymes are more active in chinchillas than in rats and humans. In conclusion,
      the results suggest that rats and mice are a more appropriate model for human
      toluene ototoxicity. However, chinchillas may provide a valuable model for
      investigating how ototoxic agents can be detoxified to less damaging compounds.

PMID- 12062757
TI  - Contralateral inhibition in a release from forward masking.
AB  - The current study investigated contralateral inhibition involved in a release
      from forward masking. The masker and probe were 1-kHz pure tones shaped by a 20
      Hz modulation. Durations of the masker and probe were 500 ms and 50 ms (single
      cycle) respectively. A 10-ms delay between the masker and probe was added to rule
      out any confusion. A contralateral component (cue), with various spectral and
      temporal properties, could be added during the masker. The first experiment
      showed that masking release occurred more often or increased with an increasing
      number of spectral cue components. The second experiment showed that increasing
      cue duration, leaving the cue and masker offsets synchronous, increased detection
      thresholds. In the third experiment the temporal position of a short cue relative
      to the masker was varied. The lowest thresholds were obtained for 0- and 150-ms
      delays between the cue and masker offsets. Despite large individual differences,
      the obtained release from forward masking provided support for a contralateral
      inhibition process. Contralateral inhibition seemed to be dependent on the number
      of spectral cue components and on the delay between the cue onset and the masker
      offset.

PMID- 12062756
TI  - Blockade of c-Jun N-terminal kinase pathway attenuates gentamicin-induced
      cochlear and vestibular hair cell death.
AB  - The ototoxic action of aminoglycoside antibiotics leading to the loss of inner
      ear hair cells is well documented. However, the molecular mechanisms are poorly
      defined. We have previously shown that in neomycin-exposed cochlear organotypic
      cultures, the c-Jun N-terminal kinase (JNK) pathway - associated with stress,
      injury and apoptosis - is activated in hair cells. We have shown that hair cell
      death can be attenuated by CEP-1347, an inhibitor of JNK signaling (). In the
      present study, we demonstrate that gentamicin-induced ototoxicity leads to JNK
      activation and apoptosis in the inner ear hair cells in vivo. We show that
      systemic administration of CEP-1347 attenuates gentamicin-induced decrease of
      auditory sensitivity and cochlear hair cell damage. In addition, CEP-1347
      treatment reduces the extent of hair cell loss in the ampullary cristae after
      gentamicin intoxication. Particularly, the inner hair cells of the cochlea and
      type I hair cells of the vestibular organs are protected. Our previous data have
      shown that also acoustic overstimulation can cause apoptotic death of cochlear
      hair cells and that CEP-1347 can attenuate noise-induced hair cell loss. Thus,
      our results imply that activation of JNK cascade may be a common molecular
      outcome of cellular stress in the inner ear sensory epithelia and that
      attenuation of the lesion can be provided by inhibiting JNK activation.

PMID- 12062758
TI  - Reduction in the endocochlear potential caused by Cs(+) in the perilymph can be
      explained by the five-compartment model of the stria vascularis.
AB  - In an earlier publication (Takeuchi et al., Biophys. J. 79 (2000) 2572-2582), we
      proposed that K(+) channels in intermediate cells within the stria vascularis may
      play an essential role in the generation of the endocochlear potential (EP), and
      we presented an extended version of the five-compartment model of the stria
      vascularis. In search of further evidence supporting the five-compartment model,
      we studied the effects of Cs(+) added to the perilymph on guinea pig EP. Cs(+) is
      known as a competitive K(+) channel blocker. Both the scala tympani and the scala
      vestibuli of four cochlear turns were perfused at a flow rate of 10 microl/min,
      and the EP was recorded from the second cochlear turn. Cs(+) at 30 mM caused a
      biphasic change in the EP; the EP increased transiently from a control level of
      89.6 mV to 94.8 mV within 10 min, and then decreased to a steady level of 24.5 mV
      within the next 40 min. We propose that the initial transient increase in the EP
      results from Cs(+)-mediated blockade of K(+) conductance in the basolateral
      membrane of hair cells, and that the subsequent EP decrease is due to effects of
      Cs(+) on the stria vascularis. We believe that Cs(+) in the perilymph is able to
      access the stria vascularis by being taken up by fibrocytes in the spiral
      ligament and then being transported to intermediate cells because it is known
      that Cs(+) is taken up via Na(+),K(+)-ATPase and that gap junctions connect
      fibrocytes in the spiral ligament to basal cells and basal cells to intermediate
      cells. To clarify the effect of intracellular Cs(+) on the electrophysiological
      properties of intermediate cells, these cells were dissociated from guinea pigs
      and studied by the whole-cell patch-clamp method. Intracellular Cs(+) depolarized
      intermediate cells in a dose-dependent manner. In addition, efflux of Cs(+) from
      the intermediate cell was much less than the efflux of K(+). Thus, Cs(+) may
      accumulate in the intermediate cell, which depolarizes the cell, which in turn
      decreases the EP. We conclude that the five-compartment model of the stria
      vascularis can explain the EP decrease caused by Cs(+) in the perilymph.

PMID- 12062759
TI  - Involvement of apoptosis in progression of cochlear lesion following exposure to
      intense noise.
AB  - It has been known for some time that noise-induced outer hair cell (OHC) death in
      the cochlea continues well after the termination of a noise exposure. However,
      the underlying mechanisms leading to the expansion of a cochlear lesion are not
      fully understood. Here we report involvement of the apoptotic pathway in the
      progression of OHC death in the chinchilla cochlea following exposure to a 4 kHz
      narrow band noise at 110 dB SPL for 1 h. Morphological examination of OHC nuclei
      revealed nuclear condensation and fragmentation, typical morphological features
      of apoptosis. OHC apoptosis developed asymmetrically toward the apical and basal
      parts of the cochleas following the noise exposure. Two days after the noise
      exposure, there was still active OHC pathology with condensed and fragmented
      nuclei in the basal part of the cochleas. Detection of caspase-3 activation, an
      intracellular marker for apoptosis, showed a spatial agreement between the
      apoptotic nuclei and activated caspase-3. These results clearly implicate the
      apoptotic pathway in the post-exposure progression of OHC demise.

PMID- 12062760
TI  - Long-term observations on the reversibility of cochlear dysfunction after
      transient ischemia.
AB  - To examine the reversibility of functional damage to the cochlea after transient
      ischemia, cochlear ischemia of 0-60 min was induced in 34 albino guinea pigs.
      Thresholds of auditory brainstem response (ABR) were then followed for 5 days
      after ischemia. Although the ABR threshold returned to almost the pre-ischemic
      value after 15 min ischemia, ischemia of 30 and 60 min duration induced
      irreversible dysfunction. Aminoguanidine, an inducible NO synthase (iNOS)
      inhibitor, significantly ameliorated the post-ischemic cochlear dysfunction
      induced by 60 min ischemia. Morphological findings of the hair cells were
      consistent with these functional results. These results indicate that ischemia of
      30 min or longer induces irreversible damage to the cochlea and that iNOS plays
      injury-producing roles in this type of injury.

PMID- 12062761
TI  - Breed differences in cochlear integrity in adult, commercially raised chickens.
AB  - Two types of chickens are commercially available. Broiler birds are bred to
      develop quickly for meat production, while egg layers are bred to attain a
      smaller adult size. Because we have observed breed differences in the response of
      central auditory neurons to cochlear ablation in adult birds [Edmonds et al.
      (1999) Hear. Res. 127, 62-76], we examined cochleae from the two breeds for
      differences in integrity. We evaluated cochlear hair cell structure using
      scanning electron microscopy and cochlear hair cell function using distortion
      product otoacoustic emissions (DPOAEs) and the auditory brainstem response. We
      observed striking breed differences in cochlear integrity in adult but not
      hatchling birds. In adult broiler birds, all cochleae showed damage, encompassing
      at least the basal 29% of the cochlea. In 15 of 18 broiler ears, damage was
      observed throughout the basal 60% of the cochlea. In contrast, cochleae from egg
      layer adults were largely normal. Two thirds of egg layer ears showed no
      anatomical abnormalities, while in the remainder cochlear damage was seen within
      the basal 48% of the cochlea. DPOAEs recorded from egg layer birds showed loss of
      high frequency emissions in every ear for which the cochlea displayed anatomical
      damage. Average sound pressure levels in both commercial facilities were 90 dB,
      suggesting these two breeds may exhibit differential susceptibility to noise
      damage.

PMID- 12062762
TI  - Models of otolithic membrane-hair cell bundle interaction.
AB  - Transformation of the mechanical input in the chain: acceleration of otolithic
      membrane (OM)-displacement of the OM gel layer-deflection of hair cell bundle
      (HCB)-formation of the temporal pattern of polarization was studied using
      simplified analytical models of these stages of conversion of mechanical stimulus
      into the HCB electrical response. The dynamic behavior of an OM was modeled by a
      homogeneous viscoelastic (Kelvin-Voight body) model of the OM. Two alternative
      models of an 'HCB-surrounding gel' interaction corresponding to different types
      of the HCB were considered: (1) a model of stereocilia tip-link deformation in
      the case when the HCBs passively follow the gel deformation and (2) a model in
      which the tip-link dynamics is determined by an 'HCB-viscous fluid' interaction.
      It was shown that in the first model the 'HCB-OM gel' system functions as an
      accelerometer while in the second model it measures the time derivative of
      external acceleration. A simplified model of the temporal formation of cell
      depolarization is proposed and analyzed. Results of the modeling suggest that
      formation of a temporal response of the HCB to external acceleration occurs
      mainly due to two mutually correlated factors: the spatial dependence of gel
      displacement on the distance from a macular plane and the spatial distribution of
      stereocilia heights in the HCB.

PMID- 12062763
TI  - Differential ototoxicities induced by lead acetate and tetraethyl lead.
AB  - Lead poisoning disrupts many biological structures and functions, including those
      of the auditory system. This study examined the ototoxic effects of lead acetate
      (LA) and tetraethyl lead (TEL) of equal lead content on cochlear function and the
      ability of alpha-phenyl-tert-butyl-nitrone (PBN) to attenuate such effects.
      Baseline 1.0 microV cochlear microphonic (CM) and compound action potential (CAP)
      responses were recorded and animals administered either PBN (100 mg/kg, i.p.) or
      an equal volume of 0.9% saline, followed by an i.p. injection of LA (50 mg/kg) in
      an ethanol vehicle, TEL (42.7 mg/kg) in a corn oil vehicle, corn oil or ethanol
      vehicle alone. Two hours after administration, post-exposure CM and CAP responses
      were recorded. CAP threshold shifts in the saline-LA group were elevated by 5-10
      dB at mid to high frequencies relative to controls (20-24 kHz, P<0.05). Mean CAP
      threshold shifts in the saline-TEL were significantly greater than those of both
      control groups at all tested frequencies except 2 kHz (P<0.001). However,
      threshold shifts in the group receiving PBN prior to TEL were significantly
      smaller than shifts in the group receiving saline prior to TEL (P<0.01). These
      data suggest that TEL is more ototoxic than is LA and that free radicals
      partially mediate TEL-induced CAP disruption.

PMID- 12062764
TI  - The effect of sound duration on rate-amplitude functions of inferior collicular
      neurons in the big brown bat, Eptesicus fuscus.
AB  - During echolocation, the amplitude and duration of echo pulses of the big brown
      bat, Eptesicus fuscus, covary throughout the entire course of hunting. The
      purpose of this study was to examine if variation in sound duration might affect
      the amplitude selectivity of inferior collicular (IC) neurons of this bat species
      under free-field stimulation conditions. A family of rate-amplitude functions of
      each IC neuron was obtained with different sound durations. The effect of sound
      duration on the neuron's amplitude selectivity was then studied by examining the
      type, best amplitude, dynamic range and slope of each rate-amplitude function.
      The rate-amplitude functions of 83 IC neurons determined with different sound
      durations were either monotonic, saturated or non-monotonic. Neurons with
      monotonic rate-amplitude functions had the highest best amplitude, largest
      dynamic range but smallest slope. Neurons with non-monotonic rate-amplitude
      functions had the lowest best amplitude, smallest dynamic range but largest
      slope. The best amplitude, dynamic range and slope of neurons with saturated rate
      amplitude functions were intermediate between these two types. Rate-amplitude
      functions of one group (47, 57%) of IC neurons changed from one type to another
      with sound duration and one-third of these neurons were tuned to sound duration.
      As a result, the best amplitude, dynamic range, and slope also varied with sound
      duration. However, rate-amplitude functions of the other group (36, 43%) of IC
      neurons were hardly affected by sound duration and two-thirds of these neurons
      were tuned to sound duration. Biological relevance of these findings in relation
      to bat echolocation is discussed.

PMID- 12062765
TI  - Click-evoked otoacoustic emissions recorded from untreated congenital hypothyroid
      newborns.
AB  - Thyroid hormone plays an important role in hearing development. Both a genetic or
      non-genetic hypothyroidism is often associated with congenital hearing loss. The
      exact incidence of hearing impairment in untreated congenital hypothyroid (CH)
      patients is unknown. This paper will present the results of measuring of the
      transient-evoked otoacoustic emissions (TEOAE) in a population of 29 newborns,
      who tested positive on a screening test for hypothyroidism (CH group) and in 68
      well babies (control group) randomly chosen from all the newborns, classified as
      PASS, included in the Hearing Screening Program of the San Raffaele Hospital in
      Milan. TEOAE were recorded in all newborns within 1 month after birth and before
      beginning L-thyroxine treatment with conventional commercial instrumentation.
      Both temporal and time-frequency analyses of the emitted responses were conducted
      by means of a wavelet transform. The comparison of the characteristics of the
      temporal and frequency content of the responses of the two groups (CH and
      control) showed no statistically significant difference. No correlation was found
      between outer hair cell dysfunction and hypothyroidism.

PMID- 12062766
TI  - Amplitude--intensity functions for auditory middle latency responses in hearing
      impaired subjects.
AB  - Results from animal studies show that hearing loss can result in increased neural
      responsiveness within the central auditory system. This study employed auditory
      middle latency evoked responses to compare central auditory responsiveness in
      human males with and without hearing loss. Measurements of auditory middle
      latency responses (MLRs) recorded from 14 normal hearing males were compared with
      MLR measures from 14 males with high-frequency, sensorineural hearing loss.
      Sixteen toneburst stimuli (four frequencies x four intensities) were used. Slopes
      of the amplitude-intensity functions for the several components of the MLR were
      obtained for each subject at frequencies below, near, and above the audiometric
      edge. Analysis of variance (ANOVA) revealed a significant group effect for MLR
      component Pa-Na, with less steep slopes at all frequencies for the hearing
      impaired group. The ANOVA also showed a trend towards a significant group effect
      for Pb-Nb. Two-sample t-tests performed for Pb-Nb for each of the four tonebursts
      showed a frequency-specific effect. For Pb-Nb there was a statistically greater
      mean slope for the hearing-impaired group at the toneburst frequency associated
      with the audiometric edge.

PMID- 12062767
TI  - Late-onset hearing loss in a mouse model of DFN3 non-syndromic deafness:
      morphologic and immunohistochemical analyses.
AB  - Recently, we reported that homozygous males and females of a mouse model of DFN3
      non-syndromic deafness generated by the deletion of Brn-4 transcription factor
      showed profound deafness due to severe alterations in the cochlear spiral
      ligament fibrocytes from the age of 11 weeks, whereas no hearing loss was
      recognized in young female heterozygotes. It is known that a part of obligate
      female carriers of DFN3 showed progressive hearing loss. In the present study, we
      examined the late-onset effect of Brn-4 deficiency on the hearing organ of the
      mouse. About one third of heterozygous female mice revealed late-onset profound
      deafness at the age of 1 year. Furthermore, in these deafened heterozygotes,
      characteristic abnormalities in Reissner's membrane attachment and type II
      fibrocytes in the suprastrial zone became evident under light microscope, similar
      to homozygous female mice. A significant reduction in the immunoreactivity of
      connexin 26 (Cx26), connexin 31 (Cx31), Na,K-ATPase and Na-K-Cl cotransporter in
      the spiral ligament fibrocytes was observed in aged heterozygotes showing late
      onset profound deafness. The late-onset phenotype observed in heterozygous mutant
      mice, being consistent with the progressive deafness observed in human female
      heterozygotes, may be explained by alterations of the ion transport systems in
      the spiral ligament fibrocytes.

PMID- 12062768
TI  - Chronic placental insufficiency has long-term effects on auditory function in the
      guinea pig.
AB  - Very low birth weight and growth-restricted infants have an increased risk of
      auditory impairments. It is uncertain whether these impairments are related to
      adverse pre-, peri- or postnatal events. We aimed to determine whether a period
      of chronic placental insufficiency (CPI) in the guinea pig results in long-term
      alterations to auditory function. Near mid-gestation, CPI was induced via
      unilateral ligation of the uterine artery. At 8 weeks of age, auditory brainstem
      responses (ABRs) were recorded in response to unilateral acoustic stimulation in
      prenatally-compromised (PC, n=8) and control animals (n=8). Stimuli consisted of
      100 micros clicks, presented at 33 pulses per second (pps) and tone pip stimuli
      at frequencies of 2, 4, 8, 16 and 32 kHz. To examine temporal response
      properties, click stimuli were also presented at rates of 66, 132 and 200 pps.
      Normal ABR waveforms were elicited by both click and tone pip stimuli in all
      animals. Moreover, there was no difference between control and PC animals in
      stimulus detection thresholds across the frequencies examined. Using high rate
      click stimuli, PC animals demonstrated a significant increase in both the latency
      of wave III (normalised to 33 pps) and the wave I-III inter-peak interval
      compared to the controls. We hypothesise that these functional changes reflect
      alterations in myelination of the auditory brainstem and/or changes in synaptic
      efficacy. The results suggest subtle deficits in neural conduction in the PC
      guinea pig at maturity, and may have implications for speech perception abilities
      of low birth weight or prenatally affected infants.

PMID- 12062769
TI  - The presence and arrangement of type II collagen in the basilar membrane.
AB  - Previous studies demonstrating the presence of collagen II in the basilar
      membrane have used a biochemical approach or have used immunohistochemistry at
      the light microscopic level. In this investigation both the presence and
      arrangement of collagen II were demonstrated at the ultrastructural level using
      pre- and post-embedding immunoelectron microscopy. Labeling was dependent on the
      development of protocols to expose epitopes while maintaining identifiable
      ultrastructure. Both positive and negative controls indicate that the labeling
      was specific for collagen II. Collagen II was detected in the fibrous sheet of
      the pars tecta and in the two fibrous layers of the pars pectinata. It was
      detected in situ and on isolated individual 10-12 nm fibrils. The presence of
      collagen II in all the fibrous layers of the basilar membrane places constraints
      on the biomechanical properties of this important structure.

PMID- 12062770
TI  - Immunolabeling type II collagen in the basilar membrane, a pre-embedding
      approach.
AB  - This paper describes the development of a protocol that can be used to detect
      collagen II in the healthy adult basilar membrane (BM) at the electron
      microscopic level. This protocol required aggressive epitope exposure techniques
      to break the crosslinks that bind the collagen molecules tightly into fibrils and
      to remove a dense mat of ground substance that surrounds the fibrils. On the
      other hand, the steps had to be carefully controlled to preserve BM
      ultrastructure and the collagen II epitopes that are typically labile. These
      requirements were satisfied by introducing a targeted crosslink breakage method
      and by regulating the duration of epitope exposure based on changes in tissue
      appearance observed with differential interference contrast microscopy. High
      levels of immunolabeling were achieved by substituting tissue preservation
      techniques for most or all of fixation; this was important because fixation
      reduces antigenicity directly and impedes epitope exposure. When these techniques
      were combined with more traditional trypsin and pepsin treatments, the result was
      dense immunolabeling and preservation of ultrastructure that allowed accurate
      localization of the immunolabeling. This pre-embedding immunoelectron microscopic
      method is the first to be carried out on the BM and may be adaptable to future
      studies of the BM as well as other tissues with similar molecular composition.

PMID- 12062771
TI  - Human frequency-following responses: representation of steady-state synthetic
      vowels.
AB  - Auditory nerve single-unit population studies have demonstrated that phase
      locking plays a dominant role in the neural encoding of the spectrum of speech
      sounds. Given this, it was reasoned that the phase-locked neural activity
      underlying the scalp-recorded human frequency-following response (FFR) might
      preserve information about certain acoustic features of speech sounds. It was
      recently reported (Ananthanarayan, A.K., 1999. J. Audiol. Neurootol. 4, 95-103)
      that the FFR spectrum to simple two-tone approximations of several English back
      vowels does indeed contain peaks corresponding to the first and second formant
      frequencies. In this investigation FFRs to the more complex steady-state
      synthetic English back vowels (/u/, /)/, and /a/) were evaluated. FFRs were
      obtained from 10 normal-hearing human adults at 85, 75, 65, and 55 dB normal
      hearing level (nHL). Spectrum analyses of the FFRs revealed distinct peaks at
      harmonics adjacent to the first and the second formants across all levels
      suggesting that phase-locked activity among two distinct populations of neurons
      is indeed preserved in the FFR. For each vowel the spectral peaks at first
      formant harmonics dominated the spectrum at high stimulus levels suggesting
      formant capture. The observation of less robust peaks for harmonics between the
      formants may very well suggest selective suppression to enhance spectral peaks at
      the formant frequencies. These results suggest that the scalp-recorded FFR may
      provide for a non-invasive analytic window to evaluate neural encoding of speech
      sounds in the brainstem of normal-hearing individuals and how this encoding may
      be degraded subsequent to cochlear hearing impairment.

PMID- 12062772
TI  - Comparison between local field potentials and unit cluster activity in primary
      auditory cortex and anterior auditory field in the cat.
AB  - Multi-unit (MU) activity and local field potentials (LFP) were simultaneously
      recorded from 161 sites in the middle cortical layers of the primary auditory
      cortex (AI) and the anterior auditory field (AAF) in 51 cats. Responses were
      obtained for frequencies between 625 Hz and 40 kHz, at intensities from 75 dB SPL
      to threshold. We compared the response properties of MU activity and LFP
      triggers, in terms of characteristic frequency (CF), threshold at CF, minimum
      latency and frequency tuning-curve bandwidth 20 dB above threshold. On average,
      thresholds at CF were significantly lower for LFP events than those for MU spikes
      (4.6 dB for AI, and 3 dB for AAF). Minimum latencies were significantly shorter
      for LFP events than for MU spikes (1.5 ms in AI, and 1.7 ms in AAF). Frequency
      tuning curves were significantly broader for LFP events than those for MU spikes
      (1.0 octave in AI, and 1.3 octaves in AAF). In contrast, the CF was not
      significantly different between LFP events and MU spikes. The LFP results
      indicate that cortical neurons receive convergent sub-cortical inputs from a
      broad frequency range. The sharper tuning curves for MU activity compared to
      those of LFP events are likely the result of intracortical inhibitory processes.

PMID- 12062773
TI  - Non-osseous sound transmission to the inner ear.

PMID- 12062775
TI  - Correlates of received and expressed violence persistence following substance
      abuse treatment.
AB  - This study examined different types of violence (i.e. 'expressed' towards others
      and 'received' from others) across different relationship types (i.e. 'partners'
      and 'non-partners') among men and women in substance abuse treatment, and during
      a 2-year follow-up period. For received violence, participants were divided into
      three groups: no-violence before or after treatment, violence before treatment
      only, and violence both before and after treatment. Similarly, participants also
      were divided into three groups based on expressed violence: no-violence before or
      after treatment, violence before treatment only, and violence both before and
      after treatment. Both expressed and received violence (either before or after
      treatment) was associated with younger age. Unique demographic markers of
      received violence included being female, reporting less income and greater
      unemployment. For both received and expressed violence, several problem severity
      indicators (e.g. drug consequences, psychological distress) and psychosocial
      relapse risk indicators (e.g. resource needs, substance-using leisure activities)
      differentiated those who reported violence (either before or after treatment) and
      those who did not report violence. In addition, received violence was related to
      greater exposure to substances whereas expressed violence was related to greater
      cocaine use and craving. Continued received and expressed violence post-treatment
      was related to substance use during the follow-up, recruitment from inpatient
      treatment, and baseline psychological distress (expressed violence only). The
      results are consistent with contemporary models of violence specifying the impact
      of substance use, social/contextual and individual difference factors, and
      highlight risk factors that could be targeted during treatment to potentially
      reduce post-treatment substance use and violence.

PMID- 12062776
TI  - Dialectical behavior therapy versus comprehensive validation therapy plus 12-step
      for the treatment of opioid dependent women meeting criteria for borderline
      personality disorder.
AB  - We conducted a randomized controlled trial to evaluate whether dialectical
      behavior therapy (DBT), a treatment that synthesizes behavioral change with
      radical acceptance strategies, would be more effective for heroin-dependent women
      with borderline personality disorder (N = 23) than Comprehensive Validation
      Therapy with 12-Step (CVT + 12S), a manualized approach that provided the major
      acceptance-based strategies used in DBT in combination with participation in 12
      Step programs. In addition to psychosocial treatment, subjects also received
      concurrent opiate agonist therapy with adequate doses of LAAM (thrice weekly;
      modal dose 90/90/130 mg). Treatment lasted for 12 months. Drug use outcomes were
      measured via thrice-weekly urinalyses and self-report. Three major findings
      emerged. First, results of urinalyses indicated that both treatment conditions
      were effective in reducing opiate use relative to baseline. At 16 months post
      randomization (4 months post-treatment), all participants had a low proportion of
      opiate-positive urinalyses (27% in DBT; 33% in CVT + 12S). With regard to between
      condition differences, participants assigned to DBT maintained reductions in mean
      opiate use through 12 months of active treatment while those assigned to CVT +
      12S significantly increased opiate use during the last 4 months of treatment.
      Second, CVT + 12S retained all 12 participants for the entire year of treatment,
      compared to a 64% retention rate in DBT. Third, at both post-treatment and at the
      16-month follow-up assessment, subjects in both treatment conditions showed
      significant overall reductions in level of psychopathology relative to baseline.
      A noteworthy secondary finding was that DBT participants were significantly more
      accurate in their self-report of opiate use than were those assigned to CVT +
      12S.

PMID- 12062777
TI  - Substance use among adolescents in Taiwan: associated personality traits,
      incompetence, and behavioral/emotional problems.
AB  - BACKGROUND: Despite that adolescent substance use is increasingly prevalent
      throughout the world and leads to increased risk of progression to illicit drug
      use, few studies have examined in detail individual features that are associated
      with such use. We aimed to examine personality traits, incompetence, and
      behavioral/emotional problems in relation to adolescent substance use and
      possible interactions between these factors. METHODS: Junior high school
      adolescents (N = 905) randomly selected from Taipei in 1996 completed a
      questionnaire consisting of substance use experience, the Junior Eysenck
      Personality Questionnaire (JEPQ), and the Tridimensional Personality
      Questionnaire (TPQ). Students' parents (N = 854) were asked to complete the Child
      Behavior Checklist. Logistic regression was used to assess the relationship
      between substance use and personality traits or behavioral problems. RESULTS: The
      most commonly used substance was liquid substance (alcohol and refreshing
      beverage), followed by tobacco and betel nut with an age-related trend in boys.
      Associated factors of substance use included higher Extroversion and lower Lie
      Scale (as measured in the JEPQ), higher Novelty Seeking (as measured in the TPQ),
      poorer School Competence, and more Delinquent Behavior, Aggressive Behavior, and
      Somatic Complaints. The associations remained unchanged with potential
      confounders controlled for. CONCLUSIONS: Adolescents who use substance have
      specific individual features that are readily assessable by existing instruments.
      This bears important implications for the early intervention of substance abuse
      in adolescents.

PMID- 12062778
TI  - Cognitive impairment in methadone maintenance patients.
AB  - Few well-controlled studies have examined psychomotor and cognitive performance
      in methadone maintenance patients (MMP). In the present study, performance of 18
      opioid-dependent MMP was evaluated relative to that of 21 control participants
      without substance abuse histories. The MMP and control groups were balanced with
      respect to gender, race, age, years of education, current employment status,
      current reading level, and estimated IQ score. Recent drug abstinence was
      verified by urine testing. Participants with a urine screen positive for
      benzodiazepines or a breathalyzer test positive for alcohol prior to performance
      testing were excluded. To avoid testing under conditions of acute heroin or
      cocaine intoxication, but without testing under conditions of acute withdrawal,
      participants with current use of heroin or cocaine were only required to abstain
      for 24 h prior to performance testing. MMP exhibited impairment relative to
      controls in psychomotor speed (digit symbol substitution and trail-making tests),
      working memory (two-back task), decision making (gambling task), and metamemory
      (confidence ratings on a recognition memory test); results also suggested
      possible impairment in inhibitory mechanisms (Stroop color-word paradigm). MMP
      did not exhibit impairment in time estimation, conceptual flexibility or long
      term memory. The wide range of impaired functions is striking, and may have
      important implications for daily functioning in MMP. Further research is
      necessary to determine the clinical significance of the impairments in laboratory
      based tests for daily performance in the natural environment, as well as to
      differentiate impairments due to acute methadone dosing, chronic methadone
      maintenance, chronic poly-drug abuse, and other factors.

PMID- 12062779
TI  - The effectiveness of drug abuse treatment: a meta-analysis of comparison group
      studies.
AB  - A meta-analysis was conducted on 78 studies of drug treatment conducted between
      1965 and 1996. Each study compared outcomes among clients who received drug
      treatment with outcomes among clients who received either minimal treatment or no
      treatment. Five methodological variables were significant predictors of effect
      size. Larger effect sizes were associated with studies with the following
      characteristics: smaller numbers of dependent variables, significant differences
      between groups at admission, low levels of attrition in the treatment group, a
      passive comparison group (no treatment, minimal treatment) as opposed to an
      active comparison group (standard treatment), and drug use determined by a drug
      test. Controlling for these methodological variables, further analyses indicated
      that drug abuse treatment has both a statistically significant and a clinically
      meaningful effect in reducing drug use and crime, and that these effects are
      unlikely to be due to publication bias. For substance abuse outcomes, larger
      effect sizes tended to be found in studies in which treatment implementation was
      rated high, the degree of theoretical development of the treatment was rated low,
      or researcher allegiance to the treatment was rated as favorable. For crime
      outcomes, only the average age of study participants was a significant predictor
      of effect size, with treatment reducing crime to a greater degree among studies
      with samples consisting of younger adults as opposed to older adults. Treatment
      modality and other variables were not related to effect sizes for either drug use
      or crime outcomes

PMID- 12062780
TI  - Decreased activity of brain phospholipid metabolic enzymes in human users of
      cocaine and methamphetamine.
AB  - Phospholipids are essential components of cell membranes which may also function
      to mediate some of the behavioural effects of dopamine receptor stimulation
      caused by psychostimulant drugs. Neuroimaging and pharmacological data suggest
      that abnormal brain metabolism of phospholipids might explain some of the
      consequences of chronic exposure to drugs of abuse including drug craving. We
      previously reported decreased activity of calcium-stimulated phospholipase A(2)
      (Ca-PLA(2)) in autopsied putamen of human cocaine users. To establish the
      specificity of this change in phospholipid metabolism and whether decreased Ca
      PLA(2) might be a general feature of all abused drugs which enhance dopaminergic
      neurotransmission, we measured activity of 11 major phospholipid metabolic
      enzymes in dopamine-rich (putamen) and poor brain areas of chronic users of
      cocaine and of methamphetamine. Enzyme changes were restricted to the putamen
      which showed decreased (-21%, as compared with the control subjects) Ca-PLA(2)
      activity in users of methamphetamine and reduced (-31%) activity of
      phosphocholine cytidylyltransferase (PCCT), the rate-limiting enzyme of
      phosphatidylcholine synthesis, in the cocaine users. We suggest that chronic
      exposure to psychostimulant drugs might cause a compensatory downregulation of Ca
      PLA(2) in dopamine-rich brain areas due to excessive dopamine-related stimulation
      of the enzyme. Decreased striatal Ca-PLA(2) and/or PCCT activity in cocaine users
      might also help to explain why CDP choline, which enhances phospholipid
      synthesis, reduces craving in some users of the drug cocaine.

PMID- 12062781
TI  - Cocaine use in New South Wales, Australia, 1996-2000: 5 year monitoring of trends
      in price, purity, availability and use from the illicit drug reporting system.
AB  - This paper describes trends in the price, purity, availability and use of cocaine
      in Sydney, Australia monitored by the Illicit Drug Reporting System (IDRS)
      between 1996 and 2000. The IDRS monitors illicit drug trends by means of
      triangulation of data from interviews with injecting drug users (IDU), reports of
      key informants, and analysis of indicator data. The price of a 'cap' of cocaine
      fell from 80 Australian dollars in 1997 to 50 Australian dollars in 1998, and
      remained at the lower price in subsequent years. Cocaine purity was high in all
      years (range 50-64%), and was highest in the 1997-1998 period. The availability
      of cocaine and its use by IDU increased substantially, 1997 and 1998, and
      remained high in subsequent years. The median number of cocaine use days also
      increased substantially between 1997 (4 days) and 1998 (25 days), and remained at
      higher levels than prior to 1998 in subsequent years. Cocaine use was primarily
      of powder, by injection, and strongly associated with existing heroin injectors.
      The availability and use of crack remained rare in Sydney. Use of cocaine among
      IDU was associated with more frequent injections, more injection-related health
      problems, higher levels of needle sharing, and higher levels of criminality. It
      is concluded that the use and availability of cocaine in Sydney increased
      substantially between 1997 and 1998, and has remained entrenched in the Sydney
      illicit drug market. The regular and formal monitoring of illicit drug trends
      enabled substantial changes in the cocaine market in Sydney to be detected, and
      the information to be fed back to the health and law enforcement sectors.

PMID- 12062782
TI  - GHB use among Australians: characteristics, use patterns and associated harm.
AB  - The aim of this study was to examine the characteristics of gamma-hydroxybutyrate
      (GHB) users, their GHB and other drug use patterns, and the harms associated with
      GHB use. Seventy-six GHB users were recruited and administered a structured
      interview on GHB use and related harms. GHB users appeared to be a stable, highly
      educated and well-functioning group. They had had extensive experience with a
      range of drugs, and GHB was typically used in conjunction with other drugs.
      Despite the fact that most GHB users had not had a long or extensive experience
      with GHB use, the proportion reporting significant negative side effects when
      using GHB was high (99% reported at least one), and the mean number of side
      effects ever experienced was 6.5. Notably, half (52%) reported becoming
      unconscious, 53% reported vomiting, 58% reported profuse sweating, and 8%
      reported having a fit or seizure. The high rate of problems reported by a group
      with limited use of this drug suggests that in a context of polydrug use, GHB use
      is associated with significant risks to users.

PMID- 12062783
TI  - Sex differences in gamma-glutamyltransferase in people aged 40-42 years in two
      Norwegian counties.
AB  - Gamma-glutamyltransferase (GGT) is widely used as a marker of alcohol intake,
      although it is documented that other factors are also associated with serum
      levels of GGT. The total population of men and women aged 40-42 years in two
      Norwegian counties was invited to participate in a health survey program. GGT was
      measured in 8116 men and 8689 women--67 % of the eligible population. In sex
      specific multiple regression analyses, GGT showed a positive association with
      body mass index (BMI), cholesterol, ln triglycerides, systolic blood pressure,
      and number of drinks per 2 weeks for both men and women. Glucose and 'years of
      smoking' were significant in women only. Cups of boiled coffee per day and
      physical activity in spare time were inversely associated with GGT level for both
      men and women. A significant positive interaction between alcohol intake and BMI
      was observed for men but not for women. The use of GGT as a marker of alcohol
      consumption in middle-aged persons should take into account sex, BMI and drinking
      of boiled coffee.

PMID- 12062784
TI  - Using ambulance attendances to recruit people who have experienced non-fatal
      heroin overdose.
AB  - AIMS: To trial two novel methods of recruiting people who experience non-fatal
      heroin overdose through the ambulance service. SETTING: Melbourne and Sydney,
      Australia. METHODS: In Melbourne potential participants were given numbered
      contact cards by ambulance paramedics after revival, while in Sydney potential
      participants were approached after revival by a researcher who travelled with
      ambulance paramedics to the overdose scene. RESULTS: In Melbourne 281 cards were
      distributed during the period 1 June 1998-31 December 1998 and a subsequent
      contact rate of 24% was achieved with 14% attending a subsequent interview. In
      Sydney there were 170 initial contacts of which 139 (82%) answered a series of
      questions asked at the scene (the remainder either ineligible or incapable of
      answering questions) with 48 (35%) also attending for follow-up interviews.
      CONCLUSIONS: Recruitment through contact with ambulance services is a novel
      method of recruiting heroin users for research into non-fatal heroin overdose
      with advantages over other methods of sampling for research on non-fatal heroin
      overdose.

PMID- 12062785
TI  - Neuropsychological deficits and opiate abuse.
AB  - Cognitive functioning was examined in people with a current or past history of
      opiate abuse using a range of neuropsychological tests. Sixty percent of those
      currently abusing opiates showed impairments of at least two standard deviations
      from the published norms on two or more neuropsychological tests, a significantly
      higher incidence than found in matched controls with no history of drug abuse.
      The drug free group of recovering addicts fell between the other groups without
      significant differences. It was concluded that the risk of neuropsychological
      impairment is greater in opiate abusers, and that recovery may occur during
      abstinence.

PMID- 12062786
TI  - Avian influenza and human health.
AB  - Natural infections with influenza A viruses have been reported in a variety of
      animal species including humans, pigs, horses, sea mammals, mustelids and birds.
      Occasionally devastating pandemics occur in humans. Although viruses of
      relatively few HA and NA subtype combinations have been isolated from mammalian
      species, all 15 HA subtypes and all 9 NA subtypes, in most combinations, have
      been isolated from birds. In the 20th century the sudden emergence of
      antigenically different strains transmissible in humans, termed antigenic shift,
      has occurred on four occasions, 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977
      (H1N1), each time resulting in a pandemic. Genetic analysis of the isolates
      demonstrated that 'new' strains most certainly emerged after reassortment of
      genes of viruses of avian and human origin in a permissive host. The leading
      theory is that the pig represents the 'mixing vessel' where this genetic
      reassortment may occur. In 1996, an H7N7 influenza virus of avian origin was
      isolated from a woman with a self-limiting conjunctivitis. During 1997 in Hong
      Kong, an H5N1 avian influenza virus was recognised as the cause of death of 6 of
      18 infected patients. Genetic analysis revealed these human isolates of H5N1
      subtype to be indistinguishable from a highly pathogenic avian influenza virus
      that was endemic in the local poultry population. More recently, in March 1999,
      two independent isolations of influenza virus subtype H9N2 were made from girls
      aged one to four who recovered from flu-like illnesses in Hong Kong.
      Subsequently, five isolations of H9N2 virus from humans on mainland China in
      August 1998 were reported. H9N2 viruses were known to be widespread in poultry in
      China and other Asian countries. In all these cases there was no evidence of
      human to human spread except with the H5N1 infections where there was evidence of
      very limited spread. This is in keeping with the finding that all these viruses
      possessed all eight genes of avian origin. It may well be that infection of
      humans with avian influenza viruses occurs much more frequently than originally
      assumed, but due to their limited effect go unrecognised. For the human
      population as a whole the main danger of direct infection with avian influenza
      viruses appears to be if people infected with an 'avian' virus are infected
      simultaneously with a 'human' influenza virus. In such circumstances reassortment
      could occur with the potential emergence of a virus fully capable of spread in
      the human population, but with antigenic characteristics for which the human
      population was immunologically naive. Presumably this represents a very rare
      coincidence, but one which could result in a true influenza pandemic.

PMID- 12062787
TI  - The 1999-2000 avian influenza (H7N1) epidemic in Italy: veterinary and human
      health implications.
AB  - From the end of March to the beginning of December 1999, 199 outbreaks of low
      pathogenicity avian influenza (LPAI) were diagnosed in the Veneto and Lombardia
      regions, which are located in the northern part of Italy. The virus responsible
      for the epidemic was characterized as a type A influenza virus of the H7N1
      subtype of low pathogenicity. On the 17th of December, highly pathogenic avian
      influenza (HPAI) was diagnosed in a meat turkey flock in which 100% mortality was
      observed in 72 h. The infection spread to the industrial poultry population of
      northern Italy including chickens, guinea-fowl, quail, pheasants, ducks and
      ostriches for a total of 413 outbreaks. Over 13 million birds were affected by
      the epidemic, which caused dramatic economic losses to the Italian poultry
      industry with severe social and economic implications. The possibility of H7
      virus transmission to humans in close contact with the outbreaks was evaluated
      through a serological survey. Seven hundred and fifty nine sera were collected
      and tested for the detection of anti-H7 antibodies by means of the micro
      neutralization (MN) and single radial haemolysis (SRH) tests. All samples
      resulted negative. A limited number of clinical samples were also collected for
      attempted virus isolation with negative results. Current European legislation
      considers LPAI and HPAI as two completely distinct diseases, not contemplating
      any compulsory eradication policy for LPAI and requiring eradication for HPAI.
      Evidence collected during the Italian 1999-2000 epidemic indicates that LPAI due
      to viruses of the H7 subtype may mutate to HPAI, and, therefore, LPAI caused by
      viruses of the H5 or H7 subtypes must be controlled to avoid the emergence of
      HPAI. A reconsideration of the current definition of avian influenza adopted by
      the EU, could possibly be an aid to avoiding devastating epidemics for the
      poultry industry in Member States.

PMID- 12062788
TI  - The burden of Leishmania chagasi infection during an urban outbreak of visceral
      leishmaniasis in Brazil.
AB  - First noted in the city of Teresina in 1981, the last decades have witnessed a
      remarkable increase in urban transmission of American visceral leishmaniasis (VL)
      in many Brazilian cities. Teresina, the site of this study, has faced two large
      outbreaks of VL. The first occurred from 1981-1985 when almost 1000 new cases
      were reported. The second started in the 1990s, and between 1993 and 1996 more
      than 1200 new cases were detected. This report describes the prevalence of
      infection with Leishmania chagasi in Teresina at the end of the second outbreak
      and gives estimates of the number of people who became infected during the
      epidemic. Between June 1995 and May 1996, 200 households were chosen at random
      from a list of addresses covering about 93% of Teresina's urban households. In
      each household, one person over the age of 1 year was screened for Leishmania
      antibodies and skin-tested. Nearly 50% of persons had a positive leishmanin
      reaction, but only 13.9% had detectable antibodies to L. chagasi. While
      prevalence estimates based on the leishmanin skin-test increased with age
      (P<0.001), those based on serological tests showed a lesser, and non significant,
      variation with age (P=0.31). Using a geometric growth equation, and assuming that
      the annual distribution of clinical cases may serve as an approximation to what
      would have been the distribution of infections by year, we estimated that over
      320000 persons were infected during the epidemic. Little is known about the
      epidemiology of VL in urban areas, where social networks, population density, and
      relationships of housing with the natural environment are more varied and complex
      than in the rural scene. In those areas, control interventions have failed to
      eliminate transmission of the parasite and prevent new epidemics. Further
      epidemiological studies of VL in urban areas might be needed to inform control
      actions.

PMID- 12062789
TI  - Genetic variability of the main intermediate host of the Schistosoma mansoni in
      Brazil, Biomphalaria glabrata (Gastropoda: Planorbidae) assessed by SSR-PCR.
AB  - The genetic variability of Brazilian Biomphalaria glabrata populations was
      studied using SSR-PCR. This technique is a variant of the polymerase chain
      reaction (PCR), which consists of using a single primer directed towards
      microsatellite regions under high stringency reaction conditions. Twenty snails
      of each population from eight distant Brazilian localities were analyzed.
      Morphology and PCR-RFLP were used for previous specific identification of the
      snails. Bands generated after gel electrophoresis of the SSR-PCR products of each
      snail were used to study intra- and interpopulation genetic variability. Fifty
      five prominent bands were considered in a pairwise band comparison for the
      determination of genetic variability. Genetic variability was greater between
      populations than within populations. Snail populations from the field and the
      laboratory presented almost no genetic differences. No relationship between
      genetic variability and geographic distance was found. SSR-PCR proved to be a
      good alternative molecular tool for the population study of B. glabrata.

PMID- 12062790
TI  - Gall bladder and extrahepatic bile duct changes in Opisthorchis viverrini
      infected hamsters.
AB  - Opisthorchis viverrini infection is associated with several hepatobiliary
      diseases, but few reports have described extrahepatic lesions in opisthorchiasis.
      We therefore sequentially investigated histological changes of the gall bladder
      and extrahepatic bile duct in hamsters infected with 25 (group 1), 50 (group 2)
      and 100 (group 3) metacercariae for up to 180 days. Acute inflammatory reactions,
      including congestion, neutrophil and eosinophil infiltration, occurred in the
      gall bladder as early as day 7 of groups 2 and 3 and on day 14 in group 1; the
      extrahepatic bile ducts exhibited the changes on day 3 post-infection (p.i.).
      Mononuclear cell infiltration, mucus hypersecretion and fibrosis were gradually
      observed thereafter. Active inflammation reached a plateau at approximately 60
      days in all infected groups. The well-established chronic histological changes of
      the gall bladder and extrahepatic bile duct were fibrosis and mononuclear cell
      infiltration with lymphoid aggregation and, additionally, ductal dilatation for
      the latter. Overall, the pathological changes in the extrahepatic bile duct were
      more severe than those in the gall bladder for the same dose and period of
      infection. The results demonstrate that pathological changes in the gall bladder
      and extrahepatic bile duct do occur in O. viverrini infection and may be
      extrapolated to human infection.

PMID- 12062791
TI  - In vitro cultivation and characterization of Leishmania chagasi amastigote-like
      forms.
AB  - For the first time, we have reported the establishment and serial propagation of
      an axenic culture of Leishmania chagasi amastigote-like forms. Parasites were
      characterized by microscopic evaluation and by the expression of two stage
      specific genes, A2 and Ldccys2 amastigote-specific cysteine protease. The
      differentiated amastigote-like forms were maintained by serial cultivation.

PMID- 12062793
TI  - An in vitro system for assessing the sensitivity of Plasmodium vivax to
      chloroquine.
AB  - Following earlier observations on short-term culture of Plasmodium vivax, an in
      vitro test system has been developed for assessing the parasite's sensitivity to
      chloroquine. Fresh isolates with predominantly young trophozoites are diluted
      1:19 with a (v/v=1/1) mixture of RPMI 1640 and Waymouth medium. The blood-medium
      mixture (BMM) is inoculated into the predosed microtitre plates before incubation
      in a candle jar. Incubation for 30 or 42 h yielded the best results. Incubation
      for 18 or 24 h was generally insufficient for an adequate development of the
      parasites. The reading of the test is based on stage-specific differential counts
      in the Giemsa-stained pre-incubation and post-incubation thick films, the
      evaluation on log-probit analysis of drug-related inhibition of parasite
      development. The test system has been evaluated on 200 fresh P. vivax isolates in
      an area with satisfactory clinical-parasitological response to chloroquine. At 30
      or 42 h incubation 121 isolates (61.5%) showed adequate control growth and
      yielded valid sensitivity tests. Complete inhibition of parasite development
      occurred within the concentration range of 40-1280 nM. The mean EC50 for 30 h of
      incubation was 50.3 nM, as compared to 49.7 nM with 42 h of incubation. The
      geometric mean cut-off concentration of parasite development was 488 nM with 30 h
      of incubation as against 470 nM with 42 h of incubation.

PMID- 12062794
TI  - Serological evidence for remarkably variable prevalence rates of Toxoplasma
      gondii in children of major residential areas in United Arab Emirates.
AB  - The major objective of this study was to determine the seroprevalence rate of
      Toxoplasma gondii in children citizens of United Arab Emirates (UAE) main
      residential areas. Questionnaire information, clinical data and blood samples
      were obtained from 1006 primary school children residence of seven out of nine
      districts of UAE. ELISA was used for detection of antibodies against the
      immunodominant surface antigen (SAG1) of T. gondii. The sensitivity and
      specificity of the employed ELISA were 98.4 and 99.1%, respectively using 'Eiken'
      latex agglutination test as a reference test. The seroprevalence rates were
      remarkably variable in different residential areas and ranged between 3.5% for
      Dubai and 34.6% for Sharjah, with an overall prevalence of 12.5% for the seven
      districts. Rear of ruminants at home and consumption of raw milk associated
      significantly (P<0.05) with exposure to T. gondii. UAE children exposed to T.
      gondii infection had a significantly higher hepatomegaly rate (P<0.05) and
      complained more of various symptoms at the time of sampling (P<0.01) compared to
      unexposed children. This study urges for more population studies to further
      elucidate the prevalence rates of toxoplasmosis in UAE in relation to age,
      gender, place of residence and risk factors.

PMID- 12062792
TI  - Toxicity of lapachol and isolapachol and their potassium salts against
      Biomphalaria glabrata, Schistosoma mansoni cercariae, Artemia salina and Tilapia
      nilotica.
AB  - The toxicity of soluble derivatives (potassium salt) of lapachol and isolapachol
      in different stages of the life cycle of Schistosoma mansoni is evaluated. The
      potassium salts of isolapachol and lapachol showed significant molluscicidal
      activity against the adult snail (LC90<7 ppm) and snail egg masses (LC90<3 ppm).
      Cercaricidal assays revealed strong activities for both compounds. Lethality
      assays against brine shrimp eggs (Artemia salina Leach) indicated very high
      toxicity for the potassium salt of isolapachol (LC90=1.54 ppm), differently from
      the potassium salt of lapachol that can be considered non toxic (LC90=176.3 ppm).
      The same tendency is observed with piscicidal activity, for which the isolapachol
      salt has showed higher toxicity. The obtained selectivity ratios concerning LC50
      and LC90 for lapachol, in relation to Tilapia nilotica lethality assay are 2.33
      and 1.26, respectively. Despite the piscicidal toxicity, the use of the salt of
      lapachol can be recommended for field tests in Schistosomiasis, with caution.

PMID- 12062795
TI  - A marked seasonality of malaria transmission in two rural sites in eastern Sudan.
AB  - The ecology of Anopheles arabiensis and its relationship to malaria transmission
      was investigated in two villages in eastern Sudan. Seasonal malaria case
      incidence was compared with the number of vectors detected and with climatic
      variables. Following the end of the short rainy season in October the number of
      A. arabiensis detected dropped gradually until February when neither outdoor
      human bait trapping nor indoor spray catches revealed any mosquitoes. Vectors re
      appeared in June as humidity rose with the onset of rain. Despite the apparent
      absence of the vector at the height of the long, hot dry season between February
      and May, sporadic asymptomatic malaria infections were detected in the two
      villages. The low endemicity of malaria in the area was reflected by the
      relatively low total September-December parasite and sporozoite rates (15 and
      1.4%, respectively) measured in the villages. The entomological inoculation rate
      (EIR) was estimated to be around two to three infective bites per person per
      year, although heterogeneity in the transmission indices of malaria between the
      two villages was observed. The implications of these patterns of anopheline
      population dynamics for the epidemiology and control of malaria in eastern Sudan
      are considered.

PMID- 12062796
TI  - Leishmania infantum MON-98: infection in a dog from Alto Douro, Portugal.
AB  - We report the isolation of Leishmania infantum zymodeme MON-98 in Portugal, its
      first known occurrence outside the focus of El Agamy, Egypt. One dog found to be
      infected with Acanthocheilonema dracunculoides during a survey of canine
      filariosis in the Alto Douro region, north-east Portugal, was also discovered to
      have Leishmania in bone marrow. The isolated strain was identified by isoenzyme
      analysis. A search for other possible cases of L. infantum MON-98 infection in
      dogs, vectors and particularly humans is necessary to establish the real
      epidemiological importance of this zymodeme in the endemic region of Alto Douro.

PMID- 12062797
TI  - Nitrogen regulation in Saccharomyces cerevisiae.
AB  - Yeast cells can respond to growth on relatively poor nitrogen sources by
      increasing expression of the enzymes for the synthesis of glutamate and glutamine
      and by increasing the activities of permeases responsible for the uptake of amino
      acids for use as a source of nitrogen. These general responses to the quality of
      nitrogen source in the growth medium are collectively termed nitrogen regulation.
      In this review, we discuss the historical foundations of the study of nitrogen
      regulation as well as the current understanding of the regulatory networks that
      underlie nitrogen regulation. One focus of the review is the array of four GATA
      type transcription factors which are responsible for the regulation the
      expression of nitrogen-regulated genes. They are the activators Gln3p and Nil1p
      and their antagonists Nil2p and Dal80p. Our discussion includes consideration of
      the DNA elements which are the targets of the transcription factors and of the
      regulated translocation of Gln3p and Nil1p from the cytoplasm to the nucleus. A
      second focus of the review is the nitrogen regulation of the general amino acid
      permease, Gap1p, and the proline permease, Put4p, by ubiquitin mediated
      intracellular protein sorting in the secretory and endosomal pathways.

PMID- 12062798
TI  - Human cytomegalovirus immediate early proteins and cell growth control.
AB  - It is widely accepted that small DNA tumor viruses, such as adenovirus, simian
      virus 40 and papillomavirus, push infected cells into S-phase to facilitate the
      replication of their genome. Until recently, it was believed that the large DNA
      viruses (i.e. herpesviruses) functioned very differently in this regard by
      inducing a G(1) arrest in infected cells as part of their replication process.
      However, studies over the last 6-8 years have uncovered striking parallels (and
      differences) between the functions of the major immediate early (IE) proteins of
      at least one herpesvirus, human cytomegalovirus (HCMV) and IE equivalents encoded
      by small DNA tumor viruses, such as adenovirus. Similarities between the HCMV
      major IE proteins and adenovirus IE proteins include targeting of members of the
      RB and p53 families and an ability of these viral factors to induce S-phase in
      quiescent cells. However, unlike the small DNA tumor virus proteins, individual
      HCMV IE proteins target different RB family members. HCMV also encodes several
      other IE gene products as well as virion tegument proteins that act early during
      infection to prevent an infected cell from replicating its host genome and from
      undergoing apoptosis. Here, we review the specifics of several HCMV IE proteins,
      two virion components, and their functions in relation to cell growth control.

PMID- 12062799
TI  - Generation of multiple farnesoid-X-receptor isoforms through the use of
      alternative promoters.
AB  - Bile acid biosynthesis is regulated by both feed-forward and feedback mechanisms
      involving a cascade of nuclear hormone receptors. Feed-forward regulation of the
      rate limiting enzyme in bile acid biosynthesis is provided by oxysterols through
      liver-X-receptor alpha (NR1H3), while feedback regulation is provided by bile
      acids through farnesoid-X-receptor (FXR) (NR1H4). The Syrian golden hamster
      provides a useful model for studying lipid metabolism. The hamster metabolizes
      and transports dietary cholesterol in a similar manner to humans, with the
      resulting lipid profile being more similar to the human profile than that of
      other rodent models. Cloning of Fxr from Syrian golden hamster revealed four
      hamster Fxr splice variants that altered the N-terminal activation domain or the
      hinge region between the DNA and ligand binding domains. Human genomic sequence
      and data from hamster Fxr were used to identify and clone a novel human FXR
      isoform resulting from the use of an alternative promoter. RNA expression
      analysis indicates that the two human FXR isoforms are differentially expressed
      in developmental and tissue-specific patterns and are likely to provide a
      mechanism for cell-specific FXR-dependent transcriptional activity.

PMID- 12062801
TI  - Molecular cloning and expression study of Xenopus latent TGF-beta binding protein
      1 (LTBP-1).
AB  - Latent transforming growth factor beta binding protein-1 (LTBP-1) is important in
      regulating the localization and activation of transforming growth factor beta. In
      this paper is reported the isolation of the full-length Xenopus LTBP-1 cDNA from
      screening a neurula embryo cDNA library. Sequence analysis of XLTBP-1 cDNA
      revealed an open reading frame of 4518 bp encoding a 1398 amino acid protein with
      a molecular mass of 154.1 kDa and an isoelectric point of 4.65. The Xenopus XLTBP
      1 shares 61 and 65% amino acid identity with the mouse and human LTBP-1,
      respectively. It contains 17 epidermal growth factor-like motifs and four eight
      cysteine repeats (8-Cys). RNase protection assay revealed that XLTBP-1 is a
      maternal and zygotic gene, while whole-mount in situ hybridization analysis
      performed on embryos at different stages showed that during early Xenopus
      development, XLTBP-1 mRNA is expressed in the Spemann organizer, prechordal and
      chordal mesoderm, and later on in the organizer derived tissues. These findings
      suggest an important role for XLTBP-1 in embryo axis formation.

PMID- 12062800
TI  - Regulation of transcription of the human prepronociceptin gene by Sp1.
AB  - Nociceptin/orphanin FQ is a recently discovered neuropeptide and the endogenous
      ligand for opioid receptor-like-1. The promoter region of the precursor protein
      prepronociceptin (ppN/OFQ) has been cloned and sequenced. We have previously
      shown that a stretch of 110 bases immediately 5' to the first intron 23 bp
      upstream of the ATG start codon is responsible for significant enhancement of
      transcription of the human ppN/OFQ gene. We performed electromobility shift
      assays (EMSAs) using oligonucleotides spanning portions of the promoter region
      close to the intron to determine which DNA elements were important for
      transcriptional regulation. EMSAs using Sp1 antibody revealed a cis-acting
      regulatory element from bases 35-67 that appeared to bind Sp1 transcription
      factor and cause a shift to higher molecular weight. Deletion of this 30-bp
      region of DNA from the 1.2 kb promoter caused a significant loss of transcription
      as measured by luciferase reporter assays. Mutation of four bases at the Sp1
      binding site also induced a significant loss of transcription compared to
      wildtype constructs. Finally, an Sp1- but not Etf-binding consensus
      oligonucleotide was able to compete with the interaction of the oligo with the
      NS20Y nuclear extract. Combined with the data from the supershift EMSAs, it
      appears that Sp1 is the transcription factor binding to the GC region close to
      the intron to regulate transcription of the human ppN/OFQ gene.

PMID- 12062802
TI  - A gene trap Dissociation insertion line, associated with a RING-H2 finger gene,
      shows tissue specific and developmental regulated expression of the gene in
      Arabidopsis.
AB  - Real interesting new gene (RING) finger proteins act as E3 ubiquitin-protein
      ligases and play critical roles in targeting the destruction of proteins of
      diverse functions in all eukaryotes, ranging from yeast to mammals. Arabidopsis
      genome contains a large number of genes encoding RING finger proteins. In this
      report we describe the identification of more than 40 RING-H2 finger proteins
      that are of small size, not more than 200 amino acids, and contain no other
      recognizable protein-protein interaction domain(s). We characterize RHA2b, one of
      these small RING-H2 finger genes. A gene trap line, SGT6304, was identified to
      contain a Dissociation (Ds) insertion in RHA2b gene. No RHA2b transcript was
      detected in the homozygous SGT6304 plants. Despite the elimination of RHA2b
      function, homozygous SGT6304 plants lacked detectable growth or development
      defects, suggesting functional redundancy of RHA2b with other RING finger genes.
      Expression of RHA2b was specifically active in vascular tissue and in upper
      pistil of inflorescence as well as in root tip and shoot apical meristem region.
      Potential functions of ubiquitin-proteolysis pathway in vascular formation and in
      fertilization are discussed.

PMID- 12062803
TI  - Pore membrane and/or filament interacting like protein 1 (POMFIL1) is
      predominantly expressed in the nervous system and encodes different protein
      isoforms.
AB  - We have isolated and characterized a novel differentially spliced gene
      predominantly expressed in the nervous system, which encodes protein isoforms
      with significant homology to the alpha-actinin protein superfamily, the
      Caenorhabditis elegans UNC-53 protein and weak homology to the nuclear membrane
      protein POM121. Similar to POM121 the primary structures show a hydrophobic
      region that is likely to form one or more adjacent transmembrane segment(s).
      Indirect immunofluorescence with antibodies against a synthetic peptide gave
      staining of the nucleus. Target experiments with EGFP (enhanced green fluorescent
      protein)-fusion proteins confirmed the nuclear localization. Two further members
      of this gene family could be isolated. All three pore membrane and/or filament
      interacting like (POMFIL) genes are differentially expressed in neuronal tumor
      cell lines. In 40% of tested primary neuroblastomas expression of POMFIL1 is
      strongly reduced and after brain injury POMFIL1 protein expression is
      upregulated, indicating that POMFIL1 is involved in the process of neuron growth
      and regeneration, as well as in neural tumorigenesis.

PMID- 12062804
TI  - Two RpoT genes of Physcomitrella patens encode phage-type RNA polymerases with
      dual targeting to mitochondria and plastids.
AB  - Angiosperms possess a small family of phage-type RNA polymerase genes that arose
      by gene duplication from an ancestral gene encoding the mitochondrial RNA
      polymerase. We have isolated and sequenced the genes and cDNAs encoding two phage
      type RNA polymerases, PpRpoT1 and PpRpoT2, from the moss Physcomitrella patens.
      PpRpoT1 comprises 19 exons and 18 introns, PpRpoT2 contains two additional
      introns. The N-terminal transit peptides of both polymerases are shown to confer
      dual-targeting of green fluorescent protein fusions to mitochondria and plastids.
      In vitro translation of the cDNAs revealed initiation of translation at two in
      frame AUG start codons. Translation from the first methionine gives rise to a
      plastid-targeted polymerase, whereas initiation from the second methionine
      results in exclusively mitochondrial-targeted protein. Thus, dual-targeting of
      Physcomitrella RpoT is caused by and might be regulated by multiple translational
      starts. In phylogenetic analyses, the Physcomitrella RpoT polymerases form a
      sister group to all other phage-type polymerases of land plants. The two genes
      result from a gene duplication event that occurred independently from the one
      which led to the organellar polymerases with mitochondrial or plastid targeting
      properties in angiosperms. Yet, according to their conserved exon-intron
      structures they are representatives of the molecular evolutionary line leading to
      the RpoT genes of higher land plants.

PMID- 12062805
TI  - Rat zinc-fingers and homeoboxes 1 (ZHX1), a nuclear factor-YA-interacting nuclear
      protein, forms a homodimer.
AB  - Zinc-fingers and homeoboxes 1 (ZHX1) is a protein which interacts with the
      activation domain of the A subunit of nuclear factor-Y. To analyze the
      physiological role(s) of ZHX1, we searched ZHX1-interacting protein(s) using a
      yeast two-hybrid system. The rat counterpart of ZHX1 cDNAs was cloned from an
      ovarian granulosa cell complementary DNA (cDNA) library, indicating that ZHX1 is
      able to form a homodimer. An analysis of the nucleotide sequence and its deduced
      amino acid sequence show that rat ZHX1 consists of 873 amino acid residues.
      Northern blot analysis shows that ZHX1 messenger RNA is expressed ubiquitously
      and that the level in the ovary are not regulated by gonadotropins. Furthermore,
      transfection experiments with green fluorescence protein (GFP) expression vectors
      into human embryonic kidney HEK293 cells reveal that full-length ZHX1 fused to
      the GFP is localized in the nuclei. Thus, we report on the molecular cloning,
      expression and characterization of full-length rat ZHX1 cDNA.

PMID- 12062806
TI  - Cloning and identification of the promoter of the tobacco Sar8.2b gene, a gene
      involved in systemic acquired resistance.
AB  - Expression of the Sar8.2 gene family is induced by salicylic acid (SA) in tobacco
      during induction of systemic acquired resistance. Expression of Sar8.2b, one
      member of this 12-member family, was detected as early as 12 h after treatment
      with SA and was maximal 36 h after SA treatment. In NahG transgenic tobacco
      plants, benzothiadiazole and dichloroisonicotinic acid induced expression of
      Sar8.2b but SA did not, suggesting that expression of the Sar8.2b gene is SA
      dependent. Several putative cis-acting elements were found in the Sar8.2b gene
      promoter region, including an as-1 element and GT-1 and Dof binding sequences. We
      constructed a series of progressive deletion mutations in the Sar8.2b promoter
      region linked to the beta-glucuronidase (GUS) coding region and analyzed GUS
      activities by stable expression in transformants of Arabidopsis thaliana.
      Deletions between -728 and -927 bp or between -351 and -197 bp of the promoter
      region resulted in a significant reduction in GUS activity induced by SA
      treatment as shown in stable transformants of A. thaliana. The -197 bp fragment
      of the promoter region was found to confer a relatively low level of GUS activity
      induced by SA treatment in stable expression of transformants in A. thaliana. The
      results suggest that 927 bp of the Sar8.2b gene promoter confers full promoter
      activity and that cis-acting elements required for high-level SA-inducible
      expression of the Sar8.2b gene may exist within the regions -728 to -927 bp and 
      197 to -351 bp.

PMID- 12062807
TI  - Ocular development-associated gene (ODAG), a novel gene highly expressed in
      ocular development.
AB  - Complementary DNA (cDNA) arrays were used to detect highly expressed messenger
      RNA (mRNA) at postnatal day 2 (P2) and P10 in the mouse eye, and several clones
      highly expressed at P2 were isolated. We focused among them on a novel gene, the
      ocular development-associated gene (ODAG), which was down regulated at P10. The
      expression around birth was subsequently confirmed by reverse transcription
      polymerase chain reaction. Mouse ODAG cDNA encodes a protein of 266 amino acids.
      Human ODAG cDNA and genomic structure were identified by basic local alignment
      search tool analysis of the GenBank database with mouse ODAG. Mouse ODAG-specific
      mRNA expression was detected in various mouse tissues within the eye at P2 and
      P7, whereas it was not detected anywhere at P14, suggesting that ODAG may play a
      role in eye development.

PMID- 12062808
TI  - Characterization and expression analyses of the mouse Wiskott-Aldrich syndrome
      protein (WASP) family member Wave1/Scar.
AB  - Characterization of multiprotein complexes involved in actin remodeling and
      cytoskeleton reorganization is essential to understand the basic mechanisms of
      cell motility and migration. To identify proteins implicated in these processes,
      we have isolated the mouse Wave1/Scar gene, a member of the Wiskott-Aldrich
      syndrome protein (WASP) family. The mouse Wave1 gene was physically localized on
      chromosome 10 and spans over 12 Kb comprising eight exons and seven introns. The
      mouse Wave1 complementary DNA encodes a predicted 559 amino acid protein, with a
      SCAR homology domain, a basic domain, a proline-rich region, a WASP homology
      domain and an acidic domain conserved in the orthologous proteins. The Wave1
      transcription initiation site was mapped 210 base pairs upstream of the ATG
      translational start site. The presumptive proximal promoter contains putative
      consensus binding sites for E2 basic helix-loop-helix transcription factors,
      hepatocyte nuclear factor-3beta, S8 homeodomain protein, zinc finger
      transcription factor MZF-1, and an interferon-stimulated response element.
      Northern analysis demonstrated a strong expression of a unique approximately 2.6
      Kb Wave1 transcript in brain tissue, and in situ hybridization showed restricted
      expression to Purkinje cells from the cerebellum and pyramidal cells from the
      hippocampus. Characterization and expression analyses of the murine Wave1 gene
      provide the basis toward functional studies in mouse models of the role of Wave1
      in neuronal cytoskeleton organization.

PMID- 12062809
TI  - Cysteine and tyrosine-rich 1 (CYYR1), a novel unpredicted gene on human
      chromosome 21 (21q21.2), encodes a cysteine and tyrosine-rich protein and defines
      a new family of highly conserved vertebrate-specific genes.
AB  - A novel human gene has been identified by in-depth bioinformatics analysis of
      chromosome 21 segment 40/105 (21q21.1), with no coding region predicted in any
      previous analysis. Brain-derived DNA complementary to RNA (cDNA) sequencing
      predicts a 154-amino acid product with no similarity to any known protein. The
      gene has been named cysteine and tyrosine-rich protein 1 gene (symbol cysteine
      and tyrosine-rich 1, CYYR1). The CYYR1 messenger RNA was found by Northern blot
      analysis in a broad range of tissues (two transcripts of 3.4 and 2.2 kb). The
      gene consists of four exons and spans about 107 kb, including a very large intron
      of 85.8 kb. Analysis of expressed sequence tags shows high CYYR1 expression in
      cells belonging to the amine precursor uptake and decarboxylation system. We also
      cloned the cDNA of the murine ortholog Cyyr1, which was mapped by a radiation
      hybrid panel on chromosome 16 within the region corresponding to that containing
      the respective human homolog on chromosome 21. Sequence and phylogenetic analysis
      led to identification of several genes encoding CYYR1 homologous proteins. The
      most prominent feature identified in the protein family is a central, unique
      cysteine and tyrosine-rich domain, which is strongly conserved from lower
      vertebrates (fishes) to humans but is absent in bacteria and invertebrates.

PMID- 12062810
TI  - Construction of targeted single copy lac fusions using lambda Red and FLP
      mediated site-specific recombination in bacteria.
AB  - A simple method for the construction of targeted transcriptional and
      translational fusions to the lac operon using FLP mediated site-specific
      recombination is described. Conditional plasmids containing promoterless lacZY
      genes and the FLP recognition target (FRT) site in both orientations were
      constructed for generating transcriptional fusions. Similarly, a plasmid used to
      create translational fusions was constructed in which the endogenous
      translational start of lacZ has been removed. These plasmids can be transformed
      into strains containing a single FRT site, which was previously integrated
      downstream of the promoter of interest using the lambda Red recombination method.
      The FLP protein produced from a helper plasmid that contains a conditional origin
      of replication promotes site-specific recombination between the FRT sites,
      resulting in an integrated lac fusion to the gene of interest. Transcriptional
      fusions to the Salmonella typhimurium genes sodCII and sitA were constructed
      using this method and shown to respond appropriately to mutations in the
      respective regulatory genes, rpoS and fur. Translational fusions were also
      constructed using this method. In this case, expression of beta-galactosidase was
      dependent on translation of the target protein. Given that the FLP recombinase
      does not require host factors for function and that this method requires no
      molecular cloning, this method should be applicable for the analysis of gene
      expression in a variety of organisms.

PMID- 12062811
TI  - Expression and characterization of Xenopus laevis SRY-related cDNAs,
      xSox17alpha1, xSox17alpha2, xSox18alpha and xSox18beta.
AB  - Sox is a large family of genes related to the sex-determining region Y gene
      (designated as the SRY gene). Sox genes encoding DNA-binding transcriptional
      factors are found in many animals and are involved in developmental events. In
      this study, we newly isolated and sequenced novel Sox cDNAs from African clawed
      frog (Xenopus laevis). Five clones isolated here were classified into four
      distinct Sox genes designated as xSox17alpha1, xSox17alpha2, xSox18alpha and
      xSox18beta. All four belong to a subtype of SOX family, type F. The cDNA
      xSox17alpha1 contains essentially the same nucleotide sequence as that identified
      as Sox17alpha in a previous work (Cell 91 (1997) 397), whereas xSox17alpha2 is a
      distinct gene with high homology to xSox17alpha1. The clones, xSox18alpha and
      xSox18beta, are highly homologous to each other over the entire nucleotide
      sequences. The xSox18alpha and xSox18beta genes encode 363 and 361 amino acids,
      respectively. Genomic Southern hybridization analysis showed the existence of two
      copies of the xSox18. Northern analysis indicated that the xSox18 gene was
      expressed in the spleen and kidney and the size of the transcript was estimated
      to be 2.4 knt. Electrophoretic mobility shift assays indicated that recombinant
      xSox18 polypeptide was capable of binding to the HMG consensus nucleotide
      sequence, AACAAT.

PMID- 12062812
TI  - Genomic organization and restricted expression of the human Mona/Gads gene
      suggests regulation by two specific promoters.
AB  - Monocytic adaptor (Mona) also known as Gads is a Grb2-related adaptor whose
      expression is restricted to hematopoietic cells. It plays an important role in
      intracellular signaling in T cells, monocytic cells, and platelets. Here we
      investigated the regulatory aspects of Mona expression in human hematopoietic
      cells. This was carried out by combining nucleotide sequence analyzes and
      experimental approaches. We confirmed that Mona expression is restricted to T
      cell, myeloid and platelet lineages. In the various cells examined, we detected
      two major Mona transcripts (1.9 and 4 kb), likely resulting from the alternative
      use of two polyadenylation sites. Consequently, Mona transcripts of the same size
      have identical 3' untranslated region (UTR), irrespective of the cell type. In
      contrast, Mona transcripts contain either 5' UTR-1A or -1B exons, that were
      detected in a cell-lineage specific manner. Thus, T cells and several myeloid
      cell lines express 5' UTR-1A-containing transcripts, whereas platelets and cell
      lines exhibiting megakaryocytic potential express 5' UTR-1B-containing
      transcripts. Interestingly, 5' UTR-1A is generated from an exon located
      approximately 45 kb upstream of exon 1B. This suggested that lineage-restricted
      transcription of the Mona gene is controlled by specific promoters. Indeed, 2-kb
      genomic fragments upstream of each 5'-UTR showed lineage-restricted ability to
      drive expression of luc reporter gene.

PMID- 12062814
TI  - Complementary DNA analysis, expression and subcellular localization of hnRNP E2
      gene in Xenopus laevis.
AB  - The cloning and sequencing of complementary DNAs corresponding to the two copies
      (a and b) of the Xenopus laevis gene for hnRNP E2 is presented. Comparison of the
      two sequences reveals that while they are somewhat divergent at the nucleotide
      level, they are very conserved at the amino acid level. The analysis also showed
      two transcripts of different length (alpha and beta), likely generated by
      alternative processing. There are indications that either gene copy can generate
      both type of transcripts. Northern blot analysis in oocytes and developing
      embryos showed that hnRNP E2 RNA is constantly present and that increases in
      amount at tadpole stage. A semiquantitative reverse transcriptase polymerase
      chain reaction analysis performed with RNA from developing embryos showed that
      long (alpha) transcript accumulation is constant during development, whereas the
      short one (beta) accumulation increases at later stages, thus determining the
      observed increase in total RNA. Nucleo-cytoplasm localization experiments
      indicated that in oocyte hnRNP E2 is exclusively cytoplasmic, whereas in somatic
      cells it is distributed in both compartments. Comparison of the amino acid
      sequence of the two X. laevis hnRNP E2 with the corresponding mammalian sequences
      shows a high homology along the molecule except for the region subjected to
      alternative splicing, which is completely different. Moreover, there are
      indications that the homologous of mammalian hnRNP E1 gene, very related to and
      derived from hnRNP E2 by retrotransposition, is not expressed or even not present
      in X. laevis, suggesting that mammalian hnRNP E1 gene may have originated after
      mammal/amphybia divergence.

PMID- 12062813
TI  - The African trypanosome cyclophilin A homologue contains unusual conserved
      central and N-terminal domains and is developmentally regulated.
AB  - We have cloned and characterized the homologue of cyclophilin A (CypA) from
      Trypanosoma brucei brucei, Trypanosoma congolense, Trypanosoma evansi and
      Trypanosoma vivax. The 1-kilobase African trypanosome CypA complementary DNA
      contains an open reading frame of 531 base pairs, corresponding to 177 amino
      acids with a calculated molecular weight of 18,700. The CypA gene is present at
      one copy/haploid genome in T. brucei, T. congolense and T. vivax and is located
      on large chromosomes (>3 Mb) in T. brucei. CypA is differentially transcribed in
      African trypanosomes and is localized in the cytosol as well as in the flagellum.
      It is also detected in the supernatant of in vitro cultivated parasites. The
      African trypanosome CypA is unique due to a ten amino acid residue N-terminus
      extension and a block that includes a three amino acid insertion around position
      100 that might result in a differently structured surface. Wild-type recombinant
      CypA and several mutants were over-expressed in Escherichia coli and purified to
      >98% homogeneity. Antisera from cattle immunized with a trypanosome fraction
      containing immunosuppressive activity react strongly against CypA. These data
      indicate that trypanosome CypA might play an important role in the establishment
      and maintenance of infections in susceptible animals.

PMID- 12062815
TI  - Construction and exploitation in model experiments of functional selection of a
      landscape library expressed from a phagemid.
AB  - Phage display has evolved during the past 15 years as a powerful technique to
      select, from libraries of peptides or proteins, binders for various targets or to
      evolve new functions in proteins. In recent years, the knowledge acquired in
      phage display technology was exploited to engineer phages as vehicles for
      receptor-mediated gene delivery. The first vectors generated provided the proof
      of the concept that development of gene delivery vehicles based on phages was
      feasible. Results obtained showed that the level of receptor ligand display was
      an essential factor that determines the efficiency of transduction and suggested
      that phagemids might be more appropriate than phages for gene delivery. However,
      due to the limitations of the existing display systems, vectors constructed up to
      now allowed only relatively low levels of ligand display. The transduction
      efficiency of these vectors was relatively poor. Here, we describe the
      construction and optimization of a new phagemid display system that was designed
      to allow the functional selection of peptides that promote gene delivery from
      phagemids in a high display format. Peptides are displayed on every copy of the
      major coat protein pVIII and are expressed from the phagemid itself. The phagemid
      is rescued as particles by a modified R408 helper phage, deficient in pVIII
      production. Besides an expression cassette for pVIII, the phagemid also contains
      the SV40 origin of replication, the GFP gene and the neomycin resistance marker.
      As a model we constructed a library of octapeptides and showed that the library
      is amenable to selection on cos-7 cells. Several selection approaches were
      investigated and a preliminary analysis of the peptides selected was carried out.

PMID- 12062816
TI  - Cloning, expression and genomic structure of human LMX1A, and variant screening
      in Pima Indians.
AB  - LIM-homeodomain containing protein LMX1A activates transcription of the insulin
      gene. The human LMX1A gene maps to 1q22-q23, a region identified as a putative
      type 2 diabetes mellitus (T2DM) locus in several different populations. We
      analyzed LMX1A as a positional and biological candidate gene for T2DM in the Pima
      Indians, in whom a linkage of T2DM to 1q21-q23 has been previously reported. In
      the present study, we describe the cloning, expression and genomic organization
      of the LMX1A gene, which is composed of 11 exons spanning approximately 151 kb.
      In addition to a transcript encoding the predicted full-length protein of 382
      amino acids, we identified two truncated cDNA forms produced via additional
      transcription start sites and alternative splicing. We identified seven single
      nucleotide polymorphisms (SNPs) throughout the LMX1A locus and determined allele
      frequency distributions in 150 diabetic and 150 unaffected Pimas. We did not find
      evidence for association of any LMX1A SNPs with T2DM and conclude that LMX1A does
      not contribute significantly to T2DM etiology in Pima Indians.

PMID- 12062817
TI  - Control of MMP-9 expression at the maternal-fetal interface.
AB  - Cytotrophoblastic cells (CTB) from first trimester placenta form columns of
      invasive CTB. This invasive behaviour is due to the ability of CTB to secrete
      matrix metalloproteinases (MMPs) since tissue inhibitor of MMP (TIMP) inhibits
      their invasiveness. Although CTB behave like metastatic cells, in vivo they are
      only transiently invasive (first trimester) and their invasion is normally
      limited only to the endometrium and to the proximal third of the myometrium. This
      temporal and spatial regulation of trophoblast invasion is believed to be
      mediated in an autocrine way by trophoblastic factors and in a paracrine way by
      uterine factors. Several types of regulators have been investigated: hormones,
      extra-cellular matrix glycoproteins and cytokines or growth factors. This review
      is not intended to be an exhaustive catalogue of potential regulators of
      trophoblastic MMP-9 secretion but is aimed at summarising the most important
      signalling pathways involved in MMP-9 regulation.

PMID- 12062818
TI  - Molecular regulation of progesterone secretion by the human corpus luteum
      throughout the menstrual cycle.
AB  - The present study examines the expression of the steroidogenic acute regulatory
      protein (StAR) within the human corpus luteum (CL) in conjunction with other
      molecules that regulate the apoptotic process of the CL. Our results indicate
      that the primary 1.6 kb StAR transcript occurs in greater abundance in early and
      mid-luteal phase compared with late luteal phase CL. Mature StAR protein (30 kDa)
      was present in lower amounts within late CL compared with early and mid-luteal
      phase. The pre-protein (37 kDa), which has been considered the active isoform to
      favor cholesterol translocation and subsequently steroid hormone synthesis, was
      also detected in lower amount in late CL. Several molecules, including pro
      inflammatory cytokines, reactive oxygen species, steroids and inducible nitric
      oxide synthase (iNOS), have been linked as pro-apoptotic regulatory agents.
      Moreover, many of these molecules diminish progesterone synthesis in human
      cultured luteal cells. Interestingly, these molecules preferentially decrease
      progesterone biosynthesis in mid and late luteal cells in culture. These data
      suggest that the inhibitory effect of these molecules, as well as the amount of
      apoptotic cells in the CL are age dependent. The number of luteal apoptotic
      cells, as well as luteal cells stained positive for iNOS, increased from early to
      late CL. To examine the effects of hCG on StAR expression and apoptosis, we used
      two models-(1) in vivo hCG administration during the late luteal phase; and (2)
      in vitro incubation of explants of late CL with hCG. hCG increased both the level
      of StAR expression and the level of anti-apoptotic protein Bcl-2 within the late
      CL. We conclude that mRNA and protein expression of StAR and bcl-2 are important
      target elements for hCG during the CL rescue.

PMID- 12062819
TI  - Mechanisms of excessive estrogen formation in endometriosis.
AB  - Estrogen is produced in a number of human tissues including the ovary, placenta
      and extraglandular sites such as adipose tissue, skin and the brain. Aromatase is
      the key enzyme that regulates estrogen formation in these tissues. Aromatase
      activity is not detectable in normal endometrium. In contrast, aromatase is
      expressed aberrantly in endometriosis and is stimulated by PGE(2). This results
      in local production of estrogen, which induces PGE(2) formation and establishes a
      positive feedback cycle. Another abnormality in endometriosis, i.e. deficient
      17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2 expression, impairs the
      inactivation of estradiol to estrone. These molecular aberrations collectively
      favor accumulation of increasing quantities of estradiol and PGE(2) in
      endometriosis. The clinical relevance of these findings was exemplified by the
      successful treatment of an unusually aggressive case of postmenopausal
      endometriosis using an aromatase inhibitor.

PMID- 12062820
TI  - IL-1beta during in vitro decidualization in primate.
AB  - The sequence of biochemical and molecular events associated with decidualization
      in the primate remain unclear. In the baboon, the sequential changes during this
      period in vivo are characterized by the downregulation of alpha-smooth actin
      followed by induction of cyclooxygenase-2 (COX-2) at the implantation site and
      the expression of insulin growth factor binding protein-1 (IGFBP-1). IGFBP-1 is
      the predominant protein in decidualized cells and is considered to be biochemical
      marker of decidualization. In the baboon the expression of IGFBP-1 requires the
      presence of a conceptus in vivo or N(6), 2'-O-dibutyryladenosine 3:5'-cyclic
      monophosphate (dbcAMP) in the presence of hormones in vitro. In addition IL
      1beta, as a possible conceptus-mediated factor, can induce IGFBP-1 expression in
      the presence of hormones following 3 days of incubation. However, if IL-1beta and
      dbcAMP are added together, IGFBP-1 expression is inhibited which resulted in IL
      1beta being considered to be "inhibitory" to decidualization. Current data
      suggest that IL-1beta can activate multiple signaling pathways that either
      positively (no exogenous cAMP) or negatively (in presence of exogenous cAMP)
      regulate IGFBP-1 gene expression and decidualization in vitro. Signaling pathways
      activated by IL-1beta following 10 min of stimulation result in the
      phosphorylation of mitogen-activated protein kinase (MAPK, specifically p38 MAPK)
      and also lead to NF-kappaB activation. The expression of COX-2 and matrix
      metalloproteinase-3 (MMP-3) genes follows after 4-6 h. The steroid hormones,
      particularly progesterone, which are critical for IGFBP-1 expression, modulate
      the activity of IL-1beta by down-regulating MMP-3 activity. Disruption of actin
      filaments enhances IGFBP-1 induction during decidualization. IL-1beta induced MMP
      3 may upregulate IGFBP-1 by initiation of cytoskeletal reorganization through
      degradation of extracellular matrix (ECM). Inhibition of IL-1beta induced
      pathways leads to reduction of IGFBP-1 expression, suggesting that IL-1beta may
      be involved in the events leading to decidualization in baboons.

PMID- 12062821
TI  - Somatic DNA alterations in endometriosis: high frequency of chromosome 17 and p53
      loss in late-stage endometriosis.
AB  - PROBLEM: Genetic predisposition to endometriosis is well established, but the
      gene(s) involved largely remain unknown. Although endometriosis is considered a
      benign disease, it displays several features similar to malignancy: altered
      morphology, disregulated growth, invasion. We hypothesize endometriosis arises as
      result of somatic DNA alterations occurring in a multi-step process, analogous to
      origin of neoplasia. Since chromosome 17 and TP53 tumor suppressor gene (TSG)
      alterations occur frequently in premalignant and malignant tissues, including
      endometrial and ovarian epithelial carcinomas, we sought to determine if similar
      somatic changes occur in late stage endometriosis. METHOD OF STUDY: To determine
      the frequencies of monosomy for chromosome 17, as well as for perturbations of
      p53 and other loci on 17, two different approaches were used. Fluorescent in situ
      hybridization (FISH) analysis was used to detect monosomy for the 17 centromere
      and for the p53 locus. For FISH, archival tissue (n=6) and fresh endometriotic
      touch preparations were prepared from women (n=8) undergoing extirpation of
      advanced stage endometriosis. Direct-labeled probes specific for p53 (17p13.1)
      and for the chromosome 17 alpha-satellite centromere region (1711.1-q11.1) were
      used to compare single glandular and stromal cells from endometriosis and normal
      tissue. DNA analysis of polymorphic DNA loci were used to detect loss of
      heterozygosity (LoH) for other loci on 17. We assessed matched endometriotic and
      normal DNA (peripheral blood) from women with severe/late stage disease (n=15),
      studying these dinucleotide markers: HGH (located on 17q22-24), D17S250 (17q11.2
      q12) and CHRNB1 (17p13.1). RESULTS: Loss of the chromosome 17 centromere
      (monosomy) was shown by FISH in some cells from all 14 endometriosis specimens,
      although in no case did every cell show monosomy 17. In 12 of 14 specimens,
      significant proportions of cells not only were monosomic for the chromosome 17
      centromere (8 to 42% of cells) but also showed loss of p53 locus. In the two
      remaining cases, p53 loss alone was observed in 8 and 14%. LoH for other alleles
      on chromosome 17 was observed less often, namely only 3 of 15 specimens for HGH,
      1 of 15 for D17S250, and 0 of 15 for CHRNB1. CONCLUSIONS: Our study indicates
      that perturbations of chromosome 17 in general and the p53 locus in particular
      occur frequently in severe/late stage endometriosis. That not all cells show loss
      of whole chromosome 17 or the p53 locus suggests somatic mutation, perhaps
      occurring late in the pathogenesis of endometriosis. Clonal evolution of
      endometriosis must depend not only on somatic mutations for p53 but also on other
      oncogenes or TSG. Alternatively, the clone could begin with a germline or somatic
      mutation involving a nonneoplastic process, followed by one or more somatic
      mutations involving an oncogene or TSG like p53. Additional candidate genes
      clearly must be evaluated in order to determine the precise role chromosome 17
      and p53 alterations play in endometriosis; however, additional genes seem
      unlikely to involve region connoted by HGH, D17S250 or CHRNB1.

PMID- 12062823
TI  - New advances in the understanding of endometriosis related infertility.
AB  - The association between endometriosis and infertility is complex. Nevertheless,
      in the absence of tubal distortion considerable evidence suggests four principle
      factors likely to contribute to subfertility. These include impaired
      folliculogenesis, decreased fertilization, inflammatory factors in follicular,
      peritoneal and reproductive tract fluid, and implantation defects. The potential
      impact of each of these is critically examined. The role of endometriomas, prior
      surgeries and donor oocytes is also discussed.

PMID- 12062822
TI  - Preimplantation genetic screening and human implantation.
AB  - In recent years, preimplantation genetic screening (PGS) has been used and
      recommended to increase the implantation rate in older women or in couples with
      previous assisted reproduction (ART) failures, to try to increase pregnancy rates
      in couples with recurrent abortions, to prevent the transmission of chromosome
      anomalies to the offspring of carriers of balanced chromosomal rearrangements, or
      even to try to decrease the incidence of trisomic births in older women. So far,
      PGS has contributed to increase the implantation rate in older women; however,
      the rate of clinical pregnancies has not increased, either in older women or in
      couples with previous ART failures. In couples with recurrent abortions, the
      pregnancy rate seems to increase, but only when the woman is young (< or =35). In
      carriers of balanced reorganizations, the prognosis is poor. Attempts to decrease
      the birth of trisomic children to older women are difficult to evaluate. This
      absence of relevant results is not related to the technique itself, which is
      quite safe, but to other still largely unknown factors.

PMID- 12062824
TI  - Physiology and culture of the human blastocyst.
AB  - The human embryo undergoes many changes in physiology during the first 4 days of
      life as it develops and differentiates from a fertilized oocyte to the blastocyst
      stage. Concomitantly, the embryo is exposed to gradients of nutrients within the
      female reproductive tract and exhibits changes in its own nutrient requirements
      and utilization. Determining the nature of such nutrient gradients in the female
      tract and the changing requirements of the embryo has facilitated the formulation
      of stage-specific culture media designed to support embryo development throughout
      the preimplantation period. Resultant implantation rates attained with the
      culture and transfer of human blastocysts are higher than those associated with
      the transfer of cleavage stage embryos to the uterus. Such increases in
      implantation rates have facilitated the establishment of high pregnancy rates
      while reducing the number of embryos transferred. With the introduction of new
      scoring systems for the blastocyst and the non-invasive assessment of metabolic
      activity of individual embryos, it should be possible to move to single
      blastocyst transfer for the majority of patients.

PMID- 12062825
TI  - Adhesion molecules and implantation.
AB  - Endometrial receptivity towards embryo implantation is a complex process that
      involves the ovary, endometrium and embryo. The dialog between the ovary and the
      endometrium provides the hormonal stimulus for establishment of a successful
      pregnancy. The hormones estrogen and progesterone act in concert to stimulate the
      expression of key molecules necessary for embryos to attach and invade. It is
      thought that initial attachment of the embryo involves cell adhesion events. The
      best characterized cell adhesion molecule on the luminal surface of the
      endometrium is the alphavbeta3 integrin. Its ligand osteopontin (OPN) is co
      localized with alphavbeta3 and may play a role in endometrial or embryo signaling
      or facilitate embryo attachment to the apical surface prior to invasion.
      Surprising new evidence suggests that these two proteins are differentially
      regulated. Acting directly on endometrial epithelium, progesterone stimulates OPN
      expression. Using a stromal-mediated paracrine mechanism, HB-EGF or other EGF
      molecules appear to stimulate epithelial alphavbeta3 expression. In this article,
      we review what is known about these two pathways.

PMID- 12062826
TI  - Viral infection of the trophoblast: time to take a serious look at its role in
      abnormal implantation and placentation?
AB  - Fragmentary evidence suggests that trophoblast viral infection may play a role in
      placental dysfunction, leading to complications including spontaneous
      miscarriage, preeclampsia, fetal growth restriction and preterm birth. Here, we
      review the mechanisms underlying differentiation and gestational age-dependent
      infection of trophoblast cells and the consequences of in vitro infection on
      trophoblast function. The relationship between trophoblast infection by common
      viruses and pregnancy outcomes is also analyzed. We conclude that there is
      sufficient evidence linking placental infection by common viruses, including
      viruses thought to be non-pathogenic or to have low pathogenicity, to indicate
      that this effect contributes to poor pregnancy outcome.

PMID- 12062827
TI  - Impact of ovarian stimulation on corpus luteum function and embryonic
      implantation.
AB  - The luteal phase has been found to be defective in virtually all the stimulation
      protocols used in in-vitro fertilization (IVF), indicating that common mechanisms
      might be involved despite the use of different drugs. A normal luteal phase is
      characterised by a normal hormonal environment, normal progesterone secretion by
      the corpus luteum and adequate endometrial secretory transformation. Luteinizing
      hormone supports the corpus luteum and luteal luteinizing hormone (LH) levels
      have been found to be reduced in human menopausal gonadotrophin (HMG),
      gonadotrophin-releasing hormone (GnRH)-agonist/HMG and GnRH-antagonist/HMG
      protocols, probably leading to an insufficient corpus luteum function.
      Supraphysiological steroid serum concentrations routinely observed in stimulated
      cycles may adversely affect LH secretion and induce a luteal-phase defect. In
      turn, these high steroid serum concentrations may advance early luteal-phase
      endometrial development leading to embryo-endometrial asynchrony and decreased
      pregnancy rates in IVF cycles.

PMID- 12062828
TI  - Human endometrial receptivity: gene regulation.
AB  - Endometrial receptivity is a self-limited period in which the endometrial
      epithelium (EE) acquires a functional and transient ovarian steroid-dependent
      status that allows blastocyst adhesion. Termed as "the window of implantation",
      this specific period opens 4-5 days after progesterone production or
      administration and closes after 9-10 days. Scientific knowledge on the
      endometrial receptivity process is fundamental for the understanding of human
      reproduction, but so far none of the proposed biochemical markers for endometrial
      receptivity has been proven to be clinically useful. In this work, we present
      strategies of cDNA analysis technologies that aim to clarify the fragmented
      information in this field. Specifically, the objective is the differential
      identification, cloning and sequencing of genes linked to endometrial receptivity
      in humans, combining differential display PCR and cDNA microarray analysis of
      endometrial epithelial-derived cell lines and endometrial samples obtained in the
      same patient 2 and 7 days after the luteinizing hormone (LH) surge (day LH+2) and
      (day LH+7), respectively.

PMID- 12062829
TI  - Towards single embryo transfer in IVF.
AB  - Assisted reproductive technologies have, during the last two decades, managed to
      overcome a majority of the reasons for infertility in both women and men. Also,
      infertility associated to a specific couple can generally be successfully
      treated. The techniques have been proven both safe and cost effective. There is,
      however, one major shortcoming: an adverse effect in terms of multiple pregnancy,
      sometimes in the high order. The present communication gives suggestions on how
      to avoid multiple pregnancy by correct application and improvement of techniques
      already utilized today. Controlled ovarian hyperstimulation, fertilization and
      culture procedures, preimplantation genetic diagnosis, freezing procedures and
      prolonged embryo culture are all techniques and applications which need
      improvement if the goal of a predominance for singletons with only occasional
      twins should be reached within a predictable future.

PMID- 12062830
TI  - New techniques on embryo manipulation.
AB  - For many years, experience has been accumulated on embryo and gamete manipulation
      in livestock animals. The present work is a review of these techniques and their
      possible application in human embryology in specific cases. It is possible to
      manipulate gametes at different levels, producing paternal or maternal haploid
      embryos (hemicloning), using different techniques including nuclear transfer. At
      the embryonic stage, considering practical, ethical and legal issues, techniques
      will be reviewed that include cloning and embryo splitting at the cleavage stage,
      morula, or blastocyst stage.

PMID- 12062833
TI  - A serious threat to evidence based resuscitation within the European Union.

PMID- 12062831
TI  - Thrombophilia and pregnancy loss.
AB  - Thrombophilia is defined as a tendency to thrombosis. The association between
      specific thrombophilic defects--both inherited and acquired--and pregnancy loss
      is a rapidly developing field. However, apart from antiphospholipid antibodies
      (aPL), an acquired thrombophilic defect, the role of other defects in the
      haemostatic pathways remains to be established. In this invited review we discuss
      the recent advances in our understanding of aPL related pregnancy loss, the
      association between genetic thrombophilic mutations and pregnancy outcome and the
      role of whole blood haemostasis testing in the investigation of women with
      recurrent miscarriage.

PMID- 12062835
TI  - The right to informed consent or the right to life.

PMID- 12062834
TI  - Consent for research in emergency situations.

PMID- 12062836
TI  - Optimising progress in resuscitation not optimising roadblocks.

PMID- 12062837
TI  - Into the hands of lawyers I commend my patients - the patients view.

PMID- 12062838
TI  - Friedrich Wilhelm Ahnefeld.

PMID- 12062839
TI  - S-100 protein as early predictor of regaining consciousness after out of hospital
      cardiac arrest.
AB  - BACKGROUND AND PURPOSE: Patients resuscitated from cardiac arrest (CA) have a
      high mortality rate. Prognostic evaluation based on clinical observations is
      uncertain and would benefit from the use of biochemical markers of hypoxic brain
      damage. The purpose of the study was to validate the use of the serum astroglial
      protein S-100 levels at admission with regard to regaining consciousness after
      out of hospital CA. METHODS: Fifty-eight patients resuscitated from out-of
      hospital CA were followed up until they regained consciousness or until their
      death or permanent vegetative state occurred. Serum samples for measurement of S
      100, using an immunoradiometric assay, were obtained at admission. RESULTS: At
      admission, the mean value+/-standard error of the mean of serum S-100 protein was
      significantly higher in patients who did not regain consciousness compared with
      patients who regained consciousness, respectively 4.66+/-0.61 microg/l and 0.84+/
      0.21 microg/l. A serum S-100 value of >0.7 microg/l at admission was found to be
      a predictor that consciousness would not be regained, with a specificity of 85%,
      a sensitivity of 66.6%, a positive predictive value of 84%, a negative predictive
      value of 78% and an accuracy of 77.6%. CONCLUSIONS: Serum S-100 protein at
      admission gives reliable and independent information concerning the short term
      neurological outcome after resuscitation; and could be a good marker of brain
      cell damage.

PMID- 12062840
TI  - Intra-aortic balloon counterpulsation in the emergency department: a 7-year
      review and analysis of predictors of survival.
AB  - BACKGROUND: Intra-aortic balloon pump (IABP) counterpulsation in cardiogenic
      shock (CS) is suggested as bridging therapy to definite emergency
      revascularization, heart transplantation and acute valvular repair. Data
      concerning the use of IABP counterpulsation in an emergency department (ED) are
      rare. PATIENTS AND METHODS: We reviewed retrospectively the charts of patients
      who had been treated by IABP counterpulsation in the ED of a tertiary care
      university hospital during a 7-year period. We analyzed indications for IABP
      treatment, complications of IABP use and studied various predictors for 30-day
      survival. RESULTS: Overall 88 (68 male) patients, median age 60 years (IQR 53-69
      years) were treated with IABP counterpulsation. CS was caused by acute coronary
      syndrome (ACS), acute cardiomyopathy decompensation of (CMP) and aortic stenosis
      (AS) in 77 (87%), ten (12%) and one (1%) patients, respectively. Complications
      attributed to the insertion or maintenance of IABP were observed in nine (10%)
      patients. Thirty four patients (38%; 24 male) survived. Compared to non
      survivors, these patients were younger (56 vs. 63 years; P<0.023) and had
      significant lower serum lactate levels before IABP insertion (3 vs. 5.5 mmol/l;
      P<0.002). Logistic regression analysis identified age (P<0.04) and serum lactate
      serum level before IABP (P<0.01) as independent predictors for survival. In the
      77 patients with ACS PTCA tended to be associated with a higher rate of survival
      (P<0.09). CONCLUSION: Initiation of IABP counterpulsation in patients with CS in
      an ED appears safe. Low levels of serum lactate and younger age were independent
      predictors of survival. In patients with ACS PTCA may contribute to improved
      outcome.

PMID- 12062841
TI  - Factors influencing the outcomes after in-hospital resuscitation in Taiwan.
AB  - BACKGROUND: The effects on prognosis of some advanced interventions established
      before cardiopulmonary resuscitation are not clear. The outcomes and patterns of
      various factors of in-hospital resuscitation are also influenced by different
      disease patterns in different areas. We studied the factors related to outcomes
      in an oriental country. MATERIALS AND METHODS: We studied the in-hospital
      resuscitation events in a tertiary medical center in Taipei city, Taiwan. All
      events and variables were recorded using the Utstein style for in-hospital
      resuscitation. We measured the influence of patients and event variables on the
      outcomes of return of spontaneous circulation (ROSC) and survival to discharge.
      RESULTS: The rate of establishing a ROSC was 67% and the rate of survival to
      discharge was 17% in the studied population. The 1-year survival rate was 3.9%.
      Only 17% of the patients resuscitated had coronary artery disease. VT/VF was the
      initial rhythm in only 13.6% patients. Nearly half (49%) of the resuscitation
      attempts took place in emergency department (ED). Patients who were already
      intubated or had received mechanical ventilation before resuscitation had reduced
      chances of achieving ROSC. (P<0.05). Favorable prognostic factors of survival to
      discharge were shorter time intervals from patient collapse to arrival of the
      resuscitation team (69 vs. 154 s, P<0.05) and to confirmation of arrest (93 vs.
      217 s, P<0.05). CONCLUSION: Intubation and mechanical ventilation already
      established before arrest implies an underlying critical illness and reduce the
      chances of ROSC. Shorter intervals from collapse to resuscitation improve the
      chance of survival to discharge. The high proportion of resuscitation events
      occurring in the ED, reflecting ED overcrowding, and low frequency of pre
      existing coronary artery disease are unique to our country.

PMID- 12062842
TI  - In-hospital cardiac arrest: what happens to the false arrests?
AB  - OBJECTIVE: To investigate the events surrounding false cardiac arrest calls and
      subsequent outcome in patients who were the subjects of such calls. METHODS: A
      retrospective review of the cardiac arrest audit database pertaining to all false
      cardiac arrest calls logged by the hospital telephone switchboard at a London
      Teaching Hospital over a 22-month period. RESULTS: There were 59 false cardiac
      arrest calls. Of these 30 calls were immediately rescinded and 29 calls were
      erroneous. An abnormality of heart rhythm was the commonest cause for an
      erroneous call. Other important causes included epileptic seizure and
      hypovolaemia secondary to blood loss (whether due to medical or surgical causes).
      Three patients who were the subject of a rescinded call and 4 patients who were
      the subject of an erroneous call died in hospital without going home. Life table
      analysis revealed that for every 10 false arrests, eight patients were alive at
      24 h, six patients were alive at 6 weeks, four patients were alive at 6 months
      and three patients were alive at 1 year. CONCLUSIONS: There is a need for a wider
      appreciation of the significance of false cardiac arrest calls.

PMID- 12062843
TI  - Do nurses and physiotherapists require training to use an automated external
      defibrillator?
AB  - Healthcare staff with the duty to perform CPR should also be capable of using an
      automated external defibrillator (AED). We investigate whether nurses and
      physiotherapists can use an AED without prior training. Subjects were tested on a
      manikin during a cardiac arrest scenario. All 15 untrained subjects could deliver
      a shock with an AED in 68.8+/-29.2 s (time+/-S.D., range, 40-169 s). Most failed
      to position the pads correctly (53%) or follow correct safety procedures (67%).
      After a standardised training session, the time to deliver a shock improved
      significantly to 48.5+/-5.5 s (range, 41-61 s, P<0.01) and all subjects placed
      the pads correctly and followed a safe defibrillation procedure. This study shows
      that nurses and physiotherapists, with no previous AED training, can deliver a
      shock with an AED. Training improves speed of shock delivery, correct pad
      placement and safety. This study suggests that it is feasible to train healthcare
      professionals to use an AED with relatively little training. This should allow
      rapid deployment of AEDs in those areas of the hospital where cardiac arrests are
      infrequent and staff do not have rhythm recognition skills.

PMID- 12062844
TI  - Patterns of external chest compression.
AB  - We studied the performance of external chest compression by 20 fourth year
      medical students on 2 study days, separated by 5-7 weeks, 4-8 months after they
      had been initially trained in cardiopulmonary resuscitation (CPR). Our hypotheses
      were (1) that a given individual would perform external chest compressions in the
      same manner each time CPR was performed and (2) that the pattern of performance
      of chest compressions would be determined, in part, by the anthropometric
      characteristics of the rescuer. A Laerdal Skillmeter Resusci-Anne CPR manikin
      chest compression transducer was interfaced with an analogue-to-digital
      conversion board in a Macintosh LC III computer. Each subject on each study day
      performed four cycles of 15 compressions and two ventilations twice, once on a
      table (which raised the surface of the manikin sternum to 95 cm) and once on the
      floor. For each individual, on each attempt, we calculated the depth and rate of
      compressions, duty cycle, peak compression velocity, time to peak compression
      velocity and time to peak compression depth. In addition, we calculated the
      regression slope of compression depth versus compression number for each cycle of
      15 chest compressions and over four cycles of compressions. Statistically
      significant correlations were observed between the first and second study days in
      each of the variables of chest compression measured, indicating that the
      performance of chest compressions was constant over time for a given individual.
      We observed that the depth of compression, duty cycle, time to peak compression,
      time to peak velocity and regression slope of depth of compressions versus
      compression number were significantly related to the height and weight of the
      rescuer.

PMID- 12062845
TI  - The position of the spine in the recovery position--an experimental comparison
      between the lateral recovery position and the modified HAINES position.
AB  - The lateral recovery position is widely used for the positioning of unconscious
      patients. Ideally, in the setting of trauma it is avoided because of concerns
      about spinal cord injury. However, unconscious individuals with unsuspected
      trauma or trauma victims attended by partially trained first-aiders may be placed
      in the recovery position, potentially endangering the cord. Excessive movement of
      the spine in the recovery position may increase the risk of spinal cord injury in
      these situations. A new recovery position, termed the modified HAINES position,
      is described and the position of the spine in this position is compared with the
      lateral recovery position. HYPOTHESIS: That the modified HAINES position results
      in less distortion of the position of the spine than the lateral recovery
      position. METHODS: Thirty-eight healthy volunteers were imaged in the two
      different positions. Measurements of rotation, flexion and lateral flexion of the
      cervical and thoraco-lumbar spine were made. Two tailed paired t-tests were
      employed to compare measurements of the two positions and a McNemar test was used
      to compare the subjects' subjective experiences. RESULTS: The modified HAINES
      position resulted in 13.0 degrees (99% CI: 7.5-18.5) less lateral flexion and
      12.6 degrees (99% CI: 9.4-15.9) less extension of the cervical spine while the
      position of the thoraco-lumbar spine was similar in both positions. Nineteen of
      28 subjects found the modified HAINES position more comfortable (not
      significant). CONCLUSION: The modified HAINES position results in a more neutral
      position of the spine making it preferable to the lateral recovery position in
      the management of patients when trauma may have occurred. Further research is
      required to ensure that the recovery positions in use today are the best
      possible.

PMID- 12062846
TI  - Effect of the cardioselective ATP-sensitive potassium channel inhibitor HMR 1883
      in a porcine model of cardiopulmonary resuscitation.
AB  - OBJECTIVE: HMR 1883 (the free acid form of HMR 1098) selectively inactivates
      myocardial ATP sensitive potassium channels, which may be a potential important
      therapeutic approach to prevent life-threatening arrhythmias. This study was
      designed to assess the effects of HMR 1883 combined with adrenaline on
      haemodynamic variables, blood gases, and cardiac arrhythmias in a porcine cardiac
      arrest model. METHODS: After 8 min of untreated cardiac arrest, followed by 1 min
      of cardiopulmonary resuscitation (CPR), 12 pigs weighing 30-40 kg were assigned
      randomly to receive either 45 microg/kg adrenaline alone (n=6), or 45 microg/kg
      adrenaline combined with 3 mg/kg HMR 1883 (n=6), followed by up to three
      defibrillation attempts 2 min later. Five minutes after return of spontaneous
      circulation, cardiac arrest was induced for 1 min, with the CPR protocol
      following as described above. All animals subsequently underwent four cardiac
      arrest intervals of 1, 2, 3, and 4 min duration which were separated by four
      episodes of 5 min of return of spontaneous circulation. RESULTS: Haemodynamic
      variables, cardiac arrhythmias in the acute resuscitation phase between
      termination of chest compressions and return of spontaneous circulation, and
      after return of spontaneous circulation in both groups were comparable throughout
      the experiment. Survival rates throughout the experiment were comparable between
      groups. Arterial blood gases, electrolyte, glucose, and lactate levels in both
      groups during the experiment indicated comparable severe metabolic acidosis, with
      increasing levels after each episode of simulated refibrillation, and subsequent
      return of spontaneous circulation. CONCLUSION: Combining HMR 1883 with adrenaline
      during CPR resulted in comparable haemodynamic variables, return of spontaneous
      circulation rates, cardiac arrhythmias, lactate and glucose levels compared with
      adrenaline alone. This indicates that injection of HMR 1883 was safe under these
      conditions.

PMID- 12062847
TI  - Dynamic computed tomography: a novel technique to study lung aeration and
      atelectasis formation during experimental CPR.
AB  - OBJECTIVE: To develop an image based technique to study the effect of different
      ventilatory strategies on lung ventilation and alveolar recruitment during
      cardiopulmonary resuscitation (CPR). DESIGN: (1) Technical development of the
      following components: (a) construction of an external chest compression device,
      which does not interfere with CT imaging, and (b) development of a software tool
      to detect lung parenchyma automatically and to calculate radiological density
      parameters. (2) Feasibility studies: three strategies of CPR ventilation were
      performed and imaged in one animal each (pigs, 25 kg): volume-constant
      ventilation (VCV), no ventilation, or continuous airway pressure (CPAP). One
      minute after induction of circulatory arrest inside the CT scanner, external
      chest compressions started at a rate of 100 cpm, and one of the ventilation modes
      was initiated. After 1 min, intravenous epinephrine was added as a bolus (40
      microg/kg), followed by a continuous infusion (13 microg/kg per min). Six minutes
      later, dynamic CT acquisitions (temporal resolution: 100 ms) commenced.
      Simultaneously, arterial blood gases, acid base status and haemodynamics were
      sampled. RESULTS: Using a modified chest compression device, dynamic CT
      acquisitions are feasible during closed-chest CPR. In three pilot experiments
      with different ventilation strategies, the dedicated software tool allowed to
      quantify ventilated, atelectatic and over-distended fractions of total lung area.
      VCV showed a large amount of atelectasis, which was recruited during every
      respiratory cycle. No ventilation led to atelectasis to govern over 50% of the
      total lung area. CPAP caused less atelectasis as VCV, and no cyclic recruitment
      and de-recruitment phenomena were observed. CONCLUSIONS: We demonstrate a novel
      experimental set up, which allows quantification of different lung compartments
      during ongoing CPR and may become useful in comparing the direct pulmonary
      effects of different ventilatory strategies in the settings of Basic and Advanced
      Cardiac Life Support.

PMID- 12062848
TI  - Osteomyelitis at the injection site of adrenalin through an intraosseous needle
      in a 3-month-old infant.
AB  - Intraosseous (IO) puncture is considered for the administration of drugs and
      fluids when vascular access cannot be achieved rapidly. Adrenaline/epinephrine,
      adenosine, crystalloids, colloids and blood products can be applied and
      administered effectively using this route during resuscitation of children. This
      technique is relatively simple with complications of <1%. These may include
      tibial fracture, lower extremity compartment syndrome and osteomyelitis. A case
      is described in which a 3-month-old male infant presented for emergency
      resuscitation requiring IO infusion utilising both tibial bones. High doses of
      adrenaline (1:1000; 0.1 mg/kg) were administered in the right tibial epiphysis
      only after the standard initial concentration (1:10000; 0.01 mg/kg) had minimal
      effect. A local inflammatory reaction was noted 24 h later in the right tibial
      region, which developed into cutaneous necrosis, and was eventually resected.
      Radiologically, no osseous lesion could be demonstrated, however, a bone
      scintigram revealed osteomyelitis. Upon surgical revision, purulent destruction
      was evident requiring removal of the epiphysis and part of the metaphysis.
      Although osteomyelitis is a rare complication which may be caused by sepsis, or
      contamination during insertion, we speculate that adrenaline in high
      concentrations may promote the development of osteomyelitis and the drug should
      be applied cautiously in more diluted concentrations.

PMID- 12062849
TI  - Automatic external defibrillators for cardiac arrest in children.

PMID- 12062850
TI  - Pathogenesis of obesity by food restriction in OLETF rats-increased intestinal
      monoacylglycerol acyltransferase activities may be a crucial factor.
AB  - Obesity was considered to be one of the causes of non-insulin-dependent diabetes
      mellitus (NIDDM). However, the mechanism responsible for obesity has not yet been
      fully elucidated. In this study, we first examined the relationship between food
      intake amount and obesity in a NIDDM model animal, and then we focused on
      triacylglycerol (TG) synthetase activity, which play important roles in
      hypertriglyceridemia (HTG) associated with obesity. Otsuka Long-Evans Tokushima
      Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity, HTG and
      insulin resistance. In this study, OLETF rats were allocated to a food-satiated
      group (satiated) or food-restricted group (to eliminate the effects of
      hyperphagia on obesity, amount of daily food intake was the same as that in their
      control strain Long-Evans Tokushima Otsuka (LETO) rats). Changes in body weight,
      body fat, intraabdominal fat weight, and TG content in liver were measured and
      biochemical blood tests and activity assay of TG synthetase (monoacylglycerol
      acyltransferase (MGAT) and diacylglycerol acyltransferase (DGAT)) were performed.
      RESULTS: (1) The body weight in the restricted OLETF rats was significantly
      decreased to 71.7% of that in the satiated OLETF rats, which was almost the same
      value as that in the LETO rats. However, body fat and intraabdominal fat weight
      were significantly increased in restricted OLETF rats and satiated OLETF rats
      compared with LETO rats. (2) Plasma TG, insulin, glucose, leptin and hepatic TG
      content were significantly higher in OLETF rats than the values in LETO rats. (3)
      MGAT activity in the small intestine from both satiated and restricted OLETF rats
      was significantly higher than that in LETO rats. DGAT activity in OLETF rats was
      not significantly different from that in LETO rats. In conclusion, the body fat
      weight and plasma TG were still significantly accelerated in OLETF rats at the
      same food intake as LETO rats. MGAT activity in the small intestine from OLETF
      rats was also significantly higher than those of LETO rats. Therefore, high MGAT
      activity in the small intestine may play an important role in HTG and obesity,
      subsequently hastening the development of NIDDM in OLETF rats.

PMID- 12062851
TI  - Early detection of infantile pre-type 1 diabetes case with transient
      hyperglycemia.
AB  - The patient was an infant with transient hyperglycemia and decreased endogenous
      insulin secretion on intravenous glucose tolerance test (IVGTT) with the
      appearance of IA-2 autoantibodies (IA-2Ab), and we speculated that he was in the
      prediabetes stage. To our knowledge, this is the first case reported to be
      diagnosed as type 1 diabetes prior to clinical onset in Japan.

PMID- 12062852
TI  - Lack of evidence of cerebral oedema in adults treated for diabetic ketoacidosis
      with fluids of different tonicity.
AB  - Each of ten adult patients consecutively admitted in DKA (diabetic ketoacidosis)
      was infused with either 0.15 or 0.12 mol/l saline as part of the treatment
      regimen. Computerized tomography (CT) scans of the brain were performed before
      treatment, and at 6-12 and 24 h together with a number of blood variables. The CT
      scans of a group of ten patients with no history of diabetes were studied as
      controls. The CT scans of all diabetic patients in DKA showed a definite increase
      in brain tissue density when compared with those of non-diabetic subjects (mean
      36.2 vs. 28.9 Hounsfield units (HU), P<0.001). This did not change with either
      fluid regimen over the first 24 h. There was a statistically significant
      difference in brain tissue density between the CT scans of patients in DKA
      compared with CT scans taken >6 months after the last episode of DKA (32.6 vs.
      25.4 HU, P<0.001). The CT scans taken >6 months after the last episode of DKA
      showed normal brain tissue density with no statistically significant differences
      from those of control scans. The density of diabetic brains on CT scanning during
      ketoacidosis is increased; this may be due to cerebral dehydration. This paper
      does not provide any evidence of cerebral oedema in adults during the treatment
      of ketoacidosis with isotonic and hypotonic fluids.

PMID- 12062853
TI  - The contribution of metformin to glycaemic control in patients with Type 2
      diabetes mellitus receiving combination therapy with insulin.
AB  - Combination therapy of oral hypoglycaemic agents and insulin is a therapeutic
      option for those who have deterioration in glycaemic control. We examined the
      contribution of metformin by withdrawing it from Type 2 diabetic patients who had
      been stabilised on combination therapy. Fifty-one subjects with Type 2 diabetes
      and secondary oral hypoglycaemic agent failure were studied in a randomised, open
      and parallel study. In the first phase of 36 weeks, subjects were stabilised on
      combined therapy of sulphonylureas and nocturnal insulin, with or without
      metformin. During the second phase, metformin was withdrawn. The primary
      variables for efficacy were HbA(1c), fasting plasma glucose and 3-point capillary
      blood glucose profiles. After stabilisation with combination therapy, those
      subjects on metformin used less insulin to maintain glycaemic control (13.7+/-6.8
      vs. 23.0+/-9.4 U/day, P=0.001) and had lower HbA(1c) values (8.13+/-0.89 vs.
      9.05+/-1.30%, P=0.003) compared with those not given metformin. Withdrawal of
      metformin therapy caused deterioration in HbA(1c) (P=0.001). This study confirms
      that metformin plays an important role in the success of the combination therapy.
      The rational use of metformin and sulphonylurea together with insulin will help
      to improve metabolic control in Type 2 diabetes patients who have secondary drug
      failure.

PMID- 12062854
TI  - Vitamin D binding protein gene and genetic susceptibility to type 2 diabetes
      mellitus in a Polish population.
AB  - Polymorphisms of the genes involved in the metabolism of vitamin D may predispose
      to type 2 diabetes mellitus (T2DM). For example, there is evidence suggesting
      that vitamin D binding protein (DBP) amino acid variants at codons 416 (aspartic
      acid-->glutamic acid) and 420 (threonine-->lysine) may affect genetic
      susceptibility to T2DM. The aims of this study are: (1) to determine the allele,
      genotype, haplotype and haplotype combination frequencies of those DBP amino acid
      variants in a Polish population and (2) to examine their role in the genetic
      susceptibility to T2DM in a Polish population. Overall 393 individuals were
      included in this study: 231 T2DM patients and 162 controls. The sequence of DBP
      exon 11, which contains both examined variants, was amplified by polymerase chain
      reaction (PCR). Alleles and genotypes were determined based on electrophoresis of
      the DNA digestion products by specific restriction enzymes HaeIII and StyI. Since
      variants of DBP were in very strong linkage disequilibrium, haplotypes could be
      assigned to phase-unknown individuals. Differences in distributions between the
      groups were examined by chi(2) test. At codon 416 the frequency of Asp/Glu
      alleles was 44.6/55.4% in T2DM patients and 40.7/59.3% in controls (chi(2)=2.1,
      d.f.=1, P=0.28). At codon 420 the frequency of Thr/Lys alleles were 69.4/30.6%
      and 71.6/28.4%, (chi(2)=0.41, d.f.=1, P=0.52), respectively. Distribution of
      genotypes, haplotypes and haplotype combinations were similar in both groups. In
      conclusion, the frequency of amino acid variants at codons 416 and 420 of vitamin
      D binding protein gene in a Polish population is similar to other Caucasian
      populations, but differs significantly from other races. No evidence was found
      for an association between DBP frequent polymorphisms and T2DM in this
      population.

PMID- 12062855
TI  - Prediction of exercise-mediated changes in metabolic markers by gene
      polymorphism.
AB  - The effects of regular physical exercise on obesity-associated metabolic
      abnormalities vary for each individual. In this study, we investigated whether
      genotypes of genes associated with obesity can predict the effects of exercise on
      changes in metabolic markers in healthy men. Healthy Japanese men (n=106)
      performed the exercise program at 50% of their maximal heart rate for 20-60 min a
      day, 2-3 days each week for 3 months. The levels of fasting plasma glucose (FPG)
      and serum leptin significantly decreased after the exercise program.
      Polymorphisms of the beta3-adrenergic receptor (beta3AR) and uncoupling protein-1
      (UCP-1) genes were analyzed with RFLP methods. In the Trp/Trp genotype of the
      beta3AR gene, the levels of serum leptin, FPG and fructosamine (FrAm) decreased
      significantly after the exercise program, but not in the Arg/Arg genotype. In the
      AG heterozygote and the GG homozygote of the UCP-1 gene, FPG and FrAm levels were
      significantly reduced, respectively. In conclusion, gene polymorphism of the
      beta3AR and UCP-1 was found to be associated with the exercise-mediated
      improvement in glucose tolerance and leptin resistance in healthy Japanese men.

PMID- 12062856
TI  - A preventative foot care programme for people with diabetes with different stages
      of neuropathy.
AB  - The aim of this study was to assess the efficacy of a preventative foot care
      programme, applied in a normal outpatient setting to decrease the incidence of
      foot ulcers in people with diabetes diagnosed as having neuropathy by neuropathy
      disability score (NDS), in relation to the severity of neuropathy based on the
      vibration perception threshold (VPT). A structured continuous preventative foot
      care programme was designed to ensure proper footwear, walking foot hygiene,
      callus care, nailcutting, water temperature checks, use of warming devices,
      bathroom surgery, foot care products and self-inspection. Continual foot-care
      education and treatment, including podiatry, were available. Evaluation was at
      least every 6 months. Diabetic patients (n=308) with neuropathy (NDS > or =6),
      72.3+/-10.7 years old, 45% men, 10.9+/-8.8 years duration of diabetes, and
      HbA(1c) 6.5+/-1.3%, without a history of foot lesions were recruited over 3 years
      and followed-up for 4.6 (3-6) years. A low risk group (n=124) had a VPT<25 V
      while 184 had a VPT > or =25 V (high risk). In all 220 patients (71%) complied
      with the programme, compliance being 76 and 68% in low and high risk groups. The
      low risk group developed nine ulcers in nine patients, and the high risk group 24
      ulcers in 19 patients. Of these eight and 19 ulcers, respectively, were in the
      non-compliant patient group, giving relative risk of 22 and eight compared with
      people attending the programme. Thus compliance with a preventative foot
      programme reduces the incidence of foot ulceration in people with diabetes with
      neuropathy. This decrease is relatively greater in patients with less severity of
      neuropathy. The simple design should be widely generalisable.

PMID- 12062857
TI  - The Australian Diabetes, Obesity and Lifestyle Study (AusDiab)--methods and
      response rates.
AB  - The Australian Diabetes, Obesity and Lifestyle Study (AusDiab) addresses the
      urgent need for data on diabetes prevalence, risk factors and associated
      conditions in Australia. Here we describe the methods used and the response rates
      obtained. AusDiab was a population-based cross-sectional survey of national
      diabetes mellitus prevalence and associated risk factors in people aged > or =25
      years, conducted between May 1999 and December 2000 in the six states and the
      Northern Territory of Australia. The study involved an initial household
      interview, followed by a biomedical examination that included an oral glucose
      tolerance test (OGTT), standard anthropometric tests, blood pressure measurements
      and the administration of questionnaires. Of the 20347 eligible people (aged > or
      =25 years and resident at the address for > or =6 months) who completed a
      household interview, 11247 (55.3%) attended for the biomedical examination. Of
      those who completed the biomedical examination 55.1% were female. Comparisons
      with the 1998 Australian population estimates showed that younger age responders
      were under-represented at the biomedical examination, while the middle-aged and
      older age groups were over-represented. Weighting of the AusDiab data for age and
      gender have corrected for this bias. AusDiab, which is the largest national
      diabetes prevalence study undertaken in a developed nation to have used an OGTT,
      provides a valuable national resource for the study of the prevalence and
      possible causes of diabetes, as well as identifying possible risk factors that
      may lead to diabetes. Furthermore, it generates the baseline data for a
      prospective 5-year cohort study. The data will be important for national and
      regional public health and lifestyle education and health promotion programs.

PMID- 12062858
TI  - Differential effect of PPARgamma2 variants in the development of type 2 diabetes
      between native Japanese and Japanese Americans.
AB  - Common type 2 diabetes mellitus is a disorder that is though to develop by
      interaction between genetic and environmental factors. Among these factors,
      peroxisome proliferator-activated receptor (PPAR)gamma gene was identified as a
      genetic element which variant form, Pro12Ala, was shown to have differential
      metabolic activity than the wild type. To elucidate the mechanism of interaction
      between genetic and environmental factors in development of type 2 diabetes, we
      analyzed prevalence and metabolic status in the context of the variant form of
      PPARgamma in 105 native Japanese and 145 Japanese American, both should have
      different environmental factors. The observed frequency of Pro-allele in Japanese
      American with diabetes was significantly higher than those with normal glucose
      tolerance (NGT) (P=0.015), while that in native Japanese with diabetes was not
      different from those with NGT. Alternatively, Japanese Americans with diabetes
      with Pro/Pro genotype had significantly higher BMI (P=0.024) and higher fasting
      serum insulin (P=0.043) level than native Japanese, showing that individuals with
      Ala-allele could be more sensitive to insulin than those with Pro/Pro genotype.
      The data with emigrants suggests the possible interaction of gene-environment in
      the development of type 2 diabetes.

PMID- 12062859
TI  - Diabetic ketoacidosis and rhino-orbital mucormycosis.
AB  - Mucormycosis often develops in immunocompromised patients, particularly in
      patients with diabetic ketoacidosis. Unless early diagnosis and treatment is
      established mucormycosis leads rapidly to death. A 38-year-old woman was admitted
      to the hospital with a severe diabetic ketoacidosis. Her clinical status improved
      in 4 days as a result of aggressive medical treatment. She has complained left
      cheek pain on the 10th day and had a swelling of her left cheek, facial edema, a
      black eschar on the palate and nasal cavity in association with visual
      disturbance and total ophthalmology in a short time. CT scan revealed left
      orbital cellulitis and pansinusitis. Excessive surgical treatment was performed
      and liposomal amphotericin-B, 4 mg/(kg day) was applied. Extensive fungal
      invasion of the orbit and the sinuses was demonstrated in the pathological
      species and Rhizomucor species were yielded with culture. Repeated superficial
      debridement was also performed. After 10 weeks, she was discharged with
      suggestion of insulin treatment and liposomal amphotericin-B with progressively
      decreasing doses. At the 13th month following the presentation, the patient was
      free of disease as confirmed by serial imaging and under good glycaemic control
      with insulin treatment. Although mucormycosis is a fatal infection, early
      diagnosis and aggressive treatment may decrease mortality.

PMID- 12062860
TI  - Increasing diabetes and vascular risk factors in a sub-urban Sri Lankan
      population.

PMID- 12062876
TI  - A new beginning for research on borderline personality disorder.

PMID- 12062877
TI  - The borderline diagnosis I: psychopathology, comorbidity, and personality
      structure.
AB  - Borderline personality disorder (BPD) is a complex and serious mental disorder
      associated with severe functional impairment, substantial treatment utilization,
      and a high rate of mortality by suicide. Recently, BPD has become a focus of
      intensifying study. In Part I of this three-part article meant to provide a
      foundation to researchers on the current status of the borderline diagnosis and
      prospects for its future development, we examine the psychopathology,
      comorbidity, and personality structure of BPD. Although the descriptive
      characteristics of BPD are well-represented by DSM-IV diagnostic criteria, other
      important aspects of BPD psychopathology are not included. The descriptive
      criteria in conjunction with semistructured interviews have, however, increased
      the ability of investigators to diagnose BPD as reliably as many Axis I
      disorders. Frequent comorbidity of BPD with Axis I disorders necessitates a broad
      assessment of psychopathology to help account for clinical heterogeneity. Because
      of the absence of evidence of the validity of the diagnostic threshold for a
      categorical diagnosis of BPD, and because of the heterogeneity within the
      diagnosis, investigators should also supplement their DSM-IV diagnoses with
      assessments of underlying personality trait structures. Although there are a
      number of competing models of personality structure, they have remarkable
      convergence on a set of three to five basic personality dimensions.

PMID- 12062878
TI  - The borderline diagnosis II: biology, genetics, and clinical course.
AB  - In Part I of this three-part article, consideration of the core features of BPD
      psychopathology, of comorbidity with Axis I disorders, and of underlying
      personality trait structure suggested that the borderline diagnosis might be
      productively studied from the perspective of dimensions of trait expression, in
      addition to that of the category itself. In Part II, we review the biology,
      genetics, and clinical course of borderline personality disorder (BPD),
      continuing to attend to the utility of a focus on fundamental dimensions of
      psychopathology. Biological approaches to the study of personality can identify
      individual differences with both genetic and environmental influences. The
      aspects of personality disorder that are likely to have biologic correlates are
      those involving regulation of affects, impulse/action patterns, cognitive
      organization and anxiety/inhibition. For BPD, key psychobiological domains
      include impulsive aggression, associated with reduced serotonergic activity in
      the brain, and affective instability, associated with increased responsivity of
      cholinergic systems. There may be a strong genetic component for the development
      of BPD, but it seems clear, at least, that there are strong genetic influences on
      traits that underlie it, such as neuroticism, impulsivity, anxiousness, affective
      lability, and insecure attachment. The course of BPD suggests a heterogeneous
      disorder. Predictors of poor prognosis include history of childhood sexual abuse,
      early age at first psychiatric contact, chronicity of symptoms, affective
      instability, aggression, substance abuse, and increased comorbidity. For research
      purposes, at least, biological, genetic, and prognostic studies all continue to
      suggest the need to supplement categorical diagnoses of BPD with assessments of
      key underlying personality trait dimensions and with historical and clinical
      observations apart from those needed to make the borderline diagnosis itself.

PMID- 12062879
TI  - The borderline diagnosis III: identifying endophenotypes for genetic studies.
AB  - Although it is generally acknowledged that borderline personality disorder (BPD)
      has a complex, multifactorial etiology with interacting genetic and environmental
      substrates, the specific genetic underpinnings of this disorder have not been
      extensively investigated. Family aggregation studies suggest the heritability for
      BPD as a diagnosis, but the genetic basis for this disorder may be stronger for
      dimensions such as impulsivity/aggression and affective instability than for the
      diagnostic criteria itself. Family, adoptive, and twin studies also converge to
      support an underlying genetic component to the disorder. An endophenotypic
      approach to defining the genetics of this complex disorder may be called for.
      Twin studies in an epidemiologic, non-clinically ascertained sample using both
      diagnostic measures and laboratory measures that can be operationalized,
      including neuropsychologic, psychophysiologic, and operationalized behavioral
      tests, may be useful. Large-scale family studies of clinically ascertained
      samples with careful diagnostic demarcation and measurement of endophenotypes in
      probands and relatives may also prove to be a promising approach. The use of
      laboratory paradigms for measures of aggression and affective instability are
      discussed in the context of such endophenotypic approaches.

PMID- 12062880
TI  - Another view of therapy for cognition in schizophrenia.

PMID- 12062881
TI  - The neurocognitive effects of low-dose haloperidol: a two-year comparison with
      risperidone.
AB  - BACKGROUND: Neurocognitive deficits are core features of schizophrenia that are
      linked to functional outcome for the disorder. Recent studies and reviews have
      concluded that newer antipsychotic medications are better for neurocognitive
      deficits than conventional antipsychotic medications; however, one difficulty in
      interpreting this literature is that the comparisons have mainly been with high
      doses of conventional medications. This study examined the neurocognitive effects
      of low-dose haloperidol compared with risperidone over a 2-year period. METHODS:
      Sixty-two patients were randomly assigned to medication (starting at 6 mg of each
      medication) and administered neurocognitive batteries six times over the course
      of follow-up. At 6 months, the mean dose of haloperidol was 5.0 mg, and the mean
      dose of risperidone was 6.0 mg. Neurocognitive data were reduced into cluster
      scores and a global summary score. RESULTS: We found no significant overall
      differences in treatment effects on the cluster scores or the global score. The
      global score revealed a significant group by time interaction, reflecting the
      fact that the haloperidol group tended to improve initially and then stay stable,
      whereas the risperidone group improved more gradually over the follow-up period.
      CONCLUSIONS: This study did not provide support for neurocognitive advantages of
      a newer antipsychotic medication over a low-dose conventional medication. We
      speculate that conventional medications may have neurocognitive benefits at low
      doses that are neutralized or reversed at higher doses.

PMID- 12062883
TI  - Two models of impulsivity: relationship to personality traits and
      psychopathology.
AB  - BACKGROUND: Impulsivity is prominent in psychiatric disorders. Two dominant
      models of impulsivity are the reward-discounting model, where impulsivity is
      defined as inability to wait for a larger reward, and the rapid-response model,
      where impulsivity is defined as responding without adequate assessment of
      context. We have compared the role of these models of impulsivity in human
      psychopathology, based on the hypothesis that rapid-response impulsivity would be
      more strongly related to other aspects of psychopathology and to impulsivity as
      described by questionnaires. METHODS: We investigated relationships between
      personality and laboratory measures of impulsivity, and between these measures
      and clinical characteristics, in parents of adolescent subjects with disruptive
      behavioral disorders (DBDs) and matched control subjects. Diagnoses were rendered
      using the Structured Interview for DSM-IV. The Barratt Impulsiveness Scale (BIS)
      was used as a trait measure of impulsivity. Rapid-response impulsivity was
      assessed using a form of the Continuous Performance Test, the Immediate Memory
      Delayed Memory Task (IMT/DMT). Reward-delay impulsivity was measured using two
      tasks where subjects could choose between smaller immediate or larger delayed
      rewards. RESULTS: Rapid-response, but not reward-delay impulsivity, was
      significantly higher in subjects with lifetime Axis I or Axis II diagnoses.
      Scores on the BIS were elevated in subjects with Axis I diagnoses and correlated
      significantly with both rapid-response and reward-delay tests, but more strongly
      with the former. Multiple regression showed that rapid-response, but not reward
      delay performance or intelligence quotient, contributed significantly to BIS
      scores. Correlations were similar in parents of control subjects and of DBD
      subjects. CONCLUSIONS: These data suggest that measures of rapid-response
      impulsivity and of reward-delay impulsivity are both related to impulsivity as a
      personality characteristic. The relationship appears stronger, however, for rapid
      response impulsivity, as measured by the IMT/DMT. Laboratory and personality
      measures of impulsivity appear to be related to risk of psychopathology.

PMID- 12062882
TI  - High-avidity human serum antibodies recognizing linear epitopes of Borna disease
      virus proteins.
AB  - BACKGROUND: The recent observation that Borna disease virus (BDV)-reactive
      antibodies from psychiatric patients exhibit only low avidity for BDV antigen
      called into question their diagnostic value and raised the possibility that
      antigenically related microorganisms or self antigens caused the production of
      these antibodies. We further characterized the specificity of these antibodies.
      METHODS: We established a peptide array-based screening test that allows the
      identification of antibodies directed against linear epitopes of the two major
      BDV proteins, the nucleoprotein (N) and the phosphoprotein (P). RESULTS: Initial
      tests employing sera of BDV-infected mice and rats or horses with Borna disease
      revealed a high specificity and sensitivity of this test. All sera recognized
      epitopes of N, P, or both. Sera of noninfected rats, mice, and horses showed no
      signals on either peptide array. Several human sera that recognized BDV antigen
      by indirect immunofluorescence contained antibodies that recognized various
      linear epitopes of one or even both BDV proteins. Remarkably, antibodies purified
      from such human serum by matrix-immobilized peptides showed high-avidity binding
      to BDV antigens when assayed by IFA or Western blotting. CONCLUSIONS: These data
      suggest that reactive antibodies found in psychiatric patients indeed indicate
      infection with BDV or a BDV-like agent. However, the poor affinity maturation of
      BDV-specific human antibodies remains unexplained.

PMID- 12062884
TI  - Parietal dysfunction is associated with increased outcome-related decision-making
      in schizophrenia patients.
AB  - BACKGROUND: Decision-making is a complex process and depends on a network of
      fronto-parietal and cingulate areas. Decision-making dysfunctions in
      schizophrenia patients are characterized by an alternation between stereotypic
      and unpredictable responses. This study tested the hypothesis that schizophrenia
      patients show less decision-making-related activation in the prefrontal and
      parietal cortex. METHODS: Fifteen schizophrenia patients were matched with
      fifteen normal comparison subjects. During functional magnetic resonance imaging
      (fMRI) scanning, subjects were tested on the two-choice prediction task
      (predicting the location of a randomly presented stimulus) and the two-choice
      response task (responding according to the location of the stimulus). RESULTS:
      Schizophrenia patients relative to comparison subjects generated more outcome
      dependent responses. Schizophrenia patients and normal comparison subjects showed
      decision-making-related activation in right prefrontal cortex, insula, anterior
      cingulate, and bilateral precuneus. Schizophrenia patients showed less activation
      in inferior, medial prefrontal, and right superior temporal cortex and more
      activation in the postcentral and inferior parietal cortex. Decision-making
      related activation in both right prefrontal and bilateral parietal cortex was
      higher in medicated compared to unmedicated schizophrenia patients. CONCLUSIONS:
      These results support the hypothesis that the interaction between prefrontal and
      parietal cortex during decision-making by schizophrenia patients is dysregulated,
      which results in an increased outcome-dependent response selection.

PMID- 12062885
TI  - A volumetric MRI study of the entorhinal cortex in first episode neuroleptic
      naive schizophrenia.
AB  - BACKGROUND: Imaging studies have frequently reported volume loss of limbic
      structures in schizophrenia, yet there appears to be no quantitative data on
      entorhinal cortex volumes in patients with neuroleptic naive first-episode
      schizophrenia. METHODS: The volume of the entorhinal cortices of 22 control
      subjects and 18 patients with neuroleptic-naive first-episode schizophrenia were
      measured from magnetic resonance images (MRI) scans using recently designed
      anatomic criteria for MRI anatomy of the entorhinal cortex. RESULTS: Smaller
      entorhinal volumes were found bilaterally in the schizophrenic patients. This
      volume loss did not correlate with items on the Positive and Negative Syndrome
      Scale. CONCLUSIONS: These data suggest early involvement of the entorhinal cortex
      in schizophrenia.

PMID- 12062886
TI  - Reduced frontotemporal functional connectivity in schizophrenia associated with
      auditory hallucinations.
AB  - BACKGROUND: We used functional magnetic resonance imaging (fMRI) to investigate
      the frontotemporal disconnection hypothesis of schizophrenia. METHODS: Eight DSM
      IV schizophrenia patients and 10 control subjects were studied with fMRI while
      they thought of the missing last word in 128 visually presented sentences. The
      fMRI data were analyzed comparing the effect of sentence completion (vs. rest)
      using a random effects analysis. RESULTS: There were no significant group
      differences in regional brain responses. Correlation coefficients between left
      temporal cortex (x = -54, y = -42, z = 3) and left dorsolateral prefrontal cortex
      (x = -39, y = 12, z = 24) were significantly lower in the schizophrenic group and
      were negatively correlated with the severity of auditory hallucinations.
      CONCLUSIONS: Previous demonstrations of hypofrontality in schizophrenia may
      reflect particular task requirements. Frontotemporal functional connectivity is
      reduced in schizophrenia and may be associated with auditory hallucinations.

PMID- 12062888
TI  - A dissociation of perception and action in normal human observers: the effect of
      temporal-delay.
AB  - Neuropsychological results support the proposal that the human visual system is
      organised into distinct processing pathways, one for conscious perception and one
      for the control of action. Here, we compare perceptual and action responses
      following a pre-response-delay. Experiment 1 required participants to reproduce
      remembered locations and found that although perceptual matches were unaffected
      by delays of up to 4 s, pointing responses were significantly biased after only 2
      s. Experiment 2 examined whether both the transport and grasp components of a
      natural prehensile movement were similarly affected by delay. Both peak wrist
      velocities and peak grip-apertures were affected equivalently by delay,
      suggesting that the two components of a prehensile movement have similar temporal
      constraints. The results from both experiments are consistent with the general
      perception-action dichotomy as originally proposed by Milner and Goodale [The
      visual brain in action, Oxford: Oxford University Press, 1995].

PMID- 12062887
TI  - Information processing characteristics in subtypes of multiple sclerosis.
AB  - The purpose of this study was to evaluate information processing characteristics
      in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58
      matched healthy controls. Using computerized tests, we investigated focused,
      divided, sustained attention, and executive function, and attempted to pinpoint
      deficits in attentional control to peripheral or central processing stages. The
      results substantiate the hypothesis that the slowing of attention-demanding
      (controlled) information processing underlying more complex cognitive skills is
      general, i.e. irrespective of type of controlled processing, with MS patients
      being 40% slower than controls. MS patients may suffer from focused, and divided
      and sustained attention deficits, as well as from compromised central processing
      stages, with secondary progressive (SP) patients showing the most extensive range
      of deficits, closely followed by primary progressive (PP) patients, while
      relapsing-remitting (RR) patients appear to be much less affected. General
      slowing appears to be highest in PP and SP type MS patients (50% slower) versus
      relapsing-remitting MS (24% slower). In contrast to most previous results,
      (complex) processing speed appeared to be robustly correlated with severity of MS
      as measured by the expanded disability status scale and with disease duration.
      Patients did much less differ in accuracy of processing from controls, suggesting
      the importance of using time strategies in planning everyday life and job
      activities to compensate for or alleviate MS-related speed handicaps.

PMID- 12062889
TI  - The influence of computer experience on visuo-motor control: implications for
      visuo-motor testing in Parkinson's disease.
AB  - Abnormalities in visuo-motor control have repeatedly been reported in Parkinson's
      disease (PD) patients. In the more recent studies, tasks measuring visuo-motor
      performance are usually computerised tasks requiring the use of a mouse-like
      manipulandum. In healthy subjects, previous computer mouse experience can
      influence performance in computerised visuo-motor tasks. We, therefore,
      investigated the potential confounding effect of mouse experience in a visuo
      motor task used in PD patients, the visuo-motor testing (VMT) system, and its
      concurrent usefulness in the diagnosis of PD. Our study population included 49
      early PD patients and 31 controls. The VMT system involves moving a pointer over
      a sinusoidal path displayed on a computer screen by moving an unseen digitiser
      mouse over a tablet. In both PD patients and controls, subjects with low mouse
      experience scored worse than subjects with high mouse experience on variables
      measuring movement accuracy, direction and speed. After correction for mouse
      experience the aforementioned deficits were still present in PD patients with low
      mouse experience. However, PD patients with high mouse experience only showed
      deficits in movement accuracy. It would seem that previous mouse experience can
      at least partly compensate for deficits in directional control and speed in PD
      patients, implying a possible role for training in the treatment of functional
      motor impairments in PD. Future studies using computerised psychomotor tasks
      should take sufficient precautions to avoid potential confounding effects of
      mouse experience. The present data further suggest that only accuracy of visuo
      motor control might be a useful parameter in the (early) diagnosis of PD.

PMID- 12062890
TI  - Are multiplication facts implemented by the left supramarginal and angular gyri?
AB  - A patient with presumed cerebral vasculitis showed preserved single digit
      multiplication facts and impaired single digit subtraction facts. Her ability to
      comprehend and manipulate numerical quantities was intact. Detailed analysis of
      her MRI-scan revealed a lesion involving the left parietal lobe including the
      supramarginal gyrus up to the intraparietal sulcus and extending posteriorly to
      involve part of the angular gyrus. This finding contradicts a previous report by
      Lee [Ann. Neurol. 48 (2000) 657] suggesting that these areas are critical for
      multiplication. In addition, this case contradicts the predicted association
      between subtraction and quantity manipulation, proposed by Dehaene's triple-code
      model [Cortex 33 (1997) 219].

PMID- 12062891
TI  - Is motor perseveration in unilateral neglect 'driven' by the presence of
      neglected left-sided stimuli?
AB  - Unilateral spatial neglect refers to a difficulty in detecting or acting on
      information in a particular region of space. When asked to cross out stimuli
      distributed across a page, patients with neglect may miss many targets on the
      left. In addition, they have a tendency to return to, and re-mark, right-sided
      targets that they have already cancelled. A recent retrospective study has shown
      this effect to be specific to unilateral neglect rather than a consequence of
      right hemisphere damage in general. Here, a consecutive group of seven right
      hemisphere neglect patients performed five versions of a standard cancellation
      task, each version differing in the quantity of left-sided information presented.
      All of the participants showed perseveration on right-sided targets in the basic
      task. A highly significant and linear reduction in perseverative behaviour was
      observed as left-sided information was removed. In a second study, left-sided
      targets were again progressively removed but, in this case, were replaced with an
      additional distractor item, keeping the total quantity of stimuli presented in
      each condition constant. Again, a significant reduction in right-sided
      perseveration was observed, indicating a high degree of selectivity to the
      effect. The results show that a difficulty in perceiving existing cancellation
      marks, or a non-spatially specific motoric perseveration, are unlikely to fully
      account for this behaviour. As the patients omitted almost all targets on the
      left side of the basic cancellation task, the results suggest a striking
      influence on apparently intentional behaviour from un-cancelled information
      within the neglected field.

PMID- 12062892
TI  - Spatial attention in agenesis of the corpus callosum: shifting attention between
      visual fields.
AB  - The role of the corpus callosum in spatially selective visual attention is
      uncertain. Research using commissurotomy and callosotomy patients has attempted
      to determine if the corpus callosum plays a role in reorienting attention between
      visual fields, as if spatial attention is unitary or divisible between the
      cerebral hemispheres. Reorienting of selective visuospatial attention within
      versus between visual fields was tested in 10 individuals with agenesis of the
      corpus callosum (ACC) and nine matched controls. Spatially focused attention to
      the most likely location of target appearance was created using both peripheral
      sensory cues and central symbolic cues in separate tests. Results demonstrated
      that individuals with ACC have significantly greater difficulty reorienting
      attention to an invalidly cued target stimulus occurring in the opposite visual
      field. However, this effect did not interact with the type of cueing (sensory or
      symbolic). Individuals with ACC did not differ from controls either with respect
      to the laterality of within-field reorientation of attention, or with respect to
      the most efficient direction of between-field shifting of attention. Since
      congenital absence of the corpus callosum significantly reduces efficiency in the
      reorienting of attention between visual fields, spatial attention cannot be
      completely unified based on a subcortical mechanism and the mobilization of
      attentional resources within each hemisphere must depend on callosal processes.

PMID- 12062893
TI  - Selective serotonin reuptake inhibitor paroxetine modulates motor behavior
      through practice. A double-blind, placebo-controlled, multi-dose study in healthy
      subjects.
AB  - We hypothesized that selective serotonin reuptake inhibitors (SSRIs) could
      modulate motor activity in healthy subjects in a dose-dependent manner. The
      effects of a single dose of paroxetine were tested in a double-blind, placebo
      controlled study. Six randomized and counterbalanced subjects performed
      behavioral tests in three sessions 1 week apart (E1, E2 and E3) at peak plasma
      concentration (5 h after drug intake). Each subject was given 20 mg or 60 mg of
      the drug, or a placebo. Tasks were the Nine Peg Hole test (three trials), Moede
      dexteritymeter (two trials), and compatible and incompatible reaction time tasks.
      The results show that at the first trials, performance did not differ after
      placebo or paroxetine intake. However, 20 and 60 mg of paroxetine improved
      performance significantly at the third trial of the Nine Peg Hole test and
      subjects receiving the drug performed 7% faster than those under placebo. An
      amount of 20 mg, but not 60 mg, of paroxetine improved dexterity significantly at
      the second trial of the Moede test and subjects performed 30% faster. Conversely,
      the drug did not affect reaction time for the compatible task and subjects were
      11% slower under 20 mg with the incompatible task. Thus, paroxetine decreased the
      ability to inhibit automatism. Thus, it was concluded that a single dose of
      paroxetine improved motor performance through practice. But negative effects
      occurred on tasks including the inhibition of an automatism. Paroxetine enhanced
      brain motor output (motor activity in S1M1) [NeuroImage, 15 (2002) 26]. This S1M1
      hyperactivation is likely to be responsible for the better performance. The brain
      effect and motor improvement were dose dependent. For both, 20 mg was the optimal
      dose.

PMID- 12062894
TI  - Egocentric body-centered coordinates modulate visuomotor performance.
AB  - Parietal damage has been hypothesized to distort the body-centered coordinate
      frame and produce the ipsilesional spatial bias characteristic of unilateral
      neglect. The present studies investigated the role of the egocentric frame in
      normal visuomotor performance by manipulating the alignment of the body midline
      in neurologically-intact adults. The results from two experiments indicate that:
      (1) rightward rotation causes a right visual field advantage in detection times
      for lateralized targets; (2) rightward rotation evokes an increase in visual
      sensitivity to right visual field targets and a decrease in sensitivity to left
      visual field targets; and (3) leftward rotation does not affect response latency
      or sensitivity, however, response criterion is mildly affected. By demonstrating
      that the alignment of the body-centered frame can induce neglect-like asymmetries
      in visuomotor performance in neurologically-intact subjects, the results support
      a role for an altered body-centered representation in clinical neglect.

PMID- 12062895
TI  - Direction and position factors in performance of line extension task by
      unilateral neglect subjects.
AB  - In this study was investigated the influence of direction and position in the
      performance of a line extension task by patients with unilateral neglect, with
      the aim of exploring the role of perceptual and premotor factors in this task.
      Twenty-three right brain damaged patients (14 patients with left unilateral
      neglect) were asked to extend horizontal lines both leftward and rightward; lines
      were presented in three different positions (left, right and central). Patients
      with neglect significantly overextended the lines in all conditions, but
      particularly toward the sagittal mid plane of the body and leftward when the line
      was presented on the right. The global overextension seem to be related to
      concomitant hemianopsia. A crucial finding in neglect group was that left
      extensions reduced progressively on passing from right through central to left
      presentation, particularly in patients with lesions involving frontal regions or
      the basal ganglia. The last finding supports the hypothesis that left
      overextension does not exclude the coexistence of both perceptual and premotor
      factors (causing directional hypometria) in left unilateral neglect.

PMID- 12062897
TI  - Zebrafish insulin-like growth factor-I receptor: molecular cloning and
      developmental expression.
AB  - The biological actions of the insulin-like growth factors (IGFs) are mediated
      primarily by the IGF-I receptor (IGF-IR), and the IGF family has been highly
      conserved throughout vertebrate evolution. In this study we report the isolation
      of a 3 kb cDNA clone for the zebrafish IGF-IR that includes the complete 3'
      untranslated region and polyA tail and mapping of the receptor gene to zebrafish
      linkage group 7. The open reading frame deduced from the cDNA sequence
      encompasses the juxtamembrane and protein tyrosine kinase portions of the
      receptor, and is 70 and 67% identical to the corresponding regions of the IGF-IRs
      of the turbot and Xenopus, respectively. By RT-PCR, zebrafish IGF-IR expression
      was detected from early blastula to early larval stages of development. Using
      whole mount in situ hybridization, IGF-IR expression was detected after
      gastrulation. Expression was evident in most tissues but was particularly evident
      in the tail, in eye and ear primordia and in the brain.

PMID- 12062896
TI  - AP-2alpha modulates human corticotropin-releasing hormone gene expression in the
      placenta by direct protein-protein interaction.
AB  - Since AP-2alpha induces the expression of hPL, hCG and other syncytiotrophoblast
      specific marker genes in cytotrophoblast cells during in vitro differentiation,
      we have examined whether AP-2alpha also induces hCRH gene expression during
      differentiation of cytotrophoblast cells. Infection of human cytotrophoblast
      cells in vitro with an adenovirus expressing AP-2alpha resulted in a twofold
      increase in hCRH mRNA levels, while infection with an adenovirus expressing a
      dominant/negative mutant of AP-2alpha inhibited basal hCRH mRNA levels by 40% and
      completely blocked the induction of hCRH mRNA by AP-2alpha. Transient
      transfection studies in AtT-20 and HepG2 cells indicated that the induction of
      hCRH mRNA levels was due, at least in part, to transcriptional activation of the
      hCRH gene. Gel mobility shift and immunoprecipitation assays strongly suggest
      that AP-2alpha induces hCRH gene expression by interacting with CREB and not by
      binding directly to the hCRH promoter.

PMID- 12062898
TI  - Regulation of the gonadotropin-releasing hormone receptor (GnRHR) by RGS
      proteins: role of the GnRHR carboxyl-terminus.
AB  - The cytoplasmic carboxyl-terminus of G-protein coupled receptors (GPCRs), absent
      in the mammalian gonadotropin-releasing hormone receptor (GnRHR), plays an
      important role in receptor expression, desensitization, internalization and
      efficiency of coupling to G proteins. Regulators of G protein signaling (RGS)
      likewise are involved in regulating GPCR-G protein mediated responses and can
      regulate transcription of other genes. In this study, we evaluate differential
      expression, ligand binding and effector coupling of the rat GnRHR (rGnRHR) and a
      chimera of rGnRHR with the pre-mammalian carboxyl domain (rGnRHR-C-tail).
      Membrane expression of the chimeric receptor and G(q)alpha and G(s)alpha-mediated
      signaling was increased 2- and 1.5-fold, respectively by RGS10, while RGS3 did
      not interfere with rGnRHR and rGnRHR-C-tail cell surface expression in spite of
      negatively regulating GnRH-stimulated G(q)alpha-mediated signaling by both
      receptors. The rGnRHR and rGnRHR-C-tail showed similar internalization rates in
      the presence of either RGS protein, indicating that the modification of rGnRHR
      expression and regulation in the presence of a carboxyl-terminus by RGS10 was not
      caused by alteration of the internalization rate. The observations in this study
      implicate the carboxyl domain of the receptor as a site of interaction for RGS10,
      but not RGS3. This is the first evidence of an altered cell surface expression
      and regulation of the GnRHR bearing a carboxyl-terminus by RGS proteins.

PMID- 12062899
TI  - Identification and functional characterization of melatonin Mel 1a receptors in
      pancreatic beta cells: potential role in incretin-mediated cell function by
      sensitization of cAMP signaling.
AB  - Melatonin receptors are expressed within the pancreatic islets of Langerhans, and
      melatonin induces a direct effect on insulin secretion ex-vivo. Here, we report
      the endogenous expression of the melatonin Mel 1a receptor in the INS-1
      pancreatic beta cell line. Pharmacological characterization of the receptor using
      a CRE-luciferase reporter gene demonstrated its functional activity in INS-1
      cells, displaying the characteristic signaling properties of the G(i/o) coupled
      receptor. Acute melatonin treatment of INS-1 cells in the presence of either
      forskolin or the incretin hormone glucagon-like peptide 1 (GLP-1) caused an
      attenuation of the responses in insulin secretion, insulin promoter activity, and
      CRE mediated gene expression, consistent with its effects in inhibiting cAMP
      mediated signal transduction. However, prolonged exposure (12 h) of INS-1 cells
      to melatonin treatment resulted in a sensitization of cAMP mediated responses to
      forskolin and GLP-1. Insulin secretion, insulin promoter activity and CRE
      mediated gene expression levels were augmented compared with responses without
      melatonin pre-treatment in INS-1 cells. In isolated rat islets, insulin secretion
      was enhanced following melatonin pre-treatment both in the absence and presence
      of GLP-1 or forskolin. This phenomenon reflects observations reported in other
      cell types expressing the melatonin Mel 1a receptor, and may represent the first
      evidence of a specific physiological role for melatonin-induced sensitization.

PMID- 12062900
TI  - Role of adenine nucleotides in insulin secretion from MIN6 pseudoislets.
AB  - Insulin secretion from MIN6 cells configured as cell aggregates by culture on a
      gelatin substrate (pseudoislets) is enhanced compared to that of MIN6 cells grown
      as monolayers on tissue culture plastic, indicating the importance of beta-cell
      to-beta-cell proximity for insulin release. In this study we have shown that
      glucose induced a biphasic release of insulin from pseudoislets, whereas the
      amplitude and duration of the responses of equivalent monolayer cells were much
      reduced. Purinergic aqonists have been implicated in intercellular communication
      between beta-cells, so we investigated whether adenine nucleotides co-released
      with insulin are responsible for the enhanced secretory responses of
      pseudoislets. We have demonstrated that MIN6 cells express purinergic A(1) and
      P2Y receptors, and that adenine nucleotides increased [Ca(2+)](i) with an
      efficacy of agonists being ATP > ADP > AMP. However, neither suramin nor the more
      selective A(1) antagonist 1,3-dipropyl-8-cyclopentylxanthine reduced glucose
      induced insulin secretion from pseudoislets, and stimulation of monolayer cells
      with a range of adenine nucleotides did not enhance glucose-induced secretion.
      These results suggest that enhanced secretion from MIN6 pseudoislets is not due
      to increased paracrine/autocrine action of adenine nucleotides.

PMID- 12062901
TI  - Stimulation of calbindin-D(9k) mRNA expression in the rat uterus by octyl-phenol,
      nonylphenol and bisphenol.
AB  - Quantification of estrogen-induced changes in the expression levels of endogenous
      genes such as pS2 and vitellogenin could be an assay to detect estrogenicity of
      chemicals. Considering its regulation by estrogen, in the present study, we
      hypothesize that the calbindin-D(9k) (CaBP-9k) gene has the possibility as a
      biomarker for estrogenic response of the environmental estrogens. We analyzed the
      time- and dose-dependent CaBP-9k mRNA expression in the immature rats by 3-day
      injection of 17beta-estradiol (E2) and alkylphenol acid [octyl-phenol (OP) and
      nonylphenol (NP)] and bisphenol A(BPA)) which are environmentally persistent and
      reported to have some estrogenic activity in experimental test systems. The
      expression of CaBP-9k mRNA was compared with uterotropic response of the
      compounds. A significant increase in CaBP-9k mRNA expression was observed when
      treated with 1000 mg/kg body weight (BW) per day of OP (18-fold versus control),
      NP (17-fold versus control) and BPA (6-fold versus control) for 3 days in dot
      blot assays. Using Northern blot analysis, a more dramatic increase of CaBP-9k
      mRNA expression was observed when treated with 1000 mg/kg BW per day of OP (132
      fold versus control) and NP (113-fold versus control) for 3 days. Treatment with
      10 and 100 mg/kg BW per day of NP and 100 mg/kg BW per day of OP for 3 days
      induced a small but significant increase in CaBP-9k mRNA expression. As expected,
      a single dose of E2 (40 microg/kg BW per day) for 3 days induced a significant
      increase in CaBP-9k mRNA expression as revealed by dot (15-fold versus control)
      or Northern blot assay (102-fold versus control). In a time response experiment
      using Northern blot assay, a significant increase in CaBP-9k mRNA expression was
      observed as early as 3 h, peaked at 6 h and continued until 72 h after treatment
      with 1000 mg/kg BW per day of OP, NP, and 48 h after treatment with 1000 mg/kg BW
      per day of BPA. A similar time-dependent response was observed when assessed by
      dot blot assay. Uterotropic response of the compounds was determined and compared
      with CaBP-9k mRNA expression. The alkylphenolic compounds induced a significant
      increase in the uterine wet weight at 1000 mg/kg BW per day of OP and NP, not
      BPA. A strong correlation between in vivo uterotropic assay and CaBP-9k mRNA
      expression assay was observed. In order to investigate the possible mechanisms by
      which the compounds regulate CaBP-9k mRNA expression, we studied the effect of
      the compound on the ERalpha mRNA level using total RNA from the treated rats. The
      alkylphenolic compounds as well as E2 stimulate the expression of ERalpha mRNA in
      a similar pattern to that of CaBP-9k mRNA in terms of dose- and time-dependent
      response. Strong regulation of CaBP-9k mRNA expression by E2 and the
      environmental estrogens and its correlation with in vivo uterotropic assay
      suggest that CaBP-9k gene can be used as a biomarker gene for assaying
      estrogenicity of putative estrogenic compounds.

PMID- 12062902
TI  - Disruption of prepulse inhibition of startle reflex in a neurodevelopmental model
      of schizophrenia: reversal by clozapine, olanzapine and risperidone but not by
      haloperidol.
AB  - Neonatal ventral hippocampal (NVH) lesions in rats have been shown to induce
      behavioral abnormalities at adulthood thought to simulate some aspects of
      positive, negative and cognitive deficits classically observed in schizophrenic
      patients. Such lesions induced a post-pubertal emergence of prepulse inhibition
      deficits reminiscent of the sensorimotor gating deficits observed in a large
      majority of schizophrenic patients. Here we have investigated the capacity of
      typical and atypical antipsychotics to reverse PPI deficits seen in NVH-lesioned
      rats. We show that three atypical antipsychotics (clozapine, olanzapine and
      risperidone) were able to reverse lesion-induced PPI deficits, in contrast to
      haloperidol, a classical neuroleptic. These results show that the NVH lesion
      model seems to be endowed with a fair predictive validity as, like in
      schizophrenic patients, PPI deficits in lesioned animals were reversed by
      atypical antipsychotics but not by the typical neuroleptic haloperidol.

PMID- 12062903
TI  - Ovarian steroid regulation of 5-HT1A receptor binding and G protein activation in
      female monkeys.
AB  - Serotonin 5-HT(1A) receptors play an important role in serotonin
      neurotransmission and mental health. We previously demonstrated that estradiol
      (E) and progesterone (P) decrease 5-HT(1A) autoreceptor mRNA levels in macaques.
      In this study, we questioned whether E and P regulate 5-HT(1A) binding and
      function and G(alpha) subunit protein expression. Quantitative autoradiography
      for 5-HT(1A) receptors and G proteins using [3H]8-OH-DPAT and [35S]GTP-gamma-S,
      respectively, was performed on brain sections of rhesus macaques from four
      treatment groups: ovariectomized controls (OVX), E (28 d), P (28 d), and E (28 d)
      plus P (the last 14 d) treated. Western blot analysis for G(alpha) subunits was
      performed on raphe extracts from cynomolgus macaques that were OVX or OVX treated
      with equine estrogens (EE, 30 months). In the hypothalamus, E or E + P but not P
      alone decreased postsynaptic 5-HT(1A) binding sites. In the dorsal raphe nucleus
      (DRN), E, P, and E + P treatments decreased 5-HT(1A) autoreceptor binding. The Kd
      values for 8-OH-DPAT were the same for each treatment group. Both the basal and
      the R-(+)-8-OH-DPAT stimulated [35S]GTP-gamma-S binding were decreased during
      hormone replacement whereas the coupling efficiency between the receptor and G
      proteins was maintained. Finally, EE treatment reduced the level of G(alphai3),
      but not G(alphai1), G(alphao), and G(alphaz) in the DRN. In conclusion, these
      observations suggest that ovarian hormones may increase serotonin
      neurotransmission, in part, by decreasing 5-HT(1A) autoreceptors, 5-HT(1A)
      postsynaptic receptors, and the inhibitory G proteins for intracellular signal
      transduction.

PMID- 12062904
TI  - Modulatory effects of galanin in the lateral bed nucleus of the stria terminalis
      on behavioral and neuroendocrine responses to acute stress.
AB  - The neuropeptide galanin has been identified as a possible
      neurotransmitter/neuromodulator within the central nervous system. In the present
      study, a potential role for galanin in the lateral bed nucleus of the stria
      terminalis (BSTL) in modulating behavioral and neuroendocrine responses to an
      acute stress was investigated. In the first experiment, acute immobilization
      stress induced anxiety-like behavioral responses in rats, measured on the social
      interaction and elevated plus-maze tests. Immobilization stress decreased both
      social interaction time and open arm exploratory behavior on the elevated plus
      maze. Bilateral administration of the galanin antagonist M40 (1.0 nmole/0.2
      microl) into BSTL immediately prior to stress exposure attenuated the anxiogenic
      like effects of immobilization stress, restoring both social interaction time and
      exploration of open arms to control levels. Administration of the antagonist
      alone had no effect on baseline behavior of unstressed control rats in either
      test, suggesting that the modulatory effect of galanin elicited during stress is
      not exerted tonically in unstressed animals. In the second experiment,
      immobilization stress produced an increase in plasma adrenocorticotropic hormone
      (ACTH) that was also attenuated by bilateral administration of M40 into BSTL
      prior to stress. These results suggest that during stress, the neuropeptide
      galanin exerts a modulatory effect in the BSTL, facilitating behavioral and
      neuroendocrine components of the acute stress response.

PMID- 12062905
TI  - Effects of cocaine self-administration on striatal dopamine systems in rhesus
      monkeys: initial and chronic exposure.
AB  - The purpose of this study was to examine the time course of changes in dopamine
      D(1)- and D(2)-like receptor densities in monkeys self-administering cocaine.
      Experimentally naive adult male rhesus monkeys (n = 22) were divided into a food
      reinforcement group (n = 6), in which responding was maintained by food
      presentation, or into four cocaine self-administration groups (n = 4/group),
      based on dose (0.03 or 0.3 mg/kg per injection) and duration of exposure (5 or
      approximately 100 sessions). After the last session, monkeys were euthanized,
      brains were removed, frozen, and coronal sections through the striatum, rostral
      to the anterior commissure, were processed for D(1) ([3H]SCH23390) and D(2)
      ([3H]raclopride) receptor autoradiography. Compared with controls, there was no
      effect of 5 days of cocaine self-administration on D(1) and D(2) receptors. In
      monkeys with extensive cocaine histories, D(1) receptor densities were
      significantly increased relative to controls in some parts of the striatum, while
      D(2) receptor densities were significantly decreased throughout the striatum.
      These findings demonstrate that chronic cocaine self-administration produces
      neuroadaptations in dopamine systems, but that these changes do not occur in a
      parallel fashion.

PMID- 12062906
TI  - Neonatal damage of the ventral hippocampus impairs working memory in the rat.
AB  - We investigated if a developmental lesion of the ventral hippocampus, studied
      previously as an animal model of schizophrenia, impairs performance in working
      memory tests related to the prefrontal cortex. Adult rats with a neonatal or
      adult excitotoxic lesion of the ventral hippocampus were tested in a continuous
      delayed alternation and a discrete paired-trial variable-delay alternation task.
      Performance of rats with the neonatal lesion was impaired as compared with
      control rats on both tasks, whereas performance of rats with the adult lesion was
      not altered in either task. The pattern of impaired performance, that worsened
      with increasing delays in neonatally lesioned rats, resembled that reported
      previously in animals with adult lesions of the medial prefrontal cortex. These
      results indicate that an early developmental, but not adult hippocampal, insult
      impairs performance in tasks sensitive to the integrity of the prefrontal cortex,
      and suggest that working memory may be compromised by neonatal damage of the
      ventral hippocampus.

PMID- 12062907
TI  - Plasticity in hippocampal peptidergic systems induced by repeated
      electroconvulsive shock.
AB  - The regulated secretion of bioactive peptides requires the coordinated actions of
      a variety of gene products ranging from peptide precursors to post-translational
      processing enzymes and the cytosolic machinery involved in vesicle exocytosis. To
      evaluate the role of plasticity of peptidergic processes in the clinical response
      to electroconvulsive treatment, we monitored expression of a peptide
      (neuropeptide Y, NPY), a post-translational processing enzyme (peptidylglycine
      alpha-amidating monooxygenase, PAM) and a cytosolic component involved in peptide
      secretion and neurite extension (kalirin) in the hippocampus. Adult male rats
      were subjected to single or repeated electroconvulsive shock. In general, levels
      of NPY, PAM and kalirin mRNA showed similar transient increases after acute and
      repeated electroconvulsive shock. In contrast, repeated, but not acute,
      electroconvulsive shock brought about widespread changes in protein expression.
      Increased amounts of NPY and PAM accumulated in mossy fibers, and dentate granule
      cell dendrites contained increased amounts of NPY, PAM and kalirin. CA1 pyramidal
      neurons expressed increased amounts of PAM and kalirin, with an accumulation of
      both proteins in their dendrites. Scattered interneurons contained increased
      levels of NPY and PAM after acute and repeated shocks. However, scattered
      interneurons contained increased levels of kalirin only after repeated shocks.
      The distinctly different effects of repeated vs. acute electroconvulsive shock
      support an important role for peptidergic plasticity in the therapeutic effects
      observed following electroconvulsive treatment.

PMID- 12062908
TI  - Effects of amphetamine and evoked dopamine release on [11C]raclopride binding in
      anesthetized cats.
AB  - The effects of halothane and ketamine anesthesia on [11C]raclopride binding were
      assessed in the cat striatum at basal conditions and after drug- or
      depolarization-induced dopamine (DA) release using Positron Emission Tomography.
      At baseline, Scatchard analyses revealed that the higher [11C]raclopride binding
      found under halothane anesthesia was mainly attributable to a higher radioligand
      apparent affinity. Decreased [11C]raclopride binding was demonstrated following
      amphetamine under ketamine but not under halothane anesthesia. Under ketamine
      anesthesia transient DA overflows induced by direct stimulations of DA neurons
      through an intracerebral electrode induced transient changes in [11C]raclopride
      binding with a remarkable spatiotemporal accuracy. No effect was observed under
      halothane anesthesia. The failure to detect competition between DA and
      [11C]raclopride for binding on D(2)-receptors under halothane anesthesia might
      reflect, as already reported for other brain receptor systems, a halothane
      promoted conversion of D(2)-receptors to a state of lower affinity for DA. It is
      suggested that the affinity state of receptors is a factor to be considered in in
      vivo ligand-activation studies.

PMID- 12062909
TI  - Respiratory responses to intravenous infusion of sodium lactate in male and
      female Wistar rats.
AB  - In patients with panic disorder or premenstrual dysphoria, anxiety attacks can be
      triggered by intravenous administration of sodium lactate. Since respiratory
      symptoms, such as hyperventilation and shortness of breath, are characteristic
      features of spontaneous as well as lactate-induced panic, an involvement of
      central or peripheral chemoreceptors in this reaction has been suggested. In the
      present study, we examined to what extent intravenous infusion of sodium lactate
      influences respiratory parameters in freely moving male and female Wistar rats.
      Prompted by clinical reports suggesting that the susceptibility to spontaneous
      and lactate-induced anxiety may be influenced by the menstrual cycle, we also
      investigated if the effect of lactate on respiration in female rats is estrus
      cycle-dependent. Male and ovariectomized female rats exposed to sodium lactate
      displayed a larger increase in respiratory rate than rats given an infusion of
      saline. In intact female rats, the response to lactate infusion was significantly
      more pronounced in the diestrus phase than in the proestrus/estrus phase of the
      cycle. It is concluded that sodium lactate is a respiratory stimulant in rat, and
      that this effect is influenced by female sex steroids.

PMID- 12062910
TI  - The functional neuroanatomy of Tourette's syndrome: an FDG PET study III:
      functional coupling of regional cerebral metabolic rates.
AB  - Functional coupling of regional cerebral metabolic rates for glucose measured
      with [18F]-Fluoro-2-deoxy-D-glucose PET was compared in 18 drug-free patients
      with Tourette's Syndrome (TS) and 16 age- and sex-matched control subjects.
      Pearson product-moment correlation matrices containing correlations between
      metabolic rates in regions sampled throughout the brain were generated
      independently for TS patients and controls and compared. Significant differences
      between Z-transformed correlation coefficients were used to identify group
      differences, and revealed that the connectivity of the ventral striatum was most
      severely affected in TS. Changes in the coupling of other brain areas-primary
      motor areas, somatosensory association areas, and insula-also appeared to
      differentiate TS patients and controls. Evaluation of interrelationships between
      cortico-striato-thalamo-cortical circuits revealed the existence of functional
      connections between the motor and lateral orbitofrontal circuits in both groups,
      however, a reversal in the pattern of these interactions differentiated TS
      patients and controls. In controls, activity in these circuits appeared to be
      negatively correlated-i.e. increased activity in one is associated with relative
      inactivity the other. In TS patients, on the other hand, activity in the motor
      and lateral orbitofrontal circuits appears to be positively coupled. These
      results lend further credence to the hypothesis that altered limbic-motor
      interactions represent a pathophysiological hallmark of this disease.

PMID- 12062911
TI  - Pharmacogenetics of tardive dyskinesia: combined analysis of 780 patients
      supports association with dopamine D3 receptor gene Ser9Gly polymorphism.
AB  - Variability among individuals in their therapeutic response to psychotropic drugs
      and in susceptibility to adverse effects is considerable. Pharmacogenetics
      addresses the contribution of genetic factors to this variability. An important
      focus of interest in pharmacogenetics has been on candidate genes that play a
      role in susceptibility to the antipsychotic drug-induced adverse effect, tardive
      dyskinesia (TD). Four published studies have reported an association between a
      serine (ser) to glycine (gly) polymorphism in exon 1 of the dopamine D3 receptor
      gene (DRD3) and TD; three failed to replicate this finding and one found an
      insignificant trend. We examined the association in a pooled sample of 780
      patients (317 with TD and 463 without TD) drawn from 6 research centers, who were
      divided into 8 groups based on their population origin. The analysis employed
      stepwise logistic regression so as to allow confounding effects of group, age,
      and gender to be taken into account. TD was significantly associated with DRD3
      gly allele carrier status (x(2)=4.46, df 1, p =.04) and with DRD3 genotype
      (x(2)=6.62, df 2, p =.04) over and above the effect of group. Similar positive
      effects were observed when controlling for age and gender (x(2)=5.02, df 1, p
      =.02 for gly allele carrier status; x(2) = 7.51, df 2, p =.002 for genotype).
      Examining abnormal involuntary movement scores as a continuous variable, we found
      that patients homozygous for the gly allele had significantly higher scores than
      ser-gly heterozygotes (p =.006) or ser-ser homozygotes (p <.0001). We also
      performed a meta-analysis that included, besides the groups in the combined
      analysis, three other published studies on DRD3 and TD. The Mantel-Haenszel
      pooled odds ratio for DRD3 gly allele carrier status increasing susceptibility to
      TD was 1.33 (95% CI 1.04-1.70, p =.02); the cumulative pooled estimate showed an
      odds ratio of 1.52 (95% CI 1.08-1.68, p <.0001). These findings support a small
      but significant contribution of the DRD3 ser9gly polymorphism to TD
      susceptibility that is demonstrable over and above population effects and the
      effect of age and gender on the phenotype.

PMID- 12062912
TI  - Early changes in prefrontal activity characterize clinical responders to
      antidepressants.
AB  - Previous studies have shown that changes in brain function precede clinical
      response to antidepressant medications. Here we examined quantitative EEG (QEEG)
      absolute and relative power and a new measure, cordance, for detecting regional
      changes associated with treatment response. Fifty-one adults with unipolar
      depression completed treatment trials using either fluoxetine or venlafaxine vs.
      placebo. Data were recorded at baseline and after 48 h and 1 week on drug or
      placebo. Baseline and change from baseline values were examined for specific
      brain regions in four subject groups (medication and placebo responders and
      nonresponders). No regional baseline QEEG differences were found among the
      groups; there also were no significant changes in theta power over time. In
      contrast, medication responders uniquely showed significant decreases in
      prefrontal cordance at 48 h and 1 week. Clinical differences did not emerge until
      after four weeks. Subjects with greater changes in cordance had the most complete
      8-week responses. These findings implicate the prefrontal region in mediating
      response to antidepressant medications. Cordance may have clinical applicability
      as a leading indicator of individual response.

PMID- 12062913
TI  - The epidemiology of silica, silicosis and lung cancer: some recent findings and
      future challenges.

PMID- 12062914
TI  - A case-control study of lung cancer in relation to silica exposure and silicosis
      in a rural area in Japan.
AB  - PURPOSE: In southeast Okayama Prefecture, Japan, there have been reports of a
      high prevalence of silicosis among refractory brick production workers. Recently,
      a high mortality rate of lung cancer among the local residents has been observed.
      Therefore, a population based case-control study was conducted concerning the
      relationship between silica, silicosis, and lung cancer using multiple cancer
      controls. METHODS: Cases and controls were restricted to male subjects and
      information was obtained from death certificates from 1986 to 1993 in the area.
      Three categories of deceased control groups were selected: a series of deaths
      from liver cancer, colon cancer, and cancers of other organs, which was assumed
      not to be related to silica exposure. Age and smoking habits were adjusted by
      stratified analysis using the Mantel-Haenszel odds ratio estimates. Unconditional
      logistic regression analysis was also conducted to control potential confounding
      factors; such as age and smoking habits. RESULTS: The age-, smoking-adjusted odds
      ratios were 1.94 (0.94-4.43) for the colon cancer control group, 2.13 (1.19-3.85)
      for the other cancer control group related to silica exposure, and 2.94 (1.30
      8.90) and 2.69 (1.43-5.37) related to silicosis, respectively. The direct
      weighted average using the estimates for colon and the other cancer controls was
      2.06 (1.29-3.29) for silica exposure, and 2.77 (1.60-4.77) for silicosis.
      Histological or cytological types of lung cancer cases were obtained from 64.1%
      of the subjects (118/184). As for the histologic type of lung cancer, small cell
      carcinoma was higher among those who had been silica-exposed workers than the
      unexposed lung cancer cases and the data from the general Japanese population. On
      chest x-ray findings, elevated lung cancer mortality compared with cancers other
      than lung cancer was demonstrated among patients without large opacities.
      CONCLUSIONS: Silica exposure increased the lung cancer mortality in the area. A
      high lung cancer mortality rate in the area could be explained by silica exposure
      and silicosis prevalence in this area.

PMID- 12062915
TI  - Patterns of lung function in asymptomatic nonsmoking men and women in the
      People's Republic of China.
AB  - PURPOSE: To evaluate patterns of lung function in healthy, working Chinese men
      and women in different geographic areas of the People's Republic of China (PRC).
      METHODS: We conducted lung function tests on 2926 asymptomatic, never smoking
      Chinese men and women aged 35-56 years residing in or around Beijing and
      Guangzhou. Within each of these locations, separate urban and rural samples were
      recruited. RESULTS: Age and height adjusted lung function was greater in Beijing
      than in Guangzhou, and within each city for residents of rural vs. urban areas.
      Among women, estimated rates of lung aging were greater in Beijing than in
      Guangzhou, and in urban vs. rural areas. Both FEV(1) and FVC exhibited a
      curvilinear association with body mass index. CONCLUSIONS: Lung function data
      from this largely working cohort exhibited marked geographic and urban-rural
      differences in this never smoking, adult Chinese cohort. Such variation is not
      uncommon and may reflect differences in body size, diet, and environmental and
      occupational exposures across these different settings. Caution should be used in
      applying published reference equations to populations from different parts of the
      PRC.

PMID- 12062917
TI  - Alcohol consumption, family history of hematolymphoproliferative cancer, and the
      risk of non-Hodgkin's lymphoma in men.
AB  - PURPOSE: To investigate the association between alcohol consumption and the risk
      of non-Hodgkin's lymphoma (NHL) and to examine whether the association is
      modified by a family history of hematolymphoproliferative cancer (HLPC). METHODS:
      Data on white men from two population-based case-control studies of NHL conducted
      in Iowa/Minnesota and Kansas were pooled for this analysis. Information on
      alcohol consumption, family history of HLPC, and other factors was obtained by
      interviewing 792 cases and 2193 controls or, if deceased, their next-of-kin.
      Logistic regression models were used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: There was no clear association between NHL
      and the use of alcohol, beer, hard liquor, or wine. The relationship, however,
      may differ according to a family history of HLPC. Alcohol use was not associated
      with the risk of NHL in men without a family history of HLPC (ORs = 0.8 and 0.9
      for men consuming alcohol < or = median and > median, respectively), the presence
      of a family history in the absence of alcohol use was associated with a slightly
      increased risk (OR = 1.4; 95% CI 0.8-2.5), whereas risks of NHL among men with a
      positive family history were 2.1 (CI 1.0-4.7) for men consuming alcohol < or =
      median (13.7 g/day) and 2.8 (1.3-5.9) for men consuming alcohol greater than
      median. CONCLUSIONS: The present data found no clear association between alcohol
      consumption and the risk of NHL among men without a family history of HLPC,
      whereas alcohol intake was associated an elevated risk in men with a positive
      family history. The finding of effect modification of the alcohol-NHL association
      by a family history of HLPC is novel and requires confirmation.

PMID- 12062916
TI  - Compliance with physical activity guidelines: prevalence in a population of
      children and youth.
AB  - PURPOSE: To use objective monitoring of physical activity to determine the
      percentages of children and youth in a population that met physical activity
      guidelines. METHODS: A total of 375 students in grades 1-12 wore an accelerometer
      (CSA 7164) for seven consecutive days. Bouts of continuous activity and
      accumulation of minutes spent in physical activity at various intensities were
      calculated to determine how many students met three physical activity guidelines.
      RESULTS: Over 90% of students met Healthy People 2010, Objective 22.6 and nearly
      70% met the United Kingdom Expert Consensus Group guideline, both of which
      recommend daily accumulation of moderate physical activity. Less than 3% met
      Healthy People 2010, Objective 22.7, which calls for bouts of continuous vigorous
      physical activity. For the United Kingdom Expert Consensus Group guideline,
      compliance decreased markedly with age, but gender differences were not
      statistically significant. CONCLUSIONS: Prevalence estimates for compliance with
      national physical activity guidelines varied markedly for the three guidelines
      examined. Objective monitoring of physical activity in youth appears to be
      feasible and may provide more accurate prevalence rates than self-report
      measures.

PMID- 12062919
TI  - The incidence and prevalence of pressure ulcers among elderly patients in general
      medical practice.
AB  - PURPOSE: The objective of this study was to estimate the period prevalence and
      incidence of pressure ulcer among those 65 years of age and older. METHODS: We
      used a patient-record database called the General Practice Research Database
      (GPRD). Subjects were 65 years of age and older and cases were ascertained based
      on strict inclusion and exclusion criteria. The accuracy of the ascertainment
      strategy was estimated using mailed physician-answered questionnaires. Annual
      period prevalence and age-specific incidence were estimated per 100 person-years
      with exact 95% confidence intervals (CI). RESULTS: The accuracy of our
      ascertainment strategy was excellent, with a positive predictive value of 100%
      (95% CI: 92%,100%) and negative predictive value of 95% (85%, 95%). Over 200,000
      person-years of data were analyzed. The annual period prevalence of pressure
      ulcer among those 65 years of age and older varied from 0.31% to 0.70%. The
      incidence varied significantly with advancing patient age from 0.18 to 3.36 per
      100-person years (p < 0.001) but was not associated with gender (p = 0.95).
      CONCLUSIONS: Pressure ulcers are seen in the general practice setting. They are
      most likely to occur in those over 85 years of age. Preventative strategies
      within the general practice setting should concentrate on the oldest of the
      elderly.

PMID- 12062918
TI  - Smoking, quitting, and mortality in a Chinese cohort of retired men.
AB  - PURPOSE: To examine the relationship between smoking, quitting, and mortality in
      older Chinese men. DESIGN AND METHODS: A cohort analytic study was carried out in
      Xi'an, China. A total of 1268 retired male military cadres aged 60 or older were
      examined in 1987 and followed for 12 years. RESULTS: At baseline, 388 men were
      never-smokers, 461 were former smokers, and 419 were current smokers. Through May
      1999, a total of 299 had died. The relative risks [95% confidence intervals (CI)]
      for ever-smoking, after adjusting for age, blood pressure, body mass index, total
      cholesterol, triglycerides, alcohol drinking, exercise and existing diseases, for
      deaths resulting from all causes, chronic obstructive pulmonary disease (COPD),
      lung cancer, and coronary heart disease (CHD) were, respectively, 1.34 (1.02
      1.76), 3.23 (0.95-10.91), 2.31 (0.95-5.61), and 1.60 (0.81-3.19). The risks
      increased significantly with increasing amount and duration of smoking. Compared
      with current smokers, former smokers had lower risks of total mortality (excess
      risk reduction of 56%) and from CHD death, but had higher risks for COPD death.
      CONCLUSIONS: Smoking is a major cause of death in older Chinese and quitting can
      save lives. Early recognition of the significance of COPD symptoms followed by
      prompt quitting should be emphasized in the control of the growing tobacco
      epidemic.

PMID- 12062920
TI  - The effect of timing when seeking permission to access personal health services
      utilization records.
AB  - PURPOSE: To determine if the timing for requesting signed permission to access
      personal health services utilization records affects authorization or survey
      response rates. METHODS: A screening question about in-principle willingness to
      permit access to personal health services utilization records was included in a
      mail-based survey of two Australian female samples (n = 292). Half of the surveys
      for each sample also included a separate form to be signed to approve access. For
      the other half the form was not included, but an authorization form was sent
      subsequently. RESULTS: Around 30% of participants signed the authorization form
      and there was no significant difference between the randomized groups [ relative
      risk (RR) = 0.95, 95% confidence interval (CI) = 0.72-1.25). However, the
      response rate to the postal survey was significantly higher for the group who
      received the form after returning the questionnaire (60% compared to 46%; RR =
      1.31, 95% CI = 1.06-1.62). CONCLUSIONS: A two-staged approach, with a time lag
      between seeking in principle permission to access personal health services
      utilization records and requesting signed authorization, does not affect
      authorization rates. In addition, it results in a significantly higher survey
      response rate than if an authorization form is included with the survey.

PMID- 12062922
TI  - Self-rated health and its relation to all-cause and cardiovascular mortality in
      southern Germany. Results from the MONICA Augsburg cohort study 1984-1995.
AB  - PURPOSE: Studies worldwide show that self-rated health (SRH) is a robust
      predictor of mortality among the elderly. Only few studies have focussed on a
      middle-aged population and no such study has been reported from Germany. This
      study examined the association between SRH and mortality in a middle-aged,
      population based cohort from Germany, using data from the MONICA (Monitoring
      Trends and Determinants in Cardiovascular Diseases) Augsburg project. METHODS:
      The cohort comprises 1521 men and 1498 women aged 35-64; they were followed over
      11 years from 1984-1995. Participants provided extensive data on medical
      conditions and cardiovascular risk factors through interviews and examinations.
      SRH was assessed globally and in comparison to those of the same age. We
      estimated relative hazards for mortality from all-causes and cardiovascular
      disease according to self-ratings of health. RESULTS: Among males the adjusted
      hazards rate ratio (HRR) of mortality from all-causes was 1.5 (95% CI 1.1-2.2)
      for combined fair/poor perceived health compared with good/excellent health.
      Women with fair/poor ratings had no increased risk of dying (HRR = 1.1, 95% CI
      0.7-1.9). Men who perceived worse health than persons of the same age showed an
      adjusted HRR of 1.7 (95% CI 1.0-2.9) as compared to those perceiving better
      health; in women the adjusted HRR was 1.9 (95% CI 1.0-3.7). The adjusted hazards
      for dying from cardiovascular diseases in men were 1.3 (95% CI 0.8-2.1) for those
      perceiving fair/poor and 1.7 (95% CI 0.7-3.7) for those perceiving worse health.
      CONCLUSIONS: Self-rated health was a predictor of mortality in a middle-aged
      German population and contains information that is not entirely reflected in
      underlying medical conditions and risk factors. Self-assessments of health in
      comparison to individuals of the same age were stronger and more consistently
      associated with mortality. Global self-ratings of health and self-ratings in
      comparison to those of the same age may measure slightly different dimensions and
      the effect of self-rated health may differ among men and women.

PMID- 12062921
TI  - Subclinical atherosclerosis and estimated glucose disposal rate as predictors of
      mortality in type 1 diabetes.
AB  - PURPOSE: To investigate the usefulness of ischemic resting electrocardiogram
      (ECG), ankle brachial index (ABI) <0.8, ankle brachial difference (ABD) > or = 75
      mm Hg (a marker of peripheral medial arterial wall calcification), and estimated
      glucose disposal rate (eGDR) (a marker for insulin resistance) for predicting
      mortality risk in the context of standard risk factors. METHODS: Data are from
      participants in the Pittsburgh Epidemiology of Diabetes Complications Study of
      658 subjects with childhood onset Type 1 diabetes of mean age 28 years (range 8
      48) and duration of diabetes 19 years (range 7-37) at baseline. Deaths were
      confirmed by death certificates. RESULTS: There were 68 deaths from all causes
      during 10 years follow-up. In univariate analysis, the mortality hazard ratios
      and 95% confidence intervals associated with ischemic ECG (6.7, 3.7-12.1), the
      lowest quintile of eGDR (i.e., the most insulin resistant) (6.7, 4.1-10.9), ABI
      <0.8 (2.5, 1.1-5.9), and ABD > or = 75 mm Hg (6.7) were only marginally less than
      those conveyed by pre-existing coronary artery disease (8.4, 4.7-15.2) or overt
      nephropathy (7.6, 4.5-12.9). Ischemic ECG and eGDR were independent mortality
      predictors, together with duration of diabetes, coronary artery disease, overt
      nephropathy, nonhigh density lipoprotein cholesterol, and smoking history. If
      serum creatinine was available, it entered, and glycosylated hemoglobin replaced
      eGDR. CONCLUSIONS: Estimated GDR and ECG ischemia are strong predictors of
      mortality in type 1 diabetes and may be useful in the identification of those at
      risk.

PMID- 12062923
TI  - Desquamative inflammatory vaginitis: an exploratory case-control study.
AB  - PURPOSE: To investigate potential risk factors for desquamative inflammatory
      vaginitis (DIV), a rare but severe form of vaginitis. We are aware of no other
      controlled studies of DIV. METHODS: We conducted a case control study comparing
      DIV cases (n = 47), identified from the Wayne State University Vaginitis Clinic,
      to friend controls. For some variables, cases were also compared to 1432 women
      participating in a random digit dialing survey. RESULTS: Most cases reported that
      their last episode of DIV caused at least some pain (76.9%) and worry (73.1%).
      Cases were more likely than either friend or population controls to report (ORs
      from population controls) a history of vulvovaginal candidiasis (OR = 4.40, 95%
      CI 2.24, 8.65), bacterial vaginosis (OR = 25.58, 95% CI 15.91, 41.15), or pelvic
      inflammatory disease (OR = 16.90, 95% CI 8.26, 34.55); use of oral contraceptives
      (OR = 4.91, 95% CI 2.11, 11.43); use of hormone replacement therapy (OR = 4.74,
      95% CI 2.69, 8.37); and laparoscopic procedures (OR = 22.24, 95% CI 11.46,
      42.69). CONCLUSIONS: Future studies should be conducted to explain the
      association with fertility surgeries, hormone usage, and other urogenital
      conditions; to clarify the timing of these associations; and to identify other
      factors related to DIV.

PMID- 12062924
TI  - Reliability of selected measures of nicotine dependence among adolescents.
AB  - PURPOSE: To examine the test retest reliability, internal consistency, and
      convergent construct validity of selected measures of nicotine dependence (ND)
      among adolescents. METHODS: Self-reports of sociodemographic characteristics and
      smoking behavior were collected in a convenience sample of 238 high school
      students aged 13 to 19 years. ND was measured in the Hooked on Nicotine Checklist
      (HONC), the Stanford Dependence Index (SDI) and in 45 new items identified in
      consultation with experts and focus group interviews with adolescent smokers.
      RESULTS: Test retest reliability among past 3-month smokers indicated good to
      excellent reliability coefficients for HONC items (kappa 0.61 to 0.93), except
      one item that tapped feelings of depression on withdrawal (kappa = 0.34).
      Intraclass correlation coefficients for SDI items ranged from 0.71 to 0.77. Test
      retest reliability coefficients for the 45 new items ranged from 0.20 to 0.90.
      The HONC and SDI demonstrated good internal consistency (Cronbach's alpha = 0.90
      and 0.78, respectively). Convergent construct validity against cigarette exposure
      was demonstrated for the HONC, SDI, and most of the 45 new items. CONCLUSIONS:
      The HONC and SDI demonstrated excellent and good psychometric properties,
      respectively. Most of the 45 new items hold promise as indicators of ND in youth,
      and should be further investigated.

PMID- 12062925
TI  - Mobilization of intracellular calcium in kidney epithelial cells is inhibited by
      lead.
AB  - The effect of lead (Pb) on intracellular calcium (Cai) after stimulation with
      agonists was studied in Madin-Darby canine kidney (MDCK) cells. In response to
      the agonist ADP, the levels of Cai increased by approximately threefold in MDCK
      cells bathed in a buffer with calcium (Ca) or in a buffer with nominal Ca. Pb
      inhibited the response to ADP in MDCK cells bathed in either buffer. The
      inhibition by Pb was observed after a 5 and 20-min exposure to Pb, but not after
      2-min. Very high concentrations of ADP did not reverse the effects of Pb.
      Concentrations of Pb of 1 microM or more inhibited the response to ADP.
      Similarly, the response to bradykinin was also inhibited by Pb. Protein kinase C
      did not play a role since the protein kinase C inhibitor GF 109203X did not
      reverse the effects of Pb. Interestingly, MDCK cells treated with Pb at
      concentrations above 1 microM, for periods of 5-20 min, displayed elevated levels
      of inositol 1,4,5-trisphosphate. In conclusion, Pb inhibits mobilization of Cai
      after agonist stimulation by a mechanism that is unrelated to the type of agonist
      used. Evidence is presented suggesting that the inhibition is due to increases in
      levels of inositol 1,4,5-trisphosphate, which possibly decreases the amount of
      Cai available for mobilization.

PMID- 12062926
TI  - A comparison of Haber's rule at different ages using a physiologically based
      pharmacokinetic (PBPK) model for chloroform in rats.
AB  - Haber's rule as commonly interpreted in inhalation toxicology, can be stated as
      exposure concentration times duration equals a constant biological effect, or C x
      t=k. In other words, identical products of concentration and duration lead to the
      same effect. The goals of this paper are to develop a biological and
      pharmacokinetic modeling approach for chloroform, and to evaluate Haber's rule
      for different ages by taking into account the physiological changes due to growth
      and aging in rats. Three-dimensional dose-response surfaces for liver toxicity
      were generated for each age group of interest: adolescent, adult, and senescent
      rats. The three-dimensional surfaces were then characterized with a generalized
      description of Haber's rule for each age group. The simulations suggest that
      adolescent rats need higher exposure levels in order to achieve similar levels of
      liver damage compared to adults or senescent rats, if the comparison is made
      using the same exposure length. In summary, a pharmacokinetic modeling approach
      with a biological framework including the chemical's mode of action, was used to
      relate concentration, exposure duration and effect. Major advantages of this
      approach include: the potential ability to extrapolate to humans, the inclusion
      of aging in the simulations, and the ability to summarize the results using a
      generalized form of Haber's rule.

PMID- 12062927
TI  - Evidence for the involvement of CYP1A2 in the metabolism of bromodichloromethane
      in rat liver.
AB  - Bromodichloromethane (BDCM) is a drinking water disinfectant by-product that has
      been implicated in liver, kidney and intestinal cancers in rodents and in
      intestinal tumors and low birth weight effects in humans. BDCM is also
      hepatotoxic and requires metabolic activation for both toxicity and
      carcinogenicity. We have recently reported that CYP1A2 may participate in that
      metabolism and we now report experiments to support that implication. Induction
      of CYP1A2 in male F344 rats without inducing CYP2E1 or CYP2B1/2, using TCDD,
      increased the hepatotoxicity of BDCM when compared to earlier work conducted
      under similar protocols. Inhibition of CYP1A2, with isosafrole, reduced the
      metabolism and toxicity of BDCM in the previously induced rats. In addition,
      specific activities and Western blots for these CYP isoenzymes were measured 24 h
      after exposure. Activity data show that only CYP1A2 was inhibited by isosafrole;
      isosafrole forms a complex with CYP1A2 that persists for more than 24 h. Western
      blot results generally agree with the activity data except that isosafrole
      induced the protein for all isoenzymes measured. A physiologically based
      pharmacokinetic model, developed previously, estimated that BDCM metabolism was
      complete about 7 h after gavage dosing. It is noteworthy that the reduction in
      CYP1A2 activity was still measurable despite the production of additional CYP1A2
      protein during the period of approximately 18 h after BDCM metabolism was
      complete. These results demonstrate that CYP1A2 does metabolize BDCM and does
      contribute to hepatotoxicity under certain conditions.

PMID- 12062928
TI  - Neither forced running nor forced swimming affect acute pyridostigmine toxicity
      or brain-regional cholinesterase inhibition in rats.
AB  - Stress-induced change in the distribution of the drug pyridostigmine (PYR) has
      been proposed as a contributing factor to unexplained illnesses in Persian Gulf
      War veterans. We evaluated the effects of two stress models, forced running and
      forced swimming, on acute PYR (30 mg/kg, p.o.) toxicity and cholinesterase (ChE)
      inhibition in the blood and selected brain regions of young adult male Sprague
      Dawley rats (6 weeks of age). Plasma corticosterone levels were measured at 0, 1
      and 3 h after termination of forced swimming or forced running to confirm the
      induction of stress. PYR was given either immediately before stress (15 min
      swimming; 20 min running) or immediately after stress (15 min swimming; 90 min
      running) and cholinergic toxicity and ChE inhibition were evaluated at 1, 2 or 4
      h after PYR exposure. Additionally, rats were subjected to either swimming (15
      min) or running (90 min) stress, anesthetized, injected with horseradish
      peroxidase (HRP, 100 mg/kg, transcardial) and brain-regional HRP activity
      measured as an indicator of altered blood-brain barrier integrity. Both forced
      swimming and forced running resulted in significant elevations of plasma
      corticosterone levels. PYR caused cholinergic toxicity at all time-points
      evaluated. Swimming and running stress had little influence on expression of PYR
      induced toxicity, however. Blood ChE activity was generally inhibited 77-91% at 1
      4 h after PYR, but rats pretreated with PYR prior to forced swimming showed
      lesser inhibition (64%) 1 h after dosing, possibly because of swimming-induced
      hypothermia and delayed absorption of the drug. Minimal changes in ChE activity
      were noted in frontal cortex, cerebellum and hippocampus following PYR exposure
      (maximal inhibition 28%), and neither swimming nor running stress affected the
      degree of inhibition. Neither stress model increased HRP accumulation in any
      brain region. The results suggest that stress associated with forced running or
      forced swimming has little effect on acute PYR toxicity, entry of PYR into the
      brain or PYR-induced brain-regional ChE inhibition.

PMID- 12062929
TI  - Quantitative structure--activity relationships for inducers of cytochromes P450
      and nuclear receptor ligands involved in P450 regulation within the CYP1, CYP2,
      CYP3 and CYP4 families.
AB  - The results of quantitative structure-activity relationships (QSARs) are reported
      for several series of cytochrome P450 inducers, including those which also act as
      ligands for the various nuclear receptors involved in regulation of the relevant
      P450 genes, namely, CYP1, CYP2, CYP3 and CYP4. In several examples presented, the
      QSARs are consistent with homology modelling studies of the nuclear receptor
      ligand-binding domains (LBDs) based on available crystal structures of the
      oestrogen and peroxisome proliferator-activated receptors' LBDs. Good
      correlations (R=0.91-0.99) are found between various structural parameters and
      biological activity (either in the form of P450 induction or ligand-binding
      affinity) for the Ah receptor (AhR), human estrogen receptor alpha (hER alpha),
      human glucocorticoid receptor (hGR) and the rat peroxisome proliferator-activated
      receptor alpha (rPPAR alpha).

PMID- 12062930
TI  - Pb and Cd poisoning during development alters cerebellar and striatal function in
      rats.
AB  - The present study was designed to examine more fully the neurochemical and
      behavioral interactions that derive from continued lead and cadmium poisoning in
      pups, whose mothers were exposed via drinking water (300 mg/l of Pb and 10 mg/l
      of Cd) throughout pregnancy and lactation. At weaning, these metals produced an
      increase in DOPAC, 5-HT and 5-HIAA contents in cerebellum, but the monoamine
      contents in striatum remained unaltered. The cerebral energetic metabolism was
      modified by the Cd-Pb exposition only in striatum. On the other hand, the Na+/K+
      ATPase activity was inhibited significantly in both regions at PN21, whereas the
      alkaline phosphatase activity was not affected by the treatment. The intoxicated
      animals showed a short-term normocitic anemia, but revealed long-term alterations
      in the motor activity in open-field, where they showed an increase in both
      ambulating and rearing. So, it can be concluded that perinatal exposure to lead
      and cadmium provoke neurochemical alterations in cerebellum and striatum that can
      be related with the changes in motor activity observed in the adulthood.

PMID- 12062931
TI  - Effect of methoxychlor on the antioxidant system in mitochondrial and microsome
      rich fractions of rat testis.
AB  - Methoxychlor, an environmental contaminant, which is widely used as a pesticide
      in many countries, has been shown to induce reproductive abnormalities in male
      rats. The precise nature and mechanism of action of methoxychlor on the male
      reproductive system is not clear. In the present study, we have sought to
      investigate the induction of oxidative stress in the testis of rat after exposure
      to methoxychlor. Methoxychlor (1, 10, and 100 mg kg(-1) body weight per day) was
      administered orally to the rats for 45 days. After 24 h of the last treatment the
      animals were killed using anesthetic ether. The body weight of the animals
      administered with methoxychlor did not show any significant change. The weights
      of the testis, epididymis, seminal vesicles and ventral prostate decreased
      significantly in 100 mg dose but remained unchanged in 1 and 10 mg doses.
      Mitochondrial and microsome-rich fractions of the testis were obtained by the
      method of differential centrifugation. The activities of antioxidant enzymes such
      as superoxide dismutase, catalase, glutathione reductase and glutathione
      peroxidase decreased significantly in the animals treated with methoxychlor in a
      dose-dependent manner in the mitochondrial and microsome-rich fractions of rat
      testis. The levels of hydrogen peroxide generation (H(2)O(2)) and lipid
      peroxidation increased in mitochondrial and microsome-rich fractions of the
      testis of the rats treated with methoxychlor. The results suggested that the low
      to medium doses of methoxychlor elicit depletion of antioxidant enzymes and
      concomitant increase in the levels of H(2)O(2) and lipid peroxidation
      differentially in mitochondrial and microsome-rich fractions of rat testis. In
      conclusion, the adverse effect of methoxychlor on male reproduction could be due
      to the induction of oxidative stress in testis.

PMID- 12062932
TI  - Rate and capacity of hepatic microsomal ring-hydroxylation of phenol to
      hydroquinone and catechol in rainbow trout (Oncorhynchus mykiss).
AB  - Rainbow trout (Oncorhynchus mykiss) liver microsomes were used to study the rate
      of ring-hydroxylation of phenol at 11 and 25 degrees C by directly measuring the
      production of two potentially toxic metabolites, hydroquinone (HQ) and catechol
      (CAT). An HPLC method with integrated ultraviolet and electrochemical detection
      was used for metabolite identification and quantification at low (pmol) formation
      rates found in fish. The Michaelis-Menten saturation kinetics for the production
      of HQ and CAT over a range of phenol concentrations were determined at trout
      physiological pH. The apparent Km's for the production of HQ and CAT at 11
      degrees C were 14+/-1 and 10+/-1 mM, respectively, with Vmax's of 552+/-71 and
      161+/-15 pmol/min per mg protein. The kinetic parameters for HQ and CAT at 25
      degrees C were 22+/-1 and 32+/-3 mM (Km) and 1752+/-175 and 940+/-73 pmol/min per
      mg protein (Vmax), respectively. The calculated increase in metabolic rate per 10
      degrees C temperature rise (Q(10)) was 2.28 for HQ and 3.53 for CAT production.
      These experiments assess the potential for metabolic bioactivation in fish
      through direct quantification of putative reactive metabolites at the low, but
      toxicologically significant, chemical concentrations found in aquatic organisms.
      This work initiates a series of studies to compare activation pathway, rate, and
      capacity across fish species, providing a basis for development of biologically
      based dose response models in diverse species.

PMID- 12062933
TI  - Troglitazone enhances the hepatotoxicity of acetaminophen by inducing CYP3A in
      rats.
AB  - Troglitazone (TRZ) is the first of a new group of oral antidiabetic drugs, the
      thiazolidinediones, and is proven to lower plasma glucose levels in patients with
      type 2 diabetes mellitus. However, the concern has been raised because of several
      reports, in which severe hepatic dysfunction leading to hepatic failure was
      demonstrated in a few patients receiving the drug. We studied the effects of TRZ
      on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP)
      in rats, both of which exert their toxic effects through bioactivation associated
      with cytochrome P450 3A (CYP3A) and 2E1 (CYP2E1). Male standard (Wistar/ST) and
      type 2 diabetic model (GK/Jal) rats were kept on a powdered chow diet containing
      0, 100, 500 mg/kg/rat of TRZ. Three weeks later, the rats were either sacrificed
      for an in vitro metabolism study or challenged with 0.50 g/kg CCl(4) p.o. or 0.75
      g/kg APAP i.p.TRZ at 100 and 500 mg/kg/rat increased the CYP3A level as well as
      the testosterone 6beta-hydroxylation activities in liver microsomes, but did not
      affect CYP2E1. TRZ also enhanced APAP hepatotoxicity, as evidenced by
      significantly increased levels of alanine aminotransferase, aspartate
      aminotransferase and alpha-glutathione S-transferase in the plasma of rats, and
      by significantly low hepatic glutathione concentration. Our study demonstrated
      that high doses of TRZ can enhance hepatotoxicity of APAP in Wistar/ST and GK/Jal
      by inducing hepatic CYP3A.

PMID- 12062934
TI  - Changes of serum alpha 2u-globulin in the subacute oral toxicity study of ethynyl
      estradiol and bisphenol A based on the draft protocol for the 'Enhanced OECD Test
      Guideline No. 407'.
AB  - To investigate the usefulness of serum alpha 2u-globulin changes as a new
      parameter for detecting endocrine-mediated effects, we performed a 28-day
      repeated-dose toxicity study using the administration of bisphenol A (BPA) or
      ethynyl estradiol (EE) in male rats, based on the draft protocol of the 'Enhanced
      OECD Test Guideline 407 (enhanced TG 407)'. BPA at doses of 0, 40, 200 and 1000
      mg/kg per day or EE at doses of 0, 15, 75 and 375 microg/kg per day were orally
      administered to SD rats. The highest dose of BPA was reduced to 600 mg/kg per day
      from the second week of the study onwards because a male rat given 1000 mg/kg per
      day of BPA died within the first week, showing toxic clinical signs. In the assay
      using BPA, a reduction in the level of alpha 2u-globulin was detected in the
      group receiving a dose of 600 mg/kg per day. Reductions in the absolute and
      relative ventral prostate weights were only observed in the 600 mg/kg per day
      group. In the assay using EE, the alpha 2u-globulin level decreased significantly
      in the 375 microg/kg per day group. A reduction in the absolute and relative
      dorsolateral prostate weights was also observed in the 75 and 375 microg/kg per
      day groups, morphologically abnormal sperm were observed in the 375 microg/kg per
      day group. Furthermore, atrophic changes in the prostate and seminal vesicle and
      degenerative changes in the testis were observed in the 375 microg/kg per day
      group. Although the alpha 2u-globulin level was reduced in this assay using BPA
      and EE, further studies are necessary before this assay becomes a useful method
      for detecting endocrine-mediated effects.

PMID- 12062935
TI  - Methylmercury inhibits nitric oxide production mediated by Ca(2+) overload and
      protein kinase A activation.
AB  - The importance of cytosolic free calcium level intracellular Ca(2+), [Ca(2+)]i,
      in neutrophil activation prompted us to investigate changes in [Ca(2+)]i of
      neutrophils caused by methylmercury (MeHg), which has been shown to have
      immunomodulatory properties. We have shown in this paper that MeHg increased
      [Ca(2+)]i in the mouse peritoneal neutrophil. The L-type calcium channel blocker
      verapamil can decrease the elevated [Ca(2+)]i caused by 10 microM MeHg,
      suggesting that Ca(2+)-influx through L-type Ca(2+) channel mediates the effect
      of MeHg. Moreover, MeHg potently decreased nitric oxide (NO) production but also
      the protein and mRNA level of NO synthase induced by lipopolysaccharide. Both
      verapamil (1 microM) and H-89 (10 microM) can antagonize the inhibitory effect of
      MeHg (10 microM) on NO production. These findings lead us to conclude that MeHg
      inhibits NO production mediated at least in part by Ca(2+)-activated adenylate
      cyclase-cAMP-protein kinase A pathway.

PMID- 12062936
TI  - Determination of the sensitising activity of the rubber contact sensitisers TMTD,
      ZDMC, MBT and DEA in a modified local lymph node assay and the effect of sodium
      dodecyl sulfate pretreatment on local lymph node responses.
AB  - A modified local lymph node assay (LLNA) was used to determine the sensitising
      activity of four chemicals used for the production of natural rubber latex
      products. Tetramethylthiuramdisulfide (TMTD), 2-mercaptobenzothiazole (MBT) and
      zincdimethyldithiocarbamate (ZDMC), three moderate human sensitisers, and
      diethylamine (DEA) a known human sensitiser, were epicutaneously administered on
      the ear and the proliferating activity in the draining (auricular) lymph node
      (LN) was determined by ex vivo (3)H-thymidine incorporation. Consistent results
      were obtained for TMTD and ZDMC with stimulation indices (SI) above 3,
      identifying these compounds as sensitiser, while for DEA and MBT inconsistent
      results were obtained. For all parameters determined such as LN weight, LN cell
      number, cell proliferation per 2 x 10(6) cells, and cell proliferation per LN
      statistical significant increases were observed. The SI, expressed as cellular
      proliferation per LN or per animal (left and right LN combined), was the most
      sensitive parameter with an optimum at day 5 after start of
      treatment.Furthermore, we investigated whether the use of sodium dodecyl sulfate
      (SDS) was able to enhance weak responses in the LLNA. SDS treatment with dosages
      of 10% and higher resulted in a SI above 3, while a dosage of 1% SDS showed no
      activity. Pretreatment with 1% SDS 1 h before application of the rubber chemicals
      enhanced the responses to these chemicals consistently, identifying also DEA and
      MBT as sensitisers. Our results indicate that SDS had synergistic activity on the
      LN responses of the administered rubber chemicals in the LLNA. For the moderately
      responding sensitisers TMTD and ZDMC both IFN-gamma and IL-4 production was
      observed. For the weakly responding sensitisers DEA and MBT both IFN-gamma and IL
      4 cytokine production was only observed after pretreatment of the animals with
      10% SDS. For 10% and 20% SDS, inducing approximately a SI of 20 in the LLNA, no
      induction of cytokines was observed.

PMID- 12062937
TI  - Enhanced oxidative stress in the skin of vitamin E deficient mice exposed to
      semisynthetic metal working fluids.
AB  - Metal working fluids (MWFs) are widely used in industry for metal cutting,
      drilling, shaping, lubricating, and milling. Many occupational health concerns
      have arisen for workers exposed to MWFs. It has been reported earlier that
      occupational exposure to MWFs causes allergic and irritant contact dermatitis.
      Previously, we have shown that dermal exposure of female and male B6C3F1 mice to
      5% MWFs for 3 months resulted in accumulation of mast cells and elevation of
      histamine in the skin. Topical exposure to MWFs also resulted in elevated
      oxidative stress in the liver of both sexes and the testes in males. The goal of
      this study was to evaluate whether preexisting oxidative stress in the skin
      exacerbated mast cell influx after MWFs treatment. Oxidative stress in the skin
      of B6C3F1 mice was generated by dietary vitamin E deprivation. Mice were given
      vitamin E deficient (5-10 i.v./kg of vitamin E) or basal (50 i.v./kg of vitamin
      E) diets for 34 weeks. Topical treatment with MWFs (100 microl, 30%) started
      after 18 weeks of alimentary vitamin E deprivation. Histology of the skin after
      16 weeks of exposure to MWFs revealed a 53% increase in mast cell accumulation in
      vitamin E deficient diets compared to mice given a vitamin E sufficient diet.
      Total antioxidant reserve in skin of vitamin E deprived mice treated with MWFs
      was decreased by 66% as compared to those mice given a vitamin E sufficient diet.
      GSH and protein thiols in the dermis of vitamin E deprived mice exposed to MWFs
      were also decreased 39 and 42%, respectively, as compared to mice given basal
      diet. This study clearly delineates the role of oxidative stress in enhancing
      mast cell accumulation caused by topical exposure to MWFs.

PMID- 12062938
TI  - Indices of antioxidant status in rats subjected to wood smoke inhalation and/or
      thermal injury.
AB  - The present study investigated antioxidant status in lavage fluid, lung, liver,
      heart and kidney in a rat model to simulate an inhalation injury as might be
      encountered by firefighters and burn victims. Anesthetized rats received either a
      20% total body surface area (TBSA) full thickness scald or a sham burn. After a 5
      h recovery period, half of the animals in the burn or sham burn groups were
      exposed to cooled western bark (fir and pine) smoke for 16.25 min. The remaining
      rats in each group breathed room air. At 1, 12, 24, 48 and 96 h after exposure to
      the smoke, five rats from each of the four groups were euthanatized and lungs
      were lavaged by infusing three 5 ml aliquots of normal saline for evaluation of
      airway cellular content and lung wet to dry weight ratios to estimate lung water
      content. A second series of five rats/group per time point were euthanatized at
      the above times and lung, liver, kidney and heart were removed for evaluation of
      tissue antioxidant enzyme activities and for thiobarbituric acid reactive
      substances (TBARS) concentrations, as well as for lung histology. Smoke exposure
      resulted in average plasma carboxyhemoglobin (COHb) of 19+/-2% in the two smoke
      exposed groups and produced areas of erosion of the tracheal surface, resulting
      in loss of epithelium and exposed basement membrane. Lung water content was not
      significantly different among the four groups during the 96-h experimental
      period. Lung TBARS levels were 2-3-fold higher at 12 h in smoke exposed rats
      compared with controls. These levels peaked at 24 h and remained significantly
      elevated at 48 h compared to controls. TBARS were also elevated in liver, but not
      in heart or kidney in response to burn or combined injury. Minor effects on lung
      antioxidant enzyme activities were observed after smoke inhalation. These data
      suggest that smoke inhalation, independent of burn injury, induces an oxidant
      stress that persists for at least the first 48 h after smoke exposure.

PMID- 12062939
TI  - Simultaneous screening and detection of drugs in small blood samples and
      bloodstains.
AB  - A gas chromatography-mass spectrometry (GC-MS) method is described for the
      screening and detection of morphine, codeine, cocaine, benzoylecgonine,
      methylecgonine, cocaethylene, delta-9-tetrahydrocannabinol (THC), 11-nor-9
      carboxy-THC (THC-COOH), 11-hydroxy-THC (11-OH-THC), amphetamine, methamphetamine,
      3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymetamphetamine (MDMA) and
      N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in small blood samples
      and bloodstains using solid phase SPE columns and a pipetting robot (Gilson Aspec
      XL). The detection limits are in the order of 1.62-4.10 ng/50 microl spot
      (amphetamines), 0.15-0.82 ng/50 microl spot (cannabinoids), 1.67-4.70 ng/50
      microl spot (cocaine and derivatives) and 4.53-4.91 ng/50 microl spot (opiates)
      and the correlation factors are between 0.9957 and 0.9999. The method has proven
      useful in forensic cases with only small sample volumes or bloodstains.

PMID- 12062940
TI  - Estimating age of humans based on telomere shortening.
AB  - To estimate age using DNA based on telomere shortening, we determined the
      terminal restriction fragment (TRF) length, as telomere length, using Southern
      blot analysis of peripheral human blood and blood stains. All blood stains had
      been stored at room temperature for 5 months. The average TRF length clearly
      showed a tendency to shortening with aging. The formula for age estimation was
      based on a correlation between average TRF length and age of the subjects. The
      estimated age calculated from TRF length widely depends on environmental and
      genetic factors. However, as long as the DNA is well preserved, use of our method
      is feasible regardless of age of the subject and can give a rough estimation of
      age of subjects in forensic samples that carry no morphological information.

PMID- 12062941
TI  - Somatic mutations at STR loci--a reason for three-allele pattern and mosaicism.
AB  - Two families are analysed in which one of the parents exhibited a three-allele
      pattern at the ACTBP2 locus. Since the alleles were obviously segregated
      independently to the children, a generalised mosaicism must be assumed involving
      at least two tissues in one of them and at least four tissues in the other one.
      The intensity of the PCR amplified alleles in both three-allele individuals
      indicate an occurrence in a very early embryonic stage. Occurrence was most
      probably due to a single step mutation in both cases. Forensic implications would
      include paternity testing as well as stain analysis.

PMID- 12062942
TI  - Fatal alcohol poisoning: medico-legal practices and mortality statistics.
AB  - Compilation of mortality statistics from death certificate data is based on
      international and national conventions which in certain situations result in the
      underlying cause-of-death other than that established and reported by the
      physician. The present study compares all fatal alcohol poisonings in 1997 as
      registered on forensic toxicological grounds at the accredited central laboratory
      and as presented in the national cause-of-death statistics, according to the
      underlying cause-of-death, by applying international statistical rules and
      principles in ICD-10. Four groups were formed, and case frequencies in each group
      were obtained from forensic toxicological data, group "T51" for acute poisonings
      due to alcohol alone, and group "Comb" for acute alcohol poisonings combined with
      some drug, medicament or other biological substance, and from cause-of-death
      statistics data, group "X45", for deaths from alcohol poisoning, and group "F102"
      for those medico-legal fatal alcohol poisoning deaths which at the statistics
      office were inferred to be due to alcoholism. The study shows that in Finland the
      officially compiled statistics on fatal alcohol poisonings, when compared with
      medico-legal statements based on forensic toxicological examinations, were
      underrepresented by 31.4% in 1997. About two-thirds of this underrepresentation
      is explained by preferring, as the underlying cause-of-death, alcoholism to acute
      alcohol poisoning, and about one-third by preferring, in cases of acute combined
      poisonings, the drug component to the alcohol. From 1998 onwards, more emphasis
      has been put on the alcohol component when coding medico-legally proven
      accidental deaths from simultaneous poisoning with alcohol and a medicinal agent.
      This change in coding practices presumably explains the subsequent decline in the
      annual underrepresentation rate of alcohol poisoning in mortality statistics to
      the level of 15-16%. It is concluded that the present ICD rules inevitably lead
      to underrepresentation of alcohol poisonings in the mortality statistics, and
      conceptual and practical proposals for future procedures are made.

PMID- 12062943
TI  - Electrocution--autopsy study with emphasis on "electrical petechiae".
AB  - Fatalities caused by electrocution (n = 37) were re-examined on the basis of the
      autopsy records, the police reports and the technical expertise. Accidents
      including two lightning deaths caused 2/3rd and suicides 1/4th of the fatalities
      and there were two homicides. Carelessness or ignorance were a major reason for
      accidental deaths while technical defects could be verified in five cases only.
      Low-voltage ac and male victims predominated. Electrical burns or current marks
      were detected in 81% including all high voltage electrocutions. The seven victims
      lacking burns were electrocuted in a wet environment including six cases of
      suicide in the bathtub with a hair drier. Petechial haemorrhages were present in
      74% of the cases and the favourite sites were the skin of the eyelids,
      conjunctivae, visceral pleura, and the epicard. The presence of petechiae did not
      depend on the voltage or the current pathway relative to the heart. It is,
      therefore, suggested that the petechiae are not caused by asphyxia but by a
      combination of venous congestion due to cardiac arrest and a sudden rise in blood
      pressure induced by muscle contractions. Consequently, "electrical petechiae"
      represent a non-specific but typical finding in electrocution irrespective of the
      mechanism leading to death. Unlike electrical burns, petechiae also indicate the
      vital origin of the events. The relevance of this typical morphological sign in
      the examination of possible electrocution fatalities is therefore emphasised.

PMID- 12062944
TI  - Hemorrhages of the tongue in the postmortem diagnostics of strangulation.
AB  - Hemorrhages of the tongue can be useful for the diagnosis in cases of lethal neck
      compression. The reported frequencies of tongue bleedings in the literature in
      cases of suicidal hanging range from 0 to 14% and in homicidal strangulation
      (str.) from 5 to 37%. This study gives a summary of the incidence and intensity
      of tongue bleedings in cases of homicidal str. by ligature, manual str., suicidal
      str. by ligature and suicidal hanging. In 25% of all homicides significant or
      massive hemorrhages of the tongue were detected. In contrast to this, in suicidal
      hanging the tongue was unaffected in 95%. The causes of massive hemorrhages here
      (2%) could be explained by an "abnormal" position of the loop.

PMID- 12062945
TI  - Non-destructive dental-age calculation methods in adults: intra- and inter
      observer effects.
AB  - The aim of the present study was to obtain data on the reliability and
      reproducibility of two non-destructive dental-age estimation methods in adults by
      calculating inter- and intra-observer effects. Both a morphological and a
      radiological technique available in the scientific literature were evaluated on a
      number of recently extracted teeth: the morphological technique was evaluated on
      a total of 160 teeth by two examiners, while three examiners applied the
      radiological technique on apical radiographs of 72 extracted teeth. Paired t
      tests were used to calculate intra- and inter-observer differences. For the
      morphological method, both examiners were able to produce dental-age estimations
      that did not differ significantly from the real age of the teeth, obtaining a
      mean error between 0.5 and 1.8 years and a standard deviation of this error
      between 9.0 and 11.3 years. When using the radiological technique according to
      the original protocol, all three examiners produced age estimations that were
      statistically comparable to the real age of the teeth with a mean error of 0.5
      2.5 years and a standard deviation of 4.6-9.8 years. For both techniques, intra
      observer differences were observed. Based on the results of this study, it can be
      concluded that both non-destructive dental-age estimation techniques were able to
      produce reasonably accurate dental-age estimations, at least when these
      techniques were applied appropriately. However, the forensic odontologist is
      recommended to use different age estimation techniques and perform repetitive
      measurements in order to verify the reproducibility of the calculations
      performed.

PMID- 12062946
TI  - Sexual dimorphism in teeth: discriminatory effectiveness of permanent lower
      canine size observed in a XVIIIth century osteological series.
AB  - Recent studies have shown that the most dimorphic tooth is the mandibular canine.
      We have carried out a study on a random sample of 146 skeletons dating from the
      plague outbreak in Marseilles (1722). We studied 1284 maxillary and 1432
      mandibular permanent teeth. Sexual dimorphism was tested on 89 individuals. We
      selected a set of four dental indices and calculated the dimorphism percentage by
      ratio expression male/female. Dimorphic ranking was made, by allotting the first
      rank to the tooth presenting the highest dimorphism and the last rank to the one
      presenting the lowest ratio. Comparisons of means were made on both sexes (sex
      determined by post-cranial data) through a Student's test (t-test). We noted that
      lower canines and lateral incisor are the most interesting teeth in the dimorphic
      dental determination. The lower index presented the highest relative risk with RR
      = 1.56 [1.04-2.32]. In 58% of the cases, the lower dental index enabled a correct
      sex determination (determined on the basis of the post-cranial skeleton). These
      results showed the existence of a relative dental dimorphism (male > female
      mesiodistal diameters) with humans. In conclusion, this method, using dental
      measurements, may be used as an additional technique to determine sex on
      fragmentary adult skeletons, immature material, missing pieces or ambiguities on
      post-cranial remains.

PMID- 12062948
TI  - Fatal pedestrian-bicycle collisions.
AB  - Although, fatal collisions between pedestrians and bicycles are relatively rare,
      they are still of forensic relevance because of the need to explore the
      circumstances of the accident. Based on three reconstructed cases, situation and
      injury patterns are presented that might prove useful in future cases: usually
      the person causing the accident is the cyclist while the pedestrian generally
      suffers more severe injuries; the situation at the site of accident is important
      for its reconstruction: end location of the persons involved in the accident,
      injuries and traces on pedestrians and cyclists, traces at the site of accident
      and on the bicycle; because of the lack of pre-crash traces and any eyewitness
      accounts, the pedestrian's injuries are the best starting point for the
      reconstruction of the accident; a characteristic wound on the lower leg of the
      pedestrian that reveals the initial impact between the front wheel and the leg is
      crucial not because of its seriousness, but because of its external morphology;
      the injuries that can be expected by the following impact between body and
      handlebar are unspecific and only minor; the most severe injuries to the
      pedestrian as a result of the accident are caused secondarily by falling and
      hitting the head on the road; the fall of the cyclist, however, corresponds to a
      throw-off followed by a sliding phase with less impact load when the head hits
      the ground [maximum abbreviated injury scale 1 (MAIS 1)]; the cyclists involved
      are mainly younger persons on fashionable bicycles (here: mountain bikes); in the
      great majority of cases, the injured pedestrians are frail, elderly people with a
      lower tolerance of trauma.

PMID- 12062947
TI  - Comparison of the variables affecting the recovery of DNA from common drinking
      containers.
AB  - As the boundaries of forensic DNA profiling continue to expand, less obvious
      sources of biological evidence are being collected at crime scenes for DNA
      profiling. One example is the recovery of biological evidence from common drink
      containers, such as bottles and cans, which have been found at crime scenes.
      There are many variables that may have an impact on recovering a DNA profile from
      such exhibits. In this research, the effects of person to person variation, time,
      type of drink (including alcoholic and non-alcoholic beverages), and type of
      drink container, were assessed for their impact on the major analytical outcomes
      of the DNA process. The results show that the alpha-amylase activity varies from
      individual to individual and is reduced in the presence of some alcoholic drinks.
      A reasonable DNA yield was obtained from all samples, however, the concentrations
      exhibited significant person to person variation. The type of drink container
      influenced the DNA yield with cans giving a higher yield than bottles of the same
      drink type. To a reduced extent the presence or absence of alcohol affected the
      overall DNA yield and when partial or failed DNA profiles were produced they were
      more likely to be associated with alcoholic drinks than non-alcoholic drinks.

PMID- 12062949
TI  - Molecular analysis of the human esterase D gene ESD(*)Q0(yonago) responsible for
      incompatibility in a Japanese paternity case.
AB  - In a Japanese paternity test, an alleged father was excluded only by reverse
      homozygosity of esterase D (ESD) phenotypes (mother, ESD 1; child, ESD 1; alleged
      father, ESD 2) out of 43 classical and DNA markers investigated. To solve the
      aberrant inheritance of the ESD phenotypes observed between them, fragments for
      all eight coding exons amplified by polymerase chain reaction (PCR) were
      subjected to DNA analysis. The child and alleged father shared a null allele,
      originating from ESD(*)1. It was characterized by having TGA for the stop codon
      instead of TCA for serine at codon 63. Thus, the sharing of a rare null gene,
      ESD(*)Q0(yonago), increased the probability of paternity.

PMID- 12062950
TI  - A framework for risk assessment and decision-making strategies in dangerous good
      transportation.
AB  - The risk from dangerous goods transport by road and strategies for selecting road
      load/routes are faced in this paper, by developing an original site-oriented
      framework of general applicability at local level. A realistic evaluation of the
      frequency must take into account on one side inherent factors (e.g. tunnels, rail
      bridges, bend radii, slope, characteristics of neighborhood, etc.) on the other
      side factors correlated to the traffic conditions (e.g. dangerous goods trucks,
      etc.). Field data were collected on the selected highway, by systematic
      investigation, providing input data for a database reporting tendencies and
      intrinsic parameter/site-oriented statistics. The developed technique was applied
      to a pilot area, considering both the individual risk and societal risk and
      making reference to flammable and explosive scenarios. In this way, a risk
      assessment, sensitive to route features and population exposed, is proposed, so
      that the overall uncertainties in risk analysis can be lowered.

PMID- 12062951
TI  - Safety, health or the environment--which comes first?
AB  - This paper describes the development and application of two integrated models
      which can be used for assessing the life cycle risk (to life) and environmental
      impact of a number of possible concept options for new offshore oil and gas
      developments. The two models can also be used for ranking the designs in terms of
      lowest human risk and environmental impact. The paper also gives values/criteria
      for both risks to safety, health and the environment by which the total safety,
      health and environmental assessment/impact may be balanced as a whole. The paper
      illustrates the use of the models and shows that the pragmatic or cosmetic
      improvement to safety, health or the environment may not be advantageous to the
      overall safety, health and environmental objectives. While the models were
      developed originally for offshore installations, the basic framework can be
      readily adapted for use on onshore petrochemical processes.

PMID- 12062953
TI  - Good and bad examples of siting and building biosafety level 4 laboratories: a
      study of Winnipeg, Galveston and Etobicoke.
AB  - The purpose of this paper is to evaluate successful and unsuccessful examples of
      siting and building biosafety level 4 (BSL-4) facilities in North America. The
      paper shows that well thought-out risk communication strategies, that are
      proactive in nature, are needed to counteract both public trust and negative
      media amplification. The paper suggests that such strategies, which combine
      communication tools including media briefings, public fora, focus groups, tours
      of the proposed facility, open and frequent communication with the public as much
      as possible do work.

PMID- 12062952
TI  - Technological disasters, crisis management and leadership stress.
AB  - This paper discusses how psychological stress disturbs decision making during
      technological crisis and disaster, and how to prevent this from happening. This
      is exemplified by scientific studies of a Norwegian large scale accident
      involving hazardous material, and of handling the far-off effects of the nuclear
      disaster at Chernobyl. The former constitutes an operative level of crisis
      management, whereas the latter involves crisis management at the strategic and
      political level. We conclude that stress had a negative effect on decision making
      in both cases.

PMID- 12062954
TI  - Loss of containment: experimental aerosol rain-out assessment.
AB  - We measured the temperature profiles and rain-out spatial distribution for
      flashing water jets generated from a pilot scale experimental setup. This allowed
      us to define the transitions between three types of jets (stable, mechanically
      fragmented, flashing). The present experimental data when compared to other
      authors' data show that the transition to flashing type occurs at lower superheat
      when the orifice length increases, and that homogeneous aerosol behavior could be
      a valid assumption for mechanically fragmented jets whereas it is not for
      flashing jets.

PMID- 12062955
TI  - Investment appraisal using quantitative risk analysis.
AB  - Investment appraisal concerned with investments in fire safety systems is
      discussed. Particular attention is directed at evaluating, in terms of the
      Bayesian decision theory, the risk reduction that investment in a fire safety
      system involves. It is shown how the monetary value of the change from a building
      design without any specific fire protection system to one including such a system
      can be estimated by use of quantitative risk analysis, the results of which are
      expressed in terms of a Risk-adjusted net present value. This represents the
      intrinsic monetary value of investing in the fire safety system. The method
      suggested is exemplified by a case study performed in an Avesta Sheffield
      factory.

PMID- 12062956
TI  - The relation of cool flames and auto-ignition phenomena to process safety at
      elevated pressure and temperature.
AB  - The cool-flame phenomenon can occur in fuel-oxygen (air) mixtures within the
      flammable range and outside the flammable range, at fuel-rich compositions, at
      temperatures below the auto-ignition temperature (AIT). It is caused by chemical
      reactions occurring spontaneously at relatively low temperatures and is favoured
      by elevated pressure. The hazards that cool flames generate are described. These
      vary from spoiling a product specification through contamination and explosive
      decomposition of condensed peroxides to the appearance of unexpected normal (hot)
      flame (two-stage ignition).

PMID- 12062957
TI  - Theoretical and experimental investigation into the explosive boiling potential
      of thermally stratified liquid-liquid systems.
AB  - The occurrence of a rapid phase transition, or so-called explosive boiling, when
      a cold volatile liquid comes into contact with a hot liquid or hot surface is a
      potential hazard in industry. This study was focused on the explosive boiling
      potential of thermally stratified liquid-liquid systems that result from a
      runaway reaction. The experimental runs were performed on both a non-reacting and
      a reacting system. The experimental results showed that under the analysed
      conditions, the cold phase was superheated but did not evaporate explosively, as
      the limits of superheat of the phase were not achieved. The response of the cold
      phase appeared to be completely controlled by the interface temperature between
      the hot and the cold phase. In general, based on the order of magnitude of
      temperature differences that result from a runaway reaction in a multi-phasic
      system and the fact that the system is pressurised by its own vapour pressure,
      the occurrence of explosive boiling under runaway conditions appears unlikely for
      these type of systems.

PMID- 12062959
TI  - Autocatalytic decomposition reactions, hazards and detection.
AB  - In the chemical industry, estimation methods based on dynamic Differential
      Scanning Calorimetry (DSC) measurements have been developed for a preliminary
      screening of the risk associated to a chemical operation. An important point for
      the assessment of thermal risk is the identification of autocatalytic reactions.
      These types of reactions require our special attention and should be clearly
      distinguished from nth order reactions. Until today, the most reliable tool for
      the identification of autocatalytic decompositions was an isothermal DSC
      measurement. A new screening method based on dynamic DSC measurements for the
      identification of autocatalytic decompositions has been developed. The method
      consists of fitting a first order kinetic model to the measured heat release rate
      curve (from dynamic DSC measurement) and determining the apparent activation
      energy. If the apparent activation energy is higher than 220 kJ/mol, the
      decomposition is autocatalytic. By taking into account the cases with the border
      value of the apparent activation energy (180-220 kJ/mol), as well as the
      exception to this method, it should be possible to apply our new screening tool
      to about 80% of the cases.

PMID- 12062958
TI  - Auto-ignition hazard of mixtures of ammonia, hydrogen, methane and air in a urea
      plant.
AB  - The auto-ignition of NH(3)/CH(4)/H(2)/air mixtures constitutes a hazard that is
      of much concern in urea plants. In this study, the auto-ignition behaviour of
      NH(3)/CH(4)/H(2)/air mixtures is investigated experimentally for pressures up to
      7500 kPa. The experiments were carried out in a closed spherical vessel with a
      volume of 8 dm(3). The concentration and the pressure dependence of the auto
      ignition temperature (AIT) were determined for four types of mixtures: NH(3)/air,
      NH(3)/CH(4)/air, NH(3)/H(2)/air and NH(3)/CH(4)/H(2)/air. The most ignitable
      NH(3)/air mixtures were situated between stoichiometry and the upper flammability
      limit. Small amounts of methane and hydrogen decrease the AIT of NH(3)/air
      mixtures to a large extent. The pressure dependence of the AIT could be
      correlated by a Semenov relationship. For the multi-fuel mixtures, a distinct
      deviation from the Semenov correlation was observed at the lowest temperatures.
      With respect to the explosion hazard in urea plants, the experimental results
      were used to assess realistic AIT values in the pool reactor and the ammonia
      scrubber, operating at a pressure of 15,000 kPa.

PMID- 12062960
TI  - How is it possible? Why didn't we do anything? A case history!
AB  - Two similar serious accidents occurred at a metal refining process installation
      within a 6-month time interval. The first one killed ten people, and the second
      accident one person. The accidents provide a typical case history of how a safety
      management system and a corresponding organisation could have prevented the
      occurrence of such an accident or, at least, have reduced its effects. The case
      is also interesting because it illustrates the physico-chemical complexities
      forming the root cause of the accidents.

PMID- 12062962
TI  - Predicting full-length transcripts.

PMID- 12062964
TI  - Using lobster noses to inspire robot sensor design.
AB  - Robots are needed to locate the sources of toxic chemical plumes. Lobsters, which
      track odor plumes for many ecologically crucial activities, can provide
      inspiration for robot designers. Before accurate search strategies for robots can
      be developed, how odor molecules are captured by the lobster's chemosensors must
      be understood. A recent study by Koehl et al. shows how lobster olfactory
      antennules alter the patterns of concentration in turbulent odor plumes during
      odor sampling.

PMID- 12062965
TI  - Nanostructures as tailored biological probes.
AB  - A new generation of spectroscopic dyes is gradually becoming available to
      biological researchers, from an unexpected source: materials chemists who study
      the synthesis and properties of nano-sized inorganic objects. Research into
      tailoring the optical properties, surface chemistry and biocompatibility of
      metallic and semiconductor nanoparticles, exemplified in part by a recent report
      by Mirkin, Schatz and coworkers, is fulfilling the promise of these
      nanostructures as customizable substitutes for organic molecular probes.

PMID- 12062966
TI  - Towards quantitative assays with peptide chips: a surface engineering approach.
AB  - The development of peptide and protein microarrays has created enormous
      opportunities in biomedical research. Current chip-based assays are well suited
      for identifying candidate protein or enzyme activities but still require
      conventional solution phase experiments to validate hits. Here, three surface
      engineering strategies for microarray design are described and are illustrated in
      the development of a peptide chip for the quantitative analysis of kinase
      activity on solid support. These strategies promise to widen the application of
      microarrays by permitting the evaluation of hits in a chip-based format.

PMID- 12062971
TI  - GM foods in Spanish newspapers.

PMID- 12062972
TI  - The evolution of the biotechnology industry in Germany.
AB  - In the past five years, the climate for commercial biotechnology in Germany has
      improved significantly and has resulted in an increase in the number of
      biotechnology companies. On examination of the underlying factors of the
      evolution of the biotechnology industry in Germany, and against the background of
      the current situation, it is predicted that many German biotech companies will
      have to change their business models to focus on product development rather than
      on platform technologies.

PMID- 12062973
TI  - Where will the wood come from? Plantation forests and the role of biotechnology.
AB  - Wood is almost as important to humanity as food, and the natural forests from
      which most of it is harvested from are of enormous environmental value. However,
      these slow-growing forests are unable to meet current demand, resulting in the
      loss and degradation of forest. Plantation forests have the potential to supply
      the bulk of humanity's wood needs on a long-term basis, and so reduce to
      acceptable limits the harvest pressures on natural forests. However, if they are
      to be successful, plantation forests must have a far higher yield of timber than
      their natural counterparts, on much shorter rotation times. To achieve this in
      reasonable time, biotechnology must be applied to the tree-improvement process,
      for which large increases in public and private capital investment are needed.
      However, additional obstacles exist in the form of opposition to plantations,
      some forest ecocertification schemes, and concerns about aspects of forest
      biotechnology, especially genetic engineering. It is the intention of this
      article to explain, in detail, why plantation forests are needed to sustainably
      meet the world's demand for wood, why they are not being developed fast enough,
      and why the application of biotechnology to tree improvement is essential to
      speeding up this process.

PMID- 12062974
TI  - Bioterrorism: responding to an emerging threat.
AB  - Only a few years ago bioterrorism was considered a remote concern but few today
      are complacent about the possibility of biological agents being intentionally
      used to cause widespread panic, disruption, disease and death. By its very
      nature, the biological weapons threat - with its close links to naturally
      occurring infectious agents and disease - requires a different paradigm than that
      for conventional terrorism, military strikes or attacks caused by other weapons
      of mass destruction. This evolving threat presents the medical, public health and
      scientific communities (importantly including biotechnology) with a set of
      difficult and pressing challenges. This article provides a brief overview of the
      threat from biological weapons, the nature of a bioterrorist attack and some of
      the issues that need to be addressed if we are to make meaningful progress to
      prevent or contain this disturbing and potentially catastrophic danger.

PMID- 12062975
TI  - Biotechnological approaches for L-ascorbic acid production.
AB  - Over the past decade there has been increasing pressure to develop alternatives
      to the Reichstein process, a largely chemical synthesis by which the vast
      majority of world vitamin C (L-ascorbic acid, L-AA) is produced. The pressures
      include increasing environmental concerns and legislation, and the need to
      increase process efficiency and reduce capital costs. The development of
      efficient fermentation processes in the past ten years has also represented a
      catalyst for change. Here, we describe the development of biotechnological
      alternatives for the synthesis of Reichstein intermediates by industrial
      microorganisms. The recent elucidation of the plant biosynthetic pathway
      represents new opportunities not only for the direct synthesis of L-AA by
      fermentation but also for the production of human crop plants and animal fodder
      with enhanced nutritional value. We discuss the potential for these developments
      in the light of recent findings concerning L-AA biosynthesis in plants.

PMID- 12062977
TI  - Profile: Peter Ghazal interviewed by Suzanne Berry.

PMID- 12062976
TI  - Lessons from nature: stimuli-responsive polymers and their biomedical
      applications.
AB  - Response to stimulus is a basic process of living systems. Based on the lessons
      from nature, scientists have been designing useful materials that respond to
      external stimuli such as temperature, pH, light, electric field, chemicals and
      ionic strength. These responses are manifested as dramatic changes in one of the
      following: shape, surface characteristics, solubility, formation of an intricate
      molecular self-assembly or a sol-to-gel transition. Applications of stimuli
      responsive, or 'smart', polymers in delivery of therapeutics, tissue engineering,
      bioseparations, sensors or actuators have been studied extensively and numerous
      papers and patents are evidence of rapid progress in this area. Understanding the
      structure-property relationship is essential for the further development and
      rational design of new functional smart materials. For example, kinetic and
      thermodynamic control of the coil-to-globule transition could be achieved through
      changes in polymer composition and topology.

PMID- 12062978
TI  - And the winner is...

PMID- 12062979
TI  - Oral drug and old vaccine renew smallpox bioterror debate.

PMID- 12062980
TI  - Tracking down the culprit in river blindness.

PMID- 12062981
TI  - Edible vaccines tackle mucosal infections head on.

PMID- 12062982
TI  - Malaria numbers game.

PMID- 12062983
TI  - FDA panel rejects common cold treatment.

PMID- 12062985
TI  - Bloodsucking fly blamed for transmitting HIV.

PMID- 12062986
TI  - HIV-AIDS prevalence estimates: art or science?

PMID- 12062987
TI  - Study highlights variation in Lyme disease presentation.

PMID- 12062988
TI  - Cash boost for emerging diseases.

PMID- 12062990
TI  - War and gerbils compound Afghan leishmaniasis epidemic.

PMID- 12062991
TI  - Shifty drifter up to no good.

PMID- 12062992
TI  - Resistance and refugees in Pakistan: challenges ahead in tuberculosis control.

PMID- 12062993
TI  - Role of nitric oxide in HIV-1 infection: friend or foe?
AB  - Nitric oxide (NO) is an important biologically active molecule that plays a key
      part in host defence against bacteria, protozoa, and tumour cells. NO has
      antiviral effects against several DNA viruses, such as murine poxvirus, herpes
      simplex virus, and Epstein-Barr virus, and some RNA viruses, such as
      coxsackievirus. In several studies, in vitro and in vivo, overproduction of NO
      has been noted in the presence of HIV-1 infection. Furthermore, increased NO
      production may contribute directly to the pathogenesis of HIV-1-associated
      dementia. The mechanisms of virus infection mediated by NO may be related to:
      direct antiviral effects of NO; impairment of antiviral defence mediated by T
      helper-1 immune response by suppressing T-helper-1 functions; NO-induced
      cytotoxic effects by oxidative injury with cellular and organ dysfunctions; and
      NO-induced oxidative stress leading to rapid viral evolution with productions of
      drug-resistant and immunologically tolerant mutants. By contrast, there is some
      evidence of NO activity--directly, indirectly, or both--decreasing or blocking
      HIV-1 replication, through inhibition of viral enzymes, such as reverse
      transcriptase, protease, or cellular nuclear transcription factor (NF-kappa B)
      and long-terminal repeat-driven transcription. Therefore, although NO surely
      plays an important part in HIV-1 infection, that role is sometimes helpful and
      other times damaging to the host. Future challenges are to learn more about the
      beneficial and harmful effects of NO in HIV-1 infection, and how to selectively
      inhibit excessive NO production or to use NO-releasing drugs to decrease viral
      replication. This review discusses the role of NO in the pathogenesis of HIV-1
      infection, inasmuch as its role against HIV-1 is unequivocal in inhibiting or
      increasing viral replication.

PMID- 12062994
TI  - Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 1:
      epidemiology, environmental predispositions, clinical manifestations, and
      therapy.
AB  - Kaposi's sarcoma (KS) is a mesenchymal tumour involving blood and lymphatic
      vessels. Only recently has the pathogenesis of this extraordinary neoplasm been
      elucidated. Viral oncogenesis and cytokine-induced growth together with some
      state of immunocompromise represent important conditions for this tumour to
      develop. In 1994, a novel virus was discovered and termed human herpesvirus 8
      (HHV8), also known as Kaposi's sarcoma-associated herpes virus, which can be
      found in all types of KS, whether related to HIV or not. In the era of highly
      active antiretroviral therapy (HAART), the incidence of AIDS-KS has considerably
      declined, probably due to enhanced immune reconstitution and anti-HHV8-specific
      immune responses. If HAART is able to prevent spreading of KS, local therapy of
      KS may become an essential component of patient management. Part 1 of the review
      covers the epidemiology, environmental predispositions, clinical manifestations,
      and therapy of KS. Newer treatments such as pegylated liposomal anthracyclines
      and experimental strategies are discussed. We also present rationales and
      graduated treatment algorithms for local and systemic therapy in patients with KS
      to appropriately meet the challenges of this extraordinary neoplasm. Part 2, to
      be published next month, will summarise recent insights in the pathogenesis of KS
      and will discuss other HHV8-related diseases such as Castleman's disease and
      primary effusion lymphoma.

PMID- 12062995
TI  - Epidemiology of chronic hepatitis C virus infection in sub-Saharan Africa.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease in the world.
      The WHO estimates that 3% (170 million) of the world's population are chronically
      infected with HCV. Sub-Saharan Africa is of great interest because it is reported
      to have the highest HCV prevalence rate (5.3%), and a concurrent HIV epidemic. In
      our review of the published literature we found consistent evidence of high HCV
      prevalence in many countries of Africa. We estimate the overall prevalence of HCV
      in Sub-Saharan Africa is 3.0%. The central African region has the highest
      estimated prevalence of 6%, west Africa has an estimated prevalence of 2.4%, and
      southern and east Africa with the lowest estimated prevalence of 1.6%. Given low
      sexual transmission of HCV and infrequency of intravenous drug use in Sub-Saharan
      Africa, iatrogenic causes of HCV transmission need to be further evaluated.

PMID- 12062996
TI  - Does hepatitis C virus cause severe liver disease only in people who drink
      alcohol?
AB  - Hepatitis C virus (HCV) infects about 170 million people worldwide, and has been
      portrayed in the media as a silent killer, incorrectly implying that cirrhosis
      and hepatocellular carcinoma are the certain final outcomes of infection. Results
      of numerous population-based surveys indicate that chronic HCV infection is
      highly prevalent in elderly people who, in most instances, do not develop end
      stage liver disease. In individuals who do progress to cirrhosis and
      hepatocellular carcinoma alcohol plays a fundamental part, via mechanisms that
      result in increased viral replication, enhanced HCV quasispecies complexity,
      increased liver-cell death, suppression of immune responses, and iron overload.
      Although overlaps are present in the histological appearance of the liver in
      patients with hepatitis C who do and do not drink alcohol, histology could be of
      some help in revealing the role of alcohol in HCV disease progression even in
      people who deny drinking. Interventions and high-impact, continuous public-health
      campaigns are needed to persuade doctors and patients infected with HCV of the
      importance of abstaining from alcohol if risk of progression towards cirrhosis
      and hepatocellular carcinoma is to be reduced.

PMID- 12062997
TI  - Could a herpesvirus be the cause of Kawasaki disease?
AB  - Kawasaki disease (KD) is an acute vasculitis of early childhood, the cause of
      which remains unknown. Many lines of evidence suggest an infectious aetiology,
      which may-in association with host genetic factors-lead to the characteristic
      clinical presentation of this disease. Accumulating data including animal models
      and epidemiological and immunological studies, suggest that viruses have an
      important role in human vasculitic disease. Whereas many infectious agents
      including viruses have been postulated as possible causes of KD, no single agent
      has been shown definitely to be associated with this disease and the causative
      agent remains elusive. We hypothesise that a ubiquitous virus of the gamma
      herpesvirus family is the likely aetiological agent for KD in genetically
      susceptible individuals.

PMID- 12062998
TI  - Concurrent acute gouty and gonococcal arthritis.

PMID- 12062999
TI  - Crossing the tropic of cancer.

PMID- 12063001
TI  - The mystery MAP.

PMID- 12063003
TI  - Radiotherapy services in countries in transition: gross national income per
      capita as a significant factor.
AB  - BACKGROUND AND PURPOSE: The acquisition of radiotherapy by countries in
      transition (CITs) is an evolutionary process from having no resources whatsoever,
      to meeting the standards adopted by well-developed countries. The influence of
      the economic ability of a country to acquire and sustain this technology has
      intuitively been accepted as a major factor but has not before been subjected to
      analysis for a large group of countries. This information has been analysed to
      provide guidance to countries commencing and expanding radiotherapy services.
      MATERIAL AND METHODS: The number of linear accelerators and (60)Co megavoltage
      teletherapy machines in 72 CITs, those with gross national income per capita
      (GNI/cap)<$12000 per annum (pa) and a sample of 12 countries with GNI/cap>$12000
      pa were expressed as machines per million population (MEV/mil) and used as an
      index of the ability of the country to provide a service. This figure was related
      to GNI/cap. The average populations of 24 further countries without radiotherapy
      were compared with 21 countries with radiotherapy facilities having the same
      range of GNI/cap. RESULTS: The relationship log(10) MEV/mil=-2.90+0.85 log(10)
      GNI/cap was identified between the machines and income. Also verified was that
      small low income countries were less likely to have the technology than those
      with large populations. CONCLUSIONS: The increase in the number of teletherapy
      machines is closely linked to the GNI/cap of a country. Our sample of well
      developed countries failed to demonstrate a levelling off of equipment
      acquisition with income. In the lower income group, smaller countries were less
      likely to have radiotherapy services than those with large populations.

PMID- 12063002
TI  - The radiotherapeutic injury--a complex 'wound'.
AB  - Radiotherapeutic normal tissue injury can be viewed as two simultaneously ongoing
      and interacting processes. The first has many features in common with the healing
      of traumatic wounds. The second is a set of transient or permanent alterations of
      cellular and extracellular components within the irradiated volume. In contrast
      to physical trauma, fractionated radiation therapy produces a series of repeated
      insults to tissues that undergo significant changes during the course of
      radiotherapy. Normal tissue responses are also influenced by rate of dose
      accumulation and other factors that relate to the radiation therapy schedule.
      This article reviews the principles of organised normal tissue responses during
      and after radiation therapy, the effect of radiation therapy on these responses,
      as well as some of the mechanisms underlying the development of recognisable
      injury. Important clinical implications relevant to these processes are also
      discussed.

PMID- 12063004
TI  - Has 3-D conformal radiotherapy (3D CRT) improved the local tumour control for
      stage I non-small cell lung cancer?
AB  - AIMS AND BACKGROUND: The high local failure rates observed after radiotherapy in
      stage I non-small cell lung cancer (NSCLC) may be improved by the use of 3
      dimensional conformal radiotherapy (3D CRT). MATERIALS AND METHODS: The case
      records of 113 patients who were treated with curative 3D CRT between 1991 and
      1999 were analysed. No elective nodal irradiation was performed, and doses of
      60Gy or more, in once-daily fractions of between 2 and 3Gy, were prescribed.
      RESULTS: The median actuarial survival of patients was 20 months, with 1-, 3- and
      5-year survival of 71, 25 and 12%, respectively. Local disease progression was
      the cause of death in 30% of patients, and 22% patients died from distant
      metastases. Grade 2-3 acute radiation pneumonitis (SWOG) was observed in 6.2% of
      patients. The median actuarial local progression-free survival (LPFS) was 27
      months, with 85 and 43% of patients free from local progression at 1 and 3 years,
      respectively. Endobronchial tumour extension significantly influenced LPFS, both
      on univariate (P=0.023) and multivariate analysis (P=0.023). The median actuarial
      cause-specific survival (CSS) was 19 months, and the respective 1- and 3-year
      rates were 72 and 30%. Multivariate analysis showed T2 classification (P=0.017)
      and the presence of endobronchial tumour extension (P=0.029) to be adverse
      prognostic factors for CSS. On multivariate analysis, T-stage significantly
      correlated with distant failure (P=0.005). CONCLUSIONS: Local failure rates
      remain substantial despite the use of 3D CRT for stage I NSCLC. Additional
      improvements in local control can come about with the use of radiation dose
      escalation and approaches to address the problem of tumour mobility.

PMID- 12063005
TI  - Stereotactic single high dose irradiation of lung tumors under respiratory
      gating.
AB  - PURPOSE: To investigate the feasibility of a stereotactic single high dose
      irradiation of lung tumors under respiratory gating and the clinical response.
      METHODS AND MATERIALS: Twenty-three malignant lung tumors less than 40mm in
      diameter were treated by a single fractional irradiation. RESULTS AND DISCUSSION:
      Local regrowth was seen in three of ten tumors irradiated less than 30Gy, the
      minimal dose. Only one regrowth was observed in the tumors treated by 30Gy of
      with a follow up length of 3-24 months. Apparently 30Gy is able to control the
      lung tumors with a diameter less than 40mm.

PMID- 12063006
TI  - Optimizing radiation treatment plans for lung cancer using lung perfusion
      information.
AB  - PURPOSE: To study the impact of incorporation of lung perfusion information in
      the optimization of radical radiotherapy (RT) treatment plans for patients with
      medically inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS:
      The treatment plans for a virtual phantom and for five NSCLC patients with
      typical defects of pre-RT lung perfusion were optimized to minimize geometrically
      determined parameters as the mean lung dose (MLD), the lung volume receiving more
      than 20 Gy (V20), and the functional equivalent of the MLD, using perfusion
      weighted dose-volume histograms. For the patients the (perfusion-weighted)
      optimized plans were compared to the clinically applied treatment plans. RESULTS:
      The feasibility of perfusion-weighted optimization was demonstrated in the
      phantom. Using perfusion information resulted in an increase of the weights of
      those beams that were directed through the hypo-perfused lung regions both for
      the phantom and for the studied patients. The automatically optimized dose
      distributions were improved with respect to lung toxicity compared with the
      clinical treatment plans. For patients with one hypo-perfused hemi-thorax, the
      estimated gain in post-RT lung perfusion was 6% of the prescribed dose compared
      to the geometrically optimized plan. For patients with smaller perfusion defects,
      perfusion-weighted optimization resulted in the same plan as the geometrically
      optimized plan. CONCLUSION: Perfusion-weighted optimization resulted in
      clinically well applicable treatment plans, which cause less radiation damage to
      functioning lung for patients with large perfusion defects.

PMID- 12063007
TI  - Radiotherapy for early stages testicular seminoma: patterns of care study in
      Germany.
AB  - BACKGROUND AND PURPOSE: To evaluate compliance of radiotherapeutic departments
      with 1997 German consensus guidelines for staging and treatment of testicular
      cancer patients. MATERIAL AND METHODS: A questionnaire was mailed to all
      departments of radiotherapy in Germany as identified by the data-base of the
      German Society for Radiation Oncology (DEGRO). The questionnaire was analysed
      with particular respect to institutional characteristics, frequency of seminoma
      patients treated per year, treatment techniques, and institutional compliance
      with consensus guidelines. RESULTS: Fifty-six institutions (39%) returned the
      questionnaire, 46% of which fully complied with consensus guidelines concerning
      staging requirements. A minimum workup with computed tomography (CT) of abdomen
      and pelvis, X-ray or CT of the chest and tumour markers was mandatory in 87.5% of
      the departments. Compliance with the recommended treatment schedule was high in
      stage I with less than 5% major violations of recommended dose prescription or
      target volume definition. In stage IIA/B, however, 22.6 and 10.2% of the
      departments showed major deviations from either standardised treatment target
      volumes or total doses of irradiation, respectively. CONCLUSIONS: Compliance with
      consensus recommendations in German departments for radiotherapy is satisfactory
      in many institutions. However, major deviations from treatment guidelines were
      observed in stage II disease indicating the need for continuous improvement in
      the quality of testicular cancer patient management.

PMID- 12063008
TI  - A phase I study of fludarabine combined with radiotherapy in patients with
      intermediate to locally advanced head and neck squamous cell carcinoma.
AB  - BACKGROUND AND PURPOSE: Fludarabine, 9-beta-D-arabinofuranosyl-2-fluoroadenine,
      is an adenine nucleoside analogue that has significant activity in hematological
      malignancies and has shown promising activity in combination with radiation in
      preclinical solid tumor models. In this framework, we designed two phase I trials
      (one conducted at M.D. Anderson Cancer Center in Houston, and the other conducted
      in two Belgian hospitals) exploring concurrent fludarabine and radiotherapy in
      patients with intermediate to locally advanced head and neck squamous cell
      carcinomas (HNSCC). MATERIALS AND METHODS: Fludarabine was administered i.v.
      daily 3-4 h before the last 10 fractions of a standard radiation fractionation
      regimen (70 Gy in 7 weeks). The main objective of the trials was to determine the
      maximum tolerated dose (MTD) of fludarabine in this particular setting. Twenty
      eight patients with stage T2-T4, any N, M0 were included in the study.
      Fludarabine doses started at 7.5 mg/m(2) per day (3 mg/m(2) per day in Houston)
      and increased by steps of 2.5 mg/m(2) per day (3 mg/m(2) per day in Houston).
      RESULTS: The addition of fludarabine at increasing doses to radiation did not
      result in increased intensity or duration of skin (18% grade 3 dermatitis) or
      mucosal (60% grade 3 mucositis) radiotoxicity compared to what was expected for
      radiation alone. At a daily dose of 17.5 mg/m(2), two patients out of five (40%)
      developed a grade 4 neutropenia, of whom one developed a neutropenic fever. This
      dose was set as the MTD. All patients developed a fludarabine dose-dependant
      lymphocytopenia. The plasma F-ara-A concentration peaked after the 30-min
      infusion in a dose-dependent fashion and reached an average peak concentration of
      approximately 2 microM for doses of 15 mg/m(2) and higher. CONCLUSIONS: This
      study demonstrates that fludarabine can be safely administered concurrently with
      radiation at a daily dose of 15 mg/m(2) during the final 2 weeks of radiotherapy.
      A phase II trial will be required to establish the potential role of concurrent
      fludarabine and radiotherapy in the treatment of moderately to locally advanced
      HNSCC.

PMID- 12063009
TI  - De Gustibus: time scale of loss and recovery of tastes caused by radiotherapy.
AB  - PURPOSE: To quantify the prevalence and distress of taste loss at different
      intervals after radiotherapy (RT) for head and neck cancer. MATERIALS AND
      METHODS: In four different groups of head and neck cancer patients (73 patients
      in total), taste loss and distress due to taste loss were evaluated by taste
      acuity tests and taste questionnaires. Group 1 (n=17) was analyzed prior to RT.
      Groups 2 (n=17), 3 (n=17) and 4 (n=22) were at 2, 6 and 12-24 months after
      treatment, respectively. A cross-sectional analysis was performed between these
      four groups. RESULTS: Prior to initiation of RT (group 1), partial taste loss was
      observed in 35, 18 and 6% of patients for bitter, salt and sweet, respectively.
      At 2 months after RT (group 2), taste loss (partial or total) was seen in 88, 82,
      76 and 53% for bitter, salt, sweet and sour, respectively. At 6 months (group 3),
      partial taste loss was seen in 71, 65, 41 and 41% (bitter, salt, sweet, sour) and
      after 1-2 years (group 4) in 41, 50, 27 and 27% (bitter, salt, sweet, sour).
      Distress caused by taste loss was most frequent in group 2 (82%). CONCLUSIONS: In
      this study, loss of taste after RT was found to be most pronounced after 2
      months. Bitter and salt qualities were most impaired. Gradual recovery was seen
      during the first year after treatment. Partial taste loss still persisted 1-2
      years after treatment and was responsible for slight to moderate discomfort.

PMID- 12063010
TI  - Preservation of parotid function with uncomplicated conformal radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate (1) parotid function, (2) subjective
      xerostomia and (3) pattern of relapses after conformal parotid-sparing
      radiotherapy (RT) for head and neck cancer. (4) To study dose-response curves of
      parotid glands. MATERIAL AND METHODS: From September 1999 to November 2000, 39
      head and neck cancer patients requiring bilateral neck RT were treated with a
      fairly simple conformal RT technique (three-field set-up+anterior lower neck
      field; two opposed oblique boost fields). The contralateral parotid was spared.
      Parotid function was assessed by salivary gland scintigraphies performed before,
      early (median 4 weeks) and late (median 28 weeks) after RT. Xerostomia was
      monitored by visual analogue scales (VAS) and LENT SOMA scores. Location of
      locoregional recurrences was studied in relation to the radiation fields. A dose
      response curve of parotids was created using logistic regression. RESULTS: (1)
      Early after RT, on salivary gland scintigraphy, the mean loss of secretion
      function in the spared parotid was 67% and total in the non-spared. Late after
      RT, the mean loss remained 19% in the spared and total in the non-spared parotid.
      Normal excretion function was regained in 75% of the spared parotids. (2) Late
      after RT, 78% of patients had no, minimal or acceptable subjective xerostomia.
      (3) No recurrence was seen near the spared parotid (11/39 locoregional
      recurrences). (4) The dose-response curve of parotids showed that the mean
      parotid dose should preferentially be < or =20 Gy, to obtain a good chance (> or
      =70%) for preservation of its function on scintigraphy. CONCLUSIONS: An easy
      conformal parotid-sparing RT technique prevents moderate or severe subjective
      xerostomia in 78% of patients. In the spared parotids, nearly complete to
      complete recovery is obtained after 6-12 months.

PMID- 12063011
TI  - Variation in the manganese superoxide dismutase gene (SOD2) is not a major cause
      of radiotherapy complications in breast cancer patients.
AB  - BACKGROUND AND PURPOSE: Small proportions of patients receiving radiotherapy
      develop marked long-term radiation damage. It is thought that this is due, at
      least in part, to intrinsic differences in cellular radiosensitivity, but the
      underlying mechanism is unknown. Reactive oxygen species are involved in cellular
      radiation damage, hence inter-individual differences in free radical
      detoxification may be related to radiosensitivity. Within mitochondria manganese
      superoxide dismutase (MnSOD) provides a major defence against oxidative damage by
      reactive oxygen species. MnSOD has been linked to expression of malignant
      phenotype and apoptosis and polymorphic variation in the gene, SOD2 to risk of
      breast cancer. MATERIALS AND METHODS: Forty-one breast cancer patients developing
      marked changes in breast appearance after radiotherapy and 39 patients who showed
      no clinically detectable reaction after radiotherapy were analyzed for germline
      sequence variation in SOD2. RESULTS: The Ala-9Val polymorphism was detected, but
      no other sequence variants were detected in SOD2. Both alleles of the Ala-9Val
      polymorphism were equally distributed between the two patient groups.
      CONCLUSIONS: Sequence variation in SOD2 is not the major cause of radiotherapy
      complications in women with breast cancer.

PMID- 12063012
TI  - In vivo determination of extra-target doses received from serial tomotherapy.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to perform in-vivo
      measurements of extracranial doses received by patients undergoing serial
      tomotherapy of the head and neck. MATERIAL AND METHODS: Intensity modulated
      radiotherapy treatment (IMRT) plans were designed for nine patients using the
      CORVUS treatment planning system (NOMOS Corp.). These plans were delivered using
      a tertiary collimator dedicated for serial tomotherapy attached to a 10-MV linear
      accelerator. For each patient, one optically stimulated luminescence dosimeter
      (OSLD) was placed on the sternum and one on the lower abdomen. The OSLDs were
      then processed, thereby estimating the in vivo absorbed doses to the sternum and
      gonads as a function of distance from the treatment site. RESULTS: The OSLDs were
      shown to measure known doses to within 5%, thereby validating their accuracy for
      this dose and energy range. In the patient studies, the dose received by the
      OSLDs varied in direct proportion to the number of monitor units delivered and
      inversely with the distance from the target volume; the patient dose at a
      distance of 15 cm from the target is approximately 0.4% of the total monitor
      units delivered, and drops to below 0.1% of the total MUs at approximately 40 cm
      from the center of the target. The average sternal dose was 1353 mSv and the
      average abdominal dose was 327 mSv for an average prescribed dose of 60.1 Gy.
      This can be attributed, at least partially, to the inefficient treatment delivery
      that on average required 9.9 MU/0.01 Gy. CONCLUSIONS: While IMRT reduces the
      normal tissue volume in the high-dose region, it also increases the overall
      monitor units delivered, and hence the whole-body dose, when compared with
      conventional treatment delivery. As has been noted in existing literature, these
      increases in whole-body dose from radiotherapy delivery may increase the
      likelihood of a radiation-induced secondary malignancy. Therefore, it is
      important to assess the risk of secondary malignancies from IMRT delivery, and
      compare this relative risk against the potential benefits of decreased normal
      tissue complication probabilities.

PMID- 12063013
TI  - Quality control of the stereotactic radiosurgery procedure with the polymer-gel
      dosimetry.
AB  - PURPOSE: To assess the entire geometric and dosimetric (relative) uncertainties
      of the radiosurgery procedure with the Leksell gamma knife. MATERIALS AND
      METHODS: The entire Leksell gamma knife stereotactic radiosurgery treatment
      procedure was simulated with the use of a special water filled head phantom and
      polymer-gel dosimeter evaluated by nuclear magnetic resonance (NMR). A test
      vessel filled with the polymer-gel dosimeter was fixed in the head phantom. The
      phantom underwent stereotactic NMR imaging, treatment planning and then
      irradiation according to the treatment plan prepared exactly the same way as in
      the ordinary treatment procedure for a patient. The treatment plan was
      represented by one isocenter positioned approximately centrally in the head
      phantom. This procedure was subsequently repeated for all four collimators (4, 8,
      14, 18mm) used on the Leksell gamma knife. Evaluation of dosimeters was performed
      on a Siemens EXPERT 1T NMR scanner. Dose profiles in X, Y and Z axes through the
      ellipsoidal shaped dose distribution were obtained to compare experimental
      results from the irradiated phantom with the treatment planning system
      calculations. RESULTS: Reasonable agreement was observed between the treatment
      planning system calculations of relative dose distribution and the measured data.
      The maximum observed deviation in the spatial position between the center of the
      measured and calculated dose profiles was 0.6mm. The maximum observed difference
      in full width of half maximum between calculated and measured profiles was 1.2mm.
      CONCLUSIONS: The use of polymer-gel dosimetry for a verification of stereotactic
      procedures has some unique advantages that can be summarized as follows: the
      dosimeter itself is tissue equivalent, three-dimensional dose distributions can
      be measured and the dosimeter allows simulation of the patient's procedures
      without any limitations.

PMID- 12063014
TI  - Regarding "a treatment planning comparison of 3D conformal therapy, intensity
      modulated photon therapy and proton therapy for treatment of advanced head and
      neck tumours".

PMID- 12063017
TI  - Gene quantification using real-time quantitative PCR: an emerging technology hits
      the mainstream.
AB  - The recent flood of reports using real-time Q-PCR testifies to the transformation
      of this technology from an experimental tool into the scientific mainstream. Many
      of the applications of real-time Q-PCR include measuring mRNA expression levels,
      DNA copy number, transgene copy number and expression analysis, allelic
      discrimination, and measuring viral titers. The range of applications of real
      time Q-PCR is immense and has been fueled in part by the proliferation of lower
      cost instrumentation and reagents. Successful application of real-time Q-PCR is
      not trivial. However, this review will help guide the reader through the
      variables that can limit the usefulness of this technology. Careful consideration
      of the assay design, template preparation, and analytical methods are essential
      for accurate gene quantification.

PMID- 12063016
TI  - Partial boosting of prostate tumours: forward planned conformal radiotherapy vs.
      inverse planned intensity modulated radiotherapy?

PMID- 12063018
TI  - Hematologic consequences of exposure to ionizing radiation.
AB  - From the early 1900s, it has been known that ionizing radiation (IR) impairs
      hematopoiesis through a variety of mechanisms. IR exposure directly damages
      hematopoietic stem cells and alters the capacity of bone marrow stromal elements
      to support and/or maintain hematopoiesis in vivo and in vitro. Exposure to IR
      induces dose-dependent declines in circulating hematopoietic cells not only
      through reduced bone marrow production, but also by redistribution and apoptosis
      of mature formed elements of the blood. Recently, the importance of using
      lymphocyte depletion kinetics to provide a "crude" dose estimate has been
      emphasized, particularly in rapid assessment of large numbers of individuals who
      may be exposed to IR through acts of terrorism or by accident. A practical
      strategy to estimate radiation dose and triage victims based upon clinical
      symptomatology is presented. An explosion of knowledge has occurred regarding
      molecular and cellular pathways that trigger and mediate hematologic responses to
      IR. In addition to damaging DNA, IR alters gene expression and transcription, and
      interferes with intracellular and intercellular signaling pathways. The clinical
      expression of these disturbances may be the development of leukemia, the most
      significant hematologic complication of IR exposure among survivors of the atomic
      bomb detonations over Japan. Those at greatest risk for leukemia are individuals
      exposed during childhood. The association of leukemia with chronic, low-dose-rate
      exposure from nuclear power plant accidents and/or nuclear device testing has
      been more difficult to establish, due in part to lack of precision and
      sensitivity of methods to assess doses that approach background radiation dose.
      Nevertheless, multiple myeloma may be associated with chronic exposure,
      particularly in those exposed at older ages.

PMID- 12063019
TI  - Real-time polymerase chain reaction in multiple myeloma: quantitative analysis of
      tumor contamination of stem cell harvests.
AB  - OBJECTIVE: Autologous transplantation of bone marrow (BM) and peripheral blood
      progenitor cells (PBPC) is commonly used for treatment of multiple myeloma (MM).
      Although both stem cell sources harbor residual clonal cells, a quantitative
      evaluation of their level of tumor contamination (LTC) still needs to be
      performed through highly accurate and reproducible approaches. In this study, we
      used a validated real-time polymerase chain reaction (PCR) strategy to evaluate
      LTC of BM and PBPC samples obtained from MM patients. MATERIALS AND METHODS: The
      patients underwent two different mobilization courses (defined as early or late
      course) following two cycles of cyclophosphamide 5 g/m(2). LTC was evaluated by
      measuring the number of clonal immunoglobulin heavy-chain rearrangements followed
      by normalization of samples using the GAPDH gene. RESULTS: Overall, 26 PBPC and
      12 BM samples were analyzed. Main results are as follows. 1) PBPC harvests are
      less contaminated than BM samples taken immediately after each mobilization
      course (median difference 2.68 logs; range 1.7 to 4.6) (p < 0.0001). 2) LTC of
      PBPC harvests has only minimal variation among different leukaphereses performed
      during the same mobilization course (median difference 0.45 logs; range 0.22 to
      1.2). 3) No difference was observed among PBPC and BM samples obtained after the
      late mobilization course as compared to the early mobilization course (median
      reduction 0.21 logs; range -0.39 to 1.3) (p = 0.84). 4) In PBPC but not in BM
      samples, there is a clear overestimation of the percentage of plasma cells when
      flow cytometric evaluation of CD38(bright) cells is compared to real-time PCR
      results. This suggests that in PBPC, most CD38(bright) cells do not belong to the
      neoplastic clone. CONCLUSIONS: Real-time PCR using the IgH rearrangement proved
      an effective tool for monitoring LTC in stem cell harvests from MM patients. The
      smaller LTC of PBPC harvests supports the role of PBPC as stem cell rescue for MM
      patients compared to BM cells.

PMID- 12063020
TI  - Monoclonal antibody 9C4 recognizes epithelial cellular adhesion molecule, a cell
      surface antigen expressed in early steps of erythropoiesis.
AB  - OBJECTIVE: Monoclonal antibody (mAb) 9C4 detects a surface antigen expressed on
      immature erythroid progenitor cells and epithelial tumor cell lines. The aim of
      this study was to identify the recognized surface antigen and to analyze a
      potential role of this molecule in early steps of erythropoiesis. MATERIALS AND
      METHODS: A pituitary-derived retroviral cDNA library was used to generate viruses
      and infect NIH-3T3 fibroblasts. The transfected cells were stained with mAb 9C4;
      positive cells were sorted by FACS; and a clonal cell line binding mAb 9C4 was
      established. cDNA encoding the 9C4-binding protein was amplified by polymerase
      chain reaction and cloned. Reactivity of mAb 9C4 with human bone marrow (BM)
      cells was analyzed by flow cytometry. RESULTS: Sequence analysis of the isolated
      cDNA uncovered a 100% identity with the epithelial cellular adhesion molecule (Ep
      CAM). Two-color flow cytometric analysis revealed that almost 100% of Ep-CAM(+)
      BM cells coexpressed CD105, E-cadherin, and high levels of CD71. Fractions of Ep
      CAM(+) BM cells also were CD34(+) but lacked glycophorin A expression, suggesting
      that Ep-CAM(+) cells represent immature erythroid cells. Reverse transcriptase
      polymerase chain reaction analysis of BM mononuclear cells revealed that the
      9C4(+) erythroblast population but not the 9C4(-) fraction expressed Ep-CAM mRNA.
      Peripheral blood CD34(+) cells induced in vitro to differentiate into the
      erythroid lineage showed strong Ep-CAM expression on days 3 to 7 of culture. The
      addition of Ep-CAM-specific mAbs 9C4 or KS1/4 to the culture resulted in two- to
      three-fold up-regulation of Ep-CAM protein expression. CONCLUSION: mAb 9C4
      recognizes Ep-CAM, a molecule expressed in the early steps of erythropoiesis.

PMID- 12063022
TI  - Human megakaryocytes cultured in vitro accumulate serotonin but not meta
      iodobenzylguanidine whereas platelets concentrate both.
AB  - OBJECTIVE: Thrombocytopenia is the major toxicity of radio-iodinated meta
      iodobenzylguanidine (MIBG) therapy in patients with recurrent neuroblastoma. MIBG
      is taken up in platelets via the serotonin transporter. Given the delayed
      appearance and long duration of the thrombocytopenia, it seems likely that the
      precursor megakaryocytes are the primary targets of [131I]MIBG radiotoxicity.
      MATERIALS AND METHODS: We investigated MIBG and serotonin uptake in cultured
      human megakaryocytes grown in vitro from CD34(+) cells obtained from bone marrow.
      RESULTS: With radio-iodinated MIBG, cell-associated radioactivity was negligible,
      even after prolonged incubations for up to 16 hours. In contrast, after 4 or 16
      hours with 10(-8) M [3H]serotonin, 6% or 14% of the added substrate was
      accumulated in the megakaryocytes. This uptake approached saturation above 10(-7)
      M and was reduced greater than 90% by coincubation by imipramine. This indicates
      specific uptake, which was confirmed by fluvoxamine and citalopram. The serotonin
      reuptake inhibitors fluvoxamine (0.3 nM) and citalopram (1 nM) effectively
      reduced serotonin uptake to 44% +/- 3% and 30% +/- 9% of the controls,
      respectively. CONCLUSIONS: Megakaryocytes efficiently retain serotonin in storage
      granules, as concluded from the consistent reductive effect of tetrabenazine on
      uptake, retention, and localization (micro-autoradiographic) of serotonin. Thus,
      serotonin, but not MIBG, is taken up by cultured megakaryocytes.

PMID- 12063021
TI  - Optimization of recombinant human erythropoietin therapy after allogeneic
      hematopoietic stem cell transplantation.
AB  - OBJECTIVE: Allogeneic hematopoietic stem cell transplantation (HSCT) is
      associated with prolonged anemia caused by defective erythropoietin (Epo)
      production. We enrolled 34 recipients of an allogeneic HSCT in three consecutive
      trials to determine the optimal utilization of recombinant human erythropoietin
      (rhEpo) therapy in this setting. MATERIALS AND METHODS: In the first trial (n =
      7), rhEpo 1400 U/kg/week was given from day 1 until a hemoglobin (Hb) level of 10
      g/dL was achieved, for a maximum of 60 days. In the second trial, rhEpo 500
      U/kg/week was given to achieve Hb levels of 13 to 14 g/dL in 13 anemic patients
      with fatigue 56 to 1440 days after transplant. In the third trial, rhEpo was
      scheduled to start on day 35 in 14 patients at a dose of 500 U/kg/week with the
      aim of achieving Hb levels of 13 to 14 g/dL. RESULTS: In trial 1, erythroid
      recovery to 1% reticulocytes and red blood cell transfusion independence were
      faster, but the number of transfusions was not reduced compared to 10 controls.
      Responses were brisk in trial 2, with transfusion independence achieved after a
      median of 1 week in 12 of 13 patients, and 2-g Hb increments or Hb values of 11,
      12, and 13 g/dL after 6, 7, 10, and 10 weeks, respectively. Transfusions were
      significantly reduced in the first month of rhEpo therapy. In trial 3,
      transfusion independence was obtained after a median of 1 week in 13 of 14
      patients, and 2-g Hb increments or Hb values of 11, 12, and 13 g/dL after 3, 4,
      6, and 8 weeks, respectively. Transfusions rates were considerably reduced
      compared to the previous month in the same patients or compared to controls
      undergoing peripheral blood or marrow transplant without rhEpo. CONCLUSIONS:
      Anemia after allogeneic HSCT is exquisitely sensitive to rhEpo. The benefit is
      minimal when it is given early post-transplant, as used in all trials to date.
      However, the rate of major response is greater than 90% when rhEpo is started
      after day 35. These data provide the basis on which to conduct a prospective,
      randomized, placebo-controlled trial of rhEpo therapy after allogeneic HSCT.

PMID- 12063023
TI  - Evidence for two commonly deleted regions on mouse chromosome 2 in gamma ray
      induced acute myeloid leukemic cells.
AB  - OBJECTIVE: The objective of this study was to delineate a precise molecular map
      of the commonly deleted region (CDR) on mouse chr2 in radiation-induced mouse
      acute myeloid leukemic (AML) cells. MATERIALS AND METHODS: We used a PCR-based
      loss of heterozygosity (LOH) assay to map the chr2-CDR in AML cells isolated from
      F1 hybrid mice (BALB/cJ x CBA/CaJ) which developed AML following exposure to a
      single dose of 3 Gy of 137Cs gamma rays. A total of 30 polymorphic microsatellite
      markers, mapping within or close to chr2(D-E), were used under optimized PCR
      conditions that generate a single major band for each marker on a nondenaturing
      polyacrylamide gel. RESULTS: Detailed LOH mapping identified two distinct AML
      CDRs: one localized to a 4.6 centiMorgan (cM) interval between markers D2Mit272
      and D2Mit394; the other mapped to a 0.8 cM interval between markers D2Mit276 and
      D2Mit444. Both CDRs span the mouse chr2E region. CONCLUSION: The data present,
      for the first time, evidence for two distinctly noncontiguous CDRs on mouse chr2
      harboring gene(s) involved in AML development. These CDRs are orthologous to
      human chromosomes 11p11-13 and 15q11-15 that have been implicated in subsets of
      AML. This finding indicates the region of mouse chr2 that must be searched for
      candidate genes involved in radiation-induced AML.

PMID- 12063024
TI  - Potential roles of extracellular signal-regulated kinase but not p38 during
      myeloid differentiation of U937 cells stimulated by cytokines: augmentation of
      differentiation via prolonged activation of extracellular signal-regulated
      kinase.
AB  - OBJECTIVE: To clarify the signaling mechanism of human myeloid differentiation by
      hematopoietic growth factors and cytokines, we investigated the role of
      extracellular signal-regulated kinase (ERK) during the differentiation of human
      monoblastic U937 cells stimulated by granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and tumor necrosis factor (TNF). MATERIALS AND METHODS: Myeloid
      differentiation was evaluated by morphology, function (respiratory burst
      activity), and cell surface expression of adhesion molecule (CD11b), and
      activation of ERK and/or p38 was determined by Western blotting and/or in vitro
      kinase assay. Inhibition of the ERK pathway was performed using PD98059, a
      specific inhibitor of this pathway. RESULTS: U937 cells were induced to be
      differentiated by the combination of GM-CSF and TNF, but only minimally by either
      cytokine alone. Transient phosphorylation and activation of ERK was induced by
      both GM-CSF alone and combination of the two cytokines, whereas sustained
      phosphorylation and activation was induced only by the combination. In addition,
      PD98059, a specific inhibitor of ERK pathway, almost completely abolished this
      prolonged phosphorylation of ERK and completely blocked differentiation. In
      contrast, both TNF alone and cytokine combination equivalently phosphorylated p38
      in U937 cells, which was dissociated from differentiation, and a specific
      inhibitor of p38 (SB203580) did not inhibit differentiation. CONCLUSIONS: The
      results indicate potential roles of sustained activation of ERK but not of p38 in
      the signaling pathways for human myeloid differentiation in U937 cells
      synergistically stimulated by the two physiologic cytokines GM-CSF and TNF.

PMID- 12063025
TI  - Myeloid-lymphoid initiating cells (ML-IC) are highly enriched in the rhodamine-c
      kit(+)CD33(-)CD38(-) fraction of umbilical cord CD34(+) cells.
AB  - OBJECTIVE: The study of hematopoietic stem cells (HSC) is limited by lack of
      specific markers for HSC. Rhodamine 123 (Rho) is one of the substrates of P
      glycoprotein (Pgp), and the presence of active Pgp can be shown by the efflux of
      Rho. Rho can also be used to measure the mitochondrial transmembrane potential
      (energy state) of a cell. We reasoned that selection of hematopoietic progenitors
      using a combination of Rho efflux and phenotypic markers might be superior to use
      of phenotypic markers alone. MATERIALS AND METHODS: We used the myeloid-lymphoid
      initiating cell (ML-IC) assay as functional measure of primitive progenitors.
      Umbilical cord blood CD34(+)CD33(-)CD38(-), CD34(+)CD33(-)CD38(-)Rho(-), and
      CD34(+)CD33(-)CD38(-)Rho(-)c-kit(+) cells were sorted singly onto AFT024 feeders
      to assess their capacity to become ML-IC. RESULTS: The frequency of ML-IC in
      CD34(+)CD33(-)CD38(-)Rho(-) cells was significantly higher (15 +/- 0.4%) than
      that in CD34(+)CD33(-)CD38(-) cells (6.2 +/- 0.9%, p < 0.05). However, the
      frequency of long-term culture-initiating cells (LTC-IC) (17 +/- 3% vs 12 +/-
      1.5%) and natural killer culture-initiating cells (NK-IC) (25 +/- 3% vs 20 +/-
      4%) was similar in the two populations. Following the treatment of CD34(+)CD33(
      )CD38(-)Rho(-) cells with verapamil, which blocks Pgp function, no increase in ML
      IC was detected compared with CD34(+)CD33(-)CD38(-) cells (6 +/- 0.7%),
      suggesting that differences in the energy state, which is reflected by Rho
      staining after verapamil treatment, cannot be used as a criterion to identify
      human HSC. Further selection of CD34(+)CD33(-)CD38(-)Rho(-) cells based on
      expression of c-kit significantly increased the frequency of ML-IC, LTC-IC and NK
      IC by 1.75-, 1.3-, and 1.8-fold, respectively. CONCLUSION: Combining the function
      of Pgp and phenotypic features of hematopoietic progenitors enriches the
      frequency of cord blood ML-IC to greater than 25%. Use of such enriched
      populations will allow us to characterize the biological behavior of human HSC.

PMID- 12063027
TI  - Human embryonic-derived hematopoietic repopulating cells require distinct factors
      to sustain in vivo repopulating function.
AB  - OBJECTIVE: We have previously identified a novel circulating embryonic blood cell
      capable of pluripotent hematopoietic reconstitution, which may serve as a target
      for in utero stem cell therapy. Based on its unique biological properties and
      ontogenic origin, we aim to examine the ability to maintain and retrovirally
      transduce fetal blood (FB) reconstituting cells in ex vivo culture conditions
      previously optimized for pluripotent hematopoietic repopulating cells derived
      from later stages of human ontogeny. METHODS: FB cells were evaluated for
      proliferative potential, progenitor composition, and SCID-repopulating cell (SRC)
      capacity before and after 3 days of serum free (SF) ex vivo culture using the
      previously optimized growth factor conditions of SCF, Flt-3L, IL-3, IL-6, and G
      CSF (GF Mix), in comparison to cultures using GF Mix + oncostatin M (OSM), or SCF
      + Flt-3L. We further examined the ability to retrovirally transduce FB-SRC
      maintained in culture using SCF + Flt-3L alone. RESULTS: Circulating FB-SRC could
      not be maintained under GF Mix conditions previously shown to sustain CB (cord
      blood)-SRC. Ex vivo culture with SCF + Flt-3L reduced the proliferation of
      primitive FB cells lacking lineage commitment markers (Lin(-)), but expanded FB
      progenitors and sustained FB-SRC compared to culture with GF Mix with and without
      OSM. Using SCF + Flt-3L, FB-SRC capable of multilineage reconstitution were
      successfully transduced, suggesting that SCF and Flt-3L are necessary and
      sufficient for the survival and transduction of human hematopoietic repopulating
      cells of embryonic origin. CONCLUSION: Our study provides novel insights into the
      requirements of primitive FB reconstituting cells that are essential for
      developing in utero stem cell gene therapy protocols, and further illustrates the
      biological distinctiveness of FB-SRC compared to hematopoietic repopulating cells
      from other stages of human ontogeny.

PMID- 12063026
TI  - Homing and clonogenic outgrowth of CD34(+) peripheral blood stem cells: a role
      for L-selectin?
AB  - OBJECTIVE: After transplantation of hematopoietic stem cells, adhesion molecules
      play a major role in the multistep process of engraftment in which L-selectin is
      suggested to be of relevance. A positive correlation previously was found between
      the number of reinfused L-selectin(+) stem cells and platelet recovery. In the
      present study, we determined the role of L-selectin in different engraftment
      steps, i.e., adhesion to endothelial cells, migration, and clonogenic outgrowth
      by in vitro assays that closely mimic the in vivo situation. MATERIALS AND
      METHODS: Flow adhesion and migration experiments were performed using the human
      bone marrow endothelial cell line 4LHBMEC and isolated peripheral CD34(+) cells
      with or without blocking of L-selectin-ligand interaction. Various clonogenic
      assays, including serum-free colony-forming unit-megakaryocytes (CFU-MK) and
      burst-forming unit-megakaryocytes (BFU-MK), were performed with sorted L
      selectin(+)L-selectin(-) cells or in the presence of antibodies. RESULTS:
      Blocking of L-selectin on CD34(+) cells did not significantly affect rolling over
      and firm adhesion to 4LHBMEC. In addition, no role for L-selectin was found in
      transendothelial migration experiments. Finally, in clonogenic outgrowth of
      sorted or anti-L-selectin monoclonal antibody-incubated CD34(+) cells, no key
      role for L-selectin expression could be defined in BFU-MK and CFU-MK assays.
      CONCLUSION: Using in vitro assays for CD34(+) stem cell adhesion, migration, and
      clonogenic capacity, we were not able to define a major role for L-selectin.

PMID- 12063028
TI  - Donor stem cells home to marrow efficiently and contribute to short- and long
      term hematopoiesis after low-cell-dose unconditioned bone marrow transplantation.
AB  - OBJECTIVE: To study the homing of donor stem cells, their contribution to short-
      and long-term hematopoiesis, and their functional capacity in an unconditioned
      marrow transplant model using a clinically relevant low marrow cell dose.
      MATERIALS AND METHODS: A sex-mismatch model was used in which 20 x 10(6) male
      Balb/cByJ cells were infused into unconditioned female Balb/cByJ mice. Male donor
      cells were detected in blood and marrow by fluorescence in situ hybridization.
      Serial transplantation into irradiated secondary recipients was used to assay
      donor stem cells. Donor hematopoiesis was stimulated after transplant by treating
      recipients with either stem cell factor (SCF) or sublethal irradiation. RESULTS:
      Donor-derived male cells were detected in recipient blood (1.2-3.0%) and marrow
      (2.4-5.4%) for up to 27 weeks, indicating a contribution to short-term
      hematopoiesis. Male repopulating units approached theoretically expected values,
      suggesting that transplantation was efficient. Donor stem cell levels after
      serial transplantation were similar to results observed in primary recipients.
      Donor stem cell levels 24 hours after infusion (1.3 +/- 0.2% SE) were similar to
      levels at later time points, indicating that homing was efficient. Stimulation by
      either SCF or sublethal irradiation after transplant did not alter donor marrow
      chimerism, suggesting that donor stem cells responded to the stress similarly to
      endogenous cells. CONCLUSION: We conclude that in a clinically relevant low-cell
      dose unconditioned transplant model, stem cells home to the marrow efficiently,
      contribute to both short- and long-term hematopoiesis, and, once engrafted,
      respond to stress effectively. These findings provide a rationale for the use of
      genetically modified stem cells in clinical protocols that omit intensive
      conditioning.

PMID- 12063029
TI  - Ex vivo expanded cord blood cells provide rapid engraftment in fetal sheep but
      lack long-term engrafting potential.
AB  - OBJECTIVE: Cord blood (CB) products are becoming routinely used in unrelated
      allogeneic transplantation for smaller pediatric patients. Because of the low
      numbers of cells in CB compared to bone marrow or peripheral blood progenitor
      cells, their use is more limited in larger adults. Therefore, we developed ex
      vivo expansion conditions for CB and currently are transplanting ex vivo expanded
      CB products to patients receiving high-dose chemotherapy. As there is concern
      that ex vivo expansion may exhaust long-term engrafting cells, the current
      clinical protocols consist of both an expanded fraction and an unexpanded
      fraction. To determine the effect of expansion culture on long-term engrafting
      cells, we evaluated the short- and long-term engrafting potential of ex vivo
      expanded CB using a fetal sheep xenogeneic transplant model. MATERIAL AND
      METHODS: CD 34(+) cells were selected from CB products and cultured in a two-step
      procedure in the presence of stem cell factor, megakaryocyte growth and
      differentiation factor, and granulocyte colony-stimulating factor for 14 days.
      Starting cells (CD34(+) cells), and cultured cells (day 7 and day 14 cells) were
      transplanted in 60-day-old fetal sheep and evaluated at various time points post
      transplant for the presence of human cells. Long-term engrafting cells were
      assessed by serial passage into secondary and tertiary recipients. RESULTS: Day
      14 expanded CB cells provided more rapid engraftment than either the day 7
      expanded cells or the day 0 cells; however, this engraftment was transient, and
      no human cells were detectable at 16 months post transplant in the animals that
      received the day 14 expanded cells. Day 0 cells had engrafted animals at 2 months
      post transplant and both the day 0 and day 7 cells persisted to 16 months or
      longer. In the secondary animals, the day 0 and day 7 cells engrafted
      equivalently at 3 months post transplant; however, no secondary engraftment
      resulted from the day 14 cells. The levels of engraftment in secondary animals
      receiving day 7 cells decreased with time to barely detectable levels at 12
      months post transplant. CONCLUSIONS: Ex vivo expansion of CB CD34(+) cells under
      the conditions described results in the generation of increased mature cells and
      progenitors that are capable of more rapid engraftment in fetal sheep compared to
      unexpanded CB CD34(+) cells. The expanded cells engrafted primary sheep but
      lacked secondary and tertiary engrafting potential. These studies demonstrate
      that although ex vivo expanded cells may be able to provide rapid short-term
      engraftment, the long-term potential of expanded grafts may be compromised.
      Therefore, clinical protocols may require transplantation of two fractions of
      cells, an expanded CB graft to provide rapid short-term engraftment and an
      unmanipulated fraction of CB graft to provide stem cells for long-term
      engraftment.

PMID- 12063030
TI  - Alloreactivity following in utero transplantation of cytokine-stimulated
      hematopoietic stem cells: the role of recipient CD4(-) cells.
AB  - OBJECTIVE: We have previously reported immunity to donor antigens following in
      utero transplantation (IUT) of cytokine-stimulated allogeneic hematopoietic stem
      cells (sca(+)/lin(-)) (day 9 of gestation). Transplanted mice showed accelerated
      rejection of donor skin grafts and high anti-donor cytotoxic response, a finding
      not seen in the control mice. This was accompanied by an enhancement of Th1 over
      Th2 cytokine production and persistent donor microchimerism. In order to assess
      the role of the thymus in allograft rejection, prenatal transplants were
      performed under similar experimental conditions at a later gestational age, when
      the thymus is more developed (day 13). MATERIALS AND METHODS: Cytokine-stimulated
      stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF)-purified
      sca(+)/lin(-) cells of C57BL/6 (H-2b, 1E(+)) background were injected into MHC
      mismatched BALB/c (H-2d, 1E(-)) fetal mouse recipients at day 13 of gestation.
      Chimerism was determined by highly sensitive (0.001%) semiquantitative polymerase
      chain reaction (PCR). Mixed lymphocyte reaction (MLR) and cytotoxic T-cell assay
      (CTL) were used to evaluate tolerance vs immunity. Cytokine levels were
      quantified in MLR supernatants using ELISA assay. The percent of T cells was
      determined by flow cytometry (FACS) and CD4/CD8 ratio calculated. Postnatal
      boosts (transplants without conditioning) were performed at 6 months of age to
      enhance donor chimerism and test the degree of tolerance. RESULTS: When assayed
      at 4 months of age, donor-type cells were not detected in the spleen or in the
      peripheral blood of BALB/c mice inoculated with C57BL/6 sca(+)/lin(-) cells.
      Transplanted but not control animals demonstrated high anti-donor MLR but not CTL
      responses. The increase of MLR reactivity was correlated with high levels of IL
      2. Furthermore, transplanted mice showed higher resistance to postnatal boosts
      with allogeneic bone marrow (BM) cells, when compared to the control mice. The
      later resistance was accompanied by the expansion of host-type CD4 cells.
      CONCLUSION: These data demonstrate that transplantation of cytokine-stimulated
      sca(+)/lin(-) allogeneic cells at 13 days of fetal development leads to the
      allosensitization, characterized by an enhancement of MLR alloreactivity and by
      the rejection of postnatal boosts (transplants without conditioning). Host-type
      CD4 cells might play a central role in this rejection. These findings indicate
      that the late injection of allogeneic cells may result in the development of
      allosensitization with subsequent donor graft rejection. Precise conditions for
      the development of tolerance must be established before prenatal transplants in
      humans with conditions other than SCID can be done.

PMID- 12063031
TI  - MUC1 and sialoglycan expression associated with cytotoxic T lymphocyte
      infiltration in eyelid malignant tumors.
AB  - PURPOSE: To elucidate the relation between infiltrating cytotoxic T lymphocytes
      and the expression of MUC1 and sialoglycans in malignant eyelid tumors. METHODS:
      The distribution of MUC1, Maackia amurensis lectin-II (MAL-II)-recognized
      sialoglycan, and CD8-positive T lymphocytes was examined histochemically in 14
      patients with malignant eyelid tumors: three squamous cell carcinomas, six
      sebaceous gland carcinomas, and five basal cell carcinomas. The density of CD8
      positive cells was examined and correlated with MUC1 and sialoglycan expression.
      RESULTS: MUC1 was identified in squamous cell carcinoma and sebaceous gland
      carcinoma, but not in basal cell carcinoma. CD8-positive cells were more densely
      distributed in those squamous cell and sebaceous gland carcinoma cases that were
      more intense in MUC1 expression and weaker in MAL-II binding. Tumors with a
      strong expression of both MUC1 and MAL-II-bound sialoglycans showed few CD8
      positive cells. CONCLUSIONS: MUC1 with few sialoglycans is likely to induce an
      intense infiltration of CD8-positive cytotoxic T lymphocytes in eyelid cancers.

PMID- 12063032
TI  - Immunological characteristics of patients with vernal keratoconjunctivitis.
AB  - PURPOSE: Previously, we have reported that local excision and immunosuppressive
      treatment are useful in treating patients with very severe vernal
      keratoconjunctivitis (VKC). METHODS: We measured serum levels of immunoglobulins,
      cytokines, and interleukin-2 receptors (IL-2R) and the concentration of IL-4 in
      tears of 10 patients with severe VKC, and made a comparison with data from 10
      healthy controls. Brush cytology specimens were examined to determine the number
      of inflammatory cells and the human lymphocyte antigen (HLA)-DR expression in
      conjunctiva. RESULTS: The mean serum level of total immunoglobulin (Ig)E, but not
      IgG, was higher in severe VKC patients compared with healthy controls. Specific
      IgE positivity to housedust, dust mites, and cat antigens was observed in 60-80%
      of patients. The level of IL-4 and IL-2R in serum and IL-4 in tears before
      treatment was higher in patients with VKC compared with controls. Serum levels of
      IL-2 and interferon-gamma did not increase. Brush cytology specimens from
      patients expressed HLA-DR. CONCLUSIONS: These results suggest that VKC could be a
      combination of type I allergic disease and an inflammatory cell disease including
      activated T cells, especially Th2 cells. Therefore, the surgical removal of
      inflammatory cells combined with immunosuppressive therapy could be advocated as
      a method of treatment.

PMID- 12063033
TI  - Higher concentration of transforming growth factor-beta in aqueous humor of
      glaucomatous eyes and diabetic eyes.
AB  - PURPOSE: Diabetic retinopathy and glaucoma are the primary causes of acquired
      blindness. Cytokines including transforming growth factor (TGF)-beta may be
      involved in these diseases. We therefore collected aqueous humor samples from
      patients with glaucoma and/or diabetes who were undergoing surgery, and
      determined the concentration of TGF-beta. METHODS: Aqueous humor samples were
      collected from 80 patients (84 eyes), including 19 eyes with primary open-angle
      glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated
      with POAG. Twenty-five eyes with cataract served as controls. The concentration
      of TGF-beta1 or TGF-beta2 was measured by enzyme-linked immunosorbent assay.
      RESULTS: The concentration of TGF-beta1 was less than 0.1 pg/mL in all of the
      groups. In contrast to controls who had 1001.4 +/- 444.1 pg/mL, the concentration
      of total TGF-beta2 in the diabetes group was 1715.6 +/- 882.1 pg/mL, and that in
      the diabetes complicated with POAG group was 1692.9 +/- 361.9 pg/mL. These were
      significantly higher than that in controls. In contrast to the controls who had
      321.2 +/- 197.9 pg/mL, the concentration of mature TGF-beta2 with POAG was 822.5
      +/- 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 +/- 648.4
      pg/mL. These were significantly higher than that in the controls. The eyes with
      diabetes complicated with POAG also had a significantly higher concentration than
      the eyes with diabetes alone. CONCLUSION: Total TGF-beta2 and mature TGF-beta2 in
      high concentration may correlate with progression of POAG, diabetes, and diabetes
      complicated with POAG.

PMID- 12063034
TI  - Quantitative analyses of cytomegalovirus genome in aqueous humor of patients with
      cytomegalovirus retinitis.
AB  - PURPOSE: To investigate copy numbers of cytomegalovirus (CMV) in CMV retinitis
      patients during ganciclovir treatment using real-time polymerase chain reaction
      (PCR). METHODS: Thirteen aqueous humor samples obtained from 6 patients with
      clinically diagnosed CMV retinitis were analyzed. As controls, aqueous humor
      samples were obtained at the time of surgery from patients with senile cataracts.
      RESULTS: The CMV genome was detected in the range from 10(1) to 10(4)
      copies/microL of aqueous humor before antiviral treatment. The samples obtained
      from retinitis patients showing widespread retinal changes contained much higher
      copy numbers than those from patients with focal lesions. After treatment, the
      copy number decreased to one hundredth of that observed prior to treatment, but
      the CMV genome was detectable for 4 to 8 weeks after ganciclovir administration
      to 4 patients. CONCLUSION: These results revealed the correlation between the
      copy numbers of the CMV genome and the extent of the area affected by CMV
      retinitis before antiviral treatment, and the prolonged retention of CMV genome
      after antiviral treatment. Quantitation of the viral genome after the start of
      therapy will be of value in determining whether to continue or intensify the
      dosage of antiviral agents.

PMID- 12063035
TI  - Effects of aging on the first and second-order kernels of multifocal
      electroretinogram.
AB  - PURPOSE: To determine the effects of aging on the first and second-order kernels
      of the multifocal electroretinogram (ERG). METHODS: Multifocal ERGs were recorded
      from 52 healthy subjects (52 eyes) (0 >or= refractive error >or= -3.0 diopter).
      The ages of the subjects ranged from 12-76 years with a mean (+/-SD) of 44.0 +/-
      20.2 years. The Visual Evoked Response Imaging System was used. The effects of
      aging on the response densities and on the implicit times of the first positive
      wave (P1) of the first-order kernel, and of the second and third positive waves
      (P2 and P3) of the second-order kernel were analyzed for the different age
      groups. RESULTS: The response densities of the first-order kernel P1 and second
      order kernel P2 waves decreased significantly, and the implicit times of the
      second-order kernel P2, and P3 were significantly prolonged (P <.05) in subjects
      over 50 years of age. CONCLUSION: The results suggest that the age of the subject
      should be considered when evaluating retinal function using multifocal ERGs in
      basic and clinical studies.

PMID- 12063036
TI  - Role of vitronectin receptor-type integrins and osteopontin in ischemia-induced
      retinal neovascularization.
AB  - PURPOSE: It has been reported that vitronectin receptor-type integrins mediate
      vascular cell proliferation and migration. In this study, we investigated the
      expression of vitronectin receptor-type integrins and osteopontin in ischemia
      induced retinal neovascularization, and examined the role of osteopontin in
      angiogenesis as a ligand of vitronectin receptor-type integrins. METHODS: Retinal
      neovascularization was produced by exposing C57BL/6J mice to 75% oxygen from
      postnatal day (P) 7 to P12. Expression of vitronectin receptor-type integrins and
      osteopontin was assessed by Northern blot analysis, in situ hybridization, and
      immunofluorescence. The role of osteopontin in retinal angiogenesis was evaluated
      by tube formation assay using cultured bovine retinal microcapillary endothelial
      cells. RESULTS: In the murine model, integrin alpha(v) mRNA was increased from
      P14 with a 2.6-fold peak response observed on P19, when retinal
      neovascularization was remarkable. Indirect immunofluorescence for vitronectin
      receptor-type integrins revealed prominent expression of integrin
      alpha(v)beta3/beta5 in the neovascular endothelial cells. Osteopontin mRNA was
      increased from P14, with a 2.0-fold peak response observed on P19. In situ
      hybridization demonstrated localization of osteopontin mRNA in neovascular tufts.
      Vascular endothelial growth factor-induced tube formation (8.3 +/- 0.6 mm/field)
      was inhibited significantly by treatment with anti-osteopontin antibody (4.8 +/-
      0.7 mm/field, P <.001). CONCLUSIONS: These data suggest that increased expression
      of both vitronectin receptor-type integrins and osteopontin in ischemic retina
      contribute to vascular endothelial cell proliferation and to retinal vascular
      formation by promoting interaction between endothelial cells and extracellular
      matrix, which leads to retinal neovascularization.

PMID- 12063037
TI  - Accuracy of suture adjustment in adjustable strabismus surgery evaluated at the
      initial postoperative examination.
AB  - PURPOSE: To clarify the efficacy of sliding-noose type adjustable suture
      strabismus surgery, we evaluated the accuracy of suture adjustment based on data
      from the initial postoperative examination performed 1-4 weeks after the surgery.
      METHODS: Thirty-four patients with various types of strabismus participated [age
      range, 12-79 years; range of far deviation, 4-123 prism diopters (PD)]. Under sub
      Tenon anesthesia, a recession (with or without a resection or muscle
      transposition) was performed with an adjustable suture (Guyton's procedure), and
      the suture was adjusted 6-24 hours after surgery. RESULTS: Twenty-six (76%)
      patients required suture adjustment one to eight times. In 50% and 75% of our
      patients, the errors from individual target angle were within +/- 0.8 and +/- 2.0
      PD, respectively, whereas 2 (6%) patients with esotropia showed an
      undercorrection larger than 10 PD. The error distribution was almost the same
      throughout the range of preoperative deviation. CONCLUSION: By using an
      adjustable suture with a sliding noose, pinpoint alignment of the eyes can be
      achieved in more than half of the cases, at least in the early postoperative
      period.

PMID- 12063038
TI  - Characteristics of hyperacuity sensitivity in normal and cyclovertical deviation
      subjects.
AB  - PURPOSE: To compare the sensitivity of hyperacuity of patients with cyclovertical
      deviation with that of subjects with normal vision. METHODS: The sensitivity of
      hyperacuity was measured in 42 volunteers with normal vision and in 12 patients
      with cyclovertical deviation, using a newly developed computerized device that
      randomly presents two opposing targets at vertical or at horizontal directions on
      the cathode ray tube display. RESULTS: In subjects with normal vision, higher
      sensitivity was obtained when the targets were aligned in either a vertical or a
      horizontal direction. These highly sensitive ranges were defined as "the neutral
      zone of hyperacuity." An anisotropy of the sensitivity of hyperacuity was
      observed in these subjects, ie, better sensitivity was obtained when the
      displacement was away from the neutral zone, whereas worse sensitivity was
      obtained when the displacement was close to the neutral zones. In the patients
      with cyclovertical deviation, the sensitivity of hyperacuity was low around the
      neutral zones, which may confirm the dysfunction of the central nervous system.
      CONCLUSION: This analytical method may be useful to investigate the
      pathophysiology of patients with cyclovertical deviations.

PMID- 12063039
TI  - The change in ocular refractive components after cycloplegia in children.
AB  - PURPOSE: To study the change in ocular refractive components after cycloplegia in
      children. METHODS: Anterior chamber depth, lens thickness, vitreous chamber
      length, and ocular axial length were measured in 135 Chinese children (270 eyes)
      before and after cycloplegia. The corneal curvatures of 136 selected eyes were
      studied before and after cycloplegia with a computerized video keratoscope.
      RESULTS: Anterior chamber depth increased (P <.001) while both lens thickness and
      vitreous chamber length decreased (P <.001) significantly after cycloplegia
      regardless of the refractive state. However, axial length increased in hyperopic
      eyes (P =.027) but decreased in myopic eyes (P =.008) after cycloplegia. Mean
      corneal power of zones 3 mm (MD3, P =.009) and keratometer K1 readings increased
      (P =.025) in hyperopic eyes, while MD3 (P =.033), K1 (P =.039) and K2 (P =.003)
      readings decreased in myopic eyes significantly after cycloplegia. Similarly,
      mean corneal power of zones 5 mm and 7 mm in myopic eyes decreased dramatically
      (P <or=.001). In both hyperopic and myopic eyes, there was significant difference
      (P <.001) in the mean value of the upper and lower half of the vertical meridian,
      as well as the medial and lateral half of the horizontal meridian, respectively.
      CONCLUSIONS: Cycloplegia has a great influence on various refractive components
      in children. There is asymmetry of the corneal surface within the same horizontal
      or vertical meridian.

PMID- 12063040
TI  - Laser subepithelial keratomileusis for low to moderate myopia: 6-month follow-up.
AB  - PURPOSE: To examine the effectiveness, safety, and stability of laser
      subepithelial keratomileusis (LASEK), a modified photorefractive keratectomy for
      low to moderate myopia. METHODS: This study evaluated the results of LASEK in 48
      myopic patients (84 eyes) with a consecutive 6-month follow-up period.
      Preoperative myopia ranged from 3.25 to 7.00 diopters (D). Uncorrected and
      corrected visual acuity, manifest refraction, epithelial healing time,
      postoperative pain, subepithelial corneal haze, and complications were examined.
      RESULTS: Uncorrected visual acuity of 20/30 or better was achieved in 78.6% of
      eyes at 1 week and in 96.4% at 6 months after surgery. A mean refraction of
      within +/-0.50 D was measured in 42 eyes (50.0%) and +/-1.0 D in 79 eyes (94.0%)
      at 6 months. The epithelial healing time was 3.68 +/- 0.69 days (range, 3-6 days)
      and postoperative pain scores were 1.49 +/- 0.65. The subepithelial corneal haze
      scores were 0.56 +/- 0.34 and 0.16 +/- 0.25 at 1 and 6 months, respectively. As
      for complications, alcohol leakage during surgery occurred in 3 eyes, incomplete
      epithelial detachment in 3 eyes, contact lens intolerance in 5 eyes and steroid
      induced elevated intraocular pressure (>21 mm Hg) in 1 eye. CONCLUSIONS: LASEK is
      an effective and safe procedure for low to moderate myopia. It can be considered
      an alternate type of refractive surgery for correction of low to moderate myopia.

PMID- 12063041
TI  - Secondary amyloidosis in a corneal graft.
AB  - PURPOSE: To describe a case of secondary amyloidosis that occurred in a corneal
      graft. METHODS: A 30-year-old Japanese woman had opacities in the corneal graft
      in her right eye. Slit-lamp microscopy examination demonstrated nodular,
      subepithelial opacities in the graft. Results of a physical examination and her
      past medical history were unremarkable, except for a history of a penetrating
      keratoplasty for keratoconus at the age of 17. Since then, the patient had worn a
      hard contact lens for over 10 years. The specimen obtained by keratectomy was
      examined histologically. RESULTS: The histologic examination revealed hyaline,
      and amorphous materials stained with Congo red, which were dichroic under
      polarized light. Transmission electron microscopy showed the characteristic
      fibrillar pattern of amyloid. CONCLUSIONS: This appears to be the first reported
      case of secondary amyloidosis in a corneal graft. A long-standing history of hard
      contact lens wear may play a role in the pathogenesis of this rare condition.

PMID- 12063042
TI  - Multifocal electroretinogram in patients with central serous chorioretinopathy.
AB  - PURPOSE: To assess local retinal function of macula in patients with central
      serous chorioretinopathy (CSC). METHODS: Multifocal electroretinograms (ERGs)
      were recorded in 5 patients with unilateral CSC and 20 normal subjects. The
      waveforms from the central retina within 5 degrees of visual angle were analyzed.
      The first negative trough was designated as N1, the first positive peak as P1,
      and the second trough as N2. RESULTS: The multifocal ERG amplitudes were
      significantly reduced at the first attack of CSC in all patients compared with
      the values in the normal controls, for P1-N1 (P <.01) and for P1-N2 (P <.01).
      Multifocal ERG latencies of the patients significantly increased compared with
      normal controls, for P1 (P <.01) and N2 (P <.01). After the resolution of retinal
      detachment, although the multifocal ERG amplitudes increased markedly, they did
      not improve to the normal level during the follow-up period (4-23 months).
      CONCLUSIONS: Persistent functional impairment of the retina was found by
      multifocal ERGs in patients with CSC after the resolution of subretinal fluid. A
      topographical analysis of the multifocal ERG is useful in the clinical
      observation of CSC.

PMID- 12063044
TI  - The subclassification and long-term prognosis of preproliferative diabetic
      retinopathy.
AB  - PURPOSE: We followed up 54 patients (95 eyes) with preproliferative diabetic
      retinopathy (PPDR) for at least 2 years, and then evaluated the proportion
      developing proliferative diabetic retinopathy (PDR), and the period from
      diagnosis of PPDR until the development of PDR. METHODS: We divided the 95 eyes
      affected by PPDR into 75 eyes with mild-type and 20 eyes with moderate-type based
      on our previously proposed subclassification, and evaluated long-term (2 or more
      years) prognosis. RESULTS: The proportion developing PDR was 24% in mild-type and
      60% in moderate-type. The average period from diagnosis of PPDR until the
      development of PDR was 6 years and 5 months in mild-type, 2 years in moderate
      type. The cumulative occurrence rates of PDR at 2, 5, and 10 years were estimated
      to be 0%, 14%, and 39% in mild-type and 35%, 58%, and 79% in moderate-type,
      respectively. The proportion developing PDR was significantly higher and the
      average period until PDR development significantly shorter in moderate than in
      mild-type. In mild-type eyes, the rate of progression to moderate-type was 56%
      and further progression from moderate-type to PDR occurred in 43%. CONCLUSION:
      The above results again confirm the usefulness of our subclassification, and also
      provide valuable information about the long-term prognosis of PPDR.

PMID- 12063043
TI  - Vitrectomy for diabetic cystoid macular edema.
AB  - PURPOSE: We evaluated visual outcomes following vitrectomy for diabetic cystoid
      macular edema. METHODS: Visual outcomes and factors possibly influencing final
      visual acuity were assessed and documented retrospectively in 45 eyes of 40
      patients, all of whom were followed up for at least 6 months postoperatively.
      RESULTS: Compared with the preoperative logarithm of the minimum angle of
      resolution (logMAR) visual acuity, final logMAR visual acuity improved 0.2 or
      more in 51% of the eyes, was unchanged in 47%, and decreased 0.2 or more in 2%. A
      final postoperative visual acuity of 0.5 or better was achieved in 38%.
      Preoperative visual acuity and the extent of the cystoid space on fluorescein
      angiography were significantly related to final visual acuity. A final
      postoperative visual acuity of 0.5 or better was noted in 8% of eyes with a
      preoperative visual acuity below 0.1, in 50% of eyes with a preoperative visual
      acuity of 0.1 or better, in 71% of eyes with a cystoid space smaller than 5 disc
      areas, and in 20% of eyes with a cystoid space of 5 disc areas or more. The state
      of the posterior vitreous membrane did not influence final visual acuity. There
      were no complications that decreased visual acuity. CONCLUSIONS: We conclude that
      diabetic cystoid macular edema is a good indication for vitrectomy, regardless of
      the state of the posterior vitreous membrane. A preoperative visual acuity of 0.1
      or better and/or a cystoid space smaller than 5 disc areas may be indications for
      surgery aimed at achieving a final postoperative visual acuity of 0.5 or better.

PMID- 12063045
TI  - Indocyanine green angiographic findings in acute retinal necrosis.
AB  - PURPOSE: To clarify indocyanine green (IA) angiographic features in patients with
      acute retinal necrosis (ARN). METHODS: Two patients with ARN were examined by
      fluorescein angiography (FA) and IA, and findings from both were compared.
      RESULTS: Fundus examination revealed widespread retinal hemorrhages and yellowish
      white patches in the periphery, characteristic of ARN. In both cases, FA showed
      diffuse dye leakage from all retinal veins and the optic disc, and vascular
      obstruction in the peripheral fundus. In IA, dye leakage was localized, and
      extravasation of dye was evident only from the lower temporal retinal vein and
      the lower half of the optic disc. This pattern of indocyanine green dye leakage
      appeared to be continuous from the optic disc toward the lower temporal retinal
      vein. Also, IA clearly demonstrated choroidal vascular filling delay in one case
      in the early phase of the angiogram. CONCLUSIONS: While FA showed diffuse dye
      leakage from all retinal veins, IA identified only the retinal vessels with the
      most prominent vascular damage. IA also identified choroidal vascular lesions in
      these patients with ARN. The information obtained by IA might be useful to detect
      retinal vasculitis with prominent inflammation and to determine the extent of
      choroidal inflammation in patients with ARN.

PMID- 12063046
TI  - A novel mutation of the OPA1 gene in a Japanese family with optic atrophy type 1.
AB  - PURPOSE: To report a novel mutation of the OPA1 gene in a Japanese family with
      optic atrophy type 1 (OPA1) and to describe the clinical features of this family.
      METHODS: Standard ocular examinations were performed on the proband and his two
      affected sons. The DNA sequence of all exons and splice sites of the OPA1 gene
      was determined to detect mutations. RESULTS: The proband and his sons had a
      heterozygous mutation of the OPA1 gene in the third nucleotide of intron 12
      (IVS12+3A-->T). Clinically, each patient had reduced visual acuity (onset within
      the first 6 years of life) and optic nerve pallor. The proband showed bilateral
      central scotomas and generalized dyschroatopsia. This is the first report of OPA1
      gene mutation in Japanese patients with familial optic atrophy. CONCLUSIONS: A
      mutation of the OPA1 gene was detected in a Japanese family with OPA1, which
      follows the same pattern as reported in Western countries. It is suggested that
      mutations of the OPA1 gene contribute to the development of optic nerve atrophy
      regardless of ethnic groups. Screening for the OPA1 gene mutation will be useful
      for diagnosis of OPA1 in Japanese patients.

PMID- 12063047
TI  - Colour Doppler imaging of superior ophthalmic vein in thyroid-associated eye
      disease.
AB  - PURPOSE: One of the possible etiologies of proptosis in patients with thyroid
      associated eye disease is stated to be passive orbital venous congestion caused
      by the occlusive and constrictive changes of the superior ophthalmic vein (SOV).
      In an attempt to clarify the validity of this claim, quantitative information on
      the flow velocity of the SOV was obtained by colour Doppler imaging in 24
      patients with thyroid-associated eye disease and compared with data from the
      control group. METHODS: On clinical examination, ocular motility, proptosis, soft
      tissue involvement, and the presence of optic neuropathy were evaluated. The
      interaction of these signs with the flow velocity of the SOV was investigated in
      conjunction with computed tomographic (CT) findings such as extraocular muscle
      enlargement, dilatation of the SOV, and apical crowding of the orbit. RESULTS:
      The mean blood flow velocity was significantly decreased in patients compared to
      the control group (P <.05). The CT measures that contributed to significant
      decreases in SOV blood flow velocity were apical crowding (P <.05) and the
      coexistence of horizontal and vertical extraocular muscle involvement (P <.05).
      Among the clinical measures, significant decreases could be attributed to soft
      tissue findings (P <.01) and to optic neuropathy (P <.05). CONCLUSIONS: External
      compression of the SOV may contribute to the SOV blood flow decrease in orbits
      afflicted with thyroid eye disease, but proptosis is not relevant to the SOV
      blood flow decrease.

PMID- 12063048
TI  - Fornix and conjunctiva reconstruction by amniotic membrane in a patient with
      conjunctival mucosa-associated lymphoid tissue lymphoma.
AB  - BACKGROUND: Conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma is a
      rare, low-grade, non-Hodgkin's B-cell lymphoma. Herein, we report our successful
      management of the large conjunctival defect caused by resection of conjunctival
      MALT lymphoma by covering it with transplanted amniotic membrane. CASE: A 28-year
      old Japanese man, who had been diagnosed histologically as having conjunctival
      MALT lymphoma in his left eye, was referred to us for treatment. The tumor was
      located on the lower bulbar and palpebral conjunctiva, and involved the fornix.
      Extensive resection of the conjunctival lesion was performed. Two pieces of
      amniotic membrane were used to reconstruct the fornix, bulbar, and palpebral
      conjunctival defect. OBSERVATIONS: Epithelialization over the transplantation was
      completed within 3 weeks when all sutures were removed. During the 6 months of
      follow-up, there was no recurrence or any postoperative complication, such as
      graft rejection, symblepharon, or chronic inflammation. CONCLUSIONS: We
      demonstrated for the first time that amniotic membrane can be used to cover a
      large defect on both bulbar and palpebral conjunctiva when such a low-grade
      malignancy as MALT lymphoma is extensively excised. Amniotic membrane
      transplantation was quite effective for the fornix and conjunctival
      reconstruction.

PMID- 12063062
TI  - In vivo antimutagenic effect of vitamins C and E against rifampicin-induced
      chromosome aberrations in mouse bone-marrow cells.
AB  - -The genotoxic effect of rifampicin (RMP), one of the most active
      antituberculosis agents is studied. Also, the possible protection provided by the
      natural antioxidant vitamins C (VC) and E (VE) against the genotoxic effect of
      RMP is assessed. Mice were orally treated by gavage with 10, 50, 150 and 300 mg
      RMP kg(-1) body weight (bw). Also, oral treatment was conducted with RMP plus the
      vitamins. Mice received 300 mg RMP kg(-1) bw plus 100, 200 and 400mg VC or VE kg(
      1) bw. Samples were taken 24h after the treatment. Repeated treatments with: (1)
      the therapeutic dose of RMP (10 mg kg(-1) bw); (2) RMP plus a dose of 25, 50 and
      75 mg VC kg(-1); (3) RMP plus 10, 20 and 40 mg VE kg(-1) bw for 30 consecutive
      days were conducted. The tested doses of RMP induced a significant increase in
      the percentage of chromosome aberrations. However, a lower percentage of
      chromosome aberrations was observed when animals were treated with the
      therapeutic dose for 30 consecutive days. The obtained results revealed that
      chromosome aberrations induced by RMP decreased to a significant extent when mice
      were treated with RMP plus VC. The repeated doses of VC reduced the percentage of
      chromosome aberrations induced by RMP in a significant and dose-dependent manner.
      On the other hand, repeated doses of VE were not very effective in reducing the
      percentage of chromosome aberrations induced by RMP. Only the highest dose (3 x
      40 mg kg(-1) bw) showed a significant effect (P<0.01). The results on the
      induction of chromosome damage clearly show that only VC appears able to
      efficiently protect the bone-marrow cells when given together with RMP, while no
      significant reduction in the yield of chromosome aberrations was observed for VE
      in combination with the antituberculosis drug.

PMID- 12063063
TI  - A modified neutral comet assay: elimination of lysis at high temperature and
      validation of the assay with anti-single-stranded DNA antibody.
AB  - Comet assay under neutral conditions allows the detection of DNA double-strand
      breaks (DSB), considered to be the biologically relevant radiation-induced
      lesion. In this report, we describe modifications of the neutral comet method,
      which simplify and facilitate its use for estimation of DNA DSB in X-irradiated
      mammalian cells in culture. The analysis carried out according to this protocol
      takes less time than those most often applied. Also, the use of lysis at 50
      degrees C is avoided; this is important in view of the presence of heat-labile
      sites in the chromatin of irradiated cells, recently reported by Rydberg
      [Radiation-induced heat-labile sites that convert into DNA double-strand breaks,
      Radiation Research 153 (2000) 805-812]. The comets have well-defined, sharp
      limits, suitable for image analysis. The chromatin of the hydrogen peroxide
      treated or UV-C-irradiated cell remains condensed similarly to that of the
      control cells. We checked the neutral comets for the presence of single-stranded
      DNA by means of a specific antibody. The results point to a satisfactory
      sensitivity of the modified neutral comet assay and its specificity for DSB. The
      minimum detection level of the modified neutral comet assay is about 5 Gy.

PMID- 12063064
TI  - Genotoxicity of the Kishon River, Israel: the application of an in vitro cellular
      assay.
AB  - The alkaline comet assay, a sensitive method for DNA strand breaks and alkali
      labile site detection in individual cells, was employed here as an
      ecotoxicological monitoring tool for evaluation of genotoxicity in the Kishon
      River, Israel. This river, the most polluted river in Israel, has recently
      elicited major public concern with regard to cancer incidences in people who have
      dived there over many years. Five water samples were collected every odd month
      throughout the year 2001, from four localities. The comet assay was employed on
      fish hepatoma cell line RTH-149. Cells were exposed for 2h, in triplicate, to
      Kishon water: medium (1:1) samples that were pre-adjusted for pH and salinity
      percentage levels. Three DNA damage parameters (comet percentages, score of
      damage, and cumulative tail lengths of the comet), revealed significantly higher
      genotoxic values in Kishon water-treated cells as compared with the controls (up
      to 2.4, 3.2, and 3.6-fold, respectively). Part of the sampling sites revealed
      higher genotoxicity than other polluted sites. The results of this study
      demonstrate that the comet assay with RTH-149 cells can be successfully applied
      to a variety of aquatic samples revealing freshwater, marine and estuary
      conditions. The method found to be fast, sensitive, and suitable for monitoring
      programs.

PMID- 12063065
TI  - Collaborative validation study of the in vivo micronucleus test using mouse
      colonic epithelial cells.
AB  - The in vivo micronucleus test using mouse colonic epithelial cells was evaluated
      as the 11th collaborative study organized by the Collaborative Study Group on the
      micronucleus test (CSGMT) with three model chemicals that were known to induce
      chromosome damage in mouse colonic cells. Five laboratories participated in this
      validation study. All three model chemicals, i.e. 1,2-dimethylhydrazine
      dihydrochloride (1,2-DMH), N-methyl-N-nitrosourea (MNU), and mitomycin C (MMC),
      induced micronucleated colonic epithelial cells in a 4-day exposure protocol in
      all participating laboratories. We confirmed that the present single cell
      suspension method could be used to detect the model chemicals as micronucleus
      inducers in mouse colonic epithelial cells. Advantages of this method are that
      experiments are easy to perform and that intact cells can be analyzed. The
      present study suggested that the colon micronucleus assay proposed here is useful
      for mechanistic studies of colon carcinogenesis.

PMID- 12063066
TI  - Mitochondrial DNA mutations in the parotid gland of cigarette smokers and non
      smokers.
AB  - It has previously been demonstrated that mitochondrial DNA (mtDNA) mutations
      accumulate in the lung and increase in frequency with age. It has also been shown
      that the level of mtDNA mutations including deletions and base substitutions are
      elevated in lung tissue of smokers relative to non-smokers. We have previously
      shown that the 'common' 4977 bp mtDNA deletion is present in the parotid
      (salivary) gland of smokers and non-smokers and that there is a significant
      increase in the level of this deletion in Warthins tumour, an oncocytoma of the
      parotid gland. In this study we used semi-quantitative PCR to confirm the
      presence of 4977 bp mtDNA deletion in the parotid gland of non-smokers and
      smokers. Importantly, we show that the deletion accumulates with age regardless
      of smoking status and that there was no significant difference in the level of
      the 4977 bp deletion in parotid tissue of smokers and non-smokers. Using strand
      conformational polymorphism (SSCP) and direct sequencing we also found 5/23
      smokers had parotid tissue specific base substitutions: either an A/T to G/C
      transition at A4767 or a G/C to A/T transition at G4853. These results are
      evidence of age related increase in the 4977 bp deletion and a higher level of
      mutations, probably due to oxidative damage, in the parotid gland of smokers.

PMID- 12063067
TI  - Detection of mutation in transgenic CHO cells using green fluorescent protein as
      a reporter.
AB  - A novel approach was developed for rapidly estimating the frequency of specific
      mutations in genetically engineered Chinese hamster ovary (CHO) cells. We
      designed double-transgenic CHO cell lines that contain a transgene consisting of
      the sequence coding for green fluorescent protein under the control of a
      tetracycline (Tet) responsive promoter and a second transgene coding for the
      constitutively expressed Tet repressor. Cultures of these CHO cells were treated
      with gamma-radiation, N-methyl-N-nitrosourea or methyl methanesulfonate, and the
      fluorescence of individual cells from both control and treated cultures was
      measured by flow cytometry. The treatments increased the number of highly
      fluorescent cells, those with presumed mutations in the Tet-repressor gene.
      Mutant cells from gamma-radiation-exposed cultures were isolated by fluorescence
      activated cell sorting, cultured, and individual clones expanded. A PCR-based
      analysis indicated that the highly fluorescent expanded cells had lost the
      transgene coding for the Tet repressor, suggesting that the system mainly detects
      large genetic alterations. A similar approach may be useful for making high
      throughput in vivo models for mutation detection.

PMID- 12063068
TI  - The effects of oral glutamine on cisplatin-induced genotoxicity in Wistar rat
      bone marrow cells.
AB  - Several studies have suggested that dietary supplementation with antioxidants can
      influence the response to chemotherapy as well as the development of adverse side
      effects that result from treatment with antineoplastic agents. The emphasis of
      the present study was to investigate whether the administration of a single dose
      of oral glutamine had any protective effect against cisplatin-induced
      clastogenicity. Cisplatin was administered to Wistar rats either alone or after
      treatment with glutamine. The rats were treated with glutamine (300 mg/kg b.w.)
      by gavage 24h before the administration of cisplatin (5mg/kg b.w., i.p.) and then
      sacrificed 24h after treatment with cisplatin. Glutamine significantly reduced
      (by about 48%) the clastogenicity of cisplatin in rat bone marrow cells. The
      antioxidant action of glutamine presumably modulates the clastogenic action of
      cisplatin.

PMID- 12063069
TI  - Curcumin disrupts mitotic spindle structure and induces micronucleation in MCF-7
      breast cancer cells.
AB  - The dietary phytochemical curcumin possesses anti-inflammatory, -oxidant, and
      cytostatic properties, and exhibits significant potential as a chemopreventative
      agent in humans. Although many cell types are arrested in the G2/M-phase of the
      cell cycle after curcumin treatment, the mechanisms by which this occurs are not
      well understood. The purpose of this study was to examine the effects of curcumin
      on the cell cycle of MCF-7 breast cancer cells to determine whether growth arrest
      is associated with structural changes in cellular organization during mitosis.
      For this purpose, MCF-7 breast cancer cells were treated with 10-20 microM
      curcumin, and the effects on cell proliferation and mitosis studied. Structural
      changes were monitored by immunolabeling cells with antibodies to a number of
      cytoplasmic and nuclear proteins, including beta-tubulin, NuMA, lamins A/C and
      B1, lamin B receptor, and centromere antigens. At the concentrations used, a
      single dose of curcumin does not induce significant apoptosis, but is highly
      effective in inhibiting cell proliferation for over 6 days. During the first 24
      48 h of treatment, many cells are arrested in M-phase, and DNA synthesis is
      almost completely inhibited. Remarkably, arrested mitotic cells exhibit monopolar
      spindles, and chromosomes do not undergo normal anaphase movements. After 48 h,
      most cells eventually leave M-phase, and many form multiple micronuclei instead
      of individual daughter nuclei. These observations indicate that the curcumin
      induced G2/M arrest previously described for MCF-7 cells is due to the assembly
      of aberrant, monopolar mitotic spindles that are impaired in their ability to
      segregate chromosomes. The production of cells with extensive micronucleation
      after curcumin treatment suggests that at least some of the cytostatic effects of
      this phytochemical are due to its ability to disrupt normal mitosis, and raises
      the possibility that curcumin may promote genetic instability under some
      circumstances.

PMID- 12063070
TI  - Effects of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) and vitamin E on 4
      nitroquinoline-N-oxide (4-NQO)-induced mutagenesis in lacZ mouse upper
      aerodigestive tissue.
AB  - The effects of dietary administration of 1,4-phenylenebis(methylene)selenocyanate
      (p-XSC) and Vitamin E on 4-nitroquinoline-N-oxide (4-NQO)-induced mutagenesis in
      lacZ mouse upper aerodigestive tissues were investigated. 4-NQO was a potent
      mutagen in tongue, other pooled oral tissues and esophagus when given in drinking
      water for 4 weeks at a concentration of 20 microg/ml [corrected]. The mutant
      fractions (MFs) in these tissues were: 144+/-73, 130+/-52 and 61+/-24
      mutants/10(5), respectively. Background levels were 3.7+/-1.9 in tongue, 2.9+/
      1.2 in esophagus and 2.4+/-1.0 in pooled oral tissue. Vitamin E at levels of 200
      and 400 IU/kg diet led to no significant effects on mutagenesis although a small
      decrease in the MF was observed in all tissues at the higher dose. Dietary p-XSC
      at levels of 2.5 and 10 ppm selenium also resulted in no statistically
      significant effects on mutagenesis, but mutagenesis was somewhat reduced in
      esophagus and pooled oral tissue at the higher dose. However, the combination of
      the low doses of p-XSC and Vitamin E resulted in nearly a 40% decrease in
      mutagenesis in tongue and esophagus, and this decrease was statistically
      significant (P=0.008 and 0.023, respectively. No inhibition was observed using a
      combination of the higher doses of p-XSC and Vitamin E. These results lend
      support to the use of low doses of inhibitors of mutagenesis in combinations. The
      application of in vivo mutagenesis assays to the screening of chemopreventive
      agents enables investigators to evaluate potential inhibitors when given
      individually and in combinations on the initiation stage of carcinogenesis in a
      short-term in vivo bioassay.

PMID- 12063071
TI  - Evaluation of genotoxicity of captan, maneb and zineb in the wing spot test of
      Drosophila melanogaster: role of nitrosation.
AB  - The wing spot test in Drosophila melanogaster is a suitable system for the
      analysis of genotoxic activity of compounds that need metabolic transformation to
      render them active. We have analysed the genotoxicity of three fungicides for
      which it was reported that the metabolic processes taking place in vivo may
      determine their activity. The compounds analysed are captan, maneb, zineb and
      ethylenethiourea (ETU) (a metabolic derivative of ethylenebisdithiocarbamates
      like maneb and zineb). We have also evaluated the ability of ETU to form
      genotoxic derivatives in vivo analysing this compound in combined treatments with
      sodium nitrite. Both standard and high bioactivation NORR strains have been used.
      Captan, usually considered a mutagen in vitro but a non-mutagen in vivo, gave
      negative results in the wing spot test with both crosses. Positive results were
      obtained for maneb in the standard cross and for ETU in both the standard and the
      high bioactivation cross. The genotoxicities of maneb and ETU were higher when
      treatments were made on media in which nitrosation is favoured. A low absorption
      of the fungicide and an inefficient availability of the compound in the target
      may explain negative results obtained with zineb in both crosses. The results
      obtained in this study with the wing spot test demonstrate once again the
      suitability of this in vivo assay, in which absorption, distribution and
      metabolism processes take place, for the evaluation of genotoxicity of compounds
      to which humans are exposed.

PMID- 12063072
TI  - Risperidone prolongs cardiac action potential through reduction of K+ currents in
      rabbit myocytes.
AB  - Prolongation of QT interval by antipsychotic drugs is an unwanted side effect
      that may lead to ventricular arrhythmias. The antipsychotic agent risperidone has
      been shown to cause QT prolongation, especially in case of overdosage. We
      investigated risperidone effects on action potentials recorded from rabbit
      Purkinje fibers and ventricular myocardium and on potassium currents recorded
      from atrial and ventricular rabbit isolated myocytes. The results showed that (1)
      risperidone (0.1-3 microM) exerted potent lengthening effects on action potential
      duration in both tissues with higher potency in Purkinje fibers and caused the
      development of early afterdepolarizations at low stimulation rate; (2)
      risperidone (0.03-0.3 microM) reduced significantly the current density of the
      delayed rectifier current and at 30 microM decreased the transient outward and
      the inward rectifier currents. This study might explain QT prolongation observed
      in some patients treated with risperidone and gives enlightenment on the risk of
      cardiac adverse events.

PMID- 12063073
TI  - KF26777 (2-(4-bromophenyl)-7,8-dihydro-4-propyl-1H-imidazo[2,1-i]purin-5(4H)-one
      dihydrochloride), a new potent and selective adenosine A3 receptor antagonist.
AB  - We investigated the biochemical and pharmacological properties of a new adenosine
      A(3) receptor antagonist, KF26777 (2-(4-bromophenyl)-7,8-dihydro-4-propyl-1H
      imidazo[2,1-i]purin-5(4H)-one dihydrochloride). This compound was characterized
      using N(6)-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide ([125I]AB-MECA)
      or [35S]guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding to membranes from
      human embryonic kidney 293 (HEK293) cells expressing human adenosine A(3)
      receptors. KF26777 showed a K(i) value of 0.20+/-0.038 nM for human adenosine
      A(3) receptors labeled with [125I]AB-MECA and possessed 9000-, 2350- and 3100
      fold selectivity vs. human adenosine A(1), A(2A) and A(2B) receptors,
      respectively. The inhibitory mode of binding was competitive. KF26777 inhibited
      the binding of [35S]GTPgammaS stimulated by 1 microM 2-chloro-N(6)-(3
      iodobenzyl)adenosine-5'-N-methyluronamide (Cl-IB-MECA). The IC(50) value was
      270+/-85 nM; the compound had no effect on basal activity. Dexamethasone
      treatment for HL-60 cells, human promyelocytic leukemia, up-regulated functional
      adenosine A(3) receptors expression, and resulted in the enhanced elevation of
      intracellular Ca(2+) concentration ([Ca(2+)](i)) via the adenosine A(3) receptor.
      KF26777 antagonized this [Ca(2+)](i) mobilization induced by Cl-IB-MECA, with a
      K(B) value of 0.42+/-0.14 nM. These results indicate that KF26777 is a highly
      potent and selective antagonist of the human adenosine A(3) receptor.

PMID- 12063074
TI  - Differential taurine responsiveness to ethanol in high- and low-alcohol sensitive
      rats: a brain microdialysis study.
AB  - Several microdialysis studies have investigated the effects of acute ethanol on
      extracellular amino acids in various rat brain regions. However, these studies
      led to conflicting results, suggesting that individual differences between rat
      strains and lines may play an important role. In the present study, high-alcohol
      sensitive (HAS) and low-alcohol sensitive (LAS) rats were used to investigate the
      possible relationship between ethanol sensitivity and the concentrations of
      extracellular amino acids in the nucleus accumbens. Several groups of HAS and LAS
      rats were injected with either saline or ethanol (1.0, 2.0 or 3.0 g/kg, i.p.) and
      the concentrations of amino acids in the nucleus accumbens microdialysates were
      assayed by electrochemical detection. Acute ethanol induced a dose-dependent
      increase in extracellular taurine concentrations. However, this increase was
      significantly reduced at 2.0 and 3.0 g/kg ethanol in HAS rats relative to LAS
      rats. Since the biological functions of taurine suggest its implication in the
      reduction of ethanol adverse effects, a higher increase in taurine concentrations
      may contribute to the lower ethanol sensitivity of LAS rats. Although 2.0 and 3.0
      g/kg ethanol did not affect extracellular glutamate concentrations, a significant
      increase in glutamate was observed after 1.0 g/kg ethanol to HAS rats but not to
      LAS rats. Such an effect remains unexplained but suggests that discrepancies
      between the results of previous microdialysate studies may be related to
      differences in the ethanol sensitivities of various rat strains.

PMID- 12063075
TI  - Repeated imipramine and electroconvulsive shock increase alpha 1A-adrenoceptor
      mRNA level in rat prefrontal cortex.
AB  - alpha(1)-Adrenoceptors have been implicated in the mechanism of action of
      antidepressants, but their action on specific receptor subtypes was rarely
      reported. We compared now the action of two prototypic antidepressant treatments:
      repeated imipramine and electroconvulsive shock, on the expression of the
      alpha(1A)- and alpha(1B)-adrenoceptor mRNAs and on the receptor density in rats.
      The mRNA expression was assessed by Northern blot in the prefrontal cortex and
      the hippocampus, the receptor density was measured by [3H]prazosin binding in the
      total cerebral cortex and hippocampus. In the cortex, both treatments elevated
      the alpha(1A)-adrenoceptor mRNA and the expression of receptor protein. The
      expression of alpha(1B)-adrenoceptor mRNA remained unaffected. In contrast, in
      the hippocampus, the antidepressant treatments augmented the density of alpha(1A)
      adrenoceptor protein without changing the level of its mRNA expression there. The
      results suggest that the alpha(1A)-adrenoceptor subtype is specifically involved
      in the mechanism of action of classical antidepressant treatments.

PMID- 12063076
TI  - Dopamine D1 receptors and adenosine A1 receptors in the rat nucleus accumbens
      regulate motor activity but not prepulse inhibition.
AB  - Locomotor activity and sensorimotor gating (measured as prepulse inhibition of
      startle) are regulated by mesoaccumbal dopamine. Recent evidence indicated
      antagonistic interactions between adenosine A(1) receptors and dopamine D(1)
      receptors, as well as between adenosine A(2) receptors and dopamine D(2)
      receptors in the nucleus accumbens. Therefore, it is conceivable that accumbal
      dopamine and adenosine are both involved in the regulation of prepulse inhibition
      and locomotion. We tested whether accumbal adenosine A(1) and dopamine D(1)
      receptors control locomotor activity and prepulse inhibition using the following
      four treatments. (1) Injections of the selective adenosine A(1) receptor agonist
      N(6)-cyclopentanyladenosine (CPA 1.5 and 3 microg/microl per side) into the
      nucleus accumbens. (2) Stimulation of the ventral tegmental area by local
      infusion of the GABA(A) receptor antagonist picrotoxin (25-100 ng/0.5 microl
      bilaterally). (3) Picrotoxin injections into the ventral tegmental area (100
      ng/0.5 microl) and simultaneous bilateral injections of CPA (3 microg/microl per
      side) into the nucleus accumbens. (4) Injections of the selective dopamine D(1)
      receptor antagonist SCH 23390 (3 microg/0.5 microl per side) into the nucleus
      accumbens and ventral tegmental area stimulation by picrotoxin. Intra-accumbal
      CPA infusion reduced locomotor activity but had no effect on prepulse inhibition.
      Picrotoxin stimulation of the ventral tegmental area increased locomotor activity
      which was antagonized by co-administration of CPA or SCH 23390 into the nucleus
      accumbens. An enhancement of prepulse inhibition was observed after stimulation
      of the ventral tegmental area and co-administration of SCH 23390 into the nucleus
      accumbens. These findings demonstrate that adenosine A(1) and dopamine D(1)
      receptors are involved in the regulation of locomotor activity mediated by the
      mesoaccumbal dopamine system. The finding that locomotor effects induced by
      stimulation of the mesoaccumbal dopamine system were not accompanied by a
      prepulse inhibition-deficit suggests a dissociation of the neuronal substrates
      involved in the control of locomotion and the regulation of sensorimotor gating.

PMID- 12063077
TI  - Cannabinoids inhibit pre- and postjunctionally sympathetic neurotransmission in
      rat mesenteric arteries.
AB  - The effects of cannabinoids on sympathetic neurotransmission in the rat isolated
      perfused mesenteric arterial bed, were investigated. Electrically evoked
      sympathetic neurogenic vasocontraction was inhibited by the cannabinoid receptor
      agonists 11-hydroxy-dimethylheptyl-Delta(8)-tetrahydrocannabinol (HU210), (-)-cis
      3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]trans-4-(3-hydroxypropyl)-cyclohexanol
      (CP55,940) and methanandamide, and by (+)-11-hydroxy-Delta(8)
      tetrahydrocannabinol (HU211), a (+)-stereoisomer of HU210. The inhibition was
      unaffected by cannabinoid CB(1) and CB(2) receptor antagonists. Electrically
      evoked release of endogenous noradrenaline from sympathetic nerves was inhibited
      by HU210, but not by HU211. Inhibition was blocked by a cannabinoid CB(1), but
      not a CB(2), receptor antagonist. HU210 attenuated contractions to noradrenaline,
      and all of the cannabinoids blocked contractions to KCl. Capsaicin pre-treatment
      had no significant effect on HU210- and CP55,940-mediated inhibition of
      sympathetic neurogenic contraction, but partly blocked inhibition mediated by
      methanandamide. These data show that cannabinoids can inhibit, by distinct pre-
      and postjunctional actions, sympathetic neurotransmission in the rat mesenteric
      arterial bed. The pre-junctional action is mediated by a cannabinoid CB(1)-like
      receptor, but the postjunctional action does not appear to involve either
      cannabinoid CB(1) or CB(2) receptors.

PMID- 12063078
TI  - Geissoschizine methyl ether, an indole alkaloid extracted from Uncariae Ramulus
      et Uncus, is a potent vasorelaxant of isolated rat aorta.
AB  - Effects of geissoschizine methyl ether, an indole alkaloid isolated from the hook
      of Uncariae Ramulus et Uncus, on vascular responses were examined using isolated
      strips of rat aorta. Geissoschizine methyl ether (10(-7)-10(-4) M) relaxed
      norepinephrine (5x10(-8) M)-induced contraction in a dose-dependent manner. The
      potency (50% efficacy concentration, EC(50)=0.744 microM) was approximately 14
      times greater than that (EC(50)=10.6 microM) of hirsutine, one of the indole
      alkaloids isolated from Uncariae Ramulus et Uncus that demonstrates a
      vasorelaxant effect by Ca(2+)-channel blocking. The vasorelaxant effect of
      geissoschizine methyl ether found at the lower concentrations (10(-7)-3x10(-6) M)
      on the norepinephrine-induced contraction was abolished by pretreatment with N(G)
      nitro-L-arginine (10(-4) M), an inhibitor of nitric oxide synthesis, or by
      denuding aortas of endothelium, while the effects at the higher concentrations
      (10(-5)-10(-4) M) were not completely prevented by either N(G)-nitro-L-arginine
      and deendothelialization. Furthermore, geissoschizine methyl ether did not relax
      high K(+)-, Ca(2+)- and a Ca(2+)-channel agonist Bay K8644-induced contractions
      at the lower concentrations that markedly relaxed the norepinephrine-induced
      contractions, while the higher concentrations of geissoschizine methyl ether
      relaxed the high K(+)-, Ca(2+)- and Bay K8644-induced contractions. These results
      suggest that the vasorelaxant effect of geissoschizine methyl ether is composed
      of two different mechanisms: endothelial dependency with nitric oxide and
      endothelial independency with voltage-dependent Ca(2+)-channel blocking.

PMID- 12063079
TI  - Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal
      and postischemic performance of the isolated rat heart.
AB  - The present study investigated the effects of dronedarone and amiodarone on
      plasma thyroid hormones and the possible consequences on the response of the
      heart to ischemia. Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day
      per os) were administered for 2 weeks in normal and thyroxine-treated animals (25
      microg/100 g body weight od sc, for 2 weeks), while animals without amiodarone
      and dronedarone served as controls. Isolated rat hearts were perfused in a
      Langendorff mode and subjected to 20 and 30 min of zero-flow global ischemia
      followed by 45 min of reperfusion. Functional changes were assessed by measuring
      left ventricular developed pressure (LVDP) under resting conditions and in
      response to ischemia-reperfusion, LVDP%, as well as the severity of ischemic
      contracture. Amiodarone resulted in increased T4, T4/T3 and rT3, whereas
      dronedarone did not alter the thyroid hormone profile in normal animals. In
      thyroxine-treated animals, amiodarone increased T4/T3 ratio but T4, T3 and rT3
      levels were not altered. Basal functional parameters and ischemic contracture did
      not change by amiodarone and/or dronedarone neither in normal nor in thyroxine
      treated hearts. In normal hearts, postischemic functional recovery, LVDP%, was
      not altered by amiodarone or dronedarone administration. LVDP% was statistically
      higher in thyroxine-treated hearts than in normal and this beneficial effect was
      not abolished by amiodarone or dronedarone treatment.

PMID- 12063080
TI  - In vivo effects of fenoldopam on autonomic nervous system after inhibition or
      activation of ganglionic transmission.
AB  - The study investigated the effects of dopamine D1-like receptor stimulation on
      the autonomic nervous system. Fenoldopam (20 microg/kg) was injected i.v. in
      conscious sinoaortic denervated dogs, that is, surgically deprived of baroreflex
      pathways. In barodenervated dogs, fenoldopam (20 microg/kg) induced arterial
      hypotension as well as bradycardia and reduced noradrenaline plasma levels.
      Pentolinium (0.1 mg/kg i.v.), used to induce partial blockade of nicotinic
      ganglionic receptors, suppressed the fenoldopam-induced decrease in sympathetic
      tone, suggesting a ganglionic location for the dopamine D1-like receptor.
      Moreover, the inability of fenoldopam to reduce the nicotine-induced increase in
      sympathetic tone suggests that a postsynaptic ganglionic location can be excluded
      for the dopamine D1-like receptor. The results of these "in vivo" experiments
      strongly suggest a presynaptic location for the ganglionic dopamine D1-like
      receptor, stimulation of which results in a reduction of sympathetic tone.

PMID- 12063081
TI  - Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of
      longitudinal smooth muscle from the guinea-pig distal colon in vitro.
AB  - The effect of 2-arachidonoylglycerol, a cannabimimetic eicosanoid, was studied on
      mucosa-free longitudinal muscle strips isolated from the guinea-pig distal colon.
      In the presence of indomethacin (3 microM) and N(G)-nitro-L-arginine (100
      microM), 2-arachidonoylglycerol (10 nM-10 microM) produced concentration
      dependent and tetrodotoxin (1 microM)-sensitive contractions of the longitudinal
      muscle strips. The contractions were markedly attenuated in the presence of
      atropine (0.2 microM), and partially by hexamethonium (100 microM) pretreatment.
      The response to 2-arachidonoylglycerol was mimicked with N
      arachidonoylethanolamine (anandamide, 0.1-30 microM), another cannabimimetic
      eicosanoid, but the cannabinoid CB(1)/CB(2) receptor agonist, R-[2,3-dihydro-5
      methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3,-de]-1,4-benzoxazin-6-yl]-1
      naphthalenylmethanone (WIN55,212-2) (0.1-10 microM), and the vanilloid receptor
      agonist, (all Z)-(4-hydroxyphenyl)-5,8,11,14-eicosatetraenamide (AM 404) (10-30
      microM), were without effect. The cannabinoid CB(1) receptor antagonist, N
      piperidino-5-(4-chlorophenyl)-l-(2,4-dichlorophenyl)-4-methyl-3-pyrazole
      caroxamide (SR141716A) (1 microM), the cannabinoid CB(2) receptor antagonist, [N
      [1S]-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3
      methylphenyl)-l-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) (1 microM),
      and the vanilloid receptor antagonist, capsazepine (10 microM), did not shift the
      concentration-response curve for 2-arachidonoylglycerol to the right. The
      contractile action of 2-arachidonoylglycerol was also partially attenuated in the
      presence of nordihydroguaiaretic acid (10 microM), a lipoxygenase inhibitor.
      These results indicate that 2-arachidonoylglycerol produces contraction of
      longitudinal muscle of the guinea-pig distal colon via mainly stimulation of
      myenteric cholinergic neurones, and that neither cannabinoid CB(1)/CB(2)
      receptors nor vanilloid receptors contributed to the response. The present
      results suggest the possibility that lipoxygenase metabolites may also
      contribute, at least in part, to the contractile action of 2
      arachidonoylglycerol.

PMID- 12063082
TI  - Influence of aging on gastric ulcer healing activities of cimetidine and
      omeprazole.
AB  - In this study, we compared the effects of cimetidine and omeprazole on the
      healing of acetic acid-induced gastric ulcers in 8-, 48-, and 96-week-old rats.
      The repeated oral administration of cimetidine or omeprazole for 14 consecutive
      days markedly accelerated the ulcer healing in 8- and 48-week-old rats. However,
      both drugs were ineffective in 96-week-old rats. The basal gastric acid secretion
      of 8-, 48-, and 96-week-old rats decreased with aging. A single oral
      administration of cimetidine or omeprazole strongly decreased basal gastric acid
      secretion in the three different ages of rats. Cimetidine and omeprazole produced
      a potent and sustained serum gastrin-elevating action in 8- and 48-week-old rats.
      However, the gastrin-elevating actions of both drugs in 96-week-old rats were
      much weaker than in the 8- and 48-week-old rats. These results indicate that
      cimetidine and omeprazole have potent gastric ulcer healing actions in 8- and 48
      week-old rats, as well as potent serum gastrin-elevating actions, but both drugs
      are ineffective in 96-week-old rats, which have lost their gastrin-elevating
      actions.

PMID- 12063083
TI  - The L-3,4-dihydroxyphenylalanine transporter in human and rat epithelial
      intestinal cells is a type 2 hetero amino acid exchanger.
AB  - Information on the intestinal transport of L-3,4-dihydroxyphenylalanine (L-DOPA)
      is scarce. We present here the functional characteristics and regulation of the
      apical inward L-DOPA transport in two intestinal epithelial cell lines (human
      Caco-2 and rat IEC-6). The inward transfer of L-DOPA and L-leucine was promoted
      through an energy-driven system but with different sensitivity to extracellular
      Na(+) concentration: a minor component of L-leucine uptake (approximately 25%)
      was found to require extracellular Na(+) in comparison with L-DOPA transport
      which was Na(+)-independent. L-DOPA and L-leucine uptake was insensitive to N
      (methylamino)-isobutyric acid, but competitively inhibited by 2
      aminobicyclo(2,2,1)-heptane-2-carboxylic acid (BCH). L- and D-neutral amino
      acids, but not acidic and basic amino acids, markedly inhibited L-DOPA and
      [(14)C]L-leucine accumulation in both cell lines. The [(14)C]L-DOPA and [14C]L
      leucine outward were markedly increased by L-leucine and BCH present in
      extracellular medium, but not by L-arginine. In both cell lines, L-DOPA transport
      was stimulated by acidic pH in comparison with [(14)C]L-leucine inward which was
      pH-independent. In conclusion, it is likely that system B(0) might be responsible
      for the Na(+)-dependent uptake of L-leucine in Caco-2 and IEC-6 cells, whereas
      sodium-independent uptake of L-leucine and L-DOPA may include system type 1 and
      type 2 L-amino acid transporter (LAT1 and LAT2), the activation of which results
      in trans-stimulation of substrates outward transfer.

PMID- 12063084
TI  - The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A
      receptor.
AB  - Aripiprazole, 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy]-3,4-dihydro
      2(1H)-quinolinone, a novel antipsychotic with partial agonist activity at
      dopamine D2 receptors, bound with high affinity to recombinant human 5-HT(1A)
      receptors (h5-HT(1A)) in Chinese hamster ovary cell membranes and displayed
      potent, partial agonism at 5-HT(1A) receptors in a guanosine-5'-O-(3-[(35)S]thio)
      triphosphate ([(35)S]GTP gamma S)-binding assay that was blocked completely by a
      selective 5-HT(1A) receptor antagonist. An interaction with 5-HT(1A) receptors
      may contribute to the overall efficacy of aripiprazole against symptoms of
      schizophrenia, including anxiety, depression, cognitive and negative symptoms,
      and to its favorable side-effect profile. Combined with previous studies
      demonstrating the potent partial agonism of aripiprazole at dopamine D2
      receptors, this study suggests aripiprazole is the first dopamine-serotonin
      system stabilizer.

PMID- 12063085
TI  - RB101(S), a dual inhibitor of enkephalinases does not induce antinociceptive
      tolerance, or cross-tolerance with morphine: a c-Fos study at the spinal level.
AB  - In behavioural tests, RB101 (N-[(S)-2-benzyl-3[(S)(2-amino-4-methyl
      thio)butyldithio]-1-oxopropyl]-L-phenylalanine benzyl ester), a mixed inhibitor
      of enkephalin-degrading enzymes, induces antinociceptive effects without
      producing tolerance, or cross-tolerance with morphine. In the present
      experiments, the acute or chronic effects of enantiomer RB101(S) were examined on
      the response of spinal cord neurons to nociceptive inflammatory stimulation
      (intraplantar injection of carrageenin) using c-Fos studies in awake rats. The
      number of c-Fos immunoreactive nuclei was evaluated in the lumbar spinal cord 90
      min after carrageenin. c-Fos-immunoreactive nuclei were preferentially located in
      the superficial (I-II) and deep (V-VI) laminae of segments L4-L5 (areas
      containing numerous neurones responding exclusively, or not, to nociceptive
      stimuli). In the first experimental series, acute RB101(S) (30 mg/kg, i.v.),
      morphine (3 mg/kg, i.v.), or respective vehicles were injected in rats
      chronically treated with RB101(S) (160 mg/kg/day for 4 days, s.c.). In
      chronically treated RB101(S) rats, both acute RB101(S) and morphine reduced the
      total number of carrageenin-evoked c-Fos-immunoreactive nuclei. In the second
      experimental series, acute RB101(S) (30 mg/kg, i.v.) reduced the total number of
      carrageenin-evoked c-Fos-immunoreactive nuclei with similar magnitude in naive
      and in morphine-tolerant (100 mg/kg/day for 3 days, s.c.) rats. These data
      provide further evidence that different cellular mechanisms occurred after
      chronic stimulation of opioid receptors by morphine or endogenous enkephalins.

PMID- 12063086
TI  - Effect of chronic treatment with the protein kinase C inhibitor staurosporine on
      the acquisition and expression of contextual fear conditioning.
AB  - The present study investigated the effects of acute and chronic administration of
      the protein kinase C inhibitor, staurosporine, on the acquisition and expression
      of conditioned freezing behavior, an index of anxiety induced by conditioned fear
      stress. Results revealed that acute staurosporine (0.01 and 0.1 mg/kg, i.p.) did
      not affect either acquisition or expression of conditioned freezing. Chronic
      staurosporine administration (0.01 or 0.1 mg/kg, i.p., for 14 days) significantly
      reduced the acquisition of conditioned freezing at a dose of 0.1 mg/kg, but
      failed to affect the expression of conditioned freezing at any dose. These
      results suggest the involvement of protein kinase C in synaptic and cellular
      plasticity underlying emotional learning and memory.

PMID- 12063087
TI  - Central effects of 1,4-butanediol are mediated by GABA(B) receptors via its
      conversion into gamma-hydroxybutyric acid.
AB  - The aliphatic alcohol 1,4-butanediol in converted into gamma-hydroxybutyric acid
      (GHB) via two enzymatic steps: first, it is oxidised by alcohol dehydrogenase in
      gamma-hydroxybutyraldehyde; second, the latter is transformed, likely by aldehyde
      dehydrogenase, into GHB. Initially, the present study compared the
      sedative/hypnotic effect of GHB and 1,4-butanediol, measured as loss of righting
      reflex. 1,4-Butanediol was more potent than GHB, presumably because of a more
      rapid penetration of the blood brain barrier. Further alcohol dehydrogenase
      inhibitors, 4-methylpyrazole and ethanol, totally prevented the sedative/hypnotic
      effect of 1,4-butanediol; the aldehyde dehydrogenase inhibitor disulfiram
      partially blocked the sedative/hypnotic effect of 1,4-butanediol. Finally, the
      sedative/hypnotic effect of 1,4-butanediol was antagonised by the GABA(B)
      receptor antagonists, SCH 50911 [(2S)(+)-5,5-dimethyl-2-morpholineacetic acid]
      and CGP 46381 [(3-aminopropyl)(cyclohexylmethyl)phosphinic acid], but not by the
      putative GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5-hydroxy-5H
      benzocyclohept-6-ylideneacetic acid), indicating that it is mediated by GABA(B)
      but not GHB receptors. Taken together, these results suggest that the
      sedative/hypnotic effect of 1,4-butanediol is mediated by its conversion in vivo
      into GHB which, in turn, binds to GABA(B) receptors. Accordingly 1,4-butanediol,
      unlike GHB, failed to displace [(3)H]GHB and [(3)H]baclofen in brain membranes.

PMID- 12063088
TI  - Preconditioning of rat hearts by adenosine A1 or A3 receptor activation.
AB  - Our study in rat hearts examined whether activation of adenosine A(1) or A(3)
      receptors improved functional recovery and reduced apoptosis resulting from low
      flow ischemia. Prior to 30 min low-flow ischemia (0.6 ml/min; 6% of baseline
      flow), Langendorff rat hearts were preconditioned with two 5-min cycles of (a)
      ischemia (PC; n=7), (b) infusion of 250 nM adenosine A(1) receptor agonist 2
      chloro-N(6)-cyclopentyladenosine (CCPA; n=6), or (c) infusion of 50 nM adenosine
      A(3) receptor agonist N(6)-(3-iodobenzyl)-adenosine-5'-N-methyl-uronamide (IB
      MECA; n=8). Recovery of function was improved in PC (71+/-3%), CCPA (68+/-6%) and
      IB-MECA (68+/-4%) groups compared to control hearts (46+/-5%; P<0.05). Cumulative
      release of total purines during ischemia-reperfusion was approx. 50% lower in PC,
      CCPA and IB-MECA groups compared to controls (P<0.05) and was significantly
      correlated to the percentage functional recovery (R(2)=0.55; P<0.05). The number
      of cytosolic histone-associated-DNA fragments, a hallmark of apoptosis and
      measured by Enzyme Linked ImmunoSorbent Assay (ELISA), was small and not
      different between groups after 30 min reperfusion. However, CCPA (0.6+/-0.1
      absorbance units) and MECA (0.7+/-0.1 units; P<0.05 vs. PC) decreased apoptosis
      after 150 min reperfusion compared to PC (1.4+/-0.3 units) and control (1.2+/-0.1
      units) hearts. This study shows that adenosine triggers protection of function in
      preconditioned rat hearts via both the adenosine A(1) and A(3) receptor. In
      clinical practice, pharmacological stimulation of adenosine A(3) receptors may be
      advantageous over adenosine A(1) receptor activation due to a lack of contractile
      side-effects. In contrast to ischemic preconditioning, pharmacological
      stimulation of adenosine A(1) or A(3) receptors reduced apoptosis. Furthermore,
      total purine release may serve as a marker of the degree of functional
      protection.

PMID- 12063089
TI  - Capsaicin-induced nonneural vasoconstriction in canine mesenteric arteries.
AB  - Prolonged cold storage (4 degrees C) of canine mesenteric arteries was used to
      reveal the role of nonneural mechanisms in capsaicin-induced vascular
      contraction. The EC(50) values of capsaicin were 3.0 microM, 670 and 104 nM in
      preparations made fresh, after a 1- or 2-week period of cold storage,
      respectively, indicating an enhanced contractile responsiveness of the denervated
      tissue to capsaicin. A similar exaggerated contractile response was seen with
      phenylephrine exclusively after a 1-week cold storage. For fresh, 1- and 2-week
      cold-stored arteries, the EC(50) of phenylephrine were 248, 38 and 30 nM,
      respectively. The maximum contraction produced by tyramine was decreased with
      time. The results suggest that capsaicin may attain vasoconstriction independent
      of neural elements.

PMID- 12063090
TI  - Metamizol potentiates morphine antinociception but not constipation after chronic
      treatment.
AB  - This work evaluates the antinociceptive and constipating effects of the
      combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely
      and chronically treated (once a day for 12 days) rats. On the 13th day,
      antinociceptive effects were assessed using a model of inflammatory nociception,
      pain-induced functional impairment model, and the charcoal meal test was used to
      evaluate the intestinal transit. Simultaneous administration of morphine with
      metamizol resulted in a markedly antinociceptive potentiation and an increasing
      of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua);
      P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001).
      Antinociceptive effect of morphine was reduced in chronically treated rats (39+/
      10 vs. 18+/-5 au) while the combination-induced antinociception was remained
      similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive
      effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c.
      (P<0.05), suggesting the partial involvement of the opioidergic system in the
      synergism observed. In independent groups, morphine inhibited the intestinal
      transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively,
      suggesting that tolerance did not develop to the constipating effects. The
      combination inhibited intestinal transit similar to that produced by morphine
      regardless of the time of treatment, suggesting that metamizol did not potentiate
      morphine-induced constipation. These findings show a significant interaction
      between morphine and metamizol in chronically treated rats, suggesting that this
      combination could be useful for the treatment of chronic pain.

PMID- 12063091
TI  - Morphine analgesia suppresses tumor growth and metastasis in a mouse model of
      cancer pain produced by orthotopic tumor inoculation.
AB  - The present study was conducted to clarify whether relief from cancer pain by
      morphine would suppress tumor growth and metastasis. When given orthotopic
      inoculation of B16-BL6 melanoma cells into the hind paw, C57BL/6 mice showed
      moderate and marked hyperalgesia on days 7-10 and from day 14 post-inoculation,
      respectively. The volume of inoculated hind paw was increased exponentially as a
      function of time from day 8 post-inoculation, a phenomena being due to melanoma
      growth. Lung metastasis was apparent after day 12 post-inoculation. On day 16
      post-inoculation, the hyperalgesia was completely inhibited by subcutaneous
      injection of morphine hydrochloride (5 and 10 mg/kg). The tumor growth and lung
      metastasis were markedly inhibited by repeated administration of morphine (5 and
      10 mg/kg daily for 6 days) and also by the neurectomy of sciatic nerve
      innervating the inoculated region. The results suggest that relief from cancer
      pain by morphine inhibits tumor growth and metastasis.

PMID- 12063092
TI  - Regulation of kinin receptors in airway epithelial cells by inflammatory
      cytokines and dexamethasone.
AB  - The two kinin receptors, B(1) and B(2), are upregulated in inflammation and may
      play a role in diseases such as asthma. In pulmonary A549 cells, TNF-alpha or
      interleukin-1 beta dramatically increased bradykinin B(1) and B(2) receptor mRNA
      expression and this response was prevented by dexamethasone. In primary human
      bronchial epithelial cells, bradykinin B(1) receptor mRNA expression showed a
      similar trend, whereas bradykinin B(2) receptor showed almost constitutive
      expression. Radioligand-binding studies revealed significant increases in
      bradykinin B(2) receptor protein expression following both interleukin-1 beta and
      TNF-alpha treatment of A549 cells; however, no evidence was found for bradykinin
      B(1) receptor. Functionally, the bradykinin B(2) receptor ligand, bradykinin, but
      not the B(1) ligand, des-Arg(10)-kallidin, produced a marked increase in
      prostaglandin E(2) release when administered following interleukin-1 beta
      treatment. Arachidonic acid release in response to bradykinin was markedly
      enhanced by prior incubation with interleukin-1 beta and this was prevented by
      the prior addition of dexamethasone.

PMID- 12063093
TI  - Anti-inflammatory effects of cerebrocrast in a model of rat paw edema and on
      mononuclear THP-1 cells.
AB  - Cerebrocrast (IOS 1.1212; 4-[2-(difluoromethoxy)phenyl]-2,6-dimethyl-1,4
      dihydropyridine-3,5-dicarboxylic acid di(2-propoxyethyl) diester) is a novel
      derivative of 1,4-dihydropyridine, which does not antagonize Ca(2+) influx in
      neuronal tissues. Since several classical dihydropyridines possess anti
      inflammatory properties, we first studied the effects of cerebrocrast in a model
      of rat paw edema induced by carrageenan. Cerebrocrast had a preventative effect
      in this model of inflammation, with maximal activity (32-45% inhibition) in the
      0.1-0.25 mg kg(-1) range. It was ineffective when added after the injection of
      carrageenan. Subsequent in vitro experiments showed that cerebrocrast in the
      micromolar range inhibited secretion of interleukin-1 beta, interleukin-6 and
      neurotoxic products by cells of the human monocytic THP-1 line while failing to
      affect secretion of tumor necrosis factor (TNF-alpha). It also lacked any direct
      neuroprotective effect against toxic secretions from stimulated THP-1 cells. The
      data obtained suggest that cerebrocrast may be useful not only in various
      inflammatory disorders of peripheral tissues, but also in treating
      neurodegenerative diseases, where inflammatory mechanisms in general and
      microglial activation, in particular, are thought to play an important role.

PMID- 12063094
TI  - Beneficial effect of a novel non-steroidal anti-inflammatory agent with basic
      character and antioxidant properties on experimental colitis in rats.
AB  - Ulcerative colitis is a chronic disorder of unknown etiology. Conservative
      treatment remains empirical, even today. The aim of this study was to test the
      efficacy of a novel non-steroidal anti-inflammatory agent [5-(2-hydroxy
      ethylamino)-1-cyclohexyl-2-pentanone] (compound A), with basic character and
      antioxidant properties on an experimental model of ulcerative colitis in rats.
      The effect of this compound was compared with that of methylprednisolone on the
      histological abnormalities and serum levels of tumor necrosis factor-alpha (TNF
      alpha) in experimental colitis produced by 2,4,6-trinitrobenzenesulfonic acid
      (TNB). A total number of 24 rats were randomly assigned to one of four groups of
      six rats each. Group 1: colitis without treatment (disease control), group 2:
      normal animals (control), group 3: induction of experimental colitis treated with
      methylprednisolone (5.3 x 10(-3) mmol/kg i.v. every day for 7 days) and group 4:
      induction of experimental colitis plus administration of compound A (0.6 mmol/kg
      i.v. every day for 7 days). The administration of compound A resulted in a
      statistically significant reduction of the extent of tissue damage and of certain
      histological features (edema, inflammatory infiltration) (P<0.05). Compound A
      also resulted in a statistically significant reduction of the levels of serum TNF
      alpha, compared to those of controls (P<0.005). The beneficial effect of this
      compound was probably due to the combination, on a single molecule, of anti
      inflammatory and antioxidant properties as well as to its basic character. The
      reduction of the serum TNF-alpha levels could be one of the possible mechanism(s)
      of action of the compound. Further studies are necessary to establish the direct
      mechanism of action(s) of the drug and to evaluate its long-term efficacy and
      safety.

PMID- 12063095
TI  - A comparison of published head and neck stage groupings in laryngeal cancer using
      data from two countries.
AB  - The combination of T, N, and M classifications into stage groupings is meant to
      facilitate a number of activities including: the estimation of prognosis and the
      comparison of therapeutic interventions among similar groups of cases. We tested
      the UICC/AJCC fifth edition stage grouping and six other TNM-based groupings
      proposed for head and neck cancer for their ability to meet these expectations in
      laryngeal cancer using data from Ontario, Canada, and the area of Southern Norway
      surrounding Oslo. We defined four criteria to assess each grouping scheme: (1)
      the subgroups defined by T, N, and M comprising a given group within a grouping
      scheme have similar survival rates (hazard consistency); (2) the survival rates
      differ among the groups (hazard discrimination); (3) the prediction of cure is
      high (outcome prediction); and (4) the distribution of patients among the groups
      is balanced. We previously identified or derived a measure for each criterion,
      and the findings were summarized using a scoring system. The range of scores was
      from 0 (best) to 7 (worst). The data sets were population-based, with 861 cases
      from Ontario and 642 cases from Southern Norway. Clinical stage assignment was
      used and the outcome of interest was cause-specific survival. Summary scores
      across the seven schemes had similar ranges: 0.9 to 5.1 in Ontario and 1.8 to 5.7
      in Southern Norway, but the ranking varied. Summing the scores across the two
      datasets, the TANIS-7 scheme (Head & Neck 1993;15:497-503) ranked first, and was
      ranked high in both datasets (first and second, respectively). The UICC/AJCC
      scheme ranked sixth out of seven schemes, and its ranking was fifth and seventh,
      respectively. UICC/AJCC stage groupings were defined without empirical
      investigation. When tested, this scheme did not perform best. Our results suggest
      that the usefulness of the TNM system could be enhanced by optimizing the design
      of stage groupings through empirical investigation.

PMID- 12063096
TI  - Citation of randomized evidence in support of guidelines of therapeutic and
      preventive interventions.
AB  - Guideline statements may be supported by evidence obtained from various study
      designs, but randomized trials are usually considered most important for making
      recommendations about therapeutic and preventive interventions. This study
      evaluated the extent to which randomized trials are cited in guidelines published
      in major journals. The references of 191 guidelines of therapeutic and/or
      preventive interventions published in Annals of Internal Medicine, BMJ, JAMA,
      Lancet, NEJM and Pediatrics in 1979, 1984, 1989, 1994, and 1999, were analyzed.
      The percentage of guidelines not citing any randomized controlled trials (RCTs)
      decreased gradually from 95% in 1979 to 53% in 1999. Among 4,853 references of
      the guidelines, there were 393 RCTs (8.1% of total), 19 systematic reviews
      (0.4%), and 23 meta-analyses of RCTs (0.5%). Among 19 guidelines published in
      1999 or 1994 with <2 RCTs cited, in eight cases additional pertinent RCTs were
      identified that had not been cited by the guideline. There is a clear increase in
      the use of randomized evidence by guidelines over time. However, several
      guidelines in major journals still cite few or no RCTs.

PMID- 12063097
TI  - Feather bedding and house dust mite sensitization and airway disease in
      childhood.
AB  - Feather bedding has been inversely associated with child wheeze and also with
      house dust mite (HDM) allergen levels. We conducted a cross-sectional analysis of
      the childhood component of a birth cohort study. Our aim was to examine the
      relation between feather bedding and HDM sensitization and airway disease. A
      total of 498 children (84% of eligible) residing in Northern Tasmania in 1997 who
      were eligible for the Tasmanian Infant Health Survey at birth in 1988 or 1989
      participated. Outcome measures included atopic sensitization to Dermatophagoides
      farinae or Dermatophagoides pteronyssinus allergens, spirometric lung function,
      and child respiratory symptoms using questions from the ISAAC study. HDM
      sensitization was strongly associated with frequent wheeze (more than 12 episodes
      of wheeze compared with no wheeze in the past year) (rate ratio [RR], 19.61;
      confidence interval [CI], 6.94-55.56) but only weakly associated with asthma ever
      (RR, 1.65; CI, 1.30-2.09). Feather quilt use was associated with reduced HDM
      sensitization (adjusted RR [ARR], 0.60; CI, 0.45-0.80) and also reduced frequent
      wheeze episodes over the past year (ARR, 0.24; CI, 0.07-0.86). The reduction in
      wheeze was more evident among HDM-sensitized children. These findings are
      consistent with the possible mechanisms for feather bedding of a reduction in
      initial HDM sensitization and an improvement in respiratory symptoms among HDM
      sensitized children. However, prospective studies are required to fully exclude
      selection bias.

PMID- 12063098
TI  - A predictive model for mortality of bloodstream infections. Bedside analysis with
      the Weibull function.
AB  - This paper describes the construction and validation of a prognostic model for
      predicting post-bloodstream infection survival up to Day 21. A Weibull multiple
      regression model was adopted in a prospective cohort study of all patients
      diagnosed with true bacteremia or fungemia in a teaching hospital between 1991
      and 1994 (training set, 1,577 patients). The final model included six variables
      easily detected in any institution: source of infection, underlying neoplasm,
      septic shock, community-acquired, age over 65, and polymicrobial bacteremia.
      Using this model, it is possible to obtain a graphic representation of survival
      probability for any combination of these risk factors. The model was tested on a
      second set of patients diagnosed in the same hospital between 1996 and 1997
      (validation set, 952 patients), confirming its reliability in predicting
      survival. In conclusion, the Weibull function, together with variables easily
      identified at bedside, enables a precise prediction of the short-term, post
      bloodstream infection mortality of a given patient.

PMID- 12063099
TI  - Measuring potentially avoidable hospital readmissions.
AB  - The objectives of this study were to develop a computerized method to screen for
      potentially avoidable hospital readmissions using routinely collected data and a
      prediction model to adjust rates for case mix. We studied hospital information
      system data of a random sample of 3,474 inpatients discharged alive in 1997 from
      a university hospital and medical records of those (1,115) readmitted within 1
      year. The gold standard was set on the basis of the hospital data and medical
      records: all readmissions were classified as foreseen readmissions, unforeseen
      readmissions for a new affection, or unforeseen readmissions for a previously
      known affection. The latter category was submitted to a systematic medical record
      review to identify the main cause of readmission. Potentially avoidable
      readmissions were defined as a subgroup of unforeseen readmissions for a
      previously known affection occurring within an appropriate interval, set to
      maximize the chance of detecting avoidable readmissions. The computerized
      screening algorithm was strictly based on routine statistics: diagnosis and
      procedures coding and admission mode. The prediction was based on a Poisson
      regression model. There were 454 (13.1%) unforeseen readmissions for a previously
      known affection within 1 year. Fifty-nine readmissions (1.7%) were judged
      avoidable, most of them occurring within 1 month, which was the interval used to
      define potentially avoidable readmissions (n = 174, 5.0%). The intra-sample
      sensitivity and specificity of the screening algorithm both reached approximately
      96%. Higher risk for potentially avoidable readmission was associated with
      previous hospitalizations, high comorbidity index, and long length of stay; lower
      risk was associated with surgery and delivery. The model offers satisfactory
      predictive performance and a good medical plausibility. The proposed measure
      could be used as an indicator of inpatient care outcome. However, the instrument
      should be validated using other sets of data from various hospitals.

PMID- 12063100
TI  - Estimating the contribution of individual risk factors to disease in a person
      with more than one risk factor.
AB  - Various measures have been proposed to express the excess risk of an outcome
      attributable to one particular risk factor, such as attributable risk and risk
      fraction. However, there is sometimes a need, both in epidemiological studies and
      in awarding compensation in legal cases, to simultaneously consider the
      contribution of several risk factors to a disease outcome, when a biological
      model is not available. We propose a method that allocates the proportional
      contribution of several risk factors to a disease outcome, based on the weighted
      contribution of the risk fraction for each risk factor. We demonstrate the use of
      this method using figures for renal cell carcinoma, and discuss the caveats in
      using this method for epidemiologic studies, and in awarding compensation in
      legal cases.

PMID- 12063101
TI  - Coronary disease surveillance in Olmsted County objectives and methodology.
AB  - The community surveillance study of coronary heart disease (CHD) in Olmsted
      County, MN, is designed to estimate trends in myocardial infarction (MI)
      incidence, case fatality rate, and CHD mortality, while including all ages. A
      distinctive feature of this study is its ability to capture longitudinal data
      before and after index events via the medical record linkage system of the
      Rochester Epidemiology Project. The goal of this report is to describe the
      methods implemented to measure CHD trends, the implications of including elderly
      individuals on MI ascertainment and trends in prior CHD among persons with
      incident MI. The methods are based on standardized criteria involving the review
      of death certificate information and hospital records to identify CHD deaths, and
      incident MIs in Olmsted County. The medical record linkage system in place under
      the auspices of the Rochester Epidemiology Project was used to ascertain
      antecedent CHD and outcomes. Hospitalized MIs were screened from sampled events
      coded ICD9 codes 410-414 and classified using enzyme values, cardiac pain, and
      ECG coding. After screening 5,042 records, a cohort of 1,658 validated incident
      MIs was assembled 35% (575) among persons aged 75 years or greater. The
      proportion of MIs validated with cardiac pain and enzymes without Minnesota ECG
      coding was lower among the elderly than among persons less than 75 years of age
      (35 vs. 29%, respectively; P <.001). The proportion of events validated without
      requiring ECG coding decreased over time in both age strata (P for trend.001).
      Reliability analyses indicated excellent agreement in event classification. More
      than half of the incident MIs did not have antecedent CHD, and this proportion
      increased overtime. These data indicate that the elderly contribute approximately
      one-third of the cases of incident MI, underscoring the importance of including
      all ages to fully characterize the burden of CHD. Cases among elderly persons
      more frequently require ECG coding for validation, but standardized ascertainment
      procedures are feasible and reliable in all age groups. More than half of the
      incident MIs occurred among persons with no prior CHD, and this proportion
      increased over time. The combination of standardized methodology and of the
      longitudinal data via the record linkage system of the Rochester Epidemiology
      Project will allow reliable measures of CHD trends and help define preventive
      strategies.

PMID- 12063102
TI  - Predictive value of stroke and transient ischemic attack discharge diagnoses in
      The Danish National Registry of Patients.
AB  - We examined the predictive value of the discharge diagnoses of stroke and
      transient ischemic attack (TIA) in The National Registry of Patients (NRP) for
      participants in the Danish cohort study "Diet, Cancer, and Health." We retrieved
      all probable incident registered cases of stroke and TIA, i.e., ICD-10: I60-69.8,
      or G45 (n = 581) within the cohort from the NRP. Medical records and hospital
      discharge summaries were retrieved and reviewed using a standardized form.
      Overall, 299 of 377 cases (79.3%, 95% CI: 74.9-83.3%) of stroke recorded were
      confirmed. Subarachnoidal hemorrhage and intracerebral hemorrhage were confirmed
      in 14 of 29 cases (48.3%, 95% CI: 29.4-67.5%), and 23 of 35 cases (65.7%, 95% CI:
      47.8-80.9%), respectively. By contrast, ischemic stroke and unspecified stroke
      were confirmed in 99 of 113 cases (87.6%, 95% CI: 80.1-93.1%) and 152 of 200
      cases (76.0%, 95% CI: 69.5-81.7%), respectively. Among 134 patients with a TIA
      discharge diagnosis, 60.4% (95% CI: 51.6-68.8%) were confirmed. Discharge
      diagnoses from emergency rooms had lower overall predictive value (48.8%, 95% CI:
      39.9-57.8%) than discharge diagnoses from departments of internal medicine
      (68.8%, 95% CI: 61.3-75.5%) and departments of neurology or neurosurgery (77.9%,
      95% CI: 72.3-82.7%). We conclude that stroke and TIA diagnoses in NRP should be
      used with caution in epidemiological research because the low predictive value
      for some diagnostic subgroups may lead to serious misclassification and biased
      results.

PMID- 12063103
TI  - Measuring agreement between patient and proxy responses to multidimensional
      health-related quality-of-life measures in clinical trials. An application of
      psychometric profile analysis.
AB  - When patients cannot provide responses to health-related quality-of-life (HRQOL)
      measures in clinical trials, family or friends may be asked to respond. We
      present a simple, comprehensive method for assessing agreement between patients
      with head injury and their proxy responders. In contrast to more traditional
      approaches, this method defines agreement separately for each patient-proxy pair,
      and compares HRQOL profiles along three dimensions-level, or the average of the
      ratings; scatter, or the variability in the ratings; and shape, or the ranks of
      the ratings. We demonstrate this method in the context of a clinical trial of a
      treatment for traumatic head injury and compare the results to those obtained
      using traditional analyses. Options for incorporating proxy responses into
      clinical trial analyses are discussed.

PMID- 12063104
TI  - Standardized retrieval of side effects data for meta-analysis of safety outcomes.
      A feasibility study in acute sinusitis.
AB  - Accurate and complete safety data are indispensable for the proper evaluation of
      the benefit-to-harm ratio of medical interventions. We evaluated whether a
      systematic review and meta-analysis of standardized safety data is feasible by
      requesting information on side effects directly from the investigators of all 38
      antibiotic trials on acute sinusitis published in the last decade. We requested
      standardized information on gastrointestinal toxicity outcomes, including
      hospitalizations, discontinuations, and days with nausea/vomiting, diarrhea, or
      both. Responses were received only for 16 trials (42%), and safety data were
      contributed only for 9 trials (24%). In some trials, safety data had not been
      collected, had been lost, or had been transferred to other companies. The odds of
      data retrieval was higher in general medical journals (P =.024) and independently
      improved with an increase in sample size (P =.064). The available information
      suggested side effects may equal or exceed in severity the marginal treatment
      benefits. Interpretation of safety data was further complicated by heterogeneity
      or lack of information of use of concomitant drugs, mode of collection of safety
      information, use of blinding, and other study design parameters. Availability of
      standardized information for performing meta-analysis of safety data may be
      limited. Standardized reporting, prospective collection, and long-term
      availability of safety information should be improved.

PMID- 12063116
TI  - Interactions of different phenolic acids and flavonoids with soy proteins.
AB  - Soy glycinin (SG) and soy trypsin inhibitor (STI) were derivatized by chlorogenic
      and caffeic acid (cinnamic acids, C(6)-C(3) structure), and by gallic acid
      representing hydroxybenzoic acids (C(6)-C(1) structure). Further, the flavonoids,
      flavone, apigenin, kaempferol, quercetin and myricetin (C(6)-C(3)-C(6) structure)
      were also caused to react with soy proteins to estimate the influence of the
      number and the position of hydroxy substituents. The derivatization caused a
      reduction of lysine, cysteine and tryptophan residues in the soy proteins. The
      isoelectric points of the derivatives were shifted to lower pH values and
      formation of high molecular fractions was documented. The derivatives were
      characterized in terms of their solubility at different pH-values to document the
      influence on the functional properties. The structural changes induced were
      studied using circular dichroism (CD), differential scanning calorimetry (DSC),
      intrinsic fluorescence, and binding of anilinonaphthalenesulfonic acid. The
      influence of derivatization on the in-vitro digestibility with trypsin,
      chymotrypsin, pepsin and pancreatin was also assessed. The effect on the trypsin
      inhibitor activity of all the resulting STI derivatives was studied, the latter
      being reduced.

PMID- 12063117
TI  - Effect of heparin chain length on the interaction with tissue factor pathway
      inhibitor (TFPI).
AB  - Tissue factor pathway inhibitor (TFPI) is a heparin-binding protein involved in
      the extrinsic blood coagulation system. In order to elucidate the minimal size of
      heparin chain required for the interaction with TFPI, we prepared a series of
      heparin-derived oligosaccharides with tailored chain length ranged from
      disaccharide to eicosasaccharide after the successive treatments of heparin,
      including partial N-desulphation, deaminative cleavage with nitrous acid and gel
      filtration. Affinity chromatography study of each oligosaccharide fraction using
      TFPI as the ligand indicated that increasing the degree of polymerisation causes
      increased affinity, and that a remarkable change in the affinity occurs between
      the decamers and dodecamers. Measurement of factor Xa inhibitory activity of TFPI
      in the presence of each oligosaccharide fraction indicated that the fractions
      shorter than dodecamers only slightly enhanced the TFPI activity for factor Xa
      inhibition, while the fractions larger than octadecamers had an effect comparable
      to full-length heparin. These were compatible to the results from the kinetic
      analyses of the interaction between TFPI and heparin-derived oligosaccharide with
      an evanescent wave-based biosensor system, IAsys, using a TFPI C-terminal peptide
      as the ligand.

PMID- 12063118
TI  - Kinetics of chaperoning of dithiothreitol-denatured alpha-lactalbumin by alpha
      crystallin.
AB  - Molecular chaperones prevent the aggregation of partially folded or misfolded
      forms of protein. alpha-Crystallin performs such a function in the ocular lens.
      Dynamic light scattering (DLS) measurements were performed to gain insight into
      the kinetics and mechanism of alpha-crystallin chaperoning. Experiments were
      conducted as a function of alpha-lactalbumin concentration as well as the alpha
      crystallin/alpha-lactalbumin ratio over a 24 h period. In the particle
      distribution patterns the lactalbumin concentration was partitioned into three
      compartments: (a) monomeric free lactalbumin; (b) lactalbumin in the chaperoning
      complex; and (c) lactalbumin aggregates. DLS intensities were converted to molar
      concentrations by assuming a model of a spherical chaperoning complex. In the
      model, alpha-crystallin is the central core and alpha-lactalbumin molecules
      occupy a ring surrounding the core. The kinetics of chaperoning was studied by
      proposing a simple scheme with four rate constants. The reversible reaction of
      the formation of the chaperoning complex is characterized by rate constants k(1)
      and k(2). The rate constants k(3) and k(4) govern the irreversible aggregation of
      lactalbumin: the former from the free monomeric lactalbumin pool and the latter
      describing the aggregation of the denatured lactalbumin released from the
      chaperoning complex. The rate constants, k(3) and k(4) are four magnitudes larger
      than k(1) and k(2). The equilibrium constant of chaperoning complex formation
      lies in favor of the reactants. k(4) is somewhat faster than k(3) and it is three
      times faster than k(s) governing the self-aggregation of lactalbumin in the
      absence of alpha-crystallin.

PMID- 12063119
TI  - Bilirubin binding properties of pigeon serum albumin and its comparison with
      human serum albumin.
AB  - Binding of bilirubin (BR) to pigeon serum albumin (PgSA) was studied by
      absorption, fluorescence and CD spectroscopy and results were compared with those
      obtained with human serum albumin (HSA). PgSA was found to be structurally
      similar to HSA as judged by near- and far-UV CD spectra. However, PgSA lacks
      tryptophan. Binding of BR to PgSA showed relatively weaker interaction compared
      to HSA in terms of binding affinity, induced red shift in the absorption spectrum
      of BR and CD spectral characteristics of BR-albumin complexes. Photoirradiation
      results of BR-albumin complexes also showed PgSA-bound BR more labile compared to
      HSA-bound BR.

PMID- 12063120
TI  - Viscosity of alpha-crystallin solutions.
AB  - Accommodation in the mammalian lens requires flexure of lens fibres and some
      redistribution of their contents involving limited viscous flow. Shear-dependent
      viscosity of bovine alpha-crystallin solutions was determined with the Contraves
      Low-Shear Rheometer between 4.4 and 347 mg ml(-1), and at 15.5, 25, 30, and 37
      degrees C. All solutions showed significant shear thinning, with markedly higher
      viscosity at physiological levels of approximately 300 mg ml(-1). Viscosity
      concentration graphs were similar at low (1.0 s(-1)) and high (94.5 s(-1)) shear
      rates, indicating low molecular interaction in solution. Arrhenius plots which
      might have indicated the size of the energy barrier to displacement of molecules
      or aggregates were inconclusive.

PMID- 12063121
TI  - Activity and conformation of a cyclic heptapeptide possessing the message
      sequence His-Phe-Arg-Trp of alpha-melanotropin.
AB  - Alpha-melanotropin (alpha-MSH, i.e. alpha-melanocyte stimulating hormone),
      tridecapeptide (Ac-Ser(1)-Tyr-Ser-Met-G1u(5)-His-Phe-Arg-Trp-Gly(10)-Lys-Pro
      Val(13)-NH(2)), has been extensively studied to understand structure-activity
      relationships. The core sequence (His-Phe-Arg-Trp) is conserved in several
      species and is considered as the primary active site or "message sequence".
      Attempts have been made to design conformationally constrained cyclic analogs
      containing the message sequence to improve the activity. We had earlier reported
      that the cyclic analog--cyclo[Gly-His-D-Phe-Arg-Trp-Gly], a 18 membered ring
      system with two fused beta-turn structure, was less active than the corresponding
      linear peptide. It was suggested that ring size could be an important parameter
      in the activity of cyclic melanotropic analogs. To investigate the effect of ring
      size on biological activity, a cyclic heptapeptide, cyclo[Nle(1)-Gly-His-D-Phe
      Arg(5)-Trp-Gly(7)], with 21 member ring system was synthesized. This peptide has
      three orders of magnitude higher biological activity than the cyclic hexapeptide.
      The conformational study of this cyclic heptapeptide in DMSO-d(6) by NMR and
      molecular dynamics simulations reveals a structure with two fused beta-turns
      running across the residues D-Phe(4)-Gly(7) (Type I) and Gly(7)-His(3) (Type II).
      These findings confirm that stabilization of beta-turns and a relatively larger
      ring size are essential determinants of activity for cyclic alpha-MSH analogs.

PMID- 12063122
TI  - Novel plasma-separation dilayer gellan-gellan-sulfate adsorber for direct removal
      of extra domain A containing fibronectin from the blood of rheumatoid arthritis
      patients.
AB  - Rheumatoid arthritis (RA) patients, in whom cryogelation occurs in the presence
      of heparin, exhibit abnormally high concentrations of extra domain A containing
      fibronectin [EDA(+)FN] in their plasma. The selective removal of EDA(+)FN from
      patient blood is therefore of potential therapeutic benefit. Gellan-sulfate is a
      candidate ligand for the removal of EDA(+)FN due to its high affinity for FN. In
      this study, we prepare a novel adsorber for the direct removal of EDA(+)FN from
      patient blood. The adsorber has both a plasma separation function and EDA(+)FN
      trapping zones, and is prepared by cross-linking gellan-sulfate with
      epichlorohydrine. The ratio of gellan-sulfate to gellan in the adsorber is 48%.
      The surface and internal structure of gellan beads were observed by a range of
      microscopic techniques, and the beads were found to have a dilayer structure,
      consisting of a porous outer layer and an underlying gellan-sulfate phase as the
      adsorber. The affinity constants of the gellan-sulfate beads for EDA(+)FN were
      almost the same in blood as in buffer because the porous gellan coating acts to
      separate plasma from the cellular fraction of the blood. The removal rate of
      plasma proteins and blood cells from mock RA blood was measured for coated and
      uncoated gellan-sulfate beads. Removal rates were 30-32% for EDA(+)FN, 6-10% for
      fibrinogen, 10-14% for antithrombin III, 8% for C3, 4-7% for C4, and 0% for
      albumin. The removal rates of uncoated beads were 11% for white blood cells, 0%
      for red blood cells and 33% for platelets, whereas removal rates of 0% for white
      blood cells, 0% for red blood cells and 20% for platelets were achieved for
      coated beads. The coating effectively inhibits the adsorption of white blood
      cells and platelets. Existing problems with direct adsorbers, including
      selectivity and plasma separation, have been solved by this material.

PMID- 12063123
TI  - Specific interactions between cryogel components: role of extra domain A
      containing fibronectin in cryogelation.
AB  - Cryogel is a physical gel formed by heterophilic aggregation of extra domain A
      containing fibronectin [EDA(+)FN], plasma fibronectin (pFN), fibrinogen (Fbg) and
      heparin (Hep), which are found in high concentrations in the blood of patients
      suffering from rheumatoid arthritis. In this study, we clarify the specific
      interactions between cryogel components in terms of the affinity constant (K(A)),
      obtained by surface plasmon resonance (SPR). It is found that Fbg self
      interactions occur at lower temperatures, and that K(A) of Fbg-Hep changes with
      temperature. Specifically, K(A) (2.0 x 10(8) [M(-1)]) of Fbg-Hep at 5 degrees C
      increases significantly from that (1.0x10(7) [M(-1)]) at 40 degrees C. K(A) of
      EDA(+)FN-Hep increases with temperature, by approximately 100-fold between 40
      degrees C (K(A)=10(12) [M(-1)]) and 20 degrees C (K(A)=10(10) [M(-1)]). Although
      K(A) of the FN fragments of Hep-binding domain containing an EDA region
      [EDA(+)HBD(+)] and Hep increases with temperatures above 30 degrees C, K(A)s of
      HBD(+)-Hep and EDA(+)-Hep are not temperature-dependent. Therefore, EDA(+)HBD(+),
      formed as a special structure for high Hep affinity, exhibits temperature
      dependent interaction with Hep. These results suggest that the main role of
      EDA(+)FN in cryogelation is to support the interaction with Hep.

PMID- 12063124
TI  - Proceedings of the 2nd Annual Multisensory Research Conference. October 2000,
      Tarrytown, New York, USA.

PMID- 12063125
TI  - Tool-use learning selectively induces expression of brain-derived neurotrophic
      factor, its receptor trkB, and neurotrophin 3 in the intraparietal
      multisensorycortex of monkeys.
AB  - When humans repeatedly use a tool, our body image alters until the tool finally
      becomes a part or an extension of the body. This alteration of body image perhaps
      results from re-integration of somatosensory and visual signals. We trained
      Japanese monkeys to use a rake-shaped tool to retrieve a distant food pellet,
      then used a novel tissue-sampling method to suction brain tissue from the
      anterior bank of their intraparietal sulcus, where somatosensory and visual
      signals converge. Examination of the messenger RNA expression levels of
      neurotrophins and their receptors using real-time quantitative polymerase chain
      reaction revealed learning-selective induction in the expression of brain-derived
      neurotrophic factor, its receptor trkB, and NT-3 during, but not after, the
      learning. These results suggest that these factors are involved in the
      reorganization of the somatosensory and visual signals in the anterior bank of
      the intraparietal sulcus when monkeys are learning the use of the tool.

PMID- 12063126
TI  - Multimodality in the superior colliculus: an information theoretic analysis.
AB  - The deep superior colliculus (DSC) integrates multisensory input and triggers an
      orienting movement toward the source of stimulation (target). It would seem
      reasonable to suppose that input of an additional modality should always increase
      the amount of information received by a DSC neuron concerning a target. However,
      of all DSC neurons studied, only about one half in the cat and one-quarter in the
      monkey were multimodal. The rest received only unimodal input. Multimodal DSC
      neurons show the properties of multisensory enhancement, in which the neural
      response to an input of one modality is augmented by input of another modality,
      and of inverse effectiveness, in which weaker unimodal responses produce a higher
      percentage enhancement. Previously, we demonstrated that these properties are
      consistent with the hypothesis that DSC neurons use Bayes' rule to compute the
      posterior probability that a target is present given their stochastic sensory
      inputs. Here we use an information theoretic analysis of our Bayesian model to
      show that input of an additional modality may indeed increase target information,
      but only if input received from the initial modality does not completely reduce
      uncertainty concerning the presence of a target. Unimodal DSC neurons may be
      those whose unimodal input fully reduces target uncertainty and therefore have no
      need for input of another modality.

PMID- 12063127
TI  - Early auditory-visual interactions in human cortex during nonredundant target
      identification.
AB  - A common finding of behavioral studies is that objects characterized by redundant
      multisensory cues are identified more rapidly than the same objects presented in
      either unimodal condition. In a previous electrophysiological study in humans, we
      have described a network of crossmodal interactions that could be associated with
      this facilitation effect [M.H. Giard, F. Peronnet, J. Cogn. Neurosci. 11(5)
      (1999) 473-490]. Here, we sought to determine whether the recognition of objects
      characterized by nonredundant bimodal components may still induce crossmodal
      neural interactions. Subjects had to identify three objects defined either by
      auditory or visual features alone, or by the combination of nonredundant auditory
      and visual features. As expected, behavioral measures showed no sign of
      facilitation in bimodal processing. Yet, event-related potential analysis
      revealed the existence of early (<200 ms latency) crossmodal activities in
      sensory-specific and nonspecific cortical areas, that were partly dependent on
      the sensory dominance of the subjects to perform the task. Comparative analysis
      of the interaction patterns involved in redundant and nonredundant cue processing
      provides evidence for the robustness of the principle of crossmodal neural
      synergy that applies whatever the stimulus content (redundant or nonredundant
      information), and for the high flexibility of the neural networks of integration
      that are sensitive both to the nature of the perceptual task and to the sensory
      skill of the individual in that particular task.

PMID- 12063128
TI  - On the neuronal basis for multisensory convergence: a brief overview.
AB  - For multisensory stimulation to effect perceptual and behavioral responses,
      information from the different sensory systems must converge on individual
      neurons. A great deal is already known regarding processing within the separate
      sensory systems, as well as about many of the integrative and
      perceptual/behavioral effects of multisensory processing. However, virtually
      nothing is known about the functional architecture that underlies multisensory
      convergence even though it is an integral step to this processing sequence. This
      paper seeks to summarize the findings pertinent to multisensory convergence, and
      to initiate the identification of specific convergence patterns that may underlie
      different multisensory perceptual and behavioral effects.

PMID- 12063129
TI  - Heterogeneity and heterochrony in the development of intersensory perception.
AB  - It is now well established that a variety of intersensory perceptual skills
      emerge in early human development. Empirical evidence from studies in the
      author's as well as other laboratories charting the developmental emergence of
      these abilities is reviewed. The evidence is considered in terms of the currently
      dominant theoretical view of intersensory development that assigns the detection
      of amodal invariants a primary and foundational role. It is argued that this view
      is inadequate because the detection of amodal invariants is only one of three
      distinct intersensory integration processes. It is noted that the other two
      processes, namely, intersensory association of modality-specific cues and non
      specific effects of stimulation in one modality on responsiveness to stimulation
      in another modality, are equally important and that the operation of all three
      and, in particular, the relation between them, must be studied to attain a
      complete understanding of intersensory perceptual development. It is suggested
      that the theoretical approach to the development of intersensory perception
      should be broadened to include all three types of processes and that
      developmental studies must respect basic facts and principles of development. To
      this end, a developmental systems approach is proposed that holds that the
      development of intersensory integration consists of the heterochronous emergence
      of heterogeneous perceptual skills.

PMID- 12063130
TI  - Auditory and visual attention modulate motion processing in area MT+.
AB  - Behavioral and physiological studies have established that visual attention to a
      given feature or location can modulate early visual processing. In the present
      experiment, we asked whether auditory attention can likewise influence visual
      processing. We used a visual illusion, the motion aftereffect (MAE), to assess
      the effects of visual and auditory attention on motion processing in human area
      MT+. We acquired psychophysical and functional magnetic resonance imaging (fMRI)
      data while subjects fixated and viewed moving and stationary stimuli in
      alternating blocks. For each of four motion conditions, we measured the duration
      of the subsequent MAE, the time for activity in MT+ to return to baseline after
      motion adaptation (decay time), and the magnitude of MT+ activity during motion
      adaptation. For each subject, we first obtained measures of motion processing in
      the absence of attentional demands, by comparing reversing and expanding motion
      conditions. Subjects perceived the MAE following adaptation to expanding but not
      reversing motion, as observed previously, and decay times in MT+ were selectively
      prolonged after expanding motion. We then assessed the effects of performing
      either a visual or an auditory attentional task during expanding motion
      adaptation. Performance of the attentional task, whether visual or auditory,
      produced a significant reduction of subsequent MAE perception and associated
      decay times in MT+, as compared to expanding motion with fixation only. Both
      attentional tasks also reduced the magnitude of activation during motion
      adaptation. These data show that auditory attention, like visual attention, can
      modify sensory processing at a remarkably early stage of the visual hierarchy.

PMID- 12063131
TI  - Multisensory processing in the elaboration of place and head direction responses
      by limbic system neurons.
AB  - This review explores the roles of several sensory modalities in the establishment
      and maintenance of discharges correlated with head position and orientation in
      neurons of the hippocampus and associated structures in the Papez circuit. Focus
      is placed on the integration of signals related to environmental cues and to
      displacement movements, both of external and internal origin. While the visual,
      vestibular and motor systems each exert influences, position and head direction
      signals are nevertheless maintained in the absence of any one of these respective
      inputs. Context-related changes in hippocampal discharge correlates are also
      highlighted. These characteristics provide these signals with robustness and
      flexibility, properties particularly suited for cognitive processes such as
      contextual processing, memory and planning.

PMID- 12063132
TI  - Mental rotation of tactile stimuli.
AB  - When subjects decide whether two visual stimuli presented in various orientations
      are identical or mirror-images, reaction time increases with the angular
      disparity between the stimuli. The interpretation of this well-known observation
      is that subjects mentally rotate images of the stimuli until they are in
      congruence, in order to solve the task. Here we review studies involving mental
      rotation of tactile stimuli. Mental rotation in tactile tasks is specifically
      associated with the requirement for mirror-image discrimination, as opposed to
      identity judgments. The key brain region mediating mental rotation of tactile
      stimuli seems to be the parietal cortex. Visual processing appears to facilitate
      task performance. We report an experiment from our laboratory addressing the
      nature of the reference frame for mental rotation of tactile stimuli. Our
      observations indicate that when the hand is directly in front of the body, with
      the head facing forward, the shortest reaction times for mirror-image
      discrimination of stimuli applied to the fingerpad are obtained when the
      longitudinal axis of the stimulus is in or parallel to the sagittal plane, even
      when this is perpendicular to the long axis of the finger. Thus, the reference
      frame for mental rotation of tactile stimuli is not purely hand-centered. This is
      consistent with other findings indicating variable assignment of reference frames
      for tactile perception.

PMID- 12063133
TI  - Facial expressions modulate the time course of long latency auditory brain
      potentials.
AB  - Long latency auditory brain potentials were recorded while subjects listened to
      bi-syllabic words spoken with an emotional expression and concurrently viewed
      congruent or incongruent facial expressions. Analysis of the auditory waveforms
      suggests the existence of a positive deflection around 240 ms post-stimulus with
      a clear posterior topography (the P2b component). This potential is subsequent
      upon the modality-specific auditory N1-P2 components and precedes the amodal N2
      P3 complex. Congruent face-voice trials elicited an earlier P2b component than
      incongruent trials suggesting that auditory processing is delayed in the presence
      of an incongruent facial context. These electrophysiological results are
      consistent with previous behavioural studies showing an acceleration of reaction
      times for rating voice expressions that are part of congruent bimodal stimulus
      pairs. A source localisation analysis performed on the scalp EEG during the time
      window corresponding to the P2b component disclosed a single dipole solution in
      the anterior cingulate cortex.

PMID- 12063134
TI  - An analysis of audio-visual crossmodal integration by means of event-related
      potential (ERP) recordings.
AB  - Crossmodal integration was studied in humans by presenting random sequences of
      auditory (brief noise bursts), visual (flashes), and audiovisual (simultaneous
      noise bursts and flashes) stimuli from a central location at irregular intervals
      between 600 and 800 ms. The subjects' task was to press a button to infrequent
      and unpredictable (P=0.15) target stimuli that could be either a more intense
      noise burst, a brighter flash, or a combination of the two. In accordance with
      previous studies, behavioral data showed that bimodal target stimuli were
      responded to much faster and were identified more accurately than the unimodal
      target stimuli. The neural basis of this crossmodal interaction was investigated
      by subtracting the ERPs to the auditory (A) and the visual (V) stimuli alone from
      the ERP to the combined audiovisual (AV) stimuli (i.e. interaction=AV-(A+V)).
      Using this approach, we replicated previous reports of both early (at around 40
      ms) and late (after 100 ms) ERP interaction effects. However, it appears that the
      very early interaction effects can be largely accounted for by an anticipatory
      ERP that precedes both the unimodal and bimodal stimuli. In calculating the ERP
      interaction this slow shift is subtracted twice, resulting in an apparent shift
      of the opposite polarity that may be confounded with actual crossmodal
      interactions.

PMID- 12063135
TI  - Multisensory auditory-visual interactions during early sensory processing in
      humans: a high-density electrical mapping study.
AB  - Integration of information from multiple senses is fundamental to perception and
      cognition, but when and where this is accomplished in the brain is not well
      understood. This study examined the timing and topography of cortical auditory
      visual interactions using high-density event-related potentials (ERPs) during a
      simple reaction-time (RT) task. Visual and auditory stimuli were presented alone
      and simultaneously. ERPs elicited by the auditory and visual stimuli when
      presented alone were summed ('sum' ERP) and compared to the ERP elicited when
      they were presented simultaneously ('simultaneous' ERP). Divergence between the
      'simultaneous' and 'sum' ERP indicated auditory-visual (AV) neural response
      interactions. There was a surprisingly early right parieto-occipital AV
      interaction, consistent with the finding of an earlier study [J. Cogn. Neurosci.
      11 (1999) 473]. The timing of onset of this effect (46 ms) was essentially
      simultaneous with the onset of visual cortical processing, as indexed by the
      onset of the visual C1 component, which is thought to represent the earliest
      cortical visual evoked potential. The coincident timing of the early AV
      interaction and C1 strongly suggests that AV interactions can affect early visual
      sensory processing. Additional AV interactions were found within the time course
      of sensory processing (up to 200 ms post stimulus onset). In total, this system
      of AV effects over the scalp was suggestive of both activity unique to
      multisensory processing, and the modulation of 'unisensory' activity. RTs to the
      stimuli when presented simultaneously were significantly faster than when they
      were presented alone. This RT facilitation could not be accounted for by
      probability summation, as evidenced by violation of the 'race' model, providing
      compelling evidence that auditory-visual neural interactions give rise to this RT
      effect.

PMID- 12063136
TI  - A comparison of bound and unbound audio-visual information processing in the
      human cerebral cortex.
AB  - Human speech has auditory (heard speech) and visual (seen speech) qualities. The
      neural representation of audiovisual integration in speech was investigated using
      functional magnetic resonance imaging (fMRI). Ten subjects were imaged while
      viewing a face in four different conditions: with speech and mouth movements
      synchronized, with speech and mouth movements desynchronized, during silent
      speech, or while viewing a static face. Subtractions of the different sets of
      images showed that lipreading primarily activated the STG/STS. Synchronized audio
      visual speech and desynchronized audio-visual speech activated similar areas.
      Regions activated more in the synchronized versus the desynchronized conditions
      were considered to be those involved in cross-modal integration. One dominant
      activation focus was found near the left claustrum, a subcortical region. A
      region-of-interest analysis of the STS and parietal areas found no difference
      between audio-visual conditions. However, this analysis found that synchronized
      audio-visual stimuli led to a higher signal change in the claustrum region. This
      study extends previous results, using other sensory combinations, and other
      tasks, indicating involvement of the claustrum in sensory integration.

PMID- 12063137
TI  - The ventriloquist in motion: illusory capture of dynamic information across
      sensory modalities.
AB  - Integrating dynamic information across the senses is crucial to survival.
      However, most laboratory studies have only examined sensory integration for
      static events. Here we demonstrate that strong crossmodal integration can also
      occur for an emergent attribute of dynamic arrays, specifically the direction of
      apparent motion. The results of the present study show that the perceived
      direction of auditory apparent motion is strongly modulated by apparent motion in
      vision, and that both spatial and temporal factors play a significant role in
      this crossmodal effect. We also demonstrate that a split-brain patient who does
      not perceive visual apparent motion across the midline is immune to this
      audiovisual dynamic capture effect, highlighting the importance of motion being
      experienced in order for this new multisensory illusion to occur.

PMID- 12063138
TI  - Visual illusion induced by sound.
AB  - We present the first cross-modal modification of visual perception which involves
      a phenomenological change in the quality-as opposed to a small, gradual, or
      quantitative change-of the percept of a non-ambiguous visual stimulus. We report
      a visual illusion which is induced by sound: when a single flash of light is
      accompanied by multiple auditory beeps, the single flash is perceived as multiple
      flashes. We present two experiments as well as several observations which
      establish that this alteration of the visual percept is due to cross-modal
      perceptual interactions as opposed to cognitive, attentional, or other origins.
      The results of the second experiment also reveal that the temporal window of
      these audio-visual interactions is approximately 100 ms.

PMID- 12063139
TI  - Confusing the mind by crossing the hands.
AB  - Observers made temporal order judgements (TOJs) regarding which of two tactile
      stimuli presented to either hand (at stimulus onset asynchronies of up to 200 ms)
      occurred first. When the observers' hands were placed in an uncrossed posture
      (i.e., each hand in its own hemispace), performance was accurate, with a just
      noticeable difference (JND; the smallest interval which produces 75% correct
      performance) of 34 ms. By contrast, when the hands were crossed over the midline,
      performance declined such that 124 ms was needed for accurate performance. In a
      second experiment, we presented visual instead of tactile stimuli to evaluate the
      relative contribution of motor and perceptual confusions to the effect. While
      performance with crossed hands was significantly worse than with uncrossed hands
      (JND=36 vs. 31 ms, respectively), this difference was negligible compared to that
      with tactile stimuli. In a third experiment, experienced observers showed a
      robust crossed-hands deficit which was not improved by using different fingers on
      either hand. We argue that the decline in tactile discrimination performance when
      the hands are crossed reflects a failure to represent appropriately near
      simultaneous bimanual tactile stimuli, and stands in marked contrast to many
      recent observations of efficient remapping of singly-presented tactile stimuli.

PMID- 12063140
TI  - Multisensory fusion: simultaneous re-weighting of vision and touch for the
      control of human posture.
AB  - We examined the generally held belief that the postural control system is able to
      re-weight its available sensory inputs in order to optimize stance control in
      altered sensory environments. Our view is that previous accounts of sensory re
      weighting provide only indirect evidence, which is subject to alternative
      explanations. The present results provide strong evidence for sensory re
      weighting as the primary mechanism for changes observed in postural sway between
      conditions. Subjects were presented with small-amplitude, oscillatory visual and
      somatosensory stimuli at 0.20 and 0.28 Hz, respectively, in five conditions that
      manipulated the amplitudes of stimulus motion. Gain calculated in each trial with
      respect to each of the two stimuli was found to change systematically as stimulus
      motion amplitudes changed across condition. The observed pattern of gain rules
      out a constant-weight, linear account of posture and is consistent with the re
      weighting hypothesis. Parameter fits of a third-order, linear stochastic model to
      postural sway trajectories in each condition showed that changes in gain across
      condition were primarily due to changes in coupling coefficients rather than
      changes in parameters that characterize the stability of the postural system.
      Visual gain was found to depend upon visual motion amplitude and touch gain was
      found to depend upon touch motion amplitude, indicating intra-modality
      dependencies. Visual gain also depended upon touch motion amplitude, indicating
      an inter-modality dependence. To our knowledge, simultaneous re-weighting of more
      than one sensory input has never been rigorously demonstrated. These techniques
      may be able to resolve the source of balance control deficits across populations
      with far more certainty than currently possible.

PMID- 12063141
TI  - Influence of a sensorimotor conflict on the memorization of a path traveled in
      virtual reality.
AB  - Studies of visual-vestibular and vestibular-proprioceptive interactions suggest
      that prolonged exposure to sensory conflicts induces a modification of the
      relation between sensory modalities for self-motion perception. With most models
      conflicts are solved by a weighting process. However, the brain could also switch
      between conflicting cues. The present study focused on the effect of mismatched
      visual and non-visual information on the reproduction of actively performed
      turns. Standing subjects viewed a virtual corridor in which forward movements
      were simulated at a constant linear velocity, and rotations were actually
      performed. They were asked to learn the trajectory and then to reproduce it from
      memory in total darkness. In the baseline condition, the relative amplitudes of
      visual and non-visual information for the rotations performed were the same, but
      were manipulated in the two 'sensory conflict' conditions. The results show that
      even when subjects did not notice the sensory conflict, the discrepancy between
      visual and non-visual information affected their ability to reproduce the angular
      displacements. In one conflict condition, subjects relied on visual information
      when asked to draw the trajectory traveled, yet reproduced rotations on the basis
      of non-visual information during active blindfolded movements. This dissociation
      suggests that for mental simulation of the same path, there are at least two
      cognitive strategies of memory storage and retrieval, using either visual or non
      visual information, according to the task and the sensory context.

PMID- 12063142
TI  - The timing and laminar profile of converging inputs to multisensory areas of the
      macaque neocortex.
AB  - Two fundamental requirements for multisensory integration are convergence of
      unisensory (e.g. visual and auditory) inputs and temporal alignment of the neural
      responses to convergent inputs. We investigated the anatomic mechanisms of
      multisensory convergence by examining three areas in which convergence occurs,
      posterior auditory association cortex, superior temporal polysensory area (STP)
      and ventral intraparietal sulcus area (VIP). The first of these was recently
      shown to be a site of multisensory convergence and the latter two are more well
      known as 'classic' multisensory regions. In each case, we focused on defining the
      laminar profile of response to the unisensory inputs. This information is useful
      because two major types of connection, feedforward and feedback, have
      characteristic differences in laminar termination patterns, which manifest
      physiologically. In the same multisensory convergence areas we also examined the
      timing of the unisensory inputs using the same standardized stimuli across all
      recordings. Our findings indicate that: (1) like somatosensory input [J.
      Neurophysiol., 85 (2001) 1322], visual input is available at very early stages of
      auditory processing, (2) convergence occurs through feedback, as well as
      feedforward anatomical projections and (3) input timing may be an asset, as well
      as a constraint in multisensory processing.

PMID- 12063143
TI  - Development of an integrated model of personality, personality disorders and
      severe axis I disorders, with special reference to major affective disorders.
AB  - A unidimensional model of the relationships between normal temperament,
      psychopathic variants of it and the two main forms of so-called endogenous
      psychoses (major affective disorders and schizophrenia) was derived from
      Kretschmer's constitutional typology. It was, however, not confirmed by means of
      a biometric approach nor was Kretschmer's broad concept of cyclothymia as a
      correlate of physical stoutness on the one hand and major affective disorders on
      the other supported by empirical data. Yet the concept of the 'melancholic type'
      of personality of patients with severe unipolar major depression (melancholia)
      which resembles descriptions by psychoanalysts could be corroborated. This was
      also true for the 'manic type' of personality as a (premorbid) correlate of
      predominantly manic forms of a bipolar I disorder. As predicted from a spectrum
      concept of major affective disorders, the ratio of traits of either type co
      varied with the ratio of the depressive and the manic components in the long-term
      course of such a disorder. The two types of premorbid personality and a rare
      variant of the 'manic type', named 'relaxed, easy-going type', were conceived as
      'affective types' dominating in major affective disorders. They are opposed to
      three 'neurotoid types' prevailing in so-called neurotic disorders as well as in
      schizophrenic psychoses. The similarity among the types can be visualized as
      spatial relationships in a circular, i.e. a two-dimensional, model (circumplex).
      Personality disorders as maladapted extreme variants of personality are, by
      definition, located outside the circle, mainly along its 'neurotoid' side.
      However, due to their transitional nature, axis I disorders cannot be represented
      adequately within the plane which represents (adapted as well as maladapted)
      forms of habitual behaviour (personality types and disorders, respectively). To
      integrate them into the spatial model of similarity interrelations, a dimension
      of actual psychopathology has to be added to the two-dimensional plane as a third
      (orthogonal) axis. The distance of a case from the 'ground level' of habitual
      behaviour corresponds with the severity of the actual psychopathological state.
      The specific form of that state (e.g. manic or depressive), however, varies along
      one the axes which define the circumplex of habitual behaviour. This three
      dimensional model is, by its very nature, more complex than the unidimensional
      one derived from Kretschmer's typological concept, but it is clearly more in
      accordance with empirical data.

PMID- 12063144
TI  - A meta-(re)analysis of the effects of cognitive therapy versus 'other therapies'
      for depression.
AB  - BACKGROUND: Cognitive therapy (CT) for depression has been found to be
      efficacious for the treatment of depression. In comparison to other
      psychotherapies, CT has been shown to be approximately equal to behavior
      therapies, but sometimes superior to 'other therapies.' The latter comparison is
      problematic given that 'other therapies' contain bona fide treatments as well as
      treatments without therapeutic rationale for depression. METHOD: A meta-analysis
      was conducted for studies that compared CT to 'other therapies' in an earlier
      meta-analysis, except that in this meta-analysis 'other therapies' were
      classified as bona fide and non-bona fide. RESULTS: The benefits of CT were found
      to be approximately equal to the benefits of bona fide non-CT and behavioral
      treatments, but superior to non-bona fide treatments. CONCLUSIONS: The results of
      this study fail to support the superiority of CT for depression. On the contrary,
      these results support the conclusion that all bona fide psychological treatments
      for depression are equally efficacious.

PMID- 12063145
TI  - Mortality of patients with mood disorders: follow-up over 34-38 years.
AB  - BACKGROUND: All follow-up studies of causes of death in affective disordered
      patients have found they have markedly elevated suicide rates and a less
      reproducible increased mortality from other causes. The reported rates by gender,
      disorder type and treatment are more variable. METHODS: Hospitalised affective
      disordered patients (n=406) were followed prospectively for 22 years or more.
      Later, mortality was assessed for 99% of them at which time 76% had died.
      RESULTS: Standardised Mortality Rates (observed deaths/expected deaths) for
      patients were elevated especially for suicide and circulatory disorders in both
      men and women. Women actually had higher suicide rates but that did not take into
      account the twofold increase in general population rates for men. Unipolar
      patients had significantly higher rates of suicide than bipolar Is or IIs. In all
      groups long term medication treatment with antidepressants alone or with a
      neuroleptic, or with lithium in combination with antidepressants and/or
      neuroleptics significantly lowered suicide rates even though the treated were
      more severely ill. Although at the age of onset the suicide rates were most
      elevated, from ages 30 to 70 the rates were remarkably constant despite the
      different courses of illness. LIMITATIONS: The patients were identified as
      inpatients and followed prospectively. The treatments were uncontrolled and are
      not quantifiable but were documented during the follow-up. CONCLUSIONS: Men and
      women hospitalised for affective disorders have elevated mortality rates from
      suicide and circulatory disorders. Unipolars have higher suicide rates than
      bipolar Is or IIs. Long term medication treatment lowers the suicide rates,
      despite the fact that it was the more severely ill who were treated.

PMID- 12063146
TI  - Suicide risk in patients with anxiety disorders: a meta-analysis of the FDA
      database.
AB  - BACKGROUND: Previous reports of suicide risk in patients with anxiety disorders
      have been inconsistent. METHODS: Using the FDA database, we assessed suicide and
      suicide attempt risk among patients, participating in recent clinical trials
      evaluating new anti-anxiety medications, with diagnosis of panic disorder (PD),
      social anxiety disorder or social phobia (SP), generalized anxiety disorder
      (GAD), post traumatic stress disorder (PTSD), and obsessive compulsive disorder
      (OCD). RESULTS: Overall, among 20076 participating anxious patients, 12 committed
      suicide and 28 attempted suicide. The annual suicide risk rate was 193/100000
      patients and annual suicide attempt risk was 1350/100000 patients. LIMITATIONS:
      Clinical trial data have limited applicability to clinical practice. Participants
      in clinical trials are a highly selected, nonrepresentative sample of the
      clinical population. A number of patients never complete clinical trials and thus
      data are based on a limited sub-sample. These trials were not primarily designed
      to assess suicide risk. CONCLUSIONS: Suicide risk in patients with anxiety
      disorders is higher than previously thought. Patients with anxiety disorders
      warrant explicit evaluation for suicide risk.

PMID- 12063147
TI  - Electrophysiological evidence suggesting a seasonal modulation of retinal
      sensitivity in subsyndromal winter depression.
AB  - BACKGROUND: An anomaly in the retinal adaptation processes to the decreased light
      exposure in winter has been suggested as a contributing factor in winter
      depression. The purpose of this study was to investigate seasonal variations in
      rod sensitivity in normal subjects and in subjects with seasonal mood variations.
      METHODS: Nine normal subjects (5 men, 4 women, aged 21-28 years) and 12 subjects
      with subsyndromal seasonal affective disorder (S-SAD)(3 men, 9 women, aged 21-44
      years) were selected based on their global seasonality score (GSS) from the
      Seasonal Pattern Assessment Questionnaire. Scotopic electroretinograms (ERGs)
      were obtained once in winter and once in summer. Retinal sensitivity, which
      represents a relative threshold, was obtained from the rod ERG luminance-response
      functions. RESULTS: A difference in retinal sensitivity between the two groups
      appeared only in the winter with lower retinal sensitivity found in the S-SAD
      group. A positive correlation between the GSS and the magnitude of the winter
      decrease in rod sensitivity was also observed. LIMITATIONS: The S-SAD subjects
      studied in this research did not receive a formal psychiatric evaluation. This
      will be necessary in future studies to determine if the changes in retinal
      sensitivity are specific to seasonal affective disorders. In addition, in the
      present study, the differences in age and gender between the two groups limit the
      interpretation of the possible contribution of these two parameters to the
      results. CONCLUSION: The seasonal changes in retinal sensitivity that parallel
      seasonal mood variations suggest that the ERG may represent a useful tool to
      investigate seasonal affective disorders.

PMID- 12063148
TI  - Bipolar disorder in the general population in The Netherlands (prevalence,
      consequences and care utilisation): results from The Netherlands Mental Health
      Survey and Incidence Study (NEMESIS).
AB  - BACKGROUND: Little is known about the prevalence of bipolar disorder in the
      general population, what proportion is receiving care and what factors motivate
      people to seek help. METHOD: Data were derived from The Netherlands Mental Health
      Survey and Incidence Study (NEMESIS), a psychiatric epidemiological study in the
      general population in The Netherlands. DSM-III-R diagnoses were based on the
      Composite International Diagnostic Interview (CIDI). RESULTS: Lifetime prevalence
      of bipolar disorder was 1.9%. Compared to other mental disorders, people with
      bipolar disorder were more often incapacitated were more likely to have attempted
      suicide and reported a poorer quality of life 82.8% had experienced an additional
      mental disorder in their lifetime; 25.5% had never sought help for their
      emotional problems, not even primary, informal or alternative care. LIMITATIONS:
      Three limitations of the study are: (1) the CIDI prevalence estimates for bipolar
      disorder may be inflated; (2) personality disorders were not recorded in the
      NEMESIS dataset; (3) in NEMESIS certain groups have not been reached. CONCLUSION:
      Three-quarters of the bipolar respondents do not benefit sufficiently from the
      treatment methods now available. In view of the serious consequences of this
      condition, greater efforts are needed to reach people with bipolar disorder, to
      get them into treatment.

PMID- 12063149
TI  - Gender differences in depressive symptoms. An artefact caused by measurement
      instruments?
AB  - BACKGROUND: According to studies depression and depressive symptoms are more
      prevalent in females than in males. It is possible, however, that instruments
      meant to measure depressiveness are gender-biased. METHOD: This was studied by
      comparing two screening instruments (the Beck Depression Inventory (BDI) and the
      Depression Scale (DEPS) within the same population. The study sample consisted of
      330 subjects taken from general population in south-western part of Finland.
      RESULTS: The mean BDI scores were borderline higher in females than in males,
      with no gender difference in DEPS scores. The difference between BDI and DEPS
      scores was significant between genders but not for other variables. Crying and
      lost interest in sex were the items on which females scored higher. CONCLUSIONS:
      It has been argued that these items, crying and lost interest in sex, are
      biologically, psychologically and culturally related to female gender and,
      therefore, give gender-biased results in measuring depressiveness. CLINICAL
      IMPLICATIONS: It is important to realise that some instruments meant for
      screening depression may include gender-biased items and therefore give too high
      scores of depressiveness in females. LIMITATIONS: The study is based on self
      filled scales and its results cannot, therefore, be directly generalised to
      clinical depression.

PMID- 12063150
TI  - The economic consequences of social phobia.
AB  - Background. Social phobia has been under-recognised and under-treated in many
      countries. Little is known about its economic impact. This study aimed to
      identify the economic consequences of social phobia for individuals, health
      services and wider society. Methods. Secondary analysis of 1993-1994 Psychiatric
      Morbidity Survey data compared 63 people with social phobia and 8501 people
      without psychiatric morbidity. Results. People with social phobia were less
      likely to be in the highest socio-economic group and had lower employment rates
      and household income compared to those with no psychiatric morbidity. They also
      had higher levels of drug dependency and use of prescribed oral medications.
      Although there were no differences in total health care costs, costs of GP
      contacts were significantly higher. Individuals with a comorbid psychiatric
      disorder made higher use of some health services than those without a
      comorbidity. Limitations. Analyses were performed post hoc on data collected for
      other purposes. The defining questions for social phobia have not been studied
      much before. The number of identified subjects is small and thus raises the
      possibility of type II errors. Larger numbers may have revealed even more
      differences from the psychiatrically well population. Data on treatment patterns
      of the psychiatrically well population were limited because the surveys focused
      on subjects with psychiatric morbidity. Conclusions. The burden of social phobia
      on individuals, health services and the wider society could be reduced through
      improved rates of detection and appropriate treatment.

PMID- 12063151
TI  - Serotonin 5-HT(2A) receptor gene polymorphism, 5-HT(2A) receptor function and
      personality traits in healthy subjects: a negative study.
AB  - BACKGROUND: Central serotonin-2A (5-HT(2A)) receptor dysfunction is regarded as
      an important factor in the etiology of affective disorders. The relations between
      some personality traits and the vulnerability of affective disorders are also
      implicated. Moreover, there are several reports which describe the association
      between 5-HT(2A) receptor gene polymorphisms and mental disorders. We therefore
      examined the relationship between personality traits, the 5-HT(2A) receptor
      function, and 5-HT(2A) receptor gene polymorphisms. METHODS: 5-HT-induced
      intraplatelet calcium (Ca) mobilization, 5-HT(2A) receptor gene polymorphisms (A
      1438G, T102C, T516C, C1340T, C1354T), and Temperament and Character Inventory
      (TCI) scores were examined in 133 healthy subjects. RESULTS: Neither 5-HT-induced
      Ca mobilization nor 5-HT(2A) receptor gene polymorphisms (A-1438G, T102C) appear
      to be associated with seven personality dimensions including Harm Avoidance.
      There was no significant difference in the Ca response among the subjects with 
      1438A/A, A/G and G/G genotypes. Since the appearance of the other types of the 5
      HT(2A) receptor gene polymorphisms (T516C, C1340T and C1354T) was quite rare in
      our sample, we were unable to examine the relationship between these
      polymorphisms, and the TCI score or the Ca response. LIMITATIONS: Our failure to
      find a significant association may reflect the false negative results due to the
      small sample size and low statistical power. Further studies in depressed
      patients may clarify the complicated relationship between personality traits and
      the vulnerability of affective disorders. CONCLUSIONS: Personality traits
      detected by TCI may not be directly related to the 5-HT(2A) receptor function or
      5-HT(2A) receptor gene polymorphism which may be involved in the vulnerability of
      affective disorders.

PMID- 12063152
TI  - Fluoxetine and norfluoxetine plasma concentrations during relapse-prevention
      treatment.
AB  - BACKGROUND: Virtually no attention has been given to the relationship between
      antidepressant plasma drug concentrations and relapse-prevention during
      maintenance therapy. The purpose of this study was to investigate the
      relationship between steady-state plasma drug concentrations and outcome during
      relapse-prevention therapy with fluoxetine. METHODS: The patients studied had
      responded to acute fluoxetine treatment for major depression (defined by DSM-III
      R). Patients who met criteria for remission after 10-12 weeks of open-label acute
      fluoxetine therapy (N=395 of 839 patients), were randomly assigned to one of four
      treatment arms (50 weeks of fluoxetine, 38 weeks of fluoxetine followed by 12
      weeks of placebo, 14 weeks of fluoxetine followed by 36 weeks of placebo and 50
      weeks of placebo). Plasma fluoxetine and norfluoxetine concentrations were
      measured (1) after 4 and 8 weeks of open-label treatment and (2) at the beginning
      and after 14 weeks of double-blind, relapse-prevention therapy. RESULTS: Mean
      drug plasma levels were stable throughout the study. There was no significant
      difference in steady state plasma levels for the patients who relapsed compared
      to those who completed fluoxetine therapy without relapsing after 14, 38 or 50
      weeks of fluoxetine relapse-prevention treatment. In addition, time-to-relapse
      was not related to steady-state drug plasma levels. Finally, after dividing
      patients into two groups based on their drug plasma levels, no significant
      differences were seen in the cumulative proportions of patients staying well
      during relapse-prevention therapy. DISCUSSION: Plasma concentrations of
      fluoxetine and/or its metabolite norfluoxetine, are not correlated with relapse
      in patients treated with a fixed dose of 20 mg/day fluoxetine. Fluoxetine plasma
      levels cannot be used to guide relapse-prevention treatment.

PMID- 12063154
TI  - Influence of age and executive functioning on verbal memory of inpatients with
      depression.
AB  - BACKGROUND: Despite many studies demonstrating memory and executive impairments
      in young and old depressed patients, the relationships between age, executive
      functioning and memory have not been evaluated in depression. The aim of this
      study was to investigate if older patients were more vulnerable than younger
      patients to the impact of depression on memory and if the differences between
      young and old depressed could be related to executive functioning. METHODS: Forty
      nine inpatients, with unipolar and bipolar depression, ranging in age from 19 to
      72 years were compared with 70 controls on a verbal memory task. Age cut-off of
      45 years was used as a categorical variable to divide subjects into subgroups. A
      subset of patients (n=41) was also evaluated with the modified version of the
      Wisconsin Card Sorting Test and separated into a non-dysexecutive group and a
      group of patients with mild-executive impairment. RESULTS: Depressed patients
      exhibited memory deficits with a pattern of memory failure -- impaired free
      recall and normal cued recall and recognition -- interpreted as a retrieval
      problem. Both age and executive function influenced memory performance in
      depression, however neither group x age interaction nor age x executive status
      interaction were significant. Multiple regression analysis showed that free
      recall scores were related to age and psychomotor retardation in depressed
      patients. CONCLUSION: Age and executive functioning have different influences on
      the memory performance of depressed patients. Our findings support an 'executive
      memory decline hypothesis' in young as well as old depressed patients. The memory
      deficits in depression may be associated with both trait and state factors and
      raise questions about the long-term cognitive functioning of patients with
      recurrent affective disorders.

PMID- 12063153
TI  - Incidence of major depression: prediction from subthreshold categories in the
      Stirling County Study.
AB  - BACKGROUND: Validity of the newly-proposed categories of Minor Depression (MinD)
      and Subsyndromal Depression (SSD) would be strengthened if they were found to be
      related to the incidence of Major Depressive Episode (MDE). In this report, the
      subsequent incidence of MDE was assessed in terms of baseline evidence about the
      two subthreshold categories and Dysthymic Disorder (DysD). METHODS: The
      Diagnostic Interview Schedule was used to interview 489 subjects twice between
      1991 and 1995 as part of the Stirling County Study. Life table methods were used
      to calculate incidence rates and log linear analysis was employed for statistical
      assessment. RESULTS: The average annual incidence of MDE was 10 per 1000. The
      rates associated with the baseline categories were 210 per 1000 for DysD, 21 for
      MinD; 13 for SSD; and four for the remainder of subjects who constituted the
      reference group. Only the incidence related to DysD was significantly higher than
      that for the reference group. Comparing Time 1 and Time 2, one-third of the
      subjects gained or lost symptoms and the comorbidity of MDE and DysD increased.
      LIMITATIONS: The study population was, on average, 63 years of age. Older age and
      the small size of the cohort may have influenced the findings. Another limitation
      may relate to the use of lifetime rather than current symptomatology.
      CONCLUSIONS: DysD is strongly associated with MDE suggesting that the chronic and
      episodic forms of unipolar depression constitute one disorder. The other
      subthreshold categories should be further investigated in terms of prodromal
      qualities. The persistence of dysphoria, as in DysD, may be a more important
      feature of the depression prodrome than the number of symptoms.

PMID- 12063155
TI  - The subtypes of major depression in a twin registry.
AB  - OBJECTIVE: The subtypes of major depression (MD) remain incompletely understood.
      While there is consensus about the existence of MD with 'typical' vegetative
      features, further data are required to evaluate the existence of MD with atypical
      features. METHOD: Assessment of MD symptomatology in year prior to interview was
      available in 6846 individual twins from a population-based twin registry. The
      nine 'A' criteria for DSM-IV MD were unpacked so that the nature of sleep
      disturbance, appetite and weight changes, and motoric alterations were recorded.
      Latent class analysis was used to create an empirical typology of MD. RESULTS:
      Seven latent classes appeared to provide the best representation of the data. The
      most severe of these classes had interpretable profiles corresponding to typical
      MD, atypical MD, and 'minor' but seemingly important depressive states. These
      classes were generally more deviant than a comparison group for nearly all
      available validators. There tended to be a gradient with the typical class being
      most extreme, minor depressive classes the least extreme, and the atypical class
      having an intermediate position. CONCLUSIONS: Our findings support the existence
      of atypical depression as a phenomenological subtype of MD. Besides the
      differences in symptom patterns, there are many more similarities than
      differences across a range of external validators. Similar to other reports, we
      found evidence of the importance and morbidity of depressive symptomatology that
      does not meet the DSM-IV MD thresholds.

PMID- 12063156
TI  - Effects of supraphysiological thyroxine administration in healthy controls and
      patients with depressive disorders.
AB  - BACKGROUND: Thyroxine (T(4)) in supraphysiological doses has been found to be an
      effective supplemental treatment in open studies for refractory mood disorders.
      Unexpectedly, only minimal side effects have been reported. The goal of the
      present study was to investigate whether healthy controls and depressed patients
      differ in their ability to tolerate supraphysiological doses of T(4). METHODS:
      This was an 8-week open study to investigate side effects and levels of thyroid
      hormones in 13 healthy controls and to compare results with those of 13 patients
      with refractory depression (unipolar and bipolar) undergoing the similar
      procedures and T(4) dosing regimen in a previous augmentation study. RESULTS: The
      rate of discontinuation due to side effects was significantly higher in the
      control group than for the patients (38% versus 0%). The severity of the side
      effects in the controls increased significantly during treatment with T(4). The
      side effect scores of the patients were higher than those of the controls prior
      to T(4) treatment, but did not change significantly during the treatment period.
      Although the serum concentrations of thyroid hormones rose significantly in both
      groups, concentrations of fT(3) and fT(4) were significantly higher in the
      controls. CONCLUSIONS: Healthy controls and depressed patients respond
      significantly differently to supraphysiological T(4). Healthy controls experience
      higher elevations of thyroid hormones in response to supraphysiological T(4),
      thus inducing significantly more side effects and discontinuation. LIMITATIONS:
      Open-label study; groups were studied at different times; in contrast to healthy
      controls, depressed patients were also taking antidepressants. CLINICAL
      RELEVANCE: Studies provide safety and tolerability data on treatment with
      supraphysiological doses of T(4).

PMID- 12063157
TI  - Psychotic symptoms in major depressive disorder are associated with reduced
      regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxel
      based single photon emission computed tomography (SPECT) study.
AB  - BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe
      major depressive episodes. Functional imaging studies of depression have been
      widely reported in the literature, but few of these have attempted to investigate
      the neurophysiological correlates of psychotic symptoms. METHODS: We measured
      resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique
      in patients with major depressive disorder with (n=9) and without (n=12)
      psychotic features, as well as in a group of healthy volunteers (n=12). Between
      group rCBF comparisons were performed using the voxel-based statistical
      parametric mapping method. RESULTS: Major depressed patients with psychotic
      features showed decreased rCBF in the left subgenual anterior cingulate cortex
      relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed,
      uncorrected for multiple comparisons). Relative to the non-psychotic group,
      depressed patients with psychotic symptoms also had a focus of decreased rCBF in
      the right inferior frontal cortex, with the voxel of maximal significance in the
      insula (P<0.031, corrected for multiple comparisons). A similar pattern of
      significant between-group rCBF differences between psychotic and non-psychotic
      patients emerged after covarying the analysis for the confounding influence of
      overall illness severity. CONCLUSIONS: These results provide preliminary evidence
      that psychotic symptoms in major depression may be associated with abnormalities
      in ventral paralimbic regions previously implicated in mood regulation and
      depression.

PMID- 12063158
TI  - Defining guilt in depression: a comparison of subjects with major depression,
      chronic medical illness and healthy controls.
AB  - BACKGROUND: Although guilt is a widely accepted feature of depression, there is
      limited and inconsistent data defining the nature of this symptom. The purpose of
      the current study was to examine the specificity and nature of guilt in subjects
      with major depression as compared to patients with another chronic medical
      illness and healthy controls. METHODS: Outpatients with current major depressive
      episode (MDE; n=34), past-MDE (n=22), chronic cardiac illness (n=20) and healthy
      controls (n=59) were administered the following measures: The Guilt Inventory
      (GI), State Shame and Guilt Scale (SSGS), 17-item Hamilton Rating Scale for
      Depression (Ham-D) and the Structured Clinical Interview for DSM-IV. RESULTS:
      Overall multivariate analysis of covariance comparing mean scores for the six
      guilt subscales [state-guilt, trait-guilt, moral standards (from the GI); state
      guilt, -pride, and -shame (from the SSGS)] across the four groups was significant
      (F=9.1, df=6:121, p<0.0001). Post-hoc analysis revealed the following differences
      (each at least p<0.01): for state-guilt (GI), current-MDE>past
      MDE>cardiac=healthy controls; for trait-guilt (GI), current-MDE=past
      MDE>cardiac=healthy controls; for state-shame, -guilt and -pride (SSGS), current
      MDE>past-MDE, past-MDE=cardiac, past-MDE>healthy, cardiac=healthy controls. Among
      depressed patients, there was significant correlation between Ham-D score and all
      guilt sub-scales (p<0.01), except moral standards. LIMITATIONS: The cardiac group
      may have less illness burden than currently depressed. CONCLUSIONS: State
      expression of guilt, shame and low pride distinguish acutely depressed from all
      other groups, and are highly influenced by severity of depression. Trait-guilt
      does not differentiate acute from past depressed. Data suggests guilt may
      represent both an enduring and fluctuating feature of depressive illness over its
      longitudinal course.

PMID- 12063159
TI  - Sertraline and/or interpersonal psychotherapy for patients with dysthymic
      disorder in primary care: 6-month comparison with longitudinal 2-year follow-up
      of effectiveness and costs.
AB  - BACKGROUND: There is little information on the long-term effects and costs of a
      combination of Sertraline and interpersonal psychotherapy (IPT) for the treatment
      of dysthymia in primary care. METHODS: In a single-blind, randomized clinical
      trial, 707 adults (18-74 years of age inclusive) with DSM-IV dysthymic disorder,
      with or without past and/or current major depression, as an acute or chronic
      episode, in a community-based primary care practice in Ontario, Canada, were
      randomized to treatment with either Sertraline alone (50-200 mg), or IPT alone
      (10 sessions), or Sertraline plus IPT combined. In the acute treatment phase
      (first 6 months) all groups received full active treatment. This was followed by
      an additional 18-month naturalistic follow-up phase. Subjects were assessed for
      effectiveness of treatment in reducing depressive symptoms using the Montgomery
      Asberg Depression Rating Scale (MADRS) at 6 months and twice again during the 18
      month follow-up by blind independent observers. Treatment costs and subjects' use
      of other health and social services were also investigated. RESULTS: At 6 months,
      586 subjects completed the MADRS questionnaire. There was a significant
      difference (P=0.025) in mean MADRS scores: 14.3 (Group I); 14.9 (Group II); 16.8
      (Group III), using analysis of covariance. Response (40% improvement) rates were
      60.2% for Sertraline alone, 46.6% for IPT alone, and 57.5% for Sertraline
      augmented by IPT (P=0.02). At 2 years, 525 subjects were retained for follow-up.
      There was no statistically significant difference between Sertraline alone and
      Sertraline plus IPT in symptom reduction. However, both were more effective than
      IPT alone in reducing depressive symptoms (P=0.03). There was a statistically
      significant difference between groups in costs for use of health and social
      services. The IPT treatment groups had the lower costs for use of health and
      social services. CONCLUSIONS: Sertraline or Sertraline plus IPT was more
      effective than IPT alone after 6 months. Over the long term (2 years), all three
      treatments provide reasonably effective treatment for reducing symptoms of
      dysthymia, but Sertraline or combining Sertraline with IPT is more effective than
      IPT alone. Of these two more effective treatments, subjects in the Sertraline
      plus IPT group had less health and social service costs by $480 per person over 2
      years. These findings underscore the effects of combining pharmacotherapy and
      psychotherapy and the economic value of this more comprehensive treatment of
      dysthymia in primary care.

PMID- 12063160
TI  - Plasma catecholamine metabolites in antidepressant-exacerbated mania and
      psychosis.
AB  - We measured plasma free HVA and MHPG in 39 cases of psychosis or mania judged to
      be caused by antidepressant exacerbation of symptoms. A total of 24 of patients
      had been receiving selective serotonin reuptake inhibitors (SSRI's). The SSRI
      group showed a pattern of increased plasma HVA similar to a comparison group of
      patients with a psychotic/manic relapse secondary to medication non-compliance.

PMID- 12063161
TI  - Panic disorder and obsessive compulsive disorder in a hyperventilation challenge
      test.
AB  - BACKGROUND: Stress-induced hyperventilation produces symptoms that people are
      prone to misinterpret as life-threatening if they are unaware of the consequences
      of overbreathing. Our aim was to observe the induction of panic attacks by a
      hyperventilation challenge test in a series of panic disorder and obsessive
      compulsive disorder (OCD) patients (DSM-IV). METHOD: We randomly selected 28
      panic disorder patients, 21 OCD patients and 28 normal volunteers. All patients
      were drug free for a week. They were induced to hyperventilate (30 breaths/min)
      for 4 min. Anxiety scales were applied before and after the test. RESULTS: A
      total of 64.3% (n=18) panic disorder patients, 9.5% (n=2) OCD patients and 3.6%
      (n=1) of control subjects had a panic attack after hyperventilating (chi(2)=3.99,
      d.f.=2, P=0.026). LIMITATIONS: The hyperventilation challenge test has a low
      sensitivity for panic disorder. CONCLUSION: In this challenge test the panic
      disorder patients were more sensitive to hyperventilation than OCD patients and
      normal volunteers. The induction of panic attacks by voluntary hyperventilation
      may be an easy test for validating the diagnosis in certain panic disorder
      patients.

PMID- 12063162
TI  - Treatment compliance in light therapy: Do patients do as they say they do?

PMID- 12063163
TI  - Further evidence for age of onset being an indicator for severity in bipolar
      disorder.

PMID- 12063165
TI  - Participation of the conventional calpains in apoptosis.
AB  - The conventional calpains, m- and micro-calpain, are suggested to be involved in
      apoptosis triggered by many different mechanisms. However, it has not been
      possible to definitively associate calpain function with apoptosis, largely
      because of the incomplete selectivity of the cell permeable calpain inhibitors
      used in previous studies. In the present study, Chinese hamster ovary (CHO) cell
      lines overexpressing micro-calpain or the highly specific calpain inhibitor
      protein, calpastatin, have been utilized to explore apoptosis signals that are
      influenced by calpain content. This approach allows unambiguous alteration of
      calpain activity in cells. Serum depletion, treatment with the endoplasmic
      reticulum (ER) calcium ATPase inhibitor thapsigargin, and treatment with calcium
      ionophore A23187 produced apoptosis in CHO cells, which was increased in calpain
      overexpressing cells and decreased by induced expression of calpastatin.
      Inhibition of calpain activity protected beta-spectrin, but not alpha-spectrin,
      from proteolysis. The calpains seemed not to be involved in apoptosis triggered
      by a number of other treatments. Calpain protected against TNF-alpha induced
      apoptosis. In contrast to previous studies, we found no evidence that calpains
      proteolyze I kappa B-alpha in TNF-alpha-stimulated cells. These studies indicate
      that the conventional calpains participate in some, but not all, apoptotic
      signaling mechanisms. In most cases, they contributed to apoptosis, but in at
      least one case, they were protective.

PMID- 12063164
TI  - Transforming growth factor-beta1 regulation of growth zone chondrocytes is
      mediated by multiple interacting pathways.
AB  - Transforming growth factor beta 1 (TGF-beta1) affects growth plate chondrocytes
      through Smad-mediated mechanisms and has been shown to increase protein kinase C
      (PKC). This study determined if PKC mediates the physiological response of rat
      costochondral growth zone (GC) chondrocytes to TGF-beta1; if the physiological
      response occurs via type II or type III TGF-beta receptors, and, if so, which
      receptor mediates the increase in PKC; and the signal transduction pathways
      involved. Treatment of confluent GC cells with TGF-beta1 stimulated
      [(3)H]thymidine and [(35)S]sulfate incorporation as well as alkaline phosphatase
      (ALPase) and PKC specific activities. Inhibition of PKC with chelerythrine,
      staurosporine, or H-7 caused a dose-dependent decrease in these parameters,
      indicating that PKC signaling was involved. TGF-beta1-dependent PKC and the
      physiological response of GC cells to TGF-beta1 was reversed by anti-type II TGF
      beta receptor antibody and soluble type II TGF-beta receptor, showing that TGF
      beta1 mediates these effects through the type II receptor. The increase in
      [3H]thymidine incorporation and ALPase specific activity were also regulated by
      protein kinase A (PKA) signaling, since the effects of TGF-beta1 were partially
      blocked by the PKA inhibitor H-8. The mechanism of TGF-beta1 activation of PKC is
      through phospholipase A(2) (PLA(2)) and not through phospholipase C (PLC).
      Arachidonic acid increased PKC in control cultures and was additive with TGF
      beta1. Prostanoids are required, as indomethacin blocked the effect of TGF-beta1,
      and Cox-1, but not Cox-2, is involved. TGF-beta1 stimulates prostaglandin E(2)
      (PGE(2)) production and exogenous PGE(2) stimulates PKC, but not as much as TGF
      beta1, suggesting that PGE(2) is not sufficient for all of the prostaglandin
      effect. In contrast, TGF-beta1 was not regulated by diacylglycerol; neither
      dioctanoylglycerol (DOG) nor inhibition of diacylglycerol kinase with R59022 had
      an effect. G-proteins mediate TGF-beta1 signaling at different levels in the
      cascade. TGF-beta1-dependent increases in PGE(2) levels and PKC were augmented by
      the G protein activator GTP gamma S, whereas inhibition of G-protein activity via
      GDP beta S, pertussis toxin, or cholera toxin blocked stimulation of PKC by TGF
      beta1, indicating that both G(i) and G(s) are involved. Inhibition of PKA with H
      8 partially blocked TGF-beta1-dependent PKC, suggesting that PKA inhibition on
      the physiological response was via PKA regulation of PKC signaling. This
      indicates that multiple interacting signaling pathways are involved: TGF-beta1
      stimulates PLA(2) and prostaglandin release via the action of Cox-1 on
      arachidonic acid. PGE(2) activates the EP2 receptor, leading to G-protein
      dependent activation of PKA. PKA signaling results in increased PKC activity and
      PKC signaling regulates proliferation, differentiation, and matrix synthesis.

PMID- 12063166
TI  - Characterisation of two 14-3-3 genes from Trichoderma reesei: interactions with
      yeast secretory pathway components.
AB  - The 14-3-3 proteins are highly conserved, ubiquitously expressed proteins taking
      part in numerous cellular processes. Two genes encoding 14-3-3 proteins, ftt1 and
      ftt2, were isolated and characterised from the filamentous fungus Trichoderma
      reesei. FTTI showed the highest sequence identity (98% at the amino acid level)
      to the Trichoderma harzianum protein Th1433. FTTII is relatively distinct from
      FTTI, showing approximately 75% identity to other fungal 14-3-3 proteins. Despite
      their sequence divergence, both of the T. reesei ftt genes were equally able to
      complement the yeast bmh1 bmh2 double disruption. The T. reesei ftt genes were
      also found to be quite closely linked in the genomic DNA. A C-terminally
      truncated version of ftt1 (ftt1DeltaC) was first isolated as a multicopy
      suppressor of the growth defect of the temperature-sensitive yeast secretory
      mutant sec15-1. Overexpression of ftt1DeltaC also suppressed the growth defect of
      sec2-41, sec3-101, and sec7-1 strains. Overexpression of ftt1DeltaC in sec2-41
      and sec15-1 strains could also rescue the secretion of invertase at the
      restrictive temperatures, and overexpression of full-length ftt1 enhanced
      invertase secretion by wild-type yeast cells. These findings strongly suggest
      that the T. reesei ftt1 has a role in protein secretion.

PMID- 12063168
TI  - Antisense inhibition of myoD expression in regenerating rat soleus muscle is
      followed by an increase in the mRNA levels of myoD, myf-5 and myogenin and by a
      retarded regeneration.
AB  - It has been reported that muscles of myoD-/- mice present a lower potential to
      regenerate, but there are no reports on the effect of acute interference with
      myoD expression limited in space and time to only a particular regenerating
      muscle. Here we relied on antisense inhibition of this factor. Four different
      oligos were tested. The suppression of regeneration indices (the expression of
      desmin, the formation of myotubes and the initiation of endplates) was the most
      pronounced, with the oligomer targeting a region encompassing the translation
      start site of myoD. A mixed backbone phosphorothioate-phosphate diester oligo
      (200 microl at 20 microM) was still detectable in the muscles 1 h after its
      administration and reverse transcription-polymerase chain reaction (RT-PCR)
      analysis showed that the level of the targeted 5' end of the myoD mRNA was
      selectively decreased. The level of myoD protein was also lowered. Four hours
      after the antisense treatment, when the oligos were no longer detectable, the
      myoD mRNA level was restored and 24 h later it exceeded controls together with
      that of myf-5 and myogenin. After 4 weeks, the antisense-treated soleus muscles
      were similar to the control-treated and the untreated regenerated soleus with
      respect to fiber types and motor endplates, however, they contained smaller
      fibers which reflected the asynchronity of regeneration. This shows that
      successfully targeted simple antisense oligonucleotides can be used as selective
      tools for inhibition of individual factors in studying the process of muscle
      regeneration.

PMID- 12063167
TI  - Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL
      1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial
      cells.
AB  - beta-defensin 2 is produced by a variety of epithelial cell types in the body and
      exhibits potent antimicrobial activity against a variety of pathogens, including
      the bacteria that are most commonly associated with otitis media (OM). The human
      beta-defensin 2 (hBD-2) gene is an NF-kappa B regulated gene and a variety of
      proinflammatory stimuli can induce its expression. Although the presence of
      molecules of innate immunity such as lysozyme and lactoferrin has been
      demonstrated in the middle ear, to date there have been no reports on the
      expression of beta-defensin 2. In the present study, we demonstrate that beta
      defensin 2 is expressed in the middle ear mucosa of humans and rats. We also show
      that it is expressed in a human middle ear epithelial cell line and that its
      expression is induced by proinflammatory stimuli such as interleukin 1 alpha (IL
      1 alpha), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS).
      Moreover, we demonstrate that the transcriptional activation of hBD-2 gene by IL
      1 alpha is mediated through an Src-dependent Raf-MEK1/2-ERK signaling pathway.

PMID- 12063169
TI  - Role of human organic anion transporter 4 in the transport of ochratoxin A.
AB  - The purpose of this study was to investigate the characteristics of ochratoxin A
      (OTA) transport by multispecific human organic anion transporter 4 (hOAT4) using
      mouse proximal tubule cells stably transfected with hOAT4 (S(2) hOAT4).
      Immunohistochemical analysis revealed that hOAT4 protein was localized to the
      apical side of the proximal tubule. S(2) hOAT4 expressed hOAT4 protein in the
      apical side as well as basolateral side and the cells were cultured on the
      plastic dish for experiments. S(2) hOAT4 exhibited a time- and concentration
      dependent, and a saturable increase in OTA uptake, with an apparent K(m) value of
      22.9+/-2.44 microM. The OTA uptakes were inhibited by several substrates for the
      OATs. Probenecid, piroxicam, octanoate and citrinin inhibited OTA uptake by hOAT4
      in a competitive manner (K(i)=44.4-336.4 microM), with the following order of
      potency: probenecid > piroxicam > octanoate >citrinin. The efflux of OTA by S(2)
      hOAT4 was higher than that by mock. Addition of OTA resulted in slight decrease
      in viability of S(2) hOAT4 compared with mock. These results indicate that hOAT4
      mediates the high-affinity transport of OTA on the apical side of the proximal
      tubule, whereas the transport characteristics of OTA are distinct from those by
      basolateral OATs.

PMID- 12063170
TI  - Distinct mechanisms of taxol-induced serine phosphorylation of the 66-kDa Shc
      isoform in A549 and RAW 264.7 cells.
AB  - Nanomolar concentrations of Taxol, and other antimitotic agents that interact
      with microtubules, mediate serine phosphorylation of the 66-kDa Shc isoform
      (p66shc) in A549 human lung carcinoma cells, 9-18 h after drug treatment. This
      event coincides with the release of PARP cleavage fragments that are early
      indicators of apoptosis. Taxol-induced serine phosphorylation of p66shc results
      from a MEK-independent signaling pathway that is activated in A549 cells that
      have a prolonged or abnormal mitotic phase of the cell cycle [Cancer Res. 60
      (2000) 5171]. In contrast, in murine macrophage RAW 264.7 cells, micromolar
      concentrations of Taxol but not other microtubule-interacting agents induced
      serine phosphorylation of p66shc that correlated with the phosphorylation of Raf
      1 and extracellular signal-regulated kinase (ERK1/2), within 15-30 min after
      Taxol treatment. This event also was induced by lipopolysaccharide (LPS). The MEK
      inhibitor, U0126, that specifically inhibits the activation of ERK also blocked
      the phosphorylation of p66shc and Raf-1, suggesting that these processes were MEK
      dependent, quite different from that which was observed in A549 cells. Taxol also
      induced phosphorylation of p38 and JNK MAP kinases within 8-15 min after drug
      treatment. It is known that Taxol, but not other microtubule-interacting agents,
      induces the production of cytokines, such as tumor necrosis factor alpha (TNF
      alpha) in mouse macrophages. The time course of Taxol-induced TNF-alpha
      expression coincides with that of Taxol-induced p66shc phosphorylation, and U0126
      inhibits significantly Taxol-induced TNF-alpha expression in RAW 264.7 cells. Our
      data indicate that the Taxol-induced serine phosphorylation of p66shc in RAW
      264.7 cells is microtubule-independent and may be related to increased TNF-alpha
      expression after Taxol and LPS treatment. It is concluded that the mechanisms
      involved in Taxol-induced p66shc phosphorylation are distinct in A549 and RAW
      264.7 cells.

PMID- 12063171
TI  - Type IV phosphodiesterase activity specifically regulates cAMP-stimulated casein
      secretion in the rat mammary gland.
AB  - This study investigates the regulation of cAMP-stimulated casein secretion in rat
      mammary explants by cAMP phosphodiesterase (cAMP-PDE) activity. cAMP-PDE activity
      of the lactating rat mammary gland is shown to be provided by three families,
      types II, III and IV. In mammary explants, general inhibition of the cAMP-PDE
      activity significantly increased the rate of cAMP-stimulated casein secretion.
      This effect could be mimicked using the type-IV specific inhibitor rolipram but
      not by the specific, or combined, inhibition of the type II and type III
      activity. Only type IV activity significantly affected intracellular accumulation
      of cAMP whereas all three cAMP-PDE activities were shown to influence the PKA
      activation ratio in cells. RtPCR analysis showed that the mammary gland
      apparently expresses just three type IV isozymes, RNPDE4A5, RNPDE4A8 and
      RNPDE4D3. A specific role for type IV cAMP-PDE activity in the regulation of
      casein secretion is suggested and possible mechanisms for the effects of PDEIV
      activity discussed.

PMID- 12063173
TI  - Matrix association of early- and late-replicating chromatin studied by single
      cell electrophoresis.
AB  - CHO-K1 cells were synchronized at the G(1)/S border by mitotic shake-off and
      aphidicolin incubation. Pulse-labeling with tritium was done at 30 min, 2 or 5 h
      into the S-phase, with chase incubations for different times in non-radioactive
      medium. The cells were subjected to neutral microelectrophoresis to extend the
      DNA into "comets," after which the label was visualized through autoradiography.
      At zero chase time, all label was positioned in the head. The displacement of
      label into the tails increased with time, reaching a maximum at about 5 h after
      the pulse. A lag phase of 2-3 h was observed for the early-labeled cells before
      the displacement started. Also, more label was released after overnight serum
      starvation, but this was reversed through a 3-h incubation at normal growth
      conditions. It was found that late-replicating chromatin is organized in larger
      domains than early-replicating chromatin, and DNA polymerase seems to be an
      important organizer. Early-replicating chromatin has other important attachments
      to the nuclear matrix, dependent on metabolic activity.

PMID- 12063172
TI  - Interaction of S-adenosylhomocysteine hydrolase of Xenopus laevis with
      mRNA(guanine-7-)methyltransferase: implication on its nuclear
      compartmentalisation and on cap methylation of hnRNA.
AB  - S-adenosylhomocysteine hydrolase (SAHH) is the only enzyme known to cleave S
      adenosylhomocysteine (SAH), a product and an inhibitor of all S
      adenosylmethionine-dependent transmethylation reactions. Xenopus SAHH is a
      nuclear enzyme in transcriptionally active cells and inhibition of xSAHH prevents
      cap methylation of hnRNA [Mol. Biol. Cell 10 (1999) 4283]. Here, we demonstrate
      that inhibition of xSAHH in Xenopus XTC cells results in a cytoplasmic
      accumulation of the shuttling hnRNPs, while xSAHH itself remains in the nucleus.
      The functional link between xSAHH and mRNA cap methylation is further supported
      by a physical association between xSAHH and mRNA(guanine-7-)methyltransferase
      (CMT). We show by co-immunoprecipitation of tagged proteins that both enzymes
      interact in vivo. Direct interaction in vitro is shown by pull-down experiments
      that further demonstrate that the N-terminal 55 amino acids of xSAHH are
      sufficient for binding to CMT. Since CMT is known to bind to the
      hyperphoshorylated C-terminal domain (CTD) of its large subunit of RNA polymerase
      II, we have studied the co-localisation of RNA polymerase II and xSAHH in oocyte
      nuclei. Immunolocalisation on spreads of lampbrush chromosomes shows xSAHH on the
      loops of the transcriptionally active lampbrush chromosomes, in Cajal bodies and
      in B-snurposomes, the nuclear compartments that are most likely engaged in
      storage and recycling of RNA polymerase II and its cofactors. We therefore
      suggest that a subfraction of the nuclear xSAHH remains associated with the RNA
      polymerase holoenzyme complexes, also while these are not actively engaged in
      transcription.

PMID- 12063174
TI  - A calcium-permeable channel activated by muscarinic acetylcholine receptors and
      InsP3 in developing chick ciliary ganglion neurons.
AB  - The electrical responses elicited by the muscarinic cholinergic pathway have been
      studied in cultured embryonic chick ciliary ganglion (CG) neurons. Neurons
      obtained from E7-E8 ganglia were maintained in serum-free medium for 1 to 3 days.
      Stimulation with 50 microM muscarine induced depolarizing responses in about 30%
      of the cells tested. In voltage clamp experiments at a holding potential of -50
      mV, an inward current could be recorded in the same percentage of cells in
      response to muscarinic stimulation. In single channel experiments, with standard
      physiological solution in the pipette, muscarine transiently activated an inward
      conducting channel. Cell-attached recordings with 100 mM CaCl(2) in the pipette
      provided evidence that muscarinic agonists can activate a cationic calcium
      permeable channel. Two main conductance levels could be detected, of 2.3+/-0.6
      and 5.6+/-0.6 pS, respectively. In excised patches, addition of 5-20 microM
      inositol 1,4,5-trisphosphate (InsP(3)) to the bath reactivated a channel that
      could be blocked by heparin and whose characteristics were very similar to those
      of the channel seen in response to muscarinic stimulation. A channel with similar
      properties has been previously shown to be activated by basic fibroblast growth
      factor (bFGF) and InsP(3) in the same preparation.

PMID- 12063175
TI  - Inhibition of Rho/Rho-kinase signaling downregulates plasminogen activator
      inhibitor-1 synthesis in cultured human monocytes.
AB  - Increased production of plasminogen activator inhibitor-1 (PAI-1) in plaques
      plays a role in the pathogenesis of atherosclerosis. This study was conducted to
      investigate the effect of blockade of Rho/Rho-kinase signaling on the synthesis
      of PAI-1 in cultured human peripheral blood monocytes. HMG-CoA reductase
      inhibitors (statins) and inhibitors of Rho and Rho-kinase were added to monocyte
      cultures. The levels of PAI antigen and mRNA were determined by Western blotting
      and RT-PCR, respectively, and PAI-1 expression was assessed by
      immunohistochemistry. We performed pull-down assays to determine the activity of
      Rho by measuring the GTP-bound form of Rho A. In unstimulated and
      lipopolysaccharide (LPS)-stimulated cultured monocytes, statins reduced the
      levels of PAI-1 antigen and mRNA. The suppressive effects of statins on PAI-1
      synthesis were reversed by geranylgeranylpyrophosphate (GGPP) and were mimicked
      by C3 exoenzyme. Immunohistochemistry confirmed the role of lipid modification by
      GGPP in suppressive effect of statins in PAI-1 synthesis. Pull-down assays
      demonstrated that statins decreased the levels of the GTP-bound form of Rho A.
      Our findings suggest that statins decrease the activity of Rho by inhibiting
      geranylgeranylation. Moreover, Rho-kinase inhibitors, Y-27632 and fasudil,
      suppressed the synthesis of PAI-1 in this culture system. We show that inhibition
      of Rho/Rho-kinase signaling downregulates the synthesis of PAI-1 in human
      monocytes.

PMID- 12063176
TI  - Chemical camouflage of nanospheres with a poorly reactive surface: towards
      development of stealth and target-specific nanocarriers.
AB  - A two-step approach is described to chemically camouflage the inert surface of
      model polystyrene nanospheres of 60 nm in diameter against recognition by the
      body's defenses. The first step was based on the strong protein adsorbing potency
      of polystyrene, and the second step utilized the chemical reactivity of the
      adsorbed proteins for conjugation with cyanuric chloride-activated
      methoxypoly(ethyleneglycol)5000, mPEG5000. Bovine serum albumin (BSA) and rat IgG
      were used as models of non-immune and immune proteins, respectively. The maximum
      adsorbance values for both proteins were near expectation for a close-packed
      monolayer. Adsorption isotherms studies and analysis of the hydrodynamic
      thickness of the adsorbed protein layer confirmed the close-packed side-on mode
      of adsorption for BSA and the end-on mode of adsorption for IgG, respectively.
      Nucleophiles on the adsorbed proteins were then reacted with cyanuric chloride
      activated mPEG5000. The average poly(ethyleneglycol) (PEG) content for a 60-nm
      nanospheres was found to be 13.7+/-0.4 micromol PEG/micromol BSA and 3.6+/-0.3
      micromol PEG/micromol IgG. The interaction of both PEG-bearing nanospheres with
      the hydrophobic column material octyl-agarose indicated surface heterogeneity
      among the nanospheres. Only nanospheres with the most hydrophilic phenotype
      (approximately 70% of the total population) exhibited stealth properties after
      intravenous injection to rats. In contrast to the described approach, incubation
      of uncoated nanospheres with preformed BSA-mPEG5000 conjugates failed to produce
      long circulating entities. For design of splenotropic particles cyanuric chloride
      activated mPEG5000 was conjugated to BSA-coated polystyrene beads of 225 nm in
      diameter. Despite their stealth property to hepatic Kupffer cell recognition,
      these nanospheres were cleared by the splenic red pulp macrophages.

PMID- 12063177
TI  - 2',5'-oligoadenylate synthetase from a lower invertebrate, the marine sponge
      Geodia cydonium, does not need dsRNA for its enzymatic activity.
AB  - Recently, the presence of 2',5'-linked oligoadenylates and a high 2',5'
      oligoadenylate synthetase activity were discovered in a lower invertebrate, the
      marine sponge Geodia cydonium. It has been demonstrated that mammalian 2-5A
      synthetase isozymes require a dsRNA cofactor for their enzymatic activity. Our
      results show that, unlike mammalian 2-5A synthetases, the 2-5A synthetase from
      the sponge acts in a dsRNA-independent manner in vitro. A prolonged incubation of
      the G. cydonium extract with a high concentration of a micrococcal nuclease had
      no effect on the activity of the 2-5A synthetase. At the same time, the
      micrococcal nuclease was effective within 30 min in degrading dsRNA needed for
      the enzymatic activity in IFN-induced PC12 cells. These results indicate that the
      2-5A synthetase from G. cydonium may be active per se or is activated by some
      other mechanism. The sponge enzyme is capable of synthesizing a series of 2-5A
      oligomers ranging from dimers to octamers. The accumulation of a dimer in the
      predominant proportion during the first stage of the reaction was observed,
      followed by a gradual increase in longer oligoadenylates. By its product profile
      and kinetics of formation, the sponge 2-5A synthetase behaves like a specific
      isoform of enzymes of the 2-5A synthetase family.

PMID- 12063178
TI  - Establishment of two immortalized nasopharyngeal epithelial cell lines using SV40
      large T and HPV16E6/E7 viral oncogenes.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer in Southeast Asia, especially
      in southern China. One of the most striking features of this disease is its close
      relationship with Epstein-Barr Virus (EBV). However, to date there is no direct
      study on the mechanisms involved in the role of EBV in the tumorigenesis of NPC,
      largely due to lack of an experimental model. Available hypotheses on the
      association between EBV and NPC are generated from non-nasopharyngeal epithelial
      cell systems such as human keratinocytes or mouse epithelial cells, which may not
      truly represent the biological properties of nasopharyngeal epithelial (NP)
      cells. In this study, we report the establishment of two immortalized NP cell
      lines, NP69SV40T and NP39E6/E7, using SV40T and HPV16E6/E7 oncogenes. We found
      that NP60SV40T and NP39E6/E7 cell lines not only maintained many characteristics
      of normal NP cells (i.e. keratin profile and responsive to TGFbeta inhibition)
      but also highly responsive to one of the EBV encoded genes, LMP1. Comparative
      genome hybridization (CGH) analysis showed that these two cell lines contained
      multiple genetic alterations, some of which have been described in NPC. The
      immortalized NP cell lines are non-tumorigenic and exhibit anchorage-dependent
      growth. These cell lines may provide a possible cell model system for studying
      the mechanisms involved in the tumorigenesis of NPC.

PMID- 12063179
TI  - Synaptotagmin II could confer Ca(2+) sensitivity to phagocytosis in human
      neutrophils.
AB  - Phagolysosome fusion and granule exocytosis in neutrophils are calcium-dependent
      processes. The calcium requirements vary between granule types, suggesting the
      presence of different calcium sensors. The synaptotagmins, a family of calcium
      binding proteins, previously shown to participate in vesicle fusion and vesicle
      recycling in excitable cells, are putative calcium-sensors of exocytosis in
      excitable cells. In this study, we show that synaptotagmin II is present in human
      neutrophils and may participate in phagocytic and in exocytotic processes. In
      protein extracts from human neutrophils, we identified synaptotagmin II by
      Western blot as an 80 kDa protein. Subcellular fractionation revealed that
      synaptotagmin II was associated with the specific granules. In fMLP-stimulated
      cells, synaptotagmin II translocated to the plasma membrane. This correlated with
      the upregulation of complement receptor 3 (CR 3), reflecting the translocation of
      specific granules to the cell surface. Synaptotagmin II also translocated to the
      phagosome after complement-mediated phagocytosis in the presence of calcium. LAMP
      1 translocated in parallel but probably was located to another subcellular
      compartment than synaptotagmin II. Under calcium-reduced conditions, neither
      synaptotagmin II nor LAMP-1 translocated to the phagosome. We therefore suggest a
      role for synaptotagmin II as calcium-sensor during phagocytosis and secretion in
      neutrophils.

PMID- 12063180
TI  - Regulation of TIMP-1 phenotypic expression in Epstein--Barr virus-immortalized B
      lymphocytes.
AB  - Normal B lymphocytes as well as malignant B cells extravasate from blood
      circulation during physiological and pathological processes and require matrix
      metalloproteinases (MMPs) to facilitate trafficking through the subendothelial
      basal lamina and the extracellular matrix. We have previously shown that Epstein
      Barr virus (EBV)-immortalized B lymphocytes constitutively synthesized low levels
      of MMP-9 and huge amounts of its preferential inhibitor, tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1). In the present study, TIMP-1 phenotypic
      expression was extensively investigated in response to various mediators
      including interleukins, chemokines, growth factors and tumor promotor, and was
      compared to MMP-9 synthesis. Results showed a roughly constitutive TIMP-1
      expression opposed to an inducible MMP-9 synthesis. Nevertheless, further
      analysis of TIMP-1 synthesis showed the existence of regulation mechanisms:
      modulation of intracellular Ca(2+) concentration as well as cation ionophore
      monensin were demonstrated to influence TIMP-1 production and secretion. The
      precise pathways implicated in these regulation mechanisms are currently under
      survey.

PMID- 12063181
TI  - Recent insights into the origins of adrenal and sex steroid receptors.
AB  - The recent cloning by Thornton (2001) of estrogen, progesterone and corticoid
      receptors from lamprey provides important insights into the early evolution of
      adrenal and sex steroid receptors and an opportunity to elucidate the ancient
      steroids that regulated gene transcription. Inclusion of lamprey sequences in a
      steroid receptor phylogeny indicates that the estrogen receptor is the most
      ancient of these receptors, followed by the progesterone receptor and the
      corticoid receptor. Thornton proposed that estradiol was the earliest of the
      steroids to activate a steroid receptor. An alternative hypothesis is that a
      steroid in the Delta(5) pathway activated the ancestral estrogen receptor.

PMID- 12063182
TI  - Characterization of oestrogen receptors in zebrafish (Danio rerio).
AB  - We cloned the cDNAs corresponding to three oestrogen receptors (ERs) in zebrafish
      (Danio rerio). Sequence analysis and phylogenetic studies demonstrated that two
      of these genes, ER beta.1 and ER beta.2, arose from duplication of the original
      ER beta in many species of the fish phylum, whereas ER alpha is unique. Zebrafish
      ERs behaved as oestrogen-dependent transcription factors in transactivation
      assays. However, their reactivity to various oestrogen modulators was different
      compared with that of mouse ERs. ER mRNA expression during zebrafish development
      is restricted to distinct time periods, as observed by RNase protection assays.
      ER beta.2 is initially expressed as maternally transmitted RNA, until 6 h after
      fertilization, when expression disappears. Between 6 and 48 h after
      fertilization, no ER expression could be observed. After 48 h after
      fertilization, all ERs, but predominantly ER alpha, began to be expressed. We
      conclude that oestrogen signal transduction can operate during zebrafish
      development only within discrete time windows.

PMID- 12063183
TI  - Comparative activity of pulsed or continuous estradiol exposure on gene
      expression and proliferation of normal and tumoral human breast cells.
AB  - Intranasal administration of hormone replacement therapy presents an original
      plasma kinetic profile with transient estrogen levels giving rise to the concept
      of pulsed therapy. To further understand the molecular effects of this new
      therapy, we have compared the effects of pulsed and continuous estradiol
      treatments on two critical aspects of estradiol action: gene expression and cell
      proliferation. Cells were stimulated with estradiol as 1-h pulsed or 24-h
      continuous treatments at concentrations such that the 24-h exposure
      (concentration x time) was identical in both conditions. In MCF7 cells, the
      transcriptional activity of estrogen receptors (ER) on a transiently transfected
      responsive estrogen response element-luciferase reporter construct was shown to
      be drastically (approximately 10-fold) and similarly stimulated after both
      treatments. Moreover, the increased mRNA expression of three representative
      estradiol-sensitive genes (pS2, cathepsin D, progesterone receptor), evaluated by
      Northern blot, was identical after 1-h pulse with 7 nM estradiol or continuous
      treatment with 0.29 nM estradiol with the same kinetic profile over 48 h.
      Proliferation was quantified by a histomorphometric method on primary cultures of
      human normal breast cells from reduction mammoplasties and using a fluorescence
      DNA assay in six human breast cancer cell lines which were ER positive or
      negative. After a 7-day treatment period, estradiol had no effect on the
      proliferation of the three ER negative cell lines (BT20, MDA MB231, SK BR3) but
      significantly stimulated the proliferation of the normal cells and of the three
      tumoral hormone-sensitive cell lines (MCF7, T47D, ZR 75-1); both hormone
      treatments producing the same increases in cell growth. In conclusion, we have
      shown that the genomic or proliferative effects of estradiol were identical with
      pulsed or continuous treatments, thus indicating that estrogenic effects are not
      strictly related to concentrations but rather to total hormone exposure.

PMID- 12063184
TI  - Identification of genes differentially regulated by glucocorticoids and
      progestins using a Cre/loxP-mediated retroviral promoter-trapping strategy.
AB  - Glucocorticoids and progestins are two classes of steroid hormone with very
      distinct biological functions. However, the glucocorticoid receptor (GR) and the
      progesterone receptor (PR) share many structural and functional similarities. One
      way that glucocorticoids and progestins can exert different biological effects is
      through their different abilities to regulate the expression of certain target
      genes. A strategy employing a retroviral promoter-trap and Cre/loxP-mediated site
      specific recombination has been developed to identify genes that are
      differentially regulated by glucocorticoids and progestins. A mouse fibroblast
      cell line (4F) stably expressing both GR and PR and containing a single copy of a
      multifunctional selection plasmid is generated. This line is transduced with a
      self-inactivating retroviral promoter-trap vector carrying coding sequences for
      Cre-recombinase (Cre) in the U3 region. Integration of the provirus places Cre
      expression under the control of a genomic flanking sequence. Activation of Cre
      expression from integration into active genes results in a permanent switch
      between the selectable marker genes that converts the cells from neomycin
      resistant to hygromycin-resistant. Selection for hygromycin resistance after
      hormone treatment yields recombinants in which Cre sequences in the U3 region are
      expressed from hormone-inducible upstream cellular promoters. Because Cre
      mediated recombination is a permanent event, the expression of the selectable
      marker genes is independent of ongoing Cre expression. Thus this system permits
      the identification of genes that are transiently or weakly induced by hormone.

PMID- 12063185
TI  - Hesx1 homeodomain protein represses transcription as a monomer and antagonises
      transactivation of specific sites as a homodimer.
AB  - The homeobox repressor Hesx1, expressed throughout Rathke's pouch and required
      for normal pituitary development, has been implicated in anterior pituitary
      pathogenesis in man. Prolonged expression of Hesx1 delays the appearance of
      anterior pituitary terminal differentiation markers in mice, particularly the
      gonadotroph hormones. We tested if Hesx1 could modulate gonadotrophin gene
      expression directly, and found that Hesx1 repressed both common alpha subunit
      (alpha GSU) and luteinising hormone beta-subunit (LH beta) gene promoters.
      Repression mapped to the Pitx1 homeodomain protein transactivation site in the
      proximal alpha GSU promoter, but did not map to the equivalent site on LH beta.
      Hesx1 repression of the alpha GSU Pitx1 site was overridden by co-transfection of
      Pitx1. In contrast, Hesx1 antagonised Pitx1 transactivation of LH beta in a dose
      dependent manner. This was due to monomeric binding of Hesx1 on alpha GSU and
      homodimerisation on LH beta. The homodimerisation site comprises the Pitx1 DNA
      binding site and a proximal binding site, and mutation of either inhibited
      homodimer formation. Conversion of the LH beta Pitx1 DNA binding site to an alpha
      GSU-type did not promote homodimer formation, arguing that Hesx1 has pronounced
      site selectivity. Furthermore, mutation of the proximal half of the
      homodimerisation site blocked Hesx1 antagonisation of Pitx1 transactivation. We
      conclude that Hesx1 monomers repress gene expression, and homodimers block
      specific transactivation sites.

PMID- 12063186
TI  - The effects of antisense insulin-like growth factor-I receptor oligonucleotide on
      human cord blood lymphocytes.
AB  - Our objective was to study the effects of type I insulin-like growth factor
      receptor (IGF-IR) on human cord blood lymphocyte (CBL) functions. First, we used
      RT-PCR to determine the expression of IGF-IR at the mRNA level in CBL. We then
      inhibited the expression of IGF-IR in CBL by the antisense oligonucleotide for
      the IGF-IR gene. We measured the changes in interleukin (IL)-2, -4 and interferon
      gamma (IFN gamma) at mRNA levels by RT-PCR, immunoglobulin M (IgM) production by
      CBL with an ELISA and lymphocyte proliferation by a (3)H-thymidine uptake
      technique. Our results showed that IGF-IR mRNA was detected in both non-activated
      and activated CBL, but the expression levels in the activated CBL were higher
      than those in the non-activated CBL. After being exposed to the antisense
      oligonucleotide, a 50% reduction in the amount of IGF-IR mRNA occurred.
      Accordingly, the proliferation of CBL to mitogen was significantly reduced about
      50%, and the production of IgM from CBL was also markedly decreased. In the
      phytohemagglutinin-stimulated CBL culture system, when the IGF-IR antisense
      oligonucleotide existed, the mRNA levels of IFN gamma and IL-2 decreased 30-50%
      and IL-4 decreased 20-30%. We concluded that IGF-IR is most likely involved in
      the process of CBL proliferation and production of immunoglobulin and cytokines.
      It might therefore play an important role in the modulation of the immune
      functions.

PMID- 12063187
TI  - Differential expression of secreted frizzled-related protein 4 in decidual cells
      during pregnancy.
AB  - During pregnancy, the uterus shows marked morphological and physiological changes
      under the regulation of ovarian steroid. To elucidate the molecular cues of these
      changes, we tried to identify the transcripts differentially expressed in the
      pregnant rat uterus by using the suppression subtractive hybridization method.
      Seven independent clones were isolated and one of the up-regulated genes was
      secreted frizzled-related protein 4 (sFRP4). sFRP4 contains a Wnt-binding domain
      and belongs to the secreted frizzled protein family whose members are assumed to
      function as modulators of the Wnt signal. The expression level of sFRP4 mRNA
      reached a peak in the pregnant uterus on day 12, when uterine decidualization was
      almost complete in the rat. In situ hybridization histochemistry revealed that
      sFRP4 transcripts were observed in the decidual cells. In addition, proliferating
      cell nuclear antigen (PCNA)-positive cells were shown to be overlapped in
      decidua, suggesting that sFRP4 mRNA expression was accompanied by the late phase
      of decidual cell proliferation. Moreover, sFRP4 and estrogen receptor-alpha
      transcripts were co-localized. Furthermore, we analyzed the regulation of sFRP4
      by estrogen using 17 beta-estradiol-treated ovariectomized rats. sFRP4 mRNA was
      detected in the uterus at 48 h after estrogen treatment, especially in
      endometrial stroma where PCNA-positive cells were also observed. The results in
      this study led us to the notion that sFRP4 mRNA may be up-regulated after
      estrogen treatment in the late phase of uterine cell proliferation.

PMID- 12063190
TI  - Our compact with tomorrow's doctors.
AB  - In recent years, the image of medicine as a caring profession has been badly
      tarnished by a rash of critical reports in the media. In the face of this
      negative publicity, do young people still want to be doctors? The author reviews
      conventional reasons given for the declining applicant pool (e.g., issues of
      declining income, loss of autonomy, etc.) and posits that an additional reason
      may be perceptions that doctors no longer command respect and that they are being
      oppressed by, rather than being guardians of, the health care system. Such views
      challenge academic medicine to broadcast to the world a realistic picture of the
      fabulous opportunities and gratifications that lie ahead for the next generation
      of physicians. However, academic medicine must also address some current
      realities within medical education, such as the admission process (where at
      present there is a tendency to overemphasize indices of academic achievement and
      underemphasize the personal characteristics sought in applicants) and the
      acculturation process in medical school (which can often dehumanize students and
      convert idealistic ones into cynics). The author acknowledges that these are
      tough challenges. He suggests as a first step that leaders of academic medicine
      prepare and disseminate an explicit statement of their commitments, a kind of
      compact between teachers and learners of medicine. He outlines these commitments,
      and states his hope that by fulfilling them, the academic medicine community can
      make clear that medicine-which at its core is still about the doctor-patient
      relationship-is a true calling, not just beleaguered occupation.

PMID- 12063188
TI  - Chicken neuropeptide Y-family receptor Y4: a receptor with equal affinity for
      pancreatic polypeptide, neuropeptide Y and peptide YY.
AB  - Within the neuropeptide Y (NPY) family of peptides, pancreatic polypeptide is the
      most divergent across species. It differs in 20 of 36 positions between human and
      chicken. In mammals, it binds primarily to the Y4 receptor, to which NPY and
      peptide YY (PYY) bind with lower affinities. Because of these large sequence
      differences in pancreatic polypeptide, we decided to characterise the chicken Y4
      receptor. We report here that Y4 displays the least sequence conservation among
      the Y-family receptors, with only 57-60% overall amino acid identity between
      chicken and mammals, compared with 64-83% for the Y1, Y2 and Y5 receptors. After
      expression of the chicken Y4 receptor in COS-7 cells, (125)I-labelled porcine (p)
      PYY bound with a K(d) of 20 pM. In competition with (125)I-pPYY, chicken
      pancreatic polypeptide bound with high affinity at 140 pM. Interestingly, chicken
      PYY bound with even greater affinity at 68 pM. The affinity of NPY, 160 pM, was
      similar to that of pancreatic polypeptide. Chicken Y4 is less sensitive than is
      mammalian Y4 to truncation of the amino terminus of the NPY molecule. RT-PCR
      revealed expression in several peripheral organs, including adipose tissue and
      oviduct. In brain, Y4 mRNA was detected in the brainstem, cerebellum and
      hippocampus. In situ hybridisation to brain sections showed expression in the
      dorsal motor nucleus of the vagus in the brainstem. Thus the chicken Y4 receptor
      is less selective and anatomically more widespread than that in mammals, probably
      reflecting the original properties of the Y4 receptor.

PMID- 12063191
TI  - Understanding social influence in medical education.
AB  - Many aspects of the medical education system lead trainees to a host of
      maladaptive reactions and behaviors, but far too little attention has been
      focused on the impact that interactions between teacher and learner can have on
      the development of professionalism. The authors discuss the concept of "social
      influence," a change of attitude, belief, or behavior resulting from the actions
      of another person in the context of the medical education setting. Using the
      example of a medical student who has not adequately completed his inpatient
      medicine requirements, they identify ten strategies of social influence that a
      medical educator might invoke to change the student's behavior and evaluate the
      benefits and drawbacks of these strategies. This overview can be used by faculty
      to explore new strategies of teaching and to reflect on their current teaching
      styles.

PMID- 12063192
TI  - Evaluating physicians' professionalism and humanism: the case for humanism
      "connoisseurs".
AB  - Physicians' professionalism and humanism have become central foci of the efforts
      of medical educators as the public, various accrediting and licensing agencies,
      and the profession itself have expressed concerns about the apparent erosion of
      physicians' competency in these aspects of the art, rather than the science, of
      medicine. Of the many obstacles to enhancing trainees' skills in these domains,
      one of the most significant is the difficulty in assessing competency in
      physicians' professionalism and humanism. The author suggests that the assessment
      of these aspects of the art of medicine has more in common with the approaches
      used in criticism of the arts than with the quantitative assessment tools
      appropriate to the scientific method and the medical model. Quantitative and semi
      quantitative tools, so effective in elucidating the etiology, pathophysiology,
      and treatment of disease, are often in-appropriate and invalid when applied to
      evaluation of professional and humanistic competencies. The author proposes that
      humanism "connoisseurs" be employed to qualitatively evaluate medical trainees'
      professionalism and humanism. Such connoisseurs would possess expert knowledge,
      training, and experience in the interpersonal aspects of the art of medicine,
      allowing them to deconstruct concepts such as empathy, compassion, integrity, and
      respect into their respective key elements while evaluating physicians' behaviors
      as an integrated, cohesive whole. Through the use of a rich descriptive
      vocabulary, humanism connoisseurs would provide valid formative and summative
      feedback regarding competency in medical professionalism and humanism. In the
      process, they would serve to counteract the relative marginalization of
      professionalism and humanism in the informal and lived curricula of medical
      trainees.

PMID- 12063193
TI  - The House of God : another look.
AB  - Since its publication in 1978, Samuel Shem's The House of God has sold over two
      million copies in over 50 countries. While it has remained popular among medical
      students, its value as a literary text to promote critical reflection on self and
      profession continues to be unrecognized in professional spheres. In spite of the
      ongoing conditions in medical training that prompted Shem's satirical novel, The
      House of God continues to evoke negative responses from academic medicine and has
      even been dismissed as "dated." This article examines the novel, its reception by
      academic medicine, and the relevance of its satire through an analyses of
      articles, reviews, and letters, along with Shem's observations on the novel and
      its controversies. Finally, the future of The House of God is proposed.

PMID- 12063194
TI  - Assessing professional behavior: yesterday, today, and tomorrow.
AB  - PURPOSE: The author interprets the state of the art of assessing professional
      behavior. She defines the concept of professionalism, reviews the psychometric
      properties of key approaches to assessing professionalism, conveys major findings
      that these approaches produced, and discusses recommendations to improve the
      assessment of professionalism. METHOD: The author reviewed professionalism
      literature from the last 30 years that had been identified through database
      searches; included in conference proceedings, bibliographies, and reference
      lists; and suggested by experts. The cited literature largely came from peer
      reviewed journals, represented themes or novel approaches, reported qualitative
      or quantitative data about measurement instruments, or described pragmatic or
      theoretical approaches to assessing professionalism. RESULTS: A circumscribed
      concept of professionalism is available to serve as a foundation for next steps
      in assessing professional behavior. The current array of assessment tools is
      rich. However, their measurement properties should be strengthened. Accordingly,
      future research should explore rigorous qualitative techniques; refine
      quantitative assessments of competence, for example, through OSCEs; and evaluate
      separate elements of professionalism. It should test the hypothesis that
      assessment tools will be better if they define professionalism as behaviors
      expressive of value conflicts, investigate the resolution of these conflicts, and
      recognize the contextual nature of professional behaviors. Whether measurement
      tools should be tailored to the stage of a medical career and how the environment
      can support or sabotage the assessment of professional behavior are central
      issues. FINAL THOUGHT: Without solid assessment tools, questions about the
      efficacy of approaches to educating learners about professional behavior will not
      be effectively answered.

PMID- 12063195
TI  - The anatomy of the professional lapse: bridging the gap between traditional
      frameworks and students' perceptions.
AB  - PURPOSE: To support students' developing professionalism, it is necessary to
      understand the professional challenges and dilemmas they perceive in the clinical
      setting. This study systematically documented and catalogued students' reports of
      professional lapses. METHOD: Six focus groups were conducted with senior medical
      students (n = 29) at three universities. Using a grounded-theory approach, three
      researchers analyzed the students' reports of specific lapses in professionalism
      for recurrent themes. The resulting coding structure was applied using NVivo
      qualitative data analysis software. RESULTS: A total of 120 pages of text yielded
      48 specific incidents of professional lapses, which were analyzed by three
      researchers using grounded theory. Most incidents were witnessed (n = 34) or
      known about (n = 4), as opposed to self-reported (n = 10). Six critical "issues"
      emerged: communicative violations (to or about patients or other health care
      professionals); role resistance (individuals chafing against constraints or
      expectations of their perceived roles); objectification of patients (ignoring
      patients or treating patients as vehicles for learning); accountability (to
      colleagues or patients, including avoiding patients, failing to disclose
      information, or failing to treat appropriately); physical harm (to patients or
      others); and crossfire (being put in the middle of a struggle between superiors).
      CONCLUSIONS: This study explored how students experienced and operationalized
      professionalism in clinical settings at a variety of universities. Interestingly,
      the critical issues they reported as salient did not map easily onto standard,
      abstract definitions of professionalism. This incongruence suggested that the
      development of effective curricula in this domain must bridge the gap between
      traditional taxonomies and students' perceptions of professionalism.

PMID- 12063196
TI  - Using the American Board of Internal Medicine's "Elements of Professionalism" for
      undergraduate ethics education.
AB  - PURPOSE: To examine the feasibility of using the taxonomy of professional and
      unprofessional behaviors presented in the American Board of Internal Medicine's
      (ABIM's) Project Professionalism to categorize ethical issues that undergraduate
      medical students perceive to be salient. METHOD: Beginning second-year medical
      students at the University of Washington School of Medicine (n = 120) were asked
      to respond to three open-ended questions about professional standards of conduct
      and peer evaluation. Two of the authors read and coded the students' responses
      according to the ABIM's elements of professionalism (altruism, accountability,
      excellence, duty, honor and integrity, and respect for others) and the challenges
      to those elements (abuse of power, arrogance, greed, misrepresentation,
      impairment, lack of conscientiousness, and conflict of interest). Coding
      disagreements were solved using review and revision of the category definitions.
      New categories were created for students' responses that described behaviors or
      issues that were not captured in the ABIM's categories. RESULTS: A total of 114
      students responded. The ABIM's professional code was adapted for students and
      teachers, making it context- and learning-stage-specific. One new category of
      challenges, conflicts of conscience, was added, and one category (abuse of power)
      was expanded to include abuse of power/negotiating power asymmetries.
      CONCLUSIONS: Using the ABIM's taxonomy to name professional and unprofessional
      behaviors was particularly useful for examining undergraduate medical students'
      perceptions of the ethical climate for learning during the first year of medical
      school, and it holds promise for research into changes in students' perceptions
      as they move into clinical experiences. Using the framework, students can build a
      unified professional knowledge-and-skills base.

PMID- 12063197
TI  - Medicine and the arts. The Secret Agent .

PMID- 12063199
TI  - Specialty board certification and clinical outcomes: the missing link.
AB  - PURPOSE: Specialty board certification status is often used as a standard of
      excellence, but no systematic review has examined the link between certification
      and clinical outcomes. The authors evaluated published studies tracking clinical
      outcomes and certification status. METHOD: Data sources consisted of studies
      cited between 1966 and July 1999 in OVID-Medline, psychological abstracts
      (PsycLit), and the Educational Research Information Clearinghouse (ERIC).
      Screening criteria included: only U.S. patients and physicians used as subjects;
      verified specialty board certification status by an American Board of Medical
      Specialties' (ABMS') member board using the ABMS database or derivative sources;
      described selection criteria for patients and physicians; selected nationally
      recognized standards of care for outcomes; and nested patient data by individual
      physician. The computerized searches that were conducted in 1999 identified 1,204
      papers; one author and a research assistant selected 237 papers based on subject
      relevance, and reduced the list to 56 based on study quality. The authors
      independently applied inclusion and exclusion criteria to identify 13 of the 56
      papers containing 33 separable relevant findings. RESULTS: Of the 33 findings, 16
      demonstrated a significant positive association between certification status and
      positive clinical outcomes, three revealed worse outcomes for certified
      physicians, and 14 showed no association. Three negative findings and one finding
      of no association were identified in two papers with insufficient case-mix
      adjustments in the analyses. Meta-analytic statistics were not feasible due to
      variability in outcome measures across studies. CONCLUSIONS: Few published
      studies (5%) used research methods appropriate for the research question, and
      among the screened studies more than half support an association between board
      certification status and positive clinical outcomes.

PMID- 12063201
TI  - Clerkship directors' perceptions of the impact of HCFA documentation guidelines.
AB  - PURPOSE: Chart notes are used to support billing codes under the evaluation and
      management guidelines of the Health Care Financing Administration (HCFA), in
      addition to serving as a record of the visit. To better understand the effect of
      the HCFA documentation guidelines, the authors collected data on how the
      guidelines affect participation by university- and community-based faculty in
      clinical education programs. METHOD: In 2000, the authors sent six copies of
      their questionnaire to the associate deans of the 125 U.S. medical schools and
      requested they distribute them to all core clerkship directors. The questionnaire
      consisted of multiple-choice and short-answer questions regarding documentation
      of medical visits, participation of community-based faculty, understanding of
      HCFA documentation guidelines, and effects on education programs. RESULTS: The
      response rate was about 50%. Most of the 379 clerkship directors who responded
      (77%) stated they were aware the HCFA documentation guidelines include
      specifications regarding the role medical students can play and documentation of
      medical visits, and 64% indicated they were concerned the guidelines would affect
      their educational programs. Concerns included the loss of student independence
      and active participation in the patient care environment (37), time constraints
      and the changing balance between education and service (16), loss of faculty and
      decreased morale (11), and decreased quality of care for patients (7).
      CONCLUSION: Leaders of medical education must work to modify these guidelines to
      protect the quality of patients' care, while maximizing students' educational
      opportunity and participation.

PMID- 12063202
TI  - A model for assessing information retrieval and application skills of medical
      students.
AB  - PURPOSE: To develop and evaluate a model for assessing information retrieval and
      application skills, and to compare the performances on the assessment exercises
      of students who were and were not instructed in these skills. METHOD: The authors
      developed a set of four examination stations, each with multiple subtasks, and
      administered the exams to students at two medical schools. Students at one school
      had intensive instruction in literature searching and filtering skills for
      information quality (instructed group), and those at the other school had minimal
      instruction in these areas (uninstructed group). The stations addressed
      pediatrics content and the skills of searching Medline and the World Wide Web,
      evaluating research articles, evaluating the accuracy of information from the
      Web, and using the information to make recommendations to patients. The authors
      determined the psychometric characteristics of the stations and compared the
      performances of the two groups of students. RESULTS: Students in the instructed
      group performed significantly better and with less variability than the
      uninstructed group on four tasks and no differently on seven tasks. There was no
      task on which the uninstructed group performed significantly better than the
      instructed group. CONCLUSION: The prototype stations showed predictable
      differences across curricula, indicating that they have promise as assessment
      tools for the essential skills of information retrieval and application.

PMID- 12063203
TI  - A model of how students link problem-based learning with clinical experience
      through "elaboration".
AB  - PURPOSE: In 1994, the medical school at the University of Manchester introduced a
      new integrated course that uses problem-based learning (PBL) throughout the
      clinical clerkships as the major approach for delivery of the core curriculum.
      This study explored how students linked PBL and clinical experiences. METHOD: All
      third- and fourth-year students were asked to respond to an open-ended question
      on the end-of-module course evaluation. Their responses were analyzed and grouped
      into themes. The authors also conducted three focus groups of third-year students
      and a further three focus groups of fourth-year students to explore how students
      viewed the links between PBL and clinical experiences. The discussions were taped
      and subsequently analyzed by the researchers independently. RESULTS: The authors
      found that the students used clinical experience as a means of elaborating their
      knowledge either at the time of encountering an appropriate patient (outside the
      group) or by bringing their experiences back to the PBL group for discussion
      (inside the group). Major facilitators of elaboration were the match between the
      clinical clerkship and the content of the PBL case, the role of the tutor, and
      the self-directedness of the student. A theoretical model of how students linked
      PBL with their clinical experience was derived based on a cognitive psychological
      approach to learning. CONCLUSIONS: The model will be of benefit as the authors
      try to improve the course for those students who were unable to use their
      clinical experiences to achieve the goals of their PBL discussions.

PMID- 12063205
TI  - The spirituality of academic physicians: an ethnography of a Scripture-based
      group in an academic medical center.
AB  - Whether acknowledged or not, spirituality is part of the human condition of
      physicians as well as patients, and of the distinctive work that doctors do. This
      paper presents a first-hand sociological account of a group of 20 academic
      physicians in a large, urban, East Coast academic medical center who met weekly
      to study theological concepts drawn from Christian Scripture. The principal
      method of inquiry was participant observation over the course of an academic
      year. In analyzing the "talk" and interaction that took place among them, the
      authors observed not only some of the implicit tensions between medicine,
      religion, and spirituality but also the complementarity between them. While the
      group's explicit purpose was to foster spiritual growth and connectedness, it
      also provided a venue in which members dealt openly with problems of uncertainty
      and meaning that the practice of medicine inevitably raises; with the meaning of
      physicianhood, given the growing corporatization of medicine; with an opportunity
      to engage in "worried consultation" with their spiritual-medical colleagues about
      their mutual patients; and to underscore for each other their dismay about the
      absence of spirituality in medicine, on the one hand, and their belief about its
      importance on the other. The authors also highlight some of the ways in which
      spirituality influenced these physicians' medical outlook, and conversely, how
      that outlook shaped their mode of spiritual reflection.

PMID- 12063206
TI  - Evaluating knowledge retention of third-year medical students taught with an
      innovative pharmacology program.
AB  - PURPOSE: To explore the degree of retention of pharmacologic knowledge of third
      year medical students taught in a new pharmacology teaching program. METHOD: In
      1997, the authors administered a retention test consisting of 100 multiple-choice
      questions, each with only one correct answer, to 457 third-year medical students
      at the National University of Mexico. Students were not told in advance about
      this diagnostic evaluation, which was given eight months after they completed the
      second-year pharmacology course. As a comparison, the authors also analyzed the
      results obtained by the same students in the three partial examinations taken
      during the second-year pharmacology course. The Kolmogorov-Smirnov procedure and
      Wilcoxon and chi-square tests were used to analyze data. RESULTS: The
      distribution of scores obtained in the partial exams well approximated a
      symmetrical bell-shaped curve, and the mean score was 59.9%. In contrast, in the
      retention test the distribution was negatively skewed, the mean score (69.8%) was
      significantly higher (p <.001), and the curve was clearly displaced to the right
      of that corresponding to the partial exams. The percentage of students obtaining
      at least a passing score (60%) was considerably higher for the retention test
      (82.5 versus 51.9). CONCLUSION: These findings, indicating that medical students
      taught in a new pharmacology program developed adequate basic pharmacologic
      knowledge, should encourage other medical schools to formally evaluate their
      teaching programs and continue efforts to improve pharmacologic education of
      medical students.

PMID- 12063209
TI  - Students' attitudes toward indigent patients.
AB  - Second- and fourth-year medical students were surveyed about the influence of
      medical education on their attitudes towards indigent patients and its role in
      career planning.

PMID- 12063207
TI  - Implementation and evaluation of an undergraduate Sociocultural Medicine Program.
AB  - PURPOSE: To demonstrate an effective model for designing, implementing, and
      evaluating the Sociocultural Medicine Program (SMP), part of a comprehensive
      sociocultural medicine curriculum at the University of Michigan Medical School.
      METHOD: This study followed a cross-sectional, pre- and post-intervention survey
      design. A total of 167 medical students completed a measure of attitudes toward
      sociocultural issues in medicine prior to and following participation in the SMP.
      Students' attitudes were assessed in the domains of "exposure to sociocultural
      issues," "sociocultural factors in clinical scenarios," and "sociocultural
      background in patient/physician/health status issues." RESULTS: Paired t-tests of
      the pre- and post-intervention responses revealed significant positive changes
      for items in the domain of exposure to sociocultural issues in medicine:
      experience with sociocultural issues in a clinical setting (p <.01),
      understanding of relationship among sociocultural background, health, and
      medicine (p <.001), and importance of sociocultural background in students'
      future patient populations (p <.01). Significant changes were also found for the
      impact of sociocultural background in patient/physician/health status issues:
      physician-patient relationship (p <.001) and patients' health behavior (p <.001).
      CONCLUSIONS: The SMP had a significant educational impact on students' attitudes
      towards sociocultural issues in medicine. Students reported greater exposure to
      these issues conceptually and clinically, and greater influence of sociocultural
      factors in patients' behaviors and patient- physician relationships. Critical
      components of this SMP were faculty development, multiple teaching approaches,
      and pre- and post-intervention evaluation.

PMID- 12063210
TI  - Results of the National Resident Matching Program for 2002.

PMID- 12063211
TI  - Mass screening for retrocochlear disorders.

PMID- 12063212
TI  - Diffusion tensor MR imaging of gray matter in different multiple sclerosis
      phenotypes.

PMID- 12063213
TI  - Proton magnetic resonance spectroscopy of the thalamus in patients with chronic
      neuropathic pain after spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Spinal cord injury (SCI) results in a number of
      consequences; one of the most difficult to manage is chronic neuropathic pain.
      Thus, defining the potential neural and biochemical changes associated with
      chronic pain after SCI is important because this may lead to development of new
      treatment strategies. Prior studies have looked at the thalamus, because it is a
      major sensory relay station. The purpose of our study was to define alterations
      in metabolites due to injury-induced functional changes in thalamic nuclei by
      using single-voxel stimulated echo acquisition mode MR spectroscopy. METHODS:
      Twenty-six men were recruited: 16 patients with SCI and paraplegia (seven with
      pain, nine without pain) and 10 healthy control subjects. Pain was evaluated in
      an interview, which included the collection of information concerning the
      location, quality, and intensity of pain, carefully identifing the dysesthetic
      neuropathic pain often seen in SCI. Localized single-voxel (8-cm(3) volume)
      proton spectra were acquired from the left and right thalami. RESULTS: The
      concentration of N-acetyl (NA) was negatively correlated with pain intensity (r =
      -0.678), and the t test showed that NA was significantly different between
      patients with pain and patients without pain (P =.006). Myo-inositol was
      positively correlated with pain intensity (r = 0.520); difference between
      patients with pain and those without pain was almost significant (P =.06).
      CONCLUSION: The observed differences in metabolites in SCI patients with and pain
      and in those without pain suggest anatomic, functional, and biochemical changes
      in the thalamic region.

PMID- 12063214
TI  - Diffusion-weighted MR imaging of metastatic disease of the spine: assessment of
      response to therapy.
AB  - BACKGROUND AND PURPOSE: In cases of metastatic disease of the spine, monitoring
      the response to medical therapy with plain radiography, bone scanning, and
      conventional spin-echo sequence MR imaging is unsatisfactory because of the
      insensitivity or nonspecific findings of these imaging modalities. The purpose of
      this study was to investigate signal intensity changes of bone marrow after
      therapy by using diffusion-weighted MR imaging to monitor the response to medical
      therapy in cases of metastatic disease of the spine. METHODS: Twenty-four
      patients with metastatic disease of the spine were examined with MR imaging.
      Diffusion-weighted MR imaging and spin-echo MR imaging were performed in all
      patients before and after radiation therapy. Follow-up diffusion-weighted MR
      imaging and spin-echo MR imaging were performed for comparison purposes in nine
      cases at 1 month, in seven cases at 2 months, in seven cases at 3 months, and in
      three cases at 6 months after therapy. The diffusion-weighted MR imaging
      sequences were based on a steady-state free precession with a low b value (165
      s/mm(2)) and a single shot stimulated echo-acquisition mode with a high b value
      (650 s/mm(2)). Apparent diffusion coefficient maps were obtained using two
      different b values incorporated in a diffusion-weighted single shot stimulated
      echo-acquisition mode sequence. Apparent diffusion coefficient maps were obtained
      in three cases. Signal intensity changes of the metastatic disease of the
      vertebral bone marrow before and after therapy on conventional spin-echo sequence
      and diffusion-weighted MR images were evaluated. RESULTS: As shown by diffusion
      weighted MR imaging, metastatic disease of the vertebral bone marrow included in
      our study before therapy was hyperintense to normal vertebral bodies. In 23
      patients with clinical improvement, metastatic disease of the spine after therapy
      was hypointense relative to normal vertebral bodies on the follow-up diffusion
      weighted MR images. In one patient with hepatocellular carcinoma, the clinical
      symptoms did not improve and follow-up bone scanning performed 6 months after
      therapy showed increased uptake. Persistent hyperintense bone marrow after
      therapy was also noted on diffusion-weighted MR images. Decreased signal
      intensity of the metastatic disease of the spine on diffusion-weighted MR images
      was observed >1 month after therapy. CONCLUSION: Diffusion-weighted MR imaging
      shows that, with successful therapy, there is decreased signal intensity of
      metastatic disease of the vertebral bone marrow.

PMID- 12063215
TI  - Is percutaneous vertebroplasty without pretreatment venography safe? Evaluation
      of 205 consecutives procedures.
AB  - BACKGROUND AND PURPOSE: Vertebral venography has been advocated before bone
      cement injection when performing percutaneous vertebroplasty (PV) for benign or
      malignant lesions of the spine. Although venography can document sites of
      potential leakage during subsequent cement application, stagnant contrast agent
      renders the cement injection more difficult to monitor, and an allergic reaction
      to contrast agent remains a potential risk. We evaluated our experience with PV
      without prior venographic evaluation. METHODS: Two hundred five consecutive PV
      procedures performed in 137 patients without pretreatment venography were
      evaluated for complications linked to bone cement injection. Treated lesions were
      172 benign compression fractures, 27 metastases, two hemangiomas, and four
      multiple myelomas. PV was performed with a single-pedicle technique in 146 cases
      and a two-pedicle technique in 59 cases. RESULTS: No major complication occurred
      in our series. Three minor complications (1.5%) were documented: One patient had
      a transient episode of arterial hypotension during cement injection, without
      cement leak; one patient had a spontaneously resolving patch of cutaneous
      hypoesthesia at the puncture site; and one patient had a radiculopathy four
      levels above the treated level, not caused by cement deposition, and successfully
      treated with a nerve block. None of these three minor complications were related
      to cement leakage. CONCLUSION: PV can, in our experience, be performed safely
      without prior angiographic evaluation of the vertebral venous system.

PMID- 12063216
TI  - Mass screening for retrocochlear disorders: low-field-strength (0.2-T) versus
      high-field-strength (1.5-T) MR imaging.
AB  - BACKGROUND AND PURPOSE: In patients with clinical symptoms suggestive of a
      retrocochlear disorder, contrast-enhanced T1-weighted spin-echo (SE) high-field
      strength MR imaging is considered the criterion standard in assessing vestibular
      schwannoma. However, only 10-20% of its findings are pathologic. Our purpose was
      to prospectively compare the performance of low-field-strength MR imaging in
      screening for retrocochlear disorders, with high-field-strength MR imaging as the
      criterion standard. METHODS: A total of 287 patients with suspected retrocochlear
      disease underwent axial 1.5-T MR imaging with a T1-weighted SE sequence before
      and after contrast enhancement and with a high-resolution T2-weighted
      construction interference in steady state sequence. At immediate follow-up, the
      same patients underwent axial 0.2-T T1-weighted SE imaging without additional
      contrast enhancement. Results were classified as negative, positive, or uncertain
      and were analyzed in light of the patients' clinical symptoms. RESULTS: MR
      imaging at 1.5 T depicted 63 disorders (21.95%), including 53 schwannomas, three
      other tumors, and seven other disorders (ie, gadolinium-enhancing inner ear,
      facial nerve, or meninges). MR imaging at 0.2 T showed evidence of 58 disorders;
      five disorders were not detected, although all schwannomas and other tumors were
      seen, including those smaller than 2 mm, and only two (28.6%) of the other
      disorders were detected. When correlated with clinical data, results showed that
      the five undetected disorders occurred in patients with unusual clinical signs.
      CONCLUSION: MR imaging at 0.2 T provided high sensitivity in detecting vestibular
      schwannoma of the internal auditory canal or cerebellopontine angle; it can be
      used for mass screening for this disease. Positive and uncertain imaging findings
      should be followed up with high-field-strength MR imaging.

PMID- 12063217
TI  - Evaluation of distal extracranial internal carotid artery by transoral carotid
      ultrasonography in patients with severe carotid stenosis.
AB  - BACKGROUND AND PURPOSE: Conventional ultrasonography techniques do not allow
      visualization of the distal cervical segment of the internal carotid artery
      (ICA). In a study of patients with severe ICA stenosis, we performed transoral
      carotid ultrasonography (TOCU) to assess its ability to image this segment of the
      artery. METHODS: The study participants consisted of 20 consecutive patients who
      had severe carotid stenosis and who underwent carotid endarterectomy between 1999
      and 2000. TOCU, conventional carotid ultrasonography, and cerebral angiography
      were prospectively performed before and after carotid endarterectomy. RESULTS: In
      all patients, the distal portion of the ICA could be clearly detected by B mode
      using TOCU and no plaque was observed. The diameter of the distal portion of the
      ICA significantly increased after carotid endarterectomy (3.9 +/- 0.5 mm [mean +/
      SD]), compared with before (3.5 +/- 0.8 mm), when it was estimated by TOCU (P
      <.01). In seven patients, the postoperative diameter of the distal ICA increased
      >10%. The mean increase in the postoperative diameter was estimated to be 15.0 +/
      23.0% by TOCU, which significantly correlated with the findings (23.9 +/- 33.7%)
      based on cerebral angiography (P <.01). The diameter increased >10%
      postoperatively in 71% of the patients with the degree of cross-sectional
      stenosis >95% as shown by carotid ultrasonography and in 86% of the patients
      whose preoperative diameter was <3.0 mm. CONCLUSION: TOCU provides additional
      information regarding the characteristics of the distal ICA that can be obtained
      neither by conventional carotid ultrasonography nor by angiography.

PMID- 12063218
TI  - Agenesis of the internal carotid artery associated with aortic arch anomaly in a
      patient with congenital Horner's syndrome.
AB  - We report a rare case of agenesis of the left internal carotid artery (ICA) and
      an aortic arch anomaly that presented with ipsilateral congenital Horner's
      syndrome. Digital subtraction angiography revealed left ICA agenesis shortly
      after its origin and anastomosis between the left maxillary artery and the
      supraclinoid segment of the left ICA. Aortography of the aortic arch revealed the
      right subclavian artery arising as the first branch of a left aortic arch,
      followed by a bicarotid trunk and a left subclavian artery. High resolution CT of
      the skull base revealed the absence of the left carotid channel, consistent with
      congenital agenesis of the ICA.

PMID- 12063219
TI  - Indolent intracranial mucormycosis: case report.
AB  - We present a patient with isolated intracranial mucormycosis that remained
      indolent for several months. The mucormycosis formed a mass in the prepontine
      cistern, probably spreading from the sphenoid sinus. We propose that at least
      some cases of what is considered isolated CNS mucormycosis develop from such
      unrecognized indolent infections. Mucormycosis may present as a mass in the
      basilar cisterns, especially in immunocompromised patients.

PMID- 12063220
TI  - Plain film imaging of Baerveldt glaucoma drainage implants.
AB  - A glaucoma drainage implant was detected on plain skull radiographs before MR
      imaging examination of the brain. The patient was denied the MR imaging for fear
      of dislodging the "metallic foreign body." The Baerveldt glaucoma drainage
      implant was mistakenly identified as an orbital metallic object based on its
      radiographic characteristics. Because none of the current glaucoma drainage
      implants contain ferromagnetic material, patients with these devices can undergo
      MR imaging without special precaution.

PMID- 12063221
TI  - Effect of glacial acetic acid and ethiodized oil concentration on embolization
      with N-butyl 2-cyanoacrylate: an in vivo investigation.
AB  - BACKGROUND AND PURPOSE: Precise control of the polymerization dynamics of
      cyanoacrylate mixtures used in the embolization of cerebral arteriovenous
      malformations is required to achieve a safe and permanent obliteration of the
      lesion. In this study, in vivo embolization using mixtures of Histoacryl,
      Lipiodol Ultra-Fluid, and glacial acetic acid (GAA) was investigated. The present
      study investigated whether increased ethiodized oil concentration or the addition
      of GAA increased rate of embolization. METHODS: Using embolic mixtures containing
      Histoacryl (N-butyl 2-cyanoacrylate [NBCA]), the embolization process in the
      femoral and subclavian arteries of the rabbit was examined. Various embolic
      agents composed of ethiodized oil and N-BCA mixtures, either with or without the
      addition of minute quantities of GAA, were injected. Blood flow through the
      aforementioned arteries was measured during embolization. The transient decay of
      blood flow to zero was modeled, and an optimized model parameter, termed the time
      elapsed to flow arrest (TEFA) factor, was compared with the experimental data
      related to the embolization process. RESULTS: The TEFA factor was independent of
      the variation of the ethiodized oil concentration in the mixture (P >.05). In
      contradistinction, the addition of GAA significantly increased the TEFA factor (P
      <.05). Moreover, a linear relation between the TEFA factor and the quantity of
      GAA in the mixture was discerned. CONCLUSION: Predictable control of the
      embolization process with N-BCA in vivo is attained by varying the amount of GAA
      in the embolic mixture.

PMID- 12063222
TI  - Cerebral microarteriovenous malformations: diagnostic and therpeutic features in
      a series of patients.
AB  - BACKGROUND AND PURPOSE: Few collected series of cerebral microarteriovenous
      malformations (micro-AVMs) have been reported. Our propose was to assess the
      unique diagnostic and therapeutic challenges posed by these lesions and their
      influence on outcomes. METHODS: The clinical presentation, diagnostic features,
      principles of endovascular or surgical treatment, and outcomes for a consecutive
      series of 10 patients (five male, five female; mean age, 48.8 years; age range,
      31-65 years) with angiographically demonstrated cerebral micro-AVMs were
      retrospectively analyzed. RESULTS: All patients presented with a cerebral
      hematoma (supratentorial in eight, infratentorial in two, intraventricular in
      one, subarachnoid in one; mean volume, 11.6 cm(3)), which was superficially
      situated in nine patients. Neurologic deficits were observed in nine patients,
      and three patients had seizures. The mean delay between the onset of symptoms and
      diagnosis was 129.8 days (range, 6 days to 1 year). Superselective angiography
      was performed in seven patients and followed by successful acrylic embolization
      of the lesion in five. Five patients underwent surgical intervention, which led
      to definitive resection. Although long-term neurologic problems were present in
      eight patients, they were able to return to their previous activities and
      employment. CONCLUSION: The diagnosis of cerebral micro-AVMs requires a high
      index of suspicion, especially in young adults with atypical hemorrhaging. Single
      shot embolization of micro-AVMs may be a safe alternative to the established
      surgical therapy in select cases. Outcomes depend mostly on the clinical
      conditions at admission.

PMID- 12063223
TI  - Endovascular treatment of Hunt and Hess grade IV and V aneuryms.
AB  - BACKGROUND AND PURPOSE: Controversy still surrounds the question of when and how
      to manage cases of subarachnoid hemorrhage of Hunt and Hess grade IV and V
      aneurysms. Several authors are in favor of surgical treatment, reporting improved
      clinical outcomes and lower mortality rates. Considering that endovascular
      procedures are currently being increasingly used to treat aneurysms, we
      investigated their use in the management of subarachnoid bleeding in a
      retrospective review of 80 patients. METHODS: Eighty patients were admitted to
      our hospital between October 1992 and October 1998 with subarachnoid hemorrhage
      of Hunt and Hess grade IV and V aneurysms. Patients received standard
      resuscitation treatment, nimodipine to prevent vasospasm, CSF shunt when
      necessary, and selective occlusion with Guglielmi detachable coil. They were
      subsequently followed up for at least 1 year. Aneurysm occlusion was monitored
      with MR angiography and/or angiography at 6 months and at 1 year. RESULTS: Of the
      80 patients, 42 (52.5%) did well (Glasgow Outcome Scale score of 1 or 2) (62% of
      the 56 patients with grade IV and 25% of the 24 patients with grade V aneurysms),
      seven (8.75%) presented with poor neurologic status (Glasgow Outcome Scale score
      of 3), and 30 (37.5%) died during the first 6 months (26.7% of the patients with
      grade IV and 62% of the patients with grade V aneurysms). One patient was lost to
      follow-up. The main causes of death were consequences of initial bleeding in the
      patients with grade V aneurysms and vasospasm in the patients with grade IV
      aneurysms. CONCLUSION: The results are at least as encouraging as the outcomes
      reported for the surgical series and suggest that early endovascular treatment of
      high grade hemorrhage is a feasible option, especially because endovascular
      maneuvers can be performed at any time, even during vasospasm.

PMID- 12063224
TI  - Endovascular management of basilar artery aneurysms associated with
      fenestrations.
AB  - BACKGROUND AND PURPOSE: Arterial fenestrations are associated with saccular
      aneurysms that are often difficult to treat with open surgical techniques. We
      evaluated our experience with endovascular treatment of such aneurysms. METHODS:
      Ten consecutive patients with 11 basilar artery aneurysms associated with
      fenestrations were treated with coils by means of the endovascular route between
      November 1994 and February 2000. All patients underwent endovascular embolization
      by the femoral approach, under general anesthesia. Twelve embolization procedures
      were perfomed in the 10 patients. RESULTS: Nine proximal and two distal basilar
      artery fenestration aneurysms were treated successfully. The embolization was
      complete in 10 of the 11 aneurysms. It was incomplete in one case, and complete
      occlusion could not be achieved at the second attempt. There was one regrowth at
      1-year follow-up, which was successfully treated again. Four of the aneurysms
      were treated initially with balloon remodeling, whereas one aneurysm with
      regrowth and one with incomplete occlusion were treated with balloon remodeling
      at the second embolization procedure. In one case, one limb of the fenestration
      was sacrificed. CONCLUSION: Endovascular treatment of basilar artery aneurysms
      associated with fenestrations appears to offer advantages over traditional open
      surgical techniques.

PMID- 12063225
TI  - Selective neck occlusion of a large complex aneurysm of the middle cerebral
      artery trifurcation with the UltraSoft coil.
AB  - We present a case of an unruptured, large, complex, middle cerebral artery
      trifurcation aneurysm that was successfully treated by selective occlusion of the
      neck with a single, newly available UltraSoft coil. The satisfactory initial
      anatomic result was stable, as demonstrated on a 3-month follow-up arteriogram
      that indicated complete anatomic cure. The novel UltraSoft coil offers additional
      possibilities in the endovascular management of difficult-to-treat vascular
      lesions.

PMID- 12063226
TI  - Histopathologic findings in human cerebral aneurysms embolized with platinum
      coils: report of two cases and review of the literature.
AB  - This report describes 2-week and 20-month histopathologic findings in small
      aneurysms embolized with platinum coils. Electron microscopy showed the presence
      of endothelial cells encroaching on the platinum coils at the orifice of the
      aneurysm in both cases. We confirm that endothelial growth can be induced as
      early as 2 weeks after embolization of small human aneurysms with platinum coils,
      similar to previous observations in animal models and human cases.

PMID- 12063227
TI  - Delayed thromboembolic events 9 weeks after endovascular treatment of an anterior
      communicating artery aneurysm: case report.
AB  - We present a case of delayed thromboembolic events that occurred 9 weeks after
      endovascular treatment of an anterior communicating artery aneurysm with GDC.

PMID- 12063228
TI  - Hemostatic closure device after carotid puncture for stent and coil placement in
      an intracranial aneurysm: technical note.
AB  - A 71-year-old female patient presented with a wide-necked carotid cavernous
      aneurysm for which stent and coil placement was planned. Arterial tortuosity
      required direct puncture of the common carotid artery for access. The procedure
      was performed while the patient was receiving antiplatelet and anticoagulative
      therapy. To avoid potentially hazardous and prolonged carotid compression, a
      closure device (Angio-Seal) was used at the end of the procedure. The
      postoperative period was clinically uneventful. Sonographic and angiographic
      follow-up of the carotid artery were performed.

PMID- 12063229
TI  - Risks of tumor embolization in the presence of an unrecognized patent foramen
      ovale: case report.
AB  - A patent foramen ovale (PFO) is a fairly common septal defect in the general
      population. Paradoxical embolization through a PFO is a known cause of stroke.
      Preprocedural recognition of a PFO in a patient undergoing particulate arterial
      embolization can help reduce the risk of cerebral infarction.

PMID- 12063230
TI  - Quantification of brain gray matter damage in different MS phenotypes by use of
      diffusion tensor MR imaging.
AB  - BACKGROUND AND PURPOSE: Increasing evidence exists that cerebral gray matter (GM)
      from patients with multiple sclerosis (MS) is not spared. This study was
      performed to quantify in vivo the extent of cerebral GM pathologic abnormality in
      patients with relapsing-remitting (RR), secondary progressive (SP), and primary
      progressive MS, by using diffusion tensor (DT) MR imaging. METHODS: Dual-echo and
      DT MR imaging of the brain were performed in 102 patients with MS and 30 healthy
      volunteers. After GM segmentation using a technique based on diffusion anisotropy
      thresholding, average diffusivity (D) histograms of the cerebral GM were produced
      for all participants. RESULTS: All D histogram-derived metrics of the GM were
      significantly different between control volunteers and the whole MS population.
      No significant difference was found for any of the D histogram-derived metrics
      between control volunteers and patients with RRMS, whereas significant
      differences were found for D and D histogram peak location between control
      volunteers and patients with PPMS. All the D histogram-derived metrics differed
      significantly between patients with RRMS and patients with SPMS. Patients with
      SPMS also had significantly lower D than did patients with PPMS. All D histogram
      derived metrics of the GM were strongly correlated with the T2 lesion volume.
      CONCLUSIONS: This study confirms the presence of brain GM changes in patients
      with MS. It also shows that the extent of such changes is greater during the
      progressive forms of the disease.

PMID- 12063231
TI  - Serial diffusion-weighted MR imaging and proton MR spectroscopy of acute large
      demyelinating brain lesions: case report.
AB  - We present the serial MR studies of two patients with symptomatic acute large
      demyelinating lesions that initially showed a drop in apparent diffusion
      coefficient values. Baseline proton MR spectroscopy showed a slight decrease in N
      acetylaspartate and a normal choline level. An excess of lactate was observed at
      the first examinations and completely disappeared by the final examinations. The
      time-course evolution of the lesions shown by MR imaging and proton MR
      spectroscopic examinations suggests that the initial drop in apparent coefficient
      diffusion may have been related to dense inflammatory cell infiltration and scant
      tissue destruction or to reversible reduced vascular supply due to the severity
      of the inflammatory process.

PMID- 12063232
TI  - Three-dimensional, T1-weighted gradient-echo imaging of the brain with a
      volumetric interpolated examination.
AB  - BACKGROUND AND PURPOSE: T1-weighted, 3D gradient-echo MR sequences can be
      optimized for rapid acquisition and improved resolution through asymmetric k
      space sampling and interpolation. We compared a volumetric interpolated brain
      examination (VIBE) sequence with a magnetization-prepared rapid acquisition
      gradient echo (MP RAGE) sequence and a 2D T1-weighted spin-echo (SE) sequence.
      METHODS: Thirty consecutive patients known or suspected to have focal brain
      lesions underwent postcontrast studies (20 mL of gadopentetate dimeglumine) with
      VIBE, MP RAGE, and 2D T1-weighted SE imaging. Source and 5-mm VIBE and MP RAGE
      reformations, and 5-mm T1-weighted SE images were compared qualitatively and by
      using signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). SNRs in a
      gadolinium-doped water phantom were also measured for all three sequences.
      RESULTS: On the source images, SNRs for gray matter (GM) and white matter (WM),
      and CNRs for WM-to-GM and contrast-enhancing lesion-to-GM were slightly, but
      significantly higher for the VIBE sequence than for the MP RAGE sequence (P
      <.05). On 5-mm reformations, WM-to-GM CNR was significantly higher on VIBE and MP
      RAGE images than on T1-weighted SE images (P <.001), but contrast-enhancing
      lesion-to-GM CNRs were higher on SE images compared with both gradient-echo
      sequences (P <.001). Qualitatively, VIBE images showed fewer flow artifacts than
      did SE and MP RAGE images (P <.05). In the phantom, VIBE SNR was higher than MP
      RAGE SNR for short T1 relaxation times. CONCLUSION: VIBE provides an effective,
      alternative approach to MP RAGE for fast 3D T1-weighted imaging of the brain.

PMID- 12063233
TI  - Hippocampal shape analysis in status epilepticus associated with acute
      encephalitis.
AB  - We performed MR imaging deformation-based hippocampal shape analysis in a 28-year
      old woman in whom status epilepticus developed after acute encephalitis.
      Hippocampal shape analysis revealed severe global bilateral hippocampal atrophy.
      Regional volume loss was most accentuated in the medial and lateral aspects of
      the hippocampal head; the loss was similar to shape changes in hippocampal
      sclerosis of chronic temporal lobe epilepsy. This deformation pattern may reflect
      a common pathologic process that causes hippocampal volume loss in both of these
      conditions.

PMID- 12063234
TI  - Confounding effect of large vessels on MR perfusion images analyzed with
      independent component analysis.
AB  - BACKGROUND AND PURPOSE: First pass contrast-enhanced MR imaging using gradient
      echo acquisitions is commonly used to assess cerebral blood flow, despite the
      confounding signal from large blood vessels. We hypothesized that removal of this
      unwanted intravascular signal using independent component analysis would result
      in a more accurate depiction of cerebral blood flow. METHODS: Images of 11
      patients, acquired with our acute stroke imaging protocol, were post processed to
      produce images of relative cerebral blood flow (rCBF). The same images were
      processed with independent component analysis to identify and remove the signal
      from large blood vessels, with a second set of rCBF images produced. Both sets of
      rCBF maps were pooled, randomized in order, and read in a blinded fashion by two
      neuroradiologists to assess the level of large artery artifact and overall image
      quality. Significance was determined using a Wilcoxon signed rank test. RESULTS:
      Results from both readers indicated that the level of large artery artifact was
      significantly reduced in the images processed using independent component
      analysis component removal (P <.05). In addition, both readers indicated
      significantly (P <.05) improved image quality of the images processed using
      independent component analysis. CONCLUSION: The removal of the signal resulting
      from large blood vessels before calculation of rCBF resulted in images with
      significantly less artifact and higher image quality.

PMID- 12063235
TI  - Functional CT perfusion imaging in predicting the extent of cerebral infarction
      from a 3-hour middle cerebral arterial occlusion in a primate stroke model.
AB  - BACKGROUND AND PURPOSE: Our purpose was to determine whether cerebral perfusion
      functional CT (fCT), performed after endovascular middle cerebral artery (MCA)
      occlusion, can be used to predict final cerebral infarction extent in a primate
      model. METHODS: fCT with bolus tracking was performed before and 30 and 150
      minutes after 3-hour digital subtraction angiography (DSA)-guided endovascular
      MCA occlusion in five baboons. Parametric cerebral blood flow (CBF), cerebral
      blood volume (CBV) and mean transit time (MTT) maps were constructed by voxel-by
      voxel gamma variate fitting and used to determine lesion sizes. Animals were
      sacrificed 48 hours after the occlusion, and ex vivo MR imaging was performed.
      Lesion sizes on fCT and MR images were compared. RESULTS: Hypoperfusion was
      clearly identified on all images obtained after MCA occlusion. Thirty and 150
      minutes after occlusion onset, respectively, mean lesion sizes were 737 mm(2) +/-
      33 and 737 mm(2) +/- 44 for CBF, 722 mm(2) +/- 32 and 730 mm(2) +/- 43 for CBV,
      and 819 mm(2) +/- 14 and 847 mm(2) +/- 11 for MTT. Mean outcome infarct size on
      MR images was 733 mm(2) +/- 30. Measurements based on CBV and CBF (R(2) = 0.97
      and 0.96, P <.001), but not MTT (R(2) = 0.40, P >.5), were highly correlated with
      final lesion size. CONCLUSION: An endovascular approach to MCA occlusion provides
      a minimally invasive, reproducible animal model for controlled studies of
      cerebral ischemia and infarction. Derived cerebral perfusion maps closely predict
      the 48-hour infarct size after 3-hour MCA occlusion.

PMID- 12063236
TI  - Iron-induced susceptibility effect at the globus pallidus causes underestimation
      of flow and volume on dynamic susceptibility contrast-enhanced MR perfusion
      images.
AB  - BACKGROUND AND PURPOSE: Age-related iron accumulation in extrapyramidal nuclei
      causes T2 shortening, which may result in decreased signal intensity in these
      areas on MR images. Because the dynamic susceptibility contrast-enhanced
      technique uses heavily T2*- or T2-weighted images, the iron-induced
      susceptibility may have direct impact on perfusion imaging. The purpose of this
      study was to assess the effect of iron-induced susceptibility on the calculated
      perfusion parameters. The difference of this effect between gradient-echo and
      spin-echo sequences was also assessed. METHODS: Dynamic susceptibility contrast
      enhanced MR perfusion imaging data of 12 patients were used for this study.
      Perfusion images were obtained using a single shot spin-echo echo-planar imaging
      sequence in seven patients and a gradient-echo echo-planar imaging sequence in
      five patients. Region of interest measurements of relative cerebral blood flow,
      relative cerebral blood volume, and mean transit time were obtained at various
      parts of the gray matter, including the globus pallidus, putamen, caudate
      nucleus, thalamus, and cerebral cortex of temporal, frontal, and occipital lobes.
      The baseline signal intensity on the source images and the magnitude of signal
      change (DeltaR2* or DeltaR2) were also assessed. RESULTS: The globus pallidus had
      statistically significantly lower values of relative cerebral blood flow,
      relative cerebral blood volume, baseline signal intensity, and magnitude of
      signal change compared with other parts of the gray matter for both gradient-echo
      and spin-echo sequences (P <.05). Underestimations of these values were more
      prominent for the gradient-echo than for the spin-echo sequence. Little variance
      in the measured mean transit time was noted. CONCLUSION: Iron-induced
      susceptibility effect may lead to underestimation of relative cerebral blood flow
      and relative cerebral blood volume in the basal ganglia.

PMID- 12063237
TI  - Multiple reproducibility indices for evaluation of cognitive functional MR
      imaging paradigms.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate a variety of
      reproducibility indices for cognitive functional MR imaging (fMRI) paradigms that
      account for both overlapping and extraneous regions of activation. METHODS: Eight
      right-handed volunteers were imaged with fMRI by using a word-generation paradigm
      and a forward-backward text-listening paradigm. The paradigms were performed
      twice in the session and repeated 1 week later. Reproducibility indices for the
      four repeated studies were determined on the basis of pair-wise computation of
      the ratio of the probability-weighted intersection volume divided by the union
      volume of surviving activation clusters. The intersection volume was determined
      by using several iterations of the morphologic dilatation operator with
      additional voxels accrued in the intersection weighted by an exponential
      function. Computed indices included global reproducibility, language area
      reproducibility, extraneous activation reproducibility, and laterality. RESULTS:
      The word-generation paradigm had reproducibility values that were significantly
      greater than those of the forward-backward text-listening paradigm (global
      reproducibility, 0.75 vs 0.5, P <.005; language area reproducibility, 0.85 vs
      0.6, P <.008; mean extraneous activation reproducibility, 0.68 vs 0.41, P <.002).
      The forward-backward text-listening paradigm demonstrated more focal activations,
      whereas the word-generation demonstrated larger activations outside the dominant
      language areas that were highly reproducible. CONCLUSION: For clinically relevant
      language paradigms, multiple reproducibility indices should be taken into account
      in selecting an appropriate paradigm. Compared with a forward-backward text
      listening task, a word-generation task has higher reproducibility indices at the
      expense of localizing ability. The forward-backward paradigm demonstrates more
      focal activations with less extraneous activation.

PMID- 12063238
TI  - Posterior reversible encephalopathy syndrome: prognostic utility of quantitative
      diffusion-weighted MR images.
AB  - BACKGROUND AND PURPOSE: The recently described posterior reversible
      encephalopathy syndrome (PRES) classically consists of reversible vasogenic edema
      in the posterior circulation territories, although conversion to irreversible
      cytotoxic edema has been described. We hypothesized that the extent of edema has
      prognostic implications and that diffusion-weighted MR imaging (DWI) can help
      predict the progression to infarction. METHODS: Twenty-two patients with PRES and
      18 control subjects were examined with isotropic DWI. Nineteen regions of
      interest (ROIs) were systematically placed, and apparent diffusion coefficients
      (ADCs) were computed and correlated with T2 and DWI signal intensity in each ROI.
      RESULTS: T2 signal abnormalities were always present in territories of the
      posterior circulation. Anterior circulation structures were involved in 91% of
      patients. ADC values in areas of abnormal T2 signal were high. More extensive T2
      signal abnormalities were seen in patients with a poor outcome than in patients
      who recovered. In six patients (27%), areas of high DWI signal intensity were
      seen with ADC values that were paradoxically normal, which we called
      pseudonormalized. Abnormal T2 signal intensity and high ADC values surrounded
      these areas. Follow-up images in two patients showed progression to infarction in
      pseudonormalized regions. CONCLUSION: Vasogenic edema in PRES involves
      predominantly the posterior circulation territories, but anterior circulation
      structures are also frequently involved. The extent of combined T2 and DWI signal
      abnormalities correlate with patient outcome. High DWI signal intensity and
      pseudonormalized ADC values are associated with cerebral infarction and may
      represent the earliest sign of nonreversibility as severe vasogenic edema
      progresses to cytotoxic edema.

PMID- 12063239
TI  - Spontaneous regression of cerebral arteriovenous malformation in hereditary
      hemorrhagic telangiectasia.
AB  - Cerebral arteriovenous malformations (AVMs) are associated with hereditary
      hemorrhagic telangiectasia (HHT). I report a case of a patient with HHT with four
      cerebral AVMs in whom one AVM spontaneously regressed during a 5-year period. The
      spontaneous regression of this AVM in this patient with HHT supports the theory
      that AVMs associated with this syndrome have a different natural history than
      that of typical sporadic AVMs.

PMID- 12063240
TI  - Vertebrobasilar transcranial color-coded duplex ultrasonography: improvement with
      echo enhancement.
AB  - BACKGROUND AND PURPOSE: The diagnostic yield of vertebrobasilar transcranial
      color-coded duplex ultrasonography (US) is often hampered by insufficient
      acoustic penetration, anatomic variations, and vessel tortousity. The purpose of
      this study was to evaluate the effect of echo enhancement on vertebrobasilar
      transcranial color-coded duplex US. METHODS: In 23 consecutive patients (mean
      age, 61.0 +/- 11.1 years) with vertebrobasilar stroke, the vertebrobasilar system
      (P1 segment of the posterior cerebral artery [PCA], basilar head, V4 segment of
      the vertebral artery, and basilar artery) was examined with transcranial color
      coded duplex US before and after injection of an echo-enhancer. The acoustic
      window was graded according to visibility of parenchymal structures, and vessel
      imaging was graded according to the appearance of the color mode signal. Maximum
      depth of the basilar color signal was recorded. All patients with an abnormal or
      inconclusive US finding underwent either digital subtraction angiography or MR
      angiography. RESULTS: In the P1 PCA, V4 vertebral artery, basilar artery, and
      basilar head, image quality was insufficient in 65%, 82%, 83%, and 38%,
      respectively, before echo enhancement, and in 15%, 30%, 35%, and 9%,
      respectively, after echo enhancement. In all graded vessels, the improved image
      quality with echo enhancement was statistically significant. Compared with the
      reference examinations in the 15 cases of occlusion or stenosis, definite
      diagnosis was possible in 60% (nine cases) with nonenhanced transcranial color
      coded duplex US and in 93% of (14 cases) after echo enhancement. CONCLUSION: Echo
      enhancement resulted in improved image quality of the vertebrobasilar system and
      markedly increased diagnostic confidence.

PMID- 12063241
TI  - Cranial MR spectroscopy of tetrahydrobiopterin deficiency.
AB  - BACKGROUND AND PURPOSE: Severe and progressive neurologic disease remains a
      problem for patients with hyperphenylalaninemia due to a deficiency of
      tetrahydrobiopterin (BH4), even with early diagnosis and despite treatment with
      BH4 and neurotransmitter precursors. Few reports have included the associated
      imaging characteristics. Our purpose was to describe the imaging features of BH4
      deficient patients identified by neonatal screening in a Taiwanese population and
      to correlate the imaging features with the treatment. METHODS: This study
      analyzed the cases of eight BH4-deficient patients who were examined by MR
      imaging and MR spectroscopy. Analysis of the findings was correlated with the
      clinical findings. RESULTS: One patient whose intelligence quotient score was
      lower than those of the other seven patients experienced seizures in conjunction
      with central white matter signal changes on MR images and a lactate peak on MR
      spectroscopy. Lactate peak was revealed in another patient who had marked
      elevations of N-acetylaspartate:creatine and N-acetylaspartate:choline ratios.
      Although most patients had a higher than average N-acetylaspartate:creatine or N
      acetylaspartate:choline ratio, the patient who had decreases of both ratios
      possessed the highest intelligence quotient scores among the eight patients. In
      addition, the myoinositol:choline ratio correlated positively with the average
      BH4 dosage (P =.027, r = 0.027) and the choline:creatine ratio correlated
      negatively with the average 5-hydroxytryptophan dosage (P =.035, r = -0.742).
      CONCLUSION: Compared with classical phenylketonuria, patients with BH4 deficiency
      have fewer white matter changes revealed by MR imaging but more changes revealed
      by MR spectroscopy. MR spectroscopy is a potential method with which to monitor
      the dosages of supplements used to treat this disorder. In addition, MR
      spectroscopy may be helpful in gaining understanding of the neurophysiological
      changes that occur in association with this disease.

PMID- 12063242
TI  - Ventricular lactate in normal pressure hydrocephalus: from where has it come to
      where does it go?

PMID- 12063243
TI  - Distinct roles for glutathione S-transferases in the oxidative stress response in
      Schizosaccharomyces pombe.
AB  - We have identified three genes, gst1(+), gst2(+), and gst3(+), encoding theta
      class glutathione S-transferases (GSTs) in Schizosaccharomyces pombe. The gst1(+)
      and gst2(+) genes encode closely related proteins (79% identical). Our analysis
      suggests that Gst1, Gst2, and Gst3 all have GST activity with the substrate 1
      chloro-2,4-dinitrobenzene and that Gst3 has glutathione peroxidase activity.
      Although Gst1 and Gst2 have no detectable peroxidase activity, all three gst
      genes are required for normal cellular resistance to peroxides. In contrast, each
      mutant is more resistant to diamide than wild-type cells. The gst1Delta,
      gst2Delta, and gst3Delta mutants are also more sensitive to fluconazole,
      suggesting that GSTs may be involved in anti-fungal drug detoxification. Both
      gst2(+) and gst3(+) mRNA levels increase in stationary phase, and all three gst
      genes are induced by hydrogen peroxide. Indeed, gst1(+), gst2(+), and gst3(+) are
      regulated by the stress-activated protein kinase Sty1. The Gst1 and Gst2 proteins
      are distributed throughout the cell and can form homodimers and Gst1-Gst2
      heterodimers. In contrast, Gst3 is excluded from the nucleus and forms homodimers
      but not complexes with either Gst1 or Gst2. Collectively, our data suggest that
      GSTs have separate and overlapping roles in oxidative stress and drug responses
      in fission yeast.

PMID- 12063244
TI  - Use of biomolecular interaction analysis to elucidate the regulatory mechanism of
      the cysteine synthase complex from Arabidopsis thaliana.
AB  - Real time biomolecular interaction analysis based on surface plasmon resonance
      has been proven useful for studying protein-protein interaction but has not been
      extended so far to investigate enzyme-enzyme interactions, especially as
      pertaining to regulation of metabolic activity. We have applied BIAcore
      technology to study the regulation of enzyme-enzyme interaction during
      mitochondrial cysteine biosynthesis in Arabidopsis thaliana. The association of
      the two enzyme subunits in the hetero-oligomeric cysteine synthase complex was
      investigated with respect to the reaction intermediate and putative effector O
      acetylserine. We have determined an equilibrium dissociation constant of the
      cysteine synthase complex (K(D) = 25 +/- 4 x 10(-9) m), based on a reliable A + B
      <--> AB model of interaction. Analysis of dissociation kinetics in the presence
      of O-acetylserine revealed a half-maximal dissociation rate at 77 +/- 4 microm O
      acetylserine and strong positive cooperativity for complex dissociation. The
      equilibrium of interaction was determined using an enzyme activity-based approach
      and yielded a K(m) value of 58 +/- 7 microm O-acetylserine. Both effector
      concentrations are in the range of intracellular O-acetylserine fluctuations and
      support a functional model that integrates effector-driven cysteine synthase
      complex dissociation as a regulatory switch for the biosynthetic pathway. The
      results show that BIAcore technology can be applied to obtain quantitative
      kinetic data of a hetero-oligomeric protein complex with enzymatic and regulatory
      function.

PMID- 12063245
TI  - Multiple domains of MCIP1 contribute to inhibition of calcineurin activity.
AB  - Calcineurin is a serine/threonine protein phosphatase that plays a critical role
      in many physiologic processes such as T-cell activation, apoptosis, skeletal
      myocyte differentiation, and cardiac hypertrophy. Calcineurin-dependent signals
      are transduced to the nucleus by nuclear factor of activated T-cells (NFAT)
      transcription factors that undergo nuclear translocation upon dephosphorylation
      and promote transcriptional activation of target genes. Several endogenous
      proteins are capable of inhibiting the catalytic activity of calcineurin.
      Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these
      proteins on the basis of its pattern of expression and its function in a negative
      feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be
      phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated
      MCIP1 is a substrate for calcineurin. Peptides corresponding to the substrate
      domain competitively inhibit calcineurin activity in vitro. However, a detailed
      structure/function analysis of MCIP1 reveals that either of two additional
      domains of MCIP1 is sufficient for binding to calcineurin in vitro and for
      inhibition of calcineurin activity in vivo. We conclude that MCIP1 inhibits
      calcineurin through mechanisms that include, but are not limited to, competition
      with other substrates such as nuclear factor of activated T-cells.

PMID- 12063246
TI  - In vivo and in vitro phosphorylation of two isoforms of yeast pyruvate kinase by
      protein kinase A.
AB  - Saccharomyces cerevisiae pyruvate kinase 1 (Pyk1) was demonstrated to be
      associated to an immunoprecipitate of yeast protein kinase A holoenzyme (HA
      Tpk1.Bcy1) and to be phosphorylated in a cAMP-dependent process. Both glutathione
      S-transferase (GST)-Pyk1 and GST-Pyk2 were phosphorylated in vitro by the bovine
      heart protein kinase A (PKA) catalytic subunit and by immobilized yeast HA-Tpk1.
      The specificity constant for the phosphorylation of GST-Pyk1 and GST-Pyk2 by
      bovine catalytic subunit was in the range of the value for Leu-Arg-Arg-Ala-Ser
      Leu-Gly (Kemptide). Both fusion proteins were phosphorylated in vivo, in intact
      cells overexpressing the protein, or in vitro using crude extracts, as source of
      protein kinase A, when a wild type strain was used but were not phosphorylated
      when using a strain with only one TPK gene with an attenuated mutation
      (tpk1(w1)). The effect of phosphorylation on Pyk activity was assayed in
      partially purified preparations from three strains, containing different
      endogenous protein kinase A activity levels. Pyk1 activity was measured at
      different phosphoenolpyruvate concentrations in the absence or in the presence of
      the activator fructose 1,6-bisphosphate at 1.5 mm. Preliminary kinetic results
      derived from the comparison of Pyk1 obtained from extracts with the highest
      versus those from the lowest protein kinase A activity indicate that the enzyme
      is more active upon phosphorylation conditions; in the absence of the activator
      it shows a shift in the titration curve for phosphoenolpyruvate to the left and
      an increase in the Hill coefficient, whereas in the presence of fructose 1,6
      bisphosphate it shows an n(H) value of 1.4, as compared with an n(H) of 2 for the
      Pyk1 obtained from extracts with almost null protein kinase A activity.

PMID- 12063247
TI  - trans-Lesion synthesis past bulky benzo[a]pyrene diol epoxide N2-dG and N6-dA
      lesions catalyzed by DNA bypass polymerases.
AB  - The effectiveness of in vitro primer elongation reactions catalyzed by human
      bypass DNA polymerases kappa (hDinB1), pol eta (hRad30A), pol iota (hRad30B), and
      yeast pol zeta (Rev3 and Rev7) in site-specifically modified template
      oligonucleotide strands were studied in vitro. The templates contained single
      bulky lesions derived from the trans-addition of the mutagenic (+)- or (-)
      enantiomers of r7,t8-dihydroxy-t9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (a
      metabolite of the environmental carcinogen benzo[a]pyrene), to the exocyclic
      amino groups of guanine or adenine in oligonucleotide templates 33, or more,
      bases long. In "running start" primer extension reactions, pol kappa effectively
      bypassed both the stereoisomeric (+)- and (-)-trans-guanine adducts but not the
      analogous adenine adducts. In sharp contrast, pol eta, which exhibits
      considerable sequence homology with pol kappa (both belong to the group of Y
      family polymerases), is partially blocked by the guanine adducts and the (-)
      trans-adenine adduct, although the stereoisomeric (+)-trans-adenine adduct is
      more successfully bypassed. Neither pol iota nor pol zeta, either alone or in
      combination, were effective in trans-lesion synthesis past the same adducts. In
      all cases, the fidelity of insertion is dependent on adduct stereochemistry and
      structure. Generally, error-free nucleotide insertion opposite the lesions tends
      to depend more on adduct stereochemistry than error-prone insertion. None of the
      polymerases tested are a universal bypass polymerase for the stereoisomeric bulky
      polycyclic aromatic hydrocarbon-DNA adducts derived from anti-BPDE.

PMID- 12063248
TI  - Direct interaction between mammalian DNA polymerase beta and proliferating cell
      nuclear antigen.
AB  - Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid
      metabolism as a component of the DNA replication and DNA repair machinery. As
      such, PCNA interacts with many proteins that have a sequence motif termed the
      PCNA interacting motif (PIM) and also with proteins lacking a PIM. Three regions
      in human and rat DNA polymerases beta (beta-pol) that resemble the consensus PIM
      were identified, and we show here that beta-polymerase and PCNA can form a
      complex both in vitro and in vivo. Immunoprecipitation experiments, yeast two
      hybrid analysis, and overlay binding assays were used to examine the interaction
      between the two proteins. Competition experiments with synthetic PIM-containing
      peptides suggested the importance of a PIM in the interaction, and studies of a
      beta-polymerase PIM mutant, H222A/F223A, demonstrated that this alteration
      blocked the interaction with PCNA. The results indicate that at least one of the
      PIM-like sequences in beta-polymerase appears to be a functional PIM and was
      required in the interaction between beta-polymerase and PCNA.

PMID- 12063249
TI  - Biochemical characterization of the chondroitinase B active site.
AB  - Chondroitinase B from Flavobacterium heparinum is the only known lyase that
      cleaves the glycosaminoglycan, dermatan sulfate (DS), as its sole substrate. A
      recent co-crystal structure of chondroitinase B with a disaccharide product of DS
      depolymerization has provided some insight into the location of the active site
      and suggested potential roles of some active site residues in substrate binding
      and catalysis. However, this co-crystal structure was not representative of the
      actual enzyme-substrate complex, because the disaccharide product did not have
      the right length or the chemical structure of the minimal substrate
      (tetrasaccharide) involved in catalysis. Therefore, only a limited picture of the
      functional role of active site residues in DS depolymerization was presented in
      previous structural studies. In this study, by docking a DS tetrasaccharide into
      the proposed active site of the enzyme, we have identified novel roles of
      specific active site amino acids in the catalytic function of chondroitinase B.
      Our conformational analysis also revealed a unique, symmetrical arrangement of
      active site amino acids that may impinge on the catalytic mechanism of action of
      chondroitinase B. The catalytic residues Lys-250, Arg-271, His-272, and Glu-333
      along with the substrate binding residues Arg-363 and Arg-364 were mutated using
      site-directed mutagenesis, and the kinetics and product profile of each mutant
      were compared with recombinant chondroitinase B. Mutating Lys-250 to alanine
      resulted in inactivation of the enzyme, potentially attributable to the role of
      the residue in stabilizing the carbanion intermediate formed during enzymatic
      catalysis. The His-272 and Glu-333 mutants showed diminished enzymatic activity
      that could be indicative of a possible role for one or both residues in the
      abstraction of the C-5 proton from the galactosamine. In addition, the Arg-364
      mutant had an altered product profile after exhaustive digestion of DS,
      suggesting a role for this residue in defining the substrate specificity of
      chondroitinase B.

PMID- 12063250
TI  - A novel phosphatidic acid-selective phospholipase A1 that produces
      lysophosphatidic acid.
AB  - Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological
      properties, although its synthetic pathways have not been completely solved. We
      report the cloning and characterization of a novel phosphatidic acid (PA)
      selective phospholipase A(1) (PLA(1)) that produces 2-acyl-LPA. The PLA(1) was
      identified in the GenBank(TM) data base as a close homologue of
      phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)). When expressed in insect Sf9
      cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did
      not show any catalytic activity toward exogenously added phospholipid substrates.
      However, culture medium obtained from Sf9 cells expressing the enzyme was found
      to activate EDG7/LPA(3), a cellular receptor for 2-acyl-LPA. The activation of
      EDG7 was further enhanced when the cells were treated with phorbol ester or a
      bacterial phospholipase D, suggesting involvement of phospholipase D in the
      process. In the latter condition, an increased level of LPA, but not other
      lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the
      enzyme is observed in several human tissues such as prostate, testis, ovary,
      pancreas, and especially platelets. These data show that the enzyme is a membrane
      associated PA-selective PLA(1) and suggest that it has a role in LPA production.

PMID- 12063251
TI  - Influx of calcium through a redox-sensitive plasma membrane channel in thymocytes
      causes early necrotic cell death induced by the epipolythiodioxopiperazine
      toxins.
AB  - Gliotoxin, a member of the epipolythiodioxopiperazine (ETP) class of toxins,
      induces both apoptotic and necrotic cell death in a concentration-dependent
      manner. Whereas the specific trigger for apoptotic death caused by these toxins
      is unclear, the reactive disulfide bond in the ETP toxins is required for
      biological activity. Thus it is likely that it is the interaction of this
      disulfide moiety with macromolecules in cells that was responsible for activity
      of ETP toxins. Here we present evidence that necrosis induced by gliotoxin and a
      simple synthetic ETP toxin is largely because of an influx of extracellular
      calcium through a redox-sensitive calcium channel in the plasma membrane of
      murine thymocytes. The calcium rises are strongly dependent on the pH of the
      external medium and the presence of external calcium and are abrogated and/or
      reversed by the presence of dithiothreitol, cell impermeant glutathione, and the
      calcium channel blocker Ni(2+). Comparisons with thapsigargin, which indirectly
      causes release of calcium from internal stores, indicates that ETP toxins do not
      provoke calcium rises by store depletion. A mechanism of oxidation by ETP toxins
      of cell surface thiol groups resulting in direct entry of calcium through a redox
      active channel in the plasma membrane is proposed. Necrotic but not apoptotic
      cell death was abrogated by inhibition of calcium entry.

PMID- 12063252
TI  - Phosphatidylinositol 3-kinase/Akt stimulates androgen pathway through GSK3beta
      inhibition and nuclear beta-catenin accumulation.
AB  - PI3K/Akt plays a critical role in prostate cancer cell growth and survival.
      Recent studies have shown that the effect of PI3K/Akt in prostate cells is
      mediated through androgen signaling. The PI3K inhibitor, LY294002, and a tumor
      suppressor, PTEN, negatively regulate the PI3K/Akt pathway and repress AR
      activity. However, the molecular mechanisms whereby PI3K/Akt and PTEN regulate
      the androgen pathway are currently unclear. Here, we demonstrate that blocking
      the PI3K/Akt pathway reduces the expression of an endogenous AR target gene.
      Moreover, we show that the repression of AR activity by LY294002 is mediated
      through phosphorylation and inactivation of GSK3beta, a downstream substrate of
      PI3K/Akt, which results in the nuclear accumulation of beta-catenin. Given the
      recent evidence that beta-catenin acts as a coactivator of AR, our findings
      suggest a novel mechanism by which PI3K/Akt modulates androgen signaling. In a
      PTEN-null prostate cancer cell line, we show that PTEN expression reduces beta
      catenin-mediated augmentation of AR transactivation. Using the mutants of beta
      catenin, we further demonstrate that the repressive effect of PTEN is mediated by
      a GSK3beta-regulated degradation of beta-catenin. Our results delineate a novel
      link among the PI3K, wnt, and androgen pathways and provide fresh insights into
      the mechanisms of prostate tumor development and progression.

PMID- 12063253
TI  - Actinfilin, a brain-specific actin-binding protein in postsynaptic density.
AB  - The dynamic assembly and disassembly of actin-based cytoskeleton is closely
      linked to the changes in the postsynaptic density in both number and shape, which
      is thought to be important in forming long-term memory. Thus, regulation of actin
      filaments may play a critical role in contributing to the formation of long-term
      memory. Here, we report the cloning of actinfilin, a brain-specific Kelch
      protein, which interacts with F-actin. Actinfilin contains an amino-terminal
      POZ/BTB domain and carboxyl positioned six tandem Kelch repeats that presumably
      form six blades of beta-propeller structure of the Kelch domain. Co
      immunoprecipitation analyses showed that the amino-terminal POZ domain mediated
      actinfilin-actinfilin interaction. The recombinant Kelch domain alone was
      sufficient to mediate binding to F-actin. Immunohistochemistry studies of rat
      brain sections suggested that actinfilin is broadly expressed in neurons of most
      regions of the brain. The subcellular localization of actinfilin was studied by
      biochemical fractionation and immunogold labeling. The results showed the
      postsynaptic density distribution of actinfilin. Together, these results indicate
      that actinfilin may be a key player in the actin-based neuronal function.

PMID- 12063254
TI  - Aldose reductase mediates mitogenic signaling in vascular smooth muscle cells.
AB  - Abnormal vascular smooth muscle cell (VSMC) proliferation is a key feature of
      atherosclerosis and restenosis; however, the mechanisms regulating growth remain
      unclear. Herein we show that inhibition of the aldehyde-metabolizing enzyme
      aldose reductase (AR) inhibits NF-kappa B activation during restenosis of balloon
      injured rat carotid arteries as well as VSMC proliferation due to tumor necrosis
      factor alpha (TNF-alpha) stimulation. Inhibition of VSMC growth by AR inhibitors
      was not accompanied by increase in cell death or apoptosis. Inhibition of AR led
      to a decrease in the activity of the transcription factor NF-kappa B in culture
      and in the neointima of rat carotid arteries after balloon injury. Inhibition of
      AR in VSMC also prevented the activation of NF-kappa B by basic fibroblast growth
      factor (bFGF), angiotensin-II (Ang-II), and platelet-derived growth factor (PDGF
      AB). The VSMC treated with AR inhibitors showed decreased nuclear translocation
      of NF-kappa B and diminished phosphorylation and proteolytic degradation of I
      kappa B-alpha. Under identical conditions, treatment with AR inhibitors also
      prevented the activation of protein kinase C (PKC) by TNF-alpha, bFGF, Ang-II,
      and PDGF-AB but not phorbol esters, indicating that AR inhibitors prevent PKC
      stimulation or the availability of its activator but not PKC itself. Treatment
      with antisense AR, which decreased the AR activity by >80%, attenuated PKC
      activation in TNF-alpha, bFGF, Ang-II, and PDGF-AB-stimulated VSMC and prevented
      TNF-alpha-induced proliferation. Collectively, these data suggest that inhibition
      of NF-kappa B may be a significant cause of the antimitogenic effects of AR
      inhibition and that this may be related to disruption of PKC-associated signaling
      in the AR-inhibited cells.

PMID- 12063256
TI  - Inhibition of cell migration and angiogenesis by the amino-terminal fragment of
      24kD basic fibroblast growth factor.
AB  - The 24-kDa form of basic fibroblast growth factor inhibits the migration of
      endothelial cells and mammary carcinoma cells while continuing to promote cell
      proliferation. This molecule consists of the 18-kDa fibroblast growth factor
      sequence plus an additional 55 amino acids at the amino-terminal end. Antibody
      neutralization studies suggested that the inhibition of migration is associated
      with these 55 amino acids, whereas the promotion of proliferation localizes to
      the 18-kDa domain. To determine whether 24kD basic fibroblast growth factor could
      be modified to eliminate its effect on cell proliferation but retain its
      inhibition of migration, portions of the carboxyl-terminal end of 24kD fibroblast
      growth factor were deleted, and the products were tested on MCF-7 and endothelial
      cells. A protein consisting of the 55 amino acids of the amino-terminal end and
      the first 31 amino acids of 18kD basic fibroblast growth factor (ATE+31)
      inhibited migration by 80% but did not promote cell growth. Arginine to alanine
      substitutions within the first 21 amino acids of the carboxyl-terminal end
      substantially reduced the efficacy of ATE+31, whereas substitutions in the
      remaining part of the molecule had no effect. Competition binding experiments
      showed that ATE+31 does not compete with 24kD basic fibroblast growth factor for
      binding to fibroblast growth factor receptor 1. In an in vivo matrigel plug
      assay, 150 nm ATE+31 peptide reduced angiogenesis by 80%. These studies
      demonstrate that the amino-terminal end of 24kD basic fibroblast growth factor is
      responsible for an activity that inhibits the migration rates of cultured cells
      as well as the angiogenic response in vivo.

PMID- 12063255
TI  - Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor
      regulates its coupling to Gs and Gi. Demonstration in a reconstituted system.
AB  - While classically viewed as a prototypic G(s) and adenylyl cyclase-coupled G
      protein-coupled receptor, recent studies have indicated that some aspects of
      beta(2)-adrenergic receptor (beta(2)-AR) signaling are inhibited by pertussis
      toxin, indicating that they are mediated by G(i)/G(o) proteins. These signals
      include activation of ERK MAPKs and Akt activation, as well as hypertrophic and
      anti-apoptotic pathways in cardiac myocytes. Studies in cultured cells have
      suggested the hypothesis that protein kinase A (PKA)-mediated phosphorylation of
      the beta(2)-AR regulates its coupling specificity with respect to G(s) and G(i).
      Using a Chinese hamster ovary cell system, we show that mutant beta(2)-ARs with
      Ala substituted for Ser at consensus PKA sites stimulate robust cyclic AMP
      accumulation (G(s)) but are unable to activate ERK (G(i)). In contrast, Ser -->
      Asp mutants are dramatically impaired in their ability to activate adenylyl
      cyclase but are significantly more active than wild type receptor in activating
      ERK. Activation of adenylyl cyclase by wild type and Ser --> Ala mutant receptors
      is not altered by pertussis toxin, whereas adenylyl cyclase stimulated through
      the Ser --> Asp mutant is enhanced. Activation of ERK by wild type and Ser -->
      Asp receptors is inhibited by pertussis toxin. To further rigorously test the
      hypothesis, we utilized a completely reconstituted system of purified recombinant
      wild type and PKA phosphorylation site mutant beta(2)-ARs and heterotrimeric G(s)
      and G(i). G protein coupling was measured by receptor-mediated stimulation of
      GTPgammaS binding to the G protein. PKA-mediated phosphorylation of the beta(2)
      AR significantly decreased its ability to couple to G(s), while simultaneously
      dramatically increasing its ability to couple to G(i). These results are
      reproduced when a purified recombinant Ser --> Asp mutant beta(2)-AR is tested,
      whereas the Ser --> Ala receptor resembles the unphosphorylated wild type. These
      results provide strong experimental support for the idea that PKA-mediated
      phosphorylation of the beta(2)-adrenergic receptor switches its predominant
      coupling from G(s) to G(i).

PMID- 12063257
TI  - Activation of the beta-catenin/Lef-Tcf pathway is obligate for formation of
      primitive endoderm by mouse F9 totipotent teratocarcinoma cells in response to
      retinoic acid.
AB  - The morphogen retinoic acid promotes the formation of primitive endoderm in mouse
      F9 teratocarcinoma cells as does the stimulation of the Frizzled-1 pathway. We
      investigated whether the beta-catenin/Lef-Tcf-sensitive transcriptional pathway
      activated by Frizzled-1 plays a role in the retinoic acid-induced pathway to
      primitive endoderm formation. An analysis of Lef-Tcf-sensitive transcription
      reveals increased transcription at 1 and 4 h post-treatment with retinoic acid.
      The stimulation of Lef-Tcf-sensitive transcription as well as the formation of
      primitive endoderm was accompanied by the stabilization of beta-catenin as
      observed in activation of the Frizzled-1 pathway. Transient transfection of F9
      cells with an expression vector harboring a dominant-negative mutant of Tcf4
      resulted in the attenuation of both the increase in Lef-Tcf-sensitive
      transcription and formation of primitive endoderm in response to the morphogen.
      Clones stably transfected to express the dominant-negative Tcf4 displayed a block
      in retinoic acid-induced activation of Lef-Tcf-sensitive transcription and
      primitive endoderm formation. These data reveal the obligate role of the beta
      catenin/Lef-Tcf transcriptional pathway in the action of the morphogen retinoic
      acid.

PMID- 12063258
TI  - Importance of FADD signaling in serum deprivation- and hypoxia-induced
      cardiomyocyte apoptosis.
AB  - Although cardiomyocyte (CM) apoptosis has been well described in both in vitro
      and in vivo models of ischemic heart disease, the intracellular pathways leading
      to CM death have not been fully characterized. To define the role of death
      receptor signaling in CM apoptosis, we constructed recombinant adenoviral vectors
      carrying wild-type (wt) or dominant negative (dn) forms of the death receptor
      adaptor protein FADD (Fas-associated death domain protein) and used these vectors
      to transduce rat neonatal CMs in models of hypoxia- and serum deprivation (SD)
      induced apoptosis. The combination of SD and hypoxia induced rapid activation of
      caspase-3 and -8 as well as DNA fragmentation, reaching a plateau within 4-8 h.
      Adenoviral expression of FADD-dn inhibited caspase-8 activation as well as
      hypoxia/SD-induced apoptosis at 24 h in an moi (multiplicity of infection)
      dependent manner. In contrast, adenoviral expression of FADD-wt increased
      apoptosis and caspase-3 activity in CMs under both normoxic and hypoxic
      conditions. Surprisingly, FADD-dn, as well as the specific caspase-8 inhibitor
      benzyloxycarbonyl-IETD-fluoromethylketone also inhibited the activation of
      caspase-9 and -3 in CMs subjected to hypoxia/SD. These data suggest a primary
      role for FADD/caspase-8 signaling that is necessary and sufficient for apoptosis
      of CMs subjected to hypoxia/SD.

PMID- 12063259
TI  - Molecular characterization of an extended binding site for coagulation factor Va
      in the positive exosite of activated protein C.
AB  - The anticoagulant human plasma serine protease, activated protein C (APC),
      inhibits blood coagulation by specific inactivation of the coagulation cofactors
      factor Va (FVa) and factor VIIIa. Site-directed mutagenesis of residues in three
      surface loops of a positive exosite located on APC was used to identify residues
      that play a significant role in binding to FVa. Eighteen different residues were
      mutated to alanine singly, in pairs, or in triple mutation combinations. Mutant
      APC proteins were purified and characterized for their inactivation of FVa. Three
      APC residues were identified that provide major contributions to FVa
      interactions: Lys(193), Arg(229), and Arg(230). In addition, four residues made
      significant minor contributions to FVa interactions: Lys(191), Lys(192),
      Asp(214), and Glu(215). All of these residues primarily contribute to APC
      cleavage at Arg(506) in FVa and play a small role in the interaction of APC with
      the Arg(306) cleavage site. In conjunction with previously published work, these
      results define an extensive FVa binding site in the positive exosite of APC that
      is primarily involved in binding and cleaving at Arg(506) on FVa.

PMID- 12063260
TI  - Structural study of lipomannan and lipoarabinomannan from Mycobacterium chelonae.
      Presence of unusual components with alpha 1,3-mannopyranose side chains.
AB  - Lipomannan (LM) and lipoarabinomannan (LAM) are major glycolipids present in the
      mycobacterial cell wall that are able to modulate the host immune response. In
      this study, we have undertaken the structural determination of these important
      modulins in Mycobacterium chelonae, a fast growing pathogenic mycobacterial
      species. One-dimensional and two-dimensional NMR spectra were used to demonstrate
      that LM and LAM from M. chelonae, designated CheLM and CheLAM, respectively,
      possess structures that differ from the ones reported earlier in other
      mycobacterial species. Analysis by gas chromatography/mass spectrometry of the
      phosphatidyl-myo-inositol anchor, which is thought to play a role in the
      biological functions of these lipoglycans, pointed to a high degree of
      heterogeneity based on numerous combinations of acyl groups on the C-1 and C-2
      positions of the glycerol moiety. Characterization of the mannan core of CheLM
      and CheLAM revealed the presence of novel alpha1,3-mannopyranosyl side chains.
      This motif, which reacted specifically with the lectin from Galanthus nivalis,
      was found to be unique among a panel of nine mycobacterial species. Then, CheLM
      and CheLAM were found to be devoid of both the mannooligosaccharide cap present
      in Mycobacterium tuberculosis and the inositol phosphate cap present in
      Mycobacterium smegmatis and other fast growing species. Tumor necrosis factor
      alpha and interleukin-8 production were assessed from human macrophages with LAM
      preparations from different species. Our results suggest that the inositol
      phosphate capping may represent the major cytokine-inducing component of LAMs.
      This work not only underlines the diversity of LAM structures among various
      mycobacterial species but also provides new structures that could be useful to
      dissect the structure-function relationships of these complex molecules.

PMID- 12063261
TI  - A novel adenine nucleotide translocase inhibitor, MT-21, induces cytochrome c
      release by a mitochondrial permeability transition-independent mechanism.
AB  - The release of cytochrome c from mitochondria is a critical step during
      apoptosis. In order to study this process, we have used a synthetic compound, MT
      21, that is able to initiate release of cytochrome c from isolated mitochondria.
      We demonstrate that MT-21 significantly inhibits ADP transport activity in
      mitochondria and reduces binding of the adenine nucleotide translocase (ANT) to a
      phenylarsine oxide affinity matrix. These results suggest that ANT, one of the
      components of the mitochondrial permeability transition (PT) pore, is the
      molecular target for MT-21. In agreement with this, the MT-21-induced cytochrome
      c release was effectively inhibited in the presence of ANT ligands, and MT-21
      could dissociate ANT from a complex with a glutathione S-transferase-cyclophilin
      D fusion protein. Interestingly, we also found that specific inhibitors of ANT
      such as MT-21 and atractyloside could induce cytochrome c release without
      mitochondrial swelling and that this event was highly dependent on the presence
      of Mg(2+). These results suggest that although ANT resides in the mitochondrial
      inner membrane, specific ANT inhibitors can induce cytochrome c release without
      having an effect on inner membrane permeability. Therefore, MT-21 can be a
      powerful tool for studying the mechanism of PT-independent cytochrome c release
      from mitochondria.

PMID- 12063262
TI  - Nuclear translocation of insulin receptor substrate-1 by the simian virus 40 T
      antigen and the activated type 1 insulin-like growth factor receptor.
AB  - 32D cells are a murine hemopoietic cell line that undergoes apoptosis upon
      withdrawal of interleukin-3 (IL-3) from the medium. 32D cells have low levels of
      the type 1 insulin-like growth factor (IGF-I) receptor and do not express insulin
      receptor substrate-1 (IRS-1) or IRS-2. Ectopic expression of IRS-1 delays
      apoptosis but cannot rescue 32D cells from IL-3 dependence. In 32D/IRS-1 cells,
      IRS-1 is detectable, as expected, in the cytosol/membrane compartment. The SV40
      large T antigen is a nuclear protein that, by itself, also fails to protect 32D
      cells from apoptosis. Co-expression of IRS-1 with the SV40 T antigen in 32D cells
      results in nuclear translocation of IRS-1 and survival after IL-3 withdrawal.
      Expression of a human IGF-I receptor in 32D/IRS-1 cells also results in nuclear
      translocation of IRS-1 and IL-3 independence. The phosphotyrosine-binding domain,
      but not the pleckstrin domain, is necessary for IRS-1 nuclear translocation.
      Nuclear translocation of IRS-1 was confirmed in mouse embryo fibroblasts. These
      results suggest possible new roles for nuclear IRS-1 in IGF-I-mediated growth and
      anti-apoptotic signaling.

PMID- 12063263
TI  - Epidermal growth factor receptor activation under oxidative stress fails to
      promote c-Cbl mediated down-regulation.
AB  - Activation of the epidermal growth factor (EGF) receptor by its ligand, EGF,
      rapidly enhances receptor internalization and degradation, which desensitizes
      receptor signaling. In contrast, we have shown previously that exposure to
      oxidative stress in the form of hydrogen peroxide (H(2)O(2)) activated the EGF
      receptor but that the levels of activated receptors did not decline, which
      resulted in prolonged receptor signaling. This study provides mechanistic
      insights into these different modes of EGF receptor activation. Here we
      demonstrate that the pattern of receptor tyrosine phosphorylation induced by
      H(2)O(2) differs from that induced by its ligand, EGF. Importantly, H(2)O(2)
      generates a receptor with negligible phosphorylation at tyrosine 1045, the major
      docking site for the ubiquitin ligase c-Cbl. As a result, H(2)O(2)-activated
      receptors fail to recruit c-Cbl and do not undergo ubiquitination and
      endocytosis. In summary, H(2)O(2) stimulation results in an activated receptor
      uncoupled from normal down-regulation, a process that may contribute to oxidant
      mediated tumorigenesis.

PMID- 12063264
TI  - Yeast Cox11, a protein essential for cytochrome c oxidase assembly, is a Cu(I)
      binding protein.
AB  - Cox11 is a protein essential for respiratory growth and has been implicated in
      the assembly of the Cu(B) site of cytochrome c oxidase. In the present study, we
      demonstrate that Cox11 is a copper-binding protein. The soluble C-terminal domain
      of Cox11 forms a dimer that coordinates one Cu(I) per monomer via three thiolate
      ligands. The two Cu(I) ions in the dimer exist in a binuclear cluster and appear
      to be ligated by three conserved Cys residues. Mutation of any of these Cys
      residues reduces Cu(I) binding and confers respiratory incompetence. Cytochrome c
      oxidase activity is reduced in these mutants. Thus, the residues important for
      Cu(I) binding correlate with in vivo function, suggesting that Cu(I) binding is
      important in Cox11 function.

PMID- 12063266
TI  - The expression of free oligosaccharides in human seminal plasma.
AB  - Human seminal plasma is a complex mixture of proteins, glycoproteins, peptides,
      glycopeptides, and prostaglandins secreted by organs of the male reproductive
      tract. The components of this fluid have been implicated in the suppression of
      immune response, agonistic effects on sperm-egg binding, and promotion of
      successful implantation of the human embryo. Fractionation followed by
      biophysical analyses revealed that free oligosaccharides constitute a major
      component of the total glycoconjugates within seminal plasma. Significant
      findings of our analyses include the following: (i) the concentration of free
      oligosaccharides is 0.3-0.4 mg/ml; (ii) mono- and difucosylated forms of the
      disaccharide lactose are major components; (iii) many of the remaining
      oligosaccharides are also rich in fucose and carry Lewis(x) and/or Lewis(y)
      epitopes; (iv) a subset of the oligosaccharides express the reducing end sequence
      (GlcNAcbeta1-3/4Glc) not reported in human milk oligosaccharides; (v)
      oligosaccharides in seminal plasma exclusively express type 2 (Galbeta1-4GlcNAc)
      but not the type 1 sequences (Galbeta1-3GlcNAc) that predominate in human milk
      glycans; and (vi) the structural diversity of seminal plasma oligosaccharides is
      far less than human milk oligosaccharides. The agonistic effect of both fucose
      and fucosylated glycoconjugates on human sperm-egg binding in vitro suggests that
      fucosylated oligosaccharides may also promote fertilization in the female
      reproductive tract.

PMID- 12063265
TI  - Participation of the calcium/calmodulin-dependent kinases in hydrogen peroxide
      induced Ikappa B phosphorylation in human T lymphocytes.
AB  - NF-kappaB is an important transcription factor that has a role in a variety of
      responses such as inflammation, oncogenesis, apoptosis, and viral replication.
      Oxidative stress is well known to induce the activation of NF-kappaB. Cells can
      be exposed to either endogenously produced oxidants or oxidants produced by
      surrounding cells. In addition, ischemia reperfusion and certain cancer therapies
      such as chemotherapy and photodynamic therapy are thought to result in oxygen
      radical production. Because of the important role that NF-kappaB has in multiple
      responses, it is critical to determine the mechanisms by which oxidative stress
      induces NF-kappaB activity. We report that the calmodulin antagonist W-7 and the
      calcium/calmodulin-dependent (CaM) kinase inhibitors KN-93 and K252a, can block
      oxidative stress-induced IkappaB phosphorylation in Jurkat T lymphocytes.
      Furthermore, KN-93 but not KN-92 can block hydrogen peroxide-induced Akt and IKK
      phosphorylation. In addition, we found that expression of a kinase-dead CaM-KIV
      construct in two cell lines inhibits IkappaB phosphorylation or degradation and
      that expression of CaM-KIV augments hydrogen peroxide-induced IkappaB
      phosphorylation and degradation. Although the CaM kinases appear to be required
      for this response, increases in intracellular calcium do not appear to be
      required. These results identify the CaM kinases as potential targets that can be
      used to minimize NF-kappaB activation in response to oxidative stress.

PMID- 12063267
TI  - How HIV infection and its treatment affects the cardiovascular system: what is
      known, what is needed.

PMID- 12063268
TI  - Evidence that NOS2 acts as a trigger and mediator of late preconditioning induced
      by acute systemic hypoxia.
AB  - Chronic systemic hypoxia (SH) enhances myocardial ischemic tolerance in mammals.
      We studied the delayed cardioprotection caused by acute SH and associated
      signaling mechanism. Conscious adult male mice were exposed to one or two cycles
      of hypoxia (H; 10% O(2)) or normoxia (21% O(2)) for various durations (30 min, 2
      h, 4 h) followed by 24 h of reoxygenation. Hearts were isolated 24 h later and
      subjected to ischemia-reperfusion in a Langendorff model. Infarct size was
      reduced in mice pretreated with one (H4h) or two cycles (H4hx2) of 4 h SH
      compared with normoxia mice (P < 0.05), which was abolished by an inducible
      nitric oxide synthase (NOS2) inhibitor (S-methylisothiourea, 3 mg/kg) given
      before SH or ischemia. H4hx2 also failed to reduce infarct size in NOS2 knockout
      mice. Cyclooxygenase-2 (COX-2) inhibitor (NS-398, 10 mg/kg) did not block the
      protection given either before H4hx2 or ischemia. A two- to three fold increase
      in myocardial NOS2 expression was observed in H4h, H2hx2, and H4hx2 (P < 0.05),
      whereas endothelial NOS (NOS3) or COX-2 remained unchanged. We conclude that
      acute SH induces delayed cardioprotection, which is triggered and mediated by
      NOS2, but not by NOS3 or COX-2.

PMID- 12063269
TI  - Ketamine abolishes ischemic preconditioning through inhibition of K(ATP) channels
      in rabbit hearts.
AB  - Although ketamine inhibits ATP-sensitive K (K(ATP)) channels in rat ventricular
      myocytes and abolishes the cardioprotective effect of ischemic preconditioning in
      isolated rat hearts and in rabbits in in vivo, no studies to date specifically
      address the precise mechanism of this prevention of ischemic preconditioning by
      ketamine. This study investigated the mechanism of the blockade of ischemic
      preconditioning by ketamine in rabbit ventricular myocytes using patch-clamp
      techniques and in rabbit heart slices model for simulated ischemia and
      preconditioning. In cell-attached and inside-out patches, ketamine inhibited
      sarcolemmal K(ATP) channel activities in a concentration-dependent manner.
      Ketamine decreased the burst duration and increased the interburst duration
      without a change in the single-channel conductance. In the heart slice model of
      preconditioning, heart slices preconditioned with a single 5-min anoxia,
      pinacidil, or diazoxide, followed by 15-min reoxygenation, were protected against
      subsequent 30-min anoxia and 1-h reoxygenation, and the cardioprotection was
      blocked by the concomitant presence of ketamine. These data are consistent with
      the notion that inhibition of sarcolemmal or mitochondrial K(ATP) channels may
      contribute, at least in part, to the mechanism of the blockade of ischemic
      preconditioning by ketamine.

PMID- 12063270
TI  - Myocardial preconditioning factors evoke mesenteric ischemic tolerance via opioid
      receptors and K(ATP) channels.
AB  - We have shown that a reverse-phase concentrate generated from the effluent of
      preconditioned (PC) rabbit hearts evokes a cardioprotective effect in virgin
      acceptor hearts. With the use of a model of sustained (1 h) simulated ischemia in
      isolated, spontaneously contracting rabbit jejunum, our current aims were to 1)
      determine whether protective factor(s) released from PC hearts can improve
      ischemic tolerance in noncardiac tissue; and 2) obtain preliminary insight into
      the mediator(s) involved in triggering and eliciting this remote protection.
      Recovery of contractile force following reoxygenation (our index of ischemic
      tolerance) was enhanced in jejunal segments pretreated with concentrate generated
      from PC hearts (33 +/- 3% of baseline, P < 0.01) versus segments that received no
      concentrate (21 +/- 2%) and segments treated with concentrate from normoxic
      hearts (16 +/- 3%; P < 0.01). Protection achieved with PC concentrate was
      attenuated by coadministration of naloxone or glibenclamide, thereby implicating
      the involvement of opioids and ATP-sensitive potassium channels. Moreover,
      evaluation of purified subfractions of the crude PC concentrate identified a
      specific bioactive fraction that may participate in triggering the improved
      jejunal ischemic tolerance.

PMID- 12063271
TI  - Sites of action of adenosine in interorgan preconditioning of the heart.
AB  - The mechanism underlying interorgan preconditioning of the heart remains elusive,
      although a role for adenosine and activation of a neurogenic pathway has been
      postulated. We tested in rats the hypothesis that adenosine released by the
      remote ischemic organ stimulates local afferent nerves, which leads to activation
      of myocardial adenosine receptors. Preconditioning with a 15-min mesenteric
      artery occlusion (MAO15) reduced infarct size produced by a 60-min coronary
      artery occlusion (60-min CAO) from 68 +/- 2% to 48 +/- 4% (P < 0.05).
      Pretreatment with the ganglion blocker hexamethonium or 8-(p
      sulfophenyl)theophylline (8-SPT) abolished the protection by MAO15.
      Intramesenteric artery (but not intraportal vein) infusion of adenosine (10
      microg/min) was as cardioprotective as MAO15, which was also abolished by
      hexamethonium. Whereas administration of hexamethonium at 5 min of reperfusion
      following MAO15 had no effect, 8-SPT at 5 min of reperfusion abolished the
      protection. Permanent reocclusion of the mesenteric artery before the 60-min CAO
      enhanced the cardioprotection by MAO15 (30 +/- 5%), but all protection was
      abolished when 8-SPT was administered after reocclusion of the mesenteric artery.
      Together, these findings demonstrate the involvement of myocardial adenosine
      receptors. We therefore conclude that locally released adenosine during small
      intestinal ischemia stimulates afferent nerves in the mesenteric bed during early
      reperfusion, initiating a neurogenic pathway that leads to activation of
      myocardial adenosine receptors.

PMID- 12063272
TI  - Adenosine A(1)-receptor induced late preconditioning and myocardial infarction:
      reperfusion duration is critical.
AB  - We investigated the influence of coronary artery reperfusion (CAR) duration on
      the infarct-limiting properties of adenosine A(1)-receptor stimulation-induced
      delayed preconditioning (A(1)-DPC) compared with ischemia-induced delayed
      preconditioning (I-DPC). Sixty-one chronically instrumented conscious rabbits
      successfully underwent the following protocol. On day 1, rabbits were randomly
      divided into four groups: control (saline, iv), I-DPC (six 4-min coronary artery
      occlusion/4-min reperfusion cycles), A(1)-DPC(100) (N(6)-cyclopentyladenosine,
      100 microg/kg iv), and A(1)-DPC(400) (N(6)-cyclopentyladenosine, 400 microg/kg
      iv). On day 2 (i.e., 24 h later), rabbits underwent a 30-min coronary artery
      occlusion after which CAR was started and maintained for either 3 or 72 h.
      Infarct size (percentage of the area at risk) was determined by
      triphenyltetrazolium chloride staining. After 3 h of CAR, I-DPC, A(1)-DPC(100),
      and A(1)-DPC(400) significantly decreased infarct size (36 +/- 5, 41 +/- 4, 38 +/
      5%, respectively) compared with control (55 +/- 3%). After 72 h of CAR, infarct
      sizes were not significantly different among the four groups. This result was
      confirmed by histologic analysis. Thus A(1)-DPC at the two investigated doses, as
      well as I-DPC, decreased infarct size after 3 h but not 72 h of CAR.

PMID- 12063274
TI  - Altered NADH and improved function by anesthetic and ischemic preconditioning in
      guinea pig intact hearts.
AB  - NADH increases during ischemia because O(2) shortage limits NADH oxidation at the
      electron transport chain. Ischemic (IPC) and anesthetic preconditioning (APC)
      attenuate cardiac reperfusion injury. We examined whether IPC and APC similarly
      alter NADH, i.e., mitochondrial metabolism. NADH fluorescence was measured at the
      left ventricular wall of 40 Langendorff-prepared guinea pig hearts. IPC was
      achieved by two 5-min periods of ischemia and APC by exposure to 0.5 or 1.3 mM
      sevoflurane for 15 min, each ending 30 min before 30 min of global ischemia.
      During ischemia, NADH initially increased in nonpreconditioned control hearts and
      then gradually declined below baseline levels. This increase in NADH was lower
      after APC but not after IPC. The subsequent decline was slower after IPC and APC.
      On reperfusion, NADH was less decreased after IPC or APC, mechanical and
      metabolic functions were improved, and infarct size was lower compared with
      controls. Our results indicate that IPC and APC cause distinctive changes in
      mitochondrial metabolism during ischemia and thus lead to improved function and
      tissue viability on reperfusion.

PMID- 12063273
TI  - Anesthetic preconditioning: triggering role of reactive oxygen and nitrogen
      species in isolated hearts.
AB  - We postulated that anesthetic preconditioning (APC) is triggered by reactive
      oxygen/nitrogen species (ROS/RNS). We used the isolated guinea pig heart perfused
      with L-tyrosine, which reacts with ROS and RNS to form strong oxidants,
      principally peroxynitrite (ONOO(-)), and then forms fluorescent dityrosine. ROS
      scavengers superoxide dismutase, catalase, and glutathione (SCG) and NO.
      synthesis inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) were given 5 min
      before and after sevoflurane preconditioning stimuli. Drugs were washed out
      before 30 min of ischemia and 120 min of reperfusion. Groups were control
      (nontreated ischemia control), APC (two, 2-min periods of perfusion with 0.32 +/-
      0.02 mM of sevoflurane; separated by a 6-min period of perfusion without
      sevoflurane), SCG, APC + SCG, L-NAME, and APC + L-NAME. Effluent dityrosine at 1
      min reperfusion was 56 +/- 6 (SE), 15 +/- 5, 40 +/- 5(++), 39 +/- 4(++), 35 +/-
      4(++) , and 33 +/- 5(++) units ((++)P< 0.05 vs. APC), respectively; left
      ventricular pressure (%baseline) at 60 min of reperfusion was 30 +/- 5(++), 60 +/
      4, 35 +/- 5(++), 37 +/- 5(++), 44 +/- 4, and 47 +/- 4; and infarct size (%total
      heart weight) was 50 +/- 5(++), 19 +/- 2, 48 +/- 3(++), 46 +/- 4(++), 42 +/-
      4(++), and 45 +/- 2(++). Thus APC is initiated by ROS as shown by improved
      function, reduced infarct size, and reduced dityrosine on reperfusion; protective
      and ROS/RNS-reducing effect of APC were attenuated when bracketed by ROS
      scavengers or NO* inhibition.

PMID- 12063275
TI  - Delayed cardioprotection by isoflurane: role of K(ATP) channels.
AB  - Isoflurane mimics the cardioprotective effect of acute ischemic preconditioning
      with an acute memory phase. We determined whether isoflurane can induce delayed
      cardioprotection, the involvement of ATP-sensitive potassium (K(ATP)) channels,
      and cellular location of the channels. Neonatal New Zealand White rabbits at 7-10
      days of age (n = 5-16/group) were exposed to 1% isoflurane-100% oxygen for 2 h.
      Hearts exposed 2 h to 100% oxygen served as untreated controls. Twenty-four hours
      later resistance to myocardial ischemia was determined using an isolated perfused
      heart model. Isoflurane significantly reduced infarct size/area at risk (means +/
      SD) by 50% (10 +/- 5%) versus untreated controls (20 +/- 6%). Isoflurane
      increased recovery of preischemic left ventricular developed pressure by 28% (69
      +/- 4%) versus untreated controls (54 +/- 6%). The mitochondrial K(ATP) channel
      blocker 5-hydroxydecanoate (5-HD) completely (55 +/- 3%) and the sarcolemmal
      K(ATP) channel blocker HMR 1098 partially (62 +/- 3%) attenuated the
      cardioprotective effects of isoflurane. The combination of 5-HD and HMR-1098
      completely abolished the cardioprotective effect of isoflurane (56 +/- 5%). We
      conclude that both mitochondrial and sarcolemmal K(ATP) channels contribute to
      isoflurane-induced delayed cardioprotection.

PMID- 12063276
TI  - Nitrate tolerance does not increase production of peroxynitrite in the heart.
AB  - Clinical studies have suggested that long-term nitrate treatment does not improve
      and may even worsen cardiovascular mortality, and the possible role of nitrate
      tolerance has been suspected. Nitrate tolerance has been recently shown to
      increase vascular superoxide and peroxynitrite production leading to vascular
      dysfunction. Nevertheless, nitrates exert direct cardiac effects independent from
      their vascular actions. Therefore, we investigated whether in vivo nitroglycerin
      treatment leading to vascular nitrate tolerance increases cardiac formation of
      nitric oxide (NO), reactive oxygen species, and peroxynitrite, thereby leading to
      cardiac dysfunction. Nitrate tolerance increased bioavailability of NO in the
      heart without increasing formation of reactive oxygen species. Despite elevated
      myocardial NO, neither cardiac markers of peroxynitrite formation nor cardiac
      mechanical function were affected by nitroglycerin treatment. However, serum free
      nitrotyrosine, a marker for systemic peroxynitrite formation, was significantly
      elevated in nitroglycerin-treated animals. This is the first demonstration that,
      although the systemic effects of nitroglycerin may be deleterious due to
      enhancement of extracardiac peroxynitrite formation, nitroglycerin does not
      result in oxidative damage in the heart.

PMID- 12063277
TI  - Role of glycosylation in cell surface expression and stability of HERG potassium
      channels.
AB  - The human ether-a-go-go-related gene (HERG) encodes the pore-forming subunit of
      the rapidly activating delayed rectifier potassium channel in the heart. We
      previously showed that HERG channel protein is modified by N-linked
      glycosylation. HERG protein sequence contains two extracellular consensus sites
      for N-linked glycosylation (N598, N629). In this study, we used the approaches of
      site-directed mutagenesis and biochemical modification to inhibit N-linked
      glycosylation and studied the role of glycosylation in the cell surface
      expression and turnover of HERG channels. Our results show that N598 is the only
      site for N-linked glycosylation and that glycosylation is not required for the
      cell surface expression of functional HERG channels. In contrast, N629 is not
      used for glycosylation, but mutation of this site (N629Q) causes a protein
      trafficking defect, which results in its intracellular retention. Pulse-chase
      experiments show that the turnover rate of nonglycosylated HERG channel is faster
      than that of the glycosylated form, suggesting that N-linked glycosylation plays
      an important role in HERG channel stability.

PMID- 12063278
TI  - Mutation of COOH-terminal lysines in overexpressed alpha B-crystallin abrogates
      ischemic protection in cardiomyocytes.
AB  - High levels of alpha B-crystallin are present in the cardiomyocyte, yet little is
      understood about the function and importance of this protein. Like many other
      small heat shock proteins, alpha B-crystallin forms large oligomeric complexes
      whose size can be regulated by posttranslational modifications. The size of these
      complexes can modify the function of the protein. A naturally occurring COOH
      terminal mutant has many detrimental effects in the lens of the eye and altered
      oligomerization. Therefore, we mutated the two COOH-terminal lysines of alpha B
      crystallin to glycines (K174/175G) and adenovirally mounted them to transduce
      cardiomyocytes. We analyzed the effect of this mutation on oligomerization,
      microtubular stabilization, and ischemic outcome. A nearly 45% downward shift in
      complex size was observed with the mutant by native PAGE followed by
      immunoblotting. The overexpressed protein no longer protected the tubulin
      cytoskeleton against ischemic stress by confocal analysis. The mutant caused a
      30% increase in cytosolic enzyme release with ischemia compared with control,
      whereas a 33% decrease was associated with wild-type alpha B-crystallin
      overexpression. We conclude that the COOH terminus of alpha B-crystallin is
      crucial to its proper function.

PMID- 12063279
TI  - Increasing P(50) does not improve DO(2CRIT) or systemic VO(2) in severe anemia.
AB  - Reducing the hemolobin (Hb)-O(2) binding affinity facilitates O(2) unloading from
      Hb, potentially increasing tissue mitochondrial O(2) availability. We
      hypothesized that a reduction of Hb-O(2) affinity would increase O(2) extraction
      when tissues are O(2) supply dependent, reducing the threshold of critical O(2)
      delivery (DO(2 CRIT)). We investigated the effects of increased O(2) tension at
      which Hb is 50% saturated (P(50)) on systemic O(2) uptake (VO(2) (SYS)), DO(2
      CRIT), lactate production, and acid-base balance during isovolemic hemodilution
      in conscious rats. After infusion of RSR13, an allosteric modifier of Hb, P(50)
      increased from 36.6 +/- 0.3 to 48.3 +/- 0.6 but remained unchanged at 35.4 +/-
      0.8 mmHg after saline (control, CON). Arterial O(2) saturations were equivalent
      between RSR13 and saline groups, but venous PO(2) was higher and venous O(2)
      saturation was lower after RSR13. Convective O(2) delivery progressively declined
      during hemodilution reaching the DO(2 CRIT) at 3.4 +/- 0.8 ml x min(-1) x 100 g(
      1) (CON) and 3.6 +/- 0.6 ml x min(-1) x 100 g(-1) (RSR13). At Hb of 8.1 g/l VO(2)
      (SYS) started to decrease (CON: 1.9 +/- 0.1; RSR13: 1.8 +/- 0.2 ml x min(-1) x
      100 g(-1)) and fell to 0.8 +/- 0.2 (CON) and 0.7 +/- 0.2 ml x min(-1). 100 g(-1)
      (RSR13). Arterial lactate was lower in RSR13-treated than in control animals when
      animals were O(2) supply dependent. The decrease in base excess, arterial pH, and
      bicarbonate during O(2) supply dependence was significantly less after RSR13 than
      after saline. These findings demonstrate that during O(2) supply dependence
      caused by severe anemia, reducing Hb-O(2) binding affinity does not affect VO(2)
      (SYS) or DO(2 CRIT) but appears to have beneficial effects on oxidative
      metabolism and acid base balance.

PMID- 12063280
TI  - Conduction of hyperpolarization along hamster feed arteries: augmentation by
      acetylcholine.
AB  - The conduction of vasodilation along resistance vessels has been presumed to
      reflect the electrotonic spread of hyperpolarization from cell to cell along the
      vessel wall through gap junction channels. However, the vasomotor response to
      acetylcholine (ACh) encompasses greater distances than can be explained by
      passive decay. To investigate the underlying mechanism for this behavior, we
      tested the hypothesis that ACh augments the conduction of hyperpolarization. Feed
      arteries (n = 23; diameter, 58 +/- 4 microm; segment length, 2-8 mm) were
      isolated from the hamster retractor muscle, cannulated at each end, and
      pressurized to 75 mmHg (at 37 degrees C). Vessels were impaled with one or two
      dye-containing microelectrodes simultaneously (separation distance, 50 microm to
      3.5 mm). Membrane potential (E(m)) (rest, approximately -30 mV) and electrical
      responses were similar between endothelium and smooth muscle, as predicted for
      robust myoendothelial coupling. Current injection (-0.8 nA, 1.5 s) evoked
      hyperpolarization (-10 +/- 1 mV; membrane time constant, 240 ms) that conducted
      along the vessel with a length constant (lambda) = 1.2 +/- 0.1 mm; spontaneous
      E(m) oscillations (approximately 1 Hz) decayed with lambda = 1.2 + 0.1 mm. In
      contrast, ACh microiontophoresis (500 nA, 500 ms, 1 microm tip) evoked
      hyperpolarization (-14 +/- 2 mV) that conducted with lambda = 1.9 +/- 0.1 mm, 60%
      further (P < 0.05) than responses evoked by purely electrical stimuli. These
      findings indicate that ACh augments the conduction of hyperpolarization along the
      vessel wall.

PMID- 12063282
TI  - Myogenic response of rat femoral small arteries in relation to wall structure and
      [Ca(2+)](i).
AB  - The present study investigated the influence of media thickness on myogenic tone
      and intracellular calcium concentration ([Ca(2+)](i)) in rat skeletal muscle
      small arteries. A ligature was loosely tied around one external iliac artery of 5
      wk-old spontaneously hypertensive rats. At 18 wk of age, femoral artery blood
      pressure was 102 +/- 11 mmHg (n = 15) on the ligated side and 164 +/- 6 mmHg (n =
      15) on the contralateral side. Small arteries feeding the gracilis muscle had a
      reduced media cross-sectional area and a reduced media-to-lumen ratio on the
      ligated side, where also the range of myogenic constriction was shifted to lower
      pressures. However, when expressed as a function of wall stress, diameter
      responses were nearly identical. [Ca(2+)](i) was higher in vessels from the
      ligated hindlimb at pressures above 10 mmHg, but vasoconstriction was not
      accompanied by changes in [Ca(2+)](i). Thus the myogenic constriction here seems
      due primarily to changes in intracellular calcium sensitivity, which are
      determined mainly by the force per cross-sectional area of the wall and therefore
      altered by changes in vascular structure.

PMID- 12063281
TI  - Effects of oxygen tension on energetics of cultured vascular smooth muscle.
AB  - Chronic hypoxia is a clinically important condition known to cause vascular
      abnormalities. To investigate the cellular mechanisms involved, we kept rings of
      a rat tail artery for 4 days in hypoxic culture (HC) or normoxic culture (NC)
      (PO(2) = 14 vs. 110 mmHg) and then measured contractility, oxygen consumption
      (JO(2)), and lactate production (J(lac)) in oxygenated medium. Compared with
      fresh rings, basal ATP turnover (J(ATP)) was decreased in HC, but not in NC, with
      a shift from oxidative toward glycolytic metabolism. JO(2) during mitochondrial
      uncoupling was reduced by HC but not by NC. Glycogen stores were increased 40
      fold by HC and fourfold by NC. Maximum tension in response to norepinephrine and
      the JO(2) versus tension relationship (JO(2) vs. high K(+) elicited force) were
      unaffected by either HC or NC. Force transients in response to caffeine were
      increased in HC, whereas intracellular Ca(2+) wave activity during adrenergic
      stimulation was decreased. Protein synthesis rate was reduced by HC. The results
      show that long-term hypoxia depresses basal energy turnover, impairs
      mitochondrial capacity, and alters Ca(2+) homeostasis, but does not affect
      contractile energetics. These alterations may form a basis for vascular damage by
      chronic hypoxia.

PMID- 12063284
TI  - Characterization of the normal cardiac myofiber field in goat measured with MR
      diffusion tensor imaging.
AB  - Cardiac myofiber orientation is a crucial determinant of the distribution of
      myocardial wall stress. Myofiber orientation is commonly quantified by helix and
      transverse angles. Accuracy of reported helix angles is limited. Reported
      transverse angle data are incomplete. We measured cardiac myofiber orientation
      postmortem in five healthy goat hearts using magnetic resonance-diffusion tensor
      imaging. A novel local wall-bound coordinate system was derived from the
      characteristics of the fiber field. The transmural course of the helix angle
      corresponded to data reported in literature. The mean midwall transverse angle
      ranged from -12 +/- 4 degrees near the apex to +9.0 +/- 4 degrees near the base
      of the left ventricle, which is in agreement with the course predicted by Rijcken
      et al. (18) using a uniform load hypothesis. The divergence of the myofiber field
      was computed, which is a measure for the extent to which wall stress is
      transmitted through the myofiber alone. It appeared to be <0.07 mm(-1) throughout
      the myocardial walls except for the fusion sites between the left and right
      ventricles and the insertion sites of the papillary muscles.

PMID- 12063283
TI  - Expression and coassociation of ERG1, KCNQ1, and KCNE1 potassium channel proteins
      in horse heart.
AB  - In dogs and in humans, potassium channels formed by ether-a-go-go-related gene 1
      protein ERG1 (KCNH2) and KCNQ1 alpha-subunits, in association with KCNE beta
      subunits, play a role in normal repolarization and may contribute to abnormal
      repolarization associated with long QT syndrome (LQTS). The molecular basis of
      repolarization in horse heart is unknown, although horses exhibit common cardiac
      arrhythmias and may receive drugs that induce LQTS. In horse heart, we have used
      immunoblotting and immunostaining to demonstrate the expression of ERG1, KCNQ1,
      KCNE1, and KCNE3 proteins and RT-PCR to detect KCNE2 message. Peptide N
      glycosidase F-sensitive forms of horse ERG1 (145 kDa) and KCNQ1 (75 kDa) were
      detected. Both ERG1 and KCNQ1 coimmunoprecipitated with KCNE1. Cardiac action
      potential duration was prolonged by antagonists of either ERG1 (MK-499,
      cisapride) or KCNQ1/KCNE1 (chromanol 293B). Patch-clamp analysis confirmed the
      presence of a slow delayed rectifier current. These data suggest that
      repolarizing currents in horses are similar to those of other species, and that
      horses are therefore at risk for acquired LQTS. The data also provide unique
      evidence for coassociation between ERG1 and KCNE1 in cardiac tissue.

PMID- 12063285
TI  - Impaired collateral development in mature rats.
AB  - The effect of maturation on collateral development of resistance arteries was
      investigated. Three to four sequential mesenteric arteries were ligated to create
      collateral pathways in anesthetized young (approximately 200 g) and mature
      (approximately 600 g) rats. Blood flow was similarly elevated in collaterals of
      young and mature animals. In vivo inner arterial diameter was increased only
      within young collaterals (33 +/- 7%, P < 0.001). Increases in number of intimal
      nuclei (57 +/- 10% vs. 52 +/- 14%) and cross-sectional medial area (33 +/- 13%
      vs. 38 +/- 5%) were similar between young and mature collaterals. Relative to the
      same animal controls, collateral endothelial nitric oxide synthase mRNA was
      increased as much in mature as in young rats. Proteomic analysis revealed
      significant differences in protein expression with maturation between control
      arteries as well as flow-loaded collateral vessels. The results indicate that,
      whereas intimal and medial remodeling events were similar in collaterals of young
      and mature rats, luminal expansion occurred only in young rats. Alteration in
      arterial protein expression with maturation and altered responses to stimuli for
      collateral development may contribute to this impairment.

PMID- 12063286
TI  - Scar and pulmonary expression and shedding of ACE in rat myocardial infarction.
AB  - We examined the topology of angiotensin-converting enzyme (ACE) mRNA expression,
      activity, and shedding in myocardial infarction-induced heart failure and sought
      to elucidate the source of the increased plasma ACE activity in this model. Three
      months after coronary ligature, lung, scar, and remaining viable left ventricular
      tissues were analyzed for ACE mRNA expression as well as tissue and solubilized
      ACE activity. ACE mRNA expression increased in the scar with respect to infarct
      severity, decreased in the lung, and remained unchanged in the left ventricle.
      ACE activity decreased in the lung and increased in the scar tissue and plasma.
      Shedding of ACE remained constant in the lung and increased in the scar. This
      study shows that ACE expression and activity is shifted from the pulmonary
      endothelium to the infarct scar tissue and that constancy of shedding in the lung
      and its increase in the scar are the source of the increased plasma ACE in
      congestive heart failure.

PMID- 12063287
TI  - Moderate alcohol consumption induces sustained cardiac protection by activating
      PKC-epsilon and Akt.
AB  - C57BL/6 mice were fed 18% ethanol (vol/vol) in drinking water for 12 wk.
      Isovolumic hearts were subjected to 20 min of ischemia and 30 min of reperfusion
      on a Langendorff apparatus. There were no differences in baseline hemodynamic
      function between hearts from ethanol (EtOH)-fed mice and controls. However, prior
      alcohol consumption doubled recovery of left ventricular developed pressure (68
      +/- 8 vs. 33 +/- 8 mmHg for controls; n = 10, P < 0.05) and reduced creatine
      kinase release by half (0.26 +/- 0.04 vs. 0.51 +/- 0.08 U x min(-1) x g wet wt(
      1) for controls; n = 10, P < 0.05). EtOH feeding doubled expression of activated
      protein kinase C epsilon (PKC)epsilon (n = 6, P < 0.05); whereas PKC inhibition
      blocked protection during ischemia-reperfusion. EtOH feeding also increased
      expression of Akt three- to fivefold (n = 6, P < 0.05), whereas PKC inhibition
      prevented increases in Akt kinase activity. We conclude that signaling pathways
      involving PKC-epsilon are critical for sustained EtOH-mediated cardioprotection
      and that Akt may be a downstream effector of resistance to myocardial reperfusion
      injury.

PMID- 12063289
TI  - Expression of TASK-1, a pH-sensitive twin-pore domain K(+) channel, in rat
      myocytes.
AB  - We have investigated the expression of TASK-1, a pH-sensitive, twin-pore domain
      K(+) channel in the rat heart. A mammalian cell line of Chinese hamster ovary
      cells (CHO), transfected with a plasmid containing mouse TASK-1, demonstrated the
      specificity of the anti-TASK-1 antibody. TASK-1 expression in cardiac tissue was
      initially demonstrated by Western blot and then localized by immunofluorescence.
      In single rat ventricular myocytes, strong staining of the TASK-1 protein was
      located at the intercalated disks and across the cell in a striated pattern,
      corresponding to the transverse axial tubular network (T tubules). In contrast,
      single rat atrial myocytes were stained at the intercalated disks with a weak
      punctate, striated pattern corresponding to underdeveloped T tubules. Also,
      formamide was used to induce the detubulation of ventricular myocytes, which
      enabled confirmation that TASK-1 protein expression occurs in T tubules.
      Consistent with this, RT-PCR revealed the expression of TASK-1 mRNA in total RNA
      from both the ventricles and atria. In this study, we conclusively demonstrated
      that TASK-1 protein and mRNA were expressed in rat atrial and ventricular tissue.
      The extensive distribution of TASK-1 shown to exist within myocyte membranes may
      provide a potential future target for antiarrhythmic drugs.

PMID- 12063288
TI  - Interleukin-11 attenuates human vascular smooth muscle cell proliferation.
AB  - Interleukin (IL)-11 is a growth factor for megakaryocytes, osteoclasts, and
      intestinal mucosa. IL-11 is also an anti-inflammatory agent, mediating many of
      its effects by inhibition of the transcriptional activator nuclear factor (NF)
      kappa B. The purposes of this study were to examine the effects of IL-11 on human
      vascular smooth muscle cell (VSMC) proliferation and NF-kappa B activity. VSMC
      were cultured from human transplant donor aortas, stimulated with basic
      fibroblastic growth factor (bFGF), and treated with IL-11. VSMC stimulated with
      bFGF demonstrated an increase in cell number by direct cell counting and
      mitochondrial activity. IL-11 caused a concentration-dependent decrease in bFGF
      induced VSMC proliferation. Furthermore, IL-11 attenuated bFGF-induced increases
      in cytoplasmic and intranuclear unbound NF-kappa B p65. Similarly, IL-11
      attenuated VSMC expression of two NF-kappa B-dependent cytokines, IL-8 and IL-6.
      Stimulated VSMC did not secrete IL-11, suggesting that endogenous IL-11 did not
      account for our observations. In conclusion, IL-11 inhibits human VSMC
      proliferation in vitro and is associated with suppression of NF-kappa B.

PMID- 12063290
TI  - Nutritive blood flow improves interstitial glucose and lactate exchange in
      perfused rat hindlimb.
AB  - Microdialysis was used to assess the interstitial concentrations of glucose and
      lactate in the constant-flow-perfused rat hindlimb under varying levels of
      nutritive flow controlled by vasoconstrictors. Increased nutritive flow was
      achieved by norepinephrine (NE) or angiotensin II (ANG II) and decreased
      nutritive flow by serotonin (5-HT). NE and ANG II increased oxygen and glucose
      uptake as well as hindlimb lactate release by 50%. 5-HT decreased oxygen uptake
      by 15% but had no significant effect on glucose uptake or hindlimb lactate
      release. Microdialysis recovery of glucose and lactate was significantly elevated
      by NE and ANG II and decreased by 5-HT. The calculated interstitial concentration
      of glucose was increased by NE and ANG II but decreased by 5-HT. The interstitial
      concentration of lactate was decreased by NE and ANG II but increased by 5-HT. In
      all cases, nitroprusside reversed the effects of the vasoconstrictors. These data
      indicate that increased nutritive blood flow enhances the exchange of glucose and
      lactate by improving the supply of glucose to and the removal of lactate from the
      interstitium.

PMID- 12063291
TI  - CaMKII-dependent reactivation of SR Ca(2+) uptake and contractile recovery during
      intracellular acidosis.
AB  - In hearts, intracellular acidosis disturbs contractile performance by decreasing
      myofibrillar Ca(2+) response, but contraction recovers at prolonged acidosis. We
      examined the mechanism and physiological implication of the contractile recovery
      during acidosis in rat ventricular myocytes. During the initial 4 min of
      acidosis, the twitch cell shortening decreased from 2.3 +/- 0.3% of diastolic
      length to 0.2 +/- 0.1% (means +/- SE, P < 0.05, n = 14), but in nine of these
      cells, contractile function spontaneously recovered to 1.5 +/- 0.3% at 10 min (P
      < 0.05 vs. that at 4 min). During the depression phase, both the diastolic
      intracellular Ca(2+) concentration ([Ca(2+)](i)) and Ca(2+) transient (CaT)
      amplitude increased, and the twitch [Ca(2+)](i) decline prolonged significantly
      (P < 0.05). In the cells that recovered, a further increase in CaT amplitude and
      a reacceleration of twitch [Ca(2+)](i) decline were observed. The increase in
      diastolic [Ca(2+)](i) was less extensive than the increase in the cells that did
      not recover (n = 5). Blockade of sarcoplasmic reticulum (SR) function by
      ryanodine (10 microM) and thapsigargin (1 microM) or a selective inhibitor of
      Ca(2+)-calmodulin kinase II, 2-[N- (2-hydroxyethyl)-N-(4-methoxybenzenesulfonyl)]
      amino-N-(4-chlorocinnamyl)-N-methyl benzylamine (1 microM) completely abolished
      the reacceleration of twitch [Ca(2+)](i) decline and almost eliminated the
      contractile recovery. We concluded that during prolonged acidosis, Ca(2+)
      calmodulin kinase II-dependent reactivation of SR Ca(2+) uptake could increase SR
      Ca(2+) content and CaT amplitude. This recovery can compensate for the decreased
      myofibrillar Ca(2+) response, but may also cause Ca(2+) overload after returning
      to physiological pH(i).

PMID- 12063292
TI  - Differences in E2F subunit expression in quiescent and proliferating vascular
      smooth muscle cells.
AB  - E2F is a family of transcriptional factors that control G(1)/S transition. We
      investigated how the E2F family participates in the biological responses of
      vascular smooth muscle cells (VSMC) to vasoconstrictive hormones compared with
      fetal bovine serum (FBS). FBS induced upregulation of E2F-1 and E2F-5 at both
      mRNA and protein levels and slightly reduced E2F-3 protein. Angiotensin II (ANG
      II) and arginine vasopressin increased E2F-3 protein, but not E2F-1 and E2F-5,
      without upregulating its mRNA level. FBS transactivated the E2F-1 gene through
      the induction of free E2F-1 binding onto its promoter, whereas ANG II-induced
      binding of E2F-3 did not result in activation of the E2F-1 promoter. These
      changes are responsible for hypertrophic or hyperplastic response of VSMC to
      different growth factors or stimulants. In contrast, both FBS and
      vasoconstrictive hormones drove transcription of the cdc6 gene by downregulating
      p130 and recruiting free E2F-3 in the latter, which underlies the progression of
      VSMC into S phase.

PMID- 12063293
TI  - Role of USF1 phosphorylation on cardiac alpha-myosin heavy chain promoter
      activity.
AB  - Contractile activity of the cardiac myocyte is required for maintaining cell mass
      and phenotype, including expression of the cardiac-specific alpha-myosin heavy
      chain (alpha-MHC) gene. An E-box hemodynamic response element (HME) located at
      position -47 within the alpha-MHC promoter is both necessary and sufficient to
      confer contractile responsiveness to the gene and has been shown to bind upstream
      stimulatory factor-1 (USF1). When studied in spontaneously contracting cardiac
      myocytes, there is enhanced binding of USF1 to the HME compared with quiescent
      cells, which correlates with a threefold increase in alpha-MHC promoter activity.
      A molecular mechanism by which contractile function modulates alpha-MHC
      transcriptional activity may involve signaling via phosphorylation of USF1. The
      present studies showed that purified rat USF1 was phosphorylated in vitro by
      protein kinase C (PKC) and cAMP-dependent protein kinase (PKA) but not casein
      kinase II. Phosphorylated USF1 by either PKC or PKA had increased DNA binding
      activity to the HME. PKC-mediated phosphorylation also leads to the formation of
      USF1 multimers as assessed by gel shift assay. Analysis of in vivo phosphorylated
      nuclear proteins from cultured ventricular myocytes showed that USF1 was
      phosphorylated, and resolution by two-dimensional gel electrophoresis identified
      at least two distinct phosphorylated USF1 molecules. These results suggest that
      endogenous kinases can covalently modify USF1 and provide a potential molecular
      mechanism by which the contractile stimulus mediates changes in myocyte gene
      transcription.

PMID- 12063294
TI  - Ovariectomy upregulates expression of estrogen receptors, NOS, and HSPs in
      porcine platelets.
AB  - Platelets participate in normal and pathological thrombotic processes. Hormone
      replacement in postmenopausal women is associated with increase risk for
      thrombosis. However, little is known regarding how platelets are affected by
      hormonal status. Nitric oxide (NO) modulates platelet functions and is modulated
      by hormones. Therefore, the present study was designed to determine how loss of
      ovarian hormones changes expression of estrogen receptors and regulatory proteins
      for NO synthase (NOS) in platelets. Estrogen receptors (ER alpha and ER beta),
      NOS, heat shock proteins 70 and 90 (HSP70 and HSP90), caveolin-1, -2, and -3,
      calmodulin, NOS activity, and cGMP were analyzed in a lysate of platelets from
      gonadally intact and ovariectomized female pigs. Expression of ER beta and ER
      alpha receptors, endothelial NOS (eNOS), HSP70, and HSP90 increased with
      ovariectomy. NOS activity and cGMP also increased; calmodulin was unchanged.
      Caveolins were not detected. These results suggest that ovarian hormones
      influence expression of estrogen receptors and eNOS in platelets. Changes in
      estrogen receptors and NOS could affect platelet aggregation in response to
      hormone replacement.

PMID- 12063295
TI  - Expression of kinin B(1) receptor in fresh or cultured rabbit aortic smooth
      muscle: role of NF-kappa B.
AB  - Kinin B(1) receptor (B(1)R) expression and the importance of the transcription
      factor nuclear factor (NF)-kappa B in this process were evaluated in models based
      on the rabbit aorta: freshly isolated tissue (postisolation induction) and
      cultured smooth muscle cells (SMCs). A 3-h incubation of freshly isolated tissues
      determined a sharp B(1)R mRNA increase (RT-PCR). Coincubation of tissues with a
      stimulus (interleukin-1 beta, fetal bovine serum, epidermal growth factor, or
      cycloheximide) further increased mRNA levels. Cultured SMCs possessed a basal
      population of surface B(1)Rs ([(3)H]Lys-des-Arg(9)-bradykinin binding) that was
      upregulated by treatments with the same set of stimuli (binding, mRNA, nuclear
      runon). Pharmacological inhibitors of NF-kappa B (MG-132, BAY 11-7082,
      dexamethasone) or actinomycin D reduced the postisolation induction of B(1)Rs in
      fresh aortic tissue (contractility or mRNA) and the cytokine effect on cells
      (mRNA, binding). NF-kappa B may be a common mediator of various stimuli that
      increase B(1)R gene transcription in the rabbit aorta, including tissue
      isolation, but cycloheximide also stabilizes B(1)R mRNA. The SMC models
      faithfully mimic the in vivo situation with regard to B(1)R regulation.

PMID- 12063296
TI  - Cortisol-mediated potentiation of uterine artery contractility: effect of
      pregnancy.
AB  - During pregnancy, maternal plasma cortisol concentrations approximately double.
      Given that cortisol plays an important role in the regulation of vascular
      reactivity, the present study investigated the potential role of cortisol in
      potentiation of uterine artery (UA) contractility and tested the hypothesis that
      pregnancy downregulated the cortisol-mediated potentiation. In vitro cortisol
      treatment (3, 10, or 30 ng/ml for 24 h) produced a dose-dependent increase in
      norepinephrine (NE)-induced contractions in both nonpregnant and pregnant (138
      143 days gestation) sheep UA. However, this cortisol-mediated response was
      significantly attenuated by approximately 50% in pregnant UA. The 11 beta
      hydroxysteroid dehydrogenase (11-beta HSD) inhibitor carbenoxolone did not change
      the effect of cortisol in nonpregnant UA but abolished its effect in pregnant UA
      by increasing the NE pD(2) in control tissues from 6.20 +/- 0.05 to 6.59 +/-
      0.11. The apparent dissociation constant value of NE alpha(1)-adrenoceptors was
      not changed by cortisol in pregnant UA but was decreased in nonpregnant UA. There
      was no difference in glucocorticoid receptor density between nonpregnant and
      pregnant UA. Cortisol significantly decreased endothelial nitric oxide (NO)
      synthase protein levels and NO release in both nonpregnant and pregnant UA, but
      the effect of cortisol was attenuated in pregnant UA by approximately 50%.
      Carbenoxolone alone had no effects on NO release in nonpregnant UA but was
      decreased in pregnant UA. These results suggest that cortisol potentiates NE
      mediated contractions by decreasing NO release and increasing NE-binding affinity
      to alpha(1)-adrenoceptors in nonpregnant UA. Pregnancy attenuates UA sensitivity
      to cortisol, which may be mediated by increasing type-2 11-beta HSD activity in
      UA.

PMID- 12063297
TI  - Hypoxic vasorelaxation inhibition by organ culture correlates with loss of Kv
      channels but not Ca(2+) channels.
AB  - We (Thorne GD, Shimizu S, and Paul RJ. Am J Physiol Cell Physiol 281: C24-C32,
      2001) have recently shown that organ culture for 24 h specifically inhibits
      relaxation to acute hypoxia (95% N(2)-5% CO(2)) in the porcine coronary artery.
      Here we show similar results in the porcine carotid artery and the rat and mouse
      aorta. In the coronary artery, part of the inability to relax to hypoxia after
      organ culture is associated with a concomitant loss in ability to reduce
      intracellular Ca(2+) concentration ([Ca(2+)](i)) during hypoxia (Thorne GD,
      Shimizu S, and Paul RJ. Am J Physiol Cell Physiol 281: C24-C32, 2001). To
      elucidate the mechanisms responsible for the loss of relaxation to hypoxia, we
      investigated changes in K(+) and Ca(2+) channel activity and gene expression that
      play key roles in [Ca(2+)](i) regulation in vascular smooth muscle (VSM). Reduced
      mRNA expression of O(2)-sensitive K(+) channels (Kv1.5 and Kv2.1) was shown by
      reverse transcriptase-polymerase chain reaction in the rat aorta. In contrast, no
      change in other expressed voltage-gated K(+) channels (Kv1.2 and Kv1.3) or Ca(2+)
      channel subtypes was found. Modified K(+) channel expression is supported by
      functional evidence indicating a reduced response to general K(+) channel
      activation, by pinacidil, and to specific voltage-dependent K(+) (Kv) channel
      blockade by 4-aminopyridine. In conclusion, organ culture decreases expression of
      specific Kv channels. These changes are consistent with altered mechanisms of VSM
      contractility that may be involved in Ca(2+)-dependent pathways of hypoxia
      induced vasodilation.

PMID- 12063298
TI  - Melatonin as an effective protector against doxorubicin-induced cardiotoxicity.
AB  - The present study was designed to explore the protective effects of melatonin and
      its analogs, 6-hydroxymelatonin and 8-methoxy-2-propionamidotetralin, on the
      survival of doxorubicin-treated mice and on doxorubicin-induced cardiac
      dysfunction, ultrastructural alterations, and apoptosis in mouse hearts. Whereas
      60% of the mice treated with doxorubicin (25 mg/kg ip) died in 5 days, almost all
      the doxorubicin-treated mice survived when melatonin or 6-hydroxymelatonin (10
      mg/l) was administered in their drinking water. Perfusion of mouse hearts with 5
      microM doxorubicin for 60 min led to a 50% suppression of heart rate x left
      ventricular developed pressure and a 50% reduction of coronary flow. Exposure of
      hearts to 1 microM melatonin or 6-hydroxymelatonin reversed doxorubicin-induced
      cardiac dysfunction. 8-Methoxy-2-propionamidotetralin had no protective effects
      on animal survival and on in vitro cardiac function. Infusion of melatonin or 6
      hydroxymelatonin (2.5 microg/h) significantly attenuated doxorubicin-induced
      cardiac dysfunction, ultrastructural alterations, and apoptosis in mouse hearts.
      Neither melatonin nor 6-hydroxymelatonin compromised the antitumor activity of
      doxorubicin in cultured PC-3 cells. These results suggest that melatonin protect
      against doxorubicin-induced cardiotoxicity without interfering with its antitumor
      effect.

PMID- 12063299
TI  - Calpains and cytokines in fibrillating human atria.
AB  - Atrial fibrillation (AF) is accompanied by intracellular calcium overload. The
      purpose of this study was to assess the role of calcium-dependent calpains and
      cytokines during AF. Atrial tissue samples from 32 patients [16 with chronic AF
      and 16 in sinus rhythm (SR)] undergoing open heart surgery were studied. Atrial
      expression of calpain I and II, calpastatin, troponin T (TnT), troponin C (TnC),
      and cytokines [interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, transforming
      growth factor (TGF)-beta 1, and tumor necrosis factor-alpha] were determined.
      Expression of calpain I was increased during AF (461 +/- 201% vs. 100 +/- 34%, P
      < 0.05). Amounts of calpain II and calpastatin were unchanged. Total calpain
      enzymatic activity was more than doubled during AF (35.2 +/- 17.7 vs. 12.4 +/-
      9.2 units, P < 0.05). In contrast to TnC, TnT levels were reduced in fibrillating
      atria by 26% (P < 0.05), corresponding to the myofilament disintegration seen by
      electron microscopy. Small amounts of only IL-2 and TGF-beta 1 mRNA and protein
      were detected regardless of the underlying cardiac rhythm. In conclusion, atria
      of patients with permanent AF show evidence of calpain I activation that might
      contribute to structural remodeling and contractile dysfunction, whereas there is
      no evidence of activation of tissue cytokines.

PMID- 12063300
TI  - Developmental regulation of Na(+)/H(+) exchanger expression in fetal and neonatal
      mice.
AB  - We examined the hypothesis that Na(+)/H(+) exchanger expression is regulated
      during fetal and neonatal development and differentiation. To examine
      transcriptional regulation of the NHE1 isoform of the Na(+)/H(+) exchanger,
      transgenic mice were created that contained the mouse NHE1 promoter driving
      expression of green fluorescent protein. The level of NHE1 transcription varied
      between tissues and with the stage of embryonic development. The highest
      expression was in the heart and liver of 12- to 15-day-old mice, and this
      declined with age. To examine Na(+)/H(+) exchanger protein levels, we
      immunoblotted mouse tissues from 18-day-old embryos, neonates, and adults.
      Protein levels increased after embryonic day 18 and peaked at 14 days of age in
      the heart, lung, liver, kidney, and brain. The greatest rise in NHE1 protein
      expression occurred in the heart, whereas the smallest increase was in the brain.
      The results suggest that Na(+)/H(+) exchanger transcription and protein levels
      are controlled in a tissue-specific and time-dependent manner during development.

PMID- 12063301
TI  - Mechanisms by which opening the mitochondrial ATP- sensitive K(+) channel
      protects the ischemic heart.
AB  - Diazoxide opening of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel
      protects the heart against ischemia-reperfusion injury by unknown mechanisms. We
      investigated the mechanisms by which mitoK(ATP) channel opening may act as an end
      effector of cardioprotection in the perfused rat heart model, in permeabilized
      fibers, and in rat heart mitochondria. We show that diazoxide pretreatment
      preserves the normal low outer membrane permeability to nucleotides and
      cytochrome c and that these beneficial effects are abolished by the mitoK(ATP)
      channel inhibitor 5-hydroxydecanoate. We hypothesize that an open mitoK(ATP)
      channel during ischemia maintains the tight structure of the intermembrane space
      that is required to preserve the normal low outer membrane permeability to ADP
      and ATP. This hypothesis is supported by findings in mitochondria showing that
      small decreases in intermembrane space volume, induced by either osmotic swelling
      or diazoxide, increased the half-saturation constant for ADP stimulation of
      respiration and sharply reduced ATP hydrolysis. These effects are proposed to
      lead to preservation of adenine nucleotides during ischemia and efficient energy
      transfer upon reperfusion.

PMID- 12063302
TI  - Adenosine A(1) receptor mediates late preconditioning via activation of PKC-delta
      signaling pathway.
AB  - Protein kinase C (PKC) plays a central role in both early and late
      preconditioning (PC) but its association with inducible nitric oxide synthase
      (iNOS) is not clear in late PC. This study investigates the PKC signaling pathway
      in the late PC induced by activation of adenosine A(1) receptor (A(1)R) with
      adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and the effect on
      iNOS upregulation. Adult male mice were pretreated with saline or CCPA (100
      microg/kg iv) or CCPA (100 microg/kg iv) with PKC-delta inhibitor rottlerin (50
      microg/kg ip). Twenty-four hours later, the hearts were isolated and perfused in
      the Langendorff mode. Hearts were subjected to 40 min of ischemia, followed by 30
      min reperfusion. After ischemia, the left ventricular end-diastolic pressure
      (LVEDP) was significantly improved and the rate-pressure product (RPP) was
      significantly higher in the CCPA group compared with the ischemia-reperfusion
      (I/R) control group. Creatine kinase release and infarct size were significantly
      lower in the CCPA group compared with the I/R control group. These salutary
      effects of CCPA were abolished in hearts pretreated with rottlerin.
      Immunoblotting of PKC showed that PKC-delta was upregulated (150.0 +/- 11.4% of
      control group) whereas other PKC isoforms remained unchanged, and iNOS was also
      significantly increased (146.2 +/- 9.0%, P < 0.05 vs. control group) after 24 h
      of treatment with CCPA. The data show that PKC is an important component of PC
      with adenosine agonist. It is concluded that activation of A(1)R induces late PC
      via PKC-delta and iNOS signaling pathways.

PMID- 12063303
TI  - Presence of a calcium-activated chloride current in mouse ventricular myocytes.
AB  - The properties of several components of outward K(+) currents, including the
      pharmacological and kinetics profiles as well as the respective molecular
      correlates, have been identified in mouse cardiac myocytes. Surprisingly little
      is known with regard to the Ca(2+)-activated ionic currents. We studied the
      Ca(2+)-activated transient outward currents in mouse ventricular myocytes. We
      have identified a 4-aminopyridine (4-AP)- and tetraethyl ammonium-resistant
      transient outward current that is Ca(2+) dependent. The current is carried by Cl(
      ) and is critically dependent on Ca(2+) influx via voltage-gated Ca(2+) channels
      and the sarcoplasmic reticulum Ca(2+) store. The current can be blocked by the
      anion transport blockers niflumic acid and 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid. Single channel recordings reveal small conductance channels
      (approximately 1 pS in 140 mM Cl(-)) that can be blocked by anion transport
      blockers. Ensemble-averaged current faithfully mirrors the transient kinetics
      observed at the whole level. Niflumic acid (in the presence of 4-AP) leads to
      prolongation of the early repolarization. Thus this current may contribute to
      early repolarization of action potentials in mouse ventricular myocytes.

PMID- 12063305
TI  - Energetics of the Frank-Starling effect in rabbit myocardium: economy and
      efficiency depend on muscle length.
AB  - We tested the hypothesis that economy and efficiency are independent of length in
      intact cardiac muscle over its normal working range. We measured force, force
      time integral, force-length area, and myocardial oxygen consumption in eight
      isometrically contracting rabbit right ventricular papillary muscles. 2,3
      Butanedione monoxime was used to partition nonbasal oxygen consumption into
      tension-independent and tension-dependent components. Developed force, force-time
      integral, and force-length area increased by factors of 2.4, 2.7, and 4.8,
      respectively, as muscle length was increased from 90% to 100% maximal length,
      whereas tension-dependent oxygen consumption increased only 1.6-fold. Economy
      (the ratio of force-time integral to tension-dependent oxygen consumption)
      increased significantly with muscle length, as did contractile efficiency, the
      ratio of force-length area to tension-dependent oxygen consumption. The average
      force-length area-nonbasal oxygen consumption intercept was more than the twice
      tension-independent oxygen consumption. We conclude that economy and efficiency
      increase with length in rabbit myocardium. This conclusion is consistent with
      published data in isolated rabbit and dog hearts but at odds with studies in
      skinned myocardium.

PMID- 12063304
TI  - Cerebrovascular autoregulation is profoundly impaired in mice overexpressing
      amyloid precursor protein.
AB  - The amyloid-beta (A beta) peptide, which is derived from the amyloid precursor
      protein (APP), is involved in the pathogenesis of Alzheimer's dementia and
      impairs endothelium-dependent vasodilation in cerebral vessels. We investigated
      whether cerebrovascular autoregulation, i.e., the ability of the cerebral
      circulation to maintain flow in the face of changes in mean arterial pressure
      (MAP), is impaired in transgenic mice that overexpress APP and A beta.
      Neocortical cerebral blood flow (CBF) was monitored by laser-Doppler flowmetry in
      anesthetized APP(+) and APP(-) mice. MAP was elevated by intravenous infusion of
      phenylephrine and reduced by controlled exsanguination. In APP(-) mice,
      autoregulation was preserved. However, in APP(+) mice, autoregulation was
      markedly disrupted. The magnitude of the disruption was linearly related to brain
      A beta concentration. The failure of autoregulation was paralleled by impairment
      of the CBF response to endothelium-dependent vasodilators. Thus A beta disrupts a
      critical homeostatic mechanism of the cerebral circulation and renders CBF highly
      dependent on MAP. The resulting alterations in cerebral perfusion may play a role
      in the brain dysfunction and periventricular white-matter changes associated with
      Alzheimer's dementia.

PMID- 12063306
TI  - Activation of cardiac ryanodine receptors by the calcium channel agonist FPL
      64176.
AB  - We investigated the possibility that the Ca(2+) channel agonist FPL-64176 (FPL)
      might also activate the cardiac sarcoplasmic reticulum (SR) Ca(2+) release
      channel ryanodine receptor (RyR). The effects of FPL were tested on single
      channel activity of purified and crude vesicular RyR (RyR2) isolated from human
      and dog hearts using the planar lipid bilayer technique. FPL (100-200 microM)
      increased single channel open probability (P(o)) when added to the cytoplasmic
      side of the channel (P(o) = 0.070 +/- 0.021 in control RyR2; 0.378 +/- 0.086 in
      150 microM FPL, n = 9, P < 0.01) by prolonging open times and decreasing closed
      times without changing current magnitude. FPL had no effect on P(o) when added to
      the trans (luminal) side of the bilayer (P(o) = 0.079 +/- 0.036 in control and
      0.103 +/- 0.066 in FPL, n = 4, no significant difference). The bell-shaped
      [Ca(2+)] dependence of [(3)H]ryanodine binding and of P(o) was altered by FPL,
      suggesting that the mechanism by which FPL increases channel activity is by an
      increase in Ca(2+)-induced activation at low [Ca(2+)] (without a change in
      threshold) and suppression of Ca(2+)-induced inactivation at high [Ca(2+)].
      However, the fact that inactivation was restored at elevated [Ca(2+)] suggests a
      competitive interaction between Ca(2+) and FPL on inactivation. FPL had no effect
      on RyR skeletal channels (RyR1), where P(o) was 0.039 +/- 0.005 in control versus
      0.030 +/- 0.006 in 150 microM FPL (no significant difference). These results
      suggest that, in addition to its ability to activate the L-type Ca(2+) channels,
      FPL activates cardiac RyR2 primarily by reducing the Ca(2+) sensitivity of
      inactivation.

PMID- 12063307
TI  - Inhibition of NOS II prevents cardiac dysfunction in myocardial infarction and
      congestive heart failure.
AB  - Strong expression of the inducible form of nitric oxide synthase (NOS II) has
      been shown in the myocardium of patients with myocardial infarction (MI). We
      hypothesized that NOS II plays an important role in the development of MI and
      subsequent heart failure and that inhibition of NOS II may beneficially alter the
      course of the disease. Long-term administration (2 mo) of the selective NOS II
      inhibitor S-methylisothiourea (SMT) to rats with MI significantly improved
      cardiac function. A significant drop in mortality, lung water content, infarct
      size, and cardiomyocyte hypertrophy was also associated with the use of SMT.
      Plasma concentration of nitrite and nitrate was also reduced by SMT. Short-term
      administration of SMT (first 2 wk only) significantly reduced infarct size;
      however, it did not improve cardiac dysfunction measured 2 mo after MI. These
      findings demonstrate that induction of NOS II during MI exerts negative effects
      on cardiac function and structure. Long-term administration of a selective NOS II
      inhibitor may prove to be beneficial in the treatment of MI and congestive heart
      failure.

PMID- 12063308
TI  - Doppler echocardiographic estimation of left ventricular end-diastolic pressure
      after MI in rats.
AB  - The spectral Doppler mitral flow pattern, alone or combined with tissue Doppler
      mitral annulus velocity, can be used to predict left ventricular (LV) filling
      pressure in humans, whereas invasive hemodynamic measurements are still required
      in the rat. This study was undertaken to assess whether LV end-diastolic pressure
      (LVEDP) can be estimated using Doppler echocardiography in the rat after
      myocardial infarction (MI). Thirty-seven rats (23 rats with MI after left
      coronary artery ligation and 14 sham-operated rats) were evaluated 3 mo after
      surgery with echo-Doppler and invasive hemodynamic measurements. Pulse wave
      spectral Doppler at the mitral valve tip was used to measure the E wave, the E
      wave deceleration time (DT), and the A wave; spectral Doppler tissue imaging was
      used to measure the early diastolic lateral mitral annulus velocity (E(a)). We
      found weak correlations between LVEDP and the peak velocity of the early mitral
      inflow (E), E/peak velocity of the late mitral inflow, and DT, and strong
      correlations with E(a) and especially with E/E(a) [R(2) = 0.89, LVEDP (in mmHg) =
      0.987E/E(a) - 4.229]. Longitudinal followup of a subgroup of rats with MI
      revealed a marked rise of E/E(a) between days 7 and 21 in rats with heart failure
      only. We conclude that Doppler echocardiography can be used for serial assessment
      of LV diastolic function in rats with MI.

PMID- 12063309
TI  - High-salt diet depresses acetylcholine reactivity proximal to NOS activation in
      cerebral arteries.
AB  - Rats were fed a low-salt (LS; 0.4% NaCl) or high-salt (HS; 4.0% NaCl) diet for 3
      days, and the responses of isolated cerebral arteries to acetylcholine (ACh), the
      nitric oxide (NO)-dependent dilator bradykinin, and the NO donor 6-(2-hydroxy-1
      methyl-2-nitrosohydrazino)-N-methyl-1-hex-anamine (NOC-9) were determined. ACh
      induced vasodilation and NO release, assessed with the fluorescent NO indicator
      4,5-diaminofluorescein (DAF-2) diacetate, were eliminated with the HS diet.
      Inhibition of cyclooxygenase, cytochrome P-450 epoxygenase, and
      acetylcholinesterase did not alter ACh responses. Bradykinin and NOC-9 caused a
      similar dilation in cerebral arteries of all groups. Arteries from animals on LS
      or HS diets exhibited similar levels of basal superoxide (O(2)(-)) production,
      assessed by dihydroethidine fluorescence, and ACh responses were unaffected by
      O(2)(-) scavengers. Muscarinic type 3 receptor expression was unaffected by
      dietary salt intake. These results indicate that 1) a HS diet attenuates ACh
      reactivity in cerebral arteries by inhibiting NO release, 2) this attenuation is
      not due to production of a cyclooxygenase-derived vasoconstrictor or elevated
      O(2)(-) levels, and 3) alteration(s) in ACh signaling are located upstream from
      NO synthase.

PMID- 12063311
TI  - Correlation of repolarization of ventricular monophasic action potential with ECG
      in the murine heart.
AB  - Transgenic mice have become important experimental models in the investigation of
      mechanisms causing cardiac arrhythmias because of the ability to create strains
      with alterations in repolarizing membrane currents. It is important to relate
      alterations in membrane currents in cells to their phenotypic expression on the
      electrocardiogram (ECG). The murine ECG, however, has unusual characteristics
      that make interpretation of the phenotypic expression of changes in ventricular
      repolarization uncertain. The major deflection representing the QRS (referred to
      as "a") is often followed by a secondary slower deflection ("b") and sometimes a
      subtle third deflection ("c"). To determine whether the second or third
      deflections or both represent ventricular repolarization, we recorded the
      ventricular monophasic action potential (MAP) in open-chest mice and correlated
      repolarization with the ECG. There was no significant correlation by linear
      regression, between action potential duration to 50% or 90% repolarization
      (APD(50) or APD(90)), respectively, of the MAP and either the interval from onset
      of Q to onset of b (Qb interval) or onset of c (Qc interval). Administration of 4
      aminopyridine (4-AP) significantly prolonged APD(50) and APD(90) and the Qb
      interval, indicating that this deflection on the ECG represents part of
      ventricular repolarization. After 4-AP, the c wave disappeared, also suggesting
      that it represents a component of ventricular repolarization. Although it appears
      that both the b and c waves that follow the Q wave on the ECG represent
      ventricular repolarization, neither correlates exactly with APD(90) of the MAP.
      Therefore, an accurate measurement of complete repolarization of the murine
      ventricle cannot be obtained from the surface ECG.

PMID- 12063310
TI  - Serial noninvasive assessment of progressive pulmonary hypertension in a rat
      model.
AB  - Current methods used to investigate pulmonary hypertension in rat models of the
      disease allow for only one to two measurements of pulmonary artery (PA) pressure
      in the life of a rat. We investigated whether transthoracic echocardiography can
      be used to assess the progression of pulmonary hypertension in rats at multiple
      time points. Serial echocardiographic measurements were performed over a 6-wk
      period on rats injected with monocrotaline (MCT) or placebo. Development of a
      midsystolic notch in the PA waveform, a decrease in the PA flow acceleration time
      (PAAT), an increase in right ventricular (RV) free-wall thickness, and the
      development of tricuspid regurgitation (TR) were observed as pulmonary
      hypertension developed. Changes in the PA waveform and PAAT began in week 3 of
      disease development as the PA systolic pressure (PASP) reached 25-30 mmHg
      according to right heart catheterization. The RV free-wall thickness increased
      significantly by week 5 (PASPs 40-50 mmHg). Development of quantifiable TR
      occurred in week 6 or at PASPs > 65 mmHg. A linear correlation was found between
      the PAAT and PASP in the range of 30-65 mmHg and between the RV-right atrial
      pressure gradient (derived from TR velocity) and PASP at pressures >65 mmHg,
      which enabled a noninvasive estimate of the PASP over a wide range of pressures
      based on these parameters. These data indicate that transthoracic
      echocardiography can be used for monitoring the progress of pulmonary
      hypertension in a rat model.

PMID- 12063312
TI  - Superoxide anion impairs contractility in cultured aortic smooth muscle cells.
AB  - We examined the effects of superoxide anion (O) generated by xanthine plus
      xanthine oxidase (X/XO) on the intracellular Ca(2+) concentration ([Ca(2+)](i))
      and muscle contractility in cultured bovine aortic smooth muscle cells (BASMC).
      Cells were grown on collagen-coated dish for the measurement of [Ca(2+)](i).
      Pretreatment with X/XO inhibited ATP-induced Ca(2+) transient and Ca(2+) release
      activated Ca(2+) entry (CRAC) after thapsigargin-induced store depletion, both of
      which were reversed by superoxide dismutase (SOD). In contrast, Ca(2+) transients
      induced by high-K(+) solution and Ca(2+) ionophore A-23187 were not affected by
      X/XO. BASMC-embedded collagen gel lattice, which was pretreated with xanthine
      alone, showed contraction in response to ATP, thapsigargin, high-K(+) solution,
      and A-23187. Pretreatment of the gel with X/XO impaired gel contraction not only
      by ATP and thapsigargin, but also by high-K(+) solution and A-23187. The X/XO
      treated gel showed normal contraction; however, when SOD was present during the
      pretreatment period. These results indicate that O(2)(-) attenuates smooth muscle
      contraction by impairing CRAC, ATP-induced Ca(2+) transient, and Ca(2+)
      sensitivity in BASMC.

PMID- 12063313
TI  - Obesity lowers hyperglycemic threshold for impaired in vivo endothelial nitric
      oxide function.
AB  - Obesity is a risk for type II diabetes mellitus and increased vascular
      resistance. Disturbances of nitric oxide (NO) physiology occur in both obese
      animals and humans. In obese Zucker rats, we determined whether a protein kinase
      C-beta II (PKC-beta II) mechanism may lower the resting NO concentration ([NO])
      and predispose endothelial NO abnormalities at lower glucose concentrations than
      occur in lean rats. NO was measured with microelectrodes touching in vivo
      intestinal arterioles. At rest, the [NO] in obese Zucker rats was 60 nm less than
      normal or about a 15% decline. After local blockade of PKC-beta II with LY
      333531, the [NO] increased approximately 90 nm in obese rats but did not change
      in lean rats. In lean rats, administration of 300 mg/dl D-glucose for 45 min
      depressed endothelium-dependent dilation; only 200 mg/dl was required in obese
      animals. These various observations indicate that resting [NO] is depressed in
      obese rats by a PKC-beta II mechanism and the hyperglycemic threshold for
      endothelial NO suppression is reduced to 200 mg/dl D-glucose.

PMID- 12063314
TI  - Interaction of albumin with the endothelial cell surface.
AB  - Endothelial cells (EC) are covered with cell-borne proteoglycans and
      glycoproteins. Blood plasma proteins (e.g., albumin) adsorb to this glycocalyx
      forming a complex endothelial surface layer (ESL). We determined the molecular
      mobility of albumin by electron spin resonance (ESR) in the presence and absence
      of ECs to analyze interactions with the ESL. Albumin was spin labeled with 5- or
      12-4,4-dimethyloxazolidine-N-oxyl (DOXYL)-stearic acid yielding information on
      the mobility of the molecular surface (5-DOXYL) or the entire protein (12-DOXYL).
      EC cultures grown on glass coverslips were immersed in labeled albumin and placed
      in the temperature-regulated cavity of an ESR spectrometer. Alternatively, ECs
      were labeled and then exposed to native albumin. At 37 degrees C, rotational
      correlation times determined by modified saturation transfer ESR (ST-ESR) were 26
      and 48 ns for 5-DOXYL- and 12-DOXYL-labeled albumin, respectively. Presence of
      ECs increased rotational correlation time values for 5-DOXYL-stearic acid to 37
      ns but not for 12-DOXYL-stearic acid. Albumin was able to completely take up the
      label from labeled EC within 2 min. The present study shows that modified ST-ESR
      can be used to determine the mobility of biological macromolecules interacting
      with cellular surfaces. Reduction in albumin surface mobility in the presence of
      EC at unchanged mobility of protein proper and fast removal of labeled fatty
      acids from EC membranes indicate rapid transient interactions between albumin
      surface and ESL but no rigid incorporation of albumin into a macromolecular
      network that would interfere with its transport function for poorly water-soluble
      substances.

PMID- 12063315
TI  - Hydrogen peroxide acts as an EDHF in the piglet pial vasculature in response to
      bradykinin.
AB  - We investigated the mechanism of EDHF-mediated dilation to bradykinin (BK) in
      piglet pial arteries. Topically applied BK (3 micromol/l) induced vasodilation
      (62 +/- 12%) after the administration of N(omega)-nitro-L-arginine methyl ester
      (L-NAME) and indomethacin, which was inhibited by endothelial impairment or by
      the BK(2) receptor antagonist HOE-140 (0.3 micromol/l). Western blotting showed
      the presence of BK(2) receptors in brain cortex and pial vascular tissue samples.
      The cytochrome P-450 antagonist miconazole (20 micromol/l) and the lipoxygenase
      inhibitors baicalein (10 micromol/l) and cinnamyl-3,4-dyhydroxy-alpha
      cyanocinnamate (1 micromol/l) failed to reduce the BK-induced dilation. However,
      the H(2)O(2) scavenger catalase (400 U/ml) abolished the response (from 54 +/- 11
      to 0 +/- 2 microm; P < 0.01). The ATP-dependent K(+) (K(ATP)) channel inhibitor
      glibenclamide (10 micromol/l) had a similar effect as well (from 54 +/- 11 to 16
      +/- 5 microm; P < 0.05). Coapplication of the Ca(2+)-dependent K(+) channel
      inhibitors charybdotoxin (0.1 micromol/l) and apamin (0.5 micromol/l) failed to
      reduce the response. We conclude that H(2)O(2) mediates the non-nitric oxide-,
      non-prostanoid-dependent vasorelaxation to BK in the piglet pial vasculature. The
      response is mediated via BK(2) receptors and the opening of K(ATP) channels.

PMID- 12063316
TI  - Electrophysiological response of rat ventricular myocytes to acidosis.
AB  - The effects of acidosis on the action potential, resting potential, L-type Ca(2+)
      (I(Ca)), inward rectifier potassium (I(K1)), delayed rectifier potassium (I(K)),
      steady-state (I(SS)), and inwardly rectifying chloride (I(Cl,ir)) currents of rat
      subepicardial (Epi) and subendocardial (Endo) ventricular myocytes were
      investigated using the patch-clamp technique. Action potential duration was
      shorter in Epi than in Endo cells. Acidosis (extracellular pH decreased from 7.4
      to 6.5) depolarized the resting membrane potential and prolonged the time for 50%
      repolarization of the action potential in Epi and Endo cells, although the
      prolongation was larger in Endo cells. At control pH, I(Ca), I(K1), and I(SS)
      were not significantly different in Epi and Endo cells, but I(K) was larger in
      Epi cells. Acidosis did not alter I(Ca), I(K1), or I(K) but decreased I(SS); this
      decrease was larger in Endo cells. It is suggested that the acidosis-induced
      decrease in I(SS) underlies the prolongation of the action potential. I(Cl,ir) at
      control pH was Cd(2+) sensitive but 4,4'-disothiocyanato-stilbene-2,2'-disulfonic
      acid resistant. Acidosis increased I(Cl,ir); it is suggested that the acidosis
      induced increase in I(Cl,ir) underlies the depolarization of the resting membrane
      potential.

PMID- 12063318
TI  - Evidence for fractal correlation properties in variations of peripheral arterial
      tone during REM sleep.
AB  - Previous studies utilizing detrended fluctuation analysis (DFA) of heart rate
      variability during sleep revealed a higher fractal exponent during rapid eye
      movement (REM) sleep than non-REM sleep. The aim of this study was to determine
      whether the same difference exists in the variations of peripheral arterial tone
      (PAT). Finger pulse wave measured by a novel plethysmographic technique was
      monitored during sleep in 12 chronic heart failure patients, 8 heavy snorers, and
      12 healthy volunteers. For each subject, at least two 15-min time series were
      constructed from the interpulse intervals and from pulse wave amplitudes during
      REM and non-REM sleep. Fractal scaling exponents of both types of time series
      were significantly higher for REM than non-REM sleep in all groups. In each of
      the groups and in both sleep stages, the fractal scaling exponents based on pulse
      wave amplitude were significantly higher than those based on pulse rate
      variability. A repeat of the analysis for short-, intermediate-, and long-term
      intervals revealed that the fractal-like exponents were evident only in the short
      and intermediate-term intervals. Because PAT is a surrogate of sympathetic
      activation, our results indicate that variations in sympathetic activation during
      REM sleep have a fractal-like behavior.

PMID- 12063317
TI  - The renin-angiotensin-aldosterone system excites hypothalamic paraventricular
      nucleus neurons in heart failure.
AB  - The paraventricular nucleus (PVN) of the hypothalamus has critical homeostatic
      functions, including the regulation of fluid balance and sympathetic drive. It
      has been suggested that altered activity of this nucleus contributes to the
      progression of congestive heart failure (HF). We hypothesized that forebrain
      influences of the renin-angiotensin-aldosterone system augment the activity of
      PVN neurons in HF. The rate of PVN neurons (n = 68) from rats with ischemia
      induced HF was higher than that of PVN neurons (n = 42) from sham-operated
      controls (8.7 +/- 0.8 vs. 2.7 +/- 0.3 spikes/s, P < 0.001, HF vs. SHAM).
      Forebrain-directed intracarotid artery injections of the angiotensin type 1
      receptor antagonist losartan, the angiotensin-converting enzyme inhibitor
      captopril, and the mineralocorticoid receptor antagonist spironolactone all
      significantly (P < 0.05) reduced PVN neuronal activity in HF rats. These findings
      demonstrate that the renin-angiotensin-aldosterone system drives PVN neuronal
      activity in HF, likely resulting in increased sympathetic drive and volume
      accumulation. This mechanism of neurohumoral excitation in HF is accessible to
      manipulation by blood-borne therapeutic agents.

PMID- 12063319
TI  - Opening of mitochondrial K(ATP) channel occurs downstream of PKC-epsilon
      activation in the mechanism of preconditioning.
AB  - We examined whether the mitochondrial ATP-sensitive K channel (K(ATP)) is an
      effector downstream of protein kinase C-epsilon (PKC-epsilon) in the mechanism of
      preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min
      ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from
      50.3 +/- 6.8% of the left ventricle to 20.3 +/- 3.7%. PC significantly increased
      PKC-epsilon protein in the particulate fraction from 51 +/- 4% of the total to 60
      +/- 4%, whereas no translocation was observed for PKC-delta and PKC-alpha. In
      mitochondria separated from the other particulate fractions, PC increased the PKC
      epsilon level by 50%. Infusion of 5-hydroxydecanoate (5-HD), a mitochondrial
      K(ATP) blocker, after PC abolished the cardioprotection of PC, whereas PKC
      epsilon translocation by PC was not interfered with 5-HD. Diazoxide, a
      mitochondrial K(ATP) opener, infused 10 min before ischemia limited infarct size
      to 5.2 +/- 1.4%, but this agent neither translocated PKC-epsilon by itself nor
      accelerated PKC-epsilon translocation after ischemia. Together with the results
      of earlier studies showing mitochondrial K(ATP) opening by PKC, the present
      results suggest that mitochondrial K(ATP)-mediated cardioprotection occurs
      subsequent to PKC-epsilon activation by PC.

PMID- 12063320
TI  - Electrical refractory period restitution and spiral wave reentry in simulated
      cardiac tissue.
AB  - Theoretical and experimental studies have shown that restitution of the cardiac
      action potential (AP) duration (APD) plays a major role in predisposing
      ventricular tachycardia to degenerate to ventricular fibrillation, whereas its
      role in atrial fibrillation is unclear. We used the Courtemanche human atrial
      cell model and the Luo-Rudy guinea pig ventricular model to compare the roles of
      electrical restitution in destabilizing spiral wave reentry in simulated two
      dimensional homogeneous atrial and ventricular tissue. Because atrial AP
      morphology is complex, we also validated the usefulness of effective refractory
      period (ERP) restitution. ERP restitution correlated best with APD restitution at
      transmembrane potentials greater than or equal to -62 mV, and its steepness was a
      reliable predictor of spiral wave phenotype (stable, meandering, hypermeandering,
      and breakup) in both atrial and ventricular tissue. Spiral breakup or single
      hypermeandering spirals occurred when the slope of ERP restitution exceeded 1 at
      short diastolic intervals. Thus ERP restitution, which is easier to measure
      clinically than APD restitution, is a reliable determinant of spiral wave
      stability in simulated atrial and ventricular tissue.

PMID- 12063322
TI  - Rapid polyethylene failure of unicondylar tibial components sterilized with gamma
      irradiation in air and implanted after a long shelf life.
AB  - BACKGROUND: The mechanical toughness of polyethylene that has been sterilized by
      gamma irradiation in air decreases after a long shelf life. The purpose of the
      present study is to report the high failure rate after unicondylar knee
      replacements performed with polyethylene bearings that had been sterilized with
      gamma irradiation in air and implanted after a shelf life of < or = 4.4 years.
      METHODS: Between December 1997 and January 2000, seventy-five unicondylar knee
      replacements were performed in sixty-two patients. All patients were followed
      both clinically and radiographically. A revision operation was offered when the
      patient had pain, swelling, and radiographic evidence of rapid polyethylene wear.
      The effect of aging of the polyethylene during storage was evaluated by dividing
      the knees into three groups on the basis of shelf life and comparing them with
      regard to the rate of revision and the observed wear of the polyethylene. Four
      retrieved components were examined for the presence of oxidation. RESULTS: At a
      mean of eighteen months after the arthroplasty, thirty knees had been revised and
      seven were scheduled for revision. The rate of polyethylene wear increased as the
      shelf life increased. There was a significant inverse linear correlation between
      the shelf life of the polyethylene and the time to revision (p < 0.01, r (2) =
      0.64). All retrieved components had greater-than-expected wear with pitting and
      delamination of the surface. Seven components had fractured, and ten had both
      fractured and fragmented. Analysis of four components confirmed severe oxidation
      of the polyethylene. CONCLUSION: The present study demonstrated early, severe
      wear of tibial polyethylene bearings that had been sterilized by gamma
      irradiation in air and stored for < or = 4.4 years. This risk can be minimized by
      ensuring that implants have not been sterilized with gamma irradiation in air and
      stored for several years.

PMID- 12063323
TI  - The effectiveness of reconstruction of the anterior cruciate ligament with
      hamstrings and patellar tendon . A cadaveric study comparing anterior tibial and
      rotational loads.
AB  - BACKGROUND: The objective of this study was to evaluate the effectiveness of
      reconstructions of the anterior cruciate ligament to resist anterior tibial and
      rotational loads. We hypothesized that current reconstruction techniques, which
      are designed mainly to provide resistance to anterior tibial loads, are less
      effective in limiting knee instability in response to combined rotational loads.
      METHODS: Twelve fresh-frozen young human cadaveric knees (from individuals with a
      mean age [and standard deviation] of 37 +/- 13 years at the time of death) were
      tested with use of a robotic/universal force-moment sensor testing system. The
      loading conditions included (1) a 134-N anterior tibial load with the knee at
      full extension and at 15 degrees, 30 degrees, and 90 degrees of flexion, and (2)
      a combined rotational load of 10 N-m of valgus torque and 10 N-m of internal
      tibial torque with the knee at 15 degrees and 30 degrees of flexion. The
      kinematics of the knees with an intact and a deficient anterior cruciate
      ligament, as well as the in situ force in the intact anterior cruciate ligament,
      were determined in response to both loads. Each knee then underwent
      reconstruction of the anterior cruciate ligament with use of a quadruple
      semitendinosus-gracilis tendon graft and was tested. A second reconstruction was
      performed with a bone-patellar tendon-bone graft, and the same knee was tested
      again. The kinematics of the reconstructed knees and the in situ forces in both
      grafts were determined. RESULTS: The results demonstrated that both
      reconstructions were successful in limiting anterior tibial translation under
      anterior tibial loads. Furthermore, the mean in situ forces in the grafts under a
      134-N anterior tibial load were restored to within 78% to 100% of that in the
      intact knee. However, in response to a combined rotational load, reconstruction
      with either of the two grafts was not as effective in reducing anterior tibial
      translation. This insufficiency was further revealed by the lower in situ forces
      in the grafts, which ranged from 45% to 65% of that in the intact knee.
      CONCLUSIONS: In current reconstruction procedures, the graft is placed close to
      the central axis of the tibia and femur, which makes it inadequate for resisting
      rotational loads. Our findings suggest that improved reconstruction procedures
      that restore the anatomy of the anterior cruciate ligament may be needed.

PMID- 12063325
TI  - Treatment of active unicameral bone cysts with percutaneous injection of
      demineralized bone matrix and autogenous bone marrow.
AB  - BACKGROUND: The treatment of unicameral bone cysts varies from open bone-grafting
      procedures to percutaneous injection of corticosteroids or bone marrow. The
      purpose of this study was to evaluate the feasibility and effectiveness of
      percutaneous injection of a mixture of demineralized bone matrix and autogenous
      bone marrow for the treatment of simple bone cysts. METHODS: Twenty-three
      patients with an active unicameral bone cyst were treated with trephination and
      injection of allogeneic demineralized bone matrix and autogenous bone marrow. The
      patients were followed for an average of fifty months (range, thirty to eighty
      one months), at which time pain, function, and radiographic signs of resolution
      of the cyst were assessed. RESULTS: The average time until the patients had pain
      relief was five weeks, and the average time until the patients returned to full,
      unrestricted activities was six weeks. Bone-healing at the site of the injection
      was first seen radiographically at three to six months. No patient had a
      pathologic fracture during this early bone-healing stage. Cortical remodeling was
      seen radiographically by six to nine months, and after one year the response was
      usually complete, changing very little from then on. Five patients required a
      second injection because of recurrence of the cyst, and all five had a clinically
      and radiographically quiescent cyst after an average of thirty-six additional
      months of follow-up. Seven of the twenty-three patients had incomplete healing
      manifested by small, persistent radiolucent areas within the original cyst. None
      of these cysts increased in size or resulted in pain or fracture. CONCLUSIONS:
      Percutaneous injection of allogeneic demineralized bone matrix and autogenous
      bone marrow is an effective treatment for unicameral bone cysts.

PMID- 12063326
TI  - Femoral lengthening over a humeral intramedullary nail in preadolescent children.
AB  - BACKGROUND: Femoral lengthening over an intramedullary nail has been described in
      adults. A technique of femoral lengthening over a humeral intramedullary nail in
      children is described, and the results and complications are presented. METHODS:
      Nine preadolescent patients (average age, nine years and ten months) with femoral
      length discrepancy were treated with femoral lengthening over a humeral
      intramedullary nail. After nail insertion, a monolateral external fixator was
      placed with half-pins either anterior or posterior to the intramedullary nail,
      and lengthening was performed through a proximal osteotomy. RESULTS: The femora
      were lengthened a mean of 6.1 cm (range, 5.0 to 8.0 cm), 19.5% (range, 15.9% to
      26.2%) of the preoperative femoral length. Patients had a mean lengthening index
      of 12.2 days/cm of length (range, 9.5 to 16.9 days/cm of length). Five
      complications including osteomyelitis, failure of the distal interlocking site,
      and femoral fracture at the distal end of the nail occurred in four patients;
      four of the complications led to surgical intervention. No case of proximal
      femoral valgus secondary to nailing through the greater trochanter had developed
      by the time of final follow-up. All patients were followed for a minimum of two
      years postoperatively, with a mean of 128 weeks (range, 111 to 161 weeks).
      CONCLUSIONS: The technique is effective but has a high rate of complications,
      including osteomyelitis, which developed in two of the nine patients. No
      avascular necrosis or proximal femoral valgus was noted.

PMID- 12063324
TI  - Surgical treatment of nonunion and avascular necrosis of the proximal part of the
      scaphoid in adolescents.
AB  - BACKGROUND: The purpose of this retrospective study was to examine the clinical
      and radiographic results of treatment of proximal scaphoid nonunion and avascular
      necrosis with vascularized bone graft from the distal part of the radius in
      adolescent patients. METHODS: Between 1993 and 1996, three adolescents with a
      proximal scaphoid nonunion and avascular necrosis underwent vascularized bone
      grafting and internal fixation. The mean age at the time of the fracture was 14.8
      years (14.4, 14.6, and 15.3 years), and the mean time interval between the
      fracture and the surgery was 19.3 months (six, seventeen, and thirty-five
      months). We retrospectively reviewed all available clinical and radiographic data
      from the time of fracture to the time of the last follow-up. All patients were
      examined clinically and radiographically at the time of the review, at a mean of
      5.5 years (five, five, and 6.5 years) after surgery. RESULTS: All fractures
      healed at a mean of 3.4 months (2.75, 3.0, and 4.5 months) postoperatively. Final
      follow-up radiographs showed union and revascularization of the proximal part of
      the scaphoid with no evidence of degeneration of the radiocarpal joint. None of
      the patients had limiting pain or scapholunate instability demonstrated on
      physical or radiographic examination. Dorsiflexion and radial deviation of the
      affected wrist were decreased by a mean of 22 degrees (10 degrees, 22 degrees,
      and 35 degrees ) and 15 degrees (5 degrees, 20 degrees, and 20 degrees ),
      respectively, compared with those of the normal wrist. CONCLUSION: Grafting with
      vascularized radial bone is an effective treatment, leading to union and good
      function, for nonunion and avascular necrosis of the proximal part of the
      scaphoid in adolescents.

PMID- 12063327
TI  - Biomechanical comparison of tibial inlay and tibial tunnel techniques for
      reconstruction of the posterior cruciate ligament. Analysis of graft forces.
AB  - BACKGROUND: The tibial inlay technique of reconstruction of the posterior
      cruciate ligament offers potential advantages over the conventional transtibial
      tunnel technique, particularly with regard to the graft force levels that develop
      over a functional range of knee flexion. Abnormally high graft forces generated
      during rehabilitation activities could lead to stretch-out of the graft during
      the critical early healing period. The purpose of this study was to compare graft
      forces between these two techniques and with forces in the native posterior
      cruciate ligament. METHODS: A load cell was installed at the femoral origin of
      the posterior cruciate ligament in twelve fresh-frozen cadaveric knees to measure
      resultant forces in the ligament during a series of knee loading tests. The
      posterior cruciate ligament was then excised, and the femoral ends of 10-mm-wide
      bone-patellar tendon-bone grafts were attached to the load cell to measure
      resultant forces in the grafts. For the tunnel reconstruction, the distal bone
      block of the graft was placed into a tibial tunnel and thin stainless-steel
      cables interwoven into the bone block were gripped in a split clamp attached to
      the anterior tibial cortex. With the inlay technique, the distal bone block was
      fixed in a tibial trough with use of a cortical bone screw with a washer and nut.
      The proximal ends of all grafts were pretensioned to a level of force that
      restored intact knee laxity at 90 degrees of flexion, and loading tests were
      repeated. RESULTS: There were no significant differences in mean graft forces
      between the two techniques under tibial loads consisting of 100 N of posterior
      tibial force, 5 N-m of varus and valgus moment, and 5 N-m of internal and
      external tibial torque. Mean graft forces with the tibial tunnel technique were
      approximately 10 to 20 N higher than those with the inlay technique with passive
      knee flexion beyond 95 degrees. Mean graft forces with both reconstruction
      techniques were significantly higher than forces in the native posterior cruciate
      ligament with the knee flexed beyond approximately 90 degrees for all but one
      mode of loading. CONCLUSIONS: In this cadaveric testing model, neither technique
      for reconstruction of the posterior cruciate ligament had a substantial advantage
      over the other with respect to generation of graft forces.

PMID- 12063328
TI  - Periprosthetic femoral fractures around well-fixed implants: use of cortical
      onlay allografts with or without a plate.
AB  - BACKGROUND: Periprosthetic femoral fractures around hip replacements are
      increasingly common. When the femoral component is stable, open reduction and
      internal fixation is recommended in all but exceptional cases. The purpose of
      this study was to evaluate the outcome of treatment of fractures around stable
      implants with cortical onlay strut allografts with or without a plate. METHODS: A
      survey of our four centers identified forty patients with a fracture around a
      well-fixed femoral stem treated with cortical onlay strut allografts without
      revision of the femoral component. There were fourteen men and twenty-six women,
      with an average age of sixty-nine years. Nineteen patients were treated with
      cortical onlay strut allografts alone, and twenty-one were managed with a plate
      and one or two cortical struts. All of the patients were followed until fracture
      union or until a reoperation was done. The mean duration of follow-up was twenty
      eight months for thirty-nine patients. One patient, who was noncompliant with
      treatment recommendations, had a failure at two months because of a fracture of
      the plate and graft. The primary end point of the evaluation was fracture union;
      secondary end points included strut-to-host bone union, the amount of final bone
      stock, and postoperative function. RESULTS: Thirty-nine (98%) of the forty
      fractures united, and strut-to-host bone union was typically seen within the
      first year. There were four malunions, all of which had <10 degrees of
      malalignment, and one deep infection. There was no evidence of femoral loosening
      in any patient. All but one of the surviving patients returned to their
      preoperative functional level within one year. CONCLUSIONS: Cortical onlay strut
      allografts act as biological bone plates, serving both a mechanical and a
      biological function. The use of cortical struts, either alone or in conjunction
      with a plate, led to a very high rate of fracture union, satisfactory alignment,
      and an increase in femoral bone stock at the time of short-term follow-up.
      Although this study did not address the potential for later allograft remodeling,
      our findings suggest that cortical strut grafts should be used routinely to
      augment fixation and healing of a periprosthetic femoral fracture.

PMID- 12063329
TI  - Biomechanical evaluation of proximal humeral fracture fixation supplemented with
      calcium phosphate cement.
AB  - BACKGROUND: Proximal humeral fractures are common injuries, and numerous surgical
      methods have been described for their treatment. The biomechanical
      characteristics of various internal fixation devices that are used to treat these
      fractures have not been extensively studied, nor has the potential beneficial
      effect of calcium phosphate cement supplementation. METHODS: We used a cadaveric
      three-part proximal humeral osteotomy model to perform a biomechanical evaluation
      of three types of internal fixation devices: a cloverleaf plate, an angled blade
      plate, and Kirschner wires. The effect of supplementing the fixation with SRS
      (Skeletal Repair System) calcium phosphate cement was evaluated as well. Eighteen
      pairs of fresh-frozen humeri were obtained, and the bone-mineral density of each
      specimen was measured. In each pair, one specimen was secured with internal
      fixation alone and the contralateral specimen was secured with internal fixation
      combined with calcium phosphate cement. The specimens were tested cyclically in
      abduction and in external rotation for 250 cycles to evaluate interfragmentary
      motion. The specimens were then loaded to failure in external rotation to measure
      torsional load to failure and torsional stiffness. RESULTS: Overall, there were
      no significant differences between the specimens treated with the blade and
      cloverleaf plates, whereas the specimens treated with Kirschner wires
      demonstrated more interfragmentary motion, less stiffness, and lower torque to
      failure. In general, supplementation with calcium phosphate cement led to
      significant improvements in the mechanical performance of all three forms of
      internal fixation as demonstrated by a significant decrease in interfragmentary
      motion, a significant increase in torque to failure, and a significant increase
      in torsional stiffness. The addition of calcium phosphate cement increased the
      stiffness of even the most osteoporotic specimens to levels that were higher than
      those of the most osteodense specimens that had been treated with internal
      fixation alone. CONCLUSION: The initial biomechanical properties of internal
      fixation as measured with use of a proximal humeral osteotomy model and three
      methods of fixation were significantly improved by the addition of calcium
      phosphate cement.

PMID- 12063330
TI  - Isolated gastrocnemius tightness.
AB  - BACKGROUND: Contracture of the gastrocnemius-soleus complex has well-documented
      deleterious effects on lower-limb function in spastic or neurologically impaired
      individuals. There is scarce literature, however, on the existence of isolated
      gastrocnemius contracture or its impact in otherwise normal patients. We
      hypothesized that an inability to dorsiflex the ankle due to equinus contracture
      leads to increased pain in the forefoot and/or midfoot and therefore a population
      with such pain will have less maximum ankle dorsiflexion than controls. We
      further postulated that the difference would be present whether the knee was
      extended or flexed. METHODS: This investigation was a prospective comparison of
      maximal ankle dorsiflexion, as a proxy for gastrocnemius tension, in response to
      a load applied to the undersurface of the foot in two healthy age, weight, and
      sex-matched groups. The patient group comprised thirty-four consecutive patients
      with a diagnosis of metatarsalgia or related midfoot and/or forefoot symptoms.
      The control group consisted of thirty-four individuals without foot or ankle
      symptoms. The participants were clinically examined for gastrocnemius and soleus
      contracture and were subsequently assessed for tightness with use of a specially
      designed electrogoniometer. Measurements were made both with the knee extended
      (the gastrocnemius under tension) and with the knee flexed (the gastrocnemius
      relaxed). RESULTS: With the knee fully extended, the average maximal ankle
      dorsiflexion was 4.5 degrees in the patient group and 13.1 degrees in the control
      group (p < 0.001). With the knee flexed 90 degrees, the average was 17.9 degrees
      in the patient group and 22.3 degrees in the control population (p = 0.09). When
      gastrocnemius contracture was defined as dorsiflexion of < or = 5 degrees during
      knee extension, it was identified in 65% of the patients compared with 24% of the
      control population. However, when gastrocnemius contracture was defined as
      dorsiflexion of < or = 10 degrees, it was present in 88% and 44%, respectively.
      When gastrocnemius-soleus contracture was defined as dorsiflexion of < or = 10
      degrees with the knee in 90 degrees of flexion, it was identified in 29% of the
      patient group and 15% of the control group. CONCLUSIONS: On the average, patients
      with forefoot and/or midfoot symptoms had less maximum ankle dorsiflexion with
      the knee extended than did a control population without foot or ankle symptoms.
      When the knee was flexed 90 degrees to relax the gastrocnemius, this difference
      was no longer present. CLINICAL RELEVANCE: These findings support the existence
      of isolated gastrocnemius contracture in the development of forefoot and/or
      midfoot pathology in otherwise healthy people. These data may have implications
      for preventative and therapeutic care of patients with chronic foot problems.

PMID- 12063331
TI  - Long-term outcome after tibial shaft fracture: is malunion important?
AB  - BACKGROUND: Fractures of the shaft of the tibia often heal with some angulation.
      Although there is biomechanical evidence that such angulation alters load
      transmission through the joints of the lower limb, it is not clear whether it can
      eventually lead to osteoarthritis. METHODS: One hundred and sixty-four
      individuals who had sustained a tibial shaft fracture were assessed in a research
      clinic thirty to forty-three years after the injury. The subjects were evaluated
      with regard to self-reported lower limb joint pain, stiffness, and disability
      (assessed with the Western Ontario and McMaster Universities [WOMAC]
      osteoarthritis questionnaire); clinical signs of osteoarthritis; and radiographic
      evidence of osteophytes and joint-space narrowing in the knees, ankles, and
      subtalar joints. RESULTS: Twenty-two (15%) of the 151 subjects who reported no
      other knee injury reported at least moderate knee pain, and eight (6%) of the 145
      subjects who reported no other ankle injury reported at least moderate ankle
      pain. Seventeen (13%) of the 135 subjects who reported no other knee or ankle
      injury reported at least moderate disability. The ipsilateral side demonstrated a
      higher prevalence than the contralateral side in terms of pain with passive ankle
      movement (nineteen versus nine subjects, p = 0.02), pain with passive subtalar
      movement (fifteen versus four subjects, p = 0.01), and radiographic signs of
      ankle joint space narrowing (twelve subjects versus one subject, p = 0.0055).
      Knee osteoarthritis was frequently bilateral. Forty-seven fractures (29%) healed
      with coronal angulation of > or = 5 degrees. Apart from an association between
      shortening of > or = 10 mm and self-reported knee pain (p = 0.016), there were no
      significant univariate associations between these malunions and the development
      of osteoarthritis. Seventeen (15%) of 114 eligible subjects had overall
      malalignment of the lower limb, defined as a hip-knee-ankle angle outside the
      normal range of 6.25 degrees of varus to 4.75 degrees of valgus. This
      malalignment was due to the fracture malunion in nine subjects and predated the
      fracture in eight. In limbs with varus or valgus malalignment, there was an
      excess of subtalar stiffness (p = 0.04) and a nonsignificant trend toward more
      frequent knee pain. In limbs with varus malalignment, there was a nonsignificant
      trend toward more frequent radiographic evidence of osteoarthritis in the medial
      compartment of the knee joint. Most of the subjects in whom osteoarthritis was
      observed had normal overall alignment of the lower limb. CONCLUSIONS: The thirty
      year outcome after a tibial shaft fracture is usually good, although mild
      osteoarthritis is common. Fracture malunion is not the cause of the higher
      prevalence of symptomatic ankle and subtalar osteoarthritis on the side of the
      fracture. Although varus malalignment of the lower limb occurs occasionally and
      may cause osteoarthritis in the medial compartment of the knee, other factors are
      more important in causing osteoarthritis after a tibial shaft fracture.

PMID- 12063332
TI  - Results of arthroscopic treatment of superior labral lesions.
AB  - BACKGROUND: The purpose of this study was to evaluate the results of arthroscopic
      repair of isolated superior labral lesions of the shoulder. METHODS: We evaluated
      thirty-four patients at a mean of thirty-three months (range, twenty-four to
      forty-nine months) following arthroscopic repair of an isolated superior labral
      lesion of the shoulder with suture anchors. The outcome of treatment was
      evaluated with the University of California at Los Angeles shoulder score and on
      the basis of the patient's ability to return to prior activities. There were
      thirty male patients and four female patients with a mean age of twenty-six years
      (range, sixteen to thirty-five years). Thirty patients were involved in athletic
      activities, and eighteen of them were engaged in overhead sports. RESULTS: Repair
      of the superior labral lesion resulted in a satisfactory University of California
      at Los Angeles shoulder score for thirty-two patients (94%) and an unsatisfactory
      score for two. Thirty-one patients (91%) regained their preinjury level of
      shoulder function. The shoulder score and the return to activity were correlated
      with the type of sports activity (r = 0.291, p < 0.0001 and r = 0.373, p = 0.010,
      respectively. Patients participating in overhead sports had significantly lower
      shoulder scores and a lower percentage of return to their preinjury level of
      shoulder function compared with patients who were not engaged in overhead
      activity (p = 0.024 and 0.015, respectively). CONCLUSIONS: Arthroscopic repair of
      an isolated superior labral lesion is successful in a majority of patients.
      However, the results in patients who participate in overhead sports are not as
      satisfactory as those in patients who are not involved in overhead sports.

PMID- 12063333
TI  - Bone-lengthening for symbrachydactyly of the hand with the technique of callus
      distraction.
AB  - BACKGROUND: Bone-lengthening in the hand and foot is a relatively new application
      for distraction osteogenesis. We present the operative treatment and
      postoperative outcome for four patients with M ller type-D symbrachydactyly of
      the hand who underwent metacarpal lengthening with use of a distraction device to
      establish pinch function. METHODS: Four patients who underwent distraction
      osteogenesis for the treatment of congenital symbrachydactyly of the hand were
      evaluated over a thirteen-year period. The nondominant right hand was treated in
      two patients, and the nondominant left hand was treated in the other two. The
      patients included three boys and one girl; all patients had the operation between
      the ages of five and eleven years. Distraction osteogenesis was performed on the
      fifth metacarpal in one patient and on the fourth and fifth metacarpals in the
      remaining three, in whom both bones were lengthened simultaneously with use of a
      single device. Postoperative bone elongation was analyzed with radiographs made
      at the time of removal of the distractor. The sensory function of the treated
      fingers and any growth disturbance of the distracted bones were evaluated.
      RESULTS: The mean duration of distraction was 37.3 days (range, thirty-two to
      forty-nine days), and the distractor was removed at a mean of eighty-four days
      after surgery. The bones were lengthened by a mean of 22.3 mm (81.6% of their
      original length) at a rate of 0.6 mm/day. Pinch function was improved in all
      patients. CONCLUSIONS: On the basis of our limited experience, we found that
      distraction osteogenesis of the metacarpals was an effective technique for the
      establishment of pinch function. We also found that an intramedullary Kirschner
      wire could maintain the alignment of the osteotomized bone. Although distraction
      requires a longer treatment period, it is apparently more effective than bone
      grafting in terms of achieving adequate bone length. Simultaneous lengthening of
      two metacarpals also was found to be an effective technique.

PMID- 12063334
TI  - Surgical repair of acute traumatic closed transection of the biceps brachii.
AB  - BACKGROUND: Effective techniques to repair transected muscles are not well
      described. We determined the outcome of surgically repaired closed transections
      of the biceps muscle with regard to strength, appearance, and patient
      satisfaction. METHODS: We conducted a study on surgical repair of acute traumatic
      closed transection of the muscle belly of the biceps brachii in paratroopers.
      Muscle fibers and epimysium were sutured with use of running interlocked stitches
      as well as modified Mason-Allen stitches. We gathered data on the supination
      torque, appearance of the arm, and patient satisfaction. Nine patients underwent
      surgical repair and were followed for a mean of 2.2 years. Three patients, who
      constituted a comparative group, had nonoperative treatment of complete
      transections of the biceps and were followed for a mean of eleven years. RESULTS:
      We found that the patients who had surgical repair had better results than did
      those who had nonoperative treatment, with respect to supination torque (a mean
      of 11.0 N-m compared with 5.8 N-m, p = 0.0005), appearance (a mean of 4.6 cm
      compared with 3.0 cm, according to the cosmetic visual analog scale; p =
      0.000002), and satisfaction (excellent in all nine patients who had surgical
      repair and satisfactory in all three who had nonoperative treatment).
      CONCLUSIONS: The results after repair of acute traumatic closed transection of
      the biceps brachii with the new surgical technique described in the present study
      demonstrated a significant improvement in terms of function, appearance, and
      patient satisfaction compared with those after nonoperative treatment.

PMID- 12063335
TI  - Reconstruction of chronic ruptures of the distal biceps tendon with use of an
      achilles tendon allograft.
AB  - BACKGROUND: Chronic ruptures of the distal biceps tendon are uncommon and are
      complicated by the retraction and poor quality of the muscle and tendon. Surgical
      procedures that have been described for the treatment of this injury are limited
      by the quality and availability of the structures used for augmentation. The
      purpose of the present study was to describe the surgical technique for
      reconstruction of the tendon with an Achilles tendon allograft and to report our
      preliminary experience with this procedure. METHODS: An Achilles tendon allograft
      was used to reconstruct a chronic rupture of the distal biceps tendon in four
      patients. The patients were evaluated with regard to subjective satisfaction,
      pain, range of motion, and strength in flexion and supination. The results were
      graded with use of the Mayo elbow performance score. RESULTS: After an average
      duration of follow-up of 2.8 years (range, 2.0 to 3.7 years), all four patients
      had a satisfactory subjective result, a full range of motion, and an excellent
      Mayo elbow performance score. The strength of flexion and supination was
      comparable with that on the contralateral side in two patients and was slightly
      decreased in the other two. CONCLUSIONS: Reconstruction of chronic disruptions of
      the distal biceps tendon with an Achilles tendon allograft appears to offer a
      satisfactory technical solution for this challenging problem and has provided
      satisfactory clinical results to date.

PMID- 12063336
TI  - Treatment of partial lacerations in flexor tendons by trimming. A biomechanical
      in vitro study.
AB  - BACKGROUND: Treatment of a partial laceration in zone 2 of a flexor tendon is
      controversial. The intact part of the tendon can usually sustain forces of normal
      unresisted motion, and repaired partially lacerated tendons can actually be
      weaker than unrepaired ones. However, complications such as triggering or
      entrapment have been reported in association with unrepaired tendons. The purpose
      of this study was to measure the biomechanical behavior following trimming of the
      tendon as an alternative to repair. METHODS: Thirty-six flexor digitorum
      profundus tendons were harvested from sixteen unpaired fresh-frozen cadaveric
      human hands and were randomly assigned to be subjected to either 50% or 75%
      partial laceration, which was either lateral or volar, and were then assigned to
      no repair, repair with a running suture, or trimming. Mean and maximum gliding
      resistances were measured as the flexor digitorum profundus glided through the
      bone-A2 pulley complex and the flexor digitorum superficialis. Values were
      normalized to those measured in the intact tendon. The tendons were then
      distracted to failure, and maximum load and stiffness were recorded. RESULTS:
      There was triggering or entrapment of eight unrepaired tendons; two cases were
      severe, and six were minor. When no severe trigger was obvious, the unrepaired
      tendons had the lowest tendency for gliding resistance, followed by the tendons
      treated with trimming and then by those treated with the running suture. Overall,
      the tendons with a volar laceration had higher mean and maximum gliding
      resistance than those with a lateral laceration (p < 0.05), those with a 75%
      partial laceration had higher mean gliding resistance than those with a 50%
      laceration (p < 0.05), and the tendons that were repaired with running suture had
      higher mean gliding resistance than those treated with trimming (p < 0.05).
      Tendon strength was not significantly different among the three types of
      treatment. CONCLUSIONS: From the perspective of gliding resistance after partial
      tendon laceration, no repair appears necessary unless triggering is a problem. If
      triggering occurs, then trimming of a partially lacerated tendon may be a
      reliable alternative to repair, at least in terms of gliding resistance and
      strength.

PMID- 12063337
TI  - Anterior approach to the cervicothoracic junction by unilateral or bilateral
      manubriotomy. A report of five cases.

PMID- 12063338
TI  - Patella infera after nonoperative treatment of a patellar fracture. A case
      report.

PMID- 12063339
TI  - Tuberculous meningitis following correction of kyphosis by spinal osteotomy. A
      case report.

PMID- 12063340
TI  - An occult fracture of the trapezoid bone. A case report.

PMID- 12063341
TI  - Flexion-distraction injury of the upper thoracic spine associated with
      tracheoesophageal perforation. A case report.

PMID- 12063344
TI  - Having fun yet? A curmudgeon's view of career management.

PMID- 12063342
TI  - The role of growth factors in the repair of bone. Biology and clinical
      applications.

PMID- 12063345
TI  - Preoperative signing of the incision site in orthopaedic surgery in Canada.

PMID- 12063346
TI  - Orthopaedic recertification.
AB  - This report summarizes a symposium presented at the 2001 Annual Meeting of the
      American Orthopaedic Association that was designed to assess the current status
      of recertification by the American Board of Orthopaedic Surgery (ABOS) and to
      determine how it will change in the near future. Recertification is a process
      whereby the general public is assured of quality medical care by a competent and
      knowledgeable physician. As a professional organization, we have an obligation to
      provide quality care. The nature of the public demand for standards ensuring
      competence and the history of recertification in orthopaedic surgery are
      examined. The recertification of commercial airline pilots is reviewed, as it
      provides a model of an unrelated but highly skilled profession requiring
      intellectual and technical proficiency. The goals and plans of the American Board
      of Medical Specialties (ABMS), which encompasses the views of all twenty-four
      major specialty boards including orthopaedic surgery, are reviewed. Finally, the
      future plans of the ABOS for recertification are considered.

PMID- 12063347
TI  - Early or delayed surgical treatment of supracondylar humeral fractures in
      children.

PMID- 12063348
TI  - Statistical differences: consider the methodology.

PMID- 12063349
TI  - Classification system for adolescent idiopathic scoliosis.

PMID- 12063350
TI  - Coventry's classic.

PMID- 12063352
TI  - Soft-tissue injury in total knee arthroplasty.

PMID- 12063351
TI  - Routine pathological examination of surgical specimens from patients undergoing
      total hip and knee replacement.

PMID- 12063353
TI  - Orthopaedic surgery in the developing world--can orthopaedic residents help?

PMID- 12063354
TI  - What's new in sports medicine.

PMID- 12063356
TI  - The prevalence of eating disorders in female health care students.
AB  - Previous research has suggested a raised prevalence of eating disorders amongst
      female medical students. This study aimed to test the belief, commonly held by
      occupational physicians, that there is also an increased prevalence of eating
      disorders amongst female applicants to nurse training. If correct, it implies the
      need for additional support and may predict increased failure to complete the
      course. Three groups of female students were compared: applicants to a university
      nurse training course, first-year medical students and a comparison group of
      first-year university students on courses not related to health care. Possible
      eating disorders were identified using two self-report instruments, the EAT-26
      and the BITE questionnaires, and the body mass index. No significant statistical
      difference was found in the prevalence of eating disorders between the three
      groups, using the above measures. After controlling for age and ethnicity, 20% of
      the nurse applicants were found to have disordered eating patterns meriting
      further investigation, compared with 19% of medical students and 21% of arts
      students. The nursing students are being followed up to compare the progress of
      those with and without disordered eating patterns.

PMID- 12063357
TI  - The health of the workers in a rapidly developing country: effects of
      occupational exposure to noise and heat.
AB  - Occupational hygiene and safety have not been high on the agenda of industrial
      management in developing countries for a variety of reasons. This cross-sectional
      study was undertaken to assess the exposure to noise and heat, and to study the
      level of occupational hygiene practiced, at a foundry in a rapidly developing
      country (Dubai, United Arab Emirates). Audiometry, muscle cramps and visual
      acuity were measured in workers at a foundry and compared with the results from
      workers at a soft-drink bottling plant. Thermal stress, relative humidity,
      ventilation, illumination and noise levels were measured at different work units
      at the foundry and at the soft-drink bottling factory. Thermal stress index was
      high while relative humidity and ventilation were low at the foundry compared
      with the bottling plant. Noise levels were also high at the foundry, exceeding 90
      dB at almost all work units except the fabrication workshop. Mild or moderate
      visual defects were observed among 31% of foundry workers, compared with 19% of
      the bottling plant workers.Muscle cramps were reported by 30% of all workers at
      the foundry, compared with 5% at the bottling plant. Visual disability was the
      highest among furnace operators and fabricators. Mean hearing disability was 8.69
      +/- 1.08% among foundry workers, compared with 4.56 +/- 0.82% among bottling
      plant workers. The high thermal stress, noise levels and exposure to non-ionizing
      radiations at the foundry might have contributed to the higher frequency of
      muscle cramps and the greater hearing and visual disabilities, respectively,
      among these workers. Non-use of personal protective equipment and poor
      occupational hygiene and safety measures were also seen to affect eye and ear
      health adversely among the workers at the foundry.

PMID- 12063358
TI  - Health interventions for the metal working industry: which is the most cost
      effective? A study from a developing country.
AB  - This study ranked the cost-effectiveness of health interventions in the metal
      working industry in a developing country. Data were based on 82 034 workers of
      the Northern region of Mexico. Effectiveness was measured through 'healthy life
      years' (HeaLYs) gained. Costs were estimated per worker according to type and
      appropriate inputs from selected health interventions. 'Hand' was the anatomical
      region that yielded the most gain of HeaLYs and amputation was the injury that
      yielded the most gain of HeaLYs. The most effective health intervention
      corresponded to training, followed by medical care, education, helmets, safety
      shoes, lumbar supports, safety goggles, gloves and safety aprons. In dollar
      terms, education presented the best cost-effectiveness ratio (US$637) and safety
      aprons presented the worst cost-effectiveness ratio (US$1 147 770). Training
      proved to be a very expensive intervention, but presented the best effectiveness
      outcome and the second best cost-effectiveness ratio (US$2084). Cost
      effectiveness analyses in developing countries are critical. Corporations might
      not have the same funds and technology as those in developed countries or
      multinational companies.

PMID- 12063360
TI  - Dermal exposure assessment in occupational medicine.
AB  - The importance of dermal exposure has increased during the last few years, mainly
      because of the reduction of respiratory exposure to toxicants. Pesticides,
      aromatic amines and polycyclic aromatic hydrocarbons are considered to be the
      chemicals at highest dermal risk. In the occupational exposure limit lists of the
      American Conference of Governmental Industrial Hygienists (ACGIH) and of many
      countries, compounds that can be absorbed through the skin are identified by a
      skin notation. However, a generally accepted criterion for assigning skin
      notation does not exist. The recent attempts to develop health-based dermal
      occupational exposure limits (DOELs) have not been accepted, thus in practice
      their use has remained limited. To predict the systemic risk associated with
      dermal exposure and to enable agencies to set safety standards, penetration data
      are needed. Moreover, there is a need for a practical risk assessment model,
      particularly for small and medium-sized enterprises.

PMID- 12063361
TI  - Renal cell carcinoma and occupational exposure to chemicals in Canada.
AB  - This study assesses the effect of occupational exposure to specific chemicals on
      the risk of renal cell carcinoma in Canada. Mailed questionnaires were used to
      obtain data on 1279 (691 male and 588 female) newly diagnosed, histologically
      confirmed renal cell carcinoma cases and 5370 population controls in eight
      Canadian provinces, between 1994 and 1997. Data were collected on socio-economic
      status, smoking habit, alcohol use, diet, residential and occupational histories,
      and years of exposure to any of 17 chemicals. Odds ratios (ORs) and 95%
      confidence intervals (CIs) were derived using unconditional logistic regression.
      The study found an increased risk of renal cell carcinoma in males only, which
      was associated with occupational exposure to benzene; benzidine; coal tar, soot,
      pitch, creosote or asphalt; herbicides; mineral, cutting or lubricating oil;
      mustard gas; pesticides; and vinyl chloride. Compared with no exposure to the
      specific chemical, the adjusted ORs were 1.8 (95% CI = 1.2-2.6), 2.1 (1.3-3.6),
      1.4 (1.1-1.8), 1.6 (1.3-2.0), 1.3 (1.1-1.7), 4.6 (1.7-12.5), 1.8 (1.4-2.3) and
      2.0 (1.2-3.3), respectively; an elevated risk was also associated with exposure
      to cadmium salts and isopropyl oil. The risk of renal cell carcinoma increased
      with duration of exposure to benzene, benzidine, cadmium, herbicides and vinyl
      chloride. Very few females were exposed to specific chemicals in this study;
      further research is needed to clarify the association between occupational
      exposure to chemicals and renal cell carcinoma in females.

PMID- 12063359
TI  - Coal dust exposures in the longwall mines of New South Wales, Australia: a
      respiratory risk assessment.
AB  - This paper presents an analysis of personal respirable coal dust measurements
      recorded by the Joint Coal Board in the underground longwall mines of New South
      Wales from 1985 to 1999. A description of the longwall mining process is given.
      In the study, 11 829 measurements from 33 mines were analysed and the results
      given for each occupation, for seven occupational groups, for individual de
      identified mines and for each year of study. The mean respirable coal dust
      concentration for all jobs was 1.51 mg/m(3) (SD 1.08 mg/m(3)). Only 6.9% of the
      measurements exceeded the Australian exposure standard of 3 mg/m(3). Published
      exposure-response relationships were used to predict the prevalence of
      progressive massive fibrosis and the mean loss of FEV(1), after a working
      lifetime (40 years) of exposure to the mean observed concentration of 1.5
      mg/m(3). Prevalences of 1.3 and 2.9% were predicted, based on data from the UK
      and the USA, respectively. The mean loss of FEV(1) was estimated to be 73.7 ml.

PMID- 12063362
TI  - Innovative training posts.

PMID- 12063365
TI  - Smoking cessation.

PMID- 12063367
TI  - Preventing HIV infection in children.

PMID- 12063368
TI  - Cardiac resynchronization in chronic heart failure.
AB  - BACKGROUND: Previous studies have suggested that cardiac resynchronization
      achieved through atrial-synchronized biventricular pacing produces clinical
      benefits in patients with heart failure who have an intraventricular conduction
      delay. We conducted a double-blind trial to evaluate this therapeutic approach.
      METHODS: Four hundred fifty-three patients with moderate-to-severe symptoms of
      heart failure associated with an ejection fraction of 35 percent or less and a
      QRS interval of 130 msec or more were randomly assigned to a cardiac
      resynchronization group (228 patients) or to a control group (225 patients) for
      six months, while conventional therapy for heart failure was maintained. The
      primary end points were the New York Heart Association functional class, quality
      of life, and the distance walked in six minutes. RESULTS: As compared with the
      control group, patients assigned to cardiac resynchronization experienced an
      improvement in the distance walked in six minutes (+39 vs. +10 m, P=0.005),
      functional class (P<0.001), quality of life (-18.0 vs. -9.0 points, P= 0.001),
      time on the treadmill during exercise testing (+81 vs. +19 sec, P=0.001), and
      ejection fraction (+4.6 percent vs. -0.2 percent, P<0.001). In addition, fewer
      patients in the group assigned to cardiac resynchronization than control patients
      required hospitalization (8 percent vs. 15 percent) or intravenous medications (7
      percent vs. 15 percent) for the treatment of heart failure (P<0.05 for both
      comparisons). Implantation of the device was unsuccessful in 8 percent of
      patients and was complicated by refractory hypotension, bradycardia, or asystole
      in four patients (two of whom died) and by perforation of the coronary sinus
      requiring pericardiocentesis in two others. CONCLUSIONS: Cardiac
      resynchronization results in significant clinical improvement in patients who
      have moderate-to-severe heart failure and an intraventricular conduction delay.

PMID- 12063369
TI  - Ventricular pacing or dual-chamber pacing for sinus-node dysfunction.
AB  - BACKGROUND: Dual-chamber (atrioventricular) and single-chamber (ventricular)
      pacing are alternative treatment approaches for sinus-node dysfunction that
      causes clinically significant bradycardia. However, it is unknown which type of
      pacing results in the better outcome. METHODS: We randomly assigned a total of
      2010 patients with sinus-node dysfunction to dual-chamber pacing (1014 patients)
      or ventricular pacing (996 patients) and followed them for a median of 33.1
      months. The primary end point was death from any cause or nonfatal stroke.
      Secondary end points included the composite of death, stroke, or hospitalization
      for heart failure; atrial fibrillation; heart-failure score; the pacemaker
      syndrome; and the quality of life. RESULTS: The incidence of the primary end
      point did not differ significantly between the dual-chamber group (21.5 percent)
      and the ventricular-paced group (23.0 percent, P=0.48). In patients assigned to
      dual-chamber pacing, the risk of atrial fibrillation was lower (hazard ratio,
      0.79; 95 percent confidence interval, 0.66 to 0.94; P=0.008), and heart-failure
      scores were better (P<0.001). The differences in the rates of hospitalization for
      heart failure and of death, stroke, or hospitalization for heart failure were not
      significant in unadjusted analyses but became marginally significant in adjusted
      analyses. Dual-chamber pacing resulted in a small but measurable increase in the
      quality of life, as compared with ventricular pacing. CONCLUSIONS: In sinus-node
      dysfunction, dual-chamber pacing does not improve stroke-free survival, as
      compared with ventricular pacing. However, dual-chamber pacing reduces the risk
      of atrial fibrillation, reduces signs and symptoms of heart failure, and slightly
      improves the quality of life. Overall, dual-chamber pacing offers significant
      improvement as compared with ventricular pacing.

PMID- 12063370
TI  - Antiretroviral therapy during pregnancy and the risk of an adverse outcome.
AB  - BACKGROUND: Some studies suggest that combination antiretroviral therapy in
      pregnant women with human immunodeficiency virus type 1 (HIV-1) infection
      increases the risk of premature birth and other adverse outcomes of pregnancy.
      METHODS: We studied pregnant women with HIV-1 infection who were enrolled in
      seven clinical studies and delivered their infants from 1990 through 1998. The
      cohort comprised 2123 women who received antiretroviral therapy during pregnancy
      (monotherapy in 1590, combination therapy without protease inhibitors in 396, and
      combination therapy with protease inhibitors in 137) and 1143 women who did not
      receive antiretroviral therapy. RESULTS: After standardization for the CD4+ cell
      count and use or nonuse of tobacco, alcohol, and illicit drugs, the rate of
      premature delivery (<37 weeks of gestation) was similar among the women who
      received antiretroviral therapy and those who did not (16 percent and 17 percent,
      respectively); the rate of low birth weight (<2500 g) was 16 percent among the
      infants born to both groups; and the rate of very low birth weight (<1500 g) was
      2 percent for the group that received antiretroviral therapy and 1 percent for
      the group that did not. The rates of low Apgar scores (<7) and stillbirth were
      also similar or the same in the two groups. After adjustment for multiple risk
      factors, combination antiretroviral therapy was not associated with an increased
      risk of premature delivery as compared with monotherapy (odds ratio, 1.08; 95
      percent confidence interval, 0.71 to 1.62) or delivery of an infant with low
      birth weight (odds ratio, 1.03; 95 percent confidence interval, 0.64 to 1.63).
      Seven of the women who received combination therapy with protease inhibitors (5
      percent) had infants with very low birth weight, as compared with nine women who
      received combination therapy without protease inhibitors (2 percent) (adjusted
      odds ratio, 3.56; 95 percent confidence interval, 1.04 to 12.19). CONCLUSIONS: As
      compared with no antiretroviral therapy or monotherapy, combination therapy for
      HIV-1 infection in pregnant women is not associated with increased rates of
      premature delivery or with low birth weight, low Apgar scores, or stillbirth in
      their infants. The association between combination therapy with protease
      inhibitors and an increased risk of very low birth weight requires confirmation.

PMID- 12063371
TI  - Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections.
AB  - BACKGROUND: Patients with nasal carriage of Staphylococcus aureus have an
      increased risk of surgical-site infections caused by that organism. Treatment
      with mupirocin ointment can reduce the rate of nasal carriage and may prevent
      postoperative S. aureus infections. METHODS: We conducted a randomized, double
      blind, placebo-controlled trial to determine whether intranasal treatment with
      mupirocin reduces the rate of S. aureus infections at surgical sites and prevents
      other nosocomial infections. RESULTS: Of 4030 enrolled patients who underwent
      general, gynecologic, neurologic, or cardiothoracic surgery, 3864 were included
      in the intention-to-treat analysis. Overall, 2.3 percent of mupirocin recipients
      and 2.4 percent of placebo recipients had S. aureus infections at surgical sites.
      Of the 891 patients (23.1 percent of the 3864 who completed the study) who had S.
      aureus in their anterior nares, 444 received mupirocin and 447 received placebo.
      Among the patients with nasal carriage of S. aureus, 4.0 percent of those who
      received mupirocin had nosocomial S. aureus infections, as compared with 7.7
      percent of those who received placebo (odds ratio for infection, 0.49; 95 percent
      confidence interval, 0.25 to 0.92; P=0.02). CONCLUSIONS: Prophylactic intranasal
      application of mupirocin did not significantly reduce the rate of S. aureus
      surgical-site infections overall, but it did significantly decrease the rate of
      all nosocomial S. aureus infections among the patients who were S. aureus
      carriers.

PMID- 12063373
TI  - Management of human immunodeficiency virus infection in pregnancy.

PMID- 12063374
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 18-2002. A 48-year-old man with a cough and bloody sputum.

PMID- 12063375
TI  - Financial associations of authors.

PMID- 12063376
TI  - Cardiac-resynchronization therapy for heart failure.

PMID- 12063377
TI  - Mupirocin to prevent S. aureus infections.

PMID- 12063378
TI  - Supporting community efforts to assist orphans in Africa.

PMID- 12063379
TI  - Fecal DNA tests for colorectal cancer.

PMID- 12063380
TI  - Fluconazole prophylaxis against fungal infection in preterm infants.

PMID- 12063381
TI  - What vitamins should I be taking?

PMID- 12063382
TI  - Case 26-2001: scleroderma renal crisis and polymyositis.

PMID- 12063383
TI  - Pneumonia in children.

PMID- 12063384
TI  - Attorney General's intrusion into clinical practice.

PMID- 12063385
TI  - Conflicts of interest and libel action.

PMID- 12063386
TI  - IgG4 levels in non-Japanese patients with autoimmune sclerosing pancreatitis.

PMID- 12063387
TI  - Medicare's declining payments to physicians.

PMID- 12063388
TI  - Distribution of MLH1 foci on the synaptonemal complexes of chicken oocytes.
AB  - The frequency and distribution of the mismatch repair protein MLH1 was analyzed
      on synaptonemal complex spreads of chicken oocytes using indirect
      immunofluorescence. MLH1 foci appeared in late zygotene and their number remains
      constant throughout pachytene. The average number of foci on autosomal
      synaptonemal complexes (65.02 +/- 4.02) is in agreement with the number of
      chiasmata estimated from lampbrush chromosomes. The distribution of foci along
      the synaptonemal complexes is shown to be nonrandom and nonuniform in terms of
      the distances between them. It is concluded that MLH1 foci are good markers of
      crossing over in bird (chicken) meiocytes.

PMID- 12063389
TI  - Molecular cytogenetic analysis consistently identifies translocations involving
      chromosomes 1, 2 and 15 in five embryonal rhabdomyosarcoma cell lines and a PAX
      FOXO1A fusion gene negative alveolar rhabdomyosarcoma cell line.
AB  - Rhabdomyosarcoma in children is a "small round blue cell tumour" that displays
      skeletal muscle differentiation. Two main histological variants are recognised,
      alveolar (ARMS) and embryonal (ERMS) rhabdomyosarcoma. Whereas consistent
      chromosome translocations characteristic of ARMS have been reported, no such
      cytogenetic abnormality has yet been described in ERMS. We have used multiple
      colour chromosome painting to obtain composite karyotypes for five ERMS cell
      lines and one PAX-FOXO1A fusion gene negative ARMS. The cell lines were assessed
      by spectral karyotyping (SKY), tailored multi-fluorophore fluorescence in situ
      hybridisation (M-FISH) using series of seven colour paint sets generated to
      examine specific abnormalities, and comparative genomic hybridisation (CGH). This
      approach enabled us to obtain karyotypes of the cell lines in greater detail than
      previously possible. Several recurring cytogenetic abnormalities were
      demonstrated, including translocations involving chromosomes 1 and 15 and
      chromosomes 2 and 15, in 4/6 and 2/6 cell lines respectively. All six cell lines
      demonstrated abnormalities of chromosome 15. Translocations between chromosomes 1
      and 15 have previously been recorded in two primary cases of ERMS by conventional
      cytogenetics. Analysis of the translocation breakpoints may suggest mechanisms of
      ERMS tumourigenesis and may enable the development of novel approaches to the
      clinical management of this tumour.

PMID- 12063390
TI  - Microwave decondensation and codenaturation: a new methodology to maximize FISH
      data from donors with very low concentrations of sperm.
AB  - To increase analyzable sperm numbers when dealing with semen samples from donors
      with extremely low quantities of sperm, a microwave decondensation/codenaturation
      technique for fluorescence in situ hybridization (FISH) was developed and results
      were compared to those obtained from conventional FISH techniques. There was no
      significant difference between the frequencies of disomy and diploidy obtained
      using the two techniques.

PMID- 12063391
TI  - Localization, genomic organization, and alternative transcription of a novel
      human SAM-dependent methyltransferase gene on chromosome 2p22-->p21.
AB  - As part of our studies to identify the gene responsible for hereditary gingival
      fibromatosis, GINGF (OMIM 135300), we have identified and cloned a novel human
      gene that contains the highly conserved methyltransferase domain characteristic
      of S-adenosylmethionine-dependent methyltransferases. We localized this gene
      (C2orf8 encoding 288L6 SAM-methyltransferase) to chromosome 2p22-->p21 by FISH,
      and sublocalized it to BAC RP11 288L6 flanked by D2S2238 and D2S2331.
      Computational analysis of aligned ESTs identified ten exons in the hypothetical
      C2orf8 gene. Results of RACE analyses in placenta identified multiple transcripts
      of this gene with heterogeneity at the 5'-UTR. Alternative transcription and
      tissue specific expression of C2orf8 were detected by RT-PCR and Northern blot
      analyses. C2orf8 is expressed in a variety of tissues including brain, colon,
      gingiva, heart, kidney, liver, lung, placenta, small intestine, spleen, and
      thymus. Open reading frame analysis of the alternative transcripts identified a
      shared coding region spanning exons 6-10. This ORF consists of 732 nucleotides
      encoding a putative 244 amino acid protein. Bioinformational searches of both
      C2orf8 and the putative protein product identified three methyltransferase motifs
      conserved across many prokaryotic and eukaryotic species. Sequence analyses of
      C2orf8 excluded coding region mutations as causative of GINGF.

PMID- 12063392
TI  - A novel LPP fusion gene indicates the crucial role of truncated LPP proteins in
      lipomas and pulmonary chondroid hamartomas.
AB  - The lipoma preferred partner (LPP) gene is fused to the high mobility group
      protein gene HMGIC in lipomas and pulmonary chondroid hamartomas. In addition, a
      fusion of LPP to the mixed lineage leukemia (MLL) gene has been described in a
      case of acute myeloid leukemia. Herein, a novel LPP fusion transcript of LPP in a
      lipoma is described that points to the possible oncogenic potential of LPP.

PMID- 12063393
TI  - cDNA cloning, expression studies and chromosome mapping of human type I
      serine/threonine kinase receptor ALK7 (ACVR1C).
AB  - Transforming growth factor-beta (TGF-beta) superfamily related growth factors
      signal by binding to transmembrane type I and type II receptor serine/threonine
      kinases (RSTK), which phosphorylate intracellular Smad transcription factors in
      response to ligand binding. Here we describe the cloning of the human type I RSTK
      activin receptor-like kinase 7 (ALK7), an orthologue of the previously identified
      rat ALK7. Nodal, a TGF-beta member expressed during embryonic development and
      implicated in developmental events like mesoderm formation and left-right axis
      specification, was recently shown to signal through ALK7. We found ALK7 mRNA to
      be most abundantly expressed in human brain, pancreas and colon. A cDNA encoding
      the open reading frame of ALK7 was obtained from a human brain cDNA library.
      Furthermore, a P1 artificial chromosome (PAC) clone containing the human ALK7
      gene was isolated and fluorescent in situ hybridization (FISH) on metaphase
      chromosomes identified the gene locus as chromosome 2q24.1-->q3. To test the
      functionality of the ALK7 signaling, we generated recombinant adenoviruses
      containing a constitutively active form of ALK7 (Ad-caALK7), which is capable of
      activating downstream targets in a ligand independent manner. Infection with Ad
      caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be
      endogenously expressed, led to a marked increase in the phosphorylation of Smad2,
      a signaling molecule also used by TGF-betas and activins.

PMID- 12063394
TI  - Genomic organization of the DCTN1-SLC4A5 locus encoding both NBC4 and
      p150(Glued).
AB  - In eukaryotes, it is rare for a single gene to encode two functionally unrelated
      proteins. p150(Glued) is a component of the dynactin heteromultimeric complex of
      proteins which is required for dynein-mediated vesicle and organelle transport by
      microtubules. NBC4 is an electrogenic sodium bicarbonate cotransporter, which
      regulates intracellular pH. Here we report that NBC4 and p150(Glued) are encoded
      by the same locus, DCTN1-SLC4A5. We have characterized the genomic organization
      of the human DCTN1-SLC4A5 locus which spans approximately 230 kilobases on
      chromosome 2p13 and contains 66 exons. This information should allow the study of
      potential genomic alterations of DCTN1-SLC4A5 in patients with diseases mapping
      to this genomic region.

PMID- 12063396
TI  - Molecular cloning and characterization of the human NIMA-related protein kinase 3
      gene (NEK3).
AB  - NEKs (NIMA-related kinases) are a group of protein kinases sharing high amino
      acid sequence identities with NIMA (never in mitosis gene a) which control
      mitosis in Aspergillus nidulans. We have cloned a cDNA for human NEK3, a novel
      human gene structurally related to NIMA, by RT-PCR. Its open reading frame
      encodes a protein of 489 amino acid residues with the calculated molecular mass
      of 56.0 kDa and a predicted pI of 6.58. Phylogenetic analysis suggests that mouse
      and human NEK3s constitute a subfamily within the NIMA family of protein kinases.
      The expression pattern of NEK3 was studied by RT-PCR and a high level of
      expression was detected in testis, ovary, and brain, with low-level expression
      being detected in most of the tissues studied. NEK3 mRNA was detected in all the
      proliferating cell lines studied, and the amount did not change during the cell
      cycle. The human NEK3 gene was assigned to human chromosome 13 by somatic cell
      hybrids and 13q14.2 by radiation hybrid mapping.

PMID- 12063395
TI  - Conservation of RET proto-oncogene splicing variants and implications for RET
      isoform function.
AB  - The RET proto-oncogene encodes a receptor tyrosine kinase required for
      development of the kidney and neural crest-derived cell types. Alternative
      splicing of the 3' exons of human RET results in three protein isoforms with
      distinct C-termini: RET9, RET51, and RET43. These RET isoforms show differential
      binding to downstream adapter molecules, suggesting they may have distinct
      signaling functions. We have characterized Ret 3' sequences in mouse and
      investigated alternative splicing of this region. We found that the organization
      of Ret 3' sequences is very similar to human RET. The mouse locus also has
      alternatively spliced C-terminal coding regions, and the sequences corresponding
      to RET9 and RET51 are highly conserved in both position and sequence with the
      human locus. Further, we compared the predicted C-terminal amino acids of RET9
      and RET51 in seven vertebrate species, and found that they are well conserved. We
      have identified sequence encoding a putative ret43 isoform in mouse, however the
      predicted amino acid sequence showed low homology to human RET43. Our data
      suggest that RET isoforms are evolutionarily highly conserved over a broad range
      of species, which may indicate that each isoform has a distinct role in normal
      RET function.

PMID- 12063397
TI  - Identification and molecular characterization of de novo translocation
      t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a disorder primarily characterized by
      capillary-venous vascular malformations associated with altered limb bulk and/or
      length. We report the identification of a balanced translocation involving
      chromosomes 8q22.3 and 14q13 in a patient with a vascular and tissue overgrowth
      syndrome consistent with KTS. We demonstrated that translocation
      t(8;14)(q22.3;q13) arose de novo. These data suggest that a pathogenic gene for a
      vascular and tissue overgrowth syndrome (KTS) may be located at chromosome 8q22.3
      or 14q13. Fluorescence in situ hybridization (FISH) analysis was used to define
      the breakpoint on chromosome 8q22.3 to a <5-cM interval flanked by markers
      AFMA082TG9 and GATA25E10, and the 14q13 breakpoint within a 1-cM region between
      STSs WI-6583 and D14S989. This study provides a framework for the fine-mapping
      and ultimate cloning of a novel vascular gene at 8q22.3 or 14q13.

PMID- 12063398
TI  - Molecular cytogenetic investigations define a subgroup of thyroid adenomas with
      2p21 breakpoints clustered to a region of less than 450 kb.
AB  - Structural rearrangements involving chromosome band 2p21 characterize a
      cytogenetic subgroup of benign thyroid tumors. To narrow down the breakpoints of
      these aberrations, we established two cell lines from benign thyroid tumors
      showing translocations involving 2p21. These two cell lines and one additional
      primary tumor were used for FISH-studies with 18 BAC clones. All breakpoints were
      mapped to a cluster of about 450 kb.

PMID- 12063399
TI  - Comparative mapping of five coding DNA sequences on cattle chromosomes 7 and 25.
AB  - Comparative mapping of four genes and one unknown coding DNA sequence in
      breakpoint positions of bovine chromosomes (BTA) 7 and 25 are presented.
      Performing a genome data base search five bovine expressed sequence tags from the
      MARC library matched with human genes coding for the general transcription factor
      IIIC polypeptide 1 (GTF3C1), the hypothetical protein KIAA0556, the interleukin 4
      receptor (IL4R), the regulatory factor X-associated ankyrin-containing protein
      (RFXANK), and with an unknown human coding sequence partially homologous to the
      genomic cosmid clone R30923. Loci for these sequences were COMPASS predicted on
      BTA7 or BTA18 and to BTA18 or BTA25. Mapping was performed in a cattle-hamster
      somatic hybrid cell panel and a cattle-hamster 5000 rad whole genome radiation
      hybrid panel. GTF3C1, KIAA0556 and IL4R were assigned to the centromere region of
      BTA25 and RFXANK and R30923 close to the centromere of BTA7. The assignments
      contribute to the identification of evolutionary chromosome break points between
      human chromosomes 16 and 19 and BTA7, BTA18, and BTA25.

PMID- 12063400
TI  - The mouse Arhgef6 gene: cDNA sequence, expression analysis, and chromosome
      assignment.
AB  - Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho
      GTPases, have been shown to cause X-chromosomal non-specific mental retardation
      (MRX) in human. Here we report the identification and characterization of the
      orthologous mouse gene, Arhgef6. The gene transcript of approximately 4.4 kb is
      present in various mouse tissues indicating ubiquitous expression as found for
      human ARHGEF6. The open reading frame encodes a polypeptide of 771 amino acids
      with high homology to human ARHGEF6. The structural motifs of both proteins are
      conserved including an N-terminal CH domain, followed by an SH3 domain, and a
      tandem organization of the DH and PH domains. Analysis of the temporal expression
      pattern revealed that Arhgef6 is strongly expressed in the very early embryo and
      somewhat less in later stages. A genomic cosmid clone containing Arhgef6 exons 1
      and 2 has been isolated and used for mapping the gene on the mouse X chromosome.

PMID- 12063401
TI  - Analysis of chromosomal aberrations involving chromosome 1q31-->q53 in a DMBA
      induced rat fibrosarcoma cell line: amplification and overexpression of Jak2.
AB  - In a study of DMBA-induced rat fibrosarcomas we repeatedly found deletions and/or
      amplifications in the long arm of rat chromosome 1 (RNO1). Comparative genome
      hybridization showed that there was amplification involving RNO1q31-->q53 in one
      of the DMBA-induced rat fibrosarcoma tumors (LB31) and a cell culture derived
      from it. To identify the amplified genes we physically mapped rat genes
      implicated in cancer and analyzed them for signs of amplification. The genes were
      selected based on their locations in comparative maps between rat and man. The
      rat proto-oncogenes Ccnd1, Fgf4, and Fgf3 (HSA11q13.3), were mapped to RNO1q43 by
      fluorescence in situ hybridization (FISH). The Ems1 gene was mapped by radiation
      hybrid (RH) mapping to the same rat chromosome region and shown to be situated
      centromeric to Ccnd1 and Fgf4. In addition, the proto-oncogenes Hras (HSA11p15.5)
      and Igf1r (HSA15q25-->q26) were mapped to RNO1q43 and RNO1q32 by FISH and Omp
      (HSA11q13.5) was assigned to RNO1q34. PCR probes for the above genes together
      with PCR probes for the previously mapped rat genes Bax (RNO1q31) and Jak2
      (RNO1q51-->q53) were analyzed for signs of amplification by Southern blot
      hybridization. Low copy number increases of the Omp and Jak2 genes were detected
      in the LB31 cell culture. Dual color FISH analysis of tumor cells confirmed that
      chromosome regions containing Omp and Jak2 were amplified and were situated in
      long marker chromosomes showing an aberrant banding pattern. The configuration of
      the signals in the marker chromosomes suggested that they had arisen by a break
      fusion-bridge (BFB) mechanism.

PMID- 12063402
TI  - The pattern of phylogenomic evolution of the Canidae.
AB  - Canidae species fall into two categories with respect to their chromosome
      composition: those with high numbered largely acrocentric karyotypes and others
      with a low numbered principally metacentric karyotype. Those species with low
      numbered metacentric karyotypes are derived from multiple independent fusions of
      chromosome segments found as acrocentric chromosomes in the high numbered
      species. Extensive chromosome homology is apparent among acrocentric chromosome
      arms within Canidae species; however, little chromosome arm homology exists
      between Canidae species and those from other Carnivore families. Here we use Zoo
      FISH (fluorescent in situ hybridization, also called chromosomal painting) probes
      from flow-sorted chromosomes of the Japanese raccoon dog (Nyctereutes
      procyonoides) to examine two phylogenetically divergent canids, the arctic fox
      (Alopex lagopus) and the crab-eating fox (Cerdocyon thous). The results affirm
      intra-canid chromosome homologies, also implicated by G-banding. In addition,
      painting probes from domestic cat (Felis catus), representative of the ancestral
      carnivore karyotype (ACK), and giant panda (Ailuropoda melanoleuca) were used to
      define primitive homologous segments apparent between canids and other carnivore
      families. Canid chromosomes seem unique among carnivores in that many canid
      chromosome arms are mosaics of two to four homology segments of the ACK
      chromosome arms. The mosaic pattern apparently preceded the divergence of modern
      canid species since conserved homology segments among different canid species are
      common, even though those segments are rearranged relative to the ancestral
      carnivore genome arrangement. The results indicate an ancestral episode of
      extensive centric fission leading to an ancestral canid genome organization that
      was subsequently reorganized by multiple chromosome fusion events in some but not
      all Canidae lineages.

PMID- 12063403
TI  - A case of azoospermia in a bull carrying a Y-autosome reciprocal translocation.
AB  - During normal cytogenetic investigations on the Chianina cattle (BTA) breed, a
      normal looking young bull was found to carry an abnormal Y chromosome which was a
      product of a reciprocal translocation between chromosomes Y and 9. This was
      revealed by both CBA- and RBG-banding techniques and was clearly confirmed by
      FISH-mapping analysis with IDVGA50 (which paints the complete Yq arm in a normal
      Y), as well as with AMD1, CGA, IGF2R (mapping to BTA9q16, BTA9q22 and BTA9q27-
      >q28, respectively) and SRY (mapping to normal BTAYq23). Analysis on sperm from
      four different samples revealed azoospermia in the carrier, indicating that the
      rcp(Y;9) induces sterility in the bull.

PMID- 12063404
TI  - Trisomy 17 in a bonobo (Pan paniscus) and deletion of 3q in a lowland gorilla
      (Gorilla gorilla gorilla): comparison with human trisomy 18 and human deletion 4q
      syndrome.
AB  - A female bonobo (Pan paniscus) born at the San Diego Zoo exhibited inability to
      nurse and progressive weakness plus multiple congenital abnormalities including
      aural canal atresia and stenosis, malformed auricles, clenched hands, lordosis,
      agenesis of the caudal vertebra and cardiac abnormalities. Chromosome analysis
      identified the bonobo as being trisomic for chromosome 17, the homolog of human
      chromosome 18. Genotyping with human microsatellites suggested the extra
      chromosome was maternal in origin. In addition, a male lowland gorilla (Gorilla
      gorilla gorilla), also born at the zoo, exhibited postnatal growth retardation,
      facial dysmorphisms and small hands with short fingers. Karyotype analysis
      revealed the gorilla carried a deletion of the distal q arm of chromosome 3, the
      homolog of human chromosome 4. The phenotypic and karyotypic abnormalities found
      in the bonobo and gorilla were consistent with the characteristics of human
      trisomy 18 and human deletion 4q syndrome, respectively.

PMID- 12063405
TI  - Assignment of panopsin (OPN3) to human chromosome band 1q43 by in situ
      hybridization and somatic cell hybrids.

PMID- 12063406
TI  - Assignment of progesterone receptor (PGR) to canine chromosome band 21q1.2 by in
      situ hybridization.

PMID- 12063407
TI  - Assignment of GRINL1B, a glutamate receptor-like processed gene, to human
      chromosome 4q12 by in situ hybridization.

PMID- 12063408
TI  - The mouse orthologue of the human ionotropic glutamate receptor-like gene
      (GRINL1A) maps(1) to mouse chromosome 9.

PMID- 12063409
TI  - Assignment of the mouse Vegfb gene to mouse chromosome 19 B by in situ
      hybridization.

PMID- 12063410
TI  - Assignment of the mouse Pcolce2 gene, which encodes procollagen C-proteinase
      enhancer protein 2, to chromosome 9 and localization of PCOLCE2 to human
      chromosome 3q23.

PMID- 12063411
TI  - New paradigm for health disparities needed.

PMID- 12063412
TI  - Racial and socioeconomic differences in risk factors for cardiovascular disease
      among Southern rural women.
AB  - BACKGROUND: African American women living in the Southeast experience a higher
      mortality due to cardiovascular (CV) disease than their White counterparts. It is
      unclear if this vulnerability to CV disease is due to race, socioeconomic status,
      or health behaviors. OBJECTIVES: To examine the disparities in cardiovascular
      health between Southern rural, African American and White women to determine if a
      CV Risk-Index differed by race, education, or income levels and if differences
      persisted when controlling for body mass index (BMI). METHODS: Subjects were
      1,110 women (27% African American, 73% White) residing in rural North Carolina.
      Data were collected by mailed questionnaire and analyzed using analysis of
      variance (ANOVA) and analysis of covariance (ANCOVA). RESULTS: African American
      women had significantly lower education and lower income than Whites, higher BMI,
      and a much greater prevalence of hypertension, angina, and diabetes. In a three
      way ANOVA including race, income, and education, education and race were
      significant predictors of the CV Risk Index, but when adjusted for BMI race was
      no longer significant (p =.3039); the only significant predictors were BMI and
      educational level. DISCUSSION: Women with the least education had the highest CV
      Risk-Index, regardless of race. These findings suggest the need to focus risk
      reduction interventions on all Southern rural women with limited education, not
      only African American women. This supports the current literature that suggests
      race should be viewed as a risk marker rather than a risk factor.

PMID- 12063413
TI  - Racial differences in the use of cardiac procedures in patients with acute
      myocardial infarction.
AB  - BACKGROUND: Although numerous studies have shown that Black patients are less
      likely than White patients to undergo cardiac procedures, most of these studies
      did not consider clinical and demographic factors that could account for observed
      racial differences. OBJECTIVE: To determine if there are racial differences in
      the use of coronary angiography and revascularization procedures in patients with
      acute myocardial infarction, while controlling for multiple potentially important
      demographic and clinical variables. METHODS: In this retrospective cohort study,
      data were obtained from medical records of 642 consecutive Black and White
      patients with acute myocardial infarction at a regional cardiac referral center
      in southern New England. RESULTS: Blacks were significantly less likely than
      Whites to undergo angiography (p =.004; adjusted odds ratio =.36; 95% confidence
      interval =.18 -.72) and revascularization procedures (p =.006; adjusted odds
      ratio =.21; 95% confidence interval =.07 -.64). In the subgroup admitted directly
      to the hospital (n = 465), rather than transferred in from outlying hospitals,
      there were no racial differences in the use of angiography, but Blacks were
      significantly less likely to undergo revascularization procedures (p =.004;
      adjusted odds ratio =.18; 95% confidence interval =.06 -.58). CONCLUSIONS: In
      patients hospitalized with acute myocardial infarction, there are substantial
      racial differences in the use of angiography and revascularization procedures
      that cannot be explained by clinical or demographic factors.

PMID- 12063414
TI  - Relationships between psychosocial factors and abusive parenting attitudes in low
      income single mothers.
AB  - BACKGROUND: Linkages among family violence, maternal mental health, and parenting
      attitudes are not clearly understood. OBJECTIVE: To investigate the relationships
      of abuse (childhood and/or partner), everyday stressors, self-esteem, depressive
      symptoms, and anger with abusive parenting attitudes. METHOD: Cross-sectional
      analysis of data collected in interviews with 53 low-income, single mothers from
      wave two of a 3-wave study. A conceptual framework and bivariate correlations
      guided a series of multiple regressions to identify the best predictors for each
      variable. RESULTS: A high prevalence of abuse, depressive symptoms, and abusive
      parenting attitudes was found. Few women had ever received mental health
      treatment. Abuse (partner and childhood physical) predicted higher everyday
      stressors which in turn predicted lower self-esteem. Childhood abuse and lower
      self-esteem predicted more depressive symptoms. More depressive symptoms were
      related to higher levels of state anger. More everyday stressors and more
      depressive symptoms predicted higher levels of trait anger. Higher levels of
      anger expression were associated with higher everyday stressors and lower self
      esteem. The presence of partner abuse best predicted higher levels of overall
      abusive parenting attitudes and more parent-child role reversal. Less parental
      empathy was associated with higher levels of state anger. CONCLUSIONS: This study
      partially explains the relationships of maternal abuse history and mental health
      status with parenting attitudes. Other predictors of parenting attitudes remain
      to be identified. The findings underscore the need for healthcare providers to
      consider the mental health status and abuse histories of low-income, single
      mothers. The potential disturbance in the parenting process of single mothers in
      abusive relationships warrants further investigation.

PMID- 12063415
TI  - Planning a sexual health promotion intervention with homeless adolescents.
AB  - BACKGROUND: Homeless adolescents are at very high risk for sexually transmitted
      diseases (STDs), but few street-based interventions have been developed, tested,
      and made available to reduce risk and promote sexual health within this growing
      population. OBJECTIVES: This study, part of a larger study of the sexual health
      practices of homeless adolescents, explores participants' perceived need for more
      knowledge about sexual health and their ideas about developing a brief
      intervention to promote positive sexual health practices that would reflect their
      perspective. METHODS: Four focus groups with five to six participants each were
      conducted with 22 youth aged 16-20 years, randomly selected from the study sample
      of 425 homeless youth. Most participants (82%) were White, one was American
      Indian, two were Hispanic, and one did not indicate ethnicity. Local groups were
      audiotape recorded, transcribed, and analyzed for manifest and latent content.
      RESULTS: Participants were knowledgeable about symptoms, transmission,
      prevention, and treatment of STDs, but perceived the need for more knowledge
      about types of hepatitis, cancer, and long-term sequelae of untreated STDs.
      Participants identified barriers to seeking diagnosis and treatment for symptoms
      of STDs including cost, not knowing where to go, and lack of services
      specifically for females. They suggested developing a sexual health intervention
      based on respect that would provide concrete examples of how to promote their
      sexual health. CONCLUSIONS: Homeless adolescents were generally knowledgeable
      about symptoms and prevention of STDs and thought that street outreach
      interventions should be (a) brief, (b) gender-specific, (c) focused on the unique
      vulnerabilities and strengths of homeless youth, and (d) accessible.

PMID- 12063416
TI  - Strengths and vulnerabilities of women of Mexican descent in relation to
      depressive symptoms.
AB  - BACKGROUND: The majority of research related to depression among women of Mexican
      descent has focused on risk factors and resources without considering intrinsic
      strength factors that may have a protective function. An additional focus on
      mastery, resilience, and life satisfaction will expand the context for
      understanding the mental health of women of Mexican descent. OBJECTIVES: This
      study describes the level of depressive symptoms experienced by low-income women
      of Mexican descent living in an urban community in northern California and
      compares the level of symptoms by exposure to the United States (US) during
      childhood. Rather than focus only on negative demographic characteristics (such
      as lower socioeconomic status) associated with high levels of depressive
      symptoms, this study also focused on strengths and resources that may minimize or
      modify depressive symptoms. METHODS: Questionnaires were completed by a cross
      sectional convenience sample of 315 women of Mexican descent, aged 21-40 years.
      Data were analyzed using descriptive statistics and multiple regression. RESULTS:
      Women who spent all of their childhood years in Mexico before coming to the US
      had a lower level of depressive symptoms (p <.05) and more satisfaction with life
      than women who were exposed to the US in childhood (p =.001). While income,
      adequacy of financial resources, partner status, alcohol use, and childhood
      exposure to the US accounted for 13% of the variance in depressive symptoms,
      intrinsic strength factors such as mastery, life satisfaction, and resilience
      accounted for an additional 31% of the variance (p <.001). DISCUSSION: Although
      intrinsic strength factors have rarely been included in research related to
      depression in women of Mexican descent, they were more directly related to lack
      of depressive symptoms than traditional demographic risk factors.

PMID- 12063417
TI  - African American girls' smoking habits and day-to-day experiences with racial
      discrimination.
AB  - BACKGROUND: Although it is recognized that African Americans experience racial
      discrimination, relatively little research has explored the health implications
      of this experience. Few studies have examined the relationship between racial
      discrimination and specific health risks. OBJECTIVES: To examine the relationship
      between smoking habits and perceptions of racial discrimination among African
      American adolescent girls and to identify and test potential psychological
      mechanisms through which racial discrimination may operate to increase smoking
      among this group. METHODS: A sample of 105 African American adolescent girls
      (mean age 15.45 years) derived from a larger cross-sectional research project
      comprised the sample. Univariate analyses were conducted to provide descriptive
      data on the participants of the study, including information about their use of
      licit and illicit substances. Bivariate correlational analyses were conducted to
      evaluate the relationship between perceptions of discrimination and smoking
      habits. The ability of stress to mediate the relationship between discrimination
      and smoking was examined by using standard analytical procedures for testing
      mediation models as outlined by Baron and Kenny (1986). RESULTS: The sample (93%)
      reported experiencing discrimination and racial discrimination was highly
      correlated with cigarette smoking (r =.35, p >.001). Removing the effects of
      stress significantly reduced the relationship between racial discrimination and
      smoking (r =.17, p <.05), indicating that racial discrimination is related to
      smoking because of its stressful nature. CONCLUSION: Perceptions of racial
      discrimination are related to the smoking habits of African American adolescent
      girls.

PMID- 12063418
TI  - Clinical outcomes for low-income adults with hypertension and diabetes.
AB  - BACKGROUND: Long-term management of hypertension and diabetes, which are more
      prevalent in minority and socioeconomically disadvantaged populations, presents
      challenges for healthcare providers in community health centers. OBJECTIVES: The
      purpose of the study was twofold: to examine health outcomes for persons with
      hypertension and diabetes and to compare these outcomes for disparities in
      patients who were Black, Hispanic, or White. METHODS: Medical records (N = 280)
      from an urban community health center that serves predominantly uninsured adults
      were reviewed for selected clinical outcomes of primary care. Measures included
      outcomes of hypertension and diabetes control, lifestyle behaviors, preventive
      care, and patient status. Chi-square tests, t tests, and one-way analysis of
      covariance were used to analyze racial/ethnic group differences. RESULTS: Data
      revealed significant differences in smoking status, influenza immunization, and
      blood pressure. Racial/ethnic group differences were minimal compared with the
      overall high prevalence of risk factors such as smoking and obesity. Regular
      access to primary care did not result in improved clinical outcomes. CONCLUSION:
      The findings support the need for more effective interventions that promote
      healthy lifestyle if health disparities in low-income populations with chronic
      conditions are to be reduced.

PMID- 12063419
TI  - Burden on family members: caring for frail elderly: a meta-analysis of
      interventions.
AB  - BACKGROUND: Although multiple interventional approaches to reduce perceived
      burden among caregivers of the frail elderly have been investigated for over a
      decade, the effectiveness of those interventions and the benefits of group versus
      individual interventions are largely unclear. OBJECTIVES: This meta-analysis was
      undertaken to (a) assess the effectiveness of group and individual interventions
      on decreasing burden of caregivers of the frail elderly, and (b) identify factors
      with potential influence on the magnitude of the effects. METHOD: Computerized
      literature searches and manual searches of published true and quasi-experimental
      studies with control groups were performed. A coding form was developed to record
      methodological and other study characteristics, including study design, attrition
      rate, and reliability and validity of the measures. RESULTS: Eighteen group and
      eight individual interventional studies published from 1985 to 2000 were
      included. For group interventions, the sample size for individual studies ranged
      from 20 to 486, with a total of 1,970. The weighted mean effect size was 0.41
      (95% CI: 0.32 to 0.51), indicating a significant positive treatment effect. A
      significant homogeneity test (Q(17) = 56.37, p <.0001) indicated that there were
      variations in effect sizes among the studies attributable to study
      characteristics. The effect size in the 11 true experimental studies was smaller
      (M: 0.26, 95% CI: 0.15 to 0.37) but still existed. For individual interventions,
      the sample sizes ranged from 16 to 168, with a total of 472. The weighted effect
      sizes were homogeneous with a mean of 0.48 (95% CI: 0.30 to 0.67), indicating a
      positive treatment effect. DISCUSSION: Available evidence supports the premise
      that both group and individual interventions reduce perceived burden, however,
      this evidence is inconclusive. Further studies of large scale and high quality
      designs are needed.

PMID- 12063420
TI  - [Pregnancy and medical radiation: to demystify and take the drama out of
      managing].

PMID- 12063421
TI  - [Elias A. Zerhouni: a radiologist head of the NIH].

PMID- 12063422
TI  - [Sonographic imaging of lymphatic vessels compared to other methods].
AB  - This paper reviews for the first time the normal and abnormal appearances of
      lymphatic channels of the skin using ultrasound. After a review of anatomy and
      histology, the authors present the current imaging modalities available for lymph
      vessel imaging. The ultrasound examination is presented with a description of the
      author's technique as well as the technical requirements of the ultrasound unit
      (12 MHz linear probe with a resolution of 400 microns). They present the
      ultrasound appearance of normal lymphatic channels and their relationships to the
      dermis, hypodermis and lymph nodes, and at last the ultrasound appearance of
      abnormal lymphatic pathways

PMID- 12063423
TI  - [Sinusoidal abnormalities of the liver: MR imaging features].
AB  - This article reviews the different MR features found in sinusoidal lesions of the
      liver parenchyma. The diagnosis of these abnormalities is mainly based on the
      pathologic examination. These diagnoses relate to numerous diseases including
      veno-occlusive disease, Budd-Chiari disease, peliosis, hepato-portal sclerosis,
      and portal intra-sinusoidal thrombosis. The use of fast multi-slice acquisitions
      associated with dynamic enhancement of the liver leads to an efficient
      examination and allows analysis of both the parenchymal and vascular components
      of the liver.

PMID- 12063424
TI  - [To improve the quality of requisitions for radiologic examinations].
AB  - PURPOSE: This article presents the different steps implemented in order to
      improve the quality of requisitions for radiologic examinations in a hospital.
      MATERIAL: and methods. The radiology requests sent from clinical units are
      periodically analyzed using criteria about tracking, prescription and security
      required for a good examination. Results are discussed with the clinical units in
      order to achieve improvements. RESULTS: The periodical analysis of
      nonconformities shows a gradual improvement of practices. This action contributes
      to the realization of a single document for every request of examination or
      analysis in the hospital. CONCLUSION: The described action is in the context of
      French regulations, first about the practice of radiology, second about the
      obligation of quality improvement that health care facilities now have to
      implement for their accreditation.

PMID- 12063425
TI  - [Dual energy x-ray absorptiometry assessment of the bone mineral content and body
      composition during growth].
AB  - PURPOSE: To propose a simple method of analysis of whole body DXA scan results,
      for the bone mineral content of the entire skeleton (BMCt) and the arms and legs
      (BMCa and BMCl), as well as the analysis of the body composition in lean (Lt, La
      and Ll) and fat (Ft, Fa and Fl) in children and adolescents with normal growth.
      Materials and methods. A whole body DXA scan (Norland XR36(TM) DXA system) was
      performed in 90 control females and 76 control males aged from 2.3 y to 21.0 y,
      and from 2.3 y to 20.1 y, respectively. BMC values, as well as L and F values
      were correlated with the body weight (BW) of the measured subjects. BMCt, Lt and
      Ft values corrected for the body surface area (BS), and the ratio BMCl/BMCa, were
      also calculated. RESULTS: High linear correlations (r>0.9) were found between
      BMCt, Lt or Ft values and BW, as well as between BMC (a & l) and BMCt, L (a & l)
      and Lt, F (a & l) and Ft. The ratios BMCt/BS(1.5), Lt/BS(1.5), and Ft/BS(1.5) had
      constant values of 1.2+/-0.1, 17.5+/-1.9, and 8.7+/-2.0, respectively, in
      females, and 1.2+/-0.1, 18.9+/-1.3, and 7.3+/-1.4, in males. The ratio BMCl/BMCa
      had a constant value of 2.8+/-0.4 in both sexes. CONCLUSION: The reference values
      obtained by DXA for the bone mineral content, lean and fat masses of the entire
      body and limbs are of interest, in our experience, to follow-up the growth in
      patients with long-term treatments, and to quantify orthopedic disorders and
      treatments.

PMID- 12063426
TI  - [Contribution of spiral CT for the early diagnosis of hepato-cellular carcinoma
      in cirrhotic patients].
AB  - PURPOSE: To evaluate the specificity of spiral CT for early diagnosis of small
      hepato-cellular carcinoma. PATIENTS AND METHODS: One or several hepatic
      hypervascular nodules, with a diameter smaller than or equal to 3cm and suspected
      of corresponding to small hepato-cellular carcinoma, were detected during the
      arterial phase of spiral CT in 55 patients. The diagnosis of the main nodule
      could be established in 31 patients by pathologic examination, elevated alpha
      foeto-protein level or follow-up examination. RESULTS: Among the 31 studied
      nodules, 19 were hepato-cellular carcinomas (61%) and 12 were benign (39%). Seven
      (78%) of the 9 nodules>20mm and 12 (54%) of the 22 nodules<=20mmm were hepato
      cellular carcinomas. Three benign lesions (2 angiomas and 1 pseudo-nodule of
      hemodynamic origin) were showing typical radiological characteristics which
      retrospectively allowed their identification. On the other hand, the appearance
      of the 9 other benign nodules (29%) was exactly the same as the one of the hepato
      cellular carcinoma. CONCLUSION: Although, in cirrhotic patients, hepato-cellular
      carcinoma is the most frequent cause of detected nodules during the arterial
      phase of the spiral CT, 29% of hypervascular lesions<=3cm were benign in this
      study. In some cases, only follow-up examinations are able to confirm the
      diagnosis.

PMID- 12063427
TI  - [Mechanical small bowel obstruction due to bezoars: correlation between CT and
      surgical findings].
AB  - PURPOSE: To evaluate the correlation between computed tomography (CT) and
      surgery, for the diagnosis of bezoar in small bowel obstruction. To analyze the
      predisposing etiologic factors in this population. PATIENTS AND METHODS: We
      reviewed retrospectively between 1994 and 1999, 12 patients whose final diagnosis
      was small bowel obstruction with bezoar. All patients underwent helical CT scan
      before treatment. Eight patients were treated by surgery and 4 recovered with
      gastric aspiration. RESULTS: Small bowel obstruction was diagnosed by CT which
      always demonstrated a transition zone with ovoid intraluminal mass outlined by
      the bowel wall. The mass consisted of a mixture of soft tissue and internal gas
      bubbles like feces, suggesting bezoar. Surgery confirmed small bowel obstruction
      and presence of bezoar. Predisposing factors were: partial gastrectomy (2/12),
      post surgical adhesions (7/12), Meckel diverticulum (1/12) and dietary factors.
      CONCLUSION: We agree with the authors of the few prior CT reports and suggest
      that the characteristic CT appearance of mottled gas pattern is pathognomonic of
      bezoar with an excellent correlation in our population.

PMID- 12063428
TI  - [Antenatal diagnosis of a choledocal cyst].
AB  - Choledocal cyst is a rare anomaly that usually becomes symptomatic during
      childhood. Forty to sixty percent of choledocal cysts are diagnosed before 10
      years old, usually when complications occur. Today, because of advances in
      sonographic imaging, some cysts can de diagnosed before birth. The major
      prognostic factor is the development of complications such as hepatic fibrosis.
      Early treatment, after postnatal ultrasonography assessment, can reduce the
      incidence of serious complications. The authors report a case of a choledocal
      cyst diagnosed at 23 weeks gestation.

PMID- 12063429
TI  - [Urethral duplication type II in a male child: a case report].
AB  - Urethral duplication is a rare congenital anomaly, most common in male. The
      clinical presentation varies because of the various anatomical variant. A case of
      complete duplication with an accessory channel arising from a diverticulum, in a
      male child is reported. The clinical presentation, the imaging findings, and the
      management are described.

PMID- 12063430
TI  - [Aortic dissection and aberrant right subclavian artery: CT and MR findings].
AB  - A case of aortic dissection extending to an aberrant right subclavian artery seen
      at CT and MRI is reported. The clinical and imaging patterns of this rare disease
      are described and compared with those of the literature. Multiplanar views are,
      in this particular case, very useful for a precise assessment of the involved
      aberrant artery.

PMID- 12063431
TI  - [Distal glue embolization in a patient with gastrointestinal hemorrhage].
AB  - This is a case report, concerning the endovascular use of N-butyl-2
      cyanoacrylate, for treatment of a digestive hemorrhage from a distal branch of
      the superior mesenteric artery, leading to a successful outcome. This material,
      usually used in brain angiomas, constitutes an alternative for digestive
      embolization, which is quick, precise and definitive, without additional risk in
      experienced hands.

PMID- 12063432
TI  - [Quid. Alveolar microlithiasis].

PMID- 12063433
TI  - ["Evidence-based" Radiology].

PMID- 12063434
TI  - [Ruptured intracranial aneurysms: Occlusion by endovascular approach versus
      exclusion by microsurgery].

PMID- 12063435
TI  - The role of p53 mutation in BRCA1-associated ovarian cancer.
AB  - Ovarian cancer remains the most deadly gynecologic malignancy, resulting in an
      estimated 23,300 new cases and 13,900 deaths in the United States in the year
      2002. The discovery of the BRCA1 gene in 1994 has proven to be of great interest
      to the study of hereditary ovarian cancer. BRCA1 gene mutation confers a 16-42%
      lifetime risk of the development of ovarian cancer in those affected. Although
      BRCA1 functions as a tumor suppressor gene, conflicting studies have shown that
      BRCA1 dysfunction alone may not be sufficient for tumorigenesis. p53 is a tumor
      suppressor gene found to be dysfunctional in nearly 50% of all human cancers and
      in up to 80% of ovarian malignancies. The p53 protein product plays a crucial
      role in DNA surveillance and repair at the Gap 1-synthesis (G1-S) cell cycle
      checkpoint. Studies exhibiting the interaction of BRCA1 and p53 and the role of
      this interaction in DNA damage response led many investigators to suggest that
      p53 gene mutation is required for BRCA1-associated tumor development. This review
      explores the evidence for BRCA1 and p53 interplay, and outlines the crucial role
      p53 may play in BRCA1-related ovarian cancer.

PMID- 12063436
TI  - Down's syndrome screening in twin pregnancies by nuchal translucency measurement.
      Current concept.
AB  - During the last 2 decades various non-invasive Down syndrome (DS) screening
      methods were introduced in clinical practice. However, specific problems were
      encountered when these methods were applied for twin pregnancies. The current
      review aims to explore the problematic issue of antenatal DS screening in twins.
      The implication and the adjusted management in the attempt to achieve the best
      evaluation for this type of gestation is discussed. Overall more women with twin
      pregnancies (mainly those who conceived via assisted reproduction) are found
      false positive for DS. This is because the standard screening algorithms include
      maternal age. In addition, mid-trimester maternal serum screening is associated
      with a higher false positive rate; secondary to changes in the feto-placental
      endocrinologic metabolism in assisted conception pregnancies. Therefore, in twins
      mid-trimester maternal serum screening is of limited clinical value. In those
      pregnancies, DS screening by means of nuchal translucency measurements at 10-14
      weeks is associated with a lower false positive rate than mid-trimester serum
      screening. In addition, this screening method enables to specifically identify
      those fetuses at risk of DS and other anomalies, and thus contributes to a better
      outcome.

PMID- 12063437
TI  - Autoimmune factors in assisted reproduction.
AB  - The present review highlights recent studies that investigated the possible
      influences of autoimmune factors in reproductive success or failure. These
      factors include antiphospholipid antibodies, antithyroid antibodies, antinuclear
      antibodies, antisperm antibodies, and antiovarian antibodies. The majority of
      recent work has focused on these potential autoimmune factors; however,
      controversy still exists over indicated testing and treatment options. An
      association of antiphospholipid antibodies and recurrent pregnancy loss has been
      established, and treatment with subcutaneous heparin appears most efficacious.
      Other autoimmune factors are under investigation as markers of in vitro
      fertilization failure. Limited data from treatment trials are presented.

PMID- 12063438
TI  - HPV and pregnancy: diagnostic methods, transmission and evolution.
AB  - Pregnancy may foster the development of infections, in particular HPV infections.
      The aim of this study was to evaluate the entity of the relationship between HPV
      infection and pregnancy, with all the possible complications associated with this
      relationship. The pathology may be latent or manifest. Possible methods of
      diagnosis are clinical, namely gynecological examinations, PAP-tests, colposcopy
      or molecular, using viral DNA assay, Southern Blot, PCR, Hybrid Capture, etc. The
      prevalence of HPV infection in pregnancy varies between 5.4 and 68.8%. The
      population with the highest risk, also among pregnant women, are those under the
      age of 26. A number of different opinions emerge from the literature regarding
      the possibility of maternal-fetal virus transmission. None of the patients
      examined carried out treatment during pregnancy. The data reported in the
      literature on the relationship between HPV and pregnancy are highly discordant.
      This discrepancy depends on the diagnostic techniques used, the clinical history
      of the pregnant woman and the period of pregnancy when the sample is collected.
      Pregnancy enhances the development of the pathology which then often recedes in
      the postpartum. The possible maternal-fetal transmission of the virus is an
      important aspect: the letter is the main factor responsible for juvenile
      laryngeal papillomatosis. A number of Authors report an initial presence of HPV
      in newborns which often disappears within 6 months after birth.

PMID- 12063439
TI  - Motherhood, metabolic changes and evolution.
AB  - The most important metabolic changes in pregnancy are facilitated anabolism when
      food is available and accelerated catabolism during fasting. In combination with
      the acquisition of haemochorial placenta, bipedalism and obligatory prematurity
      at birth these evolutionary choices have been the prerequisite conditions for the
      rapid growth of the fetal brain and its further postnatal development.

PMID- 12063440
TI  - [Antiestrogen therapy in the treatment of breast neoplasms].
AB  - During recent years the development of hormone therapy for the treatment breast
      neoplasms has seen, in addition to classic aspecific antiestrogens (AE) like
      tamoxifen (TAM) and to a lesser extent toremifen, a major development of new
      molecules divided into two groups: the first is the so-called selective estrogen
      receptor modulators (SERMs), the most important of which is Raloxifen, which
      mediate estrogen-agonist effects in some tissues and estrogen-antagonist effects
      in others; the second group includes the aromatase inhibitors (AI), important
      enzymes for peripheral estrogen conversion. Some studies compare or associate
      classic AE with the new SERMs and AI, both in adjuvant therapy and in treatment
      for advanced forms. Other trials assess the anti-osteoporotic activity of some
      SERMs which present concomitant inhibitory activity on the breast and
      endometrium.

PMID- 12063442
TI  - [Cervical cytologic reports of ASCUS and LSIL. Cyto-histological correlation and
      implication for management].
AB  - BACKGROUND: The purpose of this retrospective study is to evaluate the
      appropriate management of ASCUS and LSIL pap smears by correlating the
      histological findings obtained by punch biopsy or excised specimens. METHODS: The
      study group included 584 women with abnormal pap smear: 358 with ASCUS and 226
      with LSIL cytological abnormalities. All patients underwent colposcopy and, if
      necessary, directed-punch biopsy. In case of biopsy-proven dysplasia a
      destructive or excisional treatment was performed, as indicated. RESULTS: The
      prevalence of HPV-CIN histological lesions in ASCUS patients was 36.3% and in
      LSIL patients was 67.7%. High grade CIN was observed in 15.7 and 20.8%
      respectively. In one ASCUS patients an invasive lesion was diagnosed on punch
      biopsy and two LSIL patients showed stromal invasion on the final histopathologic
      report on excised specimens. CONCLUSIONS: Patients with ASCUS or LSIL pap smear
      exhibit a wide spectrum of histological findings ranging from no pathologic
      abnormality to frequent high grade CIN and invasive carcinoma in rare cases.
      Because of the histological assessment by directed-punch biopsy and its
      therapeutical indications, colposcopic examination is recommended for all women
      with a cytologic diagnosis of ASCUS and LSIL.

PMID- 12063441
TI  - [Low-dose combination oral contraceptives use in women with uterine leiomyomas].
AB  - BACKGROUND: To evaluate the effects of the last generation of oral contraceptives
      (OC) on uterine leiomyomas. METHODS:  DESIGN: non-randomized perspective study on
      the effects of the last generation of oral contraceptives on uterine myomas
      during 24 months follow-up. SETTING: III Unit of Obstetrics and Gynecology,
      University of Bari. PARTICIPANTS: between 1999 and 2000 a total of 121
      asymptomatic women with only one subserous and/or intramural uterine myoma,
      having diameter pound 25 mm have been recruited. These patients were divided into
      two groups: the treatment group was composed of 53 women and was treated with
      last generation pill containing 20 microgram of ethynilestradiol and 150
      microgram of desogestrel or 20 microgram of ethynilestradiol and 75 microgram of
      gestodene, while the control group was composed of 68 women having no hormonal
      therapy. In both groups the uterine myoma size (evaluated by transvaginal
      ultrasonography), the duration of menstrual flow and the hematocrit at the time
      of recruitment, after 12 months and after 24 months were examined. RESULTS: Forty
      eight (90.6%) women belonging to the study group completed 2 years of OC use;
      only sixty women (88.2%) belonging to the control group completed the study. The
      use of the last generation oral contraceptives for 2 years didn't increase
      significantly uterine myomas size; besides after 24 months there was a
      significant reduction of more than two days of menstrual flow, and a significant
      increase of two and a half points of hematocrit. On the contrary, in the control
      group, we found a significant increase of uterine myoma volume, a not significant
      increase of menses duration and a not significant reduction of hematocrit.
      CONCLUSIONS: The prolonged use of the last generation of oral contraceptives does
      not affect the uterine myomas volume increase and furthermore it produces a
      significant reduction in the duration of menstrual flow with a significant
      increase in hematocrit.

PMID- 12063443
TI  - [The role of copper-releasing intrauterine device or levonorgestrel-releasing
      intrauterine system on uterine bleeding and iron status (prospective study of 8
      years)].
AB  - BACKGROUND: The aims of this study were the effects of copper intrauterine device
      (Cu-IUD) compared to progesterone (PRG-IUS) or levonorgestrel releasing
      intrauterine system (LNg-IUS) on menstrual bleeding, menorrhagia and
      dysfunctional uterine bleeding. The authors evaluated the effect of copper
      surface area on uterine bleeding. METHODS: Between March 1992 and November 1999,
      223 women, referred to I Institute of Obstetrics and Gynaecology University of
      Rome, were recruited in a prospective study with follow up at 3, 6 and 12 months
      to evaluate the incidence of endometrial pathology. The study includes 38 fertile
      women with regular menstruations and without intrauterine devices, as control
      group, and 185 patients with intrauterine devices, divides as follows: - 117
      copper-releasing intrauterine devices: 30 with a copper (Cu) surface area =200
      mm2, releasing 45 microgram Cu/24h (Nova T (R)); 27 with a copper surface area
      =250 mm2, releasing 50 microgram Cu/24h (Multiload 250 (R)); 25 with a copper
      surface area =375 mm2, releasing 65 microgram Cu/24h (Multiload 375 (R)); 20 with
      a copper surface area =384 mm2, releasing 100 microgram Cu/24h (No Gravid M (R));
      15 with a copper surface area =440 mm2, releasing 120 microgram Cu/24h (No Gravid
      0,5 (R)). - 68 progesterone/levonorgestrel-releasing intrauterine devices: 40
      progesterone-releasing intrauterine systems (Progestasert(R)); 28 levonorgestrel
      releasing intrauterine systems 20 mg/24h (Mirena (R)). A total of 211 subjects
      had data that were valid for analysis: 12 women out of 223 (5,4%) were excluded
      from the prospective study lost to follow-up. A venous blood sample for serum
      ferritin (mg/l), iron (mg/dl), hemoglobin (g/dl), hematocrit (%), blood cell
      count, MCHC and MCV was taken during follow-up. RESULTS: PRG or LNg-IUSs
      determined a significant reduction in menstrual blood loss and in irregular
      bleeding by gradually reducing endometrial fitness and vascularisation. Serum
      ferritin significantly increased in women inserted with LNg- IUSs already after 6
      months (26+/-22 e 28+/-14 microgram/l versus 32.5+/-19 e 34.5+/-25 microgram/l).
      Hemoglobin significantly increased (p>0.05) 6 months after insertion. On the
      contrary this did not occur with the insertion of Cu-IUDs. We observed that the
      increased amount of copper, released by IUD, causes increasing of bleeding.
      CONCLUSIONS: The LNg-IUS is a new contraceptive method combining the advantages
      of both hormonal and intrauterine contraception. In addition, it can be
      considered an alternative method in the treatment of menorrhagia and
      dysfunctional uterine bleeding. On the contrary, in women inserted with Cu-IUDs,
      the main reason of menorrhagia probably is due both to the shape of device and to
      copper surface area.

PMID- 12063444
TI  - Influence of sport and low animal saturated fats intake diet on lipid
      dismetabolisms in postmenopausal women.
AB  - BACKGROUND: An important aetiopathogenetic factor leading to menopausal age
      pathologies (such as hypertension, diabetes, cardiovascular diseases and so on)
      is certainly represented by the worsening of lipid dismetabolism. This condition
      is generally characterized by an increase in total mean cholesterol levels, LDL
      cholesterol (low density lipoprotein-cholesterol), VLDL-cholesterol (very low
      density lipoprotein-cholesterol), triglycerides, with reduction of HDL
      cholesterol (high density lipoprotein-cholesterol) mean levels. All these
      metabolic modifications are triggered or increased by the hypoestrogenemia
      typical of postmenopausal age. The aim of our study was to evaluate the influence
      on postmenopausal women's lipid metabolism of a low contribution of animal
      saturated fat diets, associated with physical training. METHODS: We enrolled in
      our study 36 mild hypercholesterolemic postmenopausal women (non smokers and not
      complaining of hypertension and diabetes) and we put them through aerobic
      training, consisting of 1 hour of a light continuous run, repeated 4 times per
      week. The final control of their metabolic status and of their lipid order was
      executed after 6 months, but during this period, all the women were observed bi
      weekly or monthly, to assure a high uniform compliance in the group. None of the
      women enrolled took specific drugs for the lipid metabolism during the study.
      RESULTS: After 6 months from the beginning of the diet, with associated physical
      training, an important weight loss was observed. Increases of HDL-cholesterol
      mean levels (p<0.05) associated with a decrease of total cholesterol mean levels
      (p<0.05) were reported in all the subject examined. A statistically non
      significant decrease in LDL and VLDL cholesterol mean levels was also noticed.
      CONCLUSIONS: A mild lipid dysmetabolism in postmenopause may be corrected
      advantageously by an opportune diet associated with moderate, but constant,
      physical training.

PMID- 12063445
TI  - Genital tuberculosis in a menopausal woman. A case report.
AB  - We have analysed the role played by genital tuberculosis (TBC) in Italy today,
      and in particular in L'Aquila, in the light of a worrying recrudescence. We
      report the case of a 64-year-old patient, in menopause for the past 11 years or
      so, referred to the Gynecology and Obstetrics Clinic of the University of
      L'Aquila, with an anamnesis of menometrorrhagia since the age of 55. The patient
      was studied from a gynecological and internist profile including the following
      procedures: gynecological examination and pap-test, colposcopy, transvaginal
      scan, chest X-ray, abdominal and pelvic CAT, laboratory tests and Mantoux
      reaction. The uterus was found to be fibromatous during the gynecological
      examination and scan, whereas colposcopy revealed a small ectropion and the
      presence of very adherent yellowish mucus. The Mantoux test was positive. CAT
      showed cicatricial sequelae in the pulmonary parenchyma. It was decided to
      perform curettage, but this was prevented by the presence of pyometra. The
      patient was treated with specific chemotherapy and then underwent total
      laparohysterectomy with bilateral adnexectomy. The histological findings
      confirmed genital TBC. Genital TBC is now undergoing a worrying recrudescence. We
      need to have a full knowledge of the pathology, the diagnostic means with which
      to discover it and the correct therapeutic instruments to overcome it.

PMID- 12063446
TI  - Where are we going with computer-assisted or robotic cardiac surgery? A piece of
      the totally endoscopic coronary bypass puzzle.

PMID- 12063447
TI  - The bioactive peptide endothelin causes multiple biologic responses relevant to
      myocardial and vascular performance after cardiac surgery.

PMID- 12063448
TI  - Extensive primary repair of the thoracic aorta in Stanford type A acute aortic
      dissection by means of a synthetic vascular graft with a self-expandable stent.
AB  - OBJECTIVES: To minimize any residual false lumen when operating on patients with
      an acute type A aortic dissection, we tried to perform extensive primary repair
      of the thoracic aorta with the modified elephant trunk technique. The early and
      midterm results of these surgical interventions are reported and evaluated.
      METHODS: Among the acute type A aortic dissections with extensive false lumen
      encountered since December 1997, 19 consecutive patients, 15 DeBakey type I with
      the tear in the ascending, transverse, or both aortas, and 4 DeBakey type III-D
      with the tear located in the descending aorta, underwent insertion of a synthetic
      graft with a distally anchored stent in the descending thoracic aorta. The
      interpolation method was used as an introducer combined with total replacement of
      the aortic arch by using a synthetic branching graft with only a median
      sternotomy. RESULTS: One patient died, and 18 were discharged after full
      recovery. Postoperative computed tomographic scans showed that no residual false
      lumina were present proximal to the diaphragmatic level, and no false lumina were
      found in 10 patients. Two patients with acute ischemia of the right kidney caused
      by narrowing of the true lumen, as demonstrated by radiographic computed
      tomography, improved significantly after surgical intervention with restoration
      of blood flow in the true lumen. Paraplegia was not observed in any patient.
      CONCLUSIONS: In emergency operations for an acute type A aortic dissection, the
      operation is often limited to replacing the ascending aorta because priority is
      given to saving the patient's life. However, it is possible to perform extensive
      primary repair of the thoracic aorta with relative safety by interpolating a
      synthetic graft with a self-expandable stent.

PMID- 12063449
TI  - Ischemic mitral regurgitation: intraventricular papillary muscle imbrication
      without mitral ring during left ventricular restoration.
AB  - OBJECTIVES: Functional mitral regurgitation in ischemic cardiomyopathy carries a
      poor prognosis, and its surgical management remains problematic and
      controversial. The aim of this study was to report the results of our surgical
      approach to patients who have had myocardial infarctions and have ventricular
      dilatation, mitral regurgitation, reduced pump function, pulmonary hypertension
      and coronary artery disease. This surgical approach consists of endoventricular
      mitral repair without prosthetic ring, ventricular reconstruction with or without
      patch, and coronary artery bypass grafting. PATIENTS: Forty-six patients (aged 64
      +/- 10 years) with previous anterior transmural myocardial infarction and mitral
      regurgitation comprised the study group. Indication for surgery was heart failure
      in 93% of cases; 25 patients were in New York Heart Association functional class
      IV and 17 were in class III. Mitral regurgitation was moderate to severe in 32
      cases (69%). RESULTS: All patients underwent coronary artery bypass grafting,
      with a mean of 3.2 +/- 1.3 grafts. Associated aortic valve replacement was
      performed in 4 cases. Global operative mortality rate was 15.2%. End-diastolic
      and end-systolic volumes significantly decreased after surgery (from 140 +/- 40
      to 98 +/- 36 mL/m(2) and from 98 +/- 32 to 63 +/- 22 mL/m(2), respectively, P
      =.001). Systolic pulmonary pressure decreased significantly (from 55 +/- 13 to 43
      +/- 16 mm Hg, P =.001). Ejection fraction did not change significantly.
      Postoperative mitral regurgitation was absent or minimal in 84% of cases; 1
      patient had severe mitral regurgitation necessitating valve replacement. New York
      Heart Association functional class significantly improved. The mean preoperative
      functional class was 3.4 +/- 0.6 (median 3, range 2-4); after the operation, this
      decreased to 1.9 +/- 0.7 (median 2, range 1-3, P <.001). Cumulative survival at a
      30-month follow-up was 63%. CONCLUSIONS: Our aggressive, combined surgical
      approach is aimed at correcting the three components of ischemic cardiomyopathy:
      relieving ischemia, reducing left ventricular wall tension by decreasing left
      ventricular volumes, and reducing volume overload and pulmonary hypertension by
      repairing the mitral valve. Despite a relatively high perioperative mortality
      rate, surviving patients benefitted from the operation, with improved clinical
      functional class and thus quality of life.

PMID- 12063450
TI  - Midterm follow-up of penetrating ulcer and intramural hematoma of the aorta.
AB  - OBJECTIVE: Most studies on variant forms of aortic dissection--penetrating ulcer
      and intramural hematoma--have focused on the initial presenting episode, with
      scant follow-up. This investigation provides midterm follow-up of penetrating
      ulcer and intramural hematoma to determine whether the aorta shows healing
      according to radiography, goes on to dilate, or tends to rupture during later
      follow-up. METHODS: Forty-five patients with penetrating ulcers (n = 26) or
      intramural hematomas (n = 19) were treated at our institution. Ten patients with
      penetrating ulcers were male and 16 were female, and their ages ranged from 54 to
      87 years (mean 72 years). Eight patients with intramural hematomas were male and
      11 were female, and their ages ranged from 54 to 88 years (mean 74 years). These
      patients all had symptoms of aortic disease. Patients with incidental imaging
      findings were not considered. RESULTS: In the group with penetrating ulcers,
      rupture occurred during the initial admission in 10 (38%) cases, 17 patients
      (65%) underwent surgery, and 22 patients (85%) survived to hospital discharge.
      Among those with intramural hematomas, rupture occurred during the initial
      admission in 5 cases (26%), 7 patients (37%) underwent surgery, and 16 patients
      (84%) survived to hospital discharge. Follow-up ranged from 1 month to 12.5 years
      (mean 3.4 years). No ischemic vascular complications occurred. Imaging follow-up
      was available for 26 of the 45 patients. Of these, 19% of lesions showed
      resolution, 23% had worsened, 39% had progressed to typical dissection, and 19%
      were unchanged. Six late deaths were known to be caused by rupture. In the group
      with penetrating ulcers, aortic diameter increased from 4.8 to 5.1 cm during the
      course of 14 months. In the group with intramural hematomas, aortic diameter
      increased from 5.3 to 5.9 cm during the course of 21 months. Overall survivals
      were 80% at 1 year, 73% at 3 years, and 66% at 5 years. CONCLUSIONS: Intramural
      hematoma and penetrating ulcer are lesions associated with advanced age. Women
      predominate. Penetrating ulcer and intramural hematoma rupture both early and
      late. Radiographically documented worsening, improvement, or frank dissection may
      occur with time. Aortic growth does occur (0.2 cm per year for penetrating ulcer
      and 0.4 cm per year for intramural hematoma). Vascular ischemic complications do
      not occur. Because of the high early rupture rate, the frequency of radiographic
      worsening, and the documented occurrence of late rupture, we now recommend
      surgical replacement of the aorta for these virulent vascular lesions as long as
      the patient's comorbidities do not preclude surgical intervention.

PMID- 12063451
TI  - Diameters of the thoracic aorta throughout life as measured with helical computed
      tomography.
AB  - OBJECTIVE: The use of helical computed tomography is well established in the
      evaluation of the thoracic aorta. Nevertheless, normal diameters and their
      changes during adult life according to this method are not available. We planned
      to set up normal diameters for the thoracic aorta of adults obtained by helical
      computed tomography. METHODS: Seventy adults, 17 to 89 years old, without any
      signs of cardiovascular disease were investigated with helical computed
      tomography. Aortic diameters were measured at seven predefined thoracic levels.
      RESULTS: Aortic diameters (mean +/- SD) were 2.98 +/- 0.46 cm at the aortic valve
      sinus, 3.09 +/- 0.41 cm at the ascending aorta, 2.94 +/- 0.42 cm proximal to the
      innominate artery, 2.77 +/- 0.37 cm at the proximal transverse arch, 2.61 +/-
      0.41 cm at the distal transverse arch, 2.47 +/- 0.40 cm at the isthmus, and 2.43
      +/- 0.35 cm at the diaphragm. Men had slightly longer diameters than did women.
      All diameters increased with age. There was no influence of weight, height, or
      body surface area. After normalization to the diameter at diaphragmatic level, no
      statistically significantly influential factor could be detected. CONCLUSIONS:
      This study delineates normal intrathoracic aortic diameters for helical computed
      tomography, including relationships with sex and age. Pathologic dimensions of
      the aorta should preferably be provided as percentiles or z scores.

PMID- 12063452
TI  - Circulatory benefits of diastolic counterpulsation in an ischemic heart failure
      model after aortomyoplasty.
AB  - OBJECTIVE: Aortomyoplasty is an experimental surgical procedure in which the
      latissimus dorsi muscle is wrapped around the thoracic aorta and stimulated to
      contract during diastole, providing diastolic counterpulsation. We hypothesized
      that aortomyoplasty could improve cardiac function in a chronic ischemic heart
      failure model, similar to the improvement seen with the intra-aortic balloon
      pump. METHODS: Six dogs (25-30 kg) successfully underwent aortomyoplasty followed
      by serial coronary microembolization. Ejection fraction decreased from 63.5% to
      36.5%. Two weeks after the final microembolization, the muscle was conditioned
      for 4 months to achieve fatigue resistance. One year after aortomyoplasty,
      hemodynamic studies during 1 hour of aortomyoplasty and 1 hour of intra-aortic
      balloon counterpulsation determined mean diastolic aortic pressure, peak left
      ventricular pressure, and endocardial viability ratio for assisted and unassisted
      beats. Cardiac output, stroke volume, and parameters of cardiac function were
      also measured. RESULTS: Endocardial viability ratio increased by 23.8% +/- 7.9%
      (P =.001) with aortomyoplasty counterpulsation and by 22.7% +/- 12.9% (P =.021)
      with the intra-aortic balloon pump. Both aortomyoplasty and the intra-aortic
      balloon pump significantly increased mean diastolic aortic pressure and reduced
      peak left ventricular pressure. Improvements in cardiac function with
      aortomyoplasty and the intra-aortic balloon pump were similar. Cardiac output
      increased from 2.61 +/- 0.88 to 3.07 +/- 1.06 L/min (P =.006), and index of
      afterload decreased from 5.4 +/- 1.4 to 4.8 +/- 1.4 mm Hg/mL (P =.02) during 1
      hour of aortomyoplasty counterpulsation. CONCLUSION: One year after the
      procedure, aortomyoplasty counterpulsation provided diastolic augmentation and
      improved cardiac performance similar to the improvement provided by the intra
      aortic balloon pump in a chronic ischemic heart failure model. Aortomyoplasty has
      the potential to benefit patients with ischemic heart disease refractory to
      current therapies.

PMID- 12063453
TI  - Novel cardioprotective effects of tetrahydrobiopterin after anoxia and
      reoxygenation: Identifying cellular targets for pharmacologic manipulation.
AB  - OBJECTIVES: Contemporary cardioprotective strategies to prevent perioperative
      ischemia-reperfusion injury have focused on the l-arginine nitric oxide pathway.
      Tetrahydrobiopterin is an absolute cofactor required for the enzyme nitric oxide
      synthase and is thus a critical determinant of nitric oxide production. We
      hypothesized that ischemia-reperfusion results in diminished levels of
      tetrahydrobiopterin, which might represent a key cellular defect underlying
      endothelial and myocyte dysfunction after ischemia-reperfusion. To this aim, we
      examined the effects of tetrahydrobiopterin supplementation in (1) an in vivo
      experimental model of global ischemia-reperfusion and (2) an in vitro human
      ventricular heart cell model of simulated ischemia-reperfusion. Measures of
      endothelial function, oxidant production, cell survival, and cardiac function
      were used to assess outcome. METHODS: In study 1 Wistar rats were divided into
      one of 2 groups (n = 10 per group). One group received tetrahydrobiopterin (25 mg
      x kg(-1) x d(-1) for 7 days), and the other group served as the control group.
      Hearts were subjected to 30 minutes of ischemia followed by 30 minutes of
      reperfusion, and left ventricular developed pressure, left ventricular systolic
      pressure, and left ventricular end-diastolic pressure were determined by using
      the modified Langendorff technique. In study 2 we quantitated myocardial
      malondialdehyde, a marker of lipid peroxidation, in ventricular tissues from both
      groups of animals using butanol phase extraction and spectrophotometric analysis.
      In study 3 coronary vascular responses were determined in vascular segments of
      the left coronary artery in both groups of animals after ischemia-reperfusion.
      Endothelium-dependent and endothelium-independent vasodilatation to acetylcholine
      and sodium nitroprusside, respectively, were compared between groups. In study 4,
      using a human ventricular heart cell model of simulated ischemia-reperfusion, we
      studied the effects of tetrahydrobiopterin (20 micromol/L) on cellular injury (as
      assessed by means of trypan blue uptake). RESULTS: After ischemia-reperfusion,
      myocardial dysfunction was evidenced by a decrease in left ventricular developed
      pressure and an increase in left ventricular end-diastolic pressure (P =.01
      compared with baseline). Hearts from tetrahydrobiopterin-treated rats exhibited
      protection against ischemia-reperfusion injury (left ventricular developed
      pressure: 74 +/- 4 vs control 42 +/- 8 mm Hg, P =.01; left ventricular end
      diastolic pressure: 12 +/- 3 vs 34 +/- 7 mm Hg, P =.01). Furthermore,
      tetrahydrobiopterin treatment attenuated the rise in malondialdehyde levels after
      ischemia-reperfusion (P =.01). After reperfusion, coronary endothelial function
      to acetylcholine was attenuated (P =.003 vs sham-treated mice), whereas responses
      to sodium nitroprusside remained unchanged. Tetrahydrobiopterin-treated rats
      exhibited an improvement in acetylcholine-mediated vasorelaxation (P =.01 vs
      ischemia-reperfusion group). Cellular injury, as assessed by means of trypan blue
      uptake, was higher in human ventricular heart cells subjected to simulated
      ischemia-reperfusion; this effect was prevented with tetrahydrobiopterin
      treatment (P =.001). CONCLUSIONS: Supplemental tetrahydrobiopterin provides a
      novel cardioprotective effect on left ventricular function, endothelial-vascular
      reactivity, oxidative damage, and cardiomyocyte injury after ischemia-reperfusion
      injury and might represent an important cellular target for future operative
      myocardial protection strategies.

PMID- 12063454
TI  - Hemostatic effects of tranexamic acid in elective thoracic aortic surgery: a
      prospective, randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: We studied the hemostatic effects of tranexamic acid in patients
      undergoing elective surgery involving the thoracic aorta. METHODS: In a double
      blind, randomized fashion, 60 consecutive patients were assigned to two treatment
      groups: 30 patients (placebo group) received infusion of saline solution, and 30
      (treatment group) received tranexamic acid (1 g before skin incision, an infusion
      of 400 mg/h during the operation, and 500 mg in the pump priming). Perioperative
      bleeding was considered as a primary outcome. Perioperative allogeneic
      transfusions, major thrombotic complications (myocardial infarction, pulmonary
      embolism, renal insufficiency), and surgical outcomes were also considered.
      RESULTS: Patients treated with tranexamic acid showed significant reductions in
      postoperative bleeding, both in terms of the amount collected during the first 4
      postoperative hours (median 307 mL, interquartile range 253-361 mL in the placebo
      group vs median 211 mL, interquartile range 108-252 mL in the treatment group, P
      =.002) and in terms of total bleeding (median 722 mL, interquartile range 574-952
      mL in the placebo group vs median 411 mL, interquartile range 313-804 mL in the
      treatment group, P =.04). Consequently, the number of patients transfused
      differed significantly between groups (21 patients [72.4%] in the placebo group
      vs 13 [44.8%] in the treatment group, P =.033). Patients in the treatment group
      showed significant reductions in the total amount for the entire group of packed
      red cells transfused (13,500 mL in the treatment group vs 28,000 mL in the
      placebo group, P =.012) and in the total amount of allogeneic transfusions
      (23,400 mL in the treatment group vs 53,000 mL in the placebo group, P =.024). No
      differences in perioperative thrombotic complications were found. CONCLUSIONS: In
      this initial series of patients undergoing thoracic aortic surgery, tranexamic
      acid appeared effective in reducing perioperative bleeding, with a significant
      reduction in the need for allogeneic transfusions and without any increased risk
      of thrombotic complications.

PMID- 12063455
TI  - Normothermia does not improve postoperative hemostasis nor does it reduce
      inflammatory activation in patients undergoing primary isolated coronary artery
      bypass.
AB  - BACKGROUND: Despite its common acceptance in clinical practice, the effective
      benefits of normothermic systemic perfusion during coronary artery bypass
      operations are far from established. METHODS: A total of 113 patients undergoing
      primary isolated coronary artery bypass were randomly assigned to normothermic
      (37 degrees C) or hypothermic (26 degrees C) systemic perfusion. The clinical
      course of the patients was prospectively recorded, and several inflammatory and
      fibrinolytic markers (C-reactive protein, fibrinogen, interleukin 6, plasminogen
      activator inhibitor 1, prothrombin time, activated partial thromboplastin time,
      platelets, and white blood cell counts) were determined before surgical
      intervention; 24, 48, and 72 hours thereafter; and at hospital discharge.
      RESULTS: Postoperatively, 2 in-hospital deaths occurred in the normothermic
      series and none in the hypothermic series. Four patients had a myocardial
      infarction, 1 had respiratory insufficiency, 1 had to be reoperated on for graft
      malfunction, and none had renal insufficiency in the hypothermic group versus 1
      patient with each of these complications in the normothermic series. Mean blood
      loss in the first 24 hours was 766 +/- 223 mL in the normothermic group and 740
      +/- 220 mL in the hypothermic group. None of these differences was statistically
      significant. Similarly, no significant difference in the postoperative level of
      any of the measured variables at any time point was evident between the patients
      in the normothermic and hypothermic groups. CONCLUSION: Normothermic systemic
      perfusion does not influence the clinical course or the extent of inflammatory
      and hemostatic activation in patients undergoing primary isolated coronary artery
      bypass.

PMID- 12063456
TI  - Gene therapy with adenovirus-mediated myocardial transfer of vascular endothelial
      growth factor 121 improves cardiac performance in a pacing model of congestive
      heart failure.
AB  - BACKGROUND: Myocardial ischemia is the most common cause of congestive heart
      failure. Angiogenic therapy has recently been demonstrated to enhance myocardial
      perfusion in the ischemic setting. We therefore hypothesized that administration
      of adenovirus encoding for vascular endothelial growth factor could be used to
      enhance myocardial function in a pacing-induced model of heart failure. METHODS:
      Yorkshire swine underwent a left thoracotomy with placement of a ventricular
      epicardial pacing system. Animals received adenovirus coding either for the 121
      amino-acid isoform of vascular endothelial growth factor (Ad(CU)VEGF121.1 group,
      n = 8) or a null vector coding for no genes (AdNull group, n = 8). The adenovirus
      was administered in the left ventricular free wall as 10 transepicardial
      injections of 100 microL each (total dose of 10(11) particle units). After a 1
      week recovery period, animals were paced at a rate of 230 beats/min for 7 days to
      induce heart failure. Transthoracic echocardiographic and sonomicrometric
      measurements were performed before pacing (baseline), on termination of pacing
      (day 0), and then weekly for 3 weeks. RESULTS: The fractional area change was
      significantly decreased in AdNull animals at day 0 after pacing compared with the
      Ad(CU)VEGF121.1 animals (29% +/- 14% vs 46% +/- 8%, P =.02). The fractional area
      change recovered to baseline values within 7 days in the Ad(CU)VEGF121.1 animals
      (62% +/- 7%) but remained significantly impaired in the AdNull group compared
      with that in the Ad(CU)VEGF121.1 animals up to day 21 (P =.04). Similarly,
      fractional wall thickening demonstrated a decrease at day 0 after pacing that was
      greater (P <.05) in the AdNull group compared with that in the Ad(CU)VEGF121.1
      group in 5 of 6 segments. Fractional wall thickening returned to levels
      approximating prepacing values in all segments within 7 days in the
      Ad(CU)VEGF121.1 group but remained significantly impaired compared with prepacing
      fractional wall thickening (P <.05) in the AdNull group in 5 of 6 segments up to
      day 21 after pacing. Segmental shortening, as measured by sonomicrometry, also
      was significantly decreased at day 7 in the AdNull group compared with that in
      the Ad(CU)VEGF121.1 group (10% +/- 4% vs 16% +/- 3%, P =.004) and remained
      significantly impaired (P <.05) in the AdNull group at day 14 and 21 when
      compared with baseline values. CONCLUSION: Preservation of cardiac performance
      and a more rapid recovery of myocardial function can be achieved in a model of
      pacing-induced cardiomyopathy with adenovirus-mediated administration of vascular
      endothelial growth factor compared with that seen in a null virus control group.
      These data suggest that angiogenic therapy may be useful clinically in treating
      cardiomyopathy.

PMID- 12063457
TI  - Increased endothelin-1 production in diabetic patients after cardioplegic arrest
      and reperfusion impairs coronary vascular reactivity: reversal by means of
      endothelin antagonism.
AB  - OBJECTIVES: Evidence has accrued to suggest that diabetic patients face an
      increased risk of ischemic events and low output syndrome and might mount an
      inordinate response to ischemia and reperfusion. Because hyperglycemia is a
      potent stimulus for endothelin-1 production, we hypothesized that increased
      production, action, or both of endothelin-1 in diabetes might represent an
      important mediator of endothelial dysfunction in patients with that disease. To
      this aim, we compared the effects of cardioplegic arrest and reperfusion on
      coronary sinus effluent endothelin-1 levels and atrial arteriolar vascular
      responses in diabetic and case-matched nondiabetic patients undergoing coronary
      artery bypass grafting. METHODS: In study 1 coronary sinus effluent endothelin-1
      levels were assessed at baseline and at 1 and 10 minutes after reperfusion in 13
      diabetic and 12 nondiabetic patients matched for age, ejection fraction,
      Parsonnet score, and crossclamp time. In study 2 vascular responses of atrial
      arterioles subjected to perioperative ischemia-reperfusion were evaluated with
      videomicroscopy. Atrial microvessels (from appendages) were obtained before and
      after removal of the aortic crossclamp, and vascular responses to exogenously
      administered endothelin-1 (10(-10) mol/L) and substance P (10(-8) mol/L) were
      studied in the presence or absence of BQ-123, an endothelin A receptor
      antagonist. RESULTS: Diabetic patients elaborated more endothelin-1 at 1 and 10
      minutes after reperfusion (P =.01). Endothelin-1-mediated vasoconstriction was
      similar in diabetic and nondiabetic atrial microvessels before cardioplegic
      arrest and cardiopulmonary bypass. After cardiopulmonary bypass and reperfusion,
      endothelin-1-mediated vasoconstriction was enhanced in both groups; however, this
      response was greater in microvessels from diabetic patients (P =.02). BQ-123, the
      endothelin A antagonist, attenuated the effects of bypass and reperfusion on
      endothelin-1-mediated vasoconstriction in both groups (P =.01). Substance P
      mediated vasodilatation was similar in diabetic and nondiabetic atrial
      microvessels before bypass. After bypass and reperfusion, substance P-mediated
      vasodilatation was diminished in both groups; however, this response was more
      pronounced in the diabetic group (P =.003). BQ-123 coincubation restored
      substance P-mediated vasodilatation in both groups. CONCLUSIONS: We determined
      the following: (1) the coronary effluent release of endothelin-1 is higher in
      diabetic than in nondiabetic patients after cardiopulmonary bypass and
      reperfusion; (2) diabetic coronary microvessels respond to bypass and reperfusion
      with greater endothelin-1-mediated vasoconstriction and diminished nitric oxide
      mediated vasodilatation; and (3) these effects are attenuated by endothelin
      antagonism. Endothelin-1 might be an important mediator of ischemia-reperfusion
      injury in patients with diabetes. Furthermore, use of endothelin receptor
      antagonists might be a novel strategy for improving the resistance of the
      diabetic heart to cardioplegic arrest and reperfusion.

PMID- 12063458
TI  - Hyperglycemia exaggerates ischemia-reperfusion-induced cardiomyocyte injury:
      reversal with endothelin antagonism.
AB  - OBJECTIVES: We have previously demonstrated an importance of endothelin-1 in
      diabetic patients undergoing bypass surgery. Recent evidence suggests that
      cardiomyocytes might also produce endothelin-1, which might directly impair
      myocyte contractility by increasing intracellular calcium levels. Because
      hyperglycemia is a potent stimulus of endothelin-1 production, we hypothesized
      that increased production, action, or both of endothelin-1 might be a mediator of
      direct cardiomyocyte injury in diabetes. Therefore we studied the effects of
      endothelin receptor blockers (BQ-123 and bosentan) on hyperglycemia-induced
      endothelin-1 production and cellular injury after ischemia-reperfusion. METHODS:
      Using a human ventricular heart cell model of simulated ischemia-reperfusion, we
      studied the effects of normoglycemia (5 mmol/L, 48 hours) and hyperglycemia (25
      mmol/L, 48 hours) on cellular injury and endothelin-1 production. Furthermore,
      the effects of selective endothelin-A and mixed endothelin-A/B receptor
      antagonism (with BQ-123 and bosentan, respectively) were evaluated. RESULTS:
      Cellular injury, as assessed by means of trypan blue uptake, was higher in human
      ventricular heart cells subjected to hyperglycemia and simulated ischemia
      reperfusion injury (P =.01); this effect was prevented with both BQ-123 and
      bosentan (P =.01). In addition, heart cells from the hyperglycemic group
      elaborated more endothelin-1 after ischemia-reperfusion (P =.02). CONCLUSIONS:
      Endothelin-1 production and cellular injury were greater in human ventricular
      heart cells subjected to hyperglycemic conditions and simulated ischemia
      reperfusion. These effects are mediated by endothelin-A receptors because both BQ
      123 and bosentan exerted similar degrees of protection. Endothelin receptor
      blockade is a novel strategy to improve the resistance of the diabetic heart to
      cardioplegic arrest and reperfusion.

PMID- 12063459
TI  - Totally endoscopic coronary artery bypass grafting on cardiopulmonary bypass with
      robotically enhanced telemanipulation: report of forty-five cases.
AB  - BACKGROUND: Robotically enhanced telemanipulation is a new powerful tool for
      minimally invasive procedures that allows totally endoscopic cardiac surgery.
      Between June 1999 and February 2001, 45 robotically enhanced totally endoscopic
      coronary artery bypass grafting procedures on the arrested heart were performed
      at our institution with the use of the da Vinci telemanipulation system
      (Intuitive Surgical, Inc, Mountain View, Calif). METHODS: In 37 patients a single
      vessel totally endoscopic coronary bypass operation was performed. Eight patients
      had different types of multivessel revascularization with both internal thoracic
      arteries. The initial conversion rate was 22% and dropped to 5% in the last 20
      patients. Two patients required reexploration via median sternotomy. The first 22
      patients had excellent graft patency on discharge. The procedural time for single
      vessel totally endoscopic bypass was 4.2 +/- 0.4 hours, bypass time was 136 +/-
      11 minutes, and aortic crossclamp time amounted to 61 +/- 5 minutes. CONCLUSION:
      The present data show the feasibility of closed chest single- and double-vessel
      revascularization, with good clinical results. However, procedural time is
      prolonged and the complex endoscopic and endoaortic occlusion techniques, as well
      as the extensive anesthesiologic monitoring, are demanding. The need for
      conversion to an open procedure diminished after a relatively short learning
      curve. All postulated benefits of totally endoscopic surgery other than excellent
      cosmesis must be evaluated in larger cohorts.

PMID- 12063461
TI  - Beating-heart mitral valve surgery: preliminary model and methodology.
AB  - OBJECTIVE: It is our hypothesis that image-guided mitral valve repair can be
      performed on the beating heart without cardiopulmonary bypass. As a first phase,
      we tested the feasibility of suturing the anterior and posterior mitral valve
      leaflets under image guidance. METHODS: In a water bath model, imaging approaches
      and suturing techniques were developed. Then, in 6 pigs, the left atrium was
      cannulated with a custom-made 15-mm valved port through a left thoracotomy.
      Atrial pressure was elevated by shunting of arterial blood to minimize air
      induction. A multiplane transesophageal echocardiographic probe was evaluated in
      the intraesophageal and epicardial positions. With a commercial endoscopic
      suturing device, sutures were placed through the anterior and posterior mitral
      leaflets under echocardiographic guidance. The animals were killed, and suture
      accuracy was evaluated by measuring the distance from the intended target areas
      on the anterior and posterior mitral leaflets. Air induction was monitored by
      echocardiography and graded as minimal to severe. RESULTS: There were no cases of
      hemodynamic instability or significant arrhythmia. The most effective imaging
      plane was a short-axis view that used the transesophageal echocardiographic probe
      epicardially at the heart base. Air induction was minimal in 2 animals, mild in
      3, and moderate in 1. Sutures were successfully placed 9 of 12 times (mean error
      0.8 +/- 0.5 cm). CONCLUSIONS: With these methods, off-pump, image-guided suturing
      of the beating-heart mitral valve was possible. This model may be a useful
      starting point for developing off-pump mitral valve repair procedures.

PMID- 12063460
TI  - Improved heart function with myogenesis and angiogenesis after autologous porcine
      bone marrow stromal cell transplantation.
AB  - OBJECTIVE: The study evaluated the utility of transplanting bone marrow stromal
      cells in a porcine myocardial infarction model. METHODS: A myocardial infarction
      was created by occluding the distal left anterior descending artery in pigs with
      coils and Gelfoam sponge. Sternal bone marrow was aspirated, and stromal cells
      were cultured and induced to differentiate to a myogenic phenotype with 5
      azacytidine. Four weeks after coronary artery occlusion, sestamibi technetium
      single-photon emission computed tomographic scans were performed, and then either
      a graft of 100 x 10(6) bone marrow stromal cells (n = 5, 30% labeled with
      bromodeoxyuridine) or culture medium (n = 6) was injected into the infarct
      region. Four weeks later the tomographic scans were repeated and cardiac function
      was assessed with pressure and volume measurements. Morphologic and histologic
      characteristics of the heart were also studied. RESULTS: Histologic examination
      found bromodeoxyuridine-labeled cells within the infarct region in islands that
      had sarcomeres and Z-bands and stained positively for cardiac specific troponin
      I. The bone marrow stromal cell transplant sites had a greater (P <.05) capillary
      density than did the control sites. The tomographic scans showed that the hearts
      with the cell transplants had increases in stroke volume, regional perfusion, and
      wall motion (P <.05 for all groups) relative to the control hearts. The pressure
      volume analysis showed improvement (P <.05) in end-systolic elastance and preload
      recruitable stroke work in the transplantation group relative to the control
      group. The left ventricular chamber size was smaller (P <.05) and the scar
      thickness was greater (P <.05) in the hearts with transplanted cells than in the
      control hearts (P =.06). CONCLUSION: 5-Azacytidine-treated bone marrow stromal
      cells transplanted into the myocardial infarct region formed islands of cardiac
      like tissue, induced angiogenesis, prevented thinning and dilatation of the
      infarct region, and improved regional and global contractile function.

PMID- 12063462
TI  - Surgical creation of aortopulmonary window in selected patients with pulmonary
      atresia with poorly developed aortopulmonary collaterals and hypoplastic
      pulmonary arteries.
AB  - OBJECTIVE: The morphologic characteristics of the pulmonary circulation vary
      widely in patients with pulmonary atresia, ventricular septal defect, and major
      aortopulmonary collaterals. Although we favor single-stage unifocalization and
      complete repair as the procedure of choice, a subgroup of patients who meet
      specific criteria have been treated with initial surgical creation of an
      aortopulmonary window. METHODS: Eighteen patients who were considered unsuitable
      candidates for single-stage repair underwent surgical creation of an
      aortopulmonary window. Selection criteria included the following: (1) presence of
      centrally confluent true pulmonary arteries 1.0 to 2.5 mm in diameter, with a
      well-developed peripheral arborization pattern; (2) multiple small aortopulmonary
      collateral vessels, most of which communicated with the true pulmonary arterial
      system; and (3) the presence of marked cyanosis. RESULTS: There were no early
      deaths, and the 2 late deaths were both unrelated to the procedure. Follow-up
      angiography (n = 17) demonstrated good growth of true pulmonary arteries in 15 of
      17 cases (88%). Mean pulmonary artery diameter increased from 1.76 mm to 3.45 mm.
      Subsequent operations have been performed in 15 of 18 cases (83%). Intracardiac
      repair with or without additional unifocalization was achieved in 8 of these 15
      (53%). Seven patients (47%) have undergone staged unifocalization as the next
      procedure; of these, 3 were able to have intracardiac repair. Thus 11 of the 15
      patients who have undergone second operations (73%) have had complete
      intracardiac repair. CONCLUSIONS: The initial surgical creation of an
      aortopulmonary window in carefully selected patients can increase the size of the
      true pulmonary arteries, making these patients better candidates for eventual
      intracardiac repair. The procedure should be avoided in patients with pulmonary
      overcirculation, a predominance of isolated supply collaterals, or true pulmonary
      arteries larger than 2.5 mm in diameter, and it is not applicable without a true
      pulmonary artery central confluence.

PMID- 12063463
TI  - How common is severe pulmonary hypertension after pediatric cardiac surgery?
AB  - BACKGROUND: Pulmonary hypertension may result in significant morbidity and
      mortality after pediatric cardiac surgery. The objective of this study was to
      determine the incidence and outcome of severe pulmonary hypertension, defined as
      a ratio of pulmonary to systemic arterial pressure equal to or greater than 1.0,
      after cardiac surgery in children. METHODS: Data from all children younger than
      18 years who had undergone cardiothoracic surgery from January 1, 1994, to
      December 31, 1998, were examined. To find children with severe pulmonary
      hypertension, we reviewed intensive care unit charts from patients who had been
      monitored with a pulmonary artery catheter after the operation (n = 151), had
      received mechanical ventilation for more than 4 days after the operation (n =
      124), or had died in the operating room or the intensive care unit (n = 22).
      Intraoperative and postoperative measurements of mean pulmonary arterial pressure
      and postoperative echocardiographic studies during the first 3 postoperative days
      were used to select the children. RESULTS: During the study period, 1349 children
      (including 164 neonates and 511 infants, median age 12 months) underwent cardiac
      operations with an overall perioperative mortality of 22 patients (1.6%). Twenty
      seven children (2%, median age 4.2 months) had severe pulmonary hypertension. Of
      these, 2 (7.4%) died within 30 days of the operation, and 3 others (11%) died
      within a year (median follow-up 53 months). Nitric oxide inhalation was used in 5
      of the 27 cases, and it probably saved the life of 1 patient, may have helped in
      1 case, and had no discernible effect in 3 cases. Severe pulmonary hypertension
      was most common after correction of complete atrioventricular septal defects
      (14%, n = 12/85). Thirteen of 131 children with Down syndrome (9.9%) had severe
      pulmonary hypertension. CONCLUSION: Severe postoperative pulmonary hypertension
      occurred after 2% of the cardiac procedures and in most cases was managed
      successfully with conventional treatment and had a favorable postoperative
      outcome. The low incidence relative to previous reports may reflect the benefits
      of early correction and improved intraoperative and postoperative care.

PMID- 12063464
TI  - Arterial switch operation with a single coronary artery.
AB  - OBJECTIVE: Our purpose was to evaluate the impact of coronary pattern on survival
      and reintervention in patients who underwent the arterial switch operation with a
      single coronary artery. METHODS: We conducted a retrospective analysis of 53
      patients with a single coronary artery who underwent the arterial switch
      operation between 1983 and 2000 at Children's Hospital Boston. Recent follow-up
      information was obtained for 40 of the 46 long-term survivors (mean follow-up 7.3
      +/- 4.5 years). RESULTS: Thirty-five patients had a single right coronary artery,
      with the left coronary artery posterior to the pulmonary artery in 27. Eighteen
      patients had a single left coronary artery (16 with the right coronary artery
      anterior to the aorta). Six of 7 total patients who died had a single right
      coronary artery; all died before 1992. There were 5 early deaths, all with a
      single right coronary artery, with 4 deaths due to coronary malperfusion.
      Survivals for all patients were 91% at 6 months and 87% at 1, 5, and 10 years
      after the arterial switch operation. Survival figures were lower for patients
      having a single right ostium with the left main coronary artery posterior to the
      pulmonary artery compared with all other subtypes (P =.02, log-rank test). Seven
      patients had reintervention, 4 because of right ventricular outflow tract
      obstruction, 1 for heart transplantation, 1 for mitral valve repair and 1 for
      pacemaker implantation. Freedom from reintervention for all patients was 96% at 6
      months, 92% at 1 year, 86% at 5 years, and 82% at 10 years after the arterial
      switch operation, with lower rates for patients having a single left ostium with
      the right coronary artery anterior to the aorta (P =.0003, log-rank test).
      CONCLUSIONS: In the current era, the arterial switch operation with a single
      coronary artery can be performed safely irrespective of the coronary anatomy.
      Risk of reintervention is higher in patients having a single left ostium with the
      right coronary artery anterior to the aorta.

PMID- 12063465
TI  - Disparities in surgical resection of early-stage non-small cell lung cancer.
AB  - OBJECTIVES: The aim of our study was to identify the factors that determined
      whether a patient underwent surgery and its impact on patient outcome. METHODS: A
      retrospective evaluation of the records of all patients diagnosed with resectable
      stages I and II non-small cell lung cancer between 1990 and 1998 at the
      University of Arkansas and Veterans Administration Hospitals were included in the
      study. Demographic, clinical, pathologic, and outcome data were captured.
      Analysis was conducted to identify prognostic factors as well as factors leading
      to surgical treatment disparities. RESULTS: A total of 551 patients were
      included; 490 (89%) were men, 480 (87%) were white, and 315 (57%) were aged >65
      years. Median follow-up of these patients was 24 months (1-109 months). Surgery
      was performed on 455 patients (82.6%); 26 patients received nonsurgical treatment
      including chemotherapy, radiation therapy, or both, and 70 patients did not
      receive any type of treatment. A univariate analysis revealed that age, race,
      sex, and forced expiratory volume in the first second were significantly
      different between the surgery and no surgery groups. However, a multivariate
      analysis showed that age, forced expiratory volume in 1 second, and hemoglobin
      were significantly different between both groups. The median overall survival was
      45.5 months (1-109 months) for the surgically treated patients compared with 12.0
      months (1-86 months) for those who did not undergo surgery (P <.0001).
      CONCLUSION: Elderly patients with early-stage non-small cell lung cancer are less
      likely to undergo a potentially curative surgical resection. Racial and sex
      disparities may be due to other comorbidities.

PMID- 12063466
TI  - Autologous tissue-engineered trachea with sheep nasal chondrocytes.
AB  - OBJECTIVE: This study was designed to evaluate the ability of autologous tissue
      engineered trachea shaped in a helix to form the structural component of a
      functional tracheal replacement. METHODS: Nasal septum were harvested from six 2
      month-old sheep. Chondrocytes and fibroblasts were isolated from tissue and
      cultured in media for 2 weeks. Both types of cells were seeded onto separate
      nonwoven meshes of polyglycolic acid. The chondrocyte-seeded mesh was wound
      around a 20-mm-diameter x 50-mm-long helical template and then covered with the
      fibroblast-seeded mesh. In 2 separate studies the implants were placed either in
      a subcutaneous pocket in the nude rat (rat tissue-engineered trachea) or in the
      neck of a sheep (sheep tissue-engineered trachea). Rat tissue-engineered tracheas
      were harvested after 8 weeks and analyzed by means of histology and biochemistry.
      Sheep tissue-engineered tracheas were harvested from the neck at 8 weeks and
      anastomosed into a 5-cm defect in the sheep trachea. RESULTS: Sheep receiving
      tissue-engineered trachea grafts survived for 2 to 7 days after implantation.
      Gross morphology and tissue morphology were similar to that of native tracheas.
      Hematoxylin-and-eosin staining of rat tissue-engineered tracheas and sheep tissue
      engineered tracheas revealed the presence of mature cartilage surrounded by
      connective tissue. Safranin-O staining showed that rat tissue-engineered tracheas
      and sheep tissue-engineered tracheas had similar morphologies to native tracheal
      cartilage. Collagen, proteoglycan, and cell contents were similar to those seen
      in native tracheal tissue in rat tissue-engineered tracheas. Collagen and cell
      contents of sheep tissue-engineered tracheas were elevated compared with that of
      normal tracheas, whereas proteoglycan content was less than that found in normal
      tracheas. CONCLUSIONS: This study demonstrated the feasibility of recreating the
      cartilage and fibrous portion of the trachea with autologous tissue harvested
      from single procedure. This approach might provide a benefit to individuals
      needing tracheal resection.

PMID- 12063467
TI  - Radical sternectomy and primary musculocutaneous flap reconstruction to control
      sternal osteitis.
AB  - OBJECTIVE: Sternal osteitis after median sternotomy is associated with
      considerable morbidity and mortality. The use of muscle and omentum flaps has
      been proved as valid adjunct to combat these severe infections. In this study we
      present our experience with a more radical approach. METHODS: Sternectomy
      consisted of the resection of the entire sternum, including the costochondral
      arches and the sternoclavicular joints, and was followed by the repair of the
      defect with musculocutaneous flaps without any restabilization of the thoracic
      wall. Thirteen patients received a vertical rectus abdominis musculocutaneous
      flap, 14 patients received a pedicled latissimus dorsi musculocutaneous flap, and
      12 patients received a free latissimus dorsi musculocutaneous flap (total of 40
      flaps in 39 patients of 66 patients who required surgical revision for sternal
      osteitis of 6078 total patients with sternotomies). RESULTS: Two patients died
      within 30 days after the operation (early mortality of 5.1%); however, they did
      not die of sternal infection, which was cured without any recurrence in all
      cases. Seventeen patients (44%) required secondary, mostly minor operations for
      local complications. Despite some paradoxic chest movements, the patient
      satisfaction rating was unanimously high at the long-term follow-up (0.4 to 8.5
      years, median 2.3 years). The short- and long-term complication rates were
      similar in the three groups. CONCLUSION: We conclude that radical sternectomy and
      immediate musculocutaneous flap repair provided definitive control of sternal
      infection in even the most severe cases, thus reducing infection-related
      mortality. The trade-off was a substantial rate of local complications; however,
      these did not cause any relevant morbidity.

PMID- 12063468
TI  - Antisense therapy for malignant mesothelioma with oligonucleotides targeting the
      bcl-xl gene product.
AB  - OBJECTIVE: Malignant pleural mesothelioma is resistant to conventional therapies
      and to apoptosis. The bcl-2 family genes are major determinants of apoptotic
      homeostasis. Malignant pleural mesothelioma lines and tumors rarely express the
      antiapoptotic Bcl-2 protein but routinely express the antiapoptotic protein Bcl
      xl and the proapoptotic proteins Bax and Bak. We have previously shown
      pharmacologic inhibition of bcl-xl expression in malignant pleural mesothelioma
      can lead to apoptosis, so we sought to determine whether antisense
      oligonucleotides directed at bcl-xl messenger RNA would engender apoptosis,
      possibly through a "forced imbalance" of bcl-2 family proteins. METHODS:
      Malignant pleural mesothelioma lines REN (epithelial) and I-45 (sarcomatous) were
      exposed to modified bcl-xl antissense oligonecleotides directed near the
      messenger RNA initiation sequence with and without a liposomal delivery system.
      Untreated cells and bcl-xl sense oligonucleotides were controls. Cell viability
      was measured by colorimetric assay, and apoptosis was evaluated with Hoechst
      staining and sub-G(1) fluorescence-activated cell sorter analysis. RESULTS: Bcl
      xl protein expression after antisense oligonucleotides was downwardly regulated
      in both cell lines relative to sense oligonucleotides (>65%). Significant
      cellular killing in both the I-45 and REN cell lines was achieved with antisense
      oligonucleotides (compared with sense oligonucleotides) without (P =.003 and.006,
      respectively) and with (P =.006 and.0005, respectively) liposomal delivery.
      Hoechst staining and sub-G(1) fluorescence-activated cell sorter analysis
      demonstrated apoptosis to be the mechanism of cellular death. Use of a liposomal
      delivery system increased therapeutic effect and allowed lower doses of antisense
      oligonucleotides. CONCLUSION: Antisense oligonucleotides directed at the bcl-xl
      gene product engender apoptosis in mesothelioma cell lines. The therapeutic
      potential of inhibiting expression of this protein in mesothelioma should be
      evaluated.

PMID- 12063469
TI  - Cardiopulmonary bypass reduction of bronchial blood flow: a potential mechanism
      for lung injury in a neonatal pig model.
AB  - BACKGROUND: During total cardiopulmonary bypass, blood flow to the lungs is
      limited to flow through the bronchial arteries. We tested the hypothesis that
      bronchial blood flow during cardiopulmonary bypass is insufficient to prevent
      ischemia of the lung and that perfusion of the pulmonary arteries with oxygenated
      blood during bypass would reduce lung injury. METHODS: Eighteen piglets (5.0 +/-
      0.5 kg) were subjected to 120 minutes of normothermic total cardiopulmonary
      bypass, followed by 60 minutes of postbypass perfusion. Nine of them received
      continuous pulmonary perfusion with oxygenated blood during bypass. Six
      additional piglets served as a control group and were mechanically ventilated
      after sternotomy for 180 minutes only. We quantitated bronchial arterial blood
      flow, tissue lactate content, and alveolar septal thickness and surface area. We
      also obtained bronchioalveolar lavage fluid samples. RESULTS: With the beginning
      of cardiopulmonary bypass, bronchial arterial blood flow decreased to 13% of
      baseline (42.1 +/- 10.4 to 5.6 +/- 1.0 mL/min). It remained decreased until the
      end of bypass and returned to starting levels 60 minutes after bypass. The
      decrease in bronchial blood flow was associated with a 3-fold increase in tissue
      lactate content. At the end of reperfusion there was a 2-fold increase in
      alveolar septal thickness and significant accumulations relative to control in
      the bronchoalveolar lavage fluid of albumin, lactate dehydrogenase, neutrophils,
      and elastase. Controlled pulmonary perfusion significantly ameliorated all the
      observed changes. CONCLUSION: Cardiopulmonary bypass caused a reduction in
      bronchial arterial blood flow, which was associated with injury of the lung.
      Controlled pulmonary perfusion reduced injury to the lung during bypass. The
      inflammatory response, as evidenced by bronchoalveolar lavage fluid, may be
      caused by ischemia.

PMID- 12063470
TI  - Intrapericardial left pneumonectomy after induction chemotherapy: the risk of
      cardiac herniation.

PMID- 12063471
TI  - Hodgkin disease of thymic origin.

PMID- 12063472
TI  - Living-donor single-lobe lung transplantation for primary pulmonary hypertension
      in a child.

PMID- 12063473
TI  - Long-term survival of patients with univentricular heart not treated surgically.

PMID- 12063475
TI  - Aortic arch reconstruction in neonates without hypothermic circulatory arrest.

PMID- 12063474
TI  - Supravalvular pulmonary stenosis as a late complication of surgery for anomalous
      coronary origin.

PMID- 12063476
TI  - Aortic valve malformations and pulmonary autograft root dilatation.

PMID- 12063477
TI  - Trichotillomania.
AB  - Trichotillomania is a neglected psychiatric disorder with dermatologic expression
      that has only recently received research attention. On the basis of clinical
      data, trichotillomania appears to be far more common than previously believed.
      Like obsessive-compulsive disorder, the hair-pulling behavior is recognized as
      senseless and undesirable but is performed in response to several emotions and
      affects, such as increasing anxiety, or unconscious conflicts with resultant
      tension relief. The condition may be episodic but is usually chronic and
      difficult to treat. On the basis of possible medical and psychiatric
      complications, it is important that the diagnosis is exact and early. We describe
      the comorbidity and the phenomenology of trichotillomania, paying attention to
      the possible available treatments. (J Am Acad Dermatol 2002;46:807-21.) LEARNING
      OBJECTIVE: At the conclusion of this learning activity, participants should be
      familiar with clinical and histologic aspects of trichotillomania and should be
      able to cope with the risks of medical and psychiatric complications in these
      patients. Finally, participants will be able to easily interact with
      psychiatrists, when needed, to identify the most successful treatment.

PMID- 12063478
TI  - Ofuji's disease: a report on 20 patients with clinical and histopathologic
      analysis.
AB  - BACKGROUND: Ofuji's disease, also referred to as classic eosinophilic pustular
      folliculitis, is a rare dermatosis of unknown origin for which there is no
      uniformly effective treatment. OBJECTIVES AND METHODS: Twenty patients with
      Ofuji's disease (classic eosinophilic pustular folliculitis) evaluated in our
      department from January 1978 to June 1999 were studied clinically and
      histopathologically. Laboratory data, treatments, and clinical courses were
      evaluated in 12 of these individuals. RESULTS: Nissl modified staining revealed
      moderate increases of mast cells around hair follicles and sebaceous glands in
      all 20 patients; the majority of the infiltrating mast cells were tryptase
      positive and chymase-negative. Eight of 11 patients treated with oral
      indomethacin responded completely. CONCLUSIONS: Indomethacin is an effective
      therapy for Ofuji's disease. Tryptase-positive and chymase-negative mast cells
      might play some role in the pathogenesis of Ofuji's disease.

PMID- 12063479
TI  - Rash severity in herpes zoster: correlates and relationship to postherpetic
      neuralgia.
AB  - Baseline and follow-up data from 4 samples of immunocompetent patients with
      herpes zoster who participated in clinical trials of the antiviral agent
      famciclovir were examined (N = 1778). In both univariate and multivariate
      analyses, severe rash (ie, >50 lesions, defined as papules, vesicles, or crusted
      vesicles) was significantly associated with older age, male sex, severe pain,
      primary involvement of nontrigeminal dermatomes, and a greater number of affected
      dermatomes. In addition, severe rash predicted the presence of pain 3 months
      later. The results indicate that severe rash is more common in patients with
      herpes zoster who are older and who have more severe acute pain and confirm that
      severe rash is a risk factor for prolonged pain.

PMID- 12063480
TI  - A multicenter, double-blind, randomized, placebo-controlled study of the efficacy
      and safety of botulinum toxin type A in the treatment of glabellar lines.
AB  - BACKGROUND: Botulinum toxin type A (BTX-A) is widely used for facial esthetics
      but is incompletely studied. OBJECTIVE: This study was conducted to evaluate the
      efficacy and safety of BTX-A treatment of glabellar lines. METHODS: Patients with
      moderate to severe glabellar lines at maximum frown received intramuscular
      injections of 20 U BTX-A (BOTOX, Allergan, Inc, Irvine, Calif) or placebo into 5
      glabellar sites. Patients were followed up for 120 days after injection. Outcome
      measures were physician rating of glabellar line severity at maximum frown and
      rest, patient assessment of improvement, and vital sign and adverse event
      monitoring. RESULTS: Two hundred sixty-four patients were enrolled (BTX-A: 203,
      placebo: 61). There was a significantly greater reduction in glabellar line
      severity with BTX-A than with placebo (all measures, every follow-up visit; P
      <.022). The effect was maintained for many patients through day 120. There was a
      low occurrence (5.4%) of mostly mild blepharoptosis in the BTX-A group.
      CONCLUSION: BTX-A injections are safe and effective in reducing the severity of
      glabellar lines.

PMID- 12063481
TI  - The direct cost of care for psoriasis and psoriatic arthritis in the United
      States.
AB  - BACKGROUND: Relatively little information is available in the literature
      concerning the cost of psoriasis in the United States, and much of that
      information is out of date. OBJECTIVE: The present analyses estimate the direct
      cost of medical care for psoriasis (including psoriatic arthritis) from a
      societal perspective among adults in the United States. METHOD AND DATA: The
      costs of hospitalizations, outpatient and physician office visits, prescription
      and over-the-counter (OTC) medications, and medical procedures were estimated
      from the literature, analysis of publicly available health databases (Health and
      Nutrition Examination Survey, National Hospital Discharge Survey, Medicare Public
      Use Files, National Ambulatory Medical Care Survey, and the National Hospital
      Ambulatory Medical Care Survey), and analysis of privately available health
      databases (United Health Care/Diversified Pharmaceutical Services, the Medstat
      Group diagnosis-related group guide, and the National Disease and Therapeutic
      Index). Costs were expressed as of 1997 by using Medicare and health maintenance
      organization reimbursement rates and wholesale drug costs. Costs of OTC
      medications were derived by adjusting a previous estimate in the literature for
      inflation in over-the-counter drugs and population increases. RESULTS: The cost
      of illness for the approximately 1.4 million individuals with clinically
      significant disease is substantial-approximately $30.5 million for
      hospitalizations, $86.6 million for outpatient physician visits, $27.4 million
      for photochemotherapy, $147.9 million for dermatologic prescription drugs, and
      $357.2 million for OTC drugs, for a total direct cost of $649.6 million.
      CONCLUSION: Cost estimates from this study are substantially less than those
      found in previous studies ($1.09 billion and $4.32 billion after adjustment of
      estimates in the literature for medical inflation and population increases). This
      appears to be principally a result of decreases in hospitalization rates since
      1979 and the valuation methodology per unit of medical services (with prior
      studies using "list" prices and the current study using reimbursement rates).

PMID- 12063483
TI  - Psoriasis of early and late onset: a clinical and epidemiologic study from Spain.
AB  - BACKGROUND: The existence of 2 distinct forms of psoriasis related to age at
      onset has been postulated. However, precise data regarding the clinical and
      epidemiologic characteristics of psoriasis depending on the age at onset are
      still lacking. OBJECTIVE: The purpose of this study was to define the clinical
      and epidemiologic features of this disease in Spain and to compare patients with
      psoriasis of early and late onset. METHODS: An observational, analytic, cross
      sectional, multicenter study was carried out. From January 1999 to November 1999,
      179 participating dermatologists completed a questionnaire detailing the clinical
      and epidemiologic features of the first 10 consecutive patients with psoriasis
      seen in their clinical practice. The sample distribution was proportional to the
      Spanish population. Both statistical and descriptive analyses were performed.
      RESULTS: Available data were obtained from 1774 patients. The onset of the
      disease before 30 years of age was significantly associated with a higher
      incidence of family history of psoriasis, a more severe and extensive cutaneous
      involvement, and greater psychosocial impact. Guttate psoriasis, nail
      involvement, evidence of precipitating factors, and a recurrent clinical course
      were more frequent in this group of patients. Patients with psoriasis of late
      onset had a less severe clinical course and a more continuous evolution.
      Palmoplantar pustulosis was more frequent in this group of patients. No
      significant relationship was detected between the age at onset and development of
      joint involvement. CONCLUSION: Patients with early and late onset psoriasis often
      show different clinical and evolutionary features. From the analysis of our data,
      it seems that 2 different groups of patients with psoriasis related to age at
      onset can be defined.

PMID- 12063482
TI  - Erythropoietic protoporphyria: altered phenotype after bone marrow
      transplantation for myelogenous leukemia in a patient heteroallelic for
      ferrochelatase gene mutations.
AB  - Acute myelogenous leukemia occurred in a 47-year-old woman whose 25-year history
      of cutaneous photosensitivity had been undiagnosed until abnormally high
      erythrocyte, plasma, and fecal protoporphyrin levels were discovered during
      evaluation for her hematologic disorder. She was found to be heteroallelic for
      ferrochelatase gene mutations, bearing a novel missense mutation caused by a C185
      ->G (Pro62-->Arg) transversion in exon 2 of one allele, and a previously
      described g-->a transition at the +5 position of the exon 1 donor site of the
      other allele, confirming a diagnosis of erythropoietic protoporphyria. Successful
      bone marrow transplantation from her brother, who is a mildly affected bearer of
      the second mutation, resulted in remission of the leukemia and in conversion of
      the protoporphyria phenotype of the recipient to one resembling that of the
      donor.

PMID- 12063484
TI  - Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients.
AB  - Analysis of data of 6931 patients with cutaneous melanoma seen at the Department
      of Dermatology and Allergology at the Ludwig-Maximilians-University of Munich
      between 1977 and 1998 identified 36 patients in whom cutaneous melanomas
      developed during childhood or adolescence (age <18 years). Clinical courses of
      all patients and histopathologic characteristics of the lesions were reviewed.
      Seventeen patients were boys and 19 patients were girls. The median ages of the
      boys and girls were 15 and 16 years, respectively (range, 2-17 years). Thirty-one
      patients presented with nonmetastatic primary melanomas and 5 patients presented
      with metastatic melanoma. Forty-seven percent of the primary lesions were
      associated with a nevus (22% with congenital nevi and 25% with acquired nevi).
      Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm (mean, 1.67
      mm). All patients with primary melanomas received surgical therapy; patients with
      metastatic disease received chemotherapy, radiation therapy, or both. Relative 5
      year survival was 87.5% for the group of patients younger than 18 years. Similar
      to experience in adult patients, survival strongly correlated with tumor
      thickness and clinical stage at the time of diagnosis. The data emphasize that a
      high index of suspicion for cutaneous melanoma is needed by clinicians assessing
      melanocytic lesions in children and adolescents for early diagnosis. Reduction of
      the melanoma mortality rate in children and adolescents will be achieved through
      identification of patients at increased risk.

PMID- 12063486
TI  - Treatment of psoriasis with the chimeric monoclonal antibody against tumor
      necrosis factor alpha, infliximab.
AB  - BACKGROUND: Psoriatic skin lesions in patients with Crohn's disease or psoriatic
      arthritis have shown improvement during infliximab treatment. OBJECTIVE: The
      purpose of our study was to systematically assess the effects of infliximab in
      patients with psoriatic skin lesions. METHODS: Eight patients with severe
      psoriasis were enrolled in an open-label clinical trial. Patients received
      infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and
      Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6,
      8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the
      follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic
      sections were prepared from biopsy specimens of uninvolved skin and of psoriatic
      lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a
      microscopic micrometer grid. RESULTS: The PASI diminished from 21.8 +/- 4.2 (mean
      +/- SE) at week 0 to 3.4 +/- 2.0 at week 10, corresponding to 10.7% +/- 4.3% of
      the original values (100%); on follow-up at week 14, the PASI was 7.1 +/- 2.7 (or
      still 33.3% +/- 11.3% of the values at week 0). Pruritus decreased from 2.5 +/-
      0.26 at week 0 to 0.43 +/- 0.2 at week 10 and to 0.83 +/- 11.3 at week 14.
      Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 +/- 0.06
      mm at week 0 to 0.14 +/- 0.02 mm at week 10. No adverse effects other than
      fatigue during infusion on some occasions were reported. CONCLUSION: Although
      psoriasis tends to recur beyond 2 months of the infusions, this open study
      provides evidence that infliximab is an effective treatment.

PMID- 12063485
TI  - Allergic contact dermatitis in response to budesonide reactivated by inhalation
      of the allergen.
AB  - BACKGROUND: Up to 5% of patients with dermatitis who are consecutively patch
      tested are allergic to one or more corticosteroids. However, few reports of
      allergic mucosal and skin symptoms in patients with asthma and rhinitis caused by
      inhaled corticosteroids exist. OBJECTIVE: Our purpose was to determine whether
      inhalation of budesonide would result in reactivation of patch test reactions
      caused by budesonide. METHODS: The study, which was randomized, double-blind, and
      placebo-controlled, was ethically reviewed by the Medical Faculty, University of
      Lund, Sweden. Fifteen nonasthmatic patients who were initially given a diagnosis
      of budesonide hypersensitivity on patch testing from less than 1 up to 8 years
      before the study were provoked with budesonide or placebo by inhalation 6 weeks
      after they had been patch tested with budesonide, its R and S diastereomers, and
      potentially cross-reacting substances. Lung function was studied by using
      spirometry and repeated peak expiratory flow measurements. RESULTS: In 4 of 7
      patients who inhaled budesonide, reactivation of previously positive patch test
      reactions was noted within 24 hours, in contrast to 0 of 8 patients who inhaled
      placebo (P =.026). No adverse pulmonary responses could be detected. CONCLUSION:
      This study shows that allergic skin reactions may occur in patients with contact
      allergy to budesonide when inhaled forms of the drug are used.

PMID- 12063487
TI  - Interstitial granulomatous dermatitis with plaques.
AB  - BACKGROUND: Interstitial granulomatous dermatitis is a histopathologic pattern
      with variable clinical appearance associated with autoimmune systemic diseases.
      The frequency of its different cutaneous expressions and its association with
      autoimmune diseases are not known. OBJECTIVE: We describe the clinical,
      serologic, and histologic features in 17 patients with interstitial granulomatous
      dermatitis with a clinical presentation consisting of large erythematous plaques.
      METHOD: Skin biopsy specimens fulfilling criteria for diagnosis of interstitial
      granulomatous dermatitis were selected and correlated with the clinical and
      laboratory findings. RESULTS: The study included 1 man and 16 women with
      multiple, asymptomatic, round to oval, erythematous plaques, most often on folds
      of the skin, in a bilateral and somewhat symmetric distribution. Most of patients
      had rheumatoid polyarthralgias along with various serologic abnormalities, often
      connected to collagen vascular diseases. Histologic examination disclosed a
      distinctive interstitial granulomatous dermatitis characterized by a diffuse
      infiltration of the interstitium by histiocytes with piecemeal fragmentation of
      collagen and formation of small granulomas around degenerative areas in concert
      with variable numbers of polymorphonuclear leukocytes sprinkled within the
      infiltrate. Churg-Strauss granulomas in miniature and flame figures were
      occasionally observed and indicated continued or increased activity of the
      associated autoimmune disease(s). CONCLUSIONS: Interstitial granulomatous
      dermatitis with plaques is a distinct entity with highly reproducible clinical
      and histopathologic features; recognition of these features identifies a patient
      who may have an underlying systemic autoimmune disorder.

PMID- 12063488
TI  - Efficacy of the 308-nm excimer laser for treatment of psoriasis: results of a
      multicenter study.
AB  - OBJECTIVE: Our purpose was to demonstrate the efficacy of the 308-nm excimer
      laser for treatment of psoriasis. METHODS: This study was a multicenter open
      trial from 5 dermatology practices (one university-based and 4 private
      practices). Up to 30 patients per center with stable mild to moderate plaque-type
      psoriasis constituted the study population. Patients received 308-nm ultraviolet
      B doses to affected areas. The initial dose was based on multiples of a
      predetermined minimal erythema dose. Subsequent doses were based on the response
      to treatment. Treatments were scheduled twice weekly for a total of 10
      treatments. The main outcome measure was 75% clearing of the target plaque. Time
      to clearing was analyzed by Kaplan-Meier methods, accounting for truncated
      observations. RESULTS: One hundred twenty-four patients were enrolled in the
      study, and 80 completed the entire protocol. The most common reason for exiting
      from the study was noncompliance. Of the patients who met the protocol
      requirements of 10 treatments or clearing, 72% (66/92) achieved at least 75%
      clearing in an average of 6.2 treatments. Eighty-four percent of patients (95%
      confidence interval [CI], 79%-87%) reached improvement of 75% or better after 10
      or fewer treatments. Fifty percent of patients (95% CI, 35%-61%) reached
      improvement of 90% or better after 10 or fewer treatments. Common side effects
      included erythema, blisters, hyperpigmentation, and erosions, but they were well
      tolerated. CONCLUSIONS: Monochromatic 308-nm excimer laser treatment appears to
      be effective and safe for psoriasis. It requires fewer patient visits than
      conventional phototherapy, and, unlike those treatments, the laser targets only
      the affected areas of the skin, sparing the surrounding uninvolved skin.

PMID- 12063489
TI  - Combination of calcipotriene (Dovonex) ointment and tazarotene (Tazorac) gel
      versus clobetasol ointment in the treatment of plaque psoriasis: a pilot study.
AB  - BACKGROUND: Both calcipotriene and tazarotene have been shown to be effective in
      the treatment of psoriasis. No study has evaluated the effect of using both
      agents simultaneously. OBJECTIVE: Our purpose was to evaluate the effectiveness
      of combination treatment of psoriasis with calcipotriene ointment and tazarotene
      gel by comparing them with clobetasol ointment, a class I topical corticosteroid.
      A secondary objective was to evaluate the clinical compatibility of applying both
      agents at the same time. METHODS: This pilot study was a prospective, single
      center, open-label, right/left comparison of 28 lesion pairs in 15 patients. It
      consisted of a 2-week treatment phase, followed by a 4-week post-treatment
      observation phase. RESULTS: All 15 patients completed the treatment phase of the
      study. At the end of the active treatment phase (end of week 2), calcipotriene-
      and tazarotene-treated lesions showed nearly identical reductions in scaling (P
      =.93), plaque elevation (P =.76), and overall lesional severity scores (P =.29)
      compared with their matched clobetasol-treated counterparts. Erythema improved
      significantly more in clobetasol-treated lesions (P <.05) during the treatment
      period, but differences became statistically insignificant during the post
      treatment period (;P =.20). No patients had significant irritation from the
      treatments. During the post-treatment phase (weeks 3-6), all lesions worsened;
      plaque elevation returned somewhat more rapidly in calcipotriene- and tazarotene
      treated lesions (P <.01), whereas changes in scaling, erythema, and overall
      lesional severity were not significantly different between the two treatment
      groups (P >.05). CONCLUSION: The nonsteroid combination of twice-daily
      calcipotriene ointment and once-daily tazarotene gel was not statistically
      different from twice-daily application of the class I corticosteroid clobetasol
      ointment in reducing psoriatic scaling, plaque elevation, and overall lesional
      severity over a 2-week period. There does not seem to be any chemical
      incompatibility between calcipotriene ointment and tazarotene gel that is
      clinically significant.

PMID- 12063490
TI  - Recurrent polymorphous sweat gland carcinoma of the skin.
AB  - Polymorphous sweat gland carcinoma is an unusual, recently described variant of
      low-grade malignant adnexal neoplasm of the skin characterized by a prolonged
      clinical course and predilection for the extremities. We describe a case of
      recurrent polymorphous sweat gland carcinoma in a 56-year-old man who presented
      with multiple large skin nodules distributed along the flexor surface of his left
      arm. The lesions were treated by surgical excision; multiple local recurrences,
      as well as the development of new lesions, were observed over a period of 5
      years. No distant metastases have been observed so far. The clinical differential
      diagnosis and management of these unusual lesions are discussed.

PMID- 12063491
TI  - Oral contraceptive efficacy and antibiotic interaction: a myth debunked.
AB  - The purpose of this study was to review the pharmacokinetic and clinical
      literature regarding the efficacy of oral contraceptives when used concomitantly
      with antibiotic therapy. Relevant literature was identified by searching MEDLINE
      and EMBASE. Other sources were located by consulting the bibliographies of the
      material collected from MEDLINE and EMBASE. Pharmacokinetic evidence demonstrates
      that plasma levels of oral contraceptive steroids are unchanged with the
      concomitant administration of antibiotics, including ampicillin, ciprofloxacin,
      clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin,
      temafloxacin, and tetracycline. However, reduced steroid levels have been
      reported in women taking rifampin with oral contraceptives. Clinical reports of
      contraceptive failure with antibiotic use are retrospective, have multiple
      potential biases, and are not supported by pharmacokinetic data. Available
      scientific and pharmacokinetic data do not support the hypothesis that
      antibiotics (with the exception of rifampin) lower the contraceptive efficacy of
      oral contraceptives.

PMID- 12063493
TI  - The history of phototherapy: something new under the sun?
AB  - Phototherapy has a very long, albeit mostly anecdotal history. Real interest in
      the use of ultraviolet irradiation in the treatment of various diseases started
      in the 19th century and reached a climax when Niels Finsen received the Nobel
      Prize in 1903 for his therapeutic results with lupus vulgaris. This marked the
      start of modern phototherapy. It was used in thermal stations for treatment of
      tuberculosis, in the treatment of leg ulcers in wartime, and in the treatment of
      skin diseases. This article reviews the history of a treatment modality that
      greatly changed modern dermatologic treatment, although it is as old as mankind.

PMID- 12063492
TI  - Fur-rubbing behavior of capuchin monkeys.

PMID- 12063494
TI  - Surgical pearl: the use of the Ultra-Fine II short needle 0.3-cc insulin syringe
      for botulinum toxin injections.

PMID- 12063495
TI  - Sinus pericranii: dermatologic considerations and literature review.
AB  - Sinus pericranii is a rare disorder characterized by a congenital or acquired
      epicranial blood-filled nodule of the scalp that is in communication with an
      intracranial dural sinus through dilated diploic veins of the skull. We describe
      two patients with sinus pericranii: a 3-year-old boy with a congenital lesion and
      a 3-year-old girl whose lesion appeared after head trauma. We discuss the
      clinical presentation, dermatologic manifestations, differential diagnosis, and
      management as described in the available published literature. Patients with
      sinus pericranii may be brought to the attention of dermatologists and
      dermatopathologists because of skin changes in the scalp or forehead. The
      diagnosis is difficult to make clinically, because the skin manifestations are
      highly variable and may resemble other disorders of the scalp and cranium. The
      potentially lethal complications including hemorrhage, infection, and air
      embolism warrant a high index of suspicion for sinus pericranii.

PMID- 12063496
TI  - Chronic pigmented purpura associated with odontogenic infection.
AB  - Five patients with chronic pigmented purpura associated with odontogenic
      infection are described. Four patients had Schamberg's disease, and one had
      itching purpura. These patients were resistant to topical corticosteroid
      treatment, but appearance of purpuric spots ceased after treatment for
      periodontitis, pulpitis, or both. No circulating immune complexes were detected,
      and neither immunoglobulin nor complement was deposited in the papillary vessels
      of the skin. Odontogenic infection might be one of the precipitating factors for
      chronic pigmented purpura.

PMID- 12063497
TI  - Amphotericin B-resistant Aspergillus flavus infection successfully treated with
      caspofungin, a novel antifungal agent.
AB  - Invasive aspergillosis is uncommon in immunocompetent hosts but is the second
      most common opportunistic fungal infection in immunocompromised patients. There
      has been a dramatic increase in the incidence of life-threatening aspergillosis
      during the past 2 decades, and the morbidity and mortality of these infections
      despite antifungal therapy remain unacceptably high. We describe a patient with
      amphotericin B-resistant Aspergillus flavus successfully treated with
      caspofungin, an agent belonging to a new class of antifungal drugs. Caspofungin
      shows great promise in the treatment of invasive aspergillosis.

PMID- 12063498
TI  - The granuloma annulare phenotype and tuberculosis.
AB  - At one time it was believed that granuloma annulare was associated with or even
      caused by tuberculosis. In the past 50 years, that idea has seemed to be of
      little more than historic importance. A case is reported of chronic, inadequately
      treated tuberculosis with erythema induratum in which clinical and histologic
      lesions compatible with granuloma annulare occurred. Specific antituberculosis
      therapy caused clearing of the skin lesions. The previous reported cases of
      granuloma annulare and tuberculosis are summarized. Other systemic diseases
      reportedly associated with granuloma annulare are noted to emphasize the many
      possible etiologic relationships. Granuloma annulare may be viewed not as a
      disease sui generis but as a phenotypic macrophage-granulomatous response to
      multiple etiologic disease patterns.

PMID- 12063499
TI  - Adult acral cutaneous myofibromas in a patient with generalized morphea.
AB  - Myofibroma is the term for a group of solitary or generalized soft tissue tumors
      that may be located in the skin or within skeletal muscle, bone, and viscera.
      These tumors occur most commonly in children. However, examples of myofibroma
      have been reported in adults, in whom they usually present as solitary lesions of
      the head and neck, trunk, and extremities. "Cutaneous nodules" have been reported
      in both localized and systemic scleroderma, but to our knowledge, there are no
      specific reports of myofibromas developing in this patient population. We report
      a case of acral myofibromas in a patient with generalized cutaneous morphea. This
      occurrence is of interest in view of the possible role of myofibroblasts in the
      pathogenesis of scleroderma.

PMID- 12063500
TI  - Clinically and dermoscopically featureless melanoma: when prevention fails.
AB  - We report a case of amelanotic melanoma that was clinically and dermoscopically
      featureless; it was repeatedly missed during examination at a pigmented lesion
      clinic. Dermoscopy evidenced a peculiar vascular pattern, and only the adoption
      of a specific diagnostic algorithm including the atypical vascular pattern among
      the major diagnostic criteria would have helped the observer make the correct
      diagnosis. The risk of false-negative diagnosis by both clinical examination and
      dermoscopy during melanoma screening as well as the possible role of dermoscopy
      in the diagnosis of amelanotic melanoma are discussed.

PMID- 12063501
TI  - Erythrodermic psoriasis precipitated by radiologic contrast media.

PMID- 12063502
TI  - A comment on dressings for the recipient area of split-thickness skin grafts in
      vitiligo.

PMID- 12063503
TI  - Neutrophilic dermatosis of the dorsal hands versus pustular vasculitis.

PMID- 12063504
TI  - Vitiligo treated with topical corticosteroids: children with head and neck
      involvement respond well.

PMID- 12063505
TI  - A case of acrodermatitis enteropathica-like dermatosis caused by ornithine
      transcarbamylase deficiency.

PMID- 12063506
TI  - Altering the course of asthma: Introduction.

PMID- 12063507
TI  - Issues in understanding pediatric asthma: epidemiology and genetics.
AB  - Asthma is a heterogeneous disease characterized by varying phenotypes. Ongoing
      research is focused on identifying which children who have wheezing early will
      progress to childhood asthma. Genetic factors, predominantly atopy and a parental
      history of asthma as well as environmental stimuli, are key components in the
      development of asthma. Investigation into immunologic processes indicates that
      atopic children may have a cytokine imbalance or dysregulation in which the
      transition from T helper 2 (T(H)2)-type to T(H)1-type immunity is delayed.
      Several risk factors have been identified in the pathophysiology of asthma,
      including sensitization and exposure to cockroaches, house dust mites, and the
      mold Alternaria alternata, among other aeroallergens. Viral respiratory
      infections, primarily those caused by respiratory syncytial virus, are a
      significant risk factor for the development of childhood wheezing in the first
      decade of life. A number of prospective epidemiologic studies are investigating,
      among other issues, the relations among cytokine dysregulation, respiratory tract
      infections, and allergen exposure and sensitization in the development of asthma.
      Identifying the pathogenic mechanisms should enable clinicians to identify
      children at high risk and thereby to treat childhood asthma more effectively.

PMID- 12063508
TI  - Environmental factors influencing the development and progression of pediatric
      asthma.
AB  - Recent data underscore the importance of environmental factors in the
      sensitization of children to certain allergens and the development of asthma.
      Maternal smoking and family (especially maternal) history of atopy appear to be
      risk factors for persistent sensitization and development of asthma. Indeed,
      exposure to tobacco smoke in utero significantly increases asthma risk and
      influences the timing of sensitization. It must be stated that any smoking at
      home has consequences for the development of asthma and other respiratory
      conditions. In addition, reports of possible protective effects of specific
      environmental conditions suggest that exposure to certain stimuli may reduce or
      block the development and progression of asthma. Attendance at a day care center
      early in life appears to offer protective effects against wheezing, as do early
      episodes of rhinitis, herpes, and measles. Children raised on a farm also have a
      decreased prevalence of atopic diseases. The protective effect of contact with
      livestock and poultry is consistent among several studies. Although the
      pathophysiologic mechanisms involved remain undefined, studies suggest that
      exposure to endotoxin and other components of bacteria may play an important role
      in protecting against childhood atopic diseases. Whether in utero exposure is
      beneficial remains to be determined.

PMID- 12063509
TI  - Challenges to treatment goals and outcomes in pediatric asthma.
AB  - To achieve long-term control in pediatric asthma, it is essential to establish
      treatment goals acceptable to both the patient and care giver and to choose
      appropriate outcome measures that will show the benefits of the treatment.
      Differences between the perceptions of patients and care givers of what
      constitutes a desirable treatment goal, and poor perception of asthma control by
      both patient and physician, hinder optimal treatment of asthma. The use of
      objective outcome measures in pediatric asthma generally can provide a good
      evaluation of asthma severity as well as a basis for setting treatment goals that
      are acceptable to patients and care givers alike. Objective measurements that
      assess airway inflammation, which is the fundamental pathophysiology in asthma
      and the underlying mechanism for chronic airway remodeling, may be the most
      useful means for gauging pediatric asthma control and evaluating response to
      treatment. Techniques such as exhaled nitric oxide analysis, bronchoalveolar
      lavage, and sputum analysis, although used primarily in research, have
      successfully identified the level of airway inflammation in children.
      Furthermore, the association of meaningful outcome measures with education about
      the long-term effects of uncontrolled asthma and the need for anti-inflammatory
      treatment should help in developing treatment goals and strategies that will be
      acceptable to both patient and care giver.

PMID- 12063510
TI  - Airway inflammation in asthma and its consequences: implications for treatment in
      children and adults.
AB  - The development and wide availability of novel research techniques such as
      bronchoscopy and induced sputum have enhanced our understanding of the
      pathophysiology of asthma. The appreciation of the inflammatory nature of asthma
      and the remodeling associated with chronic disease have undoubtedly led to
      improved disease management and a better understanding of how anti-asthma drugs
      work. Although extensive data about inflammation and its sequelae in children are
      lacking, both chronic inflammation and airway remodeling are more than likely to
      be involved in the development and progression of asthma in this young
      population. Indeed, evidence suggests that airway restructuring occurs early. The
      implications for treatment in any differences of inflammation and remodeling
      between children and adults, then, are likely to be important. Although
      corticosteroids are considered as first-line anti-inflammatory treatment,
      especially in chronic asthma, for many patients neither inhaled nor oral
      corticosteroid therapy can control inflammation adequately. In children, neither
      the addition of long-acting beta(2)-agonist therapy nor doubling of the
      corticosteroid dose has produced the same benefits seen in adults. A clearer
      understanding of the pathophysiologic mechanisms of asthma in adults and
      pediatric patients should provide new insights into different asthma phenotypes.
      Therefore, the development and application of relatively simple and safe methods
      for assessing markers of inflammation and alterations in the airways are vital,
      especially for children.

PMID- 12063511
TI  - The natural history of asthma and early intervention.
AB  - The understanding of the natural history of asthma has changed significantly
      during the last 4 decades, with the view that asthma is a disease of chronic
      inflammation and varying degrees of severity replacing that of it being a disease
      of reversible airway obstruction. Treatment has progressed in accordance with the
      growing knowledge about the pathophysiologic mechanisms of asthma. Nevertheless,
      much remains unknown, especially about how to treat asthma effectively.
      Pharmacogenetics, an emerging field in which the knowledge of the genetic basis
      of a disease is applied to its treatment, may ultimately lead investigators to
      define many unanswered questions about asthma therapy. Asthma occurs early in
      childhood, but the ideal time for intervention and the most effective treatment
      strategy are yet unknown for young patients. The lack of response to a therapy
      may indicate the course of the disease as much as a lack of treatment efficacy.
      It may be that including such variables as airway hyperresponsiveness in
      treatment goals will not only become routine but will result in improved long
      term asthma treatment as well. The progress in defining asthma and targeting
      treatment toward specific pathophysiologic mechanisms should lead to better
      defined optimal strategies for treating asthma in children.

PMID- 12063512
TI  - Overcoming barriers to nonadherence in asthma treatment.
AB  - Inadequate patient adherence to prescribed treatment regimens is a major cause of
      poor clinical outcomes in the treatment of asthma. Among children with asthma,
      adherence rates are often below 50%. Multiple treatment-, clinician-, and patient
      related barriers prevent the achievement of satisfactory levels of adherence.
      Treatment-related barriers include prolonged and complex regimens, adverse
      effects, cost, and delayed onset of action. Clinician-related barriers include
      difficulty in scheduling, treatment by one different care giver after another,
      perceived clinician disinterest, and time constraints. Patient-related barriers
      include mild or severe asthma, poor understanding of the need for treatment,
      insufficient confidence in the clinician or medication, the presence of
      psychological problems, and low motivation to change behavior. Although all of
      these factors must be addressed to maximize adherence, patient motivation may be
      the most critical. This task falls primarily to clinicians (physicians, nurses,
      staff), and it requires thorough patient and care giver education, more frequent
      patient contact, and the development of a patient-clinician partnership dedicated
      to the effective treatment of asthma.

PMID- 12063513
TI  - Balancing safety and efficacy in the treatment of pediatric asthma.
AB  - The treatment of pediatric asthma requires balancing the efficacy and safety of
      various asthma medications, facilitating patient and family education, and
      developing a supportive treatment network. The efficacy and safety of the major
      asthma controllers--cromolyn, long-acting beta(2)-agonists, inhaled
      corticosteroids, and leukotriene receptor antagonists-are well tolerated overall
      when used appropriately. Cromolyn is used often as first-line therapy in treating
      pediatric asthma, but the inhaled corticosteroids remain the cornerstone of
      pediatric asthma control. Long-acting beta(2)-agonists are most beneficial when
      used intermittently or in combination with other asthma medications. The most
      recent class of drugs, the leukotriene receptor antagonists are effective in
      controlling asthma and are well tolerated in children as young as 2 years of age.
      In moderate-to-severe pediatric asthma, combination therapy is often required to
      achieve optimal asthma control. Leukotriene receptor antagonists combined with
      inhaled corticosteroids reduce the need for steroid rescue, the rate of serious
      exacerbations, and the level of inflammation. The treatment of asthma requires
      the ability to diagnose and treat asthma effectively. In subpopulations with
      special needs such as very young or inner-city minority children, treating asthma
      requires a comprehensive approach that includes a supportive patient-physician
      relationship and the involvement of schools, churches, and neighborhood outreach
      programs that will identify children with asthma and promote quality care.

PMID- 12063515
TI  - Airborne pollen: a brief life.
AB  - The transfer of pollen, whether it is transported by insects or carried by the
      wind, from floral anther to recipient stigma is the critical reproductive event
      among higher plants. In this scenario, the pollen grain functions as a fully
      constituted life-cycle stage, capable of growth (albeit limited) and delivery of
      gametes. Pollen is prepared for this role by an intricate developmental process
      with dual sources of structural elements and chemical constituents, including
      allergens. The resulting complexity relates, at least in part, to the
      requirements of an unforgiving recognition process at stigmatic surfaces and of
      active growth before the achievement of gametic union. Recently, the basic
      participants in pollen-stigma interactions have been defined, and they provide a
      striking counterpoint to human histocompatibility concerns. Pollen development
      offers a useful tableau in terms of which to reexamine forces affecting pollen
      prevalence and their interactions. Development also provides clues to the sources
      and significance of more minute bioaerosols now known to carry pollen allergens.

PMID- 12063516
TI  - T-cell activation through the antigen receptor. Part 2: role of signaling
      cascades in T-cell differentiation, anergy, immune senescence, and development of
      immunotherapy.
AB  - Part 2 of this review on cellular activation by the T-cell antigen receptor (TCR)
      will highlight how TCR signaling pathways are adapted to achieve specific
      biologic outcomes, including different states of T-cell differentiation and the
      induction of T-cell tolerance. We will also explore how treatment with altered
      peptide ligands affects TCR signaling to change T-cell differentiation or to
      induce an anergy state. These changes are accomplished through alteration of
      protein tyrosine kinase activity, the stoichiometry of phosphorylation of
      immunoreceptor tyrosine-based activation motifs, intracellular free ionized
      calcium flux, mitogen-activated protein kinase activity, and transcriptional
      activation of key cytokine promoters. The CTLA-4 plays an important role in the
      induction and maintenance of anergy. The second theme will highlight how altered
      TCR signal transduction, including changes in the compartmentalization of
      signaling components at the TCR synapse, contributes to decreased T-cell
      activation during immune senescence. Finally, we will illustrate how the
      molecular details of TCR activation can be used to modify the function of the
      immune system. This includes a description of the mechanism of action of altered
      peptide ligands, CTLA-4Ig, and pharmacologic inhibitors of mitogen-activated
      protein kinases, nuclear factor kappaB, and protein kinase C cascades.

PMID- 12063517
TI  - "Step-down" therapy for asthma: why, when, and how?

PMID- 12063518
TI  - Food manufacturing and the allergic consumer: accidents waiting to happen.

PMID- 12063519
TI  - Maternal stress and T-cell differentiation of the developing immune system:
      possible implications for the development of asthma and atopy.
AB  - The constant increase in asthma and atopy prevalences--despite improved treatment
      and knowledge of many aspects of the diseases--has raised growing concern.
      Accumulating evidence suggests that these increases in atopic diseases are
      largely attributable to environmental and lifestyle factors, and the lack of
      systemic childhood infections has in many studies emerged as a major factor. In
      addition to current high standards of hygiene and the lack or scarcity of such
      infections, another factor characteristic of our present-day lives could be
      involved. This review briefly outlines the possibility that prolonged maternal
      stress associated with sustained excessive cortisol secretion could affect the
      developing immune system--especially T(H)1/T(H)2 cell differentiation--and
      further increase the susceptibility to asthma and atopy in genetically
      predisposed individuals. This hypothesis is critically evaluated in the light of
      current knowledge.

PMID- 12063520
TI  - Step-down therapy with low-dose fluticasone-salmeterol combination or medium-dose
      hydrofluoroalkane 134a-beclomethasone alone.
AB  - BACKGROUND: Options for step-down therapy include use of inhaled corticosteroids
      alone or in combination with a long-acting beta2-agonist. OBJECTIVE: We sought to
      evaluate step-down therapy with a fluticasone propionate-salmeterol (FP-SM)
      combination administered through a dry powder inhaler (DPI; Advair Diskus) versus
      a medium dose of hydrofluoroalkane 143a-beclomethasone dipropionate (HFA-BDP)
      administered through a breath-actuated pressurized metered-dose inhaler (QVAR
      Autohaler). METHODS: Thirty-nine patients with uncontrolled moderate-to-severe
      asthma were treated with 1000 microg of DPI-administered BDP twice daily (DPI
      BDP) for 4 weeks and then randomized to 200 microg of HFA-BDP twice daily (n =
      20) or 100 microg of FP and 50 microg of SM twice daily (FM-SM; n = 19) for 8
      weeks in a double-blind, double-dummy, parallel-group design. We measured the
      provocative dose of methacholine producing a 20% fall in FEV1 (methacholine PD20)
      as the primary outcome, with secondary outcomes being lung function, surrogate
      inflammatory markers, diary card responses, quality of life, and safety. RESULTS:
      There was a 0.9 (95% confidence interval, 0.5-1.2) doubling dose improvement in
      methacholine PD20 comparing asthma before versus after DPI-BDP. HFA-BDP
      maintained this improvement, whereas FP-SM produced a further significant
      improvement, amounting to a 1.1 (95% confidence interval, 0.2-2.1) doubling dose
      difference at 8 weeks for FP-SM versus HFA-BDP. Effects on FEV1, peak expiratory
      flow, and quality of life (symptoms and emotions) were similar to those on
      methacholine PD20, with a significant difference between FP-SM and HFA-BDP.
      Suppression of plasma and urinary cortisol and serum osteocalcin levels occurred
      with DPI-BDP, but values returned to baseline levels within 1 month of HFA-BDP or
      FP-SM administration. CONCLUSION: After high-dose inhaled corticosteroid,
      stepping down with the combination inhaler conferred further improvements in
      bronchoprotection, bronchodilatation, and clinical control, but not inflammatory
      markers, compared with that seen with a medium dose of inhaled corticosteroid.

PMID- 12063521
TI  - Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin
      induced asthma.
AB  - BACKGROUND: The A to C transversion in the promoter region of the gene encoding
      leukotriene C4 synthase (LTC4S) is proposed to be associated with the development
      of aspirin-induced asthma (AIA). OBJECTIVE: We investigated the frequency of the
      polymorphism in Japanese population and its association with clinical
      characteristics and cysteinyl leukotriene production. METHODS: Genotyping of
      LTC4S gene promoter was performed on 60 patients with AIA, 100 patients with
      aspirin-tolerant asthma (ATA), and 110 control subjects. We assessed the basal
      levels of urinary LTE4, the increment of urinary LTE4 on venous aspirin
      challenge, and LTC4S activity in peripheral blood eosinophils. RESULTS: The
      frequency of the variant C allele was significantly higher in patients with AIA
      (frequency of allele [q] = 0.192) than in patients with ATA (q = 0.110, P =.042).
      Variant C-allelic carriers experienced asthma at a significantly younger age
      (31.8 +/- 2.9 years [mean +/- SEM]) than wild-type A homozygotes (41.3 +/- 2.2
      years, P =.007). Basal levels of LTE4 and the increment of urinary LTE4 on venous
      aspirin challenge did not show a difference between wild-type A homozygotes and
      variant C-allelic carriers. There was no relationship between the polymorphism
      and the LTC4S activity in eosinophils, although LTC4S activities were
      significantly higher in patients with AIA than in patients with ATA. CONCLUSION:
      Our findings reveal the lack of functionality of the polymorphism in the LTC4S
      gene, whereas this polymorphism might have some effect on the development of AIA,
      probably in linkage disequilibrium with another causatively important mutation.

PMID- 12063522
TI  - Allergen vaccination with a liposome-encapsulated extract of Dermatophagoides
      pteronyssinus: a randomized, double-blind, placebo-controlled trial in asthmatic
      patients.
AB  - BACKGROUND: Liposomes are potent immunologic adjuvants and have been proposed as
      allergen carriers in allergy vaccination. OBJECTIVE: We sought to investigate the
      efficacy and safety of vaccination with Dermatophagoides pteronyssinus
      encapsulated in liposomes. METHODS: We conducted a double-blind, placebo
      controlled study. Fifty-five asthmatic patients sensitized to mites were randomly
      assigned vaccination with D pteronyssinus extract encapsulated in liposomes or
      empty liposomes for a period of 12 months. The principal parameters were symptom
      and medication-consumption scores. The percentage of healthy days (ie, days
      without medication and with absent or mild symptoms) was calculated. Immediate
      and late skin test results, allergen bronchial challenge test results, and
      allergen-specific serum immunoglobulin levels were evaluated before and after
      treatment. RESULTS: All clinical scores were markedly lower in the active group
      than in the placebo group after vaccination. Nearly half (45.8%) of the patients
      actively treated reduced their symptom and medication scores by at least 60%
      versus only 12% of patients receiving placebo treatment (P =.0388). The
      percentage of healthy days in the active group rose from 10.5% before treatment
      to 64.5% afterward (P =.0008). Reduction in organ sensitivity was demonstrated by
      skin prick test responses (P <.01), late-phase response after intradermal testing
      (P =.009), and bronchial challenge test results (P =.026) in the active group.
      Serum levels of specific IgG increased throughout the treatment, whereas specific
      IgE levels showed only an initial transient increase. No change in these
      parameters was observed in the placebo group. Vaccination was well tolerated, and
      no subcutaneous nodules appeared. CONCLUSION: Vaccination with D pteronyssinus
      encapsulated in liposomes is an effective and safe treatment for allergy-induced
      asthma.

PMID- 12063523
TI  - Comparison of a nasal glucocorticoid, antileukotriene, and a combination of
      antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis requires active intervention for symptom relief. A
      combination of antileukotriene and antihistamine drugs has been suggested to
      provide additive treatment benefits for patients with allergic rhinitis.
      OBJECTIVE: We evaluated how such a combination treatment would affect symptoms
      and local mucosal eosinophilia in comparison with a nasal glucocorticoid.
      METHODS: In a double-blind, randomized study 62 patients with grass pollen
      induced allergic rhinitis received a nasal glucocorticoid (fluticasone propionate
      aqueous nasal spray [FPANS], 200 microg/d), an antileukotriene (montelukast, 10
      mg/d), a combination of montelukast with an antihistamine (loratadine, 10 mg/d),
      or placebo throughout the season. Cromoglycate eyedrops and a limited amount of
      loratadine were allowed as rescue medication for severe symptoms. Patients
      recorded their symptoms for nasal blockage, itching, rhinorrhea, and sneezing.
      Before and during the season, nasal biopsy specimens were obtained from patients
      for evaluation of local eosinophilic inflammation. RESULTS: During the peak
      season, both FPANS and combined montelukast-loratadine were significantly more
      effective than placebo and montelukast alone for daytime symptom prevention. For
      nighttime symptoms, FPANS was significantly more effective compared with all
      other treatments, whereas combined montelukast-loratadine and montelukast alone
      did not provide significant symptom prevention compared with placebo. The pollen
      induced increase in the numbers of epithelial eosinophils was significantly lower
      for FPANS-treated patients compared with that seen in all other treatment groups.
      CONCLUSION: In patients with seasonal allergic rhinitis, intranasal
      glucocorticoids are more effective than an antileukotriene drug or combined
      antileukotriene-antihistamine for the reduction of pollen-induced nasal
      eosinophilic inflammation and for control of nasal symptoms.

PMID- 12063525
TI  - Effect of continuing or finishing high-level sports on airway inflammation,
      bronchial hyperresponsiveness, and asthma: a 5-year prospective follow-up study
      of 42 highly trained swimmers.
AB  - BACKGROUND: Mild eosinophilic airway inflammation and bronchial
      hyperresponsiveness-ie, mild asthma-have been shown to affect a high proportion
      of endurance athletes. The persistence of airway inflammation, bronchial
      hyperresponsiveness, and asthma in this population is not known, however,
      inasmuch as follow-up studies of athletes' asthma have not been performed.
      OBJECTIVE: The purpose of this study was to investigate effect of finishing high
      level sports on airway inflammation, bronchial hyperresponsiveness, and asthma.
      METHODS: Forty-two elite competitive swimmers, most of them from the Finnish
      national team (37/42; 88%), were followed for 5 years in a prospective manner.
      All of the swimmers completed questionnaires and underwent resting spirometry,
      histamine challenge testing, and skin prick tests at baseline and at follow-up.
      Twenty-nine swimmers (69%) also gave induced sputum samples on both occasions.
      Sixteen (38%) of the swimmers had continued their competitive careers during
      follow-up (active swimmers), but 26 (62%) had stopped competing more than 3
      months before the follow-up examination (past swimmers). RESULTS: Bronchial
      responsiveness was increased in 7 (44%) of the 16 active swimmers at baseline and
      in 8 (50%) of the 16 active swimmers at follow-up; it was increased in 8 (31%) of
      the 26 past swimmers at baseline and in 3 (12%) of the 26 past swimmers at follow
      up (McNemar test, P =.025). The difference in the change in bronchial
      hyperresponsiveness between the study groups was significant (likelihood ratio
      test, P =.023). Current asthma (defined as bronchial hyperresponsiveness and
      exercise-induced bronchial symptoms monthly) was observed in 5 (31%) of the
      active swimmers at baseline and in 7 (44%) of the active swimmers at follow-up;
      of the past swimmers, it occurred in 6 (23%) at baseline and in 1 (4%) at follow
      up (McNemar test, P =.025). The difference in the change in current asthma
      between the study groups was significant (likelihood ratio test, P =.0040). The
      sputum differential cell counts of eosinophils and lymphocytes increased
      significantly during the follow-up period in the active swimmers (Wilcoxon signed
      rank sum test; P =.033 and P =.0029, respectively); in the past swimmers, the
      sputum differential cell counts of eosinophils tended to decrease during the
      follow-up period (P =.17), whereas the differential cell counts of lymphocytes
      did not change significantly. The changes in the sputum differential cell counts
      of eosinophils between the study groups differed significantly (Mann-Whitney U
      test, P =.019). CONCLUSION: In swimmers who had stopped high-level training,
      bronchial hyperresponsiveness and asthma attenuated or even disappeared. Mild
      eosinophilic airway inflammation was aggravated among highly trained swimmers who
      remained active during the 5-year follow-up. Our results suggest that athletes'
      asthma is partly reversible and that it may develop during and subside after an
      active sports career.

PMID- 12063524
TI  - Effect of desloratadine versus placebo on nasal airflow and subjective measures
      of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in
      an allergen-exposure unit.
AB  - BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion
      in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the
      effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms,
      including nasal congestion, in response to grass pollen in an allergen-exposure
      unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover
      trial, 47 subjects with histories of SAR received desloratadine or placebo every
      morning for 7 days and, after a 10-day washout period, were crossed over to the
      other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on
      day 7 of each treatment period. Nasal airflow and nasal secretion weights were
      measured before and every 30 minutes during allergen exposure; SAR symptoms
      (including nasal congestion) were scored before exposure and every 15 minutes
      thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less
      severe with desloratadine than with placebo (P <.02). Individual and combined SAR
      symptom severity scores, including nasal congestion and sneezing, were
      significantly lower with desloratadine than with placebo (all P < or =.003).
      Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P
      <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal
      congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine
      compared with placebo, and this continued throughout (0-6 hours) allergen
      exposure. Desloratadine was well tolerated, with an adverse event profile similar
      to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms,
      desloratadine significantly reduced the severity of nasal obstruction and
      accompanying complaints of nasal congestion and other SAR symptoms compared with
      the effects of placebo.

PMID- 12063526
TI  - Increase in the prevalence of allergen skin sensitization in successive birth
      cohorts.
AB  - BACKGROUND: Little is known about longitudinal trends in the prevalence of
      allergen skin sensitization in the general population. OBJECTIVE: We sought to
      measure the change in prevalence of allergen skin sensitization over a 9-year
      period in a cohort of adults and hence to determine whether cross-sectional
      differences in prevalence between age groups are due to an aging or cohort
      effect. METHODS: In 1991 and 2000, we measured skin sensitization, defined as a
      wheal diameter of 3 mm or larger than that elicited by a saline control, to
      Dermatophagoides pteronyssinus, cat fur, mixed grass, Aspergillus fumigatus, and
      Cladosporium herbarum in a cohort of 1339 adults from Nottingham aged between 18
      and 71 years in 1991. Subjects were divided into six 9-year successive birth
      cohorts, and the effects of birth cohort and the within-subject change from 1991
      to 2000 were analyzed in a generalized estimating equation logit model. RESULTS:
      The unadjusted prevalence of sensitization to any allergen was 30.5% in 1991 and
      31.8% in 2000. In cross-sectional analyses the prevalence of sensitization
      decreased with increasing age at both surveys (risk ratio, 2.15; 95% confidence
      interval [CI], 1.45-3.17 for 18- to 26-year-old patients relative to 63- to 70
      year-old patients in the 1991 survey). In longitudinal analysis there was no
      within-subject change in sensitization from 1991 to 2000 (adjusted odds ratio,
      1.07; 95% CI, 0.97-1.19), but there was a significant cohort effect (adjusted
      odds ratio per successive 9 year cohort, 1.27; 95% CI, 1.18-1.37). CONCLUSION:
      The cross-sectional decrease in allergen sensitization with age in the general
      population arises predominantly from a secular increase in sensitization
      prevalence with successive birth cohorts and not to a loss of sensitization
      within subjects over time. As a result of this cohort effect, the prevalence of
      allergic sensitization has increased in this general adult population sample.

PMID- 12063528
TI  - Upregulation of IL-13 concentration in vivo by the IL13 variant associated with
      bronchial asthma.
AB  - BACKGROUND: A substantial body of evidence exists to support the pivotal role of
      IL-13 in the pathogenesis of bronchial asthma. We recently found that a variant
      of the IL13 gene (Arg110Gln) is genetically associated with bronchial asthma,
      which is concordant with animal experiments using IL-13 in the development of
      asthma. OBJECTIVE: To address whether the Gln110 variant of IL13 influences IL-13
      function, contributing to the pathogenesis of bronchial asthma, we studied the
      functional properties of the variant. METHODS: We generated 2 types of
      recombinant IL-13 proteins, the amino acids of which at 110 were arginine or
      glutamine, and analyzed the binding affinities with the IL-13 receptors, as well
      as the stability of the proteins. We further compared the relationship between
      the genotype and serum levels of IL-13. RESULTS: The variant showed a lower
      affinity with the IL-13 receptor alpha2 chain, a decoy receptor, causing less
      clearance. The variant also demonstrated an enhanced stability in both human and
      mouse plasma. We further identified that asthmatic patients homozygous for the
      Gln110 variant have higher serum levels of IL-13 than those without the variant.
      CONCLUSION: These results suggested that the variant might act as a functional
      genetic factor of bronchial asthma with a unique mechanism to upregulate local
      and systemic IL-13 concentration in vivo.

PMID- 12063527
TI  - Cysteinyl leukotrienes induce IL-4 release from cord blood-derived human
      eosinophils.
AB  - BACKGROUND: Eosinophils contain preformed stores of IL-4 within their cytoplasmic
      granules, but physiologic stimuli to release IL-4 from eosinophils are not yet
      defined. OBJECTIVE: We evaluated whether cysteinyl leukotrienes (CysLTs) could
      elicit IL-4 release from eosinophils. METHODS: We used a dual-antibody capture
      and detection assay (EliCell) for IL-4 release and used eosinophils
      differentiated in vitro from human cord blood-derived progenitors. RESULTS:
      Leukotriene (LT) C4, LTD4, and LTE4 each elicited the rapid, vesicular transport
      mediated, dose- and time-dependent release of IL-4 from eosinophils. Both LTD4
      and LTE4 evoked similar and earlier IL-4 release than LTC4. LTC4 did not act
      directly but only after conversion to LTD4 because an inhibitor of gamma-glutamyl
      transpeptidase, acivicin, blocked LTC4-induced IL-4 release. MK571 and LY171833,
      receptor antagonists for CysLT1 and not CysLT2, and pertussis toxin inhibited
      LTC4-, LTD4-, and LTE4-induced IL-4 release. Cord blood-differentiated
      eosinophils contained CysLT1 protein detectable by means of immunoblotting.
      CONCLUSION: CysLTs acting through G(i) protein-coupled and MK571- and LY171833
      inhibitable receptors on cord blood-derived human eosinophils can act as
      autocrine or paracrine mediators to stimulate the rapid, nonexocytotic release of
      preformed IL-4.

PMID- 12063529
TI  - Transduction of dendritic cells by antigen-encoding lentiviral vectors permits
      antigen processing and MHC class I-dependent presentation.
AB  - BACKGROUND: Because antigen-presenting dendritic cells (DCs) play a major role in
      the polarization of T cells, including T(H)2 cells involved in allergy,
      strategies to modify DCs genetically are required. OBJECTIVE: The purpose of this
      investigation was to transduce murine bone marrow-derived DCs with lentiviral
      vectors encoding antigen to demonstrate antigen processing and MHC class I
      dependent presentation. METHODS: Bone marrow leukocytes were incubated with
      antigen-encoding lentiviral constructs and cultured with GM-CSF, IL-4, and Flt-3
      ligand. The capacity of the resulting DCs to express, process, and present
      antigen was tested in vitro. RESULTS: An average of 40% of DCs expressed antigen
      after 1 week of culture when antigen encoded by the lentiviral vector construct
      was green fluorescent protein. To demonstrate that transduced antigen can be
      presented by DCs on MHC class I, we chose the lymphocytic choriomeningitis virus
      glycoprotein (gp) as a model antigen, inasmuch as it is recognized by CD8 T cells
      from transgenic mice expressing an MHC class I-restricted T-cell receptor
      specific for the epitope of positions 33 through 41 of gp. DCs transduced with
      lentiviral construct encoding gp and matured with LPS activated transgenic T
      cells in an antigen-specific fashion. Using transporter associated with antigen
      presentation (TAP)-deficient mice, we show that presentation of the gp33-41
      epitope is TAP-dependent, confirming processing of gp by the endogenous pathway.
      CONCLUSIONS: These results demonstrate that CD8 T cells can recognize MHC class I
      epitopes processed from antigen in DCs transduced with lentiviral vectors.
      Lentiviral transduction of DCs and antigen presentation to CD8 T cells could be
      exploited for immunotherapy, because allergen-specific CD8 T cells have been
      shown to be suppressive in IgE-dependent allergy models.

PMID- 12063530
TI  - Does heparin prophylaxis prevent exacerbations of hereditary angioedema?
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare disorder characterized by
      episodes of angioedema of the skin, mucous membranes, and gastrointestinal tract
      resulting from a defect in the gene that produces C1 esterase inhibitor. Although
      in vitro laboratory data and past reports suggested that heparin might be
      efficacious in preventing HAE attacks, no controlled study has been reported to
      examine heparin's efficacy in this regard. OBJECTIVES: We sought to determine the
      safety and efficacy of inhaled and subcutaneous heparin versus that of placebo in
      the prevention of HAE attacks. METHODS: We performed a double-blind, double
      dummy, saline placebo-controlled, randomized, 3-way crossover study with 11
      visits. RESULTS: The study was designed to enroll 24 patients. Twenty-two
      patients were randomized and received the study drug. Patients did not have a
      significant decrease in average flare intensity after they received injected or
      inhaled heparin compared with that seen after placebo, the primary endpoint.
      However, when patients received injected heparin, they had a statistically
      significant decrease in average flare intensity compared with that seen with
      inhaled heparin after a normalizing transformation was applied. When the means
      are back transformed, this translates into median flare intensities of 9.2, 8.0,
      and 5.1 in the patients treated with inhaled heparin, placebo, and injected
      heparin, respectively. There were no significant differences when individual
      symptoms were examined, when total numbers of flares over a 6-week observation
      period were examined, or when global evaluations by the patients and
      investigators were evaluated. Adverse event severity was fairly uniform across
      treatments, with the majority of events classified as moderate and the remainder
      split between mild and severe. Injected heparin treatment was associated with
      higher rates of relatedness than other treatments, which was partially explained
      by 17 adverse events specifically related to the injection process itself
      (tenderness, bruising, redness, pain, and itching at the injection site). The
      injection treatment was also associated with a larger overall number of reported
      adverse events (70 vs 48 in the placebo treatment). Tenderness and bruising at
      the injection site were entirely confined to the injected heparin treatment.
      CONCLUSIONS: Injected and inhaled heparin failed to attenuate average flare
      intensity, the primary endpoint, compared with placebo. Interestingly, after
      patients injected heparin, they had a significant decrease in average flare
      intensity compared with that seen after inhalation of heparin. There were no
      differences among groups in other efficacy parameters. Taken together, these data
      indicate that commercial heparin was ineffective in preventing exacerbations of
      HAE.

PMID- 12063531
TI  - Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients
      with common variable immunodeficiency.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is a primary immune disorder
      characterized by antibody deficiency and a decrease in serum IgG and IgA, IgM, or
      both levels at least 2 SDs below the mean for age and not attributed to other
      known immunologic disorders. These patients often present with frequent and
      severe episodes of pneumonia before diagnosis. The standard treatment,
      intravenous immunoglobulin (IVIG), has been available for the past 20 years. No
      large-scale study has compared the incidence of pneumonia in these patients
      before and after IVIG treatment. OBJECTIVE: The aim of this study was to document
      the effectiveness of intravenous immunoglobulin treatment on the incidence of
      pneumonia in patients with CVID. METHODS: We performed chart reviews and
      interviews of patients with laboratory-confirmed CVID seen at our clinical
      center. The number of episodes of pneumonia was documented before and after
      treatment with immunoglobulin replacement therapy. RESULTS: The histories of 50
      patients were reviewed (mean current age, 42 +/- 16.3 years; age range, 10-78
      years; 20 male and 30 female patients). Forty-two (84%) of the 50 patients with
      CVID had pneumonia at least once before receiving immunoglobulin treatment, and
      11 of 42 of these patients had multiple episodes. After treatment with gamma
      globulin over a mean period of 6.6 +/- 5.2 years (range, <1-20 years), the number
      of patients experiencing pneumonia significantly decreased to 11 (22%) of 50. In
      most cases these patients had pneumonia in the first year of immunoglobulin
      treatment. CONCLUSION: The treatment of CVID with IVIG significantly reduces the
      incidence of pneumonia.

PMID- 12063532
TI  - Delayed-type hypersensitivity reaction to paraphenylenediamine is mediated by 2
      different pathways of antigen recognition by specific alphabeta human T-cell
      clones.
AB  - BACKGROUND: Allergic contact dermatitis to paraphenylenediamine (PPD) is a
      frequent cause of morbidity and occupational disability. OBJECTIVE: The aim of
      the study was to characterize T-cell responses to PPD and Bandrowski's base (BB),
      an autoxidation product of PPD, by using polyclonal and monoclonal T-lymphocyte
      cultures. METHODS: PPD- and BB-driven proliferation of PBMCs and T-cell clones
      (TCCs) was assessed by means of tritiated thymidine incorporation. Surface
      markers were studied by means of flow cytometry, and cytokine generation was
      assessed with an ELISA. RESULTS: TCCs, with one exception, were CD4+/CD45RO+, and
      T-cell receptors were alphabeta+. Three of 6 TCCs expressed Vbeta 16. TCC
      stimulation was HLA-DP restricted, and TCCs secreted IL-4, IL-5, and marginal
      levels of IFN-gamma. TCCs reacted to both PPD and BB. Presentation of BB to TCCs
      was dependent on viable antigen-presenting cells (APCs) pulsed for 4 hours, and
      fixed APCs failed to stimulate TCCs. Moreover, polyclonal responses to BB were
      enhanced by metabolically active enzymes, such as cytochrome P450 enzymes. BB has
      to be metabolized and processed. In contrast, fixation of APCs did not impair
      their ability to present PPD to TCC, whereas pulsing of APCs with PPD failed to
      stimulate TCCs. Thus PPD had to be present during the process, and polyclonal
      stimulation was not enhanced by cytochromes. CONCLUSION: These results suggest
      that PPD itself can be recognized by T cells through a processing-independent
      pathway, whereas its autoxidation product, BB, required processing and possibly
      metabolism to stimulate the same TCC. Our data demonstrate that 2 distinct
      pathways of antigen presentation to activate specific TCCs are involved in the
      immune response to PPD.

PMID- 12063533
TI  - Recognition of pathogenically relevant house dust mite hypersensitivity in adults
      with atopic dermatitis: a new approach?
AB  - BACKGROUND: The pathogenic importance of the ubiquitous house dust mite,
      Dermatophagoides pteronyssinus (Dp), in atopic dermatitis is unclear. OBJECTIVE:
      We aimed to explore the relevance of Dp hypersensitivity in adult patients with
      atopic dermatitis by using an in vivo topical challenge method and in vitro
      assays for T-cell reactivity. METHODS: Dp and control skin prick test solutions
      were applied to the cubital fossae of 20 patients twice daily for 4 days; the
      severity of dermatitis and pruritus in the challenge sites were determined before
      and after testing. The same solutions were used in PBMC proliferation assays that
      included 10% fresh, autologous serum, the latter aimed at maximizing IgE
      facilitated allergen presentation. RESULTS: Although most patients had markedly
      elevated Dp-specific serum IgE levels, only 6 of 20 patients developed increases
      in cubital fossa dermatitis severity and pruritus scores that were greater at
      sites of application of Dp solution than at control sites. In addition, PBMC
      proliferation in response to Dp solution in the presence of autologous serum was
      significantly greater in the in vivo challenge-positive patients than in those
      who did not respond to challenge. A subgroup of patients (7/20) also developed
      transient but pronounced contact urticaria at sites of Dp application.
      CONCLUSION: These findings suggest that hypersensitivity to Dp might be
      clinically relevant in approximately one third of the adult atopic dermatitis
      population studied. They also point to methods of identifying patients who might
      respond to house dust avoidance measures.

PMID- 12063534
TI  - Interpretation of commercial food ingredient labels by parents of food-allergic
      children.
AB  - BACKGROUND: To avoid allergic reactions, food-allergic consumers depend on the
      ingredient labels of commercial products. Complex ingredient terminology (eg,
      casein and whey for milk) and label ambiguities (eg, natural flavor and may
      contain peanut ) might compromise the ability of patients/parents to determine
      the safety of particular products. OBJECTIVE: The purpose of this investigation
      was to determine the accuracy of label reading among parents of food-allergic
      children. METHODS: Parents of children on restricted diets attending our referral
      center were asked to review a group of 23 food labels taken from widely available
      commercial products. For each label, each parent/parent pair was asked to
      indicate whether the product was safe for the allergic child and, if it was not,
      which foods restricted from the child's diet were in the product. RESULTS: There
      were 91 participants. Peanut was the most commonly restricted food (82 children),
      followed by milk, egg, soy, and wheat (60, 45, 27 and 16 children, respectively).
      Identification of milk and soy was the most problematic: only 4 (7%) of 60
      parents correctly identified all 14 labels that indicated milk, and only 6 (22%)
      of 27 parents correctly identified soy protein in 7 products. Peanut was
      correctly identified in 5 products by 44 (54%) of the 82 parents restricting
      peanut. Wheat (10 labels) and egg (7 labels) were correctly identified by most
      parents (14/16 and 42/45, respectively). Correct label identification was
      associated with prior instruction by a dietitian. CONCLUSIONS: With current
      labeling practices, most parents are unable to identify common allergenic food
      ingredients. These results strongly support the need for improved labeling with
      plain-English terminology and allergen warnings as well as the need for diligent
      education of patients about reading labels.

PMID- 12063535
TI  - Recalls of foods containing undeclared allergens reported to the US Food and Drug
      Administration, fiscal year 1999.
AB  - BACKGROUND: Food recalls can play a role in preventing or reducing the number of
      allergic reactions that may occur after a product containing an undeclared
      allergen has been introduced into commerce. OBJECTIVE: We sought to summarize the
      US Food and Drug Administration's records of recalls classified for fiscal year
      1999 involving foods containing undeclared allergens. METHODS: Food and Drug
      Administration food recall records were reviewed for fiscal year 1999 to identify
      recalls that occurred because of the undeclared presence of one or more of the
      following allergens: milk, eggs, fish, wheat, crustacean shellfish, tree nuts,
      peanuts, and soy. Each record was reviewed to determine the recalled product, the
      undeclared allergen present, the reason for recall, and reported adverse events.
      RESULTS: Of 659 total food products classified for recall during fiscal year
      1999, 236 (36%) products were recalled because they contained one or more
      undeclared allergens. Consumers were the party most often responsible for
      identifying that an undeclared allergen was present in a product (56% of recalled
      products). A total of 34 consumers reported allergic reactions after consumption
      of the recalled products. Three principal factors contributed to the presence of
      undeclared allergens in the recalled products: ingredient-statement omissions and
      errors (51% of all recalled products); manufacturing equipment cross-contact
      (40%); and errors by ingredient suppliers or manufacturing firm employees (5%).
      CONCLUSION: The presence of undeclared allergens in food products represents one
      of the more common reasons for food-product recall in the United States. A number
      of well-recognized allergens may be introduced into foods as a result of several
      different factors.

PMID- 12063536
TI  - Improved screening for peanut allergy by the combined use of skin prick tests and
      specific IgE assays.
AB  - BACKGROUND: The diagnosis of peanut allergy must be based on reliable, safe
      criteria. Double-blind, placebo-controlled food challenges (DBPCFCs) are the gold
      standard but are costly and dangerous because they can trigger severe reactions.
      OBJECTIVE: The aim of this study was to develop a new strategy for diagnosing
      peanut allergy while reducing the need for DBPCFCs. METHODS: We studied 363
      children referred for an evaluation of suspected food hypersensitivity. They all
      benefited from the same diagnostic strategy, which included, in order, clinical
      history, a skin prick test (SPT), and a specific IgE assay. DBPCFCs were
      performed on all the children by personnel who were unaware of the results of the
      other tests. To assess the performance characteristics of the SPT (comparing
      commercial and raw peanut extracts) and the specific IgE assay, we compared the
      results with those provided by the DBPCFCs. For SPTs and specific IgE assays, we
      sought to determine the cutoff values required to exclude false-positive and
      false-negative results. RESULTS: According to DBPCFC results, 177 children were
      allergic to peanut, and 186 were not. The performance characteristics of the SPTs
      were superior with the raw extract because the negative predictive value was 100%
      (95% confidence interval [CI], 97.5-100). If the skin reaction with the raw
      extract was less than 3 mm, we could be quite certain that the child was not
      allergic. On the other hand, if the SPT resulted in a wheal diameter of larger
      than 3 mm, we could only be 74% certain that the children were allergic.
      Furthermore, if the SPT resulted in a wheal diameter of 16 mm or larger, we could
      be quite certain that the child was allergic because the positive predictive
      value was 100% (95% CI, 86.8-100). Specific IgE concentrations of 57 kU(A)/L or
      greater were associated with a positive predictive value of 100% (95% CI, 87.2
      100). The combined use of the tests resulting in a positive diagnosis if the SPT
      result was 16 mm or larger or specific IgE concentration was 57 kU(A)/L or
      greater and in a negative diagnosis if the SPT result was less than 3 mm and the
      specific IgE concentration was less than 57 kU(A)/L allowed us to classify
      subjects with almost complete certainty as being allergic or not because the
      predictive values were 100%. CONCLUSION: Commercial extracts could not be used to
      reliably predict tolerance of peanut. Peanut DBPCFCs can be avoided when SPTs
      with raw extracts resulted in wheals with a largest diameter of less than 3 mm
      and a specific IgE concentration of less than 57 kU(A)/L and also when wheal
      diameters were 16 mm or larger or specific IgE values were 57 kU(A)/L or greater.
      Otherwise, DBPCFCs were indispensable for the unequivocal diagnosis of peanut
      allergy.

PMID- 12063537
TI  - Anaphylaxis to Russian Beluga caviar.

PMID- 12063538
TI  - Intestinal Bifidobacterium species induce varying cytokine production.

PMID- 12063539
TI  - Systemic availability of Rhinocort Aqua (budesonide) nasal spray: importance of
      formulation and definition of delivered dose.

PMID- 12063540
TI  - Glucocorticoids in herbal formulas?

PMID- 12063542
TI  - Quantitative and qualitative in vivo angiogenesis assay.
AB  - We describe the development and optimization of an in vivo angiogenesis assay
      utilizing gelfoam sponges impregnated with 0.4% agarose and different
      proangiogenic factors, such as basic fibroblast growth factor (bFGF), vascular
      epidermal growth factor (VEGF), tumor growth factor-alpha (TGF-alpha), and
      endothelial growth factor (EGF). The sponges are implanted into the subcutis of
      mice and harvested after different times. The gelfoam sponges are fixed,
      sectioned, and stained with fluorescent antibodies against CD31. The median
      number of CD31+ cells is determined in 10 different 0.159-mm2 fields.
      Proangiogenic molecules induced significant migration and proliferation of
      endothelial cells. To demonstrate the utility of this assay for evaluation of an
      antiangiogenic agent, mice were implanted with gelfoam sponges containing
      different proangiogenic factors and treated orally with water or PTK 787, a novel
      tyrosine kinase inhibitor with specific activity against the VEGF-R. PTK 787
      significantly inhibited angiogenesis in sponges containing agarose + VEGF but not
      other proangiogenic molecules. The data show that the implanted gelfoam sponges
      provide a reliable quantitative assay to study in vivo angiogenesis.

PMID- 12063543
TI  - EGFR antisense treatment of human HNSCC cell lines down-regulates VEGF expression
      and endothelial cell migration.
AB  - Overexpression of the epidermal growth factor receptor (EGFR) is thought to play
      a key role in the development of head and neck squamous cell carcinoma (HNSCC)
      primarily through its effect on promoting uncontrolled cell proliferation.
      Blocking EGFR ligand binding might also inhibit angiogenesis and down-regulate
      the production of angiogenic factors. Angiogenesis is increased in various human
      tumors, including head and neck squamous cell carcinoma (HNSCC), and correlates
      with tumor progression and metastasis. The vascular endothelial growth factor
      (VEGF) is thought to be the most important angiogenic factor. We determined
      whether VEGF antisense oligonucleotide treatment can decrease angiogenic activity
      of HNSCC cell lines in vitro. By using a 21-mer antisense phosphorothioate
      oligonucleotide targeting the translation start site of human EGFR mRNA, we
      examined modulation of VEGF expression in cell line supernatants by capture
      ELISA, and in cell lysates by Western blotting. Human umbilica vein endothelial
      cells (HUVEC) were grown in conditioned medium produced from the treated tumor
      cells. Endothelial cell migration was measured using a modified Boyden chamber.
      EGFR antisense oligonucleotide treatment resulted in a significant reduction of
      VEGF protein expression compared to sense oligonucleotide control. Addition of
      conditioned medium from EGFR antisense-treated tumor cells resulted in decreased
      endothelial cell migration. In conclusion, therapeutic strategies targeting EGFR
      signaling in head and neck cancer might have an antitumor effect mediated in part
      by inhibition of tumor angiogenesis.

PMID- 12063544
TI  - Establishment of a new human synovial sarcoma cell line, FU-SY-1, that expresses
      c-Met receptor and its ligand hepatocyte growth factor.
AB  - Only a small number of human synovial sarcoma cell lines have been reported, and
      of those, not all have been fully characterized, especially at the molecular
      level. We describe here the establishment and characterization of a new human
      cell line, FU-SY-1, which originated from a monophasic fibrous synovial sarcoma
      arising in the supinator muscle of a 31-year-old woman. This cell line propagated
      continuously in vitro for 73 serial passages for more than 36 months. FU-SY-1
      cells in vitro were rather small, exhibited a spindle or polygonal shape without
      conspicuous pleomorphism, and expressed c-Met and hepatocyte growth factor (HGF)
      as determined by immunocytochemistry. Cytogenetically, FU-SY-1 cells maintained a
      consistent karyotype: 47, X, +7, t(X;18)(p11.2;q11.2), the same as that of the
      original tumor specimen. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      demonstrated a SYT-SSX fusion transcript and expression of c-Met and HGF mRNA in
      FU-SY-1 cells. A subsequent sequence analysis using the PCR products confirmed
      that the detected messages were derived from the SYT-SSX1 fusion gene. This cell
      line, FU-SY-1, established from a monophasic fibrous synovial sarcoma, may
      therefore be a useful tool for investigation of the mechanisms of tumorigenesis
      and progression in human synovial sarcomas.

PMID- 12063545
TI  - Tumor cell specific expression of MMP-2 correlates with tumor vascularisation in
      breast cancer.
AB  - The metastatic potential of tumors is dependent on the ability of tumor cells to
      degrade extracellular matrix components by the expression of matrix
      metalloproteinases (MMPs) and to induce vascularisation of the tumor tissue.
      Thus, expression of MMPs and the number of blood vessel in tumor tissue may serve
      as prognostic markers of aggressive and metastasizing tumor growth. We have
      determined the vascularisation and the expression of MMP-2 by immuno
      histochemical staining of 19 benign and 75 malignant breast tissue specimens with
      CD31- and MMP-2 specific antisera. The degree of vascularisation was expressed by
      intratumoral microvascular density (IMD), which takes into account all vessels
      present in a hot spot irrespective of their size. In addition, we have introduced
      a novel parameter, vascular grading (VG), which describes the percentage of small
      microvessels of <20 microm in diameter in the total number of blood vessels. IMD
      tended to indicate an elevated risk for metastasis formation and disease
      recurrence, while VG did not correlate with metastasis formation. Similarly, MMP
      2 expression neither correlated with the clinical outcome of the disease nor with
      the classical histo-pathological parameters such as stage, grade, lymph node
      involvement and estrogen receptor status. Tumor cell-specific MMP-2 expression,
      however, showed a highly significant correlation with VG but not with IMD. These
      results indicate that MMP-2 expression is rather involved in the formation of
      small capillaries than in vessel maturation and tumor cell invasion. Thus, MMP-2
      expression by tumor cells may serve as indicator of strong angiogenic induction
      potential of breast tumor cells.

PMID- 12063546
TI  - Human cytomegalovirus in neoplastic cells of Epstein-Barr virus negative
      Hodgkin's disease.
AB  - Although Epstein-Barr virus (EBV) infection has been implicated in the
      development of a subset of Hodgkin's disease, the etiology of EBV-negative
      Hodgkin's disease remains to be determined. We investigated the status of human
      cytomegalovirus (hCMV) infection in 42 cases of Hodgkin's disease in a Chinese
      population. Using a nested polymerase chain reaction assay, nine of the 42 cases
      (21.4%) were found to contain EBV DNA. While only one of the nine EBV-positive
      cases demonstrated amplifiable hCMV DNA, approximately 33.3% of the EBV-negative
      cases (11/33) showed molecular evidence of hCMV infection (8 mixed cellularity; 2
      nodular sclerosis; and 1 lymphocyte depletion). All 17 lymph nodes with non
      specific reactive changes were negative for hCMV DNA. The presence of hCMV in
      Reed-Sternberg cells and their variants was further confirmed by single-cell
      polymerase chain reaction, in situ hybridization and immunohistochemical
      analysis, which demonstrated ~50% amplified hCMV DNA. These results suggest for
      the first time that hCMV infection plays a potential role in signaling the cell
      transformation and pathogenesis of Hodgkin's disease, particularly in EBV
      negative cases.

PMID- 12063547
TI  - Thiazolidinedione, a peroxisome proliferator-activated receptor-gamma ligand,
      modulates the E-cadherin/beta-catenin system in a human pancreatic cancer cell
      line, BxPC-3.
AB  - Activation of peroxisome proliferator-activated receptor (PPAR)-gamma induces
      terminal differentiation and growth inhibition associated with G1 cell cycle
      arrest in some cancer cells. The multifunctional molecule beta-catenin performs
      important roles in intercellular adhesion and signal transduction. However, no
      report has focused on actions of PPAR-gamma in regulating the E-cadherin/beta
      catenin system. We examined whether thiazolidinedione (TZD), a potent PPAR-gamma
      ligand, could modulate the E-cadherin/beta-catenin system in a human pancreatic
      cancer cell line, BxPC-3, that has been found to express PPAR-gamma. According to
      Western blotting, TZD markedly increased differentiation markers including E
      cadherin and carcinoembryonic antigen, while beta-catenin did not change
      significantly. In untreated cells, fluorescence immunostaining demonstrated beta
      catenin predominantly in the cytoplasm and/or nucleus; in TZD-treated cells, beta
      catenin localization had dramatically shifted to the plasma membrane, in
      association with increased E-cadherin at this site. Thus, a PPAR-gamma ligand
      appears to participate not only in induction of differentiation in pancreatic
      cancer cells, but also in the regulation of the E-cadherin/beta-catenin system.
      Such ligands may prove clinically useful as cytostatic anticancer agents.

PMID- 12063548
TI  - Expression of p16, p27, p53, p73 and Nup88 proteins in matched primary and
      metastatic melanoma cells.
AB  - Cutaneous melanoma is a tumor with high metastatic potential, but the mechanisms
      leading to progression are still not fully understood. In this study, we examined
      whether p16, p27, p53, p73 and Nup88 proteins were involved in the progression
      from primary to metastatic melanomas by immunocytochemistry and Western blotting
      in eleven melanoma cell lines from five matched primary and metastatic melanomas.
      We demonstrated that the primary and metastatic melanomas expressed differently
      p16, p27, p73 and Nup88 proteins. When expressed in the primary melanoma cells
      p16 and p27 were lost or reduced in almost all the metastatic melanoma cell
      lines. In contrast, p73 and Nup88 were expressed in most of the tested melanoma
      cell lines and were increased in the metastatic melanomas. p53 was expressed at
      the same level in both the primary and metastatic melanoma cells. These data
      suggest that a reduced expression of p16 and p27 and an enhanced expression of
      p73 and Nup88 might play an important role in the progression of melanoma from
      primary tumor to metastasis.

PMID- 12063549
TI  - Effect of As2O3 on cell cycle progression and cyclins D1 and B1 expression in two
      glioblastoma cell lines differing in p53 status.
AB  - Recent clinical studies have demonstrated that As2O3 is an effective drug in the
      treatment of acute promyelocytic leukemia (APL) by inducing apoptosis and
      inhibiting the proliferation of leukemia cells both in vitro and in vivo. As a
      novel anticancer agent for the treatment of solid cancer, As2O3 is promising, but
      no experimental investigations of its efficacy on glioblastoma have been
      conducted at concentrations that may be achieved clinically. In addition, the
      cell proliferation and cell cycle regulating mechanism of As2O3 has not yet to be
      clarified, especially in solid cancers. We investigated the effect of As2O3 on
      proliferation and cell cycle regulation with change in cyclins in two human
      glioblastoma cell lines differing in p53 status (U87MG-wt; T98G-mutated).
      Sensitivity to As2O3 varied depending on the dose with the IC50 of the U87MG and
      T98G cells being 1.78 and 3.55 microM, respectively. Analysis by laser scanning
      cytometry (LSC) indicated that As2O3 inhibited the proliferation of the two cell
      lines via cell cycle arrest both at the G1 and G2 phases. To address the
      mechanism of the antiproliferative effect of As2O3, we examined its effect on
      cell cycle-related proteins by means of LSC, confocal microscopy and Western blot
      analysis. As2O3 induced an increase in p53 level and a decrease in level of
      cyclin B1 combined with cell arrest at G2/M in both cell lines. Cell arrest in
      G1, however, was associated with a decline in cyclin D1 expression only in the wt
      U87MG cells. As2O3 also induced apoptosis of U87MG cells as evidenced by the
      presence of cells with fractional DNA content ( cell populations). The present
      evidence that As2O3 at relatively low concentration effectively inhibited
      proliferation of U87MG and T98G cells in vitro, suggests that the drug may be
      considered for in vivo testing on animal models and possibly clinical trials on
      glioma patients.

PMID- 12063551
TI  - GEM 231, a second-generation antisense agent complementary to protein kinase A
      RIalpha subunit, potentiates antitumor activity of irinotecan in human colon,
      pancreas, prostate and lung cancer xenografts.
AB  - GEM 231, a second-generation antisense oligonucleotide targeted against the
      RIalpha subunit of protein kinase A (PKA) was co-administered with the
      chemotherapeutic agent irinotecan, a topoisomerase-I inhibitor, to study the
      antitumor efficacy of the combination in nude mice bearing various human tumor
      xenografts. The combination treatment of GEM 231 and irinotecan produced enhanced
      and prolonged tumor-growth inhibition, compared with irinotecan monotherapy,
      against human colon (HCT-116), pancreas (Panc-1), prostate (PC3) and lung (SKMES)
      tumors in mice. The extent of tumor-growth inhibition, however, varied among the
      different tumor models studied. The tumor-growth inhibition depended on the dose
      of GEM 231 co-administered with irinotecan. The combination of GEM 231 (20 mg/kg,
      i.p., 5 days on 2 days off x 7) and irinotecan (50 mg/kg, i.v., qwk x 3) produced
      significantly longer tumor-growth delay than did irinotecan administered alone.
      Importantly, the co-administration of irinotecan and GEM 231 did not result in
      higher toxicity compared with monotherapies in the several tumor models tested.
      These results suggest that the use of irinotecan in combination with GEM 231 may
      increase the therapeutic index of irinotecan in cancer patients.

PMID- 12063550
TI  - Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent
      pathway and loss of mitochondrial membrane potential in HeLa cells.
AB  - Arsenic trioxide (As2O3) can induce clinical remission in patients with acute
      promyelocytic leukemia (APL) through induction of apoptosis. To investigate the
      potential therapeutic usage of As2O3 in cervical cancer and its possible
      mechanisms, human cervical cancer cell line HeLa was employed. The cells
      underwent apoptosis in response to As2O3, accompanied by a decrease of
      mitochondrial membrane potential and caspase-3 activation. Overexpression of Bcl
      2, however, prevented the dissipation of mitochondrial membrane potential,
      subsequently protecting the cells from As2O3-induced apoptosis. As2O3 increased
      cellular content of reactive oxygen species (ROS), especially hydrogen peroxide
      (H2O2), and the antioxidant N-acetyl-L-cysteine completely suppressed As2O3
      induced apoptosis. Furthermore, incubation of the cells with catalase resulted in
      significant suppression of As2O3-induced apoptosis. The above results indicate
      that the induction of HeLa cell apoptosis by As2O3 involved an early decrease in
      cellular mitochondrial membrane potential and increase in ROS content,
      predominantly H2O2, followed by caspase-3 activation and DNA fragmentation.

PMID- 12063552
TI  - Antisense oligonucleotide targeted to RIalpha subunit of cAMP-dependent protein
      kinase (GEM231) enhances therapeutic effectiveness of cancer chemotherapeutic
      agent irinotecan in nude mice bearing human cancer xenografts: in vivo
      synergistic activity, pharmacokinetics and host toxicity.
AB  - The RIalpha-subunit of cAMP-dependent protein kinase (PKA) is overexpressed in
      various human cancers and PKA has been suggested to be a potential target for
      cancer therapy. We have shown an antisense oligonucleotide with advanced
      chemistry (mixed-backbone oligonucleotide) targeted to PKA RIalpha-subunit
      (GEM231) to have anti-tumor activity in vitro and in vivo. In the present study,
      we demonstrated synergistic effects between the anti-PKA antisense
      oligonucleotide and the clinically used anticancer agent irinotecan, using nude
      mouse models of human cancers of colon (LS174T and DLD-1), breast (MCF-7),
      prostate (DU-145 and PC-3) and lung (H1299). To elucidate the underlying
      mechanisms, in vivo pharmacokinetics of irinotecan was determined following pre
      treatment of oligo GEM 231 in CD-1 mice and nude mice bearing LS174T xenografts.
      GEM 231 increased tissue uptake of irinotecan. However, no significant change in
      host toxicity was observed following combination treatment of irinotecan and
      GEM231 compared with irinotecan alone. These results suggest that GEM231 have a
      role in irinotecan metabolism and its antitumor activity, providing a basis for
      future development of this oligonucleotide as a chemosensitizer for irinotecan
      based therapy.

PMID- 12063553
TI  - Ribozyme mediated suppression of vascular endothelial growth factor gene
      expression enhances matrix metalloproteinase 1 expression in a human
      hepatocellular carcinoma cell line.
AB  - The levels of expression of various genes were altered in cellular transformants
      with manipulation of expression of single genes. Vascular endothelial growth
      factor A (VEGF-A) is a key molecule for tumor progression, although it is unclear
      how VEGF-A expression regulates various genes. Multiple gene expression levels
      were evaluated using cDNA arrays in a human hepatocellular carcinoma cell line
      (HLF) with suppression of the VEGF-A gene by anti-VEGF-A ribozyme (alphaVRz). The
      ribozyme-mediated suppression of VEGF-A gene solely up-regulated matrix
      metalloproteinase 1 (MMP1) gene level in HLF/alphaVRz. Levels of expression of
      other members of MMP family or tissue inhibitors of MMPs did not show any
      alteration. These results suggested that intracellular suppression of VEGF-A gene
      was specifically linked to up-regulation of MMP1 in human hepatocellular
      carcinoma cells.

PMID- 12063554
TI  - Human tumor cell infection by Newcastle Disease Virus leads to upregulation of
      HLA and cell adhesion molecules and to induction of interferons, chemokines and
      finally apoptosis.
AB  - In order to analyse immune-stimulatory effects of infection of human tumor cells
      with Newcastle Disease Virus (NDV), gamma-irradiated human breast carcinoma,
      colon-carcinoma or glioblastoma cells from defined cell lines were modified
      either by true infection with live virus or by cell surface adsorption of UV
      inactivated replication deficient virus. Modification with live but not inactive
      NDV induced in all human tumor cells IFN-beta and the chemokines RANTES and IFN
      gamma-inducible protein-10 (IP-10). In addition, infection by live NDV induced
      upregulation of HLA-ABC-molecules in all tumor lines tested and HLA-DR molecules
      in breast carcinoma lines. Two cell adhesion molecules, ICAM-I (CD54) and LFA-3
      (CD58), were also upregulated on human tumor cells after infection with live NDV.
      When infection of MCF-7 breast carcinoma cells by NDV was performed in the
      presence of neutralizing anti-IFN-beta antibodies no upregulation of HLA
      molecules was observed suggesting an important role of IFN-beta in this process.
      Forty-eight to 72 hours after infection of the irradiated tumor cells with live
      NDV, many tumor cells were dead or in early or late stages of apoptosis. These
      results provide explanations for the function of the virus-modified autologous
      tumor vaccine ATV-NDV with which promising clinical results have already been
      obtained.

PMID- 12063555
TI  - Cyclin-dependent kinase inhibitor (roscovitine) suppresses growth and induces
      apoptosis by regulating Bcl-x in head and neck squamous cell carcinoma cells.
AB  - Cyclin-dependent kinases (Cdks) play essential roles in the intracellular
      controls of the cell cycles. Roscovitine, [2-(R)-(1-ethyl-2-hydroxyethylamino)-6
      benzylamino-9-isopropylpurine], is a potent and selective inhibitor of the Cdk2
      and Cdc2. We investigated whether this compound was effective against head and
      neck squamous cell carcinoma (HNSCC) cells. Roscovitine was found to inhibit the
      growth of all 11 HNSCC cell lines in time- and dose-dependent manner and to
      diminish the Cdk2 and Cdc2 activities. An induction of apoptosis was observed in
      all cells, as judged by the cell morphology, along with the appearance of cells
      with sub-G1 DNA contents, DNA fragmentations, and poly(ADP-ribose) polymerase
      (PARP) cleavage. In four HNSCC cell lines, apoptosis was induced without
      antecedent marked cell cycle arrest, and in the other seven cell lines, cell
      cycle arrest preceded cell death. We also found up-regulation of Bcl-xS in the
      former cell lines, and in the latter cell lines, the expressions of Bcl-2 and Bcl
      xL were induced simultaneously. These results suggest that roscovitine exerts
      antitumor activities in HNSCC and is associated with induction of Bcl-xS.
      Roscovitine can be considered to provide a new chemopreventive and
      chemotherapeutic strategy for the clinical management of HNSCC.

PMID- 12063556
TI  - Effects of hyperglycemia on oxygenation, radiosensitivity and bioenergetic status
      of subcutaneous RIF-1 tumors.
AB  - Since tissue oxygen tension is a balance between delivery and consumption of
      oxygen, considerable effort has been directed at increasing the former and/or
      decreasing the latter. Techniques to decrease the rate of cellular oxygen
      consumption (increasing the distance oxygen can diffuse into tissues) include
      increasing glycolysis by administering supra-physiologic levels of glucose. We
      have examined the effect of hyperglycemia produced by intravenous glucose
      infusion on the tissue oxygenation and radiation response of subcutaneously
      implanted murine radiation induced fibrosarcomas (RIF-1). A 0.3 M glucose
      solution was delivered via tail vein injection according to a protocol that
      maintained glucose at a plasma concentration of 17+/-1 mM. The effect of this
      treatment on radiation response (clonogenic and growth delay studies), tumor
      oxygenation (needle electrode pO2 and 2-[2-nitro-1H-imidazol-1-yl]-N-(2,2,3,3,3
      pentafluoropropyl) acetamide (EF5) binding), and tumor bioenergetics and pH (31P
      NMR spectroscopy) was examined. Systemic measurements included hematocrit and
      blood glucose and lactate concentrations. The results of these studies suggest
      that these subcutaneously implanted RIF-1 tumors are both radiobiologically and
      metabolically hypoxic and that intravenous glucose infusion is not an effective
      method of modifying this metabolic state.

PMID- 12063557
TI  - Reduced response of prostate cancer cells to TRAIL is modulated by NFkappaB
      mediated inhibition of caspases and Bid activation.
AB  - We describe the effects of tumor necrosis factor alpha-related apoptosis inducing
      ligand (TRAIL) on the induction of apoptosis in two related prostate cancer cell
      lines, PC3AR and PC3Neo. TRAIL is a potent drug, which induces apoptosis
      preferentially in cancer cells. Treatment of prostate cancer cells, reduced
      survival by approximately 41% in PC3AR, but only approximately 18% PC3Neo were
      killed. Western analysis demonstrated that increased apoptotic response of PC3AR
      cells may be due to differential response of death receptors DR4, DR5 and decoy
      receptors DcR1 and DcR2. Caspases-8, -9, -3 and Bid were highly activated in
      PC3AR cells compared to PC3Neo. Furthermore, lower apoptotic response of PC3Neo
      was probably due to higher expression of NFkappaB. Blocking the function of
      NFkappaB by adenoviral infection of mutated IkappaB, increased apoptotic response
      confirming the influence of NFkappaB. Thus, we have demonstrated the role of
      NFkappaB in the differential response of prostate cancer cells to TRAIL.

PMID- 12063558
TI  - Dysfunction of the p53 tumor suppressor pathway in head and neck cancer.
AB  - It is important to examine the abnormality of the entire p53 tumor suppressor
      pathway in head and neck cancer. We examined the mRNA expressions of p53
      regulatory factors, p33ING1 and p14ARF, and a p53-target gene, p21WAF1 in head
      and neck cancer. Nine of 14 benign pleomorphic adenomas (PAs) and 7 of 8
      malignant salivary gland tumors (MSGTs) expressed p33ING1 mRNA. Thirteen of 14
      PAs expressed p14ARF mRNA, however, only 1 of 8 MSGTs expressed p14ARF mRNA.
      Eight of 14 PAs and 7 of 8 MSGTs expressed p21WAF1 mRNA. In salivary gland
      tumors, there was clear correlation between the expression of p33ING1 and p21WAF1
      (p<0.0001, r2=0.53). However, there was no correlation between the expression of
      p14ARF and p21WAF1 (p=0.6543, r2=0.009). Twenty-six of 28 oral squamous cell
      carcinomas (SCCs) expressed p33ING1 mRNA. Nineteen of 28 oral SCCs expressed
      p14ARF mRNA. All of the oral SCCs expressed p21WAF1 mRNA. In oral SCCs, the
      expressions of both p33ING1 (p=0.009, r2=0.181) and p14ARF (p=0.0009, r2=0.271)
      correlated with the expression of p21WAF1. Interestingly, 24 of 26 oral SCCs
      (92%) showed either abnormality of p53 itself or loss of expression of p53
      regulatory factors, p33ING or p14ARF. These results suggest that head and neck
      cancer often involve the dysfunction of p53 tumor suppressor pathway.

PMID- 12063559
TI  - Preventive efficacy of receptor class selective retinoids on HER-2/neu oncogene
      expressing preneoplastic human mammary epithelial cells.
AB  - Aberrant proliferation is an early-occurring event in vitro prior to
      tumorigenesis in vivo in the multistep process of carcinogenesis. Inhibition of
      aberrant proliferation therefore may represent a useful biomarker to evaluate the
      efficacy of chemopreventive agents. Retinoids have exhibited preventive efficacy
      in vitro and in vivo predominantly through the retinoic acid receptors (RARs) and
      the retinoid X receptors (RXRs). Clinically relevant biochemical and cellular
      mechanistic endpoints for chemopreventive effects of retinoids should provide
      novel biomarkers. The present study was designed to examine the preventive
      efficacy of natural retinoids, all-trans-retinoic acid (ATRA) and 9-cis-retinoic
      acid (9cisRA), and to identify the possible mechanisms for their effects using
      the HER-2/neu oncogene expressing preneoplastic human mammary epithelial 184
      B5/HER cells. Seven-day treatment with ATRA and 9cisRA exhibited a dose-dependent
      growth inhibition. Long-term (21 days) treatment with IC20 doses of 50 nM ATRA
      and 100 nM 9cisRA inhibited anchorage-dependent colony forming efficiency by
      about 75.4% (p<0.01) and 84.9% (p<0.01), respectively. Cell cycle analysis
      revealed that a 24-h treatment with IC90 doses of 2 microM ATRA and 3 microM
      9cisRA accumulates cells in the G0/G1 phase and inhibit S and/or G2/M phase of
      the cell cycle. ATRA and 9cisRA induced an 11-fold (p=0.03) and a 9-fold (p=0.04)
      increase in subG0/G1 (apoptotic) population relative to the solvent control,
      respectively. ATRA and 9cisRA induced 77% (p=0.01) and 51% (p=0.02) decrease in
      tyrosine kinase immunoreactivity, respectively. Similarly, the two retinoids
      caused almost a 50% (p=0.01) down-regulation of Bcl-2 immunoreactivity. Western
      blot analysis revealed that ATRA induced an increase in RARbeta expression and a
      decrease in RARgamma expression, while 9cisRA down-regulated RXRalpha expression.
      These data demonstrate that ATRA and 9cisRA may inhibit HER-2/neu induced
      aberrant proliferation in part by retarding cell cycle progression, down
      regulating HER-2/neu-mediated signal transduction and inducing Bcl-2-dependent
      apoptosis through a retinoid receptor-mediated mechanism.

PMID- 12063560
TI  - Dominant-negative E-cadherin alters adhesion and reverses contact inhibition of
      growth in breast carcinoma cells.
AB  - Cadherins play a crucial role in epithelial morphogenesis and mediate
      intercellular adhesion. These receptors bind catenins and are involved in signal
      transduction pathways that regulate cell growth and apoptosis, and are frequently
      down-regulated in invasive and metastatic carcinomas. In order to assess the role
      of E-cadherin in cell adhesion and growth, we transfected MCF-7 cells, a human
      breast cancer cell line, with a dominant-negative construct of E-cadherin (H-2kd
      E-cad). The dominant-negative form of E-cadherin disrupted cell-cell adhesion of
      monolayer cells and induced an epithelial-to-fibroblastic conversion without any
      significant change in integrin profiles. Whereas control cells rapidly formed
      multicellular aggregates that tightly compacted into spheroids, dominant-negative
      transfected cells failed to compact and remained as loosely-associated cells. The
      transfectants exhibited down-regulation and redistribution of endogenous E
      cadherin as well as increased levels of alpha- and beta-catenin. Importantly, the
      H-2kd-E-cad-transfected cells, when grown as multicellular aggregates, showed an
      increase in cell proliferation rate, compared to control cells. Overall, these
      observations suggest that in breast carcinoma, disruption of E-cadherin and
      catenin function modulates both cell-cell adhesion and permits escape from cell
      cell contact-involved inhibition of cell growth.

PMID- 12063561
TI  - Transformed cell-derived reactive oxygen species support and inhibit nitric oxide
      mediated apoptosis induction.
AB  - Nitric oxide has been recently shown to require interaction with extracellular
      superoxide anions and subsequent peroxynitrite formation for selective apoptosis
      induction in transformed fibroblasts. In addition to foster NO-mediated
      apoptosis, transformed target cell-derived reactive oxygen species (ROS) also
      exhibit a marked inhibitory effect directed against NO-mediated apoptosis. This
      inhibition can be abrogated by catalase and can be augmented by hydrogen peroxide
      generation through glucose oxidase. Therefore, transformed fibroblasts at high
      density seem to inhibit NO-mediated apoptosis through hydrogen peroxide
      formation. Inhibition of NO-mediated apoptosis can be explained by the
      interaction of hydrogen peroxide with NO, resulting in the generation of hydroxyl
      radicals. As hydrogen peroxide as well as NO represent far ranging species,
      hydroxyl radical generation occurs more likely distant from the cell membrane and
      therefore does not have an apoptosis-inducing effect on the cells. In total, this
      reaction is rather blunting apoptosis induction mediated by NO. The interaction
      of hydrogen peroxide with NO may have consequences for the control of transformed
      cells by NO-utilizing natural antitumor systems.

PMID- 12063562
TI  - Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast
      cancer cell lines.
AB  - Adenocarcinoma of the mammary gland is the leading type of cancer in women. Among
      these breast cancers those that are estrogen-responsive respond well to existing
      therapeutic regimens while estrogen non-responsive cancers metastasize widely,
      demonstrate a high relapse rate, and respond poorly to therapy. Over-expression
      of the arachidonic acid-metabolizing enzymes cyclooxygenase-2 and lypoxygenases
      is frequently observed in breast cancer, particularly the non-estrogen-responsive
      type, suggesting a role of the arachidonic acid (AA) cascade in the growth
      regulation of these malignancies. Adenocarcinomas of the lungs, pancreas and
      colon also frequently over-express AA-metabolizing enzymes, and recent evidence
      suggests that the growth-regulating AA-cascade in these malignancies is under
      beta-adrenergic control. Our current experiments have therefore tested the
      hypothesis that in analogy to these findings adenocarcinomas of the breast are
      also regulated by beta-adrenergic receptors via stimulation of the AA-cascade.
      Analysis of DNA synthesis by [3H]-thymidine incorporation assays in three
      estrogen-responsive and three estrogen non-responsive cell lines derived from
      human breast cancers demonstrated a significant reduction in DNA synthesis by
      beta-blockers and inhibitors of cyclooxygenase or lipoxygenases in all cell
      lines. Analysis of AA-release in one of the most responsive cell lines
      demonstrated a time-dependent increase in AA-release in response to the beta
      adrenergic agonist isoproterenol. Analysis by RT-PCR revealed expression of beta2
      adrenergic receptors in all cell lines whereas beta1-adrenergic receptors were
      not found in two of the estrogen non-responsive cell lines. Our data suggest that
      a significant subset of human breast cancers is under control of beta-adrenergic
      receptors via stimulation of the AA-cascade. These findings open up novel avenues
      for the prevention and clinical management of breast cancer, particularly the non
      estrogen-responsive types. Moreover, our findings suggest that cardiovascular
      disease and adenocarcinomas in a variety of organ systems, including the breast
      may share common risk factors and benefit from similar preventive and treatment
      strategies.

PMID- 12063564
TI  - Cell death: apoptosis versus necrosis (review).
AB  - Cell death and the subsequent post-mortem changes, called necrosis, are integral
      parts of normal development and maturation cycle. Despite the importance of this
      process, the mechanisms underlying cell death are still poorly understood. In the
      recent literature, cell death is said to occur by two alternative, opposite
      modes: apoptosis, a programmed, managed form of cell death, and necrosis, an
      unordered and accidental form of cellular dying. The incorrect consequence is the
      overlapping of: a) the process whereby cells die, cell death; and b) the changes
      that the cells and tissues undergo after the cells die. Only the latter process
      can be referred to as necrosis and represents a <no return> process in cell life.
      In this review, we discuss the excellent basic research developed in this field
      during last decades and problems that remain to be resolved in defining both
      experimentally and mechanicistically the events that lead to and characterize
      cell death.

PMID- 12063563
TI  - Rapid in vivo assay for topical oral cancer chemopreventive agents.
AB  - The cancer chemopreventive effect of topically applied phenethyl isothiocyanate
      (PEIT) was examined in a hamster buccal pouch model, in which squamous cell
      carcinomas (SCC) are induced at high frequency, by topical application of N
      methyl-N-benzylnitrosamine (MBN). The buccal pouches of eleven hamsters were
      pretreated thrice-weekly for two weeks with corn oil (CO) containing 50 mM PEIT,
      followed by 22 weeks of twice-weekly application of CO containing MBN and PEIT,
      both at 50 mM. Under similar conditions, twelve hamsters were pretreated with CO
      for 2 weeks, followed by MBN in CO. Tumor analysis was performed 19 days after
      the last application of PEIT and MBN. The incidence of tumors (approximately 90%
      SCC) in the unprotected and protected groups was 100% and 73%, respectively.
      Although total tumor incidence was marginally decreased, PEIT inhibited
      significantly the tumor frequency and tumor burden by 79% and 74%, respectively.
      In both groups, 43% of the carcinomas exhibited p53 immunohistochemical activity.
      A short-term experiment was performed to determine whether PEIT inhibits MBN
      induced cellular foci expressing gamma-glutamyltranspeptidase histochemical
      activity (gamma-GT foci). Buccal pouches of four protected hamsters received 50
      mM PEIT pretreatment on days 1 and 4, followed on days 6 and 9 by application of
      CO containing MBN and PEIT, both at 50 mM. Four unprotected hamsters were
      similarly pretreated with CO, followed by MBN in CO. gamma-GT foci were
      enumerated in buccal pouch epithelial whole mounts prepared from pairs of
      protected and unprotected hamsters on days 10 through 13. Whereas the number of
      gamma-GT foci in unprotected hamsters ranged from 98 to 356 per 10 cm2, the
      protected hamsters exhibited no more than one focus per 10 cm2. This model may be
      useful for rapid identification of chemopreventive agents, and combinations of
      agents, which inhibit initiation and promotion stages of oral carcinogenesis.

PMID- 12063565
TI  - Role of cyclinT/Cdk9 complex in basal and regulated transcription (review).
AB  - Cell division and proliferation of all eukaryotics must follow a genetic program,
      termed the cell cycle. To ensure proper progression through the cell cycle,
      proteins that are intimately involved in its regulation must be periodically
      expressed within an appropriate window of the cycle. Cyclin and cyclin-dependent
      kinases are the modular components of the core clock machinery of the cell cycle.
      Progression through the cell cycle requires the activation of Cdks. The
      activities of these classes of kinases are tightly regulated by both positive and
      negative factors, and most importantly perturbation of Cdk activities can result
      in tumorigenesis. Progress has been made recently in connecting specific cyclin
      Cdk kinase complexes and transcription. It is still unclear how cyclin/Cdk
      complexes regulate transcription, and most importantly what their substrates are.
      The aim of this review is to discuss our current understanding of the molecular
      mechanisms underlying the transcription properties of defined cyclin-dependent
      kinases, with a particular emphasis on the cyclin T/Cdk9 (P-TEFb) complex, and
      its role in the regulation of cell cycle controlling genes.

PMID- 12063566
TI  - Epithelial ovarian cancer: second and third line chemotherapy (review).
AB  - Standard therapy for patients affected with advanced epithelial ovarian cancer is
      cytoreductive surgery followed by combination chemotherapy. With this treatment,
      most patients obtain clinical complete or partial response, nevertheless, relapse
      is common and salvage chemotherapy is often needed. The probability of response
      to second line chemotherapy following platinum-based treatments is usually
      related to the platinum-free interval, even if recent studies have reported some
      other clinical features as having prognostic value, such as tumour burden and
      histology. Salvage monochemotherapy is generally used, but when the platinum-free
      interval is longer than 24 months, re-treatment with platinum compounds and/or
      taxanes is indicated. Moreover, a number of new agents with demonstrated activity
      in ovarian cancer are currently available. Sequentially used in recurrent
      disease, these agents may improve survival and/or quality of life. Among these
      new drugs, the most promising are: topotecan, doxil, gemcitabine and platinum
      analogues such as oxaliplatin, nedaplatin, satraplatin, BBR3464 and ZD0473.
      However, the real aim of salvage chemotherapy in relapsed ovarian cancer still
      remains palliative care, because complete responses are very rarely reported and
      long lasting responses are very seldom observed.

PMID- 12063567
TI  - Identification of pyrogallol as an antiproliferative compound present in extracts
      from the medicinal plant Emblica officinalis: effects on in vitro cell growth of
      human tumor cell lines.
AB  - In this study we compared the in vitro antiproliferative activity of extracts
      from medicinal plants toward human tumor cell lines, including human
      erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, erythroleukemic HEL cell
      lines. Extracts from Emblica officinalis were the most active in inhibiting in
      vitro cell proliferation, after comparison to those from Terminalia arjuna,
      Aphanamixis polystachya, Oroxylum indicum, Cuscuta reflexa, Aegle marmelos,
      Saraca asoka, Rumex maritimus, Lagerstroemia speciosa, Red Sandalwood. Emblica
      officinalis extracts have been studied previously, due to their hepatoprotective,
      antioxidant, antifungal, antimicrobial and anti-inflammatory medicinal
      activities. Gas chromatography/mass spectrometry analyses allowed to identify
      pyrogallol as the common compound present both in unfractionated and n-butanol
      fraction of Emblica officinalis extracts. Antiproliferative effects of pyrogallol
      were therefore determined on human tumor cell lines thus identifying pyrogallol
      as an active component of Emblica officinalis extracts.

PMID- 12063568
TI  - Expression of ST7R (ST7-like, ST7L) in normal tissues and cancer.
AB  - We have recently cloned and characterized ST7R (ST7-like, ST7L), WNT3, WNT3A,
      WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, WNT14B/WNT15,
      NKD1, NKD2, ARHU/WRCH1, ARHV/WRCH2, and VANGL1/STB2 using bioinformatics, cDNA
      PCR and RACE. ST7R is a paralog of tumor suppressor gene ST7 in the human genome.
      ST7R gene is clustered with WNT2B gene in human chromo-some 1p13 region, while
      ST7 gene is clustered with WNT2 gene in human chromosome 7q31 region. Multiple
      ST7R mRNAs (ST7R1-ST7R4) are transcribed due to alternative splicing. ST7R4 is
      divergent from ST7R1-ST7R3 in the C-terminal region. Here, we investigated
      expression of ST7R mRNAs in normal human tissues and human cancer. Northern blot
      analysis with S7S1 probe corresponding to ST7R1, ST7R2 and ST7R3 isoforms
      detected 4.2 kb ST7R mRNA in various normal tissues, and also large amounts of
      2.2-2.4 kb ST7R mRNAs in testis. Northern blot analysis with S7S4 probe
      corresponding to ST7R4 isoform detected 2.0 kb ST7R mRNA in testis. Expression of
      ST7R mRNAs in human cancer was next investigated using cDNA-PCR. Although ST7R
      mRNAs were almost ubiquitously expressed in 7 gastric cancer cell lines,
      expression levels of ST7R mRNAs were relatively lower in TMK1 cells. ST7R mRNAs
      were expressed in most cases of primary gastric cancer, and were up-regulated in
      2 out of 10 cases of primary gastric cancer. This is the first report on
      expression analyses on ST7R.

PMID- 12063570
TI  - Ciprofloxacin inhibits cell growth and synergises the effect of etoposide in
      hormone resistant prostate cancer cells.
AB  - Prostate cancer is the most commonly diagnosed cancer and the second leading
      cause of cancer related deaths in men in the United States. Ciprofloxacin is a
      relatively non-toxic antibiotic that can be easily administered orally with large
      volume of distribution and good tissue penetration. Studies from others and our
      laboratory have recently reported its anti-tumor activity in a variety of human
      tumor cells. In our current experiment, we studied the effect of ciprofloxacin on
      a hormone resistant prostate cancer (HRPC) cell line, PC-3. Our study shows
      significant in vitro cell growth inhibition of PC-3 cell line (p=0.0001) and also
      shows that there is a synergistic increase in the antiproliferative effect of
      etoposide when these cells are pretreated with ciprofloxacin for 24 h, prior to
      etoposide exposure (p=0.0001). Western blot analysis of the protein extracts from
      these cells showed down-regulation of Bcl-2, altering the ratio of Bax:Bcl-2
      favoring apoptosis. In our study no significant effect was seen on p21WAF1
      expression by the combination of ciprofloxacin and etoposide but there was down
      regulation of p21WAF1 gene by ciprofloxacin alone. Ciprofloxacin also inhibited
      NF-kappaB binding to DNA. Further studies in this area are warranted as the roles
      of p21WAF1, Bax/Bcl-2 and NF-kappaB may be important molecular events in
      mediating the antiproliferative and apoptosis inducing effect of etoposide in
      combination with ciprofloxacin in HRPC cells.

PMID- 12063569
TI  - Csk homologous kinase associates with RAFTK/Pyk2 in breast cancer cells and
      negatively regulates its activation and breast cancer cell migration.
AB  - Our recent observations indicated that RAFTK (also termed Pyk2 and CAK-beta)
      participated in intracellular signaling upon heregulin (HRG) stimulation and
      promoted breast carcinoma invasion. Furthermore, studies from our group indicate
      that the Csk homologous kinase (CHK), a member of the Csk family, directly
      associates with HER2/Neu and down-regulates HER2/Neu-mediated Src kinase
      activation in breast cancer cells upon heregulin stimulation. Since activation of
      RAFTK is associated with the activity of Src family kinases, we analyzed whether
      CHK is capable of opposing HRG-induced activation of RAFTK. Stimulation of human
      T47D breast cancer cells with HRG induced the tyrosine phosphorylation of RAFTK
      and its association with CHK in vitro and in vivo. This interaction was mediated
      through the Src binding site (amino acid residue at 402) of RAFTK and the SH2
      domain of CHK. RAFTK phosphorylation downstream of the activated HER2/Neu was
      greatly reduced in the presence of CHK. Maximal inhibition of RAFTK
      phosphorylation by CHK required the kinase activity of CHK. Furthermore, CHK
      inhibited the tyrosine phosphorylation of the focal adhesion-associated protein,
      paxillin, and inhibited HRG-induced T47D breast cancer cell migration. These
      findings indicate the role of CHK as a negative regulator in HRG- and RAFTK
      mediated intracellular signaling in breast cancer cells.

PMID- 12063571
TI  - CD95/CD95 ligand-independent potentiation of treosulfan cytotoxicity by BSO in
      malignant glioma cells in vitro and in vivo.
AB  - The glutathione synthase inhibitor, buthionine sulfoximine (BSO), specifically
      enhances the cytotoxic effects of treosulfan in human glioma cells. BSO depletes
      glutathione and greatly enhances treosulfan cytotoxicity in all the 12 human
      malignant glioma cell lines examined. None of these cell lines showed enhanced
      susceptibility to CD95L- or tumor necrosis factor (TNF)-alpha-induced apoptosis
      when glutathione is depleted. The combination of serial systemic BSO applications
      (300 mg/kg) and a single systemic dose of treosulfan (2.5 g/kg) reduced the
      growth of intracranially growing rat C6 gliomas in vivo by 73% whereas treosulfan
      alone reduced tumor growth by 16% and BSO alone had no effect. BSO lowered
      glutathione levels to 25-30% in peripheral blood mononuclear cells (PBMC) and to
      50% in the glioma tissue. The glutathione levels in the non-tumor-bearing
      contralateral hemisphere were unaffected by systemic BSO treatment. The main side
      effects of treosulfan, gastrointestinal and bone marrow toxicity, were not
      significantly enhanced by BSO.

PMID- 12063572
TI  - JJ1017 committee report: image examination order codes--standardized codes for
      imaging modality, region, and direction with local expansion: an extension of
      DICOM.
AB  - The digital imaging and communications in medicine (DICOM) standard includes
      parts regarding nonimage data information, such as image study ordering data and
      performed procedure data, and is used for sharing information between HIS/RIS and
      modality systems, which is essential for IHE. To bring such parts of the DICOM
      standard into force in Japan, a joint committee of JIRA and JAHIS established the
      JJ1017 management guideline, specifying, for example, which items are legally
      required in Japan, while remaining optional in the DICOM standard. In Japan, the
      contents of orders from referring physicians for radiographic examinations
      include details of the examination. Such details are not used typically by
      referring physicians requesting radiographic examinations in the United States,
      because radiologists in the United States often determine the examination
      protocol. The DICOM standard has code tables for examination type, region, and
      direction for image examination orders. However, this investigation found that it
      does not include items that are detailed sufficiently for use in Japan, because
      of the above-mentioned reason. To overcome these drawbacks, we have generated the
      JJ1017 code for these 3 codes for use based on the JJ1017 guidelines. This report
      introduces the JJ1017 code. These codes (the study type codes in particular) must
      be expandable to keep up with technical advances in equipment. Expansion has 2
      directions: width for covering more categories and depth for specifying the
      information in more detail (finer categories). The JJ1017 code takes these
      requirements into consideration and clearly distinguishes between the stem part
      as the common term and the expansion. The stem part of the JJ1017 code partially
      utilizes the DICOM codes to remain in line with the DICOM standard. This work is
      an example of how local requirements can be met by using the DICOM standard and
      extending it.

PMID- 12063573
TI  - Hand-assisted laparoscopic gastric bypass does not improve outcome and increases
      costs when compared to open gastric bypass for the surgical treatment of obesity.
AB  - BACKGROUND: Hand-assisted laparoscopic Roux-en-Y gastric bypass (Hand-Lap GB) has
      been adopted by some surgeons to treat morbid obesity because it is easier to
      perform than the total laparoscopic procedure, but to date no study has compared
      the outcomes of patients undergoing the Hand-Lap GB to those obtained with the
      open procedure (Open GB). We hypothesized that patients undergoing Hand-Lap GB
      would lose a similar amount of weight when compared to Open GB patients, while
      experiencing no increase in complications, a shorter hospital stay, and lower
      overall costs of care, in part as a result of fewer incisional hernias requiring
      subsequent surgery. METHODS: Nonrandomized, prospective data were collected on
      all patients undergoing proximal GB via Hand-Lap or open approaches between May
      1998 and July 1999. Our first 25 Hand-Lap GB procedures, performed in selected
      patients (with no extensive previous abdominal surgery) referred to two of us
      (E.J.D, M.A.S), were compared to all other (n = 62) concurrent open proximal GB
      performed by the group during this period of time in patients with body mass
      index (BMI) <50 kg/m2. RESULTS: Preoperatively, Hand-Lap GB patients did not
      differ from Open GB patients in age (40 +/- 11 vs 43 +/- 11 years), gender (92%
      female vs 81% female), incidence or type of preoperative comorbid conditions,
      preoperative weight (282 +/- 33 vs 280 +/- 37 lb), or BMI (45.5 +/- 5.4 vs 44.1
      +/- 3.3 kg/m2). (Data given as mean +/- standard deviation). Although length of
      hospital stay did not differ between groups (3.6 +/- 1.3 vs 4.2 +/- 4.6 days),
      total hospital costs were significantly higher for Hand-Lap GB ($14,725 +/- 3089
      vs. $10,281 +/- 3687, p <0.01 ANOVA). One patient in the Open GB group developed
      an anastomotic leak from the gastrojejunostomy. Follow-up revealed that Hand-Lap
      GB patients had a similar risk of postoperative complications as the Open GB
      group, including marginal ulcer (16% vs 14.5%), stomal stenosis (24% vs 23%),
      and, most notably, incisional hernia (20% vs 27%). There were no major wound
      infections or deaths in either group. One patient in each group developed a
      postoperative small bowel obstruction. Loss of excess weight in Hand-Lap GB
      patients at 12 months postoperatively was 66 +/- 14% vs 77 +/- 14% in the Open GB
      group. CONCLUSIONS: The Hand-Lap GB yielded good weight reduction in a population
      of morbidly obese patients, but at a higher cost for hospital care than Open GB.
      There was no decrease in the incidence of incisional hernias with the Hand-Lap GB
      procedure. Although Hand-Lap GB appears to be safe and effective, its failure to
      provide a decrease in hospital stay or risk of incisional hernia requiring
      subsequent surgical repair is significant. The primary role for the Hand-Lap GB
      procedure should therefore be to aid surgeons in developing skills to climb the
      steep learning curve for total laparoscopic gastric bypass, since Hand-Lap GB
      does not improve patient outcome and increases cost in comparison to the open GB
      procedure.

PMID- 12063577
TI  - The economic impact of flexible endoscopy in a large academic surgical
      department.
AB  - BACKGROUND: There has been considerable controversy concerning the value added to
      a general surgery practice when flexible gastrointestinal endoscopy is
      incorporated. The purpose of this study was to assess the economic impact of
      flexible endoscopy performed by general surgeons in a large academic practice.
      METHODS: A retrospective review of gross billing charges for a group practice of
      11 surgeons over the fiscal year 1999 was performed at the Cleveland Clinic
      Foundation. The total billing for clinic visits and outpatient and inpatient
      surgical procedures was compiled, and the percentage attributable to flexible
      endoscopy was determined. Of the 11 surgeons, three had incorporated flexible
      endoscopy into their practice. RESULTS: The three endosurgeons generated 33% of
      the total gross billing for the Department of General Surgery. Flexible endoscopy
      alone accounted for 12.2% of the total percentage of gross billings for the
      department. Meanwhile, this revenue was generated from only 8% of the workweek
      when performing flexible endoscopic procedures were performed. CONCLUSION:
      Flexible endoscopy can contribute significantly to the financial productivity of
      the general surgeon.

PMID- 12063579
TI  - Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of
      efficacy.
AB  - BACKGROUND: The advantages of treating morbidly obese patients via the
      laparoscopic approach have been demonstrated, in particular, for adjustable
      silicone gastric banding, but this operation is associated with a high rate of
      late complications. Gastric bypass and malabsorbitive procedures are feasible via
      the laparoscopic approach, but they entail a prolonged operating time and a
      consistently high morbidity rate. Laparoscopic vertical banded gastroplasty
      represents an effective alternative. METHODS: We performed 250 consecutive LVBG
      between November 1995 and February 2000. The procedure consisted of a personal
      technique designed to reproduce, by laparoscopy, MacLean's modification of the
      standard open Mason vertical-banded gastroplasty, with a calibrated transgastric
      window, a complete division between the staple lines, and a 5-cm-circumference
      polypropylene collar. RESULTS: The operative time was 95 min and the conversion
      rate was 0.8%. Operative mortality was nil; early and late complications,
      respectively, were 4.4% and 4%; the reoperation rate was 2%. Global results at 4
      years were as follows: excess weight loss (EWL) 61%, success rate (excess weight
      <50%) 76.9%, body mass index (BMI) 29.4 kg/m2. In morbidly obese patients, the
      EWL at 4 years was 62.2%, with a 77.4% success rate and a 28.4 kg/m2 BMI; in
      superobese patients, the EWL at 4 years was 54.9% with a 50% success rate and a
      35.5 kg/m2 BMI. The overall follow-up rate was 92%. CONCLUSIONS: LVBG is an
      effective and safe operation in morbidly obese patients, providing good weight
      loss with a low morbidity rate, no mortality, and minimum discomfort. However, in
      superobese patients, the weight loss results are disappointing; in these
      patients, LVBG is questionable and more complex procedures should be considered.

PMID- 12063582
TI  - [BE and lactate--old parameters in a new light].

PMID- 12063583
TI  - [Evolution of the nervous system].
AB  - This review tries to establish a synthesis between the comparative/morphological
      approach and the molecular analysis of ontogenetic processes in development and
      evolution. We use the formation of the nervous system in metazoans as a paradigm
      to point out that highly conserved molecular mechanisms may be responsible to
      generate tissues and organ systems in bilateria. We discuss the conserved role of
      the Hox genes in anterior- posterior patterning, the function of the Achaete
      scute genes and of the Notch/Delta signalling cascade in determining neural fates
      and the role of the BMP-4/Dpp-signalling pathway in positioning the neuroectoderm
      along the dorso-ventral axis of vertebrates and insects. We try to demonstrate
      that the evolution of complex body structures is based on modifying ontogenetic
      processes.

PMID- 12063584
TI  - [Neurogenic inflammation. I. Basic mechanisms, physiology and pharmacology].
AB  - Activation of sensory unmyelinated neurons by noxious stimuli evokes the release
      of neuropeptides, such as substance P and calcitonin gene-related peptide (CGRP)
      from peripheral nerve endings. These neuropeptides and subsequently released
      mediators cause a local oedema, hyperaemia and an erythema which extends beyond
      the site of stimulation (so-called flare response). Since these inflammatory
      signs depend on the function and integrity of peripheral sensory nervous systems,
      the response has been termed neurogenic inflammation. Due to the fact that nearly
      all tissues in mammals including humans are innervated by afferent sensory
      neurons, this neurogenic inflammation can occur ubiquitously throughout the body.
      Albeit first evidence showing that sensory neurons contribute to the inflammatory
      signs, described as antidromic vasodilatation, axon reflex, triple response,
      neurogenic inflammation, elicited at the level of tissue that they innervate was
      first obtained more than one hundred years ago, it was in the last two decades
      that inflammation caused by the release of neuropeptides from afferent nerve
      endings was recognised as a physiologically and pathologically relevant process.
      A large number of exogenous and endogenous substances and autacoids may stimulate
      or sensitise sensory nerve endings, thus simultaneously producing pain and
      nociceptive responses, as well as neurogenic inflammation. On the basis of recent
      research a variety of pharmacological substances and antagonists of putative
      mediators have been identified to modulate or suppress neurogenic inflammation,
      thus providing a rationale for therapeutical strategies for various diseases in
      which neurogenic inflammation is suggested to be involved. Among them, capsaicin
      and other newly developed agonists and antagonists at the vanilloid receptor have
      attracted particular attention, since they were found to be capable of
      desensitizing nociceptive nerve structures and thus of preventing development of
      neurogenic inflammation or even of abolishing an ongoing inflammatory process.

PMID- 12063585
TI  - [Variations of pain in the treatment of one classical acupuncture-point versus
      one point of Yamamoto's new scalp acupuncture].
AB  - INTRODUCTION: In an experimental design the pain reduction effect of acupuncture
      is studied and compared to the treatment of a classical acupuncture point and a
      point of the Yamamoto New Scalp Acupuncture (YNSA). METHODS: Experimental pain
      stimuli (32 per test person) were set in 42 test persons at the upper calcaneus
      edge and pain reduction was checked intra-individually by using the following
      variations of treatment: Acupuncture YNSA basis-point D, Acupuncture at the
      classical point Xiao Chang Shu = Bl 27, Acupuncture at a placebo point of the
      head, Acupuncture at a placebo point of the gluteal region. RESULTS: Evaluation
      of the data as well as a statistical investigation using a bi-factoral variance
      analysis with repeated measurements of 2 respectively 1 factor yielded following
      results: There are highly significant differences concerning pain reduction
      through the stimulation of the YNSA basis-point D and the acupuncture at the
      classical point Bl 27 (p < 0,0007). There are also highly significant differences
      concerning the verum and the placebo treatment (p < 0,00006). Further hypothesis
      of controlling the experimental design were tested. CONCLUSIONS: On the whole,
      the investigation shows that there is a marked difference between the verum and
      placebo treatment as well as a difference between the acupuncture of the YNSA
      basis-point D and the classical acupuncture point Xiao Chang Shu (Bl 27) with
      regard to pain reduction induced by experimental stimuli at the calcaneus. These
      differences are significant.

PMID- 12063587
TI  - Clinical relevance of base excess and lactate concentration.

PMID- 12063588
TI  - [Editorial].

PMID- 12063586
TI  - [Co-maintenance with propofol and midazolam: sympathoadrenergic reactions,
      hemodynamic effects, stress response, EEG and recovery].
AB  - OBJECTIVE: The study was undertaken to investigate the influence of TIVA with
      propofol, midazolam and fentanyl (comaintenance, COM-group) or TIVA with propofol
      and fentanyl (control-group) on sympathoadrenergic and hemodynamic reactions,
      stress response, EEG and recovery. METHODS: After ethical approval, 2 x 20
      patients of ASA-risk I - III over 55 years of age undergoing visceral surgery
      were investigated in a prospective randomized design. For induction of
      anesthesia, patients of the COM-group received 0,05 mg/kg BW midazolam und 1,0
      mg/kg BW propofol, and anesthesia was maintained with 0,05 mg/kg BW/h midazolam
      (until 15 - 30 min before the end of the operation) together with propofol in
      decreasing doses of 10 - 5 - 2 mg/kg BW/h. In the control-group, 2,0 mg/kg BW
      propofol were used for induction followed by decreasing doses of 10 - 5 - 2 mg/kg
      BW/h as well. Premedication (0,1 mg/kg BW midazolam orally) and weight-dependent
      doses of fentanyl (2,5 microgram/kg BW for induction, 1,25 microgram/kg BW 2 min
      before skin incision, further repetition doses of 1,25 - 2,5 microgram/kg/BW as
      required) and vecuronium were equal in both groups. Beyond consumption of
      anesthetics and recovery, sympathoadrenergic, other endocrine and hemodynamic
      reactions and SEF 90 were investigated at 7 time points before induction and
      postoperative recovery. alpha </= 0,05 was considered significant. RESULTS:
      Biometric data (mean age > 70 years) and duration of anesthesia and operation
      were comparable in both groups. Consumption of midazolam was higher in the COM
      Group (14,8 vs. 7,5 mg; p = 0,004), whereas doses of fentanyl and vecuronium were
      comparable in both collectives. Recovery was significantly (p = 0,004) delayed in
      the COM-group: observing of simple orders 12,6 vs. 5,8 min, orientation with
      respect to person 19,8 vs. 9,9 min, local orientation 23,1 vs. 11,3 min. Mean
      arterial pressure in the COM-group was throughout lower than in the control
      group, whereas heart rate was higher during the course of operation. Endocrine
      stress parameters (adrenaline, noradrenaline, antidiuretic hormone,
      adrenocorticotropic hormone, cortisol) and spectral edge frequency (SEF 90;
      Drager-pEEG) were comparable in group level and time course between both groups.
      Plasma-concentrations of midazolam were significantly higher in the COM-group.
      CONCLUSION: In elderly patients undergoing visceral surgery in TIVA and when
      compared with propofol alone, no benefit of coinduction and comaintenance with
      midazolam and propofol could be demonstrated with respect to hemodynamic
      reactions and sympathoadrenergic and other endocrine stress response as well.
      Recovery was significantly delayed after administration of midazolam.

PMID- 12063589
TI  - [Relevance of base excess and lactate concentration on diagnosis and treatment].

PMID- 12063590
TI  - [Base excess as prognostic indicator in patients with polytrauma].

PMID- 12063591
TI  - [Base excess in obstetrics].

PMID- 12063592
TI  - [Is lactate concentration always an indicator for hypoxia?].

PMID- 12063593
TI  - [Influence of lactate infusion solutions on the plasma lactate concentration].

PMID- 12063594
TI  - [Base excess and lactate concentration in infusion solutions and blood products].

PMID- 12063595
TI  - [Transarterial chemoembolization of liver metastases: Indication, technique,
      results].
AB  - We have analyzed the effectiveness of repetitive transarterial chemoembolization
      (TACE) of liver metastases as a neoadjuvant or palliative treatment modality in
      comparison with published data. Chemoembolization of liver metastases is
      performed with different cytotoxic drugs. In a 4-week interval, 357 patients were
      treated with repetitive 1,158 TACE courses performed with lipiodol, mitomycin C
      and spherex. 254 patients were treated palliatively, 18 patients symptomatically
      and 79 patients via the neoadjuvant protocol, 71 patients of whom received
      additional MR-guided laser-induced thermoablation (LITT) of the metastases after
      TACE. Our results were compared with the literature. Most of the patients with a
      low rate of local complications like vascular occlusion or liver abscess could be
      treated successfully using TACE. In 81 % of the treated lesions a primary high
      lipiodol retention was observed. In the palliative group a reduction of the tumor
      size was noted in 36 % of the lesions, a growth stop in 24 % and a reduction of
      the tumor growth rate in 40 %. In 70 % of the patients treated neodadjuvantly a
      reduction of the tumor size was found. The median survival rate of our collective
      of patients with liver metastases averages 8.6 months. In the literature median
      survival rates in patients with liver metastases were between 8.5 and 23 months
      after TACE. TACE is judged as a minimal invasive and outpatient treatment
      protocol for liver metastases. A combination of TACE and different local
      treatment modalities presents a neoadjuvant treatment strategy to control the
      diseased liver.

PMID- 12063596
TI  - [High-resolution computed tomography of the lungs in pediatric patients].
AB  - Since the introduction of the high-resolution technique more than ten years ago,
      HRCT has become an established modality for diagnosing diseases of the
      respiratory system. This is especially true for the diagnosis of lung diseases in
      adults. Experience in HRCT of the lungs is limited in pediatric patients. This
      review gives an overview of frequent and less frequent HRCT findings in pulmonary
      diseases in childhood. A purely reticular pattern is rarely observed in infants.
      Pulmonary diseases associated with overinflation are relatively frequent. Paired
      inspiratory-expiratory scans combine morphological analysis with functional
      information and have improved the diagnosis of air trapping, e. g. in post
      infectious bronchiolitis obliterans or bronchopulmonary dysplasia. Especially in
      children the high radiation exposure is a problem. Even when applying a low-dose
      protocol the radiation dose of HRCT will still exceed the dose of a chest X-ray
      by 100 times. The indication for pediatric pulmonary HRCT is limited to selected
      cases and it should be decided in agreement with the pediatric radiologists and
      the pediatric pulmonologists.

PMID- 12063597
TI  - Average glandular dose with amorphous silicon full-field digital mammography -
      Clinical results.
AB  - PURPOSE: Determination of average glandular dose with a full-field digital
      mammography system using a flat-panel X-ray detector based on amorphous silicon
      technology for a large group of patients. MATERIAL AND METHODS: The patient group
      includes women who were examined in a 4-month period with the digital
      mammographic system Senographe 2000D. The number of women was 591 and the number
      of exposures was 1116; only cranio-caudal projections were considered. Various
      quantities, including entrance surface air kerma, tube loading, and compressed
      breast thickness, were determined during actual mammography. Average glandular
      dose was determined using conversion factors g for standard breast composition.
      RESULTS: The mean average glandular dose was 1.51 mGy (0.66 - 4.05 mGy) for a
      single view. The mean compressed breast thickness was 55.7 mm. The mean age of
      patients was 55 years (34 - 81 years). CONCLUSION: The results demonstrate that
      full-field digital mammography with a flat-panel detector based on amorphous
      silicon needs about 25 % less dose in comparison with conventional screen-film
      mammography.

PMID- 12063598
TI  - Functional magnetic resonance imaging (fMRI) for fetal oxygenation during
      maternal hypoxia: initial results.
AB  - PURPOSE: To investigate the potential of fMRI to measure changes in fetal tissue
      oxygenation during acute maternal hypoxia in fetal lambs. MATERIAL AND METHODS:
      Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent
      MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver
      and myocardium was performed during acute maternal hypoxia (oxygen replaced by N
      2 O). Maternal oxygen saturation and heart rate were monitored by a pulse
      oxymeter attached to the maternal tongue. RESULTS: Changes of fetal tissue
      oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal
      intensity decreases were more distinct in liver and heart ( approximately 40 %)
      from control than in the fetal brain ( approximately 10 %). CONCLUSIONS: fMRI is
      a promising diagnostic tool to determine fetal tissue oxygenation and may open
      new opportunities in monitoring fetal well being in high risk pregnancies
      complicated by uteroplacentar insufficiency. Different signal changes in
      liver/heart and brain may reflect a centralization of the fetal blood flow.

PMID- 12063599
TI  - [Contrast-enhanced intracranial 3 D MR angiography (CE-MRA) in assessing arterial
      stenoses and aneurysms].
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic potential of CE-MR
      angiography in intracranial arterial stenoses and aneurysms. MATERIAL AND
      METHODS: Thirteen patients with intracranial arterial stenoses and ten patients
      with aneurysms, including 6 cases with GDC coil-occluded aneurysms, were examined
      by both 3 D TOF-MR angiography and CE-MR angiography. In cases of stenoocclusive
      diseases colour-coded duplex sonography and in cases of aneurysms arterial
      digital subtraction angiography served as reference method. RESULTS: Both TOF-MRA
      and CE-MRA could well depict filiform stenosis. In contrast to TOF-MRA, CE-MRA
      did not show any false positive stenosis or occlusion in regions of turbulent or
      slow blood flow. Stenoses of the medial cerebral artery could not be graded
      sufficiently by CE-MRA. In aneurysms the parent vessel was better shown by TOF
      MRA. CE-MRA, however, more sensitively detected reperfusion in GDC coil-occluded
      aneurysms. CONCLUSION: Stenoses of small vessels were graded less exactly by CE
      MRA than by TOF-MRA due to lower spatial resolution. CE-MRA, however, seems to be
      superior in regions of turbulent or slow blood flow. CE-MRA also offers
      advantages in follow-up examinations of coil-occluded aneurysms.

PMID- 12063600
TI  - [Correlation of FDG-PET and MRI/CT with histopathology in primary diagnosis,
      lymph node staging and diagnosis of recurrency of head and neck cancer].
AB  - AIM: Correct staging of head and neck cancer is important for the patient's
      prognosis and further therapeutic strategies. Aim of the present study was to
      investigate the diagnostic value of FDG-PET regarding the pre-surgical diagnosis
      of primary tumor and cervical lymph node metastases, the diagnosis of tumour
      recurrence, and the localisation of unknown primary, further to compare the
      results to those of morphological imaging modalities (CT/MRI) and to correlate
      the results of both methods with histopathological findings. PATIENTS/METHODS:
      115 patients (pts) (72 x primary diagnosis, 37 x recurrence, and 6 x unknown
      primary) underwent FDG-PET (ECAT EXACT HR+) and CT or MRI. Results were
      correlated with histopathological findings in terms of detection of primary and
      recurrent tumors as well as lymph node metastases. RESULTS: Regarding the pre
      surgical diagnosis, sensitivity and specificity for identifying primary tumors
      were 85 % and 100 % for PET and 88 % and 75 % for CT/MRI, respectively. Accuracy
      was 86 % for PET and 87 % for CT/MRI. Sensitivity and specificity for detecting
      primary lymph node involvement were 71 %/86 % for PET and 74 %/57 % for CT/MRI,
      resulting in an accuracy of 77 % with PET and 68 % with morphological imaging. In
      23 pts histopathology revealed pT1 stages with tumor diameters < 12 mm. In 8 pts
      CT/MRI and in 10 pts PET failed to identify these small primary lesions.
      Detecting tumor recurrence (n = 37) PET showed a higher sensitivity (83 %),
      specificity (76 %) and accuracy (78 %) compared to CT/MRI (sensitivity: 67 %;
      specificity: 52 %; accuracy: 57 %). In 4/6 pts with unknown primary, imaging was
      able to identify a primary lesion (3/4 in FDG-PET, 2/4 in CT/MRI), in 2/6
      patients even in the follow-up no primary tumor was found. CONCLUSIONS: FDG-PET
      provides only minor additional information to morphological imaging concerning
      diagnosis of primary tumors. At a similar level of sensitivity, however, it seems
      to be more specific regarding the lymph node involvement. PET seems to be
      superior to CT/MRI in detecting tumor recurrence as well as occult primary tumors
      in pts with known cervical lymph node metastases.

PMID- 12063601
TI  - [Visualization of coronary arteries in CT as assessed by a new 16 slice
      technology and reduced gantry rotation time: first experiences].
AB  - PURPOSE: First evaluation of image quality of a new 16-slice multidetector-row
      computed tomography (MDCT) for the assessment of coronary artery disease and
      lesion detection of the coronary arteries. MATERIALS AND METHODS: On a newly
      developed 16-slice CT scanner (SOMATOM Sensation 16, Siemens, Forchheim, Germany)
      a calcium score as well as a contrast-enhanced CT angiography (CTA) were
      performed on 4 patients with retrospective ECG-gating and a gantry rotation time
      of 420 ms to exclude or follow-up coronary heart disease. CTA was performed after
      injecting 120 ml contrast media intravenously. After medication with a ss
      Blocker, the heart rate was between 55 and 67 bpm. RESULTS: The scan time for
      calcium score was 12 s, for CTA 18 s (scan range 15 and 12 cm, respectively).
      Volume score was between 0 and 256.4. In the CT angiography the entire coronary
      tree could be visualized in all patients up to the very distal subsegmental
      branches. In two patients a complete occlusion of the RCA and the LAD were
      depicted, respectively. In one of these patients, a large aneurysm of the left
      anterior ventricular wall was also delineated. CONCLUSION: Considering our first
      experiences with the new 16-slice technology, an excellent visualization of the
      entire coronary tree including the very distal and side branches due to
      substantially increased spatial resolution seems to be achievable. In these
      patients the acquired image quality raises the hope for improved, non-invasive
      cardiac diagnostics. In larger studies, the clinical impact of this new
      technology needs to be further investigated.

PMID- 12063602
TI  - [Comparison of gradient-echo and steady state free precession sequences for 3D
      navigator MR angiography of coronary arteries].
AB  - AIM: Purpose of our study was to compare the image quality of 3D-navigator steady
      state free precession (SSFP) and gradient echo (GE) sequences for magnetic
      resonance coronary angiography (MRCA) in volunteers and patients. METHODS:
      Following informed consent 8 volunteers and 12 patients were included into this
      study. In all subjects a 3D navigator MRCA of the right and the left coronary
      artery was performed with a SSFP (TR 3.9 ms, TE 1.7 ms, FA 65 degrees, bandwidth
      540 Hz) and a GE (TR 5.8 ms, TE 2.2 ms, FA 25 degrees, bandwidth 200 Hz) sequence
      using a 1.5 T-MR-System (Magnetom Sonata, Siemens Erlangen). The slice thickness
      was 1.5 mm and the in-plane resolution was 0.9 x 0.7 mm (2) for all measurements.
      RESULTS: The blood pool showed a significantly (p < 0.01) higher signal intensity
      on SSFP images (147 +/- 36) compared to GE images (103 +/- 36). Although noise
      increased with SSFP (9.3 +/- 1.4 versus 5.3 +/- 0.9), the contrast-to-noise ratio
      between myocardium and the coronaries was significantly (p < 0.01) higher on SSFP
      images (7.8 +/- 3.7 versus 3.4 +/- 3.3). The CNR between the coronaries and the
      epicardial fat showed no significant differences (12 +/- 5 versus 13 +/- 4).
      CONCLUSION: The 3D-navigator SSFP sequence is a promising new technique for MRCA
      which improves the contrast between the coronaries and the myocardium and
      shortens the data acquisition compared to gradient-echo imaging.

PMID- 12063603
TI  - [Comparison between endorectal MRI (EMRTI) and endorectal sonography (ES) after
      surgery or therapy for rectal tumors to exclude recurrent or residual tumor].
AB  - PURPOSE: This study was designed to evaluate the accuracy and limitations for
      staging of contrast-enhanced endorectal MR imaging comparing with transrectal US
      for restaging of rectal lesions after surgery or after therapeutic radiation.
      Both methods were correlated with histologic findings. METHOD/MATERIALS: The
      efficacy of these both methods was evaluated in 30 patients with supposed
      residual or recurrent rectal neoplasms. Contrast enhanced (bolus injection of 0.1
      mmol/kg b.w. Gd-DTPA) endorectal MR imaging was performed using a 1.5 Tesla
      Magnetom. In addition endosonography (7.5 x or 10-MHz transducer) was used.
      RESULTS: In 8 patients with rectal adenoma after electro-laser resection, 8
      patients with rectal carcinoma stage pT1 after transanal resection, 8 patients
      with rectal carcinoma stage pT2 and 6 patients with rectal carcinoma stage pT3
      after regional hyperthermia with radiochemo-therapy, the following results were
      obtained during the postsurgical or posttherapeutical follow-up with respect to
      histopathological evaluation: exact staging in 86.6 % with EMRI and 63.3 % in ES,
      overstaging in 8 % (EMRI) and 23 % (ES), understaging in 0 % (EMRI) and 7 % (ES).
      The highest diagnostic accuracy was shown in EMRT in patients with rectal adenoma
      and rectal carcinoma (pT1) and after electro-laser resection or transanal
      resection during follow-up. CONCLUSIONS: Contrast enhanced endorectal MR imaging
      appears to be very promising for accurate posttherapeutical staging of rectal
      cancer and helpful in the diagnosis of recurrence or the differentiation between
      scar tissue and residual rectal tumor.

PMID- 12063604
TI  - [VIBE with parallel acquisition technique - a novel approach to dynamic contrast
      enhanced MR imaging of the liver].
AB  - PURPOSE: The VIBE (volume interpolated breath-hold examination) sequence in
      combination with parallel acquisition technique (iPAT: integrated parallel
      acquisition technique) allows dynamic contrast-enhanced MRI of the liver with
      high temporal and spatial resolution. The aim of this study was to obtain first
      clinical experience with this technique for the detection and characterization of
      focal liver lesions. MATERIALS AND METHODS: We examined 10 consecutive patients
      using a 1.5 T MR system (gradient field strength 30 mT/m) with a phased-array
      coil combination. Following sequences were acquired: T 2 -w TSE and T 1 -w FLASH,
      after administration of gadolinium, 6 VIBE sequences with iPAT
      (TR/TE/matrix/partition thickness/time of acquisition: 6.2 ms/ 3.2 ms/256 x 192/4
      mm/13 s), as well as T 1 -weighted FLASH with fat saturation. Two observers
      evaluated the different sequences concerning the number of lesions and their
      dignity. Following lesions were found: hepatocellular carcinoma (5 patients),
      hemangioma (2), metastasis (1), cyst (1), adenoma (1). RESULTS: The VIBE
      sequences were superior for the detection of lesions with arterial hyperperfusion
      with a total of 33 focal lesions. 21 lesions were found with T 2 -w TSE and 20
      with plain T 1 -weighted FLASH. Diagnostic accuracy increased with the VIBE
      sequence in comparison to the other sequences. CONCLUSION: VIBE with iPAT allows
      MR imaging of the liver with high spatial and temporal resolution providing
      dynamic contrast-enhanced information about the whole liver. This may lead to
      improved detection of liver lesions, especially hepatocellular carcinoma.

PMID- 12063605
TI  - [User friendly analysis of MR investigations of the cerebral perfusion:
      Windows(R)-based image processing].
AB  - PURPOSE: Quick and user-friendly analysis of perfusion and diffusion weighted MRI
      by means of interactive computer software. METHOD: A Windows(R)-based software
      was developed for analysis of perfusion (PWI) and diffusion (DWI) MR imaging. The
      computer program was developed in the programming language C++ using optimized
      algorithms, so that a high computing speed on Win95/98/NT systems is achieved.
      The established SVD algorithms of Ostergaard et al. for quantitative perfusion
      analysis were implemented. RESULTS: Perfusion parameter maps of the cerebral
      blood flow (rCBF), the mean transit time (MTT) and the cerebral blood volume
      (rCBV) in consideration of the arterial input function (AIF) can be calculated
      and visualized using color tables. Additionally, the calculation of "time-to
      peak" maps (TTP) and of maps of the percentage change in signal intensity (PC) is
      possible. The analysis of n = 10 normal persons shows perfusion values that agree
      with those found in the literature. DISCUSSION: With the computer program
      developed here color-coded perfusion parameter maps can be calculated easily.
      Because of the high computing speed it is possible to get information about
      tissue perfusion on the basis of the large MR data sets even in acute
      investigations.

PMID- 12063606
TI  - [Use of portable computed tomography in non-transportable patients on the
      intensive care unit: preclinical experience].
AB  - PURPOSE: To evaluate different concepts of the application of a portable CT (PCT)
      directly in a patient's ICU room versus in a specially designed interventional
      suite (IS). METHODS: 13 patients with maximum ICU treatment were examined by PCT
      and assessed with regard to their health status by ICU scores (TISS 28, MODS).
      Only patients with a therapeutic intervention scoring system 28 (TISS 28) value
      of 40 or greater were included in the study. A TISS 28 value of 40 or more
      characterizes a patient requiring maximal ICU treatment. Patients were examined
      by PCT either in the patient's room or in the IS on the ICU. Scanning time and
      personnel resource expense were determined. The multiple organ dysfunction score
      (MODS) was utilized for patient characterization. RESULTS: An average of 1.4
      hours was needed to perform a PCT scan in the interventional room. A minimum of
      4.5 hours or up to a maximum of 7.2 hours were required to perform a bedside scan
      in the patient's room. There is a noticeable difference between patients with
      respect to TISS 28. Patients examined by bedside CT were more acutely ill than
      the others by reason of MODS (8 - 18 patient-room group vs. 3 - 12 IS group).
      CONCLUSIONS: PCT performed on an ICU assures optimal treatment of patients during
      CT examination. Portable CT had more time exposure and required more personnel
      resources than examination in the IS. All PCT examinations performed directly in
      the patient's room demonstrated the diagnostic value and had direct therapeutic
      consequences.

PMID- 12063607
TI  - [System continuity and energy distribution in laser-induced thermo therapy
      (LITT)].
AB  - PURPOSE: Evaluation of the continuity and energy distribution of a laser system
      for laser-induced thermo therapy. MATERIAL AND METHODS: For evaluation of the
      continuity of laser optical devices, laser generating units and optical fibers of
      three different manufactures (Dornier, Huttinger, Somatex), we used the equipment
      to generate a laser beam of 25 Watt for 60 minutes. Measurements of the applied
      energy were done sequentially with two MY Test (Fa. Huttinger) units. We also
      performed two in vitro ablations of animal liver tissue with different fiber
      optics [Mikrodom A 13-0540, Microflexx REF A 13-0561 (Huttinger), Diffusor-Tip H
      6111-T 3, Diffusor H-6111-T 4 (Dornier), Somaflex-Diffusor (Somatex)] over 20
      minutes at- an energy flow of 25 J per second. We then evaluated the geometry of
      coagulation. RESULTS: The different equipment used for our tests showed
      differences of a maximum of 10 %. Some components did not work properly in
      certain configurations even though the manufacturer assured it would. We saw
      significant differences in the ablation characteristics of the different fiber
      optics, especially in axial and frontal directions. CONCLUSION: Knowledge of the
      different characteristics in energy distribution and ablation characteristics are
      an important factor in performing a successful laser-induced thermo therapy.

PMID- 12063608
TI  - [Cost analysis of radiological interventional procedures and reimbursement within
      a clinic].
AB  - PURPOSE: Analysis of costs for vascular radiological interventions on a per
      patient basis and comparison with reimbursement based on GOA (Gebuhrenordnung fur
      Arzte) and DKG-NT (Deutsche Krankenhausgesellschaft-Nebenkostentarif). MATERIAL
      AND METHODS: The ten procedures most frequently performed within 12 months were
      evaluated. Personnel costs were derived from precice costs per hour and estimated
      procedure time for each intervention. Costs for medical devices were included.
      Reimbursement based on GOA was calculated using the official conversion factor of
      0.114 DM for each specific relative value unit and a multiplication factor of
      1.0. The corresponding conversion factor for DKG-NT, determined by the DKG, was
      0.168 DM. RESULTS: A total of 832 interventional procedures were included. Marked
      differences between calculated costs and reimbursement rates were found.
      Regarding the ten most frequently performed procedures, there was a deficit of
      1.06 million DM according GOA data (factor 1.0) and 0.787 million DM according
      DKG-NT. The percentage of reimbursement was only 34.2 (GOA; factor 1.0) and 51.3
      (DKG-NT), respectively. CONCLUSION: Reimbursement of radiological interventional
      procedures based on GOA and DKG-NT data is of limited value for economic
      controlling purposes within a hospital.

PMID- 12063609
TI  - [Development of ultrasonography in a radiological university department from 1994
      to 2001].
AB  - BACKGROUND: In 1994, 5 % of a total of 25 718 examinations and 7 % of all 4630 B
      mode sonograms performed in the Radiology Department, University of Cologne was
      classified as not indicated. In light of these results, the health care policy
      guidelines for sonographic indications have been amended. PURPOSE: The aim of
      this study was to establish the current rate of non-indicated sonographic
      examinations performed in routine diagnostics by radiology departments at
      university hospitals, to determine the reasons for such over-diagnosis and
      identify which regulatory mechanisms can be implemented to prevent his. METHOD:
      We counted the number of 1) B-mode and 2) color-flow Doppler ultrasound imaging
      procedures carried out in patients who had had no change in symptoms within the
      previous 4 weeks or who were scheduled without reference to an existing sonogram
      (double examinations). 3) The reasons for over-diagnosis were analyzed. 4) The
      1994 survey was repeated in 2000 with an identical protocol and 5) additionally,
      a modified survey of the diagnostic questions was conducted. RESULTS: 1) Out of
      4,119 patients presenting for the first time to receive a B-mode sonogram, 443
      prior sonograms (11 %), 305 CT scans (7 %) and 57 MRI scans (1 %) were
      documented. 2) Double sonograms were carried out in 6 % of the 1,118 patients
      presenting for the first time for color-flow Doppler ultrasounds and in 16 % of
      the 651 patients assigned to receive catheter angiographies with arterial color
      flow Doppler. 2) 41 out of 55 (75 %) prior sonograms from non-university settings
      stated by 94 surgery patients were listed in the medical records. 36 out of 43
      (84 %) prior sonograms from the university hospital were repeated in the same
      patients despite the fact that the medical report with the findings was
      available. None of the 48 sonograms indicated to confirm a plausible finding
      yielded any information that was additionally relevant to therapy. 4) In the
      period April - June, 2000, 12 % of all 15,921 tests and interventions, 26 % of
      3,569 B-mode sonograms and 58 % of 1,033 abdominal sonograms performed in adults
      were classified as having not been indicated. 5) Staging and follow-up were
      stated as the most common reasons that a sonography was carried out in 46 % of
      the 1,017 adults who were given B-mode sonograms conducted from Jan - Mar, 2000
      and comprised 62 % of the 410 sonograms classified as not or probably not
      medically indicated. CONCLUSION: The results showed that a multidisciplinary
      consensus was required to establish the diagnostic value of sonographic
      procedures. Therefore, this research group drafted a hospital-internal
      interdisciplinary guideline for "abdominal transcutaneous B-mode sonography in
      oncological questions".

PMID- 12063611
TI  - [Visible to the eye...quick diagnosis in pneumology using a new rubric].

PMID- 12063612
TI  - [Birthday anniversary of the "Ruhrland Clinic"].

PMID- 12063613
TI  - [Centenary of the "Ruhrland Clinic"].

PMID- 12063614
TI  - [Indication, type of resection and results of surgery in cases of lung
      tuberculosis. A historical and regional overview].
AB  - Pulmonary tuberculosis has become a rare indication for surgical intervention in
      all industrial nations. Over a period of 10 years we overview 193 patients who
      were suffering this disease and underwent thoracotomy. Main indication (79.8 %)
      was pulmonary nodules, of unknown origin. In this cases wedge resection was
      performed. Expanded resectional techniques were necessary in cases of cavernes,
      superinfected bronchiectasis, bronchial stenosis, hemoptysis and destroyed lungs
      due to tuberculosis. Considering the heterogenous groups of patients, the
      perioperative morbidity (21.8 %) and mortality (0.5 %) has to be regarded in
      comparison to the data found in the literature.

PMID- 12063615
TI  - [Tuberculosis control in lower Franconia 1995 - 2001. Case-finding and treatment
      outcome].
AB  - BACKGROUND: How useful is active case-finding for the controlling of tuberculosis
      (TB) in Lower Franconia? What treatment outcome is being achieved and which
      factors reduce this success? METHODS: All 867 TB cases reported to the public
      health departments in Lower Franconia between 1995 and 2001 were used as
      anonymous data for a prospective study. RESULTS: Average age, gender, country of
      origin and rates of bacterial resistance of the patients coincided to a large
      degree with the data of the DZK study. The percentage of resettlers from the
      former Soviet Union with TB was, however, almost double. Therapeutic success was
      reached in approx. 79 % of the contagious TB and thus surpassed the rates of
      published investigations slightly. A negative impact upon the treatment outcome
      was caused by the following circumstances: A number of asylum seekers disappeared
      into illegality before the treatment was completed; certain TB-patients stopped
      taking the medication after surgical removal of the focus; only half of the sick
      persons who died of the disease were diagnosed when still alive. CONCLUSION:
      Active TB case-finding is useful mainly among asylum seekers and resettlers. An
      improvement of the treatment outcome in Lower Franconia is desirable but appears
      to be only possible within strict limits.

PMID- 12063616
TI  - [Pulse oximetry screening for sleep-disordered breathing in stroke].
AB  - BACKGROUND: The prevalence of sleep-disordered breathing, particularly
      obstructive sleep apnea, among stroke patients is high. Routine screening with
      the current diagnostic gold standard of polysomnography is not feasible. Pulse
      oximetry could be a simple screening test. METHODS: The signal of pulse oximetry,
      recorded during full polysomnography in 184 stroke patients during neurological
      rehabilitation, was analyzed automatically by software for desaturations >/= 4 %.
      The polysomnographic apnoea-hypopnoea-index (AHI) was used as the diagnostic gold
      standard and compared with the oxygen desaturation index (ODI). RESULTS:
      Correlation between AHI of PSG and ODI of oximetry was r = 0.84 (p < 0.001).
      Dependent on the definition of SDB (AHI 10, 15, 20 or 30/h) and the cut-off-point
      for the ODI (e. g. 15/h) sensitivity was 32 - 83 % and specificity 99 - 96 %. The
      diagnostic accuracy as determined by the area under the ROC-curve was 96 %.
      CONCLUSION: Automated analysis of pulse oximetry gives reasonable results for
      screening for SDB in stroke patients and could be used in populations with high
      pre-test probability.

PMID- 12063617
TI  - [Comparability of various measurement methods in nasal provocation with
      allergens].
AB  - Defined criteria for nasal provocation exist only for the anterior
      Rhinomanometrie (aRM). During the last years there are other techniques for nasal
      provocation in use. In this study the new instruments were compared with the
      established aRM. We examined 14 patients with perennial rhinitis. All showed
      positive skin test and RAST against D. pteronyssinus. The controls were 13 atopic
      patients sensitized against pollen but not against D. pteronyssinus and 20
      healthy volunteers. All subjects underwent nasal provocation with D.
      pteronyssinus. On the first day the provocation was unilateral. The instruments
      were the aRM, the Oscilloresistometry (ORM), the Peak Nasal Inspiratory Flowmeter
      (PNIF) and the Acoustic Rhinometry (Rhinoklack). On the second day the
      provocation was bilateral with ORM and PNIF. First we determined the limits for
      separation between a positive and negative nasal provocation test for the
      different instruments. Then we calculated the sensitivity and specificity for the
      instruments. By unilateral provocation there was a good sensitivity for all
      devices. The specificity was very good with the aRM, ORM and PNIF. In conclusion
      the PNIF is as good as the other instruments, but the Rhinoklack was less
      specific than the others.

PMID- 12063618
TI  - [Late pulmonary manifestation of ovarian and breast cancer - which contribution
      provide immunohistochemical techniques?].

PMID- 12063619
TI  - [Alveolar haemorrhage syndrome in Ceelen's disease].

PMID- 12063620
TI  - [Diagnosis and embryogenesis of partial anomalous pulmonary venous connection].
AB  - In Anomalous Pulmonary Venous Drainage one or more pulmonary veins are not
      connected with left atrium, but drain into systemic circulation or right atrium.
      The clinical signs of the shunt between pulmonary and systemic circulation
      increase during lifetime, thus the abnormality gets late or not diagnosed.
      Partial Anomalous Pulmonary Venous Drainage is a developmental disorder,
      according to embryogenesis we recommend a classification of this abnormality. Two
      case reports are given to illustrate difficulties in diagnosis of this relatively
      common abnormality. A diagnostic standard of assessment of pulmonary venous
      disorders is discussed. The "Gold Standard" of selective pulmonary Angiography in
      combination with oxygen measurement is widely used for diagnosis of Partial
      Anomalous Pulmonary Venous Drainage. In the future improvement and common use of
      modern cross sectional imaging techniques will redefine the value of conventional
      Angiography.

PMID- 12063621
TI  - [Pulmonary metabolism of nitric oxide (NO) in patients with cystic fibrosis].
AB  - Airway nitric oxide (NO) and its metabolites are involved in a number of
      physiological and pathophysiological processes. For instance, NO relaxes airway
      smooth muscle, improves airway ciliary motility, has antimicrobial effects, and
      increases expression of the CFTR (cystic fibrosis transmembrane regulator)
      protein in airway epithelial cells. Of interest, concentrations of NO and of
      bioactive S-nitrosothiols (SNOs) are decreased in the airways of patients with
      cystic fibrosis (CF). When compared to patients with relatively normal pulmonary
      NO formation, CF patients with low NO-concentrations have a significantly reduced
      pulmonary function and a higher frequency of bacterial colonisation of the
      airways with pathogens such as P. aeruginosa. As a consequence of these
      observations clinical trails have now been initiated to study possible effects of
      an augmented bronchial NO-concentration in CF-patients.

PMID- 12063622
TI  - [Diagnosis and staging of malignant pleural mesothelioma].
AB  - Malignant pleural mesothelioma (MPM) is an aggressive solid tumor with rising
      incidence and mortality. Due to a long latency period after asbestos exposure
      until tumor manifestation the peak of newly diagnosed MPM cases is to be expected
      for the year 2017 in Germany. One deciding factor for the poor prognosis with a
      median survival of 4 - 18 month is a late diagnosis at an advanced stage.
      Therefore, apart of improved stage related therapeutic options, early diagnostic
      procedures in suspected MPM play a key role. The diagnosis of MPM is made by the
      clinician as a synopsis of clinical, imaging and pathological findings. Computed
      tomography of the thorax and thoracoscopy with biopsy are the most important
      diagnostic procedures. Staging is recommended to be made as TNM description
      according to the International Mesothelioma Interest Group (IMIG) to allow a
      better comparability of various data in MPM.

PMID- 12063623
TI  - [Physical therapy in COPD--Evidence based medicine?].
AB  - Several therapeutical options of physical therapy in COPD show significant
      effects on the organism. Some of those effects are verified, but there is still
      an uncertainty about the exact influences on the disease and the beneficial
      outcome, especially because different trials describe contradictory results.
      Existing studies observed an improved respiratory mechanism with a more
      economical ventilatory work and a better gas exchange by use of physical therapy.
      Therefore the right indication for certain options of physical therapy should be
      defined, so that the outcome can be controlled and a benefit can be drawn from
      the effects. Sufficient data of existing trials for the whole physical therapy in
      COPD is still deficient. Due to an inappropriate study design and/or the number
      of observed patients a lot of clinical studies are not qualified to lead to
      significant results and recommendations. For the future it is necessary to
      investigate the exact effects of physical therapy with controlled, randomised,
      clinical trials further on. Hereby an improvement of the care of patients with
      COPD can be achieved and the beneficial effects and the outcome with physical
      therapy can better be estimated.

PMID- 12063624
TI  - [Signal detection theoretical aspects of various threshold detection procedures].
AB  - Psychoacoustic threshold detection measurements are widely used in clinical and
      research applications. A variety of procedures has been described to measure
      psychoacoustic thresholds. Each of these procedures has advantages and
      disadvantages. For clinical purposes procedures providing fast results may be
      preferred whereas for psychoacoustic research the threshold has to be determined
      as exactly as possible. Conventional procedures are based on a yes/no paradigm.
      Since these procedures are influenced by criterion shifts, n-alternative forced
      choice procedures were developed. Here the patient has to indicate the interval
      most likely to contain the signal. Additionally, it is possible to estimate the
      threshold based upon few data and comparing these to known psychometric
      functions. Following an overview outlining procedural aspects of threshold
      detection methods aspects of signal detection theory in relation to these
      procedures are discussed. Signal detection theory may help to explain why results
      obtained with various procedures may be quite different.

PMID- 12063625
TI  - [Application of Optical Coherence Tomography (OCT) in middle ear surgery].
AB  - BACKGROUND: Middle ear surgery has reached an advanced stage of development over
      the last few decades. The use of biocompatible materials offers new possibilities
      in ossiculoplasty. The exact calculation concerning the length of the implant to
      be used, however, still poses considerable difficulties and is an additional
      cause for a remaining air conduction difference or a further surgical
      intervention. METHODS: Optical coherence tomography (OCT) is a non-invasive
      imaging procedure for the imaging of tissue structures with a resolution accurate
      to micrometres. OCT can be operated touch-free and for this reason does not
      require any means of contact between applicator and sample. In the present study
      an optical coherence inferometre was coupled to an operating microscope and used
      in 5 stapedoplasties and 5 tympanoplasties type III in order to determine the
      length of the prosthesis to be used. RESULTS: The use of OCT implies an
      intraoperative measuring time of only a few seconds. The coupling in the optical
      path of an operating microscope allows trouble-free handling. The measurement of
      middle ear structures has an accuracy of 30 micrometer. The postoperative
      audiological results show a good auditory performance. CONCLUSIONS: Initial
      experience with OCT indicates that the technology will be extremely interesting
      for otosurgery. Improvements in functional pattern will enable routine
      intervention in connection with an operating microscope. Further OCT applications
      for tissue differentiation will have to follow.

PMID- 12063626
TI  - [Influence of glutathione s-transferase and cytochrome p450 polymorphisms on
      prognosis of head and neck cancer].
AB  - BACKGROUND: The polymorphic gene loci of the detoxifying enzymes GST and CYP are
      susceptibility factors for head and neck cancer. Recently, they have been
      associated with outcome in several cancers. METHODS: Accordingly, we have
      examined, in patients with squamous cell carcinoma (SCC) of the head and neck,
      associations between GSTM1, GSTT1, GSTM3, GSTP1, CYP2D6, CYP1A1 and CYP2E1
      genotypes and outcome parameters, tumor extension, histological grade, presence
      of lymph nodes, and recurrence free survival over 5 years. Genotypes were
      determined by PCR; logistic regression and a step-wise model were used to
      investigate the influence of the individual genes. RESULTS: GSTT1 0 was
      associated with T3/T4 tumor lesions in the pharynx and oral cavity (p = 0.029),
      but not laryngeal SCC cases. GSTT1 0 was also associated with histological
      differentiation (G3) in the oral cavity /pharynx, but not laryngeal SCC cases,
      although this association only approached significance (p = 0.069). CYP2D6 PM and
      HET were associated with lymph node involvement in the laryngeal SCC cases.
      CONCLUSIONS: The data demonstrate site-dependent associations between GSTT1 null
      and CYP2D6 PM and tumor extension and lymph node involvement in SCC of the head
      and neck.

PMID- 12063627
TI  - [Use of Ensemble tissue harmonic imaging to improve the resolution in ultrasound
      investigations of the head and neck area].
AB  - BACKGROUND: Using ultrasound diagnostic, deeper areas of tissue cannot be
      examined as easily as superficial areas. Therefore it was necessary to develop a
      new image processing technique for ultrasound platforms to improve the quality of
      sonographical resolution in deeper areas. Tissue Harmonic Imaging is a modern
      technique that uses the non-linear, "harmonic" parts of ultrasound waves.
      Ensemble Tissue Harmonic Imaging is a new technique that uses a "Wide Band
      Harmonic Imaging", based on a patented phase-inversion-technique, and improves
      imaging quality. AIM: Aim of the study is to show if Ensemble Harmonic Imaging
      can improve imaging quality even in superficial areas of tissue in comparison to
      fundamental B-Mode-technique. METHODS: A Sonoline Elegra(R) high-end-scanner with
      7.5 MHz linear array was used for this study. Differences of techniques
      ("fundamental"-sonographic-mode versus Ensemble Tissue Harmonic Imaging(R)-mode)
      are shown by investigation of six patients with various lesions of the head and
      neck area. CONCLUSION: In all cases there was a gain of resolution by using
      Ensemble Tissue Harmonic Imaging even in superficial areas. Ensemble Tissue
      Harmonic Imaging improves the sonographical resolution and reduces the artifacts.

PMID- 12063628
TI  - [Value of secondary coronal reconstructions in computed tomography of the
      paranasal sinuses].
AB  - INTRODUCTION: Before sinus surgery, computed tomography (CT) of the paranasal
      sinuses and anterior skull base is a standard procedure in the diagnostic
      evaluation. However, coronal sections necessary for the analysis of the complex
      anatomy of this region are often not applicable in multiple injured or elderly
      patients due to the impossibility to maintain the required position for the
      coronal scans. Secondary coronal reconstruction of primary axially acquired scans
      could help to overcome this problem. This technique was, however, hampered so far
      by an insufficient resolution in case of conventional CT. We therefore compared
      the quality of primary coronally acquired conventional CT images with the
      resolution of multiplanar reformatted coronal images of primary axially acquired
      scans by means of a new CT generation, the Multidetector Computed Tomography
      (MDCT). MATERIAL AND METHODS: 10 patients were each examined with conventional CT
      or MDCT respectively. The quality of primary coronally acquired conventional
      scans (CT) versus secondary coronal reconstructions (MDCT) was compared by
      evaluating typical anatomic landmarks. RESULTS: As compared to conventional CT,
      the coronal reconstruction of primary axially acquired scans by means of MDCT
      revealed an equal resolution and additionally no essential impairment by amalgam
      artefacts. CONCLUSION: Our results demonstrate the excellent quality of secondary
      coronal reconstructions by means of MDCT in the CT evaluation of the paranasal
      sinuses and the anterior skull base as compared to primary coronally acquired
      images via conventional CT.

PMID- 12063629
TI  - [Infantile myofibromatosis of the tongue - a case-report].
AB  - PATIENT: We report a case of infantile myofibromatosis of the tongue in a 5 month
      old female child. The parents reported discovering the tumor in the musculature
      of the tongue and the tumor had largely grown in size in the space of 4 weeks.
      The child's health was not impaired at any time. After a specimen was removed for
      a histological examination, an infantile myofibromatosis was diagnosed.
      DISCUSSION: The occurrence of these tumors in neonates and young children in the
      oral cavity and in particular in the tongue is rarely reported. Development of
      the benign tumor disease depends on the form of the tumor, which can be
      distinguished between a solitaire, a multiloculaire and a generalized form. In
      contrast to the other two forms, cases of generalized infantile myofibromatosis
      involve the visceral organs and have a poor prognosis with a mortality rate of 75
      %. Spontaneous remission is often reported in the solitaire and multiloculaire
      varieties of infantile myofibromatosis.

PMID- 12063631
TI  - [Acid burns in the oesophagus].
AB  - BACKGROUND: In the literature are different ways to treat patients with acid
      burns in the oesophagus. PATIENTS: Between 1989 and 1995, 169 patients were
      examined in the Ear, Nose and Throat Clinic at the Olga Hospital, Stuttgart, with
      suspected acid burns in the oesophagus. The patients examined included 168
      children under 13 years and one adult. If possible a rigid oesophagoscope was
      used to make the diagnosis. There were no complications. 17 patients had first
      degree acid burns, 37 second degree acid burns, 20 third degree acid burns. The
      patients with acid burns were treated with cortison and an antibioticum. Two of
      the patients with third degree acid burns developed scar strictures and these
      needed to be stretched. RESULTS: All patients were able to eat normally after the
      treatment had been completed. CONCLUSIONS: The rigid endoscopy has proved to be
      reliable for diagnosis and therapy in patients with acid burn in the oesophagus.

PMID- 12063630
TI  - [Fusafungine after tonsillectomy].
AB  - BACKGROUND: Postoperative period after tonsillectomy is characterized by
      inevitable discomfort for the patient. The aim of the study was to estimate
      whether fusafungine in spray has an effect on healing process after the
      operation, especially on pain and consumption of analgesics. PATIENTS: A
      prospective open, randomized study was performed on 68 patients (age 15 - 55)
      undergoing tonsillectomy for chronic tonsillitis. Except of standard
      postoperative therapy 34 patients received fusafungine in spray 4 times daily and
      34 patients served as a control. Pain score in the morning and in the evening,
      consumption of analgesics and visual estimation of wound healing in the tonsillar
      fossa was evaluated. RESULTS: Fusafungine in spray significantly reduces pain in
      the early days (2 - 4 day) after the operation and offers almost 16 % decrease in
      total consumption of analgesics (p < 0.04). Despite of that, total evaluation of
      pain score shows no significant differences in the both groups. The observation
      of wound healing suggests better cleanliness in 25 % of patients after
      fusafungine. CONCLUSION: Fusafungine in spray improves quality of life after the
      tonsillectomy and so completes the spectrum of adjuvant postoperative local
      treatment possibilities.

PMID- 12063632
TI  - [The monthly interesting case--case no. 53. Cogan syndrome].

PMID- 12063633
TI  - Intrinsic regional differences in androgen receptors and dihydrotestosterone
      metabolism in human preadipocytes.
AB  - Androgens play an important role in regulating the central obesity that is a
      strong risk factor for cardiovascular disease and insulin resistance. This study
      confirms that androgen receptors are present in subcultured human preadipocytes,
      with androgen receptor gene expression and saturable specific dihydrotestosterone
      binding, dissociation constant 1.02 - 2.56 nM and maximal binding capacity 30.8 -
      55.7 fmol/mg protein. There was an intrinsic regional difference in androgen
      receptor complement, with more androgen receptors in visceral than in
      subcutaneous preadipocytes. Dihydrotestosterone was metabolised by human
      preadipocytes, with more androstanediol produced by subcutaneous than visceral
      preadipocytes. While dihydrotestosterone metabolism was insufficient to explain
      the regional variation in androgen binding, both of these differences would
      reduce the androgen responsiveness of the subcutaneous preadipocytes compared
      with visceral preadipocytes. There were no gender differences in androgen binding
      or metabolism. While the direct effects of androgens on human PAs remain
      uncertain, these regional differences suggest that AR-mediated regulation of
      certain PA functions influences adipose tissue distribution.

PMID- 12063634
TI  - Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists,
      inhibits calcitonin secretion and gene expression in the human medullary thyroid
      carcinoma cell line, TT.
AB  - Somatostatin (SRIH) analogs are commonly used to treat symptoms in medullary
      thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does
      the human MTC cell line TT. The aim of this work was to evaluate whether SRIH,
      SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene
      expression in the TT cell line. CT secretion was evaluated by chemiluminescence,
      and gene expression was analyzed by Northern blot. TT cell line proliferation was
      also assessed by [(3)H] thymidine ([(3)H]thy) incorporation and viable cell
      number count. SRIH significantly (p < 0.05) reduced [(3)H]thy incorporation
      (approx. 50 %), viable cell number (approx. 20 %), CT secretion (-30 %) and CT
      gene expression (approx. 2-fold). Exposure to the SSTR2-selective agonist, BIM-23
      120, and to the SSTR5-selective agonist, BIM-23 206, did not modify CT secretion
      and mRNA levels in TT cells. Thus, SRIH inhibits DNA synthesis, cell
      proliferation, CT secretion and CT gene expression in the TT cell line, while
      SSTR2 and 5 selective agonists, although influencing DNA synthesis and cell
      proliferation, do not modify CT gene expression, suggesting that SRIH may
      influence gene expression acting through SSTRs other than subtypes 2 and 5.
      Furthermore, these findings may explain the erratic response of MTC patients in
      terms of CT plasma levels to treatment with SRIH analogs, like octreotide and
      lanreotide, which interact mainly with SSTR2 and 5.

PMID- 12063635
TI  - Increased rate of cholesterologenesis--a possible cause of hypercholesterolemia
      in experimental chronic renal failure in rats.
AB  - Hypercholesterolemia plays an important role in the lipid abnormalities in
      chronic renal failure (CRF). It is thought to contribute to both a progression of
      renal failure and atherosclerosis. Despite intensive research, the
      etiopathogenesis of hypercholesterolemia in CRF patients is still obscure. The
      present study was designed to evaluate the possible role of cholesterol
      overproduction in the development of hypercholesterolemia associated with
      experimental CRF. We found that plasma total cholesterol and cholesterol
      distributed in VLDL, LDL and HDL concentrations were significantly enhanced in
      CRF rats. Simultaneously, the rate of liver cholesterol biosynthesis in vivo
      (measured by determining the incorporation of tritium from tritiated water
      intraperitoneally injected into cholesterol ), liver microsomal 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase activity and liver HMG-CoA
      reductase mRNA presence were elevated. Significant increases in activity of liver
      malic enzyme, glucose 6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase, NADPH-producing enzyme (required for cholesterol synthesis) have
      also been observed in CRF rats. In conclusion, the increased rate of liver
      cholesterol biosynthesis due to increase of HMG-CoA reductase and NADPH-producing
      enzyme gene expression could be one of the possible causes of
      hypercholesterolemia in CRF animals.

PMID- 12063636
TI  - Estrogen regulation of uterine genes in vivo detected by complementary DNA array.
AB  - INTRODUCTION: In the present study, our aim was to identify differentially
      expressed genes involved in estrogen actions at the endometrium level in rats.
      METHODS: Thirty adult rats were ovariectomized four days prior to drug
      administration for 48 days. Rats were divided in 2 groups: I, control and II,
      conjugated equine estrogens (CCE). Total RNA was isolated from uterus, and
      differential expression was analyzed by array technology and RT-PCR. RESULTS: A
      total of 32 candidate genes were shown to be upregulated or downregulated in
      groups I or II. Among them, differential expression was already confirmed by RT
      PCR for IGFBP5, S12, c-kit, and VEGF, genes whose expression was up regulated
      during CCE therapy, and casein kinase II and serine kinase expression was the
      same level in both groups. CONCLUSION: We have demonstrated that cDNA array
      represents a powerful approach to identify key molecules in the estrogens
      therapy. A number of the candidates reported here should provide new markers that
      may contribute to the detection of target estrogen receptor. This information may
      also aid the development of new approaches to therapeutic intervention.

PMID- 12063637
TI  - Atrial natriuretic hormone, vessel dilator, long acting natriuretic hormone, and
      kaliuretic hormone decrease circulating prolactin concentrations.
AB  - The present investigation was designed to test whether four cardiac hormones-
      long acting natriuretic hormone, vessel dilator, kaliuretic hormone and atrial
      natriuretic hormone--decrease the circulating concentration of prolactin in
      humans (n = 30). Vessel dilator, kaliuretic hormone, long acting natriuretic
      hormone and atrial natriuretic hormone decreased the circulating concentration of
      prolactin to 3 %, 31 %, 27 %, and 23 % of control values, respectively, at the
      end of their infusions when infused at concentrations of 100 ng/kg body weight
      per minute for 60 minutes (p < 0.001 for each). Vessel dilator, kaliuretic
      hormone, long acting natriuretic hormone and atrial natriuretic hormone had
      sustained effects on modulating prolactin's concentrations, with circulating
      concentrations of 1 %, 64 %, 28 %, and 2 % of control values (p < 0.001) 3 hours
      after stopping their respective infusions. These results suggest that there are
      four circulating prolactin-inhibitory hormones in addition to the hypothalamic
      mediators, dopamine and corticotropin-releasing hormone, which modulate prolactin
      release. These peptide hormones' ability to decrease circulating prolactin
      concentrations may be mediated in part by dopamine and in part by their
      demonstrated ability to decrease corticotropin-releasing hormone concentrations,
      which stimulate prolactin release.

PMID- 12063638
TI  - Placental growth hormone is not suppressed by oral glucose loading in normal
      human pregnancy.
AB  - Placental growth hormone (PGH) progressively replaces pituitary growth hormone in
      the maternal circulation from mid-gestation onwards in human pregnancy. Our
      previous investigations have shown that placental growth hormone concentrations
      correlate well with foetal growth. Despite the apparent correlation between PGH
      and birthweight, the physiology of its secretion during pregnancy has not been
      well defined. We investigated the response of maternal serum PGH to oral glucose
      loading in pregnant women (n = 24) who demonstrated normal glucose tolerance at a
      mean gestation of 29 weeks. Mean (SEM) fasting PGH concentrations were high (36.9
      [6.4] ng/ml). No suppression of PGH was noted at one, two or three hours after a
      75 g oral glucose load. Similarly, no changes were noted in growth hormone
      binding protein or in calculated free PGH over the course of the glucose
      tolerance test. As expected, insulin concentrations rose sixfold and insulin like
      growth factor binding protein 1 concentrations fell by 20 % with glucose loading.
      Correlation analysis showed maternal weight, BMI, fasting serum glucose serum
      insulin to be significantly correlated with the babies' birthweight. Our results
      support the proposition that PGH concentrations in maternal serum are not
      suppressed by oral glucose loading in non-diabetic mothers.

PMID- 12063639
TI  - No direct link between albumin excretion rate and insulin resistance--a study in
      type 1 diabetes patients with mild nephropathy.
AB  - AIMS: Albuminuria is thought to be associated with insulin resistance in patients
      with type 1 and type 2 diabetes as well as in non-diabetic subjects. The aim of
      this study was to find out about any direct correlation between the albumin
      excretion rate (AER) and insulin resistance; this was investigated in patients
      with type 1 diabetes. METHODS: Euglycemic hyperinsulinemic clamps were performed
      in 18 patients with type 1 diabetes and incipient nephropathy-elevated albumin
      excretion rate (AER > 20 microg/min) but normal glomerular filtration rate (GFR)
      (81 - 135 ml/min/1.73 m (2)). RESULTS: AER, determined as mean of two overnight
      urine collections, was 137 +/- 157 (mean +/- S.D.) microg/min (range 24 - 447).
      Insulin sensitivity, expressed as the M-value, was 6.8 +/- 2.9 mg/kg/min, insulin
      sensitivity index (ISI = 100 x M/plasma insulin) 7.9 +/- 3.4 and insulin
      clearance (MCR ins ) 17.0 +/- 4.0 ml/kg/min. Simple regression analyses showed no
      direct association between AER and M, ISI or MCR ins. GFR was not associated with
      M, ISI or MCR ins in this group, either. AER was, however, positively associated
      with poor glucose control (high HbAlc) and tobacco use. CONCLUSIONS: These
      results suggest that the degree of albuminuria is not directly linked to insulin
      resistance. This was shown in type 1 diabetics, but could possibly be applicable
      in other subjects as well.

PMID- 12063640
TI  - Non-enzymatic glycation of IgG: an in vivo study.
AB  - The IgG glycation level of 30 healthy subjects and 60 type 2 diabetic patients
      with different degrees of metabolic control was evaluated by matrix-assisted
      laser desorption ionization mass spectrometry, a technique allowing the
      determination of mass increase of the IgG molecule. When applied to the digested
      mixture obtained by the action of papain on the plasma protein fraction, the same
      method established the mass increase of Fab and Fc fragments of IgG; for the
      former, a higher mass increase was found, possibly explained by its high
      reactivity to glucose. Experimental results were confirmed by molecular modeling
      calculations. Results suggest that the immunodeficiency observed in diabetic
      patients may be due to the inhibition of molecular recognition between antibody
      and antigen as a result of a change in functionality of the modified Fab fragment
      of IgG.

PMID- 12063641
TI  - Defective regulation and action of atrial natriuretic peptide in type 2 diabetes.
AB  - Increased plasma atrial natriuretic peptide (ANP) levels and impaired ANP action
      have been reported in patients with diabetes or insulin resistance. The aim of
      this study was to assess the interaction between insulin and ANP in type 2
      diabetes. In 12 normotensive, normoalbuminuric type 2 diabetics, we infused
      insulin at a high (6.6 pmol/min/kg) or, on a different day, at a low rate (0.6
      pmol/min/kg) during 4 hours of isoglycemia under isovolumic, isoosmolar
      conditions. The normal response was established in 12 healthy volunteers using an
      identical protocol. Despite higher baseline ANP levels (17.7 +/- 2.8 vs. 10.8 +/-
      1.8 pg/ml, p = 0.04), urinary sodium excretion was similar in diabetics and
      controls (113 +/- 8.5 vs. 102 +/- 8.8 mEq/24 hours, p = ns). In both groups,
      hyperinsulinemia caused a decrease in blood volume (0.33 +/- 0.10 l, p < 0.01),
      diastolic blood pressure (6 %, p < 0.02), and natriuresis. However, plasma ANP
      decreased in controls (from 12.7 +/- 1.9 to 8.6 +/- 1.4 pg/ml, p = 0.01) but not
      in type 2 diabetics (15.1 +/- 2.7 vs. 17.2 +/- 3.8 pg/ml, p = ns). We conclude
      that ANP release is resistant to volume stimulation in type 2 diabetic patients,
      and natriuresis is resistant to ANP action. This dual disruption of ANP control
      may play a role in blood pressure regulation in diabetes.

PMID- 12063642
TI  - Acute effects of valsartan on insulin sensitivity in obese, non-hypertensive
      subjects with and without type 2 diabetes.
AB  - BACKGROUND: Two studies were designed to determine whether a single dose (80 mg)
      of the angiotensin II receptor blocker (ARB), valsartan, alters insulin
      sensitivity in obese, non-hypertensive subjects with and without Type 2 diabetes.
      METHODS: Insulin sensitivity (S(I)), glucose effectiveness (S(G)), and acute
      insulin response (AIR(0-10 min)) were measured by means of a 3-hour insulin
      modified frequently sampled intravenous glucose tolerance test (FSIVGTT) before
      and after a single dose of valsartan. Study 1: obese, normotensive non-diabetic
      male subjects (n = 12), mean (SD) age 37.2 +/- 11.2 years, BMI 32.8 +/- 6.8 kg/m
      (2); Study 2: obese, normotensive Type 2 diabetic patients (n = 12), mean age
      55.7 +/- 6.9 years, BMI 35.0 +/- 6.8 kg/m (2)/l. Both studies were randomised,
      double-blind, placebo-controlled, single-dose crossover group studies involving
      subjects in two study days, two weeks apart. After fasting samples were taken, a
      300 mg/kg iv glucose bolus was injected at 0 min, and 0.05 U/kg iv insulin was
      given 20 min later. Blood samples for analysis of glucose and insulin were taken
      throughout the 3-hour study period. RESULTS: Study 1 (non-diabetic subjects) S(I)
      2.81 vs. 2.63 x 10 (-4) min (-1) per microU/ml (p = 0.54), S(G) 0.020 vs. 0.020
      min (-1) (p = 0.90), AIR(0-10) min 3305 vs. 3450 microU/min/ml (p = 0.71); Study
      2 (patients with type 2 diabetes) S(I) 0.59 vs. 0.85 x 10 (-4) min (-1) per
      microU/ml (p = 0.15), S(G) 0.013 vs. 0.014 min (-1) (p = 0.71), AIR(0-10) min 65
      vs. 119 microU/min/ml (p = 0.14), placebo vs. valsartan, respectively.
      CONCLUSION: In obese, non-hypertensive non-diabetic and Type 2 diabetic subjects
      a single dose of valsartan does not alter insulin sensitivity.

PMID- 12063643
TI  - Reorganization of thyrocyte monolayers into three-dimensional follicular
      structures correlates with major changes in urokinase production.

PMID- 12063644
TI  - [Evalutation of health monitoring in Bavaria by computer-assisted telephone
      interviews (CATI) in comparison to the German National Health Examination Survey
      conducted in 1998 by the Robert Koch Institute].
AB  - Between June 1999 and May 2000, 2051 residents of Bavaria were interviewed on
      health and health-related behaviour. The objective of the study was to assess the
      representativeness and validity of data acquired by computer-assisted telephone
      interviewing (CATI) as compared to results of the German National Health
      Examination Survey 1998. The following variables showed excellent agreement:
      subjective health status, lifetime disease prevalences, such as myocardial
      infarction, stroke, cancer, asthma, diabetes, hypertension,
      hypercholesterolaemia, utilisation of medical services, and smoking habits
      (prevalence of present and former smoking, average cigarette consumption per
      day). Minor differences were found with respect to the frequency of consulting
      naturopathic doctors. Self-reported anthropometric data from the present study
      differed considerably from the results of the objective measurements during the
      German Health Survey. We conclude that, in terms of data quality, CATI compares
      well with traditional methods such as face-to-face interviewing or mailed
      questionnaires. In view of several practical advantages of the method, we
      recommend CATI as a future basic methodology of a German health surveillance
      system consisting of different coordinated health data collections.

PMID- 12063645
TI  - [Surveillance system for assessing central nervous infections in Lower Saxony
      1998-2000].
AB  - OBJECTIVE AND METHOD: In cooperation with the district public health authorities
      in Lower Saxony a surveillance system for infections of the central nervous
      system was established from 1998 to 2000. Reporting was based on special
      questionnaires. It was the objective of this system to obtain information on the
      pathogens responsible for these infections and the corresponding age
      distribution. RESULTS: An increased risk was found for children under the age of
      15. About two-thirds of all reported central nervous infections were observed in
      this age group. The most frequent bacteria identified had been Meningococci,
      Pneumococci and Borrellia burgdorferi. They accounted for about 56 % of the
      reported bacterial infections. With respect to viral meningitis/encephalitis,
      enteroviruses were isolated in about 66 % of these cases. Twenty-five of all 628
      reported cases had a lethal outcome which was more often associated with
      bacterial than viral infections. CONCLUSIONS: Infections of the central nervous
      system still play an important role in clinical and public health medicine. For
      the future an intensive and ongoing surveillance of these infectious diseases is
      required and should exceed the regulations of the official notification system.
      To this end, a prospective register for meningitis and encephalitis cases will be
      set up in Lower Saxony in cooperation with hospitals and laboratories.

PMID- 12063646
TI  - [Psychometric analyses of occupational therapy assessment].
AB  - PURPOSE: In German-speaking countries standardised assessments measuring the
      specific aspects of occupational therapy in adults are missing. The Occupational
      Therapy Assessment (OTA) was introduced by the authors during 2000 in the context
      of a field study regarding acceptance, practicability and the influence of the
      instrument on process quality. The purpose of this study was to test the
      psychometric properties of the OTA. METHODS: : OTA was applied by 76 occupational
      therapists from 44 institutions to 833 consecutive patients. Additionally, the
      Mini Mental State Examination (MMSE) was applied. Patients completed established
      German instruments measuring functional capacity (Funktionsfragebogen Hannover -
      polyartikulare Erkrankungen; FFbH-P), body complaints (Beschwerdenliste; BL) and
      general health (Indikatoren des Reha-Status; IRES). 59 randomly selected patients
      were assessed independently by two therapists. 42 randomly selected patients were
      assesses twice for test-retest reliability. RESULTS: : For the domains
      'activities of physical self-supply', 'activities of independent living', and the
      three domains 'consequences of sensomotor/neuropsychological/psychosocial
      functioning on everyday life' internal consistency (Cronbach alpha: 0.90-0.97),
      test-retest reliability (intraclass correlation coefficient: 0.93-0.99) and
      interrater reliability (kappa: 0.72-0.82) were high. Overall, the concurrent
      validity of the domains with corresponding scales or subscales of the MMSE, FFbH
      P and IRES is satisfactory. In addition, the domains are sensitive to change.
      CONCLUSION: : The OTA is a standardised assessment measuring the specific aspects
      of occupational therapy reliably, valid, sensitive to change and sufficiently
      comprehensive.

PMID- 12063647
TI  - [Career wishes and career worries of medical students--results of focus group
      interviews].
AB  - PURPOSE: In addition to a prospective longitudinal study of career determinants
      in young physicians the aim of the present qualitative study was to gather
      information on 1. experiences by medical students during their clinical year, 2.
      their understanding of career, 3. their career desires and worries regarding the
      compatibility of profession and family, and 4. their wishes of career promotion.
      METHOD: Twenty-two subjects from the initial sample of 377 students from the
      three medical schools in the German-speaking part of Switzerland in their senior
      year agreed to participate in focus groups. The interviews were structured by an
      interview guideline, the material was tape-recorded, transcribed, paraphrased,
      and categorised. RESULTS: 1. The experiences during the clinical year mainly
      brought a gain of practical skills. Female students were disillusioned by the
      daily routine at the hospital. 2. Career was associated with a poor quality of
      life. 3. Regarding career wishes male students showed more optimistic attitudes,
      while female students suppressed their career wishes in prospect of a spouse
      and/or family. Female and male students had rather traditional ideas about the
      compatibility of their profession and family. The only acceptable models were the
      so-called life cycle model (professional work - family phase - return to work for
      women) or a reduced professional engagement of the woman during the family phase.
      4. The majority of the participants wanted some sort of career promotion, female
      students at the beginning, males rather in a later stage of their career.
      CONCLUSION: The results of the longitudinal study will show whether the
      assessments of the subjects in the focus groups will be confirmed during their
      further career.

PMID- 12063648
TI  - [Risks, chances and perspectives of restricting the free choice of doctors by
      patients].
AB  - Population surveys regarding free access to primary care physicians and medical
      specialists focus on selected aspects of public opinion. They are helpful but not
      sufficient in answering the relevant question: 'What are appropriate and
      efficient ways of access to the health care system?'. More important than survey
      results would be options for practical decisions by the patients themselves,
      based on a system offering different possibilities of choice. Competent piloting
      by 'gatekeepers' would need a problem- oriented and patient-centred medical
      education for primary-care physicians, starting during medical education and
      training and continuing throughout the professional medical careers. It should
      focus on three additional issues: New, alternative and unbiased ways of access to
      medical care should be developed, tried and evaluated to ensure beneficial use of
      the full potential of our health care system.

PMID- 12063649
TI  - [The opinion of general practitioners in East and west Germany on
      rehabilitation].
AB  - GPs in the former German Democratic Republic (now called 'New Federal States')
      and in West-Germany (the 'Old Federal States') differ more than ten years after
      reunification in several respects. This survey shows that they have different
      attitudes to medical rehabilitation programmes as well. Written questionnaires
      were sent to all GPs in Hamburg and Schleswig-Holstein (representing the Old
      Federal States) and in Sachsen-Anhalt and Mecklenburg-Vorpommern (representing
      the New Federal States). GPs in the New Federal States value medical
      rehabilitation in general and single programmes more than those in the old ones.
      They see a higher number of patients who have a good benefit from rehabilitation
      and estimate the degree of overuse as smaller. They observe more often patients
      who do not take part in a rehabilitative programme because they are afraid of
      losing their job. The higher proportion of female GPs in the New Federal States
      does not explain these differences.

PMID- 12063650
TI  - [Health situation of homeless in a health care home in Hannover].
AB  - BACKGROUND AND AIM: Extension of the medical health care system for social fringe
      groups by means of a special 'Health Care Apartment' for homeless people with an
      ambulatory nursing service. Between 55-70 % of the homeless people in Germany are
      in-patients for medical treatment nearly once a year. Only 10-20 % have a family
      doctor. METHOD: : The pilot experiment of a special Health Care Apartment for
      homeless people was scientifically evaluated for approximately one and a half
      year under socio-medical and socio-economic viewpoints. Every patient passes a
      standardized interview at admission and discharged with one validated systematic
      setup and one specifically developed questionnaire. RESULTS: : The mean age of
      the 36 investigated persons was 48.7. 36.1 % (13) of the patients lived in
      divorce. About 86.1 % (31) of the patients had secondary school qualifications,
      69.4 % (25) had learnt a profession. All were unemployed. Two-thirds of them
      stated they had been found guilty of a criminal offence within the last few
      years. 44.5 % (16) had been homeless for 3 or more years. Approximately x of the
      homeless were addicted to alcohol, according to the employees entrusted with
      looking after the inmates. The main reasons for the average 8-week stay in the
      medical department were diseases of the skin and skeletal system, which had
      caused several hospital admissions in the past. The satisfaction of their own
      health status improved by 66 % from the day of their admission to the day of
      their discharge. 72.2 % (26) said they could get easier medical support in the
      Health Care Apartment. Supported by intensive socio-pedagogical care, 55.5 % (20)
      of the homeless people could be discharged from the special Health Care Apartment
      to other arrangements for homeless people, respectively to own apartments.
      CONCLUSION: : The pilot study of the special Health Care Apartment for homeless
      people in Hannover closes a gap in the provision of medical care which exists in
      many major cities. Moreover, hospital admissions for homeless people can be
      prevented and their social reintegration promoted.

PMID- 12063651
TI  - [Prevention--a task for all elements of society].

PMID- 12063652
TI  - Outcomes research in facial plastic surgery.

PMID- 12063653
TI  - Outcomes research and facial plastic surgery.
AB  - Outcomes research examines the delivery of medical care from the patient's
      perspective, using unique instruments and methodologies. Outcome studies can
      measure the effectiveness of treatments or interventions in individual patients
      or in large populations, using prospective observational research designs. The
      steps in performing outcomes research are as follows: identify and define the
      disease or procedure of interest, create a staging system for disease severity,
      identify important co-morbid conditions, choose or design an outcomes instrument
      to measure treatment outcomes, and design a study to assess outcomes
      prospectively. Although there is currently a dearth of outcomes instruments
      available for use in facial plastic and reconstructive surgery, some new
      instruments are being developed, and even using existing tools outcomes research
      should prove to be a valuable research tool for facial plastic surgeons to
      demonstrate improved quality of life and functional status in their patients.

PMID- 12063654
TI  - Outcomes instruments in facial plastic surgery.
AB  - The accurate measurement of patient-related outcomes of facial plastic surgery
      procedures relies upon the development, standardization, and use of validated,
      procedure-specific quality of life instruments. Although other fields of medicine
      and surgery have embraced the use of such instruments for the quantification and
      measurement of otherwise subjective or qualitative aspects of patient
      satisfaction, in the fields of both general and facial plastic surgery, little
      has been done in this realm. The study of outcomes research and the application
      of outcomes research to facial plastic surgery have already been discussed in
      this issue. Outcomes research is founded upon the ability to measure in some
      fashion those aspects of patient satisfaction that have hitherto been ignored or
      at best poorly quantified in the assessment of the results of a medical or
      surgical intervention. In facial plastic surgery, particularly cosmetic facial
      plastic surgery, the overwhelming majority of results are subjective in nature,
      be they patient related or based upon the surgeon's own personal assessment of
      outcome. For this reason, the use of validated instruments to quantify and
      measure these results is of particular importance in facial plastic surgery
      compared with other fields of medicine where many outcomes are objectively
      determined, such as mortality. This article outlines the background of the use of
      quality of life instruments in the field of outcomes research to provide a basic
      understanding for the application of such tools to the work of facial plastic
      surgery. Specific instruments that have already been developed and validated are
      described as well. Finally, future directions are highlighted that may allow the
      improved measurement of patient satisfaction as the field of outcomes research in
      facial plastic surgery continues to evolve.

PMID- 12063655
TI  - Statistical inference in facial plastic surgery: perspectives and alternatives.
AB  - Facial plastic surgeons often must make decisions with imperfect information.
      Statistical inference is fundamentally the practice of using data to draw
      conclusions about uncertain phenomena. It is important, therefore, that facial
      plastic surgeons engaged both in clinical practice and in research have an
      understanding of statistical concepts to conduct research with results that are
      meaningful, to assess the validity of published research, and to adopt the most
      effective techniques and treatments. The purpose of this article is to provide an
      overview of classical statistical methods that are encountered frequently in
      facial plastic surgery research, discuss issues of interpretation of results, and
      introduce an alternative paradigm for conducting statistical inference.

PMID- 12063656
TI  - Introduction to cost analysis in facial plastic surgery.
AB  - Resource allocation in health care is increasingly guided by financial
      considerations. The cost of care influences treatment decisions not only for
      health care organizations but also for patients, especially in the fee-for
      service marketplace that typifies cosmetic surgery. The purposes of this article
      are to improve the facial plastic surgeon's understanding of cost analyses and to
      facilitate critical reading of the literature. We describe basic concepts in
      economic analyses, such as perspective of analysis, the difference between costs
      and charges, and the importance of discounting. We also introduce the importance
      of assessing treatment effectiveness and quality of care. In a review of existing
      cost-based studies in facial plastic surgery, we found a paucity of rigorous
      treatment analyses. There are numerous opportunities to pursue economic analysis
      in facial plastic surgery. We discuss potentially rewarding directions for future
      research.

PMID- 12063657
TI  - Outcomes with eye reanimation microsurgery.
AB  - This study reviews the various microsurgical techniques available to reanimate
      the paralyzed eye sphincter. Traditional as well as several innovative procedures
      are described that the senior author has used over the past 20 years. The methods
      of evaluating such outcomes are discussed and analyzed with regard to eye
      reanimation. An independent panel of reviewers evaluated standardized
      preoperative and postoperative videos documenting eye closure and blink in
      patients with lagophthalmos. A significant difference in overall postoperative
      outcome of both eye closure and blink was demonstrated. In this particular
      population, those patients who underwent dynamic procedures more often yielded
      better results than those who did not. Detailed video documentation and
      independent grading of outcomes of eye closure and blink are necessary to assist
      in developing effective surgical treatments for paralytic lagophthalmos. Accurate
      measurement of the results of these interventions remains a considerable
      challenge in the field of eye reanimation microsurgery.

PMID- 12063659
TI  - Outcomes of facial cosmetic procedures.
AB  - Facial cosmetic procedures lend themselves to outcomes studies in ways that
      traditional reconstructive procedures may not. The most important measures of
      outcome in facial cosmetic surgery are quality of life and patient satisfaction,
      in contrast to other, more objective measures such as complications or mortality
      rates. For this reason, outcomes research in facial cosmetic surgery deserves a
      special focus of attention. In this article, we review outcomes studies for the
      more common facial cosmetic procedures, discuss in depth what aspects of patient
      related satisfaction have been quantified by these existing studies, and
      highlight the direction that future outcomes research projects may wish to
      follow. There exists an abundance of potential interesting areas of study in
      facial cosmetic surgery, and the application of outcomes research methodology to
      these realms may allow the facial plastic surgeon to better define the success or
      failure of each individual facial cosmetic surgery procedure.

PMID- 12063658
TI  - Outcomes research in head and neck reconstruction.
AB  - Modern management of advanced upper aerodigestive tract malignancy often results
      in profound effects on function and appearance. These functions include speech,
      deglutition, mastication, taste, oral hygiene, and airway maintenance. The most
      commonly studied site in the head and neck is the oromandibular complex. The
      primary goals of reconstruction are the preservation and restoration of these
      functions along with socially acceptable cosmesis. Achieving these objectives is
      not to be accomplished at the expense of acceptable oncologic principles. With
      the availability of microvascular free tissue techniques, single-stage
      oromandibular reconstruction is now commonly performed. Few studies, however,
      have critically examined the functional outcomes of these techniques. To date,
      these investigations have been limited and retrospective. Lack of a uniform
      system for reporting defect size and locations as well as patient function and
      quality of life has limited the utility of the available data. In this article,
      outcomes research in head and neck reconstruction is discussed with regard to
      objective study parameters using the oral cavity as a model. Pertinent current
      literature is cited.

PMID- 12063660
TI  - Psychological issues in patient outcomes.
AB  - This article provides an overview of the psychological issues of facial plastic
      surgery patients. It begins with a review of the research on the preoperative
      psychological characteristics of cosmetic surgery patients. Results from the
      studies assessing postoperative changes in psychological status are reviewed. The
      psychological issues of specific patient groups, including adolescents and male
      patients, are discussed. Individuals who undergo plastic surgical procedures as a
      result of craniofacial anomalies or facial injuries often face a myriad of
      psychosocial challenges. These issues are outlined in brief. The article
      concludes with a discussion of two psychiatric conditions, body dysmorphic
      disorder and posttraumatic stress disorder, that may be frequently encountered by
      facial plastic surgeons.

PMID- 12063661
TI  - Claims prevention for the aesthetic surgeon: preparing for the less-than-perfect
      outcome.
AB  - Many surgeons will find themselves faced with a claim of malpractice. At times
      this may be due to a less-than-perfect outcome. Well over half of such claims are
      preventable, as most are based on failures of communication and/or patient
      selection criteria. Attention to legal principles such as standard of care,
      warranty and disclosure, knowledge of patient factors, and the ability to
      communicate clearly and effectively will hopefully maximize the possibility of
      remaining a claims-free surgeon.

PMID- 12063662
TI  - [Medical dissertation: differences between successful and aborted research
      projects].
AB  - BACKGROUND AND OBJECTIVE: To obtain the title "Doctor medicinae" in Germany a
      dissertation is required. There are no data currently available to compare
      successful and unsuccessful student research projects. This study's aim was to
      determine observational differences between the two groups of successful and
      unsuccessful dissertations pursued by medical students. METHODS: All medical
      students of the 11 (th) to 14 (th) terms of study at the Charite Hospital in
      Berlin (n = 1036; 560 females [54.1 %] and 476 males [45.9 %]) received a
      questionnaire, which invited them to describe the current and/or up to two
      aborted dissertations. The returned questionnaires were classified into
      "successful" and "unsuccessful" dissertations. RESULTS: 324 (31 %) students
      responded, describing 348 dissertation projects at the Charite. Of these, 72 were
      identified as successful and 65 as unsuccessful. Successful dissertations were
      significantly better supervised (the supervisor was available more often [64 %
      vs. 29 %]; the supervisor was more often helpful [57 % vs. 9 %]). Further,
      planning of successful projects was significantly better (dissertation faithful
      to agreed-on specifications [42 % vs. 5 %]; financially supported [39 % vs. 8
      %]). In addition, efforts to attract the student as a future research partner
      were significantly more frequent when the dissertation was successful (50 % vs.
      17 %). CONCLUSION: Successful dissertations are clearly the result of better
      preparation and continuous close supervision. To improve the chances of success,
      better planning and supervision are essential. Moreover, financial support and
      proper preparation for scientific work, e. g., by special courses, maybe
      promising instruments to increase the fraction of successful dissertations.

PMID- 12063663
TI  - [Aneurysm of the popliteal vein causing pulmonary thromboembolism that required
      resuscitation].
AB  - HISTORY AND ADMISSION FINDINGS: A previously healthy 40-year-old varnisher was
      admitted because of increasing dyspnoea. His clinical status rapidly
      deteriorated. He was referred to a cardiology intensive care unit but had to be
      resuscitated during transport. His condition became stable under controlled
      ventilation and analgesics. There were no other contributory abnormal findings.
      INVESTIGATIONS: The concentration of D-dimers was raised. Pulmonary angiography
      demonstrated multiple bilateral occlusions of the segmental arteries. TREATMENT
      AND COURSE: Extubation became possible after thrombolysis with recombinant tissue
      plasminogen activator (rTPA). There was no evidence of leg or pelvic vein
      thrombosis. But a hard mass was palpated in the left popliteal fossa and
      extensively thrombosed saccular aneurysm of the popliteal vein was found. The
      aneurysm was resected and a venous graft was interposed. There were no further
      thromboemboli under oral anticoagulation. Two years later the venous graft was
      occluded with adequate collateral circulation. CONCLUSION: Aneurysm of the
      popliteal vein is a rare vascular anomaly of unknown pathogenesis. In patients
      with repetitive episodes of lung embolism peripheral aneurysms must be taken into
      consideration.

PMID- 12063664
TI  - [Diabetic nephropathy - Case report].

PMID- 12063665
TI  - [Diabetic nephropathy - Diagnostic].

PMID- 12063666
TI  - [Diabetic nephropathy - Treatment].

PMID- 12063667
TI  - [Diabetic nephropathy--quiz for certification].

PMID- 12063668
TI  - [Diabetic nephropathy--evaluation questionnaire].

PMID- 12063669
TI  - [Quality management in hospital hygiene].

PMID- 12063670
TI  - [Advertising of physicians by newspaper ads. Decision of the Federal Regulation
      Court on 18 February 2002].

PMID- 12063671
TI  - [Why should carotid artery restoration be carried out in acute occlusion of the
      internal carotid artery].

PMID- 12063672
TI  - [DRGs--sword of Damocles or silver strip?].

PMID- 12063673
TI  - Tumor markers as clinical cancer tests--are we there yet?

PMID- 12063674
TI  - Issues and barriers to development of clinically useful tumor markers: a
      development pathway proposal.
AB  - There are few tumor markers that are clinically useful in predicting therapeutic
      responses or patient outcomes despite nearly 20 years of advances in molecular
      biology. We discuss a variety of issues and barriers that have affected movement
      of clinical tests from research into clinical practice. Studies of new markers
      frequently lack clear hypotheses and are generally underpowered to reach
      statistically valid conclusions. Relevant clinical endpoints may not be possible
      to evaluate, often leading to suboptimal study designs. Major stumbling blocks
      exist because studies are rarely comparable. This makes it difficult to determine
      why results vary from study to study. It also prevents pooling of small datasets
      for analysis. We propose a tumor marker development pathway that we think will be
      more efficient and effective. The pathway depends on developing statistically
      valid study designs, focusing on assay refinement and standardization early in
      the process, including assay details in publications, and providing data in a
      format that allows comparison with other studies. The process described should be
      applicable to development of new technologies that include analysis and
      interpretation of large, complex datasets. The proposed marker development
      pathway will require thoughtful refinement and expansion, but it should begin a
      productive dialog.

PMID- 12063675
TI  - Issues in clinical trial design for tumor marker studies.
AB  - Scientific inquiry into the discovery, development, and application of tumor
      markers is proceeding rapidly. Despite this explosion in research and interest,
      the design of studies to formally assess the value of tumor markers in clinical
      practice is inconsistent and immature. Indeed, few markers have been widely
      accepted into standard clinical practice. Many issues must be prospectively
      considered in a methodical, systematic, and scientific fashion if progress is to
      be made in the development of validated tests that will have value in the
      management of patients with cancer. The purpose of this report is to present a
      discussion of the issues involved in designing clinical studies of putative tumor
      markers which provide sufficient data to result in the incorporation of the
      marker into clinical practice. We will focus on the design of studies to
      demonstrate and validate the clinical utility of both prognostic and predictive
      markers. Topics to be covered include issues of patient and sample heterogeneity,
      the prevalence of the marker, the sample capture rate, and the choice of
      endpoints. This will be followed by explicit consideration of study design,
      specifically the trial randomization schema for both prognostic and predictive
      factor studies.

PMID- 12063676
TI  - c-erbB-2 in breast cancer: development of a clinically useful marker.
AB  - c-erbB-2 amplification and/or overexpression occurs in 20% to 30% of breast
      cancers and appear to be associated with a more aggressive phenotype. Detecting
      abnormalities in c-erbB-2 might provide important clinical information for breast
      cancer patients. However, several of the potential clinical uses of c-erbB-2
      remain unproven. Many variables influence c-erbB-2 results, including selection
      and characteristics of test populations and methods of analysis. Current
      literature suggests two roles for c-erbB-2, either as a pure prognostic factor
      with no association with therapy or as a factor predictive of benefit from
      specific types of systemic treatments. c-erbB-2 appears to be only a weak
      prognostic factor, although some individual studies suggest greater prognostic
      importance. c-erbB-2 abnormalities appear to predict for relative, but not
      absolute, resistance to endocrine therapy in estrogen receptor (ER)-positive
      women. When adjuvant chemotherapy is indicated, some studies have indicated that
      patients with c-erbB-2-positive cancers (by immunohistochemistry [IHC] or
      fluoresence in situ hybridization [FISH]) receive more benefit from anthracycline
      containing regimens as compared to alkylating agents. c-erbB-2 testing appears
      critical for selecting patients with metastatic disease who should receive the
      anti-c-erbB-2 antibody, trastuzumab. Prospective randomized clinical trials of
      trastuzumab as adjuvant therapy are underway. Well-designed, prospective,
      randomized clinical trials (designed to test the value of c-erbB-2) or formal
      meta-analyses will help to better establish the predictive role of c-erbB-2 in
      breast cancer.

PMID- 12063678
TI  - Clinical translation of gene expression profiling in lymphomas and leukemias.
AB  - Current lymphoma classification schemes that incorporate information on
      immunophenotype and genetic aberrations of the neoplastic cells represent a first
      attempt at a molecular diagnosis of these malignancies. Gene expression profiling
      using DNA microarrays promises to dramatically enhance molecular diagnosis by
      quantitating gene expression in tumor cells on a genomic scale. In this review,
      we focus on recent studies of diffuse large B-cell lymphoma (DLBCL) and chronic
      lymphocytic leukemia (CLL) that illustrate the effectiveness of gene expression
      profiling in defining molecularly distinct diseases. In DLBCL, germinal center B
      like (GCB) and activated B-cell-like (ABC) subgroups differ in the expression of
      more than 1,000 genes and have a markedly different clinical outcome, suggesting
      that this diagnostic category includes at least two distinct molecular diseases.
      In CLL, by contrast, all cases express a characteristic set of genes, suggesting
      that CLL should be considered a single disease. Nonetheless, two subtypes of CLL
      exist that are distinguished by the presence or absence of immunoglobulin gene
      mutations, by the expression of approximately 175 genes, and by clinical course.
      Clinical translation of these results should be implemented initially in clinical
      trials where gene expression profiles could identify subsets of patients that are
      particularly responsive to the therapies being evaluated. As the armamentarium of
      molecularly targeted therapies expands, molecular diagnosis will be seen as an
      integral component of clinical management.

PMID- 12063677
TI  - P53 gene mutations: case study of a clinical marker for solid tumors.
AB  - P53 is a tumor-suppressor gene that codes for a multifunctional DNA-binding
      protein involved in cell cycle arrest, DNA repair, differentiation, and
      apoptosis. The P53 gene is mutated in approximately 50% of human cancers and in
      germline DNA of families with inherited cancer syndromes. The role of P53
      mutations in the program of carcinogenic genetic alterations differs among tumor
      sites ranging from the earliest mutations that can be detected in premalignant
      cells to mutations that trigger malignant transformation of a benign neoplasm.
      P53 mutations can cause expression of abnormal proteins or result in complete
      absence of P53 expression. For these reasons the role of P53 genetic disruption
      has different implications in different tumor types and may vary depending on the
      effect of the mutation on P53 protein function. Immunohistochemical detection of
      P53, commonly used as a surrogate for identification of a mutant gene, has
      imperfect sensitivity and specificity, further complicating correlations between
      P53 gene status and clinical outcomes. The presence of P53 mutations has been
      shown to affect prognosis of some cancers. The identity of P53 mutations can be
      used to determine tumor clonality. The detection of P53 mutations suggests the
      severity of premalignant lesions. Evolving technology for more accurate
      identification of P53 mutations, better understanding of the function of mutant
      P53 protein, and more detailed analysis of individual tumor types may expand the
      relevance of P53 gene analysis for clinical outcomes and therapeutic response.

PMID- 12063679
TI  - Prostate-specific antigen in prostate cancer: a case study in the development of
      a tumor marker to monitor recurrence and assess response.
AB  - The serum marker known as prostate-specific antigen (PSA) has established itself
      as the most important tool for the early detection of prostate cancer. However,
      more recent data indicate that (post-treatment) PSA and PSA kinetics can be used
      to predict the outcome of a variety of therapeutic interventions including
      radical prostatectomy, radiation therapy, androgen deprivation, and treatment of
      hormone-refractory prostate cancer. PSA recurrence after radiation therapy is now
      accepted as a harbinger of developing metastatic disease. The American Society
      for Therapeutic Radiation Oncology (ASTRO) consensus definition is the most
      widely accepted definition of failure after radiation therapy. Rather than using
      a specific PSA cutoff, three consecutive PSA rises was felt to be a more reliable
      indicator of biochemical failure. The PSA nadir (the lowest PSA level achieved
      after therapeutic intervention) also appears to correlate with the likelihood of
      remaining disease-free. Similarly, a rapid doubling time is a significant
      predictor of developing distant metastases. The most appropriate definition for
      biochemical (PSA) failure following radical prostatectomy is usually considered
      to be a non-zero value. As is the case after radiotherapy, there appears to be a
      relationship between the rate of rise of the PSA and the risk of distant failure
      following radical prostatectomy. In patients with metastatic disease, multiple
      studies appear to indicate that a fall in PSA, however measured, appears to be
      predictive of improved outcome in prostate cancer patients treated with androgen
      deprivation. Multiple reports of trials in the treatment of hormone-refractory
      prostate cancer (HRPC) appear to substantiate the observation that patients who
      have a greater than 50% decline in PSA have an improved survival. Correlation of
      PSA declines with other markers of clinical benefit, including clinically
      significant "subjective" end points such as pain control, have strengthened the
      argument that a PSA decline can serve as an intermediate endpoint in clinical
      trials involving HRPC patients.

PMID- 12063680
TI  - Pathological and molecular assessment of sentinel lymph nodes in solid tumors.
AB  - Sentinel nodes (SNs) are the first set of nodes to receive drainage and cancer
      cells from a primary tumor. While there may be a single SN, frequently there are
      one to three or more SNs. The development of sentinel node surgery over the last
      decade has led to dramatic changes in the surgical approach to regional nodes
      draining solid tumors. The surgeon can now identify, to a level of accuracy
      previously impossible, the regional nodes most likely to be involved with cancer
      in any individual patient. This new capability comes at a cost; the principles
      guiding the extent of nodal surgery must be completely re-examined. The extent of
      surgical resection required to achieve each of the goals of regional node surgery
      (1) establishing prognosis, (2) obtaining regional control, and (3) improving
      overall survival-may no longer be simply the default "regional node resection"
      and may vary depending on the clinical goals. Inseparable from this new surgical
      technology is the methodology employed for pathologic evaluation of SNs. It is
      critical that pathologists and clinicians conduct definitive clinical research
      directed toward defining the role and impact that SN surgery has on each of these
      surgical goals.

PMID- 12063681
TI  - Challenges in developing a molecular characterization of cancer.
AB  - DNA microarrays are widely used to measure gene expression across thousands of
      genes in parallel. Recently, considerable efforts have been made to utilize this
      technology to improve our understanding of cancer and to identify novel
      diagnostic markers and therapeutic targets. Here, we detail some of the
      challenges in developing a molecular characterization of cancer and in
      translating these new discoveries towards clinical utility.

PMID- 12063682
TI  - Doctor's dilemma: incorporating tumor markers into clinical decision-making.
AB  - Physicians are often faced with the dilemma of how to incorporate tumor markers
      into routine clinical decision-making. Tumor markers may influence clinical
      decisions at various stages of cancer therapy: screening, diagnosis, prognosis,
      detection of early relapse, and monitoring of therapy. We use the examples of
      beta-human chorionic gonadotrophin (beta-HCG) and alpha-fetoprotein (AFP) as
      markers for germ cell tumors (GCT), and prostate-specific antigen (PSA) as a
      marker for prostate cancer, to illustrate their use and limitations for these
      purposes. We then focus on monitoring and choice of treatment by presenting three
      vignettes; these highlight the potential benefits and problems associated with
      the use of tumor markers for monitoring and detection of early relapse in
      asymptomatic patients.

PMID- 12063683
TI  - Regulatory issues in tumor marker development.
AB  - The Food and Drug Administration (FDA) has been actively involved in oversight of
      medical devices, including in vitro diagnostic devices (IVDs) since the passage
      of the Medical Device Amendments of 1976. A variety of both premarket and
      postmarket regulatory controls were put into place as a result of this new
      program. The type of oversight applied to tumor markers available for marketing
      in the United States depends on both the intended use of the test and the manner
      in which it is being commercialized-whether offered as a test kit or system or as
      a laboratory testing service. Tumor markers may be reviewed as 510(k) submissions
      or as premarket approval application (PMA) submissions or may be exempt from
      premarket reviews. The FDA works hard to maintain an appropriate balance in its
      oversight activity and to ensure that its mission is focused on activities
      designed to promote public health.

PMID- 12063684
TI  - [BSE virus in the tonsils?].

PMID- 12063685
TI  - [Tonsil biopsy in early diagnosis of variant Creutzfeldt-Jakob disease].

PMID- 12063686
TI  - [Disposable instruments in tonsillectomy--Great Britain makes the first step].

PMID- 12063687
TI  - [Quality of life of patients with carcinomas of the mouth cavity].

PMID- 12063689
TI  - [Transmission of spongiform encephalopathies (prion diseases)].
AB  - The transmissible spongiform encephalopathies (TSE), or prion diseases,
      constitute a form of degenerative disorders of the central nervous system, which
      are characterized by a typical spongiform histological pattern and a fatal
      course. According to Prusiner's theory, its agent consists of a protein without
      any nucleic acid, the "proteinaceous infectious agent", or prion. This is a
      pathologically folded form of the normal prion protein (PrPC), and then called
      PrPSc. TSE are observed in different mammals including humans. In humans, they
      include Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker syndrome
      (GSS), fatal familial insomnia (FFI), Kuru and the new variant of the Creutzfeldt
      Jakob disease (vCJD). The longest known TSE is scrapie in sheep. Since 1984 the
      bovine spongiform encephalopathy (BSE) and since 1996 the variant Creutzfeldt
      Jakob disease have been documented. This paper gives an overview on the
      pathogenesis, epidemiology and the clinical features of the different prion
      diseases.

PMID- 12063688
TI  - [Variant Creutzfeldt-Jakob disease. Epidemiology, detection, diagnosis and
      prevention with special reference to minimizing risk of iatrogenic transmission
      by medical products, especially surgical instruments. Report of the Variant
      Creutzfeldt-Jakob Disease Task Force on this topic].

PMID- 12063690
TI  - [Diagnosis of prion diseases].
AB  - Prion diseases are histologically characterized by a spongiform encephalopathy.
      The early symptoms of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt
      Jakob disease (vCJD) are unspecific. To date, the definite diagnosis can only be
      made by histological examination of central nervous tissue, i.e. brain biopsy or
      post mortem. Therefore, diagnostic tests are being elaborated that suffice with
      cerebrospinal fluid or blood. Unlike the sporadic form of Creutzfeldt-Jakob
      disease, that involves the central nervous system exclusively, in the variant of
      the Creutzfeldt-Jakob disease the lymphoreticular system including the tonsils is
      involved, too. Hence, a tonsillar biopsy can be performed instead of a brain
      biopsy. In particular, the diagnostic criteria of both CJD and vCJD are
      described.

PMID- 12063691
TI  - [Clinical aspects of abscess development in parotitis].
AB  - OBJECTIVE: The purpose of this paper was to analyse parotideal abscesses on the
      basis of a larger number of patients. PATIENTS AND METHODS: The data of 36
      patients (mean age 44 years) with a parotideal abscess was analysed. RESULTS:
      Ultrasound scan was always necessary to verify the diagnosis. The surgical
      drainage was done under myoelectric monitoring of the facial nerve. Only in 1
      patient a temporary minor paralysis of the mandibular branch was noticed. The
      most common bacteria were Staph. aureus, Streptococcus, and Peptostreptococcus.
      In 2 cases a tuberculosis and in 2 children an atypical mycobacterial infection
      was discovered. In another patient a metastasis of a squamous cell carcinoma was
      found. CONCLUSIONS: In every patient with an acute swelling of the parotid region
      without consideration of age, number of leucocytes or a typical fluctuation, an
      ultrasound scan should be used. The surgical drainage of the abscess should be
      done under myoelectric monitoring (Cave: muscle relaxant). In every case, a
      specimen for microbiological analysis (bacterial determination) and a biopsy (to
      exclude malignoma or atypical mycobacteria) are necessary. A peri- and post
      operative therapy with a combination of aminopenicillin and clavulanic acid or
      with cephalosporine is recommended.

PMID- 12063692
TI  - [Reconstruction of the frontal bone with individual titanium implants after
      surgical therapy of osteomyelitis of the frontal bone].
AB  - Individually prefabricated titanium implants enable the reconstruction of the
      frontal bone after surgical therapy of osteomyelitis without compromising
      mechanical stability or aesthetic results. Primarily the infected bone tissue is
      removed. Helical computed tomographic systems are used for the aquisition of
      patient data. After being transmitted to a computer aided design system (CAD
      system) this data is used for construction of the implant geometry using freeform
      surfaces. The outer surface contour is derived from the contours of the bone
      defect. The completed computer-based implant design is finally transformed into
      control data to run the milling machine which produces the implant from a block
      of titanium. Modern industrial CAD/CAM-technology allows standardized
      prefabrication using data from CT-scans. The precision of all implants was
      predictable and duration of the reconstructive procedure could be reduced. During
      postoperative follow-up (5-24 months) no loss of implant or recurrence of the
      osteomyelitis could be observed.

PMID- 12063693
TI  - [A concept for the assessment of quality of life in patients with carcinomas of
      the upper aerodigestive tract].
AB  - BACKGROUND: The quality of life (QoL) of patients with malignant diseases
      decreases significantly. OBJECTIVE: The evaluation of QoL is generally not part
      of the management of patients with head and neck cancer. The aim of this study
      was to develop an additional disease- and treatment-specific questionnaire to
      evaluate QoL in surgically treated head and neck cancer patients. PATIENTS AND
      METHODS: The general QoL was evaluated with the QLQ-C30 questionnaire developed
      by the European Organisation of Research and Treatment of Cancer (EORTC).
      RESULTS: The disease-specific QoL was evaluated using the EORTC H&N35 module. The
      new questionnaire "Kiel Head and Neck 17" (KQL H&N-17) is a disease- and
      treatment-specific addition especially in regard to side effects caused by
      surgical treatment. CONCLUSIONS: A wide application of this whole concept is
      needed to obtain comparable results from studies suitable for evaluating QoL in
      patients receiving different treatments for their malignant diseases. Moreover,
      the effectiveness and quality of treatment could be controlled better, which
      would help to increase the QoL of these patients.

PMID- 12063694
TI  - [Massive Gorham-Stout osteolysis of the temporal bone and the craniocervical
      transition].
AB  - Massive osteolysis Gorham-Stout is a rare, benign but locally aggressive
      angiomatosis which results in destruction and resorption of bone. The etiology
      and pathogenesis are undefined. The occurrence of the disease in the skull base
      is uncommon. A 54-year-old female presented with isolated, one-sided surditas.
      Eight years before the patient underwent surgery and radiation therapy for
      treatment of hypopharyngeal cancer. A transtemporal biopsy was taken and a highly
      vascularized, cystic lesion with destruction of the right occipital and temporal
      bone and the atlas was found. Histopathology showed thin-walled capillaries with
      flattened endothelial lining cells. After exclusion of malignant and infectious
      components the diagnosis of Gorham's disease was established. Review of the
      literature suggests radiation therapy as the method of choice for stopping the
      disease's progress. The aim of this case report is to emphasize the Gorham-Stout
      Syndrome as a rare differential diagnosis for skull base lesions.

PMID- 12063695
TI  - [Myositis proliferans. Differential cervical space-occupying lesion diagnosis].
AB  - Myositis proliferans is a rare and benign pseudosarcomatous tumour of soft
      tissue. In most cases it is found in the region of the shoulder and arm and its
      occurrence in the region of the neck is described in literature in 16 cases in
      all. For the ear, nose and throat specialist it is an important differential
      diagnosis in contrast to malignant tumours. In this report we present the cases
      of two patients, who were suffering from painful cervical swelling that had been
      increasing for some days. The problems inherent in the diagnosis of this illness
      are discussed. Due to its rapid growth the tumour is generally falsely diagnosed
      and radically removed. Therefore, in appropriate case history, this possibility
      should be considered and excluded in order to prevent the patient from
      unnecessary radical operation. In addition to clinical symptoms, imaging and
      trial excision are suitable.

PMID- 12063696
TI  - [Polypoid space-occupying lesion of the nasopharynx. Nasopharynx tuberculosis
      with cervical lymph node involvement bilaterally and right hypoglossal
      paralysis].

PMID- 12063697
TI  - [BSE and vCJD. Relevance for the established ENT physician].

PMID- 12063698
TI  - [Indications for neck operation in undiagnosed lymph node metastases. 2. Neck
      dissection in the clinical N0 neck].

PMID- 12063699
TI  - [Response to the contribution by R. Buchwalski--"A plea for re-use of heart
      catheters based on 25 years of personal experience"].

PMID- 12063700
TI  - [Chlamydia pneumoniae and cytomegalovirus in degenerative aortic valve stenoses].
AB  - Recent evidence suggests a causal relationship between inflammatory as well as
      infectious pathomechanisms and valvular degeneration. Based on the concept of
      chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infections, and of
      variable stressors working on valvular microecology, the present study sought to
      assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of
      CMV, of macrophages and of the human homologue hHSP60. Serial sections of high
      grade degenerated native (n = 16) and prosthetic (n = 6) aortic valves were
      analyzed by immunohistochemistry for the presence of these determinants.
      Degenerated aortic valves revealed prevalence of Chlamydia pneumoniae in 41% (10
      of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64%
      (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were
      predominantly found in valvular fibrosa; CMV showed a second predilection site at
      the ventricular luminal border. Both microorganisms revealed a strong correlation
      between each other (r = 0.73; p < 0.001) as well as with hHSP60 (cHSP60: r =
      0.74; p < 0.001; CMV: r = 0.80; p < 0.001). Macrophage infiltration correlated
      with cHSP60 (r = 0.78; r < 0.001), CMV (r = 0.78; r < 0.001) and hHSP60 (r =
      0.56; r = 0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was
      increased more than 5-fold in prosthetic valves compared to native valves (p =
      0.017, p = 0.002 and p = 0.005). In summary, valvular infections of Chlamydia
      pneumoniae and of cytomegalovirus are frequently seen in degenerated aortic
      valves, irrespective of native or prosthetic origin. Colocalization of both HSP60
      homologues and cytomegalovirus within macrophages in valvular fibrosa points to
      regional stressor effects that might be at least partly attributable to chronic
      persistent pathogen burden and molecular mimicry.

PMID- 12063701
TI  - [Anticoagulation in pregnant women after artificial heart valve replacement: is
      low-molecular-weight heparin an alternative?].
AB  - We report on the case of a 24-year-old pregnant woman with acute mechanical
      mitral valve thrombosis due to a treatment failure of low molecular weight
      heparin (LMWH) for permanent anticoagulation following mechanical valve
      replacement. Initially, our patient was put on oral warfarin for anticoagulation,
      but when her pregnancy was perceived the anticoagulation regimen was switched to
      daily subcutaneous administration of LMWH in order to minimize the risk of
      warfarin-induced embryopathy. During her 24th week of gestation she developed
      acute life-threatening pulmonary edema and hemodynamic instability, which was
      caused by an acute thrombosis of her artificial mitral valve. In an emergency
      operation the thrombozed valve was replaced by a porcine biological heart valve.
      The patient recovered uneventfully and gave birth to a healthy child in her 35th
      gestational week by cesarean section. In addition we discuss the rationale of
      different anticoagulation regimens with regard to maternal and fetal outcome with
      special consideration of LMWH as an alternative strategy to oral anticoagulation
      during pregnancy in women with mechanical heart valves.

PMID- 12063702
TI  - [Interventional occlusion of interatrial communication after modified Fontan
      operation].
AB  - After modified Fontan operations various communications between the systemic and
      pulmonary venous returns may cause persistent or increasing postoperative
      cyanosis. Interventional closure of these right-to-left shunts may be necessary
      to eliminate hypoxemia and to reduce the risk of paradoxical embolic
      complications. PATIENTS AND METHODS: Eighteen patients with a mean age of 5.6 +/-
      4.1 (2.5-17.5) years underwent interventional closure of a right-to-left shunt
      17.4 +/- 15.8 (3-60) months after a modified Fontan operation. After test balloon
      occlusion fenestrations were closed in 13 patients using an Amplatzer Septal
      occluder (n = 7), a Rashkind PDA occluder (n = 3), a CardioSeal umbrella (n = 1)
      and detachable coils (n = 2). Residual leaks at the suture lines between the
      interatrial patch and the right atrial wall were closed using detachable coils
      and a Rashkind PDA occluder in 2 and 1 patients, respectively. In 3 patients
      intracardiac venous collateral channels were closed by means of detachable coils.
      RESULTS: The mean aortic oxygen saturation increased from 85 +/- 4.5 (70-89)% to
      91.4 +/- 2.8 (83-95)% (p < 0.001) breathing room air and the mean tunnel pressure
      rose from 10.7 +/- 1.8 (6-14) mmHg to 12.1 +/- 2.4 (6-16) mmHg (p < 0.001).
      Calculated Qs decreased from 5.15 +/- 2.1 (2.1-11.3) l/min/m2 to 3.6 +/- 1.0 (1.8
      5.6) l/min/m2 (p < 0.001). Mixed venous saturation (66.4 +/- 7.4% vs 65 +/- 7%)
      and mean systemic arterial pressure (73 +/- 8 mmHg vs 73 +/- 9 mmHg) remained
      unchanged. In one patient an additional leak of the tunnel could not be closed
      because of an increase to more than 18 mmHg of the mean pressure in the lateral
      tunnel during balloon test occlusion. In 2 patients residual leaks after umbrella
      and coil occlusion of a fenestration and an additional venous collateral channel
      were closed by means of coils after 16 and 21 months, respectively. At a follow
      up of 42 +/- 23 (7-99) months, mean oxygen saturation measured by pulse oxymetry
      was 93 +/- 2 (90-97)%. In 2 patients color-coded Doppler echocardiography
      revealed a minimal residual right-to-left shunt. In 2 patients contrast
      echocardiography demonstrated the additional presence of intrapulmonary fistulas.
      All patients remained free from device migration, thromboembolic events and
      hemolysis. CONCLUSION: After modified Fontan operations various right-to-left
      shunts between the systemic and pulmonary venous returns can be successfully
      closed using umbrella devices or coils to eliminate cyanosis and to reduce the
      risk of paradoxical embolism.

PMID- 12063703
TI  - Effects of the Ca2+ sensitizers EMD 57033 and CGP 48506 on myocardial
      contractility and Ca2+ transients in human ventricular and atrial myocardium.
AB  - Ca2+ sensitizers like EMD 57033 (EMD) and CGP 48506 (CGP) may be advantageous for
      the treatment of human heart failure, as they increase force of contraction
      without increasing the intracellular Ca2+ transients or energy consumption.
      However, whether or not Ca2+ sensitizers differ in their mode of action in human
      myocardium is not fully understood. The present study investigates the influence
      of EMD and CGP on force of contraction (FOC) and the intracellular Ca2+ transient
      (fura-2 ratio method) in left ventricular papillary muscle strips from left
      ventricular failing human myocardium (DCM, n = 28) as well as in right atrial
      trabeculae (RA, n = 21) obtained from patients undergoing cardiac bypass surgery.
      In isolated trabeculae of DCM, FOC was more efficacious and potently increased
      after application of EMD (EC50 EMD: 4.7 +/- 1.0 mumol/l, max. PIE EMD: + 12.0 +/-
      2.0 mN/mm2) than CGP (EC50: 16.9 +/- 7.6 mumol/l, max. PIE: +6.4 +/- 2.8 mN/mm2).
      Similar results were obtained in RA. Application of carbachol (100 mumol/l) had
      no effect on the positive inotropic effect of EMD or CGP. Both Ca2+ sensitizers
      significantly increased time to half peak relaxation as well as diastolic tension
      in DCM. EMD (10 mumol/l) and CGP (30 mumol/l) did not affect the Ca2+ transients
      in RA. The Ca2+ sensitizers EMD and CGP increase cAMP and Ca2+ independently from
      the force of contraction in the human myocardium. However, their therapeutic use
      in human heart failure may be limited as they impair relaxation.

PMID- 12063704
TI  - [Survival, clinical data and quality of life 10 years after heart
      transplantation: a prospective study].
AB  - AIM: To study prospectively patients after heart transplantation with respect to
      quality of life, mortality, morbidity, and clinical parameters before and up to
      10 years after the operation. METHODS: Sixty patients (47.9 +/- 10.9 years, 57
      men, 3 women) were transplanted at the University of Vienna Hospital, Department
      for Heart and Thorax Surgery and were included in this study. They were assessed
      when set on the waiting list, then exactly one, 5 and 10 years after the
      transplantation. The variables evaluated included physical and emotional
      complaints, well-being, mortality and morbidity. In the sample of patients who
      survived 10 years (n = 23), morbidity (infections, malignancies, graft
      arteriosclerosis, and rejection episodes) as well as quality of life were
      evaluated. RESULTS: Actuarial survival rates were 83.3, 66.7, 48.3% at 1, 5, and
      10 years after transplantation, respectively. During the first year, infections
      were the most important reasons for premature death. As a cause of mortality,
      malignancies were found between years 1 and 5, and graft arteriosclerosis between
      years 5 and 10. Physical complaints diminished significantly after the operation,
      but grew significantly during the period from 5 to 10 years (p < 0.001). However,
      trembling (p < 0.05) and paraesthesies (p < 0.01) diminished continuously.
      Emotional complaints such as depression and dysphoria (both p < 0.05) increased
      until the tenth year after their nadir at year 1. In long-time survivors, 3
      malignancies (lung, skin, thyroidea) were diagnosed 6 to 9 years postoperatively.
      Three patients (13%) had signs of graft arteriosclerosis at year 10; 9 (40%)
      patients suffered from rejection episodes during the course of 10 years. There
      were no serious rejection episodes deserving immediate therapy. Quality of life
      at 10 years is good in these patients. CONCLUSIONS: Heart transplantation is a
      successful therapy for patients with terminal heart disease. Long-term survivors
      feel well after 10 years and report a good quality of life.

PMID- 12063706
TI  - [Space occupying lesion of unknown origin in the pulmonary trunk: targeted
      differential diagnosis and surgical therapy in a patient with B symptoms and
      thoracic pain].
AB  - Leiomyosarcomas are only rarely found in routine cardiac surgery. For the patient
      they hold, however, a very high-risk potential as only an early diagnosis, and
      immediate surgical therapy leads to long-term survival. Awareness, timely
      diagnosis, and immediate radical surgical therapy is imperative. This report
      describes the case of a 21-year old male with a strong suspicion of
      leiomyosarcoma of the pulmonary artery. Due to his clinical symptoms, the patient
      was transferred to operation immediately after completion of all diagnostic
      measurements. Postoperatively the diagnosis of a leiomyosarcoma proved to be
      false; instead a rare fibro-histologic tumor was found. Even in the case of a
      suspected leiomyosarcoma, rapid and radical surgical therapy is imperative due to
      the poor prognosis of leiomyosarcoma.

PMID- 12063705
TI  - [Physical training as interval or continuous training in chronic heart failure
      for improving functional capacity, hemodynamics and quality of life--a controlled
      study].
AB  - We conducted a three-week randomized trial comparing the improvement of
      functional capacity by exercise training in chronic heart failure by the steady
      state (EF 27.3%, n = 20) and the interval modus (EF 29.3%, n = 20) with a control
      group (EF = 26.6%, n = 10). Minimal EF was 10%, the lowest maximal oxygen
      consumption was 9.3 ml/kg/min and the lowest cardiac output was 1.9 l/min; 9
      patients had been evaluated for HTX. VO2 at the anaerobic threshold and at
      maximal exercise increased in the continuous exercise group by 1.4 or 1.6
      ml/kg/min, respectively, corresponding to an increase of 13.7% (p < 0.05) and
      9.3% (p < 0.05). In the interval training group the increase was 1.3 and 1.5
      ml/kg/min corresponding to 14% (p < 0.05) and 8.1% (p < 0.05). Continuous short
      term exercise had no impact to central hemodynamics as pulmonary artery pressure
      (PA), capillary wedge pressure (pc), cardiac index (CI) or stroke volume index
      (SVI), whereas after interval training a significant increase at maximal exercise
      could be seen in CI (p < 0.05) and SVI (p < 0.01) with a concomitant drop in
      systemic peripheral resistance (p < 0.05) compared to the steady-state modus.
      Interval training was further characterized by a higher short-term but lower mean
      work load with a significantly smaller increase in lactate. Quality of life was
      improved according to the SF-36 questionnaire in both training groups but the
      psychologic sum factor was three times as high, increasing to 24.2% in the steady
      state exercise group. It can be concluded that clinically stable patients with
      heart failure and even those already having been evaluated for cardiac
      transplantation profit from short-term physical training. Both training
      modalities seem equally suited to improve functional capacity. However interval
      training leads to more pronounced improvement in hemodynamics compared to the
      steady-state exercise, whereas the later had a greater impact on psychological
      well-being and quality of life. Patients with heart failure and severe peripheral
      deconditioning tolerate higher workloads with more peripheral stress by an
      interval training modus. Long-term training modalities need to be established to
      further improve and stabilize functional status.

PMID- 12063707
TI  - [Cerebral embolism as the first manifestation of left ventricular metastatic
      bronchial carcinoma].
AB  - Commonly the diagnosis of cardiac metastases in extracardiac cancer is difficult
      because of predominant symptoms of the underlying disease. In the reported case,
      a cerebral embolization was the first manifestation of a bronchogenic carcinoma
      with left ventricular metastasis. A 58-year-old male patient was admitted to the
      hospital with symptoms of an incomplete left-sided hemiparesis that occurred
      without prodromi. Other clinical abnormalities were not found. The two
      dimensional echocardiogram showed a small space-occupying lesion in the left
      ventricle. Clinical symptoms completely disappeared within 3 days of heparin
      therapy. In order to prevent repeated embolization (after angiographic exclusion
      of coronary stenoses), the tumor was excised by cardiac surgery. In the
      histologic examination, malignant tumor cells were found. As primary origin, a
      small peripheral bronchogenic carcinoma with (clinically silent) additional
      metastases to the left adrenal gland and the right pelvic bone was found. The
      patient died 7 months later because of progressive metastatic cancer disease.
      Thus (on one hand) the reported case underlines the value of echocardiographic
      examination in suspected heart manifestation of cancer disease. On the other
      hand, in patients with heart tumors prior to curative therapy, additional
      diagnostic procedures (such as CT or MRI) should be performed in order to detect
      extracardiac tumor manifestations.

PMID- 12063709
TI  - [Epithelioid hemangioendothelioma of the heart in association with
      myelodysplastic syndrome].
AB  - The case of a primary cardiac epithelioid hemangioendothelioma (EHE) arising
      multifocally in the papillary muscle of the tricuspid valve and the deeper
      trabecular muscle in a 68-year-old male with myelodysplastic syndrome is
      presented. The tumor was an incidental autopsy finding. Histologically the tumor
      is characterized by proliferation of plump epithelial-like endothelial cells with
      the vascular differentiation being mostly expressed at a cellular level in the
      form of cytoplasmic vacuoles. In the differential diagnosis, metastatic
      carcinoma, cardiac myxoma as well as other epithelioid vascular neoplasms should
      be considered. EHEs are indolent tumors of intermediate malignancy with the
      potential to metastasize, even after a long time. Primary cardiac EHE is
      extremely rare. To our knowledge, only four EHEs of the heart have been reported
      in the literature. We believe, this is the first report of a cardiac EHE in this
      localization and the first one in association with myelodysplastic syndrome.

PMID- 12063708
TI  - [Primary Burkitt lymphoma of the heart--diagnosis and therapy].
AB  - An 85-year-old patient suffered from progressive deterioration (NYHA III) for
      several months. Cardiac disease was suspected. Echocardiography as well as a CT
      scan of the heart revealed a heart tumor to be the cause. Tumor staging was
      negative. After transvenous biopsy, the diagnosis of a Burkitt lymphoma could be
      established. Due to the advanced age of the patient, the intended surgical
      therapy was turned down and the patient was treated with 6 courses of a
      potentially therapeutic chemotherapy (CHOP scheme), which was well tolerated by
      the patient. The following CT scan showed a complete remission of the tumor. Six
      months after chemotherapy the patient is in NYHA stage I.

PMID- 12063710
TI  - [Cardiomyopathy associated with uncontrolled self medication of anabolic
      steroids].
AB  - Though doping has become increasingly ostracized in the context of professional
      sports, an enormous number of unrecorded cases must be assumed in semi
      professional competitive sports as well as in popular sports. This holds
      especially true for those forms of sports which are done in order to obtain a
      well-proportioned, athletic, healthy looking body. This case report describes a
      formerly healthy young man who had to be urgently admitted to an intensive care
      unit due to severe myocardial pump failure. As anamnestic information was
      insufficient and inadequate, the taking of anabolic steroids in high doses was
      proven, as their metabolites could be detected by urine analysis. Until now,
      myocardial contractile dysfunction has persisted for more than twelve months
      after the initial admission. Though other diagnoses which might have led to this
      impaired myocardial contractile performance have been excluded, cardiomyopathy
      associated with the taking of anabolic steroids must be assumed. Even in non
      professional and public sports, a widespread abuse of doping substances exists.
      Hence, cardiomyopathy associated with the misuse of anabolic steroids has to be
      considered especially in young, formerly healthy patients.

PMID- 12063711
TI  - ["Memory, speak..." (3). "Quo vadis cardiopathologia?"].

PMID- 12063712
TI  - [Risk management in anesthesiology--a continuing challenge].

PMID- 12063713
TI  - [Man at risk. Preventive strategies and risk management for patient safety].
AB  - Anaesthesia-related risk has been significantly reduced within the last decade.
      Nevertheless the risk and the possibility of dying or suffering permanent damage
      still exist. To improve patient safety, risk assessment and analysis must lead to
      the development of preventive strategies. For this purpose anaesthesia can rely
      on the concepts of other "high reliability" organisations such as aviation or
      nuclear power plants. Analyses of critical incidents in the different fields
      confirm that next to technical problems human factors account for most of the
      preventable mishaps. Human factors are responsible for individual mistakes as
      well as for organisational errors. Therefore besides traditional concepts of risk
      reduction (e.g. guidelines) new strategies (e.g. full-scale simulation) must be
      applied to minimise the negative impact of human factors on patient safety. Risk
      management has to consider technical, organisational and human factors to
      implement a higher standard of patient safety.

PMID- 12063714
TI  - [Postoperative pain therapy in Germany].
AB  - OBJECTIVE: A survey was performed to obtain information on the organization and
      practice of postoperative pain management. METHODS: A questionnaire was mailed to
      773 directors of German departments of anesthesiology. RESULTS: A total of 446
      replies (57.7%) could be analyzed. Of the departments, 161 (36.1%) had
      established an acute pain service (APS), more often in hospitals > or = 1000 beds
      (63%) than in hospitals with 400-999 beds (40%) and hospitals with < 400 beds
      (27%). Epidural analgesia was practiced in 97% of the departments, however, it
      was the analgesic technique of choice for larger abdominal surgery or amputation
      of the lower limb only in 60.8% and 45.5% of the departments, respectively.
      Departments with APS provided epidural analgesia more often on general wards than
      departments without APS (88.2% vs. 68.4%, p < 0.01). Technically more challenging
      methods (e.g. catheters for regional anesthesia, PCA, PCEA) were more often
      provided in hospitals running an APS (p < 0.001). CONCLUSIONS: The number of
      departments with APS has increased over the last 10 years. Future decisions on
      reimbursement should consider this extensive service.

PMID- 12063715
TI  - [Hemodynamic, endocrinological and psychological investigations on subjects
      during helicopter flights].
AB  - PURPOSE: The emergency transport in an ambulance can be a considerable physical
      and psychological stress for the patient. In this article we report on a stress
      test with 23 volunteers transported in an emergency helicopter. METHODS: We
      determined the hemodynamic and endocrinological values of 23 volunteers after a
      standardised 15-minute transportation in a helicopter type EC 135. RESULTS:
      During the take-off we registered an increase of the heart rate of 18% and
      endocrinological parameters were elevated up to 51%. All the registered values
      were within the physiological tolerance level. Psychological tests showed a
      feeling of fear and agitation before take-off, but after the flight the
      volunteers reported less stress than expected. CONCLUSION: The stress situation
      is caused by fear of the flight, that cannot be objectively justified. The
      relatively low stress induction by helicopter transportation might be an
      indication that there should be more patient transport with modern helicopters,
      especially for non-trauma patients. This subject deserves further investigation.

PMID- 12063716
TI  - [Postoperative morphine excess or rational therapy? An exceptional case of
      applying the morphine equivalent].
AB  - We report on a 51-year-old female with a 7 year history of breast cancer. In
      August 2000 surgical replacement of the 8th thoracic vertebra was performed. From
      November 2000 the patient developed progressive pain, due to additional spine
      metastases, leading to pain therapy (according to the patient record) as follows:
      MST 320 mg oral 4 times daily, Durogesic 100 micrograms/h transdermal, Sevredol
      40 mg oral 3 times daily and Ibuprofen 800 mg oral 3 times daily. Due to the risk
      of spinal instability and persisting pain a thoracic spondylodesis from Th 4-L2
      was performed. Parallel to arrival in the PACU the patient developed extremely
      intensive pain. Pain control was achieved by fractional injection of overall 660
      mg morphine in the first 120 min. After interviewing the patient, opioid
      consumption surprisingly turned out to be 60% higher than presumed. Pain therapy
      was continued by infusion and PCA with morphine in a daily intravenous dosage of
      600-800 mg. Consecutively the pain therapy was switched to oral morphine and co
      analgesics and the patient was discharged home 14 days postoperatively. PROBLEM:
      Some patients with chronic cancer pain are used to increased opioid dosages prior
      to planned surgery. In the perioperative setting these dosages have to be
      continued and adapted to current requirements, otherwise analgesic undersupply
      occurs. In our case report we describe a serious sequence of postoperative
      analgesic undersupply in an opioid consuming patient. The main principles of post
      operative dosing and logistic pitfalls are illustrated.

PMID- 12063717
TI  - [Opioid intoxication following transdermal administration of fentanyl].
AB  - The case of a 77-year-old woman is described, who was found unconscious, with
      decreased respiration and miotic pupils, having previously experienced dizziness,
      nausea and drowsiness before. In the emergency room a fentanyl patch was
      detected, which had obviously been mistakenly applied by the patient the day
      before. Opioid intoxication was assumed and successfully treated with naloxon.
      The patient was supervised in an ICU for 24 h and sent home the next day without
      serious sequelae. The consequences following inappropriate use of transdermal
      fentanyl are discussed.

PMID- 12063718
TI  - [Pain and opioids in preterm and newborns].
AB  - Despite the fact that neonates and infants are not capable of expressing their
      subjective pain sensations, it has become clear that they do perceive
      nociception, as pain correlates to hormonal, metabolic, immune, and
      cardiovascular changes. New findings support the notion that repetitive painful
      stimuli result in long term psycho-physiological effects with ensuing decreased
      attentiveness and orientation, poor regulation of behavioral state and motor
      processes, increase in irritability as well as an altered pattern of feeding and
      sleeping. These sequelae of repetitive painful experiences with an increase in
      sensitization of sensory afferent input supports the view of a sufficient
      analgesia during all kinds of painful procedures in the preterm and neonate. In
      order to sufficiently diminish nociceptive afferent input during surgery opioids
      are the drugs of choice aside from local anesthetics. However, the use of opioids
      in neonates and especially preterm infants must be considered in the light of
      certain pharmacokinetic and pharmacodynamic differences when compared to adults:
      1. There is a longer elimination rate, which may result in post-operative
      overhang of respiratory depression, especially when opioids are given
      repetitively, resulting in an accumulation and an increased duration of action.
      2. There is a reduced hepatic enzyme activity, which ultimately affects clearance
      rate. 3. The blood-brain-barrier is not fully developed in the preterm, which
      results in more access of opioids to binding sites in the CNS. 4. Differentiation
      of opioid-binding sites into mu, delta, and kappa has not reached its peak; thus,
      higher doses relative to body weight are needed to establish a sufficient deep
      plane of analgesia. 5. Caudal parts of the CNS, especially the pons-medullar
      region exhibit an earlier expression of receptors than the rostral parts.
      Sequelae of such differences are a more pronounced respiratory depression, often
      due to muscular rigidity, and bradycardia after which a full analgesic effect
      takes place. Despite such potential drawbacks, opioids are still the best choice
      as they sufficiently block nociceptive afferent input and when compared to other
      anesthetics, they show the least cardiovascular changes. One, however, has to
      bear in mind that dosing is done according to effect and not to body weight while
      potential side effects are most prominent in the preterm infant.

PMID- 12063720
TI  - [New international guidelines for cardiopulmonary resuscitation as authorized by
      the German Resuscitation Council].

PMID- 12063719
TI  - [The effect of anesthetics on control of respiration].
AB  - Ventilatory control in humans depends on complex mechanisms which aim to maintain
      a cellular CO2-, O2- and H(+)-homeostasis under physiological conditions. This
      regulation is based on chemical control which predominantly acts via peripheral
      chemoreceptors in the carotid bodies and central chemoreceptors in the ventral
      medulla of the brainstem on the one hand, and behavioural control on the other,
      by which it is possible to adapt respiration to conditions of daily living. The
      influence of anaesthesia and related conditions may depress respiration and have
      a sustained effect on ventilatory control. Perioperative respiratory depression
      remains a serious clinical problem in perioperative medicine. This review will
      give an overview of ventilatory control and discuss the most relevant responses,
      describe the effects of pain, anaesthetics and opioids on ventilatory control and
      their interaction. The current body of knowledge is put into perspective to
      identify patients at risk for perioperative respiratory depression.

PMID- 12063721
TI  - [Guidelines of the European Resuscitation Council 2000 on advanced adult life
      support. A statement of the Advanced Life Support Working Group as approved by
      the Executive Committee of the European Resuscitation Council].

PMID- 12063722
TI  - [Guidelines of the European Resuscitation Council 2000 on advanced adult life
      support. A statement of the Advanced Life Support Working Group as approved by
      the Executive Committee of the European Resuscitation Council].

PMID- 12063723
TI  - [Why are substance P(NK1)-receptor antagonists ineffective in pain treatment?].
AB  - The undecapeptide substance P is expressed by primary afferent neurons where it
      is considered to be a cotransmitter of other peptides and glutamate. Since it is
      predominantly found in sensory neurons with unmyelinated fibres (C-fibres),
      substance P has long been thought to be a "pain transmitter". Following
      stimulation of nociceptive afferents, substance P is released in the spinal cord
      and substance P-mediated transmission is primarily brought about by tachykinin
      NK1 receptors. To inhibit this process, a considerable number of non-peptide,
      highly potent, highly selective and brain penetrant NK1 receptor antagonists have
      been developed during the past decade. Experimental studies have proved that NK1
      receptor antagonists are indeed able to blunt pain in sensitized states and thus
      to reverse hyperalgesia, whereas acute pain is left fairly unchanged. The
      hyperalgesic role of substance P has been corroborated by the sensory deficits
      seen in substance P and NK1 receptor knockout mice. However, the concept that NK1
      receptor antagonists would represent a novel class of analgesic drugs, as
      suggested by the preclinical studies, has not been borne out by the clinical
      trials that have been reported thus far. This article offers an overview of those
      hyperalgesic conditions in which NK1 receptor antagonists may be of therapeutic
      value and discusses possible reasons for the discrepancies between preclinical
      and clinical trials with NK1 receptor antagonists.

PMID- 12063724
TI  - [Greater caution using tubes with cuffs. Remarks on the paper "The use of cuffed
      endotracheal tubes in infants and small children" by T. Erb and F. J. Frei
      (Anaesthesist (2001) 50:395-400].

PMID- 12063725
TI  - [Tubes with cuffs in newborn and young children are a risk! Remarks on the paper
      by T. Erb and F. J. Frei (Anaesthesist (2001) 50:395-400].

PMID- 12063726
TI  - [Discussion on cuffed or uncuffed tubes is superfluous. Further remarks on the
      paper by T. Erb and F. J. Frei Anaesthesist (2001) 50:395-400].

PMID- 12063727
TI  - [The cuff alone is no risk factor. Reply to the remarks of L.J. Hoeve, J. Holzki
      and H.J. Schultz-Coulon].

PMID- 12063728
TI  - [The choice of tube size in children].

PMID- 12063729
TI  - [Malignant hyperthermia. General, clinical and experimental aspects].

PMID- 12063730
TI  - [Digital mammography].

PMID- 12063731
TI  - [Physical and technical aspects of digital mammography].
AB  - The establishment of digital mammography systems constitutes a slow process, the
      reason for this being the general need of particular image quality in
      mammography. This article provides an overview of the physical basis of digital
      mammography with high image quality and dose as low as reasonably achievable. The
      trade-off of high contrast resolution and effective quantum efficiency of the
      imaging system on the one hand, and the demand of high spatial resolution or very
      small pixel size on the other hand is discussed. The actual status of the
      available digital detector technology for mammography is described. The digital
      systems presently available are superior to conventional screen-film mammographic
      systems with respect to contrast resolution. An outlook on possible further
      developments in the field of digital mammography is presented.

PMID- 12063733
TI  - [Soft copy versus hard copy findings in digital mammography].
AB  - The advantages of full field digital mammography are the excellent and reliable
      image quality and the reduction of radiation exposure. Image acquisition and
      display are decoupled in digital mammography allowing for optimization of both
      independently. Image displays are currently either hardcopy produced with a laser
      printer or softcopy using a computer monitor. Since the amount of data is high
      the hardware and software must meet specific technical specifications. The
      diagnostic accuracy of softcopy and hardcopy interpretation is comparable if a
      high resolution laser printer and a high quality workstation with high spatial
      and contrast resolution monitors are used. However, using film display the
      potential benefits of digital mammography in terms of manipulation of the data is
      lost. Additional diagnostic benefits might be gained by the combination of
      softcopy display and computer assisted diagnosis (CAD) and telemammography.

PMID- 12063732
TI  - [Digital full field mammography: comparison between radiographic direct
      magnification and digital monitor zooming].
AB  - PURPOSE: Our goal was to compare digital magnification mammograms with images
      zoomed from the digital contact mammogram in patients with microcalcifications.
      PATIENTS AND METHODS: Fifty-five patients with 57 microcalcification clusters
      were evaluated with a FFDM system (Senographe 2000D, GE). In addition to a
      digital contact mammogram, a digital direct magnification mammogram (factor 1.8
      [MAG1.8]) and an image zoomed from the contact mammogram with a magnification
      factor of 1.8 [ZOOM1.8] were obtained in each patient. The image quality (perfect
      = 5 points to inadequate = 1 point) and the characterization of
      microcalcifications (BI-RADS 2-5) were evaluated by 4 readers. The results were
      compared to histopathologic findings in 35 patients (37 lesions) and follow-up in
      20 patients. RESULTS: Histopathology revealed 16 benign and 21 malignant lesions.
      20 patients had benign changes verified by long-term follow-up. Image quality of
      direct magnification FFDM was assessed superior (4.44 points) to zoomed images
      (4.14 points). Sensitivity was superior for direct magnification (97.5%) in
      comparison to the zoomed images (96.3%). However, specificity (MAG1.8: 34.3%,
      ZOOM1.8: 40%), PPV (MAG1.8: 47.5%, ZOOM1.8: 49.8%) and accuracy (MAG1.8: 58.1%,
      ZOOM1.8: 61.2%) were better with zooming technique. Deviation steps from best BI
      RADS assessment were 0.45 for MAG1.8 and 0.44 for ZOOM1.8. CONCLUSIONS: In
      patients with mammographic microcalcifications, monitor zooming of the digital
      contact mammogram is equivalent to direct magnification FFDM. Therefore, monitor
      zooming allows a reduction of the radiation exposure and an optimization of the
      work-flow.

PMID- 12063734
TI  - [Value of CAD systems].
AB  - PURPOSE: Early detection of breast cancer enables for the reduction of mortality.
      The purpose of this article is to describe commercially available systems for
      computer-aided diagnosis (CAD) for mammograms and to analyze their diagnostic
      potential and utility. MATERIALS AND METHODS: Up to now, there are three CAD
      systems available, the Image Checker M 1000 (R2-Technology, USA), the Second Look
      system (CADx Medical Systems) and the Mammex TR (Scanis Inc., USA). Most of the
      present studies are done with the R2-system. The mammographies have been
      digitalized secondarily. Different algorithms recognized microcalcifications and
      masses. The connection between full field digital mammography systems and DICOM
      networks is possible. RESULTS: In retrospective and one large prospective study
      with 12.860 patients it could be shown that sensitivity of the investigator with
      CAD could be improved up to 19%, microcalcifications are yielded with CAD in
      100%, masses in up to 80%. CONCLUSION: Double-reading with CAD-systems can
      increase early breast cancer detection effectively. Regarding the development of
      full field digital mammography we are looking forward to further innovations.

PMID- 12063735
TI  - [Digital full field mammography after breast augmentation].
AB  - PURPOSE: The use of digital full field mammography for imaging augmented breasts.
      METHODS: Images of a sponge, as a tissue equivalent, partly covered with one of
      three different implants (silicone, silicone/saline, saline) were obtained using
      digital and film-screen technique. The visualisation of the sponge structure
      covered by the implant and next to the implant was evaluated by two radiologists.
      Results were compared to clinical results from 35 patients with implants.
      RESULTS: Two images with different parameter settings have to be obtained to
      visualize the covered sponge structure and the structure around the implant with
      film-screen technique. Digital mammography allows assessment of both areas using
      one image at different window settings. The assessability of covered structures
      depends on the type of implant. These results are in keeping with our clinical
      experiences. CONCLUSION: Digital mammography allows equal or better assessment of
      covered and non-covered tissue in augmented breasts without the need for
      additional exposures.

PMID- 12063736
TI  - [Comparison of methods for quantifying contrast enhancement exemplified by
      dynamic MRI mammography].
AB  - AIM: Aim of this study was to demonstrate and compare different quantification
      techniques to assess contrast enhancement in dynamic MRI studies. The diagnostic
      potential of dynamic MRI studies is increasingly appreciated and already used in
      different organ systems. METHOD: A patient population of 314 histologically
      verified breast lesions (138 malignant, 176 benign) were evaluated using a high
      temporal resolved dynamic sequence. Different quantification techniques such as
      the use of a cutoff line, time dependent and pharmacokinetic assessment were
      comparatively evaluated. RESULTS: Time dependent quantification methods revealed
      higher diagnostic potential which was further improved by in vivo normalization
      of the contrast availability in the vascular system. Significant differences in
      the enhancement characteristics were determined between malignant and benign as
      well within the different histological entities. CONCLUSION: Time dependent
      quantification methods enable an angiogenic characterization of lesions to
      improve diagnostic interpretation as well as monitoring during therapy. They are
      also the basis for automated, color-coded visualization of dynamic studies.

PMID- 12063737
TI  - [Optical density of phantom images of different mammography equipment using
      various exposure conditions].
AB  - The requirements for the target value of the mean optical density (o.d.)
      including proper tolerances of mammograms are determined in the "European
      Protocol for the Quality of the Physical and Technical Aspects of Mammography
      Screening (EPMS)". These requirements are not only applicable to screening
      mammography. 22 mammography devices were tested with exposures of test phantoms
      using different kV and thickness of PMMA and with sensitometric step wedges to
      check the processing conditions. Only five of 22 devices fulfill all requirements
      of EPMS to the opt. density. These results are caused by three reasons: first,
      wrong locking of optical density under standard exposure conditions; second,
      wrong compensation of the optical density by the automatic exposure control due
      to varing tube voltage (kV) and PMMA thickness and third, an inadequate back
      coupling to the processing conditions. All tested devices are not conspicuous in
      respect to the results of constancy tests according DIN 6868-2 [2] and DIN 6868-7
      [3]. It is obvious, that the claimed devices are not properly adjusted in the
      acceptance test according DIN 6868-52 (1990-12) [4]. Respectively the tolerances,
      used do not fulfill the requirements to proper density in mammograms.

PMID- 12063738
TI  - [Information on mammography screening--from deception to insight].
AB  - Information about mammography-screening as a basis for informed-decision making
      has to be evidence-based and presented in an unbiased format. This includes
      communication of results about effectiveness/lack of effectiveness of screening
      programmes (breast cancer mortality, total mortality), the quality of mammography
      as a screening test (sensitivity, specificity, positive and negative predictive
      values), and possible harm (consequences of false positive and false negative
      results, overdiagnosis of breast cancer, overtreatment). Outcome data have to be
      communicated as natural frequencies rather than relative differences. In order to
      avoid framing of data equal emphasis has to be put on the proportion of persons
      who are likely to benefit and those who are unlikely to benefit or likely to be
      harmed.

PMID- 12063739
TI  - [Cystic space-occupying lesion of the bursa omentalis].

PMID- 12063740
TI  - [Thyroid gland diagnosis. 1: Diffuse diseases, epithelial bodies].

PMID- 12063741
TI  - [Leflunomide--a new drug for pharmacological immunomodulation].
AB  - The novel immunomodulatory agent leflunomide exhibits a strong anti-inflammatory
      action. This isoxazole derivative is chemically unrelated to any hitherto applied
      immunosuppressants. As a prodrug leflunomide is completely converted to its
      active metabolite A 77 1726 (M1) which blocks the dihydroorotate dehydrogenase, a
      key enzyme of the pyrimidine de novo synthesis. Drug-related adverse effects are
      mild, dose-related and reversible, characterising leflunomide as a safe
      immunosuppressant. While up to now leflunomide has just been approved for therapy
      of rheumatoid arthritis, its mechanism of action affects multiple inflammatory
      pathways, thereby suggesting it to be a potent therapeutic agent in autoimmune
      diseases, graft rejection, and tumour therapy. First dermatological experience
      has been gained in psoriasis and bullous pemphigoid. The role of leflunomide in
      the dermatologist's therapeutic armamentarium will evolve during the next years.

PMID- 12063742
TI  - [St. John's wort (Hypericum perforatum L.). A plant with relevance for
      dermatology].
AB  - Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective
      in the treatment of mild to moderate depression. In traditional folk medicine,
      oily extracts of St. John's wort are used for topical treatment of wounds, burns
      and myalgia. The lipophilic phloroglucin-derivative hyperforin has antibacterial
      and antiinflammatory effects. These effects could be of relevance in topical
      treatment of infected wounds and other dermatoses, but no studies have been
      conducted so far. The naphtodianthrone hypericin is a photodtodynamic active
      substance that kills tumor cells via the induction of apoptosis. Hypericin also
      displays antiviral activity in vitro. In vivo, intravenous or oral treatment with
      hypericin of HIV-infected subjects did not result in a reduction of the virus
      load. Most of the patients treated with hypericin experienced phototoxicity.
      Similar phototoxic symptoms ("hypericism") have been observed in grazing animals
      ingesting large amounts of St. John's wort. In contrast, antidepressant
      medication with St. John's wort usually does not produce phototoxic symptoms.
      Recent pharmacokinetic studies suggest that the phototoxic threshold level of
      hypericin is not reached with dosages used for the oral treatment of depression.
      However, very recent reports demonstrated interactions of St. John's wort with
      other drugs such as digoxin, indinavir and cyclosporin. Blood levels of these
      drugs were dramatically decreased by St. John's wort. This should be considered
      in the treatment of skin conditions with antiviral drugs or cyclosporin.

PMID- 12063744
TI  - [Anthrenus dermatitis].
AB  - A 31-year-old male presented with widespread itchy papules, especially on the
      legs, which had appeared 4 weeks previously. He reported that his wife and both
      daughters had developed similar lesions during the last week. Numerous small
      beetle larvae had been detected in his apartment, which were identified as museum
      beetle Anthrenus museorum L. Prick test with a larva extract caused a positive
      prick-test reaction, followed by a papular delayed type hypersensitivity
      reaction. History, clinical and histological examination led to the diagnosis of
      papular Anthrenus-dermatitis. Eradication of the beetle larvae from the patient's
      apartment, followed by topical glucocorticoid therapy led to a permanent
      remission of the dermatitis in all household members.

PMID- 12063743
TI  - ["Acne and its subtypes" guideline].

PMID- 12063746
TI  - [Buruli ulcer. A mycobacterial skin disease].
AB  - Buruli ulcer is a chronic ulcerative skin disease caused by Mycobacterium
      ulcerans. It is the third most common mycobacterial disease in immunocompetent
      people and affects mainly children living in humid areas of the tropical rain
      forest. The mode of transmission is unknown. The microorganisms penetrate the
      skin via microinjuries. A few weeks after infection, a subcutaneous nodule
      develops, followed by necrosis of the subcutaneous fat and finally by a large
      dermal ulceration. Typical is the lack of an acute inflammatory response, likely
      due to an immunosuppressive toxin produced by M. ulcerans called mycolactone. The
      lesions mostly affect the limbs. Constitutional symptoms are normally absent. The
      only effective treatment consists of wide excision, often followed by skin
      grafts. Conservative measures are rarely successful. Buruli ulcer is
      characterized by low mortality and high morbidity. Early recognition and
      treatment are decisive for the complete cure and prevention of debilitating
      deformities.

PMID- 12063745
TI  - [Diagnosis of metastasis of malignant melanoma in the thyroid gland with f18-FDG
      PET scan].
AB  - Metastases in the thyroid gland are very rare. When they occur, long-term
      survival is dismal; thus an early diagnosis is critical. Malignant melanoma is
      one of the tumors which may metastasize to the thyroid gland. Therefore we wanted
      to demonstrate F18-Fluorodeoxyglucose-Positron emission tomography (F18-FDG-PET)
      is a sensitive and reliable method to identify such metastases. We report about a
      51-year-old man, who had an inguinal lymph node metastasis of a malignant
      melanoma with unknown primary tumor site. He came to us for an a follow-up F18
      FDG-PET investigation. In the PET there was a pathologic FDG-uptake in the left
      lobe of the thyroid gland. The nodule was removed and showed a malignant melanoma
      metastasis. This unusual scenario underscores the value of the PET in the
      oncologic follow-up of patients with malignant melanoma.

PMID- 12063747
TI  - [Myerson nevus as a primary patch of Gibert pityriasis rosea. A case report].
AB  - There are only few articles in literature which discuss the association between
      Meyerson's naevi and Pityriasis rosea. And when so, the discussion is done in a
      controversial way. Here an 18 year old man is presented who visits the outpatient
      clinic. He has a ten day history of a solitary Meyerson's naevus on his back.
      Over the next three weeks this naevus will develop to the typical herold patch
      followed by the classical exantheme of Pityriasis rosea. CONCLUSION: Halo
      dermatitis associated with Pityriasis rosea don't represent Meyerson's naevi. But
      they reflect the rare "nevocentric" property of a not so rare dermatose.

PMID- 12063748
TI  - [Diffuse infiltration of the external ear in a 59-year-old Brazilian patient.
      "New world" cutaneous leishmaniasis (leishmaniasis tegumentar Americana)].

PMID- 12063749
TI  - [The Rostock moulage collection].
AB  - Wax moulages are valuable witnesses of the beginning of dermatology as an
      independent speciality. In addition, they document changes in the allocation of
      clinical pictures to certain conditions. This has been due to the knowledge about
      new etiologies of dermatologic disorders, which have been steadily increasing
      since the beginning of the 20th Century. Furthermore changes in the frequency of
      certain diseases can be recognized to some extent. The still existing moulages of
      the Department of Dermatology and Venereology of Rostock offer some interesting
      examples.

PMID- 12063750
TI  - [Bullous autoimmune dermatoses. 3: Diagnosis and therapy].

PMID- 12063752
TI  - [Diagnosis and therapy of mucous membrane pemphigoid. Results of the 1st
      International Consensus Conference].

PMID- 12063751
TI  - [Comment on the contribution by Weigl CB et al. "Papillomatosis confluens et
      reticularis"].

PMID- 12063753
TI  - [Genital hemorrhage in women].

PMID- 12063754
TI  - [Malaria].

PMID- 12063755
TI  - [Asthma in adults].

PMID- 12063756
TI  - [Osteoporosis].

PMID- 12063757
TI  - [What is the French National Health Conference for?].

PMID- 12063758
TI  - [Animal models of Duchenne muscular dystrophy].

PMID- 12063760
TI  - [Classification of lymphomas].
AB  - A new classification of lymphoma has been published in 2001 under the direction
      of the World Health Organisation. This classification is based on a consensus
      between experts in haematopathology, haematology and oncology involved in
      management of lymphoma. Around 40 entities are described on the basis of
      morphology, immunophenotype, genetic and clinical presentation. Lymphomas and
      lymphoid leukaemias are gathered because tumour masses and leukaemic phases are
      present in numerous entities. This classification differentiates B-cell lymphomas
      from T/NK (natural killer) cell lymphomas. Grading the different lymphomas into
      low grade or high grade is no more required in this classification.

PMID- 12063759
TI  - [Epidemiology and etiology of non-Hodgkin's lymphoma].
AB  - Nowadays, non-hodgkin lymphoma (NHL) presents the fifth highest cancer incidence
      rate. It is one of the few cancers in which incidence has been increasing over
      the last decades in the world. Even though therapeutic progress allow a
      favourable evolution in one case out of two, NHL remains preoccupying, especially
      because of the lack of knowledge regarding its aetiology. Indeed, several factors
      have been studied and may play a concomitant role: factors linked to genetics,
      immunodepression, viruses, professional or non-professional toxics. We will
      review results from different studies evaluating the role of those factors after
      having reported current knowledge on NHL.

PMID- 12063761
TI  - [Differential diagnosis of lymphomas].
AB  - Quality of diagnosis in lymphoma is mostly conditioned by quality of initial
      biopsy. Fixed sections and immunohistochemistry are mandatory but frozen
      sections, molecular analysis and chromosomal studies are highly recommended. The
      goal of initial disease assessment is to determine prognostic factors that will
      guide treatment decision.

PMID- 12063762
TI  - [Chronic lymphoproliferative disorders].
AB  - Chronic lymphoproliferative disorders include several entities that share an
      initial indolent presentation but are considered at present not to be curable.
      Follicular lymphoma are more frequent and well characterized; therapeutic
      recommendations are adapted to prognostic factors such as stage and tumour mass.
      Marginal zone lymphoma were more recently described and include extranodal MALT
      lymphomas as well as splenic, leukemic or nodal lymphomas, each with its own
      clinical features. Lymphocytic lymphomas resemble to chronic lymphocytic leukemia
      and can be treated in the same way, while mantle cell lymphomas have a very poor
      outcome. A better definition of these entities should allow to clarify
      therapeutic recommendations before more efficient treatments become available.

PMID- 12063763
TI  - [Aggressive lymphomas].
AB  - Treatment strategies of aggressive lymphoma are the subject of this review. Main
      regimens of chemotherapy are described, as well as prognostic factors that direct
      therapeutic decisions. First-line treatment modalities of localized and advanced
      disease are envisaged, including the role of high-dose therapy with hematopoietic
      support, as well as salvage treatment of failures. Finally, the recent and major
      impact of immunotherapy based on the CD20 monoclonal antibody is outlined.

PMID- 12063764
TI  - [Lymphomas in the elderly].
AB  - About 50% of lymphomas occur in patients older than 60 and this proportion will
      probably increase in the future because of increasing lymphoma incidence and
      population ageing in developed countries. Most of the characteristics of
      lymphomas occurring in the elderly do not differ from that of their younger
      counterpart and standard treatment should be applied whenever possible. However,
      a significant proportion of these patients, which remains difficult to detect, is
      exposed to a high risk of toxicity. Further studies should lead to better
      designate this population. Among possible tools, comprehensive geriatric
      assessment can be valuable although it remains necessary to adapt it to the
      oncohematology context.

PMID- 12063765
TI  - [Monoclonal antibodies in the treatment of lymphoma].
AB  - Humanized monoclonal antibodies are dramatically improving the therapy of
      lymphomas. The anti-CD20 monoclonal antibody rituximab is active in follicular
      lymphoma, with an objective response rate varying from 48% to 73%, but also in
      others under subtypes of B lymphoma. The association of the antibody to CHOP (R
      CHOP) chemotherapy increases in diffuse large cells lymphomas by approximately
      15% complete remission rate (63% vs 76%) and survival. The rituximab allows to
      eliminate lymphoma cells of the bone marrow and it is integrated in the
      strategies of autograft. These monoclonal antibody can be coupled to radioactive
      product Iode131, Ytrium90, in view to deliver a more targeted radiotherapy.
      Remission rate is 70% with 30% of complete remission in follicular lymphomas.
      They have hematotoxicity and are more used as consolidation. Others monoclonal
      antibodies are under development and promise a great challenge for therapeutic
      studies in lymphomas.

PMID- 12063766
TI  - [Post-therapy surveillance in non-Hodgkin's lymphomas].
AB  - Post-treatment surveillance in non-Hodgkin's lymphoma is required for an early
      diagnosis of a relapse and for the detection of a potential late treatment
      related complication. The risk of relapse is highest during the first 2 years in
      aggressive lymphomas. The risk of relapse decreases then and becomes very low
      after the 5th year of follow-up. For low-grade lymphomas, the relapse rate
      remains constant for a longer period and late relapses are more common. Clinical
      examination and biological tests (blood cell count, lactate dehydrogenase and, in
      some instance, beta-2-microglobulin serum level determination) are the basis of
      the surveillance. Radiological and specific tests will be done according to the
      initial organ involvement. The frequency of the surveillance mainly depends on
      the histological subtype. Late chemotherapy-related complications include second
      cancer (solid tumor, myelodysplastic syndrome and acute leukemia), cardiac and
      endocrine toxicity. Detection of these events also requires close clinical and
      biological monitoring.

PMID- 12063767
TI  - [Health in France and the health of the French].

PMID- 12063768
TI  - [Chronic pancreatitis].

PMID- 12063769
TI  - Consideration of serum cholesterol in risk factor profiling for all young
      individuals.
AB  - AIM: To alter the adverse natural course of coronary artery disease and its risk
      factors, primary prevention should begin in childhood. DATA SYNTHESIS: High serum
      cholesterol, LDL cholesterol (LDL-C) in particular, remains the major determinant
      of atherosclerotic process beginning in childhood. Selective cholesterol
      screening of children based on family history is inadequate. Tracking of
      childhood elevated cholesterol in conjunction with other risk factors into
      adulthood argues in favor of universal screening in the young. Further,
      individual adverse levels of LDL-C not only increase the incidence of adulthood
      dyslipidemia, but also markedly enhances the prevalence of obesity and
      hypertension seen in the adult population. CONCLUSIONS: Screening of all young
      individuals for serum cholesterol along with a cardiovascular risk factor profile
      is recommended. Cardiovascular disease remains a public health issue and
      identifying young individuals at risk is basic to prevention.

PMID- 12063770
TI  - Non-invasive vascular detection of early signs of atherosclerosis in
      hypercholesterolemic children: why and how.
AB  - Atherosclerosis is a lifelong disease process that begins in childhood and may
      lead to cardiovascular disease in middle age or later. Non-invasive methods for
      vascular diagnosis help identify hypercholesterolemic children to treat with
      dietary or pharmacological intervention on the basis of anatomical or functional
      markers of arterial pathology. It would be unethical to assess these markers
      using angiographic or other invasive procedures (such as intravascular
      ultrasound), but the measurement of intermediate vascular end-points using non
      invasive techniques is feasible. We here review the methods and procedures of non
      invasive vascular examination that have been demonstrated to be feasible and
      informative with regard to arterial pathology in hypercholesterolemic children.
      These include measuring carotid intima-media thickness (IMT) by means of B-mode
      imaging, Doppler evaluation of the transvalvular aortic pressure gradient,
      measuring coronary calcium by means of computed tomography, studying the elastic
      properties of arteries, detecting impaired vasodilation, and measuring arterial
      remodelling. Suggested operative guidelines could be to measure carotid IMT in
      all hypercholesterolemic children aged > 10 years. The measurement should be
      repeated each year if the IMT is in the upper tertile of distribution for that
      age. A progression in IMT or the development of new lesions during the study
      could be an indication for more aggressive treatment.

PMID- 12063771
TI  - Lipoproteins and atherosclerosis in children: an early marriage?
AB  - AIM: Describe the relationship between serum lipoproteins and the development of
      atherosclerosis in young subjects aged 15-34 years, and discuss the implications
      for prevention of coronary heart disease. DATA SYNTHESIS: Data from gross and
      microscopic evaluation of aorta and coronary arterial specimens as part of the
      Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study
      demonstrates that by the age of 15 years, all subjects have atherosclerosis.
      Lipoprotein risk factors for coronary heart disease are associated with the
      extent and prevalence of gross aortic and coronary atherosclerosis and with the
      development of microscopic coronary plaques that have qualities consistent with
      clinically significant lesions. Association of lipoprotein risk factors with
      intermediate type atherosclerotic lesions becomes evident in subjects in their
      late teens, whereas associations with raised lesions become evident in subjects
      greater than 25 years of age, consistent with a transitional role of intermediate
      lesion in the formation of advanced plaques. CONCLUSIONS: Atherosclerosis begins
      in childhood and a significant number of young people have advanced coronary
      artery plaques. Early atherosclerosis is accelerated by lipoprotein risk factors.
      Thus, long-range prevention of atherosclerosis should begin in childhood and
      should include measures to control hyperlipidemia.

PMID- 12063772
TI  - Statins in children. Why and when.
AB  - There is now ample evidence to demonstrate that atherosclerosis begins in
      childhood and is significantly accelerated in certain genetic disorders, most
      notably familial hypercholesterolemia (FH). Untreated FH, both the homozygous and
      heterozygous forms, carry a substantial burden of morbidity and mortality if left
      untreated or inadequately treated. Males with FH are at earlier and greater risk
      than females and thus should begin therapy earlier, preferably at about 10. While
      bile acid sequestrants have long been considered the drug of choice in children,
      they have never been approved for pediatric use by FDA, are poorly tolerated,
      marginally effective at lowering low-density lipoprotein cholesterol and have
      minimal well controlled studies in children upon which to adequately assess
      safety. Over the last decade statins have been studied extensively in children
      and adolescents, although many of these studies have also been poorly controlled,
      of short duration, too small and lack detailed assessment. However there has been
      at least one large, randomized, placebo-controlled and comprehensive study with
      lovastatin in adolescent males that indicated efficacy similar to that
      anticipated in adults and no apparent safety concerns. While additional well
      controlled studies are needed, especially those focusing on surrogates of
      atherosclerosis to determine clinical benefit, it is opportune for re-evaluation
      of current treatment guidelines.

PMID- 12063773
TI  - Safety and efficacy of treatment of children and adolescents with elevated low
      density lipoprotein levels with a step two diet or with lovastatin.
AB  - BACKGROUND AND AIM: The risk factor precursors of arteriosclerotic cardiovascular
      disease (ASCVD) are expressed in children and adolescents and development of
      coronary atherosclerosis in adulthood. Certain pediatric subjects have inherited
      disorders such as familial hypercholesterolemia (FH), familial combined
      hyperlipidemia, hyperapobetalipoproteinemia, and the metabolic syndrome, which
      often lead to more marked elevations in plasma low-density lipoprotein (LDL)
      levels, placing them at increased risk of premature ASCVD. The aim of this report
      was to examine available data on the safety and efficacy of treatment of children
      and adolescents with elevated LDL-cholesterol (LDL-C). DATA SYNTHESIS: Treatment
      of adolescents with elevated LDL-C levels of 130 mg/dL, randomized to an
      intervention group receiving a stricter Step Two diet, produced a significantly
      greater fall in LDL-C than those randomized to the usual care group after three
      years of follow-up in the Dietary Intervention Study in Children (DISC).
      CONCLUSIONS: There were no differences between the intervention and usual care
      groups in growth and development after either 3 or 7 years of follow-up. In the
      Lovastatin in Adolescent Males Study (LAMS), 132 boys aged 10 to 17 years with
      heterozygous FH were randomized into a placebo group or a group receiving up to
      40 mg/day of lovastatin. The treatment group had up to a 27% reduction in LDL-C,
      compared with the placebo group and there were no differences in growth, sexual
      maturation, hormone or biochemical levels. Longer-term studies are required to
      assess further the safety of such treatments, and whether treatment will delay
      the early expression of atherosclerosis such as intima media thickness and
      endothelial dysfunction.

PMID- 12063774
TI  - Global cardiovascular risk in children and their families: the Prevention
      Education Program (PEP), Nurnberg.
AB  - BACKGROUND AND AIM: The Prevention Education Program (PEP) is a 14-year
      prospective study designed to identify and evaluate cardiovascular risk factors
      in school-children and their families. The second aim of the PEP is to test the
      hypothesis that the individual risk can be changed by family lifestyle
      modifications. METHODS AND RESULTS: We here report on the evaluation of the
      global cardiovascular risk constellation in 3283 adults and 3220 children and
      adolescents (aged up to 16 years): 36% of the children were passive smokers and
      35% of the adults were smokers. The prevalence of low-density lipoprotein
      hypercholesterolemia was nearly identical in the children (> or = 130 mg/dL) and
      adults (> or = 155 mg/dL), being respectively 17% and 18%. Low high-density
      lipoprotein-cholesterol concentrations (< or = 35 mg/dL) were recorded in 4% of
      the adults and 2% of the children. The prevalence of hypertriglyceridemia was 6%
      in adults (> or = 200 mg/dL) and 5% in children (> or = 130 mg/dL). Nine percent
      of the adults were obese (body mass index > 30 kg/m2) and 6% of the children (>
      20% ref. weight). High blood pressure was found in 16% of the adults and 17% of
      the children. CONCLUSIONS: Because of the high prevalence of risk factors in
      childhood, primary prevention of cardiovascular diseases should start as soon as
      children start school.

PMID- 12063775
TI  - Gene therapy for familial hypercholesterolemia.
AB  - Current approaches to the treatment of homozygous familial hypercholesterolemia
      (FH) are not optimal and this disorder remains an excellent candidate for the
      development of clinical gene therapy. Preclinical proof of principle studies of
      long-term expression of both the low density lipoprotein (LDL) receptor and the
      very low density lipoprotein (VLDL) receptor in relevant animal models of
      homozygous FH demonstrating reduction in both LDL cholesterol and atherosclerosis
      have been performed. The major rate-limiting step in the development of clinical
      trials is the development of safe vectors that provide long term expression. Once
      these vectors are available, effective clinical gene therapy for homozygous FH is
      likely to become a clinical reality.

PMID- 12063776
TI  - Implications of the human genome project for the identification of genetic risk
      of coronary heart disease and its prevention in children.
AB  - Most male citizens of Western countries already have some degree of
      atherosclerosis by the age of 18, indicating that initiation of atherosclerosis
      in childhood is a virtually ubiquitous process. This process has a strong genetic
      component. However, identifying the exact nature of that component is not an easy
      task, because in the overwhelming majority of cases atherosclerosis is due not to
      disorders in single genes but to the effects of many genes operating together
      against a variable environmental background. The preliminary results of the
      sequencing of the human genome indicate fewer genes, but more complexity in the
      regulation of the expression of these genes, than was previously thought. For
      these reasons it is likely that prediction and management of atherosclerotic risk
      in children in the next years will depend not on the results of genetic testing,
      but on the differentiated analysis of classical risk factors. These issues are
      discussed in detail in this review.

PMID- 12063778
TI  - Eating behaviour, body mass index and lipids of children in a free-living rural
      Sicilian population.
AB  - BACKGROUND AND AIM: The preliminary findings of an epidemiological study
      conducted in 1989 in Ventimiglia di Sicilia (a rural village in the hilly
      hinterland 50 km from Palermo) described a population mainly made up of farmers,
      which had a very low incidence of early cardiovascular mortality, lower total
      cholesterol plasma concentration than the Italian average, and nutritional habits
      following the criteria of the Southern Italian Mediterranean diet. Since a high
      prevalence of body weight abnormalities was found in this population and an 11
      year follow-up revealed that both body weight and fat distribution were
      significantly associated with total and cardiovascular mortality, we studied the
      eating behaviour, body weight and lipid levels of 249 school-children living in
      the village. The aim of the study was to verify whether the children showed
      similar body weight abnormalities and quantitative dietary excesses as the adults
      of the same families. METHODS AND RESULTS: The dietary habits of 97 children
      (about one third of the study population) had a higher total caloric,
      monounsaturated fatty acid and fibre intake, and a lower saturated fatty acid and
      cholesterol intake, than an all-Italy sample of school-children. The lipid
      profile of this group of very young subjects was fairly good, but 13% had LDL
      cholesterol levels of more than 130 mg/dL and 11% had HDL-cholesterol levels of
      less than 35 mg/dL. About 28% were considered to be above the 95th percentile of
      body weight and this was associated with a higher daily total caloric intake.
      CONCLUSIONS: Because obesity is associated with a high total caloric intake and
      various other risk factors even in young children, it is possible that a
      successful prevention campaign including behavioural education in schools could
      reduce the incidence of cardiovascular disease at older ages.

PMID- 12063777
TI  - Lp(a), homocysteine and a family history of early ischemic cerebral stroke.
AB  - BACKGROUND AND AIM: High plasma lipoprotein(a) [Lp(a)] and homocysteine (HCY)
      levels are now considered to be independent risk factors for cerebro- and
      cardiovascular atherosclerotic occlusive disease, but little is known about the
      influence of Lp(a) and HCY on the early events of ischemic disease or their
      significance in subjects with a positive family history of ischemia. The aim of
      this study was to evaluate the relationship between HCY levels and the severity
      of ischemic cerebral stroke, and investigate whether there was a correlation
      between Lp(a) and HCY levels in the stroke patients and their children. METHODS:
      The study involved 35 patients with early ischemic cerebral stroke aged 46.1 +/-
      6.6 years and their 50 children aged 17.2 +/- 5.5 years. The patients were
      grouped on the basis of the form of the stroke (transient, progressive or
      complete stroke), and their levels of Lp(a), HCY, uric acid (UA), fibrinogen (Fb)
      and factor VII (FVII) activity were measured. RESULTS: HCY and Lp(a)
      concentrations increased with the severity of the ischemia, being highest in the
      patients with complete stroke (15.1 +/- 2.9 mumol/L and 32.9 +/- 37.6 mg/dL
      respectively). A similar trend was found in the offspring, with the highest HCY
      and Lp(a) values in the children of complete stroke patients (12.6 +/- 4.4
      mumol/L and 23.0 +/- 24.6 mg/dL). The control values were respectively 8.7 +/-
      1.6 mumol/L and 5.35 +/- 7.05 mg/dL. The following correlations between the
      parents and children were noted: Lp(a) (r = 0.87 p < 0.0001), UA (r = 0.71 p <
      0.001), HCY (r = 0.45 p < 0.05), FVII (r = 0.45 p < 0.05), and Fb (r = 0.42 p =
      0.06). Correlations between Lp(a) and HCY (r = 0.47 p < 0.05) and Fb and FVII (r
      = 0.60 p < 0.01) were found in the children. Multiple regression analysis
      revealed that only Lp(a) and Fb significantly influenced HCY levels in the
      offspring with a positive family history. CONCLUSIONS: HCY levels correlate with
      the severity of ischemic cerebral stroke and, in families with a history of
      ischemic cerebral stroke, the levels of the risk factors in children are
      determined by the levels in their parents.

PMID- 12063779
TI  - Stratification of risk in children with familial hypercholesterolemia with focus
      on psychosocial issues.
AB  - AIM: This paper discusses the clinical implications of making a diagnosis of
      familial hypercholesterolemia (FH) in children and data on psychosocial issues.
      DATA SUMMARY: The case for treating FH in children is based on pathophysiological
      considerations. Some authors claim that treatment may be harmful, partly because
      the psychosocial risks have not been assessed. The available data indicate that
      psychological distress does not seem to be a problem in testing and treating most
      children for FH, although a few may develop social and emotional problems,
      experience family conflicts, or have problems with the diet or bile acid binding
      resins. CONCLUSIONS: Parental preferences and the psychosocial function of the
      child should be considered and a complete assessment should be made of the
      potential risk of coronary heart disease (CHD) on the basis of established CHD
      risk factors. Boys and girls with total cholesterol concentrations of > 7.0
      mmol/L and a family history of early CHD (first or second degree relatives with
      CHD, in males before the age of 40 and in females before the age of 50 years),
      and boys with cholesterol concentrations of > 10.0 mmol/L regardless of family
      history, should be considered at high risk and start dietary treatment as early
      as possible (preferable before the age of ten years). Girls at high risk may
      start statins by the age of 18 years, whereas starting statins should be
      considered in boys between the ages of 10 and 18 years. Children with FH at low
      to moderate risk of CHD may wait until adulthood or start treatment depending on
      an individualized evaluation.

PMID- 12063780
TI  - [Scientific problems and tasks of medical monitoring].
AB  - Medical monitoring is regarded as a task of detecting and classifying human
      abnormalities. A computer medical monitor (CMM) is a complex hierarchical system
      with artificial intellect elements at the top levels of hierarchy. Each level of
      hierarchy performs a definite task in collecting and processing current
      information. Based on this approach, the authors put forward tasks of medical
      diagnostic and prognostic studies by developing the hierarchical network
      architecture of CMM.

PMID- 12063781
TI  - [Calculation of impact blood volume by a rheogram].
AB  - The approximated analytical expression for calculation of impact blood volume by
      using some parameters of a rheogram is derived on the basis of the authors'
      simple model of an elastic vessel having blood. The formula proposed to measure
      impact blood volume contains no empirical adjustable parameters is given.

PMID- 12063783
TI  - [Effect of the shape of the pump segment cavity of the perfusion line on
      perfusate consumption].
AB  - The paper provides strong evidence for the need for the perfusion artery of
      circular inner section to be preserved by a pump segment during both storage and
      use of articles. A change in the shape is shown to cause a substantial reduction
      in perfusate consumption. The limit of allowable error of the shape of the inner
      section of arteries is given.

PMID- 12063782
TI  - [Measuring and decoding the capabilities of digital radiographic images].
AB  - The paper deals with the theory and practice of digital X-ray diagnosis. The
      adverse factors of formation of a digital X-ray film are considered. They
      included geometric and dynamic blurrinesses, blurriness of an image receiver, and
      the contrast and dynamic range of digital image. Analysis of a great deal of
      clinical data shows the capacities of digital X-ray study to diagnose different
      forms of pulmonary tuberculosis and other thoracic diseases.

PMID- 12063784
TI  - [Assessment of the quality of formalized medical documents].
AB  - The paper deals with the informational approach to assessing the quality of
      formalized medical documents. It shows it possible to apply the above approach to
      analyzing the components of medical support of automatic diagnostic systems.

PMID- 12063785
TI  - [Experimental study of the hydrodynamics of modern artificial heart valves].
AB  - The paper presents the results of experimental studies of the hydrodynamics of
      currently available artificial cardiac valves (ACV). Photo chromatographic
      visualization was used to study the hydrodynamics of ACV. The hydrodynamic
      characteristics of a MIX discal valve (Russia) and a St. Jude two-leaflet one
      (USA), which have been clinically applied for more than 15 years, are presented.

PMID- 12063786
TI  - [Approximate methods for calculating the probability of radiation complications.
      The PKLQ method].
AB  - A method of approximate calculation of the probability of resorption of a lesion
      focus by means of three mathematical models: the Poisson model, the Klepper
      model, and the LQ-model (the PKLQ method) is described. The method is based on a
      procedure for reducing SOD to the preset scope of a lesion focus. It is suggested
      that radio-sensitive (RS) cells predominate in the focus of lesion; radio
      resistant cells are available in small quantities or their radiobiological
      properties differ from RS cells.

PMID- 12063787
TI  - [Analysis of the effects of low doses of ionizing radiation].
AB  - The paper analyzes the data available in the literature and the authors' own
      findings relating to the effects of low-dose ionizing radiation on biological
      objects, which confirm a higher likelihood of general somatic diseases upon
      exposure to small dosages (as low as 200 meq).

PMID- 12063788
TI  - [Microcontroller temperature regulator MPT110 for drying-sterilizing cabinets].
AB  - The paper describes a MPT-110 temperature microcontroller developed by the closed
      joint-stock company "OPLEKS" (Orel, Russia) and the results of comparative tests
      performed in the @IIICC-80 drying sterilizing cabinet. The use of the MPT-110
      controller is shown to improve the quality of control and to shorten the times
      that is taken for the cabinet to reach the preset temperature point.

PMID- 12063789
TI  - [A set of components for endothoracic surgery].
AB  - The paper considers a universal set of hardware components for endothoracic
      surgery. A composition of the set is defined. The introduction of the set into
      clinical practice is shown to be significantly convenient for an operating team
      and to yield a higher level of medical aid.

PMID- 12063790
TI  - [Interpreting medical devices].
AB  - The specific properties of softwares for interpretation of physiological signals
      are discussed. Problems in the presentation of inaccurate knowledge and in the
      assessment of the quality of software realization of this knowledge are
      identified. Ways of describing inaccuracies by using the factors of certainty,
      inaccurate logic, linguistic approximations, and three-value logic are
      considered. Using the well-known approaches to testing the ECG and external
      respiration analyzing systems as examples, the authors show it necessary to
      develop special methods to evaluate the efficiency, selectivity, and stability of
      inferences for slight-magnitude conclusions.

PMID- 12063791
TI  - [Use of computer software for indirect molecular genetic identification of
      unidentified bodies].
AB  - The authors discuss the development and use of computer software for realization
      of indirect DNA identification, based on identification of biological relation.
      Estimated algorithms of this method are based on regularities of parental signs
      inheritance by children and consist in comparative analysis of allele states of
      nuclear DNA typed locuses in unidentified bodies and probable parents of these
      dead subjects and subsequent estimation of the coefficients of the likelihood of
      hypotheses of their probable blood relationship. Available software maintain the
      database with identification characteristics of VNTR and STR locuses, HLA DQA1
      locuses, and PM system (potential set of 23 locuses). The results of
      identification are presented as lists of exclusions and tables with estimated
      likelihood coefficients for the probability expert evaluation of relationship.
      The suggested computer-aided method of indirect identification is a new highly
      effective tool for personality identification by chromosome markers under
      conditions of mass information processing in examinations of unidentified
      corpses.

PMID- 12063792
TI  - [Age-specific changes in bone tissue microstructure and potential for use for
      human identification].
AB  - The possibility of using the data of quantitative microscopy of bone tissue for
      evaluation of age with the aim of personality identification is discussed.
      Computer histomorphological analysis of third rib, tibial lower epiphysis and
      diaphysis fragments from 564 male corpses of known age (0-90 years) was carried
      out. A complex of parameters most strongly correlating with age was detected:
      extension of active osteogenesis zone in the longitudinal section of a rib,
      thickness of layers of internal and external general diaphyseal laminae in the
      tibial bone, trabecular area in the tibial epiphyseal preparation, etc. Age
      specific changes in bone tissue structures is characterized by a great variety
      and depends on the type and location of these structures. Bone tissue
      characteristics change irregularly and asynchronously, therefore their
      correlations with age are different in different age groups. A general biological
      interpretation of the results is offered.

PMID- 12063793
TI  - [Study of the skeleton of Admiral F. F. Ushakov].
AB  - Reports the results of examination of the skeleton of Admiral F. F. Ushakov,
      carried out in connection with canonization in the Russian Orthodox Church.
      Heretofore unknown data on the somatic characteristics of F. F. Ushakov and his
      diseases are presented. Special attention is paid to uneven age involution of the
      skeleton and the hypoergic aging velocity. A detailed morphological similarity
      between the skulls of F. F. Ushakov and monk Feodor (Admiral's uncle, I. I.
      Ushakov) evidenced common features inherited through the masculine line. Modern
      computer technologies showed that the appearance of F. F. Ushakov, determined by
      the skull and postcranial skeleton, agree with his appearance on the life-time
      portrait, in spite of Professor M. M. Gerasimov's opinion (1949). In this
      connection, the possibility of repeated reconstruction of Admiral Ushakov's
      appearance is proven.

PMID- 12063794
TI  - [Serological detection of Rhesus antigen D in blood traces from Rh-negative (cde)
      people].
AB  - A D-like structure was serologically detected on the internal side of Rh-negative
      (cde) erythrocyte membrane. This structure is absolutely inaccessible for anti-D
      antibodies in morphologically intact liquid blood erythrocytes. In hemolyzed
      erythrocytes of blood stains this antigenic structure, serologically identified
      as Rh antigen D, is accessible for binding with anti-D antibodies and for
      detection by the absorption-elution test, particularly so after blood stain
      treatment with proteases.

PMID- 12063795
TI  - [Population study of HLA DQA1, LDLR, GYPA, HBGG, D7S8, and GC loci in Caucasians
      living in the Ural region of Russia].
AB  - Allele frequencies have been determined for 6 tested locuses. The distribution of
      HLA DQA1 gene and locuses of Polymarker kit (Perkin Elmer, USA) for population
      studies conformed to the Hardy-Weinberg equilibrium (HWE). Inequilibrium for
      linkage for all possible locus pairs was tested by an accurate test. No
      statistically significant inequilibrium was detected. Paired comparison of allele
      frequencies of tested locuses of the Ural population with other Caucasoid
      populations showed homogeneity for GYPA, HBGG, D7S8, and HLA DQA1 locuses.
      Significant differences for 1 and 2 of the 4 compared pairs were detected for
      LDLR and GC locuses, respectively. The total discrimination potential for 6
      tested locuses was 0.9995. Our population study showed that high informative
      value of the tested genetic markers and conformity to HWE make them a useful tool
      for forensic genetic studies in the Ural Caucasoid population. Preliminary
      assessment of the efficiency of PCR of 6 studied locuses by capillary
      electrophoresis is highly effective in typing of DNA samples isolated from
      material evidences with negligible content of biological material with presumably
      high degree of degradation and for evaluating the positive and negative
      amplification controls.

PMID- 12063796
TI  - [Analysis of mortality caused by ischemic heart disease in Astrakhan from 1983 to
      1997].
AB  - Mortality caused by coronary disease is analyzed for Astrakhan for the period of
      1983-1997 (total, non-hospital and hospital mortality). The distribution of
      mortality by the years and months of the year, sex, age, and cause of death
      structure is analyzed as exemplified by 6505 deaths.

PMID- 12063798
TI  - [Brain acetaldehyde and ethanol: method of determination and diagnostic
      significance in ethanol poisoning].
AB  - The content of ethanol and acetaldehyde in the limbic cortex and reticular
      formation of the brain was measured by gas-liquid chromatography in lethal
      ethanol poisoning. The content of acetaldehyde was significantly increased in the
      gyrus cinguli of the brain. Lethal poisonings occurred during any stage of
      ethanol intoxication. The data characterizing individual ethanol tolerance were
      obtained, which can be used for differential diagnosis of ethanol poisoning in
      practical forensic medicine.

PMID- 12063797
TI  - [Opiate poisoning (an analysis of section material)].
AB  - Section specimens from subjects dead from narcotic poisoning in 1998-1999 are
      analyzed. The results indicate that narcotic poisonings were primarily due to
      opiates or their combinations with other drugs (primarily ethanol). The ratio of
      male to female mortality was 3:1. Death after narcotic poisoning occurs at home
      in the majority of cases. The concentration of morphine/heroin in the blood and
      urine of victims varied within a very wide range. Acute renal failure,
      myoglobulinuremic nephrosis, and compression syndrome are not typical of acute
      narcotic poisoning. Use of immunotest for urinary morphine-heroin deserves
      further investigation.

PMID- 12063799
TI  - [Sample preparation in analysis of synthetic pyrethroids on biological objects].

PMID- 12063800
TI  - [Legal bases for physician activity in modern socioeconomic conditions (VIII
      Russian National Congress "Man and Medicines")].

PMID- 12063801
TI  - [Modified variant of macroscopic study of the myocardium in cases of sudden death
      from cardiovascular diseases].
AB  - A method for examination of the myocardium modified for forensic medical expert
      evaluations is described. The number of incisions made to open the heart cavities
      is decreased. The incisions for examining the myocardium are made at an angle of
      45 degrees to the axis of the heart, which is simpler, allows the restoration of
      the organ shape, and permits the examination of a larger area of sections for
      detecting the slightest changes in the myocardium.

PMID- 12063802
TI  - [Significance of histochemical parameters of erythrocyte catalase activity for
      diagnosing mild concussion and contusion of the brain].
AB  - A total of 227 primary and repeated forensic medical expert conclusions in
      victims with slight craniocerebral injuries (CCI) are analyzed. Erythrocyte
      catalase (CTer) activity was analyzed on the basis of the results of computer
      quantitative morphometry of histochemical analysis of blood smears from 50
      victims with slight CCI. CTer activity correlated with the severity of CCI. A new
      objective method for histochemical diagnosis of slight concussion and contusion
      of the brain is suggested, which rules out errors in forensic medical expert
      evaluations in examinations of this category of victims.

PMID- 12063803
TI  - Percutaneous retrieval of a Wallstent from the pulmonary artery following stent
      migration from the iliac vein.
AB  - Wallstents are being used increasingly in conjunction with balloon dilatation for
      treatment of iliac vein stenosis. Stent misplacement or migration is a
      complication of the procedure, and may be symptomatic and warrant repositioning
      or removal. We report the case of a patient whose iliac vein stenosis was managed
      with two overlapping Wallstents and was complicated by embolization of one stent
      into the right ventricle (RV) and the other to the pulmonary artery (PA). This
      article illustrates percutaneous endovascular removal of a migrated stent from
      the PA using a jugular and femoral approach.

PMID- 12063804
TI  - Iatrogenic forearm compartment syndrome in a cardiac intensive care unit induced
      by brachial artery puncture and acute anticoagulation.
AB  - A previously healthy patient developed late compartment syndrome in the cardiac
      intensive care unit after a brachial artery puncture due to acute heparinization
      after successful percutaneous transluminal coronary angioplasty (PTCA) and stent
      implantation. The cardiologists recognized the problem and immediately consulted
      an orthopedic surgeon, who promptly performed surgery. The latter consisted of
      decompression and fasciotomy. The patient recovered excellent hand function
      without any neurologic or muscular deficits. Knowledge and understanding of the
      clinical aspects of this complication are crucial in this devastating syndrome.

PMID- 12063805
TI  - Antiplatelet therapy and coronary interventions: childhood friends or permanent
      partners?

PMID- 12063806
TI  - Cost efficacy of platelet glycoprotein IIb/IIIa antagonists in clinical trials
      and clinical practice.

PMID- 12063807
TI  - Experience with glycoprotein IIb/IIIa antagonists in patients with acute coronary
      syndromes.

PMID- 12063808
TI  - Glycoprotein IIb/IIIa antagonism and fibrinolytic therapy for acute myocardial
      infarction.
AB  - Fibrinolytic therapy for the treatment of ST-segment elevation myocardial
      infarction unquestionably reduces mortality when administered within 12 hours of
      symptom onset. By promptly restoring antegrade perfusion, infarct size is
      limited, ventricular function is less compromised, and mortality rates are
      lowered. Although fibrinolytic therapy initially restores antegrade flow in the
      infarct vessel in the majority of patients, sustained, tissue-level reperfusion
      occurs in only approximately one fourth of patients. Thrombin and platelets
      associated with a coronary thrombus are not specifically targeted by fibrinolytic
      agents, but rather have paradoxically increased activity. These components
      contribute to the tendency for vessel reocclusion after initially successful
      reperfusion. Thus, adjunctive therapy with antithrombins and antiplatelet agents
      are essential in the successful treatment of a coronary thrombus. Although
      aspirin has been shown to reduce mortality in acute myocardial infarction, it is
      a weak antiplatelet agent that is pathway specific. Glycoprotein IIb/IIIa
      inhibitors are potent antiplatelet agents that block the final common pathway for
      platelet aggregation. Thus, the growing evidence of platelet preeminence in the
      pathophysiology of failed thrombolysis has lead to the study of combination drug
      therapy with glycoprotein IIb/IIIa inhibition and reduced dose fibrinolytic
      agents in the treatment of acute ST-segment elevation myocardial infarction. This
      article reviews the rationale, results, and clinical implications of the major
      trials of combination drug therapy in acute myocardial infarction.

PMID- 12063809
TI  - Direct thrombin inhibitors for percutaneous coronary intervention in the current
      era of platelet glycoprotein IIb/IIIa inhibition.

PMID- 12063810
TI  - Low molecular weight heparins and glycoprotein IIb/IIIa antagonists.
AB  - The consistent message that emerges from virtually every recent acute coronary
      syndrome (ACS) trial is that the old "standard" of using aspirin and
      unfractionated heparin (UFH) can be considerably improved upon. Low molecular
      weight heparins (LMWHs) (most notably enoxaparin) are emerging as a broad
      replacement for UFH. Initial safety concerns about combining LMWHs and
      glycoprotein (GP) IIb/IIIa antagonists have not been borne out; in fact, major
      bleeding complications may be lower with LMWHs. Clinical outcomes to date suggest
      that LMWHs may be a better first line therapy than UFH on which to superimpose
      adjunctive GP IIb/IIIa antagonists. Emerging clinical experience further supports
      the safety and efficacy of this combination regimen. The forthcoming SYNERGY
      study will prospectively compare enoxaparin and UFH in high risk patients in whom
      an invasive management strategy is pursued, with a high coincident use of GP
      IIb/IIIa antagonists. As the standard of care moves forward, we will see
      increasing use of LMWHs, with and without GP IIb/IIIa antagonists in
      conservatively and invasively managed patients.

PMID- 12063811
TI  - Glycoprotein IIb/IIIa antagonists in the setting of rescue percutaneous coronary
      intervention.
AB  - It is clear that survival and better outcomes after acute myocardial infarction
      (AMI) are dependent on rapid, complete, and sustained reperfusion of the affected
      myocardium. Thrombolytic therapy is currently the most common reperfusion
      strategy in AMI, however, a significant proportion of patients fail to reach
      reperfusion with this form of therapy. There is evidence from randomized trials
      that rescue percutaneous coronary intervention (PCI) for failed thrombolysis may
      convey better outcomes to patients when compared to a conservative management.
      Nevertheless, it is not surprising that in this inherently thrombogenic milieu,
      rescue PCI has a lower success rate and a high incidence of rethrombosis, which
      have a profoundly negative impact on the outcome of patients. Platelets are
      thought to play a central role in the pathophysiology of failed thrombolysis and
      in the thrombotic complications following PCIs. Therefore, platelet glycoprotein
      (GP) IIb/IIIa antagonist may be of benefit in the setting of rescue PCI. Two
      retrospective subgroup analyses have suggested that these potent antiplatelet
      agents may improve the outcome of patients undergoing rescue PCI after failed
      full-dose thrombolytic therapy. An increase in major bleeding, however, has also
      been noted. Therefore, in light of the lack of evidence deriving from randomized,
      placebo-controlled trials, careful consideration of several aspects relevant to
      this setting is needed before GP IIb/IIIa antagonists are administered in rescue
      percutaneous coronary procedures.

PMID- 12063812
TI  - Vascular access.

PMID- 12063813
TI  - Outcomes studies and the biomedical research enterprise.

PMID- 12063814
TI  - Device implantation and anticoagulation.

PMID- 12063815
TI  - Medicare and your practice: an update.

PMID- 12063816
TI  - Posttraumatic stress disorder in primary care. Part 1: Recognition and diagnosis.

PMID- 12063817
TI  - A practical approach to diagnosing scrotal masses.

PMID- 12063818
TI  - Does Chlamydia pneumoniae have a role in atherosclerosis?

PMID- 12063819
TI  - Saw palmetto for BPH: a review of a meta-analysis.

PMID- 12063820
TI  - Taking care of the second tier.

PMID- 12063821
TI  - Epidemiologic and etiologic factors of pancreatic cancer.
AB  - Ranking fourth as a cause of death from cancer for men and women in the United
      States, pancreatic cancer represents a significant challenge for physicians and
      surgeons. In addition to the elderly, high-risk groups include blacks, men,
      smokers, and patients with certain preexisting diseases such as pancreatitis and
      long-standing diabetes. Various inherited genetic disorders cause approximately
      5% to 10% of the total cases of pancreatic cancer. Smoking doubles the risk of
      pancreatic cancer. Control of smoking offers the best available strategy for
      reducing the incidence of this disease. Dietary measures to reduce the risk of
      pancreatic cancer include maintenance of normal body weight and consumption of a
      well balanced diet with adequate amounts of fruits and vegetables. Chronic
      pancreatitis caused by heavy alcohol consumption or, rarely, by an underlying
      inherited disorder is another strong risk factor, but because this benign disease
      is uncommon, elimination of this underlying cause would have minimal impact on
      the frequency of pancreatic cancer.

PMID- 12063822
TI  - Supportive care for patients with pancreatic adenocarcinoma: symptom control and
      nutrition.
AB  - Pancreatic cancer is most frequently a fatal disease with many associated
      morbidities. Clinicians skilled in its treatment are adept at management of
      symptoms caused by local and systemic effects of the malignancy. Patients should
      be assured that there are many treatments that can be used aggressively to
      maintain their comfort and independence for as long as possible. Patients should
      be encouraged to inform their health care providers of any discomfort or medical
      or psychological problems they are experiencing. At times, referrals to
      specialists can be beneficial for consideration of specific symptom-improving
      interventions. Timely referral to a palliative medicine service and hospice can
      have significant beneficial impact on the total care of the patient and on home
      caregiver.

PMID- 12063823
TI  - A comprehensive update on the use of chemotherapy for metastatic pancreatic
      adenocarcinoma.
AB  - Phase II trials of combination chemotherapies have shown encouraging palliative
      benefit, objective response rates, and survival outcomes. Until ongoing phase III
      trials confirm these benefits, the current standard treatment for metastatic
      pancreatic adenocarcinoma remains single agent gemcitabine. The fixed rate
      infusion schedule of 10 mg/m2/min is gaining wide acceptance and is a promising
      investigational priority. A very reasonable alternative to single agent
      gemcitabine, and our bias, is enrollment into clinical trials evaluating novel
      gemcitabine-based combinations. Further investigation is needed to determine
      optimal incorporation of so-called targeted therapy with combination
      chemotherapy.

PMID- 12063824
TI  - Exploiting molecular targets in pancreatic cancer.
AB  - Oncology has entered an era of molecular therapy. Given the multitude of
      molecular defects involved with pancreatic carcinogenesis, invasion, and
      metastasis, it is unlikely that single-agent targeted therapy will alter the
      course of this disease. Given the emergence of molecular targets and a growing
      number of agents available for clinical development, however, meaningful
      improvements in patient outcomes are expected, particularly if treatments are
      designed and delivered rationally.

PMID- 12063825
TI  - Immunotherapy for pancreatic cancer: current concepts.
AB  - Despite advances in chemotherapy and surgical technique, patients with pancreatic
      cancer often succumb to local recurrence or metastatic spread. The need for new
      therapeutic strategies for this disease coupled with a better understanding of
      basic immunology have led to the development of novel anti-tumor vaccines. This
      review focuses on the historical development of tumor vaccines emphasizing the
      identification of potential pancreatic tumor antigens. The role of both B-cell
      and T-cell responses in tumor rejection will be reviewed. Methods for antigen
      presentation, including peptides, recombinant viral and bacterial vectors,
      dendritic cells, and whole cell approaches will be discussed. The use of immune
      adjuvants and improved methods of vaccine delivery will also be explored. The
      full potential for the immunotherapy of pancreatic cancer awaits the results of
      early phase clinical trials. The development of pancreatic cancer vaccines
      represents a useful paradigm for the translation of basic research into the
      clinical arena.

PMID- 12063826
TI  - Molecular pathogenesis of pancreatic cancer.
AB  - Our understanding of the biology of pancreatic carcinoma has greatly benefited
      from studies of the genetic alterations in this tumor type. The p16-CDK4-cyclinD
      Rb pathway, the p53 tumor suppressor pathway, and the DPC4/Smad4 pathway are
      genetically inactivated in the majority of sporadic pancreatic carcinomas,
      whereas oncogenic K-ras signaling is almost ubiquitously activated. These genetic
      data have provided the basis to shape a first genetic progression model of this
      tumor type. Furthermore, a number of well defined genetic syndromes which are
      associated with an inherited risk for pancreatic carcinoma have been identified
      recently.

PMID- 12063827
TI  - Regional chemotherapy.
AB  - Regional chemotherapy is an interesting treatment option in patients with
      advanced pancreatic cancer but cannot be considered standard treatment, and it
      should not be performed outside controlled clinical trials. The real value of
      regional chemotherapy must be evaluated in larger, randomized trials. New drug
      combinations may reduce the observed side effects and improve tumor response.
      Gene therapy with p53 and K-ras modulated herpesviruses may become a palliative
      treatment option and can be administered easily by regional chemotherapy
      techniques [23].

PMID- 12063828
TI  - Early detection of pancreatic carcinoma.
AB  - The poor prognosis and late presentation of pancreatic cancer patients emphasize
      the importance of an effective early detection strategy for patients at risk of
      developing pancreatic cancer. In current practice, the use of CA 19-9 levels and
      imaging techniques is not optimal for detecting small pancreatic lesions. It is
      hoped that the understanding of genetic alterations in combination with the
      development of high-throughput sensitive techniques will lead to the rapid
      discovery of a panel of biomarkers that will save lives by enabling aggressive
      therapy at the time when tumors are curable.

PMID- 12063829
TI  - Interventional endoscopy, neoadjuvant therapy and the gastroenterologist.
AB  - With current treatment, survival of greater than 1 year should be anticipated for
      many patients with pancreatic cancer. Cure rates (5-year survival) of greater
      than 10% have been achieved even for unresectable disease. Obstructive jaundice
      is managed successfully with endoscopic placement of a plastic stent early in the
      evaluation of a patient with suspected regional pancreatic cancer, and a metal
      wall stent is reserved for patients with known 1997 AJCC stage IVB carcinoma or
      nonoperative patients. Relief of biliary obstruction allows improvement in liver
      function and more time to evaluate tumor stage accurately to determine initial
      treatment (see Fig. 1). A cost-effective algorithm to determine accurate stage
      and treatment can start with the size of the mass on initial imaging studies. EUS
      guided FNA represents a significant improvement over CT scan-guided FNA to make a
      tissue diagnosis. Small pancreatic masses that would be resected regardless of
      whether an FNA is positive or negative require only an EUS evaluation to
      establish an early resectable stage. Tumors reliably staged as unresectable by
      nonoperative imaging methods including EUS are treated with chemotherapy with or
      without concurrent radiotherapy because median survival of these patients is 2
      years in some series. Tumors can be resected after neoadjuvant chemoradiotherapy.
      For chronic pain or gastric outlet obstruction not responding or treatable by
      chemoradiotherapy, endoscopically guided celiac plexus nerve block and stenting
      improve the quality of life for patients with pancreatic cancer. A team approach
      is required to achieve the objectives of improved quality of life, prolonged
      survival, and possible cure for pancreatic cancer. The optimal combination and
      sequencing of staging methods, including EUS, specialized CT scan, MR imaging,
      intraoperative findings, and pathologic evaluations, would improve selection of
      patients for potential curative resection. Interpretations of disease stage based
      on each of these methods may overlap but are not identical and are operator
      dependent. Rather than reliance on any single standard, clinical judgment and
      communication among the team are paramount to providing optimal care for patients
      with a pancreatic neoplasm.

PMID- 12063830
TI  - Surgery and cancer of the pancreas: will common sense become common practice?
AB  - Pancreatic cancer is a systemic disease for most patients. Operations with the
      intent to cure may be done safely (mortality, < 3%) with shorter hospital stays.
      Surgery has been minimally effective as a long-term cure. Endoscopic palliation
      of jaundice is becoming standard practice. Common sense dictates a defined and
      clear role for surgery (i.e., strict patient selection criteria). Surgery is of
      great value for small, localized lesions; of clear value as palliative therapy
      when nonoperative measures fail; and perhaps best applied after neoadjuvant
      chemoradiotherapy. Surgery is just part of the armamentarium available to treat
      pancreatic cancer. Novel systemic therapies, including chemotherapy,
      immunotherapy, and so-called targeted therapies, are becoming increasingly
      valuable in the management of this systemic disease and are discussed in detail
      in other articles in this issue.

PMID- 12063832
TI  - Bioterrorism: what is and what may never be. Part 1.

PMID- 12063831
TI  - Management of locally advanced adenocarcinoma of the pancreas.
AB  - Pancreatic cancer is one of the deadliest malignancies and is fatal in more than
      95% of affected individuals. For locally advanced disease, the combination of 5
      FU and radiation appears to offer the best chance for delaying disease
      progression. The introduction of gemcitabine into chemoradiotherapy regimens may
      provide additional improvements in the management of patients. Preoperative
      therapy has proved feasible but has not shown improvement in overall survival.

PMID- 12063833
TI  - Introduction to clinical guideline series.

PMID- 12063834
TI  - Guideline for diagnosis of celiac disease.

PMID- 12063835
TI  - From physician to inmate.

PMID- 12063836
TI  - Medical care at hospitals in the 21st century.

PMID- 12063837
TI  - Development of "Standards for the Evaluation of Hospital Infection Control
      Policies and Procedures, the Second Version".
AB  - The Japan Society for Quality in Health Care (JSQua) created "Standards for the
      Evaluation of Hospital Infection Control Policies and Procedures, the First
      Version" in 1998 and carried out third-party surveys. Through the experience of
      those surveys, we revised the standards and created a second version in 1999. The
      surveyors felt that in using the second version of the standards it would be
      easier to evaluate the quality of hospital care and that these standards would be
      more widely applied.

PMID- 12063838
TI  - A new social care insurance in Japan on 1 April 2000.

PMID- 12063839
TI  - Outline of the medical insurance system in Japan--the change on 1 January 2001.

PMID- 12063840
TI  - Health care reform in Japan--IHF Pre-Congress Health Summit Programme May 14,
      2001, Hong Kong.

PMID- 12063841
TI  - The construction of the population dynamic model for the estimation of the total
      medical care needs in Japan.

PMID- 12063842
TI  - Healthcare reform--myth or reality.

PMID- 12063843
TI  - Neural stem cells of the mammalian forebrain.

PMID- 12063844
TI  - Stem cells and regeneration in invertebrate Deuterostomes.

PMID- 12063845
TI  - Similarity and differences between the haemopoietic and brain stem cell system.

PMID- 12063846
TI  - Lineage selection and isolation of neural precursors from embryonic stem cells.

PMID- 12063847
TI  - Early generated Cajal-Retzius cells have different functions in cortical
      development.

PMID- 12063848
TI  - Signalling cascade of CNR cadherins (Reelin receptors) in the mammalian brain.

PMID- 12063849
TI  - The role of the Reelin pathway in cortical development.

PMID- 12063850
TI  - The Drosophila nervous system as a model for asymmetric cell division.

PMID- 12063851
TI  - Developmental abnormalities in early-onset hydrocephalus: clues to signalling.

PMID- 12063852
TI  - [Effect of the Chernobyl plant accident on the health state of the Hungarian
      population].

PMID- 12063853
TI  - [Radiation effects of the Chernobyl accident on the Hungarian population].
AB  - Due to the nuclear accident at Chernobyl in April 1986, the atmospheric transport
      spread the released radioactivity throughout the whole Europe. The initial plume
      moved into the north-western direction and a portion of this plum turned to west
      and later on to south-west. The central European countries including Hungary
      became affected in 29-30 April. The release during the last period (5-7 May) was
      directed to Romania, Bulgaria and Greece. In addition to the main trajectories of
      the atmospheric transport, the local meteorological conditions with winds of
      different directions at various altitudes, rainfalls etc. produced a very complex
      deposition pattern in Central Europe. The contamination of the soil surface and
      vegetation were strongly influenced by the wash-out of the radioactive materials
      from the local air. Due to the high geographical variation of the rains the
      surface contamination provided a similar heterogeneity among the territories of
      the country. The northern-west part and the region of the capital Budapest became
      nearly 5 times higher contaminated than the middle part of the country. Radiation
      doses of the population have been provided by activity concentrations in air,
      soil, vegetation, foods etc. and the external dose rates, mainly due to the
      surface contamination by the isotopes of 131I, 134Cs and 137Cs. The average
      effective dose contribution received by the individuals (adults) in Hungary
      during the 15 years following the accident has been assessed to be 0.30 mSv while
      the annual dose from the natural background is 2.5-3 mSv. Contribution to total
      dose from the internal pathway (committed effective dose) resulted about 0.10 mSv
      and the external radiation provided 0.19 mSv. The contributions of the external
      exposure from the contaminated air and inhalation are less than 5% of the total
      one.

PMID- 12063854
TI  - [Fatty acid composition of colostrum and mature human milk in Hungary].
AB  - INTRODUCTION AND AIMS: Because of the lack of up-to-date data on fatty acid
      composition of human milk in Hungary, the authors analysed fatty acid composition
      of colostrum (n = 18, one hind milk sample on day 5 after delivery) and mature
      milk (n = 15, pooled 24 h collections repeated twice with 2 weeks intervals at
      median duration of lactation of 4 months) samples with high-resolution capillary
      gas chromatography. RESULTS: Fat content and fatty acid compositions did not
      differ in 24 h pooled mature human milk samples obtained with 2 weeks intervals.
      Significantly lower values of linoleic acid [10.98 (4.81) vs. 14.70 (5.32), %
      w/w, median (range from the 1st to the 3rd quartile), colostrum vs. mature human
      milk, p < 0.001] and alpha-linolenic acid [0.22 (0.09) vs. 0.68 (0.21), p <
      0.0001], and significantly higher values of arachidonic acid [0.70 (0.56) vs.
      0.50 (0.12), p < 0.001] and docosahexaenoic acid [0.22 (0.15) vs. 0.18 (0.06), p
      < 0.05] were found in colostrum than in mature human milk. Significant and
      positive correlations were seen between linoleic and arachidonic (r = 0.71, p =
      0.001) as well as between alpha-linolenic and docosahexaenoic (r = 0.59, p =
      0.01) acid values in colostrum, but not in mature human milk. CONCLUSION: While
      mature human milk linoleic, arachidonic and alpha-linolenic acid values in this
      study were in the range usually reported in the literature, the contribution of
      docosahexaenoic acid to the fatty acid composition of human milk was considerably
      lower in Hungary than in several other populations.

PMID- 12063855
TI  - [Proteomics in clinical enzymology: polymorphism of creatine kinase and alkaline
      phosphatase].
AB  - INTRODUCTION: The clinical proteomics is dedicated to the use of the proteomics
      in the clinical laboratory science. AIMS: Examples for the importance of clinical
      proteomics are provided by studies on the polymorphisms of creatine kinase and
      alkaline phosphatase enzymes. METHODS: The different (immunoinhibition,
      electrophoretic, immunochemistry) assays for determination of a cardiac marker
      (creatine kinase 2) are compared in hospital patients. Isoform analysis of
      alkaline phosphatase is performed in benign, transient hyperphosphatasemia.
      RESULTS: The author reviews recent knowledge on polymorphism of creatine kinase
      (isoenzymes, isoforms, macro types), and alkaline phosphatase (isoenzymes, their
      cancer related variants, isoforms). The origin of falsely high cardiac marker
      (creatine kinase 2) determined by the immunoinhibition assay could be related to
      the presence of macro creatine kinase (both types), creatine kinase isoenzyme 1,
      and their mixtures. After reviewing the recent findings on the syndrome of
      benign, transient hyperphosphatasemia, a case of a 1-year-old Hungarian boy with
      this syndrome is presented. CONCLUSIONS: The author points out that the
      appropriate use of clinical proteomics (the polymorphisms of creatine kinase and
      alkaline phosphatase enzymes) may improve the diagnostic efficiency of the
      clinical laboratory tests.

PMID- 12063856
TI  - [Effect of ubiquinone and other scavengers on alterations caused by oxidative
      stress].
AB  - In the development of several diseases the oxidative stress is a significant
      aetiological or important pathogenetic factor. Its significance has been proved
      in the pathogenesis of several diseases, among them in arteriosclerosis and
      reperfusion, in inflammation and immunological disorders, as well as in toxic
      alterations and in carcinogenesis. The increased incidence of malignant tumors
      may be attributed to smoking, intemperate alcohol abuse, as well as inappropriate
      nutrition. Inappropriate nutrition is thought to be responsible for the
      development of about 30-50% of malignancies. In this paper the authors review the
      processes of the development of free radicals based on oxygen and nitrogen. They
      discuss the modalities which are able to decrease the oxidative stress, like the
      low oxygen tension in the tissues, the enzymatic and antioxidant protections, and
      the different repair mechanisms. In details the roles of ubiquinone, with other
      name of coenzyme Q, as well as of the selenium are discussed in the antioxidant
      defence processes. As a conclusion they suppose that oxidative stress in the
      organism and the alterations caused by them can be decreased by adequate
      nutrition or nutriceuticals.

PMID- 12063857
TI  - [Upper respiratory signs and symptoms in gastroesophageal reflux disease].

PMID- 12063858
TI  - [Cross-reaction potentials of ketoprofen].

PMID- 12063859
TI  - [Acromegaly: a disorder with distinguished features yet delayed diagnosis].
AB  - The authors review the historical and epidemiological aspects, as well as the
      distinguishing clinical features and complications of acromegaly to emphasize the
      importance of early diagnosis and treatment of patients with this disorder.
      Acromegaly is a rare disorder with a prevalence of 55-69 cases per million
      population and an incidence of 3-4 newly detected cases per million per year.
      Recent estimates indicate, that its slow progression and insidious course leads
      to a considerable time lag of 7-12 years between the first symptoms and the
      diagnosis of the disease, although younger patients with more severe disease may
      be detected earlier. In addition to the disfigurement and disability which
      develop progressively from the onset of the disease, acromegaly is associated
      with a number of complications resulting in a two- or three-fold increase of
      mortality and a decrease of life expectancy by about 10 years. The major causes
      of death include cardiovascular and cerebrovascular events, respiratory disease
      and malignancy. Because the duration of the disease before effective therapy may
      be one of the major predictors of increased mortality, practicing doctors need to
      be particularly vigilant to recognize undiagnosed cases in order to avoid the
      serious complications of the disease.

PMID- 12063860
TI  - [Novel pharmacologic therapies in acromegaly].
AB  - The primary aim of therapy should be to remove symptoms, reduce tumor bulk,
      prevent relapse, and improve long-term outcome. Surgery, radiotherapy and medical
      therapies are used to achieve these aims. Post-treatment mean "safe" serum growth
      hormone values of < 2.5 ng/ml should be the therapeutic goal. Transsphenoidal
      surgery remains the first line treatment for acromegaly. Patients with
      microadenoma can expect 85%, while those with macroadenoma 50% chance to achieve
      safe serum growth hormone levels. Less than 20% of acromegalics respond to
      treatment with bromocriptine, while quinagolide and cabergoline may show better
      clinical response; the success rate is higher for tumors secreting both growth
      hormone and prolactin. Dopamine agonists may be considered either in combination
      with somatostatin-analogues or as monotherapy in selected patients, and in those
      with co-secretion of prolactin. Octreotide (Sandostatin, Novartis) is a synthetic
      somatostatin-analogue, which is administered subcutaneously in doses between 100
      and 250 micrograms 3 times daily. Long-acting octreotide (Sandostatin LAR,
      Novartis) contains octreotide incorporated into microspheres of biodegradable
      polymer. To effectively lower serum growth hormone levels, monthly injections of
      10-30 mg of long-acting octreotide are needed, serum growth hormone falls to 2.5
      ng/ml in 70% of cases, and serum insulin-like growth factor I normalizes in 67%.
      Slow release lanreotide (Somatuline SR, Ipsen) is an alternative depot long
      acting somatostatin-analogue, which is administered in a dose of 30 mg
      intramuscularly every 14, 10 or 7 days. Both compounds are equally, if not more,
      effective than subcutaneous octreotide, and significantly improve patient
      compliance. Pegvisomant (Sensus Drug Development Corporation) is a genetically
      engineered growth hormone receptor antagonist, which inhibits growth hormone
      action. When given subcutaneously in a dose of 20 mg/day, serum insulin-like
      growth factor I levels return to normal in 90% of patients. Theoretical concerns
      of tumor expansion have not been a problem to date, but long term studies are
      needed. Primary medical--somatostatin-analogue--therapy is recommended if surgery
      fails, if the patient refuses or unsuited for surgery and it may be also
      considered in patients with macroadenoma with extra--but not suprasellar
      extension, since the surgical "cure" rates of these tumors are low.

PMID- 12063861
TI  - [Current alternative in the pharmacotherapy of acromegaly: the long-acting
      somatostatin analogue octreotide].
AB  - Twelve active acromegalic patients (10 women, 2 men) were chronically treated
      with a long-acting microcapsulated preparation of octreotide (Sandostatin LAR,
      Novartis). In each case, a growth hormone-producing pituitary adenoma was
      responsible for the development of acromegaly (microadenomas in 3 and
      macroadenomas in the rest of the patients). Treatment with long-acting octreotide
      was indicated for those patients who had not reacted satisfactorily upon previous
      therapeutic procedures or proved to be unsuitable for irradiation therapy and/or
      surgery or refused both of these therapies. The preparation was given
      intramuscularly in every fourth week, generally in a dose of 20-30 mg. After a 6
      month treatment, the daily mean of serum growth hormone became suppressed below
      2.5 ng/ml in 58.3% of the patients, whereas the growth hormone nadir during oral
      glucose tolerance test was found at or below 2.5 ng/ml in an even higher
      proportion of patients (70%). During a 2-year period, the growth hormone
      suppressive effect of long-acting octreotide remained stable in all but one
      patient. The size of the pituitary adenomas remarkably decreased in 50% of this
      patient cohort. The medication with this preparation was well tolerated. As
      adverse events, asymptomatic cholelithiasis was detected in 2 patients and
      biliary sludge-formation in 1 patient. The total number of patients with glucose
      metabolism disturbances increased only moderately, however, the occurrence of
      manifest diabetes mellitus became doubled. On the basis of relevant literature
      data, it can be stated that the mortality rate of successfully treated
      acromegalics significantly improves. The present retrospective study yields
      evidence for the microcapsulated octreotide to be an effective tool in the modern
      therapy of acromegaly.

PMID- 12063862
TI  - [Experience in treating acromegalic patients with long-acting octreotide].
AB  - The authors report clinical observations in 12 acromegalic patients treated with
      long-acting octreotide (Sandostatin LAR, Novartis, 20 mg intramuscular injection
      per 28 days administered for 6-36 months). Clinically and hormonally active
      acromegaly was evidenced in all patients by the presence of typical clinical
      symptoms, increased serum growth hormone and insulin-like growth factor I
      concentrations, and by non-suppressible serum growth hormone levels after oral
      glucose administration. In all patients previous treatments (transsphenoidal
      surgery, pituitary irradiation and bromocriptine therapy) were uneffective or
      contraindicated, or they were refused by the patients. Octreotide test
      (Sandostatin, Novartis, 100 g subcutaneously) performed in all patients before
      treatment precisely predicted the hormonal effectiveness of long-acting
      octreotide treatment. Three-six months after therapy serum growth hormone levels
      decreased from 13.6 +/- 3.9 ng/ml (mean +/- SD) to 3.4 +/- 1.7 ng/ml, while
      insulin-like growth factor I concentrations decreased from 483 +/- 127 ng/ml to
      248 +/- ng/ml. Of the 12 patients 7 (58%) had serum growth hormone levels
      considered as safe values (< 2.5 ng/ml), whereas in 9 patients (75%) serum
      insulin-like growth factor I concentrations returned to age- and sex-matched
      normals. Repeat pituitary magnetic resonance imaging performed in 8 patients
      treated longer than 1 year revealed a decrease of tumor size in 3 patients (37%).
      There was a considerable clinical improvement during treatment: severe headache,
      which was present in most patients, as well as perspiration, joint pain, swelling
      of extremities, and weakness markedly decreased or disappeared. These results
      indicate that long-acting octreotide offers a very effective treatment of choice
      in acromegalic patients in whom other previous therapies were ineffective,
      contraindicated, or refused.

PMID- 12063863
TI  - [Acromegaly associated with McCune-Albright syndrome].
AB  - McCune-Albright syndrome is characterized by polyostotic fibrous dysplasia, cafe
      au lait pigmentation of the skin, and multiple endocrinopathies. The authors
      report a history of a 30-years-old man who had a pathologic humerus fracture at
      the age of 14 years. The diagnosis of polyostotic fibrous dysplasia was
      established by radiologic examinations and bone biopsy. Fourteen years
      thereafter, active acromegaly due to a pituitary microadenoma was diagnosed using
      hormone measurements and pituitary magnetic resonance imaging. Pituitary surgery
      was refused because of an extensive skull involvement caused by the fibrous
      dysplasia. After an unsuccessful therapy with bromocriptine lasting three months,
      long-acting octreotide (Sandostatin LAR, Novartis) treatment was started. After a
      12-months course of treatment, serum growth hormone levels markedly decreased,
      clinical symptoms improved, but serum insulin-like growth factor I levels
      remained unchanged. These observations that serum insulin-like growth factor I
      levels failed to reflect the decrease of serum growth hormone concentrations
      after long-acting octreotide treatment suggest that the increased production of
      insulin-like growth factor I in patients with acromegaly due to McCune-Albright
      syndrome may involve mechanism(s) other than increased growth hormone levels.

PMID- 12063864
TI  - [Thyrotropin-secreting pituitary adenomas--diagnosis and treatment in five case].
AB  - The authors report five cases of thyrotropin secreting pituitary adenomas (4
      males and 1 female) in whom the diagnosis was established by a combined
      occurrence of elevated serum free thyroid hormone levels and measurable serum
      thyrotropin concentration, as well as by visualisation of the pituitary adenomas
      using magnetic resonance imaging (pituitary microadenoma in two and macroadenoma
      in three cases). Other tests were less diagnostic: only two out of 4 patients
      proved to be non-responders during testing with thyrotropin releasing hormone,
      and serum alpha subunit was elevated in only 2 out of 3 cases. There was a
      significant decrease of serum thyrotropin concentration in all of the four
      patients tested by 100 micrograms octreotide (Sandostatin, Novartis).
      Somatostatin-analogue treatment (slow release preparation in two cases) restored
      euthyroidism in all three cases treated prior to surgery. In one case the
      hyperthyroidism persisted after surgery of the macroadenoma, but irradiation of
      the pituitary area and subsequent somatostatin-analogue treatment resulted
      finally in a complete cure (euthyroidism and no tumor remnant). In the three
      other operated patients surgery resulted in euthyroidism. These cases demonstrate
      the variety of diagnostic and therapeutical modalities in the management of
      thyrotropin secreting pituitary adenomas.

PMID- 12063865
TI  - [Octreotide therapy in multiple endocrine neoplasia type-1].
AB  - In multiplex endocrine neoplasia type 1, hyperparathyroidism, pancreas tumor and
      pituitary tumor are generally combined. The authors report two patients with this
      syndrome, in whom overproduction of parathormone and gastrin was detected, and
      parathyroid adenomas were detected by parathyroid scintigraphy. Pancreatic
      adenomas were discovered with somatostatin receptor scintigraphy or magnetic
      resonance imaging. Hyperprolactinaemia without pituitary tumor in the first case,
      and prolactinoma in the second case, as well as nonfunctioning adrenal adenomas
      in both cases were also observed. After several unsuccessful surgical
      interventions a long-term octreotide (Sandostatin, Novartis) treatment was
      started; in the first patient subcutaneous injection was given for 6 months, then
      the treatment was continued with the long-acting intramuscular preparation
      (Sandostatin LAR, Novartis). The second patient received long-acting octreotide
      from the beginning of medical therapy. The authors intended to obtain data about
      the effects of this therapy on all overproduced hormones. In the first case, a 6
      months treatment with subcutaneous octreotide surprisingly resulted not only in a
      decrease of serum gastrin, but also in that of parathormone level. In the second
      case, serum gastrin was normalized, but parathormone did not change. The levels
      of prolactin and adrenocortical hormones were not affected. At present, the two
      patients are without any symptoms of their disease.

PMID- 12063866
TI  - [Neuroendocrine tumors of the digestive system].
AB  - Despite their rare occurrence, gastroenteropancreatic neuroendocrine tumors have
      been in the centre of interest because of the wide scale and variability of
      clinical signs and symptoms associated with oversecretion of different hormones.
      In the present review the authors summarize epidemiological data, pathologic
      findings, clinical symptoms, as well as diagnostic and therapeutic methods
      presently available for the management of patients with gastroenteropancreatic
      neuroendocrine tumors. In addition to surgical treatment and receptor-specific
      radionuclide therapy used in cases with surgically noncurable tumors, the
      therapeutic use of somatostatin analogues in recent years has resulted an
      important advance in the management of patients with these tumors. Somatostatin
      analogues alone or in combination with other pharmacological therapies may be
      used effectively for elimination of symptoms of hormonal oversection and, in a
      number of cases, for diminishing tumor progression.

PMID- 12063867
TI  - [Carcinoid tumors].
AB  - Carcinoids are characteristically indolent, but heterogeneous tumors with respect
      to their site of origin, endocrine features, clinical manifestations and biologic
      behaviour. The authors summarize the current laboratory, endoscopic and
      radiologic methods used for the diagnosis of carcinoid tumors. Treatment
      modalities should be directed against the tumor and the hormonal excess state.
      The authors review the outcome of most frequently used therapies, including
      somatostatin-analogue and interferon treatment, chemotherapy, embolization,
      receptor-targeted radiotherapy and surgical intervention). Patients with
      carcinoid tumors, with or without carcinoid syndrome, are best managed by a
      multidisciplinary approach.

PMID- 12063868
TI  - [Role of somatostatin in the management of upper gastrointestinal bleeding].
AB  - There exists a substantial basis of experimental and clinical data to support
      that somatostatin and its long acting synthetic analogue octreotide may be
      therapeutically efficacious either as primary or adjunctive therapy in subgroups
      of patients with upper gastrointestinal bleeding. It has been proposed that
      somatostatin represents the optimal drug treatment for acute variceal bleeding
      due to its efficacy, its simplicity of administration and its lack of significant
      side effects. It provides beneficial respite if endoscopic therapy cannot be
      performed immediately. Somatostatin also facilitates the performance of
      diagnostic and of non-pharmaceutic interventions. Despite strong theoretical
      evidence in support of the application of somatostatin to the control of acute
      nonvariceal gastrointestinal bleeding, clinical trials have yielded conflicting
      results.

PMID- 12063869
TI  - [Somatostatin in the treatment of pancreatic diseases].
AB  - Somatostatin and its synthetic analogues have important physiological roles in
      human. These compounds antagonize the endocrine and exocrine secretion of
      pancreas, which provide theoretical ground for their use in patients with
      pancreatic diseases. For a quarter of a century many researchers have
      investigated the effect of somatostatin and octreotide in animal models of
      experimental pancreatitis and in patients with acute pancreatitis, and in those
      with complications of pancreatic operations, fistulas and pseudocysts. In most of
      these studies the use of synthetic octreotide with longer duration proved to be
      more efficient. In experimental and acute pancreatitis somatostatin and
      octreotide were less effective than expected, however, they proved to be helpful
      in preventing complications of pancreatic operations and in the therapy of
      fistulas and pseudocysts.

PMID- 12063870
TI  - Recent advances in the management of gestational trophoblastic disease: a
      symposium.

PMID- 12063871
TI  - Advances in the understanding of placental site trophoblastic tumor.
AB  - Placental site trophoblastic tumor (PSTT) is the least common form of gestational
      trophoblastic disease. The tumor represents a neoplastic transformation of
      intermediate trophoblastic cells that normally play a critical role in
      implantation. PSTT can occur after a normal pregnancy, spontaneous abortion,
      termination of pregnancy, ectopic pregnancy or molar pregnancy. It displays a
      wide spectrum of behavior, and when metastatic, can be difficult to control even
      with surgery and chemotherapy. Because of PSTT's rarity, limited information is
      known about its natural history. Several recent studies have indicated that
      mitotic index is an important prognostic indicator. Advances in chemotherapeutic
      regimens have also improved clinical response in metastatic disease.

PMID- 12063872
TI  - Ploidy and imprinting in hydatidiform moles. Complementary use of flow cytometry
      and immunohistochemistry of the imprinted gene product p57KIP2 to assist molar
      classification.
AB  - OBJECTIVE: To determine whether the combination of flow cytometry and
      immunohistochemistry for p57 expression is useful for the pathologic
      classification of diagnostically challenging hydatidiform moles. STUDY DESIGN:
      Six probable hydatidiform moles that were difficult to classify pathologically
      were reevaluated by histology, flow cytometry and immunohistochemistry for p57.
      RESULTS: In all cases, the pathologic diagnoses were easily resolved: two cases
      were partial moles (triploid, p57 positive), two cases were early complete moles
      (diploid, p57 negative), and two cases were twin gestations with normal villi
      (diploid, p57 positive) admixed with villi from a complete hydatidiform mole
      (diploid, p57 negative). CONCLUSION: Immunostaining for the paternally imprinted,
      maternally expressed p57 gene product is a practical and accurate adjunct to flow
      cytometry in the pathologic classification of hydatidiform moles.

PMID- 12063873
TI  - Current management of molar pregnancy.
AB  - Molar pregnancy remains an uncommon and still not fully understood disorder. The
      clinical presentation has changed over recent decades. In developed countries
      complete moles are now usually diagnosed early (on clinical and/or ultrasound
      scan criteria) so that the more severe clinical presentations are much less
      commonly seen. The important differences between complete and partial moles and
      their risk factors are now well recognized. Common protocols for managing
      persistent gestational trophoblastic disease are being derived, and molecular
      genetic studies are advancing our understanding of molar pregnancy and its
      sequelae. Cure rates approaching 100% should now be the rule rather than the
      exception. There is a strong case for formal registration and monitoring of all
      cases through specialist centers.

PMID- 12063874
TI  - Methotrexate infusion and folinic acid as primary therapy for nonmetastatic and
      low-risk metastatic gestational trophoblastic tumors. 15 years of experience.
AB  - OBJECTIVE: To investigate the efficacy and toxicity of methotrexate (MTX) given
      intravenously (i.v.) at a dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion
      over 12 hours followed by folinic acid in the primary treatment of gestational
      trophoblastic tumors (GTTs). STUDY DESIGN: We reviewed the records of patients at
      the New England Trophoblastic Disease Center who had received MTX infusion at a
      dose of 100 mg/m2 i.v. bolus and 200 mg/m2 infusion over 12 hours followed by
      folinic acid as primary therapy for GTTs that did not resolve with uterine
      evacuation alone. Data on the patients' age, gravity and parity, disease stage
      (by FIGO and WHO criteria), antecedent pregnancy, presenting level of hCG,
      metastatic status, courses of chemotherapy required to achieve remission,
      toxicity related to chemotherapy treatments and time to normalization of hCG were
      recorded. RESULTS: One hundred ninety-two patients with persistent GTTs were
      treated with the MTX infusion protocol between December 1985 and December 2000.
      One hundred twenty-four patients (64.6%) achieved complete remission with the MTX
      infusion protocol. Complete remission was induced in 108 (87.1%) with a single
      course of chemotherapy; 12 others achieved remission with a single additional
      course of MTX. All patients found to be resistant to MTX therapy later achieved
      remission with other chemotherapy. Minimal toxicity was experienced during MTX
      treatment. CONCLUSION: MTX infusion with folinic acid is effective and well
      tolerated as primary single-agent therapy for nonmetastatic and low-risk
      metastatic GTT.

PMID- 12063875
TI  - Recent advances in molecular biology of gestational trophoblastic diseases. A
      review.
AB  - Gestational trophoblastic diseases are interrelated conditions characterized by
      abnormal growth of chorionic tissues with various propensities for local invasion
      and metastasis. Complete mole is a unique conception in that all nuclear DNA is
      paternally derived and all cytoplasmic DNA is maternally derived. In contrast,
      partial mole generally has a triploid karyotype, where the extra haploid set of
      chromosomes is paternally derived: Gestational trophoblastic diseases are
      characterized by altered expression of several growth regulatory factors and
      oncogenes. While differences in expression of oncoproteins may be important to
      the development of gestational trophoblastic disease, the precise molecular
      changes that are critical to pathogenesis remain unknown.

PMID- 12063876
TI  - Subsequent pregnancy experience in patients with molar pregnancy and gestational
      trophoblastic tumor.
AB  - Modern therapy for molar pregnancy and gestational trophoblastic tumors has
      resulted in high cure rates and preservation of fertility, even in the setting of
      metastatic disease requiring chemotherapy. Patients and their partners facing
      future pregnancy after treatment for gestational trophoblastic disease express
      fear related to risk of disease recurrence and outcome of subsequent pregnancies.
      Data from the New England Trophoblastic Disease Center on later pregnancies
      following complete and partial mole as well as persistent gestational
      trophoblastic tumor show that patients, in general, can anticipate normal
      subsequent pregnancy outcomes.

PMID- 12063877
TI  - Quality of life after gestational trophoblastic disease.
AB  - OBJECTIVE: To describe the quality of life (QoL) and long-term psychosocial
      sequelae in women diagnosed with gestational trophoblastic tumor (GTT) 5-10 years
      earlier. STUDY DESIGN: Utilizing a cross-sectional descriptive design, 111
      survivors completed a comprehensive QoL interview. RESULTS: Participants were
      predominantly married and non-Hispanic white, with a mean age at diagnosis of 30
      years and a current mean age of 37 years. This disease-free sample enjoys a good
      QoL, with physical, social and emotional functioning comparable to or better than
      comparative norms. However, certain psychological survivorship sequelae persist.
      Additionally, a sizable number of survivors currently experience significant
      reproductive concerns. Participants reporting good QoL were less likely to report
      ongoing coping efforts related to having had this illness, more likely to report
      greater social support (P < .0001), greater sexual pleasure (P = .0063), and less
      GTT-specific distress (P < .0001). Fifty-one percent of respondents expressed
      that they would likely participate in a counseling program today to discuss
      psychosocial issues raised by having had GTT, and 74% stated that they would have
      attended a support group program during the initial treatment if it had been
      offered. CONCLUSION: This information provides insight into the complex
      survivorship relationships between QoL and sequelae of GTT.

PMID- 12063878
TI  - Treatment of vulvar intraepithelial neoplasia 2/3 with imiquimod.
AB  - OBJECTIVE: To retrospectively review the charts of 13 women diagnosed with vulvar
      intraepithelial neoplasia (VIN) 2/3 treated with imiquimod and to evaluate the
      efficacy of this treatment. STUDY DESIGN: Retrospective review. All 13 women were
      treated and evaluated by a single gynecologist. The extent of the lesions prior
      to treatment and the extent and degree of improvement were documented. Biopsy
      confirmation of disease was obtained for each individual. Response to treatment
      was categorized as complete regression, at least 75% regression or not improved.
      RESULTS: The mean duration of treatment was 3.3 months, and follow-up after
      completion of therapy was 5.5 months. Eight of the 13 women had complete
      regression of the VIN. Four patients demonstrated 75% regression of disease, and
      in one diabetic woman no improvement was seen. In two women demonstrating 75%
      lesion regression, invasive carcinoma of the vulva was found in the area of
      residual disease. In one instance this was determined to be superficially
      invasive squamous cell carcinoma (1 mm of invasion), and in the second an anal
      tag was found to have invasive squamous cell carcinoma. CONCLUSION: Medical
      management of VIN 2/3 with imiquimod is worth considering. However, careful
      evaluation of the patient must be carried out prior to the institution of therapy
      to exclude the presence of invasive squamous cell carcinoma.

PMID- 12063879
TI  - Elective induction of labor in multiparous women. Does it increase the risk of
      cesarean section?
AB  - OBJECTIVE: To determine whether the medical initiation of labor places the
      multiparous woman at increased risk of cesarean section. STUDY DESIGN: This study
      was a retrospective, case-control assessment of the risk of cesarean section in
      multiparas with no medical or obstetric complications and vertex presentations
      whose induction of labor at term was judged to be elective by chart analysis.
      Case women were matched for age, parity, gestational age and staff obstetrician
      with controls in spontaneous labor, and the rates of cesarean delivery were
      compared. RESULTS: Three hundred four case-control pairs were studied. No
      significant difference was observed in the rate of cesarean delivery between the
      two groups. The rate of cesarean section in the electively induced group was 3.6%
      versus 4.3% in the control group (P = .6670). Neither cervical state nor use of
      cervical ripening agents significantly affected the rate of cesarean delivery.
      CONCLUSION: As compared with spontaneous labor, the elective induction of labor
      in multiparous women without complications does not predispose to cesarean
      delivery.

PMID- 12063880
TI  - Detection of alcohol and drug problems in an urban gynecology clinic.
AB  - OBJECTIVE: To compare screening instruments for their utility to detect substance
      use problems in women seeking gynecologic care, to assess the likelihood that
      alcohol/drug problems will be detected by physicians during a routine office
      visit and to examine the relationship between regular alcohol and/or drug use and
      the patient's presenting gynecologic complaints. STUDY DESIGN: Women (N = 360)
      attending a hospital-based gynecology clinic were screened prior to physician
      visit using the Michigan Alcoholism Screening Test, CAGE and T-ACE. After the
      visit, information on presenting complaint and physician's documentation of the
      patient's tobacco, alcohol and other drug use was abstracted from the medical
      record. RESULTS: The rates of alcohol and illicit drug use varied across
      assessment instruments; physician documentation, however, yielded the lowest
      prevalence estimates. Regular alcohol and drug users were more likely to present
      with chronic and acute medical problems than patients who were not regular users
      of these substances. CONCLUSION: The gynecology clinic offers an opportunity for
      early identification of women with substance problems, and alternative strategies
      are needed to encourage gynecologists to routinely screen for such problems at
      each medical visit.

PMID- 12063881
TI  - The FORKO mouse as a genetic model for exploring estrogen replacement therapy.
AB  - OBJECTIVE: To evaluate how chronically estrogen deficient female FORKO mice with
      genetic disruption of the FSH receptor respond to estrogen therapy. STUDY DESIGN:
      Subcutaneous estrogen agonist or antagonist therapy was initiated to study
      reproductive tissue response, adipose tissue mass and plasma lipid profiles.
      RESULTS: Within 36-48 hours of agonist administration, the classic measures of
      estrogenic activity were evident in the uterus and vagina. Older animals also
      responded to therapy during a 10-day period, indicating that estrogen receptor
      signaling systems are unaffected by aging. In these obese mutants, this short
      treatment decreased adipose tissue in all areas and corrected lipid
      abnormalities. Tamoxifen, a nonsteroidal mixed estrogen agonist and antagonist,
      had marginal effects on the uterus and body fat of FORKO mice, indicating
      differences in interaction. CONCLUSION: In FORKO mice lacking ovarian estrogen,
      the receptors remain fully functional. Hence, this is a useful model for studying
      estrogen replacement therapy and helps resolve questions related to efficacy and
      actions.

PMID- 12063882
TI  - Spontaneous subserosal venous rupture overlying a uterine leiomyoma. A case
      report.
AB  - BACKGROUND: Patient age, parity and leiomyoma size are considered risks for
      venous rupture overlying a leiomyoma. CASE: A 28-year-old woman presented with
      abdominal pain and decreasing hematocrit from spontaneous rupture of a uterine
      leiomyoma vein. CONCLUSION: Congestion of a vein overlying a leiomyoma,
      irrespective of the patient's age or parity or size of the leiomyoma, is a risk
      factor for rupture.

PMID- 12063883
TI  - Pregnancy complicated by acute pulmonary lymphangitic adenomatosis, metastasis
      and disseminated intravascular coagulation. A case report.
AB  - BACKGROUND: The association of pregnancy and cancer is a rare event, occurring in
      less than 1 case per 5,000 pregnancies, and is a cause of maternal mortality in
      about 5% of cases. CASE: A 33-year-old, Japanese woman presented at the end of
      pregnancy with clinical manifestations of pneumonia and developed fatal
      disseminated intravascular coagulation in the postpartum period. The pathologic
      findings suggested the existence of a primary cancer in the gastrointestinal
      tract with pulmonary and placental metastases. CONCLUSION: The biologic course of
      malignancies in pregnancy is complex. In gastrointestinal cancer, normal
      pregnancy symptoms can mask and delay the diagnosis. As in this patient, very
      rare presentations are possible.

PMID- 12063885
TI  - Investigation of GPOs yields mixed opinions.

PMID- 12063886
TI  - Pittsburgh hospitals band together to reduce medication errors.

PMID- 12063884
TI  - Successful conservative treatment for advanced interstitial pregnancy. A case
      report.
AB  - BACKGROUND: Interstitial pregnancy is a relatively rare and life-threatening
      disease, occurring in 2-4% of all extrauterine pregnancies, and the maternal
      mortality rate is 2-2.5%. Laparoscopic surgery and, less commonly, methotrexate
      are the treatments of choice for interstitial pregnancy. However, there is
      another treatment, ultrasound-guided direct injection of etoposide, the effect
      and safety of which are unclear. CASE REPORT: In a 32-year-old woman with
      interstitial pregnancy at 12 weeks of gestation, ultrasound-guided direct
      injection of etoposide (100 mg) was used successfully after intravenous high-dose
      methotrexate, 300 mg (200 mg/m2), therapy failed to produce a response. The
      patient's posttherapeutic course was smooth. Twelve months after treatment, she
      conceived and later delivered a healthy infant vaginally without adverse events.
      CONCLUSION: Ultrasound-guided direct injection of etoposide offers another choice
      for treating advanced interstitial pregnancy, but further study is needed to
      define its efficacy and safety.

PMID- 12063887
TI  - Safety analyses take on engineer's perspective at JCAHO's urging.

PMID- 12063888
TI  - USP issues standards for unit dose repackaging.

PMID- 12063889
TI  - CDC wants October's influenza vaccine reserved for most-needy patients.

PMID- 12063890
TI  - Ensuring continuity of care and accuracy of patients' medication history on
      hospital admission.

PMID- 12063891
TI  - Summary of the second executive session on emergency preparedness and the
      pharmaceutical supply chain.

PMID- 12063892
TI  - Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride,
      and gamma-hydroxybutyrate.
AB  - The abuse of methylenedioxymethamphetamine (MDMA), flunitrazepam, ketamine
      hydrochloride, and gamma-hydroxybutyrate (GHB) is discussed. Club drugs are
      chemical substances used recreationally in social settings. Use is increasingly
      frequent among young people, especially during all-night dance parties. All four
      agents have been classified as controlled substances. MDMA ("ecstasy") is
      available as a tablet, a capsule, and a powder; formulations may contain many
      adulterants. MDMA increases the release of neurotransmitters. The desired effects
      are euphoria, a feeling of intimacy, altered visual perception, enhanced libido,
      and increased energy. The most common adverse effects are agitation, anxiety,
      tachycardia, and hypertension. More serious adverse effects include arrhythmias,
      hyperthermia, and rhabdomyolysis. Flunitrazepam is a potent benzodiazepine. At
      higher doses, the drug can cause lack of muscle control and loss of
      consciousness. Other adverse effects are hypotension, dizziness, confusion, and
      occasional aggression. Ketamine is a dissociative anesthetic used primarily in
      veterinary practice. It may be injected, swallowed, snorted, or smoked. Like
      phencyclidine, ketamine interacts with the N-methyl-D-aspartate channel.
      Analgesic effects occur at lower doses and amnestic effects at higher doses.
      Cardiovascular and respiratory toxicity may occur, as well as confusion,
      hostility, and delirium. GHB, a naturally occurring fatty acid derivative of
      gamma-aminobutyric acid, was introduced as a dietary supplement. Increasing doses
      progressively produce amnesia, drowsiness, dizziness, euphoria, seizures, coma,
      and death. Flunitrazepam, ketamine, and GHB have been used to facilitate sexual
      assault. Supportive care is indicated for most cases of club drug intoxication.
      The increasing abuse of MDMA, flunitrazepam, ketamine hydrochloride, and GHB,
      particularly by young people in social settings such as clubs, should put health
      care professionals on guard to recognize and manage serious reactions.

PMID- 12063893
TI  - Implementation of a therapeutic-interchange clinic for HMG-CoA reductase
      inhibitors.
AB  - A therapeutic-interchange clinic for statins is described. In 1999, the
      Department of Defense mandated the use of cerivastatin and simvastatin as the
      formulary statins in all military health care facilities by April 2000.
      Cerivastatin was the preferred agent; the goal was to use this agent in 60-65% of
      all patients. Walter Reed Army Medical Center developed a voluntary therapeutic
      interchange clinic for patients receiving statins. Goals included facilitating
      the rapid switching of patients to the formulary statins, maximizing the use of
      the preferred agent, maintaining or improving lipid control, monitoring safety,
      determining costs, educating patients about their treatment, and documenting
      satisfaction with the clinic. Written educational materials were prepared, an
      algorithm for statin conversion was created, and laboratory tests were performed,
      among other measures. Between January and April 2000, 1356 patients were seen by
      the therapeutic-interchange clinic; of these, 942 agreed to have the efficacy and
      safety of their therapy monitored by the clinic. Before the formulary change, the
      most commonly prescribed statins were atorvastatin (44% of patients) and
      pravastatin (42%). Under the conversion policy, 96% of patients received
      cerivastatin and 4% simvastatin. The percentage of patients achieving their
      targeted low-density-lipoprotein cholesterol concentration increased from 65% to
      75%. The policy saved an average of $115 per patient in the first year. Most
      patients were satisfied with the clinic, but only 36% of providers were
      satisfied. Cerivastatin was withdrawn from the market in August 2001; simvastatin
      became the only formulary statin. A therapeutic-interchange clinic at a military
      medical center provided an efficient means of switching a large number of
      patients to alternative statin therapy, monitoring the outcomes, and
      individualizing patient care.

PMID- 12063894
TI  - Perceptions of quality and value in state and local pharmacy professional
      organizations.
AB  - Officer and member perceptions of the quality and value of the services provided
      by American Society of Health-System Pharmacists (ASHP) state affiliates and
      local chapters were studied. A survey was mailed in December 2000 to all 249
      state society and local-chapter officers in Ohio, Pennsylvania, New York,
      Minnesota, and Illinois and a random sample of 1191 members. The survey solicited
      ratings of the quality and value of programs and services related to continuing
      education, communications, community service, and membership benefits. Of 1440
      surveys mailed, 26 were returned as undeliverable; 308 were returned in usable
      form, for a total response rate of 22%. The most frequent job categories were
      hospital staff pharmacist (n = 74), hospital pharmacy manager (n = 66), and
      hospital clinical pharmacist (n = 49). Overall, members perceived lower quality
      than officers in clinical and administrative continuing-education programs
      offered by their local chapters. Members also perceived less value in
      administrative continuing-education programs than did officers. Member and
      officer perceptions were similar in the areas of communication and community
      services. Neither members nor officers appeared to value social functions highly
      as a membership benefit. A survey of state and local affiliates of ASHP in five
      states identified several areas where officers and members had different
      perceptions of the quality and value of services provided by these organizations.

PMID- 12063895
TI  - Perceived importance and self-assessment of the skills of Canada's health-system
      pharmacy managers.
AB  - The relationship between the perceived importance of managerial skills and self
      assessed proficiency in each skill among health-system pharmacy managers in
      Canada was examined, and the demographic characteristics associated with pharmacy
      managers who lack these skills were analyzed. Surveys were mailed to 514 health
      system pharmacy managers in Canada in July 2000. The survey listed 61 specific
      managerial skills, under seven general categories. The respondents were asked to
      rate the level of importance that each of the skills had in their job and rate
      their proficiency in each skill. Ratings were based on a five-point Likert scale
      ranging from very high importance or skill level to very low importance or skill
      level. The response rate was 52.7%. Of the 61 specific managerial skills
      considered, the majority of respondents identified "Demonstrating ethical
      conduct" as both the most important skill and their greatest strength.
      "Understand the operating principles of managed care" was viewed as the least
      important skill, while "Participating in the implementation of a marketing
      program" was respondents' greatest weakness. There were significant differences
      in the mean self-assessed skill levels of the respondents according to their
      educational background, size of the institution in which they work, and years of
      managerial experience. Health-system pharmacy managers with a master of business
      administration degree had a significantly higher overall mean perceived skill
      level than managers in all other "Education" categories. Managers with a bachelor
      of science degree in pharmacy had a significantly lower overall mean perceived
      skill level than those with a bachelor of science degree in pharmacy plus "other"
      degrees, while managers employed in institutions of 500 or more inpatient beds
      had a significantly higher overall self-rated mean skill level than managers
      employed in institutions of 51-100 inpatient beds. A national survey of health
      system pharmacy managers in Canada revealed a pressing need for better training
      in managerial skills for these pharmacists.

PMID- 12063896
TI  - Implementing a performance evaluation system in a correctional managed care
      pharmacy.
AB  - The development and implementation of a departmental performance evaluation
      system for a correctional managed care pharmacy are described. Health care
      services for approximately 150,000 offenders within the Texas Department of
      Criminal Justice are provided through an arrangement with two university systems,
      the University of Texas Medical Branch (UTMB) and Texas Tech University Health
      Sciences Center. UTMB provides all distributive pharmacy services through a
      central pharmacy located in Huntsville, Texas. The pharmacy department
      distributes 9,000-15,000 medication orders daily to over 140 facilities. Each
      department within UTMB Correctional Managed Care is evaluated against
      predetermined quality indicators. This evaluation system is collectively called
      the operational performance evaluation system (OPES) and is used, in part, to
      determine pay-for-performance eligibility. Before fiscal year 2001, pharmacy
      distributive services were provided under a third university system. Joining the
      UTMB system required the pharmacy department to not only participate in OPES but
      to develop quality indicators and measurement systems to evaluate departmental
      performance. Indicators were chosen to reflect a commitment to quality while
      assuring appropriate productivity in the provision of pharmaceutical care. Seven
      pharmaceutical care quality indicators were chosen and weighted by perceived
      importance. A system for data collection, measurement, and reporting was also
      developed. Implementation of a departmental performance evaluation system
      provides a means to measure service quality, identify areas of weakness, track
      performance over time, and lower costs. By setting concrete goals, this system
      raises awareness and promotes interdependence among department personnel.

PMID- 12063897
TI  - Use of drug manufacturers' patient assistance programs by safety net providers.

PMID- 12063898
TI  - Manufacturer warnings of system-related medication errors.

PMID- 12063899
TI  - Direct care workers--number one quality indicator in long-term care. A consumer's
      perspective.

PMID- 12063900
TI  - Who do we want to care for our mothers? Defining and reinforcing the direct care
      workforce.

PMID- 12063901
TI  - The crisis in long-term care. Finding and retaining our direct care workers.

PMID- 12063902
TI  - The Board of Nursing and the regulation of nurse aides in NC.

PMID- 12063903
TI  - A perspective on frontline staffing.

PMID- 12063904
TI  - Direct care workers. Reinforcing the numbers, reinforcing commitment.

PMID- 12063905
TI  - Access to care.

PMID- 12063906
TI  - Access to care.

PMID- 12063907
TI  - The evolution of American medicine and the Duke Endowment Health Care (Hospital)
      Division since 1924.

PMID- 12063908
TI  - Premenstrual dysphoric disorder. A guide for the treating clinician.
AB  - Up to 75% of women report some premenstrual symptoms, but less than 10% have
      symptoms severe enough to qualify for a diagnosis of PMDD. A key to diagnosis is
      establishing a pattern of typical PMDD symptoms that recur during the late luteal
      phase of the menstrual cycle and remit after menses. Underlying psychiatric and
      medical disorders that might mimic PMDD should be ruled out or addressed. The
      clinician should recognize that severe PMS and PMDD are most likely caused by
      sensitivity to hormonal cycling rather than an abnormality of hormone levels.
      Current treatment is based on the hypothesis that serotonin depletion is
      responsible for the premenstrual irritability, dysphoria, and poor impulse
      control in PMDD. There is some evidence that GABA, endogenous opiates,
      allopregenolone, and various vitamins and minerals might play roles in severe PMS
      and PMDD. Treatment with oral contraceptives or supplementary progesterone or
      estrogen has not been effective. For the treating clinician, a reasonable
      approach to the patient with severe PMS or PMDD is shown in Table 2.

PMID- 12063909
TI  - Enhanced surveillance of maternal mortality in North Carolina.

PMID- 12063910
TI  - A long-term care plan for North Carolina. Synopsis of the North Carolina
      Institute of Medicine final report.

PMID- 12063911
TI  - The direct care workforce crisis in long-term care.

PMID- 12063912
TI  - [Trends in individualizing therapy of stomach carcinoma].

PMID- 12063913
TI  - [Influence of laparoscopic staging on therapy of stomach carcinoma].
AB  - Surgical staging is the gold standard in assessing the extent of disease in
      gastric cancer. The introduction of video-assisted laparoscopy has allowed the
      surgeon the opportunity to maintain high quality with low morbidity and reduced
      length of stay for the patient. The body of evidence supporting its use in
      routine staging of gastric cancer is significant and now the potential to expand
      the role of laparoscopy into the area of new therapeutic procedures can be
      explored.

PMID- 12063914
TI  - [Is neoadjuvant therapy for locally advanced stomach carcinoma standard?].
AB  - Despite surgical efforts and encouraging data of a few postoperative therapy
      trials, locally advanced gastric cancer is in need of the development of
      effective multimodal therapeutic concepts. Regarding preoperative therapy the
      goal is to raise the number of complete tumor resections (R0-resections) leading
      to an improved prognosis of the disease. Neoadjuvant therapy has the theoretical
      advantage of early destruction of distant micrometastasis with a consecutive
      reduction of tumor relapse outside the resection margins. The likelihood of R0
      resections should be increased with the response of the primary tumor to
      neoadjuvant therapy. Neoadjuvant chemotherapy using platinum based regimens in
      gastric cancer has shown its activity in a number of phase II studies. Especially
      after response to chemotherapy the survival was significantly better after
      complete surgical tumor resection. The neoadjuvant use of a sequence of
      chemotherapy followed by radiotherapy before gastrectomy did result in a complete
      histopathological response in 20-25% of gastric cancer patients. This regimen
      seems to be promising, but there are still no long term results available.
      Parallel to the expected data from the first phase III studies the main impact of
      research in this field has to be focused on to the development of new and
      effective therapeutic agents and with accompanying identification of factors
      which are able to predict the response to neoadjuvant treatment.

PMID- 12063915
TI  - [Extent of resection in surgery of stomach carcinoma].
AB  - The extraluminal extent of resection in cases of advanced gastric cancer is
      controversial. If, however, following meticulous staging--including the detection
      of free abdominal tumor cells--complete resection seems possible, then
      multivisceral resection is justified. If complete resection is achieved, the
      prognosis of these patients can be improved. Left pancreatic resection should be
      performed only if the tumor invades the pancreas directly. Splenectomy is
      indicated if the tumor invades the organ directly or if there are locally
      advanced tumors of the proximal third of the stomach and tumors of the esophageal
      gastric junction. However, it has to be kept in mind that splenectomy is an
      independent negative prognostic factor. The extent of lymphadenectomy (LA) in
      gastric cancer is still under discussion. According to the 10-year results of the
      Dutch Gastric Cancer Study, there might be subgroups which have a survival
      benefit after extended (D2) LA. These include, as the German Gastric Cancer Study
      corroborated, patients with very early stage II and stage IIIa lymph node
      metastases. As neither of these stages can at present be diagnosed before or
      during surgery, D2 lymphadenectomy should be the standard procedure for all
      patients with gastric cancer. Recent studies have shown that it might be possible
      with the help of the Sentinel Node Technique to individualize lymphadenectomy in
      locally gastric cancer as well. The beneficial effects of adjuvant chemoradiation
      in gastric cancer do not mean, however, that the extent of resection may be
      reduced. Adjuvant chemoradiation following complete resection and D2
      lymphadenectomy should still not be regarded as standard therapy.

PMID- 12063916
TI  - [Postoperative adjuvant chemoradiotherapy in high risk stomach carcinoma].
AB  - Gastric cancer is a common cancer worldwide with a high mortality rate. Despite
      curative intent resection, locoregional failure as a frequent site of recurrence
      is responsible in part for this high mortality. Many attempts have been made to
      decrease the risk of recurrence after resection. Studies involving postoperative
      chemotherapy as a single modality have not clearly demonstrated benefit.
      Similarly, most studies of postoperative radiation therapy have not clearly shown
      an improvement in overall survival. Recently, however, a USA Intergroup study
      indicated a survival advantage for chemoradiation therapy compared to surgery
      alone for patients with locally advanced gastric cancer. "Intergroup-116" is a
      large-scale randomized trial designed to evaluate the role of adjuvant
      chemotherapy plus radiotherapy following curative intent gastric resection. The
      data from this study demonstrate a survival benefit with adjuvant chemoradiation
      that may in large part be due to better locoregional control. While many patients
      had a less then adequate lymph node dissection, survival was not associated with
      the type of lymph node dissection performed. Toxicity was acceptable. "Intergroup
      116" indicates that postoperative chemoradiation should be considered as a
      standard care option for patients with locally advanced gastric cancer. Future
      studies should evaluate potentially more effective systemic therapy, molecularly
      directed treatment, and possibly, whether or not more formal lymph node
      dissections would obviate the need for radiation.

PMID- 12063917
TI  - [Neuroendocrine tumors of the stomach. Surgery therapy and prognosis].
AB  - Gastric carcinoid tumors are rare lesions characterized by hypergastrinemia that
      arise from enterochromaffin-like (ECL) cells of the stomach. A classification
      system distinguishing three types of gastric carcinoid tumors has been proposed:
      1) tumors related to chronic atrophic gastritis, 2) tumors associated with
      Zollinger-Ellison syndrome, and 3) sporadic lesions. It is apparent that
      hypergastrinemia-associated gastric carcinoids show a rather benign biological
      behavior. Normo-gastrinemic sporadic lesions, on the other hand, require an
      aggressive surgical management. We report seven patients with gastric
      neuroendocrine tumors ("carcinoids"), who underwent surgical treatment in our
      department between 1988 and 2000. Surgical therapy included total gastrectomy
      with D2 lymphadenectomy in two cases with type I tumors and for one patient with
      type III tumor. One patient with a type II tumor was treated by distal subtotal
      gastrectomy and another by antrectomy. A local excision was performed on one
      patient with type I tumor. After a mean follow-up of 8 years, 5 of 7 patients are
      alive without recurrence.

PMID- 12063918
TI  - [D3 versus D2 dissection in stomach carcinoma. A case-control study of
      postoperative morbidity, survival and early oncologic outcome].
AB  - INTRODUCTION: In western countries, the benefit of the Japanese extended D3 lymph
      node dissection in gastric cancer patients who have been operated on in curative
      intent has not been proven and higher rates of side effects are expected. The
      present matched-pair study retrospectively compared the new D3 method (1995-1999)
      with the historic D2 dissection (1982-1995). METHODS: Two 1:1 matched-pair
      populations were created: (1) regarding intra- and postoperative course,
      morbidity and mortality, 2 x 67 patients stratified to "age", "gender", "surgical
      procedure", "splenectomy" and "extended resections"; and (2) regarding early
      oncologic outcome, 2 x 32 patients additionally stratified to "UICC-stage" and
      "Lauren-classification". The D3 dissection was performed according to the
      Japanese method without routine pancreaticosplenectomy. RESULTS: D3 dissection
      harvested significantly (P = 0.004) more lymph nodes per patient: 56.4 vs. 46.8.
      Postoperative mortality was 3% (n = 2) in both groups, the overall complication
      rate of 30% (D3) vs. 25% (D2) was equivalent (P = 0.678) and the rate of surgical
      complications was identical (21%). Non-surgical complications of 21% after D3
      dissection were not significantly elevated (vs. 10%; P = 0.143). Operative time
      [289 min (D3) vs. 218 min (D2); P = 0.0001] and postoperative stay [17.4 days
      (D3) vs. 14.5 days (D2); P = 0.003] were significantly longer after the extended
      procedure. The were no statistically significant differences between 2-year
      overall survival, locoregional-, distant- and overall recurrence-free survival.
      CONCLUSIONS: Compared to the D2 method, D3 dissection is feasible without
      disadvantages in the patients. However, D3 dissection cannot routinely be
      recommended because--possibly due to the short follow-up period and the small
      number of patients so far observed--an oncologic benefit could not be shown.

PMID- 12063919
TI  - [Structural anomalies in lung apices after pneumothorax operation].
AB  - INTRODUCTION: Fifty-eight patients (mean age 27 years, range 17-44) with primary
      spontaneous pneumothorax (PSP) underwent resection of apical bullae and partial
      apical pleurectomy via mini-thoracotomy or thoracoscopy, in 12 cases bilaterally,
      between 1982 and 1999. METHOD: After a mean follow-up period of 111 (16-212)
      months, 26 patients with 31 operated lungs were reassessed by high-resolution CT
      (HRCT) to demonstrate postoperative morphological changes. RESULTS: Neither
      relevant clinical symptoms nor recurrence of a pneumothorax were found. However,
      HRCT revealed new apical bleb formations in 22 (71%) of 31 lungs. Neither the
      surgical approach, the technique of resection nor giving up smoking could be
      correlated to the tissue alterations. Surgical excision of the apex of the lung
      does not stop bleb formation. CONCLUSION: This study confirms earlier results
      from a different institution, when blebs recurred in 50% of the cases. The
      presence of these new apical formations neither influenced the clinical outcome
      nor predisposed to recurrence of PSP. Parietal (partial) pleurectomy seems
      mandatory to prevent PSP in the long-term.

PMID- 12063921
TI  - [Airlimb. Initial experiences with a new immediate early management prosthesis
      with individually adjustable air chambers].
AB  - Amputations of the lower extremity are still a common problem in diabetic feet
      and peripheral vasculopathies. The presented paper introduces a new device for an
      easier and faster mobilization of below-the-knee amputees. It is based on a new
      modular prostheses with individual inflatable air bladders. The compliance rate
      is higher with this device and it could be used from the day of surgery until the
      definitive prostheses is made. A biomechanical cadaver study with the prostheses
      will also be presented.

PMID- 12063920
TI  - [The open lung concept. Clinical application in severe thoracic trauma].
AB  - INTRODUCTION: The pathomorphological substratum of the pulmonary contusion is a
      parenchymatous hemorrhage followed by interstitial and alveolar edema, finally
      resulting in a severe damage of the surfactant system. The pathophysiological
      consequence is an imbalance between ventilation and perfusion, which causes the
      clinical finding of hypoxia. METHODS: Between December 1997 and December 2000, we
      treated 32 polytraumatized patients (ISS 43, PTS 32) additionally suffering from
      severe chest contusion (AIS 5, PTST 14), by ventilation according to the Open
      Lung Concept (OLC). The initial disturbance of oxygenation was shown by a mean
      paO2/FIO2-ratio of 134 (96;181) mmHg. The OLC recruits atelectatic lung areas by
      the application of a defined temporary positive inspiratory pressure (PIP), which
      is called the "opening pressure". The recruited lung areas were kept open by high
      total-PEEP. RESULTS: For the recruitment procedure, a mean PIP of 65 (51;65) mbar
      was required. Recruited alveoli were kept open by a total-PEEP of 22 (20;23)
      mbar. The paO2/FIO2-ratio increased significantly (P < 0.001) from 134 (96;181)
      to 522 (433;587) mmHg. After the recruitment procedure, we could reduce PIP and
      FIO2. In spite of the minimal tidal volumes of 3.5 (3.0;3.9) ml per kg bodyweight
      by which our patients were ventilated, the levels of oxygenation and normocapnia
      could be maintained. There were no evidences for side-effects like perfusion
      impairment. Two patients (6.25%) died of extrapulmonary causes. CONCLUSION:
      Ventilation according to the OLC seems to be a highly effective treatment of
      ventilation-perfusion-impairment following pulmonary contusion. Minimal tidal
      volumes and the low PIP-levels after the recruitment procedure meet the demands
      of a lung-protective Low-Tidalvolume-Ventilation.

PMID- 12063922
TI  - [Muir-Torre syndrome].
AB  - The Muir-Torre syndrome (MTS) is an autosomal dominant disease defined by the
      coincidence of at least one sebaceous skin tumor and one internal malignancy. We
      describe an additional case and give a review of the literature. Over a period of
      7 years, 19 skin tumors were excised in a 50 year old male patient. A total of 3
      colonic carcinomas, one gastric carcinoma and one laryngeal carcinoma were
      operated successfully. The underlying defective mutation in the hMSH2 gene and
      the microsatellite instability were demonstrable. MTS is graded as a subgroup of
      hereditary non-polyposis colorectal cancer (HNPCC). In patients with MTS and with
      family members with known defective mutation, regular follow-up and search for
      new malignancies are mandatory.

PMID- 12063923
TI  - [Malignant transformation of perianal Buschke-Lowenstein tumor. Extensive
      abdominoperineal rectum excision and reconstruction with transpelvic myocutaneous
      rectus abdominis muscle flap].
AB  - INTRODUCTION: The Buschke Lowenstein tumor (giant condyloma) in its perianal
      variant is an extremely rare disease caused by human papilloma virus. Although of
      histologically benign appearance, it infiltrates and destroys the surrounding
      tissue. There is a high risk of local recurrence and malignant transformation.
      The treatment of choice is wide surgical resection. CASE: A 56-year-old woman
      presented with perianal giant condyloma infiltrating the rectum and vagina. The
      extensive soft tissue defect resulting from wide resection was filled with a
      transpelvic myocutaneous rectus abdominis flap. Histology showed a squamous cell
      carcinoma arising in the Buschke Lowenstein tumor with clear resection margins.
      Therefore, the patient was irradiated locally after uneventful primary wound
      healing. CONCLUSION: A simultaneous reconstruction of a large pelvinoperineal
      soft tissue defect with the transpelvic myocutaneous rectus abdominis flap allows
      primary healing, accelerated rehabilitation, and safe adjuvant radiotherapy
      without risk of serious radiation damage to the small bowel by preventing it from
      protruding into the pelvic defect.

PMID- 12063924
TI  - [Reliable and unreliable health measures in surgery].
AB  - Despite high standards in theatre design, surgical skills and antibiotic
      prophylaxis, surgical site infections are still a major complication in modern
      surgery. After urinary tract infections and lower respiratory tract infections
      they account for 15.8% of all nosocomial infections in Germany [31]. Causes are
      multiple and only partially exogenous. The single most important (exogenous) risk
      factor is the technical skill of the surgeon. Not all surgical site infections
      are therefore preventable by infection control measures alone. Useful and useless
      infection control measures will be evaluated critically in the following review
      according to data in the literature.

PMID- 12063925
TI  - [Massive pulmonary capillary occlusion by microthrombi. Unexpected cause of fatal
      right heart failure during liver transplantation].
AB  - We report the case of a 46-year old man who developed an unexpected fatal cardiac
      failure during liver transplantation. Attempts at resuscitation were
      unsuccessful. At necropsy the lungs showed numerous microthrombi occluding small
      lung vessels and pulmonary capillaries. Thrombi were not found in other organs.
      The source of this extensive thrombus formation is not known. The thrombi could
      have been developed within the liver, the venous blood stream between liver and
      lungs or the pulmonary capillaries. In our experience, this complication is very
      rare, and a risk profile is not known.

PMID- 12063926
TI  - [Massive localized lymphedema in an extremely obese patient].
AB  - Soft tissue tumors are commonly encountered in all surgical departments. The
      authors present a case of a very rare large tumor lesion, with macroscopic signs
      of liposarcoma.

PMID- 12063927
TI  - [Wound management with coconut oil in Indonesian folk medicine].
AB  - The medical plants which are used to treat wounds and injuries by the ethnic
      group of Ngada on Flores, an Eastern Indonesian island, will be presented.
      Additionally, the coconut oil used to treat wounds and to conserve medicinal
      plants will be analysed biochemically. The people of Ngada use the following
      plants for wound treatment: seeds of the betel nut (Areca catechu L.), fruits of
      papaya (Carica papaya L.), leaves of the Indian Hydrocotyle (Centelle asiatica
      L.), the rhizome of turmeric (Curcuma domestica Val. and Curcumara xanthorrhiza
      Roxb.), leaves of betel (Piper betel L.). Coconut oil is particularly useful
      because of its biochemical structure: unlike olive oil and animal fatty tissue,
      it consists of short-chained and saturated fatty acids. These qualities in
      coconut oil prevent it from becoming oxidized and rancid, thus making it suitable
      for the preservation of medicinal plants and for wound treatment.

PMID- 12063928
TI  - [Anastomosis dehiscence in the gastrointestinal tract. Diagnosis and therapy].

PMID- 12063929
TI  - [Medical classification in the DRG system. 2 Procedural key OPS-301 version 2.1].

PMID- 12063931
TI  - [Physician confidentiality responsibility regarding communicable diseases at
      patient admission of acute or chronic patients to hospitals or nursing homes].

PMID- 12063930
TI  - [Kidney transplantation case example].

PMID- 12063932
TI  - [Anastomosis dehiscence in the gastrointestinal tract].

PMID- 12063933
TI  - [Joint position of the Professional Society of German Surgeons and the
      Professional Society of German Anesthetists. Perioperative performance in
      anesthesia and surgery].

PMID- 12063934
TI  - Nurses making a difference one life at a time.

PMID- 12063935
TI  - AORN Guidance Statement--safe medication practices in perioperative practice
      settings.

PMID- 12063936
TI  - Wake-up call--standardization is crucial to eliminating medication errors.

PMID- 12063938
TI  - Limited-English patients.

PMID- 12063937
TI  - Harmonizing to form a rainbow of power and accomplishments.

PMID- 12063939
TI  - Reprocessing single use devices.

PMID- 12063942
TI  - Preoperative hair removal--a systematic literature review.
AB  - This article describes a systematic literature review on whether, how, and when
      to perform preoperative hair removal. By searching electronic databases and
      reference lists of relevant articles, team members identified 20 clinical studies
      that deal with preoperative hair removal. No strong evidence was found to
      advocate against preoperative hair removal. Furthermore, there was strong
      evidence to recommend that when hair removal is considered necessary, shaving
      should not be performed. Instead a depilatory or electric clipping, preferably
      immediately before surgery, should be used.

PMID- 12063943
TI  - Ethics in perioperative practice--patient advocacy.
AB  - Though often difficult, ethical decision making is necessary when caring for
      surgical patients. Perioperative nurses have to recognize ethical dilemmas and be
      prepared to take action based on the ethical code outlined in the American Nurses
      Association's (ANA's) Code of Ethics for Nurses with Interpretive Statements. In
      this second of a nine-part series that will help perioperative nurses relate the
      ANA code to their own area of practice, the author looks at the third provision
      statement, which addresses nurses' position as patient advocates.

PMID- 12063944
TI  - Mentoring--what it is and how to make it work.
AB  - Mentors are people who help those less experienced in their field learn about the
      field and advance their careers. Mentors not only help mentees learn, they also
      learn from the mentor-mentee relationship. To be effective, mentors should
      possess patience, enthusiasm, knowledge, a sense of humor, and respect. They also
      should advocate for mentees and get to know them, thus allowing mentees to
      succeed and the mentor-learner relationship to grow.

PMID- 12063945
TI  - Outpatient laparoscopic Nissen fundoplication.
AB  - Gastroesophageal reflux disease affects more than 40% of Americans, causing
      heartburn and reflux of gastric contents into the esophagus when bending or lying
      down. Lifestyle modification, such as weight loss and a diet rich in protein and
      low in fat and glucose, should increase the patient's resting lower esophageal
      sphincter pressure. Avoiding exacerbating substances, such as mint, chocolate,
      alcohol, and tobacco, also may reduce symptoms. Medications may be prescribed to
      reduce persistent symptoms, although no medication currently available cures the
      disease process. Patients who need antireflux medication regularly for four to
      six weeks or more may be candidates for laparoscopic Nissen fundoplication.
      Patients who do not want to take antireflux medication for the rest of their
      lives, cannot afford the medication for an extended period of time, or suffer
      significant side effects from the medication also are candidates. This article
      describes performing Nissen fundoplication laparoscopically on an outpatient
      basis. The average length of hospital stay has been decreased to two to three
      hours when performed laparoscopically on an outpatient basis from 10 days for the
      open procedure and two to three days when performed laparoscopically on an
      inpatient basis. The incidence of recurrent heartburn is less than 2% when the
      procedure is performed laparoscopically and does not appear to be clinically
      significant.

PMID- 12063946
TI  - Reprocessing single-use devices--the ethical dilemma.
AB  - This is the first in a series of three articles about reprocessing medical
      devices labeled as "single use" by the manufacturer. The goal of reprocessing
      single-use devices (SUDs) is to save money and decrease environmental pollution.
      Reprocessing can be performed on SUDs that have been used on other patients or
      opened but not used. The practice of reprocessing is complex and technical, and
      it raises concerns about patient safety, ethics, the environment, and costs.
      Opponents of reprocessing argue that the risks outweigh the benefits and that
      research has not proven it to be safe. Supporters believe the devices are labeled
      for single use so that manufacturers can maintain their profit margin and avoid
      liability. The purpose of part one of this article is to inform nurses about the
      ethical issues, patient safety issues (e.g., infection control, patient injury),
      and previously performed research studies regarding reprocessing and reusing
      products that are intended for single use. The second and third articles in this
      series will discuss procedures for reprocessing, roles of the regulatory agencies
      involved, and advantages and disadvantages of using third-party reprocessors.

PMID- 12063947
TI  - Free breathing magnetic resonance cholangiopancreatography (MRCP) at end
      expiration: a new technique to expand clinical application.
AB  - BACKGROUND/AIMS: To develop a new magnetic resonance cholangiopancreatography
      technique for patients who cannot hold their breath or breathe regularly and fail
      to be successfully examined with conventional magnetic resonance
      cholangiopancreatography methods. METHODOLOGY: Within a one-year period, 15
      patients including 6 children and 9 adults were studied. Magnetic resonance
      cholangiopancreatography was performed in a 1.5 Tesla GE MR scanner with
      capability of single-shot fast spin echo sequence. In all patients except for the
      children, magnetic resonance cholangiopancreatography was attempted with the
      breathhold technique at first. However, this failed in some due either to the
      patients being too old or too weak to hold their breath long enough for single
      shot fast spin echo sequence, which usually took about 20-30 seconds for the
      complete scanning. These 15 cases were then scanned slice-by-slice in operator's
      control mode by monitoring patient's respiratory pattern from the TV monitor.
      Scanning was started near the end of patient's expiration. This technique was
      performed after we had carefully decided the baseline of each patient's
      respiration cycle. Each slice was scanned at an interval depending on the
      patient's respiratory frequency. It was acquired at an interval of two
      respiratory cycles for each sequential slice when the patient's respiration
      frequency was around 10-15 cycles per minute, at three cycles when respiration
      frequency was around 15-20, at four cycles when the frequency was around 20-25,
      and at an interval of 5 cycles when it was above 25. The acquired source images
      were then reconstructed for a 3D image. RESULTS: Magnetic resonance
      cholangiopancreatography of good image quality was obtained in all of these
      fifteen patients. Each set of images took about 2-3 minutes. No marked artifact
      was found. The reconstructed 3D image also afforded satisfactory quality for
      evaluation of both normal ductal anatomy and lesions of the biliary-pancreatic
      system. The axial single-shot fast spin echo sequence images of the liver and
      pancreas were also successfully obtained with this method. Magnetic resonance
      cholangiopancreatography findings in these 15 patients included type I
      choledochal cyst (n = 4), dilatation of the intrahepatic bile ducts due to mass
      compression (n = 3, one Klatskin tumor and two hilar masses), pancreatic
      carcinoma (n = 1), acute cholecystitis without biliary tract dilatation (n = 1),
      acute pancreatitis with mild biliary dilatation and non-visible pancreatic duct
      (n = 1), dilatation of biliary tract without definite lesions (n = 2), common
      hepatic duct obstruction (n = 1), and normal biliary and pancreatic duct without
      dilatation or lesions (n = 2). CONCLUSIONS: Free breathing magnetic resonance
      cholangiopancreatography technique is very useful for patients in whom
      conventional methods cannot be successfully undertaken. It affords informative
      images that are comparable to other magnetic resonance methods.

PMID- 12063948
TI  - Practical usefulness of bipolar scissors in hepatectomy.
AB  - BACKGROUND/AIMS: Because less surgical stress might preserve quality of life of
      patients, it is more desirable to decrease both intraoperative blood loss and
      liver injury especially in hepatectomy. For the patients with hepatocellular
      carcinoma based on chronic liver dysfunction, it is more essential to control
      bleeding and reduce liver injury in hepatectomy than in other diseases. In the
      present study, a retrospective comparison about usefulness was made in
      hepatectomy between using bipolar scissors and using conventional procedure.
      Before 1997, in our hospital, we had dissected the liver by using the crushing
      clamp method in combination with cauterization by microwave coagulator for the
      purpose of reducing intraoperative blood loss. Since 1998, bipolar scissors have
      been introduced toward hepatectomy as a new, simple and easy device to use.
      METHODOLOGY: Fifty-three consecutive patients with primary hepatocellular
      carcinoma at TNM stage I/II who underwent partial hepatectomy between 1996 and
      1999 were enrolled in the study. Thirty-two patients (1996-1997) were treated by
      using a conventional method (group CM) and 21 patients (1998-1999) were treated
      by using bipolar scissors (group BS). The factors related to surgical stress were
      compared between the two groups. RESULTS: The amounts of blood loss/transfusion
      were lower in group BS (641/100 mL) than in group CM (1112/450 mL). The
      percentages of patients who lost more than 1000 mL of blood were lower in group
      BS (19%) than in group CM (47%) (P = 0.04). An intraabdominal drainage was needed
      for 9.0 +/- 6.6 days in group BS, and the drainage period was shorter than that
      in group CM (15.0 +/- 8.7 days) (P = 0.01). CONCLUSIONS: These results indicated
      the superiority of bipolar scissors in decreasing blood loss and liver injury to
      the conventional method, suggesting the worth of performing the prospective
      randomized study.

PMID- 12063949
TI  - Is it possible with an immunophenotypic study to foresee the oncologic risk of
      epithelial gastric dysplasia?
AB  - BACKGROUND/AIMS: Epithelial gastric dysplasia is considered the only true marker
      of gastric cancer. High-grade dysplasia is a surgical therapy needing lesion and
      low-grade dysplasia is considered a lesion with a low oncologic risk. The aim of
      this experience was to verify whether there are any immunohistochemical
      evaluations which may enable one to foresee more precisely the evolution of
      epithelial gastric dysplasia. METHODOLOGY: Immunophenotypic evaluation was
      effected in 70 cases of low-grade dysplasia (41 males, average age: 57.4) and in
      50 cases of high-grade dysplasia (31 males, average age: 58). These cases were
      retrospectively selected and the studied samples are represented by gastric
      biopsies obtained in the course of endoscopy performed for dyspepsia. Epithelial
      gastric dysplasia diagnosis was done according to Goldstein and Lewin and the
      clinical subdivision was effected using the criteria of Rugge et al. Four
      antigens were studied using Abs against pepsinogen C, gastric foveolar M1,
      intestinal CAR-5 and pancreatic DU-PAN-2 Ags. RESULTS: Epithelial gastric
      dysplasia is characterized by a progressive reduction of gastric markers with a
      progressive expression of enteropancreatic antigens. Low-grade dysplasia is
      characterized by a frequent gastro-enteropancreatic coexpression, and high-grade
      dysplasia by a frequent enteropancreatic coexpression or by no markers
      expression. Low-grade dysplasia with greater enteropancreatic markers progresses
      frequently towards gastric cancer; high-grade dysplasia with enteropancreatic
      markers only is associated/progresses to gastric cancer, while high-grade
      dysplasia with gastric markers or gastric-enteropancreatic markers is included in
      the group with persistent or regressed cases. CONCLUSIONS: If confirmed in
      further studies, such results could modify the evaluation of epithelial gastric
      dysplasia, not only in terms of histochemical techniques, but also of
      immunohistochemical techniques.

PMID- 12063950
TI  - Analysis of microsatellite instability, K-ras gene mutation and p53 protein
      overexpression in intrahepatic cholangiocarcinoma.
AB  - BACKGROUND/AIMS: Genetic alterations are considered to play an important role in
      both the carcinogenesis and biological behavior of human malignancies. However,
      the clinical implications of intrahepatic cholangiocarcinoma are poorly
      understood. We investigated the microsatellite instability, K-ras gene mutations
      and p53 protein overexpression and their correlation with clinicopathological
      features to elucidate the clinical implications of genetic alterations in
      intrahepatic cholangiocarcinoma. METHODOLOGY: In twenty-three cases of surgically
      treated intrahepatic cholangiocarcinoma, microsatellite instability was examined
      by a PCR-SSCP analysis and K-ras gene mutation by a PCR-RFLP analysis, p53
      protein overexpression by immunohistochemistry. We evaluated the correlation
      between genetic alterations and clinicopathological features. RESULTS:
      Microsatellite instability was observed in one case (4.7%), K-ras gene mutation
      in 9 (39.1%) and positive staining for p53 protein in 5 (21.7%). The incidence of
      K-ras gene mutations in hilar type intrahepatic cholangiocarcinoma (6 of 8,
      75.0%) was significantly higher than that in peripheral type intrahepatic
      cholangiocarcinoma (3 of 15, 20.0%) (P < 0.05). Furthermore, the incidence of K
      ras gene mutations in patients with lymph node metastasis (58.3%) tended to be
      higher than that in patients without lymph node metastasis (18.2%). The patients
      with K-ras gene mutations showed a statistically significant worse survival rate
      than those without such mutations (P < 0.05). No statistically significant
      correlations were observed between the p53 overexpression and clinicopathological
      features. CONCLUSIONS: These data suggest that K-ras gene mutations may be
      involved in the carcinogenesis of intrahepatic cholangiocarcinoma, especially in
      hilar type intrahepatic cholangiocarcinoma, and thus may be correlated with
      aggressive biological behavior.

PMID- 12063951
TI  - Effect of short-term octreotide therapy and total parenteral nutrition on the
      development of biliary sludge and lithiasis.
AB  - BACKGROUND/AIMS: Both total parenteral nutrition and long-term octreotide
      treatment (> 2 months) may induce biliary sludge and lithiasis. However, the
      lithogenic capacity of the combination of the two treatments in the short-term is
      unknown. This study was undertaken to evaluate the lithogenic capacity of short
      term octreotide treatment (< 1 month) in patients with acute pancreatitis who are
      also receiving total parenteral nutrition, and to determine the evolution of
      patients who develop biliary sludge and/or lithiasis. METHODOLOGY: Thirty
      patients with acute pancreatitis were studied (21 males, 9 females; average age:
      38). All patients received total parenteral nutrition and analgesics. In a double
      blind random manner, 15 patients were treated with a continuous subcutaneous
      administration of octreotide (200 micrograms/8 h) and a further 15 patients
      received placebo. Biliary sludge and/or lithiasis were examined by
      ultrasonography. An echographic examination of the gallbladder was performed
      every seven days while the patients were in hospital. They were followed up every
      month, when another ultrasound of the gallbladder was carried out. RESULTS:
      Sixteen patients (53%) developed sludge: ten (67%) from the octreotide group and
      six (33%) from the placebo group (P = 0.29). Two of the patients from the
      octreotide group had microlithiasis (P = 0.34) and a cholecystectomy was
      required. In the other 14 patients, sludge had disappeared by the time of the
      check-up performed one month after discharge. CONCLUSIONS: Short-term octreotide
      treatment does not increase the risk of developing biliary sludge and/or
      lithiasis in patients also receiving total parenteral nutrition. Biliary sludge
      formed during total parenteral nutrition and short-term octreotide therapy may
      disappear when patients begin oral intake. Therefore, preventive measures are not
      required.

PMID- 12063952
TI  - Evaluation of gallbladder function in patients with non-diabetic chronic renal
      failure by quantitative radionuclide cholescintigraphy.
AB  - BACKGROUND/AIMS: We investigated quantitatively the motor function of the
      gallbladder in patients with non-diabetic chronic renal failure by the Tc-99m
      DISIDA cholescintigraphy. METHODOLOGY: Twenty-four patients (13 males, 11
      females; aged 62.0 +/- 16.2 years) with non-diabetic chronic renal failure were
      included in this study. All cases had normal gallbladder diagnosed by
      ultrasonography and normal liver function without symptoms or signs of
      cholecystitis. Fifteen normal controls (12 males, 3 females; aged 60.7 +/- 6.3
      years) were also included for comparison. Gallbladder function was represented as
      the filling fraction and the ejection fraction calculated using quantitative Tc
      99m DISIDA cholescintigraphy and was compared in the groups. RESULTS: The results
      showed no significant difference (P > 0.05) between non-diabetic chronic renal
      failure and controls in filling fraction (64.3 +/- 31.0 vs. 74.9 +/- 9.5) and in
      ejection fraction (54.4 +/- 26.5 vs. 49.9 +/- 4.2) by the independent Student's t
      test. CONCLUSIONS: Non-diabetic chronic renal failure seems not to impair
      gallbladder function although non-diabetic chronic renal failure patients had a
      tendency toward a decreased filling fraction. The high variability of filling
      fraction and ejection fraction observed in our patients implies that the
      determinants of gallbladder functions in non-diabetic chronic renal failure
      patients may be multiple in nature.

PMID- 12063953
TI  - The assessment of biliary CA 125, CA 19-9 and CEA in diagnosing
      cholangiocarcinoma--the influence of sampling time and hepatolithiasis.
AB  - BACKGROUND/AIMS: This study was conducted to assess the clinical value of biliary
      CA 19-9, CA 125 and CEA sampled in different situations for the diagnosis of
      cholangiocarcinoma. METHODOLOGY: Bile was obtained from patients with bile duct
      obstruction on the day of biliary drainage and 3 days later separately. The
      etiology of biliary obstruction included choledocholithiasis (N = 51),
      hepatolithiasis (N = 19) and cholangiocarcinoma (N = 28). Patients of the former
      two conditions were all complicated with cholangitis. RESULTS: The sensitivity of
      biliary CEA, CA 19-9 and CA 125, whenever checked were all less than 70%. The
      biliary CEA and CA 19-9 were elevated in the presence of cholangitis. In
      addition, the biliary CEA was also increased in the patients with
      hepatolithiasis. The specificity of CA 125 was better than those of CEA and CA 19
      9 (75.7% vs. 33.3% and 60%, respectively) on the day of biliary drainage. The
      diagnostic efficiency was slightly improved when combining biliary CA 125 and
      CEA. CONCLUSIONS: As the biliary CA 125 was less affected by inflammation and
      hepatolithiasis, it is more useful than CEA and CA 19-9 in the diagnosis of
      cholangiocarcinoma. The single tumor marker test of CA 125 or combined tumor
      marker test of CEA and CA 125 may be used as a useful complement to other
      investigative methods to differentiate benign from malignant causes of the bile
      duct obstruction.

PMID- 12063954
TI  - Pre- and intraoperative evaluation of biliary system for successful laparoscopic
      cholecystectomy in porcelain gallbladder patients.
AB  - BACKGROUND/AIMS: A porcelain gallbladder is generally thought to be a relative
      contraindication for laparoscopic cholecystectomy because of the difficulties in
      grasping the calcified wall of the gallbladder with forceps and making a
      retraction which would create a good operation field. The aim of this study was
      to define the clinical criteria for safe laparoscopic cholecystectomy in the
      treatment of porcelain gallbladders. METHODOLOGY: Between January 1993 and
      December 2000, 4 patients with porcelain gallbladders underwent laparoscopic
      cholecystectomy in our department. The significant features of the biliary system
      which contributed to the surgical results were investigated in these patients.
      RESULTS: All 4 patients were successfully treated by means of laparoscopic
      cholecystectomy. The confluence of the cystic duct was clearly demonstrated on
      the preoperative cholangiogram in all patients. Furthermore, the neck portion of
      the gallbladder wall, revealed no calcification on the CT scans of 3 patients,
      although the whole wall of the gallbladder, including the neck portion, showed a
      circumferential calcification in the remaining patient. Laparoscopic exposure and
      dissection of the Calot's triangle was relatively easy to perform in the former
      and was difficult in the latter, and thus, an anterograde laparoscopic
      cholecystectomy was the procedure of choice. Intraoperative cholangiography
      clearly demonstrated the confluence of the cystic duct in all of the patients.
      CONCLUSIONS: Porcelain gallbladder is an indication for laparoscopic
      cholecystectomy, especially in cases of a patent cystic duct and an uncalcified
      wall in the neck portion of the gallbladder. Laparoscopic cholecystectomy might
      be an indication for selected patients with porcelain gallbladder when an
      uncalcified and patent cystic duct are evident in pre- and intraoperative
      cholangiograms.

PMID- 12063955
TI  - Study of the intrahepatic surgical margin of hilar bile duct carcinoma.
AB  - BACKGROUND/AIMS: The diagnosis and treatment for hilar bile duct carcinoma has
      greatly improved. Frozen section is one of the modalities used to determine the
      intrahepatic surgical margin and the surgical approach for tumor resection. But
      we are sometimes faced with the case where we are perplexed whether to carry out
      additional surgical resection or not according to the result of frozen section,
      due to its inaccuracy. We studied herein the relation between the prognosis and
      the intrahepatic surgical margin according to the result of frozen section.
      METHODOLOGY: We reviewed 23 cases of hilar bile duct carcinoma whose intrahepatic
      surgical margin was determined by frozen section and studied the cause of death
      and surgical procedure. Results of the frozen sections were compared with the
      permanent paraffin sections. RESULTS: The overall survival rates at 1, 3 and 5
      years after operation were 68.1, 41.3, and 33.0%, respectively. The accuracy,
      sensitivity and specificity of frozen section was 56.5%, 75.0%, and 46.7%,
      respectively. CONCLUSIONS: We concluded that by evaluating the diagnosis of
      frozen section during the surgery it was difficult to determine intrahepatic
      surgical margin. Aggressive hepatic resection sometimes causes a high risk of
      hepatic failure in which case the histological diagnosis of the frozen section
      throughout should not be carried out.

PMID- 12063957
TI  - Association of Helicobacter pylori infection with ischemic stroke of non-cardiac
      origin: the BAT.MA.N. project study.
AB  - BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has been associated
      with several vascular obstructive disorders. The infection induces the production
      of proinflammatory cytokines that could increase platelet aggregates in
      circulation. The aim of this case-controlled study was to evaluate the prevalence
      of H. pylori infection in patients with acute ischemic stroke not related to
      cardiac causes. METHODOLOGY: A group of 80 consecutive patients (58 males, age
      range: 49-65 years) with acute ischemic stroke was studied. All patients received
      a cranial CT and/or brain magnetic resonance imaging scan, extracranial vessel
      duplex ultrasonography, and transthoracic echocardiography. H. pylori infection
      was diagnosed by means of both 13C urea breath test and IgG antibodies to H.
      pylori. A group of 320 blood donors (232 males and 88 females, age range: 49-65
      years) matched for sex and age served as controls. Among the patients, we
      investigated the presence of hypertension, cholesterol and glucose levels in
      serum, fibrinogen in plasma and the smoking habit. RESULTS: The presence of H.
      pylori infection was higher in patients than in controls: 64/80 (80%) versus
      190/320 (59.4%) (P < 0.001); when analyzed for sex in 45/58 (77.5%) among male
      patients and in 139/232 (59.9%) among controls (P < 0.05); of the females 19 out
      of 22 (86.3%) patients were infected at variance with only 51/88 (57.9%) of the
      controls (P < 0.05). Classical risk factors for stroke did not differ among
      patients with and without H. pylori infection. H. pylori infection was not
      differently associated with current smoking, serum total cholesterol and glucose
      levels, fibrinogen value in plasma and hypertension when compared to the H.
      pylori-negative status. CONCLUSIONS: H. pylori infection appears to be
      significantly more frequent in middle-aged patients with acute ischemic stroke
      than in controls.

PMID- 12063956
TI  - Intestinal type cholangiocarcinoma of intrahepatic large bile duct associated
      with hepatolithiasis--a new histologic subtype for further investigation.
AB  - Intestinal metaplasia is regarded as a possible predisposing factor of cancer,
      particularly of the intestinal type adenocarcinoma. The clinicopathologic
      features of intestinal type adenocarcinoma have been well documented in the
      stomach, and intestinal metaplasia and intestinal type adenocarcinoma has also
      been reported in the gallbladder. However, regarding the intrahepatic bile ducts,
      the clinicopathologic features are not yet clear and there have been no reports
      in English literature on intestinal type intrahepatic cholangiocarcinoma. We
      report a case of intestinal type cholangiocarcinoma associated with
      hepatolithiasis in the large intrahepatic bile duct. The tumor showed mainly
      intraductal papillary growth primarily composed of absorptive columnar cells.
      Particularly, Paneth cell metaplasia of carcinoma cells was widespread, and
      goblet cells and neuroendocrine cells were also observed in the carcinoma tissue,
      to a varied degree. It showed an intraluminal spread along the dilated
      intrahepatic ducts with minimal ductal stromal invasion. In the vicinity of the
      tumor, intestinal metaplasia was also identified in the adjacent hyperplastic and
      dysplastic bile duct epithelium. Some bile ducts contained stones and the mural
      glands of the bile ducts showed hyperplastic change secondary to stones. This
      case is considered to provide the evidence supporting the concept of the
      metaplasia-dysplasia-carcinoma sequence via intestinal metaplasia in the stone
      containing intrahepatic bile ducts.

PMID- 12063958
TI  - Pancreatic resection with ultrasonically activated scalpel: preliminary
      observations.
AB  - BACKGROUND/AIMS: Resection of the pancreas was performed with a surgical knife,
      electrocautery, or an automatic stapler. We histologically and radiologically
      evaluated the applicability of the ultrasonically activated scalpel (Coagulating
      Shears, CS, Ethicon Endo-Surgery, Cincinnati, OH, USA) for resecting pancreatic
      parenchyma and reported our clinical observations on the use of the coagulating
      shears. METHODOLOGY: Resection of the pancreas was performed with the coagulating
      shears in 8 patients and with electrocautery in 5. The pancreas was transected
      with blunt mode of the coagulating shears at output power level of 3. Histologic
      thermal degeneration of the surface was evaluated with hematoxylin-eosin and Azan
      Mallory staining. Radiologic pancreaticography was carried out on 4 resected
      specimens. We report 8 practical applications of the coagulating shears and
      compared its use with that of electrocautery in pancreatic surgery. RESULTS:
      Histologically, a coagulum of degenerated tissue completely closed each end of
      the vessels in the transected surface of all cases. The mean breadth of thermal
      degeneration resulting from the use of the coagulating shears was significantly
      less than that caused by electrocautery (1.33 +/- 0.21 vs. 3.05 +/- 0.34 mm,
      respectively) Pancreaticograms showed the closed branches of the pancreatic duct,
      but the closed main pancreatic duct had burst in 1 of 4 cases. Clinically,
      pancreatic fistula occurred in 1 of 8 patients who underwent pancreatic surgery
      with the coagulating shears. CONCLUSIONS: Pancreatic resection with the
      coagulating shears might be effective and feasible as long as the main pancreatic
      duct is ligated.

PMID- 12063959
TI  - Accumulation of mast cells and macrophages in focal active gastritis of patients
      with Crohn's disease.
AB  - BACKGROUND/AIMS: Recent studies have shown that focal active gastritis seems to
      be the typical gastric pathology in Crohn's disease. The aim of this study was to
      compare the incidence of focal active gastritis, Helicobacter pylori infection
      and distribution of gastric mast cells and macrophages in patients with Crohn's
      disease, ulcerative colitis and H. pylori gastritis without inflammatory bowel
      disease. METHODOLOGY: Patients with histologically confirmed Crohn's disease (n =
      25) or ulcerative colitis (n = 25) and control patients without inflammatory
      bowel disease (n = 25) were included in this study. Biopsy specimens were
      obtained from the antrum and corpus of each patient, and stained with hematoxylin
      and eosin and immunostained using antibodies to tryptase (AA1) and CD68. The
      number of mast cells and macrophages located in the lamina propria was
      determined. RESULTS: Focal active gastritis was detected in 54% of H. pylori
      negative patients with Crohn's disease, but it was not found in patients with
      ulcerative colitis nor in the control group. The density of mast cells and
      macrophages in the lamina propria of H. pylori-positive patients was
      significantly higher than in H. pylori-negative patients in all groups. In the
      Crohn's disease group, the number of mast cells (antrum; 83 +/- 11, body; 89 +/-
      11/mm2) and macrophages (antrum; 94 +/- 22, body; 92 +/- 17/mm2) in the lamina
      propria of H. pylori-negative patients with focal active gastritis was halfway
      between that in H. pylori-positive and H. pylori-negative patients. In focal
      active gastritis, mast cells accumulated at the border of focal active gastritis,
      whereas macrophages accumulated in the center of such lesions. CONCLUSIONS: Our
      findings indicated that the diagnosis of focal active gastritis, using
      immunostain for mast cells and macrophages, is the histological hallmark of
      gastric Crohn's disease. Macrophages might be associated with the formation of
      focal active gastritis in patients with Crohn's disease.

PMID- 12063960
TI  - Combined cytologic and histologic diagnosis of liver tumors via one-shot
      aspiration.
AB  - BACKGROUND/AIMS: Ultrasound-guided fine needle aspiration is considered to be a
      safe alternative in diagnosing liver tumors. Combined cytologic and histologic
      preparation via one-shot fine needle aspiration was evaluated, especially in
      outpatients. METHODOLOGY: During a 1-year period, 95 patients (including 57
      outpatients and 38 inpatients) who had received 97 sessions of fine needle
      aspiration and had final diagnosis were enrolled. Using a 22-gauge needle, the
      aspirate from liver tumor was processed for cytology and cell block histology
      simultaneously in patients without ascites and/or bleeding tendency. RESULTS:
      From 94 malignant and 3 benign tumors, the accuracy of cytology was 88.7%; while,
      the difference between outpatients and inpatients was not significant (91.2% vs.
      85%). No complication after fine needle aspiration was elicited in both groups.
      The rates of inadequate specimen preparation for cytology and histology were 0%
      and 13.4%, the false-negative rates of malignancy were 11.7% for cytology and 16%
      for histology. The inadequate and false-negative rates of histology were not
      associated with gender, underlying liver cirrhosis, or tumor size, type, and
      location. CONCLUSIONS: Ultrasound-guided 22-gauge one-shot fine needle aspiration
      is safe, convenient and reliable in diagnosing liver tumor, and can be performed
      in outpatients meticulously.

PMID- 12063961
TI  - Helicobacter pylori accelerates the biliary epithelial cell proliferation
      activity in hepatolithiasis.
AB  - BACKGROUND/AIMS: Several authors have reported the presence of H. pylori in the
      human biliary tract. The aim of this study was to investigate the influence of
      the presence of H. pylori on the epithelial cell proliferation activity in the
      biliary tract with hepatolithiasis. METHODOLOGY: A histopathological examination
      and polymerase chain reaction were used to detect the presence of H. pylori from
      fourteen patients with hepatolithiasis. The cell proliferation activity in the
      biliary epithelia was determined using proliferating cell nuclear antigen
      staining. RESULTS: A histopathological examination and polymerase chain reaction
      analysis demonstrated H. pylori to be detected in 5 (37%) and 4 (29%) out of 14
      patients, respectively. The proliferating cell nuclear antigen labeling index was
      significantly higher in the H. pylori-positive patients (28.3%) than in the H.
      pylori-negative individuals (4.9%). CONCLUSIONS: H. pylori is present in the
      biliary tract of patients with hepatolithiasis, while H. pylori promotes the
      formation of stones in the biliary tract. The development of intrahepatic
      cholangiocarcinoma might therefore be linked to the presence of H. pylori because
      of the accelerated activity of cell kinetics in the epithelium of the biliary
      tract.

PMID- 12063962
TI  - Hemodynamics in the microvasculature of thioacetamide-induced cirrhotic rat
      livers.
AB  - BACKGROUND/AIMS: To evaluate the hepatic microcirculatory changes in liver
      cirrhosis, in vivo microscopic findings were assessed quantitatively in cirrhotic
      rats. METHODOLOGY: Using in vivo microscopy, the blood flow velocity through
      terminal portal venules and terminal hepatic venules, and their diameters were
      measured. The rats were classified into a normal group, fibrosis group, and
      cirrhosis group, histopathologically. To estimate intrahepatic blood flow of the
      liver surface, laser-Doppler flowmeter was used for the three groups, and portal
      venous pressures were measured. RESULTS: Blood flow velocity through terminal
      portal venules increased significantly in cirrhosis rats. However, among the
      three groups, there were no significant differences with blood flow velocity
      through terminal portal venules, diameters of terminal portal venules and
      terminal hepatic venules. Portal venous pressure and intrahepatic blood flow of
      the liver surface increased significantly. CONCLUSIONS: These data indicate that
      pre-sinusoidal alterations to hemodynamics become manifest in the liver
      cirrhosis, which might be related to intrahepatic shunt formation.

PMID- 12063963
TI  - Resection of liver metastases from a virilizing steroid (lipoid) cell ovarian
      tumor.
AB  - The authors report the case of a 34-year-old woman who presented liver metastases
      from a virilizing lipoid cell ovarian tumor. The patient complained of right
      upper quadrant abdominal pain, strong virilization and secondary amenorrhea. She
      developed hirsutism and irregular menses at the age of 23, and a salpingo
      ooforectomy for a right ovarian lipoid cell tumor was performed. She was
      asymptomatic but 6 months before admission she presented abdominal pain. The
      computed tomography scan showed a large right-side hypodense liver lesion. Tumor
      and viral markers were normal. Serum testosterone was 7 ng/mL and the
      dehydroepiandrosterone was 2.5 ng/mL. A right trisegmentectomy was performed. Her
      recovery was uneventful, hormone levels returned to normal, and she has been
      asymptomatic after a follow-up of 6 months.

PMID- 12063964
TI  - Two subtypes in colorectal mucinous carcinoma in relation to microsatellite
      instability.
AB  - BACKGROUND/AIMS: Although some investigators have attempted to divide colorectal
      mucinous adenocarcinoma into two entities, there have been few reports describing
      microsatellite instability of each subtype. In this study, we elucidated the
      clinicopathological features of subtypes in mucinous carcinoma, especially the
      relationship between microsatellite instability and each subtype. METHODOLOGY:
      The present study included 33 patients with mucinous colorectal cancer. The 33
      patients were classified into two groups; the papillotubular type group (n = 22)
      and the mucocellular type group (n = 11). The clinicopathological aspects and
      microsatellite instability were examined. RESULTS: Significant differences were
      found between the papillotubular type group and the mucocellular type group
      regarding the following findings such as lymphatic invasion, lymph node
      metastasis, peritoneal metastasis, and Dukes stage. The mucocellular type group
      had 2 cases with high-frequency microsatellite instability, 7 cases with low
      frequency microsatellite instability and 2 cases with microsatellite stability.
      Conversely, the papillotubular type group included 12 cases with high-frequency
      microsatellite instability, 3 cases with low-frequency microsatellite instability
      and 7 cases with microsatellite stability. The ratio of cases with high-frequency
      microsatellite instability in the mucocellular type group (18.1%) was
      significantly lower than that of the papillotubular type group (54.5%) (P =
      0.0463). The 5-year survival rate of the mucocellular type group (29.1%) was
      significantly lower than that of the papillotubular type group (70.3%) (P =
      0.0282). CONCLUSIONS: Colorectal mucinous carcinoma needs to be classified into
      two groups, papillotubular type and mucocellular type, because of significant
      differences in microsatellite instability and patients' survival.

PMID- 12063965
TI  - Intraoperative colonic lavage with primary anastomosis vs. Hartmann's procedure
      for perforated diverticular disease of the colon: a consecutive study.
AB  - BACKGROUND/AIMS: The ideal treatment for complicated diverticulitis is still
      controversial. The Hartmann's procedure remains the favored option in patients
      with acute complicated sigmoid disease but there has been increasing interest in
      primary resection and anastomosis with intraoperative colonic lavage. A
      prospective study was carried out on 71 patients with peritonitis, comparing
      primary resection with intraoperative colonic lavage, and Hartmann's procedure.
      METHODOLOGY: Between January 1994 and September 1999, 71 patients underwent
      emergency laparotomy for diverticular peritonitis. Primary resection and
      anastomosis with intraoperative colonic lavage was performed in 29 patients
      (group I) and Hartmann's procedure in 42 patients (group II). All data were
      collected on standardized forms. RESULTS: There were no differences between the
      two groups according to clinical features, biology, severity of disease and
      operative delay. The mortality rate in group I and group II was, respectively, 7
      and 10% (P = 0.6). The incidence of postoperative complication was higher after
      Hartmann's procedure (P < 0.05). The mean hospital stay was significantly longer
      for the Hartmann's procedure compared to primary resection with intraoperative
      colonic lavage. CONCLUSIONS: Primary resection with intraoperative colonic lavage
      compares favorably with Hartmann's procedure for local or diffuse purulent
      peritonitis in complicated diverticulitis. It should be an alternative to the
      Hartmann's procedure in stercoral peritonitis.

PMID- 12063966
TI  - Subjects older than 60 years with negative findings on sigmoidoscopy should still
      undergo colonoscopy.
AB  - BACKGROUND/AIMS: The objective of this study was to evaluate the impact of age on
      the prevalence of proximal clinically important lesions in subjects without any
      rectosigmoid neoplasm. METHODOLOGY: The present study involved 497 patients (aged
      > or = 50 years old) who underwent a colonoscopy because of abdominal symptoms or
      positive fecal occult blood test. A proximal colon was defined as one proximal to
      a sigmoid colon. Clinically important lesions were defined as adenocarcinoma,
      tubular adenoma > or = 1 cm in diameter, or adenoma with villous histology or
      high-grade dysplasia. RESULTS: Of the 497 patients, 83 had clinically important
      lesions in the proximal colon. Of those 83, 53 patients had no neoplasm in the
      distal colon or rectum. In patients with no distal neoplasm, the prevalence of
      proximal clinically important lesions in subjects over 60 years old significantly
      exceeded that in patients aged 50-60 (39/105 vs. 14/125; P < 0.0001). In patients
      with distal neoplasm, the prevalence of proximal clinically important lesions in
      subjects over 60 was similar to that in 50 to 60-year-old subjects (16/119 vs.
      14/148; P = 0.406). CONCLUSIONS: Results suggest that subjects older than 60
      years old should still undergo a colonoscopy even if they have no neoplasm on
      sigmoidoscopy.

PMID- 12063967
TI  - RER and LOH association with sporadic colorectal cancer in Taiwanese patients.
AB  - BACKGROUND/AIMS: This association study was undertaken to determine replication
      error and loss of heterozygosity in colorectal tumors using a set of 10
      microsatellite markers linked to APC, hMSH2, hMLH1, DCC, P53, NM23, HPC1 and MET
      genes as well as tumor suppressor genes on 8p22. METHODOLOGY: Thirty-nine
      patients diagnosed and confirmed with sporadic colorectal cancer were biopsied.
      Their stored frozen tissues were subsequently retrieved for simultaneous analyses
      of replication error and loss of heterozygosity via an automated fluorescent
      microsatellite assay. RESULTS: Replication error was observed in 8/39 of the
      cases (20.5%) and had significantly higher frequency in the patients younger than
      60 yr (P = 0.049). More than one third of informative tumors showed loss of
      heterozygosity at P53, DCC and APC genes (57.9%, 35.3% and 33.3%, respectively).
      Loss of heterozygosity at TP53-Dint marker was significantly associated with
      survival status (P = 0.038) in which a higher frequency was observed in the
      patients who died from colorectal cancer. Of 22 informative tumors, 6 (27.3%)
      showed loss of heterozygosity at the D8S254 marker that is suspected to be near
      one or more tumor suppressor genes and was significantly associated with gender
      (P = 0.046). All 6 cases of loss of heterozygosity at D8S254 were found in male
      patients. The frequencies of loss of heterozygosity at the NM23, hMSH2, hMLH1 and
      HPC1 genes were 18.5%, 12.1%, 9.1% and 7.4%, respectively. None of the cases
      examined displayed loss of heterozygosity at the MET oncogene. CONCLUSIONS:
      Additional microsatellite markers other than those associated with colorectal
      cancer were used to conduct the study of genomic instability and alterations in
      colorectal cancer tumors. The present results for the sporadic occurrence of
      colorectal cancer in Taiwanese patients further extend the correlation of
      clinical pathology and prognosis with the analysis of replication error and loss
      of heterozygosity.

PMID- 12063969
TI  - Endoscopic ultrasonography in the preoperative staging of colorectal cancer.
AB  - BACKGROUND/AIMS: Endoscopic ultrasonography presents a significant progress in
      imaging methods for the examination of the digestive system and is commonly used
      in cancer staging. The aim of this study was to quantify the potential of this
      modality for diagnosis and staging of colorectal cancer. METHODOLOGY: Eighty
      patients with histologically proven colorectal cancer were included in this
      study. All patients were preoperatively diagnosed by colonoscopy and biopsies,
      abdominal computed tomography and endoscopic ultrasonography. The latter was also
      used to evaluate the depth of tumor invasion and presence of lymph node or
      distant metastasis prior to surgery. RESULTS: Endoscopic ultrasonography
      presented 100% sensitivity in cancer detection versus 60% for computed tomography
      (P < 0.001). Endoscopic Ultrasonography sensitivity in T, N, M and TNM staging
      was 93.8%, 93.8%, 92.5% and 82.5% with corresponding specificities of 99.2%,
      97.9%, 92.5% and 94.2%. Overall, Endoscopic Ultrasonography staging of the
      patients did not present statistically significant differences with histological
      staging (P > 0.05). CONCLUSIONS: Endoscopic ultrasonography is of satisfactory
      accuracy in diagnosis and preoperative staging of colorectal cancer.

PMID- 12063968
TI  - Different distribution of mast cells and macrophages in colonic mucosa of
      patients with collagenous colitis and inflammatory bowel disease.
AB  - BACKGROUND/AIMS: Chronic inflammatory cells in colonic mucosa is a
      histopathologic feature in patients with collagenous colitis and inflammatory
      bowel disease. The aim of this study was to compare the distribution of mast
      cells and macrophages in the colonic mucosa of patients with collagenous colitis,
      Crohn's disease, and ulcerative colitis. METHODOLOGY: Patients with
      histologically confirmed collagenous colitis (n = 13), Crohn's disease (n = 20)
      or ulcerative colitis (n = 20) and normal control patients (n = 20) were included
      in this study. Biopsy specimens were obtained from the sigmoid colon of each
      patient, and immunostained using antibodies to tryptase (AA1) and CD68. The
      number of mast cells and macrophages located in upper and lower part of the
      lamina propria was determined. RESULTS: The number of mast cells in the upper
      part of lamina propria in patients with collagenous colitis (286 +/- 89/mm2, mean
      +/- SD), Crohn's disease (330 +/- 84/mm2) and ulcerative colitis (355 +/-
      90/mm2), was higher than normal controls (201 +/- 44/mm2). The number of mast
      cells in the lower part of lamina propria in patients with Crohn's disease (345
      +/- 87/mm2) and ulcerative colitis (363 +/- 86/mm2) was higher than collagenous
      colitis (266 +/- 63/mm2) and normal controls (309 +/- 60/mm2). The number of
      macrophages in the lower part of lamina propria in patients with Crohn's disease
      (330 +/- 63/mm2) and ulcerative colitis (301 +/- 60/mm2) was higher than in
      collagenous colitis (247 +/- 46/mm2) and normal controls (242 +/- 52/mm2),
      although there were no significant differences in the number of macrophages
      present in the upper part of the lamina propria among the four groups.
      CONCLUSIONS: Our data showed the presence of a different distribution of mast
      cells and macrophages in collagenous colitis and inflammatory bowel disease, and
      these suggest that because mucosal mast cells have been implicated in the
      development of Th2 response collagenous colitis is more of a Th2 type reaction
      rather than Th1.

PMID- 12063970
TI  - The management of retrorectal congenital tumors.
AB  - Although retrorectal congenital tumors are still rare, the number of the observed
      ones is destined to increase, as methods by imaging become routinely used in the
      clinical practice. By presenting three clinical cases the authors describe the
      surgical technique of the anterior route they performed for the management of
      such formations. The abdominal approach had no postoperative complications, short
      hospital stay, no neurological consequences and good long-term results. There has
      been no evidence of recurrence thus far. Once diagnosed, the removal of
      retrorectal lesions should be mandatory. A precise definition of the extent of
      the tumors and of their relationships with the surrounding tissue and organs is
      necessary to perform maneuvers of total excision. For this reason an abdominal
      approach is recommended.

PMID- 12063972
TI  - All pathological T4 esophageal carcinomas should be categorized as stage IV.
AB  - BACKGROUND/AIMS: The prognosis of pathological T4 (pT4) esophageal carcinoma is
      still dismal, however, the current TNM classification categorizes some pT4
      cancers (pT4M0) as stage III. The purpose of this study was to evaluate of the
      relevance of this classification. METHODOLOGY: One hundred and thirty-five
      patients who underwent esophagectomy for pathological stage III (n = 85) and IV
      (n = 50) esophageal tumors were enrolled in the study. The outcomes and
      prognostic factors for these patients were examined. After the reclassification
      that pT4M0 tumors were categorized as stage IV, the two survival curves were
      compared between new stage III and IV. RESULTS: The 5-year survival rates for
      stage III and IV were 14.6%, 19.1%, respectively (P = 0.9). The 5-year survival
      rates for pT3N1M0 and pT4M0 were 21.1%, 0%, respectively (P < 0.0001). After the
      reclassification, the overall 5-year survival rates for new stage III and IV were
      24.0%, 14.2%, respectively (P = 0.004). Curative resection (P = 0.002),
      radiotherapy (P = 0.001), depth of tumor invasion (pT3; P = 0.0004, pT1; P =
      0.04) were the significant prognostic factors for stage III and IV carcinomas.
      Thirty-one (83.8%) of 37 patients with pT4 tumor had received non-curative
      esophagectomy. CONCLUSIONS: All pathological T4 esophageal carcinomas should be
      categorized as stage IV in the TNM classification.

PMID- 12063971
TI  - Metastasectomy and active specific immunotherapy for a large single melanoma
      metastasis.
AB  - A patient with a large duodenal melanoma metastasis, involving adjacent jejunum
      and colon, is presented. Treatment consisted of a combination of radical surgery
      and active specific immunotherapy by means of an autologous tumor cell vaccine
      and BCG after which a recurrence-free survival of now more than 10 years has been
      observed. The role of surgery and immunotherapy in the treatment of metastatic
      melanoma are discussed.

PMID- 12063973
TI  - Implantation of self-expanding metallic stent for patients with malignant
      stricture after failure of definitive chemoradiotherapy for T3 or T4 esophageal
      squamous cell carcinomas.
AB  - BACKGROUND/AIMS: Definitive chemoradiotherapy can have curative potential in
      unresectable patients with malignant stricture due to locally advanced esophageal
      carcinoma, however, dysphagia is the principal problem in patients who had
      recurrence or who did not respond to chemoradiotherapy. In this prospective
      study, we investigated the efficacy and feasibility of metallic stent
      implantation for patients with dysphagia after chemoradiotherapy failed.
      METHODOLOGY: Concurrent chemoradiotherapy was performed in 40 patients with
      severe dysphagia due to esophageal squamous cell carcinomas accompanied by T3 or
      T4 disease containing M1 lymph node (LYM) disease. A self-expanding metallic
      stent was inserted for patients with malignant stricture of the thoracic
      esophagus after failure of chemoradiotherapy using identical protocols. RESULTS:
      Of 40 patients, 13 (33%) achieved a complete response. However, 12 patients
      complained of severe dysphagia again after chemoradiotherapy despite a good
      performance status. Esophageal stricture of these 12 patients was caused by
      stable disease (n = 4), local progression (n = 5), and compression of metastatic
      lymph node (n = 3). Metallic stents were successfully inserted for all 12
      patients, and dysphagia improved in 10 (83%) of these 12 patients. Life
      threatening complication (17%) of sepsis in two patients was found in an early
      phase after stent insertion, although approximately 200 days had passed in a
      dysphagia-free state after chemoradiotherapy. CONCLUSIONS: Implantation of self
      expanding metallic stent for patients with malignant stricture after failure of
      chemoradiotherapy is effective, however, serious complication can occur in the
      early phase.

PMID- 12063974
TI  - Changes of plasma levels of gastrointestinal peptides over the course of acute
      pancreatitis. Any significance for the pathophysiology and treatment of acute
      pancreatitis?
AB  - BACKGROUND/AIMS: Acute pancreatitis may be accompanied by alterations of the
      secretion of pancreatic and gastrointestinal peptides as a result of pancreatic
      inflammation. These changes, that may constitute targets of therapeutic
      manipulation, led to the study of the serum levels of various pancreatic and
      gastrointestinal peptides over the course of acute pancreatitis before and after
      the administration of octreotide and ranitidine. METHODOLOGY: Concentrations of
      gastrin, glucagon, vasoactive intestinal peptide, neurotensin and pancreatic
      polypeptide were determined by radioimmunoassay in the plasma of 22 patients with
      acute pancreatitis on the first, sixth and 11th day of the disease. All patients
      were treated with octreotide s.c. while 14 of them were also administered
      ranitidine i.v. Treatment was initiated after taking the first blood sample.
      RESULTS: Mean gastrin levels in patients receiving ranitidine was 56.76 ng/L and
      in patients not receiving ranitidine 47.16 ng/L on the first day (pNS) remaining
      stable throughout the course of acute pancreatitis. Mean glucagon, vasoactive
      intestinal peptide, neurotensin and pancreatic polypeptide levels on the first
      day were 52.05 pmol/L, 8.90 pmol/L, 9.80 pmol/L and 22.06 pmol/L, respectively,
      and no changes were found through the course of acute pancreatitis. CONCLUSIONS:
      Plasma levels of gastrointestinal peptides remain constant over time and they are
      not significantly affected by the administration of octreotide or ranitidine.
      However more studies are necessary to document the significance of these
      findings.

PMID- 12063975
TI  - Inhibition of Helicobacter pylori infection by orally administered yolk-derived
      anti-Helicobacter pylori antibody.
AB  - BACKGROUND/AIMS: We studied highly specific chicken egg yolk-derived anti
      Helicobacter pylori antibody, and examined efficacy in inducing passive immunity
      and a bacteriostatic effect on H. pylori. METHODOLOGY: Heat-killed H. pylori were
      administered orally to hens, and specific anti-H. pylori antibody was purified
      from the yolk of eggs laid by these hens. The antibody's ability to inhibit H.
      pylori growth, urease activity, ammonia production, the cytopathic effects, and
      its effects on serum anti-H. pylori immunoglobulin G (IgG) production were
      investigated in vitro and in vivo. In addition, H. pylori-infected volunteers
      received the antibody orally and underwent repeated 13C-urea breath test after
      antibody ingestion. RESULTS: Anti-H. pylori antibody derived from egg yolk
      strongly inhibited growth of H. pylori and increased agglutination of H. pylori
      in vitro. It also strongly inhibited H. pylori-associated urease activity and
      ammonia production as well as the cytopathic effect of H. pylori on cultured
      cells. The antibody also inhibited serum anti-H. pylori IgG production and the
      incidence of acute gastritis in H. pylori-infected Mongolian gerbils. In
      volunteers, urea breath testing showed decreased urease activity after antibody
      ingestion. CONCLUSIONS: Anti-H. pylori antibody derived from egg yolk was
      specific for H. pylori. The antibody had a bacteriostatic effect on H. pylori,
      inhibited H. pylori urease activity, and inhibited H. pylori infection in
      Mongolian gerbils and humans.

PMID- 12063976
TI  - Tension-free inguinal hernia repair in "one-day surgery". Experience of 1091
      cases.
AB  - BACKGROUND/AIMS: In recent years new techniques to repair inguinal hernia have
      evolved in order to reduce recurrence rate and the overall costs of treatment of
      this pathology. This paper analyses our experience in verifying the theoretical
      advantages of the "tension-free" technique, after six years of this surgical
      practice. METHODOLOGY: We describe the experience of 1091 "tension-free" hernia
      repairs with open placement of a mesh in 1034 patients, under local anesthesia
      with a "one-day surgery" regimen; these patients were observed during the period
      1994 to 1999 at the Surgical Unit of Catholic University of Rome. The patients
      were between American Society of Anesthesia Status I to IV. Eight hundred
      patients underwent a mean follow-up of 29.7 months (range: 4-72) to evaluate the
      occurrence of late complications and recurrences. RESULTS: No mortality or major
      intraoperative complications was observed. The only minor intraoperative or
      postoperative complications encountered were easily managed. Early pain
      disappearance, fast convalescence and rapid resumption of working activity were
      observed. Six recurrences occurred in the patients undergoing follow-up (0.75%
      recurrence rate). CONCLUSIONS: Our data confirm the safety, rapidity, and
      reproducibility of the "tension-free" technique under local anesthesia performed
      with a "one-day surgery" regimen for inguinal hernia repair. These
      characteristics explain the diffusion of this surgical procedure with reduction
      of social costs.

PMID- 12063977
TI  - Pulmonary embolism following laparoscopic surgery: a report of two cases.
AB  - Laparoscopic abdominal surgery is considered a low-risk procedure for
      postoperative complications because of reduced surgical stress and earlier
      mobilization. We report two patients who experienced pulmonary embolism following
      laparoscopic surgery; one patient underwent umbilical hernia repair and the other
      cholecystectomy. Although pulmonary embolism is indeed rare after laparoscopic
      surgery, early detection and early treatment are determinative factors for a good
      prognosis. Therefore, medical caregivers must remember that pulmonary embolism
      can be a critical complication after laparoscopic surgery and preventive measures
      should be employed for high-risk subjects.

PMID- 12063978
TI  - Role of splenectomy in living-donor liver transplantation for adults.
AB  - BACKGROUND/AIMS: Splenectomy is occasionally required in liver transplantation.
      However, its indications and drawbacks have not been clearly defined in living
      donor liver transplantation. METHODOLOGY: Eleven of 59 adult living-donor liver
      transplantation recipients underwent splenectomy. Indications were
      thrombocytopenia in 6 cases, portal flow disturbances due to splenorenal shunt in
      four, and splenic infarction in one. The incidence of bacterial complications and
      changes in platelet counts and portal vein flow were evaluated. RESULTS: Two
      patients died of pneumonia and cerebral bleeding, respectively. Six events of
      bacterial infections occurred in the remaining nine patients. After splenectomy,
      a normal portal flow was achieved and the platelet count significantly increased.
      CONCLUSIONS: Splenectomy may be an acceptable option in patients with
      thrombocytopenia or when it is necessary to change the portal flow.

PMID- 12063979
TI  - Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels.
AB  - BACKGROUND/AIMS: Interferon-alfa is widely used for the treatment of chronic
      hepatitis C, and has been thought to have a preventive effect on the development
      of hepatocellular carcinoma. Hepatocellular carcinoma develops from chronic liver
      diseases such as chronic hepatitis C or liver cirrhosis. We studied the effect of
      interferon for liver cirrhosis with hepatocellular carcinoma after treating
      hepatocellular carcinoma itself. METHODOLOGY: To evaluate the preventive effect
      of this drug on local recurrence and/or new development of primary tumor after
      clearance of hepatitis C virus, 46 patients with hepatocellular carcinoma with
      low HCV-RNA level were randomized to receive recombinant interferon-alfa 2b (n =
      22) or not (n = 24) after being treated by transcatheter arterial
      chemoembolization and percutaneous ethanol injection therapy. In the interferon
      treated group, patients received 3 million international units of interferon-alfa
      2b intramuscularly three times a week for 4 months. In both groups, transcatheter
      arterial chemoembolization followed by percutaneous ethanol injection therapy was
      performed as an initial treatment and these therapies were repeated every 4-6
      months. Serum HCV-RNA levels of all 46 patients were under 0.5 Meq/mL by branched
      DNA probe assay. RESULTS: In the interferon-treated group, 11 of the 22 (50%)
      patients were HCV-RNA negative at the 6 months after completing the course of
      interferon therapy. HCV-RNA was undetectable during the observation period in 2
      of the 24 (9.5%) patients in the untreated group. The survival rate in the
      interferon-treated group was significantly higher than that in the untreated
      group (P = 0.01 by the log-rank test). Though there was no significant difference
      in the incidence of local recurrence in both groups, the incidence of secondary
      hepatocellular carcinoma was significantly lower in the interferon-treated group
      than that in the untreated group. Cox proportional hazards regression analysis
      validated interferon treatment as an independent predictor of hepatocellular
      carcinoma prognosis. CONCLUSIONS: We concluded that, if HCV-RNA level is low,
      interferon may be a therapy of choice in combination with transcatheter arterial
      chemoembolization and percutaneous ethanol injection therapy for the treatment of
      hepatocellular carcinoma.

PMID- 12063980
TI  - Chemosensitivity of primary hepatic neoplasms: a potential new approach to the
      treatment of hepatoma.
AB  - BACKGROUND/AIMS: Standard chemotherapy approaches for hepatic neoplasms are
      effective in only 20-30% of cases. The vast majority of patients treated with
      chemotherapy experience little or no benefit with considerable toxicity. In an
      effort to identify specific agents potentially effective in individual cases, 22
      individuals with a hepatoma were biopsied and their tumor cells were grown in
      culture such that the expanded tumor cell population could be assessed for
      chemosensitivity to 14 different commonly used chemotherapeutic agents.
      METHODOLOGY: Each agent was tested in 6 wells at 6 different doses scanning a
      range of concentrations known to occur in vivo corresponding to subpharmacologic
      levels to suprapharmacologic levels. The in vitro response of each tumor for each
      agent was determined on a 0- to 5-point scale where 0 equals not sensitive and 5
      equals extremely sensitive. Each of the tumors was successfully grown and
      expanded in culture over a 30- to 40-day period. Three individuals had their
      tumors biopsied and tested twice at 2 different time points. In addition, 2 liver
      specimens determined to be non-neoplastic liver specimens after removal were
      expanded in culture as controls to determine the sensitivity of normal non
      neoplastic cells to the same 14 chemotherapeutic agents. RESULTS: Assuming that
      tumors would be clinically sensitive to an agent if their in vitro sensitivity
      score is 3 or above, then only a minority of tumors could be identified as
      chemosensitive to the 14 agents tested. Moreover, of the 2 agents (doxorubicin
      and cisplatin) used most often clinically, only 14 of the 22 tumors were
      sensitive to either of these agents. Only 8 of the tumors demonstrated an in
      vitro sensitivity score of 5 for either of these 2 agents. Specifically, only 11
      of the 22 tumors were sensitive to doxorubicin and only 9 were sensitive to
      cisplatin. In contrast, 14 of the tumors showed in vitro sensitivity to 1 or more
      of the other 12 agents utilized for chemosensitivity determinations. CONCLUSIONS:
      These data demonstrate that hepatic tumors can be 1) grown in vitro and 2) tested
      for in vitro chemosensitivity. These data suggest that this methodology may
      identify tumors that are sensitive to specific chemotherapeutic agents and assist
      in the determination of which agents might be most useful in a given case.
      Selecting a chemotherapeutic agent for use using this methodology, should improve
      efficacy while toxicity would be minimized.

PMID- 12063981
TI  - Subsegmental transcatheter arterial embolization for small hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: The evaluation of long-term outcome of subsegmental
      transcatheter arterial embolization, which was designed to bring about sufficient
      anti-tumor effect, in the primary cases of small hepatocellular carcinoma.
      METHODOLOGY: We analyzed and compared the anti-tumor effect and the survival rate
      in the primary cases of solitary small hepatocellular carcinoma (< or = 3 cm)
      with cirrhosis treated by subsegmental transcatheter arterial embolization,
      chemolipiodolization or percutaneous ethanol injection therapy during the last
      eight years, retrospectively. RESULTS: The complete tumor necrosis by one session
      of subsegmental transcatheter arterial embolization, which means that treated
      tumor showed complete response and did not show local recurrence thereafter, was
      seen in approximately 50% of the cases. The rate of complete tumor necrosis was
      superior to that in the patients treated by chemolipiodolization although it was
      lower than that in the patients treated by percutaneous ethanol injection
      therapy. Both of the 5- and 7-year survival rates in the patients treated by
      subsegmental transcatheter arterial embolization were 41.2%. It was slightly
      higher than those in the other treatment groups without significant difference.
      CONCLUSIONS: Subsegmental transcatheter arterial embolization might be
      effectively performed as an initial treatment for the primary cases of the
      solitary small hepatocellular carcinoma when tumor was fully supplied by hepatic
      arterial blood regardless of small size.

PMID- 12063982
TI  - Accuracy of the preoperative determination of tumor markers in the
      differentiation of liver mass lesions in surgical patients.
AB  - BACKGROUND/AIMS: The diagnostic accuracy of tumor markers for differentiating
      focal liver lesions is not yet defined. Therefore, we carried out a retrospective
      analysis to address this issue. METHODOLOGY: We retrospectively evaluated 192
      consecutive patients with 289 focal liver lesions. The serum levels of AFP, PIVKA
      II, CEA, and CA19-9 were determined in 119 patients, while at least one of these
      values was lacking in the others. All patients underwent liver resection: 136
      patients had hepatocellular carcinoma, 39 metastases, 9 cholangiocarcinoma, 1
      mixed hepatocellular carcinoma-cholangiocarcinoma, and 7 benign lesions. RESULTS:
      At least one of the tumor markers examined was elevated in 169 of the 185
      patients with proven malignancy. In 92 cases, the elevation was marked. The mean
      levels of each tumor marker were significantly different among patients grouped
      according to the tumor type. ROC curves showed that 10 ng/mL was the optimal cut
      off level for AFP and hepatocellular carcinoma, and for CEA and colorectal liver
      metastases. CEA and CA 19-9 showed specific patterns of elevation in liver
      metastases and cholangiocarcinoma. CONCLUSIONS: Common tumor markers for focal
      liver lesions were significantly linked to the type of the tumor. These findings
      suggest that their selective estimation may be useful for the preoperative
      diagnosis of focal liver lesions.

PMID- 12063984
TI  - Percutaneous ethanol injection under CT fluoroscopy for hypervascular
      hepatocellular carcinoma following transcatheter arterial embolization.
AB  - BACKGROUND/AIMS: The present study was conducted to accurately monitor the
      pattern of ethanol distribution during percutaneous ethanol injection by computed
      tomography fluoroscopy and to examine the relationship between the distribution
      pattern and therapeutic effect. METHODOLOGY: Twenty-five hypervascular
      hepatocellular carcinomas were studied. Each was treated with transcatheter
      arterial embolization. However, as residual parts were detected, percutaneous
      ethanol injection under real-time computed tomography fluoroscopy was performed.
      For analysis, ethanol distribution and local recurrence rate were compared.
      RESULTS: Ethanol distribution in a tumor was classifiable into 3 patterns. In
      pattern 1, ethanol solution was distributed spherically. In pattern 2, ethanol
      solution spread forming linear boundaries indicating interruption of distribution
      by septa. In pattern 3, ethanol spread circumferentially only along the periphery
      sparing the central part of a tumor. The 6-month recurrence rate of the tumors in
      which ethanol solution was distributed to the whole viable part was 25% (pattern
      1), 100% (pattern 2) and 0% (pattern 3), respectively. CONCLUSIONS: In the tumors
      showing distribution pattern 3 by computed tomography fluoroscopy, a combination
      therapy of transcatheter arterial embolization and percutaneous ethanol injection
      was more effective than in other patterns. Computed tomography fluoroscopy was
      useful for accurate monitoring and predicting the therapeutic effect of
      percutaneous ethanol injection.

PMID- 12063983
TI  - Expression of the Ets-1 proto-oncogene is linked to cell differentiation of human
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Ets-1 regulates the expression of a number of genes related to
      remodeling of the extracellular matrix. Ets-1 is associated with the occurrence
      of invasive processes, proliferation and differentiation. Less is known about the
      biological functions of Ets-1 in human hepatocellular carcinoma. In an attempt at
      elucidation, we examined immunohistochemically hepatocellular carcinoma followed
      by application of genetic techniques. METHODOLOGY: We performed
      immunohistochemical analysis on tissue from 59 Japanese patients undergoing
      surgical resection of hepatocellular carcinoma using the antibody against human
      Ets-1. We compared Ets-1 expression in relation to clinicopathological findings.
      In situ hybridization and reverse transcription-polymerase chain reaction were
      also performed to confirm the expression of Ets-1 messenger RNA in hepatocellular
      carcinoma tissues. RESULTS: In specimens from 59 patients with hepatocellular
      carcinoma, 41 (70%) showed positive staining for Ets-1 protein. The expression of
      Ets-1 messenger RNA was also observed in hepatocellular carcinoma tissues by in
      situ hybridization and reverse transcription-polymerase chain reaction. The
      expression of Ets-1 correlated with histological differentiation of
      hepatocellular carcinoma (P < 0.05). Ets-1 was positive in 2 (50%) of the 4 well
      differentiated hepatocellular carcinomas and in 28 (64%) of the 44 moderately
      differentiated hepatocellular carcinomas, whereas all the 11 poorly
      differentiated hepatocellular carcinomas were positive for Ets-1 staining. Ets-1
      protein was expressed more strongly at the peripheral than the central area of
      the tumor. Otherwise, no particular correlation was evident in terms of
      clinicopathological factors. CONCLUSIONS: We found Ets-1 to be expressed in human
      hepatocellular carcinoma, particularly at the peripheral area of the tumor. As
      this expression is linked to cell differentiation, this gene may yield biological
      information relative to this malignant tumor of the liver.

PMID- 12063985
TI  - Interferon-alpha-2b and ribavirin for retreatment of chronic hepatitis C.
AB  - BACKGROUND/AIMS: Subjects with chronic hepatitis C who fail treatment with
      interferon-alpha are generally divided into two groups: "relapsers" who
      normalized serum aminotransferase activity and have undetectable viral RNA during
      treatment and "non-responders" who do not achieve these results. The aim of this
      study was to examine retreatment of such subjects. METHODOLOGY: We studied 117
      subjects with chronic hepatitis C who failed treatment with interferon-alpha, 87
      of whom were "non-responders" and 30 "relapsers." Retreatment was with either
      interferon-alpha-2b plus ribavirin for 48 weeks or with interferon-alpha-2b plus
      placebo for 24 weeks followed by 24 weeks of combined therapy. RESULTS: Sustained
      response rates, defined as undetectable viral RNA in serum 6 months after
      retreatment, were 53% in "relapsers" and 10% in "non-responders" (P < 0.005).
      There was no significant difference if ribavirin was given for 24 or 48 weeks. In
      "non-responders" infected with genotypes other than type 1, 42% achieved a
      sustained response compared to 5% infected with genotype 1 (P = 0.027; odds ratio
      7.09). CONCLUSIONS: Treatment with interferon-alpha-2b plus ribavirin is
      effective in approximately 50% of "relapsers" and "non-responders" infected with
      non-type 1 genotypes of hepatitis C virus. This therapy is only marginally
      effective in "non-responders" infected with genotype 1a or 1b.

PMID- 12063986
TI  - Intermittent total pedicular clamping in hepatic resections in non-cirrhotic
      patients.
AB  - BACKGROUND/AIMS: Evaluation of intermittent total pedicular clamping in hepatic
      resections in non-cirrhotic patients. METHODOLOGY: A prospective study was made
      of 72 patients submitted to hepatic resections using intermittent total pedicular
      clamping. Patients were placed in 5 groups for analysis according to the duration
      of liver ischemia (each 20 minutes). Tolerance of liver ischemia was assessed by
      analysis of postoperative morbimortality and biochemical test. RESULTS: Five
      patients (6.9%) died during the postoperative period and sixteen patients (23.8%)
      developed specific complications, however, none of the variables analyzed in this
      study proved to be an independent risk factor for the development of
      postoperative morbimortality. The transaminases presented a statistically
      significant relationship with duration of ischemia (P < 0.002), while the late
      rise was influenced by postoperative mortality (P < 0.009). Prothrombin time was
      influenced by the duration of ischemia and by postoperative mortality (P = 0.014)
      but, on the other hand, the bilirubin levels only showed the influence of
      mortality (P < 0.002). CONCLUSIONS: Immediate postoperative liver function was
      better preserved in patients submitted to less than 80 minutes of clamping. The
      late rise of bilirubin and transaminases and the drop in prothrombin time could
      be considered indicators of a bad postoperative course.

PMID- 12063987
TI  - Hepatic primary and secondary malignancies: comparison of helical CT and helical
      CT during arterial portography.
AB  - BACKGROUND/AIMS: To compare the sensitivity of helical CT to that of helical CT
      arterial portography in the detection of hepatic primary or secondary
      malignancies, in 20 patients who subsequently underwent surgery to confirm
      findings. METHODOLOGY: Twenty patients with suspected primary hepatic or
      secondary malignancies who all underwent helical CT and helical CT arterial
      portography preoperatively were prospectively evaluated. All the images were
      reviewed by two radiologists. The results were subsequently correlated with
      surgical and pathological findings. The sensitivity and the positive predictive
      values for lesion detection were determined for each modality. RESULTS: There
      were 39 pathologically confirmed hepatic malignant lesions. The overall
      sensitivity and positive predictive value of helical CT arterial portography were
      87.1% and 82.5%, respectively, while of helical CT were 84.6% and 94.2%,
      respectively. CONCLUSIONS: Helical CT arterial portography and helical CT of the
      liver were approximately equivalent for lesion detection in patients who were
      evaluated preoperatively for resection of liver malignancies. The lower cost and
      non-invasive nature of helical CT suggest that it should be the preferred
      modality.

PMID- 12063988
TI  - Significance of the molar ratio of branched-chain amino acids to tyrosine before
      hepatectomy.
AB  - BACKGROUND/AIMS: To predict the degree of liver fibrosis and select a safe
      operative procedure, the correlation between liver fibrotic ratio and
      preoperative liver function variables were analyzed, and the significance of the
      molar ratio of branched-chain amino acids to tyrosine determined preoperatively
      was investigated. METHODOLOGY: Forty-four patients with hepatectomy were enrolled
      in this study. Liver tissue specimens excised from the patients were stained by
      Azan-Mallory's method. The liver fibrotic ratio was measured using an Image
      Cytometer. The correlation between liver fibrotic ratio and preoperative liver
      function values, including the serum level of branched-chain amino acids to
      tyrosine, were determined. RESULTS: The degrees of liver fibrosis (normal group,
      1.4 +/- 0.7%; chronic hepatitis group, 4.5 +/- 2.8%; cirrhosis group, 8.4 +/-
      2.4%) correlated significantly with preoperative liver function values such as
      branched-chain amino acids to tyrosine, hepaplastin test, type IV collagen 7s
      domain, total bilirubin, indocyanine green clearance retention rate at fifteen
      minutes, and platelet count. The serum level of branched-chain amino acids to
      tyrosine showed the most-significant correlation with the degree of liver
      fibrosis. CONCLUSIONS: The serum level of branched-chain amino acids to tyrosine
      correlates well with the degree of liver fibrosis, and this value is a useful
      preoperative parameter for predicting the degree of liver fibrosis and for
      selecting a safe operative procedure.

PMID- 12063989
TI  - Monitoring of liver metabolic function during interferon-alpha therapy and its
      relationship to treatment outcome in chronic hepatitis C patients.
AB  - BACKGROUND/AIMS: Interferon is considered the cornerstone in the therapy of
      chronic hepatitis C patients. Experimental studies have shown that interferon
      administration may influence liver metabolic activity. However, data concerning
      the monitoring of liver metabolic function during a therapeutic course of
      interferon in chronic hepatitis C patients are scanty. The MEGX
      (monoethylglycinexylidide) test has been used in diagnostic and prognostic
      assessment of chronic liver disease as a quantitative liver function test. In
      this study our aim was to non-invasively monitor liver function in chronic
      hepatitis C patients during a course of interferon-alpha therapy and to evaluate
      whether the presence of modifications in liver metabolic function might influence
      the therapeutic outcome. METHODOLOGY: We studied 22 patients with biopsy-proven
      chronic hepatitis C before, during (1st, 3rd and 6th month of therapy), and three
      months after interferon-alpha (3 million units thrice weekly for six months)
      using MEGX test to monitor liver function. RESULTS: During the longitudinal study
      no significant differences were observed between pretreatment MEGX30 values and
      those obtained during interferon treatment or at the end of follow-up, both
      considering patients together or grouped according to treatment outcome
      (Responders vs. Non-responders). Analysis of the MEGX30 variations during therapy
      showed that they were evenly distributed between responder and non-responder
      patients. Furthermore, during interferon therapy none of the patients reached a
      MEGX30 value compatible with severely impaired liver function. CONCLUSIONS: Our
      results suggest that although a discrete prevalence of modifications in liver
      metabolic function occurs in chronic hepatitis C patients during interferon
      therapy they do not seem to have clinical relevance or influence therapeutic
      outcome.

PMID- 12063990
TI  - Effects of losartan, somatostatin and losartan plus somatostatin on portal
      hemodynamics and renal functions in cirrhosis.
AB  - BACKGROUND/AIMS: Several drugs have been used to reduce portal hypertension.
      Losartan constitutes arteriolar and venous vasodilation by inhibiting the effects
      of the increased angiotensin II in cirrhotic patients. In this study, we analyzed
      the effects of losartan, when used alone and when combined with somatostatin, on
      portal and renal hemodynamics. METHODOLOGY: Seventeen patients with cirrhosis
      were enrolled. During the study, the patients were administered 250 micrograms of
      somatostatin i.v. bolus and subsequent infusion at a rate of 250 micrograms/hr
      for 2 hours on the second day; 25 mg losartan orally on the fourth day; and
      losartan and somatostatin together, in the same doses as the second and the
      fourth day, were given on the sixth day. RESULTS: The portal flow volume and the
      velocity that were measured after the administration of somatostatin, losartan
      and the combination of each drug, were found to be increased when compared with
      the initial values (P < 0.001). Additionally, the creatinine clearances were
      increased and statistically significant with somatostatin. CONCLUSIONS:
      Considering its low cost, easy usability, long lasting effect, we suggest that
      losartan can be used as an alternative treatment in the clinical conditions where
      portal pressure should be reduced and can be combined with somatostatin without
      any significant adverse effects.

PMID- 12063991
TI  - Impaired response to high-dose interferon treatment in African-Americans with
      chronic hepatitis C.
AB  - BACKGROUND/AIMS: The prevalence of hepatitis C virus infection in the USA is
      higher among African-Americans than among Caucasians. Despite this, little
      information is available on the course of hepatitis C virus infection in Blacks
      and in other minority groups. The aim of this retrospective case-control study
      was to determine the response rate to high dose interferon-alpha treatment in two
      racial groups with chronic hepatitis C virus infection. METHODOLOGY: Thirty-one
      African-Americans and 62 Caucasians with chronic hepatitis C were considered in
      the study. The subjects were matched for gender, age, presence/absence of
      cirrhosis, histologic score, and viral genotype. All were treated with interferon
      alpha (5 mU/day for 12 months). Three end-points (on-therapy, after 6 months of
      interferon-alpha, end-of-therapy, at the end of the 12 months of treatment, and
      off-therapy, 6 months after treatment) were chosen to describe the response to
      interferon-alpha treatment. RESULTS: African-Americans had a significantly
      reduced response to interferon-alpha as compared to Caucasians at all end-points.
      At the on-therapy end-point, 26% of African-Americans were HCV-RNA negative and
      had normal transaminases level as compared to 60% of the Caucasians (P < 0.01);
      at the end-of-therapy end-point the rates were, respectively, 10% and 53% (P <
      0.0001). No differences were detected in terms of pretreatment serum ALT, HCV
      RNA, iron and ferritin levels or hepatic iron contents between the two groups.
      CONCLUSIONS: African-Americans have a reduced response to high-dose interferon
      alpha treatment as compared to Caucasians. Both environmental and genetic factors
      may be implicated in this impaired ability to clear hepatitis C virus infection.

PMID- 12063992
TI  - Simultaneous Doppler measurement of portal venous peak velocity, hepatic arterial
      peak velocity, and splenic arterial pulsatility index for assessment of hepatic
      circulation.
AB  - BACKGROUND/AIMS: Quantitative Doppler assessment of hepatic circulation is widely
      performed in patients with cirrhosis. Since few studies have attempted to
      evaluate the various parameters simultaneously, we sought to examine the
      applicability and possible advantages of such simultaneous measurement for
      assessment of hepatic function. METHODOLOGY: In 64 patients (21 with cirrhosis,
      17 with chronic hepatitis, and 26 with no liver disorder) we prospectively
      performed Doppler measurement of right portal venous peak velocity (PVPV), right
      hepatic arterial peak systolic velocity (HAPSV) and splenic arterial pulsatility
      index (SAPI) and calculated a novel parameter, the hepatic circulatory index
      (HCI). The HCI was calculated using the formula: HCI (cm2/s2) = PVPV (cm/s) x
      HAPSV (cm/s)/SAPI. RESULTS: Not every Doppler parameter was useful in itself for
      quantitative assessment of liver function. On the other hand, hepatic circulatory
      index was significantly higher in controls (1275.1 +/- 297.5) than in patients
      with hepatitis (931.7 +/- 270.5, P = 0.0003), or cirrhosis (586.4 +/- 264.9, P <
      0.0001) and was highly correlated with the plasma clearance rate of indocyanine
      green (KICG; r = 0.848, P < 0.0001). CONCLUSIONS: Hepatic circulatory index was
      correlated with KICG, which reflects hepatic circulation. The hepatic circulatory
      index is a novel parameter of hepatic circulation that can be measured easily at
      bedside, accurately reflecting hepatic circulatory status.

PMID- 12063993
TI  - Combination thymosin-alpha 1 and interferon-alpha 2b in the treatment of anti-HBe
      positive chronic hepatitis B in Turkey.
AB  - BACKGROUND/AIMS: The most prevalent type of chronic hepatitis B in Turkey is anti
      HBe-positive. No consistently effective therapy is yet available for the
      treatment of these patients. The aim of this study was to assess the efficacy and
      safety of interferon-alpha and thymosin-alpha 1 combination in the treatment of
      naive anti-HBe-positive and HBV DNA-positive chronic hepatitis B patients.
      METHODOLOGY: Twenty-one patients were enrolled in the study. All patients had
      documented anti-HBe-positive, HBV DNA-positive chronic active hepatitis B without
      evidence of cirrhosis. Patients received a 26-week combination course of 1.6 mg
      thymosin-alpha 1 subcutaneously twice a week and 10 MIU interferon-alpha
      subcutaneously three times a week, followed by interferon-alpha monotherapy at
      the same dose for another 26 weeks. After treatment patients were observed for a
      further 26 weeks. Endpoints were a normalization of alanine aminotransferase and
      negativity of HBV DNA at weeks 52 and 78, as well as an improvement in liver
      histology at week 78. RESULTS: Eighteen (87.7%) of the 21 patients responded by
      losing serum HBV DNA and normalizing alanine aminotransferase values at the end
      of the 52-week treatment period. Sixteen (76.2%) of these patients became
      sustained responders, with normal alanine aminotransferase and negative HBV DNA
      at the end of 78 weeks. Two patients were non-responders, two relapsed and one
      had a breakthrough during therapy. Significant improvements in the Knodell
      histological activity index were observed in the responders. No adverse events
      other than those seen previously with interferon monotherapy were reported.
      CONCLUSIONS: Combination interferon-alpha 2b and thymosin-alpha 1 treatment may
      provide a safe and effective therapeutic approach for the difficult-to-treat anti
      HBe-positive chronic hepatitis B patients. Further controlled studies are needed
      to assess the full role of this treatment strategy.

PMID- 12063994
TI  - Laparoscopic hepatectomy for benign liver tumors.
AB  - We describe our initial experience with videolaparoscopic hepatectomies. From
      November 1997 to May 1999, 6 female patients whose ages ranged from 36 to 71
      years with hepatic benign tumors were submitted to laparoscopic hepatectomy.
      Three patients had hepatic adenomas, 1 non-parasitic cyst, 1 focal nodular
      hyperplasia and 1 hemangioma. The laparoscopy was performed under general
      anesthesia with a pneumoperitoneum of carbonic gas. The following were used: 0
      degree and 30 degrees optics, 5, 10 e 12-mm trochars, a ring forceps, dissecting
      forceps, simple grasping forceps, curved scissors, mono- and bipolar cautery,
      endoscopic clip and vascular stapler. No ultrasonic scalpel or argonium
      coagulation were used. The surgical specimens were removed through a Pfannenstiel
      incision around 4-5 cm long, for a better anatomopathological evaluation. The
      surgical time ranged from 3 hours to 4 hours and 30 minutes. One patient had a
      prolonged ileus during the immediate postoperative period. Only a single patient
      had an abdominal drain. The time of hospitalization ranged from 2 to 7 days. No
      complications were observed in relation to the pneumoperitoneum. No deaths
      occurred in this series. In this way, laparoscopic hepatectomy may be an
      alternative approach in carefully selected patients.

PMID- 12063995
TI  - The separate-lesion type combined hepatocellular carcinoma and
      cholangiocarcinoma.
AB  - The separate-lesion type of combined hepatocellular carcinoma and
      cholangiocarcinoma is particularly rare. We treated two such patients with
      hepatic resection after performing dynamic computed tomography. In case 1, a 64
      year-old Japanese man with chronic hepatitis C underwent right hepatic lobectomy
      for two hepatic tumors; both tumors originally were thought to be hepatocellular
      carcinomas because both were hypervascular. However, histologic examination
      revealed that one tumor was hepatocellular carcinoma and another tumor was
      tubular adenocarcinoma. In case 2, a 73-year-old man, a second lesion was
      detected 8 months after transcatheter arterial embolization for hepatocellular
      carcinoma associated with chronic hepatitis C. The newer lesion in case 2 showed
      delayed enhancement by dynamic computed tomography. We diagnosed the lesion as
      cholangiocarcinoma and performed right hepatic lobectomy and dissection of lymph
      nodes in the hepatoduodenal ligament. Histologic examination confirmed that the
      new lesion was tubular adenocarcinoma. Case 1 and 2 respectively represent
      synchronous and metachronous occurrence of the separate-lesion variety of
      combined hepatic cancer.

PMID- 12063996
TI  - Pseudo-Budd-Chiari Syndrome: decompensated alcoholic liver disease mimicking
      hepatic venous outflow obstruction.
AB  - Three patients with rapid onset decompensated liver disease who were referred to
      our hospital with presumed Budd-Chiari syndrome are described. This diagnosis was
      based on marked hepatomegaly, caudate lobe hypertrophy and failure to visualize
      hepatic veins by Doppler-ultrasound examination. Detailed history, biochemistry,
      and histology were, however, highly suggestive of alcoholic liver cirrhosis with
      steatohepatitis-induced hepatomegaly. On angiographic examination narrowed but
      patent hepatic veins were demonstrated in 2 patients. A third patient died before
      further work-up could be performed; autopsy showed patent hepatic veins. These
      cases show that the radiological diagnosis of Budd-Chiari syndrome due to hepatic
      vein obstruction can be false positive and that suspected hepatic vein occlusion
      on Doppler-ultrasound should be confirmed by angiographic studies and on liver
      histology.

PMID- 12063997
TI  - Quality of life assessment in chronic liver disease.
AB  - The evaluation of quality of life in chronic liver disease is a crucial outcome
      measure of all interventions on patients. This paper presents a variety of
      clinical situations in which it is essential to assess quality of life: in fact,
      chronic liver disease ranges from asymptomatic B or C hepatitis to liver failure
      and transplantation. It also points out some methodological pitfalls: in
      particular, the choice of validated questionnaires, the use of generic
      instruments versus specific ones, timing of administration, choice of cross
      sectional versus longitudinal studies, control of bias (selection and attrition)
      and other relevant methodological issues.

PMID- 12063998
TI  - Monitoring hepatic venous hemoglobin oxygen saturation during Appleby operation
      for pancreatic cancer.
AB  - BACKGROUND/AIMS: When an Appleby operation is performed for pancreatic body and
      tail carcinoma, it is necessary for prevention of hepatic ischemia to estimate
      accurately the hepatic circulation after resection of the celiac artery, the
      common hepatic artery and the portal vein. We studied the hepatic circulation by
      monitoring the ShvO2 (hepatic venous hemoglobin oxygen saturation) during an
      Appleby operation. METHODOLOGY: We performed an Appleby operation on 8 patients
      with pancreatic cancer. In 6 of 8 patients, a 7-Fr fiberoptic flow direct
      catheter was inserted in the right hepatic vein. The ShvO2 values were monitored
      continuously during surgery. RESULTS: The ShvO2 value was 76 +/- 3.5% just after
      laparotomy, and reduced to 61 +/- 13.2% after clamping the common hepatic artery.
      The values of the ShvO2 returned to 70.8 +/- 10.9% one hour after clamping. But,
      one patient underwent reconstruction of the common hepatic artery, because the
      ShvO2 value still stood at 50%. Combined resection of the portal vein was
      performed in 5 out of 8 patients. Two patients underwent resection of the portal
      vein without reconstruction due to the development of the collateral vein, one
      patients; resection of the portal vein with reconstruction, and two patients;
      wedge resection. In all 5 patients, the ShvO2 was stable during resection of the
      portal vein. CONCLUSIONS: Monitoring the ShvO2 is a useful method to evaluate at
      real time the hepatic circulation during the Appleby operation, and to decide if
      reconstruction of the common hepatic artery or the portal vein is needed or not.

PMID- 12063999
TI  - Effect of intravenous infusion of amino acids on pancreatic secretion.
AB  - BACKGROUND/AIMS: The effect of intravenous administration of amino acids on
      exocrine pancreatic secretion is controversial. Since amino acids are used in
      parenteral nutrition of patients with acute pancreatitis or other pancreatic
      diseases, it seemed useful to establish whether or not they affect pancreatic
      secretion. METHODOLOGY: Four patients having an external transduodenal drainage
      of the main pancreatic duct performed after sphincteroplasty for common bile duct
      stones were studied. Two of them had undergone a Billroth II gastrectomy in the
      past. Pancreatic secretion was stimulated with low doses of secretin (0.1
      CU/kg/h) and cerulein (10 ng/kg/h); after 75 min of stimulation, when pancreatic
      secretion was stable, a solution of L-amino acids (Freamine III 8.5%) was infused
      intravenously at a rate of 150 mL/h, for two hours. The volume of pancreatic
      secretion, bicarbonate and total protein was measured. RESULTS: The infusion of
      amino acids did not cause significant changes in pancreatic secretion. However,
      considering the results individually, they caused a clear increase of pancreatic
      secretion, mainly of bicarbonates (mean increase of 36%) in the two subjects who
      had not undergone previous surgical procedures and no increase in the two who had
      had a Billroth II gastrectomy. CONCLUSIONS: The results suggest that intravenous
      administration of amino acids stimulates exocrine pancreatic secretion in normal
      subjects but not in those who underwent previous gastrectomy. This stimulatory
      effect could be mediated by stimulation of gastric acid. This effect should be
      taken into consideration when amino acids are used in patients with acute
      pancreatitis or other pancreatic disorders.

PMID- 12064000
TI  - The peculiar processing of glucagon and glucagon-related peptides in patients
      after pancreatectomy.
AB  - BACKGROUND/AIMS: Although, glucagon has been detected even in the serum of
      totally pancreatectomized patients and the origin was suggested to be the
      intestine, the kinetics of glucagon is not well known after pancreatectomy. In
      this study, we investigated the kinetics of glucagon and glucagon-related
      peptides and discuss the glucagon processes in the pancreas and intestine in
      pancreatectomy patients. METHODOLOGY: Seven patients who had undergone
      pancreatoduodenectomy reconstruction using Child's procedures (distal
      pancreatojejunostomy, choledochojejunostomy and gastrojejunostomy) (group PD) and
      five patients who had undergone distal pancreatectomy (group DP) served as the
      subjects of this study. In addition to these two groups, five patients who had
      undergone gastrectomy reconstructions using the Billroth II procedure (group GX),
      to examine whether the alimentary tract reconstructions themselves would have any
      effect on the kinetics of glucagon, and 10 normal subjects (group C) were also
      enrolled in this study. All patients received a 75-g oral glucose tolerance test
      in the early morning fasting state. Serum glucagon levels were assessed using the
      glucagon non-specific N-terminal (glucagon-like immunoreactivity: GLI) and
      specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The
      molecular forms of these glucagon-related peptides were also estimated using the
      gel filtration chromatography method before and after the 75-g oral glucose load.
      RESULTS: After the glucose load, serum GLIs were increased significantly in
      groups GX and PD suggesting that these were affected by the alimentary tract
      reconstructions. Serum IRGs including true pancreatic glucagon were slightly
      increased in groups PD and DP after oral glucose load suggesting that these
      paradoxical responses might be associated with the glucose tolerance deficiencies
      observed in both groups, but not associated with the alimentary tract
      reconstruction. CONCLUSIONS: The paradoxical rise of IRGs based on the findings
      of gel filtration chromatography were possibly due to the generated peculiar
      glicentin-like peptide and pancreatic glucagon from the glucagon precursor,
      preproglucagon, after pancreatectomy, which is processed in association with the
      glucose tolerance deficiencies after pancreatectomy.

PMID- 12064001
TI  - The effects of somatostatin on the microperfusion of the pancreas during acute
      necrotizing pancreatitis in rats.
AB  - BACKGROUND/AIMS: Autodigestion and impairment of microcirculation of the pancreas
      play an important role in the pathogenesis of acute pancreatitis. Somatostatin
      with the reducing effect on the hepato-splanchnic blood flow decreases exocrine
      pancreatic secretion. Microcirculatory changes are central to the pathogenesis of
      acute pancreatitis. However, little is known about the effects of somatostatin on
      the pancreatic tissue oxygen pressure and acinar cell injury during acute
      pancreatitis. The aim was to evaluate somatostatin by measuring its effect on the
      pancreatic tissue oxygen pressure and acinar injury in acute pancreatitis.
      METHODOLOGY: Acute necrotizing pancreatitis was induced in rats by standardized
      intraductal bile acid infusion and cerulein hyperstimulation. Serum trypsinogen
      activation peptide was measured to verify comparable disease severity. After the
      induction of acute necrotizing pancreatitis, animals randomly received either
      ringer lactate or somatostatin. Monitoring included cardiorespiratory parameters,
      hematocrit, amylase, pancreatic tissue oxygen pressure, and trypsinogen
      activation peptide levels. At the end of the experiments the pancreas was removed
      for evaluation of acinar cell injury. RESULTS: The two study groups were
      comparable with regard to mean arterial pressure, heart rate, arterial blood
      gases, hematocrit, and serum amylase. The induction of pancreatitis resulted in
      the significant decrease of pancreatic tissue oxygen pressure in both groups. The
      use of somatostatin did not increase pancreatic tissue oxygen pressure. There
      were no significant differences in plasma trypsinogen activation peptide and
      serum amylase levels in the animals of two treatment groups. Only somatostatin
      decreased pancreatic damage significantly. CONCLUSIONS: The use of somatostatin
      did not improve pancreatic microcirculation or trypsinogen activation peptide
      level in acute necrotizing pancreatitis; however, it reduced pancreatic damage.
      Therefore, it has a limited value in the treatment of the acute pancreatitis.

PMID- 12064002
TI  - A case of intraductal papillary-mucinous carcinoma of the pancreas with the onset
      of acute pancreatitis.
AB  - Intraductal papillary-mucinous carcinoma of the pancreas has been reported with
      increasing frequency. We report a case with intraductal papillary-mucinous
      carcinoma of the pancreas and discuss surgical treatment and current imaging
      modalities. A case with intraductal papillary-mucinous carcinoma was analyzed by
      radiological findings and clinical course. A 47-year-old man developed abdominal
      pain and nausea. Computed tomography showed a diffusely dilated main pancreatic
      duct. Duodenoscopy showed a patulous orifice of the pancreas with massive mucus
      secretion, but the pancreatic juice was not positive for malignant cells.
      Endoscopic retrograde cholangiopancreatography revealed a markedly dilated
      pancreatic duct extending from the body to the tail of the pancreas. Distal
      pancreatectomy was performed with splenectomy and lymph nodes dissection.
      Histopathological diagnosis was intraductal papillary-mucinous carcinoma.
      Endoscopic retrograde cholangiopancreatography is useful for diagnosing
      intraductal papillary mucin-producing tumors. To avoid unnecessary total
      pancreatectomy and preserve pancreatic function, intraoperative frozen section
      examination is widely available for the surgical treatment of intraductal
      papillary mucin-producing tumors.

PMID- 12064003
TI  - Microcoils embolization of splenic artery pseudoaneurysm complicated with chronic
      pancreatitis.
AB  - Chronic pancreatitis is known to cause vascular complications including
      pseudoaneurysm of peripancreatic arteries that can lead to massive
      gastrointestinal bleeding. We report a 30-year-old man with splenic artery
      pseudoaneurysm formation secondary to chronic pancreatitis. The bleeding was
      successfully controlled by superselective microcoils embolization of the
      pseudoaneurysm with splenic preservation. The patient was discharged in 2 days
      with complete recovery. We consider superselective transcatheter embolization as
      one of the safest procedures and should be considered as a therapeutic option in
      the management of pseudoaneurysm caused by pancreatitis.

PMID- 12064004
TI  - Successful treatment of a T1 cancer of the pancreatic head with high dose rate
      brachytherapy and external radiotherapy.
AB  - In this report, a unique case of a localized (T1N0M0) adenocarcinoma of the head
      of the pancreas is presented, which was successfully treated with interstitial
      high dose rate brachytherapy combined with percutan irradiation after biopsy. A
      total dose of 18 Gy was delivered with brachytherapy (6 Gy per fraction on three
      consecutive days) to the tumor via after-loading catheter. Brachytherapy was
      followed by external radiotherapy, delivering an additional dose of 46 Gy (18 MV
      x) with four-field technique using conventional fractionation (2 Gy/day). Thirty
      six months after completion of the treatment the patient is alive with no
      evidence of disease. The combination of interstitial high dose rate brachytherapy
      and external beam radiation therapy may be an effective tool to deliver curative
      dose without any significant sequelae in the treatment of operable pancreatic
      carcinoma, when the patient's condition contraindicates surgery.

PMID- 12064005
TI  - Laparoscopic splenectomy for portal hypertension.
AB  - BACKGROUND/AIMS: Laparoscopic splenectomy is now increasingly being performed.
      However, controversy remains regarding the effectiveness of a laparoscopic
      splenectomy for patients with portal hypertension. METHODOLOGY: Seventy-three
      patients with portal hypertension who underwent a laparoscopic splenectomy from
      February 1992 until October 2000 were reviewed and the effectiveness of the
      procedures for portal hypertension was evaluated. Forty-two patients had
      esophagogastric varices and twenty had a concomitant hepatocellular carcinoma.
      The indications for surgery were bleeding tendency due to thrombocytopenia (n =
      40), difficulty in receiving treatment for hepatocellular carcinoma due to
      thrombocytopenia (n = 18), and sclerotherapy-resistant esophagogastric varices (n
      = 15). RESULTS: A laparoscopic splenectomy was successfully performed in all the
      patients. The rate of conversion to conventional open surgery was 9.6% (7/73).
      The mean operative time was 210.1 +/- 101.9 minutes, and the estimated blood loss
      was 374.7 +/- 352.4 mL. There were no cases of mortality, and morbidity was
      encountered in 11.0% of patients. The increase in the platelet count correlated
      significantly to the spleen weight (P < 0.001). The platelet count had been
      maintained at over 10 x 10(4)/mm3 for over three years. Eighteen patients with
      hepatocellular carcinoma successfully underwent treatment for hepatocellular
      carcinoma after surgery and no recurrence of esophagogastric varices was
      encountered. CONCLUSIONS: A laparoscopic splenectomy resulted in the successful
      secondary treatment of hepatocellular carcinoma and esophagogastric varices.
      Portal hypertension was not a contraindication. A laparoscopic approach is
      therefore the procedure of choice for a splenectomy in portal hypertension.

PMID- 12064006
TI  - An experimental study of jejunal pouch replacements following total gastrectomy.
AB  - BACKGROUND/AIMS: The nutritional effects of pouch replacement after total
      gastrectomy remain clinically controversial. Two previous experiments failed to
      show any nutritional benefit. However, the pouches applied clinically and
      examined experimentally so far were all of anti-peristaltic type. METHODOLOGY:
      Male 7- or 8-week-old Wistar rats were divided into 3 experimental groups after
      total gastrectomy. For group 1 and 2 rats, Roux-en-Y reconstructions and Hunt
      Lawrence pouches, i.e., anti-peristaltic type, were performed, respectively.
      Group 3 rats underwent a new type of iso-peristaltic pouch replacement. Food
      intake was recorded daily and all rats were weighed once a week. At the end of
      the 12-week experimental period, there were 9 rats in group 1, 10 in group 2, and
      8 in group 3. The volumes of the gastric reservoirs were measured, and blood
      samples were taken. Five 20-week-old rats served as control of weight, food
      intake, and laboratory data. RESULTS: The volumes of the gastric reservoirs in
      group 2 and 3 rats were significantly larger than in group 1 animals. However,
      there were no intergroup differences in weight change or food intake. The weights
      and the food intakes of the 3 experimental groups were significantly lower than
      those of the control rats. No superiority in the results of blood samples was
      observed among the experimental groups. Correlations between weight gain and food
      intake were shown in all groups. But, a correlation between the volume of the
      gastric reservoir and food intake was observed only for group 3 rats.
      CONCLUSIONS: The present study showed no nutritional benefits of an iso- as well
      as an anti-peristaltic pouch replacement.

PMID- 12064007
TI  - Immunodeficiency in radically operable gastric cancer patients.

PMID- 12064008
TI  - Reappraisal of the new UICC staging system for gastric cancer: problem in lymph
      node stage.
AB  - BACKGROUND/AIMS: The International Union Against Cancer (UICC) TNM staging system
      defined a new system for classifying gastric cancer, based on the number of
      metastatic nodes (1997). However, the advantage of the new system is still a
      matter of debate. The aim of the present study is to compare the new system with
      the old one (1987), which is based on the location of positive lymph nodes.
      METHODOLOGY: We analyzed the survival of 608 patients with curative resection of
      their gastric cancer. The average number of resected and involved lymph nodes for
      each resected patient was 31.4 and 7.7. Comparison of these two systems was
      carried out to determine which classification was more effective. The prognostic
      value of different lymph node staging systems was also analyzed. RESULTS: One
      hundred and thirty-five patients (22.2%) had different N classification and 109
      (17.9%) had different TNM staging. There was a significant stepwise decrease of
      slope of survival curve for each stage, but the new system did not cleanly
      separate stage II with IIIa at 3 years and stage IIIb with IV at 5 years.
      Although different lymph node staging systems were able to predict survival, the
      ratio rather than the number of involved nodes had a more cleanly separated
      stepwise decrease of slope of survival curve. CONCLUSIONS: The new UICC staging
      system is not better than the old system for the staging of gastric cancer. The
      reason is that the category of node number seems not to be appropriate and will
      be influenced by the extent of lymph node dissection. To overcome this problem,
      the frequency of involved nodes can be adopted instead of the number.

PMID- 12064009
TI  - Failed antireflux surgery: surgical outcome of laparoscopic refundoplication in
      the elderly.
AB  - BACKGROUND/AIMS: Antireflux surgery has a failure rate between 5 and 20%.
      Laparoscopic redo-surgery is feasible, but little is known about the surgical
      outcome in elderly patients. The aim of this prospective study was to evaluate
      early surgical experience and outcome, including quality of life, after
      laparoscopic refundoplication in patients older than 65 years. METHODOLOGY:
      Eleven patients, mean age of 71 years (range: 65-78), underwent laparoscopic redo
      surgery. Six patients had the former antireflux procedure performed by the open
      technique, one having had it twice, one had both laparoscopic and open antireflux
      procedures, and in 4 the primary intervention was performed laparoscopically.
      Quality of life was evaluated by using the Gastrointestinal Quality of Life
      Index. All patients were evaluated prior to surgery, and at 3 months and 12
      months after laparoscopic refundoplication, as well as with esophageal manometry
      and 24-hour pH-monitoring. RESULTS: Redo-procedures were completed
      laparoscopically in 10 patients. In one patient conversion to an open laparotomy
      was necessary because of severe bleeding from the spleen. One patient had an
      injury to the gastric wall, successfully managed laparoscopically.
      Postoperatively, one patient had moderate dysphagia for a period of two months,
      another had epigastric pain for the same period. Esophageal manometry and 24-hour
      pH-monitoring showed normal values in all patients after redo-surgery. Prior to
      redo-surgery, the mean Gastrointestinal Quality of Life Index was 85.2 points.
      Three months (mean: 119.8 points) and one year (mean: 119.2 points) after
      laparoscopic reoperation the general score increased significantly (P < 0.01) and
      attained the equivalent level of comparable healthy individuals (118.7 points).
      CONCLUSIONS: Laparoscopic refundoplication in the elderly patient is feasible,
      safe and an effective treatment after failed antireflux surgery. Older patients
      with failed antireflux surgery have poor quality of life. Laparoscopic redo
      surgery improves quality of life significantly to the level of healthy
      individuals and normalizes objective outcome criteria without any long-term
      restrictions in daily life.

PMID- 12064010
TI  - Cell proliferation, apoptosis and angiogenesis in gastric cancer and its hepatic
      metastases.
AB  - BACKGROUND/AIMS: The levels of cell proliferation, apoptosis and angiogenesis
      were compared histochemically in gastric cancer and its hepatic metastases.
      METHODOLOGY: Tissue samples were taken from 7 patients with gastric cancer
      associated with synchronous and/or metachronous hepatic metastases. In the 7
      gastric cancers and in 4 synchronous and 4 metachronous hepatic metastases, Ki-67
      immunostaining was performed to measure the labeling index (Ki-67 LI). Terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end
      labeling was performed to measure the apoptotic index, and immunostaining for
      factor VIII-related antigen was performed to measure the microvessel density.
      RESULTS: The Ki-67 LI was higher in the gastric cancer and the metachronous
      hepatic metastasis than in the synchronous hepatic metastasis (primary lesions
      vs. synchronous foci vs. metachronous foci: 47.1% vs. 39.3% vs. 48.0%; P < 0.05).
      The apoptotic index was lower in the gastric cancer and the metachronous hepatic
      metastasis than in the synchronous hepatic metastasis (3.50% vs. 5.01% vs. 2.64%;
      P < 0.05). The microvessel density was higher in the gastric cancer and the
      metachronous hepatic metastasis than in the synchronous hepatic metastasis (36.0
      vs. 22.2 vs. 34.2; P < 0.05). CONCLUSIONS: The present results suggest that tumor
      growth as indicated by cell proliferation, apoptosis and angiogenesis is less
      vigorous in synchronous hepatic metastasis than in primary lesion and/or
      metachronous hepatic metastasis.

PMID- 12064011
TI  - Peritoneal carcinomatosis and lymph node metastasis are prognostic indicators in
      patients with Borrmann type IV gastric carcinoma.
AB  - BACKGROUND/AIMS: Having observed a lower survival rate of patients with Borrmann
      type IV gastric cancer, we attempted to determine its prognostic indicators.
      METHODOLOGY: A total of 103 patients with Borrmann type IV gastric cancer were
      evaluated; 604 patients with Borrmann types I, II and III were used as
      references. RESULTS: The results showed that Borrmann type IV gastric cancer were
      larger, had deeper invasion, more lymphatic and vascular invasions, predominant
      diffuse type and scirrhous stromal reaction, extensive lymph node metastases and
      peritoneal carcinomatosis. The 5-year survival rate (11.3%) was significantly
      lower than that of others (44.7%, P < 0.001). Univariate and multivariate
      analyses of survival showed that peritoneal carcinomatosis and lymph node
      metastasis were independently associated with a relative risk of 1.8 and 1.4,
      respectively. The survival rates of 46 patients with potential curative disease
      were similar, regardless of various extents of resection. CONCLUSIONS: Peritoneal
      carcinomatosis and lymph node metastases are prognostic indicators in patients
      with Borrmann type IV gastric cancer. Optimal surgical strategy for Borrmann type
      IV gastric cancer remains unclear.

PMID- 12064013
TI  - Correlation between expression levels of thymidine phosphorylase (dThdPase) and
      clinical features in human gastric carcinoma.
AB  - BACKGROUND/AIMS: dThdPase (thymidine phosphorylase) is an enzyme that is involved
      in pyrimidine nucleoside metabolism. It has been recently reported that dThdPase
      is identical to platelet-derived endothelial cell growth factor. Previous studies
      demonstrated that the immunohistochemical expression of dThdPase was related with
      disease progression. The purpose of this study was to examine the expression
      levels of dThdPase and their prognostic significance in gastric carcinoma,
      prospectively. METHODOLOGY: We obtained fresh samples (tumors and adjacent normal
      mucosa) from 263 patients with gastric cancer who underwent gastrectomy between
      April 1998 and March 2000. dThdPase was analyzed by the enzyme-linked
      immunosorbent assay method. RESULTS: The expression levels of dThdPase in tumors
      (98.4 +/- 62.5 U/mg protein) was significantly higher than that in normal mucosa
      (46.5 +/- 27.8 U/mg protein) (P < 0.0001). Intratumoral dThdPase levels were
      significantly higher in Borrmann types II and III macroscopically (P < 0.01), in
      poorly differentiated type histologically (P < 0.05), and in the tumor-invading
      serosa (P < 0.001). The expression levels of dThdPase were also significantly
      higher in tumor tissue from patients with lymph node metastasis (P < 0.01) and in
      that from patients with lymphatic invasion (P < 0.05). The survival rate of
      patients with tumor of high dThdPase (> or = 100 U/mg protein) was significantly
      poorer than that of patients with tumor of low dThdPase (< 100 U/mg protein) (P <
      0.05). CONCLUSIONS: These findings indicate that the measurement of dThdPase may
      provide useful information for predicting prognosis in gastric carcinomas.

PMID- 12064012
TI  - Histological and clinical predictive value of determination of tissue CagA status
      by PCR in Helicobacter pylori infected patients; results of the large population
      based study in western Turkey.
AB  - BACKGROUND/AIMS: Early experimental and epidemiological studies have suggested
      that the presence of cagA gene was a virulence factor for Helicobacter pylori. We
      aimed to investigate the clinical significance of tissue CagA status in
      Helicobacter pylori infected patients and to assess its association with
      histological changes in gastric mucosa. METHODOLOGY: Three hundred and forty-five
      patients with Helicobacter pylori infection established by both urease test and
      histological examination were included in the study. The symptoms of the patients
      were recorded according to the Glasgow dyspepsia scale. Biopsies (cardia, corpus,
      angulus and antrum) were evaluated histologically according to the Sidney system.
      The cagA status was determined by polymerase chain reaction method from an antral
      biopsy. Polymerase chain reaction studies were performed by Wizard genomic DNA
      purification system (promega). We also determined the serum levels of tumor
      necrosis factor-alpha, and gastrin. They were all prescribed lansoprazole (30 mg
      b.i.d.), clarithromycin (500 mg b.i.d.), and amoxycillin (1 g b.i.d.) for a week.
      At the 8th week a second endoscopy was performed and further biopsy specimens
      were obtained from the same sites. Mann-Whitney U and chi 2 tests were used for
      statistical analyses. RESULTS: Two hundred and thirty-five patients (68.1%) were
      infected with cagA-positive strains of Helicobacter pylori and the other 110
      patients (31.8%) were infected with cagA-negative strains. We compared the
      parameters and measurements studied in this trial between the patients infected
      with cagA-positive and negative Helicobacter pylori strains. Helicobacter pylori
      density was greater in the cagA-positive group by 1.9 +/- 0.9 than in the cagA
      negative group by 1.2 +/- 0.7 (P = 0.01). Helicobacter pylori activity and
      chronic inflammation also were significantly higher in the cagA-positive group
      with the values of 1.4 +/- 0.8 and 2.1 +/- 1.1 than in the cagA-negative group
      with 0.7 +/- 0.2 and 1.3 +/- 0.5, respectively (P = 0.001, P = 0.002). The
      presence of atrophy and lymphoid aggregate was not different between the two
      groups (P > 0.05). However intestinal metaplasia was shown to be significantly
      frequent in patients infected with cagA-positive Helicobacter pylori strains
      (0.001). Serum tumor necrosis factor-alpha and gastrin levels which were accepted
      as the markers of inflammation in Helicobacter pylori infection were increased in
      the cagA-positive group compared with the cagA-negative group. Serum tumor
      necrosis factor-alpha level was 11.3 +/- 7.0 pg/mL in the cagA-positive group and
      4.9 +/- 2.7 pg/mL in the cagA-negative group (P = 0.001). Gastrin level also
      showed a significant difference between two groups by 66.8 +/- 31.1 pg/mL and
      37.2 +/- 19.2 pg/mL, respectively, in the cagA-positive and negative groups (P =
      0.001). The virulent strains seem to cause peptic ulcer more frequently. Peptic
      ulcer was determined in 17% of patients in the cagA-positive group but this ratio
      was 9% in the cagA-negative group (P = 0.608). Although, all these differences of
      the degree of inflammation, clinical spectrum and biochemical parameters were
      seen, interestingly there was no significant difference in the severity of the
      symptoms of the patients in both groups according to Glasgow dyspepsia severity
      score (P = 0.20). CONCLUSIONS: Our results confirm that cagA-positive strains of
      Helicobacter pylori cause greater histological changes. However this virulence is
      not associated with more severe symptoms. The histological changes can be
      predictable by determining the tissue cagA status.

PMID- 12064014
TI  - The formulated growth of early gastric cancer.
AB  - Although the proportion of early gastric cancer is rising in the incidence of
      gastric cancer as a whole, its natural history is still under discussion. We
      report a patient who was diagnosed with early gastric cancer and who had
      undergone barium studies once a year for the three previous years. The exact,
      increasing size of the tumor could be measured at these four time points, and the
      data show, almost exactly, the line calculated by the formula S = 0.3 t2 [S =
      size (cm2) of the cancerous lesion, t = time (yr) elapsed from the beginning of
      the gastric cancer].

PMID- 12064016
TI  - Validity: what, why, and how.

PMID- 12064015
TI  - Tenofovir disoproxil fumarate (Viread).
AB  - Treatment Review is intended to inform and update nurses about treatments
      relevant to HIV/AIDS. Product information presented in this column does not imply
      endorsement by the Association of Nurses in AIDS Care.

PMID- 12064018
TI  - HIV and pregnancy: tough choices ... and the right to choose.

PMID- 12064017
TI  - Encouraging resistance data for Kaletra (lopinavir/ritonavir).

PMID- 12064019
TI  - The other side of the pill bottle: the lived experience of HIV-positive nurses on
      HIV combination drug therapy.
AB  - A qualitative study of nine HIV-positive nurses was conducted to explore the
      experience of daily life for HIV-positive nurses taking HIV combination drug
      therapy. The purpose of the study was to gain a better understanding of factors
      relating to HIV medication adherence and nonadherence. The study also provided
      new knowledge on what it is like to be a nurse who is HIV-positive.
      Implementation of the study and analysis of the data were done using an
      integrated method for conducting phenomenological research. Face-to-face in-depth
      interviews were conducted around the United States with three women and six men
      who were HIV-positive nurses. Participants had acquired HIV via three modes:
      occupational exposure, sexual transmission, and contaminated blood products. The
      nurses were taking HIV antiretroviral medications in various combinations.
      Analysis of the nurses' interviews revealed six major themes that described the
      experience of day-to-day life for HIV-positive nurses on HIV combination drug
      therapy. The metaphor that emerged across the narratives was the Double-Edged
      Sword of Being a Nurse on the Other Side, in the role of patient. The metaphor
      described the life-changing experience of being an HIV-positive nurse attempting
      to adhere to the prescribed HIV combination drug regiment. While many of the
      study findings were congruent with the literature, new components of the
      experience emerged. The study gave voice to a group of nurses who previously have
      been described only in terms of HIV/AIDS statistics.

PMID- 12064020
TI  - Assessment of growth and immunologic function in HIV-infected and exposed
      children.
AB  - Many children who are HIV infected grow poorly. An epidemiological framework
      guided a retrospective chart review assessing growth in three groups of children
      (n = 192): (a) children who were HIV infected secondary to maternal transmission
      (n = 77), (b) children who had been HIV-positive at birth but became seronegative
      and continue to be observed (seroreverters) (n = 84), and (c) HIV-infected
      children who had died (n = 31). Growth failure in the HIV-infected children was
      significantly greater than that expected in the general population. The
      seroreverters also demonstrated significantly more growth failure than that
      expected in the general population. Of the children who had linear growth
      failure, only 3 of 12 HIV-infected children and 2 of 11 seroreverters also had
      inadequate weight gain. However, 13 of 15 children with growth failure who
      subsequently died had poor weight gain. HIV classification was not significantly
      related to growth. These findings extend our understanding to a large, urban
      population of children in the United States including those who are older than
      children in other studies and who developed HIV through perinatal transmission.
      Nursing clinical practice and research implications are offered.

PMID- 12064021
TI  - Differentiation and treatment of anemia in HIV disease.
AB  - Anemia is a frequent complication of HIV disease that contributes to decreased
      quality of life and increased morbidity and mortality. The three major categories
      of anemia in HIV disease are anemia due to impaired red blood cell production,
      anemia due to increased red blood cell destruction, and anemia due to increased
      red blood cell loss. Although anemia of chronic illness is the most common type
      of anemia in HIV disease, other classifications of anemia may be encountered.
      Understanding the pathophysiology of anemia and laboratory tests that are
      frequently used to establish the differential diagnosis of anemia helps to ensure
      that HIV-infected individuals will receive appropriate treatment.

PMID- 12064023
TI  - Clinical aromatherapy and AIDS.
AB  - Clinical aromatherapy is the use of essential oils for expected outcomes that are
      measurable and is a therapy that is used as part of nursing care in Switzerland,
      Germany, Australia, Canada, the United Kingdom, and, more recently, the United
      States. Essential oils are steam distillates obtained from aromatic plants. These
      volatile extracts have been used for many years by French hospitals against
      airborne bacteria and fungi. As antimicrobial agents, essential oils may be
      appropriate in HIV/AIDS for specific opportunistic infections. Aromatherapy can
      also alter perceptions of chronic pain, help maintain skin integrity, and is
      useful in stress management. Methods of application vary depending on the site of
      infection and the psychological profile of the patient and can include
      inhalation, compresses, baths, massage, and the "m" technique. This article will
      explore the potential use of essential oils in HIV/AIDS focusing on four
      opportunistic infections: Cryptococcus neoformans, Candida albicans, methicillin
      resistant Staphylococcus aureus, and herpes simplex types I and II.

PMID- 12064022
TI  - Inner strength among HIV-infected women: nurses can make a difference.
AB  - The purpose of this qualitative study was twofold. First, the authors examined
      the phenomenon of inner strength as a resource that women infected with HIV use
      to cope with and manage their difficult lives. Second, the authors sought the
      women's views on the potential impact health care workers, specifically nurses,
      can have on the activation of inner strength. This study was phenomenologically
      informed and qualitatively structured. The goal was to construct an analytical
      understanding of inner strength as it is perceived, defined, experienced, and
      activated by women infected with HIV. Data were collected by means of 19
      conversational, biographical interviews. These interviews were conducted with a
      stratified (by ethnicity and social class) sample of women infected with HIV. The
      data were elicited in terms of respondents' stories of living with HIV. The women
      listed a number of definitions for inner strength such as "the ability to fight"
      and "the motivation to go on and do better." The women recommended that nurses
      working with them be sensitive to the following patient concerns: validation,
      reality, sensitivity, and autonomy. The concept of inner strength can be of great
      scholarly and clinical value if it is defined as follows: Inner strength refers
      to the different ways women with serious illnesses experience and talk about the
      deepest, existential resources available to and used by them to manage severe
      risks to self-integrity. The recommendations, although somewhat critical of
      nurses, are plausible because they incorporate nurses' traditional approaches to
      caring for patients.

PMID- 12064024
TI  - Forum on intervocalic consonants in phonological development.
AB  - Intervocalic consonants have received far less attention in research on first
      language acquisition than consonants at the edges of words. Theories have
      predicted that intervocalic consonants may show special properties because they
      are in a special position in syllable structure (constituting both an onset, or
      syllable-initial consonant, and a coda, or syllable-final consonant) or because
      they are in a special environment (between vowels). This editorial provides an
      overview of the issues, a review of the acquisition literature on the subject,
      and an introduction to the five papers in this special volume.

PMID- 12064025
TI  - Intervocalic consonants in the speech of typically developing children: emergence
      and early use.
AB  - The purpose of this paper is to present data on the development of intervocalic
      consonants in the first 2 years of life. The data address three different periods
      in the production of intervocalic consonants: babble, first words, and words from
      21-24 months. The focus of analysis for all three data sets is on the phonetic
      properties of consonants in intervocalic position, and on comparisons of
      inventories across word-initial, intervocalic, and final position. For word
      productions, intervocalic inventories are compared to inventories for initial and
      final positions. Results of all three studies indicate that intervocalic
      consonants closely resemble initial consonants in terms of frequency of
      occurrence and phonetic features.

PMID- 12064026
TI  - Intervocalic consonants in the acquisition of German: onsets, codas or something
      else?
AB  - This study examines the behaviour of five phonemes /f, [symbol: see text], ts, k,
      l/ in word-initial, word-final, and intervocalic positions in the productions of
      five German-speaking children (age 1;3 to 3;3 years) in order to determine the
      patterning of those intervocalic consonants--do they behave more like onsets or
      codas? The study also contrasts the behaviour of intervocalic consonants after
      short versus long vowels in view of the stance taken in the theoretical
      literature that intervocalic consonants after short vowels are ambisyllabic but
      not after long vowels. Findings show that out of 25 conditions (5 phonemes x 5
      children), nine yield support for the patterning of intervocalic consonants as
      codas, two as onsets, and five as unique (neither coda nor onset). Three
      conditions yield support for the dual patterning of intervocalic consonants. In
      all other conditions, there was insufficient information to support their
      patterning with codas or with onsets. Results provide minimal support for
      different patterns of intervocalic consonants after short and long vowels;
      however, the lengthening and insertion of consonants after short vowels suggest
      that children are aware of the different phonological roles of intervocalic
      consonants after short and long vowels.

PMID- 12064027
TI  - The influence of syllable position on children's production of consonants.
AB  - Two studies examined consonant production by 13 children with delayed
      phonological skills. Study 1 examined patterns of substitution errors in word
      initial, word-final and intervocalic positions of two-syllable words with a
      strong-weak stress pattern. For phonemes that were misarticulated in at least one
      word position, intervocalic consonant production was most likely to be the same
      as the word-final consonant production, but different from the word-initial
      consonant production. Study 2 examined proportions of matches and mismatches for
      features in five positions of multisyllabic words: (1) syllable-initial, word
      initial, (2) syllable-initial, within-word, (3) intervocalic before an unstressed
      syllable, (4) syllable-final, within-word, and (5) syllable-final, word-final.
      Significant variations in match ratios were observed as a function of syllable
      position. A number of different patterns of position-dependent errors were
      observed.

PMID- 12064029
TI  - The acquisition of medial /t, d/ allophones in bisyllabic contexts.
AB  - The acquisition of medial /t, d/ allophones was examined in four children between
      2 and 5 years of age, over a period of 38 months. Children labelled pictures
      designed to elicit a sample of these allophones in iambic ([t]) and trochaic
      (flap, nasal and lateral release) contexts. Productions were analysed with
      reference to attainment of target allophones and use of non-target segmental
      (e.g., [d] or [t] in place of flap) and syllabic variants (e.g., unstressed
      syllable deletion). All children produced the target [t] allophone in iambic
      context. Across children, between 10 and 15 variants occurred in trochaic
      contexts. Nasal and lateral release allophones were never attained. Flap
      attainment was variable, with significant differences across children and across
      phonetic contexts. Results suggest a hierarchy of /t, d/ allophone production
      with reference to prosodic and phonetic contexts. Discussion includes
      implications of these findings for clinical intervention.

PMID- 12064028
TI  - Intervocalic consonants in the speech of English-speaking Canadian children with
      phonological disorders.
AB  - Acquisition of intervocalic consonants has been insufficiently studied, both in
      terms of subject numbers, and in terms of differentiating syllabification
      patterns from those involving vowel feature assimilation. The question has
      remained: are English intervocalic consonants syllable-initial (onsets), syllable
      final (codas) or ambisyllabic? This study addresses these issues in the speech of
      44 English-speaking Canadian children with phonological disorders. Intervocalic
      consonants resembled word-initial onsets in that they were deleted less often
      than word-final consonants. When there was no deletion, intervocalic consonants
      were more likely to be segmentally unique (ambisyllabic?) than like onsets or
      codas. In segmental inventories, segments rarely appeared only in intervocalic
      position, and showed an equal affinity to onsets and codas, with two exceptions.
      Sonorant continuants and, to a lesser extent, fricatives showed patterns in
      intervocalic position that may have reflected assimilation. For children with
      less severe disorders, velars and fricatives occurred intervocalically only if
      they also occurred in codas, suggesting a coda-like (ambisyllabic?) status.

PMID- 12064030
TI  - A Streetcar Named Desire--psychoanalytic perspectives.
AB  - Tennessee Williams expressed in A Streetcar Named Desire aspects of his own
      psychic conflict that erupted after he reached sudden success with the play's
      predecessor The Glass Menagerie. Interpretations are suggested about those
      psychic conflicts and their emotional and behavioral manifestations through an
      analysis of both the play and the author's life history. In particular, the
      playwright's childhood experiences within a troubled family, his painful
      relationships with a rejecting, abusive father and an unhappy, controlling
      mother, and his helpless witnessing of the suffering inflicted upon his beloved
      sister are linked to the contrasting themes, characters, and action in both
      dramas.

PMID- 12064031
TI  - The object and the dream: Mark Rothko.
AB  - An exploration of unconscious determinants provides useful insights in
      considering Mark Rothko's creativity and behavioral characteristics. A basic
      focus is the issue of childhood loss and unresolved grief. The studies of Martha
      Wolfenstein on preadolescent and childhood parent loss are paramount in
      considering Rothko the man. Rothko, as a result of early losses, was predisposed
      to recurrent depressions and bouts of anger which created difficulties in his
      intimate relationships. Rothko evidenced a lifelong mistrust of male authority
      figures which may also account for his antipathy toward psychoanalysis. His
      psychological life was complicated by his experiences of institutionalized anti
      Semitism which further diminished his trust in others.

PMID- 12064032
TI  - Evidence-based psychotherapeutics.
AB  - Evidence-based medicine requires clinicians to base treatment of their patients
      on the findings of systematic clinical research. In recent years EBM has become
      linked with appropriate but also inappropriate efforts at cost containment.
      Organized psychiatry responded by developing evidence-based practice guidelines
      and launching a range of clinical research initiatives to determine the
      effectiveness and efficacy of current psychiatric practices. Psychoanalysis is
      particularly challenged because it has for most of the 20th century been based on
      conviction alone. Investigators have now identified the obstacles to research
      into psychoanalysis and dynamic psychotherapy and are developing techniques to
      overcome these and to study not only outcomes but also the internal processes of
      these treatment modalities. We may look forward to an evidence-based
      psychoanalysis in the 21st century.

PMID- 12064033
TI  - Gender differences in defensive style.
AB  - This study examines gender differences in defensive style across the domains of
      work and intimate relationships. Participants (47 women and 38 men) completed two
      versions (work-related; interpersonally related) of Bond's (1983) Defense Style
      Questionnaire (DSQ). Results showed that, while all participants use primarily
      mature defenses, they are significantly more likely to use immature defenses in
      love than at work; men are also significantly more likely than women to use
      immature defenses at work. In addition, women report significantly more use of
      intermediate defenses than men at work, while men report significantly more use
      of intermediate defenses than women in love. Results are discussed in light of
      Chodorow's (1978) theory of gender differences in development.

PMID- 12064034
TI  - On the Asclepian spirit and the future of psychoanalysis.
AB  - The dynamics of the Asclepian myth are analyzed, and generic dynamics of the
      healing imperative are illustrated. The story teaches much about the early
      theories and practice of ancient medicine, and originated the healing symbol of
      the staff and serpent which appears on the emblem of the American Academy. The
      multi-modal therapeutic approach used at the Asclepia was often climaxed by dream
      incubation as a centerpiece of the treatment. Dreams from modern physicians in
      analysis will be introduced to show that while our practice has changed in
      external trappings, the underlying dynamics of ancient and modern healers reflect
      a common humanity. Modern therapists have reacquired the use of dreams and
      invented a new set of explanatory myths. Consideration of future developments
      leads to linking the "psychosomatic model" of antiquity with the
      psychopharmacological interventions which are now common-place in psychodynamic
      psychotherapy. The Asclepian emphasis on spirituality is also finding increasing
      recognition among psychoanalysts and other scientists.

PMID- 12064035
TI  - From victim to heroine: children's stories revisited.
AB  - The need to escape reality and the taste for adventure with the unknown fills a
      universal need for both adults and children. Fairy tales have a powerful grip on
      the imagination because they are homespun versions of myths and have passionate
      intensity without epic grandeur. The happy ending of fairy tales reflects gender
      stereotyping because the heroine usually does very little except sit, wish, and
      wait for marriage. She has no control over her destiny and no active involvement
      in selecting or planning her future. These heroines are really passive victims.
      Sexism was once rampant in children's books. The Oz books, with their
      independent, courageous, and active heroine were way ahead of their time. The
      advent of women's liberation has led to a reappraisal of the female in folk
      literature. Anthropologists have now discovered stories of admirable women who
      were strong characters in their own epic dramas.

PMID- 12064036
TI  - Psychoanalytic peregrinations I: Transference and transference neurosis
      revisited.
AB  - The various meanings of transference and transference neurosis are reviewed with
      special attention to the various roles transference plays in the psychoanalytic
      process. A study of the provenance of transference is offered with some remarks
      on the crucial emphasis on understanding and interpreting the transference in
      psychoanalytic treatment. The danger of using other types of interventions as
      being manifestations of countertransference is suggested.

PMID- 12064037
TI  - Daniel Deronda and Gwendolen Harleth: a therapeutic relationship?
AB  - In Daniel Deronda, George Eliot presents Gwendolen as having been rescued by
      Daniel, and most commentators have agreed, with many comparing the relationship
      to that of patient and therapist. These commentators have allowed themselves to
      be unduly influenced by George Eliot's interpretations and judgments and have
      ignored the concrete depiction of her characters. While we are being told that
      Gwendolen is undergoing a conversion in which she develops a new consciousness, a
      new soul, we are being shown a character who is full of rage, self-hatred, and
      despair. Instead of leading her in the direction of psychological health, Deronda
      offers her his own defenses and fosters her dependency on him. Despite the upbeat
      tone of the ending, her prospects after he leaves England seem very bleak.

PMID- 12064038
TI  - Lasers in veterinary medicine--where have we been, and where are we going?
AB  - Future use of lasers in medicine depends on the active participation of
      veterinarians in the inception and development of new devices that meet the needs
      of the entire medical profession. The sensible clinical approach that must be
      taken every day in the practice of veterinary medicine equips the veterinarian
      with a unique ability to understand the practical applications of biomedical
      lasers. Veterinary medicine can and should be in the forefront during these
      exciting times, adding an essential dimension to development of this twenty-first
      century technology.

PMID- 12064039
TI  - Lasers and laser-tissue interaction.
AB  - Light produced by a laser differs from incandescent light in that it is
      monochromatic, coherent, and intense; and it is these properties that allow
      lasers to be used as such unique tools in biomedical research and patient care.
      The effect of a laser beam on tissue is dependent on the optical and mechanical
      properties of the tissue, and the wavelength, power parameters, and time domains
      of the laser exposure. Understanding these principles is not only important for
      the selection of an appropriate laser system for a specific application, but also
      is essential for that application to be successful.

PMID- 12064040
TI  - Laser safety.
AB  - Laser safety is a critical component in any laser surgery program. When used
      improperly, lasers have the potential to cause severe skin burns, induce corneal
      opacity and cataracts, damage the retina leading to blindness, and cause chronic
      respiratory diseases. For these reasons, each laser user is obligated to
      establish and comply with a laser safety program as outlined by ANSI.

PMID- 12064041
TI  - The economics of surgical laser technology in veterinary practice.
AB  - A decision to invest in and develop laser technology should only be made after a
      thorough investigation and comparison of the available types, vendors, available
      features, and purchasing options. A sound marketing program must then be used for
      introducing laser technology to the staff, clients, and colleagues. Without
      adhering to such a program, a practice will [figure: see text] not experience the
      necessary profitability following the purchase of a laser. Staff enthusiasm and
      support will dwindle, and ultimately the laser investment will be viewed
      unfavorably. When marketed properly, however, the investment in a surgical laser
      will provide outstanding profitability. The return on investment can be provided
      by using the support staff for client education, by offering laser technology for
      routine elective procedures and complex procedures, and by adhering strictly to a
      fee schedule. Add that to the truly remarkable results obtained using laser
      surgical techniques, a practice will be greatly enhanced.

PMID- 12064043
TI  - Feline onychectomy and elective procedures.
AB  - The development of the carbon dioxide (CO2) surgical laser has given
      veterinarians a new perspective in the field of surgery. Recently developed
      techniques and improvisations of established procedures have opened the field of
      surgery to infinite applications never before dreamed of as little as 10 years
      ago. Today's CO2 surgical laser is an adaptable, indispensable tool for the
      everyday veterinary practitioner. Its use is becoming a common occurrence in
      offices of veterinarians around the world.

PMID- 12064042
TI  - Soft tissue application of lasers.
AB  - Despite increasing numbers of veterinarians incorporating lasers into their
      clinical practices, little information has been published about laser clinical
      applications in soft tissue surgery. This article reviews soft tissue
      interaction, describes laser equipment and accessories commonly marketed to
      veterinarians, and discusses clinical applications of the carbon dioxide laser in
      a systems-based approach. A table of recommended laser tips and settings based on
      the authors' experiences using a carbon dioxide laser (AccuVet Novapulse LX-20SP,
      Bothell, WA) is provided.

PMID- 12064044
TI  - Use of the carbon dioxide laser for perianal and rectal surgery.
AB  - The skin of the perianal region is very thin and sensitive. The carbon dioxide
      laser is a very effective tool for removing tumors and treating conditions of
      this area. It offers a "no touch" method of treatment for conditions of the
      perianal region. There is less bleeding, less pain, less swelling with the use of
      the carbon dioxide laser. The carbon dioxide laser is an effective tool for
      excising perianal tumors, rectal tumors, performing anal sacculectomies and
      treating perianal fistulas.

PMID- 12064045
TI  - Diode laser and endoscopic laser surgery.
AB  - Two functionally important differences exist between the diode laser and the
      carbon dioxide (CO2) laser (used more commonly in small animal surgery). Diode
      laser energy is delivered through a quartz fiber instead of being reflected
      through an articulated arm or waveguide. Quartz fibers are generally more
      flexible and resilient than waveguides and can be inserted through an endoscope
      for minimally invasive procedures. Laser-tissue interaction is the other
      significant difference. The CO2 laser is completely absorbed by water, which
      limits the effect to visible tissue. The diode wavelength is minimally absorbed
      by water and may affect tissue as deep as 10 mm below the surface in the free
      beam mode. With proper respect for the tissue effect, these differences can be
      used to the advantage of the patient.

PMID- 12064046
TI  - Lasers in ophthalmology.
AB  - Laser technology continues to progress with the addition of new lasers, new
      delivery systems, and new applications. The introduction of lasers to veterinary
      ophthalmology has radically changed the level of care that we can provide to our
      patients. The development of the diode laser has particularly had an impact on
      veterinary ophthalmology. The diode's affordability, portability, and broad
      applications for veterinary patients have allowed laser surgery to become a
      routine part of veterinary ophthalmology practice. Educating the public and
      veterinary community in available laser techniques will generate improved
      ophthalmic care and provide more data on which to build future applications.

PMID- 12064047
TI  - Laser use in veterinary dentistry.
AB  - Lasers have been used in human dentistry since the 1960's. Lasers can provide a
      veterinary dentist access to difficult to reach areas with a relatively bloodless
      surgical field. Due to vaporization of nerve endings, human patients undergoing
      laser dental treatment reveal less pain compared to scalpel driven procedures.
      Dental applications for the commonly used lasers are discussed, as are special
      safety precautions. Many dental procedures enhanced by a carbon dioxide laser are
      covered. Future applications for the laser in veterinary dentistry are also
      discussed.

PMID- 12064048
TI  - Photodynamic therapy for companion animals with cancer.
AB  - Photodynamic therapy is an emerging form of cancer therapy in veterinary
      medicine, which capitalizes on a photochemical reaction to kill malignant cells.
      Photodynamic therapy has been used to successfully treat a variety of veterinary
      cancers, with documented efficacy similar to radiation therapy. However,
      equipment expense and availability of photosensitizer have limited the widespread
      use of photodynamic therapy by veterinarians.

PMID- 12064049
TI  - The use of surgical lasers in exotic and avian practice.
AB  - Use of diode laser energy with fiberoptic endoscopic delivery in exotic animal
      and avian practice offers a minimally invasive method for performing specific
      surgical procedures. Trauma and blood loss are minimized, but the absorption
      characteristics of the diode laser wavelengths (805/980 nm) must be considered to
      avoid potential postoperative complications due to collateral photothermal
      coagulative necrosis.

PMID- 12064050
TI  - The veterinary technician's role in laser surgery.
AB  - The use of surgical lasers in veterinary practice has grown significantly since
      1996. Many veterinarians have studied and implemented the basic physics and
      tissue didactics required to successfully incorporate a surgical laser program
      into their practice. The support role of the veterinary technician is crucial to
      ensuring an efficient, safe, and successful outcome of any surgical laser
      procedure. The technician's role may include practice management duties, client
      communication, and laser safety officer duties. Although there are a variety of
      lasers, the most common types used in veterinary practice are carbon dioxide
      (CO2) and diode. This article presents an overview of the veterinary technician's
      role as a key support person in ensuring a safe and positive outcome in the
      implementation of CO2 and diode lasers in a veterinary practice.

PMID- 12064051
TI  - Lasers in medicine and surgery. Introduction.

PMID- 12064052
TI  - Synthesis and calcium antagonist activity of new 1,4-dihydropyridines containing
      nitrobenzylimidazolyl substituent in guinea-pig ileal smooth muscle.
AB  - New alkyl ester analogues of nifedipine, in which the ortho-nitrophenyl group of
      position 4 is replaced by 1-(4-nitrobenzyl)-5-imidazolyl or 2-methylthio-1-(4
      nitrobenzyl)-5-imidazolyl substituent, were synthesized and evaluated as calcium
      channel antagonists using the electrically induced contraction of guinea-pig
      ileal longitudinal smooth muscle. Our results demonstrate that all compounds
      inhibited the contractile response of guinea-pig ileum to electrical stimulation
      and the IC50 value of the most potent compounds 6a and 6f were significantly
      lower than that of nifedipine. Therefore, they are more potent than nifedipine.

PMID- 12064054
TI  - In vitro studies on the transdermal formulation containing pentoxifylline
      microspheres with poly-L-lactide.
AB  - In this study, microspheres of Pentoxifylline (PTX) obtained with poly-L-lactide
      were investigated for drug-polymer ratios of 1:1, 1:5 and 1:10 and the HPLC
      results of PTX in the microspheres indicated that 1:5 drug-polymer ratio had the
      highest loading efficiency. For HPLC analysis acetonitrile-water (40:60) was
      selected as the mobile phase because it yielded the most favorable k' values.
      Retention times are 4.51 and 7.88 min. for PTX and internal standard
      (phanecetin), respectively. Calibration curves were linear (r2 > 0.999) in the
      range of 0.5-10 mg/ml with no significant difference from the origin. Then,
      matrix controlled transdermal systems containing plain drug or microspheres of
      drug were prepared. Carrageenan was chosen as a matrix polymer. In vitro release
      data of the formulations were evaluated kinetically. The results obtained
      indicate that PTX containing microspheres can be incorporated in carrageenan
      matrices to form a transdermal therapeutic system.

PMID- 12064053
TI  - Studies in release behavior of diltiazem HCl from matrix tablets containing
      (hydroxypropyl)methyl cellulose and xanthan gum.
AB  - (Hydroxypropyl)methyl cellulose and xanthan gum were used as hydrophilic
      matrixing agents for preparing modified release tablets of diltiazem HCl. The
      amount of (Hydroxypropyl)methyl cellulose and xanthan gum exhibited significant
      effect on drug release from the tablets prepared by direct compression technique.
      Xanthan gum showed a higher ability to retard the drug release than
      (Hydroxypropyl)methyl cellulose. A 2(2) + 1 factorial design was adopted to study
      the effect of amount of (Hydroxypropyl)methyl cellulose and xanthan gum on
      percent drug released in first hour (Y60) and the time required for 90% drug
      dissolution (t90). A response surface plot is generated for investigating the
      effect of the independent variables on t90. The tablets containing 90 mg
      diltiazem HCl, 45 mg (Hydroxypropyl)methyl cellulose and 45 mg xanthan gum showed
      drug release upto 12 h. The value of similarity factor, f2, for the selected
      batch was found to be 85.1 when the dissolution study was carried out in water or
      simulated gastric fluid, indicating pH independent drug dissolution. The selected
      batch also showed a comparable release profile with a market product (f2 = 60.2).
      Linear relationship was observed between percent drug released and degree of
      swelling. The kinetics of the drug release fitted well to the Hixson-Crowell
      equation. It can be concluded that by using a suitable blend of
      (Hydroxypropyl)methyl cellulose and xanthan gum desired modified drug release can
      be achieved.

PMID- 12064055
TI  - Synthesis and antimicrobial evaluation of new phenoxyacetamide derivatives.
AB  - New N-(5-methylisoxazol-3-yl)-2 or 3 or 4-(phenoxyacetamido)benzamides 6a-t were
      synthesized and tested for their in vitro antimicrobial activity against gram
      positive (Staphylococcus aureus ATCC 25923) and gram negative (Escherichia coli
      ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) bacteria as well as fungi
      (Candida albicans ATCC 10231, Candida tropicalis ATCC 13803 and Cryptococcus
      neoformans ATCC 90112). Compounds 6 were devoid of antibacterial as well as
      antifungal activities at maximum tested concentrations of 50 micrograms/ml for
      bacteria and 100 micrograms/ml for yeast.

PMID- 12064056
TI  - Applicational possibilities of linear and non-linear (polynomial) regressions and
      analysis of variance: kinetics of chloramphenicol.
AB  - The dependance of the content and microbiological activity of Chloramphenicol
      (active substance) at dissolution on time and on pH, as well as that of the
      content and microbiological activity of Chloramphenicol (250 mg capsules) at
      release, on time, in in-vitro conditions, was determined using linear and non
      linear (polynomial and generalized dilution) regressions. Based on the square
      error value, the dependance of the content and microbiological activity of
      Chloramphenicol (active substance) at dissolution on time and different pH
      values, as well as the dependance of the content and microbiological activity of
      Chloramphenicol (capsules) at release on time were best described by polynomial
      function. The comparison of the content and microbiological activity of
      Chloramphenicol (active substance) at dissolution at different pH values, as well
      as of Chloramphenicol (capsules) at release showed the significant correlation
      between these parameters (r = 0.999, P << 0.001). The comparision of the content,
      on one hand, and microbiological activity of Chloramphenicol (active substance),
      on the other, at dissolution at different pH values, as a function of time, was
      done using a modified method of one-way analysis of variance for linear
      regression comparisons. Based on the value of Fischer's coefficient (F), there is
      a statistically very significant difference between the contents and between the
      microbiological activities of chloramphenicol (active substance) at dissolution
      and different pH as a function of time (P << 0.005).

PMID- 12064057
TI  - Kinetic disposition of (+)-S- and (-)-R-sotalol enantiomers in cardiac patients
      with tachyarrhythmias using an improved HPLC-fluorescence stereoselective method.
AB  - Since the enantioselective pharmacokinetic profiles of R,S-sotalol in cardiac
      patients are controversial, the present investigation aimed to study the kinetic
      disposition of sotalol enantiomers in patients with tachycardia. Thirteen cardiac
      patients, who gave their written consent, were included (6F/7M; 53 +/- 12 yrs, 66
      +/- 13 kg, 163 +/- 8 cm height). They had tachycardia, normal renal function and
      had been chronically treated with tablets of sotalol 160 mg b.i.d. The patients
      were submitted to blood samples collection at zero, 0.5, 1, 1.5, 2, 3, 4, 6, 8,
      10 and 12 h after drug administration. The quantitation of sotalol enantiomers
      were performed by a stereoselective HPLC method with fluorescence detection
      previously published. A one open compartment model was applied and the main
      pharmacokinetic parameters obtained for R-/S-sotalol were, respectively (Mean +/-
      SD): CSSMAX = 1007 +/- 307/1040 +/- 340 ng/mL; TMAX = 1.82 +/- 0.6/1.83 +/- 0.6
      h; AUCSST = 6959 +/- 2153/7388 +/- 2563 ng.h/mL; CISSr/F = 2.7 +/- 1.2/2.5 +/-
      1.2 mL/min/kg and VdSS/F = 1.9 +/- 0.9/2.0 +/- 1.0 L/kg. The pharmacokinetic
      parameters of R,S-sotalol were within the published range and the kinetic
      parameters for the isomers were grouped as two independent samples and
      statistically compared. In conclusion, stereoselective pharmacokinetic for
      sotalol was not observed in cardiac arrhythmic patients, i.e., both R- and S
      sotalol enantiomers have the same pharmacokinetic profile.

PMID- 12064058
TI  - Kinetic spectrophotometric determination of ascorbic acid.
AB  - A simple, rapid kinetic spectrophotometric method was developed for the
      quantitative estimation of ascorbic acid. The method is based on in situ
      oxidation of quercetin with N-bromosuccinimide into a red colored compound which
      was measured at 515 nm. The rate of the reaction was followed by measuring the
      decrease in absorption intensity of oxidized quercetin as a result of its
      reduction by ascorbic acid. Ascorbic acid in the range of 2-25 micrograms/ml was
      determined using slope and fixed time methods. In addition, the variable time
      method allowed the determination of 5-25 micrograms/ml of ascorbic acid.
      Interference from frequently encountered excipients, additives, some amino acids
      and minerals was studied. The method was applied for determination of ascorbic
      acid in some pharmaceutical preparations with average recovery of 98.52% and RSD
      not exceed 3.52%.

PMID- 12064059
TI  - High-performance liquid chromatographic determination of alpha-amino acids in
      pharmaceutical dosage forms using aqueous mobile phase containing copper (II)
      ions.
AB  - A simple high-performance liquid chromatographic method was developed and
      validated for the determination of three alpha-amino acids (glycine, lysine,
      cysteine) and the amino acid derivative (N-acetylhomocysteine thiolactone) using
      aqueous mobile phase containing copper (II) ions. These amino acids were
      extracted from tablets, vials, effervescent salts and syrups and quantitatively
      diluted by the mobile phase. The separation was carried out on zorbax TMS column.
      The mobile phase was either 1.0 x 10(-3) M CuSO4 or 1.0 x 10(-3) M CuSO4 with
      1.0% trimethylamine, pH 4.0. A linear relationship was obtained between detector
      response at 232 nm and the concentration of the studied amino acids in the range
      of 1.5-50 ng/microL. The intraday precision for 10-replicate samples varied from
      0.59-2.66 while the interday precision ranged from 0.91-3.55 as CV%. A good
      recovery percentage was obtained in the analysis of many dosage forms ranging
      from 96.93 to 100.85 with a CV% from 0.33 to 1.74. The presented chromatographic
      separation method does not depend on any pretreatment or derivatization. The
      described chromatographic conditions, for both linearity and sensitivity, are
      sufficient for the selective determination of the cited amino acids. The
      interference from other combined pharmaceutical ingredients was resolved.

PMID- 12064060
TI  - Solubilization of a naphthoquinone derivative by hydroxypropyl-beta-cyclodextrin
      (HP-beta-CD) and polyvinylpyrrolidone (PVP-K30). The influence of PVP-K30 and pH
      on solubilizing effect of HP-beta-CD.
AB  - The effects of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and
      Polyvinylpyrrolidone (PVP-K30) on the solubility of 2-Hydroxyl-N-(3-methyl-5
      ethylisoxazolyl-4-yl)-1,4-naphthoquinone-4-imine (I) were investigated, this
      compound, a synthetic derivative of isoxazolylnaphthoquinones, has proved to
      exhibit important biological activity against the causative agent of Chagas'
      disease and against Staphylococcus aureus. In addition, the effect of co
      administration of a water-soluble polymer (PVP-K30) and ionization of I on the HP
      beta-CD solubilizing effect was also examined. HP-beta-CD and PVP-K30 possess a
      significant solubilizing effect by themselves. PVP-K30 increases the solubilizing
      effect of HP-beta-CD by enhancing the apparent stability constant (Kc) of the I:
      HP-beta-CD complex. The addition of 0.5% (w/v) PVP-K30 to the complexation medium
      results in a 83% increase in the stability constant of the complex. The HP-beta
      CD solubilization of I can also be improved by ionization of the drug molecule
      through pH adjustments. Although the Kc of the I complex is larger in the neutral
      form, a higher overall solubility is attained when I is in its ionized form. A 38
      fold solubility enhancement is possible by using a combined approach of pH
      adjustment and complexation with HP-beta-CD.

PMID- 12064061
TI  - Effect of bio-adhesive polymers, sodium salicylate, polyoxyethylene-9-lauryl
      ether and method of preparation on the relative hypoglycemia produced by insulin
      enteric coated capsules in diabetic beagle dogs.
AB  - The hypoglycemic effect of oral insulin capsules coated with pH-dependent
      Eudragit S100 and containing various absorption promoters was studied in
      hyperglycemic beagle dogs. The absorption enhancers used were bio-adhesive
      polymers, sodium salicylate and non-ionic surfactants. A comparative study of the
      bio-adhesive polymers, polycarbophil (PC), hydroxypropyl methylcellulose (HPMC)
      and carbopol 934 in insulin coated capsules, revealed no significant difference
      between the insulin capsules containing these polymers giving a relative
      hypoglycemia (RH) values ranged from 4.3 +/- 2.3% to 6.5 +/- 5.1%. It was also
      found that the method of preparation of the mixture of the bio-adhesive polymer
      with insulin either by physical mixing or freeze-drying did not affect the RH
      values obtained. Sodium salicylate, when used in insulin enteric coated capsules
      (50 mg) mixed with insulin as a physical mixture or prepared by wet granulation
      using 10% polyvinyl pyrollidone (PVP) or by freeze drying, produced RH values
      ranged from 7.3 +/- 2.9 to 9.4 +/- 3.7%. When sodium salicylate (100 mg) was used
      with insulin in freeze-dried granules an RH value of 10 +/- 2.6% was produced. As
      the dose of insulin increased from 6 to 9 U/kg, the AUC of the enteric coated
      capsules containing 50 mg sodium salicylate increased from 73.2 +/- 27.8 to 121.4
      +/- 102.7% reduction but the RH id not significantly change. Insulin capsules
      containing polyoxyethylene-9-lauryl ether (POELE) used in its optimum
      concentration (2%), found in these experiments, produced a RH of 9.5 +/- 6.8%
      when prepared as granules by wetting with few drops of absolute alcohol in
      presence of PC (50 mg). Insulin capsules containing lower (1%) or higher (3%)
      concentrations of POELE and prepared with PC, 50 mg by wet granulation produced
      lower RH of about 6%. The enteric coated oral insulin capsules containing insulin
      (6 or 9 U/kg) and sodium salicylate (50 mg) as an absorption promoter together
      with the bioadhesive polymer polycarbophil (50 mg) and prepared either by wet
      granulation using ethanol or by freeze drying are the best formulations to be
      used. They achieved a reduction in plasma glucose levels of about 25-30% and RH
      of about 10%. Also insulin (9 U/kg) capsules containing 2% POELE produced 28%
      reduction in plasma glucose levels and RH of 9.6 +/- 6.8%.

PMID- 12064062
TI  - Psychotropic drugs in Bulgaria-frequency and risk of adverse drug reactions.
AB  - The aim of the study is to determine the frequency and risk of appearance of
      adverse drug reactions/ADRs/during the treatment with psychotropic drugs. The
      first part of the study is an analysis of the use of the psychotropic drugs for
      one-year period of time in our country, performed by DDD methodology. An attempt
      is made to equalize the Bulgarian list of the psychotropic drugs with the ATC
      classification and to estimate the DDD/1000/day. The data for Bulgaria is
      compared with that of the other countries. The collected data for the
      psychotropic drug use is divided into 2 groups: Psycholeptics and
      Psychoanaleptics. It is made an attempt to explain the main differences between
      them. The number of the standard therapeutic courses/NT/is used for assessment of
      the frequency and risk of ADRs. The results from the study show that the
      determined frequency of appearance of ADR for the different drugs is within
      "rare" and "very rare' for 100,000 inhabitants, according to the WHO terminology.
      Only for the drug Tardyl (EGIS Pharmaceuticals, Hungary) with INN Aminobarbitalum
      + Glutethimidum + Promethazini hydrochloridum the frequency is above 1%. That
      fact makes us to recommend a limitation of the prescription and usage of this
      drug to the Bulgarian Ministry of Health and to the National Drug Agency.

PMID- 12064063
TI  - Synthesis and pharmacological activity of 1,4-benzodiazepine derivatives.
AB  - 2-Aminobenzamides (3a-g) were prepared starting with isatoic anhydride. These
      compounds reacted with chloroacetic acid to give (4a-g), which were cyclized by
      dicyclohexylcorbodiimide to afford (5a-g). The preliminary pharmacological
      screening revealed that some of the new 2H-1,4-benzodiazepin-3,5(1H,4H)-dione
      derivatives (5) exhibited CNS-depressant and anticonvulsant activities.

PMID- 12064064
TI  - Effect of the Lourdes water on "chlorinated water".
AB  - The present study demonstrated that the decay of chlorine concentration in
      samples of common water, additivated with free chlorine, is significantly slower
      if a certain amount of water taken from the Marian Sanctuary of Lourdes is added
      to the sample to be tested. The observed phenomenon is independent of the
      dilution ratio of the Lourdes water in spring water, that is, it practically
      identical both at low dilution (1:200) and at high dilutions (1:1 x 10(23)).

PMID- 12064065
TI  - 4(3H)-Quinazolinones. Antimicrobial 4(3H)-quinazolinones. Part III.
AB  - The authors present recent works published world-wide presenting 4(3H)
      quinazolinones of antimicrobial activities. Structures and syntheses of
      pharmacologically active compounds are described.

PMID- 12064066
TI  - [Etiopathogenic and clinical aspects of asymmetry].
AB  - Complex dysmorphies, asymmetries can affect the various elements of the
      stomatognathic system: cranial base, maxilla, mandible, musculature and dental
      arches, in the three dimensions of space. Their etiopathogenesis, as well as
      their clinical forms, vary considerably. Dysembryopathies, growth disorders, TMJ
      damages, postural or functional disorders and dental anomalies can create,
      according to their severity and their moment of appearance, severe or minor
      facial asymmetries, or asymmetries of the arches. An exo- and endobuccal clinical
      examination endeavors to specify the localization and the severity of the damage,
      and to evaluate the importance of the possible alveolar compensations.
      Consolidated by additional examinations, it enables the clinician to
      differentiate the various forms of asymmetries.

PMID- 12064067
TI  - [Three-dimensional imaging and cephalometry of cranio-facial asymmetry].
AB  - The 75th meeting of the French Orthodontics Society will be held in Biarritz May
      8-9-10-11 2002. The main topic for discussion will be: "facial asymmetry". During
      the meeting, authors will present study of facial asymmetries using a new
      innovative three-dimensional cephalometry. The method combines CT scans data,
      anatomical landmarks and mathematical tools to create, using the "Cepha"
      software, a 3D model of the human face. Balance and symmetry of the model are
      stable enough to define normality for each individual even with different ethnic
      and cultural origins. Unbalance and asymmetry characterize pathologies. Follow up
      shape and size of models allows growth prediction and modeling. The model is in
      the process of becoming the indispensable reference for all those who are
      interested in studying the human face: Orthodontics, Surgery, Anatomy,
      Anthropology, Plastic surgery, Forensic Medicine.

PMID- 12064068
TI  - [Occlusal aspects of asymmetry].
AB  - The dysfunctions of the masticatory apparatus can exhibit many different aspects,
      and multiple etiologies. If, among those, the occlusal causes are minimized today
      by a majority of the authors, it is nevertheless recognized that asymmetries
      represent a risk factor for the appearance and the development of dysfunctional
      pathologies for the masticatory apparatus. In presence of such dysmorphoses, it
      is of primary importance to proceed to dysfunction screening, which may be
      followed by a specialized clinical examination of the masticatory apparatus
      completed when required, by supplementary investigations. This stage enables both
      to pose the indispensable diagnosis, to evaluate the capacities for adaptation
      and suggest a coherent therapeutic approach, always starting with reversible
      treatments prolonged after re-evaluation and validation of their justification,
      by the stabilization of the occlusal relationships, a phase in which orthodontics
      often intervene.

PMID- 12064069
TI  - [Orthopedic approach to asymmetry].
AB  - Asymmetry being a clinical manifestation of various pathologies, the orthopedic
      attitude greatly varies from one practitioner to another. Thanks to a better
      knowledge of the etiopathogenesis, the orthopedic approach in some particular
      cases reveals very effective, either alone or together with other therapeutics.
      In mandibular laterodeviations most often consecutive to a maxillary contraction,
      the best treatment is to expand maxilla which will allow a mandibular centric
      repositioning. This therapy is often achieved early to limit the asymmetric
      expression of growth and normalize the dental eruption. In unilateral condylar
      hypoplasias of variable extension, from a simple defect in condylar growth to a
      hemifacial microsomia, the therapeutic attitude has mostly evolved. A surgical
      orthodontic protocol can integrate an increasingly significant orthopedic phase
      in the course of time. Some authors show that a surgical case may be treated
      originally only with the help of orthopedics. The devices used are of activator
      or hyperpropulsor type. In unilateral condylar hyperplasias, orthopedic therapy
      must be considered with reservations.

PMID- 12064070
TI  - [Orthodontic approach to asymmetry].
AB  - From an orthodontic point of view, asymmetries can be gathered in three great
      clinical entities: mandibular lateral deviations, dental asymmetries without
      skeletal involvement, skeletal asymmetries. Once the therapeutic aims and the
      principles of the orthodontic approach of these dysmorphoses have been recalled,
      the authors present the various orthodontic means implemented in this type of
      treatment. Four cases treated illustrate those types of treatment. Vertical non
      surgical asymmetry may have an obvious local origin, for instance, a unilateral
      damage to a nerve. but usually, there is no evident origin. Frequently the
      occlusal slippage of a severe sagittal or a vertical malformation, which may
      evolve as a borderline surgery case, is suspected to be the real cause. In these
      cases, the diagnosis is always late, with the ending growth. The treatment needs
      peculiar strong asymmetric mechanics and, sometimes, unilateral mixed
      extractions. The post-treatment occlusion can be unstable; for this reason, the
      finishing steps must be carefully conducted. Four clinical case reports develop
      these points ov view. Multidisciplinary treatments prove very useful to solve
      three types of clinical situations. In the adult patient, facial esthetics are
      indicated in severe dentofacial asymmetries. Esthetic improvements of dental
      nature are still required in deviated smiles, or frontal tippings of the occlusal
      plane. In addition, asymmetrical intermaxillary relationships will lead to
      functional anomalies: TMJ disorders, dental wear or lingual dysfunctions.
      Finally, multidisciplinary treatments in the adult concern the occlusal
      transverse anomalies, the lateral crossbites, the Class II subdivisions, the
      deviations of the inter-incisor midlines or unilateral edentulousness. The
      various plans of treatment, as well as the orthodontic mechanics used, are
      illustrated in the following development by clinical cases.

PMID- 12064071
TI  - [Surgery of asymmetry].
AB  - Endeavoring to present, within a few pages, an exhaustive work of all the
      surgical proposals, regarding the multitude of ethiopathogeneses, is quite
      utopic. The author considers the evaluation of the asymmetrical patient and
      underlines in the complementary examinations the advantage of 3D
      tomodensitometry. A chapter is devoted to presurgical orthodontic preparation
      aimed at counteracting the compensations, which affect the maxillary and
      mandibular alveolar support. The therapeutic strategy calls upon "combined"
      programs. A "range" of osteotomies is suggested within the framework of the most
      frequent dysmorphoses. Two more complex pathologies, which may be met by the
      orthodontist, are evoked: condylar hyperplasia and temporomandibular ankylosis
      related to inflammatory affections and traumatisms. Glossoplasty is the rule in
      some hemihypertrophies. Relapses, hindering the stability of the result, can be
      thwarted by overcorrections, different means of splinting and postoperative
      kinesitherapy. Iconography and clinical observations illustrate both the
      orthodontist's and the surgeon's approach: they heighten the reader's awareness
      of the various problems linked with asymmetry.

PMID- 12064072
TI  - Atopic ocular disease.
AB  - Atopic ocular diseases involve a spectrum of immuno-inflammatory responses. There
      are minimal pathologic changes with SAC. With PAC, there is increased mast cell
      activation and late-phase inflammatory cell infiltrate as a consequence of
      continued allergic stimulation. Associated with the more chronic and severe forms
      of atopic ocular disorders, GPC, VKC and AKC, there is persistent mast cell,
      eosinophil, and lymphocyte activation resulting in pathologic changes.
      Therapeutic intervention for atopic ocular diseases has focused on symptomatic
      improvement. However, with an increasing understanding of the molecular
      mechanisms associated with the allergic inflammatory response, experimental
      studies may facilitate the development of preventative strategies.

PMID- 12064073
TI  - Mechanisms of acquired blepharoptosis.
AB  - Blepharoptosis can be the presenting symptom in a variety of disorders ranging
      from the relatively common and benign levator dehiscence to debilitating and
      potentially life-threatening conditions such as myasthenia gravis and aneurysms
      of the posterior communicating artery. For these reasons, a comprehensive
      understanding of the clinical and pathophysiological features of the different
      causes of acquired ptosis is essential in guiding the ophthalmologist toward the
      appropriate medical and surgical management of these patients (see the following
      list).

PMID- 12064074
TI  - The pathophysiology of thyroid-associated ophthalmopathy.
AB  - TAO is an inflammatory disease of the orbital tissues. The effects of
      inflammation, mediated through cytokine release, include proliferation of
      fibroblasts, increased deposition of extracellular matrix, and adipocyte
      differentiation and proliferation. As a result, edema, enlargement of the
      extraocular muscles, and increased volume of the orbital soft tissues occur with
      ensuing exophthalmos and, in some patients, compression of the optic nerve.
      Edema, inflammation, and late fibrosis, account for the decreased function of the
      extraocular muscles, despite relative preservation of the fibers themselves. The
      recruitment of T cells to the orbits of these patients may result from the
      expression of the target of the aberrant immune response in Graves' disease, the
      TSH receptor, in the orbits of patients with TAO. The orbital fibroblasts,
      especially those present within patients with TAO, may be more sensitive to the
      effects of cytokines, accounting for the frequent, and relatively selective,
      involvement of the orbit in Graves' disease. Insight into the cellular and
      molecular pathways proposed in this cascade introduces potential sites for new
      therapeutic approaches and understanding of the mechanisms of current treatments.
      Corticosteroids, used frequently in the treatment of TAO, have a detectable
      effect at the molecular level. While glucocorticoids do not directly influence
      extracellular matrix production [62] or baseline proliferation of orbital
      fibroblasts [27] they do attenuate the effect of several cytokines on inducing
      proliferation of these fibroblasts or extracellular matrix production, and this
      influence is greater in fibroblasts from TAO patients [27,36]. The consistent
      observation of early inflammation suggests that immunomodulation early in the
      course of the disease should be a primary goal of management of TAO. The
      elucidation of the specific cytokines that are released and active in the orbits
      of patients with TAO may aid in the development of more specific immunomodulatory
      therapies. Improved understanding of the pathophysiology of TAO may also help
      identify more rational approaches to treatment. For example, identification of
      the molecules involved in the inflammatory cascade which results in TAO may help
      predict progression of disease and identify specific treatment modalities which
      may benefit individual patients [11,70].

PMID- 12064075
TI  - Idiopathic orbital inflammation: ocular mechanisms and clinicopathology.
AB  - Pathogenesis of idiopathic orbital inflammation remains elusive but several lines
      of evidence point to immune-mediated processes as the likely underlying ocular
      mechanism. The exact nature of the immunological process and possible role of
      infection need to be elucidated in greater depth. There is an obvious need for a
      more satisfactory animal model for orbital pseudotumor. Given the prevalence of
      recurrent and persistent orbital inflammation, therapeutic alternatives to
      corticosteroids need to be further explored and systematically investigated.

PMID- 12064076
TI  - Myopia and models and mechanisms of refractive error control.
AB  - Myopia represents a failure of the normal process of emmetropization, which is
      essentially endogenous to the eye. Emmetropization involves defocus detection at
      the level of the amacrine and bipolar cells of the outer retina, diffusion of a
      signal or signals across the retinal pigment epithelium and choroid, and
      alteration of the scleral matrix, likely through modulation of proteoglycan
      synthesis. Elucidating and effectively bolstering the deficient steps in this
      regulatory pathway would mark a significant advance given myopia's tremendous
      impact. Clinical experience, longitudinal studies, epidemiological data and
      numerous animal experiments have enhanced our understanding of myopia.
      Interpretation of the epidemiological data is often complicated by the
      difficulties of distinguishing environmental from genetic influences, especially
      those pertaining to slow developmental changes. Likewise, it is important that
      the animal models be interpreted with an appreciation that the human eye varies
      structurally and developmentally from that of other species. Studies of the chick
      eye have formed the basis for several hypotheses of myopic development, but the
      chick does not possess a fovea or retinal blood supply. It is unclear whether
      these differences alter the pathways of emmetropization. Even closely related
      primate species can exhibit different responses to form deprivation conditions,
      suggesting differing mechanisms of eye growth control. Monocular occlusion of the
      rhesus macaque, for instance, results in myopia when the ciliary muscle is
      paralyzed or the optic nerve cut, but does not in the stumptailed macaque,
      suggesting a role of excessive accommodation in the development of myopia in the
      stumptail but not the rhesus [36]. Given such variability in the models a
      persisting element of continued myopia research must be an evaluation of the
      relevance of any given model to the human condition. In this regard, the study of
      changing patterns of gene expression within and among species during
      emmetropization and myopic progression may offer a productive avenue for future
      research.

PMID- 12064077
TI  - Mechanisms of disease: Fuchs' endothelial dystrophy.
AB  - Fuchs' endothelial dystrophy is a common disease that has been widely studied
      since its initial report in 1910 by Ernst Fuchs. Although its clinical course and
      pathologic characteristics are well described, the etiology and inheritance
      pattern are still ambiguous. Ongoing work is evaluating the role of mitochondrial
      DNA in the pathogenesis of FED. Significant advances in the surgical treatment of
      FED, in part utilizing some of the techniques of refractive surgery, are
      promising thus far. Larger case series are needed to fully assess the safety,
      efficacy and indications of these techniques. Indeed, the time is right to take
      "a fresh look at an aging disease" [9].

PMID- 12064078
TI  - Mechanisms of corneal ulceration.
AB  - Corneal ulceration is a significant cause of visual morbidity. Although this
      discussion has primarily focused on the local factors involved in non-immune
      related sterile corneal ulcerations, an understanding of these mechanisms is
      important since a final common pathway that is conceivably relevant to all forms
      of corneal ulceration exists. With respect to the treatment of chronic sterile
      ulcerations, our contemporary armamentarium is extensive; an acknowledgement to
      the inadequacies of any single strategy. A sound appreciation of the subtleties
      involved in the pathogenesis of corneal ulceration and the orchestration of wound
      repair will lead us towards more effective strategies to decrease inflammation
      associated with ulceration, promote corneal wound healing, and ultimately provide
      better care for our patients.

PMID- 12064080
TI  - Epithelial and fibrous downgrowth: mechanisms of disease.
AB  - Epithelial downgrowth is a rare, but potentially devastating, complication of
      intraocular surgery and trauma. It has been suggested that the incidence is
      declining with modern surgical techniques, but further long-term analysis is
      needed to determine whether this in fact is true. While clinical observations and
      experimental studies have helped to elucidate factors involved in the development
      of this disease, a precise understanding of its pathogenesis is unknown. Given
      the difficult management and poor prognosis of this disease, further study and
      heightened clinical awareness are needed to better understand this disease
      process.

PMID- 12064079
TI  - Lamellar keratitis following laser-assisted in situ keratomileusis.
AB  - Distinguishing between an infectious or sterile lamellar keratitis is the most
      important first step in evaluating patients with interface infiltrates after
      LASIK. The mechanisms by which infectious keratitis develops are more
      straightforward than for DLK and deal with the introduction of microbial
      pathogens into the lamellar flap during LASIK. Prevention emphasizes reducing
      contamination risks and treating any pre-existing ocular infections. The
      mechanisms of the development of DLK are likely multifactorial, and factors such
      as microkeratome debris, eyelid secretions, other debris, epithelial defects, and
      bacterial endotoxin have been suggested. Overall, much remains to be elucidated
      in order to devise effective prevention measures.

PMID- 12064081
TI  - Mechanisms of disease: cataracts.
AB  - Studying the mechanisms that are responsible for the transparency of the lens we
      see that multiple factors are involved in the maintenance of lens clarity as well
      as in cataractogenesis. Is there a unifying mechanism? Since the function of the
      lens is the transmission of electromagnetic radiation in the visible spectrum,
      fundamental physical laws should apply. Attenuation of a light beam that passes
      through a medium happens by two major processes: absorption and scattering. In
      absorption, light energy is dissipated into heat as the result of energy
      absorbing electronic transitions. In scattering, radiation is redirected away
      from the incident pathway, thereby reducing the transmitting power. Depending on
      the angular dependence of the scattered light, the wave front of the transmitted
      light is distorted. In the case of cataract, the primary factor is turbidity
      secondary to scattering. A perfectly uniform medium exhibits no light scattering;
      thus a continuous medium can scatter light only when it contains spatial
      fluctuations around the mean density governed by specific equations. These
      equations simply state that the amplitude of scattering is proportional to the
      Fourier amplitude of the density fluctuations in the medium [12]. Electron
      micrograph analysis using Fourier transformation has shows an increase in the
      fluctuation of spatial density of the opaque fiber [12,26,37,93]. Thus, all
      transparency mechanisms and all cataractogenic factors can be thought of as
      opposing effectors of spatial density fluctuation affecting scatter and
      antithetical producers of light absorbing moieties.

PMID- 12064082
TI  - Glaucomatous optic neuropathy: mechanisms of disease.
AB  - The optic neuropathy of glaucoma appears to be multifactorial in etiology. Both
      mechanical and vasogenic theories remain viable explanations for the observed
      nerve damage and the destructive effect of trophic withdrawal could be espoused
      by either theory. Each theory feeds into the final common pathway of cell death;
      even the immune system may kill cells in glaucoma by apoptosis. This knowledge
      has led to the hope that glaucomatous nerve damage can be curtailed or even
      prevented with the use of neuroprotective agents. Indeed, there are many
      intriguing new therapeutic possibilities on the horizon. Until evidence from
      clinical trials demonstrates the effectiveness of these agents however, control
      of IOP will remain the mainstay of treatment for glaucoma.

PMID- 12064083
TI  - Vascular endothelial growth factor gene regulation and action in diabetic
      retinopathy.
AB  - It is conceivable that VEGF inhibition may prevent edema formation at the early
      stages of diabetic retinopathy. Once the retina is irreversibly ischemic or new
      vessels have formed, however, antagonizing VEGF may lead to retinal necrosis due
      to chronic ischemia. An alternative approach would be the induction of
      neovascular maturation. Once the new vessels become mature, retina ischemia
      resolves. There would be no edema, hemorrhage, or retinal detachment. Acute
      administration of an angiogenic molecule called angiopoietin-1 protects
      vasculature from leaking [103]. Angiopoietins bind to the endothelial cell
      specific receptor Tie 2 and play an important role is vascular development,
      especially vessel maturation. The proposed mechanisms include recruiting
      pericytes and organizing vascular matrix [103]. Since VEGF is constitutively
      expressed at low levels in normal eyes [46], it may contribute to the maintenance
      of vascular integrity. Thus, oversuppression of VEGF expression may be harmful to
      the retinal vasculature. Inhibiting VEGF action may need to be delivered in a
      tightly regulated manner such that complete inhibition may be avoided both to
      maintain basal levels and to provide rapid reversal of inhibition when acute
      angiogenic responses are desired [72]. VEGF is involved in normal angiogenic
      processes in adults such as cardiac collateral circulation, wound healing and
      menstrual cycle [27]. Local drug delivery seems to be more appealing than
      systemic administration to avoid the side effects. Some VEGF antagonists, such as
      VEGF receptor chimeric protein and the VEGF neutralizing antibodies are large
      molecules with poor diffusion into tissues. Repetitive invasive procedures such
      as intravitreal injection seem to be impractical due to potential complications
      of retinal detachment and bacterial infection. Recent progress on transscleral
      delivery of bioactive proteins and DNAs to the choroid and retina provides
      promising future on local delivery of therapeutic agents [12,13].

PMID- 12064084
TI  - Varicella-zoster virus: mechanisms of pathogenicity and corneal disease.
AB  - As ophthalmologists, many of our patients suffer from the ravages, both ocular
      and non-ocular, of the varicella-zoster virus. This article is a comprehensive
      review of the pathogenetic mechanisms of this ubiquitous virus. We review the
      basic virology, mechanisms of varicella, zoster, latency, reactivation, and the
      host immune response to the virus. Herpes zoster ophthalmicus is discussed with
      special attention to the cornea and mechanisms of viral keratitis.

PMID- 12064085
TI  - Mechanisms in proliferative vitreoretinopathy.
AB  - The wound-healing paradigm for proliferative vitreoretinopathy has provided
      numerous avenues for investigation into the pathobiology of the process. The
      emerging picture is a complex interaction of cytokines, matrix proteins, and
      metalloproteinases influencing cell behavior and resulting in the formation of
      undesirable periretinal membranes. It seems unlikely that focusing therapy on one
      particular target will be sufficient to stop the entire cascade of cellular
      events leading to proliferative vitreoretinopathy. Rather, multiple adjunctive
      agents targeted at different stages of the process and given at the appropriate
      time might be more successful in achieving improved visual outcomes for patients.

PMID- 12064086
TI  - Mechanisms of age-related macular degeneration.
AB  - AMD is a poorly understood disease at this time. Since it is the leading cause of
      blindness in the elderly in the developed world, there is a pressing need for
      better treatment. Therefore, there is extensive ongoing research in both
      pathogenesis and therapy of AMD. Epidemiological studies have shown significant
      risk associated with increasing age and cigarette smoking, future studies may
      identify environmental risk factors though at present studies have been
      inconclusive. Genetic studies may identify subgroups of disease and thus help
      provide a selective approach to treatment. The vascular model of AMD may provide
      better understanding of the blood flow and post capillary resistance and help in
      early and newer intervention in the disease. Vascular endothelial growth factor
      has been extensively studied in choroidal neovascularization. It has been
      demonstrated in human and animal models of CNV and VEGF antagonists are currently
      in clinical trial. Extensive work is ongoing to prevent and treat CNV with
      antiangiogenic agents.

PMID- 12064087
TI  - Understanding the etiology of Stargardt's disease.
AB  - Stargardt's disease is a form of juvenille macular degeneration. Patients with
      Stargardt's disease typically present in the first or second decade of life,
      complaining of decreased visual acuity. Recent research allows for a three-step
      explanation of the pathophysiology of Stargardt's disease: 1) Defective Rim
      Protein, a protein encoded by the ABCA4 gene, causes an accumulation of
      protonated N-retinylidene-PE in the rod outer segments; 2) A2-E, a byproduct of N
      retinylidene-PE, then accumulates in the RPE cells and is toxic to them; 3)
      Photoreceptors eventually die secondary to loss of the RPE support function. With
      our new knowledge of the etiology of Stargardt's disease, we can devise future
      studies directed at treating affected patients.

PMID- 12064088
TI  - Mechanisms of ocular disease.

PMID- 12064089
TI  - Sympathetic neural control of skeletal muscle blood flow and oxygenation.

PMID- 12064090
TI  - Antisense studies of brain GABAA receptors.
AB  - gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in
      the brain. The GABAA receptor complex, which is assumed to have a pentamer
      structure assembled from different polypeptide subunits, contains the binding
      sites for several clinically important compounds, e.g., the benzodiazepines and
      the barbiturates. A dysfunction of GABAergic inhibitory neurotransmission
      mediated via the GABAA receptor has been hypothesised to be a central factor in
      the pathogenesis of epilepsy. Antisense technology is based on the possibility of
      selectively inhibiting gene expression at the level of messengerRNA (mRNA). An
      antisense oligodeoxy nucleotide (ODN), a short synthetic single-stranded DNA
      molecule, is believed to inhibit the biosynthesis of a particular protein via
      nucleotide specific hybridisation to the mRNA encoding the protein. Antisense
      ODNs are used as tools for the investigation of the physiological roles played by
      individual proteins. The aim of the present study was to investigate the
      feasibility of selectively inhibiting the expression of a major subunit of the
      GABAA receptor complex in the rat brain in vivo by means of antisense technology.
      The thesis describes the changes observed following intrahippocampal
      administration of antisense ODN targeted to the GABAA receptor gamma 2 subunit.
      This subunit is a constituent of the majority of GABAA receptor complexes in the
      brain. Biochemical, morphological, electroencephalographic and behavioural
      changes induced by the antisense ODN treatment are described. The results support
      the notion that the primary event induced by the antisense ODN is a specific down
      regulation of the gamma 2 subunit protein and that this leads to a decrease in
      the number of functional GABAA receptors and a state of diminished hippocampal
      GABAergic inhibitory neurotransmission. Antisense ODN-treated rats spontaneously
      develop limbic status epilepticus; prolonged antisense ODN treatment results in
      severe neurodegenerative changes in the hippocampus. The results of the study
      support the hypothesis that the GABAA receptor is critically involved in
      epileptogenesis. The results are viewed as a contribution to the understanding of
      the GABAA receptor complex and of mechanisms of epileptic phenomena and neuronal
      cell death. The presented animal model is suggested as a pathophysiologically
      relevant model of temporal lobe epilepsy and limbic status epilepticus. The
      results may also be of value for the general characterisation of antisense
      technology as a neuroscientific tool.

PMID- 12064091
TI  - Epidemiology of emphysema in subjects with severe alpha 1-antitrypsin deficiency.

PMID- 12064092
TI  - Evidence of torture in the mid west region of Nepal.
AB  - INTRODUCTION: The aim of this study was to find evidence of torture in the Mid
      West Region of Nepal. METHODOLOGY: Interview and clinical examination of self
      reported torture-survivors in the Mid West Region of Nepal in the area of
      Nepalganj, which is on of the most important city in that region. Thirty-four
      persons (group A) were examined according to a programme performed by Physicians
      for Human Rights, Denmark. Furthermore, twenty-nine persons (group B) were
      interviewed according to an abbreviated programme performed by a local group of
      doctors. RESULTS: Testimonies of exposure to physical and psychological violence
      were validated, assessing the consistency between the reported exposure, reported
      ensuing symptoms and the results of clinical examinations. CONCLUSION: Torture
      has probably existed in Nepal for decades. The main reason given for torture is
      suspicion of political activity. Most of the torture takes place in District
      Police Offices, by the police. Episodes of torture performed by the Communist
      Party of Nepal, known widely as "the Maoists", have been reported. This
      investigation substantiates that torture is severely traumatizing for the
      survivor.

PMID- 12064093
TI  - Alloreactivity and the predictive value of anti-recipient specific interleukin 2
      producing helper T lymphocyte precursor frequencies for alloreactivity after bone
      marrow transplantation.
AB  - Allogeneic bone marrow transplantation (BMT) is a treatment modality with the
      potential of curing otherwise lethal diseases. The predominant indications for
      BMT are haematological malignancies. In BMT alloreactivity plays a pivotal role
      for the outcome. Graft-versus-host disease (GvHD) and graft-versus-leukaemia
      (GvL) are correlated manifestations of alloreactivity. Severe GvHD is one of the
      main causes of morbidity and mortality post-BMT. In the absence of GvL the risk
      of relapse is high. The main effector cells are T lymphocytes. Donor leukocyte
      infusion (DLI) for treatment of leukaemic relapse after BMT can induce durable
      remissions. DLI causes GvHD in the majority of the responding patients. However,
      a GvL effect may be present without evidence of GvHD and vise versa. The
      importance of alloreactivity for the treatment outcome prompted the interest for
      a predictive test of alloreactivity. Interleukin 2 (IL-2) producing helper T
      lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis
      (LDA) in the graft-versus-host direction were explored. The HTLp assay was
      optimized and the sources of error minimized to ensure sensitive and reproducible
      results. The IL-2 dependent cell line, CTLL-2 was optimized to detect 0.6 pg IL
      2. UV-B irradiation of the cells was demonstrated to effectively terminate
      proliferation of the responder cells and thus allow IL-2 to be detected in the
      whole culture volume. The design of the assay was explored by Monte Carlo
      simulations resulting in a design yielding frequencies with a coefficient of
      variation of 20% in the range of 1:20,000-1:1,000,000. The influence of
      autoreactivity of the donor and recipient cells was minimized as well as the risk
      of the stimulator cells producing IL-2. The HTLp frequencies correlated with the
      degree of human leukocyte antigen (HLA) disparity and the assays were able to
      detect minor histocompatibility antigen mismatches. The HTLp frequencies of 28
      HLA-identical sibling BMT pairs and 20 HLA-matched unrelated and partially HLA
      matched related BMT pairs were determined. HTLp frequencies from the HLA
      identical sibling BMT pairs had a median of 1:557,362 (range 1:9.511 to <
      1:2,500,000). The HTLp frequencies from the HLA-matched unrelated and partially
      HLA-matched related BMT pairs had a median of 1:88,110 (range 1:4.139-1:736,123).
      Analysis of the HLA-identical sibling BMT pairs in a high and a low HTLp
      frequency group above and below 1:500,000 showed a trend towards a higher risk of
      acute GvHD > or = grade II and a significantly higher risk of chronic GvHD in the
      high HTLp frequency group. This group had a significantly lower risk of relapse
      as well as a significantly better overall survival and leukaemia free survival.
      The HLA-matched unrelated and partially HLA-matched related BMT pairs were split
      evenly in a high and a low HTLp frequency group above and below 1:90,000. There
      was a significantly higher risk of acute GvHD > or = grade II and a trend towards
      a higher treatment related mortality (TRM) in the high HTLp frequency group.
      There were no differences in chronic GvHD, risk of relapse, overall survival and
      leukaemia free survival. Analyzing all 48 patients the risk of acute GvHD > or =
      grade II and TRM was significantly higher with HTLp frequencies > 1:100,000 and
      there was a trend towards a higher risk of relapse with low HTLp frequencies <
      1:400,000. Patients in the intermediate HTLp frequency group 1:100,000-1:400,000
      had a trend towards improved survival. The HTLp frequency seems to detect
      clinically significant differences in alloreactivity, that can be useful in donor
      selection, graft-engineering, T cell add-back and the pharmacological
      immunosuppression used after BMT.

PMID- 12064094
TI  - The role of allografts in revision arthroplasty of the hip.
AB  - The role of allograft tissue, including bone, cartilage and soft tissue, has
      become more defined in lower extremity reconstructive surgery. Revision
      arthroplasty of the hip commonly requires restoration of bone stock using
      allograft bone. Morcellized bone is used for contained defects on both the
      acetabular and femoral sides. Structural allograft bone is used for uncontained
      or segmental defects, and the results are less predictable; therefore, its use is
      more controversial. Alternatives include the jumbo cup, oblong cup, and high hip
      center on the pelvic side and tumor prostheses or distal fixation on the femoral
      side. These alternatives do not, however, restore bone stock, thus making further
      surgery more difficult. Structural grafts allow attachment of bone and soft
      tissue and restoration of the correct anatomy and have been shown to restore bone
      stock for further surgery, particularly on the acetabular side. Improvements in
      the quality and safety of banked bone and the development of surgical techniques
      have enhanced the results of structural allograft bone grafting. Restoring bone
      stock in revision arthroplasty of the hip is an accepted standard for the patient
      likely to undergo further surgery. Continuing to develop technologies that will
      facilitate the use of allograft tissue is imperative.

PMID- 12064095
TI  - Humeral head replacement: techniques and soft-tissue preparation.

PMID- 12064096
TI  - Principles of joint arthroplasty as applied to the ankle.
AB  - The challenges for the development of a successful total ankle prosthesis are
      formidable. The forces at the ankle are large and the surface area for bone
      support is [figure: see text] small. The size and shape of the talus make
      expansion of the surface area for fixation very difficult and greatly minimize
      options for prosthetic revision. The quality of bone in the distal tibia
      frequently may be questionable, and the bone strength is not uniform across the
      distal tibia. Finally, the soft-tissue envelope at the ankle is poor. The distal
      location of the ankle magnifies the circulatory risk in any patient with
      peripheral vascular disease. Wound problems are more common and more dangerous
      than in more proximal sites. Fractures and other injuries are very common at the
      ankle and potentially can add to the frequency of complications. The proximity of
      the medial and anterior neurovascular structures also increases the likelihood of
      serious complication. Total ankle arthroplasty is much closer to the limit of
      what can be successfully accomplished with acceptable risk to the patient. There
      is little room for error. This, coupled with the larger compressive forces
      generated at the ankle, makes successful ankle arthroplasty a bigger challenge
      than arthroplasty at the hip or knee.

PMID- 12064097
TI  - The Agility total ankle replacement.
AB  - The Agility Total Ankle System can be used in most arthritic conditions that
      involve the ankle joint, including many angular deformities that result from
      trauma or degenerative wear. The surgeon must be prepared to realign the ankle
      and to achieve soft-tissue balancing at the time of the surgery to avoid late
      failures. Proper patient selection is very important, and certain conditions,
      including diabetes with peripheral neuropathy, poor skin quality or poor
      circulation, and deficient bone stock, must be avoided to achieve a successful
      outcome. The surgical procedure must be done in a precise manner, with selection
      of the proper size of prosthesis and accurate insertion of the components in all
      directions. Proper tensioning of the joint is also paramount to achieve long-term
      stability. The precise degree of tensioning is still somewhat controversial,
      although with experience the deltoid end point can be readily determined in most
      patients. The follow-up care of these patients is very important, not only from
      the standpoint of compliance but also because any long-term problems must be
      recognized and treated before the implant is lost.

PMID- 12064098
TI  - The Scandinavian total ankle replacement prosthesis.

PMID- 12064099
TI  - Eighteen-year evaluation of cementless meniscal bearing total ankle replacements.

PMID- 12064100
TI  - Salvage of failed and infected total ankle replacements with fusion.

PMID- 12064101
TI  - Principles of management of the severely traumatized foot and ankle.

PMID- 12064102
TI  - The diabetic foot: basic mechanisms of disease.
AB  - There remains vast truth in the statement "neuropathy causes diabetic foot
      pathology." However, if it were really that straightforward and if our
      understanding were complete, it is doubtful that ulceration and neuroarthropathy
      would be the public health problems that they are today. Diabetes is an insidious
      disease, and almost every component of the spectrum of hyperglycemic
      complications is active in creating foot lesions. These include dramatic
      alterations in all components of the peripheral nerves, the mechanical
      characteristics of bones and soft tissues, gait kinematics, the vasculature at
      both a microscopic and a macroscopic level, the immune system, and the
      fundamental processes of wound healing. Clinical treatments that address the
      biologic aspects of the problem without considering the mechanics, or vice versa,
      can sometimes be effective but fail to take advantage of all of the potential
      means to succeed. The greatest potential for future clinical advance lies in
      understanding and simultaneously addressing the many synergistic factors that
      cause both ulceration and neuroarthropathy.

PMID- 12064104
TI  - Complications following distal radial fractures.

PMID- 12064103
TI  - Surgical treatment of common displaced and unstable fractures of the hand.

PMID- 12064105
TI  - Glenoid resurfacing in shoulder arthroplasty.

PMID- 12064106
TI  - Indications for lumbar microdiskectomy.
AB  - A very high percentage of patients coming to surgery for large disk extrusions
      and sciatica do very well with minimally invasive diskectomy. In most patients
      given relatively early surgical treatment, the primary predictor of outcome is
      the size of the disk herniation and the remaining competency of the anulus
      fibrosus. With the passage of time and with prolonged disability before surgery,
      psychosocial factors become increasingly important in determining outcomes.
      Factors such as psychological distress, depression, involvement with workers'
      compensation claims and disability claims, drug and alcohol abuse, and level of
      education appear to be secondary factors, at least initially, in subjects with
      large extruded fragments. In subjects with smaller disk herniation or in those
      with chronic disability, these factors may indicate a higher risk of treatment
      failure.

PMID- 12064107
TI  - Lumbar microdiskectomy: microsurgical technique for treatment of lumbar herniated
      nucleus pulposus.

PMID- 12064108
TI  - Microsurgery in the lumbar intertransverse interval.
AB  - The intertransverse interval has long been known as a place to lay bone graft in
      hope of achieving a solid arthrodesis. Opening it to use the interval to gain
      access into the foraminal and extraforaminal regions of the spinal canal has only
      recently been done. The anatomy is simple and embodies a common lumbar spine
      principle, which is to find a pedicle, because medial to it will be a nerve root.
      In the intertransverse interval, the lateral border of the pars interarticularis
      is on the same sagittal plane as the medial border of the pedicle (except for
      L5). Once through the interlaminar window, the anatomy is very simple--there is
      only one nerve root to find. The limited ability to manipulate instruments and
      the increased depth of the exposure make the use of the operating microscope very
      important. More so than axial MRI cuts and far more so than axial CT cuts,
      parasagittal MRI cuts reveal a true picture of the openness of the foramen. The
      type of pathology, whether E/FLDH or foraminal stenosis, can be clearly
      delineated on parasagittal MRI. It is important, however, that radiologists not
      overcall foraminal stenosis on axial cuts, either CT or MRI. Foraminal stenosis
      is easily decompressed by a lateral approach and is very difficult to completely
      decompress from within the spinal canal. If foraminal stenosis has been left
      behind from a previous midline SCS decompression, and if the patient has
      continuing leg pain, then it is easy to avoid the previous midline surgical route
      and take a paraspinal muscle-splitting approach to complete the foraminal
      decompression. Other, as yet undiscovered uses for the intertransverse window
      approach likely exist. The senior author has used this approach to remove a third
      or fourth-time recurrent canalicular disk herniation where the fragment is
      opposite the disk space (the usual situation). By avoiding the previous scarred
      in canal and nerve root, it has been possible to remove the ruptured disk.
      Visualization, however, is not good with this approach.

PMID- 12064109
TI  - Advantages of the operating microscope in lumbar spine surgery.

PMID- 12064110
TI  - Microsurgical techniques in lumbar spinal stenosis.
AB  - The rationale for microsurgical decompression is to maximize neural decompression
      while minimizing the destabilization and resection of uninvolved structures.
      Microsurgical decompression is appropriate for most degenerative lumbar spinal
      stenosis because the pathoanatomy tends to be concentrated at the levels of the
      disk space and foramen. Careful preoperative analysis of the imaging studies will
      guide the surgeon to the most appropriate method of decompression for a
      particular patient and help focus the decompression to the appropriate regions.
      Thorough knowledge of surgical spinal anatomy is mandatory because the exposure
      is limited with a microsurgical approach; however, visualization can be excellent
      with proper attention to surgical technique.

PMID- 12064111
TI  - Diaphyseal humeral fractures: treatment options.
AB  - All of the current modalities have a place in the treatment of diaphyseal humeral
      fractures. Functional bracing renders a high rate of union and seems to be a safe
      method of treatment for most closed fractures. Type II and III open fractures
      seem to respond best to plate fixation or external fixation, particularly when
      there are associated neural or vascular pathologic findings. Patients with
      polytrauma who are unable to walk are also best treated with plate fixation.
      Plate fixation is also the best method of treatment when adequate alignment
      cannot be obtained with nonsurgical methods. Intramedullary nailing remains
      controversial because its complication rate is higher than that associated with
      either plate fixation or functional bracing. None of the treatments described is
      a panacea, and complications may occur with each one of them. An appropriate
      appreciation of the biologic response to the three modalities; an understanding
      of the indications, contraindications, and possible complications of the
      treatments; and a mastery of the techniques of application are essential for the
      attainment of satisfactory clinical results.

PMID- 12064113
TI  - Intramedullary nailing of forearm fractures.

PMID- 12064112
TI  - Intramedullary nailing of humeral shaft fractures.
AB  - The development of interlocking humeral nail systems has greatly broadened the
      indications for nailing of humeral shaft fracture. Rotational control is better
      than with earlier nail systems, and most nails have an oblong distal hole that
      allows axial loading of the fracture site with muscle contraction. When nailing
      is done with closed technique, loss of the fracture hematoma and periosteal
      stripping are avoided. Even when open reduction is required, periosteal stripping
      can be kept to a minimum. Surgical wounds are smaller, even when open reduction
      is necessary, and when closed nailing is done, bone grafting is unnecessary.
      Intramedullary nails are ideal for segmental fractures, pathologic fractures, and
      fractures in osteopenic bone. Because the arm usually is not a weight-bearing
      extremity, hardware failure is rare and union rates are equivalent to those of
      compression plate and screw fixation. Compression plates and external fixation
      certainly have their place for some fracture patterns and for severe wounds that
      are unsuitable for intramedullary nailing. The surgeon should be well versed in
      all three techniques and should be able to rapidly choose among these, depending
      upon the fracture pattern, skin wound, associated injuries, and overall condition
      of the patient.

PMID- 12064114
TI  - Complications of shoulder arthroplasty: infections, instability, and loosening.

PMID- 12064115
TI  - Controversies in intramedullary nailing of femoral shaft fractures.

PMID- 12064116
TI  - Glenohumeral arthroplasty: indications and preoperative considerations.
AB  - The indications for glenohumeral arthroplasty are severe pain and restricted
      range of motion associated with radiographic evidence of advanced glenohumeral
      arthritis. Nonsurgical management consisting of rest, physical therapy, and
      antiinflammatory medication should be tried before considering surgical
      management. It is important that each patient be evaluated on the basis of the
      clinical disease and radiographic characteristics of the underlying diagnosis.
      Preoperative considerations should include a careful assessment of bone quality
      and quantity and associated deformity. Evaluation of the soft tissues,
      particularly the rotator cuff and deltoid muscles, is essential because the
      success of total shoulder arthroplasty depends greatly on the integrity of these
      structures. Associated upper and lower extremity degenerative arthritis should be
      evaluated and carefully considered, particularly with respect to the timing of
      surgical management. Careful consideration of these factors is invaluable in
      obtaining successful outcomes of total shoulder arthroplasty.

PMID- 12064117
TI  - Risk factors associated with noncontact anterior cruciate ligament injuries in
      female athletes.
AB  - The cause of ACL injury in female athletes is multifactorial, with both intrinsic
      and extrinsic factors contributing. Health care professionals need to educate
      female athletes, their coaches, and their parents about the two most important
      factors, neuromuscular and biomechanical, that cause injury, in addition to
      strategies and exercises that may prevent injuries.

PMID- 12064118
TI  - Anterior cruciate ligament injuries in female athletes: prevention strategies.

PMID- 12064119
TI  - Lower extremity motor control-related and other risk factors for noncontact
      anterior cruciate ligament injuries.

PMID- 12064120
TI  - Contralateral patellar tendon autograft for anterior cruciate ligament
      reconstruction.

PMID- 12064121
TI  - Complications of anterior cruciate ligament reconstruction.

PMID- 12064122
TI  - Revision anterior cruciate ligament reconstruction.

PMID- 12064123
TI  - Revision anterior cruciate ligament reconstruction using the contralateral bone
      patellar tendon-bone graft.

PMID- 12064124
TI  - Posterior cruciate ligament: current concepts.

PMID- 12064125
TI  - Pediatric forearm fractures: decision making, surgical techniques, and
      complications.

PMID- 12064126
TI  - Surgical management of pediatric femoral fractures.
AB  - In contrast to adult femoral fractures, there are many ways to treat a child's
      femoral fracture. The differences mainly involve ease of postoperative care and
      small rates of various complications. The surgeon should be familiar with at
      least one of the options for each age range and be adept at performing them to
      provide the best care for children of all ages.

PMID- 12064127
TI  - Legg-Calve-Perthes disease: current concepts.

PMID- 12064128
TI  - Congenital clubfoot.
AB  - Although the etiology of congenital clubfoot remains unknown, reproducible
      pretreatment grading now seems possible. However, the lack of an agreed-on and
      reproducible posttreatment evaluation system still hinders outcome studies of the
      treatment of clubfoot. The literature from about 1970 to 1990 contains
      enthusiastic reports on the correction of congenital clubfoot through extensive
      surgical release procedures. Over time, we have come to recognize the
      complications of such surgery, including recurrence, overcorrection, stiffness,
      and pain (WJ Shaughnessy, MD, P Dechet, MD, HB Kitaoka, MD, Vancouver, BC,
      Canada, unpublished data, 2000). Perhaps because of these findings, there is a
      renewed interest in nonsurgical techniques for the correction of congenital
      clubfoot. Recent studies have documented the effectiveness of the two leading
      techniques involving serial manipulation and cast treatment. The Ponseti
      technique appears to be effective and requires only a reasonable amount of time
      out of the lives of the patient and his or her parents. The technique frequently
      includes some minimally invasive surgery. The Kite and Lovell technique requires
      minimally invasive surgery less often but is more time consuming. French
      investigators and others have introduced new ideas that may reduce the need to
      immobilize the foot. The French approach requires fairly extensive physical
      therapy and demands substantial parental time and attention. It is not yet clear
      that the French technique is more successful in obviating the need for surgery
      than is expertly applied serial manipulation and cast immobilization. It also has
      not been proved that the long-term results of the French technique are better
      than those of serial manipulation and cast immobilization. It is probably that
      unless the French technique is found to substantially decrease the need for
      surgery, it will prove to be less cost effective than serial manipulation and
      cast immobilization. It is likely that a small number of clubfeet will require
      surgery even after expertly applied nonsurgical treatment. However, it is hoped
      that such surgery will be less extensive than procedures commonly performed in
      the recent past.

PMID- 12064130
TI  - Malignant bone tumors.

PMID- 12064129
TI  - Evaluation of children with suspected cervical spine injury.
AB  - The evaluation of a child with a suspected cervical spine injury differs
      substantially from that of an adult. Knowledge of the developmental anatomy and
      injury patterns is necessary to evaluate and manage these children effectively.
      Improved imaging techniques are facilitating the radiographic evaluation of such
      patients, and the understanding of trauma patterns and how these patterns
      influence the stability of the cervical spine is increasing. With the growing
      awareness of the pathoanatomy and natural history of these injuries, it will be
      possible to manage the issues related to the cervical spine in children more
      effectively.

PMID- 12064131
TI  - Benign bone tumors.

PMID- 12064132
TI  - New frontiers in elbow reconstruction: total elbow arthroplasty.

PMID- 12064133
TI  - Surgical treatment of benign bone tumors.

PMID- 12064134
TI  - Incidental bone lesions.

PMID- 12064135
TI  - Fractures through bone cysts: unicameral bone cysts, aneurysmal bone cysts,
      fibrous cortical defects, and nonossifying fibromas.

PMID- 12064137
TI  - Current concepts of nonpharmacologic thromboembolic prophylaxis.

PMID- 12064136
TI  - Prevention and treatment of thromboembolic disease: an overview.

PMID- 12064138
TI  - Venous thrombosis prophylaxis with low-molecular-weight heparin in hip and knee
      arthroplasty.

PMID- 12064139
TI  - Warfarin prophylaxis for orthopaedic venous thromboembolic disease.

PMID- 12064140
TI  - The use of allografts in musculoskeletal oncology.

PMID- 12064141
TI  - The use of allografts in orthopaedic surgery.

PMID- 12064142
TI  - The use of allografts in sports medicine.

PMID- 12064143
TI  - Antimicrobial resistance: guidelines for the practicing orthopaedic surgeon.

PMID- 12064144
TI  - Elbow instability: treatment strategies and emerging concepts.
AB  - Elbow stability relies on a complex interaction between the bony articulations of
      the elbow joint, the capsuloligamentous structures, and dynamic muscle
      restraints. Understanding the functional anatomy of the elbow and the relative
      contribution of the various elements to elbow stability is important in
      developing a strategy for diagnosis and management. Elbow instability presents a
      spectrum from minor subluxation to dislocation. The treatment of an acute
      dislocation is determined by the stability of the elbow after reduction and the
      fixation of associated fractures. Isolated acute tears of the LCL are uncommon
      and are generally treated nonsurgically. On the medial side, augmented repair is
      required for return to throwing sports. Chronic MCL insufficiency results in
      valgus instability, which usually is a problem only for the throwing athlete.
      Chronic LCL insufficiency may lead to symptomatic posterolateral joint
      subluxation. Free tendon graft reconstruction can be successful on both sides of
      the joint, with a return of stability and improved elbow function.

PMID- 12064146
TI  - Prophylactic antibiotics in clean surgery.

PMID- 12064145
TI  - Antibiotic therapy for musculoskeletal infections.

PMID- 12064147
TI  - Osteoporosis and prevention of fractures: practical approaches for orthopaedic
      surgeons.

PMID- 12064148
TI  - Nonreplacement reconstruction of the elbow joint.

PMID- 12064149
TI  - Elbow arthroscopy: basic setup and treatment of arthritis.

PMID- 12064150
TI  - The role and results of proximal modularity in primary total hip replacement.

PMID- 12064151
TI  - Tapered stems in cemented primary total hip replacement.

PMID- 12064152
TI  - The removal of cementless total hip femoral components.

PMID- 12064153
TI  - Intraoperative angiography evaluation of the microsurgical clipping of unruptured
      cerebral aneurysms.
AB  - Intraoperative angiography evaluation of the clippings of cerebral aneurysms was
      investigated in a series of 38 consecutive patients with unruptured cerebral
      aneurysms to determine any favorable impact on the outcome. Unexpected findings
      including major arterial occlusion or residual aneurysm were identified. Specific
      variables such as the size and site of aneurysm were analyzed to determine the
      impact on clinical outcome and the incidence of clip modification. There were 11
      large and 27 small aneurysms in this series. Mortality and permanent morbidity
      after microsurgical clipping were 0.0% and 2.6%, respectively. Unexpected
      angiographic findings necessitating clip repositioning consisted of residual
      aneurysm in two cases and distal branch occlusion or parent vessel stenosis in
      four. The need for clip modification was significantly higher for large than for
      small aneurysms (p = 0.007), and the rate of clip adjustment increased with
      increasing aneurysm size (p = 0.008). Intraoperative assessment prior to wound
      closure allows for the recognition and correction of defects and decreases the
      risk of postoperative complications. Intraoperative angiography may become
      important in the microsurgical clipping of unruptured cerebral aneurysms,
      especially large aneurysms.

PMID- 12064154
TI  - Technical considerations of transsphenoidal removal of fibrous pituitary adenomas
      and evaluation of collagen content and subtype in the adenomas.
AB  - Pituitary adenomas are usually soft, but 5-13.5% are fibrous adenomas which are
      difficult to remove. Magnetic resonance (MR) imaging and operative findings were
      evaluated in eight patients (12.1%) with fibrous pituitary adenoma among 66
      patients. Tumor specimens were examined histologically and immunohistochemically
      for collagen content and subtypes. Seven patients had clinically inactive non
      functioning pituitary adenomas and one patient growth hormone-secreting adenoma.
      All patients underwent transsphenoidal surgery. Four cases were giant adenomas
      with suprasellar extension of more than 2 cm. T1- and T2-weighted MR imaging
      showed the tumors as nearly isointense to the surrounding brain, except in one
      case where the tumor was high intense on T2-weighted MR imaging. All tumors
      required piecemeal resection using a micro-dissector and tumor forceps. Four
      tumors of maximum size more than 3 cm needed a second operation. The interface
      between the thinned normal pituitary gland and fibrous adenoma was intended to
      identify at the anterior-superior portion in recent four cases, which was helpful
      to remove the tumors and preserve pituitary functions. Histological examination
      revealed prominent deposition of collagen in the perivascular area. The
      percentage of collagen content in fibrous adenomas was more than 5% and
      significantly higher than that in soft adenomas and normal pituitary glands.
      Immunohistochemical examination showed positive staining for collagen types I and
      III in the fibrous adenomas, but only for type V collagen in the normal pituitary
      glands. Large fibrous adenomas can be resected by transsphenoidal surgery which
      may require two-stage operations. Identification of the interface between the
      normal pituitary gland and adenoma is helpful to remove fibrous adenomas and to
      preserve pituitary functions. We propose that firm adenomas containing more than
      5% collagen are "fibrous" adenomas.

PMID- 12064155
TI  - Ruptured dissecting anterior inferior cerebellar artery aneurysm--case report.
AB  - A 39-year-old woman presented with a rare dissecting aneurysm of the proximal
      anterior inferior cerebellar artery (AICA). She presented with sudden onset of
      headache and vomiting, and subsequently became comatose with acute respiratory
      distress syndrome. Computed tomography showed subarachnoid hemorrhage and
      ventricular dilation. Left vertebral angiography identified a fusiform aneurysm
      at the proximal portion of the left AICA. The patient underwent endovascular
      treatment using Guglielmi detachable coils. The aneurysm was completely
      embolized. Computed tomography detected no infarcted areas in the regions
      supplied by the AICA. She was discharged without neurological deficits.

PMID- 12064156
TI  - Dural arteriovenous fistula involving the superior sagittal sinus following sinus
      thrombosis--case report.
AB  - A 57-year-old woman presented with a dural arteriovenous fistula (AVF) involving
      the superior sagittal sinus (SSS) based upon serial radiological examinations.
      Her chief complaints were headache and vomiting. Cerebral angiography and
      magnetic resonance (MR) venography revealed the sinus thrombosis involving the
      SSS, the bilateral transverse sinuses (TSs), and the right sigmoid sinus. Her
      symptoms disappeared after anticoagulant therapy. Follow-up MR venography
      revealed almost complete recanalization of the occluded sinuses, followed by
      restenosis of the SSS and the left TS and occlusion of the right TS without
      symptoms. She developed transient right hemiparesis 13 months after the initial
      onset. Cerebral angiography revealed a dural AVF involving the SSS with cortical
      reflux into the left frontoparietal region. The dural AVF was occluded by
      transarterial and transvenous embolization. Her symptom disappeared during the
      follow-up period.

PMID- 12064157
TI  - Traumatic lesions of the bilateral middle meningeal arteries--case report.
AB  - A 44-year-old man presented with traumatic injuries of the bilateral middle
      meningeal arteries after a traffic accident. Neurological examination found left
      visual impairment due to left optic nerve injury. Computed tomography
      demonstrated a small amount of left epidural hemorrhage and bilateral skull
      fractures. Left external carotid angiography revealed a pseudoaneurysm of the
      left middle meningeal artery at the sphenoid ridge. Right external carotid
      angiography demonstrated a dural arteriovenous fistula fed by the right middle
      meningeal artery colocated with the right frontal convexity fracture.
      Transarterial embolization of the left middle meningeal artery pseudoaneurysm
      with four fibered platinum coils and transarterial embolization of the right
      dural arteriovenous fistula with poly(2-hydroxyethyl methacrylate-co-methyl
      methacrylate) were performed, resulting in complete obliteration of both lesions.
      Angiographic cure was obtained and the postoperative course was uneventful.

PMID- 12064158
TI  - Rapid regrowth of solitary subependymal giant cell astrocytoma--case report.
AB  - A 48-year-old female presented with a subependymal giant cell astrocytoma (SEGA)
      without tuberous sclerosis manifesting as memory and mental disturbance. Magnetic
      resonance imaging showed a huge mass which was well-demarcated and extended from
      the anterior horn of the right lateral ventricle to the septal area on the right
      side. Surgery was performed with partial removal of the tumor. The histological
      diagnosis was typical SEGA. One year postoperatively, follow-up magnetic
      resonance imaging revealed marked regrowth of the tumor. Total resection of the
      tumor was performed. Microscopic and immunohistochemical studies could not
      identify the cause of the rapid regrowth. SEGA can regrow rapidly after partial
      removal of the tumor.

PMID- 12064159
TI  - Spontaneous rupture of a presumed colloid cyst of the third ventricle--case
      report.
AB  - An 83-year-old man presented with gait disturbance, dementia, and urinary
      incontinence that had progressed over 2 months. Computed tomography (CT) of the
      brain revealed hydrocephalus due to a well-demarcated, round hyperdense mass in
      the third ventricle, which was not enhanced by contrast agent. Ten days after the
      initial evaluation, CT revealed that the cyst in the third ventricle had
      disappeared. Magnetic resonance imaging revealed spontaneous rupture of the
      lesion and remnants of cyst wall anchored to the anterior roof of the third
      ventricle. Thereafter, the symptoms of hydrocephalus subsided. However, 6 months
      later the patient's condition gradually deteriorated and the ventricles dilated
      without any evidence of tumor regrowth. Surgical intervention was not performed
      as the family of the patient withheld consent. The natural history of colloid
      cysts of the third ventricle remains unclear. Spontaneous rupture of a presumed
      colloid cyst of the third ventricle should be considered when planning treatment.

PMID- 12064160
TI  - Large giant cell reparative granuloma of the petrous bone--case report.
AB  - A 41-year-old man presented with a large mass bulging over the suprazygomatic
      temporal region. Neuroradiological examination showed that the huge extra-axial
      mass with osteolytic character originated from the upper surface of the petrous
      bone. Preoperative obliteration of the feeding arteries with super-selective
      intravascular embolization was helpful for the total removal of the tumor.
      Histological examination revealed that the tumor consisted of massive
      fibrohistiocytic proliferation with numerous heavily hemosiderin-laden
      macrophages and numerous multinucleated giant cells. The most probable diagnosis
      was giant cell reparative granuloma. Therefore, no postoperative irradiation or
      other adjuvant therapy was given.

PMID- 12064161
TI  - Upper plexus thoracic outlet syndrome--case report.
AB  - A 47-year-old right-handed female became aware of proximal ache and muscle
      weakness in the right shoulder and elbow in 1997. Atrophy of the right biceps
      muscle was recognized and the right deltoid, triceps, supraspinatus, and
      infraspinatus muscles were weak. The Morley test and elevated arm stress test
      were positive. Neurolysis of the brachial plexus and anterior scalenectomy were
      performed via a right supraclavicular approach. An abnormal fibromuscular band
      was identified passing between the upper and middle trunks and constricting the
      middle trunk. Another scalene muscle anomaly was found passing between the C-5
      and C-6 nerve roots and connecting the anterior and middle scalene muscles. These
      muscles were resected, and thorough neurolysis was performed around all nerves
      and the trunks. Postoperatively, all symptoms completely resolved and the patient
      was discharged 5 days after surgery. Thoracic outlet syndrome (TOS) manifests as
      symptoms of lower cervical nerve involvements with hypesthesia and paresthesia.
      However, upper plexus TOS manifests as symptoms due to the involvement of the C-5
      to C-7 nerve roots, and is relatively rare. Transaxillary first rib resection is
      performed as the primary operation for TOS, but supraclavicular scalenectomy is
      effective for upper plexus TOS.

PMID- 12064162
TI  - The role of neurosurgeons in the era of endovascular treatment of cerebral
      aneurysms.

PMID- 12064163
TI  - An introduction to biosecurity of cattle operations.
AB  - Recent world events have heightened awareness for the need to safeguard our
      livestock industries from disease agents. Biosecurity is the outcome of all
      activities undertaken to preclude introduction of disease agents into an animal
      population. The concepts of biosecurity are not new. Activities directed at
      ensuring biosecurity include controlling exposure and optimizing resistance.
      Programs for biosecurity must be individually tailored to specific situations to
      account for varying risks and perceptions of risk by decision makers. It is
      important for practitioners to take a holistic approach to disease control,
      considering the epidemiology of the disease in addition to the available vaccines
      and therapeutics.

PMID- 12064164
TI  - Biosecurity for mammary diseases in dairy cattle.
AB  - As US dairies grow ever larger and obtain replacement animals from a wide
      geographical area, biosecurity will loom ever more important as a means of
      controlling mammary disease. To prevent costly outbreaks of contagious mastitis,
      introduced animals must be screened for contagious IMI before the resident herd
      is exposed to them. Screening programs must be instituted to detect the
      appearance of contagious IMI as soon as possible after introduction has occurred.
      Most importantly, 40 years of knowledge regarding the on-farm control of
      contagious mastitis (now known as with-in-herd biosecurity) must be dusted off
      and implemented with renewed vigor to prevent the rampant spread of contagious
      mastitis.

PMID- 12064165
TI  - Biosecurity of veterinary practices.
AB  - Hospitalization of sick animals tremendously increases their risk of acquiring
      infections as this congregates animals that are most likely to be shedding
      infectious agents with animals that often have enhanced susceptibility. In order
      to provide the best veterinary care possible, veterinarians have an underlying
      responsibility to minimize the risk of additional harm that might unintentionally
      befall a patient because of their interventions. This includes minimizing the
      risk of exposing patients to infectious agents. It is therefore incumbent upon
      veterinarians to actively manage the risk of nosocomial infections. Nosocomial
      infections in veterinary hospitals are not solely a patient-care concern; the
      spread of infectious agents can also significantly impact normal hospital
      operations, revenue, client confidence, public image, and can even affect the
      morale of hospital personnel. In some cases nosocomial agents can also be
      zoonotic. This paper discusses the need for biosecurity programs in veterinary
      practices, and describes a practical approach for developing biosecurity
      practices that are tailored to individual facilities.

PMID- 12064166
TI  - Epidemiologic tools for biosecurity and biocontainment.
AB  - Quantitative models simplify reality, and therefore may misrepresent it. With
      that caution, models can be useful for predicting the outcomes of a variety of
      what-if scenarios related to biosecurity and biocontainment. Graphic
      representations of the models help to visualize relationships between factors
      that influence biosecurity that might not be obvious otherwise. The examples in
      this article illustrate only a few of many epidemiologic relationships relevant
      to biosecurity and biocontainment. Many other relationships remain to be
      explored.

PMID- 12064167
TI  - Protecting US cattle. The role of national biosecurity programs.
AB  - The bovine practitioner has a critical role to play in promoting biosecurity at
      both the farm level and the national level. Successful exclusion of exotic
      diseases, biocontainment of endemic diseases, and emergency preparedness rest
      soundly on bovine practitioners as part of the national biosecurity team. Bovine
      practitioners must voice their opinions on the strengths and weaknesses of
      existing and proposed national biosecurity programs. Healthy debate about
      national biosecurity programs and consideration of biosecurity issues by national
      veterinary organizations provide valuable feedback for the continual improvement
      of the programs and enhance their credibility. The health and productivity of US
      agriculture depend on national biosecurity.

PMID- 12064168
TI  - Biosecurity for gastrointestinal diseases of adult dairy cattle.
AB  - As biosecurity management strategies are developed and implemented to prevent
      introduction and spread of infectious diseases in cattle populations, it is
      informative to review principles of biosecurity from another livestock species in
      which these issues have been considered (e.g., swine) and compare these
      perspectives to the current situation for cattle. The authors follow a
      biosecurity risk-assessment model to identify important health hazards, evaluate
      risks, and present principles for implementing a cattle biosecurity program for
      important gastrointestinal health hazards of adult dairy cattle, after
      consideration of a swine biosecurity model.

PMID- 12064169
TI  - Biosecurity and bovine respiratory disease.
AB  - Although biosecurity practices play a role in minimizing respiratory disease in
      cattle, they must be used in combination with other management strategies that
      address the many other risk factors. Because the pathogens involved in bovine
      respiratory disease are enzootic in the general cattle population, biosecurity
      practices aimed at the complete elimination of exposure are currently
      impractical. Several animal husbandry and production management practices can be
      used to minimize pathogen shedding, exposure, and transmission within a given
      population, however. Various combinations of these control measures can be
      applied to individual farms to help decrease the morbidity and mortality
      attributed to respiratory disease.

PMID- 12064171
TI  - Biosecurity for reproductive diseases.
AB  - Application of rational principles of risk management in designing an effective
      biosecurity plan for reproductive diseases can be an important part of a
      profitable operation. Knowledge of the disease status of the particular herd, the
      effective strategies for disease exclusion including test performance and
      reservoirs is necessary. Vaccination can be an effective part of a biosecurity
      program by increasing herd immunity and decreasing the impact of an outbreak, but
      by itself will not prevent infections and losses. A more comprehensive approach
      to disease control is needed. Development and implementation of a biosecurity
      program is an individualized effort undertaken for a particular operation.
      Knowledge of the disease status of the herd for each agent of concern and
      prioritization of the diseases most important in the herd is necessary. The
      biosecurity plan is then specific for the herd and the particular agent(s) of
      concern. Practitioners can apply knowledge of the epidemiology and ecology of
      disease agents to identify and implement logical control points for the
      individual herd. Many control strategies may be effective for more than one
      disease. A comprehensive look at the operation is necessary to make sure that the
      cost of the biosecurity plan does not exceed the return in prevented disease and
      increased production over the planning period.

PMID- 12064170
TI  - Biosecurity for neonatal gastrointestinal diseases.
AB  - Infectious diarrhea is an important cause of neonatal calf morbidity and
      mortality that results in significant economic losses in the beef and dairy
      industries. Although numerous risk factors related to the occurrence of neonatal
      diarrhea have been identified, they can all be categorized into those that are
      related to the calf, the pathogens involved, or the environment of the calf. The
      immune status of calves, specifically the level of passively acquired immunity
      through colostrum, is the major risk factor related to the calf and the
      occurrence of diarrhea. Although numerous pathogens have been implicated in the
      occurrence of neonatal diarrhea, only a relatively limited number are commonly
      involved. Most should be viewed as secondary opportunists rather than primary
      pathogens, because none are extraordinarily virulent, and with the exception of
      Salmonella spp., most are present within the gastrointestinal tract of many
      healthy, mature cattle. Important risk factors related to pathogens involved in
      neonatal calf diarrhea involve the size of the inoculum and the occurrence of
      multiple infections. Finally, when considering the environment and housing
      conditions in which beef and dairy calves may reside, it is clear that tremendous
      variations exist. Despite these variations, the risk factors associated with the
      environment of the calf are also those that are the most amenable to the
      implementation of general environmental control and monitoring strategies as well
      as specific biosecurity measures.

PMID- 12064172
TI  - Biosecurity for arthropod-borne diseases.
AB  - Arthropod-borne diseases (ABD) of cattle include those pathogens transmitted
      mechanically and biologically from one bovine to another or from other species to
      cattle. This article provides examples of the more common ABD of North America
      and reviews strategies to prevent entry of ABD onto cattle operations and control
      transmission of ABD once established on cattle operations using an integrated
      approach.

PMID- 12064173
TI  - Diagnosing and treating pain in the horse. Where are we today?
AB  - This chapter begins by providing an overview of current philosophies relevant to
      equine pain management. Objective and subjective techniques for assessing pain
      and the limitations of these are then described in depth. The conclusion
      emphasizes the need for an evidence based approach to managing pain in the horse
      and sets the stage for subsequent chapters in this edition.

PMID- 12064174
TI  - The role of complementary techniques in managing musculoskeletal pain in
      performance horses.
AB  - The locomotor system requires normal movement for normal function. Movement
      restrictions of soft tissues and joints stimulate nociceptive pathways in the
      corresponding vertebral segment. Reflex-induced alterations of sensory and motor
      neuron activity within the segment lead to detrimental changes within many of the
      tissues associated with and distant from the area. Manual therapy is utilized in
      both diagnosis and treatment of tissue and joint movement restrictions. Early
      recognition and treatment of dysfunction in the equine athlete prevents permanent
      pathology and facilitates performance excellence.

PMID- 12064175
TI  - Management of equine orthopedic pain.
AB  - Pain management is an extremely vital part of equine orthopedic surgery.
      Providing optimum analgesia for the patient will decrease recovery time, decrease
      physiologic stress on the animal, and provide maximum comfort during the post
      operative period. The major analgesic drug categories and routes covered are
      nonsteroidal anti-inflammatory drugs, local anesthetics, intra-articular drugs,
      and epidurals.

PMID- 12064176
TI  - Management of gastrointestinal pain.
AB  - Choice of an analgesic for gastrointestinal pain requires consideration of the
      cause of the pain, desired duration of pain relief, need for sedation, and
      potential side effects and toxicity, particularly in light of other drugs being
      used and effects on the gastrointestinal tract. It is imperative that close
      monitoring be continued to ensure that surgical lesions or worsening conditions
      are detected. Recent research in the field may lead to new drugs, drug
      combinations, and avenues of treatment that minimize the side effects of these
      drugs while maximizing their efficacy.

PMID- 12064177
TI  - Recent advances in inhalation anesthesia.
AB  - Both desflurane and sevoflurane offer theoretical and practical advantages over
      other inhalation anesthetics for horses. The lower solubility of both agents
      provides improved control of delivery and helps to counteract the confounding
      influence of the voluminous patient breathing circuit commonly used for
      anesthetizing horses. The lower solubility should account for faster rates of
      recovery compared with the older agents; whether or not the quality of recovery
      differs remains to be objectively evaluated in a broad range of circumstances.
      The pharmacodynamic effects are, in large part, similar to those of isoflurane
      (e.g., low arrhythmogenicity) but with some differences. For example, desflurane
      may be overall more sparing to cardiovascular function (especially during
      controlled ventilation) compared with isoflurane and sevoflurane, which are
      roughly similar. Respiratory depression with both new agents is equal to or more
      depressing than isoflurane, suggesting the use of mechanical ventilation,
      especially in circumstances of prolonged management (i.e., hours of anesthesia).
      Both new anesthetics, not surprisingly, are expensive. From this point there are
      some agent-unique considerations. The anesthetic potency of both agents is less
      than that of isoflurane, which influences the cost of anesthesia, but also places
      an upper limit on inspired oxygen concentration (of particular concern with
      desflurane). Both agents require new vaporizers, but because of the high boiling
      point and steep vapor-pressure curve of desflurane, new technology was required.
      This translates into more costly equipment, adding to the cost of desflurane use.
      In addition, electricity is necessary for the new desflurane vaporizer to
      function, which limits its portability and adds additional practical
      considerations in its clinical use. On the other hand, desflurane strongly
      resists degradation both in vitro and in vivo, but in vitro degradation of
      sevoflurane by CO2 absorbents may produce renal injury. This may be true
      especially in association with low fresh-gas inflow rates (used to reduce the
      cost of using the new agent), and university based practices, where prolonged
      anesthesia is common.

PMID- 12064178
TI  - Traditional and non-traditional uses of anesthetic drugs--an update.
AB  - Many new or modified injectable anesthetic techniques are available for use in
      horses. This increased availability allows the clinician to select the technique
      most appropriate for the patient and clinical circumstance. The use of sedative
      and anesthetic drugs in managing a variety of anesthesia-related and unrelated
      aspects of patient care is also increasing. As we begin to use these techniques
      in the clinical management of our patients, it is important to remember that,
      while there are more options, no single anesthetic agent or combination of agents
      is devoid of undesirable effects. Knowledge of the pertinent advantages and
      disadvantages of the drugs when used individually and in combination and
      appropriate patient monitoring are essential to ensure a positive outcome.

PMID- 12064179
TI  - Neuromuscular blocking agents.
AB  - In summary, with proper vigilance, neuromuscular blocking agents can be used
      safely in anesthetized equine patients to optimize conditions for certain
      surgical procedures. By appropriate use of neuromuscular monitoring techniques
      and reversal agents, residual blockade and muscle weakness should be avoided,
      allowing the horse to recover to standing without difficulty. Research is ongoing
      to develop the ideal muscle relaxant, one that has a rapid onset, predictable
      duration and recovery times, and negligible hemodynamic effects. As newer agents
      become available, they should be evaluated for their suitability for use in
      equine patients.

PMID- 12064180
TI  - Nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are substances other than steroids
      that inhibit a component of the inflammatory cascade. This article is dedicated
      to those substances which specifically inhibit cyclooxygenase. NSAIDs are used
      extensively in the veterinary field. This article discusses their pharmacologic
      mechanism of action, indications, and toxicity. The two isoforms of
      cyclooxygenase (COX-1 and COX-2) are reviewed along with the newer NSAID which
      are more effective and less toxic due to more specific COX-2 inhibition. Specific
      effects on soft tissue, bone, cartilage, and synovium are summarized. Pain
      modulation is extensively reviewed as well as the antiendotoxic and
      antithrombotic uses.

PMID- 12064181
TI  - Alpha-2 adrenergic agonists as analgesics in horses.
AB  - Administration of alpha-2 agonists to horses produces a variety of behavioral
      effects (sedation, somnolence, analgesia), and physiological effects. One of the
      most significant beneficial effects of administering alpha-2 agonists is the
      degree of analgesia they provide. Alpha-2 agonists have been the mainstay of
      analgesia for colic pain in horses since their introduction to clinical
      veterinary medicine. The increased potency of the more recently introduced alpha
      2 agonists allows the provision of analgesia for conditions not previously
      relieved by other drugs. Unfortunately, there are significant side effects
      associated with alpha-2 agonist administration. Studies are underway to identify
      the physiologic effects associated with the stimulation of each alpha-2 receptor
      subtype, in hopes of developing subtype-specific alpha-2 agonists and
      antagonists.

PMID- 12064182
TI  - Use of opioids for pain and anesthetic management in horses.
AB  - REGIONAL ADMINISTRATION: There is limited, but convincing, evidence that epidural
      administration of morphine and some other mu-agonist opioids consistently
      relieves regional pain in horses. In addition, this effect is not accompanied by
      notable undesirable effects. On the other hand, a clinically important analgesic
      action has not been demonstrated for similarly administered kappa-agonist
      opioids. There has been little objective data presented to support the analgesic
      effectiveness of intra-articularly administered opioids in horses. However, the
      evidence of local opioid receptors legitimately encourages work to substantiate
      the value of intra-articular opioid administration to relieve joint-associated
      pain in horses. SYSTEMIC ADMINISTRATION: So far, study results do not provide
      convincing, objective evidence to support the opinion that systemically
      administered opioids consistently and effectively relieve pain in horses. Given
      this lack of evidence, and considering that opioids stimulate locomotor and other
      forms of unwanted excitant behavior, reduce propulsive gastrointestinal motility,
      decrease alveolar ventilation (especially in association with general
      anesthesia), and require regulatory and practical considerations for abuse
      potential in both humans and horses, we conclude that routine, indiscriminate
      administration of opioids for pain relief in horses is not justified.
      Identification and focused, objective study of selective beneficial opioid
      actions to provide guidance for appropriate clinical use is long overdue.

PMID- 12064183
TI  - Epidural anesthesia and analgesia in horses.
AB  - Intercoccygeal, or caudal, epidural injection of local anesthetics is a
      convenient method of producing analgesia and local anesthesia of the tail and
      perineal structures in conscious standing horses. This technique has been further
      developed to provide long duration analgesia and anesthesia by placement of
      catheters into the epidural space of horses. More recently, opioid, alpha-2
      adrenergic agonists, ketamine and other analgesic agents have been administered
      by caudal epidural injection, providing pain relief in both conscious, standing
      and anesthetized, recumbent horses. This chapter describes the development of
      different anesthetic and analgesic epidural techniques in horses, methods for
      epidural injection and catheterization, and reviews the current literature
      related to epidural analgesia and pain control in horses.

PMID- 12064184
TI  - Nontraditional approaches to pain management.
AB  - The word nontraditional in the context of this article implies those modalities
      not normally taught in veterinary medical schools. This word has the same
      definition of Complementary and Alternative Medicine (CAM) as put forth by the
      Harvard medical school. CAM is a field of medicine that has enjoyed a recent
      increase in popularity in both human and equine medicine, particularly in regard
      to pain management. Some of the more recognized modalities include acupuncture,
      herbalism, and homeopathy. A brief discussion regarding the theory, scientific
      evidence and use of these therapies in the treatment of pain will be discussed.

PMID- 12064185
TI  - [Diabetes mellitus and stroke].
AB  - Ischemic stroke represents the third mortality cause after cardiac diseases and
      tumors and the relationship between diabetes and stroke incidence is still
      unclear. Several studies (Framingham, Copenhagen Stroke Study, Northern Sweden
      MONICA, NHANES) showed a higher prevalence, recurrence rate and worse prognosis
      of stroke in diabetic subjects. As for cerebral ischemia pathogenesis small
      vessel disease of deep perforating arterioles plays a crucial role although the
      higher cerebrovascular risk is also related to the additional risk factors and
      the characteristic atherogenic diabetic profile. Significant appears the
      pathogenetic role of acute hyperglycemia as a direct neuronal damage mediator and
      negative prognostic marker. On the basis of epidemiological data, cerebrovascular
      risk prevention in diabetic subjects consists of secondary prevention strategies
      regarding glycemic control, vascular protection by ramipril and perindopril,
      statins and antiplatelet drugs like acetylsalicylic acid and clopidogrel as shown
      by randomized trials (UKPDS, DCCT, HOPE, PROGRESS, 4S, WOSCOPS, CARE, LIPID,
      CAPRIE, etc.).

PMID- 12064186
TI  - [Hemodynamic progression of aortic valve stenosis in the adult: implications of
      the clinical management of asymptomatic patients].
AB  - In this review the issue of the progression of hemodynamic severity of
      asymptomatic aortic stenosis is analyzed. The role of several factors leading to
      faster progression of the disease is discussed. The knowledge of these findings
      is very helpful in order to evaluate the best strategy of follow-up in these
      patients. Another important point to clarify is the management of patients with
      mild or moderate aortic stenosis undergoing coronary artery bypass graft surgery.

PMID- 12064187
TI  - [Mitral insufficiency].
AB  - Over the past 15 years, outcome of patients with severe mitral insufficiency is
      significantly improved. This may be due to concomitant advances in many fields of
      medicine such as a more effective diagnosis and left ventricular function
      monitoring by means of echocardiography, development of useful guidelines and
      advances in valve reconstruction techniques. We will discuss some aspects of
      mitral anatomy, pathophysiology, echocardiographic diagnosis and the proper
      timing for surgical intervention.

PMID- 12064188
TI  - [Oral anticoagulants combined with aspirin in the prolonged treatment after acute
      coronary syndrome].
AB  - The incidence of death or myocardial infarction after acute coronary syndrome
      (ACS) is still high despite the widespread use of aspirin. Oral anticoagulant
      therapy (OAT) reducing thrombin activity has the potential to be beneficial when
      administered alone or in combination with aspirin after ACS. Low-intensity OAT in
      combination with aspirin is not superior to aspirin alone. Moderate-intensity OAT
      in combination with aspirin is superior to aspirin alone in reducing death,
      myocardial infarction or stroke after ACS. However, this regimen has higher rates
      of both minor and major hemorrhages. The bleeding risk combined with the
      difficulties of OAT management contributes to suboptimal compliance and has the
      potential to mitigate the superior efficacy of combined regimens.

PMID- 12064189
TI  - [Current management of oral anticoagulant treatment].
AB  - In recent years oral anticoagulant therapy has been recommended to an increasing
      number of patients for the primary or secondary prevention of thromboembolic
      diseases. Optimal management includes patient's education, adequate laboratory
      and specific clinical control. In this review, together with basic knowledge,
      data from medical literature are used to provide guidelines and practical
      information for the management of these patients.

PMID- 12064190
TI  - [Cost reduction in the assessment of thoracic pain with the chest pain unit in
      first aid].
AB  - BACKGROUND: The evaluation of chest pain is a constant challenge for
      cardiologists, due to its clinical, organizational, economical and legal
      implications. The costs of the diagnostic classification of non-specific thoracic
      pain during ordinary, albeit short, hospitalization are here compared with a
      quick screening of the same symptoms in a "Chest Pain Unit", which may form an
      appendix of the emergency room (ER). METHODS: The study involves patients
      admitted to the hospital used as reference during the year 2000 and discharged
      with a diagnosis of thoracic pain or precordial pain, as identified by ICD-9-CM
      codes 786.50, 786.51, 786.52, 786.59. According to DRG 143 tariffs, the
      hospitalization of such a patient costs Itl 4,346,000 epsilon 2244.52). If a
      Chest Pain Unit should monitor the same patients in the ER for at least 12 hours,
      during which time the examination at admission has to followed by two ECGs, 4
      seriated evaluation of cardio-specific enzymes, an echocardiogram and a stress
      test, the individual cost concerning payment for ER services, would be of Itl
      879,000 ([symbol: see text] 453.97). Even adding Itl 508,000 ([symbol: see text]
      262.36) to pay the 12-hour monitoring provided for by the short protocol, the
      total amount would be Itl 1,387,000 epsilon 716.33). This evaluation has also
      been applied to the 47,775 patients hospitalized with the same diagnosis in all
      Italian hospitals during the year 1999. RESULTS: Three hundred and thirty-eight
      patients admitted to the hospital used as reference were discharged with the
      above reported diagnosis. Among them 215 (64%) were hospitalized in the
      cardiology ward. The total cost for hospitalization for the 338 patients
      evaluated was Itl 1,468,948,000 epsilon 758,648.33) as compared to Itl
      297,102,000 epsilon 153,440.37) that the short-term therapy would have required.
      Countrywide the same cost was Itl 207,543,230,000 epsilon 107,187,132.99) as
      compared to Itl 41,976,645,000 epsilon 21,679,127.91) for the short-term therapy,
      using which would have led to save Itl 166,566,585,000 epsilon 86,024,461.98).
      CONCLUSIONS: The suggested strategy, corroborated by many previous experiences,
      is an effective and efficient alternative for thoracic pain evaluation,
      especially in a time when economical resources are being drastically reduced,
      thus requiring research and application of optimized diagnostic procedures.

PMID- 12064191
TI  - [Role and interactions of the cardiologist in a regional institutional project of
      primary prevention].
AB  - BACKGROUND: Evidence is available in support of the policies for a population
      wide approach to shifting risk factor distribution; on the other side, setting up
      enduring projects of primary prevention is difficult, as well as gathering the
      right experts. METHODS: In 1999 the Piedmont Region's Administration set up a
      multi-year intervention with the aim at reducing risk factors and increasing
      protective factors of oncologic and cardiovascular diseases in the general
      population, particularly in disadvantage groups. The cardiologists played a
      primary role by supporting the project of evidence-based guidelines, producing
      bibliographic reviews and spreading coronary risk maps. A main group of trainers
      was set up in each Local Health Service to promote a system of counseling
      lifestyles, with the central reference of the general practitioner activity. As a
      second step, a mass-media campaign has been set up using health advertisements on
      newspapers, television, public transports, notice-boards on the following
      subjects: nutrition, hypertension, tobacco, physical activity, stress;
      warehouses, food markets, trains and squares were involved. Moreover, a
      newsletter review has been published since January 2000, to produce basic models,
      most effective interventions and recommendations for their implementation.
      RESULTS: A new care for the primary prevention and counseling arguments as well
      as the need for continuous training to promote preventive actions were shown to
      general practitioners. A system to identify the best channels, communication ways
      and the most effective messages for healthy lifestyles was settled. A model of
      monitoring risk factor changes and protective behaviors in the population,
      describing social differences, was established to better plan and assess
      effective interventions. CONCLUSIONS: After more than half a century of
      productive public health science, there is an urgent need that Government
      Administrations steer their health policies towards determinants of health and
      create the best conditions to make citizens to improve their lifestyle.

PMID- 12064192
TI  - [Impact of a nurse-based heart failure management program on hospitalization
      rate, functional status, quality of life, and medical costs].
AB  - BACKGROUND: Chronic heart failure is a major health problem for prevalence,
      morbidity and costs; heart failure management programs may prevent hospital
      admissions, improve clinical status and reduce medical costs. METHODS: A care
      program for chronic heart failure patients was activated by the Cardiology
      Department, based on a nurse-monitored outpatient clinic, ran in cooperation with
      cardiologists, who were responsible for optimal pharmacological treatment. Nurses
      provided patient education, monitoring of clinical status and symptoms and
      verified adherence to pharmacologic and dietary therapy. To assess the impact of
      the program on hospitalization rate, functional status and quality of life we
      compared: 1) hospital admission rate for heart failure in the 6 months before and
      the 6 months after referral; 2) Minnesota Living with Heart Failure Questionnaire
      (MLHFQ) score and NYHA functional class at referral time and after 6 months. A
      cost-based analysis was performed to compare the two periods. RESULTS: Between
      January 1999 and November 2000, 107 patients were followed up for at least 6
      months. Hospitalization declined by 70% (57 admissions in the 6 months before
      referral, 17 in the 6 months afterwards, p = 0.0001). Functional status improved
      after 6 months: 41 patients were in NYHA class III-IV at referral time, 26 after
      6 months. The mean total score of MLHFQ was reduced from 33.9 to 28.7 (p =
      0.005). The average cost of the program was estimated to be [symbol: see text]
      218 (Itl 423,000) per patient in 6 months. The savings in overall cost of care
      was [symbol: see text] 615 (Itl 1,192,000) per patient in 6 months. CONCLUSIONS:
      A management program based on a nurse-monitored outpatient clinic can reduce
      hospitalization rate, improve functional status and quality of life and decrease
      medical costs for chronic heart failure patient's care.

PMID- 12064193
TI  - [Combination therapy for acute myocardial infarction with glycoprotein IIb/IIIa
      inhibitors and fibrinolysis].
AB  - Early achievement of TIMI 3 (normal) flow in the infarct-related artery is the
      goal of therapy of acute myocardial infarction (AMI) in order to reduce infarct
      size and improve clinical outcome. By the mid 1990s mechanical treatment (primary
      angioplasty) has been recognized as the best method to gain this goal but
      fibrinolysis still remains the standard of care because of logistic limitations
      of angioplasty. Benefit of aspirin in association with fibrinolytic drugs
      encouraged the use of antagonists of the glycoprotein IIb/IIIa receptor
      (abciximab, eptifibatide, tirofiban), which block the final common pathway of
      platelet aggregation in AMI therapy. In dose-finding and dose-confirmation
      studies the combination of a fibrinolytic agent with a glycoprotein IIb/IIIa
      receptor antagonist, such as abciximab, resulted in nearly 80% of patients
      achieving complete reperfusion at 90 min without a substantial increase in side
      effects. This combination was tested in the phase III GUSTO V study. Compared to
      full-dose reteplase alone, the association of half-dose of reteplase and
      abciximab significantly reduced most non-fatal complications of myocardial
      infarction such as reinfarction and need of urgent revascularization. Failure to
      show a reduction in mortality with "combo therapy" must be related to the low 30
      day mortality observed in both arms of the study, the lowest ever found in
      fibrinolytic trials. Warning about an increase in non-intracranial bleeding is
      counterbalanced by similar rates of intracranial hemorrhages and non-fatal
      disabling strokes in the two groups. On the basis of the GUSTO V results it
      appears clear that future advances in the management of AMI will only be possible
      by combining different reperfusion modalities (lytics, IIb/IIIa antagonists and
      coronary angioplasty). Whichever is the best combination, mechanical reperfusion
      will play a central role in the management of AMI. A major challenge for
      cardiologists will be reinforcement of collaboration and synergy between
      institutions with different levels of resources.

PMID- 12064194
TI  - [Combination therapy for acute myocardial infarction with glycoprotein IIb/IIIa
      inhibitors and fibrinolysis].
AB  - The best conventional fibrinolytic regimens succeed in restoring unimpeded
      coronary flow (i.e., TIMI grade 3 reperfusion) in only about 50% of lytic
      eligible patients. In experienced hands, percutaneous coronary intervention
      (angioplasty + stent implantation) can restore TIMI 3 flow in more than 80% of
      patients; however, it is not universally available, and usually cannot be
      performed as promptly as fibrinolytic therapy. Researchers now recognize that one
      key reason fibrinolytic therapy fails is that it does not adequately address the
      role of platelets in both the initial formation and posttreatment recurrence of
      coronary thrombus activated, aggregating platelets at the site of plaque fissure
      or rupture form the core ("white" clot) of an intracoronary thrombus. The
      platelets contribute to the further development of a meshwork of fibrin,
      thrombin, and entrapped blood cells ("red" clot), which usually makes up the bulk
      of an occlusive coronary thrombus. Plasminogen activators, such as alteplase and
      reteplase, lyse fibrin in the red thrombus but leave the platelet-rich core
      intact. The glycoprotein (GP) IIb/IIIa antagonists abciximab, tirofiban, and
      eptifibatide bind to GP IIb/IIIa receptors on the surfaces of activated
      platelets. By preventing the receptors from binding to fibrinogen (and, hence, to
      each other) GP IIb/IIIa inhibitors block the "final common pathway" to platelet
      aggregation. Combining fibrinolysis with GP IIb/IIIa blockade to treat acute
      myocardial infarction could, theoretically, yield a number of benefits. It would
      attack both red and white components of the occlusive thrombus, help suppress the
      thrombotic rebound effect of fibrinolytics by preventing platelet activation in
      response to newly exposed thrombin, improve reperfusion and microvascular flow,
      reduce the incidence of postfibrinolytic hemorrhagic stroke (currently
      approximately 1%) if combination therapy permits use of lower dosages of
      fibrinolytic agents. Two phase II trials of fibrinolytic therapy plus GP IIb/IIIa
      blockade have recently been reported. In TIMI 14, the reduced-dose combinations
      of alteplase plus abciximab produced TIMI 3 rates higher than the control group.
      In the TIMI 14 reteplase substudy, TIMI 3 flow rates with reteplase at 90 min was
      70% for standard dose reteplase alone, 70% for reteplase 5 IU + 5 IU plus
      abciximab, and 77% for reteplase 10 IU + 5 IU plus abciximab. In the SPEED pilot
      study the highest TIMI 3 rates was seen with the regimen of 5 IU + 5 IU double
      bolus reteplase plus abciximab (54 vs 47%). The findings of both the SPEED and
      TIMI 14 trials were incorporated into the design of the large (approximately
      17,000 patients) GUSTO V mortality trial, which compared standard reteplase
      therapy with abciximab plus low-dose reteplase. Unfortunately, the results did
      not confirm the favorable angiographic findings of the phase II trials reported
      above, because the two strategies showed the same mortality rate at 30-day follow
      up. The present review will try to shed light on the "dark side of the moon" of
      the association between IIb/IIIa inhibitors and fibrinolytic drugs in order to
      understand the unexpected GUSTO V results, now matched by the ASSENT-3
      disappointing results with tenecteplase plus abciximab.

PMID- 12064195
TI  - [Acute myocardial infarction after wasp sting].
AB  - Myocardial infarction after wasp sting is a rare event and this complication has
      been described in only a few previous occasions. We report the case of a 77-year
      old patient admitted to our hospital because of an anaphylactic shock after he
      was stung by a wasp on the fifth finger of the left hand. Within about half an
      hour he sustained an acute myocardial infarction. Possible pathogenetic
      mechanisms include severe hypotension due to hypovolemic shock and coronary spasm
      with subsequent thrombosis of coronary vessels developed after the release of
      vasoactive, inflammatory and thrombogenic substances contained in the hymenoptera
      venom.

PMID- 12064196
TI  - [Coronary microembolization in acute coronary syndrome: indicative hypothesis or
      still unknown phenomenon? Description of a clinical case].
AB  - Acute myocardial infarction may result from rupture or fissuring of
      atherosclerotic plaque in a coronary artery. Sometimes a different pathogenesis
      occurs like microembolization following lysis from ulcerated plaque or during
      pharmacological or interventional procedures. We describe a patient with anterior
      myocardial infarction treated with alteplase + abciximab (TIMI 14). At the end of
      thrombolytic therapy administration, we observed a marked reduction of anterior
      ST elevation associated with a simultaneous occurrence of ST elevation in the
      inferior leads, later followed by inferior Q waves. The coronary angiogram
      demonstrated an isolated 60% stenosis on the left anterior descending artery.
      This case raises the question on whether the very effective and aggressive
      thrombolytic treatment was paradoxically responsible for microembolization
      resulting in myocardial infarction extension.

PMID- 12064197
TI  - [The use of antiarrhythmia agents to increase the probability of success of
      electric cardioversion in atrial fibrillation].

PMID- 12064198
TI  - [Cleft lip and palate treatment in the plastic surgery department in the
      university hospital center in Lille].
AB  - The aim of cleft care is to favor a normal socialization of patients with fewer
      therapeutic coercion. It supposes a full multidisciplinary team including
      psychologist, speech therapeutic, dental orthopedist, oto-rhino-laryngologist and
      surgeons. All of them have to be well trained which supposes a sufficient amount
      of cases: anglo-saxon studies have proven that a mean of at least 20 new cases
      per year of primary cleft were necessary. With purposes to enhance the
      effectiveness of treatment: prospective studies and measurements of results must
      be evaluated with the help of objective criteria. These are the goals of our team
      in lille. Our surgical principles are those of functional procedures, which
      privilege the muscle function's repair.

PMID- 12064199
TI  - [Cleft lip, maxilla and palate treatment by Dr. Talmant's team in Nantes].
AB  - Over the last 30 years, our private cleft lip and palate team has developed an
      increasing activity based on the Victor Veau's concept: "All the structures are
      present and only deformed". Our goal is to achieve an anatomical and fully
      functional repair in every fields with the first operation. A few recent
      refinements have improved our primary procedures: intravelar veloplasty;
      simultaneous lengthening of the columella and primary lip repair in bilateral
      clefts; nasal retainer for the 3 or 4 first postoperative months allowing the
      establishment of a nasal breathing mode at once. Our timing has been the same
      over the last 21 years if we except that we currently perform the
      gingivoperiosteoplasty between 4 and 5 years of age so that the width and the
      relationships of the maxillary arch are normal at the time of the mixed
      dentition. The timing is the same in uni and bilateral clefts. No preoperative
      orthopedics. At 6 months of age, nasolabial repair and closure of the soft palate
      with intravelar veloplasty. At 18 months of age, anatomical closure of the
      residual cleft of the bony palate in two planes without vomer flap or denuded
      bone. Between 4 and 5 years of age, after a short orthopedic treatment, closure
      of the alveolar cleft by a gingivoperiosteoplasty with iliac bone graft. From 6
      years of age we start the orthodontic treatment. The current evolution allows to
      think that only few late corrections will be necessary.

PMID- 12064200
TI  - [Primary and secondary care of cleft lip and palate in the lip-palate center in
      Bruxelles].
AB  - Since 1987, we chose a neonatal repair of the cleft lip and nose and closure of
      the cleft palate at 3 months of age. Ventilation tubes are systematically
      inserted in the drums at time of palatoplasty. Alveolar clefts are grafted when
      canine erupts. Secondary correction, which might be early, are scheduled
      according to functional, aesthetic or psychological demands. A interdisciplinary
      follow-up by a stable and united team is essential for an adequate management of
      sequels.

PMID- 12064201
TI  - [Treatment of cleft lip and palate in the children's Hospital Reine Fabiola in
      Bruxelles].
AB  - The priority in the treatment of facial clefts is to avoid the iatrogenic
      sequellae by restoring a normal anatomy of the face. The difficulty of this
      treatment is that the majority of the sequellae are only observed 15 years after
      the primary treatment. After having treated our children during more than 20
      years by a primary closure of the lip at 6 months and closure of the palate by
      push back according to Veau Wardill at 18 months, we adopted the technique of
      Rene Malek since 1981 with early closure of the palate at 3 months then, without
      undermining of the palatal mucosa, closure of the bony palate with a vomer flap
      at the age of 6 months. Since 1988, in unilateral complete cleft, we perform a
      complete closure of the lip and palate at 3 months according to the same surgical
      principles. The study of the dental casts according to the Golson Yardstick at
      the age of 10 and the cephalometric study by lateral Xrays at the age of 15 show
      an excellent facial growth in the majority of the cases with only 6% needing a
      osteotomy at the end of growth. Moreover the phonation of these children was very
      good in the majority of the cases, 15% only needing a secondary surgery. The only
      remaining sequellae are in the auditory field with an abnormal frequency of sero
      mucous otitis. These could not be improved until now despite the early use of
      tympanic drains.

PMID- 12064202
TI  - [Care and management of cleft lip and palate by CLP Department hospital Robert
      Debre in Paris].
AB  - Cleft lip and palate repair must take a place at an early stage and respect
      physiology. Iatrogenic consequences harming maxillary growth must be avoided.
      Owing to early and reverse timing, short and long term results have been
      improved. Correction of the soft palate is performed at 3 months of age, lip and
      hard palate at 6 months without elevation of mucoperiosteum. A palatal plate is
      applied before and after each surgical stage. Patients receive phonetic, dental
      end ENT follow-up on a regular basis till end of growth. Correction of sequelae,
      especially of nasal tip, can be undertaken around grade school entrance at about
      6 years of age. Nasal sequelae such as deviation of the septum must not be
      corrected before end of puberty. Surgery and follow-up must be conducted by an
      experienced multi-disciplinary team in which the surgeon plays the part of master
      of works.

PMID- 12064203
TI  - [Clinical management of cleft lip and palate in university hospital of
      Montpellier].
AB  - Management of labio-maxillo-palatine clefts has two major requirements: to
      constitute a multidisciplinary staff (surgical, phonological, orthodontical)
      intervening as soon as possible and determination of a precise therapeutical
      chronology not only for primary surgery but also for sequellae. Primary surgical
      protocol is in cases of total clefts these defined by Malek and Psaume; and for
      pure labial or incomplete clefts, we perform a neonatal surgery. Integration of
      interceptive correction of sequellae into thus protocol appears basic: correction
      of alveolar cleft by gingivoplasty (5 to 7 years) associated with secondary home
      graft between 11 to 13 years; early nasal revision since 2 years for functional
      and aesthetic reasons. Early control of speech development, otologic problems and
      their management appears a very important point. Introduction of the concept of
      maxillary distraction appears to us a very important improvement for correcting
      orthognatic cases with major problems of squeletical growth. Recent introduction
      of the antenatal diagnosis introduces a new concept in psychological approach of
      these cases. It is necessary to establish a network for managing these cases
      since the antenatal period.

PMID- 12064204
TI  - [Management of cleft lip and palate in university hospital of Rouen].
AB  - Cleft lips and cleft palates are managed in the department of Pediatric surgery
      in Rouen for the last 30 years. From the antenatal diagnosis, the parents got in
      touch with the surgeon who will coordinate this management. Around thirty new
      patients are treated every year. The chronology of the treatment is of "classic"
      manner. The cleft lip is repaired at about 3 weeks of age and the palatoplasty is
      performed after the age of 1 year. In view to maintain the intimacy of the
      consultation we did not institute multidisciplinary consultations. The other
      members of the interdisciplinary team will intervene during the follow up
      depending on the form of the cleft and the encountered problems. The information
      and the files circulate freely and are discussed together.

PMID- 12064205
TI  - [Therapeutic approach of cleft lip and palate at Caen University Hospital].
AB  - The therapeutic approach of facial cleft in Caen University Hospital depend on
      two teams: primary treatment by the Pediatric Plastic Unit (60 cases/year), and
      secondary treatment by the department of Plastic and Maxillofacial Surgery (more
      than 30 cases/year). The lip closure is realised before the age of one month with
      the Tennisson's technic. The palate closure is performed between 6 and 12 months
      old. Each patient is presented at a multidisciplinary consultation which include
      a surgeon, an orthodontist, an orthophonist, a psychologist and otologist. At
      about 5 years old, the orthodontic approach begins with palatal expansion with a
      modified quadhelix to prepare function its treatment is underwent at this age
      too. After the age of 9-10 years the orthodontic treatment continued on the
      permanent teeth. If necessary, the sequelae on maxilla, lips and nose are treated
      at the end of the adolescence.

PMID- 12064206
TI  - [Management of cleft lip and palate by the Doctor Magalon's team in Marseille].
AB  - The goal of the treatment of patients with cleft lip and/or cleft palate was:
      obtain a normal appearance, a normal speech and a normal growth without severe
      pertubations of the quality of life. Millard technique was used to repair the
      cleft lip in neonatal period. Between 6 and 18 months, the palate cleft was
      closed by wardill-kilner technique. A gingivoperiostoplasty with osseous graft
      was performed between 8 and 12 years. The orthodontic treatment began at 7 years.
      Pharyngoplasty was necessary in several cases. Sequellae and rhinoplasty was
      performed at the end of the growth. The authors explained their choices.

PMID- 12064207
TI  - [Synthesis of the standard of treatment of cleft lip and cleft palate by 11
      francophone teams en 2001].
AB  - Influenced by Eurocleft project, the authors proposed a synthesis of the protocol
      of treatment for cleft palate and/or cleft lip patient by 11 french and belgian
      teams. If the goal are similar (restored anatomy with good appearance, good
      speech, normal hearing, facial growth and dental arch correct, good social
      integration) the methods to obtain this outcome are different in each cleft unit.
      Consensual points and dissensions were described in the discussion.

PMID- 12064208
TI  - [Information cards and enlightened assent. Proposition of twelve informant cards
      for plastic and aesthetic surgery].
AB  - Obligation to deliver full information and obtaining enlightened assent are now,
      for the whole french practitioner, a necessary preliminary to each operation.
      Henceforth, in case of suit, the practitioner must prove the reality and the
      quality of preoperative information. The National Medical French Council (CNOM)
      called scientific societies attention to propose to their members some index
      standard cards, corresponding to main medical and surgical records. The National
      Agency for Accreditation and Evaluation in Health (Anaes) defined the main
      characteristics of these documents. The authors propose twelve information cards
      corresponding to the most currently operations of plastic and aesthetic surgery.
      They will being clear and simple, with a large agreement, strictly informative
      and yearly up to date. They have the label and therefore the scientific guaranty
      of French Society of Plastic Reconstructive and Aesthetic Surgery.

PMID- 12064209
TI  - [Cleft lip and palate: retrospective study of 35 years of management].
AB  - The author having treated more than 2,000 C.L. (P) cases, and recognized his
      errors, delivers his main conclusions: 1--The Cupid-s bow always complete on the
      healthy side is to be strictly respected; 2--The nasal floor muscles should be
      identified and set in due place, especially the oblique part of the orbicularis
      oris, responsible for the nasal equilibrium; 3--The long muscular loop
      (orbicularis, buccinator, superior pharyngii constrictor) should be closed within
      the neo-natal period; 4--The velum should be closed and set back before the ninth
      month; in order to minimize scarring, only mucosal flaps should be taken from the
      palatal shelves; 5--If the velum deserves lengthening, tissue transfer by
      superiorly based pharyngeal flap, to be cut six months later; 6--Leave alone the
      bone until 7 or 8 years of age, close the gap with a Campbell flap; 7--Consider
      that no forceful orthopaedics can overwhelm the strength of scars developed over
      and between the palatal shelves. So, be light and late on the bone; 8--No
      addiction to any skin design provided some sort of Z-plasty is used; 9--Think
      muscle. Spare the bone.

PMID- 12064210
TI  - [The whole treatment of cleft lip and/or palate by the team of Dr. Chancholle in
      Toulouse].
AB  - Our choice in the treatment of the C.L.P. child is that the child is accepted by
      his parents and by Society as well as possible. In this way, the most important
      points are: to inform parents and Society of the ability of the child to a normal
      and satisfactory life. This information must be based upon the exact knowledge of
      what is really the cleft disease, its causes, and not only the genetic ones, the
      whole troubles induced by the cleft, local and general, and their treatment: by
      neonatal operation and, however was the choice of operative technic, by educative
      and reeducative means based on an exact knowledge of the modified physiology of
      the child: above all, sensory-motricity coordination and early speech-therapy
      before speech. The follow-up of the child at the difficult time of school
      admission, and cooperation between all the members of the team and the teachers.

PMID- 12064211
TI  - [Profession: internist...].

PMID- 12064212
TI  - [Legionnaires'disease: more unresolved questions].

PMID- 12064213
TI  - [Wilson's disease. Clinical presentation, treatment and evolution in 21 cases].
AB  - PURPOSE: Wilson's disease is characterized by neuropsychiatric symptoms with
      frequent extrapyramidal and intellectual presentations. They have an insidious
      evolution that leads to a late diagnosis and less therapeutic effectiveness in
      the advanced forms. METHODS: We report 21 cases of Wilson's disease with
      neurological complications, emphasizing clinical semiology, diagnostic means and
      problems of the therapeutics in our country. RESULTS: The average age at the
      beginning of the disease was 17.6 years, with a female prevalence (8/13). The
      signs at first were mostly all neurological (71.4%), then psychiatric (19%) or
      hepatic (19%). The most common neurological signs were dystonia of members (81%),
      dysarthria (76%), tremors (76%) or disorders of motoricity (71.4%). Sometimes
      there were sialorrhea or disorders of the handwriting. The Kayser-Fleischer ring
      was present in 19 patients. Eighteen patients had clinical and/or biological
      hepatic involvement. The diagnosis was confirmed by biochemical examinations,
      which found a low rate of copper in blood, a sinking rate of ceruloplasmin and a
      very high rate of urinary copper. The cerebral computer tomography shows a
      cortical and/or subcortical atrophy (37%), and/or a low density of the central
      grey cores (35%). The treatment was based on D-penicillamine and/or zinc sulfate,
      according to the availability of the drugs. The evolution was favourable among 18
      patients (85%) and not good in 42.8% of the cases. Six of the first patients had
      poor evolution after many years of follow-up. Finally, only 12 patients (57%) had
      a very good outcome. The family investigation made among 17 patients revealed 13
      family cases. The only predictive factor of a poor evolution was the therapeutic
      noncompliance (P = 0.006). CONCLUSIONS: The neurological presentations are
      traditional during the Wilson's disease, but are often ignored. We must suspect
      the disease in children when faced with disorders of handwriting or school
      failures and in the adult, when faced with neurological symptoms in a patient
      having a hepatic disease. We must not hesitate to consider it even given purely
      psychiatric signs, and we had better know to seek the neurological ones.

PMID- 12064214
TI  - [Value of the protein profile in the diagnosis of infectious endocarditis when
      hemolysis is present].
AB  - PURPOSE: Haptoglobin (H) and orosomucoid (O) are acute phase proteins that
      increase in a parallel manner. When hemolysis and inflammation are both present,
      study of the O-H couple on the protein profile may reveal an unknown hemolysis.
      METHODS: To determine if hemolysis is more frequent during infectious
      endocarditis than during septicemia without valvulopathy or during valvulopathy
      without septicemia. Study of three groups of patients: 26 patients with
      infectious endocarditis, 13 patients with septicemia and 36 patients with
      valvulopathy without septicemia. Studied parameters were the O-H couple,
      hemoglobin and rate of O. RESULTS: Hemolysis is clear in patients with
      endocarditis. The difference O-H is significantly more important during
      endocarditis than during septicemia without valvulopathy (P < 0.001) and during
      valvulopathy without sepsis (P < 0.001). CONCLUSION: Study of the O-H couple may
      be useful for the diagnosis of endocarditis showing a difficult-to-diagnose
      hemolysis.

PMID- 12064215
TI  - [DHEA: an unknown star].
AB  - PURPOSE: To clarify the physiological function of dehydroepiandrosterone (DHEA),
      the most abundant steroid in human plasma, which remains poorly understood. To
      analyse the beneficial effects of a supplementation in order to alleviate its
      decrease in ageing and improve well-being. CURRENT KNOWLEDGE AND KEY POINTS: DHEA
      (and its sulfate) acts on peripheral tissues as an androgenic and estrogenic
      precursor. It is also considered as a neurosteroid. DHEA administration in
      several pathological animal models is promising, especially in metabolic diseases
      such as obesity and insulin resistance. It appears like a factor of
      immunomodulation and facilitates cognitive acquisition. In humans there is little
      evidence that DHEA may be useful in characterized pathologies apart from adrenal
      insufficiency. An interesting effect was also noted in severe systemic lupus
      erythematosus. The effects on cognitive and neuropsychiatric diseases such as
      midlife dysthymia are not yet convincing. Prospective studies of supplementation
      versus placebo indicate inconstant improvement in well-being in the post
      menopausal state. DHEA is not a panacea against ageing despite there being a well
      established aging-related decrease of DHEA. Contrary to some assertions there are
      no proven relations between cardiovascular or cancer risk. FUTURE PROSPECTS AND
      PROJECTS: Until now adrenal insufficiency has been the only well-documented
      indication of an oral DHEA supplementation. However, DHEA may be a good way for
      androgen supplementation in menopausal men. Further investigations are needed to
      better know the anti-inflammatory and immunomodulation properties of DHEA. At the
      least, prospective studies on large populations are necessary to assess the true
      benefits and dangers of DHEA in prevention of ageing.

PMID- 12064216
TI  - [Hypoglycemia associated with pleural fibromas. Study of insulin-like growth
      factors (IGF) and pathogenic considerations].
AB  - PURPOSE: Pathogeny of hypoglycemia associated with non-islet-cell tumors is
      unclear. We discuss the mechanisms of this syndrome. CURRENT KNOWLEDGE AND KEY
      POINTS: We report three cases of spontaneous hypoglycemia revealing pleural
      fibroma. Endocrine tests before surgery showed low serum growth hormone and
      insulin-like growth factor I (IGF-I), reduced serum IGF-II levels in two patient.
      Insulin-like growth factor binding protein-3 (IGFBP-3) was low and
      electrophoretic profile of IGF-II was the 'big IGF-II' type. We discuss the
      mechanisms of hypoglycemia associated with non-islet-cell tumor. Impaired
      formation of the ternary complexes and its consequences seem the main pathogenic
      factor. FUTURE PROSPECTS AND PROJECTS: Analysis of IGF and IGFBP and in situ
      measurements of IGF mRNA could help in understanding this syndrome and allow
      therapeutic considerations in the management of hypoglycemia by corticosteroids
      and growth hormone.

PMID- 12064217
TI  - [Hip arthroplasty in genetic hemochromatosis. Report of 5 cases].
AB  - INTRODUCTION: Half of the patients with genetic hemochromatosis will have
      arthritis. Two of these articular involvements are well-known: the arthropathy
      involving the phalangeal and the metacarpophalangeal joints of the hand, useful
      for diagnosis, and hip arthropathy. Iron deposits seem to be involved in
      articular cartilage destruction. EXEGESIS: We report five cases of patients with
      hemochromatosis hip involvement. Hip arthropathy revealed hemochromatosis in one
      case and appeared despite efficient phlebotomies in another case. Three of these
      patients required hip arthroplasty. CONCLUSION: Hip arthropathy remains a
      frequent but unknown event in genetic hemochromatosis (12.5%) and it involves the
      functional prognosis.

PMID- 12064218
TI  - [Necrobiotic xanthogranuloma , a cutaneous disorder associated with monoclonal
      gammopathy].
AB  - INTRODUCTION: Necrobiotic xanthogranuloma is a rare cutaneous disorder usually
      associated with monoclonal gammapathy. We describe two new cases. EXEGESIS: A 70
      year-old patient was affected by a monoclonal gammopathy. She presented with a
      diplopia related to a retro-orbital tumor. The biopsy showed inflammatory
      lesions. Five years later, inflammatory xanthomatous skin lesions appeared.
      Biopsy specimens gave the diagnosis of necrobiotic xanthogranuloma. A 70-year-old
      woman was referred for inflammatory cutaneous lesions. Clinical, biological
      investigations and skin biopsies led to the diagnosis of cutaneous sarcoidosis
      associated with monoclonal gammopathy. Four years later, she developed a
      nephrotic syndrome. New skin biopsy specimens showed a necrobiotic
      xanthogranuloma. CONCLUSION: Necrobiotic xanthogranuloma is a systemic disease.
      It is a rare non-Langerhans cell histiocytosis characterized by frequent
      cutaneous and ophthalmologic lesions and associated with monoclonal gammopathy.
      To our knowledge, retro-orbital involvement has never been reported in
      necrobiotic xanthogranuloma. Treatment is difficult.

PMID- 12064219
TI  - [Pseudotumoral enterocolic phlebitis of the cecum and rutoside. A case report].
AB  - INTRODUCTION: Enterocolic phlebitis is an entity characterized by ischemic injury
      of the gastrointestinal tract caused by thrombophlebitis of the mesenteric veins
      without arterial involvement or systemic disease. EXEGESIS: We report a case of
      enterocolic phlebitis in a 57-year-old female treated by rutoside, revealed by
      intestinal obstruction related to a pseudotumoral lesion of the caecum.
      CONCLUSION: This case adds to the four cases of enterocolic phlebitis under
      rutoside already reported in the literature, suggesting a possible involvement of
      this drug in this rare disease.

PMID- 12064220
TI  - [Cerebral hemorrhage due to a ruptured mycotic aneurysm. Two cases].
AB  - INTRODUCTION: Cerebral hemorrhages due to rupture of mycotic aneurysms are rare
      but severe complications of infective endocarditis. We report two cases with a
      good outcome. EXEGESIS: The first patient presented with a parieto-occipital
      hematoma which occurred in the course of a relapsing infective endocarditis due
      to Streptococcus mitis. She fully recovered after neurosurgical treatment. In the
      second case, a right frontal hematoma revealed two mycotic aneurysms and an
      infective endocarditis due to Streptococcus gordonii. Motor weakness partially
      recovered after antibiotic therapy and angiography demonstrated complete
      resolution of aneurysms. CONCLUSION: Ruptured mycotic aneurysms are poor
      prognosis factors in infective endocarditis. Adapted antibiotic therapy is the
      first-intent treatment. Neurosurgery is indicated when hematomas are poorly
      tolerated and in cases requiring anticoagulant therapy.

PMID- 12064221
TI  - [A bad cae of pyoderma gangrenosum].

PMID- 12064222
TI  - [Chronic arthritis of the elbow caused by sarcoidosis].

PMID- 12064223
TI  - [Candida meningitis after a liver puncture biopsy].

PMID- 12064224
TI  - [Plexopathy associated with systemic scleroderma].

PMID- 12064225
TI  - [Tolosa-Hunt syndrome: result of effective imagery].

PMID- 12064226
TI  - Biogeography and floral evolution of baobabs (Adansonia, Bombacaceae) as inferred
      from multiple data sets.
AB  - The phylogeny of baobab trees was analyzed using four data sets: chloroplast DNA
      restriction sites, sequences of the chloroplast rpl16 intron, sequences of the
      internal transcribed spacer (ITS) region of nuclear ribosomal DNA, and
      morphology. We sampled each of the eight species of Adansonia plus three outgroup
      taxa from tribe Adansonieae. These data were analyzed singly and in combination
      using parsimony. ITS and morphology provided the greatest resolution and were
      largely concordant. The two chloroplast data sets showed concordance with one
      another but showed significant conflict with ITS and morphology. A possible
      explanation for the conflict is genealogical discordance within the Malagasy
      Longitubae, perhaps due to introgression events. A maximum-likelihood analysis of
      branching times shows that the dispersal between Africa and Australia occurred
      well after the fragmentation of Gondwana and therefore involved overwater
      dispersal. The phylogeny does not permit unambiguous reconstruction of floral
      evolution but suggests the plausible hypothesis that hawkmoth pollination was
      ancestral in Adansonia and that there were two parallel switches to pollination
      by mammals in the genus.

PMID- 12064227
TI  - Genetic distances and ordination: the land snail Helix aspersa in north Africa as
      a test case.
AB  - We examined the efficiencies of ordination methods in the treatment of gene
      frequency data at intraspecific level, using metric and nonmetric distance
      measures (Nei's and Rogers' genetic distances, chi 2 distance). We assessed
      initial processes responsible for the geographical distribution of the
      Mediterranean land snail Helix aspersa. Seventeen enzyme loci from 30 North
      African snail populations were considered in the present analysis. Five
      combinations of distance/multivariate analysis were compared: correspondence
      analysis (CA), nonmetric multidimensional scaling (NMDS) on Nei's, Rogers', and
      chi 2 distances, and principal coordinates analysis on Rogers' distances.
      Configuration of the objects resulting from ordination was projected onto three
      dimensional graphics with the minimum spanning tree or the relative neighborhood
      graph superimposed. Pre- and postordination or clustering distance matrices were
      compared by means of correlation methods. As expected, all combinations led to a
      clear west versus east pattern of variation. However, the intraregional
      relationships and degree of connectivity between pairs of operational taxonomic
      units were not necessarily constant from one method to another. Ordination
      methods when applied with Nei's and Rogers' distances provided the best fit, with
      original distances (r = 0.98) compared with UPGMA clustering (r approximately
      0.75). The Nei/NMDS combination seems to be a good compromise (distortion index
      dt = 10%) between Rogers/NMDS, which produces a more confusing pattern of
      differentiation (dt = 24%), and chi 2/CA, which tends to distort large distances
      (dt = 31%). NMDS obviously provides a powerful method to summarize relationships
      between populations, when neither hierarchical structure nor phylogenetic
      inference are required. These findings led the discussion on the good performance
      of NMDS, the appropriate distances to be used, and the potential application of
      this method to other types of allelic data (such as microsatellite loci) or data
      on nucleotide sequences of genes.

PMID- 12064228
TI  - Phylogenetic analysis and intraspecific variation: performance of parsimony,
      likelihood, and distance methods.
AB  - Intraspecific variation is abundant in all types of systematic characters but is
      rarely addressed in simulation studies of phylogenetic method performance. We
      compared the accuracy of 15 phylogenetic methods using simulations to (1)
      determine the most accurate method(s) for analyzing polymorphic data (under
      simplified conditions) and (2) test if generalizations about the performance of
      phylogenetic methods based on previous simulations of fixed (nonpolymorphic)
      characters are robust to a very different evolutionary model that explicitly
      includes intraspecific variation. Simulated data sets consisted of allele
      frequencies that evolved by genetic drift. The phylogenetic methods included
      eight parsimony coding methods, continuous maximum likelihood, and three distance
      methods (UPGMA, neighbor joining, and Fitch-Margoliash) applied to two genetic
      distance measures (Nei's and the modified Cavalli-Sforza and Edwards chord
      distance). Two sets of simulations were performed. The first examined the effects
      of different branch lengths, sample sizes (individuals sampled per species),
      numbers of characters, and numbers of alleles per locus in the eight-taxon case.
      The second examined more extensively the effects of branch length in the four
      taxon, two-allele case. Overall, the most accurate methods were likelihood, the
      additive distance methods (neighbor joining and Fitch-Margoliash), and the
      frequency parsimony method. Despite the use of a very different evolutionary
      model in the present article, many of the results are similar to those from
      simulations of fixed characters. Similarities include the presence of the
      "Felsenstein zone," where methods often fail, which suggests that long-branch
      attraction may occur among closely related species through genetic drift.
      Differences between the results of fixed and polymorphic data simulations include
      the following: (1) UPGMA is as accurate or more accurate than nonfrequency
      parsimony methods across nearly all combinations of branch lengths, and (2)
      likelihood and the additive distance methods are not positively misled under any
      combination of branch lengths tested (even when the assumptions of the methods
      are violated and few characters are sampled). We found that sample size is an
      important determinant of accuracy and affects the relative success of methods
      (i.e., distance and likelihood methods outperform parsimony at small sample
      sizes). Attempts to generalize about the behavior of phylogenetic methods should
      consider the extreme examples offered by fixed-mutation models of DNA sequence
      data and genetic-drift models of allele frequencies.

PMID- 12064229
TI  - Data decisiveness, data quality, and incongruence in phylogenetic analysis: an
      example from the monocotyledons using mitochondrial atp A sequences.
AB  - We examined three parallel data sets with respect to qualities relevant to
      phylogenetic analysis of 20 exemplar monocotyledons and related dicotyledons. The
      three data sets represent restriction-site variation in the inverted repeat
      region of the chloroplast genome, and nucleotide sequence variation in the
      chloroplast-encoded gene rbcL and in the mitochondrion-encoded gene atpA, the
      latter of which encodes the alpha-subunit of mitochondrial ATP synthase. The
      plant mitochondrial genome has been little used in plant systematics, in part
      because nucleotide sequence evolution in enzyme-encoding genes of this genome is
      relatively slow. The three data sets were examined in separate and combined
      analyses, with a focus on patterns of congruence, homoplasy, and data
      decisiveness. Data decisiveness (described by P. Goloboff) is a measure of
      robustness of support for most parsimonious trees by a data set in terms of the
      degree to which those trees are shorter than the average length of all possible
      trees. Because indecisive data sets require relatively fewer additional steps
      than decisive ones to be optimized on nonparsimonious trees, they will have a
      lesser tendency to be incongruent with other data sets. One consequence of this
      relationship between decisiveness and character incongruence is that if
      incongruence is used as a criterion of noncombinability, decisive data sets,
      which provide robust support for relationships, are more likely to be assessed as
      noncombinable with other data sets than are indecisive data sets, which provide
      weak support for relationships. For the sampling of taxa in this study, the atpA
      data set has about half as many cladistically informative nucleotides as the rbcL
      data set per site examined, and is less homoplastic and more decisive. The rbcL
      data set, which is the least decisive of the three, exhibits the lowest levels of
      character incongruence. Whatever the molecular evolutionary cause of this
      phenomenon, it seems likely that the poorer performance of rbcL than atpA, in
      terms of data decisiveness, is due to both its higher overall level of homoplasy
      and the fact that it is performing especially poorly at nonsynonymous sites.

PMID- 12064230
TI  - Phylogeny of frogs of the Physalaemus pustulosus species group, with an
      examination of data incongruence.
AB  - Characters derived from advertisement calls, morphology, allozymes, and the
      sequences of the small subunit of the mitochondrial ribosomal gene (12S) and the
      cytochrome oxidase I (COI) mitochondrial gene were used to estimate the phylogeny
      of frogs of the Physalaemus pustulosus group (Leptodactylidae). The combinability
      of these data partitions was assessed in several ways: measures of phylogenetic
      signal, character support for trees, congruence of tree topologies, compatibility
      of data partitions with suboptimal trees, and homogeneity of data partitions.
      Combined parsimony analysis of all data equally weighted yielded the same tree as
      the 12S partition analyzed under parsimony and maximum likelihood. The COI,
      allozyme, and morphology partitions were generally congruent and compatible with
      the tree derived from combined data. The call data were significantly different
      from all other partitions, whether considered in terms of tree topology alone,
      partition homogeneity, or compatibility of data with trees derived from other
      partitions. The lack of effect of the call data on the topology of the combined
      tree is probably due to the small number of call characters. The general
      incongruence of the call data with other data partitions is consistent with the
      idea that the advertisement calls of this group of frogs are under strong sexual
      selection.

PMID- 12064231
TI  - Influence of alignment on the mtDNA phylogeny of Cetacea: questionable support
      for a Mysticeti/Physeteroidea clade.

PMID- 12064232
TI  - On the best evolutionary rate for phylogenetic analysis.
AB  - The effect of the evolutionary rate of a gene on the accuracy of phylogeny
      reconstruction was examined by computer stimulation. The evolutionary rate is
      measured by the tree length, that is, the expected total number of nucleotide
      substitutions per site on the phylogeny. DNA sequence data were simulated using
      both fixed trees with specified branch lengths and random trees with branch
      lengths generated from a model of cladogenesis. The parsimony and likelihood
      methods were used for phylogeny reconstruction, and the proportion of correctly
      recovered branch partitions by each method was estimated. Phylogenetic methods
      including parsimony appear quite tolerant of multiple substitutions at the same
      site. The optimum levels of sequence divergence were even higher than upper
      limits previously suggested for saturation of substitutions, indicating that the
      problem of saturation may have been exaggerated. Instead, the lack of information
      at low levels of divergence should be seriously considered in evaluation of a
      gene's phylogenetic utility, especially when the gene sequence is short. The
      performance of parsimony, relative to that of likelihood, does not necessarily
      decrease with the increase of the evolutionary rate.

PMID- 12064233
TI  - Long-branch distraction and the Strepsiptera.

PMID- 12064235
TI  - On applications of geometric morphometrics to studies of ontogeny and phylogeny.

PMID- 12064234
TI  - Lagomorphs misplaced by more characters and fewer taxa.

PMID- 12064236
TI  - Partial warps, phylogeny, and ontogeny: a comment on Fink and Zelditch (1995).

PMID- 12064238
TI  - Taxonomic sampling, phylogenetic accuracy, and investigator bias.

PMID- 12064237
TI  - Sensitivity of phylogeny estimation to taxonomic sampling.
AB  - Recent studies have shown that addition or deletion of taxa from a data matrix
      can change the estimate of phylogeny. I used 29 data sets from the literature to
      examine the effect of taxon sampling on phylogeny estimation within data sets. I
      then used multiple regression to assess the effect of number of taxa, number of
      characters, homoplasy, strength of support, and tree symmetry on the sensitivity
      of data sets to taxonomic sampling. Sensitivity to sampling was measured by
      mapping characters from a matrix of culled taxa onto optimal trees for that
      reduced matrix and onto the pruned optimal tree for the entire matrix, then
      comparing the length of the reduced tree to the length of the pruned complete
      tree. Within-data-set patterns can be described by a second-order equation
      relating fraction of taxa sampled to sensitivity to sampling. Multiple regression
      analyses found number of taxa to be a significant predictor of sensitivity to
      sampling; retention index, number of informative characters, total support index,
      and tree symmetry were nonsignificant predictors. I derived a predictive
      regression equation relating fraction of taxa sampled and number of taxa
      potentially sampled to sensitivity to taxonomic sampling and calculated values
      for this equation within the bounds of the variables examined. The length
      difference between the complete tree and a subsampled tree was generally small
      (average difference of 0-2.9 steps), indicating that subsampling taxa is probably
      not an important problem for most phylogenetic analyses using up to 20 taxa.

PMID- 12064239
TI  - Inferring complex phylogenies using parsimony: an empirical approach using three
      large DNA data sets for angiosperms.
AB  - To explore the feasibility of parsimony analysis for large data sets, we
      conducted heuristic parsimony searches and bootstrap analyses on separate and
      combined DNA data sets for 190 angiosperms and three outgroups. Separate data
      sets of 18S rDNA (1,855 bp), rbcL (1,428 bp), and atpB (1,450 bp) sequences were
      combined into a single matrix 4,733 bp in length. Analyses of the combined data
      set show great improvements in computer run times compared to those of the
      separate data sets and of the data sets combined in pairs. Six searches of the
      18S rDNA + rbcL + atpB data set were conducted; in all cases TBR branch swapping
      was completed, generally within a few days. In contrast, TBR branch swapping was
      not completed for any of the three separate data sets, or for the pairwise
      combined data sets. These results illustrate that it is possible to conduct a
      thorough search of tree space with large data sets, given sufficient signal. In
      this case, and probably most others, sufficient signal for a large number of taxa
      can only be obtained by combining data sets. The combined data sets also have
      higher internal support for clades than the separate data sets, and more clades
      receive bootstrap support of > or = 50% in the combined analysis than in analyses
      of the separate data sets. These data suggest that one solution to the
      computational and analytical dilemmas posed by large data sets is the addition of
      nucleotides, as well as taxa.

PMID- 12064240
TI  - Large-scale phylogenies and measuring the performance of phylogenetic estimators.
AB  - Performance measures of phylogenetic estimation methods such as accuracy,
      consistency, and power are an attempt at summarizing an ensemble of a given
      estimator's behavior. These summaries characterize an ensemble behavior with a
      single number, leading to a variety of definitions. In particular, the
      relationships between different performance measures such as accuracy and
      consistency or accuracy and error depend on the exact definition of these
      measures. In addition, it is relatively common to use large-sample behavior to
      infer similar behavior for small samples. In fact, large-sample results such as
      the claimed asymptotic efficiency of the maximum-likelihood estimator are often
      uninformative for small samples. Conversely, small-sample behavior using
      simulations is sometimes used to imply large-sample behavior such as consistency.
      However, such extrapolation is often difficult. How the performance of a
      phylogenetic estimator scales with the addition of taxa must be qualified with
      respect to whether the whole tree is being estimated or a fixed subset of taxa is
      being estimated. It must also be qualified with respect to how tree models are
      sampled. Over the ensemble of all possible trees of a given size, the performance
      of the estimators for the whole tree estimate suffers when the tree size becomes
      larger. However, under certain models of cladogenesis, the estimate can improve
      with the addition of taxa. In fact, at all numbers of taxa there are subsets of
      tree models that are easier to estimate than others. This suggests that with
      judicious addition or subtraction of taxa we can move from tree models that are
      more difficult to estimate at one number of taxa to those that are easier to
      estimate at another number of taxa.

PMID- 12064241
TI  - Amphioxus mitochondrial DNA, chordate phylogeny, and the limits of inference
      based on comparisons of sequences.
AB  - Analyses of both the nucleotide and amino acid sequences derived from all 13
      mitochondrial protein-encoding genes (12,234 bp) of 19 metazoan species,
      including that of the lancelet Branchiostoma floridae ("amphioxus"), fail to
      yield the widely accepted phylogeny for chordates and, within chordates, for
      vertebrates. Given the breadth and the compelling nature of the data supporting
      that phylogeny, relationships supported by the mitochondrial sequence comparisons
      are almost certainly incorrect, despite their being supported by equally weighted
      parsimony, distance, and maximum-likelihood analyses. The incorrect groupings
      probably result in part from convergent base-compositional similarities among
      some of the taxa, similarities that are strong enough to overwhelm the historical
      signal. Comparisons among very distantly related taxa are likely to be
      particularly susceptible to such artifacts, because the historical signal is
      already greatly attenuated. Empirical results underscore the need for approaches
      to phylogenetic inference that go beyond simple site-by-site comparison of
      aligned sequences. This study and others indicate that, once a sequence sample of
      reasonable size has been obtained, accurate phylogenetic estimation may be better
      served by incorporating knowledge of molecular structures and processes into
      inference models and by seeking additional higher order characters embedded in
      those sequences, than by gathering ever larger sequence samples from the same
      organisms in he hope that the historical signal will eventually prevail.

PMID- 12064242
TI  - A fast method for approximating maximum likelihoods of phylogenetic trees from
      nucleotide sequences.
AB  - We have developed a rapid parsimony method for reconstructing ancestral
      nucleotide states that allows calculation of initial branch lengths that are good
      approximations to optimal maximum-likelihood estimates under several commonly
      used substitution models. Use of these approximate branch lengths (rather than
      fixed arbitrary values) as starting points significantly reduces the time
      required for iteration to a solution that maximizes the likelihood of a tree.
      These branch lengths are close enough to the optimal values that they can be used
      without further iteration to calculate approximate maximum-likelihood scores that
      are very close to the "exact" scores found by iteration. Several strategies are
      described for using these approximate scores to substantially reduce times needed
      for maximum-likelihood tree searches.

PMID- 12064243
TI  - Is it better to add taxa or characters to a difficult phylogenetic problem?
AB  - The effects on phylogenetic accuracy of adding characters and/or taxa were
      explored using data generated by computer simulation. The conditions of this
      study were constrained but allowed for systematic investigation of certain
      parameters. The starting point for the study was a four-taxon tree in the
      "Felsenstein zone," representing a difficult phylogenetic problem with an extreme
      situation of long branch attraction. Taxa were added sequentially to this tree in
      a manner specifically designed to break up the long branches, and for each tree
      data matrices of different sizes were simulated. Phylogenetic trees were
      reconstructed from these data using the criteria of parsimony and maximum
      likelihood. Phylogenetic accuracy was measured in three ways: (1) proportion of
      trees that are completely correct, (2) proportion of correctly reconstructed
      branches in all trees, and (3) proportion of trees in which the original four
      taxon statement is correctly reconstructed. Accuracy improved dramatically with
      the addition of taxa and much more slowly with the addition of characters. If
      taxa can be added to break up long branches, it is much more preferable to add
      taxa than characters.

PMID- 12064244
TI  - Morphology, molecules, and the phylogenetics of cetaceans.
AB  - Recent phylogenetic analyses of cetacean relationships based on DNA sequence data
      have challenged the traditional view that baleen whales (Mysticeti) and toothed
      whales (Odontoceti) are each monophyletic, arguing instead that baleen whales are
      the sister group of the odontocete family Physeteridae (sperm whales). We
      reexamined this issue in light of a morphological data set composed of 207
      characters and molecular data sets of published 12S, 16S, and cytochrome b
      mitochondrial DNA sequences. We reach four primary conclusions: (1) Our
      morphological data set strongly supports the traditional view of odontocete
      monophyly; (2) the unrooted molecular and morphological trees are very similar,
      and most of the conflict results from alternative rooting positions; (3) the
      rooting position of the molecular tree is sensitive to choice of artiodactyls
      outgroup taxa and the treatment of two small but ambiguously aligned regions of
      the 12S and 16S sequences, whereas the morphological root is strongly supported;
      and (4) combined analyses of the morphological and molecular data provide a well
      supported phylogenetic estimate consistent with that based on the morphological
      data alone (and the traditional view of toothed-whale monophyly) but with
      increased bootstrap support at nearly every node of the tree.

PMID- 12064245
TI  - Marijuana. A medical need.

PMID- 12064246
TI  - My illnesses are so big and I feel so small.

PMID- 12064248
TI  - An open letter of concern. Jailed activists: war-time terrorism standards now
      threaten non-violent direct action on AIDS.

PMID- 12064247
TI  - In these times. Liberty on the defensive.

PMID- 12064249
TI  - Hand surgery in Japan.

PMID- 12064250
TI  - Infection control: preventing iatrogenic transmission of spongiform
      encephalopathy in Danish hospitals.
AB  - The Danish infection control guidelines dealing with transmissible spongiform
      encephalopathy (TSE) recognise that preventive measures to avoid iatrogenic
      transmission must be taken, though the risk for patients in Danish hospitals can
      be characterised as minimal. A minimal risk situation cannot meanwhile be
      maintained unless hospitals and other healthcare institutions are prepared and
      have effective and well-functioning decontamination procedures in place suited
      for the purpose. The guidelines recommend that staff both in the operating
      theatre and in the Central Sterile Supply Department (CSSD) must be able to apply
      the procedures needed for safe handling and decontamination of used instruments.
      These include cleaning and effective sterilisation, as well as quarantine
      procedures and ways to discard and incinerate certain used instruments. The
      guidelines also address occupational safety, and single-use instruments are
      recommended where these are available and can be safely used. Effective
      procedures for decontamination of instruments and other medical devices are
      identified as the key to prevention of iatrogenic spread of TSE. Hospitals are
      advised to have their sterilisers and other equipment professionally checked in
      order to make sure that specific procedures for safe handling and decontamination
      of used surgical instruments and other medical equipment are available in case of
      suspected or confirmed TSE.

PMID- 12064251
TI  - Prion diseases: epidemiology in man.
AB  - Prion disease in man was first described as Creutzfeldt-Jacob disease (CJD) in
      the 1920s. CJD may have three different origins: sporadic, familial, due to
      mutations in the prion gene, or infectious, due to iatrogenic exposure to
      infectious brain material. As an example of the latter, kuru, in Papua New
      Guinea, was a variant of CJD transmitted by cannibalism. Between 1957 and 1982
      more than 2500 died of kuru. Sporadic CJD is the most common form of CJD and
      occurs with an incidence of around one per million in most parts of the world.
      Familial CJD accounts for approximately 10% of all European cases of CJD, and is
      associated with inherited mutations of the prion protein gene, caused by one of
      the 24 single amino acid substitutions or insertions of octapeptide repeats. CJD
      caused by infections involves either iatrogenic cases of CJD, resulting from
      exposure to infectious brain, pituitary or ocular tissue, or from ingestion of
      infected food items. As of today, a few hundred iatrogenic cases of CJD have been
      diagnosed worldwide, the majority due to transmission by cadaveric pituitary HCG.
      So far, 111 cases of vCJD have been diagnosed caused by BSE-contaminated food.
      The size of the epidemic is still unclear and worst-case scenarios indicate that
      we may expect many thousands of cases in the future.

PMID- 12064252
TI  - Early and late pathogenesis of natural scrapie infection in sheep.
AB  - The pathogenesis of scrapie infection was studied in sheep carrying the
      PrP(VRQ)/PrP(VRQ) genotype, which is associated with a high susceptibility for
      natural scrapie. The sheep were killed at sequential time points during a scrapie
      infection covering both the early and late stages of scrapie pathogenesis.
      Various lymphoid and neural tissues were collected and immunohistochemically
      examined for the presence of the scrapie-associated prion protein PrP(Sc), a
      marker for scrapie infectivity The first stage of scrapie infection consisted of
      invasion of the palatine tonsil and Peyer's patches of the caudal jejunum and
      ileum, the so-called gut-associated lymphoid tissues (GALT). At the same time,
      PrP(Sc) was detected in the medial retropharyngeal lymph nodes draining the
      palatine tonsil and the mesenteric lymph nodes draining the jejunal and ileal
      Peyer's patches. From these initial sites of scrapie replication, the scrapie
      agent disseminated to other non-GALT-related lymphoid tissues. Neuroinvasion
      started in the enteric nervous system followed by retrograde spread of the
      scrapie agent via efferent parasympathetic and sympathetic nerve fibres
      innervating the gut, to the dorsal motor nucleus of the vagus in the medulla
      oblongata and the intermediolateral column of the thoracic spinal cord segments
      T8-T10, respectively.

PMID- 12064253
TI  - Prion diseases. An overview.
AB  - Prion disease is the new designation of a group of spongiform encephalopathies,
      all invariably fatal, which show similar clinical and neuropathological changes.
      They comprise a range of distinct diseases in both animals and man, and
      spontaneous, hereditary and transmissible forms are recognized. Until the sudden
      occurrence in the mid-1980s of an epizootic of a formerly unknown disease,
      popularly named 'mad cow disease', in cattle in the UK, very little attention had
      been paid to these rather obscure diseases. Concurrently it was asserted that the
      disease-causing agent appeared to be a ubiquitous mammalian brain constituent,
      and the disease mechanism a conformational change of its structure. These events
      have not only led to a new understanding of these extraordinary diseases, but
      have also provided insight into both neurodegeneration and disease mechanisms at
      the molecular level. Moreover, in 1997 the prion concept earned its originator
      the second Nobel price for medicine within this scientific field. In this
      introduction and overview of prion diseases, historical and philosophical
      perspectives are presented along with descriptions of the diseases in both
      animals and man. Epidemiology, genetics and transmissibility are also covered.

PMID- 12064255
TI  - Species-barrier-independent prion replication in apparently resistant species.
AB  - Prion diseases of humans and animals are associated with the accumulation of an
      abnormal isoform (PrP(Sc)) of the host-encoded prion protein (PrP(C)).
      Transmission of these diseases between mammalian species is usually limited by a
      'species barrier', which can be mediated by differences in primary sequence of
      the prion protein between donor and host species. Studies on species barriers
      usually rely on the development of clinical disease in inoculated animals as an
      assessment of susceptibility in a particular host. Recent studies by a number of
      groups have demonstrated that the absence of clinical symptoms does not
      necessarily exclude transmission of prion disease across a species barrier. Such
      results indicate that subclinical or carrier states exist in these diseases,
      which has public health implications regarding human exposure to BSE prions and
      iatrogenic transmission from apparently healthy humans. Here the issue of
      subclinical prion diseases is reviewed and implications are discussed.

PMID- 12064254
TI  - Influence of the prion protein gene, Prnp, on scrapie susceptibility in sheep.
AB  - Natural scrapie in sheep occurs through a complex interplay between host genetic
      elements and various strains of the infectious scrapie agent. Scrapie-related
      polymorphisms in the coding region of the prion protein (PrP) gene, Prnp, have
      been studied in a number of breeds. The disease-promoting V136 allele, and the
      susceptibility-reducing R171 allele, have proved to be most important. However,
      variation in the coding region of Prnp cannot alone explain the diverse patterns
      of scrapie susceptibility in various breeds. For instance, in many breeds plagued
      with scrapie, the V136 allele appears to be a rarity. The R171 allele greatly
      reduces scrapie susceptibility This lays the molecular foundation for marker
      assisted breeding for reduced scrapie susceptibility now underway in many
      countries. Although potentially important, and still under investigation,
      variable expression level and pattern of the ovine Prnp appears to be of little
      importance for the occurrence of natural scrapie. Studies of scrapie in mice also
      indicate that genetic elements other than Prnp may have a strong influence on
      scrapie incubation time, and hence susceptibility. Narrowing down the search to
      focus on these elements and identification of candidate genes are important tasks
      for future research in sheep scrapie.

PMID- 12064256
TI  - Survey of laboratory findings in suspected cases of bovine spongiform
      encephalopathy in Denmark from 1990 to 2000.
AB  - A survey of the laboratory findings in suspected cases of bovine spongiform
      encephalopathy (BSE) in Denmark from 1 June 1990 to 31 December 2000 is
      presented. During this period BSE was a notifiable disease, and the heads of
      suspected cases were submitted according to the legislation on BSE. A total of
      176 submissions were made, mostly from bovines with neurological disorders and
      mainly during the last 3 years of this period. Lesions or other laboratory
      findings consistent with severe neurological disorders were found in 115 cases.
      The most frequent diagnosis was encephalic listeriosis (35.8% of submissions)
      followed by other forms of inflammatory lesions. A wide range of lesions were
      diagnosed less prevalent. BSE was diagnosed twice. The first case occurred in an
      imported cow in 1992, while the second confirmed case was diagnosed in a native
      cow in February 2000. A marked increase in the number of submissions occurred
      following the detection of BSE in February 2000.

PMID- 12064257
TI  - Monitoring and analysis of bovine spongiform encephalopathy (BSE) testing in
      Denmark using statistical models.
AB  - The evolution of monitoring and surveillance for bovine spongiform encephalopathy
      (BSE) from the phase of passive surveillance that began in the United Kingdom in
      1988 until the present is described. Currently, surveillance for BSE in Europe
      consists of mass testing of cattle slaughtered for human consumption and cattle
      from certain groups considered to be at higher risk of having clinical or
      detectable BSE. The results of the ongoing BSE testing in Denmark have been
      analyzed using two statistical approaches: the "classical" frequentist and the
      Bayesian that is widely used in quantitative risk analysis. The analyses were
      intended to provide information for decision-makers, the media and the public as
      well as to provide inputs for future BSE surveillance models. The results to date
      suggest that the total number of BSE cases that will be found in Denmark in 2001
      will not exceed 16.

PMID- 12064258
TI  - Transmission of prion disease.
AB  - The transmission of bovine spongiform encephalopathy to humans as variant
      Creutzfeldt-Jakob disease (vCJD) has focused public attention on how prion
      diseases are transmitted and how prions reach the brain after exposure. Prion
      diseases are characterised by transmissibility and neuropathological features of
      gliosis, neuronal loss and microscopic vacuoles, termed spongiosis. The principal
      component of prions is the glycoprotein PrP(Sc), which is a conformational
      modified isoform of the normal membrane protein PrP(C). How are prions
      transmitted and how do prions find their way once they have been ingested? Prion
      models in mouse and hamster point to lymphoreticular cells which support an early
      replication phase of prions before reaching the central nervous system via
      peripheral nerves. Whilst some key players seem to have been identified so far,
      the mechanisms of prion propagation to the brain are still not fully understood.
      Seemingly contradictory results have led to some confusion and have provoked
      discussion.

PMID- 12064259
TI  - Pathological diagnosis of variant Creutzfeldt-Jakob disease.
AB  - The neuropathological and biochemical features of the 89 histologically confirmed
      cases of variant Creutzfeldt-Jakob disease (vCJD) diagnosed up to the end of
      October 2001 in the UK are reviewed. Histology of the central nervous system,
      lymphoid tissues and other organs was accompanied by immunocytochemistry and
      Western blot analysis of the disease-associated form of the prion protein
      (PrP(RES)). All patients with vCJD were methionine homozygotes at codon 129 of
      the PrP gene. The pathology of vCJD showed relatively uniform morphological and
      immunocytochemical characteristics, which were distinct from other forms of CJD.
      PrP(RES) accumulation was widespread in lymphoid tissues in vCJD, but was not
      identified in other non-neural tissues. PrP(RES) in vCJD brain tissue showed a
      uniform glycotype pattern distinct from sporadic CJD. Given the increasingly
      widespread occurrence of bovine spongiform encephalopathy in Europe and Asia,
      there is a major need for widespread CJD surveillance. This should be accompanied
      by a multidisciplinary laboratory approach to the investigation and diagnosis of
      all forms of CJD, with the need to investigate autopsy tissues from suspected
      cases by the histological and biochemical techniques described herein.

PMID- 12064260
TI  - Clinical diagnosis and differential diagnosis of CJD and vCJD. With special
      emphasis on laboratory tests.
AB  - The most widely distributed form of transmissible spongiform encephalopathy,
      sporadic Creutzfeldt-Jakob disease, typically affects patients in their sixties.
      Rapidly progressive dementia is usually followed by focal neurological signs and
      typically myoclonus. The disease duration in sporadic CJD is shorter than in
      variant CJD (6 months and 14 months, respectively). The clinical diagnosis in
      sporadic CJD is supported by the detection of periodic sharp and slow wave
      complexes in the electroencephalogram, hyperintense signals in basal ganglia on
      magnetic resonance imaging and elevated levels of neuronal proteins in the
      cerebrospinal fluid (such as 14-3-3). In contrast to the sporadic form,
      hyperintense signals in the posterior thalamus ("pulvinar sign") are seen in
      variant CJD. Following recent developments in diagnostic premortem techniques,
      clinical criteria for probable sporadic and probable variant CJD were
      established. Clinicopathological studies on sporadic CJD revealed different
      phenotypes which are characterized by neuropathological lesion profile, clinical
      syndrome, codon 129 genotype and type of proteinase K-resistant core of the prion
      protein. Alzheimer's disease and Lewy body dementia are the most frequent
      differential diagnoses in sporadic CJD in elderly patients, whereas chronic
      inflammatory disorders of the central nervous system have to be considered in
      younger patients.

PMID- 12064261
TI  - Blood infectivity in transmissible spongiform encephalopathies.
AB  - Blood infectivity in transmissible spongiform encephalopathies (TSE) is reviewed
      with special emphasis on transmission by blood transfusion in human beings. It is
      concluded that transmission by transfusion seems biologically plausible as
      regards variant Creutzfeld-Jakob Disease (vCJD), albeit present knowledge
      suggests that it is extremely uncommon. Precautionary measures against the
      putative risk of vCJD transmission by blood transfusion are discussed.

PMID- 12064262
TI  - Mixing fire & EMS successfully in Kenner, LA.

PMID- 12064263
TI  - The man in the wooden box.

PMID- 12064264
TI  - September 11: a personal account.

PMID- 12064265
TI  - How everything works.

PMID- 12064266
TI  - Marital status, cohabitation, and risk of preterm birth in Europe: where births
      outside marriage are common and uncommon.
AB  - This article explores whether the impact of marital status on the risk of preterm
      birth varies in relation to marital practices in the population, defined by the
      proportion of out-of-marriage births. Data come from a case-control study of the
      determinants of preterm birth in 16 European countries (5456 cases and 8234
      controls). There is a significantly elevated risk of preterm birth associated
      with both cohabitation (OR = 1.29 [1.08, 1.55]) and single motherhood (OR = 1.61
      [1.26, 2.07]) for women living in countries where fewer than 20 of births occur
      outside marriage. In contrast, there is no excess risk associated with marital
      status when out-of-marriage births are more common. This overall result does not
      apply to all subgroups of preterm births: different patterns emerge for early
      preterm births and preterm births induced for medical reasons. It is important to
      consider social context in the analysis of individual risk factors.

PMID- 12064267
TI  - The increase in very-low-birthweight infants in Germany: artefact or reality?
AB  - Earlier findings have shown that after unification with the Federal Republic of
      Germany (FRG) in October 1990 the proportion of very-low-birthweight infants in
      the former German Democratic Republic (GDR) increased. This study seeks to
      explore this observation in more detail at the regional level. The analysis of
      aggregate data of live births in Germany between 1991 and 1997 shows an
      increasing proportion of very-low-birthweight infants as well as a general trend
      towards heavier babies in both east and west. The growing proportion of live born
      infants at very low birthweights in the east, however, seems to be due, in part,
      to increased registration, most likely reflecting the introduction of the more
      comprehensive (western) definition of a live birth with unification in October
      1990. A fairly distinct east-west pattern in the birthweight distribution present
      in 1991 had almost disappeared by 1997 and given way to a north-south one.

PMID- 12064268
TI  - Preterm birth, stillbirth and infant mortality among triplet births in Canada,
      1985-96.
AB  - Recent increases in the frequency of multiple births and simultaneous increases
      in preterm birth among multiple births have focused attention on such births.
      However, most previous studies have examined twins rather than higher-order
      multiples. We carried out a study to examine rates and trends in preterm birth
      and in gestational age-specific fetal and infant mortality among triplet births
      in Canada. We used data from the stillbirth, live birth and mortality files of
      Statistics Canada for the years 1985-97. All births in Canada (excluding those
      occurring in Ontario and Newfoundland) were included in the study, with two
      periods (1985-90 vs. 1991-96) being contrasted for assessing temporal change.
      Changes were estimated using relative risks, 95 confidence intervals [CI] and two
      tailed P-values. The rate of preterm birth among triplet live births increased by
      6 (95 CI 3, 9) from 90.4 in 1985-90 to 96.0 in 1991-96. Stillbirth rates among
      triplets did not change significantly and were 30.3 per 1000 total births in 1985
      90 and 33.8 per 1000 total births in 1991-96. Infant mortality among triplets
      declined from 112.7 per 1000 live births in 1985-90 to 73.8 per 1000 live births
      in 1991-96. In spite of temporal reductions in infant mortality, triplet births
      continue to be associated with very high rates of preterm birth and fetal and
      infant mortality. Fetal mortality among triplets has not changed over the last
      ten years.

PMID- 12064269
TI  - Maternal age, anthropometrics and pregnancy oestriol.
AB  - It has been hypothesised that oestrogen exposure in utero influences the risk for
      breast cancer in adult life. Although several studies report associations between
      breast cancer and maternal factors associated with birthweight of the offspring -
      a marker for antenatal oestriol exposure - little is known about the relations
      between maternal oestrogen levels and these factors per se. We therefore analysed
      the association between oestriol levels in 188 women in the 17th, 25th, 33rd and
      37th weeks of pregnancy, and maternal age, prepregnancy weight, height and
      pregnancy weight gain. Both maternal prepregnancy body mass index and maternal
      height were, after controlling for infant birthweight, independently and
      inversely associated with oestriol levels (P = 0.0021 and P = 0.0006
      respectively). We found no association between maternal age or pregnancy weight
      gain and pregnancy oestriol levels. These findings suggest that the previously
      reported associations between maternal age and maternal pregnancy weight gain and
      the offsprings risk of breast cancer are due to factors other than antenatal
      exposure to oestriol.

PMID- 12064270
TI  - Malnutrition and susceptibility to enteroparasites: reinfection rates after mass
      chemotherapy.
AB  - The evidence that relates malnutrition to enteroparasite infections arises from
      studies that demonstrate the improvement of nutritional indicators after
      antiparasitism treatment. However, the role of malnutrition as an aggravating
      factor to the susceptibility to enteroparasite infections is still not fully
      understood. We investigated the correlation between malnutrition and
      enteroparasite infection after mass chemotherapy, in a poor city of Sao Paulo
      State, Brazil. The sample comprised 759 children between 1 and 10 years of age of
      whom 585 were followed up for a period of 1 year and periodically assessed for
      reinfection with enteroparasites. One year of follow-up after mass chemotherapy
      demonstrated that 38 of the undernourished children were reinfected with
      enteroparasites, as compared with 25 of the eutrophic children (P = 0.033). The
      survival multivariate analysis demonstrated that, after controlling for the
      potential confounding variables, maternal literacy and per capita income rate,
      malnutrition was associated with susceptibility to reinfection (P = 0.13). We
      demonstrate that, although maternal literacy and per capita income rate are
      indeed confounding variables, malnutrition contributes to an increase in the risk
      of enteroparasite infections.

PMID- 12064271
TI  - Implications of cleaning gestational age data.
AB  - Gestational age is an important birth characteristic examined in epidemiological
      studies. Though there are well-documented problems with the reporting of
      gestational age on birth certificates, schemes for addressing this issue have not
      been systematically evaluated. With singleton births from the 1995-97 US linked
      birth/infant death files, we compared a handful of perinatal outcome estimates
      derived from the resulting analytical files using two published methods often
      used to manage inconsistent gestational age data. The first method (Alexander et
      al., 1996), provides cut-points for implausible birthweight-gestational age
      combinations and excludes infants with birthweights outside a plausible range.
      The second (Zhang and Bowes, 1995), provides different cut-points for implausible
      birthweight-gestational age combinations and then substitutes the clinical
      gestational age estimate for the original value, if available, reducing the
      number of births at the affected gestational age, but excluding fewer births from
      the resulting analytical files. The Alexander method excluded 0.4 of our study
      population and the Zhang method reassigned and excluded 1.0 and 0.2,
      respectively; however, over 20 of birth records with gestational age 28-30 weeks
      were modified by either method. Using either method, more high-risk than low-risk
      and more black than white births were excluded. These differential exclusions
      affected corresponding perinatal outcome estimates and relative risks between
      maternal risk groups for preterm delivery, gestation-specific infant mortality
      and birthweight; overall infant mortality rates were not affected. Systematic
      comparisons between results of different studies will need to consider the data
      modifications used, the populations affected, and the outcomes assessed when
      drawing conclusions.

PMID- 12064272
TI  - HIV test kits could be in short supply.

PMID- 12064273
TI  - AIDS undermines international education, says World Bank.

PMID- 12064274
TI  - More arrests made in South Dakota for HIV exposure.

PMID- 12064275
TI  - ACLU sues Louisiana officials over abstinence education.

PMID- 12064276
TI  - CDC suggests annual HIV tests for gay, bisexual men.

PMID- 12064277
TI  - Coinfection. Researchers recommend routine HIV testing for TB patients.

PMID- 12064279
TI  - Developing countries could miss genomics research benefits.

PMID- 12064278
TI  - Minorities. Study finds racial disparities in HIV/AIDS clinical trials.

PMID- 12064280
TI  - International Red Cross, Red Crescent fight AIDS stigma.

PMID- 12064281
TI  - Lawmakers urged to continue focus on domestic AIDS epidemic.

PMID- 12064282
TI  - U.S. blocks reproductive health rights in U.N. declaration.

PMID- 12064283
TI  - UNAIDS urges more effort to fight AIDS among children.

PMID- 12064284
TI  - HIV/AIDS a global economic threat, UN official warns.

PMID- 12064286
TI  - Child sexual abuse treatment: misinterpretation and mismanagement of child sexual
      behavior.
AB  - OBJECTIVE: The purpose of the study was to examine caregiver understanding of the
      impact of child sexual abuse and the management of abused children in residential
      treatment. METHODS: A purposive sample of 20 registered nurses and child care
      workers were interviewed about their experiences working in residential treatment
      and their knowledge about child development and child sexual abuse and its
      application to practice. Data from interviews and field notes were analysed using
      dimensional analysis. FINDINGS: Caregivers had limited knowledge of the sequelae
      of child sexual abuse. Developmentally appropriate behaviour of sexually abused
      children, as well as behavioural manifestations of child sexual abuse, were often
      misinterpreted and mismanaged. CONCLUSION: Residential care of sexually abused
      children should be based on sound developmental principles and caregiver
      sensitivity.

PMID- 12064285
TI  - Reduced activation of inflammatory responses in host cells by mouse-adapted
      Helicobacter pylory isolates.
AB  - Helicobacter pylori strains that harbour the Cag pathogenicity island (Cag PAI)
      induce interleukin (IL)-8 secretion in gastric epithelial cells, via the
      activation of NF- kappa B, and are associated with severe inflammation in humans.
      To investigate the influence of Cag PAI-mediated inflammatory responses on H.
      pylori adaptation to mice, a selection of H. pylori clinical isolates (n = 12)
      was cag PAI genotyped and tested in co-culture assays with AGS gastric epithelial
      cells, and in mouse colonization studies. Six isolates were shown to harbour a
      complete cag PAI and to induce NF- kappa B activation and IL-8 secretion in AGS
      cells. Of the eight isolates that spontaneously colonized mice, six had a cag
      PAI(-) genotype and did not induce pro-inflammatory responses in these cells.
      Mouse-to-mouse passage of the two cag PAI(+) -colonizing strains yielded host
      adapted variants that infected mice with bacterial loads 100-fold higher than
      those of the respective parental strains (P= 0.001). These mouse-adapted variants
      were affected in their capacity to induce pro-inflammatory responses in host
      cells, yet no changes in cag PAI gene content were detected between the strains
      by DNA microarray analysis. This work provides evidence for in vivo selection of
      H. pylori bacteria with a reduced capacity to induce inflammatory responses and
      suggests that such bacteria are better adapted to colonize mice.

PMID- 12064287
TI  - Motor performance and behaviour in preterm and full-term 3-year-old children.
AB  - AIM: To compare the motor performance and behaviour at 3 years of age of very
      preterm, moderately preterm and full-term children (n = 221), who needed neonatal
      intensive care (NIC), and of 72 neonatally healthy full-term children (reference
      group). METHOD: A model for combined assessment of motor performance and
      behaviour (CAMPB) was used. The children's performance was assessed on the basis
      of observations and documentation of categories of co-ordination, attention and
      social behaviour included in CAMPB. RESULTS: Significantly more very preterm
      children showed deviations in co-ordination than children in the other groups,
      and this difference was most evident in comparison with the reference group. No
      differences were found between the groups regarding attention and social
      behaviour during the assessment. CONCLUSION: Very preterm children differ from
      moderately preterm and full-term children in their motor performance at 3 years
      of age. By means of CAMPB, individual children with pronounced incoordination
      were identified in all groups, and some of them also showed pronounced lack of
      attention.

PMID- 12064288
TI  - Child/parent-assessed population health outcome measures: a structured review.
AB  - AIMS: To identify generic measures of health-related quality of life (HRQL) for
      children and adolescents developed for use within general populations.
      Instruments are evaluated on the basis of evidence relating to their reliability
      and validity. METHODS: Systematic literature searches were used to identify
      instruments, which were then assessed against predefined criteria. Information
      relating to instrument content, population, reliability and validity was
      extracted from published papers. RESULTS: Sixteen instruments were identified
      that had been evaluated among a general population of children or adolescents.
      Four instruments had reported data on both internal consistency and test-retest
      reliability. All except two instruments had undergone some degree of construct
      validation. CONCLUSIONS: The evidence suggests that the Child Health
      Questionnaire (CHQ) has been the most extensively evaluated for younger
      populations but is available as a parent-completed measure only. The new version
      of the Child Health and Illness Profile (CHIP-CE) is particularly promising and
      has parallel child- and parent-completed versions for young ages. The weight of
      evidence suggests that versions of these two instruments are suitable for older
      children. The Warwick Child Health and Morbidity Profile could be used where
      information on morbidity and health service contacts is required. Once basic
      psychometric criteria are fulfilled, instruments should be chosen by assessing
      their content and design in the light of the prospective application.

PMID- 12064289
TI  - Assessing the quality of preschool child health surveillance in primary care: a
      pilot study in one health district.
AB  - OBJECTIVE: To develop a framework for measuring the quality of preschool child
      health surveillance acceptable to primary health care teams and measurable at
      individual primary health care team level. DESIGN: Published research evidence
      was identified and criteria developed by a local multidisciplinary expert group.
      The criteria were discussed with primary health care teams. How well they were
      achieved was assessed. SETTING: Twenty-eight general practices in one health
      authority area. METHODS: Data collection included observation of baby clinics,
      interviews with health visitors and general practitioners (GPs), questionnaires
      to parents, collation of child health surveillance reviews recorded in personal
      child health records and immunization rates. RESULTS: The criteria for assessing
      preschool child health surveillance were thought to be acceptable and achievable
      by primary health care teams. Fifteen of the 22 criteria used to assess baby
      clinics were met by over 90 of practices. Almost all practices completed child
      health surveillance reviews within a standard time and achieved 90 coverage for
      primary immunizations. At many practices, less than 90 of parents felt welcome at
      the baby clinic, usually had enough time to talk to their health visitor or had
      the purpose or results of the 6 to 8 week child health surveillance review
      explained to them. GPs were less likely than health visitors to discuss health
      promotion at child health surveillance reviews (chi(2) 11.52, P = 0.0007). Few
      practices had a call-up and recall system for all reviews. CONCLUSION: The
      framework that we developed for assessing preschool child health surveillance was
      acceptable and achievable by primary health care teams.

PMID- 12064290
TI  - Inhibition of cell proliferation and fibronectin biosynthesis by Na ascorbate.
AB  - BACKGROUND: The importance of ascorbate on the production of extracellular matrix
      proteins (as elastin and collagens) is now well documented, but no studies have
      been published concerning its effects on fibronectin biosynthesis. Fibronectin is
      important for cell attachment and for proliferation. MATERIALS AND METHODS: The
      effects of Na ascorbate were investigated on cell attachment, proliferation,
      viability and fibronectin biosynthesis by human skin fibroblasts in vitro.
      Proliferation was followed by the monitoring of [(3)H]-thymidine incorporation;
      viability by the MTT-test, cell adherence by counting adherent and nonadherent
      cells and fibronectin biosynthesis by immunoprecipitation of biosynthetically
      labelled fibronectin. RESULTS: In the presence of ascorbate, the fibroblasts
      showed a biphasic growth pattern. At 500 microM ascorbate, [(3)H]-thymidine
      incorporation was stimulated by 15% as compared to the controls. Higher
      concentrations gradually decreased proliferation up to 36% of the control value
      at 5 mM. These effects of ascorbate on DNA synthesis were followed to > 1.25 mM
      by a strong inhibition, cytotoxic effect and cell death. The non-adherent cell
      count increased to 10% of the total population at 2.5 mM and to 31% at 5.0 mM
      ascorbate.Increasing concentrations of ascorbate resulted in a dose-dependent
      decrease of fibronectin biosynthesis, both in the culture supernates and cell
      extracts. This inhibition mainly concerned cell membrane-associated
      fibronectin.Superoxide-dismutase or catalase could inhibit Na ascorbate-induced
      cytotoxicity and partially re-establish fibronectin biosynthesis.
      Desferrioxamine, ergothionein and vitamin E were inefficient. CONCLUSIONS: Our
      results indicate that ascorbate decreases fibronectin biosynthesis of cultured
      human skin fibroblasts, thereby producing cell detachment and decreased
      proliferation. This effect is mainly mediated by the reactive oxygen species and
      can be inhibited by superoxide-dismutase and catalase.

PMID- 12064291
TI  - Surfing for sex.

PMID- 12064292
TI  - E-risk?

PMID- 12064293
TI  - The Internet as a medium for HIV prevention and counseling.

PMID- 12064294
TI  - Living with HIV and hepatitis C.

PMID- 12064295
TI  - HIV and hepatitis C: the basics.

PMID- 12064296
TI  - HIV & hepatitis C: "co-infection".

PMID- 12064297
TI  - HIV and hepatitis C. Lab tests you should know about.

PMID- 12064299
TI  - Hepatitis C: pregnancy and children.

PMID- 12064298
TI  - HIV & hepatitis C: treatment.

PMID- 12064300
TI  - Hepatitis C resources.

PMID- 12064301
TI  - New-Fill to treat facial wasting.
AB  - Looking in the mirror can be a humbling experience. For HIV positive people with
      facial wasting, or lipoatropy, the experience can be traumatic. Facial lipoatropy
      refers to subcutaneous fat loss in the cheeks and temples resulting in a bony,
      emaciated appearance. The condition may mild to severe. As with other symptoms of
      lipodystrophy, or body fat abnormality syndrome (such as fat loss in the limbs
      and buttocks, and fat accumulation in the abdomen), the only thing known for
      certain about facial wasting is that it exists; precise causes have not been
      identified and successful strategies to prevent the condition remain elusive. A
      recently developed cosmetic treatment for facial wasting, polylactic acid (PLA)
      or New-Fill, appears to be well tolerated in European clinical trials and
      anecdotal reports. Although the treatment has been approved in Europe and Mexico,
      the future of PLA access in the U.S. remains uncertain.

PMID- 12064302
TI  - Global fundamentals.

PMID- 12064303
TI  - Microbicides to prevent heterosexual transmission of HIV: ten years down the
      road.
AB  - The development of topical microbicides for HIV prevention originated in response
      to the unabated spread of HIV despite the availability of an effective HIV
      prevention tool (condoms), as well as the lack of an effective HIV vaccine.
      Initially, hopes were pinned on existing over-the-counter spermicides containing
      nonoxynol-9. Concern about the toxicity of nonoxynol-9 with frequent use, and its
      small or nonexistent protective effect against HIV and other sexually transmitted
      infections (STIs), has spurred the development of new microbicides with a number
      of novel mechanisms of action. Significant progress has been made in the last
      decade. The microbicides pipeline currently contains approximately 34 products in
      preclinical development, 15 in Phase I safety trials, four in Phase II expanded
      safety and preliminary effectiveness trials, and three in Phase II/III or Phase
      III effectiveness trials. Laboratory and clinical research has been complemented
      by a growing body of research and literature on microbicide acceptability, harm
      reduction and dual protection strategies, and potential markets. However, many
      challenges remain, including the need for a significant increase in investment to
      accelerate product development and complementary research, and to plan for
      availability and access once effective microbicides are available.

PMID- 12064304
TI  - Managing nausea, vomiting, and diarrhea.

PMID- 12064305
TI  - Science, money, and industry: is commerce corrupting AIDS research?

PMID- 12064306
TI  - No acceptable excuse for inaction.

PMID- 12064307
TI  - TAC, MSF import generic AIDS drugs into South Africa.

PMID- 12064308
TI  - New antiretroviral tactics, new antiretrovirals, old side effects. 41st
      Interscience Conference on Antimicrobial Agents and Chemotherapy.

PMID- 12064309
TI  - IV International Congress on Peer Review in Biomedical Publication. Barcelona,
      Spain, September 14-16, 2001.

PMID- 12064310
TI  - JAMA patient page. Medical journals.

PMID- 12064311
TI  - Highlights from the 3rd International Workshop on Clinical Pharmacology of HIV
      Therapy.

PMID- 12064313
TI  - Invirase vs. Fortovase: unexpected results?

PMID- 12064312
TI  - Saquinavir with low-dose ritonavir twice daily.

PMID- 12064314
TI  - Saquinavir once daily.

PMID- 12064316
TI  - Could cimetidine be used as a booster?

PMID- 12064315
TI  - Teaching adherence to substance users.

PMID- 12064317
TI  - Delavirdine in rescue regimens.

PMID- 12064318
TI  - Drugs and the liver updated, 2002.

PMID- 12064319
TI  - Nursing homes need cash very urgently.

PMID- 12064320
TI  - Any nurse can be a health facilitator.

PMID- 12064321
TI  - JAMA patient page. Temporal arteritis.

PMID- 12064322
TI  - Reader suggests fuller appreciation of findings.

PMID- 12064323
TI  - Cultural dimensions of anxiety and truth telling.

PMID- 12064324
TI  - A multifocal education strategy to enhance hospital-based Cultural competency in
      professional staff.

PMID- 12064325
TI  - Self-care for fatigue in patients With HIV.
AB  - PURPOSE/OBJECTIVES: To identify when fatigue is reported as a problem by people
      who are HIV positive, what the perception of fatigue is, and which self-care
      behaviors are used and with what efficacy. DESIGN: Multisite descriptive study.
      SETTING: University-based AIDS clinics, community-based organizations, and
      homecare agencies located in cities across the United States, in Norway, and
      through a university Web site. SAMPLE: Convenience sample of 422 self-identified
      people who are HIV positive. MAIN RESEARCH VARIABLES: Symptom description,
      symptom relief, symptom help, and self-care strategies. FINDINGS: The sixth most
      reported symptom in this study, fatigue, was treated with a variety of self
      designed strategies. In only three instances was consultation with a healthcare
      provider (i.e., physician) or an injection (medication not defined) mentioned.
      The most frequently used interventions were supplements, vitamins, and nutrition
      followed by sleep and rest; exercise; adjusting activities, approaches, and
      thoughts; distraction; and complementary and alternative therapies. In addition
      to self-designed strategies, the media and friends and family were sources of
      information. CONCLUSIONS: Fatigue was reported less frequently in this study than
      in other HIV-, AIDS-, or cancer-related studies. This may be an artifact of the
      study design. The use of informal networks for assistance, let alone the
      prevalence of unrelieved fatigue, indicates the need for more attention to this
      problem among people with AIDS. IMPLICATIONS FOR NURSING: Careful assessment of
      the pattern of fatigue and its onset, duration, intervention, and resolution is
      required if the varied types of fatigue are to be identified and treated
      successfully.

PMID- 12064326
TI  - Risk-adjusted analysis of surgeon performance: a 1-year study.

PMID- 12064327
TI  - N-3 fatty acids and lipid peroxidation in breast cancer inhibition.
AB  - Long-chain n-3 fatty acids (FA) consistently inhibit the growth of human breast
      cancer (BC) cells both in culture and in grafts in immunosuppressed mice. Large
      cohort studies have, however, failed to confirm a protective effect for fish oils
      rich in n-3 FA against BC risk. The present review examines new evidence on
      biological mechanisms which may be involved in the inhibition of mammary
      carcinogenesis by long-chain n-3 FA, focusing on an apoptotic effect by its lipid
      peroxidation products. Dietary intake of n-3 FA leads to their incorporation into
      cell membrane lipids. Increased apoptosis in human BC cells following exposure to
      long-chain n-3 FA such as eicosapentaenoic and docosahexaenoic acids is generally
      ascribed to their inhibition of cyclooxygenase 2 which promotes mammary
      carcinogenesis. In addition however, long-chain n-3 FA are particularly likely to
      activate peroxisome proliferator-activated receptor (PPAR)-gamma, a key regulator
      of lipid metabolism but also capable of modulating proliferative activity in a
      variety of cells including mammary cells. Expression of PPAR-gamma in the nucleus
      is activated by second messengers such as J series prostaglandins and the latter
      have been shown to cause apoptosis in vivo in explants of human BC cells in
      immunosuppressed mice. In mammary tumours, it is observed that long-chain FA not
      only increase apoptosis, but also increase lipid peroxidation, and the apoptotic
      effect can be reversed by antioxidants. The rationale for use of n-3 FA dietary
      supplements in counteracting BC progression needs to be tested clinically in a
      phase 2 pilot study, while at the same time, the effect on whole-body lipid
      peroxidation needs to be monitored. Dietary supplements of fish oil rich in n-3
      FA are proposed for premenopausal women over the age of 40 years who are shown to
      be at increased BC risk. Biological markers in breast tissue of BC progression
      will be monitored, and observed changes related to serial plasma levels of
      isoprostanes as a measure of whole-body lipid peroxidation.

PMID- 12064328
TI  - Dietary myristic acid modifies the HDL-cholesterol concentration and liver
      scavenger receptor BI expression in the hamster.
AB  - The influence of myristic acid in a narrow physiological range (0.5 to 2.4% of
      total dietary energy) on the plasma and hepatic cholesterol metabolism was
      investigated in the hamster. The hamsters were fed on a diet containing 12.5 g
      fat/100 g and 0.05 g cholesterol/100 g with 0.5% myristic acid (LA diet) for 3
      weeks (pre-period). During the following 3 weeks (test period), they were divided
      into four dietary groups with 0.5% (LA), 1.2% (LM), 1.8% (ML) or 2.4% (M)
      myristic acid. Finally, half the hamsters in each group were again fed the LA
      diet for another 3 weeks (post-period). At the end of the test period, the
      hepatic expression of the scavenger receptor BI (SR-BI) was lower in the LM, ML
      and M groups than in the LA group whereas the hepatic cholesteryl ester
      concentration was higher. Cholesterol 7alpha hydroxylase activity was lower in
      the ML and M groups than in the LA and LM groups while the sterol 27 hydroxylase
      and 3-hydroxy-3-methyl glutaryl coenzyme A reductase activities were not
      modulated by dietary myristic acid. This is the first time a negative correlation
      has been observed between the HDL-cholesterol concentration and the hepatic mass
      of SR-BI (r -0.69; P<0.0001) under physiological conditions. An inverse linear
      regression was also shown between SR-BI and the percentage of myristic acid in
      the diet (r -0.75; P<0.0001). The hepatic mass of SR-BI in the M group had
      increased at the end of the post-period compared with the test-period values. The
      present investigation shows that myristic acid modulates HDL-cholesterol via a
      regulation of the SR-BI expression.

PMID- 12064329
TI  - Functional characterization of three clones of the human intestinal Caco-2 cell
      line for dietary lipid processing.
AB  - We aimed to improve the use of the human intestinal Caco-2 cell line for studying
      dietary lipid and cholesterol processing by using isolated pure clones (Chantret
      et al. 1994). Three clones (TC7, PD7 and PF11) were grown as monolayers on semi
      permeable filters and compared for cell viability, fatty acid and cholesterol
      apical uptake or basolateral secretion, apolipoprotein B-48 basolateral secretion
      and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. The TC7 clone showed
      the best viability upon apical incubation with mixed micelles and should be
      preferred for routine work. Short-term (3.0 h) rates of apical uptake of
      cholesterol were not different with the three clones, whereas the rate of apical
      uptake of oleic acid (18:1) was lower (P<0.05) with PF11 (250.6 nmol/mg) and the
      basolateral secretion of cholesterol and oleic acid was lower with the TC7 clone
      (0.40 and 29.1 nmol/mg respectively). The secretion of apolipoprotein B-48
      basolaterally was about 2-fold lower than from PD7 clone. The basal levels of HMG
      CoA reductase activity were significantly different (P<0.05; TC7>PF11 >PD7). The
      down-regulation of the enzyme activity was moderate (range 13.8-21.0%) and
      comparable in the presence of apical micellar cholesterol, but was much marked
      upon basolateral incubation with LDL (range 34.0-53.6%), especially for the PD7
      clone. In conclusion, the Caco-2 clones characterized here proved to be
      particularly suitable for studying lipid nutrients processing. Because these
      three clones exhibit some different metabolic capabilities, they provide a new
      tool to study intestinal response to lipid nutrients.

PMID- 12064330
TI  - Menaquinone-4 in breast milk is derived from dietary phylloquinone.
AB  - The effect of maternal phylloquinone supplementation on vitamin K in breast milk
      was studied to establish: (1) if phylloquinone is the source of menaquinone-4 in
      breast milk; (2) the dose-effect relationship between intake and obtainable
      levels. Four groups of lactating mothers with a full-term healthy infant
      participated and took oral phylloquinone supplements of 0.0 (n 8), 0.8 (n 8), 2.0
      (n 8), and 4.0 (n 7) mg/d for 12d, starting at day 4 post-partum. Milk samples
      were collected on days 4, 8, 16, and 19. Blood samples were collected on days 4
      and 16. Vitamin K and vitamin E concentrations, the latter for reason of
      comparison, were assayed. Phylloquinone and menaquinone-4 were present in all
      milk samples: 5.84 (SD 2.31) and 2.98 (SD 1.51) nmol/l (n 31) respectively, in
      colostrum (day 4 sample). A strong correlation between the vitamers was found (r
      0.78, P<0.001). Breast-milk phylloquinone levels were raised in a dose-dependent
      manner: 4-, 12-, and 30-fold on day 16 for the 08, 2.0, and 4.0 mg group
      respectively. In addition, menaquinone-4 levels were higher: 2.5- (P<0.05) and 7
      fold (P<0.001) in the 2.0 and 4.0 mg groups respectively. Plasma of supplemented
      subjects contained 3-, 5-, and 10-fold higher phylloquinone levels on day 16.
      Detectable menaquinone-4 was found in ten of thirty-one day 4 plasma samples. All
      day 16 plasma samples of the 4mg supplemented group contained the vitamin. There
      was no correlation between the K-vitamers in plasma. Vitamin E and phylloquinone
      appear to differ in their distribution in breast milk, milk:plasma concentration
      ratios were < or =1 and 3-5 for vitamin E and phylloquinone respectively. The
      milk:plasma concentration ratio of menaquinone-4 was >10. In conclusion, dietary
      phylloquinone is a source of menaquinone-4 in breast milk. Phylloquinone
      supplementation to lactating mothers may be of benefit to the newborn infant,
      since both phylloquinone and menaquinone-4 are raised by supplementation.

PMID- 12064331
TI  - Effect of esterified 4-desmethylsterols and -stanols or 4,4'-dimethylsterols on
      cholesterol and bile acid metabolism in hamsters.
AB  - 4-Desmethylsterols and -stanols reduce plasma total cholesterol (TC) and LDL
      cholesterol by inhibition of intestinal cholesterol absorption, while the
      cholesterol-lowering potential of 4,4'-dimethylsterols is less well defined. The
      present study aimed to compare the effects of 4-desmethylsterols, -stanols, and
      4,4'-dimethylsterols on plasma and hepatic cholesterol, sterol excretion and bile
      acid metabolism. Male golden Syrian hamsters were fed diets containing 13 g/100 g
      fat, 008 g/100 g cholesterol and 0 (control), 0.24 or 0.48% (w/w) esterified 4
      desmethylsterols (sterols) and esterified hydrogenated 4-desmethylsterols
      (stanols) from common vegetable oils or esterified 4,4'-dimethylsterols from rice
      bran oil for 5 weeks. Sterol and stanol esters at the dose of 0.24% were equally
      effective and significantly (P<0.05) lowered TC by 15%, while 0.24% 4,4
      dimethylsterols reduced TC by 10%. Liver total and esterified cholesterol
      concentrations were significantly (P<0.05) lowered by 40, 22, 43 and 31% in
      hamsters fed 0.48% sterols, 0.24% stanols, 0.48% stanols or 0.48%
      dimethylsterols, respectively. Daily faecal bile acid excretion and hepatic
      cholesterol 7alpha-hydroxylase activity were not altered, indicating that
      sterols, stanols and dimethylsterols had no effect on the intestinal re
      absorption of bile acids or on hepatic bile acid synthesis. Daily excretion of
      cholesterol was significantly higher in hamsters fed esterified sterols and
      stanols, but was only slightly increased in those fed dimethylsterols. The
      results indicate that esterified sterols and stanols were equally effective in
      lowering plasma TC and LDL cholesterol, while dimethylsterol esters caused a
      weaker cholesterol-lowering effect. Sterols and stanols achieve their cholesterol
      lowering effect by stimulating faecal cholesterol excretion through inhibiting
      intestinal cholesterol absorption, but do not affect bile acid excretion. Other
      mechanisms need to be considered to explain the effect on plasma and hepatic
      cholesterol of dimethylsterols.

PMID- 12064332
TI  - Effects of calcium and plant sterols on serum lipids in obese Zucker rats on a
      low-fat diet.
AB  - Ca may interfere with fat and cholesterol metabolism through formation of
      insoluble soaps with fatty and bile acids in the intestine. In the present study,
      we examined the effects of different dietary Ca levels on the serum lipid profile
      and cholesterol metabolism in obese Zucker rats fed a low-fat diet. We also
      tested whether dietary Ca interfered with the lipid-lowering effects of a pine
      oil-derived plant sterol mixture. Increase in dietary Ca intake from 0.2 to 0.8%,
      and further to 2.1% (w/w) dose-dependently decreased serum total cholesterol (r 
      0.565, P=0.002, n 27), LDL-cholesterol (r -0.538, P=0.006, n 25), and
      triacylglycerol (r -0.484, P=0.014, n 25) concentrations, and increased HDL
      cholesterol (r -0.478, P=0.016, n 25) and HDL: LDL cholesterol (r 0.672, P<0.001,
      n 25) in rats fed a 1% cholesterol diet. Analysis of serum campesterol:
      cholesterol and sitosterol: cholesterol suggested that Ca dose-dependently
      increased intestinal cholesterol absorption (r 0.913, P<0.001, n 18), whereas
      serum desmosterol: cholesterol and lathosterol: cholesterol indicated that Ca
      dose-dependently increased endogenous cholesterol synthesis (r 0.691, P=0.003, n
      18). Therefore, the decrease of serum LDL-cholesterol appeared to be due to Ca
      induced increase in the conversion of cholesterol to bile acids. The increase in
      Ca intake did not interfere with the beneficial effects of plant sterols on serum
      total cholesterol, LDL-cholesterol and HDL-cholesterol concentrations. The high
      Ca diet with plant sterol supplementation further increased the HDL-cholesterol
      concentration and HDL: LDL cholesterol. The present findings indicate that the
      beneficial effects of dietary Ca on the serum lipid profile during a low-fat diet
      are dose-dependent, and resemble those of bile acid sequestrants. Increased
      dietary Ca did not impede the lipid-lowering effects of natural plant sterols.

PMID- 12064333
TI  - The effect of maternal smoking and ethanol on fatty acid transport by the human
      placenta.
AB  - The role of the placenta in controlling the supply of fatty acids to the fetus
      was investigated in term placentas from non-smokers (n 5), smokers (>ten
      cigarettes/d; n 5) and after addition of ethanol at 2 mg/ml (n 4). The maternal
      side was of the placenta was perfused ex vivo for 90 min with a physiological
      mixture of fatty acids and fatty acid:human albumin ratio. There was no effect of
      smoking on the transfer of linoleic (LA, 18: 2 n-6), alpha-linolenic (alphaLN,
      18: 3 n-3), arachidonic (AA, 20: 4 n-6) or docosahexaenoic acid (DHA, 22: 6 n-3),
      expressed per perfused area (calculated from H2(18)O exchange). However, the
      presence of ethanol in the perfusate at a concentration of 2 mg/ml significantly
      reduced (P<0.01) the absolute rate of transfer of the two n-3 polyunsaturated
      fatty acids, alphaLN and DHA. This specific effect of ethanol on alphaLN and DHA
      also resulted in an altered selectivity for transfer of individual fatty acids.
      In the non-smoking control group the placenta selectively transferred
      polyunsaturated fatty acids to the fetus in the order DHA > AA > alphaLN > LA.
      The order of selectivity was unaltered in placentas from smokers, but the
      addition of ethanol to the perfusion medium altered the order of selectivity to
      AA > alphaLN > LA > DHA. The presence of ethanol in the perfusate was also
      associated with a significant reduction (P<0.05) in the clearance of H2(18)O.
      These results suggest that the presence of ethanol at a concentration of 2mg/ml
      may reduce the availability of polyunsaturated fatty acids to the developing
      fetus.

PMID- 12064334
TI  - Preferential incorporation of trans, trans-conjugated linoleic acid isomers into
      the liver of suckling rats.
AB  - The present study was designed to compare the conjugated linoleic acid (CLA)
      isomeric distribution pattern in the liver of suckling rats in relation to those
      in the milk and maternal diet. Silver-ion HPLC was used to separate individual
      CLA isomers. It was found that the isomeric distribution pattern in the milk was
      very similar to that in the maternal dietary fat. However, the CLA isomeric
      distribution patterns in the liver phospholipids (PL) and triacylglycerols were
      different from those in the diet and milk. In the liver PL, total cisltrans
      isomers accounted for 63.6-63.9% of total CLA, which was in contrast to the
      values of 88.1-89.1% in the milk and diet. In the liver PL, total transltrans
      isomers were 20.6-20.8% of the total CLA isomers whereas they were only 2.6-3.7%
      in the milk and diet. It is concluded that trans/trans-CLA were preferentially
      incorporated into the liver whereas for the incorporation of cis/trans-CLA there
      was partial discrimination.

PMID- 12064335
TI  - Induced changes in the consumption of coffee alter ad libitum dietary intake and
      physical activity level.
AB  - Dietary trials with subjects on a freely selected diet may be affected by
      unwanted behavioural changes. Few studies, if any, have examined changes in
      coffee consumption and possible concomitant changes in diet and health-related
      habits. The aim of the present study was to examine whether induced changes in
      coffee consumption lead to changes in food habits and leisure-time physical
      activity. Healthy, non-smoking coffee-drinkers (n 214) were asked to change their
      coffee habits in a controlled clinical trial on the metabolic effects of coffee.
      The participants were asked to maintain their usual dietary habits. Self
      perceived changes in diet and physical activity during the 6-week intervention
      period were assessed at the end. In the analyses, the participants were
      rearranged into groups reflecting the difference in coffee intake during the
      trial as compared with habitual intake. Associations with changes in food intake
      or physical activity were analysed by Spearman rank correlation. Changes in
      intake of 'chocolate, sweets' (r 0.179, P<0.05), 'cakes, sweet biscuits, pastry'
      (r 0.306, P<0.001), and 'jam' r 0.198, P<0.05) showed positive associations with
      change in coffee intake during the trial. Negative associations were found for
      'dishes with fish' (r -0.204, P<0.01) and many of the drinks as well as with
      physical activity (r -0.164, P<0.05). Induced changes in coffee intake seem to
      alter ad libitum intake of several foods. The recognized associations between
      health behaviours may have physiological explanations.

PMID- 12064336
TI  - Positive effects of a chicken eggshell powder-enriched vitamin-mineral supplement
      on femoral neck bone mineral density in healthy late post-menopausal Dutch women.
AB  - Although bone metabolism is largely under genetic control, the role of nutrition
      is considerable. The present study evaluates the effects of chicken eggshell
      powder, a new source of dietary Ca, and purified CaCO3 on bone mineral density
      (BMD) of the lumbar spine and hip. Besides BMD we also looked at biochemical
      markers of bone and Ca metabolism. Both Ca sources were provided in combination
      with minerals and vitamins including Mg, cholecalciferol and phylloquinone. We
      designed a randomised, double-blind, placebo-controlled study to take place over
      12 months. Healthy Caucasian women (n 85), selected by age (> or =50 and <70
      years), from the databases of general practitioners were recruited by telephone
      calls. They had to be at least 5 years post-menopausal, with lumbar spine T-score
      being > - 2.5. At baseline, their mean habitual daily Ca intake was adequate. The
      women were randomly allocated to: eggshell powder-enriched (group A; n 24),
      purified CaCO3-enriched (group B; n 22), or a placebo product (group C; n 27).
      BMD was measured at baseline and then after 6 and 12 months of supplementation as
      were the biochemical markers bone-specific alkaline phosphatase, amino-terminal
      propeptide extension of type I collagen, deoxypyridinoline, calcitonin, intact
      parathyroid hormone, calcidiol, and urinary Ca. After 12 months of
      supplementation, only mean BMD of the femoral neck in group A was significantly
      increased (P=0.014) by 1.75% (95% CI 0.18, 3.32) compared with a decrease of 
      0.60% (95% CI -1.92, 0.72) in group C. This increase coincided with significant
      decreases in markers of bone resorption and formation. No significant changes
      were seen in BMD at other sites, including lumbar spine, nor in groups B and C.
      No differences were found between groups A and B, or B and C. The present study
      indicates that healthy late post-menopausal women with an adequate Ca intake at
      baseline may increase BMD of the hip within 12 months following supplementation
      with the chicken eggshell powder-enriched supplement.

PMID- 12064337
TI  - Differential effects of n-3 and n-6 polyunsaturated fatty acids on BRCA1 and
      BRCA2 gene expression in breast cell lines.
AB  - Current evidence strongly supports a role for the breast tumour suppressor genes,
      BRCA1 and BRCA2, in both normal development and carcinogenesis. In vitro
      observations reported that BRCA1 and BRCA2 are expressed in a cell cycle
      dependent manner. Interestingly, differences in the actions of n-3 and n-6
      polyunsaturated fatty acids have been observed: while the n-3 polyunsaturated
      fatty acids have been described to reduce pathological cell growth, the n-6
      polyunsaturated fatty acids have been found to induce tumour proliferation. Here,
      we examined the expression of BRCA1 and BRCA2 in breast cell lines after
      treatment with polyunsaturated fatty acids. Real-time quantitative polymerase
      chain reaction determinations conclusively demonstrated increases in BRCA1 and
      BRCA2 mRNA expressions in MCF7 and MDA-MB 231 tumour cell lines after treatment
      with n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic
      acid), but no variation was noticed with the n-6 polyunsaturated fatty acid
      (arachidonic acid). On the other hand, no variation of the expression of BRCA1
      and BRCA2 mRNA was detected in MCF10a normal breast cell line treated by
      polyunsaturated fatty acids. The level of BRCA1 and BRCA2 proteins quantified by
      affinity chromatography remained unchanged in tumour (MCF7, MDA-MB 231) and
      normal (MCF10a) breast cell lines. We suggest the presence of a possible
      transcriptional or post-transcriptional regulation of BRCA1 and BRCA2 after n-3
      polyunsaturated fatty acid treatment in breast tumour cells.

PMID- 12064338
TI  - The comparative gastrointestinal response of young children to the ingestion of
      25 g sweets containing sucrose or isomalt.
AB  - Sugar-free confectionery products containing the low-energy, non-cariogenic
      sweetener isomalt are widely available in the market place and increasingly aimed
      at children. However, over-consumption of such products may lead to
      gastrointestinal symptoms and/or osmotic diarrhoea. Little is known about the
      gastrointestinal tolerance of children following consumption of isomalt. The aim
      of the present study was to assess gastrointestinal symptoms in children
      following consumption of sugar-free confectionery containing isomalt compared
      with sweets containing sucrose. In a double-blind, randomised, controlled,
      crossover study, sixty-seven children aged 6-9 years ingested 25 g hard-boiled
      sweets containing either sucrose or isomalt on two consecutive test days. Isomalt
      sweets were received as enthusiastically as sucrose sweets and, when given the
      choice, 97 % of children asked to be given the isomalt or the sucrose sweets on
      the second test day. Most children did not report multiple symptoms and few
      experienced symptoms on both days of isomalt consumption. However, significantly
      more children reported stomach-ache (P<0.01), abdominal rumbling (P<0.025) and
      passing watery faeces (P<0.001) following consumption of isomalt sweets compared
      with sucrose sweets. Consumption of 25 g isomalt-containing sweets by children is
      not associated with significant gastrointestinal effects graded as 'considerably
      more than usual' or multiple symptoms, but is associated with a laxative effect
      and increase in symptoms graded as 'slightly more than usual'. For the majority
      of children in the present study, 25 g isomalt-containing sweets represents an
      acceptable level of consumption, although some children are sensitive to the
      effects of isomalt ingestion.

PMID- 12064339
TI  - Procyanidins are not bioavailable in rats fed a single meal containing a
      grapeseed extract or the procyanidin dimer B3.
AB  - Flavanols are the most abundant flavonoids in the human diet where they exist as
      monomers, oligomers and polymers. In the present study, catechin, the procyanidin
      dimer B3 and a grape-seed extract containing catechin, epicatechin and a mixture
      of procyanidins were fed to rats in a single meal. After the meals, catechin and
      epicatechin were present in conjugated forms in both plasma and urine. In
      contrast, no procyanidins or conjugates were detected in the plasma or urine of
      any rats. Procyanidins were not cleaved into bioavailable monomers and had no
      significant effects on the plasma levels or urinary excretion of the monomers
      when supplied together in the grapeseed extract. We conclude that the nutritional
      effects of dietary procyanidins are unlikely to be due to procyanidins themselves
      or monomeric metabolites with the intact flavonoid-ring structure, as they do not
      exist at detectable concentrations in vivo. Future research should focus on other
      procyanidin metabolites such as phenolic acids and on the effects of the
      unabsorbed oligomers and polymers on the human gastrointestinal tract.

PMID- 12064340
TI  - Difference in the metabolism of vitamin K between liver and bone in vitamin K
      deficient rats.
AB  - The difference between vitamin K metabolism in the liver and that in the bone of
      vitamin K-deficient rats was examined. After 17 d administration of vitamin K
      deficient food, vitamin K in the liver was almost depleted, and prothrombin time
      (PT) was prolonged. Serum total osteocalcin level was slightly decreased by
      vitamin K deficiency, whereas serum undercarboxylated osteocalcin level did not
      change. The level of menaquinone (MK)-4 as well as that of phylloquinone was
      decreased, but approximately 40 % of the initial level still existed in the femur
      after the 17 d period. A single-dose administration of vitamin K (250 nmol/kg
      body weight) markedly increased vitamin K level in the liver but not in the
      femur. These results suggest that the turnover of vitamin K in the bone is slower
      than that in the liver, and bone metabolism may be little affected by the short
      period of intake of vitamin K-deficient food. However, intake of a larger amount
      of vitamin K is required for its accumulation in the bone than in the liver.
      Furthermore, the counteracting effect of MK-7 on prolonged PT in vitamin K
      deficient rats was found to be higher than phylloquinone or MK-4.

PMID- 12064341
TI  - The bioavailability and postprandial utilisation of sweet lupin (Lupinus albus)
      flour protein is similar to that of purified soyabean protein in human subjects:
      a study using intrinsically 15N-labelled proteins.
AB  - Sweet lupin (Lupinus albus), a protein-rich legume devoid of anti-nutritional
      factors, is considered to have a high potential for protein nutrition in man.
      Results concerning the nutritional value of lupin protein are, however,
      conflicting in animals and very scarce in human subjects. Furthermore, where
      fibre-rich protein sources are concerned, the long-term nutritional results are
      often obscured, particularly since fibre-promoted colonic fermentation may bias
      the energy supply and redistribute N flux. We therefore studied, during the
      postprandial phase, the bioavailability and utilisation of lupin-flour protein in
      nine healthy men who had ingested a mixed meal containing intrinsically 15N
      labelled lupin flour as the protein source (Expt 1). The real ileal digestibility
      (RID) and ileal endogenous N losses (IENL) were assessed using a perfusion
      technique at the terminal ileum, and the N content and 15N enrichment of ileal
      samples. Lupin flour exhibited a high RID of 91 (SD 3)% and low IENL (5-4 (SD
      1.3) mmol N/h). Postprandial dietary deamination was also assessed from body
      dietary urea and urinary dietary N excretion, and compared with results in nine
      healthy men following an iso-energetic meal containing a 15N-soyabean-protein
      isolate with a similar RID, as a control (Expt 2). Postprandial dietary
      deamination was similar after lupin and soyabean meals (17 (SD 2) and 18 (SD 4)%
      ingested N respectively). We therefore conclude that lupin protein is highly
      bioavailable, even if included in fibre-rich flour, and that it can be used with
      the same efficiency as soyabean protein to achieve postprandial protein gain in
      healthy human subjects.

PMID- 12064342
TI  - Digestibility and metabolic utilisation of dietary energy in adult sows:
      influence of addition and origin of dietary fibre.
AB  - According to a 4 x 4 Latin square design, four adult ovariectomised sows fed at a
      similar energy level (516 kJ ME/kg body weight (BW)0.75 per d) received one of
      four diets successively: a control low-dietary-fibre (DF) diet (diet C, 100 g
      total DF/kg DM) and three fibre-rich diets (200g total DF/kg DM) that
      corresponded to a combination of diet C and maize bran (diet MB), wheat bran
      (diet WB), or sugar-beet pulp (diet SBP). Sows were adapted to the diet for 12 d
      before an 8 d measurement period. Digestibility of energy and nutrients in the
      diets, and total heat production (HP) and its components (fasting HP, activity HP
      and thermic effect of feeding (TEF), were measured. The TEF was partitioned
      between a short-term component (TEF(st)) and a long-term component (TEF(lt)).
      Total tract digestibility of nutrients and energy was greater for diet C; among
      the three other diets, the digestibility coefficients were higher for diet SBP
      than for diets MB and WB. Energy losses from CH4 were linearly related to the
      digestible total DF intake (+1.4kJ/g). Fasting HP at zero activity averaged 260
      kJ/kg BW(0.75) per d. Activity HP represented 20% total HP, or 83 kJ/kg BW(0.75)
      per d on average. Total TEF and TEF(lt) were higher (P<0.05) for diet WB than for
      the other diets. However, total HP (406kJ/kg BW(0.75 per d) was not significantly
      affected by diet characteristics. Our results suggest that metabolic utilisation
      of dietary energy is little affected by the addition and origin of DF, at least
      under the conditions of the present study.

PMID- 12064343
TI  - Short-term consumption of a high-sucrose diet has a pro-oxidant effect in rats.
AB  - The underlying mechanisms for the detrimental consequences of a high-fructose
      diet in animal models are not clear. However, the possibility exists that
      fructose feeding facilitates oxidative damage. Thus, the aim of the present study
      was to assess, in weaning rats, the effect of a high-sucrose diet v. starch diet
      for 2 weeks on oxidative stress variables. Plasma lipid levels were measured and
      lipid peroxidation was evaluated by urine and plasma thiobarbituric acid-reactive
      substances (TBARS). The susceptibilities of several tissues to peroxidation were
      determined in tissue homogenates after in vitro lipid peroxidation. Antioxidant
      defence variables were evaluated by measuring plasma and heart vitamin E levels,
      and heart superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities.
      Higher plasma triacylglycerol (P<0.01) and TBARS (P<0.01) levels were found in
      rats fed the sucrose diet as compared with the starch-fed group, whereas plasma
      alpha-tocopherol levels were significantly decreased in the sucrose-fed group
      compared with the starch-fed group (P<0.01). Higher urine TBARS (P<0.01) were
      found in the sucrose-fed group compared with the starch-fed group, suggesting
      increased production of these substances from lipid peroxidation in vivo. Higher
      susceptibility to peroxidation in heart, thymus and pancreas was also found in
      the sucrose-fed group v. the starch-fed group. No statistical differences were
      observed for liver TBARS level between the two groups. Heart SOD activity was
      significantly decreased (P<0.001) in the sucrose-fed group compared with the
      starch-fed group, whereas heart vitamin E level and GPX activity were not
      different between the groups. However, the in vitro generation of superoxide
      radical in heart homogenate, measured by electron spin resonance detection and
      spin trapping, was not increased in the sucrose-fed group compared with starch
      fed rats. Altogether, the results indicate that a short-term consumption of a
      high-sucrose diet negatively affects the balance of free radical production and
      antioxidant defence in rats, leading to increased lipid susceptibility to
      peroxidation.

PMID- 12064344
TI  - Green tea extract only affects markers of oxidative status postprandially:
      lasting antioxidant effect of flavonoid-free diet.
AB  - Epidemiological studies suggest that foods rich in flavonoids might reduce the
      risk of cardiovascular disease and cancer. The objective of the present study was
      to investigate the effect of green tea extract (GTE) used as a food antioxidant
      on markers of oxidative status after dietary depletion of flavonoids and
      catechins. The study was designed as a 2 x 3 weeks blinded human cross-over
      intervention study (eight smokers, eight non-smokers) with GTE corresponding to a
      daily intake of 18.6 mg catechins/d. The GTE was incorporated into meat patties
      and consumed with a strictly controlled diet otherwise low in flavonoids. GTE
      intervention increased plasma antioxidant capacity from 1.35 to 1.56 (P<0.02) in
      postprandially collected plasma, most prominently in smokers. The intervention
      did not significantly affect markers in fasting blood samples, including plasma
      or haemoglobin protein oxidation, plasma oxidation lagtime, or activities of the
      erythrocyte superoxide dismutase, glutathione peroxidase, glutathione reductase
      and catalase. Neither were fasting plasma triacylglycerol, cholesterol, alpha
      tocopherol, retinol, beta-carotene, or ascorbic acid affected by intervention.
      Urinary 8-oxo-deoxyguanosine excretion was also unaffected. Catechins from the
      extract were excreted into urine with a half-life of less than 2 h in accordance
      with the short-term effects on plasma antioxidant capacity. Since no long-term
      effects of GTE were observed, the study essentially served as a fruit and
      vegetables depletion study. The overall effect of the 10-week period without
      dietary fruits and vegetables was a decrease in oxidative damage to DNA, blood
      proteins, and plasma lipids, concomitantly with marked changes in antioxidative
      defence.

PMID- 12064345
TI  - Glutamine metabolism in ovine splanchnic tissues: effects of infusion of ammonium
      bicarbonate or amino acids into the abomasum.
AB  - This study investigates the effects of increased NH3 or amino acid supply on
      glutamine utilisation and production by the splanchnic tissues of fed sheep. Six
      sheep, prepared with vascular catheters in the aorta, mesenteric, portal and
      hepatic veins, were fed grass pellets to 1.1 x energy maintenance requirements.
      Each treatment involved a 4 d abomasal infusion, of either ammonium bicarbonate
      (AMM; 234 micromol/kg(0.75 per min), water (CONT), or a mixture of amino acids
      that excluded glutamine and glutamate (AA; 46.8 micromol amino acid-N/kg(0.75)
      per min). The treatments simulated nutritional extremes in terms of the balance
      of absorbed N. Kinetics across the whole gut and the liver were monitored during
      an intra-jugular infusion of [5-(15N)]glutamine. Blood flow across the whole gut
      or liver were unaffected by treatment. Both AMM and AA infusions doubled the
      hepatic release of urea-N compared with CONT (P<0.02). AA infusion decreased
      arterial glutamine concentration by 26% (P<0.01) and 23 % (P<0.05) compared with
      AMM and CONT respectively. Despite this, whole-body glutamine flux was not
      affected by treatment. In contrast, AMM infusion increased hepatic glutamine
      production by 40% compared with CONT (P<0.02). This provided a mechanism to
      ensure NH3 supply to the periphery was maintained within the normal low
      physiological levels. Hepatic glutamine utilisation tended to increase during AA
      infusion, probably to ensure equal inflows of N to the ornithine cycle. Between 6
      and 10% of NH3 absorbed across the digestive tract was derived from the amido-N
      of glutamine. Overall, splanchnic glutamine utilisation accounted for 45-70% of
      whole-body glutamine flux.

PMID- 12064346
TI  - Oral ingestion of lactic-acid bacteria by rats increases lymphocyte proliferation
      and interferon-gamma production.
AB  - The effect of feeding lactic-acid bacteria on indices of functions of lymphocytes
      obtained from Peyer's patches, peripheral blood and spleen from inbred Wistar
      Furth rats were studied. Rats were fed on purified diets supplemented with 350 g
      milk or yoghurt/kg diet for 4 weeks. At the end of the feeding period, immune
      cells from the three sites were isolated and proliferation, interferon-gamma
      production and lymphocyte subset composition were studied. Rats consuming yoghurt
      had a greater in vitro proliferative response to yoghurt bacteria in the three
      lymphoid compartments, a greater interferon-gamma production in response to
      bacteria and concanavalin A in Peyer's patches and spleen, and a greater number
      of Peyer's patches B lymphocytes than milk-fed rats. Macrophage and T lymphocyte
      proportions and lymphocyte subset composition in the three sites were unaffected
      by yoghurt. These results indicate that feeding live bacteria contained in
      yoghurt may interact with the intestinal immune system, and influence the
      systemic immune system.

PMID- 12064347
TI  - The effects of dietary lipids on adrenergically-stimulated lipolysis in perinodal
      adipose tissue following prolonged activation of a single lymph node.
AB  - The effects of feeding beef suet (mostly saturated and monoenoic fatty acids),
      sunflower oil (rich in n-6 fatty acids) and fish oil (rich in n-3 fatty acids) on
      the response of mesenteric, omental, popliteal and perirenal adipocytes to
      experimentally-induced local inflammation were studied in adult guinea pigs.
      After 6 weeks on the experimental diets, the animals were fed standard chow, and
      lipopolysaccharide was injected unilaterally daily for 4 d to induce swelling of
      one popliteal lymph node. Basal lipolysis in the perinodal adipocytes of all
      depots studied was higher in the sunflower oil-fed animals than in the controls
      fed on standard chow, and lower in those fed on suet or fish oil. Dietary lipids
      altered rates of lipolysis during incubation with l0(-5) M noradrenaline in all
      samples studied from the locally-activated popliteal depot, but only in
      adipocytes within 5 mm of a large lymph node in the other depots. The fish-oil
      diet attenuated the spread of increased lipolysis within the locally-activated
      popliteal adipose tissue, and from this depot to other node-containing depots.
      These experiments show that n-6 polyunsaturated fatty acids promote and n-3 fatty
      acids suppress the spread of immune activation to adipocytes within and between
      depots, and alter the sensitivity of perinodal adipocytes to noradrenaline.
      Dietary effects are reduced or absent in adipocytes in sites remote from lymph
      nodes, and thus such samples do not adequately represent processes in perinodal
      adipose tissue. These results are consistent with the hypothesis that perinodal
      adipocytes interact with adjacent lymphoid cells during immune responses.

PMID- 12064348
TI  - Validation of a short food frequency questionnaire to assess folate intake.
AB  - A short quantitative food frequency questionnaire (FFQ) to assess folate intake
      was developed and validated against a 7-d weighed food intake record (7d-WR) and
      biochemical indices of folate status. Thirty-six men and women completed the self
      administered FFQ on two occasions a month apart, kept a 7d-WR and gave two
      fasting blood samples at the beginning and end of the study for measuring serum
      and erythrocyte folate, respectively. Mean folate intakes were similar by repeat
      FFQ and correlated strongly (r 077 and r 072, P<0.001, for men and women,
      respectively). All other comparisons were done using the results of the FFQ
      administered on the first occasion. Men reported similar folate intakes on the
      FFQ and 7d-WR, but women reported greater intakes on the FFQ compared with the 7d
      WR (P<0.05). There was a statistically significant correlation (partial,
      controlling for gender) between folate intakes reported by FFQ and 7d-WR (r 0.53,
      P<0.01). Folate intakes estimated by FFQ correlated significantly with serum (r
      0.47, P<0.01), but not erythrocyte folate (r 0.25, P>0.05), the strength of the
      association was greater in men than in women. Validity coefficients estimated
      using the method of triads were higher for the FFQ than for the 7d-WR when serum
      folate was used as the biomarker. Overall, these results suggest that this short
      FFQ is a useful method for assessing folate intake, particularly in men.

PMID- 12064349
TI  - Inhibition of the mitochondrial respiratory chain by phenylalanine in rat
      cerebral cortex.
AB  - Phenylketonuria (PKU) is biochemically characterized by the accumulation of
      phenylalanine (Phe) and its metabolites in tissues of affected children.
      Neurological damage is the clinical hallmark of PKU, and Phe is considered the
      main neurotoxic metabolite in this disorder. However, the mechanisms of
      neurotoxicity are poorly known. The main objective of the present work was to
      measure the activities of the mitochondrial respiratory chain complexes (RCC) and
      succinate dehydrogenase (SDH) in brain cortex of Wistar rats subjected to
      chemically induced hyperphenylalaninemia (HPA). We also investigated the in vitro
      effect of Phe on SDH and RCC activities in the cerebral cortex of 22-day-old
      rats. HPA was induced by subcutaneous administration of 2.4 micromol/g body
      weight alpha-methylphenylalanine, a phenylalanine hydroxylase inhibitor, once a
      day, plus 5.2 microM/g body weight phenylalanine, twice a day, from the 6th-21st
      postnatal day. The results showed a reduction of SDH and complex I + III activity
      in brain cortex of rats subjected to HPA. We also verified that Phe inhibited the
      in vitro activity of complexes I + III, possibly by competition with NADH.
      Considering the importance of SDH and RCC for the maintenance of energy supply to
      brain, our results suggest that energy deficit may contribute to the Phe
      neurotoxicity in PKU.

PMID- 12064350
TI  - Distribution of coenzyme Q homologues in brain.
AB  - Ubiquinone (coenzyme Q10), in addition to its function as an electron and proton
      carrier in mitochondrial electron transport coupled to ATP synthesis, acts in its
      reduced form (ubiquinol) as an antioxidant, inhibiting lipid peroxidation in
      biological membranes and protecting mitochondrial inner-membrane proteins and DNA
      against oxidative damage accompanying lipid peroxidation. Tissue ubiquinone
      levels are subject to regulation by physiological factors that are related to the
      oxidative activity of the organism: they increase under the influence of
      oxidative stress, e.g. physical exercise, cold adaptation, thyroid hormone
      treatment, and decrease during aging. In the present study, coenzyme Q homologues
      were separated and quantified in the brains of mice, rats, rabbits, and chickens
      using high-performance liquid chromatography. In addition, the coenzyme Q
      homologues were measured in cells such as NG-108, PC-12, rat fetal brain cells
      and human SHSY-5Y and monocytes. In general, Q1 content was the lowest among the
      coenzyme homologues quantified in the brain. Q9 was not detectable in the brains
      of chickens and rabbits, but was present in the brains of rats and mice. Q9 was
      also not detected in human cell lines SHSY-5Y and monocytes. Q10 was detected in
      the brains of mice, rats, rabbits, and chickens and in cell lines. Since both
      coenzyme Q and vitamin E are antioxidants, and coenzyme Q recycles vitamins E and
      C, vitamin E was also quantified in mice brain using HPLC-electrochemical
      detector (ECD). The quantity of vitamin E was lowest in the substantia nigra
      compared with the other brain regions. This finding is crucial in elucidating
      ubiquinone function in bioenergetics; in preventing free radical generation,
      lipid peroxidation, and apoptosis in the brain; and as a potential compound in
      treating various neurodegenerative disorders.

PMID- 12064351
TI  - Effects of bilobalide on hypoxia/hypoglycemia-stimulated glutamate efflux from
      rat cortical brain slices.
AB  - The aim of this study was to investigate the effects of bilobalide, the
      postulated active constituent of Ginkgo biloba, on the release of glutamate
      elicited by hypoxia/hypoglycemia. Cortical slices were prepared from rat brain
      and perfused with normal artificial cerebrospinal fluid (aCSF) or aCSF made
      hypoxic by gassing with nitrogen, and hypoglycemic by removal of glucose. The
      perfusate was assayed for glutamate by HPLC. After 30 minutes, perfusion with
      hypoxic/hypoglycemic aCSF glutamate levels in the perfusate were increased
      approximately 5-fold. Bilobalide at 1, 10, and 100 microM, when perfused together
      with hypoxic/hypoglycemic aCSF, significantly reduced the release of glutamate.
      This study suggests that the reported neuroprotective properties of bilobalide
      may, in part, be mediated through its ability to reduce glutamate efflux, thus
      leading to a decrease in the excitotoxic effects of this neurotransmitter.

PMID- 12064352
TI  - GABA(A) receptors in the pars compacta and GABA(B) receptors in the pars
      reticulata of rat substantia nigra modulate the striatal dopamine release.
AB  - The nigral GABAergic regulation of striatal dopamine release was investigated
      using voltammetry in freely moving rats. The local administration of muscimol (1
      nM) in the substantia nigra pars compacta, but not in the substantia nigra pars
      reticulata, increased the striatal dopamine release. In contrast, the
      administration of baclofen (10 nM) in the substantia nigra pars reticulata, but
      not in the substantia nigra pars compacta, produced a decrease of the striatal
      dopamine release. Opposite effects were respectively observed after
      administration of GABA(A) and GABA(B) antagonists. These data lead us to suggest
      a differential presynaptic GABAergic control of the dopaminergic
      neurotransmission through GABA(A) receptors in the substantia nigra pars
      compacta, and GABA(B) receptors in the substantia nigra pars reticulata.

PMID- 12064353
TI  - Distribution of the hypothalamic cardioactive hormone "G"-protein complex (PCG)
      in neuronal elements of the heart in intact and vagotomized rats.
AB  - The distribution of the protein-carrier of one of the coronary dilatatory
      glycopeptides, neurohormone "G" (PCG) in rat heart was examined by
      immunohistochemistry. PCG-immunoreactive nerve fibers and varicosities were found
      around cardiac ganglion cells and in close topographical contact with coronary
      vessels and capillaries of the heart. The anatomical localization of the PCG
      containing neuronal fibers was similar that of calcitonin gene-related peptide
      (CGRP) and neuropeptide Y (NPY); however, the intensity of the stainings were
      different. In contrast to NPY immunostainings, cardiac ganglion cells did not
      show any PCG immunoreactivity. Some of the small, SIF cell-like NPY
      immunopositive neurons were also immunostained to PCG. In the atrial
      cardiomyocytes, only ANP exhibited fairly intensive immunoreactivity. Fourteen
      days after vagotomy, no considerable changes were found in the distribution of
      PCG and other neuropeptides investigated in cardiac neurons and nerve fibers. The
      presence of PCG in cardiac neuronal elements suggests a possible role of this
      peptide in cardiovascular regulations.

PMID- 12064354
TI  - Involvement of amino-acid side chains of membrane proteins in the binding of
      glutathione to pig cerebral cortical membranes.
AB  - Glutathione (GSH), a general antioxidant and detoxifying compound, is the most
      abundant thiol-containing peptide in the central nervous system. It has been
      earlier shown to regulate the functions of glutamate receptors and to possess
      specific binding sites in both neurons and glial cells. The possible involvement
      of disulfide bonds, cysteinyl, arginyl, lysyl, glutamyl, and aspartyl residues in
      the binding of tritiated GSH to specific sites in pig cerebral cortical synaptic
      membranes was now studied after covalent modification of membrane proteins.
      Treatment of synaptic membranes with the thiol-modifying reagents 5,5'-dithio
      bis(2-nitrobenzoate) (DTNB) and 4,4'-dithiodipyridine (DDP) dramatically enhanced
      the binding of [3H]GSH in a dose-dependent manner. Dithiothreitol (DTT) alone
      reduced the binding, but pretreatment of the membranes with DTT potentiated the
      enhancing effect of DTNB. On the other hand, when the modification with DTNB was
      followed by treatment with DTT, the enhancement by DTNB was completely reversed.
      N-ethylmaleimide, a thiol alkylating agent, and phenylisothiocyanate, a thiol-
      and amino-group modifying compound, reduced the binding, and their effects were
      additive. The guanidino-modifying agent phenylglyoxal reduced the binding but the
      carboxyl-modifying reagent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide had no
      significant effect. The results indicate that cysteinyl side chains and disulfide
      bonds are essential in the binding of GSH to membrane proteins and that arginyl
      and lysyl side chains may also be directly involved in this process.

PMID- 12064356
TI  - The effects of lithium chloride and other substances on levels of brain N-acetyl
      L-aspartic acid in Canavan disease-like rats.
AB  - Canavan disease (CD) is a human early-onset leukodystrophy, genetic in nature and
      resulting from an autosomally inherited recessive trait. CD is characterized by
      loss of the axon's myelin sheath, while leaving the axons intact, and spongiform
      degeneration, especially in white matter. It is an osmotic disease that affects
      both gray and white matter and is caused by the inability of oligodendrocytes to
      hydrolyze N-acetyl-L-aspartate (NAA) because of a lack of aspartoacylase
      activity. As a result, there is a build-up of NAA in brain with both cellular and
      extracellular edema, as well as NAA acidemia and NAA aciduria. Recent studies
      have indicated that several compounds have the ability to reduce brain levels of
      NAA in normal mice and rats. In this investigation, these compounds have been
      tested, using a CD-like rat model of the human disease to evaluate their
      potential for use in the treatment of the disease. Of seven substances tested in
      an acute 5-day study, only lithium chloride treatment resulted in a significant
      reduction of about 13% in whole-brain NAA levels in the CD-like rat model. This
      is the first pharmacological investigation of the effect of drugs on the level of
      brain NAA in an animal model of CD, and the first report of a substance that can
      reduce the brain NAA level in this model.

PMID- 12064355
TI  - Ischemia-induced taurine release is modified by nitric oxide-generating compounds
      in slices from the developing and adult mouse hippocampus.
AB  - The novel neurotransmitter/neuromodulator nitric oxide (NO), which is linked to
      the activation of the N-methyl-D-aspartate class of glutamate receptors, has been
      shown to modify transmitter release in brain tissue. Release of the inhibitory
      amino acid taurine is also markedly enhanced by N-methyl-D-aspartate and NO
      producing agents under normal conditions in the mouse hippocampus. The release of
      preloaded [3H]taurine from hippocampal slices from adult (3-month-old) and
      developing (7-day-old) mice was characterized under ischemic conditions in the
      presence of different NO-generating compounds, hydroxylamine, sodium
      nitroprusside, and S-nitroso-N-acetylpenicillamine (SNAP), using a superfusion
      system. The ischemia-induced taurine release at both ages was markedly enhanced
      by 1.0 mM nitroprusside and 1.0 mM SNAP, whereas 5.0 mM hydroxylamine was
      effective only in adults. The nitroprusside- and SNAP-induced releases were
      reduced by the inhibitors of NO synthase (nitroarginine and 7-nitroindazole) and
      NO-sensitive soluble guanylyl cyclase [1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1
      one], suggesting involvement of the NO/cGMP pathway. The release in ischemia in
      the absence of Na+ was modified by NO compounds only in adults; the 0.1 mM N
      methyl-D-aspartate stimulated taurine release at both ages. The enhanced release
      of taurine associated with NO production could be beneficial to brain tissue
      under cell-damaging conditions and corroborates the neuroprotective role of this
      amino acid, particularly in the immature brain.

PMID- 12064358
TI  - Oxidative stress in synaptosomal proteins from mutant presenilin-1 knock-in mice:
      implications for familial Alzheimer's disease.
AB  - Presenilin-1 (PS-1) is a transmembrane protein that may be involved in the
      processing of amyloid precursor protein (APP). Mutations in PS-1 are the major
      cause of familial Alzheimer's disease (AD). AD brain is under significant
      oxidative stress, including protein oxidation. In the present study, protein
      oxidation was compared in synaptosomes from knock-in mice expressing mutant human
      PS-I (M146V mutation) and from wild-type mice expressing non-mutant human PS-1.
      Synaptosomal membrane protein conformational alterations associated with
      oxidative stress were measured using electron paramagnetic resonance (EPR) in
      conjunction with a protein-specific spin-label. Direct synaptosomal protein
      oxidation was assessed by a carbonyl detection assay. Synaptosomal proteins from
      PS-1 mutant mice displayed increased oxidative stress as measured by both
      techniques, compared with synaptosomal proteins from wild type mice. These data
      suggest that PS-1 mutations cause oxidative alterations in synaptosomal membrane
      protein structure and oxidative modification of synaptosomal proteins. Our
      findings suggest that familial AD may be associated with oxidative stress that
      may play a pivotal role in neuronal dysfunction and death.

PMID- 12064357
TI  - Sarin causes early differential alteration and persistent overexpression in mRNAs
      coding for glial fibrillary acidic protein (GFAP) and vimentin genes in the
      central nervous system of rats.
AB  - Neurotoxic effects of single dose of 0.5 x LD50 sarin (O
      isopropylmethylphosphonoflouridate) on central nervous system (CNS) of male
      Sprague-Dawley rats were studied. We investigated the mRNA expression of the
      astroglial marker genes glial fibrillary acidic protein (GFAP) and vimentin to
      evaluate the fate of astroglial and neuronal cells, because reactive gliosis is
      very often used to assess the extent of CNS damage. Rats were treated with 50
      microg/kg/ml of sarin and terminated at the time-points 1 and 2 hours and 1, 3,
      and 7 days post-treatment. Control rats were treated with normal saline. Total
      RNA was extracted and Northern blots were hybridized with cDNA probes for GFAP
      and vimentin, as well as 28S RNA (control). The data obtained indicate that a
      single dose of sarin (0.5 x LD50) showed induction in the transcript levels of
      GFAP and vimentin in the cortex, cerebellum, brainstem and midbrain, and spinal
      cord. The induction showed distinct spatial-temporal differences for each tissue
      studied. Both GFAP and vimentin were induced at 1 hour in all the tissues studied
      except brainstem, where moderate and high levels of GFAP induction were noted at
      1 and 3 days. Overexpressed transcript levels of GFAP and vimentin remained high
      in more responsive tissues such as the brainstem and midbrain. Other tissues,
      such as the cortex, spinal cord, and cerebellum showed a more downward trend for
      either GFAP or vimentin, or both, transcript levels at 7 days. It is noteworthy
      that both cortex (318 +/- 12%) and spinal cord (368 +/- 12%) showed relatively
      higher induction of GFAP, whereas cortex alone showed the highest level of
      overexpressed vimentin transcript levels (284 +/- 11%). Overall it is also clear
      that both GFAP and vimentin are needed for the effective recovery involving co
      ordinated alternating up- and downregulation of these two key astrocyte genes,
      depending on tissue specificity. The changes seen in the transcript levels of
      GFAP and vimentin may be the result of astrocyte dysfunction and loss,
      accompanied by compensatory proliferation and dedifferentiation of the astroglia.
      These changes could affect the neuronal cell types, thus altering the neuron-glia
      homeostasis.

PMID- 12064360
TI  - High-dose immunosuppression and hematopoietic stem cell transplantation in
      autoimmune disease: clinical review.
AB  - Since 1996, a number of investigators have carried out phase I-II studies of high
      dose immunosuppression with autologous hematopoietic stem cell transplantation
      (HSCT) in autoimmune diseases. Most of this activity has been in studies of
      multiple sclerosis (MS), systemic sclerosis (SSc), systemic lupus erythematosus
      (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA).
      Supported by animal models of antigen-induced autoimmunity, the rationale of HSCT
      is to time-shift the clinical autoimmunity to an earlier period, restoring self
      tolerance. Even with the considerable experience of more than 200
      transplantations since 1996, it is difficult to judge the optimal approach. This
      difficulty is in part because of the multiplicity of centers and protocols and
      the variability in patient eligibility and assessment, the extent of T-cell
      depletion, and the intensity of the preparatory regimens used. Other than that
      found in RA, treatment-related mortality has been higher than expected: 17% in
      SSc (with an additional 10% mortality from progressive disease), 13% in SLE, 13%
      in JIA, and 8% in MS. Protocol changes to improve safety have been instituted.
      These changes include the avoidance of high-dose rabbit antithymocyte serum in
      patients who received T-cell-depleted grafts, use of corticosteroids with
      granulocyte colony-stimulating factor during stem cell mobilization and as
      prophylaxis for the engraftment syndrome in MS, lung radiation shielding in SSc,
      and multiple precautions against the macrophage activation syndrome in JIA.
      Responses to primary and secondary endpoints have been seen, and there is a
      consensus among investigators and regulatory bodies that the time has come for
      randomized phase II-III studies. Each disease presents distinct difficulties: in
      MS, restriction of eligibility to patients with active inflammatory disease; in
      SSc, formulation of cardiopulmonary eligibility criteria to decrease risk; in
      SLE, judgment of whether HSCT adds any advantage to high-dose nonmyeloablative
      immunosuppressive treatment alone; and in RA, enhancement of response durability.
      All prospective randomized studies in these diseases must address problems in
      selection of the comparison nontransplantation treatment and appropriate stopping
      rules, particularly with treatment arms of unequal risk. Parallel trials in
      Europe and in the United States are in the late stages of design.

PMID- 12064361
TI  - Nonmyeloablative regimen preserves "niches" allowing for peripheral expansion of
      donor T-cells.
AB  - T-cell recovery following myeloablative preparatory regimens and cord blood
      transplantation in adult patients gen erally occurs between 1 and 3 years
      following allogeneic bone marrow transplantation. T-cell reconstitution may
      involve thymic education of donor-derived precursors or peripheral expansion of
      mature T-cells transferred in the graft. We measured quantitative and qualitative
      immunologic reconstitution, T-cell receptor spectratyping, and T-cell receptor
      excision circle (TREC) levels in adult recipients of umbilical cord blood
      transplants following a novel nonmyeloablative regimen. These results were
      compared to previously published results of similar patients receiving a
      myeloablative regimen and cord blood stem cells. With small numbers of patients
      treated so far, T-cells (CD3+) reached normal levels in adults 6 to 12 months
      following nonmyeloablative transplantation compared with 24 months in adults
      receiving a myeloablative regimen. At 12 months after transplantation, the
      numbers of phenotypically naive (CD45RA) T-cells were higher in those receiving
      the nonmyeloablative regimen. The T-cell repertoire in cord blood recipients
      treated with a nonmyeloablative regimen was markedly more diverse and robust
      compared with the repertoire in those receiving the myeloablative regimen at
      similar time points. TRECs (which are generated within the thymus and identify
      new thymic emigrants and those that have not divided) were detected 12 months
      after transplantation in the nonmyeloablative recipients, whereas TRECs were not
      detected in adults until 18 to 24 months in those receiving myeloablative
      regimens. Thus, in adults receiving a nonmyeloablative preparatory regimen, the
      quantitative and qualitative recovery of T-cells occurs through rapid peripheral
      expansion. The ability of patients receiving a nonmyeloablative regimen to
      recover within a few months suggests that the peripheral niches in which T-cells
      can proliferate are preserved in these patients compared to those receiving
      ablative regimens. Moreover, the presence of TREC-positive cells within 1 year
      suggests that thymic recovery is likewise accelerated in non myeloablative
      compared to myeloablative regimens.

PMID- 12064362
TI  - Searching for unrelated donor hematopoietic stem cells: availability and speed of
      umbilical cord blood versus bone marrow.
AB  - Unrelated donor (URD) umbilical cord blood (UCB) has several potential advantages
      over URD BM for hematopoietic stem cell transplantation. To examine the
      efficiency of donor identification for each of these URD stem cell sources, we
      reviewed the search processes for all pediatric and adult URD transplantation
      referrals to the University of Minnesota during a period of 1 year. Of 171
      consecutive referrals for URD transplantation, 108 patients proceeded to a formal
      URD search with selection of at least 1 donor. Significantly more formal UCB
      searches(54%) than BM searches (21%) were performed for patients who required
      urgent transplantation (P < .01). At least one 4-6/6 HLA-antigen matched UCB
      graft but no suitable BM graft was identified for 21 of the 108 patients (19%).
      The median time required to obtain a URD BM donor (from formal search to
      clearance of a BM donor) was 49 days (range, 32-293 days) compared to a UCB
      search time (from formal search to a donor unit chosen) of only 13.5 days (range,
      2-387 days). For patients undergoing both BM and UCB searches, 29 more days (95%
      confidence interval, 21-37 days) were required to identify and clear a URD BM
      donor than a UCB donor (P < .01). For the 76 patients who proceeded to
      transplantation, patients receiving UCB received a transplant a median of 25 days
      more rapidly than did those receiving BM (P < .01). These data confirm that the
      availability of banked cryopreserved URD UCB grafts allows transplantations for
      patients with no available BM donor and that URD UCB grafts areavailable
      considerably faster than are URD BM grafts. Faster availability is a particular
      advantage for patients requiring urgent transplantation. These unique features of
      UCB transplantation must be considered in comparisons of the outcomes of UCB
      versus BM transplant recipients and in the design of prospective trials comparing
      URD sources.

PMID- 12064359
TI  - Environmental estrogen-like chemicals and hydroxyl radicals induced by MPTP in
      the striatum: a review.
AB  - Oxygen free radical formation has been implicated in lesions caused by the 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and iron. Although MPTP
      produces a parkinsonian syndrome after its conversion to 1-methyl-4
      phenylpyridine (MPP+) by type B monoamine oxidase (MAO) in the brain, the
      etiology of this disease remains obscure. This review focuses on the role of an
      environmental neurotoxin chemically related to MPP+-induced free radical
      generation in the pathogenesis of Parkinson's disease. Environmental-like
      chemicals, such as para-nonylphenol or bisphenol A, significantly stimulated
      hydroxyl radical (*OH) formation in the striatum. Allopurinol, a xanthine oxidase
      inhibitor, prevents para-nonylphenol and MPP+-induced *OH generation. Tamoxifen,
      a synthetic nonsteroidal antiestrogen, suppressed the *OH generation via dopamine
      efflux induced by MPP+. These results confirm that free radical production might
      make a major contribution at certain stages in the progression of the injury.
      Such findings may be useful in elucidating the actual mechanism of free radical
      formation in the pathogenesis of neurodegenerative brain disorders, including
      Parkinson's disease and traumatic brain injuries.

PMID- 12064363
TI  - Comparison of outcome of allogeneic bone marrow transplantation with and without
      granulocyte colony-stimulating factor (lenograstim) donor-marrow priming in
      patients with chronic myelogenous leukemia.
AB  - To investigate the effect of granulocyte colony-stimulating factor (G-CSF) donor
      marrow priming on hematopoietic recovery and clinical outcome after allogeneic
      hematopoietic stem cell transplantation, we compared HILA-matched related marrow
      transplantation with and without G-CSF donor priming in a prospective randomized
      study for a homogeneous group of chronic myelogenous leukemia (CML) patients.
      Fifty patients (aged 12-41 years) with CML were enrolled in the study. Thirty-two
      patients (study group) received the marrow grafts primed with G-CSF at 3 to 4
      micro/kg per day for 7 days prior to the marrow harvest, and 18 patients (control
      group) received the marrow grafts without G-CSF priming. All patients received
      the same graft-versus-host disease (GVHD) prophylaxis (cyclosporine A and
      methotrexate) and postgraft G-CSF treatment, 3 to 4 micro/kg daily until the
      absolute neutrophil counts (ANCs) were >10(9)/L. The primary end points were
      engraftment and incidence of acute GVHD. The secondary end points were the
      incidence of chronic GVHD, relapse, and overall disease-free survival. The study
      and control groups were comparable for age, sex, donor selections, conditioning
      regimens, and disease status. The median times to both neutrophil and platelet
      engraftment (ANC > 0.5 x 10(9)/L; platelets > 20 x 10(9)/L) were significantly
      faster in the study group than in the control group, at 15 versus 21 days (P <
      .001) and 17.5 versus 24 days (P < .001), respectively. G-CSF donor printing
      yielded significantly higher numbers of total nuclear cells in the marrow grafts
      compared to the numbers in the control grafts (7.2 versus 2.9 x 10(8)/kg, P <
      .001). Similar results were seen for CD34+ (6.1versus 2.7 x 10(6)/kg, P < .001)
      and colony-forming unit-granulocyte/macrophage (CFU-GM) cells (68 versus 16 x
      10(4)/kg, P < .001). The incidence of grades II to IV acute GVHD was surprisingly
      low in the study group: only 2 (6.3%) of 32 transplantation patients in the study
      group developed grade II acute GVHD, limited to the skin, whereas 5 (27.8%) of 18
      patients in the control group developed grades II to IV acute GVHD (P = .032). G
      CSF priming did not change the total numbers of CD3+ cells in the marrow grafts
      but lowered CD4+ cells and increased CD8+ cells, resulting in a significant
      reduction of CD4:CD8 ratio (P = .018). Six patients in the study group developed
      chronic GVHD either during or after cyclosporine taper. There were no significant
      differences in chronic GVHD (24% versus 33.3%), relapse rates (12.5% versus
      11.1%), and overall survival rates (78.1% versus 66.7%, P = .32) between the
      study and control groups during a median follow-up period of 24 months (range, 6
      50 months). There was, however, a trend in favor of improved chronic GVHD and
      disease-free survival in the study group. We conclude that G-CSF donor-marrow
      priming accelerates both neutrophil and platelet engraftment and is associated
      with a very low incidence of grades II to IV acute GVHD in CML patients after HLA
      matched sibling marrow transplantation.

PMID- 12064364
TI  - Effect of prior therapy and bone marrow metastases on progenitor cell content of
      blood stem cell harvests in breast cancer patients.
AB  - This study was designed to examine the relationship of prior therapy, bone marrow
      metastases, mobilization, and blood progenitor/stem cell (BSC) collection in
      breast cancer patients. Cells were collected from 19 breast cancer patients
      during steady state (nonmobilized group) and from 69 breast cancer patients after
      cytokine administration (mobilized group). Characteristics of the patients were
      compared with the cells obtained. A significant inverse association was found
      between the number of chemotherapy regimens the patients had received prior to
      BSC collection and the mononuclear cell (MNC) count of the product per liter of
      blood processed (LBP) with apheresis (P = .0006) and the granulocyte
      monocyte/macrophage colony-forming cell (GM-CFC) numbers per LBP (P = .0002).
      This association was evident in both mobilized and nonmobilized patients. Similar
      results were seen in those 25 patients who had received prior radiation therapy
      (MNC/LBP, P = .0003; GM-CFC/LBP, P = .0004). Patients in both the mobilized and
      nonmobilized groups with marrow metastases at the time of collection also had
      significantly lower levels of MNC/LBP (P = .0039) and GM-CFC/LBP (P = .0001) than
      did those without marrow metastases. The findings suggest that prior
      administration of radiation therapy and/or chemotherapy and the presence of
      marrow metastases all negatively impacted the collection of mobilized and
      nonmobilized progenitor cells from breast cancer patients. The mechanisms of this
      impact are not understood.

PMID- 12064365
TI  - Autologous stem cell transplantation for small cell lung cancer.
AB  - Small cell lung cancer usually responds to radiation and chemotherapy, but cures
      are infrequent. Autotransplantation attempts to increase cures by intensifying
      the effects of chemotherapy. We studied 103 patients receiving high-dose
      chemotherapy with autologous hematopoietic stem cell transplantation (SCT) for
      small cell lung cancer in 1989-1997 at 22 centers participating in the Autologous
      Blood and Marrow Transplant Registry. Median age at transplantation was 50 years
      (range, 30-74 years). Fifty-five percent of patients were men. Forty-seven
      percent of patients underwent transplantation in 1989-1993 and 53% in 1994-1997.
      Most patients received peripheral blood stem cells alone (39%) or with bone
      marrow (44%); 18% received bone marrow alone. The 2 most common preparative
      regimens were cyclophosphamide/carmustine/cisplatin (CBP) (60%) and
      ifosfamide/carboplatin/etoposide (ICE) (28%). Median time from diagnosis to
      transplantation was 6 months (range, 1-34 months). Most patients underwent
      transplantation after partial response (66%) or complete response (27%) to
      combination therapy. The 100-day mortality was 11% (95% confidence interval [CI],
      6%-18%). Three-year probabilities of survival and progression-free survival (PFS)
      were 33% (95% CI, 24%-44%) and 26% (95% CI, 17%-36%), respectively, for all
      patients. Factors negatively associated with outcome in multivariate analysis
      were age greater than 50 years, extensive-stage disease at presentation, and
      preparative regimens other than CBP or ICE. Three-year survival and PFS rates
      were higher in patients with limited versus extensive disease, 43% versus 10% (P
      < .001) and 35% versus 4% (P < .001), respectively. Patients older than 50 years
      had nearly twice the risk of death or progression as younger patients (relative
      risk, 1.7; 95% CI, 1.1-2.8). Autologous SCT produces long-term survival in some
      patients with small cell lung cancer; SCT outcomes appear better in young
      patients with limited-stage disease. Transplantation for patients with extensive
      disease does not appear to produce substantial benefit.

PMID- 12064366
TI  - Infectious complications after autologous CD34-selected peripheral blood stem
      cell transplantation.
AB  - CD34 selection of peripheral hematopoietic blood stem cell products has been
      applied to reduce the risk of relapse after an autologous transplantation.
      However, CD34 selection is also associated with a significant reduction in T
      cells, natural killer cells, and monocytes, and these reductions may influence
      immune reconstitution and thus increase the risk for infections. An increased
      incidence of cytomegalovirus (CMV) disease in patients receiving CD34-selected
      transplants has been reported. In this study, the incidence rate of infections
      other than CMV is reported in 32 patients who underwent myeloablative therapy
      followed by the infusion of CD34-selected autologous peripheral blood stem cells
      (PBSC) and compared to the rate in a contemporaneous group of 273 patients who
      received unselected autologous PBSC during the same time period. Infection
      surveillance and prevention strategies were identical between the 2 groups. More
      non-CMV infections occurred in the recipients of CD34-selected PBSC than in
      recipients of unselected PBSC (78% versus 30%, P < .0001). The differences in the
      rates of viral infections were mainly due to dermatomal and disseminated
      varicella-zoster virus (VZV) (any VZV, 26% versus 4%, P = .002; disseminated VZV,
      11% versus 0.3%, P = .03) and parainfluenza 3 virus infections (13% versus 3%, P
      = .04). Bacterial infections were also more common among CD34-selected PBSC
      transplant recipients (34% versus 16%, P = .01), whereas fungal infections were
      not significantly different between the groups. In multivariable logistic
      regression models, the effect of CD34 selection on infection risk remained
      significant for viral infections and overall non-CMV infections. Infection
      related mortality was not significantly different between the groups. In
      conclusion, the incidence of viral and bacterial infections appears to be
      increased in recipients of CD34-selected autologous PBSC transplants. Because the
      risk for infections approaches that seen in allogeneic transplant recipients,
      infection surveillance, diagnostic work-up, and prevention strategies similar to
      those used in allogeneic recipients are warranted.

PMID- 12064367
TI  - Monoclonal anti-EGFreceptor antibody (ior-R3) pharmacokinetic study in tumor
      bearing nude mice: role of the receptor-mediated endocytosis on drug clearance.
AB  - With the purpose of describing the MAb ior-R3's kinetic behavior in disease
      state, this paper is focused on the study of this response using a human cancer
      (lung carcinoma cell line, H125) bearing nude mice animal model. This MAb was
      administered by a single 16 mg/Kg intravenous bolus dose and the blood samples
      were collected at several times ranging from 0 to 72 hours for serum drug
      quantification. The experimental data set was best fitted using a classical two
      compartment mammilary pharmacokinetic (PK) model and the corresponding PK
      parameters were determined. Comparatively, the analysis of the more relevant
      physiologically-based PK parameters showed a significant enhancing of clearance
      as compound with the earlier reported study on healthy mice, increasing from 0.09
      to 0.19 mL/h (p<0.01). However, the corresponding distribution volumes don't seem
      to be altered by the tumor xenograft. We conclude that all of these evidences
      suggest a possible mechanism of receptor-mediated endocytosis (RME) as a major
      cause of this increased drug clearance which also contributed to the faster
      decrease of the drug disposition.

PMID- 12064368
TI  - Phenacetin O-deethylation in extrahepatic tissues of rats.
AB  - Phenacetin O-deethylation is a marker reaction of CYP450 1A2 activity. The drug
      metabolizing enzyme is constitutively expressed in liver. In this study, an in
      vivo rat model for assessment of extrahepatic metabolism was used to investigate
      phenacetin O-deethylation and the alterations in the disposition of phenacetin
      due to the loss of liver function. Rats were divided into the model and normal
      control groups. The model was established according to our previously described
      method. The concentrations of phenacetin and its major metabolites acetaminophen,
      glucuronate-acetaminophen and sulfate-acetaminophen in plasma and urine were
      determined by HPLC. 30 min after intravenous administration of 0.16% phenacetin
      10 mg x kg(-1), plasma acetaminophen in the model group was only 3.6% of that in
      the control group (0.09+/-0.04 microg x mL(-1) vs 2.49+/-0.85 microg x mL(-1), n
      = 8). 30 min after intragastric injection of 0.4% phenacetin 30 mg x kg(-1),
      plasma acetaminophen formation was very slight, about 8.6% of plasma phenacetin
      in the model group (0.74+/-0.43 microg x mL(-1) acetaminophen vs 8.57+/-8.42
      microg x mL(-1) phenacetin) and 6.8% in the control group (1.06+/-0.59 microg x
      mL(-1) acetaminophen vs 15.47+/-7.21 microg x mL(-1) phenacetin, n = 8); no
      significant differences were observed in plasma phenacetin, total acetaminophen
      and the ratio of acetaminophen to phenacetin between control and model groups. In
      the urine collected for 3 h after intravenous administration of 0.16% phenacetin
      10 mg x kg(-1), the total recovery of acetaminophen (as free, glucuronate- and
      sulfate-acetaminophen ) in the model group was 4.6% of that in the control group
      (4.47+/-4.27 microg vs 96.63+/-8.50 microg, n = 6), but phenacetin recovery in
      the model group was 9 times higher than that in the control group (15.03+/-17.72
      microg vs 1.66+/-0.50 microg). The results indicate that phenacetin O
      deethylation in the extrahepatic tissues and the first-pass metabolism of the
      probe compound seem to be negligible in rats, but the renal excretion of
      phenacetin, as a compensation, dramatically increases in model rats.

PMID- 12064369
TI  - Squared correlation coefficient of measured values versus predicted values in
      linear and monoexponential regressions.
AB  - The correlation coefficient of measured values vs predicted values is widely used
      in pharmacokinetic and biopharmaceutical settings. When using linear and
      monoexponential regressions, we notice an interesting characteristic of the
      squared correlation coefficient of measured values vs predicted values, i.e. the
      squared correlation coefficient of measured y1 vs predicted (lambda)y2 is a
      constant regardless of different values of regression coefficients and is equal
      to the squared correlation coefficient of measured x1 vs measured y1.

PMID- 12064370
TI  - Drug interaction studies between paclitaxel (Taxol) and OC144-093--a new
      modulator of MDR in cancer chemotherapy.
AB  - The MDR modulator, OC144-093, is a potential candidate for use in cancer therapy
      and exhibits potent biological activity in vitro and in vivo when combined with
      anticancer agents such as paclitaxel. Its inhibitory interaction with P
      glycoprotein (Pgp), the mdr1 gene product and a mechanistic participant in
      multidrug resistance, underlies its activity as a modulator of MDR. Having
      previously shown that OC144-093 is not a substrate for CYP3A we first examined
      the effects of OC144-093 on paclitaxel metabolism in vitro. Using human liver
      microsomes, we have demonstrated that OC144-093 inhibited the CYP3A mediated
      metabolism of paclitaxel at high concentrations only (Ki = 39.8 +/- 5.1 microM,
      n=3). Pharmacokinetic results also show that an oral dose of OC144-093, co
      administered with paclitaxel caused negligible disturbance of the pharmacokinetic
      profile for paclitaxel when injected intravenously. In contrast, AUC values were
      elevated approximately 1.5-fold in all groups treated orally with paclitaxel and
      OC144-093. Cmax was enhanced approximately 2-fold in the co-dosed group. These
      characteristics are consistent with Pgp blockade in the gut enhancing oral
      bioavailability. Elimination properties of paclitaxel were affected only upon
      multiple dosing of OC 144-093. These results warrant the further clinical
      assessment of OC144-093 as an MDR reversing agent.

PMID- 12064371
TI  - Influence of dose on the disposition kinetics of netilmicin in the isolated
      kidney of the rat.
AB  - The disposition of Netilmicin in the isolated rat kidney was studied in order to
      determine the influence of dose on the drug profile in this tissue. Doses of 50,
      200, 800 or 10000 mg were injected through an afferent cannula into the isolated
      kidney as a bolus injection and outflow perfusate samples were collected.
      Statistical moments (AUC, MTT, VTT) were estimated from raw outflow curve data.
      Unit disposition function (UDF) was obtained by mass balance for each studied
      dose. The results of control assays addressing the viability of the isolated
      kidney preparations point to a high reproducibility for this preparation under
      the experimental conditions used, together with an acceptable viability.
      Comparison of statistical moments and derived parameters such as the extraction
      coefficient, distribution volume and drug renal clearance (E, Vd, ClE) suggest
      the existence of modifications in the distribution process with the dose, while
      elimination seems to remain unvariable; accordingly, the unit disposition
      function profiles were not superimposed for the different doses but differences
      during the early and final phases were observed.

PMID- 12064372
TI  - Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form
      indoxyl sulfate.
AB  - The aim of this study was to identify sulfotransferase (SULT) isoform(s)
      responsible for the formation of indoxyl sulfate from indoxyl (3-hydroxyindole).
      Indoxyl was incubated together with the co-substrate 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) and either human or rat liver cytosol or recombinant
      sulfotransferase enzymes. Formation of indoxyl sulfate from indoxyl was measured
      by HPLC and used for determination of sulfonation rates. Both cytosols sulfonated
      indoxyl with apparent Km values of 6.8 +/- 0.9 microM for human and 3.2 +/- 0.6
      microM for rat cytosol. To help identify the isoform(s) of SULT responsible for
      indoxyl sulfate formation, indoxyl was incubated with human and rat liver
      cytosols and PAPS in the presence of isoform-specific SULT inhibitors. No
      inhibition was observed by DHEA, a specific hydroxysteroid sulfotransferase
      inhibitor, nor by oestrone, an inhibitor of oestrogen sulfotransferase. However,
      an aryl (phenol) sulfotransferase inhibitor, 2,6-dichloro-4-nitrophenol (DCNP),
      inhibited the formation of indoxyl sulfate with a IC50 values of 3.2 microM for
      human and 1.0 microM for rat cytosol indicating that human and rat aryl (phenol)
      sulfotransferases are responsible for the formation of indoxyl sulfate. When
      indoxyl was incubated with SULT1A1*2, a human recombinant aryl SULT, an apparent
      Km value of 5.6 +/- 1.8 microM was obtained. Kinetic studies with human and rat
      cytosols and human recombinant SULT1A1*2 gave similar kinetic values indicating
      that human and rat aryl sulfotransferases efficiently catalyze the formation of
      indoxyl sulfate, an important uremic toxin metabolite.

PMID- 12064373
TI  - The effect of heat stress on the induced hepatic drug metabolizing system in
      rats.
AB  - The activity of the hepatic oxidative drug metabolizing system has been
      investigated in an experimentally-induced heat stress animal model pretreated
      with phenobarbitone. Female rats, unacclimatized and untrained were pretreated
      for 3 days with phenobarbitone as the inducing agent for the drug metabolizing
      systems. On the fourth day, they were restrained and exposed to an ambient
      temperature of 40 degrees C. One hour after acute exposures to such conditions,
      the activities of hepatic cytochrome P450, cytochrome b5 and NADPH cytochrome c
      reductase were significantly decreased in the induced animal model. Further,
      cytochrome P450 isozymes observed by SDS-gel electrophoresis were significantly
      decreased. In addition, the hypnotic effect of pentobarbitone was significantly
      increased. It is concluded that the activity of the hepatic oxidative drug
      metabolizing enzymes was decreased in induced drug metabolism systems exposed to
      heat stress conditions.

PMID- 12064374
TI  - Estimation of basic uncertainties in clinical analysis.
AB  - Clinical analyses have a vital importance in human health. Thus, it is necessary
      to have reliable analytical information which depends on a good assessment of
      accuracy and this can be obtained by minimization of uncertainty values. The
      uncertainty values are complex and arise from different sources such as sample,
      method, instrumentation and data processing. Some of these components may have
      been evaluated from the distribution of results of series of measurements and can
      be characterized by standard deviations. In our laboratory, for example the
      balance calibration uncertainty for 1 g was found to be 0.00414 g. The
      uncertainties for the volume of solution contained in a 100 mL volumetric flask
      and a 0.5 mL glass-pipette were calculated to be 0.0843 mL and 0.0071 mL
      respectively and etc.

PMID- 12064375
TI  - The influence of cardiac output distribution on the tissue/plasma drug
      concentration ratio.
AB  - In pharmacokinetics, it is currently assumed that blood and interstitial spaces
      belong to the central compartment, when the solute is quickly equilibrated
      between both fluids. Taking into account that the same extracellular fluid
      dissolves the drug either in the plasma or in the interstitium, both drug
      concentrations (intra and intravascular) should be identical. However, this
      equality may not exist when there is a dissimilar distribution of blood flow
      among the organs. A closed, two-zone, three-compartment model was mathematically
      investigated. Compartment 1 was intravascular, and compartments 2 and 3 were
      extravascular. The fluid within the compartment 1 was supposed to be pushed by a
      pump, and to be distributed towards two different zones. One of these zones was
      in contact with the compartment 2, and the other with compartment 3. The drug
      could be exchanged between the compartments 1 and 2 or 1 and 3, by mean of first
      order kinetics (k12, k21, k13, k31). It was assumed a very fast flow that assured
      instantaneous homogeinity of drug concentration in compartment 1. Pressure was
      kept constant, so an increase in the pump output distribution towards one zone is
      compensated by a decrease towards the other zone. At time infinite the drug
      concentration (C) ratio between compartments yielded: C2/C1 =
      k12.sigma.V1/(k21.V2) and C3/C1 = k13.(1-sigma).V1/(k31.V3), being sigma: the
      pump output fraction served to the zone where compartment 2 was located, and Vi:
      the volumes of compartments. So, at the equilibrium the concentrations are not
      necessarily identical between the extravascular and intravascular sites. In
      conclusion, as the cardiac output distribution changes due to circadian rythms
      and cardiovascular active drug administration, current therapeutic drug
      monitoring and bioequivalence studies using plasma as biologic fluid would be
      controversial issues.

PMID- 12064376
TI  - Pharmacokinetics of phenytoin following intravenous and intramuscular
      administration of fosphenytoin and phenytoin sodium in the rabbit.
AB  - The purpose of this study was to evaluate and compare plasma phenytoin
      concentration versus time profiles following intravenous (i.v.) and intramuscular
      (i.m.) administration of fosphenytoin sodium with those obtained following
      administration of standard phenytoin sodium injection in the rabbit. Twenty-four
      adult New Zealand White rabbits (2.1 +/- 0.4 kg) were anaesthetized with sodium
      pentobarbitone (30 mg/kg) followed by i.v. or i.m. administration of a single 10
      mg/kg phenytoin sodium or fosphenytoin sodium equivalents. Blood samples (1.5 ml)
      were obtained from a femoral artery cannula predose and at 1, 3, 5, 7, 10, 15,
      20, 30, 45, 60, 90, 120, 180, 240 and 300 min after drug administration. Plasma
      was separated by centrifugation (1000 g; 5 min) and fosphenytoin, total and free
      plasma phenytoin concentrations were measured using high performance liquid
      chromatography (HPLC). Following i.v. administration of fosphenytoin sodium
      plasma phenytoin concentrations were similar to those obtained following i.v.
      administration of an equivalent dose of phenytoin sodium. Mean peak plasma
      phenytoin concentrations (Cmax) was 158% higher (P = 0.0277) following i.m.
      administration of fosphenytoin sodium compared to i.m. administration of
      phenytoin sodium. The mean area under the plasma total and free phenytoin
      concentration-time curve from time zero to 120 min (AUC(0-120)) following i.m.
      administration was also significantly higher (P = 0.0277) in fosphenytoin treated
      rabbits compared to the phenytoin group. However, there was no significant
      difference in AUC(0-180) between fosphenytoin and phenytoin-treated rabbits
      following i.v. administration. There was also no significant difference in the
      mean times to achieve peak plasma phenytoin concentrations (Tmax) between
      fosphenytoin and phenytoin-treated rabbits following i.m. administration. Mean
      plasma albumin concentrations were comparable in both groups of animals.
      Fosphenytoin was rapidly converted to phenytoin both after i.v. and i.m.
      administration, with plasma fosphenytoin concentrations declining rapidly to
      undetectable levels within 10 min following administration via either route.
      These results confirm the rapid and complete hydrolysis of fosphenytoin to
      phenytoin in vivo, and the potential of the i.m. route for administration of
      fosphenytoin delivering phenytoin in clinical settings where i.v. administration
      may not be feasible.

PMID- 12064378
TI  - Topical meeting on optical interference coatings (OIC'2001): design contest
      results.
AB  - A gain-flattening filter (GFF) for minimum manufacturing errors (12 designs
      submitted) and dense wavelength-division multiplex (DWDM) filters for low group
      delay (GD) variation (9 designs submitted) was the subject of a design contest
      held in conjunction with the Optical Interference Coatings 2001 topical meeting
      of the Optical Society of America. Results of the contest are given and
      evaluated. It turned out that the parameter space for GFFs with optimum
      performance when manufacturing errors are not considered is much different from
      that when manufacturing errors are considered. DWDM filter solutions with low GD
      variation are possible.

PMID- 12064377
TI  - Comparative bioavailability of two immediate release tablets of
      enalapril/hydrochlorothiazide in healthy volunteers.
AB  - A bioequivalence study of two oral formulations of 20/12.5 mg tablets of
      enalapril/hydrochlorothiazide was carried out in 20 healthy male volunteers
      according to a single dose, two-sequence, crossover randomized design. One
      washout period of nine days was observed between the two periods. Multiple
      samples were collected over 96 hours post-dosing. Bioavailability was evaluated
      on the basis of plasma concentrations of enalapril and its main active
      metabolite, enalaprilat and hydrochlorothiazide. Plasma samples were assayed for
      enalapril, enalaprilat and hydrochlorothiazide using a selective and sensitive
      high-performance liquid chromatography method with mass spectrometry detection
      (LC-MS). The pharmacokinetic parameter values of Cmax and tmax were obtained
      directly from plasma data, k(e) was estimated by log-linear regression, and AUC
      was calculated by trapezoidal rule. Different statistical tests were performed on
      the basis of untransformed and log-transformed data and the overall residual
      variance from ANOVA. Assuming the accepted tolerance intervals, a beta-error of
      20% and 90% confidence intervals (alpha = 0.10), all the generally accepted tests
      (Schuirmann test and Wilcoxon-Tukey and Hauschke nonparametric tests) showed that
      the formulations can be considered as bioequivalent with respect to the extent of
      absorption, given by the AUC(0-infinity) and with respect to rate of absorption
      as assessed by Cmax and tmax.

PMID- 12064379
TI  - Topical meeting on optical interference coatings (OIC'2001): manufacturing
      problem.
AB  - Measurements are presented of the experimental filters submitted to the first
      optical thin-film manufacturing problem posed in conjunction with the Topical
      Meeting on Optical Interference Coatings, in which the object was to produce
      multilayers with spectral transmittance and reflectance curves that were as close
      as possible to the target values that were specified in the 400- to 600-nm
      spectral region. No limit was set on the overall thickness of the solutions or
      the number of layers used in their construction. The participants were free to
      use the coating materials of their choice. Six different groups submitted a total
      of 11 different filters for evaluation. Three different physical vapor deposition
      processes were used for the manufacture of the coatings: magnetron sputtering,
      ion-beam sputtering, and plasma-ion-assisted, electron-beam gun evaporation. The
      solutions ranged in metric thickness from 758 to 4226 nm and consisted of between
      8 and 27 layers. For all but two of the samples submitted, the average rms
      departure of the measured transmittances and reflectances from the target values
      in the spectral region of interest was between 0.98% and 1.55%.

PMID- 12064380
TI  - Review of the fundamentals of thin-film growth.
AB  - The properties of a thin film of a given material depend on the film's real
      structure. The real structure is defined as the link between a thin film's
      deposition parameters and its properties. To facilitate engineering the
      properties of a thin film by manipulating its real structure, thin-film formation
      is reviewed as a process starting with nucleation followed by coalescence and
      subsequent thickness growth, all stages of which can be influenced by deposition
      parameters. The focus in this review is on dielectric and metallic films and
      their optical properties. In contrast to optoelectronics all these film growth
      possibilities for the engineering of novel optical films with extraordinary
      properties are just beginning to be used.

PMID- 12064381
TI  - Deposition of a conductive near-infrared cutoff filter by radio-frequency
      magnetron sputtering.
AB  - We have designed a conductive near-infrared (NIR) cutoff filter for display
      application, i.e., a modified low-emissivity filter based on the three periods of
      the basic design of [TiO2[Ti]Ag] TiO2] upon a glass substrate and investigated
      the optical, structural, chemical, and electrical properties of the conductive
      NIR cutoff filter prepared by a radio frequency magnetron sputtering system. The
      results show that the average transmittance is 61.1% in the visible, that the
      transmittance in the NIR is less than 6.6%, and that the sheet resistance and
      emissivity are 0.9 ohms/square (where square stands for a square film) and 0.012,
      respectively, suggesting that the conductive NIR cutoff filter can be employed as
      a shield against the hazard of electromagnetic waves as well as to cut off the
      NIR.

PMID- 12064382
TI  - Gradually layered alternated-substrate synthesis.
AB  - Gradually layered alternated-substrate synthesis (GLASS) is an automatic design
      method for optical coatings, which permits a gradual increase in the layer count
      of a stack while its optical properties are improved. This method does not
      require any starting design but only the design target and the list of allowed
      coating materials. In contrast to the needle technique, in which the coating is
      optimized between its two real external media, with new layers added inside the
      coating, the GLASS method adds new layers at the end of the design and uses
      coating materials as one external medium. This external medium provides new
      layers and is changed for another coating material each time a new layer is
      added. At the end, the coating must be matched to the real external medium that
      was not used during the design procedure.

PMID- 12064383
TI  - Toward perfect antireflection coatings: numerical investigation.
AB  - A perfect antireflection (AR) coating would remove completely the reflection from
      an interface between two media for all wavelengths, polarizations, and angles of
      incidence. The degree to which this can be achieved is investigated numerically.
      It is shown that wideband solutions can be found provided that layers can be
      deposited with refractive indices that are close to that of the low-index medium.
      Thus realistic solutions exist for interfaces between two solid media. Narrow
      band high-angle AR solutions are also possible for polarized light and for
      unpolarized light in the vicinity of certain reststrahlen bands.

PMID- 12064384
TI  - Theoretical study of amplitude and phase filtering of guided waves.
AB  - The design of integrated optics filters by use of refinement software based on
      the Abeles thin-film computation method and the film mode matching method is
      studied. The results obtained with the two computation methods are compared. Good
      agreement is obtained provided that the fill factor of the guided mode in the
      component is high and that modal losses between waveguide sections are simulated
      by absorption with the Abeles computation method. Integrated optics devices that
      manage either the amplitude of guided waves such as a dense wavelength division
      multiplexing narrow-bandpass filter and a gain-flattening filter or the phase of
      guided waves such as a broadband dispersion compensator are

PMID- 12064385
TI  - Design of a robust thin-film interference filter for erbium-doped fiber amplifier
      gain equalization.
AB  - Gain-flattening filters (GFFs) are key wavelength division multiplexing
      components in fiber-optics telecommunications. Challenging issues in the design
      of thin-film GFFs were recently the subject of a contest organized at the 2001
      Conference on Optical Interference Coatings. The interest and main difficulty of
      the proposed problem was to minimize the sensitivity of a GFF to simulated
      fabrication errors. A high-yield solution and its design philosophy are
      described. The approach used to control the filter robustness is explained and
      illustrated by numerical results.

PMID- 12064386
TI  - Design and manufacture of spectrally selective reflecting coatings for the use
      with laser display projection screens.
AB  - To provide screens for laser projection that improve contrast, a spectrally
      selective reflecting filter was designed by using genetic algorithms to overcome
      the problem of unknown starting values. Colormetrics rather than fixed targets
      were used for evaluation. Various selective filters were deposited upon glass as
      well as upon solid and flexible plastic substrates by reactive mid-frequency
      magnetron sputtering. For process control, in situ spectroscopic ellipsometry was
      applied.

PMID- 12064387
TI  - Antireflection coating design for plastic optics.
AB  - The coating of plastics for optical applications is intended to improve the
      mechanical durability of soft polymers and to serve an antireflection function.
      Usually a classic four-layer antireflection system is added on top of a single
      layer hard coating. With needle optimization, an alternative coating design has
      been developed. The design is characterized by thin high-refractive-index layers
      that are almost evenly distributed over the whole stack. Plasma ion-assisted
      deposition was used to deposit coatings upon poly(methyl methacrylate),
      polycarbonate, and cyclo-olefin copolymer. Uniform antireflection and high
      scratch resistance have been achieved.

PMID- 12064388
TI  - Expressions for determination of layer absorbances of a weakly absorbing double
      layer sample through reflectance at the Brewster angles.
AB  - A new technique for determining absorbances of interferenceless (incoherent)
      layers based on measurements of the ratio of the front and the back
      reflectivities of a double-layer sample at the Brewster angles is proposed. A
      double-layer stack must have at least one absorbing layer, and the two layers
      should be interferenceless and should be thicker than the wavelength of the
      incident light. We found that under these conditions the ratio of the front and
      the back reflectivities at the Brewster angle of a sample surface is directly
      related to layer absorbance. For a layer with a known thickness this means
      finding the extinction coefficient of the layer material. In comparison with the
      conventional method for measuring transmittance, the advantage of this approach
      is that it affords an opportunity to get rid of the influence of surface effects
      on the measuring volume absorption coefficient. For a thick layer with known
      thickness, it makes possible the determination of a small bulk absorption on a
      background with even greater surface effects. We trust that this technique will
      prove to be powerful for measuring the extinction coefficients of weakly
      absorbing materials.

PMID- 12064389
TI  - Multiwavelength imaging of defects in ultraviolet optical materials.
AB  - Laser-induced damage in bare glass substrates and thin films has long been widely
      acknowledged as a localized phenomenon associated with the presence of micrometer
      and submicrometer scale defects. The scanning of both optical absorption and
      scattering allows us to discriminate between absorbing and nonabsorbing defects
      and can give specific information about the origin of the defects. We investigate
      the spectral properties of defects in thin films and fused-silica surfaces.
      Absorbing and scattering defects are studied at different wavelengths in the
      ultraviolet, visible, and infrared ranges. Absorbing defects are shown to be
      highly wavelength dependent, whereas we have observed significant correlation
      between scattering defects.

PMID- 12064390
TI  - Guided-wave technique for the measurement of dielectric thin-film materials'
      thermal properties.
AB  - A pump-and-probe setup that uses a totally reflecting prism coupler is presented.
      Its electromagnetic and thermal models are described. To our knowledge, the first
      results are given concerning the measurement of thermal properties of thin films.

PMID- 12064391
TI  - Deltan/deltaT measurements performed with guided waves and their application to
      the temperature sensitivity of wavelength-division multiplexing filters.
AB  - Measurements of deltan/deltaT of thin films by the m-lines technique are
      presented. The importance of the substrate material is shown. An example of the
      wavelength shift of an optical thin-film filter with temperature is studied both
      theoretically and experimentally. The theoretical wavelength shift of a dense
      wavelength-division multiplexing filter is discussed.

PMID- 12064392
TI  - Application of the Tauc-Lorentz formulation to the interband absorption of
      optical coating materials.
AB  - Recent progress in ellipsometry instrumentation permits precise measurement and
      characterization of optical coating materials in the deep-UV wavelength range.
      Dielectric coating materials exhibit their first electronic interband transition
      in this spectral range. The Tauc-Lorentz model is a powerful tool with which to
      parameterize interband absorption above the band edge. The application of this
      model for the parameterization of the optical absorption of TiO2, Ta2O5, HfO2,
      Al2O3, and LaF3 thin-film materials is described.

PMID- 12064393
TI  - Pit formation observed in a multilayer dielectric coating as a result of
      simulated space environmental exposure.
AB  - Certain spaceborne telescope designs require that dielectric-coated lenses be
      exposed to the energetic electrons and protons associated with the space
      environment. Test coupons that were exposed to a simulated space environment
      showed extensive pitting as a result of dielectric breakdown. A typical pit was
      50-100 microm at the surface and extended to the substrate material, in which a
      10-microm-diameter melt region was found. Pitting was not observed on similar
      samples that had also been overcoated with a transparent conductive thin film.
      Measurement of the bidirectional reflectance distribution transfer function
      showed that pitting caused a fivefold to tenfold increase in the scattering of
      visible light.

PMID- 12064394
TI  - Simulated space environmental exposure of optical coatings for spacecraft solar
      rejection.
AB  - Dielectric multilayers composed of niobium pentoxide and silicon dioxide,
      designed for broadband solar rejection, were exposed to a simulated space
      environment of ultraviolet light and low-energy (10-20-keV) electron radiation.
      Samples exhibited various degrees of exposure-induced absorption extending from
      the ultraviolet to the infrared. Processing variations were correlated to damage
      susceptibility, and methods were identified that produced parts that exhibited no
      degradation even though the same materials and coating design were used. Coatings
      prepared under energetic deposition conditions that provided the densest and most
      moisture-stable coatings exhibited the best stability to the exposure conditions
      used.

PMID- 12064395
TI  - Laser-induced damage of materials in bulk, thin-film, and liquid forms.
AB  - Accurate threshold curves of laser-induced damage (7-ns single shot at 1.064
      microm) are measured in bulk and at the surfaces of optical components such as
      substrates, thin films, multilayers, and liquids. The shapes and the slopes of
      the curves are related to the spot size and to the densities of the nanodefects
      that are responsible for damage. First, these densities are reported for bulk
      substrates. In surfaces and films the recorded extrinsic and intrinsic threshold
      curves permit the discrimination of the effects of microdefects and nanodefects.
      In all cases the density of nanocenters is extracted by means of a
      phenomenological approach. Then we test liquids and mixtures of liquids with
      controlled defect densities. The results emphasize the agreement between
      measurement and prediction and demonstrate the validity of the presence of
      different kinds of nanocenter as the precursors of laser damage.

PMID- 12064396
TI  - Single-layer model for surface roughness.
AB  - Random roughness of an optical surface reduces its specular reflectance and
      transmittance by the scattering of light. The reduction in reflectance can be
      modeled by a homogeneous layer on the surface if the refractive index of the
      layer is intermediate to the indices of the media on either side of the surface.
      Such a layer predicts an increase in the transmittance of the surface and
      therefore does not provide a valid model for the effects of scatter on the
      transmittance. Adding a small amount of absorption to the layer provides a model
      that predicts a reduction in both reflectance and transmittance. The absorbing
      layer model agrees with the predictions of a scalar scattering theory for a layer
      with a thickness that is twice the rms roughness of the surface. The extinction
      coefficient k for the layer is proportional to the thickness of the layer.

PMID- 12064397
TI  - Group delay and chromatic dispersion of thin-film-based, narrow bandpass filters
      used in dense wavelength-division-multiplexed systems.
AB  - Theoretical analysis is made for thin-film-based, 200- and 100-GHz narrow
      bandpass filters with respect to the intensity response as well as to the
      chromatic dispersion. The results indicate that the narrower the passband, the
      higher the chromatic dispersion. The maximum chromatic dispersion appears at the
      edges of the 0.5-dB passband, owing to the fast change of the group delay in the
      region. The deviation of chromatic dispersion induced by manufacturing error is
      simulated. Effective-medium approximation layers are added to simulate the
      contribution of surface roughness and the mixture interfaces to the passband
      ripple as well as the chromatic dispersion. The simulations are compared with the
      experimental results. The measured chromatic dispersion matches the general trend
      of the theoretical calculation. The imperfect surface and layer mismatch induce
      additional ripples across the 0.5-dB passband. The maximum chromatic dispersion
      within a 0.5-dB passband is 20.7 and 54.9 ps/nm for 200- and 100-GHZ narrow
      bandpass filters, respectively.

PMID- 12064399
TI  - Design of reflective phase compensator filters for telecommunications.
AB  - Reflective phase compensator (RPC) filters provide a solution to the phase
      dispersion problem of narrow bandpass (NBP) filters when the data rate is 40
      Gbits/s or greater. By use of an RPC filter to compensate for the excessive group
      delay (GD) ripple of an NBP filter, the GD ripple of the combined NBP+RPC filter
      is well under the required 2.5 ps.

PMID- 12064398
TI  - Automated design and sensitivity analysis of wavelengh-division multiplexing
      filters.
AB  - An automated approach to the design of wavelength-division multiplexing (WDM)
      filters is based on the combination of ideas from classical design approaches
      with an integer optimization technique. This approach turns out to be extremely
      efficient from a computational point of view and makes it possible to construct a
      set of significantly different filter designs with nearly equivalent spectral
      properties. The sensitivity of WDM filters is analyzed by a computer simulation
      of the deposition process with turning-point optical monitoring. This analysis
      enables the designer to compare feasibility properties of various filter designs.

PMID- 12064400
TI  - Design of omnidirectional high reflectors with quarter-wave dielectric stacks for
      optical telecommunication bands.
AB  - A design for omnidirectional high reflectors with quarter-wave dielectric stacks
      in the optical telecommunication band that uses conventional optical thin-film
      design theory is described. The omnidirectional bandwidth is derived in units of
      wavelength and investigated as a function of its high- and low-refractive-index
      values in the near infrared. The results show that the high refractive index
      should be larger than 2.26 for an omnidirectional high reflector and that the low
      refractive index for maximum onmidirectional bandwidth should be approximately
      1.5. It is shown that one can design broad-bandwidth omnidirectional high
      reflectors for S, C, and L bands for optical telecommunication simply by
      connecting the band edges of omnidirectional high reflectors.

PMID- 12064401
TI  - Simulation of errors in the monitoring of narrow bandpass filters.
AB  - Narrow bandpass filters are extremely sensitive to errors in the optical
      thickness of the layers, but they have an extraordinary inherent capability to
      compensate for these errors. Graphical examples of errors of differing magnitudes
      and types with and without compensation are shown with computer simulation of the
      optical monitoring techniques. This allows the estimation of what magnitude of
      errors may be tolerable in given applications.

PMID- 12064402
TI  - Ultraviolet optical and microstructural properties of MgF2 and LaF3 coatings
      deposited by ion-beam sputtering and boat and electron-beam evaporation.
AB  - Single layers of MgF2 and LaF3 were deposited upon superpolished fused-silica and
      CaF2 substrates by ion-beam sputtering (IBS) as well as by boat and electron beam
      (e-beam) evaporation and were characterized by a variety of complementary
      analytical techniques. Besides undergoing photometric and ellipsometric
      inspection, the samples were investigated at 193 and 633 nm by an optical scatter
      measurement facility. The structural properties were assessed with atomic-force
      microscopy, x-ray diffraction, TEM techniques that involved conventional thinning
      methods for the layers. For measurement of mechanical stress in the coatings,
      special silicon substrates were coated and analyzed. The dispersion behavior of
      both deposition materials, which was determined on the basis of various
      independent photometric measurements and data reduction techniques, is in good
      agreement with that published in the literature and with the bulk properties of
      the materials. The refractive indices of the MgF2 coatings ranged from 1.415 to
      1.440 for the wavelength of the ArF excimer laser (193 nm) and from 1.435 to
      1.465 for the wavelength of the F2 excimer laser (157 nm). For single layers of
      LaF3 the refractive indices extended from 1.67 to 1.70 at 193 nm to approximately
      1.80 at 157 nm. The IBS process achieves the best homogeneity and the lowest
      surface roughness values (close to 1 nm(rms)) of the processes compared in the
      joint experiment. In contrast to MgF2 boat and e-beam evaporated coatings, which
      exhibit tensile mechanical stress ranging from 300 to 400 MPa, IBS coatings
      exhibit high compressive stress of as much as 910 MPa. A similar tendency was
      found for coating stress in LaF3 single layers. Experimental results are
      discussed with respect to the microstructural and compositional properties as
      well as to the surface topography of the coatings.

PMID- 12064403
TI  - Ion-assisted deposition of moisture-stable hafnium oxide films for ultraviolet
      applications.
AB  - A design-of-experiments statistical approach was taken to determine the optimum
      ion gun operating parameters for the deposition of moisture-stable, low-absorbing
      hafnium oxide films by ion-assisted electron-beam evaporation. Factors identified
      as affecting the quality of hafnia films were chamber pressure, deposition rate,
      ion gun source gas composition, and ion gun current. Both oxygen and argon were
      used as source gases. High and low levels of the factors were chosen on the basis
      of our experience with the operating range of the system, and we made a series of
      24 runs with all possible combinations of these factors. From a statistical
      analysis of the data, we find that the best films are obtained with a 1:1 mixture
      of argon and oxygen, 3-3.5 x 10(-4) Torr chamber pressure, 0.3-nm/s deposition
      rate, and 0.5-A ion gun current. X-ray diffraction measurements show that the ion
      assisted films exhibit a partial monoclinic crystalline structure, whereas the
      unassisted films are amorphous.

PMID- 12064404
TI  - Mechanical stress and thermal-elastic properties of oxide coatings for use in the
      deep-ultraviolet spectral region.
AB  - Mechanical stress and the structures of SiO2, Al2O3, and HfO2 single oxide layers
      and of high-reflection multilayer coatings deposited by reactive evaporation,
      plasma ion-assisted deposition, and ion-beam sputtering have been studied. The
      stress was related to the microstructure and to the incorporation of water by
      means of infrared spectroscopy. From the slopes of measured stress-temperature
      curves of these coatings deposited onto two substrate materials (silicon and
      fused silica), the biaxial moduli and the thermal expansion coefficients of the
      films were estimated.

PMID- 12064405
TI  - Long-wavelength polarizing cutoff filters for the 275-550-nm spectral region.
AB  - The design and manufacture of a multiple-reflection-type multilayer element is
      described that efficiently removes all wavelengths higher than 550 nm from the
      incident radiation and that at the same time acts as a polarizer in the 275-550
      nm spectral transmission region.

PMID- 12064406
TI  - Light-scattering measurements of optical thin-film components at 157 and 193 nm.
AB  - An instrument for total backscattering and forward-scattering measurements of
      optical coating components at 157 and 193 nm is described. The system is operated
      in both vacuum and nitrogen purge gas. An excimer laser as well as a deuterium
      lamp can be used as a radiation source. Suppression of the background signal
      level to 1 part in 10(6) permits measurements even of low-scatter samples such as
      superpolished substrates and antireflection coatings. Results of investigations
      of antireflective and highly reflective multilayers and CaF2 substrates reveal
      scattering from surface and interface roughness as well as from the volume of the
      substrate material. First steps to extend the instrument for angle-resolved
      scatter, transmittance, and reflectance measurements are described.

PMID- 12064407
TI  - High-performance deep-ultraviolet optics for free-electron lasers.
AB  - Working with wavelengths shorter than the deep ultraviolet involves the
      development of dedicated optics for free-electron lasers with devoted coating
      techniques and characterizations. High-performance deep-ultraviolet optics are
      specially developed to create low-loss, high-reflectivity dielectric mirrors with
      long lifetimes in harsh synchrotron radiation environments. In February 2001,
      lasing at 189.7 nm, the shortest wavelength obtained so far with free-electron
      laser oscillators, was obtained at the European Free-electron-laser project at
      ELETTRA Synchrotron Light Laboratory, Trieste, Italy. In July 2001, 330-mW
      extracted power at 250 nm was measured with optimized transmission mirrors.
      Research and development of coatings correlated to lasing performance are
      reported.

PMID- 12064408
TI  - Development of optical coatings for 157-nm lithography. I. Coating materials.
AB  - In a basic study to identify low-loss optics for applications in F2 lithography,
      five potential coating materials (AlF3, Na3AlF6, MgF2, LaF8, and GdF3) and three
      deposition methods (thermal evaporation by a resistance heater and by electron
      beam and ion-beam sputtering) were investigated in the vacuum ultraviolet (VUV)
      region. Samples were supplied as single-layer coatings on CaF2 substrates by four
      Japanese coating suppliers. Refractive indices (n) and extinction coefficients
      (k) of these coatings at 157 nm were evaluated; the transmittance and the
      reflectance were measured by a VUV spectrometer and were compared. As a result,
      resistance heating thermal evaporation is seen to be the optimal method for
      achieving low-loss antireflection coatings. The relation among optical constants,
      microstructures, and stoichiometry is discussed.

PMID- 12064409
TI  - Development of optical coatings for 157-nm lithography. II. Reflectance,
      absorption, and scatter measurement.
AB  - The total loss that can be suffered by an antireflection (AR) coating consists of
      reflectance loss, absorption loss, and scatter loss. To separate these losses we
      developed a calorimetric absorption measurement apparatus and an ellipsoidal
      Coblentz hemisphere based scatterometer for 157-nm optics. Reflectance,
      absorption, and scatter of AR coatings were measured with these apparatuses. The
      AR coating samples were supplied by Japanese vendors. Each AR coating as supplied
      was coated with the vendor's coating design by that vendor's coating process. Our
      measurement apparatuses, methods, and results for these AR coatings are presented
      here.

PMID- 12064410
TI  - High-reflectivity HfO2/SiO2 ultraviolet mirrors.
AB  - High-reflectivity dense multilayer coatings were produced for the ultraviolet
      spectral region. Thin-film single layers and UV mirrors were deposited by ion
      plating and plasma ion-assisted deposition high-energetic technologies. Optical
      characterizations of HfO2 and SiO2 single layers are made. The optical constants
      obtained for these two materials are presented. HfO2 and SiO2 mirrors with a
      reflectance of approximately 99% near 250 nm are reported.

PMID- 12064411
TI  - Atomic-precision multilayer coating of the first set of optics for an extreme
      ultraviolet lithography prototype system.
AB  - We present our results of coating a first set of optical elements for an extreme
      ultraviolet (EUV) lithography system. The optics were coated with Mo-Si
      multilayer mirrors by dc magnetron sputtering and characterized by synchrotron
      radiation. Near-normal incidence reflectances above 65% were achieved at 13.35
      nm. The run-to-run reproducibility of the reflectance peak wavelength was
      maintained to within 0.4%, and the thickness uniformity (or gradient) was
      controlled to within +/-0.05% peak to valley, exceeding the prescribed
      specification. The deposition technique used for this study is an enabling
      technology for EUV lithography, making it possible to fabricate multilayer-coated
      optics to accuracies commensurate with atomic dimensions.

PMID- 12064412
TI  - Piezoelectric tantalum pentoxide studied for optical tunable applications.
AB  - Piezoelectric transparent thin films are of great interest for use in tunable
      filters. We present experimental results on Ta2O5 single layers coated on fused
      silica substrates with an electron-beam deposition process. Above 450 degrees C,
      coatings change from an amorphous to a polycrystallized structure. When this
      structure shows a preferred orientation matching the piezoelectric tensor of the
      Ta2O5 crystal and the external electric field, variation in the piezoelectric
      layer thickness is expected. We detail experimental results in terms of optical
      (spectrophotometric and scattering measurements) and nonoptical characterizations
      (x-ray diffraction and scanning electron microscopy). Then the resultant
      thickness variation under oscillating applied voltage is measured with an
      extrinsic Fabry-Perot interferometer setup.

PMID- 12064413
TI  - Toward tunable thin-film filters for wavelength division multiplexing
      applications.
AB  - We provide a detailed analysis of the various problems connected with the
      development of tunable thin-film filters for wavelength-division multiplexing
      applications. We examine the relation between the change in layer thickness and
      the central wavelength shift for various configurations and point out the
      significance of the structure of the reflectors, the spacer thickness, and the
      location of the active layers. We describe and compare practical arrangements
      using either temperature or an electric field as the driving parameter.

PMID- 12064414
TI  - Thermally invariant dielectric coatings for micromirrors.
AB  - Thermal expansion-induced curvature becomes a major effect in micromirrors as the
      mirror diameter exceeds 100 microm. Such mirrors are used for optical switching,
      scanning, and many other applications. By using multilayer coatings instead of a
      single metal reflector, one can use the mechanical properties of the multilayer
      to create mirrors with zero curvature across temperature. We demonstrate the
      fabrication of such thermally invariant mirrors using dielectric coatings. A
      semianalytic model based on free-plate elastic theory is developed that uses
      empirical parameters in place of the true thermal expansion coefficients of the
      coating materials. Micromirrors are demonstrated that maintain their design
      curvature to within lambda/60 for lambda = 633 nm across an operating range from
      21 degrees C to 58 degrees C.

PMID- 12064415
TI  - Optical coatings with enhanced roughness for ultrahydrophobic, low-scatter
      applications.
AB  - Optical coatings with enhanced roughness offer promising prospects for
      ultrahydrophobic transparent surfaces with controlled scatter losses. Our
      approach links roughness characteristics with both wetting behavior and
      scattering. Experiments with rough oxide layers yielded surfaces with a high
      water contact angle.

PMID- 12064416
TI  - Overcoated microspheres for specific optical powders.
AB  - We produce overcoated microspheres and try to obtain artificial optical powders
      with specific spectral properties. Electron-beam deposition is used with a
      particular vibration system. Calibration and characterization results are
      presented that validate the techniques and procedures for single-layers and
      quarter-wave mirrors.

PMID- 12064417
TI  - Black layer coatings for the photolithographic manufacture of diffraction
      gratings.
AB  - A black layer coating for an aluminum-photoresist interface with a reflectance
      less than 0.1% for 413-nm, s-polarized light incident at 25 degrees is described.
      It is made of space-compatible materials, and its rms roughness is less than 15
      A.

PMID- 12064418
TI  - Control of resonant wavelength from organic light-emitting materials by use of a
      Fabry-Perot microcavity structure.
AB  - We report the fabrication of Fabry-Perot microcavity structures with the organic
      light-emitting material tris-(8-hydroxyquinoline) aluminum (Alq3) and derive
      their optical properties by measuring their photoluminescence (PL) and
      absorption. Silver and a TiO2-SiO2 multilayer were used as metal and dielectric
      reflectors, respectively, in a Fabry-Perot microcavity structure. Three types of
      microcavity were prepared: type A consisted of [air[Ag[Alq3]Ag]glass]; type B, of
      [air[dielectric[Alq3]dielectric]glass]; and type C, of
      [air[Ag[Alq2]dielectric]glass]. A bare Alq3 film of [air[Alq3]glass] had its PL
      peak near 514 nm, and its full width at half-maximum (FWHM) was 80 nm. The broad
      FWHM of a bare Alq3 film was reduced to 15-27.5, 7-10.5, and 16-16.6 nm for
      microcavity types A, B, and C, respectively. Also, we could control the PL peak
      of the microcavity structure by changing the spacer thickness, the amount of
      phase change on reflection, and the angle of incidence.

PMID- 12064419
TI  - Multilayer coatings on glass for painting protection and optimized color
      rendering.
AB  - Optical coatings offer a solution to the problem of damage to paintings, caused
      by ultraviolet and infrared radiation, by cutting radiation wavelengths outside
      the visible range. Simultaneously, these coatings can enhance an observer's
      viewing of the paintings by reducing the reflections from ordinary glass panes.
      All these functions should be performed by the same coating. The design of such a
      coating, as well as the evaluation of existing products, requires the definition
      of an appropriate merit function in which coating absorption, high transparency,
      and color rendering are combined.

PMID- 12064420
TI  - Calculated photonic structures for infrared emittance control.
AB  - Using an available program package based on the transfer-matrix method, we
      calculated the photonic band structure for two different structures: a quasi
      three-dimensional crystal of square air rods in a high-index matrix and an opal
      structure of high-index spheres in a matrix of low index, epsilon = 1.5. The high
      index used is representative of gallium arsenide in the thermal infrared range.
      The geometric parameters of the rod dimension, sphere radius, and lattice
      constants were chosen to give total reflectance for normal incidence, i.e.,
      minimum thermal emittance, in either one of the two infrared atmospheric windows.
      For these four photonic crystals, the bulk reflectance spectra and the wavelength
      averaged thermal emittance as a function of crystal thickness were calculated.
      The results reveal that potentially useful thermal signature suppression is
      obtained for crystals as thin as 20-50 microm, i.e., comparable with that of a
      paint layer.

PMID- 12064421
TI  - Artificial anisotropy and polarizing filters.
AB  - The calculated spectral transmittance of a multilayer laser mirror is used to
      determine the effective index of the single layer equivalent to the multilayer
      stack. We measure the artificial anisotropy of photoresist thin films whose
      structure is a one-dimensional, subwavelength grating obtained from interference
      fringes. The limitation of the theory of the first-order effective index
      homogenization is discussed. We designed normal-incidence, polarizing coating and
      a polarization rotator by embedding anisotropic films in simple multilayer
      structures.

PMID- 12064422
TI  - Parallel fluorescence detection of single biomolecules in microarrays by a
      diffractive-optical-designed 2 x 2 fan-out element.
AB  - We have developed a multifocal diffractive-optical fluorescence correlation
      spectroscopy system for parallel excitation and detection of single
      tetramethylrhodamine biomolecules in microarrays. Multifocal excitation was made
      possible through the use of a 2 x 2 fan-out diffractive-optical element with
      uniform intensity in all foci. Characterization of the 2 x 2 fan-out diffractive
      optical element shows formation of almost perfect Gaussian foci of submicrometer
      lateral diameter, as analyzed by thermal motion of tetramethylrhodamine dye
      molecules in solution. Results of parallel excitation and detection in a high
      density microarray of circular wells show single-biomolecule sensitivity in all
      four foci simultaneously.

PMID- 12064423
TI  - Electrical modulation of diffractive structures.
AB  - We present an experimental demonstration of two new methods for electronically
      modulating diffractive structures. The first involves the creation of periodic
      displacement of a liquid-air interface by application of a spatially modulated
      electric field produced by an array of electrodes. The second method also uses an
      electrode array but creates a diffraction grating by selectively attracting and
      repelling electrophoretic particles in a dielectric fluid. Potential areas of
      application of these techniques include controllable holography and wavelength
      division multiplexing.

PMID- 12064424
TI  - Closed-loop phase stepping in a calibrated fiber-optic fringe projector for shape
      measurement.
AB  - Active homodyne feedback control can be used to stabilize an interferometer
      against unwanted phase drifts introduced by, for example, temperature gradients.
      The technique is commonly used in fiber-optic sensors to maintain the fiber at
      its most sensitive (quadrature) position. We describe an extension of the
      technique to introduce stabilized, pi/2-rad phase steps in a full-field
      interferometer. The technique was implemented in a single-mode, fiber-optic
      interference fringe projector used for shape measurement and can be easily
      applied to other fiber- or bulk-optic interferometers, for example, speckle
      pattern and holographic interferometers. Fresnel reflections from the distal
      fiber ends undergo a double pass in the fibers and interfere at the fourth port
      of a directional coupler. The interference intensity (and hence phase) is
      maintained at quadrature by feedback control to a phase modulator in one of the
      fiber arms. Stepping between quadrature positions (separated by pi rad for light
      undergoing a double pass) introduces stabilized phase steps in the projected
      fringes (separated by pi/2 rad for a single pass). A root-mean-square phase
      stability of 0.61 mrad in a 50-Hz bandwidth and phase step accuracy of 1.17 mrad
      were measured.

PMID- 12064425
TI  - Silicone microlenses and interference gratings.
AB  - Interference gratings, plano-convex microlenses, and spherical microlenses have
      been made in silicone. Lenses were fabricated by the melting method. Two
      substrates have been tried: glass and Teflon. The latter substrate lets us
      fabricate low-f-number lenses. We made spherical microlenses by placing pieces of
      silicone near a thermal source and studied resolution of the lenses by
      investigating the images they gave of a test chart. We made low-spatial-frequency
      gratings by recording interference patterns and studied parameters involved in
      the recording. A study of the profile of the gratings and lenses was done with a
      mechanical surface analyzer.

PMID- 12064426
TI  - Angle-resolved ellipsometry of light scattering: discrimination of surface and
      bulk effects in substrates and optical coatings.
AB  - Angle-resolved ellipsometry of light scattering is an original technique
      developed at the Fresnel Institute to identify scattering processes in substrates
      and multilayers. We extend the investigation because numerous experimental
      results proved that the technique can be of major interest for analysis of
      microcomponents and their scattering origins. Surface and bulk effects can be
      separated in most situations, as well as the oblique growth of materials and the
      presence of first-order contaminants.

PMID- 12064427
TI  - A comparison of drinking patterns and alcohol-use-related problems in the United
      States and Germany, 1995.
AB  - Distinct drinking habits are seen in the United States and Germany. Using 1995
      national surveys, we examined alcohol consumption patterns, demographic
      correlates, and relationships between consumption and problems. Although
      differing in design (Germany: mail survey; United States: face-to-face
      interviews), both surveys shared measures that permitted comparisons. Drinking
      volume and pattern were assessed and the CAGE screening test for alcohol-use
      related problems was used. Germany has larger prevalence of current drinking,
      higher levels of consumption, and more heavy drinkers. However, at matched volume
      levels, more Americans reported alcohol-use-related problems. Sociodemographic
      correlates of heavier consumption also varied between countries. Results support
      the role of cultural traditions in the expression and recognition of alcohol-use
      related problems.

PMID- 12064429
TI  - The role of aggression-related alcohol expectancies in explaining the link
      between alcohol and violent behavior.
AB  - Studies have demonstrated an acute effect of alcohol on violent behavior. A
      remaining issue is the motivation of some offenders for using alcohol before
      offending. A common explanation is based on the relationship between daily
      drinking habit and drinking before offending. Drawing upon the deviance disavowal
      assumption, the embolden hypothesis, and expectancy theories, the present study
      argues that alcohol may be used intentionally to promote or excuse the violent
      consequences of drinking. Using data from the 1993 Buffalo Longitudinal Study of
      Young Men, the present study examines the independent effect of aggression
      related alcohol expectancies on drinking before offending and the interactive
      effect of aggression-related alcohol expectancies and daily alcohol consumption
      on drinking before offending. The results indicate a significant effect of
      aggression-related alcohol expectancies on alcohol use before offending. This
      supports the argument that drinking may be a means for carrying out violent acts.
      A significant interactive effect was found between aggression-related alcohol
      expectancies and daily alcohol consumption. "Heavy" daily alcohol consumption
      increased the likelihood of drinking before offending for individuals who had
      high aggression-related alcohol expectancies more than those who had low such
      expectancies. Aggression-related alcohol expectancies moderated the effect of
      daily drinking on drinking before offending. The implications of these findings
      are discussed for the link between alcohol and violence.

PMID- 12064428
TI  - Acculturation and Latino adolescents' substance use: a research agenda for the
      future.
AB  - This paper conducts a review of the literature on acculturation by Latino
      adolescents to traditional European-American cultural values and its effect on
      their substance-using behaviors. This review includes a critical analysis of
      studies that examine the effects of acculturation on the mental wellbeing of
      Latino adolescents. Recent findings documenting the association between
      acculturation and substance use among Latino adolescents are discussed. This
      paper also examines the limitations of the current research and proposes the
      development of acculturation scales that focus on measuring the role that
      predominant Latino and American values, attitudes, and norms play in the
      substance-use behavior of Latino adolescents. Additionally, the author proposes
      the development of a conceptual framework that accounts for the impact of
      acculturation-related stress and the mitigating factors affecting such stress on
      the substance-use behavior of Latino adolescents. The author asserts that
      understanding the effects of acculturation-related stress and accompanying
      mitigating factors could begin to explain the increasingly high rates of
      substance use reported for Latino adolescents. There is a discussion of research
      gaps and related research issues, and recommendations for future research are
      also made.

PMID- 12064430
TI  - The relationship of childhood abuse history and substance use in an Alaska
      sample.
AB  - This study confirms a strong link between childhood abuse history and substance
      misuse based upon data obtained from an ethnically diverse (largely Alaska
      Native) sample of 192 pregnant women in substance misuse treatment in the mid
      1990s. Nearly three-quarters of the women reported childhood victimization.
      Compared to women with no abuse history, abused women were significantly younger
      at the age of onset of substance misuse, used substances more frequently, had
      experienced more blackouts, had more family members with substance-misuse
      concerns, were more likely to have been raped, revealed more psychological
      problems, and had less formal education. Risk patterns differed slightly for
      women with physical versus sexual abuse histories, with the experience of
      physical violence having a stronger relationship with adulthood problem behaviors
      than the experience of sexual molestation. Overall, findings suggest an
      interactive cycle of violence and substance misuse that begins very early in
      childhood, especially for women who were physically abused, and continues in
      adulthood, though no cause-end-effect conclusions can be drawn. Treatment and
      prevention implications of these findings are discussed.

PMID- 12064431
TI  - Canadian illicit opiate users' views on methadone and other opiate prescription
      treatment: an exploratory qualitative study.
AB  - Although methadone treatment has been available in North America for decades,
      only a small proportion of opiate addicts (some 25% of estimated opiate users in
      Canada) are receiving methadone treatment. Many users have tried methadone
      treatment, often multiple times, but leave treatment prematurely. Others would
      not consider it as a worthwhile treatment option for themselves. This exploratory
      study examines regular opiate users' attitudes towards and experiences with
      methadone treatment in Canada, primarily setting out to determine what makes
      methadone an unsuccessful or even an undesirable treatment option for
      considerably large groups of opiate users. This empirical effort to explore the
      limitations of existing methadone treatment comes at an appropriate time, when
      alternative forms of opiate pharmacotherapy treatment are being proposed in
      Canada as complementary modes of intervention that hope to address the
      shortcomings of methadone treatment. The rationale for this study were
      feasibility questions and development efforts for a clinical trial in North
      America evaluating the effectiveness of using injectable opioids (heroin,
      dilaudid) in attracting and engaging treatment-resistant opiate users into
      treatment. Data for this exploratory qualitative study was collected in 1999
      through a series of focus groups involving 47 treatment-experienced and treatment
      naive opiate users in Vancouver, Montreal, and Toronto, with the objective of
      identifying key themes and issues on the described topic as a basis for further
      systematic research.

PMID- 12064432
TI  - Methadone and heroin prescription: babies and bath water.
AB  - Criticism of methadone treatment abounds in all countries where this intervention
      is available. Although such criticism is often justified, it is critical to
      recognize that methadone is the most effective, safe, and cost-effective
      intervention available, is supported by innumerable studies, and provides
      considerable benefit to drug users, their families and communities. The major
      causes of the pervasive deficiencies of methadone treatment is the severe and
      consistent under-funding and hostile environment, both inevitable by-products of
      the global commitment over recent decades to an expensive, ineffective, and often
      counter-productive drug policy overly reliant on supply reduction. Methadone
      treatment is often criticized by drug war supporters not because of its
      limitations, but because its very effectiveness highlights the meagre benefits of
      supply reduction. The compelling arguments to expand pharmacotherapies for heroin
      dependence by rigorously evaluating prescription heroin treatment should not be
      based on the real or perceived deficiencies of methadone treatment. Rather, these
      arguments should be based on the need to provide evidence-based treatment for
      drug users which has the capacity, range of options, and quality expected in
      other health care services. The paramount aim should be to improve the current
      deplorable rates of death, disease, crime, and severe distress now evident in an
      increasing number of countries.

PMID- 12064433
TI  - The role of consumers. Reflection on the possibilities and limits of user
      interviews in opiate addiction treatment.

PMID- 12064434
TI  - The search for a comprehensive strategy toward opiate addiction.

PMID- 12064435
TI  - Whose needs are to be met? Customer satisfaction with delivery of treatment
      services for heroin users.

PMID- 12064436
TI  - Heroin maintenance and the United States.

PMID- 12064437
TI  - The effectiveness of the medical prescription of heroin studied by randomized
      trials in The Netherlands, watched suspiciously by parliament and neighborhoods.

PMID- 12064438
TI  - Appreciating the user's perspective: listening to the "methadonians".
AB  - Researchers have long neglected the user's perspective and experiences in
      assessing drug effects and drug use. With increased interest in Canada directed
      at prescribing heroin in place of methadone, researchers took the relatively
      unique approach of gathering data and information from methadone users to
      determine their views and experiences with methadone programs and alternative
      treatment choices. The results of that research portrayed very interesting and
      useful notions of users regarding methadone maintenance and the prescribing of
      heroin.

PMID- 12064439
TI  - Poppy seeds and opiate concentration in urine.

PMID- 12064440
TI  - Transmission of hepatitis C--are noninjecting cocaine users at risk?

PMID- 12064441
TI  - Hsp70 as a stress marker of sea urchin coelomocytes in short term cultures.
AB  - Coelomocytes are the immune effectors of the sea urchin and have shown to respond
      to environmental and experimental challenge by the activation of stress markers.
      We extended our in vivo studies to in vitro short term cultures of sea urchin
      coelomocytes by analysing their response to temperature being stress, acid pH and
      heavy metals, using the hsp70 protein as a stress marker. We found that the in
      vitro time course of temperature stress recapitulates results obtained in vivo
      where the highest overexpression was observed after 1 hour. Coelomocytes
      overexpress hsp70 in a time-dependent manner when cultured for 1 to 6 hr at pH
      4.7 +/- 0.2 in isotonic buffer, supplemented with EDTA as anticoagulant. A peak
      in the level of hsp70 expression was observed at 2 hr of culture, corresponding
      to a 10-fold increase over the levels of control coelomocytes cultured at pH 7.3
      +/- 0.2. The effect of different concentrations of CdCl2 in the culture over a
      period of 4 hr was also tested. We found that CdCl2 greatly increases the hsp70
      expression, with 10(-3) M the dose at which the highest overexpression is
      observed.

PMID- 12064442
TI  - Cell culture of bivalves: tool for the study of the effects of environmental
      stressors.
AB  - Spontaneous beating cells can be isolated from the heart of the oyster
      (Crassostrea gigas) and cultured for more than two months. They form adherent
      contractile networks in culture conditions. They show muscarinic and beta
      adrenergic reactivity thus showing that they are functional cardio-myocytes:
      Acetylcholine induced a dose dependent decrease in spontaneous beating rate via
      an increase in potassium conductance, this effect being blocked by atropine.
      Epinephrine induced a dramatic increase in calcium conductance which was blocked
      by high concentrations of propranolol but not by sotalol and reversed by
      verapamil. Tributyltin and cadmium induced a dose and time dependent decrease
      mainly in inward ionic conductances, leading to a decrease or even a total
      suppression of the beating rate. Present study indicates that this model could be
      used as a sensitive test to study the effects of some marine pollutants at the
      cellular level in molluscs.

PMID- 12064444
TI  - Application of alkaline elution, Fast Micromethod and flow cytometry in detection
      of marine contamination.
AB  - DNA damage is an inescapable aspect of life in the biosphere. The presented
      investigations were an attempt to examine the response of a DNA damage as a
      biomarker of environmental quality in the mussels Mytilus galloprovincialis
      sampled at differently contaminated areas of Istrian coast, Northern Adriatic.
      The investigations were performed in order to get information about the genotoxic
      risk for marine organisms exposed to mixed environmental pollution, as well as
      the information about the presence of unknown mixture of genotoxic contaminants
      in the marine environment. Types of DNA damage detected are alkali-labile sites
      and single-strand breaks measured by Fast Micromethod, interstrand cross-links
      and DNA protein cross-links by alkaline filter elution and cell cycle
      disturbation by flow cytometry. The applicability of all three methods for marine
      quality control is discussed.

PMID- 12064443
TI  - Lake Baikal: a unique place to study evolution of sponges and their stress
      response in an environment nearly unimpaired by anthropogenic perturbation.
AB  - Lake Baikal is considered as a unique place to study evolution. In this review,
      we report on recent data on the evolution of endemic freshwater sponges of this
      ancient lake. Nucleotide sequence data support the idea that these sponges are of
      monophyletic origin and evolved from Spongillidae. Baikalian sponges form the
      dominating biomass in the benthos of the lake. Data on the expression of the
      biomarker heat shock protein 70, revealed that the endemic sponge species of Lake
      Baikal are useful as bioindicators to assess the anthropogenic impact on the
      lake.

PMID- 12064445
TI  - Heat-stable protease from the marine sponge Geodia cydonium.
AB  - A protease from the marine sponge Geodia cydonium was purified from an aqueous
      extract by gel filtration and anion-exchange chromatography. A 200-kDa
      proteolytically active band was obtained when the enzyme was analyzed in gelatin
      copolymerized zymograms. The enzyme was also able to degrade casein, bovine
      collagen, and the synthetic substrate alpha-N-benzoyl-D-arginine p-nitroanilide
      (BAPNA). Optimal conditions for proteolytic activity were achieved in the
      presence of 10 mM CaCl2 and within the pH range 7.0 to 8.5. The protease showed
      an extraordinary heat resistance. The enzyme activity was inhibited by
      phenylmethylsulphonyl fluoride (PMSF) and N-tosyl-lysine chloromethyl ketone
      (TLCK), suggesting that the enzyme belongs to the group of serine-type proteases.
      We propose that the protease is involved in sponge collagen catabolism.

PMID- 12064446
TI  - Measurement of DNA damage induced by irradiation with gamma-rays from a TRIGA
      Mark II research reactor in human cells using Fast Micromethod.
AB  - The Fast Micromethod is a novel quick and convenient microplate assay for
      determination of DNA single-strand breaks. This method measures the rate of
      unwinding of cellular DNA upon exposure to alkaline conditions using a
      fluorescent dye which preferentially binds to double-stranded DNA. Here we
      applied this method to determine the levels of DNA single-strand breaks in HeLa
      cells induced by y-irradiation deriving from fission isotopes and activation
      products at the TRIGA Mark II research reactor in Mainz. An increased strand
      scission factor (SSF) value, which is indicative for DNA damage, was found at
      doses of 1 Gy and higher. A similar increase in SSF value, which further
      increased in a dose-dependent manner, was found in human peripheral blood
      mononuclear cells after irradiation with 6 MV X-rays from a linear accelerator to
      give a total exposure of 0.5 to 10 Gy.

PMID- 12064447
TI  - Long-term effects of low-dose irradiation on human health.
AB  - The effects caused by low-dose irradiation differ from those caused by high-dose
      irradiation. At present only little is known about the long-term effects of
      chronical exposure of individuals and whole populations to low-dose irradiation.
      This problem particularly concerns people living in territories heavily
      contaminated with radioactive material due to Chernobyl Nuclear Power Plant
      accident. We investigated different parameters of the peripheral blood from 124
      men, working at the "Shelter" object (demolished block IV of the nuclear power
      plant). In many cases the accumulated radiation dose (gamma-rays) was more than
      50 rem. As control group we examinated 302 male donors (of the same age) from the
      Kiev blood-transfusion station. The studies revealed the following effects in the
      "Shelter" object workers: an increased manifestation of signs of common
      inflammatory reactions, such as an increased number of leukocytes and absolute
      number of white blood cells, an unproportionally high number of monocytes and
      band neutrophiles, and an increase in plasma cytokine levels (interferon-alpha,
      tumor necrosis factor-beta but not interleukin-1beta). Ongoing studies are
      targeted to develop and introduce new methods and techniques to measure the
      frequency of DNA strand breaks in peripheral blood lymphocytes for the
      surveillance of persons working and/or living in a radioactively contaminated
      environment after Chemobyl accident.

PMID- 12064448
TI  - Genetic instability in peripheral blood lymphocytes of Chernobyl clean-up
      workers.
AB  - The group of clean-up workers involved in the liquidation of the consequences of
      the major accident at the Chemobyl nuclear power plant (CNPP) was exposed to high
      doses of radiation. In this review, we summarize the results of a long-term study
      of the cytogenetic status of CNPP clean-up workers. The data revealed different
      trends of the parameters of the cytogenetic status in the course of the study.
      The results of biological dose reconstruction, based on the frequency of mutant T
      helper cells, are discussed.

PMID- 12064450
TI  - Congenital malformations among newborns and developmental abnormalities among
      human embryos in Belarus after Chernobyl accident.
AB  - Evaluation of the effects of radioactive contamination on human populations is
      important for an understanding of the present and future risk for human health,
      including the genetic risk. This review centers on the results of population
      monitoring of developmental anomalies among human embryos and congenital
      malformations among newborn in the Republic of Belarus before and after Chemobyl
      accident. The data revealed that the incidences of developmental anomalies and
      congenital malformation from the mostly radionuclide-contaminated rural regions
      of Belarus reliably exceed the indices in control areas.

PMID- 12064449
TI  - Neurotransmitter receptor expression by peripheral mononuclear cells: possible
      marker of neuronal damage by exposure to radiations.
AB  - Peripheral mononuclear cells (PMC) express several neurotransmitter systems.
      Increasing evidence suggests that PMC neurotransmitter receptors are involved in
      modulating immune responses. It is also thought that expression of PMC
      neurotransmitter receptors may reflect the status of homologous brain receptors.
      A problem encountered with assay of PMC neurotransmitter receptors was in
      developing techniques suitable for their assessment in spite of low density. In
      this paper we summarized findings on the expression of alpha1-adrenoceptor and
      dopamine receptor subtypes in human peripheral blood lymphocytes characterized by
      radioligand binding assay techniques and immunocytochemistry. Human lymphocytes
      express alpha1A-, alpha1B- and alpha1D-adrenoceptor subtypes and dopamine D3, D4
      and D5 receptors. Compared to radioligand binding assay, immunocytochemistry
      applied to cytospin-centrifuged peripheral lymphocytes allowed to assay receptor
      subtypes investigated in small amounts of blood. The development of sensitive and
      reproducible techniques for assaying PMC neurotransmitter receptor subtypes even
      in small amounts of blood such as those used for diagnostic purposes may allow to
      analyze their sensitivity to different conditions including radiation exposure.

PMID- 12064451
TI  - Outbreak of acute gastroenteritis associated with Norwalk-like viruses among
      British military personnel--Afghanistan, May 2002.
AB  - In the United States, Norwalk-like viruses (NLVs) cause an estimated 23 million
      episodes of illness, 50,000 hospitalizations, and 300 deaths each year. NLVs can
      be transmitted by fecally contaminated food and water and by direct person-to
      person contact or through droplets of infected persons. Outbreaks of NLV
      associated gastrointestinal illness are common in military settings. During May
      13-19, 2002, a total of 29 British soldiers and staff of a field hospital in
      Afghanistan became acutely ill after a short incubation period with vomiting,
      diarrhea, and fever. This report summarizes the investigation of this outbreak
      and underscores the importance of the diagnostic capacity for NLVs.

PMID- 12064452
TI  - Progress toward poliomyelitis eradication--Nigeria, January 2000-March 2002.
AB  - Since 1988, when the World Health Assembly of the World Health Organization (WHO)
      resolved to eradicate poliomyelitis globally, the annual estimated incidence of
      polio has declined 99%. Nigeria is the most populous country in Africa (estimated
      2000 population: 127 million) and a major poliovirus reservoir. This report
      summarizes the progress toward polio eradication in Nigeria during January 2000
      March 2002, highlighting achievements in acute flaccid paralysis (AFP)
      surveillance and evidence indicating reduced poliovirus transmission. The
      findings underscore the importance of ensuring a rapid flow of surveillance
      information to guide program activities.

PMID- 12064453
TI  - Rabies in a beaver--Florida, 2001.
AB  - On November 25, 2001, a beaver exhibited aggressive behavior by charging canoes
      and kayaks on the Ichetucknee River in Alachua County, Florida. The beaver was
      captured by park personnel and submitted to a Florida Department of Health (FDoH)
      laboratory for rabies testing. Park rangers contacted the Alachua County Health
      Department after they identified five persons who were in the vicinity of the
      animal before capture. These five persons were interviewed by county health
      department personnel, who reported that although the beaver had made aggressive
      actions, the animal had not bitten anyone. This report summarizes the
      investigation of this case of animal rabies. Mammals that exhibit aggressive or
      other unusual behavior should be reported promptly to local health officials and
      should not be approached or handled by the public.

PMID- 12064454
TI  - Update: Cutaneous anthrax in a laboratory worker--Texas, 2002.
AB  - On April 5, 2002, CDC reported a case of suspected cutaneous anthrax in a worker
      at laboratory A who had been processing environmental samples for Bacillus
      anthracis in support of CDC investigations of the 2001 bioterrorist attacks in
      the United States. Since the initial report, the worker had serial serology
      performed at the CDC laboratory. A greater than fourfold rise from baseline in
      the concentration of immunoglobulin G to protective antigen was demonstrated. The
      peak antibody level was observed 7-8 weeks after the onset of symptoms, and the
      time course and levels of detectable antibodies were consistent with those seen
      in other cases of cutaneous anthrax. On the basis of case definitions developed
      during the recent investigation, these additional findings confirm this as a case
      of cutaneous anthrax. This case brings the number of anthrax cases identified in
      the United States since October 3, 2001, to 23, including 11 inhalation and 12
      cutaneous (eight confirmed and four suspected). This is the first laboratory
      acquired case of anthrax associated with the recent investigation.

PMID- 12064455
TI  - Distinct physiological roles of the Gq-coupled metabotropic glutamate receptors
      Co-expressed in the same neuronal populations.
AB  - The group I metabotropic glutamate receptors, mGluR1 and mGluR5, exhibit a high
      degree of sequence homology, and are often found co-expressed in the same
      neuronal populations. These receptors couple to a broad array of effector
      systems, and are implicated in diverse physiological and pathophysiological
      functions. Due to the high degree of sequence homology, and the findings that
      these receptors couple identically in recombinant systems, it has been generally
      assumed that these two group I mGluR subtypes would exhibit redundant function
      when coexpressed in the same neurons. With the advent of subtype-selective
      pharmacological tools, it has become possible to tease apart the functions of
      mGluR1 and mGluR5 in the same neuron. The emerging picture is one of diverse
      function, which implies differential regulation. Interestingly, the group I
      mGluRs are modulated by a rich variety of regulatory systems, which may explain
      how these receptors can mediate divergent actions when present in the same cell.

PMID- 12064456
TI  - Functional analysis of mouse hepatocytes differing in DNA content: volume,
      receptor expression, and effect of IFNgamma.
AB  - Polyploidy and binuclearity are characteristics of the mammalian liver.
      Increasing polyploidisation occurs with age and after administration of various
      drugs and chemicals. This study was designed to examine the function of ploidy by
      addressing several questions: (1) Does the increase in size of polyploid
      hepatocytes have any physiological function by altering surface receptor
      expression such as intercellular adhesion molecule-1 (ICAM-1, CD54) or IFNgammaR?
      and (2) Do polyploid cells respond differently to inflammatory cytokines such as
      interferon gamma (IFNgamma)? We have developed a method to accurately measure the
      volume of live isolated hepatocytes using confocal microscopy and image analysis.
      Using flow cytometry, we have shown that the expression of ICAM-1 increases with
      increasing DNA content and IFNgammaR is not detectable on isolated mouse
      hepatocytes. Diploid (2n), tetraploid (4n) and octoploid (8n) hepatocytes were
      found to be equally susceptible to IFNgamma-induced apoptosis in vitro. Although
      the function of polyploidy remains unanswered, we have described some of the
      characteristics of polyploidy in isolated hepatocytes and in vitro.

PMID- 12064457
TI  - P2P-R protein localizes to the nucleolus of interphase cells and the periphery of
      chromosomes in mitotic cells which show maximum P2P-R immunoreactivity.
AB  - P2P-R is a nuclear protein that can bind both p53 and Rb1. Its functions include
      roles in the control of RNA metabolism, apoptosis, and p53-dependent
      transcription. The expression of P2P-R also is repressed in G1 arrested
      terminally differentiated cells. The current studies therefore evaluated if P2P-R
      undergoes cell cycle-associated changes in its abundance and/or localization.
      Western blots show that relative to G0 quiescent cells, P2P-R protein levels are
      higher in populations of G2/M cells prepared by the physiological
      parasynchronization technique of serum deprivation followed by serum stimulation.
      More striking is the > 10-fold enrichment of P2P-R protein in specimens of highly
      purified mitotic cells prepared by the mitotic shake-select technique, or by
      synchrony with the mitotic spindle disruption agents nocodazole or vinblastine.
      These changes in P2P-R protein occur without a concomitant change in P2P-R mRNA
      expression suggesting that P2P-R immunoreactivity increases during mitosis.
      Confocal microscopy next established the localization of P2P-R to nucleoli in
      interphase cells and at the periphery of chromosomes in mitotic cells that lack
      nucleoli. The high levels of P2P-R localized to the periphery of chromosomes in
      mitotic cells suggest that P2P-R shares characteristics with other nucleolar
      proteins that associate with the periphery of chromosomes during mitosis. These
      include: nucleolin, B23, Ki67, and fibrillarin.

PMID- 12064458
TI  - Effect of pre-adsorbed proteins on attachment, proliferation, and function of
      endothelial cells.
AB  - As certain proteins control cell adhesion, it has been hoped that cell
      transplantation and tissue engineering could be augmented by pre-adsorption of
      specific proteins to biological or synthetic surfaces. The questions that remain,
      however, are whether such proteins can affect cell production as well as
      adhesion, and if so, whether in a protein-specific manner. We examined the
      adhesion and the biochemical secretion of bovine aortic endothelial cells (BAEC)
      on tissue culture polystyrene (TCPS) discs coated with fibronectin (Fn), laminin
      (Ln), or gelatin. The three coating proteins nonspecifically promote sub
      confluent and post-confluent endothelial cell production of total protein up to
      2.5-fold of the reference value. Total soluble glycosaminoglycan (GAG) production
      slightly increased with the different coatings only at low cell density. In
      contrast, Ln and Fn, not gelatin, drastically enhanced post-confluent BAEC
      production of prostaglandin (PGI2). However, antibody-blockage of the alpha5
      integrin, constituent of the Fn receptor in BAEC, appeared to inhibit the
      upregulation of PGI2 production observed on Fn-coated surfaces. The results
      indicate that the cell adhesion mediators used as coating agents dictate cell
      biological production as well as adhesion and proliferation.

PMID- 12064459
TI  - Stimulation of the proliferation and differentiation of mouse pink-eyed dilution
      epidermal melanocytes by excess tyrosine in serum-free primary culture.
AB  - The epidermal cell suspensions of the neonatal dorsal skin derived from wild type
      mouse at the pink-eyed dilution (p) locus (black, C57BL/10JHir-P/P) and their
      congenic mutant mouse (pink-eyed dilution, C57BL/10JHir-p/p) were cultured with a
      serum-free melanocyte growth medium supplemented with additional L-tyrosine (Tyr)
      from initiation of the primary culture. L-Tyr inhibited the proliferation of
      P/Pmelanocytes in a dose-dependent manner, whereas L-Tyr stimulated the
      proliferation of p/p melanoblasts and melanocytes regardless of dose. On the
      other hand, L-Tyr stimulated (P/P) or induced (p/p) the differentiation of
      epidermal melanocytes in a dose-dependent manner. In both P/P and p/p
      melanoblasts and melanocytes cultured with 2.0 mM L-Tyr for 14 days, slight
      increases in contents of eumelanin marker, pyrrole-2,3,5-tricarboxylic acid
      (PTCA) and pheomelanin marker, aminohydroxyphenylalanine (AHP) were observed. The
      average number of total melanosomes (stages I, II, III, and IV) per P/P
      melanocyte was not changed by L-Tyr treatment, but the proportion of stage IV
      melanosomes in the total melanosomes was increased. On the contrary, in p/p
      melanoblasts and melanocytes L-Tyr increased dramatically the number of stage II,
      III, and IV melanosomes as well as the proportion of stage III melanosomes.
      Contents of PTCA and eumelanin precursor, 5,6-dihydroxyindole-2-carboxylic acid
      (DHICA) of cultured media in p/p melanocytes were much more greatly increased
      than in P/P melanocytes. However, contents of AHP and pheomelanin precursor, 5-S
      cysteinyldopa (5-S-CD) of cultured media in p/p melanocytes were increased in a
      similar tendency to P/Pmelanocytes. These results suggest that p/p melanocytes in
      the primary culture are induced to synthesize eumelanin by excess L-Tyr, but
      difficult to accumulate them in melanosomes.

PMID- 12064460
TI  - Phosphorylation of pRb is required for HGF-induced muscle cell proliferation and
      is p27kip1-dependent.
AB  - Hepatocyte growth factor (HGF) plays a crucial role in the differentiation of
      skeletal muscle cells, where a process in which the retinoblastoma protein (pRb)
      has been implicated. We addressed the role of pRb in HGF-mediated effects on the
      proliferation and differentiation of adult skeletal muscle myoblasts. HGF shifted
      pRb to its hyperphosphorylation forms and increased the transactivation of E2F1,
      a transcription factor required for S phase entry. A constitutively active pRb
      mutant blocked HGF-dependent pRb phosphorylation and transactivation of E2F1 and
      increased cell proliferation. Accordingly, this mutant reversed the inhibitory
      effects of HGF on the expression of the cyclin-dependent kinase (CDK) inhibitor
      p27 and myogenic differentiation markers. HGF-mediated pRb phosphorylation was
      reversed by ectopic expression of p27, but neither the myogenic regulatory
      factor, MEF2, nor the myogenic inhibitory protein Twist had that effect. These
      results suggest that in response to HGF signaling, there is a decrease in p27
      expression that results in an accumulation of hyperphosphorylated Rb protein, and
      subsequent progression of myoblasts into the G1 phase of the cell cycle.

PMID- 12064461
TI  - New human myelodysplastic cell line, TER-3: G-CSF specific downregulation of
      Ca2+/calmodulin-dependent protein kinase IV.
AB  - We have established a new hematopoietic cell line from a patient with
      myelodysplastic syndrome (MDS), which was refractory anemia with excess blasts
      (RAEB). This cell line, designated TER-3, depends on several cytokines for long
      term survival and growth, and requires interleukin-3 (IL-3) for continuous
      growth. Cytochemical analysis revealed that TER-3 cells are weakly dianisidine
      positive and nonspecific esterase positive, but peroxidase negative. The surface
      marker profile shows that the TER-3 cells are strongly positive for myeloid,
      lymphoid, and megakaryocytic antigens such as CD15, CD19, and CD61, and negative
      for some common multilineage antigens such as CD13, CD33, and CD34. Thus, this
      cell line has a multilineage phenotype, suggesting that the transformation event
      occurred in multipotent stem cells. Dianisidine- and nonspecific esterase
      positive TER-3 cells increase with granulocyte-colony stimulating factor (G-CSF)
      rather than with IL-3. These results suggest that the cell line is useful for
      understanding the mechanism underlying G-CSF-associated hematopoietic cell
      differentiation and activation in the patient with MDS.

PMID- 12064462
TI  - Arachidonic acid release by cPLA2 may be causally related to NO-induced apoptosis
      in vascular smooth muscle cells.
AB  - Apoptosis has been shown to occur in vascular smooth muscle cells during the
      development of atherosclerosis. In order to investigate the possible role of
      arachidonic acid during apoptosis in vascular smooth muscle, we induced apoptosis
      in cultured rat aortal smooth muscle cells (SMCs) by treatment with either UV
      (ultraviolet) radiation, tumor necrosis factor-alpha (TNF-alpha) or NO donor
      drugs (sodium nitroprusside, or S-nitroso-N-acetyl-D-penicillamine, SNAP).
      Apoptosis was detected by either DNA fragmentation analysis or by TUNEL analysis.
      UV radiation, TNF-alpha and NO were observed to stimulate apoptosis in the cells
      as well as to stimulate arachidonate release from the cells. NO also increased
      levels of cPLA2 in the cells, which is an enzyme that is frequently activated in
      cells that release arachidonate. These agents stimulated arachidonate release
      somewhat earlier than they stimulated apoptosis in the cells. The inhibition of
      cPLA2 by arachidonyl trifluoromethyl ketone (AACOCF3) also led to the inhibition
      of arachidonate release from the cells as well as the inhibition of nitroprusside
      stimulated apoptosis. Arachidonic acid itself could induce apoptosis in the
      cultured cells. These observations provide evidence that arachidonate may be
      involved in apoptosis in vascular smooth muscle.

PMID- 12064463
TI  - Signaling of monocytic differentiation by a non-hypercalcemic analog of vitamin
      D3, 1,25(OH)2-5,6 trans-16-ene-vitamin D3, involves nuclear vitamin D receptor
      (nVDR) and non-nVDR-mediated pathways.
AB  - Exposure of leukemia cells to the physiologically active form of vitamin D3, 1,25
      dihydroxyvitamin D3 (1,25D3) normalizes their phenotype to cells that resemble
      mature monocytes. One of the earliest detectable events in this process is an
      upregulation of the nuclear receptor for 1,25D3, the vitamin D receptor (nVDR).
      In contrast, the novel analog of 1,25D3, 1,25-dihydroxy-5,6 trans-16-ene-vitamin
      D3 (5,6-16D3), which has recently been reported to have low calcium-mobilizing
      activity in vivo, rapidly induced the expression of CD14, CD11b, and monocyte
      specific esterase (MSE), classical markers of the mature monocyte, but
      upregulated nVDR expression less than 1,25D3. This upregulation was shown to be
      the result of altered degradation of the nVDR protein, while the levels of nVDR
      mRNA were constant. Knock-out of nVDR transcriptional activity by a decoy VDRE
      double-stranded deoxyoligonucleotide, markedly abrogated 1,25D3-induced
      differentiation, but incompletely inhibited 5,6-16D3-induced differentiation.
      These findings suggest that the unique ability of 5,6-16D3 to induce cell
      differentiation but not systemic hypercalcemia, may be due to the activation of
      pathways which initiate differentiation independently of nVDR.

PMID- 12064464
TI  - Expression of matrix metalloproteinase-2 and -9 and their inhibitors, tissue
      inhibitor of metalloproteinase-1 and -2, in primary cultures of human prostatic
      stromal and epithelial cells.
AB  - The production of matrix metalloproteinases (MMPs) by prostatic epithelial and/or
      neighboring stromal cells is considered to be a property that gives cells the
      capability to penetrate extracellular matrix barriers in normal or neoplastic
      growth. In order to examine the role of MMPs in the prostate, we evaluated the
      expression of MMP-2 and -9 and the tissue inhibitors of matrix metalloproteinases
      (TIMP)-1 and -2 in primary cultures of prostatic stromal and epithelial cells.
      These cells were isolated from normal tissues of the different zones of the
      prostate, from benign prostatic hyperplasia (BPH) and from cancer. Stromal cells,
      regardless of tissue of origin, secreted the 72-kDa proenzyme form of MMP-2,
      whereas conditioned media (CM) from epithelial cells demonstrated little/no pro
      MMP-2 as examined by zymography. Either type of cell did not secrete MMP-9. RT
      PCR evaluation showed stromal cells expressed transcripts for MMP-2, but not for
      MMP-9. Transcripts for MMP-9 were detected in epithelial cells, although no MMP-9
      activity was detected in their CM. Treatment of stromal cells with 1 or 10 ng/ml
      of transforming growth factor-beta (TGF-beta) moderately increased secretion of
      pro-MMP-2 protein with little change in MMP-2 RNA. However, treatment of
      epithelial cells with TGF-beta induced expression and secretion of both MMP-2 and
      9. The effect of TGF-beta on expression of MMPs by epithelial cells was not
      duplicated or affected by treatment with insulin-like growth factor (IGF)-1,
      epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or basic
      fibroblast growth factor (bFGF). Stromal cells expressed transcripts of both TIMP
      1 and -2. Epithelial cells expressed TIMP-1, but little TIMP-2. TGF-beta did not
      regulate the expression of TIMP-1 or -2 in either stromal or epithelial cells.
      Our results suggest that the elevated levels of MMP-2 and -9 observed in prostate
      development and cancer may be due to the elevated TGF-beta associated with these
      tissues.

PMID- 12064465
TI  - COX-dependent and -independent pathways in bradykinin-induced anion secretion in
      rat epididymis.
AB  - Lysylbradykinin (LBK) added to the apical or basolateral side of cultured rat
      epididymal monolayers stimulated a rise in short-circuit current (Isc) due to
      anion secretion. The concentration-response relationships for the apical and
      basolateral applications have EC50 value of 0.001 microM. The responses to apical
      or basolateral application of LBK were blocked by WIN64338, a specific B2
      receptor antagonist, but not by Des-Arg9,[Leu8]-BK, a specific B1 receptor
      antagonist, indicating that the LBK effects were mediated through B2 bradykinin
      receptors. Experiments to desensitize the B2 receptors by repeated stimulation
      have demonstrated that the responses to apical or basolateral LBK were due to
      discrete receptors on the apical or basolateral surface. In epithelia clamped in
      the Ussing chambers, addition of LBK to the apical or basolateral surface evoked
      release of PGE2 into the apical and basolateral bathing solutions over the first
      10 min following hormone addition. LBK added to the basolateral side elicited a
      greater release than it was added to the apical side. Pretreatment of the
      epithelia with piroxicam (5 microM) abolished PGE2 release elicited by apical or
      basolateral LBK and abrogated the Isc induced by basolateral LBK. However, the
      rise in Isc induced by apical LBK was reduced by 31.3% only. The anion secretion
      response to apical LBK was not affected by MDL-12330A, an adenylate cyclase
      inhibitor, but greatly attenuated by thapsigargin, an inhibitor of intracellular
      Ca2+ release. However, the reverse effects were seen for basolateral LBK. It is
      concluded that distinct pathways are involved in the stimulation of anion
      secretion by apical or basolateral LBK. The response to basolateral LBK was COX
      dependent, mediated by PGE2 and involves cAMP as second messenger. In contrast,
      the response to apical LBK is largely COX-independent, not mediated by PCE2 and
      involves Ca2+ as intracellular messenger.

PMID- 12064466
TI  - Malondialdehyde binding to proteins dramatically alters fibroblast functions.
AB  - The regulation of cell metabolism by the surrounding environment is deeply
      altered by the posttranslational nonenzymatic modifications of extracellular
      proteins that occur throughout lifespan in vivo and modify their structural and
      functional properties. Among them are protein adducts formed by components
      generated from oxidative processes, such as malondialdehyde (MDA). We have
      investigated here the effects of MDA-binding to proteins on cultured fibroblast
      functions. Type I collagen and/or serum proteins were incubated with 0-100 mM MDA
      for 3 h before use in fibroblast cultures. In tridimensional lattice cultures,
      MDA-treated collagen inhibited the contracting activity of fibroblasts. A similar
      inhibition of lattice contraction was reproduced by the addition of MDA-treated
      serum to the culture medium. In monolayer cultures, the addition of MDA-modified
      serum proteins completely inhibited fibroblast multiplication without effect on
      initial adhesion steps. MDA-modified proteins decreased the proliferative
      capacities of cells, strongly altered cell cycle progression by blocking passage
      to G2/M phases, and induced apoptotic features in fibroblasts. Our results show,
      for the first time, that MDA-modified proteins are potentially as deleterious as
      free MDA, and could be involved in aging as well as in degenerative complications
      of diseases with increased oxidative stress such as diabetes mellitus or
      atherosclerosis.

PMID- 12064467
TI  - Have p53 gene mutations and protein expression a different biological
      significance in colorectal cancer?
AB  - p53 alterations are considered the most common genetic events in many types of
      neoplasms, including colorectal carcinoma (CRC). These alterations include
      mutations of the gene and/or overexpression of the protein. The aim of our study
      was to assess whether in 160 patients undergoing resective surgery for primary
      operable CRC there was an association between p53 mutations and protein
      overexpression and between these and other biological variables, such as cell DNA
      content (DNA-ploidy) and S-phase fraction (SPF), and the traditional
      clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing
      analysis, were found in 68/160 patients (43%) and positive staining for p53
      protein, detected with the monoclonal antibody DO-7, was present in 48% (77/160)
      of the cases, with agreement of 57% (91/160). In particular, a significant
      association was found between increased p53 expression and genetic alterations
      localized in the conserved regions of the gene or in the L3 DNA-binding domain
      and the specific type of mutation. Furthermore, both overexpression of p53 and
      mutations in the conserved areas of the gene were found more frequently in distal
      than in proximal CRCs, suggesting that they might be "biologically different
      diseases." Although p53 mutations in conserved areas were associated with flow
      cytometric variables, overexpression of p53 and mutations in its L3 domain were
      only related respectively to DNA-aneuploidy and high SPF. These data may reflect
      the complex involvement of p53 in the different pathways regulating cell-cycle
      progression. In conclusion, the combination of the mutational status and
      immunohistochemistry of p53, and flow cytometric data may provide an important
      insight into the biological features of CRCs.

PMID- 12064468
TI  - Oxygen and glucose deprivation induces mitochondrial dysfunction and oxidative
      stress in neurones but not in astrocytes in primary culture.
AB  - In order to investigate the potential neuroprotective role played by glucose
      metabolism during brain oxygen deprivation, the susceptibility of cultured
      neurones and astrocytes to 1 h of oxygen deprivation (hypoxia) or oxygen and
      glucose deprivation (OGD) was examined. OGD, but not hypoxia, promotes
      dihydrorhodamine 123 and glutathione oxidation in neurones but not in astrocytes
      reflecting free radical generation in the former cells. A specific loss of
      mitochondrial complex-I activity, mitochondrial membrane potential collapse, ATP
      depletion and necrosis occurred in the OGD neurones, but not in the OGD
      astrocytes. Furthermore, superoxide anion but not nitric oxide formation was
      responsible for these effects. OGD decreased neuronal but not astrocytic NADPH
      concentrations; this was not observed in hypoxia and was independent of
      superoxide or nitric oxide formation. These results suggest that glucose
      metabolism would supply NADPH, through the pentose-phosphate pathway, aimed at
      preventing oxidative stress, mitochondrial damage and neurotoxicity during oxygen
      deprivation to neural cells.

PMID- 12064469
TI  - Akt pathway mediates a cGMP-dependent survival role of nitric oxide in cerebellar
      granule neurones.
AB  - Apoptotic death results from disrupting the balance between anti-apoptotic and
      pro-apoptotic cellular signals. The inter- and intracellular messenger nitric
      oxide is known to mediate either death or survival of neurones. In the present
      work, cerebellar granule cells were used as a model to assess the survival role
      of nitric oxide and to find novel signal transduction pathways related to this
      role. It is reported that sustained inhibition of nitric oxide production induces
      apoptosis in differentiated cerebellar granule neurones and that compounds that
      slowly release nitric oxide significantly revert this effect. Neuronal death was
      also reverted by a caspase-3-like inhibitor and by a cyclic GMP analogue, thus
      suggesting that nitric oxide-induced activation of guanylate cyclase is essential
      for the survival of these neurones. We also report that the Akt/GSK-3 kinase
      system is a transduction pathway related to the survival action of nitric oxide,
      as apoptosis caused by nitric oxide deprivation is accompanied by down-regulation
      of this, but not of other, kinase systems. Conversely, treatments able to rescue
      neurones from apoptosis also counteracted this down-regulation. Furthermore, in
      transfection experiments, overexpression of the Akt gene significantly decreased
      nitric oxide deprivation-related apoptosis. These results are the first evidence
      for a mechanism where endogenous nitric oxide promotes neuronal survival via
      Akt/GSK-3 pathway.

PMID- 12064470
TI  - Plaque-associated disruption of CSF and plasma amyloid-beta (Abeta) equilibrium
      in a mouse model of Alzheimer's disease.
AB  - To better understand amyloid-beta (Abeta) metabolism in vivo, we assessed the
      concentration of Abeta in the CSF and plasma of APP(V717F) (PDAPP) transgenic
      mice, a model that develops age-dependent Alzheimer's disease (AD)-like
      pathology. In 3-month-old mice, prior to the development of Abeta deposition in
      the brain, there was a highly significant correlation between Abeta levels in CSF
      and plasma. In 9-month-old-mice, an age at which some but not all mice have
      developed Abeta deposition, there was also a significant correlation between CSF
      and plasma Abeta; however, the correlation was not as strong as that present in
      young mice. In further exploring CSF and plasma Abeta levels in 9-month-old mice,
      levels of CSF Abeta were found to correlate highly with Abeta burden. Analysis of
      the CSF: plasma Abeta ratio revealed a selective two-fold increase in plaque
      versus non-plaque bearing mice, strongly suggesting a plaque-mediated
      sequestration of soluble Abeta in brain. Interestingly, in 9-month-old mice, a
      significant correlation between CNS and plasma Abeta was limited to mice lacking
      Abeta deposition. These findings suggest that there is a dynamic equilibrium
      between CNS and plasma Abeta, and that plaques create a new equilibrium because
      soluble CNS Abeta not only enters the plasma but also deposits onto amyloid
      plaques in the CNS.

PMID- 12064471
TI  - Beta-amyloid peptide in regulated secretory vesicles of chromaffin cells:
      evidence for multiple cysteine proteolytic activities in distinct pathways for
      beta-secretase activity in chromaffin vesicles.
AB  - A key factor in Alzheimer's disease (AD) is the beta-secretase activity that is
      required for the production of beta-amyloid (Abeta) peptide from its amyloid
      precursor protein (APP) precursor. In this study, the majority of Abeta secretion
      from neuronal chromaffin cells was found to occur via the regulated secretory
      pathway, compared with the constitutive secretory pathway; therefore, beta
      secretase activity in the regulated secretory pathway was examined for the
      production and secretion of Abeta in chromaffin cells obtained from in vivo
      adrenal medullary tissue. The presence of Abeta(1-40) in APP-containing
      chromaffin vesicles, which represent regulated secretory vesicles, was
      demonstrated by radioimmunoassay (RIA) and reverse-phase high-performance liquid
      chromatography. These vesicles also contain Abeta(1-42), measured by RIA.
      Significantly, regulated secretion of Abeta(1-40) from chromaffin cells
      represented the majority of secreted Abeta (> 95% of total secreted Abeta),
      compared with low levels of constitutively secreted Abeta(1-40). These results
      indicate the importance of Abeta production and secretion in the regulated
      secretory pathway as a major source of extracellular Abeta. Beta-secretase
      activity in isolated chromaffin vesicles was detected with the substrate Z-Val
      Lys-Met-/MCA (methylcoumarinamide) that contains the beta-secretase cleavage
      site. Optimum beta-secretase activity in these vesicles required reducing
      conditions and acidic pH (pH 5-6), consistent with the in vivo intravesicular
      environment. Evidence for cysteine protease activity was shown by E64c inhibition
      of Z-Val-Lys-Met-MCA-cleaving activity, and E64c inhibition of Abeta(1-40)
      production in isolated chromaffin vesicles. Chromatography resolved the beta
      secretase activity into two distinct proteolytic pathways consisting of: (i)
      direct cleavage of the beta-secretase site at Met-/Asp by two cysteine
      proteolytic activities represented by peaks Il-A and Il-B, and (ii) an
      aminopeptidase-dependent pathway represented by peak I cysteine protease activity
      that cleaves between Lys-/Met, followed by Met-aminopeptidase that would generate
      the beta-secretase cleavage site. Treatment of chromaffin cells in primary
      culture with the cysteine protease inhibitor E64d reduced the production of the
      beta-secretase product, a 12-14 kDa C-terminal APP fragment. In addition, BACE 1
      and BACE 2 were detected in chromaffin vesicles; BACE 1 represented a small
      fraction of total beta-secretase activity in these vesicles. These results
      illustrate that multiple cysteine proteases, in combination with BACE 1,
      contribute to beta-secretase activity in the regulated secretory pathway. These
      results complement earlier findings for BACE 1 as beta3-secretase for Abeta
      production in the constitutive secretory pathway that provides basal secretion of
      Abeta into conditioned media. These findings suggest that drug inhibition of
      several proteases may be required for reducing Abeta levels as a potential
      therapeutic approach for AD.

PMID- 12064472
TI  - Distribution, cellular localization and functional role of CCR2 chemokine
      receptors in adult rat brain.
AB  - Recent studies demonstrated that the chemokine monocyte chemoattractant protein-1
      (MCP-1)/CCL2 and its receptor, CCR2, play important roles in various brain
      diseases. In this study, using quantitative autoradiography, we studied the
      pharmacological properties of [125l]MCP-1/CCL2 binding in rat brain and we
      clearly showed the distribution of CCR2 receptors in cerebral cortex, nucleus
      accumbens, striatum, amygdala, thalamus, hypothalamus, hippocampus, substantia
      nigra, mammillary bodies and raphe nuclei. Moreover, using double fluorescent
      immunohistochemistry, we showed that CCR2 receptors were constitutively expressed
      on neurons and astrocytes. Using RT-PCR methods, we demonstrated that CCR2 mRNA
      is present in various brain areas described above. Four hours after an acute
      intraperitoneal lipopolysaccharide injection, we showed that MCP-1/CCL2 binding
      was up-regulated in several brain structures; this effect took place on both
      CCR2B labelled neurons and astrocytes and to a lesser extent on activated
      microglia. To explore neurobiological function of CCR2, actimetric study was
      carried out. After intracerebroventricular injections of MCP-1/CCL2, we showed
      that motor activity was markedly decreased. Our results provide the first
      evidence for constitutive CCR2 receptor expression with precise neuroanatomical
      and cellular localizations in the brain, and its regulation during an
      inflammatory process, suggesting that MCP-1/CCL2 and CCR2 play important
      physiological and pathophysiological role(s) in the CNS.

PMID- 12064473
TI  - Transcriptional activation of nitric oxide synthase-2, and NO-induced cell death,
      in mouse cerebrovascular endothelium exposed to Neisseria meningitidis.
AB  - The site and mechanisms by which meningococci gain access to the CNS are unclear.
      In this study we determined whether production of nitric oxide (NO) is part of
      the host (endothelial cell) response to meningococcal cell lysate, and the
      consequences for endothelial cell viability. Expression of NO synthase type II
      (NOS-2) mRNA, protein and enzyme activity were investigated in mouse
      cerebrovascular endothelial cells exposed to sonicated Neisseria meningitidis.
      The production of nitrite peaked after 48 h of incubation, and this reflected
      transcriptional activation of the NOS-2 gene and increased expression of the NOS
      2 protein. This endothelial response was independent of meningococcal
      lipopolysaccharide production. Endothelial cell death occurred as a result of NO
      production, and addition of a NOS inhibitor prevented cell death, but the cells
      did not exhibit features of apoptosis. However, inhibition of poly (ADP-ribose)
      polymerase (PARP) decreased the rate of cell death by more than 40%. These data
      indicate that N. meningitidis increases expression of NOS-2 in endothelial cells
      and causes cell death. Such an effect could contribute to meningococcal entry
      into the CNS in situ.

PMID- 12064474
TI  - Effect of GP120 on glutathione peroxidase activity in cortical cultures and the
      interaction with steroid hormones.
AB  - GP120 (the protein component of the HIV viral coat) is neurotoxic and may
      contribute to the cell loss associated with AIDS-related dementia. Previously, it
      has been shown in rat cortical mixed cultures that gp120 increased the
      accumulation of hydrogen peroxide and superoxide, two reactive oxygen species
      (ROS). We now demonstrate that gp120 increased activity of the key antioxidant
      glutathione peroxidase (GSPx), presumably as a defensive mechanism against the
      increased ROS load. Both estrogen and glucocorticoids (GCs), the adrenal steroid
      released during stress, blunted this gp120 effect on GSPx activity. The similar
      effects of estrogen and of GCs are superficially surprising, given prior
      demonstrations that GCs exacerbated and estrogens protected against gp120
      neurotoxicity. We find that these similar effects of estrogen and GCs on GSPx
      regulation arose, in fact, from very different routes, which are commensurate
      with these prior reports. Specifically, estrogen has demonstrated antioxidant
      properties that may prevent the ROS increase (therefore acting as a
      neuroprotective agent) and rendered unnecessary the compensatory GSPx increased
      activity. To verify this we have added H2O2 to estrogen + gp120-treated cells,
      and GSPx activity was increased. However, with addition of H2O2 to GCs + gp120
      treated cells there was no increase in activity. GCs appeared to decrease enzyme
      production and or activity and therefore under insult conditions ROS levels rose
      in the cell resulting in increased neurotoxicity. Overexpression of GSPx enzyme
      via herpes vector system reversed the GCs-induced loss of enzyme and eliminated
      the GCs exacerbation of gp120 neurotoxicity.

PMID- 12064475
TI  - Hypotension-induced dopamine release in prefrontal cortex is mediated by local
      glutamatergic projections at the level of nerve terminals.
AB  - In a previous study it was shown that nitroprusside-induced hypotension strongly
      enhances the release of dopamine (DA) in the prefrontal cortex (PFC). In the
      present study we have further investigated the mechanism involved in this effect.
      Glutamate receptor antagonists were infused into the ventral tegmental area (VTA)
      or PFC, while DA release was measured in the ipsilateral PFC and hypotension was
      applied by intravenous infusion of nitroprusside. Infusion into the VTA of
      neither a NMDA receptor antagonist (CPP), nor a non-NMDA antagonist (DNQX)
      affected the hypotension-induced increase of DA in the PFC. Intracortical
      infusion of CPP also failed to affect significantly, whereas local infusion of
      DNQX inhibited the hypotension-enhanced release of DA dose-dependently. The
      stimulation of DA release was relatively small in the VTA as well as in the
      nucleus accumbens when compared with the response in the PFC. It is concluded
      that DA released from mesocortical neurons can be modulated by two different
      mechanisms: first, by glutamate afferents to the VTA that modify the nerve
      impulse flow of DA neurons; and, second, by glutamate afferents to the PFC that
      act at the level of the DA nerve terminals. The behaviour context (arousal or
      stress versus hypotension) determines which type of interaction predominates.

PMID- 12064476
TI  - Dopamine transport function is elevated in cocaine users.
AB  - Dopaminergic transmission has been suggested to be a primary mechanism mediating
      reinforcement, withdrawal and craving associated with psychostimulant addiction.
      Pyscho-stimulants attenuate dopamine transporter (DAT) clearance efficiency,
      resulting in a net increase in synaptic dopamine levels. Re-uptake rate is
      determined by the number of functional DAT molecules at the membrane surface.
      Previous in vivo imaging studies in humans and in vitro studies in post-mortem
      human brain have demonstrated that chronic cocaine abuse results in a
      neuroadaptive increase in DAT-binding site density in the limbic striatum.
      Whether this increase in DAT availability represents an increase in the
      functional activity of the transporter is unknown. Here, we present evidence that
      DAT function is elevated by chronic cocaine abuse. The effect of increasing post
      mortem interval on the functional viability of synaptosomes was modeled in the
      baboon brain. Baboon brains sampled under conditions similar to human brain
      autopsies yielded synaptosomal preparations that were viable up to 24 h post
      mortem. Dopamine (DA) uptake was elevated twofold in the ventral striatum from
      cocaine users as compared to age-matched drug-free control subjects. The levels
      of [3H]DA uptake were not elevated in victims of excited cocaine delirium, who
      experienced paranoia and marked agitation prior to death. In keeping with the
      increase in DAT function, [3H]WIN 35,428 binding was increased in the cocaine
      users, but not in the victims of excited delirium. These results demonstrate that
      DA uptake function assayed in cryopreserved human brain synaptosomes is a
      suitable approach for testing hypotheses of the mechanisms underlying human brain
      disorders and for studying the actions of addictive drugs in man.

PMID- 12064477
TI  - Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and
      inclusion body formation in ventral mesencephalic cultures.
AB  - Mutations in alpha-synuclein, parkin and ubiquitin C-terminal hydrolase L1, and
      defects in 26/20S proteasomes, cause or are associated with the development of
      familial and sporadic Parkinson's disease (PD). This suggests that failure of the
      ubiquitin-proteasome system (UPS) to degrade abnormal proteins may underlie
      nigral degeneration and Lewy body formation that occur in PD. To explore this
      concept, we studied the effects of lactacystin-mediated inhibition of 26/20S
      proteasomal function and ubiquitin aldehyde (UbA)-induced impairment of ubiquitin
      C-terminal hydrolase (UCH) activity in fetal rat ventral mesencephalic cultures.
      We demonstrate that both lactacystin and UbA caused concentration-dependent and
      preferential degeneration of dopaminergic neurons. Inhibition of 26/20S
      proteasomal function was accompanied by the accumulation of alpha-synuclein and
      ubiquitin, and the formation of inclusions that were immunoreactive for these
      proteins, in the cytoplasm of VM neurons. Inhibition of UCH was associated with a
      loss of ubiquitin immunoreactivity in the cytoplasm of VM neurons, but there was
      a marked and localized increase in alpha-synuclein staining which may represent
      the formation of inclusions bodies in VM neurons. These findings provide direct
      evidence that impaired protein clearance can induce dopaminergic cell death and
      the formation of proteinaceous inclusion bodies in VM neurons. This study
      supports the concept that defects in the UPS may underlie nigral pathology in
      familial and sporadic forms of PD.

PMID- 12064478
TI  - Cdk5 phosphorylates p53 and regulates its activity.
AB  - Cyclin dependent kinase 5 (Cdk5) is a proline-direct protein kinase that is most
      active in the CNS, and has been implicated as a contributing factor in certain
      neurodegenerative diseases. Further, there is evidence to suggest that Cdk5 may
      facilitate the progression of apoptosis. However, the mechanisms involved have
      not been elucidated. The tumor suppressor protein p53, a transcription factor
      that is regulated by phosphorylation, increases the expression of genes that
      control growth arrest or cell death. To understand how Cdk5 could facilitate
      apoptosis, the effects of Cdk5 on p53 activity were examined. In the present
      study it is shown that in apoptotic PC12 cells the levels of p53 and Cdk5
      increase concomitantly. Further, Cdk5/p25 effectively phosphorylates recombinant
      p53 in vitro. Transient transfection of Cdk5/p25 into cells results in an
      increase in p53 levels, as well as the expression of the p53-responsive genes p21
      and Bax. Furthermore, evidence is provided that increased Cdk5 activity increases
      p53 transcriptional activity significantly, suggesting that p53 is modulated in
      situ by Cdk5. This is the first demonstration that p53 is a substrate of Cdk5,
      and that Cdk5 can modulate p53 levels and activity.

PMID- 12064479
TI  - Trophic agents that prevent neuronal apoptosis activate calpain and down-regulate
      CaMKIV.
AB  - CaMKIV is enriched in neuronal nuclei and mediates Ca2+-dependent survival via
      transcription factor phosphorylation. Cultured cerebellar granule neurons were
      used to examine whether distinct modes of Ca2+ signaling differentially modulate
      CaMKIV expression and function. For long-term survival, these neurons require 25
      mm KCl or NMDA, which stimulates Ca2+ entry through voltage-sensitive Ca2+
      channels or NMDA receptors (NRs). Lower levels of Ca2+ entry through NRs support
      survival of a neuronal subpopulation grown in 5 mm KCl media. Several effects
      were demonstrated: (i) sustained exposure to 25 mM KCl or 140 microM NMDA
      produced CaMKIV down-regulation, compared to 5 mM KCl cultures; (ii) CaMKIV down
      regulation was attenuated by nifedipine, APV and CaM kinase inhibitors,
      indicating that it is Ca2+ dependent and reversible; (iii) down-regulation was
      both selective for nuclear substrates and calpain-mediated; (iv) proteolysis was
      exacerbated by leptomycin B, a nuclear export inhibitor. Although CaMKIV
      proteolysis by trophic agents seems paradoxical in light of evidence supporting
      its critical role in survival, the CaMKIV/CREB signal transduction pathway was
      preserved, as assessed by CaM kinase-mediated CREB phosphorylation, and the
      ability of CaM kinase inhibitors to interfere with KCl-mediated survival. We
      hypothesize that limited calpain-mediated proteolysis of CaMKIV is a negative
      feedback response to the sustained activation of a Ca2+ and CaMKIV signaling
      pathway by these agents.

PMID- 12064481
TI  - Peptidylarginine deiminase: a candidate factor in demyelinating disease.
AB  - In earlier studies we demonstrated that an increase in the relative amounts of
      citrullinated myelin basic protein (MBP) was found in multiple sclerosis
      (Moscarello et al. 1994). To determine the temporal relationship between the
      citrullinated MBP and peptidylarginine deiminase (PAD), the enzyme responsible
      for deiminating arginyl residues in proteins, we studied enzyme activity, enzyme
      protein, PAD mRNA in a spontaneously demyelinating transgenic mouse model and we
      correlated the amount of PAD with citrullinated MBP. Both PAD protein as measured
      in an immunoslot blot method and PAD RNA were elevated. In fractionation studies
      we showed that the increase in PAD enzyme was due to an increase in the PAD found
      in membrane fractions and not the soluble PAD (PADII). From our data we concluded
      that up-regulation of myelin-associated PAD was responsible for the increase in
      citrullinated MBP in our transgenic mice prior to onset of clinical or
      pathological signs of demyelination. We postulate that a similar mechanism may be
      responsible for the increase in citrullinated MBP in multiple sclerosis.

PMID- 12064480
TI  - Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by
      activation of dopamine D1-type receptors.
AB  - Neurotensin modulates dopaminergic transmission in the nigrostriatal system.
      DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa, is
      phosphorylated on Thr34 by cAMP-dependent protein kinase, resulting in its
      conversion into a potent inhibitor of protein phosphatase-1 (PP 1). Here, we
      examined the effect of neurotensin on DARPP-32 Thr34 phosphorylation using mouse
      neostriatal slices. Neurotensin stimulated DARPP-32 Thr34 phosphorylation by 4-7
      fold with a K(0.5) of approximately 50 nM. The effect of neurotensin was
      antagonized by a combined neurotensin receptor type-1 (NTR1)/type-2 (NTR2)
      antagonist, SR142948. It was not antagonized by a NTR1 antagonist, SR48692 or by
      a NTR2 antagonist, levocabastine; neither was it antagonized by the two combined.
      Pretreatment with TTX or cobalt abolished the effect of neurotensin. The effect
      of neurotensin was antagonized by a dopamine D1 antagonist, SCH23390, and by
      ionotropic glutamate receptor antagonists, MK801 and CNQX. These results indicate
      that neurotensin stimulates the release of dopamine from nigrostriatal
      presynaptic terminals in an NMDA receptor- and AMPA receptor-dependent manner,
      leading to the increase in DARPP-32 Thr34 phosphorylation. Neurotensin stimulated
      the phosphorylation of Ser845 of the AMPA receptor GluR1 subunit in wild-type
      mice but not in DARPP-32 knockout mice. Thus, neurotensin, by stimulating the
      release of dopamine, activates the dopamine D1-receptor/cAMP/PKA/DARPP-32/PP 1
      cascade.

PMID- 12064482
TI  - Functional significance of a highly conserved glutamate residue of the human
      noradrenaline transporter.
AB  - The aim of the study was to investigate the role of glutamate residue 113 in
      transmembrane domain 2 of the human noradrenaline transporter in determining cell
      surface expression and functional activity. This residue is absolutely conserved
      in all members of the Na+- and Cl--dependent transporter family. Mutations to
      alanine (hE113A), aspartate (hE113D) and glutamine (hE113Q) were achieved by site
      directed mutagenesis and the mutants were expressed in transfected COS-7 or HEK
      293 cells. Cell surface expression of hE113A and hE113D, but not hE113Q, was
      markedly reduced compared with wild type, and functional noradrenaline uptake was
      detected only for the hE113Q mutant. The pharmacological properties of the hE113Q
      mutant showed very little change compared with wild type, except for a decrease
      in Vmax values for noradrenaline and dopamine uptake of 2-3-fold. However, the
      hE113D mutant showed very marked changes in its properties, compared with wild
      type, with 82-260-fold decreases in the affinities of the substrates,
      noradrenaline, dopamine and MPP+, and increased Na+ affinity for stimulation of
      nisoxetine binding. The results of the study show that the size and not the
      charge of the 113 glutamate residue of the noradrenaline transporter seems to be
      the most critical factor for maintenance of transporter function and surface
      expression.

PMID- 12064483
TI  - Geldanamycin induces heat shock proteins in brain and protects against focal
      cerebral ischemia.
AB  - Geldanamycin (GA), a benzoquinone ansamycin, binds Hsp90 in vitro, releases heat
      shock factor (HSF1) and induces heat shock proteins (Hsps). Because viral and
      transgenic overexpression of Hsps protects cells against ischemia in vitro, we
      hypothesized that GA would protect brain from focal ischemia by inducing Hsps in
      vivo. Adult male Sprague-Dawley rats were subjected to 2-hour middle cerebral
      artery occlusions (MCAO) using the suture technique followed by 22-h
      reperfusions. GA or vehicle was injected into the lateral cerebral ventricles
      (i.c.v) 24 h before ischemia. Geldanamycin at 1 microg/kg decreased infarct
      volumes by 55.7% (p < 0.01) and TUNEL-positive cells by 30% in cerebral cortex.
      GA also improved behavioral outcomes (p < 0.01) and reduced brain edema (p <
      0.05). Western blots showed that the 1 microg/kg GA dose induced Hsp70 and Hsp25
      protein 8.2-fold and 2.7-fold, respectively, by 48 h following administration.
      Immunocytochemistry showed that GA induced Hsp70 in neurons and Hsp25 in glia and
      arteries in cortex, hippocampus, hypothalamus, and other brain regions. GA
      reduced co-immunoprecipitation of HSF1 with Hsp90 in brain tissue homogenates,
      promoted HSE-binding of HSF in brain nuclear extracts using gel shift assays, and
      increased luciferase reporter gene transcription for the Hsp70 promoter in PC12
      cells. The data show that geldanamycin protects brain from focal ischemia and
      that this may be due, at least in part, to geldanamycin stimulation of heat shock
      gene transcription.

PMID- 12064484
TI  - Neuroprotection by scatter factor/hepatocyte growth factor and FGF-1 in
      cerebellar granule neurons is phosphatidylinositol 3-kinase/akt-dependent and
      MAPK/CREB-independent.
AB  - Neuroprotective actions of scatter factor/hepatocyte growth factor (SF/HGF) have
      not been described. We examined the effects of SF/HGF in comparison to acidic
      fibroblast growth factor-1 (FGF-1) on N-methyl-D-aspartate (NMDA) and quinolinic
      acid (QUIN)-induced excitotoxicity in primary cerebellar granule neurons.
      Exposure to NMDA or QUIN for 24 h resulted in concentration-dependent cell death
      (p < 0.001) that was completely attenuated (p < 0.001) by pre-treatment of cells
      with SF/HGF (50 ng/mL) or FGF-1 (40 ng/mL). SF/ HGF and FGF-1 activated both Akt
      and MAP-kinase > threefold (p < 0.001). Neither SF/HGF nor FGF-1 activated cyclic
      AMP-response element binding protein (CREB), a downstream target of MAP-kinase,
      whereas brain-derived neurotrophic factor (BDNF) activated both MAP-kinase and
      CREB in granule neurons. Neuroprotection against NMDA or QUIN by SF/HGF and FGF-1
      was negated by the addition of LY294002 (10 microM) or wortmannin (100 microM),
      two distinct inhibitors of phosphatidylinositol 3-kinase (P13-K), but not by the
      MAP-kinase kinase (MEK) inhibitor PD98059 (33 microm). Likewise, expression of a
      dominant-negative mutant of Akt (Akt-kd) completely prevented the neuroprotective
      actions of SF/HGF and FGF-1. Overexpression of a constitutively activated Akt
      (Akt-myr) or wild-type Akt (wtAkt) attenuated excitotoxic cell death. These data
      show that both SF/HGF and FGF-1 protect cerebellar granule neurons against
      excitotoxicity with similar potency in a P13-K/Akt-dependent and MAP-kinase/CREB
      independent manner.

PMID- 12064486
TI  - AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during
      development of oligodendrocytes.
AB  - Cells of the oligodendroglial lineage express Ca2+-permeable alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate-preferring glutamate receptors (AMPA-GluR)
      during development. Prolonged activation of their AMPA-GluR causes Ca2+ overload,
      resulting in excitotoxic death. Prior studies have shown that oligodendroglial
      progenitors and immature oligodendrocytes are susceptible to excitotoxicity,
      whereas mature oligodendrocytes are resistant. An unresolved issue has been why
      Ca2+-permeability of AMPA-GluR varies so markedly with oligodendroglial
      development, although the level of expression of edited GluR2, an AMPA-GluR
      subunit which blocks Ca2+ entry, is relatively constant. To address this
      question, we performed Ca2+ imaging, molecular and electrophysiological analyses
      using purified cultures of the rat oligodendroglial lineage. We demonstrate that
      transient up-regulation of expression of GluR3 and GluR4 subunits in
      oligodendroglial progenitors and immature oligodendrocytes results in the
      assembly by these cells, but not by oligodendroglial pre-progenitors or mature
      oligodendrocytes, of a population of AMPA-GluR which lack GluR2. This stage
      specific up-regulation of edited GluR2-free, and hence Ca2+-permeable, AMPA-GluR
      explains the selective susceptibility to excitotoxicity of cells at these stages
      of oligodendroglial differentiation, and is likely to be important to these cells
      in the trans-synaptic Ca2+-signaling from glutamatergic neurons, which occurs in
      hippocampus

PMID- 12064485
TI  - Instrumental role of Na+ in NMDA excitotoxicity in glucose-deprived and
      depolarized cerebellar granule cells.
AB  - In glucose-deprived cerebellar granule cells, substitution of extracellular Na+
      with Li+ or Cs+ prevented N-methyl-D-aspartate (NMDA)-induced excitotoxicity.
      NMDA stimulated 45Ca2+ accumulation and ATP depletion in a Na-dependent manner,
      and caused neuronal death, even if applied while Na,K-ATPase was inhibited by 1
      mM ouabain. The cells treated with NMDA in the presence of ouabain accumulated
      sizable 45Ca2+ load but most of them failed to elevate cytosolic [Ca2+] upon
      mitochondrial depolarization. Na/Ca exchange inhibitor, KB-R7943, inhibited Na
      dependent and NMDA-induced 45Ca2+ accumulation but only if Na,K-ATPase activity
      was compromised by ouabain. In cells energized by glucose and exposed to NMDA
      without ouabain, KB-R7943 reduced NMDA-elicited ionic currents by 19% but failed
      to inhibit 45Ca2+ accumulation. It appears that a large part of NMDA-induced Ca2+
      influx in depolarized and glucose-deprived cells is mediated by reverse Na/Ca
      exchange. A high level of reverse Na/Ca exchange operation is maintained by a
      sustained Na+ influx via NMDA channels and depolarization of the plasma membrane.
      In cells energized by glucose, however, most Ca2+ enters directly via NMDA
      channels because Na,K-ATPase regenerating Na+ and K+ concentration gradients
      prevents Na/Ca exchange reversal. Since under these conditions Na/Ca exchange
      extrudes Ca2+, its inhibition destabilizes Ca2+ homeostasis.

PMID- 12064487
TI  - 5-Iodo-A-85380 binds to alpha-conotoxin MII-sensitive nicotinic acetylcholine
      receptors (nAChRs) as well as alpha4beta2* subtypes.
AB  - Recent work suggests that 5-iodo-A-85380, a radioiodinated analog of the 3
      pyridyl ether A-85380, represents a promising imaging agent for non-invasive, in
      vivo studies of alphaAbeta2* nicotinic acetylcholine receptors (nAChRs; *denotes
      receptors containing the indicated subunits), because of its low non-specific
      binding, low in vivo toxicity and high selectivity for alpha4beta2* nAChRs. As an
      approach to elucidate nAChR subtypes expressed in striatum, we carried out
      competitive autoradiography in monkey and rat brain using 5-[125I]iodo-A-85380
      ([125I]A-85380) and [125I]alpha-conotoxin MII, a ligand that binds with high
      affinity to alpha6* and alpha3* nAChRs, but not to alpha4beta2* nAChRs. Although
      A-85380 is reported to be selective for alpha4beta2* nAChRs, we observed that A
      85380 completely inhibited [125I]alpha-conotoxin MII binding in rat striatum and
      that A-85380 blocked >90% of [125I] alpha-conotoxin MII sites in monkey caudate
      and putamen. These results suggest that A-85380 binds to non-alpha4beta2* nAChRs,
      including putative alpha6* nAChRs. Experiments to determine the percentage of
      [125I]A-85380 sites that contain alpha-conotoxin MII-sensitive (alpha6beta2*)
      nAChRs indicate that they represent about 10% of [125I]A-85380 sites in rodent
      striatum and about 30% of sites in monkey caudate and putamen. These data are
      important for identifying alterations in nicotinic receptor subtypes in
      Parkinson's disease and other basal ganglia disorders both in in vitro and in in
      vivo imaging studies.

PMID- 12064488
TI  - Cost effectiveness and risk assessment.

PMID- 12064489
TI  - Does prevention pay?

PMID- 12064490
TI  - Evaluation of pumice, fissure enameloplasty and air abrasion on sealant
      microleakage.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate microleakage of pit
      and fissure sealants after using three different pit and fissure preparation
      techniques: (1) traditional pumice prophylaxis and acid etching, (2) fissure
      enameloplasty and acid etching and (3) air abrasion and acid etching. METHODS:
      Sixty extracted third molars with no clinical evidence of caries were randomly
      divided into 3 groups of 20 each. Teeth were prepared using 1 of 3 occlusal
      surface treatments prior to placement of Delton opaque light-cured sealant. The
      teeth were thermocycled between 5 +/- 2 degrees C and 55 +/- 2 degrees C for 500
      cycles with a dwell time of 30 seconds and then stored in 0.9% normal saline. All
      teeth were sealed apically and coated within 1.5 mm of the sealant margin with
      two layers of nail varnish. The teeth were immersed in a 1% solution of methylene
      blue for 24 hours to allow dye penetration into possible gaps between enamel and
      sealant. Three buccolingual cuts parallel to the long axis of the tooth were made
      yielding 4 sections and 6 surfaces per tooth for analysis. The surfaces were
      scored 0 to 3 for extent of microleakage using a binocular microscope at 25X
      magnification. RESULTS: Kruskal-Wallis and t tests revealed no significant
      difference in microleakage between the 3 fissure preparation methods prior to
      sealant placement. CONCLUSIONS: Neither air abrasion nor enameloplasty followed
      by acid etching produced significantly less microleakage than the traditional
      pumice prophylaxis with acid etching technique.

PMID- 12064491
TI  - Topical antimicrobial therapy in the prevention of early childhood caries: a
      follow-up report.
AB  - PURPOSE: The purpose of this study was to assess the efficacy of antimicrobial
      therapy in the prevention of early childhood caries (ECC). METHODS: The study
      population consisted of 83 subjects (age: 12 to 19 months (x= 15.6); gender: 40
      females and 43 males). Inclusion criteria included: (1) unremarkable medical
      history; (2) presence of 4 maxillary primary incisors (MPI) with no visible
      defects; (3) clinically caries free; (4) use of a nursing bottle at naptime
      and/or bedtime which contained a cariogenic substrate; (5) 2 consecutive ms
      positive cultures from pooled MPI plaque. The subjects were randomized into 2
      groups. The 39 subjects in the experimental group and the 44 subjects in the
      control group were evaluated every 2 months during the study period. At each
      evaluation, the subjects had 10% povidone iodine (experimental group) or placebo
      (control group) applied to their dentition. Treatment failure was defined as the
      appearance of a white spot lesion(s) on any of the MPI during the study period.
      RESULTS: Using the Kaplan-Meier procedure, the estimated percents (+/- SES) of
      participants to experience 12 months of disease-free survival were 91 +/- 5% for
      those receiving treatment and 54 +/- 9% for those in the control group. Via the
      log-rank test, the hazard of treatment failure is statistically significantly
      higher in the placebo group (log-rank statistic 10.28, two-sided P=0.0013).
      CONCLUSIONS: These observations indicate that topical antimicrobial therapy
      increases disease-free survival in children at high risk for ECC.

PMID- 12064492
TI  - The effects of oral conscious sedation on future behavior and anxiety in
      pediatric dental patients.
AB  - PURPOSE: This study investigated the relationship between oral conscious sedation
      and subsequent behavior in the dental setting. METHODS: The sample consisted of
      38 children between the ages of 39 to 71 months (mean=50 months) who had been
      treated with oral sedation 2 to 34 months(mean=13 months) previously, and a
      control group of 38 children, matched by age (mean=51 months) and gender, who had
      received dental treatment without conscious sedation or general anesthesia one
      week to 3 years previously. Subjects were matched by age and gender. All children
      received a standard recall examination and a prophylaxis, during which behavior
      and anxiety were measured. Independent variables included age at the time of
      sedation, present age, gender, time elapsed since sedation, effectiveness of
      sedation, parental scores on Corah's Dental Anxiety Scale and parent's answers to
      a questionnaire. The dependent variables were child behavior (rated with the 4
      point Frankl scale) and self-reported anxiety ratings. RESULTS: Both groups had
      mean behavior ratings of positive or very positive (experimental group mean=3.13;
      control group mean=3.34). There were no statistically significant differences
      between the groups and there was little correlation of independent and dependent
      variables. CONCLUSIONS: There is no relationship between oral conscious sedation
      and the future behavior of children in the dental setting.

PMID- 12064493
TI  - Success rate of formocresol pulpotomy in primary molars restored with stainless
      steel crown vs amalga.
AB  - PURPOSE: The purpose of this retrospective study was to compare the success rates
      of formocresol pulpotomy in primary molars restored with stainless steel crowns
      (SSC) to those restored with amalgam (AM). METHODS: Radiographs of pulpotomized
      primary molars restored with SSC or AM in the principal author's pediatric
      dentist practice were evaluated and defined as a "failure" when one or more of
      the following signs were present: internal (IR) or external (ER) root resorption
      and periapical (PR) or inter-radicular (IRR) radiolucency. Pulp canal
      obliteration was not regarded as failure. Three hundred and forty-one molars were
      available for follow-up evaluations ranging from 6 to 103 months. RESULTS: Forty
      seven (14%) teeth were defined as "failure," with a rate of 13% (36/287) for
      teeth restored with SSC and 20% (11/54) for AM. This difference was not
      statistically significant (P>0.1). Failure rates of 2 surfaces AM was 23% (7/30),
      much higher than that of one surface AM (10%, 2/20). Most of the failed teeth
      presented more than one pathologic finding, with IR being the most frequently
      observed (36%), followed by ER (31%), IRR (22%) and PR (11%). Pulp canal
      obliteration was detected in 80% of the teeth, with similar rates in both groups.
      Failures were observed initially after a mean follow-up of 27 and 29 months in
      teeth restored with AM and SSC, respectively. CONCLUSIONS: Pulpotomized primary
      molars can be successfully restored with one surface amalgam if their natural
      exfoliation is expected within not more than two years.

PMID- 12064494
TI  - The success of emergency pulpotomies in primary molars.
AB  - PURPOSE: The purpose of this retrospective study was to assess the success of
      pulpotomies performed on an emergency basis and restored with a temporary zinc
      oxide eugenol restorative material. METHODS: Records were collected from 216
      pulpotomies in primary molars performed on an emergency basis by pediatric dental
      residents at the University of Florida pediatric dental clinic between July 1999
      and June 2001. The selection criteria include teeth with a positive history of
      pain but with absence of clinical and radiographic signs of pulp degeneration.
      Formocresol was the medicament used and the teeth were restored temporarily with
      a reinforced zinc-oxide eugenol material. Treatment success or failure was
      determined, at the definitive restorative appointment, by the presence or absence
      of clinical and/or radiographic pathology. The time interval between emergency
      and definitive treatment appointments, tooth-type, arch, age, and gender were the
      variables analyzed in this study. Chi-square analysis was used to assess the
      effect of the different variables on the outcome of the treatment. RESULTS: Sixty
      four teeth were available for assessment in the two-year period. A 53% success
      rate was observed, if the tooth was evaluated and restored with the definitive
      restoration, within the first 90 days post-emergency treatment. A 31% success
      rate was observed after 365 days. These results were statistically significant
      (P=0.016). Patients younger than six years old showed statistically significant
      higher chances for success than older children did (P=0.018). No significant
      differences were found for gender, type of tooth, or arch. CONCLUSIONS: The low
      success rate found during the first three months post emergency treatment may be
      attributed to undiagnosed, subclinical inflamed pulp, while long-term failure may
      be associated with microleakage of the temporary restorative material.

PMID- 12064496
TI  - Patients with special health care needs in pediatric dental practices.
AB  - PURPOSE: The objective of this study was to determine the involvement of
      pediatric dentists in practice in managing patients with special health care
      needs (SCHN) upon completion of training. METHODS: A questionnaire was developed,
      pilot tested, modified and sent to a randomly selected sample of 950 pediatric
      dentists in practice who were active and fellow members of the American Academy
      of Pediatric Dentistry. RESULTS: Fifty-one percent of the dentists responded. The
      majority were males between the ages of 41 and 50 years. Most practiced in
      communities with over 500,000 citizens. Most were trained in hospital-based
      programs, and 84% reported comprehensive didactic courses on SHCN patients during
      training. SCHN patients were routinely appointed in an integrated schedule in
      their practices. Seventy-one percent of responders continue to follow the
      patients after 21 years of age. Most had buildings and offices that were
      handicapped accessible. Patient profiles remained similar since initiating
      private practice with notable increases reported in the new and recall patients
      and patients with complicated medical histories categories. CONCLUSIONS: The
      results of this survey demonstrate the continuing involvement of pediatric
      dentists in private practice in scheduling and treating patients with special
      health care needs after the completion of training.

PMID- 12064495
TI  - Association between bispectral analysis and level of conscious sedation of
      pediatric dental patients.
AB  - PURPOSE: This preliminary investigation evaluated the associations among multiple
      factors designed to measure depth of sedation, such as changes in the patient's
      electroencephalogram (EEG) via a bispectral analysis (BIS), other physiological
      variables, observed behaviors and clinical assessment of sedation levels
      consistent with the American Academy of Pediatric Dentistry (AAPD) sedation
      guidelines. METHODS: Thirty-four healthy pediatric patients between three to six
      years of age were enrolled in this institutionally approved study. All children
      required dental restorations and were uncooperative. The children received a
      routine oral sedation regimen used in our clinic consisting of chloral hydrate,
      meperidine, and hydroxyzine that varied in dose for each child. Intraoperatively,
      nitrous oxide/oxygen was also administered. Physiological variables including
      oxygen saturation, blood pressure and heart rate were recorded in compliance with
      AAPD sedation guidelines. The behavior and levels of sedation consistent with
      AAPD guidelines were also recorded. The BIS monitor was used to obtain EEG
      information. RESULTS: Useful data were recorded from 21 patients. The mean age
      and weight of the children were 46.1 +/- 10 months and 16.1 +/- 5 kgs,
      respectively. The results show a significant association between observed patient
      behavior and the AAPD levels of sedation (chi2 = 105.1, df = 6, P< 0.0001),
      between levels of sedation and behavior as a function of 12 time-oriented periods
      during treatment, (chi2=41.90, df=22, P<0.005 and chi2=48.0, df=33, P=0.04,
      respectively) and between BIS readings as a function of both level of sedation
      and behavior (chi2=105.1, df=6, P<0.001 and chi2=28.5, df = 18, P< 0.05,
      respectively). CONCLUSIONS: There appears to be a significant association between
      observed patient behaviors during sedation and levels of sedation as measured by
      BIS and AAPD sedation guidelines. The study also showed that, under treatment
      conditions used in this study, BIS does not appear to be a more valid means of
      monitoring sedation depth than the current commonly accepted methods.

PMID- 12064497
TI  - Dental caries among disadvantaged 3- to 4-year-old children in northern
      Manhattan.
AB  - PURPOSE: The study was conducted to determine the prevalence of early childhood
      caries (ECC), untreated caries, and the ratio of posterior to anterior caries in
      a disadvantaged predominantly Hispanic or African-American urban population. Data
      are compared to NHANES III to assess the caries burden in our cohort. Comparisons
      are made to the aggregate and to minorities within the national database.
      METHODS: A retrospective chart review was conducted for children enrolled in a
      Head Start or day care program in the communities of Washington-Heights and
      Central and East Harlem and seen on the community organization's mobile dental
      van between 1995 and 1997. The study included only children 3 to 4 years of age
      at the initial examination (n=1,605). A single examiner provided all the
      examinations. The mean number of decayed and filled surfaces (dfs), decayed
      surfaces (ds) and filled surfaces (fs), the percentage of decayed of total
      decayed and filled surfaces (%d/dfs), decayed and filled teeth (dft), decayed
      teeth (dt) and filled teeth (ft), and the percentage of decayed of total decayed
      and filled teeth (%d/dft) were calculated. Posterior vs anterior d, f, dft, dfs
      and d-anterior/total d, and d-posterior/total d were tabulated. Northern
      Manhattan data was tabulated and compared to NHANES III (1988-1994) in the
      aggregate and for subpopulations categorized by gender and ethnicity. All results
      are also reported for children with at least one decayed or filled tooth. T-tests
      were used to assess for significant differences. RESULTS: There was even
      representation of males (50%) and females (50%). Mean dft was 1.08 overall, and
      3.14 for children with dft>0. The level of untreated decay, %d/ dft, was 91%,
      significantly higher than the US national population which is 76% overall, and
      76% for African Americans and Mexican Americans within the US national
      population. CONCLUSIONS: The children in this population have higher caries
      prevalence and a higher level of untreated caries than the national means as
      reported in NHANES III. The high level of untreated decay found in this
      particularly disadvantaged community suggests that enhanced dental services
      targeting the very young are needed in these communities.

PMID- 12064500
TI  - The etch-bleach-seal technique for managing stained enamel defects in young
      permanent incisors.
AB  - Hypomineralized enamel defects frequently are manifest as a mottled-white
      appearance and can be associated with variable degrees of discrete yellow-brown
      intrinsic staining. Numerous treatment approaches have been proposed, ranging
      from bleaching to enamel reduction to restorative techniques. Bleaching of
      hypomineralized enamel lesions, using 1 to 2 applications (10 to 15 minutes each)
      of 5% sodium hypochlorite, has been applied clinically. Treatment using this
      approach has proven successful in removing yellow-brown discolorations from
      lesions in young permanent teeth. Young permanent incisors with yellow-brown
      intrinsic discolorations can often be treated by a simple and conservative
      bleaching protocol using sodium hypochlorite.

PMID- 12064498
TI  - The impact of dental benefits on the utilization of dental services by low-income
      children in western Pennsylvania.
AB  - PURPOSE: This study examines the impact of dental coverage provided through a
      health insurance program for low-income children on the use of dental services in
      Western Pennsylvania. METHODS: A before-after design with a control group was
      used. Telephone interviews were conducted with the families of newly enrolled
      children at the time of enrollment, at 6 months and at 12 months after
      enrollment. Both structured and open-ended questions were asked about the use of
      health care services, unmet need/delayed care and causes and consequences of
      unmet need/delayed care. A second group of families were interviewed 12 months
      after the study group was initially interviewed to form a comparison sample. The
      study population consisted of 750 children who were continuously enrolled in the
      program for 12 months and 460 comparison children. RESULTS: After enrollment, the
      proportion of children with a regular source of dental care increased 42%, while
      the proportion of those who had a preventive dental visit increased 50%. The
      proportion of children reporting unmet need/delayed care for dental services fell
      from 43% to 10%. The program had a larger impact on the use of dental services
      than on the use of medical services. CONCLUSIONS: The extension of dental
      benefits to SCHIP-eligible children in Western Pennsylvania had a positive impact
      on children by increasing their access to dental care and to preventive dental
      services.

PMID- 12064499
TI  - Indirect pulp treatment: in vivo outcomes of an adhesive resin system vs calcium
      hydroxide for protection of the dentin-pulp complex.
AB  - PURPOSE: The purpose of this prospective and randomized in vivo study was to
      compare the clinical and radiographic outcomes of an adhesive resin system vs a
      calcium hydroxide liner for protection of the dentin-pulp complex of primary
      molars treated with indirect pulp treatment. METHODS: Forty-eight primary molars
      with deep occlusal caries, but without preoperative signs and symptoms of
      irreversible pulpitis, received indirect pulp treatment and were restored with a
      composite resin (Z100). The teeth were randomly divided into 2 groups according
      to the material used for protection of the dentin-pulp complex: (1) adhesive
      resin system (Scotchbond MultiPurpose); and (2) calcium hydroxide liner (Dycal).
      These teeth were evaluated clinically and radiographicaly for 2 years. RESULTS:
      After 2 years, 83% (19/23) of the teeth treated with calcium hydroxide and 96%
      (24/25) of teeth treated with only the adhesive resin system presented a
      successful outcome, as determined by clinical and radiographic examination.
      Interradicular and/or periapical lesions were the most predominant signs of
      treatment failure, since 3 out of 23 teeth treated with calcium hydroxide and 1
      out of 25 teeth treated with only adhesive resin presented this outcome. One
      tooth treated with the calcium hydroxide liner was diagnosed with internal root
      resorption at the 18-month examination. Of the 5 teeth diagnosed from radiographs
      as a failure of the indirect pulp treatment, none presented clinical
      signs/symptoms of pulpitis or necrosis such as the presence of fistula, enhanced
      tooth mobility, or pain. CONCLUSIONS: This study demonstrates that protection of
      the dentin-pulp complex of primary molars with an adhesive resin system results
      in similar clinical and radiographic 2-year outcomes as compared to calcium
      hydroxide when indirect pulp treatment is performed in Class I composite
      restorations.

PMID- 12064501
TI  - Hereditary gingival fibromatosis with distinct dental, skeletal and developmental
      abnormalities.
AB  - A case of a 9-year-old child with hereditary gingival fibromatosis, supernumerary
      tooth, chest deformities, auricular cartilage deformation, joint laxity and
      undescended testes is described. The exact mode of inheritance is unclear; a new
      mutation pattern is possible. These features resemble but differ from the
      previously reported Laband syndrome. The dental treatment consisted of surgical
      removal of the fibrous tissue and conservative restorative treatment under
      general anesthesia. The dental practitioner should be alert for developmental
      abnormalities such as supernumerary teeth and delayed tooth eruption. A
      comprehensive medical history and physical systemic evaluation is essential to
      rule out other systemic abnormalities. Genetic consultation is mandatory for
      future family planing.

PMID- 12064502
TI  - Oral health status of preschool children attending Head Start in Maryland, 2000.
AB  - PURPOSE: The objective of this study was to determine the oral health status of
      preschool children attending Head Start Centers in Maryland. METHODS: Clinical
      caries examinations were conducted on 482 children between ages 3-5 from 37
      Maryland Head Start Centers in 2000. Additionally, 560 questionnaires were
      completed by their caretakers regarding their child's access to care, potential
      caries risk factors and history of toothaches. RESULTS: The overall prevalence of
      untreated decay was 52%, with a higher prevalence found in rural than urban
      centers (64% vs 48%). For all children, the mean decayed, filled surfaces (dfs)
      was 3.64, while the mean decayed surfaces (ds) was 2.90. For those who had caries
      experience, the dfs was 6.67 and the ds was 5.32. The percentage of children with
      caries increased by age from 43% for three-year-olds to 62% for four-year-olds.
      Of those children with caries experience, 17% had complained of a toothache and
      9% reportedly cried because of a toothache. CONCLUSIONS: Of significance in this
      study were the findings that: caries is highly prevalent in this underserved
      preschool population; pain due to dental caries is not uncommon; and there is
      little utilization of dental care despite federally mandated and Head Start and
      Medicaid requirements.

PMID- 12064503
TI  - Prediction of mandibular growth in Japanese children age 4 to 9 years.
AB  - PURPOSE: The purpose of this study was to propose mathematical models for
      predicting mandibular growth direction and amount in children with normal
      skeletal relationship from 4 to 9 years of age using the craniofacial
      characteristics found on the head films. METHODS: Lateral cephalograms of 27
      Japanese children with normal occlusion at 4 (T1) and 9 (T2) years of age were
      traced and measured. Fifteen linear and angular measurements were performed. The
      angle NSGn and the distance S-Gn were used to represent the growth direction of
      the mandible and its growth amount, respectively. The data were analyzed by
      multiple linear regression analysis. RESULTS: The multiple regression analysis
      revealed 2 models for the mandibular growth prediction. The equation (model) for
      the mandibular growth direction is YD=-39.844+1.206 X1 +0.333 X2, where YD is the
      predicted value of the angle NSGn at T2. X1 is the value of the angle NSGn at T1
      and X2 is the value of the angle SNB at T1 (R2=0.719, P<0.05). The equation for
      the mandibular growth amount is YA=99.052+0.782 X3-0.517 X4, where YA is the
      predicted value of the distance S-Gn at T2. X3 is the distance S-Gn at T1 andX4is
      the angle NSAr at T1 (R2=0.610, P< 0.05). CONCLUSIONS: The direction of the
      mandibular growth at 9 years of age can be predicted by 72% with the regression
      equation using the angles NSGn and SNB at 4 years of age. The amount of growth of
      the mandible can be predicted by 62% by using the distance S-Gn and the angle
      NSAr at 4 years old. The model for the growth amount provides a relatively lower
      predictive value than that of the growth direction.

PMID- 12064504
TI  - Inner ear pressure changes following square wave intracranial or ear canal
      pressure manipulation in the same guinea pig.
AB  - Inner ear pressure was measured in scala tympani with a micropipette during
      square wave pressure manipulation of the intracranial compartment and,
      subsequently, of the external ear canal (EEC) in the same guinea pig. As
      expected, the combination of the cochlear aqueduct and the inner ear behaves as a
      low-pass filtering system for intracranial pressure manipulation and as a
      complementary high-pass system for ear canal pressure manipulation. Time
      constants for pressure equalization were in the order of seconds and depended on
      the direction of flow through the cochlear aqueduct. Pressure equalization curves
      could not be fitted to a single exponential function; more complicated functions
      were needed for good fits, showing that the pressure equalization process is
      nonlinear. This means that the flow resistance of the cochlear aqueduct and/or
      the compliance of the cochlear windows is not constant, which is in accordance
      with a flow-direction dependent resistance of the cochlear aqueduct. An
      explanation for this can be found in the special structure of the periotic duct
      inside the aqueduct.

PMID- 12064505
TI  - Genetic predisposition for tympanosclerotic degeneration.
AB  - Atherosclerosis and tympanosclerosis are disorders that affect different organs
      in the body. When tissue samples taken from atherosclerotic and tympanosclerotic
      lesions are compared under light and electron microscopes, common pathological
      characteristics become apparent in both tissues. These similarities indicate that
      genetic predisposition to atherosclerosis is also seen in the middle ear. For the
      purpose of evaluating this genetic predisposition, the incidence of
      tympanosclerosis in atherosclerotic patients was examined and compared with the
      normal population. Otoscopic examination of 1,024 atherosclerotic patients was
      performed, and myringosclerosis was revealed in 66.6%. Myringosclerosis was found
      in 36 out of 300 non-atherosclerotic patients (12%). In the group of
      atherosclerotic patients, 174 individuals had past histories of previous ear
      infections. Myringosclerosis was detected in 147 of these patients (84.5%) during
      ear examinations. In 637 non-atherosclerotic patients with histories of ear
      infections, this figure was 114 (17.7%). The high rate of tympanosclerosis
      observed in atherosclerotic patients in comparison to the normal population was
      found to be statistically significant. These findings indicate that there must be
      a genetic predisposition for sclerotic degeneration in some individuals.

PMID- 12064506
TI  - The methodical collection of ear surgery data as a basis for quality control.
AB  - Data relating to daily clinical practice were collected in an otologic database.
      Over a period of 3 years, information was gathered about 1,000 ear operations.
      This led to the following conclusions: the collection of data is difficult; the
      selection of data and the moment it should be fed into the systems are very
      important; there is a risk of using too many items and therefore reducing surgeon
      compliance. On the other hand, too few items result in irrelevant overviews. The
      collection of ear surgery data makes it easier to understand positive and
      negative outcomes.

PMID- 12064507
TI  - Hypothyroidism in patients treated with total laryngectomy. A multivariate study.
AB  - One of the complications of the treatment of head and neck carcinoma patients is
      hypothyroidism. The objective of our study was to quantify the prevalence of
      hypothyroidism in patients with laryngeal or hypopharyngeal cancer treated with a
      total laryngectomy and to evaluate the importance of different variables in the
      appearance of hypothyroidism in this group of patients. A transversal study in
      182 patients treated with total laryngectomy between 1986 and 1998 was carried
      out. TSH and FT4 were determined in all patients. Hypothyroidism was classified
      as subclinical (increased TSH and normal T4 levels) and clinical (increased TSH
      and decreased T4 levels). Univariate and multivariate analysis was carried out to
      examine the relationship between hypothyroidism and different variables. Our
      results showed that the prevalence of hypothyroidism in our group of patients was
      52% (27% subclinical and 25% clinical). Sex, initial extension of the tumour,
      hemithyroidectomy, use of chemotherapy and radiotherapy were variables associated
      with the appearance of hypothyroidism in the univariate analysis (P < 0.05). When
      all these variables were included in a multivariate study, only hemithyroidectomy
      (RR 3,6; CI 95% 1,7-7,2) and combined treatment with radiotherapy (RR 3,4; CI 95%
      1,2-9,6) appeared as prognostic factors. In conclusion, hypothyroidism is a
      frequent complication in patients treated with a total laryngectomy (52%),
      especially when this treatment includes hemithyroidectomy and/or radiotherapy. We
      consider that it is important to check the thyroid function periodically in these
      patients to obtain early diagnosis and appropriate treatment.

PMID- 12064508
TI  - Relation between mood, social support and the quality of life in patients with
      laryngectomies.
AB  - Two hundred laryngectomized members of the Norwegian Society of Laryngectomies
      (NSL), a subsidiary of the Norwegian Cancer Society, were invited to answer the
      EORTC QLQ-C30 (version 3.0) and QLQ-H&N35 QOL questionnaires to assess their
      quality of life (QOL). The Beck Depression Inventory (BDI) scores, their levels
      of social support and their marital and educational statuses were also
      determined. In addition, the activity levels of each patient within the NSL were
      assessed. The questionnaires were returned anonymously by 104 patients. The
      results of this sample were compared with the responses to the EORTC QLQ
      C30/H&N35 by all of the survivors of treatment for head and neck squamous cell
      carcinoma (HNSCC) in western Norway between 1992 and 1997. This sample included
      96 of 106 eligible patients. The QLQ-C30 symptom scores include, e.g., dyspnea,
      smell and taste. However, neither the QLQ-C30 functional scores nor the disease
      specific scores of the people with laryngectomies differed from the general HNSCC
      treated population. The level of social support by family, friends and neighbors
      was not associated with the QOL, whereas high BDI scores were associated with
      reduced QOL by most measured indexes. Furthermore, a positive association was
      determined between the level of activity within the NSL and QOL. This relation
      was to some extent secondary to differential BDI scores. In conclusion, the QOL
      of people with laryngectomies is relatively similar to a general population of
      patients treated because of HNSCC, is related to the activity level within a
      patient interest organization and is associated with a lower mood level.

PMID- 12064509
TI  - Analysis of sex-hormone-receptor expression in laryngeal carcinoma.
AB  - There are significant differences in how laryngeal cancer affects the two
      genders, with cases occuring predominantly in males. This has been speculated to
      result from the different susceptibilities of the tumor cells to steroid sex
      hormones. Since the sex hormone action is mediated by specific cellular
      receptors, several previous studies have analyzed the presence of these sex
      hormone receptors. However, the data on the receptor status for androgen,
      estrogen and progesterone receptors in laryngeal carcinomas are controversial.
      Since some authors have suggested antiandrogen or antiestrogen therapy as an
      adjuvant treatment for laryngeal carcinoma, we performed a comprehensive study
      using immunomorphological and biochemical techniques on both in-vivo and in-vitro
      tumor cells in order to clarify whether major sex-hormone receptors are present
      or not. We performed an immunohistochemical analysis on 13 patients with
      laryngeal carcinomas, 8 males and 5 females, using monoclonal antibodies against
      androgen, estrogen and progesterone receptors. In addition, the presence of
      estrogen and progesterone receptors was tested biochemically using an enzyme
      immune assay (EIA). Furthermore, we analyzed immunohistochemically the expression
      of the hormone receptors in five keratinocyte cell lines originating from
      laryngeal carcinomas. In all of our tumor samples, as well as in the five tumor
      cell lines tested, we did not detect any specific immunohistochemical staining
      for androgen, estrogen and progesterone receptors in the laryngeal carcinoma
      cells when compared to the positive controls of breast and prostate cancer
      samples. Similarly, the biochemical analysis did not demonstrate any significant
      amount of receptor protein in the analyzed cases. In conclusion, the absence of
      male and female sex-hormone receptors strongly argues against laryngeal
      carcinomas being sex-hormone-dependent tumors. Therefore, we do not see any
      rational indication to use a specific antiandrogen or antiestrogen therapy for
      the adjuvant treatment of laryngeal carcinomas.

PMID- 12064510
TI  - Laryngeal chondrosarcoma: a report of five cases.
AB  - Laryngeal chondrosarcoma is a rare tumor that is known for its indolent course
      and its tendency to ultimate recurrence. According to the actually adopted
      classification, 95% of the reported cases are of a low-grade type. A consensus
      recognizing conservative surgery as the most reasonable treatment for these
      lesions has almost been reached. However, fear of jeopardizing the patency of the
      laryngeal airway as a result of a wide cricoid excision and also the fear of
      repeated recurrences could still push some surgeons to perform a total
      laryngectomy in the case of laryngeal chondrosarcoma. After a brief review of the
      literature, we will present five cases of laryngeal chondrosarcoma that were
      treated and followed at the Clermont-Ferrand University Medical Center over the
      last two decades. These cases exhibit many of the clinicopathologic features of
      the tumor and illustrate the pitfalls of diagnosis and treatment. In light of
      this presentation, we will discuss the widely accepted management as well as a
      newly suggested treatment modality for this disease.

PMID- 12064511
TI  - Multinodular goiter: surgical management and histopathological findings.
AB  - The purpose of this study was to assess histopathological findings after a
      bilateral near-total thyroidectomy (residual thyroid tissue about 4 to 5 g) for
      multinodular goiter (MNG). The 270 patients included 238 women and 32 men with a
      mean age of 52 years (range: 19-82 years) who had MNG involving the entire gland
      and had undergone a primary bilateral surgical procedure between 1993-1998. There
      was no intra- or postoperative mortality. Indications for the MNG surgery were
      suspected malignancy (7.7%), thyrotoxicosis (27.7%), pressure on cervical
      structures with tracheal deviation (38%), significant cosmetic deformity in young
      female patients (6.6%) and intrathoracic extension of the MNG (19.6%). Grave's
      disease was not included in our study. The surgical specimen weight ranged from
      60 to 560 g (average 120 g). Final pathological findings were benign in 237
      patients (87.8%) and malignant in 33 patients (12.2%). Nineteen patients were
      diagnosed with macroscopic (ten patients) or microscopic (nine patients) types of
      papillary carcinoma: there were two patients with the follicular variant of
      papillary carcinoma, three with lymphoma and Hashimoto's thyroiditis, three with
      medullar carcinoma, three with anaplastic carcinoma, two with follicular
      carcinoma and one with Hurthle cell carcinoma. A true total completion
      thyroidectomy was performed only for the medullary carcinoma patients and for
      four of the "high-risk" papillary carcinoma patients. Permanent (>12 months)
      unilateral recurrent paralysis occurred in four patients (1.4%), permanent (>12
      months) hypoparathyroidism in ten patients (3.7%) and hypertrophic or keloid scar
      in 14 patients (5.1%). Our results suggest that near total thyroidectomy with
      minimal residual tissue is a versatile surgical procedure for various
      histopathological features in MNG patients. Low rates of postoperative
      complications were observed.

PMID- 12064512
TI  - Reduction of neuronal and inducible nitric oxide synthase gene expression in
      patients with cystic fibrosis.
AB  - As a consequence of diminished nitric oxide synthase (NOS) protein concentration,
      the airway concentration of nitric oxide (NO) is reduced in patients with cystic
      fibrosis (CF). This appears to lead to a reduced elimination of such
      microorganisms as Pseudomonas aeruginosa. The objective of this study was to
      analyze whether inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) NOS are
      reduced at mRNA level and if so whether this is caused directly by the defective
      CF transmembrane conductance regulator (CFTR). Nasal polyps from three patients
      with CF and four otherwise healthy patients were obtained. The expression of the
      three NOS isoenzymes was quantified using real-time PCR. The iNOS expression was
      assessed in colon carcinoma cells (CaCo) transfected with a normal and a mutated
      (DeltaF508) CFTR. In CF patients, iNOS mRNA expression was 10-to 20-fold and bNOS
      gene expression was one-fifth to one-tenth that in control patients (P < 0.001).
      In CaCo cells, iNOS gene expression under basal and endotoxin-stimulated
      conditions did not differ between cells transfected with a mutated CFTR and those
      transfected with an intact CFTR. This observation suggests that cystic fibrosis
      is associated with reduced iNOS and bNOS gene expression in nasopharyngeal
      tissue, possibly disturbing the barrier against infective agents already at the
      site of entrance.

PMID- 12064513
TI  - Reserpine: interactions with batrachotoxin and brevetoxin sites on voltage
      dependent sodium channels.
AB  - Reserpine inhibited batrachotoxin-elicited sodium influx in guinea pig brain
      synaptoneurosomes with an IC50 of about 1 microM. In the presence of brevetoxin
      the IC50 increased to about 80 microM. Reserpine inhibited binding of
      batrachotoxinin-A [3H]benzoate ([3H]BTX-B) binding in a complex manner causing a
      partial inhibition from 0.001 to 0.08 microM, then a rebound stimulation from 0.1
      to 0.8 microM, followed by complete inhibition by 80 microM. The stimulation was
      prevented by the presence of brevetoxin; reserpine then smoothly inhibited
      binding with an IC50 of about 1 microM. Reserpine at 1 microM slightly reduced
      the off-rate of [3H]BTX-B binding measured in the presence of veratridine, while
      at a concentration of 50 microM it enhanced the off-rate, presumably by an
      allosteric mechanism. Reserpine at 0.3-10 microM elicited a partial inhibition of
      the binding of [3H]brevetoxin-3. The local anesthetic dibucaine had effects
      similar to reserpine: It partially inhibited binding of [3H]brevetoxin. The
      presence of brevetoxin reduced the potency of dibucaine as an inhibitor of
      batrachotoxin-elicited sodium influx from an IC50 of about 2 microM to an IC50 of
      about 50 microM. The results suggest that reserpine binds at both a local
      anesthetic site to cause allosteric inhibition of batrachotoxin-binding and
      action, but that it also binds to another site causing, like brevetoxin, an
      enhancement of batrachotoxin-binding and action. Local anesthetics also may bind
      to the brevetoxin site.

PMID- 12064514
TI  - Dephosphorylation of tau protein by calcineurin triturated into neural living
      cells.
AB  - Alzheimer disease and related dementia are characterized by the presence of
      hyperphosphorylated tau aggregated into filaments. The role of tau
      phosphorylation in the fibrillogenesis has not yet been unraveled. Therefore, it
      is important to know which phosphatases can dephosphorylate tau protein in vivo.
      The effect of recombinant purified calcineurin (CN(PP2B)) and several calcineurin
      mutants on tau phosphorylation was studied in two neuronal like cell lines PC12
      and SH-SY5Y. The modulation of tau phosphorylation at Serl99/Ser202,
      Ser396/Ser404, Ser262/Ser356, and Thr181 sites was examined in these cell lines
      using the phosphorylation state-dependent antitau antibodies Tau 1, PHF1, 12E8,
      and AT270. The results have shown that CN directly dephosphorylates all of those
      sites of tau protein. Recombinant calcineurin introduced into cells that have
      previously been treated with okadaic acid and cyclosporin A, which are inhibitors
      of phosphatases (PP1/PP2A and PP2B), has a direct effect on the phosphorylation
      status on all phosphorylation sites studied. We conclude that calcineurin is
      (besides PP2A) a important modulator of tau phosphorylation in vivo.

PMID- 12064515
TI  - Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in
      adulthood: implications for genesis of autism and schizophrenia.
AB  - We investigated the role of maternal exposure to human influenza virus (H1N1) in
      C57BL/6 mice on Day 9 of pregnancy on pyramidal and nonpyramidal cell density,
      pyramidal nuclear area, and overall brain size in Day 0 neonates and 14-week-old
      progeny and compared them to sham-infected cohorts. Pyramidal cell density
      increased significantly (p < 0.0038) by 170% in Day 0 infected mice vs. controls.
      Nonpyramidal cell density decreased by 33% in Day 0 infected progeny vs. controls
      albeit, nonsignificantly. Pyramidal cell nuclear size decreased significantly (p
      < 0.0465) by 29% in exposed newborn mice vs. controls. Fourteen-week-old exposed
      mice continued to show significant increases in both pyramidal and nonpyramidal
      cell density values vs. controls respectively (p < 0.0085 E1 (exposed group 1), p
      < 0.0279 E2 (exposed group 2) pyramidal cell density; p < 0.0092 E1, p < 0.0252
      E2, nonpyramidal cell density). By the same token, pyramidal cell nuclear size
      exhibited 37-43% reductions when compared to control values; these were
      statistically significant vs. controls (p < 0.04 E1, p < 0.0259 E2). Brain and
      ventricular area measurements in adult exposed mice also showed significant
      increases and decreases respectively vs. controls. Ventricular brain ratios
      exhibited 38-50% decreases in exposed mice vs. controls. While the rate of
      pyramidal cell proliferation per unit area decreased from birth to adulthood in
      both control and exposed groups, nonpyramidal cell growth rate increased only in
      the exposed adult mice. These data show for the first time that prenatal exposure
      of pregnant mice on Day 9 of pregnancy to a sublethal intranasal administration
      of influenza virus has both short-term and long-lasting deleterious effects on
      developing brain structure in the progeny as evident by altered pyramidal and
      nonpyramidal cell density values; atrophy of pyramidal cells despite normal cell
      proliferation rate and final enlargement of brain. Moreover, abnormal
      corticogenesis is associated with development of abnormal behavior in the exposed
      adult mice.

PMID- 12064516
TI  - Cell swelling induced secretion of TRH by posterior pituitary, hypothalamic
      paraventricular nucleus and pancreatic islets: effect of L-canavanine.
AB  - The aims of this study were to test if ethanol induces thyrotropin-releasing
      hormone (TRH) secretion in vitro from the posterior pituitary and hypothalamic
      explants by a mechanism involving cell swelling, and to characterize the pathway
      of stimulated secretion. Ethanol, at a concentration of 80 mM, stimulated the
      release of TRH from the posterior pituitary, the hypothalamic paraventricular
      nucleus, the median eminence, and the brain septum, when administered only in
      isosmolar but not in hyperosmolar medium. This indicates the involvement of a
      cell swelling-inducing mechanism. L-canavanine in a concentration of 3 mM,
      increased the basal and hyposmosis-induced TRH secretion from the posterior
      pituitary and the paraventricular nucleus, and both basal and ethanol-induced TRH
      secretion from isolated pancreatic islets. This indicates the presence of both
      constitutive and regulatory secretory pathways. Our results suggest that cell
      swelling induces exocytosis from clathrin coated granules.

PMID- 12064517
TI  - Coupling of dopamine receptors to G proteins: studies with chimeric D2/D3
      dopamine receptors.
AB  - D2 and D3 dopamine receptors belong to the superfamily of G protein-coupled
      receptors; they share a high degree of homology and are structurally similar.
      However, they differ from each other in their second messenger coupling
      properties. Previously, we have studied the differential coupling of these
      receptors to G proteins and found that while D2 receptor couples only to
      inhibitory G proteins, D3 receptor couples also to a stimulatory G protein, Gs.
      We aimed to investigate the molecular basis of these differences and to determine
      which domains in the receptor control its coupling to G proteins. For this
      purpose four chimeras were constructed, each composed of different segments of
      the original D2 and D3 receptors. We have demonstrated that chimeras with a third
      cytoplasmic loop of D2 receptor couple to Gi protein in a pattern characteristic
      of D2 receptor. On the other hand chimeras containing a third cytoplasmic loop of
      D3 receptor have coupling characteristics like those of D3 receptor, and they
      couple also to Gs protein. These findings demonstrate that the third cytoplasmic
      loop determines and accounts for the coupling of dopamine receptors D2 and D3 to
      G proteins.

PMID- 12064518
TI  - A cytological study on the development of the different types of visual cells in
      the chicken (Gallus domesticus).
AB  - The formation of visual cells and their intracellular organelles was studied in
      the embryonic chicken (Gallus domesticus) between stage 36 and hatching. Cilia
      formation was observed at stage 30 and by stage 42, outer segment formation from
      the cilia was evident. The inner segments appeared as buddings at stage 36. By
      stage 37, the buddings of double cones were observed clearly and such buddings
      elongated by stage 42. Both the single cones and rods appeared as buddings by
      stage 38 and elongation of the buddings was seen by stage 42. Oil droplets
      initially appeared by stage 39 in accessory cones and were observed in other
      cones by stage 42. Glycogen bodies were demonstrated firstly in rods and
      accessory cones at stage 43 and their development was completed by stage 45. In
      essence, all the essential elements of the visual cells were fully developed by
      hatching.

PMID- 12064519
TI  - Pyruvate blocks zinc-induced neurotoxicity in immortalized hypothalamic neurons.
AB  - Zinc is an essential trace element and present at high concentrations in the
      central nervous system. Recent studies have revealed that excess amount of
      extracellular zinc is neurotoxic, and that the disruption of zinc homeostasis may
      be related to various neurodegenerative diseases. Zinc (25-100 microM) caused
      significant death of immortalized hypothalamic neuronal cells (GT1-7 cells) in a
      dose- and time-dependent manner. LD50 was estimated to be 34 microM. The
      degenerated cells were TUNEL-positive and exhibited apoptosis-like
      characteristics. Preadministration of sodium pyruvate (1-2 mM), a downstream
      energy substrate, inhibited the zinc-induced neurotoxicity in GT1-7 cells. GT1-7
      cells can be used as a good tool for the investigation of zinc neurotoxicity in
      the hypothalamus.

PMID- 12064520
TI  - Differentiation of embryonic stem cell to astrocytes visualized by green
      fluorescent protein.
AB  - Green fluorescent protein (GFP) gene was transfected and expressed in murine
      embryonic stem (ES) cells under the control of the astrocyte-specific glial
      fibrillary acidic protein (GFAP) promoter. Stably transfected cells were
      characterized by immunohistochemistry and by fluorescence microscopy. Cells
      containing GFP were differentiated to Type I and Type II astrocytes after
      induction by all-trans retinoic acid. Differentiated cells were expressed GFP and
      visualized by fluorescence microscopy. Differentiated cells expressed GFP were
      correlated with the expression of GFAP and morphological change. It demonstrates
      that the cell line expressed GFP can be used to trace the morphological changes
      of astrocytes during differentiation, and further for the isolation of astrocytes
      from the mixed cells differentiated from ES cell.

PMID- 12064521
TI  - Modified aluminas as chromatographic supports for high-performance liquid
      chromatography.
AB  - This review begins by describing the relevant properties of alumina as a support
      material for chemically bonded stationary phases in HPLC. The most common
      chemical modification processes are summarized as well as the advantages and
      disadvantages of each method. In order to more fully understand the chemically
      modified alumina surface, some spectroscopic approaches are outlined for
      characterization of the bonded phases. Finally, a number of successful
      applications are described for a variety of chemically modified aluminas in order
      to illustrate their potential usefulness and to compare their chromatographic
      behavior to the more conventional silica-based materials.

PMID- 12064522
TI  - Quantification of veterinary antibiotics (sulfonamides and trimethoprim) in
      animal manure by liquid chromatography-mass spectrometry.
AB  - A fast and cost effective method was developed to extract and quantify residues
      of veterinary antimicrobial agents (antibiotics) in animal manure by liquid
      liquid extraction and liquid chromatography-mass spectrometry. The compounds
      investigated include six sulfonamides, one metabolite, and trimethoprim. The
      method was performed without sample clean up. Recoveries from spiked manure
      slurry samples (spike level = 1 mg/kg) were as follows: sulfaguanidine (52%),
      sulfadiazine (47%), sulfathiazole (64%), sulfamethazine (89%), its metabolite N4
      acetyl-sulfamethazine (88%), sulfamethoxazole (84%), sulfadimethoxine (51%), and
      trimethoprim (64%). Relative standard deviations of the recoveries were less than
      5% within the same day and less than 20% between days. The limit of
      quantification was below 0.1 mg/kg liquid manure slurry for all compounds and
      calibration curves obtained from extracts of spiked samples were linear up to a
      level of 5 mg/kg liquid manure, except for trimethoprim (0.01-0.5 mg/kg).
      Analysis of six grab samples taken in Switzerland from manure pits on farms where
      medicinal feed had been applied revealed total sulfonamide concentrations of up
      to 20 mg/kg liquid manure.

PMID- 12064524
TI  - Protein separation using membrane chromatography: opportunities and challenges.
AB  - Some of the problems associated with packed bed chromatography can be overcome by
      using synthetic macroporous and microporous membranes as chromatographic media.
      This paper reviews the current state of development in the area of membrane
      chromatographic separation of proteins. The transport phenomenon of membrane
      chromatography is briefly discussed and work done in this area is reviewed. The
      various separation chemistries which have been utilised for protein separation,
      along with different applications, are also reviewed. The technical challenges
      facing membrane chromatography are highlighted and the scope for future work is
      discussed.

PMID- 12064523
TI  - Multiresidue determination of (fluoro)quinolone antibiotics in swine kidney using
      liquid chromatography-tandem mass spectrometry.
AB  - New antibiotics were recently developed, among which are the (fluoro)quinolones.
      This paper presents an analytical method which allows the determination of 11
      (fluoro)quinolones in swine kidneys: norfloxacin, ofloxacin, cinoxacin, oxolinic
      acid, nalidixic acid, flumequine, enrofloxacin, enoxacin, ciprofloxacin,
      danofloxacin and marbofloxacin. The procedure involves a rapid and efficient pre
      treatment by solid-phase extraction (recoveries 83-98%), followed by the
      sensitive and selective determination of all compounds in a single run using LC
      ESI-MS-MS. Multiple reaction monitoring (MRM) was used for selective detection of
      each (fluoro)quinolone. Quinine was selected as internal standard. The accuracy
      of the method, expressed as recovery, was between 89 and 109%; the repeatability
      had a maximum RSD lower than 15%. The limits of detection (LOD) were much lower
      than the respective Maximum Residue Limits (MRL)/4.

PMID- 12064525
TI  - Chemiluminescence detection coupled to high-performance frontal analysis for the
      determination of unbound concentrations of drugs in protein binding equilibrium.
AB  - High-performance frontal analysis coupled with chemiluminescence detection (HPFA
      CL) was developed for the determination of unbound oxacillin concentration in
      human serum albumin solution. The HPFA system consisted of an ISRP column and a
      mobile phase of 67 mM potassium phosphate buffer of pH 7.4 and ionic strength of
      0.17. The luminol-H2O2-Co2+ system was used in the chemiluminescence detection.
      An enhancement of luminol chemiluminescence by oxacillin was investigated and
      employed for determining the concentration of oxacillin in the HPFA eluate.
      Sample solutions were directly injected onto the column; the drug was eluted as a
      zonal peak with a plateau region. The unbound drug concentrations were determined
      by using the height of the plateau. The results agreed with those obtained with
      conventional ultrafiltration-HPLC method. Good reproducibility was confirmed by
      the within run and between run RSD < or = 7.4%. HPFA-CL provided a selective
      method for determination of unbound drug concentration in protein binding
      equilibrium.

PMID- 12064526
TI  - Analysis of acidic drugs in the effluents of sewage treatment plants using liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - A liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI
      MS-MS) method was developed and validated for simultaneous analysis of nine
      acidic pharmaceutical drugs (bezafibrate, clofibric acid, diclofenac, fenoprofen,
      gemfibrozil, ibuprofen, indomethacin, ketoprofen and naproxen) in sewage
      treatment plant (STP) effluents. The mean recoveries of the pharmaceuticals
      ranged from 58.9 to 91.5% in STP effluent, and the limits of detection of the
      analytes were 5-20 ng/ml. The method was applied to the quantitative analysis of
      acidic drugs in the effluents from three Canadian STPs, in which bezafibrate,
      diclofenac, fenoprofen, gemfibrozil, ibuprofen, indomethacin and naproxen were
      detected.

PMID- 12064527
TI  - Liquid exclusion-adsorption chromatography, a new technique for isocratic
      separation of nonionic surfactants. IV. Two-dimensional separation of fatty
      alcohol ethoxylates with focusing of fractions.
AB  - Fatty alcohol ethoxylates can be analyzed using a combination of liquid
      chromatography under critical conditions as the first dimension and liquid
      exclusion-adsorption chromatography as the second dimension. Transfer of
      fractions from the first to the second dimension is achieved using the full
      adsorption-desorption (FAD) technique. The peaks of interest in the first
      dimension are trapped on a short precolumn before injecting them into the second
      dimension. Full adsorption is achieved by increasing the water content in the
      mobile phase before the FAD column. When the fractions are desorbed by switching
      to the mobile phase of the second dimension, they are focused and reconcentrated.
      In this way, a full resolution of oligomers is achieved. As both dimensions are
      run in isocratic mode, density and refractive index detection can be applied,
      which allows an accurate quantitation.

PMID- 12064528
TI  - Determination of alkyl benzyl and dialkyl dimethyl quaternary ammonium biocides
      in occupational hygiene and environmental media by liquid chromatography with
      electrospray ionisation mass spectrometry and tandem mass spectrometry.
AB  - A new method for the simultaneous qualitative and quantitative determination of
      alkyl benzyl and dialkyl quaternary ammonium compounds (QACs) has been developed.
      Analysis is by reversed-phase high-performance liquid chromatography coupled with
      electrospray ionisation mass spectrometry. QACs are extremely amenable to the
      electrospray ionisation technique (limit of detection of BAC C12 homologue 3 ng
      ml(-1)). The selectivity of mass spectrometric detection allows simultaneous
      determination of benzyl and dialkyl dimethyl ammonium compounds. The method was
      successfully applied to the analysis of real samples (occupational hygiene
      sampling devices, products and swimming pool water). Structural information was
      obtained by MS-MS and cone voltage ion dissociation techniques. Ion dissociation
      enabled the structural elucidation of an unknown quaternary ammonium compound
      present in a commercial formulation.

PMID- 12064529
TI  - Electron-capture detector and multiple negative ions of aromatic hydrocarbons.
AB  - Multiple electron affinities are identified in the temperature dependence of the
      electron-capture detector: naphthalene, 0.16, 0.13+/-0.01, anthracene, 0.69,
      0.60, 0 53+/-0.01; tetracene 1.1, 0.88+/-0.03, 0.53+/-0.05; pyrene, 0.61, 0.50+/
      0.02; azulene 0.90, 0.80, 0.70+/-0.02, 0.65, 0.55+/-0.05; acenaphthylene, 0.80,
      0.69, 0.60, 0.50+/-0.05; and c-C8H8, 0.80, 0.70, 0.55+/-0.02; (all in eV). These
      are obtained from a rigorous least squares procedure incorporating literature
      values and uncertainties. The adiabatic electron affinities for about 40
      hydrocarbons listed in the US National Institute of Standards and Technology
      (NIST) tables are evaluated. The adiabatic electron affinity values not listed in
      NIST are biphenylene, 0.45+/-0.05 eV and coronene. 0.8+/-0.05 eV. Morse potential
      energy curves in the C-H dimensions illustrate multiple states for benzene and
      naphthalene.

PMID- 12064530
TI  - Sensitive method for the determination of 1,3-dichloropropan-2-ol and 3
      chloropropane-1,2-diol in soy sauce by capillary gas chromatography with mass
      spectrometric detection.
AB  - This paper reports the development of a highly selective and sensitive method for
      the determination of parts-per-billion level of 1,3-dichloropropan-2-ol (1,3-DCP)
      and 3-chloropropane-1,2-diol (3-MCPD) in soy sauce using capillary gas
      chromatography with mass spectrometric detection. Samples were homogenised, mixed
      with sodium chloride solution and then adsorbed on silica gel. The loaded silica
      gel was packed into a chromatographic column, from which chloropropanols were
      extracted by elution with ethyl acetate. Heptafluorobutyric acid anhydride was
      added to the concentrated eluant to derivatise the chloropropanols and the
      derivatised analytes were separated by gas chromatography, identified and
      quantified by mass spectrometry. A linear relationship between the concentration
      of the two chloropropanols and the detector response was obtained over the
      concentration range of 10-1000 microg/kg. Precision of the method was
      satisfactory at about 5%, and recoveries of 1,3-DCP and 3-MCPD from soy sauce
      samples spiked at 25 microg/kg were 77 and 98%, respectively. The limit of
      quantitation of the method was found to be about 5 microg/kg for 1,3-DCP and 3
      MCPD, respectively meeting the requirements of tolerance limits adopted by
      different international institutions and governments around the world. This paper
      is the first of its kind in reporting an analytical procedure for the
      simultaneous separation and determination of 3-MCPD and 1,3-DCP, a more potent
      contaminant, at low microg/kg level.

PMID- 12064531
TI  - Systematic characterisation of long-chain aliphatic esters of wool wax by gas
      chromatography-electron impact ionisation mass spectrometry.
AB  - A detailed structural characterisation of the aliphatic high-molecular-mass
      esters extracted from raw wool based on high-temperature gas chromatography
      electron impact ionisation mass spectrometry is described. The raw wool esters
      extracted are in the range of C37 to C54 (i.e., molecular mass 550-788). The
      selected ion chromatogram exhibited four isomers for the esters with an odd
      number of carbon atoms (i:a, i:n, a:n and n:n) and five for those with an even
      number of carbon atoms (i:i, a:a, i:n, a:n and n:n). Isomeric structural
      elucidation is discussed with respect to the long-chain fatty acid and long-chain
      fatty alcohol structures, on the basis of chromatographic retention behaviour and
      mass spectral information.

PMID- 12064532
TI  - Formation of 2-chlorobenzylidenemalononitrile (CS riot control agent) thermal
      degradation products at elevated temperatures.
AB  - 2-Chlorobenzylidenemalononitrile (CS riot control agent) has been shown to
      produce a number of thermal degradation products when dispersed at high
      temperature. We hypothesized that these CS-derived compounds are formed by energy
      input from heating during the dispersion process. Here we identified organic CS
      derived compounds formed from purified CS subjected to temperatures ranging from
      300 to 900 degrees C in an inert atmosphere with analysis of tube furnace
      effluent by gas chromatography and mass spectrometry. We conclude that the
      production of many CS-derived compounds previously observed during high
      temperature dispersion is likely to be heat related.

PMID- 12064533
TI  - Analysis of antifouling biocides Irgarol 1051 and Sea Nine 211 in environmental
      water samples using solid-phase microextraction and gas chromatography.
AB  - This study develops a method for the analysis of biocides Irgarol 1051 and Sea
      Nine 211 in environmental water samples, using solid-phase microextraction
      (SPME). Their determination was carried out using gas chromatography with flame
      thermionic (FTD), electron-capture (ECD) and mass spectrometric detection. The
      main parameters affecting the SPME process such as adsorption-time profile, salt
      additives and memory effect were studied for five polymeric coatings commercially
      available for solid-phase microextraction: poly(dimethylsiloxane) (100 and 30
      microm), polyacrylate, poly(dimethylsiloxane)-divinylbenzene (PDMS-DVB 65 microm)
      and Carbowax-divinylbenzene (65 microm). The method was developed using spiked
      natural waters such as tap, river, sea and lake water in a concentration range of
      0.5-50 microg/l. All the tested fiber coatings have been evaluated with regard to
      sensitivity, linear range, precision and limits of detection. Typical RSD values
      (triplicate analysis) in the range of 3-10% were obtained depending on the fiber
      coating and the compound investigated. The recoveries of biocides were in
      relatively high levels 60-118% and the calibration curves were reproducible and
      linear (R2>0.990) for both analytes. The SPME partition coefficients (Kf) of both
      compounds were also calculated experimentally in the proposed conditions for all
      fibers using direct sampling. Finally the influence of organic matter such as
      humic acids on extraction efficiency was studied, affecting mostly Sea Nine 211
      uptake by the fiber. Optimum analytical SPME performance was achieved using the
      PDMS-DVB 65 microm fiber coating in ECD and FTD systems for Sea Nine 211 and
      Irgarol 1051, respectively.

PMID- 12064534
TI  - Determination of phosphine in biogas and sludge at ppt-levels with gas
      chromatography-thermionic specific detection.
AB  - A gas chromatographic (GC) system to measure free phosphine in biogas and matrix
      bound phosphine in manure and sludge is presented. The system consists of a
      sample preconcentration trap filled with glass beads, connected with a capillary
      GC equipped with a thermionic specific detector. With a trap temperature as low
      as -155 degrees C, a sampling flow of 20 ml/min and a typical total sample volume
      of 100 ml, free phosphine concentrations in the low ng/m3 range and matrix bound
      phosphine in the low ng/kg dry matter range, can be accurately and reproducibly
      determined.

PMID- 12064535
TI  - Kinetic study of the polymerization of alpha-amino acid N-carboxyanhydrides in
      aqueous solution using capillary electrophoresis.
AB  - N-Carboxyanhydrides of amino acids (NCAs) are very reactive monomers able to
      polymerize into oligopeptides. They are assumed to be prebiotic precursors of the
      first polypeptides. Few reports have been published on the study of NCA
      polymerization in aqueous solution. In this work, a kinetic study focused on the
      hydrolysis of NCA and its coupling with amino acids and homopeptides (up to
      tripeptide) was carried out, taking L-valine derivatives as model compounds. For
      that purpose, capillary electrophoresis appeared to be an effective and reliable
      technique for the measurement of the kinetic constants. The electrophoretic
      separation conditions, the procedure for stopping NCA reactivity, as well as the
      conditions of reaction are discussed in detail. We report the variation of the
      kinetic constant of the coupling reaction of the NCA of valine with an
      oligovaline as a function of its degree of polymerization. Finally, a temperature
      study also allowed us to estimate the activation energies associated with the NCA
      of valine hydrolysis and its coupling reaction with valine.

PMID- 12064536
TI  - Capillary electrophoresis-electrochemistry microfluidic system for the
      determination of organic peroxides.
AB  - A microfluidic analytical system for the separation and detection of organic
      peroxides, based on a microchip capillary electrophoresis device with an
      integrated amperometric detector, was developed. The new microsystem relies on
      the reductive detection of both organic acid peroxides and hydroperoxides at -700
      mV (vs. Ag wire/AgCl). Factors influencing the separation and detection processes
      were examined and optimized. The integrated microsystem offers rapid measurements
      (within 130 s) of these organic-peroxide compounds, down to micromolar levels. A
      highly stable response for repetitive injections (RSD 0.35-3.12%; n = 12)
      reflects the negligible electrode passivation. Such a "lab-on-a-chip" device
      should be attractive for on-site analysis of organic peroxides, as desired for
      environmental screening and industrial monitoring.

PMID- 12064537
TI  - Electroosmotic flow controllable coating on a capillary surface by a sol-gel
      process for capillary electrophoresis.
AB  - A simple coating procedure employing a sol-gel process to modify the inner
      surface of a bare fused-silica capillary with a positively charged quaternary
      ammonium group is established. Scanning electron microscopic studies reveal that
      a smooth coating with 1 to approximately 2 microm thickness can be obtained at
      optimized coating conditions. With 40 mM citrate as a running electrolyte, the
      plot of electroosmotic flow (EOF) versus pH shows a unique three-stage EOF
      pattern from negative to zero and then to positive over a pH range of 2.5 to 7.0.
      At pH above 5.5, the direction of the EOF is from the anode to the cathode, as is
      the case in a bare fused-silica capillary, and the electroosmotic mobility
      increases as the pH increases. However, the direction of the EOF is reversed at
      pH below 4.0. Over the pH range of 4.0 to 5.5, zero electroosmotic mobility is
      obtained. Such a three-stage EOF pattern has been used to separate six aromatic
      acids under suppressed EOF and to separate nitrate and nitrite with the anions
      migrating in the same direction as the EOF. The positively charged quaternary
      ammonium group on the coating was also utilized to minimize the adsorption
      problem during the separation of five basic drugs under suppressed EOF and during
      the separation of four basic proteins with the cations migrate in the opposite
      direction as the EOF. Also, the stability and reproducibility of this column are
      good.

PMID- 12064538
TI  - Cycloaliphatic epoxy resin coating for capillary electrophoresis.
AB  - Coating the interior surface of a fused-silica capillary with a polymeric
      material has long been used in capillary electrophoresis (CE) to reduce or
      eliminate electroosmotic flow and suppress adsorption. A cycloaliphatic epoxide
      based resin was bonded to silane treated capillaries and crosslinked with a
      curing agent. The epoxy resin coating significantly reduced electroosmotic flow
      over a pH range of 3-10. This coating was sufficiently hydrophilic to suppress
      protein adsorption. The epoxy resin coated capillary was used to separate several
      acidic and basic proteins and peptides. Separation efficiencies greater than
      400,000 theoretical plates were achieved. The relative standard deviations in
      migration times for proteins were <0.8%. Speed and simplicity are important
      advantages of the coating procedure compared to other published coating methods.

PMID- 12064539
TI  - Fast, efficient capillary electrophoresis method for measuring nucleotide
      degradation and metabolism.
AB  - An easy and fast method for the quantitative analysis of nucleotides by capillary
      zone electrophoresis was developed. The method employing a neutral-bonded
      capillary and reversed polarity mode provided a good resolution and a short
      analysis time of less than 5 min. The samples were injected electrokinetically
      using -6 kV voltage for 30 s and detected by their UV absorbance at 254 nm.
      Constant current (-45 microA) was applied, and a phosphate buffer, pH 7.4, was
      used. The detection limits for ATP, UDP, and UTP ranged between 0.14 and 0.28
      microM. This method was required for the investigation of the purity of the
      commercially available nucleotides used in pharmacological studies. In addition,
      the analytical method was applied to study the metabolism of nucleotides in a
      cell line, neuroblastoma x glioma hybrid cells (NG108-15), which is used in
      pharmacological studies with nucleotides, since it contains purine- and
      pyrimidine-sensitive nucleotide receptors. Furthermore, we used the new method
      for monitoring enzymatic studies using the enzyme hexokinase to convert
      nucleotide triphosphates to diphosphates.

PMID- 12064540
TI  - Determination of etoposide phosphate intermediates by gradient liquid
      chromatography using postcolumn derivatization with cuprammonium hydroxide.
AB  - Allyl 4,6-O-ethylidene-beta-D-glucopyranoside is an intermediate used in the
      synthesis of etoposide phosphate, a water-soluble derivative of the
      antineoplastic drug etoposide. In this paper, a method for the determination of
      allyl 4,6-O-ethylidene-beta-D-glucopyranoside and related glucopyranosides is
      described. Samples are analyzed by gradient high-performance liquid
      chromatography using postcolumn derivatization with cuprammonium hydroxide. The
      method is used to monitor the ethylidenation reaction of allyl beta-D
      glucopyranoside with acetal to form allyl 4,6-O-ethylidene-beta-D
      glucopyranoside. Samples are chromatographed on an octadecyl-bonded phase column
      with aqueous acetonitrile. Triethylamine is added to the mobile phase to
      accelerate mutarotation and suppress anomeric separations. The column effluent is
      mixed via a postcolumn tee with cuprammonium hydroxide and monitored with
      ultraviolet detection at 310 nm.

PMID- 12064541
TI  - Evaluation of liquid chromatography-negative ion electrospray mass spectrometry
      for the determination of selected resin acids in river water.
AB  - A liquid chromatography-negative ion electrospray mass spectrometric (LC-ESI-MS)
      method was evaluated for detection of four prevalent softwood-derived resin acids
      in natural water. Method detection limits based on a signal-to-noise ratio of 3:1
      in river water samples of 0.40, 0.40, 0.30 and 0.25 microg l(-1) for abietic,
      dehydroabietic, isopimaric and pimaric acids, respectively, are comparable or
      lower than reported GC methods. Unlike the majority of GC methods, however, the
      three structural resin acid isomers (abietic, isopimaric and pimaric acids) do
      not separate sufficiently under the various LC conditions evaluated in this work.
      Therefore, LC-ESI-MS may not be suitable for instances where measurement of
      individual isomeric resin acids is required. However, the method is suitable for
      trace analysis of resin acids in natural waters where isomeric speciation is not
      required.

PMID- 12064542
TI  - Investigations on factors that influence the moving neutralization reaction
      boundary method for capillary electrophoresis and isoelectric focusing.
AB  - We investigated several factors, such as temperature, current intensity (i), time
      (t) and the product (mA min mm(-2), viz., C mm(-2)) of i and t, etc., that
      obviously affect the moving neutralization reaction boundary method (MNRBM). The
      results manifest that the temperature and the product ti have a strong influence
      on the movement rate of the boundary. The data prove that about 0.6 C mm(-2)
      (being equivalent to 10 mA min mm(-2)) is a critical point. If the product ti is
      lower than the critical point, a good quantitative agreement exists between the
      observed and theoretical values, but if it is higher than the critical point, the
      agreements are poor. The optimized experimental conditions are: (1) 18-20 degrees
      C room temperature, (2) 0.6-0.8 mA mm(-2), (3) less than 10 mA min mm(-2), (4) 1%
      agarose gel, (5) daily prepared solution and gel containing NaOH. The optimized
      MNRBM is of benefit for the studies on MNRB itself, isoelectric focusing and
      capillary zone electrophoresis as will be partially shown in this paper.

PMID- 12064543
TI  - Lipophilicity of a series of 1,2-benzisothiazol-3(2H)-ones determined by reversed
      phase thin-layer chromatography.
AB  - The lipophilicity (R(Mo)) and specific hydrophobic surface area of seven 1,2
      benzisothiazol-3(2H)-ones have been determined by reversed-phase TLC and the
      effect of different mobile-phase modifiers (acetone, acetonitrile, methanol) on
      the retention has been studied. The linear correlations between the volume
      fraction of the organic solvent and the R(M) values over a limited range were
      established for each solute with high values of correlation coefficients (>0.99).
      The influence of solvent pH on R(M) values was investigated.

PMID- 12064544
TI  - Improving separation efficiency of capillary zone electrophoresis of tryptophan
      and phenylalanine with the transient moving chemical reaction boundary method.
AB  - A simple and convenient mode--moving chemical reaction boundary method-capillary
      zone electrophoresis (MCRBM-CZE)--was designed for the enhancement of separating
      efficiency of CZE. In this mode, the transient MCRBM is used for the on-line pre
      treatment of sample. By analyses of tryptophan (Trp) and phenylalanine (Phe) as
      an example, the experiments by MCRBM-CZE were carried out and further compared
      with those by normal CZE without the transient MCRBM. The results reveal that by
      carefully selected appropriate electrolytes, a strong condensation effect can be
      achieved by using MCRBM-CZE; this effect can greatly improve the separation
      efficiency, resolution and peak height of Trp and Phe in CZE as compared with
      those of normal CZE of Trp and Phe. Even if the sample comprises high
      concentrations of salt, such as 80 mM NaCl (concentration of sodium ion up to
      145.6 mM), the same condensation effect can also been observed; this implies
      obvious significance for biological samples like urine and serum. However, if the
      electrolytes was chosen inappropriately only a poor compression effect of sample
      was observed in the MCRBM-CZE runs.

PMID- 12064545
TI  - Method for measuring the logarithm of the octanol-water partition coefficient by
      using short octadecyl-poly(vinyl alcohol) high-performance liquid chromatography
      columns.
AB  - A simple, quick, versatile and inexpensive HPLC method to estimate the logarithm
      of the octanol-water partition coefficient (log Pow) employing a methanol-water
      gradient and a short octadecyl-poly(vinyl alcohol) (ODP) column is described.
      This method is different from published HPLC-based log Pow methods because it
      uses retention times from a rapid methanol-water gradient to directly generate
      log Pow estimates, rather than from a series of isocratic mixtures extrapolated
      to 100% water. These HPLC log Pow values have good precision and correlate well
      with traditional shake-flask log Pow values. If necessary, the log Pow
      determination (including replications) can easily be carried out using only a
      milligram of sample. By suppressing ionization of acids and bases by the use of a
      buffer in the aqueous phase, the method can measure the log Pow of neutral
      organic molecules at any pH between 2 and 13. The method can be used with impure
      material and is rapid, 7 min per run and 4 min equilibration; it lends itself to
      and has been utilized for high-throughput hydrophobicity determinations (we have
      now carried out thousands of HPLC log Pow measurements by this method).

PMID- 12064546
TI  - Comparison of the capability of peak functions in describing real chromatographic
      peaks.
AB  - This paper describes the results of a comparison of four peak functions in
      describing real chromatographic peaks. They are the empirically transformed
      Gaussian, polynomial modified Gaussian, generalized exponentially modified
      Gaussian and hybrid function of Gaussian and truncated exponential functions.
      Real chromatographic peaks of different shapes (fronting. symmetric, and tailing)
      are obtained by various separation conditions of reversed-phase liquid
      chromatography. They are then fitted to the peak functions via the Marquardt
      Levenberg algorithm, a nonlinear least-squares curve-fitting procedure, by
      Microsoft Solver. The qualities of the fits are evaluated by the sum of the
      squares of the residuals. It is concluded in the study that the empirically
      transformed Gaussian function offers the highest flexibility (best fits) to all
      shapes of chromatographic peaks, including extremely asymmetric tailing peaks
      with a peak asymmetry of up to 8. The flexibility of this function should improve
      our ability to process chromatographic peaks such as deconvolution of overlapped
      peaks and smoothing noisy peaks for the determination of statistical moments.

PMID- 12064547
TI  - Utilization of synergetic effect of weak interactions in the design of polymeric
      sorbents with high sorption selectivity.
AB  - Cystine and tyrosine were used as model sorbates to illustrate the design of
      sorbents with high sorption selectivity using two types of weak interactions that
      act synergistically. When two types of weak interactions are the driving forces
      in a sorption and they act synergistically, the second interaction would be
      effectively intramolecular. The entropy lost for the second interaction should be
      lower than that for the same interaction that occurs alone, and thus a
      significant enhancement of sorption should result. We designed an N-acetyl
      aminomethyl polystyrene resin (N-acetyl HC-D309), which was expected to sorb
      tyrosine through hydrophobic interaction and hydrogen bonding but not cystine.
      The chromatographic results for tyrosine and cystine indicate that the separation
      efficiencies on the N-acetyl HC-D309 column are higher than those on a styrene
      divinylbenzene copolymer column, on which sorption should be driven by
      hydrophobic interaction only, and on an acrylamide-N,N'-methylene bisacrylamide
      copolymer column, on which sorption should be driven by hydrogen bonding only.
      Tyrosine as well as cystine had no retention at all on the acrylamide-N,N'
      methylene bisacrylamide copolymer column. indicating the hydrogen bonding had
      little contribution to the sorption when it acted alone. The above results
      further indicate that hydrophobic interaction and hydrogen bonding contributed to
      the sorption of tyrosine on N-acetyl HC-D309 and they also acted synergistically.
      One of the conclusions of this paper is that some weak interactions which
      contribute little to the sorption when they act alone may contribute to the
      sorption when they act synergistically with other interactions.

PMID- 12064548
TI  - Evaluation of n-valeraldehyde modified chitosan as a matrix for hydrophobic
      interaction chromatography.
AB  - The n-valeraldehyde modified Chitosan (pentyl-Chitosan CL) was prepared by Schiff
      base formation and hydrogenation. By studying the IR spectra of Chitosan and
      pentyl-Chitosan CL, it is suggested that a pentyl group is linked to 2'-NH, by a
      C-N bond. The influence of temperature and ionic strength on the adsorption of
      protein on pentyl-Chitosan CL were studied, and it was found that the behavior of
      adsorption met with the theory of hydrophobic interaction. The storage stability
      of these packing materials was also investigated, the results show storage in 20%
      ethanol at 4 degrees C is the most suitable condition. Alpha-amylase was purified
      successfully by hydrophobic interaction chromatography, using pentyl-Chitosan CL
      as hydrophobic matrix. The purification factor is about 2.5 and the recovery is
      over 82%.

PMID- 12064549
TI  - Effect of salt gradients on the separation of dilute mixtures of proteins by ion
      exchange in simulated moving beds.
AB  - Salt gradients can improve the efficiency during fractionation of proteins by ion
      exchange in simulated moving beds (SMBs). The gradients are formed using feed and
      desorbent solutions of different salt concentrations. The thus introduced regions
      of high and low affinity may reduce eluent consumption and resin inventory
      compared to isocratic SMB systems. This paper describes a procedure for the
      selection of the flow-rate ratios that enables successful fractionation of a
      dilute binary mixture of proteins in a salt gradient. The procedure is based on
      the so-called "triangle theory" and can be used both for upward gradients (where
      salt is predominantly transported by the liquid) and downward gradients (where
      salt is predominantly transported by the sorbent). The procedure is verified by
      experiments.

PMID- 12064550
TI  - Initial purification of recombinant botulinum neurotoxin fragments for
      pharmaceutical production using hydrophobic charge induction chromatography.
AB  - Initial purification of two serotypic variants of recombinant botulinum
      neurotoxin toxin heavy chain fragment [rBoNT(Hc)], produced intracellularly in
      the yeast Pichia pastoris, using hydrophobic charge induction chromatography
      (HCIC) is reported. HCIC employs a matrix containing a weakly ionizable ligand
      that binds proteins through hydrophobic interactions at neutral pH and elutes the
      proteins by charge repulsion at acidic pH. HCIC optimization led to different
      purification conditions for each of the proteins even though they have 58%
      sequence similarity. The HCIC resin has a higher affinity for the fragment of
      serotype A than that of serotype B. The 10% dynamic breakthrough capacity for the
      serotype A fragment is >12.5 mg per ml of resin and is approximately 3.5 mg or
      the serotype B fragment per ml of resin. Stable elution conditions are also
      different for the two serotypes. The serotype A fragment is unstable when citrate
      is used to elute the product. However the serotype B fragment is stable when
      eluted with citrate buffer, and it is further purified by a overnight
      precipitation caused by the citrate buffer. This paper reports the development
      strategy, dynamic capacity breakthrough curves, resin and separation
      reproducibility, and preliminary scale-up data. The summation of the data
      demonstrates that HCIC is a scaleable process step for biopharmaceutical
      production of rBoNT(Hc) proteins.

PMID- 12064551
TI  - Work-related reproductive, musculoskeletal and mental disorders among working
      women--history, current issues and future research directions.
AB  - According to the recent changes of working environments and socio-economical
      conditions, the proportion of working women are increasing in Japan.
      Characteristics of occupational workload and stress of Japanese working women are
      consistent with those in many industrialized countries except man-dominant
      culture. In this review we describe the history, current issues, and future
      research directions on occupational health of working women, especially focused
      on reproductive health, work-related musculo-skeletal disorders (WMSDs), and
      mental disorders. In the reproductive health survey, traditionally main concern
      was about pregnancy outcomes, then fecundity studies, such as time to pregnancy,
      became topics recently. Future research will be shifted to outcomes not only
      during pregnancy but also disorders of hormonal balance and climacterium or
      health conditions after menopause. WMSDs are reviewed on mainly gender difference
      and its causative factors. Historically, mental health of working women in Japan
      has focused on the job stress of nurses. We compare results with a lot of recent
      researches in Europe and U.S.A., where interaction between occupational stress
      and family roles were studied. It is not easy to predict the prospective status
      of female workers in Japan, but social, workplace and familial supports will
      enhance their health promotion.

PMID- 12064552
TI  - Gene expression assay for hazard assessment of chemicals.
AB  - Recent progress in our knowledge of gene expression systems provides evidence
      that many industrial chemicals affect the transcriptional machineries directly or
      indirectly, and gene expression is now recognized as one of the main targets of
      many chemicals. In view of the increasing number of man-made chemicals, it is
      therefore necessary to establish a reliable gene expression assay with rapidity
      and high sensitivity. Among various gene expression assays, the so-called
      reporter assay is now accepted as a suitable tool to assess hazardous effects of
      chemicals on gene expression. This article focuses on the principle and
      applications of the reporter assay in research on endocrine disrupters.

PMID- 12064553
TI  - Work improvement and occupational safety and health management systems: common
      features and research needs.
AB  - There is a growing trend in re-orientating occupational health research towards
      risk management. Such a trend is accelerated by the increasing attention to
      occupational safety and health management systems. The trend, also seen in many
      Asian countries, is offering new opportunities for strengthening primary
      prevention. Useful examples are provided from recent work improvement projects
      dealing with technology transfer, small workplaces and rural areas. Common
      features of both these work improvement projects and accepted occupational risk
      management principles are reviewed based on recent experiences in Asian
      countries. Such features seem highly relevant in examining the occupational
      health research strategies. These experiences clearly show that locally adjusted
      procedures for risk assessment and control must be developed. There are new
      research needs concerning (a) the effective ways to encourage voluntary control
      at the workplace; (b) practical methods for local risk assessment; and (c) the
      types of participatory steps leading to continual improvements in the varying
      local context. Criteria of action-oriented research that can contribute to more
      effective risk control in different settings are discussed. Six relevant criteria
      may be mentioned: (a) adaptive risk management; (b) work/risk relationships; (c)
      action-oriented risk assessment; (d) use of collective expertise; (e)
      participation of local people; and (f) mutual learning. It appears crucial to
      stimulate research into the practical risk control procedures adjusted to the
      local situation.

PMID- 12064554
TI  - An ergonomic questionnaire survey on the use of computers in schools.
AB  - A questionnaire was sent out to elementary, junior high and high schools in
      Yokohama and Kawasaki Cities from January to March 1998 regarding the use of
      personal computers by pupils and students. The survey included the questions that
      asked how often and in what environment computers are used, whether any
      instructions are given as to their use, children's working posture, and the
      effect on health. The results show that most schools are slow to develop
      instructive programs from the environmental or ergonomic point of view. So far
      there are not many children who complain of any serious symptoms such as pain in
      the neck, head or shoulders, but a future increase in the number of classes which
      involve computing, as well as the widespread popularity of home computers, will
      surely arouse a legitimate concern about the health of pupils and students, since
      they will spend more and more time operating the devices. An effective way to
      anticipate the problem is to provide young students with adequate knowledge of
      easy-on-body usage and environmental design, and now there is an urgent need for
      specific guidelines to protect them.

PMID- 12064555
TI  - Association of low job control with a decrease in memory (CD4+ CD45RO+) T
      lymphocytes in Japanese middle-aged male workers in an electric power plant.
AB  - To clarify the relationship between perceived job stress and lymphocyte
      subpopulations, a cross-sectional study was conducted in 231 male electric power
      plant workers (aged 40 to 60, mean 46 years). Job stress, i.e., job control, job
      demands, and social support at work, was assessed by means of the Japanese
      version of the Job Content Questionnaire. Blood samples were taken from all the
      workers, and numbers of CD4+ T lymphocyte subpopulations, total CD4+ T, T (CD3+)
      lymphocytes, CD16CD56+ natural killer (NK) cells, total lymphocytes, and white
      blood cells were determined. After controlling for age, number of cigarettes
      smoked per day, alcohol drinking, frequency of regular exercise, job demands, and
      social support at work by the partial correlation coefficients, numbers of memory
      (CD4+ CD45RO+) T, total CD4+ T, and total T (CD3+) lymphocytes were positively
      correlated with job control (p<0.05). Neither job demands nor social support at
      work showed significant correlations with lymphocyte subpopulations. It is
      suggested that lower job control is associated with a decrease in the number of
      CD4+ CD45RO+ T lymphocytes in male middle-aged workers.

PMID- 12064556
TI  - Associations of length of employment and working conditions with neck, shoulder
      and arm pain among nursery school teachers.
AB  - A cross-sectional questionnaire study was carried out on nursery school (NS)
      teachers in public nursery schools in N city in Japan to determine the magnitude
      of associations of probable risk factors with neck, shoulder, and arm pain,
      adjusting for potential confounders in logistic regression models. Of 1438
      subjects, responded to the questionnaire, 959 NS teachers in charge of a separate
      or mixed group of children were subjected to analyses. Prevalence of neck and/or
      shoulder pain was 33.6%-35.4% in NS teachers in charge of children aged 0, 0-1,
      4, and 5 in contrast to 25.0-29.8% in those in charge of children aged 1,2, and
      3. The prevalence of neck/shoulder pain tended to increase with the length of
      employment in all groups classified according to the age of children under care.
      In a logistic regression model that simultaneously adjusted demographic and
      personal variables, length of employment and care for children aged 0 in the
      workplace were found significantly associated with musculoskeletal pain. In
      further logistic models, pain in the neck/shoulders and arms had associations
      with some specific variables: care for children aged 0, holding/lifting a
      child/material, overwork, and poorly supported job situations. The odds ratios
      for those variables varied from 1.37 to 2.41. This results suggest that pain in
      the neck/shoulders and arms is induced by a wide variety of risk factors in NS
      teachers that include high physical workload, long working hours, job demand
      support imbalance, and cumulative influence of workloads.

PMID- 12064557
TI  - DNA microarray analysis of human gene expression induced by a non-lethal dose of
      cadmium.
AB  - Cadmium (Cd) is a hazardous heavy metal present in working and living
      environments. Cd affects many cellular functions, but little is known about the
      mechanisms of its toxicity and cellular defense against it. Recently, advanced
      gene expression analysis employing DNA microarrays provided us the means to
      profile the expression of thousands of genes simultaneously. We describe here a
      study of Cd-induced gene expression profile. Messenger RNA was prepared from HeLa
      cells exposed to a non-lethal dose of CdSO4, and analyzed by the use of an array
      consisting of 7,075 human cDNAs. Many stress response genes including those
      coding for metallothioneins and heat shock proteins were observed to be induced
      by Cd. The cellular metabolism inclined toward the synthesis of cysteine and
      glutathione after Cd exposure. Anti-oxidant genes also appeared to be induced to
      protect cell components and to quench reactive oxygen species. Ubiquitin pathway
      was activated as well probably to degrade proteins which might not be renatured.
      These data suggest that human cells mobilize every genomic resource (induction of
      some genes and repression of others) to overcome cytotoxicity caused by Cd.

PMID- 12064558
TI  - The introduction of an occupational health management system for solving issues
      in occupational health activities in Japan.
AB  - An important challenge to occupational health services in Japan is the necessary
      shift from regulation-based occupational health program to health risk-based
      program. The Occupational Safety and Health Management System (OSHMS) is an
      effective tool for introducing risk-based activities. To date, the Five
      Management system has been used to manage occupational health activities. This
      classification, however, does not show the interactions among the listed
      activities. Nor is it clear how this system contributes to the PDCA
      (Plan/Do/Check/Act) cycle for continual improvement. The category in the Five
      Management system called "Roles of the Occupational Physician" covers most of the
      occupational health services required in Japan. The items listed in the Five
      Management system were compared to the guidelines of OSHMS from the International
      Labour Office and issues that should be solved for occupational health activities
      with OSHMS were clarified. Seven issues are discussed in this paper; (1)
      occupational safety and health policy and audit that can drive the PDCA cycle
      effectively, (2) reclassification of occupational health activities with several
      different objectives, (3) set up of targets, (4) risk assessment methods that can
      prioritize health risks compared to safety risks, (5) exposure assessment methods
      for risk assessment, (6) flexibility of laws and regulations, and (7) development
      of talented professionals for risk-based occupational health activities.

PMID- 12064559
TI  - Assessment of the mutations of p53 suppressor gene and Ha- and Ki-ras oncogenes
      in malignant mesothelioma in relation to asbestos exposure: a study of 12
      American patients.
AB  - In our previous study, we found no genetic alteration in exons 1 and 2 of Ha- and
      Ki-ras oncogenes nor in exons 5 to 9 of the p53 suppressor gene in seven Japanese
      malignant mesothelioma patients exposed to asbestos. To examine further whether
      malignant mesothelioma due to asbestos has genetic alterations in the p53
      suppressor gene and in Ha- and Ki-ras oncogenes, we analyzed point mutations of
      these genes in paraffin embedded operative open biopsied samples of the primary
      tumor of malignant mesothelioma in twelve American patients. The genetic analysis
      was conducted by the PCR-SSCP (polymerase chain reaction single-strand
      conformation polymorphism) method in all patients and by sequencing analysis of
      DNA bases in the two patients with suspected gene mutation. The analysis of the
      p53 suppressor gene showed an amino acid converting mutation of exon 7 in one
      patient and a polymorphism of exon 6 in another patient; the former patient was a
      heavy smoker with a biphasic cell type. No genetic alteration was found in exons
      1 and 2 of Ha- and Ki-ras oncogenes in any of the patients. The results suggest
      that the effects of asbestos on the p53 suppressor gene and Ha- and Ki-ras
      oncogenes in malignant mesothelioma are negligible. Further studies are needed to
      examine whether the observed mutation of the p53 suppressor gene is due to the
      combined effects of asbestos and smoking or to other unknown factors.

PMID- 12064560
TI  - Effects of safety behaviours with pesticide use on occurrence of acute symptoms
      in male and female tobacco-growing Malaysian farmers.
AB  - The effects of safety behaviours associated with pesticide use on the occurrence
      of acute organ symptoms in 395 male and 101 female tobacco-growing farmers in
      Malaysia were studied. We used a 15-questionnaire checklist on safe pesticide-use
      behaviours and a 25-questionnaire checklist on acute organ symptoms reported
      shortly after spraying pesticides. Results of stepwise multiple linear regression
      analysis indicated that no smoking while spraying, good sprayer-condition, and
      changing clothes immediately after spraying significantly prevented occurrence of
      acute symptoms just after pesticide spray in male farmers; in female farmers,
      only wearing a hat while spraying significantly prevented the symptoms. Safety
      behaviours in pesticide use in male and female tobacco-growing farmers are
      discussed in the light of these findings.

PMID- 12064561
TI  - Anti-implantation effect of a carbamate fungicide mancozeb in albino mice.
AB  - Mancozeb, an organocarbamate fungicide, was administered to examine the effect on
      implantation at doses of 18, 24, 30 and 36 mg/kg body weight/d to normal virgin
      swiss albino mice for 8 days to pregnant mice. The vaginal smear and body weight
      of the mice were recorded daily and mice were sacrificed on 9th day of pregnancy.
      There was a complete inhibition of implantation in 36 mg mancozeb treated mice
      with 100% pre-implantation loss. There was a partial inhibition of implantation
      in 24 and 30 mg mancozeb treated mice with 53.44 and 90.16% pre-implantation loss
      respectively. However, implantation was not affected in 18 mg mancozeb treated
      mice with 4.92% pre-implantation loss when compared to oil treated controls. To
      study the temporal effect, the effective dose of 36 mg/kg body weight/d mancozeb
      was administered orally for 3 and 5 days and on day 3 only. There was a complete
      inhibition of implantation in 5 days treated mice with 100% pre-implantation loss
      and partial inhibition of implantation of 3 days treated mice with 75% pre
      implantation loss. However, implantation was not affected in mice treated on day
      3 only with 1.63% pre-implantation loss when compared to control mice. There was
      a significant decrease in the diestrus phase with the result there was a
      concomitant increase in the estrus phase and there was a significant decrease in
      the uterus weight with 24, 30 and 36 mg and for 3 and 5 days with 36 mg mancozeb
      treatment. Inhibition of implantation by mancozeb may be due to hormonal
      imbalance or its toxic effects.

PMID- 12064562
TI  - Effects of a standing aid on loads on low back and legs during dishwashing.
AB  - In order to prevent low back pain during dishwashing, we developed a standing aid
      for supporting the forward bending posture, and then evaluated the effects of the
      standing aid on decreasing load on the low back and legs. Eight female volunteers
      were asked to wash plates for 60 minutes in each of three working postures: (a)
      without the standing aid, (b) with the standing aid under the thighs, and (c)
      with the standing aid under the shins. The following were measured:
      electromyogram (EMG), electrocardiogram (ECG), the force applied to the standing
      aid, the ground reaction force, the bending angle of the trunk, the bending angle
      of the knee, and local discomfort in body regions. While using the standing aid
      under the shins, the muscle load decreased in the low back and legs. While using
      the standing aid under the thighs, the muscle loads decreased in the low back but
      increased in the legs. It was suggested that the standing aid under the shins was
      more effective in decreasing the load on the low back and legs than the standing
      aid under the thighs.

PMID- 12064563
TI  - Possible adverse effect of chromium in occupational exposure of tannery workers.
AB  - Our aim was to investigate the adverse effects of occupational exposure to
      trivalent chromium. We measured chromium and iron levels in serum and urine and
      hemoglobin levels in tannery workers and unexposed persons. We studied three
      groups of subjects. Group 1 included 15 non-smoking male tannery workers highly
      exposed to chromium from tanning and retanning departments. Group 2 included 14
      non-smoking male tannery workers with moderate chromium exposure from dying,
      drying and finishing departments. Group 3 included 11 healthy, non-smoking male
      subjects without direct chromium exposure. Higher serum chromium levels were
      observed in groups 1 and 2 with respect to group 3 (mean values respectively:
      0.43; 0.25 and 0.13 microg x l(-1)). Urine chromium levels in group 1 were higher
      than those in controls (mean values: 1.78 and 1.35 microg x l(-1)). In group 1 an
      inverse association was found between serum chromium and urine iron (-0.524),
      urine chromium and hemoglobin (-0.594) and between the urine chromium to iron
      ratio and hemoglobin (-0.693, p<0.05). The results suggest a chromium adverse
      effect on iron metabolism, possibly associated with excessive body chromium
      accumulation. In conclusion, chromium urine test could be recommended for
      diagnosis of chromium adverse effect on iron metabolism. Further studies are
      needed to quantify the relationship between urine chromium and hemoglobin
      metabolism.

PMID- 12064565
TI  - International trends in occupational health research and practice.
AB  - The paper argues for a "new generation" approach to occupational health, laying
      foundations for future demands. Occupational health deals with issues which are
      at the heart of the economy and society, and are beginning to attract increasing
      attention of politicians. Old disciplinary barriers must be crossed, and
      communication improved so that healthy work is accepted as a mainstream concern.
      This presents challenges both to occupational health professionals and to those
      with responsibilities for policy. As a first step, we need to make more effective
      use of the body of available research, and develop an understanding of how the
      conclusions from research can inform responsible decision making.

PMID- 12064564
TI  - Negative effect of photocopier toner on alveolar macrophages determined by in
      vitro magnetometric evaluation.
AB  - Photocopier toner has been implicated in the etiology of some pulmonary diseases.
      We examined here the in vitro toxicity of toner particles to alveolar
      macrophages. Cell magnetometry revealed that relaxation was not delayed in
      macrophages exposed to toner, which represents a rapid decrease in the remaining
      magnetism emitted by phagocytosed magnetite. However, relaxation was delayed in
      macrophages exposed to silica (positive controls). The release of intracellular
      LDH enzyme activity to the extracellular space was negligible in cells exposed to
      toner compared with negative and positive controls. Morphological examinations by
      light and electron microscopy revealed no abnormal findings in the exposed cells.
      A histochemical study using TUNEL staining and the electrophoretic profile of DNA
      obtained from cells exposed to toner and to silica were negative for apoptosis.
      The results of the present and other investigations into animal exposure indicate
      that photocopier toner is toxicologically inert. However, although the present
      study examined only effects in vitro, exposure to toner should be minimized
      because lung overloading in animals has been reported.

PMID- 12064566
TI  - Trends of research and practice in "occupational risk prevention" as seen in
      Germany.
AB  - Hypothesis and scenarios of future developments in ORP and ORP research are
      derived. Based on an analysis of events in the past, on the content and process
      of research projects in the German "humanization" program, on literature analysis
      and expert interviews 19 anamnesis to diagnosis relationships are formulated
      concentrating on the following topics: 1. Innovation potentials and value systems
      of ORP research, 2. Fields and topics of ORP research of the future, 3. Service
      oriented systems of actors in ORP, 4. Demands and limits for research transfer.
      So the creative potential of the ORP community in Germany was used to conclude on
      recommendations for ORP developments.

PMID- 12064567
TI  - Clinical pharmacology of bivalirudin.
AB  - Much progress has been made in understanding and treating acute coronary
      syndromes. For patients undergoing percutaneous transluminal coronary
      angioplasty, anticoagulant therapy during the procedure must strike a balance
      between providing sufficient anticoagulation to prevent thrombus formation and
      ischemic complications while averting hemorrhagic complications. Bivalirudin, a
      thrombin-specific anticoagulant, is the only anticoagulant that reduces both
      ischemic and bleeding complications associated with percutaneous coronary
      intervention (PCI). Bivalirudin is easy to use, provides predictable
      anticoagulation, inactivates both free and clot-bound thrombin, and blocks
      thrombin-mediated platelet activation and aggregation. Drug-drug interaction
      studies have found no clinically relevant interactions between bivalirudin and
      ticlopidine, abciximab, tirofiban, or eptifibatide. Bivalirudin is well tolerated
      by patients who previously received low-molecular-weight heparin (LMWH), when
      LMWH is discontinued 8-14 hours before bivalirudin is started. Similarly,
      switching from heparin to bivalirudin at the time of PCI reduces both ischemic
      and bleeding events.

PMID- 12064568
TI  - Bivalirudin administration during percutaneous coronary intervention: emphasis on
      high-risk patients.
AB  - In a large phase III study of patients with unstable angina treated with
      percutaneous transluminal coronary angioplasty (PTCA), the thrombin-specific
      anticoagulant bivalirudin produced relative risk reductions of 22% (p = 0.039)
      for ischemic complications and 62% (p < 0.001) for bleeding complications
      compared with heparin. Subsequent reports have shown that between-treatment
      differences favoring fewer complications with bivalirudin also extend to high
      risk patients. Early heparinization promotes heparin resistance and decreases
      activated clotting time achieved during PTCA. These effects are relevant to
      patients with postinfarction angina, which is associated with a greater
      likelihood of early vessel closure and procedural failure. In 1006 patients with
      one or both of these risk factors, bivalirudin significantly reduced combined
      ischemic and bleeding complications compared with heparin (8.6% vs 18%, p <
      0.001). Treatment separations favoring bivalirudin increased with risk,
      suggesting decreased heparin effectiveness in patients at heightened risk.
      Findings in three additional risk groups-women, the elderly, and patients not
      receiving glycoprotein IIb/IIIa inhibitors-also showed fewer complications with
      bivalirudin therapy. Preliminary data suggest that bivalirudin can be combined
      safely with glycoprotein IIb/Illa antagonists in percutaneous coronary
      intervention (PCI), including PTCA. An ongoing trial is aimed at determining the
      efficacy and safety of heparin with planned glycoprotein IIb/IIIa therapy versus
      bivalirudin with provisional glycoprotein IIb/IIIa therapy. The use of
      bivalirudin in patients with heparin-induced thrombocytopenia also is being
      evaluated after favorable findings in early compassionate-use studies. The fact
      that between-treatment differences favoring bivalirudin were especially
      outstanding among the high-risk patients considered in this review reinforces the
      impression that bivalirudin is a promising and unprecedented alternative to
      heparin in PCI.

PMID- 12064569
TI  - A practical cost analysis of bivalirudin.
AB  - Despite advances in percutaneous coronary intervention (PCI) techniques and
      adjunctive therapies, the risks of ischemic and bleeding complications with PCI
      remain significant. These complications are associated with significant morbidity
      and mortality, as well as substantially higher costs. Bivalirudin is the only
      antithrombotic agent that has been shown to reduce both ischemic and hemorrhagic
      complications associated with PCI. Cost models drawn from the results of three
      clinical trials of bivalirudin have estimated its potential impact on total
      medical costs. In addition, the number needed to treat to avoid a bleeding
      complication has been calculated based on patients shown to have a heightened
      risk of bleeding in the Bivalirudin Angioplasty Trial. In all models assessed,
      the use of bivalirudin offset most of its own cost through reductions in bleeding
      and ischemic complications.

PMID- 12064570
TI  - The biology of thrombin in acute coronary syndromes.
AB  - Thrombin, a serine protease, is the keystone of the twin processes of hemostasis
      and thrombosis. Through procoagulant, anticoagulant, and antifibrinolytic
      mechanisms, thrombin helps maintain vascular integrity in the face of hemorrhage.
      These same mechanisms, however, allow for the pathologic formation of thrombi in
      response to endothelial damage, which accompanies the erosion or rupture of
      atherosclerotic plaques. Alone or incorporated into plaques, thrombi can cause
      vessel occlusion resulting in acute coronary syndromes (ACS). Inhibiting thrombin
      can improve clinical outcomes in ACS, as well as in procedures such as
      percutaneous coronary interventions, which are designed to open the occluded
      vessels that cause ACS. Such improvements in outcomes with thrombin inhibition
      reflect the central and multivariate role of thrombin in thrombus formation.

PMID- 12064571
TI  - The role of thrombin inhibition during percutaneous coronary intervention.
AB  - Acute coronary syndromes encompass a spectrum of conditions, including myocardial
      infarction and unstable angina. These syndromes are related to the formation and
      disruption of atherosclerotic plaque. Rupture of plaque leads to thrombin
      generation, fibrin deposition, and platelet aggregation, ultimately resulting in
      restriction of blood flow and ischemia of cardiac tissue. Percutaneous coronary
      intervention (PCI), including angioplasty and coronary stent placement, has been
      developed to open occluded arteries. The frequency with which these procedures
      are performed speaks to their largely successful outcomes. However, the
      mechanical manipulations of PCI result in additional plaque rupture and damage to
      the vessel wall, exposing subendothelial components to blood and resulting in the
      initiation of the clotting cascade and in platelet activation. Left unchecked,
      these intertwined processes lead to formation of arterial thrombi at the site of
      endothelial damage, and potentially to abrupt vessel closure or embolization of
      thrombi into the distal microcirculation. Thrombin plays a central role in
      thrombus formation and platelet activation, and its inhibition significantly
      reduces thrombus-related sequelae. Current antithrombotic strategies during PCI
      are based on the traditional indirect thrombin inhibitor heparin. Heparin has
      several limitations in efficacy and safety, due in part to its indirect mechanism
      of action. Bivalirudin, a direct thrombin inhibitor, offers significant
      improvement over heparin in the clinical outcomes and risks associated with PCI.

PMID- 12064572
TI  - Differential display: a critical analysis.
AB  - Differential display (DD) is a well-established analytical tool for measuring
      gene expression that is still popular due to its documented success and ability
      to identify novel genes not yet available for analysis by more powerful
      microarray hybridization. For a comprehensive analysis of all mRNAs in a given
      cell, it is statistically predicted that at least 240 different DD primer
      combinations are required. This prediction, however, has never been empirically
      tested. Using far more primer combinations than that predicted to evaluate 90% of
      the mRNAs in a cell, plus other modifications, we identified and confirmed the
      induction of five mRNAs by hydrogen peroxide in HA-1 hamster cells. However, five
      other known oxidant-inducible mRNAs were not identified by DD. Filter microarray
      hybridization did not result in the identification of any additional species
      modulated twofold or greater but previous two-dimensional protein gel
      electrophoresis identified 15 induced protein species. We conclude that the
      current statistical prediction for comprehensive analysis of all the mRNAs in a
      given cell is inaccurate, at least in our hands, and further conclude that DD is
      a useful but less than comprehensive method for assessing changes in mRNA levels.

PMID- 12064573
TI  - Genetic analysis of the basis of translation in the -1 frame of an unusual non
      ORF sequence isolated from phage display.
AB  - An unusual peptide-encoding sequence, called H10, and several derivatives of this
      sequence were previously isolated from a random peptide library screened by phage
      display during drug discovery protocols. The H10 family of sequences had the
      unusual property of being expressed despite the absence of an open reading frame.
      When these sequences were fused to a reporter lacZ gene in all three frames, beta
      galactosidase was expressed not only from the parental non-open reading frame,
      consistent with the original isolations, but also from the frame -1 to the
      parental. This unexpected translation in a second reading frame could result from
      either a recoding event or from an internal translation initiation event. In
      order to elucidate which type of event, a genetic approach was selected to
      eliminate a potential downstream initiator site within the H10 sequence. This
      report provides strong evidence that translation in the -1 frame in this family
      of sequences is indeed originating from a downstream translation initiation
      event. Unexpectedly, the mutation eliminating the downstream initiation event in
      the -1 frame simultaneously elevated expression in the original non-open reading
      frame.

PMID- 12064574
TI  - Heterogeneity in expression of DNA polymerase beta and DNA repair activity in
      human tumor cell lines.
AB  - The 39-kDa DNA polymerase beta (pol beta) is an essential enzyme in short-patch
      base excision repair pathway. A wild-type and a truncated forms of pol beta
      proteins are expressed in primary colorectal and breast adenocarcinomas and in a
      primary culture of renal cell carcinoma. To test whether pol beta has a
      contributory role in tumorigenicity of human tumor cell lines, we have undertaken
      a study to determine expression of pol beta in colon, breast, and prostate tumor
      cell lines. Unlike primary colon tumor cells, three types of pol beta mRNA have
      been identified in HCT116, LoVo, and DLD1, colon tumor cell lines. A 111-bp
      deleted pol beta transcript was expressed in MCF7, a breast tumor cell line, but
      not in primary breast tumor cells. An expression of a smaller pol beta transcript
      has been revealed in DU145, a prostate tumor cell line, whereas, a single base
      (T) deletion in mRNA at codon 191 was found in prostate cancer tissue.
      Interestingly, a wild-type pol beta transcript was also expressed in all tumor
      cell lines similar to primary tumor cells. Furthermore, the cell extract of LoVo
      exhibited highest gap-filling synthesis function of pol beta when the extract of
      DU145 showed lowest activity. MNNG, a DNA alkylating agent, enhanced the gap
      filling synthesis activity in extracts of LoVo cell line. Furthermore, the
      cellular viability of LoVo and HCT116 cells is sensitive to MNNG when DU145 cells
      are resistant. These results demonstrate heterogeneity in pol beta mRNA
      expression, which may be a risk factor related to tumorigenic activities of tumor
      cell lines.

PMID- 12064575
TI  - Modulation of c-myc, max, and mad gene expression during neural differentiation
      of embryonic stem cells by all-trans-retinoic acid.
AB  - c-Myc regulates cellular proliferation, differentiation, and apoptosis. Temporal
      expression of c-Myc during all-trans-retinoic acid (RA)-mediated neural
      differentiation in murine embryonic stem cell (ES) was investigated. Correlation
      to the modulation of dimerizing partners Max and Mad that may influence c-Myc
      signaling and transcription regulation was elucidated for the first time in these
      cells. In RA-treated cells, increase in c-myc mRNA was detected by reverse
      transcriptase polymerase chain reaction on days 11 and 14 of differentiation
      compared with the vehicle-treated controls. The results were further corroborated
      by ribonuclease protection assay (RPA). Western blots revealed an increase in c
      Myc protein only on day 14 of differentiation in RA-treated cells. Increases in
      max and mad gene transcription detected by RPA at times of elevated c-Myc in RA
      treated ES cells suggest that a transient increase in c-Myc protein expression
      may influence differential dimerization of Myc partners needed for signaling in
      the neural differentiation of ES cells.

PMID- 12064577
TI  - A festschrift in honor of Halsted R. Holman, MD: action research in health care.

PMID- 12064578
TI  - A conversation about the clinical scholars program: the training of nonbiomedical
      fellows inside the modern academic medical center. Interview by Joel R. Gardner,
      Julius Krevans, and Margaret Mahoney.
AB  - BACKGROUND: The Robert Wood Johnson Clinical Scholars Program is arguably the
      best example of "action research" in postgraduate medical education conducted in
      the second half of the twentieth century. Since its inception in the late 1960s,
      the program has sought to improve the sensitivity of medical care to its
      constituents by producing a new kind of physician-one with the skills to
      rigorously assess the societal forces that impact health care and effect useful
      change. METHODS: An oral history interview with Dr. Halsted Holman, one of the
      surviving founders, regarding his personal impressions of the program after 30
      years of operation. RESULTS: The greatest success of the program is its scholars.
      Today, nearly 1,000 alumni are ubiquitous in health care, from the hallowed ranks
      of the Institute of Medicine to departments of medicine, as heads of hospitals
      and leaders of government, from federal and state agencies to statehouses
      throughout the United States, and even to the Surgeon General's office. However,
      as a revolutionary departure in academics, the program has to watch out that in
      its maturation and senescence it does not miss opportunities to embrace new
      disciplines, new methods, and new focuses of investigation. CONCLUSION:
      Philanthropy can come together with courageous leadership to successfully
      challenge educational orthodoxy.

PMID- 12064576
TI  - Analysis of the mutations in the active site of the RNA-dependent RNA polymerase
      of human parainfluenza virus type 3 (HPIV3).
AB  - The large protein (L) of the human parainfluenza virus type 3 (HPIV3) is the
      functional RNA-dependent RNA polymerase, which possesses highly conserved
      residues QGDNQ located within motif C of domain III comprising the putative
      polymerase active site. We have characterized the role of the QGDNQ residues as
      well as the residues flanking this region in the polymerase activity of the L
      protein by site-directed mutagenesis and examining the polymerase activity of the
      wild-type and mutant L proteins by an in vivo minigenome replication assay and an
      in vitro mRNA transcription assay. All mutations in the QGDNQ residues abolished
      transcription while mutations in the flanking residues gave rise to variable
      polymerase activities. These observations support the contention that the QGDNQ
      sequence is absolutely required for the polymerase activity of the HPIV3 RNA
      dependent RNA polymerase.

PMID- 12064579
TI  - The Midpeninsula Health Service: action research using small primary care groups
      to provide evidence-based medicine that empowers patients while continuously
      improving quality and lowering costs.
AB  - OBJECTIVES: A Joint Planning Committee Report was issued in 1974 exploring how
      Stanford University might itself provide primary care to students, faculty,
      employees and their dependents at low cost. The report called for the creation of
      a health maintenance organization owned by its subscribers in affiliation with
      Stanford Medical Center. However, because the report was dismissed by the dean of
      the School of Medicine as being unworkable, the Midpeninsula Health Service (MHS)
      began operating as an unaffiliated, nonprofit health plan in downtown Palo Alto
      in January 1976. The MHS's planning, early operation, move to the Stanford
      campus, financial viability and ultimate fate are examined as an example of
      action research in health care. METHODS: Source documents were examined by the
      authors, a founding MHS board member and its two inaugural medical directors, in
      compiling a 30-year organizational history. RESULTS: The MHS was remarkably
      prescient in its early use of small primary care groups that included midlevel
      practitioners, the principles of evidence-based medicine, the participation of
      patients in self-care activities, and a commitment to the continuous monitoring
      and improvement of quality. Imputed annualized costs of care were 30% lower than
      contemporary fee-for-service care and 20% lower than that of Kaiser, with no
      discernible difference in health outcomes. CONCLUSION: Action research methods
      can be useful in identifying and testing potential solutions to vexing problems
      in health care delivery.

PMID- 12064580
TI  - Self-care and the doctor-patient relationship.
AB  - OBJECTIVES: An important factor contributing to the steep rise in health care
      costs in the late 1960s was a reversal from the predominance of acute illness to
      that of chronic disease. Beginning with the philosophy of Illich and Levin, and
      the practical instruments of Fries, Sehnert, Vickery, and Ferguson, a new
      movement in patient self-care emerged. However, such programs were not integrated
      into organized medical care plans and though theoretically attractive had not yet
      proven to improve health or decrease costs. METHODS: The contributions to the
      self-care movement made under the intellectual guidance of Halsted Holman and the
      relevant literature produced are reviewed. RESULTS: While caring for chronic
      rheumatic diseases, Halsted Holman discovered that patient self-report was a more
      powerful predictor of outcome than were traditional biologic measures such as
      anti-DNA antibodies. Realizing the role that patient knowledge of their own
      disease course might play, he developed the Arthritis Self-Management course, a
      lay-led self-care program emphasizing patient participation. Holman and
      colleagues next elucidated the pivotal importance of Bandura's theory of self
      efficacy in the improved patient outcomes initially observed. These self-care
      techniques were woven into the structure of the Midpeninsula Health Service,
      showing for the first time reductions in subsequent office visits and enhanced
      quality. In partnership with Kaiser Health Plan, these techniques showed
      improvements in self-efficacy health behaviors, status, and use in a randomized
      trial of more than 1,000 patients. CONCLUSION: Halsted Holman and colleagues have
      played a seminal role in the translation of academic self-care theory into
      community practice.

PMID- 12064581
TI  - Measuring clinically important changes with patient-oriented questionnaires.
AB  - BACKGROUND: The measurement of the patient's experience with a condition or an
      illness is an important and quantifiable outcome and an example of action
      research. By making these concerns paramount, the goals and processes of health
      care can be redirected from anatomical and physiologic restoration to patient
      oriented outcomes. At the same time, research can illuminate the complex
      mechanisms responsible. METHODS: Critical, analytic synthesis and review of the
      research evaluating the ability of self-administered questionnaires to capture
      clinically meaningful changes. RESULTS: Responsiveness is differentiated from
      sensitivity, and statistical methods for evaluating sensitivity of instruments
      are referenced. Techniques for evaluating whether differences in instrument
      sensitivity could have occurred by chance are presented, and methods for
      assessing a clinically meaningful change are discussed. CONCLUSION:
      Responsiveness is the key psychometric property of an instrument if it is to be
      incorporated into daily practice. Improving responsiveness is a major research
      priority.

PMID- 12064582
TI  - Connexin genes in the mouse and human genome.
AB  - Gap junctions serve for direct intercellular communication by docking of two
      hemichannels in adjacent cells thereby forming conduits between the cytoplasmic
      compartments of adjacent cells. Connexin genes code for subunit proteins of gap
      junction channels and are members of large gene families in mammals. So far, 17
      connexin (Cx) genes have been described and characterized in the murine genome.
      For most of them, orthologues in the human genome have been found (see White and
      Paul 1999; Manthey et al. 1999; Teubner et al. 2001; Sohl et al. 2001). We have
      recently performed searches for connexin genes in murine and human gene libraries
      available at EMBL/Heidelberg, NCBI and the Celera company that have increased the
      number of identified connexins to 19 in mouse and 20 in humans. For one mouse
      connexin gene and two human connexin genes we did not find orthologues in the
      other genome. Here we present a short overview on distinct connexin genes which
      we found in the mouse and human genome and which may include all members of this
      gene family, if no further connexin gene will be discovered in the remaining non
      sequenced parts (about 1-5%) of the genomes.

PMID- 12064583
TI  - Cloning and functional expression of a novel human connexin-25 gene.
AB  - Gap junctions are intercellular, water-filled channels composed of transmembrane
      proteins called connexins, six of which are arranged radially and dock with six
      homologous proteins in an adjacent cell to form an approximate 16 A pore. Through
      this pore cell-to-cell transfer of small water-soluble molecules up to about 1000
      daltons occurs along concentration gradients. Connexins comprise a multigene
      family that share consensus sequences in the trans-membrane domains and the first
      and second extracellular loops. Comparison of the protein sequences of known
      human connexins with the draft nucleotide sequence of the human genome revealed
      two clones from chromosome 6 which showed strong similarity to highly conserved
      connexin sequences. Detailed analysis revealed the presence of a 672 nt open
      reading frame in these clones, encoding a 223 amino acid polypeptide with a
      predicted molecular weight of about 25 kD. This is smaller than other known human
      connexins. The ORF of the potential connexin25 was amplified by semi-nested PCR
      using human genomic DNA as a template. To confirm that this new gene encodes a
      connexin, Cx25 was transfected into a gap junction deficient subclone of the
      human HeLa cell line. After selection of transformants, cells were microinjected
      with the fluorescent dye Lucifer yellow. Transfectants but not controls
      successfully transferred dye, demonstrating that this new gene encodes a
      functional connexin.

PMID- 12064584
TI  - Identification and functional expression of HCx31.9, a novel gap junction gene.
AB  - By combining in silico and bench molecular biology methods we have identified a
      novel human gap junction gene that encodes a protein designated HCx31.9. We have
      determined its human chromosomal location and gene structure, and we have
      identified a putative mouse ortholog, mCx30.2. We have observed the presence of
      HCx31.9 in human cerebral cortex, liver, heart, spleen, lung, and kidney and the
      presence of mCx30.2 in mouse cerebral cortex, liver and lung. Moreover,
      preliminary data on the electrophysiological properties of HCx31.9 have been
      obtained by functional expression in paired Xenopus oocytes and in transfected
      N2A cells.

PMID- 12064585
TI  - Application of SCAM (substituted cysteine accessibility method) to gap junction
      intercellular channels.
AB  - The pore-lining residues of gap junction channels determine their permeability to
      ions and small cellular metabolites. These residues can be identified through
      systematic cysteine substitution and accessibility analysis, commonly known as
      SCAM (Substituted Cysteine Accessibility Method). However, application of this
      technique to intercellular channels is more complicated than for their
      transmembrane counterparts. We have utilized a novel dual-oocyte perfusion device
      to apply cysteine reagents to the cytoplasmic face of paired, voltage-clamped
      Xenopus oocytes. In this configuration, a large and irreversible cysteine reagent
      MBB (maliemidobutyryl biocytin, mw 537) was shown to readily traverse the gap
      junction pore and induce conductance changes upon reaction of accessible sites.
      Of the 11 reactive sites identified, 6 were located in M3, where they span the
      bilayer. They display a periodicity characteristic of the tilted helix that lines
      the pore in the gap junction structure of Unger et al. (1999). Access to several
      of the other sites was attributed to aqueous crevices between transmembrane
      helices. Reactive sites were slightly different than those identified for gap
      junction hemichannels (Zhou et al. 1997), suggesting that conformational changes
      occur upon docking.

PMID- 12064586
TI  - Size selectivity between gap junction channels composed of different connexins.
AB  - Gap junction channels are traditionally viewed as large, nonspecific pores
      connecting cells. Recently the diversity in the connexin family has drawn more
      attention to their permeability characteristics. Several studies have shown that
      both size and charge contribute to the permeability of gap junctional channels.
      We have used a graded series of neutral polyethylene glycol probes (PEGs), which
      eliminate charge contribution completely, to specifically assess the physical
      exclusion limits of gap junction channels formed by different connexins. Cx 26,
      32 and 37 were expressed in paired Xenopus oocytes to form homotypic gap
      junctional channels. PEG probes were perfused intracellularly into one side of
      the oocyte pair. A reversible drop in conductance of the gap juctional channels
      indicated that the probe was small enough to enter the pore and hinder ion flux.
      Our data suggest that Cx32 channels have a size cut-off between PEG 400 (11.2 A)
      and PEG 300 (9.6 A) despite their relatively small single channel conductance
      (approximately 55 pS). Cx26 channels (approximately 130 pS single channel
      conductance) have a size exclusion limit around PEG 200 (8.0 A), while Cx37
      channels show the most restricted size cut-off between PEG 200 (8.0 A) and TriEG
      (6.8 A), despite having the largest unitary conductance (approximately 300 pS).

PMID- 12064587
TI  - Functional characteristics of heteromeric Cx40-Cx43 gap junction channel
      formation.
AB  - Cx40:Cx43 expression ratio in A7r5 cells is augmented in growth stimulated vs.
      growth arrested conditions. To determine the impact of changing Cx40:Cx43
      expression ratio on gap junction function, we have developed A7r5 cell lines that
      display Cx40:Cx43 ratios of 1:1 (66B5n) and 10:1 (A7r540C3). When Rin43 cells
      were paired with these coexpressing cells, there was an increasing asymmetry of
      voltage dependent gating as the Cx40:Cx43 ratio increased in the coexpressing
      cell. This asymmetry was opposite to that which is predicted by Cx40/Cx43
      heterotypic channels. In addition, when Rin43 cells were paired with coexpressing
      cells there was a shift toward smaller single channel event amplitudes with
      increasing Cx40:Cx43 ratio in the coexpressing cell. Again, this is opposite to
      that which is predicted by Cx40/Cx43 heterotypic channels. In dye coupling
      experiments, 6B5N, A7r5, and A7r540C3 cells displayed charge and size selectivity
      that increased with increasing Cx40:Cx43 expression ratio. These data indicate
      that although the electrophysiological properties of heteromeric/heterotypic
      channels are not directly related to the proportions of Cx constituents that
      comprise the channel, the dye permeability data fit what would be predicted by an
      increase in Cx40:Cx43 ratio.

PMID- 12064588
TI  - Heteromeric mixing of connexins: compatibility of partners and functional
      consequences.
AB  - Cx43 is widely expressed in many different cell types, and many of these cells
      also express other connexins. If these connexins are capable of mixing, the
      functional properties of channels containing heteromeric connexons may
      substantially influence intercellular communication between such cells. We used
      biochemical strategies (sedimentation through sucrose gradients, co
      immunoprecipitation, or co-purification by Ni-NTA chromatography) to examine
      heteromeric mixing of Cx43 with other connexins (including Cx26, Cx37, Cx40,
      Cx45, and Cx56) in transfected cells. These analyses showed that all of the
      tested connexins except Cx26 formed heteromeric connexons with Cx43. We used the
      double whole-cell patch-camp technique to analyze the electrophysiological
      properties of gap junction channels in pairs of co-expressing cells. Cx37 and
      Cx45 made a large variety of functional heteromeric combinations with Cx43 based
      on detection of many different single channel conductances. Most of the channel
      event sizes observed in cells co-expressing Cx40 and Cx43 were similar to those
      of homomeric Cx43 or Cx40 hemichannels in homo- or hetero-typic configurations.
      Our data suggest several different possible consequences of connexin co
      expression: (1) some combinations of connexins may form heteromeric connexons
      with novel proeprties; (2) some connexins may form heteromeric channels that do
      not have unique properties, and (3) some connexins may be incompatible for
      heteromeric mixing.

PMID- 12064589
TI  - Increased co-localization of connexin43 and ZO-1 in dissociated adult myocytes.
AB  - In the heart, the intercellular geometry of myocyte coupling by Connexin43-gap
      junctions (Cx43-gjs) is a determinant of normal and abnormal patterns of
      propagation of electrical excitation. ZO-1 has been suggested to play a role in
      determining the pattern of intercellular coupling between myocytes. We therefore
      investigated the co-distribution of Cx43 with ZO-1 in ventricular myocytes of the
      adult rat using quantitative immunoconfocal microscopy. Our data indicates that
      low-moderate levels of co-immunolocalization occur between Cx43 and ZO-1 in
      normal ventricular myocardium. However, rapid and significant increases in
      relative co-localization occur between Cx43 and ZO-1 following dissociation of
      myocytes from ventricular myocardium--a treatment inducing internalization of
      Cx43-gjs. This increased relative co-localization may represent an increase in
      Cx43-ZO-1 interaction, suggesting a role for ZO-1 in the remodeling of myocardial
      Cx43-gjs. A more comprehensive study, including immunoprecipitation and
      immunoelectron microscopy analyses has been carried out (Barker et al. Circ.
      Res., in press, 2002 and as presented to the 2001 International GJ Conference).
      This study further assesses the biological relevance of the increased association
      between ZO-1 and Cx43 accompanying internalization of Cx43-gjs.

PMID- 12064590
TI  - Connexin45 interacts with zonula occludens-1 in osteoblastic cells.
AB  - Connexin43 (Cx43) and Cx45 are co-expressed in a number of different tissues.
      Studies demonstrated that Cx45 transfected ROS (ROS/Cx45) cells, were less
      permeable to low molecular weight dyes than untransfected ROS cells, that have
      gap junctions made of Cx43. This suggests that there may be a functionally
      important interaction between Cx43 and Cx45 in these cells. One way in which
      these proteins may interact is by associating with the same set of proteins. In
      order to isolate connexin interacting proteins, we isolated Cx45 from Cx45
      transfected ROS cells (ROS/Cx45 cells) under mild detergent conditions. These
      studies showed that Cx45 co-purified with the tight junction protein, ZO-1.
      Immunofluorescence studies of ROS/Cx45 cells simultaneously stained with
      polyclonal Cx45 antibody and a monoclonal ZO-1 antibody showed that Cx45 and ZO-1
      colocalized in ROS/Cx45 cells. Furthermore we found that ZO-1 could bind to
      peptides derived from the carboxyl terminal of Cx45 that had been covalently
      bound to an agarose resin. These data suggests that Cx45 and ZO-1 directly
      interact in ROS/Cx45 cells.

PMID- 12064591
TI  - Characterization of the association of connexins and ZO-1 in the lens.
AB  - ZO-1 (Zona Occludens protein 1) has previously been shown to bind Cx43alpha1.
      This interaction involves the most C-terminal residues of Cx43alpha1 and the
      second PDZ-domain of ZO-1. The biological significance of this interaction is not
      well understood. The similarity of the C-terminal residues of the lens connexins
      Cx46alpha3 and Cx50alpha8 to Cx43alpha1 prompted us to examine if ZO-1 is
      expressed in the lens, and if ZO-1 interacts with lens connexins. A high level of
      ZO-1 expression was detected in the mouse lens. Lens connexins were shown to co
      immunoprecipitate with ZO-1, and the interaction was found to involve similar
      domains as those previously demonstrated for the Cx43alpha1/ZO-1 interaction
      (Nielsen et al. manuscript in preparation). Futhermore, transient expression of
      Cx46alpha3 and Cx50alpha8 in cell culture showed colocalization of gap junction
      plaques with ZO-1, further suggesting that lens connexins interact with ZO-1.
      Sequence comparison suggests that a large number of connexins of the alpha
      subclass may interact with ZO-1. Using the lens as a system to study connexin/ZO
      1 interactions may further our understanding of their biological significance in
      the lens, as well as in other organs.

PMID- 12064592
TI  - Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin.
AB  - Gap junctions are composed of connexins that form transmembrane channels between
      adjacent cells. The C-terminal tail of connexin-43 (Cx43), the most widely
      expressed connexin member, has been implicated in the regulation of Cx43 channel
      gating. Interestingly, channel-independent processes regulated by Cx43 have also
      been postulated. In our studies to elucidate the mechanism of Cx43 channel gating
      by growth factors and to explore additional functions of gap junctions, we have
      identified three interacting partners of the C-terminal tail of Cx43 (Cx43CT).
      (i) the c-Src tyrosine kinase, which phosphorylates Cx43CT and is involved in G
      protein-mediated inhibition of Cx43 gap junctional communication. (ii) the ZO-1
      'scaffold' protein, which might recruit signaling proteins into Cx43-based gap
      junctions. (iii) microtubules (consisting of alpha/beta-tubulin dimers), which
      extend with their distal ends to Cx43-based gap junctions, suggesting that Cx43
      gap junctions may play a novel role in regulating microtubule stability in
      contacted cells. Here we show that Cx43 binds alpha-tubulin equally well as beta
      tubulin. In addition, we show that the second, but not the first, PDZ domain of
      ZO-1 binds directly to Cx43, and we confirm that the very C-terminal isoleucine
      residue of Cx43 is critical for ZO-1 binding.

PMID- 12064593
TI  - Functional demonstration of connexin-protein binding using surface plasmon
      resonance.
AB  - Surface plasmon resonance (SPR) allows examination of protein-protein
      interactions in real time, from which both binding affinities and kinetics can be
      directly determined. We have used the SPR technique to search for proteins in
      heart tissue that would be candidate binding partners for the cardiac gap
      junction protein, connexin43 (Cx43). Heart lysate showed a strong, pH-dependent
      binding to the carboxyl terminus (CT) of Cx43 (amino acids 254-382) covalently
      linked to an SPR cuvette. Binding was inhibited by the presence of v-src
      transfected 3T3 cell lysate, suggesting that binding partners in these two
      lysates may compete for overlapping epitopes on Cx43CT. The combined application
      of proteomic and functional studies is expected to identify which proteins within
      heart tissue interact with Cx43 and what roles they may play in gap junction
      function.

PMID- 12064594
TI  - Role of cytoskeletal elements in the recruitment of Cx43-GFP and Cx26-YFP into
      gap junctions.
AB  - Cytoskeletal elements may be important in connexin transport to the cell surface,
      cell surface gap junction plaque formation and/or gap junction internalization.
      In this study, fluorescence recovery after photobleaching was used to examine the
      role of microfilaments and microtubules in the recruitment and coalescence of
      green fluorescent protein-tagged Cx43 (Cx43-GFP) or yellow fluorescent tagged
      Cx26 (Cx26-YFP) into gap junctions in NRK cells. In untreated cells, both Cx26
      YFP and Cx43-GFP were recruited into gap junctions within photobleached areas of
      cell-cell contact within 2 hrs. However, disruption of microfilaments with
      cytochalasin B inhibited the recruitment and assembly of both Cx26-YFP and Cx43
      GFP into gap junctions within photobleached areas. Surprisingly, disruption of
      microtubules with nocodazole inhibited the recruitment of Cx43-GFP into gap
      junctions but had limited effect on the transport and clustering of Cx26-YFP into
      gap junctions within the photobleached regions of cell-cell contact. These
      results suggest that the recruitment of Cx43-GFP and Cx26-YFP to the cell surface
      or their lateral clustering into gap junctions plaques is dependent in part on
      the presence of intact actin microfilaments while Cx43-GFP was more dependent on
      intact microtubules than Cx26-YFP.

PMID- 12064595
TI  - Distribution and dynamics of gap junction channels revealed in living cells.
AB  - To study the structural composition and dynamics of gap junctions in living
      cells, we tagged their subunit proteins, termed connexins, with the
      autofluorescent tracer green fluorescent protein (GFP) and its cyan (CFP) and
      yellow (YFP) color variants. Tagged connexins assembled normally and channels
      were functional. High-resolution fluorescence images of gap junction plaques
      assembled from CFP and YFP tagged connexins revealed that the mode of channel
      distribution is strictly dependent on the connexin isoforms. Co-distribution as
      well as segregation into well-separated domains was observed. Based on
      accompanying studies we propose that channel distribution is regulated by
      intrinsic, connexin isoform specific signals. High-resolution time-lapse images
      revealed that gap junctions, contrary to previous expectations, are dynamic
      assemblies of channels. Channels within clusters and clusters themselves are
      mobile and constantly undergo structural rearrangements. Movements are complex
      and allow channels to move, comparable to other plasma membrane proteins not
      anchored to cytoskeletal elements. Comprehensive analysis, however, demonstrated
      that gap junction channel movements are not driven by diffusion described to
      propel plasma membrane protein movement. Instead, recent studies suggest that
      movements of gap junction channels are indirect and predominantly propelled by
      plasma membrane lipid flow that results from metabolic endo- and exocytosis.

PMID- 12064596
TI  - Gap junction assembly: multiple connexin fluorophores identify complex
      trafficking pathways.
AB  - The assembly of gap junction channels was studied using mammalian cells
      expressing connexin (Cx) 26, 32 and 43 in which the carboxyl terminus was fused
      to green, yellow or cyan fluorescent proteins (GFP, YFP, CFP). Intracellular
      targeting of Cx32-CFP and 43-GFP to gap junctions was disrupted by brefeldin A
      treatment and resulted in a severe loss of gap junctional intercellular
      communication reflected by low intercellular dye transfer. Cells expressing Cx43
      GFP exposed to nocodazole showed normal targeting to gap junctions and dye
      transfer. Cx32 and 43 thus appear to be transported and assembled into gap
      junctions via the classical secretory pathway. In contrast, we found that
      assembly of Cx26-GFP into functional gap junctions was relatively unaffected by
      treatment of cells with brefeldin A, but was extremely sensitive to nocodazole
      treatment. Coexpression of Cx26-YFP and Cx32-CFP indicated a different
      intracellular distribution that was accentuated in the presence of brefeldin A,
      with the gap junctions in these cells constructed predominantly of Cx26-YFP. A
      site specific mutation in the first transmembrane domain that distinguished Cx32
      from Cx26 (Cx32128L) resulted in the adoption of the trafficking properties of
      Cx26 as well as its unusual post-translational membrane integration
      characteristics. The results indicate that multiple intracellular connexin
      trafficking routes exist and provide a further mechanism for regulating the
      connexin composition of gap junctions and thus specificity in intercellular
      signalling.

PMID- 12064597
TI  - Cx43/beta-gal inhibits Cx43 transport in the Golgi apparatus.
AB  - A connexin construct consisting of bacterial beta-galactosidase fused to the C
      terminus of connexin43 (Cx43/beta-gal) was used to examine Cx43 assembly in NIH
      3T3 cells. Cx43/beta-gal is retained in a perinuclear compartment and inhibits
      Cx43 transport to the cell surface. The intracellular connexin pool trapped by
      Cx43/beta-gal was retained in a compartment that co-localized with a medial Golgi
      apparatus marker by immunofluorescence microscopy and that was readily
      disassembled by treatment with brefeldin A. Further analysis by sucrose gradient
      fractionation showed that Cx43 and Cx43/beta-gal were assembled into a sub
      hexameric complex, and that Cx43/beta-gal expression also inhibited Cx43 assembly
      into hemichannels. While this is consistent with Cx43 hemichannel assembly in the
      trans Golgi network (TGN), these data also suggest that the dominant negative
      effect of Cx43/beta-gal on Cx43 trafficking may reflect a putative sub-hexameric
      assembly intermediate formed in the Golgi apparatus.

PMID- 12064598
TI  - Protein kinase C-epsilon mediates phorbol ester-induced phosphorylation of
      connexin-43.
AB  - We have used adenoviral vectors to express dominant negative variants of protein
      kinase C epsilon (PKCepsilon) or mitogen kinase kinase 1 (MKK1) to investigate
      their involvement in phorbol ester-induced connexin-43 (Cx43) phosphorylation in
      cardiomyocytes. Stimulation of cardiomyocytes with phorbol 12-myristate 13
      acetate (PMA) increased the fraction of the slower migrating (> or = 45 kDa) and
      more extensively phosphorylated Cx43 species. Expression of dominant negative
      MKK1 did not prevent the effect of PMA on Cx43 phosphorylation. Selective
      inhibition of PKCE significantly decreased baseline levels of Cx43
      phosphorylation and the PMA-induced accumulation of > or = 45 kDa Cx43. Thus,
      production of the more extensively phosphorylated species of Cx43 in
      cardiomyocytes by PMA requires activation of PKCepsilon.

PMID- 12064599
TI  - Protein kinase Calpha mediates the effect of antiarrhythmic peptide on gap
      junction conductance.
AB  - We investigated the effects of the antiarrhythmic peptide AAP10 (GAG-4Hyp-PY
      CONH2, 50 nM) on pairs of adult guinea pig cardiomyocytes and on pairs of HeLa
      cells transfected with rat connexin43 (Cx43). Using double cell voltage clamp
      technique in cardiomyocytes under control conditions, gap junction conductance
      (Gj) steadily decreased (by -0.3 to -0.4 nS/min). In contrast, 50 nM AAP10
      significantly enhanced Gj (by +0.22 to +0.29 nS/min). This effect of AAP10 could
      be significantly antagonized by bisindolylmaleimide I (BIM), and by the protein
      kinase C (PKC) subtype-specific inhibitors HBDDE (PKCgamma and -alpha) and CGP
      54345 (PKCalpha). In HeLa-Cx43 cells we found similar electrophysiological
      effects of AAP10. For further analysis, we incubated HeLa-Cx43 cells with
      [32P]orthophosphate (0.05 mCi/ml) for 4 h at 37 degrees C followed by addition of
      50 nM AAP10 for 15 min. We found that incorporation of 32P into Cx43 was
      significantly enhanced in the presence of AAP10, which was completely inhibited
      in presence of BIM. PKC enzyme-linked immunosorbent assay (ELISA) revealed
      significant activation of PKC by AAP10 in HeLa-Cx43 cells, which could be
      inhibited by HBDDE and CGP 54345. Finally, a binding study using [14C]-AAP10 as
      radioligand was performed. We found a saturable binding of [14C]-AAP10 with a KD
      of 0.88 nM to cardiac membrane preparations. For assessment of the antiarrhythmic
      activity in anesthetized rats, we infused aconitine until the occurrence of
      ventricular fibrillation (VF). The aconitine dose required for initiation of VF
      was significantly enhanced in the presence of AAP10. In conclusion; AAP10
      increases Gj in both adult cardiomyocytes and transfected HeLa-Cx43 cells. AAP10
      leads to enhanced phosphorylation of Cx43 via activation of PKCalpha. A membrane
      receptor exists for antiarrhythmic peptides.

PMID- 12064600
TI  - v-Src-mediated phosphorylation of connexin43 on tyrosine disrupts gap junctional
      communication in mammalian cells.
AB  - It is not clear how the v-Src oncoprotein disrupts gap junctional communication
      (GJC) established by connexin43 (Cx43) in mammalian cells. In this study, an
      experimental system was established to stably express v-Src and wild type (wt)
      Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout (KO) mouse
      cell line. When co-expressed with v-Src, the levels of phosphotyrosine (pTyr)
      from Y247F, Y265F, and Y247F/Y265F Cx43 mutants were reduced to approximately
      57%, 10%, and 2% of the level of pTyr from wt Cx43, indicating that Y247 and Y265
      were phosphorylation targets of v-Src in vivo. These data also implied that
      phosphorylation of Cx43 at Y265 was required for efficient phosphorylation of
      Cx43 at Y247. Most importantly, our measurements of GJC demonstrated that, in
      contrast to the wt Cx43 gap junction channels, the Y247F, Y265F, and Y247F/Y265F
      Cx43 channels were resistant to the disruption by v-Src. In conclusion, our
      studies support a model for processive phosphorylation of Cx43 on tyrosine, at
      the Y265 site followed by the Y247 site, in mediating the disruption of GJC
      induced by v-Src in mammalian cells.

PMID- 12064601
TI  - The regulatory role of the C-terminal domain of connexin43.
AB  - The C-terminal (CT) domain of connexin43 (Cx43) is thought to be important in the
      control of gap junction function via: a.) CT phosphorylation-dependent control of
      gap junction assembly and gating, b.) interactions of CT with key regulatory
      binding partners. To more closely examine CT-dependent regulation, we have
      expressed a hemagglutinin-Cx43CT (amino acids 235-382) fusion protein in Normal
      Rat Kidney (NRK) cells under a tetracycline-responsive inducible promoter.
      Western blot analysis shows that Cx43CT expression is markedly induced by at
      least 48 h oftreatment with the tetracycline analogue, doxycycline. Furthermore,
      Cx43CT is modified within the cell, as several treatments/conditions that
      increase endogenous Cx43 phosphorylation induced a mobility shift in Cx43CT.
      Treatment with kinase activators, including epidermal growth factor (EGF) and the
      tumor promoting phorbol ester 12-O-tetradecanylphorbol-13-acetate (TPA), caused a
      shift in the mobility of the Cx43CT in a manner consistent with the mobility
      shift observed upon increased phosphorylation of endogenous Cx43. Similarly,
      Cx43CT in mitotic cells is extensively shifted, consistent with reports which
      show that Cx43 is phosphorylated to a unique phosphoisoform in mitotic cells.
      These results indicate that the Cx43CT can interact with at least some of the
      kinases that phosphorylate endogenous Cx43 in cells and possibly modulate the
      effects of kinase activation on gap junctional communication.

PMID- 12064602
TI  - Calmodulin colocalizes with connexins and plays a direct role in gap junction
      channel gating.
AB  - The direct calmodulin (CaM) role in chemical gating was tested with CaM mutants,
      expressed in oocytes, and CaM-connexin labeling methods. CaMCC, a CaM mutant with
      greater Ca-sensitivity obtained by replacing the N-terminal EF hand pair with a
      duplication of the C-terminal pair, drastically increased the chemical gating
      sensitivity of Cx32 channels and decreased their Vj sensitivity. This only
      occurred when CaMCC was expressed before Cx32, suggesting that CaMCC, and by
      extension CaM, interacts with Cx32 before junction formation. Direct CaM-Cx
      interaction at junctional and cytoplasmic spots was demonstrated by confocal
      immunofluorescence microscopy in HeLa cells transfected with Cx32 and in
      cryosectioned mouse liver. This was confirmed in HeLa cells coexpressing Cx32-GFP
      (green) and CaM-RFP (red) or Cx32-CFP (cyan) and CaM-YFP (yellow) fusion
      proteins. Significantly, these cells did not form gap junctions. In contrast,
      HeLa cells expressing only one of the two fusion proteins (Cx32-GFP, Cx32-CFP,
      CaM-RFP or CaM-YFP) revealed both junctional and non-junctional fluorescent
      spots. In these cells, CaM-Cx32 colocalization was demonstrated by secondary
      immunofluorescent labeling of Cx32 in cells expressing CaM-YFP or CaM in cells
      expressing Cx32-GFP. CaM-Cx colocalization was further demonstrated at rat liver
      gap junctions by Freeze-fracture Replica Immunogold Labeling (FRIL).

PMID- 12064603
TI  - Mechanical stimulation of gap junctions in bone osteocytes is mediated by
      prostaglandin E2.
AB  - Gap junction-mediated intercellular communications are thought to transduce the
      effects of mechanical strain from osteocytes to cells on the bone surface to
      initiate remodeling. To determine whether gap junctions may co-ordinate the
      effects of mechanical loading, osteocyte-like MLO-Y4 cells were exposed to fluid
      flow-imposed shear stress. After exposure of MLO-Y4 to fluid flow, intercellular
      coupling increased in direct proportion to shear stress level. Interestingly,
      this stimulation is further enhanced during the post-stress period, indicating
      that released factor(s) is likely to be involved. The conditioned medium obtained
      from the fluid flow treated MLO-Y4 cells induced an increase in the number of
      functional gap junctions and Cx43 protein when added to non-sheer-stressed cells.
      Fluid flow was found to induce prostaglandin F2 (PGE2) release and increase
      cyclooxygenase 2 (COX-2) expression. When PGE2 was depleted from the fluid flow
      conditioned medium, the stimulatory effect on gap junctions was significantly
      decreased. Addition of the COX inhibitor indomethacin partially blocked the
      stimulatory effects of mechanical strain on gap junctions. Together, these
      studies suggest that the stimulatory effect of fluid flow on gap junctions is
      mediated in part by de novo synthesis and release of PGE2. Gap junctions may
      serve as channels for the signals generated by osteocytes in response to
      mechanical loading.

PMID- 12064604
TI  - Analysis of Cx43alpha1 promoter function in the developing zebrafish embryo.
AB  - The Cx43alpha1 gap junctions play an important role in cardiovascular
      development. Studies using transgenic mouse models have indicated that this
      involves an essential role for Cx43alpha1 in modulating neural crest cell
      motility. We previously showed that a 6.8 kb mouse genomic sequence containing
      the promoter and upstream regulatory sequences of the Cx43alpha1 gene can drive
      lacZ reporter gene expression in all neural crest cell lineages in the mouse
      embryo. To obtain further insights into the sequence motifs and regulatory
      pathways involved in targeting Cx43alpha1 gene expression in neural crest cells,
      we assayed the activity of the mouse Cx43alpha1 promoter in evolutionarily
      distantly related zebrafish embryos. For these studies, the 6.8kb Cx43alpha1
      genomic sequence and various deletion derivatives were used to generate GFP or
      lacZ expression vectors. The transcriptional activities of these constructs were
      analyzed in vivo after microinjection into one- or two- cell stage zebrafish
      embryos. These studies indicated that the mouse Cx43alpha1 promoter can drive
      lacZ expression in neural crest cells in the zebrafish embryos. Analysis by whole
      mount in situ hybridization showed that the endogenous zebrafish Cx43alpha1 gene
      is expressed maternally and zygotically, and expression is observed in regions
      where neural crest cells are found. To further elucidate the developmental
      regulation of Cx43alpha1 gene expression, we screened a zebrafish BAC library and
      identified a clone containing the entire zebrafish Cx43alpha1 gene and flanking
      upstream and downstream sequences. The upstrean Cx43alpha1 promoter sequences
      from zebrafish, mouse, and human were analyzed for evolutionarily conserved DNA
      motifs. Overall these studies suggest that the sequence motifs and
      transcriptional regulation involved in the targeting Cx43alpha1 expression to
      neural crest cells are evolutionarily conserved in zebrafish and mouse embryos.

PMID- 12064605
TI  - Regulated expression of the X. tropicalis connexin43 promoter.
AB  - The spatio-temporal expression pattern of the connexin43 gene during Xenopus
      development has been described (Van der Heyden et al. 2001). To further
      investigate the regulation and function of connexin43 (Cx43) in amphibians, we
      have isolated the gene from Xenopus tropicalis (Xt) and determined its structure.
      The X. tropicalis Cx43 gene displays the typical two exon-one intron connexin
      configuration, where the first exon is non-coding. The predicted amino acid
      sequence of the XtCx43 protein is highly homologous to that of X. laevis, chicken
      and mammals. Expression of XtCx43 cDNA in N2A cells results in gap-junction
      plaque formation. Promoter activity of a 3.5 kb upstream region of the X.
      tropicalis Cx43 gene, including exon 1, mimics endogenous timing of expression
      after injection of reporter constructs in X. laevis embryos.

PMID- 12064606
TI  - Regulation of connexin43 expression by c-fos and c-jun in myometrial cells.
AB  - Labor is associated with a dramatic increase in the myometrial expression of
      connexin43 (Cx43) which is thought to mediate myocyte contractile coupling. The
      transcription factor c-fos is also dramatically increased prior to the onset of
      labor and is therefore a potential regulator of Cx43. The promoter region of Cx43
      contains a conserved activator protein-1 (AP-1) site, which binds dimers of Fos
      and Jun proteins. We constructed expression vectors for c-Fos and c-Jun to
      investigate the role of these transcription factors in the regulation of Cx43
      expression. These expression vectors were then co-transfected into SHM (syrian
      hamster myocyte) cells with a Cx43 promoter-Luciferase vector. The combinations
      of c-Fos and c-Jun proteins activated the Cx43 promoter while c-Jun alone had no
      effect on Cx43 promoter activity. Mutation of the AP-1 site was found to reduce
      this responsiveness. These data indicate that the transcription factors c-Fos and
      c-Jun are important in the regulation of Cx43 expression.

PMID- 12064607
TI  - Connexin26 is regulated in rat urothelium by the scaffold protein IB1/JIP-1.
AB  - Proper function of the wall of bladder requires gap junctional communication for
      coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to
      urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial
      cells, whereas Cx26 expression is restricted to the epithelium. We used a model
      of bladder outlet obstruction, in which a ligature is placed around the urethra
      to increase voiding pressure. Increased fluid pressure was associated with
      increased Cx43 and Cx26 mRNA expression and with the activation of a signaling
      cascade including the transcription factor c-Jun, which is a component of the AP
      1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires
      the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase
      Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine
      retention, we have found a reduced content of IB1/JIP-1 in urothelial cells,
      which in turn induced a drastic increase of JNK and AP-1 binding activities. The
      stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using
      a viral gene transfer approach, a condition which also resulted in a decrease in
      Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates
      in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that
      urothelial Cx26 may be directly regulated by the AP-1 complex.

PMID- 12064608
TI  - Gastrointestinal development in the Drosophila embryo requires the activity of
      innexin gap junction channel proteins.
AB  - Cell to cell communication plays an essential role during pattern formation and
      morphogenesis of the diverse tissues and organs of the body. In invertebrates,
      such as the fruitfly Drosophila, the direct communication of closely apposed
      cells is mediated by gap junctions which are composed of oligomers of the innexin
      family of transmembrane channel proteins. Few data exist about the developmental
      role of the eight innexin genes which have been found in the Drosophila genome.
      We have investigated the role of the innexin 2 and ogre genes during
      gastrointestinal development of the fly embryo. Our findings suggest that
      innexins are involved in the formation of the proventriculus, an organ that
      develops at the foregut/midgut boundary by migration of primordial cells and
      subsequent infolding of epithelial tissue layers.

PMID- 12064609
TI  - Innexins in C. elegans.
AB  - Innexins are functionally analogous to the vertebrate connexins, and the innexin
      family of gap junction proteins has been identified in many invertebrates,
      including Drosophila and C. elegans. The genome sequencing project has identified
      25 innexins in C. elegans. We are particularly interested in the roles that gap
      junctions may play in embryonic development and in wiring of the nervous system.
      To identify the particular C. elegans innexins that are involved in these
      processes, we are examining their expression patterns using specific antibodies
      and translational GFP fusions. In addition we are investigating mutant, RNAi and
      overexpression phenotypes for many of these genes. To date, we have generated
      specific antibodies to the non-conserved carboxyl termini of 5 innexins. We have
      constructed GFP translational fusions for 17 innexins and observed expression
      patterns for 13 of these genes. In total we have characterized expression
      patterns representing 14 innexins. Mutations have been identified in 5 of these
      genes, and at least 3 others have RNAi mutant phenotypes. Generalities emerging
      from our studies include: 1) most tissues and many individual cells express more
      than one innexin, 2) some innexins are expressed widely, while others are
      expressed in only a few cells, and 3) there is a potential for functional pairing
      of innexins.

PMID- 12064611
TI  - N-cadherin and Cx43alpha1 gap junctions modulates mouse neural crest cell
      motility via distinct pathways.
AB  - Our previous studies showed an essential role for connexin 43 or alpha1 connexin
      (Cx43alpha1) gap junctions in the modulation of neural crest cell motility.
      Cx43alpha1 gap junctions and N-cadherin containing adherens junctions are
      expressed in migrating cardiac neural crest cells. Analysis of the N-cadherin
      knockout (KO) mouse model revealed that N-cadherin is essential for gap junction
      mediated dye coupling but not for expression of Cx43alpha1 gap junctions in
      neural crest cells. Time lapse videomicroscopy and motion analysis showed that
      the motility of N-cadherin KO neural crest cells were altered, but the motility
      changes differed compared to Cx43alpha1 KO neural crest cells. These observations
      suggest that the role of N-cadherin in cell motility is not simply mediated via
      the modulation of Cx43alpha1 mediated cell-cell communication. This was confirmed
      by a parallel analysis of wnt-1 deficient neural crest cells, which also showed a
      reduction in dye coupling, and yet no change in cell motility. Analysis of p120
      catenin (p120ctn), an Amardillo family protein known to play a role in cell
      motility, showed that it is colocalized with N-cadherin and Cx43alpha1 in
      migrating neural crest cells. This subcellular distribution was altered in the N
      cadherin and Cx43alpha1 KO neural crest cells. Given these results, we propose
      that N-cadherin and Cx43alpha1 may modulate neural crest cell motility by
      engaging in a dynamic cross-talk with the cell's locomotory apparatus through
      p120ctn signaling.

PMID- 12064610
TI  - Identification of cells expressing Cx43, Cx30, Cx26, Cx32 and Cx36 in gap
      junctions of rat brain and spinal cord.
AB  - We have identified cells expressing Cx26, Cx30, Cx32, Cx36 and Cx43 in gap
      junctions of rat central nervous system (CNS) using confocal light microscopic
      immunocytochemistry and freeze-fracture replica immunogold labeling (FRIL).
      Confocal microscopy was used to assess general distributions of connexins,
      whereas the 100-fold higher resolution of FRIL allowed co-localization of several
      different connexins within individual ultrastructurally-defined gap junction
      plaques in ultrastructurally and immunologically identified cell types. In >4000
      labeled gap junctions found in >370 FRIL replicas of gray matter in adult rats,
      Cx26, Cx30 and Cx43 were found only in astrocyte gap junctions; Cx32 was only in
      oligodendrocytes, and Cx36 was only in neurons. Moreover, Cx26, Cx30 and Cx43
      were co-localized in most astrocyte gap junctions. Oligodendrocytes shared
      intercellular gap junctions only with astrocytes, and these heterologous
      junctions had Cx32 on the oligodendrocyte side and Cx26, Cx30 and Cx43 on the
      astrocyte side. In 4 and 18 day postnatal rat spinal cord, neuronal gap junctions
      contained Cx36, whereas Cx26 was present in leptomenigeal gap junctions. Thus, in
      adult rat CNS, neurons and glia express different connexins, with "permissive"
      connexin pairing combinations apparently defining separate pathways for neuronal
      vs. glial gap junctional communication.

PMID- 12064612
TI  - A neuroprotective role for gap junctions.
AB  - Glial-neuronal interactions have been implicated in both normal information
      processing and neuroprotection. One pathway of cellular interactions involves gap
      junctional intercellular communication (GJIC). In astrocytes, gap junctions are
      composed primarily of the channel protein, connexin43 (Cx43), and provide a
      substrate for formation of a functional syncytium implicated in the process of
      spatial buffering in the CNS. Thus gap junctional communication may be
      neuroprotective following a CNS insult that entails glutamate cytotoxicity (i.e.
      ischemia). We have shown that blocking gap junctions during a glutamate insult to
      co-cultures of astrocytes and neurons results in increased neuronal injury. To
      assess the effect of reduced Cx43 and GJIC on neuroprotection, we examined brain
      infarct volume in wild type and Cx43 heterozygote null mice following focal
      ischemia. Cx43 heterozygous null mice exhibited a significantly larger infarct
      volume compared to wild type. At the cellular level, a significant increase in
      TUNEL positive cells was observed in the penumbral region of the Cx43
      heterozygote mice. These results suggest that augmentation of GJIC in astrocytes
      may contribute to neuroprotection following ischemic injury. These findings
      support the hypothesis that gap junctions play a neuroprotective role against
      glutamate cytotoxicity.

PMID- 12064613
TI  - Gap junctional communication among motor and other neurons shapes patterns of
      neural activity and synaptic connectivity during development.
AB  - We are studying the functional roles of neuronal gap junctional coupling during
      development, using motor neurons and their synapses with muscle fibers as a model
      system. At neuromuscular synapses, several studies have shown that the relative
      pattern of activity among motor inputs competing for innervation of the same
      target muscle fiber determines how patterns of innervation are sculpted during
      the first weeks after birth. We asked whether gap junctional coupling among motor
      neurons modulates the relative timing of motor neuron activity in awake, behaving
      neonatal mice. We found that the activity of motor neurons innervating the same
      muscle is temporally correlated perinatally, during the same period that gap
      junction-mediated electrical and dye coupling are present. In vivo blockade of
      gap junctions abolished temporal correlations in motor neuron activity, without
      changing overall motor behavior, motor neuron activity patterns or firing
      frequency. Together with preliminary studies in mice lacking gap junction protein
      Cx40, our data suggest that developmentally regulated gap junctional coupling
      among motor and other neurons affects the activity in nascent neural circuits and
      thus in turn affects synaptic connectivity. Dynamic monitoring of dye coupling
      can be used to explore this possibility in normal mice and in mice lacking gap
      junction proteins during embryonic and neonatal development.

PMID- 12064614
TI  - Abnormalities in gap junctions and Ca2+ dynamics in cardiomyocytes at the border
      zone of myocardial infarcts.
AB  - Abnormalities in gap junction function and Ca2+ dynamics are believed to be
      important factors in arrhythmogenesis after myocardial infarction. To elucidate
      the relationship between changes in Ca2+ dynamics and gap junctions, we analyzed
      by real-time in situ Ca2+ imaging of fluo-3 loaded whole hearts the
      spatiotemporal occurrence of Ca2+ waves and the localization of connexin43 (Cx43)
      at the border zone of myocardial infarcts induced in the rat by coronary
      ligation. At early time points (2-4 hours postligation), different regions of the
      left ventricle showed distinct changes in cytosolic free Ca2+ concentrations
      [Ca2+]i. While some cardiomyocytes of infarcted regions exhibited high levels of
      resting fluo-3 fluorescence, at border zones frequent Ca2+ waves were observed.
      Some of the waves were abolished by spontaneous Ca2+ transients and others were
      not. Intact myocardium apart from infarcted regions exhibited homogenous Ca2+
      transients. Confocal imaging of Cx43 and actin filaments in the rat heart fixed 2
      hours after coronary ligation revealed that Cx43 was markedly decreased in the
      area of myocyte necrosis with contraction bands and in the neighboring
      myocardium. These results suggest that abnormal expression and function of gap
      junctions could be associated with Ca2+ waves at the border zone of myocardial
      infarcts, possibly through Ca2+ overload.

PMID- 12064615
TI  - Comparison of connexin 43, 40 and 45 expression patterns in the developing human
      and mouse hearts.
AB  - The mouse is currently widely used as a model organism in the analysis of gene
      function but how developmentally regulated patterns of connexin gene expression
      in the mouse compare with those in the human is unclear. Here we compare the
      patterns of connexin expression in the heart during the development of the mouse
      (from embryonic day 12.5 to 6 weeks postpartum) and the human (at 9 weeks
      gestation and adult stage). The extent of connexin43 expression in the ventricles
      progressively increased during development of the mouse heart. The developmental
      pattern of expression for connexins 40 and 45 in the mouse heart was similar, but
      not identical, and in the ventricles showed a progressive and preferential
      expression in the conduction system. In general, these dynamic changes of
      connexins 43, 40 and 45 during mouse cardiac development appear to be mirrored in
      the human.

PMID- 12064617
TI  - Quantifying changes in gap junction structure as a function of lens fiber cell
      differentiation.
AB  - The ocular lens is an ideal model system for studying gap junction structure
      function relationships. Here we apply novel methods to quantitatively compare
      connexin expression over macroscopic distances while simultaneously resolving the
      intracellular distribution of gap junctions in sub-micron detail. Our approach
      has identified three distinct zones of connexin density and allowed changes in
      gap junction plaque size, number and dispersion to be quantified. Our analysis is
      the first to precisely correlate changes in gap junction plaque structure with
      the reported changes in gap junction function that occur as a consequence of
      fiber cell differentiation.

PMID- 12064616
TI  - Conditional gene targeting of connexin43: exploring the consequences of gap
      junction remodeling in the heart.
AB  - Abnormalities in cardiac gap junction expression have been postulated to
      contribute to arrhythmias and ventricular dysfunction. We investigated the role
      of cardiac gap junctions by generating a heart-specific conditional knock-out
      (CKO) of connexin43 (Cx43), the major cardiac gap junction protein. While the
      Cx43 CKO mice have normal heart structure and contractile function, they die
      suddenly from spontaneous ventricular arrhythmias. Because abnormalities in gap
      junction expression in the diseased heart can be focal, we also generated
      chimeric mice formed from Cx43-null embryonic stem (ES) cells and wildtype
      recipient blastocysts. Heterogeneous Cx43 expression in the chimeric mice
      resulted in conduction defects and depressed contractile function. These novel
      genetic murine models of Cx43 loss of function in the adult mouse heart define
      gap junctional abnormalities as a key molecular feature of the arrhythmogenic
      substrate and an important factor in heart dysfunction.

PMID- 12064618
TI  - Use of pIRES vectors to express EGFP and connexin constructs in studies of the
      role of gap junctional communication in the early development of the chick retina
      and brain.
AB  - Control of cell proliferation is vital for the normal development of the neural
      retina. Gap junctional communication has been implicated in the control of
      retinal cell proliferation. We have previously shown that the expression of the
      gap junction protein Connexin 43 closely correlates with the first wave of cell
      proliferation in the retina. Preventing its expression using antisense
      oligonucleotides in the developing eye and surrounding tissues, produces a
      reduction in cell number and the formation of a small eye. In order to examine
      this in more detail we have developed a new means of manipulating connexin
      expression in the developing chick embryo. We have generated pIRES vectors which
      use cyclomegalovirus (CMV) to promote the expression of a green fluorescent
      protein (EGFP) and either wild type Cx43 or a dominant negative form ofthis
      connexin. Following injection ofthese constructs into the ventricles ofthe stage
      10-11 chick embryo they can be incorporated into one side of the chick brain or
      optic vesicle using an electroporation technique, leaving the other side as a
      control. EGFP expression can be seen on the electroporated side of the chick
      brain within 24 hours. Expression of the dominant negative construct in cultures
      of chick limb bud mesenchyme results in total block of cascade blue transfer when
      injected into transfected cells. Expression of both wild type and dominant
      negative constructs in the developing chick retina perturbs the normal
      development of the eye.

PMID- 12064619
TI  - Mouse horizontal cells do not express connexin26 or connexin36.
AB  - Gap junctions between neurons function as electrical synapses, and are present in
      all layers of mammalian and teleost retina. These synapses are largest and most
      prominent between horizontal cells where they function to increase the receptive
      field of a single neuron beyond the width of its dendrites. Receptive field size
      and the extent of gap junctional coupling between horizontal cells is regulated
      by ambient light levels and may mediate light/dark adaptation. Furthermore,
      teleost horizontal cell gap junction hemichannels may facilitate a mechanism of
      feedback inhibition between horizontal cells and cone photoreceptors. As a
      prelude to using mouse genetic models to study horizontal cell gap junctions and
      hemichannels, we sought to determine the connexin complement of mouse horizontal
      cells. Cx36, Cx37, Cx43, Cx45 and Cx57 mRNA could be detected in mouse retina by
      RT-PCR. Microscopy was used to further examine the distribution of Cx26 and Cx36.
      Cx26 immunofluorescence and a beta-gal reporter under regulatory control of the
      Cx36 promoter did not colocalize with a horizontal cell marker, indicating that
      these genes are not expressed by horizontal cells. The identity of the
      connexin(s) forming electrical synapses between mouse horizontal cells and the
      connexin that may form hemichannels in the horizontal cell telodendria remains
      unknown.

PMID- 12064620
TI  - Proliferation, differentiation and apoptosis in connexin43-null osteoblasts.
AB  - Osteoblasts are highly coupled by gap junctions formed primarily by connexin43
      (Cx43). We have shown that interference with Cx43 expression or function disrupts
      transcriptional regulation of osteoblast genes, and that deletion of Cx43 in the
      mouse causes skeletal malformations, delayed mineralization, and osteoblast
      dysfunction. Here, we studied the mechanisms by which genetic deficiency of Cx43
      alters osteoblast development. While cell proliferation rates were similar in
      osteoblastic cells derived from calvaria of Cx43-null and wild type mice,
      camptothecin-induced apoptosis was 3-fold higher in mutant compared to wild type
      osteoblasts. When grown in mineralizing medium, Cx43-null cells were able to
      produce mineralized matrix but it took one week longer to reach the same
      mineralization levels as in normal cells. Likewise, expression of alkaline
      phosphatase activity per cell--a marker of osteoblast differentiation--was
      maximal only 2 weeks later in Cx43-null relative to wild-type cells. These
      observations suggest that Cx43 is important for a normal and timely development
      of the osteoblastic phenotype. Delayed differentiation and increase programmed
      cell death may explain the skeletal phenotype of Cx43-null mice.

PMID- 12064621
TI  - Regulation of lens connexin 45.6 by apoptotic protease, caspase-3.
AB  - Gap junctions are important in maintaining lens homeostasis. Here we report that
      connexin 45.6 (Cx45.6) was partially truncated to a 46 kDa fragment during
      chicken lens development. This specific truncation initiated during embryonic
      days and the truncated fragment accumulated towards the later developmental
      stages. When membranes of the embryonic lens were subjected to caspase-3
      treatment, the 46 kDa fragment of Cx45.6 was reproduced, suggesting apoptotic
      protease caspase-3 is a potential protease involved. The COOH-terminus of Cx45.6
      in GST-fusion protein was also cleaved by caspase-3, confirming that Cx45.6 is a
      direct substrate of caspase-3. Induction of apoptosis in lens primary cultures
      regenerated the 46 kDa fragment and this cleavage was blocked by a caspase-3
      inhibitor. Alteration of amino acid residue Asp364 or Glu367 to Ala prevented
      Cx45.6 from cleavage by caspase-3, suggesting that the cleavage site of Cx45.6 is
      likely to be between Glu367 and Gly361. Phosphorylation of Ser363, a known
      substrate for casein kinase II (CKII) in vivo, inhibited the cleavage of Cx45.6
      by caspase-3. Thus, this study demonstrates that a lens connexin can be a direct
      target of caspase-3 and the cleavage by caspase-3 leads to the development
      associated truncation of Cx45.6. Finally, caspase-3 mediated truncation can be
      modulated by the specific connexin phosphorylation.

PMID- 12064622
TI  - Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK
      pathway: a gap junction-independent action of connexin43.
AB  - Preservation of the mechanosensory function of osteocytes by inhibiting their
      apoptosis might contribute to the beneficial effects of bisphosphonates in bone.
      We report herein a mechanism by which connexin43 hemichannel opening by
      bisphosphonates triggers the activation of the kinases Src and ERKs and promotes
      cell survival. Bisphosphonate-induced anti-apoptosis requires connexin channel
      integrity, but not gap junctions. Osteocytic cells express functional
      hemichannels that are opened by bisphosphonates, as demonstrated by dye uptake,
      regulation by established agonists and antagonists, and cell surface
      biotinylation. The anti-apoptotic effect of bisphosphonates depends on connexin43
      expression in mouse embryonic fibroblasts and osteoblastic cells. Transfection of
      connexin43, but not other connexins, into connexin43 naive cells confers de novo
      responsiveness to the drugs. The signal transducing property of connexin43
      requires the pore-forming, as well as the C-terminal domains of the protein, the
      interaction of connexin43 with Src. and the activation of both Src and ERK
      kinases. These studies establish a role for connexin43 hemichannels in
      bisphosphonate action, and a novel function of connexin43--beyond gap junction
      communication--in the regulation of survival signaling pathways.

PMID- 12064623
TI  - General and conditional replacement of connexin43-coding DNA by a lacZ reporter
      gene for cell-autonomous analysis of expression.
AB  - Using the Cre/loxP system, we have circumvented early postnatal lethality and
      possible pleiotropic effects of general Cx43 gene deletion, in order to determine
      the expression and function of connexin43 (Cx43) in defined cell types. General
      or cell type-specific, Cre-mediated deletion of the floxed (i.e. flanked by loxP
      sites) Cx43-coding region led to activation of the inserted lacZ reporter gene in
      cells with transcriptional activity of the Cx43 gene. As deduced from lacZ
      expression in mice with general deletion, transcriptional activity of the Cx43
      gene was not only found in a broad range of cell types known to a express Cx43,
      but also inpancreatic duct cells and vascular cells of the gut and skeletal
      muscle. Cre-mediated deletion restricted to defined cell types led to lacZ
      activation highlighting corresponding subsets of cells expressing Cx43, such as
      vascular endothelial cells, hepatic duct cells and putative neural crest cells,
      which were otherwise masked by strong Cx43 expression in neighbouring cells. In
      Cx43 expressing cell types, the floxed Cx43 allele was useful as a Cre-excision
      reporter for the characterization of Cre transgenes.

PMID- 12064624
TI  - Cx36 and the function of endocrine pancreas.
AB  - The secretory, duct, connective and vascular cells of pancreas are connected by
      gap junctions, made of different connexins. The insulin-producing beta-cells,
      which form the bulk of endocrine pancreatic islets, express predominantly Cx36.
      To assess the function of this connexin, we have first studied its expression in
      rats, during sequential changes of pancreatic function which were induced by the
      implantation of a secreting insulinoma. We observed that changes in beta-cell
      function were paralleled by changes in Cx36 expression. We have also begun to
      investigate mutant mice lacking Cx36. The absence of this protein did not affect
      the development and differentiation of beta-cells but appeared to alter their
      secretion. We have studied this effect in MIN6 cells which spontaneously express
      Cx36. After stable transfection of a construct that markedly reduced the
      expression of this connexin, we observed that MIN6 cells were no more able to
      secrete insulin, in contrast to wild type controls, and differentially displayed
      a series of still unknown genes. The data provide evidence that Cx36-dependent
      signaling contributes to regulate the function of native and tumoral insulin
      producing cells.

PMID- 12064625
TI  - Frequency dependence of electrical coupling in Deiters' cells of the guinea pig
      cochlea.
AB  - Immunolabeling with antibodies against connexins 26 and 30 showed that, in the
      guinea pig cochlea, supporting Deiters' cells are massively interconnected and
      form an orderly network within the organ of Corti. In paired patch-clamp
      recordings the coupling ratio (CR) of adjacent Deiters' cells at the apex of the
      cochlea (approximately 0.31) was 3-fold smaller than in isolated cell pairs due
      to shunting afforded by multicellular connectivity. With sinusoidal current
      stimuli the delay in signal propagation between adjacent cells increased with
      increasing frequency whereas the amplitude did not change significantly up to 200
      Hz (corner frequency Fc approximately 220 Hz). Depolarizing voltage commands
      applied to an outer hair cell (OHC) elicited outward potassium currents in the
      OHC and inward currents in the abutting Deiters' cells, supplying direct evidence
      for potassium buffering in the organ of Corti. Computational analysis indicates
      that electrical signals injected into a Deiters' cell are transmitted across a
      network segment spanning 8 cell diameters. Thus electrical coupling in the organ
      of Corti is unlikely to influence the selectivity of frequency filtering
      performed mechanically by the mammalian cochlea.

PMID- 12064626
TI  - Human connexin disorders of the skin.

PMID- 12064628
TI  - Connexin 26 expression and mutation analysis in epidermal disease.
AB  - Gap junctional communication has a key role in the co-ordination of keratinocyte
      differentiation. Multiple connexins are expressed in the epidermis and mutations
      in four of these connexins are associated with disorders of keratinisation.
      Specific autosomal dominant Cx26 mutations have been associated with syndromes of
      skin disease and hearing loss. Here we describe the characterization of a new
      Cx26 polyclonal antibody raised against the cytoplasmic region of the protein. It
      has been used to investigate Cx26 protein localization in epidermal disease and
      in the study of mutant Cx26 proteins.

PMID- 12064627
TI  - Cx26 affects the in vitro reconstruction of human epidermis.
AB  - To study the function of connexins in human keratinocytes, we have used a three
      dimensional culture system, in which a tissue is reconstructed using cells from
      the outer root sheet of hair follicles. This tissue reproduces in vitro the
      histological organisation of human epidermis in situ and the normal distribution
      of several keratinocyte markers. Furthermore, it shows characteristics of a
      differentiating epidermis, including the expression of connexin26. Connexin26
      protein expression is increased under physiological and pathological conditions
      resulting in increased keratinocyte turnover. Loss of this protein in
      keratinocytes, obtained from patients carrying a stop mutation, resulted in a
      reduced stratification of the in vitro reconstructed tissue, probably due to a
      lower proliferation and migration capacity of the keratinocytes, although dye
      coupling and persistence of other gap junctions is maintained. No changes were
      seen in tissues reconstructed with keratinocytes from patients carrying a non
      stop mutation of connexin30. The data indicate that, at least in vitro,
      connexin26 affects the function of human keratinocytes, independently of obvious
      changes in coupling.

PMID- 12064629
TI  - Inherited connexin mutations associated with hearing loss.
AB  - One of the most dramatic discoveries in the field of hereditary hearing loss is
      the association of this sensory defect with connexin mutations. Most significant
      is the large proportion, 30-50%, of inherited hearing loss that is due to
      mutations in connexin 26. The proteins these genes encode are expressed in the
      cochlear duct, in regions containing gap junctions. Together, these findings
      suggest a crucial role for gap junction proteins in the mammalian inner ear.
      Mouse models with specific connexin mutations leading to deafness will help
      resolve the many questions regarding the role of these gap junction proteins in
      the inner ear.

PMID- 12064630
TI  - Functional analysis of a dominant mutation of human connexin26 associated with
      nonsyndromic deafness.
AB  - Cx26 has been implicated in dominant (DFNA3) and recessive (DFNB1) forms of
      nonsyndromic sensorineural deafness. While most homozygous DFNB1 Cx26 mutations
      result in a simple loss of channel activity, it is less clear how heterozygous
      mutations in Cx26 linked to DFNA3 cause hearing loss. We have tested the ability
      of one dominant mutation (W44C) to interfere with wild-type human Cx26 (HCx26wt).
      HCx26wt induced robust electrical conductance between paired oocytes, and
      facilitated dye transfer between transfected HeLa cells. In contrast, oocyte
      pairs injected with only W44C were not electrically coupled above background
      levels, and W44C failed to dye couple transfected HeLa cells. Moreover, W44C
      dramatically inhibited intercellular conductance of HCx26wt when co-expressed in
      an equal ratio, and the low levels of residual conductance displayed altered
      gating properties. A nonfunctional recessive mutation (W77R) did not inhibit the
      ability of HCx26wt to form functional channels when co-injected in the same
      oocyte pairs, nor did it alter HCx26wt gating. These results provide evidence for
      a functional dominant negative effect of the W44C mutant on HCx26wt and explain
      how heterozygous Cx26 mutations could contribute to autosomal dominant deafness,
      by resulting in a net loss, and/or alteration, of Cx26 function.

PMID- 12064631
TI  - Aggregated DsRed-tagged Cx43 and over-expressed Cx43 are targeted to lysosomes in
      human breast cancer cells.
AB  - To investigate if either wild-type or aggregated Cx43 is abnormally targeted to
      lysosomes in human breast tumor cells, we examined the fate of DsRed-tagged Cx43
      and over-expressed Cx43 in communication-deficient HBL-100 and MDA-MB-231 cells.
      DsRed-tagged Cx43 was assembled into gap junctions in control normal rat kidney
      cells that express endogenous Cx43 but not in Cx43-negative HBL-100 cells.
      However, when HBL-100 cells were engineered to coexpress wild-type Cx43 a
      population of DsRed-tagged Cx43 was rescued and assembled into gap junctions. Co
      expression of wild-type Cx26 failed to rescue the assembly of DsRed-tagged Cx43
      into gap junctions. Immunolocalization studies revealed that DsRed-tagged Cx43
      was aggregated and partially localized to lysosomes. Interestingly, when human
      MDA-MB-231 breast tumor cells over-expressed wild-type Cx43, Cx43 protein
      primarily localized to lysosomes. Together, these studies provide evidence for
      Cx43 being targeted to lysosomes as a result of misfolding and aggregation, while
      in other cases, the delivery of wild-type Cx43 to lysosomes appears to be due to
      defects innate to the breast tumor cell type.

PMID- 12064632
TI  - Determination of a potential role of the CCN family of growth regulators in
      connexin43 transfected C6 glioma cells.
AB  - Tumour cells often exhibit erratic cell growth, as well as decreased gap
      junctional intercellular communication (GJIC). C6 glioma cells are characterized
      by low levels of gap junction mRNA and protein, and decreased amounts of GJIC
      when compared with astrocytes. Previous work has shown that C6 glioma cells
      transfected with connexin43 (C6-Cx43) exhibit decreased proliferation in vivo and
      in vitro, as well as genes that are differentially expressed between these cells.
      In this study, RNA levels of two CCN (connective tissue growth factor [CTGF],
      Cyr61/Cef-10, nephroblastoma overexpressed [NOV]) gene family members are shown
      to be upregulated in C6-Cx43 cells: Cyr61 and Nov. Cyr61 has previously been
      shown to increase adhesion, migration and growth in many cell types, whereas NOV
      has growth suppressive capacities. Cyr61 RNA expression is shown here to respond
      to serum in quiescent cells in an immediate early gene fashion, independent of
      Cx43 expression. In contrast, Nov RNA levels remain constant, reflective of
      transfected Cx43 expression. Furthermore, confocal microscopy indicates that NOV
      colocalizes with Cx43 plaques at the cell membrane. These findings provide
      insight into the possible role of Nov and Cyr61 in tumour cells.

PMID- 12064633
TI  - Connexin 32 fused to the green fluorescent protein retains its ability to control
      the proliferation of thyroid cells.
AB  - Cell-to-cell exchanges of signaling molecules are thought to be involved in the
      control of cell proliferation. Connexins, which are encoded by a family of genes
      expressed in a cell type-specific manner, are considered as tumor suppressors.
      Thyroid epithelial cells co-express connexin 32 (Cx32) and connexin 43 (Cx43)
      that form distinct and delocalized gap junctions in vivo. The communication
      deficient rat thyroid-derived cell lines, FRTL-5 and FRT, stably transfected with
      the Cx32 cDNA, have a reduced proliferation rate related to a prolonged G1 cell
      cycle phase. To determine whether Cx32-gap junctions exert the same regulatory
      role in vivo, we have undertaken a program of production of transgenic mice over
      expressing Cx32 specifically in thyrocytes. To this purpose, we designed a vector
      in which the Cx32 cDNA was fused to the gene encoding the enhanced green
      fluorescent protein (EGFP) and placed under the control of a strong and thyroid
      specific promoter, the thyroglobulin gene promoter (pTg). In stably transfected
      FRTL-5 cells, the Cx32/EGFP chimeric protein forms functional gap junction
      channels and induces the same proliferation slowdown as native Cx32. The pTg
      Cx32/EGFP construct should thus allow us to obtain the thyroid-targeted over
      expression of Cx32 in the mouse to investigate the involvement of Cx32-gap
      junctions in thyroid growth, functional activity and propensity to form tumors.

PMID- 12064634
TI  - Forensic implications of biting behavior: a conceptually underdeveloped area of
      investigation.
AB  - Within the context of a criminal investigation the human bitemark traditionally
      provides the forensic dentist with both physical and biological evidence. In
      recent years, however, examples exist where in addition to discussing physical
      and biological evidence, expert witnesses have also testified in court regarding
      the behavioral aspects of biting behavior. Interested in this additional source
      of evidence, the authors reviewed the research literature from which biting
      behavior could be explained. The review found a hiatus of empirical knowledge in
      this respect, with only two papers seemingly related to the topic. With this
      dearth of knowledge in mind, the authors present a framework for further analysis
      and tentatively suggest reasons for biting behaviors, using a range of
      psychological models. The article ends with a cautionary note that vague and
      often misleading behavioral assumptions must not be applied to bitemark testimony
      until further data are available.

PMID- 12064636
TI  - Dental participants in mass disasters--a retrospective study with future
      implications.
AB  - Mass casualty incidents continue to require the services of forensic dentists to
      determine the identity of victims. Across North America and Europe. teams of
      forensic dentists train, using mock disaster exercises, to prepare for such
      duties. It is vital that these mock exercises simulate the features of real
      disaster situations as far as possible. In order to inform those responsible for
      the design and implementation of mock exercises, a study was undertaken to
      determine the features of actual disasters that dental personnel had attended.
      Using a questionnaire, data were solicited from 38 odontologists. The average
      number of disasters attended by the respondents was eight, with an average
      casualty number of 94. Aircraft crashes were the most frequent cause of disasters
      that were attended by the odontologists. The authors conclude that future mock
      disaster exercises should replicate features of aircraft crashes as closely as
      possible by using commingled, fragmented, and burned remains. In addition, mock
      disasters should require the identification of a realistic number of individuals
      to ensure authenticity and the maximum logistical preparedness of participants.

PMID- 12064635
TI  - Application of Lamendin's adult dental aging technique to a diverse skeletal
      sample.
AB  - Lamendin et al. (1) proposed a technique to estimate age at death for adults by
      analyzing single-rooted teeth. They expressed age as a function of two factors:
      translucency of the tooth root and periodontosis (gingival regression). In their
      study, they analyzed 306 singled rooted teeth that were extracted at autopsy from
      208 individuals of known age at death, all of whom were considered as having a
      French ancestry. Their sample consisted of 135 males, 73 females, 198 whites, and
      10 blacks. The sample ranged in age from 22 to 90 years of age. By using a simple
      formulae (A = 0.18 x P + 0.42 x T + 25.53, where A = Age in years, P =
      Periodontosis height x 100/root height, and T = Transparency height x 100/root
      height), Lamendin et al. were able to estimate age at death with a mean error of
      +/- 10 years on their working sample and +/- 8.4 years on a forensic control
      sample. Lamendin found this technique to work well with a French population, but
      did not test it outside of that sample area. This study tests the accuracy of
      this adult aging technique on a more diverse skeletal population, the Terry
      Collection housed at the Smithsonian's National Museum of Natural History. Our
      sample consists of 400 teeth from 94 black females, 72 white females, 98 black
      males, and 95 white males, ranging from 25 to 99 years. Lamendin's technique was
      applied to this sample to test its applicability to a population not of French
      origin. Providing results from a diverse skeletal population will aid in
      establishing the validity of this method to be used in forensic cases, its ideal
      purpose. Our results suggest that Lamendin's method estimates age fairly
      accurately outside of the French sample yielding a mean error of 8.2 years,
      standard deviation 6.9 years, and standard error of the mean 0.34 years. In
      addition, when ancestry and sex are accounted for, the mean errors are reduced
      for each group (black females, white females, black males, and white males).
      Lamendin et al. reported an inter-observer error of 9+/-1.8 and 10+/-2 sears from
      two independent observers. Forty teeth were randomly remeasured from the Terry
      Collection in order to assess an intra-observer error. From this retest, an intra
      observer error of 6.5 years was detected.

PMID- 12064637
TI  - Population-specific histological age-estimating method: a model for known African
      American and European-American skeletal remains.
AB  - Previously developed histological age-estimating methods have been based on
      samples lacking interpopulation variability. A comparison of age-associated rib
      histomorphometrics between an European-American sample and an African-American
      sample indicates that ethnicity can have a significant effect on osteon
      population density (OPD), osteon cross-sectional area (On.Ar), and relative
      cortical area (Ct.Ar/Tt.Ar). Based upon these findings, new histological age
      predicting formulae are presented that are recommended when estimating age for
      African-American or European-American skeletal remains. A general formula that is
      applicable to remains of unknown ethnicity is also provided.

PMID- 12064638
TI  - Ecstasy (MDMA) deaths in New York City: a case series and review of the
      literature.
AB  - MDMA ("ecstasy") has gained renewed popularity as a drug of abuse. To access the
      epidemiology and causes of death of MDMA-positive fatalities, all deaths
      investigated by the OCME that tested positive for MDMA (22 deaths) between
      January 1997 and June 2000 were reviewed. There were three deaths in each 1997
      and 1998, eleven in 1999, and five in the first part of 2000. Of these 22 deaths,
      13 were due to acute drug intoxications, 7 due to mechanical injury (blunt
      trauma, gunshot wounds), and 2 due to a combination of natural disease and acute
      drug intoxication. Evidence of recent opiate and/or cocaine use was found in 7 of
      the acute intoxication deaths and in none of the traumatic or combination
      natural/intoxication deaths. The race of all decedents was White between the ages
      of 17-41 years, and 18 of 22 were men.

PMID- 12064639
TI  - The efficiency of an X-ray screening system at a mass disaster.
AB  - This is a study to determine the efficiency and efficacy of using an X-ray
      security screening system to locate both dental fragments and other foreign
      objects that might be commingled with fragmented remains in a mass disaster. A
      controlled study by the Pennsylvania Dental Identification Team (PADIT) revealed
      that a manual examination of simulated body bags containing commingled dental
      parts and foreign objects by a team of trained forensic odontologists was very
      effective in locating dental fragments and in finding foreign objects. Although
      this was effective, it was not efficient, because it was very time consuming.
      With the use of an X-ray security screening system, the time factor could be
      reduced. This study also revealed that even though this sophisticated equipment
      could reduce the time factor in locating commingled dental and foreign objects, a
      forensic odontologist should be utilized to be most effective.

PMID- 12064640
TI  - Suicide by drowning: a 20-year review.
AB  - Drowning as a method of suicide is known to occur, but has primarily been
      described in environments with readily available access to water, such as coastal
      regions. In this study, we describe and analyze a series of suicidal drownings
      occurring in a noncoastal area of Texas. Between 1977 and 1996, 52 cases of
      suicidal drowning were investigated at the Southwestern Institute of Forensic
      Sciences in Dallas, Texas. Such deaths accounted for only 0.85% of all suicides
      and 4% of all drowning deaths. In contrast. suicidal drownings reportedly account
      for 2.8 to 8.9% of all suicides in regions with easy access to water. As with
      other studies of suicidal drowning, the victims are usually sober white males
      over the age of 40 years. Our results also confirm that certain individuals who
      commit suicide by drowning use weights to facilitate the process. A detailed
      analysis of the cases is provided. as is a synopsis of several questions that may
      aid in determining the manner of death in suicidal drowning cases.

PMID- 12064641
TI  - Bodies found in the waterways of New York City.
AB  - We reviewed the case records for all decedents recovered from the waterways of
      New York City over a three year period (1997-2000). The epidemiological profile,
      circumstances, toxicology findings, putrefactive changes, date of recovery,
      length of immersion, and injuries were examined. There were 123 deaths: 52
      suicides, 50 undetermined, 16 accidents, and five homicides. The causes of death
      included: 97 drownings, 13 undetermined, and 13 other. Of all the floating
      decedents, 27% were without putrefactive change. All found after two or more
      weeks of immersion were recovered from November to May. The detection of ethanol
      and illicit drugs was 53% in the accident, 41% in the suicide, and 33% in the
      undetermined groups. Detection of ethanol and/or drugs of abuse is not a reliable
      criterion to distinguish suicide from accident. The identification of the
      deceased is pivotal for determining the manner of these deaths. Therefore, a
      great reliance is placed upon the medical investigator and the police (including
      the missing persons bureau) to determine the circumstances and identification of
      the decedent.

PMID- 12064642
TI  - Time of submergence using aquatic invertebrate succession and decompositional
      changes.
AB  - Pig carcasses were placed in pond and stream habitats in the Malcolm Knapp
      Research Forest in Maple Ridge, B.C. for approximately one year, to examine the
      development, species, and sequence of invertebrates associated with the carrion.
      An invertebrate successional database was created for pond and stream habitats
      for potential use in estimating time of submergence in water related death
      investigations. Analysis has shown that a predictable succession of invertebrates
      colonize the carrion. However, whether or not this succession is carrion
      dependent or seasonal is unknown. There is a difference in the species
      composition between pond and stream habitats. Habitats influence invertebrate
      fauna, therefore, species colonizing carrion are habitat-specific. In both
      habitats, no one organism can determine time of submergence alone.
      Decompositional descriptions from this research were compared with 15 freshwater
      related death investigations. Similarities were seen in the earlier
      decompositional characteristics including bloat, discoloration, and nail
      shedding; however, the human descriptions were so vague that they had little
      value in determining time of submergence and hence time of death.

PMID- 12064643
TI  - Stalking: developing an empirical typology to classify stalkers.
AB  - Stalking has received a great deal of attention from the media and its harmful
      effects on victims have been well documented. Stalking is also more common than
      previously thought, leading researchers to classify stalkers into groups in an
      attempt to predict future behavior. Previous research has grouped stalkers based
      on theoretical models rather than trying to empirically examine stalking
      behaviors along with other factors such as motivation, type of relationship, and
      attachment style in determining a typology of stalkers. Female college students
      (N = 108) who had experienced stalking behaviors responded to questions regarding
      their perceptions of those behaviors. First, these victim perceptions were factor
      analyzed. Then, cluster analysis grouped those factors to produce a four-cluster
      typology of stalkers. Cluster 1 (Harmless) appeared to reflect a more casual,
      less jealous pattern of behavior. Cluster 2 (Low Threat) appeared the least
      likely to become physically violent or threatening, or to engage in illegal
      behaviors. Cluster 3 (Violent Criminal) appeared to be the most likely to engage
      in physically threatening and illegal behaviors. Cluster 4 (High Threat) was
      characterized by a more serious type of relationship and may attempt to be more
      restrictive of their partner when first meeting them.

PMID- 12064644
TI  - Disposition of citalopram in biological specimens from postmortem cases.
AB  - Citalopram is a bicyclic phthalate compound approved in 1998 by the U.S. Food and
      Drug Administration for the treatment of depression. It is a highly selective
      serotonin reuptake inhibitor that appears to have little effect on noradrenaline
      or dopamine reuptake. Since this drug has only recently been released on the U.S.
      market, information regarding therapeutic, toxic, and lethal concentrations is
      sparse. This study reports the detection of citalopram in 22 postmortem cases.
      Citalopram was identified and quantitated by capillary column gas chromatography
      with nitrogen phosphorus detection after basic liquid-liquid extraction.
      Confirmation was achieved by full scan electron impact gas chromatography/mass
      spectrometry. In the 22 cases studied, heart blood citalopram concentrations
      ranged from 0.09 to 1.64 mg/L (n = 22, mean +/- SD = 0.51+/-0.43, median = 0.34);
      femoral blood concentrations ranged from 0.09 to 0.76 mg/L (n = 14, mean +/- SD =
      0.34+/-0.23, median = 0.28); and urine concentrations ranged from 0.05 to 276.00
      mg/L (n = 13). Liver was analyzed in three cases with citalopram concentrations
      ranging from 2.22 to 8.08 mg/kg. The average heart blood/femoral blood ratio was
      1.26 (range 0.75 to 1.98, n = 14). In each case, the cause of death was not
      considered to be related to citalopram toxicity. These data may therefore provide
      a basis for establishing post mortem citalopram concentrations following
      therapeutic doses.

PMID- 12064645
TI  - New formulae for estimating stature in the Balkans.
AB  - Recent studies of secular change and allometry have observed differential limb
      proportions between the sexes, among and within populations. These studies
      suggest that stature prediction formulae developed from American Whites may be
      inappropriate for European populations. The purpose of this investigation is to
      present more appropriate stature prediction equations for use in the Balkans to
      aid present-day identifications of the victims of genocide. The reference sample
      totals 545 white males obtained from World War II data. The Eastern European
      sample totals 177 males and includes both Bosnian and Croatian victims of the
      recent war. Mean stature for Eastern Europeans was obtained from the literature.
      Results show that formulae based on Trotter and Gleser systematically
      underestimate stature in the Balkans. Because Eastern Europeans are taller than
      American Whites it is appropriate to use this as an "informative prior" that can
      be applied to future cases. This informative prior can be used in predictive
      formulae, since it is probably similar to the sample from which the Balkan
      forensic cases were drawn. Based on Bayes' Theorem new predictive stature
      formulae are presented for Eastern Europeans.

PMID- 12064647
TI  - Typing of the locus DYS19 from DNA derived from fingernail clippings using PCR
      Concert rapid purification system.
AB  - DNA extracted from the fingernails of female victims of a violent or aggressive
      act may assist in the identification of the male. Sometimes with the current
      autosomal STR loci, however, the victim's profile may mask the perpetrator's DNA
      profile or the perpetrator's DNA may be substantially lower in quantity than that
      of the victim's DNA. Thus, under these conditions, no characterization is
      possible. In this paper, an alternative DNA extraction procedure was employed,
      and the application of an STR locus residing on the Y chromosome DYS19 was typed
      to allow for genetic characterization of the perpetrator in such cases.

PMID- 12064648
TI  - Photographic evidence protocol: the use of digital imaging methods to rectify
      angular distortion and create life size reproductions of bite mark evidence.
AB  - Bite mark evidence seen in skin injuries or objects is commonly photographed for
      evidentiary documentation, preservation, and analysis. Distortion in forensic
      evidence photographs diminishes the outcome of analytical procedures available to
      the forensic odontologist. Inaccurate positioning of the evidence, camera, or
      measurement reference scale creates perspective and parallax distortion of the
      captured image. These variables must be eliminated, if possible, to ensure
      reliable results derived from comparison of the suspect teeth and the bite mark.
      Detection and measurement of camera/evidence/scale misalignment is the threshold
      step in evidence evaluation, and is possible through digital imaging methods
      coupled with established methods. Correction (rectification) of perspective
      distortion is possible through the application of additional digital editing
      techniques. This study establishes type categories of perspective and parallax
      distortion seen in bite mark evidence, validates the use of the digital imaging
      tools of Adobe Photoshop to correct certain types of distortion, and establishes
      a forensic protocol to verify the accuracy of evidence photographs requiring
      dimensional accuracy.

PMID- 12064649
TI  - Estimation of postmortem interval from hypoxic inducible levels of vascular
      endothelial growth factor.
AB  - Estimation of the postmortem interval (PMI) is one of the most important tasks in
      forensic medicine. Five autopsy organ tissues such as brain, lungs, heart, liver,
      and kidneys were taken at the time of forensic autopsy from 19 known PMI cases
      with a range of postmortem intervals ranging from 1 to 120 h (the mean was 25.81
      h), and the time-course of vascular endothelial growth factor (VEGF) expression
      was measured. The human hepatoma-derived Hep 3B cell line was used as a control.
      The levels of VEGF increased linearly with the PMI up to 20 h in lung (r = 0.95
      and in kidney (r = 0.89), and up to 15 h PMI in liver (r = 0.88). The VEGF levels
      fell after 24 h PMI, and then remained stable. In brain, the levels of VEGF
      started to increase after 24 h PMI and increased linearly with PMI up to 40 h in
      brain (r = 0.94) and then begin to fall. In heart, there was no clear correlation
      between the PMI and VEGF level. Some variations occurred in selected cases, such
      as the infant and asphyxial deaths. In conclusion, measurement of hypoxia
      inducible levels of VEGF in various body organs appears to be a useful method of
      estimating the PMI up to 24 h in forensic medicine and pathophysiology. This
      method is also probably applicable in ischaemia in clinical and basic medicine.

PMID- 12064650
TI  - A test of the phenice method for the estimation of sex.
AB  - The Phenice method for the estimation of sex of an individual from the pelvis was
      tested on 198 individuals of known sex from the Terry collection by an individual
      with training in the technique, but no additional training in forensic
      anthropology. Sex was correctly estimated in 88.4% of all individuals and more
      accurately estimated in females than in males. In a subsequent test of the same
      individuals by the same investigator utilizing additional nonmetric pelvic
      indicators, overall accuracy increased to 96.5%, with slightly greater accuracy
      for males. The study suggests that experience likely contributes to the accuracy
      of the Phenice method and that for inexperienced investigators, consultation of
      all pelvic indicators offers an advantage over using just the three variables in
      the Phenice method.

PMID- 12064653
TI  - Unexpected death due to infectious mononucleosis.
AB  - A 14-year-old boy with infectious mononucleosis died unexpectedly in hospital.
      The most significant finding at autopsy was the presence of marked bilateral
      tonsillar enlargement with considerable narrowing of the upper airway. There were
      no other underlying organic diseases that could have caused or contributed to
      death. Narcotic analgesia had been administered less than 2 h before death and
      may have contributed to respiratory compromise. The blood morphine level was 0.08
      mg/L. Toxicological evaluation of individuals with obstructive lesions of the
      upper airway may, therefore, be a useful adjunct to the autopsy assessment of
      such cases as it may reveal factors exacerbating mechanical blockage.

PMID- 12064654
TI  - Deaths associated with liposuction: case reports and review of the literature.
AB  - Tumescent liposuction is a common cosmetic procedure that is performed as an
      outpatient service in physician's offices and is largely believed to be safe. The
      protuberant areas of the body containing the undesirable fat deposits are
      injected with normal saline containing lidocaine and epinephrine for pain control
      and hemostasis, and the waterlogged cells are suctioned out via cannula through a
      small incision. We recently encountered three cases in which deaths were
      attributed to this procedure. Two showed fat embolization in the lung and one
      died from fluid overload. The osmium tetroxide post-fixed lung sections showed
      fat emboli in the interstitial capillaries and arterioles. We reviewed the recent
      literature and found that pulmonary thromboemboli, fat embolization, fluid
      overload, and lidocaine and epinephrine intoxication are found at autopsy in many
      cases. Forensic pathologists responsible for determining the cause and manner of
      death should become familiar with the postmortem findings and risks of
      liposuction therapy and communicate them to their clinical colleagues and
      communities.

PMID- 12064655
TI  - A fatal case of cocaine poisoning in a body packer.
AB  - A 27-year-old man was carrying in his digestive tract 99 packages each containing
      about 10 g of a 86% cocaine powder. The courier died by acute cocaine
      intoxication due to inflation and rupture of four packages during a flight from
      Bogota to Rome. At the autopsy, the external examination was unremarkable. The
      internal examination showed edema and generalized congestion of the organs.
      Toxicological analyses were performed by gas chromatography-mass spectrometry
      after solid phase extraction using Bond Elut Certify columns and derivatization
      with BSTFA/TMCS. High levels of cocaine and benzoylecgonine were found in blood
      (4.0 microg/mL and 17.0 microg/mL), urine (152.0 microg/mL and 512.0 microg/mL),
      bile (99.8 microg/mL and 54.0 microg/mL), vitreous humor (7.1 microg/mL and 5.8
      microg/mL), brain (7.5 microg/mL and 3.5 microg/mL), and hair (55.5 ng/mg and
      27.7 ng/mg). The presence of the cocaine and its metabolite in the hair suggested
      that the man was a cocaine user.

PMID- 12064656
TI  - Hair analysis of seven bodybuilders for anabolic steroids, ephedrine, and
      clenbuterol.
AB  - Several bodybuilders, all winners of international competitions, were arrested
      for trafficking of a number of doping agents including anabolic steroids,
      ephedrine, beta-adrenergics, human chorionic gonadotropin, antidepressants, and
      diuretics. In accordance with the recent French law against doping, the judge
      asked to test seven bodybuilders to identify doping practices. Hair and urine
      specimens were collected for analysis. After decontamination, a 100 mg hair
      strand was pulverized in a ball mill, hydrolyzed, extracted, and derivatized to
      be tested by GC/MS for anabolic steroids, beta-adrenergic compounds, ephedrine,
      and other doping agents. Urine was analyzed for anabolic steroids and
      metabolites, beta-adrenergic compounds, ephedrine, and human chorionic
      gonadotropin, in addition to a broad spectrum screening with GC/MS. The following
      compounds were detected in urine: ephedrine (29 and 36 ng/mL, n = 2), clenbuterol
      (0.2 to 0.3 ng/mL, n = 3), norandrosterone (4.7 to 100.7 ng/mL, n = 7),
      norethiocholanolone (0.9 to 161.8 ng/mL, n = 6), stanozolol (1 to 25.8 ng/mL, n =
      4), methenolone (2.5 to 29.7 ng/mL, n = 4), testosterone (3 to 59.6 ng/mL, n =
      7), epitestosterone (1 to 20.4 ng/mL, n = 7) and ratio
      testosterone/epitestosterone >6 for four subjects (18.5 to 59.6). The following
      drugs were detected in hair: ephedrine (0.67 and 10.70 ng/mg, n = 2), salbutamol
      (15 to 31 pg/mg, n = 3), clenbuterol (15 to 122 pg/mg, n = 6), nandrolone (1 to
      7.5 pg/mg, n = 3), stanozolol (2 to 84 pg/mg, n = 4), methenolone (17 and 34
      ng/ml, n = 2), testosterone enanthate (0.6 to 18.8 ng/mg, n = 5), and
      testosterone cypionate (3.3 to 4.8 ng/mg, n = 2). These results document the
      doping practice and demonstrate repetitive exposure to anabolic compounds and
      confirm the value of hair analysis as a complement to urinalysis in the control
      of doping practice.

PMID- 12064658
TI  - Identification of decomposed human remains from radiographic comparisons of an
      unusual foot deformity.
AB  - A case of positive identification from decomposed human remains using an unusual
      foot deformity is presented. Scrutiny of the decedent revealed foot deformities,
      which upon examination, prompted further inquiry. Radiographic comparisons and
      defleshing each foot established bilateral talipes equinovarus (TEV, clubfoot).
      Positive identification was based upon unique skeletal features present in the
      radiographs.

PMID- 12064657
TI  - Typing Y chromosome STR haplotypes using redesigned primers.
AB  - A panel of Y-specific STR loci, including DYS19, DYS389, DYS390, DYS391, DYS392,
      and DYS393 was analyzed using horizontal nondenaturing polyacrylamide gel
      electrophoresis with a discontinuous buffer system (horizontal disk-PAGE). In
      order to obtain correct results for the larger DYS389 and DYS392 alleles, it was
      necessary to design new primers that bind closer to the repeat region and lead to
      a significant reduction of the amplified fragment size. Using the modified primer
      sets the horizontal disk-PAGE results were consistent with a nondenaturing
      approach using fluorescent primers and a 377 automated sequencer. The modified
      procedure also amplifies the second repeat stretch at the duplicated DYS389 locus
      as a single fragment, which results in an immediate allele identification. The
      results indicate that horizontal disk-PAGE with silverstaining is a simple
      approach to type the recommended Y-specific STR markers.

PMID- 12064659
TI  - Detection of ketosis in vitreous at autopsy after embalming.
AB  - Ketosis occurs in ketoacidosis or malnourishment. When either is suspected in
      relation to a death, it may be important to analyze for ketosis at autopsy. We
      encountered a case where starvation was suspected in a deceased nursing home
      resident, where the body had been embalmed prior to autopsy. Gas chromatography
      (GC) was unable to separate acetone from formaldehyde, a component of embalming
      fluid. The Acetest is a simple test that can detect acetone and acetoacetate in
      body fluids. We validated the Acetest with GC on vitreous. The Acetest and GC
      were consistent except at very low levels of acetone or acetoacetate. The
      sensitivity of the Acetest for acetoacetate in vitreous was 10 mg/dL, consistent
      with early starvation. Significant interference from embalming fluid did not
      occur. The Acetest was negative in the described case. The Acetest is a simple
      and useful test for the detection of ketosis in embalmed autopsies.

PMID- 12064660
TI  - Three Y-chromosome STR frequencies in a population from equatorial Guinea
      (Central Africa).

PMID- 12064661
TI  - Allele frequency distribution for nine fluorescent based STR loci in Tamil
      population (South India).

PMID- 12064662
TI  - Population data on the three STR loci in the upper Silesia (Poland).

PMID- 12064663
TI  - Allele frequency distribution of two minisatellite loci (D19S20 and apoB 3' VNTR)
      among five distinct population groups of India.

PMID- 12064665
TI  - Commentary on: Rompen JC, Meek MF, van Andel MV. A cause celebre: the so-called
      "ballpoint murder." J Forensic Sci 2000;45(5): 1144-1147.

PMID- 12064664
TI  - Haplotype frequencies for two new Y-STR loci in Chinese population.

PMID- 12064666
TI  - Variation in midfacial tissue thickness of African-American children.
AB  - Forensic anthropologists use facial reconstruction to develop a likeness of an
      unknown individual in order to generate public interest that may lead to a
      positive identification. Tissue thicknesses of the face from living persons or
      cadavers are an essential part of the reconstruction method. The purpose of this
      study is to add to the growing database of tissue thicknesses along the facial
      midline of African-American children and to begin to examine the possibility of
      geographic differences between children of the same ancestral group. Results
      indicate that significant differences do not exist between males and females or
      between African-American females from the Midwest and Southeast U.S. Only age was
      determined to have a significant effect on mean tissue thickness variation, in
      our sample, with the majority of change occurring in the facial region.

PMID- 12064667
TI  - Jonestown tragedy revisited: the role of dentistry.
AB  - The authors record the contribution of dentistry to the identification of victims
      of one of the most significant tragedies of the 20th century--the mass suicide of
      members of a religious cult, which initially resulted in 913 deaths and
      ultimately in 923. Though forensic dentistry played a significant part in
      identifying victims, the only report by members of the United States
      identification team did not examine dentistry's valuable role. Furthermore, the
      dental-investigation aspects have been mentioned merely in passing by the news
      media despite an infinite number of stories on the tragedy ranging from factual
      to expose. The dental team's organization, methodology, and significant
      contributions to forensic dentistry and a variety of remarkable problems that the
      team encountered and the lessons learned from them are documented in this paper.

PMID- 12064668
TI  - Age estimation by measuring the racemization of aspartic acid from total amino
      acid content of several types of bone and rib cartilage: a preliminary account.
AB  - Age estimation has been often performed based on the rate of aspartic acid
      racemization using bones. In this study, we investigated various kinds of bone
      and a cartilage for suitability to estimate age by racemization. Ten male
      cadavers aged 22 to 77 years at death were selected, and bone specimens and
      cartilage were taken from seven sites in each individual. The rate of
      racemization of aspartic acid among total amino acid contained in each specimen
      was analyzed by gas chromatography. The correlation coefficient between the rate
      of racemization and chronological age was relatively high in the sternum, skull,
      and femur. The rates of aspartic acid racemization were high in the costal
      cartilage, femur, and skull. In addition, we found that the rate of racemization
      was only slightly lower after the second irrigation than after the first
      irrigation in femur and skull bone specimens, but those of others were
      significantly lower. These findings showed that among the six different bones and
      rib cartilage, the skull and femur might be used most effectively for age
      estimation using total amino acid fraction.

PMID- 12064671
TI  - Constructing universal multiplex PCR systems for comparative genotyping.
AB  - Analysis of length polymorphisms at STR loci in the human genome has become a
      standard approach for comparative genotyping in many areas including disease
      research and diagnostics, parentage assessment, investigations of human
      diversity, and forensic science. The simultaneous analysis of multiple STR loci
      through multiplex PCR and multicolor fluorescence detection offers sample
      conservation, high throughput, and automated genetic analysis. Careful design and
      optimization of tetranucleotide STR multiplexes has led to reliable, standardized
      systems that powerfully differentiate and distinguish individual human DNA
      profiles. The development of these multiplex systems involved a rigorous
      experimental strategy that included careful selection of PCR primer sequences
      (for yield, specificity, and multiplex compatability), along with optimization of
      PCR component concentrations, thermal cycling parameters, and fluorescence
      detection conditions. This developmental approach rendered well-characterized DNA
      typing systems that are high performing (sensitive, specific, and balanced),
      optimized to universal parameters (same reaction conditions), resilient to
      fluctuations in reaction conditions, and simple to implement and use routinely.

PMID- 12064673
TI  - Mandibular ramus height as an indicator of human infant age.
AB  - There were two goals to be achieved from the analysis of 53 skeletonized infants
      from the Southwest Collection at the National Museum of Natural History. The
      first objective was to determine whether this infant sample could be aged based
      on a mandibular measurement. The second was to determine which dimension of the
      mandible, if any, most accurately predicts infant age within a six-month range.
      Seven osteometric measurements were applied to each mandible. Statistical
      analysis determined that the individuals in the Smithsonian's Southwest
      Collection that were under two-years-old could be accurately aged to within six
      months. Out of these seven measurements the most accurate age-at-death estimates
      were generated based on the maximum height of the mandibular ramus. This finding
      can potentially aid investigators in determining the age-at-death of infants.

PMID- 12064672
TI  - TWGDAM validation of AmpFlSTR PCR amplification kits for forensic DNA casework.
AB  - Laboratory procedures used in short tandem repeat (STR) analysis were subjected
      to various scenarios that assessed reliability and identified potential
      limitations. These validation studies were designed as recommended by the
      Technical Working Group on DNA Analysis Methods (TWGDAM) and the DNA Advisory
      Board (DAB) (17,18). Various DNA samples were amplified by the polymerase chain
      reaction (PCR) using AmpFlSTR PCR Amplification Kits (i.e., AmpFlSTR Green I,
      Profiler, Profiler Plus, and COfiler kits), detected with ABI Prism
      instrumentation, and analyzed using GeneScan and Genotyper software. Data
      acquired in these studies reinforced an existing body of knowledge and expertise
      regarding application and interpretation of STR typing in the forensic science
      community. Consistent STR genotypes were detected in various body tissues and
      fluids. Inter-laboratory comparisons produced concordant genotype results.
      Quantitative interpretational aids for DNA mixtures were characterized. Ability
      of the typing systems to type potentially compromised samples reliably was
      evaluated. Nonprobative case evidentiary DNA was successfully amplified,
      genotyped, and interpreted. Potential limitations or cautionary factors in the
      interpretation of minimal fluorescence intensity were demonstrated. Differential
      amplification between loci was observed when PCR was inhibited; preferential
      amplification typically was not. Single AmpFlSTR locus amplification did not
      offer consistent benefit over AmpFlSTR multiplexing, even in cases of DNA
      degradation or PCR inhibition. During rigorous evaluation, AmpFlSTR PCR
      Amplification Kits reproducibly yielded sensitive and locus-specific results, as
      required in routine forensic analyses.

PMID- 12064675
TI  - Spiral computed tomography of pulmonary embolism.
AB  - Within the last several years, spiral computed tomography angiography (SCTA) of
      the pulmonary arteries has emerged as a noninvasive angiographic modality for the
      evaluation of patients with suspected pulmonary embolism (PE). SCTA is based on
      continuous computed tomography (CT) data acquisition during patient transport
      through the rotating X-ray tube and detector system, where scanning is performed
      in the time period in which the injected contrast material passes through the
      pulmonary arteries. Single detector spiral CT has a sensitivity of approximately
      85-90% and a specificity between 88-95%. Sensitivity and specificity are very
      likely to increase with the use of multidetector spiral CT scanners that allow
      scanning of large lung volumes with a scan collimation as narrow as 1 mm.
      Currently, SCTA is most commonly used as a primary imaging method in patients
      with suspected PE, and as a second-line method in cases with inconclusive
      ventilation/ perfusion scintigraphy results. SCTA has proven to be cost
      effective, especially in combination with ultrasound of the lower extremities.
      Limitations of the method include a decreased sensitivity for the detection of
      small isolated clots in the peripheral pulmonary arterial bed, and a potentially
      reduced image quality in patients with coexistent cardiopulmonary disorders.
      Despite these limitations, several studies have now documented that, in patients
      with suspected pulmonary embolism, it is safe to withhold anticoagulation therapy
      if a spiral computed tomography exam of the pulmonary arteries is negative and no
      lower extremity venous thrombosis is present. In the future, multislice computed
      tomography scanning of the pulmonary arteries with multiplanar reformation and
      one-stop shopping, i.e. scanning of the pulmonary arteries and the lower
      extremity veins in a single session, will further enhance the role of computed
      tomography angiography in the examination of patients with suspected pulmonary
      embolism.

PMID- 12064676
TI  - Imaging in lung disease.

PMID- 12064677
TI  - Modern treatment of pulmonary embolism.
AB  - Modern treatment of acute pulmonary embolism requires rapid and accurate
      diagnosis followed by risk stratification to devise an optimal management
      strategy. Patients at low risk have good outcomes simply with intensive
      anticoagulation treatment. Higher-risk patients may require more aggressive
      intervention with thrombolysis or embolectomy. Clinical risk factors for an
      adverse outcome include increasing age, cancer, congestive heart failure,
      systemic arterial hypotension, chronic obstructive pulmonary disease and right
      ventricular dysfunction. A promising approach is the Geneva Prognostic Score,
      which is based upon a rapid clinical assessment. On physical examination, signs
      of right ventricular failure, including distended jugular veins and a right-sided
      S3 gallop, should be looked for. The electrocardiogram may show evidence of right
      ventricular strain with a new right bundle branch block or T wave inversion in
      leads V1-V4. The troponin level may be elevated as a marker of cardiac injury and
      right ventricular microinfarction, even in the absence of coronary artery
      disease. The most useful imaging marker of high risk is the presence of moderate
      or severe right ventricular dilatation and hypokinesis on the echocardiogram,
      especially with progressively worsening right ventricular function despite
      intensive anticoagulation treatment. Patients at high risk should be considered
      for thrombolytic therapy or embolectomy rather than management with
      anticoagulation therapy alone. Special care must be taken to avoid thrombolytic
      therapy among patients who might be susceptible to intracranial haemorrhage.
      Intracranial haemorrhage reached a surprisingly high rate of 3.0% in the
      International Cooperative Pulmonary Embolism Registry of 2,454 prospectively
      evaluated acute pulmonary embolism patients at 52 hospitals in seven countries.
      An alternative approach to patients at high risk is a catheter-based or open
      surgical embolectomy. It is crucial to refer these patients as quickly as
      possible, rather than delaying intervention until cardiogenic shock has ensued.
      Fortunately the current tools for risk stratification provide an "early window"
      for prognostication and can help the coordination of a definitive treatment plan
      with optimal results.

PMID- 12064678
TI  - Imaging techniques in treatment algorithms of pulmonary embolism.
AB  - Pulmonary embolism (PE) is more often diagnosed post mortem by pathologists than
      in vivo by clinicians. The identification of practical diagnostic algorithms
      could reduce the rate of diagnoses first made at autopsy. The literature was
      reviewed for evidence-based approaches to PE diagnosis. Since the PE mortality
      rate greatly exceeds that of deep vein thrombosis (DVT), more emphasis was given
      to reports specifically dealing with PE diagnosis by objective pulmonary vascular
      imaging techniques than to those aimed at DVT detection. Several studies have
      shown that standardized clinical estimates can be effectively used to give a
      pretest probability to calculate, after appropriate objective testing, the post
      test probability of PE. A prospective trial has shown that perfusion scanning,
      rather than ventilation/perfusion scanning, should be the imaging technique of
      first choice for the management of patients suspected of having PE. The clinical
      usefulness of spiral computed tomography has not as yet been firmly established.
      However, ongoing technological developments would probably render the technique
      accurate enough to replace conventional angiography. The authors propose a
      noninvasive diagnostic algorithm with high predictive accuracy (positive
      predictive value 96%; negative predictive value 98%) starting with a standardized
      assessment of clinical likelihood, followed by a perfusion scan and, eventually,
      spiral computed tomography in only a minority of patients (< 20%) with discordant
      clinical and scintigraphic findings.

PMID- 12064679
TI  - Computed tomography and magnetic resonance imaging: past, present and future.
AB  - The aims of this paper are to summarize the current recommendations for the use
      of computed tomography (CT) and magnetic resonance imaging (MRI) in the chest and
      to suggest some possible future developments. The main developments of CT in the
      chest have been the introduction of high-resolution CT (HRCT), spiral CT and,
      more recently, multidetector spiral CT. HRCT is defined as thin-section CT (1- to
      2-mm collimation scans), optimized by using a high-spatial resolution (edge
      enhancing) algorithm. Several studies have shown that HRCT closely reflects
      macroscopic (gross) pathological findings. HRCT currently has the best
      sensitivity and specificity of any imaging method used for the assessment of
      focal and diffuse lung diseases. The advent of spiral CT and, more recently,
      multidetector CT scanners, has allowed for major improvements in the imaging of
      airways, pulmonary and systemic vessels, and lung nodules. Spiral CT facilitates
      multiplanar and three-dimensional display of structures and visualization of
      pulmonary and systemic vessels, with a level of detail that is comparable to that
      of conventional angiography. With the use of graphics-based software programs,
      spiral CT enables depiction of the luminal surface of the airways with images
      that resemble those of bronchoscopy (virtual bronchoscopy) or bronchography
      (virtual bronchography). Several studies have shown a high sensitivity and
      specificity for spiral CT in the diagnosis of acute pulmonary embolism.
      Therefore, spiral CT is rapidly becoming the imaging modality of choice in the
      diagnosis of pulmonary embolism. Like the radiograph, signal intensity on
      computed tomography is mainly due to a single parameter: electron density. The
      signal intensity of the magnetic resonance image depends on four parameters:
      nuclear density, two relaxation times called T1 and T2, and motion of the nuclei
      within the imaged lung volume. Abnormal soft tissue can be identified more easily
      through measurement of these four parameters than through use of computed
      tomography. Furthermore, because the spatial orientation of the image is
      determined by manipulation of magnetic fields, scans can be performed in any
      plane. The main indications for magnetic resonance in the chest have been in the
      evaluation of the heart, major vessels, mediastinum, and hilar structures because
      of the natural contrast provided by flowing blood. Of particular interest for the
      respirologist has been the recent development of magnetic resonance angiography.
      This technique consists of three-dimensional single breath-hold images obtained
      using gadolinium-based contrast agents. This is a promising technique for the
      diagnosis of acute and chronic pulmonary embolism.

PMID- 12064680
TI  - Computed tomography in staging for lung cancer.
AB  - Computed tomography (CT) provides the most detailed imaging information, hence it
      is generally used as a routine imaging procedure in the tumour, node, metastasis
      (TNM)-staging of patients with lung cancer. However, despite the continuously
      ongoing process of improvement in CT scanning in which today's CT scanners
      combine fast acquisition, fast data reconstruction and high detail, the technique
      has important limitations. CT can, in some cases, very accurately show tumour
      extent within, and predict spread beyond the lung. However, the question of
      whether the tumour has invaded the chest wall or the mediastinum and, if so,
      whether it is still potentially surgically curable often remains unanswered. In
      addition, the only sign for predicting lymph node involvement using CT is
      enlargement. Many studies have shown that this sign is not very reliable. CT is
      also, with success, being used to evaluate distant metastases although other
      techniques such as ultrasound and magnetic resonance imaging can have similar or
      higher accuracies. Despite these well-known limitations, computed tomography will
      most likely stay the routine imaging procedure for determining resectability and
      for assessing intra- and extrathoracic spread of lung cancer. The improvement in
      technology will probably result a better T-staging. The role of computed
      tomography in nodal staging remains important. It offers the surgeon a road map
      of the lymph nodes and guides towards the nodes that need biopsy. Combining
      computed tomography with positron emission tomography, when it becomes more
      widely available, will add functional images to the detail of computed tomography
      and will not only improve nodal staging but will probably also allow a better
      evaluation of distant metastasis and reduce the number of unnecessary
      interventional procedures.

PMID- 12064681
TI  - Imaging in lung cancer: positron emission tomography scan.
AB  - In the past 5 yrs, positron emission tomography (PET), usually used with 18F
      fluoro-2-deoxy-glucose (FDG), has become an important imaging modality in lung
      cancer patients. Currently, the use of FDG-PET in respiratory oncology is mainly
      for diagnosis and staging. Standard indications are the evaluation of an
      indeterminate solitary pulmonary nodule or mass, where FDG-PET has proven to be
      significantly more accurate than computed tomography (CT) in the distinction
      between benign and malignant lesions. Several studies have also convincingly
      demonstrated that locoregional lymph node staging by FDG-PET (in correlation with
      CT images) is significantly superior to CT, with a negative predictive value
      equal or even superior to mediastinoscopy. FDG-PET also improves extrathoracic
      staging, through the detection of lesions missed at conventional imaging or
      characterization of lesions that remain equivocal on conventional imaging. Many
      European countries now have or plan reimbursement in these indications. Large
      scale randomized studies should now focus on the impact this accurate tumour
      imaging technique has on treatment outcome and cost-efficacy. Ongoing studies in
      specialized centres focus on the use of FDG-PET in more advanced clinical
      applications, such as planning radiotherapy, response evaluation after
      radiotherapy or (induction) chemotherapy, follow-up and early detection of
      recurrence, and prognostic information in this in vivo measurement of tumour
      glucose metabolism. After a short note on the technique used and a summary of the
      current common indications of diagnosis and staging, this paper will deal mainly
      with two of the more advanced clinical applications of FDG-PET in locally
      advanced nonsmall cell lung cancer: radiation treatment planning and assessment
      of induction chemotherapy. Finally, it should be mentioned that a whole new field
      of applications of positron emission tomography in molecular biology, using new
      radiopharmaceutical probes, is under extensive investigation. These techniques
      are promising for future use in very early response monitoring during chemo- or
      radiotherapy, in evaluation of novel molecular-targeted lung cancer therapies, or
      even gene therapy.

PMID- 12064682
TI  - Current surgical treatment of nonsmall cell lung cancer 2001.
AB  - Recognizing that surgical treatment is still the best option for controlling lung
      cancer, surgeons want an operation to be performed when the benefits clearly
      outweigh the possible risks, and when it has been determined that cancer
      resection is the most appropriate course of management. The necessity for a
      compulsive attitude toward preoperative assessment is therefore to be emphasized.
      Approximately 45% of all lung cancers are limited to the chest, where surgical
      resection is the most effective method of controlling the disease. Patients with
      tumour (T) 1, node (N) 0 and T2N0 tumours have early lung cancer, and most are
      curable by resection, with 5-yr survival rates in the range 75-80% for patients
      with T1N0 status. The "gold standard" of surgery remains lobectomy. Stage T1N1
      and T2N1 carcinomas represent a group of patients in whom the disease involves
      hilar and bronchopulmonary nodes. This group is best treated by complete
      resection and mediastinal lymphadenectomy. Survival data following surgical
      resection of T3 tumours clearly show better survival in patients with T3N0
      disease than in those with T3N1-2 disease. Five-year survival rates for
      completely resected T3N0 lesions are in the range 30-50%. Once N1 disease is
      present, survival decreases to 15-20%. Incomplete resections fail to cure and
      surgery is not indicated if N2 disease is documented preoperatively. On occasion,
      T4 tumours involving the carina or vertebral body can be completely resected but
      T4N1-2 lesions are virtually incurable by surgery. The presence of mediastinal
      lymph node metastasis (N2/N3 disease) is an ominous prognostic sign and stage III
      b disease, by virtue of metastatic contralateral nodes, is an absolute
      contraindication to surgical resection. Induction treatments with chemoradiation
      have shown prolongation of survival and three randomized trials have demonstrated
      a survival advantage over surgery alone.

PMID- 12064683
TI  - New imaging techniques in the treatment guidelines for lung cancer.
AB  - Computed tomography (CT) remains the main imaging technique for the preoperative
      staging and post-therapeutic evaluation of bronchogenic carcinoma. Spiral CT has
      already overcome some of the problems encountered with central or more extensive
      tumours. Multislice CT offers further improvement and allows for scanning of the
      whole chest within a single breath-hold using a thin-section high-resolution
      technique. Problem-adapted sections in arbitrary directions become available and
      provide an excellent spatial resolution. One can expect improved accuracy for the
      evaluation of transfissural tumour growth, chest wall involvement, mediastinal
      infiltration and lymph node staging. Despite recent advances in magnetic
      resonance (MR) techniques for imaging the chest, the role of MR for staging of
      bronchogenic carcinoma remains limited. It offers advantages such as the
      assessment of chest-wall involvement or mediastinal involvement in patients in
      whom CT remains equivocal. Lymph-node-specific MR contrast agents offer new
      diagnostic potential for the assessment of metastatic disease. New techniques for
      the display of three-dimensional data sets include volume rendering and virtual
      bronchoscopy. These techniques represent new tools for the evaluation and
      demonstration of pathology within the central tracheobronchial tree. Their most
      important application is the guidance of bronchoscopic biopsies. The assessment
      of an indeterminate pulmonary nodule is frequently based on positron emission
      tomography imaging. As an alternative, nodule vascularization (contrast
      enhancement patterns on CT or magnetic resonance imaging (MRI)), calcifications
      (absorption characteristics at various X-ray energies on CT or dual energy
      radiography), and morphological features (high resolution imaging at CT) can be
      used as the basis for nodule differentiation. The dynamics of contrast
      enhancement in CT or MRI can also be used for the assessment of tumour viability
      after chemotherapy. Lung cancer screening programmes are still controversial. Low
      dose computed tomography scanning and computed assisted detection algorithms
      based on chest radiographs or computed tomography scans form the technical basis
      for such projects.

PMID- 12064684
TI  - No advantage of treating acute respiratory tract infections with azithromycin in
      a placebo-controlled study.
AB  - Acute respiratory tract infection (ARTI) is the commonest reason for which
      antibiotics are prescribed, despite the fact that ARTI is mostly of viral origin.
      The effectiveness of antibiotics in these illnesses is, at best, questionable.
      Jordan is a developing country where bacterial infections are thought to be more
      common than in developed countries and initially viral illnesses are frequently
      superimposed by bacterial infections. The present study represents an attempt to
      assess whether routine antibiotic treatment of ARTI has any beneficial effect on
      the course of the illness. The study was conducted in northern Jordan between 1
      June and December 14, 2000. Patients > or =8 y of age visiting either of 2 health
      centers and diagnosed by the physician with ARTI above the level of the
      bronchioles were assigned on an alternating basis to receive either azithromycin
      or placebo. Patients were assessed at their initial visit and were subsequently
      followed up after 3 d, 1 week and 2 weeks. A total of 185 patients were included
      in the study. Patients administered azithromycin or placebo did similarly in
      terms of the proportions improved or cured and the duration of illness. We
      conclude that routine use of antibiotics (azithromycin) in ARTI is unlikely to
      alter the course of the illness.

PMID- 12064685
TI  - Prevalence of Campylobacter concisus in diarrhoea of immunocompromised patients.
AB  - The importance of Campylobacter species other than C. jejuni/coli in diarrhoeal
      disease is largely unknown. We wished to determine the prevalence and clinical
      presentation of C. concisus infection in patients with enteric disease in a
      tertiary hospital. Stool specimens were routinely tested for the presence of
      Campylobacter species, by use of the filter isolation method. The medical records
      of the C. concisus-positive patients were reviewed. Of 224 Campylobacter isolates
      obtained, 110 were identified as C. concisus. Concomitant infection occurred in
      only 27% of cases. By means of protein profiling we assigned C. concisus into 2
      groups. The predominant C. concisus group 2 was the only strain to infect
      immunocompetent patients and children: 71% of the infected patients were
      immunocompromised, the majority being adults (84%). C. concisus may be a frequent
      cause of diarrhoea in immunocompromised patients. Two groups of C. concisus were
      found and these groups possibly vary in their pathogenic potential.

PMID- 12064686
TI  - Free-living amoebae promote growth and survival of Helicobacter pylori.
AB  - Transmission routes of Helicobacter pylori remain poorly understood. The finding
      of bacterial DNA in water suggests the involvement of environmental factors. Here
      we report successful co-cultivation of H. pylori with Acanthamoeba castellanii,
      which circumvents the requirement of this bacterium for precise microaerobic
      conditions and a large supply of nutrients in order to grow. H. pylori was able
      to propagate and remain viable for several weeks in the presence of amoebae under
      experimental conditions. Intact, metabolically active bacteria could be
      demonstrated in vacuoles. The putative dependence of H. pylori on free-living
      amoebae in nature could be important with respect to transmission and prevalence,
      as shown for some other pathogenic bacteria.

PMID- 12064687
TI  - Treatment of latent syphilis in HIV-infected patients with 10 d of
      benzylpenicillin G benethamine: a prospective study in Maputo, Mozambique.
AB  - Neurosyphilis has been reported in HIV-infected patients previously treated with
      penicillin G benzathine, which does not achieve treponemicidal levels in
      cerebrospinal fluid. Therapy combining benzylpenicillin G and its repository form
      benzylpenicillin G benethamine could be a potentially effective alternative
      enhanced regimen for treating latent syphilis in HIV-infected patients because
      peak serum and cerebrospinal fluid concentrations would be achieved early post
      administration by the former molecule and sustained for 24 h due to the prolonged
      half-life of the latter. In this study, 23 asymptomatic HIV and Treponema
      pallidum co-infected patients received 10 d of combined therapy (2 M IU
      intramuscular once daily) and were followed up at 3, 6 and 12 months. None
      experienced side effects or clinical symptoms. Of the 18 patients who were
      evaluated 1 y later, 8 (44.4%) exhibited serological treatment failure, defined
      as a positive serum rapid plasma reagin test. In conclusion, a 10-d regimen
      combining penicillin G and penicillin G benethamine seems to be of no benefit
      compared to currently recommended treatment.

PMID- 12064688
TI  - Diagnosis of urogenital Chlamydia trachomatis infections by home-obtained, mailed
      samples: do we need a telephone hotline for information and advice?
AB  - This study evaluates the use of dedicated telephone hotlines to provide advice to
      young individuals who were offered the chance to be tested for Chlamydia
      trachomatis by means of home-obtained samples that were mailed directly to a
      testing laboratory. In a school-based screening study, a population-based
      screening study and a partner-tracing study we established hotlines and
      registered the calls. The target groups for the 3 studies comprised 8,909, 9,000
      and 4,622 individuals and 0.1% (8/8,909), 0.7% (66/9,000) and 2.7% (124/4,622) of
      the populations, respectively took the opportunity to call anonymously to receive
      advice. The number of calls per opening hour of the hotlines varied between 0.2
      (8 calls/40 opening hours) and 0.4 (124 calls/300 opening hours). Major reasons
      for calling the hotlines included requests for more information about chlamydial
      infections, questions relating to the study and emotional concerns (e.g. problems
      relating to partner tracing, adultery or anxiety concerning infertility).
      Although only a small fraction of the target populations used the hotlines we
      conclude that there is a need for advice and counseling in connection with
      strategies involving home-obtained samples for C. trachomatis testing. The
      optimal setting for this, however, remains to be determined.

PMID- 12064689
TI  - Purification of periplasmic flagellar antigen from Borrelia microtti.
AB  - Borrelia microtti and Borrelia persica are 2 Iranian strains of Borrelia found in
      western Asia and responsible for relapsing fever. The outer surface antigens of
      Borrelia undergo variations which are responsible for the relapsing phenomenon.
      The fixed flagellar antigen is required for diagnosis as the variant antigens
      cannot be used in serological methods of diagnosis. The fixed flagellar antigen
      was purified for the first time from the Iranian strain of Borrelia microtti
      using detergent treatment and shearing in an omnimixer. Periplasmic flagella were
      extracted, as confirmed by electron microscopy. Sodium dodecyl sulphate
      polyacrylamide gel electrophoresis revealed a band corresponding to 42 kDa.
      Indirect haemagglutination kits were designed using the pure flagella and the
      complete sonicate of Borrelia and showed 98% sensitivity and 95% specificity.

PMID- 12064690
TI  - Does cross-sex transmission increase the severity of polio infection? A study of
      multiple family cases.
AB  - Previous studies have suggested that transmission of measles virus from the
      opposite sex increases the severity of infection; however, the role of gender in
      the transmission of other infections has not been examined. Multiple polio cases
      within a family usually occur simultaneously, and are therefore likely to be
      secondary to a common subclinical index case. The few clinical polio cases that
      appear much later than any other clinical case are likely to be tertiary cases.
      If cross-sex transmission increases the severity of infection then multiple polio
      cases would tend to affect the same sex, i.e. the opposite sex to that of the
      subclinical index case. In order to assess this phenomenon we identified 6345
      records of individuals hospitalized with poliomyelitis in Copenhagen between 1919
      and 1953. The severity and gender of suspected secondary and tertiary cases were
      analysed among all multiple household cases. Overall, 70% of the 133 sibling
      pairs having polio simultaneously were same-sex pairs, which differed
      significantly from the expected 52% (chi2 = 9.1; p < 0.01). Tertiary cases with
      exposure to the opposite sex were more likely to be paralytic than cases with
      exposure to the same sex [relative risk (RR) = 2.86 (95% confidence interval 1.08
      7.58)1. In families with adult polio cases, possible tertiary cases were more
      common among fathers (7/24) than among mothers (1/35) [RR = 10.21 (1.34-77.72)].
      We examined whether the excess of male polio cases was more pronounced in small
      families where the mother would play a relatively larger role in disease
      transmission and found that the male:female excess decreased with increasing
      birth order (p = 0.02) and family size (p = 0.09). The strong tendency towards
      same-sex pairs in 2-case families suggests that gender plays an important role in
      the severity of polio infection. Cross-sex transmission may increase the severity
      of polio and mothers may contribute to the higher prevalence of polio cases among
      boys.

PMID- 12064691
TI  - Neurologic morbidity after herpes simplex virus type 2 meningitis: a
      retrospective study of 40 patients.
AB  - In order to study the long-term course after herpes simplex virus type 2 (HSV-2)
      meningitis and/or myeloradiculitis the records of 40 consecutive patients were
      studied. During the year following the acute phase, verified or suspected
      neurologic recurrences were noted in nearly half of the patients: 1 or more
      episodes of recurring meningitis were noted in 8 patients; new episodes of
      myelitis or radiculitis in 3; distinct attacks of headache in 4; and diffuse
      neurologic complaints impairing daily life in 3. Recurring mucocutaneous symptoms
      were observed in 16 patients. Eleven patients experienced concurrent or separate
      episodes of recurring mucocutaneous and neurologic symptoms, 7 had neurologic
      recurrences only and 5 had only mucocutaneous recurrences. As considerable
      morbidity may result, patients with HSV-2 meningitis and/or myeloradiculitis
      should be identified by means of thorough history-taking, careful examination and
      a specific viral diagnosis in order to enable adequate advice and counseling to
      be provided and to aid decision-making regarding antiviral therapy.

PMID- 12064692
TI  - Systemic fungal infections after renal transplantation.
AB  - In a retrospective evaluation, the incidence of systemic fungal infections (SFIs)
      in 296 kidney graft recipients admitted to our center between 1986 and 1999 was
      found to be 4%. Eighteen percent of 28 recipients transplanted in India and 8% of
      12 recipients transplanted in Russia developed SFI. In contrast, SFI was
      encountered in only 2% of recipients transplanted at our center. The median time
      of diagnosis of SFI was 5 months after transplantation. The lungs and central
      nervous system were the most frequently affected sites. The most common etiologic
      agent was Aspergillus fumigatus (n = 7) but Candida spp. (n = 1), Rhizopus spp.
      (n = 1) and Cryptococcus neoformans (n = 1) were also encountered. In 2 patients,
      2 different pathogens were isolated at the same time: A. fumigatus and Rhizopus
      spp. in 1 patient and Candida spp. and A. fumigatus in another. In order to
      determine predisposing factors for SFI, patients admitted immediately before and
      after those with SFI were used as controls: long-term hospitalization, long-term
      antibiotic use and post-transplant diabetes mellitus were found to be
      predisposing factors. Eight patients were treated with antifungal drugs and a
      good response to liposomal amphotericin B therapy was obtained in 3/5. Nine
      patients (75%) with SFI died. As SFIs are associated with a high mortality rate
      in renal transplant recipients, antifungal therapy, especially with liposomal
      amphotericin B, should be started whenever fungal infection is suspected, even
      before the results of microbiologic and/or histologic examinations are known.

PMID- 12064693
TI  - The changing epidemiology of bacterial meningitis and invasive non-meningitic
      bacterial disease in scotland during the period 1983-99.
AB  - We reviewed population-based laboratory reports of invasive meningococcal,
      pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria
      monocytogenes isolates in order to examine the changing epidemiology of
      meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens
      in the 2 periods before (1983-91) and after (1992-99) routine use of H.
      influenzae type B conjugate vaccine (Hib) in Scotland. Neissieria meningitidis
      was the most common cause of meningitis, accounting for 39.2% of cases of
      meningitis in 1983-91 and 47% of cases in 1992-99, followed by H. influenzae
      (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L. monocytogenes (3.5%)
      in 1983-91 and S. pneumoniae (36.3%), H. influenzae (7.8%), GBS (6.1%) and L.
      monocytogenes (2.8%) in 1992-99. The important epidemiological features of
      meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99
      include: 1. The incidence of bacterial meningitis due to S. pneumoniae and GBS
      was stable; 2. S. pneumoniae was the predominant cause of INMD in both periods;
      3. The incidences of INMD caused by N. meningitidis, GBS and S. pneumoniae
      increased, by 27%, 55% and 56%, respectively; 4. Decreases in the incidences of
      bacterial meningitis (by 50%) and INMD (by 50%) due to L. monocytogenes were
      detected; and 5. There were dramatic reductions in the proportions of bacterial
      meningitis (by 92%) and INMD (by 56%) due to H. influenzae in vaccinated and non
      vaccinated individuals. Continued surveillance is necessary to monitor the
      disease trend, population at risk, serotype distribution and antimicrobial
      susceptibility in order to implement appropriate public health interventions
      against invasive bacterial disease.

PMID- 12064694
TI  - Septic arthritis caused by Chryseobacterium meningosepticum in an immunocompetent
      male.
AB  - This is the first report of septic arthritis of the knee caused by
      Chryseobacterium meningosepticum. The infection was associated with a penetrating
      injury to the joint. The patient was cured by flushing of the joint and
      antibiotic treatment.

PMID- 12064695
TI  - Rhodococcus equi brain abscess in an immunocompetent patient.
AB  - Rhodococcus equi brain abscesses usually occur in immunocompromised patients with
      prolonged and refractory pulmonary infections. Herein we report a case of R. equi
      brain abscess in a 67-y-old man without immunodepression. Our patient recovered
      after neurosurgical resection and prolonged antimicrobial therapy with vancomycin
      and trimethoprim-sulfamethoxazole.

PMID- 12064696
TI  - Tuberculosis of the pancreas diagnosed with needle aspiration.
AB  - Tuberculosis of the pancreas is very rare and can present with many signs and
      symptoms, including obstructive jaundice, weight loss and a mass in the head of
      the pancreas. Hence the diagnosis of pancreatic tuberculosis remains a challenge
      and a high index of suspicion is required. If a tumour is suspected then an
      ultrasound- or CT-guided fine needle aspiration should be performed. Even if the
      initial microbiological results are negative, using conventional techniques, PCR
      can yield more rapid results and avoid an unnecessary laparotomy.

PMID- 12064697
TI  - Hyper-IgM syndrome with systemic tuberculosis.
AB  - A 33-y-old man with Hyper-IgM syndrome developed a severe tuberculous disease
      complicated by pleuritis and spondylitis. An abnormally decreased CD4/CD8 ratio,
      decreased CD4 + T-cell count and depressed natural killer cell activity
      implicated a coexistent cell-mediated immunodeficiency. To our knowledge, this is
      the first detailed report of tuberculosis associated with Hyper-IgM syndrome.

PMID- 12064698
TI  - An 8-y-old boy with acute stroke and radiological signs of cerebral vasculitis
      after recent Mycoplasma pneumoniae infection.
AB  - A young boy was admitted to hospital for acute stroke. Cerebral angiography
      showed a pattern suggestive of vasculitis and a recent Mycoplasma pneumoniae
      infection was detected. The absence of microorganisms in cerebrospinal fluid, the
      pattern of vasculitis and previous reports supporting a post-infectious
      immunological mechanism for certain complications of M. pneumoniae infection
      suggest this mechanism as the cause of the stroke.

PMID- 12064699
TI  - Cryptococcal breast abscess.
AB  - A cryptococcal abscess of the breast is uncommon and may mimic a neoplastic
      lesion. We describe a patient with an isolated cryptococcal infection of the
      breast, which was treated with oral fluconazole in combination with surgical
      excision. With the exception of diabetes mellitus type II, no underlying
      predisposing illness was identified.

PMID- 12064700
TI  - Severe acute disseminated toxoplasmosis acquired by an immunocompetent patient in
      French Guiana.
AB  - Disseminated toxoplasmosis during acute infections has rarely been observed in
      immunocompetent patients. We report a case of severe acute disseminated
      toxoplasmosis acquired by an immunocompetent patient in French Guiana and review
      the literature.

PMID- 12064701
TI  - Afebrile convulsion in an adult after recombinant hepatitis B vaccination.
AB  - Vaccination against HBV is important in order to reduce the incidence of HBV
      infection. Although the HBV vaccine is among the safest of all vaccines,
      vaccination against HBV has been associated with side-effects. Herein we present
      a case of afebrile convulsion after recombinant HBV vaccination.

PMID- 12064702
TI  - Streptococcus viridans septicaemia: a comparison study in patients admitted to
      the departments of infectious diseases and haematology in a university hospital.
AB  - Infective endocarditis caused by viridans streptococci is a well-described
      disease. Streptococcus viridans is also an important etiologic agent causing
      septicaemia in neutropenic patients with haematological diseases. In this study
      we retrospectively reviewed charts from 111 patients with 121 episodes of
      viridans streptococci septicaemia during the period 1992-97 for clinical data,
      presence of endocarditis, subtype and outcome. Forty-seven episodes of S.
      viridans septicaemia were documented in 45 non-neutropenic patients treated at
      the Department of Infectious Diseases (Group A). Thirty of these episodes were
      defined as definite and 9 as possible infective endocarditis, using Duke's
      critera. Seventy-four episodes of S. viridans septicaemia were identified in 66
      patients treated at the Department of Haematology (Group B), only 1 of which
      fulfilled the criteria for possible infective endocarditis. S. sanguis was the
      most common subtype (18/47; 38%) in Group A and S. mitis was the major subtype
      (51/74; 69%) in Group B.

PMID- 12064703
TI  - Medical professionalism--a charter for all doctors.

PMID- 12064705
TI  - Return to work outcomes following accident compensation corporation work capacity
      assessment.
AB  - AIMS: To determine the proportion of Accident Compensation Corporation (ACC)
      claimants who have returned to fulltime work after ceasing to receive ACC weekly
      compensation following Work Capacity Assessment (WCAP). To assess what factors
      impact on return to work. To assess whether ACC's research findings into return
      to work outcomes WCAP are valid. METHODS: A structured questionnaire telephone
      follow-up survey was conducted with ACC claimants seen for WCAP. RESULTS: 43% of
      those exited from ACC weekly compensation after WCAP were currently working
      fulltime. Claimants who had exited ACC after WCAP were significantly more likely
      to be working than those remaining on ACC. Claimants over 40 years of age were
      significantly less likely to be working. Gender, race, length of time since
      injury, and retraining made no difference to return to work. 80% of claimants
      felt that the WCAP process was unfair. CONCLUSION: Nearly half of those claimants
      certified as being unfit for work but now exited from ACC via WCAP were working
      fulltime. This may indicate that ACC's rehabilitation is successful, or that
      claimants tend to remain on ACC for economic rather than injury reasons, or that
      WCAP results in claimants returning to physically unsuitable work putting them at
      risk of further injury. ACC's research finding, that 79% of claimants were
      working after WCAP does not appear to be valid.

PMID- 12064704
TI  - Comparison of cancer mortality and incidence in New Zealand and Australia.
AB  - AIMS: To compare cancer mortality and incidence data from New Zealand and
      Australia, in order to gauge the potential for reducing deaths from cancer in New
      Zealand. METHODS: For 1996 and 1997, numbers of deaths from cancer, numbers of
      new cases, and population data were stratified in 5-year age-groups. Numbers
      observed in New Zealand were compared with numbers expected from Australian
      rates. Age-standardized mortality and incidence rates for each sex were analysed.
      RESULTS: New Zealanders of both sexes experienced more deaths from cancer than
      expected in every age group. If Australian rates had applied, there would have
      been 215 fewer cancer deaths per year in New Zealand males, and 616 fewer in
      females. The largest differences related to breast cancer and lung cancer in
      women, and colorectal cancer in both sexes. The overall incidence of cancer was
      higher in New Zealand, but mortality/incidence ratios were also higher for many
      sites--suggesting that survival after treatment has been poorer in New Zealand
      than in Australia. CONCLUSIONS: Considerable scope exists for reducing cancer
      mortality in New Zealand. For a national cancer control strategy, it will be
      essential to clarify reasons for the high incidence of cancer and to study
      survival following treatment.

PMID- 12064706
TI  - Co-morbidity and health outcomes in three Auckland hospitals.
AB  - AIMS: To establish the burden of co-morbid disease using the Charlson Index among
      hospital inpatients and its relationship to key health outcomes. METHODS: An
      initial screen was carried out on 1575 medical records selected by systematic
      list sample from admissions for 1995 in three public hospitals in the Auckland
      region. In the course of the administration of the instrument, screeners were
      required to record the occurrence of co-morbid disease using the Charlson Index.
      RESULTS: A third of patients had co-morbid disease, of which chronic pulmonary
      disease and congestive heart failure were the most frequently recorded. While the
      Charlson Index was associated with age of patient, length of stay, inpatient
      mortality, and adverse event status, the simple presence or absence of co
      morbidity was as an effective predictor as the extended index. Co-morbidity was
      more likely to be recorded for Maori, for patients from deprived areas, and for
      circulatory or respiratory diagnoses. Specific co-morbid conditions were
      predictive of health outcomes. CONCLUSIONS: Levels of co-morbid disease
      established for patients using the Charlson Index in three Auckland public
      hospitals are similar to those recorded internationally. Co-morbidity is
      predictive of key health outcomes that are of clinical and managerial
      significance. Controlling for co-morbidity will be important in making
      comparisons of the quality of care.

PMID- 12064707
TI  - Home intravenous antimicrobial service--twelve months experience in Christchurch.
AB  - AIM: To review the clinical practice and complications of the home intravenous
      antimicrobial service at Christchurch Hospital after twelve months of full
      operation. METHODS: Clinical and microbiological diagnoses, antimicrobial
      therapy, and complications of home intravenous antimicrobial therapy were entered
      prospectively on an Excel data base. RESULTS: Of the 153 patients, 113 (74%)
      suffered from skin, soft tissue or bone and joint disease. A bacteriological
      diagnosis was made in 108 patients (71%). 119 patients were treated with the
      narrow spectrum agents--penicillin 20 (13%), flucloxacillin 55 (36%) and
      cephazolin 44 (29%). Ceftriaxone was used for treatment in fifteen (10%)
      patients. Peripherally inserted central catheters (PICC's) were used in 129
      patients, midlines fifteen, peripheral angiocaths in eight, and a Portacath in
      one. An elastomeric infusion device was used in 80 patients and an infusion pump
      in 34. Complications developed in 31 (20%) patients including three infections
      and one jugular vein thrombosis. Fifteen patients (10%) were readmitted within
      one month of discharge. CONCLUSIONS: The home intravenous therapy programme
      successfully used first line narrow spectrum agents initiated in hospital with
      avoidance of unnecessary broad spectrum agents. Complication rates were
      acceptable and likely to improve with experience in patient selection and
      provision of support services.

PMID- 12064708
TI  - Public knowledge and attitudes regarding smoking and smoking cessation
      treatments.
AB  - AIMS: To investigate current public knowledge and attitudes to tobacco smoking
      and smoking cessation treatments. METHOD: A telephone survey of 250 individuals
      randomly selected from the Christchurch Electoral Roll and assigned into one of
      three groups: current, ex and life-time never smokers. RESULTS: Significantly
      more current than ex-smokers cited habit as a major reason for continuing to
      smoke and a greater number reported using nicotine transdermal patches during a
      cessation attempt. Fewer ever smokers than never smokers stated health as a
      likely major motivation for cessation by smokers and believed doctors' advice and
      illness of a significant other highly influenced quit attempts. 55.7% of
      respondents believed nicotine patches to be the most effective smoking cessation
      method followed by 'cold turkey' (49.4%) and hypnotherapy (33.9%). While the
      majority of participants supported banning tobacco advertising (69.6%), banning
      tobacco sponsorship (59.6%), lower insurance rates for non-smokers (89.1%) and
      fully subsidised smoking cessation programmes (71.9%), significant differences
      were detected between groups regarding attitudes to tobacco control initiatives.
      CONCLUSIONS: This sample were relatively ill informed regarding smoking practices
      in New Zealand and unaware of useful information to aid cessation. While evidence
      emerged to support current smokers being slightly better informed regarding
      proven strategies for cessation than ex-smokers, few current smokers were aware
      of efficacious interventions for smoking cessation.

PMID- 12064710
TI  - The new Journal.

PMID- 12064709
TI  - Two cases of adrenal suppression following a Chinese herbal remedy: a cause for
      concern?

PMID- 12064711
TI  - Demise of the printed NZ Med J. Where the Journal fits in my life.

PMID- 12064713
TI  - Conduct unbecoming.

PMID- 12064714
TI  - How did we let it happen?

PMID- 12064715
TI  - Pyridine alkaloids from a Parthenium hybrid.
AB  - Two pyridine alkaloids were isolated from the derubberized resin of the hybrid
      Parthenium argentatum x P tomentosa. These alkaloids are (+/-)-N-[4-(1
      aminoethyl) phenyl]-4-[3-methylbutenylidine]-1,4-dihydropyridine (guayulamine A)
      and (+/-)-N-[4-(1-aminoethyl) phenyl]-4-[4-methylpentenylidine]-1, 4
      dihydropyridine (guayulamine B). The structures were established by one- and two
      dimensional NMR spectroscopy and mass spectrometry.

PMID- 12064716
TI  - Flavonol glycosides from Cadaba glandulosa.
AB  - A new flavonol triglycoside, rhamnocitrin-3-O-neohesperoside-4'-O-glucoside was
      isolated from the ethanol extract of Cadaba glandulosa together with two known
      diglycosides rhamnocitrin-3-O-neohesperoside and rhamnetin-3-neohesperoside.
      Characterization of the three compounds was achieved by various spectroscopic
      methods.

PMID- 12064717
TI  - Neolignan glucosides from Phlomis chimerae Boiss.
AB  - From the aerial parts of the plant Phlomis chimerae, a new neolignan glucoside, (
      )-4-O-methyldihydrodehydrodiconiferyl alcohol-9'-O-beta-D-glucopyranoside (1) was
      characterized along with the known neolignan glucosides, (-)-4-O
      methyldehydrodiconiferyl alcohol-9'-O-beta-D-glucopyranoside (= longifloroside A)
      (2) and (-)-dihydrodehydrodiconiferyl alcohol-9-O-beta-D-glucopyranoside (3). The
      structure of the new compound was established on the basis of spectroscopic
      evidence.

PMID- 12064718
TI  - Iridoid patterns in Galium L. and some phylogenetic considerations.
AB  - From 19 species of Galium, members of 6 European sections of the genus, 24
      compounds were isolated, namely 16 iridoid glucosides, 2 secoiridoid glucosides
      and 6 triterpene saponins (the later found only in G. rivale (Sibth. & Sm.
      Griseb.) The iridoid content was analyzed by thin layer chromatography -
      densitometry. An effort was made to clarify interspecies relationships, based on
      the obtained results and previous data. Generally, a nearly uniform iridoid
      pattern in the studied species was observed. Nevertheless, some distinctions gave
      reason the following chemical characters to be treated as taxonomic markers:
      iridoids, secogalioside (characteristic of G. mollugo group), iridoids V1 and V2
      (G. humifusum Bieb. and G. verum L.), 6-acetylscandoside (G. incurvum group and
      G. verum) and the triterpene saponins, rivalioside A and rivalioside C
      (characteristic of G. rivale). The studied species regarding to the iridoids
      could be attributed to three lines of evolutionary differentiation. One line is
      leading to the differentiation of G. rivale. It contains specific triterpenoids
      as well as iridoid acids, which show parallel development of both glyceraldehyde
      3-phosphate/pyruvate and mevalonate biosynthetic routes in this species. A second
      line includes G. mollugo and G. incurvum species groups and the species G.
      humifusum and G. verum. Variety of iridoid esters, hydroxy and carboxy
      derivatives of iridoids and secoiridoids characterised this line. Third line
      comprises the remaining studied species, members of different sections and
      species groups. They posses a nearly identical iridoid pattern, which suggests a
      convergent evolution regarding to the iridoids.

PMID- 12064719
TI  - Paeonicluside, a new salicylic glycoside from the Greek endemic species Paeonia
      clusii.
AB  - A new glycoside of salicylic aldehyde, paeonicluside, was isolated from the roots
      of the Greek endemic species Paeonia clusii subsp. clusii and identified as alpha
      L-arabinopyranosyl-(1-->6)-O-beta-D-glucopyranoside of salicylic aldehyde (1). In
      addition, one characteristic monoterpene and two monoterpene glycosides were
      identified as paeoniflorigenone, paeoniflorin and benzoyl paeoniflorin,
      respectively. The structure of 1 was elucidated on the basis of its spectroscopic
      data and chemical correlation. It is the first time that a derivative of
      salicylic aldehyde is isolated from the well-studied Paeonia genus.

PMID- 12064720
TI  - GC-MS of Crinum latifolium L. alkaloids.
AB  - A GC-MS analysis of underivatized alkaloids from leaves of Crinum latifolium was
      performed. From the identified 15 alkaloids, 9 were found for the first time in
      this plant. Almost all alkaloids belonged to the crinane type. Substantial
      changes in the methylation and oxidation pattern of the alkaloids at and after
      flowering were observed.

PMID- 12064721
TI  - Alkaloid profile of leaves and seeds of Lupinus hintonii C. P. Smith.
AB  - L. hintonii C. P. Smith grows in the Central Highland forests of Mexico at
      altitudes between 2800 m to 3200 m above see level. Members of the genus Lupinus
      produce quinolizidine alkaloids as main chemical defensive compounds against
      herbivores. Surprisingly alkaloid profiles are rather constant within this
      species, while substantial variation was found when compared to morphologically
      closely related other taxa. As part of a phytochemical project on Mexican wild
      lupins, we report on the alkaloid profiles of seeds and leaves of L. hintonii. 19
      alkaloids could be identified by capillary GLC-MS. Six major alkaloids occurred
      in leaves and seeds: 13-hydroxylupanine (28% and 45% respectively),
      tetrahydrorhombifoline (31% and 23% respectively), angustifoline (2% and 4%
      respectively), lupanine (7% and 5% respectively), 13alpha-tigloyloxylupanine (19%
      and 5% respectively) and 4alpha-angeloyl-3beta-hydroxylupanine (9% and 2%). This
      chemical pattern resembles that of the North American lupin L. floribundus.

PMID- 12064722
TI  - Distribution of hydrolysable tannins in the foliage of Finnish birch species.
AB  - On the basis of qualitative and quantitative analysis with liquid chromatography-
      electrospray ionisation mass spectrometry, the foliage of dwarf birch (Betula
      nana L.), silver birch (B. pendula Roth) and mountain birch (B. pubescens ssp.
      czerepanovii (Orlova) Hamet-Ahti) were found, for the first time, to contain the
      same individual HTs that were described earlier for white birch (B. pubescens
      Ehrh.). In addition, one previously unidentified ellagitannin was preliminarily
      identified from the leaves of white and mountain birches, being totally absent
      from the foliage of the other two species. There were large variations in the
      contents of HTs between species. Seasonal variation affected significantly the
      contents of some individual HTs within species, and these changes were mainly in
      accordance with the biosynthetic pathway of HTs. All species converted
      galloylglucoses (GGs) into ellagitannins (ETs), dwarf birch being the only one
      that's efficient ET synthesis resulted in seasonally increased contents of ETs
      and thereof total HTs as well. The presence of insoluble ETs as well as the
      absence of insoluble GGs was confirmed in all four birch species for the first
      time. Furthermore, the amounts of insoluble ETs per one birch leaf were found to
      accumulate during the growing season. These findings complemented our knowledge
      of the biosynthetic pathway of birch leaf HTs: from soluble GGs via soluble ETs
      into insoluble ETs. The possible role of HTs in the herbivore defence of these
      species is discussed.

PMID- 12064724
TI  - Studies on the biosynthesis of striatal-type diterpenoids and the biological
      activity of herical.
AB  - Feeding experiments with specifically 13C-labeled glucose disclosed that the
      diterpenoid part of the striatals/striatins is formed via the mevalonate pathway,
      whereas the pentose moiety originates either via glucuronic acid (70%) or the
      pentose phosphate cycle (30%). Application of radioactively labeled herical to
      cultures of Hericium ramosum demonstrates the pivotal role of this cyathane
      xyloside in striatal biosynthesis. Herical inhibits a large spectrum of fungi and
      bacteria and shows cytotoxic and hemolytic properties.

PMID- 12064725
TI  - Cytotoxic, hypoglycemic activity and phytochemical analysis of Rubus imperialis
      (Rosaceae).
AB  - Rubus imperialis, Artemia salina, 3-O-methylellagic-4'-O-alpha-rhamnose Acid
      Screening of different extracts, fractions and compounds from Rubus imperialis
      Chum. Schl. (Rosaceae) has been conduced using the brine shrimp microwell
      cytotoxicity assay. Three parts of the plant (methanolic extract from leaves,
      roots and stems), three fractions from roots (hexane, ethyl acetate and butanol)
      and three isolated compounds (niga-ichigoside F1, 23-hydroxytormentic acid,
      ellagic acid derivative) were tested. The most promising material (LC50 <1000
      microg/ml) were the methanolic extract and ethyl acetate fraction from roots.
      However, there was little correlation observed in the degree of toxicities
      observed between the isolated compounds. On the other hand, the cytotoxicity and
      in vivo assays confirmed the hypoglycemic activity of methanolic extract and
      validated the Brazilian popular use of R. imperialis as an antidiabetic agent.

PMID- 12064723
TI  - The himanimides, new bioactive compounds from Serpula himantoides (Fr.) Karst.
AB  - In a screening of basidiomycete cultures from Chile for the production of
      antibiotics we identified a Serpula himantoides strain as a producer of
      metabolites inhibiting the growth of bacteria and fungi. Bioactivity guided
      purification resulted in the isolation of four new antibiotics. Their structures
      were elucidated by spectroscopic methods. All four compounds are succinimide and
      maleimide derivatives, of which two are N-hydroxylated.

PMID- 12064726
TI  - In vitro antiplasmodial investigation of medicinal plants from El Salvador.
AB  - In vitro antiplasmodial activities of extracts from Albizia saman, Fabaceae,
      Calea tenuifolia (C. zacatechichi), Asteraceae, Hymenaea courbaril, Fabaceae,
      Jatropha curcas, Euphorbiaceae, Momordica charantia, Cucurbitaceae, and Moringa
      oleifera, Moringaceae were evaluated. From the lipophilic extract of C tenuifolia
      five active flavones were obtained. 4',5-Dihydroxy-7-methoxyflavone [genkwanin]
      and 5-hydroxy-4',7-dimethoxyflavone [apigenin 4',7-dimethylether] exhibited the
      strongest antiplasmodial activity against a chloroquine-sensitive strain (poW)
      and a chloroquine-resistant strain (Dd2) of Plasmodium falciparum [IC50 values:
      17.1-28.5 microM). Furthermore octadeca-9,12-dienoic acid [linoleic acid] [IC50]
      values of 21.8 microM (poW) and 31.1 microM (Dd2)] and octadeca-9,12,15-trienoic
      acid (alpha-linolenic acid) were isolated.

PMID- 12064727
TI  - Antiplasmodial activities of sesquiterpene lactones from Eupatorium semialatum.
AB  - Eupatorium semialatum, Plasmodium falciparum, Sesquiterpene Lactones Eupatorium
      semialatum is a member of the Asteraceae, which occurs in Guatemala. Previously,
      we reported the occurrence of sesquiterpene lactones of the eudesmanolide type as
      main constituents in the leaves. This paper deals with the isolation and
      identification of the first guaianolide found in E. semialatum. Since this plant
      is used against malaria and other diseases in the Guatemalan folk medicine, the
      main sesquiterpene lactones were tested for their activities against Plasmodium
      falciparum in vitro.

PMID- 12064728
TI  - Chemical composition and in-vitro antimicrobial activity of the essential oils of
      three Greek Achillea species.
AB  - The chemical composition of the essential oils of Achillea holosericea, Achillea
      taygetea, Achillea fraasii was determined by GC/MS analysis. Among the ninety
      five assayed constituents, camphor, borneol and 1,8-cineol were found to be the
      major components. The in-vitro antimicrobial activity of these essential oils was
      evaluated against six bacteria indicating that the first is totally inactive,
      while the other two possess moderate to strong activities mainly against the Gram
      negative strains. The essential oil of A. fraasii was also active against the
      tested pathogenic fungi.

PMID- 12064729
TI  - Antifungal garcinia acid esters from the fruits of Garcinia atroviridis.
AB  - Two new garcinia acid derivatives, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2
      hydroxy-3-propanolide and 1',1"-dibutyl methyl hydroxycitrate, were isolated from
      the fruits of Garcinia atroviridis guided by TLC bioautography against the fungus
      Cladosporium herbarum. The structures of these compounds were established by
      spectral analysis. The former compound represents a unique beta-lactone structure
      and the latter compound is most likely an artefact of garcinia acid (=
      hydroxycitric acid). Both compounds showed selective antifungal activity
      comparable to that of cycloheximide (MID: 0.5 microg/spot) only against C
      herbarum at the MIDs of 0.4 and 0.8 microg/spot but were inactive against
      bacteria (Bacillus subtilis, methicillin-resistant Staphylococcus aureus,
      Pseudomonas aeruginosa and Escherichia coli), other fungi (Alternaria sp.,
      Fusarium moniliforme and Aspergillus ochraceous) including the yeast Candida
      albicans.

PMID- 12064730
TI  - Partitioning of carbohydrates and biomass of needles in Scots pine canopy.
AB  - The study was aimed at the quantitative evaluation of the temporal and spatial
      partitioning of non-structural carbohydrates and needle biomass in a canopy of
      Scots pine (Pinus sylvestris L.) growing in a Myrtillus site type forest stand
      (predominant in Estonia). The tree canopy was divided into ten equal layers and
      the material for the spatial partitioning of the investigated characteristics was
      sampled from all layers. Our findings revealed a significant variation in
      morphology and in the partitioning of carbohydrates in needles in different
      layers of the canopy. The study of the temporal dynamics of carbohydrates showed
      that starch content in needles started to increase in early spring before
      budbreak, which was accompanied by a decline in soluble carbohydrates. In
      October, the starch content of needles was low, but the concentration of soluble
      sugars started to increase attaining a maximum in winter. Regression analysis
      indicated that before budbreak, the partitioning of soluble sugars in different
      canopy layers was relatively weakly correlated with the height of the layer;
      however, a strong correlation was observed for starch. In autumn, when the growth
      of trees stopped and daily temperatures decreased, the allocation of soluble
      sugars was correlated with the height of the canopy layer.

PMID- 12064732
TI  - Inability of Agrobacterium tumefaciens ribosomes to translate in vivo mRNAs
      containing non-Shine-Dalgarno translational initiators.
AB  - Numerous data accumulated during the last decade have shown that the Shine
      Dalgarno (SD) sequence is not a unique initiator of translation for Escherichia
      coli. Several other sequences, mostly of viral origin, have demonstrated their
      capability of either enhancing or initiating translation in vivo. A phage T7 gene
      10 sequence, called "epsilon" (epsilon), has shown its high enhancing activity on
      translation in both Escherichia coli and Agrobacterium tumefaciens cells. In this
      study the epsilon, together with three other nucleotide sequences derived from
      the 5' non-translated regions of tobacco mosaic virus (TMV), papaya mosaic virus
      (PMV) and clover yellow mosaic virus (CYMV) RNAs are tested for translation
      initiation activity in A. tumefaciens cells. The obtained results indicate that
      none of them was capable of initiating translation in vivo of chloramphenicol
      acetyltransferase (CAT) mRNA. To determine whether their inactivity was related
      with structural differences in the ribosomal protein S1, the rpsA gene (coding
      for S1 protein in E. coli) was co-expressed in A. tumefaciens together with the
      cat gene placed under the translational control of the above sequences. Our
      results showed that the rpsA gene product did not make any of the four viral
      enhancers active in A. tumefaciens cells. The inability of A. tumefaciens
      ribosomes to translate mRNAs devoid of SD sequences indicates for a substantial
      difference in the ribosome structure of the two Gram negative bacteria E. coli
      and A. tumefaciens.

PMID- 12064731
TI  - Biotransformation of (-)-a-pinene by Botrytis cinerea.
AB  - (-)-alpha-Pinene (1), a major constituent of many aromatic plants was
      biotransformed by the plant pathogenic fungus, Botrytis cinerea to afford three
      new metabolites, characterized as 3beta-hydroxy-(-)-beta-pinene (10%) (3), 9
      hydroxy-(-)-a-pinene (12%) (4), 4beta-hydroxy-(-)-alpha-pinene-6-one (16%) (5) by
      physical and spectroscopic methods. A known metabolite verbenone (2) was also
      obtained.

PMID- 12064733
TI  - Superoxide dismutase during glucose repression of Hansenula polymorpha CBS 4732.
AB  - Hansenula polymorpha CBS 4732 was studied during cultivation on methanol and
      different glucose concentrations. Activities of Cu/Zn and Mn superoxide
      dismutase, catalase and methanol oxidase were investigated. During cultivation on
      methanol, increased superoxide dismutase and catalase activities and an induced
      methanol oxidase were achieved. Transfer of a methanol grown culture to medium
      with a high glucose concentration caused growth inhibition, low consumption of
      carbon, nitrogen and phosphate substrates, methanol oxidase inactivation as well
      as decrease of catalase activity (21.8 +/- 0.61 deltaE240 x min(-1) x mg protein(
      1)). At the same time, a high value for superoxide dismutase enzyme was found
      (42.9 +/- 0.98 U x mg protein(-1), 25% of which was represented by Mn superoxide
      dismutase and 75% - by the Cu/Zn type). During derepression methanol oxidase was
      negligible (0.005 +/- 0.0001 U x mg protein(-1)), catalase tended to be the same
      as in the repressed culture, while superoxide dismutase activity increased
      considerably (63.67 +/- 1.72 U x mg protein(-1), 69% belonging to the Cu/Zn
      containing enzyme). Apparently, the cycle of growth inhibition and reactivation
      of Hansenula polymorpha CBS 4732 cells is strongly connected with the activity of
      the enzyme superoxide dismutase.

PMID- 12064734
TI  - Copper (II) accumulation and superoxide dismutase activity during growth of
      Aspergillus niger B-77.
AB  - The influence of copper (II) ions on the growth, accumulation properties and
      superoxide dismutase (SOD) activity of a growing culture of Aspergillus niger B
      77 were studied. Microbial growth, the level of copper (II) accumulation and SOD
      activity depended on the initial copper (II) concentration. Aspergillus niger is
      able to accumulate large amounts of copper (II) from the nutrient medium with 200
      mg x l(-1) copper (II) ions without loosing its biological activities. Addition
      of copper (II) ions increased the SOD activity in the growing cell cultures. The
      changes in enzyme activity induced by heavy metal ions might be used as an
      indicator of intracellular oxy-intermediate generation in a cell culture growing
      under stress conditions.

PMID- 12064735
TI  - Nicotinamide and structurally related compounds show halting activity against
      zoospores of the phytopathogenic fungus Aphanomyces cochlioides.
AB  - In a survey of plant secondary metabolites regulating the behavior of
      phytopathogenic Aphanomyces cochlioides zoospores, we found that leaf extracts of
      Amaranthus gangeticus and cotyledon extracts of pea (Pisum sativum) remarkably
      halted the motility of zoospores. Bioassay-directed fractionation of A.
      gangeticus and pea constituents revealed that the halting activity was dependent
      on a single chemical factor (halting factor). The active principle was identified
      as nicotinamide (1) by comparing its biological activity and spectroscopic
      properties with those of the authentic compound. Nicotinamide (1) showed potent
      halting activity toward the zoospores of A. cochlioides and A. euteiches, but it
      exhibited very less activity against other Oomycetes, Pythium aphanidermatum and
      Phytophthora infestans zoospores. Interestingly, the zoospores halted by
      nicotinamide (1) encysted within 10-15 min and then the resulting cystospores
      regenerated zoospores instead of germination. Nicotinamide (1) and related
      compounds were subjected to the halting activity bioassay to elucidate the
      structure-activity relationships. These bioassays revealed that part structures
      of (A) the aromatic ring containing at least one nitrogen atom, (B) carbonyl-like
      group adjacent to the aromatic ring and (C) hydrogen atoms on the amide group are
      responsible for the strong activity. So far, this is the first report of halting
      activity of nicotinamide (1) against fungal zoospores.

PMID- 12064736
TI  - Interaction of folk medicinal plant extracts with human alpha2-adrenoceptor
      subtypes.
AB  - Forty-two extracts of folk medicinal plant organs from Pakistan were tested in
      competition binding assays for their interaction with the specific ligand
      recognition sites on the human alpha2-adrenoceptor subtypes alpha2A, alpha2B and
      alpha2C Strong binding of the extracts (40 mg/ml) from Acacia nilotica (L.)
      Delile leaves (88-98% displacement of radiolabel) and Peganum harmala seeds (89
      96% displacement) on three subtypes prompted us to extract these plant materials
      with 40% and 80% methanol, ethanol, and acetone. The extraction results indicated
      an absence of alpha2-adrenoceptor binding activity in the stalk of A. nilotica
      and A. tortils, whereas the leaves of both plants contained activity. The
      extracts of A. nilotica leaves showed a slight, but consistent, preference for
      the alpha2C-adrenoceptor, whereas the leaves of A. tortils were slightly more
      active on the alpha2B subtype. The extract of P. harmala stalks was less active
      than that of its seeds. The binding activities of A. nilotica leaves and P.
      harmala seeds were mainly concentrated in the water and 30% methanol fractions
      and further sub-fractions. In a functional activity assay, the active fractions
      inhibited epinephrine-stimulated 35S-GTPyS binding, thus indicating a
      predominantly antagonistic nature of the compounds with alpha2-adrenoceptor
      affinity in these fractions. Among the known major alkaloids of P. harmala
      (demissidine, harmaline, harmine, 6-methoxyharmalan, and norharmane), only 6
      methoxyharmalan showed moderate affinity (dissociation constant (Ki) of 530 +/-
      40 nm for alpha2A subtype). This study is a first systematic attempt towards the
      discovery of potential drug candidates from these plant materials for treating
      alpha2-adrenoceptor related diseases.

PMID- 12064737
TI  - Effect of diesel fuel pollution on the lipid composition of some wide-spread
      Black Sea algae and invertebrates.
AB  - Two green algae (Ulva rigida and Cladophora coelothrix), the mussel Mytilus
      galloprovincialis and the snail Rapana thomasiana from the Bulgarian Black Sea
      shore have been treated with diesel fuel (100mg l(-1)) in an aquarium with sea
      water for three days. The lipids and their fatty acid changes have been examined.
      Significant changes have been observed mainly in the polar lipids and in the
      saturation of the fatty acids. These changes appeared to be bigger in the
      evolutionary less advanced species from both groups of marine organisms--algae
      and invertebrates (Ulva rigida and Mytilus galloprovincialis respectively). The
      data obtained could be used for a biomonitoring of the pollution.

PMID- 12064738
TI  - Antioxidative properties of pyrrolidinium and piperidinium salts.
AB  - Two series of pyrrolidinium (PYA-n) and piperidinium (PPPA-n) bromides with
      incorporated antioxidant function were synthesized. Both have hydrocarbon chains
      with odd number of the carbon atoms (n) ranging between 7 and 15. Pig
      erythrocytes (RBC) were used to study antioxidant activity of these compounds.
      They were incorporated into RBC membranes in sublytic (micromolar) concentrations
      and RBC were then subjected to UV radiation. It was found that all the salts used
      protected erythrocyte membranes against oxidation of membrane lipids. This
      protection increased with hydrocarbon chain length. Such effect may be the result
      of an incorporation of particular compounds to different depths into the lipid
      phase of RBC membrane depending on their chain length. Such possibility was
      checked by studies on fluidity changes induced by the compounds studied in ghost
      membranes by fluorimetric measurements. The measurements showed that
      pyrrolidinium bromides were slightly more effective in a protection of
      erythrocytes than the corresponding piperidinium ones. The possible reason of
      such behaviour may be the difference in lipophilicity between piperidine and
      pyrrolidine rings.

PMID- 12064740
TI  - Biosurfactant production by a new Pseudomonas putida strain.
AB  - Observation of both tensio-active and emulsifying activities indicated that
      biosurfactants were produced by the newly isolated and promising strain
      Pseudomonas putida 21BN. The biosurfactants were identified as rhamnolipids, the
      amphiphilic surface-active glycolipids usually secreted by Pseudomonas spp. Their
      production was observed when the strain was grown on soluble substrates, such as
      glucose or on poorly soluble substrates, such as hexadecane, reaching values of
      1.2 g l(-1). When grown on hexadecane as the sole carbon source the biosurfactant
      lowered the surface tension of the medium to 29 mN m(-1) and formed stable and
      compact emulsions with emulsifying activity of 69%.

PMID- 12064739
TI  - A novel binding assay for metabotropic glutamate receptors using [3H] L
      quisqualic acid and recombinant receptors.
AB  - We established a methodology to analyze radioligand binding to the recombinant
      type la metabotropic glutamate receptor (mGluRla). A full-length cDNA encoding
      mGluR1a, which was isolated from a lambda gt 11 cDNA library of human cerebellar
      origin, was expressed in a baculovirus/Sf9 insect cell system. Membrane fractions
      with recombinant receptor expression were analyzed for the binding of [3H]L
      quisqualic acid (L-QA), which is known to be a potent agonist of mGluRla.
      Efficient binding of the radioligand to the human receptor was observed in a
      saturable manner, giving an apparent Kd= 0.091 microM. [3H]L-QA bound to the
      human mGluR1a was displaced by known ligands such as L-QA, L-Glu, t-ACPD ((+/-)-1
      aminocyclopentane-trans-1,3-dicarboxylic acid) with IC50s = 0.056, 0.97 and 4.0
      microM, respectively. MCPG (alpha-methyl-4-carboxyphenylglycine) displaced the
      radioligand binding with lower potency. Using this binding protocol, we then
      evaluated the ligand ability of synthetic dipeptides. Among peptides tested, only
      Glu-containing dipeptides inhibited the radioligand binding, e.g. IC50 of L-Met-L
      Glu was 4.3 microM. When phosphatidyl inositol turnover was assayed in mGluR1a
      expressing CHO cells, L-Met-L-Glu was partially agonistic. We further expanded
      this [3H]L-QA binding protocol to type 5a mGluR, another member of group I
      mGluRs, as well as to AMPA receptor, a member of ionotropic glutamate receptors,
      since L-QA is also known to be a potent ligand for these receptors. Data shown
      here will provide a novel system not only to search for ligands for the glutamate
      receptors, but also to biochemically analyze the interaction modes between
      glutamate receptors and their ligands.

PMID- 12064741
TI  - Damage to subcellular structures evoked by lipid peroxidation.
AB  - Subcellular Structures, Lipid Peroxidation, Free Radical Scavengers The influence
      of lipid peroxidation (LP) on the rate of disruption of rat liver and kidney
      subcellular structures was studied under two experimental conditions. Damage to
      cell organelles was found only when peroxidation process carried out into large
      granule fraction suspensions. Exogenous thiobarbituric acid positive products
      were noneffective as membrane labilizers. Age, organ and cell organelle-linked
      differences in the response towards LP produced damage were observed. Rat liver
      peroxisomes showed higher stability than those of kidney with respect to injury
      induced by peroxidation process. In addition, in rat kidney and neonatal rat
      liver samples the lysosomes were found to be more sensitive than mitochondria to
      the damaging effect of this process. Thiourea, an inhibitor of diene conjugate
      formation as well as manitol and ethanol known as hydroxyl radical scavengers
      were tested as terminators of LP and as membrane protectors. Effectiveness was
      demonstrated only for thiourea.

PMID- 12064742
TI  - Antigen levels of urokinase type plasminogen activator and its inhibitors in
      primary breast cancer.
AB  - Primary Breast Cancer, Urokinase-Type Plasminogen Activator, Inhibitors The aim
      of the study was to monitor urokinase plasminogen activator antigen
      concentrations and its type 1 (PAI-1) and type 2 (PAI-2) inhibitors in
      histologically defined forms of primary breast cancer and a comparison with these
      antigens levels in normal tissue. Another goal was a search for a relationship/or
      its lack/between the occurrence of the new generation markers of neoplastic
      disease and a presence/or absence/of lymph node metastases. U-PA, PAI-1 and PAI-2
      antigen levels were determined by ELISA tests in protein extracts of breast
      cancer tissues. Among the studied breast tumors 32 specimens were ductal
      carcinomas, 15 specimens were lobular carcinomas and the remaining 13 were other
      rare histological forms. In comparison to the obtained values of u-PA antigen
      levels in normal tissue, the values in neoplastic tissues were elevated several
      times: 11-fold, 6-fold and 15-fold in ductal c., lobular c. and other rare
      neoplasms. The values of PAI-1 antigen levels were about 20-fold higher for all
      studied, histologically defined primary breast cancers. The greatest differences
      of PAI-2 antigen levels growth was observed in histologically defined primary
      breast cancer forms. It was augmented 10-fold, 40-fold and 20-fold, respectively,
      for ductal carcinoma, lobular carcinoma and rare forms of neoplasms. In various
      forms of invasive breast cancer and those without lymph node metastases the
      content of u-PA, PAI-1 and PAI-2 were also significantly elevated. Among the new
      generation of independent markers of the neoplastic process, PAI-2 seems to be
      the most reliable marker for the identification of primary breast cancer. The
      goal of the present study was to evaluate a possible combined prognostic value of
      the three major components of the u-PA system (u-PA, PAI-1 and PAI-2) in patients
      with defined histopathological forms of primary breast cancer.

PMID- 12064743
TI  - Polyisoprenylated benzophenones in cuban propolis; biological activity of
      nemorosone.
AB  - The Copey tree (Clusia rosea) has a large distribution in Cuba and its floral
      resin is a rich source of polyisoprenylated benzophenones. To determine the
      presence of these natural products, we carried out a study by HPLC of 21 propolis
      samples produced by honey bees (Apis mellifera) from different provinces of Cuba.
      Nemorosone resulted to be the most abundant polyisoprenylated benzophenone and
      the mixture of xanthochymol and guttiferone E was also observed, but in minor
      proportion. We studied the biological activity of the pure natural product
      nemorosone and its methyl derivatives. We found that nemorosone has cytotoxic
      activity against epitheloid carcinoma (HeLa), epidermoid carcinoma (Hep-2),
      prostate cancer (PC-3) and central nervous system cancer (U251). It also
      exhibited antioxidant capacity. Methylated nemorosone exhibited less biological
      activity than the natural product.

PMID- 12064744
TI  - Prophylactic effect of aqueous propolis extract against acute experimental
      hepatotoxicity in vivo.
AB  - Propolis has been extensively used in folk medicine for the management of a wide
      spectrum of disorders. In a previous study, we demonstrated the protective effect
      of the aqueous propolis extract (APE) against the injurious effects of carbon
      tetrachloride (CCl4) on hepatocytes in vitro. The present investigation was
      carried out to show whether the hepatoprotective effect of the extract could also
      be manifested in vivo. Rats were given APE orally for 14 consecutive days, before
      being subjected to a single intraperitoneal injection of CCl4. One day after the
      CCl4 injection, the animals were sacrificed, hepatocytes were isolated and liver
      homogenates were prepared for the assessment of liver injury. In isolated
      hepatocytes, APE afforded protection against CCl4-induced injury as manifested by
      a decrease in the leakage of the cytosolic enzyme lactate dehydrogenase (LDH),
      decreased generation of lipid peroxide and maintenance of cellular reduced
      glutathione (GSH) content. In principle, similar findings were observed in liver
      homogenates. The present findings show that APE has in vivo hepatoprotective
      potential which could be attributed at least in part to the maintenance of
      cellular GSH content. The latter effect seems to play an important role in
      conserving the integrity of biomembranes as it was associated with a decrease in
      lipid peroxidation and reduced leakage of cytosolic LDH.

PMID- 12064745
TI  - Egyptian propolis: 2. Chemical composition, antiviral and antimicrobial
      activities of East Nile Delta propolis.
AB  - Three propolis samples from East Nile Delta, Egypt were collected. Propolis
      samples were investigated by GC/MS,103 compounds were identified, 20 being new
      for propolis. Dakahlia propolis was a typical poplar propolis but it contained
      two new caffeate esters and two new triterpenoids. Ismailia propolis was
      characterized by the presence of new triterpenic acid methyl esters and it did
      not contain any aromatic acids, esters and flavonoids. Sharkia propolis was
      characterized by the presence of caffeate esters only, some di- and
      triterpenoids. The antiviral (Infectious Bursal Disease Virus and Reo-Virus) and
      antimicrobial (Staphylococcus aureus; Escherichia coli and Candida albicans)
      activities of propolis samples were investigated. Dakahlia propolis showed the
      highest antiviral activity against Infectious Bursal Disease Virus (IBDV) and the
      highest antibacterial activity against Escherichia coli and the highest
      antifungal activity against Candida albicans. While Ismailia propolis had the
      highest antiviral activity against Reo-virus. Sharkia propolis showed the highest
      antibacterial activity against Staphylococcus aureus and moderate antiviral
      activity against infectious bursal disease virus and reovirus.

PMID- 12064746
TI  - Egyptian propolis: 3. Antioxidant, antimicrobial activities and chemical
      composition of propolis from reclaimed lands.
AB  - The free radical scavenging effect of two propolis samples collected from
      reclaimed land, Egypt as well as of vitamin C and caffeic acid in 1,1-diphenyl-2
      picrylhydrazyl (DPPH) free radical system was determined. The antimicrobial
      (Staphylococcus aureus; Escherichia coli and Candida albicans) activity was also
      investigated. The results of the free radical scavenging effect of El-Saff and
      Ismailia propolis showed a concentration-dependent activity. The antioxidant
      activity was varied according to the examined material. It was obvious that
      caffeic acid and vitamin C showed the highest activity if compared with the
      propolis samples. El- Saff propolis had a higher antioxidant activity than
      Ismailia propolis, it showed a higher antibacterial activity against
      Staphylococcus aureus and a higher anti-fungal activity against Candida albicans.
      While the Ismailia propolis had a higher antibacterial activity against
      Escherichia coli, than El-Saff propolis. The chemical composition of propolis
      samples was investigated by GC/MS, where 75 compounds were identified, 22 being
      new for propolis. The Ismailia propolis was characterized by the presence of a
      highly significant amount of aromatic acid esters (47.3%) and triterpenoids
      (17.3%), while El-Saff propolis contained 3% and 1.9% respectively. The new
      esters belonged to 4-methoxyhydrocinnamic acid, hydroferulic acid and ferulic
      acid. El-Saff propolis had a very high significant amount (27%) of 2,6-bis
      (pentanyloxy)-4-pentanylphenethanol, which is also a new compound for propolis.

PMID- 12064748
TI  - Correlation between HSP90 induction kinetics in murine leukemia cells and the
      amount of cisplatin over a wide range of cytostatic concentrations.
AB  - The induction of HSP90 in murine erythroleukemia cells, clone F4 N, by cisplatin
      (DDP) was examined using indirect immunofluorescence and avidin-biotin technique,
      and compared with cisplatin cytotoxicity. A reverse dependence of HSP90 induction
      time was found on a wide range of cisplatin concentrations (0.5-10 microM), which
      proved to be cytostatic up to 48 h of continuous treatment. Thus, the observed
      induction pattern of HSP90 in F4 N cells strictly correlated with their high
      tolerance toward DDP. This indicates that HSP90 might be responsible, at least in
      part, for cisplatin resistance of F4 N cells.

PMID- 12064747
TI  - Isomeric triterpenoids from Peritassa campestris.
AB  - An investigation of the MeOH extract from the roots of Peritassa campestris
      (Hippocrateaceae) afforded two isomeric seco-A-ring quinonemethide triterpenoids,
      campestrine-I (1) and -II (2). This appears to be the first report of a C26,-type
      triterpene carbon skeleton from the Celastraceae or Hippocrateaceae families. The
      structures were elucidated on the basis of spectral data, particularly HMQC, HMBC
      and NOE experiments.

PMID- 12064749
TI  - Proceedings of the Seattle Symposium on Cancer Outcomes Research.

PMID- 12064750
TI  - A framework for outcomes research in cancer: response to Carolyn Clancy.

PMID- 12064751
TI  - The outcomes of the cancer outcomes research symposium: a commentary.

PMID- 12064752
TI  - What outcomes matter to patients: a physician-researcher point of view.
AB  - BACKGROUND: During the last quarter of the 20th century, it became feasible to
      measure and take into account the patient's subjective preferences for health
      states and various outcomes. This has become increasingly relevant in the
      treatment of cancer, where patients are confronted with a life-threatening
      illness and may have varied treatment choices and outcomes. OBJECTIVES: To
      provide a framework for examining the outcomes that matter to patients from a
      clinician-researcher perspective. Considerations include the heterogeneity of the
      cancer patient population, the influence of the setting of care on patient
      outcomes, the range of outcomes that are often considered by patients and
      researchers, and possible study designs that should be considered to measure
      outcomes that are important to patients. The outcomes that matter to patients can
      broadly be classified into disease-focused and patient-focused outcomes.
      CONCLUSIONS: There are many challenges in the measurement of patient-focused
      outcomes, including consensus on what are the most important outcomes and the
      methods for their measurement. In addition, it is often difficult to integrate
      disease-focused and patient-focused outcomes in the same setting, particularly
      for use in clinical decision making. We need to develop some key strategies to
      enhance patient outcomes including (1) emphasis on evidence-based treatments
      whenever possible, as the best way of improving disease-focused outcomes; (2) the
      inclusion of patient preferences when different treatment alternatives provide
      equivalent disease-focused outcomes; and (3) the provision of adequate time for
      communication about disease-focused and patient-focused outcomes, with emphasis
      on the training of clinicians to facilitate these discussions.

PMID- 12064753
TI  - When the physician-researcher gets cancer: understanding cancer, its treatment,
      and quality of life from the patient's perspective.
AB  - The authors, both medical researchers, describe their personal experiences with
      cancer, its treatment, and its effects on their lives. They discuss the "eight
      Ds" that represent their concerns as they navigated this permanent disruption in
      their lives: diagnosis, dying, discomfort, disability, drug and other treatment
      effects, dependency, doubt, and death. They also discuss the beneficial effects
      that cancer has had on their lives and end with suggestions for clinicians and
      outcomes researchers who seek to assess and improve quality of life among persons
      with cancer.

PMID- 12064754
TI  - What outcomes matter to patients: a surgeon's perspective.

PMID- 12064755
TI  - The Outcomes of Cancer Outcomes Research: focusing on the National Cancer
      Institute's quality-of-care initiative.
AB  - BACKGROUND: To assess the impact of outcomes research, the Agency for Healthcare
      Policy and Research has proposed a four-level typology that successively
      distinguishes between research that (1) adds to the knowledge base only, (2)
      affects practice policies, (3) influences the delivery of care, and (4) leads to
      changes in health outcomes. The agency has concluded that outcomes research to
      date has made substantial contributions at level 1, but has had little impact at
      levels 2 to 4. OBJECTIVE: To describe the National Cancer Institute's emerging
      agenda in cancer outcomes research, focusing on how it has been shaped early on
      to support the institute's quality of care initiative and noting whether each new
      project represents outcomes research at level 1, 2, 3, or 4. RESULTS: Cancer
      outcomes research describes, interprets, and predicts the impact of various
      influences, especially (but not exclusively) interventions on endpoints that
      matter to decision makers. The institute's projects to improve the scientific
      quality of final endpoint measures, strengthen the methodologic and empirical
      basis for quality of care analysis, and enhance the application of health-related
      quality-of-life measures in clinical trials represent level 1 applications of
      outcomes research. Collaborative projects with federal agencies to translate
      evidence into practice and a new public and private effort to identify core
      measures of cancer quality represent level 2 and level 3 outcomes research.
      CONCLUSION: The stage has been set for carrying out a balanced portfolio of level
      1 to 3 outcomes research projects in cancer, with the ultimate (level 4) aim of
      improving cancer-related health outcomes.

PMID- 12064756
TI  - A taxonomy of the uses of health-related quality-of-life instruments in cancer
      care and the clinical meaningfulness of the results.
AB  - OBJECTIVES: To propose a taxonomy of psychometrically based, health-related
      quality-of-life instruments related to three levels of decision-making of health
      care: the macro, meso and micro levels. The choice of appropriate health-related
      quality-of-life instruments for each level of desired decision making in various
      clinical settings is illustrated. A secondary objective was to describe solutions
      for some of the difficulties inherent in the interpretation of the results of
      health-related quality-of-life assessment. DESIGN: The three main levels of
      clinical decision making are listed and the instruments used most frequently in
      cancer clinical trials are reviewed from the medical literature. PROPOSALS:
      Generic and utility-based instruments are likely to be the most valuable at the
      macro level of decision making, whereas condition-specific, disease-specific, and
      situation-specific instruments are most useful for decision making at the meso
      and micro levels. A determination of the proportions of patients who have reached
      a meaningful change in health-related quality-of-life scores (eg, > or =10 for
      scales of 1-100) over a standard period is a rational approach to interpreting
      the significance of changes in scores. CONCLUSIONS: Awareness of the level of
      decision making that is involved in the clinical assessment of health-related
      quality of life can be helpful in choosing instruments that are appropriate for
      various clinical settings. Some of the difficulties in interpreting the meaning
      of changes in health-related quality-of-life scores can be overcome by comparing
      the proportions of patients who have achieved a preset magnitude of change.

PMID- 12064757
TI  - Individual differences in quality-of-life treatment response.
AB  - BACKGROUND: Individual differences in treatment responses to health-related
      quality-of-life interventions arise ubiquitously and prominently in clinical
      trials. These differences do not reflect error, but instead represent patterns of
      response that vary reliably across patients. Individual differences complement
      and qualify the information conveyed by average health-related quality-of-life
      effects for treatment arms. If clinicians and patients are to use health-related
      quality-of-life findings from clinical trials to make treatment decisions, they
      must have information about the extent and nature of such individual variation.
      The relatively small effect sizes of health-related quality-of-life outcomes in
      clinical trials offer a weak basis for generalizing results to new persons, and
      patients routinely anticipate likely treatment benefits for themselves that
      exceed these small effects. A focus on individual differences in treatment
      response can promote more realistic appreciation of expected benefit and
      uncertainty. A pharmacogenetic example shows how individual differences in drug
      metabolism can directly affect health-related quality-of-life treatment outcomes
      such as pain and physical functioning. MEASURES: The authors suggest how
      graphical displays can summarize individual responses and provide a context for
      interpreting the size and generality of the average treatment. Mixed-effects
      modeling subsumes average treatment differences and individual differences in a
      unified statistical analysis. Analysis of health-related quality-of-life data
      from an advanced colorectal cancer trial illustrates this approach. Objective
      statistical criteria indicate that, for this example, individual differences
      dominate the treatment difference. CONCLUSIONS: The authors suggest that
      presentation of the spectrum of individual responses and associated prediction
      intervals can convey clinically meaningful information regarding the impact of a
      treatment on health-related quality of life.

PMID- 12064758
TI  - Seattle Symposium on Cancer Research Outcomes: commentary on the papers by
      Donaldson and Moinpour and by Osoba.

PMID- 12064759
TI  - The potential clinical value of quality-of-life information response to Martin.

PMID- 12064760
TI  - Measuring costs: administrative claims data, clinical trials, and beyond.
AB  - BACKGROUND: Accurate estimation of medical care costs raises a host of issues,
      both practical and methodological. OBJECTIVES: This article reviews methods for
      estimating the long-term medical care costs associated with a cancer diagnosis.
      METHODS: The authors consider data from administrative claims databases and
      describe the analytic challenges posed by these increasingly common resources.
      They present a number of statistical methods that are valid under censoring and
      describe methods for estimating mean costs and controlling for covariates. In
      addition, the authors compare two different approaches for estimating the cancer
      related costs; namely, the portion of the long-term costs that may be attributed
      to the disease. Examples from economic studies of breast and colorectal cancer
      are presented. RESULTS: In an analysis of data on colorectal cancer costs from
      the SEER-Medicare database, the two methods used to estimate expected long-term
      costs (one model based, one not model-based) yielded similar results. However, in
      calculating expected cancer-related costs, a method that included future medical
      costs among controls yielded quite different results from the method that did not
      include these future costs. CONCLUSIONS: Statistical methods for analyzing long
      term medical costs under censoring are available and appropriate in many
      applications where total or disease-related costs are of interest. Several of
      these approaches are nonparametric and therefore may be expected to be robust
      against the non-standard features that are often encountered when analyzing
      medical cost data.

PMID- 12064762
TI  - Developing measures of mammography performance.

PMID- 12064761
TI  - Developing a reliable, valid, and feasible plan for quality-of-care measurement
      for cancer: how should we measure?
AB  - BACKGROUND: Recent changes in the US health care delivery system have raised
      expectations that the medical marketplace will compete on quality and cost of
      care. This effort will require a systematic evaluation of the measurement of
      quality of care as it applies to cancer and other critical conditions.
      OBJECTIVES: To articulate the components of the design of quality-of-care
      measurement systems that must be considered and optimally manipulated to generate
      feasible, reliable, and valid data pertinent to patients with cancer. RESEARCH
      DESIGN: A synthesis of information obtained from literature reviews and
      experience. MEASURES: Four key areas of design that influence quality-of-care
      measurement scores are discussed: case identification, data source, data
      collection strategies, and the quality of the care-measurement model. RESULTS:
      Challenges associated with these design and measurement strategies are defined
      and discussed. CONCLUSIONS: Policy analyses vary as a function of measurement
      domains. The design of a quality-of-care measurement system should consider trade
      offs between validity and burden by considering the intricate relations between
      domains of measurement.

PMID- 12064763
TI  - Some thoughts on outcomes research, quality improvement, and performance
      measurement.
AB  - Outcomes research, quality improvement, and performance measurement are important
      activities in the cancer research community. They are, indeed, closely related
      activities because indicators of quality and performance can logically be
      regarded as the outcomes of interest in outcomes research. Considerable progress
      has been made in the past decade in broadening the definition and strengthening
      the measurement of the important outcomes of health care in general, and cancer
      care specifically. The real value of studying outcomes, according to the
      Donabedian paradigm, lies in understanding their relation to the structure and
      processes (eg, the health care) that have produced them, because it is these
      latter factors which we can control. Therefore, the methods that we have
      available to us by which we can infer this relation of causality become very
      important. Because the systems that we study in health care research are usually
      complex, we will need to invest more of our resources in the future in the
      development of methods of inference beyond what we have available now if we are
      to realize the full potential of health outcomes research. This presents a unique
      opportunity for leadership by the cancer outcomes research program.

PMID- 12064764
TI  - Is outcomes research on cancer ready for prime time?
AB  - Contemporary treatment of patients with cancer has been challenged by the same
      influences that have stimulated broad interest among stakeholders in assessing
      the outcomes or "results" of medical care. These interrelated external forces
      include growing awareness of practice variations, increased recognition of the
      patient's central role in decision making, acknowledgment that treatment
      decisions for situations where cure is not possible require explicit metrics to
      assess trade-offs between length and quality of life, strong interest in cost
      containment, and broad public concern that efforts to rationalize spending may
      have led to decreases in quality of care. Clinical and health services
      researchers interested in cancer diagnosis and treatment have striven to address
      these issues and have been in the forefront of efforts to develop and use valid
      measures of health-related quality of life. However, the current challenges to
      the field of outcomes research are equally applicable to those applying its tools
      and methods to the study of cancer: lack of standardization of outcomes measures,
      limited evidence that assessing outcomes of care is followed by improved outcomes
      in practice, and development of a research infrastructure that links the products
      of outcomes research with informed, shared decision making in routine practice.
      The purpose of this article is to provide a brief overview of lessons learned
      from the first decade of outcomes research sponsored by the Agency for Healthcare
      Research and Quality that will inform suggested directions for future directions
      for cancer outcomes research.

PMID- 12064765
TI  - Cadmium ions modulate GABA induced currents in molluscan neurons.
AB  - The effect of Cd2+, as one of the most widespread toxic environmental pollutants,
      was studied on gamma-aminobutyric acid (GABA) evoked responses of identified
      neurons in the central nervous system of the pond snail, LYmnaea stagnalis L.
      (Gastropoda). In the experiments, the modulation of the action of GABA both on
      neuronal activity (current clamp recording) and on the a GABA activated membrane
      Cl- current (voltage clamp studies) has been shown. It was found that: 1. GABA
      could evoked three different various types of response in GABA sensitive neurons:
      i) hyperpolarization with strong inhibition of ongoing spike activity, ii) short
      depolarization with an increase of spike the activity, iii) biphasic respone with
      a short excitation followed by a more prolonged long inhibition. 2. In low-Cl-
      solution the inhibitory action of GABA was reduced or eliminated, but the
      excitatory one was not or only moderately affected. 3. CdCl2 inhibited the GABA
      evoked hyperpolarization, but left intact or only slightly reduced the excitation
      evoked by GABA. 4. The inward Cl- current evoked by GABA at a -75 mV holding
      potential was slightly augmented in the presence of I micromol/l Cd2+, but was
      reduced or blocked at higher cadmium concentrations. The effect of Cd2+ was
      concentration and time dependent. 5. Parallel with reducing the GABA evoked
      current, cadmium increased both the time to peak and the half inactivation time
      of the current. 6. CdCl2 alone, in 50 micromol/l concentration, induced a 1-2 nA
      inward current. The blocking effect of cadmium on GABA activated inhibitory
      processes can be an important component of the neuro-toxic effects of this heavy
      metal ion.

PMID- 12064766
TI  - Ultrastructure of neuromuscular contacts in the embryonic pond snail Lymnaea
      stagnalis L.
AB  - Ultrastructural characteristics of muscle fibers and neuromuscular contacts were
      investigated during two stages of embryogenesis of the pulmonate snail Lymnaea
      stagnalis. The first muscle cells appear as early as during metamorphosis (50-55%
      of embryonic development), whereas previously, in the trochophore/veliger stages
      (25-45%), muscular elements cannot be detected at all. The first muscle fibers
      contain large amounts of free numbers, a well-developed rER system and only a few
      irregularly arranged contractile elements. The nucleus is densely packed with
      heterochromatine material. At 75% adult-like postmetamorphic stage, the frequency
      of muscle fibers increases significantly, but, bundles of muscle fibers cannot
      yet be observed. Furthermore the muscle cells are characterized by large numbers
      of free ribosomes and numerous rER elements. Fine axon bundles and single axon
      processes, both accompanied by glial elements, can already be found at this time.
      Axon varicosities with different vesicle and/or granule contents form membrane
      contacts with muscle fibers, but without revealing membrane specialization on the
      pre- or postsynaptic side. The late development of the muscle system and
      neuromuscular contacts during Lymnaea embryogenesis correlates well with the
      maturation of different forms of behavior of adult, free-living life, and also
      with the peripheral appearance of chemically identified components of the
      embryonic nervous system of central origin.

PMID- 12064768
TI  - Position and size of the axon hillock in various groups of neurons.
AB  - The origin of the axon was studied in Golgi-Kopsch impregnated specimens prepared
      from the spinal cord and brain of adult rats. Five types of neurons were sampled:
      large ventral horn neurons, neurons in the intermediate zone and ventral horn of
      the spinal cord, antenna-type neurons in the spinal dorsal horn, neurons in the
      thalamus, and neurons in the hypothalamus. The axon originated from the
      perikaryon in 76% of the large ventral horn neurons and in 64% of the neurons in
      the thalamus. In contrast, the axon emerged from one of the dendrites in 75% of
      the neurons in the intermediate zone and the ventral horn of the spinal cord and
      in 68% of the neurons in the hypothalamus. In the case of the antenna-type
      neurons in the spinal dorsal horn, the axon often originated from one of the
      dendrites, but never from a dorsally oriented dendrite. The mean distance of the
      axon hillock of dendritic origin was the longest in the neurons in the
      intermediate zone and the ventral horn of the spinal cord. The size of the axon
      hillock was proportional to the size of the perikaryon. The impregnated portion
      of the axon was longest in the large ventral horn neurons.

PMID- 12064767
TI  - Electrophysiological evidence for push-pull interactions in the inner retina of
      turtle.
AB  - The responses of the inner retinal neurons of turtle to light spots of sizes were
      studied in an attempt to reveal characteristics that may reflect possible
      interactions of the neural circuits underlying the center and surround responses.
      For the ON-OFF cells, the responses were also analyzed to observe whether
      interference or augmentation of these responses occur. The intracellular
      recordings revealed several such interactions, observed either in the form of
      altered spike activity or as changes in the transiency of the light responses.
      The ON-responding amacrine cell presented in this study became more sustained,
      while for the ON-OFF amacrine cells larger light spots tended to make the
      responses more transient and both the ON and OFF components became more
      pronounced. The spiking activity of the OFF-type ganglion cell shifted in
      relation to the light stimulus and the number of spikes observed upon
      presentation of larger spots increased. We suggest that the surround circuits
      activated by increasing light spots may substantially influence and reorganize
      not only the overall center-surround balance, but also the center response of the
      cells. Although it cannot be excluded that intrinsic membrane properties also
      influence these processes to some extent, it is more likely that lateral
      inhibition and disinhibitory mechanisms play the leading role in this process.

PMID- 12064769
TI  - Age-related mitochondrial damage in the B-type cells of the rat trigeminal
      ganglia.
AB  - Aging is associated with signs of sensory impairment and neurological symptoms.
      Advancing age is characterized by increased thresholds of thermal, tactile and
      vibratory sensations. One important cause of the sensory disturbances has been
      stated to be the loss of neurons. Decreases have been observed in the number of
      peripheral nerve fibers and in the number of neurons in the spinal ganglia of
      rats. In the present study, the cytoplasmic organelles of the neurons of the
      trigeminal ganglia were examined in young and senescent rats in order to reveal
      the cause of cell loss during aging. Mitochondrial alterations, swelling and loss
      of internal cristae were observed from 23 week of age in the B-type neurons of
      the trigeminal ganglia. Other cytoplasmic elements were intact. Mitochondrial
      damage was never seen in A-type neurons and satellite glial cells. It was
      concluded that the ultrastructural changes in the mitochondria of the B-type
      cells may contribute to the nervous disturbances that occur in senescent
      individuals. The diminution of mitochondrial damage and the protection of B-type
      neurons through the use of nerve growth factors may prevent the sensory
      impairment late in life.

PMID- 12064770
TI  - Branching-pattern analysis of the dendritic arborization in the thalamic nuclei
      of the rat brain.
AB  - We investigated the dendritic patterns of rapid Golgi-impregnated, highly similar
      multipolar neurons from two functionally different thalamic regions of the rat
      brain: two dorsal nuclei (the nucleus laterodorsalis thalami, pars dorsomedialis
      and the nucleus laterodorsalis thalami, pars ventrolateralis), and two ventral
      nuclei (the nucleus ventrolateralis thalami and the nucleus ventromedialis
      thalami). The analysis involved conventional morphometric parameters (height and
      size) and a new parameter derived from graph theory, the relative imbalance (RI),
      derived from the branching patterns of the dendrites, which permits quantitative
      characterization of the dendritic arborization of a neuron. On this basis,
      neurons can be grouped into three fundamentally different types: type A, or
      highly-polarized (imbalanced) neurons (RI values close to 1); type B, or medium
      polarized neurons (RI values around 0.5); and type C, or balanced neurons with
      low polarization (RI values close to 0). The orientations of the dendritic arbor,
      and thus the receptive fields, of the dorsal and ventral thalamic neurons, were
      mutually perpendicular. The H and S values indicated that the neurons in the
      dorsal and ventral thalamic nuclei differed significantly. However, their RI
      values demonstrated that they were similar neurons of type B. Our data reveal
      that 1 ) the dendritic arbor cannot be reliably characterized purely on the basis
      of height and size, and 2) RI is a valuable morphometric parameter that
      identifies the true nature of the dendritic arborization.

PMID- 12064771
TI  - Morphological study of organotypic cerebellar cultures.
AB  - Organotypic cerebellar cultures from 8-days-old (P8) mouse pups were studied
      following 11 days of in vitro (I IDIV) culturing. The cerebellar
      cytoarchitectonic structure was maintained in most parasagittal cerebellar
      cortical slice cultures (also containing the deep cerebellar nuclei). The two
      main extrinsic excitatory inputs (the climbing and the mossy fibers) seem to be
      replaced by other axonal types: in the molecular layer mostly by parallel fibers
      (for climbing fibers) and in the granular layer by intrinsic mossy fiber
      collaterals of local excitatory interneurons, the unipolar brush cells. However,
      in a few organotypic cultures, which (although preserving the trilaminar
      cerebellar cortical structure) were "granuloprival" but also contained some of
      the deep cerebellar nuclei, the participation of extracortical axons from the
      deep cerebellar nuclei in the replacement of the missing afferents is suggested.

PMID- 12064772
TI  - Calretinin-containing interneurons innervate both principal cells and
      interneurons in the CA1 region of the human hippocampus.
AB  - Hippocampal interneurons consist of functionally diverse cell types, most of them
      target the dendrites or perisomatic region of pyramidal cells with a few
      exceptions, like the calretinin-containing cells in the rat: they selectively
      innervate other interneurons. However, no electron microscopic data are available
      about the synaptic connections of calretinin-immunoreactive neurons in the human
      hippocampus. We aimed to provide these data to establish whether interneuron
      selective interneurons indeed represent an essential feature of hippocampal
      circuits across distant species. Two types of calretinin-immunostained terminals
      were found in the CA1 region: one of them presumably derived from the thalamic
      reuniens nucleus, and established asymmetric synapses on dendrites and spines.
      The other type originating from local interneurons formed symmetric synapses on
      both pyramidal and interneuron dendrites. Distribution of postsynaptic targets
      showed that 26.8% of the targets were CR-positive interneuron dendrites, and
      25.2% proved to be proximal pyramidal dendrites. CR-negative interneuron
      dendrites were also contacted (12.4%). Small caliber postsynaptic dendrites were
      not classified (28%). Somata were rarely contacted (7.6%). The present data
      suggest that calretinin-positive boutons do show a preference for other
      interneurons, but a considerable proportion of the targets are pyramidal cells.
      We propose that interneuron-selective inhibitory cells exist in the human Ammon's
      horn, and boutons innervating pyramidal cells derive from another cell type that
      might not exist in rodents.

PMID- 12064773
TI  - Modulation of backward pattern masking by focal visual attention.
AB  - The effect of focal visual attention on backward pattern masking was investigated
      using an orientation discrimination task. The results show that attention reduces
      primarily the effect of interruption masking, the later component of pattern
      masking, which occurs when the delay between the target and mask onset is about
      50-150 ms. The strongest spatial cueing effect, i.e. the strongest reduction of
      the orientation discrimination threshold due to focal attention, was observed at
      intermediate (approximately 100 ms) target-to-mask stimulus onset asynchrony
      (SOA). There was a weak effect of cueing at shorter SOAs, and no or a very weak
      attentional effect was present at longer target-to-mask SOAs, where the pattern
      masking effect is absent. The dynamics of attentional modulation of backward
      pattern masking correlates closely with the dynamics of the attentional
      modulation of neuronal responses in the early visual cortex.

PMID- 12064774
TI  - Nonsynaptic noradrenaline release in neuro-immune responses.
AB  - Evidence has recently been obtained that the branches of the autonomic nervous
      system, mainly, the sympathetic [25], regulate cytokine production. Not only the
      primary (thymus, bone marrow) and secondary (spleen, tonsils, and lymph nodes)
      lymphoid organs, but also many other tissues are involved in immune responses and
      are heavily influenced by noradrenaline (NA) derived from varicose axon terminals
      of the sympathetic nervous system [25, 100]. Besides NA released from nonsynaptic
      varicosities of noradrenergic terminals [92], circulating catecholamines
      (adrenaline, dopamine, NA) are also able to influence immune responses, the
      production of pro- and anti-inflammatory cytokines by different immune cells. The
      sympathetic nervous system (catecholamines) and the hypothalamic-pituitary
      adrenal (HPA) axis (cortisol) are the major integrative and regulatory components
      of different immune responses. In our laboratory convincing evidence has been
      obtained that NA released non-synaptically [90, 92] from sympathetic axon
      terminals and enhanced in concentration in the close proximity of immune cells is
      able to inhibit production of proinflammatory (TNF-alpha, IFN-gamma, IL-12, IL-1)
      and increase antiinflammatory cytokines (IL-10) in response to LPS [25, 91],
      indicating a fine-tuning control of the production of TNF-alpha and other
      cytokines by sympathetic innervation under stressful conditions. This effects are
      mediated via beta2-adrenoceptors expressed on immune cells and coupled to cAMP
      levels.

PMID- 12064775
TI  - Ultrastructure of neuropeptide-Y immunoreactive elements in the superior
      colliculus of cat.
AB  - Whereas the presence of neuropeptide-Y (NPY) in the superior colliculus (SC) has
      been established, its participation in the ultrastructural organisation of the
      neuronal networks in the SC has not been studied. Accordingly, in the present
      paper light and electron microscopic NPY immunohistochemical studies were
      performed on the SC of cat. NPY fibres were found to be present predominantly in
      the superficial grey layer (SGL) of the SC, though a few small NPY cells were
      found in both the deeper and the upper layers. Ultrastructural observations
      revealed that the NPY nerve endings establish almost exclusively axo-dendritic
      synaptic contacts in the SGL of the SC. Thus, the presumably inhibitory impact of
      the NPY terminals is exerted through the dendrites of the SGL neurons, and not
      directly to the retinal axons, as thought previously.

PMID- 12064776
TI  - How to make a neuroscientist?

PMID- 12064777
TI  - Somato-dendritic synapses in the nucleus reticularis thalami of the rat.
AB  - In the reticular nucleus of the rat thalamus, about 30% of the synapses are
      brought about by the perikarya of parvalbumin-immunopositive neurons, which
      establish somato-dendritic synapses with large dendrites of nerve cells of
      specific thalamic nuclei. Although the parvalbumin-immunopositive presynaptic
      structures bear resemblance to goblet-like or calyciform axonal endings, electron
      microscopic immunocytochemistry and in situ hybridization revealed that these
      structures are parts of the perikaryal cytoplasm studded with synaptic vesicles.
      In about 15% of the somato-dendritic synapses, axons are seen to be in synaptic
      contact with the parvalbumin-immunoreactive perikaryon. Double
      immunohistochemical staining revealed that the parvalbumin immunoreactive
      presynaptic perikarya and dendrites contained GABA. It is assumed that the
      peculiar somato-dendritic synaptic complexes subserve the goal of filtration of
      impulses arriving at the reticular nucleus from various thalamic nuclei, thus
      processing them for further sampling.

PMID- 12064778
TI  - Reorganization of the GABAergic system following brain extirpation in the
      earthworm (Eisenia fetida, Annelida, Oligochaeta).
AB  - The reorganization of the GABAergic system was studied by means of
      immunohistochemistry after the symmetrical and asymmetrical (unilateral)
      extirpation of the brain of the annelid Eisenia fetida. GABA-immunoreactive
      neurons were first observed in the wound tissue on the 3rd postoperative day.
      Thereafter the number of labelled cells gradually increased, and by postoperative
      days 76-80 all GABA-immunoreactive cells (approx. 140 neurons) could be found in
      their final positions in the symmetrically regenerated brain. After asymmetrical
      brain extirpation, nearly all cells (70-75) could be detected in the regenerating
      hemisphere by postoperative days 50-56. In the early stages of the asymmetrical
      regeneration of the brain, more GABAergic cells were concentrated dorsally and
      laterally in the preganglion than during the symmetrical type of regeneration. In
      both types of regeneration, the immunoreactive neurons in the regenerated brain
      originated in part from undifferentiated neuroblasts situated in different parts
      of the body, and in part from dividing neurons localized mainly in the pharyngeal
      nerve plexus. Both exogenous GABA and picrotoxin, applied during the early stages
      (days 10- 12) of brain regeneration, inhibited the development of the wound
      tissue and the migration of the neuroblasts and the enteric neurons. At the same
      time, exogenous GABA application accelerated the proliferation of the pharyngeal
      neurons. No effect on the process of regeneration could be demonstrated when
      exogenous GABA and picrotoxin were given together.

PMID- 12064779
TI  - Autoradiographic evaluation of [11C]vinpocetine binding in the human postmortem
      brain.
AB  - The main objective ofthe study was to evaluate with autoradiographic technique
      whether or not [11C]vinpocetine, a compound widely used in the prevention and
      treatment of cerebrovascular diseases (Cavinton, Gedeon Richter Ltd., Budapest),
      binds to specific sites in the human brain in post mortem human brain sections.
      Binding was assessed under four conditions: the incubation was performed using
      Tris-HCl buffer with or without the addition of salts (0.1% (weight/vol) ascorbic
      acid, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2 and 1 mM MgCl2), with or without the
      addition of excess (10 microM) unlabelled vinpocetine. Measurements on digitized
      autoradiograms indicated that [11C]vinpocetine labelled all grey matter areas in
      the human brain to a similar extent and no significantly heterogeneous binding
      could be demonstrated among cortical or subcortical regions. The addition of
      excess unlabelled vinpocetine lowered the binding slightly in all regions.
      Although these results indicate that [11C]vinpocetine does not bind to human
      brain transmitter receptors or transporters with a high affinity (Ki < 10 nM), it
      cannot be ruled out that the compound binds to receptors and/or transporters with
      lower affinity.

PMID- 12064780
TI  - Transneuronal induction of the highly sialylated isoform of the neural cell
      adhesion molecule following nerve injury.
AB  - The polysialylated, embryonic form of the neuronal cell adhesion molecule (PSA
      NCAM) is known to participate in a whole series of synaptic rearrangements even
      in adult animals. The possible role of this molecule in neuroplastic changes of
      the adult rat somatosensory cortex induced by unilateral transection of the
      infraorbital branch of the trigeminal nerve was studied with PSA-NCAM
      immunostaining at light microscopic level. Two- and three-month-old CFY albino
      rats were sacrificied on days 1, 4, 6, 14 and 21 following operation and PSA-NCAM
      immunoreaction was examined at three levels of the vibrissa-cortex neuraxis,
      namely, in the principal nucleus of the trigeminal nerve, in the ventral
      posteromedial nucleus of the thalamus and in the somatosensory cortex. The lower
      levels of the neuraxis remained free of PSA-NCAM labeling, similarly to control,
      intact animals. However, a large number of scattered small neurons became PSA
      NCAM immunoreactive in layers IV-VI on both ipsi- and contralateral sides of the
      somatosensory cortex from day 6 onwards, suggesting a possible transynaptic
      regulation of NCAM sialylation state.

PMID- 12064781
TI  - Ascending and descending projections of the lateral vestibular nucleus in the
      rat.
AB  - The tracer neurobiotin was injected into the lateral vestibular nucleus in rat
      and the efferent fiber connections of the nucleus were studied. The labeled
      fibers reached the diencephalon rostrally and the sacral segments of the spinal
      cord caudally. In the diencephalon, the ventral posteromedial and the gustatory
      nuclei received the most numerous labeled fibers. In the mesencephalon, the
      inferior colliculus, the interstitial nucleus of Cajal, the nucleus of
      Darkschewitch, the periaqueductal gray matter and the red nucleus received large
      numbers of labeled fibers. In the rhombencephalon, commissural and internuclear
      connections originated from the lateral vestibular nucleus to all other
      vestibular nuclei. The medioventral (motor) part of the reticular formation was
      richly supplied, whereas fewer fibers were seen in the lateral (vegetative) part.
      In the spinal cord, the descending fibers were densely packed in the anterior
      funiculus and in the ventral part of the lateral funiculus. Collaterals invaded
      the entire gray matter from lamina IX up to lamina III; the fibers and terminals
      were most numerous in laminae VII and VIII. Collateral projections were rich in
      the cervical and lumbosacral segments, whereas they were relatively poor in the
      thoracic segments of the spinal cord. It was concluded that the fiber projection
      in the rostral direction was primarily aimed at sensory-motor centers; in the
      rhombencephalon and spinal cord, fibers projected onto structures subserving
      various motor functions.

PMID- 12064782
TI  - Peripheral nerve lesion-induced uptake and transport of choleragenoid by
      capsaicin-sensitive c-fibre spinal ganglion neurons.
AB  - In the present experiments the effect of systemic capsaicin treatment on the
      retrograde labelling of sensory ganglion cells was studied following the
      injection of choleratoxin B subunit-horseradish peroxidase conjugate (CTX-HRP)
      into intact and chronically transected peripheral nerves. In the control rats CTX
      HRP injected into intact sciatic nerves labelled medium and large neurons with a
      mean cross-sectional area of 1,041 +/- 39 gm2. However, after injection of the
      conjugate into chronically transected sciatic nerves of the control rats, many
      small cells were also labelled, shifting the mean cross-sectional area of the
      labelled cells to 632 +/- 118 microm2. Capsaicin pretreatment per se induced a
      moderate but significant decrease in the mean cross-sectional area of the
      labelled neurons (879 +/- 79 microm2). More importantly, systemic pretreatment
      with capsaicin prevented the peripheral nerve lesion-induced labelling of small
      cells. Thus, the mean cross-sectional areas of labelled neurons relating to the
      intact and transected sciatic nerves, respectively, did not differ significantly.
      These findings provide direct evidence for a phenotypic switch of capsaicin
      sensitive nociceptive neurons after peripheral nerve injury, and suggest that
      lesion-induced morphological changes in the spinal cord may be related to
      specific alterations in the chemistry of C-fibre afferent neurons rather than to
      a sprouting response of A-fibre afferents.

PMID- 12064783
TI  - A combined electrophysiological and behavioural study for the assessment of
      activity-dependent changes in mice.
AB  - Activity-dependent adaptive changes in the nervous system involve structural and
      functional changes in the cortical circuitry. In this work the cortical function
      was studied by repeated recording of the somatosensory and motor potentials
      evoked by whisker deflections after altered sensory-motor experience in adult
      mice. The latencies of motor and somatosensory evoked potentials were found to
      shorten, while their amplitudes decreased, after a behavioural challenge
      involving the vibrissal apparatus. Sensory deprivation achieved by whisker
      trimming resulted in a partial reversal of the changes observed after increased
      activity. The derived parameters imply that cortical information processing
      speeds up as a result of experience, while decreased activity has the opposite
      effect. The methods used throughout the experiment were minimally invasive, and
      thus proved to be sufficient for the long-term follow-up of cortical functions.

PMID- 12064784
TI  - Influence of passive avoidance learning by substance P in the basolateral
      amygdala.
AB  - Neuropeptide substance P (SP) has reinforcing and memory facilitating effects
      after its peripheral or central application. Rats self-inject SP into the
      ventromedial caudate-putamen and SP microinjections into the basal forebrain
      induce place preference with a simultaneous increase of dopamine level. In the
      amygdaloid body SP positive neurones and terminals have been identified. The aim
      of the present study was to examine the possible reinforcing effects of SP in the
      basolateral amygdala (ABL). CFY male rats were conditioned in two-compartment
      passive avoidance paradigm and place preference was examined in two-compartment
      box and in circular open field. Animals were microinjected bilaterally with 10 ng
      SP, 100 ng SP or vehicle solution (0.4 microl/side) into the ABL. Results showed
      that post-shock infusion of 10 ng SP significantly enhanced passive avoidance
      learning while 100 ng SP was ineffective. In two-compartment-box and in circular
      open field place preference did not develop after SP treatments, however. Our
      data are the first to demonstrate that SP in the ABL is involved in learning and
      memory processes related to aversive situations. Results that SP microinjections
      were not followed by rewarding-reinforcing consequences in place preference
      paradigms indicate that the local SP network in the ABL is not involved in
      neuronal circuitry responsible for addictive behaviour.

PMID- 12064785
TI  - Phonatory characteristics of parkinsonian speech before and after morning
      medication: the ON and OFF states.
AB  - After prolonged treatment with L-dopa, patients with Parkinson's disease (PD)
      experience fluctuations in motor performance. Changes in voice production have
      been documented perceptually during periods of fluctuation, but few quantitative
      changes have been found. The purpose of this study is to examine the acoustic
      phonatory characteristics of PD speech before and after taking medication, to
      determine if fluctuations affected phonation. Nine PD patients participated in
      this study. Multiple analyses were performed, and revealed that fundamental
      frequency (Fo) variability in vowels and mean Fo were higher, while intensity
      range was lower in PD patients compared to controls. When the PD subjects were
      examined after versus before medication, group differences were small, but
      phonatory improvements were seen in individual subjects. Discussion focuses on
      physiological changes and variability in PD, and implications of response
      fluctuations to speech production. LEARNING OUTCOMES: As a result of this
      activity, the participant will be able to (1) acquire knowledge and understanding
      of PD and the voice characteristics commonly associated with PD and (2)
      understand the effects of L-dopa-related fluctuations on voice production in PD.

PMID- 12064786
TI  - Definitional skill in school-age children with specific language impairment.
AB  - The purpose of the present study was to investigate the definitional skills in
      children with specific language impairment (SLI). Fifteen children with SLI and
      15 matched control participants were asked to define 10 common high-frequency
      nouns (e.g., apple, horse, and boat). Definitions were scored for both content
      and form. Children with SLI scored significantly lower than children with
      typically developing language for both content and form. Results suggest that
      lexical access and/or lack of metalinguistic knowledge were potential causes for
      the lower scores earned by the children with SLI when defining common nouns.
      Implications for assessment of and intervention for definitional skill are
      discussed. LEARNING OUTCOMES: The reader will be able to explain the importance
      of definitional skill and how this skill generally develops in typically
      developing children. The reader will be able to describe the performance, in
      terms of content and form, of children with SLI and their typically developing
      peers in defining common high-frequency nouns. The reader will also be able to
      discuss what possible impact linguistic knowledge, metalinguistic knowledge, and
      lexical access have on children with SLI in defining the common nouns in this
      study.

PMID- 12064787
TI  - Articulation in Prader-Willi syndrome.
AB  - This study investigated articulation in 13 individuals with Prader-Willi syndrome
      (PWS), chronological age from 7; 0 to 29; 5, total IQ from 38 to 83. To elicit a
      speech sample a picture-naming test was used. Pictures were chosen so that, when
      named correctly, they yield a sample containing instances of all Dutch single
      speech sounds and clusters in all permissible syllable positions. All samples
      were transcribed phonetically by a stringent transcription procedure, and
      reliability of the transcription was assessed both by an intra-observer and inter
      observer reliability check. The transcribed speech samples were subjected to
      several analyses as to characterize articulation from different perspectives. It
      was found that articulation in persons with PWS is usually impaired. Results
      suggest that the overall error rate is a function of IQ, and that with increasing
      age, phonological problems gradually resolve while phonetic difficulties become
      more evident. LEARNING OUTCOMES: The reader will learn about (1) clinical
      characteristics, etiology, incidence, and prevalence of Prader-Willi syndrome;
      (2) speech and language difficulties in Prader-Willi syndrome; (3) articulation
      characteristics in Prader-Willi syndrome.

PMID- 12064788
TI  - Intelligibility as a linear combination of dimensions in dysarthric speech.
AB  - Speech samples of 79 dysarthric patients (native speakers of English) were judged
      by two experienced judges by means of a perceptual rating scale covering the four
      main dimensions of speech production: voice quality, articulation, nasality and
      prosody as well as overall intelligibility. In order to determine the relative
      influence of the four basic dimensions on intelligibility in this study group, a
      multiple regression model was applied. This model shows that intelligibility can
      be expressed as a linear combination of weighted perceptual dimensions (R2 =
      0.89). This expression reveals the relative importance of the individual
      dimensions on overall intelligibility. Articulation is shown to be the strongest
      contributor to intelligibility. A group of 16 dysarthric patients (native
      speakers of Dutch) was used as a control group in order to evaluate the validity
      of the expression. Judged and calculated ratings (within the 95% prediction
      intervals) were in agreement for 75% of the patients. These findings may
      contribute in the construction of a better balanced measure of functional
      intelligibility. LEARNING OUTCOMES: 2. The impact of articulation on
      intelligibility is dominant but inclusion of the dimensions "nasality", "voice"
      and "prosody" results in a more balanced estimation of intelligibility.

PMID- 12064789
TI  - Service delivery framework for adolescents with communication problems who are
      involved in violence.
AB  - The purpose of this article is to provide speech-language pathologists (SLPs)
      with a framework to address the communication problems of adolescents involved in
      violence. Although it is not considered to be a comprehensive framework for
      planning intervention programs, it will provide suggestions to assist SLPs to
      conceptualize their role in addressing the communication needs of these
      individuals. Recommendations acquired through observations, interviews, and
      empirical data will form the basis for suggestions. Youth in correctional
      facilities come from schools and return to schools following their commitment,
      therefore, research from incarcerated adolescents serves as an appropriate
      foundation to form the basis for intervention recommendations. Hence, suggestions
      will apply to SLPs working in correctional facilities and school settings.
      Intervention programs containing socially and academically relevant activities
      that focus on assessment, general intervention principles, conversational
      interaction skills, and multidisciplinary interventions are included in the
      article. LEARNING OUTCOMES: Readers will understand (1) a framework to address
      the communication problems of adolescents involved in violence and (2) how
      research findings support the role of SLPs in addressing the needs of adolescents
      involved in violence.

PMID- 12064791
TI  - Analysis of sequence configurations of the ISDR, PKR-binding domain, and V3
      region as predictors of response to induction interferon-alpha and ribavirin
      therapy in chronic hepatitis C infection.
AB  - Interferon (IFN) and ribavirin combination therapy for chronic hepatitis C virus
      (HCV) infection yields a sustained response rate of only approximately 40%.
      Previous studies have linked IFN responsiveness to viral sequence variation in
      parts of the E2 and NS5A genes, but this remains controversial. We studied
      pretreatment sera from 28 subjects (23 with HCV genotype 1a) who received high
      dose IFN induction followed by IFN-ribavirin combination therapy. Serum HCV
      sequences were amplified and compared from 14 responders with undetectable HCV
      RNA 24 weeks after therapy and 11 nonresponders (excluding three who dropped out
      of the study). Analysis included the E2 PKR eIF-2alpha phosphorylation homology
      domain (PePHD, codons 659-670), where the sequence was well conserved, and codons
      2001-2420 of NS5A. In NS5A, the proposed PKR binding domain (codons 2209-2274),
      containing the putative IFN sensitivity determining region (ISDR, codons 2209
      2248), showed too little variation among subjects to differentiate responders and
      nonresponders. NS5A codons 2356-2385 (which includes the V3 region) exhibited
      more variation. Here, six of 12 genotype 1a responders showed four or more amino
      acid changes from the prototype HCV-1 sequence, as compared with one of eight
      nonresponders, but this fell short of statistical significance (P = 0.16). NS5A
      sequences from posttreatment sera were examined in six nonresponders to look for
      selection of treatment-resistant viral subpopulations, but no consistent change
      was detected. In conclusion, our results indicate that the sequences of the ISDR,
      the PKR-binding domain, and the PePHD are unlikely to have predictive value for
      IFN treatment success in those infected with HCV genotype 1a. However, the
      finding of greater variability among treatment responders in the carboxy end of
      NS5A suggests that the V3 region merits further investigation.

PMID- 12064792
TI  - Serum intercellular adhesion molecule-I in children with chronic liver disease:
      relationship to disease activity.
AB  - Intercellular adhesion molecule-I (ICAM-I) is a member of the immunoglobulin
      supergene family. It is expressed on the surface membrane of cells of multiple
      lineages at sites of inflammation. A soluble form of ICAM (sICAM-I) comprising
      the five extracellular Ig-like domains of ICAM-I has been detected in human serum
      and has been found to be increased in a variety of acute and chronic liver
      disorders. However, little is known about sICAM-I levels in children with chronic
      liver disease. Therefore, we measured sICAM-I in 23 children with chronic
      hepatitis, 14 children with cirrhosis, and 10 age- and sex-matched normal
      children by commercially available ELISA. We also correlated the sICAM-I levels
      with the histological activity index (HAI) score as determined from liver
      biopsies. Patients with chronic hepatitis had higher sICAM-I levels compared to
      controls (723 +/- 272 ng/ml vs 282 +/- 43 ng/ml, mean +/- SD; P < 0.05). sICAM-I
      levels were also higher in patients with cirrhosis compared to controls (630 +/-
      218 ng, mean +/- SD; P < 0.05). However, there was no significant difference
      between sICAM levels in patients with chronic hepatitis and cirrhosis. A
      significant correlation was found between the ICAM-I level and the histological
      activity index score in patients with chronic hepatitis (r = 0.58; P < 0.001) and
      in patients with cirrhosis (r = 0.7; P < 0.001). We also found that by using the
      cutoff level of 346 ng/ml, sICAM-I can be used as a screening test with high
      specificity (100%) and sensitivity (94%) to differentiate children with chronic
      liver disease from normal children. We conclude that sICAM is increased in
      children with chronic hepatitis and cirrhosis compared to controls. The degree of
      elevation correlates with the HAI score. sICAM may be used as a marker of the
      disease activity and may provide diagnostic and prognostic information in
      children with chronic liver disease. However, this needs to be further studied.

PMID- 12064790
TI  - Hepatitis A, hepatitis B, and combination hepatitis vaccines for
      immunoprophylaxis: an update.
AB  - Since the publication of the last extensive review of hepatitis vaccines, use of
      inactivated hepatitis A vaccines has been extended to high-risk regions of the
      United States and specific patient groups, such as those with chronic liver
      disease, and use of the recombinant hepatitis B vaccines has been recommended for
      older adolescents. A combination hepatitis A and B vaccine, recently approved for
      licensure by the US Food and Drug Administration, should increase convenience and
      compliance, reduce the costs of vaccination, and provide prolonged and dual
      protection for those at risk for hepatitis. Although commercially available
      vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and
      adjuvant technology, including immunization with DNA-based vaccines, hold promise
      for the future.

PMID- 12064793
TI  - Up-regulation of CD11a (LFA-1) expression on peripheral CD4+ T cells in primary
      biliary cirrhosis.
AB  - Up-regulation of CD11a expression on CD4+ T lymphocytes is considered to be one
      of the mechanisms involved in the initiation of the Th-1-mediated immune
      response. In this study, peripheral blood mononuclear cells from patients with
      primary biliary cirrhosis (PBC) were evaluated for CD11a(high) CD2(low) T cells
      and populations of type 1 (Th-1) and type 2 (Th-2) helper T cells. CD11a(high)
      CD2(low) T cells were found in PBC (7/15) and in active rheumatoid arthritis
      (4/4), but not in chronic hepatitis C (0/5) or in healthy subjects (0/6). The
      population of Th-1 had a positive correlation with that of CD4+ CD11a(high) CD2+
      cells in patients with PBC (P = 0.034). The serum levels of interferon-gamma also
      had a weak correlation with the population of CD4+ CD11a(high) CD2(low) cells (P
      = 0.050). There was no statistically significant correlation of Th-2 population
      (P = 0.295) or serum interleukin-4 level (P = 0.685) with the population of CD4+
      CD11a(high) CD2(low) cells. These results suggest that CD4+ CD11a(high) cells
      play a role in Th-1-predominance and in the autoimmune process of PBC.

PMID- 12064794
TI  - Experimental colitis attenuates development of toxin-induced cholangitis in rats.
AB  - Primary sclerosing cholangitis frequently occurs in association with ulcerative
      colitis. This close association may be due to colitis predisposing patients to
      bile ductular injury. Therefore, we determined the susceptibility of rats with
      experimental colitis to toxin-induced cholangitis. Sprague-Dawley rats received
      2,4,6-trinitrobenzene-sulfonic-acid (TNBS) or ethanol vehicle intracolonically.
      Seven days later, rats received either the biliary epithelial cell toxin alpha
      naphthylisothiocyanate (ANIT) or vehicle and were killed 24 hr later. Liver
      histology, serum biochemistries and tumor-necrosis factor-alpha (TNF-alpha), and
      hepatic interleukin-10 (IL-10) mRNA were determined. TNBS-treated rats showed
      extensive macroscopic colonic damage and a 10-fold increase in myeloperoxidase
      activity compared to ethanol-treated controls. ANIT-treated noncolitic rats
      showed portal inflammation centered on damaged bile ducts (cholangitis), which
      was markedly attenuated in ANIT-treated colitic rats. Hepatic IL-10 mRNA was
      twofold higher in colitic compared to noncolitic rats, with no difference in
      serum TNF-alpha. In conclusion, experimental colitis attenuates the development
      of toxin-induced cholangitis in rats, possibly by up-regulating hepatic IL-10
      expression.

PMID- 12064795
TI  - Chronic hepatitis C and autoimmune cholangitis: a case study and literature
      review.
AB  - We present a case of a chronic hepatitis C with damage of bile ducts resembling
      primary biliary cirrhosis. The immunological profile (negative antimitochondrial
      antibodies and positive anti-nuclear antibody) was characteristic of the
      autoimmune cholangitis. One year of treatment with ursodeoxycholic acid returned
      the liver tests to the normal range but the liver lesions remained unchanged.

PMID- 12064796
TI  - Juvenile idiopathic fibrosing pancreatitis.
AB  - Chronic pancreatitis is a rare differential diagnosis of obstructive jaundice
      and/or recurrent abdominal pain in childhood and adolescence. The hereditary
      calcifying and the noncalcifying obstructive form are the two major forms of
      juvenile chronic pancreatitis. Other causes include cystic fibrosis,
      hyperparathyroidism, hyperlipoproteinemia and ascariasis. Even less common is the
      so called idiopathic or fibrosing pancreatitis. Since the first description by
      Comfort in 1946 only 41 further cases of juvenile idiopathic fibrosing
      pancreatitis have been published. An association with gene mutations (PRSS1,
      SPINK1, CTFR-5T genotype) is suspected. We report the cases of a 17-year-old male
      patient who presented with painless obstructive jaundice and a 16-year-old female
      patient who presented with abdominal pain and obstructive jaundice. Both patients
      underwent surgical treatment with duodenum-preserving pancreatic head resection.
      The relevant literature with special regard to modern pancreatic surgery is
      reviewed to give an overview about this rare but surgically treatable pediatric
      condition, which merits the attention of pediatricians and gastroenterologists in
      cases of children and adolescents suffering from unexplained abdominal pain.

PMID- 12064797
TI  - Noninvasive colorectal cancer screening.
AB  - Abnormal mucin with the STn epitope is produced by colorectal cancer cells and is
      immunologically distinguishable from normal colonic mucin. Herein we describe a
      technique of detecting abnormal mucin in fecal samples as a method of screening
      for colorectal neoplasia. Soluble glycoproteins from fecal samples of patients
      with symptoms of bowel disease and asymptomatic volunteer subjects were isolated
      by centrifugation and ethanol precipitation. The protein content of the soluble
      fraction was normalized and tested by immunoassay (slot dot). Anti-COTA
      monoclonal antibody SP-21, which reacts with STn epitope, was applied in the
      reaction, and the optical density of each slot dot was determined by imaging
      densitometer. Quantitative values of samples were determined from the standard
      curve obtained with highly purified COTA. COTA values > 15 microg/ml were
      considered positive for neoplasia. Results indicated that 5/6 colon cancers, 6/22
      adenomas, 1/8 colitis cases, and 2/58 normal patients were positive in the test.
      The pilot study revealed that COTA assay is sensitive and more specific than
      Hemoccult screening for colorectal neoplasia.

PMID- 12064798
TI  - Effect of gastrointestinal reconstruction on quality of life and nutritional
      status after pylorus-preserving pancreatoduodenectomy.
AB  - A total of 31 Japanese patients who underwent pylorus-preserving
      pancreatoduodenectomy from January 1998 through September 2000 were studied
      regarding quality of life and nutritional status before and within two months
      (short term) and six months to one year (long term) after surgery. Quality of
      life was estimated using a questionnaire consisting of 23 items (13 physical and
      10 psychosocial domains). Nutritional status was assessed by body weight,
      hemoglobin concentration, serum concentration of albumin and cholesterol, and
      pancreatic function. These data were compared between 18 patients with end-to-end
      (Imanaga) and 13 with end-to-side (Traverso) gastrointestinal reconstruction. In
      both groups, physical quality of life scores dropped at short term, and then
      returned to the normal level at long term after operation, showing mostly
      parallel changes with the parameters of nutritional status. However, the scores
      of psychosocial conditions, which reflected the patient's mental health, remained
      low even at long term in both groups. The values of these parameters showed no
      statistical difference between the two groups at each time point. Postoperative
      quality of life and nutritional status were not different between Imanaga and
      Traverso reconstructions after pylorus-preserving pancreatoduodenectomy and
      mental health care would be necessary for at least one year after operation in
      both groups.

PMID- 12064799
TI  - Expression of G1 phase cyclins in human gastric cancer and gastric mucosa of
      first-degree relatives.
AB  - The aim of this study was to investigate the expression of D-type cyclins and
      cyclin E in gastric cancer patients (N = 34), in healthy first-degree relatives
      of gastric cancer patients (N = 29), and in control subjects (N = 18). Expression
      of cyclins D1, D2, D3, and E was determined by RT-PCR. Localization of cyclin
      expression was determined by immunohistochemistry. Expression of cyclins D2, D3,
      and E was more frequently detected in tumor tissue compared with tumor-free
      gastric mucosa (P < 0.05) and was associated with the presence of intestinal
      metaplasia. In contrast, cyclin D1 was frequently expressed in both tumor- and
      tumor-free tissue. Cyclin D3 expression was more frequently detected in the
      antrum mucosa of first-degree relatives compared to controls (P < 0.01) and was
      associated with the presence of Helicobacter pylori. Our data suggest that
      deregulation of G1 phase cyclins may play a role in gastric carcinogenesis, and
      may point to the presence of molecular alterations in individuals at an increased
      risk for gastric cancer.

PMID- 12064800
TI  - Inhibitory effect of small amounts of cellulose on colonic carcinogenesis with
      low-dose carcinogen.
AB  - This study set out to evaluate the effects of dietary fiber on cancer development
      in the large bowel under in vivo experimental conditions as similar as possible
      to those under which this cancer develops in vivo in humans. Forty-eight Sprague
      Dawley rats were divided into three groups that were fed either a nonfiber diet
      or a 3 g or 10 g/100 g cellulose diet in this experiment, and all groups received
      doses of a mild carcinogen, 1,2-dimethylhydrazine (5 mg/kg body weight) for 50
      weeks. Following endoscopic observation of the large bowel, we found that the
      induction rates of tumor in the cellulose groups were significantly lower than
      that in the nonfiber diet group, both endoscopically and histologically. No
      differences were seen between the 3% and 10% cellulose groups in suppressing
      carcinogenesis. It is likely that the inhibitory effect of 3% cellulose could be
      confirmed only by a long-term experiment on carcinogenesis following the
      administration of a low dose of carcinogen.

PMID- 12064801
TI  - Dietary iron supplementation enhances DSS-induced colitis and associated
      colorectal carcinoma development in mice.
AB  - Chronic ulcerative colitis (UC) patients frequently require iron supplementation
      to remedy anemia due to blood loss. However, the effect of iron supplementation
      on UC-associated carcinogenesis is unknown. In this study, the effect of an iron
      enriched diet on dextran sulfate sodium-induced acute and chronic colitis in mice
      was assessed. In a short-term study, mice administered 1% DSS in the drinking
      fluid and an AIN76A diet containing increasing levels of iron exhibited dose
      dependent increases in the severity of acute UC as compared to mice fed a control
      diet. A marked increase in iron deposition on the epithelial surface of the colon
      and in the inflamed areas and immunostaining for iNOS and nitrotyrosine were
      observed in the animals supplemented with diets containing different levels of
      iron. In a long-term carcinogenesis experiment, a twofold iron-enriched diet
      significantly increased colorectal tumor incidence (14/16, 88%) as compared with
      animals fed the control diet (3/16, 19%; P < 0.001). The present findings have
      implications for the management of human UC and suggest that dietary iron can
      enhance UC and its associated carcinogenesis by augmenting oxidative and
      nitrosative stress.

PMID- 12064802
TI  - Short-term intestinal ischemia-reperfusion alters intestinal motility that can be
      preserved by xanthine oxidase inhibition.
AB  - While the effects of transient intestinal ischemia on mucosa have been well
      investigated, less is known about its effect on motor function. An experimental
      study was designed to investigate the effects of ischemia-reperfusion (I/R) on
      intestinal motility and intestinal muscular microcirculation. Wistar albino rats
      were divided into four groups: (1) baseline, (2) sham operation, (3) I/R, and (4)
      I/R with allopurinol pretreatment. Ischemia was induced by clamping the superior
      mesenteric artery (SMA) for 10 min. Gastroanal transit time (GATT) was measured
      with serial x-rays after instillation of barium sulfate to the stomach.
      Intestinal muscular microcirculation was evaluated by determining the number of
      carbon-perfused intestinal muscular microvessels (CPIMM). I/R prolonged GATT and
      decreased CPIMM significantly (P < 0.01). Pretreatment with allopurinol prevented
      prolongation of GATT and returned the number of CPIMM to the level of sham
      treatment (P < 0.01). In conclusion, reperfusion after 10 min of SMA ischemia
      alters intestinal motility. The no-reflow phenomenon plays an important role in
      this alteration of motility. Administration of allopurinol before reperfusion
      preserves intestinal motility by preventing the occurrence of no-reflow
      phenomenon.

PMID- 12064803
TI  - Involvement of serotonin and nitric oxide in endotoxin-induced gastric motility
      changes in conscious rats.
AB  - Severe bacterial infection causes gastrointestinal dysmotility by an unknown
      mechanism. We investigated the possible involvement of serotonin (5-HT) and
      nitric oxide (NO) in endotoxin-induced motility disturbance, using an in vivo rat
      model. Six days prior to the experiment, a force transducer was sutured to the
      gastric antrum of rats. Lipopolysaccharide induced strong repetitive contractions
      in the gastric antrum within 2 to 3 min in all rats tested. After 15 min of
      hypermotility, motility decreased and remained low for more than 60 min. The
      initial increase in motility was suppressed by atropine, FK1052, or SB204070,
      whereas it was not affected by granisetron. The subsequent decrease was inhibited
      by L-NAME and S-methylisothiourea sulfate. These results indicate that in
      conscious rats, lipopolysaccharide induces a transient increase in gastric
      motility followed by suppression. The increase might be mediated by 5-HT4
      receptors, and the decrease by inducible NOS.

PMID- 12064804
TI  - Two-dimensional positional mapping of gastrointestinal sounds in control and
      functional bowel syndrome patients.
AB  - Computerized auscultation of the abdomen provides a noninvasive and quantitative
      method to investigate gastrointestinal function. Two-dimensional mapping of bowel
      sound sites of origin, to the surface of the abdomen, was accomplished through
      simultaneous recording with three electronic stethoscopes. Control, irritable
      bowel syndrome, and nonulcer dyspepsia groups were studied. The predominant site
      of fasting sound production was the right lower quadrant in all except a subgroup
      of nonucler dyspepsia patients. The second most common site mapped to the area of
      the stomach. The region mapping to the small intestine was largely devoid of
      sound. The control group had a higher percentage of sounds in the 184- to 248-Hz
      range than the functional bowel patients (P < 0.001) for sounds mapping to the
      stomach region. We conclude that two-dimensional mapping may have the potential
      to allow for the meaningful and objective categorization of groups of functional
      bowel patients.

PMID- 12064805
TI  - Group counseling psychotherapy for patients with functional gastrointestinal
      disorders: development of new measures for symptom severity and quality of life.
AB  - Functional gastrointestinal disorders (FGID) can benefit from various
      psychological interventions. The main objective here was to define the
      contribution of a new psychotherapeutic intervention, group counseling
      psychotherapy, for the management of FGID patients. Secondary aims included
      validation of new measures for gastrointestinal symptoms and quality of life in
      patients with FGID. Fifty patients seen in a tertiary care center were included
      in a program of 10 weekly sessions of 2 hr each. Gastrointestinal symptoms,
      quality of life, and psychological conditions were measured before and after
      treatment by quantitative indices and by qualitative self-analysis.
      Gastrointestinal index and quality-of-life index were significantly (P < 0.02)
      improved at the end of the psychotherapeutic intervention (from 77.5 +/- 4.0 to
      63.2 +/- 4.3 and from 67.7 +/- 3.9 to 54.9 +/- 3.9, respectively). In a control
      group of patients observed for a comparable period of time while waiting for the
      psychotherapy program, gastrointestinal and quality of life indices remained
      unchanged. The severity of gastrointestinal symptoms and the quality of life
      deterioration were highly correlated factors (r = 0.8) at entry into the trial,
      and their improvement with psychotherapy was also correlated (r = 0.6; P <
      0.001). Psychological abnormalities were frequent in these patients (anxiety in
      31%, somatization in 29%, depression in 26% of the patients). However, no
      specific disorder could predict the results of the psychotherapeutic
      intervention. Over the long term (6-24 months after conclusion of treatment),
      gastrointestinal status, quality of life, and psychological condition were
      estimated as improved by 53%, 63%, and 67% of the patients, respectively. The
      gastrointestinal index and quality of life index we developed were validated to
      detect the disease and to follow its evolution in response to treatment. In
      conclusion, group counseling psychotherapy offered a significant contribution for
      the management, improving gastrointestinal symptoms and quality of life, of FGID
      patients. New measures for symptom severity and quality of life are available.

PMID- 12064807
TI  - Tumor necrosis factor-alpha mediates inhibitory effect of lipopolysaccharide on L
      leucine intestinal uptake.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has been proposed as an early proximal
      mediator of many metabolic and physiologic responses during septic shock. We have
      previously shown that direct addition to tissue (local effect) or intravenous
      administration (systemic effect) of lipopolysaccharide (LPS) reduces L-leucine
      absorption across rabbit jejunum. In the present study, we investigated whether
      the inhibitory effect of LPS on L-leucine intestinal absorption in rabbit is
      related to TNF-alpha. The results shown that the addition of TNF-alpha to tissue
      does not produce any effect on L-leucine uptake by the enterocyte. When TNF-alpha
      was inoculated by intravenous administration, a strong inhibition on the L
      leucine uptake (about 40%), mediated by a secretagogue effect on water and Cl
      ions was induced. We also found that the LPS intestinal effect induced by
      intravenous administration, was blocked by a TNF-alpha antagonist, indicating
      that TNF-alpha is a mediator of the LPS systemic effect on L-leucine intestinal
      uptake inhibition. The study of possible mediators involved in the TNF-alpha
      effect showed that nitric oxide and prostaglandins are implicated in the L
      leucine intestinal uptake.

PMID- 12064808
TI  - Anaphylaxis-like reaction to infliximab in a patient with Crohn's disease.

PMID- 12064806
TI  - Pathways involved in mild gastrointestinal inflammation induced by a low level
      exposure to a food contaminant.
AB  - Chronic gut inflammation is associated with radical oxygen species (ROS) genesis.
      ROS may activate certain transcription factors such as nuclear factor kappa beta
      (NF-kappaB), which regulates cyclooxygenase-2 (COX-2). Diquat, a food
      contaminant, is responsible for oxidative stress. This work aimed to establish
      the involvement of ROS and prostanoids on diquat-induced gastrointestinal
      inflammation and mast cell hyperplasia. Diquat increased gastrointestinal MPO
      activity and mast cell number. Its effect on gastric MPO activity was reversed by
      PD 138,387 (a COX-2 selective inhibitor) and PDTC (an inhibitor of NF-kappaB
      activation) but not by DMSO (a hydroxyl radical scavenger) and allopurinol (a
      xanthine oxidase inhibitor). In contrast, increased jejunal MPO activity was
      blocked by both DMSO, PD 138,387, and PDTC, while allopurinol enhanced it. PD
      138,387 and PDTC reduced gastrointestinal mast cell number while DMSO and
      allopurinol did not Diquat-induced inflammation involves a gastrointestinal NF
      kappaB activation and COX-2 dependent proinflammatory prostanoid synthesis.
      Furthermore, the hydroxyl radical is involved in intestinal but not gastric
      inflammation.

PMID- 12064809
TI  - Sugar alcohols enhance calcium transport from rat small and large intestine
      epithelium in vitro.
AB  - We compared the effect of a variety of sugar alcohols on calcium absorption from
      the rat small and large intestine in vitro. An Ussing chamber technique was used
      to determine the net transport of Ca across the epithelium isolated from the
      jejunum, ileum, cecum, and colon of rats. The concentration of Ca in the serosal
      and mucosal Tris buffer solution was 1.25 mM and 10 mM, respectively. The Ca
      concentration in the serosal medium was determined after incubation for 30 min
      and the net Ca absorption was evaluated. The addition of 0.1-200 mM erythritol,
      xylitol, sorbitol, maltitol, palatinit, or lactitol to the mucosal medium
      affected net Ca absorption in the intestinal preparations. Differences in Ca
      transport were observed between portions of the intestine, but not between sugar
      alcohols tested. We concluded that sugar alcohols directly affect the epithelial
      tissue and promote Ca absorption from the small and large intestine in vitro.

PMID- 12064810
TI  - Immunomodulatory effects of granulocyte and monocyte adsorption apheresis as a
      treatment for patients with ulcerative colitis.
AB  - Our aim was to understand the mechanism of immunological changes associated with
      the use of an adsorptive-type extracorporeal device (Adacolumn) that has been
      developed for selective adsorption of granulocytes and monocytes/macrophages from
      peripheral blood of patients with active ulcerative colitis. The column is filled
      with carriers (G-1 beads) that have a diameter of 2 mm and are made of cellulose
      diacetate. In peripheral blood treated with the G-1 beads or peripheral blood
      from patients with active ulcerative colitis following granulocyte and monocyte
      adsorption apheresis, a significant suppression of proinflammatory cytokines
      (tissue necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin
      8) production by leukocytes, neutrophil chemotaxis, down-regulation of leukocyte
      adhesion molecule (L-selectin) and neutrophil adhesion to interleukin-1beta
      activated endothelial cells were observed. Furthermore, after granulocyte
      adsorption therapy, the number of CD10-negative premature granulocytes increased,
      indicating increased turnover of these cells in the circulation. Our observations
      suggest that selective granulocyte and monocyte adsorption is associated with
      modified peripheral blood leukocyte function favorable to patients with
      ulcerative colitis and possibly other autoimmune disorders which reflect
      leukocyte hyperactivity.

PMID- 12064811
TI  - Modulatory effects of plasma and colonic milieu of patients with ulcerative
      colitis on neutrophil reactive oxygen species production in presence of a novel
      antioxidant, rebamipide.
AB  - Rebamipide protects gastrointestinal mucosal integrity against reactive oxygen
      species (ROS). The effect of rebamipide on the capability of PMNs to produce ROS
      in the presence of plasma and rectal dialysates (RD) of control and ulcerative
      colitis (UC) subjects was evaluated. We recruited six healthy volunteers for
      obtaining PMNs, control plasma, and control RD and six patients with inactive UC
      for obtaining plasma and RD. PMNs were activated using fMLP, and ROS was measured
      by fluorescent microplate assay (DCFD). Rebamipide significantly inhibited the
      neutrophil respiratory burst by 45%. Plasma from both control subjects and UC
      patients significantly blunted the fMLP-induced respiratory burst. However, the
      plasma of the UC patients was significantly less inhibitory than the plasma of
      control subjects. RD from control subjects significantly blunted the fMLP-induced
      respiratory burst while, RD from patients with UC did not. Rebamipide maintained
      its antioxidant effects in the presence of plasma or RD obtained from both
      controls and UC patients. In conclusion, partial loss of the inhibitory effects
      of plasma and RD in patients with UC may contribute to oxidative-induced tissue
      damage in UC and rebamipide antioxidant properties were not hampered by the
      biological milieu of patients with UC.

PMID- 12064812
TI  - Innate immunity and colonic inflammation: enhanced expression of epithelial alpha
      defensins.
AB  - Human alpha-defensins contribute to local intestinal host defense as part of
      innate immunity and may be of major relevance in microbial infection and chronic
      inflammatory bowel disease. The objective was to investigate human defensin 5 and
      6 (HD-5, HD-6) mRNA expression by RT-PCR from colonic biopsies and peptide
      expression by immunohistochemistry from colonic resections under basal and
      inflammatory conditions. Both alpha-defensins were induced by proinflammatory
      cytokines in cell culture. HD-5 mRNA expression was enhanced in both idiopathic
      and nonidiopathic inflammatory states of the large bowel [32% of control vs 73%
      of unspecific colitis, 69% of Crohn's disease (CD) and 73% of ulcerative colitis
      (UC)], whereas HD-6 was specifically related to CD and UC (14% in controls vs 20%
      in unspecific coltis, 49% in CD and 42% in UC). Immunohistochemistry confirmed
      the presence of HD-5 in colonic epithelium. Antimicrobial peptides in the colon
      may be of importance in maintaining the mucosal barrier and controlling microbial
      invasion in inflammatory bowel diseases.

PMID- 12064814
TI  - Effect of cyclosporine in a murine model of experimental colitis.
AB  - The use of immunosuppressive therapy may be associated with significant toxicity.
      The aim of this study was to investigate the effect of cyclosporine A (CsA) in
      murine model of experimental colitis. Experimental colitis was induced in NMRI
      mice using an enema of 0.2% solution of dinitrofluorobenzene, combined with skin
      sensitization. After inducing colitis, experimental groups of animals were
      treated with CsA (1, 3, 5, 10, 25, 50 mg/kg/day) intraperitoneally (i.p.) or
      intracolonically (i.c.), and control groups were treated with phosphate-buffered
      saline intraperitoneally or intracolonically, respectively. Colonic inflammatory
      changes were assessed using a histopathologic score of 0-30, and pooled whole
      blood samples were processed with monoclonal antibodies for cyclosporine
      concentration. In addition, two groups of animals with experimental colitis were
      treated intraperitoneally or intracolonically with 3 mg/kg/day of CsA, and the
      colons were also taken for immunohistochemistry for CD25. CsA diminished the
      extent of colitis in groups treated with 3, 5, 10, or 25 mg/kg intraperitoneally
      or intracolonically, and in groups treated with 1 and 50 mg/kg intracolonically
      (P < 0.05). The effect of intracolonic application of CsA was not related to
      whole blood cyclosporine concentrations. In addition, the effect of CsA at 3
      mg/kg, applied intraperitoneally or intracolonically was, in part, expressed in
      decreasing the numbers of CD25+ cells within colonic mucosa/submucosa (P < 0.05).
      In conclusions, the results of this study indicate the possibility of
      intracolonic application of cyclosporine in order to widen the therapeutic window
      for effective, but possibly toxic drug, such as cyclosporine.

PMID- 12064813
TI  - Daily norfloxacin is more effective than weekly rufloxacin in prevention of
      spontaneous bacterial peritonitis recurrence.
AB  - Our aim was to compare weekly rufloxacin with daily norfloxacin in the secondary
      prophylaxis of spontaneous bacterial peritonitis and to examine changes in
      antibiotic susceptibility in fecal Escherichia coli. The method used was an open
      randomized clinical trial including 79 patients who received either norfloxacin
      400 mg/day or rufloxacin 400 mg/week and followed up for one year. E. coli
      counts, quinolone susceptibility, and drug concentrations in feces were
      investigated in 12 patients. Cumulative one-year probability of peritonitis
      recurrence was 26% for patients on norfloxacin and 36% for those on rufloxacin (P
      = 0.16). Norfloxacin was more effective in the prevention of peritonitis
      recurrence due to Enterobacteriaceae (0% vs 22%, P = .01). At the end of follow
      up, all 12 patients had E. coli resistant to quinolones in their feces. In
      conclusion, weekly rufloxacin is not an alternative to daily norfloxacin in the
      prevention of peritonitis recurrence. The development of quinolone-resistant E.
      coli in feces may be an important problem in patients on long-term quinolone
      prophylaxis.

PMID- 12064815
TI  - Effect of acid perfusion on passive electrophysiological properties of rabbit
      esophagus in vivo.
AB  - In the present paper we studied early acid-induced changes in the passive
      electrical properties of the rabbit esophageal epithelium in vivo by measurements
      of the transluminal potential difference (PD) during acid perfusion and by
      estimating the transmucosal electrical resistance (Rm) using cable analysis.
      Perfusion with acid (pH 1) for 45 min produced a rapid (<1 min) negative shift in
      the lumen-negative PD followed by a slow lumen-negative drift. The acid-induced
      change in PD was dependent on the accompanying anion, the largest anion (sulfate)
      producing the largest change. The acid-induced changes in PD were parallelled by
      reductions in Rm, these reductions also being dependent on the accompanying
      anion. Interpretation of resistance and net current (estimated by Ohm's law) time
      curves suggest that the initial acid-induced changes of the PD reflect properties
      of the naive mucosa whereas the later drift will reflect a diffusion driven
      increase in transmucosal proton permeability. Further, coapplication of the
      protective drug sucrose octasulfate attenuated the hydrochloric acid-induced
      changes of all measured and estimated electrophysiological parameters. The
      electrophysiological results were to some extent corroborated by light
      microscopic findings, although no large acid-induced change in mucosal appearance
      was observed.

PMID- 12064816
TI  - Diagnosis of nutcracker esophagus, segmental or diffuse hypertensive patterns,
      and clinical characteristics.
AB  - Different criteria have been used for the diagnosis of nutcracker esophagus, but
      the clinical importance of this is largely unknown. To this end, 45 patients with
      hypertensive esophageal peristalsis were identified from 572 esophageal
      investigations, and thereafter explored with regard to diagnostic criteria and
      clinical background data. The numbers of patients classified as having nutcracker
      esophagus with different criteria were 25 (by Richter criteria), 39 (by Achem
      criteria), and 45 (by Gothenburg criteria). In comparison with patients with
      segmental hypertensive peristalsis, patients with diffuse hypertensive
      peristalsis were more often referred for chest pain (P < 0.05), less often for
      reflux symptoms (P < 0.05), and tended to have arterial hypertension less often
      (P < 0.08). In conclusion, the choice of criteria for the diagnosis of nutcracker
      hypertensive peristalsis has prominent effects on the number of patients
      receiving this diagnosis. Moreover, a diffuse nutcracker peristaltic pattern
      appears more strongly linked to chest pain.

PMID- 12064817
TI  - Effects of dipyrone on inflammatory infiltration and oxidative metabolism in
      gastric mucosa: comparison with acetaminophen and diclofenac.
AB  - In the last several years, it has been proposed that neutrophil- and oxygen
      dependent microvascular injuries may be important factors in the gastrointestinal
      toxicity of nonsteroidal antiinflammatory drugs (NSAIDs). In addition, after oral
      administration, reduced levels of gastric mucosal adenosine triphosphate in
      response to mitochondrial damage constitute the earliest event on topical mucosal
      erosions. In these experiments, we compared the implication of active oxygen,
      lipid peroxidation levels and neutrophil infiltration in gastric mucosal injury
      induced by the analgesic-antipyretic drugs, dipyrone (pyrazolone derivative) and
      acetaminophen (nonacidic drug), both with relatively weak antiinflammatory
      effects, with diclofenac (an acidic NSAID). After 6 hr of oral administration,
      dipyrone (120 and 500 mg/kg) did not provoke macroscopic lesions on rat gastric
      mucosa. Only the highest dose (1000 mg/kg) induced slight erosions similar to the
      same dose of acetaminophen without modifications in lipid peroxidation levels or
      myeloperoxidase activity. The area of mucosa with lesions, the increase in
      neutrophil infiltration, and concentration of TBA-reactive substances was
      significantly higher with diclofenac (50 mg/kg). By contrast, inhibition in
      superoxide dismutase activity was observed. In a dose-dependent manner, dipyrone
      and diclofenac decreased the levels of endogenous gluthatione, and the highest
      dose (1000 mg/kg) also inhibited glutathione peroxidase activity. None of
      treatments induced changes in xanthine oxidase activity, an index of ischemic
      condition. These findings confirm the favorable gastric tolerability of dipyrone,
      since only the highest dose produced weak mucosal lesions similar to that
      obtained with acetaminophen, and this effect only could be related to a
      diminished glutathione metabolism. In contrast, diclofenac induced significant
      erosions, and the data obtained indicate that the enhancement of oxidative stress
      plays an important role in the pathogenesis of damage.

PMID- 12064818
TI  - Local gastric and serum concentrations of rebamipide following oral ingestion in
      healthy volunteers.
AB  - The purpose of this study was to investigate whether sufficient concentrations of
      rebamipide (COR) are actually present in the stomach after its oral ingestion at
      an ordinary clinical dose. Twenty healthy volunteers (total 42 man-days)
      participated in the study. After ingestion of 100, 200, or 300 mg of rebamipide,
      endoscopy was performed at 1, 2, 4, and 6 hr, and gastric mucosa or gastric mucus
      was taken from the antrum. Venous blood samples were taken simultaneously.
      Samples were analyzed by high-performance liquid chromatography. The COR in the
      gastric mucosa and gastric mucus did not depend on the original amount ingested.
      After ingestion of rebamipide, each COR was higher than 10(-4) M (37 microg/g
      tissue) at 1 or 2 hr. On the other hand, the COR in serum did depend on the
      amount ingested and was lower than 10(-6) M (0.37 microg/ml) at every time
      tested. These results suggest that the COR in the stomach exceeds the levels that
      are needed for various antiulcer actions and that the rebamipide levels present
      in the gastric mucosa and gastric mucus result from local penetration.

PMID- 12064819
TI  - Helicobacter pylori-induced oxidative stress and DNA damage in a primary culture
      of human gastric mucosal cells.
AB  - Helicobacter pylori has been identified in the pathogenesis of chronic active
      gastritis and peptic ulcer disease and is epidemiologically linked to gastric
      cancer and lymphoma. Our previous studies have demonstrated enhanced production
      of reactive oxygen species (ROS) in cultured gastric adenocarcinoma cells (ATCC
      CRL/1739) in association with H. pylori. Recently, we have isolated and cultured
      normal human gastric mucosal cells (GMC) from H. pylori-negative endoscopic
      biopsies. The integrity of these mucosal cells was determined by periodic acid
      Schiff staining. We assessed the effects of various H. pylori strains including
      60190 (a 87-kDa cytotoxin producing strain), ATCC 43504, and 60190-v1 (in which
      the cytotoxin gene has been disrupted) on the primary culture of human gastric
      mucosal cells. The induction of ROS and DNA fragmentation in the mucosal cells in
      association with these H. pylori strains were assessed by cytochrome c reduction
      (an index of superoxide anion production), hydroxyl radical production, and DNA
      fragmentation. Following incubation of the mucosal cells with 1:0.5 and 1:1
      ratios of H. pylori strain 60190, approximately 6.2- and 9.9-fold increases were
      observed in cytochrome c reduction, respectively, as compared to mucosal cells in
      the absence of H. pylori, demonstrating the production of superoxide anion. The
      detection of hydroxyl radicals based on the formation of 2,3-dihydroxybenzoic
      acid and 2,5-dihydroxybenzoic acid was determined by using a high-performance
      liquid chromatograph equipped with an electrochemical detector. Approximately 3.5
      and 7.7-fold increases in hydroxyl radical production were observed following
      incubation of the mucosal cells with 1:0.5 and 1:1 ratios of H. pylori,
      respectively. Approximately 3.6- and 4.5-fold increases in DNA fragmentation were
      observed in gastric mucosal cells following incubation with 1:0.5 and 1:1 ratios
      of H. pylori, respectively. The effects of culture supernatant preparations from
      H. pylori strains 60190 and 60190-v1 on the enhanced production of ROS and
      increased DNA fragmentation in mucosal cells were also investigated. Culture
      supernatant preparations, the prime source of the 87-kDa cytotoxin, from both H.
      pylori strains 60190 and 60190-v1 were extracted under identical conditions to
      determine the role of 87-kDa cytotoxin on the enhanced production of ROS and DNA
      fragmentation. The cytotoxin rich-H. pylori strain 60190 induced greater
      production of ROS and DNA fragmentation in mucosal cells as compared to the
      supernatant preparation from H. pylori strain 60190-v1, in which the cytotoxin
      gene has been disrupted. This study demonstrates that H. pylori induces enhanced
      production of ROS and DNA damage in association with human gastric mucosal cells
      and that the 87-kDa cytotoxin protein plays a prime role in the induction of
      oxidative stress and DNA damage.

PMID- 12064821
TI  - Who should look after patients with mild lupus?

PMID- 12064820
TI  - Phosphoglyceride crystal deposition disease presenting as multiple paragastric
      masses.

PMID- 12064822
TI  - Is it time for rheumatologists to rethink the use of manual therapies?

PMID- 12064823
TI  - Ankylosing spondylitis: what do we really know about the onset and progression of
      this disease?

PMID- 12064824
TI  - Aberrant responsiveness to RANTES in synovial fluid T cells from patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To study expression and function of the chemokine receptor CCR5 in
      synovial fluid (SF) T cells from patients with rheumatoid arthritis (RA).
      METHODS: Expression of CCR5 was studied by flow cytometry and immunoblotting. The
      chemotactic response of T cells to chemokines was studied in cell migration
      assay. Tyrosine phosphorylation of Crk-associated substrate lymphocyte-type
      (CasL) was evaluated in immunoprecipitation and immunoblotting. RESULTS: SF T
      cells showed an increase in the population of CCR5, CXCR4, and CD45RO positive
      cells and exhibited an increase in chemotactic activity, which was not augmented
      with RANTES but stromal cell-derived factor-1alpha. Tyrosine phosphorylation per
      CasL molecule was markedly enhanced in SF T cells. In H9 cells, tyrosine
      phosphorylation of not only focal adhesion kinase but also CasL was induced after
      treatment with RANTES. Downmodulation of CCR5 by RANTES was decreased and
      recycling of CCR5 was accelerated in SF T cells when compared with peripheral
      blood (PB) T cells. When CD45RO positive PB T cells were cultured with
      interleukin 2, blunted responsiveness to RANTES-induced chemotaxis was reproduced
      as well as spontaneous chemotaxis, increased expression of CCR5, and aberrant
      receptor dynamics, after RANTES stimulation as observed in SF T cells.
      CONCLUSION: Synovial fluid T cells highly positive for CCR5 show aberrant
      characteristics; resistant to RANTES in terms of migration, but responsive in
      terms of dynamics of CCR5.

PMID- 12064825
TI  - Immunoglobulin G fc-receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms related
      to disease severity in rheumatoid arthritis.
AB  - OBJECTIVE: Fc receptors for IgG (FcyR) modulate immune responses. FcyR are
      expressed on various leukocytes and contain allelic polymorphisms with different
      capacity for IgG binding and phagocytosis. We investigated the distribution of
      FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB polymorphisms in rheumatoid arthritis
      (RA) and whether they were related to disease expression and severity. METHODS:
      Ninety-six controls and 114 patients fulfilling American College of Rheumatology
      (ACR) criteria for RA were genotyped for FcgammaRIIA, IIIA, and IIIB using
      polymerase chain reaction. Physician's global assessment of RA type estimated RA
      disease expression. In addition, usual measures of disease activity were
      recorded. RESULTS: The genotype and allele frequencies did not differ
      significantly between the RA patients and the controls. Patients homo or
      heterozygous for the FcgammaRIIA arginine (R) allele had significantly more
      aggressive RA and swollen joints than patients homozygous for the FcgammaRIIA
      histidine (H) allele. Although there was a tendency of more severe disease among
      patients homo or heterozygous for the FcgammaRIIIA valine allele, there were no
      significant findings with the disease activity for the FcgammaRIIIA and
      FcgammaRIIIB genotypes. CONCLUSION: FcgammaRIIA is implicated as a possible
      disease modifying gene in RA. Individuals homozygous for the FcgammaRIIA R allele
      have less efficient binding of IgG2 subclasses than individuals homozygous for
      the H allele. Less effective processing of circulating immune complexes in RA
      patients homozygous for the FcgammaRIIA R allele may therefore contribute to a
      more unfavorable course.

PMID- 12064826
TI  - Premature immunosenescence in rheumatoid arthritis.

PMID- 12064827
TI  - The effect of health related quality of life on reported use of health care
      resources in patients with osteoarthritis and rheumatoid arthritis: a
      longitudinal analysis.
AB  - OBJECTIVE: In today's cost conscious environment, health services researchers are
      consistently trying to find ways to predict future health care resource
      utilization (HCRU) and its associated costs. We evaluated the impact of health
      related quality of life (HRQL) on future HCRU in patients with arthritis.
      METHODS: A total of 642 patients with rheumatoid arthritis (RA) and 395 patients
      with osteoarthritis (OA) completed at least 2 and as many as 6 consecutive
      surveys at 6 mo intervals. Information collected included demographics, HRQL
      questionnaires [Medical Outcome Study Short Form 36 (SF-36), Western Ontario
      McMaster Universities Osteoarthritis Index (WOMAC), and the Stanford Health
      Assessment Questionnaire (HAQ)], and HCRU over the previous 6 months.
      Longitudinal data analysis was perfomed to assess the effect of HRQL on future
      HCRU. RESULTS: Statistically significant associations between HCRU and HRQL
      variables were noted. Higher rates of HCRU were found in those in the worst
      quarter compared with those in the best quarter of HRQL. With the HAQ, OA and RA
      patients in the worst quarter reported a 199% (p < 0.05) and 48% (p < 0.05)
      increase in rheumatologist visits, respectively. With the WOMAC Function,
      increases were as high as 196% (p < 0.05) in rheumatologist visits for patients
      with OA. Patients with RA with a high level of HRQL as measured by the SF-36
      (physical component score) reported a decrease of 31% (p < 0.01) in general
      practitioner visits and a decrease of 52% (p < 0.01) in hospitalization (mental
      component score). CONCLUSION: These findings suggest that HRQL may be used to
      predict future health care consumption. Such an approach may lead to a more
      efficient allocation of resources by providing useful information to health care
      providers and health care decision makers.

PMID- 12064828
TI  - A cost effectiveness analysis of treatment options for methotrexate-naive
      rheumatoid arthritis.
AB  - OBJECTIVE: New treatment options for patients with methotrexate (MTX)-naive
      rheumatoid arthritis (RA) have become available. Given wide variability in
      efficacy and cost among different treatment options, we sought to determine their
      relative cost effectiveness to help guide policy in different cost constrained
      settings. METHODS: We performed a cost effectiveness analysis comparing 5
      monotherapy options for patients with MTX-naive RA: (1) etanercept, (2)
      leflunomide, (3) MTX (up to 15 mg weekly), (4) sulfasalazine (SSZ), and (5) no
      second line agent. A decision analysis model was used with a time horizon of 6
      months. We employed 2 measures of effectiveness based on published clinical trial
      data: American College of Rheumatology (ACR) 20% response proportion (ACR 20) and
      a weighted average of proportions achieving ACR 70, ACR 50, and ACR 20 (ACR 70
      weighted response, ACR 70WR). Incremental cost effectiveness ratios were
      calculated as additional cost per patient achieving either outcome, compared with
      the next most expensive option. RESULTS: In both base case analyses employing ACR
      20 and ACR 70WR as effectiveness measures, MTX and SSZ both cost less and were
      more effective (i.e., cost saving) than no second line agent. Leflunomide cost
      more and was less efficacious than SSZ (dominated) in analyses using either
      outcome. The most efficacious option, etanercept, cost US $41,900 per ACR 20 and
      $40,800 per ACR 70 WR compared with SSZ and MTX, respectively. When we included
      only direct costs in analyses, the least expensive non-dominated option was SSZ
      with incremental cost effectiveness ratios of US $900 per ACR 20 and $1500 per
      ACR 70WR compared with no second line agent. Overall, relative cost effectiveness
      between MTX and SSZ was sensitive to variation in relevant variables in
      sensitivity analyses. Otherwise, our extensive sensitivity analyses did not
      substantially affect the base case results. CONCLUSION: MTX is cost effective
      (cost saving vs the no second line agent option) for MTX-naive RA in achieving
      ACR 20 or ACR 70WR over a 6 month period. Based on available data, the relative
      cost effectiveness between SSZ and MTX cannot be determined with reasonable
      certainty and SSZ therapy appears to be as cost effective as MTX (cost saving) in
      achieving ACR outcomes over a 6 month period. The most efficacious option,
      etanercept, incurs much higher incremental costs per ACR 20 or ACR 70WR than
      other options analyzed. Whether etanercept compared with MTX is cost effective
      depends on whether > $40,000 per ACR 20 or ACR 70WR over a 6 month period is
      considered acceptable.

PMID- 12064829
TI  - Prevalence of rheumatoid arthritis in Tucuman, Argentina.
AB  - OBJECTIVE: To ascertain the prevalence of rheumatoid arthritis (RA) in Tucuman,
      Argentina. METHODS: The study was conducted between January 1, 1998, and December
      31, 1999, in Tucuman province in northwest Argentina. Outpatient and
      hospitalization medical records for all patients with RA aged > or = 16 years
      were reviewed. Diagnosis was by 1987 American College of Rheumatology (ACR)
      criteria for RA and the population data were based on the 1991 national census.
      Prevalence rates, with 95% CI, were calculated using the number of San Miguel de
      Tucuman residents who fulfilled the 1987 ACR criteria for RA as numerator, and
      the city population aged > or = 16 as denominator. Crude and age-specific
      prevalence rates were calculated as number of cases/1,000 inhabitants. RESULTS:
      We identified 695 cases of RA. Sex-specific and overall prevalence rates (per
      1,000) were 1.97 (95% CI 1.8-2) for all, 0.6 (95% CI 0.49-0.73) for men, 3.2 (95%
      CI 2.9-3.5) for women. CONCLUSION: Prevalence of RA is low in residents of
      Tucuman, Argentina, and comparable with rates observed in epidemiological surveys
      from Southern European countries.

PMID- 12064830
TI  - Treatment of chronic knee synovitis with arthroscopic synovectomy: longterm
      results.
AB  - OBJECTIVE: We examined the longterm results of arthroscopic synovectomy in
      chronic knee synovitis of rheumatoid arthritis (RA). METHODS: Forty-one knees of
      38 patients (30 women, 8 men), mean age of 42.7 +/- 15.3 years, were evaluated
      clinically and radiographically at a mean 8.9 years (range 5.0-12.3) after
      arthroscopic synovectomy. Arthroscopic synovectomies were always performed with a
      shaver by the same physician after failure of at least one radioactive or
      chemical synovectomy. Radiographs were blindly read by 2 examiners. RESULTS: At
      the final evaluation, the clinical results (pain, range of motion, recurrent
      effusion) were good in 29 cases (70.7%) and poor in 12 cases (knee arthroplasty
      was required in 11 cases). Radiographs highlighted significant progression of
      joint damage (more than one Larsen score grade) in 16 knees (39.0%). No
      radiographically detectable change was observed in 12 cases (29.3%), and 11 knees
      (26.8%) had a change of only one Larsen score grade. There was a close
      correlation between the Larsen score at final examination and both Larsen score
      and arthroscopic score for cartilage damage at baseline. Only 4 knees (22%) with
      grade 0 or I on preoperative radiographs had significant progression of joint
      damage, compared to 12 knees (57%) with Larsen scores of 2 or 3 at baseline.
      CONCLUSION: These data suggest that arthroscopic synovectomy is a useful
      alternative treatment for chronic knee synovitis in RA after failure of radiation
      or chemosynovectomy, and that less severely damaged joints deteriorate less
      rapidly after synovectomy.

PMID- 12064832
TI  - A functional polymorphism in fas (CD95/APO-1) gene promoter associated with
      systemic lupus erythematosus.
AB  - OBJECTIVE: To investigate whether Fas promoter polymorphisms show a genetic
      contribution to the development of systemic lupus erythematosus (SLE) in a
      Japanese population, and to study the functional difference in promoter activity
      of the polymorphisms. METHODS: In 109 SLE patients and 140 controls, the
      frequencies of A/G polymorphisms at -670 nucleotide position and G/A at -1377
      nucleotide position were determined by allele-specific polymerase chain reaction
      (PCR) or PCR-single strand conformation polymorphism analysis. The functional
      significance of the -670A/G polymorphism in the Fas gene was evaluated by a
      combination of Fas transcriptional activity in the reporter gene assay and
      binding activity of signal transducer and activator of transcription (STAT) 1
      protein in the electrophoretic mobility shift assay. RESULTS: SLE patients
      exhibited significantly higher frequency of A allele at nucleotide position -670
      (p = 0.004). There was no significant difference in the nucleotide position -1377
      in Fas promoter gene between SLE patients and controls. The electrophoretic
      mobility shift assay demonstrated that the oligonucleotide with -670A in the Fas
      promoter had a higher binding ability to a GAS binding protein, STAT1, than that
      with -670G, although there was no statistically significant difference in the
      reporter gene assay. CONCLUSION: Fas promoter -670A/G polymorphism was
      significantly associated with SLE, suggesting a possibility that Fas promoter
      contributes, at least in part, to the pathogenesis of SLE.

PMID- 12064831
TI  - Antigen induced arthritis (AIA) can be transferred by bone marrow
      transplantation: evidence that interleukin 6 is essential for induction of AIA.
AB  - OBJECTIVE: To investigate the role of bone marrow cells (BMC) in the induction of
      antigen induced arthritis (AIA), the expression of 3 major proinflammatory
      cytokines, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha),
      and IL-6, was examined in the bone marrow (BM) of mice with AIA. We also examined
      whether AIA could be transferred by bone marrow transplantation (BMT). METHODS:
      Expression of IL-1beta, TNF-alpha, and IL-6 in BMC was assessed by
      immunohistochemistry throughout the course of AIA. BMT experiments were performed
      using 2 different mouse genotypes, wild type (IL-6+/+) and IL-6 deficient (IL-6-/
      ) mice, as a donor. The gradation of AIA was evaluated histologically. RESULTS:
      IL-6 was highly expressed in the BM at induction as well as during progression of
      AIA, while TNF-alpha showed a marginal expression, and no significant expression
      of IL-1beta was detected throughout the course of AIA. In BMT experiments, all
      irradiated IL-6+/+ mice developed typical AIA by transplantation of BMC from
      immunized IL-6+/+ mice, whereas almost no irradiated IL- 6+/+ mice transplanted
      with BMC from the immunized IL-6-/- mice developed definite arthritis.
      CONCLUSION: These results suggest that BMC play a critical role and IL-6 is a key
      cytokine for the induction and progression of AIA. There may be clinical benefits
      in the blockade of IL-6 and BMT in the treatment of rheumatoid arthritis.

PMID- 12064833
TI  - Transforming growth factor-12 polymorphism and systemic lupus erythematosus.
AB  - OBJECTIVE: To determine whether transforming growth factor-beta2 (TGF-beta2) gene
      polymorphism is associated with systemic lupus erythematosus (SLE)
      susceptibility. TGF-beta is a multifunctional family of cytokines important in
      tissue repair, inflammation and immunoregulation. SLE is thought to be a T cell
      dependent autoimmune disorder with T cell dysfunction. Due to its known
      suppressive effects on interleukin 2 dependent T cell growth, TGF-beta2 is
      considered to be a candidate SLE susceptibility gene. Furthermore, SLE has been
      linked with a region to which the TGF-beta2 gene has been mapped. METHODS:
      Association studies were performed in 3 case-control populations, from Spain.
      Turkey, and UK, using a TGF-beta2 5'-untranslated region (5'-UTR) 4 base pair
      (bp) insertion polymorphism. Genotyping was performed using fluorescent labeled
      polymerase chain reaction product sizing. Results. No significant differences
      were detected in TGF-beta2 5'-UTR polymorphism allele frequencies between SLE
      patients and matched controls in the 3 populations studied. CONCLUSION: The 4 bp
      insertion polymorphism within the TGF-beta2 gene does not appear to be associated
      with SLE. However, this does not rule out the possible involvement of TGF-beta2
      in the disease pathogenesis.

PMID- 12064834
TI  - Gene polymorphisms of tissue plasminogen activator and plasminogen activator
      inhibitor-1 in patients with antiphospholipid antibodies.
AB  - OBJECTIVE: Impaired fibrinolytical outcomes may be one of the pathogenic factors
      for thrombotic events in patients with antiphospholipid antibodies (aPL). We
      investigated the consequences of the gene polymorphisms of tissue plasminogen
      activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) in patients
      positive for aPL. METHODS: Seventy-seven Japanese and 82 British patients with
      aPL were examined for Alu-repeat insertion (I)/deletion (D) polymorphism of the
      tPA gene by polymerase chain reaction (PCR), and 4G/5G polymorphism in the PAI-1
      promoter gene by site-directed mutagenesis-PCR and restriction fragment length
      polymorphism analysis. Correlations between these polymorphisms and clinical
      symptoms of antiphospholipid syndrome (APS) (arterial thrombosis, venous
      thrombosis, miscarriage) were analyzed. RESULTS: Significant differences in the
      allele frequencies of these genes did not exist between patients and controls.
      There was no significant correlation between these gene polymorphisms and
      clinical symptoms of APS in patients with aPL. CONCLUSION: Polymorphisms of the
      tPA or PAI-1 genes probably do not significantly influence the risk of anerial
      thrombosis, venous thrombosis, or pregnancy morbidity in patients with aPL.

PMID- 12064835
TI  - Hospital experience and mortality in patients with systemic lupus erythematosus:
      which patients benefit most from treatment at highly experienced hospitals?
AB  - OBJECTIVE: To determine if hospitalization at a hospital experienced in the
      treatment of systemic lupus erythematosus (SLE), compared to hospitalization at a
      less experienced hospital, is associated with decreased in-hospital mortality in
      all subsets of patients with SLE, or if the decrease in mortality is greater for
      patients with particular demographic characteristics, manifestations of SLE, or
      reasons for hospitalization. METHODS: Data on in-hospital mortality were
      available for 9989 patients with SLE hospitalized in acute care hospitals in
      California from 1991 to 1994. Differences in in-hospital mortality between
      patients hospitalized at highly experienced hospitals (those hospitals with more
      than 50 urgent or emergent hospitalizations of patients with SLE per year) and
      those hospitalized at less experienced hospitals were compared in patient
      subgroups defined by age, sex, ethnicity, type of medical insurance, the presence
      of common SLE manifestations, and each of the 10 most common principal reasons
      for hospitalization. RESULTS: In univariate analyses, in-hospital mortality was
      lower among those hospitalized at a highly experienced hospital for women,
      blacks, and Hispanics, and those with public medical insurance or no insurance.
      The risk of in-hospital mortality was similar between highly experienced and less
      experienced hospitals for men, whites, and those with private insurance. Patients
      with nephritis also had lower risks of in-hospital mortality if they were
      hospitalized at highly experienced hospitals, but this risk did not differ in
      subgroups with other SLE manifestations or subgroups with different principal
      reasons for hospitalization. In multivariate analyses, only the interaction
      between medical insurance and hospitalization at a highly experienced hospital
      was significant. Results were similar in the subgroup of patients with an
      emergency hospitalization (n = 2,372), but more consistent benefits of
      hospitalization at a highly experienced hospital were found across subgroups of
      patients with an emergency hospitalization due to SLE (n = 405). CONCLUSION:
      Risks of in-hospital mortality for patients with SLE were similar between highly
      experienced hospitals and less experienced hospitals for patients with private
      medical insurance, but patients without private insurance had much lower risks of
      mortality if hospitalized at highly experienced hospitals. The benefit of
      hospitalization at highly experienced hospitals was more consistent across
      subgroups of patients with a hospitalization due to SLE, suggesting that
      differences specifically in the treatment of SLE, rather than differences in the
      general quality of medical care, account for the lower mortality among patients
      with SLE hospitalized at highly experienced hospitals.

PMID- 12064836
TI  - Role of specialty care in the management of patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the role of rheumatologists in the management of systemic
      lupus erythematosus (SLE). METHODS: The lupus clinic database was searched for
      patients with 3 consecutive visits (every 3-4 months) of which the first 2 visits
      recorded a SLE Disease Activity Index (SLEDAI) of 0. The clinic notes were
      examined by a physician blinded to the SLEDAI score at the third visit. The
      physician classified the rheumatologist's action by the following scale: 1 = no
      change, 2 = closer followup, 3 = new investigations, 4 = increase medications, 5
      = lower medications. All interventions (2-5) were further scored as being related
      to or independent of SLE. RESULTS: Of the 142 SLE patients identified, 70
      patients remained inactive (SLEDAI = 0) and 72 patients experienced flare (SLEDAI
      > 0) at the third visit. In total, 74% of patients, regardless of the status of
      disease activity, required intervention; 96% of interventions in patients with
      clinical flare, 72% with serological flare, and 63% with inactive disease were
      due to management of SLE. The most frequent intervention related to SLE in
      patients with clinical flare was increasing medication, while in inactive SLE
      lowering medication was the most common intervention. CONCLUSION: Even after a
      period of relative disease quiescence the majority of patients with lupus require
      active intervention during a subsequent routine clinic visit. Most interventions
      are related to the management of SLE. Therefore ongoing monitoring by
      rheumatologists in the management of lupus seems prudent.

PMID- 12064837
TI  - No association of vitamin D receptor gene start codon fok 1 polymorphisms in
      Chinese patients with systemic lupus erythematosus.
AB  - OBJECTIVE: To examine whether the start codon Fok I of the vitamin D receptor
      (VDR) gene polymorphism is a marker of susceptibility to or severity of systemic
      lupus erythematosus (SLE) in Chinese patients in Taiwan. METHODS: A control group
      of 90 healthy people and 52 patients with SLE were examined. Using polymerase
      chain reaction (PCR) based restriction analysis, we evaluated the relationship
      between Fok I polymorphisms and SLE, where an unexcisable length was determined
      to be 265 bp (FF), and the 2 fragments measuring 169 bp and 96 bp were determined
      to be excisable lengths (ff). RESULTS: For the genotype of VDR Fok I start codon
      polymorphism, there were no statistically significant differences between the 2
      groups (chi-squared test, p = 0.07). Additionally, we did not detect any
      association of VDR genotype with the clinical and laboratory profiles in SLE
      patients. CONCLUSION: Our results suggest that the vitamin D receptor Fok I start
      codon polymorphism is not related to patients with SLE in Taiwan.

PMID- 12064838
TI  - Risk factors of mortality for salmonella infection in systemic lupus
      erythematosus.
AB  - OBJECT: To investigate the risk factors of mortality for Salmonella infection in
      patients with systemic lupus erythematosus (SLE). METHODS: Between 1995 and 1999
      we reviewed 37 cases of Salmonella infection in 31 patients with SLE from a total
      of 1191 hospitalized patients with SLE at a medical center in Taiwan. Contrasting
      cases of patients who died with those who survived, we compared clinical and
      laboratory characteristics of SLE at the time of Salmonella infection, with
      special attention to potential risk factors (sex, age, complete blood count and
      differential count, erythrocyte sedimentation rate, C-reactive protein,
      complements, Salmonella species, infection site, reinfection, SLE presenting with
      Salmonella infection, associated non-Salmonella infection, etc.). RESULTS: The
      mean age at the onset of SLE in the 8 mortality cases was significantly higher
      than the 23 cases of survivors (p < 0.05). Other factors significantly related to
      death included associated infections other than Salmonella species, reinfection
      of Salmonella species, and cases of SLE presenting with Salmonella infection.
      Reinfection and SLE presenting with Salmonella infection were the most important
      risk factors of mortality for SLE with Salmonella infections: relative risk (CI)
      84 (4.3-1638.8) and 63 (3.1-1296.5), respectively. CONCLUSION: Patients with SLE
      who are older or have associated infections other than Salmonella have an
      increased mortality rate when they have concurrent Salmonella infection. Patients
      with Salmonella infection occurring concurrently with the first presentation of
      SLE and patients with SLE reinfected with Salmonella species are at higher risk
      of mortality.

PMID- 12064839
TI  - Sex differences in giant cell arteritis.
AB  - OBJECTIVE: Although it has been suggested that sex differences underlie the
      varying presentation of giant cell arteritis (GCA), this has not been proven. We
      compared medical history, symptoms, and signs in patients with GCA and
      polymyalgia rheumatica (PMR). METHODS: We performed a retrospective study in the
      Hadassah University Hospitals in Jerusalem, Israel. We evaluated medical data of
      88 patients (59 women, 29 men) admitted with the diagnosis of GCA or PMR between
      1980 and 1998. RESULTS: Comparison of comorbidities among patients showed that
      non-insulin dependent diabetes mellitus, cerebrovascular accidents, and chronic
      renal failure are more prevalent in men, while hypertension has a trend to be
      more prevalent in women. In the clinical presentation of the disease, eye
      involvement is more prevalent in men, with a tendency towards blindness. Women
      tend to have higher prevalence of jaw involvement and complaints of polymyalgia.
      The sexes also seem to differ with respect to laboratory presentation of the
      disease. CONCLUSION: Men and women with GCA and PMR differ in their history,
      presentation, and laboratory findings. Our results recommend a more aggressive
      approach to male patients in view of the higher prevalence of severe eye
      involvement and blindness.

PMID- 12064840
TI  - The predictive value of the halo sign in color Doppler ultrasonography of the
      temporal arteries for diagnosing giant cell arteritis.
AB  - OBJECTIVE: The diagnosis of giant cell arteritis (GCA) usually requires a
      temporal artery biopsy. Recently it has been reported that a periluminal dark
      halo, detected by color Doppler ultrasonography (US) of the temporal arteries, is
      a characteristic sign of GCA. We evaluated the predictive value of this dark halo
      sign in diagnosing GCA. METHODS: During a period of 2 years 69 patients suspected
      of having GCA were examined by US of both temporal arteries. Temporal artery
      biopsy was performed in 32 of these patients. The diagnosis of GCA was made if a
      patient had a biopsy showing arteritis, or met all the following criteria: (1)
      American College of Rheumatology GCA classification criteria were fulfilled; (2)
      there was a prompt clinical response to treatment with 40-60 mg/day of
      prednisone; and (3) no other diagnosis related to the patient's symptoms was made
      during 6 month followup. RESULTS: Periluminal dark halo was observed in 24 of 69
      patients. GCA was diagnosed in 12 of them, giving a positive predictive value
      (PPV) of only 50%. No halo was detected in 45 cases of which only 2 had GCA,
      resulting in a high negative predictive value (NPV) of 96%. The sensitivity and
      specificity of the halo sign for diagnosing GCA were 86% and 78%, respectively.
      CONCLUSION: The PPV of the halo sign in US of the temporal arteries is
      unsatisfactory for diagnosing GCA. However, the NPV is very high. Thus the lack
      of a halo can practically serve to rule out a diagnosis of GCA, and precludes the
      need for a biopsy in most instances.

PMID- 12064841
TI  - Parvoviral infection of endothelial cells and its possible role in vasculitis and
      autoimmune diseases.
AB  - OBJECTIVE: To analyze a series of biopsies from 16 patients who, on the basis of
      clinical and dermatopathologic findings, had a spectrum of connective tissue
      diseases (CTD), autoinflammatory or CTD-like syndromes for parvoviral DNA, RNA,
      and protein. METHODS: Most of the patients were initially screened for parvoviral
      related IgG and IgM antibodies. Parvoviral DNA was analyzed by solution phase
      polymerase chain reaction (PCR). In situ localization of viral VP1 RNA was
      accomplished by in situ reverse transcriptase (RT) PCR; viral protein (VP2) was
      detected by immunohistochemistry and these results correlated with the histologic
      findings. (J Rheumatol 2002;29:xxxx) RESULTS: Of 11 people tested, 10 had either
      IgG or IgM specific antibodies against parvovirus. Common histologic features of
      the 16 cases included an interface dermatitis, interstitial histiocytic
      infiltration with variable collagen necrobiosis, a mononuclear cell dominant
      vasculitis, and interstitial neutrophilia. Detection of parvoviral RNA by in situ
      RT-PCR in 14 of 16 cases corroborated solution phase PCR data and demonstrated
      that the endothelial cells and surrounding mononuclear cells were the viral
      target. Viral protein as revealed by immunohistochemisty showed an equivalent
      histologic distribution. Anti-tumor necrosis factor-alpha (TNF-alpha) therapy
      (etanercept) yielded dramatic improvement after worsening of symptoms with
      traditional immunosuppressive therapy in the 3 patients in whom this drug was
      administered; TNF-alpha mRNA was detected by in situ RT-PCR in the area of
      parvoviral infected cells. CONCLUSION: Parvoviral induced endothelialitis may be
      responsible for cases of "idiopathic" CTD.

PMID- 12064843
TI  - Accelerated alveolar bone loss in HLA-b27 transgenic rats: an adult onset
      condition.
AB  - OBJECTIVE: Patients with arthritis and Crohn's disease may be more susceptible to
      periodontitis associated alveolar bone loss (ABL). HLA-B27 transgenic (TG) rats
      spontaneously develop arthritis and colitis. Based on the hypothesis that TG rats
      would also be susceptible to ABL, we compared the naturally occurring ABL in TG
      and Fischer 344 wild-type (WT) rats. METHODS: Eighteen TG and 18 WT virgin female
      rats were used. Pairs (I TG, I WT) were housed in suspended wire cages. At age
      2.6, 6, and 11 months, 8, 5, and 5 pairs were sacrificed, respectively. ABL was
      measured as exposed molar root surface area (mm2). Western blotting was used for
      analysis of serum reactivity against bacteria associated with arthritis, colitis,
      and periodontitis development. RESULTS: At 2.6 months of age, there was no
      difference in ABL between TG and WT rats. At 6 and 11 months ABL was
      significantly greater in TG animals by 28% and 53%, respectively. For TG rats,
      ABL was significantly different between the 3 age groups. For WT rats, ABL was
      not significantly different between 6 and 11 months. Western blotting revealed
      distinct TG serum reactivity against extracts of Bacteroides vulgatus, B.
      fragilis, Prevotella intermedia, and to a lesser extent against extracts of B.
      forsythus. CONCLUSION: The accelerated ABL in HLA-B27 TG rats is an adult onset
      condition, independent of husbandry conditions or parity status. HLA-B27 rats
      exhibit strong immunoreactivity against bacteria implicated in arthritis,
      colitis, and periodontitis.

PMID- 12064842
TI  - The natural history of ankylosing spondylitis as defined by radiological
      progression.
AB  - OBJECTIVE: Radiological status is an important objective endpoint in the
      assessment of ankylosing spondylitis (AS). We investigated the disease
      development of AS using radiological change. METHODS: The existing radiographs (n
      = 2,284) of 571 AS patients attending the Royal National Hospital for Rheumatic
      Diseases were scored retrospectively using the Bath Ankylosing Spondylitis
      Radiology Index. (1) Progression of disease was initially examined cross
      sectionally. Univariate analysis was used to examine factors associated with
      joint involvement. (2) Progression of disease was then examined longitudinally
      for patients with films at time of symptom onset. (3) Rate of progression of
      radiological change was calculated using longitudinal data of 2 sets of
      radiographs taken 10 years apart (patient number = 54). The results from this
      were used to extrapolate backwards to age at first radiological change. RESULTS:
      (1) Progression to cervical spine disease was a function of: disease duration,
      severity of hip and lumbar involvement, and a history of iritis (p < 0.001).
      Lumbar involvement was associated with disease duration, age now, and severity of
      cervical and hip involvement (p < 0.001). Hip involvement was a marker for
      cervical disease and associated with disease duration (p < 0.001). (2)
      Longitudinal analysis revealed marked variation among patients with a slow
      general rate of progression. (3) The progression of AS over any 10 year period is
      linear [first 10 years = 30% (SD 0.3) of potential change, 10-20 yrs = 40% (SD
      0.3) change, 20-30 yrs = 35% (SD 0.4) change (p = 0.5)]. Backward extrapolation
      suggests that the approximate time of first radiological change is at the age of
      8 years. CONCLUSION. (1) AS is a linearly progressive disease with about 35%
      change every 10 years. Spinal involvement is largely an expression of disease
      duration while the hips become involved in about 25% of individuals and may
      predict a more severe outcome for the cervical spine. (2) Backward extrapolation
      shows that the disease process may start as young as 8 years of age. However, the
      time interval between the disease trigger and radiological change remains
      unknown.

PMID- 12064844
TI  - Corticotropin releasing hormone (CRH) antagonist attenuates adjuvant induced
      arthritis: role of CRH in peripheral inflammation.
AB  - OBJECTIVE: To determine whether a corticotropin releasing hormone (CRH) type 1
      specific receptor antagonist, antalarmin, would alter the progression of
      inflammation in adjuvant induced arthritis (AIA) susceptible LEW/N rats by
      blocking local CRH mediated inflammatory responses or render AIA resistant F344/N
      rats more susceptible to AIA by blocking central CRH, thus reducing secretion of
      endogenous glucocorticoids. METHODS: F344/N and LEW/N rats were assigned to
      either drug or vehicle groups and treated with 20 mg/kg antalarmin or vehicle
      alone BID for 25 days by intraperitoneal injection. Arthritis was induced in both
      antalarmin and vehicle treated LEW/N and F344/N rats by subcutaneous injections
      at the base of the tail of incomplete Freund's adjuvant containing 10 mg/ml heat
      killed Mycobacterium tuberculosis. Control F344/N and LEW/N rats were maintained
      on either antalarmin or vehicle. RESULTS: Chronic blockade of CRH-R1 with
      systemic antalarmin significantly ameliorated AIA in LEW/N rats, reducing the
      severity of inflammation in peripheral joints, evidenced by clinical and
      histopathology scores, and weight loss associated with disease onset. Antalarmin
      neither induced nor exacerbated arthritis expression in F344/N or LEW/N rats,
      despite suppression of levels of adjuvant induced corticosterone, the major
      antiinflammatory glucocorticoid in rats. CONCLUSION: Systemic blockade of CRH-RI
      appeared to predominantly block peripheral proinflammatory effects of immune CRH,
      rather than the systemic glucocorticoid mediated antiinflammatory effects of
      hypothalamic CRH. Results indicate that chronic treatment with a CRH antagonist
      attenuates progressive inflammation induced degeneration of synovia, cartilage,
      and bone in arthritic joints, suggesting that antalarmin may have therapeutic
      potential in treatment of human autoimmune and inflammatory disorders.

PMID- 12064845
TI  - Interleukin 17 (IL-17) induces collagenase-3 production in human osteoarthritic
      chondrocytes via AP-1 dependent activation: differential activation of AP-1
      members by IL-17 and IL-1beta.
AB  - OBJECTIVE: In osteoarthritic (OA) synovial fluid, many proinflammatory cytokines
      coexist and stimulate chondrocytes. As interleukin 17 (IL-17) is a catabolic
      cytokine, we explored its effects on collagenase-3 production. In a comparative
      manner we identified IL-17 and IL-1beta induced transcription factors mediating
      upregulation of this enzyme's production. METHODS: Collagenase-3 levels were
      determined by ELISA. Transfection experiments of human OA chondrocytes were
      performed, with the plasmids -1599CAT and -133CAT consisting of 1.6 kb and the
      first proximal 133 bp containing polyomavirus enhancer A-3 (PEA-3), activating
      protein-1 (AP-1), and TATA box of the human collagenase-3 promoter, respectively.
      Electrophoretic mobility shift assays were done with the AP-1 and PEA-3
      oligonucleotides derived from the human collagenase-3 promoter sequence.
      Supershift assays were carried out with the specific antibodies against the Jun
      and Fos proteins. RESULTS: IL-17 induced collagenase-3 expression and synthesis,
      with an EC50 at 10 ng/ml. Transfection experiments with wild-type -1599CAT and 
      133CAT and their mutated AP-1 or PEA-3 derivatives revealed that the AP-1 site
      was essential for basal and proinflammatory cytokine induced collagenase-3
      promoter activity, whereas the PEA-3 motif exerted a cooperative effect. Of note,
      in OA chondrocytes, IL-17 and IL-1beta induced collagenase-3 production through
      AP-1 occurred with differential protein complexes: IL-17 stimulation resulted in
      FosB activation, while IL-1beta stimulated c-Fos. Data showed a strong activation
      of JunB only in cells showing a higher collagenase-3 basal level and low cytokine
      (IL-17 and IL-1beta) inducibility, suggesting this transcription factor protein
      acts as a negative regulator. CONCLUSION: We demonstrated that IL-17 and IL-1beta
      induced collagenase-3 production in OA chondrocytes mainly through AP-1 mediated
      transcriptional activity but with differential protein complexes, suggesting that
      some AP-1 proteins play a pivotal role in the different cytokine responses in
      terms of collagenase-3 production. Our data might suggest that JunB protein plays
      a rate-limiting step in cytokine induced collagenase-3 production in OA
      chondrocytes.

PMID- 12064846
TI  - The importance of patient expectations in predicting functional outcomes after
      total joint arthroplasty.
AB  - OBJECTIVE: To evaluate the relationship between patient expectations of total
      joint arthroplasty (TJA) and health related quality of life plus satisfaction 6
      months after surgery. Methods. This prospective cohort study included patients
      undergoing primary total hip (THA) and knee arthroplasty (TKA). Patients were
      evaluated with self-report questionnaires prior to surgery and 6 months post
      surgery. Medical Outcomes Study Short Form 36 (SF-36), the Western Ontario
      McMaster Universities Osteoarthritis Index (WOMAC), and a satisfaction scale were
      used to evaluate outcomes at final followup. Multivariate regression models were
      used to evaluate the impact of expectations on outcomes. RESULTS: There were 102
      patients with THA and 89 with TKA. Mean age was 66 years. All patients achieved
      significant improvements in their WOMAC and SF-36 scores following surgery.
      Patient expectations regarding surgery were not associated with their age,
      gender, index joint of surgery, marital status, or race. Expectations were not
      correlated with pre-operative functional health status. Expectation of complete
      pain relief after surgery was an independent predictor of better physical
      function and improvement in level of pain at 6 months post-surgery. Expectation
      of low risk of complications from TJA was an independent predictor of greater
      satisfaction. CONCLUSIONS: Patient expectations were important independent
      predictors of improved functional outcomes and satisfaction following TJA.
      Greater understanding of the relationship between expectations and outcomes may
      improve the process of care and outcomes of TJA.

PMID- 12064847
TI  - Improving physical functional status in patients with fibromyalgia: a brief
      cognitive behavioral intervention.
AB  - OBJECTIVE: Sustained improvement in physical functional status was the primary
      goal of a brief, 6 session cognitive behavioral therapy (CBT) protocol for
      fibromyalgia (FM). METHODS: One hundred forty-five patients with FM were randomly
      assigned to either (1) standard medical care that included pharmacological
      management of symptoms and suggestions for aerobic fitness, or (2) the same
      standard medical treatment plus 6 sessions of CBT aimed at improving physical
      functioning. Outcome measures included the Medical Outcome Study Short Form-36
      Physical Component Score and McGill ratings of pain. Outcomes were treated
      dichotomously using a preestablished criterion for clinically significant success
      based upon the reliability of change index from baseline to one year
      posttreatment. RESULTS: Twenty-five percent of the patients receiving CBT were
      able to achieve clinically meaningful levels of longterm improvement in physical
      functioning, whereas only 12% of the patients receiving standard care achieved
      the same level of improvement. There were no lasting differences on pain ratings
      between groups. CONCLUSION: Lasting improvements in physical functioning have
      been among the most difficult outcomes to obtain in studies of FM. These data
      suggest that the inclusion of CBT to a standard medical regimen for FM can
      favorably influence physical functioning in a subset of patients.

PMID- 12064849
TI  - Linear growth and final height in patients with systemic juvenile idiopathic
      arthritis treated with longterm glucocorticoids.
AB  - OBJECTIVE: To assess linear growth and final height in patients given
      glucocorticoids during childhood for systemic juvenile idiopathic arthritis
      (JIA). METHODS: Heights throughout followup for JIA and final height were
      recorded in 24 patients. Height data were expressed as the height standard
      deviation score for chronological age (HSDS/CA). Final height was compared to
      reference values for the French population and to target height. RESULTS: During
      glucocorticoid therapy, mean loss of HSDS/CA was -2.7 +/- 1.5 and was positively
      correlated with prednisone therapy duration (p < 0.01). After prednisone
      discontinuation, 17 patients (70%) had catch-up growth and 7 (30%) continued to
      experience slow linear growth. Mean final height was -2.0 +/- 1.8 HSDS and was
      correlated with mean height at prednisone discontinuation (p < 0.0001). Mean
      final height was significantly greater in the patients with catch-up growth at
      prednisone discontinuation (-1.5 +/- 1.6 vs -3.6 +/- 1.2 HSDS), and 87% of
      patients had a final height below their target height. CONCLUSION: These data
      suggest that chronic inflammation and prednisone therapy may adversely affect
      growth in patients with JIA, and that final height may be closely dependent both
      on the severity of growth retardation during the active phase of the disease and
      on linear growth after remission. Thus treatments like growth hormone presently
      under investigation to improve final height may be most effective when given
      early after disease onset and/or at remission.

PMID- 12064848
TI  - Effects of strength training on muscle strength, cross-sectional area, maximal
      electromyographic activity, and serum hormones in premenopausal women with
      fibromyalgia.
AB  - OBJECTIVE: To examine the effects of strength training on basal concentrations
      and acute responses of serum hormones, and their possible interrelationships with
      training induced muscle hypertrophy and strength gains of the knee extensor
      muscles in women with fibromyalgia (FM) and healthy controls. METHODS: Twenty-one
      premenopausal women with FM were randomized to 21 week strength training (FMT; n
      = 11) or control (FMC; n = 10) groups. Twelve premenopausal sedentary healthy
      women served as controls (HC). Surface electromyographic (EMG) activity, maximal
      unilateral isometric force of the right knee extensors, and muscle cross
      sectional area (CSA) of the quadriceps femoris throughout the lengths of 3/12 to
      12/15 of the femur (Lf) were measured. Serum concentrations of total and free
      testosterone and growth hormone (GH) were analyzed at rest and in pre- and post
      exercise conditions, while levels of insulin-like growth factor and
      dehydroepiandrosterone sulfate were measured at rest only. RESULTS: Mean (SD)
      maximal force increased by 18% (10%) (p < 0.001) in the FMT group, and by 22%
      (12%) (p < 0.001) in the HC, while in the FMC it remained unchanged. Maximum
      integrated EMG of the agonists (VL + VM/2) increased in HC by 22% (p < 0.05) and
      in the FMT by 19% (p < 0.05). Significant increases in the CSA of the QF were
      observed at 5 to 12/15 Lf in FMT (p < 0.05-0.01) and at 3 to 12/15 Lf in HC (p <
      0.05-0.001), while in FMC the CSA remained unchanged. No training induced changes
      occurred in the basal concentrations of serum hormones examined. A significant
      acute increase took place in the mean concentration of GH at pre-training in HC
      (p < 0.01) and in the FMT (p < 0.05), while at post-training the elevations after
      the loading (p < 0.001 and 0.05) remained elevated up to 15 min (p < 0.05) in HC
      and up to 30 min (p < 0.01) post-loading in the FMT. CONCLUSION: Both the
      magnitude and time course of adaptations of the neuromuscular system to
      resistance training in women with FM were completely comparable to those taking
      place in healthy women. Basal levels of the anabolic hormones seem to be similar
      in women with FM compared to age matched healthy women. Observations recorded
      during the acute loading conditions might be considered an indication of the
      training induced adaptation of the endocrine system, showing that the acute GH
      response may become systematic after strength training in both women with FM and
      controls.

PMID- 12064850
TI  - Immunohistological analysis of CD59 and membrane attack complex of complement in
      muscle in juvenile dermatomyositis.
AB  - OBJECTIVE: To assess the presence of CD59 and the deposition of membrane attack
      complex (MAC) of complement system in skeletal muscle from patients with juvenile
      dermatomyositis (JDM), in comparison to patients with muscular dystrophies (MD)
      and children with normal muscle biopsies. METHODS: Muscle specimens obtained for
      diagnostic purposes from 10 patients with JDM, 6 with MD, and 7 children whose
      biopsies showed normal histology were analyzed. Immunohistological staining was
      performed using Mab against CD59 (YTH 53.1) and MAC (WU 7.2). RESULTS:
      Immunohistochemical staining for CD59 was weak and irregularly distributed on
      muscle fibers of all patients with JDM. Two of the 9 biopsies that allowed
      analysis of vessels showed negative CD59 staining in all vessels; in the
      remaining 7 patients, there was weak staining in a proportion of the vessels. In
      contrast, uniform and strong or moderate immunoreactivity was detected on the
      sarcolemma and in intramuscular endothelium in all normal and MD samples.
      Immunostaining for MAC was strong in JDM muscle vessels, and weak in normal or MD
      muscle. An inverse relation was found between MAC deposition and presence of CD59
      in vessels in 6/9 JDM biopsies and in all normal and MD samples. CONCLUSION:
      Decreased CD59 expression in JDM muscle fibers and vessels may be associated with
      muscle lesions mediated by deposition of MAC of complement in JDM.

PMID- 12064851
TI  - Which is the best radiographic protocol for a clinical trial of a structure
      modifying drug in patients with knee osteoarthritis?

PMID- 12064852
TI  - The treatment of acute rheumatism by salicin, by T.J. Maclagan--The Lancet, 1876.

PMID- 12064853
TI  - Familial Mediterranean fever in 2 Japanese families.
AB  - We describe 3 Japanese patients in 2 families with familial Mediterranean fever
      (FMF) as determined by gene analysis. FMF is an ethnically related, genetic
      disease, occurring commonly in some Mediterranean populations. The FMF gene
      (MEFV) mutation found in our patients is M694I. The patients may be remote from
      East Asian extraction.

PMID- 12064854
TI  - Cutaneous T cell lymphoma in a patient with primary biliary cirrhosis and
      secondary Sjogren's syndrome.
AB  - We describe a patient with primary biliary cirrhosis (PBC) and secondary
      Sjogren's syndrome (SS) with pulmonary involvement who developed a cutaneous T
      cell lymphoma. The clinical course of secondary SS in PBC is thought to be less
      complicated than in progressive systemic scleroderma and SS. In contrast to
      secondary SS, the risk for developing non-Hodgkin's lymphoma is highly increased
      in patients with primary SS. Moreover, these lymphomas are usually of B cell
      origin. There are few reports of T cell lymphoma in primary SS. The occurrence of
      a T cell lymphoma in a patient with PBC and secondary SS indicates the necessity
      to investigate lymphoma in patients with secondary SS.

PMID- 12064855
TI  - Concurrent occurrence of chylothorax, chylous ascites, and protein-losing
      enteropathy in systemic lupus erythematosus.
AB  - We describe 2 patients with systemic lupus erythematosus (SLE) who presented with
      chylothorax, chylous ascites, and protein-losing enteropathy. Analysis of pleural
      or peritoneal fluid revealed a high level of triglyceride and elevated 24 h stool
      alpha1-antitrypsin clearance in keeping with protein-losing enteropathy. One
      patient failed to respond to high dose corticosteroid therapy but recovered after
      3 cycles of monthly cyclophosphamide treatment. The other patient initially
      responded to high dose corticosteroid therapy, but succumbed to infectious
      complications. This is the first report of occurrence of chylothorax and chylous
      ascites associated with SLE.

PMID- 12064857
TI  - Diagnostic usefulness of 3 dimensional gadolinium enhanced magnetic resonance
      venography in antiphospholipid syndrome.

PMID- 12064856
TI  - New onset systemic lupus erythematosus with pheochromocytoma.
AB  - We describe a patient with positive antinuclear and anti-Smith antibodies,
      proteinuria, and thrombocytopenia suggesting systemic lupus erythematosus (SLE).
      During hospitalization, the patient developed labile hypertension, tachycardia,
      and intermittent fever. A computer tomography scan of the abdomen showed an
      extraadrenal mass, which was confirmed as a pheochromocytoma. After removal of
      the pheochromocytoma, the patient's symptoms resolved and her serology
      normalized. Previous case reports describe SLE patients with adrenal
      pheochromocytomas that presented many years after the diagnosis of lupus. This is
      a novel case of pheochromocytoma discovered at the onset of SLE, with resolution
      of SLE manifestations shortly after its removal.

PMID- 12064858
TI  - Trochanteric bursitis in rheumatoid arthritis.

PMID- 12064859
TI  - Failure to detect antibodies to extracellular loop peptides of the muscarinic M3
      receptor in primary Sjogren's syndrome.

PMID- 12064860
TI  - Total hip arthroplasty in ankylosing spondylitis.

PMID- 12064861
TI  - Hemochromatosis and porphyria.
AB  - A 52-year-old man presented to his primary care physician with blisters and sores
      on the backs of his hands. Laboratory studies supported a diagnosis of porphyria
      cutanea tarda, complicated by the presence of both the C282Y and H63D mutations
      in the HFE gene, with susequent iron over-load. This case illustrates the need to
      understand the pathogenesis of porphyria cutanea tarda, particularly the role of
      excess iron in the overproduction of uroporphyrin. Iron, by catalyzing the
      formation of reactive oxygen species, can enhance uroporphyrin formation by
      increasing the rate at which uroporphyrinogen is oxidized to urophophyrin. Iron
      may also act indirectly to inhibit uroporphyrinogen decarboxylase activity by
      enhancing the formation of non-porphyrin products of porphyrinogen oxidation that
      are themselves direct inhibitors of the enzyme. Finally, iron can act to increase
      urophorphyrin production by inducing delta-aminolevulinic acid synthase, thus
      increasing the amount of delta-aminolevulinic acid, the precursor to
      uroporphyrinogen, present in the cell. After the diagnosis, the patient underwent
      an aggressive series of therapeutic phlebotomies to reduce iron levels, and
      gradually the cutaneous manifestations of porphyria cutanea tarda improved.

PMID- 12064863
TI  - Diagnosis of hemochromatosis.
AB  - Hereditary hemochromatosis is an inherited disorder of iron metabolism affecting
      approximately 1 in 200 to 300 individuals of Northern European descent. Over
      time, the continued deposition of iron in parenchymal cells of many organs can
      eventually lead to diabetes mellitus, cardiomyopathy, and hepatic cirrhosis, the
      last of which is frequently followed by hepatocellular carcinoma. Although the
      complications of hereditary hemochromatosis can be devastating, its clinical
      management is simple and effective if the disease is identified early in its
      progression. In affected individuals, it is important to confirm or exclude the
      presence of cirrhosis and begin therapy as early as possible. The insidious onset
      and high prevalence of nonspecific symptoms in the early stages of the disease
      requires the clinician to have a high index of clinical suspicion for this
      disease. This is particularly important because treatment before there is
      permanent organ damage can reverse the iron toxicity and restore life expectancy
      to normal. Because of its familial occurrence all first-degree relatives of
      patients with hereditary hemochromatosis should be tested for the disease.

PMID- 12064862
TI  - Pathogenesis of hereditary hemochromatosis: genetics and beyond.
AB  - Hereditary hemochromatosis (HH) comprises several inherited disorders of iron
      homeostasis characterized by increased gastrointestinal iron absorption and
      secondary tissue iron deposition. The most common form of this disorder is called
      HFE-related HH and is caused by homozygosity for the C282Y mutation in the HFE
      gene. Recently, other less common hereditary forms of iron overload have been
      recognized and are designated as non-HFE-related HH. The identification and
      cloning of HFE and other genes involved in iron metabolism has greatly expanded
      our understanding of many aspects of HH. The introduction of a commercially
      available genetic test for the C282Y and H63D mutations of HFE allows
      presymptomatic diagnosis, and adds precision to studies of the population
      genetics of HFE-related HH. It is now recognized that a substantial proportion of
      C282Y homozygotes does not develop clinically significant iron overload, and
      modifier genes may be involved in this phenomenon. Mouse models of HH and cell
      culture studies have increased our understanding of the normal physiology and
      pathophysiology of iron homeostasis. Future investigations will refine our
      knowledge of the mechanisms of action of HFE protein, the phenotypic variability
      observed in persons homozygous for the C282Y mutation, and the mechanisms
      responsible for non-HFE-related HH.

PMID- 12064864
TI  - Population screening for hemochromatosis--are we finding people with a disease or
      a biochemical curiosity?
AB  - Hemochromatosis is a common genetic disease in which early diagnosis and
      treatment results in an excellent long-term prognosis. Population screening
      projects have been completed that included iron tests and genetic testing. In
      this review, the controversial issues surrounding population screening for
      hemochromatosis are explored in the context of available information from large
      screening studies.

PMID- 12064865
TI  - Iron in hepatitis C: villain or innocent bystander?
AB  - Elevations in serum transferrin-iron saturation and ferritin are common in
      patients with chronic hepatitis C infection, especially if they have concomitant
      elevations in serum aminotransferases. However, serum markers of iron stores do
      not accurately reflect hepatic iron content, or predict clinically important
      endpoints such as response to interferon and disease progression. In contrast,
      hepatic iron concentration, which is usually normal or only mildly elevated in
      chronic hepatitis C infection in the absence of cirrhosis, is one of the
      strongest predictors of response to interferon monotherapy. Iron depletion by
      phlebotomy consistently reduces serum aminotransferases and in combination with
      interferon may have improved antiviral efficacy compared to interferon alone.
      Unfortunately, no data are available on the role, if any, of iron depletion
      therapy, as an adjunct to interferon and ribavirin combination treatment. Future
      studies should focus on the efficacy of combining iron depletion with pegylated
      interferon and ribavirin and on the effect of long-term iron depletion on
      histologic progression of chronic hepatitis C infection.

PMID- 12064866
TI  - Sequence analysis of measles virus strains collected during the pre- and early
      vaccination era in Denmark reveals a considerable diversity of ancient strains.
AB  - A total of 199 serum samples from patients with measles collected in Denmark,
      Greenland and the Faroe Islands from 1964 to 1983 were analysed by PCR. Measles
      virus (MV) RNA could be detected in 38 (19%) of the samples and a total of 18
      strains were subjected to partial sequence analysis of the hemagglutinin gene.
      The strains exhibited a considerable genomic diversity, which is at odds with the
      assumption that one genome type prevailed among globally circulating MV strains
      prior to the advent of live-attenuated vaccines. Our data indicate that the
      similarity of the various vaccine strains is attributed to their having
      originated from the same primary isolate. Consequently, it is implied that a
      small number of clinical manifestations of MV worldwide from which strains
      similar to the vaccine strain were identified were vaccine related rather than
      being caused by members of a persistently circulating ancient genome type. The
      Danish pre- and early-vaccination era MV strains seem to change the evolutionary
      spectrum of genome types A, C2 and E into one coherent group, suggesting that the
      genome types of MV strains circulating in the world at present do not represent
      far ranging evolutionary lineages but merely members of an evolutionary continuum
      of pre-vaccination era MV strains which by chance or due to an improved
      capability survived the worldwide partial herd immunity accomplished through
      vaccination.

PMID- 12064867
TI  - Detection of orientation-specific anti-gp120 antibodies by a new N-glycanase
      protection assay.
AB  - Several functions have been assigned to the extensive glycosylation of HIV-1
      envelope glycoprotein gp120, especially immune escape mechanisms, but the
      intramolecular interactions between gp120 and its carbohydrate complement are not
      well understood. To analyse this phenomenon we established a new microwell
      deglycosylation assay for determining N-linked glycan accessibility after binding
      of gp120-specific agents. Orientation-specific exposition of gp120 in ELISA
      microplates was achieved by catching with either anti-C5 antibody D7324 or anti
      V3 antibody NEA-9205. We found that soluble CD4 inhibited the deglycosylation of
      gp120 only when gp120 was caught by D7324 and not by NEA9205. In contrast,
      antibodies from HIV-infected individuals inhibited the deglycosylation best when
      gp120 was caught by NEA9205. These results demonstrated that both the CD4-binding
      site and the epitopes recognised by antibodies from HIV-infected individuals have
      N-glycans in the close vicinity. However, the difference in gp120 orientation
      indicates that antibodies in HIV-infected individuals, at least partly, bind to
      epitopes different from the CD4-binding site. Finally, we determined the
      structural class of the glycan of one V1 glycosylation site of prototype HIV-1
      LAI gp120, which remained unsolved from previous studies, and found that it
      belonged to the complex type of glycans.

PMID- 12064868
TI  - Neuroendocrine differentiation in gastric adenocarcinomas associated with severe
      hypergastrinemia and/or pernicious anemia.
AB  - Patients with hypergastrinemia secondary to achlorhydria have an increased risk
      of developing ECL cell carcinoids and gastric adenocarcinomas. Hypergastrinemia
      is central in the pathogenesis of ECL cell carcinoids, but the link between
      gastrin and gastric carcinomas is controversial. During neoplastic transformation
      ECL cells may, however, lose many of their neuroendocrine characteristics, making
      them difficult to recognise as neuroendocrine with conventional
      immunohistochemical techniques. Neuroendocrine differentiation was therefore
      examined in eight gastric adenocarcinomas found in seven patients with severe
      hypergastrinemia and/or pernicious anemia using a monoclonal antibody towards
      chromogranin A and immunohistochemistry without and with a sensitive signal
      amplification technique. The Sevier-Munger method was used as a more specific
      marker of ECL cells. Seven of the carcinomas contained scattered neuroendocrine
      tumour cells. When using signal amplification, an increase in the number of
      immunoreactive neoplastic cells was seen. In many tumours, clusters or confluent
      sheets of such cells were disclosed, suggesting a neuroendocrine and ECL cell
      origin. These tumours may therefore be ECL cell carcinomas and hypergastrinemia
      may thus be involved in the tumourigenesis.

PMID- 12064869
TI  - Endemic nosocomial infections and misuse of antibiotics in a maternity hospital
      in Saudi Arabia.
AB  - Patients admitted during a 6-month period to a maternity hospital in Saudi Arabia
      were studied for nosocomial infections and misuse of antibiotics. Patient history
      and diagnosis on admission and subsequent clinical and laboratory data were
      analysed. Infection developing from 72 h after admission was considered
      nosocomial. Therapeutic and prophylactic data as recorded on the patients' charts
      were assessed for possible misuse of antibiotics. Of 3439 patients, 136 (4.0%)
      developed nosocomial infection: 2.0%, 8.9% and 37.7% in obstetric, gynaecologic
      and nursery patients, respectively. Infections among adults were mostly found in
      the urinary (44.4%) and lower genital (33.3%) tracts. Among newborns, over 70% of
      cases were eye and ear (29.8%), skin (26.2%) and blood (19.0%) infections. Gram
      negative bacteria caused 65.7% of the infections. Over 90% of the bacterial
      isolates were multidrug-resistant. About 24% of patients received single or
      multiple antibiotics; 57.2% were misused. The minimal hospital cost estimate for
      both nosocomial infections and misused antibiotics was US $318,705. The findings
      of this study, the first of its type in this region, should prompt improved
      infection control measures as well as educational and antibiotic restriction
      interventions.

PMID- 12064870
TI  - Generation of EBV-specific CTLs suitable for adoptive immunotherapy of EBV
      associated lymphoproliferative disease following allogeneic transplantation.
AB  - Lymphoproliferative disease induced by EBV (EBV-LPD) is a complication of
      allogeneic transplantation caused by T-cell immunodeficiency. EBV-LPD responds
      poorly to conventional treatment modalities. Recently, adoptive transfer of EBV
      specific, HLA-class I-restricted CTL lines was shown to be effective both as
      prophylaxis and as treatment of EBV-LPD. The CTL lines are produced by in vitro
      selection of EBV-specific memory T cells contained in MNC of EBV-seropositive
      individuals by repeated stimulation with irradiated EBV-transformed cells. The
      non-EBV-reactive and potentially alloreactive cells remain unactivated. Twenty
      one CTL lines were initiated. All were successfully generated and shown to be HLA
      restricted and EBV-specific as well as CD8/CD4 and CD45RO positive T cells. The
      majority of the CTL lines were generated from BMT donors, but two CTL lines were
      obtained from solid organ transplant recipients receiving immunosuppression.
      Evidence of probable in vivo efficacy is presented. Development of efficient
      adoptive T-cell strategies for EBV-positive malignancies could serve as a model
      for treatment of other viral or malignant disorders.

PMID- 12064871
TI  - Platelet-activating factor and lyso-PAF possess direct antimicrobial properties
      in vitro.
AB  - The effects of platelet-activating factor (PAF) and lyso-platelet-activating
      factor (L-PAF) at concentrations of 0.25-20 microg/ml on potassium transport and
      growth of gram-positive and gram-negative bacteria have been investigated in
      vitro and compared with those of lysophosphatidylcholine (LPC). Potassium
      transport was determined using 86Rb+ as tracer, while growth was measured
      according to the extent of uptake of radiolabeled amino acids. All of the test
      phospholipids caused dose-related inhibition of 86Rb+-uptake and growth of gram
      positive bacteria, the order of potency being PAF>LPC>L-PAF. Gram-negative
      bacteria, on the other hand, were less sensitive to the inhibitory effects of the
      phospholipids on K+ transport and growth. Some, but not all, of the gram-positive
      and gram-negative bacteria were able to degrade LPC, but not PAF or L-PAF,
      demonstrating that enzymatic degradation of phospholipids does not explain the
      differential sensitivity to these agents. The bioactive phospholipids LPC, PAF
      and L-PAF may represent an oxygen-independent antimicrobial host defense system
      operative primarily against gram-positive bacteria.

PMID- 12064872
TI  - p53 gene mutation and MDM2 overexpression in a case of primary malignant fibrous
      histiocytoma of the jejunum.
AB  - Primary malignant fibrous histiocytoma of the gastrointestinal tract is extremely
      rare. To date, only 10 cases of primary malignant fibrous histiocytoma arising in
      the small intestine have been reported in the English literature. We describe
      here the genetic alterations and morphologic features of a primary malignant
      fibrous histiocytoma arising in the jejunum. Immunohistochemically, the tumor
      cells expressed vimentin, CD68 and alpha-1-antitrypsin, but were negative for
      other markers. Ultrastructurally, they showed features of fibroblasts and
      histiocytes. Immunohistochemical overexpression of p53 and MDM2 was observed.
      Mutation analysis of the p53 gene detected a missense mutation in codon 158 of
      exon 5. Our results suggest that p53 gene mutations and MDM2 overexpression may
      play an important role in the tumorigenesis. To our knowledge, the present report
      is the first genetic study of this rare lesion.

PMID- 12064873
TI  - Histologic changes in thyroid nodules after percutaneous ethanol injection in
      patients subsequently operated on due to new focal thyroid lesions.
AB  - This paper reports macro- and microscopic changes in hyperfunctioning thyroid
      nodules (HTN), initially diagnosed as solitary, in patients treated with
      percutaneous ethanol injection (PEI). In 78 patients, benign solitary HTN were
      diagnosed by clinical and hormonal examination. High resolution ultrasonography
      confirmed the solitary nodule. The results of fine needle aspiration biopsy
      (FNAB), performed twice, ruled out malignancy of the nodule. The patients were
      referred for PEI treatment. At 1-year follow-up, newly formed thyroid nodules,
      whose volumes increased, were detected in five patients (6.4%) with HTN,
      initially diagnosed as solitary. Therefore, these patients were operated on.
      Subtotal thyroidectomy was performed. At the intraoperative macroscopic
      evaluation, a hard fibrous solid mass was found in place of three nodules (n1,
      n2, n3) following PEI treatment. The middle area of the cut surface of PEI
      treated nodules (n4 and n5) in the other two patients was firm and haemorrhagic,
      surrounded by a fibrous mass. Histolopathologic examination of n1, n2 and n3
      revealed fibrosis and hyalinosis. Examination of n4 and n5 showed haemorrhagic
      necrosis in the middle of the nodules surrounded by fibrous tissue.

PMID- 12064874
TI  - Comparison of methods of microvascular staining and quantification in prostate
      carcinoma: relevance to prognosis.
AB  - High microvascular density in prostate carcinomas may indicate poor prognosis.
      Our aim was to compare two different anti-endothelial antibodies and two
      different ways of evaluating microvascular scores in hot spots (microvessel
      density (MVD) and Chalkley counts). Adjacent serial sections of formalin-fixed,
      paraffin-embedded tumor specimens from TURPs on 51 consecutive patients with
      prostate carcinoma were immunostained for CD34 and von Willebrand Factor (vWF).
      Estimates of microvascular density were based on projecting a 10 x 10 grid or a
      Chalkley grid onto a vascular hot spot of the invasive prostate carcinoma. Anti
      CD34 antibodies stained microvessels in all 51 tumors, whereas anti-vWF
      antibodies in 6 tumors resulted in intense background staining causing omission
      of these. Anti-CD34 antibodies highlighted significantly more microvessels than
      anti-vWF antibodies, and the anti-CD34 vascular scores with either of the
      counting methods were significantly correlated, which was not the case with vWF.
      Both grids used on anti-CD34-stained sections resulted in vascular scores that
      could separate the tumors into prognostic groups. This was not possible using the
      Chalkley grid on vWF-stained tumors. In conclusion, anti-CD34 antibodies are
      sensitive endothelial markers in prostate carcinoma, and the investigated
      counting methods are compatible. Moreover, high vascular scores seem to carry a
      poor prognosis.

PMID- 12064875
TI  - Histological examinations of bone and cartilage in the axial skeleton of human
      triploidy fetuses.
AB  - The aim of this study was to examine histologically bone and cartilage in
      vertebral corpora of axial skeletons of eight human triploid fetuses, gestational
      ages 14-25 weeks, CRL 100-200 mm. The results were compared to earlier studies on
      vertebral development in trisomies 21, 18, 13, and to normal corpora development.
      After radiography in frontal and lateral projections, the vertebral column was
      sectioned into cervical, thoracic and lumbar segments, decalcified, dehydrated,
      and embedded in paraffin. The blocks were serially sectioned in the vertical
      plane and stained with Toluidine blue and Alcian blue/van Gieson. The
      radiographic characteristics of the vertebral corpora observed in frontal and
      lateral projection varied from small cleft vertebral corpora to fusions between
      the individual corpora. Histological examination of the vertebral corpora
      confirmed the abnormal pattern of ossification seen radiographically. As a new
      finding abnormal metachromasia of the ground substance was observed in the
      cartilage. Marked borderlines were registered in the cartilage between regions
      with differences in metachromasia. These borderlines were similar but more
      extensive than borderlines observed previously in trisomies 21, 18 and 13.

PMID- 12064876
TI  - The molecular biology of distraction osteogenesis.
AB  - Distraction osteogenesis has become a mainstay in bone tissue engineering and has
      significantly improved our armamentarium for reconstructive craniomaxillofacial
      procedures. However, although the biomechanical, histological, and
      ultrastructural changes associated with distraction osteogenesis have been widely
      described, the molecular mechanisms governing the formation of new bone in the
      interfragmental gap of gradually distracted bone segments remain largely unclear.
      Recently, a rat model of mandibular distraction was described that provides an
      excellent environment for deciphering the molecular mechanisms that mediate
      distraction osteogenesis. This article presents the hypotheses and current
      research that have furthered knowledge of the molecular mechanisms that govern
      distraction osteogenesis. Recent studies have implicated a growing number of
      cytokines that are intimately involved in the regulation of bone synthesis and
      turnover. The gene regulation of numerous cytokines (transforming growth factor
      beta1, -beta2, -beta3, bone morphogenetic proteins, insulin-like growth factor-1,
      fibroblast growth factor-2) and extracellular matrix proteins (osteonectin,
      osteopontin) during distraction osteogenesis have been best characterized and are
      discussed in this article. It is believed that understanding the biomolecular
      mechanisms that mediate membranous distraction osteogenesis may guide the
      development of targeted strategies designed to improve distraction osteogenesis
      and accelerate bone healing.

PMID- 12064877
TI  - The proximal tibia donor site in cleft alveolar bone grafting: experience of 75
      consecutive cases.
AB  - BACKGROUND: The optimum donor site for cleft alveolar bone grafting is still
      debated. Donor site morbidity is an important factor in deciding the site for
      harvest of cancellous bone. Use of the proximal tibia as donor site is associated
      with few complications. The occurrence of a proximal tibia fracture following
      cancellous bone harvest from this site, prompted a review of the last 75
      consecutive cases carried out at our unit. MATERIAL AND METHOD: The medical notes
      of 75 consecutive patients undergoing cleft alveolar bone graft were reviewed and
      postal questionnaires were sent to patient's parents and family physicians. The
      review focused on donor site morbidity. RESULTS: Fracture of the proximal tibia,
      a hitherto unreported complication, occurred in two out of 75 cases (2.7%) within
      our series. Post-operative mobilization was achieved rapidly with normal joint
      function and donor site healing progressed satisfactorily in all cases. In 1 out
      of 75 cases the graft was repeated at a later date due to recipient site
      infection. The incidence of other morbidity was low with most representing local
      complications only. Length of hospital stay was 3 days (range 2-5 days).
      CONCLUSION: Based on our findings we feel that the proximal tibia offers a
      reliable site for harvest of sufficient quantities of good quality cancellous
      bone. Recommendations are made as to the technique of bone harvest, to minimize
      the fracture risk.

PMID- 12064879
TI  - Introduction of a three-dimensional anthropometry of the viscerocranium. Part I:
      measurement of craniofacial development and establishment of standard values and
      growth functions.
AB  - BACKGROUND AND OBJECTIVE: The analysis of lateral cephalograms is based on many
      vague landmarks that vary intra- and inter-individually. Exposure to radiation
      and high-quality equipment are essential, while identical object positioning is
      almost impossible. Anthropometry as presented in the literature is time consuming
      and cannot reproduce cranial three-dimensionality. Poor landmark definitions and
      resilience of the soft tissue foster systematic measurement errors. We used few
      easily detectable and accessible landmarks that are closely related to underlying
      bone. The distances measured were visualized three-dimensionally. MATERIAL AND
      METHODS: Measurements from 540 volunteers were reconstructed. Reliability was
      assessed through repeated measurements. Corresponding distances were measured in
      lateral cephalograms taken the same day. RESULTS: The age- and sex-related mean
      values and 95%-percentiles were visualized as growth functions. The intra
      individual relative error in anthropometry was 3.7%, in roentgenocephalometry
      0.9%. The inter-individual error was 5.8% for anthropometry and 3.6% for
      roentgenocephalometry. CONCLUSION: Applied anthropometry as described in the
      paper is reliable and valid for measuring craniofacial growth, arriving at a
      diagnosis and 'monitoring' treatment results. The relative measurement error in
      anthropometry appear to be smaller than the systematic magnification and
      distortion found in lateral cephalograms.

PMID- 12064880
TI  - Introduction of a three-dimensional anthropometry of the viscerocranium. Part II:
      evaluating osseous and soft tissue changes following orthognathic surgery.
AB  - BACKGROUND AND OBJECTIVE: Anthropometric measurements, described and assessed in
      Part I of this article were applied in dysgnathic patients. Diagnosis, surgical
      planning and follow-up were performed and soft tissue ratios quantified. MATERIAL
      AND METHODS: One hundred and seventy-five anthropometric measurements and 146
      cephalograms of 100 patients were included. Forty-five patients were analysed
      before and after surgery. Ten randomly selected patients were re-measured
      directly by two investigators for reliability and validity assessment. RESULTS:
      Manoeuvres that expanded the facial skeleton such as maxillary or mandibular
      advancements or maxillary elongations generally had a greater soft tissue impact
      than setbacks or maxillary impactions. A 1.4% intra-observer and a 2.6% inter
      observer error was apparent with anthropometry. Concordance of anthropometry with
      roentgenocephalometry (p<0.04) was found by paired t -test. CONCLUSION: The
      anthropometry allowed reliable and objective, independent calculation of cranial
      bone relations and soft tissue projection. It is also sensitive to facial
      asymmetry. Easy application, versatility and an economic price for the assessment
      of facial proportions, soft tissue ratios, operation planning and follow-up were
      obvious.

PMID- 12064881
TI  - Positional stability following intentional posterior ostectomy of the distal
      segment in bilateral sagittal split ramus osteotomy for correction of mandibular
      prognathism.
AB  - PURPOSE: In order to minimize post-operative relapse after mandibular setback
      using bilateral sagittal split ramus osteotomy, we have recently tried a
      technique, i.e. intentional ostectomy of the posterior part of the distal
      segment. The aim of this study was to evaluate the effects of this technique on
      the frequencies and extent of post-operative relapse. PATIENTS: This study was
      based on 61 cases of mandibular prognathism. The traditional sagittal split was
      performed in 24 cases (average age: 22.0+/-3.8) as a control group and the
      technique of additional distal ostectomy was used in the other 37 cases (average
      age: 23.2+/-3.2) as a test group. METHODS: Horizontal and vertical changes in the
      position of the body of the mandible were measured to determine the amount of
      long-term post-operative relapse. The amount of relapse was compared between
      groups and the statistical significance of the differences was evaluated.
      RESULTS: The relapse index of the test group was significantly lower than that of
      the control group in the 6- and 12-month post-operative periods (p>0.005). The
      horizontal relapse index and facial length relapse index of the test group were
      lower than those of the control group 12 months post-operatively (p<0.05).
      CONCLUSION: This method should be considered as a useful method to maximise long
      term post-operative stability.

PMID- 12064882
TI  - Blood supply of the mandibular cortex: an experimental study in Gottingen
      minipigs with special reference to the condyle.
AB  - INTRODUCTION: Blood supply of the mandible is an important factor that influences
      bone growth and bone repair. MATERIAL AND METHODS: An experimental study was
      carried out in 24 mandibles of 12 Gottingen minipigs to study the blood supply of
      the mandibular cortex. RESULTS: Endosteal blood supply prevails in the cranial
      part of the mandible including the condyle, whilst periosteal blood supply
      predominates in the caudal part of the mandible, the body. The two forms of blood
      supply are in balance in the ascending ramus and the angle of the mandible.
      CONCLUSION: The mandibular cortex can be divided into three parts, each having
      different sources of blood supply. The results of this study may be of
      significance for man and could help to understand some pathological disorders of
      the mandible.

PMID- 12064883
TI  - Simultaneous bimaxillary alveolar ridge augmentation by a single free fibular
      transfer: a case report.
AB  - Class VI atrophy according to Cawood still represents a major challenge in pre
      prosthetic surgery. Reconstruction of mandibular and maxillary bony defects using
      microvascular techniques is safe and reliable. The fibula, due to its
      morphological properties, is ideal for alveolar ridge augmentation and its donor
      site morbidity is the lowest among vascularized bone flaps. In this paper, we
      report the first case, to our knowledge, of extreme atrophy of both jaws,
      successfully treated by simultaneous bony augmentation of the maxillary and
      mandibular alveolar ridges with just one free fibula flap. Pre-operative
      planning, surgical technique and prosthetic restoration are discussed in detail.

PMID- 12064885
TI  - Outcome of surgery for adenoid cystic carcinoma of head and neck region.
AB  - INTRODUCTION: Adenoid cystic carcinoma is an uncommon malignant epithelial tumour
      of salivary glands. The treatment of choice for these tumours is considered by
      some to be radical surgery, combined in many centres with postoperative
      radiotherapy. The goal of such treatment is local control and preservation of
      function. AIMS: The aim of the retrospective study was to analyse the results of
      surgery for patients with adenoid cystic carcinoma treated at the Institute of
      Oncology in Gliwice during the period of 1970-1989. MATERIAL: The analysed group
      includes 47 patients with adenoid cystic carcinoma. All patients underwent macro-
      and microscopically proven radical resection of the primary lesion located in
      major or minor salivary glands. RESULTS: Five- and 10-year survival rate was 85%
      and 47%, respectively, and 5-year disease-free survival rate was 79%. As the
      group of patients treated with surgery and radiotherapy was too small (nine
      cases), the results of combined treatment were not analysed. Local recurrence
      after surgery occurred in 21% of patients in different time intervals (even as
      long as 10 years after completion of treatment). CONCLUSION: High risk of local
      recurrence after surgery suggests that postoperative radiotherapy should always
      be given. Late development of local recurrences suggests that follow-up should be
      for a minimum of 10 years.

PMID- 12064884
TI  - In vitro cytotoxic dose-relation of cisplatin and sodium thiosulphate in human
      tongue and oesophageal squamous carcinoma cell lines.
AB  - BACKGROUND: Intraarterial chemotherapy of oral and oropharyngeal cancer with
      cisplatin (cis-diamminedichloroplatinum [II]) has experienced a revival in the
      last decade. Side-effects of the therapy were very low with concomitant systemic
      infusion of the neutralizing agent sodium thiosulphate. The requisite dose of the
      chemotherapeutic agent which safely leads to apoptosis of oral cancer cells has
      not yet been assessed in vitro, nor has the combination of cisplatin and sodium
      thiosulphate been examined for the potential reduction of cytotoxicity in oral
      cancer cells. STUDY DESIGN: In a panel of two tongue squamous cancer cell lines
      and an oesophageal cancer cell line as control and comparison, cisplatin (0.2-10
      microgram/ml) was combined with sodium thiosulphate (0-0.5 mg/ml). RESULTS: 10
      microgram/ml of cisplatin proved to be 100% antiproliferative, while any
      additional concentration of sodium thiosulphate decreased this effect. At the
      maximum dose of cisplatin, a sodium thiosulphate/cisplatin concentration relation
      of less than 6:1 still effected cytotoxic activity of >80%. An increase of
      cisplatin concentration led to higher cytotoxicity irrespective of sodium
      thiosulphate concentration. The oesophageal cell line was more sensitive to
      cisplatin and to sodium thiosulphate than the tongue cell lines. CONCLUSIONS: In
      this study, it was found that high concentrations of cisplatin are necessary in
      oral cancer to reach cytotoxic levels which support high-dose intraarterial
      chemotherapy by which these levels might be reached. A sodium
      thiosulphate/cisplatin concentration ratio within the tumour of less than 6:1 may
      be allowed without compromising the cytotoxic activity of cisplatin.

PMID- 12064886
TI  - Pneumosinus dilatans of the frontal and ethmoidal sinuses: case report.
AB  - Enlargement of paranasal sinuses with air is rare with less than 50 cases
      reported in the medical literature. This craniofacial malformation was first
      described by Meyes in 1898 and its aetiology still remains unknown. Local pain,
      ocular alterations, anosmia, headache and cosmetic disturbances are the most
      common symptoms. We present a case of pneumosinus dilatans diagnosed in a male, 8
      years of age. He presented with left fronto-orbital bossing that enlarged slowly
      until he was 12 years old, at which point its growth appeared to increase
      dramatically. Computerized tomography revealed an enlargement of the frontal and
      ethmoidal sinuses, with marked deformation of the anterior wall and of the roof
      of the left frontal sinus, as well as the roof of the ethmoid and upper sinus
      medial orbital wall. The sinus walls were of normal thickness. Access was via a
      bicoronal incision and osteotomy of the deformed fronto-orbital bossing.
      Reconstruction was undertaken with a periosteal flap and hydroxyapatite bone
      cement (Norian) following sinus mucosal stripping and obliteration of the sinus
      with fat. Six months postoperatively, the patient was without recurrence and had
      a good cosmetic result.

PMID- 12064887
TI  - A complication of submandibular intubation in a panfacial fracture patient.

PMID- 12064888
TI  - Perinatal growth failure: the road to obesity, insulin resistance and
      cardiovascular disease in adults.
AB  - A continuum of increasing risk of adulthood diseases, such as cardiovascular
      disease, type 2 diabetes and hypertension, with decreasing size at birth is now
      well-reported and a number of different hypotheses have been proposed.
      Birthweight links with disease risk markers such as insulin resistance are
      apparent from childhood, particularly when low birthweight is followed by rapid
      postnatal weight gain and childhood obesity. Such growth patterns follow fetal
      growth restraint, associated with maternal-uterine factors such as primiparity,
      smoking, maternal genes or variations in maternal diet. The fetal metabolic and
      hormonal responses to intrauterine growth restraint and to rapid postnatal growth
      are likely to be key to the early pathogenesis of adulthood disease. Thrifty
      fetal genotypes may enhance these adaptations and improve perinatal survival but
      predispose to adulthood disease. Their historical selection could explain high
      prevalences of type 2 diabetes in some ethnic groups, and their identification
      could allow targeting of potential interventions.

PMID- 12064889
TI  - Childhood-onset growth hormone (GH) deficiency in adult life.
AB  - Over the last decade GH replacement therapy for adults has progressed in status
      from research study to a mainstream clinical indication. An area ripe for further
      research, however, is the difference between adults who developed GHD before and
      after completion of growth and puberty. That differences exist, not only in
      aetiology, but also in phenotype and response to GH therapy is clear. However,
      whether these differences are intrinsic to the timing of onset of GHD, or related
      to secondary factors including the method of assessment or dose of GH employed is
      uncertain. This chapter discusses the current state of knowledge in this area and
      poses further questions, not only for the researcher attempting to understand the
      mechanisms underlying these differences, but also for the physician seeking to
      ameliorate the impact of GHD in patients who acquired GHD in childhood.

PMID- 12064890
TI  - Childhood growth and adult cancer.
AB  - Associations between different patterns of childhood growth and later adult
      health have recently received much attention. Most studies have found higher
      mortality in shorter people, explained by their higher incidence of
      cardiorespiratory disease. In this chapter, associations of cancer with markers
      of growth at different developmental phases - infancy, childhood and puberty -
      and with final adult height are reviewed. The relationship between birthweight
      and cancer is generally positive, with the greatest risk among high-birthweight
      babies. Childhood and adult tallness are related to higher cancer risk. This is
      particularly evident for cancers of the breast, prostate, colo-rectum,
      haematopoietic system and endometrium. Leg length may be more strongly associated
      than trunk length with cancer risk. Possible explanations for these findings are
      discussed in relation to nutritional intake and hormonal levels.

PMID- 12064891
TI  - The impact and management of Turner's syndrome in adult life.
AB  - Turner's syndrome (TS), caused by an absent or structurally abnormal X
      chromosome, affects 1 in 2500 live female births. Most medical attention has
      focused on the attainment of final height in childhood and, when this has been
      achieved, many women are discharged to primary care. It has become increasingly
      evident that adults with Turner's syndrome are susceptible to a range of
      disorders such as osteoporosis, hypothyroidism and diabetes. Because of these,
      and because of the need for long-term oestrogen replacement, it seems most
      practical for adult health surveillance in TS to come under the remit of the
      endocrinologist. It must be accepted, however, that the reduced life expectancy
      in women with TS is largely accounted for by cardiovascular disease. Also, the
      commonly observed social isolation in adults with TS can be linked to deafness
      that is increasingly prevalent in an ageing group. Co-ordination of all these
      issues requires a dedicated multidisciplinary clinic along the lines of those in
      place in diabetes.

PMID- 12064892
TI  - Adult polycystic ovary syndrome begins in childhood.
AB  - Polycystic ovary syndrome (PCOS) frequently presents during adolescence and is
      the commonest cause of menstrual irregularity and hirsutism. The characteristic
      endocrine abnormalities include hypersecretion of androgens and LH. Metabolic
      dysfunction is also a feature of many young women with PCOS. Hyperinsulinaemia
      and insulin resistance, which can be regarded as an exaggeration of the normal
      metabolic changes that occur during puberty, are further amplified by obesity.
      The aetiology of PCOS is uncertain but there is evidence for a primary
      abnormality of ovarian androgen production which is manifest at puberty but may
      have its origins in childhood or even during fetal development.

PMID- 12064893
TI  - Long-term consequences of childhood-onset congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) is a general term applied to several
      diseases caused by inherited defects of cortisol synthesis. The most common of
      these is steroid 21-mono-oxygenase (also termed 21-hydroxylase) deficiency (CAH
      21OHD), found in approximately 1:10 000-1:15 000 live births. Potentially lethal
      adrenal insufficiency is characteristic of about two-thirds to three-quarters of
      patients with the classic salt-wasting form of CAH-21OHD. Non-salt-wasting forms
      of CAH-21OHD may be diagnosed based in part on genital ambiguity in affected
      newborn females, and/or by later evidence of androgen excess in members of either
      sex. Non-classical CAH-21OHD may be detected in up to 1-3% of certain
      populations, and is often mistaken for idiopathic precocious pubarche in children
      or polycystic ovary syndrome in young women. This chapter addresses issues
      relating to long-term consequences in adult life of CAH-21OHD diagnosed in early
      childhood or adolescence.

PMID- 12064894
TI  - Impact of exposure to endocrine disrupters in utero and in childhood on adult
      reproduction.
AB  - Recent reports have demonstrated a decline in human male reproductive health:
      high and probably increasing prevalence of cryptorchidism and hypospadias, low
      and probably decreasing semen quality, a rising incidence of testicular cancer
      and a growing demand for assisted reproduction. These changes seem to be
      interrelated and may be symptoms of a common underlying entity, the testicular
      dysgenesis syndrome, with foundations in fetal life due to adverse environmental
      influences. Wildlife experience and animal studies have provided evidence that
      fetal or perinatal exposure to endocrine disrupters results in disturbed sexual
      differentiation and urogenital malformations followed by decreased reproductive
      health in adult life. This chapter reviews existing evidence for a connection
      between (i) exposure to endocrine disrupters in fetal life and childhood and (ii)
      adult reproductive health in humans. This topic is not only relevant to basic
      scientists but also to clinical endocrinologists, who should also be encouraged
      to participate in research concerning this problem.

PMID- 12064895
TI  - Late reproductive sequelae following treatment of childhood cancer and options
      for fertility preservation.
AB  - The successful treatment of childhood cancer can be associated with impaired
      gonadal function in adulthood. Chemotherapy and radiotherapy may damage germ-cell
      spermatogonia, resulting in impaired spermatogenesis or sterility in the male, or
      may hasten oocyte depletion with truncated fecundity and premature menopause in
      the female. The only established option in current clinical practice for
      preserving male fertility is cryopreservation of spermatozoa. The only strategy
      currently available for preserving female fertility is cryopreservation of
      embryos. Harvesting and storage of ovarian cortical tissue from girls and young
      women before potentially gonadotoxic chemotherapy has been available in a number
      of centres but there have been no live births and the procedure remains
      experimental. Standards for best practice in the cryopreservation of gonadal
      tissue, including the criteria for providing a service, patient identification
      and selection, standard operating procedures and requirements for safe storage,
      remain to be defined. Recent advances in assisted reproduction may circumvent
      natural conception barriers and the implications of impaired DNA integrity may be
      manifest as an increased risk of congenital abnormalities and chromosomal
      disorders in the offspring. In this chapter we consider the late reproductive
      sequelae following treatment for childhood cancer and options for fertility
      preservation.

PMID- 12064896
TI  - Late endocrine, metabolic and skeletal sequelae following treatment of childhood
      cancer.
AB  - With an ever increasing adult population of childhood cancer survivors there is a
      need to focus on the late effects of cancer therapy. It is essential that, after
      discharge from the paediatric oncologists, the patients are not lost from the
      health system but are under continued surveillance with access to the appropriate
      physicians. Endocrine and metabolic consequences may affect a patient's life both
      soon after cancer treatment and also for many years in the future. In this review
      we consider the following potential problems: growth hormone deficiency and
      replacement in adulthood, cardiovascular risk factors, osteopaenia, thyroid and
      parathyroid dysfunction.

PMID- 12064897
TI  - Prenatal and childhood influences on osteoporosis.
AB  - Osteoporosis is a major cause of morbidity and mortality through its association
      with age-related fractures. Although most effort in fracture prevention has been
      directed at retarding the rate of age-related bone loss, and reducing the
      frequency and severity of trauma among elderly people, evidence is growing that
      peak bone mass is an important contributor to bone strength during later life.
      The normal patterns of skeletal growth have been well characterized in cross
      sectional and longitudinal studies. It has been confirmed that boys have higher
      bone mineral content, but not volumetric bone density, than girls. Furthermore,
      in both genders there is a dissociation between the peak velocities for height
      gain and bone mineral accrual. Puberty is the period during which volumetric
      density appears to increase in both axial and appendicular sites. Many factors
      influence the accumulation of bone mineral during childhood and adolescence,
      including heredity, gender, diet, physical activity, endocrine status and
      sporadic risk factors such as cigarette smoking. Measures for maximizing bone
      mineral acquisition, particularly through encouraging physical activity and
      adequate dietary calcium intake, are likely to affect the risk of fracture in
      later generations. In addition to these modifiable factors during childhood,
      evidence has also accrued that the risk of fracture might be programmed during
      intrauterine life. Epidemiological studies have demonstrated a relationship
      between birthweight, weight in infancy and adult bone mass. This appears to be
      mediated through modulation of the set-point for basal activity of pituitary
      dependent endocrine systems such as the hypothalamic - pitutiary - adrenal (HPA)
      and growth hormone/insulin-like growth factor I (GH/IGF-I) axes. Maternal
      smoking, diet and physical activity levels appear to modulate bone mineral
      acquisition during intrauterine life; furthermore, both low birth size and poor
      childhood growth are directly linked to the later risk of hip fracture. The
      optimization of maternal nutrition and intrauterine growth should also be
      included within preventive strategies against osteoporotic fracture, albeit for
      future generations.

PMID- 12064898
TI  - Long-term consequences of congenital hypothyroidism in the era of screening
      programmes.
AB  - Newborn screening for congenital hypothyroidism (CH), is one of the major
      achievements of medicine because early diagnosis and treatment has resulted in
      normal development in the vast majority of cases. However, all studies on outcome
      report up to 10% of patients with residual problems regarding mental development
      and neurological symptoms despite early diagnosis. Factors clearly associated
      with a less favourable outcome are late onset and an inadequate dosage of thyroid
      hormone substitution, a poor social-economic environment and compliance problems,
      while the impact of severity of CH at diagnosis on outcome is not completely
      settled, although most studies demonstrate a correlation between severity of
      hypothyroidism and poorer outcome. More recently in a few cases the molecular
      basis of CH has been clarified. It has become evident that, in some patients with
      persistent mental retardation and neurological symptoms, defects in transcription
      factors which are expressed in the thyroid gland as well as in the central
      nervous system (CNS) during embryonic development cause both defective thyroid
      and CNS development. The clarification of further molecular defects which affect
      the thyroid gland and brain development will help us to understand the poor
      outcome of patients with CH in the era of newborn screening and these diagnostic
      advances will ensure adequate counselling and care for these patients.

PMID- 12064901
TI  - Hematologically important mutations: glucose-6-phosphate dehydrogenase.

PMID- 12064902
TI  - Severe jaundice in a patient with a previously undescribed glucose-6-phosphate
      dehydrogenase (G6PD) mutation and Gilbert syndrome.
AB  - A patient with chronic hemolytic anemia and G6PD deficiency was noted to be
      severely jaundiced and to have a high serum ferritin level. Analysis of his DNA
      revealed only heterozygosity for the c.187 C-->G (H63D) mutation of HFE, but
      showed that he was homozygous for the UDP glucuronosyltransferase promoter
      mutation of Gilbert's disease and that he had a previously undescribed mutation
      of G6PD, c.832 T-->C (Ser278Pro). The new variant was named G6PD La Jolla.

PMID- 12064903
TI  - Control of analyzer slope and intercept in the measurement of packed red cell
      volume (PCV): part I.
AB  - Five multichannel hematology analyzers (four different models) were evaluated to
      determine the ability of analyzers to correctly measure packed cell volume (PCV)
      values across the clinically relevant range. A sixth analyzer (fifth model) was
      subsequently included using archival data. Twenty-two different blood samples
      with PCVs ranging from 0.2 to 0.6 L/L were run in duplicate on each analyzer.
      Duplicate reference PCV determinations were also done using the recently
      described ICSH-recommended reference method. Simultaneously, a simpler "surrogate
      reference" procedure was performed in duplicate. Analyzer values were compared to
      ICSH reference and to surrogate reference PCV values using Deming regression
      analysis. Compared to either reference, all analyzers showed a slope of less than
      1.0, thereby overestimating the PCV at 0.2 L/L and underestimating the PCV at 0.6
      L/L to some extent. This outcome was surprising. Deming regression slopes would
      be expected to average at 1.0. Instruments whose slopes are significantly less
      than 1.0 will show decreased sensitivity to both anemic and polycythemic
      patients. We know of no inherent reason why multichannel analyzers should behave
      in this fashion.

PMID- 12064904
TI  - Control of analyzer slope and intercept in the measurement of packed red cell
      volume (PCV): part II.
AB  - A majority of packed cell volume (PCV) assays performed in the United States are
      performed by multichannel hematology analyzers rather than by centrifugation of
      blood samples in glass capillary tubes. PCV results from both analytical
      approaches were compared to the recently described ICSH reference method to
      determine the effect of assay slope on clinical utility. Though not controllable
      by the end user, the slope of the PCV assay versus the reference was satisfactory
      when performed in centrifuged glass capillaries. In the small sample of
      multichannel analyzers surveyed, only two of six machines functioned as well in
      this respect as did the glass capillaries. The worst of the unsatisfactory
      multichannel analyzers would have identified correctly only about half of the
      anemic and the polycythemic patients in the 12,623 males surveyed in the Third
      National Health and Nutrition Examination Survey (NHANES III). The performance on
      the females in this U.S. Department of Health and Human Services study would have
      been similarly poor. It is important that manufacturers of multichannel analyzers
      attend to the slopes of their PCV assays if the results are to be diagnostically
      useful.

PMID- 12064905
TI  - Analysis of betaS and betaA genes in a Mexican population with African roots.
AB  - To investigate the origin of the beta(A) and beta(S) genes in a Mexican
      population with African roots and a high frequency of hemoglobin S, we analyzed
      467 individuals (288 unrelated) from different towns in the states of Guerrero
      and Oaxaca in the Costa Chica region. The frequency of the sickle-cell trait was
      12.8%, which may represent a public health problem. The frequencies of the beta
      haplotypes were determined from 350 nonrelated chromosomes (313 beta(A) and 37
      beta(S)). We observed 15 different beta(A) haplotypes, the most common of which
      were haplotypes 1 (48.9%), 2 (13.4%), and 3 (13.4%). The calculation of pairwise
      distributions and Nei's genetic distance analysis using 32 worldwide populations
      showed that the beta(A) genes are more closely related to those of Mexican
      Mestizos and North Africans. Bantu and Benin haplotypes and haplotype 9 were
      related to the beta(S) genes, with frequencies of 78.8, 18.2, and 3.0%,
      respectively. Comparison of these haplotypes with 17 other populations revealed a
      high similitude with the population of the Central African Republic. These data
      suggest distinct origins for the beta(A) and beta(S) genes in Mexican individuals
      from the Costa Chica region.

PMID- 12064907
TI  - Congenital transcobalamin II deficiency due to errors in RNA editing.
AB  - Transcobalamin II (TCII) is a plasma protein essential for the transport and
      cellular uptake of vitamin B12 (B12; cobalamin, Cbl). Congenital deficiency of
      functional TCII is an autosomal recessive genetic disorder that results in
      clinical B12 deficiency usually within several months following birth. In this
      report, we describe the molecular basis for TCII deficiency in two patients who
      developed a megaloblastic anemia in early infancy. The serum of both patients
      contained immunoreactive TCII that did not bind [57Co]Cbl. The fibroblasts from
      each patient secreted a similarly nonfunctional TCII, yet full-length TCII
      transcripts were identified by Northern blot. Overlapping cDNA fragments were
      generated by reverse transcription-polymerase chain reaction and several
      mutations were identified in the coding region of the cDNA, one of which was
      common to both patients. However, amplification of the corresponding regions of
      the gene from genomic DNA failed to identify these mutations. These findings were
      confirmed by replicate analyses and support the proposal that a variance in RNA
      editing is the likely mechanism for the mutations that resulted in the expression
      of a nonfunctional TCII protein in these patients.

PMID- 12064906
TI  - Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease.
AB  - The objective of this study was to evaluate the efficacy and safety of low-dose
      substrate balance therapy with OGT 918 for the treatment of adults with Gaucher
      disease. Eighteen patients with Gaucher disease from two centers were enrolled in
      an open-label 6-month study of OGT 918, 50 mg taken three times daily (TID),
      followed by an optional extended-use phase. Changes in liver and spleen volume at
      6 and 12 months, as well as routine hematological and biochemical parameters on a
      monthly basis, were evaluated. During the extension, dosage was increased to 100
      mg TID in patients in one center to improve the response. Seventeen patients
      completed 6 months; of 16 patients in the extension phase, 13 were evaluable at
      12 months. Percentage changes in liver (-5.9%, P = 0.007) and spleen (-4.5%, P =
      0.025) volumes and in chitotriosidase levels (-4.6%, P = 0.039) at 6 months were
      commensurately lower than those reported previously in an open-label trial using
      100 mg TID; hemoglobin and platelet counts were not boosted. At 12 months there
      were further mean decreases from baseline in liver volume (-6.2%, P = 0.037),
      spleen volume (-10.1%, P < 0.05), and chitotriosidase levels (-15.3%, P < 0.05)
      as well as mean changes of +1.2 and +14.7% in hemoglobin and platelet
      concentrations, respectively [correction]. There were no serious adverse effects
      throughout the 6-month study period; common side effects were diarrhea (94%) and
      weight loss (67%), comparable to the incidence in the original trial. We conclude
      that OGT 918 was safe and effective at 50 mg TID, but shows dose dependency in
      ameliorating parameters of Gaucher disease relative to the results noted in the
      seminal trial; there was no improvement in the rate of hematological response and
      no reduction in side effects. Results from the extension wherein some patients
      were dose increased suggest that 100 mg TID should be the preferred starting
      regimen for patients with symptomatic type I Gaucher disease.

PMID- 12064910
TI  - Limitations of a mouse model of sickle cell anemia.
AB  - We aimed to use an established murine model of sickle cell anemia to develop an
      unambiguous method for testing new therapies, with survival as an end point.
      Survival rates following various challenges were compared for three different
      groups of mice: (a) sickle cell mice expressing human hemoglobin-S exclusively
      ((h)beta(s)); (b) littermates that expressed both human hemoglobin S and murine
      beta major globin ((h)beta(s)(m)beta); and (c) wild-type C57BL/6 mice (wt). Two
      types of challenge were tested. The first set of studies was based upon recent
      observations indicating that granulocyte-colony stimulating factor (G-CSF) can
      precipitate severe complications in patients with sickle cell disease. While
      (h)beta(s) mice had higher neutrophil counts than (h)beta(s)(m)beta mice at
      baseline, (h)beta(s) mice tolerated several different doses and schedules of
      either human or murine G-CSF without adverse effects. A second type of challenge
      tested whether sickle cell mice exhibit an enhanced susceptibility to hemoglobin
      deoxygenation. Acute hemoglobin deoxygenation was accomplished either by a single
      intraperitoneal injection of sodium bisulfite or by a 1-h exposure to hypoxia.
      Neither intervention resulted in a significantly different survival rate for
      (h)beta(s) mice compared to either (h)beta(s)(m)beta or wt mice. Chronic twice
      weekly exposures to hypoxia (1 h per exposure) also failed to produce significant
      differences in survival rates between (h)beta(s) mice, (h)beta(s)(m)beta, and wt
      mice over a period of 12 weeks. Our results demonstrate that neither G-CSF
      administration nor hypoxia accentuates survival differences between this model of
      sickle cell mouse and normal controls.

PMID- 12064911
TI  - Sustained hypoglycemia affects glucose transporter expression of human blood
      leukocytes.
AB  - The scarce data available on leukocyte glucose transporter expression are
      contradictory and nothing is known about its regulation by glycemic state.
      Therefore, cytospin preparations of blood leukocytes were searched
      immunocytochemically for the high-affinity glucose transporters GLUT1, 3, and 4.
      Hypoglycemia-associated quantitative changes in transporter expression were
      assessed by flow cytometry. Granulocytes and monocytes stained for GLUT1, 3, and
      4. Granulocyte GLUT4 levels were increased by 73% (P < 0.05) under hypoglycemic
      conditions, which was paralleled by a reduction in GLUT1 and a rise in GLUT3. In
      monocytes, GLUT3 was elevated by 134% (P < 0.05), whereas GLUT1 and GLUT4
      remained unaffected upon hypoglycemia. Apart from a minor subpopulation,
      lymphocytes were negative for these carriers. In conclusion, GLUT1, 3, and 4 are
      abundantly expressed in granulocytes and monocytes. The differential response of
      individual isoforms to hypoglycemia may represent a mechanism to protect the
      cells from the stress of glucose deprivation.

PMID- 12064912
TI  - Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or
      MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells.
AB  - There is considerable interest among basic and clinical researchers in novel
      drugs with activity against leukemia. The vast history of experience of
      traditional Chinese medicine (TCM) with medicinal plants may facilitate the
      identification of novel antileukemic compounds. In the present investigation, we
      tested 22 drugs for their activity toward CCRF-CEM cell lines: artesunate,
      artemisinin, baicalein, baicalin, berberine, bufalin, cantharidin, cephalotaxine,
      curcumin, daidzein, daidzin, diallyl disulfide, ginsenoside Rh2, glycyrrhizic
      acid, isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin,
      quercetin, tannic acid, and tetrahydronardosinon. As compounds from folk
      medicinal remedies are sometimes looked upon as alternative medicine with some
      hesitation or criticism, we investigated only chemically pure compounds and
      tested the drugs independently in two different laboratories in Germany and
      Australia. We used CCRF-CEM parental cells and doxorubicin-selected P
      glycoprotein (P-gp)/MDR1-expressing CEM/ADR5000, vinblastine-selected P-gp/MDR1
      expressing CEM/VLB(100), and epirubicin-selected multidrug resistance-related
      protein 1 (MRP1)-expressing CEM/E1000 sublines thereof. While CEM/ADR5000,
      CEM/VLB(100), and CEM/E1000 cells were highly resistant to the corresponding
      selecting agents, no or only minimal degrees of cross-resistance were observed to
      TCM drugs in both growth inhibition assay and MTT assay (range from 0.4- to 8
      fold). Homoharringtonine, artesunate, and bufalin were most active among this
      panel of compounds. As shown by flow cytometry, artesunate significantly
      increased daunorubicin accumulation in CEM/E1000 cells, but not in CEM/VLB(100)
      or CCRF-CEM parental cells. Bufalin caused a small, but significant increase in
      daunorubicin accumulation in CEM/VLB(100) and CEM/E1000 cells. As artesunate and
      bufalin showed both antileukemic activity if applied alone and modulation
      activity in combination with daunorubicin in multidrug-resistant (MDR) cells,
      these two drugs may be suitable for novel combination treatment regimens to
      improve leukemia cell killing.

PMID- 12064914
TI  - The "ex vivo" patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and
      CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation
      states.
AB  - To define a dynamic sequence of phenotypic changes related to early and late
      phases of NK-cell activation, we have analyzed by four-color flow cytometry the
      immunophenotype of normal blood NK-cells from 12 healthy individuals and compared
      it with those from 15 patients with acute viral infections and 15 patients with
      either chronic infections or tumors. Although a great interindividual variability
      was found, nonstimulated CD56(+) NK-cells, present in normal blood samples,
      usually were CD2(-/+lo), CD7(+hi), HLA-DR(-), CD11b(+), CD38(+), CD11a(+hi),
      CD45RA(+hi), and CD45RO(-), the expression of CD11c and CD57 being heterogeneous
      and variable. Recently activated NK-cells, herein corresponding to NK-cells from
      patients with acute viral infections, displayed a pattern of expression of
      CD2/CD7 similar to that referred to above, but they typically showed higher
      levels of CD11a, CD38, and HLA-DR, as well as downregulation of CD11b and CD45RA,
      accompanied in some cases by coexpression of CD45RO; in addition, these NK-cells
      were CD11c(+) and CD57(-/+lo). Late-activated NK-cells, represented by NK-cells
      present in patients with chronic infections and tumors, converted into a
      CD2(+hi)/CD7(-/+lo) immunophenotype and expressed heterogeneously low levels of
      CD38 and CD11b; moreover, they were CD57(+) and CD11c(-/+). At this stage, most
      NK-cells had already reverted into their original CD45RA(+)/CD45RO(-)/HLA-DR(-)
      phenotype. In summary, we show that the patterns of expression of CD2/CD7,
      CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR may help us to define the
      immunophenotypic profiles associated with early and late NK-cell activation
      phases in 'in vivo' models.

PMID- 12064913
TI  - In vitro mass production of human erythroid cells from the blood of normal donors
      and of thalassemic patients.
AB  - We describe a new two-step culture method for mass production in vitro of
      erythroid cells from either CD34+ (10(5) cells/mL) or light-density (10(6)
      cells/mL) cells purified from the blood of normal donors and thalassemic
      patients. The method includes (i) culture of the cells in the presence of
      dexamethasone and estradiol (10(-6) M each) and (ii) the growth factors SCF (50
      ng/mL), IL-3 (1 ng/mL), and EPO (1 U/mL). In their proliferative phase, these
      cultures generated approximately 1.2 x 10(7) erythroblasts for each milliliter of
      blood collected from normal donors or thalassemic patients. They were composed
      mostly (90%) of CD45(low)/glycophorin (GPA)(neg)/CD71(1ow) cells at day 7, 50
      60?% of which became CD45(neg)/GPA+/CD71high by days 15-20. However, when cells
      from days 7 to 12 of the proliferative phase were transferred in differentiation
      medium containing EPO and insulin, they progressed to mature erythroblasts (g90%
      benzidine(pos) and CD45(neg)/GPA+/CD71medium) in 4 days. Because of the high
      number of erythroid cells that are generated from modest volumes of blood, this
      method will prove useful in donor-specific studies of erythroid differentiation.

PMID- 12064915
TI  - Polymorphisms in the 5' flanking region of the HFE gene: linkage disequilibrium
      and relationship to iron homeostasis.
AB  - We have discovered two single-nucleotide polymorphisms in the 5' flanking region
      of the HFE gene. These mutations are -970 T-->G and -467 C-->G, numbering from
      the ATG start codon. When a T was present at -970, a C was always found at -467.
      The C allele was the less common at nt -467 with a gene frequency of 0.31 in
      white subjects with wild-type HFE. Slightly lower gene frequencies were observed
      in a small number of Hispanic and African-American subjects and a slightly higher
      frequency in a few Asian subjects. The less common -467 mutation was found in
      almost 12 chromosomes that bore the 845G-->A (C282Y) mutation and was
      significantly more prevalent in chromosomes containing the 187C-->G (H63D)
      mutation. Although this mutation is near an HNF3B/HFH2 site, its presence did not
      seem to affect iron metabolism as judged by the serum ferritin or transferrin
      saturation levels. The tighter association of the -467 polymorphism with the
      C282Y mutation is consistent with other data that suggest that the C282Y mutation
      has occurred relatively recently and that the H63D mutation is considerably
      older.

PMID- 12064917
TI  - Correlation of bone marrow response with hematological, biochemical, and visceral
      responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher
      disease in 30 adult patients.
AB  - PURPOSE: This investigation correlates the marrow response with the degree of
      increase in hemoglobin (Hb) and platelet count (Plt); decrease in concentrations
      of plasma tartrate-resistant acid phosphatase, serum angiotensin-converting
      enzyme (ACE), serum ferritin, and plasma chitotriosidase; and decrease in liver
      and spleen size, measured by ultrasonography. METHODS: Thirty adult patients with
      nonneuronopathic (type 1) Gaucher disease (23% splenectomized) were followed for
      mean periods of 12 and 36 months. RESULTS: The series achieved highly significant
      mean responses in all hematological, biochemical, and visceral parameters over
      both observation periods; over a mean 36 months, 19 (63%) had a marrow response,
      11 (37%) did not. Six of 7 splenectomized patients attained a marrow response.
      There were no significant differences between the marrow responders and
      nonresponders in age, sex, spleen status, Gaucher genotype distribution, mean
      baseline hematological or biochemical values or liver size, or mean follow-up. At
      a mean follow-up of 12 months, no significant differences yet were evident
      between marrow responders and nonresponders in seven of eight response
      parameters, but marrow responders had a significantly greater reduction in plasma
      chitotriosidase and a trend toward significantly greater reduction in serum ACE.
      At a mean follow-up of 36 months, marrow responders had a significantly greater
      mean increase in Plt and mean decrease in serum ferritin concentration and liver
      size than did marrow nonresponders; the trend toward greater ACE reduction in
      marrow responders deepened. However, chitotriosidase response now was equivalent
      in both subgroups. Marrow nonresponders had a significantly greater mean
      diminution in spleen size than did marrow responders, but the marrow
      nonresponders had significantly larger mean spleen size at baseline. Marrow
      nonresponders also had a greater mean increase in Hb than did marrow responders,
      but the difference was not significant. The two subgroups had equivalent mean
      reductions of plasma TRAP. CONCLUSIONS: The clinical relevance of qualitative MRI
      of the bone marrow in monitoring patients receiving ERT for nonneuronopathic
      Gaucher disease show that marrow nonresponders can derive considerable benefit
      from ERT across a variety of other response parameters and suggest an influence
      of spleen size on marrow response to ERT.

PMID- 12064916
TI  - Deferiprone versus deferoxamine in patients with thalassemia major: a randomized
      clinical trial.
AB  - Deferiprone has been suggested as an effective oral chelation therapy for
      thalassemia major. To assess its clinical efficacy, we compared deferiprone with
      deferoxamine in a large multicenter randomized clinical trial. One-hundred forty
      four consecutive patients with thalassemia major and serum ferritin between 1500
      and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or
      deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was
      the reduction of serum ferritin. Liver and heart iron contents were assessed by
      magnetic resonance. Liver iron content and fibrosis stage variations were
      assessed on liver biopsy by the Ishak score in all patients willing to undergo
      liver biopsy before and after treatment. The mean serum ferritin reduction was
      222 +/- 783 ng/ml in the deferiprone and 232 +/- 619 ng/ml in the deferoxamine
      group (P = 0.81). No difference in the reduction of liver and heart iron content
      was found by magnetic resonance between the two groups. Thirty-six patients
      accepted to undergo repeat liver biopsy: 21 in the deferiprone and 15 in the
      deferoxamine group. Their mean reduction of liver iron content was 1022 +/- 3511
      microg/g of dry liver and 350 +/- 524, respectively (P = 0.4). No difference in
      variation of the Ishak fibrosis stage was observed between the two groups.
      Treatment was discontinued because of reversible side effects in 5 patients in
      the deferiprone group (3 hypertransamin/asemia and 2 leukocytopenia) and in none
      in the deferoxamine group. These findings suggest that deferiprone may be as
      effective as deferoxamine in the treatment of thalassemia major with few mild and
      reversible side effects.

PMID- 12064919
TI  - Expression of factor VIII in recombinant and transgenic systems.
AB  - Deficiency in a coagulation factor VIII (FVIII) causes a genetic disorder
      hemophilia A, which is treated by repeated infusions of expensive FVIII products.
      Recombinant FVIII (rFVIII), the culmination of years of extensive international
      research, is an important alternative to plasma-derived FVIII (pdFVIII) and is
      considered to have a higher margin of safety. Advances in biotechnology allowed
      production of rFVIII at industrial scale, which significantly improved treatment
      of hemophilia A patients. We review the contemporary methods used for FVIII
      expression in mammalian cell culture systems and discuss the factors responsible
      for insufficient recoveries of rFVIII, such as inefficient accumulation of FVIII
      mRNA in the cell, complexity of the mechanisms of FVIII secretion, and
      instability of secreted FVIII. The approaches to improve the yield of rFVIII in
      cell culture systems include genetic engineering of B-domain-deleted FVIII,
      introduction of introns into FVIII cDNA constructs for more efficient processing
      and accumulation of FVIII mRNA, and introduction of mutations into chaperone
      binding sites of FVIII to improve its secretion. Design of FVIII with prolonged
      half-life in vivo is considered as another promising direction in improving
      rFVIII protein and efficiency of hemophilia A therapy. As an alternative to
      expression of rFVIII in cell culture systems, we discuss production of rFVIII in
      transgenic animals, where high levels of rFVIII have been successfully secreted
      into milk. We also pay attention to the major limitations of this approach, such
      as safety issues associated with potential transmission of animal pathogens.
      Finally, we present a brief characterization of commercial recombinant FVIII
      products currently available on the market for hemophilia A treatment.

PMID- 12064918
TI  - Inhibition of Smad5 in human hematopoietic progenitors blocks erythroid
      differentiation induced by BMP4.
AB  - Patients with secondary myelodysplasias and acute myeloid leukemias (MDS/AML)
      frequently exhibit interstitial deletions of the chromosome-5q resulting in
      hemizygous loss of the transcription transactivator Smad5. Smad5 is a member of
      the signal transducer family conveying the pleiotropic TGF-gb/BMP cytokine
      signals with roles in development, cell growth control, and tumor progression.
      Here we present a study of the Smad5 expression and its functional role in
      leukemia cell lines as well as in primary CD34+ progenitors of MDS/AML patients
      and healthy individuals. Consistent Smad5 gene expression in these cell types and
      the gradual increase in its mRNA and protein levels in a model of induced
      erythroid differentiation of murine erythroleukemia (MEL) cells suggest a role of
      the gene in hematopoiesis. We show that bone morphogenetic protein 4 (BMP4)
      directs Smad5 activation in human hematopoietic cells, as monitored at the levels
      of protein phosphorylation, nuclear translocation, and specific transcription
      response. In vitro induction of normal human CD34+ cells by BMP4 results in
      significantly increased proliferation of erythroid progenitors (BFU-E) and
      formation of glycophorin-A+ cells, whereas perturbation of Smad5 expression by
      antisense oligonucleotides causes significantly decreased rates of BMP4-induced
      erythroid differentiation. We have not detected any effects of Smad5 inhibition
      on BMP4-stimulated progenitors of the granulocyteNmacrophage lineage. We propose
      that the BMP4/Smad5 signal transduction pathway activates hematopoietic
      differentiation programs that may be impaired in anemia manifestations in MDS and
      AML patients with Smad5 haploinsufficiency.

PMID- 12064920
TI  - Glucose-6-phosphate dehydrogenase deficiency in Portugal: biochemical and
      mutational profiles, heterogeneity, and haplotype association.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human
      enzymopathy. This deficiency in erythrocytes has a prevalence of 0.51 +/- 0.109
      in the Caucasoid male population of Portugal. The frequency for deficiency
      conferring genes is 0.39% in the Portuguese population. In the herein study
      populations males from areas of Portugal presenting with the highest prevalence
      of G6PD deficiency (Castelo Branco, Setubal, Faro, and Lisbon) as well as similar
      subjects located in the border Center/North area of the country (Viseu) have been
      analyzed for biochemical parameters and screened for mutations and haplotype
      associated mutations commensurate with G6PD deficiency. Six intragenic
      restriction fragment length polymorphisms (RFLPs) were studied: exon 5, nt 376 A 
      ->G, FokI; intron 5, nt 611 C--> G, PvuII; intron 8, nt 163 C--> T, BspHI; exon
      10, nt 116 G --> A, PstI; exon 11, nt 1311 C--> T, BclI; and intron 11, nt 93 T -
      >C, NlaIII. New haplotypes were constructed with the inclusion of intron 11, nt
      93 T--> C, NlaIII, and only 5 of 64 possible haplotypes were found to show a
      marked linkage disequilibrium for several RFLPs and also for mutations and
      specific haplotypes. The control population (n = 168 males) presented the G6PD B
      variant and corresponded to haplotypes I (- - + + - -), Ia (- - + + - +), and
      VIIa (- - + + + +), in 91.8, 2.3, and 5.9%, respectively. The PCR and sequencing
      analysis of extracted DNAs from the deficient G6PD group showed 48.6% (16/33) of
      individuals with the G6PD A- mutation, corresponding to haplotype VIa (+ + - + -
      +); 9% (3/33) with the Betica mutation and 18% (6/33) with the Santa Maria
      mutation, both of them associated with haplotype IVa (+ - - + ?- +); 6.1% (2/33)
      with the Mediterranean mutation associated with haplotype VIIa; 12.3% (4/33) with
      the Seattle mutation, 3.0% (1/33) with Gaohe mutation; and a new mutation, 3.0%
      (1/33), which we designated by G6PD Flores, all of them associated with haplotype
      I.

PMID- 12064921
TI  - Surface antigen changes during normal neutrophilic development: a critical
      review.
AB  - Neutrophil surface molecules function in part as biological sensors. Surface
      antigens undergo several changes during neutrophilic maturation to accommodate
      the cell's function. Surface antigens may appear with neutrophilic maturation,
      such as CD16b, CD35, and CD10; disappear with maturation, such as CD49d and CD64;
      be maintained during maturation, such as CD32, CD59, and CD82; or disappear with
      maturation but reappear after neutrophilic extravasation, such as CD49b. This
      article reviews the alterations in surface antigen expression during normal
      neutrophilic granulopoiesis.

PMID- 12064922
TI  - Conserved, erythropoietin-responsive VL30 promoters isolated from erythroid
      progenitor cells.
AB  - Virus-like 30S (VL30) elements are endogenous retro-elements of the mouse
      retrotransposon family. These elements are transcriptionally responsive in a
      temporal and tissue-specific manner due to the U3 promoter region of the
      elements' long terminal repeat (LTR). We have analyzed VL30 promoters from
      erythroid progenitor cell lines (MEL 585S and ELM-I-1) that contrasted in their
      response to erythropoietin (epo). Through RT-PCR-generated cDNAs, VL30 promoters
      were identified and showed homology to the third and fourth U3 subgroups, with
      GATA-1, Jak2/STAT5, and B10 RRE sites. One clone (ELM5) showed 97% homology to
      BVL-1, a putative epo-responsive VL30 element. In addition, a novel U3 promoter
      (MEL/ELM CONSTIT) showed complete sequence homology between both cell lines.
      Ribonuclease protection confirmed that epo-induced VL30 promoters were activated
      in ELM-I-1 cells, whereas the conserved VL30 MEL-ELM CONSTIT VL30 promoter showed
      no enhanced expression in the epo-unresponsive MEL cells. Identification of these
      U3 promoters suggests that VL30s are conserved and can be transcriptionally
      activated in an epo-specific manner.

PMID- 12064923
TI  - Amelioration of painful crises in sickle cell disease by venesections.
AB  - Sickle cell disease patients who acquire iron deficiency may experience a degree
      of amelioration from painful crises in terms of frequency, severity, and
      duration. This observation prompted us to identify the potential utility of iron
      load reduction in the management of this disease. Thirteen sickle cell patients
      not ameliorated by conventional treatment entered a weekly venesection protocol.
      Hematological values and painful crises of all degrees of severity were recorded
      and compared to those of the last 12 months before venesection for each case
      separately ("historical controls"). A decrease was noted in the frequency and
      intensity of several types of painful crises. Reduction of iron load by
      venesection seems to be a simple, safe, side-effect-free, and efficient way of
      preventing and ameliorating to a large extent painful crises in sickle cell
      disease. The biological effects of venesection on other parameters of sickle cell
      disease remain to be determined.

PMID- 12064924
TI  - Decreased bone density in splenectomized Gaucher patients receiving enzyme
      replacement therapy.
AB  - Little is known about the effect of enzyme replacement therapy (ERT) on the bone
      abnormalities in Gaucher disease. Splenectomized Gaucher patients tend to suffer
      the most severe skeletal complications. We hypothesized that vitamin D
      supplementation would act synergistically with glucocerebrosidase infusions to
      increase bone density in splenectomized Gaucher patients. In a 24-month study, 29
      splenectomized Gaucher patients were randomized to three groups: Group 1,
      calcitriol (1,25-dihydroxyvitamin D3; 0.25-3.0 microg/day) alone for the first 6
      months with the addition of ceredase/cerezyme at 60 IU/kg every 2 weeks during
      months 7-12; Group 2, calcitriol together with ceredase/cerezyme at 60 IU/kg
      every 2 weeks during months 1-6; and Group 3, enzyme only at 60 IU/kg body wt
      every 2 weeks. In all three groups, enzyme dose was halved after the first 6
      months of therapy. The primary outcome measure was bone mineral density of the
      lumbar spine measured by single-energy quantitative CT. Bone density by single
      energy CT (P = 0.001) and by dual-energy CT (P = 0.06) declined overall, but
      there was no significant difference between the groups. Calcitriol had no
      significant effect on bone density. Fat fraction in lumbar spine increased (P =
      0.000) and skeletal MRI scores improved. Bone-specific alkaline phosphatase (P =
      0.002) and serum osteocalcin increased (P = 0.008), while blood cyclic AMP and
      urinary deoxypyridinoline did not change appreciably. Hemoglobin, platelet
      counts, and liver volume significantly improved. We conclude that ERT alone, or
      in combination with calcitriol, cannot repair the bone composition in
      splenectomized adult Gaucher patients. Alternatively, measuring trabecular bone
      density may be an inadequate marker of clinical efficacy for treating skeletal
      involvement in Gaucher disease.

PMID- 12064925
TI  - Juvenile hemochromatosis in a Spanish family.
AB  - Juvenile hemochromatosis (JH) is a characteristic form of genetic hemochromatosis
      with an early onset and severe clinical course leading to death if iron depletion
      treatment is not timely applied. Clinical complications include liver cirrhosis,
      heart failure, hypogonadotropic hypogonadism, and diabetes. In the present study
      we report the first case of JH described in Spain. Biochemical and genetic
      characteristics of the patient and relatives (parents and siblings) were
      investigated. No individual presented either the mutation at position 845 of the
      HFE gene or at position 750 of the TFR2 gene, associated with other types of
      hemochromatosis. Nevertheless, some individuals were homozygous for the mutation
      at position 187 of HFE. The hypothetic region of association with JH, located at
      chromosome 1q, was also investigated and results show that the patient presented
      a unique genotypic combination in 1q. The only brother with heavy iron deposits
      in hepatocytes was found to be heterozygous for the JH-associated region and
      homozygous for the HFE187 gene, suggesting a synergistic effect between both
      hemochromatosis-associated genes.

PMID- 12064928
TI  - A switch in disulfide linkage during minicollagen assembly in hydra nematocysts
      or how to assemble a 150-bar-resistant structure.
AB  - Hydra minicollagen, the shortest collagen known, is an important component of the
      nematocyst wall, which has a very high tensile strength. It has an unusual
      structure, with small and closely related Cys-rich domains at both ends of its
      chains. Three chains are trimerized by a central collagenous domain.
      Polyhydroxyproline helices connect the Cys-rich domains with the collagenous
      domain. The minicollagen precursor contains three internal disulfide bridges in
      each Cys-rich domain and no disulfide bridges between chains of the same trimeric
      molecule or between different molecules. Biochemical and structural evidence as
      well as confocal immunofluorescence microscopy points to disulfide-mediated
      assembly during maturation of nematocysts.

PMID- 12064927
TI  - Building collagen molecules, fibrils, and suprafibrillar structures.
AB  - Fibril-forming collagens are synthesized in precursor form, procollagens, with N-
      and C-terminal propeptide extensions. The C-propeptides direct chain association
      during intracellular assembly of the procollagen molecule from its three
      constituent polypeptide chains. Following or during secretion into the
      extracellular matrix, propeptides are cleaved by specific procollagen
      proteinases, thereby triggering fibril formation. The recent determination of the
      low-resolution structure of the C-propeptide trimer gives insights into the
      mechanism of procollagen chain association. In the extracellular matrix, the
      procollagen C-propeptides ensure procollagen solubility, while persistence of the
      N-propeptides controls fibril shape. Mechanisms for the control of fibril
      diameter are reviewed in terms of the radial packing model for collagen fibril
      structure. Finally, procollagen molecules have recently been shown to undergo
      liquid crystalline ordering in solution, prior to fibril assembly. This may
      provide an explanation for the liquid crystal-like suprafibrillar architectures
      of different connective tissues.

PMID- 12064929
TI  - Structure of type I and type III heterotypic collagen fibrils: an X-ray
      diffraction study.
AB  - The molecular packing arrangement within collagen fibrils has a significant
      effect on the tensile properties of tissues. To date, most studies have focused
      on homotypic fibrils composed of type I collagen. This study investigates the
      packing of type I/III collagen molecules in heterotypic fibrils of colonic
      submucosa using a combination of X-ray diffraction data, molecular model
      building, and simulated X-ray diffraction fibre diagrams. A model comprising a 70
      nm-diameter D- (approximately 65 nm) axial periodic structure containing type I
      and type III collagen chains was constructed from amino acid scattering factors
      organised in a liquid-like lateral packing arrangement simulated using a
      classical Lennard-Jones potential. The models that gave the most accurate
      correspondence with diffraction data revealed that the structure of the fibril
      involves liquid-like lateral packing combined with a constant helical inclination
      angle for molecules throughout the fibril. Combinations of type I:type III
      scattering factors in a ratio of 4:1 gave a reasonable correspondence with the
      meridional diffraction series. The attenuation of the meridional intensities may
      be explained by a blurring of the electron density profile of the D period caused
      by nonspecific or random interactions between collagen types I and III in the
      heterotypic fibril.

PMID- 12064930
TI  - Collagen fibril formation in a wound healing model.
AB  - Control of tissue composition and organization will be a key feature in the
      development of successful products through tissue engineering. However, the
      mechanism of collagen fibril formation, growth, and organization is not yet fully
      understood. In this study we have examined collagen fibril formation in a wound
      healing model in which the newly formed fibrils were kept distinct from
      preexisting tissue through use of a porous tubular biomaterial implant. Samples
      were examined after 4, 6, 14, and 28 days by light microscopy, in situ
      hybridization, and immunofluorescence microscopy. These showed a normal wound
      healing response, with significant collagen formation at 14 and 28 days.
      Individual collagen fibrils were isolated from these samples by gentle extraction
      in a gentamicin-containing buffer which allowed extraction of a large proportion
      of intact fibrils. Examination by transmission electron microscopy showed that
      approximately 80% of the intact fibrils showed a single polarity reversal, with
      both ends of each fibril comprising collagen amino-terminal domains; the
      remaining fibrils had no polarity reversal. All fibrils had similar diameters at
      both time points. Immunoelectron microscopy showed that all labeled fibrils
      contained both type I and III collagens. These data indicate that this wound
      healing model provides a system in which collagen fibril formation can be readily
      followed.

PMID- 12064931
TI  - Analysis of the collagen VI assemblies associated with Sorsby's fundus dystrophy.
AB  - Age-related macular degeneration is the leading cause of blindness in the Western
      world, and the pathophysiology of the condition is largely unknown. However, it
      shares many clinical and pathological features with Sorsby's fundus dystrophy
      (SFD), an autosomal dominant disease, known to be associated with mutations in
      the TIMP-3 gene. In Bruch's membrane of both conditions, there are molecular
      assemblies with distinct transverse bands occurring with a periodicity of about
      100 nm. Similar assemblies were also found in the vitreous of a patient with full
      thickness macular holes and were identified as being made of collagen VI. The
      assemblies found in the eye with SFD can be classified into two types, both with
      a 105-nm axial repeat, but one showing pairs of narrow bands about 30 nm apart
      and the other showing a single broad band in every repeat. By comparison with the
      assemblies in the vitreous, collagen VI is considered to be the most likely
      protein in these assemblies. Furthermore, both of the assemblies associated with
      SFD can be explained in terms of collagen VI tetramers, one in which the
      tetramers bind to the mutant tissue inhibitor of metalloproteinases-3 (the gene
      product of TIMP-3) and the other in which little or no binding occurs. TIMP-3
      bound to collagen VI may be more resistant to degradation and create an imbalance
      between the normal amount of TIMP-3 and matrix metalloproteinases (the substrate
      of TIMPs) in Bruch's membrane with consequent disruption of the normal metabolic
      processes. Understanding the structure of these collagen VI/TIMP assemblies in
      Bruch's membrane may prove to be important for understanding the pathophysiology
      of age-related macular degeneration.

PMID- 12064932
TI  - Generalized Crick equations for modeling noncanonical coiled coils.
AB  - Crick envisaged the alpha-helical coiled coil to result from systematic bending
      of an alpha-helix such that every seventh residue was structurally equivalent,
      and he derived equations for the coordinates of the backbone atoms. Crick's
      predictions were vindicated experimentally and coiled-coil sequences were shown
      to have hydrophobic residues alternately spaced 3 and 4 residues apart.
      Nonetheless, in some coiled coils such canonical heptad repeats are interrupted
      by inserts of 3 or 4 residues generating decad and hendecad motifs. The
      supercoiling of the coiled coils varies with the sequence pattern, being left- or
      right-handed in purely heptad-based or hendecad-based motifs, respectively. To
      model coiled coils with a mixture of motifs, we describe how Crick's equations
      can be modified for cases where the pitch is not constant. Using the analogy of
      the bending of a beam, we took the tilt angle to change linearly with distance
      along the major helix and the pitch of a motif to be affected by neighboring
      motifs depending on the rigidity of the alpha-helical strands. We tested our
      approach by fitting the two-, three-, and four-stranded noncanonical coiled coils
      of GrpE, hemagglutinin, and tetrabrachion. The backbone atoms of the model and
      crystal structures agreed with root mean square deviations of <1.1 A.

PMID- 12064933
TI  - Analysis of alpha-helical coiled coils with the program TWISTER reveals a
      structural mechanism for stutter compensation.
AB  - Alpha-helical coiled coils represent a widespread protein structure motif
      distinguished by a seven-residue periodicity of apolar residues in the primary
      sequence. A characteristic "knobs-into-holes" packing of these residues into a
      hydrophobic core results in a superhelical, usually left-handed, rope of two or
      more alpha-helices. Such a geometry can be parameterized. For this purpose, a new
      computer program, TWISTER, was developed. With the three-dimensional coordinates
      as input, TWISTER uses an original algorithm to determine the local coiled-coil
      parameters as a function of residue number. In addition, heptad positions are
      assigned based on structural criteria. It is known that frequently encountered
      discontinuities in the heptad repeat, such as stutters and skips, can be
      tolerated within a continuous coiled coil but result in a local distortion of its
      geometry. This was explored in detail with the help of TWISTER for several two-
      and three-stranded coiled coils. Depending on the particular protein, stutters
      were found to be compensated locally by an unwinding of the superhelix, alpha
      helical unwinding, or both. In the first case, there is often a local switch from
      a left-handed to a right-handed superhelix. In general, the geometrical
      distortion is confined to about two alpha-helical turns at either side of the
      stutter. Furthermore, stutters result in a local increase of the coiled-coil
      radius.

PMID- 12064934
TI  - Removing an interhelical salt bridge abolishes coiled-coil formation in a de novo
      designed peptide.
AB  - Alpha-helical coiled coils represent a common protein oligomerization motif that
      are mainly stabilized by hydrophobic interactions occurring along their coiled
      coil interface, the so-called hydrophobic seam. We have recently de novo designed
      and optimized a series of two-heptad repeat long coiled-coil peptides which are
      further stabilized by a complex network of inter- and intrahelical salt bridges.
      Here we have extended the de novo design of such two heptad-repeat long peptides
      by removing the central and most important g-e' Arg to Glu (g-e'RE) ionic
      interhelical interaction and replacing these residues by alanine residues. The
      effect of the missing interhelical ionic interaction on coiled-coil formation and
      stability has been analyzed by CD spectroscopy, analytical ultracentrifugation,
      and X-ray crystallography. We show that the peptide, while being highly alpha
      helical, is no longer able to form a parallel coiled-coil structure but rather
      assumes an octameric globular helical assembly devoid of any coiled-coil
      interactions.

PMID- 12064935
TI  - Investigating the tolerance of coiled-coil peptides to nonheptad sequence
      inserts.
AB  - Coiled-coil motifs foster a wide variety of protein-protein interactions.
      Canonical coiled coils are based on 7-residue repeats, which guide the folding
      and assembly of amphipathic alpha-helices. In many cases such repeats remain
      unbroken for tens to hundreds of residues. However, the sequences of an
      increasing number of putative and characterised coiled coils digress from this
      pattern. We probed the consequences of nonheptad inserts using a designed leucine
      zipper system. The parent peptide, SKIP0, which had four contiguous heptads, was
      confirmed as a parallel homodimer by circular dichroism spectroscopy and
      analytical ultracentrifugation. Seven daughter peptides were constructed in which
      1 to 7 alanine residues were inserted between the central heptads of SKIP0. Like
      SKIP0, SKIP7 formed a stable helical dimer, but the other peptides were highly
      destabilised, with the order of dimer stability SKIP4 >> SKIP5 > SKIP6 > SKIP3 >
      SKIP2 > SKIP1. These results are consistent with an extended theory of coiled
      coil assembly in which coiled-coil-compatible motifs are based on 3- and 4
      residue spacings and most notably heptad (7-residue) and hendecad (11-residue)
      repeats. Thus, they help explain why in natural sequences, inserts after
      canonical heptad repeats most commonly comprise 4 residues. Possible biological
      roles for nonheptad inserts are discussed.

PMID- 12064936
TI  - Characterization of early assembly intermediates of recombinant human keratins.
AB  - The intermediate filaments (IFs) form major structural elements of the
      cytoskeleton. In vitro analyses of these fibrous proteins reveal very different
      assembly properties for the nuclear and cytoplasmic IF proteins. However,
      keratins in particular, the largest and most heterogenous group of cytoplasmic IF
      proteins, have been difficult to analyze due to their rapid assembly dynamics
      under the near-physiological conditions used for other IF proteins. We show here
      that keratins, like other cytoplasmic IF proteins, go through a stage of
      assembling into full-width soluble complexes, i.e., "unit-length filaments"
      (ULFs). In contrast to other IF proteins, however, longitudinal annealing of
      keratin ULFs into long filaments quasi-coincides with their formation. In vitro
      assembly of IF proteins into filaments can be initiated by an increase of the
      ionic strength and/or lowering of the pH of the assembly buffer. We now document
      that 23-mer peptides from the head domains of various IF proteins can induce
      filament formation even under conditions of low salt and high pH. This suggests
      that the "heads" are involved in the formation and longitudinal association of
      the ULFs. Using a Tris-buffering protocol that causes formation of soluble
      oligomers at pH 9, the epidermal keratins K5/14 form less regular filaments and
      less efficiently than the simple epithelial keratins K8/18. In sodium phosphate
      buffers (pH 7.5), however, K5/14 were able to form long partially unraveled
      filaments which compacted into extended, regular filaments upon addition of 20 mM
      KCl. Applying the same assembly regimen to mutant K14 R125H demonstrated that
      mutations causing a severe disease phenotype and morphological filament
      abnormalities can form long, regular filaments with surprising efficiency in
      vitro.

PMID- 12064937
TI  - A role for the 1A and L1 rod domain segments in head domain organization and
      function of intermediate filaments: structural analysis of trichocyte keratin.
AB  - A dynamic model is proposed to explain how the 1A and linker L1 segments of the
      rod domain in intermediate filament (IF) proteins affect the head domain
      organization and vice versa. We have shown in oxidized trichocyte IF that the
      head domain sequences fold back over and interact with the rod domain. This
      phenomenon may occur widely in reduced IF as well. Its function may be to
      stabilize the 1A segments into a parallel two-stranded coiled coil or something
      closely similar. Under differing reversible conditions, such as altered states of
      IF assembly, or posttranslational modifications, such as phosphorylation etc.,
      the head domains may no longer associate with the 1A segment. This could
      destabilize segment 1A and cause the two alpha-helical strands to separate.
      Linker L1 would thus act as a hinge and allow the heads to function over a wide
      lateral range. This model has been explored using the amino acid sequences of the
      head (N-terminal) domains of Type I and Type II trichocyte keratin intermediate
      filament chains. This has allowed several quasi-repeats to be identified. The
      secondary structure corresponding to these repeats has been predicted and a model
      has been produced for key elements of the Type II head domain. Extant disulfide
      cross-link data have been used as structural constraints. A model for the head
      domain structure predicts that a twisted beta-sheet region may wrap around the 1A
      segment and this may reversibly stabilize a coiled-coil conformation for 1A. The
      evidence in favor of the swinging head model for IF is discussed.

PMID- 12064938
TI  - Cryo-electron microscopy of trichocyte (hard alpha-keratin) intermediate
      filaments reveals a low-density core.
AB  - Trichocyte intermediate filaments (IF) are the principal components of epidermal
      appendages such as hair and nail. Based on studies by a variety of techniques, it
      has been inferred that trichocyte IF are structurally similar to other kinds of
      IF. However, some basic structural attributes have yet to be established: in
      particular, it has remained unclear whether IF are hollow. We have examined
      trichocyte IF isolated from rat vibrissae and human hair follicles by electron
      microscopy. Scanning transmission electron microscopy of freeze-dried specimens
      yielded mass-per-unit-length values of approximately 32 kDa/nm, with the human
      preparations also containing filaments at half this density, corresponding to two
      rather than four protofibrils. Radial density profiles calculated from cryo
      electron micrographs of vitrified specimens preserved in a near-native state
      revealed a low-density region of approximately 3 nm diameter around the filament
      axis. A minor species of filament with the same internal structure was surface
      decorated with material arranged with a helical pitch length of 9.3 nm. These
      filaments appear to represent IF coated with associated proteins-perhaps, "high
      sulfur" proteins-readied for incorporation into the filament-matrix biocomposite
      of the mature hair.

PMID- 12064940
TI  - Sequence comparisons of intermediate filament chains: evidence of a unique
      functional/structural role for coiled-coil segment 1A and linker L1.
AB  - A comprehensive analysis of the sequences of all types of intermediate filament
      chains has been undertaken with a particular emphasis on those of segment 1A and
      linker L1. This has been done to assess whether structural characteristics can be
      recognized in the sequences that would be consistent with the role of each region
      in the recently proposed "swinging head" hypothesis. The analyses show that
      linker L1 is the most flexible rod domain region, that it is the most elongated
      structure (on a per residue basis), and that it is the most variable region as
      regards sequence and length. Segment 1A has one of the two most highly conserved
      regions of sequence in the rod domain (the other being at the end of segment 2B),
      with seven particular residues conserved across all chain types. It also contains
      one of the very few potential interchain ionic interactions that could be
      conserved across all chain types. However, the aggregation of chains in segment
      1A is specified less precisely overall by interchain ionic interactions than are
      the other coiled-coil segments. The apolar residue contents in positions a and d
      of the heptad substructure are the highest of any coiled-coil segment in the
      intermediate filament family. Segment 1A also displays an amino acid composition
      atypical of not only coiled-coil segments 1B and 2B, but indeed of two-stranded
      coiled coils in general. Nonetheless, molecular modeling based on the crystal
      structure of the monomeric 1A fragment from human vimentin shows that coiled-coil
      formation is plausible. The most extensive regions of apolar/aromatic residues
      lie at the C-terminal end of segment 2B in the helix termination motif and in
      segment 1A in and close to the helix initiation motif. The predicted stability of
      the individual alpha-helices in segment 1A is greater than in those comprising
      segments 1B and 2B, though potential intrachain ionic interactions are either
      lacking or are minimal in number. Analysis of the 1A sequence and those regions
      immediately N- and C-terminal to it has shown that the capping residues are near
      optimal close to the previously predicted ends, thus adding to the likely
      stability of the alpha-helical structure. However, a second terminating sequence
      is predicted in 1A (about 10 residues back from the C-terminus). This allows the
      possibility of some unwinding of the alpha-helical structure of 1A immediately
      adjacent to linker L1 when the head domains no longer stabilize the coiled-coil
      structure. All of these data are consistent with the concept of a flexible hinge
      at L1 and with the ability of the two alpha-helical coiled-coil strands to
      separate under appropriate conditions and partly unwind at their C-terminal ends
      to allow the head domains a greater degree of mobility, thus facilitating
      function.

PMID- 12064939
TI  - Molecular dissection of the interaction of desmin with the C-terminal region of
      nebulin.
AB  - In vertebrate skeletal muscle, ultrastructural studies have suggested that the Z
      line and extracellular intermediate filaments are linked, although a structural
      basis for this has remained elusive. We searched for potential novel ligands of
      the Z-line portion of nebulin by a yeast two-hybrid (Y2H) approach. This
      identified that the nebulin modules M160 to M170 interact with desmin. In desmin,
      deletion series experiments assigned a 19-kDa central coiled-coil domain as the
      nebulin-binding site. The specific interactions of nebulin and desmin were
      confirmed in vitro by GST pull-down experiments. In situ, the nebulin modules
      M176 to M181 colocalize with desmin in a Z-line-associated, striated pattern as
      shown by immunofluorescence studies. Our data are consistent with a model that
      desmin attaches directly to the Z-line through its interaction with the nebulin
      repeats M163-M170. This interaction may link myofibrillar Z-discs to the
      intermediate filament system, thereby forming a lateral linkage system which
      contributes to maintain adjacent Z-lines in register.

PMID- 12064941
TI  - Fate of the nuclear lamina during Caenorhabditis elegans apoptosis.
AB  - Invertebrates and in Drosophila, lamins and lamin-associated proteins are primary
      targets for cleavage by caspases. Eliminating mammalian lamins causes apoptosis,
      whereas expressing mutant lamins that cannot be cleaved by caspase-6 delay
      apoptosis. Caenorhabditis elegans has a single lamin protein, Ce-lamin, and a
      caspase, CED-3, that is responsible for most if not all somatic apoptosis. In
      this study we show that in C. elegans embryos induced to undergo apoptosis Ce
      lamin is degraded surprisingly late. In such embryos CED-4 translocated to the
      nuclear envelope but the cytological localization of Ce-lamin remained similar to
      that in wild-type embryos. TUNEL labeling indicated that Ce-lamin was degraded
      only after DNA is fragmented. Ce-lamin, Ce-emerin, or Ce-MAN1 were not cleaved by
      recombinant CED-3, showing that these lamina proteins are not substrates for CED
      3 cleavage. These results suggest that lamin cleavage probably is not essential
      for apoptosis in C. elegans.

PMID- 12064942
TI  - 3D Structure of fish muscle myosin filaments.
AB  - Myosin filaments isolated from goldfish (Carassius auratus) muscle under relaxing
      conditions and viewed in negative stain by electron microscopy have been
      subjected to 3D helical reconstruction to provide details of the myosin head
      arrangement in relaxed muscle. Previous X-ray diffraction studies of fish muscle
      (plaice) myosin filaments have suggested that the heads project a long way from
      the filament surface rather than lying down flat and that heads in a single
      myosin molecule tend to interact with each other rather than with heads from
      adjacent molecules. Evidence has also been presented that the head tilt is away
      from the M-band. Here we seek to confirm these conclusions using a totally
      independent method. By using 3D helical reconstruction of isolated myosin
      filaments the known perturbation of the head array in vertebrate muscles was
      inevitably averaged out. The 3D reconstruction was therefore compared with the X
      ray model after it too had been helically averaged. The resulting images showed
      the same characteristic features: heads projecting out from the filament backbone
      to high radius and the motor domains at higher radius and further away from the M
      band than the light-chain-binding neck domains (lever arms) of the heads.

PMID- 12064943
TI  - Structure and nucleotide-dependent changes of thick filaments in relaxed and
      rigor plaice fin muscle.
AB  - The myosin crossbridge array, positions of non-crossbridge densities on the
      backbone, and the A-band "end filaments" have been compared in chemically
      skinned, unfixed, uncryoprotected relaxed, and rigor plaice fin muscles using the
      freeze-fracture, deep-etch, rotary-shadowing technique. The images provide a
      direct demonstration of the helical packing of the myosin heads in situ in
      relaxed muscle and show rearrangements of the myosin heads, and possibly of other
      myosin filament proteins, when the heads lose ATP on going into rigor. In the H
      zone these changes are consistent with crossbridge changes previously shown by
      others using freeze-substitution. In addition, new evidence is presented of
      protein rearrangements in the M-region (bare zone), associated with the
      transition from the relaxed to the rigor state, including a 27-nm increase in the
      apparent width of the M-region. This is interpreted as being mostly due to loss
      or rearrangement of a nonmyosin (M9) protein component at the M-region edge. The
      structure and titin periodicity of the end-filaments are described, as are
      suggestions of titin structure on the myosin filament backbone.

PMID- 12064944
TI  - Regulation of coiled-coil assembly in tropomyosins.
AB  - Tropomyosins (TMs) are a family of actin filament-binding proteins. They consist
      of nearly 100% alpha-helix and assemble into parallel coiled-coil dimers. In
      vertebrates, TMs are encoded by four genes that give rise to at least 17 distinct
      isoforms through the use of alternative RNA splicing and alternative promoters.
      We have studied various aspects of the coiled-coil interactions among muscle and
      nonmuscle isoforms by the use of transfection of epitope-tagged constructs,
      followed by immunoprecipitation, SDS-PAGE, and Western blot analyses. For coiled
      coil interactions between high-molecular-weight isoforms (284 amino acids), the
      information for homo- versus heterodimerization is contained in large part within
      the alternatively spliced exons of nonmuscle and muscle (skeletal and smooth)
      isoforms. Furthermore, sequences located in alternatively spliced exons encoding
      amino acids 39-80 (exons 2a/2b), amino acids 189-213 (exons 6a/6b), and amino
      acids 258-284 (exons 9a/9d) are critical for the selective formation of homo-
      versus heterodimers. Among low-molecular-weight isoforms (248 amino acids), TM-4
      and TM-5 can form either homodimers or heterodimers. The trigger sequence (amino
      acids 190-202) is required for homodimerization of TM-4, but not
      heterodimerization of TM-4 with TM-5. How the dimeric state of TMs might play a
      role in their cellular localization and function is discussed.

PMID- 12064945
TI  - Towards a complete atomic structure of spectrin family proteins.
AB  - The spectrin family of proteins represents a discrete group of cytoskeletal
      proteins comprising principally alpha-actinin, spectrin, dystrophin, and
      homologues and isoforms. They all share three main structural and functional
      motifs, namely, the spectrin repeat, EF-hands, and a CH domain-containing actin
      binding domain. These proteins are variously involved in organisation of the
      actin cytoskeleton, membrane cytoskeleton architecture, cell adhesion, and
      contractile apparatus. The highly modular nature of these molecules has been a
      hindrance to the determination of their complete structures due to the inherent
      flexibility imparted on the proteins, but has also been an asset, inasmuch as the
      individual modules were of a size amenable to structural analysis by both
      crystallographic and NMR approaches. Representative structures of all the major
      domains shared by spectrin family proteins have now been solved at atomic
      resolution, including in some cases multiple domains from several family members.
      High-resolution structures, coupled with lower resolution methods to determine
      the overall molecular shape of these proteins, allow us for the first time to
      build complete atomic structures of the spectrin family of proteins.

PMID- 12064946
TI  - PEVK domain of titin: an entropic spring with actin-binding properties.
AB  - The PEVK domain of the giant muscle protein titin is a proline-rich sequence with
      unknown secondary/tertiary structure. Here we compared the force-extension
      behavior of cloned cardiac PEVK titin measured by single-molecule atomic force
      spectroscopy with the extensibility of the PEVK domain measured in intact cardiac
      muscle sarcomeres. The analysis revealed that cardiac PEVK titin acts as an
      entropic spring with the properties of a random coil exhibiting mechanical
      conformations of different flexibility. Since in situ, titin is in close
      proximity to the thin filaments, we also studied whether the PEVK domain of
      cardiac or skeletal titin may interact with actin filaments. Interaction was
      indeed found in the in vitro motility assay, in which recombinant PEVK titin
      constructs slowed down the sliding velocity of actin filaments over myosin.
      Skeletal PEVK titin affected the actin sliding to a lesser degree than cardiac
      PEVK titin. The cardiac PEVK effect was partially suppressed by physiological
      Ca(2+) concentrations, whereas the skeletal PEVK effect was independent of
      [Ca(2+)]. Cosedimentation assays confirmed the Ca(2+)-modulated actin-binding
      propensity of cardiac PEVK titin, but did not detect interaction between actin
      and skeletal PEVK titin. In myofibrils, the relatively weak actin-PEVK
      interaction gives rise to a viscous force component opposing filament sliding.
      Thus, the PEVK domain contributes not only to the extensibility of the sarcomere,
      but also affects contractile properties.

PMID- 12064947
TI  - The role of unstructured highly charged regions on the stability and specificity
      of dimerization of two-stranded alpha-helical coiled-coils: analysis of the neck
      hinge region of the kinesin-like motor protein Kif3A.
AB  - We investigated the folding, stability, and specificity of dimerization of the
      neck-hinge region (residues 356-416) of the kinesin-like protein Kif3A. We showed
      that the predicted coiled-coil on its own (residues 356-377) will fold
      autonomously in solution. We then explored the ability of oppositely charged
      regions to specify heterodimer formation in coiled-coils by synthesizing analogs
      of the neck coiled-coil region with and without various negatively and positively
      charged extensions to the C-terminus of the neck coiled-coil and characterizing
      these analogs by circular dichroism spectroscopy. The charged region alone
      (residues 378-416) adopted a random-coil structure and this region remained
      unfolded in the presence of the coiled-coil. Redox experiments demonstrated that
      oppositely charged regions specified the formation of a hetero-two-stranded
      coiled-coil. Denaturation studies with urea demonstrated a decrease in coiled
      coil stability with the addition of negatively charged residues in the
      homostranded coiled-coil; conversely, the addition of the positively charged
      region (residues 403-416) of Kif3A C-terminally to the neck coiled-coil did not
      affect coiled-coil stability. Overall, our results suggest that electrostatic
      attractions drive the specificity of heterodimerization of the coiled-coil, not
      the removal of positive or negative charge-charge repulsions, while maintaining
      the stability of the heterodimer compared to that of the stablest homodimer.

PMID- 12064948
TI  - Helix capping interactions stabilize the N-terminus of the kinesin neck coiled
      coil.
AB  - In an effort to understand how specific structural features within the kinesin
      neck, a region of the heavy chain located between the catalytic core and stalk
      domains, may contribute to motor processivity (an ability to remain attached to
      the microtubule filament), we have prepared several synthetic peptides
      corresponding to the neck region of human conventional kinesin and determined
      their secondary structure content and stability by CD spectroscopy. Our results
      show that the coiled-coil dimerization domain within the human kinesin neck
      region corresponds to residues 337 to 369 in solution, and thus is in excellent
      agreement with the recent X-ray crystallographic structures of rat brain kinesin.
      Further, we show that the first and last heptads of this region are absolutely
      critical for creating the high stability and association of the dimeric
      structure. Interestingly, addition of the 7 N-terminal neck-linker residues (330
      336) to the coiled-coil domain significantly increased its stability (Delta
      GdnHCl midpoint of 1 M or an increase of approximately 1.5 kcal/mol), indicating
      that a strong structural link exists between the neck-linker and coiled-coil
      region. Subsequent high-resolution structural analysis of the residues located at
      the junction of the neck-linker and coiled-coil revealed the presence of the two
      helix capping motifs, the capping box (a reciprocal interaction of Thr 336 with
      Gln 339) and the hydrophobic staple (a hydrophobic packing interaction of Leu 335
      with Trp 340). Substitution of Leu 335 and Thr 336 (the capping residues) with
      Gly completely eliminated the increased stability of the coiled-coil region
      observed in the presence of the neck-linker residues. Correspondingly,
      substitution of Trp 340, the first hydrophobic core d position residue of the
      coiled-coil, with an Ala residue resulted in a greater than expected decrease in
      stability and helicity of the coiled-coil structure. Subsequent analysis of the X
      ray structure and substitution analysis of Lys 341 revealed that Trp 340 makes an
      important interchain hydrophobic interaction with Lys 341 of the opposite chain.
      Taken together these results reveal that a set of strong intra- and inter-chain
      interactions made up of the helix "capping box," "hydrophobic staple," and the
      newly identified "Leu-Trp-Lys sandwich" motifs stabilize the kinesin neck coiled
      coil structure, thus preventing it from fraying and unfolding.

PMID- 12064949
TI  - Review: conformation and folding of novel beta-structural elements in viral fiber
      proteins: the triple beta-spiral and triple beta-helix.
AB  - Apart from alpha-helical coiled coils and the collagen triple helices, fibrous
      proteins can contain beta-structure in various conformations. Elongated enzymes
      such as pectate lyase and the bacteriophage P22 tailspike protein contain single
      stranded beta-helices. Virus and bacteriophage fibers, which are often trimeric,
      have been shown to contain novel triple-stranded beta-structures such as the
      triple beta-spiral and the triple beta-helix. The conformation and folding of
      viral fibers containing beta-structure are discussed.

PMID- 12064951
TI  - A change in the make-up of medicine.

PMID- 12064950
TI  - Different molecular mechanics displayed by titin's constitutively and
      differentially expressed tandem Ig segments.
AB  - Titin is a giant elastic protein responsible for passive force generated by the
      stretched striated-muscle sarcomere. Passive force develops in titin's extensible
      region which consists of the PEVK segment in series with tandemly arranged
      immunoglobulin (Ig)-like domains. Here we studied the mechanics of tandem Ig
      segments from the differentially spliced (I65-70) and constitutive (I91-98)
      regions by using an atomic force microscope specialized for stretching single
      molecules. The mechanical stability of I65-70 domains was found to be different
      from that of I91-98 domains. In the range of stretch rates studied (0.05-1.00
      microm/s) lower average domain unfolding forces for I65-70 were associated with a
      weaker stretch-rate dependence of the unfolding force, suggesting that the
      differences in the mechanical stabilities of the segments derive from differences
      in the zero force unfolding rate (K(0)(u)) and the characteristic distance
      (location of the barrier) along the unfolding reaction coordinate (DeltaX(u)). No
      effect of calcium was found on unfolding forces and persistence length of
      unfolded domains. To explore the structural basis of the differences in
      mechanical stabilities of the two fragment types, we compared the amino acid
      sequence of I65-70 domains with that of I91-98 domains and by using homology
      modeling analyzed how sequence variations may affect folding free energies.
      Simulations suggest that differences in domain stability are unlikely to be
      caused by variation in the number of hydrogen bonds between the force-bearing
      beta-strands at the domain's N- and C-termini. Rather, they may be due to
      differences in hydrophobic contacts and strand orientations.

PMID- 12064952
TI  - Scatter irradiation in childhood causes thyroid cancer.

PMID- 12064953
TI  - Ambulatory blood pressure monitoring and white coat hypertension: saving costs.

PMID- 12064954
TI  - The control of meningococcal disease.

PMID- 12064955
TI  - Cosmetic surgery history and health service use in midlife: Women's Health
      Australia.
AB  - OBJECTIVE: To explore, among middle-aged women, the relationship between having
      ever had cosmetic surgery and the frequency of use of other health services.
      DESIGN: Retrospective analysis of cross-sectional survey data from the Women's
      Health Australia (WHA) study. SETTING AND PARTICIPANTS: A nationally
      representative sample of the "mid-aged" (45-50 years) cohort of women who
      participated in the 1996 WHA baseline postal survey. Responses were received from
      14 100 women (a response rate of 54%). RESULTS: Seven per cent of women reported
      ever having had cosmetic surgery. After adjusting for demographic variables,
      multivariate analysis confirmed that women who had had cosmetic surgery were
      significantly more likely to use health services more frequently (eg, surgical
      procedures, consultations with specialists and alternative healthcare providers).
      Cosmetic surgery was also associated with a greater number of chronic illnesses
      and use of medication for anxiety and sleep problems. CONCLUSION: Further
      research is needed to determine whether cosmetic surgery is directly related to
      health conditions or to attitudinal or psychosocial variables. Such research
      should examine whether alternative interventions may be more cost-effective in
      dealing with the issues that motivate women to seek cosmetic surgery.

PMID- 12064956
TI  - Cost analysis of ambulatory blood pressure monitoring in initiating
      antihypertensive drug treatment in Australian general practice.
AB  - OBJECTIVE: To compare the cost of ambulatory blood pressure monitoring (ABPM)
      with the putative savings made through treatment avoided by identification and
      non-treatment of those with "white coat" hypertension. DESIGN: A cost analysis
      based on a model of four alternative strategies (no ABPM, yearly, two-yearly, or
      three-yearly monitoring) over a seven-year period applied to a case series from
      Australian general practice. PARTICIPANTS: 62 patients newly diagnosed by their
      GPs as having hypertension and requiring drug treatment. MAIN OUTCOME MEASURES:
      The proportion of patients shown to not need treatment. The discounted costs to
      the Pharmaceutical Benefits Scheme, Medical Benefits Scheme and patients.
      RESULTS: 16 of 62 patients (26%; 95% CI, 15%-37%) were normotensive on ABPM and
      did not require treatment. All monitoring strategies are more expensive in the
      first year, but the initial costs are offset by year 3 and the monitoring
      strategies are cost saving thereafter. Sensitivity analysis shows that this
      result holds across a range of costs of pharmacotherapy and proportion of
      patients with white coat hypertension. CONCLUSION: The additional costs of 24
      hour ABPM in the first year are offset by savings associated with patients with
      white coat hypertension who would otherwise have been treated.

PMID- 12064957
TI  - Thyroid neoplasia following irradiation in adolescent and young adult survivors
      of childhood cancer.
AB  - OBJECTIVES: To describe a cohort of survivors of childhood malignancy at risk of
      developing thyroid abnormality, and propose guidelines for management of such
      patients. DESIGN: Retrospective case series. SETTING: Late-effects oncology
      clinic at a large children's hospital in Sydney. SUBJECTS: 142 patients who had
      received irradiation to the thyroid from the 1970s onwards, who attended the late
      effects clinic from May 1989 to December 1998. INTERVENTIONS: Thyroid palpation
      by an endocrinologist or surgeon, serum thyroid-stimulating hormone assay and
      thyroid ultrasound examination were performed on all subjects and, depending on
      findings, some subjects proceeded to fine-needle biopsy or surgery (total
      thyroidectomy). A few patients required adjuvant (131)I administration. OUTCOME
      MEASURES: Radiation dose received; results of thyroid palpation; thyroid function
      tests; ultrasound findings; diagnosis of the abnormalities; and outcomes of
      surgical interventions. RESULTS: 49 subjects (24 of 65 patients who received
      scatter irradiation to the thyroid and 25 of 78 patients who received direct
      irradiation) had thyroid surgery. Of these, 12 in the scatter and six in the
      direct irradiation group were found to have thyroid malignancy. Fifty subjects
      with abnormal ultrasound results remain under surveillance. Having a palpable
      thyroid was predictive of malignancy, but age at original diagnosis, sex, current
      age, time since irradiation, radiation dose, nodule type and nodal involvement
      were not. CONCLUSION: There is a significant risk of cancer in thyroid glands
      exposed to radiation as part of therapy for childhood cancer. This risk is
      greater for patients who received scatter (versus direct) irradiation. Nodular
      change is usually not apparent for many years, so lifelong surveillance is
      necessary. Palpation alone is not sufficient to detect thyroid cancer and thyroid
      ultrasound examination is recommended.

PMID- 12064958
TI  - Ambulatory blood pressure monitoring.
AB  - End-organ damage associated with hypertension is more closely related to
      ambulatory blood pressure (ABP) than clinic or casual blood pressure
      measurements. ABP measurements give better prediction of clinical outcome than
      clinic or casual blood pressure measurements. The technique of ABP monitoring
      (ABPM) is specialised; validated monitors and appropriate quality control
      measures should be used. Interpretation of ABP profile should include mean
      daytime, night-time (sleep) and 24-hour measurements, and consideration of diary
      information and time of drug treatment. Reports may also include ABP "loads"
      (percentage area under the blood pressure curve above set limits) for daytime and
      night-time periods. Normal blood pressure values for adults are < 135/85 mmHg for
      daytime, < 120/75 mmHg for night-time, and < 130/80 mmHg for 24 hours. ABPM is
      indicated to exclude "white coat" hypertension and has a role in assessing
      apparent drug-resistant hypertension, symptomatic hypotension or hypertension, in
      the elderly, in hypertension in pregnancy, and to assess adequacy of control in
      patients at high risk of cardiovascular disease. White coat hypertension requires
      continued surveillance; patients who display this phenomenon may, in time,
      develop established hypertension. Appropriate use of ABPM may result in cost
      savings. Randomised controlled trials comparing management based on clinic or
      casual versus ABP measurements are needed.

PMID- 12064959
TI  - Fulminant hepatic failure from herpes simplex in pregnancy.

PMID- 12064960
TI  - Using "anti-ageing" to market cosmetic surgery: just good business, or another
      wrinkle on the face of medical practice?
AB  - Potential consequences of the deregulation of advertising by doctors are examined
      using the example of practitioners who promote cosmetic procedures by exploiting
      body image concerns in a society that is both ageing and youth-oriented.

PMID- 12064961
TI  - Does cosmetic surgery improve psychosocial wellbeing?
AB  - Both men and women are becoming increasingly concerned about their physical
      appearance and are seeking cosmetic enhancement. Most studies report that people
      are generally happy with the outcome of cosmetic procedures, but little rigorous
      evaluation has been done. More extensive ("type change") procedures (eg,
      rhinoplasty) appear to require greater psychological adjustment by the patient
      than "restorative" procedures (eg, face-lift). Patients who have unrealistic
      expectations of outcome are more likely to be dissatisfied with cosmetic
      procedures. Some people are never satisfied with cosmetic interventions, despite
      good procedural outcomes. Some of these have a psychiatric disorder called "body
      dysmorphic disorder".

PMID- 12064962
TI  - Biological agents as weapons 2: anthrax and plague.
AB  - Although most naturally occurring infections with anthrax and plague are
      cutaneous, both organisms are most likely to be deliberately disseminated in
      aerosolised form, resulting in severe pulmonary illness. Mortality from both
      would be high and rapid in the absence of early and effective treatment, making
      swift and effective liaison between alert clinicians and public health
      authorities crucial to an effective response. Differentiating features include
      mediastinal widening (anthrax) and haemoptysis (plague). Doxycycline and
      ciprofloxacin are effective agents for prophylaxis and treatment for both
      diseases. Medical advocacy for strengthening the Biological Weapons Convention,
      particularly with an enforceable protocol including verification and compliance
      provisions, is needed.

PMID- 12064963
TI  - 7: Soft tissue, bone and joint infections.
AB  - Soft tissue infections are common and usually respond rapidly to oral
      antibiotics; if empirical therapy fails then exposure to unusual organisms should
      be considered. Septic arthritis requires early recognition, identification of the
      infecting pathogen and urgent joint washout to prevent irreversible cartilage and
      bone destruction. Prosthetic joint infection is uncommon but has high morbidity;
      the best outcomes are achieved with removal of the prosthesis and replacement
      after at least six weeks of antibiotic therapy. Osteomyelitis often complicates
      diabetic foot infection with ulceration and is rarely cured by antibiotics alone;
      early surgical intervention achieves the best outcome.

PMID- 12064964
TI  - Thrombophilia screening and adverse pregnancy outcomes associated with
      uteroplacental insufficiency.

PMID- 12064965
TI  - Safety of hormone replacement therapy after mastectomy.

PMID- 12064966
TI  - Genotype-phenotype correlations with personality traits of healthcare
      professionals: a new use for the Human Genome Project.

PMID- 12064967
TI  - Essential role of fats throughout the lifecycle: summary and recommendations.

PMID- 12064968
TI  - Essential role of fats throughout the lifecycle. Background: the renaissance of
      fat: roles in membrane structure, signal transduction and gene expression.
AB  - The intracellular and intramembrane profiles of fatty acids mirror those of
      dietary fat intake. The properties of transporter and receptor proteins embedded
      within cell membranes are influenced by the composition of the phospholipid
      membrane of cells. Many cell-signalling pathways involve lipids or lipid-derived
      molecules. Specific fatty acids are increasingly being identified as key
      regulators of gene expression and tissue differentiation.

PMID- 12064969
TI  - The role of fats in the lifecycle stages: pregnancy and the first year of life.
AB  - Fish oil supplementation during pregnancy has been tested in several trials, with
      small positive effects on length of gestation; there have been no beneficial or
      harmful effects on cognitive development or growth of infants as a result of fish
      oil supplementation in pregnancy. The strongest evidence for good developmental
      outcomes for infants supports breastfeeding for at least six months. Preterm
      infants are at the greatest risk of DHA deficiency and there is strong evidence
      for the positive effects of DHA on visual and cognitive outcomes that has
      resulted in all Australian preterm formulas being supplemented with DHA. Debate
      continues about the importance of DHA supplementation for term infants; the
      current consensus is that the benefits of DHA supplementation in term infants are
      smaller than for preterm infants.

PMID- 12064970
TI  - The role of fats in the lifecycle stages: toddlers to preschool.
AB  - Toddlers (1-2-year-olds) are in transition from the high-fat diet of infancy to
      the relatively low-fat diet of preschoolers, school-aged children and
      adolescents. Toddlers and preschoolers need to be continually encouraged to try a
      wide a range of foods supplying all types of fats, and with the emphasis on
      nutrient-dense foods. Reduced-fat and skim milks are not appropriate for
      toddlers, because milk is a major fat source for 1-2-year-olds, but reduced-fat
      milks are encouraged for preschool-aged children. No solid evidence exists to
      support the manipulation of dietary fat for the treatment of attention deficit
      hyperactivity disorder or the prevention and treatment of asthma.

PMID- 12064971
TI  - The role of fats in the lifecycle stages: the primary school years.
AB  - The most significant influence on a child's eating patterns is family eating
      behaviour, specifically in encouraging fruit and vegetable intake. The
      recommended 30% total energy from fat can be achieved by practical changes in
      eating pattern, such as limiting high fat snack foods to occasional or treat
      items. Saturated fat intake can be reduced to recommended levels by reducing
      intake from whole milk and yoghurt, ice-cream, and potato and snack items, and
      replacing part of this with monounsaturated and polyunsaturated fatty acid
      sources such as nuts, seeds, margarine or hummus dips.

PMID- 12064972
TI  - The role of fats in the lifecycle stages: adolescence and young adulthood.
AB  - Advice supporting regular physical activity, healthy food choices and smoking
      avoidance is definitely warranted in adolescents, particularly where early
      negative eating trends are evident. A difference in emphasis may be required for
      males and females with respect to physical activity and diet. The amount of
      dietary fat is important in maintaining energy balance, and the type of fat is
      important in reducing the development of heart disease. Low-fat foods are
      suitable at this lifestage, but it is also important to avoid sources of "hidden"
      saturated fatty acids (biscuits and fast foods) and to include sources of
      polyunsaturated and monounsaturated fatty acids (oils, margarine, lean meat,
      poultry and nuts).

PMID- 12064973
TI  - The role of fats in the lifecycle stages. Adulthood--prevention: cardiovascular
      disease.
AB  - Coronary heart disease (CHD) risk is positively linked with dietary saturates and
      negatively linked with polyunsaturated fatty acids (PUFAs). Consumption of omega
      3 fatty acids, such as in fish, appears highly protective against CHD. PUFAs
      (linoleic acid or omega-6) lower low-density lipoprotein (LDL) cholesterol levels
      most, and saturates, especially butter fat, raise LDL levels most. Fish oil fatty
      acids (omega-3) lower triglyceride and raise high-density lipoprotein (HDL)
      cholesterol levels. A higher ratio of dietary omega-3 to omega-6 fatty acids than
      is currently consumed in our population may be desirable, and can be achieved by
      increasing consumption of fish and alpha-linolenic acid in canola, soy and
      flaxseed oils. Large prospective trials show that people who experience least CHD
      have a pattern of eating that is rich in fish, PUFAs, whole-grain cereals, fruits
      and vegetables and low-fat dairy foods, and low in saturates from dairy fat, meat
      fat and fried foods.

PMID- 12064974
TI  - The role of fats in the lifecycle stages. Adulthood--prevention: rheumatoid
      arthritis.
AB  - There is evidence for preventive and therapeutic effects of dietary omega-3 fats
      in rheumatoid arthritis. While doses of up to several grams per day of fish
      derived fatty acids may be necessary for therapeutic effects in long-standing
      rheumatoid arthritis, much lower doses should provide benefits to reduce the
      mortality from cardiovascular disease in this inflammatory disorder.

PMID- 12064975
TI  - The role of fats in the lifecycle stages. Adulthood--prevention: diabetes.
AB  - Total fat intake is not related to the risk of diabetes, but, while
      polyunsaturated fat reduces the risk, monounsaturated fat is neutral and
      saturated fat may increase the risk. Body weight is far more critical than
      macronutrient composition.

PMID- 12064976
TI  - The role of fats in the lifecycle stages. Adulthood--treatment: cholesterol
      lowering with plant sterols.
AB  - Margarines enriched with plant sterols are effective at lowering low-density
      lipoprotein (LDL) cholesterol levels when eaten as recommended. LDL-cholesterol
      level reductions of more than 10% are achieved in most people. Phytosterol
      containing foods are valuable additions to other cholesterol-lowering treatments,
      including statins. They should be considered for all patients with increased
      cardiovascular risk factors in whom LDL reduction is desirable. The only
      recognised possible adverse effect is reduction in some carotenoids in plasma,
      but this can be overcome by eating an additional serving of a carotenoid-rich
      (yellow or orange) fruit or vegetable.

PMID- 12064977
TI  - The role of fats in the lifecycle stages. Dietary implications: advising patients
      about fat in the diet.

PMID- 12064978
TI  - Antibiotic guidelines: improved implementation is the challenge.

PMID- 12064979
TI  - Kidney disease: are you at risk?

PMID- 12064980
TI  - Bushfires, air pollution and asthma.

PMID- 12064981
TI  - Fire ants in Australia: a new medical and ecological hazard.

PMID- 12064982
TI  - Anaphylaxis due to Red Imported Fire Ant sting.
AB  - The invasive Red Imported Fire Ant (Solenopsis invicta Buren) is well established
      at two locations in the Brisbane area, and we report a patient with anaphylaxis
      after a sting. The potential for anaphylactic events in Australia due to S.
      invicta will be greater than for native ants because of its unusual venom, its
      habit of forming supercolonies in grassy areas, and its aggressive group
      territorial defence, which can result in multiple stings.

PMID- 12064983
TI  - Ceftriaxone and cefotaxime use in Victorian hospitals.
AB  - OBJECTIVE: To determine patterns of use of ceftriaxone and cefotaxime (CEFX) in
      Victorian hospitals and to identify areas for improvement. DESIGN, PATIENTS AND
      SETTING: A concurrent, observational evaluation of CEFX use in patients
      commencing a course of these drugs between 8 and 14 September, 1999, in 51
      Victorian hospitals. MAIN OUTCOME MEASURES: Proportion of patients treated with
      CEFX; indications; duration of use; concordance with recommendations of national
      antibiotic guidelines (Therapeutic guidelines: antibiotic, 10th edition [AG10]).
      RESULTS: 671 patients were treated with CEFX. The overall rate of use was 43
      patients per 1000 inpatient separations. Treatment of respiratory tract infection
      accounted for 352 patients (52%) and surgical prophylaxis for 99 patients (15%).
      Treatment of skin/soft tissue, urinary tract and gastrointestinal tract
      infections accounted for about 7% of patients each. The median duration of CEFX
      courses was 3.0 days. The overall rate of concordance with indications
      recommended in AG10 was 27%. The rate of concordance for empirical treatment of
      respiratory tract infection was 24%. Of the 195 patients treated empirically with
      CEFX for community-acquired respiratory tract infection and assessed as non
      concordant, 64% did not have radiological evidence of pneumonia, and a further
      30% did not fulfill the criteria for severe pneumonia. All courses given for
      surgical prophylaxis were non-concordant. CONCLUSIONS: CEFX is widely used in
      Victorian hospitals, mostly to treat lower respiratory tract infection and in
      surgical prophylaxis of infection. The rate of concordance with AG10 is low.
      Potential areas for intervention include empirical treatment of respiratory tract
      infection and use in surgical prophylaxis.

PMID- 12064984
TI  - Naltrexone in alcohol dependence: a randomised controlled trial of effectiveness
      in a standard clinical setting.
AB  - OBJECTIVES: To determine whether naltrexone is beneficial in the treatment of
      alcohol dependence in the absence of obligatory psychosocial intervention.
      DESIGN: Multicentre, randomised, double-blind, placebo-controlled trial. SETTING:
      Hospital-based drug and alcohol clinics, 18 March 1998 - 22 October 1999.
      PATIENTS: 107 patients (mean age, 45 years) fulfilling Diagnostic and statistical
      manual of mental disorders (4th edition) criteria for alcohol dependence.
      INTERVENTIONS: Patients with alcohol dependence were randomly allocated to
      naltrexone (50 mg/day) or placebo for 12 weeks. They were medically assessed,
      reviewed and advised by one physician, and encouraged to strive for abstinence
      and attend counselling and/or Alcoholics Anonymous, but this was not obligatory.
      MAIN OUTCOME MEASURES: Relapse rate; time to first relapse; side effects.
      RESULTS: On an intention-to-treat basis, the Kaplan-Meier survival curve showed a
      clear advantage in relapse rates for naltrexone over placebo (log-rank test,
      chi(2)(1) = 4.15; P = 0.042). This treatment effect was most marked in the first
      6 weeks of the trial. The median time to relapse was 90 days for naltrexone,
      compared with 42 days for placebo. In absolute numbers, 19 of 56 patients (33.9%)
      taking naltrexone relapsed, compared with 27 of 51 patients (52.9%) taking
      placebo (P = 0.047). Naltrexone was well tolerated. CONCLUSIONS: Unlike previous
      studies, we have shown that naltrexone with adjunctive medical advice is
      effective in the treatment of alcohol dependence irrespective of whether it is
      accompanied by psychosocial interventions.

PMID- 12064985
TI  - Exposure to bushfire smoke and asthma: an ecological study.
AB  - OBJECTIVE: To examine the relationship between the mean daily concentration of
      respirable particles arising from bushfire smoke and hospital presentations for
      asthma. DESIGN AND SETTING: An ecological study conducted in Darwin (Northern
      Territory, Australia) from 1 April - 31 October 2000, a period characterised by
      minimal rainfall and almost continuous bushfire activity in the proximate
      bushland. The exposure variable was the mean atmospheric concentration of
      particles of 10 microns or less in aerodynamic diameter (PM(10)) per cubic metre
      per 24-hour period. OUTCOME MEASURE: The daily number of presentations for asthma
      to the Emergency Department of Royal Darwin Hospital. RESULTS: There was a
      significant increase in asthma presentations with each 10-microg/m(3) increase in
      PM(10) concentration, even after adjusting for weekly rates of influenza and for
      weekend or weekday (adjusted rate ratio, 1.20; 95% CI, 1.09-1.34; P < 0.001). The
      strongest effect was seen on days when the PM(10) was above 40 microg/m(3)
      (adjusted rate ratio, 2.39; 95% CI, 1.46-3.90), compared with days when PM(10)
      levels were less than 10 microg/m(3). CONCLUSION: Airborne particulates from
      bushfires should be considered as injurious to human health as those from other
      sources. Thus, the control of smoke pollution from bushfires in urban areas
      presents an additional challenge for managers of fireprone landscapes.

PMID- 12064986
TI  - Primary care budget holding in the United Kingdom National Health Service:
      learning from a decade of health service reform.
AB  - 1. The United Kingdom National Health Service (NHS) has experienced 10 years of
      primary care budget holding in a variety of forms. 2. Half of all general
      practitioners had joined the GP fundholding scheme by 1997, and many others had
      joined broader GP commissioning groups, but fundholders controlled only about 20%
      of the budget for hospital and community health services. 3. Research on
      fundholding and commissioning groups suggests that delegation of budgets produced
      some gains in the range and effectiveness of services, but also had significant
      management costs and inequities. 4. From 1999, all primary care professionals
      joined Primary Care Groups, which are now becoming Primary Care Trusts (PCTs).
      PCTs will control three-quarters of the healthcare budget and provide all primary
      and community services as well as commissioning hospital care. 5. Control of a
      unified healthcare budget presents opportunities to improve quality, increase
      integration of services, reduce inequities and improve health. However, PCTs are
      threatened by a growing gap between capacity and expectations, and by continuing
      tension between devolution of power and increasingly prescriptive management by
      central government.

PMID- 12064987
TI  - Collaborating with industry: choices for Australian medicine and universities.
AB  - 1. Collaboration between industry and academia is becoming increasingly prevalent
      and successful in Australia. 2. To encourage and foster these relationships while
      preventing excesses, Australia needs to act now to create ethical, legal and
      legislative frameworks for collaboration. 3. As the United States has progressed
      further than Australia in fostering and controlling collaboration between
      industry and academia, Australia has the opportunity to learn from the US
      experience. 4. To speed the pace of development, Australia needs to consider
      making changes to legislation and increasing the level of government funding,
      either directly or by the creation of incentives for investment of venture
      capital and superannuation funds in biotechnology.

PMID- 12064988
TI  - Cervical screening: time to change the policy.
AB  - 1. In 1991, the "organised approach to preventing cancer of the cervix"
      recommended Pap smears every two years for women aged 18-70 years who have ever
      been sexually active. 2. The two-year interval was a compromise step towards the
      scientifically supported three-year interval, as many influential groups were
      strongly attached to annual screening. When other components of the organised
      approach were in place, the policy was to be reviewed. 3. Since the safeguards in
      the "organised approach" have been proven effective, it is appropriate to change
      the policy to recommend a three-year interval. Increasing the interval would
      allow more resources to be allocated to enrolling women currently underscreened
      and to evaluating and improving the program. 4. The age of commencing smears
      could also be reconsidered to reflect the balance of potential benefits and harm
      in young women, for whom cancer is very rare but follow-up investigation common.
      5. If consensus is not reached within the profession, an evidence-based decision
      may need to be made at the political level.

PMID- 12064989
TI  - Infectious diseases. 6: Sexually transmitted infections: new diagnostic
      approaches and treatments.
AB  - 1. Commercially available nucleic acid amplification assays (eg, polymerase or
      ligase chain reaction) are now the "gold standard" tests for genital chlamydial
      infection and also have a role in screening for gonococcal infection. 2. Single
      dose oral antibiotics are available for treatment of Chlamydia trachomatis,
      Neisseria gonorrhoeae and Trichomonas vaginalis infections. 3. Strains of N.
      gonorrhoeae in urban Australia are often penicillin resistant, while strains from
      South East Asia and those in homosexually active men may show high-level
      resistance to quinolones. 4. Imiquimod, a novel immune-response modifier, is now
      available for effective, safe, self-administered treatment of genital warts. 5.
      The Pap smear remains the cornerstone of screening for precursor lesions of
      cervical cancer, but human papillomavirus genotyping may have a role in clinical
      decision-making for women with equivocal or early precancerous lesions. 6.
      Treatment of primary genital herpes changes the clinical course, and long-term
      suppressive therapy is effective for those with multiple recurrences. New
      technologies have made diagnosis and screening easier for patients and clinicians

PMID- 12064990
TI  - Vitamin D deficiency is common in frail institutionalised older people in
      northern Sydney.

PMID- 12064991
TI  - Perhexiline toxicity related to citalopram use.

PMID- 12064992
TI  - Cholestasis associated with the use of pravastatin sodium.

PMID- 12064993
TI  - Paracetamol recall: a natural experiment influencing analgesic poisoning.

PMID- 12064994
TI  - Treatment failure due to methicillin-resistant Staphylococcus aureus (MRSA) with
      reduced susceptibility to vancomycin.

PMID- 12064995
TI  - Haemochromatosis: Red Cross Blood Service policy.

PMID- 12064996
TI  - An ecological perspective of cholesterol.

PMID- 12064997
TI  - Responding to the Australian experience of depression: the view of the Mental
      Health Council of Australia.

PMID- 12064998
TI  - General practitioners play a vital role in providing information.

PMID- 12064999
TI  - Responding to the Australian experience of depression. Promotion of the direct
      voice of consumers is critical for reducing stigma.

PMID- 12065000
TI  - Monitoring awareness of and attitudes to depression in Australia.
AB  - OBJECTIVES: To determine the degree of recognition and understanding of
      depression and its treatments in Australia in 2001, and detail factors and
      personal experiences that influence awareness of and attitudes to depression.
      DESIGN AND SETTING: Cross-sectional survey of a representative community sample
      (900 randomly selected respondents), via telephone interview, conducted 5-7
      October 2001. MAIN OUTCOME MEASURES: Reports of community awareness, knowledge
      and attitudes to depression and its treatments in Australia. RESULTS: The
      Australian community does not view mental health as a major general health issue.
      When asked specifically, depression was recognised as the most common mental
      health problem. Recognition of depression was greater among women and younger
      people. Most people (58%; 508/879) reported that they or a family member had
      experienced depression. People younger than 55 years and people with personal or
      family experiences of depression viewed depression as more disabling than other
      chronic medical conditions. Half the respondents differentiated depression from
      normal sadness. Awareness of common risk versus protective factors was limited.
      Most people endorsed a preference for self-help and non-pharmacological
      treatments, but community views of antidepressant drugs were less negative than
      expected. General practitioners were identified as the preferred point of first
      contact among healthcare professionals. CONCLUSIONS: Although mental health is
      still not highlighted as a major health issue, Australians do recognise
      depression as the major mental health problem. Women and younger people have more
      substantial knowledge about key aspects of depression and its treatments.

PMID- 12065001
TI  - Exploring the perspectives of people whose lives have been affected by
      depression.
AB  - OBJECTIVES: To describe the experiences of people whose lives have been affected
      by depression. DESIGN, SETTING AND PARTICIPANTS: Thematic review of data
      collected from 21 community meetings (1529 people, providing 911 evaluation
      forms) and nine focus groups (69 individuals) held nationally, and written
      feedback and website-based interactions with beyondblue: the national depression
      initiative between April and December 2001. MAIN OUTCOME MEASURES: Barriers to
      social participation experienced by people whose lives have been affected by
      depression, and their interactions with the healthcare system. RESULTS: The key
      theme was the experience of stigma, which was evident in healthcare settings and
      in barriers to social participation, particularly regarding employment.
      Inadequacies of primary care and specialist treatment systems were highlighted.
      Particular emphasis was placed on limited access to high-quality primary care and
      non-pharmacological care. The stigmatising attitudes of many healthcare providers
      were notable. Within society, lack of access to knowledge and self-care or mutual
      support services was evident. Lack of support both from and for people in caring
      roles was also emphasised. CONCLUSIONS: People with depression are subject to
      many of the same attitudes, inadequate healthcare and social barriers reported by
      people with psychotic disorders. Consumers and carers prioritise certain notions
      of illness, recovery and quality of healthcare, and expect healthcare providers
      to respond to these concerns.

PMID- 12065002
TI  - Treating depression: the beyondblue guidelines for treating depression in primary
      care. "Not so much what you do but that you keep doing it".
AB  - 1. Most people with depression will be treated in general practice, either by the
      GP alone, or (for more serious depression) in partnership with specialist mental
      health services. 2. Treatment plans should always be based on thorough
      assessment, including the type, severity and duration of the depressive episode,
      and any stressors that contributed to the episode. 3. For mild and moderate
      depression, meta-analysis shows there is little difference in relative
      effectiveness of treatments, and continuation of therapy is more important than
      initial treatment choice. 4. The best outcomes are likely when a good therapeutic
      alliance is formed between a healthcare professional and the patient, and
      adequate treatment is provided over a long enough period. For pharmacological
      interventions, treatment should continue for: at least one year for a first
      episode of depression, and at least two years for repeated episodes or where
      there are other risk factors for relapse.

PMID- 12065003
TI  - Effectiveness of complementary and self-help treatments for depression.
AB  - OBJECTIVES: To review the evidence for the effectiveness of complementary and
      self-help treatments for depression. DATA SOURCES: Systematic literature search
      using PubMed, PsycLit, the Cochrane Library and previous review papers. DATA
      SYNTHESIS: Thirty-seven treatments were identified and grouped under the
      categories of medicines, physical treatments, lifestyle, and dietary changes. We
      give a description of each treatment, the rationale behind the treatment, a
      review of studies on effectiveness, and the level of evidence for the
      effectiveness studies. RESULTS: The treatments with the best evidence of
      effectiveness are St John's wort, exercise, bibliotherapy involving cognitive
      behaviour therapy and light therapy (for winter depression). There is some
      limited evidence to support the effectiveness of acupuncture, light therapy (for
      non-seasonal depression), massage therapy, negative air ionisation (for winter
      depression), relaxation therapy, S-adenosylmethionine, folate and yoga breathing
      exercises. CONCLUSION: Although none of the treatments reviewed is as well
      supported by evidence as standard treatments such as antidepressants and
      cognitive behaviour therapy, many warrant further research.

PMID- 12065005
TI  - Parasite elimination programs: at home and away.
AB  - A more coordinated, national approach to parasite control would have substantial
      benefits.

PMID- 12065004
TI  - The quality and accessibility of Australian depression sites on the World Wide
      Web.
AB  - OBJECTIVES: To provide information about Australian depression sites and the
      quality of their content; to identify possible indicators of the quality of site
      content; and determine the accessibility of Australian depression web sites.
      DESIGN: Cross-sectional survey of 15 Australian depression web sites. MAIN
      OUTCOME MEASURES: (i) Quality of treatment content (concordance of site
      information with evidence-based guidelines, number of evidence-based treatments
      recommended, discussion of other relevant issues, subjective rating of treatment
      content); (ii) potential quality indicators (conformity with DISCERN criteria,
      citation of scientific evidence); (iii) accessibility (search engine rank).
      RESULTS: Mean content quality scores were not high and site accessibility was
      poor. There was a consistent association between the quality-of-content measures
      and the DISCERN and scientific accountability scores. Search engine rank was not
      associated with content quality. CONCLUSIONS: The quality of information about
      depression on Australian websites could be improved. DISCERN may be a useful
      indicator of website quality, as may scientific accountability. The sites that
      received the highest quality-of-content ratings were beyondblue, BluePages,
      CRUfAD and InfraPsych.

PMID- 12065006
TI  - Rural health: why it matters.
AB  - Australia needs a distinctive "rural health" approach that recognises the
      valuable role played by the "outback" in our economy and our national psyche.

PMID- 12065007
TI  - Child sexual abuse revisited.
AB  - Notification of abuse should trigger initiatives to prevent further abuse and
      ameliorate adverse consequences.

PMID- 12065008
TI  - End-stage renal disease in the Northern Territory: current and future treatment
      costs.
AB  - OBJECTIVE: To compare hospital costs of Aboriginal and non-Aboriginal patients
      having haemodialysis treatment and forecast the future treatment cost. METHODS:
      The costs of patients with HD in the "Top End" of Australia's Northern Territory
      were estimated for the financial years 1996/97 and 1997/98 using a hospital
      costing model. We used an Autoregression Integrated Moving Average model to
      predict future demand. RESULTS: 165 patients (101 Aboriginal and 64 non
      Aboriginal) were treated at a total cost of $12.4 million in this two-year
      period. These 165 patients represented 0.7% of inpatients, 8.8% of total
      inpatient costs and 31.6% of total inpatient episodes of care in the Top End
      region. $9.5 million (77%) was spent on routine haemodialysis treatment and $2.9m
      (23%) on other hospitalisations. The average cost per routine haemodialysis
      treatment over the two-year period was $527, or $78 600 per patient treatment
      year. Hospitalisations for comorbidities occurred in 86% of Aboriginal and 39% of
      non-Aboriginal patients. Average cost per patient, number of admissions and
      length of hospital stays were all significantly greater for Aboriginals. We
      predict an average increase in the number of treatments of 12% each year over the
      next five years and a five-year cost of $49.8m. CONCLUSIONS: A multipronged
      strategy designed to reduce the prevalence and costs of renal failure is
      required.

PMID- 12065009
TI  - Sharing the true stories: improving communication between Aboriginal patients and
      healthcare workers.
AB  - OBJECTIVES: To identify factors limiting the effectiveness of communication
      between Aboriginal patients with end-stage renal disease and healthcare workers,
      and to identify strategies for improving communication. DESIGN: Qualitative
      study, gathering data through (a) videotaped interactions between patients and
      staff, and (b) in-depth interviews with all participants, in their first
      language, about their perceptions of the interaction, their interpretation of the
      video record and their broader experience with intercultural communication.
      SETTING: A satellite dialysis unit in suburban Darwin, Northern Territory. The
      interactions occurred between March and July 2001. PARTICIPANTS: Aboriginal
      patients from the Yolngu language group of north-east Arnhem Land and their
      medical, nursing and allied professional carers. MAIN OUTCOME MEASURES: Factors
      influencing the quality of communication. RESULTS: A shared understanding of key
      concepts was rarely achieved. Miscommunication often went unrecognised. Sources
      of miscommunication included lack of patient control over the language, timing,
      content and circumstances of interactions; differing modes of discourse;
      dominance of biomedical knowledge and marginalisation of Yolngu knowledge;
      absence of opportunities and resources to construct a body of shared
      understanding; cultural and linguistic distance; lack of staff training in
      intercultural communication; and lack of involvement of trained interpreters.
      CONCLUSIONS: Miscommunication is pervasive. Trained interpreters provide only a
      partial solution. Fundamental change is required for Aboriginal patients to have
      significant input into the management of their illness. Educational resources are
      needed to facilitate a shared understanding, not only of renal physiology,
      disease and treatment, but also of the cultural, social and economic dimensions
      of the illness experience of Aboriginal people.

PMID- 12065010
TI  - Workforce retention in rural and remote Australia: determining the factors that
      influence length of practice.
AB  - OBJECTIVES: To ascertain which factors are most significant in a general
      practitioner's decision to stay in rural practice and whether these retention
      factors vary in importance according to the geographical location of the practice
      and GP characteristics. DESIGN: National questionnaire survey. The method of
      paired comparisons was used to describe the relative importance of the retention
      items. SETTING: Non-metropolitan Australia, September 2001. PARTICIPANTS: A
      stratified sample of all rural GPs practising during April-June 2001. MAIN
      OUTCOME MEASURES: A rank ordering of factors influencing how long GPs stay in
      rural practice, and an index of their relative perceived importance. RESULTS:
      Professional considerations -- overwhelmingly, on-call arrangements -- are the
      most important factors determining GP retention in rural and remote areas. Rural
      doctors consistently ranked on-call arrangements, professional support and
      variety of rural practice as the top three issues, followed by local availability
      of services and geographical attractiveness. Proximity to a city or large
      regional centre was the least important factor. Retention factors varied
      according to geographical location and GPs' age, sex, family status, length of
      time in the practice, and hospital duties. CONCLUSIONS: A broad, integrated rural
      retention strategy is required to address on-call arrangements, provide
      professional support and ensure adequate time off for continuing medical
      education and recreation.

PMID- 12065011
TI  - Dispelling the myths about rural consultant physician practice: the Victorian
      Physicians Survey.
AB  - OBJECTIVE: To quantify the barriers to practising as a rural consultant
      physician. DESIGN: Cross-sectional postal survey. PARTICIPANTS: All 981
      practising consultant physicians in Victoria, Australia, who were Fellows of the
      Royal Australasian College of Physicians in 1999; 52 (100%) of rural physicians
      and 634 (68.2%) of metropolitan physicians completed the survey. MAIN OUTCOME
      MEASURES: Demographic and practice characteristics; barriers to rural practice.
      RESULTS: There were no rural female consultant physicians, and 35 of the 52 rural
      consultant physicians (67.3%) were born in a rural area. The most important
      perceived barriers to rural practice identified by both metropolitan and rural
      physicians were children's schooling (72.2%), spouse's occupation (65.7%), other
      issues related to children (66.7%) and difficulties getting back into
      metropolitan practice (45.7%). Among metropolitan physicians, barriers to rural
      practice differed by age, sex, place of birth and nationality. Returning to
      metropolitan practice, children and concern over procedures were more likely to
      be reported as barriers to rural practice among those aged 40 years or under, 41
      50 years and 51 years and over, respectively. CONCLUSION: The major barriers to
      rural practice identified by physicians lie outside the health sector, and
      particularly concern a perceived need for wider opportunities in children's
      education and spouse employment.

PMID- 12065012
TI  - Development of guidelines for non-indigenous people undertaking research among
      the indigenous population of north-east Victoria.
AB  - The Department of Rural Health, University of Melbourne, has developed a
      framework for conducting research in partnership with Indigenous communities. The
      framework addresses past inappropriate research practices, incorporates cultural
      understandings, and outlines culturally appropriate protocols. The four parts of
      the framework are a committee to initiate, direct and oversee all research
      projects; a Koorie Team to guide research; a set of research guidelines; and a
      policy for the department. The framework has been used to develop strong
      relations with Koorie communities and conduct various health projects.

PMID- 12065014
TI  - Specifying objectives and outcomes for clinical trials.

PMID- 12065013
TI  - The pharmacotherapy of smoking cessation.
AB  - 1. The great majority of smokers are chronically dependent on tobacco. This
      dependence arises from the rituals and sensory associations of smoking that are
      reinforced, within seconds, by a rapid burst of nicotine from the cigarette. 2.
      All forms of nicotine replacement therapy (NRT) -- gum, patches and inhaler --
      and bupropion are safe and effective for increasing smoking cessation rates in
      the short and long terms. 3. Other than those who are minimally dependent, all
      patients willing to quit should be offered one of these therapies unless
      contraindications exist. The effectiveness of drug treatments is multiplied when
      associated with effective counselling or behavioural treatments. 4. While NRT is
      not recommended during pregnancy or in patients with cardiac disease, if the
      alternative is smoking NRT is almost certainly safe. 5. Combination NRT (more
      than one therapy) may be indicated in patients who have failed monotherapy in
      association with withdrawal symptoms. 6. There are some specific
      contraindications to the use of bupropion. Its subsidised availability should not
      influence prescribers to ignore these.

PMID- 12065015
TI  - Which substitution pharmacotherapy is most effective in treating opioid
      dependence?

PMID- 12065016
TI  - Is subcutaneous or intramuscular naloxone as effective as intravenous naloxone in
      the treatment of life-threatening heroin overdose?

PMID- 12065017
TI  - Death and paramethoxyamphetamine -- an evolving problem.

PMID- 12065018
TI  - Relapsing vivax malaria.

PMID- 12065019
TI  - Household infrastructure in Aboriginal communities and the implications for
      health improvement.

PMID- 12065020
TI  - Diagnostic and therapeutic procedures among Australian hospital patients
      identified as indigenous.

PMID- 12065021
TI  - Hindsight bias in medicolegal expert reports.

PMID- 12065022
TI  - Predictive genetic testing in children.

PMID- 12065023
TI  - Ethics and evidence-based medicine.

PMID- 12065024
TI  - Aboriginal language interpreting service.

PMID- 12065025
TI  - Complete genome sequence of a novel extrachromosomal virus-like element
      identified in planarian Girardia tigrina.
AB  - BACKGROUND: Freshwater planarians are widely used as models for investigation of
      pattern formation and studies on genetic variation in populations. Despite
      extensive information on the biology and genetics of planaria, the occurrence and
      distribution of viruses in these animals remains an unexplored area of research.
      RESULTS: Using a combination of Suppression Subtractive Hybridization (SSH) and
      Mirror Orientation Selection (MOS), we compared the genomes of two strains of
      freshwater planarian, Girardia tigrina. The novel extrachromosomal DNA-containing
      virus-like element denoted PEVE (Planarian Extrachromosomal Virus-like Element)
      was identified in one planarian strain. The PEVE genome (about 7.5 kb) consists
      of two unique regions (Ul and Us) flanked by inverted repeats. Sequence analyses
      reveal that PEVE comprises two helicase-like sequences in the genome, of which
      the first is a homolog of a circoviral replication initiator protein (Rep), and
      the second is similar to the papillomavirus E1 helicase domain. PEVE genome
      exists in at least two variant forms with different arrangements of single
      stranded and double-stranded DNA stretches that correspond to the Us and Ul
      regions. Using PCR analysis and whole-mount in situ hybridization, we
      characterized PEVE distribution and expression in the planarian body.
      CONCLUSIONS: PEVE is the first viral element identified in free-living flatworms.
      This element differs from all known viruses and viral elements, and comprises two
      potential helicases that are homologous to proteins from distant viral phyla.
      PEVE is unevenly distributed in the worm body, and is detected in specific
      parenchyma cells.

PMID- 12065027
TI  - Infant gaze, head, face and self-touch at 4 months differentiate secure vs.
      avoidant attachment at 1 year: a microanalytic approach.
AB  - The study attempted to distinguish avoidant vs. secure infants at 1 year from 4
      month infant behavior only, during a face-to-face play interaction with the
      mother. Thirty-five 4-month-old infants were coded second by second for infant
      gaze, head orientation, facial expression and self-touch/mouthing behavior.
      Mother behavior was not coded. At 1 year, 27 of these infants were classified as
      secure (B), and 8 as avoidant (A) attachment in the Ainsworth Strange Situation.
      Compared with the B infant, the future A infant spent less time paying 'focused'
      visual attention (a look of a minimum 2 seconds duration) to the mother's face.
      Only if the A infant engaged in self-touch/mouthing behavior did its focused
      visual attention match that of the B. Markovian t to t+1 transition matrices then
      showed that both for future A and for future B infants, focused visual attention
      on the mother constrained the movements of the head to within 60 degrees from
      center vis-a-vis, defining head/gaze co-ordination within an attentional
      interpersonal space. However, infant maintenance of head/gaze co-ordination was
      associated with self-touch/mouthing behavior for the A infant but not the B.
      Positive affect was associated with a disruption of head/gaze co-ordination for
      the A but not the B. Whereas the B had more variable facial behavior, potentially
      providing more facial signaling for the mother, the A had more variable
      tactile/mouthing behavior, changing patterns of self-soothing more often. Thus,
      infants classified as A vs. B at 12 months showed different behavioral patterns
      in face-to-face play with their mothers as early as 4 months.

PMID- 12065028
TI  - Psychotherapeutic work with parents and infants -- psychoanalytic and attachment
      perspectives.
AB  - Psychodynamic psychotherapy with parents and infants addresses the relationship
      between them where there has been a disruption or distortion in the process of
      bonding. Often this is characterized by a repudiation of the state of infancy by
      the parent, and a negation of infantile needs in the baby and in herself. The
      infant joins the mother in co-constructing defensive measures against their
      infantile attachment needs, thereby actualizing intergenerational repetitions.
      The therapist is a clinical observer of the relationship between parent and
      infant and an emotional participant in it. From the behavioural and affective
      interactions, she deduces their emerging mental models and procedures of being
      with each other. Her role is to represent symbolically, for both parent and
      infant, their experience of being with the other. Through this the affective
      dialogue is elaborated, to include feeling and thought constellations that were
      previously enacted procedurally. The paper illustrates these ideas about the
      therapeutic process through transcripts of case material.

PMID- 12065029
TI  - Individual differences in children's understanding of emotion: the roles of
      attachment and language.
AB  - There is accumulating evidence of a relationship between secure attachment and
      children's understanding of emotion (Fonagy & Target, 1997; Harris, 1999). The
      current experiment asked if this relationship is particularly evident when the
      test of emotion understanding includes attachment-related material or is equally
      marked on tests with and without attachment-related material. Children ranging
      from 3-6 years were given a novel test of emotion understanding (the Mother
      Infant Separation Test Video) that incorporated provocative attachment themes and
      also an affectively neutral test of emotion understanding. They performed quite
      consistently on both types of test-either passing both or failing both. In
      addition, attachment security, measured concurrently by means of the Separation
      Anxiety Test, contributed to a correct performance on both tests. This
      contribution remained when other individual differences were controlled for (age,
      verbal mental age and gender). Possible explanations of the relationship between
      attachment and emotion understanding are discussed.

PMID- 12065030
TI  - Parent--child emotion communication, attachment, and affective narratives.
AB  - Forty-four pre-schoolers (ages 4.3 to 5.8 years) and their primary caregivers
      participated in a study on the connections between parent-child emotion
      communication and a narrative assessment of pre-schoolers' attachment. Children
      completed the Separation Anxiety Test (SAT), a narrative assessment of children's
      responses to attachment-related separations (including self-reliance, avoidance,
      attachment and coherence scores). Several aspects of parent-child discussions of
      emotion-eliciting events were also assessed in the Emotion Communication Task.
      Results indicated that SAT coherence was positively related to SAT attachment and
      negatively related to SAT avoidance. Furthermore, SAT coherence was positively
      related to parental scaffolding and negatively related to parental and child
      negativity during the Emotion Communication Task. Parental scaffolding and child
      reciprocity were positively related to each other and, in general, were
      negatively related to parental and child negativity. Discussion focused on the
      potential contributions of children's interactions with caregivers to the
      development of children's attachment narratives and emotion-related
      understanding.

PMID- 12065031
TI  - Attachment in infancy and personal space regulation in early adolescence.
AB  - This study longitudinally assessed associations between secure and ambivalent
      attachment with mothers, fathers and professional caregivers in infancy, and
      personal space regulation and perceived interpersonal competence in 64 early
      adolescents (31 boys, 33 girls). Children classified as ambivalently attached to
      their mothers and/or professional caregivers in infancy displayed significantly
      larger permeability of personal space as compared with children classified as
      securely attached. Attachment classifications with fathers were not associated
      with personal space behavior at 12 years of age. Children who had an insecure
      attachment relationship with both the mother and the professional caregiver in
      infancy displayed smaller personal space boundaries, and tolerated larger
      intrusions into their personal space as compared with children who had two secure
      attachments in infancy. Finally, perceived interpersonal competence was
      positively correlated with personal space permeability.

PMID- 12065032
TI  - Adult attachment and preparing to provide care for older relatives.
AB  - A normative developmental task of middle-aged adults is to consider older family
      members' care needs. Preparing for future caregiving responsibilities may be an
      important way to prevent excessive stress responses when the caregiver role is
      taken on. The present study investigates the extent to which attachment style and
      dimensions of attachment insecurity predict whether middle-generation adults
      prepare for possible future caregiving responsibilities, feel prepared for these
      responsibilities and are satisfied with their preparation activities. Middle
      generation parents of undergraduate students (N = 141) were sent questionnaires
      assessing adult attachment style, attachment insecurity, preparation for future
      care activities, feelings of preparedness, and satisfaction with preparation.
      Results suggest that secure attachment style and lower attachment insecurity had
      limited associations with preparation activities, whereas the associations with
      feelings of preparedness were more robust. Moreover, attachment variables predict
      feelings of preparedness even after controlling for the influence of actual
      preparation behaviors. Separate analyses for individuals already providing care
      vs. those not yet providing care suggest that secure attachment may be more
      important in predicting preparation activities for individuals not yet providing
      care.

PMID- 12065033
TI  - The Circle of Security project: attachment-based intervention with caregiver-pre
      school child dyads.
AB  - The Circle of Security intervention protocol is a 20-week, group-based, parent
      education and psychotherapy intervention designed to shift patterns of attachment
      caregiving interactions in high-risk caregiver-child dyads to a more appropriate
      developmental pathway. All phases of the protocol, including the pre- and post
      intervention assessments, and the intervention itself, are based on attachment
      theory and procedures, current research on early relationships, and object
      relations theory. Using edited videotapes of their interactions with their
      children, caregivers are encouraged: 1. to increase their sensitivity and
      appropriate responsiveness to the child's signals relevant to its moving away
      from to explore, and its moving back for comfort and soothing; 2. to increase
      their ability to reflect on their own and the child's behavior, thoughts and
      feelings regarding their attachment-caregiving interactions; and 3. to reflect on
      experiences in their own histories that affect their current caregiving patterns.
      In this paper we describe the conceptual background of the protocol, and the
      protocol itself. We then present a case study from our current data set of 75
      dyads who have completed the protocol.

PMID- 12065034
TI  - The arthropod Offacolus kingi (Chelicerata) from the Silurian of Herefordshire,
      England: computer based morphological reconstructions and phylogenetic
      affinities.
AB  - The small, non-biomineralized, three-dimensionally preserved arthropod Offacolus
      kingi Orr et al. from the Wenlock Series (Silurian) of Herefordshire, England, is
      re-evaluated, and the new family Offacolidae erected. This new study is based on
      specimens which have been serially ground, reconstructed by computer and rendered
      in the round as coloured models. Offacolus possesses a prosomal appendage array
      similar to that of Limulus, but also bears robust and setose exopods on
      appendages II-V which are unlike those found in any other arthropods.
      Opisthosomal appendages are similar in number and morphology to the book-gills of
      Limulus. Cladistic analysis places Offacolus basally within the Chelicerata, as a
      sister taxon to the eurypterids and extant chelicerates, but more derived than
      the Devonian Weinbergina.

PMID- 12065035
TI  - Endolithic algae: an alternative source of photoassimilates during coral
      bleaching.
AB  - Recent reports of worldwide coral bleaching events leading to devastating coral
      mortality have caused alarm among scientists and resource managers. Differential
      survival of coral species through bleaching events has been widely documented. We
      suggest that among the possible factors contributing to survival of coral species
      during such events are endolithic algae harboured in their skeleton, providing an
      alternative source of energy. We studied the dynamics of photosynthetic pigment
      concentrations and biomass of endoliths in the skeleton of the encrusting coral
      Oculina patagonica throughout a bleaching event. During repeated summer bleaching
      events these endolithic algae receive increased photosynthetically active
      radiation, increase markedly in biomass, and produce increasing amounts of
      photoassimilates, which are translocated to the coral. Chlorophyll concentrations
      and biomass of endoliths were 4.6 +/- 1.57 and 1570 +/- 427 microg cm(-2)
      respectively, in skeletons of relatively healthy colonies (0-40% bleaching) but
      up to 14.8 +/- 2.5 and 4036 +/- 764 microg cm(-2) endolith chlorophyll and
      biomass respectively, in skeletons of bleached colonies (greater than 40%
      bleaching). The translocation dynamics of (14)C-labelled photoassimilates from
      the endoliths to bleached coral tissue showed significantly higher 14C activity
      of the endoliths harboured within the skeletons of bleached corals than that of
      the endoliths in non-bleached corals. This alternative source of energy may be
      vital for the survivorship of O. patagonica, allowing gradual recruitment of
      zooxanthellae and subsequent recovery during the following winter.

PMID- 12065036
TI  - How aphids lose their marbles.
AB  - Insects provide examples of many cunning stratagems to cope with the challenges
      of living in a world dominated by surface forces. Despite being the current
      masters of the land environment, they are at constant risk of being entrapped in
      liquids, which they prevent by having waxy and hairy surfaces. The problem is
      particularly acute in an enclosed space, such as a plant gall. Using secreted wax
      to efficiently parcel and transport their own excrement, aphids were able to
      solve this problem 200 Myr ago. Here, we report on the physical and physiological
      significance of this ingenious solution. The secreted powdery wax has three
      distinct roles: (i) it is hydrophobic, (ii) it creates a microscopically rough
      inner gall surface made of weakly compacted wax needles making the gall ultra
      hydrophobic, and (iii) it coats the honeydew droplets converting them into liquid
      marbles, that can be rapidly and efficiently moved.

PMID- 12065037
TI  - Genetic and environmental determinants of malaria parasite virulence in
      mosquitoes.
AB  - Models of malaria epidemiology and evolution are frequently based on the
      assumption that vector-parasitic associations are benign. Implicit in this
      assumption is the supposition that all Plasmodium parasites have an equal and
      neutral effect on vector survival, and thus that there is no parasite genetic
      variation for vector virulence. While some data support the assumption of
      avirulence, there has been no examination of the impact of parasite genetic
      diversity. We conducted a laboratory study with the rodent malaria parasite,
      Plasmodium chabaudi and the vector, Anopheles stephensi, to determine whether
      mosquito mortality varied with parasite genotype (CR and ER clones), infection
      diversity (single versus mixed genotype) and nutrient availability. Vector
      mortality varied significantly between parasite genotypes, but the rank order of
      virulence depended on environmental conditions. In standard conditions, mixed
      genotype infections were the most virulent but when glucose water was limited,
      mortality was highest in mosquitoes infected with CR. These genotype-by
      environment interactions were repeatable across two experiments and could not be
      explained by variation in anaemia, gametocytaemia, blood meal size, mosquito body
      size, infection rate or oocyst burden. Variation in the genetic and environmental
      determinants of virulence may explain conflicting accounts of Plasmodium
      pathogenicity to mosquitoes in the malaria literature.

PMID- 12065039
TI  - Female choice depends on size but not symmetry of dorsal eyespots in the
      butterfly Bicyclus anynana.
AB  - The eyespots on the ventral wings of Bicyclus anynana butterflies are exposed
      when at rest and interact with predators. Those on the dorsal surface are not
      exposed in this way, and may be involved in courtship and mate choice. In this
      study, we examined whether the size and fluctuating asymmetry (FA) of dorsal
      eyespots are reliable signals of male quality. High developmental stability is
      considered to result in low FA, and to be associated with high quality.
      Individuals of high quality are predicted to produce sexually selected traits
      that are large and symmetrical, at a relatively low cost. In this study, we
      manipulated eyespot development to uncouple eyespot size and FA in order to
      examine their independent roles in signalling to the female. Individual females
      in cages were given the choice between two or three males differing in eyespot
      traits. The results indicate that although size per se of the eyespots is used as
      a signal, FA and wing size are not. We discuss the use of FA in studies of sexual
      selection and aspects of sexual selection on dorsal eyespot size.

PMID- 12065038
TI  - Attentional processes link perception and action.
AB  - Behavioural studies on normal and brain-damaged individuals provide convincing
      evidence that the perception of objects results in the generation of both visual
      and motor signals in the brain, irrespective of whether or not there is an
      intention to act upon the object. In this paper we sought to determine the basis
      of the motor signals generated by visual objects. By examining how the properties
      of an object affect an observer's reaction time for judging its orientation, we
      provide evidence to indicate that directed visual attention is responsible for
      the automatic generation of motor signals associated with the spatial
      characteristics of perceived objects.

PMID- 12065040
TI  - The evolution of tolerance to deer herbivory: modifications caused by the
      abundance of insect herbivores.
AB  - Although recent evidence indicates that coevolutionary interactions between
      species often vary on a biogeographical scale, little consideration has been
      given to the processes responsible for producing this pattern. One potential
      explanation is that changes in the community composition alter the coevolutionary
      interactions between species, but little evidence exists regarding the occurrence
      of such changes. Here we present evidence that the pattern of natural selection
      on plant defence traits, and the probable response to that selection, are
      critically dependent on the composition of the biotic community. The evolutionary
      trajectory of defence traits against mammalian herbivory in the Ivyleaf morning
      glory (Ipomoea hederacea), and which defence traits are likely to respond to
      selection, are both dependent on the presence or absence of insect herbivores.
      These results indicate that variation in community composition may be a driving
      force in generating geographical mosaics.

PMID- 12065041
TI  - History, environment and social behaviour: experimentally induced cooperative
      breeding in the carrion crow.
AB  - Kin-based cooperative breeding, where grown offspring delay natal dispersal and
      help their parents to rear new young, has a long history in some avian lineages.
      Family formation and helping behaviour in extant populations may therefore simply
      represent the retention of ancestral features, tolerated under current
      conditions, rather than a current adaptive process driven by environmental
      factors. Separating these two possibilities challenges evolutionary biologists
      because of the tight coupling that normally exists between phylogeny and the
      environmental distribution of species and populations. The carrion crow Corvus
      corone corone, which exhibits extreme interpopulational variation in the extent
      of cooperative breeding, with populations showing no delayed dispersal and
      helping at all, provides a unique opportunity for an experimental approach. Here
      we show that offspring of non-cooperative carrion crows from Switzerland will
      remain on the natal territory and express helping behaviour when raised in a
      cooperative population in Spain. When we transferred carrion crow eggs from
      Switzerland to Spain, five out of six transplanted juveniles delayed dispersal,
      and two of those became helpers in the following breeding season. Our results
      provide compelling experimental evidence of the causal relationship between
      current environmental conditions and expression of cooperative behaviour.

PMID- 12065042
TI  - Paternal care and male mate-attraction effort in the European starling is
      adjusted to clutch size.
AB  - In facultative polygynous birds with biparental care, a trade-off may occur
      between male parental care and attraction of additional mates. If there is a cost
      associated with reduced male parental care, the relative benefit of mate
      attraction may be predicted to decrease as the size of a male's clutch or brood
      increases. We tested this prediction in monogamous pairs of facultatively
      polygynous European starlings (Sturnus vulgaris). The larger the clutch, the more
      time the male spent incubating and the less time he spent attracting an
      additional female (i.e. singing near and carrying green nesting material into
      adjacent empty nest-boxes). Reduced paternal incubation resulted in lower overall
      incubation (the female did not compensate) and lower hatching success.
      Immediately after experimental reduction of clutches, males spent significantly
      less time incubating and more time singing and carrying greenery, and vice versa
      for experimentally enlarged clutches. Males with experimentally reduced clutches
      attracted a second female more often than males with experimentally enlarged
      clutches. This is the first study, to our knowledge, to provide experimental
      evidence for an adjustment of paternal care and male mate-attraction effort to
      clutch size. However, a trade-off between paternal nestling provisioning and mate
      attraction was not revealed, probably due to the absence of unpaired females by
      that time in the breeding season. Experiments showed that the relative
      contribution of the male and female to nestling provisioning was unrelated to
      brood size.

PMID- 12065043
TI  - Extra-pair paternity and egg dumping in birds: life history, parental care and
      the risk of retaliation.
AB  - Molecular techniques have revealed striking variation among bird species in the
      rates of extra-pair paternity (EPP) and intraspecific brood parasitism (IBP). In
      terms of the proportion of broods affected, rates of EPP and IBP vary across
      species from 0-95% and 0-50%, respectively. Despite a plethora of hypotheses and
      several careful comparative analyses, few robust correlates of this interspecific
      variation have been identified. One explanation for this shortfall is that most
      comparative studies have tended to focus on contemporary ecological factors and
      ignored fundamental differences in reproductive biology that evolved millions of
      years ago. We show that, for both EPP and IBP, over 50% of interspecific
      variation is due to differences among taxonomic families and orders. Therefore,
      we test hypotheses that predict interspecific variation in the rate of
      alternative reproductive strategies should be associated with differences in life
      history and the form of parental care. Our analyses largely support these
      predictions, with high rates of reproductive cheating being associated with
      'fast' life histories. High EPP rates are associated with high rates of adult
      mortality and reduced paternal care. High IBP rates are associated with high
      fecundity rates. These patterns remain intact whether we use species as
      independent data points or evolutionary contrasts based on either molecular or
      morphological phylogenies. These results are interpreted as supporting the idea
      that alternative reproductive strategies are most common in taxa in which the
      risks of retaliation are low. We suggest a hierarchical explanation for
      interspecific variation in the incidence of alternative reproductive strategies.
      Variation between major avian lineages in the EPP and IBP rates are determined by
      fundamental differences in life history and parental care that evolved many
      millions of years ago. Variation between populations or individuals of the same
      species, however, are more likely to be determined by differences in contemporary
      ecological and genetic factors.

PMID- 12065044
TI  - Ecomorphological analysis of trophic niche partitioning in a tropical savannah
      bat community.
AB  - The exceptional diversity of neotropical bat communities is sustained by an
      intricate partitioning of available resources among the member species. Trophical
      specialization is considered an important evolutionary avenue towards niche
      partitioning in neotropical phyllostomid bats. From an ancestral insectivorous
      condition, phyllostomids evolved into highly specialized frugivorous,
      carnivorous, nectarivorous, piscivorous and even sanguivorous species.
      Previously, correlations between cranial morphology and trophic ecology within
      this group have been documented. Here, we examine the evolutionary relationships
      between bite force and head shape in over 20 species of bats from a single
      tropical savannah bat community. The results show that bite force increases
      exponentially with body size across all species examined. Despite the significant
      differences between large dietary groups using traditional analysis (i.e. non
      phylogenetic) and the strong evolutionary correlations between body mass and bite
      force, phylogenetic analyses indicated no differences in bite performance between
      insectivorous, omnivorous and frugivorous bats. Comparisons of three species with
      highly specialized feeding habits (nectarivory, piscivory and sanguivory) with
      the rest of the species in the community indicate that specialization into these
      niches comes at the expense of bite performance and, hence, may result in a
      reduction of the trophic niche breadth.

PMID- 12065045
TI  - Are most species small? Not within species-level phylogenies.
AB  - The robust macro-ecological observation that there are more small-bodied species
      implies that small-bodied organisms have experienced elevated net rates of
      diversification. We investigate the role of body size in creating non-random
      differences in rates of cladogenesis using a set of 38 species-level phylogenies
      drawn from a range of animal groups. We use independent contrasts to explore the
      relationship between body size and species richness within individual phylogenies
      and across related sets of phylogenies. We also carry out a meta-analysis looking
      for associations between body size and species richness across the taxa. We find
      little evidence for increased cladogenesis among small-bodied organisms within
      taxa, and no evidence for any consistent differences between taxa. We explore
      possible explanations for the inconsistency of our findings with macro-ecological
      patterns.

PMID- 12065046
TI  - Sympatric populations of the highly cross-fertile coral species Acropora
      hyacinthus and Acropora cytherea are genetically distinct.
AB  - High cross-fertilization rates in vitro and non-monophyletic patterns in
      molecular phylogenies challenge the taxonomic status of species in the coral
      genus Acropora. We present data from eight polymorphic allozyme loci that
      indicate small, but significant, differentiation between sympatric populations of
      Acropora cytherea and Acropora hyacinthus (F(ST) = 0.025-0.068, p < 0.05), a pair
      of acroporid corals with very high interspecific fertilization rates in vitro.
      Although no fixed allelic differences were found between these species, the
      absence of genetic differentiation between widely allopatric populations suggests
      that allele frequency differences between A. cytherea and A. hyacinthus in
      sympatry are biologically significant. By contrast, populations of Acropora
      tenuis, a species which spawns 2-3 hours earlier and shows low cross
      fertilization rates with congeners in vitro, were clearly distinct from A.
      cytherea and A. hyacinthus (F(ST) = 0.427-0.465, p < 0.05). Moreover, allopatric
      populations of A. tenuis differed significantly, possibly as a consequence of its
      relatively short period of larval competency. Our results effectively rule out
      the possibility that A. hyacinthus and A. cytherea are morphotypes within a
      single species, and indicate that hybridization occurs relatively infrequently
      between these taxa in nature.

PMID- 12065048
TI  - The evolution of parasites from their hosts: intra- and interspecific parasitism
      and Emery's rule.
AB  - In some taxa of Hymenoptera, fungi, red algae and mistletoe, parasites and their
      hosts are either sibling species or at least closely related (Emery's rule).
      Three evolutionary mechanisms have been proposed for this phenomenon: (i)
      intraspecific parasitism is followed by sympatric speciation; (ii) allopatric
      speciation is followed by secondary sympatry and the subsequent parasitism of one
      sibling species by the other; and (iii) allopatric speciation of a species with
      intraspecific parasitism is followed by secondary sympatry, in which one species
      becomes an obligate parasite of the other. Mechanisms (i) and (ii) are
      problematic, while mechanism (iii) has not, to our knowledge, been analysed
      quantitatively. In this paper, we develop a model for single- and two-species
      evolutionary stable strategies (ESSs) to examine the basis for Emery's rule and
      to determine whether mechanism (iii) is consistent with ESS reasoning. In
      secondary sympatry after allopatric speciation, the system's evolution depends on
      the relative abundances of the two sibling species and on the proportional damage
      wrought by parasites of each species on non-parasitic members of the other.
      Depending on these interspecific effects, either the rarer or the commoner
      species may become the parasite and the levels of within-species parasitism need
      not determine which evolves to obligate parasitism.

PMID- 12065047
TI  - Regulation of reproduction in a queenless ant: aggression, pheromones and
      reduction in conflict.
AB  - In the monogynous queenless ant Diacamma ceylonense, the future reproductive
      (future gamergate) is very aggressive towards infertile workers during the first
      days of her adult life. Overt aggression disappears at about three weeks, when
      the future gamergate begins to lay male-destined eggs and is ready to mate. Over
      the same period, her cuticular hydrocarbon profile alters, changing from a
      chemical signature similar to that of a sterile worker towards that of a
      gamergate. In nature, these behavioural and chemical changes will coincide with a
      reduction in conflict within the nest: faced with a virgin future gamergate,
      infertile workers have an interest in producing male-destined eggs; however, once
      the gamergate produces female eggs, they have an interest in rearing her
      offspring. This demonstration of a shift from physical inhibition to chemical
      signalling is interpreted in terms of sociogenetic theory, the role of cuticular
      hydrocarbons as an indicator of fertility in insects and the fact that the
      regulation of reproduction in Diacamma involves mechanisms redolent of both
      queenless and queenright ant species.

PMID- 12065049
TI  - Significant large-scale chromosome territory movement occurs as a result of
      mitosis, but not during interphase.
AB  - PURPOSE: To investigate large-scale relative movement (position change) of
      interphase chromosome territories (ICT), as indicated by the separation of
      chromosome derivatives following exposure to ionizing radiation. MATERIALS AND
      METHODS: A simple experiment was conducted to investigate large-scale movement of
      ICT, using whole chromosome 18 painting to measure the frequency of fluorescent
      ICT in irradiated lymphocytes, cultured over 9 days (seven cell cycles). After
      chromosome 18 painting, derivative chromosome territory separation was indicated
      by the observation of three fluorescent ICT in aberrant cells compared with the
      presence of two fluorescent ICT in normal cells. The frequencies of interphase
      nuclei containing three fluorescent chromosome territories for unirradiated
      resting lymphocytes and for lymphocytes acutely irradiated with 2.25 or 5.5 Gy
      137Cs gamma-rays were measured for each culture time point of 0, 1, 2, 3, 4, 7
      and 9 days. RESULTS: No significant difference was observed in the frequency of
      three ICT between the average of the controls and irradiated cells cultured for
      0, 1 and 2 days. However, irradiated cells cultured for >or=3 days showed a
      significant increase in the frequency of three fluorescent ICT over those
      cultured for <or=2 days, as well as over all controls. The frequency of cells
      containing three territories for cultures that received a dose of 5.5 Gy was
      about twice that for cultures that received a dose of 2.25 Gy for 3-, 4-, 7- and
      9-day cultures. CONCLUSION: The finding that significant large-scale movement was
      not observed within the first 48 h of cell culture, but was seen in cultures
      after 48 h, suggests that ICT do not undergo large-scale movement relative to
      each other until lymphocytes go through mitosis.

PMID- 12065050
TI  - DNA lesion complexity and induction of apoptosis by ionizing radiation.
AB  - PURPOSE: To determine whether murine lymphoid cell lines can discriminate between
      high- and low-LET (linear energy transfer) radiation-induced DNA lesions.
      MATERIALS AND METHODS: Sensitivity to killing by DNA-incorporated 3H and 125I
      decays, accumulated during storage in the gas phase of a liquid nitrogen tank,
      was determined by clonogenic survival assay. RESULTS: Induction of a lethal event
      in the STRij-4-2.2, WEHI-22.1, and L5178Y-R cell lines required approximately 30
      times more 3H than 125I decays. Hence, the same ratio of 3H to 125I decays was
      found irrespective of whether the cell lines contained mutant or wild-type p53
      and irrespective of whether they underwent rapid interphase or mitosis-related
      apoptosis after irradiation. The 18-81 cell line differed in showing a ratio of
      around 21 and it is argued that this may be a consequence of v-ABL over
      expression. The assumption that DNA-incorporated 3H and 125I decays are low- and
      high-LET-like events respectively was confirmed by the similar sensitivity of
      L5178Y-R and -S cells to killing by 125I decays in contrast with their difference
      in sensitivity to 3H decays. CONCLUSIONS: The difference in lethal effectiveness
      between DNA-incorporated 3H and 125I decays can be explained by the hypothesis
      that simple DSB (double-strand breaks) are non-lethal and that cell killing is
      attributable to complex DSB. The low-LET radiation-specific sensitization of
      L5178Y-S cells may reflect defective repair of a DNA lesion class (presumably
      simple DSB) that is differentially induced by high- and low-LET radiation and is
      non-lethal to cells with normal repair capacity.

PMID- 12065051
TI  - Model for the initiation of ionizing radiation-induced apoptosis in lymphoid
      cells by complex DNA double-strand breaks.
AB  - PURPOSE: To present a model for the molecular events that lead to the induction
      of apoptosis in irradiated lymphoid cells based on the assumption that the
      process is triggered by complex DNA double-strand breaks (DSB). OUTLINE OF THE
      MODEL: * Cellular DNA repair mechanisms have difficulty rejoining complex DSB
      because of the nature of the end groups on such breaks. * Association between p53
      and DNA topoisomerase I (topo I) can occur at complex DSB in open regions of the
      genome and the enzymic activity of such associations is not suppressed by polyADP
      ribosylation. * Binding of p53 and topo I at a complex DSB results in the
      transient trapping of a DNA-topo I cleavage complex. * Transiently trapped DNA
      topo I cleavage complexes at complex DSB are reversed following association with
      topo I bound elsewhere in the genome, thus initiating a misrejoining event. *
      Topo I-mediated DNA misrejoining creates a structure that activates p53.
      Initiation of rapid interphase apoptosis requires that the inducing signal from
      activated p53 exceeds a threshold level. * Initiation of rapid interphase
      apoptosis is regulated by poly(ADP-ribose) polymerase.

PMID- 12065052
TI  - DNA fragmentation in V79 cells irradiated with light ions as measured by pulsed
      field gel electrophoresis. I. Experimental results.
AB  - PURPOSE: To compare the results on DNA fragmentation induced in Chinese hamster
      V79 cells by various doses of gamma-rays and low-energy protons and helium-4
      ions. MATERIALS AND METHODS: V79 cells were irradiated as monolayers with
      monoenergetic protons and helium-4 ions; gamma-rays were used as the reference
      radiation. DNA double-strand breaks were evaluated by calibrated pulsed-field gel
      electrophoresis using conditions covering the range 5.7 Mbp-23.1 kbp. RESULTS:
      The fragment-counting method gave double-strand breaks yields and the relative
      biological effectiveness higher than those obtained by the fraction of activity
      released method. The frequency distribution of fragments showed that protons and
      helium ions induced more fragments below the Mbp region than did gamma-rays at
      the same dose. The distributions for both the irradiated and non-irradiated
      samples clearly appeared to be non-random. CONCLUSION: Differences were observed
      in the yield and spatial correlation, at a molecular size scale characteristic of
      loop dimensions, of the double-strand breaks induced by gamma-rays and by light
      ions. These effects may have a role in the observed different cell response to
      these radiations.

PMID- 12065053
TI  - Identification of genes differentially expressed in V79 cells grown as multicell
      spheroids.
AB  - PURPOSE: Growth of Chinese hamster V79 cells as multicell spheroids leads to an
      increase in resistance to killing by ionizing radiation and etoposide.
      Differential display was used to identify changes in gene expression that occur
      when cells are grown as spheroids. MATERIALS AND METHODS: Differential display
      was performed using exponentially growing Chinese hamster V79 cells and the outer
      cell layer of V79 spheroids. Using six different pairs of primers, 20 altered
      bands were selected. Eight genes, confirmed using reverse Northerns, showed a
      match in a GenBank search. Antibodies against a calcium-binding protein, mts1,
      confirmed differential expression of this protein. Intracellular free calcium
      levels were measured using fluo-3 fluorescence, and the effect of a calcium
      binding agent on etoposide resistance was examined using the comet assay.
      RESULTS: Genes upregulated in the outer cell layer of spheroids relative to
      monolayers included: (1) mts1 (S100A4), a calcium binding protein implicated in
      proliferation, metastasis, cell adhesion, and angiogenesis; (2) cytochrome c
      oxidase II; (3) B-ind1, a mediator of Rac-1 signaling; (4) TRAM, an endoplasmic
      reticulum protein. Genes downregulated in spheroids were: (5) phosphoglycerate
      kinase; (6) ARL-3, a ras-related GTP binding protein; (7) MHC class III
      complement 4A; and (8) 2,4-dienoyl-CoA. Immunohistochemistry confirmed
      overexpression of mts1 and another calcium-binding protein, calreticulin, in V79
      outer spheroid cells relative to monolayers. C6 rat glioma and SiHa human
      cervical carcinoma cells that demonstrate a contact effect also showed
      upregulation of mts1 or calreticulin, while WiDr colon carcinoma cells that lack
      contact resistance showed no change in expression of either calcium binding
      protein. Intracellular free calcium levels were found to be almost two times
      lower in the outer cells of V79 spheroids compared to monolayers. V79 monolayer
      and outer spheroid cells treated with the calcium chelating agent BAPTA-AM showed
      a similar level of DNA damage by etoposide. CONCLUSIONS: Expression of genes
      involved in calcium binding, signaling and metabolism are differentially
      expressed when V79 cells are grown as spheroids. Differences in the levels of
      intracellular calcium may underlie the contact effect.

PMID- 12065054
TI  - Indomethacin lowers the threshold thermal exposure for hyperthermic
      radiosensitization and heat-shock inhibition of ionizing radiation-induced
      activation of NF-kappaB.
AB  - PURPOSE: It is well established that salicylate and several other non-steroidal
      anti-inflammatory agents (NSAID), including indomethacin, can activate the heat
      shock response, albeit at high concentrations. This is significant since heat
      shock significantly alters the cellular cytotoxic response to ionizing radiation
      (IR). It was previously shown that heat shock, as well as NSAIDs, inhibits IR
      induced activation of NF-kappaB and that NF-kappaB protects against IR-induced
      cytotoxicity. Hence, it is hypothesized that pretreatment with indomethacin
      before heating will lower the temperature and heating times required to inhibit
      the activation of NF-kappaB and induce significant hyperthermic
      radiosensitization. MATERIALS AND METHODS: Experiments were performed in HeLa
      cell lines and the DNA-binding activity was determined by EMSA. Cellular
      radiosensitivity was determined by clonogenic assay. RESULTS: HeLa cells
      pretreated with indomethacin showed a decrease in the temperature-time
      combination necessary to inhibit IR-induction of NF-kappaB DNA binding. In
      addition, clonogenic cell survival assays using identical conditions showed an
      indomethacin dose-dependent enhancement of hyperthermic radiosensitization. Thus,
      similar concentrations of indomethacin both lowered the threshold thermal
      exposure to inhibit activation of NF-kappaB DNA-binding and increased the
      sensitivity of tumour cells to hyperthermic radiosensitization-induced
      cytotoxicity. In HeLa cells treated with N-alpha-tosylphenylalanyl-chloromethyl
      ketone (TPCK), a serine protease inhibitor that blocks activation of NF-kappaB,
      an increase in radiosensitivity was observed. Interestingly, no additional cell
      killing was observed when heat shock was added to cells treated with TPCK before
      IR, suggesting a possible common cytotoxic pathway. CONCLUSIONS: The results
      demonstrate that indomethacin lowers the temperature-time conbination necessary
      to induce several physiological processes associated with the heat-shock
      response. Furthermore, NSAID may be potential adjuvants in improving the clinical
      effectiveness of hyperthermia in radiation therapy.

PMID- 12065055
TI  - Roles of DNA-dependent protein kinase and ATM in cell-cycle-dependent radiation
      sensitivity in human cells.
AB  - PURPOSE: The roles of DNA-dependent protein kinase (DNA-PK) and ATM in the cell
      cycle-dependent radiosensitivity in human cells were investigated. METHODS AND
      MATERIALS: A DNA-PK activity-deficient human glioblastoma cell line M059J, ataxia
      telangiectasia cell lines AT3BISV and AT5BIVA, and control cell lines were used.
      Wortmannin inhibited DNA-PK and ATM activities. Cells were synchronized by
      hydroxyurea. Progression through the cell cycle was analysed by flow cytometry.
      RESULTS: M059J exhibited hyper-radiosensitivity throughout the cell cycle, with
      extreme hyper-radiosensitivity in G to early S-phase compared with the control
      cell line M059K. AT3BISV and AT5BIVA exhibited hyper-radiosensitivity throughout
      the cell cycle but showed a similar pattern of cell-cycle-dependent
      radiosensitivity to that observed in LM217 or HeLa cells. In AT3BISV and AT5BIVA,
      radiosensitization by wortmannin was observed throughout the cell cycle and was
      most prominent in G1 to early S-phase. Wortmannin did not sensitize M059J to
      ionizing radiation in any cell-cycle phase. DNA-PK activities were not different
      throughout the cell cycle. CONCLUSION: The results suggest that (1) non
      homologous endjoining plays a dominant role in G1 to early S-phase and a minor
      role in late S to G2-phase in repairing DNA double-strand breaks, (2) the role of
      ATM in repairing double-strand breaks may be almost cell-cycle-independent and
      (3) the dominant role of non-homologous end-joining during G1 to early S-phase is
      not due to cell-cycle-dependent fluctuations in DNA-PK activity.

PMID- 12065056
TI  - Poly ADP-ribosylation in two L5178Y murine lymphoma sublines differentially
      sensitive to DNA-damaging agents.
AB  - PURPOSE: To characterize the response to X-irradiation of the poly ADP
      ribosylation system in two closely related murine lymphoma sublines, L5178Y-R (LY
      R) and L5178Y-S (LY-S), with differential sensitivity to various DNA damaging
      agents (UV-C and ionizing radiation, hydrogen peroxide). MATERIALS AND METHODS:
      LY cells were X-irradiated (2 Gy). NAD+ was determined in cell extracts by high
      pressure liquid chromatography. ADP-ribose polymers were purified and analysed by
      densitometry after polyacrylamide gel electrophoresis. Nuclear matrix proteins
      were separated by SDS-polyacrylamide gel electrophoresis and processed for ADP
      ribose polymer blots to estimate their ability to bind poly(ADP-ribose). RESULTS:
      In the radiosensitive LY-S cells, the constitutive levels of ADP-ribose polymers
      were twofold higher than in radioresistant LY-R cells, but unresponsive to a
      challenge with 2 Gy X-rays. The concentrations of NAD+ - the substrate for
      poly(ADP-ribose) synthesis - were identical in the two cell lines. X-rays (2 Gy)
      depleted NAD+ only in LY-S cells. These cells also produced shorter poly(ADP
      ribose) molecules as compared with LY-R cells. Nuclear matrix preparations of LY
      S cells exhibited lower poly(ADP-ribose)-binding capacity than those of LY-R
      cells. CONCLUSION: The results demonstrate disturbances in the poly ADP
      ribosylation response of the radiosensitive LY-S cells and reduced poly(ADP
      ribose)-binding affinity of the nuclear matrix of these cells.

PMID- 12065057
TI  - Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with
      biodegradable drug (amifostine) pellets.
AB  - PURPOSE: We evaluated the use of a subcutaneously (s.c.) implantable,
      biodegradable pellet as a drug delivery system for the radioprotector amifostine.
      MATERIALS AND METHODS: Mice were implanted s.c. with either the custom-made
      biodegradable amifostine drug pellet or the placebo pellet without amifostine,
      exposed to cobalt-60 gamma-radiation (bilateral, 1 Gy min(-1), 7-16 Gy), and the
      30-day survival rate was monitored. The non-irradiated mouse was used for
      pharmacokinetic and behavioural tests. RESULTS: Significant radioprotection (85
      95% survival) at 10 Gy was observed in the three-amifostine pellet implanted
      group 3-5 h after implantation. LD50/30 was 7.97, 8.74 and 16.64 Gy for the
      control, three-placebo pellet (dose reduction factor, DRF=1.10, p<0.01), and
      three-amifostine pellet (DRF=1.79, p<0.01) groups respectively in mouse exposed
      to radiation 2h after implantation. Radioprotection at 12 Gy was observed up to
      4h after s.c. amifostine administration and up to 3h after implantation.
      Pharmacokinetic data revealed that the three-amifostine pellet group had
      sustained blood WR-1065 levels at 2 h after implantation, in contrast to the
      reported sharp peak at 30 min for s.c. administration. Although locomotor
      activity was significantly reduced (p<0.01) in the amifostine pellet group, the
      onset of the locomotor decrement was delayed as compared with groups that
      received 400 and 750 mg kg(-1) s.c. amifostine. CONCLUSIONS: Amifostine in
      biodegradable implant was effective. The radioprotection observed was comparable
      between conventional s.c. administration of the drug and implantation.
      Pharmacokinetic data and locomotor activity suggest that the implantation was
      beneficial though radioprotection data warrants formulation improvements in
      implants.

PMID- 12065058
TI  - Drug-metabolizing activity of human and rat liver, lung, kidney and intestine
      slices.
AB  - 1. Organ-specific biotransformation was studied in human and rat liver, lung,
      kidney and small intestine slices and compared on a protein basis, using four
      model substances. 2. Deethylation of lidocaine was highest in liver slices from
      both man and rat, followed by the small intestine. 3. Metabolism of testosterone
      was highest in liver slices, but a different overall metabolic pattern was found
      between the different organs. 4. Lung, kidney and intestine slices prepared from
      human and rat organs showed mainly an unknown metabolite of 7-ethoxycoumarin
      identified as 4-ethoxy-2-hydroxyphenyl propionic acid (EPPA). 5. The maximal
      metabolism of 7-ethoxycoumarin in slices was equal with in vivo V(max) in the
      rat. 6. Phase II metabolism of 7-hydroxycoumarin in kidney and intestinal slices
      was about 60% of the activity in liver slices. 7. In conclusion, organs other
      than the liver show a surprisingly high drug-metabolizing activity. Thus, the use
      of precision-cut slices of a combination of drug metabolizing organs in an in
      vitro test system from both animal and human origin is required for a proper
      systematic prediction of drug metabolism in man.

PMID- 12065059
TI  - Inhibition of phenol sulfotransferase (SULT1A1) by quercetin in human adult and
      foetal livers.
AB  - 1. Quercetin is one of the most abundant flavonoids in edible vegetables, fruit
      and wine. The aim was to study the type of inhibition of SULT1A1 by quercetin in
      the human adult and foetal livers. 2. The activity of SULT1A1 was measured with 4
      microM 4-nitrophenol and 0.4 microM 3'-phosphoadenosine-5'-phosphosulphate
      [(35)S], and its mean (+/-SD) and median were 769 +/- 311 and 740 pmol min(-1)
      mg(-1), respectively (adult liver, n = 10), and 185 +/- 98 and 201 pmol min(-1)
      mg(-1), respectively (foetal liver, n = 8, p < 0.0001). 3. In non-inhibited
      samples, K(m) for SULT1A1 (mean +/- SD) was 0.31 +/- 0.14 microM (adult liver)
      and 0.49 +/- 0.17 microM (foetal liver, n.s.). V(max) for SULT1A1 (mean +/- SD)
      was 885 +/- 135 pmol min(-1) mg(-1) (adult liver) and 267 +/- 93 pmol min(-1) mg(
      1) (foetal liver, p = 0.007). 4. The IC(50) of quercetin for SULT1A1 was measured
      in three samples of adult and foetal livers and was 13 +/- 2.1 and 12 +/- 1.4 nM,
      respectively. 5. The type of inhibition was mixed non-competitive in adult and
      foetal livers and K(i) was 4.7 +/- 2.5 nM (adult liver) and 4.8 +/- 1.6 nM
      (foetal liver). 6. In the adult liver, the intrinsic clearance (mean +/- SD) was
      3.3 +/- 1.5 ml min(-1) mg(-1) (non-inhibited samples), 0.9 +/- 0.4 ml min(-1) mg(
      1) (12.5 nM quercetin) and 0.5 +/- 0.06 ml min(-1) mg(-1) (25 nM quercetin). In
      the foetal liver, the intrinsic clearance (mean +/- SD) was 0.5 +/- 0.2 ml min(
      1) mg(-1) (non-inhibited samples), 0.12 +/- 0.01 ml min(-1) mg(-1) (12.5 nM
      quercetin) and 0.2 +/- 0.09 ml min(-1) mg(-1) (25 nM quercetin). 7. In
      conclusion, quercetin is a potent inhibitor of human adult and foetal liver
      SULT1A1. It reduces the sulphation rate and intrinsic clearance of 4-nitrophenol
      in both human adult and foetal livers. This suggests that quercetin may inhibit
      the sulfation rate of those drugs sulphated by SULT1A1. The inhibition of SULT1A1
      is complex and not due solely to competition at the catalytic site of SULT1A1.

PMID- 12065060
TI  - Tissue disposition, excretion and metabolism of 2,2',4,4',5-pentabromodiphenyl
      ether (BDE-99) in the male Sprague-Dawley rat.
AB  - 1. A disposition, metabolism and excretion study of orally administered
      2,2',4,4',5-pentabromodiphenyl ether (BDE-99) was conducted in the conventional
      and bile duct-cannulated male rat. 2. In the conventional rat, >50% of the
      radiolabelled dose was retained at 72 h, and lipophilic tissues were the
      preferred sites for disposition, i.e. adipose tissue, adrenals, gastrointestinal
      tract and skin. 3. Urinary excretion of BDE-99 was very low (<1% of dose), and
      glucuronidation of phenolic metabolites was suggested. 4. Biliary excretion of
      BDE-99 was slightly greater than observed in urine, i.e. 3.6% at 72 h. 5. Over
      43% of the dose in the conventional male rat and 86% in the bile duct-cannulated
      rat was excreted in the faeces, mainly as the unmetabolized parent compound. 6.
      Metabolites in bile and faeces were not conjugated. Mono- and di-hydroxylated
      pentabromodiphenyl ether metabolites were characterized by mass spectrometry. Two
      thiol metabolites were characterized in the bile. Oxidative debromination was
      also observed in the faecal metabolites. 7. Tissue BDE-99 was readily
      extractable, except for in the liver. The tissue (14)C was not associated with
      lipids and was mainly the unmetabolized parent compound. 8. Total thyroxine (T4)
      plasma levels were elevated at 3 and 6 days, and returned to control levels by
      day 12.

PMID- 12065061
TI  - Microsomal metabolism and enzyme kinetics of the terpene p-cymene in the common
      brushtail possum (Trichosurus vulpecula), koala (Phascolarctos cinereus) and rat.
AB  - 1. p-Cymene is an aromatic monoterpene found in the leaves of Eucalyptus spp. and
      is ingested in the diet of two marsupial folivores, the brushtail possum
      (Trichosurus vulpecula) and koala (Phascolarctos cinereus). The metabolism of p
      cymene by liver microsomes from the possum, koala and rat (an animal whose diet
      is not terpene-rich) was examined. 2. The major p-cymene metabolite in each
      species was cuminyl alcohol, with smaller amounts of other side-chain alcohols
      being formed. No phenolic metabolites were detected. Possum and koala microsomes
      further oxidized cuminyl alcohol to cumic acid. 3. Pretreatment with a terpene
      diet more than doubled the V(max) for cuminyl alcohol formation by possum
      microsomes. This is similar to a previous finding by our group with 1,8-cineole
      and indicates that a terpene-containing diet results in induction of the enzymes
      responsible for terpene metabolism. 4. The rank order of the ability to
      metabolize p-cymene, measured by intrinsic clearance (Cl(int) = V(max)/K(m)
      [microl mg protein(-1) min(-1)]) was: terpene-treated possum (128)>control possum
      (107)>koala (69)>rat (38). 5. The findings support the hypothesis that animals
      that have adapted to a diet of Eucalypus leaf have a greater capacity than
      generalist feeders to metabolize dietary terpenes.

PMID- 12065062
TI  - Long-term disposition of a novel lipophilic platinum complex SM-11355 in dog
      after intrahepatic arterial administration: highly sensitive detection of
      platinum and radioactivity.
AB  - 1. The disposition of SM-11355, an anticancer platinum complex for hepatocellular
      carcinoma, was investigated in dog by measuring platinum (Pt) and radioactivity
      levels following intrahepatic arterial administration of (14)C-SM-11355 suspended
      in Lipiodol, an oily lymphographic agent. Plasma and excretion profiles were
      monitored in six animals, with tissue distribution studied after 1 day, 4 and 13
      weeks (n = 2/time point). 2. SM-11355 was released very slowly into the systemic
      circulation from Lipiodol, resulting in very low levels of Pt compounds in
      plasma, urine, faeces and organs. Plasma levels of Pt and radioactivity declined
      with apparent half-lives of 5-7 weeks. Excretion continued even at 3 months after
      the administration with proportions excreted for Pt and radioactivity up to 30
      60% in urine and 8-10% in faeces. 3. The Pt and radioactivity in the liver
      accounted for 80-100% of the dose at 1 day and for 20-50% at 13 weeks after the
      administration, predominately as intact SM-11355. The concentrations were highest
      in the left lobe of the liver, the administration site, but levels in the
      remainder of the liver were also markedly higher than those in plasma and other
      tissues. 4. The results strongly support the concept that SM-11355 targets the
      liver with highly selectivity and sustained release of Pt compounds.

PMID- 12065063
TI  - Metabolism of the analgesic drug ULTRAM (tramadol hydrochloride) in humans: API
      MS and MS/MS characterization of metabolites.
AB  - 1. Metabolism of the analgesic agent tramadol hydrochloride has been investigated
      after a single oral administration of tramadol to three male volunteers (100
      mg/subject), and a urine pool (4-12h) was obtained. 2. Unchanged tramadol and a
      total of 23 metabolites, consisting of 11 Phase I metabolites (M1-11) and 12
      conjugates (seven glucuronides, five sulphates), were profiled, characterized and
      tentatively identified in urine on the basis of API ionspray-MS and MS/MS data.
      3. Of the metabolites, five (M1-5) had been previously identified. 4. The
      metabolites were formed via the following six metabolic pathways: (1) O
      demethylation, (2) N-demethylation, (3) cyclohexyl oxidation, (4) oxidative N
      dealkylation, (5) dehydration and (6) conjugation. 5. Pathways 1-3 appear to be
      major routes, forming seven O-desmethyl/N-desmethyl and hydroxycyclohexyl
      metabolites. 6. Pathways 1-3 in conjunction with pathway 6 produced seven
      glucuronides along with five sulphates. 7. In addition, the in vitro metabolism
      of tramadol was conducted using a human liver microsomal fraction in the presence
      of an NADPH-generating system. Unchanged tramadol (82% of the sample) plus eight
      metabolites (M1, M2, M4-6, tramadol-N-oxide (M31), OH-cyclohexyl-M1 (M32) and
      dehydrated tramadol-N-oxide), were profiled and tentatively identified on the
      basis of MS and MS/MS data.

PMID- 12065064
TI  - Hydromorphone metabolites: isolation and identification from pooled urine samples
      of a cancer patient.
AB  - 1. Hydromorphone-3-glucuronide, dihydromorphine, dihydroisomorphine,
      dihydromorphine-3-glucuronide and dihydroisomorphine-3-glucuronide were isolated
      from a cancer patient's urine and identified as metabolites of hydromorphone by
      comparison with synthetic standards using LC/MS/MS with gradient elution. 2. The
      relative urinary recovery of dihydroisomorphine-3-glucuronide was estimated to be
      17-fold higher than previously reported. 3. Three new metabolites, including
      hydromorphone-3-sulphate, norhydromorphone and nordihydroisomorphine, were
      tentatively identified.

PMID- 12065065
TI  - Pharmacokinetic analysis of factors determining elimination pathways for sulfate
      and glucuronide metabolites of drugs. I: studies by in vivo constant infusion.
AB  - 1. The hepatic and renal handling of glucuronides and sulphates of three phenolic
      compounds, 4-methylumbelliferone (4-MU), p-nitrophenol (pNP) and acetaminophen
      (APAP), were evaluated pharmacokinetically by in vivo constant infusion
      experiments in rat. It was shown that the urinary excretion rate at steady-state
      was larger than the biliary excretion rate for both glucuronides and sulfates,
      and sulfates, in particular, were extensively excreted into the urine. 2. For
      each glucuronide, however, biliary excretion clearances (CL(b)) calculated based
      on the total concentration and unbound concentration in the liver were much
      larger than the corresponding renal excretion clearances (CL(r)). Even in the
      case of sulfates, there was not any large difference between CL(r) and CL(b)
      based on the total and unbound concentration in tissues, which could not explain
      their extensive urinary excretion. From these results, these excretion clearances
      were recognized not to reflect necessarily the actual excretion rate obtained. 3.
      On the other hand, the tissue-to-plasma concentration ratio (K(p)) of both
      glucuronides and sulfates for every phenolic compound was much higher in the
      kidney than that in the liver. The results suggested that one of the most
      important determinants for the preferential excretion of these conjugates into
      the bile or urine is the extent of disposition of each compound to the liver or
      kidney. 4. In addition, K(p) of both glucuronides and sulfates in the liver,
      where these conjugates are mainly formed, was small. The K(p) of sulfates was
      quite low, suggesting that sulfates generated in the liver were subject to
      extensive sinusoidal efflux.

PMID- 12065066
TI  - Zanamivir for the treatment of influenza in adults: a systematic review and
      economic evaluation.

PMID- 12065067
TI  - A systematic review of discharge arrangements for older people.

PMID- 12065068
TI  - A rapid and systematic review of the clinical effectiveness and cost
      effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine in non-small
      cell lung cancer.
AB  - BACKGROUND: The incidence of lung cancer is declining following a drop in smoking
      rates, but it is still the leading cause of death from cancer in England and
      Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor
      everywhere, but they appear to be better in the rest of the European Community
      and the USA than in the UK. Only about 5 per cent of people with lung cancer
      survive for 5 years, and nearly all of these are cured by surgery after
      fortuitously early diagnosis. At present, only a small proportion of patients
      (probably about 5 per cent) with non-small-cell lung cancer are being given
      chemotherapy. Some centres treat a greater proportion. OBJECTIVES: This review
      examines the clinical effectiveness and cost-effectiveness of four of the newer
      drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating
      the most common type of lung cancer (non-small-cell lung cancer). The first three
      drugs are used for first-line treatment, but at present docetaxel is used only
      after first-line chemotherapy has failed. METHODS: This report was based on a
      systematic literature review and economic modelling, supplemented by cost data.
      RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials
      were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13
      for vinorelbine. The quality of the trials was variable but good overall. There
      was a wide range of comparators. Some trials compared chemotherapy with best
      supportive care (BSC), which involves care that aims to control symptoms, with
      palliative radiotherapy if needed, but not to prolong life. Others compared the
      newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF
      BENEFITS: The gains in duration of survival with the new drugs are modest - a few
      months - but worthwhile in a condition for which the untreated survival is only
      about 5 months. There are also gains in quality of life compared with BSC,
      because on balance the side-effects of some forms of chemotherapy have less
      effect on quality of life than the effects of uncontrolled spread of cancer.
      RESULTS - COSTS: The total cost to the NHS of using these new drugs in England
      and Wales might be about GBP 10 million per annum, but is subject to a number of
      factors. There would be non-financial constraints on any increase in chemotherapy
      for the next few years, such as staffing; the number of patients choosing to have
      the newer forms of chemotherapy is not yet known; and the costs of the drugs may
      fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED:
      The available data did not provide an entirely satisfactory basis for cost
      effectiveness calculations. The main problem was the lack of direct comparisons
      of the new drugs. In order to strengthen the analysis, three different modelling
      approaches were used: pairwise comparisons using trial data; cost-minimisation
      analysis, as if all the new regimens were of equal efficacy; and cost
      effectiveness analysis pooling the results of several trials with different
      comparators, giving indirect comparisons of the new drugs by using BSC as the
      common comparator. A number of different scenarios were explored through
      extensive sensitivity analysis in each model. Outcomes were expressed in
      incremental cost per life-year saved or incremental cost, versus BSC. There was
      insufficient evidence from which to derive cost per quality-adjusted life-year.
      In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel
      plus cisplatin combinations generally performed well against BSC under a range of
      different scenarios and especially when given as a maximum of 3 cycles.
      Incremental cost per life-year gained (LYG) versus BSC varied depending on
      scenario, but baseline figures based on trial data and protocols were: single
      agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206;
      single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041;
      and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel
      gave a cost per LYG of pound 17,546, again well within the range usually accepted
      as cost-effective. However, in routine care, the impact of therapy would be
      regularly reviewed, and continuation would depend on response, side-effects,
      patient choice and clinical judgement. Chemotherapy would be stopped in non
      responders, making chemotherapy more cost-effective. A 'real-life' scenario in
      which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives
      much lower costs per LYG, with single-agent gemcitabine, single-agent
      vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared
      with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478
      per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains
      in duration of survival were achieved without diminution of quality of life (at
      best, they improved quality) and with relatively low incremental cost.
      Comparisons among the individual drugs should be viewed with caution because they
      have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE
      ANALYSIS: Each of the three models had limitations. The cost-effectiveness
      estimates from the pairwise comparisons were based on single studies. The cost
      minimisation analysis assumed that the regimens have equal efficacy in practice.
      The cost-effectiveness analysis had to be based on pooling data from individual
      trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish
      data. Median rather than mean data on duration of survival have been used in the
      analysis, because most of the trials reported only median data. Median survival
      and number of drug cycles were calculated by averaging across a number of
      studies, rather than being reliant on one particular study. The costs of the less
      expensive antiemetics cited in the trials were omitted. The use of more modern
      and costly antiemetics would have a modest detrimental effect on cost
      effectiveness. In the absence of published data, an estimate was made of the cost
      of side-effects of chemotherapy, in particular hospital admissions, and applied
      to all the new regimens. In practice, admissions related to side-effects and
      their respective costs are likely to vary by regimen. CONCLUSIONS: The new drugs
      for non-small-cell lung cancer extend life by only a few months compared with
      BSC, but appear to do so without net loss in quality of life and at a cost per
      LYG that is much lower than for many other NHS activities. Depending on
      assumptions used, these new drugs range from being cost-effective, as
      conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE
      NEWER DRUGS: One of the present constraints on chemotherapy is availability of
      inpatient beds. The advent of newer and gentler forms of chemotherapy given on an
      outpatient basis would not only overcome this, but it would allow more patients
      to be treated. This might apply particularly to older patients. The treatment of
      more patients would increase workload for oncologists, cancer nurses and
      pharmacists. The Government has already announced increased expenditure on staff
      for cancer care. The previously pessimistic attitudes to chemotherapy in non
      small-cell lung cancer are changing in the wake of the newer agents, and this
      shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH:
      Recent advances in chemotherapy are welcome, but their effects remain small for
      patients with non-small-cell lung cancer. Much more research is needed into
      better drugs, better combinations, new ways of assessing the likelihood of
      response and especially direct comparisons between the new regimens. This
      research would be aided by having a greater proportion of patients involved in
      trials, but there will be infrastructure implications of increased participation.

PMID- 12065069
TI  - The cardioprotection of calcitonin gene-related peptide-mediated preconditioning.
AB  - Preconditioning induced by brief ischemia or hyperthermia or some drugs shows two
      phases, early and delayed protection. The cardioprotection afforded by
      preconditioning is related to stimulation of endogenous mediators release.
      Calcitonin gene-related peptide (CGRP), a major transmitter of capsaicin
      sensitive sensory nerves, has recently been shown to play an important role in
      mediation of the preconditioning induced by brief ischemia or hyperthermia or by
      some drugs, and alpha-CGRP seems to play a major role in the mediation of delayed
      preconditioning. It has been shown that the cardioprotection afforded by CGRP
      mediated preconditioning is due to inhibition of cardiac tumor necrosis factor
      alpha (TNF-alpha) production, but not to the activation of the K(ATP) channel.

PMID- 12065070
TI  - Neurotensin causes tyrosine phosphorylation of focal adhesion kinase in lung
      cancer cells.
AB  - The effects of neurotensin on focal adhesion kinase were investigated using lung
      cancer cells. Neurotensin bound with high affinity to large cell carcinoma cell
      line NCI-H1299 as did neurotensin-(8-13), but not neurotensin-(1-7) or
      levocabastine. Addition of 100 nM neurotensin to NCI-H1299 cells caused transient
      tyrosine phosphorylation of focal adhesion kinase which was maximal after 1-2.5
      min. Also, neurotensin-(8-13), but not neurotensin-(1-8) or levocabastine, caused
      tyrosine phosphorylation of focal adhesion kinase after addition to NCI-H1299
      cells. Focal adhesion kinase tyrosine phosphorylation caused by neurotensin was
      inhibited by the nonpeptide neurotensin receptor antagonist (2-(1-(7
      chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carbonyl)amino)
      adamantane-2-carboxylic acid) (SR48692). SR48692 inhibited the clonal growth of
      NCI-H1299 cells, whereas neurotensin-stimulated proliferation and levocabastine
      had no effect. These results indicate that lung cancer cells have functional
      neurotensin receptors which regulate focal adhesion kinase tyrosine
      phosphorylation. It remains to be determined if neurotensin receptors and focal
      adhesion kinase plays a role in lung cancer cellular adhesion and migration.

PMID- 12065071
TI  - Binding properties of the novel, non-peptide CGRP receptor antagonist
      radioligand, [(3)H]BIBN4096BS.
AB  - BIBN4096BS [[R-(R,(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1
      piperazinyl]carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2
      oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-Piperidinecarboxamide] is a
      selective calcitonin gene-related peptide (CGRP) receptor antagonist with a
      picomolar affinity to the CGRP receptor in human neuroblastoma SK-N-MC cells.
      Here, we describe the characterisation of the binding properties of the tritiated
      radioanalogue of BIBN4096BS in SK-N-MC cells as well as in marmoset tissue.
      [(3)H]BIBN4096BS showed reversible and saturable binding to SK-N-MC cells with a
      K(D) of 0.045 nM. In competition experiments, [3(H)]BIBN4096BS is concentration
      dependently displaced from SK-N-MC cell membranes by BIBN4096BS as well as by the
      endogenous ligand CGRP and its analogues with the rank order of affinity
      BIBN4096BS>human alpha-CGRP=human beta-CGRP>[Cys(Et)(2,7)]human alpha
      CGRP>adrenomedullin (high affinity site)=human alpha-CGRP-(8-37)=human beta-CGRP
      (8-37)>calcitonin=amylin. In the marmoset cortex, saturable [(3)H]BIBN4096BS
      binding was observed with a K(D) of 0.077 nM. CGRP showed biphasic competition of
      [(3)H]BIBN4096BS binding, whilst BIBN4096BS monophasically displaced its
      radioanalogue with a K(i) of 0.099 nM. These data, using [(3)H]BIBN4096BS,
      confirm the high affinity of this novel antagonist for the primate CGRP receptor
      and demonstrate furthermore that this radioligand is a useful tool to study CGRP
      receptor pharmacology.

PMID- 12065072
TI  - Interleukin-1 inhibits angiotensin II-stimulated protein kinase B pathway in
      renal mesangial cells via the inducible nitric oxide synthase.
AB  - Exposure of rat renal mesangial cells to angiotensin II and angiotensin III leads
      to a rapid phosphorylation and activation of the protein kinase B (PKB) pathway.
      The angiotensin II analogs angiotensin-(1-7), angiotensin-(1-6) and angiotensin
      (3-8) were unable to activate PKB. The angiotensin II and III effects are
      mediated by the angiotensin type 1 receptor as documented by the inhibitory
      action of valsartan. Furthermore, angiotensin II-induced activation of PKB
      involves neither a pertussis toxin-sensitive pathway nor the small G proteins of
      the Rho/Rac/cdc42 family, but is completely blocked by inhibitors of the PI 3
      kinase. Moreover, angiotensin II-stimulated PKB activation is inhibited by long
      term pretreatment with interleukin-1 beta, an effect that is reversed by the NO
      synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). Similarly, the nitric
      oxide donor (Z)-1-[2-Aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate
      (Deta-NO) blocks the angiotensin II-induced PKB activation. The NO-mediated
      inhibition of PKB activation in turn is reversed by the phosphatase inhibitor
      calyculin A but not by ocadaic acid, implying the induction of a protein
      phosphatase 1 activity by NO.

PMID- 12065073
TI  - Influence of some beta-adrenoceptor antagonists on the anticonvulsant potency of
      antiepileptic drugs against audiogenic seizures in DBA/2 mice.
AB  - The two enantiomers of propranolol antagonize generalized tonic-clonic seizures
      in DBA/2 mice with the (-)-enantiomer being about 1.5 times more potent than the
      (+)-enantiomer. Metoprolol was less active and atenolol was unable to affect
      audiogenic seizures. In combination with conventional antiepileptic drugs, both
      propranolol enantiomers tested in doses not affecting the occurrence of
      audiogenic seizures increased the anticonvulsant activity of diazepam,
      phenobarbital, valproate and lamotrigine and tended to increase that of
      carbamazepine and phenytoin. The effect was more pronounced with the (-)
      enantiomer. This increase was associated with an enhancement of motor impairment,
      however, the therapeutic index of combined treatment of the antiepileptic drugs
      with both propranolol enantiomers was more favourable than the combination with
      saline alone. Metoprolol was also able to decrease the ED(50) values of the
      antiepileptic drugs, whereas atenolol showed no effects. Since neither enantiomer
      of propranolol significantly influenced the total and free plasma levels of the
      antiepileptics, pharmacokinetic interactions are not likely. In addition, (+)-
      and (-)-propranolol did not significantly affect the hypothermic effects of the
      antiepileptics tested. In conclusion, both enantiomers of propranolol and
      metoprolol showed an additive anticonvulsant effect when co-administered with
      some conventional antiepileptic drugs, most notably diazepam, phenobarbital,
      lamotrigine and valproate, implicating a possible therapeutic relevance of such
      drug combinations.

PMID- 12065074
TI  - Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter.
AB  - Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4
      diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine
      transporter at low micromolar concentration. DIFEQ is a neutral derivative of the
      chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-,
      and feruloyl-esters of quinic acid, formed in the roasting process of coffee.
      Displacement of the adenosine transporter antagonist [(3)H](S)-(nitrobenzyl)-6
      thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the
      human adenosine transporter protein (hENT1), showed a K(i) of 0.96+/-0.13 microM.
      Extracts of regular and decaffeinated coffee showed binding activities equivalent
      to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose
      of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in
      correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4
      dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in
      roasted coffee, showed similar affinities for the adenosine transporter, while
      the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two
      orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides
      in coffee could have the potential to raise extra-cellular adenosine levels,
      thereby counteracting the stimulant effect of caffeine.

PMID- 12065075
TI  - In vivo tonic modulation of the noradrenaline release in the rat cortex by locus
      coeruleus somatodendritic alpha(2)-adrenoceptors.
AB  - The regulation of noradrenaline release in the rat cingulate cortex by
      somatodendritic alpha(2)-adrenoceptors placed in the locus coeruleus was
      evaluated by dual-probe microdialysis. The alpha(2)-adrenoceptor antagonists
      BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidazole),
      RS79948 ((8,12,13)-decahydro-3methoxy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]
      naphthyridine) and RX821002 (2-methoxyidazoxan) administered by reverse dialysis
      into the locus coeruleus increased concentration-dependently (0.01-100 microM)
      noradrenaline release in the cortex (maximal effects 170+/-30%, 543+/-17%, 195+/
      26%, respectively). Administration of the alpha(2)-adrenoceptor antagonist
      idazoxan increased at lower (0.1-10 microM) but decreased at the highest dose
      (100 microM) noradrenaline in the cortex. These data demonstrate that
      somatodendritic alpha(2)-adrenoceptors in the locus coeruleus exert an inhibitory
      tonic modulation on noradrenaline release in noradrenergic terminal areas.

PMID- 12065076
TI  - Gender differences in the behavioral effects of methamphetamine.
AB  - The effects of methamphetamine were tested in male and female rats on two
      different behavioral tasks. Following habituation to a locomotor activity
      chamber, female rats were more sensitive to the locomotor activating effect of
      i.p. methamphetamine (0.1-3.0 mg/kg) than were male rats. A similar effect has
      been observed for other psychomotor stimulants, including cocaine and
      amphetamine. However, males and females did not differ on methamphetamine-induced
      place preference following eight conditioning trials with a wide range of doses
      (0.1-5.6 mg/kg). These results suggest that males and females differ in their
      response to methamphetamine for only some behavioral tasks.

PMID- 12065077
TI  - Effect of opioid and cannabinoid receptor antagonism on orphanin FQ-induced
      hyperphagia in rats.
AB  - Feeding induced in rats by cerebroventricular (i.c.v.) injection of orphanin FQ
      was potently and dose-dependently reversed by peripheral injection of either the
      opioid antagonist naloxone or the cannabinoid CB(1) receptor antagonist SR
      141716[N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophelyl)-4-methyl-3-pyrazole
      carboxamine]. The combination of these two agents inhibited food intake in a
      manner suggestive of additivity or supra-additivity.

PMID- 12065078
TI  - Dietary Mg(2+) supplementation restores impaired vasoactive responses in isolated
      rat aorta induced by chronic ethanol consumption.
AB  - Chronic ethanol consumption contributes to cardiovascular dysfunction possibly
      related to loss of Mg(2+). This study was designed to examine the role of dietary
      Mg(2+) supplementation on chronic ethanol ingestion-induced vascular alteration.
      Rats were fed an ethanol liquid diet supplemented with or without Mg(2+) for 12
      weeks. The force-generating capacity was examined in thoracic aortic rings.
      Ethanol-consuming animals exhibited significantly elevated blood pressure. In
      aorta with intact endothelium, the contractile responses to norepinephrine and
      KCl were greatly attenuated and potentiated, respectively. Interestingly, the
      ethanol-induced alterations in blood pressure and vasoconstrictive response were
      restored by Mg(2+) supplementation. Pretreatment with the beta(1)-adrenoceptor
      antagonist atenolol in intact aortic rings abolished the difference in response
      to norepinephrine between the control and ethanol groups, which implies the
      involvement of a weakened beta(1)-adrenoceptor component in vessels from the
      ethanol-fed rats. The norepinephrine-induced vasoconstriction in intact aorta
      rings was completely abolished by the alpha(1)-adrenoceptor antagonist prazosin.
      In endothelium-denuded aorta, the contractile response to norepinephrine or KCl
      was not significantly different between the ethanol and Mg(2+) groups.
      Endothelium-dependent vasorelaxation to carbamylcholine chloride was not altered
      by either ethanol or Mg(2+) supplementation. Sodium nitroprusside-induced
      vasorelaxation was depressed by ethanol, and restored by Mg(2+), in aorta with or
      without endothelium. These data suggest that chronic ethanol consumption
      contributes to alterations of endothelium-dependent and -independent vascular
      response. These alterations can be compensated by dietary Mg(2+) supplementation.

PMID- 12065079
TI  - Cisplatin up-regulates the adenosine A(1) receptor in the rat kidney.
AB  - Cisplatin, a widely used anticancer drug, produces significant oto- and
      nephrotoxicity. Previous data from our laboratory, using cultured cell lines,
      indicated that cisplatin increases the expression of the adenosine A(1) receptor
      subtype through generation of reactive oxygen species and activation of nuclear
      factor-kappa B (NF-kappa B). Since the adenosine A(1) receptor plays an important
      role in normal renal physiology, this study was performed to determine whether
      cisplatin modulates adenosine A(1) receptor expression in vivo and whether these
      receptors play a role in the nephrotoxicity. Male Sprague-Dawley rats, treated
      with cisplatin (8 mg/kg), developed nephrotoxicity within 3 days, as demonstrated
      by increased serum creatinine and blood urea nitrogen. Cisplatin also produced a
      significant increase in malondialdehyde, apoptosis and necrosis in the kidney.
      The above changes were associated with a time-dependent increase in the
      expression of adenosine A(1) receptor, as determined by radioligand binding
      assays, Western blotting and immunocytochemistry, and an increase in adenosine
      A(1) receptor transcripts. Administration of selective and nonselective
      antagonists of the adenosine A(1) receptor produced either no change or
      exacerbated the nephrotoxicity produced by cisplatin. These data indicate that
      cisplatin can regulate the adenosine A(1) receptor in the kidney and suggest a
      cytoprotective role of this receptor subtype against cisplatin-induced
      nephrotoxicity.

PMID- 12065080
TI  - Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats.
AB  - In preceding papers, we proposed that procainamide hydrochloride, a class I
      antiarrhythmic agent, was able to protect mice and rats from cisplatin-induced
      nephrotoxicity and that it could exert its action through accumulation in kidneys
      followed by coordination with cisplatin (or its hydrolysis metabolites) and
      formation of a less toxic platinum compound similar to the new platinum(II)
      triamine complex cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]
      chlorideplatinum(II) monohydrochloride monohydrate, obtained by the reaction of
      cisplatin with procaine hydrochloride. Hepatotoxicity is not considered as a dose
      limiting toxicity for cisplatin, but liver toxicity can occur when the
      antineoplastic drug is administered at high doses. Here, we report that
      procainamide hydrochloride, at an i.p. dose of 100 mg/kg, reduces cisplatin
      induced hepatotoxicity, as evidenced by the normalization of plasma activity of
      glutamic oxalacetic transaminase and gamma-glutamyl transpeptidase, as well as by
      histological examination of the liver tissue. Twenty-four hours after i.p.
      treatment with the combination of 7.5 mg/kg cisplatin and 100 mg/kg procainamide,
      a significant increase of procainamide (+56%, P<0.05), total platinum (+31%,
      P<0.05), platinum-DNA adducts (+31%, P<0.05) and percent DNA-DNA interstrand
      cross-links (+69%, P<0.02) was found in liver tissue, as compared to animals
      treated with cisplatin alone. Moreover, in accordance with these findings, we
      also observed a slightly lower concentration and cumulative excretion of platinum
      in the feces. Since mitochondrial injury is considered a central event in the
      early stages of the nephrotoxic effect of cisplatin, the distribution of platinum
      in these subcellular organelles obtained from hepatocytes was determined after
      treatment with cisplatin with or without procainamide hydrochloride, together
      with platinum concentration in their cytosolic fraction. Our data show that the
      coadministration of procainamide hydrochloride produced a rearrangement of
      subcellular platinum distribution in hepatocytes with a slight decrease in
      mitochondria (-15%, P<0.10) and a slight increase in the cytosolic fraction
      (+40%, P<0.10) of platinum content, compared to the treatment with cisplatin
      alone. In analogy with our previous results in the kidney, confirmed here by our
      data in vitro, we suggest that the hepatoprotective activity of procainamide
      hydrochloride is linked to the formation of a less toxic platinum complex, which
      leads to inactivation of cisplatin itself and/or its highly toxic hydrolysis
      metabolites and to a different subcellular distribution of platinum.

PMID- 12065081
TI  - Resiniferatoxin antagonizes cisplatin-induced emesis in dogs and ferrets.
AB  - We evaluated the antiemetic activity of resiniferatoxin, an ultrapotent capsaicin
      analogue, on cisplatin- and apomorphine-induced emesis in dogs, and on cisplatin
      induced acute and delayed emesis in ferrets. In the dog, resiniferatoxin (10
      microg/kg, s.c.) 30 min before the injection of cisplatin markedly prevented
      acute emesis induced by cisplatin. When animals were given resiniferatoxin (10
      microg/kg, s.c.) 24 h prior to cisplatin, the emesis was still inhibited, but not
      significantly. Resiniferatoxin (10 microg/kg, s.c.) 30 min before the
      administration of apomorphine also significantly reduced the emetic responses
      induced by apomorphine in dogs. In the ferret, resiniferatoxin (10 microg/kg,
      s.c.) 30 min prior to cisplatin completely inhibited acute emesis caused by
      cisplatin (10 mg/kg, i.p.). When ferrets were given resiniferatoxin (10
      microg/kg, s.c.) 16 h prior to cisplatin, the emesis was still significantly
      inhibited. Cisplatin (5 mg/kg, i.p.) induced both acute (0-24 h) and delayed (24
      72 h) phase emesis, and a single injection of resiniferatoxin (10 microg/kg,
      s.c.) at 36 h after cisplatin significantly reduced subsequent emetic responses
      during the 36-72 h period. These results suggest that resiniferatoxin-related
      vanilloids may be useful drugs against both acute and delayed emesis induced by
      cancer chemotherapy.

PMID- 12065082
TI  - O-Substituted derivatives of pralidoxime: muscarinic properties and protection
      against soman effects in rats.
AB  - O-Substituted aldoximes of the cholinesterase reactivator pralidoxime (O-methyl
      1, O-benzyl 2, O-propynyl 3 and O-butynyl 4 derivatives) were synthesized and
      found to exhibit strong binding affinities for muscarinic receptors in rat brain,
      heart and submandibulary glands. The aldoximes were noncompetitive antagonists of
      acetylcholine-induced contraction of the guinea pig ileum. A good correlation was
      observed between binding affinity and pK(B). Weak anticholinesterase activities
      were observed for these compounds. When given intracerebroventricularly into
      conscious rats before soman administration (0.9 LD(50), subcutaneously), the
      aldoximes, like atropine but not pralidoxime, protected against respiratory
      depression (3,4) and bradycardia (2). No protection against soman-induced pressor
      effects was noted. The protective effects of these aldoximes may be the outcome
      of compensatory mechanisms, of which the cholinergic receptor agonist and
      antagonist properties of these compounds may be important.

PMID- 12065083
TI  - Differential responsiveness of proximal and distal parts of isolated guinea pig
      trachea.
AB  - This study addressed the question whether proximal and distal guinea pig tracheal
      segments respond differently to contractile agents. Using a perfused trachea set
      up, histamine, KCl or the cyclo-oxygenase inhibitor, indomethacin, could be
      administered selectively to the mucosa (at the inside) or the serosa (at the
      outside) of the tracheal segments. Proximal parts contracted significantly more
      (40-60%) than distal parts when 1 mM histamine was administered to the mucosal or
      serosal side or when KCl (50 mM) was added to the serosal side. When histamine
      was administered to the mucosal side of epithelium-denuded segments, the
      contractions were twice as high in proximal than in distal parts (3057 vs. 1526
      mg). Inhibition of tracheal cyclo-oxygenase with indomethacin at the mucosal side
      increased proximal and distal reactivity to mucosally administered histamine to
      the same extent. Serosal administration of indomethacin, however, increased
      histamine reactivity only in proximal segments (from 2690 to 5180 mg). In the
      latter segments, subsequent administration of histamine to the serosal side
      further increased the contraction, while serosal histamine in the absence of
      serosal indomethacin produced a relaxation (net difference of 4672 mg). In
      conclusion, the higher intrinsic contractility of proximal tracheal segments is
      counteracted by serosal cyclo-oxygenase products.

PMID- 12065084
TI  - A possible effect of sulfhydryl reagents on the contractile activity of the rat
      detrusor muscle.
AB  - We aimed to investigate the effect of sulfhydryl (SH) inactivating agents,
      ethacrynic acid and N-ethylmaleimide, on the contractile activity of rat detrusor
      muscle. Wistar Kyoto rats weighing 150-250 g were anaesthetized with ketamine and
      bled to death. The urinary bladders were surgically removed and detrusor strips
      were mounted under 0.5 g tension in organ baths. The responses were recorded with
      isotonic transducers on polygraph paper. After an equilibrium period, the tissues
      were contracted by electrical field stimulation, acetylcholine, ethacrynic acid
      or N-ethylmaleimide and the effects of L-cysteine, glutathione, verapamil, Ca(2+)
      free solution, sodium nitroprusside or atropine were then examined on these
      contractions. Verapamil, Ca(2+)-free solution or atropine significantly reduced
      the contractions elicited by electrical field stimulation and acetylcholine
      whereas L-cysteine, glutathione or sodium nitroprusside had no effect on the
      contractions in response to these stimuli. L-Cysteine, glutathione, verapamil or
      Ca(2+)-free solution significantly inhibited the contractions induced by
      ethacrynic acid or N-ethylmaleimide. Sodium nitroprusside slightly inhibited only
      the contraction induced by ethacrynic acid but not that with N-ethylmaleimide.
      Atropine has no action on the contractions in response to these SH reagents.
      These findings suggest that SH reagents may play a role in the contractile
      activity of rat detrusor muscle and this action seems to be related to the gating
      of Ca(2+) channels. Further experiments are needed to determine the cellular
      mechanism(s) of action by which these SH reagents act on the detrusor smooth
      muscle.

PMID- 12065085
TI  - Iron augments stage-I and stage-II tumor promotion in murine skin.
AB  - Free radical generating organic peroxides and hydroperoxides are known to promote
      tumors in mouse skin and iron has been shown to participate in free radical
      generating reactions. In the present study, we have used various peroxides and
      hydroperoxides as stage-I and -II tumor promoters and have studied the effect of
      iron-overload on the two stages of tumor promotion. Swiss albino mice were iron
      overloaded by injecting iron-dextran (1.0 mg Fe/mouse per day for 15 days).
      Twenty-four hours after the last injection of iron-dextran, the animals were
      initiated with 40 microg 7,12 dimethylbenz[a]anthracene. One week following
      initiation stage-I tumor promotion was accomplished by applying 12-O
      tetradecanoyl phorbol-13-acetate (TPA), benzoyl peroxide (BPO), cumene
      hydroperoxide (COOH) or H(2)O(2) to mice twice weekly for 2 weeks. Stage-II tumor
      promotion was accomplished by applying mezerein, BPO, COOH or H(2)O(2) to these
      mice twice weekly for 40 weeks. The appearance of the first papilloma and the
      number of tumors/mouse were recorded weekly. When compared to non-iron-overloaded
      mice, the iron-overloaded mice showed a higher tumor incidence and number of
      tumors/mouse. The order in which iron-overload was effective in increasing tumor
      promotion by stage-I tumor promoters was H(2)O(2)>COOH>BPO>TPA and the order in
      which iron-overload was effective in increasing tumor promotion by stage-II tumor
      promoters was COOH>mezerein>BPO. Induction in ornithine decarboxylase (ODC)
      activity, [(3)H]thymidine incorporation in cutaneous DNA and cutaneous lipid
      peroxidation were also higher in the iron-overloaded mice. TPA was the most
      effective in inducing epidermal ODC activity and [(3)H]thymidine incorporation
      followed by mezerein, COOH and BPO. In addition, the level of epidermal reduced
      glutathione and the activities of antioxidant enzymes were lower in iron
      overloaded mice. Besides this, cutaneous iron levels were higher in iron
      overloaded mice. Thus, we conclude from this study that iron-overload augments
      stage-I and stage-II of tumor promotion in murine skin.

PMID- 12065086
TI  - P53 codon 72 polymorphism and risk of squamous cell carcinoma of the head and
      neck: a case-control study.
AB  - p53 plays an important role in cell-cycle control, as it facilitates DNA repair
      activities in response to DNA damage. An aberrant cell cycle impairs DNA repair
      and increases the probability of mutations that lead to carcinogenesis. The p53
      codon 72 Arg/Pro polymorphism has been suggested to be associated with
      susceptibility to tobacco-related cancers, but this association remains
      controversial. In this hospital-based case-control study of 304 patients newly
      diagnosed with squamous cell carcinoma of the head and neck (SCCHN) and 333
      cancer-free controls, we evaluated the association between this p53 polymorphism
      and the risk of SCCHN. All subjects were non-Hispanic whites, and the controls
      were frequency-matched to the cases by age (+/-5 years), sex and smoking status.
      Our results suggested that there was no difference in the distributions of p53
      codon 72 genotypes between cases and controls (odds ratio (OR)=1.04, 95%
      confidence interval (CI) 0.75-1.44 for Pro/Pro vs. Arg/Arg and OR=1.01, 95% CI
      0.54-1.91 for Arg/Pro vs. Arg/Arg). However, there was evidence that the Pro
      allele was associated with an early age of onset of SCCHN. The median ages of
      onset of SCCHN were 59, 56 and 53 years for Arg/Arg, Arg/Pro and Pro/Pro cases,
      respectively (P=0.151 among three genotypes; P=0.057 for Pro/Pro and Arg/Pro
      combined vs. Arg/Arg). The median ages at onset of oral cancers were 62, 57 and
      51 years for Arg/Arg, Arg/Pro and Pro/Pro, respectively (P=0.091 among three
      genotypes; P=0.046 for Pro/Pro vs. Arg/Arg; P=0.066 for Pro/Pro and Arg/Pro
      combined vs. Arg/Arg). While the results suggest that the P53 codon 72
      polymorphism may contribute to oral cancer susceptibility, larger studies are
      needed to confirm these findings.

PMID- 12065087
TI  - A bitter diterpenoid furanolactone columbin from Calumbae Radix inhibits
      azoxymethane-induced rat colon carcinogenesis.
AB  - The modifying effect of dietary administration of a diterpenoid furanolactone
      columbin isolated from the crude drug Calumbae Radix (the root of Jateorhiza
      columba MIERS, Menispermacea) on azoxymethane (AOM)-induced was investigated in
      male F344 rats. Animals were initiated with AOM (three weekly subcutaneous
      injections of 15 mg/kg body weight) to induce colonic neoplasms. They were fed
      the experimental diets mixed with columbin (4, 20, and 100 ppm) for 4 weeks,
      starting 1 week before the first dosing of AOM and thereafter maintained on the
      basal diet without columbin. Additional experimental groups included the AOM
      alone group, the columbin alone group (100 ppm in diet for 4 weeks), and the
      untreated control group. Dietary feeding of columbin (4, 20, and 100 ppm) during
      the initiation phase of AOM-induced colon carcinogenesis reduced the incidence
      and multiplicity of colonic adenocarcinoma and the inhibition by feeding of 20
      ppm (incidence: 20%, P=0.0242 and multiplicity: 0.20+/-0.40, P<0.02) and 100 ppm
      (incidence: 10%, P=0.0029 and multiplicity: 0.10+/-0.30, P<0.002) columbin was
      significant when compared with the AOM alone group (incidence: 55% and
      multiplicity: 0.55+/-0.50). Also, columbin administration in diet lowered the
      number of argyrophilic nucleolar organizer regions protein per nucleus in non
      lesional colonic crypts and the blood polyamine content, which are reflected in
      cell proliferation activity. These results indicate chemopreventive ability of
      dietary columbin against chemically induced colon tumorigenesis when fed during
      the initiation phase, providing a scientific basis for chemopreventive ability of
      columbin against human colon cancer.

PMID- 12065088
TI  - Development of tobacco smoke-induced lung tumors in mice fed Bowman-Birk protease
      inhibitor concentrate (BBIC).
AB  - Male strain A/J mice were exposed, 6h a day, 5 days a week for 5 months to a
      mixture of 89% cigarette sidestream and 11% cigarette mainstream smoke and then
      allowed to recover for another 4 months in air. The animals were fed Bowman-Birk
      protease inhibitor concentrate (BBIC) at a concentration of 1% in AIN-93G diet
      either during smoke exposure, following smoke exposure or during the entire 9
      months. At the end of the experiment, the incidence and multiplicity of lung
      tumors were determined. In a positive control experiment, strain A/J mice were
      injected with 3-methylcholanthrene (MCA) and fed a diet containing 1% BBIC; these
      animals were killed 5 months later. It was found that in the animals treated with
      MCA, BBIC decreased lung tumor multiplicities, whereas in the smoke exposed mice,
      BBIC did not modulate lung tumor development.

PMID- 12065089
TI  - Inhibition by arsenic trioxide of human hepatoma cell growth.
AB  - Arsenic trioxide (As(2)O(3)) has been shown to be effective for treatment of
      patients with refractory or relapsed acute promyelocytic leukemia and a variety
      of other malignant hematopoetic disorders. We studied the effect of this agent on
      proliferation of human hepatoma-derived cell lines (SK-Hep-1, HepG2, and HuH7).
      In HuH7 cells, As(2)O(3) reduced proliferation time- and dose-dependently at 1
      and 2 microM, while in SK-Hep-1 and HepG2 cells, As(2)O(3) inhibited
      proliferation at 2 and 4 microM respectively. Cell cycle analysis by flow
      cytometry showed that As(2)O(3) induced apoptosis in these hepatoma-derived cells
      as confirmed by appearance of sub-G(1) cells. Sensitivity of hepatoma-derived
      cells to As(2)O(3) was inversely related to their intracellular glutathione (GSH)
      and intensity of GSH synthesis. Arsenic sensitivity was restored to relatively
      resistant cell lines when GSH was depleted by L-buthionine sulfoximine (BSO).
      These results indicate that As(2)O(3) may have therapeutic potential for
      treatment of hepatocellular carcinoma.

PMID- 12065090
TI  - Recombinant arginine deiminase as a potential anti-angiogenic agent.
AB  - Arginine deiminase (ADI), isolated from Mycoplasma cell extracts, has been
      suggested to inhibit endothelial cell growth in vitro. However, anti-angiogenic
      activity by ADI has not yet been demonstrated. In this study, we investigated the
      in vitro effect of recombinant ADI (rADI) on the growth, migration, and tube
      formation of human umbilical vein endothelial (HUVE) cells. Mycoplasma arginine
      deiminase was cloned by PCR and the rADI was expressed in Escherichia coli. and
      purified to near homogeneity. The purified recombinant protein was found to have
      characteristics similar to those of the native enzyme: molecular weight (48 kDa)
      and specific enzymatic activity of converting L-arginine into citrulline (32.7
      U/mg). This recombinant enzyme also exhibited an inhibitory effect on the growth
      of HUVE cells. The anti-angiogenic activity was demonstrated by in vitro
      inhibition of migration into the scratch wounded area in HUVE cell monolayers and
      the inhibition of microvessel tube-like formation of HUVE cells on Matrigel
      coated surfaces. These results suggest that arginine deiminase is a potential
      inhibitor for angiogenesis, and that arginine concentrations may play an
      important role in regulating neovascularization.

PMID- 12065091
TI  - Inhibition of cell cycle progression in human leukemia HL-60 cells by esculetin.
AB  - Esculetin, a coumarin compound, was found to inhibit cell growth and cell cycle
      progression by inducing arrest of the G1 phase in HL-60 cells. To obtain
      information regarding cell cycle arrest induced by esculetin, we examined its
      effect on the regulating factors of the G1 phase in the leukemia HL-60 cells
      treated with esculetin by Western blotting. Our observations were: (1) a distinct
      increase in the level of hypophosphorylated retinoblastoma protein (pRb), and a
      reduction in the level of CDK4 after treatment with 100 microM of esculetin for
      24 h; (2) a marked up-regulation of p27, and a down-regulation of cyclin D1 after
      treatment with 100 microM esculetin for 24 h. These results suggest that
      esculetin can inhibit the growth of human leukemia HL-60 cells by G1 phase cell
      cycle arrest as a result of inhibited pRb phosphorylation.

PMID- 12065092
TI  - Regulation of Bcl-2 family molecules and activation of caspase cascade involved
      in gypenosides-induced apoptosis in human hepatoma cells.
AB  - Herbal medicines are increasingly being utilized to treat a wide variety of
      disease processes. Gypenosides (Gyp) are triterpenoid saponins contained in an
      extract from Gynostemma pentaphyllum Makino and reported to induce apoptosis in
      human hepatoma cells. However, the molecular mechanism underlying the Gyp-induced
      apoptotic process is unclear. In this study, we found that Gyp induced apoptosis
      in human hepatoma Huh-7, Hep3B and HA22T cell lines as evidenced by morphological
      changes, 4',6'-diamidino-2-phenylindole staining and in situ terminal transferase
      mediated dUTP-fluorescensin nick end-labeling assay. Our data demonstrated that
      Gyp-induced apoptotic cell death was accompanied by up-regulation of Bax, Bak and
      Bcl-X(L), and down-regulation of Bcl-2 and Bad, while it had no effect on the
      level of Bag-1 protein. Moreover, Gyp treatment caused the release of
      mitochondrial cytochrome c to cytosol and sequential activation of caspases,
      including caspase-1, -9 and -3, then leading to cleavage of poly-ADP-ribose
      polymerase. Furthermore, the Gyp-induced apoptosis was markedly blocked by the
      broad-spectrum caspase inhibitor, z-VAD-fmk. Taken together, these results
      suggest that treatment of human hepatoma cells with Gyp induced apoptosis through
      the up-regulation of Bax and Bak, and down-regulation of Bcl-2, release of
      mitochondrial cytochrome c and activation of caspase cascade.

PMID- 12065093
TI  - Absence of mutations in the transforming growth factor-beta inducible early gene
      1, TIEG1, in pancreatic cancer.
AB  - Pancreatic cancers frequently have defects in components of the transforming
      growth factor-beta (TGF-beta) signaling pathway. TIEG1 (TGF-beta inducible early
      gene) is a recently characterized transcription factor regulated by TGF-beta that
      induces apoptosis when overexpressed in pancreatic adenocarcinoma cell lines.
      Alterations on chromosome 8q, where TIEG1 is located, are also relatively
      frequent in pancreatic cancers. To determine if TIEG1 may be involved in the
      tumorigenesis of pancreatic cancer, we performed mutational screening of this
      gene in 22 pancreatic cancer cell lines. No sequence alterations were observed.
      Reverse transcription-polymerase chain reaction analysis was also performed to
      rule out the possibility that the expression of the gene is altered by genetic
      events other than mutation. Likewise, no alterations in expression were found.
      Thus, an essential role of TIEG1 in pancreatic cancer can be excluded.

PMID- 12065094
TI  - Ca(2+)/calmodulin-dependent protein kinase IV expression in epithelial ovarian
      cancer.
AB  - Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional
      protein kinase expressed abundantly in the central nervous system. Because
      changes in intracellular Ca(2+) concentrations affect progression through the
      mitotic cell cycle, enhanced expression of CaMKIV has been reported in small cell
      lung carcinoma and hepatocellular carcinoma. To elucidate the involvement of
      CaMKIV in epithelial ovarian carcinogenesis, we analyzed serial frozen sections
      for CaMKIV protein expression in 26 patients with ovarian epithelial carcinoma
      and ten patients with benign cystadenoma of the ovary by fluorescent
      immunohistochemistry. We analyzed the relationship between the percentages of
      CaMKIV-stained cells and the patient's characteristics, including histological
      classification, clinical stage, histological grade, and clinical outcome. In the
      benign ovarian cystadenoma, CaMKIV was detected in none of the cases examined.
      Most of the CaMKIV proteins were found in the nucleus of epithelial ovarian
      cancer tissue. CaMKIV expression was significantly associated with clinical stage
      (P<0.01), histological grade (P<0.01), and clinical outcome (P<0.01). Survival
      data were available for all patients, and univariate Cox regression analysis
      showed that CaMKIV expression was significantly associated with poor prognosis
      (P<0.05). Our results demonstrate that CaMKIV expression in epithelial ovarian
      cancer correlates with the malignant potential of this tumor.

PMID- 12065095
TI  - Quantitative detection of CEA expressing free tumor cells in the peripheral blood
      of colorectal cancer patients during surgery with real-time RT-PCR on a
      LightCycler.
AB  - We applied novel real-time reverse transcriptase-polymerase chain reaction (RT
      PCR) with a LightCycler for quantitative detection of carcinoembryonic antigen
      (CEA) mRNA expressing tumor cells in the peripheral blood of colorectal cancer
      patients. Analysis of peripheral blood samples from 99 potentially curative
      colorectal cancer patients revealed a significantly higher mean CEA mRNA value in
      post-operative bloods (18.71) than in pre-operative blood (1.03) (P=0.003).
      Kaplan-Meier analysis demonstrated disease free survival of patients with
      positive CEA mRNA in post-operative blood to be significantly shorter than in
      cases negative for CEA mRNA (P=0.03). These results suggest that tumor cells
      could be shed into the bloodstream during surgical procedures, and these free
      tumor cells are accompanied by a poor patient outcome. Real-time quantitative RT
      PCR is a useful technique for quantitative assessment of free tumor cells in the
      peripheral blood of colorectal cancer patients.

PMID- 12065096
TI  - Tropomyosin-1, a novel suppressor of cellular transformation is downregulated by
      promoter methylation in cancer cells.
AB  - Tropomyosins (TMs) are a family of microfilament binding proteins, which are
      suppressed in the transformed cells. We have investigated the mechanism of
      suppression of TMs, in particular that of tropomyosin-1 (TM1), in breast cancer
      cells. Inhibition of DNA methyl transferase with 5-aza-2'-deoxycytidine (AZA)
      alone did not induce TM1 expression. However, combined treatment of trichostatin
      A (TSA) and AZA resulted in readily detectable expression of TM1, but not that of
      other TM isoforms. Upregulation of TM1 expression paralleled with the reemergence
      of TM1 containing microfilaments, and in abolition of anchorage-independent
      growth. The synergistic action of AZA and TSA in reactivation of TM1 gene was
      also evident in ras-transformed fibroblasts. These data, for the first time, show
      that hypermethylation of TM1 gene and chromatin remodeling are the predominant
      mechanisms by which TM1 expression is downregulated in breast cancer cells.

PMID- 12065097
TI  - Increased expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP) in
      pancreatic tissue from smokers and pancreatic tumor cells.
AB  - Pancreatic cancer is a major cause of deaths in the United States, and has one of
      the lowest 5-year survival rates. Early diagnosis has not been possible due to
      the lack of reliable early tumor markers. The heterogeneous nuclear
      ribonucleoprotein A1/B2 (hnRNP) was recently shown to be up-regulated in the
      early stage of lung cancer. This protein plays an important role in biogenesis
      and transport of mRNA. Up-regulation of hnRNP usually precedes morphological
      differentiation and is considered a good biomarker in the early stages of cancer
      development. Because smoking is a high risk factor for pancreatic cancer, this
      study examined the expression of hnRNP in human pancreatic tissues from smokers
      and non-smokers. A two-fold increase in expression of hnRNP was found overall in
      smokers when compared to non-smokers and smokers who quit (P<0.05). The increase
      in expression of hnRNP was higher in female smokers compared to female non
      smokers. High levels of expression was also shown in a limited number of human
      pancreatic adenocarcinomas and two pancreatic tumor cell lines, HPAF-11 and SU
      86.86. HP-8, a normal primary pancreatic cell line, did not express hnRNP. These
      results strongly suggest that up-regulation of hnRNP may be a good candidate for
      early screening for pancreatic cancer because of its activation in pancreatic
      tissue from smokers and activation in pancreatic adenocarcinomas. Over-expression
      of hnRNP has been suggested as evidence that normal transcriptional regulation is
      altered.

PMID- 12065098
TI  - ESTRO Breur Gold Medal Award Lecture 2001: irradiation accidents-- lessons for
      oncology?
AB  - Considering the number of radioactive sources in use all over the world (both in
      industry and medicine) irradiation accidents are exceedingly rare, as
      demonstrated by the main databases registering such cases: UNSCEAR, IAEA, REAC/TS
      (Oak Ridge, USA), the German group in Ulm and the Paris Institut Curie. The
      precise causes of most accidents have been openly analyzed, allowing to reduce
      the risk of subsequent identical accidental exposures. In addition, a rapid
      retrospective overview shows that positive lessons could be drawn from such
      accidents: 1)Lessons for patient management: one should keep in mind that the
      first ever allogeneic bone marrow transplantations were performed in 1958, on
      scientists from Yugoslavia who had been severely irradiated in a nuclear Research
      laboratory. Apart from what was learned from such accidents for the management of
      severe aplasia, the treatment of superficial accidental exposures has also
      benefited radiotherapy patients in certain specific situations. 2) Lessons for
      technology: the efforts to improve safety in nuclear plants are well known; the
      (successful) efforts to reduce the once-elevated risks when changing the
      therapeutic Cobalt 60 sources are less well known. Today, most irradiation
      accidents (by far) are related to misuse or loss of radioactive sources from
      industrial radiography sets. However, here again, various technological
      improvements significantly reduced the risks. 3) Lessons for radiobiology: the
      need for more and more sophisticated biological dosimetry has led to studies
      allowing better understanding of the short- and long-term effects of radiation on
      human cells. Analyses of samples taken in areas which were heavily accidentally
      irradiated also helped to identify, in particular, the cardinal role of TGF beta
      and TNF alpha in the development of fibrosis and necrosis after irradiation. 4)
      Lessons for prevention of accidents in radiotherapy: only three large-scale
      accidents involving external radiotherapy have been registered in the last
      decade, but deciphering the cause(s) of such problems clearly participated in the
      setting of demanding Quality Assurance programmes and strict national and
      international recommendations. Such open circulation of the information about
      these (fortunately rare) accidents appears to be one of the ways to improve
      Quality Assurance in Radiotherapy.

PMID- 12065099
TI  - Risk group dependence of dose-response for biopsy outcome after three-dimensional
      conformal radiation therapy of prostate cancer.
AB  - BACKGROUND AND PURPOSE: We fit phenomenological tumor control probability (TCP)
      models to biopsy outcome after three-dimensional conformal radiation therapy (3D
      CRT) of prostate cancer patients to quantify the local dose-response of prostate
      cancer. MATERIALS AND METHODS: We analyzed the outcome after photon beam 3D-CRT
      of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan
      Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81Gy)
      who had a prostate biopsy performed >or=2.5 years after end of treatment. A
      univariate logistic regression model based on D(mean) (mean dose in the planning
      target volume of each patient) was fit to the whole data set and separately to
      subgroups characterized by low and high values of tumor-related prognostic
      factors T-stage (<T2c vs. >or=T2c), Gleason score (<or=6 vs. >6), and pre
      treatment prostate-specific antigen (PSA) (<or=10 ng/ml vs. >10 ng/ml). In
      addition, we evaluated five different classifications of the patients into three
      risk groups, based on all possible combinations of two or three prognostic
      factors, and fit bivariate logistic regression models with D(mean) and the risk
      group category to all patients. Dose-response curves were characterized by
      TCD(50), the dose to control 50% of the tumors, and gamma(50), the normalized
      slope of the dose-response curve at TCD(50). RESULTS: D(mean) correlates
      significantly with biopsy outcome in all patient subgroups and larger values of
      TCD(50) are observed for patients with unfavorable compared to favorable
      prognostic factors. For example, TCD(50) for high T-stage patients is 7Gy higher
      than for low T-stage patients. For all evaluated risk group definitions, D(mean)
      and the risk group category are independent predictors of biopsy outcome in
      bivariate analysis. The fit values of TCD(50) show a clear separation of 9-10.6Gy
      between low and high risk patients. The corresponding dose-response curves are
      steeper (gamma(50)=3.4-5.2) than those obtained when all patients are analyzed
      together (gamma(50)=2.9). CONCLUSIONS: Dose-response of prostate cancer,
      quantified by TCD(50) and gamma(50), varies by prognostic subgroup. Our
      observations are consistent with the hypothesis that the shallow nature of
      clinically observed dose-response curves for local control result from a patient
      population that is a heterogeneous mixture of sub-populations with steeper dose
      response curves and varying values of TCD(50). Such results may eventually help
      to identify patients, based on their individual pre-treatment prognostic factors,
      that would benefit most from dose-escalation, and to guide dose prescription.

PMID- 12065100
TI  - Considerations on treatment efficiency of different conformal radiation therapy
      techniques for prostate cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate the treatment efficiency of different
      conformal radiation therapy techniques in prostate cancer. MATERIALS AND METHODS:
      Three major classes of intensity-modulated radiation therapy (IMRT) delivery as
      well as a conformal rotation technique have been evaluated: sequential
      tomotherapy, dynamic multileaf collimation (DMLC) with conventional MLC, DMLC
      with miniMLC and dynamic field shaping arc. Treatment planning for the IMRT
      techniques has been performed with inverse planning. Forward planning was used
      for the dynamic arc technique. The four techniques have been compared to treat
      two different prostate cases with a conservative target dose of 70 Gy: a convex
      shaped target volume and one containing concavities formed by the bladder and
      rectum. Cumulative dose volume histograms, tumor control probability and normal
      tissue complication probability, conformity index and dose heterogeneity, and
      finally efficiency of treatment delivery have been evaluated. RESULTS: For the
      convex shaped target, all treatment modalities met the desired treatment goals,
      although the conventional MLC delivered more dose to the bladder. Compared to the
      dynamic arc modality, both tomotherapy and the conventional MLC technique needed
      a tenfold higher number of monitor units per target dose, and the miniMLC a
      twofold higher number. The same trend has been observed for the concave target,
      yet the dynamic arc did not meet the desired dose reduction for the rectum. The
      miniMLC configuration represented the best compromise for both targets with
      respect to treatment goals and delivery efficiency. Sequential tomotherapy
      performed adequately with respect to conformity at the cost of efficiency.
      CONCLUSIONS: Together with conformity and delivery efficiency the shape of the
      target should be considered as an important parameter in the selection of the
      treatment modality.

PMID- 12065101
TI  - Computed tomography determination of prostate volume and maximum dimensions: a
      study of interobserver variability.
AB  - OBJECTIVE: (1) To evaluate the reproducibility of prostate volume, maximum
      dimensions and geometrical center coordinates determination using computed
      tomography (CT) and (2) to identify patterns of interobserver variability.
      MATERIALS AND METHODS: Forty patients, suitable for our brachytherapy program,
      were selected for the study. All patients underwent CT scanning and the prostate
      volumes were determined by three radiation oncologists. Measurements of
      geometrical center coordinates, maximum organ dimensions in the anterior
      posterior (AP), lateral (Lat) and longitudinal (Long) axes as well as prostate
      volumes were recorded. This yielded 840 measurements of seven variables for
      analysis. The means and corresponding standard deviations (SD) of each variable
      were calculated for each patient. The SDs were then averaged and presented as
      indices of dispersion. Average variations from the mean were also calculated for
      each observer along with the SDs. RESULTS: Analysis of the geometrical center
      coordinates revealed acceptable variability amongst observers. For the AP, Lat
      and Long coordinates the SDs were 0.78, 0.89 and 1.72 mm, respectively. The
      corresponding values for the maximum organ dimensions were 2.54, 2.72 and 4.43
      mm, respectively. While the volumes outlined by observer B were less than or
      equal to the mean in 95% of cases and those of observer C were greater than or
      equal to the mean in 93% of cases, the volumes of observer A were equally
      distributed above and below the mean (48% in both cases). CONCLUSION: The
      determination of the geometrical center coordinates was reproducible amongst
      observers. The largest variations were seen with the Long axis. The volume
      determination is more variable. However, a characteristic trend was seen amongst
      observers when their volumes were compared to the mean volumes of the group.

PMID- 12065102
TI  - Radiation-induced liver disease after radiotherapy for hepatocellular carcinoma:
      clinical manifestation and dosimetric description.
AB  - Twelve patients with hepatocellular carcinoma and chronic hepatitis developed
      radiation-induced liver disease (RILD) after three-dimensional conformal
      radiotherapy. Six patients died of RILD and six recovered. Mean prescribed dose
      was 50.6+/-4.3Gy, in a daily fraction of 1.8-2.0Gy. Commonly used dosimetric
      parameters, such as fraction volume of normal liver with radiation dose >30Gy,
      prediction score, and normal tissue complication probability, failed to
      differentiate the fatality and clinical types of this complication. Elevated
      transaminases are more frequently seen than ascites and elevated alkaline
      phosphamide are seen in patients with RILD.

PMID- 12065103
TI  - Long-term results (10 years) of intensive breast conserving therapy including a
      high-dose and large-volume interstitial brachytherapy boost (LDR/HDR) for T1/T2
      breast cancer.
AB  - BACKGROUND AND PURPOSE: During the past 15 years many retrospective studies and
      prospective randomized trials have been published supporting the use of breast
      conserving treatment (BCT) including surgery and radiotherapy. However, there are
      still many controversies on the necessary amount of resection, the width of the
      resection margins and the optimal radiation technique, dose and volume, in
      particular of the boost. In this retrospective study a large cohort of 410 women
      with early breast cancer treated with BCT including an interstitial brachytherapy
      (BT) boost is evaluated after a long follow-up period. MATERIAL AND METHODS: In
      order to clarify the impact of the different treatment-related factors on local
      control, these were carefully discriminated, based on widely accepted
      classification and reporting systems for surgery as well as for radiotherapy. The
      surgical approach was classified according to EORTC criteria and a high rate of
      quadrantectomies (60%) was found. Dose and volume of interstitial BT is reported
      according to recommendations of ICRU 58, and reveals a significant radiation dose
      and volume: minimum target dose, mean central dose (MCD) and '85% of MCD' for low
      dose rate (LDR) BT was mean 20, 28 and 24 Gy, for high-dose rate (HDR) BT it was
      mean '10, 15 and 13 Gy, respectively; the treated volume was 104 cc for LDR BT
      and 83 cc for HDR BT. RESULTS: The actuarial rates for overall survival, disease
      free survival and disease-specific survival were 97, 90 and 98% at 5 years and
      85, 79 and 92% at 10 years. There have been only 16 breast recurrences in 410
      treated patients resulting in a 5- and 10-year actuarial local recurrence rate of
      2 and 3.9%, respectively; six recurrences (1.5%) were in the original quadrant.
      Except age and menopausal status, all tumour- and patient-related risk factors
      had no significant impact on local control. CONCLUSIONS: Our data confirm that
      intensive BCT leads to excellent long-term results in terms of local control,
      masking classical risk factors. This high-dose and large-volume interstitial BT
      seems to be superior to classical BCT without BT.

PMID- 12065104
TI  - The effect of overall treatment time on the survival and toxicity of radical
      radiotherapy for cervical carcinoma.
AB  - BACKGROUND AND PURPOSE: Overall treatment time is an important factor in the
      outcome of radical radiotherapy in head and neck, bladder and lung cancer and in
      cervix cancer treated over more than 7 weeks. This study analysed the effect of
      prolongation of overall treatment time on survival and late morbidity for
      patients receiving radical radiotherapy for cervical cancer treated with a 4-week
      regimen. MATERIALS AND METHODS: Using the departmental SAS data-base we
      identified all patients with cervix cancer treated between 1974 and 1988 and
      investigated the 647 patients who received 20 fractions of external beam
      radiotherapy plus intracavitary therapy with a total dose to point A of at least
      60Gy. A retrospective case-note review identified tumour and treatment-related
      variables. RESULTS: Four hundred and twenty-five (66%) patients had at least one
      gap in treatment. Seventy-nine gaps (11%) were due to unavoidable patient or
      treatment-related causes. We could not find an effect of a treatment gap (P=0.43)
      or an increased overall treatment time (P=0.79) on the cause specific survival of
      patients. There was significantly more grade 4 morbidity in those patients
      treated over a short period (29-32 days) compared to the rest (P=0.005), possibly
      related to the loss of radiotherapy-free days to weekend intracavitary
      insertions. CONCLUSIONS: We could not demonstrate a significant effect of overall
      treatment time in this series of patients, almost all of whom were treated in
      less than 7 weeks. Those patients treated over the shortest period had an
      increased incidence of late morbidity.

PMID- 12065105
TI  - High-dose, high-precision treatment options for boosting cancer of the
      nasopharynx.
AB  - PURPOSE: The aim of the study is to define the role and type of high-dose, high
      precision radiation therapy for boosting early staged T1,2a, but in particular
      locally advanced, T2b-4, nasopharyngeal cancer (NPC). MATERIALS AND METHODS:
      Ninety-one patients with primary stage I-IVB NPC, were treated between 1991 and
      2000 with 60-70Gy external beam radiation therapy (ERT) followed by 11-18Gy
      endocavitary brachytherapy (ECBT) boost. In 1996, for stage III-IVB disease,
      cisplatinum (CDDP)-based neoadjuvant chemotherapy (CHT) was introduced per
      protocol. Patients were analyzed for local control and overall survival. For a
      subset of 18 patients, a magnetic resonance imaging (MRI) scan at 46Gy was
      obtained. After matching with pre-treatment computed tomogram, patients
      (response) were graded into four categories; i.e. LD (T1,2a, with limited
      disease, i.e. disease confined to nasopharynx), LRD (T2b, with limited residual
      disease), ERD (T2b, with extensive residual disease), or patients initially
      diagnosed with T3,4 tumors. Dose distributions for ECBT (Plato-BPS v. 13.3,
      Nucletron) were compared to parallel-opposed three-dimensional conformal
      radiation therapy (Cadplan, Varian Dosetek v. 3.1), intensity modulated radiation
      therapy (IMRT) (Helios, Varian) and stereotactic radiotherapy (SRT) (X-plan,
      Radionics v. 2.02). RESULTS: For stage T1,2N0,1 tumors, at 2 years local control
      of 96% and overall survival of 80% were observed. For the poorest subset of
      patients, well/moderate/poorly differentiated T3,4 tumors, local control and
      overall survival at 2 years with CHT were 67 and 67%, respectively, vs. local
      control of 20% and overall survival of 12% without CHT. For LD and LRD, conformal
      target coverage and optimal sparing can be obtained with brachytherapy. For T2b
      ERD and T3,4 tumors, these planning goals are better achieved with SRT and/or
      IMRT. CONCLUSIONS: The dosimetric findings, ease of application of the
      brachytherapy procedure, and the clinical results in early staged NPC,
      necessitates ERT combined with brachytherapy boost to be the therapy of
      preference for LD and LRD. For locally advanced T3,4 tumors, our current protocol
      indicates neoadjuvant chemotherapy in conjunction with high cumulative doses of
      radiotherapy (81Gy); IMRT and/or SRT to be the preferred technique for boosting
      the primary tumor.

PMID- 12065106
TI  - An anthropomorphic phantom for quality assurance and training in gynaecological
      brachytherapy.
AB  - BACKGROUND AND PURPOSE: An anthropomorphic water filled polymethylmethacrylate
      (PMMA) phantom designed to serve as a Quality Assurance (QA) tool and a training
      aid in brachytherapy of gynaecological tumours is investigated and presented.
      Several dosimetric parameters associated with the dose rate calculation can be
      verified with the aid of this phantom such as the source positioning, its imaging
      reconstruction from radiographs and the accuracy of the algorithm used for manual
      or computer dose rate calculation. MATERIAL AND METHODS: The phantom walls and
      the internal structure are 5mm thick and consist of PMMA, in the form of the
      abdomen taken from a female Alderson Phantom Marker points representing the
      organs of interest were determined from computed tomography scans of a patient of
      similar size. Three PMMA inserts designed to hold a Farmer type ionization
      chamber of 0.6 cm(3) were positioned at the points to represent the bladder,
      rectum and point A. The formalism proposed by the IAEA TRS-277 dosimetry protocol
      was used for the conversion of readings of the ionization chamber to dose rate
      values with a modification to take into account the dose rate gradient in the
      detector. Five 137Cs sources were used and the dose rate was evaluated by
      measurements and Monte Carlo simulations using the PENELOPE code. Four different
      treatment planning systems with different algorithms and source reconstruction
      techniques were also used in this investigation and compared with the manual dose
      rate calculations made using Karen and Breitman's tables. RESULTS: The dose rate
      calculations performed with Monte Carlo and the four treatment planning systems
      are in good agreement with the experimental results as well as with the manual
      calculations when the colpostat shielding and the tandem attenuation are taken
      into account. The comparison between experiment and calculations by the four
      treatment planning systems shows a maximum variation of 5.1% between the
      calculated and measured dose rate at the point A. CONCLUSIONS: This phantom is
      suitable for use during the acceptance tests of treatment planning systems and
      applicators, as educational tool, for dosimetric research problems and for the QA
      of brachytherapy sources.

PMID- 12065107
TI  - The impact of patient positioning on the adequate coverage of the uterus in the
      primary irradiation of cervical carcinoma: a prospective analysis using magnetic
      resonance imaging.
AB  - BACKGROUND AND PURPOSE: The intention of this prospective study is to assess the
      influence of different patient positionings and the use of belly boards on the
      coverage of the uterus by standard radiation fields. MATERIAL AND METHODS: In 21
      women with carcinoma of the uterine cervix magnetic resonance imaging (MRI) scans
      in prone patient position with and without belly board and computed tomography
      (CT) scans in supine position were analysed after superimposing standard pelvic
      box fields. Further, all patients underwent a second MRI field control in prone
      position with belly board to detect intraindividual variations in the uterus
      position during treatment. RESULTS: Standard portals did not completely cover the
      uterus in supine position in 7/21 (33%), in prone position with belly board in
      7/21 (33%) and without belly board in 5/21 (24%). Insufficient uterine coverage
      was found only in the anteroposterior direction. The mean distance (+/- standard
      deviation) between the field borders of the lateral portals and the uterus was in
      supine position anteriorly 3.4 cm (+/-2.2 cm) and posteriorly 1.8 cm (+/-1.3 cm),
      in prone position with belly board anteriorly 2.2 cm (+/-2.7 cm) and posteriorly
      2.6 cm (+/-1.6 cm), prone without belly board anteriorly 3.3 cm (+/-2.4 cm) and
      posteriorly 1.9 cm (+/-1.1 cm). The difference was statistically significant
      between supine and prone position with belly board and between prone position
      with and without belly board. Repeated MRI controls during therapy showed no
      significant changes compared to the MRIs at the beginning of therapy.
      CONCLUSIONS: The use of standard radiation fields results in a high percentage of
      geographical misfits. Three-dimensional treatment planning is a prerequisite for
      adequate uterus coverage.

PMID- 12065108
TI  - Inaccuracy in manual multisegmental irradiation in coronary arteries.
AB  - PURPOSE: Retrospective evaluation of the accuracy of manual multisegmental
      irradiation with a source train for irradiation of long (re)stenotic lesions in
      coronary arteries, following percutaneous transluminal coronary angioplasty
      (PTCA). MATERIAL AND METHODS: Thirty-six patients were treated with intracoronary
      irradiation following PTCA with manual multisegmental irradiation. These patients
      were included in the multicenter, multinational 'European Surveillance Registry
      with the Novoste Beta-Cath system' (RENO). In all 36 patients the target length
      (i.e. PTCA length plus 5-mm margin at each side) was too long for the available
      source train lengths (30 and 40 mm). In 33 patients the radiation delivery
      catheter was manually positioned twice and in three patients three times in
      series, trying to avoid any gap or overlap. The total number of junctions was 39.
      Following a successful PTCA procedure the site of angioplasty was irradiated
      using the Novoste Beta-Cath afterloader with a 5-F non-centered catheter which
      accommodates the sealed beta-emitting (90)Sr/(90)Y source train or dummy source
      train. Radiation was delivered first to the distal part of the target length.
      Fluoroscopic images of this source position were stored in the computer memory.
      For irradiation of the proximal part of the target length, the delivery catheter
      had to be retracted over a distance equal to the source length used for the
      distal part. This was done by a continuous overlay video loop with ECG-gated
      replay of the image stored in the computer memory. The dummy source was used to
      position the delivery catheter so that the junction between both source positions
      was as precise as possible. Measurements of gap or overlap between the source
      positions were performed retrospectively on printed images. Doses were
      calculated, in accordance with the Novoste study protocol, at a distance of 2 mm
      from the source axis (=dose prescription distance) in several points along the
      irradiated length. RESULTS: Interventional or PTCA length varied between 33 and
      95 mm. The lesion sites were in the left anterior descending artery, (n=6), right
      coronary artery (n=20), left circumflex artery (n=6) and one vein graft. The
      administered radiation dose was determined by the vessel diameter and the
      presence of a stent. This dose, prescribed at a distance of 2 mm from the source
      axis, varied between 16 and 22 Gy. No gap or overlap was seen between the two
      source trains in only two out of 39 cases. In 16 cases there was a gap ranging
      between 0.6 and 9.6 mm and 18 cases showed an overlap of 0.5-14.4 mm. In three
      patients the measurement was not possible. In case of a gap the minimal dose
      calculated at 2 mm from the source axis varies between 0 and 87% of the
      prescribed dose, depending on the distance between both sources. In case of
      overlap the maximal dose varies between 110 and 200% of the prescribed dose at 2
      mm from the source axis. CONCLUSIONS: The results show the inaccuracy of manual
      multisegmental irradiation using a source train in coronary arteries, causing
      unacceptable dose inhomogeneities at a distance of 2 mm from the source axis at
      the junction between both source positions. Moreover, a perfect junction will
      never be possible due to movement of the non-centered radiation delivery catheter
      in the vessel lumen, as applied in this study. Manual multisegmental irradiation
      is therefore not recommended. Using longer line sources or source trains or
      preferably an automated stepping source is a more reliable and safer technique
      for treatment of long lesions.

PMID- 12065109
TI  - Possible impact of iridium-192 source centering on restenosis rate after femoro
      popliteal angioplasty and endovascular brachytherapy in Vienna-2 study.
AB  - PURPOSE: Endovascular brachytherapy (EVBT) has been proven to significantly
      reduce restenosis after percutaneous transluminal angioplasty (PTA). The object
      of this analysis was to assess the possible correlation between iridium-192
      source non-centering and angiographic-determined restenosis. MATERIALS AND
      METHODS: A total of 113 patients with long-segment lesions of the superficial
      femoro-popliteal artery (SFA) were randomized to receive either PTA alone or PTA
      followed by EVBT in the Vienna-2 study. This analysis was performed on a subgroup
      of 34 out of 57 patients, who received PTA+EVBT. Angiographic restenosis was
      defined as lumen reduction of more than 50%. Angiograms taken immediately after
      PTA (34 patients) and at follow-up (25 patients) were analyzed. The distance
      between the vessel wall and the actual position of the source at the time of EVBT
      was measured (in mm) and correlated with the follow-up vessel lumen diameter.
      Measurements were performed at points at a distance of 10 mm from each other. The
      dose was determined at the luminal surface and at the reference depth of 2 mm
      into the vessel wall for different distances from the source. RESULTS: Among the
      622 measured points, 62 (10.0%) were within restenotic areas; 560 (90.0%) were in
      arterial segments without proven angiographic restenosis. As far as source
      centering is concerned, 7.9% of restenotic points were observed when the maximum
      distance to the arterial wall was <3 mm and 9.6% for 4 mm, respectively. The
      percentage of restenotic points increased up to 15.9% when the maximum distance
      to the arterial wall was 5 mm and reached 22.2% when it was >5 mm. CONCLUSIONS:
      The proportion of restenotic points significantly increased with source non
      centering. This observation was interpreted as being related to a decrease in
      dose at the target. When the maximum distance between the source and the vessel
      surface was >5 mm, the dose at the reference depth (2 mm into the vessel wall)
      decreased to values lower than 5 Gy.

PMID- 12065110
TI  - Coronary stent traversed volume during the cardiac cycle defined as a target for
      high-precision radiotherapy by using biplane angiograms.
AB  - Three-dimensional reconstructions of 19 coronary artery stents from biplane
      angiograms were used for measurement of the volume through which the stents
      traversed during the cardiac cycle. This volume, less than 0.8% of the whole
      heart volume in all patients, represents a target volume for high-precision
      radiotherapy to treat coronary artery in-stent restenosis.

PMID- 12065111
TI  - Late radiation effects in the dog brain: correlation of MRI and histological
      changes.
AB  - PURPOSE: To determine the correlation between sequential changes in the brain of
      dogs after irradiation, as detected by magnetic resonance imaging (MRI), with the
      eventual appearance of histological lesions. Histology was performed 77-115 weeks
      after irradiation. MATERIALS AND METHODS: Groups of five beagle dogs were
      irradiated to the brain with single doses of 10, 12, 14 or 16 Gy of 6 MV photons,
      at the 100% iso-dose. Sequential MRIs were taken to detect changes in the brain
      for 77-115 weeks after irradiation. Dose-effect relationships were established
      for changes in the brain as detected by MRI, computerized tomography (CT), gross
      morphology and histology. The doses that caused a specified response in 50% of
      the animals (ED(50)+/-SE) were calculated from these dose-effect relationships
      for each endpoint. RESULTS: The ED50 values (+/-SE) for focal and diffuse changes
      on T2-weighted MR images were 11.0+/-1.1 and 10.8+/-0.9 Gy, respectively. The
      ED50 values (+/-SE) for contrast enhancement on T1-weighted MR images and on CT
      were 13.4+/-0.6 and 13.0+/-0.6 Gy, respectively. It was 11.4+/-0.6 Gy for any
      type of histological lesion (haemorrhage, reactive change or glial scar) 77-115
      weeks after irradiation. For a macroscopic lesion the ED50 (+/-SE) value was
      13.0+/-1.1 Gy. CONCLUSIONS: The presence of focal or diffuse changes on T2
      weighted MR images was the best indicator for the eventual appearance of any type
      of histological lesion in the dog brain after irradiation with single doses of
      photons. The ED50 for any histological lesion did not differ significantly from
      the ED50 for a focal (P>0.35) or diffuse (P=0.3) change on T2-weighted MR images.

PMID- 12065112
TI  - Assessment of the acceptability of the Elekta multileaf collimator (MLC) within
      the Corvus planning system for static and dynamic delivery of intensity modulated
      beams (IMBs).
AB  - The sliding window technique used for static and dynamic segmentation of
      intensity modulated beams is evaluated. Dynamic delivery is preferred since the
      resulting distributions correspond better with the calculated distributions, the
      treatment beam is used more efficiently and the delivery is less sensitive to
      small variations in the accuracy of the multileaf collimator (MLC).

PMID- 12065113
TI  - Gray-white matter discrimination--a possible marker for brain damage in heat
      stroke?
AB  - INTRODUCTION/OBJECTIVE: Heat stroke (HS) is a common medical emergency which
      carries high morbidity and morality. This study was designed to describe the
      pattern of central nervous system (CNS) changes as detected by brain CT scan in a
      case series of six patients suffering from classical and exertional HS. METHODS
      AND PATIENTS: All the patients were admitted in critical condition during the
      heat wave in the summer of 1999 in Israel. Each was in deep coma with a measured
      core temperature of over 40 degrees C upon admission to the emergency department.
      RESULTS: Aggressive cooling measures decreased the core temperature to <38
      degrees C within 30 min following admission. Two patients (33.3%) died. One of
      the survivors remained in a vegetative state. Brain CT studies carried out within
      4 days of admission in all the patients revealed severe loss of gray-white matter
      discrimination (GWMD) without signs of acute bleed or significant focal lesion,
      findings that persisted in repeated brain CTs in one patient who remained in a
      vegetative state. DISCUSSION AND CONCLUSIONS: Loss of GWMD may represent an early
      and sensitive indication of severe brain damage in patients with severe HS.
      Further studies in larger groups of patients are warranted in order to determine
      whether the appearance of GWMD in brain CTs of patients with HS has prognostic
      value.

PMID- 12065114
TI  - MR imaging and in vivo proton spectroscopy of the brain in neonates with hypoxic
      ischemic encephalopathy.
AB  - INTRODUCTION: A number of studies have suggested the potential utility of in vivo
      proton MR spectroscopy for the evaluation of brain injury in the asphyxiated
      neonates. We present our initial experience with in vivo proton MR spectroscopy
      in neonates who were diagnosed as having hypoxic injury on clinical examination
      and the severity of the insult was graded using Sarnat staging. METHODS AND
      MATERIAL: MR imaging and in vivo proton MR spectroscopy was performed in 16
      neonates with hypoxic ischemic encephalopathy (HIE) to correlate the imaging and
      metabolite abnormality with clinical severity of the condition at the time of
      insult and with outcome at 2 months of age. The ratios of different metabolites
      were calculated as observed on MR spectroscopy from an 8 ml voxel that included
      thalami, basal ganglia and part of the ventricular system using spin echo
      technique with an echo time of 135 ms. RESULTS AND DISCUSSION: The results of the
      spectroscopy were compared with imaging abnormalities and Sarnat's clinical
      staging of HIE. MR Imaging abnormalities included basal ganglia, thalamic and
      periventricular hemorrhage and periventricular hyperintensities and were noticed
      in 8/16 neonates with different stages of HIE. Maximum imaging abnormalities were
      noted in stage II (6/9) followed by stage III (1/2) and stage I (1/5),
      respectively. The alpha-Glx resonance at 3.76 ppm was seen in 14/16, Glycine at
      3.56 ppm (Gly) was seen in 10/16 and Lactate (L) at 1.33 ppm was observed in 4/16
      neonates with HIE. CONCLUSION: MR spectroscopy was more sensitive than imaging in
      detecting the insult due to HIE and increased concentration of alpha-Glx/Cr and
      Gly/Cr correlated better with severity of the HIE. The demonstration of L was
      associated with poor outcome.

PMID- 12065115
TI  - Iatrogenic vertebral artery pseudoaneurysm: US, CT and MRI findings.
AB  - Vertebral artery pseudoaneurysm (VAP) is the result of the penetrating neck
      trauma, chiropractic manipulation, vasculopathies and rarely iatrogenic due to
      internal jugular vein (IJV) catheterization. It should be identified and treated
      immediately because of its potential risk of rupture. We present a case of a
      right VAP resulting from jugular vein catheterization, with the Doppler
      ultrasonography (US), Computed tomography (CT) and magnetic resonance imaging
      (MRI) findings. Although angiography is a well known gold standard modality,
      Doppler US, CT and MRI findings can be sufficient to demonstrate VAP.

PMID- 12065116
TI  - Expanding experience with spontaneous dermoid rupture in the MRI era: diagnosis
      and follow-up.
AB  - With widespread use of CT and MR imaging, experience with spontaneous dermoid
      rupture has significantly increased. What was previously believed to be a
      generally severe or even fatal accident, being the diagnosis made either at
      surgery or autopsy, or in patients with such consequent conditions as chemical
      meningitis or obstructive hydrocephalus, now appears to be more frequent than
      previously thought, and there is some evidence that it may also cause only a
      slight symptomatology or even be quite asymptomatic. We reviewed the clinical and
      imaging data of our series of five patients with spontaneously ruptured dermoids,
      spinal in one case, and intracranial supratentorial in four. These had their
      diagnosis following mild symptoms (number two cases) or incidentally (number two
      cases); the spinal tumor caused acute bladder dysfunction, possibly while
      undergoing rupture, and was associated with indolent intracranial fat spread.
      Three of the patients also had MR demonstration of asymptomatic persistence of
      fat spread in the subarachnoid spaces, respectively, 3, 4, and 5 years after
      rupture. One of the five cases, concerning a parasellar dermoid followed up over
      6 years, provides the first demonstration of MR signal intensity change of the
      tumor prior to rupture.

PMID- 12065117
TI  - Focal cerebral involvement by neurobrucellosis: pathological and MRI findings.
AB  - Central nervous system involvement by brucellosis is infrequent and usually
      presents as acute meningoencephalitis. Neurobrucellosis presenting as a focal
      brain mass has rarely been demonstrated on imaging studies. We describe the
      imaging and pathologic findings in a child affected by neurobrucellosis with
      focal cortico-subcortical involvement.

PMID- 12065118
TI  - Preoperative transcatheter arterial infusion chemotherapy for locally advanced
      breast cancer (stage IIIb) for down-staging and increase of resectability.
AB  - OBJECTIVES: To evaluate the clinical usefulness of preoperative transcatheter
      arterial infusion chemotherapy (TAIC) for locally advanced breast cancer.
      METHODS: Seven patients with unresectable locally advanced breast cancer (stage
      IIIb) underwent TAIC percutaneously 1-3 times (mean, 1.7 times) until tumors
      became resectable. Anticancer drugs were injected into both the internal mammary
      and the distal subclavian arteries. RESULTS: There was no major complication
      related to the procedure. The mean tumor size was significantly decreased from
      10.0+/-3.9 to 5.1+/-2.5 cm (P=0.0086). Skin and muscle invasions were improved in
      two patients (28%) and lymph nodes disappeared in one patient (14%). In two
      patients (28%), down-staging was achieved from stage IIIb to stage IIIa. All
      tumors turned into resectable, and mastectomy was performed with a mean period of
      35 days (range 9-60 days) after TAIC. Marked decrease in tumor size allowed one
      patient to receive breast-conserving surgery. There was no local recurrence in
      any patient. However, five patients (71%) experienced distant metastases. The 3
      year disease free and overall survival were 0 and 71.4%, respectively.
      CONCLUSIONS: TAIC for locally advanced breast cancer is useful in reducing tumor
      size and achieving down-staging in a relatively short period, leading to an
      expanded surgical indication.

PMID- 12065119
TI  - Application of dynamic MRI to differentiating odontogenic myxomas from
      ameloblastomas.
AB  - It is often difficult to radiographically distinguish odontogenic myxomas from
      ameloblastomas. In the present study, we tried to differentiate odontogenic
      myxomas from ameloblastomas using dynamic magnetic resonance imaging (dynamic
      MRI). Two cases of ameloblastoma with cystic components and two cases of
      odontogenic myxoma were compared by dynamic MRI. The dynamic MRI features of
      solid areas of ameloblastomas showed a rapid enhancement, reaching maximum
      contrast at 45-60 s, and maintained these enhancement levels or showed a gradual
      wash-out to 600 s thereafter; in contrast, those of the cystic areas of
      ameloblastomas showed no enhancement. The dynamic MRI features of the whole area
      of odontogenic myxomas (we considered the whole area to be the tumor substance in
      the odontogenic myxomas, as based on histopathological examinations) showed a
      gradual increase in enhancement at 500-600 s. The central portions of the
      odontogenic myxomas, which did not appear to be enhanced on Gd-T1 weighted images
      also showed a gradual increase in enhancement at 500-600 s, though the increase
      was minimal. These results indicate that the dynamic MRI features of odontogenic
      myxomas are different from those of ameloblastomas. Therefore, dynamic MRI may be
      a useful tool for diagnosis of myxoma.

PMID- 12065120
TI  - Inferomedially projecting pneumatised secondary middle turbinate.
AB  - Secondary middle turbinate (SMT), a rare variation of the nasal cavity, is a bony
      projection covered by soft tissue that arises from the lateral nasal wall. It is
      almost always bilateral and usually projects superomedially without any
      ostiomeatal unit obstruction. Herein, we report a case of bilateral
      inferomedially projecting secondary middle turbinates, one of which is
      pneumatised and hypertrophied, resembling a large ethmoid bulla extending into
      the middle meatus. The recognition of this variation is important since it may
      predispose to inflammatory sinus disease, by narrowing the ostiomeatal unit.

PMID- 12065121
TI  - Overuse and sports-related injuries of the ankle and hind foot: MR imaging
      findings.
AB  - Professional and recreational sporting activities have increased substantially in
      recent years and have led to a rise in the number of sports-related and overuse
      injuries. Magnetic resonance (MR) imaging has become an important tool for
      evaluating the lower leg for providing the necessary information for patient
      management and rehabilitation following this injury. The purpose of this essay is
      to give an overview of the MR findings of common overuse injuries and sports
      related injuries to the bones and soft-tissue structures of the hind foot and
      ankle.

PMID- 12065122
TI  - Congenital anterior dislocation of the radial head: a case with radiographic
      findings identical to traumatic dislocation.
AB  - Differentiation of congenital unilateral dislocation of the radial head from a
      traumatic dislocation depends mainly on the radiographic findings. Here, we
      report a case of congenital unilateral anterior radial head dislocation with
      radiographic findings identical to traumatic dislocation.

PMID- 12065123
TI  - Bone marrow ill-defined hyperintensities with tarsal coalition: MR imaging
      findings.
AB  - INTRODUCTION: To report the occurrence and pattern of ill-defined subchondral
      hyperintensities on Magnetic Resonance (MR) imaging in patients with
      talocalcaneal coalition (TCC). METHODS AND MATERIAL: MR imaging of both feet was
      performed in 10 consecutive patients with 14 TCCs. There were eight males and two
      females with ages ranging from 9-52 years (mean 25 years). Twelve of the 14 TCCs
      were symptomatic. MR imaging sequences included T1- and T2-weighted as well as
      STIR images. The images were evaluated for the presence, extent and location of
      ill-defined subchondral hyperintensities on MR images in the hindfoot. RESULTS:
      Ill-defined subchondral hyperintensities on MR imaging were present in 12 (86%)
      of the 14 hindfeet with TCCs. Two of these were without symptoms. No
      abnormalities were seen in two symptomatic hindfeet. DISCUSSION AND CONCLUSION:
      In our series hyperintensities located in the subchondral bone adjacent to the
      coalition was relatively common in TCC. The presence of this specific pattern in
      the subchondral bone adjacent to the coalition may be indicative of tarsal
      coalition.

PMID- 12065124
TI  - Low-grade chondrosarcomas: a difficult target for radionuclide imaging. Case
      report and review of the literature.
AB  - Bone scan with Tc-99m (technetium) diphosphonate is sensitive, but non-specific
      for musculoskeletal tumors. Tl-201 (thallium), Tc-99m-sestamibi, Tc-99m
      tetrofosmin, and F-18-fluorodeoxyglucose (F-18-FDG) can visualize tumors more
      specifically and are therefore useful in orthopedic oncology. However,
      cartilaginous tumors are characterized by histological and biological features,
      which potentially impair specific radionuclide imaging. A case of a patient with
      a low-grade primary chondrosarcoma of the femur and a false negative Tl-201 scan
      is presented. Tc-99m-based tumor-localizing compounds (sestamibi, tetrofosmin),
      as well as metabolic and receptor-imaging radiopharmaceuticals have also been
      reported to fail in low-grade chondrosarcomas imaging. Low cellularity,
      mitochondrial specialization and the presence of an efflux membrane pump may
      contribute to poor imaging. A negative Tl-201 or Tc-99m-sestamibi scan should be
      interpreted with caution, when the possibility of a chondrosarcoma is not
      negligible.

PMID- 12065125
TI  - Sonographic measurements of the liver, spleen and kidney dimensions in the
      healthy term and preterm newborns.
AB  - This study was conducted in order to assess normal liver, spleen and kidney
      dimensions in premature and term newborns and determine the acceptable range. A
      total of 253 (99 preterm and 154 term) healthy newborns were evaluated within the
      first week of life by sonography. Gestational age ranged from 24 to 41 weeks,
      weight ranged from 638 to 4800 g. Measurements were compared with gestational
      age, weight and height of the infants. Normal ranges for kidney, liver and spleen
      measurements according to gestational age and weight were obtained. We found that
      weight showed the best correlation with any one of the mentioned organ
      dimensions.

PMID- 12065126
TI  - Arterial embolization of a secondary aneurysmatic bone cyst of the thoracic spine
      prior to surgical excision in a 15-year-old girl.
AB  - We report on a 15-year-old girl with a secondary aneurysmatic bone cyst of the
      thoracic spine with extension into the spinal canal on the basis of an
      osteoblastoma. Surgical treatment was facilitated by preoperative embolization of
      the highly-vascular tumor. Excision of the tumor was performed without extensive
      intraoperative blood loss. Following excision, transpedicular-stabilization of
      the spinal column was achieved using a fixateur intern. We conclude that
      superselective embolization of benign lesions of the spinal column constitutes a
      feasible means of reducing intraoperative bleeding complications, thus enhancing
      resectability.

PMID- 12065127
TI  - Arteriovenous fistula. Quiz case.

PMID- 12065130
TI  - Effect of early pregnancy on a previous lower segment cesarean section scar.
AB  - OBJECTIVE: To summarize the manifestation, diagnosis, and early management of
      early pregnancy on a previous cesarean section scar. METHOD: Fifteen cases of
      early pregnancies implanted on previous cesarean section scars were diagnosed and
      treated in two obstetrical centers. RESULTS: The 15 patients had light, painless
      vaginal bleeding and their serum beta-subunit human chorionic gonadotropin (beta
      HCG) was elevated. The interval between cesarean section and admission ranged
      from 6 months to 12 years (7.1+/-3.6 years). Doppler and real-time ultrasonic
      examinations demonstrated an enlargement of the previous cesarean section scar in
      the lower segment, a gestational sac or a mixed mass attached to the cicatrix,
      and a very thin myometrium between the gestational sac and the bladder wall.
      Serum beta-HCG dropped to normal in 12 of the 15 patients following treatment
      with crystalline trichosanthin injected into the cervix followed by oral
      mifepristone, intramuscular injections of methotrexate, or other appropriate
      treatment. Two patients underwent total hysterectomy due to massive vaginal
      bleeding. The remaining patient was misdiagnosed with choriocarcinoma and also
      had total hysterectomy. CONCLUSION: Pregnancy on a previous lower segment
      cesarean section scar is rare but very dangerous. Early diagnosis and effective
      conservative drug treatment may be instrumental in decreasing the occurrence of
      uterine rupture.

PMID- 12065131
TI  - Association of the Gln27Glu polymorphism of the beta-2-adrenergic receptor with
      preterm labor.
AB  - OBJECTIVES: To investigate a potential association between the beta-2-adrenergic
      receptor (B2AR) polymorphisms occurring at amino acid positions 16 (Arg16Gly) and
      27 (Gln27Glu) and preterm labor. METHODS: Eighty patients with preterm labor and
      76 control subjects were analyzed by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). RESULTS: A significant association was
      found between Gln27Glu substitution and preterm labor (P=0.001). The frequency of
      Gly16 and Glu27 alleles were found to be higher in patients than in control women
      (0.54 vs. 0.48 and 0.42 vs. 0.26, respectively), and the odds ratio for the
      occurrence of preterm labor was 2.14 (95% CI, 1.32-3.46; P=0.002) for the Glu 27
      allele. An early delivery was noted in 52.5% of patients. CONCLUSION: The
      Gln27Glu polymorphism of the B2AR gene may have a role in molecular pathogenesis
      of preterm labor. Glu27 allele in patients with preterm labor might be a risk
      factor for deliveries before 37 weeks of gestation.

PMID- 12065132
TI  - Lamellar bodies as a diagnostic test of fetal lung maturity.
AB  - OBJECTIVES: To determine the number of lamellar bodies in the amniotic fluid
      indicating fetal lung maturity and to define the effectiveness of a diagnostic
      test in a healthy pregnant population. METHODS: The study took place at the
      Hospital General de Zona #16 Centro Medico Nacional del Instituto Mexicano del
      Seguro Social. Torreon, Coahuila, Mexico, where 264 pregnant women were followed
      up from August 1997 to October 1998. The women presented in labor between 26 and
      41 weeks of gestation. Amniotic fluid was obtained during cesarean section or
      from the vaginal pool and lamellar bodies were counted without prior
      centrifugation in Cell-Dyn 3000's channel for blood platelets. Results were
      masked for neonatologists. RESULTS: The prevalence of respiratory distress
      syndrome (RDS) was found to be 14.9%. At the 8200/microl threshold, sensitivity
      was: 15.4% (95% CI=5.9-30.5%), specificity: 99.6% (95% CI=97.5-99.9%), positive
      predictive value (PPV): 85.7, negative predictive value (NPV): 87.1, likelihood
      ratio for a negative test (LR-): 0.85, and likelihood ratio for a positive test
      (LR+): 85.7. At the 57 000/microl level, sensitivity was: 92.3% (95% CI=79.1
      98.3%), specificity: 70.9% (64.4-76.7%), PPV: 35.6, NPV: 98.1, LR-: 0.11, and
      LR+: 3.17. When the cut-off point was 79000/microl, sensitivity was: 100.0%,
      specificity: 43.0% (95% CI=36.5-49.8%), PPV: 23.5, NPV: 100.0, LR+: 34.3, and LR
      : less than 0.001. CONCLUSIONS: Counting lamellar bodies is a quick, readily
      available, and very effective test.

PMID- 12065133
TI  - Hospitalization vs. outpatient care in the management of triplet gestations.
AB  - OBJECTIVE: To compare the course and outcome of triplet gestations under a
      preventive care strategy that includes hospitalization, surveillance, bed rest,
      and daily specialized care from the beginning of the second trimester, with
      pregnancies managed according to the Croatian standard outpatient care protocol
      for multiplets. METHODS: A retrospective study of 79 triplet pregnancies.
      Preventive hospitalization from the beginning of the second trimester, with
      complete bed rest and all necessary interventions, was chosen by 55 women (Group
      I). The remaining 24 women (Group II) elected the standard outpatient protocol
      for multiple pregnancies. Outpatient management with prophylactic bed rest was
      initiated at home as soon as the multiple pregnancy was diagnosed. After 28 weeks
      of gestation, all outpatients were hospitalized until delivery irrespective of
      symptoms. RESULTS: There was no difference between the groups regarding maternal
      age, race, pre-pregnancy weight and height, weight gain during the first 24 weeks
      of pregnancy, or the proportion of pregnancies achieved with assisted
      reproductive technology. Four out of 55 women (7.2%) from Group I and 4 out of 24
      women (12.5%) from Group II had monochorionic triplet pregnancies (P=n.s.).
      Nulliparity was more frequent in Group I than in Group II (P=0.006). Elective
      cesarean delivery was significantly more frequent in Group I (46 out of 55
      gestations, 72.7%) than in Group II (9 out of 24 gestations, 37.5%), P=0.024.
      Gestational age at delivery and mean birth weight were significantly higher in
      Group I than in Group II (P<0.001). Deliveries up to 28 weeks of pregnancy were
      infrequent in Group I (P=0.02). Thirty-three gestations in Group I (60%) and 6
      (25%) in Group II had a duration of 33-36 weeks (P<0.001). Two out of 55 triplet
      gestations in Group I (3.6%) and 4 out of 24 in Group II (16.7%) ended in
      spontaneous abortion (P=0.053). The survival of the three triplets was more
      frequent in Group I than in Group II (P=0.048). For gestations reaching 24 weeks
      or more, the fetal and perinatal death rate was significantly lower in Group I
      (P<0.001). In Group I the intrauterine death rate for fetuses weighing 1500 g or
      less was also significantly lower (P=0.007), and the early neonatal death rate
      was almost half (15.8 vs. 28.9%, P=0.157). There were no differences in other
      pregnancy complications between the two groups except significantly more frequent
      preterm premature rupture of membranes and preterm labor requiring parenteral
      tocolysis in Group II (P=0.042 and 0.036, respectively), and significantly more
      frequent fetal growth retardation in Group I (P<0.001). CONCLUSION: Preventive
      hospitalization offers a better outcome for triplets even though prolonged
      hospitalization and all other procedures necessary to achieve optimal pregnancy
      outcome are also offered in the Croatian standard outpatient care protocol for
      multiplet pregnancies.

PMID- 12065134
TI  - Imiquimod 5% cream in the treatment of anogenital warts in female patients.
AB  - OBJECTIVE: To investigate the efficacy and safety of imiquimod 5% cream in the
      treatment of anogenital warts in a female population. METHODS: In two open-label
      studies, female patients with anogenital warts applied imiquimod 5% cream three
      times a week for up to 16 weeks. Patients who cleared their warts were monitored
      for a 6-month follow-up period. Patients could be re-treated with imiquimod 5%
      cream for up to an additional 16 weeks if their warts recurred or new warts
      developed during the follow-up period. The treatment period could also be
      extended for up to an additional 16 weeks if patients only experienced partial
      clearance during the initial 16-week treatment period. RESULTS: Of the female
      patients who applied imiquimod 5% cream, 75% (449/600) experienced complete
      clearance of their warts (treatment failure analysis). This includes 46 patients
      who experienced total clearance when they applied imiquimod for longer than 16
      weeks as their warts had only partially cleared in the initial 16 weeks of
      therapy. During the 6 months of follow-up after the initial treatment period, 15%
      of patients had recurrent warts. Thirty-nine (75%) of those patients experienced
      total clearance again after they re-applied imiquimod for up to an additional 16
      weeks. The most frequently observed local skin reaction was erythema. CONCLUSION:
      In these studies, imiquimod 5% cream was an effective and well-tolerated
      treatment for anogenital warts in females and continued to be safe and effective
      in the small proportion of patients who needed to re-apply imiquimod after wart
      recurrence.

PMID- 12065135
TI  - Cardiac troponin I levels in umbilical cord blood.

PMID- 12065136
TI  - The partograph in daily practice: it's quality that matters.

PMID- 12065137
TI  - Preoperative management of anemia to avoid blood transfusion.

PMID- 12065138
TI  - Cutaneous metastasis of gestational choriocarcinoma.
AB  - A 40-year-old woman presented with subcutaneous masses on her chest wall,
      abnormal vaginal bleeding and an enlarged uterus. Chest X-ray and liver
      ultrasound revealed metastatic disease to these sites, respectively. A urine
      human chorionic gonadotrophin assay was positive. A biopsy of the chest wall
      lesion and endometrium revealed choriocarcinoma. Treatment with methotrexate,
      actinomycin-D and cyclophosphamide led to complete resolution of the disease on
      examination, X-ray and ultrasound scans. The urinary pregnancy test became
      negative.

PMID- 12065139
TI  - Hormone replacement therapy and menopause: attitude, information, and compliance
      among Israeli nurses.

PMID- 12065140
TI  - Treatment of premenstrual syndrome with a carbohydrate-rich beverage.

PMID- 12065141
TI  - Female circumcision and obstetric complications.
AB  - OBJECTIVES: To examine whether complications at delivery are associated with
      female circumcision. METHOD: One thousand eight hundred and fifty-one women
      seeking family planning or antenatal care in three south-west Nigerian hospitals
      were interviewed and had a medical exam. The prevalence of complications at
      delivery for uncircumcised women and circumcised women with type 1 (partial or
      total removal of the clitoris) or type 2 (partial or total removal of the
      clitoris and part or all of the labia minora) were determined. Associations
      between self-reported complications at delivery and clinic-reported type of
      circumcision were analyzed using bivariate and multivariate logistic regression.
      RESULT: Forty-five percent were circumcised; 71% had type 1 and 24% had type 2.
      Circumcised women had significantly higher risks of tearing and stillbirths when
      all pregnancies were analyzed. CONCLUSION: Circumcised women experienced more
      obstetric complications, while there was no significant difference between women
      with type 1 and type 2.

PMID- 12065142
TI  - Preventing postpartum hemorrhage in low-resource settings.
AB  - OBJECTIVES: To review the literature to determine the most effective methods for
      preventing postpartum hemorrhage (PPH), the single most important cause of
      maternal death worldwide. METHODS: Systematic review of published randomized
      controlled trials and relevant reviews. RESULTS: Review of the literature
      confirms that active management of the third stage of labor, especially the
      administration of uterotonic drugs, reduces the risk of PPH due to uterine atony
      without increasing the incidence of retained placenta or other serious
      complications. Oxytocin is the preferred uterotonic drug compared with
      syntometrine, but misoprostol also can be used to prevent hemorrhage in
      situations where parenteral medications are not available (e.g. at home births in
      developing countries). CONCLUSIONS: The use of active management of the third
      stage of labor to prevent PPH due to uterine atony should be expanded, especially
      in developing country settings.

PMID- 12065143
TI  - Program note. Using UN process indicators to assess needs in emergency obstetric
      services: Bhutan, Cameroon and Rajasthan, India.

PMID- 12065144
TI  - FIGO staging for gestational trophoblastic neoplasia 2000. FIGO Oncology
      Committee.

PMID- 12065145
TI  - Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the
      alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat.
AB  - The effect of oral administration of Rosmarinus officinalis L. (Lamiaceae) on
      CCl(4)-induced acute liver injury was investigated. Rats were daily treated with
      the plant extract at a dose of 200 mg/kg corresponding to 6.04 mg/kg of carnosol
      as determined by reverse phase high-performance liquid chromatography. The
      treatment was initiated 1 h after CCl(4) administration and Rosmarinus
      officinalis fully prevented CCl(4) effect on hepatic lipid peroxidation after 24
      h of CCl(4) administration. The increase in bilirubin level and alanine
      aminotransferase activity in plasma induced by CCl(4) was completely normalized
      by Rosmarinus officinalis. The treatment also produced a significant recovery of
      CCl(4)-induced decrease in liver glycogen content. CCl(4) did not modify the
      activity of liver cytosolic glutathione S-transferase (GST) compared with that of
      control groups. However, Rosmarinus officinalis increased liver cytosolic GST
      activity and produced an additional increment in plasma GST activity in rats
      treated with CCl(4). Histological evaluation showed that Rosmarinus officinalis
      partially prevented CCl(4)-induced inflammation, necrosis and vacuolation.
      Rosmarinus officinalis might exert a dual effect on CCl(4)-induced acute liver
      injury, acting as an antioxidant and improving GST-dependent detoxification
      systems.

PMID- 12065146
TI  - Anti-diabetic activity of medicinal plants and its relationship with their
      antioxidant property.
AB  - Methanolic extract (75%) of Terminalia chebula, Terminalia belerica, Emblica
      officinalis and their combination named 'Triphala' (equal proportion of above
      three plant extracts) are being used extensively in Indian system of medicine.
      They were found to inhibit lipid peroxide formation and to scavenge hydroxyl and
      superoxide radicals in vitro. The concentration of plant extracts that inhibited
      50% of lipid peroxidation induced with Fe(2+)/ascorbate were food to be 85.5, 27,
      74 and 69 micro g/ml, respectively. The concentration needed for the inhibition
      of hydoxyl radical scavenging were 165, 71, 155.5 and 151 micro g/ml, and that
      for superoxide scavenging activity were found to be 20.5, 40.5, 6.5 and 12.5
      micro g/ml, respectively. Oral administration of the extracts (100 mg/kg body
      weight) reduced the blood sugar level in normal and in alloxan (120 mg/kg)
      diabetic rats significantly within 4 h. Continued, daily administration of the
      drug produced a sustained effect.

PMID- 12065147
TI  - Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5
      lipoxygenase products in polymorphonuclear leukocytes from rats.
AB  - In the present study, Nigella sativa oil (NSO), nigellone (polythymoquinone) and
      derived thymoquinone were studied to evaluate their effect on the formation of 5
      lipoxygenase (5-LO) products from polymorphonuclear leukocytes (PMNL).NSO
      produced a concentration dependent inhibition of 5-LO products and 5-hydroxy
      eicosa-tetra-enoic acid (5-HETE) production with half maximal effects (IC(50)) at
      25+/-1 micro g/ml, respectively 24+/-1 micro g/ml. Nigellone caused a
      concentration-related inhibition of 5-HETE production (IC(50): 11.9+/-0.3 micro
      g/ml). Moreover thymoquinone, the active principle of NSO inhibited the
      production of 5-LO products (IC(50): 0.26+/-0.02 micro g/ml) and 5-HETE
      production (IC(50): 0.36+/-0.02 micro g/ml) in a similar way. The effects are
      probably due to an antioxidative action. The data may in part explain the effect
      of the oil, its derived thymoquinone and nigellone in ameliorating inflammatory
      diseases.

PMID- 12065148
TI  - Ethnopharmacology of liakra: traditional weedy vegetables of the Arbereshe of the
      Vulture area in southern Italy.
AB  - An ethnobiological field study on food plants and medicinal foods traditionally
      consumed in three Arberesh (ethnic Albanian) communities in northern Lucania
      (southern Italy) document approximately 120 botanical taxa used for these
      purposes. Non-domesticated food vegetables (liakra), mostly gathered during the
      spring season, play a central role as traditional functional food. Quantitative
      ethnobotanical, ethnotaxonomical, ethnoecological, ethnogastronomical, and
      ethnopharmacological aspects related to gathering, processing, cooking and
      consumption of liakra are discussed. Unusual food species, such as Lycium
      europeaum, Centaurea calcitrapa, and a few spontaneous weedy Asteraceae and
      Brassicaceae species are locally used in the kitchen. Most of these are very
      poorly known phytochemically and phytopharmacologically. Moreover, an analysis of
      taste perception of the most commonly used botanical foods was conducted in the
      village of Ginestra. Arberesh taste classification and indigenous criteria
      related to the perception of bitter taste in considering non-cultivated plants as
      food or medicine are discussed as well.

PMID- 12065149
TI  - The antianaphylactic effects of Crinum glaucum aqueous extract.
AB  - The aqueous extract of Crinum glaucum was evaluated for its effects on antigen
      and histamine induced contraction of the ileum and on mediator release from the
      lungs of sensitized guinea pigs. The results show that the extract dose
      dependently inhibited the contractions induced by antigen and histamine in vitro
      and in vivo. The extract also inhibited, in a dose-dependent manner, the quantity
      of mediators antigenically released from the lungs and reduced the mepyramine
      resistant activity from the lungs. The results obtained indicate that the extract
      possesses antianaphylactic properties, which may account for its use as an
      antiasthmatic in traditional medicine.

PMID- 12065150
TI  - Anti-diabetic activity of Bauhinia forficata decoction in streptozotocin-diabetic
      rats.
AB  - The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water;
      35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute
      for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats
      were investigated. The physico-metabolic parameters measured were: body weight,
      food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and
      cholesterol, plasma glucose, urinary glucose and urea, and the weight of
      epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum
      longus muscles. The STZ-diabetic rats treated with decoction showed a significant
      reduction in serum and urinary glucose and urinary urea as compared to the STZ
      diabetic control, no difference being seen between decoction-treated and 
      untreated non-diabetic rats. The other physico-metabolic factors showed no
      changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism
      seen in the rats treated with Bauhinia forficata decoction does not appear to be
      linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor
      does it appear to act in a way similar to insulin or the sulfonylureas, although
      it may act by the inhibition of neoglycogenesis in a manner similar to that of
      the biguanides.

PMID- 12065151
TI  - Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent
      diabetic (NIDDM) rats.
AB  - We have studied the effect of aqueous extract of Enicostemma. littorale (2 g/kg
      p.o.) daily for 6 weeks in neonatal non-insulin-dependent diabetes mellitus
      (NIDDM) rats. To induce NIDDM a single dose injection of STZ (70 mg/kg; i.p.) was
      given to the 5-day-old pups. After 3 months of STZ injection when animals were
      confirmed as diabetic, E. littorale was administered for 6 weeks. Fasting and fed
      glucose and insulin levels in NIDDM were significantly (P<0.05) higher than
      control rats and they were significantly decreased by the treatment with E.
      littorale. Results of the oral glucose tolerance test (OGTT) showed a significant
      (P<0.05) decrease in both AUC(glucose) and AUC(insulin) values in NIDDM treated
      group. Insulin sensitivity (K(ITT)) index of NIDDM control was significantly
      lower as compared with Wistar control and this was significantly (P<0.05)
      increased after treatment with E. littorale. Treatment with E. littorale also
      decreased the elevated cholesterol, triglyceride and creatinine levels observed
      in NIDDM rats. Our data suggest that aqueous extract of E. littorale is a potent
      herbal antidiabetic. It produces an increase in insulin sensitivity, normalizes
      dyslipidaemia and provides nephroprotection in diabetic rats.

PMID- 12065152
TI  - Antinociceptive and smooth muscle contracting activities of the methanolic
      extract of Cassia tora leaf.
AB  - The leaves of Cassia tora Linn. (Family: Caesalpiniaceae) were soxhlet extracted
      with methanol. The spasmogenic effects of the extract were evaluated on guinea
      pig ileum, rabbit jejunum and mice intestinal transit. Antinociceptive activity
      of the extract was also evaluated in the mice. The LD(50) values of the extract
      in mice were >2000 mg/kg i.p. and p.o. The extract contracted smooth muscles of
      guinea pig ileum and rabbit jejunum in a concentration-dependent manner. Atropine
      reversibly blocked this activity. Mepyramine also reduced the contractile
      amplitude due to the extract in a concentration-dependent manner. The extract
      increased intestinal transit in mice dose dependently. C. tora extract
      significantly (P<0.05) reduced the number of acetic acid induced abdominal
      constrictions in mice and the effect was comparable to that of aspirin (150 mg/kg
      i.p.). The extract also significantly (P<0.05) reduced the nociceptive response
      of mice to increased force (g). The effects were dose-dependent. The studies
      suggest that the use of C. tora, traditionally, as a purgative and in the
      treatment of other ailments is justifiable.

PMID- 12065153
TI  - Screening of the topical anti-inflammatory activity of some Central American
      plants.
AB  - Hexane, chloroform and methanol extracts of seven herbal drugs used in the folk
      medicine of Central America against skin disorders (Aristolochia trilobata leaves
      and bark, Bursera simaruba bark, Hamelia patens leaves, Piper amalago leaves, and
      Syngonium podophyllum leaves and bark) were evaluated for their topical anti
      inflammatory activity against the Croton oil-induced ear oedema in mice. Most of
      the extracts induced a dose-dependent oedema reduction. The chloroform extract of
      almost all the drugs exhibited interesting activities with ID(50) values ranging
      between 108 and 498 micro g/cm(2), comparable to that of indomethacin (93 micro
      g/cm(2)). Therefore, the tested plants are promising sources of principles with
      high anti-inflammatory activity.

PMID- 12065154
TI  - Protection against radiation induced damage to spermatogenesis by Podophyllum
      hexandrum.
AB  - Aqueous extract of rhizome of Podophyllum hexandrum (RP-1) has been found to
      render protection against lethal whole body irradiation (10 Gy), damage to
      haemopoietic and gastrointestinal tissue etc. in mice. In order to assess its
      suitability from clinical point of view its effects were investigated on male
      germinal tissue in mice. Swiss albino strain 'A' male mice (10-12 weeks) were
      exposed to varied radiation doses (0.5, 2.0, 5.0 and 10 Gy) with and without 200
      mg/kg b.w. of RP-1 and sacrificed at different time periods (10, 35 and 70 days)
      to collect the tissue. Administration of RP-1, 2 h before irradiation rendered a
      significant increase in the testis weight, repopulating tubules, resting primary
      spermatocytes, stem cell survival index, sperm counts and reduction in
      abnormalities of sperm morphology, at all the time periods studied here. RP-1
      treatment alone did not generate any adverse effects. These results reveal that
      RP-1, if put to clinical application, will not be harmful to the testicular
      system.

PMID- 12065155
TI  - Inhibition of proliferation and induction of apoptosis by tetrandrine in HepG2
      cells.
AB  - Tetrandrine is a bisbenzylisoquinoline alkaloid derived from the root of
      Stephania tetrandra S. Moore, which has been reported to elicit in vitro
      cytotoxic effects on HeLa cells, and in vivo suppressive effects on mouse ascites
      tumors. In the present study, we examined the antiproliferative and apoptosis
      inducing activity of tetrandrine in HepG2 cells, a human hepatoma cell line.
      Tetrandrine showed potent cytotoxic activity in HepG2 cells (IC(50)=9.0+/-1.0
      micro M) following incubation for 48 h. Dose-dependent induction of apoptosis was
      observed by agarose gel electrophoresis and flow cytometric analysis. Treatment
      of HepG2 cells with tetrandrine resulted in the activation of caspase-3 protease,
      and subsequent proteolytic cleavage of poly(ADP-ribose) polymerase. These results
      suggest that tetrandrine is potentially useful as a
      chemotherapeutic/chemopreventive agent in hepatocellular carcinoma.

PMID- 12065156
TI  - Hypoglycaemic effect of Clausena anisata (Willd) Hook methanolic root extract in
      rats.
AB  - This study was designed to examine the hypoglycaemic effect of Clausena anisata
      (Willd) Hook [family: Rutaceae] root methanolic extract in normal
      (normoglycaemic) and in streptozotocin-treated diabetic rats. Young adult, male
      Wistar rats (Rattus norvegicus) weighing 250-300 g were used. Diabetes mellitus
      was induced in the group of diabetic 'test' rats by intraperitoneal injections of
      streptozotocin (STZ, 90 mg/kg). In one set of experiments, graded doses of the
      methanolic root extract of C. anisata (CAME, 100-800 mg/kg p.o.) were
      administered to both fasted normal and fasted diabetic rats. In another set of
      experiments, 800 mg/kg of CAME, a dose of the plant extract which produced
      maximal hypoglycaemic effect in both fasted normal and diabetic rats in the
      previous set of experiments, was used. The hypoglycaemic effect of this single
      dose of C. anisata root methanolic extract (i.e. CAME, 800 mg/kg p.o.) was
      compared with those of insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg
      p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment,
      relatively moderate to high doses of CAME (100-800 mg/kg p.o.) produced dose
      dependent, significant reductions (P<0.05-0.001) in the blood glucose
      concentrations of both fasted normal and fasted diabetic rats. On their own, both
      insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) produced
      significant reductions (P<0.01-0.001) in the blood glucose concentrations of the
      fasted normal and diabetic rats. At a dose of 800 mg/kg p.o., CAME reduced the
      mean basal blood glucose concentrations of fasted normal and fasted diabetic rats
      by 57.52 and 51.30%, respectively. C. anisata contains a diverse group of
      chemical compounds (see Table 1). Since methanol extractives of plants are
      usually known to contain many chemical compounds, each of which is capable of
      producing definite biological activities via different mechanisms, it is
      difficult to draw any logical conclusion on the mechanism of the hypoglycaemic
      effect of such a diverse mixture of chemical compounds contained in the plant
      extract used in this study. While it is possible that the hypoglycaemic effect of
      the plant extract may be due, at least in part, to its terpenoid and coumarin
      contents, the mechanism of its hypoglycaemic action remains largely speculative,
      and is unlikely to be due to the stimulation of pancreatic beta-cells and
      subsequent secretion of insulin. Although C. anisata root methanolic extract is
      less potent than insulin as an antidiabetic agent, the results of this
      experimental animal study indicate that the herb possesses hypoglycaemic
      activity; and thus lend credence to the suggested folkloric use of C. anisata
      root in the management and/or control of adult-onset, Type-2 diabetes mellitus in
      some communities of South Africa.

PMID- 12065157
TI  - Suppression of alcohol-cessation-oriented hyper-anxiety by the benzoflavone
      moiety of Passiflora incarnata Linneaus in mice.
AB  - A benzoflavone moiety has been reported recently to be responsible for the
      multifarious CNS effects of Passiflora incarnata Linneaus. In the light of the
      established usefulness of the benzoflavone moiety in counteracting the withdrawal
      effects of substances like morphine, cannabinoids and nicotine by the authors,
      the bioactive benzoflavone moiety (BZF) has been tested in mice treated with an
      addictive dose (2 g/kg, bid for 6 days) of ethyl alcohol, in order to evaluate
      its effectiveness in countering alcohol dependence. In a 7-day regimen, different
      groups of mice were administered vehicle, alcohol and alcohol+three doses (10, 20
      and 50 mg/kg of the benzoflavone moiety) of P. incarnata; all treatments
      (chronic) being administered orally, twice daily for 6 days. Similarly, three
      other groups of mice were rendered addicts upon alcohol by administration of the
      addictive dose (2 g/kg, bid for 6 days) of ethyl alcohol, and a single acute
      administration of 10, 20 and 50 mg/kg dose of benzoflavone moiety was given on
      the 7th day. In both, chronic and acute administrations, the benzoflavone moiety
      prevented significantly the expression of withdrawal effects of alcohol as there
      was a significant decrease in anxiety oriented behavior in mice that received
      benzoflavone moiety of P. incarnata. The chronic administration of P. incarnata
      with alcohol had better preventive effects than the single acute treatment with
      P. incarnata in alcohol-dependent mice.

PMID- 12065158
TI  - Antipruritic and antinociceptive effects of Chenopodium album L in mice.
AB  - The ethanolic extract from the fruits of Chenopodium album L. (FCAL), orally
      administered at doses of 100-400 mg/kg, dose-dependently inhibited scratching
      behavior induced by 5-HT (10 micro g per mouse, s.c.) or compound 48/80 (50 micro
      g per mouse, s.c.) in mice. But it failed to affect hind paw swelling induced by
      5-HT or compound 48/80 in mice at doses of 100 and 200 mg/kg and only showed a
      relatively weak inhibition on the swelling at a higher dose of 400 mg/kg. In
      addition, FCAL (200 and 400 mg/kg) significantly attenuated the writhing
      responses induced by an intraperitoneal injection of acetic acid and the
      inflammatory pain response induced by an intraplantar injection of formalin in
      mice. At a dose of 400 mg/kg, it also inhibited the neurogenic pain response of
      formalin test. In conclusion, FCAL possesses antipruritic and antinociceptive
      activities and the antinociceptive effects are not secondary to anti-inflammatory
      effects. The findings support evidence for the clinical use of FCAL to treat
      cutaneous pruritus.

PMID- 12065159
TI  - Neuropharmacological profile of Barleria lupulina Lindl. Extract in animal
      models.
AB  - Barleria lupulina Lindl. is a popular medicinal plant distributed in mountains of
      southern and western India. In the present work, the effect of methanolic extract
      of aerial parts of B. lupulina on CNS activity has been evaluated. The CNS
      activity was tested in several experimental models, in mice and rats: general
      behavior, exploratory behavior, muscle relaxant activity, conditioned avoidance
      response and phenobarbitone sodium-induced sleeping time tests. The aerial parts
      of the plant B. lupulina was extracted with methanol and the solvent was removed
      by vacuum distillation. The methanol extract (100, 200 and 300 mg/kg) showed
      reduction in general behavioral pattern (spontaneous activity, alertness,
      awareness, pain response and touch response) in a dose dependent manner. The
      extract was found to produce a significant reduction of the exploratory
      behavioral profile (Y-maze test, head dip test) and conditioned avoidance
      response with all the tested doses. The methanolic extract showed significant
      motor incoordination and muscle relaxant activity. The extract also potentiated
      phenobarbitone sodium induced sleeping time. Preliminary investigation showed
      that the methanol extract of B. lupulina has significant psychopharmacological
      activity.

PMID- 12065160
TI  - Genotoxicity of Brosimum gaudichaudii measured by the Salmonella/microsome assay
      and chromosomal aberrations in CHO cells.
AB  - The root bark of Brosimum gaudichaudii Trecul (Moraceae) is popularly used for
      treatment of vitiligo. In the present study the mutagenic activity of the aqueous
      and methanolic extract as well as of the n-butanolic fraction of this medicinal
      plant were evaluated using Salmonella typhimurium assays, TA100, TA98, TA102 and
      TA97a strains, while the clastogenic effect in Chinese hamster ovary (CHO) cells
      in the G(1)/S, S and G(2)/S phases of the cell cycle. The results showed
      mutagenic activity of the aqueous extract against TA102 in the presence of S9,
      and of methanolic extract, with and without metabolic activation. TA100
      mutagenicity was only observed for the methanolic extract in the absence of S9.
      The n-butanolic fraction did not present mutagenic activity. In CHO cells only
      the methanolic extract induced a significant increase of chromosomal aberrations
      in the G(1)/S and S phases, whereas a decrease in the mitotic index was observed
      in the G(1)/S and G(2)/S phases. No clastogenicity was observed for the aqueous
      extract. The furocoumarins (psoralen and bergapten) presented in the extracts
      might contribute to the mutagenicity. The lower activity of the aqueous extract
      was probably due to the presence of smaller amount of furocoumarins compared to
      the methanolic extract.

PMID- 12065161
TI  - Fetal toxicity of Solanum lycocarpum (Solanaceae) in rats.
AB  - Lobeira (Solanum lycocarpum) is a Brazilian plant used as a hypoglycemic agent.
      In this study, the toxic effects of lobeira were evaluated during the fetogenesis
      period. Twenty pregnant Wistar rats were randomly allocated into two groups:
      control and treated, which received, via oral gavage, 0.5 ml of distilled water
      or 100 mg of the lobeira powder/kg of body weight, respectively, during days 17
      20 of pregnancy. Maternal toxicity was evaluated by body weight, food intake,
      piloerection, locomotor activity, diarrhoea and vaginal bleeding. Euthanasia was
      done on 21st day, when ovaries, fetuses and their respective placentas were
      removed. Resorptions, live and dead fetuses were recorded. External malformations
      and fetal body, brain, liver, lung and kidneys were also weighed. No clinical
      signs of maternal toxicity were observed. The placenta weights of the treated
      rats were lower than those of the control (P<0.01). Lungs (P<0.01) and kidneys
      (P<0.02) of the fetuses treated with lobeira were also significantly reduced,
      suggesting a fetotoxic effect of this plant.

PMID- 12065163
TI  - Antithrombin activity of medicinal plants from central Florida.
AB  - A chromogenic bioassay was utilized to determine the antithrombin activity of
      methylene chloride and methanol extracts prepared from 30 plants of central
      Florida. Extracts of Ardisia crenata, Tetrapanax papyriferus, Lagerstroemia
      indica, Callistemon lanceolatus, Antigonon Leptopus, Magnolia virginiana, and
      Myrica cerifera demonstrated activity of 80% or higher in this bioassay system.

PMID- 12065162
TI  - Anti-inflammatory activity of two different extracts of Uncaria tomentosa
      (Rubiaceae).
AB  - We assessed in vivo the anti-inflammatory activity of two Cat's claw bark
      extracts, by comparing a spray-dried hydroalcoholic extract against an aqueous
      freeze-dried extract, to determine which extract was more effective. We used the
      carrageenan-induced paw edema model in mice. In addition, to assess the molecular
      mechanism of action, we determined the inhibition of NF-kappa B through the
      Electrophoretic Mobility Shift Assay (EMSA) and the effects on cycloxygenase-1
      and -2. Results showed that the anti-inflammatory activity was significantly
      higher using the hydroalcoholic compared with the aqueous extract (P<0.05). The
      extracts also showed little inhibitory activity on cyclooxygenase-1 and -2. It
      cannot be excluded that the slight inhibitory activity on DNA binding of NF-kappa
      B is due to cytotoxic effects.

PMID- 12065164
TI  - Relative efficacy of three medicinal plant extracts in the alteration of thyroid
      hormone concentrations in male mice.
AB  - Relative importance of Bacopa monnieri (200 mg/kg), Aegle marmelos (1.00 g/kg)
      and Aloe vera (125 mg/kg) leaf extracts in the regulation of thyroid hormone
      concentrations in male mice was investigated. While serum levels of both T(3) and
      T(4) were inhibited by A. vera, A. marmelos extract could decrease only T(3)
      concentration. On the other hand, T(4) concentration was increased by B. monnieri
      extract suggesting its thyroid-stimulating role. When the relative potency of
      each plant extract was calculated in terms of percent increase or decrease in
      thyroid hormones, as compared to the control value, the decrease in T(3)
      concentration by A. marmelos was about 62% indicating its possible use in the
      regulation of hyperthyroidism. B. monnieri could increase T(4) concentration by
      41% without enhancing hepatic lipid peroxidation (LPO) suggesting that it can be
      used as a thyroid-stimulating drug. In fact, hepatic LPO was decreased and
      superoxide dismutase (SOD) and catalase (CAT) activities were increased by B.
      monnieri and A. marmelos leaf extracts showing their antiperoxidative role. It is
      thus suggested that A. marmelos and A. vera may be used in the regulation of
      hyperthyroidism, while B. monnieri in hypothyroidism.

PMID- 12065165
TI  - Antimicrobial studies on three species of Hypericum from the Canary Islands.
AB  - The antimicrobial activity of several extracts and fractions of the aerial parts
      of Hypericum canariense, Hypericum glandulosum and Hypericum grandifolium was
      investigated using the disc diffusion and broth microdilution methods against
      twelve reference microorganisms (eight bacterial and four fungal strains). The
      methanol extract and chloroform fraction of H. canariense, as well as the
      methanol extracts, butanol and chloroform fractions of both H. glandulosum and H.
      grandifolium exhibited a good antibacterial activity against four Gram-positive
      bacteria (Bacillus cereus var. mycoides, Micrococcus luteus, Staphylococcus
      aureus and Staphylococcus epidermidis) and the Gram-negative bacterium Bordetella
      bronchiseptica with the diameters of growth inhibition area in the range 10-25 mm
      and MICs values between 0.03 and 0.29 mg/ml. Neither the infusions and aqueous
      fractions of the species studied nor the butanol fraction of H. canariense showed
      any antibacterial activity against the tested microorganisms. Amongst the active
      extracts, the minimum inhibitory concentration (MIC) determination showed that
      the H. canariense chloroform fraction was the most active against M. luteus, S.
      aureus and S. epidermidis. No antifungal activity was seen with any of the
      extracts or fractions tested. The results of this study support the use of these
      species in Canarian traditional medicine to treat skin infections.

PMID- 12065166
TI  - Antimicrobial diterpenoids from Eupatorium glutinosum (Asteraceae).
AB  - The antimicrobial properties of the hexane extract from the leaves and twigs of
      the Eupatorium glutinosum was tested against two Gram-negative and two Gram
      positive bacteria. Bioassay guided fractionation leads characteristically to
      isolation and structure elucidation of two active compounds: 15-hydroxy-7-labden
      17-oic acid and its acetate. These results validate the vernacular medicinal uses
      of the plant in folkloric medicine. Dammara-20, 24-dien-3-acetate, stigmasterol
      and epi-friedelanone have been also isolated in addition to the palmitate of
      nepehinol for the first time as naturally occurring.

PMID- 12065168
TI  - Endometrial safety of hormone replacement therapy: review of literature.
AB  - Unopposed estrogens for treating menopausal symptoms were extensively used when
      epidemiological findings associated them with an increased endometrial cancer
      risk. Adding progestogens reverse this side effect efficiently but patient, dose,
      type and especially time during which the progestogen is administered are
      important. Long-term uterine safety of the long cycle HRT with administration of
      the progestogen every 3 months remains unclear. Because regular bleeding lowers
      compliance, continuous combined estrogen-progestogen treatment has become
      popular. Many different regimens are now available using oral, transdermal,
      subcutaneous, intravaginal or intra-uterine application of the estrogen and/or
      progestogen. Available but inadequate studies seem to point towards a slightly
      decreased endometrial cancer risk with continuous combined preparations compared
      with non-HRT-users and an increased risk with long-term oral but not vaginal
      treatment with low-potency estrogen formulations such as estriol. Newer compounds
      for menopausal health such as tibolone and raloxifene seem to be safe. As for any
      women with abnormal vaginal bleeding, those on HRT must have an intra-uterine
      evaluation. Transvaginal ultrasound (TVU) is very accurate in predicting a normal
      uterine cavity but inaccurate in predicting endometrial pathology because of a
      low specificity and positive predictive value of a thick echogenic endometrium.
      In all such cases a three-dimensional visualisation of intra-uterine lesions is
      more accurate. Periodic examination with TVU and/or endometrial biopsy of HRT
      exposed endometrium in asymptomatic women is not cost-effective. The available
      limited data on the use of HRT in hysterectomised women for early stage
      endometrial cancer show little evidence in terms of recurrence.

PMID- 12065169
TI  - Risk of low bone density in women attending menopause clinics in Italy.
AB  - OBJECTIVE: In order to offer data on the epidemiological profile of women with
      low bone density (LBD), we have considered information collected in the framework
      of a large cross-sectional study conducted on women around menopause attending a
      network of first level outpatients menopause clinics in Italy. METHODS: During
      1997 and 2000, a large cross sectional study was conducted on the characteristics
      of women around menopause attending a network of first level outpatients
      menopause clinics in Italy for general counseling about menopause or treatment of
      menopausal symptoms. Eligible for the study were women consecutively observed
      during the study period. Up to March 2000 a total of 42464 women (mean age 53
      years) were observed at the 268 participating centers. Bone mass density was
      measured in 25113 cases, which are considered in this analysis. LBD (i.e.
      osteopenia or osteoporosis) was defined according to WHO classification. RESULTS:
      The frequency of LBD increased with age: in comparison with women aged < or =51
      years, the odds ratio (OR) of LBD was 1.5 and 2.2, respectively, in women aged 52
      55 and > or =56. No association emerged between LBD and parity: in comparison
      with nulliparae, the OR of LBD were 1.1 and 1.0, respectively, in women reported
      1 or 2 or more full term pregnancies. Smokers were at increased risk of LBD, the
      corresponding OR being for smokers, in comparison with non smokers, 1.2 (95%
      confidence interval, CI, 1.1-1.3). In comparison with women in the lower tertile
      of body mass index, the OR of LBD decreased in subsequent tertiles, being,
      respectively, 0.9 and 0.7 in the middle and highest tertile. The OR of LBD was
      2.2 in postmenopausal women, in comparison with premenopausal ones and the OR
      decreased increasing age at menopause. Ever OC users were at slightly decreased
      risk of LBD: in comparison with never OC users, the OR was 0.9 (95% CI 0.8-1.0)
      in ever OC users. CONCLUSION: The results of this large study confirm, in a
      Southern European population, the association of age at menopause and body mass
      on the risk of LBD, and suggest that ever OC women are at decreased risk of LBD.

PMID- 12065171
TI  - Relationship between estrogen use and musculoskeletal function in postmenopausal
      women.
AB  - OBJECTIVES: The purpose of this study was to examine the relationship between
      estrogen use and muscle strength, bone mineral density (BMD), and body
      composition variables in postmenopausal women. Forty healthy, untrained women
      participated in this study. Subjects (53-65 years) were > or =5 years
      postmenopausal and were categorized into either estrogen replacement therapy (ERT
      n=20) or non-estrogen replacement therapy (Non-ERT n=20) groups. METHODS:
      Muscular strength was measured by 1-RM testing using Cybex isotonic weight
      machines. Handgrip strength was measured using a handgrip dynamometer. Diagnostic
      Ultrasound was used to determine cross-sectional areas of the biceps brachii and
      rectus femoris muscle groups. BMD of the lumbar spine, proximal femur, and total
      body was assessed by Dual Energy X-Ray Absorptiometry (Lunar DPX-IQ). Body
      composition variables were obtained from the total body scan. Serum osteocalcin
      was measured as an indicator of bone remodeling. RESULTS: There were no
      significant differences (P>0.05) for isotonic muscular strength, muscle cross
      sectional areas, handgrip strength, or percent fat between ERT and Non-ERT
      groups. ERT had significantly higher (P<0.05) BMD for the total body, femoral
      neck and Ward's Area. There were moderate positive relationships between lean
      body mass and the hip sites (r=0.61-0.70, P<0.05). Regression analyses determined
      that lean body mass was the strongest predictor of the hip BMD sites. Estrogen
      use also was a significant predictor for the femoral neck and Ward's Area sites.
      CONCLUSION: Women taking estrogen exhibited similar muscular strength, muscle
      size, and body composition as their estrogen-deficient counterparts. Estrogen use
      was also associated with higher BMD for the total body and hip sites. Generally,
      body composition, specifically lean body mass, influenced hip BMD more than
      muscular strength or estrogen use.

PMID- 12065170
TI  - Role of DEXA and ultrasonometry in the evaluation of osteoporotic risk in
      postmenopausal women.
AB  - BACKGROUND/AIM: The aim of this study was to compare the role of quantitative
      ultrasonography (QUS) and dual energy X-ray absorptiometry (DEXA) in the
      assessment of osteoporosis. METHODS: From June 1999 to November 2001, 596 women
      who have not been diagnosed osteoporosis and without previous history of
      pathologic fractures were enrolled in this study. They had a mean age of 58.7+/
      8.5 years, a mean height of 166+/-3.5 cm and a mean weight of 66+/-4.1 kg.
      According to the age, women were divided into three groups: group A included
      women between 45 and 55 years; group B women between 56 and 66 years and group C
      women between 67 and 77 years. Each patient underwent to both methods to
      determine the presence of osteoporosis. RESULTS: QUS resulted in a greater number
      of women of group A at risk of osteoporosis, whereas DEXA indicated that more
      women of group C were at increased osteoporotic risk. QUS and DEXA gave
      concordant results only in women of group B. CONCLUSION: These results suggested
      that QUS screening for osteoporosis may be more suitable for 'younger'
      postmenopausal women.

PMID- 12065172
TI  - Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone
      replacement therapy.
AB  - OBJECTIVES: To study the possible interaction between ascorbic acid (AA) and
      oestradiol (E2) in postmenopausal women on hormone replacement therapy (HRT).
      METHODS: We studied 25 healthy postmenopausal women who had used percutaneous E2
      gel at same dose for 10-12 months, at which time the plasma E2 concentrations
      were stabilized. The subjects were treated with 1000 mg of AA daily for 3 months
      and blood samples for assay of AA and E2 were taken at 0, 1 and 3 months.
      RESULTS: After 1 month of AA treatment, there was an overall increase of 20.8% in
      E2 levels in the group as a whole. Greater responses were seen in two subgroups.
      In women with initially the lowest plasma concentrations of AA (<70 micromol/l),
      there was an increase of 55% in plasma E2 levels which was close to significance
      (P=0.063). In another subgroup with initially the lowest E2 levels (<0.20 nmol/l)
      there was a marked and significant increase (from 0.13 to 0.26 nmol/l) in plasma
      E2 concentrations (P=0.028). CONCLUSIONS: Our results support early findings that
      AA may interact with oestrogen therapy. Possible interaction of AA with E2 at the
      level of antioxidation is discussed.

PMID- 12065173
TI  - Efficacy and safety of oral and transdermal hormonal replacement treatment
      containing levonorgestrel.
AB  - OBJECTIVES: The oral combined formulation of levonorgestrel with estradiol
      valerate (LNG+EV) has demonstrated to be effective on some postmenopausal
      symptoms. The availability of a transdermal HRT in sequential formulation with 17
      beta-estradiol plus levonorgestrel (TSE2+TSLNG) induced us to do this control
      study with the aim to evaluate the efficacy and safety of both oral and
      transdermal treatments. METHODS: At baseline, the psychological symptoms with the
      psychometric scale SCL-90, the bone resorption with the measurement of the
      urinary levels of pyridinoline and dexoxypirydinoline, and the insulin and lipid
      metabolism were assessed in 30 postmenopausal women (PMW) and in 18 premenopausal
      women. Then, the PMW women were randomly divided in three groups: group A (N=10)
      assumed EV+LNG, group B (N=10) did not assume any treatment, group C (N=10) was
      treated with TSE2+TSLNG. The length of the study was 12 months. The
      aforementioned assessments were repeated at different time-intervals up to the
      end of the study. RESULTS: The total score of SCL-90, the bone resorption, the
      levels of LDL-cholesterol, total-cholesterol and the parameters of insulin
      metabolism were higher in PMW than in premenopausal women. During the study, the
      SCL-90, the bone resorption, total-cholesterol, and LDL-cholesterol levels
      significantly decreased only in the groups A and C. By contrast, in the group B
      bone resorption significantly increased at the 12th month. During the treatments,
      insulin metabolism did not change in the groups A and B. In the group C the
      secretion of C-peptide and the C-peptide:insulin ratio after OGTT were
      significantly higher at the 12th month than before treatment. In all groups the
      endometrium thickness did not change during the study. CONCLUSION: A 12-month of
      either oral or transdermal HRT containing levonorgestrel seems to exert
      beneficial effects on the main postmenopausal symptoms without negative
      interferences on the endometrium.

PMID- 12065174
TI  - The effects of oral estriol on the endometrium in postmenopausal women.
AB  - OBJECTIVES: To study the long-term effects of oral estriol tablets on the
      endometrium of postmenopausal women by TVS and histology. METHOD: This was a
      cross sectional, parallel-group, multicenter trial of 241 postmenopausal women,
      out of whom 125 were treated with oral estriol and 116 were untreated controls.
      Endometrial histology using Pipelle biopsies and/or dilatation and curettage
      (D&C) was taken, endometrial thickness was assessed by use of transvaginal
      ultrasound (TVS), and the relation between endometrial thickness and histology
      was calculated. RESULTS: No statistically significant differences between the two
      groups were found in endometrial histology. There were found more polyps in the
      oral estriol group (14.0%) as compared with the control group (2.9%). The mean
      endometrial thickness in the oral estriol group was 3.0 mm compared with a mean
      value of 2.4 mm in the control group: P=0.01. CONCLUSIONS: No clinically relevant
      difference was found between the endometrium status (assessed by histology and
      TVS) of postmenopausal women on long-term oral estriol therapy and untreated
      controls. This trial supports the endometrial safety of maintenance treatment
      with oral estriol tablets. However, there are signs, not statistically
      significant, that may be associated with more endometrial polyps in
      postmenopausal women than if therapy is not given and that TVS is a useful
      instrument for the diagnosis.

PMID- 12065175
TI  - Combined oral estradiol valerate-norethisterone treatment over 3 years in
      postmenopausal women: effect on lipids, coagulation factors, haematology and
      biochemistry.
AB  - OBJECTIVE: To determine the effect of continuous estradiol valerate 2 mg and
      norethisterone 0.7 mg daily as hormone replacement on lipid profiles, coagulation
      factors, haematology and biochemistry over 3 years. METHODS: An open label trial
      with 107-133 postmenopausal women assessed pre-treatment and at annual visits
      with extensive lipid and coagulation profiles, and observation of circulatory
      adverse events. Standard haematology and biochemical profiles were also analysed.
      Results were compared at point of entry and at 36 months. RESULTS: Total
      cholesterol (TC) and HDL and LDL fractions fell significantly (P=0.0001) and
      there was a significant decline in favourable ratios as well as a rise in VLDL
      mass (P=0.0001). Lipoprotein (a) (Lp(a)) decreased significantly (P=0.0053).
      Fibrinogen, free protein, prothrombin time and thrombin increased (P=0.0001)
      while platelets and KPTT were unchanged. Protein C, antithrombin III and total
      protein S decreased (P=0.0001) and there was a rise in the frequency of lupus
      anticoagulant positivity. Significant but small changes were seen in haematology
      and biochemical parameters although this did not raise safety issues and their
      clinical significance was uncertain. CONCLUSION: The direction of lipid and
      coagulation factors move in competing ways, emphasising the complexity of
      metabolic change and making interpretation of outcome for venous and arterial
      thrombosis or atherosclerosis difficult to predict. Eight patients developed
      thromboembolic or ischaemic events over the 3 year period of this study but these
      patients had lipid changes normally considered beneficial to cardiovascular
      disease and coagulation changes not thought to be associated with
      thromboembolism. Decrease in lipoprotein 'a' levels might be an indicator of long
      term decreases in atherosclerotic events.

PMID- 12065176
TI  - Behavioural and neurocognitive implications of snoring and obstructive sleep
      apnoea in children: facts and theory.
AB  - The pathophysiology of obstructive sleep apnoea (OSA), a common condition in
      children, is poorly understood. While adenotonsillar hypertrophy is certainly a
      major contributor, other factors are needed for OSA to develop. OSA has been
      associated with substantial morbidities primarily affecting cardiovascular and
      neurobehavioural systems which may not be completely reversed with appropriate
      treatment. This paper reviews the available information and attempts to provide
      the rationale for early diagnosis and treatment of OSA in children.

PMID- 12065177
TI  - Home monitoring during infancy: what is normal?
AB  - This article reviews studies on infants to obtain 'normal' parameters for apnoea,
      heart rate and O(2) saturation in healthy full-term infants. Studies have been
      carried out in both hospital and home settings using different protocols and
      these are reviewed and assessed as a means of providing baseline data for home
      memory monitoring of infants.

PMID- 12065178
TI  - Diagnostic techniques for obstructive sleep apnoea: is polysomnography necessary?
AB  - Obstructive sleep apnoea (OSA) is a common condition of childhood with
      significant associated morbidity. The comprehensive evaluation of children who
      present with suggestive symptoms involves the overnight recording and assessment
      of both sleep and respiration by polysomnography in a sleep laboratory. These
      studies require resources and facilities that are not widely available and thus
      simpler, more available and less expensive alternatives have been sought. This
      review discusses the available alternatives to polysomnography for the evaluation
      of the child with suspected obstructive sleep apnoea.

PMID- 12065179
TI  - Surgical strategies in the treatment of complex obstructive sleep apnoea in
      children.
AB  - Complex OSA in children is a challenging problem that requires careful team
      management. Evaluation includes history, physical examination and appropriate
      radiological and endoscopic studies. Twelve-channel polysomnography, with or
      without a pH probe, is mandatory in children with OSA to determine the severity
      and to document the efficacy of treatment. A variety of individual problems and
      nuances arise and will continue to do so. Clinical experience and a high degree
      of suspicion in the craniofacial population is necessary to rule out the
      existence of OSA in a given patient. Newer treatment modalities, such as
      distraction osteogenesis of the mandible and midface, have revolutionised
      treatment of OSA during childhood. Although still the gold standard of care,
      tracheostomy is not a benign procedure and the toll on both the patient and
      family can be devastating.

PMID- 12065180
TI  - Stem cells of the respiratory tract.
AB  - Childhood respiratory diseases are accompanied by various forms of epithelial
      repair and remodelling. Respiratory stem cells are likely to be of great
      importance in these processes but their identification remains uncertain. By
      contrast, an enormous effort has been made to identify specific markers of stem
      cells of other organs; this has given rise to the new concept of plasticity. This
      proposes that stem cell differentiation is influenced by the niches in which the
      cells reside rather than their site of origin. Many studies provide evidence in
      support of this concept, including one demonstrating that respiratory epithelium
      can arise from bone marrow stem cells. Recent findings from human and animal
      studies suggest that Clara cell-specific protein-expressing cells with pre-Clara
      cell phenotypes may be candidate stem cells for the entire respiratory tract.

PMID- 12065181
TI  - Cellular network in airways inflammation and remodelling.
AB  - Chronic inflammation and airway remodelling are two key steps in asthma
      pathophysiology. The development of chronic airway inflammation depends upon the
      continuous recruitment of inflammatory cells from the bloodstream towards the
      bronchial mucosa and by their subsequent functional activation. The release of
      inflammatory mediators by activated cells contributes to the generation of a
      complex network which involves mobile inflammatory cells and structural cells
      such as epithelial cells, fibroblasts and myofibroblasts. This network is
      responsible for the amplification and persistence of the inflammatory process as
      well as for the development of a peculiar microenvironment which can directly
      modulate the survival of inflammatory cells in the inflamed airways. Increased
      cellular recruitment and activation, enhanced cell survival and cell:cell
      interactions are therefore the key steps in the development of chronic airway
      inflammation in asthma and represent the major causes for tissue damage, repair
      and remodelling.

PMID- 12065182
TI  - Genetics of asthma and related phenotypes.
AB  - Asthma is the most common chronic childhood disease in developed nations. It has
      been clearly shown that several environmental, as well as genetic, factors play
      an important role in the development of this complex disease. In the last decade
      many genome-wide screens have been performed to specify the chromosomal
      localisation of the genes of interest. Simultaneously more than a hundred
      candidate gene studies have been published. The results between the different
      studies often vary. To date no major gene for asthma has been detected. Therefore
      more extensive genetic approaches will be necessary in the future.

PMID- 12065183
TI  - The role of clinical practice guidelines in enhancing quality and reducing
      racial/ethnic disparities in paediatrics.
AB  - Paediatricians believe that clinical practice guidelines (CPGs) can improve
      patient care but only when the CPGs are flexible, rigorously tested, effective,
      not used punitively and are motivated by desires to improve quality, not reduce
      costs. Paediatricians may avoid using CPGs because few have been subjected to
      rigorous evaluation to demonstrate improved quality and reduced costs. Effective
      physician adherence to a CPG can be viewed as a multi-step process with potential
      barriers at each step. Barriers to adherence can be classified as internal (lack
      of awareness, familiarity, agreement, self-efficacy, outcome expectancy regarding
      a given CPG and inability to overcome the inertia of current practice) or
      external (deficits in the required CPG implementation infrastructure). Effective
      interventions for overcoming barriers to CPG adherence can include multiple modes
      of disseminating CPG information to practitioners, continuing medical education,
      feedback to physicians and establishing a solid infrastructure for CPG
      implementation. Adherence to evidence-based asthma CPGs may be a potentially
      powerful tool for reducing or eliminating racial/ethnic disparities in asthma
      treatment because CPGs consist of strict, explicit protocols based on symptoms,
      not race, ethnicity or socioeconomic status.

PMID- 12065184
TI  - Chest imaging in the immunocompromised child.
AB  - The immunodeficiency states in children may be sub-divided into two major groups;
      congenital (primary), and acquired (secondary). The spectrum of illness and
      imaging appearances are similar, regardless of the underlying cause of
      immunodeficiency. All immunodeficiency states are associated with an increased
      susceptibility to infection and neoplasia, with the lymphoproliferative disorders
      being the most frequent. However, the type of infections encountered and the
      risks of neoplasia are influenced by the underlying defect (whether predominantly
      humoral or cell mediated), the use of immunosuppressive drugs or radiotherapy as
      well as the length of immunosuppression.A working knowledge of the underlying
      likely immune defect is therefore important when interpreting imaging findings in
      children with immunodeficiency states. The typical imaging appearances of the
      common infectious, non-infectious and neoplastic complications of
      immunodeficiency are described.

PMID- 12065185
TI  - Perinatal corticosteroids and the developing lung.
AB  - A significant number of infants are born prematurely each year, many of whom will
      develop respiratory disease and require ventilation. A substantial number of
      these infants will die and many of the survivors will subsequently develop
      chronic inflammatory lung disease. Administration of corticosteroids to women
      prior to a premature delivery is associated with a significant reduction in
      mortality and in the incidence of respiratory distress syndrome and intracranial
      haemorrhage in their infants once born. Postnatal administration of
      corticosteroids to the infant who develops chronic lung disease has been widely
      practised for many years. Recent meta-analyses have suggested that benefit may be
      limited. Treatment is also associated with a range of different side-effects but
      it has been assumed that the cost-benefit ratio favoured treatment. Recent
      evidence of permanent and highly significant long-term adverse effects has
      questioned the validity of this judgement.

PMID- 12065186
TI  - The pancreas in cystic fibrosis.
AB  - The pancreas secretes a bicarbonate-rich fluid containing digestive enzymes via
      the ampulla of Vater into the duodenum. Defective secretion leads to maldigestion
      of fat and protein with increased faecal losses. Cystic fibrosis (CF) is the
      major cause of pancreatic exocrine failure in childhood, whereas pancreatic
      insufficiency in adults is commonly associated with chronic pancreatitis and
      alcohol ingestion. In cystic fibrosis, pancreatic function correlates with
      genotype; pancreatic-sufficient (PS) patients have a milder course of respiratory
      disease, improved survival and lower mean sweat chloride concentrations than
      those with pancreatic insufficiency. Recent observations suggest that mutant CF
      alleles are over-represented in patients with chronic pancreatitis. Few show
      evidence of sino-pulmonary disease or high sweat electrolyte concentrations.

PMID- 12065188
TI  - Beta-adrenoceptor agonists and asthma--100 years of development.
AB  - Inhaled beta(2)-adrenoceptor agonists are by far the most effective and safe
      bronchodilators currently available. They have not been surpassed by any other
      bronchodilating principle. The way to this position has been long and started
      with the first successful treatment of acute, severe asthma with s.c. injections
      of adrenaline 100 years ago. Over the years, synthetic congeners of adrenaline
      have been produced and tested for their pharmacological properties. During the
      first decades, little attention was given airway smooth muscle. The discovery of
      isoprenaline in 1940 was the first major step towards selective bronchodilation.
      This compound became a key tool for the classification of adrenoceptors into
      alpha and beta. Salbutamol and terbutaline were the first to show a significant
      attenuation of the cardiostimulant effect and confirmed the subdivision of beta
      adrenoceptors into beta(1) and beta(2). Much effort was made to eliminate the
      next dose-limiting side effect, skeletal muscle tremor but in vain. Prolonged
      duration of action was achieved in three ways: with bambuterol, an orally active
      carbamate ester prodrug of terbutaline, salmeterol, an inhaled beta(2)
      adrenoceptor agonist emerging from a purposeful research project, and formoterol
      which was found, accidentally, to have a long duration of action when inhaled.
      Throughout the 20th century, beta-adrenoceptor agonists have been developed and
      marketed as racemates. The pharmacological activity usually resides in the (R)
      enantiomer. Despite claims for the opposite, there is so far no compelling
      evidence that the presence of the less active (S)-enantiomer is of any harm to
      the patient. One hundred years of experience of structural modifications of
      adrenaline has shown that the possibilities to modify the properties of this
      endogenous prototype appear to be unlimited.

PMID- 12065187
TI  - Decisions facing the cystic fibrosis clinician at first isolation of Pseudomonas
      aeruginosa.
AB  - Chronic endobronchial infection with shape Pseudomonas aeruginosa in patients
      with cystic fibrosis is associated with more serious disease and reduced
      survival. Methods for reducing or preventing chronic infection with P. aeruginosa
      involve rigorous infection control measures and avoidance of cross-infection,
      which may include segregation of clinics according to microbiological status. The
      strains of shape P. aeruginosa first isolated from the lungs of cystic fibrosis
      patients are generally of a non-mucoid phenotype and sensitive to antibiotic
      therapy. There is some evidence that early aggressive antibiotic treatment may
      delay chronic infection, improve lung function and improve survival. Further
      research is needed into the accurate diagnosis of early infection with shape P.
      aeruginosa, which is often intermittent. In addition, the optimal treatment of
      patients at first isolation and early colonisation needs to be researched,
      including choice of antibiotic(s) and route, dosage and duration of antibiotic
      therapy.

PMID- 12065189
TI  - Studies on the role of calcium in the 5-HT-stimulated release of glutamate from
      C6 glioma cells.
AB  - We recently reported that 5-hydroxytryptamine(2A) (5-HT(2A)) receptor activation
      on cultured glial cells induces glutamate release [J. Neurosci. Res. 67 (2002)
      399]. Here we use C6 glioma cells to examine the role of calcium in this
      response. 5-Hydroxytryptamine (5-HT) increases glutamate release from C6 glioma
      cells, an effect blocked by low calcium conditions. The calcium ionophores
      ionomycin and calcimycin also released glutamate from C6 glioma cells in a Ca(2+)
      dependent manner. The effect of 5-HT was reduced by the phospholipase C inhibitor
      U73122 (1-[6[[(17 beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H
      pyrrole-2,5-dione), but not its inactive enantomer U73343(1-[6[[(17 beta)-3
      methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione). The
      protein kinase C inhibitors staurosporine and calphostin C had no effect on the
      response to 5-HT, whereas the response was blocked by thapsigargin and caffeine.
      Neither the L-type calcium channel blockers, nifedipine and verapamil, nor the N
      type calcium channel blocker omega-conotoxin GVIA inhibited the effect of 5-HT,
      whereas NiCl(2) and KCl blocked the response to 5-HT. We conclude that the 5-HT
      induced efflux of glutamate from C6 glioma cells is Ca(2+)-dependent and
      involves, at least in part, the mobilisation of Ca(2+) from inositol (1,4,5) tris
      phosphate (IP(3)) sensitive intracellular stores.

PMID- 12065190
TI  - (+/-)-Domesticine, a novel and selective alpha1D-adrenoceptor antagonist in
      animal tissues and human alpha 1-adrenoceptors.
AB  - The pharmacological profile of (+/-)-domesticine, a novel alpha(1)-adrenoceptor
      antagonist, was examined in animal tissues and Chinese hamster ovary (CHO) cells
      expressing cloned human alpha(1)-adrenoceptor subtypes and compared with the
      properties of BMY-7378 ([8-(2-[4-(2-methoxy-phenyl)-1-piperazinyl]ethyl)-8
      azaspirol [4.5]decane-7,9-dione dihydrochloride], the prototypical alpha(1D)
      adrenoceptor antagonist. Both (+/-)-domesticine and BMY-7378 were more potent in
      inhibiting the phenylephrine-induced contraction in rat thoracic aorta than tail
      artery or spleen. The selectivity of (+/-)-domesticine to inhibit phenylephrine
      induced contraction in rat thoracic aorta was 32- and 17-fold higher than that in
      tail artery and spleen, respectively, while that of BMY-7378 it was 125- and 11
      fold, respectively. The functional affinity profiles of these compounds for the
      alpha(1)-adrenoceptor subtypes in animal tissues were consistent with the
      respective binding affinity profiles in cloned human alpha(1)-adrenoceptor
      subtypes. (+/-)-Domesticine displayed a 34- and 9-fold higher selectivity for
      alpha(1d)-adrenoceptor than for alpha(1a)- and alpha(1b)-adrenoceptor,
      respectively, while BMY-7378 showed a selectivity for alpha(1d)-adrenoceptor of
      102-fold higher than that of alpha(1a)-adrenoceptor and 21-fold higher than that
      of alpha(1b)-adrenoceptor. Interestingly, in [3H]8-OH-DPAT (8-hidroxy-2-(di-n
      propyl-amino)tetraline hidrobromide) binding to 5-HT(1A) receptors of rat
      cerebral cortex, (+/-)-domesticine showed a 183-fold higher selectivity for
      alpha(1D)-adrenoceptor relative to 5-HT(1A) receptor, whereas BMY-7378 displayed
      a similar affinity at this receptor with respect to the alpha(1D)-adrenoceptor
      (0.89-fold). Both compounds, however, showed a weak affinity for 5-HT(2A)/5
      HT(2C) receptors in rat frontal cortex. These results suggest that (+/-)
      domesticine is more potent for alpha(1D)-adrenoceptor than for alpha(1A)- or
      alpha(1B)-adrenoceptor subtypes and it is highly selective compared to 5-HT(1A)
      and other receptors.

PMID- 12065191
TI  - The nonadrenergic noncholinergic relaxation of anococcygeus muscles of bile duct
      ligated rats.
AB  - Previous studies have shown the naloxone-induced withdrawal syndrome and the
      development of tolerance in the tissues of cholestatic animals. Increased
      neuronal nitric oxide synthase (nNOS) expression is reported to exist in morphine
      tolerant animals. This, together with evidence for nitric oxide (NO)
      overproduction in cholestasis, suggested the possibility of an alteration of
      nonadrenergic noncholinergic (NANC) relaxation of anococcygeus muscles of
      cholestatic rats. To study this, we used three main groups of animals:
      unoperated, sham-operated and bile duct-ligated. Electrical field stimulation, in
      the presence of atropine and guanethidine, caused NANC relaxation in the
      anococcygeus muscle which was enhanced in bile duct-ligated animals. N(G)-nitro-L
      arginine methyl ester (L-NAME), a NOS blocker, caused a dose-dependent inhibition
      of the NANC relaxation. The IC(50)'s of L-NAME in 7-day (7.30+/-0.87 microM), 14
      day (6.98+/-0.70 microM) and 21-day (8.25+/-1.40 microM) bile duct-ligated groups
      were significantly different from those of unoperated (1.69+/-0.30 microM) and
      sham-operated groups (1.90+/-0.27 microM). L-NAME (100 microM) completely
      inhibited the NANC relaxation response, suggesting that NANC relaxation in the
      rat anococcygeus muscle is mediated mainly via NO. The contraction response of
      the intact muscle to phenylephrine, an alpha(1)-adrenoceptor agonist, and the
      relaxation response of the phenylephrine-contracted muscle to sodium
      nitroprusside, an NO donor, were not different in unoperated, sham-operated and 7
      day bile duct-ligated groups. These results showed that the smooth muscle
      component of NANC relaxation is not altered in anococcygeus muscles of bile duct
      ligated rats. It can thus be concluded that the NANC relaxation in the
      anococcygeus of cholestatic rats is more resistant to a NOS blocker, providing
      evidence for increased nitrergic neurotransmission in the anococcygeus muscles of
      cholestatic rats.

PMID- 12065192
TI  - The interaction between the locus coeruleus and dorsal raphe nucleus studied with
      dual-probe microdialysis.
AB  - The interaction between the locus coeruleus and dorsal raphe nucleus was
      investigated by means of dual-probe microdialysis in conscious rats. The release
      of noradrenaline and 5-hydroxytryptamine (5-HT) after inhibition or stimulation
      of locus coeruleus and dorsal raphe activity was sampled in both nuclei and
      analysed by high-pressure liquid chromatography (HPLC). The inhibition of locus
      coeruleus activity by the infusion of the alpha(2)-adrenoceptor agonist clonidine
      (100 microM) decreased the release of noradrenaline to 20% in the locus coeruleus
      and 30% in the dorsal raphe, whilst the release of 5-HT decreased to 80% of
      control in the two brain areas. The excitation of locus coeruleus activity by the
      muscarinic receptor agonist carbachol (100 microM) led to an increase in the
      release of noradrenaline to 240% and 220% of control in the locus coeruleus and
      dorsal raphe, respectively. The release of 5-HT in both nuclei did not respond to
      the carbachol infusion into the locus coeruleus. Infusion of the 5-HT(1A)
      receptor agonist flesinoxan into the dorsal raphe (1 microM) significantly
      decreased the release of 5-HT in the dorsal raphe and locus coeruleus to 45% and
      65% of control, respectively. The release of noradrenaline was decreased in the
      dorsal raphe to 45% by flesinoxan, whereas no changes were seen in the release of
      noradrenaline in the locus coeruleus. In conclusion, the innervation of the
      dorsal raphe by the locus coeruleus has a slight excitatory effect on the release
      of 5-HT in the dorsal raphe. The dorsal raphe does not exert a direct inhibitory
      influence on the release of noradrenaline in the locus coeruleus. Finally, the
      release of noradrenaline in the dorsal raphe may be locally regulated by 5-HT(1A)
      receptors.

PMID- 12065193
TI  - Pharmacokinetic-pharmacodynamic modelling of the hypothermic and corticosterone
      effects of the 5-HT1A receptor agonist flesinoxan.
AB  - The current investigation describes the pharmacokinetic-pharmacodynamic
      correlation of the hypothermic and the corticosterone effect of flesinoxan in the
      rat simultaneously. A specific objective was to determine the influence of
      handling the animal. The pharmacokinetic-pharmacodynamic correlation was
      determined following intravenous administration of 3 and 10 mg/kg flesinoxan in 5
      or 15 min. Serial blood samples were obtained for determination of the time
      course of the flesinoxan and corticosterone concentrations by high performance
      liquid chromatography. Body temperature was monitored using a telemetric probe.
      The pharmacokinetics of flesinoxan were described using a three-compartment
      model. Both the hypothermic and the corticosterone response were successfully
      described using a physiological indirect response model. It is shown that
      customizing the animal prior to the experiment has no influence on the
      pharmacokinetic-pharmacodynamic parameter estimates. Furthermore, the similarity
      in potency between the hypothermic and corticosterone effects suggests that both
      are mediated via tissues with a similar receptor-effector coupling efficiency.

PMID- 12065194
TI  - Boosting effect of morphine on alcohol drinking is suppressed not only by
      naloxone but also by the cannabinoid CB1 receptor antagonist, SR 141716.
AB  - The present study investigated the effect of the cannabinoid CB(1) receptor
      antagonist, SR 141716 (N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4
      methyl-3-pyrazole-carboxamide), on the ability of low and high doses of morphine
      to, respectively, augment and suppress voluntary alcohol intake in selectively
      bred Sardinian alcohol-preferring rats. Acute administration of a low dose of
      morphine (1 mg/kg, s.c.) produced a specific and marked increase in alcohol
      intake, which correlated with an increase in blood alcohol levels and was
      prevented by either SR 141716 (0.3 mg/kg, i.p.) or naloxone (0.1 mg/kg, i.p.). A
      higher dose (10 mg/kg, s.c.) of morphine reduced both alcohol and food intakes
      and produced sedation and hypomotility. The suppressant effect of morphine on
      alcohol intake was blocked by naloxone (0.1 mg/kg, i.p.) but not by SR 141716
      (0.3 mg/kg, i.p.). These results are in agreement with those showing the ability
      of SR 141716 to antagonize the appetitive and positive reinforcing properties of
      morphine and add further support to the hypothesis of the existence of a
      functional link between the action of opioids and of cannabinoids.

PMID- 12065195
TI  - Naloxone methiodide reverses opioid-induced respiratory depression and analgesia
      without withdrawal.
AB  - Illicit opioid overdoses are a significant problem throughout the world, with
      most deaths being attributed to opioid-induced respiratory depression which may
      involve peripheral mechanisms. The current treatment for overdoses is naloxone
      hydrochloride, which is effective but induces significant withdrawal. We propose
      that selectively peripherally acting opioid receptor antagonists, such as
      naloxone methiodide, could reverse respiratory depression without inducing
      predominantly centrally mediated withdrawal. Acute administration of morphine
      (300 mg/kg, i.p.) was found to significantly depress respiratory rate and induce
      analgesia (P<0.0001). Both naloxone hydrochloride and naloxone methiodide were
      able to reverse these effects but naloxone methiodide precipitated no significant
      withdrawal. Naloxone methiodide was also able to reverse opioid-induced
      respiratory depression (P<0.001) and antinociception (P<0.01) after chronic
      morphine administration (300 mg/kg/day for 5 days) without inducing significant
      withdrawal. Therefore, peripherally selective opioid receptor antagonists should
      be investigated as possible treatments for opioid-induced respiratory depression
      which do not induce adverse effects, such as withdrawal.

PMID- 12065196
TI  - Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine
      and fluoxetine.
AB  - Hypothalamic 5-HT (serotonin) regulates food intake, energy expenditure and
      bodyweight. Using in vivo microdialysis, we determined the effects of various
      anorectic drugs on hypothalamic extracellular 5-HT levels during the dark phase
      when rats predominantly feed. Phentermine and aminorex, which were originally
      considered to be catecholaminergic drugs, markedly increased 5-HT efflux in rat
      hypothalamus. Their actions were less profound than D-fenfluramine, but
      considerably greater than that of the selective 5-HT reuptake inhibitor,
      fluoxetine. This suggests that enhanced hypothalamic 5-HT function could be
      involved in their anorectic actions. Pharmacological characterization revealed
      that D-fenfluramine, aminorex and probably also phentermine potentiate synaptic 5
      HT function predominantly by release, whereas fluoxetine acts exclusively by
      reuptake inhibition. The results also revealed that the combined actions of
      phentermine and D-fenfluramine on hypothalamic extracellular 5-HT levels were
      additive, but not synergistic. In contrast, there was a significant negative
      cooperative effect on extraneuronal 5-HT of combining phentermine with
      fluoxetine.

PMID- 12065197
TI  - Spinal nociceptin inhibits septide but not N-methyl-D-aspartate-induced
      nociceptive behavior in rats.
AB  - Nociceptin can induce spinal analgesia in rats. Here, we tested the ability of
      nociceptin to inhibit the nociceptive behavior (biting, scratching, licking)
      induced by intrathecal administration of N-methyl-D-aspartate (4 microg) or the
      tachykinin NK(1) receptor agonist, septide (0.5 microg), in rats. Intrathecal
      nociceptin (3-30 nmol) did not modify the NMDA-induced behavior. However,
      coadministration of nociceptin (1-10 nmol) inhibited the septide-induced
      excitatory response. This inhibition was unaffected by systemic (10 mg/kg) or
      intrathecal (30 nmol) administration of naloxone, but intrathecal
      coadministration of the ORL1 (opioid receptor-like type 1) receptor antagonist
      [Nphe(1)]nociceptin-(1-13)-NH(2) (30-90 nmol) prevented it, suggesting the
      involvement of ORL1 receptors.

PMID- 12065198
TI  - Acamprosate decreases the induction of tolerance and physical dependence in
      morphine-treated mice.
AB  - The effects of acamprosate, a drug thought to interact with N-methyl-D-aspartate
      (NMDA) receptors in the central nervous system (CNS), were examined on the
      antinociceptive action of morphine, induction of tolerance to and physical
      dependence on morphine, and expression of the abstinence syndrome to the opiate
      in mice. For the induction of tolerance and dependence, morphine (300 mg/kg) was
      administered by means of a slow-release preparation. Single doses of acamprosate
      (50, 100, 200, or 400 mg/kg) administered 30 min before a test dose of morphine
      did not change the antinociceptive effects of morphine in drug-naive mice. The
      drug was also administered in repeated doses (50, 100, 200, or 400 mg/kg, 30 min
      before and 12 and 24 h after the priming dose of morphine) in order to evaluate
      its effects on the induction of tolerance; all doses assayed, except the 400
      mg/kg, did not affect the intensity of tolerance. The acute administration of
      acamprosate (50, 100, 200, or 400 mg/kg, injected 30 min before naloxone to
      morphine-pretreated mice) did not affect the intensity of the abstinence
      behavior. However, the repeated administration of 100 mg/kg of acamprosate (30
      min before and 12 and 24 h after the priming dose of morphine) decreased the
      intensity of physical dependence. The results of these studies suggest that
      acamprosate may have modulatory effects on glutamatergic neurotransmission
      participating in the adaptive mechanisms induced by chronic morphine treatment.

PMID- 12065199
TI  - The antinociceptive effect of intrathecal kynurenic acid and its interaction with
      endomorphin-1 in rats.
AB  - Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic
      glutamate receptors, with preferential affinity for the glycine-binding site of
      the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to
      investigate the antinociceptive potency of continuously administered kynurenic
      acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal
      test in awake rats. The possible interaction between kynurenic acid and the
      endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the
      same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly
      decreased the thermal hyperalgesia and increased the paw withdrawal latencies on
      the non-inflamed side. These doses were also associated with motor impairment on
      both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but
      did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min)
      on the inflamed side. There was no sign of motor impairment during the combined
      treatment. These findings demonstrate that the combination of low doses of these
      two endogenous ligands provides effective and well-controlled antinociception
      without side effects.

PMID- 12065200
TI  - Sex differences in the motor inhibitory and stimulatory role of dopamine D1
      receptors in rats.
AB  - We investigated sex differences in the motor responses to the full and selective
      dopamine D1-like receptor agonist, (+/-)-6-chloro-7,8-dihydroxyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297; 0.3, 3, and 10 mg/kg, s.c.),
      in non-habituated adult rats. In general, SKF-81297 produced a biphasic effect on
      motor activity (including locomotion, rearing and exploratory activity) which
      consisted of an initial short inhibition followed by a long-lasting stimulation.
      These effects were dose- and sex-dependent. The inhibitory phase was more
      pronounced in males than females while the opposite was true for the stimulatory
      phase. Importantly, the motor inhibitory effects of SKF-81297 were not due to an
      increase in stereotypy (e.g., grooming activity). These biphasic effects on
      several motor parameters suggest the presence of two distinct dopamine D1
      receptor populations which have opposite effects on motor activity and which are,
      in part, sexually dimorphic.

PMID- 12065201
TI  - The novel guanidine ME10092 protects the heart during ischemia-reperfusion.
AB  - The novel guanidine N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine
      [ME10092; a metabolite to the strongly cardioprotective hydroxyguanidine N-(3,4
      dimethoxy-2-chlorobenzylideneamino)-N'-hydroxyguanidine (PR5)] was administered
      intravenously to rats subjected to left coronary artery clamping followed by
      reperfusion. Administration of 1-10 mg/kg of ME10092 1 or 5 min before 10 min of
      coronary artery occlusion followed by 20 min reperfusion significantly and dose
      dependently inhibited the reperfusion-induced burst of arrhythmia, and markedly
      improved the survival of the animals. This dose schedule also dose-dependently
      and significantly inhibited the ST-segment elevation seen on the ECG during the
      artery occlusion, and attenuated the secondary rise in ST-segment during the
      reperfusion. Even when ME10092 was administered 5 min after the start of the
      reperfusion, the ST-segment elevation became significantly attenuated.
      Administration of ME10092 (3 plus 1.5 mg/kg) to animals subjected to 1 h left
      coronary occlusion followed by 2 h reperfusion reduced the heart infarction size
      by about 40%. ME10092 also dose-dependently reduced the heart rate, both during
      normal conditions and during ischemia and reperfusion. Moreover, the highest dose
      of ME10092 used (10 mg/kg) strongly attenuated the reduction in blood pressure
      seen during 10 min left coronary occlusion, as well as it attenuated the rebound
      rise in blood pressure seen during the 20 min reperfusion phase; that is,
      resulting in a normalisation of the blood pressure disturbances caused by the
      ischemia-reperfusion. We also showed that after its p.o. administration, the PR5
      hydroxyguanidine became completely metabolised to its guanidine ME10092, with no
      detectable traces of PR5 being present 30 and 60 min after the administration.
      Moreover, after the p.o. administration of ME10092, no signs of the formation of
      PR5 were seen on analysis of the rats' plasma. In view of the practically
      indistinguishable pharmacological effects of ME10092 and PR5, we suggest the
      strong cardioprotective effects of these compounds to be mediated by a direct
      effect by ME10092 per se.

PMID- 12065202
TI  - Effect of endotoxin on doxorubicin transport across blood-brain barrier and P
      glycoprotein function in mice.
AB  - The aim of this study was to investigate whether Klebsiella pneumoniae endotoxin
      modifies transport of doxorubicin, a P-glycoprotein substrate, across the blood
      brain barrier and P-glycoprotein function in mice. Doxorubicin (30 mg/kg) was
      administered into the tail vein or fluorescein isothiocyanate-labeled dextran (FD
      4) was infused (20 microg/min) into the right jugular vein of mice intravenously
      injected with endotoxin (10 mg/kg) 6 or 24 h earlier. Blood and brain samples
      were collected 4 h after injection of doxorubicin or 1 h after infusion of FD-4.
      We examined using Western blotting the influence of endotoxin on the expression
      of P-glycoprotein in brains obtained 6, 12 and 24 h after injection. Endotoxin
      did not change the plasma and brain concentrations and brain-to-plasma
      concentration ratio (K(p) value) of FD-4. No histopathological changes in brain
      capillaries were observed. These results suggest that endotoxin does not cause
      damage to brain capillaries. Plasma and brain concentrations of doxorubicin in
      mice treated 6 h earlier with endotoxin were significantly higher than those in
      control and mice treated 24 h earlier. However, endotoxin did not significantly
      change the K(p) value of doxorubicin. The protein level of P-glycoprotein was
      significantly, but slightly down-regulated 6 h after endotoxin treatment.
      However, the levels remained almost unchanged after 12 and 24 h. The present
      results suggest that Klebsiella pneumoniae endotoxin has no effect on the brain
      capillary integrity and doxorubicin transport across the blood-brain barrier in
      mice. It is likely that P-glycoprotein function might be sufficient to transport
      doxorubicin in spite of decreased levels of P-glycoprotein in the brain.

PMID- 12065203
TI  - Characterization of some novel alpha 1-adrenoceptor antagonists in human
      hyperplastic prostate.
AB  - We synthesized some quinazoline-based compounds, such as FH-71 (ethyl 4-(3-(4-(2
      methoxyphenyl)piperazinyl)aminoquinazolin-2-carboxylate), EW-65 (4-(3-(4-(2
      methoxyphenyl)piperazinyl)propyl)aminoquinazolin-2-carboxamide) and EW-154 (2-(4
      (4-(2-methoxyphenyl)piperazinyl)butyl)amino-4-cyclohexylamino-quinazolin), and
      then characterized their pharmacological properties in several tissues. All of
      these compounds produced potent inhibition of phenylephrine but not high K(+) or
      U46619 (11 alpha,9 alpha-epoxymethano-15S-hydroxy-prosta-5Z,13E-dienoic acid)
      induced contractions in rat aorta, suggesting alpha(1)-adrenoceptor antagonist
      properties. With rat vasa deferentia and spleens as the functional alpha(1A)- and
      alpha(1B)-adrenoceptor models, respectively, FH-71 exhibited greater antagonistic
      potency in rat vas deferens, EW-154 in rat spleen, and EW-65 had similar effects
      in both tissues. The potency ratios of terazosin, FH-71, EW-65 and EW-154 against
      phenylephrine-induced contractions in rat vas deferens/spleen were 1, 19.04, 0.39
      and 0.09, respectively. The results suggest that FH-71 is a selective alpha(1A)
      adrenoceptor antagonist, whereas EW-154 exhibits more antagonistic selectivity
      against alpha(1B)-adrenoceptors. FH-71 also showed a greater potency than EW-65
      and EW-154 against phenylephrine-induced contraction in human hyperplastic
      prostate. The pA(2) values were 8.34, 7.44 and 7.05, respectively. Furthermore,
      FH-71 and EW-65 were not cytotoxic whereas EW-154 (all in 10 microM) had a
      massive toxic effect (more than 80%) in human prostatic smooth muscle cells.
      These data show FH-71 to be a potent and selective alpha(1A)-adrenoceptor
      antagonist with activity in human hyperplastic prostate.

PMID- 12065204
TI  - Timing of pentoxifylline treatment determines its protective effect on diabetes
      development in the Bio Breeding rat.
AB  - Diabetes-prone Bio Breeding (DP-BB) rats spontaneously develop diabetes between
      60 and 120 days of age. Diabetes-resistant (DR)-BB rats can be induced to develop
      diabetes by poly(I:C) and anti-RT6. Here, we studied the effect of
      pentoxifylline, a potent anti-inflammatory agent, on diabetes development in both
      BB rat models of insulin-dependent diabetes mellitus and investigated whether
      these effects were related to differential modulation of tumour necrosis factor
      (TNF)-alpha and interleukin-10. When DP-BB rats received pentoxifylline from day
      60 onwards, diabetes development was delayed and reduced. The other treatment
      protocols had no effect. In DR-BB rats, pentoxifylline treatment resulted only in
      a delay of diabetes development. In both BB rat models, in vivo pentoxifylline
      treatment potently suppressed TNF-alpha, but only moderately affected interleukin
      10 production in vitro. These results show that timing of pentoxifylline
      treatment determines its protective effect on diabetes development in DP-BB rats.
      The observed pentoxifylline-induced increase of the interleukin-10/TNF-alpha
      ratio might be a mechanism for protection or delay of the diabetes development.

PMID- 12065205
TI  - Early acarbose treatment ameliorates resistance of insulin-regulated GLUT4
      trafficking in obese Zucker rats.
AB  - Genetically (fa/fa) obese Zucker rats represent an established model of impaired
      glucose tolerance, with profound insulin resistance. Acarbose, an inhibitor of
      alpha-glucosidases, attenuates postprandial blood glucose peaks, and improves
      glucose tolerance in these animals. In the present study, we have tested the
      hypothesis that the effect of acarbose is associated with improved glucose
      transporter isoform 4 (GLUT4) trafficking in muscle tissue. Acarbose was
      administered to Zucker rats as a dietary admix (40 mg/100 g diet) for 12 weeks
      starting at the age of 6 weeks. Serum insulin and leptin were reduced by acarbose
      from 44 to 19 and 144 to 62 ng/ml, respectively. Glucose tolerance test was
      performed by i.v. injection of glucose (1 g/kg) and determination of serum
      glucose up to 60 min. Marked impaired glucose tolerance was observed in obese
      animals with a profound correction of this defect in acarbose-treated rats.
      Insulin-regulated translocation of GLUT4 to the plasma membrane in soleus muscle
      was increased twofold in lean animals, with a totally blunted response in obese
      rats. Acarbose feeding restored a 1.6-fold effect of insulin on GLUT4
      translocation. The exocytotic GLUT4 storage pool in cardiac muscle was completely
      insulin-insensitive in obese animals, with a largely improved response after
      acarbose feeding. Activation of Akt, an insulin signaling event upstream of
      GLUT4, was completely normalized in acarbose-treated rats. In conclusion, we show
      here that early application of acarbose to obese Zucker rats can prevent the
      development of impaired glucose tolerance and obesity-associated insulin
      resistance at the level of the muscle cell, as reflected by an amelioration of
      defective GLUT4 trafficking in both cardiac and skeletal muscles.

PMID- 12065206
TI  - DNA hypomethylating agents 5-aza-2'-deoxycytidine and valproate increase neuronal
      5-lipoxygenase mRNA.
AB  - DNA methylation regulates gene expression. Neuronal 5-lipoxygenase expression
      increases during aging and during the proliferation of immature rat cerebellar
      granule neurons. In these cultures, we investigated the effects of
      hypomethylating agents 5-aza-2'-deoxycytidine (AdC) and valproate on 5
      lipoxygenase mRNA. Both drugs increased 5-lipoxygenase mRNA in proliferating
      cells; only valproate was effective in differentiated neurons. We propose that
      neuronal 5-lipoxygenase expression can be affected by aging-altered DNA
      methylation and by hypomethylating drugs, such as the anticonvulsant valproate.

PMID- 12065207
TI  - Variants of the CYP11B2 gene predict response to therapy with candesartan.
AB  - In a prospective trial, patients with an elevated diastolic blood pressure (above
      95 mm Hg) received high-dose (16 mg) or low-dose (8 mg) candesartan in addition
      to standardised medication. A positive response to treatment was defined as a
      diastolic blood pressure <85 mm Hg at follow-up. Genotyping for two candidate
      genes was performed in 116 patients. Genotypes of the CYP11B2 promotor
      polymorphism significantly predicted a positive response to treatment (CC: 67%;
      TC: 34%; TT: 21%; p=0.005).

PMID- 12065208
TI  - Safety assessment of allylalkoxybenzene derivatives used as flavouring substances
      - methyl eugenol and estragole.
AB  - This publication is the seventh in a series of safety evaluations performed by
      the Expert Panel of the Flavor and Extract Manufacturers' Association (FEMA). In
      1993, the Panel initiated a comprehensive program to re-evaluate the safety of
      more than 1700 GRAS flavouring substances under conditions of intended use. In
      this review, scientific data relevant to the safety evaluation of the
      allylalkoxybenzene derivatives methyl eugenol and estragole is critically
      evaluated by the FEMA Expert Panel. The hazard determination uses a mechanism
      based approach in which production of the hepatotoxic sulfate conjugate of the 1'
      hydroxy metabolite is used to interpret the pathological changes observed in
      different species of laboratory rodents in chronic and subchronic studies. In the
      risk evaluation, the effect of dose and metabolic activation on the production of
      the 1'-hydroxy metabolite in humans and laboratory animals is compared to assess
      the risk to humans from use of methyl eugenol and estragole as naturally
      occurring components of a traditional diet and as added flavouring substances.
      Both the qualitative and quantitative aspects of the molecular disposition of
      methyl eugenol and estragole and their associated toxicological sequelae have
      been relatively well defined from mammalian studies. Several studies have clearly
      established that the profiles of metabolism, metabolic activation, and covalent
      binding are dose dependent and that the relative importance diminishes markedly
      at low levels of exposure (i.e. these events are not linear with respect to
      dose). In particular, rodent studies show that these events are minimal probably
      in the dose range of 1-10 mg/kg body weight, which is approximately 100-1000
      times the anticipated human exposure to these substances. For these reasons it is
      concluded that present exposure to methyl eugenol and estragole resulting from
      consumption of food, mainly spices and added as such, does not pose a significant
      cancer risk. Nevertheless, further studies are needed to define both the nature
      and implications of the dose-response curve in rats at low levels of exposure to
      methyl eugenol and estragole.

PMID- 12065209
TI  - Trehalose: a review of properties, history of use and human tolerance, and
      results of multiple safety studies.
AB  - This paper contains a review of the history, natural occurrence, human
      consumption, metabolism, manufacture, and the results of eight standardized
      animal safety studies using trehalose. Trehalose (alpha,alpha-trehalose) is a
      naturally occurring sugar containing two D-glucose units in an alpha,alpha-1,1
      linkage. Trehalose functions in many organisms as an energy source or a
      protectant against the effects of freezing or dehydration. It also possesses
      physical and/or chemical properties that are different than other sugars, which
      may make trehalose an attractive ingredient in food, health and beauty and
      pharmaceutical products. Data are presented supporting safe human consumption of
      trehalose in doses up to 50 g, and the physiologic ability of humans to digest
      it. No consistent treatment-related, dose-dependent adverse effects were observed
      in any of the eight safety studies performed at doses up to 10% of the diets. On
      the basis of these toxicity studies, human studies in which doses of trehalose
      were administered to various populations, and consumption of trehalose in
      commercial products in Japan, it is concluded that trehalose is safe for use as
      an ingredient in consumer products when used in accordance with current Good
      Manufacturing Practices.

PMID- 12065210
TI  - Antifreeze proteins: characteristics, occurrence and human exposure.
AB  - Antifreeze proteins (AFPs), also known as ice structuring proteins, bind to and
      influence the growth of ice crystals. Proteins with these characteristics have
      been identified in fish living in areas susceptible to ice formation and in
      numerous plants and insects. This review considers the occurrence of AFPs and
      relates it to the likely intake by human populations, with a view to forming a
      judgment about their safety in foods. Intake of AFPs in the diet is likely to be
      substantial in most northerly and temperate regions. Much of this intake is
      likely to be from edible plants, given their importance in the diet, but in some
      regions intake from fish will be significant. Inadequate data exist to estimate
      intakes from plants but estimates of intake of AFP from fish are presented for
      two countries with very different fish consumption, the USA and Iceland. Typical
      short-term exposure, for instance a portion of cod may contain up to 196 mg AFGP,
      while the AFP content of the same weight of ocean pout would be up to 420 mg.
      Average available fish AFP in the diet is calculated to be around 1-10 mg/day in
      the USA and 50-500 mg/day in Iceland, but these estimates are subject to
      considerable uncertainty. As far as can be ascertained, AFPs are consumed with no
      evidence of adverse health effects, either short- or long-term. Given the
      structural diversity of AFPs, one firm general conclusion that can be drawn from
      the history of consumption of AFPs is that their functional characteristics do
      not impart any toxicologically significant effect, in a way that, for instance, a
      property such as cholinesterase inhibition would. Furthermore, specifically in
      the case of fish AFPs where some consumption data are available, it is reasonable
      to infer a lack of allergenicity from the absence of reports of this effect.

PMID- 12065211
TI  - Low-dose in utero effects of xenoestrogens in mice and their relevance to humans:
      an analytical review of the literature.
AB  - Several lines of evidence suggest that mouse embryos are sensitive to naturally
      occurring and environmental estrogens. These include prostatic enlargement post
      partum in male fetuses exposed in utero to low doses of estradiol,
      diethylstilbestrol (DES) or bisphenol A (BPA). The NIEHS/EPA Endocrine Disruptors
      Low Dose Peer Review Panel evaluated the relevant studies and concluded that
      while credible evidence exists for low dose effects of BPA, the effect had not
      been established as a "general and reproducible finding" based on the number and
      power of negative studies. The Panel suggested that the discrepancies in data
      were attributed to conditions, such as intrauterine position, environmental
      factors, and genetic factors. An issue that is potentially relevant to the health
      implications of low-dose xenoestrogen exposure in utero, and not previously
      addressed, is the comparative physiology of gestation in the mouse and human.
      These two species differ with regard to the extent of involvement and hormonal
      control of the corpus luteum, organs involved in progestin and estrogen
      secretion, the specific estrogens produced, and estrogen blood levels attained in
      the mother and embryo. On the basis of these species differences (particularly,
      the markedly higher estrogen levels attained in human pregnancy compared to the
      mouse), it would appear unlikely that low doses of BPA or other xenoestrogens
      produce adverse endocrine disruptive effects during human pregnancy.

PMID- 12065212
TI  - Inhibition of thyroid type 1 deiodinase activity by flavonoids.
AB  - Some dietary flavonoids inhibit thyroperoxidase and hepatic deiodinase activity,
      indicating that these compounds could be classified as anti-thyroid agents. In
      this study, we evaluated the in vitro effect of various flavonoids on thyroid
      type 1 iodothyronine deiodinase activity (D1). D1 activity was measured in murine
      thyroid microsome fractions by the release of 125I from 125I-reverse T3. D1
      activity was significantly inhibited by all the flavonoids tested; however, the
      inhibitory potencies on thyroid D1 activity differed greatly among them. A 50%
      inhibition of D1 activity (IC(50)) was obtained at 11 microM baicalein, 13 microM
      quercetin, 17 microM catechin, 55 microM morin, 68 microM rutin, 70 microM
      fisetin, 72 microM kaempferol and 77 microM biochanin A. Our data reinforce the
      concept that dietary flavonoids might behave as antithyroid agents, and possibly
      their chronic consumption could alter thyroid function.

PMID- 12065213
TI  - Effect of an extract of cauliflower (leaf) on the labeling of blood elements with
      technetium-99m and on the survival of Escherichia coli AB1157 submitted to the
      treatment with stannous chloride.
AB  - The labeling of red blood cells (RBC) with technetium-99m (99mTc) depends on a
      reducing agent and stannous chloride (SnCl(2)) and is widely utilized. This
      labeling may also be altered by drugs, and SnCl(2) reduces the survival of
      Escherichia coli cultures. Cauliflower (Brassica oleracea L. var. botrytis) is
      used in folk medicine and we evaluated its influence on (i) the labeling of blood
      elements with 99mTc, and (ii) on the survival of an E. coli strain. Blood was
      withdrawn from rats that drank the extract of cauliflower (15 days). Blood was
      incubated with SnCl(2) and with 99mTc, as sodium pertechnetate, centrifuged and
      plasma (P) and RBC were isolated. Samples of P and RBC were also precipitated,
      centrifuged and soluble and insoluble fractions isolated. E. coli culture was
      treated with SnCl(2) in the presence of cauliflower. The extract of cauliflower
      did not alter the fixation of 99mTc on blood fractions; however, it abolished the
      lethal effect of SnCl(2) on the E. coli culture. We suggest that the substances
      present in the extract of cauliflower probably, would have redox property with
      different mechanisms of action. The oxidant action of the substances of the
      extract would not be strong enough to oxidise the stannous ions altering the
      99mTc-labeling. However, the referred substances could oxidise these ions
      sufficiently to protect the E. coli culture against the lethal effect of the
      stannous ion.

PMID- 12065214
TI  - Inhibition of aromatase activity by green tea extract catechins and their
      endocrinological effects of oral administration in rats.
AB  - We orally administered polyphenone-60 (P-60), green tea extract catechins, in the
      diet (0, 1.25 and 5%) to male rats for 2, 4 and 8 weeks initiated at 5 weeks old.
      It was found that a 5% dose to male rats for 2-8 weeks induced goiters and
      decreased weights of the body, testis and prostate gland. Endocrinologically,
      elevating plasma thyroid stimulating hormone (TSH), luteinizing hormone (LH) and
      testosterone levels and decreasing tri-iodothyronine (T(3)) and thyroxine (T(4))
      levels were induced by this treatment. We also found that P-60 as a whole and
      some of its constituents exhibited inhibitory effects on human placental
      aromatase activity by in vitro assay. The concentration of P-60 that required
      producing 50% inhibition of the aromatase activity (IC(50) value) was 28
      microg/ml. The IC(50) values of (-)-catechin gallate (Cg), (-)-epigallocatechin
      (EGC), (-)-epigallocatechin gallate (EGCg) and (-)-gallocatechin gallate (GCg)
      were 5.5 x 10(-6), 1.0 x 10(-4), 6.0 x 10(-5) and 1.5 x 10(-5) M, respectively. (
      )- Epicatechin gallate (ECg) at 1.0 x 10(-4) M produced 20% inhibition. (-)
      Epicatechin (EC) and (+)-catechin (CT) exhibited no effects on aromatase
      activity. The endocrinological changes observed in vivo were in conformity with
      antithyroid effects and aromatase inhibition effects of P-60 and its
      constituents.

PMID- 12065216
TI  - Evaluation of the genotoxic effect of rutin and quercetin by comet assay and
      micronucleus test.
AB  - Flavonoids are phenolic compounds, naturally found in vegetables, tea and red
      wines. A recent study has demonstrated that the flavonoids rutin and quercetin
      show a protective role against the deleterious effects of free radicals in
      cirrhotic rats. Considering this finding and the controversial results concerning
      the mutagenicity of rutin and quercetin recorded in the literature, the capacity
      of these flavonoids to cause damage to the DNA was evaluated using the alkaline
      single-cell gel electrophoresis (SCG) and micronucleus test in the bone marrow of
      mice. The doses for both compounds were 2 x 2500, 2 x 1250 and 2 x 625 mg/kg.
      Micronucleus test showed that rutin caused no damage to the DNA of the mice bone
      marrow cells, and the SCG assay demonstrated an increase of damage only at the
      dose of 2 x 1250 mg/kg. But when the mice cells of the three quercetin doses were
      compared with the negative control, significantly higher damage was observed by
      SCG assay, although not proportional to the dose. The micronucleus test also
      demonstrated a significant increase of damage, but only at the 2 x 1250 mg/kg
      dose. Considering the results obtained in this study with very high doses, it is
      unlikely that the consumption of rutin and quercetin produces any clastogenic
      effects. Our results also indicated that SCG could profitably be used in drug
      genotoxicity evaluation protocols.

PMID- 12065215
TI  - In vitro effect of eugenol and cinnamaldehyde on membrane potential and
      respiratory chain complexes in isolated rat liver mitochondria.
AB  - The effect of water extracts of cinnamon and clove on rat mitochondrial
      F(0)F1ATPase was investigated. Both spices stimulated ATP hydrolysis. Gas
      chromatography analysis of the water extracts, confirmed the presence of eugenol
      and cinnamaldehyde as major components in clove and cinnamon, respectively. Both
      components (1) stimulated ATPase significantly at concentrations equal or greater
      then 0.3 mM; (2) reduced mitochondrial membrane potential: a 50% decrease in
      Deltapsi was obtained at 7.56 and 11.6 micromoles/mg protein for eugenol and
      cinnmaldehyde, respectively; (3) inhibited NADH oxidase or complex I of the
      respiratory chain with a 50% inhibition at 15 and 20 micromoles/mg protein for
      eugenol and cinnamaldehyde respectively; (4) had no effect on succinate
      dehydrogenase activity. The study proposes the mitochondria as a target for the
      action of the spices resulting in derangement of mitochondrial functions,
      particularly at proton transferring sites.

PMID- 12065217
TI  - Volatile N-nitrosamine inhibition after intake Korean green tea and Maesil
      (Prunus mume SIEB. et ZACC.) extracts with an amine-rich diet in subjects
      ingesting nitrate.
AB  - The formation of carcinogenic nitrosamines under simulated gastric conditions was
      studied during the incubation of amine rich food and nitrate, and its possible
      inhibition by adding kumquat, sweet orange, strawberry, garlic, kale juices,
      Maesil (Prunus mume) and green tea extracts. The strawberry, kale juices, Maesil
      and green tea extracts were equally effective in reducing the formation of N
      nitrosodimethylamine (NDMA). The fruits of P. mume SIEB. et ZACC. (Korean name,
      Maesil) have been used as a traditional drug and health food in Korea. During
      four weeks of test (designated EW1, EW2, EW3 and EW4; experiment week 1, 2, 3 and
      4 diets) volunteers consumed a diet of low nitrate and amine (EW1) and consumed a
      fish meal rich in amines as nitrosatable precursors in combination with intake of
      nitrate-containing drinking water without (EW2) or with Maesil and green tea
      extracts (EW3 and EW4, respectively). The intake of nitrate-containing drinking
      water (340 mg nitrate/100 ml) resulted in a significant rise in mean salivary
      nitrate and nitrite concentrations and in mean urinary nitrate levels. Mean
      urinary nitrate was increased to 455.0+/-66.2, 334.6+/-67.8 and 333.4+/-50.7
      mg/18 h after the nitrate intake of EW2, EW3 and EW4, respectively. Significant
      increases in urinary dimethylamine and trimethylamine levels were observed in
      consumption of diets (EW2, EW3, and EW4) rich in amine and nitrate. Maesil and
      green tea extract in EW3 and EW4 enhanced the increase of urinary dimethylamine
      and trimethylamine levels. Urinary excretion of N-nitrosodimethylamine in
      consumption of diet rich in nitrate and amine (EW2) increased to 6504.4+/-2638.7
      ng/18 h from 257.0+/-112.0 ng/18 h of low nitrate and amine diet (EW1). Korean
      green tea and Maesil extracts in nitrate and amine rich diet reduced the
      excretion of N-nitrosodimethylamine to 249.7+/-90.6 and 752.7+/-595.3 ng/18 h,
      respectively, compared with 6504.4+/-2638.7 ng /18 h after ingestion of TD1 diet.

PMID- 12065218
TI  - Evaluation of the developmental toxicity of crocetin on Xenopus.
AB  - Crocetin, a carotenoid isolated from the spice saffron, has been found to be
      effective in treating certain types of cancer treatable with all-trans retinoic
      acid (ATRA). ATRA, however, is a potent teratogen, and the possibility that
      crocetin may also be a teratogen becomes an important medical issue. The
      teratogenic potential of crocetin and ATRA were evaluated in frog (Xenopus)
      embryos. The data show that crocetin is a teratogen, but far less potent than
      ATRA. This suggests that crocetin may be a safer alternative to treat ATRA
      sensitive cancers in women of childbearing age.

PMID- 12065219
TI  - Sequence analysis and resistance to pepsin hydrolysis as part of an assessment of
      the potential allergenicity of ice structuring protein type III HPLC 12.
AB  - The recently published WHO/FAO guidelines on the assessment of allergenicity of
      novel food proteins provide a strategy with which to approach the determination
      of the potential of novel proteins in foods to be allergens. Key to this strategy
      are the assessment of sequence similarity to known allergens and the assessment
      of the resistance to pepsin hydrolysis. Ice structuring proteins (also commonly
      referred to as anti-freeze or thermal hysteresis proteins) are a group of
      naturally occurring proteins that bind to ice and structure ice crystal
      formation. The amino acid sequence of the ice structuring protein (ISP) type III
      HPLC 12 (ISP type III) was compared in silico with the sequences of known
      allergens. Secondly, the resistance to pepsin hydrolysis of ISP type III and its
      glycoconjugates (produced in recombinant baker's yeast) was assessed. The results
      indicate that ISP type III has no sequence similarity with known allergenic
      proteins. Both ISP type III and ISP type III glycoconjugates contained within the
      fermentation product were hydrolysed readily by pepsin (50% loss in <10 min at pH
      1.5) to give peptide fragments that were too small to be allergenic or to trigger
      cross-linking to IgE. In an accompanying study, we demonstrated that IgE from
      fish-allergic individuals did not bind ISP Type III. Therefore, in accordance
      with the WHO/FAO strategy, the assessment of ISP type III and ISP type III
      glycoconjugates by sequence analysis together with lack of resistance to pepsin
      hydrolysis and the absence of IgE binding supports the conclusion that both are
      unlikely to present a potential sensitisation hazard.

PMID- 12065220
TI  - DNA damage and the effect of antioxidants in streptozotocin-treated mice.
AB  - Streptozotocin (STZ) has drawn attention as a potential source of oxidative
      stress, which induces genotoxicity. We investigated the effects of STZ on DNA
      damage in the liver and kidney, as well as the protective effects of
      antioxidants, by using the alkaline single-cell gel electrophoresis assay, and by
      measuring the ratio of 8-hydroxy-2'-deoxyguanosine (8-OHdG) to dG. A single
      intraperitoneal injection of STZ (150 mg/kg) increased serum levels of glucose,
      aspartate aminotransferase (AST), alanine aminotransferase (ALT) and blood urea
      nitrogen (BUN), and also caused DNA damage in the liver and kidney, which
      recovered slowly with time. Antioxidants,(ascorbic acid, trolox and probucol)
      prevented the STZ-induced elevation of DNA damage in the liver and kidney and
      inhibited the increase in serum levels of AST, ALT and BUN. Thus ascorbic acid,
      trolox, and probucol protected the mice against STZ-induced DNA damage that might
      contribute to the development of hepatic or renal disease.

PMID- 12065221
TI  - Effects of soy sauce and sugar on the formation of heterocyclic amines in
      marinated foods.
AB  - The effects of soy sauce and sugar on the formation of heterocyclic amines (HAs)
      in marinated pork, eggs, and bean cakes were studied. Food samples were immersed
      in water in the presence of various levels of soy sauce and sugar, and the
      mixtures were subjected to simmering at 98+/-2 degrees C for 1 h in a closed
      saucepan. The various HAs in marinated food samples were analyzed by HPLC with
      photodiode-array detection. Results showed that seven HAs: 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ); 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
      (MeIQx); 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ); 2-amino-3,4,8
      trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx); 3-amino-1,4-dimethyl-5H
      pyrido[4,3-b]indole (Trp-P-1); 2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine
      (PhIP); and 2-amino-9H-pyrido[2,3,-b]indole (AalphaC) were detected in marinated
      pork, while five HAs: IQ, MeIQx; 4,8-DiMeIQx; PhIP; and AalphaC in bean cakes, as
      well as four HAs, MeIQx, 4,8-DiMeIQx, Trp-P-1 and PhIP in eggs. In most samples
      PhIP was formed in largest amount, followed by MeIQx, 4,8-DiMeIQx, IQ, AalphaC,
      Trp-P-1 and MeIQ. The amounts of HAs produced in marinated food samples followed
      an increased order for each increasing level of soy sauce or sugar. Marinated
      juice was found to contain a higher content of HAs than marinated foods.

PMID- 12065222
TI  - Occupational and dietary exposures of humans to cyanide poisoning from large
      scale cassava processing and ingestion of cassava foods.
AB  - The biochemical and toxicological effects of occupational and dietary exposure of
      humans to cyanide poisoning from large-scale cassava processing and ingestion of
      cassava foods were investigated using spectrophotometric and enzymatic methods.
      Analysis of urinary and serum thiocyanate (cyanide metabolite) from workers in
      cassava processing industries, who were 'frequent' [those who eat cassava food(s)
      at least once a day] and 'infrequent' [those who eat cassava food(s) only
      occasionally] consumers of cassava-based diets, was carried out with the aid of
      questionnaries. The mean urinary thiocyanate level of the cassava processors
      (mean+/-S.D.; 153.50+/-25.21 micromo1/l) was 2.2 and 2.6 times higher than that
      of frequent (70.1+/-21.8 micromo1/l) and infrequent (mean+/-S.D.; 59.30+/-17.0
      micromo1/l) cassava consumers, respectively. The mean serum thiocyanate levels
      rose to 126.73+/-12.4 micromo1/l for the former and 68.4+/-18.3 and 54.7+/-13.2
      micromo1/l, respectively, for the latter. An increase in plasma activity by 10%
      above normal of aspartate aminotransferase (AST) was observed in 40% of the
      cassava processors, whereas it was within normal range in all consumers. The
      activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALK.PHOS)
      were within the normal value in all cases studied. The blood glucose level of 50%
      of the cassava processors was 100 mg/ml or above while that of the consumers was
      in the range of 68-85 mg/100 ml. The total protein, serum albumin and creatinine
      levels were in the range for normal values for the processors and consumers. The
      health implications of these findings are discussed.

PMID- 12065223
TI  - Chemical and biochemical properties of casein-sugar Maillard reaction products.
AB  - The Maillard reaction (MR) involves the condensation reaction between amino acids
      or proteins with reducing sugars, which occurs commonly in food processing and
      storage. The Maillard reaction of Glc-, Fru- and Rib-casein was generated at 55
      degrees C, pH 7.0 for up to 28 days. The browning and fluorescence of Glc- and
      Fru-casein increased with increasing heating time. The temporal development of
      browning and fluorescence of Rib-casein was relatively faster than Glc- and Fru
      casein, respectively. Glc-, Fru- and Rib-casein all exhibited antioxidant
      activity against Fenton reactant-induced hydroxyl free radicals, while only Rib
      casein exhibited a weak DPPH free radical scavenging in addition to preventing
      Fenton reactant-induced oxidation. It was suggested that casein-sugar MRPs work
      more efficiently to quench hydrophilic than hydrophobic radicals. All three MRPs
      showed no toxicity to Caco-2 cell at both low and high concentrations. There was
      no correlation between the browning and/or fluorescence temporal patterns and
      biochemical activity of the different sugar-casein generated MRPs.

PMID- 12065224
TI  - A chronic toxicity study of josamycin in F344 rats.
AB  - The chronic toxicity of josamycin was examined in Fischer 344 (F344) rats. Groups
      of 10 males and 10 females were given the test compound in the diet at
      concentrations of 0 (control), 0.02, 0.1, 0.5 or 2.5% for 52 weeks. Daily intake
      of josamycin was 0, 10, 50, 260 and 1310 mg/kg body weight in males and 0, 10,
      60, 290 and 1460 mg/kg body weight in females, respectively. Body weight gain was
      significantly (P<0.05) reduced in the male 2.5% group but no noticeable changes
      were found in food intake. In hematological examination, the platelet count was
      significantly (P<0.01) lower in the male groups given 0.02% or more of josamycin
      and in the 2.5% female group as compared with the control group values in a dose
      dependent manner. In serum biochemical examination, blood urea nitrogen was
      significantly (P<0.05 and P<0.01, respectively) higher in males given 0.5 and
      2.5% and total bilirubin was significantly (P<0.05) higher in females receiving
      2.5% as compared with those of the control group. No death occurred at any dose
      levels during the dosing period. At necropsy, with the exception of cecal
      enlargement in the groups given more than 0.1% josamysin and a significant
      (P<0.01) increase in the relative liver weight of females in the 2.5% group, no
      particular findings related to the administration were observed.
      Histopathologically, the incidence and severity of liver bile duct proliferation
      in female 2.5% group were significantly (P<0.01) greater than those of the
      control group. Other histological changes found in the treated and control groups
      were similar to the spontaneous lesions in this strain of rats in terms of the
      incidence and severity. Interestingly, the josamycin treatment reduced the
      development of altered liver cell foci in females in a dose-dependent manner.
      Thus, it is concluded that, under the present experimental conditions, josamycin
      induces bile duct proliferation in female F344 rats at a high dose of 1460 mg/kg
      body weight. Based on the decrease of platelet count found in males given 10
      mg/kg body weight or more, the no-observed-adverse-effect level (NOAEL) was
      estimated to be less than 10 mg/kg body weight.

PMID- 12065226
TI  - Toxicity and pharmacokinetics of 2-(2-dimethylaminoethoxy)ethanol following
      cutaneous dosing.
AB  - A 9-day repeated cutaneous toxicity study in the New Zealand White rabbit was
      conducted using 6-h occluded contact with 0 (water control), 50, 250 and 500 mg
      dimethylaminoethoxyethanol (DMEE)/kg. There were no clinical signs, and no
      effects on body weight, food consumption or serum chemistry. Hematological
      effects were limted to increased leukocyte count due to heterophil leukocytosis,
      increased platelet count, and decreased hemoglobin and hematocrit at the high
      dose. These findings are typical of the response of cutaneous inflammation.
      Histopathological findings were limited to the DMEE-treated skin, and consisted
      of acanthosis and ulcerative/necrotizing dermatitis. Thus, there was no evidence
      for cumulative percutaneous systemic toxicity for DMEE. The pharmacokinetics of
      DMEE was investigated in the Fischer 344 rats. Rats were given an intravenous
      dose of 15 or 150 mg/kg, or an occluded cutaneous dose of 150 mg/kg [14C]DMEE,
      and its fate was followed for 48-72 h. DMEE was readily absorbed through the skin
      (bioavailability=72-80%). Concentration in plasma rose steadily to a maximum at
      about 3.5 h after dosing, and then declined in a biphasic manner. 14C-DMEE
      derived radioactivity was distributed throughout the body, with no apparent
      sequestration in any particular organ. The highest concentrations were observed
      in the kidney, liver and lung, and the lowest concentrations were found in the
      brain and fat. Urine was the major route of excretion, with minor amounts
      eliminated in the feces and as expired CO(2). The rate of excretion was moderate,
      with about 30% of the applied dose eliminated in the first 12 h, and by 72 h
      after dosing, less than 4% of the dose remained in the carcass. Unchanged DMEE
      was the principal component detected in the urine. This observation, together
      with the less than 1% of the dose excreted as CO(2), showed that metabolism was
      not an important process in the elimination of DMEE in the rat.

PMID- 12065225
TI  - Comparison of acute toxicities of indolo[3,2-b]carbazole (ICZ) and 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) in TCDD-sensitive rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic
      hydrocarbons are environmental toxicants that act via the AH receptor (AHR). In
      vitro studies have demonstrated that some indole derivatives present in
      cruciferous vegetables also bind to the AHR. One of the highest AHR binding
      affinities is exhibited by indolo[3,2-b]carbazole (ICZ). Since exposure to these
      dietary indoles is quantitatively far larger than that to halogenated aromatic
      compounds, their potential toxic risks have raised concern. In the present study,
      we compared the effects of ICZ with those of a single dose of 20 microg/kg TCDD
      in the most TCDD-sensitive rat strain (Long-Evans [Turku AB]) (L-E). Whereas TCDD
      elicited the expected toxicity syndrome, ICZ, either as a single subcutaneous
      dose (63.5, 127 or 508 microg/kg) or with repeated sc dosing (508 microg/kg for 5
      days) failed to reproduce any toxic impacts of TCDD. Furthermore, a simultaneous
      ICZ treatment (63.5 or 127 microg/kg for 10 days) did not interfere with TCDD (20
      microg/kg; single exposure) action. A moderate hepatic induction of CYP1A1 could
      be triggered by repeated intragastric administration of ICZ (127 microg/kg for 4
      days, the last treatment 2.5 h prior to termination). In control experiments in a
      reconstituted yeast system, ICZ potently and dose-dependently activated L-E rat
      AHR function demonstrating that it represents a bona fide high-affinity ligand
      for the rat receptor in vivo. Thus, the present study does not support the view
      that dietary exposure to ICZ would present a hazard of AHR-mediated adverse
      health effects to humans.

PMID- 12065227
TI  - Impact of high bromide intake in the rat dam on iodine transfer to the sucklings.
AB  - A significant impact of high bromide levels in the organism of the mother on
      iodine transfer to the sucklings was established in experiments with female
      Wistar rats. The observed decrease in iodine transfer to the young through
      mothers' milk and/or an increase in the bromide concentration in the milk, caused
      a decrease in body weight of the pups. Enhanced bromide levels also adversely
      affected the thyroid gland of the young. High bromide intake in the lactating
      dams caused a decrease in iodide accumulation in the mammary glands, and also an
      increase in iodide elimination through the kidneys.

PMID- 12065228
TI  - Bone marrow and bone: a functional unit.
AB  - Bone and bone marrow, although often regarded as separate systems, function as a
      single unit. Cells in the bone marrow are the precursors of bone remodelling
      cells and exert an important regulatory role both on their own development and
      the remodelling process, acting as mediators for the effects of systemic and
      local factors. Other cells, such as immune cells and megakaryocytes, also
      contribute to the regulation of bone cell development and activity. Many diseases
      that affect the bone marrow have profound effects on bone, involving interactions
      between abnormal and normal marrow cells and those of bone. Although recent
      advances in bone physiology have produced new insights into the relationship
      between bone marrow and bone cells, much remains to be learnt about the
      mechanisms by which marrow and bone act in synergy to regulate bone remodelling,
      both in health and disease.

PMID- 12065229
TI  - Differential effects of interleukin-6 receptor activation on intracellular
      signaling and bone resorption by isolated rat osteoclasts.
AB  - The effects of the related cytokines interleukin-6 (IL-6), leukemia inhibitory
      factor (LIF) and oncostatin-M on bone resorption and cytosolic Ca(2+) signaling
      were compared in isolated rat osteoclasts. In the traditional disaggregated
      osteoclast (pit) assay, IL-6 and LIF, but not oncostatin-M, conserved the bone
      resorption otherwise inhibited by high extracellular [Ca(2+)] (15 mM). It
      produced a paradoxical, concentration-dependent stimulation of resorption by
      elevated extracellular Ca(2+). In the micro-isolated single osteoclast resorption
      assay, IL-6, high [Ca(2+)] or IL-6 plus high [Ca(2+)] all increased pit
      formation. In contrast, the IL-6 receptor (IL-6R)-specific agonist antibody MT-18
      inhibited bone resorption in a concentration-dependent manner (1:500 to 1:500
      000). MT-18 triggered cytosolic Ca(2+) signals in fura 2-loaded osteoclasts
      within approximately 10 min of application. Each cytosolic Ca(2+) transient began
      with a peak deflection that persisted in Ca(2+)-free, EGTA-containing
      extracellular medium, consistent with a release of intracellularly stored Ca(2+).
      This was followed by a sustained elevation of cytosolic [Ca(2+)] that was
      abolished in Ca(2+)-free medium, as expected from an entry of extracellular
      Ca(2+), and by the Ca(2+) channel antagonist Ni(2+). The inclusion of either IL-6
      or soluble human (sh) IL-6R specifically reversed both the above effects of MT
      18, confirming that both effects were specific for the IL-6R. The findings
      suggest that IL-6R activation by IL-6 stimulates osteoclastic bone resorption
      either by reversing the inhibitory effect of high extracellular Ca(2+) in stromal
      containing systems or itself stimulating bone resorption along with Ca(2+) by
      micro-isolated osteoclasts. In contrast, activation of the IL-6R by an agonist
      antibody produces an inhibition of bone resorption and an associated triggering
      of the cytosolic Ca(2+) signals previously associated with regulation of bone
      resorptive function in other situations.

PMID- 12065230
TI  - Estrogen receptor-alpha and -beta are expressed throughout postnatal development
      in the rat and rabbit growth plate.
AB  - Estrogen regulates skeletal growth and promotes epiphyseal fusion. To explore the
      mechanisms underlying these effects we investigated the expression of estrogen
      receptor-alpha (ERalpha) and -beta (ERbeta) in rat and rabbit growth plates
      during postnatal development, using immunohistochemistry. Immunoreactivity for
      ERalpha and ERbeta was observed in resting zone and proliferative zone
      chondrocytes at all ages studied for both rat (7, 14, 28 and 70 days of age) and
      rabbit (1, 7, 28 and 120 days of age). In the rat distal humerus and the rabbit
      proximal tibia, expression of both receptors in the hypertrophic zone was minimal
      at early ages, increasing only at the last time point prior to epiphyseal fusion.
      Expression was rarely seen in the hypertrophic zone of the rat proximal tibia, a
      growth plate that does not fuse until late in life. Therefore, we conclude that
      ERalpha and ERbeta are both expressed in the mammalian growth plate. The temporal
      and anatomical pattern suggests that ER expression in the hypertrophic zone in
      particular may play a role in epiphyseal fusion.

PMID- 12065232
TI  - Structural analysis of the DNA-binding domain of alternatively spliced steroid
      receptors.
AB  - We have generated 24 DNA-binding domain structure models of alternatively spliced
      or mutated steroid receptor variants by homology-based modeling. Members of the
      steroid receptor family dispose of a DNA-binding domain which is built from two
      zinc fingers with a preserved sequence homology of about 90%. Data from
      crystallographic analysis of the glucocorticoid receptor DNA-binding domain are
      therefore appropriate to serve as a template structure. We inserted or deleted
      amino acid residues in order to study the structural details of the
      glucocorticoid, mineralocorticoid, and androgen receptor splice variants. The
      receptor variants are created by QUANTA- and MODELLER-based modeling.
      Subsequently, the resulting energy-minimized models were compared with each other
      and with the wild-type receptor respectively. A prediction for the receptor
      function based mainly on the preservation or destruction of secondary structures
      has been carried out. The simulations showed that amino acid insertions of one,
      four or nine additional residues of existing steroid receptor splice variants
      were tolerated without destruction of the secondary structure. In contrast, a
      deletion of four amino acids at the splice site junction leads to modifications
      in the secondary structure of the DNA-recognition helix which apparently disturb
      the receptor-DNA interaction. Furthermore, an insertion of 23 amino acid residues
      between the zinc finger of the androgen receptor leads to a large loop with an
      additional alpha-helical structure which seems to disconnect a specific contact
      from its hormone response element. Thereafter, the prediction of receptor
      function based on the molecular models was compared with the available
      experimental results from the in vitro function tests. We obtained a close
      correspondence between the molecular modeling-based predictions and the
      conclusions of receptor function drawn from in vitro studies.

PMID- 12065231
TI  - 6-Carboxymethyl genistein: a novel selective oestrogen receptor modulator (SERM)
      with unique, differential effects on the vasculature, bone and uterus.
AB  - The novel genistein (G) derivative, 6-carboxymethyl genistein (CG) was evaluated
      for its biological properties in comparison with G. Both compounds showed
      oestrogenic activity in vitro and in vivo. On the other hand G and CG differed in
      the following parameters: (i) only CG displayed mixed agonist-antagonist activity
      for oestrogen receptor (ER) alpha in transactivation assays and (ii) only CG was
      capable of attenuating oestrogen (E(2))-induced proliferation in vascular smooth
      muscle cells and of inhibiting oestrogen-induced creatine kinase (CK) specific
      activity in rat tissues. On the other hand only G enhanced the stimulatory effect
      on CK specific activity in the uterus. In comparison to the selective oestrogen
      receptor modulator (SERM) raloxifene (RAL), CG showed the same selectivity
      profile as RAL in blocking the CK response to E(2) in tissues derived from both
      immature and ovariectomized female rats. Molecular modelling of CG bound to the
      ligand binding domain (LBD) of ERbeta predicts that the 6-carboxymethyl group of
      CG almost fits the binding cavity. On the other hand, molecular modelling of CG
      bound to the LBD of ERalpha suggests that the carboxyl group of CG may perturb
      the end of Helix 11, eliciting a severe backbone change for Leu 525, and
      consequently induces a conformational change which could position Helix 12 in an
      antagonist conformation. This model supports the experimental findings that CG
      can act as a mixed agonist-antagonist when E(2) is bound to its receptors.
      Collectively, our findings suggest that CG can be considered a novel SERM with
      unique effects on the vasculature, bone and uterus.

PMID- 12065233
TI  - SALL1 expression in the human pituitary-adrenal/gonadal axis.
AB  - SALL1 was originally identified on the basis of its DNA sequence homology to the
      region-specific homeotic gene Sal, in Drosophila melanogaster, which acts as a
      downstream target of hedgehog/tumor growth factor-beta-like decapentaplegic
      signals. The SALL1 gene has been associated with the Townes-Brocks Syndrome
      (TBS), a disorder characterized by multiorgan dysgenesis including renal and
      genital malformations. In this study, SALL1 message production was evaluated in
      association with the tissue localization of the protein product of SALL1, p140.
      SALL1 protein expression was observed in various adult and fetal tissues which
      elaborate reproductive endocrine hormones. The p140 was localized in specific
      microanatomic sites of the pituitary, adrenal cortex and the placenta. In the
      human pituitary, SALL1 protein expression was limited to the adenohypophysis,
      where it colocalized to those cells producing GH and the gonadotropins, LH and
      FSH. SALL1 expression was also found in most of the fetal and adult adrenal
      cortex in addition to the trophoblastic cells of the placenta. This pattern of
      expression complements prior studies demonstrating p140 in testicular fetal
      Leydig cells, adult Leydig and Sertoli cells, and granulosa cells of the ovary.
      The SALL1 protein was also shown here to be highly expressed in trophoblast
      tumors, which overproduce sex hormones. The expression patterns of SALL1 at
      multiple levels of the reproductive endocrine axis and the phenotypic effects
      associated with TBS suggest that SALL1 may have an important role in the
      interaction of the pituitary-adrenal/gonadal axis during reproduction.

PMID- 12065234
TI  - Maternal undernutrition alters triiodothyronine concentrations and pituitary
      response to GnRH in fetal sheep.
AB  - The aims of this study were to determine which hormones may have a role in the
      expression of maternal undernutrition effects on reproductive function, in both
      the developing fetus and the adult offspring. This was undertaken by measuring
      the effects of long-term maternal undernutrition on metabolic hormone profiles
      and pituitary responses to single doses of GnRH and GH-releasing factor (GRF) in
      fetal sheep. From mating, groups of ewes were fed rations providing either 100%
      (HIGH) or 50% (LOW) of estimated metabolisable energy requirements for pregnancy
      throughout the experiment until slaughter at approximately 119 days of gestation.
      Fetal and maternal blood samples were collected from 113 until 119 days of
      gestation, via carotid and jugular catheters respectively, and assayed for
      insulin, IGF-I, GH, thyroxine and triiodothyronine (T(3)). Undernutrition had no
      effects on fetal weight, fetal gonad weight of either sex, fetal insulin or IGF-I
      concentrations. Male LOW fetuses exhibited a significantly attenuated response
      (P<0.05) to a bolus challenge of GnRH compared with HIGH fetuses. Basal fetal GH
      concentrations and the response to exogenous GRF were similar in both treatment
      groups, although LOW fetuses exhibited more secretory episodes (P<0.01). Mean
      T(3) concentrations were significantly lower in both the maternal (P<0.01) and
      fetal (P<0.05) plasma of LOW animals compared with HIGH animals. It is concluded
      that pituitary function was altered in fetal males and could influence male
      reproductive development. On the other hand, in female sheep, fetal gonadal
      abnormalities and reductions in reproductive capacity in adult life which are
      associated with fetal undernutrition are unlikely to be attributable to altered
      pituitary function. Additionally, these studies raise the possibility that
      thyroid hormones may have a role in the expression of maternal undernutrition
      effects on fetal development.

PMID- 12065235
TI  - NFkappaB1 (p50)-deficient mice are not susceptible to multiple low-dose
      streptozotocin-induced diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a disease characterized by the
      autoimmune destruction of the pancreatic beta-cells, which requires the
      expression of a number of immune-related genes including major histocompatibility
      complex proteins, cytokines, chemokines, and cytotoxic enzymes, many of which are
      regulated by the transcription factor, NFkappaB. Inhibition of the entire
      NFkappaB family of transcription factors may be harmful, as these factors are
      involved in many normal physiological processes. However, identifying and
      targeting specific NFkappaB subunits critical for the pathogenesis of disease may
      prove to be valuable in designing new therapeutic strategies. To assess the
      potential role of the NFkappaB subunit, p50, in the development of IDDM, mice
      with gene disruption for NFkappaB (p50) were investigated for susceptibility to
      IDDM. We found that p50-deficient mice were fully resistant against multiple low
      dose streptozotocin-induced diabetes, a model of diabetes with a strong
      autoimmune component. The site of involvement of NFkappaB (p50) lies at an early,
      critical juncture of immune activation and proinflammatory mediator production,
      because: (1) isolated islets of Langerhans from NFkappaB (p50)-deficient mice
      were not protected from the islet dysfunction induced by in vitro application of
      proinflammatory cytokines; (2) p50-deficient mice were not resistant to diabetes
      induced by a single high dose of streptozotocin, a model with a large oxidant
      component and no autoimmune involvement; and (3) diabetes induced up-regulation
      of nitric oxide and interleukin-12 was blocked in the p50-deficient mice. Our
      data suggest that NFkappaB (p50) has an essential role in the development of
      autoimmune diabetes. Selective therapeutic blockade of this subunit may be
      beneficial in preventing IDDM.

PMID- 12065236
TI  - Glucagon-like peptide-1 (GLP-1) and glucose metabolism in human myocytes.
AB  - Glucagon-like peptide-1 (GLP-1) has been shown to have insulin-like effects upon
      the metabolism of glucose in rat liver, muscle and fat, and on that of lipids in
      rat and human adipocytes. These actions seem to be exerted through specific
      receptors which, unlike that of the pancreas, are not - at least in liver and
      muscle - cAMP-associated. Here we have investigated the effect, its
      characteristics, and possible second messengers of GLP-1 on the glucose
      metabolism of human skeletal muscle, in tissue strips and primary cultured
      myocytes. In muscle strips, GLP-1, like insulin, stimulated glycogen synthesis,
      glycogen synthase a activity, and glucose oxidation and utilization, and
      inhibited glycogen phosphorylase a activity, all of this at physiological
      concentrations of the peptide. In cultured myotubes, GLP-1 exerted, from 10(-13)
      mol/l, a dose-related increase of the D-[U-(14)C]glucose incorporation into
      glycogen, with the same potency as insulin, together with an activation of
      glycogen synthase a; the effect of 10(-11) mol/l GLP-1 on both parameters was
      additive to that induced by the equimolar amount of insulin. Synthase a was still
      activated in cells after 2 days of exposure to GLP-1, as compared with myotubes
      maintained in the absence of peptide. In human muscle cells, exendin-4 and its
      truncated form 9-39 amide (Ex-9) are both agonists of the GLP-1 effect on
      glycogen synthesis and synthase a activity; but while neither GLP-1 nor exendin-4
      affected the cellular cAMP content after 5-min incubation in the absence of 3
      isobutyl-1-methylxantine (IBMX), an increase was detected with Ex-9. GLP-1,
      exendin-4, Ex-9 and insulin all induced the prompt hydrolysis of
      glycosylphosphatidylinositols (GPIs). This work shows a potent stimulatory effect
      of GLP-1 on the glucose metabolism of human skeletal muscle, and supports the
      long-term therapeutic value of the peptide. Further evidence for a GLP-1 receptor
      in this tissue, different from that of the pancreas, is also illustrated,
      suggesting a role for an inositolphosphoglycan (IPG) as at least one of the
      possible second messengers of the GLP-1 action in human muscle.

PMID- 12065237
TI  - Thyroid follicular cells secrete plasminogen activators and can form angiostatin
      from plasminogen.
AB  - Angiostatin, a 38 kDa fragment of plasminogen, potently inhibits the growth of
      blood vessels. Angiostatin is generated from plasminogen by urokinase-type (uPA)
      and tissue-type (tPA) plasminogen activators in the presence of free sulphydryl
      donors. Angiogenesis inhibitors may be important in regulating angiogenesis in
      developing goitre. We have examined angiostatin formation in human primary
      thyrocyte cultures and a rat thyrocyte cell line (FRTL-5). We found that human
      thyroid cells in culture secrete plasminogen activators (both tPA and uPA) as
      well as matrix metalloproteinase 2 into the medium. When human thyrocyte
      conditioned medium was incubated with plasminogen (10 microg/ml) and N
      acetylcysteine (100 microM) for 24 h, a 38 kDa fragment of plasminogen, which is
      consistent with angiostatin, was generated. The appearance of the 38 kDa fragment
      was increased by agents that increase cAMP (forskolin and 8 BrcAMP). FRTL-5
      cells, which do not secrete uPA or tPA, did not generate angiostatin. Thyroid
      cells produce several angiogenic growth factors, and human thyrocyte conditioned
      medium stimulated growth of endothelial cells. When the conditioned medium was
      incubated with plasminogen and N-acetylcysteine, this stimulatory effect was
      lost, consistent with the production of a growth inhibitory factor. We conclude
      that thyroid cells can produce angiostatin from plasminogen in vitro, and this
      may play a role in vivo in limiting goitre size.

PMID- 12065238
TI  - Immunomodulatory effects of prolactin and growth hormone in the tilapia,
      Oreochromis mossambicus.
AB  - To clarify the roles of prolactin (PRL) and GH in the control of the immune
      system, the effects of environmental salinity, hypophysectomy, and PRL and GH
      administration on several immune functions were examined in tilapia (Oreochromis
      mossambicus). Transfer from fresh water (FW) to seawater (SW) did not alter
      plasma levels of immunoglobulin M (IgM) and lysozyme. The superoxide anion (O(2)(
      )) production in head kidney leucocytes accompanied by phagocytosis was elevated
      in SW-acclimated fish over the levels observed in FW fish. Hypophysectomy of the
      fish in FW resulted in a reduction in O(2)(-) production in leucocytes isolated
      from the head kidney, whereas there was no significant change in plasma levels of
      IgM or lysozyme. Treatment with tilapia GH and PRLs (PRL(177) and PRL(188))
      enhanced O(2)(-) production in vitro in head kidney leucocytes in a dose-related
      manner. Extrapituitary expression of two PRLs, GH and IGF-I mRNA was detected in
      lymphoid tissues and cells such as head kidney, spleen, intestine and leucocytes
      from peripheral blood and head kidney. PRL-receptor mRNA was detected in head
      kidney leucocytes, and the level of expression was higher in SW-acclimated fish
      than that in FW fish. Treatment with PRL(177) caused higher production of O(2)(-)
      in the head kidney leucocytes isolated from SW tilapia than that from FW fish. In
      view of the fact that PRL acts antagonistically to osmoregulation in SW, its
      immunomodulatory actions in this euryhaline fish would appear to be independent
      of its osmoregulatory action.

PMID- 12065239
TI  - Implication of alpha4 phosphoprotein and the rapamycin-sensitive mammalian target
      of-rapamycin pathway in prolactin receptor signalling.
AB  - A prolactin (PRL)-responsive 3'-end cDNA encoding rat alpha4 phosphoprotein was
      previously isolated from a rat lymphoma cDNA library. Rat alpha4 is a homologue
      of yeast Tap42 and is a component of the mammalian target-of-rapamycin (mTOR)
      signalling pathway that stimulates translation initiation and G1 progression in
      response to nutrients and growth factors. In the present study, the full-length
      rat alpha4 cDNA was obtained by 5'-RACE and the 1023 bp open reading frame
      predicted a 340 amino acid protein of 39.1 kDa. The alpha4 mRNA was expressed in
      quiescent PRL-dependent Nb2 lymphoma cells deprived of PRL for up to 72 h but
      expression was downregulated within 4 h of PRL treatment. In contrast, PRL
      independent Nb2-Sp cells showed constitutive expression of alpha4 that was not
      affected by PRL. Western analysis of Nb2 cell lysates or of V5-tagged-alpha4
      expressed in COS-1 cells detected a single immunoreactive band of approximately
      45 kDa. Enzymatic deglycosylation of affinity-purified 45 kDa alpha4 yielded the
      predicted 39 kDa protein. Phosphorylation of Nb2 alpha4 was induced by PRL or 2-O
      tetradecanoyl-phorbol-13-acetate (TPA) and further enhanced by a combination of
      PRL and TPA. The Nb2 alpha4 associated with the catalytic subunit of protein
      phosphatase 2A and localized predominantly in Nb2 nuclear fractions with trace
      amounts in the cytosol. The immunosuppressant drug rapamycin inhibited
      proliferation of Nb2 cells in response to PRL or interleukin-2, but had no effect
      on Nb2-Sp cells. Furthermore, transient overexpression of alpha4 in COS-1 cells
      inhibited PRL stimulation of the immediate-early gene interferon regulatory
      factor-1 promoter activity. Therefore, PRL downregulation of alpha4 expression
      and/or PRL-inducible phosphorylation of alpha4 may be necessary for PRL receptor
      (PRLr) signalling to the interferon regulatory factor-1 promoter in the Nb2 cells
      and, furthermore, implicates cross-talk between the mTOR and PRLr signalling
      cascades during Nb2 cell mitogenesis.

PMID- 12065240
TI  - Plasma growth hormone and growth hormone-binding protein during development in
      the marsupial brushtail possum (Trichosurus vulpecula).
AB  - Plasma concentrations of growth hormone (GH) were measured in the brushtail
      possum (Trichosurus vulpecula) pouch young from 25 through to 198 days post
      partum (n=71). GH concentrations were highest early in pouch life (around 100
      ng/ml), and thereafter declined in an exponential fashion to reach adult
      concentrations (10.8+/-1.8 ng/ml; n=21) by approximately 121-145 days post
      partum, one to two months before the young is weaned. Growth hormone-binding
      protein (GHBP), which has been shown to modify the cellular actions of GH in
      eutherian mammals, was identified for the first time in a marsupial. Based on
      size exclusion gel filtration, possum GHBP had an estimated molecular mass of
      approximately 65 kDa, similar to that identified in other mammalian species, and
      binding of (125)I-labelled human GH (hGH) was displaced by excess hGH (20
      microg). An immunoprecipitation method, in which plasma GHBP was rendered
      polyethylene glycol precipitable with a monoclonal antibody to the rabbit GHBP/GH
      receptor (MAb 43) and labelled with (125)I-hGH, was used to quantitate plasma
      GHBP by Scatchard analysis in the developing (pooled plasma samples) and adult
      (individual animals) possums. Binding affinity (K(a)) values in pouch young aged
      between 45 and 54 and 144 and 153 days post-partum varied between 1.0 and 2.4 x
      10(9)/M, which was slightly higher than that in adult plasma (0.96+/-0.2 x
      10(9)/M, n=6). Binding capacity (B(max)) values increased from non-detectable
      levels in animals aged 25-38 days post-partum to reach concentrations around half
      that seen in the adult (1.4+/-0.2 x 10(-9) M) by about 117 days post-partum and
      remained at this level until 153 days post-partum. Therefore, in early pouch life
      when plasma GH concentrations are highest, the very low concentrations of GHBP
      are unlikely to be important in terms of competing with GH-receptor for ligand or
      altering the half-life of circulating GH.

PMID- 12065241
TI  - Food conversion is transiently affected during 4-week chronic administration of
      melanocortin agonist and antagonist in rats.
AB  - The central melanocortin system is involved in the regulation of food intake and
      body weight. In this study, we investigated the effect of a 4-week
      intracerebroventricular infusion of the melanocortin receptor agonist MT-II and
      the selective melanocortin-4 receptor antagonist HS024 on food intake and body
      weight homeostasis. The MT-II-treated rats ate less and lost considerably more
      weight than the control rats during the first week of treatment. During the
      second and third week, they gained weight and, by the end of the treatment
      period, the weight gain was similar to that of the control rats. The HS024
      treatment caused hyperphagia and development of obesity during the entire period.
      Extensive accumulations of fat and a sixfold increase in leptin levels were
      observed in the HS024-treated rats, as compared with controls, after the 4-week
      period. Food conversion ratio, defined as body weight increase relative to weight
      of ingested food, was clearly increased in the HS024-treated rats, while it was
      lowered in the MT-II-treated rats compared with controls. The effect on food
      conversion ratio was transient, being greatest for both experimental groups
      during the first week and it was then attenuated to reach the level of controls
      at the end of the study. The results suggest that long-term injection of
      exogenous melanocortin receptor active substances may have an important transient
      effect on food conversion.

PMID- 12065242
TI  - Vitamin D inhibits the activation of stress-activated protein kinases by
      physiological and environmental stresses in keratinocytes.
AB  - In addition to its known effects on keratinocyte proliferation and
      differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and
      chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery
      needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the
      stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK)
      and p38, is an early cellular response to stress signals and an important
      determinant of cell fate. This study examines whether modulation of these SAPKs
      is associated with the effects of 1,25(OH)(2)D(3) on keratinocytes under stress.
      HaCaT keratinocytes were exposed to heat shock, hyperosmotic concentrations of
      sorbitol, the epidermal growth factor receptor tyrosine kinase inhibitor AG1487,
      the pro-inflammatory cytokine tumor necrosis factor alpha, and H(2)O(2). These
      stresses activated both SAPKs. Pretreatment with 1,25(OH)(2)D(3) inhibited the
      activation of JNK by all stresses and the activation of p38 by heat shock, AG1478
      and tumor necrosis factor alpha. Under the same conditions, treatment with
      1,25(OH)(2)D(3) protected HaCaT keratinocytes from cytotoxicity induced by
      exposure to H(2)O(2) and hyperosmotic shock. The effect of 1,25(OH)(2)D(3) was
      dose-dependent, already apparent at nanomolar concentrations, and time-dependent,
      maximal after a 24-h pre-incubation. We suggest that inhibition of SAPK
      activation may account for some of the well-documented protective effects of
      1,25(OH)(2)D(3) on epidermal cells during exposure to UV or chemotherapy and may
      also be related to the anti-inflammatory actions of the hormone in skin.

PMID- 12065243
TI  - Calcium inhibits ovarian steroidogenesis in the blowfly Phormia regina.
AB  - Calcium is frequently involved in the stimulation of steroidogenesis in gonads
      and endocrine glands, generally in association with cAMP. However, our present
      observations show that it has the opposite effect in the ovary of the blowfly
      Phormia regina. Our in vitro experiments first showed that extracellular calcium
      does not play a role during the stimulation of steroidogenesis in fly ovaries;
      indeed steroidogenesis was activated in vitro as efficiently in a medium with or
      without calcium, either by pharmacological compounds mimicking cAMP signaling or
      by active brain extracts. When calcium was experimentally introduced into
      biosynthetic cells by ionophores or liberated from internal stores by
      thapsigargin, it did not activate, but clearly inhibited both basal and acute
      steroidogenesis respectively in previtellogenic and in vitellogenic ovaries. Our
      experiments also demonstrated that calcium decreases cAMP concentrations in the
      ovaries of Phormia, by stimulating its degradation, without modifying its
      biosynthesis. Moreover, inhibitors of calcium-calmodulin phosphodiesterases
      (PDEs) increased steroid biosynthesis in vitro, whereas inhibitors of calcium
      insensitive PDEs did not. These data thus demonstrate that, in blowfly ovaries,
      calcium ions inhibit cAMP-stimulated steroidogenesis by activating a calmodulin
      sensitive (type I) PDE.

PMID- 12065244
TI  - Insulin-like growth factor binding protein-related protein 1 inhibits
      proliferation of MCF-7 breast cancer cells via a senescence-like mechanism.
AB  - Elevated insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1)
      mRNA in senescent human mammary epithelial cells suggested that the IGFBP-3 gene
      product may inhibit cell proliferation. To test this hypothesis, we used a
      retroviral vector to express IGFBP-rP1 cDNA in the IGFBP-rP1-deficient MCF-7
      breast cancer cell line. Compared with control vector-transduced cells,
      cumulative cell numbers for IGFBP-rP1-transduced polyclonal or clonal cell
      cultures were reduced by 39 and 74%, respectively, after 1 week. Medium
      conditioned by IGFBP-rP1-producing cultures reduced cumulative cell numbers in
      parental MCF-7 cultures by 20% compared with medium from cultures of a control
      vector-transduced cell line. Nuclear fragmentation analysis and cell
      proliferation assays completed in the presence of the pan-caspase inhibitor
      benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone excluded apoptosis as the
      responsible mechanism. The percentage of cells containing senescence-associated
      beta-galactosidase activity was doubled compared with control cell cultures. Flow
      cytometry analysis indicated that twice as many noncycling cells were present in
      the IGFBP-rP1-transduced MCF-7 cell cultures compared with controls. These
      findings indicate that IGFBP-rP1 is an inhibitor of MCF-7 breast cancer cell
      proliferation and may act via a cellular senescence-like mechanism.

PMID- 12065245
TI  - Specificity of E2F1, E2F2, and E2F3 in mediating phenotypes induced by loss of
      Rb.
AB  - The Rb/E2F pathway plays a critical role in the control ofcellular proliferation.
      Here, we report that E2F1, E2F2, and E2F3 make major individual contributions
      toward the in vivo phenotypic consequences of Rb deficiency. In the developing
      lens of Rb(-/-) embryos, loss of E2F1, E2F2, or E2F3 reduces the unscheduled
      proliferation of fiber cells, with the loss of E2F3 having the most pronounced
      effect. In Rb-deficient retinas, all three E2Fs contribute equally to the ectopic
      proliferation of postmitotic neuronal cells. In contrast, E2F1 is unique in
      mediating apoptosis in both Rb(-/-) lenses and retinas. In the central nervous
      system, loss of E2F1 or E2F3 can almost completely eliminate the ectopic DNA
      replication and apoptosis observed in Rb(-/-) embryos, and loss of E2F2 partially
      reduces the unscheduled DNA replication and has no effect on apoptosis. These
      results provide clear evidence for functional specificity among E2Fs in the
      control of Rb-dependent proliferation and apoptosis in a tissue-specific manner.

PMID- 12065246
TI  - 10-formyltetrahydrofolate dehydrogenase, one of the major folate enzymes, is down
      regulated in tumor tissues and possesses suppressor effects on cancer cells.
AB  - Our studies showed that an abundant folate enzyme, 10
      formyltetrahydrofolatedehydrogenase (FDH), is strongly down-regulated in several
      types of cancer on both the mRNA and the protein level. Transient expression of
      FDH in several human prostate cancer cell lines, a hepatocarcinoma cell line,
      HepG2, and a lung cancer cell line, A549, suppressed proliferation and resulted
      in cytotoxicity. In contrast, overexpression of a catalytically inactive FDH
      mutant did not inhibit proliferation, which suggests that the suppressor effect
      of FDH is a result of its enzymatic function. Because the FDH substrate, 10
      formyltetrahydrofolate, is required for de novo purine biosynthesis, we
      hypothesized that the inhibitory effects of FDH occur through the depletion of
      intracellular 10-formyltetrahydrofolate followed by the loss of de novo purine
      biosynthesis. The ultimate impact is diminished DNA/RNA biosynthesis. Indeed,
      supplementation of FDH-overexpressing cells with 5-formyltetrahydrofolate or
      hypoxanthine reversed the FDH growth-inhibitory effects. Hence, down-regulation
      of FDH in tumors is proposed to be one of the cellular mechanisms that enhance
      proliferation.

PMID- 12065247
TI  - Protein kinase Cdelta overexpression enhances radiation sensitivity via
      extracellular regulated protein kinase 1/2 activation, abolishing the radiation
      induced G(2)-M arrest.
AB  - Protein kinase C (PKC) has been widely implicated in regulation ofcell
      growth/cell cycle progression and apoptosis. However,the role of PKCdelta in
      radiosensitivity and cell cycle regulation remains unclear. Overexpression of
      PKCdelta increased Ca2+-independent PKC activity without altering other PKC
      isoforms (PKCalpha, -beta1, -epsilon, and -zeta), and extracellular regulated
      protein kinase (ERK) 1/2 activity was also increased in PKCdelta-specific manner.
      A clonogenic survival assay showed that PKCdelta-overexpressed cells had more
      radiosensitivity and pronounced induction of apoptosis than control cells. Flow
      cytometric analysis revealed that PKCdelta made the cells escape from radiation
      induced G(2)-M arrest. Moreover, p53 and p21(Waf) induction by radiation were
      higher in PKCdelta-overexpressed cells than control cells, and PKCdelta-mediated
      apoptosis was reduced, when radiation-induced ERK1/2 activity was inhibited by
      PD98059. Furthermore, PKCdelta antisense and rottlerin, PKC inhibitor-abrogated
      PKCdelta-mediated radiosensitivity and reduced ERK1/2 activity to the control
      vector level. These results demonstrated that PKCdelta overexpression enhanced
      radiation-induced apoptosis and radiosensitivity via ERK1/2 activation, thereby
      abolishing the radiation-induced G(2)-M arrest and finally apoptosis.

PMID- 12065248
TI  - Thinking the unthinkable!

PMID- 12065249
TI  - Oxygen therapy in acute medical care.

PMID- 12065250
TI  - Adoption by lesbian couples.

PMID- 12065251
TI  - Forensic pathology services.

PMID- 12065252
TI  - Our favourite drug.

PMID- 12065253
TI  - Lack of progress at summit spells disaster for poor countries.

PMID- 12065254
TI  - Negligence settlements in England increase sevenfold in five years.

PMID- 12065256
TI  - Gene responsible for most malignant melanomas is discovered.

PMID- 12065257
TI  - Doctors in India and Pakistan campaign against nuclear war.

PMID- 12065259
TI  - NICE guidance "a real victory" for people with schizophrenia. National Institute
      for Clinical Excellence.

PMID- 12065260
TI  - UK pill compensation claim collapses.

PMID- 12065261
TI  - Changing hearts and minds.

PMID- 12065262
TI  - Quality of life measurement: bibliographic study of patient assessed health
      outcome measures.
AB  - OBJECTIVES: To assess the growth of quality of life measures and to examine the
      availability of measures across specialties. DESIGN: Systematic searches of
      electronic databases to identify developmental and evaluative work relating to
      health outcome measures assessed by patients. MAIN OUTCOME MEASURES: Types of
      measures: disease or population specific, dimension specific, generic,
      individualised, and utility. Specialties in which measures have been developed
      and evaluated. RESULTS: 3921 reports that described the development and
      evaluation of patient assessed measures met the inclusion criteria. Of those that
      were classifiable, 1819 (46%) were disease or population specific, 865 (22%) were
      generic, 690 (18%) were dimension specific, 409 (10%) were utility, and 62 (1%)
      were individualised measures. During 1990-9 the number of new reports of
      development and evaluation rose from 144 to 650 per year. Reports of disease
      specific measures rose exponentially. Over 30% of evaluations were in cancer,
      rheumatology and musculoskeletal disorders, and older people's health. The
      generic measures--SF-36, sickness impact profile, and Nottingham health profile-
      accounted for 612 (16%) reports. CONCLUSIONS: In some specialties there are
      numerous measures of quality of life and little standardisation. Primary research
      through the concurrent evaluation of measures and secondary research through
      structured reviews of measures are prerequisites for standardisation.
      Recommendations for the selection of patient assessed measures of health outcome
      are needed.

PMID- 12065263
TI  - Stressful life experiences and risk of relapse of breast cancer: observational
      cohort study.
AB  - OBJECTIVE: To confirm, using an observational cohort design, the relation between
      severely stressful life experiences and relapse of breast cancer found in a
      previous case-control study. DESIGN: Prospective follow up for five years of a
      cohort of women newly diagnosed as having breast cancer, collecting data on
      stressful life experiences, depression, and biological prognostic factors.
      SETTING: NHS breast clinic, London; 1991-9. PARTICIPANTS: A consecutive series of
      women aged under 60 newly diagnosed as having a primary operable breast tumour.
      202/222 (91%) eligible women participated in the first life experiences
      interview. 170 (77%) provided complete interview data either up to 5 years after
      diagnosis or to recurrence. MAIN OUTCOME MEASURE: Recurrence of disease. RESULTS:
      We controlled for biological prognostic factors (lymph node infiltration and
      tumour histology), and found no increased risk of recurrence in women who had had
      one or more severely stressful life experiences in the year before diagnosis
      compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58
      to 1.74, P=0.99). Women who had had one or more severely stressful life
      experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52,
      0.29 to 0.95, P=0.03) than those who did not. CONCLUSION: These data do not
      confirm an earlier finding from a case-control study that severely stressful life
      experiences increase the risk of recurrence of breast cancer. Differences in case
      control and prospective methods may explain the contradictory results. We took
      the prospective study as the more robust, and the results suggest that women with
      breast cancer need not fear that stressful experiences will precipitate the
      return of their disease.

PMID- 12065264
TI  - Impact of preventive strategies on trend of occupational skin disease in
      hairdressers: population based register study.

PMID- 12065265
TI  - Postmortem examinations using magnetic resonance imaging: four year review of a
      working service.

PMID- 12065266
TI  - Rising incidence of Kawasaki disease in England: analysis of hospital admission
      data.

PMID- 12065267
TI  - Interventions to reduce unintended pregnancies among adolescents: systematic
      review of randomised controlled trials.
AB  - OBJECTIVE: To review the effectiveness of primary prevention strategies aimed at
      delaying sexual intercourse, improving use of birth control, and reducing
      incidence of unintended pregnancy in adolescents. DATA SOURCES: 12 electronic
      bibliographic databases, 10 key journals, citations of relevant articles, and
      contact with authors. STUDY SELECTION: 26 trials described in 22 published and
      unpublished reports that randomised adolescents to an intervention or a control
      group (alternate intervention or nothing). DATA EXTRACTION: Two independent
      reviewers assessed methodological quality and abstracted data. DATA SYNTHESIS:
      The interventions did not delay initiation of sexual intercourse in young women
      (pooled odds ratio 1.12; 95% confidence interval 0.96 to 1.30) or young men
      (0.99; 0.84 to 1.16); did not improve use of birth control by young women at
      every intercourse (0.95; 0.69 to 1.30) or at last intercourse (1.05; 0.50 to
      2.19) or by young men at every intercourse (0.90; 0.70 to 1.16) or at last
      intercourse (1.25; 0.99 to 1.59); and did not reduce pregnancy rates in young
      women (1.04; 0.78 to 1.40). Four abstinence programmes and one school based sex
      education programme were associated with an increase in number of pregnancies
      among partners of young male participants (1.54; 1.03 to 2.29). There were
      significantly fewer pregnancies in young women who received a multifaceted
      programme (0.41; 0.20 to 0.83), though baseline differences in this study
      favoured the intervention. CONCLUSIONS: Primary prevention strategies evaluated
      to date do not delay the initiation of sexual intercourse, improve use of birth
      control among young men and women, or reduce the number of pregnancies in young
      women.

PMID- 12065268
TI  - Limits of teacher delivered sex education: interim behavioural outcomes from
      randomised trial.
AB  - OBJECTIVE: To determine whether a theoretically based sex education programme for
      adolescents (SHARE) delivered by teachers reduced unsafe sexual intercourse
      compared with current practice. DESIGN: Cluster randomised trial with follow up
      two years after baseline (six months after intervention). A process evaluation
      investigated the delivery of sex education and broader features of each school.
      SETTING: Twenty five secondary schools in east Scotland. PARTICIPANTS: 8430
      pupils aged 13-15 years; 7616 completed the baseline questionnaire and 5854
      completed the two year follow up questionnaire. INTERVENTION: SHARE programme
      (intervention group) versus existing sex education (control programme). MAIN
      OUTCOME MEASURES: Self reported exposure to sexually transmitted disease, use of
      condoms and contraceptives at first and most recent sexual intercourse, and
      unwanted pregnancies. RESULTS: When the intervention group was compared with the
      conventional sex education group in an intention to treat analysis there were no
      differences in sexual activity or sexual risk taking by the age of 16 years.
      However, those in the intervention group reported less regret of first sexual
      intercourse with most recent partner (young men 9.9% difference, 95% confidence
      interval -18.7 to -1.0; young women 7.7% difference, -16.6 to 1.2). Pupils
      evaluated the intervention programme more positively, and their knowledge of
      sexual health improved. Lack of behavioural effect could not be linked to
      differential quality of delivery of intervention. CONCLUSIONS: Compared with
      conventional sex education this specially designed intervention did not reduce
      sexual risk taking in adolescents.

PMID- 12065269
TI  - Systematic review of cost effectiveness studies of telemedicine interventions.
AB  - OBJECTIVES: To systematically review cost benefit studies of telemedicine.
      DESIGN: Systematic review of English language, peer reviewed journal articles.
      DATA SOURCES: Searches of Medline, Embase, ISI citation indexes, and database of
      Telemedicine Information Exchange. STUDIES SELECTED: 55 of 612 identified
      articles that presented actual cost benefit data. MAIN OUTCOME MEASURES:
      Scientific quality of reports assessed by use of an established instrument for
      adjudicating on the quality of economic analyses. RESULTS: 557 articles without
      cost data categorised by topic. 55 articles with data initially categorised by
      cost variables employed in the study and conclusions. Only 24/55 (44%) studies
      met quality criteria justifying inclusion in a quality review. 20/24 (83%)
      restricted to simple cost comparisons. No study used cost utility analysis, the
      conventional means of establishing the "value for money" that a therapeutic
      intervention represents. Only 7/24 (29%) studies attempted to explore the level
      of utilisation that would be needed for telemedicine services to compare
      favourably with traditionally organised health care. None addressed this question
      in sufficient detail to adequately answer it. 15/24 (62.5%) of articles reviewed
      here provided no details of sensitivity analysis, a method all economic analyses
      should incorporate. CONCLUSION: There is no good evidence that telemedicine is a
      cost effective means of delivering health care.

PMID- 12065271
TI  - Death from tetanus after a pretibial laceration.

PMID- 12065270
TI  - Nutritional genomics.

PMID- 12065272
TI  - Improving child health: the role of research.

PMID- 12065273
TI  - Randomised trials in surgery: problems and possible solutions.

PMID- 12065274
TI  - Unhappy doctors. Medical education must reassert its claim to academic high
      ground.

PMID- 12065275
TI  - Nurses need more resources to do their job.

PMID- 12065276
TI  - BMA negotiator calls for more male medical students. Working women seem to be
      scapegoats in medicine.

PMID- 12065277
TI  - Access to invasive procedures can be audited by ethnic group.

PMID- 12065278
TI  - Hip protectors. Carpets can be used to reduce injury from falls.

PMID- 12065279
TI  - Cardiothoracic surgeons do a good job.

PMID- 12065280
TI  - Informaticist services for policymakers will differ from those studied.

PMID- 12065281
TI  - Attitudes towards general practice are changing.

PMID- 12065282
TI  - Animal models can assist medicine in humans.

PMID- 12065284
TI  - Expert shows how pens should be held.

PMID- 12065283
TI  - Staphylococci are unlikely to cause acute dental infections.

PMID- 12065285
TI  - The epithelial cell cytoskeleton and intracellular trafficking. I. Shiga toxin B
      subunit system: retrograde transport, intracellular vectorization, and more.
AB  - Many intracellular transport routes are still little explored. This is
      particularly true for retrograde transport between the plasma membrane and the
      endoplasmic reticulum. Shiga toxin B subunit has become a powerful tool to study
      this pathway, and recent advances on the molecular mechanisms of transport in the
      retrograde route and on its physiological function(s) are summarized.
      Furthermore, it is discussed how the study of retrograde transport of Shiga toxin
      B subunit allows one to design new methods for the intracellular delivery of
      therapeutic compounds.

PMID- 12065286
TI  - Physiology and pathophysiology of the interstitial cells of Cajal: from bench to
      bedside. VI. Pathogenesis and therapeutic approaches to human gastric
      dysrhythmias.
AB  - This review describes recent advances in our knowledge about the pathogenesis and
      therapeutic approaches to human gastric dysrhythmias. A number of clinical
      conditions has been found to be associated with gastric slow-wave rhythm
      disturbances that may relate to the induction of nausea and vomiting. Human and
      animal studies indicate that multiple neurohumoral factors are involved in the
      generation of gastric dysrhythmias. Antral distension and increased intestinal
      delivery of lipids may cause slow-wave disruption and development of nausea. This
      may be mediated by cholinergic and serotonergic pathways. Similarly, progesterone
      and estrogen may also disrupt gastric slow-wave rhythm in susceptible
      individuals. Prostaglandin overproduction in gastric smooth muscle appears to
      mediate slow-wave disruption in diabetes and with tobacco smoking. On the other
      hand, central cholinergic pathways play an important role in the genesis of
      gastric dysrhythmias associated with motion sickness. This may be mediated by
      vasopressin released from the pituitary. Although it is difficult to ascribe with
      certainty a causative role of slow-wave rhythm disturbances in the genesis of
      nausea and vomiting, the search has begun for novel antiemetic therapies based on
      their abilities to ablate or prevent gastric dysrhythmia formation. This includes
      the use of prostaglandin synthesis inhibitors, central muscarinic receptor
      antagonists, and dopamine receptor antagonists. Finally direct gastric electrical
      stimulation using a surgically implanted neurostimulator has shown promise in
      reducing emesis in patients with gastroparesis and gastric dysrhythmias.

PMID- 12065287
TI  - Biomechanics of failed deglutitive upper esophageal sphincter relaxation in
      neurogenic dysphagia.
AB  - Our aims were to examine the etiology and biomechanical properties of the
      nonrelaxing upper esophageal sphincter (UES) and the relationship between UES
      opening and failed relaxation. We examined the relationships among swallowed
      bolus volume, intrabolus pressure, sagittal UES diameter, the pharyngeal swallow
      response, and geniohyoid shortening in 18 patients with failed UES relaxation, 23
      healthy aged controls, and 15 with Zenker's diverticulum. Etiology of failed UES
      relaxation was 56% medullary disease, 33% Parkinson's or extrapyramidal disease;
      and 11% idiopathic. Extent of UES opening ranged from absent to normal and
      correlated with preservation of the pharyngeal swallow response (P = 0.012) and
      geniohyoid shortening (P = 0.046). Intrabolus pressure was significantly greater
      compared with aged controls (P < 0.001) or Zenker's diverticulum (P < 0.001). The
      bolus volume-dependent increase in intrabolus pressure evident in controls was
      not observed in failed UES relaxation. The nonrelaxing UES therefore displays a
      constant loss of sphincter compliance throughout the full, and potentially
      normal, range of expansion during opening. Adequacy of UES opening is influenced
      by the degree of preservation of the pharyngeal swallow response and hyolaryngeal
      traction. In contrast, the stenotic UES displays a static loss of compliance,
      only apparent once the limit of sphincter expansion is reached.

PMID- 12065289
TI  - Functional role of specific amino acid residues in human thiamine transporter
      SLC19A2: mutational analysis.
AB  - SLC19A2 is a membrane thiamine transporter expressed in a variety of human
      tissues, including the gastrointestinal tract. Little is currently known about
      the structure/function relationship of SLC19A2. We examined the effect of
      introducing mutations in SLC19A2 identical to those found in thiamine-responsive
      megaloblastic anemia syndrome (TRMA), on functional activity and membrane
      expression of the transporter. We also examined the effect of mutating the only
      conserved anionic residue (E138) in the transmembrane (TM) domains of the SLC19A2
      and that of the putative glycosylation sites (N63, N314). Northern blot analysis
      showed SLC19A2 mRNA was expressed at the same level in HeLa cells transfected
      with wild-type or mutated SLC19A2. Introducing the clinically relevant mutations
      (D93H, S143F, G172D) or mutation at the conserved anionic residue (E138A) of
      SLC19A2 led to a significant (P < 0.01) inhibition of thiamine uptake. Mutations
      of the two potential N-linked glycosylation sites (N63Q, N314Q) of SLC19A2 did
      not affect functional activity; they did, however, lead to a noticeable reduction
      in apparent molecular weight of protein. Western blot analysis showed all
      proteins (except D93H) were expressed in the membrane (not the cytoplasmic)
      fraction of HeLa cells. These results provide direct confirmation that clinically
      relevant mutations in SLC19A2 observed in TRMA cause malfunctioning of the
      transporter and/or a defect in its translation/stability. Results also show
      conserved TM anionic residue of the SLC19A2 protein is critical for its function.
      Furthermore, native SLC19A2 is glycosylated, but this is not important for its
      function.

PMID- 12065288
TI  - Modulatory effects of estrogen in two murine models of experimental colitis.
AB  - The association between oral contraceptives or pregnancy and inflammatory bowel
      disease is unclear. We investigated whether 17beta-estradiol modulates intestinal
      inflammation in two models of colitis. Female mice were treated with 17beta
      estradiol alone or with tamoxifen, tamoxifen alone, 17 alpha-estradiol, or
      placebo. Dinitrobenzene sulfonic acid (DNB)- or dextran sodium sulfate (DSS)
      induced colitis were assessed macroscopically, histologically, and by
      myeloperoxidase (MPO) activity. Malondialdehyde and mRNA levels of intercellular
      adhesion molecule-1 (ICAM-1), interferon-gamma (IFN-gamma), and interleukin-13
      (IL-13) were determined. In DNB colitis, 17beta-estradiol alone, but not 17beta
      estradiol plus tamoxifen, or 17 alpha-estradiol reduced macroscopic and
      histological scores, MPO activity and malondialdehyde levels. 17beta-Estradiol
      also decreased the expression of ICAM-1, IFN-gamma, and IL-13 mRNA levels
      compared with placebo. In contrast, 17beta-Estradiol increased the macroscopic
      and histological scores compared with placebo in mice with DSS colitis. These
      results demonstrate anti-inflammatory and proinflammatory effects of 17beta
      estradiol in two different models of experimental colitis. The net modulatory
      effect most likely reflects a combination of estrogen receptor-mediated effects
      and antioxidant activity and may explain, in part, conflicting results from
      clinical trials.

PMID- 12065290
TI  - Role of PP2B in cAMP-induced dephosphorylation and translocation of NTCP.
AB  - cAMP-mediated stimulation of hepatic bile acid uptake is associated with
      dephosphorylation and translocation of Na+-taurocholate (TC) cotransporting
      peptide (NTCP) to the plasma membrane. Although translocation of NTCP may be
      facilitated by dephosphorylation, the mechanism of dephosphorylation is unknown.
      The ability of cAMP to translocate and dephosphorylate NTCP is, in part,
      dependent on cAMP-mediated increases in cytosolic Ca2+ concentration ([Ca2+]),
      indicating that a Ca2+/calmodulin-dependent protein phosphatase (PP2B) may be
      involved. Thus we studied the role of PP2B using the inhibitor cypermethrin (CM).
      Freshly isolated hepatocytes were pretreated with 1-5 nM CM for 30 min followed
      by 15 min incubation with 10 microM 8-(4-chlorophenylthio)cAMP. CM (5 nM) and FK
      506 (5 microM) inhibited cAMP-stimulated TC uptake by 80 and 75%, respectively,
      without affecting basal TC uptake. CM also reversed cAMP-mediated NTCP
      dephosphorylation and translocation to 80 and 15% of the basal level,
      respectively. cAMP stimulated PP2B activity by 60%, and this effect was
      completely inhibited by 5 nM CM. PP2B dephosphorylated NTCP immunoprecipitated
      from control but not from cAMP-treated hepatocytes. The effect of CM was not due
      to any changes in cAMP-mediated increases in cytosolic [Ca2+] or decreases in
      mitogen-activated protein kinase (extracellular regulated kinases 1 and 2)
      activity. Taken together, these results suggest that cAMP dephosphorylates NTCP
      by activating PP2B in hepatocytes, and PP2B-mediated dephosphorylation of NTCP
      may be involved in cAMP-mediated NTCP translocation to the plasma membrane.

PMID- 12065291
TI  - Metabolic acidosis in rats increases intestinal NHE2 and NHE3 expression and
      function.
AB  - Chronic metabolic acidosis increases intestinal Na absorption, although through
      undefined mechanisms. Whether this occurs through enhanced expression and/or
      function of the brush-border Na+/H+ exchangers (NHE)2 and NHE3 is unknown.
      Metabolic acidosis was induced in rats by feeding ammonium chloride through their
      drinking water. Intestinal NHE activities were measured using brush-border 22Na+
      uptake. Western and Northern blots measured changes in protein and mRNA
      expression, respectively. Acidosis occurred within 2 days of ammonium chloride
      feedings but increased after 6 days. NHE2 and NHE3 activities, protein
      expression, and mRNA levels increased in acidotic rats compared with controls. In
      contrast, basolateral NHE1 expression was not affected. Brush-border alkaline
      phosphatase showed no effect of metabolic acidosis on cellular differentiation.
      This study demonstrated a direct effect of metabolic acidosis on NHE2 and NHE3
      activity, expression, and gene transcription. Metabolic acidosis is one of the
      few circumstances shown to affect NHE2 function and expression, thus providing
      insights into the role of NHE2 on intestinal physiology.

PMID- 12065292
TI  - Diurnal rhythm of H+-peptide cotransporter in rat small intestine.
AB  - In mammals, most physiological, biochemical, and behavioral processes show a
      circadian rhythm. In the present study, we examined the diurnal rhythm of the H+
      peptide cotransporter (PEPT1), which transports small peptides and peptide-like
      drugs in the small intestine and kidney, using rats maintained in a 12-h
      photoperiod with free access to chow. The transport of [14C]glycylsarcosine (Gly
      Sar), a typical substrate for PEPT1 by in situ intestinal loop and everted
      intestine, was greater in the dark phase than the light phase. PEPT1 protein and
      mRNA levels varied significantly, with a maximum at 2000 and minimum at 800.
      Similar functional and expressional diurnal variations were observed in the
      intestinal Na+-glucose cotransporter (SGLT1). In contrast, renal PEPT1 and SGLT1
      showed little diurnal rhythmicity in protein and mRNA expression. These findings
      indicate that the intestinal PEPT1 undergoes diurnal regulation in its activity
      and expression, and this could affect the intestinal absorption of dietary
      protein.

PMID- 12065293
TI  - Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol.
AB  - The mechanism by which alcohol injures the pancreas remains unknown. Recent
      investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative
      metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this
      study, we characterized ethanol-induced injury in rats and evaluated the
      contribution of oxidative and nonoxidative ethanol metabolites in this form of
      acute pancreatitis. Pancreatic injury in rats was assessed by edema,
      intrapancreatic trypsinogen activation, and microscopy after infusing ethanol
      with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue
      levels of FAEE and ethanol were measured and correlated with pancreatic injury.
      Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent
      fashion, induced a pancreas-specific injury consisting of edema, trypsinogen
      activation, and formation of vacuoles in the pancreatic acini. Inhibition of the
      oxidation of ethanol significantly increased both FAEE concentration in plasma
      and pancreas and worsened the pancreatitis-like injury. This study provides
      direct evidence that ethanol, through its nonoxidative metabolic pathway, can
      produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible
      for the development of early pancreatic cell damage in acute alcohol-induced
      pancreatitis.

PMID- 12065294
TI  - Release of ATP during host cell killing by enteropathogenic E. coli and its role
      as a secretory mediator.
AB  - Enteropathogenic Escherichia coli (EPEC) causes severe, watery diarrhea in
      children. We investigated ATP release during EPEC-mediated killing of human cell
      lines and whether released adenine nucleotides function as secretory mediators.
      EPEC triggered a release of ATP from all human cell lines tested: HeLa, COS-7,
      and T84 (colon cells) as measured using a luciferase kit. Accumulation of ATP in
      the supernatant medium was enhanced if an inhibitor of 5'-ectonucleotidase was
      included and was further enhanced if an ATP-regenerating system was added. In the
      presence of the inhibitor/regenerator, ATP concentrations in the supernatant
      medium reached 1.5-2 microM 4 h after infection with wild-type EPEC strains. In
      the absence of the inhibitor/regenerator system, extracellular ATP was rapidly
      broken down to ADP, AMP, and adenosine. Conditioned medium from EPEC-infected
      cells triggered a brisk chloride secretory response in intestinal tissues studied
      in the Ussing chamber (rabbit distal colon and T84 cell monolayers), whereas
      conditioned medium from uninfected cells and sterile filtrates of EPEC bacteria
      did not. The short-circuit current response to EPEC-conditioned medium was
      completely reversed by adenosine receptor blockers, such as 8-(p-sulfophenyl)
      theophylline and MRS1754. EPEC killing of host cells releases ATP, which is
      broken down to adenosine, which in turn stimulates secretion via apical adenosine
      A2b receptors. These findings provide new insight into how EPEC causes watery
      diarrhea.

PMID- 12065295
TI  - Effects of bile acids on the muscle functions of guinea pig gallbladder.
AB  - Hydrophobic bile acids impair gallbladder emptying in vivo and inhibit
      gallbladder muscle contraction in response to CCK-8 in vitro. This study was
      aimed at determining the mechanisms of muscle cell dysfunction caused by bile
      acids in guinea pig gallbladders. Muscle cells were obtained by enzymatic
      digestion. Taurochenodeoxycholic acid (TCDC), a hydrophobic bile acid, caused a
      contraction of up to 15% and blocked CCK-induced contraction. Indomethacin
      abolished the TCDC-induced contraction. Hydrophilic bile acid
      tauroursodeoxycholic acid (TUDC) had no effect on muscle contraction but
      prevented the TCDC-induced contraction and its inhibition on CCK-induced
      contraction. Pretreatment with NADPH oxidase inhibitor PH2I, xanthine oxidase
      inhibitor allopurinol, and free-radical scavenger catalase also prevented TCDC
      induced contraction and its inhibition of the CCK-induced contraction. TCDC
      caused H2O2 production, lipid peroxidation, and increased PGE2 synthesis and
      activities of catalase and SOD. These changes were significantly inhibited by
      pretreatment of PH2I or allopurinol. Inhibitors of cytosolic phospholipase A2
      (cPLA2), protein kinase C (PKC), and mitogen-activating protein kinase (MAPK)
      also blocked the TCDC-induced contraction. It is concluded that hydrophobic bile
      acids cause muscle cell dysfunction by stimulating the formation of H2O2 via
      activation of NADPH and xanthine oxidase. H2O2 causes lipid peroxidation and
      activates cPLA2 to increase PGE2 production, which, in turn, stimulates the
      synthesis of free-radical scavengers through the PKC-MAPK pathway.

PMID- 12065296
TI  - Multimodal assessment of pain in the esophagus: a new experimental model.
AB  - A new multimodal pain assessment model was developed integrating electrical,
      mechanical, cold, and warmth stimuli into the same device. The device, with a bag
      and electrodes for electrical stimulation, was positioned in the lower part of
      the esophagus in 11 healthy subjects. Mechanical stimuli were delivered with an
      impedance planimetric system. Thermal stimuli were performed by circulating water
      of different temperatures (5-50 degrees C) inside the bag. All subjects reported
      both nonpainful and painful local and referred sensations to all stimuli.
      Temporal summation to repeated electrical stimuli could be studied. For all
      stimuli, there was a relationship between stimulus intensity and pain intensity.
      The referred pain area increased with increasing intensity of the electrical and
      mechanical stimuli. There were several differences between the sensations evoked
      by the four stimulus modalities, indicating activation of different visceral
      nerve pathways. This model offers the possibility for controlled multimodal
      stimuli activating the superficial and deeper layers of the human gut and should
      be used in basic, clinical, and pharmacological pain studies.

PMID- 12065297
TI  - Role of Ca2+-activated Cl- channels and MLCK in slow IJP in opossum esophageal
      smooth muscle.
AB  - The possible contribution of Ca2+-activated Cl- channel [I(Cl(Ca))] and myosin
      light-chain kinase (MLCK) to nonadrenergic, noncholinergic slow inhibitory
      junction potentials (sIJP) was studied using conventional intracellular
      microelectrode recordings in circular smooth muscle of opossum esophageal body
      and guinea pig ileum perfused with Krebs solution containing atropine (3 microM),
      guanethidine (3 microM), and substance P (1 microM). In opossum esophageal
      circular smooth muscle, resting membrane potential (MP) was -51.9 +/- 0.7 mV (n =
      89) with MP fluctuations of 1-3 mV. A single square-wave nerve stimulation of 0.5
      ms duration and 80 V induced a sIJP with amplitude of 6.3 +/- 0.2 mV, half
      amplitude duration of 635 +/- 19 ms, and rebound depolarization amplitude of 2.4
      +/- 0.1 mV (n = 89). 9-Anthroic acid (A-9-C), niflumic acid (NFA), wortmannin,
      and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9)
      abolished MP fluctuations, sIJP, and rebound depolarization in a concentration
      dependent manner. A-9-C and NFA but not wortmannin and ML-9 hyperpolarized MP. In
      guinea pig ileal circular smooth muscle, nerve stimulation elicited an IJP
      composed of both fast (fIJP) and slow (sIJP) components, followed by rebound
      depolarization. NFA (200 microM) abolished sIJP and rebound depolarization but
      left the fIJP intact. These data suggest that in the tissues studied, activation
      of I(Cl(Ca)), which requires MLCK, contributes to resting MP, and that closing of
      I(Cl(Ca)) is responsible for sIJP.

PMID- 12065298
TI  - IL-4 inhibits vasoactive intestinal peptide production by macrophages.
AB  - In schistosomiasis, eggs induce granulomas that have a vasoactive intestinal
      peptide (VIP) immunoregulatory circuit. This study explored the regulation of VIP
      production at sites of inflammation. Splenocytes from uninfected C57BL/6 mice
      expressed VIP mRNA and protein, which stopped following egg deposition. Eggs
      induce a Th2 response, suggesting that Th2 cytokines like interleukin (IL)-4 can
      regulate VIP. To address this issue, splenocytes from uninfected mice were
      incubated for 4 h with or without recombinant IL-4. IL-4 inhibited VIP mRNA
      expression. F4/80+ macrophages were the source of constitutively expressed VIP,
      subject to IL-4 regulation. In IL-4 knockout mice, splenic VIP production did not
      downmodulate during schistosome infection, suggesting that IL-4 is a critical
      cytokine regulating VIP production in wild-type mouse spleen. IL-4-producing
      granulomas in schistosomiasis made VIP. Experiments showed that granuloma VIP
      derived from F4/80- (nonmacrophage) cell populations, explaining this paradox.
      Granuloma F4/80+ cells from IL-4 knockout mice expressed VIP. Thus macrophages
      can make VIP, which is subject to IL-4 regulation. However, in the Th2
      granulomas, other cell types produce VIP, which compensates for loss of
      macrophages as a source of this molecule.

PMID- 12065299
TI  - Na+/H+ exchanger blockade inhibits enterocyte inflammatory response and protects
      against colitis.
AB  - Na+/H+ exchangers (NHEs) are integral transmembrane proteins found in all
      mammalian cells. There is substantial evidence indicating that NHEs regulate
      inflammatory processes. Because intestinal epithelial cells express a variety of
      NHEs, we tested the possibility that NHEs are also involved in regulation of the
      epithelial cell inflammatory response. In addition, since the epithelial
      inflammatory response is an important contributor to mucosal inflammation in
      inflammatory bowel disease (IBD), we examined the role of NHEs in the modulation
      of disease activity in a mouse model of IBD. In human gut epithelial cells, NHE
      inhibition using a variety of agents, including amiloride, 5-(N-methyl-N
      isobutyl)amiloride, 5-(N-ethyl-N-isopropyl)- amiloride, harmaline, clonidine, and
      cimetidine, suppressed interleukin-8 (IL-8) production. The inhibitory effect of
      NHE inhibition on IL-8 was associated with a decrease in IL-8 mRNA accumulation.
      NHE inhibition suppressed both activation of the p42/p44 mitogen-activated
      protein kinase and nuclear factor-kappaB. Finally, NHE inhibition ameliorated the
      course of IBD in dextran sulfate-treated mice. Our data demonstrate that
      inhibition of NHEs may be an approach worthy of pursuing for the treatment of
      IBD.

PMID- 12065300
TI  - Regulation of oligopeptide transporter (Pept-1) in experimental diabetes.
AB  - The knowledge of expression and biology of the intestinal oligopeptide
      transporter (Pept-1) in a metabolic disorder such as diabetes may have
      nutritional and pharmacological implications. To study this problem, rats were
      made diabetic by streptozotocin injection, and Western and Northern blot analyses
      and nuclear run-on assay were used to determine the protein and gene expressions
      of Pept-1 and its rate of transcription, respectively. Uncontrolled diabetes for
      96 h increased the activity of Pept-1 in the brush-border membrane of intestinal
      mucosa. Studies of Michaelis-Menten constant, maximal velocity, and protein
      expression of Pept-1 indicated that an increase in the abundance of this
      transporter was responsible for the increased activity. Studies of the gene
      expression showed that uncontrolled diabetes increased the abundance of mRNA
      encoding Pept-1 without altering its rate of transcription. Lastly, studies of
      the specificity of the above effect showed that uncontrolled diabetes similarly
      affected the protein and gene expressions of Pept-1 located in the kidney. In
      conclusion, the data show that 1) uncontrolled diabetes has a tropic effect on
      Pept-1 and 2) the effect is systemic, and its molecular mechanism appears to be
      an increase in the stabilization of mRNA encoding Pept-1.

PMID- 12065301
TI  - Molecular mechanisms of leukocyte recruitment in postischemic liver
      microcirculation.
AB  - Evidence shows that leukocyte recruitment into inflamed liver sinusoids does not
      require selectins, with one notable exception: ischemia-reperfusion (I/R). We
      used intravital microscopy to directly visualize the liver microcirculation
      during I/R and localized endotoxemia (liver superfused with lipopolysaccharide).
      General anti-selectin therapy (fucoidan) or anti-adhesion therapy with an
      antithrombin inhibitor (hirudin) was also used. Many neutrophils rolled and
      adhered in postsinusoidal vessels and sequestered in the sinusoids during I/R and
      local endotoxin superfusion. Although fucoidan blocked rolling in both forms of
      inflammation, leukocyte recruitment into sinusoids was only blocked in I/R.
      Adhesion was also inhibited in postischemic sinusoids with a second anti-adhesive
      agent (hirudin). Because liver I/R inevitably induces ischemia upstream in the
      intestine, anti-selectin therapy may prevent intestinal injury, which could
      prevent downstream liver inflammation. To test this hypothesis, we completely
      removed the intestine and rerouted blood flow from the superior mesenteric artery
      to the superior mesenteric vein. I/R was induced in the liver microcirculation,
      and many leukocytes rolled and adhered in postsinusoidal venules and adhered in
      sinusoids. Although fucoidan significantly reduced the rolling in postsinusoidal
      vessels, adhesion persisted in the sinusoids. Our data suggest that anti-adhesion
      therapy is effective in liver I/R in the sinusoids and postsinusoidal venules,
      perhaps in part due to its beneficial effect on the intestine.

PMID- 12065302
TI  - Integrative control of rectoanal reflex in guinea pigs through lumbar colonic
      nerves.
AB  - The aim of the present study was to analyze the neuromodulation of rectoanal
      reflex activity by lumbar sympathetic nerves in guinea pigs. The mechanical
      activities of the rectum were recorded with a balloon connected to a pressure
      transducer, and those of the internal anal sphincter (IAS) were recorded with a
      custom-made strain gauge force transducer. Gradual and sustained rectal
      distension evoked the rectoanal reflex, causing cholinergic contractions of the
      rectum and synchronous nitrergic relaxations of the IAS. Section of the lumbar
      colonic nerves enhanced both rectal contractions and IAS relaxations. Section of
      the 13th thoracic cord abolished both rectal contractions and IAS relaxations,
      but section of the lumbar colonic nerves restored them. Lumbar sympathectomy and
      pithing sacral cords greatly diminished these rectal contractions and IAS
      relaxations, but the intrinsic reflex component remained. NG-nitro-L-arginine
      methyl ester enhanced the intrinsic reflex-mediated contraction of the rectum and
      abolished reflex-mediated relaxation of the IAS and converted into cholinergic
      contractions. The present results indicate that the extrinsic lumbar inhibitory
      outflow causes marked inhibition of the rectoanal reflex via the lumbar colonic
      nerves.

PMID- 12065303
TI  - Inducible nitric oxide synthase mediates early epithelial repair of porcine
      ileum.
AB  - Reports conflict regarding the effect of nitric oxide (NO) on intestinal
      epithelium. In chronic injury, NO appears detrimental by combining with reactive
      oxygen to form potent-free radicals. In contrast, inhibition of NO synthesis
      after acute injury exacerbates damage and inflammation. Recent studies have
      disclosed constitutive expression of inducible NO synthase (iNOS) by normal
      intestinal epithelia, yet little attention has been given to the role of iNOS in
      acute epithelial repair. We studied the local effects of iNOS on early epithelial
      repair of porcine ileal mucosa injured by deoxycholate within Ussing chambers.
      iNOS was constitutively expressed by the villous epithelium, and after
      deoxycholate injury, iNOS was expressed by injured and detaching enterocytes.
      Selective inhibition of iNOS abolished increases in NO synthesis and villous
      reepithelialization after injury. Exogenous L-arginine rescued baseline
      reepithelialization from NOS inhibitors but was only capable of stimulating
      additional repair in the presence of serum. These results demonstrate that iNOS
      derived NO is a key mediator of early villous reepithelialization following acute
      mucosal injury.

PMID- 12065304
TI  - Distinct epithelial responses in experimental colitis: implications for ion
      uptake and mucosal protection.
AB  - In the present study, we aimed to investigate enterocyte- and goblet cell
      specific functions during the different phases of acute colitis induced with
      dextran sulfate sodium (DSS). Rats were treated with DSS for 7 days, followed by
      a 7-day recovery period. Colonic tissue was excised on days 2 (onset of disease),
      7 (active disease), and 14 (regenerative phase). Enterocyte functions were
      studied by the expression of carbonic anhydrases (CAs), sodium/hydrogen
      exchangers (NHEs) and intestinal fatty acid-binding protein (iFABP) and by
      alkaline phosphatase (AP) activity. The expression and secretion of the mucin
      Muc2 and trefoil factor family peptide-3 (TFF3) were used as parameters for
      goblet cell function. DSS induced a downregulation of the CAs, NHEs, and iFABP in
      some normal-appearing surface enterocytes and in most of the flattened-surface
      enterocytes during disease onset and active disease. During the regenerative
      phase most enterocytes expressed these genes again. Quantitative analysis
      revealed a significant decrease in CAs, NHEs, and iFABP expression levels during
      onset and active disease. During the regenerative phase, the expression levels of
      the CAs were restored, whereas the expression levels of the NHEs and iFABP
      remained decreased. In contrast, enterocyte-specific AP activity was maintained
      in normal and flattened enterocytes during DSS-induced colitis. Goblet cells
      continued to express MUC2 and TFF3 during and after DSS treatment. Moreover, Muc2
      and TFF3 expression and secretion levels were maintained or even increased during
      each of the DSS-induced disease phases. In conclusion, DSS-induced colitis was
      associated with decreased expression of CAs, NHEs, and iFABP. The loss of these
      genes possibly accounts for some of the pathology seen in colitis. The
      maintenance or upregulation of Muc2 and TFF3 synthesis and secretion levels
      implies that goblet cells at least maintain their epithelial defense and repair
      capacity during acute inflammation induced by DSS.

PMID- 12065305
TI  - Kininogen deficiency modulates chronic intestinal inflammation in genetically
      susceptible rats.
AB  - Genetically susceptible Lewis rats injected in the intestinal wall with
      peptidoglycan-polysaccharide (PG-APS) polymers develop chronic granulomatous
      enterocolitis concomitant with activation of the kallikrein-kinin system. To
      elucidate the role of high-molecular-weight kininogen (HK) in chronic
      enterocolitis, we back crossed Brown-Norway rats having a HK deficiency with
      Lewis rats for five generations. Two new strains were produced, wild-type F5
      (F5WT) and HK deficient (F5HKd), each with a approximately 97% Lewis genome. The
      HK values of F5WT and F5HKd rat plasma were 0.62 +/- 0.20 and 0.08 +/- 0.03 U/ml,
      respectively. In PG-APS-injected rats, chronic inflammation was measured by using
      gross gut score, histological inflammation, liver granuloma, and white blood cell
      count. The mean gross gut scores were significantly lower in the F5HKd than in
      the F5WT rats. Plasma T-kininogen was significantly less in F5HKd. These results
      indicate the importance of the kallikrein-kinin system in this model of chronic
      enterocolitis and systemic inflammation.

PMID- 12065306
TI  - Lactoferrin reduces colitis in rats via modulation of the immune system and
      correction of cytokine imbalance.
AB  - Natural immunomodulator lactoferrin is known to exert an anti-inflammatory
      effect. However, there have been no studies that examine the mode of action of
      lactoferrin in reducing intestinal damage. We investigated the effect of
      lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in
      rats. Bovine lactoferrin was given once daily through gavage, starting 3 days
      before (preventive mode) or just after TNBS administration (treatment mode) until
      death. The distal colon was removed to be examined. Colitis was attenuated by
      lactoferrin via both modes in a dose-dependent manner, as reflected by
      improvement in macroscopic and histological scores and myeloperoxidase activity.
      Lactoferrin caused significant induction of the anti-inflammatory cytokines
      interleukin (IL)-4 and IL-10, significant reductions in the proinflammatory
      cytokines tumor necrosis factor-alpha and IL-1beta, and downregulation of the
      nuclear factor-kappaB pathway. We concluded that lactoferrin exerts a protective
      effect against colitis in rats via modulation of the immune system and correction
      of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for
      inflammatory bowel disease.

PMID- 12065307
TI  - Role of ICAM-1 in chronic hepatic allograft rejection in the rat.
AB  - The pathogenesis of hepatic allograft rejection remains unclear. We aimed to
      clarify the early role of intercellular adhesion molecule-1 (ICAM-1)-mediated
      cell recruitment in chronic hepatic rejection. Liver transplantation was
      performed from Lewis to Lewis rats (isograft controls) and from Lewis to Brown
      Norway rats (allograft rejection group). The allografted rats were treated with
      either ICAM-1 antisense oligonucleotides (10 mg. kg(-1). day(-1) x 6 days ip) or
      a control preparation (either ICAM-1 missense oligonucleotide or normal saline).
      Hepatic leukocyte recruitment in vivo was studied on day 6 by using intravital
      microscopy. Liver histology, biochemistry, and survival rates were also examined.
      Leukocyte adhesion in terminal hepatic venules was significantly increased in the
      rejection group compared with isograft controls. Antisense ICAM-1 in the
      allografted group effectively reduced leukocyte adhesion. Histology and liver
      chemistry were less deranged in the antisense-treated groups compared with
      control-treated allografted rats. In the allograft groups, survival was
      significantly prolonged in the antisense-treated rats (42.3 +/- 1.2 days)
      compared with the controls (25.2 +/- 2.7 days). These results showed that early
      leukocyte recruitment in the hepatic microvasculature of rejecting allografts is
      ICAM-1 dependent and suggest that impacting on early cell recruitment can
      significantly ameliorate chronic rejection.

PMID- 12065308
TI  - Role of glycogen synthase kinase-3 in TNF-alpha-induced NF-kappaB activation and
      apoptosis in hepatocytes.
AB  - Nuclear factor-kappaB (NF-kappaB) prevents hepatocytes from undergoing apoptosis
      during development and liver regeneration. Mice with inactivated glycogen
      synthase kinase (GSK)-3beta die from hepatocyte apoptosis during development due
      to a defect in NF-kappaB activation (Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin
      O, and Woodgett JR. Nature 406: 86-90, 2000). In this study, we determined the
      role of GSK-3 in TNF-alpha-induced NF-kappaB activation and cell death in primary
      hepatocytes. LiCl, an established inhibitor of GSK-3, sensitized primary rat
      hepatocytes toward TNF-alpha-mediated apoptosis resulting in 90% cell death after
      24 h. This was accompanied by increased caspase 8-like and 3-like activities,
      nuclear fragmentation and DNA laddering. LiCl treatment had no effect on IkappaB
      alpha degradation, IkappaB kinase (IKK) activity, NF-kappaB binding activity, and
      p65 nuclear import and export, but decreased transcription of the NF-kappaB
      dependent inducible nitric oxide synthase gene and a NF-kappaB-driven reporter
      gene. The p65 sequence revealed four potential GSK-3 phosphorylation sites within
      its COOH-terminal transactivation domains and recombinant GSK-3beta
      phosphorylated glutathione S-transferase (GST)-p65(354-551), but not GST-p65(1
      305) in vitro. These results indicate that GSK-3 protects hepatocytes from TNF
      alpha-induced apoptosis through p65 phosphorylation and upregulation of NF-kappaB
      transactivation.

PMID- 12065309
TI  - Ethyl pyruvate modulates inflammatory gene expression in mice subjected to
      hemorrhagic shock.
AB  - Administration of pyruvate, an effective scavenger of reactive oxygen species,
      has been shown to be salutary in numerous models of redox-mediated tissue or
      organ injury. Pyruvate, however, is unstable in solution and, hence, is not
      attractive for development as a therapeutic agent. Herein, ethyl pyruvate, which
      is thought to be more stable than the parent compound, was formulated in a
      calcium-containing balanced salt solution [Ringer ethyl pyruvate solution (REPS)]
      and evaluated in a murine model of hemorrhagic shock and resuscitation (HS/R).
      Resuscitation with REPS instead of Ringer lactate solution (RLS) significantly
      improved survival at 24 h and abrogated bacterial translocation to mesenteric
      lymph nodes and the development of increased ileal mucosal permeability to FITC
      labeled dextran (4,000 Da) at 4 h. Mice treated with REPS instead of RLS also had
      lower circulating levels of alanine aminotransferase at 4 h. Treatment with REPS
      instead of RLS decreased activation of nuclear factor-kappaB in liver and colonic
      mucosa after HS/R and also decreased the expression of inducible nitric oxide
      synthase, tumor necrosis factor, cyclooxygenase-2, and interleukin-6 mRNA in
      liver, ileal mucosa, and/or colonic mucosa. These data support the view that
      resuscitation with REPS modulates the inflammatory response and decreases
      hepatocellular and gut mucosal injury in mice subjected to HS/R.

PMID- 12065310
TI  - H+-peptide cotransport in the human bile duct epithelium cell line SK-ChA-1.
AB  - This study describes for the first time the presence of H+-peptide cotransport in
      cells of the bile duct. Uptake of [glycine-1-14C]glycylsarcosine ([14C]Gly-Sar)
      in human extrahepatic cholangiocarcinoma SK-ChA-1 cells was stimulated sevenfold
      by an inwardly directed H+ gradient. Transport was mediated by a low-affinity
      system with a transport constant (Kt) value of 1.1 mM. Several dipeptides,
      cefadroxil, and delta-aminolevulinic acid, but not glycine and glutathione, were
      strong inhibitors of Gly-Sar uptake. SK-ChA-1 cells formed tight, polarized
      monolayers on permeable membranes. The transepithelial electrical resistance was
      856 +/- 29 omega x cm(2). The transepithelial flux of [14C]Gly-Sar in apical-to
      basolateral direction exceeded the basolateral-to-apical flux 11-fold. Uptake was
      20-fold higher from the apical side. RT-PCR analysis using primer pairs specific
      for the intestinal-type peptide transporter (PEPT1) or kidney-type (PEPT2)
      revealed that the transport system expressed in SK-ChA-1 and also in cells of the
      native rabbit bile duct is PEPT1. Immunohistochemistry localized PEPT1 to the
      apical membrane of cholangiocytes of mouse extrahepatic biliary duct. We conclude
      that the cells of the mammalian extrahepatic biliary tract epithelium express the
      intestinal-type H+-peptide cotransporter in their apical membrane. SK-ChA-1 cells
      represent a convenient model to study the physiological and clinical aspects of
      peptide transport in cholangiocytes.

PMID- 12065311
TI  - Role of extrinsic innervation in modulating nitrergic transmission in the canine
      ileocolonic region.
AB  - The human colon can dilate, often to life-threatening proportions. Our aim was to
      explore nitrergic mechanisms underlying colonic dilation in conscious dogs with
      enterically isolated ileocolonic loops either extrinsically innervated (n = 4) or
      extrinsically denervated (n = 4). We recorded phasic pressures in ileum and
      ileocolonic sphincter (ICS), colonic tone, compliance, and relaxation during
      ileal distension. By NADPH-diaphorase histochemistry, we assessed effects of
      extrinsic denervation and enteric isolation on nitrergic fibers. Extrinsic
      denervation increased phasic pressures in ileum, ICS, and colon and abolished ICS
      and colonic relaxation in response to ileal distension. The nitric oxide synthase
      (NOS) inhibitor N(omega)-nitro-L-arginine (L-NNA) increased phasic pressures at
      all sites and ICS tone but did not abolish colonic relaxation during ileal
      distension in innervated loops. L-NNA reduced compliance and induced colonic high
      amplitude propagated contractions in denervated loops. The NOS substrate donor L
      arginine reversed effects of L-NNA. The number of NADPH-diaphorase fibers
      increased in both enterically isolated preparations. Nonnitrergic extrinsic nerve
      pathways mediate reflex colonic relaxation during ileal distension. Enteric
      isolation augments the number of NOS fibers, an effect not modified by extrinsic
      denervation.

PMID- 12065312
TI  - Expression of calcium-sensing receptor in rat colonic epithelium: evidence for
      modulation of fluid secretion.
AB  - The calcium-sensing receptor (CaSR) is activated by extracellular calcium
      (Ca2+(o)) and mediates many of the known effects of extracellular divalent
      minerals on body cells. Both surface and crypt cells express CaSR transcripts and
      protein on both apical and basolateral surfaces. Raising Ca2+(o) elicited
      increases in intracellular calcium (Ca2+(o)) in both surface and crypt cells with
      an EC50 of 2 mM. The Ca-induced increase in Ca2+(i) was associated with increases
      in inositol 1,4,5-trisphosphate and eliminated by U-73129, an inhibitor of
      phosphatidylinositol-phospholipase C, as well as by thapsigargin. Other CaSR
      agonists, Gd3+ and neomycin, mimicked these Ca2+(o)-induced responses. Both
      luminal and bath Ca2+(o), Gd3+, and neomycin induced increases in Ca2+(i) in
      isolated perfused crypts. The stimulatory effect of forskolin on net fluid
      secretion in perfused crypts was abolished by increasing Ca2+(o) in either
      luminal or bath perfusates. Thus both apical and basolateral CaSR on crypt cells
      are functional and provide pathways modulating net intestinal fluid transport
      that may have important implications for the prevention and treatment of certain
      diarrheal diseases associated with elevated cAMP.

PMID- 12065313
TI  - Leukocyte-induced microvascular permeability: how contractile tweaks lead to
      leaks.

PMID- 12065314
TI  - Platelets in atherosclerosis: a new role for beta-amyloid peptide beyond
      Alzheimer's disease.

PMID- 12065315
TI  - Tyrosine kinase activity of discoidin domain receptor 1 is necessary for smooth
      muscle cell migration and matrix metalloproteinase expression.
AB  - Smooth muscle cell (SMC) interactions with collagen mediate cell migration during
      the pathogenesis of atherosclerosis and restenosis. Discoidin domain receptors
      (DDRs) have been identified as novel collagen receptors. We used aortic SMCs from
      wild-type and DDR1(-/-) mice to evaluate the function of the DDR1 in regulating
      migration. DDR1(-/-) SMCs exhibited impaired attachment to and migration toward a
      type I collagen substrate. Matrix metalloproteinase-2 (MMP-2) and MMP-9
      activities were concomitantly reduced in these cells. Transfection of a full
      length cDNA for DDR1b rescued these deficits, whereas kinase-dead mutants of DDR1
      restored attachment but not migration and MMP production. These results suggest
      that active DDR1 kinase is a central mediator of SMC migration.

PMID- 12065316
TI  - Small amounts of alpha-myosin heavy chain isoform expression significantly
      increase power output of rat cardiac myocyte fragments.
AB  - Myocardial performance is likely affected by the relative expression of the two
      myosin heavy chain (MyHC) isoforms, namely alpha-MyHC and beta-MyHC. The relative
      expression of each isoform is regulated developmentally and in pathophysiological
      states. Many pathophysiological states are associated with small shifts in the
      relative expression of each MyHC isoform, yet the functional consequence of these
      shifts remains unclear. The purpose of this study was to determine the functional
      effect of a small shift in the relative expression of alpha-MyHC. To this end,
      power output was measured in rat cardiac myocyte fragments that expressed
      approximately 12% alpha-MyHC and in myocyte fragments that expressed
      approximately 0% alpha-MyHC, as determined in the same cells by SDS-PAGE analysis
      after mechanical experiments. Myocyte fragments expressing approximately 12%
      alpha-MyHC developed approximately 52% greater peak normalized power output than
      myocyte fragments expressing approximately 0% alpha-MyHC. These results indicate
      that small amounts of alpha-MyHC expression significantly augment myocyte power
      output.

PMID- 12065317
TI  - Glu298Asp endothelial nitric oxide synthase gene polymorphism interacts with
      environmental and dietary factors to influence endothelial function.
AB  - An endothelial nitric oxide synthase (eNOS) gene polymorphism (Glu298Asp) has
      been associated with cardiovascular disease. We investigated whether carriage of
      the polymorphism was associated with functional changes in the endothelium, and
      how genotype altered the harmful and beneficial impact of environmental
      influences on the endothelium. Endothelium-dependent, flow-mediated brachial
      artery dilatation (FMD) and endothelium-independent dilatation response to
      glyceryl trinitrate were measured using high-resolution ultrasound in 248
      subjects (131 female, 117 male, aged 20 to 28) genotyped for the Glu298Asp
      polymorphism. Vascular function was compared between genotype groups and
      interactions with the proatherogenic risk factor, smoking, and the
      antiatherogenic influence of n-3 fatty acids (n-3FA) were investigated. Vascular
      function was not related to genotype in the group as a whole or within sexes.
      However, among males, smoking was associated with lower FMD in Asp298 carriers
      (nonsmokers 0.125+/-0.085 mm versus smokers 0.070+/-0.060 mm, P=0.006) but not in
      Glu298 homozygotes (nonsmokers 0.103+/-0.090 mm versus smokers 0.124+/-0.106,
      P=0.5). In the whole group, n-3FA levels were positively related to FMD in Asp298
      carriers (reg coeff=0.023 mm/%, P=0.04, r=0.20) but not in Glu298 homozygotes
      (reg coeff=-0.019 mm/%, P=0.1). These differences between genotype groups were
      significant in interaction models. The Glu298Asp polymorphism is associated with
      differences in endothelial responses to both smoking and n-3 FA in healthy young
      subjects. These findings raise the possibility of genotype-specific prevention
      strategies in cardiovascular disease.

PMID- 12065319
TI  - Importance of monocyte chemoattractant protein-1 pathway in neointimal
      hyperplasia after periarterial injury in mice and monkeys.
AB  - Neointimal hyperplasia is a major cause of restenosis after coronary
      intervention. Because vascular injury is now recognized to involve an
      inflammatory response, monocyte chemoattractant protein-1 (MCP-1) might be
      involved in underlying mechanisms of restenosis. In the present study, we
      demonstrate the important role of MCP-1 in neointimal hyperplasia after cuff
      induced arterial injury. In the first set of experiments, placement of a
      nonconstricting cuff around the femoral artery of intact mice and monkeys
      resulted in inflammation in the early stages and subsequent neointimal
      hyperplasia at the late stages. We transfected with an N-terminal deletion mutant
      of the human MCP-1 gene into skeletal muscles to block MCP-1 activity in vivo.
      This mutant MCP-1 works as a dominant-negative inhibitor of MCP-1. This strategy
      inhibited early vascular inflammation (monocyte infiltration, increased
      expression of MCP-1, and inflammatory cytokines) and late neointimal hyperplasia.
      In the second set of experiments, the cuff-induced neointimal hyperplasia was
      found to be less in CCR2-deficient mice than in control CCR2(+/+) mice. The MCP
      1/CCR2 pathway plays a central role in the pathogenesis of neointimal hyperplasia
      in cuffed femoral artery of mice and monkeys. Therefore, the MCP-1/CCR2 pathway
      can be a therapeutic target for human restenosis after coronary intervention.

PMID- 12065318
TI  - Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar
      function.
AB  - We aimed to elucidate the possible role of phenotypic alterations and oxidative
      stress in age-related endothelial dysfunction of coronary arterioles. Arterioles
      were isolated from the hearts of young adult (Y, 14 weeks) and aged (A, 80 weeks)
      male Sprague-Dawley rats. For videomicroscopy, pressure-induced tone of Y and A
      arterioles and their passive diameter did not differ significantly. In A,
      arterioles L-NAME (a NO synthase blocker)-sensitive flow-induced dilations were
      significantly impaired (Y: 41+/-8% versus A: 3+/-2%), which could be augmented by
      superoxide dismutase (SOD) or Tiron (but not L-arginine or the TXA(2) receptor
      antagonist SQ29,548). For lucigenin chemiluminescence, O(2)(.-) generation was
      significantly greater in A than Y vessels and could be inhibited with SOD and
      diphenyliodonium. NADH-driven O(2)(.-) generation was also greater in A vessels.
      Both endothelial and smooth muscle cells of A vessels produced O(2)(.-) (shown
      with ethidium bromide fluorescence). For Western blotting, expression of eNOS and
      COX-1 was decreased in A compared with Y arterioles, whereas expressions of COX
      2, Cu/Zn-SOD, Mn-SOD, xanthine oxidase, and the NAD(P)H oxidase subunits
      p47(phox), p67(phox), Mox-1, and p22(phox) did not differ. Aged arterioles showed
      an increased expression of iNOS, confined to the endothelium. Decreased eNOS mRNA
      and increased iNOS mRNA expression in A vessels was shown by quantitative RT-PCR.
      In vivo formation of peroxynitrite was evidenced by Western blotting, and
      immunohistochemistry showing increased 3-nitrotyrosine content in A vessels.
      Thus, aging induces changes in the phenotype of coronary arterioles that could
      contribute to the development of oxidative stress, which impairs NO-mediated
      dilations.

PMID- 12065320
TI  - Frequency-dependent breakdown of wave propagation into fibrillatory conduction
      across the pectinate muscle network in the isolated sheep right atrium.
AB  - Atrial fibrillation (AF) may result from stationary reentry in the left atrium
      (LA), with fibrillatory conduction toward the right atrium (RA). We hypothesize
      that periodic input to the RA at an exceedingly high frequency results in
      disorganized wave propagation, compatible with fibrillatory conduction.
      Simultaneous endocardial and epicardial optical mapping (di-4-ANEPPS) was
      performed in isolated, coronary-perfused sheep RA. Rhythmic pacing of Bachmann's
      bundle allowed well-controlled and realistic conditions for LA-driven RA. Pacing
      at increasingly higher frequencies (2.0 to 6.0 Hz) led to increasing delays in
      activation distal to major branching sites of the crista terminalis and pectinate
      bundles, culminating in spatially distributed intermittent blockade at or above
      approximately 6.5 Hz. At this "breakdown frequency," the direction of RA
      propagation became completely variable from beat to beat and thus transformed
      into fibrillatory conduction. Such frequency-dependent changes were independent
      of action potential duration. Rather, the spatial boundaries between proximal and
      distal frequencies correlated well with branch sites of the pectinate
      musculature. Thus, there exists a breakdown frequency in the sheep RA below which
      activity is periodic throughout the atrium and above which it is fibrillation
      like. The data are consistent with the ideas that during AF, high-frequency
      activation initiated in the LA undergoes fibrillatory conduction toward the RA,
      and that sink-to-source effect at branch points of the crista terminalis and
      pectinate muscles is important in determining the complexity of the arrhythmia.

PMID- 12065321
TI  - Protein kinase A phosphorylates titin's cardiac-specific N2B domain and reduces
      passive tension in rat cardiac myocytes.
AB  - beta-Adrenergic stimulation of cardiac muscle activates protein kinase A (PKA),
      which is known to phosphorylate proteins on the thin and thick filaments of the
      sarcomere. Cardiac muscle sarcomeres contain a third filament system composed of
      titin, and here we demonstrate that titin is also phosphorylated by the beta
      adrenergic pathway. Titin phosphorylation was observed after beta-receptor
      stimulation of intact cardiac myocytes and incubation of skinned cardiac myocytes
      with PKA. Mechanical experiments with isolated myocytes revealed that PKA
      significantly reduces passive tension. In vitro phosphorylation of recombinant
      titin fragments and immunoelectron microscopy suggest that PKA targets a
      subdomain of the elastic segment of titin, referred to as the N2B spring element.
      The N2B spring element is expressed only in cardiac titins, in which it plays an
      important role in determining the level of passive tension. Because titin-based
      passive tension is a determinant of diastolic function, these results suggest
      that titin phosphorylation may modulate cardiac function in vivo.

PMID- 12065322
TI  - Mature vascular endothelium can give rise to smooth muscle cells via endothelial
      mesenchymal transdifferentiation: in vitro analysis.
AB  - Though in the past believed to be a rare phenomenon, endothelial-mesenchymal
      transdifferentiation has been described with increasing frequency in recent
      years. It is believed to be important in embryonic vascular development, yet less
      is known regarding its role in the adult vasculature. Using FACS and
      immunomagnetic (Dynabeads) purification techniques (based on uptake of DiI
      acetylated low-density lipoproteins and/or PECAM-1 expression) and double-label
      indirect immunostaining (for endothelial and smooth muscle [SM] markers), we
      demonstrate that mature bovine vascular endothelium contains cells of an
      endothelial phenotype (defined by VE-cadherin, von Willebrand factor, PECAM-1,
      and elevated uptake of acetylated low-density lipoproteins) that can undergo
      endothelial-mesenchymal transdifferentiation and further differentiate into SM
      cells (as defined by expression of alpha-SM-actin, SM22alpha, calponin, and SM
      myosin). "Transitional" cells, coexpressing both endothelial markers and alpha-SM
      actin, were consistently observed. The percentage of cells capable of endothelial
      mesenchymal transdifferentiation within primary endothelial cultures was
      estimated as 0.01% to 0.03%. Acquisition of a SM phenotype occurred even in the
      absence of proliferation, in gamma-irradiated (30 Gy) and/or mitomycin C-treated
      primary cell cultures. Initiation of transdifferentiation correlated with
      disruption of cell-cell contacts (marked by loss of VE-cadherin expression)
      within endothelial monolayers, as well as with the action of transforming growth
      factor-beta(1). In conclusion, our in vitro data show that mature bovine systemic
      and pulmonary endothelium contains cells that can acquire a SM phenotype via a
      transdifferentiation process that is transforming growth factor-beta(1)- and cell
      cell contact-dependent, but proliferation-independent.

PMID- 12065323
TI  - Platelet phagocytosis and processing of beta-amyloid precursor protein as a
      mechanism of macrophage activation in atherosclerosis.
AB  - In human occluded saphenous vein grafts, we previously demonstrated cytotoxic
      foam cells, presumably derived from macrophages engulfing platelets. In the
      present study, we investigated whether platelet phagocytosis occurs in human
      atherosclerotic plaques, whether this activates macrophages, and whether the
      platelet constituent, amyloid precursor protein (APP), was involved.
      Immunohistochemistry documented the presence of APP, beta-amyloid peptide (Abeta,
      cleaved from APP), and platelets (CD9), along with inducible NO synthase (iNOS)
      and cyclooxygenase-2, two markers of macrophage activation, around microvessels
      in advanced human carotid artery plaques (n=18). Abeta colocalized with iNOS
      expressing macrophages that were often surrounded by platelets. In vitro, murine
      J774 and human THP-1 macrophages were incubated with or without washed human
      platelets. Coincubation of macrophages and platelets led to platelet phagocytosis
      (electron and confocal microscopy) and formation of lipid-, APP-, and Abeta
      containing foam cells. These expressed iNOS mRNA (reverse transcription
      polymerase chain reaction) and protein and produced nitrite and tumor necrosis
      factor-alpha (ELISA). Macrophage pretreatment with 4-(2
      aminoethyl)benzenesulfonyl fluoride, a protease inhibitor, reduced APP processing
      and inhibited NO biosynthesis induced by platelet phagocytosis but not by
      lipopolysaccharides. Human atherosclerotic plaques and J774 and THP-1 macrophages
      contained mRNA of the APP-cleaving enzyme beta-secretase. This is the first
      demonstration of Abeta, a peptide extensively studied in Alzheimer's disease, in
      human atherosclerotic plaques. It was present in activated iNOS-expressing
      perivascular macrophages that had phagocytized platelets. In vitro studies
      indicate that platelet phagocytosis leads to macrophage activation and suggest
      that platelet-derived APP is proteolytically processed to Abeta, resulting in
      iNOS induction. This represents a novel mechanism for macrophage activation in
      atherosclerosis.

PMID- 12065324
TI  - Expression of a functionally active gp91phox-containing neutrophil-type NAD(P)H
      oxidase in smooth muscle cells from human resistance arteries: regulation by
      angiotensin II.
AB  - A major source of vascular smooth muscle cell (VSMC) superoxide is NAD(P)H
      oxidase. However, the molecular characteristics and regulation of this enzyme are
      unclear. We investigated whether VSMCs from human resistance arteries (HVSMCs)
      possess a functionally active, angiotensin II (Ang II)-regulated NAD(P)H oxidase
      that contains neutrophil oxidase subunits, including p22phox, gp91phox, p40phox,
      p47phox, and p67phox. mRNA expression of gp91phox homologues, nox1 and nox4, was
      also assessed in HVSMCs, human aortic smooth muscle cells, and rat VSMCs. HVSMCs
      were obtained from resistance arteries from gluteal biopsies of healthy subjects.
      gp91phox and nox4, but not nox1, were detected in HVSMCs. Nox1 and nox4, but not
      gp91phox, were expressed in human aortic smooth muscle cells and rat VSMCs. All
      NAD(P)H oxidase subunits were present in HVSMCs as detected by reverse
      transcriptase-polymerase chain reaction and immunoblotting. Ang II increased
      NAD(P)H oxidase subunit abundance. These effects were inhibited by cycloheximide.
      Acute Ang II stimulation (10 to 15 minutes) increased p47phox serine
      phosphorylation and induced p47phox and p67phox translocation. This was
      associated with NAD(P)H oxidase activation. In cells transfected with gp91phox
      antisense oligonucleotides, Ang II-mediated actions were abrogated. NADPH-induced
      superoxide generation was reduced by gp91ds-tat and apocynin, inhibitors of
      p47phox-gp91phox interactions. Our results suggest that HVSMCs possess a
      functionally active gp91phox-containing neutrophil-like NAD(P)H oxidase. Ang II
      regulates the enzyme by inducing phosphorylation of p47phox, translocation of
      cytosolic subunits, and de novo protein synthesis. These novel findings provide
      insight into the molecular regulation of NAD(P)H oxidase by Ang II in HVSMCs.
      Furthermore, we identify differences in gp91phox homologue expression in VSMCs
      from rats and human small and large arteries.

PMID- 12065325
TI  - Myosin light chain phosphorylation in neutrophil-stimulated coronary
      microvascular leakage.
AB  - Neutrophil-induced coronary microvascular leakage represents an important
      pathophysiological consequence of ischemic and inflammatory heart diseases. The
      precise mechanism by which neutrophils regulate endothelial barrier function
      remains to be established. The aim of this study was to examine the microvascular
      endothelial response to neutrophil activation with a focus on myosin light chain
      kinase (MLCK)-mediated myosin light chain (MLC) phosphorylation, a regulatory
      process that controls cell contraction. The apparent permeability coefficient of
      albumin (Pa) was measured in intact isolated porcine coronary venules. Incubation
      of the vessels with C5a-activated neutrophils induced a time- and concentration
      dependent increase in Pa. The hyperpermeability response was significantly
      attenuated during inhibition of endothelial MLC phosphorylation with the
      selective MLCK inhibitor ML-7 and transfection of a specific MLCK-inhibiting
      peptide. In contrast, transfection of constitutively active MLCK elevated Pa,
      which was abolished by ML-7. In addition to the vessel study, albumin
      transendothelial flux was measured in cultured bovine coronary venular
      endothelial monolayers, which displayed a hyperpermeability response to
      neutrophils and MLCK in a pattern similar to that in venules. Importantly,
      neutrophil stimulation caused MLC phosphorylation in endothelial cells in a time
      course closely correlated with that of the hyperpermeability response.
      Consistently, the MLCK inhibitors abolished neutrophil-induced MLC
      phosphorylation. Furthermore, immunohistochemical observation of neutrophil
      stimulated endothelial cells revealed an increased staining for phosphorylated
      MLC in association with contractile stress fiber formation and intercellular gap
      development. Taken together, the results suggest that endothelial MLCK activation
      and MLC phosphorylation play an important role in mediating endothelial barrier
      dysfunction during neutrophil activation.

PMID- 12065327
TI  - Obstructive sleep apnea: asleep in our consciousness no more.

PMID- 12065326
TI  - Insulin-like growth factor-1 enhances inflammatory responses in endothelial
      cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation
      and adhesion molecule expression.
AB  - Insulin-like growth factor (IGF)-1 and the type I IGF-1 receptor are important
      regulators of vascular function that may contribute to cardiovascular disease. We
      hypothesized that IGF-1 causes endothelial cell dysfunction and expression of
      neutrophil and monocyte adhesion molecules by enhancing pro-inflammatory cytokine
      signal transduction. Long-term IGF-1 treatment of endothelial cells potentiated c
      Jun and nuclear factor NF-kappaB activation by tumor necrosis factor (TNF)-alpha
      and enhanced TNF-alpha-mediated adhesion molecule expression. In response to IGF
      1 treatment, the expression of kinases in the c-Jun/c-Jun NH(2)-terminal kinase
      signaling pathway (MEKK1, MEK4, and JNK1/2) was unchanged, but expressions of
      insulin receptor substrate-1 and Grb2-associated binder-1 (Gab1) were
      significantly decreased. Because Gab1 is involved in both c-Jun and NF-kappaB
      activation by TNF-alpha, we focused on Gab1-dependent signaling. Gab1 inhibited c
      Jun and NF-kappaB transcriptional activation by TNF-alpha. Interestingly, Gab1
      inhibited c-Jun transcriptional activity induced by MEKK3 but not MEKK1 and MEK4.
      Gab1 associated with MEKK3, and a catalytically inactive form of MEKK3 inhibited
      TNF-alpha-induced c-Jun and NF-kappaB transcriptional activation, suggesting a
      critical role for Gab1 and MEKK3 in TNF-alpha signaling. These data demonstrate
      that Gab1 and MEKK3 play important roles in endothelial cell inflammation via
      regulating the activation of c-Jun and NF-kappaB. Furthermore, the IGF-1-mediated
      downregulation of Gab1 expression represents a novel mechanism to promote
      vascular inflammation and atherosclerosis.

PMID- 12065328
TI  - Is the relationship between obstructive sleep apnea and gastroesophageal reflux
      clinically important?

PMID- 12065329
TI  - Challenges of treating latent tuberculosis infection.

PMID- 12065330
TI  - Oral vs inhaled corticosteroids following emergency department discharge of
      patients with acute asthma.

PMID- 12065331
TI  - Predicting outcome in primary graft failure.

PMID- 12065332
TI  - The anarchy of weaning techniques.

PMID- 12065333
TI  - Increased physician-reported sleep apnea: the National Ambulatory Medical Care
      Survey.
AB  - BACKGROUND: Despite increased recognition of sleep apnea as a major health
      problem, little is known about physician practice patterns regarding this
      condition. METHODS: We used the National Ambulatory Medical Care Survey (NAMCS)
      data between the years of 1990 to 1998, a weighted estimate of the frequency of
      physicians' diagnoses nationwide in their outpatient practices, to address the
      following questions: (1) has there been an increase in physician reporting of
      sleep apnea, (2) which physicians reported diagnoses of sleep apnea, and (3) what
      are the demographic characteristics of patients with diagnoses of sleep apnea?
      RESULTS: During this 9-year period, there was a 12-fold increase in the diagnosis
      of sleep apnea in outpatients, from 108,121 to 1,305,624 diagnoses (p < 0.001).
      Among other primary sleep disorders, only insomnia had an increase in reporting
      (fourfold, p < 0.001). Report of sleep apnea was greatest among primary care
      providers (37%), pulmonologists (24%), and otolaryngologists (18%). Sleep apnea
      was reported more often in men than in women (3:1, respectively), and 80% of
      diagnoses occurred in the following age groups: 30 to 39 years (12%), 40 to 49
      years (33%), 50 to 59 years (27%), and 60 to 69 years (12%). Conditions
      associated with sleep apnea included hypertension (10%), obesity (6%), and COPD
      (7%). Increased reporting of sleep apnea by NAMCS physicians was associated with
      increases in the number of accredited sleep laboratories and the number of sleep
      publications in the medical literature during the period of review (p < 0.001).
      CONCLUSION: Sleep apnea is recognized increasingly by physicians. Further
      investigation is necessary to define those factors that influence physician
      recognition and reporting of sleep apnea, and approaches associated with optimum
      patient outcomes.

PMID- 12065334
TI  - Symptomatic gastroesophageal reflux in subjects with a breathing sleep disorder.
AB  - STUDY OBJECTIVES: A link between gastroesophageal reflux (GER) and obstructive
      sleep apnea (OSA) has been suggested; however, the prevalence and frequency of
      symptomatic GER and the influence of OSA severity on GER are not known. DESIGN
      AND PATIENTS: Two hundred seventy-one subjects referred for overnight sleep
      studies were investigated for subjects with a breathing sleep disorder,
      occurrence of symptomatic GER, potential risk factors for both conditions, and
      comorbidity using a validated questionnaire. RESULTS: Overall, 160 of the 228
      respondents (73%; 135 subjects with OSA and 93 subjects who snore) reported GER
      related symptoms, with heartburn and/or acid regurgitation being the leading
      symptoms. No evidence of a difference in the occurrence of symptomatic GER
      between subjects who snore and subjects with OSA was observed (odds ratio [OR],
      1.21; 95% confidence interval [CI], 0.7 to 2.1). Furthermore, the occurrence of
      reflux symptoms was not influenced by the severity of OSA (OR per 10 4% arterial
      oxygen saturation [SaO(2)] dips per hour, 0.98; 95% CI, 0.8 to 1.1). Self
      reported comorbidity was higher in subjects with OSA compared with subjects who
      snore (p = 0.02), but none of the potential risks produced an association with
      the presence of reflux symptoms in this sample of patients with a breathing sleep
      disorder. CONCLUSION: We conclude that symptomatic GER is common in subjects with
      a breathing sleep disorder, but there was no difference between those with OSA
      and subjects who snore.

PMID- 12065335
TI  - Factors affecting the incidence of Stenotrophomonas maltophilia isolation in
      cystic fibrosis.
AB  - STUDY OBJECTIVES: To identify factors predisposing cystic fibrosis (CF) patients
      to Stenotrophomonas maltophilia infection and to determine whether coinfection
      with S maltophilia affects the clinical response to therapy with tobramycin
      solution for inhalation (TSI), 300 mg bid. DESIGN: Retrospective review of data
      collected from two identical, 6-month, randomized, placebo-controlled trials.
      SETTING: Sixty-nine CF centers in the United States. INTERVENTIONS: Active drug
      administration of 300 mg TSI. PATIENTS: Five hundred twenty CF patients with
      chronic Pseudomonas aeruginosa endobronchial infections. MEASUREMENTS AND
      RESULTS: A logistic regression analysis identified factors contributing to
      increased S maltophilia isolation frequency. In this multivariate analysis, the
      only significant predictors of S maltophilia isolation during the last month of
      the trial were the concomitant use of oral quinolones (primarily ciprofloxacin; p
      = 0.0015) and S maltophilia isolation prior to treatment (p < 0.0001). Treatment
      group, gender, age, use of systemic or inhaled steroids, use of oral sulfonamide,
      IV cephalosporins, or penicillin antibiotics, baseline FEV(1) percent predicted,
      and pretreatment Aspergillus isolation were not significant predictors of
      subsequent S maltophilia infection. In addition, S maltophilia-positive culture
      frequency was compared to the change in pulmonary function. Patients who either
      never had culture results positive for S maltophilia or who were positive at <25%
      of observations had greater clinical response to TSI at the final study visit
      compared to patients who were positive at > or = 25% of observations.
      CONCLUSIONS: TSI therapy did not result in a greater risk for isolation of S
      maltophilia than standard care alone. In contrast, oral quinolone antibiotic use
      during the trial was associated with a 2.7-fold increased risk of having a
      culture positive for S maltophilia (p = 0.0015). The use of TSI to suppress P
      aeruginosa resulted in improved lung function, regardless of S maltophilia
      culture frequency. However, improvement was not as great among patients who were
      persistently coinfected with S maltophilia.

PMID- 12065336
TI  - Use of the gas exchange threshold to noninvasively determine the lactate
      threshold in patients with cystic fibrosis.
AB  - OBJECTIVE: The anaerobic threshold (AT) is a submaximal index related to
      endurance exercise performance, which is usually determined by the measurement of
      blood lactate concentration during an incremental exercise test (lactate
      threshold [LT]). The LT, and thus the AT, can also be detected noninvasively in
      normal subjects by means of the gas exchange threshold (GET). This study was
      undertaken to validate the use of GET in patients with cystic fibrosis (CF) with
      a wide range of disease severity, and to assess the reproducibility of this
      index. METHODS: In patients with CF (FEV(1) range, 23 to 118% of predicted) and
      control subjects, gas exchange was measured breath by breath during the
      incremental exercise tests to allow determination of the GET. Arterialized-venous
      blood was sampled for determination of the LT. The GET and LT were determined in
      a blinded manner. RESULTS: The mean differences (GET - LT) for control subjects
      (n = 18) and patients with CF (n = 23) were - 40 mL/min and + 10 mL/min,
      respectively, neither being significantly different from zero. The limits of
      agreement were +/- 550 mL/min and +/- 410 mL/min, respectively. The mean test
      retest differences in GET for control subjects (n = 14) and patients with CF (n =
      12) were - 50 mL/min and 0 mL/min, respectively, neither being significantly
      different from zero; the respective limits of reproducibility were +/- 450 mL/min
      and +/- 350 mL/min. CONCLUSIONS: This study demonstrates that in patients with
      CF, the GET can be used to obtain an unbiased estimate of the LT, and that the
      GET is reproducible.

PMID- 12065337
TI  - Cost-effectiveness of tuberculosis prophylaxis after release from short-term
      correctional facilities.
AB  - BACKGROUND: There is poor adherence with tuberculosis preventive therapy among
      patients released from short-term correctional facilities, leading to
      recommendations against screening for latent tuberculosis infection (LTBI) in
      this setting. OBJECTIVES: To assess adherence to isoniazid preventive therapy
      (IPT) following release from short-term correctional facilities, and to estimate
      the cost-effectiveness of this practice. METHODS: Records of individuals referred
      for IPT from the Connecticut Department of Corrections to the City of Hartford
      Chest Clinic between January 1993 and June 1997 were reviewed. The data
      abstracted included demographics, adherence to IPT, and the duration of IPT
      completed before release from prison. An analysis was performed to determine the
      cost-effectiveness of this program. RESULTS: A total of 168 records were
      reviewed. The mean duration of IPT completed before release from prison was 8
      weeks. Eighty-six subjects (57%) never came to clinic after release. Of the 64
      subjects (43%) who attended clinic at least once, 35 subjects (55%) completed IPT
      and 29 subjects (45%) were unavailable for follow-up before completing therapy.
      Thirty-three of the 64 subjects (52%) who attended the clinic had to be restarted
      on IPT due to a prolonged lapse in therapy prior to the first visit. We estimate
      that $32,866 was spent on this program, but $42,093 in future costs associated
      with reactivation tuberculosis was prevented. CONCLUSIONS: Adherence with IPT is
      poor in patients released from short-term correctional facilities. Nonetheless,
      this program was cost-effective. An alternative strategy may be to screen for
      LTBI among inmates of short-term correctional facilities but withhold IPT in
      inmates expected to be released before therapy would be completed. Instead, these
      inmates could be referred to an appropriate clinic after release. Prophylaxis may
      be started in subjects who keep an initial clinic appointment after release.

PMID- 12065338
TI  - Clinical presentation of community-acquired Chlamydia pneumoniae pneumonia in
      adults.
AB  - STUDY OBJECTIVE: To investigate the clinical presentation of community-acquired
      Chlamydia pneumoniae pneumonia in adults. DESIGN: Prospective study. SETTING:
      Kawasaki Medical School Hospital, Kawasaki Medical School Kawasaki Hospital, and
      Kurashiki Daiichi Hospital in Japan. PARTICIPANTS: Forty patients with community
      acquired pneumonia with C pneumoniae as the only pathogen identified admitted to
      three hospitals between April 1996 and March 2001 and their clinical
      presentations were compared to patients with Streptococcus pneumoniae and
      Mycoplasma pneumoniae pneumonia. MEASUREMENTS: The diagnosis of C pneumoniae
      infection was based on isolation and serologic testing of antibodies by the
      microimmunofluorescence test. RESULTS: The clinical presentations, except for
      shortness of breath, were similar for the three major etiologic agents. The mean
      temperature of C pneumoniae patients on hospital admission was 37.9 degrees C,
      which was lower than that of patients with S pneumoniae and M pneumoniae. The
      mean WBC count on hospital admission was lower in the patients with C pneumoniae
      (mean, 9,100/microL) than in those with S pneumoniae pneumonia but higher than in
      those with M pneumoniae pneumonia. No patients required respiratory support or
      admission to an ICU, and no deaths occurred among the C pneumoniae pneumonia
      patients. CONCLUSIONS: Our results indicate that C pneumoniae pneumonia as a
      single etiologic agent is mild and that the underlying conditions and clinical
      symptoms closely resemble those of S pneumoniae pneumonia. However, the physical
      examinations, laboratory findings, and prognostic factors of the C pneumoniae
      patients resembled those of patients with M pneumoniae pneumonia.

PMID- 12065339
TI  - Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of
      clarithromycin.
AB  - STUDY OBJECTIVES: To determine the effect of clarithromycin therapy in patients
      with asthma. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING:
      A tertiary referral center. PATIENTS OR PARTICIPANTS: Fifty-five subjects with
      chronic, stable asthma recruited from the general Denver, CO, community.
      INTERVENTIONS: Patients underwent airway evaluation for Mycoplasma pneumoniae and
      Chlamydia pneumoniae by polymerase chain reaction (PCR) and culture, followed by
      treatment with clarithromycin, 500 bid, or placebo for 6 weeks. MEASUREMENTS AND
      RESULTS: Outcome variables were lung function, sinusitis as measured by CT, and
      the inflammatory mediators tumor necrosis factor (TNF)-alpha, interleukin (IL)-2,
      IL-4, IL-5, and IL-12 messenger RNA (mRNA) measured via in situ hybridization, in
      airway biopsies, and BAL. Mycoplasma or chlamydia were detected by PCR in 31 of
      55 asthmatics. Treatment resulted in a significant improvement in the FEV(1), but
      only in the PCR-positive subjects (2.50 +/- 0.16 to 2.69 +/- 0.19 L, mean +/-
      SEM; p = 0.05). This was not appreciated in the PCR-negative subjects (2.59 +/-
      0.24 to 2.54 +/- 0.18 L, p = 0.85) or the PCR-positive or PCR-negative subjects
      who received placebo. Sinus CTs revealed no change in sinusitis with
      clarithromycin treatment. In situ hybridization revealed no significant
      difference in baseline airway tissue or BAL-mediator expression between the PCR
      positive and PCR-negative subjects. However, the PCR-positive subjects who
      received clarithromycin demonstrated a reduction in TNF-alpha (p = 0.006), IL-5
      (p = 0.007), and IL-12 (p = 0.004) mRNA in BAL and TNF-alpha mRNA in airway
      tissue (p = 0.0009). The PCR-negative subjects who received clarithromycin only
      demonstrated a reduction in TNF-alpha (p = 0.01) and IL-12 (p = 0.002) mRNA in
      BAL and TNF-alpha mRNA in airway tissue (p = 0.004). There were no significant
      differences in cytokine expression in those subjects who received placebo.
      CONCLUSIONS: These observations support the hypothesis that clarithromycin
      therapy improves lung function, but only in those subjects with positive PCR
      findings for M pneumoniae or C pneumoniae.

PMID- 12065340
TI  - Impact of a bronchiolitis guideline: a multisite demonstration project.
AB  - STUDY OBJECTIVES: The purpose of this study was to determine the impact of a
      multisite implementation of an evidence-based clinical practice guideline for
      bronchiolitis. DESIGN: Before and after study. SETTING: Eleven Child Health
      Accountability Initiative (CHAI) study hospitals. PATIENTS: Children < 12 months
      of age with a first-time episode of bronchiolitis. INTERVENTION: The guideline
      was implemented in December 1998. Complete preimplementation and
      postimplementation administrative data on hospital admissions, resource
      utilization, and length of stay were available from seven study hospitals. At
      five sites, chart reviews were conducted for data on the number and type of
      bronchodilators used. MEASUREMENTS AND RESULTS: Complete administrative data were
      available for 846 historical control subjects and 792 study patients. Length of
      stay decreased significantly. While the proportion of eligible patients who
      received any bronchodilator did not change (84%), the proportion of patients who
      received albuterol decreased from 80 to 75% after guideline implementation (p <
      0.03). For patients who received bronchodilators, the mean (+/- SD) number of
      doses decreased from 13.6 +/- 14.0 to 7.3 +/- 9.1 doses (p < 0.0001). For
      patients who received albuterol, the mean number of doses decreased from 12.8 +/-
      11.8 to 6.4 +/- 7.8 doses (p < 0.0001). Other resource use decreased modestly.
      Hospital readmission rates within 7 days of discharge were unchanged.
      CONCLUSIONS: We successfully extended the implementation of an evidence-based
      clinical practice guideline from one hospital to seven hospitals. Within just a
      single bronchiolitis season, some significant changes in practice were seen. The
      multisite CHAI collaborative appears to be a promising laboratory for large-scale
      quality improvement initiatives.

PMID- 12065341
TI  - Replacement of oral corticosteroids with inhaled corticosteroids in the treatment
      of acute asthma following emergency department discharge: a meta-analysis.
AB  - OBJECTIVES: Oral corticosteroids (CS) are standard treatment for patients
      discharged from the emergency department (ED) after treatment for acute asthma.
      Several recent, relatively small trials have investigated the replacement of CS
      with inhaled corticosteroids (ICS), with varied results and conclusions. This
      systematic review examined the effect of using ICS in place of CS on outcomes in
      this setting. METHODS: Only randomized controlled trials were eligible for
      inclusion. Studies in which patients were treated for acute asthma in the ED or
      its equivalent, and on discharge compared ICS therapy to standard CS therapy,
      were eligible for inclusion. Trials were identified using the Cochrane Airways
      Review Group register, searching abstracts and bibliographies, and contacting
      primary authors and pharmaceutical companies. Data were extracted and
      methodologic quality assessed independently by two reviewers, and missing data
      were obtained from authors. RESULTS: Seven trials, involving a total of 1,204
      patients, compared high-dose ICS therapy vs CS therapy after ED discharge. There
      were no significant differences demonstrated between the treatments for relapse
      rates (odds ratio, 1.00; 95% confidence interval, 0.66 to 1.52) or in the
      secondary outcomes of beta-agonist use, symptoms, or adverse events. However, the
      sample size was not adequate to prove equivalence between the treatments, and
      severe asthmatics were excluded from these trials. CONCLUSIONS: There is some
      evidence that high-dose ICS therapy alone may be as effective as CS therapy when
      used in mild asthmatics on ED discharge; however, there is a significant
      possibility of a type II error in drawing this conclusion.

PMID- 12065342
TI  - Airway dehydration: a therapeutic target in asthma?
AB  - BACKGROUND: Airway dehydration triggers exercise-induced bronchoconstriction in
      virtually all patients with active asthma. We are not aware of any investigations
      of airway dehydration in patients with naturally occurring asthma exacerbations.
      We wish to investigate whether airway dehydration occurs in acute asthmatic
      patients in the emergency department, and its functional significance. METHODS:
      In a pilot study on 10 asthmatic patients and 10 control subjects in the
      emergency department, respiratory rate was counted manually, and relative
      humidity of expired air was recorded using an air probe hygrometer. In parallel
      laboratory studies carried out over 2 consecutive days, 19 asthmatics and 10
      control subjects were challenged initially with dry air, and on the second day
      with humidified air. FEV(1) and humidity measurements were made immediately
      before and after the tachypnea challenges. RESULTS: In the emergency department,
      the asthmatic group was more tachypneic (p < 0.0001) and their expired air was
      drier (p < 0.0001) than the control group. Following a dry-air tachypnea
      challenge in the laboratory, which caused dehydration of the expired air in all
      subjects, half of the asthmatics, but none of the control subjects, demonstrated
      a fall of > 10% in FEV(1) from baseline. This bronchoconstriction was prevented
      by humidifying the inspired air; tachypnea with no water loss did not affect lung
      function in asthmatic subjects. CONCLUSIONS: Dehydration of the expired air is
      present in asthmatic patients in the emergency department. The
      bronchoconstriction triggered by dry-air tachypnea challenge in the laboratory
      can be prevented by humidifying the inspired air. Airway rehydration merits
      further investigation as a potential adjunct to acute treatment of asthma
      exacerbations.

PMID- 12065343
TI  - Safety of a cyclooxygenase-2 inhibitor in patients with aspirin-sensitive asthma.
AB  - BACKGROUND: In 5 to 10% of adult patients with asthma, aspirin (acetylsalicylic
      acid [ASA]) and most other nonsteroidal anti-inflammatory drugs (NSAIDs)
      precipitate acute asthmatic attacks. Therefore, choosing an alternative anti
      inflammatory agent for patients with adverse reactions to an NSAID is a common
      problem in clinical practice. The discoveries that cyclooxygenase (COX)-2 is an
      inducible form of COX that is involved in inflammation and that COX-1 is the
      major isoform responsible for the production of prostaglandins have provided a
      reasonable basis for the development of specific COX-2 inhibitors as a new class
      of anti-inflammatory agents. OBJECTIVE: The purpose of this study was to
      demonstrate that rofecoxib, a specific inhibitor of COX-2, does not cause
      asthmatic attacks in patients with ASA and/or other NSAID-induced asthma.
      METHODS: We studied 40 patients, all of whom had experienced asthma induced by at
      least two different NSAIDs. The patients were challenged in a single-blind manner
      with different doses of rofecoxib on 3 different days, until either the
      therapeutic dose of 25 mg or intolerance was reached. Each patient was
      rechallenged with 25 mg of rofecoxib 7 days later if no evidence of intolerance
      had been observed previously. RESULTS: Rofecoxib, 25 mg, was proven to be well
      tolerated in all 40 patients with ASA-induced and NSAID-induced asthma.
      CONCLUSION: Our study appears to demonstrate that rofecoxib is a suitable NSAID
      for treatment of patients with ASA and/or other NSAID-induced asthma.

PMID- 12065344
TI  - Pulmonary function characteristics in patients with different patterns of
      methacholine airway hyperresponsiveness.
AB  - STUDY OBJECTIVES: The American Thoracic Society guidelines for methacholine
      induced airway hyperresponsiveness include a > or = 20% reduction in FEV(1) or a
      > or = 40% reduction in specific airway conductance (sGaw). The objectives of the
      current study are to assess the concordance between these two criteria and to
      characterize the pulmonary function and respiratory symptoms of patients with
      different patterns of methacholine hyperresponsiveness. STUDY DESIGN: A
      prospective study of 248 consecutive patients referred for methacholine
      bronchoprovocation testing. RESULTS: Positive methacholine hyperresponsiveness
      was noted in 179 patients; 139 patients (78%) had a > or = 20% reduction in
      FEV(1), whereas 40 patients (22%) had a > or = 40% reduction in sGaw alone
      without a significant change in FEV(1). The former group had the following: (1)
      higher baseline lung volumes, (2) lower baseline values of FEV(1) and sGaw, (3)
      forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75))/FVC
      ratios compared to patients with a reduction in sGaw alone (0.72 +/- 0.26 vs 0.97
      +/- 0.28, mean +/- SD; p < 0.0001), and (4) more frequent presence of wheezing
      and chest tightness (p < 0.05). CONCLUSIONS: First, a substantial number of
      patients have a reduction in SGaw alone in response to methacholine, and
      secondly, this response is seen in patients with a higher FEF(25-75)/FVC ratio.
      Since the FEF(25-75)/FVC ratio is thought to be an index of airway size relative
      to lung size, we speculate that the larger intrinsic airway size relative to lung
      size may explain the differences in baseline parameters and patterns of
      methacholine hyperresponsiveness.

PMID- 12065345
TI  - Clinically important improvements in asthma-specific quality of life, but no
      difference in conventional clinical indexes in patients changed from conventional
      beclomethasone dipropionate to approximately half the dose of extrafine
      beclomethasone dipropionate.
AB  - STUDY OBJECTIVE: Clinical trials of asthma treatments usually use measures of
      asthma control to assess efficacy. However, it is also important to determine
      whether patients themselves benefit from interventions. The aim of this study was
      to evaluate health-related quality of life in patients with asthma switched from
      conventional chlorofluorocarbon (CFC) beclomethasone dipropionate (BDP) to
      hydrofluroalkane-134a (HFA) BDP extrafine aerosol at half the daily dose. DESIGN:
      Open-label, 12-month, parallel-group, randomized trial. SETTING: Fifty-seven
      centers in four countries (United States, Belgium, the Netherlands, and United
      Kingdom). PATIENTS: Four hundred seventy-three patients with a > or = 6-month
      history of asthma, stable symptoms, and maintained on CFC-BDP, 400 to 1,600
      microg/d. INTERVENTIONS: HFA-BDP, 200 to 800 microg/d (n = 354), or CFC-BDP, 400
      to 1,600 microg/d (n = 119). MEASUREMENTS AND RESULTS: The Asthma Quality of Life
      Questionnaire (AQLQ) and pulmonary function tests were completed at months 0, 2,
      4, 8, and 12. For 1 month before each visit, patients made daily recordings of
      symptoms, peak expiratory flow, and beta(2)-agonist use. Two hundred ninety-six
      patients completed the study (HFA-BDP, 83.6%; CFC-BDP, 83.2%). At month 12,
      improvements in overall AQLQ scores were greater in the HFA-BDP group than in the
      CFC-BDP group (p = 0.0024). The number of patients who need to be treated with
      HFA-BDP for one to have a clinically important improvement in overall asthma
      specific quality of life compared with CFC-BDP was 7.3. There was no evidence of
      differences (p > 0.05) between treatment groups for airway caliber, symptoms, or
      beta(2)-agonist use. CONCLUSION: Clinically important improvements in the AQLQ
      score were observed at month 12 for HFA-BDP vs CFC-BDP, while conventional
      clinical indexes of pulmonary function and asthma control were similar in the two
      groups.

PMID- 12065346
TI  - Understanding and use of inhaler medication by asthmatics in specialty care in
      Trinidad: a study following development of Caribbean guidelines for asthma
      management and prevention.
AB  - STUDY OBJECTIVES: Following the development of the Caribbean Guidelines for
      Asthma Care, we examined the utilization of inhaled medications in asthmatic
      patients in Trinidad, West Indies. SETTING: Chest Clinic, Ministry of Health,
      Trinidad. PARTICIPANTS: Physician-diagnosed asthmatic patients who attended the
      Chest Clinic between July 1998 and August 2000. MEASUREMENTS AND RESULTS: A
      consecutive sample of patients who were > 7 years of age (n = 402) was
      interviewed about compliance with, understanding of, and use of inhaler
      medication. The inhaler technique of these patients was directly observed.
      Inhaled steroid therapy was prescribed in 83% of patients but were prescribed the
      least in elderly patients (63%) and children (62%). Salbutamol was prescribed in
      98% of patients, and ipratropium and sodium cromoglycate were selectively
      prescribed in elderly men and children, respectively. Only 33% of patients used
      the inhaler correctly, and children and the elderly were the least efficient in
      its use. The use of a spacer device was advised in 19% of patients, including
      only 6% of the elderly patients. Explanations for different inhaler therapies
      were given to 62% of patients, and 53% of patients could describe these reasons.
      The reported 40% noncompliance rate among patients in the sample was primarily a
      result of long waiting periods at the pharmacy (58%) and the personal cost
      incurred on purchasing the medication (52%). CONCLUSIONS: Educating patients,
      with a focus on children and the elderly, in inhaler techniques and reinforcing
      understanding of asthma medications can improve asthma management in Trinidad.
      Asthma caregivers in the Caribbean should ensure the appropriate dissemination of
      the guidelines and should outline strategies for their implementation.

PMID- 12065347
TI  - Asthma and COPD among aboriginals in Alberta, Canada.
AB  - BACKGROUND: Aboriginals in Canada bear a disproportionately higher burden of some
      chronic illnesses than nonaboriginals. Although there is a greater prevalence of
      smoking, poor housing, and overcrowding in aboriginal than nonaboriginal
      communities, the rates of office and emergency visits for asthma and COPD among
      aboriginals are not well known. STUDY OBJECTIVE: To determine whether aboriginals
      require higher rates of asthma and COPD emergency and office visits than
      nonaboriginals. SETTING: Population-based cohort of people residing in Alberta,
      Canada (population 2.8 million) between April 1, 1996, and March 31, 1997.
      DESIGN: Retrospective cohort study. RESULTS: We observed that aboriginals were
      2.1 times (95% confidence interval [CI], 2.0 to 2.2) and 1.6 times (95% CI, 1.6
      to 1.6) more likely to have an emergency and office visit for asthma or COPD,
      respectively, when compared to age-matched and sex-matched nonaboriginals.
      However, they were 55% (95% CI, 52 to 58%) less likely to see a specialist and
      66% (95% CI, 63 to 70%) less likely to undergo spirometry than nonaboriginals.
      CONCLUSIONS: These findings indicate that aboriginals bear a disproportionately
      higher burden of asthma and COPD than nonaboriginals. However, lower use of
      spirometry and specialist services suggests that there might be access barriers
      to quality health care for aboriginals in Canada.

PMID- 12065348
TI  - Analysis of exhaled nitric oxide by the helium bolus method.
AB  - STUDY OBJECTIVES: The precise anatomic sites contributing to exhaled nitric oxide
      (eNO) are still unknown. The present study was designed to analyze profiles of
      eNO by referring to the He exhalation curve and examining the effects of breath
      holding and expiratory flow rates on eNO. PARTICIPANTS: Healthy volunteers and
      patients with stable asthma. MEASUREMENTS AND RESULTS We used the He bolus method
      of the closing volume, and simultaneously analyzed the concentrations of exhaled
      He and nitric oxide (NO). By referring to the He exhalation curve, the expired
      gas was divided into three parts: airway dead space (phase 1), a mixture of
      airway and alveolar gas (phase 2), and alveolar gas (phase 3 and phase 4). The
      eNO profiles showed a peak in phase 2 (peak eNO) and decreased gradually to a
      plateau in the latter half of phase 3 (plateau eNO). The levels of peak eNO were
      higher than those of plateau eNO in both normal subjects and asthmatic patients.
      Breath-holding increased levels of peak eNO 2.5-fold in both normal subjects and
      asthmatic patients, but it did not affect the levels of plateau eNO. The levels
      of peak eNO increased as the expiratory flow rate decreased, and the levels of
      plateau eNO showed a similar flow dependency. CONCLUSION: A peak value of eNO
      concentration profiles may directly express the production of NO in the airway.

PMID- 12065349
TI  - Exhaled nitric oxide and bronchial responsiveness to adenosine 5'-monophosphate
      in subjects with allergic rhinitis.
AB  - STUDY OBJECTIVES: To determine differences in exhaled nitric oxide (ENO) between
      subjects with allergic rhinitis with and without increased responsiveness to
      direct and indirect bronchoconstrictor agents. STUDY DESIGN: Cross-sectional
      study with the order of challenge tests randomized. SETTING: Specialist allergy
      unit in a university hospital. PATIENTS: Thirty-eight subjects without asthma
      with allergic rhinitis and 10 healthy nonatopic control subjects. MEASUREMENTS
      AND RESULTS: Participants were challenged with increasing concentrations of
      adenosine 5'monophosphate (AMP) and methacholine. ENO was measured with the
      single-exhalation method. A positive response to both bronchoconstrictor agents
      was detected in nine subjects with allergic rhinitis, whereas four subjects
      showed increased responsiveness to AMP but not to methacholine. The geometric
      mean (range) ENO values were significantly higher in subjects with allergic
      rhinitis with increased responsiveness to either methacholine or AMP than in
      subjects with normal responsiveness to both agonists: 51.3 parts per billion
      (ppb) [22.0 to 108.5 ppb] vs 25.1 ppb (5.7 to 102.9 ppb, respectively; p = 0.007)
      and healthy control subjects (11.2 ppb [5.0 to 31.9 ppb], p < 0.001). Subjects
      with allergic rhinitis with normal responsiveness to both agonists also had
      higher concentrations of ENO than healthy control subjects (p = 0.007). No
      correlation was found between ENO and either of the provocative concentrations of
      methacholine or AMP causing a 20% fall in FEV(1). CONCLUSIONS: In subjects
      without asthma but with allergic rhinitis, the presence of bronchoconstriction in
      response to methacholine or AMP is associated with increased ENO concentrations.
      However, elevated concentrations of ENO are detected even in subjects with
      allergic rhinitis without airway hyperresponsiveness. These results suggest that
      the presence of airway hyperresponsiveness is not the only factor that determines
      the increased NO levels detected in subjects with allergic rhinitis.

PMID- 12065350
TI  - Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in
      patients with pulmonary arterial hypertension: open-label pilot study.
AB  - STUDY OBJECTIVES: To evaluate the safety and efficacy of sitaxsentan, an
      endothelin-A receptor antagonist, in a 12-week, open-label trial of patients with
      pulmonary arterial hypertension (PAH). PATIENTS: Six children and 14 adults with
      New York Heart Association (NYHA) functional class II, III, or IV primary
      pulmonary hypertension or PAH associated with either congenital systemic-to
      pulmonary shunts or collagen vascular disease were enrolled. MEASUREMENTS:
      Sitaxsentan was administered orally at 100 to 500 mg bid for 12 weeks.
      Cardiopulmonary hemodynamics via cardiac catheterization were obtained at
      baseline and week 12. Six-minute walk test distance was measured at baseline,
      week 6, and week 12. RESULTS: Sitaxsentan treatment resulted in significant
      improvement in exercise capacity as assessed by the 6-min walk distance (baseline
      [mean +/- SD], 466 +/- 132 m; week 12, 515 +/- 141 m, n = 20, p = 0.006). Mean
      pulmonary artery pressure and pulmonary vascular resistance index also improved
      (63 +/- 20 to 52 +/- 22 mm Hg, n = 17, p = 0.0002; and 20 +/- 11 to 14 +/- 13 U x
      m(2), n = 17, p = 0.008, respectively). Serious adverse events included two cases
      of acute hepatitis (fatal in one patient). CONCLUSIONS: Patients with NYHA
      functional class II, III, or IV PAH showed a significant improvement in exercise
      capacity and cardiopulmonary hemodynamics over a 12-week period of treatment with
      sitaxsentan, an endothelin-A receptor antagonist. Further investigation is
      warranted to evaluate the safety and efficacy of sitaxsentan in patients with
      PAH.

PMID- 12065351
TI  - Arterial oxygenation associated with portopulmonary hypertension.
AB  - STUDY OBJECTIVES: To characterize arterial oxygenation in patients referred to
      Mayo Clinic for liver transplantation with a diagnosis of portopulmonary
      hypertension (portoPH). DESIGN: Prospective study. SETTING: Liver transplantation
      program and pulmonary hypertension clinic in a tertiary referral center.
      PARTICIPANTS: Twenty consecutive patients with abnormal pulmonary hemodynamics
      documented by right-heart catheterization (mean pulmonary artery pressure [MPAP]
      > or = 25 mm Hg, pulmonary vascular resistance [PVR] > or = 120 dyne.s.cm(-5),
      and pulmonary capillary wedge pressure [PCWP] < or = 15 mm Hg). Liver transplant
      candidates with normal pulmonary hemodynamics via screening Doppler
      echocardiography (n = 40) served as control subjects. A subgroup of patients
      underwent postural and inspired 100% oxygen blood gas analysis, contrast
      echocardiography, and technetium-labeled macroaggregated albumin ((99m)TcMAA)
      lung/brain scanning to identify and quantitate the degree of intracardiac or
      intrapulmonary shunting. MEASUREMENTS AND RESULTS: portoPH was moderate to severe
      (MPAP > 35 mm Hg) in 18 of 20 patients (90%). Arterial-alveolar oxygen pressure
      gradient (P[A-a]O(2)) was abnormal (> or = 20 mm Hg) in 16 of 20 patients (80%).
      PaO(2) was abnormal (< or = 70 mm Hg) in 3 of 20 patients (15%). Pa0(2) was
      significantly less and P(A-a)O(2) was significantly greater compared to control
      subjects (p < 0.001). All patients had normal (99m)TcMAA brain uptake (< 6%) and
      negative transthoracic contrast echocardiographic findings. No significant
      correlations were found between oxygenation and hemodynamic variables (MPAP, PVR,
      PVR index, and transpulmonary gradient). CONCLUSIONS: Arterial oxygenation
      associated with portoPH was frequently abnormal and significantly worse when
      compared to patients with normal pulmonary hemodynamics by Doppler
      echocardiography. Hypoxemia, as measured by PaO(2) and P(A-a)O(2), was usually
      mild even in the setting of moderate-to-severe portoPH.

PMID- 12065352
TI  - Primary graft failure following lung transplantation: predictive factors of
      mortality.
AB  - STUDY OBJECTIVES: To assess incidence, outcome, and early predictors of mortality
      for patients with primary graft failure (PGF) following lung transplantation
      (LTx), and to develop an injury severity score able to accurately predict ICU
      mortality for these patients. DESIGN: Retrospective cohort analysis. SETTING: Two
      LTx centers in Paris. PATIENTS: Two hundred fifty-nine patients who underwent LTx
      over a 12-year period. MEASUREMENTS AND RESULTS: One hundred thirty-one patients
      (50.6%) met PGF criteria: radiographic graft infiltrate within the first 3 days
      following LTx associated with gas exchange impairment (PaO(2)/fraction of
      inspired oxygen ratio < 300 mm Hg). This syndrome was associated with an
      increased duration of mechanical ventilation (9.1 +/- 1 days vs 3.1 +/- 0.6 days,
      mean +/- SD; p < 0.001) and ICU mortality (29% vs 10.9%; p < 0.01). The patients
      with PGF were randomly assigned to developmental (n = 85) and validation (n = 46)
      samples. Using logistic regression analysis, four variables were found associated
      with ICU mortality in these patients: age, degree of gas exchange impairment,
      graft ischemic time, and severe early hemodynamic failure. An
      ischemia/reperfusion injury severity score was derived using these four
      variables. Model calibration was good in the developmental and validation
      samples, as was model discrimination (area under receiver operating
      characteristic curves, 0.93 and 0.85, respectively). CONCLUSION: PGF following
      LTx is a frequent event, with significant ICU morbidity and mortality. We
      demonstrate that four simple factors allow prediction of ICU mortality with good
      accuracy.

PMID- 12065353
TI  - Bronchiolitis obliterans syndrome after single-lung transplantation: impact of
      time to onset on functional pattern and survival.
AB  - INTRODUCTION: Among risk factors for the progression of bronchiolitis obliterans
      syndrome (BOS) after lung transplantation (LT), the influence of time to BOS
      onset is not known. The aim of the study was to assess if BOS occurring earlier
      after LT is associated with worse functional prognosis and worse graft survival.
      METHOD: We retrospectively compared functional outcome and survival of all single
      LT (SLT) recipients who had BOS develop during follow-up in our center according
      to time to onset of BOS (< 3 years or > or = 3 years after transplantation).
      RESULTS: Among the 29 SLT recipients with BOS identified during the study period,
      20 patients had early-onset BOS and 9 patients had late-onset BOS. The mean
      decline of FEV(1) over time during the first 9 months in patients with early
      onset BOS was significantly greater than in patients with of late-onset BOS (p =
      0.04). At last follow-up, patients with early-onset BOS had a lower mean FEV(1)
      value (25% vs 39% of predicted, p = 0.004), a lower mean PaO(2) value (54 mm Hg
      vs 73 mm Hg, p = 0.0005), a lower 6-min walk test distance (241 m vs 414 m, p =
      0.001), a higher Medical Research Council index value (3.6 vs 1.6, p = 0.0001),
      and a higher percentage of oxygen dependency (90% vs 11%, p = 0.001) compared
      with patients with late-onset BOS. In addition, graft survival of patients with
      early-onset BOS was significantly lower than that of patients with late-onset BOS
      (log-rank test, p = 0.04). There were 18 of 20 graft failures (90%) in the early
      onset BOS group, directly attributable to BOS in all cases (deaths [n = 10] or
      retransplantation [n = 8]). In the late-onset BOS group, graft failure occurred
      in four of nine patients due to death from extrapulmonary causes in three of four
      cases. The median duration of follow-up after occurrence of BOS was not
      statistically different between patients with early-onset BOS and patients with
      late-onset BOS (31 +/- 28 months and 37 +/- 26 months, respectively; p = not
      significant). CONCLUSION: The subgroup of patients who had BOS develop > or = 3
      years after SLT are less likely to have worrisome functional impairment develop
      in long-term follow-up. Considering the balance between the advantages and risks,
      enhancement of immunosuppression should be regarded with more caution in this
      subgroup than in patients with early-onset BOS.

PMID- 12065354
TI  - Risk factors for early mortality and major complications following pneumonectomy
      for non-small cell carcinoma of the lung.
AB  - STUDY OBJECTIVES: To assess the mortality rate and the incidence of
      cardiopulmonary complications after pneumonectomy for non-small cell lung
      carcinoma (NSCLC) and to identify possible associated risk factors. DESIGN:
      Observational study of patients who underwent pneumonectomy. Potential risk
      factors were analyzed from a local database including all thoracic surgical
      cases. SETTING: A university hospital and a chest medical center. PATIENTS AND
      METHODS: From January 1, 1990, to April 30, 2000, 193 consecutive pneumonectomies
      were performed for NSCLC in two affiliated institutions. The following
      information was recorded: demographic, clinical, functional, and surgical
      variables; as well as intraoperative and postoperative events. The risk of
      mortality and cardiopulmonary complications was evaluated using multiple logistic
      regression analysis to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). RESULTS: After undergoing pneumonectomy, all patients were successfully
      extubated in the operating room and then transferred to a postanesthesia care
      unit (126 patients) or ICU (67 patients). The 30-day mortality rate was 9.3%, and
      cardiovascular and/or pulmonary complications occurred in 47% of cases. Coronary
      artery disease (CAD) was a predictor of 30-day mortality (OR, 2.9; 95% CI, 1.1 to
      8.9). Cardiac morbidity (mainly arrhythmias) was significantly related to
      advanced age (OR, 3.7; 95% CI, 1.6 to 8.6) and pathologic stages III/IV (OR, 1.4;
      95% CI, 1.1 to 4.7), whereas continuous epidural analgesia was associated with a
      reduced incidence of respiratory complications (OR, 0.2; 95% CI, 0.1 to 0.6).
      CONCLUSIONS: Pneumonectomy for lung cancer is a high-risk procedure, the risk for
      which is significantly related to the presence of CAD and advanced pathologic
      stages. Importantly, the provision of epidural analgesia contributes to lower the
      risk of respiratory complications.

PMID- 12065355
TI  - Effects of emphysema and lung volume reduction surgery on transdiaphragmatic
      pressure and diaphragm length.
AB  - STUDY OBJECTIVES: To determine the effect of emphysema and lung volume reduction
      surgery (LVRS) on diaphragm length (Ldi) and its capacity to generate
      transdiaphragmatic pressure (Pdi). DESIGN: Prospective clinical trial with a
      parallel group design. SETTING: Laboratory investigations in normal volunteers
      recruited by advertisement and in emphysema outpatients being evaluated for
      elective LVRS. STUDY POPULATION: Thirteen normal subjects and 13 emphysema
      patients matched for age and sex. Six emphysema patients underwent LVRS.
      MEASUREMENTS: Ldi and maximal Pdi during static inspiratory efforts (PdiMax) were
      measured at three different lung volumes (LVs). Pdi during maximal bilateral
      phrenic nerve twitch stimulation (PdiTw) was measured at functional residual
      capacity (FRC). All measurements were repeated at 3, 6, and 12 months
      postoperatively. RESULTS: Ldi, PdiMax, and PdiTw were lower in emphysema patients
      than in normal subjects at their respective LVs. PdiMax and PdiTw at FRC returned
      within the normal range after LVRS in emphysema patients. The relationships
      between PdiMax and LV or Ldi were shifted respectively to higher LV and shorter
      Ldi in emphysema patients relative to normal subjects, both before and after
      LVRS. LVRS effected craniad displacement of the diaphragm but no change in rib
      cage dimensions. Improvements in dyspnea and quality of life after LVRS
      correlated with changes in LV and Ldi but not with changes in airway caliber.
      CONCLUSION: Adaptive mechanisms, consistent with sarcomere deletion, tend to
      restore diaphragm strength in emphysema patients at FRC, which are fully
      expressed after LVRS. Lung remodeling by LVRS may alter pleural surface pressure
      distribution, causing a sustained change in chest wall shape.

PMID- 12065356
TI  - Vocal cord paralysis after surgery for thoracic aortic aneurysm.
AB  - OBJECTIVE: To determine the incidence, etiology, prognosis, and treatment of
      vocal cord paralysis (VCP) after surgery for thoracic aortic aneurysm (TAA).
      STUDY DESIGN: Retrospective study performed between 1989 and 1995. SETTING:
      Academic, tertiary care, referral medical center. PATIENTS: Seventy-one TAA
      patients underwent surgery at the Kameda Medical Center between 1989 and 1995.
      RESULTS: Sixty-two of 71 patients were examined postoperatively for voice
      quality. Twenty patients (32%) had hoarseness develop caused by VCP, as confirmed
      by laryngoscopy. The left recurrent laryngeal nerve had been sacrificed in 1
      patient during surgery, but it was preserved in the remaining 19 patients.
      Unilateral left VCP was noted in 19 patients, and bilateral VCP occurred in 1
      patient. The incidence of VCP was higher in those patients who underwent surgery
      for type I aneurysms (9 of 14 patients, 64%). In 16 of the 19 patients (84%) who
      received follow-up for > 6 months, vocal cord movement did not return to normal.
      Surgery to improve voice quality, arytenoid adduction in five patients and
      intracordal injection in two patients, was performed with success. CONCLUSIONS:
      Our results indicate that surgery for TAA is associated with a relatively high
      incidence of VCP. VCP occurred despite preservation of the recurrent laryngeal
      nerve, and the paralysis did not show a spontaneous recovery even 6 months after
      surgery.

PMID- 12065357
TI  - Multilevel likelihood ratios for identifying exudative pleural effusions(*).
AB  - STUDY OBJECTIVES: To determine multilevel likelihood ratios for pleural fluid
      tests that are commonly used to discriminate between exudative and transudative
      pleural effusions. DESIGN: Meta-analysis of patient-level data. PATIENT DATA:
      Selected studies included patients with diagnoses of exudative or transudative
      pleural effusions who underwent thoracentesis and laboratory analysis of their
      pleural fluid. MEASUREMENTS AND METHODS: Studies were identified by searching
      MEDLINE and related bibliographies. Data were obtained for 1,448 patients from
      seven primary investigators or extracted from dot plots in published reports.
      Likelihood ratios were calculated from extracted data stratified across ranges of
      test result values. RESULTS: Sufficient data were available to calculate
      multilevel likelihood ratios for the elements of Light's criteria (pleural fluid
      lactate dehydrogenase [LDH], ratio of pleural fluid to serum LDH, and ratio of
      pleural fluid to serum protein), pleural fluid protein, ratio of pleural fluid to
      serum cholesterol, pleural fluid cholesterol, and gradient of pleural fluid to
      serum albumin. Each of these tests provided levels of likelihood ratios through
      the most clinically relevant range (0 to 10). CONCLUSION: Multilevel likelihood
      ratios combined with a clinician's estimation of the pretest probability of an
      exudative effusion improve the diagnostic accuracy of discriminating between
      exudative and transudative pleural effusions. Likelihood ratios avoid the use of
      confusing terms, such as "pseudoexudates," that derive from the use of single
      cutoff points for pleural fluid tests.

PMID- 12065358
TI  - Intrapleural infusion of activated macrophages and gamma-interferon in malignant
      pleural mesothelioma: a phase II study.
AB  - STUDY OBJECTIVES: Intrapleural immunotherapy has shown some activity in patients
      with malignant mesothelioma. We conducted a multicentric pilot phase II study to
      evaluate the tolerance and the activity of intrapleurally infused autologous
      human activated macrophages (AM Phi) in patients with stage IA, IB, and IIA
      malignant pleural mesothelioma (MPM). DESIGN: AM Phi derived from in vitro
      monocyte culture were infused into the pleura of patients every week for 8
      consecutive weeks. Each infusion was followed 3 days later by an intrapleural
      injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to
      prolong the in vivo activation of infused AM Phi. Response was assessed by CT
      scan and thoracoscopy when possible. If the patient's disease progressed after AM
      Phi treatment, an additional treatment was left to the choice of the
      investigator. PATIENTS: Nineteen patients with histologically proven stage IA,
      IB, or IIA MPM were enrolled. Two patients were excluded before any AM Phi
      infusion because of complications impeding infusion. Seventeen patients were
      actually treated. After completion of the AM Phi cellular therapy, 10 patients
      were treated with chemotherapy as their diseases progressed. RESULTS: The overall
      response rate of patients actually treated was 14%. When including the two
      patients enrolled but not treated, the overall response "in intention to treat"
      was 11%; two patients had a partial response, with a duration of response of 30
      months and 3 months, respectively. One patient, who could not be evaluated by
      thoracoscopy because of pleural symphysis, is still alive without any clinical or
      radiologic sign of disease 69 months after treatment. No major adverse effects
      were observed during the infusion of either AM Phi or gamma-IFN, and there was no
      interruption of treatment because of toxicity. However, symphysis was observed in
      7 of 14 patients who received the complete treatment. The median survival of
      patients actually treated, including those who received chemotherapy after AM
      Phi, was 29.2 months. CONCLUSION: Combined infusion of AM Phi and gamma-IFN was
      well tolerated in patients with MPM; however, it had limited antitumor activity.

PMID- 12065359
TI  - Association between plasma endothelin-1 levels and Cheyne-Stokes respiration in
      patients with congestive heart failure.
AB  - STUDY OBJECTIVES: Elevated plasma endothelin-1 (ET-1) levels have been reported
      in association with hypoxia and congestive heart failure (CHF). Furthermore,
      Cheyne-Stokes respiration-central sleep apnea (CSR-CSA) has been found to
      correlate with the degree of pulmonary hypertension and the severity of CHF;
      however, the association between ET-1 levels and CSR-CSA has not been
      investigated previously. SETTING: Veterans Affairs Medical Center. INTERVENTIONS:
      We studied 46 consecutive patients with CHF (left ventricular function < or =
      40%) who underwent right-heart catheterization and overnight polysomnography.
      Thirty-nine patients completed the study. Sixteen patients (41%) had CSR-CSA, 5
      patients (13%) had obstructive apnea, and 18 patients (46%) had no sleep
      disordered breathing. Circulating plasma ET-1 levels were assayed in patients
      with CSR-CSA and in patients with no sleep-disordered breathing using
      commercially available enzyme-linked immunosorbent assay kits. RESULTS: ET-1
      levels were significantly elevated in patients with CSR-CSA (mean +/- SD, 5.4 +/-
      1.3 pg/mL) compared to those without central apnea (3.9 +/- 1.1 pg/mL; p < 0.01),
      and correlated with mean pulmonary artery pressure (r = 0.66, p < 0.01),
      pulmonary capillary wedge pressure (r = 0.56, p < 0.03), and central apnea
      frequency (r = 0.66, p < 0.01). In multivariate analysis, the severity of CSR-CSA
      was the only variable independently associated with plasma ET-1. CONCLUSIONS: We
      conclude that elevated plasma ET-1 levels are linked to the severity of CSR-CSA.
      Whether ET-1 represents an important pathogenic factor in CSR-CSA or marker of
      its occurrence requires further evaluation.

PMID- 12065360
TI  - Value of Doppler index combining systolic and diastolic myocardial performance in
      predicting cardiopulmonary exercise capacity in patients with congestive heart
      failure: effects of dobutamine.
AB  - STUDY OBJECTIVE: Doppler-derived myocardial performance index (MPI), a measure of
      combined systolic and diastolic myocardial performance, was assessed at rest and
      after low-dose dobutamine administration in patients with idiopathic or ischemic
      dilated cardiomyopathy. MPI also was correlated with other conventional
      echocardiographic indexes of left ventricular (LV) function, and its ability to
      assess cardiopulmonary exercise capacity in those patients was investigated.
      SETTINGS: A tertiary-care, university heart failure clinic. PATIENTS: Forty-two
      consecutive patients (27 men; mean [+/- SD] age, 57 +/- 10 years) with heart
      failure (New York Heart Association [NYHA] class, II to IV) who had received
      echocardiographic diagnoses of dilated cardiomyopathy. Coronary angiography
      distinguished the cause of dilated cardiomyopathy. INTERVENTIONS: Low-dose IV
      dobutamine was infused after patients underwent a baseline echocardiographic
      study. All patients also underwent a cardiopulmonary exercise test using a
      modified Naughton protocol. RESULTS: Advanced NYHA class and restrictive LV
      filling pattern were associated with higher index values. A negative correlation
      was found between MPI and LV stroke volume, cardiac output, early filling/late
      filling velocity ratio, and late LV filling velocity, as well as oxygen uptake at
      peak exercise (r = -0.550; p < 0.001) and at the anaerobic threshold (r = -0.490;
      p = 0.002). Dobutamine administration produced an improvement in MPI, reducing
      its value and decreasing the isovolumic relaxation and contraction times.
      Stepwise regression analysis revealed that the rest index and the late LV filling
      velocity were the only independent predictors of cardiopulmonary exercise
      capacity. CONCLUSION: MPI correlates inversely with LV performance, reflects
      disease severity, and is a useful complimentary variable in the assessment of
      cardiopulmonary exercise performance in patients with heart failure.

PMID- 12065361
TI  - Characteristics of the acute rise of atrial natriuretic factor during ventricular
      pacing.
AB  - BACKGROUND: Previous studies have shown that peripheral venous levels of atrial
      natriuretic factor (ANF) are elevated during ventricular pacing as a result of
      asynchrony of atrial and ventricular contraction. However, the pattern by which
      ANF rises following institution of ventricular pacing has not been fully
      established and its physiologic consequences are unclear. METHODS: Eight
      ambulatory patients in stable condition with dual-chamber pacemakers were
      studied. The pacemaker was reprogrammed from the dual-chamber to the ventricular
      pacing mode for 3 h, during which serial measurements were made of BP, heart rate
      and rhythm, levels of ANF, and plasma renin activity (PRA). RESULTS: ANF levels
      rose markedly but slowly following the onset of ventricular pacing, reaching
      levels as high as 694% of control. The rise occurred over the course of 120 min,
      at which time the average value for the group plateaued at 82.5 +/- 22.1 fmol/mL
      (mean +/- SEM) vs 25.3 +/- 4.5 fmol/mL at control (p < 0.01); there was, however,
      marked variability in individual responses. By contrast, levels of PRA remained
      remarkably stable. Average BP changes were small, although there was a trend in
      the later part of the study for systolic pressure to decrease. CONCLUSIONS: ANF
      levels rise markedly but gradually after institution of ventricular pacing and,
      hence, acute pacing studies must account for this delay in their design. The
      physiologic importance of the rise in ANF should be evaluated further since the
      rise in peptide levels may be associated with a decrease in systolic BP.

PMID- 12065362
TI  - Variations in the measurement of weaning parameters: a survey of respiratory
      therapists.
AB  - OBJECTIVES: Respiratory therapists differ in the methods used to obtain weaning
      parameters. A questionnaire survey was conducted to better characterize those
      differences. DESIGN: A questionnaire survey was conducted among respiratory
      therapists from nine hospitals in the Los Angeles area. The four-page, 32
      question instrument was self-administered and anonymous. Responses were tabulated
      for analysis. SETTING: Respondents from nine hospitals, three hospitals with
      residency training programs and six community hospitals without training programs
      in the Los Angeles area. PARTICIPANTS: One hundred two respiratory therapists.
      RESULTS: There was no universally acknowledged group of weaning parameters,
      although four parameters were named by > 90%. There was wide variation in methods
      used to obtaining weaning parameters. Almost all (91%) obtained measurements with
      the patients breathing their current fraction of inspired oxygen, but there was
      great variability in the ventilator mode used to collect these parameters (T
      tube, continuous positive airway pressure, pressure support), with an equally
      wide range of pressures added to each mode (0 to 10 cm H(2)O). There was great
      variation in the time (< 1 to > 15 min) before recording weaning parameters.
      Measurement of parameters was done either with bedside instruments or read from
      the ventilator display. The maximal inspiratory pressure had great variation in
      the duration of airway occlusion (< 1 to 20 s), with the most frequent time frame
      being 2 to 4 s. Differences were noted between therapists from the same hospital
      as well as between hospitals. CONCLUSIONS: There is great variation among
      respiratory therapists when obtaining weaning parameters. This calls for further
      standardization of the measurement of weaning parameters.

PMID- 12065363
TI  - Effect of crystalloid resuscitation and inhalation injury on extravascular lung
      water: clinical implications.
AB  - STUDY OBJECTIVE: Arterial thermal dilution with an integrated fiberoptic
      monitoring system (COLD Z-021; Pulsion Medical Systems; Munich, Germany) allows
      measurement of extravascular lung water (EVLW) and pulmonary permeability index
      (PPI). The aim of this study was to evaluate the widespread clinical assumption
      that early respiratory failure following burn and inhalation injury is due to
      interstitial fluid accumulation in the lung. DESIGN: Clinical, prospective study.
      SETTING: ICU of a university referral center of burn care. PATIENTS: Thirty-five
      severely burned adults (> 20% of body surface area). INTERVENTIONS: Resuscitation
      therapy was guided by the results of hemodynamic monitoring using the
      intrathoracic blood volume (ITBV) as a cardiac preload indicator. The
      resuscitation goals included a normalization of preload (ITBV > 850 mL/m(2)) and
      cardiac index (> 3.5 L/min/m(2)) within 24 h after ICU admission. Fluid loading
      was implemented to reach these goals. MEASUREMENTS AND RESULTS: One hundred forty
      lung water measurements were performed at 0 h, 12 h, 24 h, and 48 h after
      admission to the ICU. Significant elevation of EVLW and PPI was found in three
      measurements (2%) at 48 h after ICU admission, and was in one patient associated
      with inhalation injury. EVLW and PPI were not significantly different between
      patients with and without inhalation injury. No correlation was found between
      resuscitation volume and EVLW (r(2) = 0.02) or between the alveolar-arterial
      oxygen pressure difference and EVLW (r(2) = 0.017). Chest radiograph
      abnormalities were found in 2 of 22 patients with inhalation injury; these were
      not associated with increased values of EVLW. CONCLUSION: Early fluid
      accumulation in the lung in burned patients is very uncommon, even in the
      presence of inhalation injury. There is no evidence that thermal injury causes an
      increase in pulmonary capillary membrane permeability.

PMID- 12065364
TI  - Does acute organ dysfunction predict patient-centered outcomes?
AB  - BACKGROUND: Long-term patient-centered outcomes after acute illness may be
      associated with baseline health status, the development of acute organ
      dysfunction (AOD), or both. STUDY OBJECTIVE: To determine whether AOD (occurring
      in the first 30 days) was independently associated with 90-day survival,
      functional status, and health-related quality of life (HRQL) after controlling
      for baseline health status in patients who were hospitalized with community
      acquired pneumonia (CAP) and survived to day 30. DESIGN: Prospective
      observational study. SETTING: Four hospitals in Pennsylvania, Massachusetts, and
      Nova Scotia, Canada, between October 1991 and March 1994. PATIENTS: One thousand
      three hundred thirty-nine patients who were hospitalized with CAP. INTERVENTIONS:
      Baseline and 90-day quality-of-life and functional status questionnaires.
      MEASUREMENTS AND RESULTS: We determined the 90-day survival rate in all patients
      (n = 1,339) and the functional status and HRQL in subsets of 261 and 219
      patients, respectively. AOD occurred in one or more organ system in 639 patients
      (47.7%) and in two or more organ systems in 255 patients (19.1%). In univariate
      analyses, greater AOD was associated with a higher mortality rate (p < 0.0001), a
      lower HRQL (p = 0.006), and lower functional status (p = 0.009) at 90 days.
      However, after adjusting for baseline HRQL, AOD was not associated with mortality
      (p = 0.47) or HRQL (p = 0.14) at 90 days and was only weakly associated with 90
      day functional status (p = 0.02). CONCLUSIONS: Although patients who develop AOD
      are at risk for late adverse outcomes, their risk is due predominantly to poor
      baseline status prior to illness and not to the organ dysfunction per se.
      Therefore, AOD does not appear to have significant long-term ramifications for
      patient-centered outcomes.

PMID- 12065365
TI  - Incidence of ARDS in an adult population of northeast Ohio.
AB  - STUDY OBJECTIVES: To assess the incidence of the ARDS in a well-defined adult
      population. DESIGN: Kaiser Permanente of northeast Ohio, a health maintenance
      organization, uses the Cleveland Clinic Foundation as its only tertiary care
      center. In an ongoing prospective assessment in the Cleveland Clinic ICUs, we
      identified adult Kaiser Permanente patients with ARDS between 1996 and 1999. ARDS
      was defined according to the 1994 American-European Consensus Conference
      criteria. The denominator in the incidence calculation was the adult members of
      Kaiser Permanente of each year of the study period, and the numerator was the new
      adult ARDS patients in this particular year. The cause of ARDS, the mortality,
      and the cause of death were retrospectively identified, as well as other
      characteristics of the study population. RESULTS: ARDS was diagnosed in 66
      patients during the 3-year study period. The incidence per 100,000 population was
      11.4 in 1996, 19.8 in 1997, and 14.4 in 1998; the overall incidence was
      15.3/100,000/yr. The mean PaO(2)/fraction of inspired oxygen (+/- SD) was 110.8
      +/- 37.8, the mean APACHE II was 23.4 +/- 6.9, and the mean ICU stay was 12.0 +/-
      9.5 days. The most common cause of ARDS was direct lung injury (75.8%), and the
      most common cause of death was septic shock (53.8%). CONCLUSION: The incidence of
      ARDS in an adult population in northeast Ohio was 15.3/100,000/yr, a number that
      is slightly higher but comparable to recent estimates reported by other
      researchers.

PMID- 12065366
TI  - The role of anticholinergics in acute asthma treatment: an evidence-based
      evaluation.
AB  - The role for anticholinergic medications in acute asthma is not well-defined.
      Thus, the use of therapy with anticholinergics and beta(2)-agonists, either
      simultaneously or in sequence, has produced positive as well as negative results
      in trials. Therefore, the current recommendations for the use of these drugs in
      the emergency department (ED) and hospital management of asthma exacerbations are
      not precise. This review answers the following question: what level of evidence
      is available in the literature to support the use of anticholinergic medications
      in combination with beta(2)-agonists in acute asthma patients? We limited the
      search on our therapy question to systematic reviews of randomized trials and/or
      randomized controlled trials not included in the reviews. After an extensive
      review of the most relevant evidence, the following conclusions may be
      emphasized. (1) The use of multiple doses of ipratropium bromide are indicated in
      the ED treatment of children and adults with severe acute asthma. The studies
      reported a substantial reduction in hospital admissions (30 to 60%; number needed
      to treat, 5 to 11) and significant differences in lung function favoring the
      combined treatment. No apparent increase in the occurrence of side effects was
      observed. (2) The use of single-dose protocols of ipratropium bromide with
      beta(2)-agonist treatment produced, particularly in children with more severe
      acute asthma, a modest improvement in pulmonary function without reduction in
      hospital admissions; in adults, the data showed a similar increase in pulmonary
      function with an approximately 35% reduction in the hospital admission rate. In
      patients with mild-to-moderate acute asthma, there is no apparent benefit from
      adding a single dose of an anticholinergic medication.

PMID- 12065367
TI  - The clinical spectrum of pulmonary aspergillosis.
AB  - Aspergillus is a ubiquitous fungus that causes a variety of clinical syndromes in
      the lung, ranging from aspergilloma in patients with lung cavities, to chronic
      necrotizing aspergillosis in those who are mildly immunocompromised or have
      chronic lung disease. Invasive pulmonary aspergillosis (IPA) is a severe and
      commonly fatal disease that is seen in immunocompromised patients, while allergic
      bronchopulmonary aspergillosis is a hypersensitivity reaction to Aspergillus
      antigens that mainly affects patients with asthma. In light of the increasing
      risk factors leading to IPA, such as organ transplantation and immunosuppressive
      therapy, and recent advances in the diagnosis and treatment of Aspergillus
      related lung diseases, it is essential for clinicians to be familiar with the
      clinical presentation, diagnostic methods, and approach to management of the
      spectrum of pulmonary aspergillosis.

PMID- 12065368
TI  - Predicting fluid responsiveness in ICU patients: a critical analysis of the
      evidence.
AB  - STUDY OBJECTIVE: To identify and critically review the published peer-reviewed,
      English-language studies investigating predictive factors of fluid responsiveness
      in ICU patients. DESIGN: Studies were collected by doing a search in MEDLINE
      (from 1966) and scanning the reference lists of the articles. Studies were
      selected according to the following criteria: volume expansion performed in
      critically ill patients, patients classified in two groups (responders and
      nonresponders) according to the effects of volume expansion on stroke volume or
      on cardiac output, and comparison of responder and nonresponder patients'
      characteristics before volume expansion. RESULTS: Twelve studies were analyzed in
      which the parameters tested were as follows: (1) static indicators of cardiac
      preload (right atrial pressure [RAP], pulmonary artery occlusion pressure [PAOP],
      right ventricular end-diastolic volume [RVEDV], and left ventricular end
      diastolic area [LVEDA]); and (2) dynamic parameters (inspiratory decrease in RAP
      [Delta RAP], expiratory decrease in arterial systolic pressure [Delta down],
      respiratory changes in pulse pressure [Delta PP], and respiratory changes in
      aortic blood velocity [Delta Vpeak]). Before fluid infusion, RAP, PAOP, RVEDV,
      and LVEDA were not significantly lower in responders than in nonresponders in
      three of five studies, in seven of nine studies, in four of six studies, and in
      one of three studies, respectively. When a significant difference was found, no
      threshold value could discriminate responders and nonresponders. Before fluid
      infusion, Delta RAP, Delta down, Delta PP, and Delta Vpeak were significantly
      higher in responders, and a threshold value predicted fluid responsiveness with
      high positive (77 to 95%) and negative (81 to 100%) predictive values.
      CONCLUSION: Dynamic parameters should be used preferentially to static parameters
      to predict fluid responsiveness in ICU patients.

PMID- 12065369
TI  - Pulmonary artery catheter: does the problem lie in the users?
AB  - The aims of this study were to look for the variability in the treatment of
      circulatory shock and to assess the extent to which this variability was reduced
      by pulmonary artery catheterization (PAC). At three international conferences in
      1997-1998 (European Society of Critical Care Medicine, French Language Society
      for Critical Care [Societe de Reanimation de Langue Francaise], and Society of
      Critical Care Medicine), a real-life clinical case was discussed in meetings
      among physicians and a panel of experts, with assistance from an expert computer
      program. A total of 417 physicians took part in the discussions. Following the
      clinical presentation, only 38% of physicians suggested the same treatment as the
      experts, and 35% suggested potentially harmful treatments. Complete hemodynamic
      data from PAC significantly decreased the range of suggested treatments, improved
      agreement among physicians themselves as well as the agreement between physicians
      and experts, and decreased the number of potentially harmful propositions.
      However, whereas almost 80% of participants finally agreed on the treatment after
      one to three invasive hemodynamic sets of measurements, at least 10% persisted in
      suggesting potentially harmful treatments. PAC improved interphysician agreement,
      but our data suggest that yet greater agreement could be achieved by improving
      the theoretical training of practitioners.

PMID- 12065370
TI  - Sexual content of advertisements and the smoking process in adolescents.
AB  - STUDY OBJECTIVE: s: To analyze the perception of sexual content (PSC) of tobacco
      advertisements and its potential impact on the process of smoking in adolescents.
      DESIGN, PARTICIPANTS, AND SETTING: A questionnaire was administered to 1,186
      adolescents at the National Institute of Respiratory Diseases in Mexico City to
      determine the PSC. In addition, age, gender, susceptibility, receptivity,
      parental smoking and education, anxiety, depressive symptoms, school category,
      and grade were determined. INTERVENTIONS AND MEASUREMENTS: The images of two
      advertisements were projected in color onto a screen. One of the images had
      unquestionable sexual content. The impact of the images was evaluated at the same
      time in the questionnaire. RESULTS: Forty-one percent of participants were
      nonsmokers (25% nonsusceptible and 16% susceptible), whereas 59% were smokers
      (47% experimenters and 12% established). Sixty-six percent were receptive to
      promotions of the tobacco companies. Seventy-two percent perceived sexual
      contents in the advertisements. A logistic regression model showed that
      receptivity (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3 to 3.4),
      minimal PSC (OR, 2.6; 95% CI, 1.7 to 4.0), and high PSC (OR, 4.4; 95% CI, 2.4 to
      8.0) were significantly associated with the status of smokers, whether
      experimenters or established. The strongest association was found with
      established smokers. Further analysis showed that male gender was significantly
      associated with high levels of PSC. CONCLUSIONS: These results show that a high
      percentage of adolescents perceived sexual content in the tobacco advertisement,
      which, independent of the subject's receptivity, plays a role in the process of
      smoking, especially in male adolescents.

PMID- 12065371
TI  - The potentially coercive nature of some clinical research trial acronyms.
AB  - STUDY OBJECTIVES: To evaluate the potential coerciveness of clinical research
      trial (CRT) acronyms, and to make clinicians aware that some CRT acronyms may be
      coercive to research subjects by subliminally enticing or outwardly promising
      something that the CRT may not be able to deliver. DESIGN: Analysis of CRT
      acronyms for pleasantness and meaningfulness as assessed by studies in the
      behavioral and social psychology literature. RESULTS: Of 2,383 acronyms for CRTs
      analyzed, 155 acronyms (6.5%) were assessed as possibly, probably, or almost
      certainly coercive. On a Likert scale from 1 to 5 for pleasantness or
      meaningfulness, the acronyms identified as almost certainly coercive had a mean
      pleasantness score of 4.21 (range, 3.70 to 4.57), the acronyms identified as
      probably coercive had a mean score of 3.79 (range, 2.45 to 5.00), and the
      acronyms identified as possibly coercive had a mean score of 3.89 (range, 2.81 to
      5.00). CONCLUSIONS: A distraught or frightened patient with a life-threatening
      illness who is offered a research study with an acronym of CURE, HOPE, HELP,
      IMPROVED, LIFE, RESCUE, MIRACL (sic), SAVED, or ALIVE is possibly being coerced
      by the acronym. Institutional review boards (IRBs) and the medical research
      community would not tolerate a CRT entitled, "A Surefire Cure for Cancer." They
      should be no more tolerant of a CRT with an acronym listed above. It is time for
      researchers, sponsors, and IRBs to take a more responsible approach to
      potentially coercive CRT acronyms and discourage or prohibit their use.

PMID- 12065372
TI  - Donor criteria in lung transplantation: an issue revisited.
AB  - The availability of suitable lung donors is the major limitation to increasing
      the number of lung transplants performed. Donor criteria developed early in the
      lung transplant era have not been rigorously evaluated. Each of the "standard"
      lung donor criteria currently in use should be challenged by obtaining,
      analyzing, and using multicenter data from a well-designed database. Only in this
      way will our understanding of appropriate lung donor criteria advance and the
      pool of lungs available for transplantation increase.

PMID- 12065373
TI  - Four-step local anesthesia and sedation for thoracoscopic diagnosis and
      management of pleural diseases.
AB  - STUDY OBJECTIVES: Most thoracic surgeons perform thoracoscopy under general
      anesthesia using a double-lumen endotracheal tube. We describe our own technique
      for performing thoracoscopy under local anesthesia and sedation. DESIGN, SETTING,
      PATIENTS: Forty-five patients underwent the procedure under local anesthesia and
      sedation (mean age, 64 years; age range, 40 to 92 years). A known history of
      cancer was present in 12 patients. American Society of Anesthesiology score was I
      in 1 patient, II in 16 patients, III in 22 patients, IV in 5 patients, and V in 1
      patient. Premedication was comprised of droperidol, 5 mg, and atropine, 0.5 mg,
      administered 20 min before the scheduled operating room time. Sedation was
      maintained by diazepam injection, 3 mg. Four-step local anesthesia in the planned
      intercostal space using 10 mL of ropivacaine, 7.5 mg/mL, was performed. RESULTS:
      Mean operative time was 45.7 min (range, 20 to 90 min); mean time of anesthesia
      was 71.3 min (range, 30 to 150 min). Among patients with pleural effusion, 23
      effusions were simple and 16 effusions were complex. Talc was administrated in 28
      patients. Complications were intraoperative bleeding (one patient), hyperpyrexia
      (eight patients), and atrial fibrillation (two patients). The mean time for
      removal of the chest drain was 5.6 days (range, 2 to 13 days). Postoperative
      hospital stay was 6.4 days (range, 2 to 14 days). No hospital mortality occurred.
      Follow-up is complete in all patients (mean, 92.8 days; range, 31 to 270 days).
      CONCLUSION: Four-step local anesthesia and sedation is a simple and effective
      method of performing a video-assisted thoracic procedure to diagnose and treat
      simple thoracic pathologies.

PMID- 12065374
TI  - Acute-onset quadriplegia, respiratory failure, and ventricular tachycardia in a
      21-year-old man following a soccer match.

PMID- 12065375
TI  - Seasonal dyspnea.

PMID- 12065377
TI  - Spirometric abnormalities associated with chronic bronchitis, asthma, and airway
      hyperresponsiveness among boilermaker construction workers.
AB  - STUDY OBJECTIVES: In a 2-year longitudinal study of boilermaker construction
      workers, we found a significant association between working at oil-fired, coal
      fired, and gas-fired industries during the past year and reduced lung function.
      In the present study, we investigated whether chronic bronchitis, asthma, or
      baseline methacholine airway responsiveness can explain the heterogeneity in lung
      function response to boilermaker work. DESIGN: This study is part of an ongoing
      prospective cohort study of boilermakers. Exposure was assessed with a work
      history questionnaire. Spirometry was performed annually to assess lung function.
      A generalized estimating equation approach was used to account for the repeated
      measures design. SETTING: Boilermaker union members. PARTICIPANTS: One hundred
      eighteen boilermakers participated in the study. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Self-reported history of chronic bronchitis and asthma
      were associated with a larger FEV1 reduction in response to workplace exposure at
      coal-fired and gas-fired industries. Although we found a high prevalence (39%) of
      airway hyperresponsiveness (provocative concentration of methacholine causing a
      20% fall in FEV1 of < 8 mg/mL) among boilermakers, we did not find a consistent
      pattern of effect modification by airway responsiveness. CONCLUSIONS: Although
      chronic bronchitis and asthma were associated with a greater loss in lung
      function in response to hours worked as a boilermaker, and therefore they acted
      as effect modifiers of the exposure-lung function relationship, airway
      hyperresponsiveness did not. However, the high prevalence of airway
      hyperresponsiveness found in the cohort may be a primary consequence of long-term
      workplace exposure among boilermakers.

PMID- 12065376
TI  - A longitudinal study of chest radiographic changes of workers in the refractory
      ceramic fiber industry.
AB  - STUDY OBJECTIVE: This industry-wide longitudinal study examines chest
      radiographic changes of workers manufacturing refractory ceramic fibers (RCF).
      DESIGN: Chest radiographs were obtained every 3 years and were interpreted using
      the 1980 International Labour Organization classification for pneumoconiosis.
      Three exposure metrics were calculated: duration and latency in a production job,
      and cumulative exposure (fiber-months per cubic centimeter). PARTICIPANTS: The
      radiographic survey included 625 current workers at five manufacturing sites and
      383 former workers at two of the five sites. MEASUREMENTS AND RESULTS: Pleural
      changes were seen in 27 workers (2.7%). Of workers with > 20 years of latency
      from initial production job or 20 years of duration in a production job, 16
      workers (8.0%) and 5 workers (8.1%) demonstrated pleural changes, respectively.
      Results from the cumulative exposure analysis (> 135 fiber-months per cubic
      centimeter) demonstrated a significant elevated odds ratio (OR) of 6.0 (95%
      confidence interval [CI], 1.4 to 31.0). The incidence of irregular opacities at
      profusion categories > or = 1/0 was similar to other nonspecified dust-exposed
      worker populations at 1.0%, and showed a nonsignificant elevated OR in regard to
      cumulative fiber exposure of 4.7 (95% CI, 0.97 to 23.5). CONCLUSIONS: RCF are
      significantly associated with pleural changes that were predominantly pleural
      plaques, but have not resulted in a statistically significant increase in
      interstitial changes.

PMID- 12065378
TI  - Thymoma and myotonic dystrophy: successful treatment with chemotherapy and
      radiation: case report and review of the literature.
AB  - We present the case of a 42-year-old woman with myotonic dystrophy and thymoma.
      She was treated with combination chemotherapy followed by external beam
      radiation, and remains in remission 19 months after thymoma was diagnosed. The
      myotonic dystrophy is unchanged. Only six cases of this nature have been reported
      in the literature, and this patient is the first to be successfully treated with
      combined modality therapy.

PMID- 12065379
TI  - Anomalous collateral from the coronary artery to the affected lung in a case of
      congenital absence of the left pulmonary artery: effect on coronary circulation.
AB  - A case of congenital absence of the left pulmonary artery, in which perfusion of
      the affected lung was accomplished via an arterial shunt from the circumflex
      coronary artery, is discussed. Data from myocardial perfusion scintigraphy showed
      that myocardial perfusion was unaffected by the existence of the shunt, largely
      because the flow through the shunt occurred mainly during systole.

PMID- 12065380
TI  - New procedure: bronchoscopic endobronchial sealing; a new mode of managing
      hemoptysis.
AB  - Six patients with hemoptysis were treated by endobronchial sealing, with n-butyl
      cyanoacrylate, of the bleeding segment or subsegment. There was an immediate
      arrest of bleeding without any recurrence for a mean follow-up period of 127 (+/-
      67.17) days. Endobronchial sealing appears to be an effective method of managing
      hemoptysis.

PMID- 12065381
TI  - Endobronchial actinomycosis associated with foreign body: four cases and a review
      of the literature.
AB  - Four cases of primary endobronchial actinomycosis associated with an inhaled
      foreign body are described. In the light of these cases and those previously
      reported in the literature, we describe the main features of this uncommon
      association. All patients were > 55 years old, were predominantly men, and were
      usually in a debilitated state. In > 50% of cases, the clinical presentation was
      suggestive of lung cancer. Thoracic CT rarely revealed a foreign body, but the
      granulomatous reaction of the bronchial wall was sometimes suggestive of
      bronchial thickening. Sulfur granules identified on bronchial biopsies were
      highly suggestive of actinomycosis in most cases, but microbiological culture
      findings were usually negative. Antibiotics generally ensure good recovery.
      Extraction of the foreign body was delayed after antibiotic therapy in one half
      of cases, suggesting the need for endoscopic follow-up in bronchial
      actinomycosis.

PMID- 12065382
TI  - Progression of idiopathic pulmonary fibrosis in native lungs after single lung
      transplantation.
AB  - This retrospective, single-center study was conducted to assess the response of
      native idiopathic pulmonary fibrosis (IPF) lungs to a potent cyclosporine-based
      immunosuppressive regimen in single-lung transplantation recipients. The study
      included IPF patients who had undergone single-lung transplantation and had chest
      CT scans before and after transplantation. Five patients underwent single-lung
      transplantation for IPF between April 1992 and January 2001, and met entry
      criteria. All patients were placed on an immunosuppressive regimen consisting of
      prednisone, azathioprine, and cyclosporine. In two of the five patients, ground
      glass attenuation in the native IPF lung improved post-transplantation. However,
      fibrotic changes progressed in all five patients. In patients with advanced IPF,
      a potent cyclosporine-based immunosuppressive regimen is not likely to have an
      effect on the progression of the disease.

PMID- 12065384
TI  - Critically ill obstetric patients treated in an ICU.

PMID- 12065385
TI  - Octreotide in the treatment of chylothorax.

PMID- 12065386
TI  - Strength of evidence for low-molecular-weight heparin.

PMID- 12065388
TI  - Preoperative bronchoscopic biopsies and staging.

PMID- 12065389
TI  - Endobronchial sarcoidosis and hyperreactive airways disease.

PMID- 12065390
TI  - Outpatient pulmonary rehabilitation.

PMID- 12065391
TI  - Salmeterol powder provides significantly better benefit than montelukast in
      asthmatic patients receiving concomitant inhaled corticosteroid therapy.

PMID- 12065392
TI  - Spiral CT is not the final answer.

PMID- 12065393
TI  - Workup following tissue expectoration.

PMID- 12065394
TI  - Environmental tobacco smoke exposure and adult asthma.

PMID- 12065395
TI  - Worry list.

PMID- 12065398
TI  - Structural basis for the interaction between NTF2 and nucleoporin FxFG repeats.
AB  - Interactions with nucleoporins containing FxFG-repeat cores are crucial for the
      nuclear import of RanGDP mediated by nuclear transport factor 2 (NTF2). We
      describe here the 1.9 A resolution crystal structure of yeast NTF2-N77Y bound to
      a FxFG-nucleoporin core, which provides a basis for understanding this
      interaction and its role in nuclear trafficking. The two identical FxFG binding
      sites on the dimeric molecule are formed by residues from each chain of NTF2.
      Engineered mutants at the interaction interface reduce the binding of NTF2 to
      nuclear pores and cause reduced growth rates and Ran mislocalization when
      substituted for the wild-type protein in yeast. Comparison with the crystal
      structure of FG-nucleoporin cores bound to importin-beta and TAP/p15 identified a
      number of common features of their binding sites. The structure of the binding
      interfaces on these transport factors provides a rationale for the specificity of
      their interactions with nucleoporins that, combined with their weak binding
      constants, facilitates rapid translocation through NPCs during nuclear
      trafficking.

PMID- 12065399
TI  - Crystal structure of the Lactococcus lactis formamidopyrimidine-DNA glycosylase
      bound to an abasic site analogue-containing DNA.
AB  - The formamidopyrimidine-DNA glycosylase (Fpg, MutM) is a bifunctional base
      excision repair enzyme (DNA glycosylase/AP lyase) that removes a wide range of
      oxidized purines, such as 8-oxoguanine and imidazole ring-opened purines, from
      oxidatively damaged DNA. The structure of a non-covalent complex between the
      Lactoccocus lactis Fpg and a 1,3-propanediol (Pr) abasic site analogue-containing
      DNA has been solved. Through an asymmetric interaction along the damaged strand
      and the intercalation of the triad (M75/R109/F111), Fpg pushes out the Pr site
      from the DNA double helix, recognizing the cytosine opposite the lesion and
      inducing a 60 degrees bend of the DNA. The specific recognition of this cytosine
      provides some structural basis for understanding the divergence between Fpg and
      its structural homologue endo nuclease VIII towards their substrate
      specificities. In addition, the modelling of the 8-oxoguanine residue allows us
      to define an enzyme pocket that may accommodate the extrahelical oxidized base.

PMID- 12065400
TI  - Plasticity in protein-DNA recognition: lac repressor interacts with its natural
      operator 01 through alternative conformations of its DNA-binding domain.
AB  - The lac repressor-operator system is a model system for understanding protein-DNA
      interactions and allosteric mechanisms in gene regulation. Despite the wealth of
      biochemical data provided by extensive mutations of both repressor and operator,
      the specific recognition mechanism of the natural lac operators by lac repressor
      has remained elusive. Here we present the first high-resolution structure of a
      dimer of the DNA-binding domain of lac repressor bound to its natural operator
      01. The global positioning of the dimer on the operator is dramatically
      asymmetric, which results in a different pattern of specific contacts between the
      two sites. Specific recognition is accomplished by a combination of elongation
      and twist by 48 degrees of the right lac subunit relative to the left one,
      significant rearrangement of many side chains as well as sequence-dependent
      deformability of the DNA. The set of recognition mechanisms involved in the lac
      repressor-operator system is unique among other protein-DNA complexes and
      presents a nice example of the adaptability that both proteins and DNA exhibit in
      the context of their mutual interaction.

PMID- 12065401
TI  - Crystal structure of auxin-binding protein 1 in complex with auxin.
AB  - The structure of auxin-binding protein 1 (ABP1) from maize has been determined at
      1.9 A resolution, revealing its auxin-binding site. The structure confirms that
      ABP1 belongs to the ancient and functionally diverse germin/seed storage 7S
      protein superfamily. The binding pocket of ABP1 is predominantly hydrophobic with
      a metal ion deep inside the pocket coordinated by three histidines and a
      glutamate. Auxin binds within this pocket, with its carboxylate binding the zinc
      and its aromatic ring binding hydrophobic residues including Trp151. There is a
      single disulfide between Cys2 and Cys155. No conformational rearrangement of ABP1
      was observed when auxin bound to the protein in the crystal, but examination of
      the structure reveals a possible mechanism of signal transduction.

PMID- 12065402
TI  - Crystal structure of vesicular stomatitis virus matrix protein.
AB  - The vesicular stomatitis virus (VSV) matrix protein (M) interacts with cellular
      membranes, self-associates and plays a major role in virus assembly and budding.
      We present the crystallographic structure, determined at 1.96 A resolution, of a
      soluble thermolysin resistant core of VSV M. The fold is a new fold shared by the
      other vesiculovirus matrix proteins. The structure accounts for the loss of
      stability of M temperature-sensitive mutants deficient in budding, and reveals a
      flexible loop protruding from the globular core that is important for self
      assembly. Membrane floatation shows that, together with the M lysine-rich N
      terminal peptide, a second domain of the protein is involved in membrane binding.
      Indeed, the structure reveals a hydrophobic surface located close to the
      hydrophobic loop and surrounded by conserved basic residues that may constitute
      this domain. Lastly, comparison of the negative-stranded virus matrix proteins
      with retrovirus Gag proteins suggests that the flexible link between their major
      membrane binding domain and the rest of the structure is a common feature shared
      by these proteins involved in budding and virus assembly.

PMID- 12065403
TI  - Topological changes in the transmembrane domains of hepatitis C virus envelope
      glycoproteins.
AB  - Hepatitis C virus proteins are synthesized as a polyprotein cleaved by a signal
      peptidase and viral proteases. The behaviour of internal signal sequences at the
      C-terminus of the transmembrane domains of hepatitis C virus envelope proteins E1
      and E2 is essential for the topology of downstream polypeptides. We determined
      the topology of these transmembrane domains before and after signal sequence
      cleavage by tagging E1 and E2 with epitopes and by analysing their accessibility
      in selectively permeabilized cells. We showed that, after cleavage by signal
      peptidase in the endoplasmic reticulum, the C-terminal orientation of these
      transmembrane domains changed from luminal to cytosolic. The dynamic behaviour of
      these transmembrane domains is unique and it is linked to their
      multifunctionality. By reorienting their C-terminus toward the cytosol and being
      part of a transmembrane domain, the signal sequences at the C-terminus of E1 and
      E2 contribute to new functions: (i) membrane anchoring; (ii) E1E2
      heterodimerization; and (iii) endoplasmic reticulum retention.

PMID- 12065404
TI  - The yeast prion Ure2p retains its native alpha-helical conformation upon assembly
      into protein fibrils in vitro.
AB  - The yeast inheritable phenotype [URE3] is thought to result from conformational
      changes in the normally soluble and highly helical protein Ure2p. In vitro, the
      protein spontaneously forms long, straight, insoluble protein fibrils at neutral
      pH. Here we show that fibrils of intact Ure2p assembled in vitro do not possess
      the cross beta-structure of amyloid, but instead are formed by the polymerization
      of native-like helical subunits that retain the ability to bind substrate
      analogues. We further show that dissociation of the normally dimeric protein to
      its constituent monomers is a prerequisite for assembly into fibrils. By
      analysing the nature of early assembly intermediates, as well as fully assembled
      Ure2p fibrils using atomic force microscopy, and combining the results with
      experiments that probe the fidelity of the native fold in protein fibrils, we
      present a model for fibril formation, based on assembly of native-like monomers,
      driven by interactions between the N-terminal glutamine and asparagine-rich
      region and the C-terminal functional domain. The results provide a rationale for
      the effect of mutagenesis on prion formation and new insights into the mechanism
      by which this, and possibly other inheritable factors, can be propagated.

PMID- 12065405
TI  - Control of germination and lipid mobilization by COMATOSE, the Arabidopsis
      homologue of human ALDP.
AB  - Embryo dormancy in flowering plants is an important dispersal mechanism that
      promotes survival of the seed through time. The subsequent transition to
      germination is a critical control point regulating initiation of vegetative
      growth. Here we show that the Arabidopsis COMATOSE (CTS) locus is required for
      this transition, and acts, at least in part, by profoundly affecting the
      metabolism of stored lipids. CTS encodes a peroxisomal protein of the ATP binding
      cassette (ABC) transporter class with significant identity to the human X-linked
      adrenoleukodystrophy protein (ALDP). Like X-ALD patients, cts mutant embryos and
      seedlings exhibit pleiotropic phenotypes associated with perturbation in fatty
      acid metabolism. CTS expression transiently increases shortly after imbibition
      during germination, but not in imbibed dormant seeds, and genetic analyses show
      that CTS is negatively regulated by loci that promote embryo dormancy through
      multiple independent pathways. Our results demonstrate that CTS regulates
      transport of acyl CoAs into the peroxisome, and indicate that regulation of CTS
      function is a major control point for the switch between the opposing
      developmental programmes of dormancy and germination.

PMID- 12065406
TI  - Shigella deliver an effector protein to trigger host microtubule destabilization,
      which promotes Rac1 activity and efficient bacterial internalization.
AB  - Shigella deliver a subset of effectors into the host cell via the type III
      secretion system, that stimulate host cell signal pathways to modulate the actin
      dynamics required for invasion of epithelial cells. Here we show that one of the
      Shigella effectors, called VirA, can interact with tubulin to promote microtubule
      (MT) destabilization, and elicit protrusions of membrane ruffling. Under in vitro
      conditions, VirA inhibited polymerization of tubulin and stimulated MT
      destabilization. Upon microinjection of VirA into HeLa cells, a localized
      membrane ruffling was induced rapidly. Overexpression of VirA in host cells
      caused MT destruction and protruding membrane ruffles which were absent when VirA
      was co-expressed with a dominant-negative Rac1 mutant. Indeed, Shigella but not
      the virA mutant stimulated Rac1, including the formation of membrane ruffles in
      infected cells. Importantly, the MT structure beneath the protruding ruffling was
      destroyed. Furthermore, drug-induced MT growth in HeLa cells greatly enhanced the
      Shigella entry. These results indicate that VirA is a novel type of bacterial
      effector capable of inducing membrane ruffling through the stimulation of MT
      destabilization.

PMID- 12065407
TI  - INK4a-deficient human diploid fibroblasts are resistant to RAS-induced
      senescence.
AB  - The CDKN2A tumour suppressor locus encodes two distinct proteins, p16(INK4a) and
      p14(ARF), both of which have been implicated in replicative senescence, the state
      of permanent growth arrest provoked in somatic cells by aberrant proliferative
      signals or by cumulative population doublings in culture. Here we describe
      primary fibroblasts from a member of a melanoma-prone family who is homozygous
      for an intragenic deletion in CDKN2A. Analyses of the resultant gene products
      imply that the cells are p16(INK4a) deficient but express physiologically
      relevant levels of a frameshift protein that retains the known functions of
      p14(ARF). Although they have a finite lifespan, the cells are resistant to arrest
      by oncogenic RAS. Indeed, ectopic expression of RAS and telomerase (hTERT)
      results in outgrowth of anchorage-independent colonies that have essentially
      diploid karyotypes and functional p53. We find that in human fibroblasts, ARF is
      not induced demonstrably by RAS, pointing to significant differences between the
      proliferative barriers implemented by the CDKN2A locus in different cell types or
      species.

PMID- 12065408
TI  - A balance of KIF1A-like kinesin and dynein organizes early endosomes in the
      fungus Ustilago maydis.
AB  - In Ustilago maydis, bidirectional transport of early endosomes is microtubule
      dependent and supports growth and cell separation. During early budding,
      endosomes accumulate at putative microtubule organizers within the bud, whereas
      in medium-budded cells, endosome clusters appear at the growing ends of
      microtubules at the distal cell pole. This suggests that motors of opposing
      transport direction organize endosomes in budding cells. Here we set out to
      identify these motors and elucidate the molecular mechanism of endosome
      reorganization. By PCR we isolated kin3, which encodes an UNC-104/KIF1-like
      kinesin from U.maydis. Recombinant Kin3 binds microtubules and has ATPase
      activity. Kin3-green fluorescent protein moves along microtubules in vivo,
      accumulates at sites of growth and localizes to endosomes. Deletion of kin3
      reduces endosome motility to approximately 33%, and abolishes endosome clustering
      at the distal cell pole and at septa. This results in a transition from bipolar
      to monopolar budding and cell separation defects. Double mutant analysis
      indicates that the remaining motility in Deltakin3-mutants depends on dynein, and
      that dynein and Kin3 counteract on the endosomes to arrange them at opposing cell
      poles.

PMID- 12065409
TI  - A novel type of co-chaperone mediates transmembrane recruitment of DnaK-like
      chaperones to ribosomes.
AB  - Recently, the homolog of yeast protein Sec63p was identified in dog pancreas
      microsomes. This pancreatic DnaJ-like protein was shown to be an abundant
      protein, interacting with both the Sec61p complex and lumenal DnaK-like proteins,
      such as BiP. The pancreatic endoplasmic reticulum contains a second DnaJ-like
      membrane protein, which had been termed Mtj1p in mouse. Mtj1p is present in
      pancreatic microsomes at a lower concentration than Sec63p but has a higher
      affinity for BiP. In addition to a lumenal J-domain, Mtj1p contains a single
      transmembrane domain and a cytosolic domain which is in close contact with
      translating ribosomes and appears to have the ability to modulate translation.
      The interaction with ribosomes involves a highly charged region within the
      cytosolic domain of Mtj1p. We propose that Mtj1p represents a novel type of co
      chaperone, mediating transmembrane recruitment of DnaK-like chaperones to
      ribosomes and, possibly, transmembrane signaling between ribosomes and DnaK-like
      chaperones of the endoplasmic reticulum.

PMID- 12065410
TI  - An intracellular proton sensor commands lipid- and mechano-gating of the K(+)
      channel TREK-1.
AB  - The 2P domain K(+) channel TREK-1 is widely expres sed in the nervous system. It
      is opened by a variety of physical and chemical stimuli including membrane
      stretch, intracellular acidosis and polyunsaturated fatty acids. This activation
      can be reversed by PKA-mediated phosphorylation. The C-terminal domain of TREK-1
      is critical for its polymodal function. We demonstrate that the conversion of a
      specific glutamate residue (E306) to an alanine in this region locks TREK-1 in
      the open configuration and abolishes the cAMP/PKA down-modulation. The E306A
      substitution mimics intracellular acidosis and rescues both lipid- and mechano
      sensitivity of a loss-of-function truncated TREK-1 mutant. We conclude that
      protonation of E306 tunes the TREK-1 mechanical setpoint and thus sets lipid
      sensitivity.

PMID- 12065411
TI  - Gain control of N-methyl-D-aspartate receptor activity by receptor-like protein
      tyrosine phosphatase alpha.
AB  - Src kinase regulation of N-methyl-D-aspartate (NMDA) subtype glutamate receptors
      in the central nervous system (CNS) has been found to play an important role in
      processes related to learning and memory, ethanol sensitivity and epilepsy.
      However, little is known regarding the mechanisms underlying the regulation of
      Src family kinase activity in the control of NMDA receptors. Here we report that
      the distal phosphatase domain (D2) of protein tyrosine phosphatase alpha
      (PTPalpha) binds to the PDZ2 domain of post-synaptic density 95 (PSD95). Thus,
      Src kinase, its activator (PTPalpha) and substrate (NMDA receptors) are linked by
      the same scaffold protein, PSD95. Removal of PTPalpha does not affect the
      association of Src with NMDA receptors, but turns off the constitutive regulation
      of NMDA receptors by the kinase. Further more, we found that application of the
      PTPalpha catalytic domains (D1 + D2) into neurones enhances NMDA receptor
      mediated synaptic responses. Conversely, the blockade of endogenous PTPalpha
      inhibits NMDA receptor activity and the induction of long-term potentiation in
      hippocampal neurones. Thus, PTPalpha is a novel up-regulator of synaptic strength
      in the CNS.

PMID- 12065412
TI  - PICK1 is required for the control of synaptic transmission by the metabotropic
      glutamate receptor 7.
AB  - Both postsynaptic density and presynaptic active zone are structural matrix
      containing scaffolding proteins that are involved in the organization of the
      synapse. Little is known about the functional role of these proteins in the
      signaling of presynaptic receptors. Here we show that the interaction of the
      presynaptic metabotropic glutamate (mGlu) receptor subtype, mGlu7a, with the
      postsynaptic density-95 disc-large zona occludens 1 (PDZ) domain-containing
      protein, PICK1, is required for specific inhibition of P/Q-type Ca(2+) channels,
      in cultured cerebellar granule neurons. Furthermore, we show that activation of
      the presynaptic mGlu7a receptor inhibits synaptic transmission and this effect
      also requires the presence of PICK1. These results indicate that the scaffolding
      protein, PICK1, plays an essential role in the control of synaptic transmission
      by the mGlu7a receptor complex.

PMID- 12065413
TI  - DNA damage-induced apoptosis requires the DNA-dependent protein kinase, and is
      mediated by the latent population of p53.
AB  - Mouse embryo fibroblasts (MEFs) expressing the adenovirus E1A protein undergo
      apoptosis upon exposure to ionizing radiation. We show here that immediately
      following gamma-irradiation, latent p53 formed a complex with the catalytic
      subunit of the DNA-dependent protein kinase (DNA-PK(CS)). The complex formation
      was DNase sensitive, suggesting that the proteins came together on the DNA,
      conceivably at strand breaks. This association was accompanied by phosphorylation
      of pre-existing, latent p53 at Ser18 (corresponding to Ser15 in human p53), which
      was not found in DNA-PK(CS)(-/-) cells. Most significantly, DNA damage-induced
      apoptosis was abolished in both DNA-PK(CS)(-/-) and p53(-/-) cells. In addition,
      blocking synthesis of inducible p53 by cycloheximide did not abrogate apoptosis,
      suggesting that the latent population of p53 is sufficient for executing the
      apoptotic program. Finally, E1A-expressing MEFs from a p53 "knock-in" mouse where
      Ser18 was mutated to an alanine had an attenuated apoptotic response, indicating
      that phosphorylation of this site by DNA-PK is a contributing factor for
      apoptosis.

PMID- 12065414
TI  - Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway.
AB  - Drosophila provides a powerful genetic model for studying the in vivo regulation
      of cell death. In our large-scale gain-of-function screen, we identified Eiger,
      the first invertebrate tumor necrosis factor (TNF) superfamily ligand that can
      induce cell death. Eiger is a type II transmembrane protein with a C-terminal TNF
      homology domain. It is predominantly expressed in the nervous system. Genetic
      evidence shows that Eiger induces cell death by activating the Drosophila JNK
      pathway. Although this cell death process is blocked by Drosophila inhibitor-of
      apoptosis protein 1 (DIAP1), it does not require caspase activity. We also show
      genetically that Eiger is a physiological ligand for the Drosophila JNK pathway.
      Our findings demonstrate that Eiger can initiate cell death through an IAP
      sensitive cell death pathway via JNK signaling.

PMID- 12065415
TI  - Prohibitin requires Brg-1 and Brm for the repression of E2F and cell growth.
AB  - E2F transcription factors play a major role in controlling mammalian cell cycle
      progression. We recently reported that a potential tumor suppressor, prohibitin,
      which interacts with retinoblastoma protein (Rb), regulates E2F function and this
      activity correlates with its growth-suppressive activity. We show here that
      prohibitin recruits Brg-1/Brm to E2F-responsive promoters, and that this
      recruitment is required for the repression of E2F-mediated transcription by
      prohibitin. Expression of a dominant-negative Brg-1 or Brm releases prohibitin
      mediated repression of E2F and relieves prohibitin-mediated growth suppression.
      Although prohibitin associates with, and recruits, Brg-1 and Brm independently of
      Rb, prohibitin/Brg-1/Brm-mediated transcriptional repression requires Rb. A viral
      oncoprotein, SV40 large T antigen, can reverse prohibitin-mediated suppression of
      E2F-mediated gene transcription, and targets prohibitin through interruption of
      the association between prohibitin and Brg-1/Brm without affecting the prohibitin
      E2F interaction.

PMID- 12065416
TI  - Homeodomain protein ATHB6 is a target of the protein phosphatase ABI1 and
      regulates hormone responses in Arabidopsis.
AB  - ABI1, a protein phosphatase 2C, is a key component of signal transduction in
      Arabidopsis. It regulates diverse responses to the phytohormone abscisic acid
      (ABA) such as stomatal closure, seed dormancy and inhibition of vegetative
      growth. By analysing proteins capable of interacting with ABI1, we have
      identified the homeodomain protein ATHB6 as a regulator of the ABA signal
      pathway. Critical for interaction between ATHB6 and ABI1 is an intact protein
      phosphatase domain and the N-terminal domain of ATHB6 containing the DNA-binding
      site. ATHB6 recognizes a cis-element present in its promoter, which encompasses
      the core motif (CAATTATTA) that mediated ATHB6- and ABA-dependent gene expression
      in protoplasts. In addition, transgenic plants containing a luciferase gene
      controlled by the ATHB6 promoter documented a strong ABA-inducible expression of
      the reporter which was abrogated in the ABA-insensitive abi1 mutant. Arabidopsis
      plants with constitutive expression of the transcriptional regulator revealed ABA
      insensitivity in a subset of ABI1-dependent responses. Thus, the homeodomain
      protein ATHB6 seems to represent a negative regulator of the ABA signal pathway
      and to act downstream of ABI1.

PMID- 12065417
TI  - Establishing the transcriptional programme for blood: the SCL stem cell enhancer
      is regulated by a multiprotein complex containing Ets and GATA factors.
AB  - Stem cells are a central feature of metazoan biology. Haematopoietic stem cells
      (HSCs) represent the best-characterized example of this phenomenon, but the
      molecular mechanisms responsible for their formation remain obscure. The stem
      cell leukaemia (SCL) gene encodes a basic helix-loop-helix (bHLH) transcription
      factor with an essential role in specifying HSCs. Here we have addressed the
      transcriptional hierarchy responsible for HSC formation by characterizing an SCL
      3' enhancer that targets expression to HSCs and endothelium and their bipotential
      precursors, the haemangioblast. We have identified three critical motifs, which
      are essential for enhancer function and bind GATA-2, Fli-1 and Elf-1 in vivo. Our
      results suggest that these transcription factors are key components of an
      enhanceosome responsible for activating SCL transcription and establishing the
      transcriptional programme required for HSC formation.

PMID- 12065418
TI  - The basis for TCR-mediated regulation of the IL-2 receptor alpha chain gene: role
      of widely separated regulatory elements.
AB  - The interleukin-2 receptor alpha (IL-2Ralpha) chain is a component of high
      affinity IL-2 receptors and thus is a key regulator of lymphocyte proliferation.
      Lineage-restricted and activation-dependent IL-2Ralpha transcription is
      controlled by four upstream positive regulatory regions (PRRs) and one downstream
      PRR. We now demonstrate that T-cell receptor (TCR) responsiveness requires both
      upstream sequences and an intronic region, PRRIV, previously identified as an IL
      2 response element. Whereas IL-2 responsiveness requires Stat5 and HMG-I(Y)
      binding, TCR responsiveness of PRRIV requires two AP-1- and two NFAT-binding
      sites that bind Jun, Fos and NFAT family members in vitro and in vivo. Moreover,
      IL-2Ralpha induction is impaired in T lymphocytes from transgenic mice expressing
      a dominant-negative c-jun construct, or following treatment with cyclosporin A.
      Thus, our data indicate an important role for both AP-1 and NFAT proteins for TCR
      induced IL-2Ralpha expression and establish that both upstream and intronic
      sequences mediate TCR responsiveness of the IL-2Ralpha gene. Moreover, our data
      reveal a previously unappreciated link between the TCR-mediated up-regulation of
      the IL-2 and IL-2Ralpha genes.

PMID- 12065419
TI  - GATA-2 and GATA-2/ER display opposing activities in the development and
      differentiation of blood progenitors.
AB  - GATA-2 is a zinc finger transcription factor essential for the development of
      hematopoiesis. While GATA-2 is generally considered to play an important role in
      the biology of hematopoietic stem and progenitor cells, its function within these
      compartments is not well understood. Here we have employed both conditional
      expression of GATA-2 and conditional activation of a GATA-2/estrogen receptor
      (ER) chimera to examine the effect of enforced GATA-2 expression in the
      development and differentiation of hematopoietic progenitors from murine
      embryonic stem cells. Consistent with the phenotype of GATA-2 null animals,
      conditional expression of GATA-2 from a tetracycline-inducible promoter enhanced
      the production of hematopoietic progenitors. Conditional activation of a GATA
      2/ER chimera produced essentially opposite effects to those observed with
      conditional GATA-2 expression. GATA-2 and GATA-2/ER differ in their binding
      activities and transcriptional interactions from other hematopoietic-associated
      transcription factors such as c-Myb and PU.1. While we have exploited these
      differences in activity to explore the transcriptional networks underlying
      hematopoietic cell fate determination, our results suggest that care should be
      taken in interpreting results obtained using only chimeric proteins.

PMID- 12065420
TI  - A viral protein suppresses RNA silencing and binds silencing-generated, 21- to 25
      nucleotide double-stranded RNAs.
AB  - Posttranscriptional gene silencing (PTGS) processes double-stranded (ds) RNAs
      into 21-25 nucleotide (nt) RNA fragments that direct ribonucleases to target
      cognate mRNAs. In higher plants, PTGS also generates mobile signals conferring
      sequence-specific silencing in distant organs. Since PTGS acts as an antiviral
      system in plants, successful virus infection requires evasion or suppression of
      gene silencing. Here we report that the 19 kDa protein (p19) of tombusviruses is
      a potent silencing suppressor that prevents the spread of mobile silencing
      signal. In vitro, p19 binds PTGS-generated, 21-25 nt dsRNAs and 21-nt synthetic
      dsRNAs with 2-nt 3' overhanging end(s), while it barely interacts with single
      stranded (ss) RNAs, long dsRNAs or blunt-ended 21-nt dsRNAs. We propose that p19
      mediates silencing suppression by sequestering the PTGS-generated 21-25 nt
      dsRNAs, thus depleting the specificity determinants of PTGS effector complexes.
      Moreover, the observation that p19-expressing transgenic plants show altered leaf
      morphology might indicate that the p19-targeted PTGS pathway is also important in
      the regulation of plant development.

PMID- 12065421
TI  - Homolog interaction during meiotic prophase I in Arabidopsis requires the SOLO
      DANCERS gene encoding a novel cyclin-like protein.
AB  - Interactions between homologs in meiotic prophase I, such as recombination and
      synapsis, are critical for proper homolog segregation and involve the
      coordination of several parallel events. However, few regulatory genes have been
      identified; in particular, it is not clear what roles the proteins similar to the
      mitotic cell cycle regulators might play during meiotic prophase I. We describe
      here the isolation and characterization of a new Arabidopsis mutant called solo
      dancers that exhibits a severe defect in homolog synapsis, recombination and
      bivalent formation in meiotic prophase I, subsequently resulting in seemingly
      random chromosome distribution and formation of abnormal meiotic products. We
      further demonstrate that the mutation affects a meiosis-specific gene encoding a
      novel protein of 578 amino acid residues with up to 31% amino acid sequence
      identity to known cyclins in the C-terminal portion. These results argue strongly
      that homolog interactions during meiotic prophase I require a novel meiosis
      specific cyclin in Arabidopsis.

PMID- 12065422
TI  - Schizosaccharomyces pombe NIMA-related kinase, Fin1, regulates spindle formation
      and an affinity of Polo for the SPB.
AB  - The Aspergillus nidulans protein kinase NIMA regulates mitotic commitment, while
      the human and Xenopus equivalents influence centrosome function. Two recessive,
      temperature-sensitive mutations in the Schizosaccharomyces pombe NIMA homologue,
      Fin1, blocked spindle formation at 37 degrees C. One of the two spindle pole
      bodies (SPBs) failed to nucleate microtubules. This phenotype was reduced by
      accelerating mitotic commitment through genetic inhibition of Wee1 or activation
      of either Cdc25 or Cdc2. Polo kinase (Plo1) normally associates with the SPB of
      mitotic, but not interphase cells. cut12.s11 is a dominant mutation in an SPB
      component that both suppresses cdc25 mutants and promotes Plo1 association with
      the interphase SPB. Both cut12.s11 phenotypes were abolished by removing Fin1
      function. Elevating Fin1 levels promoted Plo1 recruitment to the interphase SPB
      of wild-type cells and reduced the severity of the cdc25.22 phenotype. These data
      are consistent with Fin1 regulating Plo1 function during mitotic commitment. The
      fin1 mitotic commitment and spindle phenotypes resemble distinct nimA phenotypes
      in different systems and suggest that the function of this family of kinases may
      be conserved across species.

PMID- 12065423
TI  - Cell cycle-dependent localization of two novel prokaryotic chromosome segregation
      and condensation proteins in Bacillus subtilis that interact with SMC protein.
AB  - Disruption of ypuG and ypuH open reading frames in Bacillus subtilis leads to
      temperature-sensitive slow growth, a defect in chromosome structure and formation
      of anucleate cells. The genes, which were named scpA and scpB, were found to be
      epistatic to the smc gene. Fusions of ScpA and ScpB to the fluorescent proteins
      YFP or CFP showed that both proteins co-localize to two or four discrete foci
      that were present at mid-cell in young cells, and within both cell halves,
      generally adjacent to chromosomal origin regions, in older cells. ScpA and ScpB
      foci are associated with DNA and depend on the presence of SMC and both Scps.
      ScpA and ScpB are associated with each other and with SMC in vivo, as determined
      using the FRET technique and immunoprecipitation assays. Genes similar to scpA
      and scpB are present in many bacteria and archaea, which suggests that their gene
      products form a condensation complex with SMC in most prokaryotes. The observed
      foci could constitute condensation factories that pull DNA away from mid-cell
      into both cell halves.

PMID- 12065424
TI  - Prokaryotic DNA segregation by an actin-like filament.
AB  - The mechanisms responsible for prokaryotic DNA segregation are largely unknown.
      The partitioning locus (par) encoded by the Escherichia coli plasmid R1 actively
      segregates its replicon to daughter cells. We show here that the ParM ATPase
      encoded by par forms dynamic actin-like filaments with properties expected for a
      force-generating protein. Filament formation depended on the other components
      encoded by par, ParR and the centromere-like parC region to which ParR binds.
      Mutants defective in ParM ATPase exhibited hyperfilamentation and did not support
      plasmid partitioning. ParM polymerization was ATP dependent, and depolymerization
      of ParM filaments required nucleotide hydrolysis. Our in vivo and in vitro
      results indicate that ParM polymerization generates the force required for
      directional movement of plasmids to opposite cell poles and that the ParR-parC
      complex functions as a nucleation point for ParM polymerization. Hence, we
      provide evidence for a simple prokaryotic analogue of the eukaryotic mitotic
      spindle apparatus.

PMID- 12065425
TI  - R-loop-dependent rolling-circle replication and a new model for DNA concatemer
      resolution by mitochondrial plasmid mp1.
AB  - The mitochondrial (mt) plasmid mp1 of Chenopodium album replicates by a rolling
      circle (RC) mechanism initiated at two double-stranded replication origins (dso1
      and dso2). Two-dimensional gel electrophoresis and electron microscopy of early
      mp1 replication intermediates revealed novel spots. Ribonucleotide (R)-loops were
      identified at dso1, which function as a precursor for the RCs in vivo and in
      vitro. Bacteriophage T4-like networks of highly branched mp1 concatemers with up
      to 20 monomer units were mapped and shown to be mainly formed by replicating,
      invading, recombining and resolving molecules. A new model is proposed in which
      concatemers were separated into single units by a "snap-back" mechanism and
      homologous recombination. dso1 is a recombination hotspot, with sequence homology
      to bacterial Xer recombination cores. mp1 is a unique eukaryotic plasmid that
      expresses features of phages like T4 and could serve as a model system for
      replication and maintenance of DNA concatemers.

PMID- 12065426
TI  - Essential bacterial helicases that counteract the toxicity of recombination
      proteins.
AB  - PcrA, Rep and UvrD are three closely related bacterial helicases with a DExx
      signature. PcrA is encoded by Gram-positive bacteria and is essential for cell
      growth. Rep and UvrD are encoded by Gram-negative bacteria, and mutants lacking
      both helicases are also not viable. To understand the non-viability of the
      helicase mutants, we characterized spontaneous extragenic suppressors of a
      Bacillus subtilis pcrA null mutation. Here we report that one of these
      suppressors maps in recF and that previously isolated mutations in B.subtilis
      recF, recL, recO and recR, which belong to the same complementation group, all
      suppress the lethality of a pcrA mutation. Similarly, recF, recO or recR
      mutations suppress the lethality of the Escherichia coli rep uvrD double mutant.
      We conclude that RecFOR proteins are toxic in cells devoid of PcrA in Gram
      positive bacteria, or Rep and UvrD in Gram-negative bacteria, and propose that
      the RecFOR proteins interfere with an essential cellular process, possibly
      replication, when DExx helicases PcrA, or Rep and UvrD are absent.

PMID- 12065427
TI  - The DnaC helicase loader is a dual ATP/ADP switch protein.
AB  - Helicases are transferred to replication origins by helicase loading factors. The
      Escherichia coli DnaC and eukaryotic Cdc6/18 helicase loaders contain ATP sites
      and are both members of the AAA+ family. One might expect that ATP is required
      for helicase loading; however, this study on DnaC illustrates that ATP is not
      actually needed for DnaC to load helicase onto single-strand DNA (ssDNA). In
      fact, it seems to be a paradox that after transfer of helicase to DNA, DnaC-ATP
      inhibits helicase action. In addition, ATP is required for DnaC function at an
      early step in oriC replication in which ATP stimulates ssDNA binding by DnaC,
      leading to expansion of the ssDNA bubble at the origin. Two cofactors, ssDNA and
      DnaB, trigger hydrolysis of ATP, converting DnaC to the ADP form that no longer
      inhibits DnaB. These observations have led to the idea that DnaC is a 'dual'
      switch protein, where both the ATP and the ADP forms are sequentially required
      for replication. This dual switching process may underlie the sensitivity of DnaB
      to even small fluctuations in DnaC levels.

PMID- 12065428
TI  - Mutations in yeast Rad51 that partially bypass the requirement for Rad55 and
      Rad57 in DNA repair by increasing the stability of Rad51-DNA complexes.
AB  - Yeast Rad51 promotes homologous pairing and strand exchange in vitro, but this
      activity is inefficient in the absence of the accessory proteins, RPA, Rad52,
      Rad54 and the Rad55-Rad57 heterodimer. A class of rad51 alleles was isolated that
      suppresses the requirement for RAD55 and RAD57 in DNA repair, but not the other
      accessory factors. Five of the six mutations isolated map to the region of Rad51
      that by modeling with RecA corresponds to one of the DNA-binding sites. The other
      mutation is in the N-terminus of Rad51 in a domain implicated in protein-protein
      interactions and DNA binding. The Rad51-I345T mutant protein shows increased
      binding to single- and double-stranded DNA, and is proficient in displacement of
      replication protein A (RPA) from single-stranded DNA, suggesting that the normal
      function of Rad55-Rad57 is promotion and stabilization of Rad51-ssDNA complexes.

PMID- 12065429
TI  - Drf1, a novel regulatory subunit for human Cdc7 kinase.
AB  - Studies in model organisms have contributed to elucidate multiple levels at which
      regulation of eukaryotic DNA replication occurs. Cdc7, an evolutionarily
      conserved serine-threonine kinase, plays a pivotal role in linking cell cycle
      regulation to genome duplication, being essential for the firing of DNA
      replication origins. Binding of the cell cycle-regulated subunit Dbf4 to Cdc7 is
      necessary for in vitro kinase activity. This binding is also thought to be the
      key regulatory event that controls Cdc7 activity in cells. Here, we describe a
      novel human protein, Drf1, related to both human and yeast Dbf4. Drf1 is a
      nuclear cell cycle-regulated protein, it binds to Cdc7 and activates the kinase.
      Therefore, human Cdc7, like cyclin-dependent kinases, can be activated by
      alternative regulatory subunits. Since the Drf1 gene is either absent or not yet
      identified in the genome of model organisms such as yeast and Drosophila, these
      findings introduce a new level of complexity in the regulation of DNA replication
      of the human genome.

PMID- 12065430
TI  - A novel uracil-DNA glycosylase with broad substrate specificity and an unusual
      active site.
AB  - Uracil-DNA glycosylases (UDGs) catalyse the removal of uracil by flipping it out
      of the double helix into their binding pockets, where the glycosidic bond is
      hydrolysed by a water molecule activated by a polar amino acid. Interestingly,
      the four known UDG families differ in their active site make-up. The activating
      residues in UNG and SMUG enzymes are aspartates, thermostable UDGs resemble UNG
      type enzymes, but carry glutamate rather than aspartate residues in their active
      sites, and the less active MUG/TDG enzymes contain an active site asparagine. We
      now describe the first member of a fifth UDG family, Pa-UDGb from the
      hyperthermophilic crenarchaeon Pyrobaculum aerophilum, the active site of which
      lacks the polar residue that was hitherto thought to be essential for catalysis.
      Moreover, Pa-UDGb is the first member of the UDG family that efficiently
      catalyses the removal of an aberrant purine, hypoxanthine, from DNA. We postulate
      that this enzyme has evolved to counteract the mutagenic threat of cytosine and
      adenine deamination, which becomes particularly acute in organisms living at
      elevated temperatures.

PMID- 12065431
TI  - Synapsis of DNA ends by DNA-dependent protein kinase.
AB  - The catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) is required
      for a non-homologous end-joining pathway that repairs DNA double-strand breaks
      produced by ionizing radiation or V(D)J recombination; however, its role in this
      pathway has remained obscure. Using a neutravidin pull-down assay, we found that
      DNA-PK(CS) mediates formation of a synaptic complex containing two DNA molecules.
      Furthermore, kinase activity was cooperative with respect to DNA concentration,
      suggesting that activation of the kinase occurs only after DNA synapsis. Electron
      microscopy revealed complexes of two DNA ends brought together by two DNA-PK(CS)
      molecules. Our results suggest that DNA-PK(CS) brings DNA ends together and then
      undergoes activation of its kinase, presumably to regulate subsequent steps for
      processing and ligation of the ends.

PMID- 12065432
TI  - Instability of the human minisatellite CEB1 in rad27Delta and dna2-1 replication
      deficient yeast cells.
AB  - Convergent studies in human and yeast model systems have shown that some
      minisatellite loci are relatively stable in somatic cells but not in the
      germline, and little is known about the mechanism(s) that can destabilize them.
      Unlike microsatellite sequences, mini satellites are not destabilized by mismatch
      repair mutations. We report here that the absence of Rad27 and Dna2 functions but
      not RNase H(35) or Exo1, which play an essential role in the processing of
      Okazaki fragments during replication, destabilize the human minisatellite CEB1 in
      mitotically growing Saccharomyces cerevisiae cells, up to 14% per generation in
      rad27Delta cells. Analysis using minisatellite variant repeat mapping by
      polymerase chain reaction of the internal structure of 17 variants reveals that
      the majority of rearrangements in rad27Delta cells are extremely complex
      contraction events that contain deletions, often accompanied by duplications of
      motif unit. Altogether, these results suggest that the improperly processed 5'
      flap structures that accumulate when replication is impaired can act as a potent
      stimulator of minisatellite destabilization and can provoke an unexpectedly broad
      range of mutagenic events. This replication-dependent phenomenon differs from the
      recombination-induced instability in yeast meiotic cells.

PMID- 12065433
TI  - Phosphorodiamidate morpholino antisense oligomers inhibit expression of human
      cytochrome P450 3A4 and alter selected drug metabolism.
AB  - Antisense phosphorodiamidate morpholino oligomers (PMO) inhibit targeted gene
      expression by preventing ribosomal assembly, thus preventing translation.
      Inhibition of cytochrome P450 (P450) 3A4 expression was examined in primary human
      hepatocytes from 11 donors and in Caco-2 cells (stably transfected with CYP3A4
      cDNA on an extrachromosomal vector) by evaluating the metabolism of substrate 7
      benzyloxy-4-[trifluoromethyl]-coumarin and Western immunoblot analysis. Cellular
      uptake of PMO was confirmed in both cell systems using fluorescein-labeled PMOs.
      Three antisense PMO sequences and two control PMO sequences were tested. AVI
      4557, a 20-mer PMO with the sequence 5'-CTGGGATGAGAGCCATCACT-3' was selected as
      the optimal agent. AVI-4557 inhibited expression of CYP3A4 in Caco-2/h3A4 cells
      by 64% at 24 h following administration of 2.8 microM by an assisted delivery
      protocol. Inhibition of CYP3A activity was observed in primary human hepatocytes
      after 24 h exposure to AVI-4557 by an average of 32 +/- 11%. Furthermore, AVI
      4557 exposure resulted in a sequence-dependent inhibition of cyclophosphamide
      related cytocidal activity and a sequence-dependent induction of paclitaxel
      related cytocidal activity in both cell types. Finally, the cytocidal activity of
      cisplatin was not affected with AVI-4557 treatment in either cell type. These
      studies indicate AVI-4557 is an effective and specific inhibitor of CYP3A4
      expression.

PMID- 12065434
TI  - Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells
      overexpressing efflux transporters Pgp, cMOAT, and MRP1.
AB  - Irinotecan (CPT-11) is a water-soluble camptothecin (CPT) derivative that has
      been recently approved in the United States for patients as a first-line therapy
      in advanced colorectal cancer. Phase I clinical trials using oral CPT-11 have
      shown poor and variable oral bioavailability. The present study was designed to
      investigate the intestinal absorption and efflux mechanisms of CPT-11 using in
      vitro cell culture models, Caco-2 cells, and engineered Madine-Darby canine
      kidney (MDCK) II cells overexpressing P-glycoprotein (Pgp), canalicular
      multispecific organic anion transporter (cMOAT), and multidrug resistance
      associated protein (MRP1). The intestinal absorptive and secretory transport of
      CPT-11 was investigated using Caco-2 cell monolayers. Secretory transport was
      concentration-dependent and saturable. The secretory efflux permeability (P(eff))
      of CPT-11 decreased with decreasing temperature, with an estimated activation
      energy of 19.6 +/- 2.9 kcal/mol suggesting the involvement of active
      transporters. The involvement of potential secretory transporters was further
      characterized in MDCK II cells. The secretory efflux carrier permeability (P(c))
      was approximately 4- and approximately 2-fold greater in MDCK II/Pgp and MDCK
      II/cMOAT cells than that in MDCK II/wild-type cells. Furthermore, the secretory
      efflux P(eff) of CPT-11 was significantly decreased by Pgp inhibitors, elacridar
      (GF120918) (IC50 = 0.38 +/- 0.06 microM) and verapamil (IC(50) = 234 +/- 48
      microM) in MDCK II/Pgp cells and by cMOAT inhibitor 3-([(3-(2-[7-chloro-2
      quinolinyl]ethyl)phenyl]-[(3-dimethylamino-3-oxoprphyl)-thio)-methyl]-thio)
      propanoic acid (MK571) (IC50) = 469 +/- 60 micro;M) in MDCK II/cMOAT cells.
      Overall, the current study suggests that Pgp and cMOAT are capable of mediating
      the efflux of CPT-11 in vitro. Since both Pgp and cMOAT are expressed in the
      intestine, liver, and kidney, it is likely that these efflux transporters play a
      significant role limiting the oral absorption and disposition of this important
      anticancer drug.

PMID- 12065435
TI  - The pharmacokinetics of a thiazole benzenesulfonamide beta 3-adrenergic receptor
      agonist and its analogs in rats, dogs, and monkeys: improving oral
      bioavailability.
AB  - The pharmacokinetics and oral bioavailability of (R)-N-[4-[2-[[2-hydroxy-2
      (pyridin-3-yl)ethyl]amino]ethyl]phenyl]-4-[4-[4-(trifluoromethylphenyl]thiazol-2
      yl]benzenesulfonamide (1), a 3-pyridyl thiazole benzenesulfonamide beta3
      adrenergic receptor agonist, were investigated in rats, dogs, and monkeys.
      Systemic clearance was higher in rats (approximately 30 ml/min/kg) than in dogs
      and monkeys (both approximately 10 ml/min/kg), and oral bioavailability was 17,
      27, and 4%, respectively. Since systemic clearance was 25 to 40% of hepatic blood
      flow in these species, hepatic extraction was expected to be low, and it was
      likely that oral bioavailability was limited either by absorption or a large
      first-pass effect in the gut. The absorption and excretion of 3H-labeled 1 were
      investigated in rats, and only 28% of the administered radioactivity was orally
      absorbed. Subsequently, the hepatic extraction of 1 was evaluated in rats (30%)
      and monkeys (47%). The low oral bioavailability in rats could be explained
      completely by poor oral absorption and hepatic first-pass metabolism; in monkeys,
      oral absorption was either less than in rats or first-pass extraction in the gut
      was greater. In an attempt to increase oral exposure, the pharmacokinetics and
      oral bioavailability of two potential prodrugs of 1, an N-ethyl [(R)-N-[4-[2
      [ethyl[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]-4-[4-[4
      (trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide; 2] and a morpholine
      derivative [(R)-N-[4-[2-[2-(3-pyridinyl)morpholin-4-yl]ethyl]phenyl]-4-[4-[4
      (trifluoromethyl)- phenyl]thiazol-2-yl]benzenesulfonamide; 3], were evaluated in
      monkeys. Conversion to 1 was low (<3%) with both derivatives, and neither entity
      was an effective prodrug, but the oral bioavailability of 3 (56%) compared with 1
      (4%) was significantly improved. The hypothesis that the increased oral
      bioavailability of 3 was due to a reduction in hydrogen bonding sites in the
      molecule led to the design of (R)-N-[4-[2-[[2-hydroxy-2-(pyridin-2
      yl)ethyl]amino]ethyl]phenyl]-4-[4-(4-trifluoromethylphenyl)thiazol-2
      yl]benzenesulfonamide (4), a 2-pyridyl beta3-adrenergic receptor agonist with
      improved oral bioavailability in rats and monkeys.

PMID- 12065436
TI  - Metabolism of a thiazole benzenesulfonamide derivative, a potent and elective
      agonist of the human beta3-adrenergic receptor, in rats: identification of a
      novel isethionic acid conjugate.
AB  - (R)-N-[4-[2-[[2-Hydroxy-2-(pyridin-3-yl)ethyl]amino]ethyl]phenyl]- 4-[4-(4
      trifluoro-methylphenyl)thiazol-2-yl]benzenesulfonamide (1) is a potent and
      selective agonist of the human beta3-adrenergic receptor. We report herein the
      data from studies of the metabolism and excretion of 1 in rats. Five metabolites
      were identified in the bile of male Sprague-Dawley rats administered 3H-labeled 1
      by either oral gavage (10 mg/kg) or intravenous injection (3 mg/kg). These
      included a pyridine N-oxide derivative (M2), a primary amine resulting from N
      dealkylation and loss of the pyridinyl-2-hydroxyethyl group (M4), a carboxylic
      acid derived from N-dealkylation and loss of the pyridyl-2-hydroxyethyl amine
      (M5), and the corresponding taurine and isethionic acid conjugates (M1 and M3).
      Metabolites M1 and M3 also were identified in rats treated with M5 and were
      generated in incubations of M5 with rat liver subcellular fractions in the
      presence of ATP and coenzyme A with supplementary taurine or isethionic acid.
      These results suggest that M5 is the precursor of M1 and M3 and that the
      formation of these conjugated metabolites follows similar mechanisms of amino
      acid conjugation. On the other hand, M2, M4, and M5 were produced from 1 in an
      NADPH-dependent manner in incubations with liver microsomes from rats, dogs,
      monkeys, and humans. In human liver preparations, these routes of
      biotransformation were shown to be catalyzed by cytochrome P450 3A4. In a
      bidirectional transport assay, transport of 1 across a monolayer of cells
      expressing P-glycoprotein (Pgp) was observed to be similar to that of
      vinblastine, which is an established substrate of the transporter protein. This
      finding, together with the observation that the parent compound was excreted in
      the feces of bile duct-cannulated animals following intravenous dosing, suggests
      that 1 is subject to Pgp-mediated excretion from intestine of rats.

PMID- 12065437
TI  - Identification of human hepatic cytochrome P450 sources of N-alkylprotoporphyrin
      IX after interaction with porphyrinogenic xenobiotics, implications for detection
      of xenobiotic-induced porphyria in humans.
AB  - Porphyrinogenicity of certain xenobiotics depends upon mechanism-based
      inactivation of specific cytochrome P450 (P450) enzymes, followed by formation of
      N-alkylprotoporphyrin IX (N-alkylPP). Examination of the porphyrinogenicity of
      xenobiotics in animals and extrapolation of the results to humans is associated
      with ambiguity due, in part, to differences between P450 enzymes. The goal of
      this study was to develop an in vitro test for the detection of N-alkylPPs,
      produced in human liver after administration of xenobiotics found to be
      porphyrinogenic in animals. This goal was achieved using fluorometry to detect N
      alkylPP formation following mechanism-based inactivation by porphyrinogenic
      xenobiotics of single cDNA-expressed human P450 enzymes in microsomes prepared
      from baculovirus-infected insect cells (Supersomes) and in human liver
      microsomes. The following combinations of P450 enzymes were major sources of N
      alkylPPs in Supersomes: CYP3A4 [3-[(arylthio)-ethyl]sydnone (TTMS)]; CYP1A2 and
      2C9 [3,5-diethoxycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyridine (4-ethyl
      DDC)]; and CYP2C9, 2D6, and 3A4 [allylisopropylacetamide (AIA)]. Whereas
      similarities were found between results with human enzymes in Supersomes and
      their rat orthologs in rat liver microsomes, some differences were found. The
      results with TTMS and AIA, but not with 4-ethyl DDC, were the same in individual
      human enzymes expressed in Supersomes and human liver microsomes. We conclude
      that some differences exist between human liver P450 enzymes and their rat P450
      orthologs in liver microsomes. It would therefore be prudent when dealing with
      xenobiotics in which porphyrinogenicity depends upon N-alkylPP formation to
      supplement animal data with studies using human P450 enzymes.

PMID- 12065438
TI  - CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter
      gene assay and CYP3A4 expression in human hepatocytes.
AB  - Induction of cytochrome P450 3A4 (CYP3A4) is determined typically by employing
      primary culture of human hepatocytes and measuring CYP3A4 mRNA, protein and
      microsomal activity. Recently a pregnane X receptor (PXR) reporter gene assay was
      established to screen CYP3A4 inducers. To evaluate results from the PXR reporter
      gene assay with those from the aforementioned conventional assays, 14 drugs were
      evaluated for their ability to induce CYP3A4 and activate PXR. Sandwiched primary
      cultures of human hepatocytes from six donors were used and CYP3A4 activity was
      assessed by measuring microsomal testosterone 6beta-hydroxylase activity. Hepatic
      CYP3A4 mRNA and protein levels were also analyzed using branched DNA
      technology/Northern blotting and Western blotting, respectively. In general, PXR
      activation correlated with the induction potential observed in human hepatocyte
      cultures. Clotrimazole, phenobarbital, rifampin, and sulfinpyrazone highly
      activated PXR and increased CYP3A4 activity; carbamazepine, dexamethasone,
      dexamethasone-t-butylacetate, phenytoin, sulfadimidine, and taxol weakly
      activated PXR and induced CYP3A4 activity, and methotrexate and probenecid showed
      no marked activation in either system. Ritonavir and troleandomycin showed marked
      PXR activation but no increase (in the case of troleandomycin) or a significant
      decrease (in the case of ritonavir) in microsomal CYP3A4 activity. It is
      concluded that the PXR reporter gene assay is a reliable and complementary method
      to assess the CYP3A4 induction potential of drugs and other xenobiotics.

PMID- 12065439
TI  - In vitro interactions between a potential muscle relaxant E2101 and human
      cytochromes P450.
AB  - E2101 or N-methyl-[1-[1-(2-fluorophenethyl)piperidine-4-yl]-1H-indol-6-yl]
      acetamide, an antagonist of 5-hydroxytryptamine receptor subtypes 1A and 2, is
      currently under development for the potential treatment of skeletal muscle
      associated spasticity. Here we characterized the in vitro metabolism of E2101
      using human liver enzymes including human liver microsomal preparations, human
      liver S9 fractions, and individual forms of recombinant cytochromes P450 (P450s).
      Our results showed that E2101 was metabolized by P450s to form monohydroxylated
      (M1 and M2), dihydroxylated (M3), and N-dealkylated metabolites (M4). The
      structures of these major microsomal metabolites were proposed based on LC/MS/MS
      analyses. All four metabolites, M1-M4, were formed by CYP3A4. Metabolites, M1,
      M2, and M4, were also formed by CYP2C19 and M2 and M3 by CYP2D6. The potential
      P450 inhibition and induction of E2101 were also evaluated. E2101 was determined
      to be a competitive inhibitor of CYP2C19 and CYP2D6 with K(i) of 15 and 48
      microM, respectively, as determined by both Dixon plots and simultaneously
      nonlinear regression analyses. Induction of major P450 expression was not
      detected immunochemically after 72-h exposure to 10 or 50 microM E2101 in primary
      hepatocyte cultures obtained from three subjects. Taken together, E2101 is
      expected to metabolically interact with major human P450 enzymes including
      CYP2C19, CYP2D6, and CYP3A4, and a low risk of drug-drug interaction would be
      anticipated in clinical studies.

PMID- 12065440
TI  - The effect of cyclophosphamide with and without dexamethasone on cytochrome P450
      3A4 and 2B6 in human hepatocytes.
AB  - The purpose of this study was to characterize the concentration-response effects
      of cyclophosphamide (CPA) with and without dexamethasone (DEX; 10 microM) on the
      expression of CYP3A4 and CYP2B6 in cultured human hepatocytes at concentrations
      representative of standard- and high-dose CPA therapy (25 to 750 microM). CPA
      produced concentration-dependent increases in CYP3A4 and CYP2B6 activity and
      immunoreactive protein that peaked at 250 and 125 microM, respectively, and
      declined thereafter. The inductive effect of CPA alone and in combination with
      DEX was greater in magnitude for CYP2B6 compared with CYP3A4. To further examine
      the inductive effect of CPA on CYP3A4, CPA (250 microM) and DEX (10 microM) alone
      and in combination were examined in 10 hepatocyte preparations. The combination
      of CPA and DEX yielded higher rates of 6beta-hydroxytestosterone formation than
      either agent alone. However, the effect was less than additive in human
      hepatocyte cultures with relatively high baseline CYP3A4 activity and additive or
      synergistic in human hepatocyte cultures with relatively low baseline CYP3A4
      activity. Induction index was highly correlated with CYP3A4 baseline activity for
      both CPA (r(2) = 0.75) and CPA plus DEX (r(2) = 0.85). To investigate the
      potential mechanism for CPA-induced increases in CYP3A4 activity, the ability of
      CPA alone and in combination with DEX to activate pregnane X receptor (PXR) was
      explored using transient transfection assays. CPA produced a dose-dependent
      increase in PXR activation that was maximal at the highest CPA concentration
      studied (500 microM). The addition of DEX to CPA resulted in a minor increase in
      PXR activation compared with CPA alone. These results indicate that CPA alone and
      in combination with DEX differentially induces the expression of CYP3A4 and 2B in
      a concentration-dependent manner, which may be mediated partially through
      activation of PXR. The impact of these effects on the efficacy and toxicity of
      CPA therapy warrants further investigation.

PMID- 12065441
TI  - Evaluation of accelerator mass spectrometry in a human mass balance and
      pharmacokinetic study-experience with 14C-labeled (R)-6-[amino(4- chlorophenyl)(1
      methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1- methyl-2(1H)-quinolinone
      (R115777), a farnesyl transferase inhibitor.
AB  - Accelerator mass spectrometry (AMS) has been used in a human mass balance and
      metabolism study to analyze samples taken from four healthy male adult subjects
      administered nanoCurie doses of the farnesyl transferase inhibitor 14C-labeled
      (R)-6-[amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)
      1-methyl-2(1H)-quinolinone ([14C]R115777). Plasma, urine, and feces samples were
      collected at fixed timepoints after oral administration of 50 mg [14C]R115777
      (25.4 Bq/mg or 687 pCi/mg i.e., equivalent to 76.257 x 10(3) dpm) per subject.
      AMS analysis showed that drug-related (14)C was present in the plasma samples
      with C(max) values ranging from 1.6055 to 2.9074 dpm/ml (1.0525-1.9047 microg/ml)
      at t(max) = 2 to 3 h. The C(max) values for acetonitrile extracts of plasma
      samples ranged from 0.3724 to 0.7490 dpm/ml in the four male subjects. Drug
      related 14C was eliminated from the body both in the urine and the feces, with a
      mean total recovery of 79.8 +/- 12.9% in the feces and 13.7 +/- 6.2% in the
      urine. The majority of drug-related radioactivity in urine and feces was excreted
      within the first 48 h. High-performance liquid chromatography (HPLC)-AMS profiles
      were generated from radioactive parent drug plus metabolites from pooled diluted
      urine, plasma, and methanolic feces extracts and matched to retention times of
      synthetic reference substances, postulated as metabolites. All HPLC separations
      used no more than 5 dpm injected on-column. The radioactive metabolite profiles
      obtained compared well with those obtained using liquid chromatography/tandem
      mass spectometry. This study demonstrates the use of AMS in a human phase I study
      in which the administered radioactive dose was at least 1000-fold lower than that
      used for conventional radioactive studies.

PMID- 12065442
TI  - Measurement of Michaelis constants for cytochrome P450-mediated biotransformation
      reactions using a substrate depletion approach.
AB  - The Michaelis constant (KM) for cytochrome P450-mediated drug biotransformation
      reactions can be an important parameter in understanding the potential for a drug
      to exhibit saturable metabolism in vivo and nonlinear dose-exposure
      relationships. KM values were measured for several drug biotransformation
      reactions using recombinant heterologously expressed human enzymes. These
      determinations were made using an approach of monitoring substrate loss ("in
      vitro t1/2" method) at multiple substrate concentrations, with the objective of
      comparing KM values determined by this approach with KM values determined using
      the conventional approach of measuring product formation rates at several
      substrate concentrations. The reactions examined were CYP2C9-catalyzed diclofenac
      4'-hydroxylation, CYP2D6-catalyzed dextromethorphan O-demethylation and
      thioridazine S-oxidation, CYP2C19-catalyzed imipramine N-demethylation, CYP3A4
      catalyzed midazolam 1'-hydroxylation, and CYP1A2-catalyzed tacrine 1
      hydroxylation. KM values spanned an 80-fold range from 0.12 microM (CYP2D6
      catalyzed thioridazine S-oxidation) to 9.8 microM (CYP2C19-catalyzed imipramine N
      demethylation). On average, KM values determined by the substrate depletion
      approach were within 1.54-fold of those determined by measuring product
      formation. Thus, KM values can be determined for drug metabolism reactions
      without requiring knowledge of metabolite structures or requiring authentic
      standards of metabolites for use in construction of standard curves for
      quantitative bioanalysis. The in vitro t1/2 approach of determining KM values
      should be useful in early drug discovery efforts to identify those compounds with
      low KM values and, hence, a greater probability of exhibiting supraproportional
      dose-exposure relationships.

PMID- 12065443
TI  - Tissue distribution and chemical induction of multiple drug resistance genes in
      rats.
AB  - Multiple drug resistance (mdr) genes encode P-glycoprotein, which is responsible
      for resistance to some cancer chemotherapeutic drugs and efflux of xenobiotics of
      cells. Thus, mdr can protect organs from xenobiotics. In rats, there are two mdr1
      genes capable of xenobiotic transport, mdr1a and mdr1b. The purpose of this study
      was to determine the tissue distribution of rat mdr1a and mdr1b mRNA and whether
      microsomal enzyme inducers that increase phase I and II drug-metabolizing enzymes
      coordinately regulate mdr1a and/or mdr1b. The mRNA levels of mdr1a and mdr1b were
      determined using branched-DNA signal amplification technology. The highest level
      of expression of mdr1a mRNA was observed in the gastrointestinal tract, with
      levels increasing, respectively, from duodenum, jejunum, and ileum to large
      intestine. Expression levels of mdr1a mRNA in the cerebral cortex, cerebellum,
      kidney, lung, and liver were less than one-tenth of that in the ileum. The tissue
      distribution of mdr1b mRNA was similar to mdr1a with highest expression in the
      gastrointestinal tract but only about 3-fold higher than in most other tissues.
      The induction of mdr1a and mdr1b mRNA transcripts in liver, kidney, and ileum by
      treatment of rats with 18 chemicals representing aryl hydrocarbon receptor
      ligands, constitutive androstane receptor ligands, pregnane X receptor ligands,
      peroxisome proliferator-activated receptor ligands, electrophile-response-element
      activators, and CYP4502E1 inducers was assessed. Hepatic, renal, and intestinal
      expression of mdr1a and mdr1b mRNA were not significantly altered by treatment of
      rats with any of these classes of ligands. In conclusion, the primary expression
      of rat mdr1 genes is in the gastrointestinal tract where they are thought to
      function to decrease the absorption of some xenobiotics. Rat mdr1 gene expression
      is not readily increased by microsomal enzyme inducers in rats through coordinate
      mechanisms with phase I and II drug-metabolizing enzymes.

PMID- 12065444
TI  - Cytochrome P450 fluorometric substrates: identification of isoform-selective
      probes for rat CYP2D2 and human CYP3A4.
AB  - We have tested a panel of 29 cDNA-expressed rat and human enzymes with 9
      fluorometric substrates to determine the P450 isoform selectivity in the
      catalysis of the substrates to fluorescent products. The substrates examined were
      dibenzyl fluorescein, 7-benzyloxyquinoline (BQ), 3-cyano-7-ethoxycoumarin, 3
      cyano-7-methoxycoumarin, 7-methoxy-4-trifluoromethylcoumarin, 3-[2-(N,N-diethyl-N
      methylamino)ethyl]-7-methoxy-4-methylcoumarin (AMMC), 3-[2-(N,N-diethyl-N
      methylamino)ethyl]-7-methoxy-4-trifluoromethylcoumarin, 7-benzyloxyresorufin, and
      7-benzyloxy-4-trifluoromethylcoumarin (BFC). For most substrates, multiple cDNA
      expressed cytochrome P450 isoforms were found to catalyze the formation of the
      fluorescent product. However, among the combinations tested, rat CYP2D2 displayed
      high selectivity for AMMC demethylation (a substrate selective for CYP2D6 in
      human liver microsomes). AMMC demethylation activity was 15-fold lower in
      microsomes isolated from female Dark Agouti rats, a model known to have a low
      abundance of CYP2D2, and apparent K(M) values were similar for cDNA-expressed
      CYP2D2 and male Sprague-Dawley liver microsomes. BFC dealkylation and BQ
      dealkylation were selective but not exclusive for human CYP3A4. A small role for
      CYP1A2 could be demonstrated. The CYP3A4 selectivity in hepatic microsomes was
      supported by studies using chemical and antibody inhibitors and a correlation
      analysis within a panel of liver microsomes from individual donors. BQ
      demonstrated a higher degree of selectivity for and higher rates of metabolism by
      CYP3A than BFC. However, per unit enzyme the fluorescent signal is lower for BQ
      than BFC. AMMC, BQ, and BFC should find uses as enzyme-selective probe
      substrates.

PMID- 12065445
TI  - Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of
      ketamine in human liver microsomes.
AB  - Ketamine is a widely used drug for its anesthetic and analgesic properties; it is
      also considered as a drug of abuse, as many cases of ketamine illegal consumption
      were reported. Ketamine is N-demethylated by liver microsomal cytochrome P450
      into norketamine. The identification of the enzymes responsible for ketamine
      metabolism is of great importance in clinical practice. In the present study, we
      investigated the metabolism of ketamine in human liver microsomes at clinically
      relevant concentrations. Liver to plasma concentration ratio of ketamine was
      taken into consideration. Pooled human liver microsomes and human lymphoblast
      expressed P450 isoforms were used. N-demethylation of ketamine was correlated
      with nifedipine oxidase activity (CYP3A4-specific marker reaction), and it was
      also correlated with S-mephenytoin N-demethylase activity (CYP2B6-specific marker
      reaction). Orphenadrine, a specific inhibitor to CYP2B6, and ketoconazole, a
      specific inhibitor to CYP3A4, inhibited the N-demethylation of ketamine in human
      liver microsomes. In human lymphoblast-expressed P450, the activities of CYP2B6
      were higher than those of CYP3A4 and CYP2C9 at three concentrations of ketamine,
      0.005, 0.05, and 0.5 mM. When these results were extrapolated using the average
      relative content of these P450 isoforms in human liver, CYP3A4 was the major
      enzyme involved in ketamine N-demethylation. The present study demonstrates that
      CYP3A4 is the principal enzyme responsible for ketamine N-demethylation in human
      liver microsomes and that CYP2B6 and CYP2C9 have a minor contribution to ketamine
      N-demethylation at therapeutic concentrations of the drug.

PMID- 12065446
TI  - Inflammatory conditions of the male excurrent ductal system. Part I.

PMID- 12065448
TI  - The questionable future of unregulated reproductive medicine.

PMID- 12065447
TI  - Inflammatory conditions of the male excurrent ductal system. Part II.

PMID- 12065449
TI  - A review of the effect of platelet-activating factor on male reproduction and
      sperm function.

PMID- 12065450
TI  - Editorial commentary on Tartagni, et al. Subnormal hypo-osmotic swelling test
      scores as an important cause of cryptic infertility.

PMID- 12065451
TI  - Editorial commentary on Oliva A, et al.

PMID- 12065452
TI  - Editorial commentary on Rochiro, et al.

PMID- 12065454
TI  - DNA replication and germ cell apoptosis during spermatogenesis in the cat.
AB  - Stages at which DNA synthesis and germ cell death take place have recently been
      found to be equivalent in rabbits and rats. Preservation of the timing of these
      processes in different orders of mammals indicates that this timing may be
      crucial for testis cell biology. Since there is no previous study on either germ
      cell proliferation or apoptosis in upper mammals, an analysis of DNA replication
      (by bromodeoxyuridine labeling) and of the location of apoptotic germ cells (by
      the TUNEL assay) has been performed in 3 young adult cats. Our observations
      indicated that in this animal, spermatogonial DNA synthesis occurs at stages V
      (at which point the first generation of replicating spermatogonia appears,
      together with replicating preleptotene spermatocytes), early VII, VIII, and early
      I, II, and IV. Apoptosis of both spermatogonia and spermatocytes was located
      mostly at stages early I, early VI, early VII, and VIII. Interestingly, DNA
      synthesis and germ cell death were found to occur at the same stages of the
      spermatogenic cycle (that is, to occur at the same specific stages of
      development) as those reported for the rabbit and small rodents.

PMID- 12065455
TI  - Cell-cell interactions in the testis of adjuvant-induced arthritic rat.
AB  - Rats with adjuvant-induced arthritis (AA) have low levels of serum testosterone,
      and production of testosterone reportedly is influenced by macrophage secretory
      products. This study was undertaken to understand the mechanism mediating this
      hypoandrogenism. Testicular macrophages from AA and nonarthritic (NA)rats were
      cultured, and conditioned media was added to testicular interstitial cells and
      Percoll-purified cells from NA rats. Testosterone production by interstitial
      cells stimulated with luteinizing hormone (LH) and incubated with adjuvant
      induced arthritic macrophage conditioned medium (AAMCM) was significantly lower
      than in cells incubated with nonarthritic macrophage conditioned medium (NAMCM).
      However, there was no difference in testosterone production by Percoll-purified
      Leydig cells and those stimulated with LH when incubated with AAMCM or NAMCM. To
      determine whether an intermediary cell type was involved in mediating inhibition
      of testosterone production, AAMCM and NAMCM were added to a reconstituted
      preparation of testicular interstitial cells. Addition of AAMCM restored the
      inhibitory effect, suggesting that arthritic hypoandrogenism is mediated by cell
      cell interaction. These results suggest that a factor produced by macrophages
      from AA rats appears to mediate testosterone production by acting in conjunction
      with other cells in the testicular interstitium.

PMID- 12065456
TI  - Usefulness of the hypo-osmotic swelling test in predicting pregnancy rate and
      outcome in couples undergoing intrauterine insemination.
AB  - This study was designed to evaluate the usefulness of the hypo-osmotic swelling
      (HOS) test in predicting successful conception and the pregnancy outcome in
      couples in whom men are affected by mild infertility and fertile women are
      treated with ovulation induction and intrauterine insemination (IUI). We
      retrospectively analyzed the results obtained from 120 couples who underwent not
      more than 3 consecutive cycles of gonadotropin-induced mono-ovulation followed by
      IUI. Semen was analyzed by classical parameters, and the HOS test was performed
      using a hypo-osmotic solution. Using HOS, at least 50% swollen spermatozoa was
      considered normal. The pregnancy rate obtained in couples with an HOS less than
      50% was significantly lower (P <.05) than that achieved in couples with HOS
      values at least 50%. Furthermore, the miscarriage rate was higher when HOS was
      less than 50%. For prediction of successful pregnancy, the sensitivity and
      specificity of the HOS test was 64% and 75%, respectively; the predictive value
      of an abnormal test was 94%, and that of a normal test was 24%. The HOS test may
      detect subtle damage in spermatozoan structure, which is responsible for the
      reduced capacity of spermatozoa to induce a viable embryo, with a low rate of
      pregnancy and a high rate of miscarriage. The results suggest that the HOS test
      may help in recognizing men who have a poor chance of fertilizing their partners
      and to have viable pregnancies using IUI.

PMID- 12065457
TI  - Contraceptive steroids influence the hemostatic activation state in healthy men.
AB  - Hormonal contraception for men requires administration of testosterone and
      gestagens. The effects of a long-acting testosterone ester and 2 different
      progestins on hemostatic activation parameters were studied in relation to
      cardiovascular risk. In phase 1, 7 healthy men aged 28-38 years received a single
      intramuscular injection of 200 mg norethisterone-enanthate (NET-EN) on Day 0.
      Plasma samples were obtained on Days 0, 14, 41, and 84. In phase 2, 3 groups of
      14 healthy men aged 18-45 years received four injections (every 6 weeks) of 1000
      mg testosterone undecanoate (TU), plus daily oral placebo or daily oral
      levonorgestrel (LNG, 250 microg); or four injections (every 6 weeks) of NET-EN.
      Treatment lasted 24 weeks. Plasma samples were obtained at weeks 0, 16, 24, and
      52. All samples were assayed for levels of coagulation factors VIIc, VIIa, XIIc,
      and XIIa; prothrombin fragment F1+2 (F1+2); antithrombin; plasmin-alpha(2)
      antiplasmin-complex (PAP); and fibrinogen. NET-EN alone led to a depletion of
      sexual hormones and a marked shift in hemostatic parameters with increasing
      levels of FXIIc, fibrinogen, antithrombin, and F1+2, whereas FVIIc and FVIIa
      levels decreased. PAP levels increased significantly. Opposite effects were seen
      in the TU/placebo group, with a significant down-regulation of fibrinolysis and
      the hemostatic turnover rate. Testosterone effects were attenuated by additional
      administration of gestagens. The effect of hormonal male contraception using long
      acting testosterone esters with or without gestagens was significantly measurable
      within the hemostatic system. Down-regulation of the hemostatic system with
      testosterone alone may indicate an antithrombotic effect, whereas clinical
      consequences of an additional gestagen compound cannot be derived.

PMID- 12065458
TI  - Binding of protein D/E to the surface of rat epididymal sperm before ejaculation
      and after deposition in the female reproductive tract.
AB  - The objectives of the present investigation were to study the interaction of
      protein D/E with the surface of rat epididymal spermatozoa and to assess its
      topology on the spermatozoa surface before and after deposition in the female
      reproductive tract. Protein D/E, a member of the cysteine-rich secretory protein
      (CRISP-1) family, has been proposed to be involved in sperm-egg membrane fusion.
      In vitro competitive photoactivated cross-linking experiments followed by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis
      revealed that protein D/E molecules specifically interact with two surface
      proteins exhibiting an M(r) approximately 120.0 kd and approximately 130.0 kd,
      respectively, on the sperm surface. In vitro treatment of epididymal spermatozoa
      with phosphatidylinositol specific-phospholipase C revealed the release of
      protein D/E molecules over the head region but not the tail region of
      spermatozoa. Indirect immunofluorescence experiments using polyclonal antibodies
      generated against a highly purified protein D/E preparation demonstrated that
      protein D/E molecules were bound to the surface of spermatozoa recovered from the
      epididymal and female reproductive tracts, even after 7 hours. These results
      indicate that protein D/E molecules interact with specific membrane proteins, and
      is subsequently covalently bound to the surface of spermatozoa via a glycosyl
      phosphatidyl inositol linkage. In addition, protein D/E molecules remain
      covalently bound to spermatozoa after deposition in the female reproductive
      tract, an observation that is consistent with the proposed physiological function
      of the protein in the fertilization process.

PMID- 12065459
TI  - Measurement of volume changes in mouse spermatozoa using an electronic sizing
      analyzer and a flow cytometer: validation and application to an infertile mouse
      model.
AB  - The importance of sperm volume has recently been highlighted in a knockout mouse
      model in which infertility was caused by defects in volume reguiation, which led
      to sperm transport failure in the female tract. Inhibition of volume regulation
      by human sperm, resulting in failure of penetration of cervical mucus in vitro,
      has also been reported. The present work aims to establish a sensitive and
      convenient method for monitoring changes in sperm volume for functional studies.
      Mature murine sperm obtained from the cauda epididymidis were analyzed by flow
      cytometry for their forward and side (90 degrees C) scatter of a 488-nm
      excitation wavelength laser, and the data were compared with volumes measured by
      electronic sizing using a Coulter counter. Changes in cell volume were induced by
      releasing or diluting sperm into culture media of various osmolalities (208-520
      mmol/kg). Forward scatter signal (FSS) intensity correlated well with volume
      measurement obtained by a Coulter counter (R =.83; P <.001), confirming that FSS
      reflects Coulter counter findings as for somatic cells. Sperm swelling was also
      induced by the presence of quinine, a wide-spectrum channel blocker, in a medium
      of 330 mmol/kg, which is similar to the osmolality of uterine fluid. The effect
      of quinine on sperm volume was more obvious when analyzed by flow cytometry than
      by electronic sizing. This effect was even more marked after dead sperm
      identified by fluorescent dye were eliminated from analysis using flow cytometry.
      Swelling was characterized by an increase in forward scatter and side scatter,
      generating a subpopulation of sperm that correlated well (R =.79; P <.0001) with
      the population of sperm exhibiting an angulation of the tail, which is a
      morphological manifestation of swollen murine sperm. Flow cytometric analysis
      revealed that infertile sperm released from the cauda epididymidis of c-ros
      knockout mice were significantly larger than those of fertile sperm from
      heterozygous mice. This finding directly substantiates the suggestion that
      infertile sperm are defective in their volume regulation. Laser scatter analysis
      of viable murine sperm by flow cytometry offers a convenient and sensitive method
      for the study of sperm volume regulation.

PMID- 12065460
TI  - Partial characterization of antigenic sperm proteins in foxes (Vulpes vulpes).
AB  - The aim of this work was to identify antigenic proteins on fox spermatozoa. Fox
      spermatozoa proteins were injected into 3 female rabbits and into 3 male and 3
      female foxes. In rabbits, a rapid humoral response was observed. Using rabbit
      sera for Western blotting, 23 fox sperm protein bands were recognized between 10
      and 110 kd. In foxes, the time course of antibody response was studied in the
      same manner. The number of recognized bands was maximal on day 75 for 2 foxes, on
      day 90 for 3 foxes, and on day 120 for 1 fox. Western blot patterns varied from
      one fox to another. On the whole, 25 protein bands between 10 and 110 kd were
      recognized. Using fluorescein isothiocyanate (FITC) labeling on fox spermatozoa
      with rabbit and fox sera, we showed that several antigens recognized by the
      antisera were located at or near the surface of the spermatozoa. By two
      dimensional electrophoresis and gel-purification, we have selected 6 highly
      antigenic proteins with molecular weights of 11.4, 14.7, 16.4, 16.4, 16.8, and
      16.9 kd, and isoelectric points of 6.0, 6.0, 6.2, 5.5, 5.3, and 5.8,
      respectively, and one antigenic protein at 97 kd with an isoelectric point of 4.3
      to 4.6. The results of this study can be used to characterize these 7 antigens
      selected more precisely by microsequencing or mass spectrometry.

PMID- 12065461
TI  - Development of a cryopreservation protocol for type A spermatogonia.
AB  - The aim of this study was to develop a cryopreservation protocol for type A
      spermatogonia. Testes from 5- to 7-month-old calves were collected, and type A
      spermatogonia were isolated using two-step enzymatic digestion and Percoll
      separation. Cells were resuspended in minimum essential medium (MEM) supplemented
      with 1% bovine serum albumin (BSA) in a final concentration of 6 x 10(6) per mL,
      and the effects of different cryoprotectants and freezing protocols were tested.
      Cells frozen/thawed in medium containing 10% fetal calf serum (FCS) and 1.4 M
      glycerol or dimethyl sulfoxide (DMSO) had a significantly (P <.05) higher
      percentage of living cells compared to medium with only FCS, whereas DMSO gave a
      significantly better cell survival rate than glycerol did. An increase in the
      concentration of FCS in the DMSO-based medium to 20% had no effect on survival
      after freezing and thawing. Furthermore, inclusion of 0.07, 0.14, or 0.21 M
      sucrose in DMSO-based medium resulted in a significant improvement of cell
      survival, cell proliferation in culture, and colonization efficiency in recipient
      testes. A controlled slow-freezing rate (1 degrees C/min) resulted in
      significantly (P <.05) more viable cells than fast (5 degrees C/min) freezing.
      However, noncontrolled-rate freezing, with a comparably low cooling rate, gave
      even better results than the controlled-rate slow freezing. Cryopreservation in
      MEM-based medium containing 10% FCS, 10% DMSO, and 0.07 M sucrose using a non
      controlled-rate freezing protocol appeared to be a simple and effective way to
      preserve type A spermatogonia, with a high yield of almost 70% living cells after
      thawing. Frozen/thawed spermatogonia survived in culture and retained the ability
      to proliferate as determined by colorimetric and bromodeoxyuridine incorporation
      assays. To test whether the stem cells among the A spermatogonia retained their
      ability to colonize the testis of a recipient mouse, bovine spermatogonia were
      transplanted. This resulted in colonization 2-3 months after transplantation. In
      conclusion, for the first time, a method specific for cryopreservation of type A
      spermatogonia, including spermatogonial stem cells was developed, which allows
      long-term preservation of these cells without apparent harmful effects to their
      function.

PMID- 12065462
TI  - Environmental agents and erectile dysfunction: a study in a consulting
      population.
AB  - We evaluated chemical and physical environmental agents as risk factors for
      erectile dysfunction among a consulting population. We studied 199 men who sought
      medical help for erectile disorders between 1996 and 1998 in 3 andrology units in
      the Litoral Sur region of Argentina. Patients were evaluated by monitoring
      nocturnal penile tumescence and rigidity, and were classified as having normal (n
      = 26), irregular (dissociation, short episode or low amplitude, n = 146), or flat
      erectile pattern (n = 26). Exposure to environmental agents was assessed by a
      detailed interview, and 4 groups were constituted: nonexposed, pesticide-exposed,
      solvent-exposed, and heat-exposed. A multivariate polytomous logistic regression
      model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs)
      for association between quality of nocturnal erections and exposure groups
      adjusted for confounding factors. Exposure to environmental agents was a risk
      factor for a flat erectile pattern (OR 7.1, 95% CI 1.5-33.0 for pesticides; OR
      12.2, 95% CI 1.2-124.8 for solvents; and OR 1.7, 95% CI 0.3-9.4 for heat).
      Associations were much weaker for an irregular erectile pattern (OR 1.8, 95% CI
      0.5-6.7 for pesticides; OR 2.1, 95% CI 0.3-17.9 for solvents; and OR 1.2, 95% CI
      0.4-4.0 for heat). Our results suggest that environmental agents constitute a
      risk factor for erectile dysfunction by interfering with erectile ability.

PMID- 12065463
TI  - Cytofluorographic identification of activated T-cell subpopulations in the semen
      of men with spinal cord injuries.
AB  - The semen of most men with spinal cord injury (SCI) contains an abundance of
      leukocytes. It is not known if this leukocytospermia contributes to the
      abnormally low sperm motility observed in many of these men. Our study used flow
      cytometry to identify the leukocyte population in the semen of 12 men with SCI
      compared to 8 healthy age-matched control subjects. The results showed that,
      compared to control subjects, the semen of men with SCI had increased numbers of
      mature granulocytes and lymphocytes. The largest proportion of the leukocytes
      consisted of lymphocytes, and immunophenotypic analysis showed that the greater
      fraction were T cells, many of which coexpressed human leukocyte antigen HLA-DR
      and CD25, suggesting they were in an "activated" state. No significant B-cell
      population was evident. Our finding of immunologically active leukocytes is a
      significant step in understanding the relationship of leukocytospermia and
      decreased sperm motility in the semen of men with SCI.

PMID- 12065464
TI  - Bicarbonate stimulation of boar sperm motility via a protein kinase A-dependent
      pathway: between-cell and between-ejaculate differences are not due to
      deficiencies in protein kinase A activation.
AB  - Because poorly motile sperm samples can often be stimulated by treatments that
      increase intracellular levels of cyclic adenosine monophosphate (cAMP), it has
      been supposed that such samples are unable to maintain an adequate supply of the
      cyclic nucleotide with which to activate protein kinase A (PKA). To investigate
      this hypothesis, we incubated boar sperm samples with bicarbonate (a stimulator
      of adenylyl cyclase) and compared its effect with that of 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole 3',5'-cyclic monophosphothioate (cBIMPS, a highly
      permeable and stable cAMP analog). Videomicroscopy assessment of motility was
      followed by computer analysis of the sperm tracks to produce motility descriptor
      values for many individual cells in each sample, whence "cluster" analysis of
      these data identified groups of spermatozoa that differed in motility
      characteristics. Bicarbonate stimulation of motility was characterized by an
      increase in the linearity (LIN) and progressive velocity of part of the sperm
      population only. The size of this "fast linear" subpopulation varied considerably
      between ejaculates. However, treatment with cBIMPS did not induce significantly
      more "fast linear" sperm than treatment with bicarbonate. In further experiments
      investigating the role of protein kinases in motility control, bicarbonate
      stimulation was greatly inhibited by H89 (a specific inhibitor of PKA), whereas
      GF109203X and lavendustin A (inhibitors of protein kinase C [PKC] and protein
      tyrosine kinase [PTK], respectively) had essentially no effect. While inclusion
      of the protein phosphatase inhibitor calyculin stimulated motility, it failed to
      increase the overall percentage of "fast linear sperm" induced by bicarbonate. We
      conclude that intersperm and interejaculate differences in boar sperm motility
      are not due to inadequacy in cAMP supply or to ineffective PKA activity.

PMID- 12065465
TI  - Effects of sildenafil on nocturnal penile tumescence and rigidity in normal men:
      randomized, placebo-controlled, crossover study.
AB  - We studied the effects of sildenafil on sleep-related erections in 44 adult
      healthy men not affected by erectile dysfunction (mean age +/- SD: 39.3 +/- 10.5
      years). No subjects were administered any medication the first night, but all
      were randomly administered sildenafil 50 mg or placebo the second night and vice
      versa the third night. Sildenafil and placebo were administered 1 hour before
      bedtime. The following parameters of sleep-related erections, after taking
      sildenafil or placebo, were analyzed: total number of valid erections, total
      duration of rigidity more than or equal to 70% of a tightening force of 2.8 N
      applied by the recording device, total duration of increase in penile
      circumference more than or equal to 30 mm, maximum rigidity, mean of maximum
      rigidity, and maximum increase of tumescence. Apart from the maximum increase of
      tumescence, all the parameters analyzed were significantly higher after
      sildenafil than after placebo administration during the first 4 hours of
      monitoring in all subjects (n = 44) (study 1). All the parameters were
      significantly higher after sildenafil than after placebo administration during
      the whole 8 hours of monitoring in 25 of 44 subjects (study 2A) who slept at
      least 8 hours. Comparing both the first and the second 4 hours in the 25 of 44
      subjects who slept at least 8 hours (study 2B), all the parameters were
      significantly higher after sildenafil than after placebo administration, apart
      from maximum rigidity and mean of maximum rigidity during the first 4 hours. Our
      data suggest that sildenafil, administered at bedtime, is efficacious in
      improving sleep-related erections in normal men, indirectly confirming that the
      nitric oxide pathway is crucial in the physiology of erections during sleep. The
      effect of sildenafil is prolonged up to 8-9 hours after its administration.

PMID- 12065466
TI  - Melatonin administration alters semen quality in healthy men.
AB  - The role of melatonin in the regulation of reproduction in humans is unknown. We
      conducted a 6-month, double-blind, crossover study of a daily treatment dose of 3
      mg melatonin or placebo given orally at 1700 hours in 8 healthy men. Semen
      quality (concentration, motility, and morphology), serum and seminal plasma 17
      beta-estradiol (E(2)), testosterone, melatonin, and serum gonadotropin levels
      were determined every 3 months throughout the study. In 6 men, there was no
      change in semen quality or in serum and seminal plasma hormone levels during the
      study period. In 2 men, during the melatonin treatment period, sperm
      concentration decreased to 3 x 10(6)/mL and 12 x 10(6)/mL, and motility declined
      to 32% and 30%. These coincided with a decline in seminal plasma and serum E(2)
      levels and with an increase in testosterone:E(2) ratios. Six months after the
      cessation of melatonin, sperm concentration and motility were normal in 1 man but
      remained abnormal in the other one with a still elevated testosterone:E(2) ratio.
      Serum gonadotropin levels were unchanged during the study in all 8 men. Our
      preliminary observations suggest that long-term melatonin administration is
      associated with decreased semen quality in a number of healthy men, probably
      through the inhibition of aromatase at the testicular level.

PMID- 12065468
TI  - DNA immunization in a mouse model of latent tuberculosis: effect of DNA
      vaccination on reactivation of disease and on reinfection with a secondary
      challenge.
AB  - Individuals who are latently infected with Mycobacterium tuberculosis can develop
      active disease via either endogenous reactivation of the latent bacilli or
      exogenous reinfection with a second mycobacterial strain. In this study, we
      investigated whether immunization with a tuberculosis DNA vaccine cocktail that
      induces significant protective responses in mice could prevent reactivation of
      disease in a murine latent-tuberculosis model. In addition, we assessed whether
      DNA vaccination could retard the growth of a secondary aerogenic infection with
      M. tuberculosis (exogenous reinfection) in latently infected mice. In the
      reactivation studies, administration of the DNA vaccine combination did not
      prevent recrudescence of the latent infection after injection of dexamethasone.
      Moreover, for the reinfection experiments, only a modest decrease in the growth
      of a secondary M. tuberculosis challenge in DNA-vaccinated animals, compared to
      controls, was observed 14 and 28 days after the reinfection of previously exposed
      mice. Interestingly, although proliferation of the secondary challenge was
      reduced significantly in a nonvaccinated chronic-infection group relative to the
      naive controls, the number of bacilli still increased by 500-fold 1 month after
      the secondary challenge in mice with active tuberculosis. These results indicate
      that novel immunotherapeutic approaches will be required to prevent reactivation
      of infection or reinfection of individuals with latent tuberculosis.

PMID- 12065467
TI  - Host-pathogen interactions: subversion and utilization of the NF-kappa B pathway
      during infection.

PMID- 12065469
TI  - Protection of mice against brucellosis by intranasal immunization with Brucella
      melitensis lipopolysaccharide as a noncovalent complex with Neisseria
      meningitidis group B outer membrane protein.
AB  - Intranasal immunization of mice with purified Brucella melitensis
      lipopolysaccharide (LPS) as a noncovalent complex with Neisseria meningitidis
      group B outer membrane protein (GBOMP) elicited a high-titer anti-LPS systemic
      antibody response and a significant mucosal antibody response. The anti-LPS
      immunoglobulin G (IgG) antibody was predominantly of the IgG1 subtype, although
      there was some response of the IgG2a, IgG2b, and IgG3 subtypes. The antibody
      titer remained high for 16 weeks postimmunization. Immunized mice and sham
      immunized control mice were challenged intranasally with 10(4) CFU of virulent B.
      melitensis strain 16 M 4 weeks after the second dose of vaccine. The numbers of
      bacteria in lungs, livers, and spleens at 3 days, 9 days, and 8 weeks
      postchallenge were determined. Bacteria were found in lungs of all mice on day 3,
      but there was no disseminated infection of liver or spleen. By day 9, 40% of the
      mice had infected spleens and livers. At 8 weeks postchallenge, spleens of 25 of
      62 immunized mice were infected, compared to 61 of 62 control mice (P < 0.0001).
      The livers of 12 of 43 immunized mice were infected, compared to 22 of 36 control
      mice (P = 0.005). In contrast, the lungs of 26 of 46 immunized mice were still
      infected, compared to 27 of 44 control mice. The numbers of bacterial CFU in
      lungs of immunized and control animals were identical. These studies show that
      intranasal immunization with B. melitensis LPS-GBOMP subunit vaccine
      significantly protects mice against intranasal challenge with virulent B.
      melitensis. Vaccination reduces bacterial dissemination to spleen and liver but
      has no effect on the course of lung infection.

PMID- 12065470
TI  - Localization within a proline-rich antigen (Ag2/PRA) of protective antigenicity
      against infection with Coccidioides immitis in mice.
AB  - Subunits of a proline-rich coccidioidal antigen (Ag2/PRA) of Coccidioides immitis
      were analyzed by comparison as vaccines in mice. The optimal dose of plasmid
      vaccine encoding full-length Ag2/PRA was determined to be between 10 and 100
      microg. Mice vaccinated with plasmids encoding amino acids (aa) 1 to 106 were as
      protective as full-length Ag2/PRA (aa 1 to 194). The subunit from aa 27 to 106
      was significantly but less protective. Plasmids encoding aa 90 to 151 or aa 90 to
      194 were not protective. Analogous results were obtained with recombinant
      vaccines of the same amino acid sequences. In addition, mixtures of aa 90 to 194
      with either aa 1 to 106 or aa 27 to 106 did not enhance protection compared to
      the active single-recombinant subunits alone. Humoral response of total
      immunoglobulin G (IgG) and subclasses IgG1 and IgG2a were detectable in subunit
      vaccinations but at significantly (100-fold) lower concentrations than after
      vaccination with plasmids encoding full-length Ag2/PRA. Since virtually all
      protection by vaccination with full-length Ag2/PRA can be accounted for in the
      first half of the protein (aa 1 to 106), this subunit could make a multicomponent
      vaccine more feasible by reducing the quantity of protein per dose and the
      possibility of an untoward reactions to a foreign protein.

PMID- 12065471
TI  - Identification of Chlamydia pneumoniae-derived mouse CD8 epitopes.
AB  - Chlamydia pneumoniae is a common intracellular human pathogen that has been
      associated with several severe pathological conditions, including coronary heart
      disease and atherosclerosis. There is no vaccine against C. pneumoniae infection,
      but CD8(+) T cells have been shown to be crucial for protection during
      experimental infection. However, the effector functions and epitope specificity
      of the protective CD8(+) T cell remain unknown. The aim of this study was to
      identify C. pneumoniae-derived mouse CD8 epitopes by using a recent epitope
      prediction method. Of four C. pneumoniae proteins (the major outer membrane
      protein, outer membrane protein 2, polymorphic outer membrane protein 5, and heat
      shock protein 60), 53 potential CD8(+) T-cell epitopes were predicted by H-2
      class I binding algorithms. Nineteen of the 53 peptides were identified as CD8
      epitopes by testing for induction of a cytotoxic response after immunization. To
      test whether the predicted epitopes are naturally processed and presented by C.
      pneumoniae-infected cells, we generated a panel of seven peptide-specific
      cytotoxic T lymphocyte lines that were subsequently tested for recognition of C.
      pneumoniae-infected target cells. By using this strategy, we were able to
      identify three C. pneumoniae CD8 epitopes that were, indeed, processed and
      presented on infected cells. Identification of these natural CD8 epitopes
      provides tools for characterization of CD8(+) T-cell function in vivo and
      generation of epitope-specific prevention strategies.

PMID- 12065472
TI  - Assessment of virulence of uropathogenic Escherichia coli type 1 fimbrial mutants
      in which the invertible element is phase-locked on or off.
AB  - Type 1 fimbria is a proven virulence factor of uropathogenic Escherichia coli
      (UPEC), causing urinary tract infections. Expression of the fimbria is regulated
      at the transcriptional level by a promoter situated on an invertible element,
      which can exist in one of two different orientations. The orientation of the
      invertible element that allows the expression of type 1 fimbriae is defined as
      "on," and the opposite orientation, in which no transcription occurs, is defined
      as "off." During the course of a urinary tract infection, we have observed that
      the infecting E. coli population alternates between fimbriated and nonfimbriated
      states, with the fimbriated on orientation peaking at 24 h. We propose that the
      ability of the invertible element to switch orientations during infection is
      itself a virulence trait. To test this hypothesis, nucleotide sequence changes
      were introduced in the left inverted repeat of the invertible element of UPEC
      pyelonephritis strain CFT073 that locked the invertible elements permanently in
      either the on or the off orientation. The virulence of these mutants was assessed
      in the CBA mouse model of ascending urinary tract infection at 4, 24, 48, and 72
      h postinoculation (hpi). We conducted independent challenges, in which bladders
      of mice were inoculated with either a single mutant or the wild type, and
      cochallenges, in which a mutant and the wild type were inoculated together to
      allow direct competition in the urinary tract. In both sets of experimental
      infections, the locked-off mutant was recovered from the urine, bladder, and
      kidneys in significantly lower numbers than the wild type at 24 hpi (P < or =
      0.05), demonstrating its attenuation. Conversely, the locked-on mutant was
      recovered in higher numbers than the wild type at 24 hpi (P < or = 0.05), showing
      enhanced virulence of this mutant. No significant differences were seen between
      the mutants and wild type in the urine or the bladder at 48 or 72 hpi. However,
      the wild type outcompeted the locked-off mutant in the kidneys during the
      cochallenge experiment at 72 hpi (P = 0.009). Overall, these data suggest that
      the ability of the invertible element controlling type 1 fimbria expression to
      phase vary contributes significantly to virulence early (24 hpi) in the course of
      a urinary tract infection by UPEC and most profoundly influences colonization of
      the bladder.

PMID- 12065473
TI  - Protective immunity conferred by attenuated aroA derivatives of Pasteurella
      multocida B:2 strains in a mouse model of hemorrhagic septicemia.
AB  - Hemorrhagic septicemia (HS) is a fatal systemic disease of cattle and buffaloes.
      In South Asia HS is caused by infection with Pasteurella multocida serotype B:2.
      Some control is achieved with alum-precipitated or oil-adjuvanted killed whole
      cell vaccines injected subcutaneously, but these vaccines provide only short-term
      immunity and require annual administration for effective use. Live attenuated
      vaccines have the advantage of a natural route of entry into the host, but for
      live strains to be used as vaccines, the mode of attenuation should be well
      defined. We constructed aroA attenuated derivatives of two P. multocida serotype
      B:2 strains by allelic exchange of the native aroA sequence with aroA sequences
      disrupted with a kanamycin resistance cassette or with marker-free aroA sequences
      containing an internal deletion. These strains were confirmed to be aroA mutants
      by PCR and Southern blot analysis, enzyme assay, and lack of growth on minimal
      medium. The aroA derivatives were highly attenuated for virulence in a mouse
      model of HS. Mouse challenge experiments showed that intraperitoneal or
      intranasal vaccination of an aroA strain completely protected mice against
      challenge with a high dose (>1,000 50% lethal doses) of either the parent strain
      or the other wild-type B:2 strain. The spread of the parent and the aroA
      derivatives to different organs was compared when the organisms were inoculated
      by different routes.

PMID- 12065474
TI  - Modulation of C5aR expression on human neutrophils by encapsulated and acapsular
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans and cryptococcal surface polysaccharides influenced C5aR
      expression on human polymorphonuclear neutrophils (PMN). Encapsulated and
      acapsular strains produced dramatically different effects. Treatment of PMN with
      acapsular cryptococci up-regulated C5aR expression; whereas treatment with
      encapsulated cells suppressed C5aR expression. Glucuronoxylomannan (GXM), the
      principal constituent of the cryptococcal capsule, was responsible for such
      inhibition. Increased C5aR expression following treatment with acapsular
      cryptococci was accompanied by increased binding of C5a to PMN, increased
      superoxide production in response to stimulation with C5a, and an increased
      chemotactic response to C5a. Conversely, decreased C5aR expression following
      treatment with encapsulated cryptococci or acapsular cryptococci that had been
      pretreated with GXM was accompanied by decreased binding of C5a to PMN and a
      decreased chemotactic response to C5a. Our results raise the possibility that the
      down-regulation of C5aR expression by encapsulated cryptococci might alter PMN
      function at the site of cryptococcal infection.

PMID- 12065475
TI  - ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron
      dependent gene expression, iron metabolism, and oxidative stress response.
AB  - The mycobacterial IdeR protein is a metal-dependent regulator of the DtxR
      (diphtheria toxin repressor) family. In the presence of iron, it binds to a
      specific DNA sequence in the promoter regions of the genes that it regulates,
      thus controlling their transcription. In this study, we provide evidence that
      ideR is an essential gene in Mycobacterium tuberculosis. ideR cannot normally be
      disrupted in this mycobacterium in the absence of a second functional copy of the
      gene. However, a rare ideR mutant was obtained in which the lethal effects of
      ideR inactivation were alleviated by a second-site suppressor mutation and which
      exhibited restricted iron assimilation capacity. Studies of this strain and a
      derivative in which IdeR expression was restored allowed us to identify
      phenotypic effects resulting from ideR inactivation. Using DNA microarrays, the
      iron-dependent transcriptional profiles of the wild-type, ideR mutant, and ideR
      complemented mutant strains were analyzed, and the genes regulated by iron and
      IdeR were identified. These genes encode a variety of proteins, including
      putative transporters, proteins involved in siderophore synthesis and iron
      storage, members of the PE/PPE family, a membrane protein involved in virulence,
      transcriptional regulators, and enzymes involved in lipid metabolism.

PMID- 12065476
TI  - Borrelia burgdorferi population kinetics and selected gene expression at the host
      vector interface.
AB  - By using real-time quantitative PCR, the population dynamics and gene
      transcription of Borrelia burgdorferi were examined in ticks and skin of mice
      during acquisition of the infection from mice by ticks and during transmission of
      the infection from ticks to mice. Population dynamics were determined by using a
      flaB DNA target. A quantitative analysis of flaB, ospA, ospC, dbpA, and arp
      transcription was also performed. The results revealed that both uninfected
      larval and nymphal Ixodes scapularis ticks acquired B. burgdorferi as early as 1
      day after attachment and that the sizes of spirochete populations within ticks
      increased during feeding. In addition, all gene targets revealed that there was
      RNA transcription during feeding. Similar events occurred within infected nymphal
      ticks feeding on uninfected hosts. Transmission from infected nymphal ticks to
      mice could be detected within 1 day after attachment. Analysis of skin during the
      first 3 days after attachment of infected ticks revealed rising numbers of
      spirochetes but minimal gene transcription. In contrast, the skin of mice with
      established infections revealed static populations of spirochetes and active but
      stable transcription of flaB, ospC, dbpA, and arp. There were consistent
      reductions in the number of spirochetes in the skin at the tick attachment sites
      compared to the number of spirochetes in the skin at nontick sites, but there
      were no differences in gene expression between tick and nontick skin sites.
      Evidence of ospA transcription in skin could be found 1 day after tick attachment
      but not thereafter.

PMID- 12065477
TI  - Overproduction of type 8 capsular polysaccharide augments Staphylococcus aureus
      virulence.
AB  - Type 8 capsular polysaccharide (CP8) is the most prevalent capsule type in
      clinical isolates of Staphylococcus aureus. However, its role in virulence has
      not been clearly defined. CP8 strains such as strain Becker produce a small
      amount of capsule on their surface in vitro. In contrast, CP1 strains such as
      strain M produce a large amount of capsule, which has been shown to be an
      important antiphagocytic virulence factor. The cap8 and cap1 operons, required
      for the synthesis of CP8 and CP1, respectively, have been cloned and sequenced.
      To test whether CP8 contributes to the pathogenesis of S. aureus, we replaced the
      weak native promoter of the cap8 operon in strain Becker with the strong
      constitutive promoter of the cap1 operon of strain M. The resultant strain,
      CYL770, synthesized cap8-specific mRNA at a level about sevenfold higher than
      that in the parent strain. Remarkably, the CYL770 strain produced about 80-fold
      more CP8. In a mouse infection model of bacteremia, the CP8-overproducing strain
      persisted longer in the bloodstream, the liver, and the spleen in mice than the
      parent strain. In addition, strain CYL770 was more resistant to
      ospsonophagocytosis in vitro by human polymorphonuclear leukocytes. These results
      indicate that CP8 is an antiphagocytic virulence factor of S. aureus.

PMID- 12065478
TI  - Proteome analysis of secreted proteins of the gastric pathogen Helicobacter
      pylori.
AB  - Secreted proteins (the secretome) of the human pathogen Helicobacter pylori may
      mediate important pathogen-host interactions, but such proteins are technically
      difficult to analyze. Here, we report on a comprehensive secretome analysis that
      uses protein-free culture conditions to minimize autolysis, an efficient recovery
      method for extracellular proteins, and two-dimensional gel electrophoresis
      followed by peptide mass fingerprinting for protein resolution and
      identification. Twenty-six of the 33 separated secreted proteins were identified.
      Among them were six putative oxidoreductases that may be involved in the
      modification of protein-disulfide bonds, three flagellar proteins, three defined
      fragments of the vacuolating toxin VacA, the serine protease HtrA, and eight
      proteins of unknown function. A cleavage site for the amino-terminal passenger
      domain of VacA between amino acids 991 and 992 was determined by collision
      induced dissociation mass spectrometry. Several of the secreted proteins are
      interesting targets for antimicrobial chemotherapy and vaccine development.

PMID- 12065479
TI  - Identification of Escherichia coli genes that are specifically expressed in a
      murine model of septicemic infection.
AB  - Identification and characterization of bacterial genes that are induced during
      the disease process are important in understanding the molecular mechanism of
      disease and can be useful in designing antimicrobial drugs to control the
      disease. The identification of in vivo induced (ivi) genes of an Escherichia coli
      septicemia strain by using antibiotic-based in vivo expression technology is
      described. Bacterial clones resistant to chloramphenicol in vivo were recovered
      from the livers of infected mice. Most of the ivi clones were sensitive to
      chloramphenicol when grown in vitro. Using reverse transcription-PCR, it was
      demonstrated that selected ivi clones expressed cat in the livers of infected
      mice but not during in vitro growth. A total of 750 colonies were recovered after
      three successive rounds of in vivo selection, and 168 isolated ivi clones were
      sequenced. The sequence analysis revealed that 37 clones encoded hypothetical
      proteins found in E. coli K-12, whereas 10 clones contained genes that had no
      significant homology to DNA sequences in GenBank. Two clones were found to
      contain transposon-related functions. Other clones contained genes required for
      amino acid metabolism, anaerobic respiration, DNA repair, the heat shock
      response, and the cellular repressor of the SOS response. In addition, one clone
      contained the aerobactin biosynthesis gene iucA. Mutations were introduced in to
      seven of the identified ivi genes. An in vivo mouse challenge-competition assay
      was used to determine if the mutants were attenuated. The results suggested that
      these ivi genes were important for survival in vivo, and three of the seven
      mutant ivi clones were required for successful infection of mice.

PMID- 12065480
TI  - Protein disulfide isomerase, a component of the estrogen receptor complex, is
      associated with Chlamydia trachomatis serovar E attached to human endometrial
      epithelial cells.
AB  - Chlamydia trachomatis serovar E, the leading bacterial agent responsible for
      sexually transmitted diseases, is required to invade genital epithelial cells for
      its growth and survival, yet little is known about the adhesin-receptor
      interactions promoting its entry. In contrast, much has been published on the
      heparan sulfate receptor for binding C. trachomatis L2 elementary bodies (EBs)
      prior to entry into HeLa cells. Using a different experimental approach in which
      a biotinylated apical membrane protein receptor(s) attached to EB at 4 degrees C
      was stripped off the surface of polarized HEC-1B cells and immunoprecipitated
      with polyclonal anti-EB antibodies, an approximately 55-kDa protein was
      reproducibly detected by enhanced chemiluminescence and two-dimensional gel
      electrophoresis. Matrix-assisted laser desorption ionization mass-spectrometry
      sequence analysis revealed the 55-kDa protein to be protein disulfide isomerase
      (PDI), a member of the estrogen receptor complex which carries out thiol
      disulfide exchange reactions at infected host cell surfaces. Exposure of HEC-1B
      cells during EB attachment (1.5 to 2 h) to three different inhibitors of PDI
      reductive reactions--(i) the thiol-alkylating reagent DTNB (5,5'-dithiobis[2
      nitrobenzoic acid]), (ii) bacitracin, and (iii) anti-PDI antibodies--resulted in
      reduced chlamydial infectivity. Since (i) C. trachomatis serovar E attachment to
      estrogen-dominant primary human endometrial epithelial cells is dramatically
      enhanced and (ii) productive entry into and infectivity of EB in host cells is
      dependent on reduction of EB cross-linked outer membrane proteins at the host
      cell surface, these data provide some preliminary evidence for an intriguing new
      potential receptor candidate for further analysis of luminal C. trachomatis
      serovar E entry.

PMID- 12065482
TI  - Identification of a receptor-binding domain of Bordetella dermonecrotic toxin.
AB  - Bordetella dermonecrotic toxin (DNT) stimulates the assembly of actin stress
      fibers and focal adhesions by deamidating or polyaminating Gln63 of the small
      GTPase Rho. DNT is an A-B toxin which is composed of an N-terminal receptor
      binding (B) domain and a C-terminal enzymatically active (A) domain. In this
      study, to analyze the functional and structural organization of DNT, we prepared
      10 clones of hybridoma producing anti-DNT monoclonal antibodies. One of these
      antibodies, 2B3, neutralized the effects of DNT on target cells when mixed with
      the toxin. When microinjected into cells, however, 2B3 did not inhibit the
      intoxication by DNT. Western blot analysis revealed that 2B3 recognized the N
      terminal region of DNT. To delineate the DNT-binding domain, we examined a series
      of truncated DNT mutants for the ability to competitively inhibit the
      intoxication of cells by the full-length DNT and found that a fragment consisting
      of the N-terminal 54 amino acids (DNT(1-54)) was the smallest inhibitory
      fragment. The radioiodinated DNT(1-54) actually bound to target cells, which was
      inhibited by 2B3. These results suggest that the N-terminal 54 amino acids of DNT
      are responsible for the binding to target cells. DNT(1-54) bound to none of the
      DNT-resistant cells, implying the presence of a cell surface receptor specific to
      DNT-sensitive cells.

PMID- 12065481
TI  - Identification of the Vibrio cholerae enterobactin receptors VctA and IrgA: IrgA
      is not required for virulence.
AB  - The gram-negative enteric pathogen Vibrio cholerae requires iron for growth. V.
      cholerae has multiple iron acquisition systems, including utilization of heme and
      hemoglobin, synthesis and transport of the catechol siderophore vibriobactin, and
      transport of several siderophores that it does not itself make. One siderophore
      that V. cholerae transports, but does not make, is enterobactin. Enterobactin
      transport requires TonB and is independent of the vibriobactin receptor ViuA. In
      this study, two candidate enterobactin receptor genes, irgA (VC0475) and vctA
      (VCA0232), were identified by analysis of the V. cholerae genomic sequence. A
      single mutation in either of these genes did not significantly impair
      enterobactin utilization, but a strain defective in both genes did not use
      enterobactin. When either irgA or vctA was supplied on a plasmid, the ability of
      the irgA vctA double mutant to use enterobactin was restored. This indicates that
      both VctA and IrgA transport enterobactin. We also identify the genes vctPDGC,
      which are linked to vctA and encode a periplasmic binding protein-dependent ABC
      transport system that functions in the utilization of both enterobactin and
      vibriobactin (VCA0227-0230). An irgA::TnphoA mutant strain, MBG40, was shown in a
      previous study to be highly attenuated and to have a strong colonization defect
      in an infant mouse model of V. cholerae infection (M. B. Goldberg, V. J. DiRita,
      and S. B. Calderwood, Infect. Immun. 58:55-60, 1990). In this work, a new irgA
      mutation was constructed, and this mutant strain was not significantly impaired
      in its ability to compete with the parental strain in infant mice and was not
      attenuated for virulence in an assay of 50% lethal dose. These data indicate that
      the virulence defect in MBG40 is not due to the loss of irgA function and that
      irgA is unlikely to be an important virulence factor.

PMID- 12065483
TI  - Role of toll-like receptors in changes in gene expression and NF-kappa B
      activation in mouse hepatocytes stimulated with lipopolysaccharide.
AB  - The liver is an important site of host-microbe interaction. Although hepatocytes
      have been reported to be responsive to lipopolysaccharide (LPS), the global gene
      expression changes by LPS and mechanism(s) by which LPS stimulates cultured
      hepatocytes remain uncertain. Cultures of primary mouse hepatocytes were
      incubated with LPS to assess its effects on the global gene expression, hepatic
      transcription factors, and mitogen-activated protein (MAP) kinase activation. DNA
      microarray analysis indicated that LPS modulates the selective expression of more
      than 80 genes and expressed sequence tags. We have shown previously that
      hepatocytes express CD14, which is required both for uptake and responsiveness to
      LPS. In other cells, responsiveness to microbial products requires expression of
      Toll-like receptors (TLR) and their associated accessory molecules. Hepatocytes
      expressed TLR1 through TLR9 as well as MyD88 and MD-2 transcripts, as shown by
      reverse transcriptase PCR analysis, indicating that hepatocytes express all known
      microbe recognition molecules. The MAP kinase extracellular signal-regulated
      kinase 1/2 was phosphorylated in response to LPS in mouse hepatocytes, and the
      levels of phosphorylation were lower in hepatocytes from TLR4-null mice. NF-kappa
      B activation was reduced in TLR4-mutant or -null hepatocytes compared to control
      hepatocytes, and this defect was partially restored by adenoviral transduction of
      mouse TLR4. Thus, hepatocytes respond to nanogram concentrations of LPS through a
      TLR4 response pathway.

PMID- 12065484
TI  - A parasitic phase-specific adhesin of Coccidioides immitis contributes to the
      virulence of this respiratory Fungal pathogen.
AB  - We report the isolation of a Coccidioides immitis gene (SOWgp) which encodes an
      immunodominant, spherule outer wall glycoprotein that is presented as a component
      of a parasitic phase-specific, membranous layer at the cell surface. The open
      reading frame of the gene from C. immitis isolate C735 translates a 422-amino
      acid (aa) polypeptide that contains 6 copies of a 41- to 47-residue tandem repeat
      enriched in proline (20.4 mol%) and aspartate (19.7%). Two additional isolates of
      C. immitis produce SOWgps of different molecular sizes (328 and 375 aa) and show
      a corresponding difference in the number of tandem repeats (four and five,
      respectively). The accurate molecular sizes of these proline-rich antigens, as
      determined by surface-enhanced laser desorption/ionization mass spectrometry, are
      comparable to the predicted sizes from the translated protein sequences rather
      than the estimated sizes based on gel-electrophoretic separation. The results of
      Northern hybridization confirmed that SOWgp expression is parasitic phase
      specific, and immunoblot studies showed that elevated levels of production of
      this antigen occurred during early spherule development. The recombinant
      polypeptide (rSOWp) was shown to bind to mammalian extracellular matrix (ECM)
      proteins in an in vitro assay (laminin > fibronectin > collagen type IV),
      suggesting that the parasitic cell surface antigen may function as an adhesin.
      Deletion of the SOWgp gene by using a targeted gene replacement strategy resulted
      in partial loss of the ability of intact spherules to bind to ECM proteins and a
      significant reduction in virulence of the mutant strain. The wild-type gene was
      restored in the mutant by homologous recombination, and the revertant strain was
      shown to be as virulent as the parental isolate in our murine model of
      coccidioidomycosis. The parasitic cell surface glycoprotein encoded by the SOWgp
      gene appears to function as an adhesin and contributes to the virulence of C.
      immitis.

PMID- 12065485
TI  - Characterization of Salmonella enterica derivatives harboring defined aroC and
      Salmonella pathogenicity island 2 type III secretion system (ssaV) mutations by
      immunization of healthy volunteers.
AB  - The attenuation and immunogenicity of two novel Salmonella vaccine strains,
      Salmonella enterica serovar Typhi (Ty2 Delta aroC Delta ssaV, designated ZH9) and
      S. enterica serovar Typhimurium (TML Delta aroC Delta ssaV, designated WT05),
      were evaluated after their oral administration to volunteers as single escalating
      doses of 10(7), 10(8), or 10(9) CFU. ZH9 was well tolerated, not detected in
      blood, nor persistently excreted in stool. Six of nine volunteers elicited anti
      serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting
      cell (ASC) responses, with three of three vaccinees receiving 10(8) and two of
      three receiving 10(9) CFU which elicited high-titer LPS-specific serum IgG. WT05
      was also well tolerated with no diarrhea, although the administration of 10(8)
      and 10(9) CFU resulted in shedding in stools for up to 23 days. Only volunteers
      immunized with 10(9) CFU of WT05 mounted detectable serovar Typhimurium LPS
      specific ASC responses and serum antibody responses were variable. These data
      indicate that mutations in type III secretion systems may provide a route to the
      development of live vaccines in humans and highlight significant differences in
      the potential use of serovars Typhimurium and Typhi.

PMID- 12065486
TI  - Changes in temporal and spatial patterns of outer surface lipoprotein expression
      generate population heterogeneity and antigenic diversity in the Lyme disease
      spirochete, Borrelia burgdorferi.
AB  - Borrelia burgdorferi differentially expresses many of the OspE/F/Elp paralogs
      during tick feeding. These findings, combined with the recent report that stable
      B. burgdorferi infection of mammals occurs only after 53 h of tick attachment,
      prompted us to further analyze the expression of the OspE/F/Elp paralogs during
      this critical period of transmission. Indirect immunofluorescence analysis
      revealed that OspE, p21, ElpB1, ElpB2, and OspF/BbK2.11 are expressed in the
      salivary glands of ticks allowed to feed on mice for 53 to 58 h. Interestingly,
      many of the spirochetes in the salivary glands that expressed abundant amounts of
      these antigens were negative for OspA and OspC. Although prior reports have
      indicated that OspE/F/Elp orthologs are surface exposed, none of the individual
      lipoproteins or combinations of the lipoproteins protected mice from challenge
      infections. To examine why these apparently surface-exposed lipoproteins were not
      protective, we analyzed their genetic stability during infection and their
      cellular locations after cultivation in vitro and within dialysis membrane
      chambers, mimicking a mammalian host-adapted state. Combined restriction fragment
      length polymorphism and nucleotide sequence analyses revealed that the genes
      encoding these lipoproteins are stable for at least 8 months postinfection.
      Interestingly, cellular localization experiments revealed that while all of these
      proteins can be surface localized, there were significant populations of
      spirochetes that expressed these lipoproteins only in the periplasm. Furthermore,
      host-specific signals were found to alter the expression patterns and final
      cellular location of these lipoproteins. The combined data revealed a remarkable
      heterogeneity in populations of B. burgdorferi during tick transmission and
      mammalian infection. The diversity is generated not only by temporal changes in
      antigen expression but also by modulation of the surface lipoproteins during
      infection. The ability to regulate the temporal and spatial expression patterns
      of lipoproteins throughout infection likely contributes to persistent infection
      of mammals by B. burgdorferi.

PMID- 12065487
TI  - Plasmodium vivax promiscuous T-helper epitopes defined and evaluated as linear
      peptide chimera immunogens.
AB  - Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell
      epitopes are required to elicit consistent and long-lasting immune responses. We
      report here the identification and functional characterization of six T-cell
      epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax
      (PvMSP-1) and bind promiscuously to four different HLA-DRB1* alleles. Each of
      these peptides induced lymphoproliferative responses in cells from individuals
      with previous P. vivax infections. Furthermore, linear-peptide chimeras
      containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with
      the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell
      epitope, induced high specific antibody titers, cytokine production, long-lasting
      immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A
      linear-peptide chimera containing an allele-restricted P. falciparum T-cell
      epitope with the CSP B-cell epitope was not effective. Two out of the six
      promiscuous T-cell epitopes exhibiting the highest anti-peptide response also
      contain B-cell epitopes. Antisera generated against these B-cell epitopes
      recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti
      peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of
      P. falciparum sporozoites into human hepatocytes. These data and the simplicity
      of design of the chimeric constructs highlight the potential of multimeric,
      multistage, and multispecies linear-peptide chimeras containing parasite
      promiscuous T-cell epitopes for malaria vaccine development.

PMID- 12065488
TI  - Persistence of protective immunity to malaria induced by DNA priming and poxvirus
      boosting: characterization of effector and memory CD8(+)-T-cell populations.
AB  - The persistence of immunity to malaria induced in mice by a heterologous DNA
      priming and poxvirus boosting regimen was characterized. Mice were immunized by
      priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite
      protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and
      boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with
      either high-dose (100 microg of p PyCSP plus 30 microg of pGM-CSF) or low-dose (1
      microg of p PyCSP plus 1 microg of pGM-CSF DNA) priming were protected against
      challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization
      was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30
      to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still
      protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector
      CD8(+)-T-cell population present 2 weeks after boosting had ex vivo Ag-specific
      cytolytic activity, expressed both gamma interferon (IFN-gamma) and tumor
      necrosis factor alpha, and constituted 12 to 20% of splenic CD8(+) T cells. In
      contrast, the memory CD8(+)-Ag-specific-cell population at 28 weeks lacked
      cytolytic activity and constituted only 6% of splenic CD8(+) T cells, but at the
      single-cell level it produced significantly higher levels of IFN-gamma than the
      effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks
      after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was
      similarly immunogenic and as protective as high-dose priming against a 50-, but
      not a 250-, sporozoite challenge. These results demonstrate that a heterologous
      priming and boosting vaccination can provide lasting protection against malaria
      in this model system.

PMID- 12065489
TI  - Bicarbonate ion stimulates the expression of locus of enterocyte effacement
      encoded genes in enterohemorrhagic Escherichia coli O157:H7.
AB  - Enterohemorrhagic Escherichia coli (EHEC) strains adhere to the intestinal mucosa
      and produce an attaching and effacing (A/E) lesion. Most of the genes required to
      produce A/E lesions are thought to be encoded by the 36-kb pathogenicity island
      termed the locus for enterocyte effacement (LEE). Although the mechanisms
      underlying the bacterial adherence, including the genes involved, are still
      poorly understood, the preferential adherence phenotype of EHEC is thought to
      depend on the nature of the genes and/or the response of these genes to changes
      in environmental conditions. To explore the environmental factors affecting EHEC
      adherence, we used an O157:H7 strain and investigated the optimal growth
      conditions for its adherence to Caco-2 cells. We observed that EHEC grown in
      Dulbecco's modified Eagle's medium (DMEM) adhered more efficiently to Caco-2
      cells than EHEC grown in Luria-Bertani (LB) broth. Among the components of DMEM,
      only NaHCO(3) was found to remarkably stimulate bacterial adherence. When
      bacteria were grown in LB broth containing NaHCO(3), the production of intimin,
      Tir, EspA, and EspB was greatly enhanced compared with the production in LB
      broth. Indeed, the transcription of ler required for LEE-encoded gene expression
      was promoted in response to the concentration of NaHCO(3) in LB broth. Since the
      concentration of NaHCO(3) in the lower intestinal tract has been shown to be
      relatively high compared with that in the upper small intestine, our results may
      imply that NaHCO(3) is an important signaling factor for promoting colonization
      of EHEC in the lower intestinal tract in humans.

PMID- 12065490
TI  - Effect of low- and high-virulence Yersinia enterocolitica strains on the
      inflammatory response of human umbilical vein endothelial cells.
AB  - Pathogenic strains of Yersinia spp. inject a set of Yop effector proteins into
      eukaryotic cells by using a plasmid-encoded type III secretion system. In this
      study, we analyzed the inflammatory response of human umbilical vein endothelial
      cells (HUVECs) after infection with different Yersinia enterocolitica strains. We
      found that both expression of intercellular adhesion molecule 1 and release of
      the cytokines interleukin-6 (IL-6) and IL-8 by HUVECs are downregulated in a YopP
      dependent way, demonstrating that YopP plays a major role in the inflammatory
      response of these cells. Infection of HUVECs with several low-virulence (biotype
      2, 3, and 4) and high-virulence (biotype 1B) Y. enterocolitica strains showed
      that biotype 1B isolates are more efficient in inhibiting the inflammatory
      response than low-virulence Y. enterocolitica strains and that this effect
      depends on the time of contact. We extended the results of Ruckdeschel et al. and
      found that on the basis of the presence or absence of arginine-143 of YopP (K.
      Ruckdeschel, K. Richter, O. Mannel, and J. Heesemann, Infect. Immun. 69:7652
      7662, 2001) all the Y. enterocolitica strains used fell into two groups, which
      correlate with the low- and high-virulence phenotypes. In addition, we found that
      high-virulence strains inject more YopP into the cytosol of eukaryotic target
      cells than do low-virulence strains.

PMID- 12065491
TI  - Immunogenicity and protective efficacy of neonatal vaccination against Bordetella
      pertussis in a murine model: evidence for early control of pertussis.
AB  - A significant resurgence of early cases of pertussis is being observed in infants
      too young to have yet completed their three-dose vaccination schedule. In this
      study, murine models of immunization and Bordetella pertussis challenge were
      adapted to early life. This allowed comparative evaluation of immunogenicity and
      protective efficacy of immunization initiated in the neonatal period (7-day-old
      mice) or in infancy (3-week-old mice) with diphtheria-tetanus-whole-cell
      pertussis (DTPw) and diphtheria-tetanus-acellular pertussis (DTPa) vaccines.
      Neonatal DTPa vaccination induced strong pertussis-specific antibody and memory
      responses. Patterns of bacterial clearance were similar in both age groups. In
      contrast, as observed in human neonates, neonatal DTPw priming did not induce
      significant antibody responses to pertussis toxin (PT) and filamentous
      hemagglutinin (FHA) and even interfered with subsequent antibody responses.
      However, this did not reflect induction of permanent neonatal tolerance, as
      antigen-specific antibodies could be elicited by subsequent exposure to DTPa.
      Furthermore, despite these blunted PT and FHA antibody responses, the protective
      efficacy of DTPw in neonatal mice proved similar to that in infant mice,
      resulting in complete bacterial clearance at day 8 after B. pertussis challenge.
      Thus, neonatal priming with antipertussis vaccines should be considered to reduce
      the window of vulnerability to pertussis at the time of its greatest severity.

PMID- 12065492
TI  - Clearance of Helicobacter pylori Infection and Resolution of Postimmunization
      Gastritis in a Kinetic Study of Prophylactically Immunized Mice.
AB  - Patients infected with Helicobacter pylori mount an immune response which fails
      to clear the infection and may contribute to disease. Mice can be protected by
      immunization. To further characterize the H. pylori-mouse model, stomachs of
      unimmunized or intranasally immunized C57BL/6 mice were quantitatively cultured 3
      days and 1, 2, 4, 8, 16, 32, and 52 weeks after challenge with H. pylori. At 3
      days and 1 week after challenge, colonization was the same in the immunized and
      unimmunized mice. By 2 weeks after challenge, the immunized mice had a >2-log
      decrease in bacterial load, and at all later time points, they either were
      culture negative or had at least a 2-log decrease in bacterial load. Gastritis in
      the immunized mice peaked at 1 to 2 weeks after challenge and was characterized
      by a mixed inflammatory infiltrate and epithelial proliferation centered at the
      transition between corpus and antrum. By 52 weeks postchallenge, the gastric
      histology in the immunized mice was not different from that in control
      unchallenged mice. The unimmunized group began to show a reduction in bacterial
      load as early as 16 weeks after challenge, and by 52 weeks seven of eight
      unimmunized mice had developed gastritis and reduced bacterial loads. These
      results indicate that prophylactic immunization does not prevent colonization by
      H. pylori but enables mice to clear the infection or significantly reduce the
      number of colonizing bacteria. The reduction in bacterial load is associated with
      gastric inflammation that subsides over time.

PMID- 12065493
TI  - Role of signal sequence in vaccine-induced protection against experimental
      coccidioidomycosis.
AB  - The vaccine efficacy of the gene sequence encoding the signal peptide of the
      antigen known as antigen 2 or proline-rich antigen (Ag2/PRA), an immunodominant
      antigen present in the cell wall of the fungal pathogen Coccidioides immitis, was
      investigated in a murine model of coccidioidomycosis. Expression plasmids for
      Ag2/PRA(1-18) DNA (signal sequence), Ag2/PRA(19-194) DNA (lacking the signal
      sequence), and Ag2/PRA(1-194) DNA (full length) were inserted in the pVR1012
      vector, and the constructs were used to vaccinate the highly susceptible BALB/c
      mouse strain. Immunization with the signal gene sequence significantly reduced
      the fungal burden in the lungs and spleens of mice 12 days after intraperitoneal
      challenge with a lethal dose of 2,500 C. immitis arthroconidia, to a level
      comparable to the protection induced in mice immunized with the full-length
      Ag2/PRA(1-194) DNA. The Ag2/PRA(19-194) gene protected mice but to a
      significantly lower level than the signal sequence or the full-length Ag2 gene.
      The immunizing capacity of Ag2/PRA(1-18) was not attributable to a nonspecific
      immunostimulatory effect of DNA, as evidenced by the fact that mice immunized
      with a frameshift mutation of Ag2/PRA(1-18) were not protected against challenge.
      Furthermore, a synthetic peptide corresponding to the translated sequence of
      Ag2/PRA(1-18) DNA protected mice, albeit at a lower level than the Ag2/PRA(1-18)
      DNA vaccine. The protection induced with the signal gene vaccine correlated with
      the production of gamma interferon when splenocytes from Ag2/PRA(1-18)-immunized
      mice were stimulated with recombinant full-length Ag2 and was not associated with
      the production of anti-Coccidioides immunoglobulin G antibody. This is the first
      study to establish that a signal peptide sequence alone, administered as a gene
      vaccine or synthetic peptide, can induce protective immunity against a microbial
      pathogen.

PMID- 12065494
TI  - MD-2, a novel accessory molecule, is involved in species-specific actions of
      Salmonella lipid A.
AB  - Salmonella lipid A is inactive in human macrophages despite being potently active
      in murine macrophages. We investigated the molecular basis for this species
      specific action of Salmonella lipid A. When murine CD14 (mCD14), mTLR4, and mMD-2
      were all expressed in human monocytic THP-1 cells, these cells were capable of
      responding to Salmonella lipid A. Expressing each of these proteins separately
      did not impart such responsiveness. Expression of mTLR4 plus mMD-2, but not mCD14
      plus mTLR4 or mCD14 plus mMD-2, conferred this responsiveness. In THP-1 cells
      expressing mCD14, mTLR4, and mMD-2, replacing mCD14 with human CD14 had no effect
      on responsiveness to Salmonella lipid A or synthetic Salmonella-type lipid A
      (compound 516). When mTLR4 was replaced with human TLR4, the responses to these
      lipid A preparations were decreased to half, and the replacement of mMD-2
      decreased responsiveness to one-third, although the responses to Escherichia coli
      lipid A or synthetic E. coli-type lipid A (compound 506) were not affected. These
      results indicate that both TLR4 and MD-2 participate in the species-specific
      action of Salmonella lipid A.

PMID- 12065495
TI  - Identification of the lipooligosaccharide biosynthesis gene lic2B as a putative
      virulence factor in strains of nontypeable Haemophilus influenzae that cause
      otitis media.
AB  - Nontypeable (NT) strains of Haemophilus influenzae are an important cause of
      acute otitis media (OM). The pathogenic process by which NT H. influenzae strains
      cause OM is poorly understood. In order to identify specific virulence factors
      important for OM pathogenesis, genomic subtraction of the NT H. influenzae middle
      ear isolate G622 against H. influenzae strain Rd was conducted and the resulting
      subtraction products were used to screen a panel of H. influenzae isolates.
      Subtraction identified 36 PCR fragments unique to strain G622, which were used in
      a preliminary screen of 48 middle ear isolates and 46 nasopharyngeal and throat
      isolates to identify genes found more frequently among middle ear isolates. These
      experiments identified a PCR fragment with high homology to the
      lipooligosaccharide biosynthesis gene lic2B (originally identified in an H.
      influenzae type b strain) among 52% of the middle ear isolates and 9% of
      nasopharyngeal and throat isolates. The lic2B gene cloned from NT H. influenzae
      strain G622 was 99% identical at the amino acid level to that of the H.
      influenzae type b strain RM7004. The lic2B gene was used to screen a larger panel
      of H. influenzae isolates including the original 48 middle ear isolates, 40
      invasive type b isolates, 90 NT H. influenzae throat isolates from children
      attending day care, and 32 NT H. influenzae nasopharyngeal clinical isolates. The
      lic2B gene was found 3.7 times more frequently among middle ear isolates than in
      throat isolates from children attending day care. These data suggest that a
      specific NT H. influenzae gene is associated with OM.

PMID- 12065497
TI  - The Babesia bovis merozoite surface antigen 2 locus contains four tandemly
      arranged and expressed genes encoding immunologically distinct proteins.
AB  - Members of the variable merozoite surface antigen (vmsa) gene family of Babesia
      bovis encode membrane proteins involved in erythrocyte invasion. In this study,
      we have identified and sequenced the complete 8.3-kb genomic locus containing msa
      2, a member of the vmsa family, in the biologically cloned Mexico Mo7 strain.
      Four tandemly arranged copies of msa-2-related genes were found in the locus. The
      four genes, designated msa-2a(1) (which corresponds to the originally described
      msa-2 gene), msa-2a(2), msa-2b, and msa-2c, were shown to be transcribed and
      expressed and encode proteins with open reading frames ranging in size from 266
      (MSA-2c) to 317 (MSA-2a(1)) amino acids. MSA-2a(1) and -2a(2) are the most
      closely related of the four proteins (90% identity), differing by (i) the number
      of 24-amino-acid repeats that comprise a surface-exposed B-cell epitope and (ii)
      the presence of a 32-amino-acid area of recombination between MSA-2a(2) and -2b.
      In contrast, msa-2c is most closely related to the previously described babr 0.8
      gene in Australia strains of B. bovis. Comparison of MSA-2 proteins in the
      Argentina R1A strain of B. bovis with the Mexico Mo7 clone revealed a relatively
      high degree of conservation (83.6, 69.4, 79.1, and 88.7% amino acid identity for
      MSA-2a(1), -2a(2), -2b, and -2c, respectively), in contrast to the extensive MSA
      1 sequence variation (52% identity) between the same two strains. Postinfection
      bovine immune serum contains antibodies that bound to each of the recombinant MSA
      2 proteins. Blocking assays demonstrated the presence of unique B-cell epitopes
      in MSA-2a(1), -2b, and -2c. The results support the evolution of the msa-2 locus
      through at least two gene duplications, with selection for multiple related but
      antigenically distinct merozoite surface proteins.

PMID- 12065496
TI  - Mechanisms of monophosphoryl lipid A augmentation of host responses to
      recombinant HagB from Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis, a gram-negative, black-pigmented anaerobe, is among the
      microorganisms implicated in the etiology of adult periodontal disease. This
      bacterium possesses a number of factors, including hemagglutinins, of potential
      importance in virulence. Our laboratory has shown the induction of protection to
      P. gingivalis infection after subcutaneous immunization with recombinant
      hemagglutinin B (rHagB). The purpose of this study was to determine if humoral
      antibody responses are induced after intranasal (i.n.) immunization of rHagB and
      if monophosphoryl lipid A (MPL), a nontoxic derivative of the lipid A region of
      lipopolysaccharide, acts as a mucosal adjuvant and potentiates responses to
      rHagB. Further, the effects of MPL on the nature of the response to HagB and on
      the costimulatory molecules B7-1 and B7-2 on different antigen-presenting cells
      (APC) were evaluated. Groups of BALB/c mice were immunized three times (2-week
      intervals) by the i.n. route with HagB (20 microg) alone or with MPL (25 microg).
      A group of nonimmunized mice served as control. Serum and saliva samples were
      collected prior to immunization and at approximately 2-week intervals and
      evaluated for serum immunoglobulin G (IgG) and IgG subclass and for salivary IgA
      antibody activity by enzyme-linked immunosorbent assay. Mice immunized with rHagB
      plus MPL had significantly higher salivary IgA (P < 0.05) and serum IgG (P <
      0.05) anti-HagB responses than mice immunized with rHagB alone. The IgG1 and
      IgG2a subclass responses seen in mice immunized with rHagB plus MPL were
      significantly higher (P < 0.05) than those seen in mice immunized with rHagB
      only. Further, the IgG2a/IgG1 ratio in the latter group was approximately 1,
      whereas in mice immunized with rHagB plus MPL the ratio was <1. These results
      provide evidence for the participation of T helper (Th) 1 and Th2 cells in
      responses to rHagB and that MPL potentiates a type 2 response to HagB. MPL was
      also shown to preferentially up-regulate B7-2 expression on B cells, whereas a
      preferential increase in B7-1 costimulatory molecule was seen on macrophages and
      dendritic cells. These results provide evidence that MPL exerts a differential
      regulation in the expression of costimulatory molecules on APC.

PMID- 12065498
TI  - Identification of a disulfide isomerase protein of Leishmania major as a putative
      virulence factor.
AB  - Several approaches have been previously used to elucidate the genetic basis of
      Leishmania virulence. In general, they were based on laboratory Leishmania clones
      genetically modified or grown in the presence of selecting agents. In a previous
      study, we demonstrated that Leishmania major freshly isolated from human
      cutaneous lesions showed significant differences in the severity of the
      experimental disease induced in BALB/c mice. Here, using the mRNA differential
      display technique, we analyzed gene expression in L. major promastigotes showing
      different levels of virulence. We have identified a novel Leishmania gene
      encoding a 477-amino-acid protein exhibiting two distinct regions that are
      identical to the putative active-site sequence (CGHC) of the eukaryotic protein
      disulfide isomerase (PDI). The recombinant protein displayed a specific PDI
      enzymatic activity. This L. major disulfide isomerase protein (LmPDI) is
      predominantly expressed, at both the mRNA and protein levels, in highly virulent
      strains. Specific PDI inhibitors abolished the enzymatic activity of the
      recombinant protein and profoundly affected parasite growth. These findings
      suggest that LmPDI may play an important role in Leishmania natural pathogenicity
      and may constitute a new target for anti-Leishmania chemotherapy.

PMID- 12065499
TI  - Synergic effects of mycoplasmal lipopeptides and extracellular ATP on activation
      of macrophages.
AB  - Mycoplasmal lipopeptides S-(2,3-bispalmitoyloxypropyl)-CGDPKHSPKSF and S-(2,3
      bispalmitoyloxypropyl)-CGNNDESNISFKEK activated a monocytic cell line, THP-1
      cells, to produce tumor necrosis factor alpha. The activity of the lipopeptides
      was augmented by ATP in a dose-dependent manner. In addition, the level of
      expression of mRNAs for tumor necrosis factor alpha and interleukin-1 beta, -6,
      and -8 was also upregulated by the lipopeptides and/or extracellular ATP, but
      that of interleukin-10 was not. The P2X purinergic receptor antagonists pyridoxal
      phosphate 6-azophenyl 2',4'-disulfonic acid and periodate-oxidized ATP suppressed
      the activity of ATP to augment the activation of THP-1 cells by the lipopeptides,
      suggesting that P2X receptors play important roles in the activity of ATP. The
      nuclear factor kappa B inhibitor dexamethasone also suppressed the activity,
      suggesting that the activity of ATP is dependent upon the nuclear factor kappa B.
      Thus, these results suggest that the interaction of extracellular ATP with the
      P2X receptors is attributed to the activity of ATP to augment the activation of
      THP-1 cells by mycoplasmal lipopeptides.

PMID- 12065500
TI  - Safety and shedding of an attenuated strain of Listeria monocytogenes with a
      deletion of actA/plcB in adult volunteers: a dose escalation study of oral
      inoculation.
AB  - Listeria monocytogenes is an intracellular bacterial pathogen which causes
      bacteremia and has a tropism for the central nervous system and a propensity to
      cause maternofetal infection. L. monocytogenes has been shown to be an effective
      prophylactic and a therapeutic vaccine vector for viral and tumor antigens in
      animal models. L. monocytogenes mutants lacking the ActA protein, which is
      essential for intracellular movement, are attenuated but retain immunogenicity in
      mice. Given the pathogenic potential of L. monocytogenes, we created an
      attenuated mutant strain bearing double deletions in the actA and plcB virulence
      genes for an initial clinical safety study of a prototype L. monocytogenes vector
      in adults. Twenty healthy volunteers received single escalating oral doses (10(6)
      to 10(9) CFU, 4 volunteers per dose cohort) of this attenuated L. monocytogenes,
      designated LH1169. Volunteers were monitored in the hospital for 14 days with
      frequent clinical checks and daily blood and stool cultures, and they were
      monitored for six additional weeks as outpatients. There were no positive blood
      cultures and no fevers attributable to the investigational inoculation. Most
      volunteers shed vaccine bacteria for 4 days or less, without diarrhea. One
      volunteer had a late positive stool culture during outpatient follow-up. Three
      volunteers had abnormal liver function test results temporally associated with
      inoculation; one could be reasonably attributed to another cause. In the highest
      dose cohort, humoral, mucosal, and cellular immune responses to the
      investigational organism were detected in individual volunteers. Attenuated L.
      monocytogenes can be studied in adult volunteers without serious long-term health
      sequelae.

PMID- 12065502
TI  - Expression of the Plasmodium falciparum immunodominant epitope (NANP)(4) on the
      surface of Salmonella enterica using the autotransporter MisL.
AB  - Gram-negative bacterial proteins which are exported from the cytosol to the
      external environment by the type V secretion system are also known as
      autotransporters. Once translocated to the periplasmic compartment by the sec
      dependent general secretory pathway, their C-terminal domain forms a pore through
      which the N-terminal domain travels to the outer membrane without the need of
      other accessory proteins. MisL (protein of membrane insertion and secretion) is a
      protein of unknown function located in the pathogenicity island SPI-3 of
      Salmonella enterica and classified as an autotransporter due to its high homology
      to Escherichia coli AIDA-I. In the present work, the MisL C-terminal translocator
      domain was used to display the immunodominant B-cell epitope of the
      circumsporozoite protein (CSP) from Plasmodium falciparum on the surface of
      Salmonella enterica serovar Typhimurium (serovar Typhimurium SL3261) and serovar
      Typhi (serovar Typhi CVD 908). The MisL beta domain was predicted by alignment
      with AIDA-I, amplified from serovar Typhimurium SL3261, cloned in a plasmid fused
      to four repeats of the tetrapeptide NANP behind the Escherichia coli heat-labile
      enterotoxin B subunit signal peptide to ensure periplasmic traffic, and expressed
      under the control of the anaerobically inducible nirB promoter. The fusion
      protein was translocated to the outer membrane of both bacterial strains,
      although the foreign epitope was displayed more efficiently in serovar
      Typhimurium SL3261, which elicited a better specific antibody response in BALB/c
      mice. More importantly, antibodies were able to recognize the native CSP in P.
      falciparum sporozoites. These results confirm that MisL is indeed an
      autotransporter and that it can be used to express foreign immunogenic epitopes
      on the surface of gram-negative bacteria.

PMID- 12065501
TI  - Inhibition of leukocyte rolling by nitric oxide during sepsis leads to reduced
      migration of active microbicidal neutrophils.
AB  - We developed two models of sepsis with different degrees of severity, sublethal
      and lethal sepsis, induced by cecal ligation and puncture. Lethal sepsis induced
      by cecal ligation and puncture (L-CLP) resulted in failure of neutrophil
      migration to the infection site and high mortality. Treatment of septic animals
      with aminoguanidine (AG), a nitric oxide (NO) synthase inhibitor, precluded the
      failure of neutrophil migration and protected the animals from death. However,
      cytokine-induced NO synthase (iNOS)-deficient (iNOS(-/-)) mice subjected to L-CLP
      did not present neutrophil migration failure, but 100% lethality occurred. iNOS(
      /-) mice subjected to sublethal sepsis induced by cecal ligation and puncture (SL
      CLP) also suffered high mortality despite the occurrence of neutrophil migration.
      This apparent paradox could be explained by the lack of microbicidal activity in
      neutrophils of iNOS(-/-) mice present at the infection site due to their
      inability to produce NO. Notably, SL- and L-CLP iNOS(-/-) mice showed high
      bacterial numbers in exudates. The inhibition of neutrophil migration by NO is
      due to inhibition of a neutrophil/endothelium adhesion mechanism, since a
      reduction in leukocyte rolling, adhesion, and emigration was observed in L-CLP
      wild-type mice. These responses were prevented by AG treatment and were not
      observed in the iNOS(-/-) L-CLP group. There was no significant change in L
      selectin expression in neutrophils from L-CLP mice. Thus, it seems that the
      decrease in leukocyte rolling is due to a defect in the expression of adhesion
      molecules on endothelial surfaces mediated by iNOS-derived NO. In conclusion, the
      results indicate that despite the importance of NO in neutrophil microbicidal
      activity, its generation in severe sepsis reduces neutrophil migration by
      inhibiting leukocyte rolling and their firm adhesion to the endothelium, in
      effect impairing the migration of leukocytes and consequently their fundamental
      role in host cell defense mechanisms.

PMID- 12065503
TI  - Neisseria lactamica protects against experimental meningococcal infection.
AB  - Immunological and epidemiological evidence suggests that the development of
      natural immunity to meningococcal disease results from colonization of the
      nasopharynx by commensal Neisseria spp., particularly with N. lactamica. We
      report here that immunization with N. lactamica killed whole cells, outer
      membrane vesicles, or outer membrane protein (OMP) pools and protected mice
      against lethal challenge by a number of diverse serogroup B and C meningococcal
      isolates in a model of bacteremic infection. Sera raised to N. lactamica killed
      whole cells, OMPs, or protein pools were found to cross-react with meningococcal
      isolates of a diverse range of genotypes and phenotypes. The results confirm the
      potential of N. lactamica to form the basis of a vaccine against meningococcal
      disease.

PMID- 12065504
TI  - Dual control of streptokinase and streptolysin S production by the covRS and
      fasCAX two-component regulators in Streptococcus dysgalactiae subsp. equisimilis.
AB  - Synthesis of the plasminogen activator streptokinase (SK) by group A streptococci
      (GAS) has recently been shown to be subject to control by two two-component
      regulators, covRS (or csrRS) and fasBCA. In independent studies, response
      regulator CovR proved to act as the repressor, whereas FasA was found to act
      indirectly as the activator by controlling the expression of a stimulatory RNA,
      fasX. In an attempt at understanding the regulation of SK production in the human
      group C streptococcal (GCS) strain H46A, the strongest SK producer known yet, we
      provide here physical and functional evidence for the presence of the cov and fas
      systems in GCS as well and, using a mutational approach, compare the balance
      between their opposing actions in H46A and GAS strain NZ131. Sequence analysis
      combined with Southern hybridization revealed that the covRS and fasCAX operons
      are preserved at high levels of primary structure identity between the
      corresponding GAS and GCS genes, with the exception of fasB, encoding a second
      sensor kinase that is not a member of the GCS fas operon. This analysis also
      showed that wild-type H46A is actually a derepressed mutant for SK and
      streptolysin S (SLS) synthesis, carrying a K102 amber mutation in covR. Using cov
      and fas mutations in various combinations together with strain constructs
      allowing complementation in trans, we found that, in H46A, cov and fas contribute
      to approximately equal negative and positive extents, respectively, to
      constitutive SK and SLS activity. The amounts of SK paralleled the level of
      skc(H46A) transcription. The most profound difference between H46A and NZ131
      regarding the relative activities of the cov and fas systems consisted in
      significantly higher activity of a functional CovR repressor in NZ131 than in
      H46A. In NZ131, CovR decreased SK activity in a Fas(+) background about
      sevenfold, compared to a 1.9-fold reduction of SK activity in H46A. Combined with
      the very short-lived nature of covR mRNA (decay rate, 1.39/min), such differences
      may contribute to strain-specific peculiarities of the expression of two
      prominent streptococcal virulence factors in response to environmental changes.

PMID- 12065506
TI  - Regulation of proinflammatory cytokines in human lung epithelial cells infected
      with Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae is a small bacterium without a cell wall that causes
      tracheobronchitis and atypical pneumonia in humans. It has also been associated
      with chronic conditions, such as arthritis, and extrapulmonary complications,
      such as encephalitis. Although the interaction of mycoplasmas with respiratory
      epithelial cells is a critical early phase of pathogenesis, little is known about
      the cascade of events initiated by infection of respiratory epithelial cells by
      mycoplasmas. Previous studies have shown that M. pneumoniae can induce
      proinflammatory cytokines in several different study systems including cultured
      murine and human monocytes. In this study, we demonstrate that M. pneumoniae
      infection also induces proinflammatory cytokine expression in A549 human lung
      carcinoma cells. Infection of A549 cells resulted in increased levels of
      interleukin-8 (IL-8) and tumor necrosis factor alpha mRNA, and both proteins were
      secreted into culture medium. IL-1 beta mRNA also increased after infection and
      IL-1 beta protein was synthesized, but it remained intracellular. In contrast,
      levels of IL-6 and gamma interferon mRNA and protein remained unchanged or
      undetectable. Using protease digestion and antibody blocking methods, we found
      that M. pneumoniae cytoadherence is important for the induction of cytokines. On
      the other hand, while M. pneumoniae protein synthesis and DNA synthesis do not
      appear to be prerequisites for the induction of cytokine gene expression, A549
      cellular de novo protein synthesis is responsible for the increased cytokine
      protein levels. These results suggest a novel role for lung epithelial cells in
      the pathogenesis of M. pneumoniae infection and provide a better understanding of
      M. pneumoniae pathology at the cellular level.

PMID- 12065505
TI  - Macrophage-induced genes of Legionella pneumophila: protection from reactive
      intermediates and solute imbalance during intracellular growth.
AB  - A promoter-probe strategy was devised to identify genes specifically expressed by
      Legionella pneumophila during growth within the macrophage. Random fragments from
      the L. pneumophila chromosome were inserted upstream of a promoterless phage T4
      td gene, and fragments that led to complementation of thymine auxotrophy during
      intracellular growth of the bacterium were identified. Two different selection
      strategies were employed to eliminate promoters that were also active during
      extracellular growth of the bacterium. Some of these genes were identified
      independently by using both of the selection strategies. The factors identified
      include orthologs of efflux-mediated resistance determinants and transporters, a
      transporter involved in protection from osmotic stress, a stress response GTP
      binding protein, a response regulator, a sensor kinase, and two systems that
      increase the reducing potential of the bacterium, one of which encodes the L.
      pneumophila ortholog of ahpC. Five of the clones analyzed here were fusions to
      promoters that were closely linked to genes encoding three-component chemiosmotic
      efflux pumps that export heavy metals or toxic organic compounds. Analysis of
      ahpC gene expression indicates that levels increased at least sevenfold during
      intracellular growth of the bacterium. Inactivation of several of the genes at
      their chromosomal loci had no effect on the intracellular growth rate of L.
      pneumophila in cultured macrophages. This suggests that a number of genes with
      increased expression during intracellular growth may be part of redundant systems
      that allow survival and growth under the conditions encountered within host
      cells.

PMID- 12065508
TI  - Essential role for cyclic AMP and its receptor protein in Yersinia enterocolitica
      virulence.
AB  - Insertion mutations were isolated in cya and crp of Yersinia enterocolitica,
      which encode adenylate cyclase and the cyclic AMP (cAMP) receptor protein (CRP).
      The cya and crp mutants were affected for the production of proteins exported by
      the Ysc, Ysa, and flagellar type III secretion systems (TTSS). Protein production
      by each TTSS was restored when the respective mutation was complemented by a
      plasmid-encoded copy of the wild-type gene. Both cya and crp mutants exhibited
      reduced virulence for orally infected BALB/c mice in a 50% lethal dose analysis.
      Examination of bacterial survival in host tissues showed that cya and crp mutants
      colonized Peyer's patches and, to a lesser extent, mesenteric lymph nodes.
      However, the mutants did not appear to disseminate to the liver and spleen of
      infected mice. An initial examination of the effectiveness of Y. enterocolitica
      cya and crp mutants to stimulate protective immunity against subsequent challenge
      with virulent bacteria in mice was promising. The results indicate that the cAMP
      CRP regulatory system is required for Y. enterocolitica virulence.

PMID- 12065507
TI  - Chronic helminth infection induces alternatively activated macrophages expressing
      high levels of CCR5 with low interleukin-12 production and Th2-biasing ability.
AB  - Helminth infections induce Th2-type biased immune responses. Although the
      mechanisms involved in this phenomenon are not yet clearly defined, antigen
      presenting cells (APC) could play an important role in this process. Here, we
      have used peritoneal macrophages (F4/80+) recruited at different times after
      challenge with Taenia crassiceps as APC and tested their ability to regulate
      Th1/Th2 differentiation. Macrophages from acute infections produced high levels
      of interleukin-12 (IL-12) and nitric oxide (NO), paralleled with low levels of IL
      6 and prostaglandin E(2) (PGE(2)) and with the ability to induce strong antigen
      specific CD4+ T-cell proliferation in response to nonrelated antigens. In
      contrast, macrophages from chronic infections produced higher levels of IL-6 and
      PGE(2) and had suppressed production of IL-12 and NO, associated with a poor
      ability to induce antigen-specific proliferation in CD4+ T cells. Failure to
      induce proliferation was not due to a deficient expression of accessory
      molecules, since major histocompatibility complex class II, CD40, and B7-2 were
      up-regulated, together with CD23 and CCR5 as infection progressed. These
      macrophages from chronic infections were able to bias CD4+ T cells to produce IL
      4 but not gamma interferon (IFN-gamma), contrary to macrophages from acute
      infections. Blockade of B7-2 and IL-6 and inhibition of PGE(2) failed to restore
      the proliferative response in CD4+ T cells. Furthermore, studies using STAT6(-/-)
      mice revealed that STAT6-mediated signaling was essential for the expansion of
      these alternatively activated macrophages. These data demonstrate that helminth
      infections can induce different macrophage populations that have Th2-biasing
      properties.

PMID- 12065509
TI  - Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts
      epithelial barrier function in a caspase-3-dependent manner.
AB  - We recently demonstrated that Giardia lamblia rearranges cytoskeletal proteins
      and reduces transepithelial electrical resistance. The effect of G. lamblia on
      enterocyte apoptosis is unknown, and a possible link between microbially induced
      enterocyte apoptosis and altered epithelial permeability has yet to be
      established. The aim of this study was to assess whether G. lamblia induces
      enterocyte apoptosis in duodenal epithelial monolayers and whether this effect
      increases epithelial permeability. Monolayers of nontransformed human duodenal
      epithelial cells were incubated with sonicated or live G. lamblia trophozoites
      (NF, S2, WB, or PB strains) for 8, 24, and 48 h. Cell cultures were assessed for
      apoptosis by Hoechst fluorescence staining, enzyme-linked immunosorbent assay for
      apoptotic nucleosomes, and electron microscopy. In separate experiments,
      monolayers were pretreated with or without 120 microM caspase-3 inhibitor (Z-DEVD
      FMK) for 1 h and were assessed for production of apoptotic nucleosomes, tight
      junctional integrity (with fluorescent ZO-1 staining followed by confocal laser
      microscopy), and transepithelial permeability for fluorescein isothiocyanate
      dextran. G. lamblia strains NF and S2, but not strains WB or PB, induced
      enterocyte apoptosis within the monolayers, and this effect was inhibited by Z
      DEVD-FMK pretreatment. Using the G. lamblia NF isolate, additional experiments
      investigated the possible link between enterocyte apoptosis and altered
      epithelial permeability. G. lamblia NF disrupted tight junctional ZO-1 and
      increased epithelial permeability, but these effects were also prevented by
      pretreatment with the caspase-3 inhibitor. These findings indicate that strain
      dependent induction of enterocyte apoptosis may contribute to the pathogenesis of
      giardiasis. This effect is responsible for a loss of epithelial barrier function
      by disrupting tight junctional ZO-1 and increasing permeability in a caspase-3
      dependent manner.

PMID- 12065510
TI  - Improved tuberculosis DNA vaccines by formulation in cationic lipids.
AB  - Mice were vaccinated with plasmid DNA (pDNA) encoding antigen 85A (Ag85A), Ag85B,
      or PstS-3 from Mycobacterium tuberculosis either in saline or formulated for
      intramuscular injections in VC1052:DPyPE (aminopropyl-dimethyl-myristoleyloxy
      propanaminium bromide-diphytanoylphosphatidyl-ethanolamine) (Vaxfectin; Vical,
      Inc., San Diego, Calif.) or for intranasal instillations in GAP-DLRIE:DOPE
      (aminopropyl-dimethyl-bis-dodecyloxy-propanaminium bromide-dioleoylphosphatidyl
      ethanolamine). These two novel cationic and neutral colipid formulations were
      previously reported to be effective adjuvants for pDNA-induced antibody
      responses. The levels of Ag85-specific total immunoglobulin G (IgG) and IgG
      isotypes were all increased 3- to 10-fold by formulation of pDNA in Vaxfectin.
      The level of production of splenic T-cell-derived Th1-type cytokines (interleukin
      2 and gamma interferon) in response to purified Ag85 and to synthetic peptides
      spanning the entire Ag85A protein was also significantly higher in animals
      vaccinated with pDNA formulated in Vaxfectin. Cytolytic T-lymphocyte responses
      generated by pDNA encoding phosphate-binding protein PstS-3 in Vaxfectin were
      better sustained over time than were those generated by PstS-3 DNA in saline.
      Intranasal immunization with Ag85A DNA in saline was completely ineffective,
      whereas administration in GAP-DLRIE:DOPE induced a positive Th1-type cytokine
      response; however, the extent of the latter response was clearly lower than that
      obtained following intramuscular immunization with the same DNA dose. Combined
      intramuscular and intranasal administrations in cationic lipids resulted in
      stronger immune responses in the spleen and, more importantly, in the lungs as
      well. Finally, formulation in Vaxfectin increased the protective efficacy of the
      Ag85B DNA vaccine, as measured by reduced relative light unit counts and CFU
      counts in the spleen and lungs from mice challenged with bioluminescent M.
      tuberculosis H37Rv. These results may be of importance for future clinical use of
      DNA vaccines in humans.

PMID- 12065511
TI  - Candida albicans hyphal formation and the expression of the Efg1-regulated
      proteinases Sap4 to Sap6 are required for the invasion of parenchymal organs.
AB  - The ability to change between yeast and hyphal cells (dimorphism) is known to be
      a virulence property of the human pathogen Candida albicans. The pathogenesis of
      disseminated candidosis involves adhesion and penetration of hyphal cells from a
      colonized mucosal site to internal organs. Parenchymal organs, such as the liver
      and pancreas, are invaded by C. albicans wild-type hyphal cells between 4 and 24
      h after intraperitoneal (i.p.) infection of mice. In contrast, a hypha-deficient
      mutant lacking the transcription factor Efg1 was not able to invade or damage
      these organs. To investigate whether this was due to the inability to undergo the
      dimorphic transition or due to the lack of hypha-associated factors, we
      investigated the role of secreted aspartic proteinases during tissue invasion and
      their association with the different morphologies of C. albicans. Wild-type cells
      expressed a distinct pattern of SAP genes during i.p. infections. Within the
      first 72 h after infection, SAP1, SAP2, SAP4, SAP5, SAP6, and SAP9 were the most
      commonly expressed proteinase genes. Sap1 to Sap3 antigens were found on yeast
      and hyphal cells, while Sap4 to Sap6 antigens were predominantly found on hyphal
      cells in close contact with host cells, in particular, eosinophilic leukocytes.
      Mutants lacking EFG1 had either noticeably reduced or higher expressed levels of
      SAP4 to SAP6 transcripts in vitro depending on the culture conditions. During
      infection, efg1 mutants had a strongly reduced ability to produce hyphae, which
      was associated with reduced levels of SAP4 to SAP6 transcripts. Mutants lacking
      SAP1 to SAP3 had invasive properties indistinguishable from those of wild-type
      cells. In contrast, a triple mutant lacking SAP4 to SAP6 showed strongly reduced
      invasiveness but still produced hyphal cells. When the tissue damage of liver and
      pancreas caused by single sap4, sap5, and sap6 and double sap4 and -6, sap5 and 
      6, and sap4 and -5 double mutants was compared to the damage caused by wild-type
      cells, all mutants which lacked functional SAP6 showed significantly reduced
      tissue damage. These data demonstrate that strains which produce hyphal cells but
      lack hypha-associated proteinases, particularly that encoded by SAP6, are less
      invasive. In addition, it can be concluded that the reduced virulence of hypha
      deficient mutants is not only due to the inability to form hyphae but also due to
      modified expression of the SAP genes normally associated with the hyphal
      morphology.

PMID- 12065512
TI  - Deletion of T cells bearing the V beta8.1 T-cell receptor following mouse mammary
      tumor virus 7 integration confers resistance to murine cerebral malaria.
AB  - Plasmodium berghei ANKA induces a fatal neurological syndrome known as cerebral
      malaria (CM) in susceptible mice. Host genetic elements are among the key factors
      determining susceptibility or resistance to CM. Analysis of mice of the same H-2
      haplotype revealed that mouse mammary tumor virus 7 (MTV-7) integration into
      chromosome 1 is one of the key factors associated with resistance to neurological
      disease during P. berghei ANKA infection. We investigated this phenomenon by
      infecting a series of recombinant inbred mice (CXD2), derived from BALB/c
      (susceptible to CM) and DBA/2 (resistant to CM) mice, with P. berghei ANKA. We
      observed differences in susceptibility to CM induced by this Plasmodium strain.
      Mice with the MTV-7 sequence in their genome were resistant to CM, whereas those
      without integration of this gene were susceptible. Thus, an integrated proviral
      open reading frame or similar genomic sequences may confer protection against
      neuropathogenesis during malaria, at least in mice.

PMID- 12065513
TI  - Effect of O acetylation of Neisseria meningitidis serogroup A capsular
      polysaccharide on development of functional immune responses.
AB  - The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis
      serogroup A polysaccharide (PS) was examined in studies using human sera and
      mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme
      linked immunosorbent assay indicated that the majority of antibodies binding to
      serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with
      mice also showed an essential role for O-acetyl groups, where serum bactericidal
      titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine
      were at least 32-fold lower than those following immunization with O-Ac PS
      conjugate vaccine and 4-fold lower than those following immunization with native
      capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the
      specificity of murine antibodies to native PS. The dramatic reduction in
      immunogenicity associated with removal of O-acetyl groups indicates that O
      acetylation is essential to the immunogenic epitopes of serogroup A PS. Since
      levels of bactericidal antibodies are correlated with protection against disease,
      O-acetyl groups appear to be important in protection.

PMID- 12065514
TI  - Mycobacterium avium genes expressed during growth in human macrophages detected
      by selective capture of transcribed sequences (SCOTS).
AB  - Selective capture of transcribed sequences (SCOTS) has been employed to identify
      54 cDNA molecules that represent 46 genes that are expressed by Mycobacterium
      avium during growth in human macrophages. Some cDNA molecules correspond to genes
      that are apparently expressed 48 h after infection of macrophages, while others
      correspond to genes expressed 110 h after infection, and still others correspond
      to genes expressed throughout the course of infection in our model system. Genes
      expressed by M. avium during growth in macrophages include genes encoding enzymes
      of several biosynthetic pathways (pyrimidines, mycobactin, and polyketides);
      genes that encode enzymes involved in intermediary metabolism, energy metabolism
      (tricarboxylic acid cycle, glyoxalate shunt), and nitrogen metabolism; and genes
      that encode regulatory proteins. A number of genes of unknown function were also
      identified, including genes that code for proteins similar to members of the PPE
      family of proteins of Mycobacterium tuberculosis and proteins similar to those
      encoded by the M. tuberculosis mce genes, which have been previously associated
      with mycobacterial virulence. The SCOTS technique, followed by enrichment for
      cDNA molecules that are up-regulated or are uniquely expressed by M. avium during
      growth in human macrophages (compared to growth in laboratory broth culture),
      allows recovery and identification of a greater diversity of cDNA molecules than
      does subtractive hybridization between cDNA mixtures from macrophage-grown and
      broth-grown M. avium. Data are presented demonstrating the reproducibility of
      recovery of a subset of cDNA molecules from cDNA mixtures purified by SCOTS on
      several different occasions. These results further demonstrate the beneficial
      utility of the SCOTS technique for identifying genes whose products are needed
      for successful survival and growth by an organism in a specific environment.

PMID- 12065515
TI  - Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in
      Leishmania amazonensis amastigotes.
AB  - Resistance to leishmanial infections depends on intracellular parasite killing by
      activated host macrophages through the L-arginine-nitric oxide (NO) metabolic
      pathway. Here we investigate the cell death process induced by NO for the
      intracellular protozoan Leishmania amazonensis. Exposure of amastigotes to
      moderate concentrations of NO-donating compounds (acidified sodium nitrite
      NaNO(2) or nitrosylated albumin) or to endogenous NO produced by
      lipopolysaccharide or gamma interferon treatment of infected macrophages resulted
      in a dramatic time-dependent cell death. The combined use of several standard DNA
      status analysis techniques (including electrophoresis ladder banding patterns,
      YOPRO-1 staining in flow cytofluorometry, and in situ recognition of DNA strand
      breaks by TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick
      end labeling] assay) revealed a rapid and extensive fragmentation of nuclear DNA
      in both axenic and intracellular NO-treated amastigotes of L. amazonensis.
      Despite some similarities to apoptosis, the nuclease activation responsible for
      characteristic DNA degradation was not under the control of caspase activity as
      indicated by the lack of involvement of cell-permeable inhibitors of caspases and
      cysteine proteases. In contrast, exposure of NO-treated amastigotes with specific
      proteasome inhibitors, such as lactacystin or calpain inhibitor I, markedly
      reduced the induction of the NO-mediated apoptosis-like process. These data
      strongly suggest that NO-induced oligonucleosomal DNA fragmentation in Leishmania
      amastigotes is, at least in part, regulated by noncaspase proteases of the
      proteasome. The determination of biochemical pathways leading up to cell death
      might ultimately allow the identification of new therapeutic targets.

PMID- 12065516
TI  - Glycoinositolphospholipids from Trypanosoma cruzi interfere with macrophages and
      dendritic cell responses.
AB  - To investigate the possible effects of glycoinositolphospholipid (GIPL) from
      Trypanosoma cruzi on human antigen presenting cells, we tested their effects on
      lipopolysaccharide (LPS)-stimulated human macrophages and dendritic cells (DC).
      Human macrophages or DC were incubated with GIPL (50 microg/ml) and LPS (500
      pg/ml) and tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), IL-10,
      and IL-12p40 levels in supernatants were analyzed by enzyme-linked immunosorbent
      assay. TNF-alpha, IL-10, and IL-12 secretion were significantly decreased by GIPL
      both in macrophages and DC. In contrast, GIPL did not alter IL-8 production. We
      also analyzed the expression of CD80, CD86, HLA-DR, CD40, and CD57 on the
      macrophage surface after stimulation with LPS in the presence or absence of T.
      cruzi GIPL. GIPL led to a down-regulation in the expression of all tested
      molecules. We additionally examined the influence of T. cruzi GIPL on the
      response of human DC to LPS. LPS-induced HLA-DR, CD83, and CD86 up-regulation was
      significantly inhibited by GIPL. A slight down-regulation in CD80 and CD40
      expression on DC surfaces in the presence of GIPL was also noticed. Similarly,
      GIPL led to down-modulation of CD83, CD80, CD86, and HLA-DR surface expression
      and TNF-alpha and IL-10 production when DC were stimulated by CD40L. The ceramide
      portion of GIPL was responsible for most of the activity exhibited by the whole
      molecule. Considering the important role of the immune response in determining
      the fate of the host-parasite relationship, the immunoregulatory activities of T.
      cruzi GIPL are potentially important for parasite evasion and then pathogenesis
      of infection with protozoan parasites.

PMID- 12065517
TI  - The Neisseria lipooligosaccharide-specific alpha-2,3-sialyltransferase is a
      surface-exposed outer membrane protein.
AB  - Neisseria gonorrhoeae and Neisseria meningitidis express an approximately 43-kDa
      alpha-2,3-sialyltransferase (Lst) that sialylates the surface lipooligosaccharide
      (LOS) by using exogenous (in all N. gonorrhoeae strains and some N. meningitidis
      serogroups) or endogenous (in other N. meningitidis serogroups) sources of 5'
      cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA). Sialylation of LOS can
      protect N. gonorrhoeae and N. meningitidis from complement-mediated serum killing
      and from phagocytic killing by neutrophils. The precise subcellular location of
      Lst has not been determined. We confirm and extend previous studies by
      demonstrating that Lst is located in the outer membrane and is surface exposed in
      both N. gonorrhoeae and N. meningitidis. Western immunoblot analysis of
      subcellular fractions of N. gonorrhoeae strain F62 and N. meningitidis strain
      MC58 not subset 3 (an acapsulate serogroup B strain) performed with rabbit
      antiserum raised against recombinant Lst revealed an approximately 43-kDa protein
      exclusively in outer membrane preparations of both pathogens. Inner membrane,
      periplasmic, cytoplasmic, and culture supernatant fractions were devoid of Lst,
      as determined by Western blot analysis. Consistent with this finding, outer
      membrane fractions of N. gonorrhoeae were significantly enriched for
      sialyltransferase enzymatic activity. A trace of enzymatic activity was detected
      in inner membrane fractions, which may have represented Lst in transit to the
      outer membrane or may have represented inner membrane contamination of outer
      membrane preparations. Subcellular preparations of an isogenic lst insertion
      knockout mutant of N. gonorrhoeae F62 (strain ST01) expressed neither a 43-kDa
      immunoreactive protein nor sialyltransferase activity. Anti-Lst rabbit antiserum
      bound to whole cells of N. meningitidis MC58 not subset 3 and wild-type N.
      gonorrhoeae F62 but not to the Lst mutant ST01, indicating the surface exposure
      of the enzyme. Although the anti-Lst antiserum avidly bound enzymatically active,
      recombinant Lst, it inhibited Lst (sialyltransferase) activity by only about 50%
      at the highest concentration of antibody used. On the contrary, anti-Lst
      antiserum did not inhibit sialylation of whole N. gonorrhoeae cells in the
      presence of exogenous CMP-NANA, suggesting that the antibody did not bind to or
      could not access the enzyme active site on the surface of viable Neisseria cells.
      Taken together, these results indicate that Lst is an outer membrane, surface
      exposed glycosyltransferase. To our knowledge, this is the first demonstration of
      the localization of a bacterial glycosyltransferase to the outer membrane of gram
      negative bacteria.

PMID- 12065518
TI  - Complement activation and formation of the membrane attack complex on serogroup B
      Neisseria meningitidis in the presence or absence of serum bactericidal activity.
AB  - Encapsulated meningococci are complement sensitive only in the presence of
      bactericidal antibodies by yet-unexplored mechanisms. The objective of this study
      was to investigate the involvement of major bacterial surface constituents on
      complement activation and membrane attack complex (MAC) formation on serogroup B
      meningococci in the presence or absence of antibody-dependent serum bactericidal
      activity (SBA). The strains used were the encapsulated H44/76, five of its
      variants differing in capsulation and expression of the class 1 porin (PorA), and
      its lipopolysaccharide (LPS)-deficient isogenic mutant (LPS(-)) pLAK33. Two
      normal sera, one with high SBA (SBA(+)) and one with no bactericidal activity
      (SBA(-)) against H44/76 as well as an a-gamma-globulinemic serum were used for
      sensibilization of the bacteria. C3b and iC3b deposition on H44/76, its
      unencapsulated variant v24, and pLAK33 was similar in SBA(+) and SBA(-) serum,
      and no difference was present between the strains. MAC deposition on H44/76 was
      higher in SBA(+) serum than in SBA(-) serum and the a-gamma-globulinemic serum.
      The amounts of C3b on H44/76, v24, and pLAK33 in the a-gamma-globulinemic serum
      were also not different, indicating immunoglobulin G (IgG)- and LPS-independent
      complement activation. H44/76 PorA(+) and its PorA(-) variant and the v24 PorA(+)
      and its PorA(-) variant incubated in SBA(-) serum induced comparable amounts of
      MAC, despite their different serum sensitivities. Complement formation on the
      surface of the bacteria occurred almost exclusively via the classical pathway,
      but the considerable amounts of Bb measured in the serum indicated alternative
      pathway activation in the fluid phase. We conclude that complement deposition on
      meningococci is, for the most part, independent of classical pathway IgG and is
      not influenced by the presence of PorA or LPS on the meningococcal surface.
      Addition of an anti-PorA chimeric antibody to the nonbactericidal normal serum,
      while promoting a dose-related bacterial lysis, did not influence the amounts of
      C3b, iC3b, and MAC formed on the bacterial surface. These findings support the
      hypothesis that proper MAC insertion rather than the quantity of MAC formed on
      the bacterial surface is of importance for efficient lysis of meningococci.

PMID- 12065519
TI  - Cellular and molecular regulation of vaccination with heat shock protein 60 from
      Histoplasma capsulatum.
AB  - Vaccination with heat shock protein 60 (Hsp60) from Histoplasma capsulatum
      induces a protective immune response in mice. We explored the cellular and
      molecular requirements for the efficacy of recombinant Hsp60 in mice. Depletion
      of CD4(+), but not CD8(+), cells during the inductive phase of vaccination
      abolished protection, as assessed by survival and by the fungal burden in lungs
      and spleens. In the expressive phase, the elimination of CD4(+) or CD8(+) cells
      after immunization did not significantly alter fungal recovery or survival from a
      lethal challenge. Depletion of both subpopulations after Hsp60 vaccination
      resulted in a failure to control a lethal infection and a higher fungal burden in
      lungs and spleens. Cytokine release by spleen cells from mice vaccinated with
      Hsp60 produced substantially more gamma interferon and interleukin-10 and -12
      than that of cells from mice immunized with either H. capsulatum recombinant
      Hsp70 or bovine serum albumin. The generation of gamma interferon, but not of
      interleukin-10, was dependent on T cells, in particular CD4(+) cells. Treatment
      of Hsp60-immunized mice with monoclonal antibody to gamma interferon or
      interleukin-10 or -12 in the inductive phase of vaccination was accompanied by
      increased recovery of yeast cells from lungs and spleens and 100% mortality.
      Likewise, the neutralization of gamma interferon or interleukin-12 abolished the
      protective effect of Hsp60 in the expressive phase. These results delineate the
      complexity of the regulatory elements necessary for vaccination against this
      fungus.

PMID- 12065520
TI  - H(2)O(2), which causes macrophage-related stress, triggers induction of
      expression of virulence-associated plasmid determinants in Rhodococcus equi.
AB  - The response of the intracellular pathogen Rhodococcus equi to H(2)O(2)
      treatment, a situation potentially encountered after the oxidative burst of
      alveolar macrophages, was analyzed. Compared to other bacteria, including
      Deinococcus radiodurans, R. equi showed exceptionally high resistance to this
      stress. A proteomic approach showed that four polypeptides present in the wild
      type strain (85F) are missing in the plasmid-cured strain 85F(P-), and by using a
      DNA macroarray, we identified two plasmid-encoded vap genes, vapA and vapG, whose
      expression was highly induced by H(2)O(2) treatment. Whereas the transcript size
      of vapA was compatible with a monocistronic mRNA, the transcript of vapG was
      considerably longer. Rapid amplification of cDNA ends PCRs showed that the
      transcriptional start sites of the two operons were 69 and 269 nucleotides (nt)
      upstream of the start codon, respectively. Analysis of these leader sequences
      revealed the presence of a small open reading frame named podG, which encodes a
      sequence of 55 amino acids preceded by a putative ribosome binding site sequence
      in the vapG transcript. Taking this result into account, the untranslated leader
      of the podG/vapG operon is 87 nt. Alignment of this sequence with the leader
      sequences of vapA and vapD, genes previously shown to be induced by acid,
      revealed significant homologies. Since our results showed that vapA, vapD, and
      vapG are genes highly induced by macrophage-related stresses, their gene products
      may, within the Vap protein family, play a dominant role inside these phagocytic
      cells and may be the most promising candidates for vaccination strategies.

PMID- 12065521
TI  - Comparative phenotypic analysis of the Bordetella parapertussis isolate chosen
      for genomic sequencing.
AB  - The genomes of three closely related bordetellae are currently being sequenced,
      thus providing an opportunity for comparative genomic approaches driven by an
      understanding of the comparative biology of these three bacteria. Although the
      other strains being sequenced are well studied, the strain of Bordetella
      parapertussis chosen for sequencing is a recent human clinical isolate (strain
      12822) that has yet to be characterized in detail. This investigation reports the
      first phenotypic characterization of this strain, which will likely become the
      prototype for this species in comparison with the prototype strains of B.
      pertussis (Tohama I), B. bronchiseptica (RB50), and other isolates of B.
      parapertussis. Multiple in vitro and in vivo assays distinguished each species.
      B. parapertussis was more similar to B. bronchiseptica than to B. pertussis in
      many assays, including in BvgS signaling characteristics, presence of urease
      activity, regulation of urease expression by BvgAS, virulence in the respiratory
      tracts of immunocompromised mice, induction of anti-Bordetella antibodies, and
      serum antimicrobial resistance. In other assays, B. parapertussis was distinct
      from all other species (in pigment production) or more similar to B. pertussis
      (by lack of motility and cytotoxicity to a macrophage-like cell line). These
      results begin to provide phenotypes that can be related to genetic differences
      identified in the genomic sequences of bordetellae.

PMID- 12065522
TI  - In vivo effects of a synthetic 2-kilodalton macrophage-activating lipopeptide of
      Mycoplasma fermentans after pulmonary application.
AB  - Mycoplasmas can cause interstitial pneumonias inducing critical illness in humans
      and animals. Mycoplasma infections are characterized by an influx of neutrophils,
      followed by an accumulation of macrophages and lymphocytes. The present study
      deals with the question of which mycoplasmal components cause this host reaction.
      The mycoplasma-derived, macrophage-activating lipopeptide 2S-MALP-2 was used to
      mimic the sequelae of a mycoplasma infection. To this end, 2S-MALP-2 was
      intratracheally instilled into the lungs of Lewis rats, and the bronchoalveolar
      lavage cells were examined at different times after different doses of 2S-MALP-2.
      Application of 2.5 microg induced a pronounced leukocyte accumulation in the
      bronchoalveolar space. At 24 h after 2S-MALP-2 administration, the majority of
      leukocytes consisted of neutrophils, followed by macrophages, peaking on days 2
      and 3. Lymphocyte numbers, although amounting to only a few percent of the total
      bronchoalveolar lavage cells, also increased significantly, with maximal
      lymphocyte accumulation occurring by 72 h after instillation. The leukocyte count
      of the lung interstitium was increased on day 3 after treatment. After 10 days
      all investigated cell populations returned to control levels. Transient
      chemotactic activity for neutrophils was detected in the bronchoalveolar lavage
      fluid early after 2S-MALP-2 application, followed by monocyte chemoattractant
      protein-1 activity (MCP-1) in lung homogenates. MCP-1 was produced by
      bronchoalveolar lavage cells upon stimulation with 2S-MALP-2. Our data indicate
      that mycoplasmal lipoproteins and lipopeptides are probably the most relevant
      mycoplasmal components for the early host reaction. The primary target cells are
      likely to be the alveolar macrophages liberating chemokines, which attract
      further leukocytes.

PMID- 12065523
TI  - Chlamydia trachomatis induces remodeling of the actin cytoskeleton during
      attachment and entry into HeLa cells.
AB  - To elucidate the host cell machinery utilized by Chlamydia trachomatis to invade
      epithelial cells, we examined the role of the actin cytoskeleton in the
      internalization of chlamydial elementary bodies (EBs). Treatment of HeLa cells
      with cytochalasin D markedly inhibited the internalization of C. trachomatis
      serovar L2 and D EBs. Association of EBs with HeLa cells induced localized actin
      polymerization at the site of attachment, as visualized by either phalloidin
      staining of fixed cells or the active recruitment of GFP-actin in viable infected
      cells. The recruitment of actin to the specific site of attachment was
      accompanied by dramatic changes in the morphology of cell surface microvilli.
      Ultrastructural studies revealed a transient microvillar hypertrophy that was
      dependent upon C. trachomatis attachment, mediated by structural components on
      the EBs, and cytochalasin D sensitive. In addition, a mutant CHO cell line that
      does not support entry of C. trachomatis serovar L2 did not display such
      microvillar hypertrophy following exposure to L2 EBs, which is in contrast to
      infection with serovar D, to which it is susceptible. We propose that C.
      trachomatis entry is facilitated by an active actin remodeling process that is
      induced by the attachment of this pathogen, resulting in distinct microvillar
      reorganization throughout the cell surface and the formation of a pedestal-like
      structure at the immediate site of attachment and entry.

PMID- 12065524
TI  - Candida albicans expresses a focal adhesion kinase-like protein that undergoes
      increased tyrosine phosphorylation upon yeast cell adhesion to vitronectin and
      the EA.hy 926 human endothelial cell line.
AB  - The signaling pathways triggered by adherence of Candida albicans to the host
      cells or extracellular matrix are poorly understood. We provide here evidence in
      C. albicans yeasts of a p105 focal adhesion kinase (Fak)-like protein (that we
      termed CaFak), antigenically related to the vertebrate p125Fak, and its
      involvement in integrin-like-mediated fungus adhesion to vitronectin (VN) and
      EA.hy 926 human endothelial cell line. Biochemical analysis with different anti
      chicken Fak antibodies identified CaFak as a 105-kDa protein and
      immunofluorescence and cytofluorimetric analysis on permeabilized cells
      specifically stain C. albicans yeasts; moreover, confocal microscopy evidences
      CaFak as a cytosolic protein that colocalizes on the membrane with the integrin
      like VN receptors upon yeast adhesion to VN. The protein tyrosine kinase (PTK)
      inhibitors genistein and herbimycin A strongly inhibited C. albicans yeast
      adhesion to VN and EA.hy 926 endothelial cells. Moreover, engagement of alpha v
      beta 3 and alpha v beta 5 integrin-like on C. albicans either by specific
      monoclonal antibodies or upon adhesion to VN or EA.hy 926 endothelial cells
      stimulates CaFak tyrosine phosphorylation that is blocked by PTK inhibitor. A
      role for CaFak in C. albicans yeast adhesion was also supported by the failure of
      VN to stimulate its tyrosine phosphorylation in a C. albicans mutant showing
      normal levels of CaFak and VNR-like integrins but displaying reduced adhesiveness
      to VN and EA.hy 926 endothelial cells. Our results suggest that C. albicans Fak
      like protein is involved in the control of yeast cell adhesion to VN and
      endothelial cells.

PMID- 12065525
TI  - Inhibition of fusion of Chlamydia trachomatis inclusions at 32 degrees C
      correlates with restricted export of IncA.
AB  - Chlamydia trachomatis is an obligate intracellular bacterium that develops within
      a parasitophorous vacuole termed an inclusion. The inclusion is nonfusogenic with
      lysosomes but intercepts lipids from a host cell exocytic pathway. Initiation of
      chlamydial development is concurrent with modification of the inclusion membrane
      by a set of C. trachomatis-encoded proteins collectively designated Incs. One of
      these Incs, IncA, is functionally associated with the homotypic fusion of
      inclusions. Inclusions also do not fuse when cultures are multiply infected with
      C. trachomatis and cultivated at 32 degrees C. We obtained evidence linking these
      experimental observations by characterizing IncA localization in 32 degrees C
      cultures. Analysis of inclusions by light and transmission electron microscopy
      confirmed that HeLa cells infected with multiple C. trachomatis elementary bodies
      and cultivated at 32 degrees C for 24 h contained multiple, independent
      inclusions. Reverse transcriptase PCR and immunoblot analyses of C. trachomatis
      infected HeLa cells demonstrated the presence of IncA at 24 h in 32 degrees C
      cultures. When parallel cultures were probed with IncA-specific antibodies in
      indirect immunofluorescence assays, IncA was detectable in intracellular
      chlamydiae but not within the inclusion membrane. In addition, analysis of
      purified reticulate bodies from 37 and 32 degrees C cultures showed that
      bacterium-associated pools of IncA are enriched in cultures grown at 32 degrees
      C. Microscopic observation of infected cells revealed that some vacuoles had
      fused by 48 h postinfection, and this finding was correlated with the detection
      of IncA in inclusion membranes by immunofluorescence microscopy. The data are
      consistent with a requirement for IncA in fusions of C. trachomatis inclusions
      and suggest that the effect of incubation at 32 degrees C is manifested by
      restricted export of IncA to the inclusion membrane.

PMID- 12065526
TI  - Fluorescence resonance energy transfer microscopy of the Helicobacter pylori
      vacuolating cytotoxin within mammalian cells.
AB  - The Helicobacter pylori vacuolating cytotoxin (VacA) binds and enters mammalian
      cells to induce cellular vacuolation. To investigate the quaternary structure of
      VacA within the intracellular environment where toxin cytotoxicity is elaborated,
      we employed fluorescence resonance energy transfer (FRET) microscopy. HeLa cells
      coexpressing full-length and truncated forms of VacA fused to cyan fluorescent
      protein (CFP) or yellow fluorescent protein (YFP) were analyzed for FRET to
      indicate direct associations. These studies revealed that VacA-CFP and VacA-YFP
      interact within vacuolated cells, supporting the belief that monomer associations
      at an intracellular site are important for the toxin's vacuolating activity. In
      addition, the two fragments of proteolytically nicked VacA, p37 and p58, interact
      when coexpressed within mammalian cells. Because p37 and p58 function in trans
      when expressed separately within mammalian cells, these data suggest that the
      mechanism by which these two fragments induce vacuolation requires direct
      association. FRET microscopy also demonstrated interactions between mutant forms
      of VacA, as well as wild-type VacA with mutant forms of the toxin within
      vacuolated cells. Finally, a dominant-negative form of the toxin directly
      associates with wild-type VacA in cells where vacuolation was not detectable,
      suggesting that the formation of complexes comprising wild-type and dominant
      negative forms of toxin acts to block intracellular toxin function.

PMID- 12065527
TI  - Human monocytes kill Shigella flexneri but then die by apoptosis associated with
      suppression of proinflammatory cytokine production.
AB  - Shigella flexneri infection of human macrophages is followed by rapid bacterial
      escape into the cytosol and secretion of IpaB, which activates caspase-1 to
      mediate cell death and release of mature interleukin (IL)-1 beta. Here we report
      a different outcome following infection of human peripheral blood monocytes. S.
      flexneri infects monocytes inefficiently in the absence of complement and,
      following complement-dependent uptake, cannot escape the endosomal compartment.
      Consequently, bacteria are killed within the first 60 min in the absence of
      monocyte cell death, as demonstrated by immunofluorescence and electron
      microscopy and enumeration of colonies in a gentamicin protection assay. Despite
      early bacterial death, wild-type S. flexneri influenced the subsequent monocyte
      proinflammatory cytokine response and cell fate. Infection with wild-type S.
      flexneri resulted in IpaB-dependent suppression of IL-1 beta, tumor necrosis
      factor alpha, and IL-6 compared with that of plasmid-cured avirulent S. flexneri
      infected cells. Furthermore, over the following 6 to 8 h, virulent S. flexneri
      infected monocytes died by apoptosis whereas avirulent infected monocytes died by
      necrosis. Together, these results imply that monocytes migrating into the
      inflammatory site during the early stages of shigellosis kill S. flexneri but
      that during bacterial uptake, they receive virulence signals from S. flexneri
      which induce delayed apoptosis associated with suppression of the proinflammatory
      cytokine response to bacterial phagocytosis. This delayed apoptosis may have
      important effects on the ordered initiation of the innate immune response,
      leading to the excessive inflammatory response characteristic of shigellosis.

PMID- 12065528
TI  - The Salmonella enterica serotype typhimurium effector proteins SipA, SopA, SopB,
      SopD, and SopE2 act in concert to induce diarrhea in calves.
AB  - Salmonella enterica serotype Typhimurium requires a functional type III secretion
      system encoded by Salmonella pathogenicity island 1 (SPI1) to cause diarrhea. We
      investigated the role of genes encoding secreted target proteins of the SPI1
      associated type III secretion system for enteropathogenicity in calves.
      Salmonella serotype Typhimurium strains having mutations in sptP, avrA, sspH1, or
      slrP induced fluid secretion in the bovine ligated ileal loop model at levels
      similar to that of the wild type. In contrast, mutations in sipA, sopA, sopB,
      sopD, or sopE2 significantly reduced fluid accumulation in bovine ligated ileal
      loops at 8 h postinfection. A strain carrying mutations in sipA, sopA, sopB,
      sopD, and sopE2 (sipA sopABDE2 mutant) caused the same level of fluid
      accumulation in bovine ligated ileal loops as a strain carrying a mutation in
      sipB, a SPI1 gene required for the translocation of effector proteins into host
      cells. A positive correlation was observed between the severity of
      histopathological lesions detected in the ileal mucosa and the levels of fluid
      accumulation induced by the different mutants. After oral infection of calves,
      the Salmonella serotype Typhimurium sipAsopABDE2 mutant caused only mild diarrhea
      and was more strongly attenuated than strains having only single mutations. These
      data demonstrate that SipA, SopA, SopB, SopD, and SopE2 are major virulence
      factors responsible for diarrhea during Salmonella serotype Typhimurium infection
      of calves.

PMID- 12065529
TI  - Progressive bovine paratuberculosis is associated with local loss of CD4(+) T
      cells, increased frequency of gamma delta T cells, and related changes in T-cell
      function.
AB  - Bovine paratuberculosis is caused by the infection of young calves with
      Mycobacterium avium subsp. paratuberculosis, resulting in a chronic granulomatous
      infection of predominantly the ileum. After an incubation period of 2 to 5 years,
      the disease becomes progressive in some of the chronically infected, but
      asymptomatic cows. This results in a protein-losing enteropathy that will
      ultimately be fatal. A loss of cell-mediated immune responses in symptomatic
      animals has been described, but no information is available concerning immune
      reactivity in the intestine. We sought to investigate putative disease status
      associated lymphocyte subset distributions and antigen-specific functional
      characteristics of mononuclear cells isolated from blood, gut-associated lymphoid
      tissue, and the intestinal walls of 22 cows in different stages of disease and in
      control animals. The results demonstrated a significant decrease in CD4(+) T-cell
      frequency and a significant increase in TcR1-N12(+) gamma delta T-cell frequency
      in ileum lamina propria lymphocytes of symptomatic animals compared to the
      asymptomatic shedders. Immunohistology revealed that there was also an absolute
      decrease in the number of CD4(+) T cells in sections of the lesional ileum. Our
      findings also indicated that both peripheral and intestinal cell-mediated
      responses are decreased in symptomatic animals compared to asymptomatic animals.
      We conclude that the decrease in cell-mediated responses is likely related to a
      loss of antigen-specific CD4(+) T cells, which is most prominent in the lesional
      ileum from symptomatic animals, thus contributing to the progressive nature of
      bovine paratuberculosis.

PMID- 12065530
TI  - Increased virulence of a fibronectin-binding protein mutant of Staphylococcus
      aureus in a rat model of pneumonia.
AB  - Fibronectin-binding proteins mediate Staphylococcus aureus internalization into
      nonphagocytic cells in vitro. We have investigated whether fibronectin-binding
      proteins are virulence factors in the pathogenesis of pneumonia by using S.
      aureus strain 8325-4 and isogenic mutants in which fibronectin-binding proteins
      were either deleted (DU5883) or overexpressed [DU5883(pFnBPA4)]. We first
      demonstrated that fibronectin-binding proteins mediate S. aureus internalization
      into alveolar epithelial cells in vitro and that S. aureus internalization into
      alveolar epithelial cells requires actin rearrangement and protein kinase
      activity. Second, we established a rat model of S. aureus-induced pneumonia and
      measured lung injury and bacterial survival at 24 and 96 h postinoculation. S.
      aureus growth and the extent of lung injury were both increased in rats
      inoculated with the deletion mutant (DU5883) in comparison with rats inoculated
      with the wild-type (8325-4) and the fibronectin-binding protein-overexpressing
      strain DU5883(pFnBPA4) at 24 h postinfection. Morphological evaluation of
      infected lungs at the light and electron microscopic levels demonstrated that S.
      aureus was present within neutrophils from both 8325-4- and DU5883-inoculated
      lungs. Our data suggest that fibronectin-binding protein-mediated internalization
      into alveolar epithelial cells is not a virulence mechanism in a rat model of
      pneumonia. Instead, our data suggest that fibronectin-binding proteins decrease
      the virulence of S. aureus in pneumonia.

PMID- 12065531
TI  - Hierarchy of susceptibility of dendritic cell subsets to infection by Leishmania
      major: inverse relationship to interleukin-12 production.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells which initiate
      and regulate T-cell immune responses. Here we show that murine splenic DCs can be
      ranked on the basis of their ability to phagocytose and harbor the obligately
      intracellular parasite Leishmania major. CD4(+) CD8(-) DCs are the most
      permissive host cells for L. major amastigotes, followed by CD4(-) CD8(-) DCs;
      CD4(-) CD8(+) cells are the least permissive. However, the least susceptible CD4(
      ) CD8(+) DC subset was the best interleukin-12 producer in response to infection.
      Infection did not induce in any DC subset production of the proinflammatory
      cytokine gamma interferon and nitric oxide associated with the induction of Th1
      responses. The number of parasites phagocytosed by DCs was low, no more than 3
      organisms per cell, compared to more than 10 organisms per macrophage. In
      infected DCs, the parasites are located in a parasitophorous vacuole containing
      both major histocompatibility complex (MHC) class II and lysosome-associated
      membrane protein 1 molecules, similar to their location in the infected
      macrophage. The parasite-driven redistribution of MHC class II to this
      compartment indicates that infected DCs should be able to present parasite
      antigen.

PMID- 12065533
TI  - Modification of type IV pilus-associated epithelial cell adherence and
      multicellular behavior by the PilU protein of Neisseria gonorrhoeae.
AB  - Expression of type IV pili (Tfp) correlates with the ability of Neisseria
      gonorrhoeae to colonize the human host, as well as with adherence to human
      epithelial tissue, twitching motility, competence for natural transformation, and
      autoagglutination. N. gonorrhoeae PilF (required for Tfp biogenesis) and PilT
      (required for twitching motility and transformation) share significant identities
      with members of a family of putative ATPases involved in membrane trafficking of
      macromolecules. An open reading frame downstream of the pilT locus encoding a 408
      amino-acid protein with 33% identity with the gonococcal PilT protein and 45%
      identity with the PilU protein in Pseudomonas aeruginosa was characterized, and
      the corresponding gene was designated pilU. Unlike N. gonorrhoeae pilT mutants,
      pilU mutants express twitching motility and are competent for DNA transformation.
      However, loss-of-function mutations in pilU increased bacterial adherence to ME
      180 human epithelial cells eightfold and disrupted in vitro Tfp-associated
      autoagglutination. Comparative alignment of N. gonorrhoeae PilU with other
      members of the TrbB-like family of traffic ATPases revealed a conserved carboxy
      terminal domain unique to family members which are not essential for Tfp
      biogenesis but which specifically modify Tfp-associated phenotypes. Studies of
      the pilT-pilU locus by using Northern blotting, transcriptional fusions, and
      reverse transcription-PCR showed that the two genes encoding closely related
      proteins with dissimilar effects on Tfp phenotypes are transcribed from a single
      promoter.

PMID- 12065532
TI  - Analysis of sequence diversity at the highly polymorphic Cpgp40/15 locus among
      Cryptosporidium isolates from human immunodeficiency virus-infected children in
      South Africa.
AB  - Cryptosporidium sp. is a significant cause of diarrheal disease, particularly in
      human immunodeficiency virus (HIV)-infected patients in developing countries. We
      recently cloned and sequenced several alleles of the highly polymorphic single
      copy Cryptosporidium parvum gene Cpgp40/15. This gene encodes a precursor protein
      that is proteolytically cleaved to yield mature cell surface glycoproteins gp40
      and gp15, which are implicated in zoite attachment to and invasion of
      enterocytes. The most-striking feature of the Cpgp40/15 alleles and proteins is
      their unprecedented degree of sequence polymorphism, which is far greater than
      that observed for any other gene or protein studied in C. parvum to date. In this
      study we analyzed nucleic acid and amino acid sequence polymorphism at the
      Cpgp40/15 locus of 20 C. parvum isolates from HIV-infected South African
      children. Fifteen isolates exhibited one of four previously identified genotype I
      alleles at the Cpgp40/15 locus (Ia, Ib, Ic, and Id), while five displayed a novel
      set of polymorphisms that defined a new Cpgp40/15 genotype I allele, designated
      genotype Ie. Surprisingly, only 15 of these isolates exhibited concordant type I
      alleles at the thrombospondin-related adhesive protein of Cryptosporidium and
      Cryptosporidium oocyst wall protein loci, while five isolates (all of which
      displayed Cpgp40/15 genotype Ic alleles) displayed genotype II alleles at these
      loci. Furthermore, the last five isolates also manifested chimeric genotype Ic/Ib
      or Ic/II alleles at the Cpgp40/15 locus, raising the possibility of sexual
      recombination within and between prototypical parasite genotypes. Lastly,
      children infected with isolates having genotype Ic alleles were significantly
      older than those infected with isolates displaying other genotype I alleles.

PMID- 12065534
TI  - Streptococcus-zebrafish model of bacterial pathogenesis.
AB  - Due to its small size, rapid generation time, powerful genetic systems, and
      genomic resources, the zebrafish has emerged as an important model of vertebrate
      development and human disease. Its well-developed adaptive and innate cellular
      immune systems make the zebrafish an ideal model for the study of infectious
      diseases. With a natural and important pathogen of fish, Streptococcus iniae, we
      have established a streptococcus- zebrafish model of bacterial pathogenesis.
      Following injection into the dorsal muscle, zebrafish developed a lethal
      infection, with a 50% lethal dose of 10(3) CFU, and died within 2 to 3 days. The
      pathogenesis of infection resembled that of S. iniae in farmed fish populations
      and that of several important human streptococcal diseases and was characterized
      by an initial focal necrotic lesion that rapidly progressed to invasion of the
      pathogen into all major organ systems, including the brain. Zebrafish were also
      susceptible to infection by the human pathogen Streptococcus pyogenes. However,
      disease was characterized by a marked absence of inflammation, large numbers of
      extracellular streptococci in the dorsal muscle, and extensive myonecrosis that
      occurred far in advance of any systemic invasion. The genetic systems available
      for streptococci, including a novel method of mutagenesis which targets genes
      whose products are exported, were used to identify several mutants attenuated for
      virulence in zebrafish. This combination of a genetically amenable pathogen with
      a well-defined vertebrate host makes the streptococcus-zebrafish model of
      bacterial pathogenesis a powerful model for analysis of infectious disease.

PMID- 12065535
TI  - Contribution of interleukin-11 and prostaglandin(s) in lipopolysaccharide-induced
      bone resorption in vivo.
AB  - We previously demonstrated that interleukin-1 (IL-1) and tumor necrosis factor
      (TNF) activities only partially account for calvarial bone resorption induced by
      local application of lipopolysaccharide (LPS) in mice. The present study was
      undertaken to determine the role and relative contribution of IL-11 and
      prostaglandin(s) (PG[s]) in LPS-induced bone resorption in vivo. A one-time dose
      of LPS was injected into the subcutaneous tissue overlying calvaria of mice
      lacking IL-1 receptor type I (IL-1RI(-/-)), mice lacking TNF receptor p55 and IL
      1RI (TNFRp55(-/-)-IL-1RI(-/-)), and wild-type mice. Mice were then treated with
      injections of anti-IL-11 monoclonal antibody (MAb), indomethacin, or phosphate
      buffered saline (PBS) and sacrificed 5 days later. Histological sections stained
      for tartrate-resistant acid phosphatase (TRAP) were quantified by
      histomorphometric analysis. At low doses of LPS (100 microg/mouse), the
      percentages of bone surface covered by osteoclasts were found to be similar in
      three strains of mice. The increase was reduced by 37% with anti-IL-11 MAb and by
      46% with indomethacin. At higher doses of LPS (500 microg/mouse), we found an
      eightfold increase in these percentages in wild-type mice and a fivefold increase
      in these percentages in IL-1RI(-/-) and TNFRp55(-/-)-IL-1RI(-/-) mice after
      normalizing with the value from the saline-PBS control group in the same strain
      of mice. The increase was reduced by 55 and 69% in wild-type mice and by 50 and
      57% in IL-1RI(-/-) and TNFRp55(-/-)-IL-1RI(-/-) mice treated with anti-IL-11 MAb
      or indomethacin, respectively. Our findings suggest that in vivo, at low doses of
      LPS (100 microg/mouse), LPS-induced bone resorption is mediated by IL-11 and PGs,
      while at high doses of LPS (500 microg/mouse), it is mediated by IL-11, PGs, IL
      1, and TNF signaling. IL-11 and PGs mediate LPS-induced bone resorption by
      enhancing osteoclastogenesis independently of the IL-1 or TNF signaling.

PMID- 12065536
TI  - Essential role of ferritin Pfr in Helicobacter pylori iron metabolism and gastric
      colonization.
AB  - The reactivity of the essential element iron necessitates a concerted expression
      of ferritins, which mediate iron storage in a nonreactive state. Here we have
      further established the role of the Helicobacter pylori ferritin Pfr in iron
      metabolism and gastric colonization. Iron stored in Pfr enabled H. pylori to
      multiply under severe iron starvation and protected the bacteria from acid
      amplified iron toxicity, as inactivation of the pfr gene restricted growth of H.
      pylori under these conditions. The lowered total iron content in the pfr mutant,
      which is probably caused by decreased iron uptake rates, was also reflected by an
      increased resistance to superoxide stress. Iron induction of Pfr synthesis was
      clearly diminished in an H. pylori feoB mutant, which lacked high-affinity
      ferrous iron transport, confirming that Pfr expression is mediated by changes in
      the cytoplasmic iron pool and not by extracellular iron. This is well in
      agreement with the recent discovery that iron induces Pfr synthesis by abolishing
      Fur-mediated repression of pfr transcription, which was further confirmed here by
      the observation that iron inhibited the in vitro binding of recombinant H. pylori
      Fur to the pfr promoter region. The functions of H. pylori Pfr in iron metabolism
      are essential for survival in the gastric mucosa, as the pfr mutant was unable to
      colonize in a Mongolian gerbil-based animal model. In summary, the pfr phenotypes
      observed give new insights into prokaryotic ferritin functions and indicate that
      iron storage and homeostasis are of extraordinary importance for H. pylori to
      survive in its hostile natural environment.

PMID- 12065537
TI  - Magnesium uptake by CorA is essential for viability of the gastric pathogen
      Helicobacter pylori.
AB  - We show here that Mg(2+) acquisition by CorA is essential for Helicobacter pylori
      in vitro, as corA mutants did not grow in media without Mg(2+) supplementation.
      Complementation analysis performed with an Escherichia coli corA mutant revealed
      that H. pylori CorA transports nickel and cobalt in addition to Mg(2+). However,
      Mg(2+) is the dominant CorA substrate, as the corA mutation affected neither
      cobalt and nickel resistance nor nickel induction of urease in H. pylori. The
      drastic Mg(2+) requirement (20 mM) of H. pylori corA mutants indicates that CorA
      plays a key role in the adaptation to the low-Mg(2+) conditions predominant in
      the gastric environment.

PMID- 12065538
TI  - Recruitment of mammalian cell fibronectin to the surface of Chlamydia
      trachomatis.
AB  - Pathogenic bacteria exploit the presence of various host cell molecules in order
      to colonize new tissues. Fibronectin is involved in a wide range of cell
      functions in vivo, and staphylococci, streptococci, and gonococci have evolved
      mechanisms to utilize this glycoprotein to mediate host cell binding. We show
      that elementary bodies (EB) from two biovars of Chlamydia trachomatis recruit
      fibronectin to their surfaces upon lysis of the host cell. We also demonstrate
      that a heparan sulfate lyase-sensitive molecule on chlamydial EB is responsible
      for binding at least a portion of this fibronectin.

PMID- 12065539
TI  - Purified malaria pigment (hemozoin) enhances dendritic cell maturation and
      modulates the isotype of antibodies induced by a DNA vaccine.
AB  - Hemozoin (malaria pigment) has been implicated in the modulation of immune
      responses during malaria infection. This study was designed to evaluate the
      effect of purified hemozoin on the in vitro activation of myeloid dendritic
      cells. Our study also revealed that in addition to enhancing the maturation of
      dendritic cells, hemozoin also greatly promotes immunoglobulin G2a antibody
      responses when coadministered with a DNA vaccine plasmid encoding Pfs25, a
      Plasmodium falciparum transmission-blocking antigen.

PMID- 12065540
TI  - Cysteine protease activity and histamine release from the human mast cell line
      HMC-1 stimulated by recombinant streptococcal pyrogenic exotoxin B/streptococcal
      cysteine protease.
AB  - We constructed the expression vector pSK-SCP containing the streptococcal
      exotoxin B gene (spe b) which expressed protease activity. We showed that the
      recombinant streptococcal pyogenic exotoxin B/streptococcal cysteine protease
      (rSPE B/SCP) was secreted into the culture supernatant of the transformant and
      retained its SCP activity, which was equivalent to or greater than that of the
      naturally occurring molecule. The secreted rSPE B/SCP induced histamine release
      and degranulation of the human mast cell line HMC-1. This study may contribute to
      the understanding of the pathogenic role of SPE B/SCP in streptococcal infection
      and streptococcal toxic shock syndrome.

PMID- 12065541
TI  - Sigma B contributes to PrfA-mediated virulence in Listeria monocytogenes.
AB  - Transcription of the Listeria monocytogenes positive regulatory factor A protein
      (PrfA) is initiated from either of two promoters immediately upstream of prfA
      (prfAp(1) and prfAp(2)) or from the upstream plcA promoter. We demonstrate that
      prfAp(2) is a functional sigma(B)-dependent promoter and that a sigB deletion
      mutation affects the virulence phenotype of L. monocytogenes. Thus, the
      alternative sigma factor sigma(B) contributes to virulence in L. monocytogenes.

PMID- 12065542
TI  - Analogous cytokine responses to Burkholderia pseudomallei strains contrasting in
      virulence correlate with partial cross-protection in immunized mice.
AB  - Cytokine mRNA levels were assessed in Burkholderia pseudomallei-susceptible
      BALB/c mice and B. pseudomallei-resistant C57BL/6 mice following administration
      of a sublethal dose of less virulent (LV) B. pseudomallei, a candidate immunogen
      tested for protection against a highly virulent (HV) challenge. Compared on the
      basis of the bacterial loads, the cytokine patterns induced by HV and LV B.
      pseudomallei were similar, involving gamma interferon, interleukin-10, and other
      cytokines. Partial cross-protection between B. pseudomallei strains is shown to
      be associated with cytokine profiles involving both type 1 and type 2 cytokines.

PMID- 12065543
TI  - Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma
      asociated cells: implications for persistent Chlamydophila pneumoniae infection.
AB  - This study shows that vascular smooth muscle cells express significantly higher
      levels of gamma interferon-inducible indoleamine 2,3-dioxygenase (IDO) activity
      than endothelium or mononuclear cells. Since IDO activity is linked to persistent
      Chlamydophila pneumoniae infection, our results suggest that smooth muscle cells
      may be an important reservoir of that organism in atherosclerosis.

PMID- 12065544
TI  - Fibrinogen binding to intercellular adhesion molecule 1: implications for
      Plasmodium falciparum adhesion.
AB  - Intercellular adhesion molecule 1 (ICAM-1) is an endothelial cell adhesion
      molecule implicated in cerebral malaria. We investigated whether fibrinogen
      affects Plasmodium falciparum binding to ICAM-1, as the ICAM-1 binding sites of
      P. falciparum and fibrinogen overlap. We show that fibrinogen dramatically
      reduces P. falciparum adhesion to ICAM-1 under flow conditions.

PMID- 12065545
TI  - Mycobacterium tuberculosis CDC1551 is resistant to reactive nitrogen and oxygen
      intermediates in vitro.
AB  - Resistance to reactive oxygen intermediates and reactive nitrogen intermediates
      in vitro of a clinical isolate of Mycobacterium tuberculosis (CDC1551) that
      caused a large outbreak of tuberculosis was compared to that of M. tuberculosis
      strains CB3.3, H37Rv, H37Ra, Erdman, RJ2E, C.C. 13, and C.C. 22 as well as M.
      bovis strains Ravenel and BCG. CDC1551 and CB3.3 were significantly more
      resistant to both hydrogen peroxide (H(2)O(2)) and acidified sodium nitrite than
      were the other strains tested. This biological phenotype may serve as an in vitro
      marker for clinical strains of M. tuberculosis likely to cause a large outbreak
      of tuberculosis.

PMID- 12065546
TI  - Molecular cloning of a vaccine antigen against infection with the larval stage of
      Echinococcus multilocularis.
AB  - Alveolar and cystic hydatidosis are caused by infection with the larval stages of
      Echinococcus multilocularis and Echinococcus granulosus, respectively. A host
      protective antigen has been identified in E. granulosus. Here we identify the
      presence of a closely related protein in E. multilocularis, characterize and
      express a cDNA encoding the antigen (designated EM95), determine the structure of
      the em95 gene, and demonstrate that the EM95 recombinant protein can be used to
      induce significant levels of protection against challenge infection with E.
      multilocularis eggs in mice.

PMID- 12065547
TI  - Activation of the Pseudomonas aeruginosa type III secretion system requires an
      intact pyruvate dehydrogenase aceAB operon.
AB  - Pseudomonas aeruginosa clinical cystic fibrosis isolate CHA was mutagenized with
      Tn5Tc to identify new genes involved in type III secretion system (TTSS)
      dependent cytotoxicity toward human polymorphonuclear neutrophils. Among 25
      mutants affected in TTSS function, 14 contained the insertion at different
      positions in the aceAB operon encoding the PDH-E1 and -E2 subunits of pyruvate
      dehydrogenase. In PDH mutants, no transcriptional activation of TTSS genes in
      response to calcium depletion occurred. Expression in trans of ExsA restored TTSS
      function and cytotoxicity.

PMID- 12065548
TI  - Genome sequence survey identifies unique sequences and key virulence genes with
      unusual rates of amino Acid substitution in bovine Staphylococcus aureus.
AB  - Staphylococcus aureus is a major cause of mastitis in bovine and other ruminant
      species. We here present the results of a comparative genomic analysis between a
      bovine mastitis-associated clone, RF122, and the recently sequenced human
      associated clones, Mu50 and N315, of Staphylococcus aureus. A shotgun sequence
      survey of approximately 10% of the RF122 genome identified numerous unique
      sequences and those with elevated rates of nonsynonymous substitution. Taken
      together, these analyses show that there are notable differences in the genomes
      of bovine mastitis-associated and human clones of S. aureus and provide a
      framework for the identification of specific factors associated with host
      specificity in this major human and animal pathogen.

PMID- 12065549
TI  - Treponema denticola is resistant to human beta-defensins.
AB  - Spirochetes, including Treponema denticola, are implicated in the pathogenesis of
      periodontal disease. Because T. denticola lacks lipopolysaccharides that serve as
      targets for human beta-defensin (h beta D) binding, we postulated that T.
      denticola would resist killing by h beta D. We showed that T. denticola is
      resistant to h beta D-1 and -2. Protease inhibitors did not enhance killing of T.
      denticola by h beta D-2, suggesting that degradation of h beta D-2 by treponemal
      proteases is not a major factor in T. denticola resistance.

PMID- 12065550
TI  - Use of chest computed tomography for staging and treatment of Wilms' tumor in
      children.

PMID- 12065551
TI  - Genetic strategies to individualize supportive care.

PMID- 12065552
TI  - Role of chest computed tomography at diagnosis in the management of Wilms' tumor:
      a study by the United Kingdom Children's Cancer Study Group.
AB  - PURPOSE: This study sought to determine whether the identification of minimal
      pulmonary metastatic disease by chest computed tomography (CT) performed at
      diagnosis in patients with Wilms' tumor and normal chest x-rays (CXR) could
      predict a subgroup of children at increased risk of pulmonary relapse. PATIENTS
      AND METHODS: A retrospective analysis was carried out of the records of 449
      children entered onto the United Kingdom Childrens' Cancer Study Group Second
      Wilms' Tumor Study between July 1986 and September 1991. The imaging protocol did
      not stipulate chest CT at diagnosis, but 141 children who had normal frontal and
      lateral CXRs and a chest CT scan performed at diagnosis were eligible for
      analysis. After surgery, children with stage I Wilms' tumor received single-agent
      chemotherapy (vincristine), whereas children with stages II, III, and bilateral
      Wilms' tumor received combination chemotherapy. Most children with stage III
      tumors were also treated with abdominal radiotherapy (20 Gy). RESULTS: In 31
      patients (22%), pulmonary nodules were visible on chest CT; eight experienced
      relapse, four (15%) in the lungs. When only stage I patients were analyzed, there
      was a significant difference between the pulmonary relapse rate of 43% (three of
      seven) in the CT-positive group and 10% (five of 48) in the CT-negative group (P
      =.02). Four of eight patients with stage I disease with pulmonary relapse died.
      CONCLUSION: CT seemed to identify a subgroup of stage I patients who were at
      increased risk of pulmonary relapse. These children had received only single
      agent chemotherapy. A prospective randomized trial is needed to clarify whether
      these children would benefit from combination chemotherapy.

PMID- 12065553
TI  - Impact of addition of maintenance therapy to intensive induction and
      consolidation chemotherapy for childhood acute myeloblastic leukemia: results of
      a prospective randomized trial, LAME 89/91. Leucamie Aique Myeloide Enfant.
AB  - PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after
      intensive induction and consolidation therapy confers any advantage in childhood
      acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with
      AML were registered in the Leucamie Aique Myeloide Enfant (LAME) 89/91 protocol.
      This regimen included an intensive induction phase (mitoxantrone plus cytarabine)
      and, for patients without allograft, two consolidation courses, one containing
      timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME
      89 pilot study, patients were given an additional MT consisting of mercaptopurine
      and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to
      receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved
      a complete remission. The overall survival and event-free survival at 6 years
      were 60% +/- 6% and 48% +/- 6%, respectively. For the complete responders after
      consolidation therapy, the 5-year disease-free survival was not significantly
      different in MT-negative and in MT-positive randomized patients (respectively,
      60% +/- 19% v 50% +/- 15%; P =.25), whereas the 5-year overall survival was
      significantly better in MT-negative randomized patients (81% +/- 13% v 58% +/-
      15%; P =.04) due to a higher salvage rate after relapse. CONCLUSION: More than
      50% of patients can be cured of AML in childhood. Either drug intensity or each
      of the induction and postremission phases may have contributed to the outstanding
      improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose
      MT may contribute to clinical drug resistance and treatment failure in patients
      who experience relapse.

PMID- 12065554
TI  - Intensive, very short-term chemotherapy for advanced Burkitt's lymphoma in
      children.
AB  - PURPOSE: To improve the 63% event-free survival (EFS) achieved before 1986 in
      Murphy's stage III to IV Burkitt's lymphoma (BL), both chemotherapy and
      supportive care were intensified. PATIENTS AND METHODS: From May 1987 to February
      2001, 60 children, median age 9 years (range, 2.1 to 17 years), with advanced BL
      were enrolled onto two sequential institutional studies. From 1987 to 1992, 30
      patients were stratified according to the absence (regimen IA, n = 19) or
      presence (regimen IB, n = 11) of bone marrow (BM) or CNS involvement. After 5
      week cytoreductive chemotherapy consisting of vincristine, cyclophosphamide,
      doxorubicin, high-dose (HD) methotrexate (MTX), and intrathecal MTX or
      cytarabine, HD cytarabine and cisplatin were provided as a 4-day continuous
      infusion. Regimen IB was intensified by adding etoposide and HD ifosfamide and
      escalating MTX doses. Since 1992, regardless of BM or CNS status, 30 patients
      have been placed on regimen II, which is identical to IB but without ifosfamide.
      The scheduled duration of regimen II was 45 days. RESULTS: EFS and disease-free
      survival at 5 years are 81% +/- 5% and 87% +/- 5%, respectively, for 59
      assessable patients (73% +/- 8% and 85% +/- 7% for regimen IA + IB, 89% +/- 6%,
      EFS and disease-free survival, for regimen II; median follow-up, 6.7 years;
      range, 0.6 to 13.5 years). Six patients, two of whom were receiving regimen II,
      died as a result of initial treatment failure or relapse, and five patients, none
      receiving regimen II, died as a result of treatment-related complications.
      CONCLUSION: This 45-day intensive chemotherapy program is the shortest schedule
      for disseminated BL and overcomes previously recognized risk factors such as BM
      and CNS infiltration.

PMID- 12065555
TI  - Hepatocellular carcinoma in children and adolescents: results from the Pediatric
      Oncology Group and the Children's Cancer Group intergroup study.
AB  - PURPOSE: To determine surgical resectability, event-free survival (EFS), and
      toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment
      with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP
      and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six
      patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098
      (Pediatric Oncology Group (POG) 8945/Children's Cancer Group (CCG) 8881). After
      initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and
      stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or
      regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was
      19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88%
      (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20%
      (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P
      =.78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for
      regimen B when compared with regimen A. Outcome was similar for either regimen
      within disease stages. Events occurred before postinduction surgery I in 18 (47%)
      of 38 patients with stage III or IV disease, and tumor resection was possible in
      two (10%) of the remaining 20 children with advanced-stage disease after
      chemotherapy. CONCLUSION: Children with initially resectable HCC have a good
      prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was
      uniformly poor for children with advanced-stage disease treated with either
      regimen. New therapeutic strategies are needed for the treatment of advanced
      stage pediatric HCC.

PMID- 12065556
TI  - Hepatocellular carcinoma in children: results of the first prospective study of
      the International Society of Pediatric Oncology group.
AB  - PURPOSE: To improve survival and reduce operative morbidity and mortality in
      children with primary epithelial liver tumors by using preoperative chemotherapy,
      as well as to collect information on the epidemiology, natural history, and
      prognostic factors. PATIENTS AND METHODS: Forty children with hepatocellular
      carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors
      International Society of Pediatric Oncology's first study from January 1990 to
      February 1994. The outcome could be analyzed in 39 of those patients. Disease was
      often advanced at the time of diagnosis; metastases were identified in 31% of the
      children and extrahepatic tumor extension, vascular invasion, or both in 39%.
      Multifocal tumors were common (56%). Thirty-three percent of tumors were
      associated with hepatic cirrhosis. All but two patients received preoperative
      chemotherapy (cisplatin and doxorubicin). RESULTS: Partial response was observed
      in 18 (49%) of 37 patients; there was no response or progression in the
      remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty
      patients (51%) never became operable. Overall survival at 5 years was 28%, and
      event-free survival was 17%. Most deaths resulted from tumor progression (26 of
      28). Presence of metastases and pretreatment extent of disease system grouping at
      diagnosis had an adverse influence on overall survival in multivariate analysis.
      CONCLUSION: Survival for pediatric HCC patients is significantly inferior to that
      for children with hepatoblastoma. Complete tumor excision remains the only
      realistic chance of cure, although it is often prevented by advanced disease. The
      presence of metastases is the most potent predictor of poor prognosis. A
      prospective worldwide cooperation in the field of pediatric HCC should be
      encouraged to look for novel therapeutic concepts.

PMID- 12065557
TI  - Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor
      antagonists according to cytochrome P-450 2D6 genotypes.
AB  - PURPOSE: The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has
      substantially reduced, but not eliminated, nausea and vomiting in cancer
      chemotherapy. This study sought to investigate whether efficacy of antiemetic
      treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6
      (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid
      metabolizers of these drugs are at risk of being undertreated. PATIENTS AND
      METHODS: Included in the study were 270 cancer patients receiving their first day
      of chemotherapy. Nausea and vomiting were documented using standardized
      interviews. The intensity of nausea was measured with visual analog scales before
      and twice during the chemotherapy. The relationship between the CYP2D6 genotypes
      and the tropisetron serum concentrations 3 and 6 hours after drug administration
      was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      RESULTS: Genetically defined poor metabolizers had higher serum concentrations of
      tropisetron than all other patients (P <.03). Approximately 30% of all patients
      receiving chemotherapy experienced nausea and vomiting. Genetically defined
      ultrarapid meta-bolizers of CYP2D6 substrates had higher frequency of vomiting
      within the first 4 hours (P <.001) and within the period 5 to 24 hours (P <.03)
      after treatment than all the other patients; the tendency for nausea was similar.
      This difference was more pronounced in patients treated with tropisetron than in
      those treated with ondansetron. CONCLUSION: Antiemetic treatment with tropisetron
      or ondansetron could be improved by adjustment for the CYP2D6 genotype;
      approximately 50 subjects would have to be genotyped to protect one patient from
      severe emesis.

PMID- 12065558
TI  - Superior survival with capecitabine plus docetaxel combination therapy in
      anthracycline-pretreated patients with advanced breast cancer: phase III trial
      results.
AB  - PURPOSE: Docetaxel and capecitabine, a tumor-activated oral fluoropyrimidine,
      show high single-agent efficacy in metastatic breast cancer (MBC) and synergy in
      preclinical studies. This international phase III trial compared efficacy and
      tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in
      anthracycline-pretreated patients with MBC. PATIENTS AND METHODS: Patients were
      randomized to 21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on
      days 1 to 14 plus docetaxel 75 mg/m(2) on day 1 (n = 255) or to docetaxel 100
      mg/m(2) on day 1 (n = 256). RESULTS: Capecitabine/docetaxel resulted in
      significantly superior efficacy in time to disease progression (TTP) (hazard
      ratio, 0.652; 95% confidence interval [CI], 0.545 to 0.780; P =.0001; median, 6.1
      v 4.2 months), overall survival (hazard ratio, 0.775; 95% CI, 0.634 to 0.947; P
      =.0126; median, 14.5 v 11.5 months), and objective tumor response rate (42% v
      30%, P =.006) compared with docetaxel. Gastrointestinal side effects and hand
      foot syndrome were more common with combination therapy, whereas myalgia,
      arthralgia, and neutropenic fever/sepsis were more common with single-agent
      docetaxel. More grade 3 adverse events occurred with combination therapy (71% v
      49%, respectively), whereas grade 4 events were slightly more common with
      docetaxel (31% v 25% with combination). CONCLUSION: The significantly superior
      TTP and survival achieved with the addition of capecitabine to docetaxel 75
      mg/m(2), with the manageable toxicity profile, indicate that this combination
      provides clear benefits over single-agent docetaxel 100 mg/m(2).
      Docetaxel/capecitabine therapy is an important treatment option for women with
      anthracycline-pretreated MBC.

PMID- 12065559
TI  - Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results
      of a phase II trial.
AB  - PURPOSE: Few chemotherapy agents are active in leiomyosarcoma (LMS), particularly
      LMS that has progressed after doxorubicin treatment. We sought to determine the
      response to gemcitabine plus docetaxel among patients with LMS. PATIENTS AND
      METHODS: Patients with unresectable LMS of uterine (n = 29) or other (n = 5)
      primary sites who did not respond to zero to two prior chemotherapy regimens were
      enrolled onto a phase II study of gemcitabine 900 mg/m(2) intravenously (i.v.) on
      days 1 and 8 plus docetaxel 100 mg/m(2) i.v. on day 8 with granulocyte colony
      stimulating factor given subcutaneously on days 9 to 15, delivered every 21 days.
      Patients with prior pelvic radiation received 25% lower doses of both agents.
      Gemcitabine was delivered over 30 or 90 minutes in cycles 1 and 2 and by 90
      minute infusion in all subsequent cycles. Pharmacokinetic studies assessed in
      vivo differences in gemcitabine concentrations with different rates of infusion.
      RESULTS: Thirty-four patients (median age, 55 years; range, 32 to 74 years) have
      enrolled. Fourteen had received prior pelvic radiation. Sixteen of 34 patients
      had progressed after doxorubicin-based therapy; 18 had no prior chemotherapy.
      Among 34 patients, complete response was observed in three patients and partial
      response in 15, for an overall response rate of 53% (95% confidence interval, 35%
      to 70%). Seven patients had stable disease. Fifty percent of patients previously
      treated with doxorubicin responded. Hematologic toxicity was common (neutropenia:
      grade 3, 15%; grade 4, 6%; thrombocytopenia: grade 3, 26%; grade 4, 3%), but
      neutropenic fever (6%) and bleeding events (0%) were rare. The median time to
      progression was 5.6 months (range, 4 to 10 months). CONCLUSION: Gemcitabine plus
      docetaxel is tolerable and highly active in treated and untreated patients with
      LMS.

PMID- 12065560
TI  - Prognostic value of tumoral thymidylate synthase and p53 in metastatic colorectal
      cancer patients receiving fluorouracil-based chemotherapy: phenotypic and
      genotypic analyses.
AB  - PURPOSE: The aim of this multicenter prospective study was to evaluate the role
      of intratumoral parameters related to fluorouracil (FU) sensitivity in 103
      metastatic colorectal cancer patients receiving FU-folinic acid. PATIENTS AND
      METHODS: Liver metastatic biopsy specimens were obtained for all patients and
      primary tumor biopsy specimens for 54 patients. Thymidylate synthase (TS),
      folylpolyglutamate synthetase, and dihydropyrimidine dehydrogenase were measured
      by radioenzymatic assays; TS promoter polymorphism (2R/2R v 2R/3R v 3R/3R) was
      determined by polymerase chain reaction; and p53 protein and mutations were
      analyzed by immunoluminometric assay and denaturing gradient gel electrophoresis,
      respectively. RESULTS: p53 mutations were observed in 56.7% of metastases. TS
      activity was significantly higher in 2R/3R tumors as compared with 2R/2R or
      3R/3R. TS activity in metastasis was the only parameter linked to clinical
      responsiveness (responders exhibited the lower TS, P =.047). Univariate Cox
      analyses demonstrated that TS activity in primary tumor (the greater the TS, the
      poorer the survival; P =.040), TS promoter polymorphism in primary tumor (risk of
      death of 2R/3R v 2R/2R, 2.68; P =.035), and p53 stop mutation in metastasis (risk
      of death of stop mutations v wild type, 3.14; P =.018) were the only significant
      biologic predictors of specific survival. Stepwise analysis did not discriminate
      between TS activity and TS polymorphism. CONCLUSION: Present results confirm the
      value of tumoral TS activity for predicting FU responsiveness, point out the
      importance of detailed p53 mutation analysis for predicting survival, and suggest
      that TS genotype in primary tumor carries a prognostic value similar to that of
      TS activity.

PMID- 12065561
TI  - Oxaliplatin in combination with protracted-infusion fluorouracil and radiation:
      report of a clinical trial for patients with esophageal cancer.
AB  - PURPOSE: To identify a dose and schedule of oxaliplatin (OXP) to be safely
      administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and
      external-beam radiation therapy (XRT) for patients with primary esophageal
      carcinoma (EC). PATIENTS AND METHODS: Eligibility included therapeutically naive
      EC patients with clinical disease stages II, III, or IV. Initial doses and
      schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU
      180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on
      day 8. At completion of cycle 1, eligible patients could undergo an operation or
      begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2.
      Stage IV patients were allowed three cycles in the absence of disease
      progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT)
      encountered in cohorts of three consecutive patients. RESULTS: Thirty-eight
      eligible patients received therapy: 22 noninvasively staged as IV and 16
      noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29
      patients started cycle 2, and 24 patients completed cycle 2. The combined
      modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation.
      No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4
      clinical toxicities were noted in eight patients. After cycle 1, 29 patients
      (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an
      operation with intent to resect the esophagus; five patients (38%) exhibited
      pathologic complete responses. CONCLUSION: OXP 85 mg/m(2) on days 1, 15, and 29
      administered with PI 5-FU and XRT is safe, tolerable, and seems effective against
      primary EC. The role of OXP in multimodality regimens against EC deserves further
      evaluation.

PMID- 12065562
TI  - Efficacy and costs of two forms of stress management training for cancer patients
      undergoing chemotherapy.
AB  - PURPOSE: Professionally administered psychosocial interventions have been shown
      to improve the quality of life of cancer patients undergoing chemotherapy. The
      present study sought to improve access to psychosocial interventions during
      chemotherapy treatment by evaluating the efficacy and costs of a patient self
      administered form of stress management training that requires limited
      professional time or experience to deliver. PATIENTS AND METHODS: Four hundred
      eleven patients about to start chemotherapy were randomly assigned to receive
      usual psychosocial care only, a professionally administered form of stress
      management training, or a patient self-administered form of stress management
      training. Quality-of-life assessments were conducted before randomization and
      before the second, third, and fourth treatment cycles. Intervention costs were
      estimated from both payer and societal perspectives. RESULTS: Compared with
      patients who received usual care only, patients receiving the self-administered
      intervention reported significantly (P < or = .05) better physical functioning,
      greater vitality, fewer role limitations because of emotional problems, and
      better mental health. In contrast, patients who received the professionally
      administered intervention fared no better in terms of quality of life than
      patients receiving usual care only. Costs of the self-administered intervention
      were estimated to be 66% (from a payer perspective) to 68% (from a societal
      perspective) less than the average costs of professionally administered
      psychosocial interventions for patients starting chemotherapy. CONCLUSION:
      Evidence regarding the efficacy and favorable costs of self-administered stress
      management training suggests that this intervention has the potential to greatly
      improve patient access to psychosocial intervention during chemotherapy
      treatment.

PMID- 12065563
TI  - Impact of race on prostate-specific antigen outcome after radical prostatectomy
      for clinically localized adenocarcinoma of the prostate.
AB  - PURPOSE: To compare prostate-specific antigen (PSA) outcome after radical
      prostatectomy (RP) for prostate cancer in African-American and white men using
      previously established risk groups. PATIENTS AND METHODS: Between 1989 and 2000,
      2,036 men (n = 162 African-American men, n = 1,874 white men) underwent RP for
      clinically localized prostate cancer. Using pretreatment PSA, Gleason score,
      clinical T stage, and percentage of positive biopsy specimens, patients were
      stratified into low- and high-risk groups. For each risk group, PSA outcome was
      estimated using the actuarial method of Kaplan and Meier. Comparisons of PSA
      outcome between African-American and white men were made using the log-rank test.
      RESULTS: The median age and PSA level for African-American and white men were 60
      and 62 years old and 8.8 and 7.0 ng/mL, respectively. African-Americans had a
      statistically significant increase in PSA (P =.002), Gleason score (P =.003),
      clinical T stage (P =.004), and percentage of positive biopsy specimens (P =.04)
      at presentation. However, there was no statistical difference in the distribution
      of PSA, clinical T stage, or Gleason score between racial groups in the low- and
      high-risk groups. The 5-year estimate of PSA outcome was 87% in the low-risk
      group for all patients (P =.70) and 28% versus 32% in African-American and white
      patients in the high-risk group (P =.28), respectively. Longer follow-up is
      required to confirm if these results are maintained at 10 years. CONCLUSION: Even
      though African-American men presented at a younger age and with more advanced
      disease compared with white men with prostate cancer, PSA outcome after RP when
      controlled for known clinical predictive factors was not statistically different.
      This study supports earlier screening in African-American men.

PMID- 12065564
TI  - Comparing the costs of radiation therapy and radical prostatectomy for the
      initial treatment of early-stage prostate cancer.
AB  - PURPOSE: Radical prostatectomy and external-beam radiation are the most common
      treatments for localized prostate cancer. Given the absence of clinical consensus
      in favor of one treatment or the other, relative costs may be a significant
      factor. This study compares the direct medical costs during the month before and
      9 months after diagnosis for patients treated primarily with external-beam
      radiation or radical prostatectomy for early-stage prostate cancer. METHODS:
      Patients age 65 or older and coded by the Surveillance, Epidemiology, and End
      Results (SEER) registry as having been diagnosed with adenocarcinoma of the
      prostate treated primarily with external-beam radiation or radical prostatectomy
      during 1992 and 1993 were identified. The initial treatment costs, as measured by
      Medicare-approved payment amounts, for each strategy were analyzed using linked
      SEER-Medicare claims data after adjusting for differences in comorbidity and age.
      An intent-to-treat analysis was also performed to adjust for differences in
      staging between the two groups. RESULTS: For patients in the treatment-received
      analysis, the average costs were significantly different; $14,048 (95% confidence
      interval [CI], $13,765 to $14,330) for radiation therapy and $17,226 (95% CI,
      $16,891 to $17,560) for radical prostatectomy (P <.001). The average costs for
      patients in the intent-to-treat analysis were also significantly less for
      radiation therapy patients ($14,048; 95% CI, $13,765 to $14,330) than for those
      who underwent radical prostatectomy ($17,516; 95% CI, $17,195 to $17,837; P
      <.001). CONCLUSION: For patients with early-stage prostate cancer, average costs
      during the initial treatment interval were at least 23% greater for radical
      prostatectomy than for external-beam radiation. Major limitations of the research
      include not studying costs after the initial treatment interval and questionable
      current applicability, given changes in management of early prostate cancer.

PMID- 12065565
TI  - Trimetrexate in relapsed T-cell lymphoma with skin involvement.
AB  - PURPOSE: Methotrexate (MTX) is active against lymphomas, but transport or
      polyglutamylation mutations confer MTX resistance. Because trimetrexate (TMTX)
      enters cells by passive diffusion and is not polyglutamylated, its activity in
      relapsed T-cell lymphoma was investigated. PATIENTS AND METHODS: Eligible
      patients had histologically confirmed relapsed T-cell lymphoma involving the
      skin, had received more than one previous regimen, were older than 16 years, had
      normal organ function, and had no CNS disease or serious infections, including
      human immunodeficiency virus. TMTX (200 mg/m(2)) was given intravenously every 14
      days without topical or systemic corticosteroids. Patients who responded received
      up to 12 doses. RESULTS: Twenty patients were assessable for response. Median age
      was 59 years (range, 45 to 87 years); 13 patients were men. Three patients had
      anaplastic large-cell lymphoma, 15 had mycosis fungoides or Sezary syndrome (14
      with large-cell transformation), and two had peripheral T-cell lymphoma. Serum
      lactate dehydrogenase was high in 35%, and beta-2 microglobulin was more than 3.0
      mg/L in 35% of patients. The median number of previous regimens was three (range,
      two to 15) and included MTX in five patients. Disease was refractory to the
      regimen immediately preceding TMTX in 85% of patients. Responses were complete in
      one and partial in eight patients (overall response rate, 45%). Two of five
      patients previously treated with MTX responded. Grade 3 or 4 mucositis was
      observed after 4%, infection after 3%, neutropenic fever after 6%, neutrophils
      less than 100/microL after 4%, and platelets less than 10,000/microL after 3% of
      TMTX doses. CONCLUSION: TMTX is active with acceptable toxicity in this
      population and merits further investigation.

PMID- 12065566
TI  - Novel targets for lung cancer therapy: part I.
AB  - Lung cancer is the second most common form of cancer in the United States, and
      although it accounts for 15% of all cancers, it is the most lethal, accounting
      for approximately 28% of cancer deaths. In 2002, it is estimated that 177,000 new
      cases of lung cancer will be diagnosed in the United States, and an estimated
      160,000 men and women will die from the disease. This mortality rate is greater
      than that attributable to colorectal, breast, and prostate cancer combined.
      Systemic treatments for lung cancer with standard chemotherapy agents are still
      relatively ineffective. Agents targeting novel proliferative and survival
      pathways in lung cancer are needed to improve treatment outcomes. In recent
      years, numerous agents inhibiting aberrant processes in tumor cells have
      undergone clinical evaluation. This review is the first of a two-part series that
      summarizes pertinent preclinical and clinical information on novel drugs that
      target critical abnormalities in lung cancer. In this article, agents inhibiting
      growth factor receptors and various molecules downstream of activated signaling
      cascades, such as cytoplasmic second messengers, are described.

PMID- 12065567
TI  - 2002 update of recommendations for the use of chemotherapy and radiotherapy
      protectants: clinical practice guidelines of the American Society of Clinical
      Oncology.

PMID- 12065568
TI  - T helper cell activation in B-cell lymphomas.

PMID- 12065569
TI  - Evaluating neoadjuvant chemotherapy in breast cancer.

PMID- 12065570
TI  - Lack of adherence with the analgesic regimen: the cancer patients' perspective on
      a two-sided problem.

PMID- 12065571
TI  - Neoadjuvant chemotherapy followed by surgery in locally advanced cervical
      carcinoma.

PMID- 12065572
TI  - Comment on "Prognostic factors in high-grade osteosarcoma of the extremities or
      trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative
      Osteosarcoma Study Group protocols".

PMID- 12065573
TI  - Induction chemotherapy and involved-field radiotherapy for intracranial
      germinoma.

PMID- 12065574
TI  - Comparative efficacy of dronabinol and megestrol acetate.

PMID- 12065575
TI  - A critical interplay between Ca2+ inhibition and activation by Mg2+ of AC5
      revealed by mutants and chimeric constructs.
AB  - Adenylyl cyclase type 5 (AC5) is sensitive to both high and low affinity
      inhibition by Ca(2+). This property provides a sensitive feedback mechanism of
      the Ca(2+) entry that is potentiated by cAMP in sources where AC5 is commonly
      expressed (e.g. myocardium). Remarkably little is known about the molecular
      mechanism whereby Ca(2+) inhibits AC5. Because previous studies had showed that
      Ca(2+) antagonized the activation of adenylyl cyclase brought about by Mg(2+), we
      have now evaluated the Mg(2+)-binding domain in the catalytic site as the
      potential site of the interaction, using a number of mutations of AC5 with
      impaired Mg(2+) activation. Mg(2+) activation exerted contrasting effects on the
      high and low affinity Ca(2+) inhibition. In both wild type and mutants,
      activation by Mg(2+) decreased the absolute amount of high affinity inhibition
      without affecting the K(i) value, whereas the K(i) value for low affinity
      inhibition was decreased. These effects were directly proportional to the
      sensitivity of the mutants to Mg(2+). Parallel changes were noted in the
      efficacies of Ca(2+), Sr(2+), and Ba(2+) in the mutant species, suggesting a
      simple mutation in a shared domain. Strikingly, forskolin, which activates by a
      mechanism different from Mg(2+), did not modify inhibition by Ca(2+). Deletion of
      the N terminus and the C1b domain of AC5 and a chimera formed with AC2 confirmed
      that the catalytic domain alone was responsible for high affinity inhibition. We
      therefore conclude that both low and high affinity inhibition by Ca(2+) are
      exerted on different conformations of the Mg(2+)-binding sites in the catalytic
      domain of AC5.

PMID- 12065576
TI  - Intracellular assembly of very low density lipoproteins containing apolipoprotein
      B100 in rat hepatoma McA-RH7777 cells.
AB  - Previous studies with McA-RH7777 cells showed a 15-20-min temporal delay in the
      oleate treatment-induced assembly of very low density lipoproteins (VLDL) after
      apolipoprotein (apo) B100 translation, suggesting a post-translational process.
      Here, we determined whether the post-translational assembly of apoB100-VLDL
      occurred within the endoplasmic reticulum (ER) or in post-ER compartments using
      biochemical and microscopic techniques. At steady state, apoB100 distributed
      throughout ER and Golgi, which were fractionated by Nycodenz gradient
      centrifugation. Pulse-chase experiments showed that it took about 20 min for
      newly synthesized apoB100 to exit the ER and to accumulate in the cis/medial
      Golgi. At the end of a subsequent 20-min chase, a small fraction of apoB100
      accumulated in the distal Golgi, and a large amount of apoB100 was secreted into
      the medium as VLDL. VLDL was not detected either in the lumen of ER or in that of
      cis/medial Golgi where apoB100 was membrane-associated and sensitive to
      endoglycosidase H treatment. In contrast, VLDL particles were found in the lumen
      of the distal Golgi where apoB100 was resistant to endoglycosidase H. Formation
      of lumenal VLDL almost coincided with the appearance of VLDL in the medium,
      suggesting that the site of VLDL assembly is proximal to the site of secretion.
      When microsomal triglyceride transfer protein activity was inactivated after apoB
      had exited the ER, VLDL formation in the distal Golgi and its subsequent
      secretion was unaffected. Lipid analysis by tandem mass spectrometry showed that
      oleate treatment increased the masses of membrane phosphatidylcholine (by 68%)
      and phosphatidylethanolamine (by 27%) and altered the membrane phospholipid
      profiles of ER and Golgi. Taken together, these results suggest that VLDL
      assembly in McA-RH7777 cells takes place in compartments at the distal end of the
      secretory pathway.

PMID- 12065577
TI  - Involvement of cell-cell interactions in the rapid stimulation of Cas tyrosine
      phosphorylation and Src kinase activity by transforming growth factor-beta 1.
AB  - Transforming growth factor-beta (TGF-beta) regulates a wide range of
      physiological and pathological cellular processes, including cell migration,
      mesenchymal transition, extracellular matrix synthesis, and cell death. Cas (Crk
      associated substrate, 130 kDa), an adaptor protein localized at focal adhesions
      and stress fibers, is also known to have important functions in cell migration
      and the induction of immediate-early gene expression. Here, we report that a
      rapid and transient tyrosine phosphorylation of Cas is induced by TGF-beta 1 and
      that E-cadherin-mediated cell-cell interaction and the Src kinase pathway are
      involved in this early TGF-beta signaling. The addition of TGF-beta 1 to
      epithelial cells rapidly induced tyrosine phosphorylation of Cas and promoted the
      formation of complexes between focal adhesion molecules. Cas phosphorylation
      required the integrity of the actin cytoskeleton but was not dependent on cell
      adhesion, implying that Cas-dependent signaling may be distinct from integrin
      signaling. TGF-beta 1 also stimulated Src kinase activity, and specific
      inhibitors of Src completely blocked the induction of Cas phosphorylation by TGF
      beta 1. The Cas phosphorylation and Src kinase activation seen in our results
      were induced in an epithelial phenotype-specific manner. Stable transfection of E
      cadherin to L929 cells and L cells as well as E-cadherin blocking assay revealed
      that E-cadherin-mediated cell-cell interactions were essential for both Cas
      phosphorylation and Src kinase activation. Taken together, our data suggest that
      rapid Cas phosphorylation and Src kinase activation may play a novel role in TGF
      beta signal transduction.

PMID- 12065578
TI  - Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate
      acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in
      rat tissues in response to exercise.
AB  - Changes in the concentration of malonyl-CoA in many tissues have been related to
      alterations in the activity of acetyl-CoA carboxylase (ACC), the rate-limiting
      enzyme in its formation. In contrast, little is known about the physiological
      role of malonyl-CoA decarboxylase (MCD), an enzyme responsible for malonyl-CoA
      catabolism. In this study, we examined the effects of voluntary exercise on MCD
      activity in rat liver, skeletal muscle, and adipose tissue. In addition, the
      activity of sn-glycerol-3-phosphate acyltransferase (GPAT), which like MCD and
      ACC can be regulated by AMP-activated protein kinase (AMPK), was assayed. Thirty
      min after the completion of a treadmill run, MCD activity was increased
      approximately 2-fold, malonyl-CoA levels were reduced, and ACC and GPAT
      activities were diminished by 50% in muscle and liver. These events appeared to
      be mediated via activation of AMPK since: 1) AMPK activity was concurrently
      increased by exercise in both tissues; 2) similar findings were observed after
      the injection of 5-amino 4 imidazole carboxamide, an AMPK activator; 3) changes
      in the activity of GPAT and ACC paralleled that of MCD; and 4) the increase in
      MCD activity in muscle was reversed in vitro by incubating immunoprecipitated
      enzyme from the exercised muscle with protein phosphatase 2A, and it was
      reproduced by incubating immunopurified MCD from resting muscle with purified
      AMPK. An unexpected finding was that exercise caused similar changes in the
      activities of ACC, MCD, GPAT, and AMPK and the concentration of malonyl-CoA in
      adipose tissue. IN CONCLUSION: MCD, GPAT, and ACC are coordinately regulated by
      AMPK in liver and adipose tissue in response to exercise, and except for GPAT,
      also in muscle. The results suggest that AMPK activation plays a major role in
      regulating lipid metabolism in many cells following exercise. They also suggest
      that in each of them, it acts to increase fatty acid oxidation and decrease its
      esterification.

PMID- 12065579
TI  - Genetic analysis of GalR tetramerization in DNA looping during repressosome
      assembly.
AB  - The Gal repressosome is a nucleoprotein complex consisting of 2 GalR dimers, 1
      HU, and 1 DNA loop, which represses the transcription of the gal operon. We have
      adopted a structure-based genetic approach to complement ongoing physical studies
      of the complex. Homology-based and subsequent alanine-scanning mutageneses
      suggest that five residues in the DNA-distal subdomain of GalR dimer are
      important for repressosome formation. A further analysis of these and intragenic
      suppressors of looping-defective GalR mutants as well as gain-of-function mutants
      that permit repressosome assembly in the absence of HU show that GalR dimers
      contact each other in the repressosome in a partially stacked configuration.

PMID- 12065580
TI  - Separation and characterization of late endosomal membrane domains.
AB  - Very little is known about the biophysical properties and the lipid or protein
      composition of membrane domains presumably present in endocytic and biosynthetic
      organelles. Here we analyzed the membrane composition of late endosomes by
      suborganellar fractionation in the absence of detergent. We found that the
      internal membranes of this multivesicular organelle can be separated from the
      limiting membrane and that each membrane population exhibited a defined
      composition. Our data also indicated that internal membranes may consist of at
      least two populations, containing primarily phosphatidylcholine or
      lysobisphosphatidic acid as major phospholipid, arguing for the existence of
      significant microheterogeneity within late endosomal membranes. We also found
      that lysobisphosphatidic acid exhibited unique pH-dependent fusogenic properties,
      and we speculated that this lipid is an ideal candidate to regulate the dynamic
      properties of this internal membrane mosaic.

PMID- 12065581
TI  - A novel candidate for the true fructose-1,6-bisphosphatase in archaea.
AB  - Fructose-1,6-bisphosphatase (FBPase) is one of the key enzymes of the
      gluconeogenic pathway. Although enzyme activity had been detected in Archaea, the
      corresponding gene had not been identified until a presumable inositol
      monophosphatase gene from Methanococcus jannaschii was found to encode a protein
      with both inositol monophosphatase and FBPase activities. Here we display that a
      gene from the hyperthermophilic archaeon, Thermococcus kodakaraensis KOD1, which
      does not correspond to the inositol monophosphatase gene from M. jannaschii,
      displays high FBPase activity. The FBPase from strain KOD1 was partially
      purified, its N-terminal amino acid sequence was determined, and the gene (Tk
      fbp) was cloned. Tk-fbp encoded a protein of 375 amino acid residues with a
      molecular mass of 41,658 Da. The recombinant Tk-Fbp was purified and
      characterized. Tk-Fbp catalyzed the conversion of fructose 1,6-bisphosphate to
      fructose 6-phosphate following Michaelis-Menten kinetics with a K(m) value of 100
      microm toward fructose 1,6-bisphosphate, and a k(cat) value of 17 s(-1) subunit(
      1) at 95 degrees C. Unlike the inositol monophosphatase from M. jannaschii, Tk
      Fbp displayed strict substrate specificity for fructose 1,6-bisphosphate.
      Activity was enhanced by Mg(2+) and dithioerythritol, and was slightly inhibited
      by fructose 2,6-bisphosphate. AMP did not inhibit the enzyme activity. We
      examined whether expression of Tk-fbp was regulated at the transcription level.
      High levels of Tk-fbp transcripts were detected in cells grown on pyruvate or
      amino acids, whereas no transcription was detected when starch was present in the
      medium. Orthologue genes corresponding to Tk-fbp with high similarity are present
      in all the complete genome sequences of thermophilic Archaea, including M.
      jannaschii, Pyrococcus furiosus, Sulfolobus solfataricus, and Archaeoglobus
      fulgidus, but are yet to be assigned any function. Taking into account the high
      FBPase activity of the protein, the strict substrate specificity, and its sugar
      repressed gene expression, we propose that Tk-Fbp may represent the bona fide
      FBPase in Archaea.

PMID- 12065582
TI  - Distinct kinetics for binding of the CD46 and SLAM receptors to overlapping sites
      in the measles virus hemagglutinin protein.
AB  - Measles virus (MV) is a human pathogen using two distinct cell surface receptors
      for entry into host cells. We present here a comparative analysis for binding of
      the MV receptors CD46 and SLAM to the measles virus hemagglutinin protein (MVH,
      Edmonston strain). Soluble monomeric and dimeric MVH variants were prepared in
      mammalian cells and their conformation assessed using a panel of monoclonal
      antibodies. The two receptor molecules specifically bound to the MVH protein with
      distinct binding modes. The association rate (k(a)) for SLAM binding to MVH was
      very low ( approximately 3000 m(-1)s(-1)), about 20 times lower that the k(a)
      determined for CD46 binding. However, SLAM bound tighter to the virus protein
      than CD46, as revealed by a 5-fold lower dissociation rate (k(d), approximately
      1.5 x 10(-3) s(-1)). These data suggest that the SLAM receptor binds to a less
      accessible and more hydrophobic surface on MVH than the CD46 receptor, as
      illustrated in a binding model. Despite the differences in kinetics, receptor
      competition binding experiments revealed that they recognize overlapping sites in
      MVH. Indeed, a panel of anti-MVH monoclonal antibodies equally inhibited binding
      of both receptor molecules. The similar immune reactivity of the two receptor
      binding sites suggests that the shift in receptor usage by MV may not be driven
      by immune responses.

PMID- 12065583
TI  - Identification of a novel human eicosanoid receptor coupled to G(i/o).
AB  - We have conducted an in silico data base search for and cloned a novel G-protein
      coupled receptor (GPCR) named TG1019. Dot and Northern blotting analyses showed
      that transcripts of the novel GPCR were expressed in various tissues except
      brain, and the expression was more intense in liver, kidney, peripheral
      leukocyte, lung, and spleen than in other tissues. By GTP gamma S binding assay
      using the TG1019-G alpha(i1)-protein fusion expressed in insect cells,
      eicosanoids, and polyunsaturated fatty acids such as 5-oxo-6E,8Z,11Z,14Z
      eicosatetraenoic acid (5-oxo-ETE), 5(S)-hydroperoxy-6E,8Z, 11Z,14Z
      eicosatetraenoic acid, and arachidonic acid were identified to exhibit agonistic
      activities against TG1019. 5-oxo-ETE was the most potent to enhance the specific
      binding by 6-fold at a maximum effect dose of submicromolar to micromolar order
      with an ED(50) value of 5.7 nM. Conversely, polyunsaturated fatty acids such as
      docosahexaenoic acid and eicosapentaenoic acid showed antagonistic activities
      against TG1019. In Chinese hamster ovary cells transiently expressing TG1019, the
      forskolin-stimulated production of cAMP was inhibited up to approximately 70% by
      5-oxo-ETE, with an IC(50) value of 33 nM. This inhibition was sensitive to
      pretreatment of the cells with pertussis toxin.

PMID- 12065584
TI  - Two parallel pathways mediate cytoplasmic localization of the dioxin (aryl
      hydrocarbon) receptor.
AB  - The dioxin receptor is a ligand-dependent transcription factor that mediates the
      biological effects of dioxin and related environmental pollutants. In the absence
      of ligand the receptor is present in the cytoplasmic compartment of the cell
      associated with the hsp90-dependent chaperone complex. This complex regulates
      several functions of the receptor such as ligand binding and nuclear import.
      Furthermore, intracellular localization of the receptor is modulated by multiple
      factors such as the export protein CRM-1 and the hsp90-associated immunophilin
      XAP-2. We have identified the mechanism of XAP-2-induced cytoplasmic localization
      of the receptor and studied the potential cross-talk between CRM-1 and XAP-2. We
      show that XAP-2 anchors the ligand-free receptor to cytoskeletal structures. This
      effect is blocked upon treatment with the actin inhibitor cytochalasin B, whereas
      the tubulin inhibitor colchicine had no effect on receptor localization. In
      addition, we show that the receptor interacts with CRM-1 both in the presence and
      absence of ligand. CRM-1-mediated nuclear export occurs independently of XAP-2.
      Our data provide evidence that CRM-1 and XAP-2 act in parallel through different
      mechanisms and target different interfaces of the receptor. These results suggest
      that two pathways cooperate to localize the non-activated receptor in the
      cytoplasmic compartment of the cell.

PMID- 12065585
TI  - Structural plasticity and noncovalent substrate binding in the GroEL apical
      domain. A study using electrospay ionization mass spectrometry and fluorescence
      binding studies.
AB  - Advances in understanding how GroEL binds to non-native proteins are reported.
      Conformational flexibility in the GroEL apical domain, which could account for
      the variety of substrates that GroEL binds, is illustrated by comparison of
      several independent crystallographic structures of apical domain constructs that
      show conformational plasticity in helices H and I. Additionally, ESI-MS indicates
      that apical domain constructs have co-populated conformations at neutral pH. To
      assess the ability of different apical domain conformers to bind co-chaperone and
      substrate, model peptides corresponding to the mobile loop of GroES and to helix
      D from rhodanese were studied. Analysis of apical domain-peptide complexes by ESI
      MS indicates that only the folded or partially folded apical domain conformations
      form complexes that survive gas phase conditions. Fluorescence binding studies
      show that the apical domain can fully bind both peptides independently. No
      competition for binding was observed, suggesting the peptides have distinct
      apical domain-binding sites. Blocking the GroES-apical domain-binding site in
      GroEL rendered the chaperonin inactive in binding GroES and in assisting the
      folding of denatured rhodanese, but still capable of binding non-native proteins,
      supporting the conclusion that GroES and substrate proteins have, at least
      partially, distinct binding sites even in the intact GroEL tetradecamer.

PMID- 12065586
TI  - Identification and characterization of Gemin7, a novel component of the survival
      of motor neuron complex.
AB  - The survival of motor neurons (SMN) protein is the product of the gene mutated or
      deleted in the neurodegenerative disease, spinal muscular atrophy. SMN is part of
      a large macromolecular complex that also contains Gemin2, Gemin3, Gemin4, Gemin5,
      and Gemin6. The SMN complex functions in the assembly of spliceosomal small
      nuclear ribonucleoproteins and probably other ribonucleoprotein particles. We
      have identified a novel protein component of the SMN complex termed Gemin7 using
      native purified SMN complexes and peptide sequencing by mass spectrometry.
      Coimmunoprecipitation and immunolocalization experiments demonstrate that Gemin7
      is a component of the SMN complex and colocalizes with SMN in the cytoplasm and
      in gems. Binding experiments show that Gemin7 interacts directly with SMN and
      Gemin6 and mediates the association of Gemin6 with the SMN complex. The amino
      acid sequence of Gemin7 does not contain any recognizable motifs with the
      exception of several arginine and glycine repeats that are necessary for its
      interaction with SMN. Moreover, Gemin7 interacts with several Sm proteins of
      spliceosomal small nuclear ribonucleoproteins, in particular, with SmE. With the
      identification of Gemin7, the inventory of the core components of the SMN complex
      appears essentially complete.

PMID- 12065587
TI  - The Saccharomyces cerevisiae nucleoporin Nup2p is a natively unfolded protein.
AB  - Little is known about the structure of the individual nucleoporins that form
      eukaryotic nuclear pore complexes (NPCs). We report here in vitro physical and
      structural characterizations of a full-length nucleoporin, the Saccharomyces
      cerevisiae protein Nup2p. Analyses of the Nup2p structure by far-UV circular
      dichroism (CD) spectroscopy, Fourier transform infrared (FTIR) spectroscopy,
      protease sensitivity, gel filtration, and sedimentation velocity experiments
      indicate that Nup2p is a "natively unfolded protein," belonging to a class of
      proteins that exhibit little secondary structure, high flexibility, and low
      compactness. Nup2p possesses a very large Stokes radius (79 A) in gel filtration
      columns, sediments slowly in sucrose gradients as a 2.9 S particle, and is highly
      sensitive to proteolytic digestion by proteinase K; these characteristics suggest
      a structure of low compactness and high flexibility. Spectral analyses (CD and
      FTIR spectroscopy) provide additional evidence that Nup2p contains extensive
      regions of structural disorder with comparatively small contributions of ordered
      secondary structure. We address the possible significance of natively unfolded
      nucleoporins in the mechanics of nucleocytoplasmic trafficking across NPCs.

PMID- 12065588
TI  - A novel site on gamma 3 subunits important for assembly of GABA(A) receptors.
AB  - Gamma-aminobutyric acid, type A (GABA(A)) receptors are ligand-gated chloride
      channels and are the major inhibitory transmitter receptors in the central
      nervous system. The majority of these receptors is composed of two alpha, two
      beta, and one gamma subunits. To identify sequences important for subunit
      assembly, we generated C-terminally truncated and chimeric gamma(3) constructs.
      From their ability to associate with full-length alpha(1) and beta(3) subunits,
      we concluded that amino acid sequence gamma(3)(70-84) either directly interacts
      with alpha(1) or beta(3) subunits or stabilizes a contact site elsewhere in the
      protein. The observation that this sequence contains amino acid residues
      homologous to gamma(2) residues contributing to the benzodiazepine-binding site
      at the alpha(1)/gamma(2) interface suggested that in alpha(1)beta(3)gamma(3)
      receptors the sequence gamma(3)(70-84) is located at the alpha(1)/gamma(3)
      interface. In the absence of alpha(1) subunits this sequence might allow assembly
      of beta(3) with gamma(3) subunits. Other experiments indicated that sequences
      gamma(3)(86-95) and gamma(3)(94-107), which are homologous to previously
      identified sequences important for assembly of gamma(2) subunits, are also
      important for assembly of gamma(3) subunits. This indicates that during assembly
      of the GABA(A) receptor, more than one N-terminal sequence is important for
      binding to the same neighboring subunit. Whether the three sequences investigated
      are involved in direct interaction or stabilize other regions involved in
      intersubunit contacts has to be further studied.

PMID- 12065589
TI  - Age increases cardiac Galpha(i2) expression, resulting in enhanced coupling to G
      protein-coupled receptors.
AB  - Cardiac G protein-coupled receptors that function through stimulatory G protein
      Galpha(s), such as beta(1)- and beta(2)-adrenergic receptors (beta(1)ARs and
      beta(2)ARs), play a key role in cardiac contractility. Recent data indicate that
      several Galpha(s)-coupled receptors in heart also activate Galpha(i), including
      beta(2)ARs (but not beta(1)ARs). Coupling of cardiac beta(2)ARs to Galpha(i)
      inhibits adenylyl cyclase and opposes beta(1)AR-mediated apoptosis. Dual coupling
      of beta(2)AR to both Galpha(s) and Galpha(i) is likely to alter beta(2)AR
      function in disease, such as congestive heart failure in which Galpha(i) levels
      are increased. Indeed, heart failure is characterized by reduced responsiveness
      of betaARs. Cardiac betaAR-responsiveness is also decreased with aging. However,
      whether age increases cardiac Galpha(i) has been controversial, with some studies
      reporting an increase and others reporting no change. The present study examines
      Galpha(i) in left ventricular membranes from young and old Fisher 344 rats by
      employing a comprehensive battery of biochemical assays. Immunoblotting reveals
      significant increases with age in left ventricular Galpha(i2), but no changes in
      Galpha(i3), Galpha(o), Galpha(s), Gbeta(1), or Gbeta(2). Aging also increases ADP
      ribosylation of pertussis toxin-sensitive G proteins. Consistent with these
      results, basal as well as receptor-mediated incorporation of photoaffinity label
      [(32)P]azidoanilido-GTP indicates higher amounts of Galpha(i2) in older left
      ventricular membranes. Moreover, both basal and receptor-mediated adenylyl
      cyclase activities are lower in left ventricular membranes from older rats, and
      disabling of Galpha(i) with pertussis toxin increases both basal and receptor
      stimulated adenylyl cyclase activity. Finally, age produces small but significant
      increases in muscarinic potency for the inhibition of both beta(1)AR- and
      beta(2)AR-stimulated adenylyl cyclase activity. The present study establishes
      that Galpha(i2) increases with age and provides data indicating that this
      increase dampens adenylyl cyclase activity.

PMID- 12065590
TI  - Specificity of the stimulatory interaction between chromosomal HMGB proteins and
      the transcription factor Dof2 and its negative regulation by protein kinase CK2
      mediated phosphorylation.
AB  - The high mobility group (HMG) proteins of the HMGB family are chromatin
      associated proteins that can contribute to transcriptional control by interaction
      with certain transcription factors. Using the transcription factor Dof2 and five
      different maize HMGB proteins, we have examined the specificity of the HMGB
      transcription factor interaction. The HMG-box DNA binding domain of HMGB1 is
      sufficient for the interaction with Dof2. Although all tested HMGB proteins can
      interact with Dof2, the various HMGB proteins stimulate the binding of Dof2 to
      its DNA target site with different efficiencies. The HMGB5 protein is clearly the
      most potent facilitator of Dof2 DNA binding. Maximal stimulation of the DNA
      binding by the HMGB proteins requires association of HMGB and Dof2 prior to DNA
      binding. HMGB5 and Dof2 form a ternary complex with the DNA, but within the
      protein-DNA complex the interaction of HMGB5 and Dof2 is different from that in
      solution, as in contrast to the proteins in solution, they cannot be cross-linked
      with glutaraldehyde when bound to DNA. Phosphorylation of HMGB1 by protein kinase
      CK2 abolishes the interaction with Dof2 and the stimulation of Dof2 DNA binding.
      These findings indicate that transcription factors may recruit certain members of
      the HMGB family as assistant factors.

PMID- 12065591
TI  - Active caspase-8 translocates into the nucleus of apoptotic cells to inactivate
      poly(ADP-ribose) polymerase-2.
AB  - Caspase-8 is the prototypic initiator of the death domain receptor pathway of
      apoptosis. Here, we report that caspase-8 not only triggers and amplifies the
      apoptotic process at cytoplasmic sites but can also act as an executioner at
      nuclear levels. In a murine model of acute ischemia, caspase-8 is relocated into
      the nucleus of apoptotic neurons, where it cleaves PARP-2, a member of the
      poly(ADP-ribose) polymerase family involved in DNA repair. As indicated by site
      directed mutagenesis, PARP-2 cleavage occurs preferentially at the LQMD sequence
      mapped between the DNA binding and the catalytic domains of the protein. This is
      close to the cleavage sequence found in Bid, the cytoplasmic target of caspase-8.
      Activity assays confirm that cleavage of PARP-2 results in inactivation of its
      poly(ADP-ribosylation) property, proportional to the efficiency of the cleavage.
      Our findings add to the complexity of proteolytic caspase networks by
      demonstrating that caspase-8 is in turn an initiator, amplifier, and effector
      caspase.

PMID- 12065592
TI  - Steroid ligands bind human sex hormone-binding globulin in specific orientations
      and produce distinct changes in protein conformation.
AB  - The amino-terminal laminin G-like domain of human sex hormone-binding globulin
      (SHBG) contains a single high affinity steroid-binding site. Crystal structures
      of this domain in complex with several different steroid ligands have revealed
      that estradiol occupies the SHBG steroid-binding site in an opposite orientation
      when compared with 5 alpha-dihydrotestosterone or C19 androgen metabolites (5
      alpha-androstan-3 beta,17 beta-diol and 5 alpha-androstan-3 beta,17 alpha-diol)
      or the synthetic progestin levonorgestrel. Substitution of specific residues
      within the SHBG steroid-binding site confirmed that Ser(42) plays a key role in
      determining high affinity interactions by hydrogen bonding to functional groups
      at C3 of the androstanediols and levonorgestrel and the hydroxyl at C17 of
      estradiol. Among residues participating in the hydrogen bond network with hydroxy
      groups at C17 of C19 steroids or C3 of estradiol, Asp(65) appears to be the most
      important. The different binding mode of estradiol is associated with a
      difference in the position/orientation of residues (Leu(131) and Lys(134)) in the
      loop segment (Leu(131)-His(136)) that covers the steroid-binding site as well as
      others (Leu(171)-Lys(173) and Trp(84)) on the surface of human SHBG and may
      provide a basis for ligand-dependent interactions between SHBG and other
      macromolecules. These new crystal structures have also enabled us to construct a
      simple space-filling model that can be used to predict the characteristics of
      novel SHBG ligands.

PMID- 12065593
TI  - Beta-arrestin binding to CC chemokine receptor 5 requires multiple C-terminal
      receptor phosphorylation sites and involves a conserved Asp-Arg-Tyr sequence
      motif.
AB  - Agonist binding to the CC chemokine receptor 5 (CCR5) induces the phosphorylation
      of four distinct serine residues that are located in the CCR5 C terminus. We
      established a series of clonal RBL-2H3 cell lines expressing CCR5 with alanine
      mutations of Ser(336), Ser(337), Ser(342), and Ser(349) in various combinations
      and explored the significance of phosphorylation sites for the ability of the
      receptor to interact with beta-arrestins and to undergo desensitization and
      internalization upon ligand binding. Receptor mutants that lack any two
      phosphorylation sites retained their ability to recruit endogenous beta-arrestins
      to the cell membrane and were normally sequestered, whereas alanine mutation of
      any three C-terminal serine residues abolished both beta-arrestin binding and
      rapid agonist-induced internalization. In contrast, RANTES (regulated on
      activation normal T cell expressed and secreted) stimulation of a S336A/S349A
      mutant triggered a sustained calcium response and enhanced granular enzyme
      release. This mutational analysis implies that CCR5 internalization largely
      depends on a beta-arrestin-mediated mechanism that requires the presence of any
      two phosphorylation sites, whereas receptor desensitization is independently
      regulated by the phosphorylation of distinct serine residues. Surface plasmon
      resonance analysis further demonstrated that purified beta-arrestin 1 binds to
      phosphorylated and nonphosphorylated C-tail peptides with similar affinities,
      suggesting that beta-arrestins use additional receptor sites to discriminate
      between nonactivated and activated receptors. Surface plasmon resonance analysis
      revealed beta-arrestin 1 binding to the second intracellular loop of CCR5, which
      required an intact Asp-Arg-Tyr triplet. These results suggest that a conserved
      sequence motif within the second intracellular loop of CCR5 that is known to be
      involved in G protein activation plays a significant role in beta-arrestin
      binding to CCR5.

PMID- 12065594
TI  - Caspase-2 acts upstream of mitochondria to promote cytochrome c release during
      etoposide-induced apoptosis.
AB  - DNA damage induced by the cancer chemotherapeutic drug etoposide triggers the
      onset of a series of intracellular events characteristic of apoptosis. Among the
      early changes observed is the release of cytochrome c from mitochondria, although
      the mechanism responsible for this effect is unclear. We demonstrate here a role
      for caspase-2 in etoposide-induced cytochrome c release. In particular, Jurkat T
      lymphocytes treated with an irreversible caspase-2 inhibitor, benzyloxycarbonyl
      Val-Asp-Val-Ala-Asp-fluoromethyl ketone (z-VDVAD-fmk), or stably transfected with
      pro-caspase-2 antisense (Casp-2/AS) are refractory to cytochrome c release
      stimulated by etoposide. Experiments performed using a reconstituted cell-free
      system indicate that etoposide-induced cytochrome c release by way of caspase-2
      occurs independently of cytosolic factors, suggesting that the nuclear pool of
      pro-caspase-2 is critical to this process. Apart from inhibiting cytochrome c
      release, undermining caspase-2 activity results in an attenuation of downstream
      events, such as pro-caspase-9 and -3 activation, phosphatidylserine exposure on
      the plasma membrane, and DNA fragmentation. Taken together, our data indicate
      that caspase-2 provides an important link between etoposide-induced DNA damage
      and the engagement of the mitochondrial apoptotic pathway.

PMID- 12065596
TI  - Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer
      of cumulus cells and fertilize the egg.
AB  - The function of glycosylphosphatidylinositol-anchored sperm hyaluronidase PH-20
      in fertilization has long been believed to enable acrosome-intact sperm to pass
      through the layer of cumulus cells and reach the egg zona pellucida. In this
      study, we have produced mice carrying a null mutation in the PH-20 gene using
      homologous recombination. Despite the absence of sperm PH-20, the mutant male
      mice were still fertile. In vitro fertilization assays showed that mouse sperm
      lacking PH-20 possess a reduced ability to disperse cumulus cells from the
      cumulus mass, resulting in delayed fertilization solely at the early stages after
      insemination. Moreover, SDS-PAGE of sperm extracts and subsequent Western blot
      analysis revealed the presence of other hyaluronidase(s), except PH-20,
      presumably within the acrosome of mouse sperm. These data provide evidence that
      PH-20 is not essential for fertilization, at least in the mouse, suggesting that
      the other hyaluronidase(s) may play an important role in sperm penetration
      through the cumulus cell layer and/or the egg zona pellucida, possibly in
      cooperation with PH-20, although the importance of sperm motility cannot be
      neglected.

PMID- 12065597
TI  - Characterization of iron-sulfur protein assembly in isolated mitochondria. A
      requirement for ATP, NADH, and reduced iron.
AB  - To study the biochemical requirements for maturation of iron-sulfur (Fe/S)
      proteins, we have reconstituted the process in vitro using detergent extracts
      from Saccharomyces cerevisiae mitochondria. Efficient assembly of biotin synthase
      as a model Fe/S protein required anaerobic conditions, dithiothreitol, cysteine,
      ATP, and NADH. Cysteine is utilized by the cysteine desulfurase Nfs1p to release
      sulfan sulfur; ATP presumably reflects the function of the Hsp70 family chaperone
      Ssq1p; and NADH is used for reduction of the ferredoxin Yah1p involved in Fe/S
      protein biogenesis. Hence, our assay system faithfully reproduces the in vivo
      pathway. We have further investigated the involvement of various mitochondrial
      proteins suspected to participate in Fe/S protein biogenesis. In mitochondrial
      extracts depleted in Isa1p, Fe/S protein formation was severely decreased. A
      similar strong decline was observed with extracts from Delta yfh1 mitochondria,
      indicating that both Isa1p and the yeast frataxin homologue, Yfh1p, are crucial
      for biogenesis of mitochondrial Fe/S proteins. Conversely, the activities of
      mitochondrial extracts from Delta nfu1 cells were only moderately reduced,
      suggesting a dispensable role for Nfu1p. Finally, iron utilized for Fe/S protein
      formation was imported into the matrix of intact mitochondria in ferrous form in
      a membrane potential-dependent transport step. Our results represent the first in
      vitro reconstitution of the entire pathway of Fe/S protein maturation.

PMID- 12065595
TI  - A role for phosphorylation of inositol 1,4,5-trisphosphate receptors in defining
      calcium signals induced by Peptide agonists in pancreatic acinar cells.
AB  - Stimulation of pancreatic acinar cells with acetylcholine (ACh) and
      cholecystokinin (CCK) results in an elevation of cytosolic calcium ([Ca(2+)](c))
      through activation of inositol 1,4,5-trisphosphate receptors (InsP(3)R). The
      global temporal pattern of the [Ca(2+)](c) changes produced by ACh or CCK
      stimulation differs significantly. The hypothesis was tested that CCK stimulation
      results in a protein kinase A (PKA)-mediated phosphorylation of InsP(3)R and this
      event contributes to the generation of agonist-specific [Ca(2+)](c) signals.
      Physiological concentrations of CCK evoked phosphorylation of the type III
      InsP(3)R, which was blocked by pharmacological inhibition of PKA. Imaging of fura
      2-loaded acinar cells revealed that the rate of [Ca(2+)](c) rise during CCK
      evoked oscillations slows with each subsequent oscillation, consistent with a
      developing modulation of release, whereas the kinetics of ACh-evoked oscillations
      remain constant. Stimulation of cells with ACh following activation of PKA
      resulted in a slowing of the ACh-evoked [Ca(2+)](c) rise, which now resembled a
      time-matched CCK response. PKA activation also resulted in a slowing of
      [Ca(2+)](c) increases elicited by photolysis of caged InsP(3). Targeted, PKA
      mediated phosphorylation of type III InsP(3)R is involved in a physiological CCK
      response, as disruption of the targeting of PKA with the peptide HT31 resulted in
      marked changes in the CCK-evoked [Ca(2+)](c) signal but had no effect on ACh
      evoked responses. Stimulation of cells with bombesin, which evokes [Ca(2+)](c)
      oscillations indistinguishable from those produced by CCK, also results in PKA
      mediated phosphorylation of type III InsP(3)R. Thus, we conclude that PKA
      mediated phosphorylation of type III InsP(3)R is a general mechanism by which the
      patterns of [Ca(2+)](c) oscillations are shaped in pancreatic acinar cells.

PMID- 12065598
TI  - The human acid alpha-glucosidase gene is a novel target of the Notch-1/Hes-1
      signaling pathway.
AB  - Acid alpha-glucosidase (GAA) is a lysosomal enzyme that degrades glycogen. A
      deficiency of GAA is responsible for a recessively inherited myopathy and
      cardiomyopathy, glycogenosis type II. Previously, we identified an intronic
      repressor element in the GAA gene and demonstrated that Hes-1, a basic helix-loop
      helix factor, binds to a C class E box within the element and functions as a
      transcriptional repressor in HepG2 cells. Hes-1 is a well studied downstream
      target gene in the Notch signaling pathway. In this study, over-expression and
      depletion of Notch-1 intracellular domain (NICD) strategies were used to
      investigate whether expression of the GAA gene is under the control of Notch
      1/Hes-1 signaling. In co-transfection experiments, Hes-1, up-regulated by over
      expressed NICD, enhanced the repressive effect of the DNA element with wild type
      Hes-1 binding sites but not with mutant Hes-1 binding sites. Conversely,
      depletion of Notch-1 with phosphorothioated antisense oligonucleotides,
      corresponding to the fourth ankyrin repeat within NICD, led to reduced Hes-1.
      Constitutively over-expressed Hes-1 and Notch-1 repressed GAA gene expression.
      Therefore, our data establish that the human GAA gene, encoding a lysosomal
      enzyme, is a downstream target of the Notch-1/Hes-1 signaling pathway.

PMID- 12065599
TI  - Cis elements of the villin gene control expression in restricted domains of the
      vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine.
AB  - Villin, an actin bundling protein found in the apical brush border of absorptive
      tissues, is one of the first structural genes to be transcriptionally activated
      in the embryonic intestinal endoderm. In the adult, villin is broadly expressed
      in every cell of the intestinal epithelium on both the vertical axis (crypt to
      villus tip) and the horizontal axis (duodenum through colon) of the intestine.
      Here, we document that a 12.4-kilobase region of the mouse villin gene drives
      high level expression of two different reporter genes (LacZ and Cre recombinase)
      within the entire intestinal epithelium of transgenic mice. Deletion of a portion
      of this transgene results in reduction of beta-galactosidase activity in
      restricted domains of the small intestine (duodenum) and large intestine (cecum).
      In addition, expression is reduced in the crypt compartment throughout the
      intestine. Thus, the global expression pattern of villin in the intestine is
      apparently the consequence of an amalgam of distinct and individual domain
      specific control processes. That is, expression of villin in the duodenum and
      cecum requires different regulatory sequences than the rest of the intestine, and
      the expression of villin in crypts is regulated by different circuitry than
      expression of villin on villus tips.

PMID- 12065600
TI  - The stimulation of glycolysis by hypoxia in activated monocytes is mediated by
      AMP-activated protein kinase and inducible 6-phosphofructo-2-kinase.
AB  - The activation of monocytes involves a stimulation of glycolysis, release of
      potent inflammatory mediators, and alterations in gene expression. All of these
      processes are known to be further increased under hypoxic conditions. The
      activated monocytes express inducible 6-phosphofructo-2-kinase (iPFK-2), which
      synthesizes fructose 2,6-bisphosphate, a stimulator of glycolysis. During
      ischemia, AMP-activated protein kinase (AMPK) activates the homologous heart 6
      phosphofructo-2-kinase isoform by phosphorylating its Ser-466. Here, we studied
      the involvement of AMPK and iPFK-2 in the stimulation of glycolysis in activated
      monocytes under hypoxia. iPFK-2 was phosphorylated on the homologous serine (Ser
      461) and activated by AMPK in vitro. The activation of human monocytes by
      lipopolysaccharide induced iPFK-2 expression and increased fructose 2,6
      bisphosphate content and glycolysis. The incubation of activated monocytes with
      oligomycin, an inhibitor of oxidative phosphorylation, or under hypoxic
      conditions activated AMPK and further increased iPFK-2 activity, fructose 2,6
      bisphosphate content, and glycolysis. In cultured human embryonic kidney 293
      cells, the expression of a dominant-negative AMPK prevented both the activation
      and phosphorylation of co-transfected iPFK-2 by oligomycin. It is concluded that
      the stimulation of glycolysis by hypoxia in activated monocytes requires the
      phosphorylation and activation of iPFK-2 by AMPK.

PMID- 12065601
TI  - Regulation of calreticulin expression during induction of differentiation in
      human myeloid cells. Evidence for remodeling of the endoplasmic reticulum.
AB  - Induction of differentiation of HL-60 human myeloid cells profoundly affected
      expression of calreticulin, a Ca(2+)-binding endoplasmic reticulum chaperone.
      Induction with Me(2)SO or retinoic acid reduced levels of calreticulin protein by
      approximately 60% within 4 days. Pulse-chase studies indicated that labeled
      calreticulin decayed at similar rates in differentiated and undifferentiated
      cells (t(12) approximately 4.6 days), but the biosynthetic rate was <10% of
      control after 4 days. Differentiation also induced a rapid decline in
      calreticulin mRNA levels (90% reduction after 1 day) without a decrease in
      transcript stability (t(12) approximately 5 h). Nuclear run-on analysis
      demonstrated rapid down-regulation of gene transcription (21% of control at 2 h).
      Differentiation also greatly reduced the Ca(2+) content of the cells (25% of
      control), although residual Ca(2+) pools remained sensitive to thapsigargin,
      ionomycin, and inositol trisphosphate. Progressive decreases were also observed
      in levels of calnexin and ERp57, whereas BiP/GRP78 and protein disulfide
      isomerase were only modestly affected. Ultrastructural studies showed a
      substantial reduction in endoplasmic reticulum content of the cells. Thus,
      terminal differentiation of myeloid cells was associated with decreased
      endoplasmic reticulum content, selective reductions in molecular chaperones, and
      diminished intracellular Ca(2+) stores, perhaps reflecting an endoplasmic
      reticulum remodeling program as a prominent feature of granulocytic
      differentiation.

PMID- 12065602
TI  - ProSAP/Shank proteins - a family of higher order organizing molecules of the
      postsynaptic density with an emerging role in human neurological disease.
AB  - The postsynaptic density (PSD) is a specialized electron-dense structure
      underneath the postsynaptic plasmamembrane of excitatory synapses. It is thought
      to anchor and cluster glutamate receptors exactly opposite to the presynaptic
      neurotransmitter release site. Various efforts to study the molecular structure
      of the PSD identified several new proteins including membrane receptors, cell
      adhesion molecules, components of signalling cascades, cytoskeletal elements and
      adaptor proteins with scaffolding functions to interconnect these PSD components.
      The characterization of a novel adaptor protein family, the ProSAPs or Shanks,
      sheds new light on the basic structural organization of the PSD. ProSAPs/Shanks
      are multidomain proteins that interact directly or indirectly with receptors of
      the postsynaptic membrane including NMDA-type and metabotropic glutamate
      receptors, and the actin-based cytoskeleton. These interactions suggest that
      ProSAP/Shanks may be important scaffolding molecules of the PSD with a crucial
      role in the assembly of the PSD during synaptogenesis, in synaptic plasticity and
      in the regulation of dendritic spine morphology. Moreover the analysis of a
      patient with 22q13.3 distal deletion syndrome revealed a balanced translocation
      with a breakpoint in the human ProSAP2/Shank3 gene. This ProSAP2/Shank3
      haploinsufficiency may cause a syndrome that is characterized by severe
      expressive language delay, mild mental retardation and minor facial dysmorphisms.

PMID- 12065603
TI  - A perforated patch-clamp study of calcium currents and exocytosis in chromaffin
      cells of wild-type and alpha(1A) knockout mice.
AB  - Simultaneous recordings of inward whole-cell Ca(2+) channel currents (I(Ca) ) and
      increments of capacitance as an indication of exocytosis (Delta(Cm)), were
      performed in voltage-clamped single adrenal chromaffin cells from wild-type and
      alpha(1A) subunit deficient mice, using the perforated-patch configuration of the
      patch-clamp technique. Using protocol #1 (one single Ca(2+) channel blocker per
      cell), to dissect the components of I(Ca), L channels contributed 43%, N channels
      35% and P/Q channels 30% to the total I(Ca) of wild-type cells. Using protocol #2
      (cumulative sequential addition of 3 microm nifedipine, 1 microm omega-conotoxin
      GVIA, and 1 microm omega-agatoxin IVA), L, N and P/Q channels contributed 40%,
      34% and 14%, respectively, to I(Ca); an R component of around 11% remained. In
      wild-type mice the changes of Delta(Cm) paralleled those of I(Ca). In alpha(1A)
      deficient mice the L component of I(Ca) rose to 53% while the P/Q disappeared;
      the N and R components were similar. In these mice, Delta(Cm) associated to N and
      R channels did not vary; however, the P/Q component was abolished while the L
      component increased by 20%. In conclusion, exocytosis was proportional to the
      relative density of each Ca(2+) channel subtype, L, N, P/Q, R. Ablation of the
      alpha(1A) gene led to a loss of P/Q channel current and to a compensatory
      increase of L channel-associated secretion; however, this compensation was not
      sufficient to maintain the overall exocytotic response, that was diminished by
      35% in alpha(1A) -deficient mice. This may be due to altered Ca(2+) homeostasis
      in these mice, as compared to wild mouse chromaffin cells.

PMID- 12065604
TI  - Characterization of a cysteine proteinase inhibitor induced during neuronal cell
      differentiation.
AB  - A rat homolog of human cystatin E/M was identified by differential display of
      transcripts induced during neuronal cell differentiation. A member of the family
      2 cystatins, rat cystatin E/M is secreted, glycosylated and developmentally
      regulated. Rat cystatin E/M is expressed in brain, and is induced during
      differentiation of a conditionally immortalized E17 rat hippocampal cell line
      (H19-7) by bFGF or activated Raf via MEK-dependent and -independent signaling
      pathways. Rat cystatin E/M protein is increased post-transcriptionally in PC12
      cells, and the protein is secreted into the medium of primary embryonal
      hippocampal cultures. Analysis of the K (i) of recombinant His-tagged rat
      cystatin E/M toward cathepsins B and H revealed that rat cystatin E/M has an
      inhibitor profile distinct from that of other members of the cystatin family.
      Motif swapping between rat cystatin E/M and human cystatin C, a well
      characterized cystatin, identified some residues that can contribute to the
      specificity of inhibition. Taken together, these results describe a member of the
      cystatin family that has a distinct inhibitor profile and may play a role in
      neuronal development.

PMID- 12065605
TI  - Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP
      synthesis and characterization by [(3) H]tiotidine binding.
AB  - In this study, histamine (HA) receptors in chick cerebral cortex were
      characterized using two approaches: (1) analysis of the effects of HA-ergic drugs
      on the cAMP-generating system, and (2) radioreceptor binding of [(3) H]tiotidine,
      a selective H(2) antagonist. HA was a weak activator of adenylyl cyclase in a
      crude membrane preparation of chick cerebrum. On the other hand, HA (0.1-1000
      microm) potently and concentration dependently stimulated cAMP production in [(3)
      H]adenine pre-labelled slices of chick cerebral cortex, displaying an EC(50)
      value (concentration that produces 50% of maximum response) of 2.65 microm. The
      effect of HA was mimicked by agonists of HA receptors with the following rank
      order of potency: HA >or= 4-methylHA (H(2)) >or= N alpha,N alpha-dimethylHA (H(3)
      >> H(2) = H(1)) >> 2-methylHA (H(1)) >> 2-thiazolylethylamine (H(1)) >or= R alpha
      methylHA (H(3)) >> amthamine, dimaprit (H(2)), immepip (H(3), H(4)). The HA
      evoked increase in cAMP production in chick cerebral cortex was antagonized by
      selective H(2) receptor blockers (aminopotentidine >or= tiotidine > ranitidine >>
      zolantidine), and not significantly affected by mepyramine and thioperamide,
      selective H(1) and H(3) /H(4) receptor blockers, respectively. A detailed
      analysis of the antagonistic action of aminopotentidine (vs. HA) revealed a non
      competitive mode of action. The binding of [(3) H]tiotidine to chick cortical
      membranes was rapid, stable and reversible. Saturation analysis resulted in a
      linear Scatchard plot, suggesting binding to a single class of receptor binding
      site with high affinity [equilibrium dissociation constant (K (d)) = 4.42 nm] and
      high capacity [maximum number of binding sites (B (max) ) = 362 fmol/mg protein].
      The relative rank order of HA-ergic drugs to inhibit [(3) H]tiotidine binding to
      chick cerebrum was: antagonists - tiotidine >> aminopotentidine = ranitidine >or=
      zolantadine >> thioperamide - triprolidine; agonists - HA >or= 4-methylHA >> 2
      methylHA >or=R alpha-methylHA - dimaprit. In conclusion, chick cerebral cortex
      contains H(2) -like HA receptors that are linked to the cAMP-generating system
      and are labelled with [(3) H]tiotidine. The pharmacological profile of these
      receptors is different from that described for their mammalian counterpart. It is
      suggested that the studied receptors represent either an avian-specific H(2) 
      like HA receptors or a novel subtype of HA receptors.

PMID- 12065606
TI  - Species differences in the expression of multiple tyrosine hydroxylase protein
      isoforms.
AB  - In subprimates, a single form of tyrosine hydroxylase (TH) is expressed, whereas
      two TH protein isoforms have been identified in monkeys and four isoforms have
      been demonstrated in humans. In order to establish the evolutionary
      pattern/emergence of these multiple TH isoforms, adrenal medullae from different
      mammalian species were analyzed by blot immunolabeling using pan-specific TH
      antibodies and antibodies specific to each of the four human TH isoforms. The
      expression of multiple TH isoforms was primate specific and restricted to
      anthropoids: only a single TH isoform was detected in adrenal medullae from
      several subprimate and prosimian species (six species from four families), while
      two TH isoforms were found in all of the anthropoid species studied. The presence
      of four TH isoforms could only be demonstrated in human specimens. Contrary to
      previous suggestions, only one TH protein isoform was found in rats and only four
      TH protein isoforms were found in humans.

PMID- 12065607
TI  - Increased brain histamine levels in Parkinson's disease but not in multiple
      system atrophy.
AB  - We investigated histamine concentration in post-mortem brain samples of patients
      with Parkinson's disease (PD, n = 24), multiple system atrophy (MSA, n = 8) and
      age-matched controls (n = 27). Histamine concentrations were significantly
      increased in the putamen (to 159% of the control mean), substantia nigra pars
      compacta (to 201%), internal globus pallidus (to 234%) and external globus
      pallidus (to 200%), i.e. in areas which play a crucial role in the motor
      behaviour and which show typical functional alterations in PD. In MSA no
      significant differences were seen. Tele-methylhistamine (histamine metabolite)
      concentrations were unchanged in PD. These results indicate that histamine
      concentration, but not its metabolism is increased in PD, but not in MSA. This
      finding may have implications in developing new drug therapies for PD and in
      differential diagnosis between PD and MSA.

PMID- 12065608
TI  - Studies, using in vivo microdialysis, on the effect of the dopamine uptake
      inhibitor GBR 12909 on 3,4-methylenedioxymethamphetamine ('ecstasy')-induced
      dopamine release and free radical formation in the mouse striatum.
AB  - The present study examined the mechanisms by which 3,4
      methylenedioxymethamphetamine (MDMA) produces long-term neurotoxicity of striatal
      dopamine neurones in mice and the protective action of the dopamine uptake
      inhibitor GBR 12909. MDMA (30 mg/kg, i.p.), given three times at 3-h intervals,
      produced a rapid increase in striatal dopamine release measured by in vivo
      microdialysis (maximum increase to 380 +/- 64% of baseline). This increase was
      enhanced to 576 +/- 109% of baseline by GBR 12909 (10 mg/kg, i.p.) administered
      30 min before each dose of MDMA, supporting the contention that MDMA enters the
      terminal by diffusion and not via the dopamine uptake site. This, in addition to
      the fact that perfusion of the probe with a low Ca(2+) medium inhibited the MDMA
      induced increase in extracellular dopamine, indicates that the neurotransmitter
      may be released by a Ca(2+) -dependent mechanism not related to the dopamine
      transporter. MDMA (30 mg/kg x 3) increased the formation of 2,3-dihydroxybenzoic
      acid (2,3-DHBA) from salicylic acid perfused through a probe implanted in the
      striatum, indicating that MDMA increased free radical formation. GBR 12909 pre
      treatment attenuated the MDMA-induced increase in 2,3-DHBA formation by
      approximately 50%, but had no significant intrinsic radical trapping activity.
      MDMA administration increased lipid peroxidation in striatal synaptosomes, an
      effect reduced by approximately 60% by GBR 12909 pre-treatment. GBR 12909 did not
      modify the MDMA-induced changes in body temperature. These data suggest that MDMA
      induced toxicity of dopamine neurones in mice results from free radical formation
      which in turn induces an oxidative stress process. The data also indicate that
      the free radical formation is probably not associated with the MDMA-induced
      dopamine release and that MDMA does not induce dopamine release via an action at
      the dopamine transporter.

PMID- 12065609
TI  - Metabotropic glutamate receptor 5 and calcium signaling in retinal amacrine
      cells.
AB  - To begin to understand the modulatory role of glutamate in the inner retina, we
      examined the mechanisms underlying metabotropic glutamate receptor 5 (mGluR5)
      dependent Ca(2+) elevations in cultured GABAergic amacrine cells. A partial
      sequence of chicken retinal mGluR5 encompassing intracellular loops 2 and 3
      suggests that it can couple to both G(q) and G(s). Selective activation of mGluR5
      stimulated Ca(2+) elevations that varied in waveform from cell to cell.
      Experiments using high external K(+) revealed that the mGluR5-dependent Ca(2+)
      elevations are distinctive in amplitude and time course from those engendered by
      depolarization. Experiments with a Ca(2+) -free external solution demonstrated
      that the variability in the time course of mGluR5-dependent Ca(2+) elevations is
      largely due to the influx of extracellular Ca(2+). The sensitivity of the initial
      phase of the Ca(2+) elevation to thapsigargin indicates that this phase of the
      response is due to the release of Ca(2+) from the endoplasmic reticulum.
      Pharmacological evidence indicates that mGluR5-mediated Ca(2+) elevations are
      dependent upon the activation of phospholipase C. We rule out a role for L-type
      Ca(2+) channels and cAMP-gated channels as pathways for Ca(2+) entry, but provide
      evidence of transient receptor potential (TRP) channel-like immunoreactivity,
      suggesting that Ca(2+) influx may occur through TRP channels. These results
      indicate that GABAergic amacrine cells express an avian version of mGluR5 that is
      linked to phospholipase C-dependent Ca(2+) release and Ca(2+) influx, possibly
      through TRP channels.

PMID- 12065610
TI  - D(1) dopamine receptor stimulation increases GluR1 phosphorylation in postnatal
      nucleus accumbens cultures.
AB  - Postsynaptic interactions between dopamine and glutamate receptors in the nucleus
      accumbens are critical for acute responses to drugs of abuse and for
      neuroadaptations resulting from their chronic administration. We tested the
      hypothesis that D(1) dopamine receptor stimulation increases phosphorylation of
      the AMPA receptor subunit GluR1 at the protein kinase A phosphorylation site
      (Ser845). Nucleus accumbens cell cultures were prepared from postnatal day 1
      rats. After 14 days in culture, GluR1 phosphorylation was measured by western
      blotting using phosphorylation site-specific antibodies. The D(1) receptor
      agonist SKF 81297 increased Ser845 phosphorylation in a concentration- dependent
      manner, with marked increases occurring within 5 min. This was prevented by the
      D(1) receptor antagonist SCH 23390 and the protein kinase A inhibitor H89, and
      reproduced by forskolin. The D(2) receptor agonist quinpirole attenuated the
      response to D(1) receptor stimulation. Neither D(1) nor D(2) receptor agonists
      altered GluR1 phosphorylation at Ser831, the site phosphorylated by protein
      kinase C and calcium/calmodulin-dependent protein kinase II. In other systems,
      phosphorylation of GluR1 at Ser845 is associated with enhancement of AMPA
      receptor currents. Thus, the present results suggest that AMPA receptor
      transmission in the nucleus accumbens may be augmented by concurrent D(1)
      receptor stimulation.

PMID- 12065611
TI  - Detergent-insoluble glycosphingolipid/cholesterol microdomains of the myelin
      membrane.
AB  - Glycosphingolipids and cholesterol form lateral assemblies, or lipid 'rafts',
      within biological membranes. Lipid rafts are routinely studied biochemically as
      low-density, detergent-insoluble complexes (in non-ionic detergents at 4 degrees
      C; DIGs, detergent-insoluble glycosphingolipid/cholesterol microdomains). Recent
      discrepancies recommended a re-evaluation of the conditions used for the
      biochemical analysis of lipid rafts. We have investigated the detergent
      insolubility of several known proteins present in the
      glycosphingolipid/cholesterol-rich myelin membrane, using four detergents
      representing different chemical classes (TX-100, CHAPS, Brij 96 and TX-102),
      under four conditions: detergent extraction of myelin either at (i) 4 degrees C
      or (ii) 37 degrees C, or at 4 degrees C after pre-extraction with (iii) saponin
      or (iv) methyl-beta-cyclodextrin (MbetaCD). Each detergent was different in its
      ability to solubilize myelin proteins and in the density of the DIGs produced.
      Brij 96 DIGs floated to a lower density than other detergents tested, possibly
      representing a subpopulation of DIGs in myelin. DIGs pre-extracted with saponin
      were denser than DIGs pre-extracted with MbetaCD. Furthermore, pre-extraction
      with MbetaCD solubilized proteolipid protein (known to associate with
      cholesterol), whereas pre-extraction with saponin did not, suggesting that
      saponin is less effective as a cholesterol-perturbing agent than is MbetaCD.
      These results demonstrate that DIGs isolated by different detergents are not
      necessarily comparable, and that these detergent-specific DIGs may represent
      distinct biochemical, and possibly physiological, entities based on the
      solubilities of specific lipids/proteins in each type of detergent.

PMID- 12065612
TI  - Age-related loss of extrastriatal dopamine D(2) -like receptors in women.
AB  - Positron emission tomography (PET) studies have indicated that the in vivo
      availability of dopamine D(2) -like receptors declines with age in the human
      brain. Most of the studies have been carried out with healthy male subjects, or
      with subject groups containing both sexes. The authors have recently demonstrated
      that the availability of D(2) -like receptors in the frontal cortex is higher in
      women than in men. The present study was aimed to further examine this
      phenomenon. Thirty-seven healthy women (age range 22-78 years) were examined with
      PET and [(11) C]FLB 457, a high-affinity tracer for the extrastriatal D(2) -like
      receptors. A negative relationship between age and dopamine D(2) -like receptor
      availability was seen in the frontal cortex (decrease of 12% per decade of life),
      the temporal cortex (9%) and the thalamus (6%). A non-linear s-shape association
      explained the relationship only in the frontal cortex, while in other regions the
      association was linear. Neither oestradiol nor progesterone levels had a
      significant relationship with the [(11) C]FLB 457 uptake in any of the brain
      regions studied after the effect of age was partialled out. The results indicate
      that: (i) the extrastriatal D(2) -like receptor availability decreases with age
      in healthy women with the fastest rate in the frontal cortex and with the overall
      rate close to the rate reported in healthy men; (ii) around midlife (age 40-60
      years) in women, the frontal receptor decline plateaus while the decline
      continues to be linear in other extrastriatal brain regions; and (iii) serum
      oestradiol or progesterone levels are not associated with cortical or thalamic
      D(2) -like receptor availability in women. The results may prove to be important
      in studies where the biochemical basis of clinical sex differences is examined in
      patients with dopamine-related neuropsychiatric disorders.

PMID- 12065613
TI  - A non-amyloidogenic function of BACE-2 in the secretory pathway.
AB  - beta-Site amyloid precursor protein cleavage enzyme (BACE)-1 and BACE-2 are
      members of a novel family of membrane-bound aspartyl proteases. While BACE-1 is
      known to cleave beta-amyloid precursor protein (betaAPP) at the beta-secretase
      site and to be required for the generation of amyloid beta-peptide (Abeta), the
      role of its homologue BACE-2 in amyloidogenesis is less clear. We now demonstrate
      that BACE-1 and BACE-2 have distinct specificities in cleavage of betaAPP in
      cultured cells. Radiosequencing of the membrane-bound C-terminal cleavage product
      revealed that BACE-2 cleaves betaAPP in the middle of the Abeta domain between
      phenylalanines 19 and 20, resulting in increased secretion of APPs-alpha- and p3
      like products and reduced production of Abeta species. This cleavage can occur in
      the Golgi and later secretory compartments. We also demonstrate that BACE-1
      mediated cleavage of betaAPP at Asp1 of the Abeta domain can occur as early as in
      the endoplasmic reticulum, while cleavage at Glu11 occurs in later compartments.
      These data indicate that the distinct specificities of BACE-1 and BACE-2 in their
      cleavage of betaAPP differentially affect the generation of Abeta.

PMID- 12065614
TI  - Cocaine treatment increases extracellular cholecystokinin (CCK) in the nucleus
      accumbens shell of awake, freely moving rats, an effect that is enhanced in rats
      that are behaviorally sensitized to cocaine.
AB  - Cholecystokinin (CCK) is co-localized with dopamine, is known to modulate
      dopamine neurotransmission and is involved in behavioral sensitization to
      psychostimulants. To better understand its role, CCK was measured by
      microdialysis in the nucleus accumbens (NAC) shell in response to cocaine in drug
      naive rats and in rats that are behaviorally sensitized to cocaine. Basal
      extracellular levels of CCK in drug-naive rats were 0.17 pg/20 min fraction,
      while in cocaine-sensitized rats, they were significantly higher (0.56 pg).
      Treating drug-naive rats with cocaine caused a significant increase in CCK to
      0.58 pg. Cocaine treatment of cocaine-sensitized rats increased CCK to 0.98. When
      analyzed as a function of time after cocaine treatment, these increases were
      sustained and were significantly different from CCK levels of saline-treated
      rats. In cocaine-sensitized rats, CCK levels following cocaine treatment were
      also significantly higher than levels in drug-naive animals receiving a single
      injection of cocaine. These results provide evidence for an activation of the
      mesolimbic and/or cerebral cortical CCK system in response to repeated cocaine
      administration. These results provide a neurochemical basis for an important role
      of CCK (via modulation of dopamine neurotransmission) in expression of cocaine
      sensitization.

PMID- 12065615
TI  - In vivo activation of N-methyl-D-aspartate receptors in the rat hippocampus
      increases prostaglandin E(2) extracellular levels and triggers lipid peroxidation
      through cyclooxygenase-mediated mechanisms.
AB  - Cyclooxygenases (COX) are a family of enzymes involved in the biosynthesis of
      prostaglandin (PG) and thromboxanes. The inducible enzyme cyclooxygenase-2 (COX
      2) is the major isoform found in normal brain, where it is constitutively
      expressed in neurons and is further up-regulated during several pathological
      events, including seizures and ischaemia. Emerging evidence suggests that COX-2
      is implicated in excitotoxic neurodegenerative phenomena. It remains unclear
      whether PGs or other products associated to COX activity take part in these
      processes. Indeed, it has been suggested that reactive oxygen species, produced
      by COX, could mediate neuronal damage. In order to obtain direct evidence of free
      radical production during COX activity, we undertook an in vivo microdialysis
      study to monitor the levels of PGE(2) and 8-epi-PGF(2alpha) following infusion of
      N-methyl-D-aspartate (NMDA). A 20-min application of 1 mm NMDA caused an
      immediate, MK-801-sensitive increase of both PGE(2) and 8-epi-PGF(2alpha) basal
      levels. These effects were largely prevented by the specific cytosolic
      phospholipase A(2) (cPLA(2) ) inhibitor arachidonyl trifluoromethyl ketone (ATK),
      by non- selective COX inhibitors indomethacin and flurbiprofen or by the COX-2
      selective inhibitor NS-398, suggesting that the NMDA-evoked prostaglandin
      synthesis and free radical-mediated lipid peroxidation are largely dependent on
      COX-2 activity. As several lines of evidence suggest that prostaglandins may be
      potentially neuroprotective, our findings support the hypothesis that free
      radicals, rather than prostaglandins, mediate the toxicity associated to COX-2
      activity.

PMID- 12065616
TI  - D(3) receptor ligands modulate extracellular dopamine clearance in the nucleus
      accumbens.
AB  - An involvement of the D(3) dopamine receptor in the regulation of extracellular
      dopamine has been suggested. However, the mechanisms mediating this effect are
      unclear. We have used the technique of no net flux microdialysis under transient
      conditions to examine the influence of the D(3) -preferring agonist (+)-PD128907
      upon extracellular dopamine levels in the nucleus accumbens of the mouse. (+)-PD
      128907 (0.1 mg/kg intraperitoneally) significantly decreased extracellular
      dopamine. This decrease was associated with a marked increase in the extraction
      fraction, which suggests an increase in dopamine clearance. The ability of D(3) 
      preferring compounds to modulate dopamine uptake was investigated in vitro using
      rotating disk electrode voltammetry. (+)-PD 128907 (10 nm) significantly
      increased the initial clearance rate of 3 microm dopamine in rat nucleus
      accumbens tissue suspensions. Kinetic analysis revealed no change in the apparent
      K (m) of uptake but it showed a 33% increase in V (max). In contrast, the D(3)
      antagonist GR 103691 (10 nm) significantly decreased dopamine uptake. Consistent
      with the low levels of D(3) receptors in the dorsal striatum, neither compound
      affected uptake in tissue suspensions from this brain region. These data indicate
      that D(3) receptor activation increases dopamine uptake in the nucleus accumbens
      and suggest that this receptor subtype can regulate extracellular dopamine by
      modulating the DA transporter activity.

PMID- 12065617
TI  - Divergent pathways account for two distinct effects of amyloid beta peptides on
      exocytosis and Ca(2+) currents: involvement of ROS and NF-kappaB.
AB  - Amyloid peptides (AbetaPs) are implicated in neuronal death associated with
      Alzheimer's disease. Their toxicity involves disruption cellular Ca(2+)
      homeostasis, leading to activation of caspases and cell death. Antioxidants can
      prevent such cell death and show beneficial clinical effects in Alzheimer's
      disease patients. Using the model neurosecretory cell line, PC12, we have shown
      that AbetaPs cause enhancement of evoked exocytosis via formation of a Cd(2+) 
      resistant Ca(2+) influx pathway, and also cause selective, functional up
      regulation of current through L-type Ca(2+) channels. The involvement of reactive
      oxygen species (ROS) in these effects were investigated by examining the ability
      of various antioxidants to interfere with these responses. Both melatonin and
      ascorbic acid fully blocked the enhancement of catecholamine secretion caused by
      application of AbetaP((1-40)), as monitored in real time amperometrically, but
      inhibition of the transcriptional regulator NF-kappaB with SN-50 did not affect
      secretion. Enhanced immunofluorescence, observed in AbetaP-treated cells using a
      monoclonal antibody raised against the N-terminus of AbetaP, was also suppressed
      by melatonin. Ascorbic acid, melatonin and ebselen also fully prevented
      augmentation of whole-cell Ca(2+) currents caused by application of AbetaP((1
      40)). By contrast, inhibitors of NF-kappaB (sulfasalazine and SN-50) were able to
      prevent AbetaP induced Ca(2+) channel current enhancement, whilst inhibitors of
      mitogen-activated protein kinase and protein kinase C could not. Our results
      indicate that augmentation or induction by AbetaPs of two important, distinct
      factors regulating Ca(2+) homeostasis is mediated by increased ROS production,
      but only one of these (up-regulation of native Ca(2+) channels) requires
      activation of NF-kappaB.

PMID- 12065619
TI  - Transglutaminase overexpression sensitizes neuronal cell lines to apoptosis by
      increasing mitochondrial membrane potential and cellular oxidative stress.
AB  - 'Tissue' transglutaminase (tTG) selectively accumulates in cells undergoing
      apoptosis both in vivo and in vitro. Considering the central role played by
      mitochondria in apoptosis, we investigated the relationships existing amongst tTG
      expression, apoptosis and mitochondrial function. To this aim we studied the
      mechanisms of apoptosis in a neuronal cell line (SK-N-BE (2)) in which the tTG
      expression was driven by a constitutive promoter. Furthermore, a tet-off
      inducible promoter was also used in 3T3 fibroblastic cells used as control. Both
      cell lines, when expressing tTG, appeared 'sensitized' to apoptosis. Strikingly,
      we found major differences in the morphological features of mitochondria among
      cell lines in the absence of apoptotic stimuli. In addition, these
      ultrastructural characteristics were associated with specific functional
      features: (i) constitutively hyperpolarized mitochondria and (ii) increased
      reactive oxygen intermediates production. Importantly, after mitochondrial
      mediated apoptosis by staurosporine, a rapid loss of mitochondrial membrane
      potential was found in tTG cells only. Taken together, these results seem to
      suggest that, via hyperpolarization, tTG might act as a 'sensitizer' towards
      apoptotic stimuli specifically targeted to mitochondria. These results could also
      be of pathogenetic relevance for those diseases that are characterized by
      increased tTG and apoptotic rate together with impaired mitochondrial function,
      e.g. in some neurodegenerative disease.

PMID- 12065618
TI  - Induction of apoptosis in human and rat glioma by agonists of the nuclear
      receptor PPARgamma.
AB  - Malignant astrocytomas are among the most common brain tumours and few
      therapeutic options exist. It has recently been recognized that the ligand
      activated nuclear receptor PPARgamma can regulate cellular proliferation and
      induce apoptosis in different malignant cells. We report the effect of three
      structurally different PPARgamma agonists inducing apoptosis in human (U87MG and
      A172) and rat (C6) glioma cells. The PPARgamma agonists ciglitazone, LY171 833
      and prostaglandin-J2, but not the PPARalpha agonist WY14643, inhibited
      proliferation and induced cell death. PPARgamma agonist-induced cell death was
      characterized by DNA fragmentation and nuclear condensation, as well as inhibited
      by the synthetic receptor-antagonist bisphenol A diglycidyl ether (BADGE). In
      contrast, primary murine astrocytes were not affected by PPARgamma agonist
      treatment. The apoptotic death in the glioma cell lines treated with PPARgamma
      agonists was correlated with the transient up-regulation of Bax and Bad protein
      levels. Furthermore, inhibition of Bax expression by specific antisense
      oligonucleotides protected glioma cells against PPARgamma-mediated apoptosis,
      indicating an essential role of Bax in PPARgamma-induced apoptosis. However,
      PPARgamma agonists not only induced apoptosis but also caused redifferentiation
      as indicated by outgrowth of long processes and expression of the
      redifferentiation marker N-cadherin in response to PPARgamma agonists. Taken
      together, treatment of glioma cells with PPARgamma agonists may hold therapeutic
      potential for the treatment of gliomas.

PMID- 12065620
TI  - Alternative splicing isoform of tau protein kinase I/glycogen synthase kinase
      3beta.
AB  - Glycogen synthase kinase 3 (GSK3) plays important roles in Wnt and insulin
      signaling, cell fate determination, and Alzheimer-like tau phosphorylation. We
      discovered an isoform of tau protein kinase I (TPKI)/GSK3beta with a 13 amino
      acid insert in the catalytic domain owing to alternative splicing. The
      alternative transcripts were found in the brains of the mouse, rat and human,
      with highly conserved sequences. The variant protein, named TPKI2/GSK3beta2, was
      abundant in the brain. Immunohistochemistry indicated differential distribution
      of the conventional and the new TPKI/GSK3beta isoforms within young neurons.
      TPKI2/GSK3beta2 showed decreased kinase activities towards two phosphorylation
      sites on tau compared with the conventional isoform. Immunohistochemistry
      indicated that TPKI2/GSK3beta2 occurs predominantly in the neuronal soma, while
      TPKI1/GSK3beta1 is found both in the soma and processes. These results indicate
      that the new splice isoform has a different function. Because the amino acid
      insert occurs in the domain implicated in interaction with a protein phosphatase
      in a homologous kinase cdk-2, the alternative splicing can regulate multiprotein
      complex formation and function involving TPKI/GSK3beta.

PMID- 12065622
TI  - Heterogeneity of normal prion protein in two- dimensional immunoblot: presence of
      various glycosylated and truncated forms.
AB  - The common use of one-dimensional (1-D) immunoblot with a single monoclonal
      antibody (Mab) engenders the notion that the normal or cellular prion protein
      (PrP(C) ) comprises few and simple forms. In this study we used two-dimensional
      (2-D) immunoblot with a panel Mabs to various regions of the prion protein to
      demonstrate the complexity of the PrP(C) present in human brain. We distinguished
      over 50 immunoblot spots, each representing a distinct PrP(C) species based on
      combinations of different molecular weights and isoelectric points (pIs). The
      PrP(C) heterogeneity is due to the presence of a full-length and two major
      truncated forms as well as to the diversity of the glycans linked to most of
      these forms. The two major truncated forms result from distinct cleavage sites
      located at the N-terminus. In addition, enzymatic removal of sialic acid and
      lectin binding studies indicate that the glycans linked to the full-length and
      truncated PrP(C) forms differ in their structure and ratios of the glycoforms.
      The truncation of PrP(C) and the heterogeneity of the linked glycans may play a
      role in regulating PrP(C) function. Furthermore, the presence of relatively large
      quantities of different PrP(C) species may provide additional mechanisms by which
      the diversity of prion strains could be generated.

PMID- 12065621
TI  - Docosahexaenoic acid provides protection from impairment of learning ability in
      Alzheimer's disease model rats.
AB  - Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been
      implicated in restoration and enhancement of memory-related functions. Because
      Alzheimer's disease impairs memory, and infusion of amyloid-beta (Abeta) peptide
      (1-40) into the rat cerebral ventricle reduces learning ability, we investigated
      the effect of dietary pre-administration of docosahexaenoic acid on avoidance
      learning ability in Abeta peptide-produced Alzheimer's disease model rats. After
      a mini-osmotic pump filled with Abeta peptide or vehicle was implanted in
      docosahexaenoic acid-fed and control rats, they were subjected to an active
      avoidance task in a shuttle avoidance system apparatus. Pre-administration of
      docosahexaenoic acid had a profoundly beneficial effect on the decline in
      avoidance learning ability in the Alzheimer's disease model rats, associated with
      an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid
      molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid
      pre-administration furthermore increased cortico-hippocampal reduced glutathione
      levels and glutathione reductase activity, and suppressed the increase in lipid
      peroxide and reactive oxygen species levels in the cerebral cortex and
      hippocampus of the Alzheimer's disease model rats, suggesting an increase in
      antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means
      for preventing the learning deficiencies of Alzheimer's disease.

PMID- 12065623
TI  - Characterization of [(125) I]epibatidine binding and nicotinic agonist-mediated
      (86) Rb(+) efflux in interpeduncular nucleus and inferior colliculus of beta2
      null mutant mice.
AB  - The beta2 nicotinic acetylcholine receptor subunit null mutation eliminated most
      high affinity [(3) H]epibatidine binding in mouse brain, but significant binding
      remained in accessory olfactory nucleus, medial habenula, inferior colliculus and
      interpeduncular nucleus. Residual [(125) I]epibatidine binding sites in the
      inferior colliculus and interpeduncular nucleus were subsequently characterized.
      Inhibition of [(125) I]epibatidine binding by 12 agonists and six antagonists was
      very similar in these regions. Most acetylcholine-stimulated (86) Rb(+) efflux is
      eliminated in thalamus and superior colliculus of beta2 null mutants, but
      significant activity remained in inferior colliculus and interpeduncular nucleus.
      This residual activity was subsequently characterized. The 12 nicotinic agonists
      tested elicited concentration-dependent (86) Rb(+) efflux. Epibatidine was the
      most potent agonist. Cytisine was also potent and efficacious. EC(50) values for
      quaternary agonists were relatively high. Cytisine-stimulated (86) Rb(+) efflux
      was inhibited by six classical nicotinic antagonists. Mecamylamine and D
      tubocurarine were most potent, while decamethonium was the least potent. Agonists
      and antagonists exhibited similar potency in both brain regions. Alpha
      bungarotoxin (100 nm) did not significantly inhibit cytisine-stimulated (86)
      Rb(+) efflux, while the alpha3beta4 selective antagonist, alphaConotoxinAuIB,
      inhibited a significant fraction of the response in both brain regions. Thus,
      beta2 null mutant mice express residual nicotinic activity with properties
      resembling those of alpha3beta4*-nAChR.

PMID- 12065625
TI  - The metabotropic glutamate receptor mGluR7b binds to the catalytic gamma-subunit
      of protein phosphatase 1.
AB  - Correct targeting of enzymes represents an important biological mechanism to
      control post-translational modifications of neurotransmitter receptors. The
      metabotropic glutamate receptor type 7 (mGluR7) exists in two splice variants
      (mGluR7a and mGluR7b), defined by different C-termini that are phosphorylated by
      protein kinase C (PKC). Recently, the search for mGluR7a binding partners yielded
      several proteins that interacted with its C-terminus. Here, a yeast two-hybrid
      screen using the mGluR7b C-terminus identified both variants of the catalytic
      gamma-subunit of protein phosphatase 1 (PP1gamma1 and PP1gamma2) as binding
      partners. The minimal interacting region of PP1gamma1/2 contained the core domain
      and was homologous to a region of PP1alpha that is needed for functional
      expression. Although this core domain is highly conserved within the protein
      phosphatase family, PP1alpha1 and PP1beta did not interact with mGluR7b. Binding
      between PP1gamma1 and mGluR7b might be regulated by alternative splicing, as the
      variant-specific distal part of the mGluR7b C-terminus mediated the interaction.
      Within this domain, amino acids involved in the binding to PP1gamma1 were mapped
      and biochemical assays using recombinant and native proteins verified the
      proposed interaction. Finally, the expression pattern of PP1gamma1, PP1gamma2 and
      mGluR7b was analysed in various CNS regions. In summary, these results suggest a
      regulation of mGluR7b by PP1gamma.

PMID- 12065624
TI  - Phospholipase C-mediated signalling is not required for histamine-induced
      catecholamine secretion from bovine chromaffin cells.
AB  - A possible role for signalling through phospholipase C in histamine-induced
      catecholamine secretion from bovine adrenal chromaffin cells has been
      investigated. Secretion evoked by histamine over 10 min was not prevented by
      inhibiting inositol-1,4,5-trisphosphate receptors with 2-APB, by blocking
      ryanodine receptors with a combination of ryanodine and caffeine, or by depleting
      intracellular Ca(2+) stores by pretreatment with thapsigargin. Inhibition of
      protein kinase C with Ro31-8220 also failed to reduce secretion. Inhibition of
      phospholipase C with ET-18-OCH(3) reduced both histamine- and K(+) -induced
      inositol phosphate responses by 70-80% without reducing their secretory
      responses. Stimulating phospholipase C with Pasteurella multocida toxin did not
      evoke secretion or enhance the secretory response to histamine. The secretory
      response to histamine was little affected by tetrodotoxin or by substituting
      extracellular Na(+) with N -methyl-d-glucamine(+) or choline(+), or by
      substituting external Cl(-) with nitrate(-). Blocking various K(+) channels with
      apamin, charybdotoxin, Ba(2+), tetraethylammonium, 4-aminopyridine, tertiapin or
      glibenclamide failed to reduce the ability of histamine to evoke secretion. These
      results indicate that histamine evokes secretion by a mechanism that does not
      require inositol-1,4,5-trisphosphate-mediated mobilization of stored Ca(2+),
      diacylglycerol-mediated activation of protein kinase C, or activation of
      phospholipase C. The results are consistent with histamine acting by depolarizing
      chromaffin cells through a phospholipase C-independent mechanism.

PMID- 12065626
TI  - Progressive decrease of amyloid precursor protein carboxy terminal fragments (APP
      CTFs), associated with tau pathology stages, in Alzheimer's disease.
AB  - Amyloid precursor protein (APP) dysfunction is a key aetiologic agent in
      Alzheimer's disease (AD). The processing of this transmembrane protein generates
      carboxy terminal fragments (CTFs) upstream of beta-amyloid peptide (Abeta)
      production. The physiologic significance of APP-CTFs is still poorly understood,
      as well as the relationship that could link APP dysfunction and tau pathology in
      familial and non-familial AD (non-FAD). In the present study, we have
      investigated the quantitative and qualitative changes of APP-CTFs in different
      brain areas of non-demented and demented patients from a prospective and
      multidisciplinary study. A significant decrease of the five APP-CTFs was
      observed, which correlated well with the progression of tau pathology, in most
      cases with infraclinical AD and AD, either familial or non-FAD. Furthermore,
      solubility properties and the ratio between the five bands were also modified,
      both in the Triton-soluble and/or -insoluble fractions. Together, we show here
      for the first time a modification directly observed on APP-CTFs upstream of Abeta
      products and its relationship with tau pathology, which could reflect the basic
      aetiological mechanisms of AD.

PMID- 12065627
TI  - Involvement of NF-Y and Sp1 in basal and cAMP-stimulated transcriptional
      activation of the tryptophan hydroxylase (TPH ) gene in the pineal gland.
AB  - The expression of the tryptophan hydroxylase (TPH) gene, encoding the rate
      limiting enzyme of serotonin biosynthesis, is tightly regulated both at the
      transcriptional and at the post-transcriptional levels. In the pineal gland,
      transcription of the gene is activated in response to an intracellular circadian
      increase of the cAMP concentration. We have previously shown that transcription
      of a 2.1-kb fragment of the human TPH promoter is induced by cAMP, although it
      lacks the canonical cAMP responsive element, CRE. The minimal promoter (-73/+29)
      has only weak transcriptional activity but is responsive to cAMP. It contains an
      inverted CCAAT box, which was demonstrated to be involved in this response. Here,
      we have extended our investigation to the functional features of the inverted
      CCAAT box in the -252/+29 TPH promoter, which has a higher basal activity. We
      show that an additional cis -acting sequence, the adjacent GC-rich region,
      cooperates with the inverted CCAAT box for the full activation of basal
      transcription, and that both elements are essential for the full cAMP response.
      We also show that in pinealocytes, NF-Y and Sp1 transactivators bind the inverted
      CCAAT box and GC-rich-region, respectively. These factors participate in a novel
      pathway for the cAMP-mediated response of the TPH promoter, which is independent
      of the canonical CRE-mediated response.

PMID- 12065628
TI  - Protection against 3,4-methylenedioxymethamphetamine-induced neurodegeneration
      produced by glutathione depletion in rats is mediated by attenuation of
      hyperthermia.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) administration produces neurotoxic
      degeneration of serotonin terminals in rat brain. These effects occur only after
      systemic administration and not after central injection, suggesting that
      peripheral metabolism, possibly hepatic, is required for toxicity. Glutathione is
      one of the principal cellular defence mechanisms, but conjugation with
      glutathione can, on some occasions, increase the reactivity of certain molecules.
      Previous studies have shown that central administration of glutathione adducts of
      a MDMA metabolite produces a neurotoxicity profile similar to that of systemic
      MDMA. In the present study, depletion of peripheral (hepatic) glutathione by 43%
      with dl-buthionine-(S,R)-sulfoximine (an inhibitor of glutathione synthesis) did
      not attenuate MDMA-induced neurotoxicity as indicated by the 34% loss of [(3)
      H]paroxetine binding to the serotonin uptake sites in Dark Agouti rats treated
      with the inhibitor. However, a more profound depletion (92%) of glutathione by
      diethylmaleate (direct conjugation) administration significantly reduced the
      serotonergic neurotoxicity produced by MDMA. This depletion protocol also
      attenuated the hyperthermic response to MDMA. A combination protocol utilising
      both buthionine-(S,R)-sulfoximine and diethylmaleate that did not alter the
      hyperthermic response of the rats given MDMA also failed to attenuate the
      neurotoxicity. These findings indicate that glutathione depletion does not offer
      specific protection against MDMA-induced serotonin neurotoxicity in Dark Agouti
      rats.

PMID- 12065629
TI  - GM1 ganglioside induces phosphorylation and activation of Trk and Erk in brain.
AB  - We investigated the ability of GM1 to induce phosphorylation of the tyrosine
      kinase receptor for neurotrophins, Trk, in rat brain, and activation of possible
      down-stream signaling cascades. GM1 increased phosphorylated Trk (pTrk) in slices
      of striatum, hippocampus and frontal cortex in a concentration- and time
      dependent manner, and enhanced the activity of Trk kinase resulting in receptor
      autophosphorylation. The ability of GM1 to induce pTrk was shared by other
      gangliosides, and was blocked by the selective Trk kinase inhibitors K252a and
      AG879. GM1 induced phosphorylation of TrkA > TrkC > TrkB in a region-specific
      distribution. Adding GM1 to brain slices activated extracellular-regulated
      protein kinases (Erks) in all three brain regions studied. In striatum, GM1
      elicited activation of Erk2 > Erk1 in a time-and concentration-dependent manner.
      The GM1 effect on Erk2 was mimicked by other gangliosides, and was blocked by the
      Trk kinase inhibitors K252a and AG879. Pertussis toxin, as well as Src protein
      tyrosine kinase and protein kinase C inhibitors, did not prevent the GM1-induced
      activation of Erk2, apparently excluding the participation of Gi and Gq/11
      protein-coupled receptors. Intracerebroventricular administration of GM1 induced
      a transient phosphorylation of TrkA and Erk1/2 in the striatum and hippocampus
      complementing the in situ studies. These observations support a role for GM1 in
      modulating Trk and Erk phosphorylation and activity in brain.

PMID- 12065630
TI  - Injury-induced "switch" from GTP-regulated to novel GTP-independent isoform of
      tissue transglutaminase in the rat spinal cord.
AB  - We recently found that alternative transcripts of tissue transglutaminase (tTG or
      TG2) were present in hippocampal brain regions of Alzheimer's disease (AD), but
      not in control, non-demented, age-matched brains. Since antecedent non-severe
      trauma has been implicated in AD and other neurodegenerative diseases, such as
      Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), we were
      interested in whether alternative transcripts might be detected in a model of
      neurotrauma, controlled-contusion spinal cord injury (SCI) in the rat. Implicated
      in diverse roles from growth and differentiation to apoptotic cell death, only
      bifunctional tTG, of the nine member TG family, has dual catalytic activities:
      guanine trinucleotide (GTP) hydrolyzing activity (GTPase), as well as protein
      cross-linking. These functions imply two physiological functions: programmed cell
      life and death. These may have profound roles in the nervous system since studies
      in cultured astrocytes found tTG short (S) mRNA transcripts induced by treatment
      with injury-related cytokines. In the developing rat spinal cord, tTG activity is
      concentrated in ventral horn alpha motoneurons, but neither studies of spinal
      cord tTG gene expression, nor evaluation of the GTP-regulated isoforms in
      tissues, have been reported. We now report increased tTG protein and gene
      expression occurring rapidly after SCI. In parallel, novel appearance of a
      second, short form transcript, in addition to the normal long (L) isoform, occurs
      by 8 h of injury. Up-regulation of tTG message and activity following neural
      injury. with appearance of a truncated GTP-unregulated S form, may represent new
      approaches to drug targets in neurotrauma.

PMID- 12065631
TI  - Desensitization of pigment granule aggregation in Xenopus leavis melanophores:
      melatonin degradation rather than receptor down-regulation is responsible.
AB  - Xenopus laevis melanophores express a high density (B(max) 1224 fmol/mg protein)
      of high-affinity (K(d) 37 pm) cell membrane melatonin receptors. Treatment of
      melanophores with melatonin resulted in a loss of membrane melatonin receptors
      reaching a maximum (approximately 60%) by 6 h. In addition to receptor loss, a
      decline in the potency of melatonin to produce pigment aggregation was observed
      on prolonged treatment. However, the loss of potency (3.8-fold in 24 h and 162
      fold in 96 h) was much slower than loss of receptors, and was completely
      prevented by inclusion of eserine (100 microm), an inhibitor of melatonin
      deacetylation in the culture medium. Incubation of melanophores with [(3)H]
      melatonin showed that eserine prevented metabolism of melatonin to 5
      methoxytryptamine. These results indicate that although receptor density does
      decline on prolonged treatment, this is not responsible for the diminishing
      melatonin potency, which is entirely due to degradation of melatonin by
      deacetylation and subsequent deamination in melanophores.

PMID- 12065632
TI  - Insulin-like growth factor-1 effects on bovine retinal endothelial cell glucose
      transport: role of MAP kinase.
AB  - In order to maintain normal metabolism, the neuroretina is completely dependent
      on the constant delivery of glucose across the retinal microvascular endothelial
      cells comprising the inner blood-retinal barrier. Glucose uptake into these cells
      is influenced by various stimuli, including hypoxia and growth factors. Recently,
      insulin-like growth factor-1 (IGF-1) was shown to enhance retinal endothelial
      glucose transport in a process that is dependent on protein kinase C (PKC) and
      phosphatidylinositol-3 kinase (PI3 kinase). In the current study, the role of
      mitogen-activated protein kinase (MAP kinase) in regulating IGF-1 effects on
      retinal endothelial cell glucose transport was investigated in a bovine retinal
      endothelial cell (BREC) culture model. IGF-1 (25 ng/mL) caused a rapid increase
      in MAP-kinase activity and ERK phosphorylation. Inhibition of MAP kinase with
      PD98059 (100 microm) blocked IGF-1 enhancement of 2-deoxyglucose uptake. In order
      to clarify the relationship between PKC, PI3 kinase and MAP kinase in IGF-1
      signaling in retinal endothelial cells, the effects of selective inhibitors of
      MAP kinase (PD98059), PKC (GF109203X), and PI3 kinase (wortmannin, LY294002) on
      signal transduction by IGF-1 were studied. Inhibition of MAP kinase abolished IGF
      1 stimulation of PKC but had no effect on PI3 kinase activity, whereas inhibition
      of either PKC and PI3 kinase had no effect on MAP kinase phosphorylation or
      activity in IGF-1-treated cells. Taken together, these data demonstrate that IGF
      1 stimulation of BREC glucose transport requires activation of MAP kinase and
      that MAP kinase is upstream from PKC but is independent of PI3 kinase in
      mediating the actions of IGF-1 on retinal endothelial cells.

PMID- 12065633
TI  - Protein synthesis in synaptosomes: a proteomics analysis.
AB  - A proteomics approach was used to identify the translation products of a unique
      synaptic model system, squid optic lobe synaptosomes. Unlike its vertebrate
      counterparts, this preparation is largely free of perikaryal cell fragments and
      consists predominantly of pre-synaptic terminals derived from retinal
      photoreceptor neurones. We metabolically labelled synaptosomes with [(35)S]
      methionine and applied two-dimensional gel electrophoresis to resolve newly
      synthesized proteins at high resolution. Autoradiographs of blotted two
      dimensional gels revealed de novo synthesis of about 80 different proteins, 18 of
      which could be matched to silver-stained gels that were run in parallel. In-gel
      digestion of the matched spots and mass spectrometric analyses revealed the
      identities of various cytosolic enzymes, cytoskeletal proteins, molecular
      chaperones and nuclear-encoded mitochondrial proteins. A number of novel proteins
      (i.e. not matching with database sequences) were also detected. In situ
      hybridization was employed to confirm the presence of mRNA and rRNA in
      synaptosomes. Together, our data show that pre-synaptic endings of squid
      photoreceptor neurones actively synthesize a wide variety of proteins involved in
      synaptic functioning, such as transmitter recycling, energy supply and synaptic
      architecture.

PMID- 12065634
TI  - Regulation of cAMP-specific phosphodiesterases type 4B and 4D (PDE4) splice
      variants by cAMP signaling in primary cortical neurons.
AB  - This study examined the regulation of all known phosphodiesterase (PDE) type
      PDE4A, PDE4B and PDE4D splice variants in cortical neurons by cAMP signaling.
      Treatment with dibutyryl-cAMP (db-cAMP) caused the induction of two of the known
      splice variants, PDE4B2 and PDE4D1/PDE4D2. Although the splice variants PDE4A1,
      PDE4A5/PDE4A10, PDE4B3, PDE4B1, PDE4D3 and PDE4D4 were present in cortical
      neurons, their mRNA was not regulated at the transcriptional level by db-cAMP. To
      assess the increase in PDE4B2 and PDE4D1/D2 mRNA expression, the promoters
      containing these genes were characterized. Transcription from both promoters was
      stimulated by db-cAMP. Because chronic antidepressant treatment increases PDE4B,
      and not PDE4D, mRNA expression, we focused on the regulation of the PDE4B2
      promoter by cAMP and CREB. Dominant negative mutants of CREB suppressed PDE4B2
      promoter activity and a constitutively active form of CREB robustly stimulated
      it. These data demonstrate that in cortical neurons, a short PDE4B2 intronic
      promoter is regulated by CREB, confers cAMP responsitivity and directs PDE4B2
      mRNA and protein expression.

PMID- 12065635
TI  - PSD-95 eliminates Src-induced potentiation of NR1/NR2A-subtype NMDA receptor
      channels and reduces high-affinity zinc inhibition.
AB  - The channel activity of NMDA receptors is regulated by phosphorylation by protein
      kinases and by interaction with other proteins. Recombinant NR1/NR2A subtype NMDA
      receptor channels are potentiated by the protein tyrosine kinase Src, an effect
      which is mediated by a reduction in the high-affinity, voltage-independent Zn(2+)
      inhibition. However, it has been reported that Src-induced potentiation of NMDA
      receptor currents in hippocampus neurons is not mediated by a reduction in Zn(2+)
      inhibition. The post-synaptic density protein PSD-95 interacts with the C
      terminus of NR2 subunits of the NMDA receptor. Here we demonstrate that PSD-95
      eliminates the Src-induced potentiation of NR1/NR2A channels expressed in oocytes
      and reduces the sensitivity of the channels to Zn(2+). Our results reveal that
      the absence of Src-induced potentiation of PSD-95-coupled NR1/NR2A channels is
      not to due to the reduced sensitivity of these channels to Zn(2+). These results
      indicate that PSD-95 functionally modulates NR1/NR2A channels and explain why Src
      induced potentiation of NMDA receptor currents in hippocampus neurons is not
      mediated by a reduction in Zn(2+) inhibition.

PMID- 12065636
TI  - Spermine modulation of the glutamate(NMDA) receptor is differentially responsive
      to conantokins in normal and Alzheimer's disease human cerebral cortex.
AB  - The pharmacology of the N -methyl-d-aspartate (NMDA) receptor site was examined
      in pathologically affected and relatively spared regions of cerebral cortex
      tissue obtained at autopsy from Alzheimer's disease cases and matched controls.
      The affinity and density of the [(3)H]MK-801 binding site were delineated along
      with the enhancement of [(3)H]MK-801 binding by glutamate and spermine. Maximal
      enhancement induced by either ligand was regionally variable; glutamate-mediated
      maximal enhancement was higher in controls than in Alzheimer's cases in
      pathologically spared regions, whereas spermine-mediated maximal enhancement was
      higher in controls in areas susceptible to pathological damage. These and other
      data suggest that the subunit composition of NMDA receptors may be locally
      variable. Studies with modified conantokin-G (con-G) peptides showed that Ala(7)
      con-G had higher affinity than Lys(7)-con-G, and also defined two distinct
      binding sites in controls. Nevertheless, the affinity for Lys(7)-con-G was higher
      overall in Alzheimer's brain than in control brain, whereas the reverse was true
      for Ala(7)-con-G. Over-excitation mediated by specific NMDA receptors might
      contribute to localized brain damage in Alzheimer's disease. Modified conantokins
      are useful for identifying the NMDA receptors involved, and may have potential as
      protective agents.

PMID- 12065637
TI  - Tissue transglutaminase differentially modulates apoptosis in a stimuli-dependent
      manner.
AB  - Tissue transglutaminase is a unique member of the transglutaminase family as it
      not only catalyzes a transamidating reaction, but also binds and hydrolyzes GTP
      and ATP. Tissue transglutaminase has been reported to be pro-apoptotic, however,
      conclusive evidence is still lacking. To elucidate the role of tissue
      transglutaminase in the apoptotic process human neuroblastoma SH-SY5Y cells were
      stably transfected with vector only (SH/pcDNA), wild-type tissue transglutaminase
      (SH/tTG) and tissue transglutaminase that has no transamidating activity but
      retains its other functions (SH/C277S). In these studies three different
      apoptotic stimuli were used osmotic stress, staurosporine treatment and heat
      shock to delineate the role of tissue transglutaminase as a transamidating enzyme
      in the apoptotic process. In SH/tTG cells, osmotic stress and staurosporine
      treatments resulted in significantly greater caspase-3 activation and apoptotic
      nuclear changes then in SH/pcDNA or SH/C277S cells. This potentiation of
      apoptosis in SH/tTG cells was concomitant with a significant increase in the in
      situ transamidating activity of tissue transglutaminase. However, in the heat
      shock paradigm, which did not result in any increase in the transamidating
      activity in SH/tTG cells, there was a significant attenuation of caspase-3
      activity, LDH release and apoptotic chromatin condensation in SH/tTG and SH/C277S
      cells compared with SH/pcDNA cells. These findings indicate for the first time
      that the effect of tissue transglutaminase on the apoptotic process is highly
      dependent on the type of the stimuli and how the transamidating activity of the
      enzyme is affected. Tissue transglutaminase facilitates apoptosis in response to
      stressors that result in an increase in the transamidating activity of the
      enzyme. However, when the stressors do not result in an increase in the
      transamidating activity of tissue transglutaminase, than tissue transglutaminase
      can ameliorate the apoptotic response through a mechanism that is independent of
      its transamidating function. Further, neither the phosphatidylinositol-3-kinase
      pathway nor the extracellular-regulated kinase pathway is downstream of the
      modulatory effects of wild-type tissue transglutaminase or C277S-tissue
      transglutaminase in the apoptotic cascade.

PMID- 12065638
TI  - ATP-driven, Na(+)-independent inward Cl- pumping in neuroblastoma cells.
AB  - In immature neurones, the steady-state intracellular Cl- concentration [Cl-](i)
      is generally higher than expected for passive distribution, and this is believed
      to be due to Na(+)-K(+)-2Cl(-) co-transport. Here, we show that N2a neuroblastoma
      cells, incubated in HEPES-buffered NaCl medium maintain a [Cl-](i) around 60 mm,
      two- to threefold higher than expected for passive distribution at a membrane
      potential of - 49 mV. When the cells were transferred to a Cl(-) -free medium,
      [Cl-](i) decreased quickly (t(1/2) < 5 min), suggesting a high Cl- permeability.
      When the intracellular ATP concentration was reduced to less than 1 mm by
      metabolic inhibitors, the initial rate of (36) Cl- uptake was strongly inhibited
      (60-65%) while steady-state [Cl-](i) decreased to 24 mm, close to the value
      predicted from the Nernst equilibrium. Moreover, after reduction of [ATP](i) and
      [Cl-](i) by rotenone, the subsequent addition of glucose led to a reaccumulation
      of Cl-, in parallel with ATP recovery. Internal bicarbonate did not affect Cl-
      pumping, suggesting that Cl-/HCO(3)(-) exchange does not significantly contribute
      to active transport. Likewise, Na(+) -K(+) -2Cl(-) co-transport also appeared to
      play a minor role: although mRNA for the NKCC1 form of the co-transporter was
      detected in N2a cells, neither the initial rate of (36)Cl- uptake nor steady
      state [Cl-](i) were appreciably decreased by 10 microm bumetanide or replacement
      of external Na(+) by choline. These results suggest that a highly active ATP
      dependent mechanism, distinct from Na(+) -K(+) -2Cl(-) co-transport, is
      responsible for most of the inward Cl- pumping in N2a cells.

PMID- 12065639
TI  - Patterns of gene expression are altered in the frontal and motor cortices of
      human alcoholics.
AB  - Alcoholism is a major health problem in Western countries, yet relatively little
      is known about the mechanisms by which chronic alcohol abuse causes the
      pathologic changes associated with the disease. It is likely that chronic
      alcoholism affects a number of signaling cascades and transcription factors,
      which in turn result in distinct gene expression patterns. These patterns are
      difficult to detect by traditional experiments measuring a few mRNAs at a time,
      but are well suited to microarray analyses. We used cDNA microarrays to analyze
      expression of approximately 10 000 genes in the frontal and motor cortices of
      three groups of chronic alcoholic and matched control cases. A functional
      hierarchy was devised for classification of brain genes and the resulting groups
      were compared based on differential expression. Comparison of gene expression
      patterns in these brain regions revealed a selective reprogramming of gene
      expression in distinct functional groups. The most pronounced differences were
      found in myelin-related genes and genes involved in protein trafficking.
      Significant changes in the expression of known alcohol-responsive genes, and
      genes involved in calcium, cAMP, and thyroid signaling pathways were also
      identified. These results suggest that multiple pathways may be important for
      neuropathology and altered neuronal function observed in alcoholism.

PMID- 12065640
TI  - Modification of tyrosine hydroxylase activity by chloral derived beta-carbolines
      in vitro.
AB  - Beta-carbolines have been suggested to be involved in the pathogenesis of
      Parkinson's disease as a result of their structural similarity to the neurotoxin
      N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The chloral-derived beta
      carboline derivative 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo)
      causes cell loss in neuronal and glial cell cultures and induces a slowly
      developing neurodegenerative process in rats. In our experiments, effects of
      TaClo and its derivatives 2-methyl-TaClo (2-Me-TaClo), and 1-dichloromethylene
      1,2,3,4-tetrahydro-beta-carboline (1-CCl(2) -THbetaC) on tyrosine hydroxylase
      (TH) activity were investigated in TH assays using homogenate preparations of the
      rat nucleus accumbens and recombinant human TH (hTH1). TH activity was determined
      in vitro by measuring l-DOPA production with HPLC-ECD. Using homogenate
      preparations, TaClo, 2-Me-TaClo, and 1-CCl(2) -THbetaC inhibited TH in
      concentrations of 0.1 mm, while 1-CCl(2) -THbetaC in low concentrations enhanced
      TH activity. When TH was activated by PACAP-27, TaClo, 2-Me-TaClo, or 1-CCl(2) 
      THbetaC also inhibited activated enzyme activity in high concentrations. However,
      in the case of 2-Me-TaClo and 1-CCl(2) -THbetaC a biphasic effect was observed
      with a marked increase of TH activity in the nanomolar range. In our experiments
      using recombinant hTH1, TaClo, 2-Me-TaClo, or 1-CCl(2) -THbetaC did not modify
      enzyme activity. After activation of hTH1 by PKA all the tetrahydro-beta
      carbolines investigated in this study decreased l-DOPA formation. We suggest that
      these beta-carbolines modulate dopamine synthesis by interacting with a protein
      kinase TH-activating system.

PMID- 12065641
TI  - Overexpression of the signaling adapter FRS2 reconstitutes the cell cycle deficit
      of a nerve growth factor non-responsive TrkA receptor mutant.
AB  - We have characterized the cell cycle deficit of a novel TrkA receptor mutant
      (TrkAS3) that fails to support nerve growth factor (NGF)-dependent cell cycle
      arrest and neurite outgrowth. TrkAS3 receptors fail to support an NGF-dependent
      increase in the expression of cyclin D1 and the cell cycle inhibitor,
      p21(Waf1/Cip1), two important regulators of G(1) /S transition, and do not down
      regulate expression of the G(2) /M phase marker, cdc2/cdk1, or the S phase
      marker, proliferating cell nuclear antigen. Moreover, NGF-activated TrkAS3
      receptors do not down-regulate cyclin-dependent kinase 4 phosphorylation of the
      retinoblastoma protein, essential for G(1) arrest, in comparison to NGF-activated
      wild-type TrkA. Collectively these data indicate that TrkAS3 receptors fail to
      support NGF-dependent G(1) arrest. Interestingly, ectopic expression of
      regulators of G(1) /S arrest, such as cyclin D1 or inhibitors of cell cycle
      (p21(Waf1/Cip1), p16(INK4A) ), or the fibroblast growth factor (FGF) receptor
      substrate-2 (FRS2) in cells expressing TrkAS3 reconstitutes NGF-dependent neurite
      outgrowth. Collectively, these data suggest a model in which NGF-stimulated TrkA
      dependent activation of FRS2 supports neurite outgrowth through a mechanism that
      likely involves the induction of p21(Waf1/Cip1) expression and the arrest of
      cells at G(1) /S.

PMID- 12065642
TI  - Regulation of DARPP-32 dephosphorylation at PKA- and Cdk5-sites by NMDA and AMPA
      receptors: distinct roles of calcineurin and protein phosphatase-2A.
AB  - Glutamatergic inputs from corticostriatal and thalamostriatal pathways have been
      shown to modulate dopaminergic signaling in neostriatal neurons. DARPP-32
      (dopamine- and cAMP-regulated phosphoprotein of M (r) 32 kDa) is a signal
      transduction molecule that regulates the efficacy of dopamine signaling in
      neostriatal neurons. Dopamine signaling is mediated in part through
      phosphorylation of DARPP-32 at Thr34 by cAMP-dependent protein kinase, and
      antagonized by phosphorylation of DARPP-32 at Thr75 by cyclin-dependent protein
      kinase 5. We have now investigated the effects of the ionotropic glutamate NMDA
      and AMPA receptors on DARPP-32 phosphorylation in neostriatal slices. Activation
      of NMDA and AMPA receptors decreased the state of phosphorylation of DARPP-32 at
      Thr34 and Thr75. The decrease in Thr34 phosphorylation was mediated through
      Ca(2+) -dependent activation of the Ca(2+) -/calmodulin-dependent phosphatase,
      calcineurin. In contrast, the decrease in Thr75 phosphorylation was mediated
      through Ca(2+) -dependent activation of dephosphorylation by protein phosphatase
      2A. The results provide support for a complex effect of glutamate on dopaminergic
      signaling through the regulation of dephosphorylation of different sites of DARPP
      32 by different protein phosphatases.

PMID- 12065643
TI  - NF-kappaB-mediated up-regulation of Bcl-X(S) and Bax contributes to cytochrome c
      release in cyanide-induced apoptosis.
AB  - Cyanide induces apoptosis through cytochrome c activated caspase cascade in
      primary cultured cortical neurons. The underlying mechanism for cytochrome c
      release from mitochondria after cyanide treatment is still unclear. In this
      study, the roles of endogenous Bcl-2 proteins in cyanide-induced apoptosis were
      investigated. After cyanide (100-500 microm) treatment for 24 h, two pro
      apoptotic Bcl-2 proteins, Bcl-X(S) and Bax were up-regulated as shown by western
      blot and RT-PCR analysis. The expression levels of two antiapoptotic Bcl-2
      proteins, Bcl-2 and Bcl-X(L), remained unchanged after cyanide treatment, whereas
      the mRNA levels of Bcl-X(S) and Bax began to increase within 2 h and their
      protein levels increased 6 h after treatment. NF-kappaB, a redox-sensitive
      transcription factor activated after cyanide treatment, is responsible for the up
      regulation of Bcl-X(S) and Bax. SN50, which is a synthetic peptide that blocks
      translocation of NF-kappaB from cytosol to nucleus, inhibited the up-regulation
      of Bcl-X(S) and Bax. Similar results were obtained using a specific kappaB decoy
      DNA. NMDA receptor activation and reactive oxygen species (ROS) generation are
      upstream events of NF-kappaB activation, as blockade of these two events by
      MK801, l-NAME or PBN inhibited cyanide-induced up-regulation of Bcl-X(S) and Bax.
      Up-regulation of pro-apoptotic Bcl-X(S) and Bax contributed to cyanide-induced
      cytochrome c release, because SN50 and a specific Bax antisense
      oligodeoxynucleotide significantly reduced release of cytochrome c from
      mitochondria as shown by western blot analysis. It was concluded that NF-kappaB
      mediated up-regulation of Bcl-X(S) and Bax is involved in regulating cytochrome c
      release in cyanide-induced apoptosis.

PMID- 12065644
TI  - Alpha7 nicotinic receptor activation inhibits ethanol-induced mitochondrial
      dysfunction, cytochrome c release and neurotoxicity in primary rat hippocampal
      neuronal cultures.
AB  - Primary hippocampal neuronal cultures exhibited a concentration- and time
      dependent loss of cells when exposed to ethanol (EtOH). EtOH-induced
      neurotoxicity was attenuated by 2,4-dimethoxybenzilidene anabaseine (DMXB) which
      selectively activates alpha7 nicotinic receptors in a concentration-dependent
      manner. We further investigated the mechanisms of the protective effect of DMXB
      on EtOH- induced neurotoxicity. We found that EtOH decreased the mitochondrial
      membrane potential and released cytochrome c from mitochondria at neurotoxic
      concentrations. DMXB (3 microm) attenuated both of these actions in a manner that
      was in turn blocked with the nicotinic antagonist methyllyconitine (MLA) 100 nm.
      Neither DMXB nor MLA alone affected these parameters. These results suggest that
      the neuroprotection conferred by alpha7 nicotinic receptor activation may be
      mediated, at least in part, through preventing the decrease in the mitochondrial
      membrane potential and the increase in the release of cytochrome c caused by
      EtOH.

PMID- 12065645
TI  - PI 3-kinase regulation of dopamine uptake.
AB  - The magnitude and duration of dopamine (DA) signaling is defined by the amount of
      vesicular release, DA receptor sensitivity, and the efficiency of DA clearance,
      which is largely determined by the DA transporter (DAT). DAT uptake capacity is
      determined by the number of functional transporters on the cell surface as well
      as by their turnover rate. Here we show that inhibition of phosphatidylinositol
      (PI) 3-kinase with LY294002 induces internalization of the human DAT (hDAT),
      thereby reducing transport capacity. Acute treatment with LY294002 reduced the
      maximal rate of [(3) H]DA uptake in rat striatal synaptosomes and in human
      embryonic kidney (HEK) 293 cells stably expressing the hDAT (hDAT cells). In
      addition, LY294002 caused a significant redistribution of the hDAT from the
      plasma membrane to the cytosol. Conversely, insulin, which activates PI 3-kinase,
      increased [(3)H]DA uptake and blocked the amphetamine-induced hDAT intracellular
      accumulation, as did transient expression of constitutively active PI 3-kinase.
      The LY294002-induced reduction in [(3)H]DA uptake and hDAT cell surface
      expression was inhibited by expression of a dominant negative mutant of dynamin
      I, indicating that dynamin-dependent trafficking can modulate transport capacity.
      These data implicate DAT trafficking in the hormonal regulation of dopaminergic
      signaling, and suggest that a state of chronic hypoinsulinemia, such as in
      diabetes, may alter synaptic DA signaling by reducing the available cell surface
      DATs.

PMID- 12065646
TI  - Involvement of glycogen synthase kinase-3beta and tau phosphorylation in neuronal
      Golgi disassembly.
AB  - The dissociation of the neuronal Golgi complex is a classical feature observed in
      neurodegenerative disorders including Alzheimer's disease. The goal of this study
      is to determine if the phosphorylation of tau protein is involved in neuronal
      Golgi disassembly. Primary cortical cultures were exposed to two Golgi toxins,
      brefeldin A (BFA) or nordihydroguaiaretic acid (NDGA). Immunocytochemical studies
      using the anti58 k antibody revealed that Golgi disassembly started in exposed
      neurons a few minutes after treatment. BFA and NDGA induced a rapid and transient
      increase in tau phosphorylation in a site-specific manner on immunoblots. In
      addition, the increase in tau phosphorylation directly correlated with a
      transient dissociation of tau from the cytoskeleton and a decrease of the
      acetylated tubulin. Furthermore, the activity of glycogen synthase kinase-3beta
      (GSK-3beta) increased transiently, as demonstrated by the kinase activity assay
      and by immunoblottings of serine-9 and tyrosine-216 phosphorylated of GSK-3beta.
      A decrease of the Akt phosphorylated form was also shown. The increase in tau
      phosphorylation was inhibited by the GSK-3beta inhibitor, lithium. Finally,
      morphometric studies showed that lithium partially blocked the Golgi disassembly
      caused by BFA or NDGA. Together these findings indicate that GSK-3beta activity
      and tau phosphorylation state are involved in the maintenance of the neuronal
      Golgi organization.

PMID- 12065647
TI  - Albumin promotes neuronal survival by increasing the synthesis and release of
      glutamate.
AB  - It is well known that the presence of albumin within the brain and the CSF is
      developmentally regulated. However, the physiological relevance of this
      phenomenon is not well established. We have previously shown that albumin
      specifically increases the flux of glucose and lactate through the pyruvate
      dehydrogenase reaction in astrocytes. Here we show that, in neurones, albumin
      also increases the oxidation of glucose and lactate through the pyruvate
      dehydrogenase-catalysed reaction, the final purpose of this being the synthesis
      of glutamate. Thus, in neurones, the presence of albumin strongly increased the
      synthesis and release of glutamate to the extracellular medium. Our results also
      suggest that glutamate release caused by albumin is designed to promote neuronal
      survival. Thus, under culture conditions in which neurones die by apoptosis, the
      presence of albumin promoted neuronal survival and maintained the differentiation
      programme of these cells, as judged by the expression of the axonal protein, GAP
      43. The effect of albumin on neuronal survival was counteracted by the presence
      of DNQX, an antagonist of non-NMDA-glutamate receptors, suggesting that the
      glutamate synthesized and released due to the presence of albumin is responsible
      for neuronal survival. In addition, the effect of albumin seemed to depend on the
      activity of the NGF receptor, TrkA, suggesting that the glutamate synthesized and
      released due to the presence of albumin promotes neuronal survival through the
      activity of TrkA.

PMID- 12065648
TI  - Oxidation of DOPAC by nitric oxide: effect of superoxide dismutase.
AB  - This study aimed to characterize the redox interaction between 3,4
      dihydroxyphenylacetic acid (DOPAC) and nitric oxide (.NO), and to assess the
      reductive and oxidative decay pathways of the DOPAC semiquinone originating from
      this interaction. The reaction between DOPAC and.NO led to the formation of the
      DOPAC semiquinone radical, detected by electron paramagnetic resonance (EPR) and
      stabilized by Mg(2+), and the nitrosyl anion detected as nitrosylmyoglobin. The
      EPR signal corresponding to the DOPAC semiquinone was modulated as follows: (i)
      it was suppressed by glutathione and ascorbic acid with the formation of new EPR
      spectra corresponding to the glutathionyl and ascorbyl radical, respectively;
      (ii) it was enhanced by Cu,Zn-superoxide dismutase; the enzyme also accelerated
      the decay of the semiquinone species to DOPAC quinone. These results are
      interpreted as a one-electron oxidation of DOPAC by.NO; the reductive decay of
      the semiquinone back to DOPAC was facilitated by reducing agents, such as
      glutathione and ascorbate, whereas the oxidative decay to DOPAC quinone was
      facilitated by superoxide dismutase. The latter effect is understood in terms of
      a reversible conversion of nitrosyl anion to.NO by the enzyme. The biological
      relevance of these reactions is also discussed in terms of the reactivity of
      peroxynitrite towards DOPAC as a model with implications for aerobic conditions.

PMID- 12065649
TI  - Modulation of synaptic signalling complexes by Homer proteins.
AB  - The number of neurotransmitter receptors in the postsynaptic membrane and their
      functional coupling to intracellular signalling cascades are important
      determinants of synaptic strength--and hence potential targets for plasticity
      related modulation. In this context, Homer/Vesl proteins have gained particular
      interest for three main reasons: (i) they constitute part of the molecular
      scaffold at postsynaptic densities of excitatory synapses in the mammalian brain;
      (ii) they physically link type-I metabotropic glutamate receptors to the
      postsynaptic density and to inositol 1,4,5-triphosphate receptors in the
      subsynaptic endoplasmic reticulum; and (iii) Homer-1a, which has been categorized
      as an immediate early gene isoform, exerts dominant-negative activity, suggesting
      that it is involved in activity dependent rearrangements at synaptic junctions.
      Although these fundamental aspects have been reviewed previously by Xiao et al.,
      this review will address primarily more recent studies on the regulation of Homer
      1a expression and on the role of Homer/Vesl proteins in spine morphogenesis and
      receptor targeting and signalling.

PMID- 12065650
TI  - The cytotoxicity of dopamine may be an artefact of cell culture.
AB  - Administration of L-DOPA is commonly used to treat Parkinson's disease, yet
      controversy continues as to whether the dopamine arising from it aggravates
      neuronal loss. Several authors have reported cytotoxic effects of L-DOPA and
      dopamine on cultured cells, but others have not. In this report using the rat
      pheochromocytoma cell line PC12 and the M14 human melanoma cell line we show that
      dopamine-mediated cell death is not specific for neuronal cells. Moreover, our
      data show that both L-DOPA and dopamine interact with commonly used cell culture
      media, undergoing oxidation to generate hydrogen peroxide and dopamine
      semiquinones/quinones. Catalase and reduced glutathione could protect against
      cytotoxicity. These results suggest that caution needs to be employed when using
      cell culture studies to predict effects of L-DOPA and/or dopamine in vivo because
      of the extracellular generation of reactive species in the culture media.

PMID- 12065651
TI  - Reciprocal regulation of calcium dependent and calcium independent cyclic AMP
      hydrolysis by protein phosphorylation.
AB  - The hydrolysis of cyclic nucleotide second messengers takes place through
      multiple cyclic nucleotide phosphodiesterases (PDEs). The significance of this
      diversification is not fully understood. Here we report the differential
      regulation of low K(m) Ca2+-activated (PDE1C) and Ca2+-independent, rolipram
      sensitive (PDE4) PDEs by protein phosphorylation in the neuroendocrine cell line
      AtT20. Incubation of cells with 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP)
      enhanced PDE4 and reduced PDE1C activity. These effects were blocked by H89
      indicating mediation by cAMP-dependent protein kinase (PKA), furthermore in
      broken cell preparations PKA produced the same reciprocal changes of PDE
      activities. Calyculin A, an inhibitor of protein phosphatases 1 and 2 A,
      stimulated PDE4 and enhanced the inhibitory effect of CPT-cAMP on PDE1C. The
      reduction of PDE1C activity was characterized by a marked attenuation of the
      activation by Ca2+/calmodulin. Stimulation of PDE4 activity by CPT-cAMP or
      calyculin A was attributable to PDE4D3 and these effects could also be reproduced
      in human embryonic kidney cells expressing epitope-tagged PDE4D3. Together, these
      data show reciprocal regulation of PDE1C and PDE4D by PKA, which represents a
      novel scheme for plasticity in intracellular signalling.

PMID- 12065652
TI  - Nordihydroguaiaretic acid potently breaks down pre-formed Alzheimer's beta
      amyloid fibrils in vitro.
AB  - Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation
      of beta-amyloid fibrils (fAbeta) from Abeta, as well as the degradation of pre
      formed fAbeta in the CNS would be attractive therapeutic objectives for the
      treatment of Alzheimer's disease (AD). We previously reported that
      nordihydroguaiaretic acid (NDGA) inhibited fAbeta formation from Abeta(1-40) and
      Abeta(1-42) dose-dependently in the range of 10-30 micromin vitro. Utilizing
      fluorescence spectroscopic analysis with thioflavin T and electron microscopic
      study, we show here that NDGA dose-dependently breaks down fAbeta(1-40) and
      fAbeta(1-42) within a few hours at pH 7.5 at 37 degrees C. At 4 h, the
      fluorescence of fAbeta(1-40) and fAbeta(1-42) incubated with 50 microm NDGA was
      5% and 10% of the initial fluorescence, respectively. The activity of NDGA to
      break down these fAbetas was observed even at a low concentration of 0.1 microm.
      At 1 h, many short, sheared fibrils were observed in the mixture incubated with
      50 microm NDGA, and at 4 h, the number of fibrils reduced markedly, and small
      amorphous aggregates were observed. We next compared the activity of NDGA to
      break down fAbeta(1-40) and fAbeta(1-42), with other molecules reported to
      inhibit fAbeta formation from Abeta and/or to degrade pre-formed fAbeta both in
      vivo and in vitro. At a concentration of 50 microm, the overall activity of the
      molecules examined in this study was in the order of: NDGA >> rifampicin =
      tetracycline > poly(vinylsulfonic acid, sodium salt) = 1,3-propanedisulfonic
      acid, disodium salt > beta-sheet breaker peptide (iAbeta5). In cell culture
      experiments, fAbeta disrupted by NDGA were less toxic than intact fAbeta, as
      demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assay. Although the mechanisms by which NDGA inhibits fAbeta formation from
      Abeta, as well as breaking down pre-formed fAbetain vitro, are still unclear,
      NDGA could be a key molecule for the development of therapeutics for AD.

PMID- 12065653
TI  - Altered glycosylation of acetylcholinesterase in APP (SW) Tg2576 transgenic mice
      occurs prior to amyloid plaque deposition.
AB  - Previous studies have shown that a minor glycoform of acetylcholinesterase (AChE)
      is increased in Alzheimer's disease brain and cerebrospinal fluid. This glycoform
      can be distinguished from other AChE species by its lack of binding to
      concanavalin A (Con A). In this study, the temporal relationship between AChE
      glycosylation and Abeta deposition was examined in Tg2576 mice. There was a
      significant (p < 0.05) difference in AChE glycosylation in Tg2576 mice compared
      with age-matched background strain control mice at 4 months of age. This
      difference in glycosylation was also observed in 8- and 12-month-old Tg2576 mice.
      In contrast, Abeta plaques were only seen in the Tg2576 mice at 12 months of age,
      and were not detected at 4 and 8 months of age. Soluble human-sequence Abeta was
      detected as early as 4 months of age in the transgenic mice. The altered AChE
      glycosylation was due to an increase in a minor AChE isoform, which did not bind
      Con A, similar to that previously observed to be increased in Alzheimer's disease
      brain and cerebrospinal fluid. The results demonstrate that in transgenic mice
      altered AChE glycosylation is associated with very early events in the
      development of AD-like pathology. The study supports the possibility that
      glycosylation may also be a useful biomarker of AD.

PMID- 12065655
TI  - Pharmacological characterization of cloned chicken neuropeptide Y receptors Y1
      and Y5.
AB  - The neuropeptide Y (NPY) receptor subtypes Y1 and Y5 are involved in the
      regulation of feeding and several other physiological functions in mammals. To
      increase our understanding of the origin and mechanisms of the complex NPY
      system, we report here the cloning and pharmacological characterization of
      receptors Y1 and Y5 in the first non-mammal, chicken (Gallus gallus). The
      receptors display 80-83% and 64-72% amino acid sequence identity, respectively,
      with their mammalian orthologues. The three endogenous ligands NPY, peptide YY
      (PYY) and pancreatic polypeptide (PP) have similar affinities as in mammals, i.e.
      NPY and PYY have subnanomolar affinity for both receptors whereas chicken PP
      bound with nanomolar affinity to Y5 but not to Y1. A notable difference to
      mammalian receptor subtypes is that the Y1 antagonist SR120819A does not bind
      chicken Y1, whereas BIBP3226 does. The Y5 antagonist CGP71863A binds to the
      chicken Y5 receptor. Anatomically, both Y1 and Y5 have high mRNA expression
      levels in the infundibular nucleus which is the homologous structure of the
      hypothalamic arcuate nucleus in mammals. These results suggest that some of the
      selective Y1 and Y5 antagonists developed in mammals can be used to study
      appetite regulation in chicken.

PMID- 12065654
TI  - Group IB secretory phospholipase A2 induces neuronal cell death via apoptosis.
AB  - Group IB secretory phospholipase A2 (sPLA2-IB) mediates cell proliferation, cell
      migration, hormone release and eicosanoid production via its receptor in
      peripheral tissues. In the CNS, high-affinity binding sites of sPLA2-IB have been
      documented. However, it remains obscure whether sPLA2-IB causes biologic or
      pathologic response in the CNS. To this end, we examined effects of sPLA2-IB on
      neuronal survival in primary cultures of rat cortical neurons. sPLA2-IB induced
      neuronal cell death in a concentration-dependent manner. This death was a delayed
      response requiring a latent time for 6 h; sPLA2-IB-induced neuronal cell death
      was accompanied with apoptotic blebbing, condensed chromatin, and fragmented DNA,
      exhibiting apoptotic features. Before cell death, sPLA2-IB liberated arachidonic
      acid (AA) and generated prostaglandin D2 (PGD2) from neurons. PGD2 and its
      metabolite, Delta12-PGJ2, exhibited neurotoxicity. Inhibitors of sPLA2 and
      cyclooxygenase-2 (COX-2) significantly suppressed not only AA release, but also
      PGD2 generation. These inhibitors significantly prevented neurons from sPLA2-IB
      induced neuronal cell death. In conclusion, we demonstrate a novel biological
      response, apoptosis, of sPLA2-IB in the CNS. Furthermore, the present study
      suggests that PGD2 metabolites, especially Delta12-PGJ2, might mediate sPLA2-IB
      induced apoptosis.

PMID- 12065656
TI  - Antagonists of protein kinase C inhibit rat retinal glutamate transport activity
      in situ.
AB  - Neuronal and glial high-affinity transporters regulate extracellular glutamate
      concentration, thereby terminating synaptic transmission and preventing neuronal
      excitotoxicity. Glutamate transporter activity has been shown to be modulated by
      protein kinase C (PKC) in cell culture. This is the first study to demonstrate
      such modulation in situ, by following the fate of the non-metabolisable glutamate
      transporter substrate, d-aspartate. In the rat retina, pan-isoform PKC inhibition
      with chelerythrine suppressed glutamate uptake by GLAST (glutamate/aspartate
      transporter), the dominant excitatory amino acid transporter localized to the
      glial Muller cells. This effect was mimicked by rottlerin but not by Go6976,
      suggesting the involvement of the PKCdelta isoform, but not PKCalpha, beta or
      gamma. Western blotting and immunohistochemical labeling revealed that the
      suppression of glutamate transport was not due to a change in transporter
      expression. Inhibition of PKCdelta selectively suppressed GLAST but not neuronal
      glutamate transporter activity. These data suggest that the targeting of specific
      glutamate transporters with isoform-specific modulators of PKC activity may have
      significant implications for the understanding of neurodegenerative conditions
      arising from compromised glutamate homeostasis, e.g. glaucoma and amyotrophic
      lateral sclerosis.

PMID- 12065657
TI  - Highly conserved and disease-specific patterns of carboxyterminally truncated
      Abeta peptides 1-37/38/39 in addition to 1-40/42 in Alzheimer's disease and in
      patients with chronic neuroinflammation.
AB  - Human lumbar CSF patterns of Abeta peptides were analysed by urea-based beta
      amyloid sodium dodecyl sulphate polyacrylamide gel electrophoresis with western
      immunoblot (Abeta-SDS-PAGE/immunoblot). A highly conserved pattern of
      carboxyterminally truncated Abeta1-37/38/39 was found in addition to Abeta1-40
      and Abeta1-42. Remarkably, Abeta1-38 was present at a higher concentration than
      Abeta1-42, being the second prominent Abeta peptide species in CSF. Patients with
      Alzheimer's disease (AD, n = 12) and patients with chronic inflammatory CNS
      disease (CID, n = 10) were differentiated by unique CSF Abeta peptide patterns
      from patients with other neuropsychiatric diseases (OND, n = 37). This became
      evident only when we investigated the amount of Abeta peptides relative to their
      total Abeta peptide concentration (Abeta1-x%, fractional Abeta peptide pattern),
      which may reflect disease-specific gamma-secretase activities. Remarkably,
      patients with AD and CID shared elevated Abeta1-38% values, whereas otherwise the
      patterns were distinct, allowing separation of AD from CID or OND patients
      without overlap. The presence of one or two ApoE epsilon4 alleles resulted in an
      overall reduction of CSF Abeta peptides, which was pronounced for Abeta1-42. The
      severity of dementia was significantly correlated to the fractional Abeta peptide
      pattern but not to the absolute Abeta peptide concentrations.

PMID- 12065658
TI  - Overexpression of alpha7 nicotinic acetylcholine receptor prevents G1-arrest and
      DNA fragmentation in PC12 cells after hypoxia.
AB  - We investigated the neuroprotective function of alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR) after transient hypoxia (12 h) and reoxygenation (0-72 h),
      comparing rat pheochromocytoma (PC12) cells overexpressing FLAG-tagged
      alpha7nAChR (alpha7pCMV cells) and control PC12 cells (non-transfected or
      transfected with vector only) in medium with and without nicotine. Plasma
      membrane degradation in the early phase after hypoxia was inhibited in PC12 cells
      with nicotine, and more profoundly in alpha7pCMV cells with nicotine. Inhibition
      of DNA fragmentation in the late phase after hypoxia was most remarkable in
      alpha7pCMV cells with nicotine, but, surprisingly, it was more remarkable in
      alpha7pCMV cells without nicotine than in PC12 cells with nicotine. G1-arrest of
      the cell cycle, observed in control PC12 cells at 12 h after hypoxia, preceding
      DNA fragmentation, was not evident in alpha7pCMV cells, with or without nicotine.
      Furthermore, in alpha7pCMV cells with and without nicotine, the basal expression
      levels of total Akt were approximately 1.5-fold higher, and the up-regulation of
      Akt phosphorylated at Ser473 after hypoxia was strikingly enhanced, compared with
      control PC12 cells. These findings suggest that alpha7nAChR functions
      constitutively in PC12 cells, that its overexpression raises tolerance against G1
      arrest and DNA fragmentation after hypoxia, and that it can be considered a
      candidate target for treatment against hypoxia-induced acute membrane degradation
      and delayed DNA fragmentation in neurons.

PMID- 12065659
TI  - Integrative nuclear FGFR1 signaling (INFS) pathway mediates activation of the
      tyrosine hydroxylase gene by angiotensin II, depolarization and protein kinase C.
AB  - The integrative nuclear FGFR1 signaling (INFS) pathway functions in association
      with cellular growth, differentiation, and regulation of gene expression, and is
      activated by diverse extracellular signals. Here we show that stimulation of
      angiotensin II (AII) receptors, depolarization, or activation protein kinase C
      (PKC) or adenylate cyclase all lead to nuclear accumulation of fibroblast growth
      factor 2 (FGF-2) and FGFR1, association of FGFR1 with splicing factor-rich
      domains, and activation of the tyrosine hydroxylase (TH) gene promoter in bovine
      adrenal medullary cells (BAMC). The up-regulation of endogenous TH protein or a
      transfected TH promoter-luciferase construct by AII, veratridine, or PMA (but not
      by forskolin) is abolished by transfection with a dominant negative FGFR1TK
      mutant which localizes to the nucleus and plasma membrane, but not by
      extracellularly acting FGFR1 antagonists suramin and inositolhexakisphosphate
      (IP6). Mechanism of TH gene activation by FGF-2 and FGFR1 was further
      investigated in BAMC and human TE671 cultures. TH promoter was activated by co
      transfected HMW FGF-2 (which is exclusively nuclear) but not by cytoplasmic FGF-1
      or extracellular FGFs. Promoter transactivation by HMWFGF-2 was accompanied by an
      up-regulation of FGFR1 specifically in the cell nucleus and was prevented
      FGFR1(TK-) but not by IP6 or suramin. The TH promoter was also transactivated by
      co-transfected wild-type FGFR1, which localizes to both to the nucleus and the
      plasma membrane, and by an exclusively nuclear, soluble FGFR1(SP-/NLS) mutant
      with an inserted nuclear localization signal. Activation of the TH promoter by
      nuclear FGFR1 and FGF-2 was mediated through the cAMP-responsive element (CRE)
      and was associated with induction of CREB- and CBP/P-300-containing CRE
      complexes. We propose a new model for gene regulation in which nuclear FGFR1 acts
      as a mediator of CRE transactivation by AII, cell depolarization, and PKC.

PMID- 12065660
TI  - Reduced number of unmyelinated sensory axons in peripherin null mice.
AB  - Peripherin is a type III intermediate filament (IF) abundantly expressed in
      developing neurons, but in the adult, it is primarily found in neurons extending
      to the peripheral nervous system. It has been suggested that peripherin may play
      a role in axonal elongation and/or cytoskeletal stabilization during development
      and regeneration. To further clarify the function of peripherin, we generated and
      characterized mice with a targeted disruption of the peripherin gene. The
      peripherin null mice were viable, reproduced normally and did not exhibit overt
      phenotypes. Microscopic analysis revealed no gross morphological defects in the
      ventral and dorsal roots, spinal cord, retina and gut, but protein analyses
      showed increased levels of the type IV IF alpha-internexin in ventral roots of
      peripherin null mice. Whereas the number and caliber of myelinated motor and
      sensory axons in the L5 roots remained unchanged in peripherin knockout mice,
      there was a substantial reduction ( approximately 34%) in the number of L5
      unmyelinated sensory fibers that correlated with a decreased binding of the
      lectin IB4. These results demonstrate a requirement of peripherin for the proper
      development of a subset of sensory neurons.

PMID- 12065661
TI  - Norepinephrine triggers Ca2+-dependent exocytosis of 5-hydroxytryptamine from rat
      pinealocytes in culture.
AB  - 5-hydroxytryptamine (5-HT) is a precursor and a putative modulator for melatonin
      synthesis in mammalian pinealocytes. 5-HT is present in organelles distinct from
      l-glutamate-containing synaptic-like microvesicles as well as in the cytoplasm of
      pinealocytes, and is secreted upon stimulation by norepinephrine (NE) to enhance
      serotonin N-acetyltransferase activity via the 5-HT2 receptor. However, the
      mechanism underlying the secretion of 5-HT from pinealocytes is unknown. In this
      study, we show that NE-evoked release of 5-HT is largely dependent on Ca2+ in rat
      pinealocytes in culture. Omission of Ca2+ from the medium and incubation of
      pineal cells with EGTA-tetraacetoxymethyl-ester inhibited by 59 and 97% the NE
      evoked 5-HT release, respectively. Phenylephrine also triggered the Ca2+
      dependent release of 5-HT, which was blocked by phentolamine, an alpha
      antagonist, but not by propranolol, a beta antagonist. Botulinum neurotoxin type
      E cleaved 25 kDa synaptosomal-associated protein and inhibited by 50% of the NE
      evoked 5-HT release. Bafilomycin A1, an inhibitor of vacuolar H+-ATPase, and
      reserpine and tetrabenazine, inhibitors of vesicular monoamine transporter, all
      decreased the storage of vesicular 5-HT followed by inhibition of the NE-evoked 5
      HT release. Agents that trigger L-glutamte exocytosis such as acetylcholine did
      not trigger any Ca2+-dependent 5-HT release. Vice versa neither NE nor
      phenylephrine caused synaptic-like microvesicle-mediated l-glutamate exocytosis.
      These results indicated that upon stimulation of a adrenoceptors pinealocytes
      secrete 5-HT through a Ca2+-dependent exocytotic mechanism, which is distinct
      from the exocytosis of synaptic-like microvesicles.

PMID- 12065662
TI  - The effects of focal ischemia and reperfusion on the glutathione content of
      mitochondria from rat brain subregions.
AB  - Glutathione is a key cellular antioxidant that is contained in both cytoplasmic
      and mitochondrial compartments. Previous investigations indicate that depletion
      of the mitochondrial pool of glutathione can greatly reduce cell viability. In
      the present investigation, the effect of focal cerebral ischemia on total
      (reduced plus oxidized) glutathione in mitochondria was assessed using a rat
      model of middle cerebral artery occlusion. Total glutathione was substantially
      decreased in mitochondria prepared from severely ischemic focal tissue in both
      the cerebral cortex and striatum at 2 h of vessel occlusion and persisted for at
      least the first 3 h of reperfusion. The loss of mitochondrial glutathione was not
      associated with decreases of the total tissue glutathione content and was not due
      to the formation of mixed disulfides with mitochondrial proteins. Thus, an
      imbalance between uptake and release from the mitochondria in the ischemic tissue
      provides the most likely explanation for the loss. Decreases in glutathione also
      developed in mitochondria from the moderately ischemic perifocal tissue when the
      period of arterial occlusion was extended to 3 h. The presence of mitochondrial
      glutathione depletion during ischemia showed an apparent close association with
      the subsequent development of tissue infarction. These findings are consistent
      with a role for the glutathione depletion in determining the susceptibility of
      brain tissue to focal ischemia.

PMID- 12065663
TI  - Adenosine inhibits calcium channel currents via A1 receptors on salamander
      retinal ganglion cells in a mini-slice preparation.
AB  - The effects of adenosine on high-voltage-activated calcium channel currents in
      tiger salamander retinal ganglion cells were investigated in a mini-slice
      preparation. Adenosine produced a concentration-dependent decrease in the
      amplitude of calcium channel current with a maximum inhibition of 26%. The
      effects of adenosine on calcium channel current were both time- and voltage
      dependent. In cells dialyzed with GTP-gamma-s, adenosine caused a sustained and
      irreversible inhibition of calcium channel current, suggesting involvement of a
      GTP-binding protein. The inhibitory effect of adenosine on calcium channel
      current was blocked by the A1 antagonist 8-cyclopentyltheophylline (DPCPX, 1-10
      microm), but not by the A2 antagonist 3-7-dimethyl-1-propargylxanthine (DMPX, 10
      microm), and was mimicked by the A1 agonist N6-cyclohexyladenosine (CHA, 1
      microm) but not by the A2 agonist 5'-(N-cyclopropyl) carbox-amidoadenosine (CPCA,
      1 microm). Adenosine's inhibition of calcium channel current was not affected by
      the L-type calcium channel blocker nifedipine (5 microm). However, adenosine's
      inhibition of calcium channel current was reduced to approximately 10% after
      application of omega-conotoxin GVIA (1 microm), suggesting that adenosine
      inhibits N-type calcium channels. These results show that adenosine acts on an A1
      adenosine receptor subtype via a G protein-coupled pathway to inhibit the
      component of calcium channel current carried in N-type calcium channels.

PMID- 12065664
TI  - The RNA-binding protein Staufen from rat brain interacts with protein phosphatase
      1.
AB  - In mammalian neurones, homologues of the Drosophila RNA-binding protein Staufen
      are part of ribonucleoprotein complexes that move bidirectionally along dendritic
      microtubules and appear to regulate mRNA translocation and translation. In this
      study, putative components of Staufen granules were identified in a yeast two
      hybrid screen of a rat brain cDNA library with a rat Staufen bait. Protein
      phosphatase-1 was found as an interacting partner. Binding appears to be mediated
      by a five amino acid residue sequence motif (R-K-V-T-F) in Staufen that is
      conserved in a number of proteins interacting with the phosphatase. A two amino
      acid residue mutation within this motif (R-K-V-G-A) disrupted the interaction. A
      cytoplasmic interaction of both proteins was shown by coimmunoprecipitation of
      rat Staufen and protein phosphatase-1 from the cytoplasm of transfected cells and
      rat brain homogenates. In mammalian brain, the phosphatase represents the first
      described endogenous interaction partner of Staufen. In primary hippocampal
      neurones, both proteins partially colocalize in somata and neuronal processes.
      Staufen does not modulate the in vitro protein phosphatase activity. These
      findings show that protein phosphatase-1 is a native component of Staufen
      particles. Cellular functions of Staufen may be regulated via phosphorylation or
      Staufen may recruite the phosphatase into specific ribonucleoprotein complexes.

PMID- 12065665
TI  - Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and
      PC2 in the maturation of VGF precursor.
AB  - The neurotrophin responsive gene vgf is widely expressed in central and
      peripheral neurones, and in certain neuroendocrine cell populations. Its encoded
      VGF precursor protein (proVGF1: 617 amino acids in rat, 615 in man, > 85%
      homology) gives rise to several low molecular weight species. We studied a range
      of neuroendocrine and neuronal cells, in which VGF-processing products were
      prominent with an apparent molecular weight of 20 and 10 kDa (VGF20 and VGF10,
      respectively). Such peptides were recognized by antibodies specific for the C
      terminal rat VGF nonapeptide, thus indicating that they included the C-terminus
      of proVGF. Ectopic expression of the neuroendocrine-specific prohormone
      convertases PC1/3 or PC2 in GH3 cells showed that both could generate VGF20,
      while VGF10 was preferentially produced by PC1/3. Site-directed mutagenesis was
      used to identify the KRKRKK(488) motif as the target within VGF sequence which
      leads to the production of VGF20. Molecular characterization of rat VGF10, on the
      other hand, revealed that this peptide is produced by cleavage at the RPR(555)
      site. By the combined use of high-resolution separation techniques, matrix
      assisted laser desorption/ionization time of flight (MALDI-ToF) mass spectrometry
      and manual Edman degradation we identified in rat brain a VGF fragment analogous
      to bovine peptide V and two novel peptides also derived from the C-terminal
      region of proVGF.

PMID- 12065666
TI  - A novel seven transmembrane receptor induced during the early steps of astrocyte
      differentiation identified by differential expression.
AB  - The rat glial progenitor cell line CG-4 can be induced to differentiate into
      either oligodendrocytes or type-2 astrocytes. In order to identify genes whose
      expression varies coincident with such phenotypic differentiation, we employed
      representational difference analysis (RDA) of mRNA. Here, we report 38 cDNAs
      induced in type-2 astrocytes, oligodendrocytes, or both differentiated states.
      Among these were known transcription factors, membrane receptors, extracellular
      matrix proteins, secreted signaling modulators, chromatin regulators and myelin
      sheath components. In addition several novel genes were identified; among these
      was a gene induced during the very early stages of astrocyte differentiation that
      we have named Ieda (induced early in differentiating astrocytes). Several Ieda
      transcripts were detected by RT-PCR, and appeared to be produced by alternative
      splicing and promoter usage. The protein deduced from the longest Ieda mRNA
      exhibited sequence features characteristic of G-protein coupled receptors,
      including seven putative transmembrane domains, while the shorter Ieda
      transcripts encoded proteins that lacked several transmembrane segments. In the
      adult rat, Ieda transcripts were found exclusively in brain and testis. In the
      developing rat brain, Ieda expression was first detected at embryonic day 16,
      that is two days before the first appearance of mature astrocytes. Thus, this
      approach has yielded a potential source of markers for differentiation states of
      these two cellular types as well as genes predicted to be functionally involved
      in the differentiation process itself.

PMID- 12065667
TI  - Lack of regulation of aromatic L-amino acid decarboxylase in intact bovine
      chromaffin cells.
AB  - Aromatic l-amino acid decarboxylase (AADC) is the second enzyme in the
      catecholamine biosynthetic pathway, and its activity is generally considered not
      to be limiting, and therefore not involved, in regulating flux through this
      pathway. Recent studies showing that its activity can be regulated in vivo and
      that the enzyme can be phosphorylated and activated in vitro have raised the
      possibility that AADC may play more than an obligatory role in catecholamine
      biosynthesis. In the present study, the phosphorylation and activity of AADC was
      evaluated relative to that of tyrosine hydroxylase (TH; the first and rate
      limiting enzyme in the pathway) in intact bovine chromaffin cells. Treatment of
      chromaffin cells with elevated potassium, acetylcholine, phorbol dibutyrate,
      forskolin, or okadaic acid each increased 32P incorporation into TH (after
      metabolic labeling of ATP pools with 32P(i)) and TH activity. In contrast, as
      measured in matched samples, 32P incorporation into AADC was not detected and
      none of the treatments altered AADC activity. Thus, that AADC can be
      phosphorylated and activated in vitro has questionable physiological
      significance.

PMID- 12065668
TI  - p75 neurotrophin receptor is required for constitutive and NGF-induced survival
      signalling in PC12 cells and rat hippocampal neurones.
AB  - We have previously shown that nerve growth factor (NGF)-induced activation of
      nuclear factor-kappaB increased neuronal expression of Bcl-xL, an anti-apoptotic
      Bcl-2 family protein. In the present study we determined the role of the p75
      neurotrophin receptor in constitutive and NGF-induced survival signalling.
      Treatment of rat pheochromocytoma (PC12) cells with a blocking anti-rat p75
      antibody or inhibition of p75 expression by antisense oligonucleotides reduced
      constitutive and NGF-induced bcl-xL expression. Treatment with the blocking anti
      p75 antibody also inhibited NGF-induced activation of the survival kinase Akt.
      Inhibition of phosphatidylinositol-3-kinase (PI3 kinase) activity or
      overexpression of a dominant-negative mutant of Akt kinase inhibited NGF-induced
      nuclear factor-kappaB activation. Activation of Akt kinase by NGF was also
      observed in PC12nnr5 cells and cultured rat hippocampal neurones which both lack
      significant TrkA expression. Treatment of hippocampal neurones with the blocking
      anti-p75 antibody inhibited constitutive and NGF-induced Bcl-xL expression,
      activation of Akt, and blocked the protective effect of NGF against excitotoxic
      and apoptotic injury. Our data suggest that the p75 neurotrophin receptor
      mediates constitutive and NGF-induced survival signalling in PC12 cells and
      hippocampal neurones, and that these effects are mediated via the PI3-kinase
      pathway.

PMID- 12065669
TI  - Intracellular Ca2+ signals evoked by stimulation of nicotinic acetylcholine
      receptors in SH-SY5Y cells: contribution of voltage-operated Ca2+ channels and
      Ca2+ stores.
AB  - Neuronal nicotinic acetylcholine receptors (nAChR) can regulate several neuronal
      processes through Ca2+-dependent mechanisms. The versatility of nAChR-mediated
      responses presumably reflects the spatial and temporal characteristics of local
      changes in intracellular Ca2+ arising from a variety of sources. The aim of this
      study was to analyse the components of nicotine-evoked Ca2+ signals in SH-SY5Y
      cells, by monitoring fluorescence changes in cells loaded with fluo-3 AM.
      Nicotine (30 microm) generated a rapid elevation in cytoplasmic Ca2+ that was
      partially and additively inhibited (40%) by alpha7 and alpha3beta2* nAChR subtype
      selective antagonists; alpha3beta4* nAChR probably account for the remaining
      response (60%). A substantial blockade (80%) by CdCl2 (100 microm) indicates that
      voltage-operated Ca2+ channels (VOCC) mediate most of the nicotine-evoked
      response, although the alpha7 selective antagonist alpha-bungarotoxin (40 nm)
      further decreased the CdCl2- resistant component. The elevation of intracellular
      Ca2+ levels provoked by nicotine was sustained for at least 10 min and required
      the persistent activation of nAChR throughout the response. Intracellular Ca2+
      stores were implicated in both the initial and sustained nicotine-evoked Ca2+
      responses, by the blockade observed after ryanodine (30 microm) and the
      inositoltriphosphate (IP3)-receptor antagonist, xestospongin-c (10 microm). Thus,
      nAChR subtypes are differentially coupled to specific sources of Ca2+: activation
      of nAChR induces a sustained elevation of intracellular Ca2+ levels which is
      highly dependent on the activation of VOCC, and also involves Ca2+ release from
      ryanodine and IP3-dependent intracellular stores. Moreover, the alpha7, but not
      alpha3beta2* nAChR, are responsible for a fraction of the VOCC-independent
      nicotine-evoked Ca2+ increase that appears to be functionally coupled to
      ryanodine sensitive Ca2+ stores.

PMID- 12065671
TI  - Inhibitors of nitric oxide synthase attenuate nerve growth factor-mediated
      increases in choline acetyltransferase expression in PC12 cells.
AB  - NGF can regulate nitric oxide synthase (NOS) expression and nitric oxide (NO) can
      modulate NGF-mediated neurotrophic responses. To investigate the role of NO in
      NGF-activated expression of cholinergic phenotype, PC12 cells were treated with
      either the nonselective NOS inhibitor L-NAME (N (omega)-nitro-L-arginine
      methylester) or the inducible NOS selective inhibitor MIU (s-methylisothiourea),
      and the effect on NGF-stimulated ChAT mRNA levels and ChAT specific activity was
      determined. NGF increased steady-state levels of mRNA and protein for both
      inducible and constitutive isozymes of NOS in PC12 cells, and led to enhanced NOS
      activity and NO production. MIU and, to a lesser extent, L-NAME blocked neurite
      outgrowth in nerve growth factor (NGF)-treated PC12 cells. Both L-NAME and MIU
      attenuated NGF-mediated increases in choline transferase (ChAT)-specific activity
      and prevented the increase in expression of ChAT mRNA normally produced by NGF
      treatment of PC12 cells. The present study indicates that NO may be involved in
      the modulation of signal transduction pathways by which NGF leads to increased
      ChAT gene expression in PC12 cells.

PMID- 12065670
TI  - Impact of endogenous nitric oxide on microglial cell energy metabolism and labile
      iron pool.
AB  - Microglial activation is common in several neurodegenerative disorders. In the
      present study, we used the murine BV-2 microglial cell line stimulated with gamma
      interferon and lipopolysaccharide to gain new insights into the effects of
      endogenously produced NO on mitochondrial respiratory capacity, iron regulatory
      protein activity, and redox-active iron level. Using polarographic measurement of
      respiration of both intact and digitonin-permeabilized cells, and
      spectrophotometric determination of individual respiratory chain complex
      activity, we showed that in addition to the reversible inhibition of cytochrome-c
      oxidase, long-term endogenous NO production reduced complex-I and complex-II
      activities in an irreversible manner. As a consequence, the cellular ATP level
      was decreased in NO-producing cells, whereas ATPase activity was unaffected. We
      show that NO up-regulates RNA-binding of iron regulatory protein 1 in microglial
      cells, and strongly reduces the labile iron pool. Together these results point to
      a contribution of NO derived from inflammatory microglia to the misregulation of
      energy-producing reactions and iron metabolism, often associated with the
      pathogenesis of neurodegenerative disorders.

PMID- 12065672
TI  - Mass-spectrometric analysis of myelin proteolipids reveals new features of this
      family of palmitoylated membrane proteins.
AB  - In this study, we have investigated the structure of the native myelin
      proteolipid protein (PLP), DM-20 protein and several low molecular mass
      proteolipids by mass spectrometry. The various proteolipid species were isolated
      from bovine spinal cord by size-exclusion and ion-exchange chromatography in
      organic solvents. Matrix-assisted laser desorption ionization-time of flight-mass
      spectrometry (MALDI-TOF-MS) of PLP and DM-20 revealed molecular masses of 31.6
      and 27.2 kDa, respectively, which is consistent with the presence of six and four
      molecules of thioester-bound fatty acids. Electrospray ionization-MS analysis of
      the deacylated proteins in organic solvents produced the predicted molecular
      masses of the apoproteins (29.9 and 26.1 kDa), demonstrating that palmitoylation
      is the major post-translational modification of PLP, and that the majority of PLP
      and DM-20 molecules in the CNS are fully acylated. A series of myelin-associated,
      palmitoylated proteolipids with molecular masses raging between 12 kDa and 18 kDa
      were also isolated and subjected to amino acid analysis, fatty acid analysis, N-
      and C-terminal sequencing, tryptic digestion and peptide mapping by MALDI-TOF-MS.
      The results clearly showed that these polypeptides correspond to the N-terminal
      region (residues 1-105/112) and C-terminal region (residues 113/131-276) of the
      major PLP, and they appear to be produced by natural proteolytic cleavage within
      the 60 amino acid-long cytoplasmic domain. These proteolipids are not postmortem
      artifacts of PLP and DM-20, and are differentially distributed across the CNS.

PMID- 12065673
TI  - Expression of Cdk5 and its activators in NT2 cells during neuronal
      differentiation.
AB  - We have recently developed a rapid protocol involving NT2 cell aggregation and
      treatment with retinoic acid (RA) to produce terminally differentiated CNS
      neurons. As a first step to explore the functional roles of cell-cycle regulatory
      proteins in the process of neuronal differentiation, the expression profiles of
      cyclin-dependent kinases (Cdks) and their regulators were examined in NT2 cells
      following treatment with RA. One of the Cdks, Cdk5, has been demonstrated to
      affect the process of neuronal differentiation and suggested to play an important
      role in development of the nervous system. We found that the expression of Cdk5
      was gradually increased, while its activators (p35 and p39) as well as Cdk5
      kinase activity were induced in NT2 cells during the process of neuronal
      differentiation. Moreover, both p35 and p39 were localized along the axons and
      varicosity-like structures of differentiated NT2 neurons. Taken together, our
      results demonstrated that NT2 cells provide a good in vitro model system to
      examine signaling pathways involved in the regulation of Cdk5 activators and to
      elucidate the functional roles of Cdk5 in neuronal differentiation.

PMID- 12065674
TI  - Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model
      of Alzheimer's disease (APPsw).
AB  - Alzheimer's disease neuropathology is characterised by beta-amyloid plaques and
      neurofibrillary tangles. Inhibition of beta-amyloid accumulation may be essential
      for effective therapy in Alzheimer's disease. In this study we have treated
      transgenic mice carrying the Swedish mutation of human amyloid precursor protein
      [Tg(Hu.APP695.K670N-M671L)2576], which develop brain beta-amyloid deposits, with
      nicotine in drinking fluid (200 microg/mL) from 9-14.5 months of age (5.5
      months). A significant reduction in amyloid beta peptide 1-42 positive plaques by
      more than 80% (p < 0.03) was observed in the brains of nicotine treated compared
      to sucrose treated transgenic mice. In addition, there was a selective reduction
      in extractable amyloid beta peptides in nicotine treated mice; cortical insoluble
      1-40 and 1-42 peptide levels were lower by 48 and 60%, respectively (p < 0.005),
      whilst there was no significant change in soluble 1-40 or 1-42 levels. The
      expression of glial fibrillary acidic protein was not affected by nicotine
      treatment. These results indicate that nicotine may effectively reduce amyloid
      beta peptide aggregation in brain and that nicotinic drug treatment may be a
      novel protective therapy in Alzheimer's disease.

PMID- 12065675
TI  - The neuropeptide FF analogue, 1DMe, reduces in vivo dynorphin release from the
      rat spinal cord.
AB  - Intrathecal infusion of the neuropeptide FF analogue, [D-Tyr1,
      (NMe)Phe3]neuropeptide FF (1DMe; 0.1 microm-0.1 mm) in anaesthetized rats
      produced a concentration-dependent decrease in the spinal outflow of dynorphin A
      (1-8)-like material, which persisted for at least 90 min after treatment with 10
      microm-0.1 mm of the compound. Co-administration of d-Phe-Cys-Tyr-D-Trp-Orn-Thr
      Pen-Thr-NH2 (CTOP; 1 microm) to block spinal micro-opioid receptors did not
      modify this effect, whereas naltrindole (10 microm) totally prevented it and nor
      binaltorphimine (10 microm) reduced the post-effect. These data suggest that 1DMe
      triggers the release of endogenous opioids that stimulate mainly delta-opioid
      receptors, and secondarily kappa-opioid receptors, thereby exerting a negative
      influence on dynorphin A (1-8)-like material outflow. Because dynorphin has
      pronociceptive properties, such a decrease in spinal dynorphin A (1-8)-like
      material release might underlie the long-lasting antinociceptive effects of
      intrathecally administered neuropeptide FF and analogues.

PMID- 12065677
TI  - Mechanisms of chronic renal allograft rejection. II. Progressive allograft
      glomerulopathy in miniature swine.
AB  - We have reported that in thymectomized miniature swine treated with a 12-day
      course of cyclosporin A that major histocompatibility complex class I-mismatched
      renal allografts either progress to chronic rejection (progression group; n = 4)
      or tolerance after acute rejection (recovery group; n = 4). Two types of
      glomerulopathies, termed acute and chronic allograft glomerulopathy, occur in
      allografts in this model. Morphological and immunohistochemical studies were
      performed on serial renal biopsies from both groups to examine the pathogenic
      mechanisms of acute and chronic allograft glomerulopathy. In acute rejection,
      acute allograft glomerulopathy developed in both groups by Day 18, with antibody
      deposition and T cell and macrophage infiltration. In situ DNA nick end-labeling
      (TUNEL)+ injured glomerular endothelial cells appeared from the early phase,
      followed by destruction of the glomerular capillary network with segmental
      mesangiolysis. Thereafter, in the progression group, acute allograft
      glomerulopathy progressed to chronic allograft glomerulopathy during the
      development of chronic rejection. This process was associated with persistent T
      cell and macrophage infiltration, antibody deposition, and TUNEL+ glomerular
      endothelial injury in the glomeruli. Impaired capillary repair, mesangial cell
      proliferation, and activation were still noted at Day 100, together with
      accumulation of mesangial matrix and duplication of glomerular basement membrane.
      In contrast, in the recovery group, acute allograft glomerulopathy recovered by
      Day 100, associated with the resolution of cellular infiltration and reduction of
      antibody deposition. We conclude that the acute and persistent cell- and antibody
      mediated rejection against glomerular endothelial cells is the key pathogenic
      determinant of acute allograft glomerulopathy and progression toward chronic
      allograft glomerulopathy. Impaired capillary repair and phenotypic change of
      endothelial and mesangial cells also contribute to the development of chronic
      allograft glomerulopathy. With the development of tolerance, substantial recovery
      of acute allograft glomerulopathy can occur after the resolution of glomerular
      inflammation.

PMID- 12065678
TI  - Heme oxygenase-1 modulates fetal growth in the rat.
AB  - Intrauterine growth restriction is associated with increased perinatal morbidity
      and mortality as well as with lifelong cardiovascular and metabolic
      complications. Deficiency of heme oxygenase 1 (HO-1) is associated with growth
      restriction in mice and in humans, suggesting a role for HO-1 in fetal growth and
      maintenance of pregnancy. We hypothesized that modulation of HO-1 in the pregnant
      rat would alter fetal growth. In pregnant dams, placental HO activity was
      significantly inhibited with zinc deuteroporphyrin IX 2,4 bis glycol, and HO-1
      protein was increased by transducing adenoviral human HO-1. Inhibition of HO-1 by
      zinc deuteroporphyrin IX 2,4 bis glycol resulted in a significant decrease in pup
      size, whereas transfection with hHO-1 resulted in increased pup size.
      Furthermore, the expression of IGF binding protein-1 and its receptor paralleled
      the expression of HO-1 in the placenta and were significantly modulated by
      modification of HO-1 along with the expression of vascular endothelial growth
      factor. These observations demonstrate that HO-1 modulates fetal growth by its
      effects on placental growth factors.

PMID- 12065679
TI  - Induction of p53 accumulation by Moloney murine leukemia virus-ts1 infection in
      astrocytes via activation of extracellular signal-regulated kinases 1/2.
AB  - SUMMARY: We previously reported that Moloney murine leukemia virus-ts1-mediated
      neuronal degeneration in mice is likely a result of both loss of glial support
      and release of cytokines and neurotoxins from ts1-infected glial cells. Viral
      infection in some cell types regulates expression of p53 protein, a key regulator
      of cell proliferation and death. Therefore, we hypothesized that p53 and its
      dependent genes may be linked with ts1-mediated neuropathology. We examined the
      presence of p53 and its dependent gene product, a proapoptotic protein bax-alpha,
      in ts1-induced spongiform encephalomyelopathy. Compared with controls, the
      lesions of infected animals contained increased levels of p53 and bax-alpha in
      astrocytes, as shown by strong nuclear p53 and cytoplasmic bax-alpha
      immunoreactivity in astrocytes. To determine how ts1 affects p53 expression in
      astrocytes, we then assessed the expression of p53 and its dependent genes, such
      as bax-alpha and p21, in infected and uninfected immortalized C1 astrocytes and
      studied possible pathways responsible for p53 accumulation in infected
      astrocytes. In these studies using mitogen-activated protein kinase inhibitors,
      infection-induced increases in the p53 level were partially blocked by PD98059, a
      synthetic inhibitor of MEK1 that is the immediate upstream kinase of
      extracellular signal-regulated kinases 1/2 (ERK1/2), but not by SB202190, a
      potent p38 kinase inhibitor. Furthermore, treatment with PD98059 significantly
      decreased the level of p21 protein, a p53-dependent gene product. These results
      suggest that ts1 infection may stabilize p53 protein through activation of ERKs
      in C1 astrocytes, leading to increased expression of the p21 and bax-alpha
      proteins, both of which induce cell cycle arrest and apoptosis. Our studies
      suggest that ts1 neuropathology in mice may result from changes in expression and
      activity of p53, brought about in part by ts1 activation of ERK.

PMID- 12065680
TI  - Glial cell line-derived neurotrophic factor family receptors are abnormally
      expressed in aganglionic bowel of a subpopulation of patients with Hirschsprung's
      disease.
AB  - Hirschsprung's disease (HSCR), a congenital disease, is characterized by the
      absence of ganglion cells in the ganglion plexuses of the caudal most gut. In the
      aganglionic colon, the plexus remnants are replaced by aggregates of glial cells
      and hypertrophied nerve fibers. Signaling of glial cell line-derived neurotrophic
      factor (GDNF)-GFRAs-receptor tyrosine kinase (RET) is crucial for the development
      and maintenance of ganglion cells. Mutations of genes such as GDNF and RET lead
      to the perturbation of this signaling pathway, which causes HSCR. To understand
      the role of GFRAs in ganglion cells and the pathogenesis of HSCR, we intended to
      determine the specific cell lineages in the enteric nervous system that normally
      express GFRAs but are affected in HSCR. We studied colon biopsy specimens from 13
      patients with HSCR (aged 1 day to 38 months) and 6 age-matched patients without
      HSCR as normal controls. RT-PCR, in situ hybridization, and immunohistochemistry
      were performed to examine the expression and cellular distributions of GFRAs in
      resected bowel segments of normal infants and those with HSCR. In normal infants
      and normoganglionic colon of patients with HSCR, the expression of GFRA1 was
      restricted to the glial cells and neurones of the ganglion plexuses. GFRAs
      expression was found to be markedly reduced in the aganglionic colons of 3
      infants with HSCR but was unaffected in the aganglionic colons of 10 other
      infants with HSCR. Residual GFRA expression was restricted to enteric glial cells
      in the plexus remnants of the aganglionic colons. Hypertrophied nerve fibers were
      not found to express GFRA1. We provide the first evidence that abnormal
      expression of GFRAs in the enteric nervous system may be involved in the
      pathogenesis of HSCR in a subpopulation of patients.

PMID- 12065682
TI  - Immortalization of human uterine leiomyoma and myometrial cell lines after
      induction of telomerase activity: molecular and phenotypic characteristics.
AB  - In vitro model systems for studying uterine leiomyomas are limited in that human
      derived leiomyoma cells grow poorly in culture compared with normal myometrial
      cells and begin to senesce early, at approximately passage 10 in our studies. To
      our knowledge, a good in vitro human-derived cell culturing system for leiomyomas
      does not exist. In an attempt to fill this void, we have immortalized a uterine
      leiomyoma cell line by inducing telomerase activity, which allows cells to bypass
      their normal programmed senescence. Telomerase activity was induced by infecting
      the target (uterine leiomyoma and normal myometrial) cells with a retroviral
      vector containing hTERT, the gene for the catalytic subunit of telomerase.
      Subsequent analysis by RT-PCR and the telomeric repeat amplification protocol
      assay confirmed expression of the inserted gene and induction of telomerase
      activity in leiomyoma and myometrial cells. Analysis of cells for estrogen
      receptor-alpha and progesterone receptor proteins by Western blotting showed no
      change in expression of these proteins between the immortalized and parental
      leiomyoma and myometrial cells. Both immortalized and parental myometrial and
      leiomyoma cells expressed the smooth muscle-specific cytoskeletal protein alpha
      actin and were negative for mutant p53 protein as evidenced by immunocytochemical
      staining. The immortalized leiomyoma and myometrial cells showed no anchorage
      independent growth, with the exception of a small subpopulation of immortalized
      leiomyoma cells at a higher passage that did form two to three small colonies
      (per 50,000 cells) in soft agar. None of the immortalized cells were tumorigenic
      in nude mice. In conclusion, our data show the successful insertion of the hTERT
      gene into leiomyoma and myometrial cells and the immortalization of these cell
      lines without phenotypic alteration from the parental cell types (up to 200
      population doublings). These cells should help to advance research in
      understanding the molecular pathways involved in the conversion of a normal
      myometrial cell to a leiomyoma cell and the mechanisms responsible for the growth
      of uterine leiomyomas. Answers to these questions will undoubtedly lead to the
      development of more effective treatment and intervention regimens for clinical
      cases of uterine leiomyoma.

PMID- 12065681
TI  - Podocyte-associated molecules in puromycin aminonucleoside nephrosis of the rat.
AB  - Molecules of central functional significance for the glomerular podocytes are
      rapidly emerging and have been shown to be distinctly involved in diseases with
      altered glomerular filtration barrier. Here we used the puromycin aminonucleoside
      (PA) nephrosis model in the rat to study some key proteins associated with the
      maintenance of the functional glomerular filtration barrier in vivo. The
      molecules studied included the filtration slit component nephrin, the hairpin
      like membrane protein podocin, the basolateral adhesion molecules beta1 integrin
      and alpha-dystroglycan, and the cytoskeleton-linking intermediary beta-catenin
      and the actin-associated alpha-actinin-4. The results showed diminished protein
      levels of podocin and nephrin in the PA-treated group. beta-catenin showed
      distinct down-regulation at 3 days of induction, and the control level was
      reached at 10 days. beta1 integrin was markedly up-regulated during induction.
      alpha-actinin-4 was not changed at the studied time points. The results show
      distinct differences in the different domains of podocytes during PA-induced
      proteinuria.

PMID- 12065683
TI  - Prediction of survival in stage I lung carcinoma patients by telomerase function
      evaluation.
AB  - Telomerase activity and telomerase reverse transcriptase (hTERT) expression are
      elevated in human malignancies. We have investigated telomerase activity measured
      by the telomeric repeat amplification protocol (TRAP) assay and hTERT levels by
      real-time RT-PCR in stage I non-small-cell lung carcinomas. The purposes of our
      study included the comparison of these two techniques in the assessment of
      telomerase function and the evaluation of their prognostic significance.
      Telomerase activity and hTERT levels were determined in 90 stage I non-small-cell
      lung carcinoma patients, using TRAP assay and real-time RT-PCR, respectively.
      Variables were analyzed by the chi(2) and Fisher exact tests. Survival was
      analyzed by the Kaplan-Meier method. Multivariate analysis was performed with the
      Cox's proportional hazards model. Telomerase activity was elevated in 60 (67%)
      carcinomas. hTERT was elevated in 43 (48%) carcinomas. Only 21 (23%) tumors had
      low telomerase function by both TRAP and hTERT expression levels. Telomerase
      activity and hTERT were significantly correlated (p = 0.017), although 35 cases
      displayed discordant results. Both telomerase activity and hTERT levels were
      significantly associated with poor patient overall and disease-free survival (p =
      0.019 and p = 0.018 for TRAP, and p = 0.011 and p = 0.012 for hTERT,
      respectively). Among the 21 patients with tumors displaying low telomerase
      function, defined by both TRAP and hTERT expression levels, only one succumbed to
      the disease (p = 0.0053). Our results suggest that the two techniques used in
      this study evaluate separate aspects of telomerase function and their combination
      provides powerful prognostic information in lung cancer patients.

PMID- 12065684
TI  - Common adult stem cells in the human breast give rise to glandular and
      myoepithelial cell lineages: a new cell biological concept.
AB  - Breast biology and pathology are currently shaped by the two-cell concept that
      recognizes only glandular and myoepithelial cells. In the present study, we have
      visualized a previously unidentified cell population within the epithelial
      compartment of the breast, which displays the phenotypic characteristics of a
      committed stem cell. Immunofluorescence double labeling with digital image
      processing and Western blotting were applied to normal breast tissue as well as
      to noninvasive and invasive breast cancers using antibodies to basal cytokeratin
      5 (Ck5), glandular cytokeratins 8/18 (Ck8/18/19), and smooth muscle alpha-actin
      (SMA) as markers for myoepithelial cells (SMA). A distinct population of cells
      was identified that expressed Ck5 in the absence of Ck8/18/19 or SMA. These cells
      differentiate toward glandular epithelial or myoepithelial Ck5-negative end cells
      passing through either Ck5/Ck8/18/19 or Ck5/SMA-positive intermediates. Our
      experiments clearly demonstrate a precursor or committed stem cell function of
      the Ck5-positive cell that is responsible for regeneration of the human adult
      breast epithelium. However, the observation that the vast majority of breast
      cancers display the glandular epithelial immunophenotype strongly suggests that
      the neoplastic cells derive from a late stage of the glandular epithelial
      differentiation pathway. The significance of this new cell biological model is
      that it might serve as a tool to unravel the regulatory mechanisms that govern
      regeneration and abnormal proliferation of breast epithelium at the cellular
      level.

PMID- 12065685
TI  - Angiotensin II angiogenic effect in vivo involves vascular endothelial growth
      factor- and inflammation-related pathways.
AB  - Although accumulating lines of evidence indicate the proangiogenic role of
      angiotensin II (Ang II), little is known about the molecular mechanisms
      associated with such an effect. This study aimed to identify molecular events
      involved in Ang II-induced angiogenesis in the Matrigel model in mice. C57Bl/6
      female mice received a subcutaneous injection of either Matrigel or Matrigel with
      Ang II (10(-7) M) alone, with Ang II and an AT1 receptor antagonist (candesartan,
      10(-6) M), or with Ang II and AT2 receptor antagonist (PD123319, 10(-6) M). After
      14 days, angiogenesis was assessed in the Matrigel-plug by histological
      evaluation and cellular counting. Ang II increased by 1.9-fold the number of
      cells within the Matrigel (p < 0.01 versus control). Immunohistological analysis
      revealed the presence of macrophages, endothelial and smooth muscle cells, and
      the development of vascular-like structure. Such an angiogenic effect was
      associated with an increase in vascular endothelial growth factor (VEGF) (1.5
      fold, p < 0.01), endothelial nitric oxide (eNOS) (1.7-fold, p < 0.01), and
      cyclooxygenase-2 (1.4-fold, p < 0.05) protein levels measured by Western
      blotting. Conversely, Ang II treatment did not affect MMP-9 and MMP-2 activity,
      assessed by zymography. Blockade of AT1 receptor completely prevented the Ang II
      induced angiogenesis and protein regulations, whereas that of AT2 was
      ineffective. Administration of VEGF neutralizing antibody (2.5 microg ip twice a
      week) and cyclooxygenase-2 selective inhibitor (nimesulide, 30 mg/L) also
      hampered Ang II proangiogenic effect. In addition, Ang II-induced cell ingrowth
      was impaired by treatment with nitric oxide synthase inhibitor (L-NAME, 10
      mg/kg/day) and in eNOS-deficient mice. Therefore, in an in vivo model, Ang II
      induced angiogenesis through AT1 receptor, which involved activation of VEGF/eNOS
      related pathway and of the inflammatory process.

PMID- 12065686
TI  - A novel localized amyloidosis associated with lactoferrin in the cornea.
AB  - We report a novel localized amyloidosis associated with lactoferrin. To elucidate
      the precursor protein of corneal amyloidosis associated with trichiasis, we
      analyzed amyloid deposits from three patients by histopathology and biochemistry.
      Amyloid deposits showed immunoreactivity, confirmed by electron microscopy, for
      only anti-human lactoferrin antibody. Electrophoresis of amyloid fibrils revealed
      lactoferrin with and without sugar chains; N-terminal sequence analysis revealed
      full-length lactoferrin and a truncated tripeptide of N-terminal amino acids, Gly
      Arg-Arg. Carboxymethylated wild-type lactoferrin formed amyloid fibrils in vitro.
      Lactoferrin gene analysis in the three patients revealed a Glu561Asp mutation in
      all of the patients and a compound heterozygote of Ala11Thr and Glu561Asp
      mutations in one patient. A heterozygotic Glu561Asp mutation appeared in 44.8% of
      healthy Japanese volunteers, suggesting that the mutation may not be an essential
      mutation for amyloid formation (p = 0.104). Results thus suggest that lactoferrin
      is this precursor protein.

PMID- 12065687
TI  - Effects and regulation of connective tissue growth factor on hepatic stellate
      cells.
AB  - Connective tissue growth factor (CTGF) is a 38-kd protein involved in several
      human fibrotic disorders including atherosclerosis and skin and renal fibrosis.
      Although it has been shown that human and experimental liver fibrosis is
      associated with CTGF expression through up-regulation of CTGF mRNA by hepatic
      stellate cells (HSC), the role of CTGF in the liver has not yet been determined.
      The aim of the present study was to assess the effects of CTGF on rat primary HSC
      and its regulation in a well-established model of in vitro liver fibrogenesis.
      Incubation of primary HSC with recombinant CTGF induced a significant migratory
      (2.3-fold, 50 ng/ml CTGF) and proliferative effect (1.8-fold, 100 ng/ml CTGF).
      Type I collagen mRNA expression, as assessed by a real-time RT-PCR procedure, was
      also increased when cells were incubated in the presence of CTGF (2-fold, 50
      ng/ml). Transforming growth factor-beta1 (TGF-beta1) strongly stimulated CTGF
      mRNA expression, a direct mechanism observed in the absence of any intermediate
      protein synthesis. Furthermore, spontaneous activation of HSC plated on plastic
      and stimulation by vascular endothelial growth factor, lipid peroxidation
      products (HNE, MDA), acetaldehyde, and platelet-derived growth factor (PDGF)-BB
      significantly up-regulated CTGF mRNA expression in HSC. PDGF-induced CTGF
      stimulation might be related in part to TGF-beta1 secretion because CTGF mRNA up
      regulation observed after PDGF-BB stimulation was abrogated in the presence of
      neutralizing TGF-beta1 antibody. In conclusion, this study extends the role of
      CTGF in HSC activation and suggests that CTGF up-regulation might be a central
      pathway during HSC activation.

PMID- 12065688
TI  - The cancer-testis gene, NY-ESO-1, is expressed in normal fetal and adult testes
      and in spermatocytic seminomas and testicular carcinoma in situ.
AB  - Cancer/testis genes are potential targets for therapeutic genetic and immunologic
      approaches, and are highly expressed in a large variety of human cancers.
      However, they are not expressed in normal tissues, with the exception of the
      testis. The NY-ESO-1 gene is the most recently identified member of the
      cancer/testis family and its product is one of the most immunogenic tumor
      antigens. We used immunohistochemistry to investigate the expression of NY-ESO-1
      in healthy human prenatal and adult testes and in 59 human testicular tumors of
      different subtypes. We found that NY-ESO-1 was expressed from 18 weeks until
      birth in human fetal testes. In the adult testis, NY-ESO-1 was strongly expressed
      in spermatogonia and in primary spermatocytes, but not in post-meiotic cells or
      in testicular somatic cells. NY-ESO-1 was not expressed in the Sertoli cells,
      Leydig cells, classical seminomas, or nonseminomatous germ cells in the 59
      testicular tumors. In contrast, NY-ESO-1 was expressed both in carcinomas in
      situ, which are the earliest stage of testicular tumors (7 of 15 cases), and in
      spermatocytic seminomas, which are believed to be derived from spermatogonia or
      primary spermatocytes (8 of 16 cases). We conclude that NY-ESO-1 is a marker that
      can be used to follow the early progression of testicular tumorigenesis when the
      tumors present a similar pattern of expression to the cells from which they
      originated, although the later tumors cease to express NY-ESO-1.

PMID- 12065689
TI  - In vivo cell lineage analysis during chemical hepatocarcinogenesis in rats using
      retroviral-mediated gene transfer: evidence for dedifferentiation of mature
      hepatocytes.
AB  - Feeding adult rats with a diet containing 2-acetylaminofluorene (2-AAF) results
      in suppression of hepatocyte proliferation and stimulation of oval cell
      proliferation. Although oval cells may be facultative liver stem cells, the
      actual relationship between oval cells and liver cancer has not been clearly
      established in vivo. Our goal was to label hepatic cells in vivo using retroviral
      vectors and follow their fate during the early steps of chemically induced
      hepatocarcinogenesis. Oval cell proliferation was induced by continuous feeding
      with a carcinogenic diet containing 2-AAF. We used two different strategies to
      genetically label hepatic cells: (a) labeling of proliferating cells in rats fed
      2-AAF by injecting recombinant retroviral vectors containing the beta
      galactosidase gene either in a peripheral vein or in the common bile duct at the
      peak of oval cell proliferation and (b) prelabeling of hepatocytes by
      intravenously injecting recombinant vectors 1 day after partial hepatectomy and 1
      week before subsequent administration of 2-AAF. Using the first strategy,
      transgene expression occurred in both oval cells and hepatocytes. Using the
      second strategy, we could selectively label, and hence study the fate of,
      differentiated hepatocytes. In the latter case, we observed clusters of beta
      galactosidase-positive hepatocytes, some of them also expressing preneoplastic
      markers such as gamma-glutamyl transpeptidase as well as the placental form of
      glutathione-S-transferase. These results demonstrate that preneoplastic foci can
      originate from mature hepatocytes and are consistent with the hypothesis that
      dedifferentiation of mature hepatocytes may occur during the course of
      carcinogenic regimen.

PMID- 12065690
TI  - Chymase participates in chronic dermatitis by inducing eosinophil infiltration.
AB  - An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear
      caused a transient skin swelling, and the repetition of the challenge enlarged
      the contact dermatitis. The repeated challenge with DNFB also induced eosinophil
      infiltration on the application site. Administration of a chymase inhibitor
      significantly inhibited the ear swelling as well as eosinophil accumulation. An
      intradermal injection of human chymase to the mouse ear also elicited transient
      skin swelling and eosinophil infiltration, both of which were augmented in
      proportion to the number of injections. Human serum albumin and heat-inactivated
      chymase failed to induce such skin reactions, suggesting the participation of
      proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil
      migration in vitro in a concentration-dependent manner. Taken together, these
      observations suggest that mast cell chymase may contribute to development of the
      DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is
      therefore possible that chymase plays a role in pathogenesis of chronic
      dermatitis such as atopic dermatitis.

PMID- 12065691
TI  - Conversion of Amadori products of the Maillard reaction to N(epsilon)
      (carboxymethyl)lysine by short-term heating: possible detection of artifacts by
      immunohistochemistry.
AB  - Accumulation of advanced glycation end products (AGE) of the Maillard reaction
      increases by aging and in age-enhanced diseases such as atherosclerosis and
      diabetic complications. Immunohistochemical analysis has been used to demonstrate
      AGE in vivo. In immunochemistry, the heat-induced epitope retrieval technique is
      extensively used with formalin-fixed, paraffin-embedded tissue sections. Here we
      examined whether AGE could be formed artificially through the heating process.
      Normal rat skin and liver samples were divided into two groups, one rapidly
      frozen, the other formalin-fixed, paraffin-embedded and submitted to heat-induced
      epitope retrieval treatment. In heat-treated sections, the cytoplasm of rat
      epidermal cells and hepatocytes were strongly stained by monoclonal antibody
      against N(epsilon)-(carboxymethyl)lysine (CML), while the staining was negligible
      in either frozen sections or in paraffin-embedded but heat-untreated sections. To
      clarify the mechanism, we conducted heat treatment to glycated human serum
      albumin (HSA), a model Amadori protein, and generation of CML was determined by
      immunochemical and HPLC analysis. CML was generated from glycated HSA by heat
      treatment (above 80 degrees C) and increased in a time-dependent manner. In
      contrast, generation of CML from glycated HSA was significantly inhibited in the
      presence of NaBH4, a reducing agent, diethylenetriamine pentaacetic acid, a
      chelator of transition metal ion, or aminoguanidine, a trapping reagent for alpha
      oxoaldehydes. Furthermore, heat-induced CML formation in rat liver samples
      determined by HPLC was markedly reduced by pretreatment with NaBH4. Reactive
      intermediates such as glucosone, 3-deoxyglucosone, methylglyoxal, and glyoxal
      were formed upon heat treatment of glycated HSA at 100 degrees C, indicating that
      these aldehydes generated from Amadori products by oxidative cleavage can
      contribute to further CML formation. CML generated by heating, directly from
      Amadori products or via these aldehydes, might serve as an artifact upon
      immunohistochemistry.

PMID- 12065692
TI  - A novel method for in vitro production of human glial-like cells from
      neurosurgical resection tissue.

PMID- 12065693
TI  - Molecular mechanisms for heterologous sensitization of adenylate cyclase.
AB  - The nine membrane-bound isoforms of the enzyme adenylate cyclase (EC 4.6.1.1) are
      highly regulated by neurotransmitters and drugs acting through G protein-coupled
      receptors to modulate intracellular cAMP levels. In general, acute activation of
      Galpha(s)-coupled receptors stimulates cAMP accumulation, whereas acute
      activation of Galpha(i/o)-coupled receptors typically inhibits cAMP accumulation.
      It is also well established that persistent activation of G-protein coupled
      receptors will alter subsequent drug-modulated cAMP accumulation. These
      alterations are thought to represent cellular adaptive responses following
      prolonged receptor activation. One phenomenon commonly observed, heterologous
      sensitization of adenylate cyclase, is characterized by an enhanced
      responsiveness to drug-stimulated cAMP accumulation following persistent
      activation of Galpha(i/o)-coupled receptors. Heterologous sensitization of
      adenylate cyclase was originally proposed to explain tolerance and withdrawal
      following chronic opiate administration and may be a mechanism by which cells
      adapt to prolonged activation of inhibitory receptors. Such an adaptive mechanism
      has been suggested to play a role in the processes of addiction to and withdrawal
      from many drugs of abuse and in psychiatric disorders including schizophrenia and
      depression. Although the precise mechanisms remain unknown, research over the
      last decade has led to advances toward understanding the molecular events
      associated with heterologous sensitization of recombinant and endogenous
      adenylate cyclases in cellular models. These events include the pertussis toxin
      sensitive events that are associated with the development of heterologous
      sensitization and the more recently identified Galpha(s)-dependent events that
      are involved in the expression of heterologous sensitization.

PMID- 12065694
TI  - Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent
      pathways.
AB  - The chemotherapeutic cisplatin causes renal dysfunction and renal proximal
      tubular cell (RPTC) apoptosis. The goal of these studies was to examine the role
      of p53, caspase 3, 8, and 9, and mitochondria in the signaling of cisplatin
      induced apoptosis. Cisplatin (50 microM) produced time-dependent apoptosis in
      RPTCs, causing cell shrinkage, a 50-fold increase in caspase 3 activity, a 4-fold
      increase in phosphatidylserine externalization, and 5- and 15-fold increases in
      chromatin condensation and DNA hypoploidy, respectively. Mitochondrial membrane
      potential and ATP levels did not change at any time during cisplatin exposure.
      Caspase 8 and 9 activities also did not increase during treatment. Cisplatin
      increased nuclear p53 expression 4 h after treatment, preceding both caspase 3
      activation and chromatin condensation. Treatment with the p53 inhibitor alpha-2
      (2-imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone (PFT) before
      cisplatin exposure inhibited p53 nuclear expression at 4, 8, and 12 h and
      inhibited phosphatidylserine externalization and caspase 3 activation at 12 h.
      Neither DEVD-fmk nor ZVAD-fmk inhibited cisplatin-induced p53 nuclear expression.
      Both DEVD-fmk and ZVAD-fmk completely inhibited caspase 3 activity but, like PFT,
      partially inhibited cisplatin-induced chromatin condensation, annexin V labeling,
      and DNA hypoploidy after 24 h. These data demonstrate that at least 50% of
      cisplatin-induced apoptosis in RPTC is mediated by p53 and that p53 activates
      caspase 3 independently of either caspase 9 or 8 or mitochondrial dysfunction.
      Furthermore, 50% of cisplatin-induced RPTC apoptosis is independent of p53 and
      caspases 3, 8, and 9.

PMID- 12065695
TI  - Nonsteroidal anti-inflammatory drugs induce apoptosis in association with
      activation of peroxisome proliferator-activated receptor gamma in rheumatoid
      synovial cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce
      apoptosis in a variety of cell lines. In this study, we examined the effect of
      NSAIDs on the growth and apoptosis of synovial cells from patients with
      rheumatoid arthritis and analyzed the activation of peroxisome proliferator
      activated receptor gamma (PPARgamma) as a possible mechanism of action of NSAIDs.
      Cell proliferation and viability were assessed from 5-bromo-2'-deoxyuridine
      incorporation and by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3
      benzene disulfonate (WST-1) assay, respectively. The apoptosis of synovial cells
      was identified by DNA fragmentation assay and terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay. Indometacin, diclofenac,
      oxaprozin, and zaltoprofen reduced cell proliferation and induced apoptotic cell
      death in synovial cells, whereas ketoprofen and acetaminophen did not. N-[2
      (cyclohexyloxyl)-4-nitrophenyl]-methanesulfonamide (NS-398), a selective
      cyclooxygenase-2 inhibitor, also inhibited cell proliferation, whereas it did not
      cause apoptosis. Rheumatoid synovial cells expressed PPARgamma mRNA, and the
      PPARgamma ligands 15-deoxy-Delta(12,14)-prostaglandin J(2) and troglitazone
      reduced the proliferation and induced apoptosis in synovial cells. Luciferase
      reporter assay demonstrated that not only PPARgamma ligands but also NSAIDs,
      which could induce apoptosis, increased the activation of PPARgamma in synovial
      cells. Furthermore, the ability of NSAIDs and PPARgamma ligands to stimulate the
      activation of PPARgamma correlated with their ability to decrease cell
      viability(r = 0.92, p < 0.01) and ability to induce DNA fragmentation (r = 0.97,
      p < 0.001) in synovial cells. These results suggest that PPARgamma is an
      attractive target for induction of apoptosis in rheumatoid synovial cells and
      that the activation of the PPARgamma pathway is associated with the apoptotic
      action of NSAIDs.

PMID- 12065696
TI  - Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells
      exposed to methylcyclopentadienyl manganese tricarbonyl.
AB  - Methylcyclopentadienyl manganese tricarbonyl (MMT), an organic manganese
      containing gasoline additive, was investigated to determine whether MMT
      potentially causes dopaminergic neurotoxic effects. MMT is acutely cytotoxic and
      dopamine-producing cells (PC-12) seemed to be more susceptible to cytotoxic
      effects than nondopaminergic cells (striatal gamma-aminobutyric acidergic and
      cerebellar granule cells). MMT also potently depleted dopamine apparently by
      cytoplasmic vesicular release to the cytosol, a neurochemical change resembling
      other dopaminergic neurotoxicants. Generation of reactive oxygen species (ROS),
      an early effect in toxicant-induced apoptosis, occurred within 15 min of MMT
      exposure. MMT caused a loss of mitochondrial transmembrane potential (DeltaPsim),
      a likely source of ROS generation. The ROS signal further activated caspase-3, an
      important effector caspase, which could be inhibited by antioxidants (Trolox or N
      acetyl cysteine). Predepletion of dopamine by using alpha-methyl-p-tyrosine
      (tyrosine hydroxylase inhibitor) treatment partially prevented caspase-3
      activation, denoting a significant dopamine and/or dopamine by-product
      contribution to initiation of apoptosis. Genomic DNA fragmentation, a terminal
      hallmark of apoptosis, was induced concentration dependently by MMT but
      completely prevented by pretreatment with Trolox, deprenyl (monoamine oxidase-B
      inhibitor), and alpha-methyl-p-tyrosine. A final set of critical experiments was
      performed to verify the pharmacological studies using a stable Bcl-2
      overexpressing PC-12 cell line. Bcl-2-overexpressing cells were significantly
      refractory to MMT-induced ROS generation, caspase-3 activation, and loss of
      DeltaPsim and were completely resistant to MMT-induced DNA fragmentation. Taken
      together, the results presented herein demonstrate that oxidative stress plays an
      important role in mitochondrial-mediated apoptotic cell death in cultured
      dopamine-producing cells after exposure to MMT.

PMID- 12065697
TI  - Alcohol activates activator protein-1 and mitogen-activated protein kinases in
      rat pancreatic stellate cells.
AB  - Alcohol is a major cause of both acute and chronic pancreatitis. Activated
      pancreatic stellate cells (PSCs) have recently been implicated in the
      pathogenesis of pancreatic inflammation and fibrosis. Herein, we examined the
      effect of ethanol and acetaldehyde on the activation of transcription factors and
      mitogen-activated protein (MAP) kinases in PSCs. PSCs were isolated from rat
      pancreas tissue and used in their culture-activated, myofibroblast-like
      phenotype. PSCs were treated with ethanol and acetaldehyde at clinically relevant
      concentrations (50 mM and 200 microM, respectively). Ethanol and acetaldehyde
      activated activator protein-1 but not nuclear factor-kappaB. In addition, they
      activated three classes of MAP kinases: extracellular signal-regulated kinase
      1/2, c-Jun N-terminal kinase/stress-activated protein kinase, and p38 MAP kinase.
      Ethanol- and acetaldehyde-induced activation of activator protein-1 and MAP
      kinases was blocked by the antioxidant N-acetyl-cysteine, suggesting a role of
      oxidative stress in the signal transduction. Ethanol and acetaldehyde induced
      alpha1(I) procollagen gene expression but did not induce intercellular adhesion
      molecule-1 and monocyte chemoattractant protein-1. The acetaldehyde-induced
      increase of alpha1(I) procollagen gene expression was inhibited by the p38 MAP
      kinase inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)imidazole (SB203580) but not by the MAP kinase inhibitor 2'-amino-3'
      methoxyflavone (PD98059). Specific activation of these signal transduction
      pathways may play a role in the pathogenesis of alcohol-induced pancreatic
      injury.

PMID- 12065698
TI  - Effect of albumin and cytosol on enzyme kinetics of tolbutamide hydroxylation and
      on inhibition of CYP2C9 by gemfibrozil in human liver microsomes.
AB  - The effect of human serum albumin (Hsa) and human liver cytosol (Hlc) on the in
      vitro enzyme kinetics of the formation of hydroxytolbutamide (CYP2C9 marker
      reaction) and the inhibitory effect of gemfibrozil on tolbutamide hydroxylation
      were examined using human liver microsomes. The addition of Hsa greatly decreased
      the unbound concentrations of tolbutamide and gemfibrozil in the incubation
      medium, whereas Hlc only slightly decreased them. The unbound K(m) value for
      tolbutamide hydroxylation was 123 microM without Hsa and Hlc, and 73, 88, and 64
      microM in the presence of Hsa (5 mg/ml), Hlc (0.5 mg/ml), and Hsa plus Hlc,
      respectively. The predicted in vivo hepatic clearance (CL(h)) of tolbutamide
      based on enzyme kinetics without Hsa and Hlc (0.06 ml/min/kg) was 40% of its in
      vivo clearance (0.15 ml/min/kg) based on published data. Addition of 5 mg/ml Hsa
      and 0.5 mg/ml Hlc to the incubation medium distinctly improved the prediction,
      with the coaddition of Hsa and Hlc yielding the most accurate value (0.14
      ml/min/kg). The K(i) (6 microM) of gemfibrozil for CYP2C9, calculated using total
      drug concentrations, was increased by Hlc (8 microM), Hsa (40 microM), or both
      (72 microM). However, when the unbound substrate and inhibitor concentrations
      were considered, the K(i) (6 microM without Hsa and Hlc) was not markedly altered
      by Hsa (4 microM), Hlc (8 microM), or both Hsa and Hlc (9 microM). The present
      findings suggest that the addition of Hsa and Hlc to microsomal incubation media
      may yield enzyme kinetic estimates more comparable with in vivo results.

PMID- 12065699
TI  - Modulation of blood-brain barrier dysfunction and neurological deficits during
      acute experimental allergic encephalomyelitis by the N-methyl-D-aspartate
      receptor antagonist memantine.
AB  - Previous studies by us have strongly indicated a role for the N-methyl-D
      aspartate (NMDA) receptor in the pathogenesis of experimental allergic
      encephalomyelitis (EAE) and, moreover, the loss of blood-brain barrier (BBB)
      integrity implicit in the disease. The current investigation has used the NMDA
      receptor antagonist memantine to modify the neurological course of EAE and, in
      particular, prevent BBB breakdown. Memantine was administered orally either
      semiprophylactically, from day 7 postinoculation (PI), or therapeutically, 10 to
      11 days PI. Semiprophylactic administration of drug at 60 mg/kg b.wt.
      significantly restored BBB integrity, reduced symptoms, and limited inflammatory
      lesions (p < 0.05), when assessed 12 days PI. Higher concentrations of memantine
      did not notably advance disease improvements observed at 60 mg/kg b.wt., and 40
      mg/kg b.wt. doses only reduced histological scores (p < 0.05). Therapeutic
      application of memantine was found to be as effective as semiprophylactic dosing.
      Administration of drug at 60 mg/kg b.wt. was demonstrated as the optimum dose,
      significantly reducing disease, BBB permeability, and lesions (p < 0.01).
      Extended studies revealed that, after cessation of memantine treatment using
      either dosing regime, any subsequent appearance of disease was suppressed in
      severity and duration. We have provided further strong evidence in support of a
      role for the NMDA receptor in the development of EAE and, in particular, the loss
      of BBB function and recruitment of inflammatory cells. Moreover, memantine is
      therapeutically efficacious, suggesting the NMDA receptor as a viable
      pharmacological target for future treatment of human neurological conditions such
      as multiple sclerosis.

PMID- 12065700
TI  - Biochemistry and pharmacology of epitope-tagged alpha(1)-adrenergic receptor
      subtypes.
AB  - Human alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenergic receptors were tagged at
      their amino termini with FLAG epitopes and stably expressed in human embryonic
      kidney (HEK)293 cells. Tagged receptors demonstrated a wild-type pharmacology and
      mobilization of intracellular Ca(2+). After solubilization and
      immunoprecipitation, monomers, dimers, and trimers of each subtype were apparent
      on Western blots. Further denaturation with 6 M urea reduced most oligomers to
      monomers. Deglycosylation reduced the molecular size of alpha(1A)-, and to a
      lesser extent alpha(1B)- and alpha(1D)-adrenergic receptors. Radioligand binding
      site density was highest for alpha(1A)- and much lower for alpha(1B)- and
      alpha(1D)-adrenergic receptors, but did not correlate with protein expression.
      Commercial anti-alpha(1)-adrenergic receptor antibodies did not recognize the
      tagged receptors in Western blots of cell lysates, and substantial cross
      reactivity was still observed after solubilization and immunoprecipitation.
      Surprisingly, only receptor monomers were apparent after photoaffinity labeling
      with (125)I-arylazidoprazosin, and the intensity of photoaffinity-labeling
      correlated with the density of radioligand binding sites. We conclude that
      epitope-tagged alpha(1)-adrenergic receptors exist as both monomers and oligomers
      in HEK293 cells, but there is substantial discrepancy between protein and binding
      site expression. Because only monomers are detected by photoaffinity labeling,
      dimers and trimers observed on Western blots may be pharmacologically inactive.

PMID- 12065701
TI  - Endothelium-independent vasodilator effects of the flavonoid quercetin and its
      methylated metabolites in rat conductance and resistance arteries.
AB  - The flavonoid quercetin is metabolized into isorhamnetin, tamarixetin, and
      kaempferol, the vascular effects of which are unknown. In the present study, the
      effects of quercetin and its metabolites were analyzed on isometric tension in
      isolated rat thoracic and abdominal aorta, in isolated intact and beta-escin
      permeabilized iliac arteries, and on perfusion pressure in the isolated
      mesenteric resistance vascular bed. In noradrenaline-precontracted vessels, the
      four flavonoids produced a vasodilator effect, which was inversely correlated
      with the diameter of the vessel studied; i.e., quercetin, isorhamnetin,
      tamarixetin, and kaempferol were 5-, 25-, 4-, and 6-fold, respectively, more
      potent in the resistance mesenteric bed (-log IC(50) = 5.35 +/- 0.15, 5.89 +/-
      0.11, 5.34 +/- 0.10, and 5.66 +/- 0.06, respectively) than in the thoracic aorta
      (-log IC(50) = 4.68 +/- 0.08, 4.61 +/- 0.08, 4.73 +/- 0.11, and 4.81 +/- 0.13,
      respectively; n = 4-6). The vasodilator responses of quercetin and isorhamnetin
      were not significantly modified after removal of the endothelium in the thoracic
      aorta or in the mesenteric bed. Furthermore, the guanylate cyclase inhibitor ODQ
      (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10(-6) M), the adenylate cyclase
      inhibitor SQ22536 [9-(tetrahydro-2-furanyl)-9H-purin-6-amine; 10(-6) M], KCl (40
      mM), or ouabain (10(-3) M) had no effect on isorhamnetin-induced vasodilation in
      the mesenteric bed. In permeabilized iliac arteries stimulated with Ca(2+) (pCa
      of 5.9), isorhamnetin was also significantly more potent (-log IC(50) = 5.27 +/-
      0.15) than quercetin (-log IC(50) = 4.56 +/- 0.15). In conclusion, quercetin and
      its metabolites showed vasodilator effects with selectivity toward the resistance
      vessels. These effects are not due to or modulated by endothelial factors and are
      unrelated to changes in cytosolic Ca(2+).

PMID- 12065702
TI  - Pharmacological activity of fatty acid amides is regulated, but not mediated, by
      fatty acid amide hydrolase in vivo.
AB  - Fatty acid amides (FAAs) represent a class of neuromodulatory lipids that
      includes the endocannabinoid anandamide and the sleep-inducing substance
      oleamide. Both anandamide and oleamide produce behavioral effects indicative of
      cannabinoid activity, but only anandamide binds the cannabinoid (CB1) receptor in
      vitro. Accordingly, oleamide has been proposed to induce its behavioral effects
      by serving as a competitive substrate for the brain enzyme fatty acid amide
      hydrolase (FAAH) and inhibiting the degradation of endogenous anandamide. To test
      the role that FAAH plays as a mediator of oleamide activity in vivo, we have
      compared the behavioral effects of this FAA in FAAH(+/+) and (-/-) mice. In both
      genotypes, oleamide produced hypomotility, hypothermia, and ptosis, all of which
      were enhanced in FAAH(-/-) mice, were unaffected by the CB1 antagonist N
      (piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-di-chlorophenyl)-4-methyl-1H-pyrazole
      3-carboxamide hydrochloride (SR141716A) and occurred in CB1(-/-) mice.
      Additionally, oleamide displayed negligible binding to the CB1 receptor in brain
      extracts from either FAAH(+/+) or (-/-) mice. In contrast, anandamide exhibited a
      15-fold increase in apparent affinity for the CB1 receptor in brains from FAAH(-/
      ) mice, consistent with its pronounced CB1-dependent behavioral effects in these
      animals. Contrary to both oleamide and anandamide, monoacylglycerol lipids
      exhibited equivalent hydrolytic stability and pharmacological activity in
      FAAH(+/+) and (-/-) mice. Collectively, these results indicate that FAAH is a key
      regulator, but not mediator of FAA activity in vivo. More generally, these
      findings suggest that FAAs represent a family of signaling lipids that, despite
      sharing similar chemical structures and a common pathway for catabolism, produce
      their behavioral effects through distinct receptor systems in vivo.

PMID- 12065703
TI  - Bisphenol A inhibits Cl(-) secretion by inhibition of basolateral K+ conductance
      in human airway epithelial cells.
AB  - There has been growing concern about the potential threat of hormone-disrupting
      chemicals like bisphenol A to various aspects of animal and human health. We
      studied the effects of bisphenol A on the Cl(-) secretion in human airway
      epithelial Calu-3 cells. Pretreatment with bisphenol A (IC(50) = 60 microM, for
      30 min) prevented isoproterenol (10 nM)-generated short-circuit current (I(sc))
      more potently than 17beta-estradiol or tamoxifen (IC(50) = 1 mM). 5'-Nitro-2-(3
      phenylpropylamino) benzoate-sensitive apical conductance potentiated by
      isoproterenol was not affected by the pretreatment with either of these
      estrogenic compounds. The effects of bisphenol A were simulated in I(sc)
      responses to forskolin (10 microM) and 8-bromo-cAMP (1 mM). Nystatin
      permeabilization of Calu-3 monolayers revealed that bisphenol A attenuated 8
      bromo-cAMP-induced basolateral K+ current, which is sensitive to clotrimazole (30
      microM) and insensitive to charybdotoxin (100 nM), without affecting the apical
      Cl(-) current. Bisphenol A, but neither 17beta-estradiol nor tamoxifen,
      interrupted the charybdotoxin-sensitive component of I(sc) stimulated by 1-ethyl
      2-benzimidazolinone (1-EBIO; 500 microM). The inhibitory effects of bisphenol A
      on these Cl(-) secretory stimuli were remarkable when applied to the apical
      rather than the basolateral membrane. Alternatively, long-term incubation of
      bisphenol A (1 microM; 12-72 h) had no discernible effect on isoproterenol- and 1
      EBIO-induced Cl(-) secretion. These findings indicate that short-term exposure to
      bisphenol A attenuates transepithelial Cl(-) secretion through inhibition of both
      cAMP- and Ca(2+)-activated K+ channels on the basolateral membrane, interacting
      from the cytosolic surface in Calu-3 cells.

PMID- 12065704
TI  - Cytoprotective properties of novel nonpeptide calpain inhibitors in renal cells.
AB  - Calpains are cytosolic, Ca(2+)-activated, neutral cysteine proteases. Rabbit
      renal proximal tubule (RPT) cells express both mu- and m-calpain. Although
      multiple calpain inhibitors protect against RPT cell death, most calpain
      inhibitors lack specificity, membrane permeability, and/or potency. A group of
      novel catalytic site-directed calpain inhibitors, including chloroacetic acid N'
      [6,7-dichloro-4-(4-methoxy-phenyl)-3-oxo-3,4-dihydroquinoxalin-2-yl]hydrazide
      (SJA7019) and chloroacetic acid N'-(6,7-dichloro-4-phenyl-3-oxo-3,4
      dihydroquinoxalin-2-yl) hydrazide (SJA7029), were identified to be potent calpain
      inhibitors in vitro. The goals of this study were to determine the action of
      these two compounds on 1) RPT calpain activity using fluorescein isothiocyanate
      casein zymography, 2) antimycin A-induced RPT extracellular (45)Ca(2+) influx and
      cell death, and 3) hypoxia/reoxygenation-induced RPT cellular dysfunction and
      death. The results showed that the SJA compounds inhibited RPT mu- and m-calpain
      with equal potency (approximate IC(50), 30 microM) and efficacy, and blocked
      antimycin A-induced extracellular Ca(2+) influx and cell death. In addition,
      SJA7029 blocked cell death and allowed the recovery of mitochondrial function and
      active Na(+) transport in RPTs subjected to hypoxia/reoxygenation. In summary,
      the SJA compounds 1) were more potent inhibitors of calpains than catalytic site
      directed peptide inhibitors in this model, 2) prevented extracellular Ca(2+)
      influx during the late phase of cell death, and 3) are true cytoprotectants and
      allow recovery of RPT cellular functions after injury.

PMID- 12065705
TI  - Alpha4beta2 nicotinic acetylcholine receptor activation ameliorates impairment of
      spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats,
      an animal model of attention deficit hyperactivity disorder.
AB  - The objective of the present study was to elucidate the role of nicotine in
      impairment of spontaneous alternation behavior of juvenile stroke-prone
      spontaneously hypertensive rats (SHRSP), an animal model of attention deficit
      hyperactivity disorder (ADHD). Spontaneous alternation behavior assessed by a Y
      maze task was significantly lower, and total arm entries were significantly
      higher in SHRSP than in genetic control Wistar-Kyoto rats. Nicotine (0.1-1 mg/kg,
      s.c.) dose dependently improved the spontaneous alternation deficit without
      affecting total arm entries in SHRSP. Nicotine-induced (1 mg/kg, s.c.)
      improvement was significantly abolished by the centrally acting nicotinic
      acetylcholine receptor (nAChR) antagonist mecamylamine (1 mg/kg, i.p.), but not
      by peripherally acting hexamethonium (5 mg/kg, i.p.), suggesting that nicotine
      induced improvement is mediated via central nAChR. The alpha4beta2 nAChR
      antagonist dihydro-beta-erythroidine (3-10 mg/kg, i.p.) dose dependently
      counteracted nicotine-induced improvement of spontaneous alternation in SHRSP,
      whereas the alpha7 nAChR antagonist methyllycaconitine (3-10 mg/kg, i.p.) did
      not. In addition, the alpha4beta2 nAChR agonist RJR-2403 (N-methyl-4-(3
      pyridinyl)-3-butene-1-amine; 1-10 mg/kg, s.c.) dose dependently and significantly
      improved the spontaneous alternation deficit. These findings revealed that
      nicotine improved spontaneous alternation behavior in SHRSP via the activation of
      alpha4beta2, but not alpha7, nAChR. Thus, the alpha4beta2 nAChR mechanism might
      be responsible for the spontaneous alternation deficit in juvenile SHRSP, an
      animal model of ADHD. This evidence indicates the possibility that selective
      alpha4beta2 nAChR agonists might be useful for treating attentional dysfunction
      in ADHD.

PMID- 12065706
TI  - Clocinnamox distinguishes opioid agonists according to relative efficacy in
      normal and morphine-treated rats trained to discriminate morphine.
AB  - High doses of insurmountable antagonists or frequent administration of high doses
      of agonists are required to alter the potency of opioid agonists to produce
      discriminative stimuli. In the present study, insurmountable antagonism and
      repeated agonist treatment were combined to remove or disable a large enough
      proportion of mu-opioid receptors to alter the potency or maximal effect for four
      agonists in male Sprague-Dawley rats trained to discriminate 3.2 mg/kg morphine
      from saline under a fixed-ratio 15 schedule of food reinforcement. All agonists
      produced 88 to 100% morphine responding and were differentially sensitive to
      clocinnamox antagonism (fentanyl < morphine < or = buprenorphine = nalbuphine).
      Repeated treatment with 20 mg/kg per day morphine for 6 days decreased by 2- to 3
      fold the potency of fentanyl, morphine, and buprenorphine to produce morphine
      responding. After morphine treatment, 3.2 mg/kg clocinnamox produced a 7-fold
      further decrease in morphine potency. Clocinnamox (10 mg/kg) produced a 7- and 12
      fold further decrease in morphine and fentanyl potency, respectively, a reduction
      in the slope of the morphine dose-response curve, and a suppression of the
      maximal morphine responding for buprenorphine. Repeated treatment with 10 mg/kg
      per day morphine for 6 days failed to alter the potency of nalbuphine to produce
      morphine responding. In these morphine-treated rats, doses of 3.2 or 10 mg/kg
      clocinnamox suppressed the maximal morphine responding. Taken together, these
      data indicate that combined insurmountable antagonist and repeated agonist
      treatment produce additive effects at mu-opioid receptors to diminish
      discriminative stimulus effects in a manner predicted by the relative efficacy of
      opioid agonists.

PMID- 12065707
TI  - A novel cAMP-stimulated pathway in protein phosphatase 2A activation.
AB  - Elevated cAMP in NRK-52E and L6 cells causes a marked reduction in the
      phosphorylation of numerous phosphoproteins, as detected initially with
      phosphoserine-specific antibodies. Here, we show that elevation of cAMP in NRK
      cells by forskolin/3-isobutyl-1-methylxanthine (IBMX) treatment decreased
      phosphorylation of substrates for different protein kinases, pointing to a common
      protein phosphatase as a target for cAMP-dependent regulation. Forskolin/IBMX
      treatment completely dephosphorylated a selective protein phosphatase 2A (PP2A)
      substrate, elongation factor-2 (EF-2), at its Ca(2+) calmodulin-dependent kinase
      site, and decreased phosphorylation of substrates for cyclin-dependent kinases,
      including retinoblastoma (Rb) protein. As reported before, forskolin/IBMX also
      decreased phosphorylation of a protein kinase C substrate, the Na,K-ATPase. The
      cAMP-stimulated dephosphorylation was blocked by the protein phosphatases 1 (PP1)
      and PP2A inhibitor okadaic acid at concentrations selective for PP2A but was not
      blocked by tautomycin at concentrations selective for PP1. The data implicate
      PP2A as a cAMP-activated phosphatase. Contrary to expectation, we found evidence
      that cAMP-dependent activation of PP2A did not depend on protein kinase A (PKA).
      Pretreatment of cells with the PKA inhibitor H89 abolished PKA activity measured
      in cell extracts and significantly decreased cAMP-activated phosphorylation of a
      known PKA substrate, ARPP-19, in cells, but failed to block the cAMP-stimulated
      dephosphorylation of EF-2, Rb, and other proteins. This novel pathway of PP2A
      activation, acting on the time scale of minutes, represents yet another example
      of a cAMP-mediated, PKA-independent signaling mechanism. Because PP2A is active
      toward a variety of endogenous substrates, cAMP-stimulated dephosphorylation may
      have complicated the interpretation of many prior studies.

PMID- 12065708
TI  - A single dose of monoclonal anti-phencyclidine IgG offers long-term reductions in
      phencyclidine behavioral effects in rats.
AB  - These studies tested the hypothesis that a single dose of high-affinity anti
      phencyclidine monoclonal antibody (anti-PCP mAb) provides long-term protection
      against behavioral effects of repeated PCP administration in rats. Rats were
      treated with saline, nonspecific bovine IgG (NS-IgG), or anti-PCP mAb (1.0 g/kg).
      The next morning, the rats were challenged with escalating i.v. doses of PCP
      (0.32, 0.56, and 1.0 mg/kg) at 90-min intervals. This regimen was repeated every
      3 days for 2 weeks. In the saline and NS-IgG control groups, PCP yielded
      reproducible and linear dose-dependent effects that remained constant during the
      experiment. In contrast, the anti-PCP mAb treatment blocked PCP effects on day 1,
      and sustained significant (P < 0.05) reductions in drug effects for the entire 2
      week experiment. Brain PCP concentrations (determined at study termination) were
      reduced by ~55%, whereas serum concentrations were increased over 4000% compared
      with controls. Thus, a single dose of antibody medication provided long-term
      reductions in drug effects and brain concentrations, beyond the expected capacity
      of the drug-antibody interaction. These data challenge current concepts about in
      vivo dose dependence and unimolecular interaction between antibody binding sites
      and small molecules and establish that neuroprotection by mAbs may have an unique
      mechanism of action.

PMID- 12065710
TI  - Inhibition of inducible nitric-oxide synthase expression by silymarin in
      lipopolysaccharide-stimulated macrophages.
AB  - Silymarin, a polyphenolic flavonoid antioxidant, is known to have anti
      inflammatory, hepatoprotective, and anticarcinogenic effects. In the present
      study, we report the inhibitory effect of silymarin on nitric oxide production
      and inducible nitric-oxide synthase (iNOS) gene expression in macrophages. In
      vivo administration of silymarin attenuated nitric oxide production by peritoneal
      macrophages in lipopolysaccharide (LPS)-treated mice. Silymarin also dose
      dependently suppressed the LPS-induced production of nitric oxide in isolated
      mouse peritoneal macrophages and RAW 264.7, a murine macrophage-like cell line.
      Moreover, iNOS mRNA and its protein expression were completely abrogated by
      silymarin in LPS-stimulated RAW 264.7 cells. To further investigate the mechanism
      responsible for the inhibition of iNOS gene expression by silymarin, we examined
      the effect of silymarin on LPS-induced nuclear factor-kappaB (NF-kappaB)/Rel
      activation, which regulates various genes involved in immune and inflammatory
      response. In RAW 264.7 cells, the LPS-induced DNA binding activity of NF
      kappaB/Rel was significantly inhibited by silymarin, and this effect was mediated
      through the inhibition of the degradation of inhibitory factor-kappaB. Silymarin
      also inhibited tumor necrosis factor-alpha-induced NF-kappaB/Rel activation,
      whereas okadaic acid-induced NF-kappaB/Rel activation was not affected. NF
      kappaB/Rel-dependent reporter gene expression was also suppressed by silymarin in
      LPS-stimulated RAW 264.7 cells. Further study showed that silymarin suppressed
      the production of reactive oxygen species generated by H(2)O(2) in RAW 264.7
      cells. Collectively, these results suggest that silymarin inhibits nitric oxide
      production and iNOS gene expression by inhibiting NF-kappaB/Rel activation.
      Furthermore, the radical-scavenging activity of silymarin may explain its
      inhibitory effect on NF-kappaB/Rel activation.

PMID- 12065709
TI  - Pharmacology of N-(3,5-dichloro-1-oxido-4-pyridinyl)-8-methoxy-2
      (trifluoromethyl)-5-quinoline carboxamide (SCH 351591), a novel, orally active
      phosphodiesterase 4 inhibitor.
AB  - N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline
      carboxamide (SCH 351591) has been identified as a potent (IC(50) = 58 nM) and
      highly selective type 4 phosphodiesterase (PDE4) inhibitor with oral bioactivity
      in several animal models of lung inflammation. N-(3,5-Dichloro-4-pyridinyl)-8
      methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 365351), the only
      significant in vivo metabolite, is also a potent and highly selective PDE4
      inhibitor (IC(50) = 20 nM). Both SCH 351591 and SCH 365351 inhibited cytokine
      production in human blood mononuclear cell preparations. Oral SCH 351591
      significantly attenuated allergen-induced eosinophilia and airway hyperreactivity
      in allergic guinea pigs at doses as low as 1 mg/kg. In this model, oral SCH
      365351 showed similar potency. When SCH 351591 was administered orally to
      allergic cynomolgus monkeys at 3 mg/kg, Ascaris suum-induced lung eosinophilia
      was blocked. Hyperventilation-induced bronchospasm in nonallergic guinea pigs, a
      model for exercise-induced asthma, was also suppressed significantly by oral SCH
      351591 at 0.3 mg/kg. Cilomilast (SB 207499; Ariflo), a PDE4 inhibitor currently
      being developed for asthma and chronic obstructive pulmonary disease (COPD), was
      10- to 30-fold less potent than SCH 351591 at inhibiting guinea pig lung
      eosinophilia and hyperventilation-induced bronchospasm. In a ferret model of
      emesis, maximum nonemetic oral doses of SCH 351591 and cilomilast were 5 and 1
      mg/kg, respectively. Comparison of plasma levels at these nonemetic doses in
      ferrets to those at doses inhibiting hyperventilation-induced bronchospasm in
      guinea pigs gave a therapeutic ratio of 16 for SCH 351591 and 4 for cilomilast.
      Thus, SCH 351591 exhibits a promising preclinical profile as a treatment for
      asthma and COPD.

PMID- 12065711
TI  - Pharmacological evidence supporting a role for central corticotropin-releasing
      factor(2) receptors in behavioral, but not endocrine, response to environmental
      stress.
AB  - Corticotropin-releasing factor (CRF) is one of the principle components of the
      stress response. The physiological effects of CRF are mediated by two receptor
      subtypes, CRF(1) and CRF(2). Recent data obtained with the selective CRF(2)
      antagonist antisauvagine-30 (ASV-30) has begun to suggest that both CRF receptor
      subtypes may play a role in stress-related behaviors. Exactly how these two
      receptor subtypes interact to modulate the behavioral and endocrine responses to
      stress is not clear, however. We have attempted to understand the role of the
      CRF(2) receptor in the behavioral and endocrine responses to stress by comparing
      the effects of ASV-30 with the mixed CRF(1)/CRF(2) receptor antagonist astressin.
      Centrally administered ASV-30 reduced anxiety-like behavior in BALB/c mice in
      three models of anxiety: marble burying [minimal effective dose (MED) = 3 nmol],
      open field (MED = 3 nmol), and elevated plus maze (MED = 0.1 nmol). ASV-30 did
      not change locomotor activity or the adrenocorticotropic hormone (ACTH) response
      to restraint stress. The potent mixed CRF(1)/CRF(2) antagonist astressin not only
      reduced anxiety-like behavior in all three models with equivalent potency but
      also blunted the ACTH response to restraint stress. Finally, the new selective
      CRF(2) receptor agonist urocortin-II produced a dose-dependent increase in
      anxiety-like behavior in the plus maze test. Therefore, our data suggest that the
      CRF(2) receptor plays a role in the behavioral, but not the hypothalamic
      pituitary-adrenal axis, response to stress.

PMID- 12065712
TI  - Alpha(4)beta(7)/alpha(4)beta(1) dual integrin antagonists block alpha(4)beta(7)
      dependent adhesion under shear flow.
AB  - The alpha(4) integrin, alpha(4)beta(7), plays an important role in recruiting
      circulating lymphocytes to the gastrointestinal tract, where its ligand mucosal
      addressin cell adhesion molecule-1 (MAdCAM-1) is preferentially expressed on high
      endothelial venules (HEVs). Dual antagonists of alpha(4)beta(1) and
      alpha(4)beta(7), N-(2,6-dichlorobenzoyl)-(L)-4-(2',6'-bis
      methoxyphenyl)phenylalanine (TR14035) and N-(N-[(3,5-dichlorobenzene)sulfonyl]-2
      (R)-methylpropyl)-(D)-phenylalanine (compound 1), were tested for their ability
      to block the binding of alpha(4)beta(7)-expressing cells to soluble ligand in
      suspension and under in vitro and in vivo shear flow. Compound 1 and TR14035
      blocked the binding of human alpha(4)beta(7) to an (125)I-MAdCAM-Ig fusion
      protein with IC(50) values of 2.93 and 0.75 nM, respectively. Both compounds
      inhibited binding of soluble ligands to alpha(4)beta(1) or alpha(4)beta(7) on
      cells of human or rodent origin with similar potency. Under shear flow in vitro,
      TR14035 and compound 1 blocked binding of human alpha(4)beta(7)-expressing RPMI
      8866 cells or murine mesenteric lymph node lymphocytes to MAdCAM-Ig with IC(50)
      values of 0.1 and 1 microM, respectively. Intravital microscopy was used to
      quantitate alpha(4)-dependent adhesion of fluorescent murine lymphocytes in
      Peyer's patch HEVs. When cells were prestimulated with 2 mM Mn(2+) to activate
      alpha(4)beta(7) binding to ligand, anti-alpha(4) monoclonal antibody (mAb) [10
      mg/kg (mpk) i.v.] blocked adhesion by 95%, and anti-beta(1) mAb did not block
      adhesion, demonstrating that this interaction was dependent on alpha(4)beta(7).
      TR14035 blocked adhesion to HEVs [ED(50) of 0.01-0.1 mpk i.v.], and compound 1
      blocked adhesion by 47% at 10 mpk i.v. Thus, alpha(4)beta(7)/alpha(4)beta(1)
      antagonists blocked alpha(4)beta(7)-dependent adhesion of lymphocytes to HEVs
      under both in vitro and in vivo shear flow.

PMID- 12065713
TI  - A novel N-methyl-D-aspartate receptor open channel blocker with in vivo
      neuroprotectant activity.
AB  - Excitotoxicity has been implicated in the etiology of ischemic stroke, chronic
      neurodegenerative disorders, and very recently, in glioma growth. Thus, the
      development of novel neuroprotectant molecules that reduce excitotoxic brain
      damage is vigorously pursued. We have used an ionic current block-based cellular
      assay to screen a synthetic combinatorial library of trimers of N-alkylglycines
      on the N-methyl-D-aspartate (NMDA) receptor, a well known molecular target
      involved in excitotoxicity. We report the identification of a family of N
      alkylglycines that selectively blocked the NMDA receptor. Notably, compound 3,3
      diphenylpropyl-N-glycinamide (referred to as N20C) inhibited NMDA receptor
      channel activity with micromolar affinity, fast on-off blockade kinetics, and
      strong voltage dependence. Molecule N20C did not act as a competitive glutamate
      or glycine antagonist. In contrast, saturation of the blocker binding site with
      N20C prevented dizolcipine (MK-801) blockade of the NMDA receptor, implying that
      both drugs bind to the same receptor site. The N-alkylglycine efficiently
      prevented in vitro excitotoxic neurodegeneration of cerebellar and hippocampal
      neurons in culture. Attenuation of neuronal glutamate/NMDA-induced Ca(2+)
      overload and subsequent modulation of the glutamate-nitric oxide-cGMP pathway
      seems to underlie N20C neuroprotection. Noteworthy, this molecule exhibited
      significant in vivo neuroprotectant activity against an acute, severe,
      excitotoxic insult. Taken together, these findings indicate that N-alkylglycine
      N20C is a novel, low molecular weight, moderate-affinity NMDA receptor open
      channel blocker with in vitro and in vivo neuroprotective activity, which, in due
      turn, may become a tolerated drug for the treatment of neurodegenerative diseases
      and cancer.

PMID- 12065714
TI  - The selective serotonin reuptake inhibitor citalopram induces the storage of
      serotonin in catecholaminergic terminals.
AB  - We investigated whether selective inhibition of serotonin (5-hydroxytryptamine; 5
      HT) transporter with citalopram leads to accumulation of 5-HT in
      catecholaminergic neurons. In the rabbit olfactory tubercle, citalopram (1-10
      microM) inhibited [(3)H]5-HT uptake; however, the maximal degree of inhibition
      achieved was 70%. Addition of nomifensine (1-10 microM) was required for complete
      inhibition of [(3)H]5-HT uptake. In slices labeled with 0.1 microM [(3)H]5-HT,
      cold 5-HT (0.03-1 microM) induced a large increase in the efflux (release) of
      stored [(3)H]5-HT, an effect blocked by coperfusion with 1 microM citalopram.
      Similar concentrations (0.03-1 microM) of norepinephrine (NE) or dopamine (DA)
      failed to release [(3)H]5-HT. When labeling with 0.1 microM [(3)H]5-HT was
      carried out in the presence of citalopram, 1) low concentrations of 5-HT failed
      to release [(3)H]5-HT; 2) DA and NE were more potent and effective in releasing
      [(3)H]5-HT than in control slices; 3) coperfusion of NE, DA, or 5-HT with
      citalopram enhanced the release of [(3)H]5-HT induced by the catecholamines but
      not by 5-HT; and 4) coperfusion of NE or DA with nomifensine antagonized NE- and
      DA-evoked [(3)H]5-HT release, with a greater effect on NE than on DA. These
      results suggest that in the rabbit olfactory tubercle, where there is coexistence
      of 5-HT, NE, and DA neurons, inhibition of the 5-HT transporter led to
      accumulation of 5-HT in catecholaminergic terminals. Thus, during treatment with
      selective serotonin uptake inhibitors (SSRIs), 5-HT may be stored in
      catecholaminergic neurons acting as a false neurotransmitter and/or affecting the
      disposition of DA and/or NE. Transmitter relocation may be involved in the
      antidepressant action of SSRIs.

PMID- 12065715
TI  - Therapeutic intervention in mice deficient for succinate semialdehyde
      dehydrogenase (gamma-hydroxybutyric aciduria).
AB  - Therapeutic intervention for human succinic semialdehyde dehydrogenase (SSADH)
      deficiency (gamma-hydroxybutyric aciduria) has been limited to vigabatrin (VGB).
      Pharmacologically, VGB should be highly effective due to 4-aminobutyrate
      transaminase (GABA-transaminase) inhibition, lowering succinic semialdehyde and,
      thereby, gamma-hydroxybutyric acid (GHB) levels. Unfortunately, clinical efficacy
      has been limited. Because GHB possesses a number of potential receptor
      interactions, we addressed the hypothesis that antagonism of these interactions
      in mice with SSADH deficiency could lead to the development of novel treatment
      strategies for human patients. SSADH-deficient mice have significantly elevated
      tissue GHB levels, are neurologically impaired, and die within 4 weeks
      postnatally. In the current report, we compared oral versus intraperitoneal
      administration of VGB, CGP 35348 [3-aminopropyl(diethoxymethyl)phosphinic acid, a
      GABA(B) receptor antagonist], and the nonprotein amino acid taurine in rescue of
      SSADH-deficient mice from early death. In addition, we assessed the efficacy of
      the specific GHB receptor antagonist NCS-382 (6,7,8,9-tetrahydro-5
      [H]benzocycloheptene-5-ol-6-ylideneacetic acid) using i.p. administration. All
      interventions led to significant lifespan extension (22-61%), with NCS-382 being
      most effective (50-61% survival). To explore the limited human clinical efficacy
      of VGB, we measured brain GHB and gamma-aminobutyric acid (GABA) levels in SSADH
      deficient mice receiving VGB. Whereas high-dose VGB led to the expected elevation
      of brain GABA, we found no parallel decrease in GHB levels. Our data indicate
      that, at a minimum, GHB and GABA(B) receptors are involved in the pathophysiology
      of SSADH deficiency. We conclude that taurine and NCS-382 may have therapeutic
      relevance in human SSADH deficiency and that the poor clinical efficacy of VGB in
      this disease may relate to an inability to decrease brain GHB concentrations.

PMID- 12065716
TI  - Profound spinal tolerance after repeated exposure to a highly selective mu-opioid
      peptide agonist: role of delta-opioid receptors.
AB  - Recent studies suggest that delta-opioid receptors play a role in the development
      of opioid tolerance and led us to hypothesize that highly selective mu-opioid
      agonists may produce less tolerance. H-2',6'-dimethyltyrosine-D-Arg-Phe-Lys-NH(2)
      ([Dmt(1)]DALDA) has extraordinary selectivity for mu-receptors
      (K(i)(delta)/K(i)(mu) > 14,000). Daily administration of [Dmt(1)]DALDA (5 times
      ED(50); s.c.) for 7 days increased ED(50) 3.6-fold from 0.16 to 0.58 micromol/kg.
      A higher dose of [Dmt(1)]DALDA (10 times ED(50), every 12 h) for 2.5 days
      resulted in a 11.7 times increase in the ED(50) (1.9 micromol/kg). Complete cross
      tolerance to morphine was observed, with a 3.4- and 15.1-fold shift in the
      morphine ED(50), respectively. We also compared the extent of spinal versus
      supraspinal tolerance after repeated s.c. [Dmt(1)]DALDA administration. Five
      doses of [Dmt(1)]DALDA (10 times ED(50), every 12 h) resulted in a 3.4 times
      shift in the i.c.v. ED(50) (15.4 versus 4.6 pmol/mouse) but a 44 times shift in
      the i.t. ED(50) (52.9 versus 1.2 pmol/mouse). Tolerance to [Dmt(1)]DALDA was
      associated with 30 to 35% reduction in [(3)H][Dmt(1)]DALDA binding in brain and
      spinal cord. Coadministration of [Dmt(1)]DALDA with delta-antagonist naltriben
      (NTB) reduced spinal tolerance by 50%. Even after spinal tolerance had been
      established, addition of a delta-antagonist (NTB or H-Tyr-TicPsi[CH(2)NH]Phe-Phe
      OH) significantly enhanced the potency of i.t. [Dmt(1)]DALDA 2- to 4-fold. These
      results suggest that agonist activation of delta-receptors is not necessary for
      the development of opioid tolerance; however, delta-receptors play a modulatory
      role in the maintenance of the tolerant state.

PMID- 12065718
TI  - Rapid inhibition of thyroxine-induced bone resorption in the rat by an orally
      active vitronectin receptor antagonist.
AB  - An excess of thyroid hormone results in increased bone turnover and loss of bone
      mass in humans. Exogenous administration of thyroid hormone to rats has served as
      a model of human hyperthyroidism in which antiresorptive therapies have been
      tested. We have further refined this model of thyroxine (T4)-induced turnover in
      the rat. Daily administration of T4 to aged rats for as short as 1 week resulted
      in elevated bone resorption determined by significantly higher urinary
      deoxypyridinoline (Dpd) compared with vehicle controls or animals receiving T4
      plus estradiol. Three weeks of daily administration of T4 led to significantly
      lower bone mineral density compared with untreated controls or animals receiving
      T4 plus estradiol. In a follow-up study, a depot formulation of T4 caused an
      increase in Dpd identical to that achieved with a bolus dose. SB-273005 [(4S)
      2,3,4,5-tetrahydro-8-[2-[6-(methylamino)-2-pyridinyl] ethoxy]-3-oxo-2-(2,2,2
      trifluoroethyl)-1H-2-benzazepine-4- acetic acid] a potent antagonist of the
      integrins alpha(v)beta(3) and alpha(v)beta(5), has been shown previously to
      inhibit bone resorption in cultures of human osteoclasts and to protect bone in
      ovariectomized rats. The effect of SB-273005 by oral administration was evaluated
      in this thyroxine-induced turnover model. Dose-dependent inhibition of resorption
      was seen with SB-273005 after 7 days of dosing using Dpd as a measure of bone
      resorption. In summary, it has been demonstrated that the antiresorptive activity
      of a vitronectin receptor antagonist can be measured after only 7 days of
      treatment in this refined rat model of thyroxine-induced bone turnover. These
      data suggest that SB-273005 may be useful for the treatment of metabolic bone
      diseases, including those resulting from hyperthyroidism.

PMID- 12065717
TI  - Methyllycaconitine is a potent antagonist of alpha-conotoxin-MII-sensitive
      presynaptic nicotinic acetylcholine receptors in rat striatum.
AB  - The plant alkaloid methyllycaconitine (MLA) is considered to be a selective
      antagonist of the alpha7 subtype of neuronal nicotinic acetylcholine receptor
      (nAChR). However, 50 nM MLA partially inhibited (by 16%) [(3)H]dopamine release
      from rat striatal synaptosomes stimulated with 10 microM nicotine. Other alpha7
      selective antagonists had no effect. Similarly, MLA (50 nM) inhibited
      [(3)H]dopamine release evoked by the partial agonist (2-chloro-5-pyridyl)-9
      azabicyclo[4.2.1]non-2-ene (UB-165) (0.2 microM) by 37%. In both cases,
      inhibition by MLA was surmountable with higher agonist concentrations, indicative
      of a competitive interaction. At least two subtypes of presynaptic nAChR can
      modulate dopamine release in the striatum, and these nAChR are distinguished by
      their differential sensitivity to alpha-conotoxin-MII (alpha-CTx-MII). MLA was
      not additive with a maximally effective concentration of alpha-CTx-MII (100 nM)
      in inhibiting [(3)H]dopamine release elicited by 10 microM nicotine or 0.2 microM
      UB-165, suggesting that both toxins act at the same site. This was confirmed in
      quantitative binding assays with (125)I-alpha-CTx-MII, which displayed saturable
      specific binding to rat striatum and nucleus accumbens with B(max) values of 9.8
      and 16.5 fmol/mg of protein, and K(d) values of 0.63 and 0.83 nM, respectively.
      MLA fully inhibited (125)I-alpha-CTx-MII binding to striatum and nucleus
      accumbens with a K(i) value of 33 nM, consistent with the potency observed in the
      functional assays. We speculate that MLA and alpha-CTx-MII interact with a
      presynaptic nAChR of subunit composition alpha3/alpha6beta2beta3* on dopamine
      neurons. The use of MLA as an alpha7-selective antagonist should be exercised
      with caution, especially in studies of nAChR in basal ganglia.

PMID- 12065719
TI  - Differential effects of short and prolonged exposure to carvedilol on voltage
      dependent Na(+) channels in cultured bovine adrenal medullary cells.
AB  - We examined the effects of short and prolonged exposure to carvedilol, an
      antihypertensive and beta-adrenoceptor blocking drug, on voltage-dependent Na(+)
      channels in cultured bovine adrenal medullary cells. Carvedilol (1-100 microM)
      reduced (22)Na(+) influx induced by veratridine, an activator of voltage
      dependent Na(+) channels. Carvedilol also suppressed veratridine-induced
      (45)Ca(2+) influx and catecholamine secretion in a concentration-dependent manner
      similar to that of (22)Na(+) influx. Prolonged exposure of the cells to 10 microM
      carvedilol increased [(3)H]saxitoxin ([(3)H]STX) binding, which reached a plateau
      at 12 h and was still observed at 48 to 72 h. Scatchard analysis of [(3)H]STX
      binding revealed that carvedilol increased the B(max) value (control, 14.9 +/-
      0.9 fmol/10(6) cells; carvedilol, 23.8 +/- 1.2 fmol/10(6) cells) (n = 3, P <
      0.05) without altering the K(d) value, suggesting a rise in the number of cell
      surface Na(+) channels. The increase in [(3)H]STX binding by carvedilol was
      prevented by cycloheximide, an inhibitor of protein synthesis, whereas carvedilol
      changed neither alpha- nor beta(1)-subunit mRNA levels of Na(+) channels. The
      carvedilol-induced increase of [(3)H]STX binding was abolished by brefeldin A and
      H-89, inhibitors of intracellular vesicular trafficking of proteins from the
      trans-Golgi network and of cyclic AMP-dependent protein kinase (protein kinase
      A), respectively. The present findings suggest that short-term treatment with
      carvedilol reduces the activity of Na(+) channels, whereas prolonged exposure to
      carvedilol up-regulates cell surface Na(+) channels. This may add new
      pharmacological effects of carvedilol to our understanding in the treatment of
      heart failure and hypertension.

PMID- 12065720
TI  - Differential internalization of the prostaglandin f(2alpha) receptor isoforms:
      role of protein kinase C and clathrin.
AB  - FP prostanoid receptors are G-protein-coupled receptors that mediate the actions
      of prostaglandin F(2alpha) (PGF(2alpha)). Alternative mRNA splicing gives rise to
      two isoforms, FP(A) and FP(B), which are identical except for their intracellular
      carboxyl termini. In this study, we examined the internalization of recombinant
      FLAG-epitope-tagged FP(A) and FP(B) receptors that were stably expressed in human
      embryonic kidney-293 cells. Cell surface receptors on live cells were labeled
      with anti-FLAG antibodies either in the presence or absence of PGF(2alpha) and
      were examined by immunofluorescence microscopy. In the absence of PGF(2alpha),
      FP(A)-expressing cells were labeled predominantly on the cell surface; however,
      FP(B)-expressing cells were labeled on both the cell surface and intracellularly,
      indicating constitutive internalization of the FP(B) isoform. After treatment
      with PGF(2alpha), FP(A)-expressing cells were labeled intracellularly, reflecting
      receptor internalization, which could be mimicked with phorbol 12-myristyl 13
      acetate (PMA), an activator of protein kinase C (PKC). Pretreatment of FP(A)
      expressing cells with Go 6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5
      oxo-5H-indolo[2,3-a]pyrrolo[3,4-c]carbozole], an inhibitor of PKC, blocked both
      PGF(2alpha)- and PMA-induced receptor internalization. However, Go 6976 did not
      block constitutive internalization of the FP(B) isoform, suggesting that the
      mechanisms of receptor internalization differ between the FP(A) and FP(B)
      isoforms. Furthermore, pretreatment with sucrose, an inhibitor of clathrin
      dependent internalization, blocked PGF(2alpha)-induced internalization of the
      FP(A) isoform but did not block constitutive internalization of the FP(B)
      isoform. In conclusion, the FP(A) receptor isoform shows an agonist-induced
      internalization involving PKC and clathrin, whereas the FP(B) isoform undergoes
      agonist-independent internalization that does not involve PKC or clathrin.

PMID- 12065721
TI  - Enhancement of L-cystine transport activity and its relation to xCT gene
      induction at the blood-brain barrier by diethyl maleate treatment.
AB  - The purpose of the present study was to elucidate the mechanism of enhancement of
      L-cystine uptake at the blood-brain barrier (BBB). The uptake of [(14)C]L-cystine
      and [(3)H]L-glutamic acid (L-Glu) was determined using a mouse brain endothelial
      cell line (MBEC4) as an in vitro BBB model. The mRNA levels of L-cystine/L-Glu
      exchanger, system x(c)(-), which consists of xCT and 4F2hc, were determined by
      quantitative real-time reverse transcription-polymerase chain reaction analysis.
      The [(14)C]L-cystine uptake by MBEC4 cells appeared to be mediated via an Na(+)
      independent saturable process. The corresponding Michaelis-Menten constant (K(m))
      was 63.7 microM. In the presence of L-Glu, there was competitive inhibition with
      an inhibition constant (K(i)) of 83.5 microM. [(3)H]L-Glu uptake in the absence
      of Na(+) was saturable with a K(m) of 48.1 microM, and it exhibited competitive
      inhibition with a K(i) of 24.9 microM in the presence of L-cystine. The mutual
      inhibition between L-cystine and L-Glu and the type of inhibition suggest that
      system x(c)(-) operates in MBEC4 cells. The xCT and 4F2hc mRNAs were expressed in
      MBEC4 cells and, following diethyl maleate (DEM) treatment, the xCT mRNA level
      and L-cystine uptake in MBEC4 cells were enhanced in parallel with an increase in
      DEM concentration (up to 500 microM). Concomitantly, the glutathione
      concentration in MBEC4 cells was increased. In conclusion, system x(c)(-)
      mediated L-cystine uptake takes place in MBEC4 cells. L-Cystine transport via
      system x(c)(-) at the BBB is likely to be induced under oxidative stress
      conditions following DEM treatment due to enhanced transcription of the xCT gene.

PMID- 12065722
TI  - Atorvastatin treatment induced peroxisome proliferator-activated receptor alpha
      expression and decreased plasma nonesterified fatty acids and liver triglyceride
      in fructose-fed rats.
AB  - We aimed to investigate the effect of atorvastatin (5 and 30 mg/kg/day for 2
      weeks) on hepatic lipid metabolism in a well established model of dietary
      hypertriglyceridemia, the fructose-fed rat. Fructose feeding (10% fructose in
      drinking water for 2 weeks) induced hepatic lipogenesis and reduced peroxisome
      proliferator-activated receptor alpha (PPARalpha) expression and fatty acid
      oxidation. As a result, plasma and liver triglyceride and plasma apolipoprotein B
      (apoB) levels were increased. Atorvastatin, 5 and 30 mg/kg during 2 weeks,
      markedly reduced plasma triglyceride, but decreased apoB levels only at the
      highest dose tested (50%). Triglyceride biosynthetic enzymes and microsomal
      triglyceride transfer protein were unchanged, whereas liver PPARalpha, acyl-CoA
      oxidase, and carnitine palmitoyltransferase I mRNA levels (1.9-, 1.25-, and 3.4
      fold, respectively) and hepatic fatty acid beta-oxidation activity (1.25-fold)
      were increased by atorvastatin at 30 mg/kg. Furthermore, hepatic triglyceride
      content (45%) and plasma nonesterified fatty acids (NEFAs) (49%) were reduced.
      These results show for the first time that liver triglyceride increase in
      fructose-fed rats is linked to decreased expression of PPARalpha, which is
      prevented by atorvastatin treatment. The increase in PPARalpha expression caused
      by atorvastatin was associated with reduced liver triglyceride and plasma NEFA
      levels.

PMID- 12065723
TI  - Reconsideration of 5-hydroxytryptamine (5-HT)(7) receptor distribution using
      [(3)H]5-carboxamidotryptamine and [(3)H]8-hydroxy-2-(di-n-propylamino)tetraline:
      analysis in brain of 5-HT(1A) knockout and 5-HT(1A/1B) double-knockout mice.
AB  - The characterization and anatomical distribution of 5-hydroxytryptamine (5-HT)(7)
      receptor binding sites in brain tissue has been hampered by the lack of a
      specific radioligand. In the present autoradiographic study, we took advantage of
      5-HT(1A) knockout and 5-HT(1A/1B) double-knockout mice to revisit the
      pharmacological characterization and anatomical localization of 5-HT(7) binding
      sites in mouse brain using [(3)H]5-carboxamidotryptamine (5-CT) and [(3)H]8
      hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT). The distribution pattern of
      [(3)H]5-CT binding sites (2 nM) in the brain of mice lacking the 5-HT(1A/1B)
      receptor was scarce and confined to the septum, globus pallidus, thalamus,
      hypothalamus, amygdala, cortex, and substantia nigra. The low densities of
      [(3)H]5-CT binding sites detected in septum, thalamus, hypothalamus, amygdala,
      and cortex were displaced by 10 microM of the selective 5-HT(7) receptor
      antagonist (R)-3-(2-(2-(4-methylpiperidin-1-yl) ethyl)pyrrolidine-1-sulfonyl)
      phenol (SB-269970). The SB-269970-insensitive [(3)H]5-CT binding sites detected
      in globus pallidus and substantia nigra of 5-HT(1A/1B) knockout mice were
      displaced by N-[3-(2-dimethylamino)ethoxy-4-methoxy-phenyl]-2'-methyl-4'- (5
      methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide hydrochloride (SB
      216641) (1 microM), demonstrating the 5-HT(1D) nature of these binding sites. In
      contrast to the low densities of [(3)H]5-CT binding sites, high-to-moderate
      densities of [(3)H]8-OH-DPAT binding sites (10 nM) were found throughout the
      brain of 5-HT(1A) and 5-HT(1A/1B) knockout mice (olfactory system, septum,
      thalamus, hypothalamus, amygdala, CA3 field of the hippocampus, cortical mantle,
      and central gray). These [(3)H]8-OH-DPAT binding sites were displaced by 10
      microM SB-269970, risperidone, and methiothepin but not by pindolol, N-tert-butyl
      3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpropanamide (WAY- 100135), or
      citalopram. We conclude that despite its high affinity for the 5-HT(7) receptor
      in tissue homogenates, [(3)H]5-CT is not a good tracer for measuring 5-HT(7)
      receptor binding sites autoradiographically. Also, the lower affinity ligand
      [(3)H]8-OH-DPAT is a much better tracer for autoradiographic studies at the 5
      HT(7) receptor binding sites.

PMID- 12065724
TI  - Hydrolysis of N-methyl-D-aspartate receptor-stimulated cAMP and cGMP by PDE4 and
      PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and
      hippocampus.
AB  - Stimulation of N-methyl-D-aspartate (NMDA) receptors on neurons activates both
      cAMP and cGMP signaling pathways. Experiments were carried out to determine which
      phosphodiesterase (PDE) families are involved in the hydrolysis of the cyclic
      nucleotides formed via this mechanism, using primary neuronal cultures prepared
      from rat cerebral cortex and hippocampus. The nonselective PDE inhibitor 3
      isobutyl-1-methylxanthine (IBMX) potentiated the ability of NMDA to increase cAMP
      and cGMP. However, among the family-selective inhibitors, only the PDE4 inhibitor
      rolipram enhanced the ability of NMDA to increase cAMP in the neurons. In
      contrast, only the PDE2 inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA)
      enhanced the ability of NMDA to increase cGMP. Neither adenosine nor an adenosine
      deaminase inhibitor mimicked the effect of EHNA; this suggests that EHNA's
      inhibition of PDE2, not its effects on adenosine metabolism, mediates its effects
      on NMDA-stimulated cGMP concentrations. The PDE inhibitor-augmented effects of
      NMDA on cAMP and cGMP formation were antagonized by 5-methyl-10,11-dihydro-5H
      dibenzo[a,d] cyclohepten-5,10-imine maleate (MK-801), verifying NMDA receptor
      mediation. In contrast, only NMDA-mediated cGMP formation was affected by
      altering either nitric oxide signaling or guanylyl cyclase; this suggests that
      NMDA-induced changes in cAMP are not secondary to altered cGMP concentrations.
      Overall, the present findings indicate that cAMP and cGMP formed in neurons as a
      result of NMDA receptor stimulation are hydrolyzed by PDE4 and PDE2,
      respectively. Selective inhibitors of the two PDE families will differentially
      affect the functional consequences of activation of these two signaling pathways
      by NMDA receptor stimulation.

PMID- 12065725
TI  - A novel method to assess initial sensitivity and acute functional tolerance to
      hypnotic effects of ethanol.
AB  - Loss of righting reflex (LRR) has traditionally been used to estimate hypnotic
      sensitivity to ethanol in rodents. Traditional methods of monitoring ethanol
      induced sedation seems to lack accuracy in estimating blood ethanol concentration
      (BEC) at initial LRR, a measure of initial sensitivity. Herein, we present a
      novel method that improves detection of the onset of LRR by using a new apparatus
      and a loss-of-function criterion of 5 s. DBA/2J and C57BL/6J mice were placed in
      cylindrical restrainers after injection of 3 g/kg (20% v/v) ethanol. Restrainers
      were then turned until mice were no longer able to right themselves within 5 s
      from a position on their back, which represented the endpoint of the initial loss
      of righting reflex. Initial sensitivity and acute functional tolerance (AFT) to
      ethanol were assessed in the same group of mice by quantifying BEC at the initial
      loss and subsequent recoveries of righting reflex over four sequential injections
      [3 g/kg + (3 x 0.5 g/kg)]. Initial brain sensitivity was calculated from BEC at
      the first LRR, using the parameters of ethanol uptake kinetics. These values of
      initial sensitivity were similar for the two strains. On the other hand, DBA/2J
      mice recovered at higher BEC than C57BL/6J animals. AFT calculated as a
      difference between the maximum BEC at any recovery and the value of initial
      sensitivity was greater in DBA/2J mice. These results show that the novel method
      is a sensitive tool for the measurement of initial sensitivity and detection of
      AFT to the hypnotic effects of ethanol.

PMID- 12065727
TI  - C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting
      with a new gastrin binding site.
AB  - It is well known that the amidated C-terminal part of gastrin is crucial for its
      interaction with the classical seven transmembrane domain receptors CCK-1 or CCK
      2. Nevertheless, over the past 10 years, several groups have characterized new
      binding sites using peptides related to gastrin (particularly glycine-extended
      forms of gastrin) on various tumoral and nontumoral cell lines. In the present
      study, we focused on the human astrocytic tumoral cell line U373. Although it has
      been described that gastrin was able to inhibit the motility of these cells, we
      were unable to detect any classical CCK/gastrin receptor. On the other hand, by
      using the radiolabeled C-terminal heptapeptide of gastrin ((125)I-G-7), we
      evidenced a new binding site that possessed a pharmacological profile different
      from the classical CCK/gastrin receptors. This new gastrin binding site seemed to
      be coupled to G proteins and be implicated in c-Fos transcription gene. Moreover,
      we showed that G-7 was able to induce a strong inhibition of U373 cell migration,
      a crucial biological effect when we know that astrocytoma cells' migration in
      brain parenchyma constitutes a major feature of malignancy in astrocytic tumors.

PMID- 12065726
TI  - Antagonism of the antinociceptive and discriminative stimulus effects of heroin
      and morphine by 3-methoxynaltrexone and naltrexone in rhesus monkeys.
AB  - It has been suggested that heroin and morphine may act on different opioid
      receptor populations in rodents. In support of this hypothesis, the opioid
      antagonist 3-methoxynaltrexone was reported to be more potent as an antagonist of
      the antinociceptive effects of heroin than of morphine in mice and rats. To
      assess the generality of this finding across species and experimental endpoints,
      the present study compared the potencies of naltrexone and 3-methoxynaltrexone as
      antagonists of heroin and morphine in two behavioral assays in rhesus monkeys. In
      the thermal nociception study, tail-withdrawal latencies were measured from water
      heated to 50 degrees C. In the heroin discrimination study, monkeys were trained
      to discriminate 0.1 mg/kg heroin from saline in a two-key, food-reinforced drug
      discrimination procedure, and percentage of heroin-appropriate responding and
      response rates were measured. Both heroin and morphine produced dose-dependent
      antinociception, increases in percentage of heroin-appropriate responding, and
      decreases in response rates. Heroin was approximately 20-fold more potent than
      morphine. Naltrexone (0.032-0.1 mg/kg) was equipotent in antagonizing all effects
      of heroin and morphine (pA(2) values = 7.90-8.22). 3-Methoxynaltrexone (0.1-3.2
      mg/kg) was also equipotent in antagonizing the antinociceptive, discriminative
      stimulus, and rate-suppressant effects of heroin and morphine; however, 3
      methoxynaltrexone was approximately 100-fold less potent than naltrexone
      (pA(2)/pK(B) values = 5.96-6.36). These results suggest that heroin and morphine
      act on pharmacologically similar populations of opioid receptors in rhesus
      monkeys, and also indicate that 3-methoxynaltrexone does not differentially
      antagonize the effects of heroin and morphine in rhesus monkeys.

PMID- 12065728
TI  - Antiarrhythmic efficacy of combined I(Ks) and beta-adrenergic receptor blockade.
AB  - Suppression of malignant ventricular arrhythmias by selective blockade of the
      cardiac slowly activating delayed rectifier current (I(Ks)) has been demonstrated
      with the benzodiazepine L-768673 [(R)-2-(2,4-trifluoromethyl-phenyl)-N-[2-oxo-5
      phenyl-1-(2,2,2-trifluoro-ethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3
      yl]acetamide] in canine models of recent and healed myocardial infarction. The
      present study extends the initial antiarrhythmic assessment of I(Ks) blockade by
      demonstrating prevention of ischemic malignant arrhythmias in dogs with recent
      (8.0 +/- 0.4 days) anterior myocardial infarction with the coadministration of a
      subeffective dose of L-768673 and a subeffective, minimally beta-adrenergic
      blocking dose of timolol. Administered individually, neither 0.3 microg/kg i.v. L
      768673 nor 1.0 microg/kg i.v. timolol prevented the induction of ventricular
      tachyarrhythmia (VT) by programmed ventricular stimulation (PVS) or the
      development of malignant ventricular arrhythmia in response to acute coronary
      artery thrombosis. In contrast, coadministration of 0.3 microg/kg i.v. L-768673 +
      1.0 microg/kg i.v. timolol suppressed the induction of VT by PVS (8/10, 80%
      rendered noninducible versus 1/10, 10% noninducible in vehicle group; p < 0.01)
      and prevented the development of acute ischemic lethal arrhythmias (3/10, 30%
      incidence versus 8/10, 80% incidence in vehicle group; p < 0.05). Concomitant
      administration of low-dose L-768673 + timolol produced modest increases in QTc
      and paced QT intervals (4.5 +/- 1.2 and 5.5 +/- 1.4%; both p < 0.01), increases
      in noninfarct zone relative and effective refractory periods (7.0 +/- 1.7 and
      12.3 +/- 3.0%; both p < 0.01), and lesser increases in infarct zone relative and
      effective refractory periods (5.3 +/- 1.6 and 5.8 +/- 1.4%; both p < 0.01). These
      findings suggest that concomitant low-dose I(Ks) and beta-adrenergic blockade may
      constitute a potential pharmacologic strategy for prevention of malignant
      ischemic ventricular arrhythmias.

PMID- 12065729
TI  - Low-molecular-weight heparins inhibit CCL21-induced T cell adhesion and
      migration.
AB  - The chemokine CCL21, also known as Exodus-2/6-Ckine/secondary lymphoid-tissue
      chemokine/T cell activator protein-4, is the most potent stimulator of T cell
      migration and adhesion yet described. Endothelial heparin-like glycosaminoglycans
      (GAGs) are thought to present chemokines at sites of inflammation, maintaining a
      local concentration gradient to which leukocytes can respond. In contrast, this
      study found that GAGs markedly inhibit the ability of CCL21 to stimulate T cell
      adhesion and chemotaxis. Enzymes, such as heparinase, that split GAGs into
      component-sulfated saccharides abrogate this inhibition, suggesting a mechanism
      for local tissue regulation of CCL21 function. Low-molecular-weight heparins also
      strongly inhibit CCL21 adhesion and chemotaxis. Therefore, low-molecular-weight
      heparins may be effective therapeutic agents in decreasing the pathology of T
      cell-infiltrative autoimmune diseases by targeting the CCL21 regulation of T cell
      infiltration.

PMID- 12065730
TI  - 4-hydroxynonenal decreases interleukin-6 expression and protein production in
      primary rat Kupffer cells by inhibiting nuclear factor-kappaB activation.
AB  - Kupffer cells have been documented to play an important role in the early events
      of liver injury and regeneration by releasing biologically active mediators such
      as interleukin-6 (IL-6). 4-Hydroxy-trans-2-nonenal (4-HNE), a major end product
      of lipid peroxidation, has multiple cytotoxic effects and is implicated in
      chemical-induced liver injury. Consequently, the purpose of this study was to
      evaluate the ability of 4-HNE to modulate IL-6 production in isolated primary rat
      Kupffer cells. 4-HNE (0.1-10 microM) reduced both lipopolysaccharide (LPS)
      induced IL-6 protein production and mRNA levels. The role of nuclear factor
      kappaB (NF-kappaB) in IL-6 induction was elucidated using Kupffer cells
      transduced in vitro with a recombinant adenovirus containing a IkappaBalpha super
      repressor resistant to phosphorylation and degradation (Ad5IkappaB). Using this
      system, LPS-induced IL-6 protein production was inhibited by 65% in Ad5IkappaB
      infected cells. The treatment of Kupffer cells for 1 h with 4-HNE followed by
      stimulation for 1 h with LPS (500 ng/ml) resulted in a concentration-dependent
      decrease in NF-kappaB activation. Similarly, decreased NF-kappaB activity in
      these cells paralleled a reduction in IkappaBalpha mRNA levels. Furthermore, upon
      LPS stimulation, 4-HNE stabilized IkappaBalpha, which corresponded to a decrease
      in phosphorylated IkappaBalpha. At lower 4-HNE concentrations (0-5 microM),
      interactions between p65 and IkappaBalpha proteins were maintained as detected by
      immunoprecipitation-immunoblot analyses. In conclusion, these data suggest that 4
      HNE inhibits IL-6 production in rat Kupffer cells by preventing activation of the
      NF-kappaB pathway and suppressing IkappaBalpha phosphorylation. These results
      have functional implications in that 4-HNE may interfere with the ability of
      Kupffer cells to produce cytokines proposed to play an important role in liver
      regeneration.

PMID- 12065731
TI  - Skeletal efficacy with parathyroid hormone in rats was not entirely beneficial
      with long-term treatment.
AB  - We report the consequences of prolonged treatment with recombinant human
      parathyroid hormone (1-34) (PTH) in male and ovariectomized female rats with
      mature skeletons. Intact male and osteopenic, ovariectomized, female F-344 rats
      were evaluated after 1 year of treatment with 0, 8, or 40 microg/kg/day s.c. PTH.
      Males and females were about 6 months of age at study initiation; females were
      ovariectomized (Ovx) for 5 weeks before initiation of PTH treatment. PTH did not
      affect the survival of either intact males or ovariectomized females. Qualitative
      histopathology showed expected changes associated with aging in kidneys and
      proximal tibiae, with no treatment-related anomalies after 1 year of PTH
      administration. PTH slightly increased the femoral length of ovariectomized
      females but not that of males. No significant differences in femoral length were
      observed between sham and Ovx controls. Proximal femora of the males and
      ovariectomized females given the high dose of 40 microg/kg showed 211 and 186%
      greater trabecular bone area, 118 and 94% greater cortical thickness, 170 and
      189% greater trabecular number, and 321 and 404% greater connectivity (node-to
      node struts) compared with respective vehicle controls. Increased trabecular and
      endocortical surface apposition coincided with a 78 and 70% loss of marrow space
      for males and females treated with PTH, respectively. Biomechanical strength
      (ultimate load) of the femoral neck increased by 73 and 76%, respectively, in
      males and ovariectomized females. Cortical bone analyses of the femoral midshaft
      showed 105 and 72% increases in bone mineral content, 67 and 55% increases in
      bone mineral density, and 22 and 10% increases in cross-sectional area for males
      and ovariectomized females, respectively, with altered shape of femora.
      Biomechanical analyses of the midshaft showed substantial increases in strength
      and stiffness but a reduction in ultimate strain, which was likely due to the
      altered geometry of the midshaft for PTH groups. Aging effects on strength of
      vertebra and femoral midshaft were reversed by PTH treatment. In summary, the 1
      year treatment duration, which represents about 50% of lifetime, did not affect
      survival and was not associated with any treatment-related anomalies in the
      kidney or skeleton. PTH reversed the aging process in bones but not kidneys and
      substantially increased bone mass and strength to well beyond normally attained
      levels. However, compared with short-term studies reported previously, there
      seemed to be no advantages to extending PTH treatment to 12 months in rat bones.

PMID- 12065732
TI  - Open channel block by KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4
      dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] of the heterologously
      expressed human ether-a-go-go-related gene K+ channels.
AB  - KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N
      methylamino]ethane hydrochloride] is a newly synthesized class III antiarrhythmic
      drug and is known to be highly effective against various types of arrhythmias
      induced by coronary artery ligation, reperfusion, and programmed electrical
      stimulation. To understand the potential ionic mechanisms, we examined the
      effects of KCB-328, which encodes the rapidly activating delayed rectifier K(+)
      current in cardiac tissues, on human ether-a-go-go-related gene (HERG) channels
      expressed in Xenopus oocytes. The amplitudes of steady-state currents and tail
      currents of HERG were decreased by KCB-328 dose dependently. The decrease became
      more pronounced at more positive potential, suggesting that the block of HERG by
      KCB-328 is voltage-dependent. IC(50) values at -30, -20, -10, 0, +10, +20, +30,
      and +40 mV were 7.6 +/- 0.5, 4.8 +/- 0.4, 3.2 +/- 0.3, 2.1 +/- 0.3, 1.7 +/- 0.2,
      1.4 +/- 0.2, 1.3 +/- 0.1, and 1.2 +/- 0.1 microM, respectively. Induction of
      block depended on depolarization beyond the threshold for channel opening. In
      addition, time-dependent block developed slowly, with tau = 1.7 +/- 0.3 s (100
      microM) at 0 mV, and was delayed by a stronger depolarization to +80 mV, at which
      HERG channel is inactivated. We can conclude that KCB-328 preferentially blocks
      open (or activated) HERG channels. The block of HERG current might in part
      explain the underlying ionic mechanism for the antiarrhythmic and proarrhythmic
      effect of KCB-328.

PMID- 12065733
TI  - Blockade of human cardiac potassium channel human ether-a-go-go-related gene
      (HERG) by macrolide antibiotics.
AB  - Several macrolides have been reported to cause QT prolongation and ventricular
      arrhythmias such as torsades de pointes. To clarify the underlying ionic
      mechanisms, we examined the effects of six macrolides on the human ether-a-go-go
      related gene (HERG)-encoded potassium current stably expressed in human embryonic
      kidney-293 cells. All six drugs showed a concentration-dependent inhibition of
      the current with the following IC(50) values: clarithromycin, 32.9 microM;
      roxithromycin, 36.5 microM; erythromycin, 72.2 microM; josamycin, 102.4 microM;
      erythromycylamine, 273.9 microM; and oleandomycin, 339.6 microM. A metabolite of
      erythromycin, des-methyl erythromycin, was also found to inhibit HERG current
      with an IC(50) of 147.1 microM. These findings imply that the blockade of HERG
      may be a common feature of macrolides and may contribute to the QT prolongation
      observed clinically with some of these compounds. Mechanistic studies showed that
      inhibition of HERG current by clarithromycin did not require activation of the
      channel and was both voltage- and time-dependent. The blocking time course could
      be described by a first-order reaction between the drug and the channel. Both
      binding and unbinding processes appeared to speed up as the membrane was more
      depolarized, indicating that the drug-channel interaction may be affected by
      electrostatic responses.

PMID- 12065734
TI  - A novel phenylaminotetralin radioligand reveals a subpopulation of histamine H(1)
      receptors.
AB  - Previously, (-)-trans-1-phenyl-3-N,N-dimethylamino-1,2,3,4-tetrahydronaphthalene
      ([-]-trans-H(2)-PAT) was shown to activate stereospecifically histamine H(1)
      receptors coupled to modulation of tyrosine hydroxylase activity in guinea pig
      and rat forebrain in vitro and in vivo. Furthermore, the novel radioligand
      [(3)H](-)-trans-H(2)-PAT was shown to label selectively H(1) receptors in guinea
      pig and rat brain with high affinity (K(D), ~0.1 and 0.5 nM, respectively) and a
      B(max) about 50 and 15%, respectively, of that observed for the H(1) antagonist
      radioligand [(3)H]mepyramine. In the current study, [(3)H](-)-trans-H(2)-PAT
      labeled cloned guinea pig and human H(1) receptors in Chinese hamster ovary (CHO)
      cell membranes with high affinity (K(D), ~0.08 and 0.23 nM, respectively) and a
      B(max) about 15% of that observed for [(3)H]mepyramine. The binding of H(2)-PAT
      to H(1) receptors in both CHO-H(1) cell lines was stereoselective with the (-)
      trans-isomer having affinity (K(i), ~1.5 nM) about 4-, 20-, and 50-times higher
      than the (-)-cis-, (+)-trans-, and (+)-cis-isomers, respectively; the affinity of
      (-)-trans-H(2)-PAT was unaffected by excess GTP. In functional assays, (-)-trans
      H(2)-PAT was a full antagonist of histamine H(1)-mediated stimulation of
      phospholipase C (PLC) and [(3)H]inositol phosphates (IP) formation in CHO-H(1)
      cells, a full inverse agonist of constitutively active H(1) receptors in COS-7
      H(1) cells, and a full competitive antagonist (pA(2) = 9.2) of histamine H(1)
      mediated contraction of guinea pig ileum. It is concluded that (-)-trans-H(2)-PAT
      is an antagonist at H(1) receptors coupled to PLC/IP formation and smooth muscle
      contraction. Meanwhile, the observation that [(3)H](-)-trans-H(2)-PAT labels only
      a subpopulation of H(1) receptors and that (-)-trans-H(2)-PAT activates H(1)
      receptors coupled to modulation of tyrosine hydroxylase suggests that there may
      be post-translational H(1) receptor heterogeneity.

PMID- 12065735
TI  - Schedule-dependent interaction between vinblastine and cisplatin in Ehrlich
      ascites tumors in mice.
AB  - Information on the in vivo antitumor efficiency of the combination of Vinca
      alkaloids in animal tumor models, especially vinblastine (VLB) with cisplatin
      [cis-diamminedichloroplatinum(II); CDDP] is very limited. Therefore, the aim of
      our study was to explore whether antitumor schedule dependence exists for the
      combination of CDDP and VLB on i.p. Ehrlich ascites tumors in mice. Animals were
      treated 3 days after tumor transplantation with VLB (0.006 mg/kg) or CDDP (0.05
      mg/kg) alone, VLB followed by CDDP, and CDDP followed by VLB. The time interval
      between i.p. injections of the drugs was 24 h. Cell number was measured by
      counting viable cells using the trypan blue exclusion assay, cell platinum
      content by electrothermal atomic absorption spectrometry, DNA distribution
      pattern using flow cytometry, apoptosis by flow-cytometric terminal
      deoxynucleotidyl transferase dUTP nick-end labeling assay, and cell morphology.
      Combination of CDDP and VLB resulted in additive interaction when VLB preceded
      CDDP as determined from cell survival data 24 h after completion of the therapy
      and in increased platinum content (two times) compared with the same combination
      in a reverse schedule (CDDP given before VLB), which resulted in antagonism. None
      of the treatment combinations induced apoptosis. We propose that the observed
      increase in antitumor effectiveness is mainly due to higher platinum accumulation
      in tumor cells, which we unambiguously demonstrated by measurement of platinum
      content in the tumor cells, leading to increased cytotoxicity as well as to cell
      cycle-dependent effects of VLB and CDDP.

PMID- 12065736
TI  - High salt intake impairs vascular nitric oxide/cyclic guanosine monophosphate
      system in spontaneously hypertensive rats.
AB  - In aortas of spontaneously hypertensive rats (SHRs), excessive dietary salt
      causes down-regulation of soluble guanylate cyclase (sGC) followed by decreased
      cyclic GMP production, which leads to impairment of the vascular relaxation
      response to nitric oxide (NO). The present study aimed to elucidate whether this
      impaired NO/cyclic GMP system results secondarily from increased blood pressure
      or from an effect of the salt itself. The antihypertensive drug nifedipine was
      used on 4-week-old SHRs that received a normal-salt diet or a high-salt diet for
      4 weeks. Treatment with nifedipine (30 mg/kg/day, p.o.) reduced the increased
      blood pressure of SHRs fed the high-salt diet to the level of SHRs fed the normal
      salt diet. In aortic rings from SHRs fed the high-salt diet, not only endothelium
      dependent relaxations but also endothelium-independent relaxations were
      significantly impaired. However, these impairments were not alleviated by
      treatment with nifedipine. Furthermore, nifedipine did not prevent the increase
      in protein levels of endothelial NO synthase and the decrease in the protein
      levels of sGC in aortas from SHRs fed the high-salt diet. These alterations by
      high salt intake were restored after replacement with the normal-salt diet for 4
      additional weeks. These results indicate that in SHRs given excessive dietary
      salt, normalization of salt intake but not blood pressure reduction can
      ameliorate alterations in the NO/cyclic GMP system. High salt intake may directly
      affect the vascular smooth muscle and cause impairment of the relaxation response
      to NO.

PMID- 12065737
TI  - Putative conventional protein kinase C inhibitor Godecke 6976 [12-(2-cyanoethyl)
      6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole]
      stimulates transglutaminase activity in primary mouse epidermal keratinocytes.
AB  - Much data in the literature suggest a role for protein kinase C (PKC) in
      regulating keratinocyte proliferation and differentiation. Nevertheless, the
      exact role of this family of isoenzymes is unclear, since PKC agonists (e.g.,
      phorbol esters) are known to stimulate expression of both proliferative and
      differentiative markers in keratinocytes. Similarly, PKC inhibitors have been
      demonstrated both to inhibit [2-[1-3(aminopropyl)indol-3-yl]-3(1-methyl-1H-indol
      3-yl)maleimide, acetate (Ro 31-7549) and 3-[1-[3-(amidinothio)propyl-1H-indol-3
      (1-methyl-1H-indol-3yl) maleimide (Ro 31-8220)] and to induce (staurosporine)
      keratinocyte differentiation. In this study, we examined the role of the PKC
      inhibitor, Godecke 6976 (Go6976) [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13
      methyl-5-oxo-5H-indolo(2,3-a)pyrrolo (3,4-c)-carbazole], on keratinocyte
      proliferation, as measured by DNA synthesis, and differentiation, as monitored by
      transglutaminase activity. This compound is reported to be selective for the
      conventional PKC isoforms, of which keratinocytes express only PKCalpha, and for
      protein kinase D (PKD; also known as PKCmu). We report that Go6976 stimulated
      transglutaminase activity. Consistent with this effect, Go6976 also potently
      inhibited [(3)H]thymidine incorporation (a half-maximal inhibitory concentration
      of approximately 0.1 microM). In addition, Go6976 (1 microM) was able to enhance
      the stimulation of transglutaminase activity by 1,25-dihydroxyvitamin D(3) but
      had no effect on D(3)-induced expression of keratin-1. Conversely, Go6983 [2-[1
      (3-dimethylaminopropy)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide], a
      similar compound that also selectively inhibits conventional PKCalpha, but not
      PKD, had little or no effect on DNA synthesis or transglutaminase activity (up to
      1 microM). The effect of Go6976 was not due to cytotoxicity as its effect on
      thymidine incorporation was largely reversible, and its stimulation of
      transglutaminase activity could be inhibited by another general PKC inhibitor,
      bisindolylmaleimide I. Therefore, our results suggest a proproliferative,
      antidifferentiative role for PKD in epidermal maturation.

PMID- 12065738
TI  - Characterization of the diarylether sulfonylester (-)-(R)-3-(2
      hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-sulfonate (BAY 38-7271) as a
      potent cannabinoid receptor agonist with neuroprotective properties.
AB  - (-)-(R)-3-(2-Hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-sulfonate (BAY
      38-7271) is a new high-affinity cannabinoid receptor subtype 1 (CB1 receptor)
      ligand (K(i) = 0.46-1.85 nM; rat brain, human cortex, or recombinant human CB1
      receptor), structurally unrelated to any cannabinoid receptor ligand known so
      far. BAY 38-7271 was characterized as a CB1 receptor agonist in 5-[gamma(35)S]
      thiophosphate triethylammonium salt binding assays using rat or human CB1
      receptors. In the rat hypothermia assay, BAY 38-7271 induced a dose-dependent
      reduction in body temperature (minimal effective dose = 6 microg/kg, i.v.);
      whereas in rats trained to discriminate the CB1/CB2 receptor agonist (-)-cis-3-[2
      hydroxy-4(1,1-dimethyl-heptyl)phenyl]-trans-4-(3-hydroxypropyl) cyclohexanol (CP
      55,940; 0.03 mg/kg, i.p.) from vehicle, BAY 38-7271 induced complete
      generalization (3 microg/kg, i.v.). In both in vivo models, a specific CB1
      receptor-mediated mechanism was confirmed by demonstrating that the effects of CP
      55,940 and BAY 38-7271 were blocked by pretreatment with the selective CB1
      receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)
      4-methyl-1H-pyrazole-3-carboxamidehydrochloride. In the rat traumatic brain
      injury model, BAY 38-7271 demonstrated highly potent and efficient
      neuroprotective properties when administered as a 4-h infusion immediately after
      induction of subdural hematoma (70% infarct volume reduction at 100 ng/kg/h).
      Even when applied with a 3-h delay, a significant neuroprotective efficacy could
      be observed (59% infarct volume reduction at 300 ng/kg/h). The neuroprotective
      potential of BAY 38-7271 was confirmed in a rat model of focal cerebral ischemia
      induced by permanent occlusion of the middle cerebral artery. It is concluded
      that the CB1/CB2 receptor agonist BAY 38-7271 shows pronounced neuroprotective
      properties that do not result from drug-induced hypothermia and that occur in a
      dose range devoid of typical cannabinoid-like side effects.

PMID- 12065739
TI  - Metabolism and disposition of resveratrol in rats: extent of absorption,
      glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model.
AB  - Pharmacokinetics of trans-resveratrol in its aglycone (RES(AGL)) and glucuronide
      (RES(GLU)) forms were studied following intravenous (15 mg/kg i.v.) and oral (50
      mg/kg p.o.) administration of trans-resveratrol in a solution of beta
      cyclodextrin to intact rats. In addition, the enterohepatic recirculation of
      RES(AGL) and RES(GLU) was assessed in a linked-rat model. Multiple plasma and
      urine samples were collected and concentrations of RES(AGL) and RES(GLU) were
      determined using an electrospray ionization-liquid chromatography/tandem mass
      spectrometry method. After i.v. administration, plasma concentrations of RES(AGL)
      declined with a rapid elimination half-life (T(1/2), 0.13 h), followed by sudden
      increases in plasma concentrations 4 to 8 h after drug administration. These
      plasma concentrations resulted in a significant prolongation of the terminal
      elimination half-life of RES(AGL) (T(1/2TER), 1.31 h). RES(AGL) and RES(GLU) also
      displayed sudden increases in plasma concentrations 4 to 8 h after oral
      administration, with T(1/2TER) of 1.48 and 1.58 h, respectively. RES(AGL)
      bioavailability was 38% and its exposure was approximately 46-fold lower than
      that of RES(GLU) (AUC(inf), 7.1 versus 324.7 micromol.h/l). Enterohepatic
      recirculation was confirmed in the linked-rat model since significant plasma
      concentrations of RES(AGL) and RES(GLU) were observed in bile-recipient rats at 4
      to 8 h. The percentages of the exposures of RES(AGL) and RES(GLU) that were due
      to enterohepatic recirculation were 24.7 and 24.0%, respectively. The fraction of
      drug excreted in the urine over a period of 12 h was negligible. These results
      confirm that RES(AGL) is bioavailable and undergoes extensive first-pass
      glucuronidation, and that enterohepatic recirculation contributes significantly
      to the exposure of RES(AGL) and RES(GLU) in rats.

PMID- 12065740
TI  - 8-Carboxamidocyclazocine: a long-acting, novel benzomorphan.
AB  - To obtain benzomorphans with a longer duration of action that may be potential
      therapeutics for treating cocaine abuse, 8-carboxamidocyclazocine was
      synthesized. The pharmacological properties of 8-carboxamidocyclazocine were
      compared with the parent compound cyclazocine. Changing the 8-hydroxyl group on
      cyclazocine to an 8-carboxamido group resulted in only a 2-fold decrease in the
      affinity of the compound for the kappa-receptor, and no change in the affinity
      for the mu-opioid receptor, with both compounds having K(i) values of less than 1
      nM, based on radioligand binding assays. In the guanosine 5'-O -(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assay, the two compounds
      produced moderate stimulation of GTP binding to the human kappa- and mu
      receptors. When given by i.c.v. injection, the compounds produced less than 60%
      antinociception in the mouse 55 degrees C warm-water tail-flick test. However, in
      the mouse writhing test, the compounds had high potency in producing
      antinociception. Antinociception induced by either 8-carboxamidocyclazocine or
      cyclazocine was mediated by both kappa- and mu-opioid receptors. Cyclazocine
      acted as a mu-antagonist in addition to its agonist properties at the mu
      receptor, as measured by the inhibition of morphine-induced antinociception. In
      contrast, 8-carboxamidocyclazocine did not inhibit morphine-induced
      antinociception, demonstrating that it was not a mu-opioid receptor antagonist in
      this assay. An i.p. injection of an ED(70) dose of 8-carboxamidocyclazocine
      produced antinociception that lasted for 15 h in contrast to cyclazocine, which
      produced antinociception, lasting 2 h. 8-Carboxamidocyclazocine is a novel, long
      acting benzomorphan, which possesses pharmacological properties that are distinct
      from the properties of cyclazocine.

PMID- 12065741
TI  - Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human
      dopamine D2 receptors.
AB  - Aripiprazole is the first next-generation atypical antipsychotic with a mechanism
      of action that differs from currently marketed typical and atypical
      antipsychotics. Aripiprazole displays properties of an agonist and antagonist in
      animal models of dopaminergic hypoactivity and hyperactivity, respectively. This
      study examined the interactions of aripiprazole with a single population of human
      D2 receptors to clarify further its pharmacologic properties. In membranes
      prepared from Chinese hamster ovary cells that express recombinant D2L receptors,
      aripiprazole bound with high affinity to both the G protein-coupled and uncoupled
      states of receptors. Aripiprazole potently activated D2 receptor-mediated
      inhibition of cAMP accumulation. Partial receptor inactivation using the
      alkylating agent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ)
      significantly reduced the maximum effect of aripiprazole on inhibition of cAMP
      accumulation. This effect was seen with concentrations of EEDQ that did not alter
      the maximal inhibitory effect of dopamine. Consistent with the expected effects
      of a partial agonist, increasing concentrations of aripiprazole blocked the
      action of dopamine with maximal blockade equal to the agonist effect of
      aripiprazole alone. The efficacy of aripiprazole relative to that of dopamine
      varied from 25% in cells that lacked spare receptors for dopamine to 90% in cells
      with receptor reserve. These results, together with previous studies
      demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A
      receptors and antagonist activity at 5-HT2A receptors, support the identification
      of aripiprazole as a dopamine-serotonin system stabilizer. The receptor activity
      profile may underlie the unique activity of aripiprazole in animals and its
      antipsychotic activity in humans.

PMID- 12065742
TI  - (E)-2(R)-[1(S)-(Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'
      (methanesulfonyl)-4-methylvalerohydrazide (Ro 32-7315), a selective and orally
      active inhibitor of tumor necrosis factor-alpha convertase.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a cytokine secreted by inflammatory
      cells, has been implicated in several inflammatory disease states. (E)-2(R)-[1(S)
      (Hydroxycarbamoyl)-4-phenyl-3-butenyl]-2'-isobutyl-2'-(methanesulfonyl)-4
      methylvalerohydrazide (Ro 32-7315), is a potent, orally active inhibitor of the
      TNF-alpha convertase (TACE), an enzyme responsible for proteolytic cleavage of
      the membrane bound precursor, pro-TNF-alpha. Ro 32-7315 inhibited a recombinant
      form of TACE (IC(50) = 5.2 nM) with selectivity over related matrix
      metalloproteinases. In a cellular assay system, THP-1 cell line, and in human and
      rat whole blood, Ro 32-7315 significantly reduced lipopolysaccharide (LPS)
      induced TNF-alpha release with IC(50) values of 350 +/- 14 nM (n = 5), 2.4 +/-
      0.5 microM (n = 5), and 110 +/- 18 nM (n = 5), respectively. Oral administration
      of Ro 32-7315 to Wistar rats caused a dose-dependent inhibition of LPS-induced
      release of systemic TNF-alpha with an ED(50) of 25 mg/kg. Treatment (days 0-14)
      of Allen and Hamburys hooded rats with Ro 32-7315 (2.5, 5, 10, and 20 mg/kg,
      i.p., twice daily) significantly reduced adjuvant-induced secondary paw swelling
      (42, 71, 83, and 93%, respectively) as compared with the vehicle group. In the Ro
      32-7315-treated group, the reduced paw swelling was associated with improved
      lesion score and joint mobility. Furthermore, in a placebo-controlled, single
      dose study, Ro 32-7315 given orally (450 mg) significantly suppressed ex vivo,
      LPS-induced TNF-alpha release in the whole-blood samples taken from healthy male
      and female volunteers (mean inhibition of 42% over a 4-h duration, n = 6). These
      data collectively support the potential use of such a compound for the oral
      treatment of inflammatory disorders.

PMID- 12065743
TI  - Presynaptic muscarinic M(2)-receptor-mediated inhibition of N-type Ca(2+)
      channels in cultured sphenopalatine ganglion: direct evidence for acetylcholine
      inhibition of cerebral nitrergic neurogenic vasodilation.
AB  - Results of previous pharmacological studies suggested that presynaptic muscarinic
      M(2) receptors on cerebral perivascular nitric oxidergic (nitrergic) nerves
      mediated inhibition of nitric oxide release from these nerves. The inhibition was
      thought to be primarily attributable to a decreased Ca(2+) influx through N-type
      Ca(2+) channels on nitrergic nerves, but direct evidence supporting this
      hypothesis was not presented. In the present study, we used cultured rat
      sphenopalatine ganglion (SPG), a major source of nitrergic nerves to cerebral
      blood vessels, to investigate the role of muscarinic M(2) receptors in modulating
      voltage-dependent Ca(2+) channels. SPG neuronal soma and dendrites were
      immunoreactive for both N-type Ca(2+) channels and muscarinic M(2) receptors,
      indicating that muscarinic M(2) receptors were colocalized with N-type Ca(2+)
      channels. Using the whole-cell voltage-clamp technique, we found that voltage
      dependent Ca(2+) currents in cultured SPG were largely blocked by omega
      conotoxin, an N-type calcium channel antagonist, but were not affected by
      nifedipine, an L-type calcium antagonist. The Ca(2+) current was inhibited by
      acetylcholine (ACh) and arecaidine but-2-ynyl ester tosylate (ABET), a
      preferential muscarinic M(2)-receptor agonist, in a concentration-dependent
      manner. The inhibition was reversed by atropine and methoctramine (a muscarinic
      M(2)-receptor antagonist), but was not affected by muscarinic M(1)-, M(3)-, or
      M(4)-receptor antagonists. Consistent with this, preferential muscarinic M(1)
      receptor agonists McN-A-343 and oxotremorine did not affect the Ca(2+) current.
      Furthermore, pretreatment with pertussis toxin and guanosine 5'-O-(3
      thio)triphosphate prevented ACh and ABET inhibition of Ca(2+) currents. These
      results are consistent with pharmacological findings in the pig basilar arteries
      and provide direct evidence supporting our hypothesis that M(2)-receptor-mediated
      inhibition of cerebral nitrergic neurogenic vasodilation is due to a G(i)-protein
      mediated suppression of Ca(2+) influx via voltage-dependent N-type Ca(2+)
      channels on perivascular nerves.

PMID- 12065745
TI  - Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF
      2.
AB  - To identify genetic determinants of hypoxic cell death, we screened for hypoxia
      resistant (Hyp) mutants in Caenorhabditis elegans and found that specific
      reduction-of-function (rf) mutants of daf-2, an insulin/insulinlike growth factor
      (IGF) receptor (INR) homolog gene, were profoundly Hyp. The hypoxia resistance
      was acutely inducible just before hypoxic exposure and was mediated through an
      AKT-1/PDK-1/forkhead transcription factor pathway overlapping with but distinct
      from signaling pathways regulating life-span and stress resistance. Selective
      neuronal and muscle expression of daf-2(+) restored hypoxic death, and daf-2(rf)
      prevented hypoxia-induced muscle and neuronal cell death, which demonstrates a
      potential for INR modulation in prophylaxis against hypoxic injury of neurons and
      myocytes.

PMID- 12065746
TI  - Biallelic inactivation of BRCA2 in Fanconi anemia.
AB  - Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder
      characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes
      have been cloned, but the gene or genes corresponding to FA subtypes B and D1
      remain unidentified. Here we show that cell lines derived from FA-B and FA-D1
      patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins.
      Functional complementation of FA-D1 fibroblasts with wild-type BRCA2
      complementary DNA restores MMC resistance. Our results link the six cloned FA
      genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in
      this pathway may result in cancer risks similar to those observed in families
      with BRCA1 or BRCA2 mutations.

PMID- 12065747
TI  - Biomedicine. D-Day for BRCA2.

PMID- 12065748
TI  - Functional characterization of coding polymorphisms in the human MDR1 gene using
      a vaccinia virus expression system.
AB  - The human MDR1-encoded transporter is a 170-kDa plasma membrane glycoprotein [P
      glycoprotein (P-gp)] capable of binding and energy-dependent extrusion of
      structurally diverse organic compounds and drugs. P-gp seems to play a
      significant role in uptake, distribution, and excretion of many different drugs.
      To determine whether common polymorphic forms of P-gp are likely to alter
      function of P-gp, we characterized five known MDR1 coding polymorphisms (N21D,
      F103L, S400N, A893S, and A998T) using a vaccinia virus-based transient expression
      system. Cell surface expression of wild-type P-gp was time-dependent over a time
      course of 5.5 to 34.5 h; highest expression was obtained by 22 to 26.5 h after
      infection/transfection, indicating that a semiquantitative assay for P-gp
      expression levels was possible. HeLa cells stained with the P-gp specific
      monoclonal antibodies MRK-16 and Western blots probed with C219 revealed similar
      cell surface expression for the polymorphisms and for wild-type protein. Time
      dependent P-gp pump function maximal at 22 h after infection/transfection was
      demonstrated for the following MDR1 fluorescence substrates: 4,4-difluoro-5,7
      dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoic acid, succinimidyl ester
      (bodipy-FL)-verapamil, bodipy-FL-vinblastine, calcein-AM, bodipy-FL-prazosin,
      bisantrene, and bodipy-FL-forskolin, but not for daunorubicin. Transport studies
      of all tested substrates indicated that the substrate specificity of the pump was
      not substantially affected by any of the tested polymorphisms. Cell surface
      expression and function of double mutants including the more common polymorphisms
      (N21D-S400N, N21D-A893S, and S400N-A893S) showed no differences from wild-type.
      These results demonstrate that the common MDR1 coding polymorphisms result in P
      gps with a cell surface distribution and function similar to wild-type P-gp.

PMID- 12065749
TI  - Isolation, characterization and differential gene expression of multispecific
      organic anion transporter 2 in mice.
AB  - We isolated cDNA encoding a multispecific organic anion transporter 2 (OAT2) from
      the mouse kidney cDNA library. Isolated mouse OAT2 (mOAT2) consisted of 1623 base
      pairs that encoded a 540-amino acid residue protein with 12 putative membrane
      spanning domains, and the amino acid sequence was 87% identical to that of rat
      OAT2 (rOAT2). The gene coding for mOAT2, Slc22a7, is found on chromosome 17C.
      Northern blot analysis revealed that the mOAT2 mRNA is abundantly expressed in
      the male mouse kidney, whereas it was predominantly expressed in both the liver
      and kidney of female mice. When expressed in Xenopus laevis oocytes, mOAT2
      mediated the high affinity transport of glutarate (K(m) = 15.8 +/- 3.2 microM)
      and prostaglandin E2 (K(m) = 5.2 +/- 0.5 nM) in a sodium-independent manner.
      mOAT2-expressing oocytes also mediated the uptake of alpha-ketoglutarate,
      glutarate, prostaglandin E2, p-aminohippuric acid, methotrexate, ochratoxin A,
      valproate, and allopurinol. However, we did not observe mOAT2-mediated uptake of
      salicylate. A wide range of structurally unrelated organic anions inhibited mOAT2
      mediated glutarate uptake especially erythromycin, a potent inhibitor. These
      results indicate that isolated mOAT2 is a multispecific organic anion transporter
      having some differences in substrate specificity compared with rOAT2. In
      addition, we found that there exists a sex- and species-related differential gene
      expression of the OAT2 isoform.

PMID- 12065750
TI  - Design, synthesis and pharmacological evaluation of 5-hydroxytryptamine(1a)
      receptor ligands to explore the three-dimensional structure of the receptor.
AB  - In this work, we evaluate the structural differences of transmembrane helix 3 in
      rhodopsin and the 5-hydroxytryptamine 1A (5-HT1A) receptor caused by their
      different amino acid sequence. Molecular dynamics simulations of helix 3 in the 5
      HT1A receptor tends to bend toward helix 5, in sharp contrast to helix 3 in
      rhodopsin, which is properly located within the position observed in the crystal
      structure. The relocation of the central helix 3 in the helical bundle
      facilitates the experimentally derived interactions between the neurotransmitters
      and the Asp residue in helix 3 and the Ser/Thr residues in helix 5. The different
      amino acid sequence that forms helix 3 in rhodopsin (basically the conserved
      Gly(3.36)Glu(3.37) motif in the opsin family) and the 5-HT1A receptor (the
      conserved Cys(3.36)Thr(3.37) motif in the neurotransmitter family) produces these
      structural divergences. These structural differences were experimentally checked
      by designing and testing ligands that contain comparable functional groups but at
      different interatomic distance. We have estimated the position of helix 3
      relative to the other helices by systematically changing the distance between the
      functional groups of the ligands (1 and 2) that interact with the residues in the
      receptor. Thus, ligand 1 optimally interacts with a model of the 5-HT1A receptor
      that matches rhodopsin template, whereas ligand 2 optimally interacts with a
      model that possesses the proposed conformation of helix 3. The lack of affinity
      of 1 (K(i) > 10,000 nM) and the high affinity of 2 (K(i) = 24 nM) for the 5-HT1A
      receptor binding sites, provide experimental support to the proposed structural
      divergences of helix 3 between the 5-HT1A receptor and rhodopsin.

PMID- 12065752
TI  - NK1 receptor fused to beta-arrestin displays a single-component, high-affinity
      molecular phenotype.
AB  - Arrestins are cytosolic proteins that, upon stimulation of seven transmembrane
      (7TM) receptors, terminate signaling by binding to the receptor, displacing the G
      protein and targeting the receptor to clathrin-coated pits. Fusion of beta
      arrestin1 to the C-terminal end of the neurokinin NK1 receptor resulted in a
      chimeric protein that was expressed to some extent on the cell surface but also
      accumulated in transferrin-labeled recycling endosomes independently of agonist
      stimulation. As expected, the fusion protein was almost totally silenced with
      respect to agonist-induced signaling through the normal Gq/G11 and Gs pathways.
      The NK1-beta-arrestin1 fusion construct bound nonpeptide antagonists with
      increased affinity but surprisingly also bound two types of agonists, substance P
      and neurokinin A, with high, normal affinity. In the wild-type NK1 receptor,
      neurokinin A (NKA) competes for binding against substance P and especially
      against antagonists with up to 1000-fold lower apparent affinity than determined
      in functional assays and in homologous binding assays. When the NK1 receptor was
      closely fused to G proteins, this phenomenon was eliminated among agonists, but
      the agonists still competed with low affinity against antagonists. In contrast,
      in the NK1-beta-arrestin1 fusion protein, all ligands bound with similar affinity
      independent of the choice of radioligand and with Hill coefficients near unity.
      We conclude that the NK1 receptor in complex with arrestin is in a high-affinity,
      stable, agonist-binding form probably best suited to structural analysis and that
      the receptor can display binding properties that are nearly theoretically ideal
      when it is forced to complex with only a single intracellular protein partner.

PMID- 12065751
TI  - Inhibition of the mitochondrial permeability transition by the
      nonimmunosuppressive cyclosporin derivative NIM811.
AB  - Cyclosporin A (CsA) shows cytoprotective properties in many cellular and in vivo
      models that may depend on interference of the interaction of cyclophilin A with
      calcineurin or of cyclophilin D with the mitochondrial permeability transition
      (PT) pore. The nonimmunosuppressive cyclosporin derivative N-methyl-4-valine
      cyclosporin (PKF220-384) inhibits the mitochondrial permeability transition (MPT)
      like CsA but without calcineurin inactivation. PKF220-384 has been used to
      discriminate between PT pore- and calcineurin mediated effects but is no longer
      available. Here, we evaluated the effects of another nonimmunosuppressive
      cyclosporin derivative, N-methyl-4-isoleucine-cyclosporin (NIM811) on the MPT.
      Using two newly developed microtiter plate assays, one measuring mitochondrial
      swelling from absorbance and the other measuring mitochondrial membrane potential
      from changes in safranin fluorescence, we show that NIM811 blocks the MPT induced
      by calcium and inorganic phosphate, alone or in combination with the dopaminergic
      neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, the complex I inhibitor
      rotenone, and the prooxidant t-butylhydroperoxide. NIM811 was equipotent to CsA
      and half as potent as PKF220-384. Additionally, we show that NIM811 blocks cell
      killing and prevents in situ mitochondrial inner membrane permeabilization and
      depolarization during tumor necrosis factor-alpha-induced apoptosis to cultured
      rat hepatocytes. NIM811 inhibition of apoptosis was equipotent with CsA except at
      higher concentrations: CsA lost efficacy but NIM 811 did not. We conclude that
      NIM811 is a useful alternative to PKF220-384 to investigate the role of the
      mitochondrial permeability transition in apoptotic and necrotic cell death.

PMID- 12065753
TI  - Molecular modeling and site-specific mutagenesis of the histamine-binding site of
      the histamine H4 receptor.
AB  - The histamine H4 receptor is a novel G-protein-coupled receptor with a unique
      pharmacological profile. The distribution of H4 mRNA suggests that it may play a
      role in the regulation of immune function, particularly with respect to allergy
      and asthma. To define the histamine-binding site of this receptor, molecular
      modeling and site-directed mutagenesis were used to predict and alter amino acids
      residing in the histamine-binding pocket. The effects of these alterations on
      histamine binding and receptor activation were then assessed. Our results
      indicate that Asp94 (3.32) in transmembrane region (TM) 3 and Glu182 (5.46) in
      TM5 are critically involved in histamine binding. Asp94 probably serves as a
      counter-anion to the cationic amino group of histamine, whereas Glu182 (5.46)
      interacts with the N(tau) nitrogen atom of the histamine imidazole ring via an
      ion pair. In contrast, Thr178 (5.42) and Ser179 (5.43) in TM5 are not
      significantly involved in either histamine binding or receptor activation. These
      results resemble those for the analogous residues in the H1 histamine receptor
      but contrast with findings regarding the H2 histamine receptor. Our results also
      demonstrate that Asn147 (4.57) in TM4 and Ser320 (6.52) in TM6 play a role in
      receptor activation but are not involved in histamine binding. Taken together,
      these data indicate that although histamine seems to bind to the H4 receptor in a
      fashion similar to that predicted for the other histamine receptor subtypes,
      there are also important differences that can probably be exploited for the
      discovery of novel H4-selective compounds.

PMID- 12065754
TI  - Novel tarantula toxins for subtypes of voltage-dependent potassium channels in
      the Kv2 and Kv4 subfamilies.
AB  - Three novel peptides with the ability to inhibit voltage-dependent potassium
      channels in the shab (Kv2) and shal (Kv4) subfamilies were identified from the
      venom of the African tarantulas Stromatopelma calceata (ScTx1) and Heteroscodra
      maculata (HmTx1, HmTx2). The three toxins are 34- to 38-amino acid peptides that
      belong to the structural family of inhibitor cystine knot spider peptides
      reticulated by three disulfide bridges. Electrophysiological recordings in COS
      cells show that these toxins act as gating modifier of voltage-dependent K+
      channels. ScTx1 is the first high-affinity inhibitor of the Kv2.2 channel subtype
      (IC50, 21.4 nM) to be described. ScTx1 also inhibits the Kv2.1 channels, with an
      IC50 of 12.7 nM, and Kv2.1/Kv9.3 heteromultimers that have been proposed to be
      involved in O2 sensing in pulmonary artery myocytes. In addition, it is the most
      effective inhibitor of Kv4.2 channels described thus far, with an IC50 of 1.2 nM.
      HmTx toxins share sequence similarities with both the potassium channel blocker
      toxins (HmTx1) and the calcium channel blocker toxin omega-GsTx SIA (HmTx2). They
      inhibit potassium current associated with Kv2 subtypes in the 100 to 300 nM
      concentration range. HmTx2 seems to be a specific inhibitor of Kv2 channels,
      whereas HmTx1 also inhibits Kv4 channels, including Kv4.1, with the same potency.
      HmTx1 is the first described peptide effector of the Kv4.1 subtype. Those novel
      toxins are new tools for the investigation of the physiological role of the
      different potassium channel subunits in cellular physiology.

PMID- 12065755
TI  - Inhibition of transforming growth factor (TGF)-beta1-induced extracellular matrix
      with a novel inhibitor of the TGF-beta type I receptor kinase activity: SB
      431542.
AB  - Transforming growth factor beta1 (TGF-beta1) is a potent fibrotic factor
      responsible for the synthesis of extracellular matrix. TGF-beta1 acts through the
      TGF-beta type I and type II receptors to activate intracellular mediators, such
      as Smad proteins, the p38 mitogen-activated protein kinase (MAPK), and the
      extracellular signal-regulated kinase pathway. We expressed the kinase domain of
      the TGF-beta type I receptor [activin receptor-like kinase (ALK)5] and the
      substrate, Smad3, and determined that SB-431542 is a selective inhibitor of Smad3
      phosphorylation with an IC50 of 94 nM. It inhibited TGF-beta1-induced nuclear
      Smad3 localization. The p38 mitogen-activated protein kinase inhibitors SB-203580
      and SB-202190 also inhibit phosphorylation of Smad3 by ALK5 with IC50 values of 6
      and 3 microM, respectively. This suggests that these p38 MAPK inhibitors must be
      used at concentrations of less than 10 microM to selectively address p38 MAPK
      mechanisms. However, the p38 MAPK inhibitor SB-242235 did not inhibit ALK5. To
      evaluate the relative contribution of Smad signaling and p38 MAPK signaling in
      TGF-beta1-induced matrix production, the effect of SB-431542 was compared with
      that of SB-242235 in renal epithelial carcinoma A498 cells. All compounds
      inhibited TGF-beta1-induced fibronectin (FN) mRNA, indicating that FN synthesis
      is mediated in part via the p38 MAPK pathway. In contrast, SB-431542, but not the
      selective p38 MAPK inhibitor SB-242235, inhibited TGF-beta1-induced collagen
      Ialpha1 (col Ialpha1). These data indicate that some matrix markers that are
      stimulated by TGF-beta1 are mediated via the p38 MAPK pathway (i.e., FN), whereas
      others seem to be activated via ALK5 signaling independent of the p38 MAPK
      pathway (i.e., col Ialpha1).

PMID- 12065757
TI  - Molecular mechanisms for the activation of voltage-independent Ca2+ channels by
      endothelin-1 in chinese hamster ovary cells stably expressing human endothelin(A)
      receptors.
AB  - We demonstrated recently that in Chinese hamster ovary cells stably expressing
      human recombinant endothelin(A) receptors (CHO-ET(A)R), endothelin-1 (ET-1)
      activates two types of Ca2+-permeable nonselective cation channels (designated
      NSCC-1 and NSCC-2) and a store-operated Ca2+ channel (SOCC), which can be
      distinguished by Ca(2+) channel blockers such as 1-[beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imidazole hydrochloride (SK&F
      96365) and (R,S)-(3,4-dihydro-6,7-dimethoxy-isochinolin-1-yl)-2-phenyl-N,N-di[2
      (2,3,4-trimethoxyphenyl)ethyl]acetamid mesylate (LOE 908). We also reported that
      CHO-ET(A)R couples with G12 in addition to G(q) and G(s). The purpose of the
      present study was to identify the G proteins involved in the activation of these
      Ca2+ channels by ET-1, using mutated ET(A)Rs with coupling to either G(q) or
      G(s)/G12 (designated ET(A)RDelta385 and SerET(A)R, respectively) and a dominant
      negative mutant of G12 (G12G228A). ET(A)RDelta385 is truncated immediately
      downstream of Cys385 in the C terminus as palmitoylation sites, whereas SerET(A)R
      is unpalmitoylated because of substitution of all the cysteine residues to serine
      (Cys383Cys385-388 --> Ser383Ser385-388). In CHO-ET(A)RDelta385, stimulation with
      ET-1 activated only SOCC. In CHO-SerET(A)R or CHO-ET(A)R pretreated with U73122,
      an inhibitor of phospholipase C (PLC), ET-1 activated only NSCC-1. Dibutyryl cAMP
      alone did not activate any Ca2+ channels in the resting and ET-1-stimulated CHO
      SerET(A)R. Microinjection of G12G228A abolished the activation of NSCC-1 and NSCC
      2 in CHO-ET(A)R and that of NSCC-1 in CHO-SerET(A)R. These results indicate that
      ET(A)R activates three types of Ca2+ channels via different G protein-related
      pathways. NSCC-1 is activated via a G12-dependent pathway, NSCC-2 via G(q)/PLC-
      and G12-dependent pathways, and SOCC via a G(q)/PLC-dependent pathway.

PMID- 12065756
TI  - SB-431542 is a potent and specific inhibitor of transforming growth factor-beta
      superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and
      ALK7.
AB  - Small molecule inhibitors have proven extremely useful for investigating signal
      transduction pathways and have the potential for development into therapeutics
      for inhibiting signal transduction pathways whose activities contribute to human
      diseases. Transforming growth factor beta (TGF-beta) is a member of a large
      family of pleiotropic cytokines that are involved in many biological processes,
      including growth control, differentiation, migration, cell survival, adhesion,
      and specification of developmental fate, in both normal and diseased states. TGF
      beta superfamily members signal through a receptor complex comprising a type II
      and type I receptor, both serine/threonine kinases. Here, we characterize a small
      molecule inhibitor (SB-431542) that was identified as an inhibitor of activin
      receptor-like kinase (ALK)5 (the TGF-beta type I receptor). We demonstrate that
      it inhibits ALK5 and also the activin type I receptor ALK4 and the nodal type I
      receptor ALK7, which are very highly related to ALK5 in their kinase domains. It
      has no effect on the other, more divergent ALK family members that recognize bone
      morphogenetic proteins (BMPs). Consistent with this, we demonstrate that SB
      431542 is a selective inhibitor of endogenous activin and TGF-beta signaling but
      has no effect on BMP signaling. To demonstrate the specificity of SB-431542, we
      tested its effect on several other signal transduction pathways whose activities
      depend on the concerted activation of multiple kinases. SB-431542 has no effect
      on components of the ERK, JNK, or p38 MAP kinase pathways or on components of the
      signaling pathways activated in response to serum.

PMID- 12065758
TI  - Selective allosteric enhancement of agonist binding and function at human A3
      adenosine receptors by a series of imidazoquinoline derivatives.
AB  - We have identified a series of 1H-imidazo-[4,5-c]quinolines as selective
      allosteric enhancers of human A3 adenosine receptors. Several of these compounds
      potentiated both the potency and maximal efficacy of agonist-induced responses
      and selectively decreased the dissociation of the agonist N6-(4-amino-3
      [125I]iodobenzyl)-5'-N-methylcarboxamidoadenosine from human A3 adenosine
      receptors. There was no effect on the dissociation of the antagonist [3H]8-ethyl
      4-methyl-2-phenyl-(8R)-4,5,7,8-tetrahydro-1H-imidazo[2.1-i]purin-5-one (PSB-11)
      from the A3 receptors, as well as [3H]N6-[(R)-phenylisopropyl]adenosine from rat
      brain A1 receptors and [3H]2-[p-(2-carboxyethyl)phenyl-ethylamino]-5'-N
      ethylcarboxamidoadenosine from rat striatal A2A receptors, suggesting the
      selective enhancement of agonist binding at A3 receptors. The analogs were tested
      as antagonists of competitive binding at human A3 receptors, and K(i) values
      ranging from 120 nM to 101 microM were observed; as for many allosteric
      modulators of G protein-coupled receptors, an orthosteric effect was also
      present. The most promising leads from the present set of analogs seem to be the
      2-cyclopentyl-1H-imidazo[4,5-c]quinoline derivatives, of which the 4-phenylamino
      analog DU124183 had the most favorable degree of allosteric modulation versus
      receptor antagonism. The inhibition of forskolin-stimulated cyclic AMP
      accumulation in intact cells that express human A3 receptors was employed as a
      functional index of A3 receptor activation. The enhancer DU124183 caused a marked
      leftward shift of the concentration-response curve of the A3 receptor agonists in
      the presence of antagonist and, surprisingly, a potentiation of the maximum
      agonist efficacy by approximately 30%. Thus, we have identified a novel
      structural lead for developing allosteric enhancers of A3 adenosine receptors;
      such enhancers may be useful for treating brain ischemia and other hypoxic
      conditions.

PMID- 12065759
TI  - Aurintricarboxylic acid protects against cell death caused by lipopolysaccharide
      in macrophages by decreasing inducible nitric-oxide synthase induction via
      IkappaB kinase, extracellular signal-regulated kinase, and p38 mitogen-activated
      protein kinase inhibition.
AB  - To elucidate the mechanisms involved in cell protection by aurintricarboxylic
      acid (ATA), an endonuclease inhibitor, high nitric oxide (NO)-induced macrophage
      apoptosis was studied. In RAW 264.7 macrophages, a high level of NO production
      accompanied by cell apoptosis was apparent with lipopolysaccharide (LPS)
      treatment. Direct NO donor sodium nitroprusside (SNP) also dramatically induced
      cell death, with an EC(50) of 1 mM. Coincubation of ATA (1-500 microM) in LPS
      stimulated RAW 264.7 cells resulted in a striking reduction of NO production and
      cell apoptosis, whereas only a partial cell protection was achieved in response
      to SNP. This suggests that abrogation of inducible nitric-oxide synthase (iNOS)
      dependent NO production might contribute to ATA protection of LPS-treated cells.
      Immunoblotting and reverse transcription-polymerase chain reaction analysis
      revealed that ATA down-regulated iNOS protein through transcriptional inhibition
      of iNOS gene expression but was unrelated to iNOS protein stability. ATA not only
      inhibited nuclear factor-kappaB (NF-kappaB) activation through impairment of the
      targeting and degradation of IkappaBs but also reduced LPS-induced activator
      protein-1 (AP-1) activation. These actions of ATA were not caused by the
      influence on LPS binding to macrophage membrane. Kinase assays indicated that ATA
      inhibited IkappaB kinase (IKK), extracellular signal-regulated kinase (ERK), and
      p38 mitogen-activated protein kinase (MAPK) activity both in vivo and in vitro,
      suggesting a direct interaction between ATA and these signaling molecules. Taken
      together, these results provide novel action targets of ATA and indicate that ATA
      protection of macrophages from LPS-mediated cell death is primarily the result of
      its inhibition of NO production, which closely relates to the inactivation of NF
      kappaB and AP-1 and inhibition of IKK, ERK and p38 MAPK.

PMID- 12065760
TI  - The effect of thiopurine methyltransferase expression on sensitivity to
      thiopurine drugs.
AB  - Although the thiopurine drugs 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG)
      are well established agents for the treatment of leukemia, controversies remain
      regarding their main mode of action. Previous evidence has suggested that
      although 6-TG exerts a cytotoxic effect through incorporation of 6-thioguanine
      nucleotides into newly synthesized DNA (DNA-TGN), an important component of the
      mode of action of 6-MP is inhibition of purine de novo synthesis (PDNS) through
      the production of S-methyl-thioinosine 5'-monophosphate (MeTIMP), not formed in
      cells exposed to 6-TG. We have shown that thiopurine methyltransferase (TPMT)
      modulates this effect. By transfection of the human TPMT gene using an inducible
      system to produce a 3.8-fold increase in TPMT activity in the ecdysone receptor
      293 embryonic kidney cell line, we demonstrated a 4.4-fold increase in
      sensitivity to 6-MP. This was associated with a rise in intracellular levels of
      MeTIMP but a decrease in levels of DNA-TGN. In contrast, induction of TPMT
      produced a 1.6-fold decrease in sensitivity to 6-TG, a decrease in levels of DNA
      TGN, and an increase in levels of methylated thioguanosine monophosphate.
      Exposure of cells to equitoxic doses of drug showed similar incorporation of DNA
      TGN for 6-TG but for 6-MP significantly reduced DNA-TGN in TPMT-induced compared
      with uninduced cells. For equitoxic doses of 6-MP, equivalent levels of MeTIMP
      correlated with equivalent amounts of PDNS. These observations suggest that
      intracellular TGN levels do not give an accurate reflection of cytotoxic
      potential in patients treated with 6-MP, because different levels of DNA-TGN may
      be associated with equitoxic effects.

PMID- 12065761
TI  - Alteration of the heme prosthetic group of neuronal nitric-oxide synthase during
      inactivation by N(G)-amino-L-arginine in vitro and in vivo.
AB  - It is established that N(G)-amino-L-arginine (NAA) is a metabolism-based
      inactivator of all three major nitric-oxide synthase (NOS) isoforms. The
      mechanism by which this inactivation occurs, however, is not well understood. In
      the current study, we discovered that inactivation of the neuronal isoform of NOS
      (nNOS) by NAA in vitro results in covalent alteration of the heme prosthetic
      group, in part, to products that contain an intact porphyrin ring and are either
      dissociable from or irreversibly bound to the protein. The alteration of the heme
      is concomitant with the loss of nNOS activity. Studies with nNOS containing a 14C
      labeled prosthetic heme moiety indicate that the major dissociable product and
      the irreversibly bound heme adduct account for 21 and 28%, respectively, of the
      heme that is altered. Mass spectral analysis of the major dissociable product
      gave a molecular ion of m/z 775.3 that is consistent with the mass of an adduct
      of heme and NAA minus a hydrazine group. Peptide mapping of the irreversibly
      bound heme adduct indicates that the heme is bound to a residue in the oxygenase
      domain of nNOS. We show for the first time that metabolism-based inactivation of
      nNOS occurs in vivo as highly similar heme products are formed. Because
      inactivation and alteration may trigger ubiquitination and proteasomal
      degradation of nNOS, NAA may be a useful biochemical tool for the study of these
      basic regulatory processes.

PMID- 12065762
TI  - Classic D1 dopamine receptor antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390) directly
      inhibits G protein-coupled inwardly rectifying potassium channels.
AB  - R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride (SCH23390) is a widely used, highly selective antagonist of D1
      dopamine receptors. While investigating the crosstalk between D1 and D3 dopamine
      receptor signaling pathways, we discovered that in addition to being a D1
      receptor antagonist, SCH23390 and related compounds inhibit G protein-coupled
      inwardly rectifying potassium (GIRK) channels. We present evidence that SCH23390
      blocks endogenous GIRK currents induced by either somatostatin or D3 dopamine
      receptors in AtT-20 cells (IC50, 268 nM). The inhibition is receptor-independent
      because constitutive GIRK currents in Chinese hamster ovary cells expressing only
      GIRK channels are also blocked by SCH23390. The inhibition of GIRK channels is
      somewhat selective because members of the closely related Kir2.0 family of
      inwardly rectifying potassium channels, as well as various endogenous cationic
      currents present in AtT-20 cells, are not affected. In addition, in current clamp
      recordings, SCH23390 can depolarize the membrane potential and induce AtT-20
      cells to fire action potentials, indicating potential physiological significance
      of the GIRK channel inhibition. To identify the chemical features that contribute
      to GIRK channel block, we tested several structurally related compounds
      [SKF38393, R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride (nor-methyl-SCH23390), and R-(+)-2,3,4,5-tetrahydro-8-iodo-3-methyl
      5-phenyl-1H-3-benzazepin-7-ol hydrochloride (iodo-SCH23390)], and our results
      indicate that the halide atom is critical for blocking GIRK channels. Taken
      together, our results suggest that SCH23390 and related compounds might provide
      the basis for designing novel GIRK channel-selective blockers. Perhaps more
      importantly, some studies that have exclusively used SCH23390 to probe D1
      receptor function or as a diagnostic of D1 receptor involvement may need to be
      reevaluated in light of these results.

PMID- 12065763
TI  - Molecular determinants of intracellular pH modulation of human Kv1.4 N-type
      inactivation.
AB  - A-type K+ currents serve important functions in neural and cardiac physiology.
      The human A-type Kv1.4 channel (hKv1.4) shows fast N-type inactivation when
      expressed in Xenopus laevis oocytes. We found that intracellular pH (pH(i))
      regulated the macroscopic inactivation time constant (tau) and current amplitude
      (I(peak)), producing a 2-fold change with each pH unit change in the
      physiologically relevant range of 8.0 to 6.0. These effects of pH(i) were
      completely abolished by a large deletion in the hKv1.4 N terminus. Site-directed
      mutagenesis identified a histidine (H16) in the inactivation ball domain as a
      critical H+ titratable site mediating the pH effects on N-type inactivation
      between pH 7.0 and 9.0. Substituting this histidine with arginine not only
      accelerated the time course of macroscopic channel inactivation but also
      eliminated the H+ effects on hKv1.4. In addition, a glutamic acid (E2) in the
      ball domain constitutes another H+ titratable site that mediates the pH effects
      in the more acidic pH range of 5.0 to 7.0. These results suggest that N-type
      inactivation in hKv1.4 is regulated by pH(i) in the physiologic range through
      ionization of specific amino acid residues in the ball domain. Such pH(i) effects
      may represent an important fundamental mechanism for physiological regulation of
      excitable tissue function.

PMID- 12065764
TI  - Integrated channel plasticity contributes to alcohol tolerance in
      neurohypophysial terminals.
AB  - Short-term ethanol challenge results in the reduction of peptide hormone release
      from the rat neurohypophysis. However, rats that have been maintained on an
      ethanol-containing diet for 3 to 4 weeks exhibit tolerance to this effect.
      Mechanistic underpinnings of this tolerance were probed by examining four ion
      channel conductances critical for neurohormone release. The voltage-gated L-type
      calcium channel and the functionally linked calcium-activated BK channel
      represent a functional dyad. Although these channels show opposite drug responses
      in the naive terminal (i.e., the L-type Ca2+ channel is inhibited whereas the BK
      channel is potentiated), the effect of long-term alcohol exposure is to decrease
      sensitivity to the short-term administration of drug in both instances. In
      addition to the shift in sensitivity, current density increased for the L-type
      Ca2+ current and decreased for the BK current, consistent with a compensatory
      change. Sensitivity to alcohol was also altered for two other channel types
      studied. Inhibition of the voltage-gated transient Ca2+ current was lessened
      after long-term treatment. I(A,) which is not sensitive to the drug at clinically
      relevant concentrations in terminals from the naive rat, acquires sensitivity
      after long-term exposure, representing a potentially novel type of tolerance.
      However, neither the transient Ca2+ current nor I(A) shows a change in current
      density, demonstrating the selectivity of this aspect of tolerance. Overall,
      these results demonstrate that channel plasticity can explain at least a portion
      of the behavioral tolerance resulting from changes in sensitivity of peptide
      hormone release. Furthermore, they suggest that an understanding of tolerance
      requires the examination of dynamically coupled channel populations.

PMID- 12065765
TI  - Activation of the antitumor agent aminoflavone (NSC 686288) is mediated by
      induction of tumor cell cytochrome P450 1A1/1A2.
AB  - The present studies were performed to elucidate the mechanism of cytotoxicity of
      the aminoflavone analog (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1
      benzopyran-4-one (AF; NSC 686288), a novel flavone with potent in vitro and in
      vivo antiproliferative activity against a number of human tumor cell lines and
      with a unique pattern of antiproliferative activity in the National Cancer
      Institute tumor cell line screen. AF was extensively metabolized by cytochrome
      P450 (P450) 1A1 and 1A2 to several metabolites, one of which was identified by
      mass spectrometry as a potentially reactive hydroxylamine. Radiolabeled AF was
      converted by rat and human microsomes, by recombinant CYP1A1 and CYP1A2, and by
      sensitive human tumor cell lines to species that covalently bound macromolecules.
      Treatment of sensitive human MCF7 cells with AF resulted in increased CYP1A1 mRNA
      and CYP1A1/1A2 protein followed by covalent binding of an AF metabolite to DNA,
      phosphorylation and stabilization of p53, and increased expression of the p53
      transcriptional target p21. Covalent binding of the AF metabolite was increased
      by pretreatment with the CYP1A inducer 3-methylcholanthrene and decreased by
      coincubation with the CYP1A inhibitor alpha-naphthoflavone. In contrast,
      induction of CYP1A1 and covalent binding of the AF metabolite did not occur in AF
      resistant M14-MEL cells. These observations suggest that AF is uniquely able to
      induce its own metabolic activation via CYP1A1/1A2 in duction to cytotoxic DNA
      damaging species directly in tumor cells. AF, and possibly other agents, may
      offer a treatment strategy for tumors responsive to CYP1A1/1A2 induction, such as
      breast, ovarian, and renal cancers.

PMID- 12065766
TI  - The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1alpha
      mediated activation of the UDP-glucuronosyltransferase 2B17 gene.
AB  - UDP glucuronosyltransferases (UGT) are expressed in a wide range of tissues in
      which their levels of expression and distribution are dependent on cell-type
      specific regulatory mechanisms. The presence of a hepatocyte nuclear factor (HNF)
      1 binding site in the proximal promoters of several UGT2B genes has been shown to
      contribute to their expression in liver cells and possibly other HNF1-containing
      cell types. In some of these UGT2B genes, a putative pre-B cell homeobox (Pbx)
      transcription factor binding site is found directly adjacent to the functional
      HNF1 site. To determine whether this putative Pbx site contributes to the
      regulation of UGT2B expression, we chose the UGT2B17 gene and investigated the
      capacity of its Pbx site to bind specific transcription factors and alter
      promoter activity. The UGT2B17 Pbx site matches a consensus Pbx site known to
      bind members of the Pbx, Hox, Meis, and Prep1 families of homeodomain-containing
      proteins and has previously been shown to bind nuclear proteins in DNaseI
      footprint assays. In this study, we used gel shift and functional assays to show
      that a Pbx2-Prep1 heterodimer can bind to the UGT2B17 Pbx site and interfere with
      the binding of HNF1alpha to its site adjacent to the Pbx site. This interaction
      of Pbx2-Prep1 and HNF1alpha results in down-regulation of HNF1alpha-mediated
      activation of the UGT2B17 promoter. Modulation of transcription by restricting
      the binding of transcriptional effectors to their target site is a novel role for
      Pbx2-Prep1 complexes.

PMID- 12065767
TI  - Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal
      midazolam metabolism.
AB  - We recently demonstrated that a variant allele of CYP3A5 (CYP3A5*3) confers low
      CYP3A5 expression as a result of improper mRNA splicing. In this study, we
      further evaluated the regulation of CYP3A5 in liver and jejunal mucosa from white
      donors. For all tissues, high levels of CYP3A5 protein were strongly concordant
      with the presence of a wild-type allele of the CYP3A5 gene (CYP3A5*1). CYP3A5
      represented greater than 50% of total CYP3A content in nearly all of the livers
      and jejuna that carried the CYP3A5*1 wild-type allele. Overall, CYP3A5 protein
      content accounted for 31% of the variability in hepatic midazolam hydroxylation
      activity. Improperly spliced mRNA (SV1-CYP3A5) was found only in tissues
      containing a CYP3A5*3 allele. Properly spliced CYP3A5 mRNA (wt-CYP3A5) was
      detected in all tissues, but the median wt-CYP3A5 mRNA was 4-fold higher in
      CYP3A5*1/*3 livers compared with CYP3A5*3/*3 livers. Differences in wt-CYP3A5 and
      CYP3A4 mRNA content explained 53 and 51% of the interliver variability in CYP3A5
      and CYP3A4 content, respectively. Hepatic CYP3A4 and CYP3A5 contents were not
      correlated when all livers were compared. However, for CYP3A5*1/*3 livers, levels
      of the two proteins were strongly correlated (r = 0.93) as were wt-CYP3A5 and
      CYP3A4 mRNA (r = 0.76). These findings suggest that CYP3A4 and CYP3A5 genes share
      a common regulatory pathway for constitutive expression, possibly involving
      conserved elements in the 5'-flanking region.

PMID- 12065768
TI  - The unique property of the CC chemokine regakine-1 to synergize with other plasma
      derived inflammatory mediators in neutrophil chemotaxis does not reside in its
      NH2-terminal structure.
AB  - The recently discovered CC chemokine, regakine-1, is constitutively present in
      bovine serum and synergizes with the CXC chemokine interleukin-8 (IL-8) to
      chemoattract neutrophils. Here we show that regakine-1 cooperates with the CXC
      chemokine receptor 2 ligand neutrophil activating protein-2 (NAP-2) and the
      anaphylatoxin C5a, two other mediators of inflammation present in the
      circulation. Neutrophil chemotaxis was 3-fold enhanced when regakine-1 (100
      ng/ml) and C5a (30 ng/ml) were combined at concentrations present in bovine or
      human plasma, respectively. This synergy was also observed when neutrophils were
      preincubated with regakine-1. Plasma chemokines such as NAP-2, beta
      thromboglobulin, and hemofiltrate CC-chemokine-1 did not affect C5a chemotactic
      activity. The capability of regakine-1 to synergize with C5a, NAP-2, or N-formyl
      methionyl-leucyl-phenylalanine (fMLP) was not observed for monocyte chemotactic
      protein-3 (MCP-3), another CC chemokine that weakly chemoattracts neutrophils.
      Regakine-1 also failed to cooperate with MCP-3 and macrophage inflammatory
      protein-1alpha in neutrophil chemotaxis. The receptor of regakine-1 is not known
      yet. Competition with labeled fMLP or C5a for binding to neutrophils or receptor
      transfected cell lines demonstrated that regakine-1 did not alter receptor
      recognition. The protein kinase inhibitors 2'-amino-3'-methoxyflavone (PD98059),
      wortmannin and staurosporin had no effect on the synergy between C5a and regakine
      1. Although NH2-terminal truncation affects the chemotactic potency of most
      chemokines, it did not affect the synergistic capacity of regakine-1 with C5a on
      neutrophils. These findings indicate that the constitutive plasma chemokine
      regakine-1 is a stable enhancer of the inflammatory response and that its
      blockade might be beneficial in acute and systemic inflammatory disorders.

PMID- 12065769
TI  - [125I]2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), a high
      affinity radioligand selective for I1 imidazoline receptors.
AB  - The I1 subtype of imidazoline receptors (I1R) is a plasma membrane protein that
      is involved in diverse physiological functions. Available radioligands used so
      far to characterize the I(1)R were able to bind with similar affinities to alpha2
      adrenergic receptors (alpha2-ARs) and to I1R. This feature was a major drawback
      for an adequate characterization of this receptor subtype. New imidazoline
      analogs were therefore synthesized and the present study describes one of these
      compounds, 2-(2-chloro-4-iodo-phenylamino)-5-methyl-pyrroline (LNP 911), which
      was of high affinity and selectivity for the I1R. LNP 911 was radioiodinated and
      its binding properties characterized in different membrane preparations.
      Saturation experiments with [125I]LNP 911 revealed a single high affinity binding
      site in PC-12 cell membranes (K(D) = 1.4 nM; B(max) = 398 fmol/mg protein) with
      low nonspecific binding. [125I]LNP 911 specific binding was inhibited by various
      imidazolines and analogs but was insensitive to guanosine-5'-O-(3
      thio)triphosphate. The rank order of potency of some competing ligands [LNP 911,
      PIC, rilmenidine, 4-chloro-2-(imidazolin-2-ylamino)-isoindoline (BDF 6143),
      lofexidine, and clonidine] was consistent with the definition of [125I]LNP 911
      binding sites as I1R. However, other high-affinity I1R ligands (moxonidine,
      efaroxan, and benazoline) exhibited low affinities for these binding sites in
      standard binding assays. In contrast, when [125I]LNP 911 was preincubated at 4
      degrees C, competition curves of moxonidine became biphasic. In this case,
      moxonidine exhibited similar high affinities on [125I]LNP 911 binding sites as on
      I1R defined with [125I]PIC. Moxonidine proved also able to accelerate the
      dissociation of [125I]LNP 911 from its binding sites. These results suggest the
      existence of an allosteric modulation at the level of the I1R, which seems to be
      corroborated by the dose-dependent enhancement by LNP 911 of the agonist effects
      on the adenylate cyclase pathway associated to I1R. Because [125I]LNP 911 was
      unable to bind to the I2 binding site and alpha2AR, our data indicate that
      [125I]LNP 911 is the first highly selective radioiodinated probe for I1R with a
      nanomolar affinity. This new tool should facilitate the molecular
      characterization of the I1 imidazoline receptor.

PMID- 12065770
TI  - Malignant peripheral nerve sheath tumors are t(X;18)-negative sarcomas. Molecular
      analysis of 25 cases occurring in neurofibromatosis type 1 patients, using two
      different RT-PCR-based methods of detection.
AB  - To verify the absence of the synovial sarcoma translocation t(X;18) (SYT-SSX) in
      malignant peripheral nerve sheath tumors, 34 tumor samples from 25
      neurofibromatosis type 1 patients were examined in two independent laboratories
      (Bordeaux, France, and Lausanne, Switzerland) using reverse transcriptase
      polymerase chain reaction (RT-PCR)-based techniques. RNA was extracted from
      paraffin blocks using standard methods, reverse transcribed, and conventional (in
      one laboratory) versus real-time (in the other laboratory) PCR performed. Twenty
      seven tumor samples from 19 patients were negative for the t(X;18) in both
      laboratories; six additional tumors that were t(X;18)-negative in one laboratory
      gave noninterpretable results in the other, due to lack of internal positive
      controls; one case was noninterpretable in both places. In conclusion, malignant
      peripheral nerve sheath tumors in neurofibromatosis type 1 patients do not bear
      the synovial sarcoma t(X;18) (SYT-SSX). Laboratories that use PCR-based
      techniques for diagnostic purposes would benefit from quality assurance programs.

PMID- 12065771
TI  - Heparanase: a key enzyme in invasion and metastasis of gastric carcinoma.
AB  - Previous reports have shown that the biochemical activity of heparanase is
      significantly correlated with the invasion and metastasis of malignant cells in
      vitro. Recently, it was found that the human heparanase gene was cloned and
      highly expressed in malignant cell lines and human solid malignant tumors. In the
      present study, we investigated the heparanase mRNA expression by using in situ
      hybridization in 116 paraffin-embedded tissues of primary gastric carcinomas. To
      explore its clinicopathologic significance, it was detected in the various steps
      of tumor progression and then compared with prognostic indicators. As a result,
      the heparanase expression was more prevalent in late-stage rather than early
      stage carcinomas (P <.0001) and was more frequent in tumors of large size (P
      =.0212). Expression also correlated with lymphatic (P =.0086) and venous (P
      =.0171) invasion and with negative prognostic factors such as lymph nodal (P
      <.0001) and distant (P =.0221) metastases. However, in a multivariate analysis,
      messenger RNA expression of heparanase was not an independent prognostic factor.
      It was concluded that heparanase might play an important role in the development
      of invasion and metastasis of the gastric cancer. It was indicated that patients
      with heparanase-positive gastric carcinoma would have a greater chance of
      metastasis with a poor prognosis.

PMID- 12065772
TI  - Mucinous and nonmucinous appendiceal adenocarcinomas: different
      clinicopathological features but similar genetic alterations.
AB  - The genetic alterations of appendiceal carcinomas have not been reported in
      detail. We studied the clinicopathological factors and genetic alterations
      including microsatellite instability, p53 overexpression, and mutations of the K
      ras proto-oncogene of 30 appendiceal adenocarcinomas, consisting of 23 mucinous
      and 7 nonmucinous carcinomas. Sixteen (70%) mucinous carcinomas presented with
      pseudomyxoma peritonei, but 6 of 7 (86%) nonmucinous carcinomas presented with
      appendicitis (P =.002). All carcinomas were microsatellite stable, and p53
      overexpression was present in only 1 of 30 (3%) carcinomas. K-ras mutation was
      present in 11 of 20 (55%) carcinomas, including 8 of 16 (50%) mucinous and 3 of 4
      (75%) nonmucinous carcinomas. The mean survival of patients with mucinous
      carcinomas was 26 +/- 19 months compared with 13 +/- 9 months for patients with
      nonmucinous carcinomas (P =.0002). Our findings suggest that mucinous and
      nonmucinous carcinomas of appendix have similar genetic alterations, but
      different clinical presentation and prognosis.

PMID- 12065773
TI  - Infrequent p53 gene mutations and lack of p53 protein expression in clear cell
      sarcoma of the kidney: immunohistochemical study and mutation analysis of p53 in
      renal tumors of unfavorable prognosis.
AB  - A high prevalence of p53 gene mutation and protein expression has been found in
      the anaplastic variant of Wilms' tumor (WT), known to be associated with poor
      outcome. However, there are very few studies of p53 alterations in the other two
      rare and highly malignant renal tumors in childhood, in other words, clear cell
      sarcoma of the kidney (CCSK) and malignant rhabdoid tumor of the kidney (MRTK).
      Overexpression of p53 protein has been detected in eight CCSKs in one study, and
      in two in another, yet no molecular correlation with p53 gene mutations has been
      carried out. Our study is the first molecular analysis concerning p53 in CCSK. We
      investigated eight cases of CCSK and one case of MRTK for p53 protein expression
      by immunohistochemical staining. All were analyzed for p53 mutations in the
      region of exons 4 to 8 by polymerase chain reaction-single-strand conformational
      polymorphism (PCR-SSCP) method and DNA sequencing analysis. By histological
      study, no CCSK showed anaplastic features. None expressed p53 protein, but two
      harbored p53 mutations. One was in exon 5, with a base pair insertion between
      codons 162 to 163 causing frameshift alteration in amino acid. Another was a
      silent CTC-->CTT transversion in codon 289 of exon 8. The case of MRTK did not
      show any alterations of p53 protein or gene. Our result indicates that p53
      alterations are infrequent in CCSK and do not seem to be primary genetic events
      in the pathogenesis of CCSK.

PMID- 12065774
TI  - Utilization of cytokeratins 7 and 20 does not differentiate between Barrett's
      esophagus and gastric cardiac intestinal metaplasia.
AB  - Long segment Barrett's esophagus (LSBE) is a recognized risk factor for the
      development of esophageal dysplasia and carcinoma. However, the risk of dysplasia
      arising within intestinal metaplasia below a normal-appearing Z-line (i.e., in
      native cardiac mucosa) is unknown. Regular endoscopic surveillance is required in
      patients with LSBE and is frequently performed in short segment BE (SSBE), but
      the need for surveillance in cardiac intestinal metaplasia (CIM) is unknown.
      Unfortunately IM arising in SSBE and immediately below a normal Z-line can be
      indistinguishable histologically on H&E stains. Previous reports suggest that the
      appearance of superficial CK20 immunohistochemical staining accompanied by
      intermediate and deep CK7 positivity is characteristic of BE, whereas CIM
      specimens show superficial and deep CK20 positivity and weak to absent CK7
      staining. We hypothesized that CK7/20 immunostaining of metaplastic biopsies from
      the esophagus and stomach would allow complete differentiation of these two
      entities when correlated with the endoscopic appearance. We undertook an
      evaluation of gastric and esophageal specimens to determine whether these
      characteristics were valid. Cases of both BE (long and short segment) and CIM, as
      well as cases of gastric cardiac biopsies lacking IM, were evaluated for CK7 and
      CK20 and correlated with the endoscopic appearance. We observed that, although
      the "Barrett's" pattern of CK7/20 was maintained for many cases of BE, the
      sensitivity and specificity were only moderate (65% and 56%, respectively). The
      pattern of staining for the CIM was variable, i.e., some cases showed a CK7/20
      Barrett's pattern despite a normal appearance at endoscopy. The differences
      between this and previous studies may be due to inaccurate visualization of SSBE
      on endoscopy, the development of very early SSBE cases, inter-observer
      variability, fixation differences, or antibody differences. Whatever the cause of
      the differences, if results between laboratories are not comparable, CK7/20
      immunostaining cannot be used to differentiate reliably between IM present in
      biopsy specimens taken from above versus below the Z-line. However, further
      studies should be performed to determine whether the presence or absence of a
      Barrett's pattern of CK7/20 immunostaining could predict progression to dysplasia
      or carcinoma.

PMID- 12065776
TI  - Apoptosis and proliferation in subcutaneous panniculitis-like T-cell lymphoma.
AB  - Subcutaneous panniculitis-like T cell lymphoma (SPTCL), designated recently as a
      distinct clinicopathologic entity in the World Health Organization
      Classification, is a neoplasm composed of cytotoxic T-cells that preferentially
      involves subcutaneous adipose tissue. Histologically, SPTCL is characterized by
      extensive karyorrhectic debris and tumor necrosis suggesting that apoptotic
      mechanisms are involved in its pathogenesis. We assessed the apoptotic index (AI)
      and proliferation rate (PR) of 13 cases of SPTCL by TUNEL test and Ki-67
      immunostaining, respectively. We also immunohistochemically assessed for
      expression of BCL-2 (anti-apoptosis), BAX (pro-apoptosis), and P53 and correlated
      the results with apoptosis and proliferation. We detected a high AI (median 8.1%)
      in 11 cases of SPTCL, and 12 cases had low BCL-2 and high BAX expression. BCL-2
      expression inversely correlated with AI (P <.001) and BAX (P <.001). We found a
      low PR (cutoff > or = 25%) in eight (61%) cases. There was an inverse correlation
      between AI and PR (r = -.58, P =.04). Ten cases were assessed for P53;
      immunostaining results were heterogeneous but P53 expression correlated with
      large cell cytologic features. Our findings demonstrate that SPTCLs have a high
      AI that may be explained by differential expression of BCL-2 and BAX in the
      neoplastic cells.

PMID- 12065775
TI  - Aberrant nuclear localization and gene mutation of beta-catenin in low-grade
      adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may
      be a common denominator for the development of tumors that form morules.
AB  - The salient histopathologic features of low-grade adenocarcinoma of the fetal
      lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) include
      complex glandular structures and morules with biotin-rich optically clear nuclei.
      Interestingly, these characteristic features are shared by the cribriform-morular
      variant of papillary thyroid carcinoma, whose morphology is identical to that of
      familial adenomatous polyposis (FAP)-associated thyroid carcinoma. Furthermore,
      the single reported case of lung cancer associated with FAP was L-FLAC/WDFA.
      These observations lead us to hypothesize that up-regulation of the Wnt signaling
      pathway underlies the development of L-FLAC/WDFA. To verify this hypothesis, 11
      cases of L-FLAC/WDFA, including the one FAP-associated case, eight cases of high
      grade adenocarcinoma of the fetal lung type (H-FLAC), 24 cases of conventional
      pulmonary adenocarcinoma (CAC), and 13 fetal lungs were immunostained for beta
      catenin. All cases of L-FLAC/WDFA showed predominantly aberrant
      nuclear/cytoplasmic expression, especially in budding glands and morules, whereas
      six of eight cases (75%) of H-FLAC and all but one case (96%) of CAC showed
      predominantly membranous expression. Fetal lungs showed nuclear/cytoplasmic
      expression restricted to the distal branching airway epithelium. Mutational
      analysis of exon 3 of the beta-catenin gene in five sporadic cases of L-FLAC/WDFA
      showed a point mutation at codon 34 and codon 37 in two cases, respectively. The
      present study indicates that up-regulating disturbances in the Wnt signaling
      pathway, including mutation of the beta-catenin gene, underlie tumorigenesis of L
      FLAC/WDFA. The expression pattern of beta-catenin in L-FLAC/WDFA resembles that
      of the developing fetal lung airway. With the expression pattern of beta-catenin
      as a marker, most cases of H-FLAC as well as CAC appear to have different
      oncogenic pathways from cases of L-FLAC/WDFA. The present study together with
      other available data also suggests that abnormal up-regulation of the Wnt
      signaling pathway may be a common denominator for the development of tumors with
      morular formation from a variety of anatomic sites.

PMID- 12065777
TI  - Distinct clinical features and outcomes of gastric cancers with microsatellite
      instability.
AB  - Microsatellite instability (MSI) is a hallmark of the DNA mismatch repair
      deficiency that is one of the pathways of gastric carcinogenesis.
      Clinicopathologic characteristics of MSI+ gastric cancers remain unclear. To
      determine the correlation between MSI status and clinical features, we analyzed
      327 consecutive gastric cancers for the occurrence of MSI in the BAT-26 marker.
      Because it has been proven that MSI at BAT-26 reflects the MSI+ phenotype,
      cancers with alteration at BAT-26 were categorized as having the MSI+ phenotype.
      The expressions of hMLH1, hMSH2, p53, MUC1, MUC2, and CEA were evaluated
      immunohistochemically using the tissue array method. The MSI+ phenotype was found
      in 9.5% (31/327) of gastric cancers examined. MSI+ gastric cancers were
      significantly associated with older age, antral location, Borrmann's gross Type
      II, intestinal subtype, lower prevalence of lymph node metastasis, and lower pTNM
      stage (P <.05). By multivariate logistic regression, MSI+ gastric cancers had a
      lower prevalence of lymph node metastasis independent of tumor invasion (P
      <.001). MSI+ gastric cancers displayed frequent frameshift mutations of
      transforming growth factor-beta type II receptor (90.3%), BAX (61.3%), hMSH3
      (38.7%), and E2F4 (61.3%) genes and diminished hMLH1 (24/31) or hMSH2 (4/31)
      expressions. The MSI+ phenotype correlated with patient survival in advanced
      gastric carcinoma (P =.046). In conclusion, MSI+ phenotype in gastric cancers was
      found to have distinct clinicopathologic characteristics and to be predictive of
      a favorable outcome in advanced carcinoma.

PMID- 12065778
TI  - Histological detection of minimal metastatic involvement in axillary sentinel
      nodes: a rational basis for a sensitive methodology usable in daily practice.
AB  - There is no consensus method for the histological analysis of axillary sentinel
      nodes (SN). This study aimed to (1) assess the rate of occult metastases in SN
      using large serial sectioning and immunohistochemistry (IHC), (2) evaluate
      whether occult metastases were predictive of metastases in the downstream
      axillary nodes, and (3) specify a methodology of analysis of SN that could be
      both sensitive and applicable in daily practice. One hundred three patients with
      breast carcinoma underwent SN biopsy and then axillary dissection. SN free of
      tumor at standard examination of one section were sectioned at six levels (150
      microm intervals) and immunostained for cytokeratin. The number and localization
      of labeled metastatic cells (occult metastases) were recorded. In 29 of the 103
      patients (28%), SN were found to be metastatic after standard examination. The SN
      of the remaining 74 patients were further analyzed using IHC. Occult metastases
      were detected in 35 of these patients (47.3%), leading to an overall SN
      involvement rate of 62% (29+35/103). In 33 of these 35 cases, the plurality and
      the dispersion of the immunostained cells implied that the screening of only 3 of
      the 6 levels would have led to the detection of diagnostic positive events. Only
      one of the 35 patients (2.8%) with occult metastases showed metastatic lymph node
      in the downstream axilla. In our series of axillary SN, the analysis of one
      standard histologic section and, when negative, of only three additional sections
      after IHC revealed >60% of metastasis or occult metastasis. Metastasis detected
      by standard analysis had a high predictive value of downstream node metastasis,
      whereas the predictive value of occult metastasis revealed by IHC was poor. The
      clinical significance of occult metastases in SN needs to be specified by long
      term follow-up analysis.

PMID- 12065779
TI  - Posttransplant lymphoproliferative disorders in lung transplant patients: the
      Cleveland Clinic experience.
AB  - PTLD is a well-recognized complication of organ transplantation. Large series of
      heart, renal, and liver transplants have been examined for the incidence and
      behavior of PTLD. However, reports of the incidence and characteristics of PTLDs
      in lung transplant (LTx) patients are few. We report our experience with PTLDs in
      a large series of LTx recipients at a single institution and compare them to
      other solid organ transplant recipient PTLDs seen at our institution. Twenty
      eight patients were found to have PTLD, of whom 8 were lung transplant
      recipients. We evaluated nine PTLD specimens from these 8 patients for their
      histology, immunophenotype (CD20, CD3, EBV-LMP1), EBER status by in situ
      hybridization, and clinical features. The incidence of PTLD was 3.3% (8/244
      patients). The time to development of PTLD, after transplant, was short (median
      time, 7 mo). All were of B-cell lineage. Overall, EBV was demonstrated in 77.7%
      (7 of 9 specimens) of PTLDs. All specimens tested for clonality were found to be
      monoclonal. Five patients died, with a median time to death of only 4.6 months.
      PTLDs in LTx patients are EBV-associated B-cell, predominantly monoclonal
      lymphoid lesions similar to other solid organ transplant PTLDs. Compared with
      other solid organ transplant recipients with PTLD at our institution, PTLDs in
      LTx patients have a propensity to involve the transplanted organ (P =.001,
      Fisher's exact test), occur earlier after transplant (P =.003, Wilcoxon test),
      and have a shorter survival (P =.002, log rank test). Reasons for this may
      include the relatively higher level of immunosuppression required in these
      patients and limited options in decreasing it. Although the incidence is low,
      careful early monitoring of lung transplantation patients is warranted because of
      the poor prognosis of patients developing this complication.

PMID- 12065780
TI  - Determination of HER2 gene amplification by chromogenic in situ hybridization
      (CISH) in archival breast carcinoma.
AB  - PURPOSE: To compare the efficacy of chromogenic in situ hybridization (CISH(TM))
      with fluorescence in situ (FISH) hybridization and immunohistochemistry (IHC) in
      determination of the HER2 status in human breast cancer. MATERIALS AND METHODS:
      HER2 gene amplification was determined on formalin-fixed paraffin-embedded (FFPE)
      sections of 62 invasive breast cancers by FISH and followed by CISH using a
      digoxigenin (DIG)-labeled HER2 DNA probe generated by Subtraction Probe
      Technology (SPT(TM)), and a biotin-labeled chromosome 17 centromeric (chr.17cen)
      probe. The sections were heat treated and enzyme digested. After in situ
      hybridization, the HER2 probe was detected with fluorescein (FITC)-anti-DIG for
      FISH, followed by peroxidase-anti-FITC and diaminobenzidine (DAB) for CISH. The
      chr.17cen probe was detected with peroxidase-streptavidin and DAB. For CISH
      application, HER2 gene copies or chromosome 17 centromeres and morphology of
      cells were easily visualized simultaneously with a 40x objective under bright
      field microscope in hematoxylin-counterstained sections. IHC study of HER2
      overexpression was performed on adjacent sections using a panel of three HER2
      antibodies (TAB 250, CB11, A0485), and staining was scored according to the
      criteria specified in the HercepTest. RESULTS: HER2 gene amplification detected
      by CISH was visualized typically as large DAB-stained clusters or by many dots in
      the nucleus. FISH and CISH identified HER2 gene amplification in 19% of the
      tumors. Chromosome 17 polysomy was detected in 31% of the tumors. HER2
      overexpression was demonstrated in 19% (TAB 250), 23% (CB11), and 36% (A0485) of
      the tumors. Complete concordance between the results of CISH with FISH, TAB 250,
      CB11, and A0485 was seen in 100%, 97%, 94%, and 84% of the cases, respectively.
      CONCLUSION: By permitting observation of morphology using a bright-field
      microscope, CISH is an accurate, practical, and economical approach to screen
      HER2 status in breast cancers. It is a useful methodology for confirming
      ambiguous IHC results.

PMID- 12065781
TI  - Erdheim-Chester disease: case report, PCR-based analysis of clonality, and review
      of literature.
AB  - Erdheim-Chester disease (ECD) is a rare, distinct clinicopathologic entity with
      nearly pathognomonic radiographic features. The lesions consist of lipid-storing
      CD68 (+), CD1a (-) non-Langerhans' cell histiocytes, either localized to the bone
      or involving multiple organ systems in the body. Whether these histiocytic
      proliferations represent monoclonal neoplastic populations or are part of a
      polyclonal reactive process is unclear. We present a case report of ECD in a 35
      year-old African-American woman with a progressive course over 6 years. We
      investigated the clonality of the histiocytes using the HUMARA assay on paraffin
      embedded tissue sections but did not find any evidence that these cells represent
      a monoclonal population. In this report, the characteristics of ECD are reviewed,
      the genetic basis of the HUMARA assay is discussed, and our results in the
      context of other clonality investigations reported in the literature to date are
      summarized.

PMID- 12065782
TI  - Primary peripheral PNET/Ewing's sarcoma of the dura: a clinicopathologic entity
      distinct from central PNET.
AB  - We describe two cases of peripheral primitive neuroectodermal tumor-Ewing's
      sarcoma (PNET-ES) arising intracranially in the leptomeninges. Both tumors
      exhibited a primitive undifferentiated round-cell morphology. Immunohistochemical
      stains revealed strong membrane expression of CD99 in both cases. A
      t(11;22)(q24;q12) could be demonstrated with reverse transcriptase-polymerase
      chain reaction in one case, whereas fluorescence in situ hybridization analysis
      performed in the second case showed a rearrangement of the EWS gene. The
      occurrence of PNET-ES at this site is very unusual. Immunophenotypical as well as
      genetic analysis play a key role in the diagnosis and the distinction from
      central PNET.

PMID- 12065784
TI  - NCI remains committed to current mammography guidelines.

PMID- 12065783
TI  - A novel type of SYT/SSX fusion: methodological and biological implications.
AB  - Synovial sarcoma (SS) is a rare soft-tissue tumor that affects children and young
      adults. It is characterized by the chromosomal translocation
      t(X;18)(p11.2;q11.2), which results in the fusion of the SYT gene on chromosome
      18 with a SSX gene on chromosome X. In the majority of cases, SYT is fused to
      exon 5 of SSX1 (64%), SSX2 (36%), or, rarely, SSX4. A novel fusion transcript
      variant deriving from the fusion of SYT to exon 6 of SSX4 gene (SYT/SSX4v) was
      found coexpressed in one of the previously reported SYT/SSX4 cases. In the
      present investigation, we describe a new SS case that was previously shown to be
      negative for SYT/SSX1 and SYT/SSX2 expression by conventional reverse
      transcription polymerase chain reaction (RT-PCR) methods. By redesigning and
      optimizing the RT-PCR protocol, we were able to detect SYT/SSX4v as the sole
      fusion transcript expressed in this tumor sample. This finding suggests that this
      novel fusion gene, which involves exon 6 of SSX only, is sufficient to keep the
      transforming function conferred by the SYT/SSX translocation of SS. In about 3%
      of morphologically, ultrastructurally, and immunohistochemically defined SS, the
      SYT/SSX fusion transcript is not detected using conventional RT-PCR. Here we
      demonstrate that optimization of the RT-PCR method is important for detecting
      different and unexpected SYT/SSX variants, which otherwise could be overlooked.
      Using nine cases of SS in which SYT/SSX fusion transcripts were not detected by
      conventional RT-PCR methods, we demonstrate the presence of SYT/SSX transcripts
      in two cases using the proposed RT-PCR approach. Applications of optimized RT-PCR
      can contribute to reduce false-negative SYT/SSX SS cases reported in literature.

PMID- 12065785
TI  - Seeking calmer waters in a sea of controversy.

PMID- 12065786
TI  - The mammography controversy.

PMID- 12065787
TI  - Choosing chemotherapy for lung cancer based on cost: not yet.

PMID- 12065788
TI  - Does economics matter when treating advanced non-small cell lung cancer?

PMID- 12065789
TI  - Interpreting measures of treatment effect in cancer clinical trials.
AB  - The efficacy of a new cancer regimen is usually assessed by analyzing outcomes
      such as tumor response and overall survival. Many publications summarizing
      results of cancer clinical trials report measures such as odds ratios and hazard
      ratios, as these are the estimators of treatment effect obtained from regression
      models used to analyze the data. However, these measures are sometimes
      misinterpreted, as they are not necessarily familiar to many readers. The most
      common mistake is to interpret both measures as relative risks, an interpretation
      that can lead to an incorrect impression of the impact of the treatment on
      response and survival.

PMID- 12065790
TI  - Carcinoma of the anus: strategies in management.
AB  - The management of anal cancer underwent an interesting transformation over the
      last two decades. Prior to this period, the standard definitive treatment for
      carcinoma of the anal canal was abdominal-perineal resection, which necessitated
      a permanent colostomy. The organ preservation concept appeared following the
      discovery of a high complete response rate from preoperative combined
      chemoradiation prior to abdominal-perineal resection. The organ preservation
      method of treatment rapidly gained popularity and ultimately saved a large number
      of patients from undergoing abdominal-perineal resection and colostomy.
      Chemoradiation treatment itself subsequently went through an evolutionary
      process. Several studies have sought to define the optimal chemotherapeutic
      regimen as well as radiation treatment dose and fractionation. Ongoing studies
      attempt to define an optimal treatment regimen that yields a higher cure rate
      while minimizing toxicity. We review the etiology, epidemiology, and treatment
      regimens for anal cancer.

PMID- 12065791
TI  - Assessing a decade of progress in cancer control.
AB  - The age-adjusted death rate from cancer peaked in the U.S. in 1990, and has
      declined steadily since then. We assess reasons for this progress by examining
      trends in cancer mortality by age, gender, and cause, using underlying cause
      mortality data from the Centers for Disease Control. Mortality rates for 2000
      were estimated using models based on 1979 through 1997 mortality data. Indirect
      standardization was used to calculate the expected number of cancer deaths in
      2000, by age, gender, and cause, assuming that the rates in 1990 had not changed.
      In the U.S. in 2000, there were an estimated 500,000 deaths from cancer; 64,000
      (12.7%) fewer than expected, with 51,900 fewer cancer deaths among men and 12,200
      fewer deaths among women. The decline in deaths among men resulted from fewer
      deaths from lung cancer (20,800), colon cancer (6,700), and prostate cancer
      (12,900). The decline in deaths among women resulted from fewer deaths from
      breast cancer (11,100) and colon cancer (4,200), but there were more deaths from
      lung cancer (6,500). Among women over the age of 75, 5,000 more died of cancer
      than expected. Declines in lung, prostate, and colon cancer deaths among men and
      breast and colon cancer among women account for 86% of the recent decline in
      cancer deaths over the past decade.

PMID- 12065793
TI  - Unique features of the mode of action of ET-743.
AB  - This paper describes the current knowledge of the primary mode of action of a
      natural product, ecteinascidin 743 (ET-743), derived from the marine tunicate
      Ecteinascidia turbinata. ET-743 was initially selected for preclinical
      development because of its potent antitumor activity observed against several
      human solid tumor types. In vitro, the drug is cytotoxic in the nanomolar range,
      and in the case of some very sensitive cell lines, in the picomolar range. The
      large potency differences observed among several solid tumor types indicate that
      this compound possesses some tumor selectivity, but the molecular basis of these
      differential effects remains to be elucidated. The present studies were
      undertaken to evaluate the mechanism of action of ET-743 in this context. The
      available information on ET-743 binding to DNA and its effects on transcriptional
      regulation point to a unique behavior of this drug, as it independently affects
      specific gene transcription in a promoter-dependent way. In addition, ET-743
      shows a peculiar pattern of selectivity in cells with different defects in their
      DNA-repair pathways. These results highlight a unique property of ET-743,
      possibly explaining why it possesses antitumor activity against tumors that are
      refractory to standard anticancer drugs, all of which certainly act by mechanisms
      that are different from that of ET-743.

PMID- 12065792
TI  - A phase II study of intravenous navelbine and doxorubicin combination in
      previously untreated advanced breast carcinoma.
AB  - PURPOSE: The combination of vinorelbine and doxorubicin, two very active drugs in
      metastatic breast cancer, has demonstrated impressive results in terms of
      efficacy, at the price of cardiac toxicity (10% grades 2-4) due to the cumulative
      dose of doxorubicin delivered. This study was designed to divide the dose of
      doxorubicin into two administrations (day 1 and 8) in order to reduce the
      toxicity profile, while keeping the same level of efficacy. PATIENTS AND METHODS:
      Thirty-eight chemotherapy-naive metastatic breast cancer patients entered into
      the study and were treated with vinorelbine, 25 mg/m(2), and doxorubicin, 25
      mg/m(2), both on days 1 and 8, every 3 weeks. Thirty-seven patients were
      evaluable for efficacy and 38 for tolerance; 71% of the patients presented with
      visceral metastases. RESULTS: Patients received a median of seven cycles and
      94.9% of the intended dose intensity of both drugs. Grade 3-4 neutropenia was
      reported in 10% of cycles. Alopecia was reported in 89.5% of the patients, and
      grade 2 nausea/vomiting in 9.3% of the cycles. Grade 1-2 cardiac toxicity was
      noted in 23.7% of the patients. The objective response rate of the patients was
      78.4% (nearly 81% for patients with visceral metastases); the median duration of
      response was 11.6 months, the median survival 21.6 months, and the 1-year
      survival 75.2%. CONCLUSION: This schedule of vinorelbine/doxorubicin represents
      an active and well-tolerated combination.

PMID- 12065794
TI  - Progress and promise in the treatment of indolent lymphomas.
AB  - In the era of conventional alkylating agent-based chemotherapy, advanced stage
      indolent lymphoma has been considered incurable. The failure of our traditional
      therapies to cure these patients, coupled with the indolent course of the disease
      and the elderly population affected, has fostered a nihilistic attitude about the
      treatment of these diseases. Twenty years ago, in the absence of interesting
      alternatives to alkylating agents, judicious use and reuse of alkylators was
      perhaps the best we could do. There are now many reasons for optimism and
      excitement in the treatment of these diseases, including the availability of
      promising agents such as interferon-alpha, the nucleoside analogues, and
      rituximab. Radioimmunotherapy will also likely play a role in future therapy
      programs. Allogeneic stem cell transplantation is a high-risk approach that is
      not an option for all patients, but it has the potential to cure patients, even
      in the setting of relapse. Mini-allogeneic transplantation may permit an approach
      to allogeneic transplantation that is better tolerated than standard transplant
      strategies. In addition to these therapy options, biological insights have
      provided new options for monitoring patients. Molecular monitoring (polymerase
      chain reaction for bcl-2) is a stringent measure of short-term treatment
      efficacy, and one that correlates with durability of remission, i.e., it is a
      surrogate marker by which to judge treatment efficacy. There used to be a limited
      number of conventional treatment approaches, which consistently failed. The
      pendulum has swung. There are now many promising new options. It is time to plan
      and conduct trials that are geared for success.

PMID- 12065795
TI  - Is there a preferred combination chemotherapy regimen for metastastic non-small
      cell lung cancer?
AB  - Since over 70% of patients with non-small cell lung cancer (NSCLC) have advanced
      (locally advanced or metastatic) disease, the majority of NSCLC patients might
      benefit from chemotherapy. During the past decade, a number of new agents
      (paclitaxel, docetaxel, gemcitabine, vinorelbine, irinotecan, and topotecan) have
      been found to be effective against lung cancer. These agents have been combined
      with cisplatin, carboplatin, and nonplatinum drugs to treat NSCLC. They, in
      general, produce median survival times of 8-10 months and 1- and 2-year survival
      rates of 35%-40% and 10%-15%, respectively. Based on this review, there is not a
      preferred combination chemotherapy regimen to treat advanced NSCLC patients.
      However, there are a number of different regimens from which to choose.

PMID- 12065796
TI  - Small cell lung cancer: current therapy and promising new regimens.
AB  - In this review, we cover current therapy and promising new regimens and highlight
      areas where improvement is needed in the management of small cell lung cancer.

PMID- 12065797
TI  - Preoperative therapy in breast cancer: lessons from the treatment of locally
      advanced disease.
AB  - The greater use of screening has changed the stage distribution of breast cancer,
      and an increasing number of patients are diagnosed with earlier stages of the
      disease. Still, locally advanced breast cancer (LABC) remains a major clinical
      problem in the United States and a common presentation in many parts of the
      world. There is no standard definition of LABC. One commonly used includes
      patients with large primary tumors greater than 5 cm (T3) or with skin/chest wall
      involvement (T4), and/or fixed axillary (N2) or ipsilateral internal mammary (N3)
      lymph node involvement. According to the tumor node metastasis staging, these
      usually include stage IIIa (T0-2N2 or T3N1-2) and stage IIIb (T4Nx or TxN3)
      disease. Inflammatory breast cancer (T4d) is included in most classifications
      despite its distinct clinical behavior and worse prognosis overall, but it serves
      as an example of combined modality intervention. Historically, the term LABC has
      been applied to those clinical presentations where the disease is considered
      inoperable. However, these therapeutic principles (including preoperative or
      primary systemic therapy [PST]) are increasingly being applied to patients
      presenting with tumors greater than 5 cm and negative lymph nodes (stage IIb
      T3N0) or even smaller tumors, who are considered to have operable disease and a
      better outcome than those traditionally classified as having LABC. PST is
      increasingly being used in otherwise operable stage I and II patients aiming at
      greater rates of breast conservation and earlier efficacy assessment. This
      article reviews many of these issues and ongoing research questions.

PMID- 12065798
TI  - Adjuvant therapy for breast cancer: recommendations for management based on
      consensus review and recent clinical trials.
AB  - Determining the optimal individual adjuvant systemic therapy for breast cancer
      patients is a challenging undertaking because it requires translating data from
      clinical trials that have involved thousands of patients into a highly
      individualized, risk-adjusted approach for the patient at hand. Choosing adjuvant
      therapy for women with breast cancer includes consideration of four issues: A)
      evaluation of risk of relapse; B) extrapolation of results from clinical trials;
      C) therapeutic ratio, and D) the patient's preferences following a thorough
      discussion with her physician. Data from recently completed phase III adjuvant
      trials and worldwide consensus conferences document the benefits of adjuvant
      therapy in improving disease-free survival and overall survival for patients
      diagnosed with invasive breast cancer >1.0 cm in size. The benefits of hormonal
      therapy are clear, but limited to patients with estrogen receptor-positive breast
      cancer. Anthracyclines lead to improved outcomes compared with nonanthracycline
      regimens. Taxanes appear to improve disease-free survival in patients with node
      positive disease, although longer follow-up is required to assess their impact on
      overall survival. Some countries have reported a reduction in the mortality rate
      from breast cancer over the past several years. The improved survival rate is
      due, at least in part, to the use of adjuvant systemic therapy. Ongoing studies
      are evaluating targeted therapies, with the potential of remarkably improving
      patient outcome.

PMID- 12065800
TI  - The molecular perspective: Bcl-2 and apoptosis.

PMID- 12065799
TI  - When does the responsibility of our care end: bereavement.
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The
      Schwartz Center is a non-profit organization dedicated to supporting and
      advancing compassionate health care delivery, which provides hope to the patient,
      support to caregivers, and sustenance to the healing process. The center sponsors
      the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers
      reflect on important psychosocial issues faced by patients, their families, and
      their caregivers, and gain insight and support from fellow staff members. Two
      vignettes are presented of a caregiver's response to the death of a patient,
      contrasting the extremes of involved compassion for the family and fractured
      relationships. Grief for loss is an inevitable part of life and a common part of
      cancer care. Support of the bereaved may be one of the hardest tasks for cancer
      care professionals, who are confronted with the limits of modern medicine. There
      is a responsibility to provide grieving families with support and care; care that
      goes beyond the death. A compassionate response helps both those who suffer and
      those who care. Complicated and uncomplicated bereavement, grief reactions,
      resources for bereavement counseling, and the role of condolence letters are
      reviewed.

PMID- 12065803
TI  - Global allocation rules for patterns of biomass partitioning.

PMID- 12065804
TI  - A cultural change in UK universities.

PMID- 12065805
TI  - National security. Research chiefs hunt for details in proposal for new
      department.

PMID- 12065806
TI  - Air pollution risks. Software glitch threw off mortality estimates.

PMID- 12065807
TI  - DOE weapons labs. Livermore keeps it all in the family.

PMID- 12065808
TI  - Spintronics. Magnetic gate opens new computing path.

PMID- 12065809
TI  - Genetically modified food. TV drama sparks scientific backlash.

PMID- 12065811
TI  - Archaeology. Millions pledged for Afghan restoration.

PMID- 12065810
TI  - Ecology. A coral by any other name.

PMID- 12065813
TI  - Astronomy. Lucky catch identifies disintegrating cluster.

PMID- 12065812
TI  - Exoplanets. 'New Jupiter' turns up in strange company.

PMID- 12065814
TI  - Clinical trials. Agency wants to stop shopping for best deal.

PMID- 12065815
TI  - Fort Detrick. On biowarfare's frontline.

PMID- 12065816
TI  - Claire Fraser profile. TIGR's chief: results without the roar.

PMID- 12065817
TI  - Brazilian ecosystems: History, management, and preservation. South American
      landscapes: ancient and modern.

PMID- 12065818
TI  - Astronomy. Hubble gets new IR eyes.

PMID- 12065819
TI  - American Geophysical Union meeting. Of Mars water, old cold, and deep talk.

PMID- 12065820
TI  - Climate change. Dangerous climate impacts and the Kyoto Protocol.

PMID- 12065821
TI  - Materials science. Orienting ferroelectric films.

PMID- 12065822
TI  - Neuroscience. Can we teach the cerebellum new tricks?

PMID- 12065823
TI  - Oceanography. Small critters--big effects.

PMID- 12065824
TI  - Origin of life. Some like it hot, but not the first biomolecules.

PMID- 12065825
TI  - Evolution: retrospective. Stephen Jay Gould (1941-2002).

PMID- 12065826
TI  - Flow and storage in groundwater systems.
AB  - The dynamic nature of groundwater is not readily apparent, except where discharge
      is focused at springs or where recharge enters sinkholes. Yet groundwater flow
      and storage are continually changing in response to human and climatic stresses.
      Wise development of groundwater resources requires a more complete understanding
      of these changes in flow and storage and of their effects on the terrestrial
      environment and on numerous surface-water features and their biota.

PMID- 12065828
TI  - Polymer nanotubes by wetting of ordered porous templates.

PMID- 12065827
TI  - Toxic proteins in neurodegenerative disease.
AB  - A broad range of neurodegenerative disorders is characterized by neuronal damage
      that may be caused by toxic, aggregation-prone proteins. As genes are identified
      for these disorders and cell culture and animal models are developed, it has
      become clear that a major effect of mutations in these genes is the abnormal
      processing and accumulation of misfolded protein in neuronal inclusions and
      plaques. Increased understanding of the cellular mechanisms for disposal of
      abnormal proteins and of the effects of toxic protein accumulation on neuronal
      survival may allow the development of rational, effective treatment for these
      disorders.

PMID- 12065829
TI  - Temporal specificity in the cortical plasticity of visual space representation.
AB  - The circuitry and function of mammalian visual cortex are shaped by patterns of
      visual stimuli, a plasticity likely mediated by synaptic modifications. In the
      adult cat, asynchronous visual stimuli in two adjacent retinal regions controlled
      the relative spike timing of two groups of cortical neurons with high precision.
      This asynchronous pairing induced rapid modifications of intracortical
      connections and shifts in receptive fields. These changes depended on the
      temporal order and interval between visual stimuli in a manner consistent with
      spike timing-dependent synaptic plasticity. Parallel to the cortical
      modifications found in the cat, such asynchronous visual stimuli also induced
      shifts in human spatial perception.

PMID- 12065830
TI  - Submicrometer ferromagnetic NOT gate and shift register.
AB  - An all-metallic submicrometer device is demonstrated experimentally at room
      temperature that performs logical NOT operations on magnetic logic signals. When
      this two-terminal ferromagnetic structure is incorporated into a magnetic
      feedback loop, the junction performs a frequency division operation on an applied
      oscillating magnetic field. Up to 11 of these junctions are then directly linked
      together to create a magnetic shift register.

PMID- 12065832
TI  - A reversible solid-state crystalline transformation in a metal phosphide induced
      by redox chemistry.
AB  - We demonstrate low-potential intercalation of lithium in a solid-state metal
      phosphide. A topotactic first-order transition between different but related
      crystal structures at room temperature takes place by an electrochemical redox
      process: MnP4 <--> Li7MnP4. The P-P bonds in the MnP4 structure are cleaved at
      the time of Li insertion (reduction) to produce crystalline Li7MnP4 and are
      reformed after reoxidation to MnP4, thereby acting as an electron storage
      reservoir. This is an unusual example of facile covalent bond breaking within the
      crystalline solid state that can be reversed by the input of electrochemical
      energy.

PMID- 12065831
TI  - Ferroelectric Bi3.25La0.75Ti3O12 films of uniform a-axis orientation on silicon
      substrates.
AB  - The use of bismuth-layered perovskite films for planar-type nonvolatile
      ferroelectric random-access memories requires films with spontaneous polarization
      normal to the plane of growth. Epitaxially twinned a axis-oriented La-substituted
      Bi4Ti3O12 (BLT) thin films whose spontaneous polarization is entirely along the
      film normal were grown by pulsed laser deposition on yttria-stabilized zirconia
      buffered Si(100) substrates using SrRuO3 as bottom electrodes. Even though the
      (118) orientation competes with the (100) orientation, epitaxial films with
      almost pure (100) orientation were grown using very thin, strained SrRuO3
      electrode layers and kinetic growth conditions, including high growth rates and
      high oxygen background pressures to facilitate oxygen incorporation into the
      growing film. Films with the a-axis orientation and having their polarization
      entirely along the direction normal to the film plane can achieve a remanent
      polarization of 32 microcoulombs per square centimeter.

PMID- 12065833
TI  - Co-seismic strike-slip and rupture length produced by the 2001 Ms 8.1 Central
      Kunlun earthquake.
AB  - Field investigations show that the surface wave magnitude (Ms) 8.1 Central Kunlun
      earthquake (Tibetan plateau) of 14 November 2001 produced a nearly 400-kilometer
      long surface rupture zone, with as much as 16.3 meters of left-lateral strike
      slip along the active Kunlun fault in northern Tibet. The rupture length and
      maximum displacement are the largest among the co-seismic surface rupture zones
      reported on so far. The strike-slip motion and the large rupture length generated
      by the earthquake indicate that the Kunlun fault partitions its deformation into
      an eastward extrusion of Tibet to accommodate the continuing penetration of the
      Indian plate into the Eurasian plate.

PMID- 12065834
TI  - A 160,000-year record of dune development and atmospheric circulation in Southern
      Arabia.
AB  - Aeolian deposits in the Wahiba Sands, Sultanate of Oman, reveal patterns of
      atmospheric circulation over the past 160,000 years. Luminescence dating
      indicates a correlation of dune activity with periods of low global sea level and
      decreased monsoon intensity. Evidence from dune orientation and sedimentary
      structures shows exclusively northbound transport of sand during times of high-
      latitude glaciation. These results are in contrast to the current
      paleocirculation model that assumes an increase of northwesterly winds because of
      a southward shift of the Intertropical Convergence Zone. Our results indicate
      that the circulation pattern during glacial times was comparable to that of the
      present.

PMID- 12065835
TI  - Rapid bottom melting widespread near Antarctic Ice Sheet grounding lines.
AB  - As continental ice from Antarctica reaches the grounding line and begins to
      float, its underside melts into the ocean. Results obtained with satellite radar
      interferometry reveal that bottom melt rates experienced by large outlet glaciers
      near their grounding lines are far higher than generally assumed. The melting
      rate is positively correlated with thermal forcing, increasing by 1 meter per
      year for each 0.1 degrees C rise in ocean temperature. Where deep water has
      direct access to grounding lines, glaciers and ice shelves are vulnerable to
      ongoing increases in ocean temperature.

PMID- 12065836
TI  - Hybridization and the evolution of reef coral diversity.
AB  - Hundreds of coral species coexist sympatrically on reefs, reproducing in mass
      spawning events where hybridization appears common. In the Caribbean, DNA
      sequence data from all three sympatric Acropora corals show that mass spawning
      does not erode species barriers. Species A. cervicornis and A. palmata are
      distinct at two nuclear loci or share ancestral alleles. Morphotypes historically
      given the name Acropora prolifera are entirely F(1) hybrids of these two species,
      showing morphologies that depend on which species provides the egg for
      hybridization. Although selection limits the evolutionary potential of hybrids,
      F(1) individuals can reproduce asexually and form long-lived, potentially
      immortal hybrids with unique morphologies.

PMID- 12065837
TI  - RopGAP4-dependent Rop GTPase rheostat control of Arabidopsis oxygen deprivation
      tolerance.
AB  - Transient soil flooding limits cellular oxygen to roots and reduces crop yield.
      Plant response to oxygen deprivation involves increased expression of the alcohol
      dehydrogenase gene (ADH) and ethanolic fermentation. Disruption of the
      Arabidopsis gene that encodes Rop (RHO-like small G protein of plants) guanosine
      triphosphatase (GTPase) activating protein 4 (ROPGAP4), a Rop deactivator,
      elevates ADH expression in response to oxygen deprivation but decreases tolerance
      to stress. Rop-dependent production of hydrogen peroxide via a diphenylene
      iodonium chloride-sensitive calcium-dependent reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase is necessary for induction of both ADH and
      RopGAP4 expression. Tolerance to oxygen deprivation requires Rop activation and
      RopGAP4-dependent negative feedback regulation. This Rop signal transduction
      rheostat balances the ability to increase ethanolic fermentation with survival.

PMID- 12065838
TI  - AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts.
AB  - Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is
      indispensable for somatic hypermutation (SHM), class switch recombination, and
      gene conversion of immunoglobulin genes, which indicates a common molecular
      mechanism for these phenomena. Here we show that ectopic expression of AID alone
      can induce hypermutation in an artificial GFP substrate in NIH 3T3 murine
      fibroblast cells. The frequency of mutations was closely correlated with the
      level of transcription of the target gene, and the distribution of mutations in
      NIH 3T3 cells was similar to those of SHM in B lymphocytes. These results
      indicate that AID is sufficient for the generation of SHM in an actively
      transcribed gene in fibroblasts, as well as B cells, and that any of the required
      cofactors must be present in these fibroblasts.

PMID- 12065839
TI  - Induction of T helper type 2 immunity by a point mutation in the LAT adaptor.
AB  - The transmembrane protein LAT (linker for activation of T cells) couples the T
      cell receptor (TCR) to downstream signaling effectors. Mice homozygous for a
      mutation of a single LAT tyrosine residue showed impeded T cell development.
      However, later they accumulated polyclonal helper T (TH) cells that chronically
      produced type 2 cytokines in large amounts. This exaggerated TH2 differentiation
      caused tissue eosinophilia and massive maturation of plasma cells secreting to
      immunoglobulins of the E and G1 isotypes. This paradoxical phenotype establishes
      an unanticipated inhibitory function for LAT that is critical for the
      differentiation and homeostasis of TH cells.

PMID- 12065841
TI  - Cerebellum activation associated with performance change but not motor learning.
AB  - The issue of whether the cerebellum contributes to motor skill learning is
      controversial, principally because of the difficulty of separating the effects of
      motor learning from changes in performance. We performed a functional magnetic
      resonance imaging investigation during an implicit, motor sequence-learning task
      that was designed to separate these two processes. During the sequence-encoding
      phase, human participants performed a concurrent distractor task that served to
      suppress the performance changes associated with learning. Upon removal of the
      distractor, participants showed evidence of having learned. No cerebellar
      activation was associated with the learning phase, despite extensive involvement
      of other cortical and subcortical regions. There was, however, significant
      cerebellar activation during the expression of learning; thus, the cerebellum
      does not contribute to learning of the motor skill itself but is engaged
      primarily in the modification of performance.

PMID- 12065840
TI  - A LAT mutation that inhibits T cell development yet induces lymphoproliferation.
AB  - Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T
      cells) exhibited an early block in T cell maturation but later developed a
      polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell
      antigen receptor (TCR)-induced activation of phospholipase C-gamma1 (PLC-gamma1)
      and of nuclear factor of activated T cells, calcium influx, interleukin-2
      production, and cell death were reduced or abrogated in T cells from LAT mutant
      mice. In contrast, TCR-induced Erk activation was intact. These results identify
      a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T
      cell development and homeostasis.

PMID- 12065842
TI  - Correlated bursts of activity in the neonatal hippocampus in vivo.
AB  - The behavior of immature cortical networks in vivo remains largely unknown. Using
      multisite extracellular and patch-clamp recordings, we observed recurrent bursts
      of synchronized neuronal activity lasting 0.5 to 3 seconds that occurred
      spontaneously in the hippocampus of freely moving and anesthetized rat pups. The
      influence of slow rhythms (0.33 and 0.1 hertz) and the contribution of both gamma
      aminobutyric acid A-mediated and glutamate receptor-mediated synaptic signals in
      the generation of hippocampal bursts was reminiscent of giant depolarizing
      potentials observed in vitro. This earliest pattern, which diversifies during the
      second postnatal week, could provide correlated activity for immature neurons and
      may underlie activity-dependent maturation of the hippocampal network.

PMID- 12065843
TI  - A new antibody recognizing the vIII mutation of human epidermal growth factor
      receptor.
AB  - The epidermal growth factor receptor (EGFR) gene is frequently amplified and the
      receptor overexpressed in different types of human tumors. Furthermore, genomic
      rearrangements can cause expression of modified receptors, as one frequently
      occurring truncated form, EGFRvIII. This mutated receptor has previously been
      described and is formed by a 267-amino acid in-frame deletion and an insertion of
      a glycine in the fusion junction of the extracellular domain. EGFRvIII is a tumor
      specific marker and therefore of interest for diagnostic and therapeutic
      applications. In this study we report on a new monoclonal antibody (Ua30:2)
      directed to the mutation site of EGFRvIII. The antibody was generated by
      immunization of mice with a synthetic peptide corresponding to the mutated
      sequence of the receptor. The affinity of Ua30:2 was found to be high [K(d) = 45
      nM (Biacore) and 80 nM (saturation analysis)]. Immunohistochemistry in tissue
      sections from human gliomas demonstrated a similar expression pattern for Ua30:2
      as for the recently characterized antibodies L8A4 and DH8.3. The antibody binding
      was EGFRvIII specific with no measurable cross-reactivity to the wild-type
      receptor, wtEGFR, as analyzed both with displacement analysis, Western blots and
      immunohistochemistry. The new antibody is a candidate for radioimmunotargeting
      aiming at diagnostic and therapeutic applications.

PMID- 12065844
TI  - Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer
      predicting the response to second-line hormone or chemotherapy.
AB  - Concentrations of soluble c-erbB-2 were determined in the sera of 64 patients
      with distant metastasis from advanced breast cancer receiving second-line hormone
      or chemotherapy in comparison to 35 breast cancer patients without detectable
      recurrent disease and 17 healthy blood donors. The sera of non-metastatic breast
      cancer patients contained s-erbB-2 concentrations similar to those of healthy
      blood donors. Patients with distant metastasis from advanced breast cancer had
      significantly higher values of s-erbB-2 in comparison to patients with non
      disseminated disease (mean: 59.6 vs. 11.6 U/ml; p = 0.022). A significant
      correlation was observed between s-erbB-2 serum levels and serum LDH
      concentrations (p < 0.001), levels of alkaline phosphatase (p < 0.001), and the
      presence of hepatic metastasis (p = 0.001). Time to tumor progression was
      significantly shorter in patients with s-erbB-2 levels above 40 U/ml (mean: 23.4
      vs. 56.7 months; p = 0.002). Furthermore, breast cancer patients with hepatic
      metastasis and those with elevated s-erbB-2 serum levels above 40 U/ml had
      limited response to hormone or chemotherapy. Non-responders had significantly
      higher s-erbB-2 levels (mean: 270.3, range: 42-500 U/ml;) compared with the
      responder group (mean: 23.1, range: 0-149 U/ml; p < 0.001). Logistic regression
      analysis indicated that elevated s-erbB-2 serum levels above 40 U/ml
      independently predicted an unfavorable response to second-line hormone or
      chemotherapy in patients with advanced metastatic breast cancer.

PMID- 12065845
TI  - E2F-1 gene therapy induces apoptosis and increases chemosensitivity in human
      pancreatic carcinoma cells.
AB  - Pancreatic cancer is often resistant to conventional chemotherapy. In this study,
      we examined the role of adenovirus-mediated overexpression of E2F-1 in inducing
      apoptosis and increasing the sensitivity of pancreatic cancer cells to
      chemotherapeutic agents. MIA PaCa-2 pancreatic head exocrine adenocarcinoma cells
      (mutant p53) were treated by mock infection or adenoviruses expressing beta
      galactosidase or E2F-1 (Ad-E2F-1) alone or in combination with sublethal
      concentrations of each chemotherapeutic drug. Cell growth and viability were
      assessed at selected time points. Apoptosis was evaluated by flow cytometry,
      characteristic changes in cell morphology and poly (ADP-ribose) polymerase (PARP)
      cleavage. Western blot analysis was used to examine the expression of E2F-1 and
      Bcl-2 family member proteins and PARP cleavage. Western blot analysis revealed
      marked overexpression of E2F-1 at a multiplicity of infection (MOI) of 20 and 70.
      By 3 days after infection, Ad-E2F-1 treatment at an MOI of 70 resulted in
      approximately a 20-fold reduction in cell growth and 60% reduction in cell
      viability as compared to mock-infected cells. Cell cycle analysis, PARP cleavage
      and changes in cell morphology supported apoptosis as the mechanism of cell death
      in response to E2F-1. In order to test the efficacy of treatment with a
      combination of gene therapy and chemotherapy, we utilized concentrations of Ad
      E2F-1 which reduced viability to 50% in combination with each chemotherapeutic
      agent. Cotreatment of the cells with E2F-1 virus and roscovitine (ROS) or
      etoposide resulted in an additive effect on cell growth inhibition and induction
      of apoptosis. Interestingly, 5-fluorouracil did not cooperate with Ad-E2F-1 in
      the mediation of tumor death or inhibition of cell growth. Immunoblotting for Bcl
      2 family members revealed no significant changes in the expression levels of Bcl
      2, Bcl X(L), Bax or Bak following gene or 'chemogene' therapy with E2F-1.
      However, a Bax cleavage product was noted which was substantially increased by
      cotreatment with ROS or etoposide. E2F-1 overexpression initiates apoptosis and
      suppresses growth in pancreatic MIA PaCa-2 cells in vitro. E2F-1-mediated
      apoptosis was not associated with significant changes in the expression of Bcl-2
      family member proteins in these pancreatic cancer cells. ROS and etoposide, when
      combined with E2F-1 overexpression, induce apoptosis in an additive manner. This
      chemogene combination may provide a potentially useful therapeutic strategy for
      advanced pancreatic cancer.

PMID- 12065846
TI  - Telomerase assay and HPV 16/18 typing as adjunct to conventional cytological
      cervical cancer screening.
AB  - OBJECTIVE: This study aims at exploring the potential use of telomerase activity
      assay and typing of human papillomaviruses (HPV) 16 and 18 in improving the
      identification of high-grade cervical intraepithelial neoplasia (CIN). METHODS:
      From 86 women with normal cervical smears and from 114 patients with abnormal
      cervical smears cervical scrapings were collected. The telomerase activity was
      assayed using the Telomerase Repeat Amplification Protocol, and HPV was detected
      using consensus primers and specific primers for HPV 16 and HPV 18. RESULTS: HPV
      16 in cervical scrapes was significantly associated with high-grade squamous
      epithelial lesions on cytology and with high-grade CIN, i.e., CIN 2/3 on biopsy.
      The detection of HPV 18 or telomerase activity had no significant association
      with high-grade squamous intraepithelial lesions or high-grade CIN. CONCLUSION:
      The use of the telomerase activity assay in cervical scrapes, unlike HPV 16
      typing, did not improve the detection of high-grade CIN.

PMID- 12065847
TI  - Egr1 transcription factor: multiple roles in prostate tumor cell growth and
      survival.
AB  - The transcription factor, Egr1, so-called because it is encoded by the immediate
      early growth response gene, Egr1, is rapidly induced by growth factors to
      transduce the proliferative signal. The induction of Egr1 by external stimuli is
      generally transient but appears to be sustained in some prostate tumor cell lines
      and tumors, suggesting that Egr1 stimulates tumor cell growth. In contradiction,
      in breast, lung and brain tumors, Egr1 expression is often absent or reduced and
      when re-expressed, results in growth suppression. Re-expression of Egr1 in tumor
      cells also leads to antiapoptotic activity, which would encourage tumor cell
      survival. Egr1 is also required for, or stimulates, the differentiation of
      several cell types. Another contradiction is that after stress stimuli to some
      cell types, Egr1 is required for programmed cell death or apoptosis in both
      normal and tumor cells. Egr1 also plays a role in tumor progression, through the
      hypoxic signal generated in growing tumors. Egr1 is highly induced under these
      conditions and its activities stimulate angiogenesis and improved survival of
      tumor cells. How this large agenda can be achieved lies in the choice of Egr1
      target genes, and varying patterns of coordinated expression have been described,
      but the mechanisms for this choice are not clear. This review points to areas
      where research should be focussed.

PMID- 12065849
TI  - Colour-coded mapping technique in impression cytology - findings in soft contact
      lens wearers and patients with other external eye diseases.
AB  - This study aimed to demonstrate metaplastic changes in a wide area of
      conjunctival epithelium using the mapping technique by colouring different stages
      of metaplastic changes after marking them on a millimetric scale paper under a
      light microscope. Data of 23 patients were studied: 19 contact lens wearers, 2
      cases with dry eyes, 1 with lagophthalmus, 1 with conjunctivitis, and 13 normal
      subjects as controls. Cellulose acetate paper cut into crescents was applied to
      nasal and temporal quadrants of the conjunctiva. After evaluating the collected
      cells under light microscopy, they were marked on a millimetric scale. Almost all
      the patients had varying degrees of squamous metaplasia; however, significant
      differences were observed in the distribution and the percentage ratio of these
      changes. In conclusion the colour-coded mapping method yields valuable
      information in a broader perspective for determining the distribution and degree
      of the ocular surface changes caused by different physiological and pathological
      circumstances.

PMID- 12065850
TI  - Correlation between the retinal nerve fiber layer thickness and the pattern
      electroretinogram amplitude.
AB  - OBJECTIVE: To establish a correlation between the retinal nerve fiber layer
      (RNFL) thickness measured by a scanning laser polarimeter (GDx) and the pattern
      electroretinogram (p-ERG) amplitudes in a heterogeneous population sample
      composed of normal subjects, ocular hypertensive and glaucomatous patients.
      METHODS: 112 subjects were considered: 40 glaucomatous patients, 39 ocular
      hypertensive and 33 normal subjects. All were examined with the GDx, and the RNFL
      thickness was measured. A transient p-ERG was then recorded. RESULTS: A
      statistically significant correlation was observed between the RNFL thickness and
      the p-ERG amplitudes (p < 0.001) by means of linear regression analysis.
      CONCLUSION: We observed a strict correlation between the measurements of the RNFL
      thickness obtained with the GDx and the amplitude of the p-ERG signal. These
      techniques represent additional objective tools to detect an early glaucomatous
      damage.

PMID- 12065848
TI  - Photochemical internalisation: a novel drug delivery system.
AB  - The present report reviews a number of recently published papers on a novel
      technology for the cytosolic delivery of macromolecules named photochemical
      internalisation (PCI). PCI is based upon the light activation of a drug (a
      photosensitizer) specifically located in the membrane of endocytic vesicles.
      Light which is absorbed by the photosensitizer induces the formation of reactive
      oxygen species, of which singlet oxygen ((1)O(2)) is the predominant form.
      Singlet oxygen oxidizes biomolecules in the membranes of endosomes and lysosomes,
      resulting in a subsequent release of the contents of these compartments into the
      cytosol. Photosensitizers have a higher affinity for tumour tissues than for most
      normal tissues and are used in photodynamic therapy of various types of cancers.
      We have taken advantage of the PCI strategy to enhance the delivery of a variety
      of macromolecules, including ribosome-inactivating toxins, an immunotoxin, horse
      radish peroxidase, a ras peptide, RNA, oligonucleotides and protein encoding DNA,
      to the cytosol. Normally, a major intracellular barrier to the application of
      therapeutically interesting peptides and proteins or the application of DNA and
      RNA in gene therapy is the degradation of the macromolecules in the endocytic
      vesicles after uptake by endocytosis. Therefore, a photochemically induced
      rupture of endocytic vesicles and the subsequent cytosolic release of the
      macromolecules aids these molecules in escaping attack by the lysosomal
      hydrolases, thereby maintaining their biological activity. Thus, PCI represents a
      novel principle for the cytosolic delivery of biologically active macromolecules
      which overcomes the pivotal intracellular barrier of endosomes and lysosomes. In
      addition to being utilised as a new site-specific cancer therapy method, PCI can
      also be applied as a research tool for macromolecule delivery both in vitro and
      in vivo.

PMID- 12065852
TI  - Comparison of the effectiveness of scanning laser polarimetry and optical
      coherence tomography for estimating optic nerve fibre layer thickness in patients
      with glaucoma.
AB  - PURPOSE: The effectiveness of scanning laser polarimetry (by the nerve fibre
      analyser, NFA) and of optical coherence tomography (OCT) in estimating nerve
      fibre layer thickness (NFLT) and the correlations between NFLT and cup-to-disc
      (C/D) ratio or values of mean deviation (MD) from static visual field tests were
      compared using patients with glaucoma. MATERIALS AND METHODS: Twenty-four eyes
      from 24 glaucoma patients were enrolled. The NFLT was measured along a circle
      with a diameter 1.5 times that of the optic disc around the optic disc. The
      averaged estimated NFLT of the circle or of each quadrantal NFLT (nasal,
      temporal, superior, inferior) was compared. RESULTS: The co-variant indexes
      measured by the NFA were significantly smaller than those measured by OCT in both
      the averaged NFLT (p = 0.0002) and in each quadrantal NFLT (p < 0.05). The C/D
      ratio was significantly correlated with the averaged NFLT when measured by OCT (r
      = 0.425, p = 0.038), but not by the NFA (r = 0.179, p = 0.407). However, when
      measured by OCT, these values showed a significant correlation (r = 0.425, p =
      0.039). Although both the OCT and NFA data showed significant correlations
      between NFLT and the MD (p = 0.0002 and p = 0.038, respectively), the OCT data
      showed a stronger correlation than did the NFA data (r = 0.677 and r = 0.422,
      respectively). The correlation between the averaged NFLTs obtained by NFA and OCT
      was not significant (r = 0.289, p = 0.172). CONCLUSION: OCT is thought to have an
      equal or better effectiveness for estimating NFLT, in spite of a lower
      reproducibility than that of the NFA.

PMID- 12065851
TI  - Pattern visual evoked cortical potentials predict postoperative visual acuity
      after cataract surgery in patients with glaucoma.
AB  - Visual acuity after cataract surgery in patients with glaucoma cannot be
      predicted accurately. We studied preoperative recordings of pattern visual evoked
      cortical potentials (PVECPs) to evaluate postoperative vision in patients with
      glaucoma and cataract. Fifty patients with glaucoma and no cataract and 31
      patients with glaucoma and cataract who underwent phacoemulsification were
      included in this study. Age and P100 component significantly correlated with
      postoperative visual acuity with multiple linear regression analysis. A
      significantly greater number of patients with glaucoma, cataract, and a P100
      component preoperatively showed a visual acuity of 0.7 or better postoperatively,
      as compared to those without a P100 component. PVECP before cataract surgery was
      able to predict postoperative good visual acuity in patients with glaucoma and
      cataract.

PMID- 12065853
TI  - Ocular surface changes induced by topical antiglaucoma monotherapy.
AB  - PURPOSE: To investigate the expression of inflammatory markers HLA-DR in
      impression cytology specimens from patients receiving topical antiglaucoma
      monotherapy. METHODS: Impression cytology specimens were obtained from patients
      taking no topical medication (n = 13) and from primary open-angle glaucoma or
      ocular hypertensive patients taking one topical medication for at least 3 months
      (latanoprost n = 14; betaxolol n = 12; timolol n = 14). None of the patients had
      any signs of ocular surface inflammation as detected by slit-lamp examination, a
      normal Schirmer's test and tear breakup time. The expression of HLA-DR on
      epithelial cells and T lymphocytes was analysed by flow cytometry. RESULTS: A
      significant increase in HLA-DR on epithelial cells in patients on monotherapy was
      detected (latanoprost p < 0.05; betaxolol p < 0.01; timolol p < 0.01). Although
      the duration of treatment differed significantly between individual groups, there
      was no significant correlation between the length of monotherapy and the
      expression of inflammatory markers by epithelial cells and T lymphocytes. In the
      latanoprost group, the increased expression of HLA-DR was associated with a
      shorter duration of treatment. CONCLUSIONS: The flow-cytometric results indicate
      that administration of a single topical medication preserved with benzalkonium
      chloride, irrespective of type, for 3 months or more induced a significant degree
      of subclinical inflammation detected as increased expression of HLA-DR on
      conjunctival epithelial cells.

PMID- 12065854
TI  - Normal-tension glaucoma is associated with sleep apnea syndrome.
AB  - INTRODUCTION: In normal-tension glaucoma, optic nerve damage occurs without
      elevated intraocular pressures, hence vascular and pathogenic mechanisms other
      than intraocular pressure effects have been postulated. However, the exact
      cause(s) remain unknown. We have looked for an association between normal-tension
      glaucoma and sleep apnea syndrome, a disease characterized by repetitive upper
      airway obstructions during sleep, inducing hypoxia and sleep disruption with the
      risk of late cardiovascular and neurological sequelae. METHODS: We performed
      overnight polysomnography in 16 consecutive Caucasian patients with normal
      tension glaucoma. The respiratory disturbance index (RDI) during night sleep was
      used to diagnose and grade obstructive sleep apnea. Patients with an RDI of 10 or
      more were diagnosed as having obstructive sleep apnea. RESULTS: We observed the
      following prevalences of obstructive sleep apnea in normal-tension glaucoma
      patients: 0% (0 of 2) for the group of patients younger than 45 years, 50% (3 of
      6) for the age group 45-64 years, and 63% (5 of 8) for the group older than 64
      years. Prevalences in the middle and older age group were significantly higher
      than in a historic control group (p < 0.025 for both, binomial test). CONCLUSION:
      Normal-tension glaucoma patients constitute a high-risk population for sleep
      apnea syndrome. Therefore, they should be screened for sleep apnea syndrome, and,
      if necessary, be treated to avoid late cardiovascular and neurological sequelae.

PMID- 12065855
TI  - Correlation between contrast sensitivity and visual acuity in retinitis
      pigmentosa patients.
AB  - PURPOSE: High-contrast figures such as Landolt rings are insufficient to evaluate
      the function of the foveal cones of retinitis pigmentosa (RP) patients. We
      investigated the correlation between visual function as determined with Landolt
      rings and with the Vistech Contrast Sensitivity Function Test (VCTS) at various
      spatial frequencies, in addition to the Cambridge Low Contrast Grating (CLCG).
      METHODS: The study included 30 retinitis pigmentosa patients (53 eyes). All
      patients were assessed with Landolt rings, the Vistech method, and the CLCG. We
      estimated the relative contribution of contrast sensitivity to visual acuity by
      VCTS at each spatial frequency and by CLCG by simple linear regression analysis.
      RESULTS: The results of the regression analysis of VCTS at 1.5, 3.0, and 6.0
      cycles/degree showed a significant correlation between Landolt rings and VCTS and
      between CLCG and VCTS that was strongest at 6.0 cycles/degree. There was no
      significant correlation between Landolt rings and VCTS or between CLCG and VCTS
      at 12.0 and 18.0 cycles/degree. Patients with a visual acuity of 20/25 and CLCG
      greater than 100 were divided into two groups according to their contrast
      sensitivity at 18.0 cycles/degree on VCTS. CONCLUSIONS: The VCTS at the highest
      frequency was useful for evaluating the foveal visual function in RP patients
      having good visual acuity with the Landolt rings. Thus, contrast sensitivity
      should be useful in detecting minute impairment or improvement of visual function
      in RP.

PMID- 12065856
TI  - Management of retained intravitreal lens fragments after phacoemulsification
      surgery.
AB  - PURPOSE: To evaluate the clinical features of eyes with retained intravitreal
      lens fragments after phacoemulsification surgery and to assess the guidelines of
      management and the visual outcome after vitrectomy. METHODS: Twenty-five
      consecutive patients referred to our institute for retained intravitreal lens
      fragments after phacoemulsification cataract surgery were evaluated
      retrospectively over a 7-year period. RESULTS: The clinical features of retained
      lens fragments included deceased visual acuity of 6/60 or worse (68%), uveitis
      (60%), glaucoma (48%), corneal edema (44%) and retinal detachment in 2 patients
      (8%). There were 24 patients who underwent pars plana vitrectomy; 1 patient was
      managed with medical therapy. After vitrectomy, 17 eyes (71%) showed visual
      improvement, and final visual acuity was 6/12 or better in 13 eyes (54%). The
      causes of poor final visual outcome of 6/60 or worse included retinal detachment
      and cystoid macular edema. The time interval between vitrectomy and
      phacoemulsification was within 4 weeks in 17 patients (71%), ranging from on the
      same day to 97 days. There was only a trend of better visual outcome in early
      vitrectomy patients (within 1 week). There was no statistical difference between
      the initial intraocular lens status and final visual acuity. CONCLUSION:
      Vitectomy with removal of retained intravitreal lens fragments is beneficial for
      patients with persistent uveitis and glaucoma after phacoemulsification. In the
      majority of patients, visual improvement was achieved after vitrectomy. However,
      poor visual outcome may occur secondary to retinal detachment and cystoid macular
      edema.

PMID- 12065857
TI  - Results of autografting of marginal conjunctiva in pterygium excision.
AB  - PURPOSE: To investigate and compare the efficiency of autografting of marginal
      conjunctiva (autograft of marginal conjunctiva technique, AMCT) and the bare
      sclera technique (BST) in pterygium excision. MATERIALS AND METHODS: In this
      study, 51 eyes of 51 patients who underwent pterygium surgery using the AMCT
      (group 1) were compared to 45 eyes of 45 patients who underwent pterygium
      excision using the BST (group 2), with regard to epithelialisation, recurrence
      and complication of the procedures. Patients were followed up for 15.37 +/- 12.01
      months in group 1 and for 18.57 +/- 10.42 months in group 2. RESULTS:
      Postoperative epithelialisation was completed in 4.34 +/- 1.27 days in group 1
      and in 5.61 +/- 1.71 days in group 2. Epithelialisation was completed earlier in
      group 1 than group 2 (p < 0.05). Recurrences were detected in 7 eyes (13.73%) of
      group 1 and in 17 eyes (37.78%) of group 2. The difference between the groups was
      statistically significant (p < 0.01). No postoperative complications were seen in
      either of the groups. CONCLUSIONS: The AMCT was found to be a more efficient
      procedure than the BST. Autografting of marginal conjunctiva may be a useful
      alternative treatment in pterygium surgery due to higher success and lower
      recurrence rates.

PMID- 12065858
TI  - ICAM-1 expression on the surface of T lymphocytes in patients with uveitis: a
      comparative study between the eye and peripheral blood.
AB  - PURPOSE: We studied the surface expression of intracellular adhesion molecule 1
      (ICAM-1) on peripheral and intra-ocular T lymphocytes in patients with active
      uveitis. METHODS: Two-colour flow-cytometric analysis was performed on cells
      isolated from aqueous humour and peripheral blood of 23 patients with active
      uveitis and 16 control patients who were to undergo cataract extraction, in order
      to determine the percentage of cells expressing CD4, CD8 and ICAM-1 (CD54)
      molecules. RESULTS: In the aqueous humour of patients with uveitis, we found an
      increase in the percentage of CD4+ and CD8+ lymphocytes, co-expressing the ICAM-1
      molecule as compared to control patients (p < 0.0001). In peripheral blood, these
      uveitis patients exhibited a significant decrease in the percentage of CD4+ICAM
      1+ (p = 0.0106) and CD8+ICAM-1+ (p = 0.0014) as compared to control subjects. The
      comparative study of cells from the aqueous humour and peripheral blood showed
      that the percentage of CD4+ICAM-1+ cells was higher in the aqueous humour (p <
      0.0001). Comparison of the aqueous humour and peripheral blood for CD8+ICAM-1+
      cells revealed no significant differences. In addition, we found a high negative
      correlation for the CD8+ICAM-1+ subset between the aqueous humour and peripheral
      blood. CONCLUSIONS: Our results suggest a greater local participation for
      CD4+ICAM-1+ cells but not for CD8+ICAM-1+ cells in the pathogenesis of uveitis.

PMID- 12065859
TI  - Detection of inducible nitric oxide synthase and vascular endothelial growth
      factor in choroidal neovascular membranes.
AB  - Vascular endothelial growth factor (VEGF) is among the cytokines which have been
      implicated in the pathogenesis of choroidal neovascularization secondary to age
      related macular degeneration (ARMD). There is, however, evidence that
      intercellular signaling molecules, such as nitric oxide (NO), are involved in
      this process. NO is synthesized via the inducible isoform of NO synthase (iNOS),
      which is expressed after induction by cytokines. In the current study, we
      investigated whether VEGF and iNOS are coexpressed in choroidal neovascular
      membranes (n = 7) from patients with ARMD. Immunohistochemistry was performed on
      cryosections with anti-iNOS and anti-VEGF. Moderate to intense immunostaining for
      iNOS and VEGF was observed in retinal pigment epithelial cells, macrophages, and
      in spatial relation to vessel walls. As scored by light microscopy, we found a
      significant correlation between immunoreactivity for VEGF and iNOS (p < 0.0341)
      in vascular endothelial cells. Our study supports a significant role for iNOS in
      the pathogenesis of neovascularization and membrane growth in ARMD. Moreover, our
      findings suggest a possible relationship between NO and VEGF in the regulation of
      pathologic angiogenesis in this disease.

PMID- 12065860
TI  - Chlamydia in anterior ischemic optic neuropathy.
AB  - There is an increasing body of evidence linking the common respiratory human
      pathogen Chlamydia pneumoniae with atherosclerosis and other vascular disorders.
      Our research was designed to investigate the association of this organism with
      anterior ischemic optic neuropathy (AION), representing an acute ischemic
      disorder of the optic nerve head. Sera were examined of 14 consecutive patients
      with AION and of 14 age- and sex-matched control subjects with noncardiovascular,
      nonpulmonary disorders. Antibodies against chlamydial lipopolysaccharide (LPS)
      and outer membrane proteins of C. pneumoniae were determined by ELISA. Further,
      nucleic acid amplification tests were done in order to detect C. pneumoniae
      specific nucleotide sequences. Four patients (29%) were IgA positive, 11 (79%)
      were IgG positive and 1 (7%) was IgM positive for chlamydial LPS antibodies. In
      the control group, 36, 79 and 7% were IgA, IgG and IgM positive and showed no
      significant difference. IgA, IgG and IgM antibodies to C. pneumoniae were found
      in 43, 79 and 0% and did not differ from matched controls. By the nucleic acid
      amplification test, specific C. pneumo niae sequences were neither detected in
      the AION patients nor in the control group. These data do not support the
      association of AION with previous C. pneumoniae infection. However, it remains
      unclear whether Chlamydia actually initiates atherosclerotic injury, facilitates
      its progression or plays another role in other vascular disorders.

PMID- 12065862
TI  - Three cases of a rare congenital abnormality of the retinal pigment epithelium:
      torpedo maculopathy.

PMID- 12065861
TI  - Optic disk vasculitis associated with chronic active Epstein-Barr virus
      infection.
AB  - PURPOSE: To report two cases of optic disk vasculitis associated with chronic
      active Epstein-Barr virus infection (CAEBV). METHOD: We examined the eyes of two
      patients with CAEBV. RESULTS: In the first case, a 6-year-old boy, visual acuity
      was 20/20 in both eyes. Papillary and peripapillary exudates were observed in the
      right eye. Fluorescein angiography showed hyperfluorescence of the optic disk and
      a leakage from the peripapillary retinal vessels in the right eye. Two months
      later, the exudates increased and preretinal hemorrhages appeared in the right
      eye. Visual acuity decreased to 20/60. He was treated with systemic
      administration of corticosteroid, globulin and acyclovir. Visual acuity returned
      to 20/20, but peripapillary exudates remained in the right eye. In the second
      case, a 16-year-old girl, visual acuity was 20/20 in both eyes. The right eye
      showed optic disk swelling and dilated retinal veins. Fluorescein angiography
      showed hyperfluorescence of the optic disk but no leakage from the retinal
      vessels. Visual field examination revealed an enlarged blind spot in the right
      eye in both cases. These ocular manifestations are compatible with those of optic
      disk vasculitis, which shows swelling of the optic disk and dye leakage on and
      around the optic disk in fluorescein angiography, with an almost normal visual
      acuity and an enlargement of the blind spot. CONCLUSION: Persistent Epstein-Barr
      virus infection may cause optic disk vasculitis.

PMID- 12065863
TI  - Bilateral leopard spot fundus of hypertensive choroidopathy and its visual
      function.

PMID- 12065865
TI  - Vaccination strategies in the treatment of lymphomas.
AB  - Malignant lymphomas are clonal neoplasms of lymphoid origin. By definition, all
      cells of the malignant clone have undergone the same rearrangement of antigen
      receptor genes and express identical antigen receptor molecules (immunoglobulin
      for B cell lymphomas, T cell receptor for T cell lymphomas). The hypervariable
      stretches within the variable regions of these receptors are considered true
      tumor-specific antigens ('idiotypes'). In several animal models, protective
      humoral or cellular immunity can be induced against the malignant lymphoma by
      vaccination with the tumor-derived idiotype. Successful experimental immunization
      strategies in animals include idiotype protein vaccines combined with various
      adjuvants, genetically or immunologically modified lymphoma cells, idiotype
      presenting dendritic cells, idiotype-encoding viral vectors, and DNA
      immunization. Firm evidence for the induction of lymphoma-specific immunity has
      also been obtained from human idiotype vaccination trials. Furthermore, some
      trials have provided strong but hitherto formally unproven evidence for clinical
      benefit of idiotype-vaccinated patients. Alternative vaccination approaches are
      based on immunologically modified tumor cells. Current research efforts
      concentrate on the identification of the most efficacious vaccination route, on
      definitive proof of clinical efficacy, and on the development of convenient
      methods to manufacture individual idiotype vaccines.

PMID- 12065866
TI  - Evaluation of intraoperative intraperitoneal cytology for advanced gastric
      carcinoma.
AB  - OBJECTIVE: We evaluated intraperitoneal cytology during surgery as a significant
      predictor of survival and tried to establish strategies for preventing peritoneal
      carcinomatosis. METHODS: The study included 236 patients with gastric carcinoma
      macroscopically invading the serosa who underwent intraperitoneal cytological
      examination during surgery. In the 215 resected patients, the relationship
      between cytological positivity for cancer cells and various clinicopathologic
      features was analyzed. Additionally, postoperative survival was assessed in
      relation to the positivity of intraoperative cytology. RESULTS: Cancer cells were
      positive [Cy+] in 78 (33.1%) of 236 patients who underwent cytological
      examinations. Among 73 patients with peritoneal metastases, 53 patients (72.6%)
      were Cy+, as were 25 (15.3%) of the 163 patients without peritoneal metastases.
      Multivariate analysis indicated that peritoneal metastasis (p = 0.0001) and the
      depth of tumor invasion (p = 0.0069) were significant factors correlated with
      Cy+. Among patients with curative surgery, the 5-year survival rate of the Cy+
      group was 22.2%, which was worse (p = 0.0004) compared with that of the Cy(-)
      group (60.9%). Among Cy+ patients, the survival rate of the group treated with
      intraperitoneal administration of mitomycin C (MMC) and OK-432 was better (p =
      0.0108) than that of the historical control group. CONCLUSION: These results
      suggest that intraperitoneal cytological examination can be a significant
      prognostic factor for gastric carcinoma with serosal invasion. In addition,
      dissemination of cancer cells in the peritoneum may be controlled by
      intraperitoneal immunochemotherapy with MMC and OK-432.

PMID- 12065867
TI  - A phase II study of irinotecan alternated with a weekly schedule of high-dose
      leucovorin and 48-hour 5-fluorouracil infusion in patients with metastatic
      colorectal cancer.
AB  - PURPOSE: To evaluate the activity and safety of an alternating schedule of
      irinotecan (CPT-11) with high-dose 5-fluorouracil (5-FU) given as a weekly 48
      hour infusion in combination with leucovorin (LV) in the first-line treatment of
      metastatic colorectal cancer (MCRC) patients. PATIENTS AND METHODS: We tested the
      activity of a regimen consisting of a four times per week schedule of high-dose
      LV (150 mg/m2) followed by a 48-hour 5-FU infusion (2,600 mg/m2) alternated with
      CPT-11 (350 mg/m2). An alternating cycle was to be performed every 8 weeks.
      Treatment was administered until disease progression, unacceptable toxicity or
      patient refusal occurred. Thirty-five consecutive patients with measurable MCRC,
      aged 18-80, with a performance status < or =2, were entered into our study from
      May 1998 to January 2000. RESULTS: Four complete and 9 partial responses were
      observed (objective response rate was 37%; 95% confidence interval, CI: 21.5
      55.1%); an additional 46% of the patients had stable disease. The median duration
      of response was 6.2 months, median time to progression 8 months (95% CI: 5.9
      10.1%), and overall survival was 18.5 months (95% CI: 15.1-21.9%). The 1-year
      survival was 68%. No toxic deaths occurred. The incidence of grade 3-4 toxicity
      per patient in any cycle was: mucositis 9% and diarrhea 11% for the infusional 5
      FU part, nausea/vomiting 3%, diarrhea 14%, and neutropenia 43% for the CPT-11
      part of regimen. CONCLUSIONS: Our alternating schedule of 5-FU/LV and CPT-11 is a
      well-tolerated outpatient treatment as front-line therapy for MCRC with
      comparable efficacy to regimens with both drugs given together.

PMID- 12065868
TI  - Phase I study of paclitaxel (taxol) and pegylated liposomal doxorubicin (caelyx)
      administered every 2 weeks in patients with advanced solid tumors.
AB  - OBJECTIVES: Paclitaxel and doxorubicin are among the most active chemotherapeutic
      agents in various types of tumors. Pegylated liposomal doxorubicin (Caelyx) has a
      more favorable pharmacokinetic and toxicity profile than the free drug. We
      conducted a phase I study to determine the maximum tolerated doses (MTD) and the
      dose limiting toxicities (DLT) of the combination administered every 2 weeks in
      patients with advanced solid tumors. PATIENTS AND METHODS: Treatment consisted of
      escalating doses of Caelyx (12.5-17.5 mg/m2) administered as a 30-min intravenous
      infusion on day 1 and paclitaxel (90-115 mg/m2) as a 3-hour intravenous infusion
      on day 2 every 2 weeks without growth factor support. One cycle was considered as
      the administration of two consecutive treatments in 28 days. Twenty-six patients
      with histologically confirmed advanced stage solid tumors have been enrolled.
      Treatment was first-line treatment for 38% of patients, second-line for 31% and
      third-line for 31%. RESULTS: The DLT were evaluated during the first 4 weeks of
      treatment (2 treatment administrations) and consisted in all but one case of
      grade 2-3 neutropenia resulting in treatment delay. One patient died of cardiac
      arrest 1 day after the first treatment. A total of 86 cycles have been
      administered with only 1 episode of febrile neutropenia. Hematologic toxicity was
      generally mild. Only 1 patient at the first and another at the highest dose level
      developed grade 4 neutropenia. At the highest dose level, 3 of 6 patients
      developed grade 3 neutropenia. Grade 4 anemia or grade 3-4 thrombocytopenia was
      not observed. Non-hematologic toxicity included grade 2-3 nausea/vomiting in 10%,
      grade 2-4 diarrhea in 7% and grade 2-3 neurotoxicity in 8% of cycles. Mucositis
      grade 3 complicated 1 cycle. Palmar-plantar erythrodysesthesia grade 2-3 was
      observed in 3 patients and was the reason for treatment discontinuation in 1
      patient. Cardiotoxicity as the development of congestive heart failure or more
      than 10% reduction in left ventricular ejection fraction was not observed. The
      most common non-hematologic toxicity was grade 2-3 asthenia complicating 31% of
      the cycles. Among 18 evaluable patients, 1 complete and 4 partial responses were
      observed primarily in patients with breast cancer. The MTD which are the
      recommended doses for further use in phase II trials were Caelyx 15 mg/m2 on day
      1 and paclitaxel 115 mg/m2 on day 2 administered every 2 weeks. CONCLUSION: The
      administration of Caelyx and paclitaxel every 2 weeks is a feasible regimen and
      is associated with acceptable toxicity.

PMID- 12065869
TI  - Phase II study of uracil-tegafur in patients with metastatic pancreatic cancer.
AB  - OBJECTIVE: Uracil-tegafur (UFT) has been reported to have a broad anti-tumor
      activity in a variety of malignancies including colorectal cancer and breast
      cancer. However, its activity in pancreatic cancer has not been fully evaluated.
      The aim of the present study was to evaluate the anti-tumor activity and toxicity
      of UFT in patients with metastatic pancreatic cancer. METHODS: All patients were
      required to have a pathologic diagnosis of pancreatic adenocarcinoma with
      measurable metastatic lesions, and no prior chemotherapy. A dose of 360 mg/m2/day
      of UFT was administered orally until the appearance of disease progression or
      unacceptable toxicity. RESULTS: Twenty-two patients were entered into this study.
      Of 21 patients evaluable for response, no patient achieved an objective tumor
      response; one showed no change, and the remaining 20 showed progressive disease.
      The median survival time for all patients was 4.2 (range: 0.9-9.0) months. The
      most common toxicities were nausea/vomiting and anorexia. Five patients (23%) had
      to discontinue UFT treatment because of gastrointestinal toxicity. CONCLUSION:
      This schedule of UFT did not demonstrate a significant anti-tumor activity
      against metastatic pancreatic cancer.

PMID- 12065870
TI  - Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular
      carcinoma.
AB  - Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic
      agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter
      arterial infusion chemotherapy using SMANCS for HCC showed a response rate of
      20%. In an effort to obtain a superior anti-tumor effect against HCC, we
      conducted a phase II study of transcatheter arterial embolization (TAE) using
      SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four
      milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic
      artery, followed by an injection of gelatin sponge. The responses were evaluated
      by computed tomography (CT) 1 month after treatment and thereafter every 3-4
      months. One patient (2%) showed complete response and 15 patients (30%) had
      partial response resulting in an overall response rate of 32% (16/50; 95%
      confidence interval 19-45%). In 33 patients (66%), the disease remained stable,
      and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of
      necrotic area to whole tumor was more than 50% according to the evaluation method
      using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90,
      55 and 19%, respectively. Grade 3 hematological toxicity was observed as
      thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity
      (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE
      using SMANCS, which was well tolerated, may be an effective treatment for
      advanced HCC.

PMID- 12065871
TI  - Prognostic evaluation of preoperative thermochemoradiotherapy for N(3) cervical
      lymph node metastases of oral cancer.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy,
      histopathological efficacy, and response to preoperative thermochemoradiotherapy
      for N(3) cervical lymph node metastases of oral cancer. METHODS: Preoperative
      thermochemoradiotherapy was performed in 8 patients with oral cancer and N(3)
      cervical lymph node metastasis. These patients underwent four-weekly sessions of
      hyperthermia, combined with radiotherapy (40 Gy) as well as chemotherapy with
      cisplatin (CDDP; 100 mg/m2), all prior to surgery. Radical neck dissection was
      performed 4 weeks after completion of preoperative thermochemoradiotherapy.
      RESULTS: The preoperative treatment of cervical lymph node metastases yielded a
      partial response in 6 patients, while 2 patients demonstrated no change.
      Histopathologically, grade III was detected in 1, grade IIb in 4 and grade IIa in
      3 patients after surgery, according to the criteria of Shimosato. The follow-up
      period ranged from 13 to 64 months (mean 34). Of the 8 patients, 2 died (1 of
      lymph node metastasis and 1 had metastasis to a distant site), and 6 patients
      were alive at the last follow-up, with the longest postoperative disease-free
      survival being 63 months. The 5-year cumulative survival rate was 70.0%.
      CONCLUSION: These results indicate that preoperative thermochemoradiotherapy is a
      promising modality for patients with N(3) cervical lymph node metastasis of oral
      cancer.

PMID- 12065872
TI  - DNA sequences of the immunoglobulin heavy chain variable region gene in pyothorax
      associated lymphoma.
AB  - B cell lymphoma develops in the pleural cavity of patients affected by long
      standing pyothorax resulting from lung tuberculosis, thus termed pyothorax
      associated lymphoma (PAL). PAL usually shows a diffuse large cell morphology, and
      constantly contains Epstein-Barr virus (EBV) genome. To investigate whether PAL
      cells proliferate in response to specific antigenic stimuli and its stage in B
      cell differentiation, immunoglobulin heavy chain gene in 7 cases and 2 cell lines
      from PAL, all confirmed by histological studies to be EBV-positive diffuse large
      B cell lymphoma, were examined by using polymerase chain reaction (PCR) method.
      Clonal rearrangement of the gene was detected in 4 cases of PAL tissues and one
      cell line. As for the usage of the V region gene (V(H)), the V(H)3 family gene
      was used in 3 of these 5 cases with different homologous germlines, suggesting
      that the origin of PAL cells from a repertoire of B lymphocytes responsive to
      specific antigenic epitope was unlikely. Compared to the homologous germline, the
      mutation frequency of PAL was 9% on average. Only one case might have more
      replacement mutations in the complementarity-determining regions than expected by
      chance, thus antigen-selected maturation might not take place in PAL. Intraclonal
      sequence heterogeneity in the V(H) gene was found in another case. From these
      findings, it is concluded that PAL is composed of B lymphocytes at the
      differentiation stage of the postgerminal center. Antigen-selected maturation
      might not take place in PAL, which is distinct from the majority of B cell
      lymphomas.

PMID- 12065873
TI  - Detection of genetic alterations in pancreatic cancers by comparative genomic
      hybridization coupled with tissue microdissection and degenerate oligonucleotide
      primed polymerase chain reaction.
AB  - The aim of this study was to elucidate cytogenetic changes in pancreatic cancers
      (PCs) and to examine their clinical implications. We screened for genetic
      alterations in 32 primary PCs including 4 cases with distant organ metastasis
      using comparative genomic hybridization coupled with tissue microdissection and
      degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR). The
      present study revealed frequent gains of chromosomes 13q and 15q and a loss of Xq
      in addition to a high prevalence of chromosomal imbalances. The average number of
      total genetic alterations and gains tended to be higher in N1 tumors (TNM
      classification) than in N0 tumors. The average number of amplifications was
      significantly higher in M1 tumors than in M0 tumors (p = 0.024).
      Gain/amplification of 20q was more frequently observed in M1 tumors than in M0
      tumors (p = 0.016), and this change was also detected in all of 4 distant
      metastatic lesions. Losses of 6q, 8p, 9p, 17p, and 18q were recurrent in N0 and
      M0 tumors, and these alterations were also retained in N1 and M1 tumors. These
      observations suggest that these genetic losses contribute to the development of
      PCs and that increases in the DNA copy number confer an aggressive character on
      cancer cells. Especially, gain/amplification of 20q was associated with the
      potential of distant organ metastasis of tumor cells.

PMID- 12065874
TI  - Immunohistochemically detectable bcl-2 expression in metastatic melanoma:
      association with survival and treatment response.
AB  - OBJECTIVE: The antiapoptotic protein Bcl-2 is supposed to influence the treatment
      responsiveness of different malignancies. In the present study the prognostic and
      predictive significance of Bcl-2 expression for survival and response to an
      administered therapy was explored in patients with metastatic melanoma. Also, the
      correlation between Bcl-2 expression and proliferation activity of tumor cells
      was defined to examine the regulatory role of Bcl-2 in proliferation. MATERIALS
      AND METHODS: Sixty metastatic melanomas obtained from patients treated with
      chemoimmunotherapy were examined by immunohistochemistry with anti-Bcl-2 and anti
      Ki-67 (MIB-1) antibodies. Proliferation activity was expressed in percentages as
      MIB-1 index. RESULTS: The presence of Bcl-2 immunoreactivity was associated with
      a significantly lower MIB-1 index (p = 0.016), and a longer disease-free survival
      (p = 0.004). The lack of Bcl-2 expression was related to a higher response rate
      to therapy in comparison to a diffuse and focal pattern of Bcl-2 expression (p =
      0.017). Although the presence of Bcl-2 immunoreactivity as such did not correlate
      with survival after the initiation of chemoimmunotherapy, the focal Bcl-2
      expression pattern was strongly associated with a worse prognosis compared to a
      diffuse expression or a lack of Bcl-2 staining (p < 0.0001). CONCLUSIONS: Our
      results support the role of Bcl-2 in the regulation of cell proliferation and
      suggest that an increase of metastatic potential and progression of malignant
      melanoma is associated with a loss of Bcl-2 expression. The lack of Bcl-2
      expression could be a predictor of the response to chemoimmunotherapy, whereas
      the Bcl-2 expression pattern, possibly indicating the heterogeneity of the
      tumors, might be a potential prognostic factor for survival after the initiation
      of therapy.

PMID- 12065875
TI  - Clinical implications of the expression of estrogen receptor-alpha and -beta in
      primary and metastatic lesions of uterine endometrial cancers.
AB  - Novel human estrogen receptor (ER)-beta was identified in cDNA libraries from
      human testes. ER-beta specifically expresses in the testis, ovary, thymus,
      spleen, osteoblasts, fetus and uterine endometrium. ER-beta might not conserve
      the same physiological functions as does ER-alpha. Therefore, expressions of ER
      alpha and ER-beta mRNAs in primary and metastatic lesions of uterine endometrial
      cancers were investigated. The levels of ER-beta mRNA were significantly lower
      than those of ER-alpha mRNA in uterine endometrial cancers and in normal uterine
      endometria. The ratio of ER-beta to ER-alpha mRNA in most primary uterine
      endometrial cancers was similar to that in normal uterine endometria (<0.4% of ER
      beta mRNA to ER-alpha mRNA). On the other hand, in 14 of the 20 lymph node
      metastasis-positive cases of uterine endometrial cancers, the ratio in the
      metastatic lesion was significantly higher than that in the primary lesion of the
      corresponding case, and patient prognosis in these cases was extremely poor.
      Therefore, it is suggested that the intact synchronized expression of ER-beta
      interacting with ER-alpha might be disrupted, especially in most metastases of
      uterine endometrial cancers, leading to poor patient prognosis related to
      estrogen refractoriness.

PMID- 12065876
TI  - mdm2-p53 Interaction: lack of correlation with the response to 5-fluorouracil in
      advanced colorectal cancer.
AB  - OBJECTIVE: We investigated the relevance of mdm2 and p53 primary tumour
      expression to the clinical outcome of a consecutive series of advanced colorectal
      cancer patients treated with a 5-fluorouracil-based chemotherapy. METHODS: The
      expression of p53 and mdm2 was analyzed by an immunohistochemical assay in 80
      formalin-fixed paraffin embedded primary tumour samples and related to the
      clinical response to 5-fluorouracil therapy and to the prognosis of the patients.
      In a subgroup of 46 tumours, the apoptotic index (AI) as determined by the Tunel
      technique was also assessed. RESULTS: Nuclear immunostaining of p53 and mdm2 was
      present in 42 and 30% of the cases, respectively. No correlation was demonstrated
      between p53 and mdm2 expression (rs = -0.01; p > 0.05). With regard to the
      clinical outcome, no statistical association was demonstrated among p53 and mdm2
      expression, AI, probability of clinical response to treatment, time to
      progression, or overall survival. The subgroup of patients with a p53
      negative/mdm2-positive tumour showed a worse response rate (15%); however, mdm2
      positive/AI-negative tumours showed a 0% (0/7) probability of a clinical response
      as compared with 30% (9/30) of the remaining tumour patient subgroups; this also
      translated in a significantly worse overall survival probability (p = 0.01 by log
      rank). CONCLUSIONS: The analysis of mdm2 expression does not add significant
      clinical information in colorectal cancers with a different p53 status.
      Conversely, further analysis of AI seems to give data of a promising prognostic
      predictive value.

PMID- 12065877
TI  - PAI-1 promoter polymorphism modulates uPA-PAI complex accumulation by breast
      cancer cells.
AB  - OBJECTIVES: The uPA-PAI system has been shown to play a role in the development
      of a more aggressive tumor phenotype. The PAI-1 promoter 4G/5G polymorphism,
      furthermore, regulates free plasma PAI-1 levels in patients with myocardial
      infarction. Our aim was to verify if the different polymorphisms in the PAI-1
      promoter are also associated with alterations in the intracellular accumulation
      of uPA-PAI complexes in human breast cancer. METHODS: Accumulation of uPA-PAI
      complexes inside the tumor cells was determined by means of immunohistochemistry,
      as previously described by our own group, and two extremely different sets of
      tumors were chosen, one of them with strong uPA-PAI complex reactivity inside
      more than 50% of tumor cells, the other with no demonstrable reactivity at all.
      Finally, the 4G/5G polymorphism of the PAI-1 promoter was studied in all of them
      by means of DNA extraction, PCR amplification of the PAI promoter sequence, and
      restriction polymorphism typing. RESULTS: Absence of intracellular uPA-PAI
      complex accumulation was significantly associated with the prevalence of the 4G
      allele and, conversely, the presence of uPA-PAI complexes inside the tumor cells
      was significantly associated with 5G/5G homozygosity (logistic regression, p =
      0.0128). Furthermore, none of the 7 5G/5G homozygous tumors showed histological
      grade 3, as did 6/21 tumors in the group where the 4G allele was present. In
      spite of the low case number, this association of the 5G/5G polymorphism with a
      less aggressive phenotype almost reached statistical significance (Spearman's
      correlation test, p = 0.118). CONCLUSIONS: The 4G/5G polymorphism of the PAI-1
      promoter seems indeed to be associated with different rates of uPA-PAI complex
      internalization by breast cancer cells. Complex accumulation inside the tumor
      cells is significantly related to 5G/5G homozygosity, and this shows a trend
      towards an association with a less aggressive, better-differentiated tumor
      phenotype.

PMID- 12065878
TI  - Return to work after ischemic stroke: a methodological review.
AB  - Despite the economic cost of lost employment, return to work after ischemic
      stroke has received little study. The percentages of patients working after
      stroke vary widely from 11 to 85%. Comparisons of these studies are difficult
      because they report return to work in different populations after diverse follow
      up periods using variable definitions of stroke and work. Stroke severity as
      measured by activities of daily living was the most robust predictor of return to
      work. However, many factors known to influence vocational outcome after other
      illness (e.g., social and job characteristics) have not been examined. Directions
      for future studies of return to work are suggested.

PMID- 12065879
TI  - Distribution of multiple sclerosis in Sweden based on mortality and disability
      compensation statistics.
AB  - Previous studies have shown the Fennoscandian region to be a high-risk area for
      multiple sclerosis (MS). In order to investigate the distribution of MS in
      Sweden, mortality (1952-1992) and disability pensioning statistics (1971-1994)
      were studied. A total of 11,414 cases with a disability pension and 5,421 cases
      with MS on their death certificate were analysed according to county and time
      period and the results were compared with the mortality figures for amyotrophic
      lateral sclerosis (ALS) and disability pensioning statistics for Parkinson's
      disease. We found increasing rates of both MS mortality and disability
      pensioning. Disability pensioning correlated well with mortality 10 years later
      (r = 0.42, p = 0.04). We also found a marked geographical variation. Varmland
      county had the highest mortality, with 14 out of its 16 municipalities having
      higher rates than the national mean. Unexpectedly, we found a high correlation
      between mortality due to MS and ALS (r = 0.60, p = 0.002).

PMID- 12065880
TI  - Hepatitis B vaccination and first central nervous system demyelinating event: a
      case-control study.
AB  - OBJECTIVE: To investigate the relationship between hepatitis B (HB) vaccination
      and a first central nervous system (CNS) demyelinating event in adults. METHODS:
      In 1998, we conducted a multicentre, hospital-based case-control study which
      enrolled 402 cases of first CNS demyelinating event occurring between 1994 and
      1995 and 722 controls matched for centre, age, sex and date of admission. An
      independent expert committee validated the diagnoses of cases and controls. Data
      on vaccinations were obtained from a standardized phone interview. Forty percent
      of eligible cases and 50% of eligible controls could not be localized or were
      excluded because they did not satisfy inclusion or matching criteria. RESULTS:
      Conditional logistic regression performed on 236 and 355 matched controls showed
      that adjusted odds ratios for the first CNS demyelinating event within 2 months
      following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7
      4.6] in the whole group and 1.4 (95% CI, 0.4-4.5) in the subgroup of cases (n =
      152) and controls (n = 253) referring to vaccination certificates during the
      phone interview. Restricting the analyses to the cases with definite or probable
      multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8-5.4) and 1.6 (95% CI,
      0.4-5.6), respectively. Odds ratios tend towards 1 for a longer interval between
      HB vaccine and demyelinating event. CONCLUSIONS: This study was sufficiently
      powerful to rule out a strong association between HB vaccine exposure and a
      subsequent demyelinating event. However, it could not provide a clear indication
      of a moderately increased risk of a CNS demyelinating event shortly after HB
      vaccination in adults.

PMID- 12065881
TI  - An ecologic study of geographical variation in multiple sclerosis risk in central
      Sardinia, Italy.
AB  - We carried out an ecological study in the most archaic area of Sardinia to obtain
      a reliable estimate of the prevalence of multiple sclerosis (MS) and to
      investigate the geographical variation in the prevalence across the 100
      administrative communes. To estimate the area-specific prevalence rate, we
      adopted a Bayesian approach that makes it possible to filter out the random
      variation from the estimates and to obtain a map that reflects the true
      geographical variation in MS prevalence. 428 resident cases were identified by
      the case register, including 69 multiplex families. The overall prevalence was
      157 per 100,000 inhabitants. The Bayesian area-specific prevalence ranged from
      143 to 262/100,000. The high prevalence and its moderate geographical variation
      in a genetically homogeneous population, as well as the high number of multiplex
      families observed in the communes with the highest prevalence, could be
      interpreted as representing a high susceptibility of the population to MS.

PMID- 12065882
TI  - The Maracaibo Aging Study: population and methodological issues.
AB  - The Maracaibo Aging Study is a longitudinal, population-based, one-step
      multidisciplinary study of age-related diseases, with a particular focus on
      memory-related disorders, among subjects over 55 years living in a neighborhood
      of the city of Maracaibo, Venezuela. Three phases were scheduled for this study.
      First, a door-to-door survey was conducted in order to build a registry and to
      obtain general and sociodemographic characteristics. During the second phase,
      information regarding changes in the abilities of the subjects was collected. The
      third phase consisted of a full neuropsychiatric examination, cardiovascular
      evaluation, nutritional assessment, neuropsychological testing, routine
      laboratory tests and genetic analysis. 3,657 subjects were surveyed between
      January and August, 1998. There were more women than men, and the average number
      of years of formal education was low, particularly among women. The limitations
      and strengths of the study are discussed.

PMID- 12065883
TI  - Service-based survey of dystonia in munich.
AB  - We performed a service-based epidemiological study of dystonia in Munich,
      Germany. Due to favourable referral and treatment patterns in the Munich area, we
      could provide confident data from dystonia patients seeking botulinum toxin
      treatment. A total of 230 patients were ascertained, of whom 188 had primary
      dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence
      interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised
      primary dystonia. The most common focal primary dystonias were cervical dystonia
      with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000
      followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per
      100,000.

PMID- 12065884
TI  - Sex ratios of affected and unaffected offspring of male and female patients with
      multiple sclerosis.

PMID- 12065886
TI  - Somatostatin receptor subtypes 2 and 5 inhibit corticotropin-releasing hormone
      stimulated adrenocorticotropin secretion from AtT-20 cells.
AB  - Somatostatin (SRIH) regulates pituitary adrenocorticotropin (ACTH) secretion by
      interacting with a family of homologous G protein-coupled membrane receptors. The
      SRIH receptor subtypes (sst(1)-sst(5)) that control ACTH release remain unknown.
      Using novel, subtype-selective SRIH analogs, we have identified the SRIH receptor
      subtypes involved in regulating ACTH release from AtT-20 cells, a model for cell
      line pituitary corticotropes. Radioligand-binding studies with (125)I-SRIH-14 and
      (125)I-SRIH-28 showed that SRIH-14 and SRIH-28 recognized specific, high-affinity
      and saturable membrane-binding sites. Nonpeptidyl agonists with selectivity for
      the sst(2) (L-779,976; compound 2) or sst(1)/sst(5)) (L-817,818; compound 5)
      receptor subtypes potently displaced (125)I-SRIH-28 from AtT-20 cell membranes,
      while agonists selective for the sst(1) (L-779,591; compound 1), sst(3) (L
      796,778; compound 3) or sst(4) (L-803,087; compound 4) subtypes were inactive.
      Tyr(11)-SRIH-14, compound 2 (sst(2)) or compound 5 (sst(5)) inhibited forskolin
      and corticotropin-releasing hormone (CRH)-induced increases in intracellular
      cAMP. Furthermore, the sst(2) and sst(5) agonists potently inhibited CRH-induced
      ACTH release from AtT-20 cells. These results provide the first evidence that
      sst(2) and sst(5) receptor subtypes, but not sst(1), sst(3) or sst(4), inhibit
      cAMP accumulation and regulate ACTH secretion in the AtT-20 cell model of the
      rodent corticotrope.

PMID- 12065888
TI  - Biphasic autoregulation of mineralocorticoid receptor mRNA in the medial septal
      nucleus by aldosterone.
AB  - The time-dependent action of aldosterone was analyzed on the regulation of
      mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) mRNAs in the
      brain. Bilaterally adrenalectomized rats were injected subcutaneously with a
      single low dose of aldosterone (0.01 mg/kg, s.c.). By means of in situ
      hybridization MR and GR mRNA levels were studied in autoradiograms 2, 4, 8 and 24
      h after the hormone injection in brain regions related to stress responses, i.e.
      subregions of the dorsal hippocampus (CA1 to CA4 and dentate gyrus), the
      hypothalamic paraventricular nucleus, and the septum. The findings show a
      biphasic regulation of MR mRNA levels in the medial septal nucleus with
      substantial increases after 4 h (79% increase) followed by substantial decreases
      in MR mRNA levels after 24 h (71% decrease), whereas no changes in MR mRNA levels
      were observed in the lateral septal nucleus. A negative autoregulation of
      hippocampal MR mRNA levels was observed only in the CA2 subregion (38% decrease)
      at the 8-hour time interval. Over the same time interval a negative cross
      regulation of GR mRNA by aldosterone was observed in all hippocampal subfields
      (32-57% decrease) except in CA2. No changes in GR mRNA levels were found in the
      hypothalamic paraventricular nucleus. The time-dependent action of corticosterone
      (10 mg/kg, s.c.) was analyzed in the same animal model revealing no changes in MR
      mRNA levels in the medial and lateral septal nuclei. The present findings suggest
      that the medial septal nucleus shows a unique responsiveness to aldosterone in
      the adrenalectomized model in terms of biphasic changes in MR mRNA levels.
      Activated MR in the medial septal nucleus may therefore take part in the
      regulation of septo-hippocampal cholinergic pathways and thus of limbic circuits.

PMID- 12065887
TI  - Interleukin-12 p40 gene expression is induced in lipopolysaccharide-activated
      pituitary glands in vivo.
AB  - Proinflammatory cytokines have several functions including activation of the
      hypothalamo-pituitary-adrenal (HPA) axis and regulation of the immune system. The
      present study focuses on the regulation of interleukin 12 (IL-12) and its
      receptor gene expression in the HPA axis under artificially induced immune
      stress, brought on by administration of lipopolysaccharide (LPS) to Sprague
      Dawley (SD) rats. RT-PCR analyses showed that expression of the IL-12 p40 gene
      was significantly increased and peaked at 2 h in the pituitary gland, but not in
      the hypothalamus. LPS-induced IL-12 p40 gene induction in the pituitary gland was
      suppressed after beta-adrenoceptor agonist pretreatment in vivo. Both IL-12 p40
      gene induction and IL-12 production were also observed when freshly isolated
      pituitary glands from non-treated SD rats were incubated with LPS in vitro.
      Furthermore, CD14, which is known as a LPS receptor, was found to be expressed in
      the pituitary gland. Gel mobility shift assays using nuclear extracts prepared
      from the pituitary glands of rats administered LPS showed induction of NF-kappaB
      and AP-1 DNA-binding activity. These results suggest that LPS stimulates the
      pituitary gland directly in vivo to increase IL-12 p40 gene expression and IL-12
      protein production.

PMID- 12065889
TI  - Differential interactions of urocortin/corticotropin-releasing hormone peptides
      with the blood-brain barrier.
AB  - The two newest members of the urocortin (UCN)/corticotropin-releasing hormone
      (CRH) family of peptides - UCN II and UCN III - bind to the CRH-2 receptor,
      suppress feeding, and are expressed in the periphery as well as the brain. We
      used several sensitive techniques to examine their interactions with the blood
      brain barrier (BBB). Of the four known peptides in this family, each interacts
      with the BBB differently. UCN I barely enters the brain from blood unless its
      latent saturable influx system is activated by leptin or pretreatment with
      glucose. However, neither leptin nor glucose affected the entry of intact UCN II.
      UCN II reached brain paranchyma at a moderate rate that was not self-inhibited or
      cross-inhibited by UCN/CRH peptides. The apparent, but misleading, rapid influx
      of UCN III (stresscopin) could be explained by degradation at the BBB itself.
      Influx of CRH into brain was slower than UCN II but faster than UCN I; it was
      inhibited by excess CRH but not by excess UCN I, II, III, or leptin. CRH is the
      only member of this family to have a saturable efflux system out of the brain.
      Determination of hydrogen bonding, newly applied here to ingestive peptides, was
      not helpful in explaining these differential interactions of the UCN peptides
      with the BBB.

PMID- 12065890
TI  - A role for hypothalamic astrocytes in dehydroepiandrosterone and estradiol
      regulation of gonadotropin-releasing hormone (GnRH) release by GnRH neurons.
AB  - Molecules of astrocyte origin influence gonadotropin-releasing hormone (GnRH)
      release and GnRH neuronal growth and differentiation. Furthermore, type 1
      astrocytes express steroid receptors, presenting the possibility that steroid
      actions on GnRH neurons might occur via astrocytes. Utilizing GT1-7 cells, a GnRH
      secreting cell line, the present study demonstrates that astrocytes mediate
      dehydroepiandrosterone (DHEA) or estradiol (E2) stimulated GnRH secretion.
      Conditioned media (CM) from astrocytes cultured for 48 h alone, with DHEA (DHEA
      CM), or with E2 (E2-CM) were collected, treated with charcoal to remove steroids,
      and added to GT1-7 cells in culture for 12 h to test the effect on GnRH
      secretion. DHEA-CM and E2-CM stimulated GnRH secretion by GT1-7 cells by 4- and 3
      fold, respectively. The effect of DHEA-CM on GnRH secretion by GT1-7 cells
      appears to be related to both DHEA and its metabolite, E2, since blocking the
      metabolism of DHEA into estrogen in the DHEA-treated astrocytes partially
      reversed the stimulatory effect of DHEA-CM. Addition of transforming growth
      factor (TGF)-beta1-neutralizing antibody to the astrocyte cultures reversed the
      stimulatory effects of both DHEA-CM and E2-CM on GnRH secretion by GT1-7 cells,
      suggesting that TGF-beta1 derived from astrocytes may be the principle mediator
      of E2 and DHEA effects. These data provide evidence for a novel mechanism by
      which circulating steroids and/or neurosteroids may modulate GnRH secretion.

PMID- 12065892
TI  - Direct actions of estradiol on the anterior pituitary gland are required for
      hypothalamus-dependent lactotrope proliferation and secretory surges of
      luteinizing hormone but not of prolactin in female rats.
AB  - Estradiol induces surges of prolactin (PRL) and luteinizing hormone (LH)
      secretion as well as lactotrope proliferation in female rats. We examined whether
      these hypothalamus-dependent events require the direct action of estradiol on the
      anterior pituitary gland by selective blockade of its peripheral actions, using
      ICI182,780 (ICI), an antiestrogen that cannot cross the blood-brain barrier.
      Injection of ICI into ovariectomized rats, at a dose of 250 microg/day for 4
      days, almost completely inhibited estradiol-induced growth of the uterus,
      proliferation of lactotropes as determined by bromodeoxyuridine incorporation,
      and afternoon surges of LH secretion. However, ICI only partially inhibited
      estradiol-induced surges of PRL secretion and had no effect on estradiol-induced
      tonic inhibition of LH secretion even at the highest dose of 1,000 microg/day.
      The inhibitory effects of ICI found at 250 microg/day were attributable to its
      selective peripheral, but not central actions since ICI did not alter
      hypothalamic expression of progesterone receptors, an estradiol-dependent brain
      process. Estradiol-induced increases in the number of progesterone receptor
      immunoreactive cells in the hypothalamic ventromedial nucleus and the medial
      preoptic area were not inhibited by this dose of ICI but were inhibited by 500
      microg/day tamoxifen, an antiestrogen that can cross the blood-brain barrier.
      Treatment of cycling female rats with 250 microg/day ICI beginning from diestrus
      day 2 was also effective in blocking estrous lactotrope proliferation and
      preovulatory surges of LH secretion but not PRL secretion. Finally, in
      ovariectomized estradiol-treated pup-deprived lactating rats, ICI did not affect
      suckling-induced PRL secretion but completely blocked lactotrope proliferation.
      These results suggest that a direct estradiol action on the anterior pituitary
      gland is required for lactotrope proliferation and the positive feedback action
      on LH secretion but not for the secretory surges of PRL or for negative feedback.

PMID- 12065891
TI  - Microinjection of dihydrotestosterone into the medial preoptic area produces male
      like pattern of growth hormone secretion in ovariectomized female rats.
AB  - The pattern of growth hormone (GH) secretion is sexually dimorphic in rats. We
      have previously shown that the secretory pattern in adult ovariectomized (OVX)
      female rats is masculinized by the administration of a single dose of
      dihydrotestosterone (DHT), a nonaromatizable androgen. To investigate the primary
      site of action of DHT in the brain, a small amount of DHT was injected directly
      into a defined area of the brain, and the blood GH profile was observed for 18 h
      in conscious adult OVX female rats. The bilateral direct injection of 1 microg
      DHT into the medial preoptic area (MPA) produced a male-like secretory pattern of
      GH in OVX rats. The masculinizing effects became apparent at 9 h after injection,
      from which time the episodic GH secretion was produced regularly at intervals of
      about 150 min, the amplitude of the peak increased and baseline levels were
      lowered. These parameters, analyzed during 9-18 h after DHT injection, were not
      different from those in adult male rats. On the contrary, microinjection of DHT
      into the bed nucleus of the stria terminalis, the hypothalamic periventricular
      nucleus, or the hypothalamic arcuate-ventromedial nucleus did not affect the
      secretory pattern of GH. The data indicate that DHT primarily acts on cells in
      the MPA through androgen receptors and modulates the secretion of somatostatin
      and/or GH-releasing hormone secondarily to masculinize the GH secretory pattern
      in OVX rats.

PMID- 12065893
TI  - The nonstructural NS5A protein of hepatitis C virus: an expanding,
      multifunctional role in enhancing hepatitis C virus pathogenesis.
AB  - The hepatitis C virus (HCV) NS5A gene product is a phosphorylated 56- to 58-kD
      nonstructural protein that displays a multitude of activities related to
      enhancement of viral pathogenesis. Although associated with other viral encoded
      proteins as part of the viral replicase complex positioned on the cytoplasmic
      side of the endoplasmic reticulum, a role for NS5A in viral replication has not
      been defined. Post-translational modifications of NS5A include phosphorylation
      and potential proteolytic processing to smaller molecular weight forms able to
      translocate to the nucleus. Both the identification of a putative interferon
      (IFN) sensitivity-determining region within NS5A, as well as the direct
      interaction with and inhibition of the IFN-induced double-stranded RNA-dependent
      protein kinase (PKR) by NS5A remain controversial. Truncated versions of NS5A can
      act as transcriptional activators, while other recently characterized
      interactions of NS5A with cellular proteins indicate its pleiotropic role in HCV
      host interactions. NS5A itself has no direct effect on IFN-alpha signaling or
      activation, but other abundant interactions with members of the cellular
      signaling apparatus, transcription activation machinery and cell cycle-regulatory
      kinases have been described (e.g. growth factor receptor-bound protein 2, p53,
      p21/waf and cyclins). Many of these interactions block the apoptotic cellular
      response to persistent HCV infection. More recently, another altogether different
      mechanism attenuating the IFN-alpha response was reported based on induction of
      interleukin (IL)-8. IL-8, in model systems, potentiates viral replication and
      mutes the nonspecific intracellular IFN antiviral response. Evidence supporting a
      complex multimechanistic role of NS5A in promoting viral persistence,
      pathogenesis and, indirectly, viral-related hepatocarcinogenesis indicates its
      key role in HCV pathobiology.

PMID- 12065894
TI  - Intracellular pH regulatory mechanism in human atrial myocardium: functional
      evidence for Na(+)/H(+) exchanger and Na(+)/HCO(3)(-) symporter.
AB  - Intracellular pH (pH(i)) exerts considerable influence on cardiac contractility
      and rhythm. Over the last few years, extensive progress has been made in
      understanding the system that controls pH(i) in animal cardiomyocytes. In
      addition to the housekeeping Na(+)-H(+) exchanger (NHE), the Na(+)-HCO(3)(-)
      symporter (NHS) has been demonstrated in animal cardiomyocytes as another acid
      extruder. However, whether the NHE and NHS functions exist in human atrial
      cardiomyocytes remains unclear. We therefore investigated the mechanism of pH(i)
      recovery from intracellular acidosis (induced by NH(4)Cl prepulse) using
      intracellular 2',7'-bis(2-carboxethyl)-5(6)-carboxy-fluorescein fluorescence in
      human atrial myocardium. In HEPES (nominally HCO(3)(-)-free) Tyrode solution,
      pH(i) recovery from induced intracellular acidosis could be blocked completely by
      30 microM 3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride (HOE
      694), a specific NHE inhibitor, or by removing extracellular Na(+). In 3% CO(2)
      HCO(3)(-) Tyrode solution, HOE 694 only slowed the pH(i) recovery, while addition
      of HOE 694 together with 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (an
      NHS inhibitor) or removal of extracellular Na(+) inhibited the acid extrusion
      entirely. Therefore, in the present study, we provided evidence that two acid
      extruders involved in acid extrusion in human atrial myocytes, one which is
      HCO(3)(-) independent and one which is HCO(3)(-) dependent, are mostly likely NHE
      and NHS, respectively. When we checked the percentage of contribution of these
      two carriers to pH(i) recovery following induced acidosis, we found that the
      activity of NHE increased steeply in the acid direction, while that of NHS did
      not change. Our present data indicate for the first time that two acid extruders,
      NHE and NHS, exist functionally and pH(i) dependently in human atrial
      cardiomyocytes.

PMID- 12065895
TI  - Chronic hypoxia attenuates nitric oxide-dependent hemodynamic responses to acute
      hypoxia.
AB  - Alterations in the nitric oxide (NO) pathway have been implicated in the
      pathogenesis of chronic hypoxia-induced pulmonary hypertension. Chronic hypoxia
      can either suppress the NO pathway, causing pulmonary hypertension, or increase
      NO release in order to counteract elevated pulmonary arterial pressure. We
      determined the effect of NO synthase inhibitor on hemodynamic responses to acute
      hypoxia (10% O(2)) in anesthetized rats following chronic exposure to hypobaric
      hypoxia (0.5 atm, air). In rats raised under normoxic conditions, acute hypoxia
      caused profound systemic hypotension and slight pulmonary hypertension without
      altering cardiac output. The total systemic vascular resistance (SVR) decreased
      by 41 +/- 5%, whereas the pulmonary vascular resistance (PVR) increased by 25 +/-
      6% during acute hypoxia. Pretreatment with N(omega)-nitro-L-arginine methyl ester
      (L-NAME; 25 mg/kg) attenuated systemic vasodilatation and enhanced pulmonary
      vasoconstriction. In rats with prior exposure to chronic hypobaric hypoxia, the
      baseline values of mean pulmonary and systemic arterial pressure were
      significantly higher than those in the normoxic group. Chronic hypoxia caused
      right ventricular hypertrophy, as evidenced by a greater weight ratio of the
      right ventricle to the left ventricle and the interventricular septum compared to
      the normoxic group (46 +/- 4 vs. 28 +/- 3%). In rats which were previously
      exposed to chronic hypoxia (half room air for 15 days), acute hypoxia reduced SVR
      by 14 +/- 6% and increased PVR by 17 +/- 4%. Pretreatment with L-NAME further
      inhibited the systemic vasodilatation effect of acute hypoxia, but did not
      enhance pulmonary vasoconstriction. Our results suggest that the release of NO
      counteracts pulmonary vasoconstriction but lowers systemic vasodilatation on
      exposure to acute hypoxia, and these responses are attenuated following
      adaptation to chronic hypoxia.

PMID- 12065896
TI  - Characterization of bradykinin receptors in canine cultured corneal epithelial
      cells: pharmacological and functional studies.
AB  - The pharmacological properties of bradykinin (BK) receptors were characterized in
      canine cultured corneal epithelial cells (CECs) using [(3)H]-BK as a radioligand.
      Analysis of binding isotherms gave an apparent equilibrium dissociation constant
      of 0.34 +/- 0.07 nM and a maximum receptor density of 179 +/- 23 fmol/mg protein.
      Neither a B(1) receptor-selective agonist (des-Arg(9)-BK) nor antagonist
      ([Leu(8), des-Arg(9)]-BK) significantly inhibited [(3)H]-BK binding to CECs, thus
      excluding the presence of B(1) receptors in canine CECs. The specific binding of
      [(3)H]-BK to CECs was inhibited by B(2) receptor-selective agonists (BK and
      kallidin) and antagonists (Hoe 140 and [D-Arg(0), Hyp(3), Thi(5,8), D-Phe(7)]
      BK), with a best fit using a one-binding-site model. The order of potency for the
      inhibition of [(3)H]-BK binding was BK = Hoe 140 > kallidin > [D-Arg(0), Hyp(3),
      Thi(5,8), D-Phe(7)]-BK. Stimulation of CECs by BK produced a concentration
      dependent accumulation of inositol phosphates (IP) and an initial transient peak
      of intracellular Ca(2+). B(2) receptor-selective antagonist ([D-Arg(0), Hyp(3),
      Thi(5,8), D-Phe(7)]-BK) significantly antagonized the BK-induced responses with
      dissociation constants of 6.0-6.1. Pretreatment of CECs with pertussis toxin
      (PTX) or cholera toxin did not alter the BK-induced IP accumulation. Incubation
      of CECs in the absence of external Ca(2+) led to a significant attenuation of the
      IP accumulation induced by BK. These results demonstrate that BK directly
      stimulates phospholipase C-mediated signal transduction through BK B(2) receptors
      via a PTX-insensitive G protein in canine CECs. This effect may function as the
      transducing mechanism for BK-mediated cellular responses.

PMID- 12065897
TI  - The effect of C-terminal mutations of HSP60 on protein folding.
AB  - HSP60 is an essential gene in Saccharomyces cerevisiae. The protein forms
      homotetradecameric double toroid complexes. The flexible C-terminal end of each
      subunit, which is hydrophobic in nature, protrudes inside the central cavity
      where protein folding occurs. In order to study the functional role of the C
      terminus of Hsp60, we generated and characterized yeast strains expressing
      mutants of Hsp60 proteins. Most of the yeast strains expressing Hsp60 with C
      terminal deletions grew normally, unless the deletion impaired the interaction
      between neighboring subunits. The cells carrying Hsp60 mutants with an epitope of
      influenza hemagglutinin (HA) and T7 alone in the C-terminal region grew normally,
      but the mutant containing both HA and T7 was unable to grow in nonfermentable
      carbon sources. In vitro biochemical assays were performed using purified Hsp60
      proteins. All the mutants examined remained capable of interacting with Hsp10 in
      a nucleotide-dependent manner. However, binding and/or refolding of denatured
      rhodanese became defective in most of the hsp60 mutants. Therefore, the
      hydrophobic C-terminal tail of Hsp60 plays an important role in the refolding of
      protein substrates, although it is flexible in structure.

PMID- 12065899
TI  - Natural plasmid transformation in Escherichia coli.
AB  - Although Escherichia coli does not have a natural transformation process, strains
      of E. coli can incorporate extracellular plasmids into cytoplasm 'naturally' at
      low frequencies. A standard method was developed in which stationary phase cells
      were concentrated, mixed with plasmids, and then plated on agar plates with
      nutrients which allowed cells to grow. Transformed cells could then be selected
      by harvesting cells and plating again on selective agar plates. Competence
      developed in the lag phase, but disappeared during exponential growth. As more
      plasmids were added to the cell suspension, the number of transformants
      increased, eventually reaching a plateau. Supercoiled monomeric or linear
      concatemeric DNA could transform cells, while linear monomeric DNA could not.
      Plasmid transformation was not related to conjugation and was recA-independent.
      Most of the E. coli strains surveyed had this process. All tested plasmids,
      except pACYC184, could transform E. coli. Insertion of a DNA fragment containing
      the ampicillin resistance gene into pACYC184 made the plasmid transformable. By
      inserting random 20-base-pair oligonucleotides into pACYC184 and selecting for
      transformable plasmids, a most frequent sequence was identified. This sequence
      resembled the bacterial interspersed medium repetitive sequence of E. coli,
      suggesting the existence of a recognition sequence. We conclude that plasmid
      natural transformation exists in E. coli.

PMID- 12065900
TI  - Analysis of adeno-associated virus-mediated ex vivo transferred human beta-globin
      gene in bone marrow engrafted mice.
AB  - Adeno-associated virus (AAV)-2 was developed as a useful vector for human gene
      therapy. In this report, we analyzed the integration and expression of AAV
      mediated ex vivo transferred human beta-globin gene in bone marrow (BM)
      reconstituted mice. Recombinant AAV (rAAV) containing human beta-globin gene was
      packaged by infecting individual G418-resistant BHK-21 cell clones integrated
      with the plasmid AV53HS432Deltabeta2.0Neo with recombinant herpes simplex virus,
      which can express rep and cap genes of wild-type AAV. The titer of rAAV was
      determined using slot blot hybridization with a result of 10(13) virus
      particles/ml (genome copy number). Low-density mononuclear cells were isolated
      from fetal livers of embryos from pregnant C57BL/6 mice at 14-16 days of
      gestation and were infected with rAAV. The transduced hematopoietic cells were
      then reinfused into lethally irradiated C57BL/6 recipient mice via tail vein
      injection. To analyze the provirus in short-term and long-term BM reconstituted
      mice, PCR/Southern blot and RT-PCR were performed to identify the integrity of
      the provirus and to detect the expression of human beta-globin gene,
      respectively. Genomic DNA was extracted from spleen nodules of BM reconstituted
      mice 12 days after transplantation. Human beta-globin gene was detected in 1 out
      of 6 nodules using PCR combined with Southern blot. Human beta-globin gene was
      also detected in the BM and thymus of mouse Y6161, in the thymus and spleen of
      mouse Y6162 and in the BM of mice Y6211 and Y6212. RT-PCR revealed low levels of
      expression of human beta-globin gene in the BM of mouse Y6211. Our results
      suggested that the efficiency of AAV-mediated human beta-globin gene integration
      into hematopoietic stem/progenitor cells was very low. It is necessary to perform
      further research on AAV biology before applying gene therapy that requires
      integration of a foreign gene into host chromosomes.

PMID- 12065898
TI  - MCEF, the newest member of the AF4 family of transcription factors involved in
      leukemia, is a positive transcription elongation factor-b-associated protein.
AB  - Positive transcription elongation factor-b (P-TEFb) contains CDK9 and cyclin
      T(1). P-TEFb was affinity purified from a stably transfected cell line that
      expresses epitope-tagged CDK9, and proteins that appeared to be specifically
      bound were sequenced. In addition to CDK9, previously identified isoforms of
      cyclin T (including T(1), T(2A) and T(2B)), HSP90 and CDC37, this analysis
      identified a novel protein named MCEF. Cloning of its cognate cDNA revealed that
      MCEF is the newest member of the AF4 family of transcription factors involved in
      acute lymphoblastic leukemia. MCEF RNA was expressed in all human tissues
      examined, and antisera directed against recombinant MCEF specifically
      immunoprecipitated P-TEFb. Ectopic expression of MCEF did not activate HIV-1
      replication, and tethering of MCEF to a promoter did not activate transcription.

PMID- 12065901
TI  - Hepatocyte growth factor upregulates alpha2beta1 integrin in Madin-Darby canine
      kidney cells: implications in tubulogenesis.
AB  - It has been well established that hepatocyte growth factor (HGF) induces
      branching tubule formation of Madin-Darby canine kidney (MDCK) cells cultured in
      collagen gel. Tubulogenesis per se requires the involvement of cell
      proliferation, migration, focalization proteolysis, cell-cell interaction and
      differentiation. However, signaling pathways and proteins involved in HGF-induced
      tubulogenesis by MDCK cells have not been thoroughly studied. Because cell-matrix
      interactions play important roles in tubulogenesis, we analyzed whether HGF
      altered the expression of extracellular matrix receptor (alpha2, alpha3, beta1
      and alphavbeta3 integrin). We found that among those proteins examined,
      alpha2beta1 integrin levels were enhanced by HGF. HGF-induced upregulation of
      alpha2beta1 integrin was mediated via upregulation of alpha2 integrin mRNA
      abundance. Cycloheximide blocked the HGF-induced increase in alpha2 integrin mRNA
      expression. To understand the signaling pathways leading to an HGF-induced
      increase in alpha2beta1 integrin levels, PD98059 (MEK1 inhibitor), LY294002 (PI3
      kinase inhibitor), and GF109203X (PKC inhibitor) were used. We found that PD98059
      blocked the HGF-induced increase in alpha2beta1 integrin expression. Furthermore,
      5E8 (specific anti-alpha2beta1 integrin antibody) was employed to elucidate the
      potential role of HGF-induced upregulation of alpha2beta1 integrin in branching
      morphogenesis. 5E8 did not alter HGF-induced scattering effects but disrupted HGF
      induced branching tubulogenesis in collagen gel via inhibition of cell-cell
      interactions and growth. Taken together, HGF upregulates alpha2beta1 integrin
      expression via an indirect pathway, the results of which contribute to the
      regulation of cell-cell interactions and cell growth during branching
      morphogenesis in collagen gel.

PMID- 12065902
TI  - Stimulation of human flap endonuclease 1 by human immunodeficiency virus type 1
      integrase: possible role for flap endonuclease 1 in 5'-end processing of human
      immunodeficiency virus type 1 integration intermediates.
AB  - Human immunodeficiency virus type 1 (HIV-1) DNA integration intermediates consist
      of viral and host DNA segments separated by a 5-nucleotide gap adjacent to a 5'
      AC unpaired dinucleotide. These short-flap (pre-repair) integration intermediates
      are structurally similar to DNA loci undergoing long-patch base excision repair
      in mammalian cells. The cellular proteins flap endonuclease 1 (FEN-1),
      proliferating cell nuclear antigen, replication factor C, DNA ligase I and DNA
      polymerase delta are required for the repair of this type of DNA lesion. The role
      of FEN-1 in the base excision repair pathway is to cleave 5'-unpaired flaps in
      forked structures so that DNA ligase can seal the single-stranded breaks that
      remain following gap repair. The rate of excision by FEN-1 of 5'-flaps from short
      and long-flap oligonucleotide substrates that mimic pre- and post-repair HIV-1
      integration intermediates, respectively, and the effect of HIV-1 integrase on
      these reactions were examined in the present study. Cleavage of 5'-flaps by FEN-1
      in pre-repair HIV-1 integration intermediates was relatively inefficient and was
      further decreased 3-fold by HIV-1 integrase. The rate of removal of 5'-flaps by
      FEN-1 from post-repair HIV-1 integration intermediates containing relatively long
      (7-nucleotide) unpaired 5'-tails and short (1-nucleotide) gaps was increased 3
      fold relative to that seen with pre-repair substrates and was further stimulated
      5- to 10-fold by HIV-1 integrase. Overall, post-repair structures were cleaved 18
      times more effectively in the presence of HIV-1 integrase than pre-repair
      structures. The site of cleavage was 1 or 2 nucleotides 3' of the branch point
      and was unaffected by HIV-1 integrase. Integrase alone had no detectable activity
      in removing 5'-flaps from either pre- or post-repair substrates.

PMID- 12065903
TI  - Effect of extracellular matrix proteins on platelet-activating factor-induced
      eosinophil chemotaxis.
AB  - BACKGROUND: Eosinophils accumulate in tissues during various allergic
      inflammatory processes. Selective eosinophil recruitment is the result of
      orchestrated events involving cell adhesion molecules and chemoattractants.
      However, the exact mechanism of the regulation of integrin avidity during
      interstitial migration is poorly understood. OBJECTIVE: The purpose of this study
      was to investigate whether extracellular matrix proteins might activate human
      eosinophil chemotaxis and, if so, to clarify the mechanism in terms of integrin
      avidity. METHOD: Eosinophils were purified from the peripheral blood of healthy
      donors. Eosinophil migration was measured using Boyden chambers with filter
      membranes coated with fibronectin (Fn), vitronectin (Vn), laminin (Ln),
      hyaluronic acid, collagen type IV, or bovine serum albumin (BSA) overnight.
      Platelet-activating factor (PAF) was introduced into the lower chamber of each
      well. Eosinophils were placed in the upper chamber after incubation with IL-5 for
      15 min. The number of eosinophils that transmigrated into the lower chamber was
      calculated by measuring the eosinophil peroxidase activity. RESULTS: Fn, Ln and
      BSA enhanced PAF-induced chemotaxis of eosinophils. Inhibition experiments using
      blocking monoclonal antibodies showed that in the early phase of chemotaxis, Fn
      and Ln facilitated eosinophil chemotaxis that was mediated by alpha4 and alpha6
      integrins, respectively. In the late phase of chemotaxis, BSA, but not other
      matrix proteins, facilitated both chemokinesis and chemotaxis that was mediated
      by beta2 integrin. CONCLUSION: Our data strongly suggest that during chemotaxis,
      matrix proteins might activate eosinophils via binding with integrins to
      facilitate PAF-induced chemotaxis, and that such a mechanism might participate in
      allergic inflammatory processes.

PMID- 12065904
TI  - Histamine and serotonin stimulate eotaxin production by a human lung fibroblast
      cell line.
AB  - Histamine and serotonin are important inflammatory mediators in the
      pathophysiology of asthma, and asthmatic patients have higher plasma histamine
      and serotonin levels than nonasthmatic control subjects. Eotaxin, a potent
      eosinophil-specific chemotactic factor, is increased in the lower respiratory
      tract of allergic patients. Recently, lung fibroblasts have been reported to
      produce eotaxin and are suggested to be the major cellular source of eotaxin. We
      postulated that lung fibroblasts might release eotaxin in response to histamine
      or serotonin. To test this hypothesis, we evaluated the potential of histamine or
      serotonin to induce the release of eotaxin by the human fetal lung fibroblast
      cell line, HFL-1. HFL-1 released eotaxin in response to histamine and serotonin
      in a dose- and time-dependent manner (p < 0.05). Histamine or serotonin treatment
      of HFL-1 augmented the expression of eotaxin mRNA. Eosinophil chemotactic
      activity by HFL-1 supernatant fluids was inhibited by anti-human eotaxin
      neutralizing antibody. These findings lead to the hypothesis that lung-fibroblast
      derived eotaxin may in part be responsible for the eosinophil infiltration
      observed in allergic disease of the airways.

PMID- 12065905
TI  - Cross-talk between integrins and chemokines that influences eosinophil adhesion
      and migration.

PMID- 12065906
TI  - Potential initiation of eosinophilic skin inflammation by antigen-specific T
      helper type 2 cells.

PMID- 12065907
TI  - Mucosal immunity: its role in defense and allergy.
AB  - The interface between the organism and the outside world, which is the site of
      exchange of nutrients, export of products and waste components, must be
      selectively permeable and at the same time, it must constitute a barrier equipped
      with local defense mechanisms against environmental threats (e.g. invading
      pathogens). The boundaries with the environment (mucosal and skin surfaces) are
      therefore covered with special epithelial layers which support this barrier
      function. The immune system, associated with mucosal surfaces covering the
      largest area of the body (200-300 m(2)), evolved mechanisms discriminating
      between harmless antigens and commensal microorganisms and dangerous pathogens.
      The innate mucosal immune system, represented by epithelial and other mucosal
      cells and their products, is able to recognize the conserved pathogenic patterns
      on microbes by pattern recognition receptors such as Toll-like receptors, CD14
      and others. As documented in experimental gnotobiotic models, highly protective
      colonization of mucosal surfaces by commensals has an important stimulatory
      effect on postnatal development of immune responses, metabolic processes (e.g.
      nutrition) and other host activities; these local and systemic immune responses
      are later replaced by inhibition, i.e. by induction of mucosal (oral) tolerance.
      Characteristic features of mucosal immunity distinguishing it from systemic
      immunity are: strongly developed mechanisms of innate defense, the existence of
      characteristic populations of unique types of lymphocytes, colonization of the
      mucosal and exocrine glands by cells originating from the mucosal organized
      tissues ('common mucosal system') and preferential induction of inhibition of the
      responses to nondangerous antigens (mucosal tolerance). Many chronic diseases,
      including allergy, may occur as a result of genetically based or environmentally
      induced changes in mechanisms regulating mucosal immunity and tolerance; this
      leads to impaired mucosal barrier function, disturbed exclusion and increased
      penetration of microbial, food or airborne antigens into the circulation and
      consequently to exaggerated and generalized immune responses to mucosally
      occurring antigens, allergens, superantigens and mitogens.

PMID- 12065908
TI  - Cloning, isolation, and IgE-binding properties of Helix aspersa (brown garden
      snail) tropomyosin.
AB  - BACKGROUND: Gastropod consumption is quite frequent in the Mediterranean
      countries and cross-reactivities with crustaceans have been described, but the
      mechanism of this allergenic cross-reactivity has not been studied in detail.
      This study aimed to produce recombinant Helix aspersa (brown garden snail)
      tropomyosin and investigate its implication for cross-reactivity among
      invertebrates. METHODS: A tropomyosin-specific cDNA encoding H. aspersa
      tropomyosin was synthetized, and recombinant allergen was overexpressed in
      Escherichia coli as nonfusion protein. IgE-binding reactivity was studied by
      immunoblotting and immunoblot inhibition experiments with sera from snail
      allergic patients. RESULTS: Cloned brown garden snail tropomyosin shares high
      homology with other edible mollusk tropomyosins (84-69% identity) as well as with
      those from arthropods (65-62%), and less homology with vertebrate ones (56%
      identity). Tropomyosin reacted with 18% of the sera from patients with snail
      allergy. Inhibition experiments, using natural and recombinant tropomyosins,
      showed different degrees of cross-reactivity between invertebrate tropomyosins.
      Sera from snail-allergic subjects recognized tropomyosins in both mollusks and
      crustacean extracts. CONCLUSIONS: Tropomyosin represents a minor allergen in
      snail extracts, but it is clearly involved in invertebrate cross-reactivity.

PMID- 12065909
TI  - Identification and characterisation of the IgE-binding proteins 2S albumin and
      conglutin gamma in almond (Prunus dulcis) seeds.
AB  - BACKGROUND: Almond proteins can cause severe anaphylactic reactions in
      susceptible individuals. The aim of this study was the identification of IgE
      binding proteins in almonds and the characterisation of these proteins by N
      terminal sequencing. METHODS: Five sera were selected from individuals with a
      positive reaction to food challenge. Sodium dodecylsulphate-polyacrylamide gel
      electrophoresis and immunoblotting were performed on almond seed proteins.
      Purified IgE-binding proteins were tested for immunoblot inhibition with sera pre
      incubated with extracts of hazelnut and walnut. RESULTS: N-terminal sequences of
      the 12-, 30- and 45-kD proteins were obtained. The 45- and 30-kD proteins shared
      the same N terminus, with 60% homology to the conglutin gamma heavy chain from
      lupine seed (Lupinus albus) and to basic 7S globulin from soybean (Glycine max).
      The sequences of the N-terminal 12-kD protein and of an internal peptide obtained
      by endoproteinase digestion showed good homology to 2S albumin from English
      walnut (Jug r 1). Immunoblot inhibition experiments were performed and IgE
      binding to almond 2S albumin and conglutin gamma was detected in the presence of
      cross-reacting walnut or hazelnut antigens. CONCLUSIONS: Two IgE-binding almond
      proteins were N-terminally sequenced and identified as almond 2S albumin and
      conglutin gamma. Localisation and conservation of IgE binding in a 6-kD peptide
      obtained by endoproteinase digestion of 2S albumin was shown.

PMID- 12065910
TI  - IgE reactivity to profilin in pollen-sensitized subjects with adverse reactions
      to banana and pineapple.
AB  - BACKGROUND: The so-called 'latex-fruit syndrome' is a well-documented phenomenon
      in cross-reactive allergies. By contrast, there is a lack of information about
      allergy to exotic fruits in patients with a predominant pollen sensitization.
      Since the ubiquitous protein profilin has been identified as an allergen in
      natural rubber latex as well as in pollen-related foods, the aim of this study
      was to investigate the role of profilin in allergy to certain exotic fruits.
      METHODS: Recombinant profilins from banana and pineapple were cloned by a PCR
      technique after isolation of total RNA using degenerated profilin-specific
      primers. The unknown 5' ends of copy DNA (cDNA) were identified by rapid
      amplification of 5'cDNA ends (5'-RACE) and expression in Escherichia coli
      BL21(DE3) cells. The recombinant profilins were purified by affinity
      chromatography using poly-(L)-proline as the solid phase. IgE-binding
      capabilities were characterized by means of immunoblot and Enzyme Allergosorbent
      Test (EAST). The cross-reactivity to birch pollen profilin and latex profilin was
      studied by EAST as well as by immunoblot inhibition experiments. RESULTS: Both
      banana and pineapple profilin were found to consist of 131 amino acid residues
      with high amino acid sequence identity to known allergenic pollen and food
      profilins (71-84%). IgE binding to the recombinant profilins was observed in 7/16
      sera from subjects with suspected banana allergy (44%) and in 8/19 sera from
      subjects with suspected pineapple allergy (42%). Inhibition experiments indicated
      similar IgE reactivity of natural and recombinant allergens. In addition, high
      cross-reactivity to birch pollen profilin Bet v 2 and latex profilin Hev b 8 was
      demonstrated by immunoblot inhibition as well as EAST inhibition experiments.
      CONCLUSIONS: Since a high IgE-binding prevalence of about 40% was obtained in
      both banana and pineapple allergy, we conclude that profilin is an important
      mediator of IgE cross-reactivity between pollen and exotic fruits.

PMID- 12065911
TI  - Patterns of reactivity to lipid transfer proteins of plant foods and Artemisia
      pollen: an in vivo study.
AB  - BACKGROUND: Lipid transfer proteins (LTPs) are major allergens of Rosaceae fruits
      in the Mediterranean area. IgE-cross-reactivity has been demonstrated in vitro
      among LTPs from peach, apple, chestnut and Artemisia pollen. The aim of this
      study was to evaluate the reactivity to LTPs from peach, apple, chestnut and
      Artemisia pollen by means of skin prick tests (SPTs). METHODS: Forty-seven
      patients allergic to peach (peach group), 20 patients sensitized to Artemisia
      pollen with no food allergies (Artemisia group), and 12 control subjects were
      skin tested with fresh peach, as well as with whole extracts and purified LTPs of
      peach, apple, chestnut and Artemisia pollen. RESULTS: The rates of positive SPTs
      for peach, apple, chestnut and Artemisia LTPs were, respectively, 91, 77, 23, and
      36% in the peach group, and 30, 5, 15 and 40% in the Artemisia group. No response
      was observed in the control subjects. SPTs with peach LTP strongly correlated
      with SPTs conducted with fresh peach. In the peach group, the most frequent
      pattern of reactivity to LTPs was the combination peach-apple (45%), followed by
      peach-apple-Artemisia-chestnut (21%). Significant correlations were found between
      peach and apple LTPs, and between Artemisia and chestnut LTPs. Positive SPTs to
      chestnut LTP were only observed in patients with positive SPTs to Artemisia LTP.
      All the patients with positive case histories to chestnut reacted to chestnut
      LTP. CONCLUSIONS: LTPs are plant panallergens with different patterns of cross
      reactivity. They are major allergens of Rosaceae fruits and seem to be involved
      in allergic reactions to unrelated foodstuffs such as chestnut, probably through
      sensitization to the cross-reactive Artemisia LTP. Rosaceae LTPs could be useful
      tools for in vivo diagnosis of Rosaceae fruit allergy.

PMID- 12065912
TI  - Trisetum paniceum (wild oats) pollen counts and aeroallergens in the ambient air
      of Madrid, Spain.
AB  - BACKGROUND: Madrid has a short but intensive grass pollen season, in which 79% of
      the total grass pollen load is released from the middle of May to the middle of
      June. The main objectives of this study were to quantify Trisetum paniceum (wild
      oats) aeroallergen in the atmosphere in Madrid from February to December 1996 and
      to correlate the aeroallergen concentrations with grass pollen counts. METHODS:
      Two different samplers were used to assess allergen exposure; a Burkard spore
      trap was used to collect pollen grains and a high-volume air sampler to collect
      airborne particles. A total of 182 air filters were collected and extracted in 1
      ml of PBS and analysed by ELISA inhibition, using pooled sera from highly
      allergic individuals. RESULTS: T. paniceum aeroallergens were detected not only
      during the grass pollen season, but also before and after. Wild oat allergens had
      two main peaks of 1 and 1.9 microg/m(3), occurring in late May and July,
      respectively. The time series analysis established the existence of lags between
      the two main variables pollen counts and aeroallergen activity. Analysis of the
      data by the Spearman rank test and linear regression showed a weak correlation
      between grass allergenic activity and grass pollen counts (Spearman's rho =
      0.29). Data obtained from time series analysis demonstrated that grass allergenic
      activity correlated strongly with current and 5-week-old grass pollen grain
      counts (r(2) = 0.73). CONCLUSIONS: Wild oats allergenic activity was detected
      during the entire year and not only during the pollen season. This fact is an
      important aspect to be considered in the clinical follow-up and treatment of
      grass pollen-sensitised patients in Madrid.

PMID- 12065913
TI  - Theophylline inhibits NF-kappaB activation in human peripheral blood mononuclear
      cells.
AB  - BACKGROUND: Theophylline not only dilates the bronchi, but also modulates the
      production of proinflammatory cytokines and inhibits inflammation. Theophylline
      exerts an antiinflammatory effect on allergic inflammation through inhibition of
      NF-kappaB activation in mast cells. However, the action of theophylline on
      monocytes/macrophages and T cells is unknown. METHODS: We examined whether or not
      theophylline inhibits tumor necrosis factor (TNF)-alpha-induced activation of the
      nuclear transcription factor NF-kappaB, a factor that is essential for the
      expression of proinflammatory cytokines, in human monocytic U-937 cells, a T cell
      line (Jurkat) and peripheral blood mononuclear cells (PBMC). The inhibitory
      effect of theophylline on TNF-alpha-induced NF-kappaB activation was evaluated by
      Western blotting, flow cytometry and chloramphenicol acetyltransferase (CAT)
      assaying. Expression of the IkappaBalpha protein was evaluated by Western
      blotting. RESULTS: Western blotting demonstrated that theophylline inhibits NF
      kappaB activation in U-937 and Jurkat cells and PBMC. Flow cytometry demonstrated
      that theophylline inhibits NF-kappaB activation in U-937 and Jurkat cells in a
      dose-related manner. CAT assaying indicated that NF-kappaB-dependent reporter
      gene expression is inhibited in U-937 cells pretreated with theophylline. Western
      blotting of cytoplasmic extracts of U-937 cells revealed that this inhibition was
      linked to theophylline-induced preservation of expression of the IkappaBalpha
      protein. CONCLUSIONS: These findings are consistent with the idea that
      theophylline suppresses the production of proinflammatory cytokines via
      inhibition of NF-kappaB activation through preservation of the IkappaBalpha
      protein in monocytes/macrophages and T cells.

PMID- 12065914
TI  - Serum tryptase levels in patients with mastocytosis: correlation with mast cell
      burden and implication for defining the category of disease.
AB  - BACKGROUND: The serum tryptase level is used as a diagnostic marker in
      mastocytosis and is considered to reflect the burden of (neoplastic) mast cells
      (MC). METHODS: In the present study, serum tryptase levels were measured in
      patients with mastocytosis by fluoroenzyme immunoassay and compared with the
      extent of infiltration of the bone marrow (BM) by neoplastic MC, determined by
      tryptase immunohistochemistry. Sixteen patients with cutaneous mastocytosis (CM)
      and 43 patients with systemic mastocytosis (SM) were examined. RESULTS: In most
      patients with CM (defined by the absence of dense compact MC infiltrates in
      tryptase-stained BM sections), normal or near-normal serum tryptase levels
      (median 10 ng/ml, range 2-23 ng/ml) were measured. By contrast, in the vast
      majority of patients with SM, elevated serum tryptase levels (median 67 ng/ml)
      were found. In addition, there was a significant correlation between the grade of
      infiltration of the BM by neoplastic MC and tryptase levels in patients with SM
      (r = 0.8). Moreover, enzyme levels differed significantly among the groups of
      patients with different types of SM. The highest levels (>900 ng/ml) were
      detected in the patient with MC leukemia, 2 patients with slowly progressing SM
      and high MC burden (smoldering SM) and 1 patient with indolent SM. In contrast,
      in all 3 patients with isolated BM mastocytosis (no skin lesions and no signs of
      multiorgan involvement), serum tryptase levels were <20 ng/ml. CONCLUSIONS: In
      summary, our data suggest that the measurement of serum tryptase is a reliable
      noninvasive diagnostic approach to estimate the burden of MC in patients with
      mastocytosis and to distinguish between categories of disease.

PMID- 12065915
TI  - Expression of the interleukin-8 receptors CXCR1 and CXCR2 on cord-blood-derived
      cultured human mast cells.
AB  - BACKGROUND: An increase in mast cell number at sites of inflamed tissues has been
      observed. However, the expression of CXC chemokine receptors on human mast cells
      is poorly understood. METHODS: Cultured human mast cells were raised from human
      umbilical cord blood cells in the presence of stem cell factor and interleukin-6
      (IL-6). The expression of surface chemokine receptors on the mast cells was
      analyzed by flow cytometry and that of mRNA was examined by the method of reverse
      transcriptase-polymerase chain reaction (RT-PCR). As functional assays for the
      receptors, mast cell migration was examined by a microchemotaxis assay and
      changes in the cytosolic free intracellular calcium concentrations ([Ca2+]i) was
      measured using fura-2-loaded mast cells, respectively. RESULTS: Expression of IL
      8 receptors CXCR1 and CXCR2 was demonstrated by flow cytometry and of both mRNA
      by RT-PCR; however, CC chemokine receptors including CCR3 were not expressed on
      cord-blood-derived cultured human mast cells. IL-8 and its homologues showed
      chemotactic activity toward them in a dose-dependent manner, and IL-8 induced a
      dose-dependent rapid and transient increase in [Ca2+]i in the mast cells.
      CONCLUSIONS: Our results suggest the surface expression of functional CXCR1 and
      CXCR2 on cord-blood-derived cultured human mast cells.

PMID- 12065916
TI  - Epinephrine fails to hasten hemodynamic recovery in fully developed canine
      anaphylactic shock.
AB  - BACKGROUND: Epinephrine (Epi) is the treatment of choice for reversing
      cardiovascular collapse in anaphylactic shock (AS). However, there are few data
      supporting its use in this condition, and most treatment guidelines have been
      anecdotally derived. In the present study, the time course of hemodynamic
      recovery from maximal hypotension was investigated in a canine model of AS in
      which Epi was administered by the intravenous (IV), subcutaneous (SQ) and
      intramuscular (IM) routes on different occasions. The findings obtained with Epi
      treatment were compared to those in a nontreatment study. METHODS: Ragweed
      sensitized dogs were examined in respective studies approximately 5 weeks apart
      in which Epi was administered by one of the above routes in a randomized design.
      Either Epi (0.01 mg/kg) or placebo was administered at maximal hypotension, and
      hemodynamics were followed for 3 h after shock. The animals were studied while
      ventilated and anesthetized. Mean arterial pressure (MAP), cardiac output, stroke
      volume (SV), pulmonary wedge pressure (Pwp) and plasma Epi concentrations were
      obtained at each measurement interval. RESULTS: In the IV study, Epi produced a
      transient immediate increase in MAP, SV and Pwp as compared to the nontreatment
      study (144 vs. 52 mm Hg; 32 vs. 12 ml; 9 vs. 5 mm Hg; p < 0.01), but no
      differences were observed 15 min after shock. Hemodynamics were not different
      between Epi and no treatment at any intervals when Epi was given by the SQ and IM
      routes. AS compared with the placebo study, plasma Epi concentrations were higher
      in the IV and IM studies, but not in the SQ study. CONCLUSIONS: Although higher
      Epi concentrations were observed in the IM and IV studies, a sustained benefit in
      hemodynamic recovery was not observed in this anesthetized, ventilated canine
      model. In AS, when administered during maximum shock after mediators have already
      been released, a single IM, IV or SQ dose of Epi may have limited utility in the
      treatment of cardiovascular collapse. Earlier administration of Epi, before
      maximal hypotension occurs, may produce a more beneficial effect.

PMID- 12065917
TI  - Prevalence of Japanese cedar pollinosis among schoolchildren in Japan.
AB  - BACKGROUND: Japanese cedar pollinosis is an important allergic
      rhinoconjunctivitis in Japan in spring. We investigated the relationship between
      the amount of pollen in the air and the prevalence of the disease and
      sensitization to Japanese cedar pollen in this ecological study. METHODS: The IgE
      antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and
      rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every
      year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE
      >or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer
      in March or April. RESULTS: Prevalence rates of Japanese cedar pollinosis were
      13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and
      those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were
      significantly related to the amount of pollen in the air. The proportion of
      subjects with rhinoconjunctival symptoms was relatively constant in each stratum
      of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml). CONCLUSION: High
      exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE
      antibody and a high prevalence of Japanese cedar pollinosis. The relationship
      between the level of JCP-IgE and the proportion of subjects with symptoms was
      relatively constant.

PMID- 12065918
TI  - Enhancement of IgE production in B cells by neutrophils via galectin-3 in IgE
      associated atopic eczema/dermatitis syndrome.
AB  - Spontaneous IgE production by B cells from patients with IgE-associated atopic
      eczema/dermatitis syndrome (AEDS) is enhanced by polymorphonuclear leukocytes
      (PMN) from patients with AEDS, but not by PMN from non-atopic controls. The
      enhancement is abolished by preincubation of PMN with lactose, but not with
      glucose. Anti-galectin-3 serum, but not control rabbit serum, blocked the
      enhancement. These results indicate that AEDS PMN can enhance IgE production via
      galectin-3.

PMID- 12065919
TI  - Proceeding of the 5th Serono Symposia Workshop on Clinical Paediatric
      Endocrinology. Dresden, Germany. September 2-3, 2001.

PMID- 12065920
TI  - The neuroendocrinology of human puberty revisited.
AB  - The fundamental aspects of the hypothalamic luteinizing hormone-releasing hormone
      (LHRH)(1) [1]pulse generator-pituitary gonadotrophin-gonadal apparatus in mammals
      have striking commonalities. There are, however, critical, substantive
      differences in the neuroendocrinology of puberty among species. The onset of
      puberty in the human is marked by an increase in the amplitude of LH pulses, an
      indirect indicator of the increase in amplitude of LHRH pulses. The hypothalamic
      LHRH-pituitary gonadotrophin complex is functional by at least 0.3 gestation in
      the human foetus; the sex difference in the fetal and neonatal pattern of LH and
      FSH secretion is an apparent consequence of imprinting of the fetal hypothalamus
      pituitary-gonadotropin apparatus by fetal testosterone. Until about 6 months of
      age in boys and 12-24 months in girls, the testes and ovaries respond to the
      increased LH in boys and follicle-stimulating hormone (FSH) in girls by secreting
      testosterone and oestradiol, respectively, reaching levels that are not again
      achieved before the onset of puberty. Striking features of the ontogeny of the
      human hypothalamic pulse generator are: (1) its development and function in the
      foetus; (2) the continued function of the hypothalamic LHRH pulse generator
      pituitary gonadotrophin-gonadal axis in infancy; (3) the gradual damping of
      hypothalamic LHRH oscillator activity during late infancy; (4) its quiescence
      during childhood - the so-called juvenile pause; (5) during late childhood the
      gradual disinhibition and reactivation of the LHRH pulse generator, mainly at
      night; (6) the increasing amplitude of the LHRH pulses, which are reflected in
      the progressively increased and changing pattern of circulating LH pulses, with
      the approach of and during puberty. The intrinsic central nervous system (CNS)
      mechanisms responsible for the inhibition of the LHRH pulse generator during
      childhood (the juvenile phase) involve the major role of an inhibitory neuronal
      system - the CNS inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and
      GABAergic neurons, as revealed by studies in the rhesus monkey by Terasawa and
      her associates. With the onset of puberty, the disinhibition and reactivation of
      the LHRH pulse generator is associated with a fall in GABAergic neurotransmission
      and a concomitant increase in the input of excitatory amino acid
      neurotransmitters (including glutamate) and possibly astroglial-derived growth
      factors. Despite remarkable progress over the past three decades, large gaps
      remain in our understanding of the neurobiological, genetic and environmental
      mechanisms involved in the control of the onset of puberty. The role of leptin in
      the control of the onset of puberty is reviewed. Severe leptin deficiency is
      associated with hypogonadotrophic hypogonadism; it appears that a critical level
      of leptin and a leptin signal is required to achieve puberty. The weight of
      evidence supports the hypothesis that leptin acts as one of several permissive
      factors and not a trigger in the onset of human puberty. The application of these
      advances provides a framework for the described classification of sexual
      precocity and delayed puberty.1 GnRH is synonymous with LHRH.

PMID- 12065921
TI  - Factors affecting onset of puberty.
AB  - In humans, foetal and early postnatal growth failure may have persistent
      consequences for growth and pubertal development in later life. During this
      period, the developing organs are still plastic to change their function, which
      may have long-lasting effects. At the time of onset of puberty, acute factors may
      also interfere with pubertal development. Malnutrition, as seen in anorexic
      patients, and chronic diseases with malabsorption or diseases with systemic
      effects result in a delayed onset of puberty. We have observed an earlier onset
      of puberty in girls with low birth weight; menarcheal age also tended to be
      earlier. In boys, a low birth weight tended to be associated with a later
      development. Two rat models with growth failure based on perinatal malnutrition
      have been examined, one with intrauterine growth retardation (IUGR) by ligation
      of the uterine arteries and one with postnatal food restriction (FR) by
      increasing the litter size postnatally. In both models, the rats had a persistent
      postnatal growth failure. The onset of puberty in female rats, defined by vaginal
      opening, was delayed only in the IUGR group. Despite a significantly lower
      weight, there was no difference in the timing of puberty onset in the FR group.
      In IUGR rats, the ovaries had fewer follicles, while FR rats had a normal number
      of follicles but an abnormal maturation pattern. In male rats, both models showed
      a delayed onset of puberty, defined by the balano-preputial separation, as well
      as impaired testicular function, shown by decreased testosterone levels. These
      data indicate that early malnutrition during a critical developmental time window
      may have long-lasting effects on pubertal development, including gonadal
      maturation in both humans and rats.

PMID- 12065922
TI  - Secular trends in pubertal development.
AB  - OBJECTIVE: To describe the secular trend in pubertal development in relation to
      the secular trend in height. METHODS: Literature review of cross-sectional,
      longitudinal and twin studies. RESULTS: Globally, there is a secular trend in
      adolescent growth for an increased mean final height at adulthood. To a lesser
      extent, there is also a secular trend towards earlier puberty. However, it seems
      that the two trends are not strongly connected. The increase in average height
      over the generations can, to a large extent, be explained by an earlier onset of
      the growth hormone-dependent phase of growth in early life. The age when this
      growth 'spurt' occurs in childhood strongly correlates with final height, but is
      not related to the age at peak height velocity during puberty. There is a large
      variation in the timing of the onset of puberty; it is largely influenced
      genetically, as implied by studies in twins. The single environmental factor that
      stands out as most significant - possibly explaining as much as 25% of the
      variation in the timing of puberty - is simply nutritional status in childhood;
      overnutrition and obesity seem to trigger pubertal onset. However, recent studies
      have identified that both shortness and thinness at birth are also associated
      with earlier pubertal maturation - a reverse of their impact during childhood
      years. CONCLUSIONS: More longitudinal studies are needed to understand the short-
      and long-term consequences of secular changes in both final height and pubertal
      development before we know how important the trends are.

PMID- 12065923
TI  - Pathogenesis of precocious puberty in hypothalamic hamartoma.
AB  - Astroglial-derived factors, as transforming growth factor (TGF)alpha and TGFbeta,
      act in the hypothalamus to activate luteinizing hormone-releasing hormone (LHRH)
      secretion. Hypothalamic hamartomas (HHs) contain normal nervous tissue in a
      heterotopic location. When symptomatic, they cause precocious puberty and/or
      characteristic gelastic seizures. Thus far, the pathogenesis of these alterations
      remains unknown. By examining two HHs associated with sexual precocity, we found
      that they contained astroglial cells expressing TGFalpha, but no LHRH neurons. In
      a third patient with HH, only epilepsy was present, but precocious puberty
      developed shortly after surgery, probably as a consequence of a surgery-induced
      lesion. These results imply that some HHs induce sexual precocity by activating
      endogenous LHRH secretion via astroglial-derived factors.

PMID- 12065924
TI  - LH and FSH receptor mutations and their effects on puberty.
AB  - Several mutations have been detected in the genes encoding the gonadotrophin
      receptors, and their phenotypic effects are observed in sexual differentiation,
      pubertal development and fertility of the affected individuals. Both activating
      and inactivating mutations are known for the gonadotrophin receptors. These
      mutations are rare, but they are very elucidating with respect to the details of
      gonadotrophin action, as well as clarifying the molecular pathogenesis of certain
      disorders in the development of reproductive functions. Proper diagnosis of these
      conditions by molecular biological techniques makes it possible to offer specific
      treatment for patients and proper counselling for patients and their families.

PMID- 12065925
TI  - Puberty in children with cancer.
AB  - Cancer may impinge on puberty either directly through a mass lesion effect on the
      reproductive axis or indirectly through hormones secreted by tumours, for example
      human chorionic gonadotrophin, or weight loss, or the actual presence of a
      chronic disease process per se. The more frequent pubertal problems faced by
      children with cancer are due to the impact of treatment either on the central
      nervous system, the hypothalamic-pituitary axis or the gonad; in this review, we
      concentrate on these complications and their potential management.

PMID- 12065926
TI  - Endocrine disrupters and testicular dysgenesis syndrome.
AB  - Over the last couple of generations, we have been exposed to an increasing number
      of endocrine disrupters in our environment, including
      dichlorodiphenyltrichloroethane (DDT), PCB, certain pesticides, the phthalate
      DBP, synthetic steroids in meat and many other agents (table 1), which act as
      agonists or antagonists of sex steroids. Although biologists working with
      wildlife have been concerned about the possible effects of these chemical agents
      on animal reproduction, it appears that clinicians have been less concerned about
      possible health effects in humans. However, the increasing incidence of hormone
      dependent cancers, including cancer of the breast, prostate and testis, and signs
      of an increasing incidence of male reproductive health problems should alert us
      to the possible association between exposure to endocrine disrupters and the
      current high frequency of reproductive problems. In Denmark, for example, 5% of
      all children are now born after assisted reproduction (intracytoplasmic sperm
      injection, in vitro fertilization, donor insemination and intrauterine
      insemination) and 1% of all (mostly young) men develop testicular cancer.
      Evidence exists to support the concept that hypospadias, undescended testis, poor
      semen quality and testicular cancer are symptoms of an underlying testicular
      dysgenesis syndrome, which may be becoming increasingly common due to adverse
      environmental effects. Experimental and epidemiological evidence suggests that
      testicular dysgenesis syndrome is a result of disruption of foetal programming
      and gonadal development during foetal life.

PMID- 12065927
TI  - Novel treatment of delayed male puberty with aromatase inhibitors.
AB  - BACKGROUND: As the evidence for the role of oestrogens in epiphyseal closure
      appears unequivocal, we hypothesized that boys with constitutional delay of
      puberty would attain greater adult height if oestrogen action was suppressed.
      METHODS: We conducted a randomized, double-blind, placebo-controlled study in
      which we treated boys with constitutional delay of puberty with testosterone plus
      placebo or testosterone plus a potent fourth-generation aromatase inhibitor,
      letrozole. FINDINGS: Letrozole effectively inhibited oestrogen synthesis. The
      17beta-oestradiol concentrations increased in the untreated group and in the
      testosterone/placebo-treated group, but in the testosterone/letrozole-treated
      group no such increase was observed until letrozole treatment was discontinued.
      Testosterone concentrations were threefold higher in the testosterone/letrozole
      treated group than in the other groups. Within 18 months, bone age had advanced
      by 1.1 +/- 0.3 years in the untreated group and by 1.7 +/- 0.3 years in the
      testosterone/placebo-treated group, but only by 0.9 +/- 0.2 years in the
      testosterone/letrozole-treated group (p = 0.02 between treatment groups).
      Predicted adult height did not change significantly in the untreated group and in
      the testosterone/placebo-treated group, whereas in the testosterone/letrozole
      treated group the increase was 5.1 +/- 1.2 cm (p = 0.004). CONCLUSIONS: Our
      findings suggest that, if oestrogen action is inhibited in growing adolescents,
      adult height will increase. This observation provides a rationale for studies
      aimed at delaying bone maturation in several growth disorders.

PMID- 12065928
TI  - Puberty in chronically diseased patients.
AB  - Delayed onset of puberty and a reduced pubertal growth spurt are often reported
      in patients suffering from chronic diseases. The basis of abnormal puberty in
      these patients is multifactorial. Nutritional deficiency may contribute to growth
      disorders and delayed puberty. Insufficient food supply and/or eating disorders
      and/or malabsorption of nutrients can be observed in these patients. Moreover,
      increased energy supplies are often needed in patients with chronic lung disease,
      infection or inflammation. More specific factors due to the disease itself may be
      involved in growth and puberty disorders. Abnormalities of the growth hormone
      (GH)-insulin-like growth factor (IGF)1 axis and gonadotrophin secretion have been
      described in patients with chronic renal failure, cystic fibrosis and Crohn's
      disease. More recently, it has been shown that cytokines produced during chronic
      diseases such as juvenile idiopathic arthritis may affect the GH-IGF1 axis.
      Finally, concomitant medication, namely corticosteroids, which are often given to
      these patients, may contribute to delayed puberty and poor pubertal growth.

PMID- 12065929
TI  - Anorexia nervosa: hypogonadotrophic hypogonadism and bone mineral density.
AB  - Anorexia nervosa is a chronic illness that involves a reduction in caloric
      intake, loss of weight and amenorrhoea, either primary or secondary. In addition
      to prolonged amenorrhoea, osteopenia and osteoporosis are the most frequent
      complications. Patients exhibit an alteration in the hypothalamic-pituitary
      gonadal axis, which is responsible for the menstrual disorders. The increase in
      gonadotrophin secretion that can be observed after ponderal recuperation suggests
      that malnutrition could be the most important mechanism involved in the decrease
      in gonadotrophin secretion. The loss of fat tissue, as a consequence of the
      restriction of nutrients, has been associated with hypoleptinaemia, abnormal
      secretion of peptides implicated in food control (neuropeptide Y, melanocortins
      and corticotrophin-releasing hormone, among others) and diminution of the amount
      of total body fat. Despite oestrogen therapy, the severe loss of bone mass may
      progress. Other factors such as weight loss, duration of amenorrhoea and low
      insulin-like growth factor-I (IGF-I) levels could contribute to the loss of bone
      mass in women with anorexia nervosa. The recuperation of weight and, in
      particular, the amount of total body fat could lead to the spontaneous
      recuperation of menstruation.

PMID- 12065930
TI  - Mechanisms of abnormal puberty in coeliac disease.
AB  - Coeliac disease (CD) is one of the most frequent chronic diseases in childhood.
      The clinical spectrum has changed; in addition to the classical gastrointestinal
      form, other clinical manifestations have been described, such as hypogonadism and
      the consequent delay in onset of puberty. Recent studies reported not only a
      significantly retarded menarche in untreated CD girls as compared with girls
      following a gluten-free diet, but also in treated CD a negative effect on
      pregnancy, resulting in lower birth weight and shorter duration of pregnancy. In
      boys, there is a reduced serum level of dihydrotestosterone and an increased
      serum level of luteinizing hormone, an abnormality pattern suggesting androgen
      resistance. The pathogenesis of CD-related reproductive disorders is still
      unclear. Some hypotheses may be tried; for example, in CD there is a high level
      of autoantibodies directed against self-antigens, so there could be antibodies
      directed against hormones or organs critical for pubertal development. Moreover,
      in CD there could be a selective malabsorption of micronutrients essential for
      the metabolism of carrier or receptor proteins for sex hormones.

PMID- 12065931
TI  - Growth prediction models, concept and use.
AB  - There is a principal and qualitative difference between using regression results
      on data from groups of children, and using validated prediction models for
      individual children. Using accurate models, it is now possible to predict the
      growth response to growth hormone (GH) treatment in a slowly growing child with
      GH deficiency (GHD) or in a child with idiopathic short stature (ISS). The growth
      response to the standard dose of GH can be regarded as a bioassay for GH (i.e.
      the tissue GH responsiveness) and the information on this growth response can be
      used for different purposes: to decide about treatment or not, for monitoring,
      and for adjusting the GH dose in order to reach a defined goal for height. This
      last concept is now used in an ongoing prospective randomized GH dose-finding
      trial.

PMID- 12065932
TI  - IMAGe association: additional clinical features and evidence for recessive
      autosomal inheritance.
AB  - Congenital adrenal hypoplasia (CAH) normally occurs in the neonatal period, with
      patients presenting with more or less severe salt-wasting syndrome. X-linked CAH
      has been associated with mutations in the DAX-1 gene, and boys have also been
      shown to have hypogonadotrophic hypogonadism. Recently, in three unrelated boys,
      CAH was associated with intrauterine growth retardation (IUGR), metaphyseal
      dysplasia and genital abnormalities, defining a new association called IMAGe. We
      now report four additional patients with this association, including the first
      living female. The four patients belong to two unrelated families (one brother
      and one sister from each family). These patients have the main clinical
      characteristics of IMAGe association: IUGR, facial dysmorphy (frontal bossing,
      broad nasal bridge, low-set ears), short limbs due to metaphyseal dysplasia, and
      adrenal insufficiency. As these patients are older than the initial three
      patients, we can also describe additional features: short adult height, normal
      puberty in boys as well as in the living girl. The boys have hypospadias
      associated with micropenis. The living girl came to clinical attention at the age
      of 5 years as a result of a familial survey, and careful questioning revealed
      that she had been suffering from mild adrenal insufficiency since early
      childhood. At least one boy has congenital hypotonia due to muscular dystrophy.
      In conclusion, these four new cases display familial transmission, strongly
      suggesting Mendelian autosomal recessive inheritance. Adrenal insufficiency may
      be mild. Hypotonia, described in all the patients, might be related to
      paucisymptomatic muscular dystrophy, as this condition is clearly heterogeneous
      varying with regard to severity, associated manifestations and outcome. If this
      symptom is part of the syndrome, which we cannot assume, it could help to
      localize the candidate gene.

PMID- 12065933
TI  - Fibrous dysplasia.
AB  - DEFINITION: Fibrous dysplasia (FD) of bone is a non-inheritable congenital
      disorder affecting both genders. It is characterized by expanding fibrous
      lesions, which contain bone-forming mesenchymal cells. PATHOPHYSIOLOGY: FD is
      caused by a somatic activating mutation of the alpha subunit of the Gs protein
      (Gsalpha). Bone mesenchymal cells produce a matrix of randomly distributed
      collagen fibres and islands of woven bone. Osteoclasts are responsible for the
      spread of the lesions. CLINICAL FINDINGS: The symptoms are bone pain, fracture,
      bone deformities and neurological deficits. Spontaneous regression of lesions
      does not occur. TREATMENT: Recently, an observational study of treatment with
      bisphosphonate has yielded promising results. There was a decreased intensity of
      bone pain, a decrease in biochemical markers of bone turnover and a
      radiographically apparent 'refilling of osteolytic sites' in about half of the
      patients. CONCLUSIONS: Very little is known about the effects of bisphosphonate
      treatment in children and adolescents with FD. Most patients report decreased
      bone pain after the first pamidronate infusion, which, in our view, justifies the
      use of this drug in severely affected patients. The many unanswered questions
      regarding this form of treatment can only be addressed when a large number of
      patients is treated in a standardized fashion, and data on the outcome are
      collected.

PMID- 12065935
TI  - Amplitude of pubertal growth in short stature children with intrauterine growth
      retardation.
AB  - OBJECTIVE: Pubertal growth contributes to 15-18% of adult height. A blunted
      pubertal peak could contribute to short adult height in short children born with
      intrauterine growth retardation (IUGR). DESIGN AND METHODS: Pubertal growth, from
      onset of puberty to final height, was investigated in 75 short IUGR children: 47
      were treated with recombinant human growth hormone (GH) (tx) before pubertal
      onset (mean dose: 0.4 IU/kg/week); 28 were not treated (no-tx). They were
      compared with 98 normal children. RESULTS: Puberty occurred later in IUGR
      children than in controls (boys 14.2 +/- 1 years vs. 12.1 +/- 0.8 years; girls 12
      +/- 1 years vs. 11.2 +/- 0.8 years; p < 0.0001). In girls, total pubertal growth
      was similar in all three groups (tx: 19.3 +/- 4.8 cm; no-tx 19.8 +/- 4.9 cm;
      controls 20.2 +/- 3.9 cm; non-significant). IUGR boys had a reduced pubertal
      growth (tx: 21.3 +/- 6.2 cm; no-tx: 23.9 +/- 6.1; controls 26.9 +/- 3.9 cm; p <
      0.05). The age at puberty onset was the major determinant of pubertal growth
      amplitude (boys: r = 0.53, p < 0.001; girls: r = 0.45, p < 0.001). IUGR children
      exhibited little catch-up growth during puberty. CONCLUSIONS: In the present
      study, we describe a delayed onset of puberty in short children born with IUGR.
      Moreover, prepubertal GH treatment was associated in boys with a decrease in the
      amplitude of the pubertal spurt, a finding that should be further evaluated in
      clinical trials.

PMID- 12065934
TI  - Growth problems in children with asthma.
AB  - Growth problems are often seen in children with asthma. Rarely, these problems
      may be caused by poor asthma control. Negatively-deviating growth curves in
      asthmatic boys aged 8-15 years are often associated with a chronic delay in
      growth and puberty. Daily treatment with any dose of systemic corticosteroids
      suppresses the growth rate for as long as the treatment is maintained. The risk
      of growth rate suppression due to inhaled corticosteroids depends on the dose,
      administration regimen and delivery device. The risk becomes significant with >
      or =800 microg budesonide from a metered-dose inhaler with a spacer, and with >
      or =400 microg budesonide or fluticasone propionate from a dry-powder inhaler.
      Regardless of the treatment modality applied, all children with asthma should
      have their height growth measured at least every 6 months, and indications for
      endocrine work-up should follow general criteria for a growth-insufficient child.

PMID- 12065936
TI  - Congenital adrenal hyperplasia: lessons from a multinational study.
AB  - A study group of paediatric endocrinologists was established in Austria, Czech
      Republic, Hungary, Slovenia and Slovakia in order to investigate various aspects
      in children with congenital adrenal hyperplasia (CAH). Five hundred and ninety
      eight patients with CAH who were diagnosed between 1969 and 1998 were included in
      order to analyze the following questions. Epidemiological data: There were
      significantly fewer males (43%) than females (57%), and the percentage of males
      did not increase during the observation period. Salt wasters (SW) totalled 64.7%,
      whereas 35.3% had simple virilizing (SV) CAH. Diagnosis was established
      significantly later in boys than in girls (median of 26 vs. 13 days for SW, p <
      0.0001; 1,817 vs. 1,010 days for SV, p < 0.03). Mortality in the general
      population was significantly lower than in CAH siblings (1.8% vs. 7.0%, p <
      0.0001) or in SW children (2.2% vs. 11.3%, p < 0.0001). According to our
      calculation with the present clinical diagnostic criteria in Central Europe, from
      40 expected CAH patients/year, 2-2.5 SW, and one female and four male SV patients
      will not be diagnosed. Auxological data: Growth data from 341 patients were
      analyzed retrospectively. Percentiles were constructed in a longitudinal/cross
      sectional study and pubertal growth was described in a longitudinal analysis.
      Growth of SW patients was impaired in early childhood (0-3 years), but followed a
      normal course until puberty. In contrast, SV children had a normal growth pattern
      during early childhood, but were above the standard thereafter. The pubertal
      growth spurt was of normal magnitude in boys and girls, but started too early.
      Final height was reduced compared with both standard and target heights. There
      was no correlation between final height and age of starting treatment or the year
      of birth. Bone age was accelerated in both CAH types, but more so in SV patients.
      Molecular genetics: Three hundred and fifty-six patients were investigated for 11
      14 of the most frequent mutations by direct allele-specific polymerase chain
      reaction (PCR) and/or PCR followed by sequence-specific oligonucleotide, single
      strand chain polymorphism and restriction fragment length polymorphism. In the
      group as a whole, we most frequently found the Intron 2 splice mutation (30.8%)
      or a deletion/conversion (28.5%). The Intron 2 mutation was most frequent in the
      Hungarian population, whereas deletions/conversions were found more frequently in
      Slovenians. The other mutations had a similar distribution to those seen in other
      populations. Genotype-phenotype correlation confirms previous reports.

PMID- 12065937
TI  - The social organisation of a population of Sumatran orang-utans.
AB  - Female orang-utans in a Sumatran swamp forest live in large, but stable, and
      widely overlapping home ranges. They preferentially associate with some of their
      female neighbours, possibly relatives, to form socially distinct clusters that
      also experience reproductive synchrony. Sexually mature males range more widely
      than females, but among them the dominant adult male has a relatively more
      limited range. His ranging and that of the subadult males reflect the local
      abundance of sexually attractive females. The other adult males tend to avoid
      these concentrations and focus on areas away from the dominant male. Females show
      philopatric tendencies. Male-biased sex ratios at birth give way to heavily
      female-biased sex ratios among adults. This suggests a net loss of males as they
      mature, due either to excess male mortality (e.g. by male mating competition),
      excess male dispersal from the population or a combination of both. We conclude
      that the orang-utan social organisation is best described as a loose community,
      showing neither spatial nor social exclusivity, consisting of one or more female
      clusters and the adult male they all prefer as mate.

PMID- 12065938
TI  - Cold stress in captive great apes recorded in incremental lines of dental
      cementum.
AB  - Incremental lines in dental cementum of museum specimens of 11 free-ranging great
      apes were compared to the respective structures in 5 captive specimens of known
      age-at-death, and with many known life-history parameters. While the dental
      cementum of the free-ranging apes was regularly structured into alternating dark
      and light bands, 4 out of 5 captive animals showed marked irregularities in terms
      of hypomineralized bands which could all be dated to the year 1963. Cementum
      preservation was insufficient in the fifth specimen and did not permit such a
      differentiation. All 4 captive apes had been kept in a zoo located in the
      northern hemisphere, where 1963 was characterized by an extremely cold winter.
      Since cold stress is a calcium-consuming process, the lack of available calcium
      in newly forming cementum could be responsible for the observed
      hypomineralization. The appositional growth characteristics of dental cementum
      serve as a record for such life-history events.

PMID- 12065939
TI  - An overview of the barbary macaque, Macaca sylvanus, vocal repertoire.
AB  - This study provides an overview of the vocalizations of Barbary macaques, Macaca
      sylvanus. Spectrographic displays of calls are presented along with photographs
      of the accompanying facial gestures. We give a general description of the
      contexts in which the different calls are uttered, with special regard to the age
      and sex of the caller. The vocal repertoire of Barbary macaques mainly consists
      of screams, shrill barks, geckers, low-frequency pants and grunts, with gradation
      occurring within and between call types. The spectrograms document that
      typically, Barbary macaques produce series of several consecutive calls. The
      influence of habitat, social structure and phylogenetic descent on the morphology
      of the repertoire and call diversity are discussed in comparison to other
      species.

PMID- 12065940
TI  - Parental failure in captive common marmosets (Callithrix jacchus): a comparison
      with tamarins.

PMID- 12065942
TI  - Population densities of primates in a Brazilian Atlantic forest.

PMID- 12065941
TI  - Surface remodelling of the facial skeleton in juvenile Macaca mulatta:
      implications for sexual dimorphism.

PMID- 12065943
TI  - Hand preference for feeding in captive Colobus guereza.

PMID- 12065944
TI  - Predation on a wild spectral tarsier (Tarsius spectrum) by a snake.

PMID- 12065945
TI  - Non-invasive fetal sex determination on fetal erythroblasts from the maternal
      circulation using fluorescence in situ hybridisation.
AB  - OBJECTIVE: The main purpose of this study was to evaluate the potential of a non
      invasive method for fetal sex determination in clinical practice using dual
      colour fluorescence in situ hybridisation (FISH) analysis. We evaluated the
      differences in nucleated red blood cell (NRBC) recovery from the maternal
      circulation using various slide preparation procedures following high-gradient
      magnetic cell separation (double MACS). METHODS: NRBCs were enriched from
      peripheral blood mononuclear cells of 63 pregnant women between 12 and 37 weeks
      of gestation by double MACS involving simultaneous CD14+ and CD45+ maternal cell
      depletion and CD71+ fetal cell enrichment. Isolated cells were analysed by dual
      colour FISH with X- and Y-specific probes. Before applying the FISH technique,
      cells were treated using three different protocols. Cells were either fixed in
      methanol:acetic acid (3:1) and dropped immediately onto glass slides (protocol 1)
      or treated with 75 mM KCl before resuspension in fixative (protocol 2).
      Alternatively, isolated cells were transferred onto glass slides and then treated
      using a method described in the literature (protocol 3). RESULTS: Using various
      slide preparation procedures, fixed cell numbers as well as the quality of slides
      differed significantly. Using protocol 1, fetal sex was well determined in 30
      cases, in 15 out of 17 male fetuses (1-13, mean 3 fetal cells were found among 5
      164, mean 50 maternal cells) and in 15 female fetuses (7-178, mean 56 fixed
      cells). On the other hand, interpretation difficulties occurred in 7 out of 8
      studied cases using protocol 2 due to a lack of cells or damage to the isolated
      cells. The highest recovery of fixed cells was achieved using protocol 3 (27-411,
      mean 186); fetal cells positive for the Y signal (2-12, mean 6) were detectable
      in all studied cases (n = 16). In 7 of the samples from women carrying female
      fetuses, we could only detect cells with two X signals (51-182, mean 103). All of
      the experiments were interpretable due to the presence of compact cells with well
      visible red and green signals. CONCLUSION: Our study revealed that using protocol
      3 as the post-MACS treatment results in improved NRBC recovery and enables a
      reliable prospective non-invasive fetal sex determination.

PMID- 12065946
TI  - Prenatal diagnosis in Rett syndrome.
AB  - BACKGROUND/AIM: Rett syndrome (RTT) is an X-linked neurodevelopmental dominant
      disorder that affects almost exclusively girls. The disease is mainly sporadic,
      caused by de novo mutations at MECP2 gene (Xq28), but a low percentage of
      familial cases have been reported. We present the results of RTT prenatal
      diagnosis in three families and discuss the usefulness of such analyses in
      diseases caused mainly by de novo mutations. METHODS: For adult individuals, DNA
      was extracted from peripheral lymphocytes; for fetus analysis it was obtained
      from cultured amniotic fluid or from chorionic biopsy specimens. Mutation
      detection at MECP2 gene was first carried out in the patients by SSCP/HD analysis
      and subsequent sequencing. Family studies and prenatal diagnoses were done by
      direct analysis of previously characterized patients' mutations using SSCP/HD or
      restriction analysis. RESULTS: Heterozygous mutations identified in the 3
      patients were: 1061del96bp, 473C-->T, and 763C-->T, respectively. Mutations were
      not present in the mothers' DNAs obtained from peripheral lymphocytes. None of
      the 3 fetuses analyzed carried the mutation of the affected sister. CONCLUSIONS:
      Recurrence within RTT families can be due to asymptomatic nonpenetrant carrier
      mothers or to parental germinal mosaicism for the MECP2 mutation. Since germline
      mosaicism can neither be predicted nor detected, families with 1 affected patient
      whose RTT-causing mutation has been previously identified can benefit from
      prenatal diagnosis which contributes to a decrease in the recurrence risk in a
      new pregnancy comparable to that of the normal population.

PMID- 12065947
TI  - Partial molar appearance of the placenta in trisomy 13.
AB  - Although molecular studies have shown that more than 90% of partial moles are
      secondary to diandric triploidy, there are some rare cases with tetraploidy or
      unspecified aneuploidies. We diagnosed 3 cases of partial mole presentation
      during the 2nd trimester of pregnancy with multiple fetal abnormalities. In all 3
      cases, cytogenetic studies showed trisomy 13. We present the cases and discuss
      the clinical and pathological aspects of the conditions presented as partial
      moles.

PMID- 12065948
TI  - Multifetal gestation--maternal and perinatal outcome of 112 pregnancies.
AB  - PURPOSE: Multifetal pregnancy reduction is a widespread "therapy" to diminish the
      risk of prematurity and adverse outcome for the survivors in higher order
      multiple gestation. The aim of our study was to determine the maternal and
      neonatal outcome of multifetal pregnancies under a conservative pregnancy
      management. STUDY DESIGN: A retrospective review of 112 multifetal pregnancies is
      presented. All higher order multiple pregnancies delivered after 25 weeks of
      gestation and managed at a single institution between 1982 and 1999 are included.
      RESULTS: Triplets, quadruplets and quintuplets were delivered at a mean
      gestational age of 31 + 5, 29 + 5 and 28 + 4 weeks, respectively. The perinatal
      mortality was 14 for triplets and 36 for quadruplets. No quintuplet died in the
      perinatal period. Respiratory distress syndrome occurred in 23% of triplets, 65%
      of quadruplets and 75% of quintuplets, intracranial hemorrhage was diagnosed in
      14% of triplets, 15% of quadruplets and 10% of quintuplets and retinopathy of
      prematurity was found in 10% of triplets, 9% of quadruplets and 25% of
      quintuplets. DISCUSSION: Despite a low neonatal mortality, morbidity of higher
      order multiple gestations remains significant. Mortality and morbidity are
      related to preterm delivery but do not exceed the rates of singletons or twins of
      an identical gestational age. Favorable prognostic landmarks are a gestational
      age >30 weeks and a number of fetuses per pregnancy < or =4. CONCLUSION: The
      risks of multifetal pregnancies are significant. Therefore, evidence-based
      counseling of couples seeking treatment for infertility and prevention of higher
      order multiple pregnancies through the prudent use of reproductive techniques
      attains paramount importance.

PMID- 12065949
TI  - Chorionic villus sampling: a 15-year experience.
AB  - The authors describe experiences gained over the period of 1984-1999 at two
      medical centers with chorionic villus sampling (CVS). Altogether 1,149 CVSs had
      been performed between the 10th and 32nd gestational weeks. Prior to 1993 the
      transcervical approach (TC-CVS), after 1994 the transabdominal method (TA-CVS)
      was used. Analysis of data collected within the framework of this study was based
      on the following factors: indications for sampling, complications and incidence
      of pregnancy loss. 91.6% of the CVSs were carried out for the purposes of
      cytogenetic examination of the fetus. Over the past few years an increasing
      number of procedures had been carried out for molecular-genetic tests (7.6% of
      the total number of cases). Though the primary indication for cytogenetic tests
      was the advanced age of the mother, a remarkable increase in the number of
      samplings had taken place for the purpose of examining "suspicious ultrasound
      findings", minor anomalies detected by ultrasound. In this group the proportion
      of pathological cases was significantly higher (14%) than in all the other
      samplings, carried out for other indications. This data in itself underlines the
      importance of ultrasound screening performed in the 18-20th weeks of gestation.
      Over the first half of the period being reviewed (1984-1993, TC-CVS), a fetal
      loss of 4.8% occurring within 3 weeks from the date of sampling, dropped to 1.7%
      in the period subsequent to year 1994 (TA-CVS). In cases of TA-CSV, both the
      complications and spontaneous abortions were fewer. In 74.1% of the cases
      studied, birth had taken place after the 37th week of gestation. Premature births
      (6.4%) and stillbirth rate (1.1%) did not exceed normal rates observed in the
      general population. On the basis of our results, it is safe to say that in
      prenatal diagnosis, TA-CVS is a real alternative method of mid-trimester
      amniocentesis and it is recommended for use at any stage of the pregnancy.

PMID- 12065950
TI  - Effects of antibiotic treatment on the concentrations of interleukin-6 and
      interleukin-8 in cervicovaginal fluid.
AB  - OBJECTIVE: We investigated to see the effect of antibiotics on interleukin (IL)-6
      and IL-8 in cervicovaginal fluid in patients with premature rupture of the
      membranes. STUDY DESIGN: Cervicovaginal fluid was sampled on admission and before
      delivery for measurement of IL-6 and IL-8 from 31 patients with less than 35
      weeks of gestation. Concentrations of IL-6 and IL-8 were measured by ELISA.
      RESULTS: The concentrations of IL-6 in cervicovaginal fluid in patients who were
      delivered because of clinical chorioamnionitis with antibiotics (n = 6) were
      significantly higher than in patients who were delivered because of active labor
      with (n = 14, p = 0.0133) and without antibiotics (n = 11, p = 0.0067). A
      significant change in the concentrations of IL-6 and IL-8 in cervicovaginal fluid
      was not observed in patients with and without antibiotics who were delivered
      because of active labor. CONCLUSIONS: The concentrations of IL-6 and IL-8 in
      cervicovaginal fluid might be influenced by the presence of clinical
      chorioamnionitis, but not by antibiotic administration.

PMID- 12065951
TI  - Umbilical cord cyst in a monochorionic twin pregnancy: an experiment of nature
      for the treatment of twin-twin transfusion syndrome.
AB  - A patient with a monochorionic twin pregnancy developed signs of twin-twin
      transfusion syndrome from 18 weeks of gestational age. At 23 weeks, an umbilical
      cord cyst and absent diastolic umbilical artery flow were noted in the donor
      twin. The pregnancy progressed uncomplicated until term and resulted in vaginal
      delivery of 2 healthy male babies at 38 weeks of gestational age. We hypothesize
      that the compression on the umbilical arteries of the donor twin by the umbilical
      cord cyst has resulted in a partial "compensation" of the twin-twin transfusion
      phenomenon.

PMID- 12065952
TI  - Congenital bowing of long bones: prenatal ultrasound findings and diagnostic
      dilemmas.
AB  - OBJECTIVE: Bowing of the long bones can be easily detected on antenatal
      ultrasound screening, but it is a nonspecific sign that can be associated with a
      variety of conditions, each denoting a different prognosis. Among these
      conditions, three well-differentiated bone dysplasias share bowed long bones as a
      main clinical manifestation. Campomelic dysplasia and Stuve-Wiedemann syndrome
      are characterized by a poor prognosis. Conversely, the overall prognosis of
      children affected with kyphomelic dysplasia is good, the intelligence and motor
      development are normal and the radiological abnormalities tend to improve and
      regress with age. CASE REPORT: We report a case of prenatal detection of short
      and bowed femora at the 22nd week of gestation. Careful US examination as well as
      in utero X-ray of the skeleton allowed the exclusion of campomelic dysplasia. In
      the absence of an unambiguous diagnosis, the pregnancy was continued. At birth,
      the child presented with clinical and radiological features consistent with a
      diagnosis of kyphomelic dysplasia. CONCLUSION: This case illustrates the
      difficulties in making an accurate diagnosis and consequently giving a prognosis
      when isolated femoral bowing is found on fetal ultrasound examination.

PMID- 12065954
TI  - A fetus with trisomy 9p and trisomy 10p originating from unbalanced segregation
      of a maternal complex chromosome rearrangement t(4;10;9).
AB  - Complex chromosome rearrangements are only rarely seen in constitutional
      karyotypes. A case of prenatally detected trisomy 9p with trisomy 10p originating
      from adjacent segregation of a maternal complex chromosome rearrangement is
      reported. Ultrasound examination at 18 weeks of gestation showed cleft lip
      palate, club feet, structural anomalies of the cerebellum and cystic kidneys.
      Cytogenetic analysis of amnion cells revealed a female fetus with 47,XX,+der(9).
      FISH analyses together with parental karyotyping demonstrated the fetal
      additional chromosome to originate from malsegregation of a maternal complex
      chromosomal rearrangement. The mother is carrier of a balanced translocation
      t(4;10;9) (q12; p11;q13). Postmortem examination of the fetus showed nose
      anomalies, cleft lip palate, low set ears, club feet, lung anomalies, cystic
      kidney and aplasia of the uterus. Reporting of such rare cases is important in
      order to enable this information to be used for genetic counselling in similar
      situations.

PMID- 12065953
TI  - Maternal-fetal factors that affected Doppler waveform analysis in a patient
      undergoing hemodialysis.
AB  - Pregnancy in women having chronic renal insufficiency and undergoing hemodialysis
      is a rare event with a poor outcome. This is the 1st case in whom pre- and
      posthemodialysis fetal renal artery Doppler flow velocimetry was used in
      conjunction with fetal blood sampling which was performed to assess fetal
      karyotype and blood chemistry. Uteroplacental Doppler measurements were also
      performed, and a close correlation between maternal-fetal blood creatinine and
      urea nitrogen levels and fetal renal, umbilical, and uterine artery resistance
      indexes was observed.

PMID- 12065955
TI  - Natural history of 70 fetuses with a prenatally diagnosed orofacial cleft.
AB  - OBJECTIVE: This study is an analysis of neonatal outcome in 70 fetuses diagnosed
      over a 10-year period as having cleft lip with or without cleft palate (CL-P) by
      ultrasonographic examination. METHODS: We describe the natural history of these
      70 fetuses with orofacial clefts and select those who may be candidates for fetal
      surgery. The sonograms of 70 fetuses with orofacial clefts were evaluated for the
      nature of the CL-P and for the nature of the associated anomalies. Additionally,
      karyotyping was performed in 63 of 70 patients (90%). RESULTS: The frequency of
      additional anomalies and the mortality rate varied with the type of cleft. Also,
      the frequency and type of chromosomal abnormalities varied with the type of
      cleft. The overall mortality rate was 63% (n = 44). 3 of the surviving 26 fetuses
      had severe associated anomalies. In 13 of the remaining 23 cases, the fetal age
      at diagnosis (> or =22 weeks) excluded the fetuses from the potential benefits of
      fetal intervention. CONCLUSION: Of 70 fetuses with prenatally diagnosed orofacial
      clefts, only 10 (14%) were candidates for fetal CL-P surgery.

PMID- 12065957
TI  - Prenatal diagnosis of pial-superficial arteriovenous malformation.
AB  - In the newborn, cerebral pial arteriovenous malformation has been recognized as a
      cause of congestive heart failure. Prenatal diagnosis allows early medical
      treatment of cardiac failure and increases the chance of successful
      neuroradiological intervention. This paper highlights the importance of careful
      prenatal cerebral examination in cases of cardiac ventricle enlargement.

PMID- 12065956
TI  - Preterm premature rupture of membrane and twin-to-twin transfusion syndrome
      before 20 weeks: a favourable outcome.
AB  - We describe a monochorionic twin gestation with a severe twin-to-twin transfusion
      syndrome associated with a preterm premature rupture of membranes at 20 weeks of
      gestation in the polyhydramniotic sac. The pregnancy was managed expectantly and
      outcome was favourable for the 2 neonates. We discuss how these two severe
      pathologies seem to counteract each other by compensations of their symptoms.

PMID- 12065958
TI  - The relationship between consumption, and use and abuse of drugs and relatives
      (or the family in general).

PMID- 12065959
TI  - Association between the engagement of relatives in a behavioural group
      intervention for smoking cessation and higher quit rates at 6-, 12- and 24-month
      follow-ups.
AB  - OBJECTIVE: To assess the effectiveness of a behavioural group intervention for
      smoking cessation, which included as its most original feature the recommendation
      to participate with a relative or close friend. METHODS: A total of 1,060
      subjects entered the programme, which consisted of 9 group sessions over a period
      of 5 weeks. The intervention consisted of a modified version of the Five-Day
      Plan, the main differences being the use of behavioural therapy techniques and
      small group work, and the addition of 4 weekly booster sessions. About two thirds
      of the participants came with a relative or close friend. Long-term abstinence
      from smoking was assessed with follow-up telephone interviews. RESULTS: Very few
      subjects were lost to follow-ups (9.2% at 6 months, 9.7% at 1 year, 10.8% at 2
      years). The observed quit rates were 42.6% at 6 months, 35.5% at 1 year and 32%
      at 2 years. When considering as smokers all subjects who were lost to follow-ups,
      quit rates were also satisfactory (38.7% at 6 months, 32.1% at 1 year and 28.6%
      at 2 years). The main predictors of a good outcome were being male, smoking less
      than 20 cigarettes per day, having started smoking after 18 years of age, having
      made previous quitting attempts, not having a history of unsuccessful
      participation to smoking cessation interventions and attending the sessions with
      a relative or close friend. DISCUSSION: Although some limitations inherent in the
      design of our study suggest caution in interpreting the results and in making
      comparisons, the long-term effectiveness of the intervention was satisfactory.
      The inclusion of a relative or close friend appeared useful. This simple and
      inexpensive strategy may deserve recommendation, though in the future it should
      be tested in controlled trials.

PMID- 12065960
TI  - Smoking habit among the relatives of patients with serious smoking-related
      disorders.
AB  - OBJECTIVE: To assess smoking habit and awareness of smoking as a potential cause
      of disease among relatives of patients with serious smoking-related disorders.
      DESIGN AND SETTING: A survey using a face-to-face interview-assisted
      questionnaire at the Ege University Hospital between October 1998 and March 1999.
      SUBJECTS: We interviewed 242 relatives of patients with serious smoking-related
      disorders, of whom 56.6% were female and 43.4% male. The mean age was 41.2 +/-
      13.2 years (15-75). One relative per patient completed the questionnaire and the
      chosen relative took care of the patient during his illness and accompanied him
      during hospital visits. MAIN OUTCOME MEASURES: We assessed the relationship
      between smoking habit and the perception of smoking as a potential cause of
      illness by the relatives. Statistical analysis was performed by chi(2) test.
      RESULTS: The prevalence of smoking among relatives was 37.6% [49.5% males (n =
      105) and 28.5% females (n = 137), p = 0.0003] and an additional 20.2% were ex
      smokers. Of the relatives, 86.4% knew that the diseases were directly related to
      smoking, and 37.8% of these people were smokers and 21.5% ex-smokers. Only 7.2%
      reported that they had quit smoking after being influenced by the diseases of the
      patients. The decision to quit was statistically unrelated to the awareness of
      smoking as the cause of disease. Of all the relatives, 69.2% had tried to quit at
      least once, 86.8% considered quitting, and 89.0% considered using professional
      help for smoking cessation. CONCLUSION: The findings show that even though this
      group of smokers is aware of the harmful effects of smoking they cannot
      successfully quit smoking; however, the majority reconsider quitting and
      receiving professional help.

PMID- 12065961
TI  - The role of family and partnership in recovery from alcohol dependence:
      comparison of individuals remitting with and without formal help.
AB  - The aim of this study was to analyse the role of family and partnership in
      remission from alcohol dependence in treated (n = 50) and untreated (n = 115)
      individuals. Standardised questionnaires to assess social support, social
      pressure, coping behaviour, and self-efficacy to stay remitted were used. In both
      media-solicited samples, social support increased from the pre- to the post
      resolution period and was stated as an important resolution maintenance factor.
      Remitters with formal help experienced more partnership conflicts prior to
      remission and tended to experience more social pressure from their partner.
      Social support and social pressure from the family and partner were related to an
      increase in cognitive coping, as hypothesised, however, only in remitters without
      formal help, whereas an inverse relationship was found in formal help seekers.
      Implications for alcohol-related interventions are discussed.

PMID- 12065962
TI  - Screening for paternal alcoholism: reliability of a German version of the F
      SMAST.
AB  - The development of screening instruments for the detection of paternal alcoholism
      is of both clinical and research interest. F-SMAST, an adapted version of the
      Short Michigan Alcoholism Screening Test (SMAST), has proven to be a reliable and
      valid instrument for the assessment of an individual's father's drinking history.
      The present investigation examines the reliability of a German version of the F
      SMAST. Internal consistency and test-retest stability (Pearson correlation
      coefficients on unweighted total scores; kappa statistics and Yule's Y of the
      individual items) are evaluated in a sample of undergraduates (n = 202). Internal
      consistency of the F-SMAST is re-evaluated in a second study by analysing the
      responses of alcohol-dependent in-patients (n = 205). The German version of the F
      SMAST exhibited excellent reliability in terms of internal consistency and test
      retest stability of the unweighted total scores. Test-retest agreement of the
      individual items was in the acceptable range. Taking into account the lifetime
      prevalence of alcoholism and several background variables (e.g. marital status
      and number of real children) a cut score of 6 or 7 on the F-SMAST seems
      appropriate for the detection of paternal alcoholism.

PMID- 12065963
TI  - Ecstasy-induced psychotic disorder: six-month follow-up study.
AB  - OBJECTIVE: To describe the psychiatric symptoms manifested by persons diagnosed
      for the first time as having ecstasy-induced psychotic disorder and to explore
      the evolution of their symptoms over a 6-month period. DESIGN: Observational
      study with a 6-month follow-up. METHOD: The subjects studied were 32 ecstasy
      consumers who were treated at two drug-dependency outpatient centers for
      hallucinatory-delusive manifestations and who were diagnosed as having ecstasy
      induced psychotic disorder according to DSM-IV criteria. For the assessment of
      the intensity of the syndrome and its follow-up, the Brief Psychiatric Rating
      Scale (BPRS), the Hamilton Depression Rating Scale (HDRS) and the Clinical Global
      Impression (CGI) were used at the outset and after 1, 3 and 6 months. All
      subjects received treatment with olanzapine. RESULTS: The treatment program was
      completed by 96.9% of the patients. At the baseline assessment, a high incidence
      of symptoms of a severe psychiatric disorder was observed. From the first month
      the psychotic symptoms (BPRS) were considerably reduced with treatment, with the
      most severe positive symptoms remitting in the first 3 months. The three
      assessment indicators (BPRS, HDRS and CGI) showed a statistically significant
      clinical reduction over the 6 months of the assessment period. Furthermore, no
      relevant side effects were noted. CONCLUSIONS: In its initial manifestations, a
      drug-induced psychotic syndrome includes marked symptoms meeting the criteria of
      a severe psychotic disorder, with the presence of considerable positive and
      negative symptoms. Olanzapine has been shown to be very effective in these
      situations and its use is suggested as first-choice therapy.

PMID- 12065964
TI  - Where have all the young girls gone or where do all the men come from? Change and
      lack of change in demographic characteristics of the norwegian heroin user
      population.
AB  - A rough estimate indicates that women amount to one third of the heroin user
      population in Norway. However, among the youngest users females account and have
      accounted for a larger proportion. Given this greater representation of females
      in the younger age groups one would expect that the gender difference in the
      general population of users would be reduced over time due to a cohort effect.
      However, the ratio of male to female users has remained stable. The prevailing
      explanation for this stability is based on the claim that women are more likely
      to overcome their abuse. This paper addresses both the basis for the assumption
      of a missing cohort effect and examines an alternative explanation linked to the
      way into abuse rather than the way out. The study primarily draws upon two
      distinct data sources. The first body of material consists of interviews carried
      out in the period 1993-1997 with people attending the only needle exchange
      service in Oslo. The second data source consists of police records, which provide
      the number of persons arrested each year in the period 1984-1997 for using,
      possessing or selling heroin distributed by age and gender. We find that the age
      of injection debut has increased and that this is especially true for male users.
      Applying a simple quantitative model, the effect a change in recruitment may have
      on the male-to-female ratio is analysed. The results indicate that a higher debut
      age may have contributed to stabilizing the gender gap. The finding suggests that
      more research is needed on the conditions of recruitment in order to better
      predict the future population demographics and to avoid hasty and incorrect
      conclusions.

PMID- 12065965
TI  - Use of MDMA and other illicit drugs by young adult males in northern Spain. A
      five-year study.
AB  - AIM: To measure the prevalence of 3,4-methylenedioxymethamphetamine (MDMA) and
      other drug use in young males entering compulsory military service in Asturias
      (northern Spain) and to define trends in MDMA use in this group during the period
      from 1995 to 1999. We also sought to determine whether MDMA users have distinct
      personality features or higher levels of sensation seeking. METHODS: 3,634
      conscripts [mean age (SD) = 20.19 years (2.52)] who entered military service
      during the period between 1995 and 1999 were evaluated using the World Health
      Organization (WHO) questionnaire for drug consumption, the Eysenck Personality
      Questionnaire-A (EPQ-A), and the Zuckerman Sensation Seeking Scale. RESULTS AND
      CONCLUSIONS: The prevalence of lifetime, previous year and previous month MDMA
      use among military recruits between 1995 and 1999 was 10.9, 7.8 and 4.5%, ranking
      fifth among illicit drugs ever used. Once individuals used MDMA for the first
      time, they were likely to use it again, with 71% of individuals who had ever used
      MDMA reporting that they had used it during the past year (ranking second only to
      hallucinogens), and 41% reporting having used it in the last month. Compared to
      recruits who had never used MDMA (but who may have used other illicit drugs),
      MDMA users had a more extensive drug abuse history. Recruits who had used MDMA
      during the year prior to study had significantly higher scores on the Neuroticism
      and Psychoticism Subscales of the EPQ-A, and reported higher levels of sensation
      seeking.

PMID- 12065966
TI  - Susceptibility of Streptococcus mutans and Streptococcus sobrinus to cell wall
      inhibitors and development of a novel selective medium for S. sobrinus.
AB  - Representative strains of Streptococcus mutans and Streptococcus sobrinus showed
      differences in susceptibility to members of the monobactam group of beta-lactam
      antibiotics: S. sobrinus was less sensitive than S. mutans. The minimum
      inhibitory concentrations of aztreonam (AZT) and carumonam, both of which belong
      to this group, were 2,000 microg/ml for S. sobrinus and 125 microg/ml for S.
      mutans. Further addition of fosfomycin, bacitracin and sodium chloride to Mitis
      Salivarius agar (MS) supplemented with AZT resulted in growth inhibition of S.
      mutans and oral streptococci other than S. sobrinus, and was therefore used as a
      selective medium for S. sobrinus (MS-SOB medium). The average growth recovery of
      laboratory and clinically isolated strains of S. sobrinus on MS-SOB medium was
      74.1% compared to that on MS medium. Seventy-eight percent of clinical samples in
      which S. sobrinus was detected yielded pure growth of S. sobrinus on MS-SOB
      medium.

PMID- 12065968
TI  - Effect of a lactose-containing sweetener on root dentine demineralization in
      situ.
AB  - Since lactose has been used as an excipient in powdered sweeteners, we evaluated
      its effect on dentine demineralization, in an in situ crossover study. Twelve
      adult volunteers wore palatal appliances containing 4 blocks of bovine root
      dentine, which were submitted 4 times a day to: distilled water (negative
      control), aqueous solution of powdered sweetener (Zero Cal); experimental group),
      1.5% lactose solution (active group), 1.5% sucrose solution (positive control).
      After 15 days, microhardness was determined on dentine surface (SMH) and on the
      sectioned blocks (CSMH). All groups presented statistical differences in SMH
      before and after the treatments; water increased, while sweetener, lactose and
      sucrose decreased SMH. By CSMH, the only significant difference was observed
      after sucrose treatment. The data suggest that sweeteners containing lactose as a
      bulking agent may be cariogenic for root dentine.

PMID- 12065967
TI  - Transmission of mutans streptococci in adults within a Chinese population.
AB  - The purpose of this study was to investigate whether there was transmission
      between adults in Chinese families using chromosomal DNA fingerprinting. Plaque
      samples were obtained from buccal and occlusal surfaces of 11 married couples.
      The colonization levels of mutans streptococci were estimated as colony-forming
      units per milliliter, and caries experience was scored by decayed, missing and
      filled teeth. Information about medical history, diet regimes and age at marriage
      was obtained. The isolates were serotyped by biochemical test and genotyped using
      the restriction endonuclease HaeIII. The procedure was repeated after 3 months.
      The results showed that 1 couple had the same genotype of mutans streptococcus at
      the first examination, but this could not be repeated for the husband who had
      lost his mutans streptococci at the second examination. On the contrary, another
      couple that did not have the same mutans streptococcal genotype at the beginning
      had the same genotype after 3 months. No matching of genotypes was observed
      within 8 couples. In 1 male, no mutans streptococci were detected, therefore that
      couple was not considered. These data indicate that spouses had a chance to be
      infected by strains of mutans streptococci from another person. The results
      suggest that there may be transmission between adults in Chinese families, but it
      may be difficult for mutans streptococci to colonize another mouth permanently.

PMID- 12065969
TI  - Caries prevalence among 6- to 16-year-old students in Jamaica 12 years after the
      Introduction of salt fluoridation.
AB  - The aim of this descriptive cross-sectional study was to evaluate the caries
      prevalence among 6- to 16-year-old students in a rural community in Jamaica,
      where salt fluoridation was introduced in 1987. Data were obtained from dental
      examinations of 1,558 students in 1999. The mean (SD) dmfs/DMFS values were 7.9
      (10.7) for the 6-year-old children, 4.1 (4.9) for the 12-year-old students and
      8.2 (8.1) for the 15-year-olds; mean (SD) dmft/DMFT scores were 3.2 (3.5), 2.2
      (2.1) and 3.8. (3.3), respectively. An Unmet Restorative Index of 88-99.9% was
      observed. Opacities due to fluorosis were recorded for 48% of the children
      examined. The results indicate a reduced caries prevalence for all age groups
      since salt fluoridation began. However, since various forms of fluoride might
      have contributed to the reduction, conclusions concerning salt fluoridation as
      the main factor must be drawn with caution. The effectiveness of salt
      fluoridation in Jamaica should be re-examined more closely.

PMID- 12065971
TI  - Presidential address: pathomechanism of myelopathy and radiculopathy from the
      viewpoint of blood flow and cerebrospinal fluid flow including a short historical
      review.

PMID- 12065972
TI  - New approaches to magnetic resonance imaging of intervertebral discs, tendons,
      ligaments, and menisci.
AB  - This review article discusses new magnetic resonance techniques for imaging
      collagen containing structures such as intervertebral discs, tendons, and
      ligaments. The semisolid collagen in tendons and ligaments is not normally
      demonstrable with magnetic resonance imaging but may be visualized with magic
      angle imaging and other techniques. This allows these structures to be studied
      with methods used for other tissues and organs. The ordered nature of collagen
      provides a directional signature for the tissues that may be of diagnostic value.
      Solute transport in these avascular or partially avascular structures can be
      observed with gadolinium chelates. The time scale of this process is much slower
      than for other tissues of the body. Solid state imaging techniques applied in
      applied in material sciences may provide other new approaches to diagnosis of
      disease in these structures.

PMID- 12065973
TI  - Long-term functional outcome of pedicle screw instrumentation as a support for
      posterolateral spinal fusion: randomized clinical study with a 5-year follow-up.
AB  - STUDY DESIGN: A prospective randomized clinical study with a 5-year follow-up.
      OBJECTIVES: To analyze the long-term effect of supplementary transpedicular screw
      fixation on reoperation rate and functional outcome. SUMMARY OF BACKGROUND DATA:
      Within the past few years the benefit of supplemental pedicle screw fixation has
      been questioned as a standard procedure in lumbar spinal fusion surgery. The long
      term effect of supplemental pedicle screw fixation is still unknown. METHODS:
      From 1992 through 1994 a total of 129 patients with severe chronic low back pain
      were randomly selected for either supplemental pedicle screw fixation
      (instrumented) or no pedicle screw instrumentation (noninstrumented)
      posterolateral spinal fusion. The Dallas Pain Questionnaire, Low Back Pain Rating
      Scale, and a questionnaire concerning work status assessed the outcome. RESULTS:
      A 5-year follow-up of 93% showed that the instrumented group had a 25%
      reoperation rate (removal of instrumentation with and without second fusion)
      compared with a reoperation rate of 14% in the noninstrumented group (fusion and
      decompression) (P < 0.03). A total of 51% were capable of working after 5 years
      compared with 40% before surgery. There was no difference in work capacity
      between the two groups at any point of observation. Overall, there was no
      significant difference between the instrumented and noninstrumented groups in
      regard to functional outcome as measured by both the Dallas Pain Questionnaire
      and Low Back Pain Rating Scale. When analyzing diagnostic subgroups at the 5-year
      follow-up, patients with isthmic spondylolisthesis had a significantly better
      outcome by use of a posterolateral fusion without supplemental instrumentation
      compared with an instrumented fusion (P < 0.03). However, patients with primary
      degenerative instability improved significantly more when instrumentation
      supported the posterolateral spinal fusions (P < 0.02). To the question "was it
      worth it?" 67% answered "yes" in the instrumented group whereas 70% did so in the
      noninstrumented groups (not significant). CONCLUSION: The long-term functional
      outcome of posterolateral spinal fusion improved significantly for boththose with
      and without pedicle screw instrumentation, with a global 70% satisfaction
      reported by the patients. Patients with isthmic spondylolisthesis Grades 1 and 2
      with noninstrumented fusion had superior long-term outcomes after posterolateral
      spinal fusion in comparison with an instrumented fusion. In contrast, patients
      diagnosed as having primary degenerative instability improved significantly when
      the posterolateral fusion was supported by instrumentation. In actuality, pedicle
      screw instrumentation increased reoperation rate compared with noninstrumented
      posterolateral fusion.

PMID- 12065974
TI  - Increased nerve and blood vessel ingrowth associated with proteoglycan depletion
      in an ovine anular lesion model of experimental disc degeneration.
AB  - STUDY DESIGN: Nerves and blood vessel distribution in discs were localized
      immunohistochemically and correlated with the proteoglycan contents of normal and
      degenerate disc tissues. OBJECTIVE: The aim of the present study was to
      systematically evaluate whether nerve and blood vessel ingrowth was associated
      with depletion of disc proteoglycans and degenerative changes in an established
      experimental model of disc degeneration. SUMMARY OF BACKGROUND DATA: Animal
      models of disc degeneration, allowing longitudinal study of pathogenic
      mechanisms, are limited. The ovine model enables systematic monitoring of blood
      vessel and nerve ingrowth during the development of disc degeneration after
      injury to the anulus fibrosus. METHODS: Merino sheep received a controlled left
      anterolateral surgical defect in the outer anulus fibrosus of the L1-L2 and L3-L4
      discs (lesion group); sham-operated controls received the retroperitoneal
      anterolateral approach only. Animals were killed 3, 6, 12, and 26 months
      postoperation, and the discs were collected for histology and compositional and
      morphologic analyses. Sagittal tissue sections were stained with toluidine blue
      and hematoxylin and eosin; Type IV collagen immunolocalization visualized blood
      vessel ingrowth, and nerves were immunolocalized using monoclonal antibodies to
      growth-associated protein (GAP-43), protein gene product 9.5, and glial
      fibrillary acidic protein. RESULTS: Compositional and histologic results
      demonstrated early focal depletion 3-12 months postoperation of glycosaminoglycan
      associated with lesion development, increased blood vessel and nerve ingrowth,
      and infiltration of cells from the outer anulus fibrosus along the plane of the
      original defect. Blood vessel numbers in the outer to mid third of the anulus
      fibrosus were elevated in the lesion discs 3-6 months postoperation reaching a
      maximum at 12 months postoperation; nerves immunoreactive with protein gene
      product 9.5 (also maximal at 12 months postoperation) were often found associated
      (but not exclusively) with blood vessels, and some nerves were also reactive with
      GAP-43 and glial fibrillary acidic protein, but only at 12 months postoperation.
      CONCLUSIONS: Nerve and blood vessel ingrowth into the anulus fibrosis were
      strongly associated with proteoglycan depletion. The ovine anular lesion model of
      disc degeneration is a useful experimental model for the systematic evaluation of
      nerve and blood vessel development after anular injury.

PMID- 12065975
TI  - Effect of tail suspension (or simulated weightlessness) on the lumbar
      intervertebral disc: study of proteoglycans and collagen.
AB  - STUDY DESIGN: An experiment to measure the proteoglycan and collagen content of
      the lumbar intervertebral discs of rats that had been tail-suspended for up to 4
      weeks. OBJECTIVES: To determine the effect of tensile force (or simulated
      weightlessness) on the intervertebral disc. SUMMARY OF BACKGROUND DATA: During
      space flight the intervertebral disc experiences low compressive force (because
      of so-called "weightlessness"), which, in turn, produces, among other things, low
      hydrostatic pressure acting on the disc cells. Although disc cells respond (in
      vitro) to changes in hydrostatic pressure, it is unclear what effect low levels
      of hydrostatic pressure have in vivo and whether they lead to a degenerative
      catabolic process. The rat tail-suspension model is appropriate for studying the
      effects of tensile force on the disc. The disc (especially the anulus) is
      subjected to tension during various body movements (e.g., bending stretches the
      posterior anulus, and twisting tensions the whole anulus). METHODS: Thirty-two
      Sprague-Dawley rats were tail-suspended for either 2 weeks (16 rats) or 4 weeks
      (16 rats). Sixteen other rats were left unsuspended for 4 weeks; these were used
      as controls. At the end of 2 or 4 weeks, as appropriate, the rats were killed and
      their lumbar spines were removed. In each rat the six lumbar discs were bisected
      and the discs (anulus and nucleus together) were carefully removed. The six
      lumbar discs from one rat were pooled with the six lumbar discs of a second
      matching rat (i.e., from the same group) to give one sample. The disc samples
      were then assessed using enzyme-linked immunosorbent assays. RESULTS: There was a
      35% statistically significant decrease in proteoglycan content going from the
      control group down to the 4-week group, but no significant differences between
      the control group and the 2-week group or between the 2-week group and the 4-week
      group. There were no statistically significant differences between the three
      groups for collagen I or collagen II. CONCLUSIONS: These findings clearly
      establish a link between decreased proteoglycan content and tension on the disc,
      as modeled by the tail-suspended rat.

PMID- 12065976
TI  - Comparative gene expression profiling of normal and degenerative discs: analysis
      of a rabbit annular laceration model.
AB  - STUDY DESIGN: A rabbit annular laceration model was used to investigate
      intervertebral disc gene expression in normal and lacerated discs. OBJECTIVES: To
      determine and compare the pattern of expression of potentially important genes in
      normal and lacerated discs and to determine if the changes in gene expression
      were similar to human degenerative discs. SUMMARY OF BACKGROUND DATA: Little is
      known regarding gene expression in normal or degenerating disc tissue. METHODS:
      Eighteen rabbits were subjected to annular laceration of the L1-L2 and L2-L3
      discs while two rabbits served as sham controls. Control and lacerated discs were
      harvested 1 week, 3 weeks, and 6 weeks following surgery and subjected to
      histologic examination and gene expression analysis using the reverse
      transcription-polymerase chain reaction (RT-PCR). The genes studied included
      collagen Type I (Col I), collagen Type II (Col II), decorin, fibronectin (FN),
      interleukin-1a (IL-1alpha), bone morphogenetic protein 2 (BMP-2), Fas, matrix
      metalloproteinase 1 (MMP-1), matrix metalloproteinase 9 (MMP-9), matrix
      metalloproteinase 13 (MMP-13), and tumor necrosis factor (TNF). Expression levels
      of each gene were normalized to that of glyceraldehyde-3-phosphate dehydrogenase
      (GADPH), a constitutively expressed gene. RESULTS: Histology confirmed
      progressive degeneration of the discs over the 6-week study period. Different
      patterns of gene expression were observed in control and lesioned discs. Annular
      laceration caused a marked upregulation (two- to eightfold) of the expression of
      Col I, Col II, FN, MMP-1, MMP-9, MMP-13, and Fas genes, whereas that of BMP-2, IL
      1alpha, and TNF genes was unaffected. Expression of the decorin gene was
      downregulated approximately sixfold after annular laceration. CONCLUSION: Annular
      laceration in this animal model resulted in marked changes in gene expression.
      Upregulation of gene expression was observed for some molecules found at high
      concentration in human degenerated discs, suggesting similarities to human disc
      degeneration at the molecular level. This supports the need for further study of
      the genes found to be activated by annular laceration.

PMID- 12065977
TI  - Biomechanical evaluation of an injectable calcium phosphate cement for
      vertebroplasty.
AB  - STUDY DESIGN: Destructive biomechanical tests using fresh cadaveric thoracolumbar
      vertebral bodies. OBJECTIVES: To evaluate the compression strength of human
      vertebral bodies injected with a new calcium phosphate (CaP) cement with improved
      infiltration properties for augmentation of the vertebral bodies before
      compression fracture and also for vertebroplasty in comparison with
      polymethylmethacrylate (PMMA) injection. SUMMARY OF BACKGROUND DATA:
      Vertebroplasty is the percutaneous injection of PMMA cement into the vertebral
      body. While PMMA has high mechanical strength, it cures fast and thus allows only
      a short handling time. Other potential problems of using PMMA injection may
      include damage to surrounding tissues by a high polymerization temperature or by
      the unreacted toxic monomer, and the lack of long-term biocompatibility. Bone
      mineral cements, such as calcium carbonate and CaP cements, have longer working
      time and low thermal effect. They are also biodegradable while having a good
      mechanical strength. However, the viscosity of injectable mineral cements is
      high, and the infiltration of these cements into vertebral body has been
      questioned. Recently, the infiltration properties of a CaP cement have been
      significantly improved, which is ideal for the transpedicular injection to the
      vertebral bodies for vertebroplasty or augmentation of osteoporotic vertebral
      body strength. METHODS: The bone mineral densities of 30 vertebral bodies (T2-L1)
      were measured using dual-energy x-ray absorptiometry. Ten control specimens were
      compressed at a loading rate of 15 mm/min to 50% of their original height. The
      other specimens had 6 mL of PMMA (n = 10) or the new CaP (n = 10) cement injected
      through the bilateral pedicle approach before being loaded in compression.
      Additionally, after the control specimens had been compressed, they were injected
      with either CaP (n = 5) or PMMA (n = 5) cement using the same technique, to
      simulate vertebroplasty. Loading experiments were repeated with the displacement
      control of 50% vertebral height. Load to failure was compared among groups and
      analyzed using analysis of variance. RESULTS: Mean bone mineral densities of all
      five groups were similar and ranged from 0.56 to 0.89 g/cm2. The size of the
      vertebral body and the amount of cement injected were similar in all groups. Load
      to failure values for PMMA, the new CaP, and vertebroplasty PMMA were
      significantly greater than that of control. Load to failure of the vertebroplasty
      CaP group was higher than control but not statistically significant. The mean
      stiffness of the vertebroplasty CaP group was significantly smaller than control,
      PMMA, and the new CaP groups. The mean height gains after injection of the new
      CaP and PMMA cements for vertebroplasty were minimal (3.56% and 2.01%,
      respectively). CONCLUSION: Results of this study demonstrated that the new CaP
      cement can be injected and infiltrates easily into the vertebral body. It was
      also found that injection of the new CaP cement can improve the strength of a
      fractured vertebral body to at least the level of its intact strength. Thus, the
      new CaP cement may be a good alternative to PMMA cement for vertebroplasty,
      although further in vivo animal and clinical studies should be done. Furthermore,
      the new CaP may be more effective in augmenting the strength of osteoporotic
      vertebral bodies for preventing compression fractures considering our
      biomechanical testing data and the known potential for biodegradability of the
      new CaP cement.

PMID- 12065979
TI  - Point of view.

PMID- 12065978
TI  - Functional outcome and radiographic correction after spinal osteotomy.
AB  - STUDY DESIGN: A prospective clinical trial to study the radiographic parameters
      and functional outcome in patients undergoing spinal osteotomy. OBJECTIVES: To
      determine whether correction of specific radiographic parameters is associated
      with improved functional outcome. SUMMARY OF BACKGROUND DATA: Although vertebral
      osteotomies have been shown to improve functional outcome in patients with spinal
      deformity, no prospective reports have studied whether correction of specific
      radiographic parameters is associated with improvement in functional outcome.
      METHODS: Eighty-three patients with fixed sagittal and/or coronal deformity were
      followed over a 7-year period. Patients were evaluated clinically and
      radiographically and completed a SF-36 Health Survey and American Academy of
      Orthopedic Surgeons Modems Instrument questionnaire. Spearman correlation
      analysis was used to determine the association between correction of radiographic
      parameters and functional outcome. RESULTS: Mean preoperative lumbar lordosis
      measured -14.2 degrees (i.e., kyphosis) with an average postoperative correction
      of 27.9 degrees. Mean preoperative lumbar scoliosis measured 40.1 degrees with an
      average postoperative correction of 15.1 degrees. Mean preoperative plumb
      sagittal and coronal plane alignment was 8.37 cm and 4.22 cm, respectively; after
      surgery they improved to 3.33 cm and 2.31 cm, respectively. A significant
      association was found between sagittal angular correction and physical function
      (P = 0.034) and role-physical (P = 0.01) when postoperative lumbar lordosis was
      >25 degrees. A significant association was also found between plumb coronal
      correction and physical function (P = 0.041), vitality (P = 0.05), and social
      function (P = 0.047) when postoperative plumb coronal alignment was <2.5 cm.
      CONCLUSIONS: Correction of sagittal and coronal deformity is important in the
      treatment of spinal deformity. A significant association was found between
      outcomes and radiographic correction of coronal and/or sagittal deformity if
      postoperative sagittal lordosis was >25 degrees and if postoperative plumb
      coronal alignment was <2.5 cm. Therefore, these radiographic parameters should be
      the goal of a spinal osteotomy. The surgery has a relatively high complication
      rate.

PMID- 12065980
TI  - Pathogenesis of sciatic pain: a study of spontaneous behavior in rats exposed to
      experimental disc herniation.
AB  - STUDY DESIGN: A new way to study pain in experimental animals without handling of
      the animals and based on registration of spontaneous behavior using video
      recordings. OBJECTIVES: To evaluate if experimental disc herniation in the rat
      may induce changes in spontaneous behavior. SUMMARY OF BACKGROUND DATA: The
      knowledge regarding the basic pathophysiologic mechanisms of sciatica has
      increased dramatically during the last decade. However, studies have mainly
      assessed nerve dysfunction rather than pain. Existing methods to study pain
      generally comprise a certain amount of handling and registration of changes in
      sensory thresholds. In the present study we introduce a new way to assess pain
      that focuses on changes in behavior rather than on changes in thresholds.
      METHODS: Forty rats were divided equally into four experimental series: sham
      exposure of the left L4 dorsal root ganglion, exposure of the left L4 dorsal root
      ganglion and incision of the L4-L5 disc, exposure and slight displacement of the
      left L4 dorsal root ganglion, and combination of disc incision and displacement.
      The rats were videotaped the day before surgery and on day 1, 3, 7, 14, and 21
      after surgery. Spontaneous behavior was categorized into 10 behaviors and
      recorded during 20 minutes of observation. RESULTS: Disc incision and
      displacement per se did not induce any behaviors different from that observed in
      the sham-operated group. In the series with the combination of disc incision and
      displacement there was increased focal pain, seen as increased lifting of the
      hind paw on the operated side and increased rotation of the head toward the
      operated side. This pain pattern was most pronounced the day after surgery.
      Fourteen days after surgery there were no detectable differences in behavior
      between this group and the sham group. At day 21 after surgery, however, another
      picture of increased immobility and decreased locomotion was seen in this group,
      possibly indicating more generalized pain. CONCLUSIONS: The study demonstrates
      that it is possible to detect changes in spontaneous behavior after experimental
      disc herniation. However, such changes may only be seen if disc incision and
      slight mechanical deformation are combined. This is in agreement with previous
      clinical and experimental observations. The present model allows for convenient
      assessment of pain in a way that focuses on spontaneous behavior rather than
      changes in pain thresholds and that reduces the interference of the researcher
      and environment on the outcome of the assessment.

PMID- 12065981
TI  - Osteogenic protein-1 enhances matrix replenishment by intervertebral disc cells
      previously exposed to interleukin-1.
AB  - STUDY DESIGN: A study of the mechanisms involved in matrix repair by
      intervertebral disc cells cultured in alginate gel was performed. OBJECTIVES: To
      determine the effects of osteogenic protein-1 on the extracellular matrix of
      intervertebral disc cells previously exposed to interleukin-1, which is an in
      vitro model for degraded extracellular matrix. SUMMARY OF BACKGROUND DATA: Disc
      degeneration is accompanied by a decrease in the content of negatively charged
      proteoglycans in the matrix. No previous attempt has been made to repair the
      degraded matrix of the disc. METHODS: Nucleus pulposus and anulus fibrosus cells
      were isolated from the lumbar discs of New Zealand white rabbits and were
      separately encapsulated in alginate beads. The alginate beads were cultured with
      or without osteogenic protein-1 after previous exposure to interleukin-1alpha in
      the presence of 10% fetal bovine serum. The total contents of proteoglycan,
      collagen, and DNA in the alginate beads were measured. The rate of proteoglycan
      synthesis by the encapsulated cells was also determined. RESULTS: Treatment with
      interleukin-1alpha resulted in a significant decrease in proteoglycan and
      collagen contents in the matrix formed by both the nucleus pulposus and anulus
      fibrosus. However, subsequent treatment with osteogenic protein-1 led in both
      cases to rapid recovery of proteoglycans and collagens, whose contents returned
      to the levels seen in cells not previously exposed to interleukin-1alpha. By the
      end of the culture period (day 21), those values reached levels higher than those
      found in beads containing cells never exposed to interleukin-1alpha. Further, the
      rate of proteoglycan synthesis by both cell types in beads treated with
      osteogenic protein-1 after previous exposure to interleukin-1alpha was
      significantly higher than in beads whose cells were not treated with osteogenic
      protein-1 after previous exposure to interleukin-1alpha. CONCLUSION: Disc cells
      that have been previously exposed to interleukin-1alpha have lost none of their
      potential to upregulate proteoglycan synthesis in response to stimulation with
      osteogenic protein-1. On stimulation with osteogenic protein-1, these disc cells
      not only replenished the matrix with proteoglycans that had been lost during
      interleukin-1alpha treatment but proceeded to reform a matrix that was richer in
      these resilient molecules than that formed by disc cells never exposed to
      interleukin-1alpha.

PMID- 12065982
TI  - Point of view.

PMID- 12065983
TI  - Lower torso muscle activation patterns for high-magnitude static exertions:
      gender differences and the effects of twisting.
AB  - STUDY DESIGN: Surface electromyographic signals were collected from 14 lower
      torso muscles while participants resisted high-magnitude static trunk moments
      applied in a variety of directions. OBJECTIVES: To obtain a description of muscle
      activations in response to large moment magnitudes and axial twisting, including
      levels of agonistic and antagonistic muscle cocontraction. To assess differences
      in lower torso muscle activation patterns associated with gender and trial
      repetition. SUMMARY OF BACKGROUND DATA: Back pain is associated with mechanical
      loads in the back. Biomechanical modeling of these loads is facilitated by
      knowledge of typical muscle activation patterns. Previous efforts in obtaining
      such data have often limited their scope to low-magnitude exertions or relatively
      simple scenarios. METHODS: Eight male and eight female participants, matched by
      height and mass, performed static exertions in an apparatus that immobilized
      their lower body while the activation levels of seven bilateral torso muscles
      were measured using surface electromyography. Activation patterns were analyzed
      to assess differences resulting from a variety of factors. RESULTS: No
      significant differences in activation patterns were found between genders or
      repetitions, but moment magnitude and direction elicited substantial differential
      responses. Good repeatability was found between trial repetitions, as indicated
      by intraclass correlation coefficients (>0.65). Significant synergistic muscle
      coactivation, large intersubject variability (mean coefficient of variation
      82.2%), and consistent levels of antagonism ranging from 10% to 30% maximum
      voluntary exertions were observed. CONCLUSIONS: Individuals of different genders,
      but similar anthropometry, have comparable muscular reactions to complex torso
      loads, suggesting similar motor control strategies. Future spine models should
      consider that the variability in muscle recruitment patterns is larger between
      subjects than within subjects. High-magnitude exertions, especially those with
      moment loads in more than one plane, require most muscles to be active (>5%) and
      moderate levels of antagonism.

PMID- 12065984
TI  - Evaluation of posterior long fusion versus conservative treatment for the
      progressive rheumatoid cervical spine.
AB  - STUDY DESIGN: Results of the posterior long fusion performed for the progressive
      cervical lesions of rheumatoid arthritis were compared with the outcomes of those
      who did not undergo surgical treatment. OBJECTIVE: To provide a clue as to
      whether posterior long fusion improves or maintains the impaired daily life
      activity of the patients with rheumatoid arthritis with progressive, mutilating
      type joint involvements. SUMMARY OF BACKGROUND DATA: To provide optimal
      treatments for the cervical lesions of patients with rheumatoid arthritis, the
      natural courses of cervical lesions should be taken into account. In the authors'
      preliminary study they have retrospectively investigated natural courses of
      cervical rheumatoid arthritis lesions and have found that the seropositive
      patients with rheumatoid arthritis with mutilating-type joint involvement are at
      a high risk of deteriorating the cervical lesion once their cervical spine
      becomes affected. METHODS: In the present study 17 seropositive patients with
      rheumatoid arthritis with mutilating-type joint involvements were studied. Eleven
      patients underwent surgical treatments (operated group), whereas six patients did
      not (nonoperated group). All of the operated patients underwent occipitocervical
      or occipitocervicothoracic fusion supplemented by the Luque's sublaminar wiring
      and preoperative and postoperative usage of halo-jacket. RESULTS: The six
      patients of the nonoperated group worsened the activities of daily living score
      and resulted in either complete bedridden or in death by the time point of final
      follow-up. In contrast, all of the 11 operated patients either improved or
      maintained the activities of daily living score: those operated because of
      neurologic compromise due to myelopathy improved at least one class in the
      activities of daily living score, and those operated because of severe
      occipitocervical pain maintained the activities of daily living with relief of
      pain. CONCLUSION: The present study suggests that posterior long fusion may
      achieve an improvement of activities of daily living, at least, for a certain
      time period. However, the newly emerging lesions adjacent to the fused segments,
      which may result from the increased mechanical loads, may finally lead to the
      impairment of activities of daily living.

PMID- 12065985
TI  - Prospective evaluation of trunk range of motion in adolescents with idiopathic
      scoliosis undergoing spinal fusion surgery.
AB  - STUDY DESIGN: Prospective evaluation of spinal range of motion in patients with
      adolescent idiopathic scoliosis undergoing a spinal fusion. OBJECTIVE: Evaluate
      changes in triplanar spine range of motion following spinal fusion. SUMMARY AND
      BACKGROUND DATA: Preoperative and postoperative radiographs have been the major
      form of outcome analysis of adolescent idiopathic scoliosis fusions. Although the
      radiographs document static positions of the skeletal system, they do not
      document dynamic changes. METHODS: Thirty patients with adolescent idiopathic
      scoliosis undergoing an instrumented spinal fusion underwent triplanar range of
      motion tests before surgery and at 12 and 24 months after surgery. Videography
      with reflective surface markers was used to capture the motions. A fused region,
      unfused regions above and below the fusion, and a global spinal measure were used
      to assess changes. RESULTS: Results indicated a loss of motion in the coronal and
      sagittal planes for the fused and unfused spinal regions and a loss of motion in
      the coronal, sagittal, and transverse planes for the global measurements. Results
      also indicated preoperative and continued postoperative right and left lateral
      flexion asymmetries. No significant correlations were found between the total
      fused levels and changes in range of motion. No significant correlations were
      found between the lowest instrumented vertebra and changes in range of motion.
      CONCLUSIONS: Whereas range of motion was reduced in the fused regions of the
      spine, it was also reduced in unfused regions. The lack of compensatory increase
      in motion at unfused regions contradicts current theory and suggests early
      postoperative range of motion therapy to facilitate motion in unfused regions.

PMID- 12065986
TI  - Activation of back muscles during voluntary abduction of the contralateral arm in
      humans.
AB  - STUDY DESIGN: Motor-evoked responses to transcranial magnetic stimulation of the
      motor cortex were recorded from erector spinae and deltoid muscles while the arm
      was abducted voluntarily in 10 normal subjects. OBJECTIVE: To understand the
      neuronal substrate for the activation of the contralateral erector spinae muscle
      when the opposite arm is abducted. BACKGROUND DATA: When a standing individual
      abducts an arm, the center of gravity is altered; to avoid falling, trunk muscles
      become activated on the contralateral side. METHODS: Surface EMG activity was
      recorded from the right deltoid and left and right erector spinae muscles.
      Subjects maintained abduction of their right arm to 90 degrees at five different
      levels of isometric force in standing and lying postures. Transcranial magnetic
      stimulation was delivered to the motor cortex, producing motor-evoked responses
      in the three muscles during arm abduction and while relaxed. RESULTS: EMG
      activity in the left erector spinae increased with the force of right arm
      abduction in both postures. EMG levels in right erector spinae showed no
      consistent change with right arm abduction force. As arm abduction force was
      increased, motor-evoked responses were facilitated in deltoid and the left
      erector spinae but not the right erector spinae in both postures. The pattern of
      motor-evoked potential facilitation with arm abduction force tended to plateau
      between 50% and 70% maximum voluntary contraction in the deltoid, whereas it
      continued to climb more linearly in the left erector spinae. CONCLUSIONS:
      Facilitation of erector spinae with arm abduction remains evident in the lying
      posture when spinal postural stabilization mechanisms are presumably reduced.
      Similar facilitation profiles have been seen previously with changing voluntary
      activation of erector spinae in a trunk extension task, supporting the notion
      that during arm abduction the drive to the contralateral erector spinae has a
      corticospinal origin.

PMID- 12065987
TI  - Design of the Spine Patient outcomes Research Trial (SPORT).
AB  - SUMMARY OF BACKGROUND DATA: The Spine Patient Outcomes Research Trial (SPORT) was
      designed to assess the relative efficacy and cost-effectiveness of surgical and
      nonsurgical approaches to the treatment of common conditions associated with low
      back and leg pain. OBJECTIVES: To describe the rationale and design of the SPORT
      project and to discuss its strengths and limitations. STUDY DESIGN: Descriptive.
      METHODS: First, the authors explain the rationale for embarking on SPORT, i.e.,
      deficiencies in the existing scientific knowledge base for treatment of these
      conditions. Second, the authors describe the design of SPORT, including topics
      such as specific aims, participating sites, study population, recruitment and
      enrollment, study interventions, follow-up, outcomes, statistical analysis, and
      study governance and organization. Finally, issues that complicate the
      performance of randomized trials in surgery as they relate to the design and
      conduct of SPORT are discussed. RESULTS: The SPORT project is being conducted at
      11 clinical centers around the United States. It involves the simultaneous
      conduct of three multicenter, randomized, controlled clinical trials. The study
      includes patients with the three most common diagnoses for which spine surgery is
      performed: intervertebral disc herniation, spinal stenosis, and degenerative
      spondylolisthesis, and it compares the most commonly used standard surgical and
      nonsurgical treatments for patients with these diagnoses. By the end of
      enrollment the authors anticipate a total of 500 patients with intervertebral
      disc herniation, 370 patients with spinal stenosis, and 300 patients with
      degenerative spondylolisthesis in the randomized trials. Patients who meet the
      eligibility criteria but decline to be randomized are invited to participate in
      an observational cohort study. Patients are being followed for a minimum of 24
      months with visits scheduled at 6 weeks and at 3, 6, 12, and 24 months.
      CONCLUSIONS: The results of this study will provide high-quality scientific
      evidence to aid clinical decision-making and improve treatment outcomes for these
      common, costly, and, in some instances, debilitating conditions.

PMID- 12065988
TI  - Editorial.

PMID- 12065990
TI  - Letters.

PMID- 12065989
TI  - Artificial nucleus replacement: clinical experience.
AB  - The prosthetic disc nucleus is designed to help treat patients suffering from
      degenerative disc disease. The device consists of a hydrogel core that is encased
      in a polyethylene jacket and is intended to restore disc height while permitting
      normal range of motion. Clinical trials for the prosthetic disc nucleus were
      first conducted in 1996, and the device was found to be effective in most of the
      patients that were implanted. Additional trials in 1997-1998 were less
      successful, with 38% of patients requiring revision surgery because of device
      migration. Subsequent changes were made to device shapes and to the surgical
      protocol to facilitate implantation, thereby eliminating the high device
      migration rates. Following these modifications, the success rate for the device
      has improved significantly. Clinical data show excellent results with marked
      improvements in Oswestry and Prolo scores. Overall, disc height measurements have
      been well maintained within normal physiologic ranges. The prosthetic disc
      nucleus device is currently undergoing clinical trials in Canada, and an IDE
      application to the Food and Drug Administration was expected in the fall, 2001.

PMID- 12065991
TI  - Letters.

PMID- 12065992
TI  - Congenital anteroposterior spinal dissociation in Larsen's Syndrome: report on
      two operated cases with long-term follow-up.
AB  - STUDY DESIGN: The outcome of two patients with Larsen's syndrome after spinal
      surgery was evaluated after follow-up for 9 and 16 years. OBJECTIVE: To report on
      a new phenomenon of anteroposterior dissociation of the vertebrae in Larsen's
      syndrome. To demonstrate that it can be visualized before surgery with imaging
      and also seen intraoperatively. To show that the neurologic recovery after
      surgery is sustained and to review the technical reasons for the difficulties in
      achieving a surgical fusion. The critical role of CT scanning will be
      illustrated. SUMMARY OF BACKGROUND DATA: The results of preoperative and
      postoperative radiologic investigations and intraoperative findings are presented
      to support this new phenomenon. METHODS: Two patients underwent multiple spinal
      surgeries because of a deteriorating myelopathic clinical status.
      Intraoperatively, anteroposterior dissociation was documented in both patients.
      There was great difficulty in obtaining a surgical fusion, and an unusually long
      circumferential fusion was eventually necessary to obtain stability. Prolonged
      halo-vest immobilization was essential. RESULTS: Neurologic recovery was
      sustained over time, and the spinal deformity did not deteriorate. CONCLUSION:
      Awareness of this phenomenon is essential to the management of spinal deformities
      in Larsen's syndrome when presenting with myelopathy. Special features in the
      radiologic workup should be sought after so as to plan staged surgical
      procedures. Conventional principles of planning of fusion levels are inadequate.
      Early treatment is advocated, as the neurologic compromise is reversible.

PMID- 12065993
TI  - Thoracic paravertebral leiomyosarcoma: rare but it does occur.
AB  - STUDY DESIGN: Marginal resection of a paraspinal tumor in the thoracic vertebra
      was performed. OBJECTIVE: To document a very rare pathology for a paraspinal
      tumor. SUMMARY OF BACKGROUND DATA: Primary leiomyosarcoma of the spine or
      paravertebral space is extremely rare. A case of a patient who was operated on
      for a mass in the spinal canal and whose pathology was reported to be
      leiomyosarcoma is presented. METHODS: Marginal resection of the paravertebral
      mass was performed. RESULTS: The pathology of the tumor was reported as
      leiomyosarcoma. CONCLUSION: Leiomyosarcomas may develop at any site where smooth
      muscle cells are present. However, primary leiomyosarcoma of the spine or
      paravertebral space is extremely rare. Leiomyosarcoma, although rare, should be
      kept in mind as one of the possible diagnoses when a patient with a paraspinal
      tumor is presented.

PMID- 12065994
TI  - Desmoid tumor of the spinal canal causing scoliosis and paralysis.
AB  - STUDY DESIGN: This report describes a case of successful surgical excision of an
      intrathoracic paraspinal desmoid tumor with an intraspinous extension causing
      scoliosis and paralysis in a 12-year-old girl. OBJECTIVES: The purpose of this
      report is to illustrate the potential spectrum of disease of a desmoid tumor and
      to make physicians aware of the rare possibility of an intraspinal extension of a
      paraspinal desmoid tumor. SUMMARY OF BACKGROUND DATA: Surgical excision of
      desmoid tumors in the pediatric population is the standard of care for initial
      treatment. There have been no clinical reports in the spine literature of a
      desmoid tumor causing scoliosis or of a desmoid tumor with an intraspinous
      extension causing paralysis. METHODS: The tumor was decompressed from a posterior
      approach followed by an anterior resection and an anterior spinal fusion. Two
      weeks later a posterior spinal fusion was performed to correct the spinal
      deformity. The patient also received radiation therapy after surgery for 5 weeks.
      RESULTS: The patient tolerated the procedure well, has been free of recurrence
      for 9 years, and is currently doing well. CONCLUSION: This case report should
      help expand the understanding of the spectrum of this uncommon tumor.

PMID- 12065995
TI  - Myelopathy caused by ossification of ligamentum flavum.
AB  - STUDY DESIGN: Retrospective study of seven cases of ossification of ligamentum
      flavum from two urban hospitals in a Chinese population. OBJECTIVES: To inspect
      the epidemiology, clinical presentation, pathology, and treatment outcome in
      these Chinese patients with ossification of ligamentum flavum. SUMMARY OF
      BACKGROUND DATA: Ossification of ligamentum flavum involving the lower thoracic
      region is relatively common in the Japanese population. It is usually presented
      with myelopathy of progressive nature. MATERIALS AND METHODS: Five patients were
      male and two were female. The mean age was 52 years (range 41-73 years).
      Diagnosis was made by CT scan, MRI, and subsequent histology. Six patients have
      been treated by laminectomy and one by laminoplasty. The average follow-up
      duration is 34 months (range 26-44 months). The outcome is evaluated by Japanese
      Orthopaedics Association (JOA) score. RESULTS: The average time of presentation
      from the onset of symptoms was 9 months (range 3-12 months). Most of the patients
      presented with lower limb numbness and gait disturbance. One case was presented
      after a minor trauma. Mean JOA score was 4.8 (range 2-7, of 11). The lower
      thoracic level was the most frequently involved region. One case was associated
      with ossification of the posterior longitudinal ligament. Two patients had
      transient postoperative neurologic deterioration, which improved subsequently.
      Mean percentage of recovery after surgery in terms of JOA score is 65% (25-100%),
      with a mean final JOA score of 7.8. CONCLUSION: Ossification of ligamentum flavum
      is an uncommon cause of myelopathy in the Chinese population. It can present
      acutely after minor trauma. Posterior decompression, especially with en bloc
      dissection of laminae, gives satisfactory results.

PMID- 12065996
TI  - Myolysis of the erector spinae muscles as the cause of scoliosis in osteoid
      osteoma of the spine.
AB  - STUDY DESIGN: A case of an osteoid osteoma at the lower thoracic spine with
      scoliosis is reported. OBJECTIVES: To suggest that myolysis of the erector spinae
      muscles reflected by signal abnormalities on magnetic resonance images causes
      back pain, protective muscle contraction, and scoliosis. SUMMARY OF BACKGROUND
      DATA: Osteoid osteomas of the spine are frequently accompanied by scoliosis. The
      proposed mechanism of the scoliosis has been explained as a postural adaptation
      of the spine through predominant muscle spasm on the concave side. METHODS: The
      history of the patient and radiologic, magnetic resonance imaging, and histologic
      findings of the peritumoral area were reviewed. RESULTS: Magnetic resonance
      images showed signal abnormalities on muscles surrounding the tumor, and use of
      gadopentetate dimeglumine resulted in an enhancement. The microscopic examination
      of the erector spinae muscles that demonstrated high intensities on T2-weighted
      images showed derangement or destruction of the muscle fibers and replacement of
      the muscle fibers with fat tissue and infiltrating inflammatory cells.
      CONCLUSION: These findings were interpreted as those of myolysis. The suggested
      mechanism of the induction of scoliosis by the present osteoid osteoma is that
      the unaffected iliocostalis and quadratus lumborum muscles on the tumor side
      predominantly contracted over those on the opposite side to decrease the tension
      of the erector spinae muscles involved in myolysis, thereby producing a
      functional scoliosis.

PMID- 12065997
TI  - A comparison of pediatric emergency medicine and general emergency medicine
      physicians' practice patterns: results from the Future of Pediatric Education II
      Survey of Sections Project.
AB  - BACKGROUND: This survey was conducted to obtain information about career and
      practice issues facing pediatric emergency medicine (PEM) physicians and general
      emergency medicine (GEM) physicians. We hypothesized that PEM physicians work
      fewer clinical hours and perform more teaching and research in their positions
      than GEM physicians. METHODS: Two surveys sponsored by the Future of Pediatric
      Education II Project were sent to 1545 emergency physicians identified by the
      American Board of Pediatrics, the American Academy of Pediatrics, and the
      American College of Emergency Physicians between October 1997 and February 1998.
      Data on demographics, job description, recent job changes, and career
      expectations were obtained and analyzed using Student t test or Welch analysis of
      variance for continuous variables and chi2 for categorical data. P values less
      than 0.05 were considered significant. Comparisons between PEM and GEM physicians
      were adjusted using analysis of covariance to control for the effect of medical
      school affiliation. RESULTS: Effective response rate was 934 (64%) of 1451. A
      total of 705 (75%) respondents identified themselves as a PEM physician, and 229
      (25%) identified as a GEM physician. PEM physicians were younger (41.0 y vs 45.1
      y) and more likely to be women (44% vs 15%, P < 0.0001 for both). Children
      younger than 18 years made up 80.9% and 28.6% of patients seen by PEM and GEM
      physicians, respectively (P < 0.001). Seventy-nine percent of PEM physicians and
      42% of GEM physicians held an academic appointment (P < 0.0001). No differences
      were found for full-time equivalents per physician group (9.7 vs 9.1) or clinical
      hours spent in the emergency department (ED) (31.5 vs 32.7) when means were
      adjusted for academic appointment. During ED clinical activities, PEM physicians
      reported more time spent supervising trainees (34% vs 16%, P < 0.0001), and GEM
      physicians reported more time spent in direct patient care (77% vs 57%, P <
      0.0001). Total clinical hours worked per week were greater for GEM physicians
      (37.9 vs 35.3, P < 0.05). PEM physicians spent more time than GEM physicians
      teaching (12% vs 8%, P < 0.005) and conducting clinical research (5% vs 2%, P <
      0.0003). Of PEM and GEM physicians combined, 26% reported a job change in the
      past 3 years. Extended reduction of ED clinical duties occurred most commonly
      because of child care issues and was reported more commonly by women than men
      (53% vs 6%, P < 0.0001) irrespective of PEM or GEM practice. The likelihood of
      leaving emergency medicine practice within 5 years increased with age for both
      groups: 10% of PEM and GEM physicians under 40 years old anticipated leaving
      practice versus 30% of those older than 50 years (P < 0.0001). PEM physicians
      were more likely than GEM physicians to predict an increased need for additional
      pediatric subspecialists in general (60% vs 26%, P < 0.001) and for pediatric
      subspecialists in their discipline (54% vs 17%, P < 0.001). PEM subspecialists
      were twice as likely as GEM specialists to perceive competition in their
      subspecialty (60% vs 31%, P < 0.001). CONCLUSIONS: According to our sample, GEM
      and PEM physicians worked the same number of clinical hours in the ED but
      reported significant differences in how those hours are spent. Job changes and
      extended leaves were common in both groups. These results suggest that PEM and
      GEM physicians face similar vocational challenges, especially in the areas of
      balancing of family time, clinical hours, and academic productivity. These data
      also have important implications for workforce projection for the PEM physician
      supply, given the current estimated attrition rate, frequency of leave from
      clinical duties, and projection for increased need for PEM physicians in the
      future.

PMID- 12065998
TI  - Parent visual analogue scale ratings of children's pain do not reliably reflect
      pain reported by child.
AB  - OBJECTIVES: To determine whether parent and child visual analogue scale (VAS)
      scores for the pain associated with acute conditions in the child agree
      sufficiently for these methods of measurement to be considered interchangeable in
      pain and analgesia research. DESIGN: This was a prospective, two-group, repeated
      measures, blinded study in an urban pediatric emergency department. Children aged
      8 to 15 years seeking treatment for painful conditions and the parents of these
      children were asked to rate the child's pain independently using a VAS on as many
      as four occasions at 20-minute intervals. Both participants were blinded to their
      previous rating and the rating of the other participant. The main outcome measure
      was the correlation of child and parent VAS pain scores by Pearson correlation
      and bias plot (Bland-Altman) analysis of agreement between tests. RESULTS:
      Seventy-eight child-parent sets participated, yielding 289 VAS pain score
      comparison pairs for evaluation. The correlation between child and parent VAS
      pain scores was 0.63 (95% CI, 0.56-0.70). Bias plot analysis revealed a bias of
      5% and 95% limits of agreement from -38 to +47 mm. The degree of difference
      between child and parent scores was variable, but there was an increasing
      tendency for parents to underestimate the child's pain when the child recorded
      VAS pain scores at the higher end of the scale. CONCLUSIONS: Parents' VAS score
      ratings of their children's pain correlate only moderately with the children's
      VAS pain scores and show poor levels of agreement. The difference between the
      measures is variable and appears to be more marked when the child reports a
      higher VAS score. This research raises doubt about whether parental rating of a
      child's pain is an appropriate surrogate marker in pediatric pain and analgesia
      research.

PMID- 12065999
TI  - Current use and perceived utility of ultrasound for evaluation of pediatric
      compared with adult trauma patients.
AB  - OBJECTIVE: The objective of this study was to evaluate the current use and
      perceived utility of ultrasound in the assessment of pediatric compared with
      adult trauma patients. METHODS: A questionnaire was developed and mailed to 72
      pediatric emergency physicians, 120 general emergency physicians, and 117 trauma
      attendings at 240 institutions. RESULTS: Of 309 surveys, 234 (75%) were
      completed. Ultrasound was available to 169 of 234 (72%) of the physicians, and
      122 of 169 (72%) were performing the Focused Assessment by Sonography for Trauma
      examination to evaluate trauma patients. Seventy-three percent (110/150) of
      general emergency and trauma surgeons reported that ultrasound was available
      equally with or more readily than computed tomography (CT) scan. Only 26% (5/19)
      of pediatric emergency attendings considered ultrasound equally available with CT
      scan, and none considered it more readily available than CT scan. Ninety-two
      percent (137/149) of general emergency and trauma attendings responding to the
      question about utility considered ultrasound somewhat useful to extremely useful
      for assessing adult trauma patients, and 77% considered it useful for pediatric
      patients. Only 57% (12/21) of pediatric emergency attendings responding to the
      same question perceived ultrasound as useful for pediatric trauma evaluations.
      CONCLUSIONS: We conclude that ultrasound for the assessment of trauma patients is
      widely used by general emergency physicians and trauma surgeons, whereas
      pediatric emergency physicians report less use and perceived utility.

PMID- 12066000
TI  - Does the pediatric advanced life support course improve knowledge of pediatric
      resuscitation?
AB  - OBJECTIVE: To determine whether the pediatric advanced life support (PALS) course
      contributes to the knowledge required by health care providers for pediatric
      resuscitation and whether differences in achievement exist between professional
      groups. METHODS: Physicians, nurses, and paramedics from across Israel who
      registered for PALS were administered a standardized test both before and on
      completion of the course. Pretest and posttest results were compared by
      statistical analysis. A score of 80 or higher was considered a passing grade.
      RESULTS: Paired pretest and posttest results were available for 370 participants
      (72.5%): 128 physicians, 158 nurses, and 84 paramedics. The percentage of
      participants who passed the course was 83.5% for the entire cohort, 85.9% for
      physicians, 78.5% for nurses, and 89.3% for paramedics. Physicians and paramedics
      had higher pretest and posttest scores than nurses. There was a significant
      improvement in mean posttest scores compared with pretest scores for the entire
      group (86.6 +/- 9.8 vs 78.0 +/- 12.7, P < 0.001) and when results were stratified
      by profession. A significantly greater proportion of participants passed the
      posttest than the pretest both for the entire cohort (83.5% vs 61.9%, P < 0.0001)
      and by profession. CONCLUSIONS: The pediatric advanced life support course
      significantly increases immediate short-term knowledge of pediatric resuscitation
      for all professional groups. This finding supports the use of PALS as an
      educational tool. Further studies are required to determine the effect of PALS on
      actual performance and outcome of resuscitation.

PMID- 12066002
TI  - Acute, unintentional pediatric brodifacoum ingestions.
AB  - BACKGROUND: Brodifacoum is the major rodenticide used in the United States today.
      It is similar to warfarin but has more potent and prolonged effects. Large
      overdoses and chronic intoxication have been associated with significant
      coagulopathies and death. Currently, the management of acute unintentional
      ingestions by young children is controversial. METHODS: American Association of
      Poison Control Centers (AAPCC) data from 1993 to 1996 were retrospectively
      searched for acute, unintentional brodifacoum exposures without coingestions
      followed-up to a known outcome in children aged 6 years and younger. The cases
      were analyzed by management site, symptoms, therapy, and outcome. Cases coded as
      having clinical or laboratory evidence of coagulopathy were further evaluated for
      severity. RESULTS: Our study reviewed 10,762 cases that involved single, acute,
      unintentional ingestions of brodifacoum. All of the patients were followed-up to
      a known outcome as defined by AAPCC data collection standards. In this cohort,
      there were no deaths or major effects reported. Although 67 patients reported
      evidence of coagulopathy, no major effects or deaths were reported. Minor and
      moderate effects were reported in 38 and 54 children, respectively. Management
      occurred outside of a healthcare facility in 5404 (50.2 %) cases. Approximately
      half of all the children received some form of gastrointestinal decontamination.
      Decontamination had no effect on the distribution of outcomes. Adverse effects
      from decontamination therapy were reported in 42 patients. CONCLUSION: Acute
      pediatric ingestions of brodifacoum rarely caused clinical effects and were not
      associated with life-threatening symptoms or death in young children. It seems
      reasonable that acute unintentional ingestions of small quantities of brodifacoum
      by young children can be adequately managed with home observation and parent
      education.

PMID- 12066001
TI  - Cosmetic outcome of scalp wound closure with staples in the pediatric emergency
      department: a prospective, randomized trial.
AB  - OBJECTIVE: The purpose of this study is to compare the cosmetic outcome of scalp
      wound closure with staples to traditional skin sutures. METHODS: A prospective,
      randomized trial was conducted using a convenience sample of children (aged 1-16
      y) with simple scalp lacerations admitted to the pediatric emergency department.
      After parental consent was obtained, patients were randomly assigned to either a
      stapling or suturing procedure. A trained attending physician completed the
      procedure following a standard protocol. Based on previously published data, a
      sample size of 18 patients per group was calculated to give 85% power to detect a
      10% difference on a visual analogue scale (VAS) score (two-sided alpha 0.05).
      Initial outcome of wound healing at 7 to 10 days and final cosmetic outcome after
      6 to 18 months were estimated using a VAS. Cosmetic outcome was assessed by a
      physician blinded to the procedure. Data were analyzed using SPSS (Version 8.02;
      SPSS Inc., Chicago, IL). The VAS scores for the two treatment groups were
      compared using the two-tailed Student t test. Analysis of age, race, mode of
      injury, time interval, and size of the wound were performed to estimate the
      strength of the association of VAS score with the treatment, adjusted for the
      covariates. RESULTS: A total of 42 patients were enrolled. Of the 42, 38 (90.5%)
      finished the initial follow-up and 31 of those 38 (81.6%) finished the final
      follow-up. There were no significant demographic differences between groups at
      recruitment and first follow-up. Among those patients who completed the final
      follow-up, 15 underwent stapling, and 16 underwent suturing. There were no
      significant demographic or baseline differences between the groups. Procedure
      time was significantly lower in the stapling group (P = 0.001). Final follow-up
      evaluations were completed in 12 +/- 4 months. The mean VAS scores at first and
      final follow-up were 78.75 +/- 16.16 and 96.31 +/- 8.06 for the suturing group
      and 86.67 +/- 9.76 and 97 +/- 7.02 for the stapling group (P = 0.17). There
      remained no significant difference in the final follow-up VAS score between
      groups when adjusted for covariates. CONCLUSION: Stapling appears to be a fast
      and cosmetically acceptable alternative to suturing for simple scalp lacerations.

PMID- 12066003
TI  - Stroke after penetrating trauma of the oropharynx.

PMID- 12066004
TI  - A 10-year-old girl with shock: role of emergency bedside ultrasound in early
      diagnosis.

PMID- 12066005
TI  - The case of the slandered Halloween cupcake: survival after massive pediatric
      procainamide overdose.

PMID- 12066006
TI  - Retropharyngeal abscess secondary to traumatic injury.

PMID- 12066007
TI  - Septic thromboembolism from unrecognized deep venous thrombosis in a child.

PMID- 12066009
TI  - Acute pediatric lead poisoning: combined whole bowel irrigation, succimer
      therapy, and endoscopic removal of ingested lead pellets.

PMID- 12066008
TI  - Evaluation of a child with pre-existing disabilities after a traumatic event.

PMID- 12066010
TI  - Abuse or not abuse: that is the question.

PMID- 12066011
TI  - An adolescent with flaccid monoplegia.

PMID- 12066012
TI  - Introducing a simple, weight-based, color-coded, medication dosing device.
AB  - OBJECTIVE: To compare the time required to withdraw various pediatric
      resuscitation medications using traditional techniques and the Per-Kilo Doser
      (PKD), a new weight-based dosing device. METHODS: Seven emergency department
      nurses were each videotaped as they withdrew medications for four different
      pediatric resuscitation scenarios. In random order, each nurse performed a total
      of eight timing trials-four with traditional techniques and four with the PKD.
      The videotapes were later reviewed and timed by two reviewers who were unaware of
      the study purpose. The time to drug withdrawal (announcement of medication and
      dose to be withdrawn until the nurse completed medication withdrawal) was
      measured in seconds. Nonparametric and exact techniques were used to determine
      statistical significance. RESULTS: Using traditional techniques, the mean time to
      drug withdrawal was 71.8 seconds; using the PKD, the mean time to drug withdrawal
      was 43.1 seconds. The mean time difference between the PKD and traditional
      techniques was 29.2 seconds (95% CI, 16.7-41.7). CONCLUSION: The PKD decreases
      medication withdrawal time.

PMID- 12066013
TI  - Club drugs, smart drugs, raves, and circuit parties: an overview of the club
      scene.

PMID- 12066014
TI  - Pediatric emergency medicine: legal briefs.

PMID- 12066015
TI  - Pain in the left shoulder after fall.

PMID- 12066016
TI  - Ultrasound applications for the pediatric emergency department: a review of the
      current literature.

PMID- 12066017
TI  - Knowledge and attitude assessment and education of prehospital personnel in child
      abuse and neglect: report of a National Blue Ribbon Panel.

PMID- 12066019
TI  - Making the most of very little.

PMID- 12066018
TI  - A comparison of dog bite injuries in younger and older children treated in a
      pediatric emergency department.
AB  - OBJECTIVE: Dog bites account for a significant number of traumatic injuries in
      the pediatric population that often require medical treatment. Although agent,
      host, and environmental characteristics of dog bites have been well documented,
      no attempt has been made to compare these characteristics by patient age group.
      The purpose of this study is to determine if differences exist in agent, host,
      and environmental characteristics among younger (< or =6 y) and older (>7 y)
      patients treated in a pediatric emergency department (ED) for dog bites. Findings
      from our study could be used to develop age-specific strategies for dog bite
      prevention. THEORETICAL FRAMEWORK: The epidemiologic triad of
      agent/host/environment formed the theoretical framework. METHODS: The study
      setting was the ED at Children's Hospital of Pittsburgh. Patients were enrolled
      between 1999 and 2000 and were identified through a review of ED records (n =
      386) of children sustaining dog bites. Records were abstracted with a researcher
      designed and validated form for agent (eg, breed, number of biting dogs, owner,
      rabies status), host (eg, age, gender, number and location of bites, treatment),
      and environmental (eg, bite month and time, bite location, events leading to the
      bite, ZIP code) characteristics. Data were analyzed using descriptive and
      inferential statistical tests. RESULTS: Children younger than 6 years constituted
      52.8% (n = 204) of the sample. As compared with older children, a higher
      proportion of younger children were bitten by their family dog (chi2 = 27.64, P =
      0.001) whose rabies shots were up to date (chi2 = 12.08, P = 0.034). A higher
      proportion of younger children were bitten on the face (chi2 = 49.54, P = 0.000)
      and were bitten in their own homes (chi2 = 16.075, P = 0.013). IMPLICATIONS FOR
      NURSING PRACTICE: Young children frequently sustain dog bites from their family
      dog in their own homes. Injuries typically involve severe lacerations to the
      face. Prevention strategies for young children include close supervision of child
      dog interactions.

PMID- 12066020
TI  - Delirium in the terminally-ill cancer patient: aetiology, symptoms and
      management.
AB  - Delirium is a frequent and serious clinical problem in the terminally ill cancer
      patient. Multiple dimensions of delirium make definition, measurement, and
      assessment of it challenging in clinical nursing practice. Assessment and
      management of delirium requires knowledge of the diagnostic criteria for it,
      aetiology, signs and symptoms, and nursing interventions. Four delirium
      assessment scales determined to be useful in assessing patients with terminal
      illness are reviewed. The use of a delirium assessment instrument in routine
      nursing assessments would be important for the nurse's early detection of
      delirium so that interventions to reverse the causes of delirium could
      immediately be implemented.

PMID- 12066021
TI  - The role of the palliative care nurse consultant in promoting continuity of end
      of-life care.
AB  - The provision of end-of-life care through a multidisciplinary integrated
      palliative-care approach is dependent on effective communication between
      professional groups and services. We did a qualitative study, using semi
      structured individual and focus group interviews, in Melbourne, Australia. The
      research aim was to explore the experiences and strategies used by palliative
      care nurses to communicate with general practitioners. We found that palliative
      care nurse consultants in acute hospitals not only provided inpatient
      consultation, but also played an important part in facilitating continuity of
      care across healthcare services by improving existing communication strategies
      and establishing further communication networks. However, there were several
      issues that had the potential to disrupt communication, and this article reports
      on the role of the palliative care nurse consultant in addressing these issues.

PMID- 12066022
TI  - The role of aromatherapy massage in reducing anxiety in patients with malignant
      brain tumours.
AB  - Research suggests that aromatherapy massage (AM) is increasingly being used by
      cancer patients, especially in the palliative care setting, although few studies
      have assessed its effectiveness. I wanted to find out whether AM reduces anxiety
      in patients with a primary malignant brain tumour attending their first follow-up
      appointment after radiotherapy. Eight patients were recruited to the study, which
      comprised three methods of data collection: the measurement of physical
      parameters; the completion of Hospital Anxiety and Depression Scales (HADS); and
      semi-structured interviews. The results from HADS did not show any psychological
      benefit from AM. However, there was a statistically significant reduction in all
      four physical parameters, which suggests that AM affects the autonomic nervous
      system, inducing relaxation. This finding was supported by the patients
      themselves, all of whom stated during interview that they felt 'relaxed' after
      AM. Since these patients are faced with limited treatment options and a poor
      prognosis, this intervention appears to be a good way of offering support and
      improving quality of life.

PMID- 12066023
TI  - Palliative care in a Mediterranean culture: a review of services in the Republic
      of Cyprus.
AB  - This article reviews the provision of palliative care services in the Republic of
      Cyprus, highlighting healthcare resources in general and palliative care in
      particular. An interesting feature of palliative care in Cyprus is the extent to
      which community palliative care provision appears to be expanding and developing,
      with hospice care supplementing the work of home care nurses. The role of the
      home care nurse is discussed and the key role played in patient and family
      education highlighted. The article raises some interesting features of the
      relationship between bereavement and culture highlighting the influence that
      medicalization of health has on traditional ways of caring for patients with
      cancer and non-cancer conditions.

PMID- 12066024
TI  - A study of family carers of people with a life-threatening illness 1: the carers'
      needs analysis.
AB  - This study examines the educational and supportive requirements of carers of
      people with a life-threatening illness. Responses would indicate the content and
      format of an educational or supportive programme of material that might then be
      developed. Twenty-four carers known to a Macmillan team in a national health
      service trust in the north of England were targeted for participation and
      quantitative data collected were analysed manually. Qualitative data arising from
      the carer interviews were subjected to a simple content analysis exercise that
      led to the identification of some overarching themes. In both strands of the
      research, similar emergent themes of physical, emotional and social stress were
      identified. Findings suggest that consideration of carers' age, length of caring
      experience and gender may be helpful in understanding their experience of stress
      and in developing support strategies.

PMID- 12066026
TI  - Metastatic bone disease and tumour-induced hypercalcaemia: the role of
      bisphosphonates.
AB  - Tumour-induced hypercalcaemia (TIH) is the most common metabolic disorder
      associated with cancer, and if left untreated is associated with a low survival
      rate. Bisphosphonates are potent inhibitors of bone resorption. They have emerged
      as the standard method of treatment for TIH and a new form of medical therapy for
      bone metastases in addition to current treatments. Newer forms of bisphosphonates
      are 100-1000 times more potent than pamidronate, the current gold standard. One
      of these third generation bisphosphonates, zoledronic acid (Zometa, Novartis
      Pharmaceuticals) has already been shown to provide more effective treatment of
      TIH than pamidronate. Ongoing research is aimed at choosing the optimum route,
      type of bisphosphonate and combination therapy to inhibit the development of bone
      metastases and TIH.

PMID- 12066025
TI  - The importance of funding palliative care education: a look to the future.
AB  - This article outlines the position statement agreed by the Midlands Palliative
      Care Teachers' Professional Forum. Written by a member of the group, it includes
      suggestions from other members and was submitted for publication before the
      recent announcement of funds being available for palliative education for
      district nurses. The article highlights the challenges facing the adequate
      funding of specialist palliative care education and, in particular, for education
      departments within independent hospices. The statement recognizes the sensitive
      nature of subjects that ought to be included in palliative care education.
      Emphasis is placed on the provision of holistic multiprofessional and
      uniprofessional courses dedicated to enhancing the quality of palliative care.
      The article confirms the commitment of palliative care educationalists to this
      end and looks to continued commitment of adequate funding from NHS trusts and
      regions in supporting existing palliative care education and its ongoing
      development in response to clinical need.

PMID- 12066027
TI  - Nursing must not lose the tradition of the lamp.

PMID- 12066028
TI  - Prison health care: is it a crisis waiting to break?

PMID- 12066030
TI  - Wound colonization and infection: the role of topical antimicrobials.
AB  - Infection and bacterial colonization are important factors in compromised wound
      healing, particularly in chronic wounds. The current "best practice" for
      controlling these factors is still unclear. Systemic antibiotics are generally
      accepted as being the preferred choice for treating infection, provided that
      ischaemia does not interfere. However, their widespread systemic and topical use
      is leading to the emergence of resistant bacterial strains such as methicillin
      resistant Staphylococcus aureus. Colonization of wounds presents a double
      problem: possible delayed healing if out of balance with the immune system; and
      as a source for cross-infection. Managing colonization is not yet defined in best
      practice. The judicious use of dressings, notably those containing certain
      antiseptic agents, can be valuable in infection control and in promoting healing.
      This review states the case for taking the antiseptic route as part of the
      concerted approach to local wound management and infection control.

PMID- 12066029
TI  - Health visitor who failed to promote and safeguard clients.

PMID- 12066031
TI  - Why catheterize?: audit findings on the use of urinary catheters.
AB  - Urinary catheters can be associated with complications such as urinary tract
      infection, pain and discomfort. This article reports on an audit of 51 patients
      who had a urinary catheter inserted during their hospital stay. Urinary
      incontinence meant catheterization in 37.5% (n = 27) of cases, with 64.7% (n =
      33) being catheterized by nurses. The study highlighted the need for accurate
      documentation and care planning; 15 patients did not have a plan of care for
      their catheter and only eight patients had a plan for the removal of the
      catheter. Catheterization is the most common cause of hospital-acquired
      infection, and therefore the use of catheters needs careful examination to reduce
      this type of infection. The question is raised whether catheterization is used as
      a convenience for nursing staff or as an essential aspect of care.

PMID- 12066032
TI  - Managing faecal retention and incontinence in neurodisability.
AB  - The large number of patients with faecal retention and/or incontinence in
      continuing care wards and rehabilitation units presents a considerable challenge.
      In order to maintain dignity and minimize the unpleasant odour so commonly
      associated with these wards and units, effective bowel management should be
      planned for individual patients. For an effective bowel management regime a team
      approach should be adopted, involving, where possible, the patient and carer as
      well as all the health professionals administering the care. Two case studies
      illustrate the use of assessment and management of bowel problems in patients
      with severe complex neurodisability. Bowel dysfunction in this patient
      population, in general, is poorly covered in the literature. The present article,
      by relating theory to practice, offers information and guidance for nurses
      working with patients who have bowel-related problems.

PMID- 12066033
TI  - Nutrition and the life cycle 5: nutritional needs of older adults.
AB  - The previous four articles in this series on nutrition and the life cycle
      reviewed the nutritional needs during pregnancy (Vol 9(17): 1133-8), infancy (Vol
      9(21): 2205-16), childhood (Vol 10(1): 26-31) and adulthood (Vol 10(6): 362-9).
      This article, the last in the series, will review the special nutritional needs
      of the older person. Older adults form an increasing proportion of our society,
      and it is important that nurses appreciate their special needs. The article
      concentrates on the health older adult, and reviews what nutritional advice
      nurses should be providing order to help them achieve maximal health.

PMID- 12066035
TI  - Legal aspects of consent 5: how to judge mental capacity.

PMID- 12066034
TI  - Supporting family carers in the UK: overview of issues and challenges.
AB  - Support for family carers is currently a policy priority in both health and
      social care. However, despite the launch of the Carers' National Strategy there
      is a need for further innovation if services are to be optimally effective. This
      article identifies a number of issues and challenges for the future if family
      carers are to receive the type and level of support they need. It highlights the
      need to think more clearly about the intended outcomes of services supporting
      carers and about the range and type of interventions that should be provided if
      such outcomes are to be achieved.

PMID- 12066036
TI  - Clinical efficacy of C-View transparent film wound dressing.
AB  - This article discusses the use of transparent film dressing in wound management.
      It focuses on one particular product, C-View (Maersk Medical), determining its
      efficacy through multiple case study review. C-View was found to be easy to use
      and cost-effective, both as a primary and secondary wound dressing.

PMID- 12066037
TI  - The problems of student supernumerary status.

PMID- 12066038
TI  - Matron is to stage a comeback in nursing.

PMID- 12066039
TI  - Nurses must be ready for clinical negligence.

PMID- 12066040
TI  - A&E nurse who physically and racially abused patients.

PMID- 12066041
TI  - The use of intermittent pneumatic compression in venous ulceration.
AB  - Even with the application of four-layer bandaging, the recommended treatment for
      venous leg ulceration, patients with reduced mobility have delayed ulcer healing.
      Intermittent pneumatic compression (IPC) has an established role in deep vein
      thrombosis prophylaxis and has been shown to influence fibrinolysis, tissue
      oxygenation, oedema and venous return. It has also been suggested, but not yet
      proven, that IPC may improve the healing of venous leg ulcers. An extensive
      review of the literature has demonstrated that the use of this treatment on
      patients with reduced mobility has not been previously studied; yet, analysis of
      difficult-to-heal ulcer patients would indicate that this method of treatment may
      be appropriate and requires further study.

PMID- 12066042
TI  - The new learning disabilities White Paper: did it forget something?

PMID- 12066043
TI  - Assessing pain in people with profound learning disabilities.
AB  - People with profound learning and multiple disabilities are at risk of pain
      because they experience complex and severe health conditions and frequently
      undergo surgical procedures that cause pain. Pain assessment in this client group
      requires a skilled approach, although there is little evidence available to guide
      nursing practice. In the absence of pain assessment measures specifically
      designed for use with people with profound learning disabilities, the nurse will
      need to rely on careful observation and interpretation of the client's
      communicative behaviour, clinical judgement and knowledge of the person during
      assessment. Intuition is also an important attribute and can be a valuable source
      of knowledge when assessing clients who are unable to verbalize their experience
      of pain. These issues, along with implications for nursing practice, are
      explored.

PMID- 12066044
TI  - The challenge of evidence-based practice for learning disabilities.
AB  - There is an ever-increasing pressure on professionals within both health and
      social care settings to demonstrate evidence-based practice. The main aim of this
      article is to consider as problematic the challenge of evidence-based practice
      for both health and social care professionals, with particular reference to those
      working in the field of learning disabilities. The article addresses a number of
      issues, including the nature of evidence, the different types of evidence that
      professionals have at their disposal, and issues of reliability and validity
      concerning the kinds of approaches used to obtain such evidence. The challenges
      of implementing evidence into practice are also discussed in relation to
      ideology, organizational implications, and educational issues.

PMID- 12066045
TI  - Improving the health of older people: what do we do?
AB  - This article, based on a paper given at the International Network for Studies
      Concerning Older Adults conference in Brazil, considers the health of older
      people. It argues that greater efforts must be made both to improve preventive
      healthcare interventions and enhance quality of life. It is suggested that nurses
      have a significant but, as yet, largely unrealized role to play and that action
      is needed if older people are to get maximum benefit from health care.

PMID- 12066046
TI  - Gastric cancer: diagnosis, risk factors, treatment and life issues.
AB  - Gastric cancer is the sixth most common malignancy in the UK. It is responsible
      for over 9000 deaths annually in the UK. Distal gastric cancer has a decreasing
      incidence, but proximal gastric cancer continues to increase. Gastroscopy remains
      the gold standards for accurate diagnosis. Early diagnosis is essential, but
      symptoms and signs are often mistaken for other less serious diseases. Major
      surgery is the only proven treatment, but 5-year survival rates postoperatively
      are only 34%, and many people will continue to suffer side-effects of the
      surgery. Open access gastroscopy and health promotion may be the best chance of
      detecting this disease early enough so that it is treated successfully.

PMID- 12066047
TI  - The resuscitation status of a patient: a constant dilemma.
AB  - Since the first description of closed chest cardiac massage in 1960, healthcare
      has evolved considerably. The modern-day skill and expertise of both doctors and
      nurses in cardiopulmonary resuscitation (CPR) techniques are now supported by an
      advanced medical technology. Indeed, CPR is now perceived as the definitive life
      saving procedure. However, paradoxically, it has also prolonged the process of
      dying and denied many patients a dignified and peaceful death. It has also denied
      the patient's loved ones the opportunity to be present at the time of death. The
      main focus of this article is to explore the current ethical issues in clinical
      practice relating to determining the resuscitation status of patients. Attention
      will also be given to patient advocacy, and the nurse's role in supporting this
      concept.

PMID- 12066048
TI  - Legal aspects of consent 4: duty to inform patients of risks.

PMID- 12066049
TI  - Euthanasia: what is the nursing and medical role?

PMID- 12066050
TI  - The NHS Plan: stifling the patient's voice?

PMID- 12066051
TI  - Quality of life in leg ulcer assessment: patients' coping mechanisms.
AB  - An increase in autonomous practice and the need to evidence professional update
      puts demands on individual nurses to reflect on their knowledge and practice.
      Community nurses have become expert at managing wounds, particularly leg ulcers,
      and using a variety of assessment strategies. However, reflections focused on the
      expert patient and their coping mechanisms may suggest that holistic assessment
      and treatment of these patients requires consideration of additional factors. The
      introduction of quality of life (QoL) tools may provide the rationale for an
      individual patient's nursing care in this specific context. Placing emphasis on
      the social and psychological impact of living with a leg ulcer - from the
      patient's perspective - may direct collaborative assessment and informed decision
      making.

PMID- 12066052
TI  - Managing people on sip feeds in the community.
AB  - Community nurses often have the difficult task of identifying and coordinating
      the care of under-nourished patients in the community. Studies have shown that
      patients who are underweight are likely to visit to their general practitioner
      more often, need more medication and be admitted to hospital. Nutritional sip
      feeds have been shown to clinically benefit underweight patients suffering from
      chronic conditions as well as the older people. Adapting ordinary food to meet
      the patient's nutritional requirements should be considered first, but sip feeds
      provide an additional source of nutrients when this proves insufficient. All
      patients on sip feeds should have a clear aim for this nutritional intervention
      (e.g. the healing of a pressure area) and be monitored regularly.

PMID- 12066053
TI  - Distinguishing chronic obstructive pulmonary disease from asthma.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are the most common
      chronic respiratory diseases in the UK. Good management of both diseases results
      in better symptom control and improved quality of life for the patient, but will
      rely on all members of the primary healthcare team sharing the aims of management
      as well as helping to implement those goals. The two diseases share many clinical
      features and similar drugs can be used to treat them both. However there are
      important clinical differences which help to distinguish them from each other.
      The management of the two diseases differs in drug regimens and in the long-term
      aims of management. This article clarifies the important features that
      distinguish asthma from COPD and which allow patients to receive the best
      specific management.

PMID- 12066054
TI  - Managing chronic obstructive pulmonary disease in primary care.
AB  - Chronic obstructive pulmonary disease (COPD) causes significant morbidity in
      primary care. The main symptoms of COPD are cough and shortness of breath, while
      the main cause of the disease is smoking. It is a treatable condition, and to
      ensure best treatment it needs to be differentiated from asthma. Following the
      publication of guidelines by the British Thoracic Society in 1997, primary care
      has been given a framework for managing this condition. In primary care, COPD is
      best managed in a specific COPD clinic. This allows for staff training (both
      management decisions and techniques of lung infection monitoring), as well as
      presenting the patient with a therapeutic environment conducive to positive
      lifestyle education. This article discusses the setting up and running of a COPD
      clinic in primary care.

PMID- 12066055
TI  - Informed choice in cancer pain: empowering the patient.
AB  - Cancer and palliative care service users can often feel isolated and
      disempowered. (Tower, 1999). Physical changes, medical interventions and pain can
      mean that they no longer feel in control of their bodies or their futures. In
      recognition of this, many health professionals within cancer and palliative care
      have adopted the mantra of 'patient empowerment', but it is not always clear what
      it means for either the patients or the professionals. Empowerment is an
      interactive process that develops and increases power through cooperation,
      sharing and working together (Marquis and Huston, 2000), and it plays a central
      role in health professionals' personal and working lives. A person's ability to
      make decisions and choices demonstrates control of his or her own destiny. This
      article aims to direct health professionals' participation and involvement in
      restoring this ability to patients who have pain related to cancer.

PMID- 12066056
TI  - The changing focus of mental health nursing in east London.
AB  - The focus of care for Community Mental Health Nurses (CMHNs) has been moving
      towards the Severely Mental Ill (SMI) client group over the past ten years.
      Government guidelines and nursing literature indicate that SMI clients have been
      neglected in the past and that CMHNs should now prioritize this client group.
      This paper attempts to define the term SMI and to ascertain whether or not CMHNs
      in three east-London boroughs are prioritizing this client group. The opinions of
      these CMHNs are also given in relation to the specific new education and training
      required to work with this client group. We found that CMHNs were conscious of a
      distinct shift in focus towards SMI clients, but that they often felt
      inadequately trained for this change in focus. Recommendations are made for the
      future training and education of CMHNs to enable them to work with SMI clients
      more effectively.

PMID- 12066057
TI  - A comparison of two hydrocolloid sheet dressings.
AB  - This article examines the clinical application of hydrocolloid dressings as a
      whole. Two thin hydrocolloid sheets - Tegasorb thin and Duoderm extra thin - were
      essayed in the clinical area, and compared for their ease of application and
      removal, conformability, wear time and patient comfort. Both dressings were found
      to be highly acceptable in clinical practice, with advantages and disadvantages
      to each type of dressing. There was a high level of patient acceptability and no
      adverse reactions were noted during this evaluation. Pain reduction was noted by
      patients with superficial pressure sores and trauma wounds that were treated with
      thin hydrocolloid sheets.

PMID- 12066058
TI  - Recording wounds: Polaroid's new medically-designed cameras.
AB  - Wound management is an important and increasingly complex area of nursing
      practice. Community nurses, in particular, spend a considerable amount of time
      assessing, evaluating and managing chronic, non-healing wounds. The rapid rise in
      the number of wound care products, combined with the emphasis on clinical
      governance and risk management, and increases in litigation have meant that
      accurate documentation and record keeping have become an essential part of care
      (UKCC, 1992, 1998). A standardized approach to assessment, classification,
      measurement and evaluation should be adopted to maximize optimal patient
      outcomes. There are a number of techniques for measuring wounds, ranging from
      manual measurement using tracing to computer-based imaging. Photography is a
      simple and quick form of documentation, which provides an accurate and objective
      record of the wound. This article highlights the benefits of using the new
      Polaroid Macro 5 SLR camera in wound documentation.

PMID- 12066059
TI  - Older people deserve better.

PMID- 12066060
TI  - Don't hide your light under a bushel.

PMID- 12066061
TI  - Life after shingles: the management of postherpetic neuralgia.
AB  - Chronic pain may have devastating effects on the physical and psychological well
      being of many patients (Harden, 1999). Most community nurses are in contact with
      a number of patients with chronic pain and will be asked for advice and
      recommendations with regards to its management. Chronic neuropathic pain is a
      complex and sometimes intractable condition that patients will seek help for,
      from either GPs or from the community nursing teams. This article will examine
      one neuropathic pain syndrome - post-herpetic neuralgia - and review the evidence
      base in relation to treatment strategies, in an attempt to support community
      staff in the management of this difficult to treat pain syndrome.

PMID- 12066062
TI  - Community provision for informal live-in carers of stroke patients.
AB  - Stroke is common and disabling. Most stroke patients are cared for at home by
      informal carers. This study of informal carers of stroke patients measured
      service provision and satisfaction with different aspects of community care
      received by these carers. Dissatisfaction was expressed with training and
      information provision for carers, communication between carers and community
      services, speed of response and coordination of community services, and perceived
      support. Problems of information provision were most marked for those patients
      with most disability and/or older carers.

PMID- 12066063
TI  - The RCP's 'Three Key Questions' for asthma: review of practical use.
AB  - Assessment tools are a vital component of chronic disease management. The Royal
      College of Physicians has developed a patient-focused outcome measure for the
      treatment of asthma, the 'Three Key Questions'. However, in a study investigating
      the goals of people with asthma, several issues related to the tool emerged.
      Forty-seven adults of a range of ages and asthma severity but with no significant
      co-morbidity were interviewed. It emerged that the outcome measure may be subject
      to recall bias. Also, symptom reports may be conflated if daytime symptoms also
      occur with activity. 'Interference with activity' is a subjective term the
      interpretation of which varies considerably. Changes in the level of activity
      undertaken may be reported rather than changes in symptom severity. The 'Three
      Key Questions' are not fully patient-centred because they assess the presence of
      symptoms rather than their importance to the individual. The use of the 'Three
      Key Questions' as an outcome measure may not allow valid comparisons to be made
      between settings.

PMID- 12066064
TI  - Community infection control: what is the evidence?
AB  - Evidence-based practice is the conscientious use of current best evidence in
      decision-making about care or the delivery of health services (National Institute
      for Public Health, 1996). Evidence-based health care is one aspect of the quality
      improvement activities of clinical governance as a main component of the
      programme of quality in the NHS (Hek, 2000). Practitioners working in clinical
      areas are therefore being required to deliver care that has been shown to be
      effective. (Playle, 2000).

PMID- 12066065
TI  - Nurses' confidence and pharmacological knowledge: a study.
AB  - The introduction of nurse prescribing will assist the government to deliver its
      agenda of providing patients with faster access to advice and health services.
      This study evaluated the knowledge base, self-rated knowledge and confidence, for
      a prescribing role, in a group of community nurses in Essex. A questionnaire was
      distributed to 183 community nurses recruited using a random, stratified method,
      and 110 nurses returned completed forms. Nurse prescribers in the sample were
      more confident and rated their knowledge more highly when compared with non
      prescribing nurses. However, prescribers' actual medication-related knowledge,
      relative to their high levels of confidence, was not confirmed with performance
      on case scenarios. In responses to the case scenarios, prescribers did not
      perform as well as non-prescribers on all five analysed scenarios. The overall
      assessment of the nurses' response to the OTC case scenarios showed a poor
      performance when compared with prescription cases. There is a need to improve
      community nurses' levels of confidence and their abilities in coping with
      medication-related issues at pre-registration and post-registration level.

PMID- 12066066
TI  - Treating fever in children: paracetamol or ibuprofen?
AB  - Community health practitioners frequently prescribe or advise parents on
      antipyretic medications for children with fevers. This mini-review sets out to
      examine the evidence for the relative effectiveness of two of the most widely
      available and commonly used over-the-counter medicines - paracetamol and
      ibuprofen. A systematic literature search was undertaken to identify all studies
      comparing the effects of the two drugs. The Medline, Embase, Cinahl and RCN
      databases were searched. Eight randomized controlled trials that reported
      temperature differences at time-points between 1 and 6 hours after administration
      were identified. Statistical meta-analysis showed no clear benefit for one drug
      over another 1 hour after administration. However, by 6 hours after
      administration ibuprofen was clearly superior resulting in a mean temperature
      0.58 degrees C lower than paracetamol. Both drugs appeared well tolerated and no
      evidence of difference in short-term adverse effects was observed. Both drugs are
      effective antipyretics but the longer action of ibuprofen may make it preferable
      in some circumstances.

PMID- 12066067
TI  - PEG site infections: a novel use for Actisorb Silver 220.
AB  - Any breach in the integrity of the skin, such as occurs in wounds and incisions,
      and intravascular catheters, can act as a portal for the ingress of
      microorganisms and thereby predispose the patient to infection. The infection, if
      unchecked, can put the patient at risk of bacteraemia. We have reviewed the care
      of percutaneous enterostomal gastrostomy (PEG) sites in our trust hospital and in
      the local community and have implemented practice guidelines to reduce infection
      risks. These include protocols for skin care around PEG sites, and the use of an
      antibacterial dressing - Actisorb Silver 220 - to manage local colonization. The
      preliminary results of this exercise indicate that patient comfort can be
      improved, hypergranulation reduced, and methicillin-resistant Staphylococcus
      aureus colonization and infection eradicated.

PMID- 12066069
TI  - Keeping kids healthy: a school nursing strategy.

PMID- 12066068
TI  - Good intentions will not meet older care needs.

PMID- 12066070
TI  - Clinical teaching by community nurses in the Australian context.
AB  - A study was conducted to explore factors that impact on the clinical teaching
      role of community nurses involved in the education of pre-registration nursing
      students. Respondents were community nurses working in the Western Sydney Area
      Health Service in New South Wales, Australia. A self-report questionnaire was
      developed to collect data. Results indicate that community nurses are interested
      in clinical teaching, that it is an important part of their role and that they
      perceive themselves to be effective clinical teachers, with the majority
      indicating motivation to continue developing their clinical teaching skills.
      Aspects of clinical teaching important to community nurses included facilitating
      the transition of education from theory to practice, sharing expertise, knowledge
      and skills and maintaining high standards of nursing practice. There was little
      support for the view that community nurses experienced difficulty in managing the
      dual teaching and practice role. Approximately a third of participants reported
      that being with a student on a one-to-one basis could be stressful. Strategies to
      assist community nurses in their clinical teaching role were identified.

PMID- 12066071
TI  - Evaluation of an electric bed frame and pressure-reducing mattresses.
AB  - Pressure ulcers remain a challenge to all healthcare professionals. With the
      trend towards caring for ill patients in the community there is a need to ensure
      that equipment used to prevent pressure ulcers in these patients is effective. It
      is not always appropriate to simply use equipment designed for hospital. This
      article describes the evaluation of an electric bed frame and three mattresses
      specifically designed for patients in the community, in either their own homes or
      nursing home/residential care. The location of this research can reduce the
      number of participants recruited. In order to compensate for this, three
      different methods of evaluation were employed - clinical, laboratory and
      anecdotal - which have produced results relevant to both purchasers and users of
      the system tested.

PMID- 12066072
TI  - The role of community-based nurses in health promotion.
AB  - It is the responsibility of all nurses to incorporate health promotional and
      health education activities into their professional roles. Much of the literature
      around this issue relates to the specific role of community-based nurses in the
      primary healthcare team, and identifies their unique position and responsibility
      for pioneering the universal acceptance and adoption of health-promoting
      practice. Community-based nurses are in a good position to commission health
      related activities and integrate them into practice (Department of Health and
      Social Security, 1987; Department of Health, 1992, 1996). On the basis of this,
      one might expect that the results of studies in this area would identify evidence
      of good understanding, adoption, parity and support for such initiative among
      community professionals. However, many studies have identified a state of
      confusion, poor understanding, a lack of parity between professional groups, a
      lack of professional support and training, and haphazard implementation of such
      strategies (Dines, 1994; Russell, 1997). Inconsistency in study findings is
      problematic and tends to present a skewed picture of current practice. It is
      suggested that community-based nurses may benefit from a change in the way they
      view the implementation of health promotional practices, and that policy issues
      related to practice could be further clarified and enforced.

PMID- 12066073
TI  - A community nurse-led project to tackle health inequalities.
AB  - The Government has emphasized the importance of reducing inequalities in health
      and health care by giving those working with deprived communities the opportunity
      to develop new initiatives to address inequalities. Community nurses, although
      laying claim to the wider public and community health agenda, have yet to clarify
      the nature of their contribution in reducing inequalities and demonstrate it in
      practice. This article reports on an evaluation of a community-based nursing
      initiative in a deprived inner-city community. The findings suggest that
      community nurses can play an important role in supporting people to access health
      care more effectively. In addition, by contextualizing health messages and
      initiatives to reflect the local culture, community nurse can make it easier for
      people to participate in health-enhancing activities. It is also suggested that
      some of the theoretical models developed to guide practice in addressing
      community health issues like inequalities need to be more rigorously tested and
      evaluated in practice.

PMID- 12066074
TI  - Communicable disease and infection control: the surveillance contribution.
AB  - In its much-publicized report (2000) the National Audit Office (NAO) has
      emphasized the important part surveillance plays in determining infection rates
      and infection control in general. Community nurses may be forgiven for pointing
      out that this report concentrates on hospitals, however it strongly recommends
      that surveillance be extended out into the community. This is a sensible move as
      studies quoted in the NAO report indicate that 50-70% of surgical wound infection
      occur during the post-discharge period. The boundaries between acute and primary
      care are becoming ever more blurred; increasing numbers of susceptible patients
      are being managed in the community and the number of invasive procedures carried
      out is rising in line with government policy. Action to control infection extends
      beyond the narrow boundaries of health care to involve the whole population, and
      although the idea of extending the surveillance of healthcare related infection
      from hospital to community settings appears to be relatively new, the
      surveillance of infectious diseases that occur in the community is not. It is, in
      effect, a key proactive infection control activity which facilitates targeted and
      effective infection control measures. This article aims to define and explain
      surveillance as it relates to infection control and communicable disease control
      in the community by using examples from history, the current Meningitis C
      vaccination programme and the surveillance of hospital-acquired infection in the
      USA.

PMID- 12066075
TI  - What should be the limits of nurse prescribing?

PMID- 12066077
TI  - Living with a pressure ulcer: a descriptive study of patients' experiences.
AB  - This qualitative study explored the perceptions and feelings of patients with
      pressure ulcers. Five participants who had suffered from pressure ulcers
      extending into the subcutaneous tissue and deep fascia were interviewed. A semi
      structured interview technique was used, in which participants were asked a
      series of open questions based on the reviewed literature and the author's
      clinical experience. Content analysis was used to analyse the interview
      transcripts. The following themes emerged: pain, exudate levels, loss of
      independence, emotional factors, worry about healing, relationships, body image
      and social isolation.

PMID- 12066079
TI  - The management of surgical wounds in a community setting.
AB  - Many patients are now having minor surgical procedures carried out in the
      community and those patients who undergo surgery in hospital are likely to be
      discharged earlier due to increasing pressure on hospital beds. This article
      discusses the management of surgical wounds healing by both primary and secondary
      closure, in the community setting. Understanding the complex process of wound
      healing is essential if nurses are to recognize abnormalities and select
      appropriate treatments for patients. The stages of wound healing will be
      discussed in detail, including the patient's presentation. Factors that influence
      this process within the patient (e.g. age, nutrition, medication and pain) and
      those at the wound bed (e.g. exudate, tissue type and infection) will be
      highlighted. Choosing the correct type of surgical wound dressing for the type of
      wound can contribute to wound healing, patient comfort and the cost-effectiveness
      of treatment. Factors that need to be taken into consideration when choosing a
      dressing will be outlined and suggestions made for the type of dressings that
      would be most appropriate. The importance of accurate and detailed documentation
      will be highlighted as part of this process.

PMID- 12066080
TI  - Use of sugar in the treatment of infected leg ulcers.
AB  - Mrs R is an 84-year-old retired shop-keeper with a 17-year history of recurrent
      leg ulceration. She has received treatment in both primary and secondary care
      settings, including specialist dermatology and vascular clinics. Mrs R has a long
      history of non-compliance to treatment regime, removing bandages and rucking them
      down causing compression injuries that almost resulted in amputation of her right
      leg. On assessment by the author, she had two partial thickness ulcers to each
      leg, signs of venous insufficiency and malnutrition, and swabs cultured positive
      for a range of bacteria. Resistance to topical antimicrobials and allergy to
      systemic antibiotics meant that another solution had to be tried to relieve the
      bacterial load on Mrs R's wounds.

PMID- 12066078
TI  - Management of a paraplegic patient with a full thickness ischial pressure ulcer.
AB  - Betty was a 72-year-old paraplegic patient with a full thickness ischial pressure
      ulcer. After an overview of the care delivered in hospital, this case study will
      focus not on the management of the wound but on the attempts made towards safe
      discharge home of the patient after an initial failed discharge. The diversity of
      problems encountered over a period of 18 months proved extremely challenging for
      all disciplines involved and required the development of close working
      relationships to achieve an eventual successful outcome. On reflection there are
      many aspects of this case that would undoubtedly be now managed differently. I
      had been in post for only a short time when my involvement with the patient began
      and my links with other members of the multidisciplinary team were tenuous.
      However the relationships fostered over this period of time have ensured that
      future cases have been dealt with efficiently and effectively. The case study
      concludes with a happy ending for the patient when successful surgery to repair
      the ulcer was initiated, not by medical or nursing personnel but by the patient
      herself.

PMID- 12066081
TI  - Randomised, comparative study of three primary dressings for the treatment of
      venous ulcers.
AB  - In this article, we describe a randomised trial in which two established primary
      dressings - Comfeel (Coloplast, UK) and Granuflex improved formulation (Convatec,
      UK) - were compared to Cutinova foam (Beiersdorf Medical, UK) in the management
      of venous leg ulcers. Patients that met the study trial criteria were randomised
      to receive one of the three primary dressings. All ulcers were secondarily
      bandaged with Comprilan (Beiersdorf Medical, UK) short-stretch compression. The
      three dressings were compared in terms of their ability to promote ulcer healing
      (closure rate and healing rate) and reduce the prevalence and severity of ulcer
      associated pain, over a 12-week period. The ease with which dressings could be
      used in a busy outpatient clinic setting was also considered. On enrollment,
      groups were well matched in terms of all of the patient and ulcer parameters
      studies. Six patients were withdrawn for reasons unrelated to study dressings or
      trial procedures. Following non-parametric analysis of the study data, the three
      dressings were found to be equally effective at promoting ulcer healing and
      alleviating ulcer-associated pain. Study personnel rated Cutinova Foam as easy,
      if not easier, to use than Comfeel or Granuflex. This study suggests that
      Cutinova Foam is as safe and effective as both Comfeel and Granuflex, in the
      treatment of venous leg ulcers.

PMID- 12066082
TI  - Association between the use of antenatal magnesium sulfate in preterm labor and
      adverse health outcomes in infants.
AB  - OBJECTIVE: The purpose of this study was to determine whether the use of
      antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular
      hemorrhage, periventricular leucomalacia, death, and cerebral palsy). STUDY
      DESIGN: In a controlled trial, we randomized mothers in preterm labor to
      magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord
      blood was collected for the later determination of serum ionized magnesium
      levels. Neonatal cranial ultrasound scans were obtained periodically for the
      diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among
      survivors, the diagnosis of cerebral palsy was made at age 18 months. RESULTS:
      Children with adverse outcomes had higher umbilical cord magnesium levels at
      delivery. In regression models that controlled for confounders, which included
      very low birth weight, magnesium remained a significant risk factor (adjusted
      odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03). CONCLUSION: Contrary to original
      hypotheses, this randomized trial found that the use of antenatal magnesium
      sulfate was associated with worse, not better, perinatal outcome in a dose
      response fashion.

PMID- 12066083
TI  - Subcutaneous stitch closure versus subcutaneous drain to prevent wound disruption
      after cesarean delivery: a randomized clinical trial.
AB  - OBJECTIVE: The purpose of this study was to compare a subcutaneous stitch closure
      and subcutaneous drain placement for the risk of wound disruption after cesarean
      delivery. STUDY DESIGN: This was a prospective randomized clinical trial that
      evaluated subcutaneous stitch closure, placement of a subcutaneous drain, or no
      closure for subsequent wound disruption risk in women with subcutaneous depth at
      >or=2 cm. RESULTS: The maternal demographics and intrapartum risk factors for
      postoperative wound disruptions were similar among the 964 study subjects, who
      were divided into 3 groups. Wound disruptions that required opening of the wound,
      irrigation, debridement, packing, and/or secondary delayed closure occurred in
      9.7% of the women with no closure, 10.4% of the women in the stitch closure
      group, and 10.3% of the women in the closed drain group (P =.834). CONCLUSION:
      There appears to be no difference in the subsequent risk of wound complications
      when no closure of the subcutaneous tissue layers occurs versus suture closure or
      a closed drainage system.

PMID- 12066085
TI  - Five-year experience with midtrimester amniocentesis performed by a single group
      of obstetricians-gynecologists at a community hospital.
AB  - OBJECTIVE: The purpose of this study was to determine the pregnancy loss rate
      after genetic amniocentesis that was performed by general obstetrician
      gynecologists in a community hospital. STUDY DESIGN: Medical records and billing
      information were used to identify all genetic amniocenteses that had been
      performed by a group of general obstetricians-gynecologists from 1996 through
      2000. Maternal charts were reviewed for data that were pertinent to the risk of
      fetal loss: maternal age, parity, ethnicity, procedure indication, gestational
      age at procedure, karyotype results, physician operator, gestational age at
      delivery, and live birth/stillbirth. RESULTS: During this 5-year time period, 370
      procedures were performed by this physician group. Completed delivery outcomes
      were available on 369 of 370 patients (99.7%). Three patients underwent pregnancy
      termination. Data were analyzed on the remaining 366 patients. There was 1
      pregnancy loss (amniocentesis at 17 weeks with vaginal bleeding at 21 week and
      preterm delivery at 24 weeks). There was 1 other procedure-related complication:
      membrane rupture 7 days after the procedure, with spontaneous resealing of the
      membranes after prolonged bedrest. CONCLUSION: Over a 5-year period, pregnancy
      loss after midtrimester amniocentesis performed by general obstetrician
      gynecologists was 1 in 366 procedures.

PMID- 12066084
TI  - Cervical ripening and induction of labor with misoprostol, dinoprostone gel, and
      a Foley catheter: a randomized trial of 3 techniques.
AB  - OBJECTIVE: The purpose of this study was to compare the efficacy of 3 different
      techniques of cervical ripening and induction. STUDY DESIGN: Patients who
      required cervical ripening and induction were randomized to one of 3 groups: (1)
      supracervical Foley catheter and intravaginal dinoprostone gel, (2) supracervical
      Foley catheter and 100 microg oral doses of misoprostol, or (3) serial 100-microg
      oral doses of misoprostol. Intravenous oxytocin was administered when a
      protraction disorder of labor was identified. RESULTS: There were 339 women
      randomized. There was no significant difference in the time from first
      intervention to delivery in the 3 groups (P =.546). In each group, a similar
      percentage of women required oxytocin (P =.103). The rates of cesarean delivery
      were equivalent among the groups (P =.722). Rates of tachysystole were high but
      statistically equivalent among the 3 groups. There were no significant
      differences in Apgar scores or umbilical artery pH. CONCLUSION: Oral 100 microg
      serial doses of misoprostol, with or without the use of a supracervical Foley
      catheter, were equivalent to the use of a supracervical Foley catheter and serial
      4-mg doses of dinoprostone gel for cervical ripening and the induction of labor.

PMID- 12066086
TI  - Procedural risks versus theology: chorionic villus sampling for Orthodox Jews at
      less than 8 weeks' gestation.
AB  - OBJECTIVE: According to Orthodox Jewish law, abortion is only permitted before 40
      days post conception. This evaluation was performed to determine the feasibility
      and safety of performing chorionic villus sampling (CVS) at 7 to 8 weeks'
      gestation so that genetic results would be useful for these patients. STUDY
      DESIGN: We evaluated a sequential series of 82 Orthodox Jewish patients who chose
      CVS at <63 days' gestation. Outcome measures included procedure success rates,
      laboratory success rates, pregnancy outcomes, and complications. RESULTS: CVS was
      successful in all cases. Ninety-one percent were performed transcervically, with
      30% requiring 2 or more insertions. Abnormal results were found in 16 (20%). Of
      61 cases with normal genetic and ultrasound results, spontaneous losses at less
      than 28 weeks occurred in 3 (5%). These rates are higher than the 2.3% loss rate
      and the 1.2% multiple insertion rate seen at our center when sampling is
      performed at the usual gestational ages of 10 to 12 weeks. One baby had a severe
      limb reduction defect (1.6%). CONCLUSION: In very experienced hands, CVS can be
      safely and reliably performed at very early gestational ages. The ability to
      obtain an early diagnosis may be associated with increased but acceptable
      complication rates, including a 1% to 2% risk of limb reduction defects. There
      are patients for whom the usual paradigms do not suffice, and obtaining an early
      disgnosis provides them the opportunity to trade increased risks for reproductive
      choice. The ethical issues are complex, but such decisions can be supported by
      extensive and detailed informed consent.

PMID- 12066087
TI  - Prematurity in multiple gestations: identification of patients who are at low
      risk.
AB  - OBJECTIVE: The purpose of this study was to evaluate a strategy for the
      identification of patients with multiple gestations who are at low risk for
      preterm delivery. STUDY DESIGN: A prospective observational study among patients
      with twin and triplet gestations. At 20 and 24 weeks of gestation, screening for
      bacterial vaginosis and fetal fibronectin was performed, followed by digital and
      sonographic assessment of the cervix. The treating physicians were blinded to
      test results. RESULTS: At the 24-week examination, specificities for delivery at
      >32 weeks of gestation for digital examination (92.9%), fetal fibronectin level
      (93.9%), cervical length on sonographic scan (85.1%), and combined fetal
      fibronectin level and cervical length (81.3%) did not differ statistically.
      Negative predictive values for these tests were >or=95%. All tests performed
      better at 24 weeks of gestation than at 20 weeks of gestation. CONCLUSION: At 24
      weeks of gestation, a normal digital examination, a negative fetal fibronectin
      level, a normal cervical length on sonographic scan, or the combination of a
      negative fetal fibronectin level and a normal cervical length each confer a
      similarly high likelihood of delivery at >32 weeks of gestation in women with
      multiple gestations.

PMID- 12066088
TI  - Acceptance of altering the standard 21-day/7-day oral contraceptive regimen to
      delay menses and reduce hormone withdrawal symptoms.
AB  - OBJECTIVE: Measure acceptance and use of extending the number of active oral
      contraceptive (OC) pills beyond 21 days and/or shortening the hormone-free
      interval to reduce the frequency and severity of hormone withdrawal symptoms.
      STUDY DESIGN: A retrospective review was performed of patients on OCs with
      unwanted hormone withdrawal symptoms who were counseled by one osbtetrician
      gynecologist (P. J. S.) on altering their standard 21/7 regimen. All patients
      used a monophasic 30 to 35 microg pill and underwent an initial counseling visit
      between December 1993 and October 2000. RESULTS: Of 318 patients counseled on
      "extending the number of active pills," 292 (92%) had documented follow-up after
      the initial counseling session. The primary reason for extending the number of
      active pills was to decrease symptoms of headache (35%), dysmenorrhea (21%),
      hypermenorrhea (19%), and premenstrual symptoms (13%). The remaining 12% of
      patients cited convenience, endometriosis, and other reasons such as menstrual
      associated acne. Twenty-five (9%) of 292 chose not to extend, with a preference
      for monthly menses as the most common reason (40%) followed by a concern that
      symptoms were not severe enough to warrant extension (32%). Of 267 patients who
      initiated an extended regimen, 57 discontinued OCs, 38 returned to a standard
      regimen, and 172 were extending use at the time of last follow-up. Using survival
      analysis methods, at 5 years 46% +/- 5% (mean +/- SE) of patients continued an
      extended OC pattern. The regimen of OC use by patients continuing an extended
      pattern was 12 +/- 12 (mean +/- SD) weeks of active pills (median of 9 weeks and
      range to 104 weeks) with pill-free interval of 6 +/- 2 days (median of 5 days and
      range of 0-7 days). CONCLUSION: The majority of patients with hormone withdrawal
      symptoms on OCs will initiate a regimen of extending active pills, often with a
      shortened hormone-free interval to reduce frequency and severity of associated
      symptoms.

PMID- 12066089
TI  - Cocaine use and preterm premature rupture of membranes: improvement in neonatal
      outcome.
AB  - OBJECTIVE: Our aim was to determine whether cocaine use increases neonatal
      morbidity in patients with preterm premature rupture of membranes. STUDY DESIGN:
      We reviewed records of pregnancies that were complicated with preterm premature
      rupture of membranes between 24 weeks to 34 weeks of gestation. Clinical
      characteristics and neonatal outcomes of patients who had positive results for
      cocaine in the urine were compared with patients with negative test results.
      RESULTS: During the study period, 16.1% (85/528 patients) had a positive result
      in a urine screen for cocaine use. Patients who used cocaine were older and of
      higher gravidity and parity. When major neonatal morbidities were compared, there
      was improvement in morbidities that were linked to neonatal infection in patients
      with positive test results for cocaine, including pneumonia (3.5% vs 11.7%; P
      =.012) and sepsis (5.9% vs 14.7%; P =.016). Jointly, neonatal outcomes were
      significantly worse in the negative cocaine group (chi(2) = 5.143; P =.023).
      CONCLUSION: The association of preterm premature rupture of membranes with major
      neonatal morbidity was unexpectedly and significantly weaker in pregnancies
      complicated by cocaine use.

PMID- 12066090
TI  - A comparison of preoperative and intraoperative evaluations for patients who
      undergo site-specific operation for the correction of pelvic organ prolapse.
AB  - OBJECTIVE: We compared preoperative and intraoperative assessments of pelvic
      organ prolapse to ascertain whether differences existed. STUDY DESIGN: This study
      is a retrospective analysis of information that was collected of 193 women who
      underwent reconstructive operation for pelvic organ prolapse between January 1994
      and April 1999 by the senior author (B. L. S.) in this institution. Support for
      the urethra, bladder, cervix or vaginal cuff, cul-de-sac, and rectum were
      assessed with the Baden-Walker halfway system before and during the operations.
      RESULTS: Preoperative and intraoperative assessments were significantly
      correlated (Spearman rank order correlation, 0.85-0.94). A comparison of the
      assessments revealed significantly greater prolapse at the urethra, cervix/cuff,
      cul-de-sac, and rectum on intraoperative evaluation (P <or=.00007). CONCLUSION:
      Intraoperative evaluation of women who are to undergo reconstructive operation
      for pelvic organ prolapse may reveal greater prolapse at selected sites than
      previously noted in up to 32% of patients.

PMID- 12066091
TI  - Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity.
AB  - OBJECTIVE: The purpose of this study was to describe the prevalence of and
      correlates for pelvic organ prolapse. STUDY DESIGN: This was a cross-sectional
      analysis of women who enrolled in the Women's Health Initiative Hormone
      Replacement Therapy Clinical Trial (n = 27,342 women). Baseline questionnaires
      ascertained demographics and personal habits. A baseline pelvic examination
      assessed uterine prolapse, cystocele, and rectocele. Descriptive statistics and
      logistic regression models were used to investigate factors that were associated
      with pelvic organ prolapse. RESULTS: In the 16,616 women with a uterus, the rate
      of uterine prolapse was 14.2%; the rate of cystocele was 34.3%; and the rate of
      rectocele was 18.6%. For the 10,727 women who had undergone hysterectomy, the
      prevalence of cystocele was 32.9% and of rectocele was 18.3%. After controlling
      for age, body mass index, and other health/physical variables, African American
      women demonstrated the lowest risk for prolapse. Hispanic women had the highest
      risk for uterine prolapse. Parity and obesity were strongly associated with
      increased risk for uterine prolapse, cystocele, and rectocele. CONCLUSION: Pelvic
      organ prolapse is a common condition in older women. The risk for prolapse
      differs between ethnic groups, which suggests that the approaches to risk-factor
      modification and prevention may also differ. These data will help address the
      gynecologic needs of diverse populations.

PMID- 12066092
TI  - Multimodal therapy including neoadjuvant methotrexate, vinblastine, doxorubicin,
      and cisplatin (MVAC) for stage IIB to IV cervical cancer.
AB  - OBJECTIVE: The purpose of this study was to determine the survival rates and
      toxicity levels that are associated with multimodal therapy (including
      neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC]) in
      patients with stage IIB to IVB cervical cancer. STUDY DESIGN: We retrospectively
      reviewed the cases of 49 patients who were treated between 1989 and 1997 with
      neoadjuvant MVAC for advanced cervical cancer. RESULTS: The clinical response
      rate was 90% (27 partial responders, 17 complete responders). Grade 3 or greater
      toxicity was mostly limited to neutropenia; no deaths were attributed to MVAC.
      Combined therapy after MVAC included operation in 34 patients (69%) and radiation
      in 41 patients (84%). Twenty-one patients (43%) had <2 cm residual tumor at
      histologic evaluation. Pelvic control was achieved in 86% of patients. Five-year
      disease-specific survival for patients with stage III disease was 60%.
      CONCLUSION: For patients with advanced cervical cancer, neoadjuvant MVAC had a
      high response rate (90%) and an acceptable toxicity level. Compared with historic
      control subjects, multimodal treatment may be associated with improved rates of
      pelvic control.

PMID- 12066093
TI  - Late postpartum eclampsia: a preventable disease?
AB  - OBJECTIVE: The purpose of this study was to determine whether there is a shift in
      the timing of eclampsia in relation to delivery and whether traditional symptoms
      precede impending postpartum eclampsia. STUDY DESIGN: A multicenter analysis of
      data from patients with eclampsia from March 1996 through February 2001 at the
      University of Cincinnati, the University of Tennessee, Memphis, and Central
      Baptist Hospital, Lexington. Data were collected regarding the relationship of
      the patient's first seizure to delivery, prodromal symptoms, neuroimaging
      studies, use of magnesium sulfate, antihypertensive therapy, and follow-up
      medical care. The analysis focused on women who had late postpartum eclampsia.
      RESULTS: During the study period, 89 patients were diagnosed with eclampsia.
      Twenty-nine women (33%) had postpartum eclampsia, of whom 23 women (79%) had late
      onset (>48 hours). Interestingly, only 5 of these 23 women (22%) had been
      previously diagnosed with preeclampsia. Twenty-one patients (91%) with late
      postpartum eclampsia had at least 1 prodromal symptom, and 12 patients (52%) had
      >1 symptom that heralded the seizure: 20 women (87%) had headache; 10 women (44%)
      had visual changes; 5 women (22%) had nausea or vomiting; and 2 women (9%)
      experienced epigastric pain. Only 7 of these 21 women (33%) sought care for their
      symptoms, of whom 6 women (86%) had clinical evidence of preeclampsia that was
      not considered by the treating physician. Among all patients with eclampsia,
      there were 7 cases of aspiration pneumonia, 3 cases of pulmonary edema, 3 cases
      of pleural effusion, 2 cases of disseminated intravascular coagulation, and no
      cases of maternal death. CONCLUSION: Current obstetric treatment in the United
      States has resulted in a shift of eclampsia toward the postpartum period, with
      most cases being seen as late post partum. To reduce the rate of late postpartum
      eclampsia, efforts should be directed to the education of the health care
      providers and patients regarding the importance of prompt reporting and
      evaluation of symptoms of preeclampsia during the postpartum period.

PMID- 12066094
TI  - Evidence for fetal involvement in the pathologic process of clinical
      chorioamnionitis.
AB  - OBJECTIVE: Clinical and histologic chorioamnionitis have recently been identified
      as risk factors for cerebral palsy. Proinflammatory cytokines have been
      implicated in the mechanisms that are responsible for brain injury in cases of
      intrauterine infection. The purpose of this study was to determine whether
      clinical chorioamnionitis, which is a maternal syndrome, is associated with an
      elevation in the fetal plasma interleukin-6 (IL-6) that is indicative of fetal
      inflammation. STUDY DESIGN: A cross-sectional study was designed to determine
      plasma concentrations of IL-6 in umbilical venous blood from patients with
      clinical chorioamnionitis (n = 26) and a control group (n = 111). Umbilical cord
      blood was obtained at the time of delivery. Plasma concentrations of IL-6 were
      measured with a sensitive and specific immunoassay. Nonparametric statistics were
      used for analysis. RESULTS: Plasma concentrations of IL-6 were detectable in all
      samples of umbilical venous plasma. The median concentration of plasma IL-6 was
      higher in neonates born to mothers with clinical chorioamnionitis than in
      neonates born to mothers in the control group (clinical chorioamnionitis: median,
      27.46 pg/mL; range, 1.3-5550.0 pg/mL; vs control: median, 2.13 pg/mL; range, 0.6
      812.3 pg/mL; P <.001). Sixty-two percent of neonates (16/26) who were born to
      women with clinical chorioamnionitis had fetal plasma concentrations of IL-6 >11
      pg/mL and 54% (14/26) had fetal plasma concentrations of IL-6 >18 pg/mL (these
      cutoff points have been used previously to define the fetal inflammatory response
      syndrome). CONCLUSION: Umbilical vein plasma concentrations of interleukin-6 are
      elevated in the neonates who were born to mothers with clinical chorioamnionitis,
      which suggests that the inflammatory process that is responsible for the maternal
      syndrome of clinical chorioamnionitis frequently involves the human fetus.

PMID- 12066095
TI  - Interventional magnetic resonance imaging cryotherapy of uterine fibroid tumors:
      preliminary observation.
AB  - OBJECTIVE: The purpose of this study was to identify alternatives to
      hysterectomy. We have developed a transabdominal interventional magnetic
      resonance imaging-guided cryoablation procedure and report this novel approach.
      STUDY DESIGN: This represents the preliminary and first report of a prospective
      Institutional Review Board-approved protocol to study interventional magnetic
      resonance imaging-guided cryoablation of uterine fibroid tumors. Women were
      selected on the basis of symptoms that were related to uterine fibroid tumors
      (bleeding, uterine pain, pelvic congestion, compression symptoms) and the absence
      of any desire for child bearing. A physical examination confirmed the presence of
      fibroid tumors, and magnetic resonance imaging was performed before the procedure
      to measure the size and number of fibroid tumors. Patients returned to the
      interventional magnetic resonance imaging and underwent placement of 3 to 5
      probes (2-3 mm) under magnetic resonance imaging-directed guidance. Follow-up
      magnetic resonance imaging determined the size reduction of the lesion, and a
      clinical evaluation determined the change in symptoms. RESULTS: Nine patients
      were treated and had substantial reduction in the uterine size (average, 66%
      volume reduction), and their primary symptoms have either improved or resolved.
      CONCLUSION: This is the first reported review of interventional magnetic
      resonance imaging-directed cryotherapy of uterine fibroid tumors. This minimally
      invasive therapy produced shrinkage of the tumor in 8 of our first 9 patients.

PMID- 12066096
TI  - A randomized trial of postoperative wound irrigation with local anesthetic for
      pain after cesarean delivery.
AB  - OBJECTIVE: The purpose of this study was to investigate the efficacy of
      continuous local anesthetic infusion system for pain control after cesarean
      delivery. STUDY DESIGN: This was a randomized prospective double-blind study.
      Patients who underwent cesarean delivery had a pain system implanted
      subcutaneously after closure of the fascia. Patients were randomized to receive
      an infusion of either 0.25% bupivacaine (n = 20) or normal saline solution (n =
      16) into the wound for 48 hours. Postoperative pain (determined with a visual
      analog scale) and postoperative morphine use were assessed at 12, 24, and 48
      hours. RESULTS: There were no significant differences in patient demographics or
      visual analog pain scores at any time interval between the bupivacaine versus the
      placebo group. However, narcotic requirements to produce this amount of pain
      relief were significantly less in patients who received bupivacaine infusion
      rather than normal saline solution at all time intervals. CONCLUSION: The
      continuous local anesthetic infusion system appears to be effective in reducing
      postoperative morphine use after cesarean delivery.

PMID- 12066097
TI  - Oral methotrexate for treatment of ectopic pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate oral methotrexate tablets in
      the treatment of ectopic pregnancy. STUDY DESIGN: Patients with a diagnosis of
      ectopic pregnancy were offered oral methotrexate tablets rather that
      intramuscular injection. Oral methotrexate was given in 2 divided doses 2 hours
      apart at a dose of 60 mg/m(2) with standard 2.5 mg methotrexate tablets. Patients
      were followed up with the use of the same protocol that was used typically for
      intramuscular methotrexate. RESULTS: Nineteen of 22 patients (86%) were
      successfully treated. There was no statistical difference between patients who
      were treated successfully or unsuccessfully, with respect to initial human
      chorionic gonadotropin titers (P =.55), ectopic size (P =.77), or methotrexate
      dose (P =.18). Nineteen of 22 patients (86%) had increased pain during treatment.
      Outside of pain, gastrointestinal side effects were the most common. Thirty-two
      percent of patients required more than one treatment cycle. CONCLUSION: Oral
      methotrexate can be used to treat ectopic pregnancy successfully, but there are
      few advantages to recommend its use over intramuscular methotrexate.

PMID- 12066098
TI  - Bedlam beggars, Winchester geese, and mewling infants: medicine and women's
      health issues in Shakespeare: presidential address.

PMID- 12066099
TI  - The expression of EP3-6 and inducible nitric oxide synthase messenger RNA are
      correlated in pregnant and misoprostol-treated but not in nongravid or menopausal
      myometrium.
AB  - OBJECTIVE: Our purpose was to investigate the expression level of inducible
      nitric oxide synthase (iNOS) in nongravid and gravid human myometrium and assess
      its relation to the expression of EP3 prostaglandin receptor isoforms. STUDY
      DESIGN: Myometrial tissue from a cohort of gravid, nongravid, and menopausal
      subjects and from nongravid subjects exposed to misoprostol was obtained and
      analyzed for iNOS messenger RNA (mRNA) expression and compared with previously
      determined mRNA levels for the EP3-6 prostaglandin receptor from the same samples
      by means of semiquantitative polymerase chain reaction. RESULTS: Significantly
      higher levels of iNOS mRNA expression were found in the gravid compared with
      premenopausal nongravid (P <.02) and menopausal (P <.05,) samples. Linear
      regression analysis of iNOS versus EP3-6 expression showed a positive correlation
      between all studied samples (n = 47, P <.0001, r = 0.815). Among individual
      groups, a significant linear correlation was found only in pregnant (n = 10, P
      <.0001, r = 0.785) and misoprostol-exposed (n = 7, P =.0256, r = 0.815) subjects.
      No correlation between iNOS and EP3-6 mRNA levels was noted in the nongravid
      premenopausal groups (n = 10, P =.205, r = 0.350), although a nonsignificant
      trend was found for the menopausal group (n = 10, P =.0535, r = 0.624). When the
      data from pregnant patients were stratified, both laboring and nonlaboring women
      displayed the observed correlation (n = 6, P <.0001, r = 0.993; and n = 13, P
      =.008, r = 0.697, respectively). CONCLUSION: iNOS and EP3-6 expression are
      strongly correlated in gravid and misoprostol-treated, nongravid myometrium.

PMID- 12066101
TI  - Erb's palsy contrasted with Klumpke's and total palsy: different mechanisms are
      involved.
AB  - OBJECTIVE: The purpose of this study was to examine the available evidence
      regarding the nature of the forces that were involved in the production of a
      lower plexus palsy or a total (whole arm) palsy, as contrasted with the nature of
      the forces that resulted in an upper plexus palsy. STUDY DESIGN: This was a
      review of studies that dealt with specific mechanisms that were supplemented by
      reports of total palsy that were gleaned from the literature and case reports
      from the clinical and medical legal cases of the authors. RESULTS: Studies of the
      forces involved in brachial plexus injury in adults and from cadaver studies in
      infants who were stillborn or who died in the newborn period attest to the nature
      of the forces needed to damage the lower plexus. This evidence is reinforced by
      the case reports. CONCLUSION: Forces other than simple widening of the head
      shoulder angle are necessary to disrupt the roots or cords of the lower brachial
      plexus. The position of the arm and direction of the forces that are applied
      determine the nature of the lesion.

PMID- 12066100
TI  - The effects of cardiovascular dynamics monitoring in the outpatient management of
      pregnancy hypertension.
AB  - OBJECTIVE: Our purpose was to assess the effects of the adjunctive use of
      cardiovascular dynamics monitoring in the ambulatory management of 199 pregnant
      patients with severe hypertension. STUDY DESIGN: A prospective, observational
      study was performed. Determinants of mean arterial pressure were computed by
      using the Hon monitor. Indicators of arterial compliance and effective blood
      volume were developed. All patients were monitored in the outpatient clinic;
      additionally, 19 patients self-tested at home. No rigid medication protocol was
      followed, but furosemide was used in most cases when cardiovascular dynamics
      monitoring patterns were consistent with volume loading. Otherwise, vasodilators
      were prescribed. The t test for independent samples was used to compare the home
      monitored subgroup with the outpatient-only group. RESULTS: Pregnancy was
      prolonged by 74 +/- 63.9 days (mean +/- SD). Mean gestation was 37.6 +/- 2.9
      weeks, and mean birth weight was 2882.4 +/- 837 g. The primary cesarean delivery
      rate was 23.7%, but only 15 (7.5%) cesarean deliveries were performed because of
      failed therapy. The 19 home-monitored patients gained 108 +/- 75 days (83.1 +/-
      42.2 days beyond 20 weeks). CONCLUSION: Adjunctive cardiovascular dynamics
      monitoring may have a role in the evaluation and management of hypertension
      during pregnancy.

PMID- 12066102
TI  - Recommendations for repeat courses of antenatal corticosteroids: a decision
      analysis.
AB  - OBJECTIVE: The objective was to review the evidence regarding multiple versus
      single courses of antenatal corticosteroids (ACS), devise dosing regimens based
      on this evidence, and then, by using decision analysis, compare 5 ACS regimens:
      (1) single course, (2) weekly courses, (3) every-other-week dosing, (4) every
      other-week dosing with no more than 2 courses, and (5) an every-other-week dosing
      regimen with no third courses after 30 weeks and no second course after 32 weeks.
      STUDY DESIGN: The literature was examined for evidence regarding a dose response
      of the benefits and detriments of ACS. A decision analytic model was designed by
      using odds ratios, risks of morbidity and mortality, and birth rates from the
      literature. Mathematic modeling, based on data in the literature, was used to
      estimate the number of patients who would present at risk for preterm delivery
      and at what gestational age they would subsequently be delivered. A sensitivity
      analysis was performed to account for uncertainties in the data. RESULTS: Of
      approximately 4 million annual births in the United States, a conservative
      estimate of 138,000 patients will present between 24 and 34 weeks of gestation at
      risk for preterm delivery, with 91,915 deliveries. If the 5 different dosing
      regimens are applied to these patients, strategy 1, the single course of ACS,
      would result in 30,232 cases of respiratory distress syndrome (RDS) and 4032
      neonatal deaths. Three of the other dosing regimens (2, 3, and 5) would all
      decrease the number of cases of RDS but would concomitantly increase neonatal
      deaths. Only dosing regimen 4 would decrease the cases of RDS by 2187 without
      increasing the number of neonatal deaths. CONCLUSION: There is evidence that
      there may be a decrease in the incidence of RDS secondary to the use of multiple
      doses of ACS; however, a concomitant increase in neonatal deaths may also occur.
      On the basis of our results, we recommend the following: (1) all fetuses between
      24 and 34 weeks' gestation at risk for preterm delivery should be given the first
      course, (2) if there is a persisting risk of preterm delivery subsequent to this,
      the next course should be given 2 weeks later, and (3) no more than 2 courses
      should be given. These recommendations need to be examined in a randomized,
      controlled trial.

PMID- 12066103
TI  - Neonatal outcomes in immediate versus delayed conceptions after spontaneous
      abortion: a retrospective case series.
AB  - OBJECTIVE: This study was undertaken to determine differences in neonatal
      outcomes between successful pregnancies conceived immediately after a spontaneous
      abortion (SAB) and successful pregnancies conceived after two menstrual cycles or
      at least 100 days from the spontaneous abortion. STUDY DESIGN: This study was a
      retrospective case series. Deliveries were identified from the University of
      California-San Francisco Perinatal Database among patients with a history of one
      SAB. Medical records of 268 patients were reviewed. Sixty-four patients fulfilled
      study criteria, with 19 in the immediate conception group and 45 in the delayed
      conception group. Categorical variables were analyzed using chi(2) tests and
      Fisher exact tests for variables with expected values of <5, whereas continuous
      variables were analyzed using Student t tests. RESULTS: Neonatal outcomes for the
      2 groups were similar, although neonates in the delayed conception group were
      more likely to have at least one of the following: low birth weight, an Apgar
      score <7 at 5 minutes, or admission to the neonatal intensive care unit.
      CONCLUSION: In this small retrospective case series, there was no evidence of
      adverse neonatal outcomes associated with conception immediately after a SAB.

PMID- 12066104
TI  - Factors affecting the likelihood of successful induction after intravaginal
      misoprostol application for cervical ripening and labor induction.
AB  - OBJECTIVE: Our purpose was to determine whether maternal age, height and weight,
      parity, duration of pregnancy, cervical dilatation or Bishop score, and birth
      weight could be used to predict the likelihood of successful induction in women
      given intravaginal misoprostol. STUDY DESIGN: A computerized database was
      compiled of 1373 pregnancies in which intravaginal misoprostol was given for
      cervical ripening and labor induction. Most of these women were placed on
      investigational protocols in which the dose of misoprostol administered was 25 to
      50 microg and the dosing intervals ranged from 3 to 6 hours. No more than 24
      hours of administration was permitted. Induction was undertaken in women with
      unfavorable cervical examinations (Bishop scores of 4 or less) and without
      spontaneous labor or ruptured membranes. Univariate and stepwise multiple
      regression analyses were performed to identify those factors associated with
      successful induction, defined as vaginal delivery within 24 hours of induction.
      RESULTS: Six hundred fifty-seven (48%) had successful induction. Parity (odds
      ratio [OR] 2.5, 95% CI 2.0-2.9, P <.0001), initial cervical dilatation (OR 1.9,
      95% CI 1.6-2.3, P <.0001), Bishop score (OR 1.6, 95% CI 1.3, 1.8, P <.0001), and
      gestational age at entry (OR 1.3, 95% CI 1.1-1.5, P =.002) were significant at
      the.05 level for predicting successful induction. A multivariate stepwise
      logistic regression was then performed to evaluate each of these as independent
      predictors. Parity (OR 2.4, 95% CI 2.0-3.0, P <.0001), initial cervical
      dilatation (OR 1.7, 95% CI 1.4-2.1, P <.0001), and estimated gestational age (OR
      1.3, 95% CI 1.1-1.6, P =.003) are significant independent predictors for
      successful induction, but initial Bishop score is not significant (P =.19) after
      adjustment for other significant predicting factors. CONCLUSIONS: The clinical
      characteristics of parity, initial cervical dilatation, and gestational age at
      entry are predictors of the likelihood of success of cervical ripening and labor
      induction with intravaginal misoprostol administration.

PMID- 12066105
TI  - Assessing the risk of multiple gestation in gonadotropin intrauterine
      insemination cycles.
AB  - OBJECTIVE: The purpose of this study was to analyze factors for their ability to
      predict multiple gestation in women who undergo controlled ovarian
      hyperstimulation with gonadotropins (follicle-stimulating hormone/human
      menopausal gonadotropin) and intrauterine insemination. STUDY DESIGN: This was a
      retrospective analysis of the clinical and laboratory variables that are
      associated with multiple gestation. Data for 6 variables in 678 cycles of
      gonadotropin/intrauterine insemination between 1990 and 1999 were analyzed with
      survival analysis, Cox regression analysis, and multiple logistic regression.
      RESULTS: There were 99 clinical pregnancies among 678 cycles (14.6% per cycle) in
      306 women. Of the 14 women with multiple gestations (14.1% of pregnancies), 11
      women had twins, 2 women had triplets, and 1 woman had quadruplets. Age, days of
      gonadotropin treatment, total dose of gonadotropin, and number of follicles that
      were >or=15 mm at the time of human chorionic gonadotropin administration were
      statistically significant predictors of multiple gestation in >or=1 of the
      statistical models. CONCLUSION: The risk of multiple gestation with controlled
      ovarian hyperstimulation/intrauterine insemination in this study was relatively
      low. In addition to age, several controllable variables that are associated with
      multiple gestation were identified.

PMID- 12066106
TI  - Impact of early postpartum administration of progestin-only hormonal
      contraceptives compared with nonhormonal contraceptives on short-term breast
      feeding patterns.
AB  - OBJECTIVE: The purpose of this study was to identify the impact on breast-feeding
      patterns of early postpartum initiation of progestin-only birth control methods
      compared with nonhormonal methods. STUDY DESIGN: A prospective, nonrandomized
      trial was performed comparing progestin-only contraceptive methods administered
      before hospital discharge with nonhormonal methods on breast-feeding continuation
      rates, exclusive breast-feeding, and supplementation at 2, 4, and 6 weeks after
      delivery. RESULTS: Three hundred nineteen women provided complete data until
      hospital discharge. The hormonal group had higher risk factors for not breast
      feeding, but there was no difference among any of the subgroups in breast-feeding
      continuation rates except at week 4. Supplementation or perception of
      insufficient milk production did not differ between groups. By week 6, 23.5% of
      women discontinued breast-feeding, and 64.5% of those breast-feeding were
      supplementing. CONCLUSION: This study demonstrates that there is no detectable
      adverse impact on breast-feeding attributable to progestin-only contraceptive
      methods initiated within the first 3 days post partum.

PMID- 12066107
TI  - A review of medical and allied health learners' satisfaction with their training
      in women's health.
AB  - OBJECTIVE: Graduating learners from Oregon Health and Sciences University
      programs and from the National College of Naturopathic Medicine were surveyed
      about their attitudes toward their training in women's health. STUDY DESIGN: The
      survey addressed learner satisfaction with training in women's health, their
      preferred learning methods, and their clinical comfort in managing 17 clinical
      problems. The survey addressed knowledge of complementary and alternative
      medicine. RESULTS: Satisfaction with training in women's health varied by
      program. Satisfaction increased with increasing proportion of women seen during
      training. Clinical confidence scores increased with increasing proportion of
      women seen during training. Physical assault and breast disease were areas of
      least clinical confidence. All groups preferred learning in clinical rather than
      didactic settings. Experience with alternative and complementary medicine was
      very limited except among naturopathic students. CONCLUSIONS: Areas of common
      educational need were identified among a variety of learners. This information
      will assist educators in designing multidisciplinary programs to meet the needs
      of this diverse group.

PMID- 12066108
TI  - Hormonal manipulation in women with chronic, cyclic irritable bladder symptoms
      and pelvic pain.
AB  - OBJECTIVE: Chronic, painful bladder symptoms are diagnostic and therapeutic
      challenges for urologists and gynecologists. The aims of this study were to
      evaluate women with menstrual cycle-related changes in their interstitial
      cystitis symptoms, to treat them with hormonal manipulation, and to follow them
      long term. STUDY DESIGN: The cases of women who were referred to a tertiary care
      center with interstitial cystitis and menstrual cycle exacerbation of symptoms
      were evaluated in a retrospective study. Fifteen women had undergone laparoscopy
      that was followed immediately by cystoscopy and bladder hydrodistension. Patients
      were then treated with leuprolide acetate or oral contraceptive pills. RESULTS:
      Patient age ranged from 23 to 48 years. The duration of symptoms ranged from 1 to
      26 years. Ten patients (67%) had findings of both interstitial cystitis and
      peritoneal endometriosis. Five of 15 patients (33%) had interstitial cystitis,
      but no endometriosis was found. Symptoms improved for 8 of 9 women who were
      treated with leuprolide acetate and for 5 of 6 women who were treated with oral
      contraceptive pills. Patients were followed up for an average of 55 months.
      CONCLUSION: Diagnostic laparoscopy should be considered together with
      hydrodistension of the bladder for women with pelvic pain and irritative bladder
      symptoms that are exacerbated premenstrually. Endometriosis is often present in
      patients with these complex symptoms. This is the first report of hormonal
      treatment for chronic, cyclic irritative bladder symptoms; improvement appears to
      occur even when endometriosis is not identified by laparoscopy.

PMID- 12066109
TI  - Frequency of symptomatic cornual hematometra and postablation tubal sterilization
      syndrome after total rollerball endometrial ablation: a 10-year follow-up.
AB  - OBJECTIVE: This study was undertaken to determine the frequency of symptomatic
      cornual hematometra and postablation tubal sterilization syndrome after total
      rollerball endometrial ablation and to describe methods for diagnosis, treatment,
      and prevention. STUDY DESIGN: Retrospective cases of 50 consecutive patients who
      received total rollerball endometrial ablation for dysfunctional uterine bleeding
      were followed up for 10 years. RESULTS: Symptomatic cornual hematometra or
      postablation tubal sterilization syndrome was diagnosed by ultrasound scanning
      and/or magnetic resonance imaging in 5 of 50 patients (10%) who had a total
      endometrial ablation. Two patients had cornual hematometra, and 3 patients had
      postablation tubal sterilization syndrome 4 months to 90 months after rollerball
      ablation. Subsequent gonadotropin-releasing hormone agonist treatment or
      hysteroscopic decompression of the hematometra was only partially successful, and
      recurrence of symptoms necessitated hysterectomy with salpingectomy. CONCLUSION:
      Uterine contracture, which obstructs bleeding from persistent cornual endometrium
      and leads to symptomatic cornual hematometra or postablation tubal sterilization
      syndrome, is not uncommon after total rollerball endometrial ablation, with an
      incidence of 10% in our series. Satisfactory treatment requires hysterectomy with
      salpingectomy, but modifications such as partial endometrial ablation can prevent
      these complications.

PMID- 12066110
TI  - Characteristics of sexual assault in women with a major psychiatric diagnosis.
AB  - OBJECTIVE: In a previous study of women who had been sexually assaulted, we
      reported a 26% prevalence of a major psychiatric diagnosis. The purpose of this
      study was to better characterize sexual assaults in women with a major
      psychiatric diagnosis. STUDY DESIGN: All female patients >or=15 years old with a
      complaint of sexual assault underwent a standardized history and physical
      examination by an upper-level resident in obstetrics and gynecology. Data were
      abstracted and verified. A psychiatric diagnosis was determined by history and by
      use of computer-linked medical records. Chi-square or Fisher exact test was used
      for categoric analysis. RESULTS: Of the 819 women who were examined, 211 women
      (26%) had a major psychiatric diagnosis. In these 211 women, the prevalence of
      solely mood, thought, or substance use disorders were 26%, 14%, and 16%,
      respectively, whereas 44% had >or=2 diagnoses. Having a psychiatric diagnosis was
      associated with increasing age (P =.001), homelessness (P =.001), and
      incarceration (P =.001). In comparison with women with no psychiatric diagnosis,
      sexual assaults in these 211 women occurred more frequently outdoors (P =.007),
      by a stranger (P <.001), or by >or=2 assailants (P =.02). Being assaulted with a
      weapon (P =.04) and being hit (P =.01) were more prevalent in assaults against
      women with a psychiatric diagnosis, as was anal contact (P =.03), contact to
      >or=2 body orifices (P =.001), and body trauma (P =.01). CONCLUSION: Sexual
      assaults in women with a major psychiatric diagnosis are common. These assaults
      are more violent and result in body trauma more frequently than do sexual
      assaults in women without a psychiatric diagnosis. Prevention and treatment
      strategies should target this vulnerable population.

PMID- 12066111
TI  - Efficacy of tension-free vaginal tape with other pelvic reconstructive surgery.
AB  - OBJECTIVE: The tension-free vaginal tape procedure has been shown in several
      studies to be a safe and effective method of correcting stress urinary
      incontinence, but its efficacy when combined with other pelvic surgery has not
      been examined. STUDY DESIGN: Thirty-seven women with stress or mixed urinary
      incontinence and other pelvic floor defects underwent the tension-free vaginal
      tape procedure in conjunction with other pelvic floor reconstructive surgery.
      Preoperative and postoperative voiding diaries, standing stress test results, and
      patient satisfaction were evaluated. Patient outcome, operative difficulties, and
      complications are discussed. RESULTS: Thirty-five of 37 patients were completely
      dry (94%) 6 months after surgery. One patient (2.7%) had a recurrent pelvic floor
      defect. Four of 37 (10.8%) noted postoperative urgency that required treatment.
      The overall complication rate was 18.9%: the most common complication was urinary
      retention (43%); mean number of days with a catheter was 5.1 (range, 0-21 days).
      No serious operative complications occurred. Nine of 9 (100%) patients who
      underwent a repeat anti-incontinence procedure were cured with no increase in the
      complication rate. CONCLUSION: The tension-free vaginal tape procedure is safe
      and efficacious when combined with other pelvic floor reconstructive surgery.
      Postoperative urinary retention was the most common complication.

PMID- 12066112
TI  - Obstetric attending physician characteristics and their impact on vacuum and
      forceps delivery rates: University of California at San Francisco experience from
      1977 to 1999.
AB  - OBJECTIVE: The objective of our study was to determine the impact of obstetric
      attending physician characteristics (eg, region of previous residency training,
      sex, year of graduation from residency) on the rates of vacuum and forceps
      delivery at our institution. STUDY DESIGN: The analysis was based on 19,897
      vaginal deliveries that were performed by 171 attending physicians and 160
      resident physicians between 1977 and 1999 at the University of California at San
      Francisco Medical Center. Z -tests and multivariate logistic regression were
      performed on a perinatal database that contained standard obstetric variables.
      RESULTS: Male attending physicians had a higher percentage of forceps deliveries
      compared with female attending physicians (11.1% vs 6.6%; P <.001); female
      attending physicians had a higher percentage of vacuum deliveries compared with
      male attending physicians (9.8% vs 5.1%; P <.001). However, multivariate
      regression analysis revealed that only the year in which the procedure was
      performed affected both the forceps and vacuum delivery rates (P <.041). The
      region of previous residency training of the attending physician affected the
      vacuum delivery rate (P <.0001) but not the forceps delivery rate (P >.06) in
      multivariate logistic regression analysis. Factors such as the sex of the
      obstetric attending physician, the sex of the resident, and the year of
      graduation from residency for the obstetric attending physician did not have a
      significant impact on the forceps or vacuum delivery rates (all P >.05).
      CONCLUSION: Our study is the first to report that the apparent gender differences
      in forceps and vacuum delivery rates among obstetric attending physicians was due
      to the year in which the procedure was performed and not due to sex per se. We
      also found that the region of previous residency training for the obstetric
      attending physician significantly influenced the vacuum delivery rate.

PMID- 12066113
TI  - Paracervical block and elective abortion: the effect on pain of waiting between
      injection and procedure.
AB  - OBJECTIVE: Our purpose was to assess the effect on pain and patient satisfaction
      of waiting between paracervical block and dilation during first-trimester
      abortions. STUDY DESIGN: One hundred ninety-nine women seeking pregnancy
      termination were randomly assigned to a no-wait group (group 1) and a 3- to 5
      minute wait between injection and dilation group (group 2). Subjects rated their
      pain on a visual analog scale at four times: prior to procedure, with dilation,
      with aspiration, and 30 to 45 minutes after procedure. RESULTS: No significant
      differences were observed in pain or satisfaction ratings reported by group 1 (n
      = 93) and group 2 (n = 101). A significant decrease in pain with dilation (1.21
      cm decrease, P =.009) and aspiration (1.15 cm decrease, P =.0015) was observed
      among patients who received fentanyl. CONCLUSION: Delay between paracervical
      injection and dilation during first-trimester abortion does not have an impact on
      patient pain or satisfaction. Fentanyl decreased pain scores by 20% to 25% during
      the procedure.

PMID- 12066114
TI  - Aberrant expression of E-cadherin in cervical intraepithelial neoplasia
      correlates with a false-negative Papanicolaou smear.
AB  - OBJECTIVES: E-cadherin is responsible for cell adhesion in normal cervical
      epithelium. It is normally absent in the superficial epithelial layers, allowing
      for exfoliation. We investigated the correlation between E-cadherin distribution
      and Papanicolaou smear in subjects with cervical dysplasia. STUDY DESIGN: Tissue
      samples from 25 women with cervical dysplasia were tested for E-cadherin, beta
      catenin, and alpha-catenin expression by immunohistochemistry. The expression
      pattern of these proteins, whether full thickness or restricted to the basal
      layers, was correlated with the Papanicolaou smear result. RESULTS: Of 12 women
      with normal Papanicolaou smears, 10 of 11 informative cases demonstrated E
      cadherin expression throughout all epithelial layers. Eight of 10 informative
      cases with an abnormal Papanicolaou smear showed E-cadherin only at the basal
      layers. Alpha-catenin was distributed throughout the entire epithelium in samples
      of all 25 women. CONCLUSIONS: Expression of E-cadherin throughout all epithelial
      layers was correlated with a false-negative Papanicolaou smear. It is likely that
      aberrant persistence of E-cadherin in these lesions interferes with the
      exfoliation of abnormal cells.

PMID- 12066115
TI  - Perioperative changes in serum creatinine after gynecologic surgery.
AB  - OBJECTIVE: The purpose of this study was to prospectively determine the normal
      range of postoperative changes in serum creatinine levels when bilateral ureteral
      patency was confirmed by cystoscopy. STUDY DESIGN: A total of 187 consecutive
      patients who had undergone major gynecologic surgery were evaluated
      prospectively. All patients had undergone perioperative cystoscopy to evaluate
      for ureteral patency, and creatinine levels had been determined before and 24
      hours after surgery. RESULTS: The mean change in serum creatinine level was 0.01
      mg/dL, and the changes for the central 95% ranged from -0.2 to 0.3 mg/dL. With a
      previously defined cutoff value of an increase of >0.2 mg/dL after operation to
      indicate ureteral obstruction, specificity and negative predictive values (when
      compared with cystoscopic findings) were 98% and 100%, respectively. CONCLUSION:
      Creatinine levels change minimally during the immediate postoperative period in
      the absence of ureteral compromise. If bilateral ureteral patency was
      demonstrated after operation in our population, creatinine level elevations were
      always <0.3 mg/dL.

PMID- 12066116
TI  - Postpartum Chlamydia trachomatis and Neisseria gonorrhoeae infections.
AB  - OBJECTIVE: The purpose of this study was to investigate Chlamydia trachomatis and
      Neisseria gonorrhoeae infections that are diagnosed during the postpartum period
      (defined as the 3 months after delivery). STUDY DESIGN: This was a retrospective
      cohort study of women delivered of infants at >or=28 weeks of gestation at an
      urban hospital from 1992 through 1998, including each woman's first delivery
      during this period. Postpartum C trachomatis and N gonorrhoeae testing were
      routine. Data were extracted from an electronic medical record system. RESULTS:
      Of 13,086 women with eligible deliveries, 7258 women (55.5%) underwent postpartum
      C trachomatis tests; 191 of those women (2.6%) had positive test results.
      Similarly, 7148 women (54.6%) underwent postpartum N gonorrhoeae tests; 95 of
      those women (1.3%) had positive test results. Most women with positive postpartum
      tests had prenatal testing (182/191 with C trachomatis; 94/95 with N gonorrhoeae
      ), and the last prenatal test results were usually negative (153/182 women with
      negative prenatal C trachomatis testing; 91/94 women with negative prenatal N
      gonorrhoeae testing). CONCLUSION: Substantial rates of C trachomatis and N
      gonorrhoeae were found in postpartum women, most of whom had negative results on
      the last prenatal test.

PMID- 12066117
TI  - The impact of a single-layer or double-layer closure on uterine rupture.
AB  - OBJECTIVE: Our purpose was to measure the impact of a single-layer or double
      layer closure on uterine rupture at subsequent delivery. STUDY DESIGN: This is an
      observational cohort study of all women undergoing a trial of labor from 1988 to
      2000 in a tertiary care center, after a single low transverse cesarean delivery.
      Factors most highly associated with uterine rupture were identified by using
      univariate regression analysis. Multivariate logistic regression analysis was
      used to adjust for selected confounding variables. RESULTS: Of the 2142 women who
      met the study criteria, 1980 (92.4%) had maternal records and original operative
      reports reviewed. After adjustments were made for confounding variables, the odds
      ratio for uterine rupture in women with a single-layer closure was 3.95 (95% CI,
      1.35-11.49). CONCLUSION: A single-layer closure of the previous lower segment
      incision was the most influential factor and was associated with a 4-fold
      increase in the risk of uterine rupture compared with a double-layer closure.

PMID- 12066118
TI  - The labor curve of the grand multipara: does progress of labor continue to
      improve with additional childbearing?
AB  - OBJECTIVE: Our purpose was to test the hypothesis that progress of labor slows as
      parity exceeds 4 by comparing labor curves of grand multiparous women (para 5 and
      over) (GMs) with those of nulliparous and lower-parity multiparous women. STUDY
      DESIGN: Retrospective cohorts of spontaneously laboring, vertex-presenting, term
      GMs who were admitted to two medical centers during the period from January 1990
      through June 1995 were randomly computer-matched to a nulliparous and a lower
      parity multiparous control subject, matched for age, hospital, and year of
      delivery. Cervical examination data were graphed retrospectively from the time of
      full dilatation. Curves were compared by pairwise likelihood ratio tests, by
      using a random effects model to adjust for obstetric interventions, with
      significance set at P <.05. RESULTS: Pregnancies in 1095 GMs, 1174 lower-parity
      multiparous women, and 908 nulliparous women were studied. GMs exhibit a longer
      initial phase of labor than either nulliparous women or lower-parity multiparous
      women, begin to dilate rapidly at a greater dilatation than nulliparous women,
      and experience acceleration of labor at a rate no faster than lower-parity
      multiparous women. The average labor curve of GMs resembles that of nulliparous
      women before dilatation of 4 cm is attained, then transitions to the typical
      curve of the lower-parity multiparous women until dilatation of 6 cm is attained
      and thereafter is indistinguishable from that of the lower-parity multiparous
      women (P <.001). CONCLUSIONS: Once parity exceeds 4, progress of labor slows.
      "Poor progress" beyond dilatation of 4 cm should not be considered abnormal for a
      GM, because she is likely still in the latent phase until dilatation of 6 cm is
      attained. Nor should she be expected to progress through her active phase any
      faster than lower-parity multiparous women.

PMID- 12066119
TI  - Pushing in labor: performance and not endurance.
AB  - OBJECTIVE: It is believed that delivery is faster if women are instructed to
      voluntarily bear down in synchrony with their uterine contractions. Confronted by
      the large variance in the duration of the second stage of labor, many clinicians
      attribute a "fast" or a "short" expulsion time solely to the patient's
      willingness to cooperate or to the strength of epidural anesthesia if it is a
      factor. Yet, knowledge of pushing performance and the factors affecting it remain
      limited. We investigated the maternal, fetal, and labor characteristics that
      influence the maternal "pushing performance" and sought to design a predictive
      index that prospectively identified "high" versus "low" pushing performers. STUDY
      DESIGN: Intrauterine pressure (IP) was prospectively measured during the second
      stage of labor in 52 women recruited at one North American hospital. Recordings
      were begun after documentation of full cervical dilatation and descent of the
      fetal head to +2 station (on a -3/+3 scale). Each woman acted as her own control,
      received epidural anesthesia, and was alert and responsive throughout the study.
      Pushing (closed glottis technique) was performed in a standardized fashion.
      Multivariate analysis with linear regression was applied to identify significant
      associations between maternal, fetal, or labor characteristics as the independent
      variables and the percent increase in IP consequent to active pushing as the
      dependent variable. RESULTS: Women in labor increase their IP 62% by actively
      pushing with a contraction during the second stage. A scattergram of the
      individual percent increase above the baseline IP integral revealed that for some
      women, pushing more readily increased their IP than it did for others (range, 0%
      to 192%). The percent increase was best calculated by a linear combination of
      myometrial thickness, estimated fetal weight, the maternal body mass index, and
      the obstetric need for labor augmentation (P =.007, r = 0.52, power = 0.975). A
      66% change in IP provided the best separation between high and low pushing
      performance. Myometrial thickness provided the single strongest contribution to
      the regression equation's predictive value (P =.01, r = -0.36). A myometrial
      thickness of 6 mm had a specificity of 88% (but only 53% sensitivity) for the
      identification of women able to increase their IP by 66% over baseline.
      CONCLUSIONS: In women in labor who have received epidural anesthesia, the
      efficiency with which maternal expulsive efforts are converted into increased IP
      is directly related to the patient's body mass index but inversely related to
      myometrial thickness, the sonographic estimate of fetal weight, and the need for
      labor augmentation.

PMID- 12066120
TI  - Risk of preterm birth that is associated with vaginal douching.
AB  - OBJECTIVE: The purpose of this study was to examine the association between
      vaginal douching and preterm birth. STUDY DESIGN: We enrolled hospitalized women
      after delivery in a case-control study. Women who were delivered of a live
      preterm singleton infant were assigned as cases. Women who were delivered at term
      were randomly selected as control subjects. We surveyed women about their
      douching habits and risk factors for preterm birth and abstracted data from the
      records. RESULTS: After adjustment, vaginal douching within 6 months of pregnancy
      was not significantly associated with preterm birth (odds ratio, 1.1; 95% CI, 0.8
      1.6). However, in secondary analyses, douching more than once per week (odds
      ratio, 4.0; 95% CI, 1.0-15.5) or longer than 10 years (odds ratio, 1.9; 95% CI,
      1.1-3.2) was associated with preterm birth. CONCLUSION: Vaginal douching does not
      appear to be a strong risk factor for preterm birth. Further study is needed to
      confirm the risk that is associated with frequent or long-term douching.

PMID- 12066121
TI  - How well does reflectance pulse oximetry reflect intrapartum fetal acidosis?
AB  - OBJECTIVE: The purpose of this study was to determine the sensitivity and
      specificity for acidosis of intrapartum fetal oxygen saturation measured by
      reflectance pulse oximetry. STUDY DESIGN: Intrapartum fetal oxygen saturation
      values per labor stage were correlated with umbilical artery pH, base excess and
      PCO(2) by regression analysis. Receiver operating characteristic curve analysis
      was performed with the use of historic umbilical arterial cutoff values; a fetal
      oxygen saturation cutoff range with optimal sensitivity and specificity was
      calculated. RESULTS: Mean fetal oxygen saturation was 42.8%, over the mean 132
      minutes of 107 recordings. Overall areas under the sensitivity and specificity
      curves were 0.77 for pH and PCO(2), decreasing sharply toward birth; all areas
      for base excess were poor (approximately 0.5). Depending on stage and umbilical
      artery parameter, fetal oxygen saturation cutoffs were 33% to 36%, with
      sensitivities of 0.67 to 0.8 and specificities of 0.62 to 0.90. CONCLUSION: Fetal
      oxygen saturation sensitivities and specificities for acidosis do not yet justify
      the supplementation of cardiotocography with routine reflectance pulse oximetry.

PMID- 12066122
TI  - Regulation of c-fos expression by static stretch in rat myometrial smooth muscle
      cells.
AB  - OBJECTIVE: We investigated whether mechanical stretch stimulates expression of
      the immediate early gene c-fos messenger RNA in rat myometrial smooth muscle
      cells. STUDY DESIGN: Freshly isolated myometrial smooth muscle cells (from virgin
      rats) were plated on flexible culture plates that were coated with either
      collagen I, laminin, elastin, or pronectin and were subjected to a static stretch
      with a computerized strain unit. Immunocytochemistry was used to define smooth
      muscle cell phenotype, and c-fos expression levels were assessed by Northern
      blotting. RESULTS: Myometrial smooth muscle cells maintained their phenotype for
      at least 7 days in culture. Stretch induced a dramatic increase in levels of c
      fos messenger RNA, which peaked after 30 minutes. Stimulation of c-fos gene
      expression was dependent on the degree of stretch (maximum induction at 25%
      elongation). Interestingly, as little as 1 minute of stretch was sufficient to
      induce maximal c-fos expression at 30 minutes. The most dramatic induction of c
      fos was observed in smooth muscle cells that were stretched on collagen I-coated
      plates. CONCLUSION: Myometrial smooth muscle cells can directly respond to
      mechanical stretch with a strength- and matrix component-dependent increase in c
      fos messenger RNA. The time delay between the initial stimulus and the cumulative
      elevation of c-fos messenger RNA suggests a complex regulation from
      mechanoreception to c-fos gene expression.

PMID- 12066123
TI  - Prenatal HLA genotyping of uncultured amniotic fluid samples contaminated with
      maternal blood.
AB  - OBJECTIVE: Allogenic transplantation of umbilical cord blood (UCB) from HLA
      identical siblings is a therapeutic concept of increasing importance. Prenatal
      HLA typing results can provide important information as to whether the UCB should
      be collected. Therefore, we tested the suitability of two methods based on
      polymerase chain reaction (PCR) for low-resolution HLA genotyping of uncultured
      amniocytes contaminated with maternal blood. STUDY DESIGN: Amniotic fluid samples
      (~10 mL, n = 4) were collected and divided into 5 equal sized portions.
      Subsequently, maternal blood was added to produce a series of varying degrees of
      artificial contamination ranging from 0% to 5% (vol/vol). Corresponding maternal
      blood and cord blood samples were collected and served as reference material.
      After DNA preparation, all samples were subjected to both PCR-SSP (sequence
      specific primers) and PCR-SSO (sequence-specific oligonucleotides) typing
      procedures, designed for low-resolution typing of the highly polymorphic HLA-B
      locus. RESULTS: Both PCR tests were able to accurately predict the fetal HLA-B
      type when pure amniotic fluid was used in all cases. The PCR-SSP method could
      still determine the fetal HLA type at 0.1% contamination but not at levels above
      this; in contrast, PCR-SSO failed if any degree of contamination was present.
      CONCLUSION: Fetal cells from amniotic fluid represent a reasonable source for
      prenatal testing of the fetal HLA genotype with either the PCR-SSP or the PCR-SSO
      method. Low levels of contamination with maternal blood in the amniotic fluid are
      tolerated by the more robust PCR-SSP method. In contrast, the PCR-SSO procedure
      is more sensitive to any degree of contamination, but it is the method of choice
      if the amount of DNA is limited because of the very low volume of specimens of
      amniotic fluid available.

PMID- 12066124
TI  - Total and individual triplet birth weights as a function of gestational age.
AB  - OBJECTIVE: Our purpose was to determine the relationship between gestational age
      and both the total and individual triplet birth weights. STUDY DESIGN: A 1988
      2000 prospective cohort of 3238 live-born triplets in the United States was
      evaluated. The mean individual (heaviest, middle, and lightest) and total triplet
      birth weights were correlated with gestational age in nulliparous and multiparous
      patients. RESULTS: The mean total triplet birth weights significantly correlated
      with gestational age for both nulliparous women and multiparous women, but the
      respective regression lines were significantly different (P =.0018). The
      respective regression lines for individual triplets showed a significant linear
      correlation (R(2) = 0.996-0.998). Interparity and intraparity differences of the
      individual triplets' regression lines were also significantly different.
      CONCLUSIONS: The relationships support a model of two distinct growth periods for
      triplets: an age- and growth-promoting period until 33 weeks and an age-promoting
      growth-restricting period thereafter.

PMID- 12066125
TI  - Maternal and fetal inherited thrombophilias.

PMID- 12066126
TI  - Severe meconium aspiration syndrome.

PMID- 12066127
TI  - Severe brachial plexus injury in the posterior arm: An alternative explanation.

PMID- 12066128
TI  - Hippocrates and the dignity of human life.

PMID- 12066129
TI  - Is alternative medicine alternative science?

PMID- 12066130
TI  - The possible link between de-worming and the emergence of immunological disease.

PMID- 12066131
TI  - Personal and government regulation of nutritional supplements: what we want and
      what we should expect.

PMID- 12066132
TI  - Herbal medicines: poisons or potions?

PMID- 12066134
TI  - Evidence of increased formation of products retaining strong antioxidant activity
      from estradiol-17beta oxidation in the presence of human plasma lipoproteins.
AB  - Estradiol-17beta (E2) exhibits potent antioxidant effects that cause continuous
      suppression of metal-catalyzed oxidation of low-density-lipoprotein in vitro. We
      sought to learn whether unidentified oxidation products retaining strong
      antioxidant property may be generated from E2 incubated with lipoproteins and
      subjected to oxidation by reactive oxygen species generators. E2 oxidation was
      markedly stimulated in the presence of both LDL and high-density lipoprotein. We
      have isolated two novel products (less polar than E2), formed when E2 was
      oxidized with copper sulfate and hydrogen peroxide in the presence of
      lipoproteins). Both compounds had molecular weights of 306 on gas
      chromatography/mass spectrometry. They appear to be as strong as E2 in inhibiting
      LDL oxidation in vitro. Because of their increased hydrophobicity, they have the
      potential of being associated with LDL and offer promise as agents that can limit
      LDL oxidation, thereby contributing to cardioprotection.

PMID- 12066133
TI  - Antiphospholipid antibodies after surgical exposure to topical bovine thrombin.
AB  - Exposure to topical bovine thrombin during surgery frequently results in the
      development of antibodies to multiple protein and carbohydrate antigens. We
      investigated the frequency of increased levels of antibodies to cardiolipin and
      beta(2)-glycoprotein I (beta(2)-GPI) in two groups of patients, one exposed to
      bovine thrombin during cardiovascular surgery (n = 151) and a "control" group
      undergoing cardiovascular surgery but without exposure to bovine thrombin (n =
      11). Anticardiolipin antibody levels were increased before surgery in 10 of the
      151 patients exposed to topical thrombin (6.6%). Four to 8 weeks after surgery,
      84 patients (55.6%) had increased anticardiolipin antibody levels (P <.0001). In
      the control group, an increased anticardiolipin antibody level was present in a
      single patient before and after surgery (9%). Increased levels of antibodies to
      bovine and human beta(2)-GPI were also observed after surgery in the patients
      exposed to topical thrombin (37.7% and 38.2%, respectively). Increased
      anticardiolipin levels correlated with higher levels of antibody to bovine, but
      not human, beta(2)-GPI. In addition, increased levels of anticardiolipin antibody
      were associated with higher levels of antibodies to bovine factor V and
      prothrombin, as well as human factor V. Antibody binding on an enzyme-linked
      immunosorbent assay conducted to detect anticardiolipin antibody was dependent on
      the presence of anionic phospholipid, indicating that binding was not linked to
      the fetal bovine serum in the blocking buffer alone. Seven of 8 patients with
      delayed thromboembolic complications had increased anticardiolipin IgG antibody
      levels after surgery, but this association was not statistically significant.
      Nevertheless, our findings support the recommendation that the clinical safety of
      these commonly used hemostatic agents should be reassessed.

PMID- 12066135
TI  - Colchicine decreases apoptotic cell death in chronic cyclosporine nephrotoxicity.
AB  - Colchicine has been shown to prevent kidney injury in chronic cyclosporine
      nephrotoxicity; however, the mechanisms of its action are undetermined. The
      purpose of this study was to clarify whether colchicine prevents cyclosporine
      induced kidney injury by decreasing kidney-cell apoptosis. We also sought to
      determine whether such an antiapoptotic effect was related to Bcl-2/Bax protein
      and caspase3 activity. Adult male Sprague-Dawley rats kept on a salt-depleted
      diet (0.05% sodium) were treated daily for 28 days with cyclosporine (15 mg/kg in
      1 mL/kg olive-oil vehicle), colchicine (30 microg/kg in 100% ethanol, diluted
      with sterile saline solution to a final concentration of 30 microg/mL), or both
      cyclosporine and colchicine. Kidney function, histomorphologic findings, in situ
      terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate
      biotin nick end-labeling assay, expressions of Bcl-2 and Bax proteins, and
      caspase-3 enzymatic activity were compared for the different treatment groups.
      Compared with the vehicle-treated rats, rats given cyclosporine showed a decline
      in creatinine clearance rate, an increase in serum creatinine concentration,
      tubulointerstitial fibrosis, and an increase in the number of apoptotic cells
      (all P <.01). Concomitant administration of colchicine significantly reversed all
      the above parameters (all P <.05). The decreased expression of Bcl-2 and the
      ratio of Bcl-2 to Bax protein seen in cyclosporine-treated rat kidneys were
      significantly increased after colchicine treatment, accompanying a suppression of
      caspase-3 activity (P <.05). Furthermore, the decreased apoptotic cell death was
      closely correlated with improved renal tubulointerstitial fibrosis (r = 0.583, P
      <.05). These findings strongly suggest that a renoprotective effect of colchicine
      on cyclosporine-induced nephrotoxicity is coassociated with a decrease in
      apoptotic cells.

PMID- 12066138
TI  - Teaching science graduates to think business.

PMID- 12066136
TI  - Handling of low-density lipoprotein by the renal tubule: release of fragments due
      to incomplete degradation.
AB  - Because the mechanism by which lipoproteins are processed and modified in the
      renal tubule in patients with nephrosis is not completely understood, we studied
      the handling of low-density lipoprotein (LDL) in perfused rat kidneys made
      permeable by protamine. Protamine pretreatment increased the clearance of 125(I)
      LDL 25-fold compared to controls, thereby simulating a proteinuric kidney.
      Similar studies were also conducted in kidneys of rats made proteinuric by the
      induction of passive Heymann nephritis. Of the perfused iodinated LDL, 5% was
      localized in the cortex and lesser amounts in the medulla and urine. In the
      cortex and medulla, iodinated LDL was present mainly in the intact form (90%);
      just 10% was present in the degraded form. Using horseradish peroxidase
      conjugated to LDL, we demonstrated specific staining in the proximal tubules,
      suggesting that specific LDL receptors were present in that location. Although
      LDL in the tissue was present mostly in the intact form, it was 95% degraded in
      urine, and the degradation was inhibited by chloroquine, indicating that the
      lysosomes were the site of LDL metabolism. Gel chromatography and electrophoresis
      of iodinated LDL in the urine showed the presence of fragments in the range of 5
      to 15 kD. We conclude that renal degradation of LDL is incomplete and that the
      incompletely degraded fragments released into the urine may be toxic to the
      kidney by virtue of their lipid side-chains.

PMID- 12066139
TI  - Pay or train to publish?

PMID- 12066140
TI  - Distasteful but necessary.

PMID- 12066143
TI  - US set to rejoin international fusion project.

PMID- 12066141
TI  - Homeland security plan sparks fears for fight against bioterror.

PMID- 12066144
TI  - Statistical error leaves pollution data up in the air.

PMID- 12066145
TI  - France wires up to treat obsessive disorder.

PMID- 12066146
TI  - Science centres struggle as funds run out.

PMID- 12066148
TI  - Argentine crisis rattles cosmic-ray hunters.

PMID- 12066150
TI  - Bush asked for $200 million more for global disease fund.

PMID- 12066152
TI  - Plugging the brain drain.

PMID- 12066153
TI  - The great primate debate.

PMID- 12066154
TI  - Data security is crucial for Japanese science.

PMID- 12066155
TI  - Collaboration can work if inequality is recognized.

PMID- 12066156
TI  - Scientific links support an unjust peace process.

PMID- 12066157
TI  - In support of scientific exchange.

PMID- 12066158
TI  - Violence versus freedom.

PMID- 12066159
TI  - Did an academic boycott help to end apartheid?

PMID- 12066165
TI  - Health is wealth.

PMID- 12066166
TI  - Rocks that go bump in the night.

PMID- 12066167
TI  - Ecology: density and diversity.

PMID- 12066169
TI  - Electronics and the single atom.

PMID- 12066168
TI  - Cardiovascular biology: a cholesterol tether.

PMID- 12066170
TI  - The attraction of lipids.

PMID- 12066175
TI  - Solving the puzzle of mirror-image flowers.
AB  - Enantiostyly is a plant sexual polymorphism in which female sex organs are
      deflected to the left or right -- resulting in 'mirror-image' flowers -- but,
      although it occurs in at least a dozen unrelated families of flowering plants,
      its adaptive significance has been unclear. Here we show that a mendelian locus
      governs the inheritance of style orientation and that this curious form of sexual
      asymmetry functions to promote cross-pollination in bee-pollinated plants.

PMID- 12066171
TI  - Haemoglobin's chaperone.

PMID- 12066176
TI  - The value of bees to the coffee harvest.
AB  - The self-pollinating African shrub Coffea arabica, a pillar of tropical
      agriculture, was considered to gain nothing from insect pollinators. But I show
      here that naturalized, non-native honeybees can augment pollination and boost
      crop yields by over 50%. These findings, together with world coffee-harvest
      statistics and results from field studies of organically shade-grown coffee,
      indicate that coffee plants would benefit from being grown in habitats that are
      suitable for sustaining valuable pollinators.

PMID- 12066177
TI  - Architecture for a large-scale ion-trap quantum computer.
AB  - Among the numerous types of architecture being explored for quantum computers are
      systems utilizing ion traps, in which quantum bits (qubits) are formed from the
      electronic states of trapped ions and coupled through the Coulomb interaction.
      Although the elementary requirements for quantum computation have been
      demonstrated in this system, there exist theoretical and technical obstacles to
      scaling up the approach to large numbers of qubits. Therefore, recent efforts
      have been concentrated on using quantum communication to link a number of small
      ion-trap quantum systems. Developing the array-based approach, we show how to
      achieve massively parallel gate operation in a large-scale quantum computer,
      based on techniques already demonstrated for manipulating small quantum
      registers. The use of decoherence-free subspaces significantly reduces
      decoherence during ion transport, and removes the requirement of clock
      synchronization between the interaction regions.

PMID- 12066178
TI  - The recent breakup of an asteroid in the main-belt region.
AB  - The present population of asteroids in the main belt is largely the result of
      many past collisions. Ideally, the asteroid fragments resulting from each impact
      event could help us understand the large-scale collisions that shaped the planets
      during early epochs. Most known asteroid fragment families, however, are very old
      and have therefore undergone significant collisional and dynamical evolution
      since their formation. This evolution has masked the properties of the original
      collisions. Here we report the discovery of a family of asteroids that formed in
      a disruption event only 5.8 +/- 0.2 million years ago, and which has subsequently
      undergone little dynamical and collisional evolution. We identified 39 fragments,
      two of which are large and comparable in size (diameters of approximately 19 and
      approximately 14 km), with the remainder exhibiting a continuum of sizes in the
      range 2-7 km. The low measured ejection velocities suggest that gravitational re
      accumulation after a collision may be a common feature of asteroid evolution.
      Moreover, these data can be used to check numerical models of larger-scale
      collisions.

PMID- 12066179
TI  - Coulomb blockade and the Kondo effect in single-atom transistors.
AB  - Using molecules as electronic components is a powerful new direction in the
      science and technology of nanometre-scale systems. Experiments to date have
      examined a multitude of molecules conducting in parallel, or, in some cases,
      transport through single molecules. The latter includes molecules probed in a two
      terminal geometry using mechanically controlled break junctions or scanning
      probes as well as three-terminal single-molecule transistors made from carbon
      nanotubes, C(60) molecules, and conjugated molecules diluted in a less-conducting
      molecular layer. The ultimate limit would be a device where electrons hop on to,
      and off from, a single atom between two contacts. Here we describe transistors
      incorporating a transition-metal complex designed so that electron transport
      occurs through well-defined charge states of a single atom. We examine two
      related molecules containing a Co ion bonded to polypyridyl ligands, attached to
      insulating tethers of different lengths. Changing the length of the insulating
      tether alters the coupling of the ion to the electrodes, enabling the fabrication
      of devices that exhibit either single-electron phenomena, such as Coulomb
      blockade, or the Kondo effect.

PMID- 12066180
TI  - Kondo resonance in a single-molecule transistor.
AB  - When an individual molecule, nanocrystal, nanotube or lithographically defined
      quantum dot is attached to metallic electrodes via tunnel barriers, electron
      transport is dominated by single-electron charging and energy-level quantization.
      As the coupling to the electrodes increases, higher-order tunnelling and
      correlated electron motion give rise to new phenomena, including the Kondo
      resonance. To date, all of the studies of Kondo phenomena in quantum dots have
      been performed on systems where precise control over the spin degrees of freedom
      is difficult. Molecules incorporating transition-metal atoms provide powerful new
      systems in this regard, because the spin and orbital degrees of freedom can be
      controlled through well-defined chemistry. Here we report the observation of the
      Kondo effect in single-molecule transistors, where an individual divanadium
      molecule serves as a spin impurity. We find that the Kondo resonance can be tuned
      reversibly using the gate voltage to alter the charge and spin state of the
      molecule. The resonance persists at temperatures up to 30 K and when the energy
      separation between the molecular state and the Fermi level of the metal exceeds
      100 meV.

PMID- 12066181
TI  - Mycorrhizal weathering of apatite as an important calcium source in base-poor
      forest ecosystems.
AB  - The depletion of calcium in forest ecosystems of the northeastern USA is thought
      to be a consequence of acidic deposition and to be at present restricting the
      recovery of forest and aquatic systems now that acidic deposition itself is
      declining. This depletion of calcium has been inferred from studies showing that
      sources of calcium in forest ecosystems namely, atmospheric deposition and
      mineral weathering of silicate rocks such as plagioclase, a calcium-sodium
      silicate do not match calcium outputs observed in forest streams. It is therefore
      thought that calcium is being lost from exchangeable and organically bound
      calcium in forest soils. Here we investigate the sources of calcium in the
      Hubbard Brook experimental forest, through analysis of calcium and strontium
      abundances and strontium isotope ratios within various soil, vegetation and
      hydrological pools. We show that the dissolution of apatite (calcium phosphate)
      represents a source of calcium that is comparable in size to known inputs from
      atmospheric sources and silicate weathering. Moreover, apatite-derived calcium
      was utilized largely by ectomycorrhizal tree species, suggesting that mycorrhizae
      may weather apatite and absorb the released ions directly, without the ions
      entering the exchangeable soil pool. Therefore, it seems that apatite weathering
      can compensate for some of the calcium lost from base-poor ecosystems, and should
      be considered when estimating soil acidification impacts and calcium cycling.

PMID- 12066182
TI  - Density-dependent mortality and the latitudinal gradient in species diversity.
AB  - Ecologists have long postulated that density-dependent mortality maintains high
      tree diversity in the tropics. If species experience greater mortality when
      abundant, then more rare species can persist. Agents of density-dependent
      mortality (such as host-specific predators, and pathogens) may be more prevalent
      or have stronger effects in tropical forests, because they are not limited by
      climatic factors. If so, decreasing density-dependent mortality with increasing
      latitude could partially explain the observed latitudinal gradient in tree
      diversity. This hypothesis has never been tested with latitudinal data. Here we
      show that several temperate tree species experience density-dependent mortality
      between seed dispersal and seedling establishment. The proportion of species
      affected is equivalent to that in tropical forests, failing to support the
      hypothesis that this mechanism is more prevalent at tropical latitudes. We
      further show that density-dependent mortality is misinterpreted in previous
      studies. Our results and evidence from other studies suggest that density
      dependent mortality is important in many forests. Thus, unless the strength of
      density-dependent mortality varies with latitude, this mechanism is not likely to
      explain the high diversity of tropical forests.

PMID- 12066183
TI  - Geographic structure and dynamics of coevolutionary selection.
AB  - Coevolution of species is one of the major processes organizing the Earth's
      biodiversity. Recent coevolutionary theory has indicated that the geographic
      structure of species has the potential to impose powerful and continuing effects
      on coevolutionary dynamics, if that structure creates selection mosaics and
      coevolutionary hotspots across landscapes. Here we confirm that current
      coevolutionary selection in interspecific interactions can be highly divergent
      across both narrow and broad geographic scales, thereby fueling continuing
      coevolution of taxa. Study of a widespread plant insect interaction across a
      broad range of habitats for several years showed that an insect functioning both
      as a pollinator and a floral parasite can be strongly mutualistic in some
      habitats but commensal or antagonistic in neighbouring habitats. The results for
      one of the habitats span seven years, demonstrating that the local structure of
      coevolutionary selection can remain stable across multiple generations.
      Conservation of the evolutionary processes maintaining long-term biological
      diversity may require preservation of the conditions that allow a long-term
      shifting geographic mosaic of coevolutionary hotspots and coldspots.

PMID- 12066184
TI  - Spike train dynamics predicts theta-related phase precession in hippocampal
      pyramidal cells.
AB  - According to the temporal coding hypothesis, neurons encode information by the
      exact timing of spikes. An example of temporal coding is the hippocampal phase
      precession phenomenon, in which the timing of pyramidal cell spikes relative to
      the theta rhythm shows a unidirectional forward precession during spatial
      behaviour. Here we show that phase precession occurs in both spatial and non
      spatial behaviours. We found that spike phase correlated with instantaneous
      discharge rate, and processed unidirectionally at high rates, regardless of
      behaviour. The spatial phase precession phenomenon is therefore a manifestation
      of a more fundamental principle governing the timing of pyramidal cell discharge.
      We suggest that intrinsic properties of pyramidal cells have a key role in
      determining spike times, and that the interplay between the magnitude of
      dendritic excitation and rhythmic inhibition of the somatic region is responsible
      for the phase assignment of spikes.

PMID- 12066185
TI  - Role of experience and oscillations in transforming a rate code into a temporal
      code.
AB  - In the vast majority of brain areas, the firing rates of neurons, averaged over
      several hundred milliseconds to several seconds, can be strongly modulated by,
      and provide accurate information about, properties of their inputs. This is
      referred to as the rate code. However, the biophysical laws of synaptic
      plasticity require precise timing of spikes over short timescales (<10 ms). Hence
      it is critical to understand the physiological mechanisms that can generate
      precise spike timing in vivo, and the relationship between such a temporal code
      and a rate code. Here we propose a mechanism by which a temporal code can be
      generated through an interaction between an asymmetric rate code and oscillatory
      inhibition. Consistent with the predictions of our model, the rate and temporal
      codes of hippocampal pyramidal neurons are highly correlated. Furthermore, the
      temporal code becomes more robust with experience. The resulting spike timing
      satisfies the temporal order constraints of hebbian learning. Thus, oscillations
      and receptive field asymmetry may have a critical role in temporal sequence
      learning.

PMID- 12066186
TI  - Modulation of virulence within a pathogenicity island in vancomycin-resistant
      Enterococcus faecalis.
AB  - Enterococci are members of the healthy human intestinal flora, but are also
      leading causes of highly antibiotic-resistant, hospital-acquired infection. We
      examined the genomes of a strain of Enterococcus faecalis that caused an
      infectious outbreak in a hospital ward in the mid-1980s (ref. 2), and a strain
      that was identified as the first vancomycin-resistant isolate in the United
      States, and found that virulence determinants were clustered on a large
      pathogenicity island, a genetic element previously unknown in this genus. The
      pathogenicity island, which varies only subtly between strains, is approximately
      150 kilobases in size, has a lower G + C content than the rest of the genome, and
      is flanked by terminal repeats. Here we show that subtle variations within the
      structure of the pathogenicity island enable strains harbouring the element to
      modulate virulence, and that these variations occur at high frequency. Moreover,
      the enterococcal pathogenicity island, in addition to coding for most known
      auxiliary traits that enhance virulence of the organism, includes a number of
      additional, previously unstudied genes that are rare in non-infection-derived
      isolates, identifying a class of new targets associated with disease which are
      not essential for the commensal behaviour of the organism.

PMID- 12066187
TI  - Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.
AB  - Complications of atherosclerosis are the most common cause of death in Western
      societies. Among the many risk factors identified by epidemiological studies,
      only elevated levels of lipoproteins containing apolipoprotein (apo) B can drive
      the development of atherosclerosis in humans and experimental animals even in the
      absence of other risk factors. However, the mechanisms that lead to
      atherosclerosis are still poorly understood. We tested the hypothesis that the
      subendothelial retention of atherogenic apoB-containing lipoproteins is the
      initiating event in atherogenesis. The extracellular matrix of the
      subendothelium, particularly proteoglycans, is thought to play a major role in
      the retention of atherogenic lipoproteins. The interaction between atherogenic
      lipoproteins and proteoglycans involves an ionic interaction between basic amino
      acids in apoB100 and negatively charged sulphate groups on the proteoglycans.
      Here we present direct experimental evidence that the atherogenicity of apoB
      containing low-density lipoproteins (LDL) is linked to their affinity for artery
      wall proteoglycans. Mice expressing proteoglycan-binding-defective LDL developed
      significantly less atherosclerosis than mice expressing wild-type control LDL. We
      conclude that subendothelial retention of apoB100-containing lipoprotein is an
      early step in atherogenesis.

PMID- 12066188
TI  - T-box gene tbx5 is essential for formation of the pectoral limb bud.
AB  - The T-box genes Tbx4 and Tbx5 have been shown to have key functions in the
      specification of the identity of the vertebrate forelimb (Tbx5) and hindlimb
      (Tbx4). Here we show that in zebrafish, Tbx5 has an additional early function
      that precedes the formation of the limb bud itself. Functional knockdown of
      zebrafish tbx5 through the use of an antisense oligonucleotide resulted in a
      failure to initiate fin bud formation, leading to the complete loss of pectoral
      fins. The function of the tbx5 gene in the development of zebrafish forelimbs
      seems to involve the directed migration of individual lateral-plate mesodermal
      cells into the future limb-bud-producing region. The primary defect seen in the
      tbx5-knockdown phenotype is similar to the primary defects described in known T
      box-gene mutants such as the spadetail mutant of zebrafish and the Brachyury
      mutant of the mouse, which both similarly exhibit an altered migration of
      mesodermal cells. A common function for many of the T-box genes might therefore
      be in mediating the proper migration and/or changes in adhesive properties of
      early embryonic cells.

PMID- 12066189
TI  - An abundant erythroid protein that stabilizes free alpha-haemoglobin.
AB  - The development of red blood cells (erythrocytes) is distinguished by high-level
      production of the oxygen carrier, haemoglobin A (HbA), a heterotetramer of alpha-
      and beta-haemoglobin subunits. HbA synthesis is coordinated to minimize the
      accumulation of free subunits that form cytotoxic precipitates. Molecular
      chaperones that regulate globin subunit stability, folding or assembly have been
      proposed to exist but have never been identified. Here we identify a protein
      stabilizing free alpha-haemoglobin by using a screen for genes induced by the
      essential erythroid transcription factor GATA-1 (refs 4, 5). Alpha Haemoglobin
      Stabilizing Protein (AHSP) is an abundant, erythroid-specific protein that forms
      a stable complex with free alpha-haemoglobin but not with beta-haemoglobin or
      haemoglobin A (alpha(2)beta(2)). Moreover, AHSP specifically protects free alpha
      haemoglobin from precipitation in solution and in live cells. AHSP-gene-ablated
      mice exhibit reticulocytosis and abnormal erythrocyte morphology with
      intracellular inclusion bodies that stain positively for denatured haemoglobins.
      Hence, AHSP is required for normal erythropoiesis, probably acting to block the
      deleterious effects of free alpha-haemoglobin precipitation. Accordingly, AHSP
      gene dosage is predicted to modulate pathological states of alpha-haemoglobin
      excess, such as beta-thalassaemia.

PMID- 12066192
TI  - Changes in blood-brain barrier permeability induced by radiotherapy: implications
      for timing of chemotherapy? (Review).
AB  - The brain requires a stable internal environment, which is established by the
      integrity of the blood-brain barrier (BBB). The efficacy of chemotherapeutics in
      the treatment of brain malignancies is often hampered by the presence of the BBB.
      BBB disruption can be performed either by osmotic disruption, bradykinin or
      irradiation. Radiotherapy with doses of 20 to 30 Gy with fraction size of 2 Gy
      may be used to increase the permeability of the BBB. These radiation doses by
      themselves will not give rise to serious side effects or long-term complications.
      Disruption of the BBB by radiotherapy might have implications in the treatment of
      primary brain tumors, cerebral metastases, and prophylactic cranial irradiation
      in small cell lung cancer since irradiation will cause cell kill and may enhance
      the effect of chemotherapy. We present a review on the effects of irradiation on
      the BBB and subsequently discuss the potential value for therapeutic
      applications.

PMID- 12066190
TI  - Regulation of Arabidopsis cryptochrome 2 by blue-light-dependent phosphorylation.
AB  - Cryptochromes are blue/ultraviolet-A light receptors that mediate various light
      responses in plants and animals. But the initial photochemical reaction of
      cryptochrome is still unclear. For example, although most photoreceptors are
      known to undergo light-dependent protein modification such as phosphorylation, no
      blue-light dependent phosphorylation has been reported for a cryptochrome.
      Arabidopsis cryptochrome 2 (cry2) mediates light regulation of seedling
      development and photoperiodic flowering. The physiological activity and cellular
      level of cry2 protein are light-dependent, and protein protein interactions are
      important for cry2 function. Here we report that cry2 undergoes a blue-light
      dependent phosphorylation, and that cry2 phosphorylation is associated with its
      function and regulation. Our results suggest that, in the absence of light, cry2
      remains unphosphorylated, inactive and stable; absorption of blue light induces
      the phosphorylation of cry2, triggering photomorphogenic responses and eventually
      degradation of the photoreceptor.

PMID- 12066193
TI  - Assessment of Glut-1 expression in cholangiocarcinoma, benign biliary lesions and
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC), cholangiocarcinoma (Chca) and benign bile ductule
      proliferations represent uncommon but important differential diagnoses in liver
      masses, especially if the patient has no known primary malignancy. The glucose
      transporter protein Glut-1 is commonly expressed in adenocarcinomas but its
      expression in HCC, Chca, and benign bile ductules has not been systematically
      investigated. Forty-two cases of Chca, 27 cases of benign bile ductule
      proliferations and 19 cases of HCC were stained with Glut-1. Cases were evaluated
      for a membranous staining pattern in tumor cells and the results compared. Twenty
      one of 42 (50%) Chca stained with Glut-1 while no HCC or benign bile ductule
      proliferations did, neither did benign hepatocytes or portal triad structures.
      Glut-1 is a highly specific but insensitive stain for Chca. It may prove to be a
      helpful part of a diagnostic panel used to evaluate liver lesions.

PMID- 12066194
TI  - Chemoprevention of lung cancer by non-steroidal anti-inflammatory drugs among
      cigarette smokers.
AB  - We conducted an epidemiologic case control study of NSAIDs among 489 lung cancer
      patients and 978 control subjects. The case patients were diagnosed and treated
      during 1996-1999 at the James Cancer Hospital and Research Institute, Columbus,
      OH. Each lung cancer diagnosis was verified by examination of the pathology
      report. Population controls free of disease were obtained from health screening
      clinics and frequency-matched to the cases at a 2:1 rate. Matching
      characteristics included age, gender, and pack-years of cigarette smoking. In
      order to assess the effects of NSAIDs on tobacco carcinogenesis, only heavy
      smokers were included in the control group. Information on the use of aspirin,
      ibuprofen, and prescription NSAIDs was obtained by personal interviews. Effects
      of NSAIDs on lung cancer risk were assessed by estimating odds ratios (relative
      risks) with 95% confidence intervals and performing trend tests. Daily intake of
      NSAIDs for at least 2 years prior to interview was associated with a 68%
      reduction in the relative risk of lung cancer (RR, 0.32; 95% CI, 0.23-0.44;
      p<0.01). The inverse trend of lung cancer risk with increasing NSAID use was
      highly significant (p<0.01). Results were similar for men (RR, 0.41) and women
      (RR, 0.22), and for the individual compounds, aspirin (RR, 0.25) and ibuprofen
      (RR, 0.39). These results combined with the current molecular evidence suggest
      that regular NSAID intake may prevent tobacco carcinogenesis through COX-2
      blockade.

PMID- 12066195
TI  - Differentiation of positive autofluorescence bronchoscopy findings by comparative
      genomic hybridization.
AB  - Up to 50% of the results of autofluorescence bronchoscopy (AF) of histologically
      benign lesions are false-positive. For better differentiation of such lesions we
      have used comparative genomic hybridization (CGH). We studied biopsy material
      from 47 patients by CGH. For a comparison of findings, the patients were grouped
      as follows: Group 1, patients with manifest malignant lesions (n=10); group 2,
      patients with positive autofluorescence and negative (benign) histology (n=16);
      group 3, patients with negative autofluorescence and negative histology, who
      belong to a typical high-risk group for lung cancer (n=21). The biopsy specimens
      of 21/47 patients (45%) showed chromosome aberrations. In 8/10 cases (80%) in
      group 1, one or several chromosome lesions were detected. Chromosome aberrations
      were found in 13/16 specimens (81%) taken in group 2. None of the 21 biopsy
      specimens from the patients of group 3 showed any chromosome lesions. The
      chromosome aberrations detected in groups 1 and 2 show nearly identical
      distribution patterns. Lesions of chromosome 3 are the most frequent ones in both
      groups. The results of the CGH investigation show that regions of the bronchial
      mucosa with positive AF finding and benign histology frequently are seriously
      damaged and may develop into potentially malignant lesions.

PMID- 12066196
TI  - Prognostic relevance of p53 protein expression in glioblastoma.
AB  - TP53 plays a key role in cellular response to DNA-damaging agents, and mutation
      of this gene, which is associated with immunohistochemically detectable p53
      protein accumulation, may influence response to chemo- and radiotherapy. We
      investigated immunohistochemically the influence of p53 protein accumulation in
      114 consecutive cases of primary glioblastoma treated by surgery and adjuvant
      radio- and chemotherapy. In addition, we determined cellular proliferation index
      using the antibody MIB-1 and apoptotic index of tumor cells using the TUNEL
      assay. Twenty-nine patients (25.4%) were considered as positive with regard to
      p53 protein expression (>50% p53 immunostained tumor cells). Patients with p53
      positive glioblastomas were significantly younger (mean age 54.4+/-2 years) than
      those with p53 negative tumors (mean age 61.4+/-1.1 years) (p=0.002, Mann-Whitney
      test). While no significant difference in apoptotic index was found, we observed
      a significantly higher MIB-1 labeling index (LI) in patients with p53 positive
      tumors (median LI: 36.4%) compared to p53 negative ones (median LI: 23.8%)
      (p=0.005, Mann-Whitney test). p53 protein expression was associated with
      significantly longer survival in univariate analysis (p=0.0399, log-rank test).
      In multivariate analysis of overall survival (Cox regression) only postoperative
      Karnofsky performance status remained as independent prognostic factor. We
      conclude that glioblastoma patients with immunohistochemically detectable p53
      protein expression, who received adjuvant radio- and chemotherapy, have a
      significantly better overall survival, possibly due to increased sensitivity to
      this adjuvant treatment.

PMID- 12066197
TI  - Nijmegen breakage syndrome gene (NBS1) is not the tumor suppressor gene at 8q21.3
      involved in colorectal carcinoma.
AB  - Genetic instability is characteristic of cancer cells, both at the chromosomal
      level (e.g., aneuploidy, aneusomy, translocations), and at the sequence level
      (e.g., microsatellite instability). Colorectal cancers (CRCs) can be divided into
      two groups: tumors of the proximal colon, where microsatellite instability is
      frequent and chromosomal aberrations are rare, and tumors of the distal colon,
      where microsatellite instability is less frequent and chromosomal aberrations are
      common. Constitutional chromosomal instability is a hallmark of the Nijmegen
      breakage syndrome (NBS), a disorder in which the NBS1 gene is mutated. In a
      previous study, we found an elevated frequency of allelic imbalance (AI) at the
      8q21.3 NBS1 locus in proximal, though not distal CRCs. This result suggested that
      the loss of NBS1 might contribute to the genetic instability, and thus the
      malignant progression, of proximal CRC. We therefore sequenced the 16 exons of
      the NBS1 gene in all cases where we had observed AI. Of the 29 cases, none showed
      any sequence anomaly, although several polymorphisms were found. We also studied
      markers flanking the recently described Rad54B gene, which is a member of the
      Rad52 epistasis group to which NBS1 itself belongs. Mutations of this gene,
      located a few cM distal to NBS1, have been found in colorectal cancer and in
      primary lymphomas, and it may thus be the target of AI at 8q21. We found that AI
      at Rad54B was not frequent, and none was observed in cases showing AI at NBS1.

PMID- 12066198
TI  - Successive cultures of mature hepatocytes for hepatocyte autotransplantation to
      assist liver function after liver resection for cancer.
AB  - We developed a method for the rapid successive cultures of adult rat mature
      hepatocytes on plastic dishes while avoiding viral transformation or co-culture
      with other cell lines. This method also allows for culturing adult human mature
      hepatocytes up to the secondary culture. These can be expected to provide a good
      source for hepatocyte autotransplantation, and, combined with the previously
      reported methods for the transplantation of hepatocytes into the spleen, a
      promising option for the support of liver function after liver resection for
      cancer without the need for immunosuppressive agents.

PMID- 12066199
TI  - Up-regulated gene expression of angiogenesis factors in post-chemotherapeutic
      lung cancer tissues determined by cDNA macroarray.
AB  - The differential expressions of hundreds of tightly transcriptionally controlled
      genes in freshly isolated human lung cancers and respective normal lung tissues
      were analyzed by the cDNA macroarray technique. Three lung cancer patients
      received pre-operative chemotherapy with cisplatin containing regimens. After
      chemotherapy, these patients underwent surgery, and poly (A)-RNA expressions of
      588 genes in the samples prepared from the lung cancer and normal lung tissues
      were compared. These expressions of the 588 genes were demonstrated by spotting
      onto a filter. Histogram analysis of gene expression revealed the tumors to show
      commonly up-regulated expression of angiogenesis and invasion related genes and
      adhesion molecules such as fibroblast growth factor 3 (FGFR3), matrix
      metalloproteinase (MMP)15, 16 and 10, integrin beta 4, integrin alpha 9,
      endonexin, and several types of collagens. Thus, post-chemotherapeutic tissues
      from lung cancer parents are characterized by remarkable up-regulation of
      molecules related to angiogenesis, invasion and adhesion. Tree view showed close
      clustering of angiogenesis related genes. Furthermore, when the angiogenesis
      related genes were selected and clustered, they were categorized into three
      groups depending upon gene expression profiles. These results suggest that
      angiogenesis related molecules are suitable candidates for target-based
      therapeutics and angiogenesis inhibitors are expected to be effective in lung
      cancer patients pretreated with chemotherapy.

PMID- 12066201
TI  - Morphologic approach to hepatocellular carcinoma development in man: de novo or
      the so-called 'dysplastic nodule-carcinoma' sequence?
AB  - The so-called dysplastic nodule-carcinoma sequence in the liver is generally
      accepted because hepatocellular carcinoma is not an uncommon finding in
      precancerous lesions. In order to evaluate the existence and frequency of de novo
      hepatocarcinogenesis we studied 112 surgically resected early well-differentiated
      hepatocellular carcinomas showing replacing growth without less differentiated
      component in themselves. They were divided into two groups: carcinoma in
      dysplastic area (type A) and carcinoma without dysplastic area (type B) and were
      analyzed clinicopathologically. We encountered 77 cases of type A (68.8%) and 35
      of type B (31.2%). The frequency of type A in cirrhotic group (74.7%) is
      statistically higher than that of non-cirrhotic group (54.5%) (p=0.0453). Using
      multivariate analysis, the occurrence of type A was related with higher age, the
      presence of cirrhosis and hepatitis B surface antigen positive. The tumor size
      and the presence of fatty change in the tumor tended to relate with type A. We
      propose two pathways morphologically in early hepatocarcinogenesis, one of which
      has a close relation to hepatitis B virus and/or cirrhosis.

PMID- 12066200
TI  - Expression of p73 gene, cell proliferation and apoptosis in breast cancer:
      Immunohistochemical and clinicopathological study.
AB  - p73 is a member of p53 tumor suppressor protein family. In spite of similarities
      of three meaningful domains between p53 and p73, the exact function of p73
      protein is not established. To approach the relevance of p73 expression to a
      pathological parameter in human breast cancer, the apoptotic index (AI) and the
      mitotic index (MI) were examined for 75 patients with the breast cancer after
      mastectomies. We found that both of the AI and MI in p73-positive cases were
      significantly higher compared to the p73-negative cases, suggesting that the p73
      positive cases in the breast cancer were in advanced grade. In six cases of
      breast cancer with distant metastasis, however, the p73 expression was slight and
      showing low AI but high MI. Advanced breast cancer with distant metastasis seemed
      to lose the p73 expression and gain the function of evading apoptosis.
      Altogether, these data demonstrate that p73 expression is well correlated with AI
      in breast cancer.

PMID- 12066202
TI  - Participation of alpha-smooth muscle actin-positive cells in renomedullary
      interstitial cell tumors.
AB  - Renomedullary interstitial cell tumors are benign lesions which are generally
      discovered in specimens nephrectomized for other malignant tumors or by autopsy.
      We examined the histologic features of eight tumors from four patients and
      investigated the appearance of alpha-smooth muscle actin (ASMA)-positive cells in
      these tumors using immunohistochemistry. We considered that five tumors are
      cellular type and the remaining three as fibrous. Characteristic hyalinization
      was observed in two of the three fibrous tumors. All the tumors except for one
      fibrous type contained entrapped tubular cells. CD35-positive cells (dendritic
      cells) and ASMA-positive cells were observed in all the tumors, with a more
      frequent occurrence in the cellular type than the fibrous type. CD35-negative
      spindle cells were considered as fibroblasts or activated fibroblasts
      (myofibroblasts). The number of CD35-positive cells was higher than that of ASMA
      positive cells. Additionally, the entrapped tubular cells showed the transition
      to spindle cells and some of them expressed for ASMA. With double
      immunohistochemical staining, there were some cells showing positive reactions
      for both CD35 and ASMA. Furthermore, an ultrastructural examination confirmed the
      presence of ASMA-positive filaments in the dendritic cells and myofibroblasts.
      The expression of TGF-beta 1 was observed not only in the tumor cells and the
      collecting ducts surrounding the tumor but also in the entrapped tubular cells.
      In addition, the intensity of TGF-beta 1 was stronger in/around the tumor than in
      the areas distant from the tumor. The positive cells were more numerous in the
      cellular type than in the fibrous type. In conclusion, ASMA-positive cells appear
      in renomedullary interstitial cell tumors and some of the cells may originate in
      dendritic interstitial cells, fibroblasts including myofibroblasts, and entrapped
      tubular cells. Furthermore, TGF-beta 1 may contribute to the formation of
      fibrosis in the tumors.

PMID- 12066203
TI  - Association of matrilysin expression with progression and poor prognosis in human
      pancreatic adenocarcinoma.
AB  - The matrix metalloproteinase matrilysin has been implicated in the progression of
      gastrointestinal and other cancers. The aim of this study was to determine
      whether matrilysin has clinicopathological and prognostic significance in
      pancreatic carcinoma. Using immunohistochemistry, we analyzed 39 pancreatic
      adenocarcinoma tissues for expression of matrilysin. The results were matched
      with clinicopathological characteristics and patient survival. The relationship
      of matrilysin expression with p53 expression or cellular proliferation determined
      by Ki-67 expression was also investigated. Sections with immunostaining signals
      in more than 30% of carcinoma cells at the invasive front, which were observed in
      25 (64%) cases, were judged to be positive for matrilysin. Matrilysin positivity
      was significantly correlated with infiltrating growth pattern, lymph node
      metastasis, and postoperative recurrence. Expression of matrilysin was not
      correlated with either Ki-67 or p53 expression. Patients with matrilysin-positive
      carcinoma had a significantly shorter overall survival time than did those with
      matrilysin-negative carcinoma. Our results suggest that matrilysin plays a key
      role in the progression of pancreatic carcinoma.

PMID- 12066204
TI  - Specific induction of apoptosis by 1,8-cineole in two human leukemia cell lines,
      but not a in human stomach cancer cell line.
AB  - We have investigated the effects of 1,8-cineole [the main component of essential
      oil prepared from bay-leaves Laurus nobilis L.)] on DNA of human leukemia cell
      lines, Molt 4B, HL-60 and stomach cancer KATO III cells. Specific induction of
      apoptosis by 1,8-cineole was observed in human leukemia Molt 4B and HL-60 cells,
      but not in human stomach cancer KATO III cells. Morphological changes showing
      apoptotic bodies were observed in the human leukemia HL-60 cells treated with 1,8
      cineole. The fragmentations of DNA by cineole to oligonucleosomal-sized fragments
      that is a characteristic of apoptosis were concentration- and time-dependent in
      Molt 4B and HL-60 cells, but not in KATO III cells. The present study shows that
      the suppression growth by 1,8-cineole in the leukemia cell lines results from the
      induction of apoptosis by this compound.

PMID- 12066205
TI  - Expression of cyclooxygenase-2 and vascular endothelial growth factor in
      pancreatic tumors.
AB  - Cyclooxygenase (COX)-2 and vascular endothelial growth factor (VEGF) have been
      reported to be significantly related to carcinogenesis or progression of various
      cancers. However, there has been no report on the relation between COX-2 and VEGF
      overexpression in pancreatic tumors. We investigated the overexpression of COX-2
      and VEGF immunohistochemically in intraductal papillary-mucinous tumors (IPMT)
      and invasive ductal carcinoma (IDC) and examined the relationship with
      clinicopathological factors and the correlation between these immunoactivities in
      IPMT and IDC. In IPMT, the positive rates of COX-2 overexpression were 0% in 10
      areas of hyperplasia, 54.5% of adenoma, 83.3% of intraductal areas of
      adenocarcinoma, and 66.7% of invasive areas of adenocarcinoma. On the contrary,
      47.8% of IDC were positive for COX-2 overexpression. The positive rates of VEGF
      in IPMT were 10% in areas of hyperplasia, 54.5% of adenoma, 66.7% of intraductal
      areas of adenocarcinoma and 66.7% of invasive areas of adenocarcinoma. However,
      in IDC it was 47.8%. Only lymph node metastasis correlated significantly with
      VEGF overexpression (p=0.04), while the other factors had no significant
      relationships with either COX-2 or VEGF overexpression. There was a statistically
      significant correlation between COX-2 and VEGF overexpression in IPMT (p<0.001),
      in 5 patients with adenoma of which both COX-2 and VEGF were stained in almost
      exactly the same locations. On the contrary, COX-2 and VEGF overexpression had no
      statistically significant relationship in IDC. In conclusion, we demonstrate
      evidence of COX-2 and VEGF overexpression in human pancreatic tumors.
      Chemoprevention via the suppression of angiogenesis by means of COX-2 inhibitor
      may be more effective in IPMT than in IDC, because of the strong correlation of
      both factors especially in IPMT.

PMID- 12066206
TI  - Late course accelerated hyperfractionation radiotherapy concomitant with
      cisplatin in patients with esophageal carcinoma.
AB  - The purpose of this study was to examine whether combined cisplatin and late
      course accelerated fractionation radiotherapy (LCAH) (the combined group) can
      confer a better outcome over LCAH alone in treating esophageal carcinoma. Eighty
      one eligible patients were randomly entered into two groups: the LCAH alone
      group, and the combined group. There was a better outcome in the combined group
      compared to the LCAH group, but the difference was not significant. The combined
      therapy could significantly improve the survival rate and local control of the
      disease in the early stage, but not in the advanced stage, because of the
      possibility of invasion. More severe complications occurred in the combined group
      than in the LCAH group, but they were within tolerance. In conclusion, LCAH
      concomitant with cisplatin could improve the survival of patients with esophageal
      cancer, especially in the early stage, as long as the side effects of the
      treatment are within tolerable limits.

PMID- 12066207
TI  - Oestrogen causes G2/M arrest and apoptosis in breast cancer cells MDA-MB-231.
AB  - Flavonoids have been shown to exert many biological activities within cancer
      cells, and oestrogen is known to be structurally related to flavonoids. We
      investigated the effects of oestrogen in cancer cells to determine if its
      activities would be similar to those of flavonoids. When 50 microM 17 beta
      oestradiol (oestradiol) was added to the oestrogen receptor (ER) alpha-negative
      breast cancer cell line MDA-MB-231, growth arrest was apparent, similar to that
      observed with genistein and daidzein. Oestradiol exhibited a dose response curve
      for the growth arrest similar to those of genistein and daidzein. Apoptosis
      occurred in the breast cancer cells after treatment with 50 microM oestradiol,
      genistein, or daidzein, with similar profiles. Flow cytometry analysis revealed
      that oestradiol treatment caused G2/M arrest and apoptosis. Cell-cycle arrest at
      G2/M began at 6 h after treatment, and apoptosis began within 24 h. Because MDA
      MB-231 cells are ER alpha negative, these results suggest that oestradiol induces
      cell-cycle arrest and apoptosis through an ER alpha-independent pathway.

PMID- 12066208
TI  - Docetaxel enhances the cytotoxicity of anthracyclines by increasing intracellular
      drug accumulation.
AB  - We assessed the combined antitumor activity of docetaxel and doxorubicin (DXR)
      and tetrahydropyranyl-adriamycin (THP) using the human breast carcinoma cell
      lines R-27 and MDA-MB-231. Synergistic antitumor activity was observed for both
      combined docetaxel and DXR, and docetaxel and THP against R-27 cells when
      contacted simultaneously. However, only additive effects were observed against
      MDA-MB-231 cells. Intracellular concentrations of DXR and THP in R-27 cells were
      significantly increased by docetaxel pretreatment, however, this increase was not
      observed in MDA-MB-231 cells, which exhibited only additive sensitivity to the
      treatment. Thus, docetaxel increased the antitumor activity of anthracyclines by
      increasing their intracellular concentrations.

PMID- 12066209
TI  - Outpatient therapy with irinotecan and low-dose cisplatin for metastatic
      colorectal cancer resistant to 5-fluorouracil.
AB  - Chemotherapy with irinotecan hydrochloride and low-dose cisplatin was tested for
      the treatment of metastatic colorectal cancer showing resistance to 5
      fluorouracil. Eleven consecutive patients with advanced metastatic colorectal
      cancer (performance status: 0 to 2), who had shown tumor progression on
      chemotherapy with 5-fluorouracil/leucovorin, were treated with irinotecan (60
      mg/m2) plus cisplatin (6 mg/m2) by 90-min intravenous infusion. Treatment was
      repeated weekly for 3 weeks during admission and then fortnightly on an
      outpatient basis. Objective responses were observed in four patients (36%; 95%
      confidence interval: 11%-69%). The median duration of response was 5.5 months and
      six patients are still alive. The time to disease progression was longer in the
      no change group (7.0+/-3.6 months: mean +/- SD) than in the responder group
      (5.5+/-1.9 months), and there was no difference of median survival between the
      two groups (10.0 versus 10.3 months). The overall median survival was 8.2 months
      (range: 4 to 12+ months). This treatment was well tolerated. Six patients
      experienced grade 1 or 2 leucopenia, while grade I diarrhea and nausea occurred
      in three and five patients, respectively. Based on the good response, excellent
      quality of life, and convenience, the present regimen seems to be reasonable
      second-line outpatient chemotherapy for patients with metastatic colorectal
      cancer showing resistance to 5-fluorouracil.

PMID- 12066210
TI  - Diagnosis of hepatocellular carcinoma using digital subtraction imaging with the
      contrast agent, Levovist: comparison with helical CT, digital subtraction
      angiography, and US angiography.
AB  - Digital subtraction imaging was compared to helical CT, DSA, and US angiography
      to assess its usefulness in the evaluation of vascularity in hepatocellular
      carcinoma (HCC). Digital subtraction imaging using Levovist as the contrast agent
      was performed in 41 patients with 43 nodules (22 men and 19 women, aged 50 to 83
      years; mean age, 65 years; mean maximum tumor diameter, 27.8+/-17.1 mm). Digital
      subtraction imaging showed hypervascular enhancement in 39 of the 43 nodules
      (91%). Helical CT showed areas of high attenuation in 40 of the 43 nodules (93%),
      while DSA and US angiography showed positive enhancement in 38 and 43 of the 43
      nodules (88% and 100%), respectively. Digital subtraction imaging is useful for
      evaluating vascularity in HCC when the tumor can be visualized with non-enhanced
      US angiography.

PMID- 12066211
TI  - Flow cytometric analysis of DNA ploidy in primary, metastatic and recurrent
      breast cancers.
AB  - Although there have been many studies analyzing the heterogeneity of DNA ploidy
      either in primary breast cancer or between the primary and synchronous metastatic
      lesions of breast cancer, few studies have been made regarding a comparison of
      DNA ploidy between the primary and recurrent lesions of breast cancer. Flow
      cytometric analyses for DNA ploidy were performed on both the primary lesions and
      the matching synchronous metastatic lymph nodes of 104 breast cancers and on both
      the primary and matching recurrent lesions of 31 breast cancers. A concordance of
      DNA ploidy between the primary lesions and the matching metastatic lymph nodes
      was found in 80 (77%) cases, while a concordance of DNA ploidy between the
      primary and matching recurrent lesions was found in 22 (71%) cases. Forty-six
      (94%) of 49 cases showed less than an 8.0% difference in the DNA indices of the
      aneuploid peaks between the primary lesions and the metastatic lymph nodes, while
      13 (87%) of 15 cases showed less than 15.0% difference in the DNA indices between
      the primary and recurrent lesions. The aneuploid group and the heterogeneity
      group, divided according to the comparison of DNA ploidy between the primary and
      synchronous metastatic lesions, had a worse disease-free survival than that of
      the diploid group (p=0.0426 and p=0.0503, respectively). In conclusion, the
      majority of DNA ploidies are consistent among the primary, synchronous metastatic
      and recurrent lesions of breast cancer. The existence of aneuploidy itself may
      also play a prognostic role in breast cancer.

PMID- 12066213
TI  - Growth inhibitory effect of paradicsompaprika in cancer cell lines.
AB  - We investigated whether components of paradicsompaprika have direct antitumor
      effects or inhibitory effects on cancer growth, using its water extract. We
      applied collagen gel droplet embedded culture drug sensitivity test (CD-DST) as a
      screening method, which was developed based on the characteristics of cell
      culture on collagen matrix. Colon adenocarcinoma cells, epithelial cells of lung
      cancer, and cervical cancer cells were used. Paradicsompaprika is classified as
      Capsiucum annume L. var. grossum of Solanaceae. It is the first of the Hungarian
      species that was planted in Japan. It is available as TOMA-P in Japan. TOMA-P
      contains abundant carotenoids including capsanthin and beta-carotene. Water
      extract of paradicsompaprika was added to each cell at each concentration, and
      the mixture was cultured for 24 h and 7 days. The inhibitory effects against lung
      cancer and cervical cancer were observed concentration- and time-dependently. The
      effect was more prominent against lung cancer. The growth of bowel cancer cells
      was observed after the 7-day exposure of paradicsompaprika at the concentrations
      below the highest concentration compared to the control. At the highest
      concentration, the growth inhibition was not different between the 24-h exposure
      and the 7-day exposure, which suggests that tumor dormancy was induced. Results
      of the present study suggest that the water extract of paradicsompaprika can be a
      candidate of a new anticancer agent. Fat soluble component of paradicsompaprika,
      capsanthin is regarded as an anti-promoter of cancer. Thus, paradicsompaprika
      possesses chemopreventive and inhibitory effects on cancer cells.

PMID- 12066212
TI  - Postoperative adjuvant chemotherapy is effective in gastric cancer with serosal
      invasion: significance in patients chosen for multivariate analysis.
AB  - There are few reports on overall usefulness of adjuvant chemotherapy in gastric
      cancer patients. We tried to clarify, using multivariate analysis, usefulness of
      postoperative adjuvant oral chemotherapy in advanced gastric cancer patients
      after curative resection. Four hundred and eighty-two gastric cancer patients
      enrolled in a randomized controlled trial were classified into 2 groups based on
      postoperative chemotherapeutic regimen: oral doxifluridine (5'-DFUR, an
      intermediate metabolite of capecitabine) (n=245) or oral 5-fluorouracil (5-FU)
      (n=237). The significant prognostic factors in patients with serosal invasion
      were chemotherapeutics (5'-DFUR vs. 5-FU) (risk ratio 1.649; 95% CI, 1.112
      2.437), lymph node metastasis (no vs. yes) (2.823; 1.422-5.604), and tumor
      differentiation (differentiated vs. undifferentiated) (1.727; 1.068-2.791).
      Significant factors influencing peritoneal recurrence time were chemotherapeutics
      (1.756; 1.063-2.902), serosal invasion (no vs. yes) (2.237; 1.264-3.961), lymph
      node metastasis (2.541; 1.267-5.095), tumor differentiation (2.656; 1.374-5.136),
      and tumor location (others vs. total) (3.595; 2.006-6.443). There were no
      differences in the overall survival between chemotherapy. However, 5'-DFUR
      produced a better survival time of patients with serosal invasion than 5-FU, that
      might be attributed to the prevention of peritoneal recurrence in this subset.

PMID- 12066214
TI  - Oral fluoropyrimidine anticancer drug TS-1 for gastric cancer patients with
      peritoneal dissemination.
AB  - The survival of gastric cancer patients with peritoneal dissemination is dismal
      and surgical intervention is rarely indicated. The usefulness of TS-1, a novel
      oral anticancer drug, composed of tegafur, gimestat and otastat potassium at a
      molar ratio of 1:0.4:1, and the role of surgical intervention for this condition
      was studied. Among gastric cancer patients with peritoneal dissemination, 18
      treated during September 1999 to March 2001, and 16 before March 1999, were
      classified into the TS-1 group and control group, respectively, and survival was
      compared. TS-1 was administered orally twice daily, at a dose of 80 mg/m2/day,
      for 28 days followed by 14 days without treatment. This cycle was repeated. There
      was no difference in clinicopathologic factors, including surgical intervention,
      between the two groups. Eleven patients of the control group had chemotherapy
      using fluoropyrimidine. Grade 3-4 adverse reactions caused by TS-1 occurred in 1
      patient. Survival was better in the TS-1 group than control group (p=0.0008),
      with median survival of 257 vs. 118 days. The median discharged period of
      patients of the TS-1 group with a performance status 0-2 on the Zubor scale was
      211 days. TS-1 was effective to prolong the survival of gastric cancer patients
      with peritoneal dissemination. In this series of cases, surgical intervention to
      establish the route of oral administration was essential for this treatment.

PMID- 12066215
TI  - Preventive effect of fermented brown rice and rice bran against colon
      carcinogenesis in male F344 rats.
AB  - Epidemiological and preclinical studies demonstrate that nutrition plays an
      important role in the etiology of cancer. It has been reported that rice
      components, especially rice germ plays a key role in prevention of cancer. The
      experiments described here examined the potential anticancer properties of brown
      rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of
      the formation of azoxymethene (AOM) induced aberrant crypt foci (ACF) and tumors
      in the colon as the measure of preventive efficacy. The agent was administered at
      2.5 and 5% levels in the diet during the initiation phase (during and until 1
      week after carcinogen treatment) and/or post-initiation phase (beginning 1 week
      after carcinogen treatment) of carcinogenesis. In the ACF and tumor studies, rats
      were sacrificed 5 or 40 weeks after the initiation of AOM treatment (15 mg/kg
      body weight, once weekly for 3 weeks), respectively. Colonic ACF and tumors were
      evaluated histopathologically. Administration of 2.5 and 5% FBRA in the diet
      continuously during initiation and post-initiation period significantly inhibited
      the ACF formation in rats treated with AOM, compared with rats treated with AOM
      alone (99+/-24.1 and 79+/-18.4 vs. 139.5+/-27.7, respectively). In addition,
      administration of 5% FBRA in the diet during the post-initiation phase
      significantly suppressed the incidence (44 vs.18%) and multiplicity (0.93+/-0.96
      vs. 0.18+/-0.40) of colon adenocarcinomas as compared to those given the control
      diet. In addition, 5% FBRA in the diet during post-initiation phase caused
      significant inhibition of cell proliferation in the colonic mucosa as compared to
      the group fed the control diet (81% reduction, p<0.05). These observations
      demonstrated for the first time that FBRA inhibits colon tumor development in
      rats, and suggest that it is a promising dietary supplement for prevention of
      human colon cancer.

PMID- 12066216
TI  - Fas expression inversely correlates with metastatic potential in osteosarcoma
      cells.
AB  - A complex series of steps must take place to allow for a single cell to
      metastasize. Identifying factors responsible for these steps is essential in
      developing targeted therapy. We developed series of osteosarcoma cell lines with
      differing metastatic potentials. We used them to investigate mechanisms of
      metastasis and possible therapeutic targets for osteosarcoma metastasis to the
      lung in a nude mouse model. No correlation was found between epidermal growth
      factor receptor (EGFR), insulin-like growth factor receptor inhibitor (IGF-I-R),
      gelatinase, p53, metalloproteinase 9 (MMP 9), platelet derived growth factor
      receptor (PDGF-R), vascular endothelial growth factor (VEGF) and c-met expression
      and metastatic potential as measured by Northern analysis. By contrast, Fas
      expression inversely correlated with metastatic potential, and manipulation of
      Fas expression altered the metastatic phenotype of the cell. Our data indicate
      that fas gene expression may offer a new therapeutic target for the treatment of
      metastatic osteosarcoma in the lung.

PMID- 12066217
TI  - Genetic discordance between primary tumours and metastases of head and neck
      cancer detected by microsatellite analysis.
AB  - Very little is known about possible intra-tumoural genetic heterogeneity between
      primary tumours and lymph node metastases in head and neck squamous cell
      carcinoma (HNSCC). To investigate this phenomenon, we analysed 96 micro-dissected
      tumour samples for allelic imbalance at four of the most frequently altered
      chromosomal locations in HNSCC (3p14.2; 9p21; 11q23.3; 17p13.1) using
      microsatellite markers. From 23 patients, matched pairs of primary tumour and
      lymph node metastasis were analysed. Discordance in the allelic distribution was
      identified in 8 cases (35%). With one exception, the metastasis contained a more
      balanced allelic status than the primary tumour. In contrast, in a group of 25
      tumours with two anatomically different samples from the primary tumour site,
      discordance was identified in only 3 tumours (13%). These results are compatible
      with the dissemination of subclones from the primary tumour site with a more
      balanced allelotype in the metastasis. In our opinion, several scenarios could
      explain this phenomenon. From a clinical point of view, genetic discordance
      between the metastasis and the primary tumour must be taken into consideration
      when establishing molecular biologic markers for choice of therapy and prognosis
      in head and neck cancer.

PMID- 12066218
TI  - Expression of survivin correlated with vessel invasion is a marker of poor
      prognosis in small adenocarcinoma of the lung.
AB  - The purpose of this study was to investigate the possible association between
      expression of survivin, pathological findings in the tumor and survival in
      patients with small adenocarcinoma of the lung. Seventy-nine patients with
      resected tumors <2 cm in diameter were entered into the study. There were 33
      males and 46 females, with a median age of 64 years (range 26-83 years). The
      pathological stage of the tumors was recorded as stage I, II, III and IV in 72,
      one, five and one case, respectively. Each patient underwent curative surgical
      resection for lung cancer between July 1992 and November 1999. The resected
      tumors were subjected to immunostaining for survivin. Thirty-eight patients had
      tumors with < or = 10% survivin-positive cells and 41 patients had tumors with
      >10% survivin-positive cells. When survivin expression and pathological findings
      in the resected tumors were analyzed, the frequency of venous invasion was
      significantly higher in the survivin-positive group (36.6% vs. 13.2%; p=0.0167).
      In contrast, the overall survival of survivin-positive patients (n=41) was
      significantly worse than that of individuals whose tumors were negative for
      survivin expression (n=38; log-rank test, p=0.014; Wilcoxon test, p=0.021). It
      can be concluded that the expression of survivin in tumor cells is a factor of
      poor prognosis in patients with small adenocarcinoma of the lung.

PMID- 12066219
TI  - Enhanced nucleotide excision repair in cisplatin resistant human KB carcinoma
      cells.
AB  - We previously reported that enhanced active efflux of cisplatin and increased GSH
      level were observed in KCP-4 cells. In the present study, KCP-4 cells were found
      to be cross-resistant to ultraviolet (UV) compared with parental KB-3-1 cells.
      Enhanced nucleotide excision repair (NER) was verified by time-dependent repair
      of UV-induced DNA damage. In addition, the amount of platinum bound to DNA after
      exposure to cisplatin decreased in a time-dependent manner in KCP-4 cells and
      this was reversed by aphidicolin, a DNA polymerase inhibitor. In stationary phase
      cultures, aphidicolin increased the sensitivity of KCP-4 cells to cisplatin. The
      expression of xeroderma pigmentosum complementation group F (XPF), an
      endonuclease involved in NER, was upregulated in KCP-4 cells. In KCP-4 cells the
      expression of hMSH6, one of the mismatch repair (MMR) factors, was decreased
      compared to parental KB-3-1 and revertant KCP-4R cells. However, KCP-4 cells were
      cross-resistant to oxaliplatin, and microsatellite instability was not observed
      in them. These findings suggest that the enhanced NER activity for DNA damage
      caused by cisplatin may be involved in cisplatin resistance in KCP-4 cells.

PMID- 12066220
TI  - Immunohistochemical heterogeneity of type 1 blood group antigen expressions in
      testicular germ cell tumors.
AB  - The immunohistochemical expression of type 1 blood group antigens (type 1 BGAs)
      was analyzed for 30 cases of testicular germ cell tumors (TGCTs), using
      monoclonal antibodies against DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b)
      (Le(b)). DU-PAN-2 was expressed very frequently in all of the embryonal
      carcinomas (ECs). CA19-9 expression was demonstrated in 53% of ECs, but the
      number of positive cells was generally smaller than that for DU-PAN-2. CA19-9
      negative ECs tended to show a higher number of DU-PAN-2-positive cells compared
      to CA19-9-positive ECs, and ECs in which DU-PAN-2 was more strongly expressed
      showed a relatively frequent expression of CA19-9. In 36% of seminomas and 56% of
      yolk sac tumors (YSTs), DU-PAN-2 was weakly expressed, and the positive cells
      were few in number. Little or no expression of CA19-9 was demonstrated in
      seminomas and YSTs. Regarding Le(a) and Le(b), the expressions were found to be
      limited to teratomas at a frequency of 57% and 86%, respectively, with the
      exception of one EC positive for Lea and one YST positive for Leb. Eighty-six
      percent of teratomas showed expressions of DU-PAN-2 and CA19-9. DU-PAN-2 was also
      seen in some intratubular malignant germ cells. The antibodies used were all
      negative for choriocarcinomas, syncytiotrophoblastic giant cells, and normal
      testicular tissues. The antigen expressions were predominantly observed on the
      surface of tumor cells developing luminal structures. In conclusion, although
      CA19-9 was relatively specific for ECs, it should be emphasized that ECs were
      rather characteristic of extensive DU-PAN-2 expression. Particularly in CA19-9
      negative ECs, a combined analysis of DU-PAN-2 and CA19-9 would be helpful in
      confirming the histopathologic diagnosis of TGCTs. The clinical significance of
      DU-PAN-2 in ECs as a tumor marker remains to be clarified. Le(a) and Le(b)
      expressions were thought to be related to the differentiation or maturation
      rather than to the malignant transformation in TGCTs.

PMID- 12066221
TI  - Ets-2 overexpression contributes to progression of pancreatic adenocarcinoma.
AB  - Ets-2, a transcriptional factor, has been linked to carcinoma progression but in
      depth studies on its expression in human carcinoma have not been done. The
      present study investigated ets-2 expression in pancreatic adenocarcinoma. The ets
      2 labeling index (LI) in normal pancreatic duct and pancreatic adenocarcinoma
      averaged 33.1+/-8.4 and 43.1+/-18.6, respectively. No statistical significance
      was found between the LI of normal duct and that of carcinoma with low biological
      aggressiveness. However, in cases with highly aggressive phenotypes such as stage
      IV, moderate or poor differentiation, lymph node metastasis, larger size,
      vascular invasion, lymphatic invasion, perineural invasion, retropancreatic
      invasion and capsular invasion, the ets-2 LI was significantly higher than in
      normal ducts and in cases with lower biological aggressiveness. Also, ets-2
      transfected pancreatic carcinoma cells, when injected into athymic mice caused
      the formation of large tumors. These results suggest that ets-2 plays a role in
      the progression of pancreatic adenocarcinoma predominantly in the late phase.

PMID- 12066222
TI  - Low dose of wortmannin reduces radiosensitivity of human glioblastoma cells
      through the p53 pathway.
AB  - Wortmannin is an inhibitor of PI3-kinase and acts on cultured cells at dosages
      below 1 microM. Wortmannin also inhibits the gene products of the PI3-kinase
      family such as ATM or DNA-PK at dosages above 10 microM in cultured cells. There
      are many reports on the enhancement of radiosensitivity by a high dose of
      wortmannin inhibiting the proteins of the PI3-kinase family. However, there have
      been no reports on the effect on radiosensitivity of low doses of wortmannin
      inhibiting PI3-kinase. We found that low doses of wortmannin reduced the
      radiosensitivity of human A172 glioblastoma cells. This effect was shown only in
      wild-type p53 cells, but was not shown in mutant p53 cells such as T98G or
      A172/248W carrying a dominant point-mutated p53 gene. This result indicates that
      the PI3-kinase, or another wortmannin-sensitive enzyme, may affect the signal
      transduction of p53. We examined the response of the p53 pathway by X-ray
      irradiation. A low dose of wortmannin did not affect the accumulation of p53 and
      the phosphorylation of p53 at ser-15, but reduced the induction of WAF1 and
      enhanced the induction of GADD45.

PMID- 12066223
TI  - Sarcoma and thyroid disorders: a common etiology?
AB  - We have recently observed that many of our sarcoma patients presented also with
      thyroid disorders. Literature data are almost unavailable on this topic. The
      relationship between the sarcoma and thyroid disorders is examined. Retrospective
      analysis of files of patients with sarcoma and clinically overt thyroid disorders
      was carried out. Of the 375 patients with soft tissue sarcomas (STS) and 235 with
      bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients
      (4.6%) had an associated significant thyroid disorder. The types of sarcoma were
      mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and
      bone sarcoma. The primary sites were mainly limb and trunk. The interval between
      the diagnosis of the thyroid disorder and the sarcoma varied between -14 years
      (thyroid first) and +16.5 years (thyroid later) with a median of -0.2 years.
      Thyroid disorders included goiter, thyroiditis and carcinoma. There are both
      basic-science and clinical evidence to a possible common pathway that leads to
      the association between overt thyroid disorders and sarcomas of bone or soft
      tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to
      development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might
      contribute to the development of sarcoma. The thyroid hormone receptor and the
      highly related viral oncoprotein v-erbA are found exclusively in the nucleus as
      stable constituents of chromatin. It has been shown that v-erbA can block the
      spontaneous differentiation in erythroid cells transformed by various retroviral
      oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src
      oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The
      erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and
      c-kit. Cooperation with v-myc may play a role in the development of
      rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible
      clinical implications are the need to screen patients with sarcoma to thyroid
      disorders, and patients with thyroid disorders for malignant diseases.

PMID- 12066224
TI  - HPV detection in cervical cancer patients in northern Poland.
AB  - Human papillomaviruses (HPVs) are associated with various benign and malignant
      lesions including genital condyloma and anogenital cancer. Epidemiological data
      show that about 90% of all cervical cancer patients are HPV positive. The aim of
      our study was to determine the percentage of HPV infections in Polish population
      of examined women. To detect viral DNA, PCR method was used. To distinguish
      between different virus types, RFLP analysis was performed. Results obtained by
      PCR-RFLP method were verified by Hybrid Capture test. The presence of HPV DNA was
      detected in 53% of cervical cancer patients and in 2% of control group of healthy
      women. The agreement for HPV detection between PCR and Hybrid Capture methods was
      81%. Our studies showed much lower incidence of HPV in Polish women with cervical
      cancer than among other populations as reported in world literature. HPV
      detection as well as determination of other factors involved in pathogenesis of
      cervical cancer is of great importance.

PMID- 12066225
TI  - Basic fibroblast growth factor mediated growth inhibition in breast cancer cells
      is independent of ras signaling pathway.
AB  - Our previous studies have demonstrated that basic fibroblast growth factor (bFGF)
      inhibits the growth of MCF-7 human breast cancer cells via binding to high
      affinity cell surface receptors. The downstream signaling of bFGF was reported to
      involve the ras pathway. The aim of the present study was to examine the bFGF
      induced growth inhibition in the presence of lovastatin, a farnesyl transferase
      inhibitor, which impaired ras signaling by preventing its association with the
      plasma membrane. We found that the combined cytotoxicity induced by lovastatin
      and bFGF was greater than the cytotoxicity induced by each agent alone.
      Similarly, the protein level of P21/WAF1/cip1 was greater after exposure to both
      agents together, than separately. bFGF did not interfere with the lovastatin
      induced inhibition of P21/RAS membrane association, while lovastatin did not
      prevent MAPK activation by bFGF. Based on these findings we suggest that the
      growth inhibitory effect of bFGF on breast cancer cells is largely independent of
      the ras signaling pathway. Understanding these pathways may enable active
      intervention to alter the therapeutic ratio favorably in the treatment of breast
      cancer.

PMID- 12066226
TI  - Synergistic interaction between highly specific cyclooxygenase-2 inhibitor, MF
      tricyclic and lovastatin in murine colorectal cancer cell lines.
AB  - Statins, anti-hypercholesterolemic agents, have previously been reported to
      induce apoptosis and exert antitumor activity when combined with other antitumor
      agents. The potential of lovastatin in combination with highly specific COX-2
      inhibitor (MF-tricyclic) to induce anti-proliferative activity against tumour
      cells was evaluated using the combination index (CI) method. Murine colorectal
      cancer (colon-26, CMT-93), melanoma (B16F10) and human bladder carcinoma cells
      (T24) were tested. Exposure of colon-26 and CMT-93 cells resulted in synergistic
      interactions in both cell lines with CI<1 for 20-80% inhibition of cell growth in
      both cell lines. This synergy was not observed in the B16F10 melanoma and T24
      bladder carcinoma cells. MF-tricyclic (40 microg/ml), augmented lovastatin
      induced apoptosis up to 2.5-fold in colon-26 cancer cells. Combination of a
      specific COX-2 inhibitor, MF-tricyclic, may increase antiproliferative effects of
      lovastatin in colon cancer cells and this effect was due to an augmented
      apoptosis.

PMID- 12066227
TI  - Phase II study of subcutaneously administered interleukin-2 in combination with
      medroxyprogesterone acetate and antioxidant agents as maintenance treatment in
      advanced cancer responders to previous chemotherapy.
AB  - An open, non-randomized phase II study was carried out including patients with
      advanced solid tumors who achieved an objective response or disease stabilization
      as a result of previous chemotherapy, to receive a maintenance treatment with
      recombinant interleukin-2 (rIL-2) plus medroxyprogesterone acetate (MPA) plus
      antioxidant agents alpha-lipoic acid (ALA) and N-acetyl cysteine (NAC). The first
      study endpoints were to define clinical outcome and toxicity as well as the
      evaluation of quality of life. As secondary endpoints we measured the changes of
      lymphocyte absolute count, the serum levels of proinflammatory cytokines, IL-2, C
      reactive protein (CRP) and leptin after treatment. rIL-2 was administered at a
      dose of 1.8 MIU subcutaneously 3 times/week on alternate days for the first two
      weeks of every month and MPA was given orally at a dose of 500 mg/day at
      alternate days without interruption. ALA 300 mg/day orally and NAC 1800 mg/day
      orally were also administered continuously. Twenty-eight patients were enrolled
      in the study. The median duration of maintenance treatment was 10 months (6-30+).
      The response to maintenance treatment at September 15, 2001 was: CR 11 patients
      (39.3%); SD 2 patients (7.1%); PD 15 patients (53.6%). The median duration of
      response was 11 months (6-34+). The median follow-up duration was 11 months (6
      34+). The median OS was not reached. The median PFS was 21.5 months (1-40+). The
      1-year survival rate was 72.2%. At September 15, 2001, 16 patients were still
      surviving. No grade 3/4 toxicity and one grade 2 skin toxicity were observed. We
      found a significant increase of the absolute lymphocyte count and serum levels of
      IL-2 and a significant decrease of TNF alpha after treatment. The evaluation of
      patient subgroups showed the following: the patients alive at the end of study
      had a significant increase of lymphocyte count, IL-2 and leptin, and a
      significant decrease of IL-1 beta, IL-6 and TNF alpha, whereas the patients who
      had died had only a significant increase of lymphocyte count and IL-2. Among the
      patients alive, those in objective clinical response (CR + PR) + those in SD had
      a significant increase of lymphocyte count, IL-2 and leptin and a significant
      decrease of IL-1 beta, IL-6 and TNFalpha, whereas those with PD had no
      significant changes in any of the above values. We conclude that the combination
      of s.c. rIL-2 with oral MPA and anti-oxidant agents ALA and NAC in an
      intermittent schedule, repeated for a long-term period, is feasible, has a very
      low toxicity and results in the improvement of biological markers which are
      predictive for patient outcome.

PMID- 12066228
TI  - Inconclusive presence of adenovirus sequences in human leukemias and lymphomas.
AB  - Adenoviruses are ubiquitous viruses related to human mild upper tract respiratory
      infections. Murine cells are semi-permissive to adenovirus replication, and
      persistent or abortive infections have been associated with tumorigenic
      potential. Given that only human lymphoid cells are semi-permissive and abortive
      infections have been described, we hypothesized that adenovirus could be related
      to the transformation of human haematopoietic cells. We studied 30 lymphomas, 46
      leukemias, 10 reactive lymphadenopathies and 40 normal human spleens. The
      presence of adenovirus sequences and proteins were studied using PCR, southern
      blot, slot-blot, in situ hybridization, immunohistochemistry, and western-blot
      techniques. By using nested PCR, adenovirus sequences were detectable in about
      30% of lymphomas, but in less than 10% of leukemias, reactive lymphadenopathies
      and normal spleens. In no case were we able to demonstrate adenovirus products by
      in situ hybridization, immunohistochemistry or western-blot. These results
      indicate that adenovirus sequences are present in a significant number of human
      lymphomas, but that the number of positive cells is extremely low and no protein
      expression could be detected. Therefore, we are unable to conclude that
      persistent infections of human lymphoid cells by adenovirus is related to a
      higher risk of developing malignant lymphomas or leukemias.

PMID- 12066229
TI  - Treatment of hepatocellular carcinoma with long acting somatostatin analogues.
AB  - An earlier report has shown that subcutaneous short acting octreotide
      significantly improves survival of patients with inoperable hepatocellular
      carcinoma (HCC). The aim of this study was to compare survival of the patients
      with inoperable HCC treated with long acting somatostatin analogues (LASA) to a
      historical control group of untreated patients. The survival of 32 patients with
      inoperable HCC who received LASA treatment was compared to those of 27 untreated
      patients. The Karnofsky scale was used for assessing quality of life. An improved
      overall survival was found in the treated group (median survival 15 months, 95%
      CI 6-24 months for the treated group and 8 months, 95% CI 5-11 months for the
      controls). The survival benefit remains even after removal of the most advanced
      cases from the control group. The relative risk of death of the untreated
      patients is 2.7 (95% CI 1.4-5.3) compared to the treated patients. The tumor
      remained stable or regressed in 40% of the treated patients. A superior quality
      of life was found in the treated group. In conclusion long acting somatostatin
      analogues appear to be beneficial, improving survival and performance status in
      inoperable HCC cases. Further studies are required to define a subgroup of
      patients that may benefit to a greater extent than others.

PMID- 12066232
TI  - Current status of gastrointestinal MRI.

PMID- 12066233
TI  - MRI of esophageal cancer.

PMID- 12066234
TI  - Oral contrast agents in MRI of the gastrointestinal tract.

PMID- 12066235
TI  - MRI in staging of gastric cancer.

PMID- 12066236
TI  - MRI evaluation of Crohn's disease of the small and large bowel with the use of
      negative superparamagnetic oral contrast agents.

PMID- 12066238
TI  - MR colonography: status and perspective.
AB  - With further improvements in multislice CT, enabling now the combination of lung
      and colon imaging within one breathhold with automated dose optimization, MR
      colonography has almost been given up. But similar to angiography, we are
      optimistic that MR can be compatible to CT in colonography and report in this
      article on the current status and perspective of MR colonography. For more
      information see www.multiorganscreening.org.

PMID- 12066237
TI  - MRI of the abdomen with positive oral contrast agents for the diagnosis of
      inflammatory small bowel disease.
AB  - Magnetic resonance imaging (MRI) is being used more often in the evaluation of
      inflammatory bowel diseases. A prerequisite for adequate image quality is the
      oral application of contrast medium, which can be administered with different
      modalities. Positive and negative oral contrast media can be used; in terms of
      diagnostic efficacy, there appears to be no relevant differences between them.
      Sequences usually are acquired using breath-hold or respiration-triggered
      protocols. The underlying principle is visualization of circumscribed thickening
      of the intestinal wall, which shows a pathologic pattern of contrast medium
      uptake. The available data suggest that MRI is equally as effective as
      enteroclysis in the primary diagnosis of Crohn's disease and actually more
      sensitive in the detection of extraintestinal manifestations such as fistulae or
      abscesses. Supporters of the method predict that MRI will replace enteroclysis in
      the long term.

PMID- 12066239
TI  - Fecal tagging: MR colonography without colonic cleansing.
AB  - Colorectal cancer, mostly arising (>90%) from preexisting adenomatous polyps,
      continues to be the second leading cause of cancer death. Magnetic resonance
      colonography (MRC) permits accurate detection of colonic polyps with a diameter
      larger than 10 mm. Because residual colonic stool cannot be differentiated from
      polyps, MRC requires a clean colon. However, the rigors associated with colonic
      cleansing considerably reduce patient acceptance. The need for colonic cleansing
      could be eliminated, if stool were to acquire a signal intensity different from
      polyps and identical to the enema used to fill and distend the colon. In
      principle, there are two approaches to this concept of fecal tagging: dark polyps
      surrounded by bright stool and a bright enema, and bright polyps surrounded by
      dark stool and a dark enema. The first approach has been evaluated with some
      success. Gadolinium (Gd)-DOTA was administered as an oral contrast agent with
      meals preceding MRC based on the administration of a Gd-based enema. The high
      cost of Gd-based contrast has limited the clinical utility of this technique. In
      the second approach patients are provided with barium as an oral fecal tagging
      agent to render stool dark, and barium for the enema is used to distend the colon
      during MRC. The colonic wall and polyps arising from it can be made visible after
      intravenous administration of Gd-based extracellular contrast. This method
      provides sufficient contrast between the darkened colonic lumen and the brightly
      enhanced colonic wall to permit virtual endoscopic rendering. Preliminary results
      showed an exact correlation with findings of conventional endoscopy and surgery.
      Fecal tagging obviates bowel cleansing and therefore should enhance patient
      acceptance for MR colonoscopy. Barium as the tagging agent is promising because
      it is inexpensive, commercially available, and characterized by an excellent
      safety profile.

PMID- 12066240
TI  - MRI of colorectal cancer.

PMID- 12066241
TI  - Local staging of rectal cancer with MRI using a phased array body coil.

PMID- 12066242
TI  - Current and future perspectives on the role of internal coils for magnetic
      resonance imaging of the anal sphincter and rectum.

PMID- 12066243
TI  - Scintigraphic pattern of planar gallium scan in wound infection after colorectal
      surgery.
AB  - BACKGROUND: The incidence of postoperative wound infection is higher after
      colorectal surgery than after other surgical procedures. No studies have
      evaluated the usefulness of gallium 67 scintigraphy for detecting wound infection
      after colorectal surgery. We investigated the clinical potential of gallium
      imaging for detecting wound infection after colorectal surgery. METHODS: Fifty
      patients who had fever after colorectal surgery were enrolled in this study. All
      patients had open surgical incisions at the midline of the abdomen. Planar
      gallium scintigraphy was performed 24 h, and then as needed, after the injection
      of 111 MBq (3 mCi) Ga 67 citrate. All scans were interpreted by two physicians
      specializing in nuclear medicine. Intensities of gallium uptake at the surgical
      wound were recorded as grades 0 (no uptake), 1 (less than liver uptake), 2 (equal
      to liver uptake), or 3 (greater than liver uptake). When the intensity of gallium
      uptake was equal to or greater than grade 2, gallium uptake was classified as two
      patterns: regular and irregular. RESULTS: Eighteen patients were diagnosed with
      wound infection. When interpretation was based on only gallium-uptake intensity,
      the diagnostic sensitivity, specificity, and accuracy of the gallium scan were
      100%, 75%, and 84%, respectively. When interpretation was based on gallium-uptake
      intensity and pattern, the diagnostic sensitivity and specificity were 94.4% and
      96.9%, respectively. The diagnostic accuracy had increased, from 84% to 96%.
      CONCLUSION: Planar gallium scan is useful for detecting wound infection after
      colorectal surgery. Gallium-uptake pattern and intensity are important for
      interpreting planar gallium scans.

PMID- 12066244
TI  - Does the addition of an oral barium tracer improve the ability of the preliminary
      abdominal radiograph to assess efficacy of colonic cleansing? A prospective
      randomized controlled evaluation.
AB  - BACKGROUND: We investigated whether the ability of preliminary abdominal
      radiography to assess the adequacy of colonic preparation is improved by the
      addition of an oral barium tracer to the laxative preparation and the optimal
      dosage of this tracer. METHODS: A single-blind, randomized controlled evaluation
      of four parallel groups of adult patients was performed. All patients were
      scheduled to a receive a double-contrast barium enema at a tertiary care hospital
      or an outpatient clinic. RESULTS: One hundred nineteen patients were randomized
      into four groups. There was no significant difference in the ability of plain
      abdominal radiography to predict the adequacy of the bowel preparation between
      the control group and the groups given 60 or 150 g of barium tracer. There was an
      improved correlation between findings of preliminary abdominal radiography and
      the adequacy of colon preparation between the control group and the group given
      240 g of oral barium tracer (67% vs. 90%). CONCLUSION: The use of a large amount
      (240 g) of oral barium tracer with the colonic preparation improves the ability
      of preliminary abdominal radiography to predict the adequacy of colonic
      cleansing.

PMID- 12066245
TI  - Perforations of the rectosigmoid colon induced by cleansing enema: CT findings in
      14 patients.
AB  - BACKGROUND: We report the computed tomographic (CT) features of colorectal
      perforations caused by cleansing enema. METHODS: We reviewed the medical records
      and CT studies of all patients with colorectal perforations caused by a cleansing
      enema. RESULTS: Fourteen patients (10 men, four women; average age = 80 years)
      were included in the study. The most common presenting symptoms were severe
      abdominal pain and fever. CT was performed within 48 h after the event in most
      patients. Extraluminal air in the perirectal fat was the most frequent finding on
      CT and was present in all patients. Additional findings were extraperitoneal ( n
      = 9), intraperitoneal ( n = 3) and /or subcutaneous ( n = 3) air, free fluid ( n
      = 9), extraluminal feces ( n = 8), and focal bowel wall thickening ( n = 4). No
      leak of contrast from the rectum was observed in any patient including the one
      patient in whom contrast was administered rectally. Ten patients were treated by
      surgery; five recovered and the other five died. The other four patients were
      treated conservatively and all four died. CONCLUSION: The diagnosis of colorectal
      perforation can be made on CT. Because the diagnosis is not always suspected by
      the clinician, the radiologist may be the first to suggest it. Therefore, the
      radiologist should be familiar with the CT features of a potentially lethal,
      rectally induced perforation.

PMID- 12066246
TI  - Nontraumatic hepatic artery pseudoaneurysm associated with acute leukemia: a
      possible complication of pyogenic liver abscess.
AB  - Most hepatic artery pseudoaneurysms result from trauma, blunt or penetrating,
      such as that caused by percutaneous transhepatic procedures. We present a case of
      hepatic artery pseudoaneurysm resulting from a pyogenic liver abscess, which has
      not been described previously, in a patient with acute leukemia receiving
      chemotherapy.

PMID- 12066247
TI  - Abdominal lymphoma: differentiation from pancreatic carcinoma with Doppler US.
AB  - BACKGROUND: Marked lymphadenopathy around the pancreas due to lymphoma (abdominal
      lymphoma) occasionally can mimic a total pancreatic carcinoma on ultrasonography
      (US). We investigated whether US and color Doppler US allowed differentiation
      between those pathologies. METHODS: We analyzed the US and color Doppler results
      of 12 cases of abdominal peripancreatic lymphoma and 21 cases of total pancreatic
      carcinoma. RESULTS: With regard to shape, echogenicity of the lesion, and mode of
      vascular involvement, there was no difference between groups. With regard to
      maximal velocities and resistive indices of the involved vessels, there was no
      difference between groups. However, the presence of turbulent flows in the
      involved vessels was seen exclusively in the pancreatic carcinoma group.
      CONCLUSION: The presence or absence of turbulent flow in the involved vessels is
      a very important finding for differentiating abdominal lymphomas from total
      pancreatic carcinomas.

PMID- 12066248
TI  - Abdominopelvic tuberculosis simulating disseminated ovarian carcinoma with
      elevated CA-125 level: report of two cases.
AB  - We report the radiologic presentations of two cases of peritoneal-pelvic
      tuberculosis. The initial interpretation based on the adnexal masses, ascites,
      omental and peritoneal thickening, and elevated serum CA-125 levels led to an
      erroneous preliminary diagnosis of disseminated ovarian cancer. In both patients,
      histologic examination showed tuberculosis. The clinical and radiologic findings
      resolved significantly after several months of multidrug antituberculosis
      treatment.

PMID- 12066252
TI  - [Acute care versus rehabilitative care].

PMID- 12066253
TI  - [Psyche - soma - delinquency. Empirical and clinical datas of psychosomatic
      disturbed delinquents: discussion and survey].
AB  - Psychosomatic disorders of delinquents are current clinical phenomena, but they
      are rarely examined and discussed. The contribution presents empirical
      statistical results of a field-study with n = 202 unselected forensic patients in
      disciplinary measures. Psychosomatic diseases have been diagnosed in n = 48
      cases. The interpretation of multi- and bivariate statistics hints at an
      iatrogene influence on detainees: Their psychosomatic disorders can be described
      as forms of autoplastic defence which must be considered in the context of
      specific basic personality structures and corresponding disturbed ego functions
      (control of impulses and anxiety, competence of communication and sublimation).
      This psychosomatic structure can be differentiated from perverse structured
      personalities. Characterised as an autoplastic and auto-aggressive reaction, the
      psychosomatic symptom can be distinguished from alloplastic and hetero-aggressive
      acting. Nevertheless these psychodynamics seem to be forensic-psychological
      predicators for anticipated delinquent relapses.

PMID- 12066254
TI  - [Psychophysiological and psychological aspects of mild hypertension].
AB  - The aetiopathogenesis of essential hypertension has been more intensively
      investigated in recent years mainly in genetic high-risk groups and patients with
      transitory and early forms of essential hypertension. A group of 29 patients with
      mild hypertension according to the WHO criteria were submitted to
      hypertensiological, psychological and psychophysiological specification in this
      study. Twenty-four hour blood measurements were performed for this purpose. The
      group could thus be divided into 18 patients with white-coat hypertension (WH)
      and 11 patients with real mild hypertension (H). Contrary to expectations, mild
      hypertensives had weaker systolic (p < 0.05) and diastolic (p < 0.01) blood
      pressure reactions to mental stress than white-coat hypertensives. Their
      cardiovascular recovery was not reduced after stress. Psychological differences
      between the groups were only found with respect to irritability (FP1: H 6.9 sd
      2.1, WH 5.2 sd 2.1 stanine) and hypertensives compared to the reference random
      sample on the FPI scale emotional instability (6.5 stanine). Other psychosomatic
      studies should replicate the results obtained in this study in larger patient
      populations with white-coat and mild hypertension.

PMID- 12066255
TI  - [Group cohesion and defensive behavior in the course of inpatient group
      therapies].
AB  - This paper examines the connection between the therapy success, group cohesion
      and defence-formation during an inpatient psychoanalytically oriented group
      therapy treatment. Over a period of one year, the Stuttgarter Bogen was given
      every third week after each therapy group. At the beginning and at the end of the
      three-month treatment, the patients were examined with the defence-mechanism
      computer test (Abwehrmechanismus-Computer-Test, ACT) and SCL-90-R. In addition,
      the 48 patients were divided into a successful and unsuccessful group by means of
      the General-Symptom-Index (GSI) of the SCL-90-R. On the whole, the results
      stressed the importance of group cohesion as a factor with a major influence on
      therapeutic efficacy. In the defences, there is a dominance of projective and
      introjective mechanisms. In the group of successful patients, there was an
      increase in group cohesion as well as a change in individual defence-mechanisms
      over the course of treatment: Repression increased and identification with the
      aggressor decreased. In the case of the unsuccessful patients, on the other hand,
      there was increased regression in the defences over the course of treatment, and
      there was no change in group cohesion. Accordingly, the connections found between
      group cohesion and defencemechanisms can be regarded as an indication of internal
      stabilization in the successful patients, whereas the findings for the patients
      that did not improve represent a reaction to excessive strain.

PMID- 12066256
TI  - [Dogs, man-wolves and full moon].
AB  - According to a study of the British Medical Journal in England the incidence of
      dog bites increases at the time of a full moon. The following article first
      passes the myths dealing with the werewolf. By changing from delinquent to
      patient during the Enlightenment the werewolf gets important to the history of
      medicine and psychiatry. From the anthropological point of view the so-called
      Lycorexia may be understood as an unconscious effort to undo evolution by
      transformation into beast. By the figure of the "Huckup" in recent variants
      concerning the werewolf subject a psychological turn of the legend is expressed.

PMID- 12066257
TI  - [The connection between affective evaluation of recollected relationship
      experiences and the severity of the psychic impairment].
AB  - This study, carried out at three different university centers contributes to
      validating the valence dimension of the CCRT-method. Working on the state of the
      CCRT-research on affective evaluation of relationship narratives, the connection
      between the valence dimension of the responses from others (RO), responses of the
      self (RS) and the severity of the psychic disorder has been analysed with the
      help of two different samples (n = 266 resp. n = 32) taken from female patients.
      Both, therapists as well as patients themselves, evaluated the severity of the
      impairment similarly. The more the patients were impaired, the more negatively
      they describes both their own reactions and those of their interaction partners
      as shown in the relationship episodes.

PMID- 12066258
TI  - Editorial: The chance of a lifetime.

PMID- 12066259
TI  - International hematology-oncology nursing education in Latin America.
AB  - In countries with limited resources, the multidisciplinary hematology-oncology (H
      O) treatment team model, which relies heavily on highly trained nurses, is
      generally not in use. Since 1996, St. Jude Children's Research Hospital has been
      working with medical centers in Mexico and Central and South America to improve
      the specialty training of nurses in pediatric H-O. In 1999, St. Jude developed a
      strategic plan to organize a cooperative nursing education project. The initial
      preparation consisted of three phases. In phase one, a curriculum was developed.
      A consultant was hired to create and institute an evaluation system for nurse
      graduates of the program and for the program itself. Phase two explored the
      possible collaborations among existing training centers and contracted with a
      nurse educator to provide on-site support. In phase three, a core team of skilled
      multicultural nursing educators was formed. To initiate the program, we used the
      "Teach the Teachers" method. Four classes to date have trained 76 nurses from
      different countries in Latin America. Development of the International Training
      Center for Hematology-Oncology Nurses in Latin America has been a challenging and
      rewarding experience. We hope that others will find it useful in planning
      international education programs that will not only serve the nursing profession,
      but also improve the quality of care of all children, regardless of their
      background, race, religion, or economic status.

PMID- 12066260
TI  - The role of the primary care advanced practice nurse in evaluating and monitoring
      childhood cancer survivors for a second malignant neoplasm.
AB  - The purpose of this literature synthesis was to (a) identify second malignant
      neoplasms found in childhood cancer survivors and (b) make recommendations for
      the advanced practice nurse's role in the primary care setting regarding health
      promotion activities and surveillance strategies for survivors across the life
      span. The database search produced 73 research articles published in English
      between 1990 and 2000 that were significant to the purpose of the study. The
      results identified genetic or familial factors, radiation therapy, and
      chemotherapy as risk factors for later developing a second malignant neoplasm.
      Each theme was analyzed, and guidelines were developed for primary care advanced
      practice nurses which integrated health promotion and surveillance activities for
      this patient population.

PMID- 12066261
TI  - Father-to-father support: fathers of children with cancer share their experience.
AB  - Fathers are important to the stability of the family and to the coping of mothers
      and their children when there is a child in treatment with cancer. The
      vulnerability they experience is stupefying and causes self-doubt, general worry,
      and frustration with the medical care they receive. Fathers' experiences are
      relatively unreported in the literature, and even less so, the experiences of
      fathers with children who have cancer. This research is based on two focus groups
      of five men each who spoke unabashedly for more than 2 hours about their grief,
      their struggle to come to terms with the diagnosis and the role strain, and role
      confusion they experienced as fathers and husbands. The findings could be
      described as reflecting the following themes: (1) impact on the provider role,
      (2) the emotional impact: I cry privately, (3) it's the fight of our lives, (4)
      tag-team parenting, (5) hypervigilance, (6) that place is scary!, and (7) what
      happens next--coping and moving on. The group format was powerful in terms of
      what these men were willing to share of themselves and their experience. These
      groups could be characterized as the coming together of strangers, bound by the
      common experience of "cancer," who actively supported each other and each other's
      process. Implications for holistic nursing practice are provided.

PMID- 12066262
TI  - Uncertainty, anxiety, and symptoms of posttraumatic stress in parents of children
      recently diagnosed with cancer.
AB  - The purpose of the study was to describe relationships between uncertainty,
      anxiety, and symptoms of posttraumatic stress (PTS) in parents of children
      recently diagnosed with cancer. The study was guided by the Uncertainty in
      Illness Theory. The setting was a children's hospital. Participants were 15
      parents of 12 children recently diagnosed with cancer. Anxiety was measured by
      the State-Trait Anxiety Inventory. Uncertainty was measured by the Parent
      Perception of Uncertainty Scale. Symptoms of PTS were measured by the Reaction
      Index. Total scale scores were calculated and psychometrics estimated.
      Differences in uncertainty, anxiety, and symptoms of PTS by parent race were
      assessed using analysis of variance. The correlation matrix was estimated to
      assess relationships between variables. The level of uncertainty was lower than
      expected, but was significantly higher for black parents (p < .001). The level of
      anxiety was comparable to that for hospitalized persons with anxiety disorders.
      The level of symptoms of PTS was higher than reported for parents of childhood
      cancer survivors. The relationship between anxiety and symptoms of PTS was
      significant (r =.56, p < .02). Pediatric oncology nurses should offer parents
      interventions to relieve high levels of anxiety and symptoms of PTS; some parents
      could also benefit from interventions that target uncertainty.

PMID- 12066263
TI  - Roadmaps: Pediatric hematology/oncology: Day after day...the children make it
      worthwhile.

PMID- 12066264
TI  - How to deliver the word?

PMID- 12066265
TI  - New experience with alumina-on-alumina ceramic bearings for total hip
      arthroplasty.
AB  - A major challenge for total hip arthroplasty is to minimize wear and osteolysis
      in young, active patients. Alumina ceramic bearings have shown superior wear
      resistance and lubrication and do not carry the risk of ion release. In a
      prospective randomized study, 514 hips were implanted. All patients (average age,
      53 years) received the same press-fit hydroxyapatite coated femoral stem; two
      thirds (345 hips) received alumina ceramic bearings, and one third (169 hips)
      received a cobalt-chrome-on-polyethylene bearing. At a mean follow-up of 35.2
      months (range, 24-48 months), there was no significant difference in clinical
      performance between the patient cohorts. No ceramic fracture or alumina ceramic
      bearing failure occurred. This new experience involves the use of improved
      ceramic materials and new design considerations that eliminate the risks and
      complications of past experiences with ceramic implants and provides a safe
      bearing option for young patients.

PMID- 12066266
TI  - Lumbar paravertebral nerve block in the management of pain after total hip and
      knee arthroplasty: a randomized controlled clinical trial.
AB  - The accepted mode of pain management after total hip or knee arthroplasty is
      patient-controlled analgesia. This study evaluates the efficacy of lumbar
      paravertebral nerve block in diminishing postoperative pain when used as an
      adjunct to patient-controlled analgesia. A total of 115 arthroplasty patients
      received postoperatively a lumbar paravertebral nerve block (block, n = 57) or a
      sham procedure (control, n = 58). The block group required approximately 10 mg
      less morphine for pain control than the control group during the first 4 hours
      postoperatively (P<.001). There were no significant differences in morphine use
      between the groups 4 to 24 hours postoperatively. Visual analog scale pain score
      measurements at 4, 8, and 24 hours did not differ significantly between the
      groups. Paravertebral nerve block of the lumbar plexus is an invasive procedure
      with some risk. Considering the added risk and minimal benefits, routine use of
      this procedure is not supported.

PMID- 12066267
TI  - The effect of demineralized bone matrix gel on bone ingrowth and fixation of
      porous implants.
AB  - The presence of demineralized bone matrix (DBM) gel did not enhance or accelerate
      attachment strength or bone ingrowth and resulted in a significant decrease in
      implant interface attachment strength at 3 weeks. Hydroxyapatite (HA) coating
      resulted in significant increases in interface shear strength and bone ingrowth
      compared with non-HA-coated porous implants at all time periods. The HA-coated
      implants achieved greater attachment strength and bone ingrowth at earlier time
      periods and maintained greater attachment strength at long-term periods. The
      results of this study indicate that in the presence of a good bone-implant
      interference fit, there is no beneficial effect in applying DBM gel to a porous
      coated or HA-coated porous implant surface. The small amount that can be applied
      and the degree of osteoinductivity of DBM seem to preclude it from having a
      significant biologic effect.

PMID- 12066268
TI  - Revision of the stiff total knee arthroplasty.
AB  - This study evaluated the improvement in range of motion after revision total knee
      arthroplasty (TKA) in a consecutive series of patients with TKAs presenting with
      pain and limited range of motion. Eleven stiff (range of motion <70 degrees ) and
      painful TKAs were revised with a posterior stabilized condylar prosthesis and
      reviewed after an average of 37.6 months (range, 24-53 months). The average range
      of motion increased from 39.7 degrees preoperatively to 83.2 degrees
      postoperatively. The mean flexion contracture decreased from 13.2 degrees to 0.9
      degrees. Pain scores improved from 4.5 to 44.1, and all 11 patients were
      satisfied. This study shows that knee range of motion can improve significantly
      after revision TKA.

PMID- 12066269
TI  - The effect of total knee arthroplasty design on extensor mechanism function.
AB  - The effect of total knee arthroplasty design on extensor mechanism function was
      evaluated prospectively in a consecutive, single-surgeon series. Group 1 knees (n
      = 83) were implanted with a prosthesis that has a multiradius femoral component,
      and group 2 knees (n = 101) were implanted with a femoral prosthesis that has a
      single flexion-extension axis. Group 2 knees gained flexion more rapidly: At 6
      weeks, the average flexion for was 94.5 degrees for group 1 and 107.1 degrees for
      group 2 (P<.001). Significantly more patients with group 2 knees were able to
      arise from a 16-inch (low) chair without using their arms starting at 6 weeks,
      and a difference was maintained through 2 years (90% vs 73%; P=.003). Patients
      with group 2 knees had significantly less anterior knee pain when rising from a
      seated position starting at 6 weeks, and a difference was maintained through 2
      years (1% vs 22%; P=.001).

PMID- 12066270
TI  - Patellofemoral complications after posterior-stabilized total knee arthroplasty:
      a comparison of 2 different implant designs.
AB  - We conducted a retrospective review of 2 consecutive series of posterior
      stabilized total knee arthroplasties (TKAs) to evaluate patellofemoral
      complications, in particular, significant patellofemoral crepitance or patellar
      clunk syndrome. Twenty posterior-stabilized Axiom PSK (Wright Medical Technology,
      Arlington, TN) TKAs (group 1) were compared with 20 posterior cruciate-sacrificed
      Advance medial pivot (Wright Medical Technology, Arlington, TN) TKAs (group 2).
      The average age in group 1 was 69 years and in group 2 was 70 years. Preoperative
      valgus alignment in group 1 was 7.5 degrees and in group 2 was 1.3 degrees.
      Postoperative valgus alignment for the 2 groups was 4.8 degrees and 5.3 degrees
      valgus. Postoperative patellar tilt for the 2 groups was 0.9 degrees lateral tilt
      and 8 degrees lateral tilt. Patellofemoral signs of crepitance > or =2+ and
      significant box impingement complaints of either snapping or clunking decreased
      significantly postoperatively from 5 of 20 (25%) in group 1 to 0 of 20 in group 2
      (P=.0079).

PMID- 12066271
TI  - Total hip arthroplasty in ankylosing spondylitis: an analysis of 181 hips.
AB  - The results of cemented total hip arthroplasty (THA) in patients with ankylosing
      spondylitis were studied to determine the utility of THA for these patients. A
      total of 103 patients with ankylosing spondylitis underwent 181 THAs; 72 patients
      (69.9%) had bilateral surgery. The mean follow-up was 10.3 years. The mean age of
      patients at surgery was 47 years. Before surgery, 42 hips (23.2%) were ankylosed.
      Revision surgery was carried out in 25 hips (13.8%). Heterotopic ossification was
      present in 21 hips (11.6%); however, no patients had functional impairment or
      reankylosis. At final follow-up examination, 173 hips (96%) had an excellent
      (low) pain score, and 53 hips had a normal or near-normal function score (29.2%).
      The probability of survival of the implant was 71% at 27 years. THA provides long
      term improvement in hip function for patients with ankylosing spondylitis.

PMID- 12066273
TI  - Simultaneous bilateral total hip arthroplasty in sickle cell disease.
AB  - Simultaneous bilateral uncemented total hip arthroplasty for avascular necrosis
      of the femoral head resulting from sickle cell disease was performed in 18
      consecutive patients (36 hips). The patients were followed 2 to 10 years (mean,
      5.7 years). All patients showed improvement in postoperative hip scores compared
      with preoperative scores for pain, range of motion, and function. There were 2
      immediate postoperative complications related to sickling of red blood cells. One
      intraoperative fracture of the proximal femur occurred. There was 1 superficial
      and 1 deep infection. There was no femoral stem loosening, but 1 protrusio
      acetabuli occurred. One acetabular cup was revised for instability. Heterotopic
      ossification developed in 2 patients. Simultaneous bilateral total hip
      arthroplasty in sickle cell disease is a good option in a select group of
      patients with adequate hydration and ventilation in the perioperative and
      postoperative periods.

PMID- 12066272
TI  - Bilateral cemented and cementless total hip arthroplasty.
AB  - A subjective, clinical, and radiographic comparison was made between 140 primary
      cemented and cementless femoral components in 70 patients <50 years old who
      underwent bilateral simultaneous total hip arthroplasty. The average duration of
      follow-up was 7.8 years (range, 7-9 years). Hip scores were similar in both
      groups at the final follow-up. The prevalence of transitory thigh pain was 17% in
      the cementless group and 3% in the cemented group. No hip had subsidence or
      aseptic loosening of the acetabular or femoral components in either group. One
      cemented hip was revised for late infection, and 1 cementless hip was revised for
      recurrent dislocation. There was no difference in the incidence of osteolysis in
      the femur (9% in the cemented hip vs 13% in the cementless hip) and acetabulum
      (9% each) between the groups.

PMID- 12066274
TI  - Venous impulse foot pumps: should graduated compression stockings be used?
AB  - It is not known whether the effect of Foot Pumps (Novamedix, Andover, UK) is
      enhanced by simultaneous use of graduated compression stockings (by controlling
      calf compliance) or hindered (by restricting preload). To address this question,
      we studied 20 healthy volunteers with duplex ultrasound. The peak velocity in the
      popliteal vein was measured at rest with the legs flat, foot-up, and foot-down,
      then it was measured when the AV Impulse Foot Pump was activated. These
      measurements each were performed with and without graduated compression
      stockings. In each leg position, the use of simultaneous graduated compression
      stockings reduced the peak velocity. On physiologic grounds, graduated stockings
      should not be used simultaneously with Foot Pumps.

PMID- 12066275
TI  - Fixation of the NexGen HA-TCP-coated cementless, screwless total knee
      arthroplasty: comparison with conventional cementless total knee arthroplasty of
      the same type.
AB  - We performed a 12-month prospective study on 59 patients (92 knees) who underwent
      NexGen (Zimmer Inc, Warsaw, IN) cruciate-retaining total knee arthroplasty. In
      the control group, uncoated components were fixed using screws, whereas the
      hydroxyapatite-tricalcium phosphate (HA-TCP) group underwent screwless fixation
      of coated components. At 12 months postoperatively, there was a radiographic
      clear zone around the femoral and tibial components of 56.5% and 32.6% of the
      knees in the control group. The HA-TCP group showed a clear zone at the medial
      aspect of the tibial component in only 1 knee. These results suggested that HA
      TCP-coated articular components show good initial fixation without using screws.
      The NexGen coated knee arthroplasty may be useful for solving the problems of
      cementless fixation.

PMID- 12066276
TI  - Patient expectation and satisfaction in revision total hip arthroplasty.
AB  - Sixty-six consecutive revision total hip arthroplasty patients were asked about
      their expectations regarding future pain and walking ability. Expectations were
      high, regardless of background factors: 92% expected to have much less pain, and
      82% expected the same walking ability as after the primary arthroplasty or a much
      improved walking ability. Of the patients, 56% stated a non-surgeon-related
      origin of expectations, 7% were uncertain, and 37% said expectations derived from
      the surgeon. At 1 year, Harris hip score had increased from a median 45 to 77
      points, but only 69% and 55% said that their expectations had been fulfilled to a
      very large or rather large extent regarding pain and walking ability. The only
      predictor of fulfilled expectations was absence of complications (odds ratio,
      4.8; 95% confidence interval, 1.1-20.8). Patient satisfaction was only moderate;
      63% were very or rather satisfied with a moderate correlation (0.46-0.47) between
      satisfaction and fulfilled expectations. Patients with a poor preoperative hip
      condition generally were more satisfied (odds ratio, 5.0; 95% confidence
      interval, 1.4-17.9), and the most important reason probably was an improved
      walking ability (r = 0.64). Patient dissatisfaction may originate from
      unrealistic expectations. At preoperative consultation, it is recommended that
      the surgeon discuss the revision patient's expectations, especially regarding
      future walking ability, and inform the patient about the fundamental prognostic
      differences between revision and primary hip arthroplasty.

PMID- 12066277
TI  - Results of a tapered cementless femoral stem implanted in varus.
AB  - Varus placement of the femoral component in total hip arthroplasty has been
      associated with poor outcomes. The purpose of this study was to examine results
      of total hip arthroplasty with varus alignment of a tapered titanium femoral
      prosthesis (Alloclassic; Sulzer, Zurich, Switzerland) at a minimum 5-year follow
      up. Of a consecutive series of 585 patients, 23 met the inclusion criteria.
      Harris hip scores averaged 97, and all implants were clinically and
      radiographically stable at the most recent follow-up. In this series of patients,
      varus alignment of the prosthesis did not have an adverse effect on outcome.
      Although malalignment of the femoral prosthesis may compromise the results of
      some designs, the Alloclassic prosthesis has proved to be reliable and forgiving
      despite varus malalignment at 5 to 11 years' follow-up.

PMID- 12066278
TI  - In vitro kinematic patterns are similar for a fixed platform and a mobile bearing
      prosthesis.
AB  - In vitro dynamic simulation of knee flexion was performed to quantify knee
      kinematics for a mobile bearing prosthesis that allows the tibial insert to
      translate and rotate with respect to the baseplate. Six cadaver knees were tested
      in the intact state, after implanting a fixed platform prosthesis, and after
      implanting a mobile bearing prosthesis. The mobile bearing prosthesis
      significantly increased the tibial internal rotation and medial shift compared
      with the intact knee, near 90 degrees of flexion. Both prostheses increased the
      patellar medial shift near 90 degrees of flexion. The patellar flexion was
      significantly larger for the mobile bearing prosthesis than for the fixed
      platform prosthesis for most of flexion. Motion of the insert with respect to the
      baseplate may have contributed to the variations in tibiofemoral kinematics,
      whereas tibiofemoral kinematic changes influenced the patellofemoral kinematics.
      Although the kinematics were similar for the 2 types of prosthesis, the
      possibility of complications related to increased patellar flexion and backside
      wear of the tibial insert should be considered.

PMID- 12066279
TI  - In vitro evaluation of the resistance to dislocation of a meniscal-bearing total
      knee prosthesis between 30 degrees and 90 degrees of knee flexion.
AB  - An increased incidence of dislocation is the most important potential
      disadvantage introduced by the use of meniscal-bearing prostheses. The aim of
      this in vitro study was to measure the resistance to dislocation of a meniscal
      bearing total knee arthroplasty in various circumstances and to establish which
      anatomic structures contribute to bearing stability. The prosthesis was implanted
      into cadaver knee specimens mounted in a 6 df rig. Dislocation was provoked by
      applying anteriorly or posteriorly directed forces (20-100N) to the tibia in the
      plane of the tibial plateau. Dislocation was defined as any stable displacement
      of the bearing (relative to the tibia or the femur) that persisted after release
      of the load applied to provoke it. The specimens were tested in an arc of knee
      flexion between 30 degrees and 90 degrees, with and without simulated quadriceps
      loads, with and without abducting and adducting loads, and before and after
      division of the posterior cruciate ligament and the lateral retinaculum. In the
      presence of quadriceps load, dislocation could not be provoked. In the absence of
      quadriceps load, dislocation was not provoked by posteriorly directed force but
      sometimes was caused by anteriorly directed force. All but 1 of the dislocations
      were unicompartmental, the lateral compartment proving much less stable than the
      medial. The tendency toward dislocation increased from 30 degrees to 60 degrees
      and from 60 degrees to 90 degrees of knee flexion. Adducting moments applied to
      the knee caused lift-off of the lateral femoral condyle from the bearing and
      increased the tendency toward dislocation. Abducting moments had the opposite
      effect. Division of the posterior cruciate ligament had no significant effect.
      Division of the lateral retinaculum increased the tendency toward dislocation. A
      femoral component that can be implanted without lateral release is desirable.

PMID- 12066280
TI  - The function of the posterior cruciate ligament in an anteroposterior-gliding
      rotating platform total knee arthroplasty.
AB  - Knee kinematics after total knee arthroplasty is dictated primarily by implant
      geometry and native soft tissue constraints. This study highlights the importance
      of a functioning posterior cruciate ligament in limiting excessive
      anteroposterior translation in a mobile bearing knee design that relies on native
      posterior cruciate ligament integrity and postarthroplasty tensioning for
      stability rather than any inherent mechanical design stability, such as anterior
      rails or stops.

PMID- 12066281
TI  - Accurate in vivo measurement of polyethylene wear in total knee arthroplasty.
AB  - This study describes a new technique to evaluate accurate linear polyethylene
      wear and reports the in vivo annual linear wear rate in total knee arthroplasty.
      Patients (n = 69) were assessed using a single standing anteroposterior
      radiograph with 8 reference markers around the knee, where 3-dimensional (3D)
      locations of markers and 3D geometry of the implant were known. By matching the
      3D locations of the markers and their projected points on the radiograph, 3D/2D
      transformation parameters were estimated. Using these parameters, the 3D
      coordinates of the implant were estimated from the projected x-ray silhouette.
      After calculating the femorotibial shortest distance, wear and creep deformity of
      the polyethylene was defined with an accuracy of 0.1 mm or better. Measured
      linear wear in the 69 knees varied from 0 mm (1 month postoperatively) to 2.71 mm
      (7 years postoperatively). The correlation of linear wear (Y) and year (X) was Y
      = 0.23 X -0.11 (P<.001). This study revealed that annual wear rate was 0.23 mm
      and 2 times greater than the average annual wear rate in total hip
      arthroplasties.

PMID- 12066282
TI  - Protection of femoral neck taper in revision of acetabular component.
AB  - In hip revision restricted to the acetabular component, the taper of a modular
      stem is in constant danger of scratching. We used a plastic syringe to protect
      the taper of the femoral component. A plastic syringe of appropriate size remains
      well in place and offers a novel and inexpensive protective device for the taper
      of the femoral component available in every operation room.

PMID- 12066283
TI  - Lumbar plexus block with perineural catheter and sciatic nerve block for total
      hip arthroplasty.
AB  - This case series describes the use of continuous lumbar plexus block with sciatic
      nerve block as an alternative anesthetic for total hip arthroplasty (THA). A
      retrospective chart review was performed on 10 consecutive patients who underwent
      THA at Walter Reed Army Medical Center using continuous lumbar plexus block and
      sciatic nerve block for anesthesia. Continuous lumbar plexus block with sciatic
      nerve block without concurrent general anesthesia has not been described
      previously for THA. Peripheral nerve block may provide superior intraoperative
      outcomes, as suggested by lower operative blood loss and potentially lower
      transfusion exposure. Lumbar plexus block with perineural catheter and sciatic
      nerve block with perioperative sedation is an effective alternative to general
      anesthesia for THA.

PMID- 12066284
TI  - Delayed fracture of the ceramic femoral head after trauma.
AB  - There are various ways in which a total hip arthroplasty may fail
      catastrophically. Failure of the ceramic femoral head component is well known and
      described. It may fail because of trauma, but delayed fracture after trauma has
      not been described previously. This case report describes this phenomenon and
      postulates a possible mechanism for this failure.

PMID- 12066285
TI  - Retrograde injection of a nutrient vein with cement in cemented total hip
      arthroplasty.
AB  - An 80-year-old woman received a cemented total hip arthroplasty. The surgery was
      performed without intraoperative complications. Postoperative radiographs and a
      computed tomography scan revealed a nutrient vein perforating the femur, which
      was retrogradely filled with cement. An abdominal and thoracic computed
      tomography scan showed no further dissemination of cement.

PMID- 12066286
TI  - Locking mechanism failure in the Harris-Galante porous acetabular component
      associated with recurrent hip dislocation.
AB  - In this review of longitudinal studies of the Harris-Galante porous acetabular
      component, 20% of all revisions were caused by failure of the polyethylene liner
      locking mechanism. We report 2 cases of locking mechanism failure in the Harris
      Galante porous acetabular component presenting with recurrent dislocation. Broken
      tines from the acetabular locking mechanism were found embedded into the
      polyethylene liners in both cases. In a 79-year-old woman with recurrent
      dislocation, the polyethylene liner and femoral head were replaced, and the
      acetabular component was revised. In a 74-year-old man with chronic recurrent
      dislocation, the polyethylene liner and femoral head were replaced, but the
      acetabular component was preserved. Appropriate treatment for locking mechanism
      failure with a well-fixed acetabular component depends on many factors, and
      further long-term data are needed.

PMID- 12066287
TI  - Femoral neuropathy caused by reinforcement ring malposition and extruded bone
      cement after revision total hip arthroplasty.
AB  - Femoral neuropathy occurred after revision total hip arthroplasty as a result of
      pressure from the reinforcement ring and extruded bone-cement (polymethyl
      methacrylate). Four weeks after the revision surgery, we performed an operation
      to decompress the femoral nerve and allow neurolysis. Neuropathy improved
      gradually after the subsequent surgery.

PMID- 12066288
TI  - Aseptic loosening of 2 rim-fix, hydroxyapatite-coated acetabular cups.
AB  - Two cases of aseptic loosening in the 11th and 12th year of follow-up of the same
      acetabular component of a fully hydroxyapatite (HA)-coated total hip arthroplasty
      are presented. The acetabular cup was a rim-fix type, HA-coated, titanium
      hemispherical shell secured to the bony acetabulum with titanium screws at the
      peripheral polyethylene rim. The short-term and midterm results were good with HA
      coated total hip arthroplasties, but further studies are needed to investigate
      whether the >10-year survival of these cups is as good as the survival of
      cemented ones.

PMID- 12066289
TI  - Posterior femoral impingement causing polyethylene failure in total knee
      arthroplasty.
AB  - Several reports in the literature describe dislocation and fractures of the
      meniscal bearings as a result of polyethylene failure after total knee
      arthroplasty. In this case of an asymptomatic patient with a clinically
      uneventful 7-year follow-up, who died a year later of an unrelated cause, we
      found impressive damage of the polyethylene components. This damage, at the
      posterior corner of the meniscal bearing elements, was caused by regrowth of the
      posterior femoral osteophytes. The primary osteophytes had been resected
      adequately during the arthroplasty. These osteophytes are related to a bone
      polyethylene impingement that occurs at >110 degrees of knee flexion. The
      possible range of motion of an artificial joint, owing to its design, is less
      than the range of flexion sometimes reached clinically by the patient. This is a
      problem that should be solved by the industry in the near future.

PMID- 12066290
TI  - More characters or more taxa for a robust phylogeny--case study from the coffee
      family (Rubiaceae).
AB  - Using different data sets mainly from the plant family Rubiaceae, but in parts
      also from the Apocynaceae, Asteraceae, Lardizabalaceae, Saxifragaceae, and
      Solanaceae, we have investigated the effect of number of characters, number of
      taxa, and kind of data on bootstrap values within phylogenetic trees. The
      percentage of supported nodes within a tree is positively correlated with the
      number of characters, and negatively correlated with the number of taxa. The
      morphological analyses are based on few characters and weakly supported trees are
      expected. The percentage of supported nodes is also dependent on the kind of data
      analyzed. In analyses of Rubiaceae based on the same number of characters, RFLP
      data give trees with higher percentage of supported nodes than rbcL and
      morphological data. We also discuss the support values for particular nodes at
      the familial and subfamilial levels. Two new data sets of ndhF and rbcL sequences
      of Rubiaceae are analyzed and together with earlier studies of the family we can
      conclude that the monophyly of the Rubiaceae is supported and within the family
      there are three well supported, but not easily characterized, large subfamilies,
      Rubioideae, Cinchonoideae s.s. and Ixoroideae s.l. There are also a few genera
      (Luculia and Coptosapelta) unclassified to subfamily.

PMID- 12066291
TI  - The position of Cetacea within mammalia: phylogenetic analysis of morphological
      data from extinct and extant taxa.
AB  - Knowledge of the phylogenetic position of the order Cetacea (whales, dolphins,
      and porpoises) within Mammalia is of central importance to evolutionary
      biologists studying the transformations of biological form and function that
      accompanied the shift from fully terrestrial to fully aquatic life in this clade.
      Phylogenies based on molecular data and those based on morphological data both
      place cetaceans among ungulates but are incongruent in other respects.
      Morphologists argue that cetaceans are most closely related to mesonychians, an
      extinct group of terrestrial ungulates. They have disagreed, however, as to
      whether Perissodactyla (odd-toed ungulates) or Artiodactyla (even-toed ungulates)
      is the extant clade most closely related to Cetacea, and have long maintained
      that each of these orders is monophyletic. The great majority of molecule-based
      phylogenies show, by contrast, not only that artiodactyls are the closest extant
      relatives of Cetacea, but also that Artiodactyla is paraphyletic unless cetaceans
      are nested within it, often as the sister group of hippopotamids. We tested
      morphological evidence for several hypotheses concerning the sister taxon
      relationships of Cetacea in a maximum parsimony analysis of 123 morphological
      characters from 10 extant and 30 extinct taxa. We advocate treating certain
      multistate characters as ordered because such a procedure incorporates
      information about hierarchical morphological transformation. In all most
      parsimonious trees, whether multistate characters are ordered or unordered,
      Artiodactyla is the extant sister taxon of Cetacea. With certain multistate
      characters ordered, the extinct clade Mesonychia (Mesonychidae + Hapalodectidae)
      is the sister taxon of Cetacea, and Artiodactyla is monophyletic. When all
      fossils are removed from the analysis, Artiodactyla is paraphyletic with Cetacea
      nested inside, indicating that inclusion of mesonychians and other extinct stem
      taxa in a phylogenetic analysis of the ungulate clade is integral to the recovery
      of artiodactyl monophyly. Phylogenies derived from molecular data alone may risk
      recovering inconsistent branches because of an inability to sample extinct
      clades, which by a conservative estimate, amount to 89% of the ingroup. Addition
      of data from recently described astragali attributed to cetaceans does not
      overturn artiodactyl monophyly.

PMID- 12066292
TI  - Primates and their pinworm parasites: the cameron hypothesis revisited.
AB  - A morphologically based cladistic analysis of the Enterobiinae, which includes
      most of the Oxyuridae parasitic in Primates, allows a reevaluation of the
      Cameron's hypothesis of close coevolution with cospeciation between hosts and
      parasites. Each of the three genera separated in the Enterobiinae fits with one
      of the suborders defined in Primates: Lemuricola with the Strepsirhini,
      Trypanoxyuris with the Platyrrhini, and Enterobius with the Catarrhini. Inside
      each of the three main groups, the subdivisions observed in the parasite tree
      also fit with many of the subdivisions generally accepted within the Primate
      order. These results confirm the subgroups previously described in the subfamily
      and support Cameron's hypothesis in its aspect of association by descent.
      Although the classification of the Enterobiinae generally closely underlines the
      classification of Primates, several discordances also are observed. These are
      discussed case by case, with use of computed reconstruction scenarios. Given that
      the occurrences of the same pinworm species as a parasite for several congeneric
      host species is not the generalized pattern, and given that several occurrences
      also are observed in which the speciations of the parasites describe a more
      complex network, Cameron's hypothesis of a slower rhythm of speciation in the
      parasites can be considered partly refuted. The presence of two genera parasitic
      on squirrels in a family that contains primarily primate parasites also is
      discussed. The cladistic analysis does not support close relationships between
      the squirrel parasites and suggests an early separation from the Enterobiinae for
      the first (Xeroxyuris), and a tardy host-switching from the Platyrrhini to the
      squirrels for the second (Rodentoxyuris).

PMID- 12066293
TI  - Polytomies and phylogenetically independent contrasts: examination of the bounded
      degrees of freedom approach.
AB  - We examined the effect of soft polytomies on the performance (Type I error rate
      and bias) of Felsenstein's (1985; Am. Nat. 125:1-15) method of phylogenetically
      independent contrasts for estimating a bivariate correlation. We specifically
      tested the adequacy of bounding degrees of freedom, as suggested by Purvis and
      Garland (1993; Syst. Biol. 42:569-575). We simulated bivariate character
      evolution under Brownian motion (assumed by independent contrasts) and eight
      other models on five phylogenetic trees. For non-Brownian motion simulations, the
      adequacy of branch-length standardization was checked with a simple diagnostic
      (Garland et al., 1992; Syst. Biol. 41:18-32), and transformations were applied as
      indicated. Surprisingly, soft polytomies tended to have negligible effects on
      Type I error rates when models other than Brownian motion were used. Overall, and
      irrespective of evolutionary model, degrees of freedom were appropriately bounded
      for hypothesis testing, and unbiased estimates of the correlation coefficient
      were obtained. Our results, along with those of previous simulation studies,
      suggest that independent contrasts can reliably be applied to real data, even
      with phylogenetic uncertainty.

PMID- 12066294
TI  - Assessing congruence between cladistic and stratigraphic data.

PMID- 12066295
TI  - Sampling confidence envelopes of phylogenetic trees for combinability testing: a
      reply to Rodrigo.

PMID- 12066296
TI  - Data set incongruence and correlated character evolution: an example of
      functional convergence in the hind-limbs of stifftail diving ducks.
AB  - The unwitting inclusion of convergent characters in phylogenetic estimates poses
      a serious problem for efforts to recover phylogeny. Convergence is not
      inscrutable, however, particularly when one group of characters tracks phylogeny
      and another set tracks adaptive history. In such cases, convergent characters may
      be correlated with one or a few functional anatomical units and readily
      identifiable by using comparative methods. Stifftail ducks (Oxyurinae) offer one
      such opportunity to study correlated character evolution and function in the
      context of phylogenetic reconstruction. Morphological analyses place stifftail
      ducks as part of a large clade of diving ducks that includes the sea ducks
      (Mergini), Hymenolaimus, Merganetta, and Tachyeres, and possibly the pochards
      (Aythyini). Molecular analyses, on the other hand, place stifftails far from
      other diving ducks and suggest, moreover, that stifftails are polyphyletic.
      Mitochondrial cytochrome b gene sequences of eight stifftail species
      traditionally supposed to form a clade were compared with each other and with
      sequences from 50 other anseriform and galliform species. Stifftail ducks are not
      the sister group of sea ducks but lie outside the typical ducks (Anatinae). Of
      the four traditional stifftail genera, monophyly of Oxyura and its sister group
      relationship with Nomonyx are strongly supported. Heteronetta probably is the
      sister group of that clade, but support is weak. Biziura is not a true stifftail.
      Within Oxyura, Old World species (O. australis, O. leucocephala, O. maccoa)
      appear to form a clade, with New World species (O. jamaicensis, O. vittata)
      branching basally. Incongruence between molecules and morphology is interpreted
      to be the result of adaptive specialization and functional convergence in the
      hind limbs of Biziura and true stifftails. When morphological characters are
      divided into classes, only hind-limb characters are significantly in conflict
      with the molecular tree. Likewise, null models of synonymous and nonsynonymous
      substitution based on patterns of codon-degeneracy and chemical dissimilarity
      indicate that the nucleotide and amino acid changes postulated by the molecular
      tree are more plausible than those postulated by the morphological tree. These
      findings teach general lessons about the utility of highly adaptive characters
      (in particular those related to foraging ecology) and underscore the problems
      that convergence can pose for attempts to recover phylogeny. They also
      demonstrate how the concept of natural data partitions and simple models of
      evolution (e.g., parsimony, likelihood, neutrality) can be used to test the
      accuracy of independent phylogenetic estimates and provide arguments in favor of
      one tree topology over another.

PMID- 12066297
TI  - Molecular phylogeny of the marmots (Rodentia: Sciuridae): tests of evolutionary
      and biogeographic hypotheses.
AB  - There are 14 species of marmots distributed across the Holarctic, and despite
      extensive systematic study, their phylogenetic relationships remain largely
      unresolved. In particular, comprehensive studies have been lacking. A well
      supported phylogeny is needed to place the numerous ecological and behavioral
      studies on marmots in an evolutionary context. To address this situation, we
      obtained complete cytochrome (cyt) b sequences for 13 of the species and a
      partial sequence for the 14th. We applied a statistical approach to both
      phylogeny estimation and hypothesis testing, using parsimony and maximum
      likelihood-based methods. We conducted statistical tests on a suite of previously
      proposed hypotheses of phylogenetic relationships and biogeographic histories.
      The cyt b data strongly support the monophyly of Marmota and a western montane
      clade in the Nearctic. Although some other scenarios cannot be rejected, the
      results are consistent with an initial diversification in North America, followed
      by an invasion and subsequent rapid diversification in the Palearctic. These
      analyses reject the two major competing hypotheses of M. broweri's phylogenetic
      relationships--namely, that it is the sister species to M. camtschatica of
      eastern Siberia, and that it is related closely to M. caligata of the Nearctic.
      The Alaskan distribution of M. broweri is best explained as a reinvasion from the
      Palearctic, but a Nearctic origin can not be rejected. Several other
      conventionally recognized species groups can also be rejected. Social evolution
      has been homoplastic, with large colonial systems evolving in two groups
      convergently. The cyt b data do not provide unambiguous resolution of several
      basal nodes in the Palearctic radiation, leaving some aspects of pelage and
      karyotypic evolution equivocal.

PMID- 12066298
TI  - Molecular evidence for the compilospecies model of reticulate evolution in
      Armeria (Plumbaginaceae).
AB  - Cladistic analyses of the nuclear ribosomal DNA (nrDNA) internal transcribed
      spacer (ITS) sequences from 55 samples corresponding to 34 taxa in the genus
      Armeria reveal that ITS sequence diversity among and within species utterly
      conflicts with patterns of morphological similarity. Three facts are apparent
      from the results here reported: (1) different samples of a single subspecies, A.
      villosa subsp. longiaristata, appear in three of the five major clades; (2)
      samples of at least one of the six subspecies of A. villosa appear in four of the
      five major clades; and (3) the composition of major clades shows greater
      congruence with the geographic origin of plants than with the traditional
      systematic arrangement based primarily on morphology. Specifically, the clades
      here termed Ia, II, III, and IV each encompass terminals restricted to
      geographically delimited areas. There are alternative explanations for the ITS
      pattern, but the most likely one is that nucleotide positions supporting the
      major clades are due, in some of the samples, to concerted evolution following
      horizontal transfer (gene flow) rather than to recency of common ancestry. This
      interpretation is consistent with previous systematic and experimental evidence
      and implies that reticulation in Armeria may be extensive. Harlan and de Wet
      (1963, Evolution 17:497-501) proposed the compilospecies concept to account for
      situations in which a genetically "aggressive" species captures portions of the
      genome of other sympatric species by means of extensive introgression. Evidence
      of extensive reticulation, ecological diversification, and geographic pattern
      indicates that A. villosa may fit the compilospecies concept, which is here
      supported on molecular grounds for the first time.

PMID- 12066299
TI  - Species names in phylogenetic nomenclature.
AB  - Linnaean binomial nomenclature is logically incompatible with the phylogenetic
      nomenclature of de Queiroz and Gauthier (1992, Annu. Rev. Ecol. Syst. 23:449
      480): The former is based on the concept of genus, thus making this rank
      mandatory, while the latter is based on phylogenetic definitions and requires the
      abandonment of mandatory ranks. Thus, if species are to receive names under
      phylogenetic nomenclature, a different method must be devised to name them. Here,
      13 methods for naming species in the context of phylogenetic nomenclature are
      contrasted with each other and with Linnaean binomials. A fundamental dichotomy
      among the proposed methods distinguishes those that retain the entire binomial of
      a preexisting species name from those that retain only the specific epithet.
      Other relevant issues include the stability, uniqueness, and ease of
      pronunciation of species names; their capacity to convey phylogenetic
      information; and the distinguishability of species names that are governed by a
      code of phylogenetic nomenclature both from clade names and from species names
      governed by the current codes. No method is ideal. Each has advantages and
      drawbacks, and preference for one option over another will be influenced by one's
      evaluation of the relative importance of the pros and cons for each. Moreover,
      sometimes the same feature is viewed as an advantage by some and a drawback by
      others. Nevertheless, all of the proposed methods for naming species in the
      context of phylogenetic nomenclature provide names that are more stable than
      Linnaean binomials.

PMID- 12066300
TI  - How should species phylogenies be inferred from sequence data?

PMID- 12066301
TI  - Phylogenetic congruence and discordance among one morphological and three
      molecular data sets from Pontederiaceae.
AB  - A morphological data set and three sources of data from the chloroplast genome
      (two genes and a restriction site survey) were used to reconstruct the
      phylogenetic history of the pickerelweed family Pontederiaceae. The chloroplast
      data converged towards a single tree, presumably the true chloroplast phylogeny
      of the family. Unrooted trees estimated from each of the three chloroplast data
      sets were identical or extremely similar in shape to each other and mostly
      robustly supported. There was no evidence of significant heterogeneity among the
      data sets, and the few topological differences seen among unrooted trees from
      each chloroplast data set are probably artifacts of sampling error on short
      branches. Despite well-documented differences in rates of evolution for different
      characters in individual data sets, equally weighted parsimony permits accurate
      reconstructions of chloroplast relationships in Pontederiaceae. A separate
      morphology-based data set yielded trees that were very different from the
      chloroplast trees. Although there was substantial support from the morphological
      evidence for several major clades supported by chloroplast trees, most of the
      conflicting phylogenetic structure on the morphology trees was not robust.
      Nonetheless, several statistical tests of incongruence indicate significant
      heterogeneity between molecules and morphology. The source of this apparent
      incongruence appears to be a low ratio of phylogenetic signal to noise in the
      morphological data.

PMID- 12066303
TI  - Step matrices and the interpretation of homoplasy.
AB  - Assumptions about the costs of character change, coded in the form of a step
      matrix, determine most-parsimonious inferences of character evolution on
      phylogenies. We present a graphical approach to exploring the relationship
      between cost assumptions and evolutionary inferences from character data. The
      number of gains and losses of a binary trait on a phylogeny can be plotted over a
      range of cost assumptions, to reveal the inflection point at which there is a
      switch from more gains to more losses and the point at which all changes are
      inferred to be in one direction or the other. Phylogenetic structure in the data,
      the tree shape, and the relative frequency of states among the taxa influence the
      shape of such graphs and complicate the interpretation of possible permutation
      based tests for directionality of change. The costs at which the most
      parsimonious state of each internal node switches from one state to another can
      also be quantified by iterative ancestral-state reconstruction over a range of
      costs. This procedure helps identify the most robust inferences of change in each
      direction, which should be of use in designing comparative studies.

PMID- 12066302
TI  - Combining data sets with different phylogenetic histories.
AB  - The possibility that two data sets may have different underlying phylogenetic
      histories (such as gene trees that deviate from species trees) has become an
      important argument against combining data in phylogenetic analysis. However, two
      data sets sampled for a large number of taxa may differ in only part of their
      histories. This is a realistic scenario and one in which the relative advantages
      of combined, separate, and consensus analysis become much less clear. I propose a
      simple methodology for dealing with this situation that involves (1) partitioning
      the available data to maximize detection of different histories, (2) performing
      separate analyses of the data sets, and (3) combining the data but considering
      questionable or unresolved those parts of the combined tree that are strongly
      contested in the separate analyses (and which therefore may have different
      histories) until a majority of unlinked data sets support one resolution over
      another. In support of this methodology, computer simulations suggest that (1)
      the accuracy of combined analysis for recovering the true species phylogeny may
      exceed that of either of two separately analyzed data sets under some conditions,
      particularly when the mismatch between phylogenetic histories is small and the
      estimates of the underlying histories are imperfect (few characters, high
      homoplasy, or both) and (2) combined analysis provides a poor estimate of the
      species tree in areas of the phylogenies with different histories but gives an
      improved estimate in regions that share the same history. Thus, when there is a
      localized mismatch between the histories of two data sets, the separate,
      consensus, and combined analyses may all give unsatisfactory results in certain
      parts of the phylogeny. Similarly, approaches that allow data combination only
      after a global test of heterogeneity will suffer from the potential failings of
      either separate or combined analysis, depending on the outcome of the test.
      Excision of conflicting taxa is also problematic, in that doing so may obfuscate
      the position of conflicting taxa within a larger tree, even when their placement
      is congruent between data sets. Application of the proposed methodology to
      molecular and morphological data sets for Sceloporus lizards is discussed.

PMID- 12066304
TI  - Can weighting improve bushy trees? Models of cytochrome b evolution and the
      molecular systematics of pipits and wagtails (Aves: Motacillidae).
AB  - Among-site rate variation (alpha) and transition bias (kappa) have been shown,
      most often as independent parameters, to be important dynamics in DNA evolution.
      Accounting for these dynamics should result in better estimates of phylogenetic
      relationships. To test this idea, we simultaneously estimated overall (averaged
      over all codon positions) and codon-specific values of alpha and kappa, using
      maximum likelihood analyses of cytochrome b data from all genera of pipits and
      wagtails (Aves: Motacillidae), and six outgroup species, using initial trees
      generated with default values. Estimates of alpha and kappa were robust to
      initial tree topology and suggested substantial among-site rate variation even
      within codon classes; alpha was lowest (large among-site rate variation) at
      second-codon and highest (low among-site rate variation) at third-codon
      positions. When overall values were applied, there were shifts in tree topology
      and dramatic and statistically significant improvements in log-likelihood scores
      of trees compared with the scores from application of default values. Applying
      codon-specific values resulted in yet another highly significant increase in
      likelihood. However, although incorporating substitution dynamics into maximum
      likelihood, maximum parsimony, and neighbor-joining analyses resulted in
      increases in congruence among trees, there were only minor improvements in
      phylogenetic signal, and none of the successive approximations tree topologies
      were statistically distinguishable from one another by the data. We suggest that
      the bushlike nature of many higher-level phylogenies in birds makes estimating
      the dynamics of DNA evolution less sensitive to tree topology but also less
      susceptible to improvement via weighting.

PMID- 12066305
TI  - Measuring the phylogenetic randomness of biological data sets.
AB  - Two qualitative taxonomic characters are potentially compatible if the states of
      each can be ordered into a character state tree in such a way that the two
      resulting character state trees are compatible. The number of potentially
      compatible pairs (NPCP) of qualitative characters from a data set may be
      considered to be a measure of its phylogenetic randomness. The value of NPCP
      depends on the number of evolutionary units (EUs), the number of characters, the
      number of states in the characters, the distributions of EUs among these states,
      and the amount and distribution of missing information and so does not directly
      indicate degree of phylogenetic randomness. Thus, for an observed data set, we
      used Monte Carlo methods to estimate the probability that a data set chosen
      equiprobably from among those identical (with respect to all the other above
      determining features) to the observed data set would have as high (or low) an
      NPCP as the observed data set. This probability, the realized significance of the
      observed NPCP, is attractive as an indication of phylogenetic randomness because
      it does not require the assumptions made by other such methods: No character
      state trees are assumed and consequently, only potential compatibility can be
      determined; no particular method of phylogenetic estimation is assumed; and no
      phylogenetic trees are constructed. We determined the values and significances of
      NPCP for analyses of 57 data sets taken from 53 published sources. All data sets
      from 37 of those sources exhibited realized significances of < 0.01, indicating
      high levels of phylogenetic nonrandomness. From each of the remaining 16 sources,
      at least one data set was more phylogenetically random. Inclusion of outgroups
      changed significance in some cases, but not always in the same direction. Data
      sets with significantly low NPCP may be consistent with an ancient hybrid origin
      (or other ancient polyphyletic gene exchange, crossing over, viral transfer,
      etc.) of the study group.

PMID- 12066306
TI  - Using a nonrecursive formula to determine cladogram probabilities.
AB  - Three properties of bifurcating branching diagrams that are used for representing
      a specific number of taxa are (1) the number of possible arrangements, (2) the
      number of possible topologies, and (3) the probabilities of formation according
      to particular models of cladogenesis. Of these, the probabilities have received
      the least attention in the literature. Indeed, many biologists would be
      astonished by the observation that the probability of a commonly cited cladogram
      containing 35 phyla of the animal kingdom is < 0.0072% of the value of the
      average probability taken over all possible cladograms! We reviewed works on
      cladogram arrangements and topologies and developed a computer-generated table of
      enumerations that extends and corrects such tables in the literature. We also
      developed a nonrecursive formula for the determination of cladogram
      probabilities. This formula facilitates calculation and thereby should promote
      use of cladogram probabilities, which might provide more accurate null hypotheses
      for tests of cladogenic events than do considerations of cladogram arrangements
      or topologies.

PMID- 12066307
TI  - Does adding characters with missing data increase or decrease phylogenetic
      accuracy?
AB  - Missing data are a widely recognized nuisance factor in phylogenetic analyses,
      and the fear of missing data may deter systematists from including characters
      that are highly incomplete. In this paper, I used simulations to explore the
      consequences of including sets of characters that contain missing data. More
      specifically, I tested whether the benefits of increasing the number of
      characters outweigh the costs of adding missing data cells to a matrix. The
      results show that the addition of a set of characters with missing data is
      generally more likely to increase phylogenetic accuracy than decrease it, but the
      potential benefits of adding these characters quickly disappear as the proportion
      of missing data increases. Furthermore, despite the overall trend, adding
      characters with missing data does decrease accuracy in some cases. In these
      situations, the missing data entries are not themselves misleading, but their
      presence may mimic the effects of limited taxon sampling, which can positively
      mislead. Criteria are discussed for predicting whether adding characters with
      missing data may increase or decrease accuracy. The results of this study also
      suggest that accuracy can be increased to a surprising degree by (1) "filling the
      holes" in a data matrix as much as possible (even when relatively few taxa are
      missing data), and (2) adding fewer characters scored for all taxa rather than
      adding a larger number of characters known for fewer taxa. Missing data can also
      be eliminated from an analysis through the exclusion of incomplete taxa rather
      than incomplete characters, but this approach may reduce the usefulness of the
      analysis and (in some cases) the accuracy of the estimated trees.

PMID- 12066308
TI  - Individuality and the existence of species through time.
AB  - The individuality of species provides the basis for linking practical taxonomy
      with evolutionary and ecological theory. An individual is here defined as a
      collection of parts (lower-level entities) that are mutually connected. Different
      types of species individual exist, based on different types of connection between
      organisms. An interbreeding species is a group of organisms connected by the
      potential to share common descendants, whereas a genealogical species is
      integrated by the sharing of common ancestors. Such species definitions serve to
      set the limits of species at a moment of time and these slices connect through
      time to form time-extended lineages. This perspective on the nature of
      individuality has implications that conflict with traditional views of species
      and lineages: (1) Several types of connections among organisms may serve to
      individuate species in parallel (species pluralism); (2) each kind of species
      corresponds to a distinct kind of lineage; (3) although lineage branching is the
      most obvious criterion to break lineages into diachronic species, it cannot be
      justified simply by reference to species individuality; (4) species (like other
      individuals) have fuzzy boundaries; (5) if we wish to retain a species rank, we
      should focus on either the most- or least-inclusive individual in a nested
      series; (6) not all organisms will be in any species; and (7) named species taxa
      are best interpreted as hypotheses of real species. Although species
      individuality requires significant changes to systematic practice and challenges
      some preconceptions we may have about the ontology of species, it provides the
      only sound basis for asserting that species exist independently of human
      perception.

PMID- 12066309
TI  - Effects of branch length errors on the performance of phylogenetically
      independent contrasts.
AB  - We examined Type I error rates of Felsenstein's (1985; Am. Nat. 125:1-15)
      comparative method of phylogenetically independent contrasts when branch lengths
      are in error and the model of evolution is not Brownian motion. We used seven
      evolutionary models, six of which depart strongly from Brownian motion, to
      simulate the evolution of two continuously valued characters along two different
      phylogenies (15 and 49 species). First, we examined the performance of
      independent contrasts when branch lengths are distorted systematically, for
      example, by taking the square root of each branch segment. These distortions
      often caused inflated Type I error rates, but performance was almost always
      restored when branch length transformations were used. Next, we investigated
      effects of random errors in branch lengths. After the data were simulated, we
      added errors to the branch lengths and then used the altered phylogenies to
      estimate character correlations. Errors in the branches could be of two types:
      fixed, where branch lengths are either shortened or lengthened by a fixed
      fraction; or variable, where the error is a normal variate with mean zero and the
      variance is scaled to the length of the branch (so that expected error relative
      to branch length is constant for the whole tree). Thus, the error added is
      unrelated to the microevolutionary model. Without branch length checks and
      transformations, independent contrasts tended to yield extremely inflated and
      highly variable Type I error rates. Type I error rates were reduced, however,
      when branch lengths were checked and transformed as proposed by Garland et al.
      (1992; Syst. Biol. 41:18-32), and almost never exceeded twice the nominal P-value
      at alpha = 0.05. Our results also indicate that, if branch length transformations
      are applied, then the appropriate degrees of freedom for testing the significance
      of a correlation coefficient should, in general, be reduced to account for
      estimation of the best branch length transformation. These results extend those
      reported in Diaz-Uriarte and Garland (1996; Syst. Biol. 45:27-47), and show that,
      even with errors in branch lengths and evolutionary models different from
      Brownian motion, independent contrasts are a robust method for testing hypotheses
      of correlated evolution.

PMID- 12066310
TI  - Split support and split conflict randomization tests in phylogenetic inference.
AB  - Randomization tests allow the formulation and statistical testing of null
      hypotheses about the quality of entire data sets or the quality of fit between
      the data and particular phylogenetic hypotheses. Randomization tests of
      phylogenetic hypotheses based on the concepts of split support and split conflict
      are described here, as are tests where splits, rather than the data, are randomly
      permuted. These tree-independent randomization tests are explored through their
      application to phylogenetic data for caecilian amphibians. Of these tests, split
      support randomization tests appear to be the most promising tools for
      phylogeneticists. These tests seem quite conservative, are applicable to nonpolar
      data and unordered multistate characters, and do not have the problems of
      nonindependence that affect split conflict and hierarchy tests. Unlike split
      conflict tests, their power does not appear to be correlated with split size.
      However, all tests are sensitive to taxonomic scope. Split support tests may help
      discern data that are likely to be affected by the problems of long-branches
      effects. Comparison of test results for mutually incompatible splits may help
      identify the presence of strong misleading signals in phylogenetic data.
      Significant split support could be a prerequisite for considering phylogenetic
      hypotheses to be well supported by the data, and split support randomization
      tests might be usefully applied prior to or as part of tree construction.

PMID- 12066311
TI  - Conflicting phylogenetic patterns caused by molecular mechanisms in mitochondrial
      DNA sequences.

PMID- 12066312
TI  - Taxon sampling and the accuracy of large phylogenies.

PMID- 12066313
TI  - Interpreting sister-group tests of key innovation hypotheses.

PMID- 12066314
TI  - Phylogenetic uncertainty, molecular sequences, and the definition of taxon names.

PMID- 12066315
TI  - Combinability of phylogenies and bootstrap confidence envelopes.

PMID- 12066316
TI  - Reverse successive weighting.

PMID- 12066317
TI  - Phylophenetics: frequencies and polymorphic characters in genealogical
      estimation.

PMID- 12066318
TI  - The 'sextasy' craze. Clubland's dangerous party mix: Viagra and ecstasy.

PMID- 12066320
TI  - Meet the gamma girls.

PMID- 12066319
TI  - A 9-11 baby boomlet.

PMID- 12066321
TI  - Selling advice--as well as anxiety.

PMID- 12066322
TI  - Evolution's revolutionary. Stephen Jay Gould, paleontologist: 1941-2002.

PMID- 12066323
TI  - No expert, no lawsuit? No longer.

PMID- 12066324
TI  - Student debt: is one bill better?

PMID- 12066325
TI  - How to talk an elderly patient off the road.

PMID- 12066326
TI  - DNR: did Helen still want to die?

PMID- 12066327
TI  - Don't let dollars walk out the door.

PMID- 12066328
TI  - Get personal in seven minutes? Sure you can.

PMID- 12066329
TI  - If you suspect a partner's impaired.

PMID- 12066330
TI  - An analysis of the retirement and pension plan coverage topical module of SIPP.

PMID- 12066331
TI  - Self-testing of blood glucose: biosensors and beyond.
AB  - There is a possible major shake-up on the way in blood glucose monitoring. Sales
      of disposable electrochemical biosensors now reach approximately US$2.5 billion
      per annum. However, there are numerous rival technologies on the horizon, which
      threaten this leading position. These offer the potential to monitor
      noninvasively or with minimal discomfort. Success in developing any of these has
      the potential to change the future of self-testing of glucose and many other
      analytes.

PMID- 12066332
TI  - Conjugate release materials in lateral-flow assays.
AB  - Conjugate release materials are considered to be the most problematic area in
      lateral-flow strip development. This article describes how these materials can be
      optimised to give a high and consistent degree of conjugate release for a minimum
      of 18 months.

PMID- 12066333
TI  - The technological edge.
AB  - New bench-top instrumentation and novel spin-trapping assays open up the way to
      diagnosing and monitoring a range of conditions associated with rheumatoid
      arthritis and renal disease.

PMID- 12066334
TI  - The IVD directive: planning for compliance.
AB  - In less than 20 months, companies will only be allowed to place in vitro
      diagnostic (IVD) medical devices on the European market if they bear the CE mark.
      For this reason, the process of ensuring compliance with CE-marking requirements
      on or before the end of the transition period, if not already begun, should be
      initiated immediately. This article discusses important compliance issues.

PMID- 12066335
TI  - Standards in the 21st century. Standards past, present and future.

PMID- 12066336
TI  - Clinical investigations and clinical evaluation strategies.
AB  - It is accepted that no device that is clinically effective is entirely without
      hazard, and not all hazards can be known before a device is marketed. This
      article outlines the strategies to adopt when evaluating the benefit-risk ratios
      of high-risk medical devices.

PMID- 12066337
TI  - France: SNITEM demands change to accelerate progress.

PMID- 12066338
TI  - The future of in vitro testing in Europe.

PMID- 12066340
TI  - Achieving quality with machine vision systems.

PMID- 12066339
TI  - Leak testing. Getting down to the fundamentals of leak detection and measurement.
AB  - There are a variety of leak testing techniques in use today. When considering an
      item requiring leak testing it is important to ascertain first whether detection
      of the leak or measurement of the leakage rate is more important. Quantifying the
      leakage rate will dictate the leak measurement technique that is required.

PMID- 12066341
TI  - To test or not to test: the value of biological safety testing.
AB  - Each year, thousands of tests are conducted on biomaterials to check whether they
      are biologically safe and suitable for use in medical devices. This article
      addresses the question of whether or not these tests are necessary, or in fact,
      useful.

PMID- 12066342
TI  - Patient confidentiality: where are we now?

PMID- 12066343
TI  - Epidemiology of meningococcal disease.
AB  - In the UK, serogroup A strains disappeared 50 years ago, but in the 1990s,
      numbers of cases rose again to a 50-year high. Following the very successful
      introduction of conjugated meningitis C vaccines, effective meningitis B vaccines
      are now the highest priority.

PMID- 12066344
TI  - Treating meningococcal infections in children.
AB  - Aggressive early treatment of meningococcal disease in children can reduce
      mortality. This relies on prompt recognition of septicaemia and meningitis, and
      treatment of the complications of shock and raised intracranial pressure.

PMID- 12066345
TI  - Long-term outcomes of childhood meningitis.
AB  - Meningitis and meningococcal disease remain a major source of anxiety to
      paediatricians and parents alike. Survival rates have improved with rapid
      diagnosis and appropriate management. However, survivors remain at risk of long
      term neurodevelopmental sequelae.

PMID- 12066346
TI  - Balance disorders in adults: an overview.
AB  - Dizziness is a common and potentially disabling complaint. A multitude of medical
      and otological conditions may manifest as disequilibrium. Symptomatic improvement
      in peripheral vestibular lesion is the result of central compensation and not
      restoration of normal labyrinthine function.

PMID- 12066347
TI  - The uses and abuses of drains in abdominal surgery.
AB  - Controversy surrounds the indications for and effectiveness of the abdominal
      drain. There are a variety of factors which mitigate against formulating rigid
      guidelines for the indications of drains, but surgeons should understand the
      benefits and applications of drainage and the tissue responses to the constituent
      materials. Drains are not a substitute for meticulous surgical technique.

PMID- 12066348
TI  - Assessment and management of the head-injured patient.
AB  - Head injury is one of the most important causes of serious morbidity and
      mortality in young adults. Each year in Britain, there are approximately 5000
      deaths from serious head injuries. Appropriate multidisciplinary assessment and
      management of systemic and intracranial pathology can significantly improve the
      outcome.

PMID- 12066349
TI  - Advances in the medical management of rheumatoid arthritis.
AB  - New treatments, such as leflunomide and biologic therapy, are making an important
      impact on the management of rheumatoid arthritis. This article reviews the
      efficacy of these agents, the use of combination therapy, and the importance of
      early treatment with a disease-modifying antirheumatic drug.

PMID- 12066350
TI  - Diagnosis and immediate care of open fractures.

PMID- 12066351
TI  - Using an interactive chemotherapy training package to improve patient safety.
AB  - All health-care professionals involved in the use of cytotoxic chemotherapy, if
      they are to avoid serious harm to patients, can benefit from an interactive
      training package in the safe use of these drugs. This article discusses a pilot
      study of a training CD-ROM which was undertaken in a cancer unit.

PMID- 12066352
TI  - Pseudodextrocardia in bronchiectasis.

PMID- 12066353
TI  - Isolated B-cell lymphoma of the pituitary region: a rare clinical entity.

PMID- 12066354
TI  - Necrotizing cutaneous mucormycosis.

PMID- 12066355
TI  - Using the bispectral index for anaesthesia.

PMID- 12066356
TI  - Combined spinal and epidural anaesthesia after a failed epidural.

PMID- 12066357
TI  - Wound competencies & OASIS. One organization's plan.
AB  - Testing assessment competencies in clinical staff can be a challenge, but testing
      wound assessment competency is even more difficult. Add to that the Outcome
      ASsessment Information Set (OASIS) wound questions and it's no wonder that nurses
      are confused. The VNA, Western Pennsylvania decided to take a unique approach to
      wound assessment competencies by combining multiple methods of instruction and
      self-learning followed by a "hands-on" approach to testing.

PMID- 12066358
TI  - Merging roles. A successful approach to wound care in the home.
AB  - Since the Prospective Payment System (PPS) has been in effect for more than one
      year, home health agencies (HHA) are now beginning to feel the true impact of its
      regulations. The PPS environment has motivated HHAs to re-design approaches to
      wound management in order to individualize care, deliver quality, and achieve
      cost-effectiveness. One technique used by HHAs to achieve these outcomes has been
      to merge the roles of Wound Care Specialist (WCS) and Case Manager (CM).

PMID- 12066359
TI  - Pressure ulcers. Nutrition strategies that make a difference.
AB  - One of the more influential factors associated with pressure ulcer prevention,
      development, and treatment is nutrition. Both the Centers for Medicare & Medicaid
      Services (CMS, formerly HCFA) and Agency for Healthcare Research and Quality
      (AHRQ) specifically identify nutritional status as a significant risk factor.
      Three nutrition-focused steps will help you protect patients from the
      debilitating effects of pressure ulcers.

PMID- 12066360
TI  - Maintaining skin integrity.
AB  - One of the most basic needs of patients is to maintain intact, healthy,
      moisturized skin. Intact skin is the body's first line of defense against the
      invasion of microorganisms, provides a protective barrier from numerous
      environmental threats, and facilitates retention of moisture. Unfortunately, many
      routine patient-care activities may have a detrimental effect on the skin and
      consequently, they may develop into significant problems.

PMID- 12066361
TI  - Supplies in demand. Managing medical supplies under PPS.
AB  - It is no longer news that the consolidated billing requirement under the home
      care prospective payment system (PPS) mandates that home care providers are
      responsible for providing specified supplies to patients under a current episode
      of care. With more than one year of experience and data measuring the cost of
      providing supplies, providers are now looking at ways to better manage
      distribution, control utilization, and minimize costs. Although each organization
      must make decisions based on its own needs, several steps in this process have
      proven to be consistently effective.

PMID- 12066362
TI  - Senator Susan Collins: champion of our nation's elderly, disabled, and infirm.

PMID- 12066364
TI  - Healing Medicare.

PMID- 12066363
TI  - BBA 97 hits Louisiana hard.

PMID- 12066365
TI  - Evidence-based health care in home care.
AB  - How do you make decisions about which treatment to use when you have a patient
      with an eschar-covered pressure ulcer on the sacrum or a patient with diabetes
      who develops an ulceration on the metatarsal head? For years, health care
      professionals relied on past experience, the experience of colleagues, or new
      product sales literature. In today's cost-conscious, outcomes-driven health care
      environment, however, approaches such as clinical reasoning are often not enough
      and, in fact, are often unacceptable. But why is that?

PMID- 12066366
TI  - Should we ban the boards?

PMID- 12066367
TI  - Patients who are substance abusers.
AB  - Substance abuse cuts across all social strata. This article offers the dentist
      background information pertaining to drug abuse in the United States, defines
      common terms, discusses the rationale for identifying substance abusers-
      including possible drug interactions--provides a list of "telltale signs" for
      recognizing a chemical abuse problem, and suggests ways to approach a suspected
      abuse problem.

PMID- 12066368
TI  - Preliminary steps in the diagnosis of the pleomorphic adenoma.
AB  - Patients with parotid swellings are often first seen in the dental office. The
      dental practitioner must be able to differentiate a neoplastic lesion from other
      causes of parotid swelling. Knowledge of the modalities that are available to
      distinguish the presence of a tumor and whether the tumor is benign or malignant
      is mandatory. The authors present a case report to illustrate the techniques that
      are used in the preliminary diagnosis of the benign pleomorphic adenoma. Final
      diagnosis awaits the microscopic examination of a surgical specimen.

PMID- 12066369
TI  - Looking for a job? Try dental education.
AB  - The decreasing number of dentists entering a career in academia is considered in
      terms of the evolving changes in the general setting for dental education.

PMID- 12066370
TI  - A message worth repeating.

PMID- 12066371
TI  - HIPAA privacy rule. Slated for modification.

PMID- 12066372
TI  - Responsibility is a two-way street.

PMID- 12066373
TI  - Coding standards remain AHIMA priority in 2002.

PMID- 12066374
TI  - What's your designated record set?

PMID- 12066375
TI  - Communities of practice: harnessing the power of knowledge.

PMID- 12066376
TI  - Connections to care: how technology makes information accessible.
AB  - Healthcare grows safer and more effective all the time, due in part to Internet
      based technology. In this article, learn how healthcare facilities are using the
      electronic medical record, telemedicine, personal digital assistants, and more to
      transform healthcare delivery.

PMID- 12066377
TI  - Your job in the e-health era.

PMID- 12066378
TI  - Uniting security forces against risk.
AB  - Threats to your facility's physical and information security become more complex
      all the time. To create a truly effective security program, consider developing
      an integrated security program that encompasses both traditional and information
      technology protection. The result? A strong, streamlined program that enables-
      not inhibits--healthcare delivery.

PMID- 12066379
TI  - The pursuit of excellence in medical record reviews.
AB  - The ongoing medical record review program at Sioux Valley Hospital USD Medical
      Center needed reenergizing: the results weren't taken seriously or producing the
      needed improvements. Using tools from the Joint Commission, an HIM professional
      and a performance improvement coordinator redesigned the process, making it more
      efficient and more effective. Here's how they did it.

PMID- 12066380
TI  - Closing the knowledge gap with e-learning.
AB  - Are high costs and potential downtime preventing your staff from receiving much
      needed training? E-learning offers more than a solution to these concerns: it's a
      better way to learn. In this article, find out how e-learning works and how to
      implement an e-learning program in your organization.

PMID- 12066381
TI  - Practice brief. Recommended regulation and standard acquisitions for specific
      healthcare settings (updated).

PMID- 12066382
TI  - Spreading HIM excellence abroad.

PMID- 12066383
TI  - Privacy and security: are two hats better than one?

PMID- 12066384
TI  - Keeping HIM current through re-engineering.

PMID- 12066385
TI  - Society for Clinical Coding comes around as CoP (Communities of Practice).

PMID- 12066386
TI  - A closer look: the SNOMED clinical terms to ICD-9-CM mapping.

PMID- 12066387
TI  - Facilitator no stranger to cyberspace. Interview by Anne Zender.

PMID- 12066388
TI  - Managed care gets a closer look from feds. Investigation pinpoints HMOs, free
      drug samples from pharmaceutical firms and Medicare fraud.

PMID- 12066389
TI  - Mayo Clinic closes last HMO.

PMID- 12066390
TI  - When an agreement is not one.

PMID- 12066391
TI  - State secrets. Congress plans hearings on Medicaid waivers.

PMID- 12066392
TI  - Wis. hospitals fight proposals. Lawmakers push more restrictions on construction.

PMID- 12066393
TI  - One problem we can't staff out. Healthcare worker shortage won't go away until
      the industry takes action.

PMID- 12066394
TI  - Going to waste. One surgeon's trash can be a hospital's treasure as providers
      figure out how to minimize opening supplies that don't get used.

PMID- 12066395
TI  - Anything but idle. While some providers, stuck in neutral, wait for final HIPAA
      rules, Saint Luke's health system hits high gear preparing.

PMID- 12066396
TI  - Straight talk: new approaches in healthcare. Integrated revenue cycle operations-
      leveraging technology and human capital.
AB  - This is the third installment in a series of group discussions by top executives
      on key issues in healthcare today. Straight Talk is presented by Modern
      Healthcare and PricewaterhouseCoopers. This session tackles the subject of
      revenue-cycle management. Moderated by Charles S. Lauer, the discussion was held
      on May 7, 2002 at Modern Healthcare's Chicago headquarters.

PMID- 12066397
TI  - Healthcare's crown jewels. A looming 15% reduction in Medicare payments could
      tarnish the financial viability of teaching hospitals, studies say. Others,
      however, say they'll keep shining despite the scheduled cuts.
AB  - Though saddled with higher costs than other hospitals, teaching hospitals reap
      plump margins on Medicare. But that could change this fall. A volley of studies
      say a looming 15% cut in indirect medical education payments and disproportionate
      share payments could threaten the financial viability of healthcare's crown
      jewels unless Congress reverses current law.

PMID- 12066398
TI  - Tales from the marketing front.

PMID- 12066399
TI  - Strong relationships start with education.

PMID- 12066400
TI  - Did you hear? Consumers tune in to multimedia marketing.

PMID- 12066401
TI  - Taking U.S. health services overseas.

PMID- 12066402
TI  - Smart thinking for challenged health systems.

PMID- 12066403
TI  - Patient loyalty that lasts a lifetime.

PMID- 12066404
TI  - Building on first impressions. These days, attractive facilities are their own
      marketing tool. Interview by Richard K. Thomas.

PMID- 12066406
TI  - Seven steps to E-health success.

PMID- 12066405
TI  - A hospital Web site that works.

PMID- 12066407
TI  - Cellular components of neuroinflammation--an introduction.

PMID- 12066408
TI  - Activated microglia in Alzheimer's disease and stroke.

PMID- 12066409
TI  - Microglia and the response to brain injury.

PMID- 12066410
TI  - Inflammation in stroke--a potential target for neuroprotection?

PMID- 12066411
TI  - Neuroinflammation in Alzheimer's disease: potential targets for disease-modifying
      drugs.

PMID- 12066412
TI  - The concept of in vivo imaging of neuroinflammation with [11C](R)-PK11195 PET.

PMID- 12066414
TI  - The role of apoptosis in neuroinflammation.

PMID- 12066413
TI  - Chemokine receptors on mononuclear phagocytes in the central nervous system of
      patients with multiple sclerosis.

PMID- 12066415
TI  - Elucidating molecular mechanisms of Alzheimer's disease in microglial cultures.

PMID- 12066416
TI  - Neuronal SLC (CCL21) expression: implications for the neuron-microglial signaling
      system.

PMID- 12066417
TI  - Cytokine-mediated inflammation and other actions in the central nervous system.

PMID- 12066418
TI  - BSE, scrapie, and vCJD: infectious neurodegenerative diseases.

PMID- 12066419
TI  - When are morphemic and semantic priming observed in visual word recognition?
AB  - J. Stolz and D. Besner (1998) reported a dissociation between morphemic and
      semantic priming in the context of lexical decision. Morphemic priming was
      observed following letter search on the prime display, but semantic priming was
      not. Participants in the present experiment identified the colour of a single
      letter in the prime display before making a lexical decision to the target. Both
      morphemic and semantic priming were observed. These results are discussed in
      relation to the observation that identifying the colour of a single letter of a
      word in the Stroop task is associated with a reduction in the size of the Stroop
      effect as compared to when all letters are coloured.

PMID- 12066420
TI  - Short-term memory and time estimation: beyond the 2-second "critical" value.
AB  - We showed previously that when time intervals around two seconds (s) are
      reproduced concurrently with a memory task, intervals are positively related to
      duration of memory processing. However, some data in research on timing as well
      as in memory research suggest that 2 s might be a critical duration beyond which
      different mechanisms or structures would support performance. This implies that
      the interference observed between memory processing and 2-s productions could be
      specific to these durations, and would not be obtained with longer durations. In
      this experiment, intervals ranging from 1.85 to 6.45 s were reproduced by
      participants, who were searching simultaneously for a memory probe. At all
      durations, reproductions were positively related to memory set size. These
      findings have implications with regards to previous research indicating a
      discontinuity around 2-3 s in time perception. They suggest in particular that
      the role of memory is similar in reproduction of durations around 2 s and of
      longer durations.

PMID- 12066421
TI  - Sample size, confidence, and contingency judgement.
AB  - According to statistical models, the acquisition function of contingency
      judgement is due to confidence increasing with sample size. According to
      associative models, the function reflects the accumulation of associative
      strength on which the judgement is based. Which view is right? Thirty university
      students assessed the relation between a fictitious medication and a symptom of
      skin discoloration in conditions that varied sample size (4, 6, 8 or 40 trials)
      and contingency (delta P = .20, .40, .60 or .80). Confidence was also collected.
      Contingency judgement was lower for smaller samples, while confidence level
      correlated inversely with sample size. This dissociation between contingency
      judgement and confidence contradicts the statistical perspective.

PMID- 12066422
TI  - Blinded by headlights.
AB  - Target identification is impaired when targets are presented during the planning
      or execution of a compatible response (e.g., right-pointing arrow during a right
      keypress) relative to an incompatible response (Musseler & Hommel, 1997 a, b).
      Examinations of this blindness to response-compatible stimuli have typically used
      arrowheads as targets ("<" and ">"). The importance of the target symbol was
      examined by manipulating subjects' interpretation of that symbol (i.e., ">"
      interpreted as a right-pointing arrow or as a headlight shining to the left).
      Targets were presented at varying times during the planning or execution of a
      response in order to examine the time-course of the effect. Results showed that
      the interpretation, and not the physical identity, of the target was important
      for the blindness effect. Although the blindness effect was largest during the
      planning and execution of a response, it was not always confined to that temporal
      interval.

PMID- 12066423
TI  - [Treatment dynamics in sensorimotor disorders: the contribution of
      electrophysiology].
AB  - In the field of sensorimotor activities, progresses achieved over the last fifty
      years have been largely driven by the Reaction Time (RT) paradigm. Information
      processing models are set in the context of a global breakdown of sensorimotor
      activities in multiple concatenated stages, each aggregated in many fundamental
      operations that are functionally linked. If there is a consensus today about this
      breakdown, the way stages organize themselves in time however is still much
      debated. According to one hypothesis, there is no temporal overlap between each
      stages: the process occurs sequentially. According to another theory, the stages
      overlap over in time: the process occurs in a parallel manner. A behavioral
      analysis does not allow to determine between these two hypothesis because the RT
      represents the final product of the whole sensorimotor pathway, while the
      temporal organization of the processing of information depends on the nature of
      the transfer between individual stages. An all-or-nothing information transfer,
      also called discrete, leads to a sequential organization, while a progressive or
      continuous transfer brings about a parallel organization. Moreover, contrary to a
      preconceived notion, data obtained from classical neurophysiology are compatible
      with both a sequential organization and a parallel organization. Particularly,
      the great number of connections between the different elements of the nervous
      system has often seemed difficult to conciliate with a sequential organization.
      In fact, this argument is inadmissible because it stems from confusion between a
      temporal organization and an anatomical organization of the processing of
      information. More generally, our knowledge of the functional anatomy of
      sensorimotor activities imposes but few constraints on the temporal organization
      patterns of the processing of information. The lack of interest for the
      neurophysiological argument seems essentially due to the fact that theses
      arguments rest on research which is not aimed at the temporal organization of the
      sensorimotor information processing. Recently, approaches that integrate concepts
      and methods used in experimental psychology and neurosciences have contributed to
      putting in perspective the organization of information processing.
      Electromyography, EEG, reflexology and neuronal recording techniques have been
      used in the context of two inference logics. The first logic, that we call
      "factual", is based on the study of functional relations between RT and certain
      neuronal events. The second logic, that we call "chronometric", is based on the
      study of the relationships between RT and intervals resulting from the breakdown
      of the RT in relation to certain neuronal events. Generally speaking, most
      studies suggest that in tasks where the stimulus is composed of numerous
      attributes, information processing operates in parallel. On the other hand, when
      the stimulus is made up of a single attribute, information processing could be
      operating in a sequential manner. One weakness of this electrophysiological
      approach is that it has so far only examined relationships between physiological
      indicators and means RT. We propose here to offset these weaknesses by examining
      functional relationships between RT distribution variances and certain neuronal
      events linked to information processing.

PMID- 12066424
TI  - Repetition deficits, list context, and word-class interactions in the RSVP of
      words in sentences.
AB  - We report a failure to find a repetition deficit in recall following the rapid
      serial visual presentation (RSVP) of words within sentences, using adjectives
      rather than nouns as the critical items. In a series of experiments that ruled
      out participant and procedural differences as the source of the failure, both
      word class and list context were found to moderate the repetition deficit, but
      grammatical necessity did not. The presence in the list of sentences in which the
      repeated adjectives were separated by more than three words (i.e., more than 400
      ms in RSVP) not only eliminated the repetition deficit for the recall of those
      sentences but also for the recall of sentences in which the repeated adjectives
      were separated by three or fewer words (i.e., less than 400 ms in RSVP). However,
      although substantially reduced, a repetition deficit with noun-based materials
      was still found in this list context. Matching the adjective-based sentences with
      the noun-based sentences in sentence length and position of the critical items
      revealed that the moderating effect of word-class on the repetition deficit was
      mediated by the biases in sentence structure that using different word classes
      tend to induce.

PMID- 12066425
TI  - [Prevalence of and risk factors for hepatitis C in blood donors].
AB  - OBJECTIVE: Determine hepatitis C prevalence and risk factors in blood donors from
      the Blood Bank at the Centro Medico Nacional 20 de Noviembre ISSSTE, in Mexico
      City. METHODS: A total of 41,957 blood donors were included in the study was done
      from January 1996 to August 2000. To study risk factors, a case-control study
      cases were defined as blood donors with repeatedly positive anti-hepatitis C
      virus (HCV) ELISA test. Controls were defined as blood donors with negative anti
      HCV ELISA test. All cases were interviewed a second time on HCV infection
      associated risk factors. Odd ratio (OR) and confidence interval 95% (CI 95%) were
      calculated for each risk factoring in a univariate analysis. Multivariate
      analysis was performed subsequents to determine the independent contribution or
      each risk factor. RESULTS: HCV crude total prevalence was 0.84%. Risk factors
      were found in 36.16% anti-HCV-positive blood donors. During the second interview,
      30% of sero-positive blood donors recalled one or more risk factors they
      previously denied. The most important risk factors, found were as follows sexual
      relations with prostitutes (OR 7.48, CI 95% 1.43-38.92) transfusion (OR 6, CI 95%
      2.62-13.72); nasal cocaine use (OR 8.89, CI 95%, 1.01-86.89); dental surgery (OR
      8.89, CI 95% 1.01-86.89) and contact with hepatitis-infected subject (OR 3.01, CI
      95% 1.17-7.70). Other risk factors did not show a significant association.
      DISCUSSION: In this study, we found a crude total prevalence of 0.84%, very close
      to the prevalence reported in Mexican population by the National Center for Blood
      Transfusion.

PMID- 12066426
TI  - [Primary gastric lymphoma. Clinico-pathologic features of a Mexican series].
AB  - OBJECTIVE: To analyze pathologic and clinical features in patients with primary
      gastric lymphoma (PGL) in a reference hospital in Mexico City, and to evaluate
      the variety of treatments chosen. METHODS: Patients with primary gastric lymphoma
      between 1975 and 2000. Those with histological diagnosis of primary gastric
      lymphoma confirmed by endoscopic biopsy or gastrectomies were eligible for
      inclusion in the study. The study was retrolective. RESULTS: Forty-two patients
      (21 M, and 21 F) with an average age of 57 years (between 20 and 80 years). The
      major clinical findings were no weight loss in 31 patients (73%), abdominal pain
      in 24 patients (57%), gastrointestinal pair in 19 patients (45%), and early
      satiety in 15 patients (36%). The endoscopic findings were gastric folds in 21
      (50%), thickening of gastrics folds in 13 (31%) and tumor in eight patients
      (19%). We found H pylori in 14 of 16 endoscopic biopsies (87%). High grade
      lymphomas were found in 29 patients (69%) and low grade lymphoma in 13 (31%). The
      clinical stage according to the Staging Classification from the Fifth
      International Conference on Malignant Lymphoma (1993) was 15 patients in stage I
      (36%), 14 patients in stage II1 (33%). Five patients in stage IV (12%), six
      patients in stage IIE (14) and one patient in stages II and II2 (2%). The
      treatment chosen before 1990 was surgery with or without chemotherapy no matter
      the grade of malignancy, in contrast with the later decade in which solely
      eradication of H pylori was successfully to cure the disease. In high grade
      lymphomas, treatment was surgery and chemotherapy for reviewing the study, most
      patients were alive and without disease. CONCLUSIONS: In the study, most
      lymphomas were localized in the stomach of perigastric lymph nodes. The most
      frequent clinical stages were stages I and II1 (36 and 33%, respectively), and
      their response was successful to all treatments even though most patients were
      high graded and treated differently.

PMID- 12066427
TI  - [Helicobacter pylori gastric infection is a protection factor for
      gastroesophageal reflux disease].
AB  - OBJECTIVE: To know the relationship between endoscopic esophagitis and H. pylori
      infection. BACKGROUND: The incidence of gastric cancer and peptic ulcer disease
      has declined in recent years, while GERD, Barrett esophagus, and distal
      esophageal adenocarcinoma have increased. Some authors think these epidemiologic
      changes are related to the simultaneous decrease in H. pylori colonization.
      METHOD: From 1997 to 1999, 192 patients underwent gastrointestinal endoscopy and
      detection of H. pylori (rapid urease test and/or seric antibodies and/or
      histologic examination and/or C13 marked urea). Patients were retrospectively
      divided according to endoscopic diagnosis of esophagitis (Savary-Miller) and
      positivity of any H. pylori test. Both groups were compared using Fisher exact
      test and odds ratio (OR) with 95% confidence intervals (CI 95%). RESULTS: A total
      of 80 (40.6%) were H. pylori-positive without esophagitis, and 18 (9.4%) had
      esophagitis and H. pylori positivity (p = 0.01) [OR = 0.39 (CI 95% = 0.15-0.62)].
      Of the remaining 133 patients, after separating those who received treatment that
      could modify GERD (n = 59), and 50 (37.6%), were H. pylori without positive
      without esophagitis) 18 (13.5%) had esophagitis and H. pylori positivity
      maintaining significance p = 0.003) [OR 0.32 (CI 95% (-0.1)-0.8)]. The severity
      of the esophagitis (Savary-Miller) was compared with the presence of Helicobacter
      pylori, but no relationship was found (p = 0.3). CONCLUSIONS: 1) Helicobacter
      pylori infection seems to be a protective factor for the presence of endoscopic
      esophagitis. 2) When esophagitis is present, the degree of damage appears to be
      independent of the H. pylori infection.

PMID- 12066428
TI  - [Colonic primary lymphoma].
AB  - Primary colon lymphomas (PCL) are very rare tumors of the gastrointestinal tract,
      and represent 0.2-0.5% of all colon primary tumors. They appear principally PCL
      in adult population. Almost all are non-Hodgkin's lymphomas; first however, one
      must discard lymph node origin. The most frequent sites of presentation are the
      cecum and rectum. Treatment of choice is surgical, plus adjuvant chemotherapy.
      Radiotherapy is reserved for specific cases. OBJECTIVE: To inform on two cases of
      PCL. METHOD: Review two of cases of cecum lymphomas and their treatment. RESULTS:
      We inform the cases of two patients with the diagnosis of cecum lymphoma. The
      main patient complaints were abdominal pain, palpable mass, and hemorrhage. Both
      patients were treated with right extended hemicolectomy and ileum-transverse
      anastomosis. The outcome was unremarkable. Both patients received chemotherapy
      and remain free of disease at 1.5 and 5 years of follow-up. CONCLUSIONS: Primary
      colon lymphomas are very uncommon gastrointestinal tumors, with cecum
      localization as one of the most frequent sites of presentation in the colon.
      Treatment of choice must be surgical, with chemotherapy as an adjuvant therapy to
      improve survival.

PMID- 12066429
TI  - [Intestinal obstruction secondary to biliary ileus].
AB  - OBJECTIVE: To discuss diagnostic and therapeutic implications of gallstone ileus
      and to report the case of a patient seen at our Hospital due to an intestinal
      obstruction secondary to gallstone ileus. REPORT: A 63 years old male with
      intestinal obstruction secondary to gallstone ileus. Several studies were
      performed, such as panendoscopy, upper gastrointestinal series, and intestinal
      transit with poor results preventing a definitive diagnosis. For this reason, the
      patient underwent an exploratory laparotomy, which showed in this a grant
      gallstone in a giant jejunum. TREATMENT: Enterotomy, gallstone extraction, and
      enteroraphy. COMMENT: The intestinal obstruction secondary to gallstone ileus is
      a clinical entity of difficult diagnosis. Accompanying studies usually have low
      sensibility because other pathologic entities are considered prior to thinking of
      ileus gallstone.

PMID- 12066430
TI  - [Superior mesenteric artery syndrome as a cause of chronic partial intolerance to
      oral feeding. Report of a case and review of the subject].
AB  - INTRODUCTION: Superior mesenteric artery syndrome (SMAS) is the obstruction of
      the duodenum in the third portion due to this artery. We present a case of
      chronic oral feeding intolerance due to this problem. CLINICAL CASE: A 24 year
      old woman, with a time of evolution of 1 year and a half of postprandial
      epigastric pain with nausea, vomiting, and loss of 30 kg managed as acid-peptic
      disease. The patient was studied with gastrointestinal contrast study and
      endoscopy without conclusive results. The patient was admitted for unstoppable
      vomiting, malnutrition, and severe dehydration. A laparotomy was performed and
      SMAS was identified. We performed Treitz's ligament section and
      gastrojejunoanastomosis. Her clinical outcome was satisfactory and the patient
      was discharged without complications. DISCUSSION: SMAS is also called Wilkie's
      syndrome. SMAS is more frequent in women between the 10 and 39 years. The disease
      due to the decrease of the angle between the superior mesenteric artery and the
      aorta, to the anomalous origin of this artery, or to the shortening of Treitz's
      ligament. SMAS may appear as a sudden weight loss. Food intolerance is a
      predominant symptom. Diagnosis can be made with x-ray studies. Treatment is
      medical or surgical, with Treitz's ligament section, duodenojejunoanastomosis,
      and in some cases gastrojejunoanastomosis. CONCLUSIONS: SMAS should be considered
      as no the differential diagnosis of chronic oral feeding intolerance.

PMID- 12066431
TI  - [Primary non-Hodgkin's lymphoma of the liver. Report of a case and review of the
      literature].
AB  - Primary hepatic lymphoma (PHL) is a rare tumor and its clinical behavior remains
      unknown. We report a case of PHL in a 47 year-old male patient without chronic
      liver disease and with preoperative diagnosis of hepatocellular carcinoma.
      Hepatitis B surface antigen and antibody and anti-hepatitis C virus antibody were
      negative. The patient underwent a right trisegmentectomy, and pathologic
      examination revealed a diffuse large B-cell lymphoma. The clinical and pathologic
      features are presented. A review of the literature discussing clinical features,
      postulated pathogenetic mechanisms, and management options are also presented.

PMID- 12066432
TI  - [Microscopic colitis].
AB  - BACKGROUND: Microscopic colitis is responsible for a proportion of difficult
      diagnosis cases with chronic diarrhea. Diagnosis is clinically suspected when
      chemical and macroscopic examination result negative and is made only by
      histopathologic findings. OBJECTIVE: To describe clinical, biochemical,
      colonoscopic, and histologic features and the treatment response of four cases
      with microscopic colitis. METHODS: We inform on the findings in four females
      patients presenting with chronic watery diarrhea with normal biochemical and
      colonoscopic tests. RESULTS: In these cases, diagnoses mode were lymphocytic
      colitis two and collagenous colitis two. The long term duration of watery
      diarrhea was 5 months. The average number of depositions were 10 in 24 h.
      Diagnosis was made after microscopic examination of the colonic mucosa in the
      absence of endoscopic abnormalities and normal chemistries. All patients had a
      satisfactory response to treatment. CONCLUSIONS: The diagnosis of microscopic
      colitis is made by histopathology findings. The therapeutic response is generally
      satisfactory.

PMID- 12066433
TI  - [Percutaneous endoscopic gastrostomy. Is it safe to start eating immediately?].
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is a simple procedure with
      few associated complications. Traditionally, diet can be initiated 24 after the
      placement of the probe, but there is no information concerning safety with
      immediate feeding. OBJECTIVE: To compare safety of immediate feeding against late
      feeding after placement of PEG. MATERIALS AND METHODS: A total of 62 patients
      referred for placement of a PEG were assigned alternatively to start feeding
      during the first 30 min after the procedure was finished (group A), or 24 h later
      (group B). All patients received the same formula and remained hospitalized for
      three days. During follow-up, data for local infection and mild or severe
      complications were intentionally sought. RESULTS: Each group was composed of 31
      patients; both groups were similar in age, gender, indication for placement of
      PEG, presence of infections, and use of antibiotics. Two patients of group A and
      six of group B developed local infections (six vs. 19%, p = NS value). Mild
      complications were found in three patients of group A and two A of group B (10
      vs. 6%, p = NS). Severe complications were found in one patient of group A and
      two of group B (3 vs. 6%, p = NS). CONCLUSIONS: Immediate feeding after placement
      of a PEG is a safe practice.

PMID- 12066434
TI  - The dentist-laboratory relationship: a system for success.
AB  - There are many changes occurring in the field of dentistry that are impacting the
      way dental offices and dental laboratories must work with each other. Materials
      and procedures are changing at an extremely rapid pace. At the same time, the
      knowledge and demands of the patient continue to rise. In order to navigate
      through these challenging waters, the relationship between dental office and
      laboratory must become one of corroboration and partnership. The relationship
      between dentists and laboratories should be viewed as an interactive system. With
      full participation, better education, and wise management of information, this
      partnership can grow to the benefit of all concerned.

PMID- 12066435
TI  - There is no standing still.
AB  - Changes in dentistry are leading to new and more interdependent relationships
      among dentists, patients, and laboratories. Most important among these emerging
      forces are the rapid development of new product technologies, dentists' desire to
      increase their financial and creative satisfaction, and changing demographics and
      customer involvement.

PMID- 12066436
TI  - Future of dentistry--education chapter. Recommendations for dental education.

PMID- 12066437
TI  - Picking your patients.

PMID- 12066438
TI  - Bridge to dentistry: one dental school's approach to improving its enrollment of
      underrepresented minorities.
AB  - Presently, 25.7% of the U.S. population is comprised of Blacks/African Americans,
      Hispanics, and Native Americans. The dental school enrollment of underrepresented
      minorities (URM) does not reflect this demographic distribution. In 1994, URM
      students comprised 12.68% of enrolled dental students, but in 1999, enrollment
      decreased to 10.53%. This trend is evident at Baylor College of Dentistry (BCD).
      Bridge to Dentistry involves formal linkages with local school districts, Texas
      colleges and universities, community organizations, dental clinics, community
      dentists, and BCD. The program is unique in that it targets students from
      kindergarten through dental school. The key components are awareness, attraction,
      preliminary education, facilitated-entry, admissions, financial aid, and
      retention. Some important features of the program are visits to area schools,
      visits to colleges and universities, summer enrichment programs, and academic
      advising. Preliminary results indicate the effectiveness of the program. BCD has
      increased its enrollment of URM students 325% over that of 1998. In 1998, 4.7% of
      the college's first-year student enrollment was URMs. In 2001, 14.6% of Baylor's
      first-year student enrollment was URMs. Since 1995, BCD has retained 90.6% of its
      URM students.

PMID- 12066439
TI  - Use of an inventory for ethical awareness in dental hygiene.
AB  - This is a study of practicing dental hygienists and dental hygiene students
      undertaken to ascertain their perceived awareness of ethical, moral, and legal
      matters and their convictions about being knowledgeable in dealing with them. The
      study focused on identifying ethical concerns that dental hygienists maintain as
      being professionally significant and the differences, if any, between currently
      enrolled students and dental hygiene practitioners.

PMID- 12066440
TI  - Ethical dentistry: a time proven solution to a modern problem.

PMID- 12066441
TI  - Why.
AB  - There are two kinds of cause and effect. The scientific notion that is taught as
      part of the formal model is rigorous, but often limited in its generalizability
      across situations. The study of cause and effect in natural settings is also a
      rigorous field, with several useful and easily applied techniques. Root cause
      analysis is a set of approaches to identifying the factors in natural settings
      that initiate a chain of events with outcomes of interest. It is easier to
      improve processes when their true root causes have been identified. Risk
      management is a special case of root cause analysis.

PMID- 12066442
TI  - The changing roles of the dentist and dental laboratory.
AB  - There are growing pressures on the relationship between the profession and
      laboratories, including increased use of sophisticated prosthetic services, rapid
      evolution of materials, more "educated" patients, declining numbers of laboratory
      training programs and relatively reduced hours in dental schools in traditional
      prosthodontics subjects, and consolidation in the dental laboratory industry.
      Restorative services represent the greatest cost/value center in most practices,
      and the ADA's "Future of Dentistry Report" calls for the profession reasserting
      its "control" in this area. It is proposed instead that a partnership among the
      profession, laboratories, manufacturers, and education represents the most
      effective way to guide the emerging future of restorative dentistry for the
      benefit of patients and the concerned parties.

PMID- 12066443
TI  - The dental laboratory dilemma in America.
AB  - Dentistry has lost some of its "touch" with the technical, laboratory aspects of
      the profession. More cooperation is needed between dentists and laboratory
      technicians in their education, in practice, and at the organizational level.

PMID- 12066444
TI  - JPN and the electronic revolution.

PMID- 12066445
TI  - Neuroactive steroids and anxiety disorders.

PMID- 12066446
TI  - What's in a name? The evolution of the nomenclature of antipsychotic drugs.
AB  - OBJECTIVE: Psychiatry as a science and psychotherapy as an art thrive on words,
      words that were often coined arbitrarily and that are often used
      idiosyncratically. This article examines the origins, progenitors and usage of
      the word "antipsychotic" and explores its ramifications. METHODS: Original
      publications from the 1950s onward, beginning with the report of the discovery of
      chlorpromazine, were sought for their specific references to the terminology of
      drugs used to treat psychotic disorders. Preferences for individual words,
      debates surrounding their adoption and changing trends in their use are reviewed
      from scientific, clinical and social perspectives. RESULTS: Over the past 50
      years the drugs used in the treatment of schizophrenia and other psychotic
      disorders have been variously labelled "tranquillizers," "neuroleptics,"
      "ataractics," "antipsychotics" and "anti-schizophrenic agents." These terms,
      coined out of necessity, were quickly accepted with little debate or due
      consideration of their clinical, personal and social implications. The
      development of a new generation of antipsychotic drugs as well as the prospect of
      treatment strategies with diverse mechanisms of action highlight the need to re
      examine the issues involved in the naming, classification and labelling of
      psychotropic drugs in general and of "antipsychotics" in particular. CONCLUSION:
      This historical overview of the labelling of drugs used in the treatment of
      psychoses reflects the confusion and controversy surrounding the naming and
      classification of drugs and diseases in general. It also illustrates the dynamic
      interplay of personal beliefs, rational thinking, practical considerations and
      societal values in shaping the scientific process.

PMID- 12066450
TI  - Playing God with the Big Muddy. Should man-made dams let the Missouri River flow
      wild again?

PMID- 12066448
TI  - Cognitive functioning in first-episode schizophrenia.
AB  - OBJECTIVE: To compare the cognitive functioning of a sample of patients
      experiencing their first episode of schizophrenia with that of patients with an
      established schizophrenia illness. DESIGN: Cross-sectional and longitudinal
      study. SETTING: The Calgary Early Psychosis Treatment and Prevention Program and
      an outpatient clinic in a department of psychiatry at a university-affiliated
      hospital. PARTICIPANTS: One hundred and eleven patients who were experiencing
      their first episode of schizophrenia and 76 outpatients with an established
      schizophrenia illness. MEASURES: The Positive and Negative Syndrome Scale for
      schizophrenia was administered to all subjects to determine levels of positive
      and negative symptoms. Executive functioning, information processing, visual
      memory, and immediate and delayed verbal memory were assessed. RESULTS: There
      were limited differences between the 2 groups in terms of cognitive functioning.
      Although the first-episode patients demonstrated generally superior scores, their
      performance was impaired. CONCLUSIONS: These results support the findings of
      previous studies suggesting that first-episode patients demonstrate cognitive
      impairments similar to those of patients with an established schizophrenia
      illness.

PMID- 12066449
TI  - Olanzapine-induced mania in bipolar disorders.

PMID- 12066447
TI  - Clonidine potentiates the effects of tranylcypromine, phenelzine and two
      analogues in the forced swimming test in mice.
AB  - OBJECTIVE: To compare tranylcypromine (TCP) and phenelzine (PLZ), two well
      established inhibitors of monoamine oxidase (MAO), and 2 of their analogues, 4
      fluorotranylcypromine (FTCP) and N2-acetylphenelzine (AcPLZ) respectively, with
      regard to effects in the forced swimming test, a behavioural test used to screen
      for potential antidepressant drugs. METHODS: Mice were dropped individually into
      glass cylinders containing water. The duration of their immobility was scored
      during the last 4 minutes of the test. RESULTS: Except for TCP at high doses,
      none of the drugs demonstrated activity when administered alone. All 4 drugs were
      active when given in combination with clonidine, an effect thought to be the
      result of mixed action at 5-HT1A and 5-HT2 receptors and the noradrenergic
      system. 5-HT18 receptors do not seem to be implicated, as lithium did not
      potentiate the effect of any of the drugs. Quinine activation of AcPLZ suggests
      that this analogue acts on 5-HT3 receptors. CONCLUSIONS: FTCP and AcPLZ
      demonstrated anti-immobility activity in the forced swimming test when used in
      association clonidine. These findings confirm previous neurochemical findings
      suggesting that these drugs have antidepressant properties.

PMID- 12066451
TI  - More cover-ups, more shame.

PMID- 12066452
TI  - Phys ed redux.

PMID- 12066453
TI  - A hungry hormone.

PMID- 12066454
TI  - Cancer medicine hits a target.

PMID- 12066455
TI  - Breast cancer face-off.

PMID- 12066456
TI  - Consuming passion. The mentally ill are taking charge of their own recovery. But
      they disagree on what that means.

PMID- 12066457
TI  - High-wire health.

PMID- 12066458
TI  - All in the family. Putting every creature with its kin on the tree of life.

PMID- 12066459
TI  - Engineered to run wild. Genetically altered animals could be released to fight
      pests and disease.

PMID- 12066460
TI  - Retirement realities. Planning and purpose can lead to a whole new life.

PMID- 12066461
TI  - Retirees' social insecurity. When to start taking Social Security benefits
      becomes a tricky issue for many.

PMID- 12066462
TI  - A prescription for poverty. Rising drug prices pinch many retirees who must foot
      their own Rx bills.

PMID- 12066463
TI  - Staving off the many aches of age.

PMID- 12066464
TI  - 100 and counting.

PMID- 12066465
TI  - Lean and hungrier.

PMID- 12066466
TI  - Beyond premenstrual syndrome.

PMID- 12066467
TI  - [Retrograde locking nail osteosynthesis with the dynamic femoral nail].

PMID- 12066468
TI  - [Retrograde locking nail osteosynthesis of distal femoral fractures with the
      distal femoral nail (DFN)].
AB  - Non-operative treatment with immobilization or isometric traction has been
      abandoned as treatment for fractures of the distal femur at the end of the
      1960ies. The technique of open reduction and internal fixation with a condylar
      plate as suggested by the AO has been the golden standard since the 1970ies.
      However, anatomic reconstruction of the condylar region with interfragmentary
      screw fixation and axial realignment of the femur shaft with a plate are
      challenging procedures especially in the presence of severely compromised soft
      tissues and put periosteal blood supply at risk. Soft tissue complications, axial
      malalignment and delayed fracture healing times led to the consideration of
      alternative techniques, such as intramedullary nailing which has been practiced
      with success since the 1940ies by Gerhard Kuntscher and colleagues for femoral
      shaft fractures with minimal complication rates and improved results after closed
      reduction. The era of retrograde femoral nailing began with the systematic
      approach through the intercondylar notch by Green. This paper reviews the
      biomechanical properties, indication, technique as well as potential hazards and
      pitfalls of fracture management with the AO "distal femoral nail" (DFN). With
      appropriate application this technique is suitable for all fractures of the
      distal third of the femoral shaft including highly instable bicondylar fractures
      without damage to the soft tissues and the knee joint.

PMID- 12066469
TI  - [Primary external fixation with consecutive procedural modification in
      polytrauma].
AB  - AIM OF STUDY: It is the purpose of the current investigation to determine whether
      immediate external fixation of fractures, which is a simple and fast procedure,
      followed by secondary planned conversion represents a safe and reliable procedure
      without additional trauma in multiply injured patients (ISS > 15). METHODS: With
      a prospective protocol, all data of multiply injured patients with fractures
      which required immediate osteosynthesis were registrated. Demographic data,
      severity of injury (AIS and ISS), data of primary surgery and osteosyntheses,
      course of intensive care (organ failure, local/systemic complications, infectious
      protocol), secondary conversion (time, duration, osteosynthesis related
      complications) and further course were analysed. RESULTS: Out of 679 mulitiply
      injured patients (ISS 22), 118 required immediate surgical procedures for
      intracranial injury and 175 for further indications. In 45 multiply injured
      patients (ISS 37), 83 external fixations were performed. According to 59 planned
      secondary conversions (13 days), one patient developed deep infection, no other
      local complication was registrated. The average time for conversion procedures
      lasted three times longer as in immediate external fixation (43 vs. 139 min).
      CONCLUSIONS: Immediate external fixation in multiply injured patients is fast and
      poor of complications. It is a expedient procedure which is safe and careful for
      critically ill patients. The required conversion procedure shows no raised rate
      of complications.

PMID- 12066470
TI  - [Pterional orbital decompression in traumatic orbital hematomas].
AB  - The results are presented for pterional orbital decompression in 12 patients with
      symptomatic traumatic retrobulbar hematoma after various traumatic mechanisms.
      Pre- and postoperative course, neuroradiological findings, additional brain or
      facial injuries as well as outcome of eye function are analyzed in detail. Mean
      time delay between trauma and decompression was 56 h (2.4 days), with a wide
      range from 2 h to 15 days. Preoperative exophthalmos and pupillary disturbances
      as well as restrictions of extraocular movements decreased in all patients after
      orbital decompression and removal of the retrobulbar hematoma if the bleeding was
      localized. Visual acuity remained normal or showed significant improvement in
      seven patients, four of whom experienced complete recovery. In three patients the
      eye remained amaurotic. No complications related to the operation were seen. The
      pterional orbital decompression described here represents an effective
      alternative approach for patients with sight-threatening retrobulbar hematoma,
      especially in cases where it is necessary to gain space for the orbit in addition
      to evacuating space-occupying blood or bone clots and treating neighbouring
      lesions. Immediate detection and adequate treatment of orbital hematomas is
      mandatory to achieve an acceptable outcome of eye function.

PMID- 12066471
TI  - [Heparin-induced thrombocytopenia as a complication of postoperative prevention
      of thromboembolism with unfractionated heparin/low molecular weight heparin after
      hip and knee prosthesis implantation].
AB  - AIM: With this prospective study we analysed the occurrence of a heparin-induced
      thrombocytopenia type II (hit type II) using unfractioned heparin (UFH) or low
      molecular-weight heparin (LMWH) as postoperative thrombosis prophylaxis after
      primary total hip or knee replacements. Furthermore the postoperative course of
      the platelet count with UFH and LMWH was investigated. MATERIAL AND METHODS: In a
      prospective study we looked at the platelet count of 504 primary endoprothesis
      patients until the 9. postoperative day. 252 patients got UFH (3-mal 5000 IE
      Liquemin), 252 patients got LMWH (Clexane 40 opd) as thrombosis prophylaxis.
      RESULTS: 5 patients of the UFH-group developed a HIT type II (incidence 2%; 95%
      confidence interval 0.7-4.5) after 9.8 (7-16) days. Within the LMWH-group we saw
      just one case (incidence 0.4%; 95%-confidence interval 0-2.1). The drop of the
      platelet count was on average 64% (40.9-81.6). Within the 498 patients without a
      HIT type II just 2 patients had a drop of the platelet count between the 5. and
      9. postoperative day of more than 15% referring to the preoperative value (24%
      and 33%). CONCLUSION: The incidence of a HIT type II after the use LMWH seems to
      be lesser than after the use of UFH. The postoperative platelet count shows a
      typical course after a total joint replacement. With deviations of that a HIT
      type II must be excluded.

PMID- 12066472
TI  - [Kapandji intramedullary wire osteosynthesis in proximal humeral fractures].
AB  - For operative treatment of proximal humeral fractures minimal invasive techniques
      reduce the risk of iatrogenic damage of blood supply and periarticular scarring.
      Reported preliminary results are encouraging. We present our experience achieved
      with an intramedullary wire fixation adapted from a report of Kapandji in 1989.
      Between 3/95 and 6/00 29 patients were treated with this technique at our
      institution. All received early functional treatment. 14 patients (average mean
      age 56 years at time of trauma) who had a minimum follow up of 24 months (mean
      36.4 months) and therefore allowed a preliminary conclusion regarding avascular
      head necrosis (AVN) were reexamined by use of the Constant Score and x-ray. We
      examined three unstable 2-part, four 3-part and seven 4-part fractures (5 of them
      valgus-impacted). The mean Constant Score at follow up was 70 points (31-86
      points). We saw one total collapse of the humeral head because of AVN. In one
      patient the distal end of the wires led to a skin irritation and had to be
      shortened. We observed no secondary fragment displacement or non-unions. In our
      hands, this technique offers good results, even in valgus-impacted 4-part
      fractures of the elderly and allows internal fixation in little displaced but
      unstable fractures with the benefit of early functional treatment instead of
      longer immobilization. Based on the experience with intramedullary wiring the
      previously performed technique using threading wires was abandoned and the
      indication for primary arthroplasty considerably influenced.

PMID- 12066473
TI  - [Comminuted radial head fractures. Initial experiences with a Judet radial head
      prosthesis].
AB  - PURPOSE OF THE STUDY: Comminuted fractures of the radial head represent a
      particular therapeutic problem. Due to characteristic complications the resection
      as well as the implantation of the Swanson-prothesis could not convince. MATERIAL
      AND METHODS: We applied the radial head prothesis of Judet in 16 cases (14 type
      IV and 4 type III by Mason). RESULTS: At the moment we survey the follow up of 15
      patients after 12 to 45 months (average 18.2), the evaluation was performed using
      the score of Radin and Riseborough and the score of Morrey. With the score of
      Radin and Riseborough we found in 7 cases good, in 6 case fair and in 2 case poor
      results. With the score of Morrey we found 2 excellent, 11 good and 1 fair and
      poor results. The radiological examination did not show an increase of the
      carrying angle of the elbow, an osteoporosis, a proximal migration of the radius
      and a distal radio-ulnar dissociation. CONCLUSION: Compared with resection or
      Swanson-prothesis the bipolar prothesis of Judet has definite advantages.

PMID- 12066474
TI  - [Computer-assisted drilling of the lower extremity. Technique and indications].
AB  - Computer assisted navigation-based surgery is a novel and interesting challenge
      for todays surgeons. One must however keep in mind, that the indications for
      these techniques (a) should be carefully considered, (b) used only if morbidity
      is not increased and (c) when previously problematic or inacurate surgical
      methods can be improved upon. This study reports that, using a non-invasive
      fixation method (FISCOFIX-Cast), lesions between the ankle- and knee-joints can
      be precisely localized, registered and treated. Due to the difficult access to
      lesions especially in the posterior areas of the talus, using conventional
      arthroscopic methods this procedure is very useful. Percutaneous retrograde
      drilling (cf. [6, 7, 9, 15, 20, 21]) spared the joint's cartilage in all cases.
      At the level of the knee joint we see the usefulness of this method for complex
      situations (cf. [12, 13]) requiring precise drilling.

PMID- 12066475
TI  - [Effect of short-distance spondylodesis of the thoracolumbar transition on
      neighboring facet joints. A biomechanical study].
AB  - This study was performed to investigate the range of motion and the forces on the
      facet joints that are neighboured to spondylodesis on thoracolumbar spine. We
      used a special spine testing device for a continuous application of pure moments
      in each direction. For measuring the ranges of motion we used a magnetic tracking
      device for measuring forces on facet joints we chose a direct measuring system of
      quartz crystal and prepared for investigation of the spine. The biomechanical
      testing was done on 18 human spinal specimen. We investigated the range of motion
      and the forces on facet joints in T11/12 and L2/3 segment with a maximal loading
      of 8 Nm in each direction (flexion, extension, lateral bending and rotation).
      This was done before and after double level dorsal instrumentation T12-L2 with an
      internal fixateur. Statistical analysis was performed using the paired t-test and
      the Wilcoxon test (p < 0.05). After double level instrumentation there were
      significant larger ranges of motion in flexion and extension and significant
      larger forces on facet joints in left lateral bending in the T11/12 segment. No
      significant differences were found in the L2/3 segment. Our findings could be an
      indication for changing in joints loading. This could be an explanation for early
      degenerative changes in spinal segments adjacent to spondylodesis. The results
      confirm the demand of short segment instrumentation and early remove of implants
      to keep influence as low as possible.

PMID- 12066476
TI  - [Injuries of the Chopart joint].

PMID- 12066477
TI  - [Traumatic coronary artery dissection after blunt thoracic trauma--a case
      report].
AB  - We present a case of cardiac infarction after blunt chest trauma. The 49-year-old
      patient suffered from severe angina and the ECG demonstrated a pattern of acute
      anterior wall myocardial infarction. Acute coronary angiography was performed
      showing complete occlusion of the left interventricular coronary artery due to
      dissection. An attempted revascularization by percutaneous transluminal coronary
      angioplasty failed and the patient was then submitted to bypass surgery. We
      conclude that possible heart injury should be considered in patients with blunt
      chest trauma to lead them to adequate therapy.

PMID- 12066478
TI  - [Complete brachial plexus paralysis caused by compartment syndrome in heroin
      intoxication].
AB  - We report the case of a young man with heroin intoxication. While deeply
      unconscious, he sustained a compartment syndrome of the arm and shoulder region
      leading to a lesion of the upper plexus. Immediate surgical decompression by
      fasciotomy incisions, intensive care treatment including hemofiltration to treat
      myoglobinemia, intense physical exercise, and mesh-grafting closure of the wounds
      soon led to unexpected recovery. The function of the arm was restored in such a
      way that the patient was able to intoxicate himself again. He needed intubation
      and ventilation but recovered uneventfully.

PMID- 12066479
TI  - [Isolated transverse fracture of the os triquetrum. Case report of a rare
      injury].
AB  - With the case of a 25 year old patient we will report of a rare injury, the
      isolated body fracture of a triquetrum bone. This kind of injury often happens in
      dorsalflected and ulnarducted hand position because of the anatomical position of
      the triquetral bone. The therapy of choice is conservative treatment with a volar
      splint for three to six weeks. Operation is only necessary in case of dislocation
      of a fragment [4]. Complications as an aseptic necrosis of a fragment is not
      reported. We found only one case of a pseudarthrosis [5]. Even in our case
      occurred a complete healing of the bone and a complete functional remission.

PMID- 12066480
TI  - [Supracondylar corrective osteotomy in post-traumatic cubitus varus. 3 cases in 2
      patients].
AB  - Supracondylar fractures of the humerus in childhood frequently result in cubitus
      varus deformity. Pain, functional impairment and cosmetic problems can request
      surgical correction. This is a report on an adult and on a mature child with such
      deformities. The boy had sustained three injuries with following bilateral
      cubitus varus and lengthening of one lower leg. Planning, surgical technique and
      outcome of the osteotomies are described. We should recommend the resection of a
      full wedge with two oblique osteotomies and internal fixation with two plates on
      either side of the humerus.

PMID- 12066481
TI  - [Recommendations for the expert witness on expert testimony].

PMID- 12066482
TI  - Cut from a dangerous mold.

PMID- 12066483
TI  - Expectations for a stronger literature.

PMID- 12066484
TI  - Influence of framework design on fracture strength of mandibular anterior all
      ceramic resin-bonded fixed partial dentures.
AB  - PURPOSE: The purpose of this in vitro study was to evaluate the influence of the
      framework design on the fracture strength of all-ceramic resin-bonded fixed
      partial dentures (RBFPD) in the mandibular incisor region. MATERIALS AND METHODS:
      Twenty-four aluminum oxide ceramic frameworks were copy milled with the Celay
      system, glass infiltrated, and veneered with feldspathic porcelain to replace a
      mandibular incisor. Forty-eight extracted human incisors were used as abutments
      by embedding them in a polyester resin. The master casts were fabricated
      according to a typical clinical case. The sandblasted restorations were bonded to
      the acid-etched abutment teeth with a composite resin. Twelve RBFPDs had a
      conventional two-retainer design, and 12 had a cantilevered single-retainer
      design. Subgroups of eight specimens were subjected to a quasistatic load in the
      direction of the long axis of the abutment teeth in a universal testing machine.
      Additional subgroups of four specimens were subjected under 0 degrees to dynamic
      loading of 25 N in a dual-axis chewing simulator. RESULTS: The mean fracture
      strengths under quasistatic loading were 313 N (SD 42) for the two-retainer
      design and 291 N (SD 100) for the single-retainer design. The mean cycles
      sustained by specimens subjected to dynamic loading at 25 N were 50,081 (SD
      42,705) for the two-retainer design and 297,099 (SD 508,439) for the single
      retainer design. There was no statistically significant influence of the
      framework design on the fracture strength of the restorations under quasistatic
      or dynamic loading. CONCLUSION: The clinical application of cantilevered all
      ceramic RBFPDs in the mandible may be an alternative to all-ceramic RBFPDs with
      two retainers.

PMID- 12066485
TI  - The reporting of randomized controlled trials in prosthodontics.
AB  - PURPOSE: This article evaluates the reporting of randomized controlled trials
      (RCT) in prosthodontics, excluding endosseous implant-based prosthetics.
      MATERIALS AND METHODS: Reports of RCTs published to the end of 2000 in any
      language were identified using a multilayered search strategy. The Cochrane Oral
      Health Group specialized register, Medline, and personal libraries were searched.
      Three researchers appraised the articles independently using guidelines following
      Jadad and CONSORT, complemented with an evaluation of the appropriateness of the
      reported statistics. RESULTS: Ninety-two reports of RCTs were evaluated, covering
      a wide spectrum of study hypotheses, topics, and issues within various
      prosthodontic domains. The interrater agreements on appraisal criteria were
      relatively high, with median kappa values ranging between 0.65 and 0.79. The
      reports were in general of poor methodologic quality. Randomization and
      procedures for concealment allocation were not described in 70% of the articles.
      The methods used to generate the random allocation sequence were not mentioned in
      82%. The methods used to implement the random allocation sequence, clarifying
      whether it was concealed until all interventions were assigned, was not mentioned
      in 94%. Reporting who generated allocation sequence, who enrolled patients, and
      who assigned participants to groups was not reported in 7%. Reasons for
      withdrawals were not given in 23% of the reports. No attempt at blinding was
      reported in 72%. Statistical analysis was not described in 6% of the papers,
      while these analyses were assessed as appropriate for 75%, unclear in 12%, and
      inappropriate in 7%. CONCLUSION: Few RCTs in prosthodontics are reported in
      accordance with contemporary guidelines for adequate reporting of trials.

PMID- 12066486
TI  - Shock absorbability and hardness of commercially available denture teeth.
AB  - PURPOSE: Composite resin teeth are more widely used than porcelain or acrylic
      resin teeth in the fabrication of removable dentures because of their high
      fracture toughness and high abrasion resistance. The purpose of this study was to
      evaluate the shock absorbability of commercially available artificial posterior
      teeth by the free drop-ball test with an accelerometer and to evaluate the
      Vickers hardness at the surface. MATERIALS AND METHODS: The tested artificial
      teeth included seven composite resin teeth, one acrylic resin tooth, and one
      porcelain tooth. Specimens were tested 50 hours after immersion in distilled
      water at 37 degrees C. The impact value and Vickers hardness were measured. A one
      way analysis of variance was used to analyzed the data (P = .05). RESULTS: The
      composite resin teeth showed an intermediate impact value between that of the
      acrylic resin tooth and the porcelain tooth. Among the artificial teeth
      investigated, the porcelain tooth showed the highest impact value. A significant
      difference in the impact value was observed between the porcelain tooth and the
      composite resin and acrylic resin teeth. However, no significant difference was
      observed among the composite resin teeth tested. A significant correlation was
      found between the impact values and the Vickers hardness of the artificial teeth.
      CONCLUSION: The present findings suggest that composite resin teeth and acrylic
      resin teeth have a higher shock absorbability than porcelain teeth.

PMID- 12066487
TI  - Effect of ceramic surface treatment on tensile bond strength to a resin cement.
AB  - PURPOSE: The objective of this study was to test the following hypotheses: (1)
      hydrofluoric acid (HF)-treated ceramic surfaces produce the highest tensile bond
      strength to resin cements, independent of the ceramic microstructure and
      composition; and (2) the tensile bond strength test is appropriate for analysis
      of interfacial adhesion for ceramic-bonded-to-resin systems. MATERIALS AND
      METHODS: Ceramic specimens were polished with 1-micron alumina abrasive and
      divided into four groups of 10 specimens for each of seven ceramic types. One of
      the following surface treatments was applied: (1) 10% ammonium bifluoride (ABF)
      for 1 minute; (2) 9.6% HF for 2 minutes; (3) 4% acidulated phosphate fluoride
      (APF) for 2 minutes; and (4) a silane coupling agent. The surface-treated areas
      were coated with an adhesive resin and bonded to a resin cement. Specimens were
      loaded to failure in tension using a testing machine. Tensile bond strength data
      were statistically analyzed, and fracture surfaces were examined to determine the
      mode of failure. RESULTS: Silane-treated surfaces showed statistically higher
      mean tensile bond strength values than surfaces treated with any etchant (HF,
      ABF, APF). HF produced statistically higher mean tensile bond strengths than ABF
      and APF. All failures occurred in the adhesion zone. CONCLUSION: The tensile bond
      strength test is adequate for analysis of the adhesive zone of resin-ceramic
      systems. The chemical adhesion produced by silane promoted higher mean bond
      strength values than the micromechanical retention produced by any etchant for
      the resin-ceramic systems used in this study.

PMID- 12066488
TI  - Spectral analysis of /s/ sound with changing angulation of the maxillary central
      incisors.
AB  - PURPOSE: The aim of the study was to measure the influence of the maxillary
      central incisors free from adaptation phenomena using spectral analysis.
      MATERIALS AND METHODS: The maxillary dentures of 18 subjects were duplicated. The
      central incisors were fixed in a pivoting appliance so that their position could
      be changed from labial to palatal direction. A mechanical push/pull cable enabled
      the incisor section to be handled extraorally. Connected to the control was a
      sound generator producing a sinus wave whose frequency was related to the central
      incisor angulation. This acoustic signal was recorded on one channel of a digital
      tape recorder. After calibration of the unit, the denture duplicate was inserted
      into the subject's mouth, and the signal of the /s/ sounds subsequently produced
      by the subject was recorded on the second channel during alteration of the
      inclination angle simultaneously with the generator signal. Spectral analysis was
      performed using a Kay Speech-Lab 4300B. RESULTS: Labial displacement in
      particular produced significant changes in spectral characteristics, with the
      lower boundary frequency of the /s/ sound being raised and the upper boundary
      frequency being reduced. CONCLUSION: Maxillary incisor position influences /s/
      sound production. Displacement of the maxillary incisors must be considered a
      cause of immediate changes in /s/ sound distortion. Therefore, denture teeth
      should be placed in the original tooth position as accurately as possible. Our
      results also indicate that neuromuscular reactions are more important for initial
      speech sound distortions than are aerodynamic changes in the anterior speech
      sound-producing areas.

PMID- 12066489
TI  - Mandibular overdentures: comparative evaluation of prosthodontic maintenance of
      three different implant systems during the first year of service.
AB  - PURPOSE: This prospective study evaluated the prosthodontic maintenance
      requirements during the first year of service of mandibular overdentures
      supported by two unsplinted implants using three different implant systems.
      MATERIALS AND METHODS: Seventy-two patients randomly allocated to three equal
      groups were each provided with a conventional complete maxillary denture and a
      mandibular overdenture supported by two unsplinted implants. A different implant
      system was used for each group (Steri-Oss, ITI, or Southern Implants), and their
      prosthodontic maintenance requirements were compared, primarily for the patrix
      and matrix. Additional maintenance categories recorded included any type of
      overdenture fracture, reline or remake of the overdenture, and maintenance of the
      maxillary denture. RESULTS: Sixty-eight percent of the patients, regardless of
      implant system, required prosthodontic maintenance in the first year, most
      commonly for the matrices. The Southern Implants matrices required less
      maintenance than those of Steri-Oss or ITI (P < .05). Additional overdenture
      maintenance was required by 28% of patients, irrespective of implant system. When
      all categories of prosthodontic maintenance were combined, there were no
      differences between implant groups. Evaluation of overall prosthodontic success
      using six-field tables revealed statistically significant differences between the
      three implant systems, with more ITI and Steri-Oss patients than Southern
      Implants patients requiring overdenture retreatment (repair). CONCLUSION: During
      the first year of service, the matrix maintenance requirements of Southern
      Implants were significantly lower than those of the ITI or Steri-Oss groups; this
      was reflected in the number of retreatment (repair) categories recorded. Although
      the three systems did not differ significantly for overall prosthodontic
      maintenance, both the Steri-Oss and the ITI titanium matrices showed problems of
      clinical significance.

PMID- 12066490
TI  - Effect of different artificial aging conditions on ceramic-composite bond
      strength.
AB  - PURPOSE: The purpose of this study was to evaluate the influence of different
      storage conditions on the bond strength of adhesive bonding systems to yttria
      partially stabilized zirconia ceramic. MATERIALS AND METHODS: Acrylic glass tubes
      filled with composite resin were bonded to ceramic disks. After sandblasting and
      ultrasonic cleansing of the ceramic samples, they were bonded using five bonding
      methods. Samples were tested for tensile bond strength following five different
      storage conditions: 3 days in distilled water at 37 degrees C, 31 days in
      distilled water at 37 degrees C, 37,500 thermocycles between 5 and 55 degrees C
      within 31 days, 150 days in distilled water at 37 degrees C, and 150 days in
      distilled water with 37,500 thermocycles performed at intervals. RESULTS: Mean
      resin bond strength values ranged from 7.7 to 41.9 MPa. There were statistically
      significant differences among groups, as revealed by the Kruskal-Wallis test.
      Some storage conditions influenced the resin bond strength statistically
      significantly, as revealed by the Wilcoxon rank sum test modified by Bonferroni
      Holm. CONCLUSION: Thermocycling had a much higher impact on the durability of the
      resin bond strength to zirconia ceramic than did water storage at a constant
      temperature.

PMID- 12066491
TI  - A multicenter interracial study of facial appearance. Part 1: A comparison of
      extraoral parameters.
AB  - PURPOSE: This study was undertaken to compare the facial appearance of patients
      from six racial groups (African American, Caucasian, Chinese, Hispanic, Japanese,
      and Korean) for interracial and/or gender differences and to determine if "norms"
      existed. MATERIALS AND METHODS: A total of 253 subjects (144 men and 109 women)
      ranging in age from 18 to 41 years (mean age 26.5 years) were evaluated using a
      standardized protocol. The data were collected and analyzed to establish
      reference ranges for seven frontal and six profile extraoral parameters. Mean
      scores were compared by race and gender using a one-way analysis of variance,
      followed by the Tukey-Kramer test for honestly significant difference when
      statistically significant differences were found (P < .05). RESULTS: There were
      no significant differences for any of the seven frontal or six profile extraoral
      parameters between men and women. No significant differences were found between
      racial groups for five of the seven frontal and one of the six profile extraoral
      parameters. CONCLUSION: Most of the frontal facial parameters and one profile
      extraoral parameter might be considered norms for male and female patients of
      different ethnic origins. Additional research with larger patient populations
      would be needed to confirm or refute these trends.

PMID- 12066492
TI  - A multicenter interracial study of facial appearance. Part 2: A comparison of
      intraoral parameters.
AB  - PURPOSE: This article compares interracial or gender differences of six intraoral
      dental parameters among six racial groups (African American, Caucasian, Chinese,
      Hispanic, Japanese, and Korean). MATERIALS AND METHODS: The same 253 patients
      participating in part 1 were included in this portion of the study to evaluate
      six intraoral parameters. The data were collected and analyzed using a one-way
      analysis of variance, followed by the Tukey-Kramer test for honestly significant
      difference when statistically significant differences were found (P < .05).
      RESULTS: Women displayed significantly more gingival tissue in four of the six
      races, and African Americans displayed significantly more gingival tissue than
      any other race. Women had significantly more missing teeth than men in three of
      the six races studied. Japanese subjects had significantly fewer missing teeth
      and smaller maxillary central incisors than all other groups except Caucasians.
      Women had significantly narrower maxillary central incisors in three of the
      races. There was a significantly higher prevalence of Angle Class III
      relationships in Chinese subjects. The Japanese had significantly more Class II
      molar relationships than other races. CONCLUSION: Racial and gender differences
      were found in gingival tissue display, the number of missing teeth, maxillary
      right central incisor crown width, and Angle molar classification, but not in the
      amount of vertical or horizontal overlap of the anterior teeth.

PMID- 12066493
TI  - Articulator-related registration--a simple concept for minimizing eccentric
      occlusal errors in the articulator.
AB  - PURPOSE: The purpose of this study was to develop an easy-to-use procedure for
      individual registration and to test its accuracy. Unlike common principles, the
      method should be based on a transfer of the articulator geometry to the patient.
      MATERIALS AND METHODS: The system consists of an articulator holding a bite plate
      in a standard position. The bite plate connects to an electronic recording
      system, which transfers the articulator's condylar points virtually to the
      patient's mandible by a centric relation record. The trajectories of the
      transferred points are recorded during mandibular protrusions and laterotrusions.
      From the trajectories, sagittal condylar and Bennett angles are measured and are
      adjusted at the articulator after mounting of the casts via the bite plate. Using
      a mechanical testing device, the accuracy of the measured angles was examined by
      comparison with preset values varying from 10 to 60 degrees (condylar angle) and
      from 0 to 40 degrees (Bennett angle) in 10-degree increments. RESULTS: The mean
      deviations of measured condylar angles from preset values ranged between 1.5 and
      0 degrees. The mean deviations of the Bennett angles ranged from -0.5 to -1.3
      degrees. CONCLUSION: The transfer of articulator geometry to the patient reduces
      the number of individual parameters necessary to imitate jaw motion to the
      condylar and Bennett angles. This leads to a significant simplification in
      registration and cast transfer. Since the required parameters are recorded with
      high accuracy, the method could be an alternative to traditional sophisticated
      instrumental registration.

PMID- 12066494
TI  - Influence of mandibular residual ridge shape on masticatory efficiency in
      complete denture wearers.
AB  - PURPOSE: The purpose of this study was to investigate the influence of mandibular
      residual ridge shape on masticatory efficiency in complete denture wearers.
      MATERIALS AND METHODS: Twenty-eight complete denture wearers (mean age 75.6
      years, SD 4.8) who received their complete denture treatment by one of the
      authors and had no troubles in daily use were selected. The mandibular residual
      ridge was evaluated by using a replica of the ridge obtained with heavy-body
      silicone impression material. The basal area of the replica was measured by a
      digitizer. The volume and the height of the replica were calculated. Masticatory
      efficiency in each subject was measured by the sieving method. RESULTS: There was
      a significant correlation between the masticatory efficiency and basal area,
      volume, and height of the residual ridge. The basal area showed the strongest
      correlation. CONCLUSION: The basal area of the denture foundation greatly
      influenced the masticatory efficiency, suggesting that the masticatory efficiency
      in complete denture wearers was limited by their own residual ridges and that
      clinicians should inform their patients about the limitation of the recovery of
      masticatory ability before the beginning of denture treatment.

PMID- 12066495
TI  - Clinical study on the reasons for and location of failures of metal-ceramic
      restorations and survival of repairs.
AB  - PURPOSE: A recently introduced technique, the Cojet system, using SiOx (Al2O3
      coated with silisic acid), provides ultrafine mechanical retention by
      sandblasting, as well as a chemicophysical bond between the metal-ceramic and the
      composite resin. This study determined the reasons for and locations of failures
      of metal-ceramic restorations and evaluated the survival of the intraoral silica
      coating system used for the repair of failed restorations. MATERIALS AND METHODS:
      A total of 153 patients possessing 289 fractured crowns were involved in this
      study; 255 of these fractures were on fixed partial dentures, whereas 34 were on
      single crowns. The mean observation period was 34.6 months. The materials used
      for the repair process were ESPE-Sil for silane; Visiogem, Sinfony, and
      Dentacolor as opaquers; and Pertac II Aplitip, Sinfony, and Charisma as repairing
      composite resins. RESULTS: The majority of the failures (65%) occurred in the
      anterior region. Sixty percent of the failures were observed at the labial, 27%
      at the buccal, 5% at the incisal, and 8% at the occlusal regions. The fractures
      were mainly in the maxilla (75%), predominantly at the labial surface. The
      overall cumulative survival rates of the repairs (89%) showed that the first
      failures happened mostly from 1 week to 3 months after the repair, without any
      difference between the composite resins. CONCLUSION: The original failures
      happened mainly during chewing function or because of accidents, iatrogenic
      factors, and surgical operations, whereas secondary failures after repair using
      intraoral silica coating and composite resin were due to trauma, chewing
      function, or lack of rubber dam application.

PMID- 12066496
TI  - Immediate implant-supported oral rehabilitation using a photocurable plastic
      skull model and laser welding. A technical note on the screw-retained type: Part
      1.
AB  - PURPOSE: This article describes a new procedure for immediate implant-supported
      oral rehabilitation using a photocurable resin skull model and a laser-welding
      apparatus. MATERIALS AND METHODS: Preoperatively, the framework was fabricated on
      a photocurable resin skull model produced from a CT scan and individually
      designed guide template. The implants were immediately placed using the guide
      template; laser welding connected the components of framework. RESULTS: Despite
      the custom-made prosthesis, the total treatment from implant placement to
      superstructure placement can be completed within only 1 day. CONCLUSION: This
      procedure for immediate implant-supported oral rehabilitation using a
      photocurable resin skull model and a laser-welding apparatus may be useful for
      any implant system and patient.

PMID- 12066497
TI  - The science of anxiety. Why do we worry ourselves sick? Because the brain is
      hardwired for fear, and sometimes it short-circuits.

PMID- 12066498
TI  - The little antibody that could.

PMID- 12066499
TI  - 12 steps for E-mail addicts.

PMID- 12066500
TI  - What they're seeing.

PMID- 12066501
TI  - The hunger artists.

PMID- 12066502
TI  - [Risk improves effectiveness. Proper administration of platelet aggregation
      inhibitors].

PMID- 12066503
TI  - [Botulinum toxin in migraine. Acupuncture is cheaper].

PMID- 12066504
TI  - [Overlooked endocrine emergency. For hypoglycemia referral to psychiatry].

PMID- 12066505
TI  - [Heart failure. Are baths contraindicated? (interview by Dr. Ulrich Scharmer)].

PMID- 12066506
TI  - [From conjunctivitis to glaucoma. When is a red eye an alarm signal?].
AB  - A red eye is mostly a relatively harmless sign of simple conjunctivitis. Viral
      conjunctivitis may be extremely contagious. If no improvement is seen after ten
      days of treatment, referral to an ophthalmologist is indicated. Local
      corticosteroids and local anesthetics must not be prescribed. The patient should
      also be referred to an ophthalmologist when the red eye is chronic or recurrent,
      and when a unilateral red eye is associated with severe pain and vomiting
      (suspicious for acute glaucoma!), or generally when severe pain or impairment of
      sight, indicative of corneal infiltration or a hypopyon, presents. The diagnostic
      use of fluorescein to stain the cornea and any alteration of corneal transparency
      also belong in the hands of the ophthalmologist.

PMID- 12066507
TI  - [Dry eyes, blurred vision, foreign body sensation. Does your patient need
      artificial tears?].

PMID- 12066509
TI  - [Acetylsalicylic acid for cardiovascular risk patients. Placebo or life safer?].

PMID- 12066508
TI  - [Antibiotic eye ointment with vitamin B and bandage. This helps
      keratoconjunctivitis photoelectrica].

PMID- 12066510
TI  - [Quincke edema as general practice emergency. Allergic or genetic--this has
      therapeutic relevance!].

PMID- 12066511
TI  - [This also applies to diabetic patients: no fear of beta blockers].

PMID- 12066512
TI  - [Blood pressure increases with waist circumference].

PMID- 12066513
TI  - [Principles for general ultrasound practice. Urinary tract obstructions].

PMID- 12066516
TI  - [Don't allow the aut-idem regulation intimidate you. Act like the chancelor:
      continue working with steady hand].

PMID- 12066514
TI  - [Pilot study with 5-HT3 antagonists. Good outcome in fibromyalgia pain].

PMID- 12066515
TI  - [70-year-old farmer with increasing exertional dyspnea. Dyspnea in the barn].

PMID- 12066517
TI  - [We should manage patients "according to regulations of medical art". But the
      regulations are printed nowhere].

PMID- 12066518
TI  - [Early tick-borne meningoencephalitis infections occur already in March.
      Pediatric vaccine is available again].

PMID- 12066519
TI  - [Goiter and nodules in the thyroid gland. 15 million patients with undetected
      illness].

PMID- 12066521
TI  - [ACE inhibition in tissues. Decisive for prognosis?].

PMID- 12066520
TI  - [Chronic pain of the musculoskeletal system. Make your patients move!].

PMID- 12066522
TI  - [Patient is always tired and unconcentrated. Liver damage can be the cause].

PMID- 12066523
TI  - [Phthisa-school as a way of psychosocial correction of pulmonary tuberculosis].
AB  - Pulmonary tuberculosis leads to structural personality changes, impairs
      interpersonal interaction, incompliance of personal hygiene. To develop
      educational methods, 253 patients with pulmonary tuberculosis were examined. To
      conduct a special cycle including 6 classes called by the author as a Phthisa
      School is optimal for patient-physician contact and cooperation. Correction of
      altered personality traits in patients with pulmonary tuberculosis within the
      framework of the educational curriculum allows this to be considered as a way of
      sociopsychological correction.

PMID- 12066525
TI  - [Ways of overcoming drug resistance in patients with pulmonary tuberculosis].
AB  - To elucidate the combined effect of surfactants and antituberculous drugs, the
      surfactant myrastimine was tested. Two series of sputum cultures with multidrug
      resistant Mycobacterium tuberculosis (MBT) strains were made. The experimental
      results confirmed that myramistine noticeably enhanced the sensitivity of
      multidrug-resistant MBT strains to antituberculous agents. The use of
      endobronchial and intracavernous myramistine in combination with antituberculous
      agents to patients with destructive pulmonary tuberculosis caused by multidrug
      resistant MBT strains reduced the latter's resistance to antibiotics, cured
      tubendobronchitis in most patients, created conditions for obliteration of the
      cavernous cavity. Positive changes are noted in the first 4 months after the
      initiation of therapy, which can prepare patients for surgical treatment more
      rapidly.

PMID- 12066524
TI  - [The analysis of cases of delayed diagnosis of tuberculosis among the population
      of the Cheliabisk district].
AB  - There was a steady-state rise in tuberculosis morbidity in the Chelyabinsk Region
      in the 1990s. At the same time, the number of patients whose disease is untimely
      detected was on the increase and in some cases the disease is found just at
      autopsy. These facts result from the lower efficiency of tuberculosis controlling
      measures, from low training of general physicians in detecting and diagnosing
      tuberculosis, and from failure to meet the standards for examining all those who
      have fallen ill.

PMID- 12066526
TI  - [Genetic aspects of tuberculous infection in adolescents].
AB  - Comparative study of the distribution of antigens of HLA-A, B, and C, as well as
      somato- and phenotype in 234 adolescents has revealed that HLA-A11 and HLA-B12
      antigens may indicate a predisposition to tuberculosis and HLA-A28, HLA-B8, and
      HLA-B51 antigens are involved in its prevention. It has been found that there is
      predominance of persons having severe forms of somatotype (dolychobrachymorphic)
      and that there is also a high phenotype stigmatization in adolescents with
      different manifestations of tuberculous infection.

PMID- 12066527
TI  - [The use of immunomodulator likopid in the combined treatment pulmonary
      tuberculosis].
AB  - Licopid is a synthetic analogue of a cell wall component of all bacteria. The
      monocytic macrophageal system is the main target of licopid's action. Addition of
      the immunomodulator to combined therapy for patients with pulmonary tuberculosis
      in order to enhance phagocytic activity exerted a marked clinical effect appeared
      as ceased bacterial isolation in 80% of the patients, a fall in the amount of
      purulent sputum, no symptoms of intoxication following 2-3 weeks, accelerated
      resolution of infiltrative changes. The positive clinical effect coincided with
      the immunological one manifested as increases in the absolute counts of CD3+CD4+
      and CD3+CD8+ cells, in the absorptive and bactericidal functions of phagocytes.
      Such effects were not observed in patients receiving routine treatment. Licopid
      is recommended for supplementation to the combined treatment regimen for
      pulmonary tuberculosis.

PMID- 12066528
TI  - [Surgical treatment of fibro-cavernous tuberculosis].

PMID- 12066529
TI  - [Comparative evaluation of the efficiency of trans-sternal occlusion of the main
      bronchus in the treatment of disseminated complicated pulmonary tuberculosis].

PMID- 12066530
TI  - [Antitubercular care among the Chukotka Autonomic Distric population].
AB  - Analysis of antituberculosis care to the Chukotka Autonomic District population
      in 1994-1999 suggests that despite economic difficulties, there was a continuous
      reduction in the major tuberculosis parameters. This may be accounted for by
      inadequate detection of tuberculosis among aborigines and by low contacts with
      comers. The resources created in the past years have been exhausted and, if
      urgent measures are not taken, there will be a rise in tuberculosis morbidity
      rates in the district.

PMID- 12066531
TI  - [Value of thoracoplasty and causes of its inefficiency in destructive pulmonary
      tuberculosis].

PMID- 12066532
TI  - [Laser therapy in the combined treatment of renal tuberculosis].

PMID- 12066533
TI  - [Clinical features of male genital tuberculosis in Uzbekistan].
AB  - The clinical course of genital tuberculosis was studied in 126 males treated at
      the Phthisiourology Unit (in 1992-1997). Case histories of 505 more patients (in
      1974-1988) were examined. It was ascertained that there was an increase in the
      incidence of this disease in an old age group (51-60 years) from 9.7% (1974-1988)
      to 21.4% (1992-1997) and a reduction in a young age group (31-40 years) from 33.1
      to 22.2%, respectively. Most (92.8%) patients aged 21 to 60 years had the
      greatest manifestations of the disease at the present-day stage while those
      (92.5%) aged 21 to 50 years fell ill with this disease in 1974-1988. There was an
      increase in the incidence of fistulous tuberculosis of the male genitals from
      8.7% (in 1974-1988) to 20.6% (in 1992-1997), which confirms altered pathomorphism
      and deteriorated epidemiological situation. The diagnostic minimum which may
      render a great assistance to general practitioners in timely recognizing the
      disease and referring patients with this disease to a specialized facility.

PMID- 12066534
TI  - [Abnormal changes in the upper digestive tract in patients with bronchial
      asthma].
AB  - The specific features of digestive tract abnormalities were studied in 187
      patients with bronchial asthma (BA) in the presence of reflux esophagitis (RE). A
      control group comprised 50 healthy individuals of both sexes who had no signs of
      bronchopulmonary diseases. Morphofunctional changes in the mucosa of the upper
      digestive tract were detected in 77.54% of the patients. Concurrent digestive and
      respiratory diseases lead to mutual burdening syndrome. Microaspiration in RE
      provokes bronchial exacerbations both in an asthmatic attack and at remission by
      resulting in progressive BA. Early diagnosis of an occult digestive tract
      abnormality may be made only when a complex of ultrasound and X-ray endoscopic
      studies is applied.

PMID- 12066535
TI  - [Some metabolic characteristics of circulating phagocytes in patients with
      different types of pulmonary tuberculosis].
AB  - Before and 2 and 3 months after chemotherapy, spontaneous and BCG-stimulated
      nitroblue tetrazolium (NBT) tests, superoxide dismutase (SOD) and catalase
      activities, the levels of malonic dialdehyde (MDA) and platelet activation factor
      (PAF) in isolated mononuclear cells and neutrophils were estimated in 169
      patients with different forms of pulmonary tuberculosis. Before treatment, in the
      patients the monocytic bactericidal potential assessed by NBT test parameters was
      found to increase, but the neutrophilic one reduced due to their basal
      overirritation. All other test parameters were higher in both types of cells. The
      magnitude and balance of changes were interrelated to the onset and nature of the
      process. Following 3 months of treatment, the bactericidal potential increased
      much more in the monocytes and returned to normal values if the changes in the
      processes were favourable. In both types of the cells, SOD activity became normal
      to normal values, MDA levels were maintained in the normal range due to the a
      preserved enhancement in catalase activity. PAF remained in the upper normal
      range. Both types of the cells showed drastically increased levels of MDA and
      drastically decreased PAF levels with progression due to therapy.

PMID- 12066536
TI  - [The activity of adenosine deaminase and its isoenzymes in patients with
      different forms of pulmonary tuberculosis].
AB  - An examination of 144 patients with different forms of pulmonary tuberculosis has
      revealed that serum adenosine deaminase (ADA) has a higher activity in the
      patients than in healthy individuals (a control group). The level of its activity
      is in proportion to the severity of a pulmonary process and achieves its peak in
      caseous pneumonia. In infiltrative tuberculosis, there is a direct relationship
      between the activity of ADA, the number of involved segments and bacterial
      isolation. The activity of ADA has been shown to be increased by its isoenzyme
      ADA-2. The unidirectional changes in the activity of ADA and the clinical and X
      ray characteristics of the disease treated with antituberculous drugs make it
      possible to recommend this parameter as an additional criterion for evaluating
      the specific features of a process in the lung and the adequacy of therapy.

PMID- 12066537
TI  - [Tuberculous IgE antibodies. Part II. Study of its concentrations in different
      forms of tuberculosis].
AB  - Tuberculosis-afflicted lung are infiltrated by two functionally types of
      lymphocytes, which presumably counteract with each other by producing
      proinflammatory (type 1) and anti-inflammatory (type 2) cytokines. It is held
      that irregular sequestration of antigen into different compartments of the lung
      may lead to preferential activation of T-helper 1 or T-helper 2 lymphocytes.
      Unlike IgE antibodies, specific tuberculosis IgE antibodies are seen only in
      tuberculosis infection. The mean values of IgE antibodies in tuberculosis (7.661
      +/- 0.849 IU/ml) are significantly greater than those in other pulmonary diseases
      (1.768 +/- 0.116 IU/ml). Low concentrations of tuberculosis IgE antibodies in
      persons with a marked hyperergic response to tuberculin (1.808 +/- 0.097 IU/ml)
      are of importance. Significant concentrations of mycobacterial IgE antibodies are
      mainly detected in fibrocavernous (14.56 +/- 1.11 IU/ml), infiltrative (10.10 +/-
      1.08 IU/ml), peripheral lymph nodal (10.53 +/- 1.09 IU/ml) tuberculosis rather
      than intrathoracic lymph nodal tuberculosis (4.555 +/- 0.340 IU/ml). There is a
      particularly considerable increase in specific IgE antibodies in a phase of decay
      (15.98 +/- 1.64 IU/ml) and infiltration (12.66 +/- 1.08 IU/ml). These groups also
      show a concurrent rise in tuberculosis IgG antibodies, which nevertheless
      disagree with the increase of IgE (the correlation coefficient is 0.599).

PMID- 12066538
TI  - [Fatty acid lipid spectrum in the expired air condensate of persons exposed to
      moderate-dosage ionizing radiation at the Chernobyl atomic power station].
AB  - The fatty acid spectrum of lipids was examined in the expired air condensate
      (EAC) in health persons and in Chernobyl accident liquidators. Exposure to
      radiation even to small dosage may cause changes in the fatty acid composition of
      lipids in the surfactant of the lung and promote to the occurrence of
      inflammatory respiratory diseases. The changes found in the EAC fatty acid lipid
      spectrum, which may reflect the status of a pulmonary surfactant, may be used to
      identify patients with respiratory diseases and be borne in mind in treating
      these patients.

PMID- 12066540
TI  - [Macrophages-Mycobacterium interaction during a microorganism's response to
      tuberculous infection].

PMID- 12066539
TI  - [Molecular genetic characteristics of Mycobacterium tuberculosis isolated from
      patients operated on for pulmonary tuberculosis].
AB  - The RFLP-IS6110 assay was used to genotype 67 Mycobacterium tuberculosis isolated
      from different specimens (including intraoperative ones) of 24 patients operated
      on for chronic progressive pulmonary tuberculosis who lived in north-western
      Russia. More than half (53%) of 17 types of RFLP profiles of isolates are
      identical and typical of M. tuberculosis of the Beijing family. Comparing the
      results of isolate genotyping with clinical, microbiological, and
      pathomorphological findings allows cases of endogenous reactivation to be
      differentiated from exogenous (nosocomial, in particular) reinfection in
      recurrence. Beijing genotype strains are shown to cause more severe unarrested
      course of drug-resistant fibrocavernous tuberculosis. At the same time such
      strains are more frequently detected in relatively young persons with a shorter
      duration of the disease, which reflects current clonal Beijing genotype
      dissemination that present a severe epidemiological hazard.

PMID- 12066541
TI  - [Tuberculosis mortality in the USSR from 1903 to 1924].

PMID- 12066542
TI  - [Epidemiology of tuberculosis in Vladivostok].
AB  - In the early 1990s there was a great change in the tuberculosis situation in
      Vladivostok. Since 1992, the average total tuberculosis morbidity has increased
      by 22.7% and in 2000 it amounted to 91.0 per 100,000. Its morbidity among
      children increased by 90% in the same period. The morbidity due to tuberculosis
      in its risk groups is several times higher than that in the general population.
      The reasons for this rise were socioeconomic crisis, high population density in
      Vladivostok, intensive, virtually uncontrolled migration. The basic methods of
      detection of tuberculosis in Vladivostok, as in Russia as a whole, remain as
      follows: fluorography, bacteriology, and tuberculin diagnosis. The efficiency of
      each method is associated with the organization and financing of activities in
      detecting and with the potentialities of methods, personnel qualification. It is
      necessary to pay attention to the detection of tuberculosis in the risk groups,
      by making their register in order to enhance the effectiveness and to reduce the
      cost of existing methods. Strict control and management of a migration process
      and solution of social problems are needed.

PMID- 12066543
TI  - [Some aspects of tuberculosis prophylaxis care under current socioeconomic
      conditions].
AB  - The paper deals with 4-year work of a tuberculosis dispensary that serves over 1
      million residents of Moscow. It presents the causes of late detection of
      tuberculosis, the specific features of the socioeconomic status and those of the
      clinical picture of the disease in relation to the "channel" of detection, as
      well as the structure of identification of Mycobacterium tuberculosis resistance
      in new and old cases of tuberculosis and also analyzes the efficacy of treatment
      by the DOTS methods in new cases of pulmonary tuberculosis who have complete a
      full 6-month treatment course.

PMID- 12066544
TI  - [Hemodynamic measurements with the Swan-Ganz catheter (in the pulmonary artery)
      in severe preeclampsia patients].
AB  - We compared the results of Swan-Ganz measurements in 11 preeclamptic women and
      report of the hemodynamic profile in severe preeclampsia. Measurements were
      performed between 28-36 weeks of gestation.

PMID- 12066545
TI  - [Resuscitation in very low birth weight and extremely low birth weight newborns
      in the delivery room].
AB  - THE AIM: Of the study is to discuss the need of delivery room cardio-pulmonal
      resuscitation (DR-CPR) in VLBW and ELBW infants and intensity, to determine its
      prognostic significance for the neonatal outcomes, and the influence of some
      perinatal criteria. MATERIALS AND METHODS: A retrospective study is performed in
      University Maternity Hospital: Maichin Dom", for the years 1998-1999 including:
      61 ELBW (500-999 g) and 122 VLBW (1000-1499 g). Excluded are infants with great
      malformations. RESULTS: There were 54% survivors in the ELBW and 86.1% in the
      VLBW group. 1-st min Apgar scores were significantly lower in the ELBW-group 3.5
      +/- 1.9 in comparison to the VLBW: 4.9 +/- 1.9 = pH from umbilical artery were
      lower too: 7.19 +/- 0.16 and 7.24 +/- 0.14 respectively. From 12 ELBW babies with
      cord arterial pH < 7.1 survived only 3, but all 3 with pH < 7.0 died; 8 from 10
      VLBW babies with pH < 7.1 survived. Intubation rates were as followed: ELBW group
      -82%, 70% in the first 5 min; VLBW group--57% and 34% respectively. Adrenalin
      and/or chest compression received 6 ELBW infants, 5 of who died and 4 had severe
      IVH. The same resuscitation received 8 VLBW babies, 4 of who died and 2 survivors
      had 3-4 grade IVH. Any grade of IVH occurred in 65% of ELBW and in 44% of VLBW
      infants. Severe IVH was seen in 37% and 16% respectively. Overall, survivors with
      grade 3-4 IVH were 15% among the ELBW group and 7.6% among the VLBW. CONCLUSIONS:
      Birth weight and gestational age are the most important factors, determining the
      intensity of DR-CPR and the prognosis in newborns of < 1500 g. Low Apgar scores,
      cord arterial pH < 7.10, the need of Adrenaline application and/or chest
      compression by DR-CPR are reliable prognostic criteria for death and poor
      nevrodevelopmental outcome.

PMID- 12066546
TI  - [Problems and outcome in extremely low birth weight newborns, depending on the
      mode of delivery].
AB  - THE AIM: Of this study is to determine the impact of the mode of delivery on
      survival, morbidity and prognosis of ELBW and extremely low gestational age
      (ELGA) newborns. METHODS: The retrospective review includes ELBW and ELGA infants
      born at the State maternity hospital "Maichin dom" Sofia from 1997 to 1999. These
      are 95 newborns divided into two groups: 31 born by Cesarean section (C. s.), and
      64--per vias naturals (p. v. n.) with subgroups: 42--vertex, 22--breech delivery.
      Resuscitation is similar in all groups, according the routine practice. They are
      compared by the following indexes: rate of survival, Apgar scores at the 1-st and
      at the 5-th min, pH from the umbilical artery (u. a.), rate of the
      intraventricular hemorrhages (IVH) and periventricular leukomalacia (PVL), and
      early nevrodevelopmental outcome. RESULTS: The birth weight of all babies
      includes ranges from 500 to 999 g and the gestational age (g. a.) is > 24 weeks
      of gestation. There is no statistically significant difference (p < 0.05)
      according birth weight, pathology and treatment of the mother, between the two
      groups. In the C. s. group 17 babies survived (55%) while in p. v. n. 30 survived
      (47%), the worst was survival between the babies, delivered in breech
      presentation--7 (32%), p < 0.05. There is no significant difference between pH
      and BE from u. a., but Apgar scores are worse in the breech group, p < 0.05. The
      incidence of all grades IVH and PVL is almost the same, but there is a
      significant difference in the incidence of severe, grade 3 and 4 IVH and PVL (19%
      in C. s. group versus 48% p. v. n. group). The survivors with severe IVH are 57%
      among the breech delivered (p < 0.05) compared with respectively 33% and 26%
      among c. s. and vertex delivered groups. A CONCLUSION: Is made that C. s.
      provides better chances for a safe survival in ELBW and ELGA newborns and better
      prognosis for neurodevelopmental outcome. With the worst prognosis are the breech
      delivered ELBW babies.

PMID- 12066547
TI  - [Drug treatment of tubal pregnancy with methotrexate, with an analysis of 5
      cases].
AB  - The authors present 5 cases of ectopic pregnancy, treated successfully with
      Methotrexate. Followed are the levels of beta-fraction of human chorionic
      gonadotropin. Later on, in two of the patients developed intrauterine pregnancy,
      which terminated successfully with the delivery of healthy term infants.

PMID- 12066548
TI  - [Second trimester Down syndrome serum screening--results from a pilot study].
AB  - The results from a pilot prospective study--second trimester Down syndrome [DS]
      serum screening between 15 and 21 w.g. with two markers (alpha-fetoprotein and
      free bb-hCG)--were summarised. Sensitivity, false-positive rate [FPR], positive
      predictive value [PPV] of the screen positive and negative predictive value [NPV]
      of the screen negative result for the sbgroups II and below 35 years of age were
      analysed. The uptake for invasive prenatal testing in screen positive patients
      and the percentage of terminated pregnancies with prenatally diagnosed DS fetuses
      as well as the ratio "lost unaffected pregnancies/1 DS fetus diagnosed
      antenatally" were also calculated. High sensitivity of the DS serum screening was
      achieved--75% and 87.5% in the subgroups below and II the age of 35 respectively
      with 6.6 and 31.7% FPR. With higher DS age risk the PPV of the screen positive
      test was higher and the NPV of the screen negative result--lower. The percentage
      of invasive prenatal testing in screen positive patients was high (average 83.4%)
      without significant differences in the two age subgroups. Pregnancy was
      terminated in all cases with antenatally diagnosed DS fetuses. The ratio "lost
      unaffected pregnancies/1 DS fetus diagnosed antenatally" for serum screening was
      lower compared to the same ratio when screening by age. The results from our
      pilot study (serum screening sensitivity and FPR, uptake for invasive testing in
      screen-positive cases) are comparable to the ones reported in literature. This is
      an important prerequisite for introduction of mass DS screening for our
      population.

PMID- 12066549
TI  - [Hysteroscopic ablation of the endometrium in cases of dysfunctional uterine
      bleeding--advantage of preparations including zoladex].
AB  - Hysteroscopic endometrial ablation (HEA) is a new alternative for patients with
      dysfunctional uterine bleeding (DUB), resistant to medical treatment. The
      relatively thin endometrium is a big advantage at the time of operation. In this
      article the results of an initial series of hysteroscopic operations (HEA) are
      given--as a whole and depending on preoperative treatment with GnRH-agonist.
      Seventeen patients with DUB underwent HEA. Six of them were pretreated with
      Goserelin acetate (Zoladex 3.6 mg, Astra Zeneca) two subcutaneous application at
      28 days interval. The other 11 women were operated in the early postmenstrual
      period without medical pretreatment. Comparison was made between the two groups
      regarding preoperative endometrial thickness, operative time, operative
      complications, duration of hospital stay, change of the menstrual pattern after 6
      and 12 months. Results showed 41.2% achievement of persistent amenorrhoea in
      patients as a whole (62.7% in the Zoladex group and 27.2% in the untreated
      group). Better results in the patients with Zoladex pretreatment (shorter
      operative time, higher incidence of amenorrhoea, patient's higher evaluation of
      the operation) can be explained with the reduced endometrial thickness at the
      time procedure. The authors consider the hysteroscopic roller-ball endometrial
      ablation as an upto-date cost-effective method for treatment of DUB. The method
      is quick, with very low incidence of complications, easy toleration, immediately
      recovery of the patient and the only possibility for women with high
      anaesthesiologic and operative risk. Two depot-doses of Zoladex before
      hysteroscopy lead to better intra- and postoperative results.

PMID- 12066550
TI  - [Human papilloma virus (HPV) infection and its relationship with central intra
      epithelial neoplasia (CIN)].
AB  - HPV (Human papillomavirus) infection is strongly associated and is the main cause
      of cervical cancer. The main target for HPV viruses is the cervical
      transformation zone. In our work infection with HPV 18 and HPV 16 as also other
      types of viruses were investigated in 15 patients by taking biopsies. Before hand
      the patients were signalized by cytology as well as all of them were
      colposcopically examined. The samples were examined immunohistochemically in the
      laboratory at the Specialized Hospital for Active Treatment in Oncology. Nine out
      of 15 patients /60%/ were found positive for HPV-16, five /33%/ were found
      positive for HPV-18 and 1 /6.6%/ were infected with both HPV types. Our method is
      very sensitive and practical for determining at very high risk of developing HPV
      connected cervical cancer.

PMID- 12066551
TI  - [Adjuvant therapy during the administration of GnRH agonists].

PMID- 12066552
TI  - [Scientific basis of the theories on endometriosis].

PMID- 12066553
TI  - [Oral contraceptives and the risk of venous thromboembolism].

PMID- 12066554
TI  - [Acute renal insufficiency during pregnancy with acute pancreatitis].
AB  - According to current data the incidence of acute pancreatitis is from 1:1000 to
      1:5000. Symptoms vary a lot, one of rare but most severe complications being
      acute renal failure. The case is a 24-year-old pregnant patients--30-th
      gestational week with symptoms of acute pancreatitis based most probably on
      hereditary hypertriglyceridemia and hypercholesterolemia. Parallel to acute
      inflammation of pancrease a hypercoagulation syndrome developed. It is possible
      that acute renal failure was caused by active thrombus formation. Because of
      danger for the life of mother and baby, an urgency preterm Cesarean Section was
      performed. Resussitation post-surgery care and drug therapy (lowmolecular
      anticoagulants, antibiotics, spasmolytics and analgetics, protease--inhibitors,
      inhibitors of protome pump, regulators and inhibitors of pancreas secretion
      normalize renal and pancreatic function if based on special dietary regimr.
      Coagulation status also normalizes.

PMID- 12066555
TI  - [Fatal outcome in peripartal cardiomyopathy in a young woman].

PMID- 12066556
TI  - [Place for algorithms in the diagnosis of iron-deficiency anemia of gynecologic
      origin in everyday practice].

PMID- 12066557
TI  - Myocardial viability and hibernation: still an incomplete picture.

PMID- 12066558
TI  - Myocardial hibernation.
AB  - Patients with chronic coronary artery disease frequently have contractile
      dysfunction that recovers upon reperfusion. The concept of myocardial hibernation
      views the observed reduction in contractile function not as the result of an
      ongoing energetic deficit, but as an adaptive down-regulation that serves to
      maintain myocardial integrity and viability. In the experiment, perfusion
      contraction matching during the initial hours of ischemia, recovery of energy and
      substrate metabolism during ongoing ischemia, the potential for recruitment of
      inotropic reserve, lack of necrosis, and therefore recovery of function upon
      reperfusion are established features of hibernation. Apart from reduced calcium
      responsiveness, the underlying mechanisms are still unclear. In patients, the
      importance of reduced baseline blood flow vs that of superimposed repetitive
      stunning is somewhat controversial; however, in most studies blood flow is
      reduced, and the myocardium must be ischemic often enough to have persistent
      dysfunction. Morphologically, hibernating myocardium displays features of
      dedifferentiation, with loss of cardiomyocytes and myofibrils, and of
      degeneration, with increased interstitial fibrosis. Patients with hibernating
      myocardium must be identified and undergo revascularization. With a better
      understanding of the underlying mechanisms of hibernation, these adaptive
      responses to ischemia can potentially be recruited and reinforced
      pharmacologically to delay impending myocardial infarction.

PMID- 12066559
TI  - Myocardial hibernation: a noninvasive physician's point of view.
AB  - In a large subset of patients with coronary artery disease and left ventricular
      (LV) dysfunction. LV performance is reduced on the basis of regionally ischemic
      or hibernating myocardium rather than irreversibly infarcted myocardium. The
      detection of reversibly dysfunctional  myocardium is clinically relevant, as
      regional and global LV function in such patients may improve substantially after
      revascularization. Noninvasive imaging methods  to assess myocardial  metabolic
      activity, membrane integrity, and inotropic reserve are ideally suited for this
      assessment. Among these are the  unique potential of nuclear cardiology
      techniques to distinguish viable regions on the basis of perfusion, cell membrane
      integrity, and metabolic activity and the ability of dobutamine echocardiography
      to assess regional inotropic reserve. Contrast-enhanced magnetic resonance
      imaging has also emerged as important method for viability. assessment. Patients
      with LV dysfunction and extensive regions of hibernating myocarduim appear to
      have the potential not only for improved left ventricular function after
      revascularization, but also for improved symptoms and improved survial. This,
      assessing myocardial viability may provide important information regarding the
      selection of patients with LV dysfunction for myocardial revascularization
      procedures.

PMID- 12066560
TI  - Myocardial hibernation: a clinician's perspective.
AB  - Patients with myocardial hibernation have reversible left ventricular dysfunction
      after revascularization. Viability testing can identify those patients whose left
      ventricular dysfunction is primarily due to hibernation rather than scar.
      Patients with a substantial amount of hibernating myocardium seem to have a
      better outcome with revascularization than medical therapy. Patients with poor
      viability do worse after revascularization than patients with good viability.

PMID- 12066561
TI  - Metabolic disorders and cardiovascular risk in HIV-infected patients treated with
      antiretroviral agents.
AB  - The clinical management of HIV-infected individuals is based on highly active
      antiretroviral combination therapy, which provides significant clinical benefit
      in most patients, but causes in a high proportion of them a metabolic syndrome
      that includes body fat redistribution, hypercholesterolemia,
      hypertriglyceridemia, and insulin resistance. These effects are particularly
      evident in patients treated with protease inhibitors. It is likely that the
      metabolic disorders related to anti-HIV treatment will eventually translate into
      an increased cardiovascular risk in patients submitted to such regimens.

PMID- 12066562
TI  - Non-imaging nuclear monitoring of left ventricular function: twenty-five years of
      technical development and clinical experience.
AB  - Although the first non-imaging nuclear probe for clinical application was already
      available 25 years ago, this technique is still underused for the assessment of
      ventricular function. Over the years substantial technological progress rendered
      nuclear probes more accurate and easier to use, and so far the applicability of
      these devices has been evaluated in several experimental and clinical contexts.
      Bedside devices can be used in the evaluation of hemodynamically unstable
      patients and of drug therapy. In patients with several heart diseases,
      particularly with ischemic cardiomyopathy, accurate information on the changes in
      ventricular function occurring during routine activities, as well as during
      structured activities, can be provided using the ambulatory probes. This review
      will focus on the development and clinical application of these diagnostic tools.

PMID- 12066563
TI  - Simultaneous assessment of electrocardiographic parameters for risk
      stratification: validation in healthy subjects.
AB  - BACKGROUND: Sudden cardiac death represents a major public health problem, but in
      the general population the identification of those subjects at very high risk
      remains poor. Simultaneous multiparametric ECG analysis can improve the
      identification of high-risk patients. METHODS: Five-min ECG recordings at a 5 MHz
      sampling rate (extended length-XL-ECG, Mortara Instruments, Milwaukee, WI, USA)
      were acquired in 105 healthy subjects (age range 21 to 80 years), equally
      distributed for age decades and sex, and three additional recordings, 30 min
      apart, were repeated in 30 subjects on the second day. The following parameters
      were recorded and analyzed: the RR interval, QRS duration, QT interval corrected
      according to the Bazett and Fridericia formulae, QT dispersion, T wave
      complexity, activation-recovery interval dispersion, standard deviation of the RR
      intervals, filtered QRS duration, the square root of the mean voltage of the last
      40 ms of the filtered QRS, and the length of time that the terminal vector
      magnitude complex remains < 40 microV. RESULTS: QRS duration, activation-recovery
      interval dispersion, and filtered QRS differed in the two sexes. The standard
      deviation of the RR intervals, T wave complexity and QT dispersion were
      significantly correlated with age. The reproducibility was good for each
      parameter. CONCLUSIONS: The XL-ECG allows the simultaneous calculation of eight
      adequately reproducible different parameters the values of which are in agreement
      with those of the literature. Thus, XL-ECG is a reliable time- and cost-saving
      tool.

PMID- 12066564
TI  - Prevalence and prognosis of atrial septal aneurysm in high risk fetuses without
      structural heart defects.
AB  - BACKGROUND: The aim of this study was to evaluate the prevalence and prognostic
      implications of the association between atrial septal aneurysm (ASA) and fetal
      arrhythmias in a population of high risk fetuses. METHODS: One thousand three
      hundred and two fetal echocardiograms performed during high risk pregnancies from
      the 17th to the 41st week of gestation were retrospectively evaluated for the
      presence of ASA and/or arrhythmias. An ASA was defined as redundant tissue
      extending at least halfway across the left atrium. Patients with an ASA were
      distinguished in two subgroups according to whether there was (subgroup 1) or was
      not (subgroup 2) cyclical contact of the atrial septum with the left atrial wall
      or with the mitral valve. Arrhythmias were documented during mono/two-dimensional
      echocardiography and Doppler evaluation. RESULTS: Out of 1223 patients considered
      for the study, 93 (7.6%) fetuses had an ASA; among these 93 fetuses, 33 (36%) had
      premature atrial beats (p < 0.001). Ten of these patients were included in
      subgroup 1, and 7 of them (70%) exhibited premature atrial beats (p = 0.016 vs
      subgroup 2). No arrhythmias other than premature atrial beats were observed in
      these patients. None of them received any therapy during observation. All of them
      developed a regular sinus rhythm within 3 months of life. CONCLUSIONS: On the
      basis of these data, we can speculate that, if accurately searched for, ASA is
      often present (7.6%) and is likely to represent a mechanical stimulus for the
      generation of premature atrial beats. Indeed, our data show an important
      correlation between the degree of bulging and the presence of arrhythmias,
      supporting the hypothesis of a mechanical stimulus. However, the observed
      arrhythmias did not appear to be prone to degeneration. In conclusion, ASA
      observed during fetal life is often associated with premature atrial beats, which
      are apparently in direct relation with the degree of bulging of the atrial
      septum. On the other hand, an ASA almost invariably disappears at birth and is
      not associated with major arrhythmias.

PMID- 12066565
TI  - Uncomplicated non-Q wave myocardial infarction: long-term prognosis with a
      conservative echo-stress guided management strategy.
AB  - BACKGROUND: Whether an invasive or a conservative strategy should form the basis
      of an optimal management strategy for non-Q wave myocardial infarction is at
      present still subject of debate. We reported our observational experience with
      the long-term follow-up of patients with a first uncomplicated non-Q wave
      myocardial infarction and submitted to a conservative treatment strategy based on
      the in-hospital stress echocardiography and treadmill exercise. METHODS: We
      studied 134 consecutive patients admitted for a first uncomplicated non-Q wave
      myocardial infarction between 1991 and 1994. All patients were submitted to a
      dipyridamole echocardiography test (DET) between 5-7 days after admission and to
      a treadmill test before discharge. Coronary angiography and myocardial
      revascularization (coronary angioplasty or coronary artery bypass grafting) were
      performed according to the outcomes of the stress echo and treadmill test.
      RESULTS: The early and delayed follow-up results were quite good: 2.9% early hard
      events, 15% delayed hard events. DET negativity identified patients with a lower
      risk of both spontaneous and hard events. Multivariate analysis indicated the DET
      as the only predictive variable of spontaneous events within 1 year (p = 0.0001),
      of delayed spontaneous events (p = 0.0001) and of delayed hard events (p = 0.05).
      CONCLUSIONS: In this study, revascularization procedures performed on the basis
      of stress echo result in good short- and long-term outcomes in stabilized
      uncomplicated non-Q wave myocardial infarction. The patients with a negative DET
      had a very low rate of events. DET positivity identifies a higher risk group of
      patients, whatever treatment they subsequently undergo.

PMID- 12066567
TI  - Evidence, at intravenous contrast echocardiography, of coronary arterial supply
      to a metastatic cardiac tumor.

PMID- 12066566
TI  - Scintigraphic results in asymptomatic myocardial infarction patients with
      exercise-induced ST segment elevation.
AB  - BACKGROUND: The mechanism responsible for exercise-induced ST segment elevation
      is debated, but heterogeneous patients were likely included in previous studies.
      This study was specifically aimed at investigating the clinical meaning of
      isolated exercise-induced ST segment elevation in asymptomatic patients with a
      recent acute myocardial infarction (MI). METHODS: We studied 30 patients (28
      males, 2 females, mean age 62 +/- 9 years) with a recent MI who developed ST
      segment elevation in leads with a Q/QS wave pattern, and who did not develop
      angina or ST segment depression during exercise testing and did not have any
      history of post-infarction angina. Patients underwent bicycle 99m-Tc-sestamibi
      (MIBI) myocardial scintigraphy for the assessment of myocardial perfusion and of
      left ventricular function. RESULTS: Only 7 patients (23.3%) showed reversible
      perfusion defects on stress MIBI myocardial scintigraphy, which were mild and of
      limited extension in all. There were no statistically significant differences in
      the main exercise variables between groups with or without stress-related
      perfusion defects. Signs of exercise-related left ventricular dysfunction were
      detected in 6 patients (20%), 3 of whom also showed reversible perfusion defects.
      Again, no significant differences in the main exercise variables were found
      between patients with or without stress-induced scintigraphic abnormalities.
      CONCLUSIONS: In asymptomatic MI patients, isolated exercise-induced ST segment
      elevation in leads with a Q/QS wave pattern is unlikely to represent clinically
      relevant residual myocardial ischemia during exercise, thus suggesting that
      further diagnostic investigations are not necessary in these patients.

PMID- 12066568
TI  - A rare metastatic tumor presenting as outflow obstruction to the right ventricle:
      synovial sarcoma.

PMID- 12066569
TI  - Hydrolysis in pharmaceutical formulations.
AB  - This literature review presents hydrolysis of active pharmaceutical ingredients
      as well as the effects on dosage form stability due to hydrolysis of excipients.
      Mechanisms and measurement methods are discussed and recommendations for
      formulation stabilization are listed.

PMID- 12066570
TI  - Generation of gelatin aerosol particles from nebulized solutions as model drug
      carrier systems.
AB  - PURPOSE: Aerodynamically stable, nebulized aerosols are desirable to achieve
      optimum asthma therapy. Stabilizing droplet size using gel-forming polymers may
      assist in achieving this goal. Semisolid particles may be generated through
      aerosolization of a polymer solution. Gelatin was employed as a model polymer in
      a process optimization study using the marker, disodium fluorescein, and the
      drug, budesonide delivered from two commercially available air-jet nebulizers.
      METHODS: The aerosol delivery system consisted of either of the air-jet
      nebulizers attached to a 30 cm drying column. The nebulizers employed were the
      Aerotech II and Salter SL8900. Two gelatin solutions (0.1 and 0.7% w/v) were
      evaluated following initial density and viscosity measurements. Particle
      characterization was conducted by scanning electron microscopy, eight-stage
      cascade impaction (CI), and phase-Doppler analysis. Disodium fluorescein (NaF, 5
      and 7% w/v) and budesonide (B, 0.05% w/v) were added to the gelatin solutions in
      a 2(4)-factorial design study and the follow-up drug formulation study,
      respectively. The factorial design experiment evaluated the influence of device,
      operating pressure, marker, and gelatin concentrations on mass median aerodynamic
      diameter (MMAD) and fine particle fraction (FPF). Spectrophotometry of the CI
      samples was performed at wavelengths of 486 (NaF) and 254 (B) nm. RESULTS: The
      factorial design experiment utilizing NaF showed that MMADs were not influenced
      significantly be the device, operating pressure, marker, or gelatin
      concentrations (p > 0.05). However, FPFs were significantly influenced by marker
      concentration and device (p < 0.05). In the presence of budesonide, the MMADs and
      FPFs for Aerotech and Salter, respectively, were: MMAD = 1.39 +/- 0.30 microns
      and 1.75 +/- 0.63 microns, FPF = 93.5 +/- 4% and 68.5 +/- 5%, (n = 3). These
      values were consistent with those predicted in the designed experiment.
      CONCLUSIONS: A range of semisolid particle sizes were produced (1.3 < MMAD < 1.8
      microns) for the 0.7% w/v gelatin formulation using different nebulizers. The
      budesonide formulation produced FPFs of 69-93%.

PMID- 12066572
TI  - A novel method for removing residual acetone from gelatin microspheres.
AB  - PURPOSE: To develop a method for removing residual acetone from gelatin
      microspheres. METHODS: Free-flowing gelatin microspheres were either heated under
      vacuum or subjected to a stream of humidified air in a specially designed
      apparatus for removal of the residual acetone. To understand the removal
      mechanism, hygroscopic and thermal properties of the microspheres were examined.
      RESULTS: Heating the gelatin microspheres under vacuum did not reduce the acetone
      level below 2%, but the use of humidified air under fluidizing condition reduced
      the residual acetone in gelatin microspheres by an additional two orders of
      magnitude. The rate of acetone removal was a strong function of the relative
      humidity (RH) of the air stream; higher RH accelerated acetone removal. Other
      variables influencing the acetone removal rate are the mean particle diameter and
      the linear velocity of the humidified air. Under high relative humidities,
      significant amounts of moisture were absorbed into gelatin microspheres, reducing
      their glass transition temperature below 25 degrees C. CONCLUSION: The residual
      acetone in gelatin microspheres can be efficiently removed when exposed to air of
      high RH. Mechanisms of water-dependent acetone removal are proposed.

PMID- 12066571
TI  - The effect of controlled release tablet performance and hydrogel strength on in
      vitro/in vivo correlation.
AB  - The impact of controlled release (CR) formulations having different gel strength
      values (gamma) on in vivo tablet performance and the in vitro/in vivo correlation
      of the formulations was investigated. The CR tablets containing either
      hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer
      were formulated with theophylline and Fast Flo lactose to produce tablets with a
      polymer content of 8 and 30% w/w. gamma was measured using a previously reported
      method. Male beagle dogs were utilized. Results showed that dissolution profiles
      were similar for all three polymers at the same % w/w level of polymer,
      irrespective of media (DI H2O, 0.1 N HCl, and pH 6.8 phosphate buffer). Mean
      gamma values were significantly different (p < or = 0.05) and were in order of
      HPMC K100MP > HPC HXF > carbomer 971P (same 30% w/w) with absolute gamma values
      at 30% w/w in DI H2O of 6600, 4600, and 1600 ergs/cm3, respectively. Drug
      profiles in plasma for the 30% HPMC K100MP tablets were consistent with in vitro
      dissolution profiles and gamma values. Plasma profiles for the 30% HPC HXF
      tablets were similar in vivo as the HPMC tablets. Plasma profiles for the 30%
      carbomer 971P formulation showed much higher drug concentrations (compared to
      HPMC and HPC) in vivo in all dogs. This findings is not consistent with the slow
      drug release found in the dissolution profiles but consistent with its low in
      vitro gamma values. Assessment of the predictability of a level A in vitro/in
      vivo correlation was quantified by absolute mean percent prediction error (PE).
      Formulations having gamma approximately 6000 ergs/cm3 have acceptable PE < 20%,
      and low standard deviation (sigma). Results showed that gamma values of CR
      hydrogel tablets in vitro will affect the in vivo performance (i.e., absorption
      kinetics of the drug) of the tablets and were also found to better assess
      (compared to in vitro dissolution profiles alone) the predictability of in
      vitro/in vivo correlations (level A and multiple level C).

PMID- 12066574
TI  - Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407
      formulation.
AB  - In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb)
      after administration locally at the tumor site, we have developed a thermo
      reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution.
      Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL
      concentrations. The in vitro release studies were carried out in phosphate
      buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407
      formulations were administered intratumorally at a dose of 20 mg/kg in B16F1
      melanoma-bearing mice. The change in tumor volume as a function of time and the
      survival of treated animals were used as measures of efficacy. Poloxamer 407
      solution undergoes a reversible sol-gel transition when the temperature is raised
      to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was
      very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of
      the drug. Significant enhancement in the anti-tumor efficacy was noted following
      intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial
      tumor growth rate was delayed by 67% and the tumor volume doubling time was
      increased by 72% relative to saline control. In addition, more than 91% of the
      tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on
      day 15 post-administration as compared to 58% in the control group. The results
      of this study show significant benefit of paclitaxel for solid tumor when
      administered locally in an in situ gelling poloxamer 407 formulation.

PMID- 12066573
TI  - Investigation of excipient type and level on drug release from controlled release
      tablets containing HPMC.
AB  - The purpose of this study was to investigate the influence of excipient type and
      level on the release of alprazolam formulated in controlled release matrix
      tablets containing hydroxypropyl methylcellulose (HPMC). Each tablet formulation
      contained alprazolam, HPMC (Methocel K4MP), excipients, and magnesium stearate.
      The soluble excipients investigated were lactose monohydrate, sucrose, and
      dextrose, and the insoluble excipients included dicalcium phosphate dihydrate,
      dicalcium phosphate anhydrous, and calcium sulfate dihydrate. The similarity
      factor (f2 factor) was used to compare the dissolution profile of each
      formulation. The insoluble excipients, especially dicalcium phosphate dihydrate,
      caused the drug to be released at a slower rate and to a lesser extent than the
      soluble excipients. Soluble excipients created a more permeable hydrated gel
      layer for drug release, increased the porosity resulting in faster diffusion of
      drug, and increased the rate of tablet erosion. Use of binary mixtures of lactose
      monohydrate and dicalcium phosphate dihydrate produced release profiles of
      intermediate duration. Rapid drug dissolution was obtained when only 9.1% w/w of
      lactose monohydrate was present in the tablet formulation. Only when the
      dicalcium phosphate dihydrate level was sufficiently high (36.5% w/w) was the
      release rate and extent decreased. It was demonstrated that the type and level of
      excipient influenced the rate and extent of drug release from controlled release
      tablets containing HPMC. The release mechanism of alprazolam from each tablet
      formulation was described by either the Hixson-Crowell cube root kinetics
      equation or Peppas's equation. However, the different excipient types
      investigated did not influence the release mechanism of alprazolam from the final
      tablets.

PMID- 12066575
TI  - An adjusted pharmacokinetic equation for predicting drug levels in vivo based on
      in vitro square root of time release kinetics.
AB  - An adjusted pharmacokinetic equation that predicts in vivo plasma drug profiles
      for controlled release (CR) dosage forms having square root of time drug release
      kinetics has been derived. The CR hydrogel tablets containing hydroxypropyl
      methylcellulose (HPMC) were formulated with theophylline and Fast Flo lactose, to
      produce tablets with HPMC K100MP content of 30% w/w. Plasma profiles in vivo were
      determined from four male beagle dogs. Tablet gel strength (gamma) was measured
      as previously reported. Results show drug release in vitro follows square root of
      time kinetics for the formulation in all media (purified H2O, 0.1 N HCl, and pH
      6.8 phosphate buffer). The gamma values were not significantly different (p >
      0.05) among the tablets in different dissolution media, with absolute values in
      DI H2O of 6600 erg/cm3, which is above the minimum threshold value of gamma
      (approximately 6000 erg/cm3) needed for acceptable in vitro/in vivo correlation.
      Comparison of predicted and observed plasma profiles in vivo, using the adjusted
      square root pharmacokinetic equation, showed a better fit of the overall pattern
      and absolute values of the in vivo data as compared to equations that assume
      first- or zero-order drug release from the HPMC based tablets. The adjusted
      square root pharmacokinetic equation can serve as a valuable aid in the design of
      formulations to yield a desired plasma profile in vivo and provides supporting
      evidence to the mechanism of drug release in vitro.

PMID- 12066577
TI  - Use of oxygen scavengers to stabilize solid pharmaceutical dosage forms: a case
      study.
AB  - A case study is described where degradation of a solid pharmaceutical dosage form
      susceptible to oxidation is minimized by incorporation of an oxygen scavenger as
      part of the packaging. Extremely low oxygen levels are attainable within 24 hr of
      packaging, even with permeable high-density polyethylene bottles commonly used in
      the pharmaceutical industry. This packaging methodology allows for a practical
      formulation-independent pathway for reducing or eliminating oxidative
      instability. In addition, this technology provides a convenient mechanistic probe
      for the degradation mechanism of solid dosage forms.

PMID- 12066576
TI  - Significance of respiratory dynamics of the lung tissue in pulmonary drug
      permeation.
AB  - There are two main objectives in this study. One is to investigate the roles of
      respiration, i.e., the dynamic change of the lung tissue, on drug transport
      across the air-blood barrier. The others is to establish the quantitative
      relationship between the effect of respiration and the physicochemical properties
      of drugs. To achieve these objectives, progesterone and a group of its hydroxy
      derivatives with varying hydrophilicity were used as the model drugs and their
      permeation kinetics studies were conducted under simulated respiratory dynamics
      using the in vitro pulmonary permeation system developed earlier in this
      laboratory. The physiological respiratory dynamics were successfully simulated
      and found to enhance significantly the transpulmonary permeation of progesterone
      and its hydroxy derivatives through bullfrog lung membrane, a model air-blood
      barrier. The extent of enhancement in the rate of drug permeation was observed to
      depend on the pattern of pressure application. As a pressure of the same
      magnitude was applied, the respiratory pressure was found to have a greater
      effect than a constant pressure. The results suggested that respiration has
      increased not only the surface area of lung membrane for permeation, but also
      dramatically affected the permeability of the lung membrane. Furthermore, the
      enhancement in permeation rate produced by respiration was observed to be in a
      linear correlation with the hydrophilicity of penetrants. The effect of variation
      in various respiratory parameters on drug permeation was also evaluated, and the
      results suggested that the dynamic change of the lung tissue generated by
      respiration plays an important role in the transpulmonary permeation of drugs. A
      possible mechanism involved could be attributed to the formation of transitional
      pores in lung membrane during the dynamic process of respiration. Therefore, it
      is necessary to bear in mind and take the respiratory dynamics into consideration
      for studying the transpulmonary permeation of drugs, especially when the drug has
      hydrophilic characteristics.

PMID- 12066578
TI  - Modifying the release of gentamicin from microparticles using a PLGA blend.
AB  - Carrier systems for local gentamicin (GS) treatment based on collagen sponges and
      polymethylmethacrylate beads show pharmacokinetic disadvantages in their GS
      release profiles. Therefore, poly(lactic-co-glycolic acid) (PLGA) microparticles
      were devised. None of the five poly(alpha-hydroxy acid)s tested resulted in the
      desired antibiotic release over approximately one week. However, preparing
      microparticles from a 50/50 blend of Resomer RG 502H, an uncapped variety, and
      Resomer RG 503, an endcapped polymer, yielded the targeted liberation profile.
      The mechanism of GS release was investigated by analyzing water uptake and
      polymer molecular weight. Release of GS from RG 502H particles occurred
      instantaneously and coincided with substantial water penetration. Particles
      prepared from RG 503 started out at a higher molecular weight and since the
      endcapped polymer takes up less water, the decrease in molecular weight was
      delayed. The threshold of collapse was reached after two weeks, which coincided
      with water penetration and GS release. For the 50/50 RG 502H/RG 503 blend, this
      process was delayed for two to three days. Hydrolysis occurred at the same rate
      as for RG 502H due to the high water content as a consequence of the uncapped
      polymer fraction and renders GS release over one week with release limited to 30%
      in the first two days due to the endcapped polymer fraction of higher molecular
      weight. Thus, the mixture of endcapped and uncapped Resome exhibits a new quality
      for adjusting drug release from poly(alpha-hydroxy acid)s.

PMID- 12066579
TI  - Anhydrous Carbopol polymer gels for the topical delivery of oxygen/water
      sensitive compounds.
AB  - PURPOSE: The purpose of this study was the development and evaluation of an
      anhydrous glycerin-based Carbopol gel in order to study the stability of the
      oxygen/water-sensitive agent epigallocatechin gallate (EGCG). METHODS: Various
      Carbopol polymers were investigated rheologically at concentrations of 0.25-1%
      using a Brookfield viscometer in order to evaluate their ability to form
      anhydrous glycerin-based formulations. The addition of Transcutol P was evaluated
      in order to create a gel that can be utilized for the incorporation of more
      lipophilic compounds. The suitability of standard neutralizers and their useful
      concentrations were determined to develop guidelines for formulation
      optimization. An accelerated stability study was performed at 50 degrees C to
      evaluate the degradation of EGCG in an anhydrous glycerin gel. RESULTS: It was
      found that Carbopol 974 is the most efficient thickener for anhydrous glycerin
      formulations. In contrast to aqueous gels, anhydrous gels are formed without the
      addition of neutralizers. The rank-order viscosity of the nonneutralized gels
      studied was 974 > 971 > 981 > Pemulen TR-2 approximately 980. The addition of
      neutralizers resulted in a further increase in gel viscosity, with a maximum
      being reached at a concentration of approximately 0.5% w/w. The incorporation of
      Transcutol P resulted in a concentration-dependent loss of gel viscosity. The
      stability data showed that no degradation of EGCG had occurred. CONCLUSION: It
      was shown that anhydrous glycerin-based Carbopol gels can be prepared without the
      need for neutralization. Such vehicles are promising for the incorporation of
      oxygen/water-sensitive drugs.

PMID- 12066580
TI  - Novel metrics to compare dissolution profiles.
AB  - PURPOSE: To evaluate four novel metrics that compare dissolution profiles and
      assess their performance characteristics by comparing dissolution profiles of
      FAST and SLOW immediate release metoprolol tartrate tablets. METHODS: The four
      novel metrics (rho, rho m, delta a, and delta s), along with f2, were applied to
      dissolution data from FAST and SLOW metoprolol tartrate tablets. For example, rho
      m is defined as: [formula: see text] where Rt is the percent dissolved of the
      reference product at time t, Tt the percent dissolved of the test product at time
      t, and RATIOt the larger of either Rt/Tt or Tt/Rt. The mean metric values, upper
      (or lower) confidence limits, and skewness values were calculated, in order to
      characterize the performance of each metric. RESULTS: The mean values of rho, rho
      m, delta a, delta s, and f2 were 1.80, 0.80, 0.47, 0.36, and 19.6, respectively.
      The novel metrics indicate that greater than a 50% relative difference exists
      between the FAST and SLOW profiles. The upper 95% confidence limits for rho, rho
      m, delta a, and delta s were 1.84, 0.83, 0.48, and 0.38, respectively, with f2
      having a lower limit of 19.1. Skewness values for ln-transformed rho, rho m,
      delta a, delta s, and f2 were 0.81, 0.71, 0.86, 0.47, and -0.94, respectively,
      suggesting favorable metric distribution properties. CONCLUSIONS: The direct
      curve comparison metrics rho, rho m, delta a, and delta s appear to be viable
      methods to compare dissolution profiles, particularly rho m.

PMID- 12066581
TI  - Responses of autonomic cardiovascular systems induced by hypoxia: rebound
      phenomenon and species difference.
AB  - The rebound tachycardia, transient increase in heart rate (HR) that was observed
      immediately after the cessation of hypoxia was investigated. Whether the
      cardiovascular responses induced by hypoxia depend on species difference is also
      discussed. Wistar rats were chronically instrumented for measurements of arterial
      blood pressure (ABP), HR and renal sympathetic nerve activity (RSNA), and then
      subjected to hypocapnic (Hypo), isocapnic (Iso) or hypercapnic (Hyper) hypoxia.
      Iso did not affect mean ABP (MAP) or HR, whereas Hypo decreased MAP and increased
      HR, and Hyper increased MAP and decreased HR. RSNA increased in each hypoxia.
      After the cessation of Iso and Hyper, HR transiently increased and then returned
      to that of the control. This HR response did not parallel the changes in RSNA,
      suggesting that "rebound" tachycardia is not due to a sympathetic but rather a
      parasympathetic mechanism. Although it has been generally believed that
      cardiovascular responses to systemic hypoxia depend on the species, there was
      little difference between the results observed in this study and those in
      previous studies under similar experimental conditions. Accordingly, we suggest
      that the cardiovascular responses to systemic hypoxia do not depend on species
      difference but rather on differences in experimental design.

PMID- 12066582
TI  - PVN c-fos expression, HPA axis response and immune cell distribution during
      restraint stress.
AB  - It is well known that stress affects the central nervous system (CNS),
      neuroendocrinoimmune system and other peripheral organs such as the
      gastrointestinal tract. However, the process of adaptation or recovery after
      acute stress reactions in these systems or organs during prolonged stress has not
      yet been adequately investigated. To clarify the process of adaptation or
      recovery in these systems and organs after acute stress reactions, the time
      course of these responses during a single long-duration restraint stress (RTS)
      was studied. The expression of c-fos in the hypothalamic paraventricular nucleus
      (PVN) region of the brain was induced and reached a peak at 0.5 hours for c-fos
      mRNA and 4 hours for c-fos protein (Fos), but disappeared at 2 hours for mRNA and
      16 hours for Fos during continuous RTS. The activation of the hypothalamic
      pituitary-adrenal (HPA) axis during stress resulted in rapid increases in the
      plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT).
      Whereas the increase in ACTH was transient, the rise in CORT was maintained
      throughout the duration of the stress. A rapid significant decrease after stress
      exposure and following a slow and complete or partial recovery were observed in a
      number of total white blood cells (WBC), lymphocytes (LYM), helper T cells (Th)
      and cytotoxic/suppressor T cells (CTL/Ts). A gastric ulcer was found in 1/6 and
      6/6 rats at 8 hours and 16 hours RTS, respectively. These results suggest that
      adaptive changes may occur in c-fos expression in the PVN, ACTH release and
      immune response, but not for CORT release, following acute stress reaction during
      long-duration RTS. In addition, any associated organic damage, such as gastric
      ulceration, was also suggested to possibly be progressive according to the
      duration of RTS.

PMID- 12066583
TI  - Effects of inhaled methyl bromide gas on the metabolic system and kinetics of
      bromine ion in rats.
AB  - Wistar male rats were exposed to 2000 ppm of methyl bromide gas for one hour
      (single exposure experiment) or 300 ppm of the gas for 6 hours a day, 3 days a
      week for 4 or 8 weeks (repeated exposure experiment) to investigate the
      metabolism of inhaled methyl bromide. After the exposure was completed, the
      bromine ion concentration in serum was measured up to 60 days. The serum bromine
      ion concentration was determined by a headspace gas chromatography-mass
      spectrometry after converting bromine ion to methyl bromide by adding dimethyl
      sulfate in the serum samples. In the single exposure experiment, the bromine ion
      concentration decreased quickly within one day after the end of the exposure, and
      then began to decrease gradually. In the repeated exposure experiment, on the
      other hand, the bromine ion concentration decreased almost exponentially. A two
      compartment model was applied to analyze the clearance rate of bromine ion. The
      biological half time of serum bromine ion was 9.1 days for the single exposure
      and 5.4 days for the repeated exposure. The amount of cytochrome P450 (CYP) in
      liver microsomes was measured after the end of exposure. CYP in liver was not
      significantly different after the repeated exposure but it decreased after the
      single exposure.

PMID- 12066584
TI  - Cost-effectiveness of Helicobacter pylori eradication therapy at a company
      occupational health clinic in Japan.
AB  - Peptic ulcer disease (PUD) is a common disorder that follows a chronically
      relapsing course. Many clinical trials have proven the efficacy of H2-blockers in
      the long-term management of chronic relapsing PUD. On the other hand, 30% of
      patients with duodenal ulcer (DU) receiving maintenance therapy with H2-blockers
      experience ulcer recurrence yearly. Helicobacter pylori (H. pylori) is now
      recognized as the major cause of PUD. We estimated the cost-effectiveness of H.
      pylori eradication in comparison to maintenance therapy with H2-blocker in a 1
      year period at a company occupational health clinic. Ninety-nine with PUD tested
      for H. pylori were positive. Forty-nine patients received H. pylori eradication,
      and the remaining 50 patients were treated with ranitidine (RAN) 150 mg for 1
      year according to their demands. H. pylori was successfully eradicated in 42
      patients (86%), and 41 (98%) of these 42 patients remained free of symptoms for
      the remainder of the study period. The lifetable probability of ulcer recurrence
      during 1 year was significantly lower for patients who received eradication
      (6.1%) compared with those who received RAN alone (24.0%). The total cost for H.
      pylori eradication was lower than that for maintenance therapy along our study
      design (102,664 yen vs 150,356 yen). A decision tree was illustrated and the
      total cost were calculated by using sensitivity analysis. When we used baseline
      probabilities in sensitivity analysis, the total cost for eradication was lower
      than that for maintenance therapy (104,647 yen vs 154,468 yen). H. pylori
      eradication is cost-effective therapy for patients with PUD in comparison to
      maintenance therapy with RAN at an on-site occupational health clinic in Japan.

PMID- 12066586
TI  - [Pulmonary resection for metastatic colorectal cancer].
AB  - We analyzed the outcome of 30 patients who underwent surgery (40 operations) for
      pulmonary metastases of colorectal cancer. Overall 5-year survival rate was 56%.
      There were no significant differences in survivals 5 years after the first
      surgery on the basis of potential prognostic factors: disease free interval,
      number of pulmonary metastases and size of metastatic lesion. Three patients with
      recurrent pulmonary metastases after the first resection underwent repeated
      resections and are alive 23, 58 and 62 months after the first pulmonary
      metastasectomy, respectively. Pulmonary resection for metastases from colorectal
      cancer prolonged the survival of patients, even those with bilateral lesions or
      recurrent metastases. These results confirm that pulmonary resection for
      metastatic colorectal cancer is a potentially curative therapy.

PMID- 12066587
TI  - [Occupational safety and health at small scale enterprises co-operating with a
      medical university].
AB  - This descriptive study reports the results of a systematic survey on occupational
      safety and health hazards and risks to exposed workers at companies co-operating
      with a medical university, and investigates the effective methods for their
      management. Varieties of works at all these co-operating companies have been
      categorized into 14 types of businesses. The survey was performed in two-fold; an
      individual interview of managers and a comprehensive inspection of workshops, and
      a questionnaire to all workers (response rate 95.9%). All of the co-operating
      companies were small-scale enterprises with less than 50 employees. The
      occupational safety and health risks to be controlled were accidental contact
      with biomedical wastes, heat in the kitchen, laundry and boiler room, unfavorable
      ventilation at workplace close to medical facility, and physical fatigue of
      guards and janitors. A higher number of occupational health physicians and a
      higher rate of health examinations were observed compared to other small-scale
      enterprises in Japan. About 80% of all workers were conscious of working on the
      premises of medical facilities. To improve the occupational safety and health
      activities of co-operating companies, we propose the use of professionals at the
      medical university, the promotion of joint activities among the co-operating
      companies, and the strengthening of mutual connection and coordination between
      the co-operating companies and the medical university.

PMID- 12066588
TI  - [Function of clara cells in lung remodeling].
AB  - Clara cells localized in the bronchiole are thought to play a key role in lung
      remodeling. Clara cell secretory protein (CCSP), which is specifically produced
      by Clara cells, inhibits pro-inflammatory cytokines and chemotaxis of
      fibroblasts, and acts as phospholopase A2 inhibitors, and may also inhibit
      inflammation and fibrosis in the lung. This could be a biomarker of interstitial
      pneumonitis. Proliferation of Clara cells and neuroendocrine cells at airway
      epithelial injury may act as progenitor cells during the repair process.

PMID- 12066589
TI  - [Sporotrichosis in farmers].
AB  - Eleven cases of sporotrichosis treated in our clinic were statically evaluated
      and two cases suffered by farmers are presented. In urban areas, because of the
      great popularity of gardening, patients with sporotrichosis are increasing among
      gardeners. Because sporotrichosis is an occupational skin disease, enlightenment
      of farmers and gardeners regarding the importance of prevention of skin injury as
      a route to infection during farm work or gardening is necessary. In addition,
      dermatologists have to spread information regarding the fungal infections to the
      public.

PMID- 12066591
TI  - Public health law: a renaissance.

PMID- 12066590
TI  - [Two cases of synchronous superficial double cancers in the esophagus and
      stomach].
AB  - Two surgical cases of synchronous double esophageal and gastric cancer, both of
      which revealed a superficial type were investigated. The first case was a 58
      years old man, who was found to have an abnormal gastric shadow on mass
      screening. Gastrointestinal examination revealed a synchronous double cancer of
      the esophagus (Mt-Lt, m) and stomach (L, m). An endoscopic mucosal resection was
      performed on the gastric cancer and after 3 weeks a blunt dissection on the
      esophageal cancer was performed and the gastric tube was reconstructed. The
      second case was a 65 years old man, who was found to have an ulcerative
      esophageal tumor (Ut, type 2) and a gastric tumor (M, 0-II c) at the anterior
      wall of the upper body on gastrointestinal examination for a complaint of
      hematemesis. A subtotal esophagectomy and a lymph node dissection was performed
      in which reconstruction was made by using a gastric tube avoiding the gastric
      cancer lesion. We also reviewed previous reports of 22 cases that had synchronous
      superficial esophageal and gastric cancer, and discussed the indications and
      methods of operation.

PMID- 12066592
TI  - Public health legal preparedness for the 21st century.

PMID- 12066593
TI  - Rethinking the meaning of public health.

PMID- 12066594
TI  - A globalized theory of public health law.

PMID- 12066595
TI  - Public health ethics: mapping the terrain.

PMID- 12066596
TI  - Disease stigma in U.S. public health law.

PMID- 12066597
TI  - Managed care and public health: conflict and collaboration.

PMID- 12066598
TI  - After September 11: rethinking public health federalism.

PMID- 12066599
TI  - Administrative law and the public's health.

PMID- 12066600
TI  - Litigation as public health policy: theory or reality?

PMID- 12066601
TI  - Evaluating the impact of criminal laws on HIV risk behavior.

PMID- 12066602
TI  - Bioterrorism law and policy: critical choices in public health.

PMID- 12066603
TI  - Critical biological agents: disease reporting as a tool for determining
      bioterrorism preparedness.

PMID- 12066604
TI  - Injury as a field of public health: achievements and controversies.

PMID- 12066605
TI  - Regulating tobacco: the need for a public health judicial decision-making canon.

PMID- 12066606
TI  - The complex relationship of genetics, groups, and health: what it means for
      public health.

PMID- 12066607
TI  - Other branches of science are necessary to form a lawyer: teaching public health
      law in law school.

PMID- 12066608
TI  - A rightful place for public health in American law.

PMID- 12066610
TI  - HIPAA compliance: lessons from the repeal of Hawaii's patient privacy law.

PMID- 12066609
TI  - Conflicts of interest in clinical research: addressing the issue of physician
      remuneration.

PMID- 12066611
TI  - Health care: mandatory nurse-to-patient staffing ratios in California.

PMID- 12066612
TI  - Duty of care: no higher standard of tort liability for incapacitated patients.

PMID- 12066613
TI  - Consumer protection: online sale of prescription drugs to minors not
      unconscionable.

PMID- 12066614
TI  - Intellectual property: plants patentable under the Utility Patent Statute, PVA,
      and PVPA.

PMID- 12066615
TI  - False Claims Act: failure to seek legal advice not a violation of the FCA.

PMID- 12066618
TI  - The Model State Emergency Health Powers Act. As of December 21, 2001.

PMID- 12066616
TI  - Patient confidentiality: hospital's release of alcohol treatment data does not
      violate regs.

PMID- 12066619
TI  - Overview of the Partnership Symposium 2001: patient safety--stories of success.

PMID- 12066620
TI  - Developing a systemwide approach to patient safety: the first year.
AB  - BACKGROUND: Health care organizations face an imperative to ensure that care is
      provided to patients in the safest manner possible. In 2000 INTEGRIS Health, an
      Oklahoma City-based health system including ten acute care organizations,
      developed a patient safety framework that was built on the foundation of a
      culture of patient safety and began implementation in January 2001. IMPORTANCE OF
      LEADERSHIP IN PATIENT SAFETY: The first step in establishing a culture of safety
      was to ensure that leadership and the entire organization understand the
      rationale for a focus on patient safety. The traditional blaming approach will
      not prevent human error; staff need to speak freely, to talk about errors that
      happen and those that almost happen, and to identify where mistakes are likely
      and where systems allow mistakes to get through. Systems and processes should
      make it difficult for staff to make mistakes and easy for them to do things
      correctly. EXPERIENCE TO DATE: Since our efforts began, staff have helped
      identify multiple accidents waiting to happen. For example, an anesthesiologist,
      the service chief at one of our large hospitals, prepared a list of safety issues
      immediately after hearing a presentation to the Medical Executive Committee. Many
      system flaws have been identified as a result of our discussions; some of the
      solutions are easy and some much more complex. CHALLENGES: Challenges include
      keeping patient safety highly visible and demonstrating progress in our
      implementation, developing effective mechanisms for communicating safety
      solutions and ensuring that they are implemented in all the facilities, and
      figuring out how to measure success in a meaningful way.

PMID- 12066621
TI  - The Safety Case Management Committee: expanding the avenues for addressing
      patient safety.
AB  - BACKGROUND: The greatest gains in patient safety are likely to result from using
      a multifaceted framework of safety enhancement initiatives. The Safety Case
      Management Committee, which has been meeting at the VA Ann Arbor Healthcare
      System since early 1999, is one such initiative; it is directed at broadening
      organizational involvement in creating a safer clinical environment. The
      committee's objective is to address fundamental issues related to patient safety
      and quality of care. The committee aims to develop thematic approaches to
      improving major systems triggered by unsafe or risky incidents that demonstrate
      either iatrogenic harm or risk of harm to patients. COMMITTEE STRUCTURE AND
      FUNCTIONING: Committee members represent top management, middle management, and
      front-line employees, but membership is weighted toward those in direct patient
      care roles. The group also includes a consumer representative. Critical issues
      are addressed through rigorous case discussion, literature review, and expert
      consultation. RESULTS: In a 3-year period (Feb 1999 through Dec 2001), 85% of the
      group's 45 recommendations have been implemented. Topics have included reducing
      medication errors during emergency procedures, enhancing palliative care
      services, minimizing the risk of missed x-ray findings, optimizing
      anticoagulation management, reducing the risk of vascular catheter-related
      infection, and improving pain management. SUMMARY: The Safety Case Management
      Committee has successfully addressed actual and potential errors and has
      implemented strategic safety improvements. The dedicated efforts of highly
      motivated clinicians who serve on such a committee can augment and enhance risk
      management advances made through other channels.

PMID- 12066622
TI  - The safety checklist program: creating a culture of safety in intensive care
      units.
AB  - BACKGROUND: In 1999 the VA Ann Arbor Healthcare System began a safety checklist
      program to help build a culture of safety among nurses, respiratory therapists,
      and unit maintenance providers in the intensive care units (ICUs). Program
      objectives were to (a) create the opportunity for each participating staff member
      to view his or her work and unit environment in a broader safety context; (b)
      establish clear, concise, and measurable standards that staff would identify and
      value as important safety factors; (c) develop a data collection methodology that
      would minimize confirmation bias; and (d) correct safety deficits immediately.
      DATA MANAGEMENT: Staff measure compliance with safety standards twice daily and
      record results on a form specifically designed for the project. Data are
      transferred to a spreadsheet, and graphic presentations are posted in each ICU.
      Staff periodically adjust both standards and data collection procedures. SUMMARY:
      Staff can articulate how the program is making the ICU a safer environment.
      Nursing response to a recent major error reflects the growth that has occurred
      since the program's inception. Safety checks performed by ICU staff are critical
      in maintaining a constant level of safety. Although the effect on untoward events
      was not measured, the potential for incidents, including medication and
      intravenous errors, nosocomial infections, ventilator complications, and
      restraint complications may be reduced. The program invests bedside clinicians in
      writing safety standards, creates a partnership between staff and the clinical
      risk manager, and provides executive leaders an opportunity to demonstrate
      support of a culture beyond blame.

PMID- 12066623
TI  - A qualitative analysis of medication use variance reports.
AB  - BACKGROUND: This report of a process change utilized a qualitative approach to
      data analysis to improve medication use safety in a large hospital. The two goals
      were to design a strategy to analyze the qualitative data and to use that
      strategy to uncover previously unclassified medication use variance patterns that
      could be prevented. A multidisciplinary team performed the analysis in an effort
      to improve the quality and yield of the approach. METHODS: All medication use
      variance, incident, and event reports from Yale-New Haven Hospital during April
      June 2000 were collected (N = 264). A 20% random sample of the reports was
      distributed to a five-member evaluation group (a pharmacist, two nurses, and two
      physicians) for independent qualitative analysis and coding. An initial coding
      framework was produced using a consensus process. This coding framework was
      applied to another sample, and the consensus and coding processes were repeated
      until no new domains were identified. RESULTS: Ten general medication use
      variance domains were determined. In addition, 21 subdomains among the various
      general domains were determined. DISCUSSION: Utilizing a multidisciplinary team
      and a qualitative strategy of analysis improved patient safety efforts. This
      combination led to the discovery of new variance domains, causes, and
      opportunities to intervene and ultimately prevent medication use variances. This
      analytic approach is widely applicable, adaptable, and dynamic. The design and
      results of this report improve on a strictly quantitative approach to medication
      use variance analysis. The approach employed by this report will be used to
      improve medication use safety within the Yale-New Haven Health System.

PMID- 12066624
TI  - Transformation of a pharmacy department: impact on pharmacist interventions,
      error prevention, and cost.
AB  - BACKGROUND: Current medical literature supports the unit-based (UB) pharmacy
      concept as a best practice. In an effort to determine its feasibility, Huntsville
      Hospital (Huntsville, Alabama) conducted a pilot study to compare the central
      based (CB) model with the UB model and then implemented the new model.
      IMPLEMENTING THE PILOT STUDY: Data were collected for two high-volume nursing
      units for 10 days for each model. Pharmacists practicing in the UB setting
      documented more interventions than the CB pharmacist by a factor of three to one,
      resulting in an 85% increase in cost avoidance. IMPLEMENTING THE UB MODEL:
      Converting the pharmacy services to a UB model entailed creating 16 new
      pharmacist positions. Extrapolation of the savings for the UB model ($520 per
      day) and the CB model ($280) for 1 year suggested that adoption of the UB model
      would generate an additional $87,600 in cost avoidance for these two nursing
      units. Each new pharmacist was trained for at least 3 months before being
      scheduled to work independently as a UB pharmacist. Clinical interventions by
      pharmacists greatly increased after implementation of the UB model. The baseline
      monthly average of interventions for the 6 months before implementation was 239,
      and the monthly cost avoidance was $21,300. In October 2001, the first full month
      of implementation, there were 1,315 interventions and a monthly cost avoidance of
      $130,192. SUMMARY: Converting to the UB model has required a considerable
      increase in the number of pharmacist positions, yet there has been a dramatic
      increase in clinical pharmacy interventions, with a corresponding decrease in
      drug expenditures.

PMID- 12066625
TI  - Failure mode and effect analysis: an application in reducing risk in blood
      transfusion.
AB  - BACKGROUND: In February 2001 Good Samaritan Hospital in Dayton, Ohio, conducted a
      Failure Mode and Effect Analysis (FMEA) on the blood transfusion process to
      reduce the risk of problems inherent in the procedure. DEVELOPING THE FMEA: The
      major steps of the analysis were to identify problems (failure modes), define
      their causes, and surmise the effects if failures occurred. Numerical scores were
      assigned for the likelihood of failure occurrence, the severity of the effects,
      and the possibility that the failure would escape detection. These scores were
      multiplied and reported as a risk priority number (RPN) for each failure mode.
      Solutions (process redesign actions) and monitoring plans (design validation)
      were developed to address the failure modes with the highest RPNs. PRESENTING THE
      FMEA: In March 2001 the FMEA document was presented to the Safety Board, which
      approved design changes such as use of a blood barrier system that restricts
      access to the blood until a patient-specific code is dialed. RESULTS: Measures
      were developed to analyze results, and rapid-cycle Plan-Do-Study-Act methodology
      was used to test and document redesign changes; most became the standard
      operating procedure. The new process accomplished its purpose of preventing
      serious, avoidable errors. No outcome errors occurred from March 2001 through
      June 2001 or in the 8 months following housewide implementation on June 18, 2001.
      DISCUSSION: FMEA was a valuable tool in error-trapping the blood transfusion
      process. Yet the FMEA process was time-consuming, tedious, and difficult and
      should be reserved for an organization's highest-priority processes.

PMID- 12066626
TI  - A Web-based program for implementing evidence-based patient safety
      recommendations.
AB  - BACKGROUND: In response to increasing national concerns about medical safety,
      product developers from a health services research and software group recently
      created a commercial Web-based program to address a wide variety of patient
      safety issues in the acute care setting. They also wanted to provide a program
      with credible, referenced, and up-to-date content, not just a technology
      infrastructure for reporting errors. SAFETY OPTIMIZER: This Web-based program,
      which has evolved over time, now features seven modules for assessing
      organizational risk and for implementing strategies to reduce risk. The
      Literature Module features detailed synopses that are graded and organized into
      summary statements to provide recommendations for improving patient safety. The
      Implementation/Tracking Module includes numerous risk-reduction strategies. The
      Incident Reporting Module enables the collection of data at the point of care on
      a variety of incidents, using either paper-based or on-line forms. Other modules
      offer opportunities to assess adherence to JCAHO patient safety standards,
      forecast the benefits of certain evidence-based guidelines, evaluate staff
      competency, and obtain information from a variety of key safety Web sites.
      EXPERIENCE TO DATE: The program is in use at more than 30 health care
      organization facilities and systems. It is still too early to provide
      quantitative data on the impact of this program on patient safety. CONCLUSIONS:
      It is hoped that vendor solutions such as the one described in this article will
      help organizations develop a practical and effective framework for addressing the
      wide range of issues in patient safety.

PMID- 12066628
TI  - Hey, doc, I still have a lot of living to do.

PMID- 12066627
TI  - Using administrative data to improve compliance with mandatory state event
      reporting.
AB  - BACKGROUND: The New York Patient Occurrence and Tracking System (NYPORTS) is a
      mandatory adverse event reporting system that was redesigned in 1998. Analysis of
      the first full year of its use showed large regional and hospital variation in
      reporting frequency not due to hospital or case mix differences. In early 2001,
      New York State mandated that all hospitals conduct retrospective review for
      unreported adverse incidents for the previous 2 years. Hospitals could submit
      previously unreported incidents within a defined window without penalty. The
      hospital used an ICD-9-CM (International Classification of Diseases, Ninth
      Revision, Clinical Modification) analysis to screen for missed NYPORTS cases, to
      assist in focusing review resources. METHODS: NYPORTS categories were matched to
      corresponding combinations of inpatient ICD-9-CM diagnosis and procedure codes.
      Other variables considered included discharge disposition, primary or secondary
      coding position, readmissions, and NYPORTS exclusions. RESULTS: Among more than
      60,000 discharges in 2 years, 5,500 records were identified for NYPORTS review
      based on the ICD-9-CM criteria; 211 cases had already been reported through
      normal reporting processes. Thirteen of the NYPORTS codes had a 30% or greater
      match rate to the ICD-9-CM codes, with an average "hit rate" of 56%. Five-hundred
      sixty reviews identified 187 (33.4%) reportable events for the same code the case
      was being screened for and 26 additional reportable events for a code other than
      the screening code. NYPORTS categories for procedure and operative-related
      occurrences had the highest yields. CONCLUSIONS: This retrospective effort helped
      identify previously unreported occurrences, increase institutional awareness of
      New York State's mandatory reporting process, and stimulate the redesign of our
      concurrent detection process.

PMID- 12066629
TI  - The diet of last resort.

PMID- 12066630
TI  - Fighting G-force.

PMID- 12066631
TI  - Prosthodontics, a specialty at a crossroads since its inception.

PMID- 12066632
TI  - Stress analysis of metal-free polymer crowns using the three-dimensional finite
      element method.
AB  - PURPOSE: The purpose of this study was to evaluate the stress distribution under
      various loading conditions within posterior metal-free crowns made of new
      composite materials. MATERIALS AND METHODS: A three-dimensional finite element
      model representing a mandibular first molar was constructed. Variations of the
      model had crowns of two types of composite, a glass ceramic, and porcelain fused
      to metal. A load of 600 N, simulating the maximum bite force, was applied
      vertically to the crowns. Loads of 225 N, simulating masticatory force, were
      applied from three directions (vertically, at a 45-degree angle, and
      horizontally). RESULTS: The stress distributions in both types of composite crown
      were similar to that of the glass-ceramic crown. In the test simulating maximum
      bite force, the maximum tensile stresses on all crowns (17.9 to 18.3 MPa)
      concentrated around the loading points. In the masticatory force-stimulation
      test, the specimens experienced maximum tensile stresses of 20.3 to 26.6 MPa
      under a horizontal load and 10.9 to 11.0 MPa under a vertical load. When the load
      was applied horizontally, the maximum tensile stress was observed around the
      loading points on the surface in the case of composite and glass-ceramic crowns,
      and in the cervical area of the metal coping in the porcelain-fused-to-metal
      crowns. CONCLUSION: It would appear that the strength of occlusal contact points
      is important to the integrity of posterior metal-free crowns made of new
      composite materials and that bite forces applied from the horizontal direction
      are a critical factor determining success and failure.

PMID- 12066633
TI  - Stress distribution on the metal framework of the implant-supported fixed
      prosthesis using different veneering materials.
AB  - PURPOSE: This study evaluated stress distribution in metal frameworks constructed
      on implants under masticatory forces using computer simulations. MATERIALS AND
      METHODS: Three-dimensional finite element analysis was used to study four
      different veneering materials-metal framework combinations using Calcitek
      implants. The veneering materials used in the study were porcelain, heat
      polymerized poly(methyl methacrylate) resin, microfilled composite resin, and
      glass-modified composite resin. All computations were conducted for different
      levels on the buccal and lingual sides. RESULTS: Changing the veneering material
      on the prosthesis produced significant effects on stress levels and stress
      distribution on the metal frameworks. Stresses were concentrated along the
      marginal area of the prosthesis. Acrylic resin showed greater displacement than
      porcelain, probably because of its lower modulus of elasticity. CONCLUSION: In
      comparison to porcelain, more stress is borne by the acrylic resin-veneered metal
      framework under static loading.

PMID- 12066634
TI  - Effect of seating force, margin design, and cement on marginal seal and retention
      of complete metal crowns.
AB  - PURPOSE: The purpose of this study was to determine the marginal discrepancy and
      retention of silver-palladium crowns cemented with zinc phosphate (Phosphacap)
      and glass-ionomer cement (Fuji Cap 1) using different seating forces on
      preparations with various margin designs. MATERIALS AND METHODS: Crown
      preparations with three finish lines--chamfer, shoulder, and shoulder with a 45
      degree bevel--were sequentially prepared on a dentoform premolar. A metal die for
      each of the three finish lines was constructed. Complete metal crowns were
      fabricated for each metal die using a silver-palladium alloy. Three different
      seating forces--25, 100, and 300 N--were used to load the crowns until initial
      set of the cement. The marginal discrepancy was calculated by measuring the
      change in crown height before and after cementation using a digimatic indicator.
      Retention was determined by measuring the tensile strength using the Lloyd
      universal testing machine. RESULTS: The higher seating forces produced better
      crown seating but had no significant effect on crown retention. The shoulder and
      shoulder with bevel finish lines provided better crown retention than the
      chamfer. Glass-ionomer cement provided greater crown retention than zinc
      phosphate cement. No significant correlation between marginal seating and crown
      retention was revealed using a Pearson analysis. CONCLUSION: Marginal seal was
      not influenced by either margin design or type of luting cement, but was improved
      with higher seating force. Crown retention was affected by the margin finish line
      and the luting agent.

PMID- 12066635
TI  - Long-term prosthodontic follow-up and revisional treatment of patients with cleft
      lip and palate: case presentation.
AB  - PURPOSE: The purpose of this article is to draw attention to the need for regular
      life-long follow-up care of cleft lip and palate patients to maintain adequate
      masticatory function, speech, and esthetics, thereby supporting psychosocial
      function. MATERIALS AND METHODS: Initial and revisional prosthodontic treatments
      over a period of 32 years in a patient with a bilateral cleft lip and palate are
      described. RESULTS: Despite an initial dentition of poor health and prognosis and
      suboptimal patient cooperation, it was possible to arrive at an improved clinical
      and radiologic state of oral health by the end of the observation period.
      CONCLUSION: Regular life-long prosthodontic follow-up with adequate maintenance
      and revisional treatments should be regarded as an essential part of the long
      term care for subjects with clefts.

PMID- 12066636
TI  - Treatment outcomes with removable partial dentures: a comparison between patient
      and prosthodontist assessments.
AB  - PURPOSE: This article presents the results from a survey of patients' degree of
      satisfaction with their removable partial dentures (RPD) and the comparison
      between patient and prosthodontist assessments. MATERIALS AND METHODS: A total of
      165 experienced RPD wearers filled in a questionnaire and graded their RPDs
      depending on their level of satisfaction. A scale ranging from 1 to 5 was used to
      assess general satisfaction with RPDs and to assess their esthetics, retention,
      and hygiene. A specialist in prosthodontics assessed the same prostheses using
      the same scale, not knowing the patient's opinion. RESULTS: The patients'
      assessments were high, and more than half of them graded their dentures as
      excellent. On average, all variables were assessed higher by the patients than by
      the prosthodontist (P < .001). For the patients who gave the worst grades to
      their dentures, the grades were lower than the prosthodontist's (P < .001), while
      the satisfied patients graded their dentures much better than did the
      prosthodontist (P < .001). CONCLUSION: On average, patient assessment of the
      treatment outcomes with RPDs was less critical than prosthodontist assessment.
      However, the few dissatisfied patients assessed their dentures worse than did the
      prosthodontist.

PMID- 12066637
TI  - Interchangeability of a semiadjustable articulator.
AB  - PURPOSE: The purpose of this study was to investigate whether the
      interchangeability of new Hanau semiadjustable articulators fulfills the
      manufacturer's criterion (102 microns) in the mediolateral direction and the
      defined 166-micron criterion three dimensionally and whether the articulators
      maintain the same interchangeability as new articulators after a period of
      function. MATERIALS AND METHODS: The spatial deviations in three dimensions of
      ten new, ten 18-month-old, and ten 30-month-old Hanau articulators were measured
      with a field-inspection gauge and compared to those of a master articulator.
      RESULTS: Compared to the master articulator, nine of 10 new articulators met the
      manufacturer's criterion of articulator interchangeability in the mediolateral
      direction. However, only four of the 10 articulators fulfilled the criterion for
      three-dimensional interchangeability. The articulators were found to be
      interchangeable among the groups when the spatial deviations of test articulators
      from the master articulator at the position of the lingual cusp of the right
      maxillary first premolar were compared. However, using the geometric mean
      deviations of test articulators, the 30-month group was not interchangeable with
      the new and the 18-month articulator groups. CONCLUSION: This limited study
      revealed that most of the articulators tested met the manufacturer's criterion of
      articulator interchangeability, but most did not pass the three-dimensional
      interchangeability test. Clinicians should be aware of the amount of occlusal
      error in the range of 0.2 mm that may result from interchanging dental casts on
      the articulator system. The articulator system might be able to maintain the same
      level of interchangeability for up to 18 months of routine use.

PMID- 12066638
TI  - Alumina ceramic implant abutments used for single-tooth replacement: a
      prospective 1- to 3-year multicenter study.
AB  - PURPOSE: The aim of the study was to compare results after 1 and 3 years when
      single crowns supported by CerAdapt (test) ceramic abutments or CeraOne (control)
      titanium abutments were loaded. MATERIALS AND METHODS: The material was divided
      into two groups: in group A, 69 (34 test, 35 control) abutments/crowns from all
      involved clinics were followed for 1 year; and in group B, 20 (10 test, 10
      control) abutments/crowns from one of the clinics were followed for 3 years.
      RESULTS: No implant failed, giving a cumulative success rate of 100% for the
      implants. Two CerAdapt abutments in group A fractured, giving a cumulative
      success rate of 93% for the CerAdapt and 100% for the CeraOne abutments after 1
      year. No abutment failed in group B, giving a cumulative success rate of 100%
      both for the CerAdapt and the CeraOne abutments between 1 and 3 years. The
      CerAdapt fractures might have been due to the fact that the abutments were
      impaired through too-extensive preparation and/or had been exposed to a too-high
      bending moment. Almost no marginal bone loss was recorded, indicating a stable
      bone situation both at CerAdapt and CeraOne abutments on single-tooth implants.
      Healthy conditions, with a relatively stable level of the periimplant mucosa in
      relation to the abutment/crown, were recorded for soft tissues both at CerAdapt
      and CeraOne abutments. Both clinicians and patients rated the esthetic result as
      excellent for practically all cases. CONCLUSION: The results demonstrate the
      esthetic possibilities and the safety of single-tooth replacement when accepted
      treatment concepts are followed and documented components are used. The tested
      abutments worked well, although the fractured CerAdapt abutments indicate that
      ceramic abutments are more sensitive to handling procedures than the titanium
      abutments.

PMID- 12066639
TI  - Cytotoxic effects of denture base materials on a permanent human oral epithelial
      cell line and on primary human oral fibroblasts in vitro.
AB  - PURPOSE: The objective of this study was to determine the cytocompatibility of
      three different extracts of denture base resins and to compare the cytotoxic
      effect of these materials on a human oral epithelial KB cell line and primary
      human oral fibroblasts derived from buccal mucosa. MATERIALS AND METHODS: Set
      specimens from a heat-cured resin, a self-cured resin, and a light-cured resin
      were eluted with culture medium for 1, 3, and 5 days. Cytotoxicity was judged
      using tetrazolium bromide reduction assay. RESULTS: The eluates from self-cured,
      heat-cured, and light-cured denture base resins were cytotoxic to primary human
      buccal fibroblast cultures and KB cells. Self-cured resin was the most toxic
      denture base material among the chemicals tested in all cultures. The
      cytotoxicity decreased in the order of self-cured resin > heat-cured resin >
      light-cured resin for KB cells. The rank for buccal fibroblast cells was self
      cured resin > heat-cured resin > light-cured resin. CONCLUSION: The influence of
      the cytotoxicity depended on the materials tested and the cell culture system
      used. The use of both permanent and primary cells is recommended for a better
      screening of the cytotoxic effects of denture base resins.

PMID- 12066640
TI  - Effect of occlusal wear on bone loss and Periotest value of dental implants.
AB  - PURPOSE: Occlusal overload may contribute to the loss of osseointegration of oral
      implants, so some clinicians are reluctant to place implants in patients with
      signs of bruxism. This study evaluated the effect of occlusal wear as a probable
      sign of bruxism on bone loss and implant stability. MATERIALS AND METHODS: The
      study investigated 379 patients who had worn implant-retained or implant
      supported restorations for many years. Occlusal wear, patient age and gender,
      time of prosthetic loading, jaw, location in the dental arch, implant diameter,
      prosthesis construction, occlusal material, periimplantitis, and loosening of the
      prosthetic construction were recorded. One implant from each patient was selected
      for radiographic and Periotest measurements. The implant with the highest bone
      resorption was chosen. A forward stepwise multiple linear regression analysis was
      performed to analyze the effect of the explanatory variables on Periotest value
      and radiographic bone loss. RESULTS: The statistical models could account for
      part of the variation in bone loss rate and Periotest value. Some influence of
      time of loading, jaw, and implant diameter on bone loss or Periotest value was
      formally established. Occlusal wear failed to have any statistical impact on
      vertical annual bone loss rate or Periotest value. CONCLUSION: This study gave no
      indication that implants in patients with occlusal wear have an increased bone
      loss rate or Periotest value.

PMID- 12066641
TI  - Adhesion of resin composite core materials to dentin.
AB  - PURPOSE: This study determined (1) the effect of polymerization mode of resin
      composite core materials and dental adhesives on the bond strength to dentin, and
      (2) if dental adhesives perform as well to dentin etched with phosphoric acid as
      to dentin etched with self-etching primer. MATERIALS AND METHODS: Human third
      molars were sectioned 2 mm from the highest pulp horn and polished. Three core
      materials (Fluorocore [dual cured], Core Paste [self-cured], and Clearfil Photo
      Core [light cured]) and two adhesives (Prime & Bond NT Dual Cure and Clearfil SE
      Bond [light cured]) were bonded to dentin using two dentin etching conditions.
      After storage, specimens were debonded in microtension and bond strengths were
      calculated. Scanning electron micrographs of representative bonding interfaces
      were analyzed. RESULTS: Analysis showed differences among core materials,
      adhesives, and etching conditions. Among core materials, dual-cured Fluorocore
      had the highest bond strengths. There were incompatibilities between self-cured
      Core Paste and Prime & Bond NT in both etched (0 MPa) and nonetched (3.0 MPa)
      dentin. Among adhesives, in most cases Clearfil SE Bond had higher bond strengths
      than Prime & Bond NT and bond strengths were higher to self-etched than to
      phosphoric acid-etched dentin. Scanning electron micrographs did not show a
      relationship between resin tags and bond strengths. CONCLUSION: There were
      incompatibilities between a self-cured core material and a dual-cured adhesive.
      All other combinations of core materials and adhesives produced strong in vitro
      bond strengths both in the self-etched and phosphoric acid-etched conditions.

PMID- 12066642
TI  - Adherence of Candida species to newly polymerized and water-stored denture base
      polymers.
AB  - PURPOSE: The aim of this in vitro study was to examine the adherence of yeasts to
      newly polymerized and water-stored denture base polymers using four Candida
      strains with different cell surface hydrophobicities. MATERIALS AND METHODS:
      Thirty-two autopolymerized denture base polymer specimens were stored in
      distilled water at 37 degrees C for 7 days and 32 were newly polymerized. Sixteen
      specimens of each group were pretreated with unstimulated mixed saliva (saliva
      group), and 16 were pretreated with phosphate-buffered saline ([PBS] PBS group)
      at 37 degrees C for 1 hour. Hydrophobicity of the newly polymerized and water
      stored specimen surfaces was determined by contact angle measurements. C
      guilliermondii, C albicans, C glabrata, and C tropicalis were grown on tryptic
      soy agar. They were pretreated either with saliva or PBS and suspended in PBS.
      Four parallel test specimens were incubated without agitation in each yeast
      suspension at 37 degrees C for 1 hour, washed, and allowed to dry in air.
      Adherent cells were fixed, gram stained, and counted from 10 high-power light
      microscopy fields of each specimen. RESULTS: Enhanced adherence of yeasts was
      observed in water-stored test specimens in comparison to newly polymerized test
      specimens. Salivary pellicle reduced the hydrophobicity of test specimens and the
      adherence of yeasts. No differences in contact angles of distilled water between
      newly polymerized and water-stored polymers were observed. CONCLUSION: Yeasts
      seem to adhere less to newly polymerized than water-stored denture base polymer.
      This may be due to the release of residual monomer from the newly polymerized
      material.

PMID- 12066643
TI  - A transcultural perspective on the emotional effect of tooth loss in complete
      denture wearers.
AB  - PURPOSE: The purpose of this study was to compare the emotional effects of tooth
      loss in three edentulous populations. MATERIALS AND METHODS: A questionnaire
      study involved 142 edentulous subjects undergoing routine prosthodontic care at
      Guy's, King's and St Thomas's Dental Institute, London; the Dental School,
      Dundee, Scotland; and the Faculty of Dentistry, University of Hong Kong. Data
      were analyzed using the chi-squared test. RESULTS: Difficulty in accepting tooth
      loss was a relatively common experience (44%) in all groups, with almost half
      feeling that their confidence had been affected. The majority (66%) felt that
      their choice of food was restricted and that the overall eating experience was
      less enjoyable, particularly the Hong Kong group. A significant proportion of the
      participants were concerned about their appearance without dentures, although the
      trend was less marked in Hong Kong. Forty-three percent felt that they were not
      adequately prepared for tooth loss, although the Hong Kong group was least
      concerned. CONCLUSION: In general, the emotional effect of tooth loss was
      significant in all groups. The restrictions on daily activities were generally
      greater in the Hong Kong group. However, this group was much less inhibited by
      denture wearing. The differences observed in the Hong Kong Chinese are most
      likely due to different cultural values and expectations associated with these
      aspects of daily living.

PMID- 12066644
TI  - The role of prosthodontists in habilitation and rehabilitation in rare disorders:
      the ectodermal dysplasia experience.
AB  - PURPOSE: The aim of this article is to highlight the strong worldwide trend of
      enhancing the opportunities for individuals with rare disorders to get adequate
      information and treatment. Hypohidrotic ectodermal dysplasia is used as an
      example. MATERIALS AND METHODS: The development in recent years of databases for
      rare disorders, the establishment of resource centers in dentistry, and the
      strong movement of user influence by the formation of patient organizations and
      exchange of information through the Internet are described. Reference is made to
      the recent Scandinavian consensus conference on ectodermal dysplasia. RESULTS:
      Motives for the centralization of treatment planning to resource centers for
      persons with rare disorders, the compilation of treatment outcomes in databases,
      and the advocation of a multidisciplinary team approach in dentistry are
      presented. CONCLUSION: The prosthodontic profession has a key position in the
      habilitation and rehabilitation of many different diagnoses of rare disorders.

PMID- 12066645
TI  - Prosthetic habilitation of a young patient with hypohidrotic ectodermal dysplasia
      and oligodontia: a case report of 20 years of treatment.
AB  - PURPOSE: The aim of this article is to describe the oral habilitation, over a
      period of 20 years, of a young patient with hypohidrotic ectodermal dysplasia and
      agenesis of 15 permanent teeth. MATERIALS AND METHODS: Different clinical
      interventions were adapted to suit the patient's dental and psychologic stage of
      development. The prosthodontic treatment, which took place at different ages,
      comprised several treatment modalities: composite-retained onlay fixed partial
      dentures, a removable partial denture, tooth-supported and implant-supported
      fixed partial dentures, and laminate crown therapy. RESULTS: The different phases
      of treatment were successful, and the patient is satisfied from a functional as
      well as a psychosocial point of view. CONCLUSION: Extensive prosthodontic
      treatment in growing individuals should preferably be performed with a
      multidisciplinary team approach. In treatment that is planned and performed over
      long periods, this approach has the advantages of continuity and shared
      responsibility for therapy decisions.

PMID- 12066646
TI  - Metal-free inlay-retained fixed partial dentures.
AB  - OBJECTIVE: The treatment procedures used in conjunction with two different metal
      free restorative systems are illustrated on the basis of clinical examples. In
      addition, a report on the initial clinical findings is provided. METHOD AND
      MATERIALS: Metal-free restorative materials are opening doors to new preparation
      methods because of their close link to the adhesive cementation technique. As a
      result of the developments over the past few years, various metal-free systems
      that can be used to fabricate short-span fixed partial dentures (FPD) are now
      available. Certain guidelines, however, must be observed in the process. Because
      of their minimal invasiveness, inlay-retained FPDs offer an interesting solution
      in cases where the residual dentition exhibits low caries activity. Since the
      beginning of 1997, a total of 23 metal-free inlay-retained FPDs made of two
      different types of framework material (11 of high-strength pressed ceramic and 12
      of fiber-reinforced composite) have been examined in a clinical study. RESULTS:
      One inlay-retained FPD made of pressed ceramic had to be replaced because of a
      fracture. Because the materials have only been on the market for a short time,
      long-term results are not yet available. CONCLUSION: This type of restoration
      provides excellent esthetics and reduced invasiveness compared with complete
      crown-retained FPDs, although indications are limited by the special mechanical
      properties of the material.

PMID- 12066647
TI  - Bilateral talon cusp: case report.
AB  - Talon cusp is an uncommon condition often present in the maxillary incisors and
      mandibular premolars. Morphologically, this anomaly has a well-delineated cusp
      that extends at least half the distance from the cementoenamel junction or
      cingulum area to the incisal edge. The alteration can cause clinical problems
      such as caries or occlusal interference. Management of the talon cusp varies
      according to the circumstances of the individual case and should be as
      conservative as possible. Presented is a case of bilateral bifid talon cusp in
      maxillary central incisors that was successfully managed with conservative
      therapy.

PMID- 12066648
TI  - Support of undermined occlusal enamel provided by restorative materials.
AB  - OBJECTIVE: The purpose of this study was to test the support of occlusal enamel
      by amalgam (Dispersalloy), bonded amalgam (AmalgamBond Plus adhesive system with
      high-performance additive powder and Dispersalloy amalgam), and a bonded resin
      composite (Scotchbond Multi-Purpose adhesive system and Z100 resin composite).
      METHOD AND MATERIALS: For each material, 16 human molars were prepared. The
      lingual cusps were removed, and the dentin supporting the facial cusps was cut
      away, leaving a shell of enamel. Each group of prepared teeth was restored using
      the materials according to manufacturers' instructions. All specimens were
      thermocycled (1,500 cycles, 6 degrees C to 60 degrees C, dwell time 30 seconds),
      then mounted vertically in cast stone. A separating disk, mounted horizontally,
      was used to create a flat horizontal surface approximately 1.5 mm wide at the
      tips of both remaining enamel cusps of each specimen. Specimens were loaded
      evenly across the cusp tips at a crosshead speed of 10 mm/min until the fracture
      occurred. RESULTS: Data were analyzed using analysis of variance and Tukey A post
      hoc analysis. No significant difference was detected among amalgam, bonded
      amalgam, and bonded resin composite in their ability to support occlusal enamel.
      Support provided for occlusal enamel by the materials, whether bonded or not, was
      intermediate between no support and that provided by dentin. CONCLUSION: Without
      further development of materials technology and evidence of efficacy, restorative
      materials should not be relied upon to support undermined occlusal enamel.

PMID- 12066650
TI  - Unusual fracture of a mandibular second premolar: a case report.
AB  - Root fractures of posterior teeth, which are defined as fractures involving
      cementum, dentin, and pulp, are relatively uncommon among dental traumas. This
      study describes an unusual horizontal fracture of a mandibular second premolar.
      The tooth was asymptomatic and the fracture unnoticed until the crown broke off
      completely. The patient had no recollection of a causative event nor was there
      any evidence of previous physical trauma. The tooth was extracted, embedded in
      resin, sliced, and examined with different light microscopes. It was concluded
      that the tooth had been damaged previously but not to the extent that the pulp
      was seriously damaged. Resorption over a period of time eventually caused the
      final fracture.

PMID- 12066649
TI  - One-year retrospective clinical evaluation of hybrid composite restorations
      placed in United Kingdom general practices.
AB  - OBJECTIVE: The purpose of this study was to assess Pertac II restorations placed
      in general dental practice. METHOD AND MATERIALS: A total of 86 restorations (14
      Class I, 10 Class II, 17 Class III, 5 Class IV, and 40 Class V) using a hybrid
      composite material (Pertac II) placed in 56 patients (mean age, 39 years) in 5
      dental practices in the United Kingdom were assessed after 1 year by a trained
      evaluator and the dental practitioner who had placed the restoration. All the
      restorations were assessed for anatomic form, marginal adaptation, surface
      roughness, sensitivity or discomfort, gingival condition, and the presence or
      absence of secondary caries. RESULTS: Thirty-five (43%) restorations were placed
      in load-bearing situations, 9% of which were assessed as being in "heavy"
      occlusion. Five (6%) of the restorations were lost (all Class V restorations), 4
      from premolars and 1 from a molar. Four were in wedge-shaped cavities and 1 small
      restoration was actually dislodged during examination. The remaining 81 (94%)
      restorations were found to be intact, with no secondary caries detected. A high
      percentage of optimal scores were recorded for both anatomic form and surface
      roughness. CONCLUSION: It is concluded that the evaluation demonstrated
      satisfactory clinical performance of Pertac II restorations after 1 year of
      clinical service in the wide variety of clinical situations seen in general
      dental practice. However, the potential for failure of hybrid composite materials
      in Class V situations appears high. It may be argued that clinicians who wish to
      use a resin-based material in a Class V situation should use a compomer or
      microfilled composite.

PMID- 12066652
TI  - Computer-aided risk management--a software tool for the Hidep model.
AB  - OBJECTIVE: The Hidep risk management model has been developed and tested in
      clinical settings with promising results, but a tool facilitating the work has
      been suggested. The aim of the present study was to create and evaluate a
      computerized tool capable of creating overviews of the oral health situation as
      well as identifying risk factors and at-risk patients. The system developed
      should also facilitate the clinical work, for example, by assisting the user with
      automatic calculation of suitable Hidep groups and selection and printing of
      relevant patient information letters. METHOD AND MATERIALS: The system developed
      was based on the Hidep model, combining a number of available examination
      methods, risk estimation systems, and treatment suggestions. The development
      strategy included stepwise improvements and functionality increase based on
      continuous clinical applicability tests in a large international test bed.
      RESULTS: The results indicated that the software created was user friendly enough
      to be used in a common dental clinic and capable of handling the basic data of
      both patients and their oral health situation. The system could present useful
      statistics and graphs describing the overall oral health situation and
      identifying relevant risk groups and risk factors, based on virtually unlimited
      parameter combinations. CONCLUSION: The computer system developed seems to be an
      important step toward the possibility of creating a close-to-the-clinic model for
      oral health care management based on actual and locally derived patient data and
      risk factors. The results of this project encourage further studies of the Hidep
      model and its computer support.

PMID- 12066651
TI  - Generalized aggressive periodontitis in a prepubertal patient: a case report.
AB  - A 10-year-old boy presented with generalized gingival inflammation, extensive
      alveolar bone loss, and tooth mobility. Clinical and radiographic examination
      supplemented by microbiologic investigation led to a diagnosis of classically
      termed prepubertal periodontitis (now known as generalized aggressive
      periodontitis). Other than severe periodontitis, the child was systemically
      healthy. Neither unusual infections nor abnormalities in neutrophil functions
      were detected. Microbiologic examinations by culture revealed the presence of the
      periodontal pathogen Actinobacillus actinomycetemcomitans. Treatment consisted of
      extraction of mobile teeth, supragingival and subgingival debridement,
      subgingival curettage, and root planing combined with a 1-week prescription of a
      combination of metronidazole and amoxicillin. Scanning electron microscopy of
      extracted teeth revealed hypoplastic and aplastic cementum at the periodontally
      exposed and intact surfaces. Clinical and microbiologic follow-up was continued
      over a 1-year period. No periodontal lesions have been detected, and A
      actinomycetemcomitans could not be isolated from the subgingival areas of the
      remaining teeth at the end of the first year. Since A actinomycetemcomitans was
      the main pathogen present in the subgingival microflora of the patient, it might
      play a key role in the etiology of prepubertal periodontitis.

PMID- 12066653
TI  - Moral leadership in academic dentistry: the story of Jeanne Craig Sinkford.
AB  - Jeanne Craig Sinkford graduated from Howard University College of Dentistry in
      1958 and there began a career in academic dentistry as a clinical instructor. Six
      years later, armed with specialty training in prosthodontics and a master's
      degree and PhD in physiology from Northwestern University, Dr Sinkford returned
      to Howard expecting to develop a research program and continue her clinical
      teaching. Instead, she was immediately made head of the Department of
      Prosthodontics and in 11 more years became Howard's dean of dentistry. After 16
      years as dean, Dr Sinkford retired and took a position at the American Dental
      Education Association charged with developing and implementing policy on issues
      involving gender and minorities in dentistry. In addition to her reputation for
      her principled approach to getting things done, Dr Sinkford is widely recognized
      for her dedicated sincerity, her warmth, her concern for others, and her
      "reasoned reasonableness."

PMID- 12066654
TI  - Clinical images in oral medicine and maxillofacial radiology. Odontomas.

PMID- 12066655
TI  - How to check your bonding agent for effectiveness.

PMID- 12066656
TI  - Dentistry at the end: the hardest decision of all.

PMID- 12066657
TI  - Amelogenesis imperfecta: diagnosis and resolution of a case with hypoplasia and
      hypocalcification of enamel, dental agenesis, and skeletal open bite.
AB  - A case of amelogenesis imperfecta with hypoplasia, hypocalcification of the
      enamel, congenital absence of teeth 12 and 22, delayed eruption of tooth 23, edge
      to-edge incisal relationship, open bite, and bilateral posterior cross bite at
      the level of the first and second premolars is presented. Lateral skull
      teleradiography indicated a Class III skeletal pattern of maxillary origin
      associated with a dolichofacial pattern with multiple indicators of facial
      hyperdivergence. The patient presented a major esthetic abnormality of the face
      and required orthodontic treatment prior to a prosthetic solution with full
      coverage metal-ceramic crowns in both the maxilla and the mandible. The diagnosis
      of cases such as this one and the therapeutic implications from an orthodontic
      and prosthetic standpoint are reported.

PMID- 12066658
TI  - Burs with guide pins for standardized tooth preparation.
AB  - OBJECTIVE: The aim of this study was to develop and test self-limiting diamond
      burs to ease precise chamfer preparation and to fulfill the special requirements
      of computer-aided design/computer-aided manufacturing and all-ceramic
      restorations. METHOD AND MATERIALS: Rounded cylinder (based on ISO 881) and
      torpedo (based on ISO 879) diamond burs with a polished guide pin, 0.5 mm in
      length and 0.15 mm in radius, at the front end were developed in cooperation with
      an industrial partner. The in vitro testing involved a total of 140 human teeth.
      Experimental variables were the quality of the finish line, the microhardness of
      the enamel, and the thermal alteration of the dentin. Conventional diamonds
      served as a control. RESULTS: No mechanical or thermal damage related to the bur
      design was found in the hard tissues that had potentially been in contact with or
      in close proximity to the guide pin. Microhardness of the enamel at the finish
      line was significantly higher when prepared with burs with a guide pin compared
      to conventional burs. The results of using the guide pin might indicate the
      beneficial effect of reduced vibration. CONCLUSION: The guide pins of the self
      limiting diamond burs reduce, rather than increase, the risk of hard tissue
      damage at the preparation margin. No adverse effects were found. Clinical use is
      justified.

PMID- 12066659
TI  - A 5-year clinical study of indirect and direct resin composite and ceramic
      inlays.
AB  - OBJECTIVE: The aim of this investigation was to evaluate the clinical performance
      of 4 types of tooth-colored inlays. METHOD AND MATERIALS: Fifteen direct ceramic
      inlays (Cerec Cos 2.0), 15 direct resin composite inlays (Brilliant Direct
      Inlay), 14 indirect ceramic inlays (Vita Dur N), and 14 indirect resin composite
      inlays (Estilux) were made in 37 patients, according to the manufacturers'
      instructions. The inlays were evaluated 1 week (baseline) and 6, 12, 36, 48, and
      60 months after cementation (modified CDA Quality Evaluation System). RESULTS:
      Two Vita Dur N inlays fractured after 1 and 4 years in function, and one Cerec
      inlay fractured after 4.5 years. Two Brilliant DI inlays needed replacement
      because of secondary caries (after 1 and 5 years), and one inlay (Estilux) needed
      replacement due to persisting hypersensitivity. Three inlays (1 Estilux and 2
      Brilliant DI) were repaired due to chipping or minor fractures. During the
      observation period, the surface texture of Brilliant DI and Vita Dur N inlays
      became significantly rougher. After 5 years, the Estilux inlays had significantly
      lower ratings for morphology compared to baseline ratings. In general, the
      occlusal marginal adaptation did not show further disintegration of the luting
      cement after 1 year. CONCLUSION: Eighty-eight percent of the inlays were in
      function after 5 years. No significant differences were revealed among the
      survival rates of the different types of inlays.

PMID- 12066660
TI  - Fracture toughness of posterior resin composites.
AB  - OBJECTIVES: The purpose of this study was to evaluate and compare the resistance
      to crack propagation, as measured by the fracture toughness, of some packable
      posterior resin composites with other posterior resin composite materials. METHOD
      AND MATERIALS: Fracture toughness determinations were made for the 5 packable and
      the other posterior resin composites using 3-point flexure of beams with a
      standardized central single-edge notch. Ten beams of each material were tested on
      an Instron test machine. The maximum loads were determined, from which the
      fracture toughness values (KIC) were calculated. The data were analyzed
      statistically using ANOVA and t tests. RESULTS: The resin composites tested
      demonstrated a range of KIC values. The materials were separated according to the
      mean KIC values into 5 groups that were statistically different. While 2 packable
      resin composites had KIC values that were among the highest, the other packables
      were substantially lower than nonpackables. The intermediate value group
      consisted of 3 of the conventional posterior resin composites. CONCLUSION: There
      was a very weak correlation between fracture toughness and reported volume
      concentration of particulate reinforcing elements. The posterior resin composites
      tested exhibited a spectrum of KIC values. The packable resin composites were
      distributed along this spectrum, with 2 products exhibiting high potential for
      resistance to crack propagation.

PMID- 12066661
TI  - Pulp response and cytotoxicity evaluation of 2 dentin bonding agents.
AB  - OBJECTIVE: This study evaluated the biocompatibility of two dentin bonding agents
      (Clearfil Liner Bond 2 and Scotchbond Multi-Purpose) applied in human dental
      pulps and cell cultures. METHOD AND MATERIALS: In vivo: Twenty human third molars
      that were scheduled for extraction were used. After cavity preparation, pulp
      exposure was achieved with a carbide bur. Hemorrhage control was obtained with
      saline solution. In 16 teeth, adhesive pulp capping was performed and the
      cavities were sealed with resin composite. In the control group (n = 4), pulps
      were capped with Ca(OH)2 and the cavities were sealed with IRM. Teeth were
      extracted 30 or 90 days following treatment and prepared for histological
      examination and bacterial detection. In vitro: materials were applied in Petri
      dishes, where NIH-3T3 cells were plated. The cells were counted 2, 4, and 6 days
      after plating to obtain the growth curves and to determine cell viability. All
      data were submitted to statistical analysis. RESULTS: In vivo: Dentin bridge
      formation was seen in all teeth capped with Ca(OH)2, without an inflammatory
      response. Mild inflammatory responses and dentin bridge formation after 90 days
      were observed in 50% of specimens treated with Liner Bond 2. Pulps treated with
      Scotchbond Multi-Purpose presented mild to severe inflammatory response, and no
      mineralized tissue formation was detected. Bacteria were not disclosed in any
      specimen. In vitro: The cytotoxicity was similar between the two bonding agents,
      and both had statistically higher cytotoxic effects (P < 0.002) than Ca(OH)2.
      CONCLUSION: Ca(OH)2 produced pulp healing in all teeth and exhibited lower
      cytotoxic effects than both adhesive systems; however, pulp healing was also
      observed under Liner Bond 2.

PMID- 12066662
TI  - The patient with Alzheimer's disease.
AB  - Victims of Alzheimer's disease show a gradual and steady deterioration in memory,
      orientation, emotional stability, language capacity, abstract thinking, motor
      skills, and, ultimately, self care. Cognitive and motor deficits are accompanied
      by a gradual inability to perform adequate oral hygiene. Alzheimer's disease also
      interferes with the patient's ability to communicate dental symptoms of pain or
      dysfunction, and progressive deterioration of cognition interferes with the
      patient's ability to tolerate most therapeutic interventions. When treating
      patient's with Alzheimer's disease, oral health care providers must develop
      timely, preventive, and therapeutic strategies compatible with the patient's
      physical and cognitive ability to undergo and respond to dental care. They should
      strive to achieve those goals with the same ethical, moral, and professional
      standards of care as may be appropriate in the management of any other patient.

PMID- 12066664
TI  - Management of an impacted, dilacerated mandibular left permanent first molar: a
      case report.
AB  - A case of an unerupted mandibular left permanent first molar, a partially erupted
      permanent second molar, and a congenitally absent third molar in a 12-year-old
      girl is described. The permanent first molar, being dilacerated and impacted,
      required surgical exposure of the crowns of the first and second molars and
      distalization of the second molar, with the help of a space regainer, to bring
      the molars into occlusion.

PMID- 12066663
TI  - Diplopia as a complication of local anesthesia: a case report.
AB  - Diplopia caused by local anesthesia at the superior posterior alveolar nerve for
      the removal of the maxillary third molar is a rare complication. The diplopia is
      due to facial palsy of the oculomotor muscles of the globe. This paper describes
      the case of a 22-year-old woman, in whom diplopia was observed after an overall
      uncomplicated removal of the semi-impacted third molar. Possible causes of the
      anesthetic effects are reported. The most accepted explanation is that the
      anesthetic diffuses on the abducent nerve in the cavernous sinus. The necessary
      actions that the dental surgeon must perform are reported.

PMID- 12066665
TI  - Ease of use versus clinical effectiveness of restorative materials.
AB  - "Ease of use," as applied to dental materials and techniques, means different
      things to different people. Factors that may contribute to ease of use include a
      minimum number of application stages, easy application and shaping ability,
      quickness of use, lack of stick, and moisture sensitivity. Ease of use may also
      imply that a material or technique does not cause stress for the dentist and
      patient, is cost effective, is easy to learn, and should provide the operators
      with a sense of satisfaction with their work. Similarly, "clinical effectiveness"
      of the treatments prescribed for patients is not always capable of being
      accurately defined. Suggested factors that may contribute to clinical
      effectiveness include a lack of patient complaints with respect to longevity
      and/or cost, no secondary caries, and preservation of the remaining tooth
      structure during functional loading. Ease of use and clinical effectiveness are
      not necessarily related, but they must be combined for a technique to be
      successful. The achievement of this demands a partnership between clinicians,
      manufacturers, and patients.

PMID- 12066666
TI  - Aluminum oxide air abrasion particles: a bacteriologic and SEM study.
AB  - OBJECTIVE: The objective is to determine if aerobic and anaerobic sampling yields
      viable biologic contaminants in the aluminum oxide air abrasion powder as
      delivered by the manufacturer and to determine mean particle size for comparison
      with the published size from manufacturers and the range of sizes in the powders.
      METHOD AND MATERIALS: Samples from 15 unopened aluminum oxide powder containers
      from 9 different manufacturers were plated on aerobic and anaerobic culture
      media. The cultures were incubated at 35 degrees C and observed at 24-hour
      intervals. Samples of each of the 15 groups were subjected to scanning electron
      microscope (SEM) examination. Photomicrographs were obtained and a range and mean
      particle size determined. RESULTS: Aerobic and anaerobic cultures demonstrated no
      growth in any of the samples. Mean particle size determined by SEM for 25- to
      27.5-micron particles ranged from 27.3 microns to 32.0 microns with standard
      deviations from 1.06 microns to 7.70 microns. Mean particle size for 50 microns
      particles ranged from 51.6 microns to 59.7 microns with standard deviations of
      5.48 microns to 14.80 microns. CONCLUSION: Aluminum oxide powders as delivered by
      manufacturers appeared to be free from viable microorganisms. The powder mean
      particle sizes approximate the labeled sizes closely enough such that they should
      perform properly in air abrasion tooth preparation.

PMID- 12066668
TI  - Clinical images in oral medicine and maxillofacial radiology. Taurodontism.

PMID- 12066667
TI  - Constancy of bond strength in 5 single-bottle dentin bonding systems.
AB  - OBJECTIVE: Historically, wide variations in the shear bond strength of resin
      composite bonded to dentin have been reported. The purpose of this study was to
      compare 5 commercially available single-bottle dentin bonding systems while
      controlling several sources of variation in shear bond strengths. METHOD AND
      MATERIALS: Extracted molars were stored for 2 weeks in 0.5% Chloramine T. The
      teeth were mounted, the occlusal enamel was removed to expose middle dentin, and
      the exposed dentin was etched and treated according to 1 of 6 protocols. Finally,
      a cylinder of resin-based composite was bonded to the dentin. After 24 hours,
      specimens were fractured under shear force, and the results were recorded in
      megapascals. RESULTS: The type of product used was significantly associated with
      the mean shear bond strength observed. All products exhibited some degree of
      variation from specimen to specimen. One product, PQ1, exhibited less variation
      than the other 4 products. CONCLUSION: PQ1 was found to have a significantly
      higher mean shear bond strength than the other 4 products tested. There was no
      significant difference between specimens bonded to dry dentin and specimens
      bonded to wet dentin when using PQ1.

PMID- 12066669
TI  - Improving dentist-patient relations.

PMID- 12066671
TI  - Biomechanical effects of cervical lesions and restoration on periodontally
      compromised teeth.
AB  - OBJECTIVE: The purpose of this study was to photoelastically evaluate the effects
      of cervical root lesions and their restoration on stress distribution in
      periodontally compromised teeth. METHOD AND MATERIALS: Three-dimensional
      composite photoelastic models of a maxillary first premolar with buccal cervical
      root lesions were fabricated. Two different lesion configurations, wedge- and
      shallow saucer-shaped, at 20% alveolar bone height reduction were tested. A 35%
      reduction model was given a wedge-shaped lesion. The lesions were restored with
      microfine resin composite. Vertical loads of 7.5 lbs were applied to the
      unrestored and restored models at the tip of the buccal cusp and the tip of the
      lingual cusp. The resulting stresses within the tooth models were monitored and
      recorded photographically in the field of a circular polariscope arrangement.
      RESULTS: For buccal cusp loading of the unrestored models, stress concentrated at
      the apex of the lesion regardless of the lesion shape or periodontal support
      conditions. The highest stress concentration was observed around the apex of the
      wedge-shaped lesion on the 35% reduction model. Restoring the lesions changed
      stress distribution. Restoration of the lesions resulted in a marked stress
      reduction at the lesion apex. Stress along the gingival restoration-model
      interface was characteristic for the restored situation. The interfacial stress
      followed the contour of the restoration most closely for the wedge-shaped lesion
      on the 20% support reduction model. CONCLUSION: The shape and dimension of the
      lesion as well as periodontal support status has considerable influence on stress
      distribution, especially around the lesion, restored or not restored.

PMID- 12066670
TI  - Tray delivery of potassium nitrate-fluoride to reduce bleaching sensitivity.
AB  - OBJECTIVE: Tooth sensitivity is a common side effect associated with tooth
      whitening. The purpose of this study was to determine if bleaching tray delivery
      of potassium nitrate-fluoride reduces bleaching sensitivity enough to allow
      continuation of whitening treatment. METHOD AND MATERIALS: Thirty patients were
      enrolled in a university-approved clinical study and had their teeth bleached at
      night with 10% carbamide peroxide in a custom-fitted tray. The bleaching tray was
      a rigid experimental design for which sensitivity was expected. If tooth
      sensitivity was experienced, the patient applied a gel containing 5% potassium
      nitrate and 1,000 ppm sodium fluoride in the bleaching tray for various time
      periods. Log forms were collected upon completion of bleaching, and patient
      interviews were used to compare effects of the gel before and after sensitivity
      treatment. RESULTS: Sixteen out of 30 patients experienced tooth sensitivity. Of
      those 16 patients, 12 used the gel, and 11 of the 12 reported a reduction in
      sensitivity. Treatment times ranged from 10 minutes before bleaching to 30
      minutes before and after. The number of applications ranged from one to
      continuous use. Some patients were able to continue bleaching after one gel
      application with no subsequent sensitivity. Other patients were unable to
      continue bleaching unless they continued using the gel. The incidence of tooth
      sensitivity (53%) reported in this study is consistent with sensitivity reported
      in studies using semi-rigid custom-fitted trays made from stone casts with a
      nonscalloped, nonreservoir design. CONCLUSION: The use of a 5% potassium nitrate
      fluoride gel applied in the tray as needed for tooth sensitivity associated with
      nightguard vital bleaching can reduce sensitivity in a majority of patients and
      allow most patients to continue bleaching to completion.

PMID- 12066672
TI  - The influence of surface configuration on the retention of posts designed for use
      with a cast-on technique.
AB  - OBJECTIVES: The combination of an individually cast core and a prefabricated
      metal post is one of the many techniques to restore endodontically treated teeth.
      The surface characteristics of commercially available posts vary considerably and
      likely influence retention. In this study, the surface configuration of 11
      castable prefabricated post systems and their retention at the post-cement
      interface were investigated. METHOD AND MATERIALS: Scanning electron microscopic
      photos were made to assess surfaces of the posts. Etchant residues or applied
      surface layers were also analyzed with an electron beam microprobe. For the
      retention measurements, 6 posts from each system were cemented in artificial root
      canals with a zinc phosphate cement. Retention was measured on a universal
      testing machine. RESULTS: Analysis of variance and the Ryan-Einot-Gabriel-Welsch
      F test revealed significant differences in retention between posts; these
      differences were related to the microstructure of the surfaces of the posts. In
      general, the coarser the surfaces, the better the retention. Gold plating of the
      etched surface for one manufacturer resulted in less retention compared to posts
      of the same type and size that were not plated. CONCLUSION: The surface
      configuration of a post could be an important factor when selecting a
      prefabricated post system.

PMID- 12066673
TI  - Detection of Helicobacter pylori colonization in dental plaques and tongue
      scrapings of patients with chronic gastritis.
AB  - OBJECTIVE: It has been suggested that the oral cavity and dental plaque might be
      a reservoir for Helicobacter pylori (Hp). In this study, our aims were to detect
      the prevalence of Hp colonization in dental plaque and tongue scrapings of
      patients with chronic gastritis and to investigate the effect of systemic
      treatment upon this colonization and eradication of Hp from gastric mucosa.
      METHOD AND MATERIALS: Eighty-one patients (49 men, 32 women) were included in the
      study. Dental plaque and tongue scraping specimens were obtained and assessed
      with Campylobacter-like organism (CLO) test, prior to endoscopic examination. By
      endoscopy, 2 antral and 1 corpus biopsy samples were taken for histologic
      examination, and 1 antral biopsy sample was taken for CLO test examination.
      RESULTS: Chronic gastritis was diagnosed in 63 (77.7%) of 81 patients. Dental
      plaque samples of 64 (79%) patients and tongue scraping samples of 48 (59.2%)
      patients were urease positive. Of the 63 patients with chronic gastritis, dental
      plaque and tongue scrapings were urease positive in 52 (83%) and 37 (59%)
      patients, respectively. After 14 days of triple drug therapy (omeprazole,
      clarithromycin, and amoxicillin), Hp was eradicated from the gastric mucosa of
      almost all of the patients, whereas no changes were detected in dental plaque and
      tongue scrapings by CLO test examination. CONCLUSION: Helicobacter pylori
      colonization, which seemed to be high in dental plaque and on the tongue, might
      play an important role in the pathogenesis of the reinfection process. In order
      to eradicate Hp from both the oral cavity and the gastric mucosa, studies should
      be performed to assess the effects of plaque control procedures in addition to
      present treatment modalities.

PMID- 12066674
TI  - Principles and application of learning theory in child patient management.
AB  - General dentists, as well as pediatric dentists, treat many children. Behavior
      management for children is an integral component of pediatric dental practice.
      Behavior management techniques have been developed based on empirical evidence
      indicating the importance of social learning theory to change both the causes and
      consequences of negative behaviors. This paper addresses the theoretical basis of
      current approaches in guiding children's behavior during dental settings. The
      relevance of the theoretical areas to the day-to-day treatment of the patient is
      emphasized.

PMID- 12066675
TI  - Effect of calcium removal on dentin bond strengths.
AB  - OBJECTIVE: The purpose of this in vitro study was to determine the microtensile
      bond strengths (mu TBS) of 3 dental adhesives when applied to dentin decalcified
      with ethylenediaminetetraacetic acid (EDTA). The null hypothesis tested was that
      the removal of calcium from dentin would not influence the bond strengths. METHOD
      AND MATERIALS: Eighteen extracted human molars were cut in 2 equal halves. One
      half served as the control, having no EDTA treatment, while the other half was
      assigned to 1 of 3 periods (1 hour, 24 hours, or 100 hours) of decalcification
      with buffered 0.5 mol/L EDTA. Middle dentin was bonded with 1 of 3 dentin
      adhesive groups: a self-etching primer, Clearfil SE Bond (SE); an acetone-based
      total-etch adhesive, Prime&Bond NT (NT); and an ethanol- and water-based total
      etch adhesive, Single Bond (SB). The specimens were restored with Z-250 resin
      composite and sectioned in 0.9 +/- 0.2 mm2 sticks that were tested in tensile
      mode. RESULTS: For each adhesive, the control group (not decalcified) resulted in
      statistically higher bond strengths than the treatment groups. For specimens that
      were not decalcified, SE and SB had statistically similar bond strengths, but
      both resulted in statistically higher bond strengths than NT. For specimens
      decalcified for 1 hour, SE resulted in statistically higher bond strengths than
      either SB or NT, which were ranked in the same statistical group. SE was the only
      dentin adhesive to result in measurable mu TBS after decalcification with EDTA
      for 24 hours, while SB/24 hour and NT/24 hour specimens debonded spontaneously
      prior to testing. All the specimens treated with EDTA for 100 hours debonded
      prior to testing. CONCLUSION: Three conclusions were drawn: (1) All 3 adhesive
      systems included in this project bonded significantly better to calcified than to
      decalcified dentin, regardless of their composition; (2) The self-etching primer
      based adhesive ranked consistently equal to or better than the 2 total-etch-based
      adhesives, regardless of the EDTA decalcification time; and (3) Removal of
      calcium may be more detrimental for adhesives that rely on dentin acid etching
      than for adhesives based on self-etching primers.

PMID- 12066677
TI  - Activism for access to care: the story of Jack A. Whittaker.

PMID- 12066676
TI  - Effect of sonic and mechanical toothbrushes on subgingival microbial flora: a
      comparative in vivo scanning electron microscopy study of 8 subjects.
AB  - OBJECTIVES: The purpose of this initial study was to evaluate the effects of both
      a sonic and a mechanical toothbrush versus the effects of no treatment on depth
      of subgingival penetration of epithelial and tooth-associated bacteria. METHOD
      AND MATERIALS: Eight adult subjects exhibiting advanced chronic periodontitis
      with at least 3 single-rooted teeth that were in separate sextants with facial
      pockets > or = 4 mm and < or = 8 mm and that required extraction constituted the
      experimental sample. Teeth were either subjected to 15 seconds of brushing with a
      mechanical toothbrush or a sonic toothbrush or left untreated. The test tooth and
      the associated soft tissue wall of the periodontal pocket were removed as a
      single unit. Samples were processed and coded for blind examination by scanning
      electron microscopy. Distributional and morphologic characteristics of dominant
      bacteria with specific emphasis on spirochetes were evaluated for both epithelial
      and tooth-associated plaque. RESULTS: No differences were found in morphotypes
      or distributional and aggregational characteristics of epithelial-associated
      microbes in the 1- to 3-mm subgingival zone between the mechanical and sonic
      toothbrush-treated groups and the control group. Both toothbrush groups featured
      disruption of microbes that extended up to 1 mm subgingivally. Root surfaces on
      the sonic-treated samples appeared plaque-free at low magnification; however, at
      4,700x, a thin layer of mixed morphotypes and intact spirochetes was found
      subgingivally and slightly subgingivally. In comparison, mechanical brush samples
      featured incompletely removed plaque, both subgingivally and subgingivally, with
      intact spirochetes present on subgingival root surfaces. CONCLUSION: Results
      suggest similar effects for both sonic and mechanical toothbrushes on epithelial-
      and tooth-associated bacterial plaque in periodontal pockets and adjacent root
      surfaces that extend up to 1 mm subgingivally. Further, the presence of intact
      subgingival spirochetes suggests limited exposure to acoustical or mechanical
      energy from the toothbrushes evaluated.

PMID- 12066678
TI  - The dental ferrule and the endodontically compromised tooth.

PMID- 12066680
TI  - The world's elderly: another aspect.

PMID- 12066679
TI  - Clinical images in oral medicine and maxillofacial radiology. Neurofibromatosis.

PMID- 12066681
TI  - A new therapeutic classification of cavities.

PMID- 12066682
TI  - Chairside prefabricated fiber-reinforced resin composite fixed partial dentures.
AB  - The introduction of pre-impregnated fiber-reinforced resin composites has
      provided the dental profession with the opportunity to fabricate and deliver
      adhesive, esthetic, and metal-free tooth replacements. Utilizing this technology,
      a prefabricated fiber-reinforced resin composite fixed partial denture prototype
      that allows rapid, cost-effective, and noninvasive fixed tooth replacement for
      single anterior teeth has been developed. Ideal situations for this type of
      service include: a fixed replacement following tooth loss from trauma; a fixed
      tooth replacement in medically compromised patients who cannot sit for extended
      periods of time or have local anesthesia; periodontally compromised abutments; a
      fixed space maintainer following orthodontic movement; and a fixed provisional
      during the post implant healing phase prior to loading. This article describes
      the framework construction and placement protocol for the prefabricated fiber
      reinforced resin composite fixed partial denture.

PMID- 12066683
TI  - Reassessment of homology of morphological characters in tetractinellid sponges
      based on molecular data.
AB  - In sponges, as in other taxa with simple organization, the evaluation and use of
      morphological characters is difficult. Phylogenetic analysis of the first 850
      nucleotides from the 5' end of the 28S rRNA gene is used here to assess the
      homology of spicules used in the classification of the subclass Tetractinellida.
      A single well-supported MP tree was obtained. The monophyly of the nine
      Tetractinellida species studied confirms the tetraxon megasclere as a
      morphological synapomorphy for the Tetractinellida. Two species are reallocated,
      Penares helleri as a Geodiidae, now thought to have lost sterraster microscleres,
      and Stryphnus mucronatus to the Streptosclerophorida. SEM micrographs of
      Stryphnus microscleres show that the morphology of the sanidasters is compatible
      with the hypothesis that they are homologous with streptoscleres and confirm this
      reallocation. Two other synapomorphies are confirmed within the tetractinellid
      clade, the simultaneous presence of tetraxon megasclere and aster-type
      microsclere (Astrophorida) and the loss of the streptosclere and persistence of
      the euaster s.s. microscleres (Euastrophorida) evidenced by the reallocation of
      Stryphnus mucronatus. The streptosclere microscleres cannot be evaluated in terms
      of homology because Streptosclerophorida may be paraphyletic (although these
      nodes are not supported by reliable bootstrap proportions) contrary to the
      currently accepted classification.

PMID- 12066685
TI  - The accuracy of methods for coding and sampling higher-level taxa for
      phylogenetic analysis: a simulation study.
AB  - Many phylogenetic analyses, particularly morphological studies, use higher taxa
      (e.g., genera, families) rather than species as terminal taxa. This general
      approach requires dealing with interspecific variation among the species that
      make up the higher taxon. In this paper, I review different parsimony methods for
      coding and sampling higher taxa and compare their relative accuracies using
      computer simulations. Despite their widespread use, methods that involve coding
      higher taxa as terminals perform poorly in simulations, relative to splitting up
      the higher taxa and using species as terminals. Among the methods that use higher
      taxa as terminals, coding a taxon based on the most common condition among the
      included species (majority or modal coding) is generally more accurate than other
      coding methods, such as coding taxa as missing or polymorphic. The success of the
      majority method, and results of further simulations, suggest that in many cases
      "common equals primitive" within variable taxa, at least for low and intermediate
      rates of character change. The fixed-only method (excluding variable characters)
      performs very poorly, a result that is indirectly supported by analyses of
      published data for squamate reptiles. Sampling only a single species per higher
      taxon also yields low accuracy under many conditions. Along with recent studies
      of intraspecific polymorphism, the results of this study show the general
      importance of (1) including characters despite variation within taxa and (2)
      using methods that incorporate detailed information on the distribution of states
      within variable taxa.

PMID- 12066684
TI  - Data sets, partitions, and characters: philosophies and procedures for analyzing
      multiple data sets.
AB  - We compared four approaches for analyzing three data sets derived from
      staphylinoid beetles, a superfamily whose known species diversity is roughly
      comparable to that of vertebrates. One data set is derived from adult morphology
      and the two molecular data sets are from 12S ribosomal RNA and cytochrome b
      mitochondrial DNA. We found that taxonomic congruence following conditional data
      combination, herein called compatible evidence (CE), resolved more nodes
      compatible with an initial conservative hypothesis than did total evidence (TE),
      conditional data combination (CDC), or taxonomic congruence (TC). CE sets a base
      of nodes obtained by CDC analysis and then investigates what further agreement
      may arise in a universe where these nodes are accepted as given. We suggest that
      CE75-75 may be appropriate for future studies that aim to both generate a well
      corroborated tree and investigate conflicts between data sets, partitions, and
      characters. CE75-75 is a 75% bootstrap consensus CDC tree followed by combinable
      component consensus of a 75% bootstrap consensus of each homogeneous set of
      partitions having hierarchical structure.

PMID- 12066686
TI  - Weighted ancestral area analysis and a solution of the redundant distribution
      problem.
AB  - A new cladistic method for the estimation of ancestral areas is based on
      reversible parsimony in combination with a weighting scheme that weights steps in
      positionally plesiomorphic branches more highly than steps in positionally
      apomorphic branches. By applying this method to cladograms of human mitochondrial
      DNA, the method is superior to previously proposed algorithms. The method is also
      an appropriate tool for the solution of the redundant distribution problem in
      area cladograms. Under the assumption of allopatric speciation, redundant
      distributions, i.e., sympatry of sister groups, show that dispersal has occurred;
      thus, the ancestral area of at least one sister group was smaller than the
      combined distribution of its descendants. With the weighted ancestral area
      analysis, the ancestral areas can be confined and at least some dispersal events
      can be distinguished from possible vicariance events. As applied to a cladogram
      of the Polypteridae, weighted ancestral area analysis is superior to Brooks
      parsimony analysis (assumption 0) and component analysis under assumptions 1 and
      2 (Nelson and Platnick, 1981, Systematics and biogeography: Cladistics and
      vicariance. Columbia Univ. Press, New York.) in resolving redundancies. The
      results of the weighted ancestral area analysis may differ from the results of
      dispersal-vicariance analysis, because the rules of dispersal-vicariance analysis
      indirectly favor the questionable assumption that the ancestral species occupied
      only one unit area.

PMID- 12066687
TI  - The phylogenetic position of the musky rat-kangaroo and the evolution of bipedal
      hopping in kangaroos (Macropodidae: Diprotodontia).
AB  - Kangaroos and their relatives (family Macropodidae) are divided into the
      subfamilies Macropodinae (kangaroos, wallabies, pademelons) and Potoroinae (rat
      kangaroos, potoroos, bettongs). The musky rat-kangaroo, Hypsiprymnodon moschatus,
      is traditionally allied with other potoroines, based primarily on the basis of
      osteological characters and aspects of the female reproductive system. Unlike
      other macropodids, however, which are capable of bipedal hopping, Hypsiprymnodon
      is a quadrupedal bounder and lacks several derived features of the pes and tarsus
      that are presumably adaptations for bipedal hopping. Other derived features, such
      as a complex stomach, loss of P2 with the eruption of P3, and reduction of litter
      size to one, are also lacking in Hypsiprymnodon but occur in all other
      macropodids. Thus, available evidence suggests that Hypsiprymnodon either is part
      of a monophyletic Potoroinae or is a sister taxon to other living macropodids. To
      test these hypotheses, we sequenced 1,170 bp base pairs of the mitochondrial
      genome for 16 macropodids. Maximum parsimony, minimum evolution, maximum
      likelihood, and quartet puzzling all support the hypothesis that macropodines and
      potoroines are united to the exclusion of Hypsiprymnodon. This hypothesis implies
      that characters such as bipedal hopping evolved only once in macropodid
      evolution. Aside from Hypsiprymnodon, the remaining macropodids separate into the
      traditional Macropodinae and Potoroinae. Macropodines further separate into two
      clades: one containing the New Guinean forest wallabies Dorcopsis and
      Dorcopsulus, and one consisting of the genera Macropus, Setonix, Thylogale,
      Onychogalea, Wallabia, Dendrolagus, Peradorcas, and Lagorchestes. Among
      potoroines, there is moderate support for the association of Bettongia and
      Aepyprymnus to the exclusion of Potorous. Divergence times were estimated by
      using 12S ribosomal RNA transversions. At the base of the macropodid radiation,
      Hypsiprymnodon diverged from other macropodids approximately 45 million years
      ago. This estimate is comparable to divergence estimates among families of
      Australasian possums based on single-copy DNA hybridization and 12S rRNA
      transversions. Macropodines and potoroines, in turn, diverged approximately 30
      million years ago. Among macropodines, Dorcopsis and Dorcopsulus separated from
      other taxa approximately 10 million years ago.

PMID- 12066688
TI  - Incongruence between morphological and mitochondrial-DNA characters suggests
      hybrid origins of parthenogenetic weevil lineages (Genus aramigus).
AB  - An expanded matrix of morphological characters for the genus Aramigus
      (Coleoptera: Curculionidae), which includes numerous polyploid parthenogenetic
      lineages, was compared and combined with a published matrix of mitochondrial DNA
      (mtDNA) characters. The matrix of morphological characters provides little
      resolution of the A. tessellatus and A. uruguayensis species complexes but does
      resolve previously unresolved relationships among other morphologically defined
      species (A. globoculus + A. intermedius, A. curtulus + A. planioculus). The
      morphological and mtDNA characters are significantly incongruent (0.435 < or = IM
      < or = 0.463; IMF = 0.0735), according to the tests of Farris et al. (P = 0.010)
      and Templeton (P < 0.005), probably because of hybrid origins of polyploid
      parthenogenetic lineages. For the few sexual lineages included in both matrices,
      morphology and mtDNA provide congruent estimates of phylogeny. In spite of recent
      injunctions against combining data sets that are incongruent because of differing
      histories, the results of the combined analyses were used to select one of the
      most-parsimonious mtDNA trees as the best estimate of maternal-lineage genealogy
      and to reconstruct the evolution of parthenogenesis under the assumption that
      transitions from sexuality to parthenogenesis are irreversible. Where
      cytogenetically justified, as in weevils, the irreversibility assumption is
      useful for producing conservative estimates of the age of parthenogenetic
      lineages in spite of potential sampling bias against sexuals.

PMID- 12066689
TI  - Archiving molecular phylogenetic alignments as NEXUS files.

PMID- 12066690
TI  - Properties of matrix representation with parsimony analyses.

PMID- 12066691
TI  - Why morphometrics is not special: coding quantitative data for phylogenetic
      analysis.
AB  - Thorpe (1984) and Chappill (1989) argued that selection of a coding method should
      be [figure: see text] based on the purpose of coding. In our view, the purpose of
      coding is dictated by the principles of phylogenetic systematics. The foundation
      of phylogenetic systematics is the observation that monophyletic groups can be
      recognized if homologous character states, shared evolutionary novelties, can be
      identified (Hennig, 1966). Unfortunately, characters do not have labels
      indicating their homology. Instead, a systematist must propose a hypothesis of
      homology and evaluate its congruence with independent hypotheses based on other
      traits. In this context, the purpose of coding is to represent those hypotheses.
      The major obstacle to coding is that the a priori groups under analysis (i.e.,
      taxa) often have ranges of variation that overlap to some degree. This is true
      whether traits are described qualitatively or quantitatively. One advantage of
      quantitative description is that it permits a more detailed analysis of how much
      the ranges of variation overlap. It may seem appropriate to use statistical
      methods to summarize the amount of overlap and even to decide objectively (on a
      priori grounds) whether taxa are similar or different. Above, we demonstrated
      some of the problems resulting from these uses of statistical analysis. In our
      view, the most important problem is the implication that similarity of the
      feature across taxa is the basis for inferring homology. The similarity that is
      relevant to phylogenetic analysis is not proximity in morphospace, but shared
      novelty. Statistical methods can describe proximity, but they cannot recognize
      novelty. The method of coding we recommend uses graphical displays of individual
      values. Coding decisions are based on all of the individuals in each taxon, not
      on summaries derived from models of expected distributions. Then, the evidence
      for inferring divergence is independently evaluated for each pair of overlapping
      taxa. Coding decisions are not based on a priori rules that have no bearing on
      recognition of evolutionary novelty. This is the same approach that is used to
      code qualitatively described traits.

PMID- 12066692
TI  - Systematic bias in phylogenetic analysis: is the Strepsiptera problem solved?

PMID- 12066693
TI  - After September 11.

PMID- 12066695
TI  - Procera AllCeram crowns followed for 5 to 10.5 years: a prospective clinical
      study.
AB  - PURPOSE: This is a report on Procera AllCeram crowns in a prospective multicenter
      study. The aim of the study was to evaluate AllCeram crowns in dental practice
      over a 5- to 10.5-year period. Some of the AllCeram crowns were among the very
      first that were placed. MATERIALS AND METHODS: The crowns were placed between
      1989 and 1995. Twelve clinicians at nine clinics placed 87 crowns in 50 patients.
      The California Dental Association quality evaluation system was used for
      assessment of marginal integrity and esthetics. RESULTS: After 5 and 10 years a
      cumulative survival rate of 97.7% and 93.5%, respectively, and a cumulative
      success rate of 97.7% and 92.2%, respectively, was recorded. Six crowns (7%) were
      recorded as failures; five of these crowns (6%) had to be remade. The marginal
      integrity was considered excellent or acceptable for 92% of the crowns. Bleeding
      was somewhat more often recorded at teeth with AllCeram crowns (39%) than at
      contralateral teeth (27%). Endodontic treatment was performed for a low number
      (2%) of the AllCeram crowns. The patients found the esthetics to be excellent.
      CONCLUSION: The results of this study demonstrate about the same clinical outcome
      as has been reported by similar studies on all-ceramic crowns built on a core of
      alumina. The outcome is also in agreement with that reported for metal-ceramic
      crowns. The results indicate a good prognosis for Procera AllCeram crowns also
      for posterior teeth.

PMID- 12066694
TI  - Integration of 3-D shapes of dentition and facial morphology using a high-speed
      laser scanner.
AB  - PURPOSE: The purpose of this study was to develop a method to integrate three
      dimensional data of dentition and facial morphology measured by a high-speed
      laser scanner, and visualize them by computer graphics. The accuracy of
      integration was also examined. MATERIALS AND METHODS: The 3-D shapes of upper and
      lower dental casts and the face of a subject were measured by a high-speed laser
      scanner with zoom lens facility. As an interface to integrate the coordinates
      between dentition and face, an extraoral marker plate attached to the occlusal
      record plate was devised. It was applied between the upper and lower dental
      casts, and with the subject, and measured. Integration was attempted by
      coinciding the data of the interface. The accuracy of integration was examined
      using the conditions of the marker plate such as surface shape and attachment
      angle. RESULTS: Integration of the data of dentition and face was accomplished.
      The 3-D relationship between them could be visualized in any direction or section
      by computer graphics. For optimal accuracy of integration, the marker plate with
      a mixed shape of flat and sinusoidal wave attached at 45 degrees to the occlusal
      record plate showed the most appropriate results. CONCLUSION: An original method
      to integrate the 3-D data of dentition and face measured by 3-D laser scanner was
      developed and shown to have acceptable accuracy.

PMID- 12066697
TI  - Is there a benefit of using an arbitrary facebow for the fabrication of a
      stabilization appliance?
AB  - PURPOSE: The aim of this clinical study was to evaluate if an arbitrary facebow
      registration and transfer provides significant advantages for the fabrication of
      an occlusal appliance in comparison with the omission of such a procedure.
      MATERIALS AND METHODS: For 20 fully dentate adult patients diagnosed with
      bruxism, two Michigan occlusal splints were constructed. One of the two upper
      dental casts was transferred to the articulator with an arbitrary earpiece
      facebow; the other maxillary cast was mounted arbitrarily using a flat occlusal
      plane indicator. Upon splint delivery, the number of intraoral occlusal contacts
      and the time needed for chairside occlusal adjustment were recorded. RESULTS: The
      number of occlusal contacts on the appliance fabricated with or without facebow
      was similar in most cases both in the articulator and in the mouth. The one-sided
      Wilcoxon rank sum test showed with high probability that the use of an arbitrary
      facebow does not yield a clinically relevant improvement with regard to the
      number of occlusal contacts or the chairside adjustment time. CONCLUSION: From
      this pilot study, it appears that for the fabrication of an occlusal appliance,
      registration and transfer with an arbitrary earpiece facebow does not yield
      clinically relevant benefits. Of course, this conclusion cannot be transferred to
      other facebows and is restricted to the levels of clinical relevance defined in
      the study.

PMID- 12066696
TI  - Rigidity of three different types of mandibular major connector through vibratory
      observations.
AB  - PURPOSE: The purpose of this study was to investigate the vibration
      characteristics of three different designs of mandibular major connectors in
      vitro by observing modal animation, decay rate, and maximum amplitude. MATERIALS
      AND METHODS: Three removable partial denture frameworks--lingual bar, Kennedy
      bar, and lingual plate--were studied. They were excited by a shaker, and the
      frequency response functions were recorded on a Fast Fourier Transformational
      analyzer to identify their modal shapes. Natural frequency and animation of
      motion at each natural mode of vibration of the three frameworks were observed.
      In addition, transient response simulations were recorded, and decay rates and
      maximum amplitude of the resultant transient response waves were computed.
      RESULTS: The mean decay rate calculated from all the measurement points of the
      lingual bar, Kennedy bar, and lingual plate was 3.10 s-1 (standard deviation [SD]
      0.07), 2.42 s-1 (SD 0.04), and 2.01 s-1 (SD 0.03), respectively. Significant
      differences in decay rate were found among all pairs (P < .001). Maximum
      amplitude of the direct and indirect retainers at the nonimpacted side also
      differed (P = .008). CONCLUSION: All three designs demonstrated no elastic
      deformation at each natural mode of vibration. In terms of vibration analysis,
      the lingual bar demonstrated the maximum decay rate and the minimum maximum
      amplitude of the direct and indirect retainers, both on impacted and nonimpacted
      sides, indicating that the lingual bar will dissipate the energy through
      vibration faster than the other designs. Hence, the possibility of creating
      harmful effects to the oral tissue is lesser.

PMID- 12066698
TI  - Implant angulation: a measurement technique, implant overdenture maintenance, and
      the influence of surgical experience.
AB  - PURPOSE: The purposes of this study were to develop a technique to measure the
      angulation between two implants and between each implant and reference planes, to
      analyze the relationship between the maintenance (adjustments and repairs) of
      ball-attachment mandibular implant overdentures and implant angulation, and to
      see if there is any correlation between surgeon experience and implant
      orientation. MATERIALS AND METHODS: Final casts of 41 patients who had received
      two-implant ball-attachment mandibular overdentures were used to measure implant
      angulations using digital photographs and plane geometry. The measured angles
      were compared with the number of adjustments and repairs of the prostheses and
      analyzed by surgeon experience for any trends. RESULTS: No significant
      relationships were found between number of adjustments and repairs and the
      interimplant angles. However, there was a significantly higher number of repairs
      when the lingual inclination of an implant was > or = 6.0 degrees (P = .033) or
      if the facial inclination was < 6.5 degrees (P = .036). Less experienced surgeons
      had a significantly greater tendency to place implants that diverged from each
      other in the frontal plane (P = .045) and with a facial or lingual inclination in
      the sagittal plane (P = .035). CONCLUSION: While interimplant angulation did not
      appear to affect prosthesis maintenance, individual implants with a lingual
      inclination > or = 6 degrees and a facial inclination < 6.5 degrees were
      associated with significantly more prosthesis repairs. There was a tendency for
      implants placed by less experienced surgeons to demonstrate greater inclination.

PMID- 12066699
TI  - Assessment of shear bond strength between three denture reline materials and a
      denture base acrylic resin.
AB  - PURPOSE: This study reports the effect of five surface treatments on the bond
      strength established between three denture reline materials and a denture base
      resin. MATERIALS AND METHODS: Cylindric columns of denture reline materials were
      bonded to columns of denture base resins that received one of the surface
      treatments: application of dichloromethane, the monomer of the denture base
      resin, the recommended bonding agent or the monomer of the denture reline
      material, polishing with 240-grit silicone carbide paper, and air abrasion. A
      control group without surface treatment was included for each material. Specimens
      were immersed in water for 1 day and then thermocycled. The strength at which the
      bond failed under shear was recorded. RESULTS: None of the surface treatments
      significantly improved the bond strength of Kooliner. Triad bonding agent and
      denture base monomer applications most significantly improved the bond strengths
      of Triad and GC reline, respectively. CONCLUSION: Triad bonding agent and denture
      base monomer should be used in conjunction with Triad and GC reline,
      respectively, when relining a denture base resin.

PMID- 12066700
TI  - A longitudinal study on mandibular implants supporting an overdenture: the
      influence of retention mechanism and anatomic-prosthetic variables on periimplant
      parameters.
AB  - PURPOSE: The aim of this 5-year longitudinal study was to investigate the
      influence of the retention mechanism for overdenture fixation on the periimplant
      parameters of mandibular implants. MATERIALS AND METHODS: Ninety edentulous
      patients, each with two interforaminal implants supporting an overdenture,
      participated in the study. They had received either a straight or slightly bent
      round clip bar, a U-shaped rigid bar with or without distal extensions, or single
      ball anchors. Anatomic-morphologic and prosthetic variables were assessed related
      to the implant position and the type of overdenture retention. The degree of
      mandibular atrophy was determined using cephalometric radiographs. The angle beta
      between the virtual axis connecting both implants and the mandibular hinge axis
      was measured on mounted casts. A supporting surface was identified between bent
      clip bars and U-shaped extension bars. Clinical periimplant parameters were
      recorded, and changes of the probing attachment level after 5 years were analyzed
      in 70 patients with respect to the retention device and anatomic-morphologic and
      prosthetic variables. RESULTS: A significant increase of the Plaque Index was
      observed after 5 years. The mean clinical attachment loss after 5 years was about
      0.2 mm. In more than 50%, beta was small, i.e., < or = 5 degrees. For these
      implants, loss of clinical attachment was significantly lower. The correlation
      between attachment loss and beta was weak, while no significant correlation was
      found with regard to the degree of atrophy and surface. CONCLUSION: In view of
      the long observation period, it was concluded that the position and retention
      mechanism of mandibular implants supporting an overdenture have little influence
      on the long-term stability of the clinical parameters.

PMID- 12066702
TI  - Influence of occlusal factors on treatment outcome: a study of 109 consecutive
      patients with mandibular implant-supported fixed prostheses opposing maxillary
      complete dentures.
AB  - PURPOSE: This study was undertaken to investigate the relationship between
      occlusal variables and clinical and radiologic findings as well as patient
      response to treatment outcome in patients with mandibular implant-supported fixed
      prostheses opposing maxillary complete dentures. MATERIALS AND METHODS: The study
      group consisted of 109 consecutive patients attending for annual control. They
      had received their mandibular implant-supported prostheses according to the
      Branemark system on average 8 years previously (range 1 to 27 years). All
      patients were interviewed with standardized questions by one examiner, who also
      performed the clinical examination. The questions focused on the patients'
      opinion on masticatory and prosthetic function and problems. The clinical
      examination comprised occlusal and prosthetic factors and the health of the oral
      mucosa. RESULTS: The great majority of the patients were very satisfied with
      their present dental situation and masticatory function. Two thirds reported no
      problems with their maxillary complete dentures at all. Balanced occlusion was
      found bilaterally in 61%, and a further 4% had balanced function on one side.
      More than one third thus lacked balanced occlusion. Only about 60% had optimal
      occlusion, and 8% had poor occlusion according to common prosthodontic criteria.
      This was interpreted as a continuing impairment of the occlusion with time. The
      mean bone loss was 0.5 mm, according to available radiographs, for a mean
      observation period of 54 months. There were no or only weak correlations between
      the variables examined. CONCLUSION: The occlusal factors registered were of
      limited importance for patient satisfaction and treatment outcome recorded
      clinically and radiographically at follow-up examination of the actual
      prosthodontic rehabilitation.

PMID- 12066701
TI  - Efficacy of a self-curing adhesive-resin cement system on luting glass-fiber
      posts into root canals: an SEM investigation.
AB  - PURPOSE: The aim of this study was to evaluate the efficacy of a new bonding
      luting system in resin tag, adhesive lateral branch, and hybrid layer formation
      when used in combination with an experimental fiber post. MATERIALS AND METHODS:
      Thirty anterior teeth extracted for periodontal reasons were selected for this
      study. They were endodontically treated and randomly divided into three groups of
      10 samples each: group 1 = Excite light-cured bonding agent in combination with
      Variolink II resin cement; group 2 = Excite dual-cured bonding agent self
      activated by an experimental microbrush in combination with MultiLink resin
      cement; and group 3 = one-step bonding system in combination with Dual Link resin
      cement. In groups 1 and 3, the primer-adhesive solution was light cured before
      placing the resin cement and the post, whereas in group 2 the adhesive/luting
      materials were not light cured. Twenty FRC Postec translucent posts (groups 1 and
      2) and 10 EndoAesthetic translucent fiber posts (group 3) were used. One week
      later, the root samples were processed for scanning electron microscopic (SEM)
      observations. RESULTS: Microscopic examinations of restored interfaces from group
      2 revealed a resin-dentin interdiffusion zone higher than that seen in samples
      from groups 1 and 3 (P < .05). At the apical and middle thirds, the samples from
      group 2 showed significantly more resin tags than the other two groups.
      CONCLUSION: The dual-cure self-activating system showed a more uniform resin tag
      and resin-dentin interdiffusion zone formation along root canal walls than light
      curing systems.

PMID- 12066704
TI  - Preconditions for estimation of masticatory forces from dynamic EMG and isometric
      bite force-activity relations of elevator muscles.
AB  - PURPOSE: Previous studies proposed to estimate masticatory forces from
      electromyograms (EMG) by substituting chewing activities of a particular muscle
      into bite force-activity relations obtained from isometric clenching. For
      biomechanical reasons, this method requires that ratios between muscle forces in
      chewing be the same as in clenching. The purpose of this study was to investigate
      whether this assumption is valid. MATERIALS AND METHODS: In 32 asymptomatic
      subjects, EMGs of bilateral temporal and masseter muscles were registered in
      unilateral clenching on a bite fork and in chewing. Ratios of peak activities of
      different muscles were compared between the two biting tasks. RESULTS: In
      clenching, the working: balancing ratio of the masseters amounted to 0.92, while
      in chewing this ratio increased to 1.9. The working:balancing ratio of the
      temporalis was 1.8 in clenching and dropped to 1.3 in chewing. The
      temporalis:masseter ratio on the balancing side increased from 0.65 in clenching
      to 1.1 in chewing. CONCLUSION: The finding that ratios of muscle activities in
      chewing differed from corresponding ratios in clenching implies different
      combinations of muscle forces and/or different bite force-activity relations in
      the two biting tasks. In any of these cases, prediction of chewing force from the
      EMG of a particular muscle could lead to indefinite overestimations.

PMID- 12066703
TI  - In vitro evaluation of fluoride-releasing restorative materials for sealing the
      root canals of overdenture abutments.
AB  - PURPOSE: The purpose of this study was to evaluate the ability of newer fluoride
      releasing restorative materials to protect the root surface from acid attack.
      MATERIALS AND METHODS: The materials used were glass-ionomer cement (GIC), resin
      modified glass-ionomer cement (RM-GIC), and a compomer (Comp). A composite resin
      (CR) was used as the control. The restored teeth were stored in deionized,
      distilled water for 14 days and subjected to 300 thermocycles (55 degrees C and 5
      degrees C). The teeth were cycled in a demineralizing solution (pH 5.0 or 4.0)
      for 6 hours and in a remineralizing solution (pH 7.0) for 17 hours for 10 days.
      The depths of lesions created by acid challenge were measured at the interface of
      the tooth and the restorative material and then at a distance of 50, 100, and 300
      microns from the tooth-restoration margin using polarized light microscopy and
      contact microradiography. RESULTS: At pH 4.0, there was significant difference in
      the depth at the interface between the tooth and the restorative material (P <
      .001). The GIC and RM-GIC were protective, and the lesion depths were
      significantly shallower than for Comp or CR. The protective effect varied
      depending on the distance from the interface of the tooth and the restorative
      material. At pH 5.0, the GIC and RM-GIC had no lesions at the interface, while
      the Comp and the CR had lesions (P < .001). CONCLUSION: Fluoride-releasing glass
      ionomer cement seems to be an appropriate material to seal the root canals of
      overdenture abutments, because it has an inhibiting effect on demineralization at
      the cavity wall in vitro.

PMID- 12066705
TI  - A method aimed at achieving passive fit in implant prostheses: case report.
AB  - PURPOSE: The aim of this article is to describe a technique that attempts to
      solve titanium-related problems while affording passive fit. MATERIALS AND
      METHODS: The method basically involves the manufacture of a cast titanium
      framework fitted onto titanium machined abutments. After verifying the passive
      fit of the framework presoldered to the abutments, Nd-YAG laser welding is
      completed in the laboratory. RESULTS: The aim of the technique is to secure the
      following clinical benefits: (1) use of titanium, as it is the best-suited
      material; (2) use of high-precision machined abutments; (3) laser welding and its
      advantages; and (4) achievement of passive fit. CONCLUSION: The technique
      described is adequate to achieve passive fit in implant prostheses using titanium
      and laser welding.

PMID- 12066706
TI  - Tooth- and implant-supported prostheses: a retrospective clinical follow-up up to
      8 years.
AB  - PURPOSE: The purpose of this study was to evaluate clinical treatment outcome of
      fixed prostheses in different sizes and with combinations of different numbers of
      teeth and implants as abutments. MATERIALS AND METHODS: A total of 115 implants
      were placed in 36 patients, 75 (65%) in the maxilla and 40 (35%) in the mandible.
      The implants were connected to 85 abutment teeth, 50 in the maxilla and 35 in the
      mandible. Of the prosthetic restorations, 19 were gold ceramic, 17 were gold
      acrylic, three were titanium acrylic, one was titanium ceramic, and one was
      titanium composite. The observation period ranged from 14 months to 8.9 years.
      The treatments comprised both fixed partial dentures supported by one tooth and
      one implant as well as complete-arch fixed prostheses supported by a number of
      teeth and implants. RESULTS: A total of nine implants were lost, three during
      healing and six after loading. The postloading cumulative implant survival rate
      was 89.8% after 5 years. Five abutment teeth were lost, and of the 41 prostheses
      included in the study, only two (5%) were lost during the observation period.
      Marginal bone loss was registered around 46 implants at the 1-year follow-up
      examination. During the following observation period, only slight changes in the
      marginal bone level adjacent to the implants and teeth were registered. The
      magnitude of technical complications was low. CONCLUSION: This investigation
      confirms the findings in similar studies that treatments with periodontally
      healthy teeth and implants splinted together in rigid one-piece superstructures
      show excellent long-term follow-up results.

PMID- 12066708
TI  - Maximum likelihood analysis of gene-based and structure-based process partitions,
      using mammalian mitochondrial genomes.
AB  - Aligned protein-coding genes from 19 completely sequenced mammalian mitochondrial
      genomes were examined by parsimony and maximum likelihood analyses. Particular
      attention is given to a comparison between gene-based and structure-based data
      partitions. Because actual structures are not known for most of the
      mitochondrially encoded proteins, three different surrogate partitioning schemes
      were examined, each based on the identity of the consensus amino acid at a
      specific homologous position. One of the amino-acid-based partitioning schemes
      gave the highest likelihood, but that scheme was based on concordance with a well
      corroborated phylogeny from an earlier parsimony analysis. The gene-based
      partitioning scheme gave a significantly higher likelihood compared to the only
      structure-based scheme examined that could be generated without prior assumptions
      about the phylogeny. Two contrasting phylogenetic inferences were supported by
      the analyses. Both unpartitioned analyses and analyses in which all partitions
      were constrained to have identical patterns of branch lengths supported
      ((Artiodactyla, Cetacea) (Perissodactyla, Carnivora)), whereas all analyses with
      that constraint relaxed supported (((Artiodactyla, Cetacea) Carnivora)
      Perissodactyla).

PMID- 12066707
TI  - Combined molecular phylogenetic analysis of the Orthoptera (Arthropoda, Insecta)
      and implications for their higher systematics.
AB  - A phylogenetic analysis of mitochondrial and nuclear rDNA sequences from species
      of all the superfamilies of the insect order Orthoptera (grasshoppers, crickets,
      and relatives) confirmed that although mitochondrial sequences provided good
      resolution of the youngest superfamilies, nuclear rDNA sequences were necessary
      to separate the basal groups. To try to reconcile these data sets into a single,
      fully resolved orthopteran phylogeny, we adopted consensus and combined data
      strategies. The consensus analysis produced a partially resolved tree that lacked
      several well-supported features of the individual analyses. However, this lack of
      resolution was explained by an examination of resampled data sets, which
      identified the likely source of error as the relatively short length of the
      individual mitochondrial data partitions. In a subsequent comparison in which the
      mitochondrial sequences were initially combined, we observed less conflict. We
      then used two approaches to examine the validity of combining all of the data in
      a single analysis: comparative analysis of trees recovered from resampled data
      sets, and the application of a randomization test. Because the results did not
      point to significant levels of heterogeneity in phylogenetic signal between the
      mitochondrial and nuclear data sets, we therefore proceeded with a combined
      analysis. Reconstructing phylogenies under the minimum evolution and maximum
      likelihood optimality criteria, we examined monophyly of the major orthopteran
      groups, using nonparametric and parametric bootstrap analysis and Kishino
      Hasegawa tests. Our analysis suggests that phylogeny reconstruction under the
      maximum likelihood criteria is the most discriminating approach for the combined
      sequences. The results indicate, moreover, that the caeliferan Pneumoroidea and
      Pamphagoidea, as previously suggested, are polyphyletic. The Acridoidea is
      redefined to include all pamphagoid families other than the Pyrgomorphidae, which
      we propose should be accorded superfamily status.

PMID- 12066709
TI  - Type I error and the power of the s-test: old lessons from a new, analytically
      justified statistical test for phylogenies.
AB  - We present a new procedure for assessing the statistical significance of the most
      likely unrooted dichotomous topology inferrable from four DNA sequences. The
      procedure calculates directly a P-value for the support given to this topology by
      the informative sites congruent with it, assuming the most likely star topology
      as the null hypothesis. Informative sites are crucial in the determination of the
      maximum likelihood dichotomous topology and are therefore an obvious target for a
      statistical test of phylogenies. Our P-value is the probability of producing
      through parallel substitutions on the branches of the star topology at least as
      much support as that given to the maximum likelihood dichotomous topology by the
      aforementioned informative sites, for any of the three possible dichotomous
      topologies. The degree of statistical significance is simply the complement of
      this P-value. Ours is therefore an a posteriori testing approach, in which no
      dichotomous topology is specified in advance. We implement the test for the case
      in which all sites behave identically and the substitution model has a single
      parameter. Under these conditions, the P-value can be easily calculated on the
      basis of the probabilities of change on the branches of the most likely star
      topology, because under these assumptions, each site can become informative
      independently from every other site; accordingly, the total number of informative
      sites of each kind is binomially distributed. We explore the test's type I error
      by applying it to data produced in star topologies having all branches equally
      long, or having two short and two long branches, and various degrees of
      homoplasy. The test is conservative but we demonstrate, by means of a
      discreteness correction and progressively assumption-free calculations of the P
      values, that (1) the conservativeness is mostly due to the discrete nature of
      informative sites and (2) the P-values calculated empirically are moreover mostly
      quite accurate in absolute terms. Applying the test to data produced in
      dichotomous topologies with increasing internal branch length shows that, despite
      the test's "conservativeness," its power is much higher than that of the
      bootstrap, especially when the relevant informative sites are few.

PMID- 12066710
TI  - Effect of nonindependent substitution on phylogenetic accuracy.
AB  - All current phylogenetic methods assume that DNA substitutions are independent
      among sites. However, ample empirical evidence suggests that the process of
      substitution is not independent but is, in fact, temporally and spatially
      correlated. The robustness of several commonly used phylogenetic methods to the
      assumption of independent substitution is examined. A compound Poisson process is
      used to model DNA substitution. This model assumes that substitution events are
      Poisson-distributed in time and that the number of substitutions associated with
      each event is geometrically distributed. The asymptotic properties of
      phylogenetic methods do not appear to change under a compound Poisson process of
      DNA substitution. Moreover, the rank order of the performance of different
      methods does not change. However, all phylogenetic methods become less efficient
      when substitution follows a compound Poisson process.

PMID- 12066711
TI  - Definitions in phylogenetic taxonomy: critique and rationale.
AB  - A general rationale for the formulation and placement of taxonomic definitions in
      phylogenetic taxonomy is proposed, and commonly used terms such as "crown taxon"
      or "node-based definition" are more precisely defined. In the formulation of
      phylogenetic definitions, nested reference taxa stabilize taxonomic content. A
      definitional configuration termed a node-stem triplet also stabilizes the
      relationship between the trio of taxa at a branchpoint, in the face of local
      change in phylogenetic relationships or addition/deletion of taxa. Crown-total
      taxonomies use survivorship as a criterion for placement of node-stem triplets
      within a taxonomic hierarchy. Diversity, morphology, and tradition also
      constitute heuristic criteria for placement of node-stem triplets.

PMID- 12066712
TI  - Charles Darwin's views of classification in theory and practice.
AB  - It has long been argued that Charles Darwin was the founder of the school of
      "evolutionary taxonomy" of the Modern Synthesis and, accordingly, that he
      recognized genealogy and similarity as dual, synergistic criteria for
      classification. This view is based on three questionable interpretations: first,
      of isolated passages in the 13th chapter of the Origin of Species; second, of one
      phrase in a letter that Darwin wrote about the work of an author he had partly
      misunderstood; and third, of his taxonomic practice in the barnacle monographs,
      which only implicitly embody his philosophy of classification, if at all. These
      works, seen in fuller context and with the perspective of extensive
      correspondence, are consistent with the view that Darwin advocated only genealogy
      as the basis of classification, and that similarity was merely a tool for
      discovering evolutionary relationships. Darwin was neither a Mayrian taxonomist
      nor a cladist, and he did not approach systematic issues in the same terms that
      we do in the late 20th century.

PMID- 12066713
TI  - Coding polymorphism for phylogeny reconstruction.
AB  - The methodology of coding polymorphic taxa has received limited attention to
      date. A search of the taxonomic literature revealed seven types of coding
      methods. Apart from ignoring polymorphic characters (sometimes called the fixed
      only method), two main categories can be distinguished: methods that identify the
      start of a new character state with the origin of an evolutionary novelty, and
      methods that identify the new state with the fixation of a novelty. The methods
      of the first category introduce soft reversals, yielding signals that support
      cladograms incompatible with true phylogenies. We conclude that coding the
      plesiomorphy is the method to be preferred, unless the ancestral state is
      unknown, in which case coding as ambiguous is recommended. This holds for coding
      polymorphism in species as well as in supraspecific taxa. In this light we remark
      on methods proposed by previous authors.

PMID- 12066714
TI  - Discriminating and locating character covariance: an application of permutation
      tail probability (PTP) analyses.
AB  - The ability of permutation tail probability (PTP) analyses to discriminate
      between character covariance and noise is investigated with both hypothetical and
      published data sets. PTP is shown to be a powerful tool, not only for detecting
      character covariance, but also for locating that covariance on trees. PTP is
      especially useful for evaluating DNA sequence data that may have a high level of
      homoplasy. A three-step PTP procedure for locating covaried characters is
      presented.

PMID- 12066715
TI  - Is the rate of molecular evolution inversely related to body size?

PMID- 12066716
TI  - Apomorphy distribution is an important aspect of cladogram symmetry.

PMID- 12066717
TI  - Reconciling kingdoms with codes of nomenclature: is it necessary?

PMID- 12066718
TI  - Heparin resistance.

PMID- 12066719
TI  - Haemodilution enhances coagulation.

PMID- 12066720
TI  - 'Ventilating in recovery'--the way forward: intensive therapy or postoperative
      critical care?

PMID- 12066721
TI  - In vivo effect of haemodilution with saline on coagulation: a randomized
      controlled trial.
AB  - BACKGROUND: Previous studies have shown that 10-30% haemodilution with
      crystalloid may induce a hypercoagulable state demonstrable by using the
      Thrombelastograph (TEG). While most are in vitro studies, the few in vivo studies
      are limited by confounding surgical or 'environmental' factors. We conducted this
      randomized controlled study to evaluate the coagulation changes associated with
      in vivo haemodilution. METHODS: Twenty patients undergoing major hepatobiliary
      surgery were randomly allocated to one of two study groups. Group H (n = 10) had
      30% blood volume withdrawn over 30 min and replaced with saline. Group C (n = 10)
      did not have any blood withdrawn. Blood samples were taken in both groups at 10,
      20 and 30 min. Native TEG, complete blood count, coagulation profile, fibrinogen,
      antithrombin III, protein C and thrombin-antithrombin complex concentrations were
      measured. RESULTS: Compared with Group C, Group H patients had significantly
      greater shortening of r-time at 30 min (-30% vs +36%), greater shortening of k
      time at all time points (-36% vs +17% at 10 min; -37% vs +44% at 20 min; -45% vs
      +49% at 30 min), and greater widening of alpha at 30 min (+71% vs +4%). The
      decrease in antithrombin III and other natural procoagulants and anticoagulants
      closely followed that of haematocrit, with the exception of thrombin-antithrombin
      complex. CONCLUSION: In vivo haemodilution of up to 30% with saline can induce a
      hypercoagulable state. The mechanism remains unclear as disproportionate dilution
      of natural anticoagulants was not detected. Thrombin-antithrombin complex
      concentration remained stable despite haemodilution in Group H, which may suggest
      increased thrombin generation.

PMID- 12066723
TI  - Glucose, insulin and potassium for heart protection during cardiac surgery.
AB  - BACKGROUND: Coronary artery bypass grafting with hypothermic cardiac arrest and
      cardiopulmonary bypass (CPB) is associated with myocardial injury. Our study
      investigated whether an infusion of glucose, insulin and potassium (GIK) during
      elective coronary artery bypass surgery decreases myocardial cell death. METHODS:
      We measured cardiac troponin I (cTnI), a myofibrillar structural protein, which
      is a sensitive and specific indicator of myocytic injury. With ethics committee
      approval, 42 patients were enrolled into a randomized, prospective, double
      blinded study. In the GIK group, 500 ml of 50% dextrose solution containing 100
      IU insulin and potassium 80 mmol was infused at the rate of 0.75 ml kg(-1) h(-1).
      Patients in the non-GIK group received 5% dextrose solution at the same rate.
      Arterial blood samples were taken before induction of anaesthesia, after removal
      of the aortic clamp and 6 and 12 h after CPB. RESULTS: In both groups there was
      an increase in cTnI concentration (P<0.05), which was greatest about 6 h after
      CPB. At no time did the cTnI concentration differ between the two groups.
      CONCLUSION: The results suggest that GIK does not decrease the irreversible
      myocardial damage associated with routine coronary artery bypass surgery.

PMID- 12066722
TI  - Can a clinically useful aortic pressure wave be derived from a radial pressure
      wave?
AB  - BACKGROUND: The information contained in arterial pressure waveforms is probably
      underused by most clinicians who manage critically ill patients. It is not
      generally known that an aortic pressure wave can be synthesized by applying a
      generalized transfer function to the radial arterial pressure wave. We validated
      a commercially available system, SphygmoCo (PWV Medical, Sydney). METHODS:
      Ascending aortic pressure waves were synthesized and comparisons were made
      between the synthesized aortic waveforms, the measured aortic and radial arterial
      waveforms. Ascending aortic pressure waves (catheter-tip manometer) and radial
      artery pressure waves (short fluid-filled catheter) were recorded simultaneously
      in 12 patients with angina pectoris (age 62-76 years) undergoing cardiac
      catheterization. Patients were studied at rest, following midazolam, sublingual
      nitroglycerin and during Valsalva manoeuvres. RESULTS: Both midazolam and
      nitroglycerin lowered mean arterial pressure but nitroglycerin caused a more
      selective decrease in the measured and synthesized aortic systolic pressures than
      in the radial artery pressure. The synthesized aortic systolic pressure was less,
      by 6-8 mm Hg (SD 2-3) and the synthesized aortic diastolic pressure greater, by 4
      mm Hg (SD 2). Despite these differences in pulse pressure, the synthesized
      waveform tracked the measured waveform before and during interventions.
      CONCLUSIONS: By deriving an aortic waveform from the radial pulse, monitoring of
      left ventricular afterload can improve without more invasive means.

PMID- 12066724
TI  - Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during
      cardiac surgery.
AB  - BACKGROUND: Cytokines regulate inflammation associated with cardiopulmonary
      bypass (CPB). Pro-inflammatory cytokines may cause myocardial dysfunction and
      haemodynamic instability after CPB, but the release of anti-inflammatory
      cytokines is potentially protective. We studied the effects of dexamethasone on
      pro- and anti-inflammatory cytokine responses during coronary artery bypass
      grafting surgery. METHODS: Seventeen patients were studied: nine patients
      received dexamethasone 100 mg before induction of anaesthesia (group 1) and eight
      patients acted as controls (group 2). Plasma levels of tumour necrosis factor
      (TNF)-alpha, interleukin (IL)-6, IL-8, IL-10 and IL-4 were measured
      perioperatively. RESULTS: TNF-alpha and IL-8 did not increase significantly in
      group 1 whereas they increased in group 2 to greater than preoperative values
      (P<0.05). IL-6 increased in both groups, with lower values in group 1 than in
      group 2 (P<0.05). IL-10 increased in both groups, with higher values in group 1
      (P<0.05). IL-4 did not change in group 1 but decreased in group 2 compared with
      pre-induction values (P<0.05). After surgery, patients in group 2 had
      tachycardia, hyperthermia, a greater respiratory rate and higher pulmonary artery
      pressure, and a longer stay in the intensive care unit. CONCLUSION: Dexamethasone
      given before cardiac surgery changes circulating cytokines in an anti
      inflammatory direction. Postoperative outcome may be improved by inhibition of
      the systemic inflammatory response.

PMID- 12066725
TI  - Effect of sevoflurane/nitrous oxide versus propofol anaesthesia on somatosensory
      evoked potential monitoring of the spinal cord during surgery to correct
      scoliosis.
AB  - BACKGROUND: Use of intraoperative somatosensory evoked potential (SSEP)
      monitoring is helpful in spinal corrective surgery but may be affected by
      anaesthetic drugs. An anaesthetic technique that has less effect on SSEP or
      allows faster recovery is an advantage. We compared the effects on SSEP and the
      clinical recovery profiles of sevoflurane/nitrous oxide and propofol anaesthesia
      during surgery to correct scoliosis. METHODS: Twenty adolescent patients were
      randomized into two groups of 10. One group received sevoflurane-nitrous oxide
      anaesthesia and the other received propofol i.v. anaesthesia. An alfentanil
      infusion was used for analgesia in both groups. RESULTS: Changes in anaesthetic
      concentration produced little effect on the latency of SSEP, but the effect on
      the variability of SSEP amplitude was significant (P<0.05). Sevoflurane produced
      a faster decrease in SSEP and a faster recovery than propofol (P<0.05). On
      emergence, patients who received sevoflurane tended to have shorter recovery
      times to eye opening (mean 5.1 vs 20.6 min, P=0.09) and toe movement (mean 7.9 vs
      15.7 min, P=0.22). Those who had received sevoflurane were significantly more
      lucid and cooperative in recovery. CONCLUSIONS: Sevoflurane produces a faster
      decrease and recovery of SSEP amplitude as well as a better conscious state on
      emergence than propofol.

PMID- 12066726
TI  - Malignant hyperthermia associated with exercise-induced rhabdomyolysis or
      congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian
      pedigrees.
AB  - Malignant hyperthermia (MH) is rarely associated with specific myopathies or
      musculoskeletal abnormalities. Three clinical investigations of MH associated
      with either non-specific myopathies or congenital disorders in three separate
      families are presented. Two of these cases also show evidence of exercise-induced
      rhabdomyolysis. In each case MH susceptibility was confirmed by in vitro
      contracture testing of quadriceps muscle. DNA sequence analysis of each kindred
      revealed the presence of a common novel mutation that results in an arginine401
      cysteine substitution in the skeletal muscle ryanodine receptor gene (RYR1).
      Haplotype analysis using chromosome 19q markers indicated that the three families
      are likely to be unrelated, providing confirmation that the MH/central core
      disease region 1 of RYR1 is a mutation hot spot.

PMID- 12066727
TI  - Comparison of mepivacaine and lidocaine for intravenous regional anaesthesia:
      pharmacokinetic study and clinical correlation.
AB  - BACKGROUND: Limitations to the use of lidocaine for intravenous regional
      anaesthesia (IVRA) include lack of optimal intraoperative analgesia and systemic
      toxic reactions. This randomized double-blind study was conducted to compare
      intraoperative and postoperative analgesia, adverse effects, and plasma
      concentrations of mepivacaine or lidocaine, on release of the tourniquet in
      patients undergoing IVRA for distal upper limb surgery. METHODS: Forty-two adult
      patients were randomly allocated to receive either a 0.5% lidocaine solution 3 mg
      kg(-1) (n=20) or mepivacaine 5 mg kg(-1) (n=22). Plasma concentrations of both
      anaesthetic agents were measured at 5, 10, 20, 30, 45, and 60 min after deflation
      of the tourniquet by gas chromatography. RESULTS: Although plasma concentrations
      of mepivacaine and lidocaine were comparable 5 min after deflation,
      concentrations of lidocaine decreased significantly thereafter, whereas plasma
      concentrations of mepivacaine were similar over the 60-min study period.
      Supplementary analgesia during the intraoperative period was required by 45% of
      patients in the lidocaine group as compared with 9% in the mepivacaine group
      (P=0.02). No adverse effects were observed in patients given mepivacaine. In the
      lidocaine group, adverse effects were observed in 10% of the patients. The total
      ischaemia time, volume of the local anaesthetic, and duration of the surgical
      procedure were not significantly different between the two groups. CONCLUSIONS:
      Mepivacaine 5 mg kg(-1) ensured better intraoperative analgesia than lidocaine 3
      mg kg(-1) when used for IVRA. Plasma concentrations of lidocaine decreased
      significantly between 5 and 60 min following tourniquet deflation, whereas blood
      concentrations of mepivacaine remained below the toxic concentration.

PMID- 12066728
TI  - Effect of perioperative administration of dexketoprofen on opioid requirements
      and inflammatory response following elective hip arthroplasty.
AB  - BACKGROUND: In this double-blind, randomized, placebo-controlled trial, the
      safety and analgesic efficacy of perioperative dexketoprofen were evaluated.
      METHODS: Thirty ASA I or II patients undergoing elective hip arthroplasty were
      randomized to one of two groups. One group (D) received dexketoprofen 25 mg tds
      for 24 h before and 48 h after surgery; the second group (P) received placebo
      tablets at equivalent times. Hyperbaric 0.5% bupivacaine (17.5 mg if greater than
      70 kg and 15 mg if less than 70 kg) and preservative-free morphine (0.6 mg) were
      administered intrathecally. Postoperatively, PCA was provided (bolus morphine
      sulphate 1 mg; lockout 5 min; no continuous infusion). RESULTS: The two groups
      were similar in terms of age, gender, weight, height, ASA class, duration of
      operation, and level of sensory block on arrival to the recovery room. Groups
      were also similar in terms of blood loss, transfusion requirements, ventilatory
      frequency, and haemodynamic variables. According to visual analogue pain scores
      patients in group D experienced less pain at 15 h (P=0.02) postoperatively.
      Cumulative morphine consumption was also less in group D compared with group P at
      6 (0.06 (0.2) vs 0.85 (1.4) mg, P=0.04) and 48 h postoperatively (10.1 (8) vs
      26.2 (20) mg, P<0.01). Plasma interleukin 6 concentrations increased
      postoperatively to a significantly lesser extent in group D than in group P
      (P=0.02). Nausea and vomiting were less (P<0.01) in group D compared with group P
      at 18 h postoperatively. Sedation scores were less (P=0.03) in group D.
      CONCLUSIONS: Perioperative administration of dexketoprofen 25 mg 8 hourly
      markedly improves analgesia and decreases opioid requirements (and associated
      adverse effects) following hip arthroplasty. It appears that this regimen
      decreases the postoperative pro-inflammatory response.

PMID- 12066729
TI  - Randomized crossover comparison of the proseal with the classic laryngeal mask
      airway in unparalysed anaesthetized patients.
AB  - BACKGROUND: The ProSeal is a wire-reinforced laryngeal mask airway with an
      additional drain tube that leads to the distal tip of the laryngeal cuff. The
      design should improve the seal with the larynx. METHODS: The ProSeal and classic
      laryngeal mask airways were compared in 180 patients in a randomized crossover
      study. Patients were anaesthetized without neuromuscular blocking drugs. RESULTS:
      The ProSeal took more time and more attempts to insert successfully than the
      classic laryngeal mask airway. Insertion was successful on the first attempt in
      81% of cases with the ProSeal and 90% with the classic laryngeal mask airway. The
      ProSeal required more air to achieve an intracuff pressure of 60 cm H2O (6 ml
      more for size 4 and 12 ml more for size 5). Laryngeal seal pressure was better
      with the ProSeal than the classic laryngeal mask airway. Median seal pressure was
      29 cm H2O with the ProSeal and 18 cm H2O with the classic laryngeal mask airway.
      Laryngeal seal pressure was greater than 20 cm H2O in 87% of patients with the
      ProSeal and 41% with the classic laryngeal mask airway. Laryngeal seal pressure
      was greater than 40 cm H2O in 21% of patients with the ProSeal and in none of the
      patients with the classic laryngeal mask. Once placed, the ProSeal remained a
      stable and effective airway. Gastric tube insertion through the drain tube was
      attempted in 147 cases and was successful in 135 (92%). CONCLUSION: The ProSeal
      is more difficult to insert than the classic laryngeal mask airway but allows
      positive pressure ventilation more reliably than the classic laryngeal mask
      airway.

PMID- 12066730
TI  - The proseal laryngeal mask: results of a descriptive trial with experience of 300
      cases.
AB  - BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is a new laryngeal mask
      device with a modified cuff and a drainage tube. METHODS: We assessed the PLMA in
      300 anaesthetized adults either paralysed or breathing spontaneously. We assessed
      insertion characteristics, airway seal pressures, haemodynamic response to
      insertion, ease of gastric tube placement, gastric insufflation, and
      postoperative sore throat. RESULTS: Insertion was successful in 294 patients
      (98%) and graded as easy in 274 patients (91%). We found no difference in ease of
      insertion or success rate with either the introducer or the finger insertion
      method, or in paralysed or non-paralysed patients. Mean airway seal pressure was
      29 cm H2O, and 59 patients (20%) had seal pressures greater than 40 cm H2O. No
      gastric insufflation was detected. Gastric tube placement was successful in 290
      of 294 patients (98.6%). There was no cardiovascular response to insertion, with
      a small reduction in heart rate 5 min after insertion and significant decreases
      in mean arterial pressure at 1 and 5 min after insertion. Sore throat was noted
      in 23% patients after operation and in 16% of patients after 24 h, with 90% of
      the sore throats described as mild. CONCLUSIONS: The PLMA is a reliable airway
      management device that can give an effective glottic seal in paralysed and non
      paralysed patients. The device allows the easy passage of a gastric tube, causes
      a minimal haemodynamic response to insertion, and an acceptable incidence of sore
      throat.

PMID- 12066731
TI  - Increased airway resistance during xenon anaesthesia in pigs is attributed to
      physical properties of the gas.
AB  - BACKGROUND: In this study we investigated the effects of the physical properties
      of xenon on respiratory mechanisms in pigs. METHODS: With institutional approval,
      10 female pigs (mean 25.2 (SD 2.5) kg) were anaesthetized with thiopental,
      remifentanil, and pancuronium. Gas flow and pressure were recorded continuously
      at the proximal end of the tracheal tube during constant flow ventilation for
      control, with 100% oxygen (control), followed by 1.5% isoflurane in 70/30%
      nitrogen/oxygen, 1.0% isoflurane in 70/30% nitrous oxide/oxygen, and 70/30%
      xenon/oxygen in random order. Compliance (C) and resistance (R) were calculated
      using a single compartment model. Resistance was corrected for gas viscosities
      eta and also for densities pho and viscosities eta as (pho*eta)(1/2) to compare
      assumptions of laminar and mixed flow in the airways. RESULTS: With constant flow
      ventilation, xenon increases inspiratory pressure compared with other gas
      mixtures. There were no significant differences in resistance, corrected for
      laminar or mixed flow, between the gas mixtures. Xenon anaesthesia did not affect
      compliance. CONCLUSIONS: The increase in airway pressure observed with xenon
      anaesthesia is attributed completely to its higher density and viscosity.
      Therefore, determination of airway resistance must take into account the physical
      properties of the gas. Xenon does not exert any major effect on airway diameter.

PMID- 12066732
TI  - Xenon increases total body oxygen consumption during isoflurane anaesthesia in
      dogs.
AB  - BACKGROUND: This study was designed to examine whether the coupling between
      oxygen consumption (VO2) and cardiac output (CO) is maintained during xenon
      anaesthesia. METHODS: We studied the relationship between VO2 (indirect
      calorimetry) and CO (ultrasound flowmetry) by adding xenon to isoflurane
      anaesthesia in five chronically instrumented dogs. Different mixtures of xenon
      (70% and 50%) and isoflurane (0-1.4%) were compared with isoflurane alone (1.4%
      and 2.8%). In addition, the autonomic nervous system was blocked (using
      hexamethonium) to study its influence on VO2 and CO during xenon anaesthesia.
      RESULTS: Mean (SEM) VO2 increased from 3.4 (0.1) ml kg(-1) min(-1) during 1.4%
      isoflurane to 3.7 (0.2) and 4.0 (0.1) ml kg(-1) min(-1) after addition of 70% and
      50% xenon, respectively (P<0.05), whereas CO and arterial pressure remained
      essentially unchanged. In contrast, 2.8% isoflurane reduced both, VO2 [from 3.4
      (0.1) to 3.1 (0.1) ml kg(-1) min(-1)] and CO [from 96 (5) to 70 (3) ml kg(-1)
      min(-1)] (P<0.05). VO2 and CO correlated closely during isoflurane anaesthesia
      alone and also in the presence of xenon (r2=0.94 and 0.97, respectively), but the
      regression lines relating CO to VO2 differed significantly between conditions,
      with the line in the presence of xenon showing a 0.3-0.6 ml kg(-1) min(-1)
      greater VO2 for any given CO. Following ganglionic blockade, 50% and 70% xenon
      elicited a similar increase in VO2, while CO and blood pressure were unchanged.
      CONCLUSIONS: Metabolic regulation of blood flow is maintained during xenon
      anaesthesia, but cardiovascular stability is accompanied by increased VO2. The
      increase in VO2 is independent of the autonomic nervous system and is probably
      caused by direct stimulation of the cellular metabolic rate.

PMID- 12066733
TI  - Does ester hydrolysis change the in vitro degradation rate of cisatracurium and
      atracurium?
AB  - BACKGROUND: We assessed the role of ester hydrolysis as an additional degradation
      mechanism to Hofmann elimination in the breakdown of cisatracurium and
      atracurium. METHODS: Cisatracurium and atracurium were incubated in phosphate
      buffer (pH 7.4, 37 degrees C) with and without the addition of carboxylesterase.
      Control measurements with an added esterase inhibitor were performed separately.
      Cisatracurium/atracurium and their degradation products, laudanosine and
      monoquaternary acid, were analysed using high-pressure liquid chromatography.
      RESULTS: Degradation of cisatracurium and atracurium proceeded exponentially, and
      after addition of carboxylesterase, no significant differences in the degradation
      rates were found. Neither an increase in carboxylesterase activity nor the
      addition of esterase inhibitor showed any effect. However, areas under the peaks
      of the chromatogram representing monoquaternary acid increased during incubation
      with esterase. CONCLUSION: The rate-limiting step in the degradation of
      cisatracurium/atracurium is Hofmann elimination. Ester hydrolysis is involved in
      the second degradation step that forms monoquaternary acid, but its contribution
      to the total elimination rate is negligible.

PMID- 12066734
TI  - Chirality: a blueprint for the future.
AB  - The chirality that is inherent in the enzyme systems of living organisms results
      in an abundance of enantiopure organic molecules in the living world. In addition
      to the optical properties first noticed by Pasteur, stereospecific interactions
      at recognition sites result in differences in both biological and toxicological
      effects. This fact underlies the continuing growth in chiral chemistry, rooted as
      it is in fundamental biochemistry. The pharmaceutical industry has undergone a
      strategic shift and embraced the wide spectrum of asymmetrical synthetic methods
      now available. The use of these processes in developmental synthesis and large
      scale manufacturing has provided new challenges in drug discovery, motivated by a
      desire to improve industrial efficacy and decrease the time from the conception
      of a new drug to the market. The economic impact of the industrial production of
      chiral drugs is now huge--more than 50% of the 500 top-selling drugs were single
      enantiomers in 1997. Sales have continued to increase by more than 20% for the
      past 6 yr and worldwide annual sales of enantiomeric drugs exceeded US$100
      billion for the first time in the year 2000, chiral drugs representing close to
      one-third of all sales worldwide. While some 'chiral switches' may be of less
      apparent benefit, or indeed detrimental in some cases, encouragement by the
      regulatory agencies and the ability to extend the life cycle of a drug coming off
      patent promotes the trend. However, it may turn out to be the ability to provide
      chiral templates, and thereby attack the key targets of selectivity and
      specificity, that will lead to the greatest benefits. Research into new chemical
      entities that can interact specifically with enzyme families may potentially lead
      to new therapies for complex disease processes. As Richards has stated, the
      approach is designed to create a made to measure product, rather than one off the
      peg.

PMID- 12066735
TI  - The postanaesthesia care unit as a temporary admission location due to intensive
      care and ward overflow.
AB  - BACKGROUND: With the increasing number of critically ill patients, and shortage
      of intensive care unit and ward beds, some postoperative patients stay for an
      unnecessarily long period in the postanaesthesia care unit (PACU), until a
      suitable bed is available. METHODS: We prospectively studied this patient
      overflow admission to the PACU over 33 months. Four hundred patients with a mean
      age of 53.1 yr (range 0.2-94) were studied. Two hundred and eighty one (70.3%)
      patients were mechanically ventilated on admission to the PACU and 311 (77.8%)
      had invasive monitoring. Mean length of stay in the PACU was 12.9 (SD 10.6) h.
      RESULTS: The busiest hours of admission were 01-11 am. Eighteen (4.5%) patients
      died in the PACU, while waiting for an intensive care unit bed. The main problems
      were insufficient medical and nursing coverage, and inadequate communication and
      visiting facilities for patient's families. CONCLUSION: Patient overflow to the
      PACU is a common problem that requires attention. Guidelines for medical and
      nursing coverage, patient triage, and communication with relatives need to be
      outlined.

PMID- 12066737
TI  - Postoperative sore throat after ambulatory surgery.
AB  - BACKGROUND: Sore throat is a common complication of anaesthesia that affects
      patient satisfaction after surgery. METHODS: We studied 5264 ambulatory surgical
      patients prospectively to determine the patient, anaesthetic, and surgical
      factors associated with sore throat. RESULTS: In 5264 patients, 12.1% reported a
      sore throat. Patients with tracheal tube had the greatest incidence, 45.4%,
      followed by patients with laryngeal mask airway, 17.5%, while patients with a
      facemask had a lower incidence of sore throat, 3.3%. Female patients had more
      sore throats than male patients (13.4 vs 9.1%). Airway management had the
      strongest influence on the incidence of sore throat. Sore throat in ambulatory
      surgical patients was associated with female sex, younger patients, use of
      succinylcholine, and gynaecological surgery. CONCLUSION: Airway management,
      female sex, younger patients, surgery for gynaecological procedure, and
      succinylcholine predicts postoperative sore throat. Increased awareness of the
      predictive factors can help to avoid this combination and improve patient
      satisfaction.

PMID- 12066736
TI  - Radial artery cannulation: topical amethocaine gel versus lidocaine infiltration.
AB  - BACKGROUND: In a prospective randomized study, we compared topical 4% amethocaine
      gel (Ametop) with 2% lidocaine infiltration for analgesia for radial artery
      cannulation. A previous study had shown topical analgesia with EMLA cream reduced
      pain, shortened cannulation time, and improved success rates when compared with
      lidocaine infiltration. METHODS: One hundred adult patients undergoing elective
      cardiac surgery were randomized. Cannulation times and success rates were
      compared between the two groups. The quality of analgesia was assessed using a
      visual analogue scale (VAS) and four-point verbal pain scoring system. RESULTS:
      Ninety-nine sets of data were analysed using Mann-Whitney U and chi-squared
      tests. Mean time to cannulation was 56 s in the amethocaine group (interquartile
      range (IQR) 41-142) and 59 s in the lidocaine group (IQR 40-105). The median pain
      score on the VAS was 2 in both groups (IQR 1-3.5 for amethocaine and 0-4 for
      lidocaine). CONCLUSIONS: There was no significant difference between these two
      methods of analgesia for any measured variable.

PMID- 12066738
TI  - ProSeal laryngeal mask protects against aspiration of fluid in the pharynx.
AB  - BACKGROUND: The ProSeal laryngeal mask airway (PLMA) is a new device designed to
      isolate the airway from the digestive tract. METHODS: We studied the ability of
      the PLMA to isolate the airway in 103 anaesthetized adults who were breathing
      spontaneously or given neuromuscular blocking agents, by filling the hypopharynx
      with methylene blue-dyed saline introduced down the drainage tube once the mask
      was in place. At the beginning and end of the procedure, a fibre-optic
      bronchoscope was passed down the airway tube to observe any dyed saline in the
      bowl of the mask. RESULTS: The PLMA was positioned correctly in all successful
      attempts (102 out of 103 attempts) and was able to isolate the glottis from fluid
      in the hypopharynx in all patients initially. Leakage of saline into the bowl of
      the mask occurred in two patients in whom displacement of the mask was caused by
      upper airway events during the procedure. In the remaining 100 patients, the
      glottis was isolated successfully for the duration of the procedure. CONCLUSIONS:
      The PLMA can be positioned reliably. It can isolate the airway from fluid in the
      hypopharynx.

PMID- 12066739
TI  - No evidence of mutations in the CACNA1S gene in the UK malignant hyperthermia
      population.
AB  - BACKGROUND: Malignant hyperthermia (MH) is an inherited, potentially fatal,
      pharmocogenetic disorder triggered by certain anaesthetic agents. In light of the
      reported genetic heterogeneity for the disorder and the recent introduction of
      DNA testing guidelines for the trait, we have assessed the role of the CACNA1S
      gene in MH susceptibility in UK patients. Linkage to this locus has previously
      been demonstrated in several European MH families. METHODS AND RESULTS: We
      screened 200 unrelated MH-susceptible individuals for known CACNA1S mutations.
      With the aim to characterize further novel mutations at this locus, functionally
      relevant regions of the gene were also sequenced in 10 unrelated individuals from
      families where the involvement of other MH susceptibility loci was unlikely. No
      sequence variations were detected in any of the patients investigated.
      CONCLUSIONS: Defects in CACNA1S are not a major cause of MH in the UK population.
      Diagnostic screening of this gene is unlikely to be of value to UK MH patients in
      the near future.

PMID- 12066740
TI  - Transoesophageal echocardiographic monitoring of pulmonary venous obstruction
      induced by sternotomy closure during infant heart transplantation.
AB  - A case of an infant receiving orthotopic heart transplantation with over-sized
      donor heart was reported. Left lower pulmonary venous obstruction after
      sternotomy closure was detected by transoesophageal echocardiography (TOE) and
      the decision to delay sternal closure was made and the clinical outcome was very
      satisfactory. The usefulness of intraoperative TOE monitoring and postoperative
      TOE follow-up for infant heart transplantation, especially in those cases of size
      mismatch, was well demonstrated.

PMID- 12066741
TI  - Oesophagotracheal perforation after intraoperative transoesphageal
      echocardiography in cardiac surgery.
AB  - Although transoesophageal echocardiography (TOE) can be considered a safe
      procedure, severe complications may occur. We report an oesophagotracheal
      perforation diagnosed 7 days after a complex and very long four-valve replacement
      procedure in a patient with a poor preoperative condition. We believe that an
      ischaemic lesion of the oesophagotracheal wall caused by the TOE probe was the
      initial event leading to this perforation. This observation raises concerns about
      the safety of prolonged TOE monitoring and suggests that a combination of risk
      factors (i.e. a small stature, a very long procedure, congestive heart failure,
      and a low cardiac output before and after cardiopulmonary bypass) may warrant
      increased precautions while performing TOE during cardiac surgery.

PMID- 12066742
TI  - Late oesophageal perforation after intraoperative transoesophageal
      echocardiography.
AB  - Serious haemodynamic instability occurred during emergency surgery for a
      perforated duodenal ulcer in a 72-year-old man with acute myocardial infarction.
      Intraoperative transoesophageal echocardiography was crucial for diagnosis of the
      location of myocardial infarction in the right ventricle and the subsequent
      haemodynamic management. Postoperatively, a thrombus in the right coronary artery
      was removed by coronary angiography. The patient's trachea was extubated on the
      fourth postoperative day. Another 4 days later a leak in the lower oesophagus was
      suspected because of pleural empyema, and verified. The patient's trachea had to
      be re-intubated and an oesophageal stent was inserted. The patient was
      discharged, fully recovered, 2 months after the operation.

PMID- 12066743
TI  - Oxygen embolism after hydrogen peroxide irrigation of a vulvar abscess.
AB  - We report a case of venous oxygen embolism in a 33-yr-old healthy woman after
      irrigation of a vulvar abscess with 25 ml of 3% hydrogen peroxide. Venous oxygen
      embolism was diagnosed by the development of sudden hypoxia associated with a
      decrease in end-tidal carbon dioxide concentration from 5.3 kPa to 3.2 kPa, and a
      'mill-wheel' sound on cardiac auscultation soon after injection of the solution.
      The patient responded to corrective treatment including the Trendelenburg
      position and 100% oxygen. She made an uneventful recovery. We discuss the
      possible causative mechanism of this embolism, the different diagnostic methods,
      and the controversial aspects of available treatments. We emphasize that hydrogen
      peroxide is a dangerous and unsuitable agent for routine wound irrigation and
      debridement.

PMID- 12066744
TI  - Anaphylaxis to rocuronium.
AB  - Reports about anaphylactic and anaphylactoid reactions to rocuronium have
      increased recently. We report two new cases of documented grade III anaphylaxis,
      leading to death in one patient. The first case occurred in an 81-year-old ASA II
      woman scheduled for emergency abdominal surgery. Severe hypotension and
      tachycardia were observed after rocuronium, without bronchospasm. Neosynephrine
      allowed rapid resuscitation, and the patient recovered fully. The second patient
      was a 64-year-old ASA II man scheduled for abdominal surgery. Severe haemodynamic
      instability and bronchospasm occurred after rocuronium. Despite immediate life
      support, the postoperative period was complicated by persistent low systolic
      pressure, acute respiratory distress syndrome, acute renal failure, disseminated
      intravascular coagulation and pancreatitis, leading to the death of the patient.

PMID- 12066745
TI  - Serotonin toxicity and malignant hyperthermia: role of 5-HT2 receptors.

PMID- 12066746
TI  - Anaphylaxis during anaesthesia.

PMID- 12066747
TI  - Receptive site topology of the acetylcholine receptor.

PMID- 12066748
TI  - The alveolar lining.

PMID- 12066749
TI  - Avoiding airway obstruction.

PMID- 12066750
TI  - Transtracheal high frequency jet ventilation for endolaryngeal surgery.

PMID- 12066751
TI  - Delayed diagnosis of cardiac tamponade.

PMID- 12066752
TI  - Unnecessary Caesarean section due to silent CTG.

PMID- 12066753
TI  - Intrathecal ropivacaine or bupivacaine with fentanyl for labour.

PMID- 12066754
TI  - Combined epidural and general anaesthesia in a patient with a transplanted heart
      undergoing upper abdominal surgery.

PMID- 12066755
TI  - Anaesthesia for cataract surgery.

PMID- 12066757
TI  - New semiautomatic suturing device (Maniceps) for precise vesicourethral
      anastomosis during radical retropubic prostatectomy.

PMID- 12066756
TI  - Use of remifentanil in fast atrial fibrillation.

PMID- 12066758
TI  - Therapeutic products: innovation versus quality.

PMID- 12066759
TI  - The human G protein beta 3 subunit GNB3 825T polymorphism.

PMID- 12066760
TI  - Infections in the elderly: Part 3.
AB  - The number of elderly individuals is rapidly growing. As a result, more emergency
      transports will involve the care of an elderly patient. Distinguishing the cause
      of symptoms can be difficult for healthcare professionals, including emergency
      personnel. Clinical symptoms of infection may be absent, or not as obvious as
      with a younger individual. The aging process of the immune system results in the
      inability to fight off many infections. Transport of patients with antibiotic
      resistant organisms has caused many challenges for emergency care personnel
      surrounding infection control practices.

PMID- 12066761
TI  - Wait watcher. Beware the dead-cat bounce.

PMID- 12066762
TI  - Bed-blocking. Juggling acts. Interview by Alison Moore.

PMID- 12066763
TI  - Redefining the practice of dentistry.

PMID- 12066764
TI  - Biomimetic dental implants--new ways to enhance osseointegration.

PMID- 12066765
TI  - WHO to push for $66 billion investment in health.

PMID- 12066766
TI  - Sugarcane, chicken and radish sprouts: a sampling of country food safety
      experiences.

PMID- 12066767
TI  - Cheilitis granulomatosa: overview of 13 patients with long-term follow-up-
      results of management.
AB  - BACKGROUND: Cheilitis granulomatosa, often regarded as a subtype of orofacial
      granulomatosis, is characterized by recurrent or persistent swelling of one or
      both lips. Classically, a non-necrotizing granulomatous inflammation is seen at
      histologic examination. Although a relationship has been proposed between
      Melkersson-Rosenthal syndrome (and the monosymptomatic form, cheilitis
      granulomatosa) and Crohn's disease on the basis of the orofacial swelling and
      similar histology, several studies of Melkersson-Rosenthal syndrome have not
      found an association with Crohn's disease. METHODS: The clinical features,
      histopathology, association with Crohn's disease, and results of nonsurgical and
      surgical therapy in 13 patients with cheilitis granulomatosa were investigated in
      a retrospective case study with a mean follow-up period of 8.2 years. RESULTS:
      There was a low chance of developing Crohn's disease. Most patients in this study
      responded to nonsurgical treatment modalities. Patients with deterioration of lip
      swelling usually responded to intralesional injections with triamcinolone or to
      short courses of systemic glucocorticoids. Nonsteroidal systemic modalities, such
      as clofazimine, hydroxychloroquine, or sulfasalazine, were alternatives to
      glucocorticoid regimens, thus avoiding the long-term side effects of
      corticosteroids. Surgical intervention should only be performed in severely
      disfiguring cases. CONCLUSIONS: The management of cheilitis granulomatosa remains
      a challenge. As this study revealed a low chance of developing Crohn's disease,
      it does not seem justified to inform patients with cheilitis granulomatosa of the
      possibility that they might develop Crohn's disease. Patients with a negative
      history of gastrointestinal complaints should not be exposed to routine
      investigations of the gastrointestinal tract.

PMID- 12066768
TI  - Re: A critical review of cost reduction in the neonatal intensive care unit.

PMID- 12066769
TI  - Let's not be caught unawares.

PMID- 12066770
TI  - Run your practice--don't let it run you.

PMID- 12066771
TI  - 21st-century dental assistants are knowledge workers.

PMID- 12066773
TI  - The renal tubular handling of aldosterone and its acid-labile conjugate.
AB  - Stop-flow studies using infusions of aldosterone-(3)H or its (3)H acid-labile
      conjugate were done on five rhesus monkeys. The aldosterone-(3)H urine-to-plasma
      (U/P) ratio decreased in the same distal urine samples as sodium. The (3)H acid
      labile conjugate U/P-to-inulin U/P ratio increased in the more proximal samples
      either with conjugate formed endogenously during aldosterone-(3)H infusions or
      with labeled conjugate infused alone. Aldosterone reabsorption occurred at a
      distal site in the renal tubule, and secretion of its acid-labile conjugate
      occurred at a proximal site.

PMID- 12066772
TI  - Turnover of plasma cholesterol in man.
AB  - Cholesterol-4-(14)C was injected intravenously into a series of normal men,
      untreated hyperlipidemic patients, and hyperlipidemic patients being treated with
      cholestyramine. The specific radioactivity of plasma total cholesterol was
      measured during the ensuing 10 wk. 16 studies were carried out in 10 subjects.
      Analysis of the turnover curves of plasma cholesterol revealed that in every
      study the turnover of plasma cholesterol conformed to a two-pool model. Each
      turnover curve was analyzed in terms of this model, as expressed by the equation:
      specific activity = C(A)e(-alphat) + C(B)e(-betat). The parameters which were
      calculated included the constants C(A), C(B), alpha, and beta; the size of the
      first pool (M(A)); the rate constants for the total rate of removal of
      cholesterol from each pool (k(AA) and k(BB)); and the production rate in pool A
      (PR(A)). In two normal men and five untreated patients the average size of pool A
      was 25g. The effect of cholestyramine was assessed by comparing the results
      obtained without therapy with those obtained during therapy in five subjects
      studied under both conditions. Cholestyramine therapy produced a large increase
      in PR(A) (from 0.98 to 1.98 g/day) and in the rate of removal of cholesterol from
      pool A. Cholestyramine did not significantly alter the size of pool A. It is not
      possible to calculate the size of the total body exchangeable pool of cholesterol
      from the turnover curve of plasma cholesterol. It is also not possible to
      calculate the metabolic turnover rate, i.e., the rate of cholesterol degradation
      and excretion, in the whole body. This parameter can, however, be estimated by
      assuming that cholesterol is removed from the body only by way of the tissue
      pools that comprise pool A. Under these conditions the metabolic turnover rate is
      equal to the production rate in pool A.

PMID- 12066774
TI  - Bile salt malabsorption in regional ileitis, ileal resection and mannitol-induced
      diarrhea.
AB  - Fecal bile salt excretion was studied in healthy volunteers, patients with
      regional ileitis, and patients with ileal resection. 10 muc of carboxyl-(14)C
      cholic acid was given orally. Stools and urine were collected daily for 5-10
      days, the bile salts extracted, and the radioactivity assayed. Urinary excretion
      was negligible. All patients with ileal resection excreted bile salts in the
      feces significantly faster than controls, and five of the six excreted 50% of the
      radioactivity within 24 hr. Their mean intestinal transit time was 5.6 hr
      compared to 26 hr for the controls. Two of the three patients with regional
      ileitis excreted bile salts almost as rapidly as patients with ileal resection.
      Vitamin B(12) absorption was also defective in those patients, but the intestinal
      transit time was not decreased. To study the effect of rapid intestinal transit
      on bile salt excretion, four of the control subjects were given orally 1200 ml of
      10% mannitol for 7 days, and the labeled cholic acid excretion rate was again
      studied. The mean intestinal transit time was markedly shortened, mild
      steatorrhea developed, and the fecal bile salt excretion rate increased slightly.
      It is concluded that ileal resection and ileal disease are major factors and
      rapid intestinal transit is a minor factor in causing excessive fecal bile salt
      loss. The relevance of bile salt wastage to lipid malabsorption is unknown
      because of insufficient information about compensatory jejunal absorption,
      maximum rate of hepatic bile salt synthesis, and the minimum necessary
      intraluminal concentration of conjugated bile salt.

PMID- 12066775
TI  - A pathological inhibitor of fibrin cross-linking.
AB  - Lewis et al. recently reported on a patient who died of hemorrhages attributable
      to an acquired inhibitor of fibrin-stabilizing factor. They indicated that the
      inhibitor was associated with the immune globulins. Using the postmortem serum in
      the isolated fibrin cross-linking system, we have now further localized the site
      of inhibition in the scheme of blood coagulation. The interference occurs at the
      transpeptidation step catalyzed by the thrombin-activated fibrin-stabilizing
      factor. The patient's serum also uniquely delayed the clotting time of Homarus
      plasma, a test for specific inhibitors of transpeptidation. Since the inhibitor
      was effective in two such widely different systems, it probably is not an
      antibody, but falls into the category of cross-linking inhibitors which we have
      previously described (4, 5, 10, 12-17). While the exact nature of the inhibitor
      remains unknown, we raise the question whether some unusual metabolic
      transformation of isonicotinic acid hydrazide (with which the patient was treated
      and which itself we found to be a potent inhibitor fibrin cross-linking), in
      combination with a macromolecule, might not have given rise to an inhibitory
      compound.

PMID- 12066776
TI  - Effects of alpha adrenergic blockade and tissue catecholamine depletion on
      pulmonary vascular response to hypoxia.
AB  - The highly reactive pulmonary vascular bed of the neonatal calf was utilized to
      determine whether the hypoxic pulmonary pressor response is modified by alpha
      adrenergic blockade with phenoxybenzamine (Group A) or by tissue catecholamine
      depletion with reserpine (Group B). In addition, in Group A, the effects of
      hypoxia on the pulmonary circulation were compared and contrasted with those of l
      norepinephrine (alpha-receptor stimulator) and isoproterenol (beta-receptor
      stimulator). In Group A, changes in pulmonary vascular resistance were calculated
      from measurements of appropriate pressures and of pulmonary blood flow
      (electromagnetic flowmeter). The increase in pulmonary vascular resistance
      produced by hypoxia was not diminished by alpha-adrenergic blockade. However,
      blockade abolished the pulmonary vasoconstrictor effect of norepinephrine. During
      hypoxic pulmonary vasoconstriction, the administration of either norepinephrine
      or isoproterenol lowered the pulmonary vascular resistance both before and after
      alpha-blockade. While this may be a true vasodepressor effect of these drugs it
      may also reflect passive changes in the pulmonary vessels secondary to an
      increased pulmonary blood flow.THE PULMONARY VASCULAR RESPONSE TO HYPOXIA IN THE
      RESERPINIZED CALVES (GROUP B) WAS TESTED UNDER THREE CIRCUMSTANCES: (1) in the
      awake animal, (2) in the anesthetized animal prepared in the same way as those in
      Group A, and (3) during constant flow perfusion of the left lower lobe pulmonary
      artery. From these studies it was concluded that tissue catecholamine depletion
      did not diminish the pulmonary vascular response to hypoxia.Thus, neither alpha
      adrenergic blockade nor tissue catecholamine depletion prevents the hypoxic
      pulmonary pressor response. Furthermore, alpha-blockade prevents the pulmonary
      vasoconstrictor response to norepinephrine but not to hypoxia. Therefore it is
      concluded that hypoxic pulmonary vasoconstriction is not mediated through
      adrenergic receptor stimulation or release of endogenous catecholamines.

PMID- 12066777
TI  - Surface tension, metabolic activity, and lipid composition of alveolar cells in
      washings from normal dog lungs and after pulmonary artery ligation. Importance of
      a highly surface-active acellular layer.
AB  - Lung-washings from mammalian species are a rich source of surfactant and of
      cells, predominantly alveolar macrophages, that could be important in the
      metabolism of the surfactant. We obtained washings from normal dogs, and from
      dogs that had had one pulmonary artery (PA) ligated 1 or 2 days earlier.
      Centrifugation of wash (400 x g for 20 min) separated a sediment, made up of
      cells at the bottom and a white layer, largely acellular, from the supernatant.
      The volume of sediment averaged 2.1 +/- 1.4 ml,. 75% of which was white layer.
      The cells resembled the large alveolar (type II) cells found in the lung; however
      they differed by at least one major histochemical reaction. The white layer had
      greater surface activity than the cells or the supernate, and was richest in
      phospholipids and lecithin. The cells lost their surface activity when rinsed and
      resuspended. These observations suggest that surfactant is normally present,
      mainly in an acellular fraction and possibly at the surface of the alveolar
      cells. The alveolar macrophages may either store surfactant, rather than
      synthesize it, or simply acquire a coat of surfactant during sedimentation. After
      PA ligation, the earliest abnormality was a decrease in the white layer; the
      cells were fewer, smaller, and weaker in metabolic activity.

PMID- 12066778
TI  - Glycogen in human peripheral blood leukocytes. II. The macromolecular state of
      leukocyte glycogen.
AB  - Glycogen of normal human blood leukocytes was studied in cell suspensions
      containing chiefly neutrophiles. In electron micrographs of neutrophiles stained
      with lead the glycogen particles appear to be relatively uniform with a diameter
      of 20 mmu. At high magnification the 20 mmu particle appears to be composed of at
      least eight subunits. Leukocyte glycogen released by lysis or homogenization
      sediments as a single peak of high molecular weight material. The great majority
      of the cell glycogen can be accounted for in the large molecular weight material.
      The large molecular weight material is degraded to small fragments by alpha
      amylase and partially degraded by beta-amylase. Purification of cell glycogen by
      alkali extraction and ethanol precipitation produces a relatively uniform
      particle smaller than the original native macromolecule. Native glycogen was
      prepared in pure form by a sucrose density gradient technique and its purity
      demonstrated by its susceptibility to purified alpha-amylase and by analytical
      ultracentrifugation.

PMID- 12066779
TI  - Genetic variants of hemophilia B: detection by means of a specific PTC inhibitor.
AB  - Hemophilia B can be divided into at least two mutant forms different from the
      mild, moderate, and severe categories previously described. In about 90% of
      hemophilia B patients, PTC-inhibitor-neutralizing activity is reduced in
      proportion to PTC clotting activity. In about 10% of the patients, PTC-inhibitor
      neutralizing activity is fully effective, whereas PTC clotting activity is
      reduced. Extensive pedigree studies indicate that the presence or absence of
      inhibitor-neutralizing activity is genetically determined. It is suggested that
      those hemophilia B mutants with decreased inhibitor-neutralizing material produce
      decreased amounts of PTC-protein. It is further suggested that those with normal
      levels of inhibitor-neutralizing material produce normal amounts of PTC-protein,
      which is structurally altered so as to lose procoagulant activity but which
      retains inhibitor-neutralizing activity. The latter group may be analogous to
      CRM(+) mutants described in bacteria and Neurospora.

PMID- 12066780
TI  - Alveolar cells: incorporation of carbohydrate into protein and evidence for
      intracellular protein transport.
AB  - Alveolar cells incubated with radioactive glucosamine, galactose, and mannose
      incorporate radioactivity into protein, that is, into material insoluble in cold
      and hot trichloroacetic acid and not extracted by lipid solvents. This
      incorporation is incompletely inhibited by puromycin hydrochloride. The kinetics
      of the subcellular distribution of radioactivity are consistent with a precursor
      product relationship between microsomal protein and the protein of particles
      sedimenting at 15,000 g. It is thus suggested that alveolar cells incorporate
      these substrates intact into protein at the microsomal level with subsequent
      transfer of this newly formed material to particles sedimenting at 15,000 g.

PMID- 12066781
TI  - Control of myocardial oxygen consumption: relative influence of contractile state
      and tension development.
AB  - Myocardial oxygen consumption was measured in 11 anesthetized, open-chest dogs in
      order to compare in the same heart the relative influence on oxygen usage of
      tension development and the contractile or inotropic state, as reflected in
      V(max.) the maximum velocity of shortening of the unloaded contractile elements.
      The isovolumetrically contracting left ventricle was studied with left
      ventricular volume, heart rate, and systemic perfusion rate controlled. Wall
      tension, contractile element velocity, and V(max) were calculated. Peak developed
      tension was increased at a constant V(max) by increasing ventricular volume, and
      the effect on oxygen consumption was determined. Oxygen utilization was then
      redetermined at an increased V(max) but at a constant peak developed tension by
      infusing norepinephrine (0.76 to 7.6 mug/min) and decreasing ventricular volume
      to match the tension existing before norepinephrine infusion. Oxygen consumption
      consistently increased with increases in both developed tension and V(max) with
      the following multiple regression equation relating these variables: myocardial
      oxygen consumption (mul/beat per 100 g in LV) = K + 0.25 peak developed tension
      (g/cm(2)) + 1.43 V(max) (cm/sec). These data indicate that the oxygen cost of
      augmentation of contractility is substantial, can be independent of any change in
      fiber shortening, and is similar in order of magnitude to the effect of
      alterations in tension development

PMID- 12066782
TI  - Fat-mobilizing action of amphetamine.
AB  - The effects of amphetamine and methamphetamine on plasma free fatty acid (FFA),
      blood glucose, serum total fat, and triglyceride concentrations were investigated
      in 21 subjects; the effect of epinephrine were studied in an identical manner in
      14 subjects. The administration of amphetamine and methamphetamine led to an
      increase in the plasma FFA concentration. No significant changes were found in
      the blood glucose, serum total fat, and triglyceride concentrations. Kinetic
      studies of FFA were also made in some of the subjects receiving amphetamine,
      methamphetamine, and epinephrine. It was shown that amphetamine and
      methamphetamine lead to an augmentation of plasma FFA pool due to a primary
      increase of FFA production rate. Catecholamine depletion, by prolonged parenteral
      adminstration of reserpine, nearly completely abolished the adipokinetic action
      of amphetamine whereas the effect of epinephrine was greatly potentiated. This
      was interpreted as evidence for the dependence of the adipokinetic action of
      amphetamine on endogenous catecholamines. ESTIMATED FROM A DOSE RATIO
      (AMPHETAMINE: epinephrine) of 352:1, the relative adipokinetic potency of
      amphetamine, expressed as peak DeltaFFA rise, +DeltaFFA area, and DeltaFFA
      production rate, respectively, was found to be 55, 84, and 39% in comparison with
      the same effects of epinephrine. The more pronounced changes in +DeltaFFA area
      reflect the longer duration of action of amphetamine viz. epinephrine. This study
      demonstrates that amphetamine is an adipokinetic agent causing an increase in the
      plasma FFA pool of a lesser extent but of longer duration than equipressor doses
      of epinephrine. The mechanism of fat-mobilizing action of amphetamine is indirect
      i.e., dependent on endogenous catecholamine release.

PMID- 12066784
TI  - Absorption of L-methionine from the human small intestine.
AB  - Absorption of L-methionine was measured in all parts of the human small intestine
      using transintestinal intubation and perfusion. In four normal subjects,
      adsorption was higher in the proximal than in the distal intestine. In two
      patients with nontropical sprue in relapse, there was a proximal zone of low
      absorption with higher absorption distally. In all parts of the small intestine,
      absorption showed rate-limiting kinetics as methionine concentration was
      increased. In normal subjects, the proximal K(m) (Michaelis constant) was more
      than 3 times higher than the distal, which suggests a difference in transport
      mechanisms between the two segments.

PMID- 12066783
TI  - Role of anaerobic metabolism in the preservation of functional capacity and
      structure of anoxic myocardium.
AB  - Employing an isolated perfused rat heart preparation, we investigated the
      contribution of anaerobic metabolic energy to the performance, recoverability,
      and ultrastructure of the heart perfused at 32 degrees C in 5% albumin in Krebs
      Ringer Bicarbonate solution. During exposure to anoxia for 30 min, inclusion in
      the perfusate of the anaerobic substrate, glucose, resulted in marked improvement
      in electrical and mechanical performance of the heart and in enhanced recovery
      during the subsequent period of reoxygenation. Lactate production was fivefold
      greater in the glucose-supported anoxic heart than in the anoxic heart without
      glucose. Electron microscope sections of the hearts exposed to anoxia in the
      absence of glucose revealed alterations in mitochondrial morphology and
      dilatation of the longitudinal tubules. These morphologic changes during anoxia
      were averted by inclusion of glucose in the perfusion fluid. The data are
      consistent with the hypothesis that anaerobic energy generation plays a
      significant role in preserving myocardial function and structure and in promoting
      recoverability of the anoxic mammalian heart.

PMID- 12066785
TI  - Outcome of major ABO-incompatible nonmyeloablative hematopoietic stem cell
      transplantation may be influenced by conditioning regimen.

PMID- 12066786
TI  - Effects of adenosine 5'-diphosphate (ADP) receptor blockade on platelet
      aggregation under flow.

PMID- 12066788
TI  - Recurrent involvement of the MLL gene in adult T-lineage acute lymphoblastic
      leukemia.

PMID- 12066787
TI  - Immunocytochemistry reveals RANKL expression of myeloma cells.

PMID- 12066789
TI  - Implication for how the single nucleotide polymorphism (SNP) of Fc receptor, Fc
      gamma RIIIa alters the interaction with anti-CD20 monoclonal antibody.

PMID- 12066790
TI  - Metformin in adolescents with polycystic ovary syndrome: opposed.

PMID- 12066791
TI  - "Whistleblowing as a Whistleblowing as a Failure of Organizational Ethics".

PMID- 12066792
TI  - Optimizing those brain cells.

PMID- 12066793
TI  - Better, faster healing for chronic foot ulcers.

PMID- 12066794
TI  - Mammography: what's a woman to do?

PMID- 12066795
TI  - Reading glasses & beyond: presbyopia prescriptions.

PMID- 12066796
TI  - House calls. What can I do to keep my ankles from swelling?

PMID- 12066797
TI  - House calls. How can I make an appointment with Johns Hopkins physicians,
      including those you mention in the newsletter?

PMID- 12066798
TI  - [Experimental kidney transplantation. 1902].

PMID- 12066799
TI  - Delivery of antibiotics to the eye using a positively charged polysaccharide as
      vehicle.
AB  - The positively charged polysaccharide chitosan is able to increase precorneal
      residence time of ophthalmic formulations containing active compounds when
      compared with simple aqueous solutions. The purpose of the study was to evaluate
      tear concentration of tobramycin and ofloxacin after topical application of
      chitosan-based formulations containing 0.3% wt/vol of antibiotic and to compare
      them with 2 commercial solutions: Tobrex and Floxal, respectively. The influence
      of the molecular weight, deacetylation degree, and concentration of 4 different
      samples of chitosan on pharmacokinetic parameters (area under the curve values
      [AUC(eff)] and time of efficacy [t(eff)]) of tobramycin and ofloxacin in tears
      was investigated over time. It was demonstrated that the 2 chitosan products of
      high molecular weight (1350 and 1930 kd) and low deacetylation degree (50%)
      significantly increased antibiotic availability when compared to the controls,
      with AUC(eff) showing a 2- to 3-fold improvement. The time of efficacy of
      ofloxacin was significantly increased from about 25 minutes to 46 minutes by the
      chitosan of higher Mw (1930 kd) at a concentration of 0.5% wt/vol, whereas a
      similar performance was achieved by a chitosan of low Mw (580 kd) at a
      concentration of 1.5% wt/vol in the case of tobramycin.

PMID- 12066800
TI  - A universal nomenclature for subunits of the RNA polymerase III transcription
      initiation factor TFIIIB.

PMID- 12066801
TI  - Maintaining healthy teeth and gums.

PMID- 12066802
TI  - Sports-related injuries. How to avoid them.

PMID- 12066803
TI  - Health tips. Managing postnasal drip.

PMID- 12066804
TI  - Coronary artery disease may not rule out Viagra use.

PMID- 12066805
TI  - Chelation therapy ineffective as atherosclerosis treatment.

PMID- 12066806
TI  - Smoking cessation. Put your addiction in the ashtray for good.

PMID- 12066807
TI  - Jaw problems. A biting pain.

PMID- 12066808
TI  - Shingles. Seek early treatment.

PMID- 12066809
TI  - Second opinion. My husband recently had bypass surgery following a heart attack.
      Medically, he's the one who needs tending to, but lately I've had episodes of
      shortness of breath and lightheadedness. My husband thinks I'm overly stressed
      and that I'm hyperventilating. Is that possible?

PMID- 12066810
TI  - Second opinion. I recently had a colonoscopy where the doctors found a colon
      polyp that wasn't cancerous and removed it. What can I do to reduce my risk of
      developing more polyps?

PMID- 12066811
TI  - Fluconazole prophylaxis against fungal infection in preterm infants.

PMID- 12066812
TI  - What vitamins should I be taking?

PMID- 12066813
TI  - What vitamins should I be taking?

PMID- 12066814
TI  - Case 26-2001: scleroderma renal crisis and polymyositis.

PMID- 12066815
TI  - Case 26-2001: scleroderma renal crisis and polymyositis.

PMID- 12066816
TI  - Case 26-2001: scleroderma renal crisis and polymyositis.

PMID- 12066817
TI  - Attorney General's intrusion into clinical practice.

PMID- 12066818
TI  - Muscle-powered mechanical blood pumps.

PMID- 12066819
TI  - Human embryos: potential humans?

PMID- 12066820
TI  - Human appropriation of net primary production.

PMID- 12066821
TI  - Fungal diversity and plant roots.

PMID- 12066822
TI  - Effects of simulated microgravity on characteristics of photosynthesis in plant
      seedling.
AB  - OBJECTIVE: To study the effects of simulated microgravity on the characteristics
      of photosynthesis in some plant seedlings. METHOD: Plant samples were treated on
      a 1 pi clinostat rotated at 2 gamma/min for 120 h. Then chlorophyll absorption
      and chlorophyll fast fluorescence induction kinetics were determined. RESULT:
      After treatment on the clinostat: 1) there were some increase in height and
      number of leaves per plant; 2) the strawberry seedlings contained 47.5% less
      chlorophyll and the carnation seedlings contained 4.3% more; 3) there was no
      change in position of the main absorption peaks of chlorophyll in both seedlings
      after the rotation, but their intensity was increased; 4) there were significant
      increase in the parameters of fluorescence induction kinetics in the leaves of
      both seedlings: there was an increase in Fv/Fo, Fv/Fm and T1/2, except CA/Fo; 5)
      there were some differences in excitation energy distribution between the two
      photosystems in the chloroplasts of control and treated samples. CONCLUSION:
      Simulated microgravity does not have a significant effect on normal
      photosynthetic function in chloroplasts, so plant seedlings can grow up normally
      under microgravity.

PMID- 12066823
TI  - [Effects of lower body negative pressure in the first and last week during 21 d
      head-down bed rest on orthostatic tolerance and cardiac function].
AB  - OBJECTIVE: To investigate the changes of orthostatic tolerance and cardiac
      function during 21 d head-down tilt (HDT) bed rest and effect of lower body
      negative pressure (LBNP) in the first and the last weeks in humans. METHOD:
      Twelve healthy male volunteers were exposed to -6 degrees HDT bed rest for 21 d.
      Six subjects received -30 mmHg LBNP sessions for 1 h/d from the 1st to the 7th
      day and from the 15th to the 21st day of the HDT, and the other six who did not
      receive LBNP served as control. Orthostatic tolerance was assessed by means of
      standard tilt test. The cardiac pumping function and cardiac systolic function
      were measured before and during HDT. RESULT: Before HDT, all the subjects in the
      two groups completed the tilt tests. After 10 d and 21 d of HDT, all the subjects
      of the control group and one subject of the LBNP group could not complete the
      tilt test due to presyncopal or syncopal symptoms. The mean time of upright
      standing in the control group (15.0 +/- 3.2 min) was significantly shorter than
      those in the LBNP group (19.7 +/- 0.9 min). The stroke volume and cardiac output
      decreased significantly in the control group on days 3 and 10 of HDT, but
      remained unchanged throughout HDT in the LBNP group. A significant increase in
      preejection period (PEP)/left ventricular ejection time (LVET) was observed on
      days 3 and 14 of HDT in both groups. The PEP/LVET in the LBNP group was
      significantly lower than those in the control group on days 3 of HDT, while LVET
      in LBNP group was significantly higher than those in the control group on days 3,
      7 and 14 of HDT. CONCLUSION: It is suggested that the brief daily LBNP sessions
      in the first and the last weeks were effective in preventing orthostatic
      intolerance and the reduction of cardiac pumping function and cardiac systole
      function induced by 21 d HDT bed rest.

PMID- 12066824
TI  - [Assessment of autonomic nervous function during orthostatic stress in pilots
      with history of syncope].
AB  - OBJECTIVE: To assess the role of autonomic nervous function during orthostatic
      tolerance tests (OTT) in pilots with history of G-induced loss of consciousness
      (G-LOC) or vasovagal syncope (VVS). METHOD: The relation between heart rate
      variability (HRV) and outcome of OTT result were compared among 3 groups of
      cases: 1) 30 patients with history of syncope and positive OTT as patient group
      (PG); 2) 20 cases with history of syncope but negative OTT result as negative
      group (NG); 3) 15 age-, sex-, flight plane model-, flight time-matched healthy
      pilots as healthy control (HC). OTT results and HRV, heart rate (HR), systolic
      blood pressure (SBP) and diastolic blood pressure (DBP) before and after OTT and
      their time and frequency domain were compared and analyzed among the three
      groups. RESULT: HR, SBP, and DBP were not significantly different (P>0.05) among
      the three groups before OTT. But during OTT, HR in PG was higher than those in NG
      and HC (P<0.01), SBP and DBP in PG were lower than those in NG and HC (P<0.01).
      24 h continuous RR interval standard difference (SDNN), HRV triangle index
      (HRVI), and interval average value in PG were significantly lower than those in
      NG and HC; Power spectrum analysis of mean 1 h value for low frequency part (LF)
      and high frequency part (HF) were not significantly different among three groups,
      but LF/HF ratio in PG was higher than that in NG or HC (P<0.05). CONCLUSION: It
      is suggested that G-LOC and VVS may be due to increase in sympathetic tone and
      decrease in parasympathetic tone during orthostatic stimulation, as resulted from
      autonomic nervous dysfunction.

PMID- 12066825
TI  - Accuracy of MMPI-A scales ACK, MAC-R, and PRO in detecting comorbid substance
      abuse among psychiatric inpatients.
AB  - This study investigated the accuracy of various indices involving the MMPI-A
      scales, ACK, MAC-R, and PRO in diagnosing substance abuse in a sample of 79
      psychiatric inpatients. In the full sample, 89.9% of the cases were accurately
      classified by at least one of the three scales. The overall accuracy of
      classification was similar among males, females, Caucasians, and African
      Americans, although there was a tendency for more false positive
      misclassifications among males. Profile code type moderated the accuracy of
      classification with greatest accuracy for code types including Scales 1, 2, 3, 5,
      or 0 and least accuracy for code types including Scales 4, 6, or 9. ACK, MAC-R,
      and PRO were better at screening out cases of substance abuse than in accurately
      identifying those adolescents who were using substances.

PMID- 12066826
TI  - The relationship between the amount of face-to-face contact and partners' reports
      of domestic violence frequency.
AB  - This investigation examines the relationship between partners' amount of face-to
      face contact and partners' frequency of domestic violence. Men entering a
      domestic violence treatment program (N = 134) and their intimate partners were
      asked to complete the Conflict Tactics Scale (CTS) at the beginning of treatment
      and 12 months after treatment completion concerning partner violence during the
      previous year. Partners were also asked to identify days during the year before
      and the year after treatment during which they did not have face-to-face contact.
      Results indicated that at both baseline and 12-month posttreatment follow-up, the
      number of days of face-to-face contact was significantly related to verbal
      aggression and physical violence. However, after controlling for physical
      violence, the relationship between the number of days of face-to-face contact and
      verbal aggression was not significant; the relationship between the number of
      days of face-to-face contact and physical violence remained significant, even
      after controlling for verbal aggression.

PMID- 12066827
TI  - Development of Body Modification and Excessive Exercise Scales for adolescents.
AB  - The present study was designed to develop a Body Modification Scale (BMS) to
      measure body change among adolescents and to modify an Excessive Exercise Scale
      (EES) into a shorter form for adolescents. Two hundred and twenty-one girls and
      192 boys from Grades 7 to 10 completed the BMS and the EES. Factor analysis
      revealed three identical factors for the BMS for girls and boys: weight loss,
      weight gain, and muscle mass. Two identical factors for girls and boys were also
      revealed for the EES. Both factor structures were further validated on a separate
      sample of 286 adolescents (140 girls, 146 boys). The BMS and EES demonstrated
      excellent reliability (alpha > .86) and high test-retest reliability (alpha >
      .82) over 1 month. Good concurrent validity was also found for the weight loss
      factor of the BMS. These findings demonstrate the utility of these two scales for
      use with adolescents.

PMID- 12066828
TI  - Abbreviated form of the Wechsler Memory Scale-III Faces subtest.
AB  - A major criticism of the Wechsler Memory Scale-III Faces subtest is the number of
      items, which can be daunting and time-consuming for an impaired client or boring
      for a normal client. An analysis of several versions, with data from a sample of
      50 clinical referrals, revealed that a 32-item subtest was best overall. Using
      this version, 100% (Faces I) and 94% (Faces II) of the predicted raw scores were
      less than 4 points away from the actual raw scores, whereas 66% (Faces I) and 70%
      (Faces II) were less than 2 points away. Limitations of this procedure are
      discussed.

PMID- 12066829
TI  - Measuring socioeconomic status: reliability and preliminary validity for
      different approaches.
AB  - This study investigated issues related to commonly used socioeconomic status
      (SES) measures in 140 participants from three cities (Atlanta, Boston, and
      Toronto) in two countries (United States and Canada). Measures of SES were two
      from the United States (four-factor Hollingshead scale, Nakao and Treas scale)
      and one from Canada (Blishen, Carroll, and Moore scale). Reliability was examined
      both within (interrater agreement) and across (intermeasure agreement) measures.
      Interrater reliability and classification agreement was high for the total sample
      (ranger = .86 to .91), as were intermeasure correlations and classification
      agreement (range r = .81 to .88). The weakest agreement across measures was found
      when families had one wage earner who was female. Validity data for these SES
      measures with academic and intellectual measures also were obtained. Some support
      for a simplified approach to measuring SES was found. Implications of these
      findings for the use of SES in social and behavioral science research are
      discussed.

PMID- 12066830
TI  - Predicting premature termination from counseling using the Butcher Treatment
      Planning Inventory.
AB  - This investigation examined the extent to which premature termination from
      counseling could be predicted from selected scales on the Butcher Treatment
      Planning Inventory (BTPI). Ninety-five new clients at a university counseling
      center agreed to participate in the study and completed the BTPI as part of the
      intake evaluation. Premature termination occurred when a participant missed a
      scheduled appointment and unilaterally dropped out of counseling. Higher scores
      on Closed-Mindedness, Problems in Relationship Formation, Somatization of
      Conflict, Self-Oriented/Narcissism, Perceived Lack of Environmental Support, and
      the Treatment Difficulty Composite were associated with premature termination.
      The General Pathology Composite, a general index of symptomatic distress, also
      enhanced the prediction of premature termination by suppressing irrelevant
      variance in other BTPI scales. The results provide support for the validity of
      the BTPI in identifying clients at risk for premature termination from
      counseling.

PMID- 12066831
TI  - Effectiveness of Beck Depression Inventory-II subscales in screening for major
      depressive disorders in adolescent psychiatric inpatients.
AB  - The Beck Depression Inventory-II (BDI-II) was administered to 45 male and 55
      female psychiatric inpatients who were 12 to 17 years old, and the Mood Module
      from the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to
      determine whether these patients met criteria for a diagnosis of a DSM-IV major
      depressive disorder (MDD). Binormal receiver-operating-characteristic (ROC)
      analyses found that BDI-II total scores, Cognitive subscale scores, Noncognitive
      subscale scores, and embedded BDI FastScreen for Medical Patients subscale scores
      were comparably effective in differentiating inpatients who were and were not
      diagnosed with a MDD; the areas under the ROC curves were, respectively, .92 (95%
      confidence interval [CI]: .85-.96), .90 (95% CI: .82-.95), .90 (95% CI: .83-.95),
      and .90 (95% CI: .83-.95).

PMID- 12066832
TI  - Factor structure of the Wechsler Adult Intelligence Scale-III in schizophrenia.
AB  - This report examines and compares the factor structure of the new edition of the
      Wechsler Adult Intelligence Scale (WAIS-III) in a sample of chronic schizophrenia
      and schizoaffective disorder outpatients (n = 120) and an age-matched sample of
      individuals drawn from the WAIS-III standardization sample (n = 200). Exploratory
      and confirmatory factor analyses similar to those reported by the developers of
      the scale suggested that a model of WAIS-III performance with correlated factors
      for verbal comprehension, perceptual organization, working memory, and processing
      speed fit the data from the schizophrenia sample as well as it fit the
      nonclinical comparison sample and fit the data from both samples better than
      alternative models.

PMID- 12066833
TI  - The Schedule for Nonadaptive and Adaptive Personality (SNAP): temporal stability
      and predictive validity of the diagnostic scales.
AB  - The authors investigated the test-retest reliability and predictive validity of
      the diagnostic scales from the Schedule for Nonadaptive and Adaptive Personality
      (SNAP). Participants were identified from a sample of 240 undergraduates who
      completed the SNAP and the Social Adjustment Scale (SAS-SR) at Time 1. The
      authors selected 50 people who met criteria for a personality disorder (PD) based
      on the SNAP and 50 who did not qualify for a diagnosis. Eighty-three of these
      people completed the SNAP and the SAS-SR for a second time approximately 9 months
      after initial screening. SNAP PD scales were relatively stable over time. Test
      retest correlation coefficients ranged from .58 to .81. Scores on diagnostic
      scales for paranoid, schizoid, and schizotypal PD were inversely related to self
      reported levels of adjustment for social roles concerned with work as a student,
      leisure activities, and relationships with family. The results provide some
      evidence for the validity of the SNAP

PMID- 12066834
TI  - A quantitative review of the comprehensiveness of the five-factor model in
      relation to popular personality inventories.
AB  - Reports of associations between the five-factor model (FFM) and the scales of
      popular personality inventories have generated controversy regarding the
      comprehensiveness of the FFM. The controversy is fueled by a preoccupation with
      capturing scale variance and differentiating between specific scales, whereas the
      focus should instead be on whether the FFM captures the common variance and the
      dimensions that exist in personality constructs. Analyses of published data
      revealed that the portions of scale variance captured by the FFM (mean = 38%)
      were substantial when evaluated in relation to the portions of common variance
      that exist in most personality inventories (mean = 50%). Furthermore,
      interbattery factor analyses indicated that the factor structures in most
      personality inventories can be closely replicated using data derived solely from
      scale associations with the FFM. Exceptions to this finding occurred for only 2
      of 28 personality inventories. The findings support the comprehensiveness of the
      FFM.

PMID- 12066835
TI  - Paper-and-pencil or online? Evaluating mode effects on measures of emotional
      functioning and attachment.
AB  - The viability of using the World Wide Web to collect data from three widely used
      instruments by clinicians and researchers was investigated. The instruments were
      the Inventory of Parental and Peer Attachment, the Negative Mood Regulation
      Scale, and the Trait Meta-Mood Scale. Data were collected from two comparable
      groups of college students, and differences in response patterns on paper-and
      pencil and World Wide Web versions of the measures, at both the item level and
      scale score level, were documented. Although mode of administration effects were
      statistically significant, the magnitude of the effects was in general very
      small. The basic similarity of the properties of the measures using paper-and
      pencil and online Internet modes of administration suggests the viability of the
      Internet for assessing these and other psychological phenomena.

PMID- 12066836
TI  - Cellular oscillators in animal segmentation.
AB  - Kinetic modeling of developmental dynamics requires detailed knowledge about
      genetic and metabolic networks that underlie developmental processes. However,
      such knowledge is not available for a vast majority of developmental processes.
      Here, we present an coarse-grained, phenomenological model of periodic pattern
      formation in multicellular organisms based on cellular oscillators (CO) that can
      be applied to systems for which little or no molecular data is available. An
      oscillatory process within cells serves as a developmental clock whose period is
      tightly regulated by cell-autonomous and non-autonomous mechanisms. A spatial
      pattern is generated as a result of an initial temporal ordering of the cell
      oscillators freezing into spatial order as the clocks slow down and stop at
      different times or phases in their cycles. When applied to vertebrate
      somitogenesis, the CO model can reproduce the dynamics of periodic gene
      expression patterns observed in the presomitic mesoderm. Different somite lengths
      can be generated by altering the period of the oscillation. There is evidence
      that a CO-type mechanism might also underlie segment formation in certain
      invertebrates, such as annelids and short germ insects. This suggests that the
      dynamical principles of sequential segmentation might be equivalent throughout
      the animal kingdom although most of the genes involved in segment determination
      differ between distant phyla.

PMID- 12066837
TI  - A method for two-dimensional registration and construction of the two-dimensional
      atlas of gene expression patterns in situ.
AB  - We apply the fast redundant dyadic wavelet transform to the spatial registration
      of two-dimensional gene expression patterns of 736 Drosophila melanogaster
      embryos. This method is superior to the Fourier transform or windowed Fourier
      transform because of its ability to reduce noise and is of high resolution. In
      registration of the dataset we use two cost functions based on computing the
      Euclidean or Mahalanobis distance. The algorithm shows a high level of accuracy.
      For early temporal classes the cost function based on Mahalanobis distance gives
      better results. We have reported a method for construction of an integrated
      dataset elsewhere. In this paper the method is extended to the two-dimensional
      case. The procedure for data assembly provides for the preservation of some
      aspects of the nuclear structure of a two-dimensional gene expression pattern. It
      is based on creating an averaged model that reproduces the spatial distribution
      of nuclei over the embryo image. The average concentrations of each protein in
      each averaged nucleus are computed from the series of embryos of the same age.

PMID- 12066838
TI  - In silico determination of potential antisense targets for human beta-globin
      variants.
AB  - The functional characterization of available genomic sequences is the major task
      of the research in the post-genome era. This complex task requires an integrative
      approach of high-throughput systems with in vitro and in vivo models in order to
      have a reliable evaluation of the biological function. The oligonucleotide
      antisense technology is one of the most promising approaches for the
      investigation of gene function; the crucial point of antisense experiments is the
      identification of optimal target sites for hybridisation. In this paper we have
      applied a bioinformatic tool for the recognition of optimal antisense targets. In
      order to evaluate the effect of mutational events on target selection we have
      tested the program on a sample of human beta-hemoglobin variants. The proposed
      algorithm software will be integrated in a web based tool at the site:
      http://www.nettab.org/agewa.

PMID- 12066839
TI  - The GP problem: quantifying gene-to-phenotype relationships.
AB  - In this paper we refer to the gene-to-phenotype modeling challenge as the GP
      problem. Integrating information across levels of organization within a genotype
      environment system is a major challenge in computational biology. However,
      resolving the GP problem is a fundamental requirement if we are to understand and
      predict phenotypes given knowledge of the genome and model dynamic properties of
      biological systems. Organisms are consequences of this integration, and it is a
      major property of biological systems that underlies the responses we observe. We
      discuss the E(NK) model as a framework for investigation of the GP problem and
      the prediction of system properties at different levels of organization. We apply
      this quantitative framework to an investigation of the processes involved in
      genetic improvement of plants for agriculture. In our analysis, N genes determine
      the genetic variation for a set of traits that are responsible for plant
      adaptation to E environment-types within a target population of environments. The
      N genes can interact in epistatic NK gene-networks through the way that they
      influence plant growth and development processes within a dynamic crop growth
      model. We use a sorghum crop growth model, available within the APSIM
      agricultural production systems simulation model, to integrate the gene
      environment interactions that occur during growth and development and to predict
      genotype-to-phenotype relationships for a given E(NK) model. Directional
      selection is then applied to the population of genotypes, based on their
      predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a
      plant-breeding program. The outcomes of the simulated breeding are evaluated
      across cycles of selection in terms of the changes in allele frequencies for the
      N genes and the genotypic and phenotypic values of the populations of genotypes.

PMID- 12066840
TI  - BioDataServer: a SQL-based service for the online integration of life science
      data.
AB  - Regarding molecular biology, we see an exponential growth of data and knowledge.
      Among others, this fact is reflected in more than 300 molecular databases which
      are readily available on the Internet. The usage of these data requires
      integration tools capable of complex information fusion processes. This paper
      will present a novel concept for user specific integration of life science data.
      Our approach is based on a mediator architecture in conjunction with freely
      adjustable data schemes. The implemented prototype is called BioDataServer and
      can be accessed on the Internet: http://integration.genophen.de. To realize a
      comfortable usage of the resulted data sets of the integration process, a SQL
      based query language and a XML data format were developed and implemented.

PMID- 12066841
TI  - High quality visualization of biochemical pathways in BioPath.
AB  - Biochemical reactions form large and complex networks. Comprehensible visual
      representations of these networks help biochemists understand the relationships
      between the chemical components. Typically pathway diagrams are manually produced
      drawings. Because of the steady progress of knowledge and the complex
      relationships in these networks, automatic visualizations are necessary. Bio-Path
      is a system for the exploration and automatic visualization of biochemical
      pathways. It has been developed to obtain an electronic version of the well-known
      Boehringer Biochemical Pathways poster and offers new possibilities to find
      information and to navigate through pathways. BioPath has a specific database
      containing reactions and a hierarchical clustering of reactions and reaction
      networks. One feature is the automatic generation of pathways from the database
      and their high quality visualization. This paper states the requirements for the
      visualization of biochemical pathways, presents a layout algorithm and shows how
      BioPath can be used to explore biochemical reaction networks.

PMID- 12066842
TI  - A database system for the analysis of biochemical pathways.
AB  - To provide support for the analysis of biochemical pathways a database system
      based on a model that represents the characteristics of the domain is needed.
      This domain has proven to be difficult to model by using conventional data
      modelling techniques. We are building an ontology for biochemical pathways, which
      acts as the basis for the generation of a database on the same domain, allowing
      the definition of complex queries and complex data representation. The ontology
      is used as a modelling and analysis tool which allows the expression of complex
      semantics based on a first-order logic representation language. The induction
      capabilities of the system can help the scientist in formulating and testing
      research hypotheses that are difficult to express with the standard relational
      database mechanisms. An ontology representing the shared formalisation of the
      knowledge in a scientific domain can also be used as data integration tool
      clarifying the mapping of concepts to the developers of different databases. In
      this paper we describe the general structure of our system, concentrating on the
      ontology-based database as the key component of the system.

PMID- 12066843
TI  - Operon conservation from the point of view of Escherichia coli, and inference of
      functional interdependence of gene products from genome context.
AB  - We have previously demonstrated that genes within experimentally characterized
      operons of Escherichia coli are conserved together in other genomes more
      frequently than genes at the borders of transcription units. Here we expand the
      analyses and show that, as the phylogenetic distance of the genomes compared
      increases, the genes remaining together must belong to genes associated into
      operons in other prokaryotes regardless of the operon organization of the
      corresponding orthologous gene pair of E. coli. At the same time, we show that
      the observed tendencies of genes within operons to keep very short inter-genic
      distances in E. coli, is the same in any other prokaryote whose genome is
      currently available. We also show the relationship between our analyses of
      conservation and the inference of functional relationships from genomic context.

PMID- 12066844
TI  - GeneNet database: description and modeling of gene networks.
AB  - Almost all cellular processes in an organism are controlled by gene networks.
      Here we report on the analysis of gene networks functioning using two associated
      methods - data accumulation in GeneNet system and generalized chemical kinetic
      method for mathematical simulation of gene network functional dynamics. The
      technology of the usage of these methods is shown on the example of the gene
      network of macrophage activation.

PMID- 12066845
TI  - Intracellular signal transduction in eosinophils and its clinical significance.
AB  - The incidence and prevalence of allergic diseases such as asthma and allergic
      rhinitis have recently been increasing worldwide. Eosinophils are the principal
      effector cells for the pathogenesis of allergic inflammation via the secretion of
      highly cytotoxic granular proteins including eosinophil cationic protein, major
      basic protein and eosinophil protein X. Blood and tissue eosinophilia is a common
      manifestation of late-phase allergic inflammation causing tissue damage. The
      development of eosinophilia correlates with the production of haematopoietic
      cytokines including interleukin (IL)-3. IL-5 and granulocyte macrophage colony
      stimulating factor (GM-CSF), and eosinophil-specific chemoattractant, eotaxin,
      from T-lymphocytes and the epithelium respectively. Elucidation of intracellular
      mechanisms that control the activation, apoptosis and recruitment of eosinophils
      to tissues is therefore fundamental in understanding these disease processes and
      provides targets for novel drug therapy. Over the past decade, there has been
      intensive investigation for the intracellular signal transduction regulating
      various biological functions of eosinophils and their roles in the pathogenesis
      of eosinophil-related diseases. This review will emphasize on the cytokine and
      chemokine-mediated signal transductions including the RAS-RAF-mitogen-activated
      protein kinases (MAPK), Janus kinases (JAK)-signal transducers and activators of
      transcription (STAT), phosphatidylinositol 3-kinase (PI3K) and nuclear factor
      kappa B (NF-kappaB), and various antagonists of receptors and inhibitors of
      intracellular signaling molecules as potential therapeutic agents of allergic
      diseases.

PMID- 12066846
TI  - The effect of nitrostyrene on cell proliferation and macrophage immune responses.
AB  - The use of mood enhancing drugs such as amphetamine and ecstasy are now prevalent
      in society. These compounds are known to produce serious psychological and
      physiological problems in users, which can, in some circumstances result in
      death. While there has been much research into the effects of these drugs on the
      body, little if any research has investigated the effect of the side products and
      synthetic reaction by-products which are a consequence of there illegal
      production. In the study the effects of nitrostyrene, a reaction by-product in
      one of the routes to synthesis of amphetamine sulphate, on cell viability and
      macrophage function was determined. Treatment with nitrostyrene at doses >0.75
      microg/mL had a significant suppressive effect on the proliferation of stomach
      cancer lines. Treatment of macrophages with doses as high as 10 microg/mL did not
      effect cell viability. Nitrostyrene treatment of macrophages, stimulated with IFN
      gamma and LPS, resulted in a dose dependent differential inhibition in IL12, IL6
      and nitrite production, even using doses < 0.5 microg/mL. Thus ranking of the
      three, on the basis of the suppressive effect obtained, is IL12 > nitrite > IL6.
      Thus ingestion of nitrostyrene contaminated ecstasy is likely to have a adverse
      effect on the immune responses of the recreational user.

PMID- 12066847
TI  - Functional dichotomy of a 20-mer and 16-mer peptide derived from Staphylococcus
      aureus protein A: importance of amino acid sequence.
AB  - Protein A (PA) of Staphylococcus aureus possesses a wide variety of biological
      properties such as antitumor, antitoxic, anticarcinogenic, immunomodulatory,
      antifungal and antiparasitic. Since PA is a foreign protein, it is quite logical
      to assume that it may be cleaved into smaller peptide fragments in vivo, which
      may be responsible for the diverse biological activities of whole PA. We have
      shown that two proteolytic peptide fragments (20-mer and 16-mer) of PA mimics IgG
      binding and some of the immunomodulatory properties of PA. In the present study,
      we investigated upon the functional similarity and dissimilarity in these two
      peptides. The 16-mer peptide induces the production of IL6, IL10, TNFalpha and
      IL1alpha but it does not have any effect on secretion of IFNgamma and IL4.
      Whereas 20-mer peptide induces production of TNFalpha, IL1alpha along with
      induction of IFNgamma but it downregulates IL4, IL6 and IL10 production. IFNgamma
      to IL4 ratio clearly indicates that the 20-mer peptide induces Th1 type response,
      whereas 16-mer peptide induces Th0 type response. The 20-mer peptide retains the
      antitumor property of the native protein (PA) in Ehrlich ascitis tumor model,
      whereas 16-mer peptide does retain the same property only in vitro. The 16-mer
      peptide however can activate macrophages to kill Ehrlich ascitis tumor cells in
      vitro more efficiently than that of 20-mer peptide. Thus both the peptides
      although derived from same native protein and has had 13 aminoacid residues in
      common, appears to evoke different reactivites in the immune system. Thus it
      appears that the IgG binding ability which is seen with the native protein A
      molecule and also with both 16-mer and 20-mer peptides do not automatically
      confer upon them the antitumor property, and cytokine producing activities. Thus
      it appears that all different properties associated with Protein A may not be
      necessarily associated with its IgG binding abilities.

PMID- 12066848
TI  - Phosphatidylinositol 3-kinase regulates PMA-induced differentiation and
      superoxide production in HL-60 cells.
AB  - Treatment of the human promyelocytic leukemia cell line HL-60 with phorbol
      myristate acetate (PMA) is associated with induction of monocytic or myelocytic
      differentiation. Since phosphatidylinositol 3-kinase (PI3-kinase) is a critical
      player in cell proliferation, survival, and differentiation, we studied the role
      of PI3-kinase during induction of the differentiated monocytic phenotype and
      superoxide production. In treatment of HL-60 cells with PMA, the PI3-kinase
      inhibitors LY294002 and wortmannin inhibited cell adhesion and spreading and
      phagocytic activity. LY294002 and wortmannin also inhibited the proliferation of
      HL-60 cells. During PMA-induced monocytic differentiation, LY294002 induced
      apoptosis in a dose dependent manner. The phosphorylation of p85alpha derived
      from PMA-stimulated HL-60 cells was shown in the time dependent manner. However,
      p70 S6 kinase inhibitor, rapamycin, did not inhibit PMA-induced monocytic
      differentiation. During PMA-induced monocytic differentiation, LY294002 inhibited
      c-jun protein expression and decrease of c-myc protein level. In contrast,
      LY294002 induced production of superoxide in the HL-60 cells stimulated with
      forskolin. Moreover, staurosporine and H7, PKC inhibitors, enhanced superoxide
      production in dibutyryl cAMP-induced HL-60 cells. These results suggest that PI3
      kinase may regulate PMA-induced differentiation signal and provide a crucial link
      between PKC and cAMP in HL-60 cells.

PMID- 12066849
TI  - Protective effects of Debo on serum-deprived apoptosis of PC12 cells via
      inhibition of H2O2 generation and caspase 3-like protease activity.
AB  - Oxidative stress can be induced neurotoxic insults by increasing intracellular
      H2O2, which has been implicated in various neurodegenerative diseases in aging.
      We investigated the mechanism by which Debo protects PC12 cells from serum
      deprivation-induced apoptosis. PC12 cells underwent apoptotic death in
      association with increase in caspase 3-like activity, DNA fragmentation, H2O2
      production, GSH depletion, and NF-kappaB activation after 24 hr of serum
      withdrawal. Debo protected cells from a serum deprivation-induced cytotoxicity in
      a dose dependent manner. Debo recovered the intracellular GSH level decreased by
      serum deprivation in PC12 cells. Also, Debo inhibited the activation of caspase 3
      like protease of serum-deprived PC12 cells in a dose dependent manner.
      Furthermore, Debo inhibited the transcriptional activation of NF-kappaB by serum
      deprivation. These findings indicate that Debo may protect PC12 cells against
      apoptosis by serum deprivation via generation of intracellular GSH to scavenge
      oxidative radicals including H2O2.

PMID- 12066850
TI  - Suppression of IgE antibody response in mice by a polysaccharide, AZ9, produced
      by Klebsiella oxytoca strain TNM3.
AB  - A soil bacterium, Klebsiella oxytoca TNM3 was found to produce a polysaccharide
      named AZ9 that shows suppressive effects on IgE antibody response in mice. When
      mice were administered with 50 to approximately 100 mg/kg AZ9 subcutaneousely for
      4 consecutive days after immunization with trinitrophenyl (TNP)-keyhole limpet
      hemocyanin, anti-TNP IgE production was significantly suppressed, while the level
      of anti-TNP IgM was affected marginally. In AZ9-administered mice, IL-4 secretion
      from splenic cells was reduced to approximately 30% of the untreated control.
      Thus, AZ9 suppression of IgE production may be due to attenuating effects on the
      Th2-type response. Although oral administration of AZ9 alone had no effects on
      IgE production, ovalbumin (OVA)-induced oral tolerance of anti-TNP IgE response
      to TNP-OVA was markedly augmented when a suboptimal dose of OVA was administered
      orally in combination with AZ9. Collectively, our data suggest that AZ9 has
      beneficial suppressive effects on IgE-dependent allergic responses.

PMID- 12066851
TI  - Enhancement of human T cell response to a peptide epitope of 38 kDa antigen of
      Mycobacterium tuberculosis by liposomes.
AB  - Diagnosis of tuberculosis a problem, specially in the regions harboring an
      abundance of both pathogenic and non-pathogenic mycobacteria. This study was
      undertaken to assess in such a situation the predictive value of proliferative T
      cell response to a peptide epitope ('38G') of the 38 kDa membrane protein of
      Mycobacterium tuberculosis. 3[H]-thymidine incorporation assays were done with
      peripheral blood mononuclear cells of tuberculoid leprosy and pulmonary
      tuberculosis patients. The donors were also classified as PPD responders
      (Stimulation Index, SI> 3) or non-responders (SI < or = 3) on the basis of their
      T cell response to the 'Purified Protein Derivative (PPD)' of M. tuberculosis.
      38G peptide was used in either free or liposome-associated form prepared by the
      technique of 'Dehydration-rehydration Vesicles' (Kirby and Gregoriadis, 1984).
      While free peptide failed to induce a positive response in study subjects, its
      liposomal form was T cell stimulatory and distinguished, to certain extent,
      between PPD responders (corresponding SI > 3 in 54% subjects) and non-responders
      (SI > 3 in 29% subjects). However, it did not differentiate between leprosy and
      tuberculosis. The study supports use of liposomes as adjuvant vehicles for
      antigenic peptides designed to activate human T cells.

PMID- 12066852
TI  - Regulatory effect of cytokine production in asthma patients by SOOJI CHIM (Koryo
      Hand Acupuncture Therapy).
AB  - Acupuncture has become quite familiar to many Koreans not only for pain, but also
      for many other health problems, both in acute and chronic conditions. Actually,
      acupuncture is a therapeutic technique that is part of a larger system of
      traditional oriental medicine. There are several styles of acupuncture. We
      investigated the regulatory effects of cytokine production in peripheral blood of
      asthma patients (AP) by SOOJI CHIM (Koryo Hand Acupuncture Therapy, KHT).
      Clinical signs of asthma disappeared markedly by KHT. The mean interleukin (IL)-2
      and IL-6 plasma levels were lower in the AP group than in the normal group,
      whereas the mean interferon (IFN)-gamma, IL-4, and tumor necrosis factor (TNF)
      alpha levels were higher in the AP group. Plasma IFN-gamma and IL-2 levels
      derived from T helper (Th)1 cells and IL-4 levels derived from Th2 cells were
      elevated in the AP group by KHT. Especially, plasma IL-6 levels derived from Th2
      cells were elevated significantly in the AP group by KHT. Reduced plasma levels
      of TNF-alpha were observed in the AP group by KHT. Plasma IgE levels were also
      measured but there were no significant differences from each other. During the
      KHT, there were no other adverse effects. These results indicate that KHT has a
      good asthma treatment effect, and that its action may be due to the regulation of
      cytokine production.

PMID- 12066853
TI  - Modulation by Acanthospermum australe extracts of the tumor induced hematopoietic
      changes in mice.
AB  - Previous studies on the Ehrlich ascites tumor (EAT) model indicate that tumor
      progression is associated with reduced myelopoiesis and increased extramedullar
      hematopoiesis. In order to investigate the in vivo antitumor activity of
      Acanthospermum australe, its hydroalcoholic extract was partitioned with
      different solvents and the resulting extracts were monitored by their effects on
      bone marrow and spleen hematopoietic progenitor cell proliferation and
      differentiation in EAT-bearing mice. Oral treatment of tumor-bearing mice with 3
      doses of 100, 500 and 1000 mg/kg of the crude hydroalcoholic extract and its
      chloroformic, butanolic and aqueous fractions significantly stimulated
      myelepoiesis and brought extramedullar hematopoiesis back to near control values.
      In normal mice, stimulation of myelopoiesis was only observed with the crude and
      the butanolic extracts. All the extracts at 500 mg/kg significantly increased
      survival of tumor-bearing mice, however a clear survival advantage in the group
      treated with the butanolic extract was observed. These results suggest that A.
      australe may exert effects on myelopoiesis that may be implicated in antitumor
      immune responses.

PMID- 12066854
TI  - Some immunological aspects of patients with rhinitis in Lebanon.
AB  - BACKGROUND: Hitherto immunological determinates in Lebanese patients with
      rhinitis have not been investigated. OBJECTIVE: To identify causative allergens
      in Lebanese patients with allergic rhinitis and determine possible correlation's
      among serum allergen specific antibody, polyclonal IgE, IL-4, IL-5 and peripheral
      eosinophil levels. METHODS: One hundred and thirteen patients with a long lasting
      history of nasal obstruction, rhinorrhea, sneezing and nasal itching were
      investigated. Serum allergen specific antibodies using a panel of 10 potential
      allergens, IL-4 and IL-5 levels were determined by enzyme immunoassays.
      Polyclonal IgE levels were estimated by an immunochromatographic assay and
      eosinophil counts by a Coulter STKS counter. RESULTS: Based on the presence of
      serum allergen-specific IgE antibodies, 74 patients were considered to have an
      allergic etiology. Polyclonal IgE levels were elevated in 41 of the 74 allergic
      rhinitis patients while the other 33 patients had normal serum levels. In the
      remaining 39 specific IgE antibody-negative patients, 32 had normal, and 7 had
      elevated, polyclonal IgE levels. IgE specific antibodies to more than one
      allergen were detected in 59 of 74 patients. The most common causative allergens
      were mite, Dermatophagoides pteronyssinus, Dpt (83.8%) and Dermatophagoides
      farinae, Df (78.4%). Analysis of the data indicated that elevated polyclonal IgE
      levels correlated with the concentration of serum specific IgE antibodies and the
      number of the detected causative allergens per patient. Fifty-nine of 74 allergic
      rhinitis patients had elevated IL-4 levels and 44 had elevated IL-5 levels. The
      number of allergic patients with both elevated IL-4 and IL-5 levels was 24.
      Finally, only 9 allergic rhinitis patients had peripheral eosinophilia.
      CONCLUSION: Mite Dpt and Df were the most common causative agents of allergic
      rhinitis in the Lebanese group studied. A prerequisite for Specific Immunotherapy
      is the identification of the causative allergen. Determinations of polyclonal IgE
      level and peripheral eosinophil count alone, as an aid to diagnosis are
      insufficient and may be misleading. On the other hand, determination of all the
      parameters studied in conjunction appears to be of diagnostic value.

PMID- 12066855
TI  - Inhibition of immediate-type allergic reactions by the aqueous extract of Salvia
      plebeia.
AB  - The effect of aqueous extract of Salvia plebeia R. Brown (Labiatae) (SPAE) on the
      mast cell mediated immediate-type allergic reactions in rats was studied. SPAE
      (0.05 to 1 g/kg) inhibited systemic allergic reaction induced by compound 48/80.
      SPAE (0.001 and 1 g/kg) dose-dependently inhibited passive cutaneous anaphylaxis
      (PCA) when intraperitoneally, intraveneously or orally administered. When SPAE
      was pretreated at the same concentrations with systemic allergic reaction test,
      the plasma histamine levels were reduced in a dose-dependent manner. SPAE (0.001
      to 1 mg/mL) dose-dependently inhibited the histamine release from rat peritoneal
      mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of
      cyclic AMP in RPMC, when SPAE (0.1 and 1 mg/mL) was added, significantly
      increased compared with that of basal cells. Moreover, SPAE (0.01 to 1 mg/mL) had
      a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor
      alpha (TNF-alpha) production. These results indicate that SPAE may possess strong
      antiallergic activity and suggest that differences in bioavailability may cause
      differential activity following different administration routes.

PMID- 12066856
TI  - Latex hypersensitivity: personal data and review of the literature.
AB  - Latex allergy is an increasingly common condition, because use of latex products
      is widespread. The reactions to latex manufactures can be classified as allergic
      and non-allergic, these are the most common. Latex proteins are responsible for
      immediate IgE-mediated hypersensitivity allergic reactions. Symptoms range from
      rhinitis, conjunctivitis and urticaria to anaphylactic shock. Chemical additives
      can cause allergic contact dermatitis. The clinical symptoms of latex allergy
      could arise from direct contact with latex products, but may also result from
      inhalation of airborne allergens. Subpopulations at particular risk include:
      atopics, children with spina bifida or individuals who required frequent surgical
      instrumentations, health care workers, and all persons who have regular contact
      with latex products. Diagnosis of allergy is based initially on history: search
      for specific serum IgE, skin prick test and provocation test may confirm the
      suspicion. The most effective strategy in the treatment of latex allergy is
      avoidance, however this is virtually impossible, given large number of latex
      products we encounter since childhood. In this paper we review the current state
      of knowledge concerning latex allergy, including the clinical spectrum,
      identified allergens, the cross-reactions regarding the latex-fruit syndrome,
      diagnostic procedures and preventive measures. Several personal data increase
      awareness on this issue.

PMID- 12066858
TI  - Effect of holding at room temperature on initial chromatin configuration and in
      vitro maturation rate of equine oocytes.
AB  - The relationship of holding time in media at room temperature (approximately 22
      degrees C) to initial chromatin configuration and rate of in vitro maturation
      (IVM) of equine oocytes was determined. Only oocytes having a complete, compact
      cumulus were used in this study. Oocytes were removed from ovaries 3.5-8 h after
      slaughter and were put into one of four treatment groups: (1) immediate/fix (IF)
      = immediate fixation following removal from the ovary; (2) delay/fix (DF) =
      fixation after oocytes were held 1-4 h in medium at room temperature; (3)
      immediate/mature (IM) = immediate placement into maturation medium at 5% CO2 at
      38.2 degrees C; and (4) delay/mature (DM) = placement into maturation medium at
      5% CO2 at 38.2 degrees C after oocytes were held 1-4 h in medium at room
      temperature. Chromatin configurations in fixed oocytes were classified as
      fluorescent nucleus (FN), condensed chromatin (CC), fibrillar, intermediate, or
      fibrous germinal vesicle (GV). Other classifications were Metaphase I, II, or
      degenerating/abnormal. Oocytes held at room temperature before fixation (DF) had
      a lower proportion of oocytes in the fibrous GV, fibrillar and intermediate
      configurations than did oocytes fixed immediately (IF; 1/54, 2% versus 15/51,
      30%, respectively, P < 0.001). Oocytes held before fixation tended to have a
      higher percentage of both the CC and FN configurations than did oocytes fixed
      immediately (CC: 22/40, 55% versus 11/36, 31%, respectively, P = 0.056; FN:
      17/40, 43% versus 10/36, 28%, respectively, P = 0.066). Holding of oocytes did
      not affect the rate of resumption of meiosis or the rate of degeneration in
      culture; however, of oocytes resuming meiosis, more oocytes in the delayed than
      in the immediate maturation group had reached MII by 24h culture (14/15, 93%
      versus 8/15, 53%, respectively, P = 0.018).

PMID- 12066857
TI  - Comparisons of estradiol, LH and FSH patterns in pregnant and nonpregnant beagle
      bitches.
AB  - To characterize plasma estradiol, LH and FSH patterns of secretion during the
      bitch estrous cycle, blood samples were obtained daily from 15 days before until
      135 days after the LH surge in 10 pregnant and 10 nonpregnant beagle bitches.
      After an initial increase between days 15 and 10 and an expected proestrous peak,
      estradiol concentrations increased again from days 9-12 (corresponding to
      cytological metestrus) from basal values observed around day 9 after the LH
      surge, and remained significantly elevated throughout the luteal phase both in
      pregnant and nonpregnant animals. Concomitantly with the end of the luteal phase,
      plasma concentrations of estradiol returned to basal values in both groups.
      During the mid- to late-luteal phase, mean basal LH secretion was significantly
      elevated throughout in the pregnant relative to the nonpregnant animals. However,
      in nonpregnant animals, pulsatility was increased and peaks of higher amplitude
      were observed. The plasma FSH profiles, determined by a specific homologous RIA,
      differed significantly between pregnant and nonpregnant bitches during the last
      two-thirds of the luteal phase with a mean FSH level more elevated during
      pregnancy. The FSH level then decreased around parturition and low concentrations
      during lactation period were observed. The FSH concentrations remained steady in
      nonpregnant luteal phases from early luteal phase through mid-anestrus. The
      differences in pregnant and nonpregnant LH and FSH concentrations suggest
      pregnancy differences in regulation of the corpus luteum. Finally, the elevated
      estradiol concentrations observed during the luteal phase of both pregnant and
      nonpregnant animals suggest that an ovarian production of estrogens may be
      involved in overall corpus luteum regulation in dogs as in other species.

PMID- 12066859
TI  - Correlation between the age of the conceptus and various ultrasonographic
      measurements during the first 30 days of pregnancy in domestic cats (Felis
      catus).
AB  - We ultrasonographically evaluated the prenatal development in cats, from the
      early phases to Day 30 of pregnancy, subjecting a group of pregnant cats (n = 12)
      to a daily ultrasonographic exam. The ultrasonographic images allowed us to
      measure the minor diameter of the gestational sac and the crown-rump length of
      the embryo/fetus. Ten subjects underwent ovariohysterectomy at specific intervals
      during the pregnancy, with the aim of comparing the ultrasonographic data with
      real data; only two subjects brought their pregnancy to term. The earliest
      ultrasonographic observation of the gestational sac was on Day 10 after mating,
      while the embryo could be measured only beginning with Day 18. This study allowed
      to gather useful new data in order to clinically monitor the normal course of
      pregnancy in cats and to date the gestational age.

PMID- 12066860
TI  - Ultrasonic cervimetry to study the dilatation of the caudal cervix of the cow at
      parturition.
AB  - The objective of this study was to investigate the temporal changes in dilatation
      of the caudal cervix during induced calvings (n = 5). We used ultrasound
      cervimetry, allowing the continuous recording of the distance between a
      transmitting and receiving ultrasound crystal, which were implanted opposite to
      each other on the caudal rim of the cervix. We started recording between 19 and
      21 h after injecting a prostaglandin analogue (PG) on day 272 of gestation. A
      fluid-filled catheter had been introduced transcervically between the fetal
      membranes and the uterine wall for measurements of intra-uterine pressure (IUP).
      While the characteristics of calving varied widely between the five animals, it
      appeared possible to divide the process of dilatation into four phases. During
      the latent phase, which lasted until 25-43 h after PG, no net gain in dilatation
      occurred. We found an acceleration phase (4.3-6.8 h), in which the dilatation
      rate speeds up (0.49-0.84 cm/h) in three of the cows. During the phase of maximum
      slope (lasting 0.5-4.8 h), we measured an even higher rate (1.47-8.48 cm/h),
      decreasing again during the deceleration phase (rate 0.24-2.28 cm/h) in four
      cows. The quality of the IUP measurements precluded us from continuously
      investigating the relationship between cervical dilatation and uterine
      contractions. However, short term simultaneous recordings revealed that the
      cervical opening changed momentarily in the absence of IUP during the latent
      phase, while during the phase of maximum slope, temporary changes of dilatation
      coincided with uterine contractions. We concluded that the method of ultrasound
      cervimetry used in this study provides a valuable way to study the process of
      cervical dilatation in parturient cows in vivo.

PMID- 12066861
TI  - B-mode ultrasonographic examination of the accessory sex glands of boars.
AB  - Thorough examinations of the reproductive system of boars are generally not
      performed on normal boars to be used for breeding; only boars with problems
      undergo a form of a breeding soundness examination. In order for veterinarians to
      identify pathological conditions, the normal architecture of the accessory sex
      glands needs to be described. The purpose of this study was to use B-mode
      ultrasonography to describe the accessory sex glands in the boar and to see if
      transrectal ultrasonography would be a viable option in which to obtain this
      data. Initially, cross-sectional saline bath examinations of accessory sex glands
      were performed on crossbred boar reproductive tracts (n = 4) using B-mode
      ultrasonography equipped with a 5 MHz dual frequency linear array transducer. In
      situ examinations were also performed on terminal line crossbred boars (n = 16)
      ranging in age from 10 to 23 months old using the same ultrasound methodology;
      four boars were under general anesthesia and the remaining 12 were standing in
      crates. Eight boars were abstinent for 2 days and the other eight had ejaculates
      collected 2 h prior to examination. The paired bulbourethral glands are best
      described as a long oval gland with a uniformly echogenic appearance with a large
      anechoic space in the center of the gland extending most of its length. The walls
      of the vesicular glands were found to be thin, with the parenchyma having
      multiple small echolucent areas that appeared to merge and form a central canal.
      The prostate gland was best identified as a pecan-sized gland with a uniform
      echogenic appearance. Visualization of the prostate gland was accomplished with
      more proficiency using the saline bath ultrasonography as compared to in situ
      examinations. All of the accessory sex glands could be examined using both
      methodologies of ultrasonographic examination with a 5 MHz frequency linear array
      transducer. It was determined that each accessory sex gland could be recognized,
      and differences between ejaculated and nonejaculated boars could be identified.
      The results of this study demonstrate that transrectal ultrasonography can be
      used as a diagnostic aid in assessing the accessory sex glands of boars.

PMID- 12066862
TI  - Impact of boar exposure on puberty attainment and breeding outcomes in gilts.
AB  - We examined the most effective method of boar exposure for the attainment of
      puberty in 89 gilts. At 160 days of age, we allocated gilts to daily direct
      contact with a vasectomized boar after movement of pen groups of gilts to a
      detection-mating area (DGB: n = 30); daily direct contact with boars in the gilt
      home pens (DBG: n = 31); or daily fenceline contact between boars and gilts
      housed in individual gilt stalls (FBG: n = 28). DGB gilts were younger (P < or =
      0.05) than FBG gilts at puberty. Direct boar contact reduced the interval from
      initial boar contact to puberty in DGB and DBG gilts, compared to fenceline
      contact in FBG gilts (P < 0.05). There was no difference (P > or = 0.05) between
      treatment for pubertal weight, backfat, lifetime growth rate, or duration of
      first pubertal estrus. Backfat depth and leptin concentration at 160 days of age
      were positively correlated (P < or = 0.05). We detected no relationships between
      leptin or IGF-1 concentration at 160 days of age and the interval from initial
      exposure to a vasectomized boar to puberty (P > 0.05). Based on objective
      criteria, fenceline contact with a boar (BC) during artificial insemination
      improved the quality of artificial insemination compared to no boar contact (NC)
      (P < 0.05).

PMID- 12066864
TI  - Luteal blood flow during the estrous cycle in mares.
AB  - Transrectal color Doppler ultrasound was used for the noninvasive investigation
      of luteal blood flow during the estrous cycle in six mares. Color was displayed
      in Power-Mode, in which the number of color pixels on the ultrasound image is
      related to the number of moving blood cells. Three pictures with a maximum number
      of color pixels of the corpus luteum (CL) during an examination period of about
      20 min were selected and digitized on a laptop equipped with an external frame
      grabber card. The intra-class correlation coefficient for the number of color
      pixels was 0.90. In all estrous cycles similar patterns of changes in (C), in the
      cross-sectional area of sectional planes of the CL (A), and in plasma
      progesterone levels (P) occurred. Variance component estimates for the effect of
      the mare on (C), (A) and (P) were 14, 23 and 4%, for the influence of day of
      estrous cycle they were 41, 5 and 58% and for the effect of estrous cycle they
      were 7, 5 and 5%, respectively. There were high positive correlations between
      cyclic changes in (C) and (P) (r = 0.58; P < 0.0001). The increase in (C) between
      Days 0 and 5 (Day 0: ovulation) remained at high levels until Day 7 and then
      decreased until Day 15. There were relationships between (C) and (A) (r = 0.37; P
      < 0.0001) and between (A) and (P) (r = 0.24; P < 0.05), but correlation
      coefficients were not as high as between (C) and (P). Differences in (C), (A) and
      (P) between estrous cycles within mares and between mares were not related to
      each other (P > 0.05). The results show that transrectal color Doppler sonography
      is a useful, noninvasive method for examining luteal blood flow in mares, and
      that there are cyclic changes and individual differences in the vascularization
      of the CL. The possible influence of luteal perfusion on fertility in mares needs
      to be investigated in further studies.

PMID- 12066863
TI  - Seasonal analysis of semen characteristics, serum testosterone and fecal
      androgens in the ocelot (Leopardus pardalis), margay (L. wiedii) and tigrina (L.
      tigrinus).
AB  - Captive adult male ocelots (Leopardus pardalis, n = 3), margays (L. wiedii, n =
      3) and tigrinas (L. tigrinus, n = 4) in two locations in southern Brazil were
      studied for 14 consecutive months to evaluate the effect of season on testicular
      function. Reproductive evaluations, including testicular measurements,
      electroejaculation and blood collection were conducted monthly. Fecal samples
      were collected weekly for androgen metabolite analysis to assess testicular
      steroidogenic activity. Ocelots had the highest number of motile spermatozoa in
      the ejaculate (114.7+/-15.8 x 10(6); P < 0.05), the highest percentage of
      morphologically normal spermatozoa (82.4+/-1.2%; P < 0.05) and the highest
      concentration of fecal androgens (1.71 vs. 0.14 microg/g; P < 0.05). Margays and
      tigrinas had lower numbers of motile spermatozoa (23.4+/-2.8 x 10(6), 74.2+/-8.9
      x 10(6), respectively), lower percentages of morphologically normal spermatozoa
      (57.4+/-2.8, 59.2+/-3.5%, respectively), and lower fecal androgen concentrations
      (0.15+/-0.01, 0.23+/-0.01 microg/g, respectively). Serum testosterone
      concentrations were similar among the three species. Fecal androgen
      concentrations were not affected by season, with the exception of the ocelot
      where concentrations were higher (P < 0.05) in the summer. Ejaculates were
      collected throughout the year; however, peaks in average sperm production were
      observed during the summer for all species. In summary, this study has identified
      several species differences in male testicular traits among ocelots, margays and
      tigrinas. Results of longitudinal reproductive assessments suggest males of each
      species are capable of breeding throughout the year.

PMID- 12066865
TI  - Transrectal Doppler sonography of uterine blood flow in cows during pregnancy.
AB  - Transrectal Doppler ultrasound was used for the noninvasive investigation of
      uterine blood flow in three cows during pregnancy. The uterine arteries ipsi and
      contralateral to the conceptus were scanned monthly. Blood flow was reflected by
      the following parameters: resistance index (RI), time-averaged maximum velocity
      (TAMV), diameter of the vessel (D) and the volume of blood flow (VOL). RI values
      were negatively correlated to all other blood flow parameters (P < 0.01).
      Positive correlations occurred between TAMV, D and VOL (P < 0.0001). While blood
      flow parameters did not differ between cows (P > 0.05), the month of gestation
      showed a positive effect on RI and negative effects on TAMV, D and VOL (P <
      0.0001). The RI was lower and TAMV, D and VOL higher in the uterine artery
      ipsilateral to the conceptus (P < 0.05). RI values decreased continuously during
      the first 8 months of gestation and remained from then until birth at a
      relatively constant level. While TAMV increased especially in two-thirds of
      pregnancy, a relatively uniform rise of D was noticed. VOL increased
      exponentially with stage of gestation. The results show that transrectal Doppler
      sonography is a suitable, noninvasive method for the examination of uterine blood
      flow during pregnancy in cows. Using this technique it might be possible in the
      future to determine the role of uterine blood flow in cows at the risk of
      abortion.

PMID- 12066866
TI  - Effects of lactation length and an exogenous progesterone and estradiol-17beta
      regimen during embryo attachment on endogenous steroid concentrations and embryo
      survival in sows.
AB  - The hypotheses that short lactation lengths increase embryo mortality by altering
      endogenous post-weaning steroid concentrations, and that an exogenous steroid
      regimen during embryo attachment might increase embryo survival were tested using
      36 s parity sows assigned randomly to a 2 x 2 factorial. Sows were subjected to
      either a short lactation (SL, 13.0 days, n = 25) or a long lactation (LL, 31.5
      days, n = 11), artificially inseminated at first estrus and treated daily with 2
      ml i.m. of either 25 mg progesterone (P4) and 1.25 pg estradiol-17beta (E2)
      (steroid treatment, ST, n = 17) or the vehicle alone (control treatment, CT, n =
      17) on Days 14-20 post-insemination. Blood samples were collected by jugular
      venipuncture from weaning to 24 days post-insemination on alternate days. Sows
      subjected to the SL compared to the LL tended to have a longer weaning-to-estrus
      interval (WEI) (5.3 versus 4.6 days; P < 0. 10), but did not have a significantly
      reduced conception rate (CR) (71 versus 90%; P > 0.10). The SL and LL sows had a
      similar ovulation rate (19.9 versus 21.3 corpora lutea, CL; P > 0.05), but SL
      sows had fewer viable embryos than LL sows (11.5 versus 15.3; P < 0.05) when
      reproductive tracts were recovered 28-32 days post-insemination. In addition,
      even after correction for the difference in number of embryos between groups,
      viable embryos from the SL versus the LL group weighed less (1.63 versus 1.79 g;
      P < 0.05), had a decreased amnion volume (1.02 versus 1.22 ml; P < 0.05) and
      apparently produced less estrogens since estrone sulfate concentration was
      decreased at 24 days post-insemination in SL versus LL sows (4.3 versus 6.3
      ng/ml; P < 0.05). Embryo survival (percentage of CL represented by a viable
      embryo) however, was not different between SL and LL sows (60 versus 74%; P >
      0.05) and no differences in post-weaning P4 or E2 concentrations were apparent.
      Sows that received the ST only tended to have increased P4 concentrations at 16
      days post-insemination compared to CT sows and neither the number of viable
      embryos, nor embryo survival, was increased in ST versus CT sows (14.7 versus
      12.2; P > 0.05 and 66 versus 68%; P > 0.05, respectively). These data suggest
      that short lactations do not increase embryo mortality by inducing aberrant
      endogenous post-weaning P4 or E2 concentrations. It is unclear whether or not
      small, repeated doses of exogenous P4 and E2 during attachment can increase
      embryo survival.

PMID- 12066867
TI  - Pregnancy rates for grade 2 embryos following administration of synthetic GnRH at
      the time of transfer in embryo-recipient cattle.
AB  - To succeed with pregnancy a bovine embryo must overcome the luteolytic mechanism
      and achieve recognition of pregnancy. It is understood that well developed
      embryos are more successful in achieving recognition of pregnancy than poorly
      developed ones. Attempts have been made to assist this recognition of pregnancy
      by utilising a number of hormonal supplements with varying levels of success. A
      study was undertaken to test the hypothesis that supplementation with synthetic
      GnRH at the time of transfer of Grade 2 embryos will enhance pregnancy rates in
      recipients receiving this category of embryo. Pairs of fresh and frozen Grade 2
      embryos (n = 38) from 34 donor animals were allocated to the trial. Thirty eight
      pairs of recipients were used and one of each pair was randomly assigned to
      receive treatment on the day of embryo transfer (Day 7) with 5 ml of gonadorelin,
      containing a synthetic gonadotrophin releasing hormone, 0.1 mg/ml. Pregnancy
      diagnosis was carried out from 42 days post-transfer by either palpation per
      rectum or ultrasound scanning. Treatment, embryo processing, side of transfer,
      parity of recipient, breed of recipient and breed of donor dam showed no
      statistically significant effect on pregnancy rate. The overall pregnancy rate in
      this study was within commercially accepted limits for Grade 2 embryos at 38.2%.
      The pregnancy rates were 34.2 and 42.1% for the GnRH-treated and control groups,
      respectively and were not significantly different at P < 0.05. The failure of
      this treatment to improve pregnancy rates could be due to its effect being
      transitory therefore allowing subsequent pregnancy loss. The timing of the
      treatment post-transfer, treatment dose and potency of the GnRH analogue may also
      play a role in this. Further study is required to determine the hormonal or
      follicular status of prospective candidates for treatment before applying this as
      a whole herd regime.

PMID- 12066868
TI  - Effect of medium milieu on sperm penetration and pronuclear formation of bovine
      oocytes matured in vitro.
AB  - The purpose of the present study was to investigate the optimal concentration of
      osmolarity, calcium and bicarbonate for sperm penetration and formation of
      pronuclei (PN), and to investigate the time required for capacitation,
      penetration across the zona pellucida and formation of PN in bovine cumulus-free
      oocytes matured in vitro. Bovine follicular oocytes collected at slaughter were
      matured and fertilized in vitro. Bovine sperm penetrated the zona pellucida in
      medium containing 240 to 440 mOsm, whereas PN formation was observed in a narrow
      range of osmolarities, from 280 to 360 mOsm. Maximal penetration by spermatozoa
      and PN formation was obtained in the medium with 2.5 mM calcium. High rates of
      spermatozoa penetration were observed in the medium with 37 to 49 mM NaHCO3.
      However, PN were formed regardless of the concentration of NaHCO3. The times
      required for sperm capacitation and penetration through the zona pellucida were
      260 and 50 min, respectively. The first development of PN was recorded at 120 min
      after sperm penetration. Therefore, our study suggests that fertilization ability
      of spermatozoa in vitro appears to be more stable in high concentrations of NaCI.
      Oocytes are more sensitive to osmotic stress than spermatozoa. Calcium is
      required for both sperm penetration and PN formation in cumulus-free oocytes, but
      bicarbonate may be needed mainly for the penetration of spermatozoa.

PMID- 12066869
TI  - Optimization of in vitro bovine embryo production: effect of duration of
      maturation, length of gamete co-incubation, sperm concentration and sire.
AB  - The aim of these experiments was to investigate the effect of duration of IVM,
      duration of gamete co-incubation, and of sperm dose on the development of bovine
      embryos in vitro. In addition, the speed of sperm penetration of six bulls of
      known differing in vivo and in vitro fertility was examined. In Experiment 1,
      following IVM for 16, 20, 24, 28 or 32 h, cumulus oocyte complexes (COCs) were
      inseminated with 1 x 10(6) spermatozoa/ml. After 24 h co-incubation, presumptive
      zygotes were denuded and placed in droplets of synthetic oviduct fluid (SOF). In
      Experiment 2, following IVM and IVF, presumptive zygotes were removed from
      fertilization wells at 1, 5, 10, 15 or 20 h post insemination and placed in
      culture as described above. In Experiment 3, following IVM, COCs were inseminated
      with sperm doses ranging from 0.01 x 10(6) to 1 x 10(6) spermatozoa/ml. Following
      co-incubation for 24 h, presumptive zygotes were placed in culture as described
      above. In Experiment 4, following IVM, oocytes were inseminated with sperm from
      six bulls of known differing field fertility. To assess the rate of sperm
      penetration, oocytes were subsequently fixed every 3 h (up to 18 h) following
      IVF. Based on the results of Experiment 4, in Experiment 5, following IVM for 12,
      18 or 24 h, COCs were inseminated with sperm from two sires with markedly
      different penetration speeds. After 24 h co-incubation, presumptive zygotes were
      denuded and placed in culture. The main findings from this study are that (1) the
      optimal duration of maturation of bovine oocytes in vitro to maximize blastocyst
      yield is 24 h, (2) sperm-oocyte co-incubation for 10 h is sufficient to ensure
      maximal blastocyst yields, (3) sperm concentrations of 0.25 x 10(6) and 0.5 x
      10(6) spermatozoa/ml yielded significantly more blastocysts than any other
      concentration within the range of 0.01 x 10(6) 1 x 10(6) spermatozoa/ml, (4)
      there are marked differences in the kinetics of sperm penetration between sires
      and this may be a useful predictor of field fertility, and (5) the inferior
      development associated with slower penetration rates may in part be overcome by
      carrying out IVF at a time when the actual penetration is most likely to coincide
      with the completion of maturation.

PMID- 12066870
TI  - In vitro fertilizing capacity and chromatin condensation of deep frozen boar
      semen packaged in 0.5 and 5 ml straws.
AB  - The effect of the straw volume employed for semen freezing was studied in 14
      ejaculates from seven boars, by evaluating the viability, IVF capacity and
      chromatin state of spermatozoa. Frozen-thawed semen from 0.5 and 5 ml straws was
      compared to fresh semen. The chromatin condensation degree was determined by flow
      cytometry, using propidium iodide as fluorochrome, and the chromatin stability
      was evaluated by inducing its decondensation with SDS and EDTA. The results
      obtained for IVF, motility and normal apical ridge (NAR) were: 91.64, 78.14 and
      81.47% sperm penetration, 80.78, 68.38 and 70.83% monospermy, 10.86, 9.76 and
      10.64% polyspermy, 87.14, 50.71 and 47.86% motility, 79.14, 56.14 and 53.36% NAR,
      for fresh semen, thawed semen in 0.5 and 5 ml straws, respectively. Frozen-thawed
      spermatozoa showed significantly increased (P < 0.05) chromatin compactness
      compared to fresh spermatozoa (55.42, 48.41 and 47.08 fluorescence units (MIFU),
      for fresh semen, thawed semen in 0.5 and 5 ml straws, respectively). Chromatin
      was significantly more unstable (P < 0.05) in spermatozoa frozen in 0.5 ml straws
      (174.7 MIFU) compared to those frozen in 5 ml straws (155.53 MIFU) or to those in
      fresh semen (149.74 MIFU).

PMID- 12066871
TI  - Uterine and ovarian blood flow during the estrous cycle in mares.
AB  - Uterine and ovarian blood flow was investigated in four mares during two
      consecutive estrous cycles using transrectal color Doppler sonography. The
      uterine and ovarian arteries of both sides were scanned to obtain waves of blood
      flow velocity. The pulsatility index (PI) reflected blood flow. There were
      significant time trends in PI values of all uterine and ovarian blood vessels
      during the estrous cycle (P < 0.05). PI values did not differ between the uterine
      arteries ipsi- and contralateral to the corpus luteum or the ovulatory follicle.
      PI values of the uterine arteries showed a wave shaped profile throughout the
      estrous cycle. The highest PI values occurred on Days 0 and 1 (Day 0 = ovulation)
      and around Day 11, and the lowest PI values were measured around Days 5 and -2 of
      the estrous cycle. During diestrus (Days 0-15) PI values of the ovarian artery
      ipsilateral to the corpus luteum were significantly lower than PI values of the
      contralateral ovarian artery (P < 0.0001). No differences (P > 0.05) in
      resistance to ovarian blood flow occurred between sides during estrus (Days -6 to
      -1). In this cycle stage PI values decreased in both ovarian vessels (P < 0.05).
      During diestrus, high PI values of the ovarian artery ipsilateral to the corpus
      luteum were measured between Days 0 and 2, followed by a decline until Day 6 (P <
      0.05). From this time on, the resistance to blood flow increased continuously
      until Day 15 (P < 0.05). The cyclic blood flow pattern in the contralateral
      ovarian artery was similar to that in the uterine arteries (r = 0.68; P <
      0.0001). No correlations occurred between the diameter of the corpus luteum and
      the PI values of the ipsilateral ovarian artery (P > 0.05) during diestrus.
      During estrus, there was a negative relationship between growth of the diameter
      of the ovulatory follicle and changes in PI values of the dominant ovarian artery
      (r = -0.41; P < 0.05). PI values of the uterine arteries and of the ovarian
      artery ipsilateral to the ovulatory follicle were negatively related to estrogen
      (E) levels in plasma during estrus (uterine arteries: r = -0.21; P < 0.05;
      dominant ovarian artery: r = -0.35; P < 0.05). In diestrus, PI values of the
      dominant ovarian artery were negatively related to plasma progesterone levels (r
      = -0.38; P < 0.0001), but not the PI values of the uterine arteries (P > 0.05).
      The findings of this study show that there are characteristic changes in blood
      supply of the uterus and the ovaries throughout the equine estrous cycle. There
      are negative correlations between resistance to blood flow in the uterine and
      ovarian arteries and the plasma estrogen levels during estrus. In diestrus, there
      is a negative relationship between the resistance to ovarian blood flow and the
      progesterone levels.

PMID- 12066872
TI  - Herding and snaking by the harem stallion in domestic herds.
AB  - Four herds of pony mares, each consisting of a stallion and six mares, were used
      to characterize the nature of herding by the stallion and the factors that
      induced the herding behavior. Herding behaviors were compared among four
      successive treatments (six mares alone, stallion added, two new mares added, and
      entire herd moved to a new pasture). A new treatment was initiated every 7 days
      and behavior was studied for 5 consecutive days (Days 1-5) for each treatment.
      Observations were made every 10 min during a 2-h period for each day. The extent
      of herding was quantitated by the mean distances between mares. The extent of
      snaking (herding with the head and neck extended and ears held back) was scored
      0, 1, 2, or 3 (nil, minimal, intermediate, and maximal, respectively). The mean
      distance among the original mares on Day 1 when the mares were alone was 5.0 mare
      lengths and was reduced (P < 0.05) to 1.9 mare lengths when the stallion was
      added. The mean distance among the original mares of an established stallion/mare
      herd (3.8 mare lengths) was reduced (P < 0.05) on the day the herd was moved to a
      new pasture (1.9 mare lengths), similar to the effect of the introduction of the
      stallion. Scores for the extent of snaking, as well as the extent of herding,
      were highest (P < 0.05) on Day 1 when the stallion was added or the stallion/mare
      herd was moved to a new pasture. The extent of herding and snaking decreased (P <
      0.05) by Day 2 and was seen only occasionally on Days 3-5. The addition of new
      mares to the herd did not induce herding of the original mares. However, the new
      mares maintained mean distances of 8-12 mare lengths from the original mares,
      resulting primarily from chasing by the stallion. By Day 4, the distances between
      the new and original mares were not different (P > 0.05) from the distances among
      the original mares.

PMID- 12066873
TI  - Calculations of oxygen transport by red blood cells and hemoglobin solutions in
      capillaries.
AB  - A theoretical model is developed to investigate the influence of hemoglobin-based
      oxygen carriers (HBOCs) on oxygen transport in capillary-size vessels. A discrete
      cell model is presented with red blood cells (RBCs) represented in their
      realistic parachute shape flowing in a single file through a capillary. The model
      includes the free and Hb-facilitated transport of O2 and Hb-O2 kinetics in the
      RBC and plasma, diffusion of free O2 in the suspending phase, capillary wall,
      interstitium and tissue. A constant tissue consumption rate is specified that
      drives the simultaneous release of O2 from RBC and plasma as the cells traverse
      the capillary. The model mainly focuses on low capillary hematocrits and studies
      the effect of free hemoglobin affinity, cooperativity and concentration. The
      results are expressed in the form of cell and capillary mass transfer
      coefficients, or inverse transport resistances, that relate the spatially
      averaged flux of O2 coming out of the RBC and capillary to a driving force for O2
      diffusion. The results show that HBOCs at a concentration of 7 g/dl reduce the
      intracapillary transport resistance by as much as 60% when capillary hematocrit
      is 0.2. HBOCs with high O2 affinity unload most O2 at the venular end, while
      those with low affinity supply O2 at the arteriolar end. A higher cooperativity
      did not favor O2 delivery due to the large variation in the mass transfer
      coefficient values during O2 unloading. The mass transfer coefficients obtained
      will be used in simulations of O2 transport in complex capillary networks.

PMID- 12066874
TI  - The role of different chemical modifications of superoxide dismutase in
      preventing a prolonged muscular ischemia/ reperfusion injury.
AB  - It is well know that a long period of ischemia followed by reperfusion can create
      an irreversible tissue damage, also due to the excessive generation of oxygen
      derived free radicals. A possibility for avoiding this syndrome is represented by
      the use of free radical scavengers, such as the superoxide dismutase (SOD). The
      current authors compared the results achieved through different modifications of
      this enzyme in an experimental rat hind limb model of ischemia/reperfusion. 60
      rats that had a 4 hour and 30 minute ischemia of the left hind limb were divided
      into four groups of 15 each and treated using a physiological solution (control
      group), native SOD, monomethoxypolyethylene-glycol-SOD (mPEG-SOD) or
      poly(acryloilmorpholine)-SOD (PAcM-SOD). The outcomes obtained in terms of limb
      survival (p < 0.05), as well as histomorphologic studies (p < 0.0005), revealed a
      superior capacity of mPEG-SOD when compared with the other three substances.

PMID- 12066875
TI  - Properties of hydrogel materials used for entrapment of microbial cells in
      production of fermented beverages.
AB  - Approaches using immobilized biological materials are very promising for
      application in different branches of the food industry, especially in the
      production of fermented beverages. Materials tested by our team for the process
      of entrapment belong to the family of charged polysaccharides able to form beaded
      hydrogels by ionotropic gelation (e.g. alginate, pectate, kappa-carrageenan) and
      synthetic polymers (e.g. polyvinyl alcohol) forming bead- and lens-shaped
      hydrogels by thermal sol/gel transition. Concentration of a gel, conditions and
      instrumentation of gelation process, bead and size distribution, porosity,
      diffusion properties, mechanical, storage and operational stability, and many
      other parameters were followed and optimized. Our work has been oriented
      especially to practical applications of immobilized cells. Brewing yeast cells
      were successfully immobilized by entrapment materials and used in a process of
      batch and continual production of beer, including primary and secondary
      fermentation of wort. Other applications include continual production of ethanol
      by fermentation of different saccharide substrates (molasses, glucose syrup,
      wheat hydrolysate), mead and non-alcoholic beverages production.

PMID- 12066876
TI  - Human osteoblast cultures from osteoporotic and healthy bone: biochemical markers
      and cytokine expression in basal conditions and in response to 1,25(OH)2D3.
AB  - The development of methods to culture bone cells has enhanced in vitro studies
      and allowed researchers to investigate bone cell metabolism in healthy tissue and
      in various different bone diseases. Greater knowledge of cultures of pathologic
      bone tissue-derived osteoblasts may be helpful in performing in vitro experiments
      that test biomaterials and therapies to be used in the orthopedic field, since
      this kind of approach better reflects the conditions of clinical relevance to
      many patients. In the present study primary cultures of human osteoblastic cells
      were isolated from donors with osteoporosis (HOB, Human Osteopenic Bone) and
      their respective controls (HNB, Human Normal Bone). They were then characterized
      in baseline conditions and after stimulation with 10(-9) M 1,25(OH2)D3. Specific
      biochemical markers of bone cells and cytokines involved in bone turnover were
      evaluated to assess cell metabolism and any possible differences between
      osteoblasts derived from healthy and osteopenic bone tissue. Under baseline
      conditions, HNB and HOB in vitro cultures showed some differences in
      proliferation (MTT test), PICP, OC and IL-6. The HNB response to 1,25-(OH2)D3
      stimulation differed significantly from that of the HOB cultures but only with
      regard to the MTT test, and ALP and PICP levels; the other selected parameters
      showed a similar behavior for both cultures. The current findings should be taken
      into account when cultures derived from human bone are used for in vitro
      experiments.

PMID- 12066877
TI  - Encapsulation of insulin in chitosan-coated alginate beads: oral therapeutic
      peptide delivery.
AB  - Insulin was encapsulated in calcium alginate beads coated with chitosan. Its
      release from alginate-chitosan and alginate-chitosan-glutaraldehyde beads was
      studied in artificial gastric (pH 1.2) and intestinal (pH 7.5) fluids. By
      comparing the release amounts, the ionic interaction between alginate-chitosan
      matrix with the medium pH's, intestinal fluid was found to be the better. The
      degradation of released insulin was also searched, even after 6 h incubation, the
      beads remained stable and the undegraded insulin seemed to be sufficient for the
      physiological conditions. Consequently, it can be said that the system can be
      offered for oral delivery of the therapeutic peptide drug insulin.

PMID- 12066878
TI  - A spline Laplacian ECG estimator in a realistic geometry volume conductor.
AB  - We have developed a spline-based Laplacian estimator over an arbitrarily shaped
      surface of a volume conductor and tested its applicability to Laplacian
      electrocardiogram (ECG) mapping. In the newly developed algorithm, estimation of
      the parameters associated with the spline Laplacian is formulated by seeking the
      general inverse of a transfer matrix. Only one spline-parameter needs to be
      determined through regularization in order to estimate the realistic geometry
      surface Laplacian from the body surface potentials. It has been demonstrated that
      the rich knowledge on regularization in the inverse problems can be directly
      applied to estimate the spline Laplacian ECG (LECG), such as the discrepancy
      principle. Computer simulations have been conducted to validate the new approach
      in a spherical volume conductor and test the feasibility of mapping cardiac
      electrical sources in a realistic geometry heart-torso model. The present results
      demonstrate that the realistic geometry spline LECG can be estimated conveniently
      from the body surface potentials, is more robust against measurement noise and
      has better performance than the conventional five-point local Laplacian
      estimator.

PMID- 12066879
TI  - Blind deconvolution of ultrasound sequences using nonparametric local polynomial
      estimates of the pulse.
AB  - The problem of reconstructing the reflectivity of a biological tissue is examined
      by means of blind deconvolution of the echo ultrasound signals. It is shown that
      the quality of the reconstruction procedure can be significantly improved when
      initially the ultrasonic pulse is accurately estimated. A new approach to the
      estimation of the ultrasound pulse echo sequences is proposed, using local
      polynomial approximation, which is closely related to the wavelet transform
      theory. This approach can be viewed as a modification of homomorphic
      deconvolution, by using bases different from the Fourier basis of the space of
      square-integrable functions L2. The bases used here are the orthogonal compactly
      supported wavelet bases. It is shown that the locality of the estimate can be
      extremely useful in number of cases of practical interest, resulting in estimates
      with smaller root-mean squared (rms) errors, as compared with estimates employing
      the Fourier basis. This approach is applied to ultrasound signals, for estimation
      of the ultrasound pulse log-spectrum from the log-spectrum of radio-frequency
      (RF) sequences. It is shown, conceptually and experimentally, that the proposed
      approach can provide robust and rapidly computed estimates of the ultrasound
      pulses from the RF-sequences, as obtained in the process of tissue scanning. The
      pulse phase was recovered using the minimum-phase assumption, which was found to
      hold for the transducers in use. The obtained pulse estimates are used for the
      deconvolution of the RF-sequences, which result in stable estimates of the tissue
      reflectivity function, fairly independent of the properties of the imaging
      system. Simulated data, data obtained from several phantoms and from in vitro
      experiments have been processed and the results seem to be quite promising.

PMID- 12066880
TI  - Detection of transient-evoked otoacoustic emissions and the design of time
      windows.
AB  - A new approach to the design of time windows is presented for detection of
      transient-evoked otoacoustic emissions (TEOAE). The windows are designed with
      reference to a minimum mean square error criterion involving the correlation
      properties of the ensemble of responses. Latency information is introduced in the
      detection process by windowing at different scales that result from wavelet
      decomposition. The significance of both subject- and population-specific time
      windows is investigated. The detection performance is evaluated on a health
      screen database consisting of 4989 records. The results show that the present
      approach to windowing yields a significantly better performance in separating
      normal-hearing subjects from hearing-impaired subjects when compared to detection
      based on unwindowed signals. With time windowing, the specificity increased with
      almost 15% at a fixed sensitivity of 90%.

PMID- 12066881
TI  - Deconvolution estimation of nerve conduction velocity distribution.
AB  - A conduction velocity distribution (CVD) estimator that incorporates volume
      conductor modeling of the nerve-evoked response is introduced in this paper. The
      CVD estimates are obtained from two compound nerve action potentials (CNAP)
      recorded at the skin surface. A third channel is introduced in order to assess
      the estimator performance in the experimental case. The relevance of using an
      accurate signal model is shown by comparing the performance of the proposed
      estimator with a previous approach based on a different CNAP model. The
      performance of the proposed estimator is evaluated for simulated and experimental
      data. The study assesses signal-to-noise ratio immunity and sensitivity to errors
      in the model parameters.

PMID- 12066882
TI  - Higher order statistics and neural network for tremor recognition.
AB  - This paper is concerned with the tremor characterization for the purpose of
      recognition. Three different types of tremor are considered in this paper: the
      parkinsonian, essential, and physiological. It has been proven that standard
      second-order statistical description of tremor is not sufficient to distinguish
      between these three types. Higher order polyspectra based on third- and fourth
      order cumulants have been proposed as the additional characterization of the
      tremor time series. The set of 30 quantities based on the polyspectra has been
      proposed and investigated as the features for the recognition of tremor. The
      neural network of the multilayer perceptron structure has been used as a
      classifier. The results of numerical experiments have proven high efficiency of
      the proposed approach. The average error of recognition of three types of tremor
      did not exceed 3%.

PMID- 12066883
TI  - Magnetic resonance electrical impedance tomography (MREIT): simulation study of J
      substitution algorithm.
AB  - We developed a new image reconstruction algorithm for magnetic resonance
      electrical impedance tomography (MREIT). MREIT is a new EIT imaging technique
      integrated into magnetic resonance imaging (MRI) system. Based on the assumption
      that internal current density distribution is obtained using magnetic resonance
      imaging (MRI) technique, the new image reconstruction algorithm called J
      substitution algorithm produces cross-sectional static images of resistivity (or
      conductivity) distributions. Computer simulations show that the spatial
      resolution of resistivity image is comparable to that of MRI. MREIT provides
      accurate high-resolution cross-sectional resistivity images making resistivity
      values of various human tissues available for many biomedical applications.

PMID- 12066885
TI  - An advanced detrending method with application to HRV analysis.
AB  - An advanced, simple to use, detrending method to be used before heart rate
      variability analysis (HRV) is presented. The method is based on smoothness priors
      approach and operates like a time-varying finite-impulse response high-pass
      filter. The effect of the detrending on time- and frequency-domain analysis of
      HRV is studied.

PMID- 12066884
TI  - Detection and measurement of retinal vessels in fundus images using amplitude
      modified second-order Gaussian filter.
AB  - In this paper, the fitness of estimating vessel profiles with Gaussian function
      is evaluated and an amplitude-modified second-order Gaussian filter is proposed
      for the detection and measurement of vessels. Mathematical analysis is given and
      supported by a simulation and experiments to demonstrate that the vessel width
      can be measured in linear relationship with the "spreading factor" of the matched
      filter when the magnitude coefficient of the filter is suitably assigned. The
      absolute value of vessel diameter can be determined simply by using a
      precalibrated line, which is typically required since images are always system
      dependent. The experiment shows that the inclusion of the width measurement in
      the detection process can improve the performance of matched filter and result in
      a significant increase in success rate of detection.

PMID- 12066886
TI  - System design and performance of a unilateral horizontal semicircular canal
      prosthesis.
AB  - We have reported preliminary results regarding a prototype semicircular canal
      prosthesis and concluded that it can provide rotational cues to the nervous
      system. This paper presents the system design of the prosthesis, and also reports
      the prosthesis system performance and effectiveness. The prosthesis delivers
      electrical pulses to the nerve branch innervating the horizontal semicircular
      canal on one side via implanted electrodes. To allow us to encode both directions
      of angular velocity, the baseline stimulation pulse frequency was set at 150 Hz,
      which is somewhat higher than the average firing rate of afferents innervating
      the semicircular canals in normal guinea pigs (approximately 60Hz). A sensor
      measures angular velocity to modulate (increase or decrease) the pulse rate. The
      prosthetic system was provided to a guinea pig whose horizontal canals were
      surgically plugged. The animal responded to the baseline stimulation initially
      and adapted to the baseline stimulation in roughly one day. After this baseline
      adaptation the animal responded to yaw rotation, showing that the function of the
      canals was partially restored. The experiments also show that the nervous system
      adapts to the artificial rotational cue provided via electrical stimulation.

PMID- 12066887
TI  - Intraparenchymal drug delivery via positive-pressure infusion: experimental and
      modeling studies of poroelasticity in brain phantom gels.
AB  - We have used agarose gel to develop a robust model of the intraparenchymal brain
      tissues for the purpose of simulating positive-pressure infusion of therapeutic
      agents directly into the brain. In parallel with that effort, we have synthesized
      a mathematical description of the infusion process on the basis of a poroelastic
      theory for the swelling of the tissues under the influence of the infusate's
      penetration into the interstitial space. Infusion line pressure measurements and
      video microscopy determinations of infusate volume of distribution within the gel
      demonstrate a good match between theory and experiment over a wide range of flow
      rates (0.5-10.0 microliters/min) and have clinical relevance for the convection
      enhanced delivery of drugs into the brain without hindrance by the blood-brain
      barrier. We have put the brain phantom gel and the infusion measurement system
      into routine use in determining performance characteristics of novel types of
      neurosurgical catheters. This approach simplifies the catheter design process and
      helps to avoid some of the costs of in vivo testing. It also will allow
      validation of the elementary aspects of treatment planning systems that predict
      infusion distribution volumes on the basis of theoretical descriptions such as
      those derived from the poroelastic model.

PMID- 12066888
TI  - A phenomenology model of normal sinus rhythm in healthy humans.
AB  - The fractal component in the daytime healthy heartbeat interval data is studied
      from the perspective of cascade in fluid turbulence. Based on the
      electrophysiology of the heart muscle cell, a bounded random cascade model is
      assumed and the scaling property of the model is derived. In application, a
      "cascade decomposition" is proposed to extract the model parameter based on the
      experimental data. Simulation results show that healthy heart rate variability
      (HRV) can be well captured by the multiplicative process and imply the
      significance of sympatho-vagal interaction in the fractal component of long-term
      healthy HRV.

PMID- 12066889
TI  - Growth mechanism of the bacterial flagellar filament.
AB  - The growth of the bacterial flagellar filament occurs at its distal end by self
      assembly of flagellin transported from the cytoplasm through the narrow central
      channel of the flagellum. The cap at the growing end is essential for its growth,
      remaining stably attached while permitting the flagellin insertion. The structure
      of the cap-filament analyzed by electron cryomicroscopy suggested a cap rotation
      mechanism to promote the flagellin self-assembly.

PMID- 12066890
TI  - Structure and role of coupling proteins in conjugal DNA transfer.
AB  - Type IV secretory systems are transmembrane bacterial multiprotein complexes.
      They are pivotal for conjugation, bacterial-induced plant tumour formation, toxin
      secretion and mammalian pathogen intracellular activity. These systems are
      involved in the spread of antibiotic resistance genes among bacteria by enabling
      conjugative DNA transfer. When such translocons transport DNA, they require the
      assistance of multimeric integral inner membrane proteins, the type IV coupling
      proteins. Its structural prototype is plasmid R388 TrwB protein, responsible for
      coupling the relaxosome with the DNA transport apparatus during bacterial
      conjugation. Its monomeric molecular structure is reminiscent of ring helicases
      and AAA ATPases. The quaternary structure is made up by six equivalent protomers
      featuring a flattened sphere resembling F1-ATPase, with a central channel
      traversing the particle, thus connecting cytoplasm and periplasm.

PMID- 12066891
TI  - Molecular biology of cellulose production in bacteria.
AB  - Cellulose biosynthesis has recently been established for a variety of bacteria of
      diverse origin at the phenotypic and genetic levels. Novel regulatory pathways,
      which involve the second messenger bis-(3',5') cyclic diguanylic acid and several
      proteins with the GGDEF domain, participate in the regulation of cellulose
      biosynthesis. The biological significance of cellulose production in
      environmental, commensal and pathogenic bacteria is only punctually resolved.
      This review summarizes current knowledge on cellulose biosynthesis, its
      regulation and biological function.

PMID- 12066893
TI  - The role of integrons in the dissemination of antibiotic resistance among
      clinical isolates of Pseudomonas aeruginosa from an intensive care unit in
      Brazil.
AB  - Eighty-five Pseudomonas aeruginosa isolates resistant to various antibiotics were
      selected from the intensive care unit of a Brazilian hospital and analyzed for
      integron content by PCR. Fifty-four of them had class-1-related integrons, some
      of which were identical. Integron-positive isolates were statistically more
      resistant to aminoglicoside, quinolone and beta-lactam compounds. Ribotyping of
      integron-positive isolates demonstrated the presence of identical integrons among
      genetically unrelated strains in the hospital environment, confirming its role in
      the spread of gene cassettes in bacterial populations of clinical importance.

PMID- 12066892
TI  - Molecular characterization of multiple-drug-resistant Mycobacterium tuberculosis
      isolates from northwestern Russia and analysis of rifampin resistance using
      RNA/RNA mismatch analysis as compared to the line probe assay and sequencing of
      the rpoB gene.
AB  - This investigation evaluated the potential of RNA/RNA mismatch analysis for the
      detection of rifampin resistance among 38 multiple-drug-resistant (MDR) isolates
      of Mycobacterium tuberculosis from northwestern Russia. The results obtained were
      compared with a commercialized line probe assay and rpoB sequencing, and the
      genetic diversity of the isolates was also investigated in parallel using
      spoligotyping and variable number of tandem DNA repeats (VNTR). The mismatch
      analysis revealed 3 distinct RNA cleavage profiles permitting the subdivision of
      the strains into mutation groups 1 to 3, the most common being group 1 (28 of 38
      isolates) that contained a majority of strains with a TCG531>TTG (Ser->Leu)
      mutation, followed by group 2 (6 of 38 isolates) characterized by different
      mutations in the codon CAC526 (His), and group 3 (4 of 38 isolates), all
      characterized by a GAC516(Asp) mutation. Spoligotyping revealed the Beijing type
      to be the most prevalent among mismatch group 1 (24 out of 28 strains),
      suggesting that the most frequent rpoB mutation among the Beijing family in our
      setting was TCG531 >TTG (Ser->Leu). All the Beijing type isolates were also
      characterized by a unique VNTR pattern made up of exact tandem repeats (ETR)-A to
      E of 42435. We conclude that the Beijing genotype constitutes the major family of
      MDR-TB isolates currently circulating in northwestern Russia, and that the in
      house RNA/RNA mismatch analysis may be successfully used for rapid and reliable
      diagnosis of rifampin-resistant tuberculosis in this setting.

PMID- 12066894
TI  - The use of trypsin to solubilize wall proteins from Candida albicans led to the
      identification of chitinase 2 as an enzyme covalently linked to the yeast wall
      structure.
AB  - The use of trypsin to break proteins covalently linked to the yeast walls of
      Candida albicans released approx. 50% of the proteins, but also glucose and N
      acetylglucosamine. Analysis by affinity chromatography indicated that glucose
      and/or N-acetylglucosamine formed part of the same supramolecular complexes with
      mannoproteins. These complexes would represent a new type of cell wall
      structuration in which beta-1,6 glucan and chitin are linked to proteins. An
      internal peptide from a 50-kDa protein released by trypsin was sequenced, showing
      100% identity with chitinase 2 protein and 92% with chitinase 3. The
      electrophoretic mobility of the chitinase 2 protein was changed by treatment with
      EndoH or beta-elimination, indicating that the enzyme was both N- and O
      mannosylated.

PMID- 12066895
TI  - Expression and localization of the Mycobacterium tuberculosis protein tyrosine
      phosphatase PtpA.
AB  - The Mycobacterium tuberculosis open reading frame Rv2234 encodes a low molecular
      weight tyrosine phosphatase named PtpA. Kinetic analyses of PtpA activity reveal
      that it is capable of dephosphorylation of p-nitrophenyl phosphate, as well as a
      variety of phosphotyrosine-containing substrates. In contrast, PtpA showed no
      detectable activity towards substrates containing phosphoserine or -threonine
      residues. Transcriptional analysis reveals that the M. tuberculosis ptpA promoter
      is expressed in the slow-growing Mycobacterium species M. bovis BCG, but not in
      the fast-growing species M. smegmatis. Furthermore, ptpA expression is
      upregulated upon entry of BCG cultures into stationary phase and increases upon
      infection of human monocytes. We also show that, despite the lack of a general
      export pathway signal sequence, the M. tuberculosis PtpA protein can be released
      from both M. tuberculosis and M. smegmatis during growth.

PMID- 12066896
TI  - Construction of new unencapsulated (rough) strains of Streptococcus pneumoniae.
AB  - To construct rough strains of Streptococcus pneumoniae in which the capsule locus
      was completely deleted, a genetic cassette to be used as a donor DNA in
      transformation was developed. The cassette contained an aphIII gene, conferring
      kanamycin resistance, flanked by segments of dexB and aliA. Since, in all strains
      of S. pneumoniae the capsule locus is between dexB and aliA, the DNA segments of
      these two genes allow insertion of a 1354-bp DNA fragment containing aphIII into
      the pneumococcal chromosome, determining the deletion of the whole capsule locus.
      The capsule locus was deleted from the classic type 2 and type 3 Avery's strains,
      from R6 (whose complete genome sequence is released) and Rx1 (the two most
      commonly used transformation recipients), from a type 3 clinical strain and type
      19F clinical isolate G54 (whose draft genome sequence is annotated). The effect
      of capsule removal was tested in 4 isogenic pairs. In unencapsulated strains,
      growth rate increased up to 56% and transformation frequency increased up to 1075
      fold. A correlation was observed between the increase in growth rate and an
      increase in transformation frequency.

PMID- 12066897
TI  - Influence of abiotic factors on the bacteriocinogenic activity of Actinobacillus
      actinomycetemcomitans.
AB  - We evaluated the influence of abiotic factors on antagonistic activity of
      Actinobacillus actinomycetemcomitans strains isolated from periodontal pockets
      and two reference strains (ATCC 29523 and FDC Y4). Antagonistic assays were
      performed by the overlayer method on tryptic soy agar (TSA), brain heart infusion
      agar, thioglycollate agar and brucella agar, added with yeast extract and
      supplemented (S) or not with L-cystine and sodium bicarbonate. Iso-, auto-, and
      heteroantagonism against a wide range of indicator strains were assayed. The
      influence of incubation atmosphere (anaerobic chamber, anaerobic and candle jars)
      and pH (5.0 to 11.0) was also evaluated. Autoantagonism was not observed. TSA-S
      was shown to be the most adequate medium for antagonistic activity expression.
      The widest spectrum of heteroantagonistic activity was also observed on TSA-S.
      The incubation atmosphere affected only the isoantagonistic activity expression.
      Only at pH 8.0 did A. actinomycetemcomitans express bacteriocinogenic activity.
      The lack of standardized methodology to detect antagonistic activity can lead to
      discrepant results and can make data difficult to be compared. This study
      provides information on abiotic factors that influence bacteriocinogenic activity
      expression and suggests adequate culture conditions for testing A.
      actinomycetemcomitans bacteriocin production, contributing to the establishment
      of a reproducible and reliable methodology.

PMID- 12066898
TI  - Anterior paraclinoid aneurysms.
AB  - OBJECT: The characteristics of a previously unclassified paraclinoid aneurysm
      arising from the anterolateral (dorsal) wall of the proximal internal carotid
      artery were retrospectively analyzed in seven patients (five women and two men)
      who were treated surgically for an aneurysm in this unusual location. METHODS:
      One patient presented with subarachnoid hemorrhage (SAH) caused by rupture of
      this aneurysm. The lesions were found incidentally (five cases) or during
      investigation of SAH due to another aneurysm (one case). There was a female
      predominance in this series; all female patients harbored multiple aneurysms. All
      patients underwent surgery. Removal of the anterior clinoid process was necessary
      because the proximal neck of the aneurysm was closely adjacent to the dural ring.
      CONCLUSIONS: This special group of aneurysms is very rare, is located exclusively
      in the intradural space, and carries the risk of SAH. The results of surgical
      treatment for this aneurysm are quite satisfactory.

PMID- 12066899
TI  - Investigations using magnetic resonance imaging: is neurovascular compression
      present in patients with essential hypertension?
AB  - OBJECT: A possible relationship between neurovascular compression of the rostral
      ventrolateral medulla oblongata (RVLM) and essential hypertension is investigated
      using a specifically designed magnetic resonance (MR) imaging method. In
      conjunction with the ninth and 10th cranial nerves, baroreceptor afferents enter
      the RVLM, which represents a crucial relay for regulation of autonomic blood
      pressure. In 1985 Jannetta and coworkers proposed a causal relationship between
      essential hypertension and intraoperatively observed neurovascular compression of
      the left RVLM. METHODS: Currently, MR imaging is the method of choice for the
      assessment of neurovascular relationships at the brainstem. By obtaining axial
      images of a thin-slice turbo inversion-recovery sequence and three-dimensional
      time-of-flight MR angiograms (fast imaging with steady-state precision), the
      authors documented the occurrence of neurovascular contacts with the RVLM at the
      level of the root entry zones (REZs) of the ninth and 10th cranial nerves in 25
      patients with essential hypertension, 30 normotensive volunteers, and 10 patients
      with renal hypertension. Neurovascular contacts with the REZ at the left RVLM
      were found in 32% of patients with essential hypertension, 37% of normotensive
      volunteers, and 20% of patients with renal hypertension. In total, neurovascular
      contacts on either side of the RVLM were documented in 68% of patients with
      essential hypertension, 53% of normotensive volunteers, and 50% of patients with
      renal hypertension. CONCLUSIONS: The results do not support the theory of
      neurovascular compression in cases of essential hypertension. Findings of
      neurovascular contacts on MR images are not indications for decompression
      surgery. For further clarification, however, prospective MR imaging studies
      should be considered in young patients with essential hypertension in whom the
      history of high blood pressure is short.

PMID- 12066900
TI  - Cerebral oxygen and microdialysis monitoring during aneurysm surgery: effects of
      blood pressure, cerebrospinal fluid drainage, and temporary clipping on
      infarction.
AB  - OBJECT: The aim of this study was to investigate potential episodes of cerebral
      ischemia during surgery for large and complicated aneurysms, by examining the
      effects of arterial temporary clipping and the impact of confounding variables
      such as blood pressure and cerebrospinal fluid (CSF) drainage. METHODS: Brain
      tissue PO2, PCO2, and pH, as well as temperature and extracellular glucose,
      lactate, pyruvate, and glutamate were monitored in 46 patients by using
      multiparameter sensors and microdialysis. Baseline data showed that brain tissue
      PO2 decreased significantly, below a mean arterial pressure (MAP) threshold of 70
      mm Hg. Further evidence of its relationship with cerebral perfusion pressure was
      shown by an increase in mean brain tissue PO2 after drainage of CSF from the
      basal cisterns (Wilcoxon test, p < 0.01). Temporary clipping was required in 31
      patients, with a mean total duration of 14 minutes (range 3-52 minutes), causing
      brain tissue PO2 to decrease and brain tissue PCO2 to increase (Wilcoxon test, p
      < 0.01). In patients in whom no subsequent infarction developed in the monitored
      region, brain tissue PO2 fell to 11 mm Hg (95% confidence interval 8-14 mm Hg). A
      brain tissue PO2 level below 8 mm Hg for 30 minutes was associated with
      infarction in any region (p < 0.05 according to the Fisher exact test); other
      parameters were not predictive of infarction. Intermittent occlusions of less
      than 30 minutes in total had little effect on extracellular chemistry. Large
      glutamate increases were only seen in two patients, in both of whom brain tissue
      PO2 during occlusion was continuously lower than 8 mm Hg for longer than 38
      minutes. CONCLUSIONS: The brain tissue PO2 decreases with hypotension, and, when
      it is below 8 mm Hg for longer than 30 minutes during temporary clipping, it is
      associated with increasing extracellular glutamate levels and cerebral
      infarction.

PMID- 12066901
TI  - Temporary ventricular drainage and emergency radiotherapy in the management of
      hydrocephalus associated with germinoma.
AB  - OBJECT: The authors used an alternative strategy to avoid shunt placement for
      hydrocephalus associated with germinoma, and the ensuing complications. METHODS:
      Between 1998 and 2000, five patients presenting with germinomas of the pineal
      area and symptomatic obstructive hydrocephalus were treated with a novel
      strategy. On arrival, they underwent ventriculostomy placement and one of several
      surgical procedures to obtain tissue for diagnosis. Within several days of the
      initial diagnosis, stereotactically guided fractionated radiotherapy was started.
      All patients experienced rapid tumor shrinkage and resolution of hydrocephalus,
      allowing discontinuation of external ventricular drainage without the need for
      permanent shunting of cerebrospinal fluid. To date, follow up reveals 100%
      radiographically and clinically confirmed tumor control. CONCLUSIONS: Prompt
      resolution of hydrocephalus and absence of complications make this a potentially
      valuable therapy for control of germinomas and their symptoms.

PMID- 12066903
TI  - Complications of endoscopic third ventriculostomy.
AB  - OBJECT: The purpose of this prospective investigation was to determine the rate
      of complications associated with endoscopic third ventriculostomy (ETV). METHODS:
      Between March 1993 and October 2001, 193 ETVs were performed in 188 patients at a
      single institution. The age of the patients ranged from 1 month to 85 years (mean
      age 39 years). One procedure had to be abandoned because a severe venous
      hemorrhage blurred the surgeon's view; however, third ventriculostomy was
      successfully accomplished in that patient 14 days later. In addition, there were
      two cases in which significant venous hemorrhages could be controlled
      endoscopically by using irrigation. Postoperative imaging revealed three subdural
      collections, one tiny thalamic contusion, one cortical hemorrhage at the puncture
      site, and one severe subarachnoid hemorrhage (SAH). There were two deaths (1%
      mortality rate) related to the endoscopic procedure; causes of death were one SAH
      from a torn basilar perforating artery and one wound infection leading to
      meningitis and septic multiorgan failure. Three permanent deficits occurred
      (confusion, oculomotor palsy, and diabetes insipidus [1.6% permanent morbidity
      rate]). Transient deficits included four cases of meningitis, three cases of
      cerebrospinal fluid leak, two cases of herniation syndrome, two cases of
      confusion, one case in which there was a decrease of consciousness, two cases of
      oculomotor palsy, and one case in which there was loss of thirst (7.8% transient
      morbidity rate). Misplacement of the fenestration was the main reason for severe
      complications. During the course of the study, the complication rate dropped
      significantly (no incidences of mortality or permanent morbidity occurred during
      the last 100 procedures). CONCLUSIONS: All permanent and fatal complications
      occurred during the authors' very early experience, indicating that a steep
      learning curve was associated with the procedure. Endoscopic third
      ventriculostomy, if performed correctly, is a safe, simple, and effective
      treatment option for various forms of noncommunicating hydrocephalus.

PMID- 12066902
TI  - Biochemical characterization of pediatric brain tumors by using in vivo and ex
      vivo magnetic resonance spectroscopy.
AB  - OBJECT: Magnetic resonance (MR) spectroscopy provides biochemical information
      about tumors. The authors sought to determine the relationship between in vivo
      and ex vivo biochemical characterization of pediatric brain tumors by using MR
      spectroscopy. Their hypothesis was that ex vivo MR spectroscopy provides a link
      between in vivo MR spectroscopy and neuropathological analysis. METHODS: In vivo
      proton MR spectroscopy was performed before surgery in 11 patients with
      neuroepithelial tumors. During resection, a total of 40 tumor biopsy samples were
      obtained from within the volume of interest identified on in vivo MR spectroscopy
      and were frozen immediately in liquid nitrogen. High-Resolution Magic Angle
      Spinning (HRMAS) was used to perform ex vivo MR spectroscopy in these 40 tumor
      biopsy samples. Neuropathological analysis was performed using the same biopsy
      samples, and the tumors were classified as ependymoma, choroid plexus carcinoma,
      pineoblastoma (one each), and pilocytic astrocytoma, medullobastoma, low-grade
      glioma, and glioblastoma multiforme (two each). Ex vivo HRMAS MR spectroscopy
      improved line widths and line shapes in the spectra, compared with in vivo MR
      spectroscopy. Choline (Cho) detected in vivo corresponded to three different
      peaks ex vivo (glycerophosphocholine, phosphocholine [PCho], and Cho). Metabolite
      ratios from in vivo spectra correlated with ratios from ex vivo spectra (Pearson
      correlation coefficient range r = 0.72-0.91; p < or = 0.01). Metabolite ratios
      from ex vivo spectra, such as PCho/ total creatine (tCr) and lipid/tCr,
      correlated with the percentage of cancerous tissue and percentage of tumor
      necrosis, respectively (r = 0.84; p < 0.001). CONCLUSIONS: Agreement between in
      vivo and ex vivo MR spectroscopy indicates that ex vivo HRMAS MR spectroscopy can
      improve resolution of this modality and provide a link between in vivo MR
      spectroscopy and neuropathological analysis.

PMID- 12066904
TI  - High risk of acute deterioration in patients harboring symptomatic colloid cysts
      of the third ventricle.
AB  - OBJECT: Patients harboring colloid cysts of the third ventricle can present with
      acute neurological deterioration, or the first indication of the lesion may
      appear when the patient suddenly dies. The risk of such an occurrence in a
      patient already identified as harboring a colloid cyst is unknown. The goal of
      this study was to estimate the risk of acute deterioration in patients with
      colloid cysts. METHODS: A retrospective study was made of a cohort of patients
      with newly diagnosed colloid cysts who were recruited in The Netherlands between
      January 1, 1993, and December 31, 1997. Seventy-eight patients were identified,
      all of whom displayed symptoms. Twenty-five patients (32%) presented with
      symptoms of acute deterioration; four patients died suddenly and the cysts were
      discovered at autopsy. The overall mortality rate was 12%. Results of a
      multivariate logistic regression analysis demonstrated that no subgroup of
      patients presenting without acute deterioration could be identified on the basis
      of patient age, duration of symptoms, cyst size, or the presence of
      hydrocephalus. The national incidence of colloid cysts in The Netherlands is
      1/10(6) person-years; the prevalence was estimated to be 1800 asymptomatic
      colloid cysts. CONCLUSIONS: Acute deterioration was a frequent presentation among
      a national cohort of Dutch patients harboring symptomatic colloid cysts. The risk
      of acute deterioration in a symptomatic patient with a colloid cyst in The
      Netherlands is estimated to be 34%. The estimated risk for an asymptomatic
      patient with an incidental colloid cyst is significantly lower. These results
      strongly advocate the selection of surgical treatment for patients with
      symptomatic colloid cysts.

PMID- 12066905
TI  - Magnetic resonance neurography studies of the median nerve before and after
      carpal tunnel decompression.
AB  - OBJECT: Recently developed novel MR protocols called MR neurography, which
      feature conspicuity for nerve, have been shown to demonstrate signal change and
      altered median nerve configuration in patients with median nerve compression. The
      postoperative course following median nerve decompression can be problematic,
      with persistent symptoms and abnormal results on electrophysiological studies for
      some months, despite successful surgical decompression. The authors undertook a
      prospective study in patients with carpal tunnel syndrome, correlating the
      clinical, electrophysiological, and MR neurography findings before and 3 months
      after surgery. METHODS: Thirty patients and eight control volunteers were
      recruited to the study. The MR neurography consisted of axial and sagittal images
      (TR = 2000 msec, TE = 60 msec) obtained using a temporomandibular surface coil,
      fat saturation, and flow suppression. Maximum intensity projection images were
      used to follow the median nerve through the carpal tunnel in the sagittal plane.
      Magnetic resonance neurography in patients with carpal tunnel syndrome
      demonstrated proximal swelling (p < 0.001) and high signal change in the nerve,
      together with increased flattening ratios (p < 0.001) and loss of nerve signal in
      the distal carpal tunnel (p < 0.05). Sagittal images were very effective in
      precisely demonstrating the site and severity of nerve compression. After
      surgery, division of the flexor retinaculum could be demonstrated in all cases.
      Changes in nerve configuration, including increased cross-sectional area, and
      reduced flattening ratios (p < 0.001) were seen in all patients. In many cases
      restoration of the T. signal intensity toward that of controls was seen in the
      median nerve in the distal carpal tunnel. Sagittal images were excellent in
      demonstrating expansion of the nerve at the site of surgical decompression.
      CONCLUSIONS: In this study the authors suggest that MR neurography is an
      effective means of both confirming compression of the median nerve and its
      successful surgical decompression in patients with carpal tunnel syndrome. This
      modality may prove useful in the assessment of unconfirmed or complex cases of
      carpal tunnel syndrome both before and after surgery.

PMID- 12066906
TI  - Functional benefits and cost/benefit analysis of continuous intrathecal baclofen
      infusion for the management of severe spasticity.
AB  - OBJECT: Intrathecally delivered baclofen has been used as a treatment for severe
      spasticity since 1984. Despite this, there are uncertainties surrounding the
      benefits of treatment and the costs involved. The authors assessed the evidence
      of benefits and identified costs and the cost/benefit ratio for continuous
      intrathecal baclofen infusion in the treatment of severe spasticity. METHODS: A
      systematic literature review was conducted to estimate the effect of continuous
      intrathecal baclofen infusion on function and quality-of-life (QOL) measures in
      patients with severe spasticity. Outcomes were related to standard QOL scores to
      estimate potential gains in quality-adjusted life years (QALYs). Information on
      the costs of continuous intrathecal baclofen infusion was obtained from hospitals
      in the United Kingdom. This information was combined to estimate the cost/benefit
      ratio for the use of continuous intrathecal baclofen infusion in patients with
      different levels of disability from severe spasticity. Studies indicate that
      bedbound patients are likely to improve their mobility and become able to sit out
      of bed. Patients with severe spasm-related pain are likely to have major
      improvement or complete resolution of this pain. Many other benefits are also
      reported. Such benefits are related to costs per QALY in the range of 6,900
      pounds to 12,800 pounds ($10,550-$19,570 US). CONCLUSIONS: In carefully selected
      patients who have not responded to less invasive treatments, continuous
      intrathecal baclofen infusion is likely to lead to worthwhile functional
      benefits. Continuous intrathecal baclofen infusion has an acceptable cost/benefit
      ratio compared with other interventions that are funded by the health service.

PMID- 12066907
TI  - A metaanalysis comparing the results of pallidotomy performed using
      microelectrode recording or macroelectrode stimulation.
AB  - OBJECT: There is an active debate regarding whether pallidotomy should be
      performed using macroelectrode stimulation or the more sophisticated and
      expensive method of microelectrode recording. No prospective, randomized trial
      results have answered this question, although personnel at many centers claim one
      method is superior. In their metaanalysis the authors reviewed published reports
      of both methods to determine if there is a significant difference in clinical
      outcomes or complication rates associated with these methods. METHODS: A
      metaanalysis was performed with data from reports on the use of unilateral
      pallidotomy in patients with Parkinson disease (PD) that were published between
      1992 and 2000. A Medline search was conducted for the key word "pallidotomy" and
      additional studies were added following a review of the references. Only those
      studies dealing with unilateral procedures performed in patients with PD were
      included. Papers were excluded if they described a cohort smaller than 10
      patients or a follow-up period shorter than 3 months or included cases that
      previously had been reported. The primary end points for outcome were the
      percentages of improvement in dyskinesias and in motor scores determined by the
      Unified PD Rating Scale (UPDRS). Complications were categorized as mortality,
      intracranial hemorrhage, visual deficit, speech deficit, cognitive decline,
      weakness, and other. There were no significant differences between the two
      methods with respect to improvements in dyskinesias (p = 0.66) or UPDRS motor
      scores (p = 0.62). Microelectrode recording was associated with a significantly
      higher (p = 0.012) intracranial hemorrhage rate (1.3 +/- 0.4%), compared with
      macroelectrode stimulation (0.25 +/- 0.2%). CONCLUSIONS: In reports of patients
      with PD who underwent unilateral pallidotomy, operations that included
      microelectrode recording were associated with a small, but significantly higher
      rate of symptomatic intracranial hemorrhage; however, there was no difference in
      postoperative reduction of dyskinesia or bradykinesia compared with operations
      that included macroelectrode stimulation.

PMID- 12066908
TI  - Multichannel auditory brainstem implant: update on performance in 61 patients.
AB  - OBJECT: Neurofibromatosis Type 2 (NF2) has typically resulted in deafness after
      surgical removal of bilateral vestibular schwannomas (VSs). Cochlear implants are
      generally ineffective for this kind of deafness because of the loss of continuity
      in the auditory nerve after tumor removal. The first auditory brainstem implant
      (ABI) in such a patient was performed in 1979 at the House Ear Institute, and
      this individual continues to benefit from electrical stimulation of the cochlear
      nucleus complex. In 1992, an advanced multichannel ABI was developed and a series
      of patients with NF2 received this implant to study the safety and efficacy of
      the device. METHODS: At the time of first- or second-side VS removal, patients
      received an eight-electrode array applied to the surface of the cochlear nucleus
      within the confines of the lateral recess of the fourth ventricle. The device was
      activated approximately 6 weeks after implantation. and patients were tested
      every 3 months for the 1st year after the initial stimulation, and annually
      thereafter. The protocol included a comprehensive battery of psychophysical and
      speech perception tests. CONCLUSIONS: The multichannel ABI proved to be effective
      and safe in providing useful auditory sensations in most patients with NF2. The
      ABI improved patients' ability to communicate compared with the lipreading-only
      condition, it allowed the detection and recognition of many environmental sounds,
      and in some cases it provided significant ability to understand speech by using
      just the sound from the ABI (with no lipreading cues). Its performance in most
      patients has continued to improve for up to 8 years after implantation.

PMID- 12066909
TI  - Role of a synthetic pyrimidine compound, MS-818, in reduction of infarct size and
      amelioration of sensorimotor dysfunction following permanent focal cerebral
      ischemia in rats.
AB  - OBJECT: A synthetic heterocyclic pyrimidine compound, MS-818 (2-piperadino-6
      methyl-5-oxo-5,6-dihydro-(7H) pyrrolo-[3,4-d] pyrimidine maleate) is reported to
      have a variety of biological activities including neurite outgrowth, astrocyte
      differentiation, suppression of neuronal apoptosis, regeneration of injured
      peripheral nerves, fracture repairs, angiogenesis, and superovulation. To be able
      to explicate the neurotrophic effects of MS-818, the authors evaluated its effect
      on the reduction of infarct volume and amelioration of sensorimotor dysfunction
      in a rat model of focal ischemia. METHODS: Forty male Sprague-Dawley rats were
      subjected to right middle cerebral artery occlusion and assigned to one of four
      treatment groups (10 animals in each group). The MS-818 (1, 5, or 10 mg/kg) or
      phosphate-buffered saline (control group) was administered intraperitoneally at
      onset of ischemia and again 24 hours later. The rats were killed 48 hours after
      they underwent surgery to induce stroke, and infarct volume was determined using
      an image-analysis computer software program following staining with 2,3,5
      triphenyltetrazolium chloride. Postischemic neurological deficit and body weight
      were also assessed. CONCLUSIONS: Significant reductions in infarct volume (total
      and cortical infarction) were found in all the MS-818-treated groups compared
      with the control group. Furthermore, MS-818 induced significant amelioration of
      sensorimotor dysfunction, as indicated by the results of forelimb and hindlimb
      placing tests. The present findings suggest that MS-818, which has a much smaller
      molecular weight than neurotrophic peptides. represents a new approach to the
      treatment of focal cerebral ischemia.

PMID- 12066910
TI  - Stilbazulenyl nitrone, a novel azulenyl nitrone antioxidant: improved
      neurological deficit and reduced contusion size after traumatic brain injury in
      rats.
AB  - OBJECT: Stilbazulenyl nitrone (STAZN) is a second-generation azulenyl nitrone
      that has markedly enhanced antioxidant properties compared with those of
      conventional alpha-phenyl nitrones. In this study, the authors assessed the
      potential efficacy of STAZN in a rodent model of fluid-percussion brain injury,
      which results in a consistent cortical contusion. METHODS: After anesthesia had
      been induced in normothermic Sprague-Dawley rats (brain temperature 36-36.5
      degrees C) by halothane-nitrous oxide, the animals were subjected to a right
      parietooccipital parasagittal fluid-percussion injury (1.5-2 atm). The agent
      (STAZN, 30 mg/kg: eight animals) or vehicle (dimethyl sulfoxide; eight animals)
      was administered intraperitoneally at 5 minutes and 4 hours after trauma. The
      neurological status of each rat was evaluated on Days 1, 2, and 7 postinjury
      (normal score 0, maximum injury 12). Seven days after trauma, the rat brains were
      perfusion fixed, coronal sections at various levels were digitized, and areas of
      contusion were measured. Treatment with STAZN significantly improved neurological
      scores on Days 2 and 7 postinjury compared with vehicle-treated rats.
      Administration of STAZN also significantly reduced the total contusion area by
      63% (1.8 +/- 0.5 mm2 in STAZN-treated animals compared with 4.8 +/- 2.1 mm2 in
      vehicle-treated animals; p = 0.04) and the deep cortical contusion area by 60%
      (1.2 +/- 0.2 mm2 in STAZN-treated animals compared with 2.9 +/- 1.2 mm2 in
      vehicle-treated animals; p = 0.03). By contrast, hippocampal cell loss in the CA3
      sector was unaffected by STAZN treatment. CONCLUSIONS: Therapy with STAZN, a
      novel potent antioxidant, administered following traumatic brain injury, markedly
      improves neurological and histological outcomes. Azulenyl nitrones appear to
      represent a promising class of neuroprotective agents for combating this
      devastating condition.

PMID- 12066911
TI  - Correlation between changes in apparent diffusion coefficient and induction of
      heat shock protein, cell-specific injury marker expression, and protein synthesis
      reduction on diffusion-weighted magnetic resonance images after temporary focal
      cerebral ischemia in rats.
AB  - OBJECT: The authors investigated the relationship between the time course of
      apparent diffusion coefficient (ADC) changes and stress protein induction,
      ischemic neuroglial damage, and cerebral protein synthesis (CPS) after temporary
      focal cerebral ischemia in rats. METHODS: In Group I, ADC changes were measured
      on magnetic resonance (MR) images obtained during the second half of a 1-hour
      middle cerebral artery (MCA) occlusion, during a 1-hour reperfusion, and after 23
      hours of reperfusion in rats. Immunohistochemical studies for heat shock protein
      (hsp) 70, glial fibrillary acidic protein (GFAP), and neuronal nuclear (NeuN)
      protein were performed. In Group II, CPS was assessed using autoradiographic
      studies obtained after occlusion. At 36 minutes of occlusion, MR imaging
      demonstrated significantly less ADC reduction in the frontoparietal cortex (82 +/
      9% of the contralateral hemisphere) than in the striatum (64 +/- 11%; p < 0.05).
      After 1 hour of reperfusion, the lesion resolved and the difference between
      cortex and striatum was no longer evident. After 23 hours of reperfusion, the ADC
      lesion recurred in striatum (76 +/- 12%) compared with frontoparietal cortex (100
      +/- 11%; p < 0.05). Immunohistochemical studies showed hsp 70 expression and an
      increased GFAP reactivity localized in the frontoparietal cortex of the ischemic
      hemisphere, along with a significant drop in striatal NeuN immunoreactivity. A
      trend toward greater reduction in striatal CPS (53 +/- 15%) than in
      frontoparietal cortex CPS (78 +/- 23%) was also observed. CONCLUSIONS: Sequential
      ADC maps correlate with the expression of neuroglial stress and injury markers
      after temporary focal ischemia in rats, distinguishing the striatum (infarct
      core) from the cortex (ischemic penumbra). A greater reduction in striatal CPS
      further supports the conclusion that the striatum is more susceptible to
      temporary MCA occlusion than the cortex.

PMID- 12066912
TI  - Heme oxygenase-1 gene therapy for prevention of vasospasm in rats.
AB  - OBJECT: Hemoglobin causes contraction of cerebral arteries and is also believed
      to cause vasospasm after subarachnoid hemorrhage (SAH). The goal in this study
      was to determine if overexpression of heme oxygenase-1 (HO-1), the principal
      enzyme involved in the metabolism of hemoglobin, would reduce contractions of
      cerebral arteries brought on by hemoglobin and decrease vasospasm after
      experimental SAH. METHODS: Injection of adenovirus expressing HO-1 (Ad5HO-1) into
      the cisterna magna of rats produced a significant increase in expression of HO-1
      messenger RNA, and protein and HO-1 activity in the basilar artery ([BA]; p <
      0.05 for each measure compared with vehicle and/or control virus, according to
      analysis of variance or unpaired t-test). Injection of adenovirus expressing beta
      galactosidase (Ad-betaGal) produced only mild, statistically nonsignificant
      increases. The HO-I immunoreactivity was localized to the BA adventitia after
      injection of Ad5HO-1 or Ad-betaGal. Injection of Ad5HO-1 and Ad-betaGal increased
      the baseline diameter of the BA (measured directly via a transclival window) and
      brainstem cerebral blood flow (CBF), measured by laser Doppler flowmetry,
      compared with vehicle. Contraction of the BA after addition of hemoglobin was
      significantly inhibited, reduction in brainstem CBF was significantly prevented,
      and carboxyhemoglobin concentration was significantly increased in rats injected
      with Ad5HO-1 compared with Ad-betaGal and vehicle. Vasospasm was significantly
      ameliorated in rats in which Ad5HO-1 was injected into the cisterna magna at the
      time of SAH in a double-hemorrhage model. CONCLUSIONS: These results show that
      overexpression of HO-1 inhibits arterial contractions induced by hemoglobin and
      can reduce vasospasm after experimental SAH.

PMID- 12066913
TI  - The tentorial notch: anatomical variation, morphometric analysis, and
      classification in 100 human autopsy cases.
AB  - OBJECT: Variations in the structure of the tentorial notch may influence the
      degree of brainstem distortion in transtentorial herniation, concussion, and
      acceleration-deceleration injuries. The authors examined the anatomical
      relationships of the mesencephalon, cerebellum, and oculomotor nerves to the
      dimensions of the tentorial aperture. On the basis of numerical data collected
      from this study, the authors have developed the first classification system of
      the tentorial notch and present new neuroanatomical observations pertaining to
      the subarachnoid third cranial nerve and the brainstem. METHODS: The
      mesencephalon was sectioned at the level of the tentorial edge in 100 human
      autopsy cases (specimens from 23 female and 77 male cadavers with a mean age at
      time of death of 42.5 years [range 18-80 years]). The following measurements were
      determined: 1) anterior notch width, the width of the tentorial notch in the
      axial plane through the posterior aspect of the dorsum sellae; 2) maximum notch
      width (MNW), the maximum width of the notch in the axial plane; 3) notch length
      (NL), the length of the tentorial notch from the superoposterior edge of the
      dorsum sellae to the apex of the notch; 4) posterior tentorial length, the
      shortest distance between the apex of the notch and the most anterior part of the
      confluence of the sinuses; 5) interpedunculoclival (IC) distance, the distance
      from the interpeduncular fossa to the superoposterior edge of the dorsum sellae;
      6) apicotectal (AT) distance, the distance from the tectum in the median plane to
      a perpendicular line dropped from the apex of the tentorial notch to the
      cerebellum; 7) cisternal third nerve distance, the distance covered by the
      cisternal portion of the third cranial nerve; and 8) inter-third nerve angle, the
      angle between the two third cranial nerves. The quartile distribution technique
      was applied to all measurements. Mean values are presented as the means +/-
      standard deviations. Quartile groups defined by NL (mean 57.7 +/- 5.6 mm) were
      labeled long, short, and midrange, and those defined by MNW (mean 29.6 +/- 3 mm)
      were labeled wide, narrow, and midrange. Combining these groups into a matrix
      formation resulted in the classification of the tentorial notch into the
      following eight types: 1) narrow (15% of specimens); 2) wide (12% of specimens);
      3) short (8% of specimens); 4) long (15% of specimens); 5) typical (24% of
      specimens); 6) large (9% of specimens); 7) small (10% of specimens); and 8) mixed
      (7% of specimens). The IC distance (mean 20.4 +/- 3.2 mm) was used to
      characterize brainstem position as prefixed (28% of specimens), postfixed (36% of
      specimens), or midposition (36% of specimens). The IC distance was correlated
      with the left and right cisternal third nerve distances (means 26.7 +/- 2.9 mm
      and 26.1 +/- 3.2 mm, respectively) and the inter-third nerve angle (mean 57.3 +/-
      7.3 degrees). The exposed cerebellar parenchyma within the notch, the
      relationship between the brainstem and tentorial edge, and the brainstem position
      varied considerably among individuals. The cisternal third nerve distance, its
      trajectory, and its anatomical relation to the skull base also varied widely. Two
      anatomically distinct segments of the subarachnoid third cranial nerves were
      characterized with respect to the skull base as suspended and supported segments.
      CONCLUSIONS: The authors present a new classification system for the tentorial
      aperture to help explain variations in herniation syndromes in patients with
      otherwise similar intracranial pathological conditions, and responses to
      concussive and acceleration-deceleration injuries. The authors present
      observations not previously described regarding the position of the brainstem
      within the tentorial aperture and the cisternal portion of the third cranial
      nerves. A significant statistical correlation was discovered among specific
      morphometric parameters of the tentorial notch, brainstem, and oculomotor nerves.
      These findings may have neurosurgical implications in clinical situations that
      cause brainstem distortion. Additionally, this analysis provides baseline data
      for interpreting magnetic resonance and computerized tomography images of the
      tentorial notch and its regional anatomy.

PMID- 12066914
TI  - Detailed anatomy of the intracranial segment of the hypoglossal nerve:
      neurovascular relationships and landmarks on magnetic resonance imaging
      sequences.
AB  - OBJECT: The thin hypoglossal nerve can be very difficult to distinguish on
      magnetic resonance (MR) images. The authors used a combination of sequences to
      increase the reliability of MR imaging in its demonstration of the 12th cranial
      nerve as well as to assess the course of the nerve, display its relationships to
      adjacent vessels, and provide landmarks for evaluating the nerve in daily
      practice. METHODS: The study group consisted of 34 volunteers (68 nerves) in whom
      a three-dimensional (3D) Fourier-transformation constructive interference in
      steady-state (CISS) sequence and a 3D T1-weighted contrast-enhanced magnetization
      prepared rapid-acquisition gradient-echo (MPRAGE) sequence were applied. Two
      trained neuroradiologists collaboratively identified the hypoglossal trigone,
      preolivary sulcus, 12th cranial nerve, posterior inferior cerebellar artery,
      vertebral artery, 12th nerve root sleeve, and the hypoglossal canal on each side.
      The 3D CISS sequence successfully demonstrated the hypoglossal trigone (100% of
      images), 12th nerve root bundles (100% of images), and 12th nerve sleeves (88.2%
      of images). The canalicular segment was exhibited with the aid of plain 3D CISS
      sequences in 74% of images and by using contrast-enhanced 3D CISS sequences and
      contrast-enhanced MPRAGE sequences in 100% of images. The landmarks that proved
      useful to identify the cisternal segment of the 12th cranial nerve included the
      hypoglossal trigone, preolivary sulcus, and 12th nerve root sleeve. Neurovascular
      contact was identified in 61% of root bundles. The roots were distorted in 44% of
      these contacts. CONCLUSIONS: The contrast-enhanced 3D CISS sequence consistently
      displayed the cisternal segment as well as the canalicular segments of the
      hypoglossal nerve and is, therefore, the best sequence to visualize the complete
      cranial course of this nerve. Landmarks such as the 12th nerve sleeves can assist
      in the identification of this nerve.

PMID- 12066915
TI  - Neuromuscular choristoma of the sciatic nerve. Case report.
AB  - The authors report the findings of a neuromuscular choristoma of the sciatic
      nerve in an otherwise healthy 18-year-old man who presented with sensorimotor
      symptoms and deformities of the right leg and foot. Only a few cases of this rare
      tumor, also known as "neuromuscular hamartoma" or "benign triton tumor," have
      been reported in the surgical literature. The authors discuss the clinical
      presentation, radiological findings, pathological diagnosis, and surgical
      rationale for this case and review the associated literature.

PMID- 12066916
TI  - Primary burkitt lymphoma of the brain in an immunocompetent patient. Case report.
AB  - Primary central nervous system (CNS) lymphoma is rare and is most often seen in
      immunodeficient patients. The majority of these tumors are the non-Hodgkin type
      and are high grade. Primary Burkitt lymphoma of the CNS in immunocompetent
      individuals has rarely been reported. The authors treated a 49-year-old woman who
      presented with left-sided weakness that had lasted 1.5 months. Magnetic resonance
      imaging revealed an oval mass in the left parietal region. with central necrosis
      and peripheral edema, and no attachment to the leptomeninges or ependyma.
      Pathological examination yielded a diagnosis of typical Burkitt lymphoma. Six
      months postoperatively, the patient is ambulatory and has improving neurological
      signs. This is a typical case of primary Burkitt lymphoma of the brain in an
      immunocompetent patient, which is a very rare event. The imaging pattern of the
      lesion is not typical of brain lymphomas and can result in an incorrect
      preoperative diagnosis of other brain tumors, such as glioblastoma multiforme.
      The patient's treatment and follow-up review are discussed.

PMID- 12066917
TI  - Tunneled lumbar drain. Technical note.
AB  - The authors report a simple and rapid procedure for tunneling a lumbar drain
      subcutaneously to facilitate chronic cerebrospinal fluid (CSF) drainage. A
      standard lumbar puncture (LP) is performed with a large-bore Tuohy needle (14- to
      16-gauge), the drainage catheter is advanced into the subarachnoid space, and the
      needle is removed. The free Tuohy needle is then passed from a lateral position
      and brought out through the initial LP site. The free catheter is fed through the
      needle, and the needle is removed. The drain is attached to an external drainage
      bag in the usual manner. The authors have found this method particularly useful
      in some skull base and spinal surgical applications in which longer term
      continuous CSF drainage is desired.

PMID- 12066918
TI  - Tissue resonance analysis; a novel method for noninvasive monitoring of
      intracranial pressure. Technical note.
AB  - A number of noninvasive methods used to measure intracranial pressure (ICP) have
      been proposed in the literature. For a variety of reasons, however, none of these
      have displayed significant practical applicability. The authors describe their
      development of a new, computerized, portable device based on tissue resonance
      analysis (TRA) technology for the noninvasive monitoring and measurement of ICP.
      In response to the heart beat, the soft tissue and fluid compartments of the
      brain each exhibit characteristic vibration and mechanical resonant responses
      that radiate through the organs and tissues of the body. Patterns of vibration
      and mechanical resonance of various body organs and tissues are different and
      provide the possibility of extracting new and specific information in a
      noninvasive fashion. According to the TRA approach, ICP is dependent on the value
      of the dominant secondary (mechanical) resonance level of brain tissue. By
      digitally processing a reflected ultrasound signal (by using a concave
      ultrasonography probe with a carrier frequency of 1 MHz) from the third
      ventricle, the authors obtained a digital high-resolution echopulsogram, which
      visually is equivalent to ICP waves that are obtained invasively. The fast
      Fourier relationship of electrocardiogram and echopulsogram waves allowed the
      derivation of the secondary mechanical resonance levels. The authors developed a
      formula for a quantitative, noninvasive measurement of ICP, which uses
      information regarding multiple components of the intracranial space-both
      mechanical (secondary resonance) and physiological (time required for transfer of
      arterial blood to venous blood through brain tissue)-and the relationship between
      these components. A comparison of invasive and noninvasive ICP measurements was
      made during blinded trials in 40 patients with various diseases of the central
      nervous system, and ranges of ICP were measured from I to 66 mm Hg. The ICP
      values obtained using the two methods were highly correlated (r = 0.99), without
      a statistically significant difference between simultaneously obtained readings
      (p = 1). By using an integrative approach that reflects all components of the
      intracranial compartment, TRA allows for accurate noninvasive recordings of ICP.
      This method has significant advantages over other noninvasive technologies
      reported to date.

PMID- 12066919
TI  - Neuroendoscopic identification of a basilar artery tip aneurysm in the third
      ventricle. Case illustration.

PMID- 12066920
TI  - George J. Heuer: forgotten pioneer neurosurgeon at the Johns Hopkins Hospital.
AB  - George J. Heuer was a pioneer in neurosurgery at The Johns Hopkins Hospital in
      the early 20th century; he trained under Harvey Cushing and acted as a mentor to
      Walter Dandy. In his early career, Heuer focused on research and clinical work in
      the field of neurosurgery and temporarily led the neurosurgery section at Johns
      Hopkins. One of his most important contributions to neurosurgery was the modern
      frontotemporal craniotomy. This elegant craniotomy, which initially was used to
      approach chiasmal tumors, developed into the modern frontosphenotemporal
      craniotomy, which neurosurgeons use to approach numerous tumors as well as most
      aneurysms. Although Dandy is frequently credited with inventing this operation.
      his article detailing the new approach clearly attributes its origin to Heuer,
      who was serving in World War I when the new technique was presented. Although he
      had hoped to lead the neurosurgical section at Johns Hopkins permanently, he
      returned from military service to find that Dandy had been appointed to this
      position. Heuer subsequently advanced to a distinguished career in general
      surgery as the chairman of surgery at two institutions, and was known for his
      contributions to surgical education. Throughout his academic years, Heuer
      continued to operate on the nervous system and to perform spinal cord and
      peripheral nerve surgery. He played an important role along with Cushing and
      Dandy in the creation of neurosurgery as a specialty, but he is rarely given
      credit for this accomplishment. The authors describe Heuer's contributions to
      neurosurgery as well as his distinguished surgical career.

PMID- 12066921
TI  - R. Glen spurling: surgeon, author, and neurosurgical visionary.
AB  - Doctor Roy Glenwood Spurling (1894-1968) stands as a prominent figure in the
      field of neurosurgery. His innovative contributions have left an indelible mark,
      particularly in the treatment of lumbar and cervical intervertebral disc diseases
      and peripheral nerve injuries. He was instrumental in founding the Harvey Cushing
      Society (later renamed the American Association of Neurological Surgeons) and the
      American Board of Neurological Surgery. Spurling was a major participant in the
      military during World War II; he was stationed at Walter Reed Hospital and in the
      European Theater, and later became well known for his care of General George S.
      Patton. Glen Spurling is a role model to a younger generation of neurosurgeons
      for his tireless effort toward the advancement of neurosurgery.

PMID- 12066922
TI  - Autoregulation-oriented strategy.

PMID- 12066923
TI  - Transsphenoidal surgery.

PMID- 12066924
TI  - Propofol.

PMID- 12066925
TI  - Propofol.

PMID- 12066926
TI  - Deep brain stimulation.

PMID- 12066927
TI  - Deep brain stimulation.

PMID- 12066928
TI  - Intraoperative angiography.

PMID- 12066929
TI  - Anterior paraclinoid aneurysms.

PMID- 12066930
TI  - Neurovascular compression.

PMID- 12066931
TI  - Vasospasm.

PMID- 12066932
TI  - Routine intraoperative angiography during aneurysm surgery.
AB  - OBJECT: The routine use of intraoperative angiography as an aid in the surgical
      treatment of aneurysms is uncommon. The advantages of the ability to visualize
      residual aneurysm or unintended occlusion of parent vessels intraoperatively must
      be weighed against the complications associated with repeated angiography and
      prolonged vascular access. The authors reviewed the results of their routine use
      of intraoperative angiography to determine its safety and efficacy. METHODS:
      Prospectively gathered data from all aneurysm cases treated surgically between
      January 1996 and June 2000 were reviewed. A total of 303 operations were
      performed in 284 patients with aneurysms; 24 patients also underwent
      postoperative angiography. Findings on intraoperative angiographic studies
      prompted reexploration and clip readjustment in 37 (11%) of the 337 aneurysms
      clipped. Angiography revealed parent vessel occlusion in 10 cases (3%), residual
      aneurysm in 22 cases (6.5%), and both residual lesion and parent vessel occlusion
      in five cases (1.5%). When compared with subsequent postoperative imaging, false
      negative results were found on two intraoperative angiograms (8.3%) and a false
      positive result was found on one (4.2%). Postoperative angiograms obtained in
      both false-negative cases revealed residual anterior communicating artery
      aneurysms. Both of these aneurysms also subsequently rebled, requiring
      reoperation. In the group that underwent intraoperative angiography, in 303
      operations eight patients (2.6%) suffered complications, of which only one was
      neurological. CONCLUSIONS: In the surgical treatment of intracranial aneurysms,
      the use of routine intraoperative angiography is safe and helpful in a
      significant number of cases, although it does not replace careful intraoperative
      inspection of the surgical field.

PMID- 12066934
TI  - Routine induction of labour at 41 weeks gestation: nonsensus consensus.

PMID- 12066933
TI  - Intraoperative angiography during aneurysm surgery: a prospective evaluation of
      efficacy.
AB  - OBJECT: Indications for intraoperative angiography during aneurysm surgery remain
      unclear. To define its use, the authors report the results of a prospective study
      in which this modality was used in all patients undergoing surgery for
      intracranial aneurysms. METHODS: Intraoperative angiography was performed
      prospectively in the surgical treatment of 517 consecutive aneurysms regardless
      of the lesion's location, size, or complexity. In 64 (12.4%) of 517 aneurysms
      intraoperative angiography findings prompted a change in surgical treatment.
      Residual aneurysm (47%) was the most frequent finding leading to clip revision.
      In 44% of cases, intraoperative angiography revealed vessel compromise. Surgery
      for aneurysms of the proximal internal carotid artery (ICA) was the most
      frequently altered, with lesions located at the superior hypophyseal artery (SHA)
      and clinoidal region having the highest revision rates, eight (40%) of 20 and
      eight (44%) of 18, respectively. Aneurysm size predicted the need for revision;
      giant aneurysms (> 24 mm) underwent revision in nine (29%) of 31 cases, whereas
      large aneurysms (15-24 mm) were revised in 12 (22%) of 54 cases. In a
      multivariate logistic regression model, factors related to increased revision
      rates included the SHA and clinoidal locations, as well as giant and large size.
      Ninety-five patients underwent both intraoperative and postoperative angiography.
      Five discrepancies were noted (95% accuracy); four were flow-related and one
      involved a previously unrecognized residual aneurysm. Complications attributable
      to intraoperative angiography occurred in 0.4% of cases. CONCLUSIONS: Proximal
      ICA location and large aneurysm size significantly predicted revision of surgery
      following intraoperative angiography. Unexpected findings, even in less complex
      locations, are frequently identified on intraoperative angiography. Low
      complication rates, high accuracy, and the unexpected need for clip readjustments
      favor a more widespread use of intraoperative angiography.

PMID- 12066935
TI  - In praise of Kielland's forceps.

PMID- 12066936
TI  - Guidelines on using guidelines.

PMID- 12066937
TI  - What is a reasonable time from decision-to-delivery by caesarean section?
      Evidence from 415 deliveries.
AB  - OBJECTIVE: To determine how long it takes from the decision to achieve delivery
      by non-elective caesarean section (DDI), the influences on this interval, and the
      impact on neonatal condition at birth. DESIGN: Twelve months prospective data
      collection on all non-elective caesarean sections. METHODS: Prospective
      collection of data relating to all caesarean sections in 1996 in a major teaching
      hospital obstetric unit was conducted, without the knowledge of the other
      clinicians providing clinical care. Details of the indication for section, the
      day and time of the decision and the interval till delivery were recorded as well
      as the seniority of the surgeon, and condition of the baby at birth. RESULTS: The
      mean time from decision-to-delivery for 100 emergency intrapartum caesarean
      sections was 42.9 minutes for fetal distress and 71.1 minutes for 230 without
      fetal distress (P < 0.0001). For 22 'crash' sections the mean time from decision
      to-delivery was 27.4 minutes; for 13 urgent antepartum deliveries for fetal
      reasons it was 124.7 minutes and for 21 with maternal reasons it was 97.4
      minutes. The seniority of the surgeon managing the patient did not appear to
      influence the interval, nor did the time of day or day of the week when the
      delivery occurred. Intrapartum sections were quicker the more advanced the
      labour, and general anaesthesia was associated with shorter intervals than
      regional anaesthesia for emergency caesarean section for fetal distress (P <
      0.001). Babies born within one hour of the decision tended to be more acidaemic
      than those born later, irrespective of the indication for delivery. Babies tended
      to be in better condition when a time from decision-to-delivery was not recorded
      than those for whom the information had been recorded. CONCLUSION: Fewer than 40%
      intrapartum deliveries by caesarean section for fetal distress were achieved
      within 30 minutes of the decision, despite that being the unit standard. There
      was, however, no evidence to indicate that overall an interval up to 120 minutes
      was detrimental to the neonate unless the delivery was a 'crash' caesarean
      section. These data thus do not provide evidence to sustain the recommendation of
      a standard of 30 minutes for intrapartum delivery by caesarean section.

PMID- 12066938
TI  - The decision-to-delivery interval for emergency caesarean section: is 30 minutes
      a realistic target?
AB  - OBJECTIVE: To evaluate whether a 30-minute decision-to-delivery interval is a
      realistic target for emergency caesarean section. DESIGN: An audit of all
      emergency caesarean sections over five separate periods. SETTING: A district
      general hospital. PARTICIPANTS: Five groups of women (343 women) with an
      indication for emergency caesarean section. METHODS: Following an initial survey,
      a structured time sheet was introduced, followed by four other surveys to
      complete the audit cycle. MAIN OUTCOME MEASURE: The proportion of caesarean
      sections where the decision-to-delivery interval was achieved within 30 minutes.
      The reasons for delay. RESULTS: In the first survey of 73 emergency caesarean
      sections, the time to deliver the infant exceeded 30 minutes in 47 women (64%).
      The main sources of delay were transferring the women to the operating theatre
      and starting the anaesthetic. After the introduction of a structured time sheet,
      there was an improvement with each survey, but the target of 30 minutes was
      reached in only 71% of caesarean sections in the final survey. CONCLUSIONS: The
      introduction of a time sheet can improve the decision-to-delivery interval for
      emergency caesarean section; however, a universal standard of 100% in 30 minutes
      is unrealistic.

PMID- 12066939
TI  - A double-blind randomised controlled trial of continuous oxygen therapy for
      compromised fetuses.
AB  - OBJECTIVE: To investigate the effect of chronic oxygen therapy in fetuses with
      absent end diastolic flow in the umbilical artery assessed by doppler analysis at
      24-30 weeks of gestation. DESIGN: A double-blind, randomised control trial was
      performed with patients blindly allocated to receive humidified oxygen or
      humidified air. SETTING: A tertiary referral hospital in South Africa.
      PARTICIPANTS: Thirty-two women who presented between 24 and 30 weeks of gestation
      with a confirmed finding of absent end diastolic flow in the umbilical artery.
      METHODS: After randomisation patients were allocated to receive a 40% mixture of
      humidified oxygen or humidified air from uniform coloured gas cylinders which
      were marked either 'a' or 'b' All women received betamethasone from 27 weeks of
      gestation on a weekly basis. Cardiotocographs were used from 28 weeks of
      gestation; after 28 weeks of gestation an amniocentesis was considered to confirm
      fetal maturity. Women were expected to breath the allocated gas continuously
      apart from meals and visits to the toilet. MAIN OUTCOME MEASURES: Survival of the
      fetus was the main outcome measure with secondary outcome measures documenting
      improvement in the fetal condition in utero. RESULTS: There were 16 women
      randomised to receive oxygen and 16 to receive air. There were nine survivors in
      the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95%
      confidence interval 0.7-3.2). There was a nonsignificant increase in mean
      birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a
      nonsignificant increase in mean duration of treatment in the oxygen group (12.8
      days vs 10.4 days). CONCLUSION: This study did not demonstrate that chronic
      oxygen therapy provides any benefits to compromised fetuses between 24 and 30
      weeks of gestation. Larger studies with sufficient power are necessary to assess
      whether oxygen therapy can reduce perinatal mortality by a clinically useful
      amount in this group of patients.

PMID- 12066940
TI  - Does fetal tracheal fluid flow during fetal breathing movements change before the
      onset of labour?
AB  - OBJECTIVE: To examine changes in intra-tracheal fluid flow parameters during
      fetal breathing movements throughout the second half of pregnancy in the normally
      developing human fetus. DESIGN: Prospective cross-sectional study. SETTING: Fetal
      medicine unit at the Charite University Hospital in Berlin. METHODS: Assessment
      of tracheal fluid flow was attempted in 340 healthy fetuses (GA 20-40 weeks) in
      which fetal breathing movements were seen by B-mode scan. Colour Doppler was
      applied to visualise the tracheal fluid flow, followed by spectral Doppler to
      record the velocity waveforms. The records of 53 fetuses divided into five
      gestational age groups (20-23, 24-27, 28-31, 32-35 and 36-40 weeks of gestation)
      containing 40 or more continuous breathing cycles (inspiration and expiration)
      were considered for analysis. Only regular breathing phases were examined and the
      volume obtained by integration of the tracheal fluid flow displaced during fetal
      breathing movements was calculated. RESULTS: The intra-tracheal flow volume moved
      during inspiration (Vi) and expiration (Ve) increased until 36 weeks of gestation
      after which there was a flattening until term. This suggests either a reduction
      of lung liquid production or a diminished lung liquid volume. The median
      difference between Vi and Ve was positive in the first four age groups and
      negative in the last one suggesting that, in mature fetuses, the effect of fetal
      breathing movements no longer results in an influx. CONCLUSIONS: Our data
      demonstrate a modification in fetal behaviour that manifests itself during the
      last four weeks before birth and has the potential to reduce lung liquid volume.

PMID- 12066941
TI  - The effect of fundal pressure manoeuvre on intrauterine pressure in the second
      stage of labour.
AB  - OBJECTIVE: To investigate the relationship between intrauterine pressure and the
      application of a standardised fundal pressure manoeuvre, and to determine the
      maternal, fetal and labour characteristics that modulate the relationship.
      DESIGN: Prospective measurement of intrauterine pressure during the second stage
      of labour. SETTING: North American university hospital. POPULATION: Forty full
      term women in spontaneous labour were studied during the second stage. Each woman
      acted as her own control. All women laboured with requested epidural analgesia.
      METHODS: A fundal pressure manoeuvre was performed so as to standardise the level
      of force and the surface area of application. Intrauterine pressure was measured
      using a sensor-tip catheter. Five interventions were analysed: 1. valsalva during
      a uterine contraction; 2. fundal pressure and valsalva during a contraction; 3.
      fundal pressure during a contraction without valsalva; 4. fundal pressure in the
      absence of uterine contractions; and 5. valsalva in the absence of uterine
      contractions. RESULTS: Women in the second stage of labour transiently increased
      their expulsive force (as reflected by intrauterine pressure) by 86% of their
      baseline contraction using valsalva and fundal pressure simultaneously. The
      efficiency by which both contraction-enhancing manoeuvres increased intrauterine
      pressure was directly related to gestational age and inversely related to
      myometrial thickness. CONCLUSION: Fundal pressure applied under controlled
      conditions significantly increases intrauterine pressure in some, but not all
      women. Simultaneous measurement of intrauterine pressure, to maintain feedback
      during application will create a 'controlled environment' for the obstetrician
      and reassurance that this manoeuvre can be applied in a controlled fashion.
      Future delineation of the group of women that could benefit from fundal pressure,
      as well as the group that is refractory is essential to avoid unnecessary or
      delayed operative interventions.

PMID- 12066942
TI  - Possible association between amniotic fluid micro-organism infection and
      microflora in the mouth.
AB  - OBJECTIVE: To determine whether oral bacteria are found in the amniotic cavity.
      DESIGN: Laboratory based analysis of clinical samples. SETTING: Royal London
      Hospital, Whitechapel. POPULATION: Forty-eight women attending for elective
      caesarean section. METHODS: Dental plaque, a high vaginal swab, amniotic fluid
      and chorioamnion tissue were taken from women with intact membranes. MAIN OUTCOME
      MEASURES: Samples were investigated using culture and microscopy for the presence
      of microorganisms. Amniotic fluid was analysed by polymerase chain reaction (PCR)
      for the presence of the ubiquitous 16S rRNA gene specific to most eubacteria.
      Samples were analysed using PCR genus and species specific primers directed to
      bacterial taxa found as part of the normal oral microflora (Streptococcus spp.
      and Fusobacterium nucleatum). Levels of prostaglandin E2 and cytokines were
      measured in amniotic fluid. RESULTS: Amniotic fluid was positive for universal
      bacteria PCR, Streptococcus spp. PCR and F. nucleatum PCR in 34/48, 20/48 and
      7/48 of cases, respectively. Streptococcus spp. and F. nucleatum were cultured
      from the dental plaque, vagina and amniotic fluid of 48/48, 14/48, 0/48 and
      29/48, 6/48, 0/48 subjects, respectively. A significant association was found
      between detection of microbial DNA (universal and F. nucletum) and complications
      in previous pregnancies including miscarriage, intrauterine death, neonatal
      death, preterm delivery and premature rupture of membranes (P < 0.05 and P <
      0.01, respectively). Prostaglandin E2 and cytokine levels, with the exception of
      IL-1alpha, were not significantly different between women with and without
      evidence of infection. CONCLUSIONS: The results indicate that Streptococcus spp.
      and F. nucleatum in the amniotic fluid may have an oral origin.

PMID- 12066943
TI  - Histologic chorioamnionitis and umbilical serum levels of pro-inflammatory
      cytokines and cytokine inhibitors.
AB  - OBJECTIVE: To study 1. whether leucocyte infiltration in placenta tissues is
      associated with elevated umbilical serum levels of inflammatory mediators, and 2.
      whether leucocyte infiltration in the presence of neonatal disease is associated
      with additional increase in mediator levels. SETTING: University hospital.
      POPULATION: Two groups of women with either normal delivery (n = 82) or delivery
      complicated by prolonged rupture of the membranes, clinical signs of intrauterine
      infection or preterm labour (n = 139). METHODS: Umbilical cord blood and placenta
      tissues were collected after delivery. Placentas were classified as non-inflamed
      (i.e. without leucocyte infiltration, n = 74), or as mild (n = 84), or severe
      chorioamnionitis (n = 63). Mediator levels were compared between groups. RESULTS:
      Severe chorioamnionitis was associated with elevated levels of tumour necrosis
      factor (TNF)alpha, interleukin (IL)-1beta, IL-6, IL-8, soluble TNF receptor p55
      and p75, IL-1 receptor antagonist (IL-IRA), and C-reactive protein compared with
      non-inflamed placentas (all P < 0.05). No differences were found between mild
      chorioamnionitis and placentas without infiltration. In all, 49 babies suffered
      from various perinatal diseases, such as clinical sepsis, respiratory distress
      and asphyxia, and 172 were healthy. Severe chorioamnionitis with subsequent
      neonatal disease (n = 23) had higher levels of all mediators, except IL-1beta and
      C-reactive protein, than severe chorioamnionitis without neonatal disease (n =
      40, all P < 0.01), but severe chorioamnionitis was also accompanied by a more
      intense and widely distributed leucocyte infiltration when neonatal disease
      developed. CONCLUSION: High grade leucocyte infiltration in placenta tissues is
      associated with elevated levels of TNFalpha, IL-1beta, IL-6, IL-8, p55, p75, IL
      IRA and C-reactive protein in umbilical serum. The presence of neonatal disease
      is associated with advanced chorioamnionitis, and highly elevated levels of both
      pro- and antiinflammatory mediators in umbilical serum.

PMID- 12066944
TI  - A deficient maternal calcium intake during pregnancy increases blood pressure of
      the offspring in adult rats.
AB  - OBJECTIVE: To assess in an animal model the effect of maternal dietary calcium
      intake during pregnancy on the blood pressure of offspring. DESIGN: Randomised
      controlled trial. SAMPLE: Ninety-eight 20-week-old female Wistar-Kyoto rats,
      giving birth to a total of 119 pups that were included in the follow up study.
      METHODS: Rats were randomised to a calcium deficient diet, a diet with the
      recommended calcium levels, or a diet with calcium content much higher than the
      recommended levels. After one month on the experimental diet they were bred.
      After birth, systolic blood pressure in the offspring was measured monthly till
      52 weeks of age. MAIN OUTCOME MEASURES: Blood pressure of the offspring. RESULTS:
      The difference in blood pressure of the offspring between the normal and low
      maternal calcium group increased 0.49 mmHg per month (95% CI 0.18 to 0.84), 0.38
      (0.07 to 0.68) between the low and high calcium group, and 0.12 (-0.20 to 0.43)
      between the normal and high calcium group. At the end of the follow up (52 weeks
      of age) blood pressure of the offspring in the deficient calcium group was 12.1
      mmHg (95% CI 8.8 to 15.4, P < 0.0001) higher than in the normal calcium group and
      7.5 mmHg (95% CI 4.4 to 10.5, P < 0.001) higher than the high calcium group.
      Blood pressure of the offspring in the high calcium group was 4.3 mmHg (95% CI
      1.0 to 7.5, P = 0.01) higher than in the normal calcium group. In a multiple
      regression model maternal calcium intake during pregnancy was the strongest
      predictor of blood pressure of the offspring during adulthood. CONCLUSIONS: This
      experiment supports previous studies in humans suggesting a link between calcium
      intake during pregnancy and blood pressure in the offspring, and provides an
      animal model to explore the mechanisms involved in such association.

PMID- 12066945
TI  - Altered vascular function in healthy normotensive pregnant women with bilateral
      uterine artery notches.
AB  - OBJECTIVES: To assess endothelial function and vascular mechanical properties in
      normotensive pregnant women with high resistance in the uteroplacental
      circulation. DESIGN: Cross-sectional prospective study. SETTING: Doppler
      ultrasound laboratory at university department of obstetrics and gynaecology
      referral centre for high risk pregnancies. PARTICIPANTS: Forty-two caucasian
      normotensive pregnant women: 23 with uncomplicated pregnancies and 19 with
      bilateral uterine artery notches. METHODS: Flow-mediated dilatation of the
      brachial artery was measured by ultrasonography at 25 gestational weeks.
      Concentrations of nitrite and nitrate in the plasma were established at 25 and 32
      gestational weeks. The elastic properties of the common carotid artery, abdominal
      aorta and popliteal artery were measured with an ultrasonic echo-tracking system.
      RESULTS: Flow-mediated dilatation at two minutes after cuff deflation was
      significantly lower in the bilateral notch group compared with the control group,
      8.3% and 13.7%, respectively (P = 0.0007). The ability to sustain vasodilatation
      was reduced in the bilateral notch group (P = 0.02). Lower values of nitrite and
      nitrate in the plasma were found at 32 gestational weeks in the bilateral notch
      group than in the control group (mean 24.76 microM/L (SD 5.6) and 30.93 microM/L
      (8.2), respectively; P = 0.008). Nitrite and nitrate levels tended to be lower in
      the bilateral notch group even at 25 gestational weeks (29.45 microM/L (8.3) and
      35.73 microM/L (11.0) in the bilateral notch and control group, respectively; P =
      0.09). There was no difference in aortic, carotid or popliteal elasticity between
      the two groups. CONCLUSIONS: Healthy normotensive pregnant women with bilateral
      uterine artery notches show impaired endothelial function, but no differences in
      vascular mechanical properties.

PMID- 12066946
TI  - A randomised study comparing a low dose of mifepristone and the Yuzpe regimen for
      emergency contraception.
AB  - OBJECTIVE: To compare 100 mg mifepristone with the standard Yuzpe regimen for
      emergency contraception. DESIGN: Randomised controlled trial. SETTING: Family
      Planning Clinic, Aberdeen. SAMPLE: One thousand women seeking emergency
      contraception within 72 hours after an episode of unprotected sexual intercourse.
      METHODS: Women were randomised to receive either 100 mg (half tablet) of
      mifepristone as a single dose or the Yuzpe regimen (two tablets each with 50
      microg ethinyloestradiol and 0.25 mg levonorgestrel, to be repeated 12 hours
      later). OUTCOME MEASURES: Crude pregnancy rates, proportion of pregnancies
      prevented, side effects and patient acceptability. RESULTS: The crude pregnancy
      rates (95% CI) for the Yuzpe regimen and mifepristone were 3.6% (2.3-5.7) and
      0.6% (0.2-1.8), respectively, with a significant difference between the two
      groups (RR 6.04; 95% CI 1.75-20.75). Mifepristone prevented 92% of pregnancies
      and the Yuzpe regimen preventing 56%. An increasing coitus to treatment interval
      was associated with contraceptive failure in the Yuzpe group (P = 0.03) with no
      association seen with mifepristone. Following administration of mifepristone
      24.5% and 13.1% given the Yuzpe regimen had a delayed period (RR 2.14; 95% CI
      1.46-3.15). Overall, mifepristone was better tolerated than the Yuzpe regimen
      with significantly fewer side effects. More women were satisfied (P < 0.0001)
      with mifepristone as an emergency contraceptive and would recommend it to a
      friend (P = 0.02). CONCLUSION: Mifepristone administered in a 100 mg dose is a
      highly effective post-coital contraceptive with high patient acceptability and
      fewer side effects compared with the standard Yuzpe regimen. Delay in the onset
      of menstruation did not decrease patient acceptability.

PMID- 12066947
TI  - A randomised placebo-controlled trial of vaginal misoprostol for cervical priming
      before hysteroscopy in postmenopausal women.
AB  - OBJECTIVE: To investigate the effectiveness of misoprostol given vaginally for
      cervical priming before hysteroscopy in postmenopausal women. DESIGN: Double
      blind randomised controlled study. SETTING: Regional hospital, Hong Kong.
      PARTICIPANTS: One hundred women with postmenopausal bleeding scheduled for
      hysteroscopy from October 1998 to September 2001 were randomly assigned to
      receive either misoprostol or placebo vaginally before the operation. MAIN
      OUTCOME MEASURES: The number of women requiring cervical dilatation, outcome of
      hysteroscopy and side effects of the medication were assessed. RESULTS: Forty
      eight women receiving misoprostol and 48 women receiving placebo were compared.
      The mean degree of endocervical diameter estimated by Hegar's dilator was similar
      between the treatment group and the control group. A similar number of women in
      the treatment group and the control group required cervical dilatation. The
      operative times for both groups were similar. The incidence of side effects was
      comparable in both groups. The most common side effects for misoprostol were
      febrile episodes and diarrhoea. There was no cervical tear nor uterine
      perforation encountered in both groups. The mean duration of hospital stay in
      both groups were similar. Subanalysis of results were similar in women receiving
      vaginal medication at least five hours before the operation. CONCLUSION: Vaginal
      misoprostol was not shown to reduce the need for cervical dilatation in
      postmenopausal women. It cannot convert diagnostic hysteroscopy from a hospital
      procedure into an office one in postmenopausal women with tight cervical os.

PMID- 12066948
TI  - Short term complications of the tension free vaginal tape operation for stress
      urinary incontinence in women.
AB  - OBJECTIVE: To assess the prevalence of intra- and post-operative complications
      with the tension free vaginal tape operation for female urinary incontinence.
      DESIGN: Non-control case series. SETTING: University Hospital. POPULATION: One
      hundred and seventy-seven operations on women who were diagnosed urodynamically
      to have genuine stress incontinence. In 26 cases (15%) there was symptomatic urge
      incontinence. MAIN OUTCOME MEASURES: Intra- and post-operative complications in
      relation to individual surgeons and mode of anaesthesia (local or spinal), and
      continence at short term follow up. RESULTS: Bladder or urethral perforation
      occurred in 26 cases (15%) and three operations were abandoned for these reasons.
      A failure to void after the first 24 hours was registered in 35 (20%); 21 (12%)
      had to undergo urethral dilatation while five patients (2.8%) had persistent
      urinary retention which required excision of the sling. These problems were
      significantly associated to the experience of surgeon. In seven cases (4%)
      haemorrhage required intravaginal tamponade. In three (1.7%) sling rejection
      occurred post-operatively. When followed up six to eight weeks post-operatively,
      154 patients (88%) reported subjective cure, 21 (11%) significant improvement and
      two (1%) no improvement. The use of spinal anaesthesia increased the frequency of
      peroperative bladder perforation but affected neither the incidence of post
      operative bladder obstruction nor the outcome at follow up. CONCLUSIONS: This
      study identifies short term complications which relate partly to the experience
      of the individual surgeon. Nevertheless the 88% subjective cure rate was
      independent of these factors.

PMID- 12066949
TI  - Placental massive perivillous fibrin deposition associated with antiphospholipid
      antibody syndrome.
AB  - We present three pregnancies in which massive perivillous fibrous deposition
      (MPVFD) and maternal floor infarction (MFI) occurred in patients with primary
      antiphospholipid antibody syndrome (PAPS) attending a recurrent miscarriage
      clinic, and who were treated with low dose aspirin and heparin. We hypothesise
      that PAPS may be a predisposing factor to the development of this condition. The
      increased prevalence of late pregnancy complications in PAPS patients with a
      history of early miscarriage suggests that aspirin and heparin therapy does not
      eradicate the underlying pathological process but merely reduces the severity.
      Therefore, untreated early pregnancy losses may be converted into treated
      pregnancies with late antenatal complications. Some patients with PAPS may
      therefore be prone to suffer either the previously reported complications of the
      uteroplacental vasculature, such as pre-eclampsia, and/or specific complications
      related to the environment of the intervillus space, such as MPVFD/MFI.

PMID- 12066951
TI  - Influence of omental biopsy on adjuvant treatment field in clinical Stage I
      endometrial carcinoma.
AB  - In this study to assess the role of omental biopsy in the diagnosis of
      extrapelvic disease, data from 100 consecutive women with clinical Stage I
      endometrial cancer undergoing primary surgical treatment in our institution were
      analysed: 80 women had an omental biopsy, 20 did not, and six had adenocarcinoma
      in the omentum. No obvious morbidity attributable to this rapid and easily
      performed surgical procedure was recorded. We conclude that visual inspection and
      palpation of the omentum at the time of abdominal surgery for endometrial
      carcinoma is worthwhile and advisable. In addition, adopting a protocol of
      histological assessment upstaged a further two cases of this series. These data
      suggest that this technique might influence the prescription of adjuvant pelvic
      radiation in approximately one in 10 women currently considered for such therapy,
      as disease can be easily documented as having extended beyond the conventional
      radiotherapy field.

PMID- 12066950
TI  - Polymorphisms in various coagulation genes in black South African women with
      placental abruption.
AB  - This pilot study examined Factor V Leiden (R506Q), prothrombin (20210G-->A),
      thrombomodulin (A455V) and MTHFR (677C-->T) in 100 Zulu-speaking black South
      African women with placental abruption and 217 controls. The Factor V Leiden and
      prothrombin variant gene alleles were not detected in either patient or control
      groups. The thrombomodulin polymorphic variant was not seen in the patient group
      but three heterozygotes (1%) were found in the controls. No homozygotes for the
      MTHFR T677 variant were detected in the patients but two (1%) were noted in the
      controls; the normal and heterozygote genotype and allele frequencies for this
      polymorphism were similar in the two groups.

PMID- 12066952
TI  - Persistent infection with human papillomavirus following the successful treatment
      of high grade cervical intraepithelial neoplasia.
AB  - In a need case-control study, we identified women who were successfully treated
      for CIN 3. Cases had biopsy proven recurrence, whilst controls remained disease
      free for at least five years. One hundred and seventy-two women were beta-globin
      positive at diagnostic and at six-month post-treatment smear (90 controls and 82
      cases). Thirty-nine cases (47.6%) were HPV16/18 positive at biopsy or follow up
      smear and 14 (17.1%) of 82 were positive at both. Of the controls, 37 (41.1%)
      were HPV positive at biopsy or smear with (3.3%) positive at both. The unadjusted
      OR associated with being HPV positive at both points compared to being HPV
      negative at both was 8.0 (95% CI 2.13-30.37). The persistence of HPV 16/18
      infection following the confirmed eradication of CIN is a highly significant risk
      factor for recurrence.

PMID- 12066953
TI  - Congenital paraplegia. A complication of multifetal pregnancy reduction?

PMID- 12066955
TI  - Persistent retained placenta percreta: methotrexate treatment and Doppler flow
      characteristics.

PMID- 12066954
TI  - Uterine torsion and ischaemia of one horn of a bicornute uterus: a rare cause of
      failed second trimester termination of pregnancy.

PMID- 12066956
TI  - Elevated hCG and a high proportion of hCGbeta in serum preceding the diagnosis of
      trophoblastic disease by seven months.

PMID- 12066957
TI  - Culdoscopy to examine the contour of the uterus before hysteroscopic metroplasty
      for uterine septum.

PMID- 12066958
TI  - Point-of-care versus laboratory monitoring of patients receiving different
      anticoagulant therapies.
AB  - STUDY OBJECTIVE: To compare point-of-care and standard hospital laboratory assays
      for monitoring patients receiving single or combination anticoagulant regimens.
      DESIGN: Prospective analysis. SETTING: Nursing units and clinics at a large,
      community hospital. PATIENTS: One hundred fifty patients receiving anticoagulants
      for cardiac, vascular, orthopedic, or cancer indications. Thirty patients were
      enrolled into each treatment group: warfarin, enoxaparin, heparin, warfarin plus
      enoxaparin, and warfarin plus heparin. INTERVENTION: Capillary and venous blood
      samples were collected once in each patient for simultaneous measurement of
      international normalized ratio (INR) and activated partial thromboplastin time
      (aPTT) by both assays. MEASUREMENTS AND MAIN RESULTS: Mean differences in paired
      INR and paired aPTT by point-of-care and standard assays were small, but 95%
      confidence intervals were wide. The INR differences were greater for the warfarin
      plus heparin group than for the warfarin group or warfarin plus enoxaparin group;
      clinical decision agreement was 47% for warfarin plus heparin, 73% for warfarin,
      and 93% for warfarin plus enoxaparin. The aPTT difference was greater for the
      warfarin plus heparin than for the heparin group; however, clinical decision
      agreement, 67% and 70%, respectively, was similar. CONCLUSIONS: Point-of-care
      methods showed limited agreement with standard hospital laboratory assays of
      coagulation for all treatment groups. For INR values, significantly greater
      disagreement was noted between the assay methods for the warfarin plus heparin
      group compared with the warfarin group, but the agreement was similar for the
      warfarin and warfarin plus enoxaparin groups. Our data indicate that the point-of
      care assays should not be considered interchangeable with standard laboratory
      assays.

PMID- 12066959
TI  - Population pharmacokinetic modeling of pyrazinamide in children and adults with
      tuberculosis.
AB  - STUDY OBJECTIVE: To determine population pharmacokinetic parameters of
      pyrazinamide after multiple oral doses given to children and adults with
      tuberculosis. DESIGN: Prospective, multiple-dose population pharmacokinetic
      study. SETTING: Five hospitals in the United States. PATIENTS: Sixty-seven adults
      and 23 children with active tuberculosis. INTERVENTION: The 90 patients received
      multiple oral doses of pyrazinamide as part of their treatment, based on the best
      clinical judgment of the attending physicians and in keeping with standard
      clinical practices at each institution. The patients also received other
      antituberculosis drugs empirically or based on in vitro susceptibility data.
      MEASUREMENTS AND MAIN RESULTS: Serum samples were collected over 12 hours after
      dosing and were assayed with a validated gas chromatography assay with mass
      selective detection. Concentration-time data were analyzed by using population
      methods. Pyrazinamide concentrations increased linearly with increasing oral
      doses (185-3550 mg). Median maximum serum concentration values were 41.0
      microg/ml with daily dosing and 66.1 microg/ml with larger, twice-weekly dosing.
      Incomplete (18%) or delayed (30%) absorption was more common in children than in
      adults (1% for each). Pharmacokinetic parameters of pyrazinamide were independent
      of human immunodeficiency virus status and patient demographics, except for body
      weight. Population elimination half-life values in pediatric and adult patients
      were 3.5 and 6.0 hours, respectively. Median volume of distribution (L/kg) was
      32% larger in children, and median clearance (L/hr/kg) was 106% larger in
      children, with a resultant median half-life 43% shorter in children. CONCLUSION:
      Pyrazinamide concentrations and most pharmacokinetic parameters were comparable
      to those previously published. Apparent half-life was somewhat shorter than that
      in previous reports. Compared with adults, absorption of pyrazinamide in children
      appeared more likely to be incomplete or delayed.

PMID- 12066960
TI  - Itraconazole and fluconazole and certain rare, serious adverse events.
AB  - STUDY OBJECTIVE: To determine rates of drug-induced, rare, serious adverse events
      affecting the liver, kidneys, skin, or blood, occurring within 45 days of
      completing a prescription or refill for itraconazole or fluconazole. DESIGN:
      Population-based follow-up study SETTING: United Kingdom-based General Practice
      Research Database. PATIENTS: Total of 54,803 users of either fluconazole or
      itraconazole. MAIN RESULTS: Four patients were identified with illnesses for
      which a drug-induced etiology could not be ruled out; one with an elevated liver
      function test while taking itraconazole, one with thrombocytopenia, one with
      neutropenia, and one with an abnormal liver function test just after receiving
      fluconazole. For itraconazole the rate was 3.2/100,000 prescriptions (95%
      confidence interval [CI] 0.6-17.9) for serious, adverse liver events; for
      fluconazole 2.8/100,000 prescriptions (95% CI 0.8-10.3) for serious, adverse
      blood events and 1.4/100,000 prescriptions (95% CI 0.25-8.2) for serious, adverse
      liver events. CONCLUSION: Itraconazole and fluconazole do not commonly cause
      rare, serious adverse events affecting the liver, kidneys, skin, or blood.

PMID- 12066961
TI  - Limited tolerability of levofloxacin and pyrazinamide for multidrug-resistant
      tuberculosis prophylaxis in a solid organ transplant population.
AB  - STUDY OBJECTIVE: To determine the long-term tolerability of prophylactic
      administration of pyrazinamide and levofloxacin in patients possibly exposed to
      multidrug-resistant tuberculosis (MDRTB) after undergoing solid organ
      transplantation. DESIGN: Retrospective analysis. SETTING: Community outpatient
      clinic. PATIENTS: Forty-eight recipients of solid organ transplants beginning
      prophylaxis for MDRTB during August 1999 after possible exposure to a single
      index case of multidrug-resistant Mycobacterium tuberculosis within our community
      INTERVENTION: Prophylaxis consisted of pyrazinamide 30 mg/kg/day plus
      levofloxacin 500 mg/day, administered for 1 year. MEASUREMENTS AND MAIN RESULTS:
      Thirteen (27.1%) of the 48 patients completed therapy; 27 (56.3%) discontinued
      therapy within 4 months due to adverse drug events. Gastrointestinal intolerance
      was the major adverse event resulting in early discontinuation. CONCLUSION:
      Prophylaxis of MDRTB with levofloxacin and pyrazinamide was associated with
      limited tolerability due to the high frequency of adverse events. While we search
      for a better tolerated prophylactic regimen, close monitoring for adverse
      reactions is recommended.

PMID- 12066962
TI  - Matrix metalloproteinase inhibitors: do they have a place in anticancer therapy?
AB  - Matrix metalloproteinases (MMPs) are a family of enzymes involved in degradation
      of extracellular matrix. An imbalance between MMPs and naturally occurring MMP
      inhibitors may cause excess extracellular matrix destruction, allowing cancer
      cells to invade surrounding tissues and metastasize, and permitting angiogenesis
      to occur. Inhibition of certain key MMPs may prevent angiogenesis, tumor growth,
      invasion, and metastasis. Gelatinases MMP-2 and MMP-9 are expressed during
      carcinogenesis and angiogenesis. Synthetic MMP inhibitors were designed to target
      these enzymes and potentially prevent the tumor growth and metastases associated
      with cancer.

PMID- 12066963
TI  - Chronic hepatitis B: current and future treatment options.
AB  - Hepatitis B, a major viral infection that can lead to cirrhosis and
      hepatocellular carcinoma, is the ninth most common cause of death worldwide.
      Prevention of hepatitis B virus transmission is key to reducing the spread of
      this serious condition. Management of chronic hepatitis B requires significant
      knowledge of approved pharmacotherapeutic agents and their limitations. Today,
      agents approved by the Food and Drug Administration for this infection are
      interferon-alpha-2b and lamivudine. Newer agents are being developed and hold
      promise: adefovir, famciclovir, ganciclovir, lobucavir, entecavir, emtricitabine,
      L-deoxythymidine, clevudine, a therapeutic vaccine, and thymosin alpha-1.
      Therapeutic options for managing hepatitis infection after liver transplantation
      are also evolving. These include hepatitis B immunoglobulin and nucleoside
      analogues.

PMID- 12066964
TI  - Optimizing drug therapy in patients with cardiovascular disease: the impact of
      pharmacist-managed pharmacotherapy clinics in a primary care setting.
AB  - We evaluated the effectiveness of pharmacist-managed pharmacotherapy clinics in
      implementing and maximizing therapy with agents known to reduce the morbidity and
      mortality associated with cardiovascular disease. This was a retrospective chart
      review of 150 patients who were treated for coronary artery disease in primary
      care clinics. Appropriate treatment of hypercholesterolemia occurred in 96% of
      patients referred to a clinical pharmacy specialist, compared with 68% of those
      followed by primary care providers alone (p<0.0001). Eighty-five percent and 50%,
      respectively, achieved goal low-density lipoprotein (LDL) values below 105 mg/dl
      (p<0.0001). Appropriate therapy with aspirin or other antiplatelet or
      anticoagulant drugs was prescribed in 97% and 92%, respectively (p=0.146). As
      appropriate therapy with these agents was high in both groups, the ability to
      detect a difference between groups was limited. Among patients with an ejection
      fraction below 40%, appropriate therapy with an angiotensin-converting enzyme
      inhibitor or acceptable alternative was 89% and 69%, respectively (p<0.05).
      Twenty-seven cardiac events were documented in the clinical pharmacy group,
      versus 22 in the primary care group (p=0.475). Despite the relatively high
      percentage of patients reaching goal LDL in the primary care group, referral to
      clinical pharmacy specialists resulted in statistically significant increases in
      the number of patients appropriately treated for hypercholesterolemia and
      achieving goal LDL.

PMID- 12066965
TI  - Clinical experience of quinupristin-dalfopristin for the treatment of
      antimicrobial-resistant gram-positive infections.
AB  - Data regarding clinical administration, outcomes, and costs of quinupristin
      dalfopristin treatment in 48 patients with serious gram-positive infections in a
      large teaching hospital were analyzed retrospectively. Thirty-six patients had
      vancomycin-resistant Enterococcus faecium (VREF) infections, 10 had methicillin
      resistant Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE)
      infections, and 2 were treated empirically Overall, 67% of the patients were
      clinically cured, and 56% had bacteriologic eradication; overall response rate
      was 48%. Patients with VREF bacteremia had the highest clinical cure (82%) and
      bacteriologic eradication (73%) rates. Mortality rate was 31%, but 6 of 15
      patients who died were treated successfully with quinupristin-dalfopristin.
      Length of hospital stay was significantly shorter among patients who lived versus
      those who died (p<0.05). Similarly, the mean hospital cost/patient was
      significantly lower in patients who lived than in those who died ($35,244 vs
      $122,922). Quinupristin-dalfopristin is effective in the treatment of both VREF
      and MRSA or MRSE infections in patients who fail to respond to, or are intolerant
      of, vancomycin.

PMID- 12066967
TI  - Life-threatening isradipine poisoning in a child.
AB  - Calcium channel blockers as a group are responsible for significant morbidity and
      mortality with toxic exposures. Isradipine, a cardioselective dihydropyridine
      calcium channel blocker, rarely has been implicated, with only two reports in the
      literature of significant toxic reactions, one in an adult and another in a
      child. To our knowledge, we describe the first case of life-threatening
      isradipine poisoning in a child and provide documentation of serum drug levels.
      On arrival at the hospital, a 5-year-old girl had abdominal distention and
      bradycardia that rapidly progressed to asystole. She received 73 minutes of
      cardiopulmonary resuscitation and transvenous cardiac pacing and survived with an
      intact neurologic recovery. Serum concentrations of isradipine were 30-100 times
      those found with therapeutic use.

PMID- 12066966
TI  - Effectiveness of a pharmacist-based smoking-cessation program and its impact on
      quality of life.
AB  - We conducted a prospective, open-label trial to evaluate the effectiveness of a
      pharmacist-based, comprehensive, smoking-cessation program with 31 self-referred
      subjects. A secondary goal was to measure changes in health-related quality of
      life (HRQOL) during the cessation attempt. The program consisted of weekly, 1
      hour group sessions over 12 weeks. It incorporated nicotine replacement therapy
      (patch, gum) with extensive behavior modification counseling. Trained pharmacists
      served as program facilitators. Smoking cessation was chemically verified at 3
      and 6 months by exhaled carbon monoxide. The patients' HRQOL was measured using
      the smoking-cessation quality of life questionnaire at baseline, 2 weeks, and 1,
      2, 3, and 6 months. Chemically verified abstinence rates at 3 and 6 months were
      42% (13 patients) and 26% (8 patients), respectively. Among patients who quit,
      vitality, mental health, and self-control significantly improved during the 3
      month program. Six-month cessation rates were modest, although HRQOL improved
      within 3 months of abstinence.

PMID- 12066968
TI  - Rhabdomyolysis associated with cerivastatin: six cases within 3 months at one
      hospital.
AB  - Rhabdomyolysis is an uncommon complication associated with 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors. We observed six cases of
      cerivastatin-associated rhabdomyolysis: two patients developed acute renal
      failure requiring hemodialysis, and one patient died. Four of the patients had
      impaired renal function, and five were prescribed drugs with the potential to
      interact with cerivastatin. Also, five of the six patients presented with
      symptoms of rhabdomyolysis 3-4 weeks after starting cerivastatin therapy.

PMID- 12066969
TI  - Transient pulmonary infiltrates possibly induced by quinine sulfate.
AB  - Quinine sulfate, which has been available for many years, has not been implicated
      definitively in the development of pulmonary toxicity. A variety of adverse
      effects, however, have been reported with quinine administration. A 45-year-old
      woman with longstanding rheumatoid arthritis experienced wheezing, severe
      anxiety, breathlessness, cough, orthopnea, mild fever, chills, and pleuritic
      chest discomfort after taking a single dose of quinine for nocturnal leg cramps.
      Radiographic imaging demonstrated diffuse, bilateral pulmonary infiltrates
      suggestive of pulmonary edema. No cause other than acute quinine ingestion could
      be identified despite thorough cardiac and infectious disease evaluations.
      Clinicians should be aware of a possible association between quinine sulfate and
      pulmonary toxicity.

PMID- 12066970
TI  - Asthma exacerbation after administration of nicotine nasal spray for smoking
      cessation.
AB  - A 58-year-old man experienced an asthma exacerbation after administration of
      nicotine nasal spray for smoking cessation. His medical history was significant
      for asthma, chronic obstructive pulmonary disease, hypertension, and tobacco use
      when he was prescribed nicotine nasal spray for smoking cessation in an
      outpatient setting. Within the first 3 days of administering the spray, he
      developed wheezing, coughing, and significant shortness of breath, which required
      hospitalization. The patient was hospitalized for 48 hours and discharged with a
      diagnosis of asthma exacerbation probably related to administration of nicotine
      nasal spray. Prudent administration of nicotine nasal spray is recommended in
      patients with underlying respiratory disease. Patients should be counseled on the
      potential adverse effects of treatment and proper administration techniques in
      order to minimize these effects.

PMID- 12066971
TI  - Vancomycin-induced neutropenia in a patient positive for an antineutrophil
      antibody.
AB  - A 48-year-old man, hospitalized after experiencing subarachnoid hemorrhage
      secondary to a basilar aneurysm, received vancomycin for methicillin-resistant
      Staphylococcus aureus sepsis. He developed neutropenia 16 days after the start of
      vancomycin therapy, and his white blood cell count decreased to a nadir of 1200
      cells/mm3. Vancomycin was discontinued, and granulocyte-colony stimulating factor
      (G-CSF) therapy was begun. The patient was rechallenged with a single dose of
      vancomycin 1 g in preparation for intraarterial aneurysm coiling. His white blood
      cell count dropped to 600 cells/mm3 but returned to normal with continued G-CSF
      therapy. A diagnosis of vancomycin-induced neutropenia was considered. Subsequent
      testing by granulocyte agglutination and granulocyte immunofluorescence assays
      revealed that his serum was positive for an antigranulocyte antibody. A test for
      HLA antibody reactivity was negative. Monoclonal antibody immobilization of
      granulocyte antigens assay failed to determine the antigen specificity of his
      granulocyte antibody.

PMID- 12066972
TI  - Levofloxacin-induced toxic epidermal necrolysis in an elderly patient.
AB  - Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are mild-to-life
      threatening adverse reactions that have been described after exposure to
      fluoroquinolones. No published reports, however, exist of exfoliative disease
      after treatment with levofloxacin. A 78-year-old woman with many medical
      problems, including chronic obstructive pulmonary disease, was treated with
      parenteral levofloxacin for community-acquired pneumonia. She was discharged with
      oral levofloxacin to complete an additional 3 days of treatment as an outpatient.
      Two days after completing this regimen, the patient developed a rash with
      blistering. The rash progressed to TEN in 7 days, and she was transferred to a
      burn treatment center. She was treated with fluid resuscitation, wound dressing,
      and antibiotics. Her condition improved, and she was discharged after 22 days. To
      our knowledge, this case is the first published report of levofloxacin-induced
      TEN.

PMID- 12066973
TI  - Antimicrobial-associated acute hepatitis.
AB  - Recently, the case history of a 44-year-old woman who experienced acute hepatitis
      subsequent to therapy for chronic sinusitis was reviewed. The patient
      sequentially was administered clarithromycin, levofloxacin, amoxicillin
      clavulanate, and gatifloxacin. Her adverse events were attributed definitively to
      gatifloxacin, a surprising conclusion because many other possible causes of
      hepatitis existed in this case. Not ruled out as potential causes of the clinical
      and laboratory adverse events were hepatitis other than hepatitis A or B. Other
      antimicrobials administered were dismissed. In particular, extended treatment
      with amoxicillin-clavulanate has been clearly linked to hepatotoxic effects that
      may occur long after therapy begins. Thus, while we agree that physicians must be
      aware of the potential for antimicrobial hepatotoxicity, we believe that this
      case study is not a solidly documented case of hepatitis attributable to
      gatifloxacin and overlooks other possible causes of acute hepatitis of which
      prescribers should be aware.

PMID- 12066974
TI  - Sodium oxybate (GHB) for treatment of cataplexy.

PMID- 12066975
TI  - Concomitant administration of drugs known to decrease the systemic availability
      of gatifloxacin.

PMID- 12066976
TI  - Modelling the role of humic acid in radiocaesium distribution in a British upland
      peat soil.
AB  - The significance of exchange sites on organic matter in the retention of
      radiocaesium in highly organic soils remains unclear. To quantify this retention,
      we measured the binding of 134Cs to a humic acid isolated from a British upland
      peat soil, under a range of chemical conditions. We interpreted our results using
      Humic Ion Binding Model V, a model of humic substance chemistry which simulates
      ion exchange by non-specific accumulation of cations adjacent to the humic
      molecules. Model V could simulate the humic acid-solution partitioning of Cs
      under all the solution conditions used. The model was used to estimate the
      contribution of organic matter to Cs sorption by the whole soil composite. An
      estimate of Cs sorption by illite frayed edge sites was also made. These
      simulations show that organic matter may play only a minor role in binding Cs.
      even in highly organic soils.

PMID- 12066977
TI  - Comparative studies of health hazard from radon (Rn-222) in two selected
      lithologic formations in the Suwalki region (in Poland).
AB  - The aim of this work was to make a comparison of indoor radon concentrations in
      dwellings and in soil air in the area of two geological formations in the Suwalki
      region (Poland). The mean arithmetic airborne concentration was found to be the
      highest (301 Bq m (-3)) in the basements of buildings in the gravel and sand
      areas, whereas in the boulder clay areas it reached 587 Bq m (-3). Out of 54
      measurements of radon concentrations performed at the ground floor, in eight
      cases concentrations were found to exceed 200 Bq m (-3) - permissible radon level
      in new-built houses in Poland and in three cases these values were even higher
      than 400 Bq m (-3). The highest radon levels were noted in houses with earthen
      basement floors and with direct entrance from the basement to rooms or kitchens.
      The mean arithmetic radon concentration in the soil air in the sandy and gravel
      formations was 39.7 kBq m (-3) and in clay formation it was 26.5 kBq m (-3).
      Higher radon levels were also found in the water obtained from household wells
      reaching 8367 Bq m (-3) as compared with tap water (2690 Bqm (-3)). The mean
      indoor concentration for the whole area under study was found to be 169.4 Bq m (
      3), which is higher than the mean value for Poland (49.1 Bq m (-3)) by a factor
      of 3.5.

PMID- 12066978
TI  - Abnormal high natural radium concentration in surface waters.
AB  - Unexpected high 228Ra concentrations, up to 2 Bq 1(-1), were found in waters of a
      coastal lagoon close to a monazite sand separation plant. Due to their use as
      process waters in this plant, the initial supposition was a contamination related
      to its operation. However, it was concluded that these abnormal radium
      concentrations had a natural origin, springs at the lagoon head area with high
      228Ra and 226Ra concentrations. The strong relationship among radium and light
      rare-earth elements (LREEs), the observed 228Ra/226Ra activity ratio and the rare
      earth element pattern in the spring waters suggested that monazite is the main
      source of nuclides for water, indicating the disturbance of monazite chemical
      stability by the combined effects of low pH and high salinity. Both factors
      combined allow relatively low mobility of thorium, but, on the other hand, a
      relatively high mobility of radium and LREEs.

PMID- 12066979
TI  - Application of multivariate statistical analyses in the interpretation of
      geochemical behaviour of uranium in phosphatic rocks in the Red Sea, Nile Valley
      and Western Desert, Egypt.
AB  - Factor and cluster analyses as well as the Pearson correlation coefficient have
      been applied to geochemical data obtained from phosphorite and phosphatic rocks
      of Duwi Formation exposed at the Red Sea coast. Nile Valley and Western Desert.
      Sixty-six samples from a total of 71 collected samples were analysed for SiO2,
      TiO2, Al203, Fe2O3, CaO, MgO, Na2O, K2O, P2O5, Sr, U and Pb by XRF and their
      mineral constituents were determined by the use of XRD techniques. In addition,
      the natural radioactivity of the phosphatic samples due to their uranium, thorium
      and potassium contents was measured by gamma-spectrometry. The uranium content in
      the phosphate rocks with P2O5 > 15% (average of 106.6 ppm) is higher than in
      rocks with P2O5 < 15% (average of 35.5 ppm). Uranium distribution is essentially
      controlled by the variations of P2O5 and CaO, whereas it is not related to
      changes in SiO2, TiO2, Al2O3, Fe2O3, MgO, Na2O and K2O concentrations.-Factor
      analysis and the Pearson correlation coefficient revealed that uranium belaves
      geochemically in different ways in the phosphatic sediments and phosphorites in
      the Red Sea, Nile Valley and Western Desert. In the Red Sea and Western Desert
      phosphorites, uranium occurs mainly in oxidized U6+ state where it seems to be
      fixed by the phosphate ion, forming secondary uranium phosphate minerals such as
      phosphuranylite. In the Nile Valley phosphorites, ionic substitution of Ca2+ by
      U4 is the main controlling factor in the concentration of uranium in phosphate
      rocks. Moreover, fixation of U6- by phosphate ion and adsorption of uranium on
      phosphate minerals play subordinate roles.

PMID- 12066980
TI  - Evaluation of technologically enhanced natural radiation near the coal-fired
      power plants in the Lodz region of Poland.
AB  - Radionuclide releases together with escaping fly ashes (from 45 x 10(6) kg in
      previous decades to 8 x 10(6) kg annually in 1996) from the main local and
      several small coal-fired power plants resulted in a relatively small increase in
      natural radioactivity levels in the Lodz region. The natural gamma terrestrial
      radiation dose rates (1 m above ground level) were measured at 82 points
      including in the vicinity of power plants, in the center of the town and on edge
      of the town. The average dose rate value for the first area was 36 +/- 1.2 nGy h
      (-1), whereas the same dose rate for the edge of town was slightly lower 30 +/-
      0.9 nGy h (-1) but this difference was statistically significant. Further
      confirmation of the technologically slightly enhanced exposure of the local
      population to natural radionuclides was achieved by gamma-spectrometry
      measurement of the uranium and thorium decay series radionuclides in the surface
      soil profiles (up to 30 cm depth). The average increase of 226Ra and 232Th
      radionuclides in the top layer of soil (0-10 cm) according to the 20+/-30 cm
      depth layer was 21% and 17%, respectively. However, due to the relatively low
      levels of 232Th (14.3 Bq kg (-1)) and 238U (16.8 Bq kg (-1)) in this area, the
      annual average effective dose from the natural terrestrial radiation for the
      local population is also relatively low, 0.28 mSv only.

PMID- 12066981
TI  - 137Cs and 210Po dose assessment from marine food in Cienfuegos Bay (Cuba).
AB  - One part of Radiological Monitoring Programme in central Cuba (1991-1995) was
      dedicated to study the background levels of natural and anthropogenic
      radioactivity in Cienfuegos Bay in the vicinity of the first Cuban nuclear power
      station under construction. 210Po and 137Cs concentrations in fish, molluscs and
      crustaceans collected in Cienfuegos Bay were determined and the committed
      effective doses (CED) were calculated for two population groups inhabiting this
      region. The highest values of 210Po concentrations were found in crustaceans, but
      significant accumulation was also observed in fish and molluscs. The mean 137Cs
      concentrations in organisms are several times lower with respect to 210Po, a
      situation that characterises the regions affected by the global fallout only.
      Values of CED from the consumption of crustaceans and molluscs are very low both
      from 210Po and 137Cs. The mean individual dose from 210Po in the seafood consumed
      varies from 39 microSv for general populations to 2802 microSv for the "critical
      group" consuming 320 kg of fish per year. The dose from 137Cs is negligible.

PMID- 12066982
TI  - The influence of the sorptive properties of organic soils on the migration rate
      of 137Cs.
AB  - Using a compartment model, the migration rates of 137Cs were calculated for two
      types of organic soils: a low peat-muck soil and a black earth. The migration
      rates of 137Cs in the tested soils turned out to be significantly higher than in
      mineral types examined earlier and ranged from 0.6 to 12.3 cm/year. The partition
      coefficients (Kd) were also determined for samples with varying organic matter
      content (OM) that were taken from different layers of the studied soils. The
      experimental results indicate that there is a clear relationship between Kd
      values and OM. The investigation was widened by microcalorimetric measurements
      which confirmed that the adsorption of 137Cs on the organic soils is low.

PMID- 12066983
TI  - Determination of uranium and radon in potable water samples.
AB  - In this work, potable water samples collected from boreholes of the Migdonia
      valley, located NE of the city of Thessaloniki, were analyzed for the
      determination of uranium (238U) and radon (222Rn) concentrations. The objective
      of the present work is to examine if there is any correlation between radon and
      uranium concentrations in the water samples. For the determination of traces of
      uranium in water samples, an analytical technique was developed based on the
      selective adsorption of uranium on the chelating resin, SRAFION NMRR, and the in
      situ determination of the retained uranium by instrumental neutron activation
      analysis (INAA). By the described procedure, it was possible to determine uranium
      amounts in the range of microg/l. For measuring radon in water, a liquid
      scintillation counting system, using the Packard protocol was employed. The
      measured 222Rn activity concentrations are from background level up to 160 Bq l (
      1).

PMID- 12066984
TI  - Radiosensitivity of subterranean bacteria in the Hungarian Upper Permian
      Siltstone Formation.
AB  - The main purpose of this work was to study the radioresistance of subterranean
      aerobic and anaerobic isolates from the Hungarian Upper Permian Siltstone
      (Aleurolite) Formation, in order to assess the safety of potential sites of
      future underground repositories for nuclear waste. A total of 93 isolates were
      studied. The radiosensitivities of these aerobic and anaerobic bacteria isolates
      were determined: the D10 values (decimal reducing doses) of the aerobic spore
      formers lay in the range 0.80 -2.44 kGy, and those of the anaerobic spore-formers
      lay in the range 1.86 4.93 kGy. The D10 values of the aerobic and anaerobic
      vegetative isolates were much lower, in the ranges 0.11 0.57 and 0.22-0.40 kGy.
      respectively. The variability in bacterial radioresistance indicates the
      biodiversity at this potential disposal site. These results can affect the
      construction of a future underground repository, since knowledge of the most
      resistant microorganism may be of importance as concerns calculation of the time
      required to inactivate the bacteria surrounding the containers.

PMID- 12066985
TI  - Sexual orientation identification of men who have sex with men in public settings
      in Canada.
AB  - The present study attempts to determine how men who have sex with men (MSM)
      identify in terms of their sexual orientation. The sexual identity of MSM has
      important implications for the spread of HIV. The literature suggests that gay or
      bisexual identifying MSM are more likely to practice safer sex than
      heterosexually-identified MSM. A significant number of the MSM in public
      settings, such as parks, are believed to be heterosexual identifying. MSM in
      bathhouses are presumed to be gay or bisexual identifying. Parks have been the
      focus of safer sex outreach efforts targeted towards heterosexually-identified
      MSM. Sexual orientation self-identification was ascertained from park and
      bathhouse users via one-on-one interactions with outreach workers from 1996 to
      1998. Chi-square analysis revealed no significant difference in the expressed
      sexual orientation of bath and park users, with both populations consisting
      mostly of gay-identified men. Heterosexually-identified MSM are not found in
      significant numbers in public settings. The current micro educational approach
      used to target these men may not be cost-effective. Alternative strategies are
      discussed.

PMID- 12066986
TI  - Sodomites and police in Paris, 1715.
AB  - The Archives of the Bastille in the Bibliotheque de l'Arsenal include hundreds of
      police reports, none of them currently available in English or even in print,
      about male same-sex relations in Paris during the first half of the eighteenth
      century. The documents translated here, interrogations of eight men arrested in
      1715, provide information about networks and prostitution, age and class,
      surveillance and deception in the sodomitical subculture of the capital.

PMID- 12066987
TI  - Fighting desires: Henry Miller's Queer Tropic.
AB  - "Fighting Desires: Henry Miller's Queer Tropic" is an investigation of Tropic of
      Cancer that investigates the deeply repressed homoerotic desire that periodically
      surfaces. This reading is dependent upon an interpretation of Eve Sedgwick that
      proposes male sexuality as a continuum. By looking at the nature of the male-male
      relationships, as well as the lack of emotion and presence in the male-female
      relationships, I will show that the most intimate relationships are between men,
      and that these relationships are expressed through the telling of stories about
      (heterosexual) sex; this is the function of women within the novel: one has sex
      with a woman, not for the pleasure that the act brings, but for the pleasure that
      the recounting of the story to other men brings. Furthermore, I will look at
      Miller's use of puns within the novel and how they also contribute to a
      homoerotic reading. None of this is to argue that Miller was not homophobic and
      sexist--Miller very clearly was--the purpose of this essay is to show the complex
      nature of sexuality, even within a protagonist who asserts a very defined
      heterosexuality.

PMID- 12066988
TI  - A brief history of the E-Directory of lesbigay scholars.

PMID- 12066989
TI  - Greetings from the Schochet Center for GLBT studies! The reincarnation of
      "Louie's List".

PMID- 12066990
TI  - Size matters: a comparison of anti- and pro-gay organizations' estimates of the
      size of the gay population.
AB  - This articles examines estimates of the size of the gay population that are
      provided in the Websites of pro- and anti-gay groups. There are marked
      differences in the estimates that are provided by these groups. While most pro
      gay groups suggest that approximately ten percent of the population is gay, anti
      gay groups argue that only 1-3 percent of the population is gay. While none of
      the pro-gay groups address the methodological problems associated with the Kinsey
      data, all of the anti-gay groups that address the issue of size discredit
      Kinsey's work and/or the ten percent estimate that comes from Kinsey's work and
      is often cited by pro-gay organizations.

PMID- 12066991
TI  - Men who have sex with men and also inject drugs-profiles of risk related to the
      synergy of sex and drug injection behaviors.
AB  - OBJECTIVES: Men who have sex with men and also inject drugs (MSM-IDU) are among
      the groups at highest risk for acquiring and transmitting HIV in Colorado and the
      US. We conducted formative research and a survey among MSM-IDU in Denver to
      better understand sexual and drug HIV risk behaviors and how they interact.
      METHODS: Formative data were collected with 30 persons who work, live or
      otherwise interact with MSM-IDU using a semi-structured interview instrument.
      Survey data on sexual and drug risk behaviors were collected with 100 MSM-IDU;
      eligible participants have had sex with men and injected drugs within the past
      six months. RESULTS: Results from formative research were used to generate the
      survey instrument. The survey results demonstrate high-risk sexual behaviors with
      multiple partners of both genders; 82% of the sample had primary and non-primary
      male partners, 20% had non-primary female partners, and 15% exchanged money or
      drugs for sex. Condom use was inconsistent and infrequent for all types of sex
      (vaginal, anal and oral) and with all types of partners. Drug risk behaviors
      highlight that the injection drugs of choice for this sample (90% shoot cocaine
      and 59% shoot methamphetamine) stimulate sexual desire and cocaine injection
      increases opportunities for injection risk behavior. Forty-five percent of the
      sample were HIV-infected. Significant differences between HIV infected and non
      infected men were not observed with regard to many sexual and drug risk
      behaviors. CONCLUSIONS: These data show that MSM-IDU are engaging in multiple
      risk behaviors that may have a synergistic effect on HIV transmission, and that
      their injection drug of choice contributes to their risk. That there do not
      appear to be consistent differences in preventive behaviors between men with or
      without HIV infection suggests a greatly increased risk for HIV transmission in
      this group of men and their partners. Because MSM-IDU do not identify strongly
      with either MSM because they may not gay identify or IDU because they do not use
      heroin, targeted HIV prevention strategies for this group are urgently needed.

PMID- 12066992
TI  - The relationship between sexism and attitudes toward homosexuality in a sample of
      Turkish college students.
AB  - This study examined the relationship of sexism, having traditional and
      conservative values, and contact with homosexual individuals to attitudes toward
      homosexuality. Two hundred seven male and female students from Middle East
      Technical University completed Hudson and Rickett's Homophobia scale, Glick and
      Fiske's Ambivalent Sexism Inventory and questions about: (1) their sexual
      preferences, (2) whether they described themselves as traditional and
      conservative, and (3) whether they knew a homosexual or not. Sexist attitudes,
      being more traditional and conservative, and not knowing any homosexual
      individuals all predicted more negative attitudes toward homosexuality. The
      correlation between hostile sexism and anti-homosexual attitudes was higher than
      the correlation between benevolent sexism and anti-homosexual attitudes. In
      addition, male, as compared to female, respondents were both more sexist and held
      more negative attitudes toward homosexuality.

PMID- 12066993
TI  - Effects of the gay publishing boom on classes of titles retrieved under the
      subject headings "Homosexuality," "Gay Men," and "Gays" in the OCLC WorldCat
      database.
AB  - What do searchers find when they look for literature on homosexuality? This
      question has profound implications for older as well as younger gays in their
      coming out, as well as in their subsequent identity development. Library records
      provide credible data to answer the question, since they represent relatively
      free sources of information, unlike data from bookstores, publishers, and some
      World Wide Web sites. The records of WorldCat, the world's largest union database
      of library records, comprise over 30 million records listed in the Online
      Computer Library Center. For the purposes of the study, 18,757 records listed
      under "Homosexuality," "Gay Men," and "Gays" were downloaded; records for
      "Lesbian" and "Lesbians" were not examined. Findings of the study suggest that
      while there has indeed been considerable growth in terms of the quantity of gay
      literature produced since 1969, such gains may be offset by the deteriorating
      quality of cataloging copy, which makes the experience of browsing records a
      discouraging and confusing one.

PMID- 12066994
TI  - Lost in translation? The hazards of applying social constructionism to
      quantitative research on sexual orientation development.
AB  - This article explores the hazards faced by social constructionists who attempt to
      conduct quantitative research on sexual orientation development. By critically
      reviewing two quantitative research studies, this article explores the ways in
      which the very nature of social constructionist arguments may be incongruous with
      the methodological requirements of quantitative studies. I suggest this conflict
      is a result of the differing natures of these two modes of scholarly inquiry.
      While research requires the acceptance of certain analytical categories, the
      strength of social constructionism comes from its reflexive scrutiny and
      problematization of those very categories. Ultimately, social constructionists
      who try to apply their theories/perspectives must necessarily conform to the
      methodological constraints of quantitative research. The intent of this article
      is not to suggest that it is futile or self-contradictory for social
      constructionists to attempt empirical research, but that these are two distinct
      modes of scholarly inquiry which can, and should, co-exist in a dialectical
      relationship to each other.

PMID- 12066995
TI  - Ultrasound-guided nerve blocks.

PMID- 12066996
TI  - Effects of anaesthetic agents on airway smooth muscles.

PMID- 12066997
TI  - Implanted cardiac pacemakers and defibrillators in anaesthetic practice.

PMID- 12066998
TI  - Ultrasonographic assessment of topographic anatomy in volunteers suggests a
      modification of the infraclavicular vertical brachial plexus block.
AB  - BACKGROUND: The infraclavicular vertical brachial plexus block, first described
      by Kilka and coworkers, offers a more proximal spread of anaesthesia for the
      upper extremity than the classic axillary approach. In this technique, the
      puncture site is defined as lying at the exact centre of an infraclavicular line
      (k) between the jugular fossa and the ventral process of the acromion. Our study
      was designed to determine whether the point so defined (P) corresponds with the
      optimal puncture site determined sonographically (S) and to develop an improved
      prediction model. METHOD: High-resolution ultrasonography was carried out in 59
      volunteers to visualize the plexus. Sonography-derived distances and morphometric
      measurements were used to test accuracy and calculate multiple regressions.
      RESULTS: We found a clear trend towards a more lateral puncture site. In women, S
      was significantly (P<0.001) lateral (8 mm) to P. The overall accuracy of the
      infraclavicular vertical brachial plexus block technique was not sufficient to
      predict the optimal puncture site reliably. Our resulting improved prediction
      model is valid for both sexes and is based not just on the centre point but on
      the absolute length of k (22-22.5 cm). We found that for every 1 cm decrease in k
      the optimal puncture site moved 2 mm laterally from the exact centre of k, and
      for every 1 cm increase in k it moved 2 mm medially. CONCLUSIONS: The suggested
      modification should help to increase the success rate of the infraclavicular
      vertical brachial plexus block while decreasing the rate of potentially severe
      complications, although individual ultrasonographic guidance is to be recommended
      whenever possible.

PMID- 12067000
TI  - EEG signal processing in anaesthesia. Use of a neural network technique for
      monitoring depth of anaesthesia.
AB  - BACKGROUND: The Bispectral Index (BIS) is a proprietary index of anaesthesia
      depth, which is correlated with the level of consciousness and probability of
      intraoperative recall. The present study investigates the use of a neural network
      technique to obtain a non-proprietary index of the depth of anaesthesia from the
      processed EEG data. METHODS: Two hundred patients, who underwent general
      abdominal surgery, were recruited for our trial. For anaesthesia we used a total
      i.v. technique, tracheal intubation, and artificial ventilation. Fourteen EEG
      variables, including the BIS, were extracted from the EEG, monitored with an EEG
      computerized monitor, and then stored on a computer. Data from 150 patients were
      used to train the neural network. All the variables, excluding the BIS, were used
      as input data in the neural network. The output targets of the network were
      provided by anaesthesia scores ranging from 10 to 100 assigned by the
      anaesthesiologist according to the observer's assessment of alertness and
      sedation (OAA/S) and other clinical means of assessing depth of anaesthesia. Data
      from the other 50 patients were used to test the model and for statistical
      analysis. RESULTS: The artificial neural network was successfully trained to
      predict an anaesthesia depth index, the NED (neural network evaluated depth),
      ranging from 0 to 100. The correlation coefficient between the NED and the BIS
      over the test set was 0.94 (P<0.0001). CONCLUSION: We have developed a neural
      network model, which evaluates 13 processed EEG parameters to produce an index of
      anaesthesia depth, which correlates very well with the BIS during total i.v.
      anaesthesia with propofol.

PMID- 12066999
TI  - Non-invasive assessment of cardiovascular autonomic activity induced by brief
      exposure to 50% nitrous oxide in children.
AB  - BACKGROUND: The use of the equimolecular mixture of oxygen and nitrous oxide is
      widely recommended for relief of pain in children undergoing minor procedures.
      Although the benefits and adverse effects of the clinical use of nitrous oxide
      seem well known, its effects on the autonomic nervous system have never been
      studied in children. The aim of this study was to evaluate changes in autonomic
      cardiovascular activity induced by brief exposure to 50% nitrous oxide in
      children. This study was based on non-invasive continuous recordings of RR
      interval and non-invasive arterial pressure. Vascular and cardiac sympathetic
      activity and cardiac parasympathetic activity were investigated using spectral
      analysis of systolic arterial pressure variability (SAPV) and RR-interval
      variability (RRIV). In addition, the sensitivity of the spontaneous baroreflex
      (SBR) was assessed using the sequences and the cross-spectral analysis methods.
      METHODS: Sixteen non-pre-medicated pre-pubertal children undergoing middle-ear
      surgery, were studied. Data analysis was performed at three points: baseline,
      when the end-tidal concentration of nitrous oxide was stabilized at 50%, and
      after withdrawing nitrous oxide. Low (0.04-0.14 Hz) and high frequency (0.2-0.6
      Hz) components of the spectral power of RRIV and SAPV, and SBR sensitivity were
      calculated using these 2-min data epochs. RESULTS: Our results show that brief
      exposure to 50% nitrous oxide in children results in: (1) absence of effect on
      mean AP and SAPV; (2) attenuation of the low frequency component of heart rate
      variability with a shift of the sympathetic-parasympathetic cardiac balance
      toward a parasympathetic predominance; and (3) absence of alteration of
      spontaneous baroreflex sensibility. CONCLUSIONS: Unlike the results demonstrated
      in adults, our findings show very few cardiovascular effects of nitrous oxide in
      children. Furthermore, whereas in adults nitrous oxide is associated with an
      excitatory cardiovascular profile, in children this agent seems to be associated
      with a depressant cardiovascular profile. The rapid return to baseline after
      discontinuation of administration and the absence of baroreflex changes are
      positive attributes for the use of nitrous oxide in children.

PMID- 12067001
TI  - Respiratory response to skin incision during anaesthesia with infusions of
      propofol and alfentanil.
AB  - BACKGROUND: The ventilatory response to skin incision during anaesthesia with
      enflurane is an increase in tidal volume without a change in frequency. As
      opioids affect respiratory frequency and also affect the processing of pain, we
      investigated if the breathing response to a painful stimulus could be different
      during anaesthesia using opioids. METHODS: We studied 12 patients during
      anaesthesia with target-controlled infusions of propofol (plasma target
      concentration 4-6 microg ml(-1)) and alfentanil (plasma target concentration 40
      60 ng ml(-1)), having varicose vein surgery. RESULTS: After the initial skin
      incision, tidal volume increased promptly by 17 (4, 81)% (median, quartile
      values) (P<0.01). Respiratory frequency changed variably with no significant
      change overall [median change 2 (-8, +50)%]. The duration of inspiration was
      virtually unaltered, and the duration of expiration decreased gradually by 5 (-7,
      32)%. Patients who showed more response also showed more change in tidal volume,
      so that there was a significant relationship between increased inspiratory flow
      rate and reduced expiratory time (P<0.05). CONCLUSIONS: During opioid
      anaesthesia, the mechanism of ventilatory increase after stimulation involves
      changes in both drive and timing of breathing. This pattern of response does not
      resemble the changes seen during anaesthesia with potent volatile agents.

PMID- 12067002
TI  - Propofol metabolites in man following propofol induction and maintenance.
AB  - BACKGROUND: The pharmacokinetics of propofol in man is characterized by a rapid
      metabolic clearance linked to glucuronidation of the parent drug to form the
      propofol-glucuronide (PG) and sulfo- and glucuro-conjugation of hydroxylated
      metabolite via cytochrome P450 to produce three other conjugates. The purpose of
      this study was to assess the urine metabolite profile of propofol following i.v.
      propofol anaesthesia in a Caucasian population. METHODS: The extent of phase I
      and phase II metabolism of propofol was studied in 18 female and 17 male patients
      after an anaesthesia induced and maintained for at least 4 h with propofol. The
      infusion rates (mg kg(-1) h(-1)) of propofol were (mean (SD)) 4.1 (1.0) and 4.5
      (1.3) for males and females, respectively. Urine was collected from each patient
      for the periods 0-4, 4-8, 8-12, and 12-24 h after the start of propofol
      administration. In a preliminary study, the three main glucuro-conjugated
      metabolites were isolated from urine and characterized by magnetic resonance
      spectroscopy. The quantification of these metabolites for the different
      collection periods was then performed by a HPLC-UV assay. RESULTS: Total recovery
      of propofol in the metabolites studied amounts to 38%, of which 62% was via the
      PG metabolite and 38% via cytochrome P-450. This percentage is significantly
      higher than that previously reported from patients after a bolus dose of
      propofol. Extreme values for PG (0-24 h period) were included from 73 to 49%.
      There was no significant difference between female and male patients in the
      metabolite ratio. CONCLUSIONS: We conclude that the extent of hydroxylation in
      propofol metabolism was higher than in previous findings after administration of
      anaesthetic doses of propofol. Moreover, the ratio between hydroxylation and
      glucuronidation of propofol is subject to an inter-patient variability but this
      does not correlate with the dose of propofol. However, the variation of the
      metabolite profile observed in the present report does not seem to indicate an
      extended role of metabolism in pharmacokinetic variability.

PMID- 12067003
TI  - Volatile anaesthetics may be the main cause of early but not delayed
      postoperative vomiting: a randomized controlled trial of factorial design.
AB  - BACKGROUND: Despite intensive research, the main causes of postoperative nausea
      and vomiting (PONV) remain unclear. We sought to quantify the relative importance
      of operative, anaesthetic and patient-specific risk factors to the development of
      PONV. METHODS: We conducted a randomized controlled trial of 1180 children and
      adults at high risk for PONV scheduled for elective surgery. Using a five-way
      factorial design, we randomly assigned subjects by gender who were undergoing
      specific operative procedures, to receive various combinations of anaesthetics,
      opioids, and prophylactic antiemetics. RESULTS: Of the 1180 patients, 355 (30.1%
      95% CI (27.5-32.7%)) had at least one episode of postoperative vomiting (PV)
      within 24 h post-anaesthesia. In the early postoperative period (0-2 h), the
      leading risk factor for vomiting was the use of volatile anaesthetics, with
      similar odds ratios (OR (95% CI)) being found for isoflurane (19.8 (7.7-51.2)),
      enflurane (16.1 (6.2-41.8)) and sevoflurane (14.5 (5.6-37.4)). A dose-response
      relationship was present for the use of volatile anaesthetics. In contrast, no
      dose response existed for propofol anaesthesia. In the delayed postoperative
      period (2-24 h), the main predictors were being a child (5.7 (3.0-10.9)), PONV in
      the early period (3.4 (2.4-4.7)) and the use of postoperative opioids (2.5 (1.7
      3.7)). The influence of the antiemetics was considerably smaller and did not
      interact with anaesthetic or surgical variables. CONCLUSION: Volatile
      anaesthetics were the leading cause of early postoperative vomiting. The pro
      emetic effect was larger than other risk factors. In patients at high risk for
      PONV, it would therefore make better sense to avoid inhalational anaesthesia
      rather than simply to add an antiemetic, which may still be needed to prevent or
      treat delayed vomiting.

PMID- 12067004
TI  - Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative
      patients requiring intensive caret.
AB  - BACKGROUND: The pharmacokinetics of the alpha-2 adrenoceptor agonist
      dexmedetomidine were studied in 10 patients requiring postoperative sedation and
      mechanical ventilation in the intensive care unit (ICU), and compared with
      previous volunteer data. METHODS: On arrival in the ICU, sedation with
      dexmedetomidine was commenced with a loading dose of 2.5 microg kg(-1) h(-1) over
      10 min followed by a maintenance infusion of 0.7 microg kg(-1) h(-1) into a
      central vein. Blood samples for measurement of plasma dexmedetomidine
      concentrations were taken during and after sedative infusions at predetermined
      intervals. Pharmacokinetic variables were estimated using non-compartmental
      methods. In addition, non-linear mixed effects modelling was used to obtain
      variable estimates not readily attainable from non-compartmental methods.
      Respiratory and haemodynamic data were recorded to enable correlation of any
      adverse events with the calculated pharmacokinetic profile. RESULTS: The harmonic
      mean distribution half-life of dexmedetomidine was 8.6 min and the harmonic mean
      terminal half-life was 3.14 h. Steady-state volume of distribution averaged 173
      litres, clearance averaged 48.3 litres h(-1), and the mean residence time
      averaged 3.86 h. CONCLUSIONS: Mean dexmedetomidine pharmacokinetic variables seen
      in postoperative, intensive care patients were similar to those previously found
      in volunteers, with the exception of the steady-state volume of distribution. A
      small loading dose provided effective sedation with no adverse events.

PMID- 12067005
TI  - Comparison of articaine and bupivacaine/lidocaine for peribulbar anaesthesia by
      inferotemporal injection.
AB  - BACKGROUND: Articaine is a novel amide local anaesthetic with a shorter duration
      of action than prilocaine. METHODS: In a randomized, double-blind study we
      compared the efficacy of 2% articaine with epinephrine 1:200,000 with a mixture
      of 0.5% bupivacaine and 2% lidocaine with epinephrine 1:200,000 for peribulbar
      anaesthesia in cataract surgery using a single inferotemporal injection. Eighty
      two patients were randomly allocated to one of two groups to receive peribulbar
      anaesthesia with 6-7 ml of articaine or a bupivacaine/lidocaine mixture. Both
      solutions contained hyaluronidase 30 iu ml(-1). Ocular movement was scored at 2
      min intervals up to 10 min, at the end of surgery and at time of discharge from
      hospital. Time to readiness for surgery and any complications (proptosis,
      chemosis, pain) were recorded. RESULTS: The articaine group demonstrated a rapid
      onset of peribulbar block with mean time (SD) to readiness for surgery of 4.2
      (4.5) min compared with 7.2 (5.7) min in the bupivacaine/lidocaine group
      (P=0.0095). The block obtained in the articaine group was dense with eye movement
      scores at 2, 4, 6, 8 and 10 min all significantly reduced (P<0.01 at each
      interval). There was also a faster offset of the block in the articaine group
      (P=0.0009). There was no difference in incidence of minor complications between
      the groups. CONCLUSIONS: Two per cent articaine is safe and effective for
      peribulbar anaesthesia by inferotemporal injection and is a suitable alternative
      to the traditional mixture of 0.5% bupivacaine and 2% lidocaine.

PMID- 12067006
TI  - Antinociceptive role of 5-HT1A receptors in rat spinal cord.
AB  - BACKGROUND: Intrathecal administration of 5-hydroxytryptamine (5-HT) is
      antinociceptive to noxious heat and electrical stimuli. The contributions of
      different receptor subtypes to the antinociceptive effects of 5-HT are
      controversial. The main reasons for this are the poor receptor subtype
      selectivity of some agonist drugs and the difficulty of restricting drug action
      to the spinal cord in some experimental paradigms. This study investigated the
      roles of different 5-HT receptor subtypes involved in the spinal cord control of
      the nociception produced by these two nociceptive testing paradigms. METHODS:
      Tail-flick latency and electric current threshold for nociception were measured
      in an acute pain model that allowed the study of the antinociceptive effects of
      intrathecally administered drugs that were due to actions of these drugs at
      spinal cord receptors. Experiments were performed in male Wistar rats with
      chronically implanted lumbar subarachnoid catheters. Dose-response curves for
      spinally mediated antinociceptive effects of agonists selective for 5-HT receptor
      subtypes were constructed. RESULTS: The 5-HT1 agonist 1-(3-chlorophenyl)
      piperazine dihydrochloride caused a dose-dependent antinociceptive effect,
      measured by both nociceptive tests. However, 8-hydroxy-DPAT (selective 5-HT1A
      agonist) produced antinociception assessed by electric current but not tail
      flick. A 5-HT1A-selective antagonist, 4-[3-(benzotriazol-1-yl)propyl]-1-(2
      methoxyphenyl)-piperazine, reversed the antinociception in the electrical test
      produced by both of these agonists but the tail-flick latency effects after
      intrathecal 1-(3-chlorophenyl)-piperazine were not suppressed by this antagonist.
      CONCLUSIONS: We conclude that 5-HT1A receptors in the spinal cord are involved in
      the nociceptive mechanisms assessed by noxious electrical stimuli. Other 5-HT1
      receptors (non 5-HT1A receptors) are involved in the spinally mediated
      antinociception assessed by thermal noxious stimuli.

PMID- 12067007
TI  - Potentiation by ketamine of fentanyl antinociception. I. An experimental study in
      rats showing that ketamine administered by non-spinal routes targets spinal cord
      antinociceptive systems.
AB  - BACKGROUND: Ketamine has been found to exert antinociceptive effects in animals
      and to be analgesic at subanaesthetic doses in humans. This study was designed to
      investigate the involvement of spinal cord mechanisms in the potentiation of
      opioid analgesia by parenteral non-spinal administration of ketamine. METHODS:
      Thresholds for nociception were measured in an acute pain model in rats that
      allowed identification of antinociceptive effects due to drug action in the
      spinal cord. Dose-response curves for the antinociceptive effects of ketamine
      alone and ketamine in conjunction with the mu opioid fentanyl were constructed.
      RESULTS: Intraperitoneal ketamine up to 3.75 mg kg(-1) caused no sedative or
      antinociceptive effects and intrathecal ketamine caused dose-dependent, spinally
      mediated antinociceptive effects. Injections of ketamine doses that caused no
      antinociceptive effects when given alone (intrathecal 25 microg and
      intraperitoneal 3.75 mg/kg) significantly increased spinally mediated
      antinociception produced by intrathecal fentanyl injections when assessed using
      noxious heat (tail-flick test) but not when assessed by noxious electrical
      current (electrical current threshold test). CONCLUSIONS: We conclude that
      ketamine can potentiate the effects of fentanyl by an interaction at the level of
      the spinal cord even when ketamine is given via a non-spinal route of
      administration.

PMID- 12067008
TI  - Molecular conformation-activity relationship of decamethonium congeners.
AB  - BACKGROUND: Of the polymethylene bismethonium congeners (C5-C12 and C18),
      decamethonium (C10) is the most potent neuromuscular blocking agent. We tested
      the hypothesis that these congeners act as straight molecules and will not bend
      easily in spite of the flexible connecting chain between the methonium heads. For
      congeners higher than C10, we also hypothesized that the relative difficulty with
      which the molecules to bend to conform to the interonium distance of C10
      proportionately reduces their neuromuscular blocking potency. METHODS: Each
      congener was modelled and subjected to computer searches for representative low
      energy molecular conformers. The conformation-potency relationship of the
      congeners was examined. RESULTS: For all congeners, we found that the lowest
      energy conformer (the 'global minimum') has a straight-chain conformation.
      Reduction of the interonium distance (by bending) incurs a steep energy penalty
      linearly related to the distance reduced. The global minimum of C10 has an
      interonium distance of 14.03 A and a total molecular length of 20.10 A. For other
      congeners, the interonium distance differential from that of C10 and the energy
      penalty required to conform to the interonium distance of C10 (where applicable)
      correlate with the reported logarithmic (mmol kg(-1)) dose requirement for
      neuromuscular block. CONCLUSIONS: The C10 congeners strongly prefer a straight
      conformation. Their molecular length and resistance to bending is key to their
      neuromuscular blocking potency. A molecular length of approximately 20 A should
      best fit the space available to neuromuscular blocking agents between the two
      receptive sites of the endplate acetylcholine receptor.

PMID- 12067009
TI  - Heat stroke: implications for critical care and anaesthesia.

PMID- 12067010
TI  - High-frequency oscillation in adolescents.
AB  - BACKGROUND: High-frequency oscillation (HFO) is a widely used lung-protective
      ventilatory strategy in paediatric and neonatal acute lung injury. Its safe and
      effective use has been hindered by inadequate recruitment of the lung during
      oscillation and, until recently, the lack of an adequately powered oscillator for
      use in adult practice. METHODS: We present data from three adolescents with
      severe acute respiratory distress syndrome (ARDS) who received HFO with the
      Sensormedics 3100B oscillator after failure of conventional mechanical
      ventilation. A manual recruitment manoeuvre was used in all patients prior to
      mechanical ventilation (conventional or HFO) and following tracheal suctioning or
      disconnection from the ventilator. Changes in oxygenation index were used to
      assess therapy. RESULTS: All patients showed at least a 25% reduction in
      oxygenation index within 2 h of HFO, with return to conventional ventilation
      after 27-65 h. CONCLUSIONS: We found HFO, in conjunction with manual recruitment
      and prone positioning, to be a well-tolerated mode of ventilation in adolescents
      with ARDS and who were unresponsive to conventional ventilation. Given this
      success we hope to renew interest in this method for adults with ARDS, together
      with concurrent use of manual recruitment.

PMID- 12067011
TI  - The output of two sevoflurane vaporizers in the presence of helium.
AB  - BACKGROUND: Modern vaporizers are designed to deliver accurate and stable
      concentrations of volatile anaesthetic agents. Carrier gas composition may
      adversely affect the output from vaporizers. No previous study has tested helium
      in combination with sevoflurane vaporizers, a clinically useful combination
      especially in anaesthesia for upper airway obstruction. METHODS: This study
      evaluated the effect of increasing helium concentrations, carrier gas flow rates
      and varying the vaporizer dial setting on the output from Blease Datum and Drager
      Vapor 19.3 sevoflurane vaporizers. RESULTS: The presence of helium in the carrier
      gas had negligible effects on the output from both of the sevoflurane vaporizers
      tested. Carrier gas flow rates had the greatest effect on output but changes were
      within +/- 10% of baseline. CONCLUSION: Helium/oxygen mixtures can be used with
      these vaporizers without adversely affecting their performance.

PMID- 12067012
TI  - Does the opioid-sparing effect of rectal diclofenac following total abdominal
      hysterectomy benefit the patient?
AB  - BACKGROUND: The aim of this prospective, double-blind, randomized, placebo
      controlled clinical trial was to investigate the opioid-sparing effects of rectal
      diclofenac following total abdominal hysterectomy. METHODS: Forty ASA I-II
      patients, aged 20-60 yr, were randomized to receive identical-looking
      suppositories of either diclofenac 75 mg or placebo, twice daily. All patients
      were given a standardized anaesthetic, with intravenous morphine via a patient
      controlled analgesia device and either diclofenac or placebo for postoperative
      analgesia. RESULTS: The median 24 h morphine consumption (interquartile range)
      was significantly higher (P=0.02) in the placebo group [59 (45-85) mg] than in
      the diclofenac group [31 (14-65) mg]. In comparison with the placebo group, there
      were significant reductions in total pain score in the diclofenac group at rest
      (P=0.04) and on movement (P<0.01). Total (SD) sedation score was significantly
      lower (P=0.04) in the diclofenac group [90 (73) mm] than in the placebo group
      [148 (89) mm]. Total (interquartile range) nausea score was significantly lower
      (P<0.01) in the diclofenac group [14 (0-53) mm] than in the placebo group [64 (30
      109) mm]. There was no significant difference between the two groups of patients
      in episodes of vomiting or number of rescue antiemetics. CONCLUSIONS: Rectal
      diclofenac reduces morphine consumption, improves postoperative analgesia, and
      reduces the incidence of adverse effects such as sedation and nausea.

PMID- 12067013
TI  - Left ventricular preload and function during graded haemorrhage and retranfusion
      in pigs: analysis of arterial pressure waveform and correlation with
      echocardiography.
AB  - BACKGROUND: Arterial pressure waveform analysis is a new method for assessment of
      cardiac preload. Despite the close correlation of parameters derived by its use
      with the degree of blood loss, their relationship with more precise estimates of
      cardiac preload remains controversial. METHODS: Systolic pressure variation
      (SPV), delta up (dUp), and delta down (dDown), which are the changes in the
      arterial blood pressure (BP) during mechanical ventilation, were measured during
      graded haemorrhage and retransfusion in seven pigs under light halothane
      anaesthesia, and compared with changes in cardiac filling pressures and left
      ventricular end-diastolic volume (LVEDV), measured by echocardiography. RESULTS:
      Significant changes in preload parameters and stroke volume (SV) but not in BP
      and heart rate occurred. SPV, dDown, and cardiac filling pressures correlated
      significantly with LVEDV. Following retransfusion, LVEDV returned to baseline
      values but the SV and left ventricular ejection fraction were significantly low.
      This deterioration in myocardial performance was associated with elevated dUp.
      CONCLUSIONS: During mechanical ventilation, dDown and the SPV may serve as
      minimally invasive indicators of preload. The retransfusion stage that follows
      significant blood loss may be associated with deterioration in LV function.

PMID- 12067014
TI  - Neurological outcome prediction in a cardiorespiratory arrest survivor.
AB  - Outcome prediction of neurological recovery in an unconscious survivor of
      cardiorespiratory arrest is difficult and uncertain. We describe the case of a 25
      yr-old post-arrest survivor who made a remarkable neurological improvement
      despite a seemingly hopeless prognosis. Conventional clinical and
      neurophysiological assessments need to be interpreted with care in the presence
      of uncontrolled seizure activity and sedative medications. The measurement of
      biochemical markers in the serum and cerebrospinal fluid may be useful in helping
      the clinician to arrive at a more accurate neurological outcome prediction.

PMID- 12067015
TI  - Management of massive air leak following intubation injury in a very low birth
      weight infant.
AB  - Perforation of an infant's trachea after orotracheal intubation for general
      anaesthesia is a rarely described serious complication. This article reports an
      unusual case of laceration of the trachea in an 8-week-old infant with a history
      of prolonged neonatal intubation needed to treat hyaline membrane disease. After
      diagnosis the tracheal injury was managed conservatively. Factors involved in the
      occurrence of the injury and its management are discussed.

PMID- 12067016
TI  - Tracheostomy, lingular tonsillectomy and sleep-related breathing disorders.
AB  - Laser resection of lingual tonsils and formal closure of a tracheostomy improved
      the airway in a 14-yr-old patient with Down's syndrome. Non-invasive airway
      support to treat obstructive sleep apnoea was postponed with this treatment.
      During the anaesthetic a laryngeal mask airway was used to support the airway
      after lingual tonsillectomy, to assess the suitability of defunctioning the
      tracheostomy. Laryngeal mask airways assist management of lingual tonsils.
      Lingual tonsillar hypertrophy can lead to obstructive sleep disorders.

PMID- 12067018
TI  - Rigid nasendoscope with video camera system for intubation in infants with Pierre
      Robin sequence.
AB  - We describe an alternative intubation technique using a rigid nasendoscope and a
      video camera monitor system in two infants with Pierre-Robin sequence presenting
      for palatoplasty. After induction with an inhalational anaesthetic technique, the
      tracheas of the infants could not be intubated with direct laryngoscopy using a
      Wisconsin blade. In the absence of a flexible paediatric fibrescope, a rigid
      endoscope (2.7 mm, 70 degrees lateral illumination) was passed orally to provide
      a view of the glottis on the monitor screen. A tracheal tube, bent into a J-shape
      using a stylet, was inserted orally and manipulated into the trachea, under video
      guidance. This technique proved to be simple, permitting a favourable view of the
      glottis. It should be considered for passing a tracheal tube through the vocal
      cords in infants who present with a difficult airway.

PMID- 12067017
TI  - Airway management in an infant with congenital centrofacial dysgenesia.
AB  - The use of a laryngeal mask airway (LMA) on two occasions, in a 53-day-old and
      270-day-old male infant with Tessier N.3 and N.4 facial defects, using sedation
      and topical anaesthesia is described. The LMA was used to manage the airway and
      facilitate inhalation induction of anaesthesia as the facial deformities were
      thought to be too extensive for the safe use of a facemask. The LMA is an
      alternative to a facemask and secures the airway and facilitates the inhalation
      induction of anaesthesia in paediatric patients with severe facial deformities.

PMID- 12067019
TI  - Unsuspected concentric tracheal rings in a 14-year-old with scoliosis.
AB  - A 14-yr-old boy was first found to have tracheal stenosis when anaesthesia was
      induced for extensive scoliosis surgery in the prone position. There are no
      guidelines for airway management under these conditions. We describe how we
      managed the problem and suggest some useful modifications.

PMID- 12067020
TI  - Peripartum management of a patient with Glanzmann's thrombasthenia using
      Thrombelastograph.
AB  - We describe the perioperative management of a 31-yr-old primipara with
      Glanzmann's thrombasthenia, who required urgent Caesarean delivery at 33 weeks'
      gestation. Peripartum haemorrhage was inevitable and was pre-empted by
      transfusion of multiple blood products, the effects of which were monitored by
      Thrombelastograph. The blood products given are discussed.

PMID- 12067022
TI  - Severe anuric renal failure in a patient with tetanus.

PMID- 12067021
TI  - The importance of looking at the EEG when presenting univariate variables to
      describe it.

PMID- 12067023
TI  - Duration of hospital stay and perioperative morbidity in patients with hip
      fractures.

PMID- 12067024
TI  - In defence of paravertebral blockade.

PMID- 12067025
TI  - In defence of paravertebral blockade.

PMID- 12067026
TI  - Large dose acetaminophen reconsidered.

PMID- 12067027
TI  - 'Tears at bedtime' and how to avoid them.

PMID- 12067028
TI  - Epidural haematoma in a parturient with neurofibromatosis.

PMID- 12067029
TI  - Economic growth, inequality, and the economic position of the poor in 1985-1995:
      an international perspective.
AB  - The "trickle-down" theory argues that wider income differences are good for
      economic growth, that growth is good for the poor, and therefore that widening
      income disparities benefit the poor. The theory thus fulfills Rawlsian principles
      of justice. The purpose of this article is to present a preliminary evaluation of
      the correctness of this theory. Income data for 21 countries were obtained from
      the Luxembourg Income Study, for the period 1985-95. The results of the analysis
      show no clear connections between inequality and economic prosperity. The wider
      the inequality, the worse is the absolute income of the poor. In this respect the
      theory is falsified. However, the trickle-down theory is partly correct in
      arguing for the beneficial effects of economic growth for the poor: the absolute
      income level of the poor is dependent on what is happening in the national
      economy, while the incidence and depth of poverty in advanced countries are not
      so much associated with economic factors as a result of national social policy
      programs.

PMID- 12067030
TI  - The scorecard on globalization 1980-2000: its consequences for economic and
      social well-being.
AB  - The era of globalization has brought substantially less progress than was
      achieved in the preceding 20 years. This study by the Center for Economic and
      Policy Research concludes that the data provide no evidence that the policies
      associated with globalization have improved outcomes for developing countries,
      and its findings challenge economists and policymakers who cite globalization as
      an engine of growth while pressing for policies that strengthen the trend. The
      study also served as a backdrop to the release of the United Nations Development
      Program's Human Development Report on July 11, 2001. Using standard measures of
      economic growth, health outcomes, education, and literacy, the CEPR study
      compares the progress achieved during the period preceding globalization, 1960
      80, with the period from 1980 to 2000, which was characterized by the reduction
      of tariff and nontariff barriers to trade, the removal of restrictions on
      international investment flows, and increasing intervention by the International
      Monetary Fund and World Bank on a wide range of economic and policy issues. While
      the evidence presented here does not prove that the policies associated with
      globalization were responsible for the deterioration in economic performance, it
      does present a very strong prima facie case that some structural and policy
      changes implemented during the last two decades are at least partly responsible
      for these declines.

PMID- 12067031
TI  - The future of the welfare state: crisis myths and crisis realities.
AB  - Accounts of the future of the welfare state are often presented in crisis terms.
      Some commentators identify globalization as a force that has already led to a
      major retreat by the state and is likely to lead to further downsizing of the
      public sector. Others see the future burden of an aging population as creating
      huge public expenditure pressures that can be countered only by increased
      parsimony in most areas of spending. Although both crisis scenarios contain
      elements of truth, analysis of recent public expenditure trends shows that both
      are substantially exaggerated as general representations of likely developments
      over the next two or three decades. However, unnoticed by most commentators, a
      real, longer-term crisis is beginning to make itself felt. This crisis arises, in
      part, from the demographic impact of a cultural transformation in the labor
      market, in progress for several decades. Extreme scenarios of possible
      consequences over the next 50 to 100 years include population implosion, mass
      migration, increasingly dangerous eruptions of right-wing populism, and,
      possibly, territorial conflict between developed and underdeveloped nations. This
      is not a crisis of the welfare state but rather a crisis for which the welfare
      state may be an essential part of the answer. The only way Western societies can
      lessen the future impact of the ongoing cultural transformation of the labor
      market is through the redesign of welfare state institutions to confront these
      new challenges.

PMID- 12067032
TI  - The globalization of capital, the welfare state, and old age policy.
AB  - A new political economy is shaping the lives of present and future generations of
      older people. The key change has been the move from the mass institutions that
      defined growing old in the period from 1945 through the late 1970s to the more
      individualized structures--privatized pensions, privatized health and social care
      -that increasingly inform the current period. The authors examine the role of
      international governmental organizations in promoting this trend, with examples
      drawn from the work of the World Bank, World Trade Organization, and Organization
      for Economic Cooperation and Development, and the relationship between
      international governmental organizations and the state. The article concludes
      with an assessment of the changes to citizenship that accompany globalization and
      the implications for political organization among older people themselves.

PMID- 12067033
TI  - The health care workforce in Los Angeles County and New York City: a comparison
      and analysis.
AB  - New York City and Los Angeles County have the largest health systems in the
      United States, but they differ significantly in structure. This study compares
      and analyzes the structural and workforce differences between the two. The health
      system in New York City is centered around its large hospitals, and as a result
      New York employs many more health workers than Los Angeles County, where the
      health system is centered around physician groups. Health care is a significant
      contributor to the economy of both areas, but a larger contributor to the economy
      in New York City.

PMID- 12067034
TI  - Does investor-ownership of nursing homes compromise the quality of care?
AB  - Quality problems have long plagued the nursing home industry. While two-thirds of
      U.S. nursing homes are investor-owned, few studies have examined the impact of
      investor-ownership on the quality of care. The authors analyzed 1998 data from
      inspections of 13,693 nursing facilities representing virtually all U.S. nursing
      homes. They grouped deficiency citations issued by inspectors into three
      categories ("quality of care," "quality of life," and "other") and compared
      deficiency rates in investor-owned, nonprofit, and public nursing homes. A
      multivariate model was used to control for case mix, percentage of residents
      covered by Medicaid, whether the facility was hospital-based, whether it was a
      skilled nursing facility for Medicare only, chain ownership, and location by
      state. The study also assessed nurse staffing. The authors found that investor
      owned nursing homes provide worse care and less nursing care than nonprofit or
      public homes. Investor-owned facilities averaged 5.89 deficiencies per home, 46.5
      percent higher than nonprofit and 43.0 percent higher than public facilities, and
      also had more of each category of deficiency. In the multivariate analysis,
      investor-ownership predicted 0.679 additional deficiencies per home; chain
      ownership predicted an additional 0.633 deficiencies per home. Nurse staffing
      ratios were markedly lower at investor-owned homes.

PMID- 12067035
TI  - Job stress and job dissatisfaction of home care workers in the context of health
      care restructuring.
AB  - Changes in the social organization of home care work due to health care
      restructuring have affected the job stress and job dissatisfaction of home care
      workers. This article reports the results of a survey of 892 employees from three
      nonprofit home care agencies in a medium-sized city in Ontario, Canada. Survey
      results are complemented by data from 16 focus groups with 99 employees. For the
      purposes of this study, home care workers include both office workers (managers,
      supervisors, coordinators, office support staff, and case managers) and visiting
      workers (nurses, therapists, and visiting homemakers). Focus group participants
      indicated that health care restructuring has resulted in organizational change,
      budget cuts, heavier workloads, job insecurity, loss of organizational support,
      loss of peer support, and loss of time to provide emotional laboring, or the
      "caring" aspects of home care work. Analyses of survey data show that
      organizational change, fear of job loss, heavy workloads, and lack of
      organizational and peer support lead to increased job stress and decreased levels
      of job satisfaction.

PMID- 12067036
TI  - Case studies of violations of workers' freedom of association: manufacturing
      workers.
AB  - As part of its report "Unfair Advantage: Workers' Freedom of Association in the
      United States under International Human Rights Standards," Human Rights Watch
      conducted a series of case studies in a dozen states, covering a variety of
      industries and employment sectors, analyzing the U.S. experience in the light of
      both national law and international human rights and labor rights norms.
      Presented here are the case studies of manufacturing workers.

PMID- 12067037
TI  - The end of the golden age of doctoring.
AB  - Eight interrelated reasons for the decline of the golden age of doctoring are
      discussed in this article. Major extrinsicfactors (generally outside the control
      of the profession) include (1) the changing nature of the state and loss of its
      partisan support for doctoring, (2) the bureaucratization (corporatization) of
      doctoring; (3) the emerging competitive threat from other health care workers;
      (4) the consequences of globalization and the information revolution; (5) the
      epidemiologic transition and changes in the public conception of the body; and
      (6) changes in the doctor-patient relationship and the erosion of patient trust.
      Major intrinsic factors are (7) the weakening of physicians' labor market
      position through oversupply; and (8) the fragmentation or weakening of the
      physicians, union (AMA). Despite the recent sociopolitical transformation of
      modern U.S. medicine, our thinking remains wedded to a now inadequate theoretical
      approach. A future sociology of the professions can no longer overlook now
      pervasive macrostructural influences on provider behavior (corporate dominance).
      Until these influences are appropriately recognized and incorporated in social
      analyses, most policies designed to restore the professional ideal have little
      chance of success.

PMID- 12067038
TI  - An innovative community-based approach to encourage breastfeeding among
      Hispanic/Latino women.

PMID- 12067039
TI  - Limiting the use of antibiotics in livestock: helping your patients understand
      the science behind this issue.

PMID- 12067040
TI  - Risk management strategies for the dietetics professional in long-term care.

PMID- 12067041
TI  - Sugar Association response to "Sugar and sugars: myths and realities".

PMID- 12067042
TI  - Impact your practice: communicate effectively online.

PMID- 12067043
TI  - Interpreting and using the dietary references intakes in dietary assessment of
      individuals and groups.
AB  - For individuals, a statistical approach is available to compare observed intakes
      to the EAR or AI (to assess adequacy), and the UL (to assess risk of excess). A
      more qualitative assessment of intakes involves comparison directly to the RDA to
      evaluate adequacy, but this is accurate only if long-term usual intake is known.
      For groups of people, the prevalence of inadequacy can usually be estimated as
      the proportion with intakes below the EAR, while the prevalence of potentially
      excessive intakes is estimated as the proportion above the UL. The accuracy of
      all assessments depends on unbiased and accurate intake estimates as well as a
      consideration of the effects of day-to-day variation in intake. Nutrition
      practitioners will find the new DRIs useful for assessing diets in a variety of
      settings. Computerized assessment systems will be important tools when
      incorporating these theoretical concepts into dietetic practice.

PMID- 12067044
TI  - The effects of physical and emotional status on adherence to a low-fat dietary
      pattern in the Women's Health Initiative.
AB  - OBJECTIVE: To examine whether the effects of physical and emotional status on
      adherance to a low-fat (20% energy) dietary pattern are mediated by participation
      in an intervention program (attending sessions and self-monitoring). DESIGN: The
      Baron and Kenny mediator model, a series of 4 regression analyses, was used to
      evaluate whether: a) physical and emotional status predicted program
      participation, b) program participation predicted dietary adherence, c) physical
      and emotional status factors predicted dietary adherence, and, ultimately d) the
      effects of physical and emotional status on dietary adherence were mediated by
      program participation. SUBJECTS/SETTING: Data from 13,277 postmenopausal women
      randomly assigned to the low-fat intervention arm of the Women's Health
      Initiative Dietary Modification Trial. INTERVENTION: The nutrition goals for
      women randomly assigned to the low-fat intervention were to reduce total fat
      intake to 20% or less of energy from fat and to consume 5 or more fruit/vegetable
      servings daily and 6 or more grain servings daily. MAIN OUTCOME MEASURES: Year 1
      program participation (degree of attending group sessions and submitting fat
      scores) and adherence to the low-fat dietary pattern (percent energy from fat) as
      predicted by baseline physical and emotional status (eight SF-36 Health Survey
      subscales). RESULTS: Participating in the dietary intervention program reduced
      (mediated) the negative effect of poorer mental health on dietary adherence by
      15%. Additional findings included that a 10% increase in physical functioning
      increased session attendance by 0.4% (P<.001) and a 10% increase in mental health
      predicted a decrease in percent energy from fat of 0.3% (P<.001). Program
      participation had a marked effect on dietary adherence: a 10% increase in session
      attendance predicted a 1.2% decrease in percent energy from fat (P<.001).
      APPLICATIONS/CONCLUSIONS: Understanding and using instruments to assess the
      physical and emotional status of a target population will help dietetic
      professionals promote healthful dietary change and maintenance.

PMID- 12067045
TI  - Increased fruit, vegetable and fiber intake and lower fat intake reported among
      women previously treated for invasive breast cancer.
AB  - OBJECTIVE: To describe the dietary intake patterns of women before and after
      breast cancer diagnosis. SUBJECTS AND SETTING: 3,084 women (age range 27 to 70
      years) who had been treated for early-stage breast cancer, who were free of
      recurrent disease, and who were willing to complete study questionnaires. DESIGN:
      A descriptive analysis of baseline demographic and lifestyle questionnaire data,
      including reported dietary intake data from women who have had breast cancer
      participating in a randomized, controlled dietary intervention trial. Outcomes
      include dietary intakes of high- and low-fat foods, fruits and vegetables, and
      whole grains. STATISTICAL ANALYSIS PERFORMED: Analyses included frequency of
      intake of selected food items, chi2 analysis to determine associations between
      reported intakes and demographic and personal characteristics, and logistic
      regression to assess odds of making more healthful changes. RESULTS: Women who
      have had breast cancer reported higher fruit, vegetable, and fiber-rich food
      intakes (58%, 60%, 38% more, respectively) and lower intakes of high-fat foods,
      including fast foods, after diagnosis. Those older than age 60 years were more
      likely to report no change in intake, including red meat (41%), vegetables (51%),
      and whole grains (62%). Odds ratios (OR) for more healthful diet choices varied
      by age and time since diagnosis. The longer the time since diagnosis the more
      likely women selected low-fat (vs high-fat) foods (OR 1.56, 95% confidence
      interval [CI] 1.16-2.09 for 3 to 4 years vs <1 year after diagnosis) and reduced
      added fats (OR 1.47, 95% CI 1.17-1.84 for 3 to 4 years vs <1 year after
      diagnosis). APPLICATIONS: Women who have had breast cancer report more healthful
      diet habits after diagnosis. Through nutrition education and counseling,
      dietetics professionals may be able to promote healthful and evidence-based
      eating habits among women previously treated for breast cancer.

PMID- 12067046
TI  - Changes in vegetable and fruit consumption and awareness among US adults: results
      of the 1991 and 1997 5 A Day for Better Health Program surveys.
AB  - OBJECTIVE: The purpose of this study is to assess population-based changes in
      vegetable and fruit consumption and psychosocial correlates. DESIGN: Two
      nationally representative random digit dial surveys conducted in 1991 and 1997;
      respondents were queried regarding consumption of and attitudes and knowledge
      about vegetables and fruit. SUBJECTS/SETTING: Respondents were 2,755 and 2,544
      adults (in 1991 and 1997, respectively) older than 18 years. STATISTICAL ANALYSIS
      PERFORMED: Vegetable and fruit consumption and message awareness were measured
      using weighted-only and regression model-adjusted analyses to assess changes.
      RESULTS: Mean vegetable and fruit consumption was significantly (P=.007) higher
      in 1997 than in 1991 using weighted-only analyses, but remained significant only
      for Hispanic (P=.03) and nonsmoker (P=.004) subgroups when adjusted for
      demographic shifts. Significantly higher percentages were found in the model
      adjusted analyses for those consuming 5 or more (daily servings (23.4% to 25.8%),
      message awareness (7.7% to 19.2%), and knowledge of the 5 A Day Program (2.0% to
      17.8%). APPLICATIONS/CONCLUSIONS: A significantly positive change in vegetable
      and fruit consumption occurred between 1991 and 1997 according to traditional
      methods of survey data analysis, but null findings resulted when the data were
      adjusted for demographic shifts. Nutrition professionals should continue
      targeting specific demographic subgroups with tailored interventions to move all
      Americans toward achievement of dietary guidelines for vegetable and fruit
      consumption.

PMID- 12067047
TI  - Is a tomato a fruit and a vegetable?

PMID- 12067048
TI  - Supplement use: is there any nutritional benefit?
AB  - OBJECTIVE: To examine the role of dietary supplements in improving total nutrient
      intakes in adults. DESIGN: Dietitian-administered 24-hour recalls (of intake
      including supplements) were conducted in 1997 and 1998. Supplement users were
      categorized into groups based on the types of supplements used and nutrient
      intake was examined. SUBJECTS: Using a multistage, stratified random sampling,
      1,530 Canadian adults aged 19 to 65 years were surveyed. STATISTICAL ANALYSES
      PERFORMED: Intakes from diet, supplements, and diet plus supplements were
      examined by age/gender stratification. RESULTS: Supplement users had dietary
      intakes, from food alone, similar to nonusers with mean intakes in some age/sex
      groups below the Recommended Daily Allowance (RDA)/Adequate Intake (AI) for iron,
      calcium, and folate. Multivitamin users had mean intakes (from diet plus
      supplement) of folate above the RDA and iron intakes also increased to RDA levels
      among women aged 19 to 50 years. Calcium supplement users had lower calcium and
      vitamin D intakes than nonusers from diet alone in some age/sex groups. Calcium
      tablets increased mean calcium intakes to AI levels among all age/sex groups.
      Many supplement users exceeded the new Upper Limits of safe intake; 47% in the
      case of niacin. APPLICATIONS: Supplements are commonly used and can help some
      persons adhere to Dietary Reference Intake recommendations concerning intake of
      folate, calcium, vitamin D. and iron. We found multivitamin users to have higher
      total intakes of folic acid, iron, calcium, and vitamin D. Also, targeted use of
      calcium supplements effectively enhanced intakes. However, concurrent vitamin D
      supplementation is important and awareness of product composition with respect to
      Upper Limits is essential.

PMID- 12067049
TI  - Inherent flaws in a method of estimating meal intake commonly used in long-term
      care facilities.
AB  - OBJECTIVE: To evaluate the accuracy of a method used to estimate nursing home
      residents' meal consumption, where the meal tray is assessed as a whole and
      assigned a value of 0%, 25%, 50%, 75%, or 100% consumed, under both routine and
      controlled conditions. SUBJECTS/SETTING: This study was conducted with certified
      nursing assistants at a 180-bed long-term-care facility in Miami, Fla. METHODS:
      Study 1 evaluated the method under routine conditions by comparing nursing
      assistants' estimates to actual meal consumption of 42 residents over 109 meals.
      A second study evaluated the method in a controlled setting where nursing
      assistants were free of disincentives and distractions that might contribute to
      inaccurate reporting. In a crossover design, nursing assistants estimated
      consumption on 4 manipulated trays under conditions of both immediate and delayed
      reporting. STATISTICAL ANALYSIS: An intraclass correlation coefficient and
      percent agreement were used to compare nursing assistants' estimates to weighed
      meal intakes. RESULTS: Under routine conditions, the intraclass correlation
      coefficient between nursing assistants' estimates and the actual resident meal
      consumption was weak at 0.464 (95% confidence interval=0.146 to 0.664). The
      correct estimate was recorded 44% of the time. In the controlled setting, the
      nursing assistants' estimates for percent consumed agreed with weighed intakes
      44% and 38% of the time with immediate and delayed recording, respectively.
      APPLICATIONS/CONCLUSIONS: This 1-step method of estimating meal consumption with
      an overall percentage is not sufficiently accurate to identify residents who are
      eating less than 75% of most meals.

PMID- 12067050
TI  - Family caregiver training is needed to improve outcomes for older adults using
      home care technologies.
AB  - Family caregivers, although uncompensated, provide daily care for more than 75%
      of the older adults who are dependent on home care technologies such as home
      enteral nutrition. The high complication rates and poor outcomes seen in older
      adults suggest that being an effective caregiver requires specialized training in
      home care technologies, and dietitians need to be more actively involved in
      discharge planning and follow-up home care. The level of knowledge and skill
      mastery required for technology-dependent care, along with the chronic, intensive
      nature of family caregiving and the disruptions in caregivers' daily lives, lead
      to negative emotional and physical consequences that may interfere with
      caregivers' ability to do caregiving well. Recognizing that care recipients and
      caregivers are underserved populations, dietitians should develop their
      professional competencies and expand their roles in technology-dependent home
      care. Dietitians can thereby contribute to better outcomes for both family
      caregivers and older home care recipients.

PMID- 12067051
TI  - Nutrition support at the end of life: opinions of Louisiana dietitians.
AB  - The purpose of this study was to determine the opinions of registered dietitians
      in Louisiana concerning nutrition support at the end of life. A questionnaire was
      mailed to the 777 active members of the Louisiana Dietetic Association. Questions
      addressed 3 issues: removal of nutrition support, the role of patients and family
      in decision making, and the role of the dietitian in decisions to use nutrition
      support for the terminally ill. A mean composite score was determined for each
      category. Kruskal-Wallis 1-way ANOVA was conducted on the composite scores to
      determine differences in responses by age, years of practice, and area of current
      practice. At least 60% of the respondents agreed with foregoing, withholding, or
      withdrawing nutrition support at the end of life. Most of the dietitians agreed
      that the patient or family is more qualified than the health care professional to
      make decisions about nutrition support at the end of life. More than 95% of the
      dietitians agreed that the dietitian should be involved in the decision-making
      process. However, only 50% of the dietitians felt fully qualified to provide the
      information needed to help a patient or family make the decision about nutrition
      support at the end of life. Differences of opinions about the removal of
      nutrition support were found by age, number of years of practice, and current
      area of practice. Results from this study may encourage dietitians to explore
      their own attitudes and seek continuing education on ethical dilemmas to enable
      them to make better decisions, provide better care, and become better patient
      advocates.

PMID- 12067052
TI  - Support for dietitians working in nutrition support: a discussion on how RDs can
      prepare themselves to advise families of patients at the end-of-life.

PMID- 12067053
TI  - Dietary intake assessed by the Nutrition Screening Initiative Level II Screen is
      a sensitive but not a specific indicator of nutrition risk in older adults.

PMID- 12067054
TI  - Dietary calcium intake and supplement use among older African American, white,
      and Native American women in a rural southeastern community.

PMID- 12067055
TI  - Use of surrogate respondents in a case control study of dietary risk factors for
      Alzheimer's disease.

PMID- 12067056
TI  - Dietetics interns at geographically remote supervised practice sites find a
      listserv to be a useful information-sharing tool that fosters independent
      learning.

PMID- 12067057
TI  - The nutritional consequences of flavored-milk consumption by school-aged children
      and adolescents in the United States.

PMID- 12067058
TI  - Acceptability of reduced-fat brownies by school-aged children.

PMID- 12067059
TI  - Approaches to ethical decision making.

PMID- 12067060
TI  - Thyroid cell proliferation in response to forced expression of gap junction
      proteins.
AB  - Gap junctions are known to play a role in the control of cell proliferation, and
      connexins (Cx) are considered to be tumor suppressors. However, the effects of Cx
      on cell proliferation are dependent on the Cx which is expressed and on the cell
      type under consideration. We previously found that restoration of cell-to-cell
      communication by stable transfection of two independent thyroid-derived cell
      lines, FRTL-5 and FRT cells, with the Cx32 gene induced a marked reduction of
      their proliferation rate. This study aimed i) at determining whether Cx43, which
      is coexpressed with Cx32 by thyroid epithelial cells, exerts the same action as
      Cx32 on cell proliferation and ii) at identifying alterations of the cell cycle
      control system that might account for the Cx32-induced proliferation slowdown in
      thyrocytes. In contrast with previous data on different epithelial cell types, we
      report that restoration of intercellular communication in FRTL-5 and FRT cells by
      stable expression of Cx43 did not modify their proliferation properties. Cell
      cycle analyses revealed that the Cx32-induced proliferation slow-down was related
      to a lengthening of the G1 phase. The level of expression of two regulatory
      proteins of the Cip/Kip cyclin-dependent kinase inhibitor family, p27kip1 and
      p2cip1, was increased in the two cell lines expressing Cx32. In conclusion, Cx32
      and Cx43, physiologically coexpressed by thyrocytes, have a differential impact
      on thyroid cell proliferation in vitro. The cyclin-dependent kinase inhibitors,
      p27kip1 and p21cip1 might represent cell cycle effectors relaying the down
      regulatory effect of Cx32 on the proliferation of thyroid epithelial cells.

PMID- 12067061
TI  - Organization and formation of the tight junction system in human epidermis and
      cultured keratinocytes.
AB  - Occludin and several proteins of the claudin family have been identiried in
      simple epithelia and in endothelia as major and structure-determining
      transmembrane proteins clustered in the barrier-forming tight junctions (TJ),
      where they are associated with a variety of TJ plaque proteins, including protein
      ZO-1. To examine whether TJ also occur in the squamous stratified epithelium of
      the interfollicular human epidermis we have applied several microscopic and
      biochemical techniques. Using RT-PCR techniques, we have identiried mRNAs
      encoding protein ZO-1, occludin and claudins 1, 4, 7, 8, 11, 12, and 17 in both
      tissues, skin and cultured keratinocytes, whereas claudins i and 10 have only
      been detected in skin tissue. By immunocytochemistry we have localized claudin-1,
      occludin and protein ZO-1 in distinct plasma membrane structures representing
      cell-cell attachment zones. While claudin-1 occurs in plasma membranes of all
      living cell layers, protein ZO-1 is concentrated in or even restricted to the
      uppermost layers, and occludin is often detected only in the stratum granulosum.
      Using electron microscopy, typical TJ structures ("kissing points") as well as
      some other apparently related junctional structures have been detected in the
      stratum granulosum, interspersed between desmosomes. Modes and patterns of TJ
      formation have also been studied in experimental model systems, e.g., during
      wound healing and stratification as well as in keratinocyte cultures during Ca2+
      induced stratification. We conclude that the epidermis contains in the stratum
      granulosum a continuous zonula occludens-equivalent structure with typical TJ
      morphology and molecular composition, characterized by colocalization of
      occludin, claudins and TJ plaque proteins. In addition, cell-cell contact
      structures and certain TJ proteins can also be detected in other epidermal cell
      layers in specific cell contacts. The pattern of formation and possible functions
      of epidermal TJ and related structures are discussed.

PMID- 12067062
TI  - CALbeta, a novel lipocalin associated with chondrogenesis and inflammation.
AB  - We have previously demonstrated the association of the chicken lipocalin Ex-FABP
      with cartilage formation and inflammatory responses as a marker of these
      processes (Descalzi Cancedda et al., Biochim. Biophys. Acta 1482, 127-135, 2000).
      Here we report the isolation and characterisation of a new lipocalin gene laying
      upstream the Ex-FABP, thus representing the second member of a possible genomic
      cluster. This gene contains an open reading frame coding for a polypeptide of
      about 19 kDa. The amino-acid sequence revealed a conserved lipocalin secondary
      structure. Tissue distribution of the protein in developing embryos showed a
      preferential expression in the heart although mRNA transcripts could be detected
      also in muscle, lung and liver. The lowest expression was observed in the
      stomach, brain and skin. During endochondral formation of long bones, the protein
      is differentially distributed, as the transcripts, evidenced in the tibia by in
      situ hybridisation, are present in the hypertrophic cone of the cartilage and
      mostly absent in the area of the proliferating chondrocytes. Such developmental
      regulation was observed also in vitro in cultured chondrocytes where the
      transcripts were barely detectable in dedifferentiated cells but highly expressed
      in hypertrophic chondrocytes. The protein was also significantly induced by
      lipopolysaccharide stimulation of chondrocytes, indicating a possible involvement
      in acute phase response. Raising specific antibodies in a rabbit allowed
      validating, at the protein level, all the transcriptional data. Moreover, we
      gained evidence that the protein is actively secreted in the extracellular matrix
      surrounding the chondrocytes. Because of its peculiar expression in cartilage,
      this new protein was named chondrogenesis-associated lipocalin beta (thereafter
      referred to as CAL beta). The close similarity between Ex-FABP and CAL beta
      expression patterns supports the hypothesis of a genomic organisation in a
      cluster where both genes could be co-ordinately regulated.

PMID- 12067063
TI  - The SNAREs vti1a and vti1b have distinct localization and SNARE complex partners.
AB  - Two mammalian proteins, vtila and vtilb, are homologous to the yeast Q-SNARE
      Vtilp which is part of several SNARE complexes in different transport steps. In
      vitro experiments suggest distinct functions for vtila and vtilb. Here we
      compared the subcellular localization of endogenous vtila and vtilb by
      immunofluorescence and immuno-electron microscopy. Both proteins had a distinct
      but overlapping localization. vtila was found predominantly on the Golgi and the
      TGN, vtilb mostly on tubules and vesicles in the TGN area and on endosomes. vti1a
      coimmunoprecipitated with VAMP-4, syntaxin 6, and syntaxin 16. These four SNAREs
      could assemble into a SNARE complex of conserved structure because one SNARE
      motif of each subgroup is present. vtila-beta, VAMP-4, syntaxin 6, and syntaxin
      16 are coenriched with small synaptic vesicles and with clathrin-coated vesicles
      isolated from rat brain synaptosomes. Therefore, this SNARE complex may have a
      role in synaptic vesicle biogenesis or recycling.

PMID- 12067064
TI  - Perturbation of gastric mucosa in mice expressing the temperature-sensitive
      mutant of SV40 large T antigen. Potential for establishment of an immortalised
      parietal cell line.
AB  - Gastric parietal cells have a unique secretory membrane system that undergoes a
      profound transformation when the parietal cell is stimulated to secrete acid.
      Understanding this process has been hindered by the lack of an immortalised
      parietal cell line. Here we have explored a strategy for the development of a
      parietal cell line by the generation of transgenic mice bearing the temperature
      sensitive mutant of the SV40 large T antigen (SV40 tsA58) under the control of
      the regulatory sequences of the gastric H+/K+ ATPase beta-subunit (H/Kbeta
      tsA58). Three H/ Kbeta-tsA58 transgenic mouse lines were established, namely 218,
      224 and 228, all of which expressed the tsA58 T antigen in the gastric mucosa.
      Unexpectedly, the gastric mucosae of all lines were hypertrophic indicating that
      the temperature-sensitive large T antigen was partially active at 37 degrees C.
      Immunofluorescence together with light and electron microscopic studies revealed
      that mature parietal and zymogenic cells were absent in H/Kbeta-tsA58 transgenic
      lines 218 and 224, and small undifferentiated cells were the dominant cell type
      in the gastric units. On the other hand, a few mature parietal cells were
      detected in line 228 together with an increased proportion of undifferentiated
      cells and, normally rare, pre-parietal cells. As line 228 represented a rich
      source of pre-parietal cells, gastric cells from line 228 were isolated and
      cultured at 33 degrees C, the permissive temperature for tsA58. Gastric
      epithelial cells, expressing the T antigen, were maintained in culture for over 6
      weeks. Upon a temperature shift to 39 C the cultured gastric cells developed
      characteristics of differentiated parietal cells, including the presence of a
      nascent canaliculus and dramatically increased production of the gastric H+/K+
      ATPase beta-subunit. Therefore, this system shows the potential to generate an
      immature parietal cell line that can be induced to differentiate in vitro.

PMID- 12067065
TI  - P53-dependent expression of the stress-induced protein (SIP).
AB  - The mouse stress-induced protein (SIP) mRNA is activated in the pancreas with
      acute pancreatitis and in several cell lines in response to various stress
      agents. The SIP gene is alternatively spliced, generating two proteins (SIP'8 and
      SIP27). Both proteins, located mainly in the nucleus, promote cell death when
      overexpressed in vitro. We show that induction by stress agents of the expression
      of SIP18 and SIP27 mRNAs, observed in human- and mouse-derived cell lines, is
      absent from cells with deleted, mutated or inactive p53, suggesting that
      regulation of SIP gene expression is dependent on p53. That hypothesis is
      consistent with the presence of a functional p53-response element within the
      promoter region of the mouse SIP gene and confirmed by the induction of SIP mRNA
      expression in mouse embryo fibroblasts upon activation of a p53-dependent pathway
      by transfection with rasV12 or rasV12/E1A. In conclusion, SIP being a
      proapoptotic gene induced through p53 activation could be a stress-induced gene
      with antitumour properties.

PMID- 12067066
TI  - Cytoplasmic intermediate filament protein expression in tunicate development: a
      specific marker for the test cells.
AB  - The urochordate Ciona intestinalis is a well established system for embryological
      studies, and large scale EST sequences begin to emerge. We cloned five
      cytoplasmic intennediate filament (IF) cDNAs and made specific antibodies to the
      recombinant proteins. Self-assembly studies and immunofluorescence microscopy
      were used to study these proteins and their distribution. Confirming and
      extending previous studies in Styela, we found that Ciona protein IF-A is
      expressed in muscle and forms homopolymeric filaments while proteins IF-C and IF
      D, which form only obligatory heteropolymeric filaments, resemble a keratin pair
      exclusively found in the entire epidermis. Protein IF-B and the new protein IF-F
      potentially reflect tunicate-specific IF proteins. They are found in the entire
      internal epithelia including the neural gland. We also extended the analysis to
      earlier developmental stages of Ciona. Protein IF-A is expressed in muscle from
      larval stages, whereas proteins IF-C and IF-D are found only in the tail
      epidermis. Protein IF-F is detected abundantly in the test cells of eggs, embryos
      and premetamorphic larvae. Our studies show that IF proteins could prove very
      useful markers in the study of cell fate determination in Ciona. They also
      support previous findings on the evolutionary relationships of different IF
      proteins. Non-vertebrate chordates have IF proteins which represent orthologs of
      vertebrate type I to III proteins, but also IF proteins that do not seem to fit
      into these classes. However, the intron positions of all tunicate IF genes are
      conserved with vertebrate type I to III genes, pointing to a common evolutionary
      origin.

PMID- 12067067
TI  - Proteolytic cleavage of molecules involved in cell death or survival pathways: a
      role in the control of apoptosis?
AB  - Proteolytic modification of certain key regulatory molecules involved in
      apoptotic and prosurvival pathways may be a feature of the control of programmed
      cell death. Four molecules of the Bd-2 family (BID, Bcl-2, Bax, Bcl-X(L)) have
      been reported to be deaved during apoptosis, as has a cellular inhibitor of
      apoptosis (XIAP). Two proteins involved in NF-kappaB activation, RIP and TRAF1,
      are cleaved during apoptosis induced by agents that activate both pathways.
      MEKK1, a molecule involved in a protein kinase stress signaling cascade that
      contributes to apoptosis and NF-kappaB activation, also undergoes cleavage. In
      each case, the cleavage products may result in the inactivation of a former
      function or the gaining of a new function, thus contributing to the delicately
      balanced regulation of apoptosis.

PMID- 12067068
TI  - Involvement of the nuclear matrix in the control of skeletal genes: the NMP1
      (YY1), NMP2 (Cbfa1), and NMP4 (Nmp4/CIZ) transcription factors.
AB  - The functional role of the osteoblast nuclear matrix has been a matter of
      supposition. Its presumed function as an architectural agent of transcription
      derives primarily from the low solubility of nuclear matrix proteins and their
      typical localization into discrete subnuclear domains. In addressing how the
      nuclear matrix regulates skeletal genes, the authors compare Nmp4, Cbfal, and YY1
      for the purpose of profiling osteoblast nuclear matrix transcription factors. All
      three proteins contribute to the transcription of ECM genes and partition into
      the osteoblast nuclear matrix via a nuclear matrix targeting domain. The authors
      propose that osteoblast nuclear matrix transcription factors involved in ECM
      regulation generally have the capacity to alter DNA geometry and reciprocally
      respond to DNA as an allosteric ligand. This may allow these proteins to adapt to
      the local nuclear architecture and generate the pattern of regulation specified
      by that architecture via unmasking of the appropriate transactivation domains.
      Osteoblast nuclear matrix transcription factors may also act as transcriptional
      adaptor molecules by supporting the formation of higher order protein complexes
      along target gene promoters. The genes encoding all three proteins considered
      here have trinucleotide repeat domains, although the significance of this is
      unclear. There is no canonical nuclear matrix binding motif, but finger-like
      structures may be suited for anchoring proteins to discrete subnuclear domains.
      Finally, the ability to leave the osteoblast nuclear matrix may be as important
      to the function of some nuclear matrix transcription factors as their association
      with this subcompartment.

PMID- 12067069
TI  - Regulation of osteoblast growth by interactions between transforming growth
      factor-beta and 1alpha,25-dihydroxyvitamin D3.
AB  - Osteoblast growth and differentiation encompass a series of events including
      proliferation, changes in cell shape, and expression of the markers specific for
      osteoblast phenotype. Both transforming growth factor-beta (TGF-beta) and
      1alpha,25-dihydroxyvitamin D3 (1alpha,25[OH]2D3) are effective in regulating
      osteoblast proliferation, differentiation, bone matrix maturation and cell
      specific gene expression. Although there is some degree of controversy regarding
      the influences on osteoblasts in vitro, it is generally agreed that TGF-beta
      stimulates osteoblast proliferation and growth, and inhibits the expression of
      the markers characteristic of the osteoblast phenotype such as osteocalcin. In
      contrast, 1alpha,25(OH)2D3 causes inhibition of the proliferation of osteoblasts,
      arrests their growth, and stimulates expression of specific markers. In many
      studies, complex interactions have been demonstrated between TGF-beta and
      1alpha,25(OH)2D3 modulating their receptor expression, synthesis, and effects on
      osteoblast-specific gene expression. The cooperative actions of TGF-beta and
      1alpha,25(OH)2D3 can be synergistic or antagonistic. It has recently been
      established that Smad proteins that transduce signals downstream the TGF-beta
      stimulation may mediate the crosstalk between TGF-beta and 1alpha,25(OH)2D3
      signaling. Future studies should focus on the explanation of the molecular basis
      of these interactions and the in vivo consequences of the regulation of
      osteoblast growth and differentiation by TGF-beta and 1alpha,25(OH)2D3.

PMID- 12067070
TI  - Angiostatic proteins and peptides.
AB  - Angiogenesis, or the formation of new vasculature out of preexisting capillaries,
      is a sequence of events that is essential in the normal physiological processes
      of tissue growth and in a broad spectrum of pathologies. The diseases in which
      angiogenesis plays a key role are divided into diseases that are characterized by
      hypoxia/ ischemia and diseases that are dependent on neovascularization. The
      formerpathologies may benefit from therapeutic angiogenesis stimulation. This
      review concentrates on the different strategies to inhibit angiogenesis in
      diseases that are characterized by excessive angiogenesis, for example, cancer,
      arthritis, diabetic retinopathy, and inflammatory diseases. These diseases are
      dependent on the development of newvasculature, and hence, a large variety of
      different strategies to inhibit angiogenesis are underwayin laboratories
      throughout the world. At present, over250 angiogenesis inhibitors are described,
      and approximately half of them display activity in in vivo models. A large
      percentage of these molecules are natural, nonnatural, or synthetic so-called
      small molecules. Others are of protein origin, either endogenous or exogenous by
      nature. The authors highlight the current knowledge on the development of
      angiostatic proteins and peptides and their potential in the treatment of
      disease.

PMID- 12067072
TI  - Health is a budget priority--its funding needs to be restored.

PMID- 12067071
TI  - Do welfare caseload declines make the Medicaid risk pool sicker?
AB  - Declining welfare caseloads may lead to a sicker population remaining in the
      Medicaid program, which could increase per enrollee costs and the level of
      adequate capitation rates. Using data from the 1997 National Survey of America's
      Families for adults and children, we examine differences in health status and
      utilization among welfare recipients and welfare leavers who did and did not
      retain Medicaid. We adjust utilization differences for insurance status and
      factors often used to adjust capitation rates. We conclude that declining welfare
      caseloads likely will result in a sicker and more expensive adult Medicaid risk
      pool.

PMID- 12067073
TI  - Financial risk sharing with providers in health maintenance organizations, 1999.
AB  - The transfer of financial risk from health maintenance organizations (HMOs) to
      providers is controversial. To provide timely national data on these practices,
      we conducted a telephone survey in 1999 of a multi-staged probability sample of
      HMOs in 20 of the nation's 60 largest markets, accounting for 86% of all HMO
      enrollees nationally. Among those sampled, 82% responded. We found that HMOs'
      provider networks with physicians, hospitals, skilled nursing homes, and home
      health agencies are complex and multi-tiered Seventy-six percent of HMOs in our
      study use contracts for their HMO products that involve global, professional
      services, or hospital risk capitation to intermediate entities. These
      arrangements account for between 24.5 million and 27.4 million of the 55.9
      million commercial and Medicare HMO enrollees in the 60 largest markets. While
      capitation arrangements are particularly common in California, they are more
      common elsewhere than many assume. The complex layering of risk sharing and
      delegation of care management responsibility raise questions about accountability
      and administrative costs in managed care. Do complex structures provide a way to
      involve providers more directly in managed care, or do they diffuse authority and
      add to administrative costs?

PMID- 12067074
TI  - Is healthy competition healthy? New evidence of the impact of hospital
      competition.
AB  - Competition among hospitals is commonly regarded as inefficient due to the
      medical arms race phenomenon, but most evidence for this hypothesis predates the
      Medicare prospective payment system and preferred provider legislation. Recent
      studies indicate hospital competition reduces costs and prices, but nearly all
      such research has focused on California. We add to the body of literature that
      analyzes the effects of competition in hospital markets. Using data from the
      state of Washington, we show that hospitals assume more risk in competitive
      markets by being more likely to accept prospective payment arrangements with
      insurers. If the arrangement is retrospective, the hospital is more likely to
      offer a discount as the number of competing hospitals increases. Both findings
      indicate that competitive forces operate the same in hospital markets as in most
      others: as the number of competitors increases, prices decrease and market power
      shifts from the suppliers to purchasers. The medical arms race hypothesis that
      favors more concentrated hospital markets no longer appears to be valid.

PMID- 12067075
TI  - Doing "good" vs. doing "well": the role of nonprofits in society.
AB  - Nonprofit organizations play a unique role in American life. However, they cannot
      exist alone; they have a complex, interdependent relationship with the economy's
      two other sectors-business and government. Driving the success of both for-profit
      and nonprofit organizations is the corporate board. This column explores the
      dynamics of boards, the connections among the three sectors, and our nation's
      growing reliance on nonprofits.

PMID- 12067076
TI  - Use of resident-origin data to define nursing home market boundaries.
AB  - Previous studies of nursing home markets have assumed that a nursing home's
      market is coincident with the boundaries of the county in which it is located. We
      test this assumption by using the zip code of residence for Medicare
      beneficiaries admitted into a nursing home in New York state in the periods 1992
      93 and 1996-97. We find that nursing homes located in urban areas have markets
      that are a fraction of the size of the county in which they are located. We
      calculate the Herfindahl-Hirschman Index (HHI) to measure the competitiveness of
      each nursing home's market. This shows that nursing home markets tend to be more
      concentrated than those that result from assuming countywide markets. These
      results suggest that studies of nursing home markets should not use counties as
      markets.

PMID- 12067077
TI  - The financial experience of hospitals with HMO contracts: evidence from Florida.
AB  - In this paper, we report results from the first study to systematically examine
      trends in the financial experience of hospitals with health maintenance
      organization (HMO) contracts. The longitudinal analysis (1990 through 1997)
      focused on hospitals in Florida. Hospital operating margins for HMO contracts
      grew tighter toward the end of the study period when the median margin was less
      than 1%. Teaching hospitals had operating margins that on average were below that
      of their nonteaching counterparts. The continued growth of HMOs and other managed
      care entities may have important implications for the future financial viability
      of U.S. hospitals.

PMID- 12067078
TI  - A guide to comparing health care expenditures in the 1996 MEPS to the 1987 NMES.
AB  - Substantial changes in the organization, delivery, and financing of health care
      over the last decade, combined with data collection and methodological
      improvements in the 1996 Medical Expenditure Panel Survey (MEPS), pose special
      challenges in comparing expenditure estimates in MEPS with those in the 1987
      National Medical Expenditure Survey (NMES). The 1987 NMES used charges as its
      fundamental expenditure concept, whereas the 1996 MEPS used actual payments as
      its expenditure measure. In spite of these differences, researchers and
      policymakers will want to be able to analyze trends in health care expenditures
      using these two surveys. We discuss these issues in detail and present a simple,
      straightforward adjustment method that can be applied to the 1987 NMES public use
      expenditure data to improve comparability to the MEPS. We base this adjustment
      method on an analysis of provider-reported payment data collected in NMES. We
      present several examples of the application of this method that illustrate the
      importance of the adjustments for analyses of trends in health care spending.

PMID- 12067080
TI  - Persistent eradication of Helicobacter pylori after systemic politherapy
      associated with periodontal pockets treatment with metronidazole and calcium
      sulphate.
AB  - The sensitivity of H. Pylori to antibiotic treatment is well known. Politherapy
      (omeprazole or pantoprazole or ranitidine, amoxicillin and/or azithromycin and/or
      clarithromycin, metronidazole and bismuth citrate) notably changed the percentage
      of H. pylori eradication but rarely resolutive. Periodontal pockets treatment
      with topic metronidazole, calcium sulphate and potassium sulphate resulted active
      against bacteria included in periodontal pockets leading to a long-term H. pylori
      eradication (two years follow-up).

PMID- 12067079
TI  - A new method for diagnosing fever of unknown origin (FUO) due to infection of
      muscular-skeletal system in elderly people: leukoscan Tc-99m labelled
      scintigraphy.
AB  - Twenty patients affected by fever of unknown origin (FUO), due to a likely
      infection of the muscular or skeletal tissues, were studied by a Total Body scan
      with a monoclonal antibody fragment (Leukoscan) labelled with Tc-99m. The
      diagnostic procedure helped reach a final diagnosis in 8 out of the 20 patients
      because it identified the focus of the infection of the muscles or bones in joint
      proximity. Our data show that Leukoscan deserves to become a first line
      diagnostic procedure in the diagnostic algorithm for the evaluation of patients
      with FUO.

PMID- 12067081
TI  - Nebulized tobramycin in patients with chronic respiratory infections during
      clinical evolution of Wegener's granulomatosis.
AB  - Aminoglycosides are effective against Pseudomonas aeruginosa but with intravenous
      administration there are only very low concentrations achieved in sputum;
      therefore in order to obtain therapeutic levels in patients with endobronchial
      infections should be administered high doses with increased likelihood to produce
      both nephrotoxic and ototoxic effects. Direct aerosol delivery of aminoglycosides
      to the lower respiratory tract has the advantage to achieve high antibiotic
      sputum concentrations in the infected area with reduced risk of systemic toxic
      reactions because of minimal absorption into the circulation. Nowadays, except
      for patients suffering from cystic fibrosis and bronchiectasis, the
      administration of antibiotics through inhalers is not very much in use. The aim
      of this study was to administer nebulized tobramycin in chronic respiratory
      infections developed during the evolution of Wegener's Granulomatosis in order to
      obtain data concerning the safety and efficacy of inhaled aminoglycosides. The
      results obtained underlined an improvement in FEV1, FEF75 and PaO2. The
      aerosolized tobramycin administered in 300 mg doses three times per day for four
      weeks, showed itself to be effective and safe, not causing any undesirable
      clinical or microbiological side-effects. Moreover, a long term treatment has
      been shown to control the Pseudomonas aeruginosa infection on the bronchial
      system in Wegener's granulomatosis and reduce the frequency of exacerbations in
      chronic patients.

PMID- 12067082
TI  - Antihistamines and the torsade de point in children with allergic rhinitis.
AB  - Allergic rhinitis (AR) is a very common disease, occurring in approximately 10%
      of children and up to 20% of adolescents. It is often underdiagnosed and its
      importance as a cause of morbidity is also underestimated, especially in
      asthmatic children. It has been estimated that 75% of asthmatic children suffer
      from AR, and its prevalence has increased during the last years, due to changes
      in environmental factors. AR may be a cause of serious discomfort for the child
      as well as for the family. AR may cause several complication, including serous
      otitis media, abnormal facial development with orthodontic problems, eustachian
      tube dysfunction and sinusitis. The frequent association of paranasal sinusitis
      in children with asthma has been observed and sinusitis has been considered a
      contributing factor in bronchial asthma Second-generation antihistamines are the
      golden therapy for AR. However, reports of potentially life-threatening
      dysrhythmias, specifically torsades de pointes, were described. In conclusion, we
      comment the in vitro inhibition of several ion channels, in particular
      predisposing the heart to dysrhythmias by terfenadine and astemizole. In this
      paper we examine recent reports on safety of both cetirizine and loratadine.

PMID- 12067083
TI  - Intra-articular analgesia following arthroscopic surgery of the shoulder.
AB  - Shoulder surgery is very often followed by severe postoperative pain. Loco
      regional anaesthesia has greatly contributed as a solution of this problem.
      Nevertheless most of surgery is still performed under general anaesthesia. In
      this case many different methods have been proposed in order to mitigate
      postoperative pain. Intra-articular administration of local anaesthetics after
      shoulder surgery is not yet in routinely clinical practice. In this study
      efficacy of intra-articular administration of Ropivacaine versus Bupivacaine has
      been evaluated. Analysis of results showed both drugs to share the same
      effectiveness within four hours postoperatively. In subsequent period (6-24
      hours) Ropivacaine demonstrated to provide a statistically significant better
      postoperative pain relief. Furthermore Ropivacaine group patients needed
      postoperative analgesics to a lesser extent than Bupivacaine group. The long
      losting satisfactory level of analgesia, particularly with Ropivacaine, could
      recommend the use of intra-articular analgesia even for day-hospital or one-day
      surgery procedures.

PMID- 12067084
TI  - Effect of acupuncture in the treatment of seasonal allergic rhinitis: a
      randomized controlled clinical trial.
AB  - The clinical efficacy and safety of acupuncture in the treatment of Seasonal
      Allergic Rhinitis (SAR) was evaluated by employing a two-phase crossover single
      blind clinical trial. Thirty subjects were randomly assigned to two groups with
      17 and 13 subjects respectively and treated with real or sham acupuncture (three
      times per week) for four consecutive weeks and then a crossover for treatments
      for a further four weeks without a washout period. The administration of real
      acupuncture treatment was guided by a syndrome differentiation according to
      Chinese Medicine Theory. Subjects were assessed by various criteria before,
      during and after the treatments. Outcome measures included subjective symptom
      scores using a five-point scale (FPS), relief medication scores (RMS) and adverse
      effect records. Twenty-six (26) subjects completed the study. There was a
      significant improvement in FPS (nasal and non-nasal symptoms) between the two
      types of acupuncture treatments. No significant differences were shown in RMS
      between the real acupuncture treatment group and the sham acupuncture treatment
      group. No side effects were observed for both groups. The results indicate that
      acupuncture is an effective and safe alternative treatment for the management of
      SAR.

PMID- 12067085
TI  - Anti-abortive effect of Radix scutellariae and Rhizoma atractylodis in mice.
AB  - The objective of this study is to investigate the significance of natural killer
      (NK) cells and interleukin-2 in uterus in the early embryo loss (or resorption),
      and to elucidate the immunological modulation of maternal-fetal interface with
      Chinese herbal medicine Radix scutellariae (huang qin) and Rhizoma atractylodis
      (bai zhu). Lipopolysaccharide (LPS) was given via the tail vein to induce
      abortion in mice at day 7 of gestation. Uterine NK cells and IL-2 contents were
      analyzed by immunohistochemistry and enzyme linked immunosorbent assay (ELISA),
      respectively. The number of NK cells was found to be much higher (mean = 180 +/-
      39) in the decidua of LPS-treated abortion mice. But when the Chinese herbal
      medicine was used to prevent LPS-induced abortion, less NK cells (mean = 11 +/-
      4) were counted (p < 0.01). The mean value of IL-2 in LPS-treated mice was 5.25
      +/- 2.5938 pg/mg protein, higher than (p < 0.05) that of the herb prevention
      group, which was only 1.86 +/- 0.9789 pg/mg protein. The results therefore
      indicate that the increase of NK cells in the decidua and IL-2 contents in the
      uterus in LPS-treated mice is closely related to the embryo loss, and that the
      Chinese herbal medicine prescription composed of Radix scutellariae and Rhizoma
      atractylodis has an anti-abortive effect through inhibition of maternal-fetal
      interface immunity.

PMID- 12067086
TI  - Liver regeneration enhanced by orally administered ursodesoxycholic acid is
      mediated by immunosuppression in partially hepatectomized rats.
AB  - The relationship of liver regeneration to immunoactivity was examined after
      ursodesoxycholic acid (UDCA) administration to partially (about 66%)
      hepatectomized rats. The UDCA was given orally. Liver regeneration was evaluated
      by the hepatocyte mitotic index (MI) and immunoactivity by natural killer cell
      (NK) activity in the blood. When UDCA 12.5 mg/kg/day was administered, a
      significant increase in the MI was observed 2 and 3 days after hepatectomy, and
      the MI response 2 days after bepatectomy tended to be dose-dependent in the range
      of 0-25 mg/kg/day. NK activity was decreased 2 days after hepatectomy when UDCA
      was given, and a significant correlation between MI and NK activity was obtained.
      The increase in MI and decrease in NK activity was blocked completely or
      partially (respectively) by interleukin-2 administration. It was also noted that
      UDCA did not affect serum parameters indicating liver and kidney function. These
      findings suggest that liver regeneration can be modified by orally administered
      UDCA through a change in immunoactivity.

PMID- 12067088
TI  - A controlled trial on acupuncture for chronic neck pain.
AB  - To evaluate the efficacy of Chinese medicine (CM) acupuncture for chronic neck
      pain (CNP), a single blind, controlled, crossover, clinical trial was undertaken.
      Twenty-nine volunteers with CNP were randomly recruited into two groups. Both
      groups received two phases of treatment with a washout period between the two
      phases. Group A (14 volunteers) received CM acupuncture in the first phase and
      sham acupuncture in the second, while Group B (15 volunteers) received sham in
      the first and real in the second. CM acupuncture was individualized and consisted
      of nine sessions on both local and distal points. Manual twisting of the needle
      was applied on all points plus strong electrical stimulation of distal points in
      CM acupuncture. Sham acupoints (lateral to the real) and sham (weak) electrical
      stimulation was used in the control group. Comparison of subjective and objective
      measures between the two groups was made at different periods, including
      baseline, after each phase of treatment, after washout, and after the 16th week
      follow-up. The subjective measures included pain intensity, duration per day,
      analgesic medication count, visual analogue scales (VAS) and neck disability
      index (NDI). The objective measures consisted of neck range of motion (ROM) and
      pain threshold (PT). Both the real and sham treatments significantly reduced
      subjective pain, without significant differences between groups for most
      subjective measures. Objective measures showed no significant change for either
      group before and after each period or by inter-groups analysis. A minimum 16-week
      effect of both real and sham acupuncture was found for subjective measures in the
      follow-up periods. Further study is recommended with an increased sample size, a
      longer washout period, and a longer baseline period.

PMID- 12067087
TI  - The radioprotective effects of bu-zhong-yi-qi-tang: a prescription of traditional
      Chinese medicine.
AB  - We evaluated the effect of bu-zhong-yi-qi-tang, a prescription of traditional
      Oriental medicine, and its major ingredients on protection of the intestine and
      hematopoietic organs against radiation damage in this study. The jejunal crypt
      survival, endogenous spleen colony formation, and apoptosis in jejunal crypt
      cells were investigated in mice irradiated with high and low doses of gamma-rays.
      bu-zhong-yi-qi-tang administration before irradiation protected the jejunal
      crypts (p < 0.0001), increased the formation of the endogenous spleen colony (p <
      0.05) and reduced the frequency of radiation-induced apoptosis (p < 0.05). In
      experiments on the effects of the individual ingredient of bu-zhong-yi-qi-tang,
      Rensan (Radix Ginseng), Danggui (Radix Angelicae gigantis), Shengma (Rhizoma
      Cimicifugae) and Chaihu (Radix Bupleuri) might have major radioprotective
      effects, and each might have different degrees of effect on these three
      endpoints. These results indicated that bu-zhong-yi-qi-tang might be a better
      agent than any one of its ingredients to satisfy all three endpoints. Although
      the mechanisms of this inhibitory effect remain to be elucidated, these results
      indicated that bu-zhong-yi-qi-tang might be a useful radioprotector, especially
      since it is a relatively non-toxic natural product. Further studies are needed to
      better characterize the protective nature of bu-zhong-yi-qi-tang extract and its
      ingredients.

PMID- 12067089
TI  - Computer automated prediction of potential therapeutic and toxicity protein
      targets of bioactive compounds from Chinese medicinal plants.
AB  - Understanding the molecular mechanism and pharmacology of bioactive compounds
      from Chinese medicinal plants (CMP) is important in facilitating scientific
      evaluation of novel therapeutic approaches in traditional Chinese medicine. It is
      also of significance in new drug development based on the mechanism of Chinese
      medicine. A key step towards this task is the determination of the therapeutic
      and toxicity protein targets of CMP compounds. In this work, newly developed
      computer software INVDOCK is used for automated identification of potential
      therapeutic and toxicity targets of several bioactive compounds isolated from
      Chinese medicinal plants. This software searches a protein database to find
      proteins to which a CMP compound can bind or weakly bind. INVDOCK results on
      three CMP compounds (allicin, catechin and camptotecin) show that 60% of computer
      identified potential therapeutic protein targets and 27% of computer-identified
      potential toxicity targets have been implicated or confirmed by experiments. This
      software may potentially be used as a relatively fast-speed and low-cost tool for
      facilitating the study of molecular mechanism and pharmacology of bioactive
      compounds from Chinese medicinal plants and natural products from other sources.

PMID- 12067090
TI  - Rasayanas: evidence for the concept of prevention of diseases.
AB  - Rasayanas are non-toxic Ayurvedic complex herbal preparations or individual herbs
      used to rejuvenate or attain the complete potential of an individual in order to
      prevent diseases and degenerative changes that leads to disease. The present
      paper reviews various activities of rasayanas to support the above concept, its
      role as a prophylactic medication and significance in the prevention of diseases
      in both healthy as well as diseased individuals. The emerging data suggest that
      the possible mechanisms may be by immunostimulation, quenching free radicals,
      enhancing cellular detoxification mechanisms, repair damaged non-proliferating
      cells, inducing cell proliferation and self-renewal of damaged proliferating
      tissues, and replenishing them by eliminating damaged or mutated cells with fresh
      cells.

PMID- 12067091
TI  - Misuse of randomization: a review of Chinese randomized trials of herbal
      medicines for chronic hepatitis B.
AB  - The quality of randomization of Chinese randomized trials on herbal medicines for
      hepatitis B was assessed. Search strategy and inclusion criteria were based on
      the published protocol. One hundred and seventy-six randomized clinical trials
      (RCTs) involving 20,452 patients with chronic hepatitis B virus (HBV) infection
      were identified that tested Chinese medicinal herbs. They were published in 49
      Chinese journals. Only 10% (18/176) of the studies reported the method by which
      they randomized patients. Only two reported allocation concealment and were
      considered as adequate. Twenty percent (30/150) of the studies were imbalanced at
      the 0.05 level of probability for the two treatments and 13.3% (20/150)
      imbalanced at the 0.01 level in the randomization. It is suggested that there may
      exist misunderstanding of the concept and the misuse of randomization based on
      the review.

PMID- 12067092
TI  - A critical analysis of professional and academic publications on traditional
      Chinese medicine in China.
AB  - An open competition for scientific reports on Chinese medicine invited
      enthusiastic subscriptions of over 10,000 manuscripts. Three categories were
      separated viz, clinical studies, literature review and laboratory studies.
      Reports of very high quality were found among the literature review group.
      Clinical studies appeared to be generally weak; very few follow the evidence
      based approach or pass the test of biometa-analysis.

PMID- 12067093
TI  - Magnets on ears helped diabetics.
AB  - Magnets were attached on auricular acupuncture points of diabetes patients. This
      treatment lowered the blood glucose levels and improved eye conditions.

PMID- 12067094
TI  - Hypothalamic effects of millimeter wave irradiation depend on location of exposed
      acupuncture zones in unanesthetized rabbits.
AB  - On nine unanesthetized male rabbits, the frequency spectra of hypothalamic
      electrogram (EEG) were studied during low intensity (10 mW/cm2) millimeter wave
      (55-75 GHz) exposure to various acupuncture points (zone): auricular, cranial and
      corporal. The chances of occurrence of significant (p < 0.05) changes in the EEG
      spectra during irradiation versus, sham experiments were equal to 31, 21 and 5%,
      respectively. Exposure to auricular zone reduced the EEG power in narrow bands
      with central frequencies of 5.3, 15.9 Hz and increased ones of 2.6, 3.2, 6.9,
      7.9, 11.5 and 25.6 Hz. The main effect of exposure to cranial zone was similar-
      changes at 15.9 and 25.6 Hz only. The data obtained demonstrate that the
      responsiveness of the central nervous system to low intensity millimeter wave
      radiation may depend on the location of the exposed acupuncture zone.

PMID- 12067095
TI  - Effectiveness of acupuncture and moxibustion treatment for lymphedema following
      intrapelvic lymph node dissection: a preliminary report.
AB  - Although it is difficult in Western medicine to eliminate edema occurring in the
      lower extremities after intrapelvic lymph node dissection for malignant
      gynecologic tumors, we successfully treated or prevented this postoperative
      complication with moxibustion and acupuncture, initiated after the occurrence of
      lymphedema in 12 patients and as soon as possible after surgery in 12 others. An
      increase in deep body temperature with acupuncture or moxibustion was found to be
      essential for successful treatment.

PMID- 12067096
TI  - Does Deqi (needle sensation) exist?
AB  - The mechanism, by which acupuncture works is not yet clear, therefore there is no
      unequivocal consensus about styles and sensations of needling. To enhance the
      scientific base of acupuncture, needling somehow should be objectified. The term
      Deqi is understood to represent all or at least the main form of phenomena to
      acupuncture stimulation. The characteristics of Deqi, however, have always been
      based on a translation of original Chinese description. Hoping to find a clue to
      develop sham (placebo) method for subject blinding, we investigated which
      sensations are frequently expected and experienced, and whether or not these
      expectations and experiences of sensations are similar in naive subjects. The
      acupuncture sensation scale developed by Vincent et al. (1989) was translated
      into Korean. Thirty-eight healthy acupuncture naive female volunteers (mean age
      29.1, range 25-39) were asked to complete the sensation scale of acupuncture
      according to what they expected needling to feel like before needling. Needling
      was done on left Hegu (LI4) point in the hand and consisted of insertion,
      stimulation for 30 seconds, and removal. Directly after needling, the subjects
      were asked to complete the same sensation scale according to what they
      experienced. The subjects expected to feel hurting, penetrating, sharp, tingling,
      pricking and stinging, and actually experienced aching, spreading, radiating,
      pricking and stinging more than 60% of the time. Comparison between expectation
      and experience, the subjects expected more penetrating, tingling, pricking and
      burning than they experienced, and on the contrary experienced more aching,
      pulling, heavy, dull, electric and throbbing than they expected. Traditionally
      described sensations of Deqi are something beyond just a general pain dimension
      in the Korean population. Further study involving acupuncture experienced
      subjects or subjects from other cultures need to confirm this finding. Moreover,
      sham acupuncture should be studied.

PMID- 12067097
TI  - The effects of long-term herbal treatment for pediatric AIDS.
AB  - This paper presents our long-term (1992-2000) treatment of pediatric Acquired
      Immune Deficiency Syndrome (AIDS) patients (maximum 100 children, last three
      years 65) using native herbal remedies in a voluntary medical assistance program
      in Constanta, Romania. We primarily report the progress of 10 children at a
      facility called the "House of Tomorrow" and three other facilities. The long-term
      (8 years and 8 months) treatment contributed to a drop of the amount of Human
      Immunodeficiency Virus Ribonucleic Acids (HIV-RNA) below the measurable level for
      9 out of 10 patients at the "House of Tomorrow." Furthermore, the treatment led
      to preservation and increase of the cluster of differentiation (CD4) count, a
      remarkable decrease in mortality rate, as well as the maintenance of a good
      quality of life. It took one to three years for the beneficial effects of the
      treatment to emerge. No side-effects were recognized either clinically or
      biochemically, nor was there any emergence of drug-resistant strains of HIV as
      seen with anti-HIV chemical treatments. This paper also refers to which herbal
      remedies were used and their general mechanism of action.

PMID- 12067098
TI  - Effects of Kampo herbal medicine on plasma melatonin concentration in patients.
AB  - There are studies reporting that some natural products containing melatonin.
      Sleep disturbance and nocturnal polyuria are related to abnormal biorhythm. It is
      possible that kampo medicine may influence biorhythm. We therefore examined the
      symptoms and plasma melatonin of patients treated with rokumi-gan, hachimi-jio
      gan, gosha-jinki-gan and seishinrenshi-in. Furthermore, the concentration of four
      kampo medicines and crude drugs making up these formulations were investigated.
      Diurnal plasma melatonin was not affected by Rokumi-gan, but tended to be lowered
      by treatment with hachimi-jio-gan, gosha-jinki-gan and seishinrenshi-in.
      Melatonin was present in several extracts from crude drugs, namely Rehmanniae
      radix, Moutan cortex, Cinnamomi cortex, Aconiti tuber, Plantaginis semen,
      Scutellariae radix and Lycii radicis cortex.

PMID- 12067099
TI  - The effect of whole bee venom on arthritis.
AB  - This study was performed to assess the clincotherapeutic effect of whole venom of
      honeybee (Apis mellifera) in adjuvant-induced arthritic rat. Ninety Sprague
      Dawley male rats were injected with complete Freund's adjuvant (CFA). Adjuvant
      arthritis was produced by a single subcutaneous injection of I mg Mycobacterium
      butyricum suspended in 0.1 ml paraffin oil into the right hind paw. Righting
      reflex was uniformly lost and considered to be the point of arthritis development
      on day 14 after CFA injection. The experiments were divided into three groups.
      When arthritis was developed in the rat, tested groups were administered with
      prednisolone (10 mg/kg, p.o.) or honeybee venom (one bee, s.c.) every other day
      for another 14 days. Control group was injected with 0.1 ml of physiological
      saline solution subcutaneously. Clinical and hematological values with
      histopathological findings were observed during the drug administration. In
      treatment groups, the development of inflammatory edema and polyarthritis was
      suppressed. No significant differences of hind paw edema volume and lameness
      score between prednisolone and honeybee venom groups were observed during
      treatment. White blood cell counts of control group showed leucocytosis that was
      significantly different from the two treatment groups (p < 0.01). Erosions of
      articular cartilage and inflammatory cell infiltrations into interphalangeal
      joint were effectively suppressed in treated groups. In conclusion, whole
      honeybee venom was found to suppress arthritic inflammation in the rat. This may
      be an alternative treatment of arthritic agony in humans.

PMID- 12067100
TI  - Antidiabetic effect of nitobegiku in KK-Ay diabetic mice.
AB  - In the past, nitobegiku (the herb of Tithonia diversifolia (Hemsl) A. Gray) has
      been used as a medicinal plant for diabetes. Antidiabetic effect of the water
      extract of Nitobegiku (NG) was investigated in KK-Ay-mice--one of the animal
      models of type 2 diabetes. NG (1,500 mg/kg body weight) reduced the blood glucose
      of KK-Ay mice from 509 +/- 22 mg/dl to 340 +/- 14 mg/dl (p < 0.001) and also
      lowered the plasma insulin (p < 0.05) 7 hours after single oral administration.
      No change in blood glucose of NG-treated normal mice (ddY) was seen. These
      results support that NG improve glucose metabolism by reducing insulin
      resistance. Therefore, NG may be useful for treatment of type 2 diabetes.

PMID- 12067101
TI  - Anti-hypertensive effect of water extract of danshen on renovascular hypertension
      through inhibition of the renin angiotensin system.
AB  - A study was designed to elucidate the mechanism of anti-hypertensive effects of
      danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive
      model, which is the renin-angiotensin system (RAS)-dependent hypertensive model.
      We investigated the effects of water extracts of danshen on the angiotensin
      converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone
      levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of
      danshen extract in a dose-dependent manner. SBP was decreased significantly after
      administration of danshen extract in 2K1C, whereas plasma renin activity (PRA)
      was not changed. The plasma concentration of aldosterone (PAC) was decreased
      significantly in 2K1C group administered with Danshen extract, whereas the plasma
      concentration of ANP was increased by administration of danshen extract for three
      weeks. These results suggest that danshen has an anti-hypertensive effect through
      the inhibition of ACE, an essential regulatory enzyme of RAS.

PMID- 12067102
TI  - Inhibitory effect of Carthamus tinctorius L. seed extracts on bone resorption
      mediated by tyrosine kinase, COX-2 (cyclooxygenase) and PG (prostaglandin) E2.
AB  - Anti-bone resorption properties of the Korean herbal formulation, Honghwain (HHI;
      Carthamus tinctorius L. seed) was biochemically investigated. On processing bone
      metabolism, PGE2 accelerated production of IL-1beta in fetal mouse osteoblast and
      stimulated physiological activation substance, IL-1beta. The novel class of Src
      tyrosine kinase inhibitors, Herbimycin A (HERB) and HHI reduced COX-2 mRNA levels
      as well as PGE2 production induced by IL-1beta, TNF-alpha and IL-6. HHI inhibited
      in vitro and in vivo bone resorption by inhibition of phosphorylation of peptide
      substrates. HHI dose-dependently reduced the hypercalcemia induced in mice by IL
      1beta and partly prevented bone loss and microarchitectural changes in young
      ovariectomized rats, showing that the protective effect on bone was exerted via
      the inhibition of bone resorption. These results indicate that the synergy
      between IL-beta, TNF-alpha, IL-6 on PGE2 production is due to an enhanced gene
      expression of COX-2 and that tyrosine kinase (s) are involved in the signal
      transduction of COX-2 in mouse calvarial osteoblasts. Thus, HHI as a possible Src
      family kinase inhibitor may be useful for the treatment of diseases associated
      with elevated bone loss.

PMID- 12067103
TI  - Incidence and patterns of spinal cord injury in Australia.
AB  - The objective of this paper is to report on the epidemiology of spinal cord
      injury (SCI) based on the Australian SCI register and to discuss the implications
      for prevention. All adult cases of SCI are reported to the registry. The case
      reports for 1998/1999 were aggregated and described. The age adjusted rate of
      persisting SCI was 14.5 per million of population. Rates were highest in young
      adults and in males. The vast majority of cases (93%) were due to unintentional
      injury. Forty-three percent were due to motor vehicle crashes, principally from
      motor vehicle rollover. Cases of SCI from falls, aquatic activities, and working
      for income are also described. Incomplete cervical cord injuries were most common
      (38%), particularly as a result of motor vehicle crashes and low falls. The study
      indicates that the surveillance of SCI needs to be improved internationally so
      that comparative studies can be undertaken. It is recommended that the Centers
      for Disease Control case definition be adopted. Australia is one of the few
      countries that have a register based on that case definition, and the only one
      that has a register covering a full national adult population. The results
      presented on the basis of this data source provide some hitherto unavailable
      information on the incidence rates and patterns of SCI. National population based
      surveillance is fundamental to an understanding of the epidemiology, and hence
      the prevention, of this severe and costly health and welfare problem.

PMID- 12067104
TI  - Generalised linear accident models and goodness of fit testing.
AB  - This paper has two aims. The primary aim is to provide a practical resolution of
      the low mean value' problem, a barrier to goodness of fit testing for the
      commonly used generalised linear accident model. A secondary aim of the paper is
      to describe the underlying mechanism of these models, so making them fully
      accessible to the transport modeller.

PMID- 12067105
TI  - Drinking and driving among Mexican American and non-Hispanic white males in Long
      Beach, California.
AB  - Although drinking and driving in the United States has declined substantially
      during the past two decades, this trend has not been seen among Hispanic drivers.
      Higher rates of driving while impaired (DWI) arrests and alcohol-related crashes,
      particularly among Mexican Americans, also have been noted. The extent to which
      this reflects a lack of understanding of DWI laws rather than a disregard for
      them is unknown. A survey was conducted among Mexican American and non-Hispanic
      white male DWI arrestees in Long Beach, California, to ascertain alcohol use,
      attitudes toward drinking and drinking and driving, and knowledge of DWI laws.
      The findings were compared with those of Mexican American and non-Hispanic white
      males recruited from the local community. Mexican American males, both DWIs and
      those from the community, reported heavier drinking than non-Hispanic white
      males. All four groups of respondents tended to underestimate the number of
      drinks needed to achieve the blood alcohol concentration (BAC) threshold at or
      above which it is illegal to drive under California law. Estimations were around
      2-3 drinks rather than a more realistic estimate of 4-5 drinks. However, Mexican
      American DWIs and their comparison group vastly overestimated the number of
      drinks to make them unsafe drivers (8- 10 drinks). Furthermore, fewer than half
      were aware of the BAC threshold in California (0.08%) compared with between 60
      and 78% of non-Hispanic whites. This study is limited in scope and needs to be
      replicated in other communities and with other racial/ethnic groups. However, the
      clear lack of knowledge of the DWI law in California and a lack of understanding
      of the relationship between number of drinks and BAC point to the need for
      culturally sensitive programs that are developed and implemented within the
      Mexican American community.

PMID- 12067106
TI  - A study to measure the incidence of driving under suspension in the Greater
      Moncton area.
AB  - Roadside checkpoints were used to determine the percentage of motorists driving
      while suspended (DWS) during various times of the day. These data showed that the
      percentage of motorists DWS was 57% of the expected value relative to their
      representation among all drivers. Data also showed that suspended drivers make up
      a higher percentage of drivers on the road after midnight. Results also indicated
      that 90% of suspended drivers stopped in this study produced a driving permit
      even though they are required to surrender it when suspended. In order to compare
      data collected at roadside checkpoints with self-report data. a questionnaire was
      administered to 456 persons taking a re-education course for first offenders and
      68 participants taking a re-education course for second offenders. The results
      indicated that participants under-represented their own incidence of DWS.
      However, when asked about the driving behavior of other suspended drivers, their
      estimates were much closer to the data obtained with the roadside survey.

PMID- 12067107
TI  - Evaluation of a program to motivate impaired driving offenders to install
      ignition interlocks.
AB  - Approximately 30,000 alcohol ignition interlocks, which are designed to prevent
      the operation of a vehicle if the driver has been drinking, are in use in the US
      and Canada. Ignition interlock programs are also being initiated in Sweden and
      Australia. The best-controlled studies that are currently available suggest that
      ignition interlocks are effective in reducing impaired driving recidivism while
      on the vehicle. However, in the US, the practical effectiveness of these devices
      is limited because only a small number of offenders are willing to install them
      in order to drive legally. This paper reports on a study of a court policy that
      created a strong incentive for impaired driving offenders to install interlocks
      by making traditional penalties, such as jail or electronically monitored house
      arrest, the alternative to participation in an interlock program. Comparison of
      the recidivism rates of offenders subject to this policy with offenders in
      similar, nearby courts, not using interlocks, indicated that the policy was
      producing substantial reductions in DUI recidivism.

PMID- 12067108
TI  - Pedestrian risk decrease with pedestrian flow. A case study based on data from
      signalized intersections in Hamilton, Ontario.
AB  - A unique database provided information on pedestrian accidents, intersection
      geometry and estimates of pedestrian and vehicle flows for the years 1983-1986
      for approximately 300 signalized intersections in Hamilton, Ont., Canada.
      Pedestrian safety at semi-protected schemes, where left-turning vehicles face no
      opposing traffic but have potential conflicts with pedestrians, were compared
      with pedestrian safety at normal non-channelized signalized approaches, where
      right-turning vehicles have potential conflicts with pedestrians. Four different
      ways of estimating hourly flows for left- and right-turning vehicles were
      explored. Hourly flows were estimated for periods of 15 min, hours, two periods a
      day (a.m. and p.m.) and the 'daily' period (7 h). Parameter estimates were
      somewhat affected by the time period used for flow estimation. However, parameter
      estimates seem to be affected far more by the traffic pattern (left- or right
      turning traffic), even though approaches were selected such that the situation
      for left- and right-turning turning traffic was similar (no opposing traffic, no
      advanced green or other separate phases and no channelization). Left-turning
      vehicles caused higher risks for pedestrians than right-turning vehicles. At low
      vehicular flows right turns and semi-protected left turns seemed to be equally
      safe for pedestrians. When risks for pedestrians were calculated as the expected
      number of reported pedestrian accidents per pedestrian, risk decreased with
      increasing pedestrian flows and increased with increasing vehicle flow. As risk
      decreases with increasing pedestrian flows, promoting walking will have a
      positive effect on pedestrian risk at signalized intersections.

PMID- 12067109
TI  - Road traffic accidents in the United Arab Emirates: trends of morbidity and
      mortality during 1977-1998.
AB  - High rates of serious road traffic accidents (RTAs) have been reported for
      several Arabian Gulf countries, including the United Arab Emirates (UAE). in
      recent years. This study aims to describe quantitatively the morbidity and
      mortality from RTAs in the UAE, to identify their trends during the period 1977
      1998, to compare the results with those of developed countries, and to evaluate
      the information available on possible causes with a view to identifying the most
      useful direction for future research. Data were obtained from UAE's police and
      health sources and, for international comparison, from WHO Statistics reports and
      the published literature. Overall and cause-specific fatality and injury rates of
      RTAs were calculated. Estimates of trends were achieved by using linear
      regression. The characteristics of road users injured or killed were also
      analysed. The results revealed that during the period 1977-1998, the rates of
      RTAs per 100,000 population and per 100,000 motor vehicles declined in the UAE by
      a trend component of -56.3 (P < 0.001: R2 = 0.69) and -521.8 (P<0.001; R2=0.92),
      respectively. RTA fatality and injury rates based on the same denominators also
      declined by -1.1 (P<0.001; R2 = 0.56) and -13.3 (P < 0.001; R2 = 0.47); and by 
      3.8 (P < 0.02; R2 = 0.23) and - 90.0 (P < 0.001; R2 = 0.59), respectively.
      Paradoxically, however, except for a short period (1977-1985), a steady increase
      in the risk of injury and death in each RTA accompanied these declines. Between
      1985 and 1998 the severity rate (the ratio of fatalities and injuries per 1,000
      RTAs) more than tripled in the UAE. The UAE's rates were high when compared with
      a number of selected countries. The cause for the increasing severity of RTAs is
      not clear but the most likely cause could lie in speeding, careless driving, the
      changing vehicle mix on the roads and the standard of immediate care available
      for victims. Further investigation is essential and will require close
      collaboration between police and health authorities.

PMID- 12067110
TI  - Injury to the spinal cord in motor vehicle traffic crashes.
AB  - Motor vehicle traffic crashes (MVTCs) are the leading cause of traumatic spinal
      cord injury. Evidence of putative risk factors for this type of injury comes
      largely from descriptive studies. This study is the first case-control study of
      risk factors for spinal cord injury specifically in car crashes. Cases of
      occupant spinal cord injury in South Australia were identified from the
      Australian Spinal Cord Injury Register (ASCIR) which provides full coverage of
      the adult population. The comparison group was other seriously injured car
      occupants. In single vehicle car crashes in the country, the likelihood of spinal
      cord injury was five times higher for occupants of non-sedan type cars compared
      with sedans. The likelihood of spinal cord injury was especially high in non
      sedan type cars involved in rollover crashes; ten times higher than sedans. The
      implications of the findings for prevention are highlighted. Concern is expressed
      over the increasing proportion of four wheel drive passenger vehicles (sport
      utility vehicles) in the car fleet in Australia, and in the USA, as they are more
      prone to rollover.

PMID- 12067111
TI  - The role of ambient light level in fatal crashes: inferences from daylight saving
      time transitions.
AB  - The purpose of this study was to estimate the size of the influence of ambient
      light level on fatal pedestrian and vehicle crashes in three scenarios. The
      scenarios were: fatal pedestrian crashes at intersections, fatal pedestrian
      crashes on dark rural roads, and fatal single-vehicle run-off-road crashes on
      dark, curved roads. Each scenario's sensitivity to light level was evaluated by
      comparing the number of fatal crashes across changes to and from daylight saving
      time, within daily time periods in which an abrupt change in light level occurs
      relative to official clock time. The analyses included 11 years of fatal crashes
      in the United States, between 1987 and 1997. Scenarios involving pedestrians were
      most sensitive to light level, in some cases showing up to seven times more risk
      at night over daytime. In contrast, single-vehicle run-off-road crashes showed
      little difference between light and dark time periods, suggesting factors other
      than light level play the dominant role in these crashes. These results are
      discussed in the context of the possible safety improvements offered by new
      developments in adaptive vehicle headlighting.

PMID- 12067112
TI  - Emergency medical service rescue times in Riyadh.
AB  - The emergency medical service (EMS) in Saudi Arabia is managed by each hospital
      through the Saudi Red Crescent Society (SRCS). There are approximately 165
      ambulance stations in the country, each with two ambulances. The SRCS collects
      data on EMS requests and ambulance arrival times at the accident scene. Each
      emergency incident has its own implications (accident, fire, injury, etc.) and
      must be dealt with individually. The aims of this study are to evaluate ambulance
      rescue time, which includes response time, in the city of Riyadh, the capital of
      Saudi Arabia; to analyze this time for road traffic accidents; and to compare the
      response time in Riyadh with corresponding times in other countries. A sample of
      874 emergency calls was collected during 1999. Ambulance rescue time consists of
      three components: response time, time at the scene and travel time to the
      hospital. Data analysis showed that rescue time is, on average, 35.84 min (S.D. =
      6.43 min). Within this time, the average response time is 10.23 min (S.D. = 5.66
      min). Other service components (e.g. ambulance time at the accident scene and
      travel time to the hospital) are analyzed and detailed statistics are given.
      Ambulance speed to the accident averages approximately 55.05 km/h (S.D. = 27.42
      km/h). One primary finding is that there is room for improvement in the rescue
      time in Riyadh, which would save more lives, through an increase in the
      efficiency of ambulance team performance. A test statistic is developed in this
      study to carry out a simple hypothesis testing for percentiles. This test
      statistic, which is generic and can be used for other applications, is used to
      compare EMS response time in Riyadh with that in other parts of the world.

PMID- 12067113
TI  - Predicted effect of automatic crash notification on traffic mortality.
AB  - OBJECTIVE: To estimate the reduction in traffic mortality in the United States
      that would result from an automatic crash notification (ACN) system. METHODS:
      1997 Fatality Analysis Reporting System (FARS) data from 30,875 cases of
      incapacitating or fatal injury with complete information on emergency medical
      services (EMS) notification and arrival times were analyzed considering cases at
      any time to be in one of four states: (1) alive prior to notification; (2) alive
      after notification; (3) alive after EMS arrival; and (4) dead. For each minute
      after the crash, transition probabilities were calculated for each possible
      change of state. These data were used to construct models with (1) number of
      incapacitating injuries ranging from FARS cases up to an estimated total for the
      US in 1997; (2) deaths equal to FARS total; (3) transitions to death from other
      states proportional to FARS totals and rates and (4) other state transitions
      equal to FARS rates. The outcomes from these models were compared to outcomes
      from otherwise identical models in which all notification times were set to 1
      min. RESULTS: FARS data estimated 12,823 deaths prior to notification, 1800 after
      notification, and 14,015 between EMS arrival and 6 h. If notification times were
      all set to 1 min, a model using FARS data only predicted 10,703 deaths prior to
      notification, 2,306 after notification, and 15,208 after EMS arrival, while a
      model using an estimated total number of incapacitating injuries for the US
      predicted 9,569 deaths prior to notification, 2,261 after notification, and
      15,134 after arrival. In the first model, overall mortality was reduced from
      28,638 to 28,217 (421 per year. or 1.5%), while in the second model mortality was
      reduced to 26,964 (1,674 per year, or 6%). CONCLUSIONS: Modest but important
      reduction in traffic mortality should be expected from a fully functional ACN
      system. Imperfect systems would be less effective.

PMID- 12067114
TI  - Modeling young driver motor vehicle crashes: data with extra zeros.
AB  - Much of the data collected on motor vehicle crashes is count data. The standard
      Poisson regression approach used to model this type of data does not take into
      account the fact there are few crash events and hence, many observed zeros. In
      this paper, we applied the zero-inflated Poisson (ZIP) model (which adjusts for
      the many observed zeros) and the negative binomial (NB) model to analyze young
      driver motor vehicle crashes. The results of the ZIP regression model are
      comparable to those from fitting a NB regression model for general over
      dispersion. The findings highlight that driver confidence/adventurousness and the
      frequency of driving prior to licensing are significant predictors of crash
      outcome in the first 12 months of driving. We encourage researchers, when
      analyzing motor vehicle crash data, to consider the empirical frequency
      distribution first and to apply the ZIP and NB models in the presence of extra
      zeros due, for example, to under-reporting.

PMID- 12067115
TI  - Seat belt use among African Americans, Hispanics, and Whites.
AB  - OBJECTIVES: This study investigated seat belt use among White, Black, and
      Hispanic drivers, in cities in which standard enforcement of the belt use law is
      permitted (primary enforcement) and in cities in which a motorist has to be first
      cited for another offense (secondary enforcement). Socioeconomic and gender
      differences in belt use were also studied. METHODS: Belt use observations were
      obtained at gas stations in Boston, Chicago, Houston, and New York City. In short
      interviews with drivers, information on race/ethnicity and education was
      obtained. RESULTS: Belt use was higher in primary enforcement cities, among
      women, and among those with at least a college degree. In primary law cities
      there were no clear differences in belt use by race/ethnicity; in secondary
      cities African Americans were less likely than Whites or Hispanics to be belted,
      among populations both with and without college degrees. This is consistent with
      data from other studies indicating that African Americans are more sensitive than
      Whites to the enforcement of primary laws and are more likely to increase belt
      use when states shift from secondary to primary. There has been no evidence of
      enforcement bias against African Americans--increases in citations generally have
      been greater among Whites than African Americans once primary enforcement is
      implemented. CONCLUSIONS: More widespread application of primary laws--standard
      throughout the world but in only 17 US states and the District of Columbia--would
      increase belt use for all drivers, especially African Americans.

PMID- 12067116
TI  - Derivation of a clinical decision rule for whiplash associated disorders among
      individuals involved in rear-end collisions.
AB  - A prospective study was used to: (1) quantify potential risk factors for whiplash
      associated disorder following a rear-end motor vehicle collision; and (2) develop
      a simple clinical decision rule for the early identification of patients at risk
      for long-term whiplash associated disorder. Between 1 October 1995 and 31 March
      1998, 446 adults involved in rear-end collisions presented to the only two
      emergency departments serving Kingston, Ontario. Eligible and consenting subjects
      (n = 353) were contacted by telephone soon after the collisions then at multiple
      occasions up to 2 years post-collision. Bivariate and multiple logistic
      regression analyses were used to identify potential risk factors for persistent
      symptoms. A software package that uses Chi-squared automatic interaction
      detection and classification and regression trees was used to develop a simple
      clinical decision rule for the identification of patients at high and low risk
      for persistent whiplash associated disorder. Risk factors identified by
      regression analyses included: increased age, number of initial physical symptoms,
      and early development of the following symptoms: upper back pain, upper extremity
      numbness or weakness, or disturbances in vision. A simple clinical decision rule
      that requires asking up to three basic questions of each patient was derived and
      would have identified the 118 cases of persistent whiplash associated disorder
      with a sensitivity of 91.5% (95% confidence interval: 86.5, 96.6) and a
      specificity of 51.4% (44.7, 58.1). This study confirmed the importance of several
      risk factors for whiplash associated disorder following rear-end motor vehicle
      collisions.

PMID- 12067117
TI  - Differences in cause-specific patterns of unintentional injury mortality among 15
      44-year-olds in income-based country groups.
AB  - OBJECTIVES: The aim of the present study was to investigate the cause-specific
      patterns of unintentional injury mortality among 15-44-year-olds in various
      income-based country groups, and to analyze which specific causes contribute the
      most to the unintentional injury mortality in each country group. MATERIALS AND
      METHODS: Cross-sectional data on the five most common causes of unintentional
      injury mortality by age-sex specific subgroups were compiled for 57 countries
      from the World Health Statistics Annuals for the year 1993 (1991-1994 if
      information for 1993 was unavailable). Data were categorized into four income
      based country groups according to their gross national product (GNP) per capita
      for the year 1993. The differences between means and rate ratios of low, lower
      middle, and upper-middle income countries were calculated by comparing them with
      those of the high-income countries. Regression analysis was performed to
      determine the trends in the direction of income for each specific cause of
      unintentional injury mortality by age-sex. RESULTS: For any of the specific
      causes of unintentional injury mortality there was an inverse relationship
      between mortality rates and GNP per capita except for motor vehicle traffic (MVT)
      among the 15-24-year-old age group. MVT accidents were the most common cause and
      contributed 26-77% of all unintentional injury mortality. The second most common
      cause was poisoning in all country groups except low-income countries where
      drowning dominated for males and mixed causes for females. Upper-middle income
      countries represented the highest MVT mortality in all age-sex subgroups except
      among 15-24-year-old females for which high-income countries displayed the
      highest rate. For other causes, lower-middle income represented the highest rates
      with a few exceptions. In the 15-24-year age group, the rate ratio of motor
      vehicle traffic mortality was higher in high-income countries compared to low
      income countries, while in the 35-44-year age group, all other country groups
      showed a higher rate ratio than high-income countries. Drowning for males and
      burns for females in the low and middle-income countries were significantly
      higher than in high-income countries.

PMID- 12067118
TI  - Perceived risk among parents concerning the travel situation for children with
      disabilities.
AB  - The aim of this study was to describe perceived risk among parents concerning the
      travel situation for children with disabilities, in addition to their self
      reported knowledge of regulations and standards. The results from the present
      questionnaire study showed that entering and exiting the vehicles often required
      manual assistance and, thus, was perceived as risky, creating worry among
      parents. Parents were also worried about professional drivers' lack of knowledge
      about the child, incautious driving behaviour and lack of adequate safety
      measures. A poor postural sitting position was a problem in all vehicles. Half of
      the parents lacked knowledge about the regulations and standards for school
      transportation and Special Transport Systems. Lack of information seems to be one
      underlying reason for the parents' worries. Comprehensive information, focused on
      the special needs of children with disabilities in their transportation, would
      probably reduce the parents' worries significantly.

PMID- 12067119
TI  - Snowmobile fatalities aspects on preventive measures from a 25-year review.
AB  - During October 1973 through May 1998, 157 snowmobile fatalities were autopsied in
      Northern Sweden, including 131 riders, 15 passengers, six occupants with unknown
      position and five victims pulled by a snowmobile. Most fatalities occurred during
      March and April (41%), on weekends/holidays (75%), between 18:00 and 02:00 h
      (59%), during darkness (63%), in clear weather (84%) and at leisure time (94%).
      The median age was 39 years and 92% were men. The most common causes of death
      were blunt trauma (53%) and drowning (38%). A total of 64% were inebriated by
      alcohol, with a mean blood alcohol concentration of 1.7 g/l. More inebriated
      victims were found during weekends/holidays than on weekdays (75 vs. 51%) and
      during nighttime than during daytime (92 vs. 52). Driving into water was the most
      common event (38%) followed by collisions with immobile objects (20%). Alcohol
      and speeding were the most common contributors to the crashes, while flotation
      snowmobile suit and helmet use were considered to be the most important injury
      prevention factors.

PMID- 12067120
TI  - A comparative study of apical leakage of Endomethasone, Top Seal, and Roeko Seal
      sealer cements.
AB  - A comparison was made of the apical leakage of three sealers. Fifty single-root
      human teeth were randomly divided into 5 groups (n = 10; 3 experimental and 2
      control). The teeth of the positive-control and experimental groups were
      instrumented with K-type files to size 45. The experimental groups were obturated
      by laterally-vertically, condensed gutta-percha with Endomethasone, Top Seal, or
      RSA sealer cements. The positive-control group was nonobturated and the negative
      control group was noninstrumented. The root surfaces were then coated with nail
      varnish (except the apex in the experimental groups) and immersed in black ink
      (for 1 week at 37 degrees C). The statistical evaluation of the results obtained
      by clearing and cross-section techniques showed no significant differences
      between sealers. Leakage, as determined by the clearing technique, was
      significantly greater than that quantified by cross-section analysis.

PMID- 12067122
TI  - Apical leakage of five root canal sealers after one year of storage.
AB  - A fluid transport model study was used to compare the sealing ability of five
      root canal sealers (AH26, AH Plus, Apexit, Diaket, and Ketac-Endo) on 60 single
      rooted teeth after 1 yr of storage. The root canals were prepared with Gates
      Glidden drills by using a step-back technique before lateral condensation of
      gutta-percha with the tested sealers. The specimens were stored in saline
      solution for 1 yr at 37 degrees C. The leakage was measured by the movement of an
      air bubble in a capillary glass tube connected to the experimental root section.
      Apexit (0.490 microl) leaked significantly more than AH Plus (0.378 microl) and
      Ketac-Endo (0.357 microl), whereas AH26 (0.390 microl) and Diaket (0.429 microl)
      showed no significant difference from either Apexit or from AH Plus and Keto
      Endo.

PMID- 12067121
TI  - In situ antimicrobial effectiveness of chlorhexidine and calcium hydroxide: gel
      and paste versus gutta-percha points.
AB  - The aim of this study was to determine the antibacterial effectiveness of either
      chlorhexidine or calcium hydroxide integrated in gutta-percha points compared
      with chlorhexidine or calcium hydroxide delivered as gel or paste, respectively.
      A total of 70 initially sterile roots with open accesses were carried for 1 week
      in the oral cavities of two volunteers. The roots were then removed, and samples
      were taken from the root canals for microbial analysis. The roots were medicated
      with calcium hydroxide paste, 5% chlorhexidine gel, or a chlorhexidine- or
      calcium hydroxide-containing gutta-percha point. The accesses were closed with
      bonding material, and the roots incubated for 1 week. After removal of the
      antimicrobial agents, roots were again checked for bacterial growth. One
      thioglycolate-soaked paper point was then introduced into each canal, and roots
      were incubated for 1 week more to observe bacterial regrowth. After 1 week of
      medication, the absolute bacterial count revealed significant differences
      compared with the controls. However, only the chlorhexidine-gel and the calcium
      hydroxide paste group showed no microbial colonization in a considerable number
      of samples after 1 and 2 weeks.

PMID- 12067123
TI  - Scanning electron microscopy study of the adhesion of Prevotella nigrescens to
      the dentin of prepared root canals.
AB  - The purpose of this study was to evaluate the effect of the presence or absence
      of amorphous, irregular smear layers on the adhesion of Prevotella nigrescens, to
      the dentin of the root canal by using scanning electron microscopy (SEM). Human
      incisors extracted within 7 days, with no cavities, no fractures, and no evidence
      of calcification of the canal, were selected. After cutting the crown portion at
      the CEJ, root canal preparation was undertaken by using a modified crown-down
      technique with Profile and Gates Glidden drills. Ten milliliters of physiologic
      saline solution (groups 1 and 4), 10 ml of 3.5% NaOCl (groups 2 and 5), or 10 ml
      of NaOCl and 10 ml of 0.5 M EDTA (groups 3 and 6) were used as irrigation
      solution while preparing the canal. After vertical sectioning and ethylene oxide
      gas sterilization, samples (groups 1, 2, and 3) were immersed in brain-heart
      infusion broth with yeast extract, hemin, and menadione, inoculated with P.
      nigrescens (ATCC 33563), and incubated for 3 h at 37 degrees C. All samples were
      prepared for and observed with SEM. The data were analyzed by using t test and
      one-way ANOVA. Smear layer was observed to cover the entire root canal surface
      after root canal preparation. Smear layer was removed and the entrances of
      dentinal tubules opened widely after applying 3.5% NaOCl and 0.5 M EDTA. A
      significantly greater number of bacteria were found to adhere to those teeth in
      which a smear layer was present (p < 0.05). Given that the smear layer produced
      during root canal preparation promoted adhesion and colonization of P. nigrescens
      to the dentin matrix, it might also increase the likelihood of canal reinfection.

PMID- 12067124
TI  - Effect of early coronal flaring on working length change in curved canals using
      rotary nickel-titanium versus stainless steel instruments.
AB  - This in vitro investigation examined pre- and postinstrumentation working length
      (WL) measurements in curved root canals. The conditions compared were
      combinations of (a) stainless steel hand files + Gates Glidden drills (SS) versus
      nickel-titanium rotary files (Ni-Ti); and (b) early coronal flaring (flaring
      completed before WL determination) versus late coronal flaring (flaring completed
      after WL determination). Coronal flaring was accomplished for the SS group using
      Gates Glidden drills and for the Ni-Ti group using rotary Ni-Ti files (n =
      15/group). WL was determined before coronal flaring, immediately after coronal
      flaring, and again after canal preparation. Results indicated that WL decreased
      for all canals as a result of canal preparation. The mean decrease in WL was
      significantly greater for the SS group (-0.48 mm +/- 0.32) than for the Ni-Ti
      group (-0.22 mm +/- 0.26). Less change in WL occurred in both groups when initial
      WL was determined after coronal flaring (SS: -0.12 mm +/- 0.13, Ni-Ti: -0.14 mm
      +/- 0.25).

PMID- 12067125
TI  - Intracoronal sealing ability of two dental cements.
AB  - The purpose of this study was to compare the efficacy of sealing the coronal 2-mm
      of the root canals versus covering the entire pulpal floor with one of two dental
      resin cements (Principle or C&B Metabond). Sixty-two molars with the occlusal
      half of the crowns and the apical half of the roots removed were used. Each canal
      was enlarged by using a #3 Gates Glidden bur and obturated with unsealed gutta
      percha cones. The teeth were randomly assigned to four groups, each containing 15
      teeth, plus a negative and a positive control. In group 1, 2 mm of Principle were
      placed over the entire pulpal floor. In group 2, Principle was placed 2 mm into
      each canal orifice. Groups 3 and 4 were the same as groups 1 and 2, except C&B
      Metabond cement was used. After the cement set, the gutta-percha was removed and
      the integrity of the seal was tested by fluid filtration at a pressure of 20 cm
      H2O at 1 h and at 1, 2, and 4 weeks. The data were analyzed by a three-way ANOVA
      and the Student-Newman-Keuls tests at alpha = 0.05. The controls behaved as
      expected. Results showed that there were no statistically significant differences
      among the materials used or the location (p > 0.05), but there was a significant
      difference with respect to time. Principle leaked significantly more than C&B
      Metabond at 1 h (p < 0.05), but the seal became tighter over time. C&B Metabond
      leaked less early (p < 0.05) but increased in leakage at 4 weeks. Both materials
      sealed well over the 4-week study. Principle was easier to use, and sealing the
      entire pulpal floor was easier than sealing only the canal orifice.

PMID- 12067126
TI  - Cyclic fatigue of endodontic nickel titanium rotary instruments: static and
      dynamic tests.
AB  - Endodontic instruments upon rotation are subjected to both tensile and
      compressive stress in curved canals. This stress is localized at the point of
      curvature. The purpose of this study was to evaluate the cyclic fatigue of 0.04
      ProFile nickel titanium rotary instruments operating at different rotational
      speeds and varied distances of pecking motion in metal blocks that simulated
      curved canals. A total of 150 ProFile instruments were made to rotate freely in
      sloped metal blocks at speeds of 200, 300, or 400 rpm by a contra-angle handpiece
      mounted on an Instron machine. The electric motor and Instron machine were
      activated until the instruments were broken in two different modes, static and
      dynamic pecking-motion. The fractured surfaces of separated instruments were
      examined under a scanning electron microscope. All data obtained were analyzed by
      a stepwise multiple regression method using a 95% confidence interval. The
      results demonstrated that the time to failure significantly decreased as the
      angles of curvature or the rotational speeds increased. However, as pecking
      distances increased, the time to failure increased. This is because a longer
      pecking distance gives the instrument a longer time interval before it once again
      passes through the highest stress area. Microscopic evaluation indicated that
      ductile fracture was the major cyclic failure mode. To prevent breakage of a NiTi
      rotary instrument, appropriate rotational speeds and continuous pecking motion in
      the root canals are recommended.

PMID- 12067127
TI  - Detection rate of root canal orifices with a microscope.
AB  - The purpose of this study was to compare the detection rate of root canal
      orifices by three different methods: naked eye, with surgical loupes, and under a
      microscope. Two undergraduate dental students located the orifices of 260 teeth
      by using the above-mentioned methods. Then, India ink was injected into the pulp
      chamber and all teeth were cleared to determine the actual number of the
      orifices. There was a significant difference in the detection rate among the
      three methods (p < 0.01, chi-square test); the microscopic method could more
      accurately detect orifices than the others could. Surgical loupes were relatively
      ineffective compared with the microscopic method for detecting orifices.

PMID- 12067128
TI  - Gutta-percha retreatment: effectiveness of nickel-titanium rotary instruments
      versus stainless steel hand files.
AB  - This study compared the cleanliness of the root canal walls after retreatment
      using nickel titanium (NiTi) rotary and stainless steel (SS) files. Also compared
      were time of retreatment and canal deviation. Forty extracted canines were step
      back prepared and obturated with gutta-percha and sealer. Retreatment was
      performed either by using chloroform and SS hand files or chloroform and NiTi
      rotary files. Time for retreatment was recorded. Radiographs of the root canal
      system before and after retreatment were made. Teeth were split longitudinally,
      photographed, and projected onto a screen. The amount of gutta-percha/sealer
      remaining on the canal walls was then traced and measured. The amount remaining
      was analyzed and compared statistically between NiTi and SS groups by t test.
      Results showed that the mean percentage of wall coverage by remaining obturating
      material in the SS group was 13.6% and was 15.2% for the NiTi group. There was no
      statistically significant difference (p = 0.361). No severe canal deviation
      occurred with either retreatment method. Mean retreatment time for the SS group
      was 6.3 min and 7.9 min for the NiTi group; the difference was statistically
      significant (t test p < 0.001). In conclusion, NiTi rotary and SS hand were
      similar in material remaining after retreatment, but SS hand was a bit faster.

PMID- 12067129
TI  - Incidence of postoperative pain after intracanal procedures based on an
      antimicrobial strategy.
AB  - The purpose of this prospective study was to evaluate the incidence of
      postoperative pain after intracanal procedures based on an antimicrobial
      strategy. Data were examined from 627 teeth that had necrotic pulps or required
      retreatment. Information was obtained for each patient treated with regard to
      presence of preoperative pain. Occurrence of periradicular bone destruction
      detected by radiographs was also recorded. The operators consisted of
      undergraduate students, who were in their first year of clinical training. Root
      canals were instrumented and then medicated with a calcium hydroxide/camphorated
      paramonochlorophenol paste. No systemic medication was prescribed. Approximately
      1 week after the initial appointment, patients were asked about the occurrence of
      postoperative pain and the level of discomfort was rated as no pain, mild pain,
      moderate pain, or severe pain. Data were statistically analyzed using the Chi
      square test. Mild pain occurred in 10% of the cases, moderate in 3.3%, and severe
      (flare-up) in 1.9%. Postoperative pain was significantly associated with the
      treatment of previously symptomatic teeth without periradicular lesions (p <
      0.01). No other correlations were detected between the occurrence of
      postoperative discomfort and other clinical conditions. There was also no
      difference regarding the incidence of postoperative pain between treatment and
      retreatment (p > 0.01). The intracanal procedures used in this study to control
      root canal infections showed a small incidence of postoperative pain,
      particularly flare-ups, even performed by inexperienced undergraduate dental
      students.

PMID- 12067130
TI  - In vitro measurement accuracy of an electronic apex locator in teeth with
      simulated apical root resorption.
AB  - The purpose of this in vitro study was to evaluate the accuracy of Root ZX apex
      locator to determine the working length in teeth with simulated apical root
      resorption. Fifty extracted, single-rooted, human teeth with mature apices were
      used in this study. An irregular cavity defect was drilled at the apex of each
      tooth simulating an apical root resorption. Three operators used the Root ZX to
      measure the working lengths, comparing the electronic readings with the direct
      visual measurements. The Root ZX was 62.7%, 94.0%, and 100.0% accurate to within
      0.5 mm, 1 mm, and 1.5 mm of the direct visual measurements, respectively.
      Statistically significant differences were observed between operator A and B and
      A and C (p < 0.01), but no significant differences were detected between operator
      B and C (p > 0.01).

PMID- 12067131
TI  - Sealer distribution in coronal dentin.
AB  - A major cause of tooth discoloration is sealer remnants in the pulp chamber after
      root canal treatment. The purpose of this study was to assess coronal
      distribution and color changes of four commonly used sealers placed in the pulp
      chamber after 2 yr. Fifty extracted premolars were cross-sectioned in the coronal
      third of the root. The chamber contents were removed, and instrumentation was via
      the canal; then freshly mixed sealer was placed in each chamber. Sealers
      evaluated were: AH 26, Kerr Pulp Canal Sealer, Roth 801, and Sealapex. The apical
      access was sealed with white sticky wax, and the tooth was maintained in a moist
      environment at 37 degrees C for 2 yr. Teeth were split longitudinally, and
      digital images of the exposed dentin were made, scrambled, and evaluated blindly
      by trained evaluators for color changes and for presence of sealer in dentin.
      There was no measurable penetration of sealer into dentin for all groups and no
      dentin discoloration occurred. The sealers displayed marked discoloration. At 2
      yr, the sealers discolored and remained confined primarily to the pulp chamber.

PMID- 12067132
TI  - Sealing ability of mineral trioxide aggregate and super-EBA when used as
      furcation repair materials: a longitudinal study.
AB  - Immediate sealing of furcation perforations enhances the repair process. The
      purpose of this study was to longitudinally compare the ability of mineral
      trioxide aggregate (MTA) and Super-EBA to seal furcation perforations. Fifty-one
      extracted human maxillary molars were decoronated 3 mm above the CEJ, and the
      roots were amputated 3 mm below the furcation. A #2 high-speed round bur was used
      to perforate the center of the furcations. The canals were obturated with gutta
      percha, and the root ends were sealed with C&B Metabond. Three experimental
      groups of 15 teeth each were restored with MTA, Super-EBA, or a combination of
      MTA in the perforation and a Super-EBA dome on the pulpal floor. Six teeth served
      as controls. Each tooth was affixed to a fluid filtration device and subjected to
      a pressure of 20 cm H2O. The integrity of the perforation seal was evaluated
      initially at 30 min for the Super-EBA and the combination groups and at 4 h for
      the MTA group. Additional measurements were then made at 24 h, 1 week, and 1
      month. The controls behaved as expected. A two-way ANOVA revealed a significant
      difference (p = 0.01) between materials. Tukey's test isolated the difference to
      Super EBA as producing a superior seal but only at 24 h. There was no significant
      effect with time (p = 0.57) or the interaction of the materials with time (p =
      0.66). All materials sealed the perforations very well. The maximum leakage of
      all materials was <0.007 microL min(-1) cm H2O(-1).

PMID- 12067133
TI  - Failure mechanism of Hedstroem endodontic files in vivo.
AB  - Intracanal fracture of endodontic Hedstroem files (H-files) jeopardizes the
      outcome of endodontic therapy. The aim of this study was to evaluate the fracture
      mechanism of H-files after multiple in vivo uses. Five each of size #20 and #25
      ISO H-files fractured during clinical use were collected from different dental
      clinics. Four fractured files of each size and three unused files of each
      corresponding size were embedded in a resin along their longitudinal axis and
      after metallographic grinding and polishing studied under an incident light
      microscope. One specimen in the fractured group was investigated under a scanning
      electron microscope. Light microscopy results showed that unused files were free
      of structural defects (cracks, pores, etc.), whereas fractured files demonstrated
      the presence of many cracks mostly located at the flute depth region. Secondary
      cracks were identified beyond the fracture plane of fractured files both with a
      light microscope and a scanning electron microscope. Experimental results
      demonstrated that fatigue is closely associated with the fracture mechanism of H
      files (#20, #25) under clinical conditions.

PMID- 12067134
TI  - Straight line access and coronal flaring: effect on canal length.
AB  - The object of this study was to determine if canal length is altered as a result
      of straight-line access (SLA) and coronal flaring (CF). Selected were 86 canals
      of extracted molars and premolars from two groups: straight or severely curved
      (Schneider curvature <5 degrees and >20 degrees). The reference cusp tip and root
      end were flattened to produce reproducible measurements. A #10 file was placed
      such that the tip extended slightly beyond the apex, with the handle on the
      referenced cusp. The amount of file protrusion was measured with a
      stereomicroscope. Then, SLA and CF were performed and the corresponding file
      replaced to the same coronal reference position. Apical file protrusion was
      measured again. The change in canal length was determined by the difference in
      the pre- and post-SLA/CF measurements. A Wilcoxon signed rank test statistically
      verified that there was a measurable, significant (p < 0.001) change in canal
      length after SLA and CF. The mean change overall was slight, with a decrease of
      0.17 mm. Severe curvature had a slightly greater, significant effect on the
      amount of change. Tooth type had no significant effect. Changes in working length
      from SLA and CF, although statistically significant, were very small and
      clinically unimportant.

PMID- 12067135
TI  - Clinical investigation of second mesiobuccal canals in endodontically treated and
      retreated maxillary molars.
AB  - An examination of 1873 conventionally treated and retreated maxillary first and
      second molars was made in an attempt to determine the percentage of second
      mesiobuccal (MB2) canals that could be located routinely and evaluate if there
      were any significant differences between initial treatments and retreatments. The
      teeth examined were 1193 first molars and 680 second molars treated consecutively
      over a 2-yr period by five endodontists. Overall the MB2 canal was found in 724
      (61%) first molars and 245 (36%) second molars. The incidence of a MB2 canal in
      first molar retreatments was 67% compared to a 59% incidence in initial
      treatments. Whereas in second molars, the retreatment incidence was 44% compared
      with 35% in initial treatments. The significant difference in the incidence of a
      MB2 canal between initial treatments and retreatments suggests that failure to
      find and treat existing MB2 canals will decrease the long-term prognosis.

PMID- 12067136
TI  - Endodontic treatment of unusual central incisors.
AB  - This report presents an endodontic therapy in an unusual case of a patient who
      had wide crowns of both permanent maxillary central incisors. The right maxillary
      central incisor had two separate canals on a fused root and the left had a large
      root canal within one root.

PMID- 12067137
TI  - Zebra XXV, Part 2. Cemento-ossifying fibroma.

PMID- 12067138
TI  - The AAE is listening! American Association of Endodontists.

PMID- 12067139
TI  - Intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial
      embolization for patients with locally advanced uterine cervical cancer.
AB  - Nedaplatin is a platinum analog that has less renal toxicity and higher efficacy
      for uterine cervical cancer than cisplatin. Intraarterial cisplatin has been
      shown to be more effective than intravenous cisplatin in the treatment of
      cervical cancer. To improve the prognosis of cervical cancer, we studied
      combination chemotherapy of intravenous nedaplatin and intraarticular cisplatin
      with transcatheter arterial embolization (TAE). The criteria for selecting
      patients for this study were as follows: age 16-75 years, stage Ib2-IV according
      to the classification of the International Federation of Gynecology and
      Obstetrics (FIGO), performance status between 0 and 2, a creatinine clearance of
      >40 ml/min, adequate bone marrow and adequate renal and hepatic function. Thirty
      two patients, aged 29-72 years (median: 55) were treated. FIGO stage was Ib2 in
      seven patients, IIa in seven patients, IIb in four, IIIa in one, IIIb in seven
      and IVa in six. Twenty-four patients had squamous cell carcinoma, three had
      adenocarcinoma and five had adenosquamous carcinoma. Written informed consent was
      obtained from all patients. Nedaplatin (30-70 mg/m2) was administered
      intravenously on day 1 and cisplatin (70 mg/m2) was administered intraarticularly
      via both uterine arteries on day 3 using the Seldinger method. TAE was then
      performed. This course of treatment was repeated every 3 weeks for 2-3 cycles.
      Response to the therapy was defined by magnetic resonance imaging. Partial
      response was found in 59% patients (19/32) and complete response in 34% (11/32),
      with an overall response rate of 94% (30/32). Myelosuppression was manageable. No
      grade 2 neurotoxicity was observed. The median follow-up was 32 months (6-53
      months), with 84% of patients showing an overall survival of 1 year and 77%
      showing an overall survival of 2 years. These results show that this combination
      chemotherapy effected a high response rate. However, its influence on long-term
      survival remains to be determined.

PMID- 12067140
TI  - Five-day infusion of fluorouracil and vinorelbine for advanced breast cancer
      patients treated previously with anthracyclines.
AB  - Vinorelbine has proven to be effective in pretreated metastatic breast cancer
      patients. In particular, no cross-resistance with anthracyclines has been
      demonstrated. Protracted 5-fluorouracil infusion presents a better
      pharmacological profile than its bolus administration. The aim of this study was
      to investigate the efficacy and toxicity of the combination of these two
      antitumor drugs in patients with metastatic breast cancer who had been previously
      treated with anthracycline-containing regimens. From February 1998 to January
      2000, 65 patients were enrolled into the study The most important inclusion
      criteria were as follows: Karnofsky 70-100, measurable or evaluable disease and
      normal renal, hepatic, bone marrow and cardiac function. Mean age was 48 years
      (range: 31-70). Fourteen of the 65 women had already received more than one
      chemotherapy line. Twenty-three patients had previously been treated with
      taxanes. Sites of involvement were the lungs in 50% of the patients, the liver in
      37%, soft tissue in 72%, bone in 58% and other sites in 32%. Treatment consisted
      of vinorelbine 25 mg/m2 administered on days 1 and 6 every 21 days and 5
      fluorouracil 700 mg/m2/day for 5 consecutive days. The total number of cycles was
      340 (mean: five cycles). The treatment was well tolerated. Febrile neutropenia
      was observed in 4.6% of patients. Fourteen percent of patients experienced grade
      3 or 4 neutropenia, and 3% experienced grade 3 thrombocytopenia. Grade 3
      stomatitis was observed in 9.2% of patients, grade 3 neurologic toxicity was
      observed in 1.5%, and grade 3 cardiotoxicity in 4.6%. Grade 3 site reaction
      occurred in 3% of patients. Sixty patients were evaluated for response. One
      patient (1.7%) attained complete clinical response and 28 (46.7%) attained
      partial response. In 22 patients (36.6%) stable disease was documented and nine
      patients (15%) progressed while on treatment. Median time to progression was 24
      weeks, median duration of response was 35 weeks and median overall survival was
      41 weeks. Vinorelbine with 5-day infusion of 5-fluorouracil presented high
      therapeutic activity in breast cancer patients previously treated with
      anthracyclines, with acceptable toxicity.

PMID- 12067141
TI  - Nonsteroidal antiinflammatory drug-induced mucosal lesions of the upper
      gastrointestinal tract and their relationship to Helicobacter pylori.
AB  - The aim of the present study was to determine the prevalence of Helicobacter
      pylori infection in a group of patients hospitalized at the clinic of
      rheumatology who presented peptic ulcers and erosions associated with
      nonsteroidal antiinflammatory drugs (NSAIDs). Of a group of 4,256 hospitalized
      patients receiving therapy with NSAIDs, 221 patients with persistent dyspepsia
      underwent endoscopic examination of the upper segment of the gastrointestinal
      tract. Among them, mucosal abnormalities in the stomach and duodenum were
      confirmed in 69 patients. H. pylori was found in 42% (29/69) of the examined
      patients. Peptic ulcers were confirmed in 19 patients. Localization was gastric
      in 12 patients and duodenal in seven. H. pylori was found in only 17% of the
      patients (2/12) with gastric ulcers, but in as many as 86% (6/7) of those with
      duodenal ulcers. Patients with H. pylori taking NSAIDs were at higher risk of
      developing duodenal mucosal abnormalities, both ulcers (OR: 10.17; 95% CI: 1.08
      23.88, p = 0.013) and erosions (OR: 2.67; 95 CI: 1.94-3.66, p = 0.001).
      Concomitant administration of corticoids and NSAIDs did not increase the risk of
      gastrotoxicity in patients with positive finding of H. pylori (OR: 0.32; 95% CI:
      0.1-0.96). In conclusion, a close association was found between H. pylori
      infection and duodenal ulcers and erosions, but not between gastric ulcers and
      gastric erosions in a group of patients hospitalized for rheumatic diseases and
      undergoing NSAID therapy.

PMID- 12067142
TI  - Irritable bowel syndrome: attrition rates of patients identified at primary care
      centers during a 50-week period versus those identified in hospitals in a phase
      II clinical trial.
AB  - Although most irritable bowel syndrome (IBS) patients are managed in primary care
      centers, most trials are performed in the hospital setting. A successful
      recruitment strategy is important for trial completeness and its external
      validity. To this end, it was important to assess the attrition rates of patients
      identified at primary care centers and hospitals in this phase II trial conducted
      in the outpatient clinics of 16 hospitals. IBS patients were identified through
      review of the centers' files (prescreening). After a 2-week single-blind placebo
      screening phase, the patients were randomized to receive an investigational drug
      or a matched placebo for 24 weeks (dose-ranging study). Thereafter, the patients
      were invited to participate in a 24-week, double-blind extension study. The
      attrition rates among patients identified at hospitals (group A) and at primary
      care centers (group B) were compared in each study phase and during the 50-week
      period by bivariate and multivariate regression analyses. Group A and B patients
      were identified in 13 hospitals and 51 primary care centers, respectively. Of
      1,001 prescreened patients, 302 started the screening phase with attrition rates
      of 35% (of 132 patients) and 25% (of 170) for groups A and B, respectively (p =
      0.054). The attrition rate during the double-blind phase was 14%. Of the 184
      patients who completed the dose-ranging study, 39 (group A: 32%; group B: 14%; p
      = 0.005) did not wish to participate in the extension study. The attrition rate
      in the extension study was 15%. The overall attrition rates during the 50-week
      period were 67% and 53% (p = 0.016) for groups A and B, respectively. The
      multivariate regression analysis showed that the screening phases (p = 0.000) and
      unwillingness to participate in the extension study (p = 0.007) had the highest
      impact on attrition rates. We conclude that referring patients identified in
      primary care centers to hospitals seems appropriate to ensure potentially
      eligible patients for IBS trials. Patients identified in primary care centers are
      more likely than those identified in hospitals to participate in a 24-week
      extension study, which may be due to their positive feelings about being treated
      in a hospital rather than being referred back to their original primary care
      center. This strategy may be considered in future trials since, with a reasonably
      low attrition rate, it would enhance the external validity of the results
      obtained.

PMID- 12067143
TI  - Population pharmacokinetics, protein binding and antiarrhythmic effects of
      disopyramide enantiomers in arrhythmic patients.
AB  - Disopyramide (DP) is widely used as an antiarrhythmic agent. The antiarrhythmic
      effects of its enantiomers differ from each other and its metabolism and protein
      binding are also stereoselective. Population pharmacokinetic parameters of DP
      racemate, enantiomers (S(+)-DP, R(-)-DP), and their unbound concentrations (uDP,
      S(+)-uDP and R(-)-uDP) were analyzed using the nonlinear mixed effect model
      (NONMEM) program. Data were available from 108 points of 33 arrhythmic patients
      on maintenance therapy with DP racemate. We evaluated the factors to which
      pharmacokinetic parameters are attributed and the relationships between each
      serum concentration and the antiarrhythmic effect. A one-compartment model was
      fitted to the data using NONMEM. For DP, S(+)-DP and R(-)-DP, elimination rate
      constants (kes) were estimated as 0.0648, 0.0663 and 0.0691/h, respectively and
      the mean apparent volume of distribution (Vd/F) were estimated as 63.2, 54.1 and
      71.6 l, respectively. Using the ke and Vd/F values estimated by NONMEM, time
      concentration curves were well fitted to the observed data. Unbound fractions of
      both DP enantiomers showed nonlinearity and the binding ratio of S(+)-DP was 0.84
      +/- 0.07, which was higher than that of R(-)-DP [0.70 +/- 0.11 (p < 0.01)].
      Unbound fractions of both DP enantiomers correlated with alpha1-acid glycoprotein
      (AGP) (p < 0.01). On the other hand, using NONMEM, a significant proportion of
      the variability of Vd/F could be attributed only to AGP (p < 0.001). NONMEM was
      able to clarify the pharmacokinetic features in the protein binding of DP.
      Individual steady state concentrations were estimated by NONMEM using the
      Bayesian method. The average unbound concentrations of all nine responders were
      higher than those of the four non-responders, even though this difference was not
      significant. Unbound concentrations may reflect drug concentrations in the
      tissue, which suggests that these concentrations may indicate an antiarrhythmic
      effect rather than the total concentration.

PMID- 12067144
TI  - Different mechanisms of fibrinolysis impairment among dyslipidemic subjects.
AB  - To determine whether there is a correlation between fibrinolytic activity and
      dyslipidemia, we performed a study of 72 subjects (20 patients with
      hypercholesterolemia, 20 with hypertriglyceridemia, 12 with isolated low high
      density lipoprotein (HDL)-cholesterol (mean age 47.7 +/- 6.3, body mass index
      24.7 +/- 0.4) and 20 healthy controls. Plasminogen activator inhibitor-1 (PAI-1),
      tissue-plasminogen activator activity and plasmin-antiplasmin complexes (PAP)
      were detected at baseline and after venous occlusion test. We also measured at
      baseline lipidic pattern, soluble E and P selectins (sE-sel, sP-sel), prothrombin
      factor 1+2 (F1+2), lipoprotein(a), factor VII, plasma insulin, fibrinogen,
      homocysteine, and thrombin activable fibrinolysis inhibitor (TAFI) activity.
      Fibrinolysis was significantly reduced in hypertriglyceridemic patients compared
      with hypercholesterolemic patients and control subjects (PAP, p < 0.01 and p <
      0.001) and was associated with increased PAI-1 (at baseline and after venous
      occlusion test, p < 0.001). sP-sel, F1 +2 and TAFI were not significantly
      different compared with controls, while hypercholesterolemic subjects showed a
      significant increase in these parameters (p < 0.001), which were related to
      decreased PAP only at the upper low-density lipoprotein (LDL)-cholesterol levels
      (>160 mg/dl) (p < 0.001, r = -0.76). Moreover, there was no significant
      difference in PAI-1 activity (at baseline and after venous occlusion test)
      compared with controls. In conclusion, endothelial dysfunction was the main
      mechanism of decreased fibrinolysis in subjects with hypertriglyceridemia and low
      HDL-cholesterol, while enhanced thrombin generation and TAFI activity were the
      main determinants in hypercholesterolemia.

PMID- 12067145
TI  - Hyperbaric oxygen therapy, multiple sclerosis, and unapproved indications: taking
      a stand.

PMID- 12067146
TI  - Treatment of multiple sclerosis with hyperbaric oxygen therapy.
AB  - Despite considerable research effort there is little controlled evidence that a
      course of hyperbaric oxygen therapy (HBO2T) results in any benefit for patients
      with multiple sclerosis (MS). The great majority of randomized trials involved
      investigating a course of 20 treatments at pressures between 1.75 and 2.5 atm abs
      daily for 60-120 min over 4 wk against a placebo regimen. None has tested the
      efficacy of HBO2T against alternative current best practice. A systematic review
      of this randomized evidence suggests there is no significant benefit from the
      administration of HBO2T (Improved EDSS after HBO2T: OR = 2.02, 95% CI 0.63-6.43.
      Improved sphincter function: OR = 1.3, 95% CI 0.8-2.11). On average, 42 patients
      would need to be treated before we could expect one individual to benefit with an
      improved disability status score; however, we cannot be confident that the number
      we would need to treat is less than infinite (NNT = 42, 95% CI 15 to infinity).
      There is some case for further investigation of possible therapeutic effects in
      selected sub-groups of patients and for the response to prolonged courses of
      HBO2T at more modest pressures; however, the case is not strong. At this time, we
      cannot recommend the routine treatment of MS with HBO2T.

PMID- 12067147
TI  - Ethical dilemmas in hyperbaric medicine.
AB  - Although hyperbaric oxygen therapy (HBO2T) is the primary or adjunctive treatment
      for a limited number of clinical conditions, off-label use is increasing as a
      result of public demand. Because of unusual research problems and limited
      regulatory mechanisms to ensure patient safety, physicians question whether it is
      ethical to provide HBO2T for an unproven indication. An ethical approach to the
      off-label use of HBO2T is proposed. This approach requires combining a
      physician's clinical judgment with guidelines written by recognized organizations
      in hyperbaric medicine and patient informed consent. Scientific guidelines can
      identify which off-label uses of HBO2T are not therapeutic, which are potentially
      therapeutic, and to what degree. Registries or a central repository for the
      systematic collection of data can promote research. Ethical guidelines should
      require patient informed consent for approved indications, for potentially
      therapeutic off-label indications, and for registry or research participation.
      The creation of a consortium of hyperbaric clinics may improve the validity of
      information disseminated to the general public and promote the ethical practice
      of HBO2T.

PMID- 12067148
TI  - Comparison of three different ultrasonic methods for quantification of
      intravascular gas bubbles.
AB  - For evaluating different decompression schedules, the use of ultrasound is
      common. Systems based on the Doppler principle have mostly been used. However,
      ultrasonic scanners producing images where the bubbles are easily detected, may
      be an alternative, because analysis of the signals is simpler than when using
      Doppler methods. In this study, three methods of bubble detection were used
      following a series of air dives. The divers were investigated using a "blind"
      Doppler system where only auditory signals were used for positioning the probe.
      They were also studied using ultrasonic images and finally an "image-assisted"
      Doppler method was used, where the sample volume of the Doppler system was
      positioned using the images. Both Doppler systems were pulsed Doppler systems.
      The agreement between the methods was determined using weighted kappa statistics.
      The results show that, at rest, the agreement between the images and the blind
      Doppler method was very good, and between the two Doppler methods and the images
      and the image-assisted method the agreement was good. Generally, the agreement is
      better at higher bubble grades. After movement, the agreement was not good. We
      conclude that grades from the different methods can be directly compared at rest.

PMID- 12067149
TI  - Thermal insulation properties of argon used as a dry suit inflation gas.
AB  - Uncontrolled observations from the "technical" diving community claim superior
      thermal comfort when replacing air with argon as dry suit inflation gas during
      diving. The objective of the present experiment was to evaluate the effectiveness
      of argon compared to air during cold water diving. Body weight, urinary output,
      and rectal and skin temperatures were measured in six naval divers during two
      dives to approximately 10 m for 60 min. Level of thermal comfort was reported.
      Dry suit gas was either argon or air, divers and scientists were blinded for gas
      identity. Urinary output was approximately 200 ml less (P < 0.05) during the air
      than the argon dives. Rectal and all skin temperatures decreased significantly in
      both groups during the dive but no difference was measured between argon and air
      dives. Thermal comfort was not different between the groups. Replacing air with
      argon neither improves subjective impression of thermal comfort nor attenuates
      core or skin cooling during cold water diving to 10 meters of sea water for 60
      min.

PMID- 12067150
TI  - Acute psychosis associated with diving.
AB  - There are only a few reported cases of psychiatric disorders presenting a s
      decompression sickness (DCS). Previous reports indicate that DCS can result in
      personality change, depression, Munchausen's syndrome, and pseudo stroke. We
      report two cases of acute psychoses that occurred following diving as suspected
      DCS and were treated with hyperbaric oxygen, which did not improve the psychotic
      features. One patient had symptoms of DCS including myalgias, weakness, and
      fatigue; however the symptoms were inconsistent. The symptom onset and nitrogen
      loading from his dive profiles made the diagnosis of DCS unlikely. The second
      patient exhibited mild joint pain, fatigue, and psychosis that was temporally
      associated with diving but no other symptoms of DCS. Following a detailed medical
      evaluation we determined that these two patients did not have DCS or arterial gas
      embolism (AGE). Although it is highly unlikely that a pure psychotic episode will
      arise as a result of DCS, physicians caring for divers with symptoms of DCS or
      AGE and acute psychosis may consider a trial of recompression therapy while
      completing the medical evaluation. Divers with acute psychosis without signs and
      symptoms and benign dive profiles are unlikely to have DCS or AGE.

PMID- 12067151
TI  - Thermal status of saturation divers during operational dives in the North Sea.
AB  - The principal aim of the present study was to monitor the core temperature (Tc)
      of a population of saturation divers conducting routine deep dives at different
      locations in the United Kingdom sector of the North Sea and to assess whether
      current dive procedures are adequate in preventing deleterious decreases in Tc. A
      total of 30 divers, with an average (SD) of 19.3 (6.6) yr of experience as
      saturation divers, participated in the study. The survey included 59 dives
      conducted at six locations (Scott Field, Norfra Pipeline, Hudson Field, Pierce
      Field, Forties Field, and Bruce Field) from four Diver Support Vessels (Rockwater
      1, Semi 2, Bar Protector, and Discovery). The depth of the dives monitored ranged
      from 54 to 160 meters of seawater (msw), and the duration of the dives from 31
      min to 7 h 30 min. before each dive, divers were requested to ingest a radio pill
      and strap a data logger to their abdomen. Upon returning to the chamber within
      the Diver Support Vessel following a dive, they provided subjective ratings of
      thermal perception (7 point scale) and thermal comfort (4 point scale) for the
      period just before, during, and immediately after the dive. In 55 dives, Tc of
      saturation divers working at depths to 160 msw for up to 6 h with water
      temperatures ranging from 4 degrees to 6 degrees C increased above the pre-dive
      core temperature of 37.4 degrees (0.620+/-0.6 degrees C). In four dives there was
      a decrease in Tc: 2 divers had a 0.2 degrees C fall in Tc, and 2 bellmen had a
      decrease of 0.4 degrees and 1.0 degrees C. The subjective responses of divers
      indicated that they were thermally neutral (neither warm nor cold) and
      comfortable before and immediately after the dives. The current practice of
      providing thermal protection with hot water suits to saturation divers working in
      the North Sea is adequate for preventing the risk of hypothermia and maintaining
      thermal comfort.

PMID- 12067152
TI  - Carbon monoxide poisoning: interpretation of randomized clinical trials and
      unresolved treatment issues.
AB  - Since hyperbaric oxygen therapy (HBO2) appeared as a treatment for CO poisoning
      in 1960, whether and when to use it for CO poisoning have often been debated.
      HBO2 has been advocated to treat severe CO poisoning to limit delayed and
      permanent neurologic sequelae. Initially, inferences about efficacy were based on
      clinical experience and uncontrolled studies, but since1989, six prospective
      clinical trials have been reported comparing HBO2 and normobaric O2
      administration to treat patients with acute CO poisoning. Of the six trials, four
      found better clinical outcomes among patients receiving HBO2 while two have shown
      no treatment effect. The most recent and best-designed randomized controlled
      clinical trial, performed in Salt Lake City, supports the efficacy of HBO2 in
      severe acute CO poisoning in accordance with scientific rationale and clinical
      experience. However, a number of important issues remain for future
      investigation, which could be addressed in a large multi-center trial. Such a
      trial should attempt to determine the optimal number of HBO2 treatments and the
      maximum treatment delay from CO poisoning for HBO2 to provide efficacy in
      patients with specific risk factors for a poor outcome.

PMID- 12067153
TI  - Lidocaine in the treatment of decompression illness: a review of the literature.
AB  - While recompression and hyperbaric oxygen administration remain the mainstays of
      treatment for decompression illness (DCI), drugs that might improve outcomes or
      prove beneficial in first aid management have been sought. There has been much
      interest in lidocaine, a sodium channel-blocking agent used clinically as an
      antiarrhythmic and local anesthetic. The relevant literature is reviewed.
      Lidocaine is neuro-protective in cerebral arterial gas embolism (CAGE) in vivo,
      and in a variety of in vivo and in vitro models of ischemic brain injury. There
      has been limited in vivo investigation of efficacy in DCI where bubbles have
      formed from dissolved nitrogen. Mechanisms of neuro-protection by lidocaine
      include deceleration of ischemic ion fluxes across the neuronal cell membrane and
      prevention of the consequent neurotoxic events. In addition, lidocaine lowers
      neuronal metabolism, exerts advantageous effects on cerebral hemodynamics, and is
      a potent anti-inflammatory. There is one randomized double blind study that
      demonstrates improved neuropsychological outcomes in cardiac surgery patients
      receiving lidocaine. Clinical evidence of efficacy in DCI is limited to anecdotal
      reports. Expeditious administration of lidocaine is justified in cases of
      unequivocal CAGE. Speculative use may be justified in severe neurologic DCI after
      patient counseling and consent.

PMID- 12067155
TI  - Ionone derivatives from Alternanthera sessilis.
AB  - The chloroform extract of the air-dried leaves of Alternanthera sessilis afforded
      a mixture of diastereomers of a new ionone derivative 1 whose structures were
      elucidated by extensive 1D and 2D NMR spectroscopy and mass spectrometry.
      Oxidative cleavage of 1 to aldehyde 3 with manganese dioxide confirmed
      diastereoisomerism arose from a racemic side chain chiral centre. Antimicrobial
      tests on the mixture of diastereomers and the derivative indicated that they have
      low activities against Pseudomonas aeruginosa and Trichophyton mentagrophytes.

PMID- 12067156
TI  - Verticillarone: a new seco-fusicoccane diterpenoid ketonepoxide from Hypoestes
      verticillaris.
AB  - The aerial parts of Hypoestes verticillaris (L.F.) Sol. (Acanthaceae) has
      afforded a new seco-fusicoccane diterpenoid ketonepoxide, which was characterized
      as 1(10) seco-fusicocc-3 (4)-ene-5, 11, 14-trione-8 (9), 1 (7)-diepoxide (1) on
      the basis of spectral analysis and named as verticillarone, along with earlier
      reported diterpenoid, i.e. 13-hydroxy-7-oxo-labda-8, 14-diene (2).

PMID- 12067154
TI  - A new biologically active flavonol glycoside from the seeds of Abrus precatorius
      Linn.
AB  - A new flavonol glycoside m.f. C29H34O16, m.p. 260-262 degrees C, [M]+ 638 (EIMS)
      was separated from the chloroform soluble fraction of the concentrated 80%
      methanolic extract of the seeds of Abrus precatorius (Linn). It was characterised
      as a new biologically active flavonol glycoside 7,3',5'-trimethoxy-4'-hydroxy
      flavone-3-O-beta-D-galactosyl-(l --> 4)-alpha-L-xyloside (1) by several colour
      reactions, spectral analysis and chemical degradations.

PMID- 12067157
TI  - Isolation and identification of antioxidants from Sophora japonica.
AB  - A new flavonol triglycoside, kaempferol 3-O-alpha-L-rhamnopyranosyl-(1 --> 6)
      beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside (1), as well as two known
      kaempferol 3-O-[alpha-L-rhamnopyranosyl-(1 --> 6)]-[beta-D-glucopyranosyl-(1 -->
      2)]-beta-D-glucopyranoside (2) and kaempferol 3-O-beta-D-glucopyranosyl-(1 --> 2)
      beta-D-glucopyranoside-7-O-alpha-L-rhamnopyranoside (3), were isolated from the n
      BuOH extract of the pericarps of Sophora japonica by bioassay-guided
      fractionation. The structure of compound 1 was established by UV, IR, MS, and one
      and two-dimensional NMR spectroscopy, including DEPT, NOESY, DQF-COSY, TOCSY,
      HMQC, and HMBC experiments. Compounds 1-3 showed antioxidative activity in DPPH
      and cytochrome-c assay using HL-60 cell system.

PMID- 12067158
TI  - A new lanostane-type triterpene from the fruiting bodies of Ganoderma lucidum.
AB  - A new lanostane-type triterpene, named ganoderic acid LM2 (5), was isolated from
      the fruiting bodies of Ganoderma lucidum. Its structure was characterized as
      (23S) 7beta, -dihydroxy-3, 11, 15-trioxo-5alpha-lanosta-8, 24-dien-26-oic acid by
      1D- and 2D-NMR spectra. In addition, a known triterpene, ganoderic acid epsilon
      (4), was obtained. Both of them exhibited potent enhancement of ConA-induced mice
      splenocytes proliferation in vitro.

PMID- 12067159
TI  - Monoterpenoid derivatives from Paeonia delavayi.
AB  - Three new monoterpene glycosides, 4-O-ethylpaeoniflorin (1), 6'-O-benzoyl-4''
      hydroxy-3"-methoxy-paeoniflorin (2), 6'-O-benzoylalbiflorin (3), and a new
      monoterpenoid, 9-hydroxy-paeonilactone-A (4) were isolated from the root cortex
      of Paeonia delavayi. Their structures were elucidated on the basis of spectral
      methods.

PMID- 12067160
TI  - New xanthone glycosides from Securidaca inappendiculata.
AB  - Three new xanthone glycosides, securixanside A (1), securixanside B (2), and
      securixanside C (3) were isolated from the stems of Securidaca inappendiculata.
      These compounds were characterized by spectrometric and chemical methods,
      including FABMS and one- and two-dimensional NMR experiments.

PMID- 12067161
TI  - Non-taxane compounds from the bark of Taxus yunnanensis.
AB  - From the bark of Taxus yunnanensis, 15 non-taxane compounds were isolated.
      Through spectroscopic methods such as ID and 2D NMR and MS experiments, one of
      them was determined as a new abietane-type diterpenoid named taxayunnin (1). The
      other 14 known compounds were identified as taxamairin C (2), taxamairin A (3),
      3beta-hydroxy-sandaracopimaric acid (4), (+)-3-hydroxy-isodrimenin (5),
      rubrosterone (6), ponasterone A (7), ecdysterone (8), 20-hydroxy-echysone-20,22
      monoacetonide (9), 7-oxositosterol (10), stigmast-4-en-6beta-ol-3-one (11),
      5alpha,6beta-dihydroxy-daucosterol (12), beta-sitosterol (13), daucosterol (14),
      1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-N-(2'-hydroxypalmitoy])-octadeca
      sphinga-4,8-dienine (15), respectively. Compounds 4-6, 9-12 and 15 were isolated
      from Taxus plants for the first time.

PMID- 12067162
TI  - Four new glycosides from Pleurospermum franchetianum.
AB  - Four new glycosides, pleurofranosides I-IV, together with eight known compounds
      were isolated from the whole plants of Pleurospermum franchetianum Hemsl. Based
      on the spectral data and chemical evidence, the structures of pleurofranosides 1,
      II, III and IV were elucidated to be 16beta, 21beta, 23, 28-tetrahydroxyolean-12
      ene-3beta-yl-O-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside, 13beta, 28
      epoxy-16beta, 23-dihydroxyolean-11-ene-3beta-yl-O-beta-D-glucopyranosyl-(1 --> 4)
      [beta-D-glucopyranosyl-(1 --> 2)]-beta-D-fucopyranoside, 13beta, 28-epoxy-16beta,
      23-dihydroxyolean-11-ene-3beta-yl-O-beta-D-glucopyranosyl-(1 --> 4)-[beta-D
      fucopyranosyl-(1 --> 2)]-beta-D-glucopyranoside and 12beta, 28-epoxy-16beta, 23
      dihydroxyolean-11-ene-3beta-yl-O-beta-D-glucopyranosyl-(1 --> 3)-[beta-D
      glucopyranosyl-(1 --> 2)]-beta-D-glucopyranoside. The known compounds identified
      were octadecyl caprate, beta-sitosterol, (22E, 20S, 24R)-5alpha, 8alpha-epidioxy
      ergosta-6, 22-dien-3-beta-ol, daucosterol, alpha-spinasterol-3-O-beta-D
      glucopyranoside, quercetin-3, 7-di-O-beta-D-glucopyranoside, kaempferol-3, 7-di-O
      alpha-L-rhamnopyranoside and kaempferol-3-O-beta-D-glucopyranosyl-7-O-alpha-L
      rhamnopyranoside, respectively.

PMID- 12067163
TI  - Alkaloids from Stemona collinsae.
AB  - A new alkaloid, isostenine (1), together with two known ones neotuberostemonine
      (2) and bisdehydroneotuberostemonine (3) were isolated from the root of Stemona
      collinsae. Their structures were determined by various spectral methods.

PMID- 12067164
TI  - A cytotoxic diterpenoid and antifungal phenolic compounds from Frullania
      muscicola Steph.
AB  - A novel ent-labdane type diterpenoid, muscicolone (1), as well as two bibenzyls
      (2, 3) and four flavonoids (4-7) were isolated from the liverwort Frullania
      muscicola Steph. Their structures were established by analysis of the spectral
      data of IR, UV, ID-, 2D-NMR, and ORD. The stereostructure of 1 was confirmed by X
      ray crystallographic analysis. Bioassay experiments showed that compound 3 and 4
      have potent inhibitory effects against some fungi while 1 showed cytotoxic
      effects to some human tumor cells.

PMID- 12067165
TI  - Bioactive steroids from the brown alga Sargassum carpophyllum.
AB  - By activity-guided fractionation, two new sterols, 3beta,28xi-dihydroxy-24
      ethylcholesta-5,23Z-dien (1) and 2a-oxa-2-oxo-5alpha-hydroxy-3,4-dinor-24
      ethylcholesta-24(28)-ene (2), together with five known steroids, fucosterol (3),
      24-ethylcholesta-4,24(28)-dien-3,6-dione (4), 24xi-hydroperoxy-24
      vinylcholesterol (5), 24-ketocholesterol (6), 24R,28R- and 24S, 28S-epoxy-24
      ethylcholesterol (7), were isolated from the brown alga Sargassum carpophyllum as
      active compounds causing morphological abnormality of Pyricularia oryzae mycelia.
      Compounds 1, 3, 4, 5 and 7 also exhibited cytotoxic activity against various
      cancer cell lines. The IC50 values for 1 and 5 against HL-60 were 7.8 and 8.5
      microg/ml, 3 and 4 against P-388 were 0.7 and 0.8 microg/ml, whereas 7 against
      MCF-7, HCT-8, 1A9, HOS and PC-3 were 4.0, 8.8, 10.0, 10.0 and 7.2 microg/ml,
      respectively.

PMID- 12067166
TI  - Joint meetings of orthopedic associations.

PMID- 12067167
TI  - Coronary artery bypass surgery with heparin-coated perfusion circuits and low
      dose heparinization.
AB  - OBJECTIVE: To evaluate the safety and efficacy of heparin-coated perfusion
      circuits with low-dose heparinization and centrifugal pumping compared with the
      standard method during coronary artery bypass grafting. DESIGN: Prospective,
      randomized, single-blind clinical trial. SETTING: A primary care institution.
      PATIENTS: Ninety patients who underwent first-time elective coronary artery
      bypass grafting were eligible for the study. After giving informed consent, they
      were randomly assigned to 1 of 3 groups (30/group). INTERVENTIONS: Perfusion on
      regular uncoated bypass equipment with a roller pump and full-dose heparinization
      (300 IU/kg bolus, activated clotting time [ACT] > 400 s) (group 1), on a heparin
      coated oxygenator with a centrifugal pump and full-dose heparinization (group 2)
      and on fully heparin-coated bypass equipment with a centrifugal pump and low-dose
      heparinization (100 IU/kg bolus, ACT of 180-400 s) (group 3). Standard coronary
      artery bypass grafting was performed. OUTCOME MEASURES: Postoperative bleeding,
      transfusion requirements and clinical outcomes. RESULTS: There were no
      complications related to the study protocol. Study groups were similar in terms
      of postoperative bleeding, transfusion requirements and clinical outcomes.
      CONCLUSIONS: Heparin-coated cardiopulmonary bypass with low-dose heparinization
      and centrifugal pumping is a safe practice but showed no advantages over the use
      of regular uncoated bypass circuits for coronary bypass surgery.

PMID- 12067168
TI  - Oral versus systemic antibiotic prophylaxis in elective colon surgery: a
      randomized study and meta-analysis send a message from the 1990s.
AB  - OBJECTIVES: To compare the efficacy of combined oral and systemic antibiotics
      (combined) versus systemic antibiotics (systemic) alone in preventing surgical
      site infection in elective surgery of the colon, and to perform a meta-analysis
      of randomized studies comparing combined versus systemic antibiotics in elective
      colon surgery. DESIGN: A double-blind, placebo-controlled, randomized clinical
      trial. SETTING: The Queen Elizabeth Hospital, Montreal, a university-affiliated
      community hospital. PARTICIPANTS: Two hundred and fifteen patients scheduled to
      undergo elective surgery of the colon. INTERVENTIONS: Patients were randomized to
      receive neomycin and metronidazole orally (109 patients) or identical placebos
      (106 patients) on the final preoperative day. All were given amikacin and
      metronidazole intravenously just before operation. Thirteen randomized series
      comparing combined and systemic antibiotic prophylaxis in elective colon surgery
      were identified for meta-analysis. OUTCOME MEASURES: Rates of postoperative
      surgical site infections: risk differences, risk ratios (RRs) and 95% confidence
      intervals (CIs); organisms found in the colon and wound fat at surgery, and in
      infected wounds. RESULTS: Three patients in the systemic group, and 5 in the
      combined group were excluded. Wound infections occurred in 5 patients in the
      combined group but in 17 in the systemic group (p < 0.01, RR = 0.29, 95% CI 0.11
      0.75). Bacteria isolated from wound infections and wound fat were similar to
      those found in the colon. They were more frequent in the colon in the systemic
      group (p < 0.001) and occurred in wound fat in the systemic group twice as often
      as in the combined group (p < 0.001). By stepwise logistic regression, the
      presence of bacteria in wound fat at surgery was the strongest predictor of
      postoperative wound infection (p < 0.002). In the meta-analysis, the summary
      weighted risk difference in surgical site infections between groups (d(w)) and
      the summary RR both favoured combined prophylaxis (d(w) = 0.56, 95% CI 0.26-0.86;
      RR = 0.51, 95% CI 0.24-0.78; p < 0.001). CONCLUSIONS: In elective surgery of the
      colon combined oral and systemic antibiotics are superior to systemic antibiotics
      in preventing surgical site infections. Orally administered antibiotics add value
      by reducing bacterial loading of the colon and wound fat contamination, both
      associated with postoperative wound infection. Meta-analysis of randomized
      clinical trials reported from 1975 to 1995 supports these conclusions.

PMID- 12067169
TI  - Vertebral scalloping in neurofibromatosis type 1: a quantitative approach.
AB  - OBJECTIVE: To investigate quantitative differences in vertebral scalloping
      between children who have scoliosis with and without neurofibromatosis type 1
      (NF1). DESIGN: A retrospective study. SETTING: A university-affiliated children's
      hospital. PATIENTS: Twenty-seven children with scoliosis, 13 of whom had NF1 and
      14 of whom did not. METHOD: Existing radiographs of the lumbar vertebrae were
      used to measure and compare the degree of vertebral scalloping. MAIN OUTCOME
      MEASURES: The distribution of posterior scalloping ratios in the 2 groups and the
      most extreme ratio in each subject in each group were compared. RESULTS:
      Scalloping ratios from the children with NF1 were not normally distributed: 31%
      had ratios greater than 1.20. Scalloping ratios from the non-NF1 children were
      normally distributed, with a mean ratio (and standard deviation) of 1.13 (0.03).
      The distribution between the 2 groups was significantly different (p < 0.05).
      CONCLUSIONS: In children who have scoliosis but no NF1 there was a range of mild
      scalloping whereas those with NF1 has severe scalloping. Further studies are
      needed to determine the possible role of vertebral scalloping in scoliosis
      severity and progression in children who have NF1.

PMID- 12067170
TI  - The effect of epsilon aminocaproic acid on blood loss in patients who undergo
      primary total hip replacement: a pilot study.
AB  - OBJECTIVE: To determine if the use of an antifibrinolytic agent (epsilon
      aminocaproic acid [EACA]) decreased perioperative and postoperative blood loss in
      patients who underwent total hip arthroplasty (THA). DESIGN: A prospective,
      double-blind, randomized, controlled clinical trial. SETTING: A university
      affiliated tertiary care hospital with a large joint arthroplasty population.
      PARTICIPANTS: Fifty-five patients who were scheduled for a primary THA. METHOD:
      Patients were randomly assigned to 2 groups to receive either EACA or saline
      placebo perioperatively. Preoperatively, the groups were similar with respect to
      gender, mean age, mean hemoglobin level, operative time and prosthesis type.
      OUTCOME MEASURES: Blood loss from the start of surgery until the Hemovac drain
      was removed, and the transfusion rate and hemoglobin levels. RESULTS: Mean (and
      standard error) total blood loss for patients receiving EACA was 867 (207) mL and
      for patients receiving placebo was 1198 (544) mL (p < 0.025). Four patients in
      the EACA group received 7 units of packed red blood cells and 7 patients in the
      saline group required 12 units. CONCLUSIONS: Patients receiving the placebo
      sustained greater total blood loss than EACA patients and were more likely to
      require blood transfusion. In the current climate of concern over blood
      transfusions during surgery, EACA administration can reduce blood loss and
      consequently transfusion and transfusion-related risk.

PMID- 12067171
TI  - Lost but not forgotten: patients lost to follow-up in a trauma database.
AB  - OBJECTIVES: To determine the characteristics of patients lost to follow-up and to
      identify if they are significantly different from those who are followed up in
      the context of a prospective randomized controlled trial. DESIGN: A retrospective
      review of a prospectively acquired trauma database. SETTING: A level 1 university
      affiliated trauma hospital. PATIENTS: Two hundred and thirty-six patients treated
      for displaced intra-articular calcaneal fractures between April 1991 and December
      1996. Of these, 198 were catcgorized as "attenders" and the remaining 38 were
      deemed "nonattenders." Demographics, severity of injury, intervention and post
      treatment status of the 2 groups were compared. Demographic information,
      including age, gender, occupation workload, Workers' Compensation Board
      involvement and other standard trauma information were compared and the
      differences analyzed. RESULTS: The nonattenders were younger than the attenders,
      and there was a significantly increased proportion of Aboriginal Canadians in the
      nonattenders group. Attenders were more likely to be "skilled or semi-skilled
      clerical, sales, service or trades crafts" workers, and nonattenders were more
      likely to be "unskilled clerical, sales, service or labour" workers. Attenders
      were more likely to have a preoperative Bohler's angle of < 0 degrees, compared
      with a preoperative Bohler's angle of 0 degrees to 15 degrees for nonattenders.
      CONCLUSIONS: This trauma population is at higher risk of being marginalized by
      society and may not have the same accessibility to a study nurse or a hospital
      contact person. Patients lost to follow-up are a demographically and clinically
      different patient population from those who remain involved in a long-term
      prospective trauma study.

PMID- 12067172
TI  - Morbidity resulting from the treatment of tibial nonunion with the Ilizarov
      frame.
AB  - OBJECTIVE: To determine the sources and magnitude of residual morbidity after
      successful treatment of tibial nonunion using the Ilizarov device and techniques.
      DESIGN: A retrospective cohort study. SETTING: A level 1 trauma centre. PATIENTS:
      Sixteen patients with healed tibial nonunion. INTERVENTION: Application of the
      Ilizarov device and techniques to obtain union of a previous ununited tibial
      fracture. MAIN OUTCOME MEASURES: Patient satisfaction and sources of morbidity
      through clinical review and a visual analogue scale. Two disease-specific outcome
      measurement scales were used to assess ankle dysfunction. Radiographs were
      examined to determine the presence of arthrosis. RESULTS: Residual pain was
      present in over 90% of patients at a mean follow-up of 39 months: in 80% the
      worst pain was in the ankle, less than 10% felt the worst pain in the knee or at
      the fracture site. Mean ankle osteoarthritis scores were 3.4 for pain and 4.0 for
      disability, compared with 0.76 and 0.90 respectively for age-matched controls.
      Mean ankle-hindfoot scores were between 64 and 100. CONCLUSION: Ankle pain with
      disability is the major source of residual disability after successful use of the
      Ilizarov device for the treatment of tibial nonunion.

PMID- 12067173
TI  - Soft-tissue images. Pleuropericardial cyst.

PMID- 12067174
TI  - Musculoskeletal images. Tuberculous osteomyelitis.

PMID- 12067176
TI  - Musculoskeletal case 22. Nail patella syndrome.

PMID- 12067177
TI  - Soft-tissue case 45. Bile peritonitis secondary to transection of the right
      hepatic duct.

PMID- 12067179
TI  - Severe aortic insufficiency associated with left ventricular dysfunction and
      aortic coarctation.

PMID- 12067178
TI  - Anterior approach for repair of an extensive iatrogenic tracheal tear.

PMID- 12067180
TI  - Gradual multiplanar cervical osteotomy to correct kyphotic ankylosing spondylitic
      deformities.

PMID- 12067182
TI  - Authorship for journal articles.

PMID- 12067181
TI  - A new technique for intraoperative analysis of trunk geometry in adolescent
      idiopathic scoliosis.

PMID- 12067184
TI  - Case study: a virtual non-reader achieves a degree.
AB  - J, a mature age student with severe dyslexia, entered university with virtually
      no reading and writing. She could recognize very few words, she had difficulty
      with spelling simple words and her handwriting was poor. She also had distinctive
      difficulties with numbers. Yet, she graduated successfully 3 years after entry.
      In this paper, the characteristics of her disabilities are discussed and the
      teaching programme and support systems set up to help her are described. Some
      theoretical and practical implications which arise from J's case are also
      considered.

PMID- 12067183
TI  - Nasal tip metastasis from esophageal carcinoma.

PMID- 12067185
TI  - A miracle cure? 'tonight with Trevor McDonald', ITV, 21/01/02.

PMID- 12067186
TI  - Involving parents in baseline assessment: employing developmental psychopathology
      in the early identification process.

PMID- 12067187
TI  - The dyslexia ecosystem.
AB  - It is all too easy, in everyday interactions in dyslexia, to see the interactions
      in a semi-adversarial fashion--parents competing to get more support for
      children, researchers competing to get more support for their theories, schools
      trying to get more money for their programmes. Such a set of analyses may be
      described as 'zero-sum'. If one party gains, the other one loses. If, by
      contrast, one views the dyslexia community as a complex, inter-dependent
      'ecosystem', a much more positive view emerges. It becomes clear that there are
      solutions for the system as a whole that are in a sense optimal for the system as
      a whole, solutions that are 'win-win', that is, all parties gain and none lose.
      In this article I develop this concept of the 'dyslexia ecosystem', and outline
      targets that would lead to progress for the ecosystem as a whole.

PMID- 12067188
TI  - A systematic procedure for identifying and classifying children with dyscalculia
      among primary school children in India.
AB  - This paper describes the procedures adopted by two independent studies in India
      for identifying and classifying children with dyscalculia in primary schools. For
      determining the presence of dyscalculia both inclusionary and exclusionary
      criteria were used. When other possible causes of arithmetic failure had been
      excluded, figures for dyscalculia came out as 5.98% (15 cases out of 251) in one
      study and 5.54% (78 out of 1408) in the second. It was found in the latter study
      that 40 out of the 78 (51.27%) also had reading and writing problems. The
      findings are discussed in the light of previous studies.

PMID- 12067189
TI  - A pictographic method for teaching spelling to Greek dyslexic children.
AB  - In the Greek orthography every letter consistently represents the same sound, but
      the same sound can be represented by different letters or pairs of letters. This
      makes spelling more difficult than reading. Two methods of teaching spelling to
      Greek dyslexic children are compared. The first involved pictograms (specially
      drawn pictures) for use when alternative spellings are possible. This is referred
      to as the 'PICTO' method. The second was in effect a combination of two
      traditional methods: the first involved the teaching of letter-sound
      correspondences in a multisensory way; the second involved the use of concepts
      derived from linguistics, the children being taught the derivations of words and
      shown how the same root morphemes, derivative morphemes, etc., were cosistently
      represented by the same spelling pattern. This combination of methods is referred
      to as 'TRAD', signifying 'traditional'. There were 72 subjects in the study, aged
      between 9 and 11 years. Four different teachers, each using both PICTO and TRAD,
      took part in the teaching sessions. The PICTO method proved considerably more
      effective; and possible reasons are suggested as to why this might be so.

PMID- 12067191
TI  - Assessment is not enough: the SPA should participate in constructing a
      comprehensive clinical science of personality. Society of Personality Assessment.
AB  - Several proposals for a comprehensive clinical science of personality are
      enumerated in this Klopfer award article, namely (a) the need to integrate the
      study of personality within a framework of universal principles from which its
      theories can be derived, its categories organized, its assessment tools
      constructed, and its therapeutic interventions designed; (b) the wisdom of
      conceptualizing personality disorders, not as discrete "disease entities" but as
      psychological prototypes; (c) the shift from the Diagnostic and Statistical
      Manual of Mental Disorders Axis I to Axis II distinction to a 3-part complexity
      continuum demarcated by simple reactions, complex syndromes, and personality
      patterns; (d) the utility of expanding the range and comparability of routinely
      appraised clinical domains; and (e) the refining and differentiation of
      personality style and personality pathology subtypes.

PMID- 12067190
TI  - Confessions of an iconoclast: at home on the fringe.
AB  - The career of a psychologist whose work has been on the fringe of psychometrics,
      of personality theory, and, at a stretch, of psychoanalytic theory and the
      philosophy of science is described in this article.

PMID- 12067192
TI  - An examination of interrater reliability for scoring the Rorschach Comprehensive
      System in eight data sets.
AB  - In this article, we describe interrater reliability for the Comprehensive System
      (CS; Exner. 1993) in 8 relatively large samples, including (a) students, (b)
      experienced re- searchers, (c) clinicians, (d) clinicians and then researchers,
      (e) a composite clinical sample (i.e., a to d), and 3 samples in which randomly
      generated erroneous scores were substituted for (f) 10%, (g) 20%, or (h) 30% of
      the original responses. Across samples, 133 to 143 statistically stable CS scores
      had excellent reliability, with median intraclass correlations of.85, .96, .97,
      .95, .93, .95, .89, and .82, respectively. We also demonstrate reliability
      findings from this study closely match the results derived from a synthesis of
      prior research, CS summary scores are more reliable than scores assigned to
      individual responses, small samples are more likely to generate unstable and
      lower reliability estimates, and Meyer's (1997a) procedures for estimating
      response segment reliability were accurate. The CS can be scored reliably, but
      because scoring is the result of coder skills clinicians must conscientiously
      monitor their accuracy.

PMID- 12067193
TI  - Rorschach Aggressive Content (AgC) variable: a study of criterion validity.
AB  - This study adds to the existing literature on the clinical utility of the
      Aggressive Content (AgC) variable proposed by Gacono and Meloy (1994). Criterion
      validity is evaluated by examining the relation between AgC and behavior.
      Rorschach and clinical chart material taken from psychological assessments were
      examined for 94 patients in Exner's (1993) psychiatric reference groups. An
      Aggression Chart Rating Scale (ACRS) was created to score the level of
      aggressiveness of each patient's diagnostic report. Analyses revealed good
      interrater reliability (intraclass correlation coefficient = .73) for ACRS scores
      and Aggressive Movement (AG; kappa = .73) and excellent reliability for AgC
      (kappa =.88) and Morbid Content (MOR: kappa = .79). Pearson's correlation
      revealed significant relations between AgC and both AG and MOR. All 3 Rorschach
      variables were significantly related to scores on the ACRS. A stepwise regression
      analysis utilizing these 3 variables resulted in AgC being the only nonredundant
      predictor of scores on the ACRS. This suggests that AgC was more strongly related
      to more aggressive ACRS scores than either AG or MOR. The continued support for
      the clinical utility of AgC as well as recommendations for the addition of the
      AgC variable to Exner's (1993) Comprehensive System's list of Special Scores are
      discussed.

PMID- 12067194
TI  - Overreport on the MCMI-III: concurrent validation with the MMPI-2 using a
      psychiatric inpatient sample.
AB  - The MCMI-III (Millon, Davis, & Millon, 1997) is a widely used measure of
      personality often used in inpatient psychiatric settings. Although patients in
      such settings often overreport or exaggerate their symptoms, relatively little is
      known about how such a response set presents on the validity indexes of the MCMI
      II. In this study, we used a sample of 191 psychiatric inpatients and compared
      MCMI-III modifier indices (Disclosure, Desirability, and Debasement) with the
      validity measures (L, F, Fb, F(p), K, and F - K) of the MMPI-2 (Butcher,
      Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). In addition, the MCMI-III
      Disclosure Index (Scale X, which imposes a set cutoff score for invalidity due to
      overreport) was compared to several cutoff scores on the validity scales of the
      MMPI-2. Although the MCMI-III indexes generally performed as expected, the MCMI
      III had a very high tolerance for overreport. When contrasted with MMPI-2 F
      scale, the MCMI-II Disclosure Index (which gauges overreport) remained valid
      until scores on MMPI-2 F scale approached a T score of 120. In addition, the
      Disclosure Index was at the upper end or slightly exceeded the highest
      recommended cutoff scores on all other MMPI-2 validity scales except F - K.
      Clinicians using the MCMI-III alone are cautioned to consider the high tolerance
      the MCMI-III has for overreport.

PMID- 12067195
TI  - Development and validation of a couples measure of biased responding: the Marital
      Aggrandizement Scale.
AB  - More than 30 years ago, Edmonds (1967) recognized the need for a couples measure
      of biased responding. Like other categories of self-report instruments, marital
      measures are believed to be highly susceptible to distortion. In this study, we
      describe the development of the Marital Aggrandizement Scale (MAS). For this
      study, item analyses were performed on a subset of responses (n = 200). A priori
      inclusion criteria were applied from which a set of 18 items was selected. Three
      phases of validation research establish the reliability and validity of responses
      to the MAS among an international sample of older married adults (n = 410). The
      concurrent and discriminant validity of responses to this scale is demonstrated
      vis-a-vis separate measures of biased responding, marital satisfaction, and
      psychological well-being. Internal consistency was calculated as alpha = .84.
      Test-retest reliability was calculated as r(200) = .80 over an average interval
      of 15 months. The challenge remains to identify factors associated with the
      etiology and maintenance of this construct. Subsequent research is required to
      identify correlates and antecedents of marital aggrandizement across populations
      over time.

PMID- 12067196
TI  - Applying the big five personality factors to the impostor phenomenon.
AB  - The purpose of this study was to relate the impostor phenomenon (IP) to the Five
      factor model of personality. A sample of 190 college students (79 men, 111 women)
      completed the Clance Impostor Phenomenon Scale (Clance, 1985), the Perceived
      Fradulence Scale (Kolligian & Sternberg, 1991), and the NEO-Personality Inventory
      Revised (Costa & McCrae, 1992). Results of correlational and regression analyses
      support the predicted relations of imposter measures with high Neuroticism and
      low Conscientiousness. Facet-level correlations showed that depression and
      anxiety were particularly important characteristics of those with imposter
      feelings as well as low self-discipline and perceived competence. Implications
      for treatment and future research on the IP are discussed.

PMID- 12067197
TI  - Assessing general maladjustment with the MMPI-2.
AB  - The validities of 7 MMPI-2 (Butcher, Graham, Ben-Porath, Tellegen, & Kaemmer,
      2001) measures of general maladjustment were compared using a composite criterion
      measure based on self-reported symptom severity and clinicians' ratings of
      symptom severity and level of functioning. Participants were 274 male and 425
      female clients at a community mental health center and 105 male and 247 female
      clients at a university psychological clinic. All MMPI-2 measures were
      significantly related to the composite criterion measure for both male and female
      clients in both settings. The mean score on 8 clinical scales (M8) consistently
      was the best indicator of maladjustment. Although other MMPI-2 measures sometimes
      added significantly to the variance accounted for in the criterion measure,
      increments were small and probably not clinically meaningful. However, M8 added
      significantly and meaningfully to each of the other MMPI-2 measures in predicting
      maladjustment. Implications for using the MMPI-2 to assess general maladjustment
      in outpatient mental health settings are discussed.

PMID- 12067198
TI  - Item placement on a personality measure: effects on faking behavior and test
      measurement properties.
AB  - Although personality tests are widely used to select applicants for a variety of
      jobs, there is concern that such measures are fakable. One procedure used to
      minimize faking has been to disguise the true intent of personality tests by
      randomizing items such that items measuring similar constructs are dispersed
      throughout the test. In this study, we examined if item placement does influence
      the fakability and psychometric properties of a personality measure. Study
      participants responded to 1 of 2 formats (random vs. grouped items) of a
      personality test honestly and also under instructions to fake or to behave like
      an applicant. Results indicate that the grouped item placement format was more
      fakable for the Neuroticism and Conscientiousness scales. The test with items
      randomly placed fit the data better within the honest and applicant conditions.
      These findings demonstrate that the issue of item placement should be seriously
      considered before administering personality measures because different item
      presentations may affect the incidence of faking and the psychometric properties
      of the measure.

PMID- 12067199
TI  - Comparing continuous and dichotomous scoring of the balanced inventory of
      desirable responding.
AB  - The Balanced Inventory of Desirable Responding (BIDR; Paulhus, 1994) is a widely
      used instrument to measure the 2 components of social desirability: self
      deceptive enhancement and impression management. With respect to scoring of the
      BIDR, Paulhus (1994) authorized 2 methods, namely continuous scoring (all answers
      on the continuous answer scale are counted) and dichotomous scoring (only extreme
      answers are counted). In this article, we report 3 studies with student samples,
      and continuous and dichotomous scoring of BIDR subscales are compared with
      respect to reliability, convergent validity, sensitivity to instructional
      variations, and correlations with personality. Across studies, the scores from
      continuous scoring (continuous scores) showed higher Cronbach's alphas than those
      from dichotomous scoring (dichotomous scores). Moreover, continuous scores showed
      higher convergent correlations with other measures of social desirability and
      more consistent effects with self-presentation instructions (fake-good vs. fake
      bad instructions). Finally, continuous self-deceptive enhancement scores showed
      higher correlations with those traits of the Five-factor model for which
      substantial correlations were expected (i.e., Neuroticism, Extraversion, and
      Conscientiousness). Consequently, these findings indicate that continuous scoring
      may be preferable to dichotomous scoring when assessing socially desirable
      responding with the BIDR.

PMID- 12067200
TI  - Multiple pathways of cell invasion are regulated by multiple families of serine
      proteases.
AB  - The complex process of tumor invasion requires the coordinated expression and
      activity of cell-substratum adhesive interactions and of cell-associated protease
      systems, which destroy the extracellular matrix (ECM), in order to enable the
      invading cells to simultaneously grip and destroy the anatomical barriers that
      control cell spreading. A number of data indicate that such a 'grip and go'
      process may be performed by an enlarging series of cell membrane-associated
      serine proteases and serine protease receptors, which provide the invasive cells
      with a functional unit (the protease and its receptor), able to mediate cell
      substratum adhesion through specific receptor domains, to proteolytically degrade
      ECM and to deliver into the cell signals that up-regulate the expression either
      of the protease/receptor complex, or of other adhesion molecules, such as
      integrins. There is evidence that some proteases and protease receptor expression
      are under the control of tumor hypoxia, which is the result of an imbalance in
      oxygen supply and demand. The urokinase-type plasminogen activator (u-PA)
      receptor (u-PAR) is under hypoxic control and cooperates with other serine
      proteases of the blood coagulation pathways that may extravasate in the tumor
      milieu as a result of hypoxia-simulated increase of vessel permeability. Other
      serine proteases and their receptors cooperate with the cell-associated
      fibrinolytic system to promote cell invasion. Among these, tissue factor and its
      ligand coagulation factor VII, thrombin and its protease-activated receptors, and
      type II trans-membrane serine proteases seem to play a crucial role. This Review
      takes into consideration the complex scenario of the single serine proteases and
      related receptors that are involved in cell invasion, as well as the protease
      receptor/adhesion molecule interplay which is necessary to focus the cell surface
      driven proteolysis where adhesion provides a grip to the invading cell.

PMID- 12067201
TI  - MT-MMPs play pivotal roles in cancer dissemination.
AB  - Matrix metalloproteinases (MMPs), a family of zinc-binding endopeptidases, play
      important roles in cancer proliferation and dissemination, and may be further
      associated with other diseases. In particular, membrane-type MMPs (MT-MMPs) are
      crucial for cancer cell invasion. In this report, we summarize the current views
      on the role of MT-MMPs in cancer dissemination. The regulated and restricted
      degradation of the extracellular matrix (ECM) surrounding the tumor surface is a
      trigger event for cell protrusion and invasion. This is thought to be primarily
      organized by MT-MMPs, since a shift in balance between cell adhesion molecules,
      ECM and proteolysis at the focal cell surface may result in conditions especially
      suitable for cancer cells to progress and invade the ECM. To resolve the
      physiological mechanisms of cancer invasion and migration, molecular milieu
      surrounding the MT-MMPs expressed on tumor cell surfaces should be further
      examined for each cell type, which may consequently provide a novel clinical tool
      to regulate cancer behavior.

PMID- 12067202
TI  - Role of the alpha3beta1 and alpha6beta4 integrins in tumor invasion.
AB  - Integrin receptors are well-known mediators of cell adhesion that also have a
      fundamental role in controlling the migration of cells through tissues. Among the
      numerous members of a still growing family, two particular molecular complexes
      have turned out to be of key importance in tumor cell invasion of basement
      membranes, the alpha3beta1 and alpha6beta4 integrins. In this Review, we will
      focus on the role of these two receptors and the mechanisms by which they
      influence the invasion process.

PMID- 12067203
TI  - Expression and function of the AMF receptor by human melanoma in experimental and
      clinical systems.
AB  - Motility of tumor cells is the rate limiting potential of metastatic cells and is
      regulated by autocrine and paracrine factors. Autocrine motility
      factor/neuroleukin/phosphohexose isomerase (AMF) is one of the best characterized
      autocrine motogenic cytokines. Here we have studied its in vitro effects on
      several human melanoma cell lines and found that neither cell line exhibited
      mitogenic response to AMF at a concentration where motogenic response could be
      initiated. Similar to previous studies on murine melanoma, activation of the AMF
      receptor upregulated beta3 while it downregulated beta1 integrins at the cell
      surface, inducing an integrin phenotype characteristic for invasive/metastatic
      melanoma. The gp78/AMF receptor protein expression in human melanoma cell lines
      correlated to their in vivo spontaneous metastatic potential. Furthermore, in two
      out of three human melanoma lines the expression significantly increased in the
      primary tumor when spontaneous metastases developed (immunosuppressed newborn rat
      model versus SCID mice). In a prospective study we have also analyzed AMF
      receptor protein expression in primary tumors of 54 skin melanoma patients using
      IHC. These studies revealed three types of AMF receptor phenotype: weak,
      heterogenous and strong expression profile. While in thin tumors
      weak/heterogenous AMFR expression predominated, in thick tumors the strong
      expression profile was predominant. The connection between AMFR expression and
      the invasive/metastatic potential of melanoma was further supported by our
      observation that SSM melanoma in the vertical growth phase expressed this
      motility receptor more strongly than tumors in the radial growth phase.

PMID- 12067205
TI  - Tumors and inflammatory infiltrates: friends or foes?
AB  - The recognition of a role for inflammation in the natural history of a tumor has
      a long record, stretching from the mid-19th century. From the times of Virkow,
      who postulated that cancer originates from inflamed tissues, to Metchnikoff and
      many others, this field has continued to excite (and divide) the scientific
      community. The question as to whether the inflammatory infiltrate helps or
      hinders tumors is still open. In a sense, modern molecular biology has, if
      anything, worsened this dualism, and the literature on this issue shows a
      plethora of conflicting reports. We would like to provide another contribution to
      this topic, which was the subject of a recent brilliant review (Balkwill F and
      Mantovani A. Lancet 2001; 357: 539-45), by focussing more specifically to the
      relation between inflammation and tumor invasion and how this could drive
      rational therapeutic approaches.

PMID- 12067204
TI  - Molecular determinants of human uveal melanoma invasion and metastasis.
AB  - The molecular analysis of cancer has benefited tremendously from the sequencing
      of the human genome integrated with the science of bioinformatics. Microarray
      analysis technology has the potential to classify tumors based on the
      differential expression of genes. In the current study, a collaborative,
      multidisciplinary approach was utilized to study the molecular determinants of
      human uveal melanoma invasion and metastasis. Uveal melanoma is considered the
      most common primary intraocular cancer in adults, resulting in the death of
      approximately 50% of patients affected. Unfortunately, at the time of diagnosis,
      many patients already harbor microscopic metastases, thus underscoring a critical
      need to identify prognostic markers indicative of metastatic potential. The
      investigative strategy consisted of isolating highly invasive vs. poorly invasive
      uveal melanoma cells from a heterogeneous tumor derived from cells that had
      metastasized from the eye to the liver. The heterogeneous tissue explant MUM-2
      led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further
      morphological and functional analyses revealed that the MUM-2B cells were
      epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes)
      highly invasive, and demonstrated vasculogenic mimicry. The MUM-2C cells were
      spindle-like, expressed only a vimentin mesenchymal phenotype, poorly invasive,
      and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B
      vs. the MUM-2C clones resulted in the differential expression of 210 known genes.
      Overall, the molecular signature of the MUM-2B cells resembled that of multiple
      phenotypes--similar to a pluripotent, embryonic-like genotype. Validation of
      select genes that were upregulated and down-regulated was conducted by
      semiquantitative RT-PCR measurement. This study provides a molecular profile that
      will hopefully lead to the development of new molecular targets for therapeutic
      intervention and possible diagnostic markers to predict the clinical outcome of
      patients with uveal melanoma.

PMID- 12067206
TI  - IFNgamma and TNFalpha account for a pro-clonogenic activity secreted by activated
      murine peritoneal macrophages.
AB  - In the present study, we found that murine peritoneal macrophages elicited by BCG
      or Listeria monocytogenes release into the media an activity capable of
      stimulating the lung colonization as well as the expression of MHC class I
      antigens in B16 melanoma cells. A similar activity has previously been found in
      media conditioned by Corynebacterium parvum-elicited macrophages. Analysis by gel
      filtration chromatography of media conditioned by Corynebacterium parvum-, BCG-
      or Listeria monocytogenes-elicited macrophages revealed that the material
      responsible for the pro-clonogenic activity concentrated in chromatographic
      fractions corresponding to molecular weights (25 to 52 kDa) which are
      characteristic of certain cytokines. Thus, we challenged the various macrophage
      conditioned media with polyclonal antibodies against IFNgamma and TNFalpha, and
      found that the macrophage pro-clonogenic activity was completely abolished in the
      presence of anti-IFNgamma antibodies, but only partially inhibited by anti
      TNFalpha antibodies. This finding suggests a cooperative participation of the two
      cytokines to the pro-clonogenic activity of the media conditioned by
      Corynebacterium parvum-, BCG- or Listeria monocytogenes-elicited macrophages.

PMID- 12067207
TI  - Signal transduction targets in invasion.
AB  - The processes of physiologic and malignant invasion use the same cellular
      pathways, albeit under differential regulation. Critical signaling messages can
      be initiated through cell-cell and cell-substratum contact, as well as using
      autocrine and paracrine activation. Cancer cells are known for their flexibility
      and autocrine functions, however, they still rely on a battery of important
      signaling events. The interaction between the tumor cell and the stroma provides
      an important signaling milieu and target zone for molecular therapeutic
      intervention. It is now recognized that malignant invasion requires that
      interaction for optimal signaling and function. New technologies are now
      available to allow more rapid dissection of these pathways and characterization
      of unique regulatory sites for therapeutic gain.

PMID- 12067208
TI  - Lampbrush chromosomes and associated bodies: new insights into principles of
      nuclear structure and function.
AB  - The lampbrush chromosomes and assorted nuclear bodies of amphibian and avian
      oocytes provide uniquely advantageous and amenable experimental material for cell
      biologists to study the structure and function of the eukaryotic nucleus, and in
      particular to address the processes of nuclear gene expression. Recent findings
      discussed here include the molecular analysis of the actively elongating RNA
      polymerase complexes associated with lampbrush chromosome loops and of the
      association between loop nascent transcripts and RNA processing components. In
      addition, several types of chromosome structure that do not outwardly resemble
      simple extended loops and that may house novel nuclear functions have recently
      been studied in detail. Among these a type of chromosomal body that can also
      exist free in the oocyte nucleus, the Cajal body, has been shown to possess a
      range of characteristics that suggest it is involved in the assembly of
      macromolecular complexes required for gene expression. Homologous structures have
      also been described in somatic nuclei. Fundamental aspects of the looped
      organization exhibited by lampbrush as well as other chromosomes have also been
      addressed, most notably by the application of a technique for de-novo chromosome
      assembly.

PMID- 12067209
TI  - DNA in the centromeric heterochromatin of polytene chromosomes is topologically
      open.
AB  - Heterochromatin differs from euchromatin by a set of specific features. We
      suggested earlier that specific features of heterochromatin result from
      differences in DNA topology of these two chromatin types and provided
      explanations for the majority of them (Gruzdev 2000). We proposed that, unlike
      topologically closed euchromatic DNA, the DNA of heterochromatin is topologically
      open, i.e. it likely contains single- or doublestrand breaks. In this work, we
      studied the topological state of DNA in a block of centromeric heterochromatin
      and in a euchromatic banded region of Chironomus melanotus polytene chromosomes
      by microfluorimetric methods using the fluorescent intercalating dye ethidium
      bromide (EB). It was demonstrated that the fraction of topologically closed DNA
      in heterochromatin blocks is five-fold smaller than in the banded region. The
      data obtained support the hypothesis proposed.

PMID- 12067210
TI  - The genome phylogeny of domestic cat, red panda and five mustelid species
      revealed by comparative chromosome painting and G-banding.
AB  - Genome-wide homology maps among stone marten (Martes foina, 2n = 38), domestic
      cat (Felis catus, 2n = 38), American mink (Mustela vison, 2n = 30), yellow
      throated marten (Martes flavigula, 2n = 40), Old World badger (Meles meles, 2n =
      44), ferret badger (Melogale moschata, 2n = 38) and red panda (Ailurus fulgens,
      2n = 36) have been established by cross-species chromosome painting with a
      complete set of stone marten probes. In total, 18 stone marten autosomal probes
      reveal 20, 19, 21, 18 and 21 pairs of homologous chromosomal segments in the
      respective genomes of American mink, yellow-throated marten. Old World badger,
      ferret badger and red panda. Reciprocal painting between stone marten and cat
      delineated 21 pairs of homologous segments shared in both stone marten and cat
      genomes. The chromosomal painting results indicate that most chromosomes of these
      species are highly conserved and show one-to-one correspondence with stone marten
      and cat chromosomes or chromosomal arms, and that only a few interchromosomal
      rearrangements (Robertsonian fusions and fissions) have occurred during species
      radiation. By comparing the distribution patterns of conserved chromosomal
      segments in both these species and the putative ancestral carnivore karyotype, we
      have reconstructed the pathway of karyotype evolution of these species from the
      putative 2n = 42 ancestral carnivore karyotype. Our results support a close
      phylogenetic relationship between the red panda and mustelids. The homology data
      presented in these maps will allow us to transfer the cat gene mapping data to
      other unmapped carnivore species.

PMID- 12067211
TI  - Towards unlimited colors for fluorescence in-situ hybridization (FISH).
AB  - We describe a FISH protocol that allows rehybridization of complex DNA probes up
      to four times to the same specimen. This strategy, which we termed ReFISH, opens
      a wide range of new applications to conventional band pass filter epifluorescence
      microscopy. These include M-FISH karyotyping and cross-species color banding that
      emulate multiplex probe sets labeled with up to 12 fluorochromes in sequential
      hybridizations to the same specimen. We designed a human 24-color karyotyping
      probe set in combination with a 29-color cross-species color banding probe set
      using gibbon painting probes. Applying the ReFISH principle, 53 painting probes
      on individual metaphases were discriminated. This allowed simultaneous screening
      for inter- and intrachromosomal rearrangements on normal human diploid cells, a
      HeLa derived cell line, and highly rearranged gibbon chromosomes. Furthermore,
      the present ReFISH experiments successfully combine 24-color FISH with laser
      scanning confocal microscopy to study the 3D organization of all 46 human
      chromosome territories in individual interphase cell nuclei.

PMID- 12067212
TI  - An easy procedure for cytogenetic analysis of aged chromosome preparations using
      FISH-WCP probes.
AB  - Fluorescence in-situ hybridization using whole chromosome probes (FISH-WCP) has
      become the methodology of choice of most cytogenetic laboratories. However, good
      hybridization results are often associated with sample quality, storage
      conditions, and the age of metaphase preparations. Particularly, aging metaphase
      preparations over a prolonged period of time has been considered a critical and
      limiting factor in FISH success. This study reports on the successful use of the
      FISH-WCP procedure to hybridize chromosome preparations that were aged for
      approximately 12 years. Biological samples consisted of 4 individuals
      accidentally exposed to cesium-137 in Goiania (Brazil) in 1987 and 1 control
      individual. Metaphase spreads were obtained from conventionally PHA-stimulated T
      lymphocytes from peripheral blood. Aged slides underwent treatment with Carnoy's
      fixative for 16 h, followed by exposing the slides to water-bath vapour at 60
      degrees C for 4 h. During analysis, chromosome type aberrations, including
      translocations, acentric fragments, and dicentrics were observed. The results
      suggested that it is possible to validate the use of FISH-WCP as a method of
      choice to study aged chromosome preparations, even if the slides were stored in
      undesirable conditions of temperature and humidity. Under these circumstances,
      the procedure could possibly be used as a potent tool in retrospective dosimetry.

PMID- 12067214
TI  - Oligoclonal interspecific origin of 'North Indian' and 'Chinese' sugarcanes.
AB  - Sugarcanes consist of several groups of complex polyploid forms. The origin of
      'North Indian' and 'Chinese' sugarcanes (referred to as S. barberi and S.
      sinense) was investigated using genomic in-situ hybridization (GISH), detection
      of species-specific repeated sequences and RFLP. GISH proved their interspecific
      hybrid origin. Together with the distribution of species-specific repeated
      sequences and earlier RFLP data, the results show that both taxa are derived from
      interspecific hybridization between S. officinarum and S. spontaneum and that no
      other genus has been directly involved. RFLP indicates that the clones are
      clustered into a few groups, each derived from a single interspecific hybrid that
      has subsequently undergone a few somatic mutations. These groups correspond quite
      well with those already defined based on morphological characters and chromosome
      numbers. However, the calculated genetic similarities do not support the
      existence of two distinct taxa. The 'North Indian' and 'Chinese' sugarcanes
      represent a set of horticultural groups rather than established species.

PMID- 12067215
TI  - Biliary complications of pancreatic necrosis.
AB  - BACKGROUND: Involvement of the biliary tract in pancreatic necrosis is rare. The
      authors are presenting six patients with this unusual complication. METHODS:
      Retrospective analysis of a case series. RESULTS: The necrotic process involved
      the bile duct in four patients (bile duct alone in two and bile duct with
      duodenum in two) and the gall bladder in two patients. It was not possible to
      make a preoperative diagnosis of biliary tract involvement in any of these
      patients. The lesions in the biliary tract were caused by the direct erosion by
      the necrotic tissue in five patients, and in one patient with gangrene of the
      gall bladder, it was a "remote" complication of the necrotizing process. All
      patients underwent surgery. Necrosectomy and cholecystectomy were performed in
      patients with gall bladder lesions, and proximal biliary drainage was the method
      of choice in patients with erosion of the bile duct. One patient died
      postoperatively. During follow-up, another patient who had bile-duct involvement
      developed a stricture in the damaged part of the bile duct and needed
      hepaticojejunostomy CONCLUSIONS: Necrotizing pancreatitis can involve the biliary
      tract, both by direct extension and by its secondary effects. Although
      cholecystectomy is the treatment of choice in the presence of gallbladder
      involvement, proximal biliary diversion may be indicated in patients with erosion
      of the bile duct.

PMID- 12067213
TI  - The impact of p53 loss on murine plasmacytoma development.
AB  - Mouse plasmacytomas (PCTs) are characterized by c-myc-activating translocations
      that juxtapose c-myc on chromosome 15 onto one of the immunoglobulin loci (IgH on
      chromosome 12, IgK on chromosome 6, or IgA on chromosome 16). To assess the
      impact of p53 loss on PCT genesis, we induced PCTs in p53-deficient BALB/cRb6.15
      mouse strains. We show that p53 loss accelerates tumor development and causes a
      shift in the typical translocation patterns. PCTs that carry variant T(6;15)
      translocations become as frequent as those with typical T(12;15) translocations
      (41.66%). In addition, in the absence of p53, the number of translocation
      negative PCTs increases from less than 1% to 16.66%. It is noteworthy that
      neither the shortened latency periods nor the shift in translocation patterns had
      an impact on the incidence of PCT development. The 42.2% incidence in N3p53-/-
      mice is similar to the percentages recorded in groups of conventional BALB/cAn
      mice. The possible mechanisms underlying the accelerated tumorigenesis and the
      shift in translocation patterns are discussed.

PMID- 12067216
TI  - Inducible nitric oxide synthase (iNOS) immunoreactivity and its relationship to
      cell proliferation, apoptosis, angiogenesis, clinicopathologic characteristics,
      and patient survival in pancreatic cancer.
AB  - BACKGROUND: The clinicopathological and biological significance of the expression
      of iNOS in pancreatic cancer remains unclear. The goal of this study was to
      determine the possible roles and clinical significance of iNOS expression in
      pancreatic cancer. METHODS: Seventy-two pancreatic adenocarcinoma tissue
      specimens were obtained by surgical resection. We investigated the
      immunohistochemical expression of iNOS in 72 patients with pancreatic cancer with
      respect to variable clinicopathological characteristics, proliferation activity
      (assessed by Ki-67 expression), apoptosis (assessed by TUNEL stain), and
      microvessel density (assessed by CD34 expression; angiogenesis). RESULTS:
      Immunohistochemical investigations demonstrated immunolabeling of tumor cells
      with anti-iNOS antibody. Positivity for iNOS was observed in 48/72 (66.7%). The
      expression of iNOS protein did not correlate with age, bilirubin, tumor marker,
      location, size, AJCC stage, differentiation, distant metastasis, or patient
      survival. No significant association was found between iNOS expression and
      proliferation or microvessel density in pancreatic cancer. Apoptotic index (AI)
      of positive iNOS expressions were significantly higher than negative expression
      (p < 0.001). CONCLUSION: Inducible nitric oxide synthase (iNOS) is expressed by
      human pancreatic cancer, and its presence is positively correlated with apoptosis
      of cancer cells that could provide the basis for the development of therapeutic
      strategies in human pancreatic cancer.

PMID- 12067218
TI  - Primary tuberculosis of the pancreas mimicking a pancreatic tumor.
AB  - BACKGROUND: Diagnosis of tuberculosis of the pancreas is often missed, and may
      present to the clinician as a difficult diagnostic problem. METHODS: We report an
      extremely rare case of a 35-year-old woman who admitted for acute pain in the
      right upper quadrant, jaundice, fever 38 degrees C and chills. During the last 8
      mo, she developed increasing fatigue and a weight loss of approx 10 kg. RESULTS:
      Computed tomography (CT) of the abdomen showed a mass in the head of the
      pancreas, and upper gastrointestinal endoscopy revealed a stenosis of the second
      part of duodenum and a pancreatico-duodenum fistula. Frozen sections by direct
      trucut needle biopsy raised suspicions of a malignancy, and a Whipple procedure
      was performed as a radical procedure. The final histopathology revealed a chronic
      granulomatous lesion with caseating necrosis. Mycobacterium of tuberculosis was
      detected using the polymerase chain reaction-based assay. CONCLUSION: This
      unusual case emphasizes that in suspected cases of pancreatic carcinoma with an
      atypical presentation, an attempt should be made to confirm the diagnosis by CT
      guided needle biopsy, or by ultrasound endoscopic fine-needle aspiration.

PMID- 12067217
TI  - Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal
      papillary mucinous neoplasms.
AB  - BACKGROUND: Pancreatic intraductal papillary mucinous neoplasms (IPMN),
      morphologically resembling colonic adenomas, often have an indefinable malignant
      potential. We used a monoclonal antibody (MAb) raised against colonic adenomas,
      Adnab-9, to identify patients with a better prognosis. METHODS: We assessed Adnab
      9-labeled sections of these neoplasms from 50 patients, 13 pancreatic
      adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical
      techniques. RESULTS: 26% of the IPMNs labeled with Adnab-9 as compared to 0% of
      pancreatic ductal cancers or surrounding benign tissues, (p < 0.001) and 53% of
      adenomas (p < 0.025). Labeling in IPMNs was usually seen in the noninvasive
      epithelium suggesting that Adnab-9 is a premalignant marker in these lesions.
      Labeling of invasive IPMN's identified a group of patients with a superior
      overall survival (p = 0.027). CONCLUSION: Adnab-9 labeling-characteristics appear
      similar for both IPMNs and adenomatous polyps, suggesting that they are analogous
      lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive
      intraductal papillary mucinous neoplasms.

PMID- 12067219
TI  - Is glucagonoma of the pancreas a curable disease?
AB  - BACKGROUND: Glucagonomas are rare neuroendocrine tumors of the pancreas. Because
      of its rarity, its natural history is not well understood. AIM: We evaluated the
      natural history of glucagonomas treated at a tertiary care cancer center.
      METHODS: A retrospective analysis of 12 patients during 1970 to 2000 was
      performed. Six patients (50%) had a tumor located in the head of the pancreas.
      RESULTS: Abdominal pain (83%) and weight loss (75%) were the most common
      symptoms. Median tumor size was 6 cm (range 0.04-10). Seven patients (58%) had
      liver metastases. Five patients (42%) underwent curative resection. Overall
      median survival was 66 mo, and 5-yr overall survival was 66%. Five-yr overall
      survival was 83% for patients who had resection versus 50% for the non-resected
      patients (p = 0.04). Patients who were disease-free had a complete resection of
      the primary tumor and no liver involvement. CONCLUSIONS: Glucagonomas generally
      present with liver metastases at the time of diagnosis. Cure is only possible if
      the disease is localized and completely resected.

PMID- 12067220
TI  - Effects of mast-cell stabilization in cerulein-induced acute pancreatitis in
      rats.
AB  - AIM: In this study we aimed to clarify the role of mast cells in the development
      and progression of inflammation in cerulein-induced acute pancreatitis (AP) in
      rats. We have also examined the effects of ketotifen; a mast-cell stabilizing
      agent in the treatment of acute pancreatitis and its relation with nitric oxide
      (NO) synthesis. METHODS: In the first part of the study we planned to examine the
      effects mast cell stabilization in acute pancreatitis, while the second part was
      focused on examining the relation between NO synthesis and the potential effects
      of ketotifen in AP. Wistar albino rats were randomly divided into 6 groups (n:
      10). In the first part of the study, AP was induced by four subcutaneous (sc)
      injections of 20 microg/kg body weight of cerulein at hourly intervals in Groups
      A and B while Group C was treated with saline as the control group. Group B was
      pretreated with ketotifen 1 mg/kg (ip). In the second part, the study design was
      similar except for the inhibition of nitric oxide synthesis by N-nitro L-arginine
      methyl ester (L-NAME) 30 mg/kg (ip) in Groups D, E and F. Group D was treated
      with L-NAME and cerulein and Group E was treated with ketotifen, L-NAME and
      cerulein. Group F was treated with L-NAME and saline as the control group. Serum
      amylase activity and pancreatic myeloperoxidase activity (MPO) were measured.
      Pancreatic histology and mast-cell count in pancreatic tissue were evaluated.
      RESULTS: Mast cell count was found to be increased in the pancreatic tissue in
      cerulein-induced AP. (2.93+/-0.26 vs 1.98+/-0.26; p<0.001). Ketotifen treatment
      significantly reduced cerulein induced edema (1.30+/-0.21 vs 0.70+/-0.15;
      p<0.001), neutrophil infiltration (1.50+/-0.16 vs 0.60+/-0.16; p<0.001) and
      attenuated the increase in amylase (4394.0+/-149.5 U/L vs 3350.5+/-216.9 U/L;
      p<0.05) and MPO activity (1.14+/-0.13 U/gr tissue vs 0.54+/-0.08 U/gr tissue;
      p<0.001). Mast-cell count in pancreatic tissue was also decreased significantly
      with ketotifen pretreatment (2.93+/-0.26 vs 1.70+/-0.21; p<0.05). Inhibition of
      NO synthesis with L-NAME treatment decreased the beneficial effects of ketotifen.
      CONCLUSION: It seems likely that mast cell activity may play an important role in
      the initiation and progression of acute pancreatitis. Ketotifen treatment may
      reduce the severity of AP in rats. The protective action of ketotifen in cerulein
      induced acute pancreatitis is most probably owing to mast cell stabilization and
      stimulation of NO synthesis.

PMID- 12067221
TI  - Pancreatic polypeptide secretion in patients with chronic pancreatitis and after
      pancreatic surgery.
AB  - AIM: We investigated polypeptide (PP) secretion under basal conditions, in
      response to bombesin infusion and to meal ingestion in patients with chronic
      pancreatitis (CP) and patients after different types of pancreatic surgery.
      METHODS: Included were patients with CP without (n = 20) and with (n = 30)
      exocrine pancreatic insufficiency, patients after duodenum preserving resection
      of the head of the pancreas (DPRHP; n = 20), after Whipple's procedure (n = 19),
      following distal pancreatectomy (DP; n = 12), and healthy controls (n = 36).
      RESULTS: In CP patients basal and bombesin stimulated PP levels were
      significantly (p<0.01) reduced compared to controls only when exocrine
      insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01
      0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma
      PP peak increments after bombesin and meal ingestion correlated significantly
      with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had
      low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic
      pancreatitis. In patients after pancreatic surgery that included pancreatic head
      resection (DPRHP or Whipple operation) basal and stimulated PP secretion were
      significantly (p<0.01-0.05) reduced. CONCLUSION: Basal and meal or bombesin
      stimulated PP levels are significantly reduced in patients with CP only when
      exocrine insufficiency is present. Determination of plasma PP levels has low
      sensitivity and is not useful in detecting chronic pancreatitis without exocrine
      insufficiency. In patients after pancreatic surgery, PP secretion is dependent on
      the type of operation (head vs tail resection).

PMID- 12067222
TI  - Beta-amyloid catabolism: roles for neprilysin (NEP) and other metallopeptidases?
AB  - The steady-state level of amyloid beta-peptide (Abeta) represents a balance
      between its biosynthesis from the amyloid precursor protein (APP) through the
      action of the beta- and gamma-secretases and its catabolism by a variety of
      proteolytic enzymes. Recent attention has focused on members of the neprilysin
      (NEP) family of zinc metalloproteinases in amyloid metabolism. NEP itself
      degrades both Abeta(1-40) and Abeta(1-42) in vitro and in vivo, and this
      metabolism is prevented by NEP inhibitors. Other NEP family members, for example
      endothelin-converting enzyme, may contribute to amyloid catabolism and may also
      play a role in neuroprotection. Another metalloproteinase, insulysin (insulin
      degrading enzyme) has also been advocated as an amyloid-degrading enzyme and may
      contribute more generally to metabolism of amyloid-forming peptides. Other
      candidate enzymes proposed include angiotensin-converting enzyme, some matrix
      metalloproteinases, plasmin and, indirectly, thimet oligopeptidase (endopeptidase
      24.15). This review critically evaluates the evidence relating to proteinases
      implicated in amyloid catabolism. Therapeutic strategies aimed at promoting
      A,beta degradation may provide a novel approach to the therapy of Alzheimer's
      disease.

PMID- 12067223
TI  - Theory relating in vitro and in vivo microdialysis with one or two probes.
AB  - In this paper, we further develop the general theory of microdialysis by
      extending the linear model of Bungay et al. to provide a theoretical basis for in
      vitro and in vivo microdialysis. Specifically, we considered the effect of active
      clearance processes on in vivo microdialysis, and thereby elaborated the theory
      of Benveniste et al. to endogenous compounds. We examined the use of steady state
      tissue diffusion resistance with negligible clearance processes to interpret
      microdialysis data. The influence of the tissue properties on the in vitro and in
      vivo recoveries in dual-probe microdialysis was analyzed and we simulated the
      effect of the operating parameters on dual probe microdialysis performance. We
      estimated that the minimum clearance rate constant detectable by microdialysis in
      a quasi-steady state is about 5.5 x 10(-5) s(-1). This minimum rate constant
      establishes a criterion, below which inhibition of the active clearance processes
      does not show detectable influences on the microdialysis extraction efficiency.

PMID- 12067224
TI  - 5-s-Cysteinyl-conjugates of catecholamines induce cell damage, extensive DNA base
      modification and increases in caspase-3 activity in neurons.
AB  - A decrease in reduced glutathione levels in dopamine containing nigral cells in
      Parkinson's disease may result from the formation of cysteinyl-adducts of
      catecholamines, which in turn exert toxicity on nigral cells. We show that
      exposure of neurons (CSM 14.1) to 5-S-cysteinyl conjugates of dopamine, L-DOPA,
      DOPAC or DHMA causes neuronal damage, increases in oxidative DNA base
      modification and an elevation of caspase-3 activity in cells. Damage to neurons
      was apparent 12-48 h of post-exposure and there were increases in caspase-3
      activity in neurons after 6 h. These changes were paralleled by large increases
      in pyrimidine and purine base oxidation products, such as 8-OH-guanine suggesting
      that 5-S-cysteinyl conjugates of catecholamines are capable of diffusing into
      cells and stimulating the formation of reactive oxygen species (ROS), which may
      then lead to a mechanism of cell damage involving caspase-3. Indeed,
      intracellular ROS were observed to rise sharply on exposure to the conjugates.
      These results suggest one mechanism by which oxidative stress may occur in the
      substantia nigra in Parkinson's disease.

PMID- 12067225
TI  - Functional significance of nitric oxide in ionomycin-evoked [3H]GABA release from
      mouse cerebral cortical neurons.
AB  - We investigated a role of nitric oxide (NO) on ionomycin-evoked [3H]GABA release
      using mouse cerebral cortical neurons. lonomycin dose-dependently released
      [3H]GABA up to 1 microM. The extent of the release by 0.1 microM ionomycin was in
      a range similar to that by 30 mM KCl. The ionomycin (0.1 microM)-evoked [3H]GABA
      release was dose-dependently inhibited by NO synthase inhibitors and hemoglobin,
      indicating that the ionomycin-evoked [3H]GABA release is mediated through NO
      formation. The inhibition of cGMP formation by 1H-[1,2,4] oxodizao [4,3-a]
      quinoxalin-1-one (ODQ), a selective inhibitor for NO-sensitive guanylate cyclase,
      showed no affects on the ionomycin-evoked [3H]GABA release. Tetrodotoxin and
      dibucaine significantly suppressed the ionomycin-evoked [3H]GABA release and
      ionomycin increased fluorescence intensity of bis-oxonol, suggesting the
      involvement of membrane depolarization in this release. The ionomycin-evoked
      [3H]GABA release was maximally reduced by about 50% by GABA uptake inhibitors.
      The concomitant presence of nifedipine and omega-agatoxin VIA (omega-ATX),
      inhibitors for L- and P/Q-type voltage-dependent calcium channels, respectively,
      caused the reduction in the ionomycin-evoked release by about 50%. The
      simultaneous addition of nifedipine, omega-ATX and nipecotic acid completely
      abolished the release. Although ionomycin released glutamate, (+)-5-methyl-1-,11
      dihydro-5H-dibenzo-[a,d]cycloheptan-5,10-imine (MK-801) and 6,7
      dinitroquinoxaline-2,3-dione (DNQX) showed no effects on the ionomycin-induced
      [3H]GABA release. Based on these results, it is concluded that NO formed by
      ionomycin plays a critical role in ionomycin-evoked [3H]GABA release from the
      neurons.

PMID- 12067226
TI  - Functional and molecular characterization of metabotropic glutamate receptors
      expressed in rat striatal cholinergic interneurones.
AB  - In the present study we have used single-cell RT-PCR in conjunction with
      electrophysiology to examine the expression and functional properties of
      metabotropic glutamate receptors (mGluRs) expressed within biochemically
      identified cholinergic interneurones in the rat striatum. Using single-cell RT
      PCR, it was possible to demonstrate the presence of mGluR1, mGluR2, mGluR3,
      mGluR5 and mGluR7 mRNAs within single cholinergic interneurones. Bath application
      of the non-selective mGluR agonist (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic
      acid (1 S,3R-ACPD) or the group-I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG)
      depolarized all cholinergic neurones tested by activation of an inward current at
      -60 mV. The effects of DHPG were partially inhibited by the mGluR5 selective
      antagonist 6-methyl-2-(pherazo)-3-pyridinol and by the non-selective group-I
      antagonist alpha-methyl-4-carboxyphenylglycine but were not mimicked by the group
      II and group-III selective mGluR agonists 2-(2,3-dicarboxycyclopropyl)glycine
      (DCG-IV) and L-2-amino-4-phosphonobutanoate (L-AP4), respectively. Intrastriatal
      stimulation evoked an excitatory postsynaptic current within cholinergic neurones
      that was reversibly inhibited by bath application of the group-II and group-III
      selective mGluR agonists DCG-IV and L-AP4, respectively, via presynaptic actions.
      In summary, we have identified the mGluRs expressed by striatal cholinergic
      interneurones and demonstrated that their activation produces modulatory effects
      via both pre- and postsynaptic mechanisms.

PMID- 12067227
TI  - The degenerative effect of a single intranigral injection of LPS on the
      dopaminergic system is prevented by dexamethasone, and not mimicked by rh-TNF
      alpha, IL-1beta and IFN-gamma.
AB  - It is becoming widely accepted that the inflammatory response is involved in
      neurodegenerative disease. In this context, we have developed an animal model of
      dopaminergic system degeneration by the intranigral injection of
      lipopolysaccharide (LPS), a potent inductor of inflammation. To address the
      importance of the inflammatory response in the LPS-induced degeneration of nigral
      dopaminergic neurones, we carried out two different kinds of studies: (i) the
      possible protective effect of an anti-inflammatory compound, and (ii) the effect
      of the intranigral injection of inflammatory cytokines (TNF-alpha, IL-1beta and
      IFN-gamma) on dopaminergic neurones viability. Present results show that
      dexamethasone, a potent anti-inflammatory drug that interferes with many of the
      features characterizing pro-inflammatory glial activation, prevented the loss of
      catecholamine content, Tyrosine hydroxylase (TH) activity and TH immunostaining
      induced by LPS-injection and also the bulk activation of microglia/macrophages.
      Surprisingly, injection of the pro-inflammatory cytokines failed to reproduce the
      LPS effect. Taken together, our results suggest that inflammatory response is
      implicated in LPS-induced neurodegeneration. This damage may be due, at least in
      part, to a cascade of events independent of that described for TNF-alpha/IL-1
      beta/IFN-gamma.

PMID- 12067228
TI  - Synaptic regulation of somatodendritic dopamine release by glutamate and GABA
      differs between substantia nigra and ventral tegmental area.
AB  - Midbrain dopamine (DA) cells of the substantia nigra pars compacta (SNc) and the
      ventral tegmental area (VTA) exhibit somatodendritic release of DA. To address
      how somatodendritic release is regulated by synaptic glutamatergic and GABAergic
      input, we examined the effect of ionotropic-receptor antagonists on locally
      evoked extracellular DA concentration ([DA]o) in guinea pig midbrain slices.
      Evoked [DA]o was monitored with carbon-fiber microelectrodes and fast-scan cyclic
      voltammetry. In SNc, evoked [DA]o was 160% of control in the presence of the AMPA
      receptor antagonist, GYKI-52466, or the NMDA-receptor antagonist, AP5. Similar
      increases were seen with the GABAA-receptor antagonist, picrotoxin, or the
      GABA(B)-receptor antagonist, saclofen. The increase seen with GYKI-52466 was
      prevented when both picrotoxin and saclofen were present, consistent with normal,
      AMPA-receptor mediated activation of GABAergic inhibition. The increase with AP5
      persisted, however, implicating NMDA-receptor mediated activation of another
      inhibitory circuit in SNc. In the VTA, by contrast, evoked [DA]o was unaffected
      by GYKI-52466 and fell slightly with AP5. Neither picrotoxin nor saclofen alone
      or in combination had a significant effect on evoked [DA]o. When GABA receptors
      were blocked in the VTA, evoked [DA]o was decreased by 20% with either GYKI-52466
      or AP5. These data suggest that in SNc, glutamatergic input acts predominantly on
      GABAergic or other inhibitory circuits to inhibit somatodendritic DA release,
      whereas in VTA, the timing or strength of synaptic input will govern whether the
      net effect on DA release is excitatory or inhibitory.

PMID- 12067230
TI  - Overexpression of manganese superoxide dismutase attenuates neuronal death in
      human cells expressing mutant (G37R) Cu/Zn-superoxide dismutase.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      characterized by loss of motor function and eventual death as a result of
      degeneration of motor neurons in the spinal cord and brain. The discovery of
      mutations in SOD1, the gene encoding the antioxidant enzyme Cu/Zn-superoxide
      dismutase (CuZnSOD), in a subset of ALS patients has led to new insight into the
      pathophysiology of ALS. Utilizing a novel adenovirus gene delivery system, our
      laboratory has developed a human cell culture model using chemically
      differentiated neuroblastoma cells to investigate how mutations in SOD1 lead to
      neuronal death. Expression of mutant SOD1 (G37R) resulted in a time and dose
      related death of differentiated neuroblastoma cells. This cell death was
      inhibited by overexpression of the antioxidant enzyme manganese superoxide
      dismutase (MnSOD). These observations support the hypothesis that mutant SOD1
      associated neuronal death is associated with alterations in oxidative stress, and
      since MnSOD is a mitochondrial enzyme, suggest that mitochondria play a key role
      in disease pathogenesis. Our findings in this model of inhibition of mutant SOD1
      associated death by MnSOD represent an unique approach to explore the underlying
      mechanisms of mutant SOD1 cytotoxicity and can be used to identify potential
      therapeutic agents for further testing.

PMID- 12067229
TI  - NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.
AB  - NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3
      dione-3-oxime] belongs to a chemical series of compounds, which exhibit
      neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)
      differentiated PC12 cells from death induced by withdrawal of trophic factors. In
      addition, NS 1231 stimulated NGF-induced neurite outgrowth of undifferentiated
      PC12 cells. At the molecular level, NS 1231 enhanced NGF-induced signalling
      events, such as TrkA phosphorylation at the Shc-binding site Tyr490 as well as
      ERK activation in PC12 cells. Moreover, NS 1231 reduced NMDA-induced
      excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of
      transient global ischaemia, treatment with NS 1231 reduced the delayed loss of
      neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in
      a 43% reduction in total infarct volume in the mouse middle cerebral artery
      occlusion (MCAO) model. The present data thus implicate a therapeutic potential
      of NS 1231 or structural analogues in treatment of cerebral ischaemia.

PMID- 12067231
TI  - Pigment epithelium-derived factor is elevated in CSF of patients with amyotrophic
      lateral sclerosis.
AB  - Pigment epithelium-derived factor (PEDF), a recently defined retinal trophic
      factor and anti-angiogenic factor for the eye, is also present in the CNS and is
      a motor neuron protectant. We asked whether PEDF levels in CSF are altered in
      patients with amyotrophic lateral sclerosis (ALS). Pigment epithelium-derived
      factor protein was detected by quantitative western blot analysis with a PEDF
      specific antiserum. Levels of PEDF in CSF, expressed as a ratio to total CSF
      protein, were significantly elevated 3.4-fold in 15 patients with ALS compared
      with neurologic disease controls (p < 0.0003). This increase does not seem likely
      to reflect up-regulation of PEDF synthesis in muscle in response to denervation,
      as CSF PEDF was not elevated in severe denervating diseases other than ALS. Nor
      does the increase represent some non-specific release in neurodegeneration, as
      CSF PEDF was not elevated in other neurodegenerative diseases. While the
      mechanism of this presumably reactive increase is not known, the distinctive,
      surprisingly elevated level of PEDF in the CSF may be an autoprotective reaction
      in ALS.

PMID- 12067232
TI  - Sepsis inhibits reduction of dehydroascorbic acid and accumulation of ascorbate
      in astroglial cultures: intracellular ascorbate depletion increases nitric oxide
      synthase induction and glutamate uptake inhibition.
AB  - Sepsis is associated with oxidative stress and impaired glutamatergic
      transmission in brain. We investigated whether sepsis impairs accumulation of the
      antioxidant, ascorbate, and uptake of glutamate by astrocytes. Bacterial
      endotoxin (Escherichia coli lipopolysaccharide, LPS) and the inflammatory
      cytokine, interferon-gamma (IFNgamma), were applied to primary astrocyte cultures
      to model sepsis. In the absence of ascorbate, the combination of LPS and IFNgamma
      (LPS + IFNgammay) up-regulated inducible nitric oxide synthase (iNOS) and
      decreased the initial rate of glutamate uptake by 50% within 24 h. Cell viability
      and facilitated glucose transport activity were not affected at 24 h. Pre
      treatment with ascorbate-2-O-phosphate increased intracellular ascorbate
      concentration and attenuated the induction of iNOS and inhibition of glutamate
      uptake caused by LPS + IFNgamma. Subsequent experiments examined the mechanisms
      by which cells accumulate ascorbate. LPS + IFNy decreased slightly the initial
      rate of uptake of ascorbate and inhibited markedly the rate with which
      intracellular dehydroascorbic acid (DHAA) was reduced to ascorbate. We conclude
      that septic insult impairs astrocytic clearance of DHAA from the extracellular
      fluid and decreases intracellular ascorbate concentration. Furthermore, sepsis
      induces iNOS and inhibits glutamate uptake by astrocytes through mechanisms that
      can be modulated by intracellular ascorbate. These results indicate treatments
      that increase intracellular ascorbate concentration may be beneficial for
      patients at risk for neurologic complication in sepsis.

PMID- 12067233
TI  - Co-administration of IGF-I and glycosaminoglycans greatly delays motor neurone
      disease and affects IGF-I expression in the wobbler mouse: a long-term study.
AB  - The study on wobbler mouse has shown that the combined treatment with low doses
      of glycosaminoglycans (GAGs) and insulin-like growth factor-I (IGF-I) fully
      prevented motor neurone death and forelimb impairment up to 9-12 weeks of a
      mouse's life. The effect was accompanied by the prevention of the early
      hypertrophy of wobbler neurones, an effect likely due to the promotion of
      neuronal survival. At the 18th week, wobbler mice treated with IGF-I + GAGs still
      showed significantly improved forelimb function, reduced muscle atrophy and a
      higher number of cervical motor neurones. IGF-I alone and GAGs alone were active
      up to the 3rd week of treatment; thereafter the beneficial effects of single
      treatments decreased drastically. GAGs and IGF-I treatments also affected IGF-I
      plasma and muscle levels. In wobbler mice there was a progressive reduction in
      IGF-I plasma levels that was prevented by IGF-I or GAGs alone and greatly
      increased, even above heterozygote levels, by the combination treatment. Such a
      powerful increase was correlated by a small enhancement in insulin-like growth
      factor binding protein-3 (IGFBP-3) plasma levels, while treatment with IGF-I
      alone affected very significantly both IGFBP-1 and IGFBP-3. Co-treatment also
      prevented the decrease in IGF-I content observed in vehicle-treated wobbler mice
      forelimb muscles.

PMID- 12067234
TI  - Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier.
AB  - The blood-brain barrier (BBB) restricts transport of immunoglobulin G (IgG) in
      the blood to brain direction. However, IgG undergoes rapid efflux in the brain to
      blood direction via reverse transcytosis across the BBB after direct
      intracerebral injection. This BBB IgG transport system has the characteristics of
      an Fc receptor (FcR), but there is no molecular information on the putative BBB
      FcR. The present study uses confocal microscopy and an antibody to the rat
      neonatal FcR (FcRn), and demonstrates the expression of the FcRn at the brain
      microvasculature and choroid plexus epithelium. Co-localization with the Glut1
      glucose transporter indicates the brain microvascular FcRn is expressed in the
      capillary endothelium. The capillary endothelial FcRn may mediate the 'reverse
      transcytosis' of IgG in the brain to blood direction.

PMID- 12067235
TI  - Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral
      ischemia.
AB  - Caspase family genes play a critical role in the initiation and execution of
      programmed cell death. Programmed cell death is an important contributor to
      neuronal loss following cerebral ischemia. We have performed a series of
      experiments to investigate the role of a specific caspase, caspase-2, in the
      development of delayed neuronal death following transient global ischemia in the
      rat. A rat ischemic brain cDNA library was screened, and two splice-variants of
      caspase-2 mRNA were identified, caspase-2S and caspase-2L, which were highly
      homologous with the sequences of human and mouse caspase-2S and caspase-2L genes,
      respectively. RT-PCR demonstrated an increase in expression of both caspase-2S
      and caspase-2L mRNA at 8, 24 and 72 h of reperfusion after global ischemia. The
      ratio of the two PCR fragments did not change significantly throughout the time
      course of reperfusion. Western blot with monoclonal antibody specific to the pro
      apoptotic caspase-2L splice variant revealed an increase in procaspase-2 (51 kDa)
      protein from 4 to 72 h following ischemia compared with sham-operated controls.
      Furthermore, an approximately 30-kDa cleavage product appeared at 8 h and
      increased with increasing duration of reperfusion. Thus, caspase-2L is both
      translated and activated following transient global ischemia. Finally,
      intraventricular administration of the caspase-2-like inhibitor (VDVAD-FMK) 30
      min before induction of ischemia decreased the number of CA1 neurons staining
      positively for DNA damage (Klenow-labeling assay) and increased the number of
      healthy-appearing CA1 neurons (cresyl violet) compared with vehicle-treated
      controls. Taken together, the data suggest that caspase-2 induction and
      activation are important mediators of delayed neuronal death following transient
      global ischemia.

PMID- 12067236
TI  - Identification and characterization of a novel Nogo-interacting mitochondrial
      protein (NIMP).
AB  - Nogo is a potent inhibitor of regeneration following spinal cord injury. To
      develop a better understanding of the mechanisms responsible for regenerative
      failure we used a yeast two-hybrid approach to try and identify proteins that
      interact with Nogo. We identified a novel mitochondrial protein designated Nogo
      interacting mitochondrial protein (NIMP) in a screen of an adult human brain cDNA
      library. This interaction was confirmed by co-immunoprecipitation in both brain
      tissue (endogenous) and transfected HEK293T cells (overexpressed). In support of
      these studies we demonstrate that Nogo interacts with the UQCRC1 and UQCRC2
      components of complex III, within the mitochondrial respiratory chain. The
      mitochondrial localization of NIMP was evidenced by confocal image analysis and
      western blot analysis of isolated mitochondria. NIMP is highly conserved and
      ubiquitously expressed in mitochondria-enriched tissues. Within the CNS, NIMP
      like immunoreactivity is present in neurons and astrocytes. These data suggest
      that NIMP is a novel mitochondrial protein that interacts with Nogo. The
      interaction of Nogo with mitochondrial proteins may provide insight into the
      mechanisms for Nogo-induced inhibition of neurite growth.

PMID- 12067237
TI  - The role of dopamine in motor symptoms in the R6/2 transgenic mouse model of
      Huntington's disease.
AB  - In both Huntington's disease (HD) patients and genetic mouse models of HD, there
      is a pre-symptomatic loss of dopamine (DA) receptors, suggesting that
      dysfunctional dopaminergic neurotransmission may be involved in early HD
      presentation. However, the role of DA in HD symptoms is not fully understood. In
      this study, we examined the possibility that dysfunctional dopaminergic
      neurotransmission contributes to the progressive decline in motor function of a
      transgenic mouse model of HD (R6/2 line). We found that R6/2 mice display an age
      dependent abnormal behavioural response to (+)-methamphetamine (METH) and a dose
      dependent increase in sensitivity to METH toxicity compared with wild-type (WT)
      mice. R6/2 mice also showed an attenuated response to cocaine, indicating that DA
      release may be compromised. Striatal DA levels were reduced in R6/2 mice by 9
      weeks of age. Replacement of DA by chronic treatment with laevodopa (L-DOPA,
      administered as Sinemet) caused short-term improvements in activity and rearing
      behaviour, and abolished abnormal spontaneous hindlimb grooming. However, long
      term treatment with L-DOPA had deleterious effects on survival and rotarod
      performance of R6/2 mice. These results suggest that dysfunctional DA
      neurotransmission contributes to phenotype development in R6/2 mice and thus also
      may be important in symptom progression in HD.

PMID- 12067238
TI  - Selective zif268 mRNA induction in the perirhinal cortex of macaque monkeys
      during formation of visual pair-association memory.
AB  - To elucidate the molecular basis of cognitive memory formation in the primate,
      transcriptional activation during learning of a visual pair-association (PA) task
      was evaluated systematically along the occipito-temporo-hippocampal pathway in
      the macaque monkey brain. Split-brain monkeys were used for intra-animal
      comparison, which enables elimination of animal-to-animal variation in gene
      expression. We found that the expression of the mRNA of an immediate-early gene
      (IEG), zif268, was up-regulated selectively in the perirhinal cortex (area 36)
      during the formation of PA memory compared to that during learning of a visual
      control task. The mRNA expression levels of another IEG, c-jun, were not up
      regulated during the PA learning in any cortical areas examined. We also showed
      that cells strongly expressing zif268 mRNA accumulated in patches in area 36
      during learning of the PA task. As the zif268 gene encodes a transcription
      factor, these results suggest that the activation of zif268 mRNA in area 36 may
      function as a trigger of the cascade of gene activation that leads to cellular
      events underlying neuronal reorganization for visual long-term memory formation.

PMID- 12067239
TI  - Focal neurometabolic alterations in mice deficient for succinate semialdehyde
      dehydrogenase.
AB  - Metabolite profiling in succinate semialdehyde dehydrogenase (SSADH; Aldh5a1-/-)
      deficient mice previously revealed elevated gamma-hydroxybutyrate (GHB) and total
      GABA in urine and total brain and liver extracts. In this study, we extend our
      metabolic characterization of these mutant mice by documenting elevated GHB and
      total GABA in homogenates of mutant kidney, pancreas and heart. We quantified
      beta-alanine (a GABA homolog and putative neurotransmitter) to address its
      potential role in pathophysiology. We found normal levels of beta-alanine in
      urine and total homogenates of mutant brain, heart and pancreas, but elevated
      concentrations in mutant kidney and liver extracts. Amino acid analysis in mutant
      total brain homogenates revealed no abnormalities except for significantly
      decreased glutamine, which was normal in mutant liver and kidney extracts.
      Regional amino acid analysis (frontal cortex, parietal cortex, hippocampus and
      cerebellum) in mutant mice confirmed glutamine results. Glutamine synthetase
      protein and mRNA levels in homogenates of mutant mouse brain were normal. We
      profiled organic acid patterns in mutant brain homogenates to assess brain
      oxidative metabolism and found normal concentrations of Kreb's cycle
      intermediates but increased 4,5-dihydroxyhexanoic acid (a postulated derivative
      of succinic semialdehyde) levels. We conclude that SSADH-deficient mice represent
      a valid metabolic model of human SSADH deficiency, manifesting focal
      neurometabolic abnormalities which could provide key insights into
      pathophysiologic mechanisms.

PMID- 12067240
TI  - Quantitative dual-probe microdialysis: evaluation of [3H]mannitol diffusion in
      agar and rat striatum.
AB  - Dual-probe microdialysis was used to study interstitial diffusion in the rat
      brain. A radiolabelled tracer, (3H]mannitol, was continuously infused at
      different concentrations via a probe acutely implanted into the striatum of an
      anaesthetized male rat or into a dilute agar gel. Samples were collected by a
      second probe placed 1 mm away from the first, and the recovered [3H]mannitol was
      measured by liquid scintillation counting. In the striatum, the delivery of
      [3H]mannitol was counteracted by its removal from the extracellular space by
      passive uptake into cells and clearance into the microcirculation, causing the
      diffusion profile to approach quasi steady-state levels within 2 h. Diffusion
      data from brain and agar were analysed using a mathematical model. The apparent
      (effective) diffusion coefficient for [3H]mannitol was D* = 2.9 x 10(-6) cm2/s,
      the effective volume fraction alpha* = 0.30 and the clearance rate constant
      kappa= 2.3 x 10(-5)/s. A tortuosity, lambda = 1.81, and penetration distance r =
      4.2 mm, were calculated. We conclude that, using dual-probe microdialysis,
      parameters reflecting geometric and dynamic tissue properties may be obtained
      using appropriate mathematical analysis. Quantitative dual-probe microdialysis
      will be valuable in characterizing interstitial diffusion and the clearance
      processes underpinning volume transmission in the brain.

PMID- 12067241
TI  - Inhibition of rho-kinase-induced myristoylated alanine-rich C kinase substrate
      (MARCKS) phosphorylation in human neuronal cells by H-1152, a novel and specific
      Rho-kinase inhibitor.
AB  - The functions of small G protein Rho-associated kinase (Rho-kinase) have been
      determined in muscle and non-muscle cells, but, particularly in neuronal cells,
      its effector(s) has not been well known. Recently, we preliminarily reported that
      Rho-kinase phosphorylates the Ser159 residue in myristoylated alanine-rich C
      kinase substrate (MARCKS) in vitro, but it remains obscure in vivo. To further
      clarify this point, we developed an isoquinolinesulfonamide derivative, H-1152,
      that is a more specific, stronger and membrane-permeable inhibitor of Rho-kinase
      with a Ki value of 1.6 nM, but poor inhibitor of other serine/threonine kinases.
      H-1152 dose-dependently inhibited the phosphorylation of MARCKS in human
      neuroteratoma (NT-2) cells stimulated by Rho-activator lysophosphatidic acid
      (LPA), which was determined by phosphorylation site-specific antibody against
      phospho-Ser159 in MARCKS, whereas it hardly inhibited the phosphorylation
      stimulated by phorbol-12,13-dibutyrate (PDBu). In contrast, two other Rho-kinase
      inhibitors, HA-1077 at 30 microM and Y-27632 at 10-30 microM, inhibited the
      phosphorylation of MARCKS in the cells stimulated by LPA and PDBu. A PKC
      inhibitor Ro-31-8220 selectively inhibited PDBu-induced phosphorylation of
      MARCKS. Taken together with our previous results, the present findings strongly
      suggest that Rho/Rho-kinase phosphorylates MARCKS at Ser159 residue in neuronal
      cells in response to LPA stimulation and that H-1152 is a useful tool to confirm
      Rho-kinase function(s) in cells and tissues.

PMID- 12067242
TI  - Quantitative dual-probe microdialysis: mathematical model and analysis.
AB  - Steady-state microdialysis is a widely used technique to monitor the
      concentration changes and distributions of substances in tissues. To obtain more
      information about brain tissue properties from microdialysis, a dual-probe
      approach was applied to infuse and sample the radiotracer, [3H]mannitol,
      simultaneously both in agar gel and in the rat striatum. Because the molecules
      released by one probe and collected by the other must diffuse through the
      interstitial space, the concentration profile exhibits dynamic behavior that
      permits the assessment of the diffusion characteristics in the brain
      extracellular space and the clearance characteristics. In this paper a
      mathematical model for dual-probe microdialysis was developed to study brain
      interstitial diffusion and clearance processes. Theoretical expressions for the
      spatial distribution of the infused tracer in the brain extracellular space and
      the temporal concentration at the probe outlet were derived. A fitting program
      was developed using the simplex algorithm, which finds local minima of the
      standard deviations between experiments and theory by adjusting the relevant
      parameters. The theoretical curves accurately fitted the experimental data and
      generated realistic diffusion parameters, implying that the mathematical model is
      capable of predicting the interstitial diffusion behavior of [3H]mannitol and
      that it will be a valuable quantitative tool in dual-probe microdialysis.

PMID- 12067243
TI  - Rapid internal acyl migration and protein binding of synthetic probenecid
      glucuronides.
AB  - Internal acyl migration reactions of drug 1-O-acyl-beta-D-glucopyranuronates
      (1beta-acyl glucuronides) are of interest because of their possible role in
      covalent binding to proteins and consequent adverse effects. The reactivity of
      the synthetic probenecid 1beta-acyl glucuronide (PRG), the principal metabolite
      of probenecid (PR) in humans, has been investigated in terms of acyl migration,
      hydrolysis, and covalent binding to proteins in phosphate buffer (pH 7.4) and
      human plasma at 37 degrees C. PRG primarily degraded by acyl migration according
      to apparent first-order kinetics and the 2-, 3-, and 4-acyl isomers sequentially
      appeared as both alpha- and beta-anomeric forms. In addition, small amounts of
      PRG and extremely labile 1alpha-acyl isomer existed in the equilibrated mixture
      favoring the 2alpha/beta-acyl isomer, that provided significant information
      regarding the mechanism of acyl migration. All of the positional isomers and
      anomers were characterized using preparative HPLC and NMR spectroscopy. Acyl
      migration was observed to predominate over hydrolysis in both media although the
      extent of hydrolysis in plasma was larger than that in the buffer. The overall
      degradation half-lives (h) in the buffer and plasma were 0.27 +/- 0.003 and 0.17
      +/- 0.007, respectively. The covalent binding rapidly proceeded mainly via the
      Schiff's base mechanism and reached a plateau after 2 h of incubation. The
      maximal binding was 146 +/- 4.8 pmol/mg of protein, and ca. 10% of the initial
      concentration of PRG. These results indicated that PRG is most labile and
      susceptible to acyl migration of all the drug acyl glucuronides reported to date
      in the physiological conditions, and highly reactive to plasma proteins, that
      could provide a possible explanation for the immunologically based adverse
      effects of PR.

PMID- 12067244
TI  - Evidence for phosphate adducts in DNA from mice treated with 4-(N-Methyl-N
      nitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
AB  - The weakly alkylating capacity of phosphotriesters (PTE) has been used for the
      determination of adducts to phosphate groups in DNA by specific transfer to the
      strongly nucleophilic compound cob(I)alamin [Cbl(I)]. When enzymatically degraded
      liver DNA from mice treated with 1-(N-methyl-N-nitrosamino)-4-(3-[3H]pyridyl)-4
      oxobutane ([3H]NNK) was added to Cbl(I), a 4-(3-[3H]pyridyl)-4-hydroxy-1-butyl
      cobalamin ([3H]PHB-Cbl) complex was formed and determined by HPLC and liquid
      scintillation counting. The PHB-Cbl formed was compared with a synthetic standard
      verified by LC/MS and 1H NMR and corresponds to phosphate adducts formed from the
      pyridyloxobutylating species from NNK and from the pyridylhydroxybutylating
      species from NNAL, NNK being to a large extent converted to NNAL in vivo. It was
      concluded that about 22% of the total level of pyridyl (oxo or hydroxy) butyl
      adducts to DNA was bound to phosphate groups.

PMID- 12067245
TI  - Reaction of aflatoxin B(1) oxidation products with lysine.
AB  - Aflatoxin (AF) B(1) exo-8,9-epoxide hydrolysis yields AFB(1) dihydrodiol, which
      undergoes base-catalyzed rearrangement to, and is in equilibrium with, AFB(1)
      dialdehyde. We investigated the reaction of AFB(1) dialdehyde with albumin to
      generate a Lys adduct, previously characterized by others [Sabbioni, G., Skipper,
      P. L., Buchi, G., and Tannenbaum, S. R. (1987) Carcinogenesis8, 819-824;
      Sabbioni, G. (1990) Chem.-Biol. Interact. 75, 1-15]. Pronase digestion of bovine
      albumin serum treated with AFB(1) dialdehyde and HPLC yielded the adduct,
      identified by its characteristic UV and mass spectra. The structure of the Lys
      AFB(1) dialdehyde adduct is concluded to be (S)-alpha-amino-2,3-dihydro-2-oxo-4
      (1,2,3,4-tetrahydro-7-hydroxy-9-methoxy-3,4-dioxocyclopenta[c][1]benzopyran-6-yl)
      1H-pyrrole-1-hexanoic acid, structure B of the former paper and 8 of the latter,
      based on work with the methylamine adduct described in the following paper in
      this issue [Guengerich, F. P., Voehler, M., Williams, K. M., Deng, Z., and
      Harris, T. M. (2002) Chem. Res. Toxicol. 15, 793-798]. The time course of product
      formation at varying concentrations of AFB(1) dialdehyde could be described by
      complexation with albumin with a K(d) of 1.5 mM and a first-order reaction rate
      with the N6-amino group of Lys of 0.033 min(-)(1). The reaction of AFB(1)
      dialdehyde with N(2)-acetylLys was monitored by UV spectroscopy and yielded a
      final spectrum similar to that of the described Lys adduct. Kinetic analysis of
      the changes at pH 7.2 was best described with a scheme involving equilibrium of
      the dialdehyde with dihydrodiol and a rate-limiting reaction of AFB(1) dialdehyde
      with the N6 atom of N(2)-acetylLys, with an apparent second-order rate constant
      of 2.6 x 10(3) M(-)(1) min(-)(1), followed by putative carbinolamine formation
      and rearrangement, collectively described by a first-order rate constant of 7.6
      min(-)(1). Competition experiments with the hydrolysis of AFB(1) exo-8,9-epoxide
      indicate that N2-acetylLys also reacts with the epoxide at pH 7.2 (k = 350 M(
      )(1) min(-)(1)) and 9.5 (k = 1.8 x 10(3) M(-)(1) min(-)(1)). This reaction might
      contribute to the formation of protein Lys adducts, depending upon the local
      concentration of free or protein Lys. Mass spectral analysis of trypsin digests
      of bovine serum albumin modified with AFB(1) dialdehyde indicated selective
      modification of Lys455 and Lys548. Collectively, these results provide more
      insight into the mechanism of formation of AFB(1) dialdehyde-protein adducts and
      indicate that the formation of Lys adducts is a moderately efficient process. The
      binding of AFB(1) dialdehyde to albumin or the protonation of the N6-amino group
      retards the reaction with Lys residues.

PMID- 12067246
TI  - Structure of the aflatoxin B(1) dialdehyde adduct formed from reaction with
      methylamine.
AB  - Amine conjugates of activated aflatoxin (AF) B(1) are formed in various systems,
      e.g., buffer amines and with protein lysine groups. Structures have been
      published in the literature, but the evidence is indirect in that (i) halogenated
      AFB(1) was usually used as the precursor and (ii) the assignment of the structure
      of the five-membered ring formed by cyclization is based on NMR chemical shifts.
      To better define these adducts and distinguish among several possibilities, we
      synthesized AFB(1) dialdehyde and reacted this with the surrogate methylamine at
      neutral pH, to simplify the system. The isolated product had the expected
      molecular ion (mass spectrometry) and showed pH-dependent UV spectra similar to
      those published for a lysine conjugate. Nuclear Overhauser enhanced spectroscopy
      (two-dimensional NMR, 800 MHz) of the sample (2H(2)O) showed proximity of the N
      CH(3) protons only with a singlet at delta 4.10, assigned to the methylene of the
      added five-membered ring, but not to a delta 6.53 singlet assigned as the vinylic
      proton of that ring. All protons in the coumarin-furanone portion of the system
      were correlated to each other but not to those in the added five-membered ring.
      These experiments establish the structure as 2,3-dihydro-2-oxo-4-(1,2,3,4
      tetrahydro-7-hydroxy-9-methoxy-3,4-dioxocyclopenta[c][1]benzopyran-6-yl)-1H
      pyrrole-1-methane. The similarity of the reaction to that occurring in the
      reaction of AFB(1) dialdehyde with lysine and the agreement of the UV spectra
      suggest that this structure is applicable for the lysine analogue. The NMR
      results support the possible structure B of Sabbioni et al. [Sabbioni, G.,
      Skipper, P. L., Buchi, G., and Tannenbaum, S. R. (1987) Carcinogenesis 8, 819
      824] and the proposed structure 8 of Sabbioni [Sabbioni, G. (1990) Chem.-Biol.
      Interact. 75, 1-15] but not alternative proposals. Kinetic and mechanistic
      considerations of the reaction of lysine with AFB(1) dialdehyde are presented in
      the previous article in this issue [Guengerich, F. P., Arneson, K. O., Williams,
      K. M., Deng, Z., and Harris, T. M. (2002) Chem. Res. Toxicol. 15, 780-793].

PMID- 12067247
TI  - Sequence mapping of epoxide adducts in human hemoglobin with LC-tandem MS and the
      SALSA algorithm.
AB  - The rapid development and integration of liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) has enabled the high-throughput identification of
      proteins and driven the expanding field of proteomics. LC-MS-MS also offers an
      attractive general approach to the analysis of xenobiotic adducts on proteins.
      The aim of this study was to examine the combined use of LC-MS-MS and the SALSA
      algorithm as a general approach to map xenobiotic adducts on proteins at the
      level of amino acid sequence. Hemoglobin (Hb) adducts are commonly used as
      biomarkers for exposure to environmental toxicants. Human Hb was incubated with
      styrene oxide, ethylene oxide, and butadiene dioxide (40 mM) to form adducts,
      digested with trypsin and analyzed by LC-MS-MS on a ThermoFinnigan LCQ ion trap
      MS instrument. Data-dependent scanning was used for acquisition of MS-MS spectra.
      The SALSA algorithm was used to detect MS-MS spectra of native and modified Hb
      peptides. The adducted sites identified are the N-terminal valines of both
      Hbalpha and Hbbeta, glutamic acid 7, cysteine 93, and histidines 77, 97, and 143
      of the beta chain and histidine 45 of the alpha chain. Specific shifts in the b-
      and y-ion series in MS-MS spectra confirmed the locations of each adduct. This
      approach offers a means to simultaneously identify multiple Hb adducts resulting
      from exposures to known or unknown toxicants. Combined application of LC-MS-MS
      and SALSA thus provides a general means of mapping protein modifications at the
      level of amino acid sequence.

PMID- 12067249
TI  - Interaction between human serum albumin and the felbamate metabolites 4-Hydroxy-5
      phenyl-[1,3]oxazinan-2-one and 2-phenylpropenal.
AB  - Felbamate is an anti-epileptic drug associated with hepatotoxicity and aplastic
      anemia. These toxicities are believed to be mediated by the formation of the
      reactive species 2-phenylpropenal. 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one is a
      metabolic precursor for 2-phenylpropenal. 4-Hydroxy-5-phenyl-[1,3]oxazinan-2-one
      exists in equilibrium with 3-oxo-2-phenylpropyl carbamate, which can undergo beta
      elimination to form 2-phenylpropenal. The work presented here investigates the
      interaction between 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one and human serum
      albumin (HSA). HSA (40 mg/mL) was found to decrease the half-life of 4-hydroxy-5
      phenyl-[1,3]oxazinan-2-one from 4.57 +/- 0.44 h to 1.07 +/- 0.10 h at pH 7.4.
      This decrease in the half-life of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one was due
      to increased beta-elimination of 3-oxo-2-phenylpropyl carbamate, presumably
      through HSA-mediated general base catalysis. The k(cat) for HSA-catalyzed
      decomposition of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one was determined to be
      12.04 min(-)(1) M(-)(1). Competitive binding assays using warfarin and ibuprofen
      showed that HSA-catalyzed decomposition of 4-hydroxy-5-phenyl-[1,3]oxazinan-2-one
      is dependent on the subdomain IIA binding site of HSA. LC/MS/MS analyses of
      trypsin digests of HSA incubations with either 4-hydroxy-5-phenyl-[1,3]oxazinan-2
      one or 2-phenylpropenal identified HSA-2-phenylpropenal adducts formed
      specifically at residues His-242 and His-247. These HSA-2-phenylpropenal adducts
      were found to be slowly reversible, with a decrease in alkylation of 74.0 +/-
      0.6% after extensive dialysis. Interestingly, only the bis-adduct (His-242 and
      His-247) could be identified after dialysis. These results demonstrate the first
      direct example of 2-phenylpropenal conjugation to a human protein in vitro and
      suggest the possibility that HSA may be involved in the development of felbamate
      toxicity either by antigen formation or as a route of detoxification of 2
      phenylpropenal.

PMID- 12067248
TI  - 7-Benzyloxyquinoline oxidation by P450eryF A245T: finding of a new fluorescent
      substrate probe.
AB  - The main objective of the present study was to find a fluorescent substrate probe
      for cytochrome P450eryF (P450eryF). P450eryF is a bacterial P450 that catalyzes
      the hydroxylation of 6-deoxyerythronolide B at the 6S position, a necessary step
      in the biosynthesis of erythromycin. The lack of a conserved threonine residue in
      the I-helix, in contrast to other P450s, makes P450eryF unable to oxidize other
      substrates. A recent study [Xiang et al. (2000) J. Biol. Chem. 275, 35999-36006]
      has shown that the substitution of Ala-245 by threonine confers on P450eryF
      significant testosterone hydroxylase activity. Therefore, we investigated various
      known fluorescent P450 substrates with P450eryF wild-type as well as two mutants,
      A245S and A245T. Among the various fluorescent compounds tested, 7
      benzyloxyquinoline (7-BQ) was found to be the most suitable probe for P450eryF
      A245T, with rates of oxidation being lower for A245S and wild-type enzyme. The
      steady-state kinetics of 7-BQ oxidation by A245T are sigmoidal (V(max) = 0.71
      nmol/min/nmol, n = 2.18, and S(50) = 132 microM). alpha-Naphthoflavone (alpha
      NF), a well-known activator of CYP3A4, did not stimulate 7-BQ oxidation by A245T,
      although the S(50) value for alpha-NF binding to wild-type P450eryF was similar
      to P450 3A4. Interestingly, spectral binding studies of wild-type P450eryF and
      A245T with ketoconazole and miconazole showed differential binding behaviors.
      Titration of wild-type with ketoconazole and miconazole and of A245T with
      miconazole showed the expected type-II binding. However, titration of A245T with
      ketoconazole produced a spectrum similar to type-I. Inhibition studies showed
      that both ketoconazole and miconazole are able to inhibit 7-BQ oxidation by
      A245T, although miconazole showed a slightly higher potency. In brief, the
      present study reports the discovery of 7-BQ as the first fluorescent and only the
      second unnatural substrate, and of miconazole as an effective P450eryF inhibitor.

PMID- 12067250
TI  - Catalytic activities of human alpha class glutathione transferases toward
      carcinogenic dibenzo[a,l]pyrene diol epoxides.
AB  - In this study, human glutathione transferases (GSTs) of alpha class have been
      assayed with the ultimate carcinogenic (-)-anti- and (+)-syn-diol epoxides (DEs)
      derived from the nonplanar dibenzo[a,l]pyrene (DBPDE) and the (+)-anti-diol
      epoxide of the planar benzo[a]pyrene [(+)-anti-BPDE] in the presence of
      glutathione (GSH). In all DEs, the benzylic oxirane carbon reacting with GSH,
      possess R-absolute configuration. GSTA1-1 demonstrated activity with all DEs
      tested whereas A2-2 and A3-3 only were active with the DBPDE enantiomers. With
      GSTA4-4, no detectable activity was observed. GSTA1-1 was found to be the most
      efficient enzyme and demonstrated a catalytic efficiency (k(cat)/K(m)) of 464 mM(
      )(1) s(-)(1) with (+)-syn-DBPDE. This activity was about 7-fold higher than that
      observed with (-)-anti-DBPDE and more than 65-fold higher than previously
      observed with less complex fjord-region DEs. GSTA3-3 also demonstrated high
      k(cat)/K(m) with the DEs of DBP and a high preference for the (+)-syn-DBPDE
      enantiomer [190 vs 16.2 mM(-)(1) s(-)(1) for (-)-anti-DBPDE]. Lowest k(cat)/K(m)
      value of the active enzymes was observed with GSTA2-2. In this case, 30.4 mM(
      )(1) s(-)(1) was estimated for (+)-syn-DBPDE and 3.4 mM(-)(1) s(-)(1) with (-)
      anti-DBPDE. Comparing the activity of the alpha class GSTs with (-)-anti-DBPDE
      and (+)-anti-BPDE revealed that GSTA1-1 was considerable more active with the
      former substrate (about 25-fold). Molecular modeling studies showed that the H
      site of GSTA1-1 is deeper and wider than that of GSTA4-4. This is mainly due to
      the changes of Ser212-->Tyr212 and Ala216-->Val216, which cause a shallower
      active site, which cannot accommodate large substrates such as DBPDE. The higher
      activity of GSTA1-1 with (+)-syn-DBPDE relative to (-)-anti-DBPDE is explained by
      the formation of more favorable interactions between the substrate and the enzyme
      GSH complex. The presence of GSTA1-1 in significant amounts in human lung, a
      primary target tissue for PAH carcinogenesis, may be an important factor for the
      protection against the harmful action of this type of potent carcinogenic
      intermediates.

PMID- 12067251
TI  - Reactive oxygen species generated by PAH o-quinones cause change-in-function
      mutations in p53.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in tobacco smoke may cause human lung
      cancer via metabolic activation to ultimate carcinogens. p53 is one of the most
      commonly mutated tumor suppressor genes in this disease. An analysis of the p53
      mutational database shows that G to T transversions are a signature mutation of
      lung cancer. Aldo-keto reductases (AKRs) activate PAH trans-dihydrodiol proximate
      carcinogens to yield their corresponding reactive and redox-active o-quinones,
      e.g., benzo[a]pyrene-7,8-dione (BP-7,8-dione). We employed a yeast reporter
      system to determine whether PAH o-quinones or the ROS they generate cause change
      in-function mutations in p53. N-Methyl-N-nitroso-N'-nitro-guanidine, a standard
      alkylating mutagen was used as a positive control. MNNG caused a dose-dependent
      increase in mutant yeast colonies and at the highest concentrations 8-14% of the
      yeast colonies were mutated and were characterized by G:C to A:T transitions in
      the p53 DNA binding domain. Treatment of p53 cDNA with micromolar concentrations
      of (+/-)-anti-7,8-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro
      benzo[a]pyrene, (anti-BPDE, an ultimate carcinogen) or sub-micromolar
      concentrations of BP-7,8-dione in the presence of redox-cycling conditions (NADPH
      and CuCl(2)) also caused p53 mutations in a dose-dependent manner. We found that
      no mutants were observed with PAH o-quinones or NADPH alone. p53 mutagenesis by
      BP-7,8-dione was attenuated by ROS scavengers and completely abrogated by a
      combination of superoxide dismutase and catalase, indicating that both superoxide
      anion and hydroxyl radicals were the responsible mutagens. The bulk of the
      mutations detected were single-point mutations and were not random in occurrence.
      Over 46% of BP-7,8-dione-induced mutations were G:C to T:A transversions,
      consistent with the formation of 8-oxo-dGuo or its secondary oxidation products.
      In addition, 25% of these mutations were at hotspots in p53 which are known to be
      mutated in lung cancer. Together these data suggest that PAH o-quinones generate
      an endogenous mutagen (ROS) which leads to p53 inactivation. These observations
      provide an alternative route to G to T transversions that dominate in p53 in lung
      cancer.

PMID- 12067252
TI  - Site-directed mutagenesis of cytochrome P450eryF: implications for substrate
      oxidation, cooperativity, and topology of the active site.
AB  - The role of five active-site residues (Phe-78, Gly-91, Ser-171, Ile-174, and Leu
      175) has been investigated in P450eryF, the only bacterial P450 known to show
      cooperativity. The residues were selected based on two-ligand-bound P450eryF
      structures and previous mutagenesis studies of other cytochromes P450. To better
      understand the role of these residues in substrate catalysis and cooperativity,
      each mutant was generated in the wild-type and A245T background, a substitution
      that enables P450eryF to oxidize testosterone and 7-benzyloxyquinoline (7-BQ).
      Replacement of Phe-78 with tryptophan decreased cooperativity of 9
      aminophenanthrene binding, with little effect on testosterone binding or
      oxidation. Interestingly, substitution of Gly-91 with alanine or phenylalanine
      abolished the type-I spectral change elicited by testosterone and significantly
      decreased testosterone hydroxylation. However, G91A/A245T showed a 4-fold higher
      k(cat) value with 7-BQ compared with A245T. Replacement of Ser-171 with alanine
      or phenylalanine did not alter cooperativity of testosterone binding but
      significantly decreased binding affinity and oxidation of testosterone and 7-BQ.
      The only mutant that exhibited an increased testosterone binding affinity and
      increased rates of testosterone and 7-BQ oxidation was I174F. Substitution of Ile
      175 with phenylalanine decreased testosterone and 7-BQ oxidation. Reaction with
      phenyldiazene showed that P450eryF may be much more open above pyrrole ring B
      than other cytochromes P450 and indicated significant changes in active-site
      topology in some of the mutants. The study suggests a crucial role of residues
      Ser-171, Ile-174, and Leu-175, which are part of a distal ligand site, in
      addition to the proximal Gly-91 in determining the oxidative properties of
      P450eryF.

PMID- 12067253
TI  - Block of L-type Ca2+ current by beauvericin, a toxic cyclopeptide, in the NG108
      15 neuronal cell line.
AB  - The effects of beauverficin, a cyclodepsipeptide compound, on ion currents in a
      mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were investigated
      with the aid of the whole-cell voltage-clamp technique. Beauvericin (0.3-100
      microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+
      current (I(Ca,L)) in a concentration-dependent manner. Beauvericin caused no
      change in the overall shape of the current-voltage relationship of I(Ca,L). The
      IC(50) value of beauvericin-induced inhibition of I(Ca,L) was 4 microM. Neither
      gabapentin (30 microM) nor omega-conotoxin GVIA (3 microM) had effects on
      I(Ca,L). Beauvericin (30 microM) shifted the steady-state inactivation curve of
      I(Ca,L) to more negative membrane potentials by approximately -15 mV. The
      inhibitory effects of beauvericin on I(Ca,L) exhibited tonic and use-dependent
      characteristics. Beauvericin also suppressed I(Ca,L) evoked by repetitive action
      potential waveforms effectively. However, beauvericin (30 microM) had no effect
      on delayed rectifier K+ current in NG105-18 cells. Under current-clamp
      configuration, beauvericin reduced the firing frequency of action potentials.
      Therefore, this study indicates that beauvericin is a relatively specific
      inhibitor of L-type Ca2+ current in NG108-15 cells.

PMID- 12067254
TI  - Cu2+-induced isoproterenol oxidation into isoprenochrome in adult rat calcium
      tolerant cardiomyocytes.
AB  - Sustained high levels of circulating catecholamines may induce cardiotoxicity.
      There is increasing evidence that this could result from catecholamine oxidation
      into aminochromes, which is catalyzed by transition metals. In fact, it has
      already been shown that copper-induced oxidation of the beta-agonist
      isoproterenol decreases the viability of isolated cardiomyocytes. Thus, the aim
      of this work was to contribute for the clarification of the mechanisms underlying
      the toxic effects of isoproterenol, Cu2+ and their concomitant effect in isolated
      rat cardiomyocytes. Freshly isolated calcium-tolerant cardiomyocytes from adult
      rat were incubated with 1 mM isoproterenol, 20 microM Cu2+ or with both during 4
      h. Isoproterenol and its aminochrome (isoprenochrome), and reduced and oxidized
      glutathione were measured at each hour in the incubation medium and in the cells.
      The intracellular activities of the selenium-dependent glutathione peroxidase,
      glutathione reductase, and glutathione-S-transferase were determined after 4 h of
      incubation. Isoprenochrome was found in both cells and incubation medium in
      samples incubated with isoproterenol alone. However, in the isoproterenol plus
      Cu2+ samples, a greater depletion of isoproterenol accompanied by a proportional
      increase of isoprenochrome was observed. This higher ISO oxidation resulted in
      the depletion of intracellular glutathione and in the release of oxidized
      glutathione to the incubation medium. The content of total glutathione (intra-
      and extracellular) and the intracellular activity of the selenium-dependent
      glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were
      also decreased in the isoproterenol plus Cu2+ samples. These results seem to
      indicate that the oxidative stress resulting from catecholamine/transition metal
      association may contribute to catecholamine cardiotoxicity.

PMID- 12067255
TI  - Determination of the alpha-tocopherol inhibition rate constant for peroxidation
      in low-density lipoprotein.
AB  - This work reports an estimate of the inhibition rate constant (k(inh)) for alpha
      tocopherol (alpha-TOH) in low-density lipoproteins (LDL) based on cholesteryl
      linoleate hydroperoxide products formed during autoxidation of intact
      lipoproteins. The ratio of cis,trans/trans,trans product hydroperoxides was
      determined during the consumption of the antioxidant. For a reasonable
      determination of k(inh) in LDL, the pro-oxidant behavior of alpha-TOH was
      minimized by oxidizing LDL with an unsymmetrical amphiphilic azo initiator which
      significantly reduces phase-transfer mediated pro-oxidant effects of alpha-TOH.
      This initiator delivers a more constant flux of initiator radicals into LDL lipid
      regions and permits determination of alpha-TOH k(inh) in LDL. Development of a
      tocopherol-mediated peroxidation (TMP) model and analysis of cholesteryl
      linoleate hydroperoxide cis,trans/trans,trans product ratios provided an
      estimated value for the inhibition rate constant of alpha-TOH in a lipoprotein of
      k(inh) = 5.9 +/- 0.5 x 10(5) M(-)(1) s(-)(1)

PMID- 12067256
TI  - Reactivity toward thiols and cytotoxicity of 3-methylene-2-oxindoles, cytotoxins
      from indole-3-acetic acids, on activation by peroxidases.
AB  - Oxidation of indole-3-acetic acid and its derivatives by peroxidases such as that
      from horseradish produces many products, including 3-methylene-2-oxindoles. These
      have long been associated with biological activity, but their reactivity has not
      been characterized. We have previously demonstrated the potential value of
      substituted indole acetic acids and horseradish peroxidase as the basis for
      targeted cancer therapy, since the compounds are of low cytotoxicity until
      oxidized, when high cytotoxicity is observed; the combination of prodrug and
      enzyme depletes intracellular thiols. In this study, 3-methylene-2-oxindole and
      derivatives substituted in the 4-, 5-, or 6-position with methyl, F, or Cl have
      been synthesized and their reactivity toward representative thiol nucleophiles
      (glutathione, cysteine, and a cysteinyl peptide) measured using stopped-flow
      kinetic spectrophotometry. Rate constants were in the range approximately 2 x
      10(3) to 2 x 10(4) M(-)(1) s(-)(1) at pH 7.4, 25 degrees C, implying a lifetime
      of a few tens of milliseconds for these methylene oxindoles in the cellular
      environment and diffusion distances of a few micrometers. As expected, halogen
      substitution decreased the rate of production of the methylene oxindoles on
      treatment of horseradish peroxidase. The cytotoxicities of the compounds were
      measured using Chinese hamster V79 fibroblast-like cells in vitro. The halogen
      substituted derivatives were much more cytotoxic than the 5-methyl analogue or
      the parent (unsubstituted) compound, consistent with the trends in rate constant
      for reaction with the thiols. The results show that the cytotoxic response in the
      prodrug (indole acetic acid) and enzyme (horseradish peroxidase) system reflects
      the reactivity of methylene oxindoles toward nucleophiles much more than the rate
      of generation of the oxindoles, and helps explain the possible advantages of 5
      fluoroindole-3-acetic acid compared to IAA as a lead compound for investigation
      in targeted cancer therapy.

PMID- 12067258
TI  - Dissociated vertical divergence: effect of weakening all four oblique muscles on
      torsional eye movements.

PMID- 12067259
TI  - Intermittent exotropia surgery in children.

PMID- 12067260
TI  - Followups on the 25th anniversary of the postop' adjustable suture (versus
      intraoperative adjustments based on the binocular alignment under general
      anesthesia, in eye muscle surgery for strabismus.

PMID- 12067261
TI  - The interface between ophthalmology and optometric vision therapy.

PMID- 12067264
TI  - Describing Duane's (Retraction Syndrome).

PMID- 12067262
TI  - Optometric vision therapy.

PMID- 12067265
TI  - Recession and measured, graded anterior transposition of the inferior oblique
      muscles for V-pattern strabismus: outcome of 44 procedures in 22 typical
      patients.
AB  - PURPOSE: This study aimed to evaluate the efficacy of recession and graded
      anterior transposition of the inferior oblique (IO) muscle to correct or to
      reduce V-pattern strabismus and associated IO overaction. METHODS: The technique
      used was that proposed by Wright, using the temporal border and the insertion of
      the inferior rectus as the reference points to locate the new insertion. In a
      retrospective study, 51 patient histories were analyzed and from this group, 22
      patients were selected as most typical examples. Patients with hypertropias
      greater than 6 prism diopters (PD), a dissociated vertical deviation (DVD)
      greater than 8 PD or decompensated DVD were excluded. RESULTS: A total of 44 eye
      surgeries on 22 patients were analyzed. We observed favorable results
      ("statistically significant") concerning the reduction of the IO overaction or V
      incomitance. In 45.5% (20 eyes) the IO function was normalized, in 15.9% (7 eyes)
      there was a reduction to -1 (underaction) and in 34.1% (15 eyes) there was a
      reduction, but there still remained a +1 overaction. In 77.3% of the patients
      there was a "satisfactory" outcome of the V pattern, defined as a residual
      incomitance less than 10 PD. CONCLUSION: In this group of patients with V-pattern
      strabismus and IO overaction, the recession and measured, graded anterior
      transposition based on Wright's technique showed satisfactory results
      ("statistically significant") in correcting the V incomitance and normalizing or
      reducing the IO overaction.

PMID- 12067266
TI  - Superior oblique recession. An update.

PMID- 12067267
TI  - Grand rounds #66: a case of a residual left hypertropia after surgery for a
      paralysis of the inferior division of the 3rd nerve.

PMID- 12067270
TI  - A pilot study. Depth perception and near stereoacuity: is it related to academic
      performance in young children?
AB  - PURPOSE: A study of the relationship between an overall measure of visual
      function at near, specifically stereoacuity, and academic performance in
      kindergarten through second grade was conducted. METHOD: One hundred seventeen
      children (mean age = 7.33 +/-0.97 years) from a middle class, suburban,
      elementary school participated in this masked investigation. The Randot 2
      stereotest was used to measure stereoacuity at 40 cm. The relationship between
      stereoacuity and teachers' personal ratings of academic ability was analyzed
      because teachers' grades are a primary means of assessing school performance. The
      children's regular classroom teachers rated the children with respect to reading,
      mathematics, and writing ability. Children in the second grade (n = 47) were also
      rated on spelling ability. Only experienced teachers were included in the
      investigation and the validity of the teachers' rating was substantiated by
      significant correlations with standardized test scores. Teachers were masked to
      performance on the stereotest. RESULTS: Performance on the Randot was found to be
      "statistically significantly" (p=<0.05) and "medically-clinically significantly"
      related to standardized reading test scores (p=0.033) and teachers' personal
      ratings of reading (p<0.001), mathematics (p<0.001), writing (p<0.001) and
      spelling (p=0.048) ability. CONCLUSION: Good visual function at near,
      particularly good stereoacuity, is significantly correlated to academic
      performance.

PMID- 12067271
TI  - Objective improvement from base-in prisms for reading discomfort associated with
      mini-convergence insufficiency type exophoria in school children.
AB  - PURPOSE: To determine whether base-in prism glasses could diminish asthenopia,
      and improve reading abilities (speed, accuracy and comprehension). METHODS: All
      patients aged 8-18 years, from one practice, were examined and considered
      prospectively over a six month period. Ten percent (72) of these 703 patients met
      initial criteria of an exodeviation greater at near than distance and reading
      discomfort. At initial examination these 72 were asked to read orally, with and
      without base-in prisms. If the senior examiner noted they read faster and with
      fewer mistakes, and the patient reported increased reading comfort, then reading
      (only) glasses with 2 to 3 diopters base-in prism OU were prescribed. Of the 72,
      33 were so treated. After 3 weeks they were given the Gray Oral Reading Test
      (GORT-3). This test has two equal parts which were administered one with, and one
      without, prisms. A subjective questionnaire was also administered. RESULTS: The
      overall mean improvement in reading speed, accuracy and comprehension on the GORT
      3 with base-in prisms, was from the 34th to the 66th percentile. The
      improvements in reading were "statistically significant" at p<.001. Patients also
      reported subjective improvement in asthenopic symptoms and headaches. CONCLUSION:
      Base-in prism glasses improve subjective reading comfort and abilities (speed,
      accuracy and comprehension) in these patients.

PMID- 12067272
TI  - Measuring surgical skill and proclivity in ophthalmology residency training
      program applicants using the American Dental Association Dental Admission
      (Sample) Test (DAT).
AB  - PURPOSE: To determine if typical DAT perceptual ability questions which are used
      to determine potential surgical skills in dental school applicants also do so for
      surgical ability for eye surgery. METHOD: The subjects were all applicants for
      admission into the Ophthalmology Residency Training Program at the University of
      Florida. All applicants answered 11 questions from the "Perceptual Ability"
      section of the DAT. Their answers were neither reviewed nor scored at the time
      they took the test but were sealed and set aside. After completing the 3 year
      training program, each of fifteen consecutive trainees was scored by five masked
      faculty members for their surgical skill. Their tests were unsealed and scored.
      Data were obtained on 15 applicants. RESULTS: There was a [Good] positive
      correlation between masked faculty surgical skill scores and DAT scores: r=
      +0.58, p < or -0.02. CONCLUSION: DAT perceptual ability questions do indicate
      candidates with best innate and potential eye surgical skills.

PMID- 12067273
TI  - Seattle followup: did you get the metamessage of the nerd glasses?

PMID- 12067274
TI  - Inhibitor specificity of recombinant and endogenous caspase-9.
AB  - Apoptosis triggered through the intrinsic pathway by radiation and anti
      neoplastic drugs is initiated by the activation of caspase-9. To elucidate
      control mechanisms in this pathway we used a range of synthetic and natural
      reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD
      CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the
      endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein
      ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these
      compounds in a cell-free system. However, the viral proteins CrmA and p35,
      although potent inhibitors of recombinant caspase-9, had almost no ability to
      block caspase-9 in this system. These findings were also mirrored in cell
      expression studies. We hypothesize that the viral inhibitors CrmA and p35 are
      excluded from reacting productively with the natural form of active caspase-9 in
      vivo, making the potency of inhibitors highly context-dependent. This is
      supported by survival data from a mouse model of apoptosis driven by Sindbis
      virus expressing either p35 or a catalytic mutant of caspase-9. These results
      consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in
      vitro, yet fails to block caspase-9-mediated cell death.

PMID- 12067275
TI  - High expression in involuting reproductive tissues of uterocalin/24p3, a
      lipocalin and acute phase protein.
AB  - During reproduction the mass and number of cells in the uterus and the mammary
      gland increase rapidly and then diminish more rapidly after their reproductive
      functions are completed. The diminishment of tissue mass, known as involution,
      involves an ordered series of events that includes apoptosis of resident cells,
      neutrophil invasion, the release of degradative enzymes and phagocytosis of
      cellular debris. Local signals are believed to regulate the progression of
      involution in each tissue. Here we show that the mammary gland and uterus express
      high levels of uterocalin, a protein that specifically induces apoptosis in
      neutrophils and other leucocytes. In the mammary gland, uterocalin expression is
      induced by weaning. In both tissues, uterocalin is expressed at extremely high
      levels such that it constitutes an average of 0.2-0.5% of the total extractable
      protein at its peak. Epithelial cells in the uterus and mammary gland produce
      uterocalin. In each case, the protein is secreted into the tissue lumen, with
      mammary-derived uterocalin being found in the milk. The period of highest
      uterocalin expression in vivo is consistent with the hypothesis that one of its
      physiological roles is to induce apoptosis of infiltrating neutrophils and
      thereby delay the entry of neutrophils into the tissue. It is proposed that the
      role of uterocalin during involution is to provide a window of time during which
      resident cells are protected from the degradative enzymes, free radicals and
      other secreted products of activated phagocytes to allow these cells to prepare
      to survive the processes of involution.

PMID- 12067276
TI  - Comparison of automated haematology analysers for detection of apoptotic
      lymphocytes.
AB  - Automated haematology analysers can rapidly provide accurate blood cell counts
      and white blood cell differentials. In this study, we evaluated four different
      haematology analysers for the detection of apoptotic lymphocytes in peripheral
      blood: MAXM A/L Retic, H*2, Cell-Dyn 3500 and NE-8000. With the MAXM A/L Retic
      haematology analyser, the apoptotic lymphocyte cluster appeared below the
      original lymphocyte cluster on the volume/DF1, and to the right under the
      original lymphocyte cluster on the volume/DF2 scattergrams. With the H*2
      haematology analyser, the apoptotic polymorphonuclear lymphocytes produced a
      higher lobularity index on the BASO channel. With the Cell-Dyn 3500 haematology
      analyser, the apoptotic lymphocyte cluster appeared to the right side of the
      original lymphocyte cluster on the 0D/10D scattergram and to the left side of the
      polymorphonuclear cluster on the 90D/10D scattergram. With the NE-8000
      haematology analyser, the apoptotic lymphocyte cluster was not distinguishable.
      Thus, apoptotic lymphocytes are readily detected on scattergrams generated by
      selected haematology analysers.

PMID- 12067277
TI  - BCR/ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic
      myeloid leukaemia (CML).
AB  - There are two major forms of the BCR/ABL fusion gene, involving ABL exon 2, but
      including different exons of BCR gene. The transcripts b2a2 or b3a2 code for a
      p210 protein. Another fusion gene leads to the expression of an e1a2 transcript,
      which codes for a p190 protein. Another, less common fusion gene is c3a2[e19a2],
      which encodes a p230 protein. The incidence of one or the other rearrangement in
      chronic myeloid leukaemia (CML) patients varies in different reported series.
      This study was designed to determine the frequency of coexpresion of the p210,
      p190 and p230 transcripts in 250 Mexican patients with CML. We performed nested
      and multiplex reverse transcriptase polymerase chain reaction (RT-PCR) on bone
      marrow samples from adult patients and found that all cases were positive for
      some type of BCR/ABL rearrangement. In 226 (90.4%) patients it was p210, while
      the remaining 9.6% showed coexpression or one of the transcripts of
      p190/p210/p230. In 7% of patients with p210 expression there are both isoforms
      (b3a2/b2a2), presumably the result of alternative splicing. The rate of
      coexpression of the p190/p210 transcripts was 5%, which is much lower than in
      other reports. This may be due to the technical factors. These patients had high
      platelet counts, marked splenomegaly and chromosomal abnormalities in addition to
      Ph'. Other types of coexpression seen were p210/p230 and p190/p210/p230, in
      patients with high-risk clinical factors. Our study confirms the occurrence of
      coexpression of different BCR/ABL transcripts, although the rate (9.6%) was much
      lower than has been reported in other populations. This may reflect either the
      sensitivity of the detection techniques used or the possibility of genetic
      differences between the populations studied. Coexpression may be due to
      alternative splicing or to phenotypic variation, with clinical courses different
      from classical CML.

PMID- 12067278
TI  - Frequent discordance of the light-chain isotypes expressed by serum monoclonal
      components and leukaemic B-cells.
AB  - In B-cell malignancies, it is generally held that the monoclonal components (MC)
      are produced by the malignant clones. Genetic relatedness implies the concordant
      expression of light-chain (LC) isotypes in the MC and at the surface of the
      malignant lymphocytes. We reviewed a series of 91 B-cell leukaemias,
      immunophenotyped by flow cytometry in our laboratory. A serum MC had been sought
      in 75 of these patients, and had been found in 23 (31%). Biclonal serum
      components were detected in three cases. LC concordance could not be assessed in
      three cases of surface LC-null lymphocytes. Of the 23 MC studied in 20 patients,
      light-chains were discordant in 39%, mostly due to kappa MC in lambda leukaemias.
      The origin of LC discordance remains speculative. It could be due to the
      emergence of subclones with the same primal VDJ gene rearrangement or,
      alternatively, to the development of new B-cell clones escaping immune
      surveillance from deregulated T-cells.

PMID- 12067280
TI  - The lungs and platelet production.
AB  - Several studies have suggested that thrombopoiesis may occur in the lungs. To
      investigate the role of the lungs in platelet production, we measured automated
      platelet parameters in blood from the pulmonary artery and the radial artery
      (n=125) or aorta (n=26) in patients undergoing aorto-coronary bypass. No
      significant differences were found between pulmonary and radial arterial blood
      with regard to platelet count (192.132 +/- 46.250 vs. 192.004 +/- 46.294 x
      10(9)/l), mean platelet volume (11.03 +/- 1.04 vs. 11.03 +/- 1.03 fl),
      plateletcrit (0.212 +/- 0.051 vs. 0.212 +/- 0.051 x 10(-2)), platelet
      distribution width (14.48 +/- 2.16 vs. 14.47 +/- 2.08 fl) and platelet-large cell
      ratio (0.350 +/- 0.076 vs. 0.351 +/- 0.078). Similar results were obtained in
      comparisons between pulmonary arterial and aortic blood. A coefficient of linear
      correlation of 0.98 was found between the pulmonary and radial arterial and
      aortic platelet counts. These findings suggest that the platelet population
      entering the lungs was the same as the platelet population leaving them. Our
      results do not therefore support the theory of pulmonary platelet production.

PMID- 12067279
TI  - Correlation between the uptake of Tc-99m-sestaMIBI and prognostic factors in
      patients with multiple myeloma.
AB  - Technetium 99m-2-methoxyisobutil-isonitrile (Tc-99m-MIBI), also called sestaMIBI,
      has been used successfully to detect malignant tumours at diagnosis. Recently, it
      has been proposed as a safe and effective tracer in patients with multiple
      myeloma (MM). The purpose of this study was to demonstrate the value of the Tc
      99m-MIBI uptake in disease detection and to assess the correlation between the
      uptake of this scintigraphy agent and prognostic factors in newly diagnosed MM
      patients. Thirty-five untreated patients were enrolled in the study. Tc-99m-MIBI
      scanning was performed in 33 patients after intravenous injection of 7.4 MBq/kg.
      Whole-body anterior and posterior scans were obtained after 30 min, 60 min, 2 and
      4 h. The correlation between known prognostic factors of MM and the intensity of
      Tc-99m-MIBI uptake was assessed. Our results showed seven patients with an
      intensity score of I0, 12 patients with I1, eight patients with I2 and six
      patients with a score of I3. There was a positive correlation between Tc-99m-MIBI
      intensity and C-reactive protein (CRP; r=0.506, P < 0.01), erythrocyte
      sedimentation rate (ESR; r=0.368, P < 0.05), beta2- microglobulin (beta2M;
      r=0.749, P < 0.001), interleukin-6 (IL-6; r=0.823, P < 0.001), soluble
      Interleukin-6 receptor (sIL-6r; r=0.806, P < 0.001), serum calcium (r=0.578, P <
      0.001) and bone alkaline phosphatase (BAP; r=0.472, P < 0.01). An inverse
      correlation was found between Tc-99m-MIBI intensity and osteocalcin (OC) and type
      I procollagen carboxyterminal propeptide (PICP). In conclusion, the results of
      this study suggest that more extensive disease activity, as determined by high
      levels of CRP, beta2M, IL-6 and sIL-6r correlated with a higher uptake of the
      radiotracer.

PMID- 12067281
TI  - Outpatient management of DVT using low molecular weight heparin and a hospital
      outreach service.
AB  - In recent years there have been several studies comparing the efficacy and safety
      of low molecular weight (LMW) and unfractionated heparin for the treatment of
      deep venous thrombosis (DVT), showing them in the clinical trial setting to be
      equal in these regards. LMWH has the advantage of once daily subcutaneous
      injection and daily monitoring of levels is not usually required. This has led
      many centres to develop outpatient treatment strategies for these patients but
      evidence for the safety of this approach is scarce. In 1997 we developed a
      hospital outreach service for the treatment of patients with DVT and, in a
      retrospective study, have compared the outcome in 172 patients treated at home
      with 172 age, sex and thrombotic risk factor matched inpatients treated at our
      institution with unfractionated heparin. Five patients in the home treatment
      group suffered a haemorrhagic event, compared with six patients in the hospital
      group. One patient in the home treatment group had a recurrent DVT within the
      first 3 months of treatment; in the hospital-treated group, six patients had
      recurrent DVTs and nine developed pulmonary emboli. At 3 months, there were three
      deaths in the home treatment group, compared with five deaths in the hospital
      group. There was no difference in re-admission rate at 3 months: 23 in the home
      treatment group, 24 in the hospital-treated group. Average length of hospital
      stay for the home-treatment group was 2.1 days and 12 days for the hospital
      group. Warfarin control was found to be significantly better in those patients
      treated at home, and only 18% of patients treated in hospital received heparin
      according to hospital guidelines. In conclusion, outpatient management of
      patients with DVT using LMWH is as safe as hospitalization and continuous
      infusion of unfractionated heparin. The complication rate was lower in the home
      treatment group and, in particular, the incidence of recurrent thrombosis was
      significantly less in the home treatment group. In addition, warfarin control was
      better when managed by specialist nurses. Patients expressed a preference for
      home treatment.

PMID- 12067282
TI  - Evaluation of an automated latex D-dimer immunoassay in the clinical assessment
      of suspected venous thromboembolism.
AB  - Because the reliability of clinical signs in venous thromboembolism (VTE) is
      poor, a highly sensitive, non-invasive test may improve the selection of patients
      requiring further investigation. We assessed the sensitivity and negative
      predictive value of an automated D-dimer latex immunoassay (IL-Test ) in 68
      patients presenting with suspected VTE. The plasma D-dimer concentration was
      estimated and an appropriate diagnostic radiological investigation performed.
      Control values were obtained from healthy young and elderly volunteers. Using a
      cut-off value of 330 ng/ml, the assay had a sensitivity of 100% and negative
      predictive value of 100% for VTE. We conclude that the IL-Test. automated D-dimer
      assay has a suitably high sensitivity and adequate negative predictive value to
      be included in a pre-test clinical probability protocol for the evaluation of
      patients with suspected VTE.

PMID- 12067283
TI  - A case of sickle-cell erythrocytosis occurring following renal transplantation.
AB  - We present an unusual case of post-renal transplant 'erythrocytosis' in a patient
      with sickle-cell anaemia, who had developed renal failure following the effects
      of a phaeochromocytoma. Prior to transplantation, the patient had experienced
      only occasional crises. However, post-transplant, he experienced multiple and
      varied crises, associated with a significant increase in haemoglobin
      concentration. These symptoms were partially alleviated by regular venesection.

PMID- 12067284
TI  - Artefactually-normal automated platelet counts due to malaria-infected RBC.
AB  - Protein aggregates, red cell or white cell fragments are known to interfere with
      platelet counts in automated blood analysers, both by aperture impedance and
      optical technologies. When a falsely high value is suspected, interference by
      pseudo-platelet particles can be confirmed by systematic examination of stained
      blood films. The method that best avoids these sources of interference is the
      reference, immunological platelet count. We describe a case of treated malaria
      with a false normal platelet count. The blood smear revealed small red cells,
      infected by trophozoites of Plasmodium falciparum, that interfered with the
      platelet count. The Cell Dyn 4000 shows different patterns of interference by
      infected red cells in its impedance and optical counts, and thrombocytopenia was
      suspected immediately. This was confirmed by a phase-contrast microscopic
      platelet count.

PMID- 12067285
TI  - Helicobacter pylori and autoimmune neutropenia.
AB  - Recent studies have suggested a high prevalence of Helicobacter pylori infection
      in patients with immune thrombocytopenia. Eradication therapy for H. pylori led
      to an increase in platelet count in a significant number of patients. No evidence
      of lymphoproliferative disorder has been reported in any of the patients in these
      studies. We describe a patient who presented initially with autoimmune
      neutropenia but was subsequently found to have a mucosa-associated lymphoid
      tissue (MALT) lymphoma. An impressive recovery of the neutrophil count was noted
      on H. pylori eradication therapy. To our knowledge this is the first reported
      case of autoimmune neutropenia associated with H. pylori-induced MALT lymphoma.
      The relationship between lymphoproliferative disorders and autoimmunity is
      discussed.

PMID- 12067286
TI  - Low cost autologous peripheral blood stem cell transplantation performed in a
      municipal hospital for a patient with plasma cell leukaemia.
AB  - Autologous peripheral blood stem cell transplantation (PBSCT) is a costly
      procedure. In India, the cost varies from US$20000 to 25000 and most patients
      cannot afford it. Using several cost-cutting measures, we were able to treat a
      patient with plasma cell leukaemia by autologous PBSCT. A 42-year-old-male
      presented with plasma cell leukaemia. He was treated with VAD therapy, followed
      by high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF)
      for mobilization of peripheral blood stem cells. The patient was conditioned with
      high dose melphalan, followed by autologous PBSCT. The procedure was performed in
      a municipal hospital in which there was no prior experience with stem cell
      transplantation. Costs were reduced by: (i) using oral medication whenever
      possible; (ii) having a relative of the patient prepare his food under medical
      guidance; (iii) starting G-CSF on day 7 rather than on day 1; (iv) short-term
      storage of the PBSC in an ordinary refrigerator at 4 degrees C without
      cryopreservation; (v) infusing a large number of CD34+ cells, which shortened the
      time to engraftment; (vi) delegating many of the functions of a marrow transplant
      nurse to a resident physician. The cost of transplantation was thereby reduced to
      about US$ 6000, with successful engraftment by day +13. The patient remained in
      remission for 7 months, after which he relapsed and was treated with chemotherapy
      and electron beam radiation to the skin.

PMID- 12067287
TI  - Development of anti-VWF antibody in a patient with severe haemophilia A following
      the development of high-grade non-Hodgkin's lymphoma.
AB  - A 9-year-old-boy with severe haemophilia A (factor VIII < 1%) developed colicky
      abdominal pain with swelling in the left iliac fossa for 4 weeks. His LDH level
      was 1423 IU/l (normal range < 220 IU/l) and his uric acid, 6.8 mg/dl. A
      computerised tomography (CT) scan of the abdomen demonstrated a tumour of the
      terminal ileum and mild hepatosplenomegaly. Pre-operative screening for factor
      VIII inhibitor was negative. Post-operatively, the patient needed high doses of
      factor VIII to maintain haemostasis. The tumour was found to be a high-grade
      lymphoma of Burkitt's type. He recovered from his operation and chemotherapy was
      commenced. Investigations demonstrated an anti-von Willebrand factor (VWF)
      antibody. He subsequently relapsed and died of progressive disease. Development
      of anti-VWF antibody in lymphoma is well known, but development of this antibody
      in a haemophilia A patient developing lymphoma has not been reported. The present
      case shows that antibody to VWF should be considered as a possible reason for an
      increased factor VIII requirement in such patients.

PMID- 12067291
TI  - Immunopathogenesis of multiple sclerosis: MBP and beyond.

PMID- 12067292
TI  - Can intestinal helminth infections (geohelminths) affect the development and
      expression of asthma and allergic disease?

PMID- 12067293
TI  - Kinetics of changes in lymphocyte sub-populations in mouse lungs after
      intrapulmonary infection with M. bovis (Bacillus Calmette-Guerin) and identity of
      cells responsible for IFNgamma responses.
AB  - Gamma interferon (IFNgamma) plays a key role in host defense against pulmonary
      mycobacterial infections. A variety of lymphocyte subsets may participate in
      producing pulmonary IFNgamma responses, but their relative contributions after
      mycobacterial infection have not been clearly elucidated. To address this
      question, C57Bl/6 female mice were infected by intrapulmonary instillation of 2.5
      x 104 BCG (Mycobacterium bovis Bacillus Calmette-Guerin). Lymphocyte populations
      in lung interstitium were examined at different time points after the infection.
      BCG load in lungs peaked between 4 and 6 weeks post-infection and declined to
      very low levels by the 12th week of infection. Recovery of lung interstitial
      lymphocytes doubled by 4-6 weeks after infection and declined thereafter. Flow
      cytometric analysis of the lung-derived lymphocytes revealed that about 5% of the
      these cells made IFNgamma in control mice, and this baseline IFNgamma production
      involved T (CD3+NK1.1-), NK (CD3-NK1.1+) and NKT (CD3+NK1.1+) cells. As the BCG
      lung infection peaked, the total number of CD3+ T cells in the lungs increased
      threefold at 5-6 weeks post-infection. There was a marked increase (sixfold) in
      the number of T cells secreting IFNgamma 5-6 weeks post-infection. Some increase
      was also noted in the NKT cells making IFNgamma, but the numbers of NK cells
      making IFNgamma in BCG-infected lungs remained unaltered. Our results suggest
      that whereas NK and NKT cells contribute to baseline IFNgamma secretion in
      control lungs, expansion in the IFNgamma-producing T-cell population was
      essentially responsible for the augmented response seen in lungs of BCG-infected
      mice.

PMID- 12067294
TI  - Modification of bacteraemia by specific antibodies and relation with mortality in
      a pneumococcal mouse sepsis model.
AB  - The relationship between mortality and the bacteraemic profile was investigated
      in a pneumococcal (serotype 6B) sepsis BALB/c mouse model where animals received
      protection by specific hyperimmune serum. A single intraperitoneal dose of
      hyperimmune serum obtained from mice immunized with the heat-inactivated strain
      was administered (non-diluted or diluted to 1/4 or to 1/16) to 5-mice study
      groups 1 h prior to intraperitoneal inoculation with the infective inoculum (3.57
      x 108 cfu/ml). Blood cultures were performed daily over 15 days, with 8 microl of
      blood being collected from the tail vein; the samples were resuspended in Todd
      Hewitt broth containing 10% trisodium citrate and plated onto blood agar for
      colony counting. Animals included in the control group received placebo (PBS).
      Mortality was 100% in control animals within the first 48 h. Hyperimmune serum
      decreased and delayed mortality in a dose-related trend, producing 100%, 80%, 60%
      and 40% survival rates at 72, 96, 144 and 360 h, with non-diluted serum.
      Bacteraemic profiles with maximum colony counts > or =5 x 107 cfu/ml in blood
      during the follow-up period were related to > or =65% probability of death,
      regardless of the serum dilution administered.

PMID- 12067295
TI  - Requirement for TNF-Tnfrsf1 signalling for sclerosing cholangitis in mice
      chronically infected by Cryptosporidium parvum.
AB  - An increase in mRNA levels for TNF and Tnfrsf1 in the bile ducts of Tnfsf5-/
      (CD40 ligand or CD154 knockout) mice developing cholangitis following infection
      by Cryptosporidium parvum (CP) is accompanied by staining for TNFalpha in areas
      of inflammation. To determine whether TNF contributed to the bile duct damage
      seen in chronically-infected animals, we bred B6 mice with disrupted genes for
      Tnfrsf1a, Tnfrsf1b and Tnfsf5. Following CP infection, the Tnfsf5-/- Tnfrsf1a &
      1b-/- mice were spared from cholangitis, even though their intestinal and bile
      duct infection by CP persisted. Mice with disruptions of Tnfsf5, and either
      Tnfrsf1a or Tnfrsf1b, developed bile duct sclerosis similar to that seen in CD40
      and Tnfsf5 knockouts. Our data indicate that signalling through either TNF
      receptor is sufficient for the bile duct damage that follows chronic CP infection
      in mice, with disruption of the Tnfsf5 molecule.

PMID- 12067296
TI  - Differential susceptibility to acute Trypanosoma cruzi infection in BALB/c and
      C57BL/6 mice is not associated with a distinct parasite load but cytokine
      abnormalities.
AB  - Inoculation of Trypanosoma cruzi, Tulahuen strain, into C57BL/6 and BALB/c mice
      led to an acute infection characterized by marked parasitaemia, myocardial
      inflammation and thymocyte depletion. While C57BL/6 mice showed a progressive and
      lethal disease, BALB/c mice partly recovered. To characterize these murine models
      more effectively, we studied the parasite burden, serum levels of major infection
      outcome-related cytokines, the in vitro features of T. cruzi infection in
      peritoneal macrophages and the immunophenotype of thymic cells. The greater
      disease severity of T. cruzi-infected C57BL/6 mice was not linked to an increased
      parasite load, as parasitaemia, myocardial parasite nests and amastigote counts
      in peritoneal macrophages were not different from those in BALB/c mice. Cortical
      thymocyte loss was accompanied by the presence of apoptotic bodies and fragmented
      nuclear DNA, whereas fluorocytometric analysis at 17 days postinfection (p.i.)
      revealed a more pronounced loss of CD4+ CD8+ cells in C57BL/6 mice. This group
      displayed higher levels of TNF-alpha on days 14 and 21 p.i., in the presence of
      lower IL-1beta and IL-10 concentrations by days 14 and 21, and days 7 and 14
      p.i., respectively. Day-21 evaluation showed higher concentrations of nitrate and
      TNF-alpha soluble receptors in C57BL/6 mice with no differences in IFN-gamma
      levels, with respect to the BALB/c group. Increased morbidity of C57BL/6 T. cruzi
      infected mice does not seem to result from an aggravated infection but from an
      unbalanced relationship between pro- and anti-inflammatory mediators.

PMID- 12067297
TI  - Effects of CTLA4-Fc on glomerular injury in humorally-mediated glomerulonephritis
      in BALB/c mice.
AB  - The effect of cytotoxic T-lymphocyte-associated molecule 4-immunoglobulin fusion
      protein (CTLA4-Fc) on humorally-mediated glomerulonephritis was studied in
      accelerated anti-glomerular basement membrane (anti-GBM) glomerulonephritis
      induced in BALB/c mice. This strain of mice develops antibody and complement
      dependent glomerulonephritis under this protocol. Sensitized BALB/c mice
      developed high levels of circulating autologous antibody titres, intense
      glomerular deposition of mouse immunoglobulin and complement, significant
      proteinuria, renal impairment, significant glomerular necrosis and a minor
      component of crescent formation 10 days after challenge with a nephritogenic
      antigen (sheep anti-GBM globulin). Early treatment during the primary immune
      response, or continuous treatment throughout the disease with CTLA4-Fc,
      significantly suppressed mouse anti-sheep globulin antibody titres in serum, and
      immunoglobulin and complement deposition in glomeruli. The degree of glomerular
      necrosis was improved and proteinuria was reduced, particularly in the earlier
      stages of disease. Late treatment by CTLA4-Fc starting one day after challenge
      with sheep anti-mouse GBM did not affect antibody production and did not
      attenuate glomerulonephritis. The low level of crescent formation found in BALB/c
      mice developing glomerulonephritis was not prevented by the administration of
      CTLA4-Fc. These results demonstrate that CTLA4-Fc is of benefit in this model of
      glomerulonephritis by its capacity to attenuate antibody production, without
      affecting the minor degree of cell-mediated glomerular injury.

PMID- 12067298
TI  - The molecular mechanism in activation-induced cell death of an Ag-reactive B cell
      clone.
AB  - TPA-1 is a subclone of B cell hybridomas established by somatic hybridization
      using B cells of A/J mice immunized with TNP-LPS, and expresses a receptor for
      TNP on the cell membrane. The present study showed that TPA-1 was induced to
      apoptotic cell death upon treatment with TNP-BSA. Therefore, TPA-1 is considered
      to provide a good model for the study on activation-induced cell death of mature
      B cells induced by soluble antigen. TNP-BSA treatment caused the generation of a
      large amount of intracellular reactive oxygen species (ROS) of TPA-1, and the
      addition of the monovalent thiol-reactive compound: monochlorobimane (MCB)
      rescued it from apoptosis as well as the antioxidant reagent: N-acetyl-L
      cysteine. Furthermore, MCB markedly inhibited the generation of ROS and prevented
      the disruption of mitochondrial membrane potential that was induced by TNP-BSA
      treatment. In addition, it counteracted the effect of TNP-BSA on the expression
      of the Bcl-2 family, resulting in down-regulation of Bax and Bad and up
      regulation of Bcl-XL. Taken together, these results suggest strongly that
      oxidative stress of mitochondria may be involved directly in apoptotic cell death
      by engagement of antigen receptors on mature B cells with soluble antigen.

PMID- 12067299
TI  - Human proteinase 3 can inhibits LPS-mediated TNF-alpha production through CD14
      degradation: lack of influence of antineutrophil cytoplasmic antibodies.
AB  - The present study was conducted to investigate if proteinase-3 (PR3) is able to
      influence lipopolysaccharide (LPS) responses of monocytes via degradation of CD14
      and if antineutrophil cytoplasmic antibodies (ANCA) may modify this process.
      Recombinant (r) CD14 and CD14 expressed on monocytes were investigated for PR3
      mediated degradation by SDS-PAGE and FACS analysis, respectively. TNF-alpha
      production in whole blood was used to determine functional consequences of CD14
      degradation. PR3 degraded rCD14 in a dose- and time-dependent fashion. Major
      degradation products were found with apparent molecular weight of 45, 25 and 10
      kDa. Treatment of PR3 with PMSF completely abolished CD14 degradation. ANCA IgG
      did not inhibit CD14 degradation. In whole blood, addition of PR3 resulted in
      diminished CD14 expression on monocytes. In contrast, CD14 was increased in a
      subpopulation of cells that expressed major histocompatibility (MHC) class II and
      PR3, but lacked expression of CD64 and CD16. LPS mediated TNF-alpha production in
      whole blood was significantly inhibited when preincubated with PR3. This study
      demonstrates that PR3 can degrade rCD14 and that PR3 differentially affects CD14
      expression in subsets of monocytes. ANCA IgG does not play a significant role
      herein.

PMID- 12067301
TI  - CpG ODN activates NO and iNOS production in mouse macrophage cell line (RAW
      264.7).
AB  - Synthetic CpG containing oligodeoxynucleotide (CpG ODN) is recognized for its
      ability to activate cells to produce several cytokines, such as IL-12 and TNF
      alpha. In the present study we have demonstrated that CpG ODN 1826, known for its
      immunostimulatory activity in the mouse system could, by itself, induce nitric
      oxide (NO) and inducible nitric oxide synthase (iNOS) production from mouse
      macrophage cell line (RAW 264.7). Neutralizing antibody against TNF-alpha was not
      able to inhibit NO or iNOS production from the CpG ODN 1826-activated
      macrophages, suggesting that although the TNF-alpha was also produced by CpG ODN
      activated macrophages, the production of iNOS was not mediated through TNF-alpha.
      Although both CpG ODN 1826 and lipopolysaccharide (LPS) were able to stimulate NO
      and iNOS production, the exposure time required for maximum production of NO and
      iNOS for the CpG ODN 1826-activated macrophages was significantly longer than
      those activated with LPS. These results were due probably to a delay of NF-kappaB
      translocation, as indicated by the delay of IkappaBalpha degradation. Moreover,
      the fact that chloroquine abolished NO and iNOS production from the cells treated
      with CpG ODN 1826 but not from those treated with LPS suggested that the
      induction of NO and iNOS production from the cells stimulated with CpG ODN (1826)
      also required endosomal maturation/acidification.

PMID- 12067300
TI  - Potential role of phosphodiesterase 7 in human T cell function: comparative
      effects of two phosphodiesterase inhibitors.
AB  - Even though the existence of phosphodiesterase (PDE) 7 in T cells has been
      proved, the lack of a selective PDE7 inhibitor has confounded an accurate
      assessment of PDE7 function in such cells. In order to elucidate the role of PDE7
      in human T cell function, the effects of two PDE inhibitors on PDE7A activity,
      cytokine synthesis, proliferation and CD25 expression of human peripheral blood
      mononuclear cells (PBMC) were determined. Recombinant human PDE7A was obtained
      and subjected to cyclic AMP-hydrolysis assay. PBMC of Dermatophagoides farinae
      mite extract (Df)-sensitive donors were stimulated with the relevant antigen or
      an anti-CD3 monoclonal antibody (MoAb). PBMC produced IL-5 and proliferated in
      response to stimulation with Df, while stimulation with anti-CD3 MoAb induced
      CD25 expression and messenger RNA (mRNA) synthesis of IL-2, IL-4 and IL-5 in
      peripheral T cells. A PDE inhibitor, T-2585, which suppressed PDE4 isoenzyme with
      high potency (IC50 = 0.00013 microM) and PDE7A with low potency (IC50 = 1.7
      microM) inhibited cytokine synthesis, proliferation and CD25 expression in the
      dose range at which the drug suppressed PDE7A activity. A potent selective
      inhibitor of PDE4 (IC50 = 0.00031 microM), RP 73401, which did not effectively
      suppress PDE7A (IC50 > 10 microM), inhibited the Df- and anti-CD3 MoAb-stimulated
      responses only weakly, even at 10 microM. PDE7 may play a critical role in the
      regulation of human T cell function, and thereby selective PDE7 inhibitors have
      the potential to be used to treat immunological and inflammatory disorders.

PMID- 12067302
TI  - The transcriptional response of human macrophages to murabutide reflects a
      spectrum of biological effects for the synthetic immunomodulator.
AB  - The synthetic immunomodulator murabutide (MB) presents multiple biological
      activities with minimal toxicity in animals and in man. Although MB is known to
      target cells of the reticuloendothelial system and to regulate cytokine
      synthesis, the molecular mechanisms underlying several of its biological effects
      are still largely unknown. In an effort to define cellular factors implicated in
      the immunomodulatory and HIV-suppressive activities of MB, we have undertaken
      profiling the regulated expression of genes in human monocyte-derived macrophages
      (MDM) following a 6-h stimulation with this synthetic glycopeptide.
      Oligonucleotide microarray analysis was performed on RNA samples of
      differentiated MDM from four separate donors, using probe sets corresponding to
      1081 genes. We have identified, in a reproducible fashion, the enhanced
      expression of 40 genes and the inhibition of 16 others in MB-treated MDM. These
      regulated genes belonged to different families of immune mediators or their
      receptors, transcription factors and kinases, matrix proteins and their
      inhibitors, ion channels and transporters, and proteins involved in cell
      metabolic pathways. Additional verification of the regulated expression of
      selected genes was carried out using Northern blots or the quantification of
      released proteins in MDM cultures. The profile of MB-regulated genes in MDM
      provides a molecular basis for some of its previously reported biological
      activities, and reveals new set of genes targeted by the immunomodulator
      suggesting potential application in novel therapeutic indications.

PMID- 12067303
TI  - Activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB in
      tumour necrosis factor-induced eotaxin release of human eosinophils.
AB  - The CC chemokine eotaxin is a potent eosinophil-specific chemoattractant that is
      crucial for allergic inflammation. Allergen-induced tumour necrosis factor (TNF)
      has been shown to induce eotaxin synthesis in eosinophils. Nuclear factor-kappaB
      (NF-kappaB) and mitogen-activated protein kinases (MAPK) have been found to play
      an essential role for the eotaxin-mediated eosinophilia. We investigated the
      modulation of NF-kappaB and MAPK activation in TNF-induced eotaxin release of
      human eosinophils. Human blood eosinophils were purified from fresh buffy coat
      using magnetic cell sorting. NF-kappaB pathway-related genes were evaluated by
      cDNA expression array system. Degradation of IkappaBalpha and phosphorylation of
      MAPK were detected by Western blot. Activation of NF-kappaB was determined by
      electrophoretic mobility shift assay. Eotaxin released into the eosinophil
      culture medium was measured by ELISA. TNF was found to up-regulate the gene
      expression of NF-kappaB and IkappaBalpha in eosinophils. TNF-induced IkappaBalpha
      degradation was inhibited by the proteasome inhibitor N-cbz-Leu-Leu-leucinal (MG
      132) and a non-steroidal anti-inflammatory drug sodium salicylate (NaSal). Using
      EMSA, both MG-132 and NaSal were found to suppress the TNF-induced NF-kappaB
      activation in eosinophils. Furthermore, TNF was shown to induce phosphorylation
      of p38 MAPK time-dependently but not extracellular signal-regulated kinases
      (ERK). Inhibition of NF-kappaB activation and p38 MAPK activity decreased the TNF
      induced release of eotaxin from eosinophils. These results indicate that NF
      kappaB and p38 MAPK play an important role in TNF-activated signalling pathway
      regulating eotaxin release by eosinophils. They have also provided a biochemical
      basis for the potential of using specific inhibitors of NF-kappaB and p38 MAPK
      for treating allergic inflammation.

PMID- 12067304
TI  - Longitudinal study of intracellular T cell cytokine production in infants
      compared to adults.
AB  - Intracellular cytokine production in lymphocytes obtained longitudinally from 325
      healthy infants aged 2-12 months was compared with adult lymphocytes using four
      colour flow cytometry. Peripheral blood samples (180 microlitres) were stimulated
      with phorbol 12-myristate 13-acetate, ionomycin and brefeldin A to induce
      production and intracellular accumulation of cytokines. The method was validated
      by assessing reproducibility, repeatibility, ruggedness (i.e. fresh versus day
      old blood samples), precision, linearity and sensitivity. Among infants, the
      number and percentage of T lymphocytes (helper/inducer T cell subsets and
      cytotoxic/suppressor T cell subsets) producing IFN-gamma (type 1) and IL4 (type
      2) increased over the first year of life but remained significantly lower than
      levels found in adults. In both infants and adults more CD4- T cells than CD4+ T
      cells were induced to make IFN-gamma. Infant Th1/Th2 ratios revealed modest Th1
      skewed (predominant) profiles compared to adults, which were 5-10 times higher.
      Infant Tc1/Tc2 ratios revealed Tc1-skewed responses which were equal to adult
      ratios by age 12 months. At 12 months infant Th2 responses were closer to adult
      levels than were Th1 cells. Intracellular cytokine detection by flow cytometry is
      a rapid, sensitive, rugged and precise method to characterize immune status
      changes over time.

PMID- 12067305
TI  - Autoantibodies to photoreceptor membrane proteins and outer plexiform layer in
      patients with cancer-associated retinopathy.
AB  - Cancer-associated retinopathy (CAR) is a paraneoplastic syndrome that is
      characterized by degeneration of the retina as a remote effect of cancer outside
      the eye. The detection of autoantibodies associated with the retinopathy may
      precede the diagnosis of the underlying cancer. We have examined the sera of two
      patients with CAR by Western blot analysis. Autoantibodies to a 40kD antigen
      doublet and a 35 kD antigen were detected. Tissue specificity of the autoantigens
      was determined by testing several different tissues. The 40 kD antigen doublet
      was most abundant in retinal extract but was also present in lung and spleen
      extracts. The 35 kD antigen showed little tissue specificity and was present in
      all tissues tested. Fractionation of retinal proteins into water-soluble and 
      insoluble proteins revealed that the 40 kD antigen doublet was highly insoluble
      and probably represented membrane-associated proteins. Immunohistochemical
      analysis of the retina showed that the 40 kD antigens locate to the
      photoreceptors while the 35 kD antigen is located in the outer plexiform layer.

PMID- 12067306
TI  - Rotavirus infections and development of diabetes-associated autoantibodies during
      the first 2 years of life.
AB  - Rotavirus, the most common cause of childhood gastroenteritis, has been
      implicated as one of the viral triggers of diabetes-associated autoimmunity. To
      study the possible association between rotavirus infections and the development
      of diabetes-associated autoantibodies, we measured the prevalence of rotavirus
      antibodies in serum samples collected at 3-6-month intervals up to the age of 2
      years from 177 children selected from consecutive newborns because they carried
      HLA-DQB1 alleles associated with increased risk for type 1 diabetes. Twenty-nine
      of the children developed at least two of four diabetes-associated autoantibodies
      (ICA, IAA, GADA or IA-2A) during the first 2 years of life (the cases), whereas
      148 children remained autoantibody-negative matched with the cases for date of
      birth, gender, living region and HLA-DQB1 alleles. The temporal association
      between the development of the first-appearing diabetes-associated autoantibody
      and rotavirus infections was studied by analysing whether the cases had a
      diagnostic increase in rotavirus antibody titre more often during the 6-month
      period that preceded seroconversion to autoantibody positivity than the controls.
      By the age of 12 months one of the 13 case children (7%), who had a serum sample
      drawn at that age and who had developed at least one type of diabetes-associated
      autoantibodies, had experienced a rotavirus infection, while 12 of the 61 (20%)
      autoantibody-negative control children had had a rotavirus infection. By 18
      months, four of the 22 autoantibody-positive cases (18%) and 18 of the 89
      controls (20%) had rotavirus antibodies, and by the age of 24 months the
      respective numbers were five of the 27 cases (19%) and 32 of the 113 (28%)
      controls. A rotavirus infection occurred during the 6 months preceding the sample
      which was positive for an autoantibody in four of the 25 periods (16%) for which
      both necessary samples were available, while the controls had a rotavirus
      infection during 55 of the 370-such periods (15%). Accordingly, our data suggest
      that rotavirus infections are unlikely triggers of beta-cell autoimmunity in
      young children with genetic susceptibility to type 1 diabetes.

PMID- 12067307
TI  - Profiles of IFN-gamma and its regulatory cytokines (IL-12, IL-18 and IL-10) in
      peripheral blood mononuclear cells from patients with multidrug-resistant
      tuberculosis.
AB  - This study investigated the profiles of IFN-gamma and its regulatory cytokines
      (IL-12, IL-18 and IL-10) in response to a purified protein derivative (PPD)
      antigen in peripheral blood mononuclear cells (PBMC) from 18 HIV-negative
      patients with multidrug-resistant tuberculosis (MDRTB), and compared them with
      those from 19 healthy tuberculin reactors (HTR). ELISA results showed that
      following stimulation with PPD, IFN-gamma production was significantly reduced,
      whereas production of both IL-18 and IL-10 was significantly elevated in MDRTB
      patients compared with HTR. Three out of 18 patients with MDRTB of greater than 4
      years duration showed significantly elevated IL-12 p70 production, induced by in
      vitro PPD stimulation of their PBMC, when compared with data from HTR. However,
      when taken as a group, MDRTB patients were similar to HTR in their IL-12 p70
      producing capacity. IL-12 p70 protein paralleled IL-12 p40 protein expression. In
      addition, the production of IL-12 p40 was significantly correlated with IL-10 in
      all patients, but was not correlated with IFN-gamma. Neutralization of IL-10
      increased IL-12 p40 about twofold, but did not significantly alter IFN-gamma
      induction in MDRTB. IFN-gamma in MDRTB was highly correlated with
      lymphoproliferation and CD4 counts, but was not correlated with IL-12, IL-18 or
      IL-10 production. Our findings suggest that patients with MDRTB have dysregulated
      IL-12, IL-18 and IL-10 production during Mycobacterium tuberculosis infection,
      and the cytokine profiles are similar to those in patients with drug-sensitive
      advanced TB previously reported in the literature. In addition, IL-10 may not
      have a dominant role in defective IFN-gamma production in patients with MDRTB.

PMID- 12067308
TI  - Asymptomatic deficiency in the peptide transporter associated to antigen
      processing (TAP).
AB  - Human HLA class I deficiency is a rare disease which, in most of the patients
      described to date, results from a defect in subunit 1 or 2 of the peptide
      transporter associated with antigen processing (TAP). The clinical features of
      TAP deficiency include a chronic inflammation of the respiratory tract and/or
      granulomatous skin lesions. In this report, we describe two adult siblings with
      an HLA class I deficiency. One individual had only spontaneously-healing skin
      granulomatous lesions, while the second did not display any of the symptoms
      associated with HLA class I deficiency and could be considered to be healthy. We
      show that the patients display a homozygous TAP2 mutation which blocks the
      maturation of HLA class I molecules. Cell surface expression of these molecules
      is strongly reduced, but three times higher than on cells from other previously
      described TAP-deficient individuals. This higher expression results, at least in
      part, from the presence of HLA-B7 molecules which are probably empty of peptide.
      The numbers of CD8+ alphabeta T cells are almost normal in these patients. The
      anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+
      alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating
      that CD8+ alphabeta T cells can participate in anti-viral responses. This study
      shows that TAP deficiency can remain totally asymptomatic for several decades,
      and suggests that in some cases, TAP-independent immune responses provide
      efficient protection from most of the common intracellular pathogens.

PMID- 12067309
TI  - Increased expression of interleukin-13 but not interleukin-4 in CD4+ cells from
      patients with the hyper-IgE syndrome.
AB  - Hyper IgE syndrome (HIES) is a rare immunodeficiency disorder characterized
      mainly by high levels of polyclonal IgE in serum and recurrent staphylococcal
      abscesses of the skin and lungs. The raised IgE levels have led researchers to
      study the synthesis of cytokines that regulate switching of immunoglobulin
      production towards IgE such as interleukin-4 (IL-4), IL-12 and interferon-gamma
      (IFN)-gamma. However, the role of IL-13 in the disease pathogenesis has not been
      investigated extensively. In this study, we investigated intracellular expression
      of IL-4 and IL-13 in mononuclear cells and CD4+ cells isolated from patients with
      HIES and healthy controls. Cells were stained intracellularly with antibodies
      directed against IL-4 and IL-13 and analysed by flow cytometry before and after
      activation with PMA and calcium ionophore. The mean proportion of resting or
      activated IL-4 and IL-13 expressing mononuclear cells were comparable in the two
      groups as well as the proportion of IL-4 expressing CD4+ cells. In contrast, the
      mean proportion of IL-13 expressing CD4+ cells was increased significantly in
      patients with HIES in both the resting and the activated state compared to
      healthy controls. We conclude that increased expression of IL-13 in CD4+ cells
      from patients with HIES could account, at least partly, for raised IgE levels in
      those individuals.

PMID- 12067310
TI  - Diversity and dynamics of the T-cell response to MBP in DR2+ve individuals.
AB  - It is generally accepted that multiple sclerosis (MS) is mediated by autoreactive
      T cells and that myelin basic protein (MBP) is one of the target autoantigens.
      The T-cell response to MBP has been analysed extensively, largely through the use
      of T-cell lines (TCL) and T-cell clones (TCC), and to date, three immunodominant
      regions (13-32, 84-103 and 144-163) have been described. However, given that TCL
      may represent a skewed pattern of peptide reactivity, we have developed a kinetic
      response assay in which the proliferation of peripheral blood mononuclear cells
      (PBMC) from MS patients and healthy individuals was measured directly against a
      panel of peptides spanning the full length of human MBP. Furthermore, PBMC from
      each subject were tested three times over the course of 18 months. A high
      proportion of MS patients exhibited a significant response to eight MBP regions
      (1-24, 30-54, 75-99, 90-114, 105-129, 120-144, 135-159 and 150-170). TCC were
      subsequently generated from MS subjects and were used to further define the
      epitope recognized in each case. Overall, normal individuals recognized
      significantly fewer peptides. In addition, we noted that the T-cell recognition
      of any one peptide can fluctuate, appearing at one time point, regressing, and
      subsequently reappearing at a later date. This study provides new insight into
      the recognition profile and dynamics of myelin-antigen-specific T cells in MS.

PMID- 12067311
TI  - Macrophage inflammatory protein 3alpha-CC chemokine receptor 6 interactions play
      an important role in CD4+ T-cell accumulation in periodontal diseased tissue.
AB  - The regulatory role of chemokines and chemokine receptors on specific lymphocyte
      recruitment into periodontal diseased tissue is poorly characterized. We observed
      that lymphocytes infiltrating inflamed gingival tissue expressed marked levels of
      CCR6. In periodontal diseased tissue, the expression of MIP-3alpha mRNA was
      detected by RT-PCR and further, MIP-3alpha was distributed in the basal layer of
      gingival epithelial cells, microvascular endothelial cells and the areas of
      inflammatory cells as shown by immunohistochemistry. Moreover, CCR6-expressing
      cells infiltrated into periodontal diseased tissue, and the proportion of CCR6
      positive CD4+ T cells was significantly elevated in periodontal diseased tissue
      compared with peripheral blood in the same patients. Furthermore, gingival
      lymphocytes isolated from patients showed migration toward MIP-3alpha in an in
      vitro chemotaxis assay in which migration was abrogated by specific antibody to
      CCR6. Thus, these findings suggested that CCR6 and the corresponding chemokine,
      MIP-3alpha may have an important regulatory role in specific lymphocyte migration
      into inflamed periodontal tissue.

PMID- 12067312
TI  - Characterization of autoantibodies from patients with Goodpasture's disease using
      a resonant mirror biosensor.
AB  - Goodpasture's disease is characterized by the binding of IgG autoantibodies to
      the glomerular basement membrane, leading to glomerular inflammation. The
      autoantigen has been identified as the noncollagenous domain of the alpha3 chain
      of type IV collagen (alpha3(IV)NC1). We have used the IAsys resonant mirror
      biosensor to analyse the extent and affinity of binding of anti-GBM antibodies
      from sera of patients to purified alpha3(IV) NC1. alpha3(IV) NC1 monomers were
      immobilized to a carboxylate cuvette, with the simultaneous use of a control
      well. The binding of serum from patients with Goodpasture's disease (n = 12),
      normal controls (n = 14) and disease controls with vasculitis (n = 14) was
      analysed. Antibody binding was detected in sera from all patients with
      Goodpasture's disease but not from controls. IAsys measurements of binding
      correlated with antibody levels assessed by the standardized ELISA used for
      clinical assays. Both ELISA and biosensor measurements showed declining antibody
      levels in serial serum samples from treated patients; however, the biosensor
      detected antibody recrudescence when ELISA remained negative. Autoantibodies from
      patients' serum had average affinity constants (Kd) of 6.5 x 10-11M to 52.07 x 10
      10M, as determined by an inhibition assay, indicating high affinity. Sips
      analysis showed that the antibody response was relatively homogeneous (values of
      0.46-1). Biosensor techniques can therefore be used to detect and characterize
      anti-GBM antibodies in serum from patients, with high sensitivity and without
      need for antibody purification. This technique may be useful in diagnosis and
      monitoring of patients with Goodpasture's disease, and may be applicable to other
      autoantibody mediated diseases.

PMID- 12067313
TI  - The Th1/Th2 cytokine balance changes with the progress of the immunopathological
      lesion of Sjogren's syndrome.
AB  - Expression of type-1 and type-2 cytokines at the mRNA level in labial salivary
      glands (LSG) of patients with Sjogren's syndrome (SS), as reported by several
      groups, have generated conflicting results. In the present study we have directly
      examined the production of IL-4, IL-13 and IFN-gamma by lymphocytes infiltrating
      the LSG of 44 consecutive patients referred for SS evaluation. Cytokines
      production was evaluated following in vitro culture of LSG in the presence of IL
      2. IFN-gamma and IL-13 were detected in the majority of SN (24/44 and 26/44,
      respectively) while IL-4 was present in 5/44 SN. The presence of IFN-gamma was
      significantly higher in SS patients, as opposed to patients who did not fulfil
      the criteria for SS (P < 0.01). In addition, almost all cultured lymphocytes
      expressed mRNA for IFN-gamma (17/19 cultures) and IL-13 (18/19) while IL-4 mRNA
      was also expressed at high frequency (14/19 cultures). Interestingly, the IFN
      gamma mRNA copies in cultured lymphocytes correlated significantly with the
      intensity of lymphocytic infiltration as evaluated by Chisholm's score (P <
      0.01). Furthermore, RT-PCR of RNA extracted from whole LSG from 14 SS patients
      also demonstrated the presence of all cytokines in the majority of the cases and
      the prevalence of IFN-gamma in LSG with high-grade infiltration. Because IL-13
      was produced by the majority of the cultured LSG, IgE production was also
      evaluated. Interestingly, IgE was detected in 21/44 LSG culture SN and mainly in
      those biopsies that had Chisholm's score less than 0.5 (P < 0.05). We conclude
      that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2
      cytokines and that the balance between them shifts in favour of Th1 in LSG with
      high infiltration score and in patients with SS.

PMID- 12067317
TI  - The Salmonella-containing vacuole is a major site of intracellular cholesterol
      accumulation and recruits the GPI-anchored protein CD55.
AB  - Intracellular, pathogenic Salmonella typhimurium avoids phago-lysosome fusion,
      and exists within a unique vacuolar niche that resembles a late endosome. This
      model has emerged from studying the trafficking of host proteins to the
      Salmonella-containing vacuole (SCV). Very little is known about the role of major
      host lipids during infection. Here, we show using biochemical analyses as well as
      fluorescence microscopy, that intracellular infection perturbs the host sterol
      biosynthetic pathway and induces cholesterol accumulation in the SCV. Cholesterol
      accumulation is seen in both macrophages and epithelial cells: at the terminal
      stages of infection, as much as 30% of the total cellular cholesterol resides in
      the SCV. We find that accumulation of cholesterol in the SCV is linked to
      intracellular bacterial replication and may be dependent on Salmonella
      pathogenicity island 2 (SPI-2). Furthermore, the construction of a three
      dimensional space-filling model yields novel insights into the structure of the
      SCV: bacteria embedded in cholesterol-rich membranes. Finally, we show that the
      glycosylphosphatidylinositol (GPI)-anchored protein CD55 is recruited to the SCV.
      These data suggest that, in contrast to prevailing models, the SCV accumulates
      components of cholesterol-rich early endocytic pathways during intracellular
      bacterial replication.

PMID- 12067318
TI  - Bacterial infection of a model insect: Photorhabdus luminescens and Manduca
      sexta.
AB  - Invertebrates, including insects, are being developed as model systems for the
      study of bacterial virulence. However, we understand little of the interaction
      between bacteria and specific invertebrate tissues or the immune system. To
      establish an infection model for Photorhabdus, which is released directly into
      the insect blood system by its nematode symbiont, we document the number and
      location of recoverable bacteria found during infection of Manduca sexta. After
      injection into the insect larva, P. luminescens multiplies in both the midgut and
      haemolymph, only later colonizing the fat body and the remaining tissues of the
      cadaver. Bacteria persist by suppressing haemocyte-mediated phagocytosis and
      culture supernatants grown in vitro, as well as plasma from infected insects,
      suppress phagocytosis of P. luminescens. Using GFP-labelled bacteria, we show
      that colonization of the gut begins at the anterior of the midgut and proceeds
      posteriorly. Within the midgut, P. luminescens occupies a specific niche between
      the extracellular matrix and basal membrane (lamina) of the folded midgut
      epithelium. Here, the bacteria express the gut-active Toxin complex A (Tca) and
      an RTX-like metalloprotease PrtA. This close association of the bacteria with the
      gut, and the production of toxins and protease, triggers a massive programmed
      cell death of the midgut epithelium.

PMID- 12067319
TI  - Modulation of Brucella-induced macropinocytosis by lipid rafts mediates
      intracellular replication.
AB  - Intracellular replication of Brucella requires the VirB complex, which is highly
      similar to conjugative DNA transfer systems. In this study, we show that Brucella
      internalizes into macrophages by swimming on the cell surface with generalized
      membrane ruffling for several minutes, after which the bacteria are enclosed by
      macropinosomes. Lipid raft-associated molecules such as
      glycosylphosphatidylinositol (GPI)-anchored proteins, GM1 gangliosides and
      cholesterol were selectively incorporated into macropinosomes containing
      Brucella. In contrast, lysosomal glycoprotein LAMP-1 and host cell transmembrane
      protein CD44 were excluded from the macropinosomes. Removing GPI-anchored
      proteins from the macrophage surface and cholesterol sequestration markedly
      inhibited the VirB-dependent macropinocytosis and intracellular replication. Our
      results suggest that the entry route of Brucella into the macrophage determines
      the intracellular fate of the bacteria that is modulated by lipid raft
      microdomains.

PMID- 12067320
TI  - Shigella flexneri regulates tight junction-associated proteins in human
      intestinal epithelial cells.
AB  - Shigella spp. are a group of Gram-negative enteric bacilli that cause acute
      dysentery in humans. We demonstrate that Shigella flexneri has evolved the
      ability to regulate functional components of tight junctions after interaction at
      the apical and basolateral pole of model intestinal epithelia. In the regulation
      of tight junctional protein assemblies, S. flexneri can engage serotype-specific
      mechanisms, which targets not only expression, but also cellular distribution and
      membrane association of components of tight junctions. Distinct mechanisms
      resulting in the regulation of tight junction-associated proteins are initiated
      after either apical or basolateral interactions. S. flexneri serotype 2a has the
      ability to remove claudin-1 from Triton X-insoluble protein fractions upon apical
      exposure to T-84 cell monolayers. S. flexneri serotype 2a and 5, but not the non
      invasive Escherichia coli strain F-18, share the ability to regulate expression
      of ZO-1, ZO-2, E-cadherin and to dephosphorylate occludin. The disruption of
      tight junctions is dependent on direct interaction of living Shigella with
      intestinal epithelial cells and is supported by heat-stable secreted bacterial
      products. Intestinal epithelial cells have the ability to compensate in part for
      S. flexneri induced regulation of tight junction-associated proteins.

PMID- 12067321
TI  - Guidelines for the use of EEG methodology in the diagnosis of epilepsy.
      International League Against Epilepsy: commission report. Commission on European
      Affairs: Subcommission on European Guidelines.
AB  - The Commission of European Affairs of the International League Against Epilepsy
      published 'Appropriate Standards for Epilepsy Care Across Europe' which contained
      recommendations for the use of electroencephalography (EEG) in the diagnosis of
      epilepsy (Brodie et al. Epilepsia 1997; 38:1245). The need for a more specific
      basic document of EEG methodology was recognized and the Subcommission on
      European Affairs was asked to produce more detailed guidelines to be used across
      Europe recognizing the range of practices in EEG laboratories. There are many
      general guidelines published on EEG methodology but this document focuses on the
      diagnosis of epilepsy. Details from previously published guidelines are included
      in references and in an appendix. These guidelines are not meant to be used as
      minimal standards but recommendations that can be applied to all EEG laboratories
      despite variations in equipment.

PMID- 12067322
TI  - Organic psychiatric disorders after aneurysmal SAH: outcome and associations with
      age, bleeding severity, and arterial hypertension.
AB  - OBJECTIVES: The Lindqvist & Malmgren's system was used to describe the outcome of
      organic psychiatric disorders (OPDs) after aneurysmal subarachnoid hemorrhage
      (aSAH) and their associations with age, bleeding severity, and pre-existing
      arterial hypertension (preAH). MATERIAL AND METHOD: OPDs were diagnosed at 3, 6,
      and 12 months after aSAH in a prospective cohort study (n=63). Reaction level
      (RLS85), World Federation of Neurological Surgeons Committee SAH scale (WFNS),
      Fisher, and hydrocephalus grades were assessed at admission. RESULTS: At 3/6/12
      months, 60/49/38% had an Astheno-emotional disorder (AED), 4/5/5% had emotional
      motivational blunting disorder (EMD) and 19/19/16% had Korsakoffs amnestic
      disorder (KAD). AED was associated with preAH, whereas EMD/KAD, but not AED, was
      associated with a higher mean age, worse median RLS85 levels, WFNS grades, and
      Fisher grades. CONCLUSIONS: OPDs were diagnosed in 59% of the patients at 12
      months after aSAH. AED, the most common OPD, had the highest recovery rate and
      was associated with preAH. Use of organic psychiatric diagnoses for evaluation of
      outcome after aSAH and other brain injuries is encouraged.

PMID- 12067323
TI  - Prognostic significance of tumor-enhancement and angiogenesis in
      oligodendroglioma.
AB  - OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement
      on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL
      AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade
      oligodendrogliomas from patients treated by extensive resection and radiotherapy
      to determine the tumor angiogenesis index (TAI), calculated by measuring the
      immunostained endothelial surface area, in microm(2), per 1000 tumor cells.
      Preoperative CT scan was evaluated in each case, and the absence or presence of
      tumor enhancement after contrast administration was recorded. Survival was
      analyzed and statistically compared for subgroups of patients with lesions in
      which the TAI was less than or greater than 15, and for subgroups of patients
      having tumors showing presence or absence of enhancement on contrast-enhanced CT.
      RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100%
      and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients
      showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed
      enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival
      rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose
      tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing
      contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no
      enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a
      relationship between enhancement on preoperative CT scan and endothelial surface
      area in oligodendrogliomas, and suggest that this enhancement and the TAI may be
      considered angiogenesis-related factors with similar prognostic significance in
      terms of survival.

PMID- 12067324
TI  - The differences of clinical parameters between small multiple ischemic lesions
      and single lesion detected by diffusion-weighted MRI.
AB  - OBJECTIVES: The cause of small infarction is mainly considered to be intracranial
      small-vessel disease. However, it is difficult to explain the mechanism of
      multiple, acute infarctions by small-vessel disease. We examined the differences
      of clinical parameters between patients with multiple small lesions and single
      lesion detected by Diffusion-weighted MRI (DWI). MATERIAL AND METHODS: We
      reviewed the clinical records of 86 consecutive stroke patients with lacunar size
      ischemic lesions on DWI during the acute stage (within 72 h of onset). The
      subjects were 55 males and 31 females (mean age 72.4 +/- 9.9 years). Small
      multiple acute ischemic lesions were defined using the following criteria 1): the
      lesions were detectable by DWI 2), the diameter of each lesion on DWI was less
      than 1.5 cm, and 3) more than one vascular territory was involved. Included in
      the analysis were age, sex, lipoprotein (a) levels, hematocrit, atrial
      fibrillation (Af), stenosis of middle cerebral artery (MCA), internal carotid
      artery (ICA) or basilar artery stenosis detected by magnetic resonance
      angiography (MRA), National Institute of Health Stroke Scale (NIHSS) at
      admission, and a history of hypertension, diabetes mellitus, hyperlipidemia, and
      smoking. RESULTS: Twenty-one (24.4%) out of 86 patients with small acute
      infarctions had multiple acute ischemic lesions. Multiple logistic regression
      analysis showed that Af and stenosis of ICA or basilar artery were significantly
      more prevalent in patients with multiple lesions than single lesions. CONCLUSION:
      Multiple, small lesions visible in DWI are likely to be caused by emboli from
      heart or atheroma of the large vessels than single small lesion.

PMID- 12067325
TI  - The effect of age on cerebrovascular reactivity to cold pressor test and head-up
      tilt.
AB  - OBJECTIVE: To compare the cold pressor test (CPT) and head-up tilt (HUT)
      responses of the older and younger healthy individuals by transcranial Doppler.
      SUBJECTS AND METHODS: Forty healthy volunteers were divided into two age groups
      (18-39 years, 40-69 years). Mean blood velocity (v(m)) in both middle cerebral
      arteries was monitored during CPT and HUT. Mean arterial blood pressure, heart
      rate and end-tidal CO(2) (Et-CO(2)) were measured simultaneously. RESULTS: The
      v(m) increased by 7.1% during CPT and decreased by 10.1% during HUT. The v(m)
      responses were significantly lower in the older group (P < 0.01). Linear
      regression analysis showed a significant effect of age on dv(m) during both CPT
      (P < 0.01) as well as HUT (P < 0.01). CONCLUSION: The age affected the v(m)
      responses to CPT and HUT in the group of older subjects.

PMID- 12067326
TI  - Motor unit hyperexcitability in amyotrophic lateral sclerosis vs amino acids
      acting as neurotransmitters.
AB  - OBJECTIVES: Electrophysiological studies of amyotrophic lateral sclerosis (ALS)
      patients reveal not only lower motor neuron involvement, but also widespread
      signs of its hyperexcitability. They might be the consequence of changes in the
      level of amino acids acting as neurotransmitters. MATERIAL AND METHODS:
      Electrophysiological examination of 31 patients with sporadic ALS was performed.
      A hyperexcitability index (HI) was created to describe the amount of double
      discharges, fasciculation potentials or 'giant' F-waves. Glutamate, aspartate,
      glycine and GABA concentration in serum and cerebrospinal fluid (CSF) were
      estimated, using the high performance liquid chromatography technique. RESULTS:
      The electrophysiological studies revealed marked variability in HI in the
      patients group. HI did not correlate with duration of the disease and the degree
      of disability expressed with Norris score, as well as with the level of
      excitatory or inhibitory amino acids in the body fluids. CONCLUSION:
      Hyperexcitability of the motor unit observed in ALS is not directly related to
      changes in serum and CSF level of amino acids acting as neurotransmitters.

PMID- 12067327
TI  - Effect of Riluzole on serum amino acids in patients with amyotrophic lateral
      sclerosis.
AB  - OBJECTIVES: There is evidence that an imbalance between glutamatergic and
      inhibitory neurotransmission may contribute to selective neurodegeneration in
      amyotrophic lateral sclerosis (ALS). The efficacy of Riluzole in prolonging the
      survival of patients with ALS has been demonstrated in two large controlled
      trials. It is believed that Riluzole is a glutamate antagonist, but the exact
      mode of its action is not known. Data on the effects of Riluzole treatment on
      excitotoxic amino acid levels in serum are not available. MATERIAL AND METHODS:
      We prospectively studied 17 patients with ALS (diagnosed according to the El
      Escorial criteria), who received long-term treatment with Riluzole (100 mg/day).
      The subjects were evaluated at baseline (before treatment) and after 6, 12 and 18
      months on drug. Assessments included the functional status of the patients and
      serum levels of amino acids. Analysis of the serum amino acids was performed
      using high performance liquid chromatography techniques at baseline, and after 6,
      12 and 18 months of the treatment. RESULTS: At baseline, glutamate, GABA and
      total amino acid concentration in serum of the ALS patients, mainly in those with
      severe course of the disease, were increased. During the first 6 months of
      Riluzole treatment there was a significant decrease of glutamate and total amino
      acids, afterwards the values returned to the initial high values, or even an
      'overshooting' in their levels appeared. We did not observe a similar effect of
      Riluzole on glutamate and other amino acids in patients with less advanced ALS.
      CONCLUSIONS: It is suggested that the positive clinical effect of Riluzole in ALS
      patients may be related, at least partly, to its influence on amino acid
      metabolism in neural tissues.

PMID- 12067328
TI  - In vivo effect of interferon-beta 1a on interleukin-12 and TGF-beta(1) cytokines
      in patients with relapsing-remitting multiple sclerosis.
AB  - We have studied in vivo effect of interferon-beta 1a (IFN-beta 1a) (6 MIU once
      weekly i.m.) on interleukin-12 (IL-12) and transforming growth factor-beta(1)
      (TGF-beta(1)) serum levels during 6 months of therapy in group of 20 patients
      with relapsing-remitting multiple sclerosis (MS). IL-12 and TGF-beta(1)
      concentrations were measured by enzyme linked immunoabsorbent assay (ELISA).
      There was a significant increase of IL-12 levels in MS patients in comparison
      with control group, suggesting a role of this cytokine in immunity of MS. We have
      also found a significant increase of TGF-beta(1) levels after 6 months of therapy
      with IFN-beta 1a, however, there was no in vivo effect of the therapy on IL-12
      levels. The results suggest that IFN-beta 1a may exert its action through up-
      regulation and increase secretion of TGF-beta(1).

PMID- 12067329
TI  - Auditory brainstem, middle-latency, and slow cortical responses in multiple
      sclerosis.
AB  - The efficacy of auditory brainstem responses (ABRs), middle-latency responses
      (MLRs), and slow cortical potentials (SCPs) has been evaluated in 40 patients
      with multiple sclerosis (MS). ABRs and MLRs were averaged to clicks and SCPs to 1
      kHz tone bursts of 70-dB nHL intensity. ABR, MLR, and SCP abnormalities were
      detected in 65.0, 42.5, and 30.0% of the sample, respectively. The combined
      sensitivity of ABRs and MLRs amounted to 80.0%, of ABRs and SCPs to 75.0%, and of
      MLRs and SCPs to 60.0%. The joint aptitude of all three responses equalled 87.5%.
      All three responses were capable to detect MS in seven of nine patients, failing
      to display neurological signs of brainstem lesion. The responses were also
      abnormal in three of five subjects with negative magnetic resonance imaging. It
      is concluded that the combined application of ABRs, MLRs, and SCPs promotes both
      detecting and confirming MS loci.

PMID- 12067330
TI  - Anti-GM1 ganglioside antibodies in Parkinson's disease.
AB  - OBJECTIVES: To determine whether anti-GM1 antibodies are increased in Parkinson's
      disease (PD). METHODS: Serum immunoglobulin M (IgM) and IgG anti-GM1 antibodies
      were detected by enzyme-linked immunosorbent assay (ELISA) in 147 patients with
      PD and in 186 age-matched normal control subjects. Sera were assayed at initial
      dilution of 1:800 for IgM and 1:200 for IgG and were considered positive at
      absorbance values exceeding the value of 0.05 for IgM and 0.1 for IgG. RESULTS:
      Forty patients with PD (27.2%) had sera positive for IgM anti-GM1 antibodies,
      whereas only five normal controls (2.7%) resulted positive (P < 0.0001). Most of
      patients (75%) with positive sera had a tremor-dominant form of PD. Only two
      patients with PD (1.4%) and none of normal controls had sera positive for IgG
      anti-GM1 antibodies. CONCLUSION: A consistent portion of parkinsonians, mainly
      with a tremor-dominant form of PD, may have increased circulating IgM anti-GM1
      antibodies.

PMID- 12067331
TI  - Thyroid gland neurofibroma in a NF1 patient.
AB  - Neurofibromas are a hallmark of neurofibromatosis type 1 (NF1). They are usually
      benign and rarely present in the thyroid gland region. There is a suspected
      association between NF1 and intramedullary thyroid carcinoma and there is a well
      known association between NF1 and pheochromocytoma. Here, we present a 55-year
      old man with typical symptoms of NF1, whose course was complicated by a
      neurofibroma of the thyroid gland. His clinical spectrum of symptoms included
      bilateral cataract established before the age of 35 years, quadriparesis and an
      intrathoracic mass. The patient died because of abdominal carcinomatosis of
      unknown origin. The rarity of thyroid gland neurofibroma is discussed here,
      emphasizing the importance of early detection of these and other NF1
      complications, also including the risk of malignant transformation with lethal
      outcome.

PMID- 12067333
TI  - Cooperation and competition in mismatch repair: very short-patch repair and
      methyl-directed mismatch repair in Escherichia coli.
AB  - In Escherichia coli and related enteric bacteria, repair of base-base mismatches
      is performed by two overlapping biochemical processes, methyl-directed mismatch
      repair (MMR) and very short-patch (VSP) repair. While MMR repairs replication
      errors, VSP repair corrects to C*G mispairs created by 5-methylcytosine
      deamination to T. The efficiency of the two pathways changes during the bacterial
      life cycle; MMR is more efficient during exponential growth and VSP repair is
      more efficient during the stationary phase. VSP repair and MMR share two
      proteins, MutS and MutL, and although the two repair pathways are not equally
      dependent on these proteins, their dual use creates a competition within the
      cells between the repair processes. The structural and biochemical data on the
      endonuclease that initiates VSP repair, Vsr, suggest that this protein plays a
      role similar to MutH (also an endonuclease) in MMR. Biochemical and genetic
      studies of the two repair pathways have helped eliminate certain models for MMR
      and put restrictions on models that can be developed regarding either repair
      process. We review here recent information about the biochemistry of both repair
      processes and describe the balancing act performed by cells to optimize the
      competing processes during different phases of the bacterial life cycle.

PMID- 12067334
TI  - Eclipse period without sequestration in Escherichia coli.
AB  - The classical Meselson-Stahl density shift experiment was used to determine the
      length of the eclipse period in Escherichia coli, the minimum time period during
      which no new initiation is allowed from a newly replicated origin of chromosome
      replication, oriC. Populations of bacteria growing exponentially in heavy
      ((15)NH(4)+ and (13)C(6)-glucose) medium were shifted to light ((14)NH(4)+ and
      (12)C(6)-glucose) medium. The HH-, HL- and LL-DNA were separated by CsCl density
      gradient centrifugation, and their relative amounts were determined using
      radioactive gene-specific probes. The eclipse period, estimated from the kinetics
      of conversion of HH-DNA to HL- and LL-DNA, turned out to be 0.60 generation times
      for the wild-type strain. This was invariable for widely varying doubling times
      (35, 68 and 112 min) and was independent of the chromosome locus at which the
      eclipse period was measured. For strains with seqA, dam and damseqA mutants, the
      length of the eclipse period was 0.16, 0.40 and 0.32 generation times
      respectively. Thus, initiations from oriC were repressed for a considerable
      proportion of the generation time even when the sequestration function seemed to
      be severely compromised. The causal relationship between the length of the
      eclipse period and the synchrony of initiations from oriC is discussed.

PMID- 12067335
TI  - Multiple origins of hydrogenosomes: functional and phylogenetic evidence from the
      ADP/ATP carrier of the anaerobic chytrid Neocallimastix sp.
AB  - A mitochondrial-type ADP/ATP carrier (AAC) has been identified in the
      hydrogenosomes of the anaerobic chytridiomycete fungus Neocallimastix sp. L2.
      Biochemical and immunocytochemical studies revealed that this ADP/ATP carrier is
      an integral component of hydrogenosomal membranes. Expression of the
      corresponding cDNA in Escherichia coli confers the ability on the bacterial host
      to incorporate ADP at significantly higher rates than ATP--similar to isolated
      mitochondria of yeast and animals. Phylogenetic analysis of this AAC gene
      (hdgaac) confirmed with high statistical support that the hydrogenosomal ADP/ATP
      carrier of Neocallimastix sp. L2 belongs to the family of veritable mitochondrial
      type AACs. Hydrogenosome-bearing anaerobic ciliates possess clearly distinct
      mitochondrial-type AACs, whereas the potential hydrogenosomal carrier Hmp31 of
      the anaerobic flagellate Trichomonas vaginalis and its homologue from Trichomonas
      gallinae do not belong to this family of proteins. Also, phylogenetic analysis of
      genes encoding mitochondrial-type chaperonin 60 proteins (HSP 60) supports the
      conclusion that the hydrogenosomes of anaerobic chytrids and anaerobic ciliates
      had independent origins, although both of them arose from mitochondria.

PMID- 12067336
TI  - Interaction surface of the Spo0A response regulator with the Spo0E phosphatase.
AB  - Spo0A~P is the essential response regulator and transcription factor for
      sporulation initiation in Bacillus subtilis. The phosphorylation level of Spo0A
      in the cell is determined by the sensor kinase activity of the phosphorelay,
      donating phosphoryl groups, and the antagonistic effects of dephosphorylation
      mediated by the Rap and Spo0E families of phosphatases. In this study, spo0A
      mutations were generated that encoded proteins less sensitive to the activity of
      Spo0E than the wild-type protein. The Spo0A substitutions N12K, P60S, L62P and
      F88L are surface exposed and localize to the same face of the molecule as the
      active site and in its close proximity on the beta1-alpha1, beta3-alpha3 and
      beta4-alpha4 loops. The corresponding surface in the Spo0F response regulator was
      shown previously to be involved in the interaction with the RapB phosphatase, as
      well as the KinA histidine kinase and the Spo0B phosphotransferase. Thus,
      residues occupying the same position (N12:Q12, F88:Y84) and the same loops in
      Spo0A or Spo0F are involved in the interaction with the structurally unrelated
      Spo0E and RapB phosphatases, respectively, in addition to kinases and
      phosphotransferase. The specificity in phosphatase target recognition must be the
      result of side-chain variability within the response regulators and the
      interactions they promote. The residues involved in Spo0E interaction are
      identical in all Spo0A orthologues from spore-forming Bacilli encoding Spo0E
      phosphatases.

PMID- 12067337
TI  - The ShcA protein is a molecular chaperone that assists in the secretion of the
      HopPsyA effector from the type III (Hrp) protein secretion system of Pseudomonas
      syringae.
AB  - Pseudomonas syringae uses a type III protein secretion system encoded by the Hrp
      pathogenicity island (Pai) to translocate effector proteins into plant cells. One
      of these effector proteins is HopPsyA. A small open reading frame (ORF), named
      shcA, precedes the hopPsyA gene in the Hrp Pai of P. s. syringae 61. The
      predicted amino acid sequence of shcA shares general characteristics with
      chaperones used in type III protein secretion systems of animal pathogens. A
      functionally non-polar deletion of shcA in P. s. syringae 61 resulted in the loss
      of detectable HopPsyA in supernatant fractions, consistent with ShcA acting as a
      chaperone for HopPsyA. Cosmid pHIR11 carries a functional set of type III genes
      from P. s. syringae 61 and confers upon saprophytes the ability to secrete
      HopPsyA in culture and to elicit a HopPsyA-dependent hypersensitive response (HR)
      on tobacco. P. fluorescens carrying a pHIR11 derivative lacking shcA failed to
      secrete HopPsyA in culture, but maintained the ability to secrete another type
      III-secreted protein, HrpZ. This pHIR11 derivative was also greatly reduced in
      its ability to elicit an HR, indicating that the ability to translocate HopPsyA
      into plant cells was compromised. Using affinity chromatography, we showed that
      ShcA binds directly to HopPsyA and that the ShcA binding site must reside within
      the first 166 amino acids of HopPsyA. Thus, ShcA represents the first
      demonstrated chaperone used in a type III secretion system of a bacterial plant
      pathogen. We searched known P. syringae type III-related genes for neighbouring
      ORFs that shared the general characteristics of type III chaperones and
      identified five additional candidate type III chaperones. Therefore, it is likely
      that chaperones are as prevalent in bacterial plant pathogen type III systems as
      they are in their animal pathogenic counterparts.

PMID- 12067338
TI  - Two novel homologous proteins of Streptomyces coelicolor and Streptomyces
      lividans are involved in the formation of the rodlet layer and mediate attachment
      to a hydrophobic surface.
AB  - The filamentous bacteria Streptomyces coelicolor and Streptomyces lividans
      exhibit a complex life cycle. After a branched submerged mycelium has been
      established, aerial hyphae are formed that may septate to form chains of spores.
      The aerial structures possess several surface layers of unknown nature that make
      them hydrophobic, one of which is the rodlet layer. We have identified two
      homologous proteins, RdlA and RdlB, that are involved in the formation of the
      rodlet layer in both streptomycetes. The rdl genes are expressed in growing
      aerial hyphae but not in spores. Immunolocalization showed that RdlA and RdlB are
      present at surfaces of aerial structures, where they form a highly insoluble
      layer. Disruption of both rdlA and rdlB in S. coelicolor and S. lividans
      (DeltardlAB strains) did not affect the formation and differentiation of aerial
      hyphae. However, the characteristic rodlet layer was absent. Genes rdlA and rdlB
      were also expressed in submerged hyphae that were in contact with a hydrophobic
      solid. Attachment to this substratum was greatly reduced in the DeltardlAB
      strains. Sequences homologous to rdlA and rdlB occur in a number of
      streptomycetes representing the phylogenetic diversity of this group of bacteria,
      indicating a general role for these proteins in rodlet formation and attachment.

PMID- 12067339
TI  - Polymerase chain reaction-based mutageneses identify key transporters belonging
      to multigene families involved in Na+ and pH homeostasis of Synechocystis sp. PCC
      6803.
AB  - Primary ion pumps and antiporters exist as multigene families in the
      Synechocystis sp. PCC 6803 genome and show very strong homologies to those found
      in higher plants. The gene knock-outs of five putative Na+/H+ antiporters
      (slr1727, sll0273, sll0689, slr1595 and slr0415) and seven cation ATPases
      (sll1614, sll1920, slr0671-72, slr0822, slr1507-08-09, slr1728- 29 and slr1950)
      in the model cyanobacterium (http://www.kazusa.or.jp/cyano/cyano.html) were
      performed in this study relying on homologous recombination with mutagenenic
      fragments constructed using a fusion polymerase chain reaction (PCR) approach.
      The impacts of these gene knock-outs were evaluated in terms of Na+ and pH, and
      light-induced acidification and alkalization that are asso-ciated with inorganic
      carbon uptake. Two of the five putative antiporter mutants exhibit a
      characteristic interplay between the pH and Na+ dependence of growth, but only
      one of the antiporters appears to be necessary for high NaCl tolerance. On the
      other hand, the mutation of one of the two copper-trafficking ATPases produces a
      cell line that shows acute NaCl sensitivity. Additionally, disruptions of a
      putative Ca2+-ATPase and a gene cluster encoding a putative Na+-ATPase subunit
      also cause high NaCl sensitivity. The findings and possible mechanisms are
      discussed in relation to the potential roles of these transporters in
      Synechocystis sp. PCC 6803.

PMID- 12067340
TI  - Targeting and sequestration of truncated Pfs230 in an intraerythrocytic
      compartment during Plasmodium falciparum gametocytogenesis.
AB  - For malaria to be transmitted, the Plasmodium falciparum parasite must invade an
      erythrocyte and undergo gametocytogenesis. When mature intraerythrocytic
      gametocytes are taken up in a blood meal by a mosquito they emerge as gametes
      and, once fertilized, continue to differentiate into infectious sporozoites. One
      of the major proteins associated with the surface of the parasite during gamete
      differentiation is Pfs230, a 360 kDa member of a family of P. falciparum proteins
      that contains a repeated cysteine motif domain. To characterize the role of
      different regions of Pfs230, the gene was disrupted by targeted integration and
      clones isolated that expressed distinct sections of Pfs230. Independent clones
      D1.356 a and b express the first 452 amino acids (aa) of Pfs230 and do not
      contain a cysteine motif domain, whereas clones D2.850 a and b express the first
      950 aa, including the first cysteine motif domain. Although both sets of clones
      undergo gametogenesis and produce morphologically normal gametes, neither
      truncated Pfs230 is located on the surface of the gamete. In clones D1.356 a and
      b, the 452 aa Pfs230 is secreted into the parasitophorous vacuole and released as
      a soluble protein when the parasite emerges from the erythrocyte as a gamete. In
      marked contrast, the 950 aa form of Pfs230 expressed by clones D2.850 a and b is
      sequestered in a novel tubular compartment in the erythrocyte cytoplasm. This
      sexual-stage tubular intraerythrocytic compartment (STIC) is not recognized by
      antibodies specific for proteins associated with the parasitophorous vacuole
      membrane (Pfs16 or Exp-1) or Maurer's clefts (Pfsbp 1 or mAb LWL1) or
      intraerythrocytic asexual parasite proteins (PfEMP2 or HRP II).

PMID- 12067341
TI  - CpeR is an activator required for expression of the phycoerythrin operon (cpeBA)
      in the cyanobacterium Fremyella diplosiphon and is encoded in the phycoerythrin
      linker-polypeptide operon (cpeCDESTR).
AB  - In the cyanobacteria, phycobilisomes are assembled from (alphabeta)(6) hexamers
      of the coloured phycobiliproteins, allophycocyanin, phycocyanin and phycoerythrin
      (PE). The precise architecture of the phycobilisome is determined by the various
      colourless linker proteins that bind to the biliprotein hexamers. Genes for beta
      and alpha subunits of PE make up one operon (cpeBA), whereas genes for PE
      associated linker polypeptides are in a second operon. In the chromatically
      adapting cyanobacterium Fremyella diplosiphon green light is required for the
      transcription of both cpeBA and the operon encoding the PE-associated linkers
      (cpeCDE). From the genome of F. diplosiphon we have identified an open reading
      frame, cpeR, which, when expressed from a shuttle plasmid, is capable of
      suppressing various mutations that cause a decrease in PE synthesis. The
      introduction of a shuttle plasmid bearing cpeR+ into wild-type F. diplosiphon
      caused PE expression in red light. Fremyella diplosiphon cpeR-, created by in
      vitro mutagenesis and in vivo homologous recombination, is fully PE and, in this
      strain, cpeCDE is transcribed normally whereas the transcript from cpeBA is
      undetectable. Polymerase chain reaction (PCR) amplification of cDNA showed that
      cpeR is transcribed as part of the cpeCDE operon on an extended transcript. As
      CpeR is an activator required for expression of the cpeBA operon, we propose that
      at the onset of green light the operons cpeCDESTR and cpeBA are expressed in
      series as a genetic cascade.

PMID- 12067342
TI  - Characterization and evidence of mobilization of the LEE pathogenicity island of
      rabbit-specific strains of enteropathogenic Escherichia coli.
AB  - We have characterized the LEE pathogenicity islands (PAIs) of two rabbit-specific
      strains of enteropathogenic E. coli (REPEC), 83/39 (serotype O15:H-) and 84/110-1
      (O103:H2), and have compared them to homologous loci from the human
      enteropathogenic and enterohaemorrhagic E. coli strains, E2348/69 and EDL933, and
      another REPEC strain, RDEC-1. All five PAIs contain a 34 kb core region that is
      highly conserved in gene order and nucleotide sequence. However, the LEE of 83/39
      is significantly larger (59 540 basepairs) than those of the human strains, which
      are less than 44 kb, and has inserted into pheU tRNA. The regions flanking the 34
      kb core of 83/39 contain homologues of two putative virulence determinants,
      efa1/lifA and senA. The LEE of 84/110-1 is approximately 85 kb and is located at
      pheV tRNA. Its core is almost identical to those of 83/39 and RDEC-1, apart from
      a larger espF gene, but its flanking regions contain trcA, a putative virulence
      determinant of EPEC. All three REPEC LEE PAIs contain a gene for an integrase,
      Int-phe. The LEE PAI of 84/110-1 is also flanked by short direct repeats
      (representing the 3'-end of pheV tRNA), suggesting that it may be unstable. To
      investigate this possibility, we constructed a LEE::sacB derivative of 84/110-1
      and showed that the PAI was capable of spontaneous deletion. We also showed that
      Int-phe can mediate site-specific integration of foreign DNA at the pheU tRNA
      locus of E. coli DH1. Together these results indicate possible mechanisms of
      mobilization and integration of the LEE PAI.

PMID- 12067343
TI  - Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron
      acquisition in Candida albicans.
AB  - Efficient iron acquisition is an essential requirement for growth of pathogenic
      organisms in the iron-poor host environment. In Saccharomyces cerevisiae, high
      affinity iron import depends on the multicopper ferroxidase ScFet3. ScFet3
      biogenesis in the trans-Golgi compartment requires a copper-transporting P-type
      ATPase, ScCcc2. Here, we describe the isolation by functional complementation of
      a Ccc2 homologue from the pathogenic yeast Candida albicans. CaCcc2 is
      functionally distinct from a previously described C. albicans copper-transporting
      P-type ATPase, CaCrp1, which appears to be specifically involved in copper
      detoxification. Regulation of CaCCC2 and the phenotype of the homozygous CaCCC2
      deletion indicate that it is required for high-affinity iron import, making it
      the bona fide CCC2 homologue of C. albicans. Remarkably, in a mouse model of
      systemic infection, the Caccc2Delta strain displayed robust proliferation and no
      significant reduction in pathogenicity, suggesting the existence of alternative
      mechanisms of iron uptake from host tissues. We identify haemin and haemoglobin
      as potential iron sources that can be used by C. albicans in a CaCcc2-independent
      manner.

PMID- 12067344
TI  - Specific activation of the Bacillus quorum-sensing systems by isoprenylated
      pheromone variants.
AB  - Natural genetic competence in Bacillus subtilis is controlled by quorum-sensing
      (QS). The ComP- ComA two-component system detects the signalling molecule ComX,
      and this signal is transduced by a conserved phosphotransfer mechanism. ComX is
      synthesized as an inactive precursor and is then cleaved and modified by ComQ
      before export to the extracellular environment. The comQXP' loci of a set of
      natural Bacillus isolates have been sequenced and shown to possess a striking
      polymorphism that determines specific patterns of both activation and inhibition
      of the quorum-sensing response. We have developed a simple purification method
      for the modified peptide signalling pheromones allowing the characterization of
      four distinct ComX molecules representing different pherotypes. Genetic and
      biochemical evidence demonstrate that all the ComX variants are isoprenylated by
      the post-translational modification of a conserved tryptophan residue and that
      the modifications on the ComX peptide backbones vary in mass among the various
      pherotypes. These results give new insights into peptidemediated quorum-sensing
      signalling in Gram-positive bacteria and emphasize the role of isoprenylation in
      bacterial signal transduction.

PMID- 12067345
TI  - Molecular analysis of dimethyl sulphide dehydrogenase from Rhodovulum
      sulfidophilum: its place in the dimethyl sulphoxide reductase family of microbial
      molybdopterin-containing enzymes.
AB  - Dimethyl sulphide dehydrogenase catalyses the oxidation of dimethyl sulphide to
      dimethyl sulphoxide (DMSO) during photoautotrophic growth of Rhodovulum
      sulfidophilum. Dimethyl sulphide dehydrogenase was shown to contain
      bis(molybdopterin guanine dinucleotide)Mo, the form of the pterin molybdenum
      cofactor unique to enzymes of the DMSO reductase family. Sequence analysis of the
      ddh gene cluster showed that the ddhA gene encodes a polypeptide with highest
      sequence similarity to the molybdopterin-containing subunits of selenate
      reductase, ethylbenzene dehydrogenase. These polypeptides form a distinct clade
      within the DMSO reductase family. Further sequence analysis of the ddh gene
      cluster identified three genes, ddhB, ddhD and ddhC. DdhB showed sequence
      homology to NarH, suggesting that it contains multiple iron-sulphur clusters.
      Analysis of the N-terminal signal sequence of DdhA suggests that it is secreted
      via the Tat secretory system in complex with DdhB, whereas DdhC is probably
      secreted via a Sec-dependent mechanism. Analysis of a ddhA mutant showed that
      dimethyl sulphide dehydrogenase was essential for photolithotrophic growth of Rv.
      sulfidophilum on dimethyl sulphide but not for chemo-trophic growth on the same
      substrate. Mutational analysis showed that cytochrome c2 mediated photosynthetic
      electron transfer from dimethyl sulphide dehydrogenase to the photochemical
      reaction centre, although this cytochrome was not essential for
      photoheterotrophic growth of the bacterium.

PMID- 12067346
TI  - Conjugal transfer of the virulence plasmid of Salmonella enterica is regulated by
      the leucine-responsive regulatory protein and DNA adenine methylation.
AB  - Host-encoded functions that regulate the transfer operon (tra) in the virulence
      plasmid of Salmonella enterica (pSLT) were identified with a genetic screen.
      Mutations that decreased tra operon expression mapped in the lrp gene, which
      encodes the leucine-responsive regulatory protein (Lrp). Reduced tra operon
      expression in an Lrp- background is caused by lowered transcription of the traJ
      gene, which encodes a transcriptional activator of the tra operon. Gel
      retardation assays indicated that Lrp binds a DNA region upstream of the traJ
      promoter. Deletion of the Lrp binding site resulted in lowered and Lrp
      independent traJ transcription. Conjugal transfer of pSLT decreased 50-fold in a
      Lrp- background. When a FinO- derivative of pSLT was used, conjugal transfer from
      an Lrp- donor decreased 1000-fold. Mutations that derepressed tra operon
      expression mapped in dam, the gene encoding Dam methyltransferase. Expression of
      the tra operon and conjugal transfer remain repressed in an Lrp- Dam- background.
      These observations support the model that Lrp acts as a conjugation activator by
      promoting traJ transcription, whereas Dam methylation acts as a conjugation
      repressor by activating FinP RNA synthesis. This dual control of conjugal
      transfer may also operate in other F-like plasmids such as F and R100.

PMID- 12067347
TI  - CsrA regulates glycogen biosynthesis by preventing translation of glgC in
      Escherichia coli.
AB  - The carbon storage regulatory system of Escherichia coli controls the expression
      of genes involved in carbohydrate metabolism and cell motility. CsrA binding to
      glgCAP transcripts inhibits glycogen metabolism by promoting glgCAP mRNA decay.
      CsrB RNA functions as an antagonist of CsrA by sequestering this protein and
      preventing its action. In this paper, we elucidate further the mechanism of CsrA
      mediated glgC regulation. Results from gel shift assays demonstrate that several
      molecules of CsrA can bind to each glgC transcript. RNA footprinting studies
      indicate that CsrA binds to the glgCAP leader transcript at two positions. One of
      these sites overlaps the glgC Shine-Dalgarno sequence, whereas the other CsrA
      target is located further upstream in an RNA hairpin. Results from toeprint and
      cell-free translation experiments indicate that bound CsrA prevents ribosome
      binding to the glgC Shine-Dalgarno sequence and that this reduces GlgC synthesis.
      The effect of two deletions in the upstream binding site was examined. Both of
      these deletions reduced, but did not eliminate, CsrA binding in vitro and CsrA
      dependent regulation in vivo. Our findings establish that bound CsrA inhibits
      initiation of glgC translation, thereby reducing glycogen biosynthesis. This
      inhibition of translation probably contributes to destabilization of the glgC
      transcript that was observed previously.

PMID- 12067348
TI  - Genomics of the marA/soxS/rob regulon of Escherichia coli: identification of
      directly activated promoters by application of molecular genetics and informatics
      to microarray data.
AB  - Microarray analyses are providing a plethora of data concerning transcriptional
      responses to specific gene regulators and their inducers but do not distinguish
      between direct and indirect responses. Here, we identify directly activated
      promoters of the overlapping marA, soxS and rob regulon(s) of Escherichia coli by
      applying informatics, genomics and molecular genetics to microarray data obtained
      by others. Those studies found that overexpression of marA, or the treatment of
      cells with salicylate to derepress marA, or treatment with paraquat to induce
      soxS, resulted in elevated transcription of 153 genes. However, only 27 out of
      the promoters showed increased transcription under at least two of the
      aforementioned conditions and eight of those were previously known to be directly
      activated. A computer algorithm was used to identify potential activator binding
      sites located upstream of the remaining 19 promoters of this subset, and
      conventional genetic and biochemical approaches were applied to test whether
      these sites are critical for activation by the homologous MarA, SoxS and Rob
      transcriptional activators. Only seven out of the 19 promoters were found to be
      activated when fused to lacZ and tested as single lysogens. All seven contained
      an essential activator binding site. The remaining promoters were insensitive to
      stimulation by the inducers suggesting that the great majority of elevated
      microarray transcripts either were misidentified or resulted from indirect
      effects requiring sequences outside of the promoter region. We estimate that the
      total number of directly activated promoters in the regulon is less than 40.

PMID- 12067349
TI  - The autoregulatory role of EsaR, a quorum-sensing regulator in Pantoea stewartii
      ssp. stewartii: evidence for a repressor function.
AB  - Capsular polysaccharide synthesis and virulence in the plant pathogenic bacterium
      Pantoea stewartii ssp. stewartii requires the quorum-sensing regulatory proteins,
      EsaR and EsaI, and the diffusible inducer N-(3-oxo-hexanoyl)-L-homoserine
      lactone. Prior mutational studies suggested that EsaR might function as a
      repressor of quorum sensing in the control of capsular polysaccharide synthesis.
      Further, a lux box-like palindromic sequence coinciding with the putative -10
      element of the esaR promoter suggested a possible negative autoregulatory role
      for EsaR. This report presents genetic evidence that EsaR represses the esaR gene
      under inducer-limiting conditions, and that addition of inducer promotes rapid,
      dose-dependent derepression. DNA mobility-shift assays and analyses by surface
      plasmon resonance refractometry show that EsaR binds target DNAs in a ligand-free
      state, and that inducer alters the binding characteristics of EsaR. Physical
      measurements indicate that the EsaR protein binds N-(3-oxo-hexanoyl)-L-homoserine
      lactone, in a 1:1 protein:ligand ratio, and that inducer binding enhances the
      thermal stability of the EsaR protein. These combined genetic and biochemical
      data establish that EsaR regulates its own expression by signal-independent
      repression and signal-dependent derepression. Additionally, we provide evidence
      that EsaR does not govern the expression of the linked esaI gene, thus EsaR has
      no role in controlling coinducer synthesis.

PMID- 12067350
TI  - Structural characterization of lipo-oligosaccharide (LOS) from Yersinia pestis:
      regulation of LOS structure by the PhoPQ system.
AB  - The two-component regulatory system PhoPQ has been shown to regulate the
      expression of virulence factors in a number of bacterial species. For one such
      virulence factor, lipopolysaccharide (LPS), the PhoPQ system has been shown to
      regulate structural modifications in Salmonella enterica var Typhimurium. In
      Yersinia pestis, which expresses lipo-oligosaccharide (LOS), a PhoPQ regulatory
      system has been identified and an isogenic mutant constructed. To investigate
      potential modifications to LOS from Y. pestis, which to date has not been fully
      characterized, purified LOS from wild-type plague and the phoP defective mutant
      were analysed by mass spectrometry. Here we report the structural
      characterization of LOS from Y. pestis and the direct comparison of LOS from a
      phoP mutant. Structural modifications to lipid A, the host signalling portion of
      LOS, were not detected but analysis of the core revealed the expression of two
      distinct molecular species in wild-type LOS, differing in terminal galactose or
      heptose. The phoP mutant was restricted to the expression of a single molecular
      species, containing terminal heptose. The minimum inhibitory concentration of
      cationic antimicrobial peptides for the two strains was determined and compared
      with the wild-type: the phoP mutant was highly sensitive to polymyxin. Thus, LOS
      modification is under the control of the PhoPQ regulatory system and the ability
      to alter LOS structure may be required for survival of Y. pestis within the
      mammalian and/or flea host.

PMID- 12067351
TI  - Identification of XcpP domains that confer functionality and specificity to the
      Pseudomonas aeruginosa type II secretion apparatus.
AB  - Gram-negative bacteria have evolved several types of secretion mechanisms to
      release proteins into the extracellular medium. One such mechanism, the type II
      secretory system, is a widely conserved two-step process. The first step is the
      translocation of signal peptide-bearing exoproteins across the inner membrane.
      The second step, the translocation across the outer membrane, involves the type
      II secretory apparatus or secreton. The secretons are made up of 12-15 proteins
      (Gsp) depending on the organism. Even though the systems are conserved,
      heterologous secretion is mostly species restricted. Moreover, components of the
      secreton are not systematically exchangeable, especially with distantly related
      microorganisms. In closely related species, two components, the GspC and GspD
      (secretin) family members, confer specificity for substrate recognition and/or
      secreton assembly. We used Pseudomonas aeruginosa as a model organism to
      determine which domains of XcpP (GspC member) are involved in specificity. By
      constructing hybrids between XcpP and OutC, the Erwinia chrysanthemi homologue,
      we identified a region of 35 residues that was not exchangeable. We showed that
      this region might influence the stability of the XcpYZ secreton subcomplex.
      Remarkably, XcpP and OutC have domains, coiled-coil and PDZ, respectively, which
      exhibit the same function but that are structurally different. Those two domains
      are exchangeable and we provided evidence that they are involved in the formation
      of homomultimeric complexes of XcpP.

PMID- 12067361
TI  - Efficient embedding technique for preparing small specimens for stereological
      volume estimation: zebrafish larvae.
AB  - Stereological sampling regimes, in particular volume and number estimation, often
      require systematic uniformly random sections throughout a specimen. A method has
      been developed to increase the efficiency of preparing fish larvae for sectioning
      prior to histological or stereological analysis. Embedding a group of larvae in a
      resin block using this technique greatly reduces the quantity of sections
      produced and allows easy assessment of sample groups. Saving time in this way
      therefore makes stereology a more viable research tool.

PMID- 12067362
TI  - Lamellar subcomponents of the cuticular cell membrane complex of mammalian
      keratin fibres show friction and hardness contrast by AFM.
AB  - There is a substantial body of information indicating that 18-methyleicosanoic
      acid (18-MEA) is covalently linked to the outer surface of all mammalian keratin
      fibres and also forms the outer beta-layer of the cuticular cell membrane complex
      (CCMC) which separates the cuticle cells from each other. Low cohesive forces are
      expected between the lipid-containing outer beta-layer and the delta-layer of the
      CCMC, thus providing a weak point for cuticular delamination and presenting a
      fresh layer of 18-MEA to the newly exposed surface. We have used lateral force
      microscopy and force modulation atomic force microscopy (AFM) to examine human
      hair fibres in which the non-covalently linked fatty acids have been removed.
      Examination of the lateral force images of new cuticle surfaces revealed by the
      attrition of overlying cuticle layers showed three separate zones of clearly
      defined frictional contrast. These are thought to correspond with the delta
      layer, the proteinaceous epicuticle and outer beta-layers of the CCMC. The delta
      layer was found to have a thickness of 16 nm (SD = 1 nm, n = 25), comparable to
      the 18.0 nm thickness measured from transverse cross-sections of fibres with
      transmission electron microscopy. Force modulation AFM showed that the outer beta
      layer was softer than the epicuticle and the delta-layer. The frictional contrast
      was removed following treatment with methanolic KOH (0.1 mol dm-3) at 25 degrees
      C for 30 min, suggesting the hydrolysis of the thioester linkage and removal of
      18-MEA from the surface.

PMID- 12067363
TI  - Quantitative phase-amplitude microscopy I: optical microscopy.
AB  - In this paper, the application of a new optical microscopy method (quantitative
      phase-amplitude microscopy) to biological imaging is explored, and the issue of
      resolution and image quality is examined. The paper begins by presenting a
      theoretical analysis of the method using the optical transfer function formalism
      of Streibl (1985). The effect of coherence on the formation of the phase image is
      explored, and it is shown that the resolution of the method is not compromised
      over that of a conventional bright-field image. It is shown that the signal-to
      noise ratio of the phase recovery, however, does depend on the degree of
      coherence in the illumination. Streibl (1985) notes that partially coherent image
      formation is a non-linear process because of the intermingling of amplitude and
      phase information. The work presented here shows that the quantitative phase
      amplitude microscopy method acts to linearize the image formation process, and
      that the phase and amplitude information is properly described using a transfer
      function analysis. The theoretical conclusions are tested experimentally using an
      optical microscope and the theoretical deductions are confirmed. Samples for
      microscopy influence both the phase and amplitude of the light wave and it is
      demonstrated that the new phase recovery method can separate the amplitude and
      phase information, something not possible using traditional phase microscopy. In
      the case of a coherent wave, knowledge of the phase and amplitude constitutes
      complete information that can be used to emulate other forms of microscopy. This
      capacity is demonstrated by recovering the phase of a sample and using the data
      to emulate a differential interference contrast image.

PMID- 12067364
TI  - Quantitative phase-amplitude microscopy II: differential interference contrast
      imaging for biological TEM.
AB  - Although phase contrast microscopy is widespread in optical microscopy, it has
      not been as widely adopted in transmission electron microscopy (TEM), which has
      therefore to a large extent relied on staining techniques to yield sufficient
      contrast. Those methods of phase contrast that are used in biological electron
      microscopy have been limited by factors such as the need for small phase shifts
      in very thin samples, the requirement for difficult experimental conditions, or
      the use of complex data analysis methods. We here demonstrate a simple method for
      quantitative TEM phase microscopy that is suitable for large phase shifts and
      requires only two images. We present a TEM phase image of unstained Radula sp.
      (liverwort spore). We show how the image may be transformed into the differential
      interference contrast image format familiar from optical microscopy. The phase
      images contain features not visible with the other imaging modalities. The
      resulting technique should permit phase contrast TEM to be performed almost as
      readily as phase contrast optical microscopy.

PMID- 12067365
TI  - Multi-field 3D scanning light microscopy of early embryogenesis.
AB  - A computer-controlled microscopy system was devised to allow the observation of
      avian embryo development over an extended time period. Parallel experiments, as
      well as extended specimen volumes, can be recorded at cellular resolution using a
      three-dimensional scanning procedure. The resulting large set of data is
      processed automatically into registered, focal- and positional-drift corrected
      mosaic images, assembled as montages of adjacent microscopic fields. The
      configuration of the incubator and a sterile embryo chamber prevents condensation
      of the humidified culturing atmosphere in the optical path and is compatible with
      both differential interference contrast and epifluorescence optics. As a
      demonstration, recordings are presented showing the large-scale remodelling of
      the embryonic primordial vascular structure.

PMID- 12067366
TI  - Fluorescence lifetime imaging in scanning microscopes: acquisition speed, photon
      economy and lifetime resolution.
AB  - In this paper a detailed discussion is presented of the factors that affect the
      fluorescence lifetime imaging performance of a scanning microscope equipped with
      a single photon counting based, two- to eight-channel, time-gated detection
      system. In particular we discuss the sensitivity, lifetime resolution,
      acquisition speed, and the shortest lifetimes that can be measured. Detection
      systems equipped with four to eight time-gates are significantly more sensitive
      than the two time-gate system. Only minor sensitivity differences were found
      between systems with four or more time-gates. Experiments confirm that the
      lifetime resolution is dominated by photon statistics. The time response of the
      detector determines the shortest lifetimes that can be resolved; about 25 ps for
      fast MCP-PMTs and 300-400 ps for other detectors. The maximum count rate of fast
      MCP-PMTs, however, is 10-100 times lower than that of fast PMTs. Therefore, the
      acquisition speed with MCP-PMT based systems is limited. With a fast PMT operated
      close to its maximum count rate we were able to record a fluorescence lifetime
      image of a beating myocyte in less than one second.

PMID- 12067367
TI  - Direct modulation of the effective sensitivity of a CCD detector: a new approach
      to time-resolved fluorescence imaging.
AB  - In this paper a novel approach to frequency-domain fluorescence lifetime imaging
      (FLIM) is described. In a CCD camera a single pixel is defined by a charge
      pattern on a group of electrodes. By modulation of the pattern of voltages
      defining the pixel structure it is possible to modulate the sensitivity of the
      CCD at radio frequency. The modulation enhances the noise performance of the CCD,
      in contrast to the deterioration in performance seen when an intensifier stage is
      similarly modulated. The new technology has potential applications to a wide
      range of assays as well as in conventional FLIM applications. Unlike intensifier
      based systems, the directly modulated CCD is physically small, inexpensive,
      robust and offers superior resolution and noise performance.

PMID- 12067368
TI  - Measurement of nanosecond time-resolved fluorescence with a directly gated
      interline CCD camera.
AB  - CCD cameras coupled optically to gated image intensifiers have been used for fast
      time-resolved measurements for some years. Image intensifiers have disadvantages,
      however, and for some applications it would be better if the image sensor could
      be gated directly at high speed. Control of the 'charge drain' function on an
      interline-transfer CCD allows the sensor to be switched rapidly from an
      insensitive state. The temporal and spatial properties of the charge drain are
      explored in the present paper and it is shown that nanosecond time resolution
      with acceptable spatial uniformity can be achieved for a small commercial sensor.
      A fluorescence lifetime imaging system is demonstrated, based on a repetitively
      pulsed laser excitation source synchronized to the CCD control circuitry via a
      programmable delay unit.

PMID- 12067369
TI  - Prevalence of verotoxin-producing Escherichia coli (VTEC) and E. coli O157:H7 in
      French pork.
AB  - AIMS: To determination the prevalence of VTEC in pork products and the
      surrounding environment of the pork plant (slaughterhouse and cutting plant), and
      characterization of the VTEC strains isolated (virulence genes and serotype).
      METHODS AND RESULTS: Among the 2146 carcass and pork samples and 876
      environmental samples (swabs of surfaces or materials), 328 (15%) and 170 (19%)
      were PCR-positive for stx genes respectively. VTEC strains were recovered from
      positive samples by colony hybridization or immunoconcentration, serotyped and
      genetically characterized. Strains of E. coli O157:H7 were not isolated from 3
      uidA-positive samples detected by PCR. The VTEC isolates did not harbour eae, ehx
      and uidA genes. CONCLUSIONS: Pigs and pork meat may contain VTEC strains but
      characterization of the strains based on virulence factors showed that the
      potential danger of pork meat appears to be low since although all strains
      harboured a stx gene, they did not have other virulence genes. SIGNIFICANCE OF
      THE STUDY: General hygiene measures appear to be sufficient and specific hygiene
      measures for VTEC are not necessary at this time. The porcine VTEC strains
      isolated in our study probably do not present a hazard.

PMID- 12067370
TI  - Salt stress induces programmed cell death in prokaryotic organism Anabaena.
AB  - AIMS: Our main interest is to check if programmed cell death (PCD) can occur in
      prokaryotic algae and if the morphological and biochemical features of PCD are
      conserved. METHODS AND RESULTS: Using TUNEL labelling, fluorescence and light
      microscopy and DNA gel electrophoresis, we found that cell death with features
      similar to those in metazoan PCD could be induced in different Anabaena strains
      after exposure to univalent-cation salts at moderate concentration. These
      features included specific DNA fragmentation, cytoplasmic vacuolation, and the
      progressive disorganization, fragmentation and subsequent autolysis of the cell
      corpse. Further analyses of cell viability and proteinase activity revealed that
      increased protease activities, decreased DNA content, and loss of plasmalemma
      integrity were related to the PCD process. CONCLUSIONS: The results showed that
      like PCD in eukaryotes, PCD in Anabaena is an active process, and is an
      adaptation to adverse environments. The features of PCD shared between eukaryotes
      and Anabaena suggest that PCD mechanisms are conserved during evolution.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results will contribute greatly to our
      understanding of PCD origin and evolution, and are potentially useful in
      controlling the deluge of algae in some lakes.

PMID- 12067371
TI  - Verotoxin-producing Escherichia coli (VTEC), enteropathogenic E. coli (EPEC) and
      necrotoxigenic E. coli (NTEC) isolated from healthy cattle in Spain.
AB  - AIMS: To determine the prevalence and characteristics of verotoxigenic
      Escherichia coli (VTEC), enteropathogenic E. coli (EPEC) and necrotoxigenic E.
      coli (NTEC) in healthy cattle. METHODS AND RESULTS: Faecal samples from 412
      healthy cattle were screened for the presence of VTEC, EPEC and NTEC. Four
      isolates from each sample were studied. VTEC, EPEC and NTEC were isolated in
      8.7%, 8.2% and 9.9% of the animals, respectively. VTEC and NTEC were isolated
      more frequently from calves and heifers than from adults. Seventy (4.2%), 69
      (4.2%) and 74 (4.5%) of the 1648 E. coli isolates were VTEC, EPEC and NTEC,
      respectively. Seventeen (24.3%) of the VTEC strains were eae-positive. Thirty-six
      (51.4%) of VTEC strains belonged to E. coli serogroups associated with
      haemorrhagic colitis and haemolytic uraemic syndrome in humans. The serogroups
      most prevalent among the EPEC strains were O10, O26, O71, O145 and O156.
      CONCLUSIONS: Healthy cattle are a reservoir of VTEC, EPEC and NTEC. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Although most of the VTEC strains were eae-negative, a
      high percentage of VTEC strains belonged to serogroups associated with severe
      disease in humans.

PMID- 12067372
TI  - Comparison of genotypic and phenotypic techniques for assessing the variability
      of the fungus Epicoccum nigrum.
AB  - AIMS: The diversity within a collection of worldwide isolates of Epicoccum nigrum
      has been studied using several phenotypic approaches. In addition, the abilities
      of phenotypic and genotypic techniques for the differentiation of a set of
      isolates are compared. METHODS AND RESULTS: The methodology used include the
      study of isozymes (acetyl esterase and alkaline phosphatase), HPLC profile of
      metabolites and antibiotic activities against a panel of bacteria, yeasts and
      filamentous fungi, and cytotoxicity against three mammalian cell lines. Two
      procedures for assessing the relationships within a collection of isolates, using
      a combination of the techniques, were evaluated, comparing the advantages and
      disadvantages of each method. CONCLUSIONS: The results showed that each
      individual technique allows differentiation of the isolates studied to some
      degree and that the information provided by each technique could be considered as
      complementary. Genotypic techniques were more powerful than the phenotypic ones
      to discriminate among the strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      work evaluates the predictive value of several phenotypic techniques on a
      collection of fungal isolates, and compares the results obtained with genotypic
      techniques performed on the same strains.

PMID- 12067373
TI  - Immunoassays to detect the serum antibody response of cattle to infection with
      Salmonella Typhimurium definitive type 104 and following vaccination with Bovivac
      S.
AB  - AIMS: To use ELISA and immunoblotting assays to examine the serum antibody
      response of cattle infected with Salmonella Typhimurium DT104 and following
      vaccination with Bovivac S. METHODS AND RESULTS: Three hundred and twenty-nine
      cattle, including 16 shedding multiresistant Salmonella Typhimurium DT104, were
      screened for serum antibodies binding to O=1, 4, 5, 12 lipopolysaccharide (LPS)
      antigens before and after vaccination with Bovivac S. Sera with an ELISA reading
      of 0.9A405 or above were shown to contain antibodies, of the IgG-class only, to
      the LPS of Salmonella Typhimurium using immunoblotting. Prior to vaccination,
      only 11 cattle had serum IgG-class antibodies to the O=4, 5 LPS antigens, and of
      these one also had antibodies to outer membrane proteins and H=i flagellar
      antigens. Following vaccination, 87 out of 315 cattle developed serum antibodies
      to the LPS of Salmonella Typhimurium. CONCLUSIONS: Evidence of infection of
      cattle with Salmonella Typhimurium was readily obtained with an LPS-based ELISA
      in association with an immunoblotting procedure, supplementing existing
      bacteriological procedures. This enabled the detection of an increase in the
      number of cattle with serum antibodies to Salmonella Typhimurium LPS following
      vaccination with Bovivac S. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      immunoassays described provided evidence of infection with Salmonella Typhimurium
      and served as a valuable adjunct to established bacteriology.

PMID- 12067374
TI  - Cloning and sequencing of the gene encoding X-prolyl-dipeptidyl aminopeptidase
      (PepX) from Streptococcus thermophilus strain ACA-DC 4.
AB  - AIMS: To clone and sequence the pepX gene from Streptococcus thermophilus.
      METHODS AND RESULTS: Three pairs of primers were used in polymerase chain
      reactions using as template the total DNA from Strep. thermophilus ACA-DC 4 in
      order to amplify, clone and sequence the pepX gene. Sequence analysis revealed an
      open reading frame of 2268 nucleotides encoding a protein of 755 amino acids. The
      calculated molecular mass of 85 632 Da agreed well with the apparent molecular
      mass of 80 000 Da previously determined by sodium dodecyl sulphate-polyacrylamide
      gel electrophoresis and gel filtration for the monomeric form of the purified
      enzyme. CONCLUSIONS: The pepX gene from Strep. thermophilus ACA-DC 4 was cloned
      and sequenced. The PepX protein showed significant sequence similarity with PepX
      enzymes from other lactic acid bacteria and contained a motif which was almost
      identical with the active site motif of the serine-dependent PepX family.
      SIGNIFICANCE AND IMPACT OF THE STUDY: There are economic and technological
      incentives for accelerating and controlling the process of cheese ripening. To
      achieve this, starters may be modified by introducing appropriate genes from
      other food-grade bacteria. New or additional peptidase activities may alter or
      improve the proteolytic properties of lactic acid bacteria.

PMID- 12067375
TI  - Oligonucleotide probe for detecting Enterobacteriaceae by in situ hybridization.
AB  - AIMS: To develop oligonucleotide probes for visualizing bacteria belonging to
      Enterobacteriaceae. METHODS AND RESULTS: 24-mer oligonucleotide probe (probe D)
      was designed by comparison of 16S rDNA sequences of 35 species of
      Enterobacteriaceae, eight species of Vibrionaceae and six species of
      Pasteurellaceae. The sequence of the probe corresponding to the complementary
      sequence of a position 1251-1274 of Escherichia coli 16S rRNA was found to be a
      highly conserved region of 16S rDNA sequence in Enterobacteriaceae different from
      that of Vibrionaceae and Pasteurellaceae. The fluorescent dye-labelled probe was
      tested for the specificity by in situ hybridization and epifluorescence
      microscopy. Seventy-six out of 78 strains belonging to Enterobacteriaceae were
      visualized in an optimal hybridization condition. No bacterial strains belonging
      to Vibrionaceae (31 strains) and Gram-positive bacteria (three strains) were
      visualized. CONCLUSIONS: In situ hybridization using probe D allows the detection
      of bacterial cells belonging to Enterobacteriaceae without false positive
      reaction. SIGNIFICANCE AND IMPACT OF THE STUDY: In situ hybridization techniques
      using the probe D are potential tools for detecting Enterobacteriaceae in food
      and water samples.

PMID- 12067376
TI  - Escherichia coli survival in groundwater and effluent measured using a
      combination of propidium iodide and the green fluorescent protein.
AB  - AIMS: The aim of this study was to deterimine the survival of an enteric
      bacterium in anaerobic groundwater and effluent microcosms using the green
      fluorescent protein (GFP) marker gene in combination with the viability indicator
      propidium iodide (PI). METHODS AND RESULTS: The pEGFP vector (Clontech) was
      transformed into Escherichia coli DH5alpha and was stable for at least 100
      generations of growth in nonselective medium at 28 degrees C and 37 degrees C.
      Using an epifluorescent microscope, GFP cells could be detected under blue light
      (450-490 nm) and the numbers of PI-positive GFPs could be detected under green
      light (530-560 nm). GFP-tagged E. coli could be detected for at least 132 d in
      sterilized water microcosms. GFP fluorescence was not lost from the culturable
      cell population for the duration of the experiment. However, a slow decline in
      the number of GFP-fluorescent cells in sterilized groundwater was observed.
      Escherichia coli die-off and loss of green fluorescence was more rapid in
      nonsterilized waters than in sterilized. Viable numbers of the GFP-tagged E. coli
      determined by PI counterstaining were compatible with numbers of colony-forming
      units. CONCLUSIONS: The long-term survival of E. coli and maintainance of GFP
      conferred fluorescence in these cells was demonstrated in both groundwater and
      effluent, under sterilized conditions. However, severe starvation and/or the
      presence of indigenous microorganisms were found to be factors affecting the
      maintenance of fluorescence in dead or dying cells. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This study demonstrates the successful application of PI with GFP
      tagging to monitor long-term bacterial survival in nutrient-limited conditions
      and mixed microbial populations.

PMID- 12067377
TI  - Phenotypic study by numerical taxonomy of strains belonging to the genus
      Aeromonas.
AB  - AIMS: This study was undertaken to cluster and identify a large collection of
      Aeromonas strains. METHODS AND RESULTS: Numerical taxonomy was used to analyse
      phenotypic data obtained on 54 new isolates taken from water, fish, snails,
      sputum and 99 type and reference strains. Each strain was tested for 121
      characters but only the data for 71 were analysed using the 'SSM' and 'SJ'
      coefficients, and the UPGMA clustering algorithm. At SJ values of > or = 81.6%
      the strains clustered into 22 phenons which were identified as Aer. jandaei, Aer.
      hydrophila, Aer. encheleia, Aer. veronii biogroup veronii, Aer. trota, Aer.
      caviae, Aer. eucrenophila, Aer. ichthiosmia, Aer. sobria, Aer. allosaccharophila,
      Aer. media, Aer. schubertii and Aer. salmonicida. The species Aer. veronii
      biogroup sobria was represented by several clusters which formed two phenotypic
      cores, the first related to reference strain CECT 4246 and the second related to
      CECT 4835. A good correlation was generally observed among this phenotypic
      clustering and previous genomic and phylogenetic data. In addition, three new
      phenotypic groups were found, which may represent new Aeromonas species.
      CONCLUSIONS: The phenetic approach was found to be a necessary tool to delimitate
      and identify the Aeromonas species. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Valuable traits for identifying Aeromonas as well as the possible existence of
      new Aeromonas species or biotypes are indicated.

PMID- 12067378
TI  - Adaptive resistance to benzalkonium chloride, amikacin and tobramycin: the effect
      on susceptibility to other antimicrobials.
AB  - AIMS: To produce strains of antimicrobial-resistant Pseudomonas aeruginosa via
      adaptation to benzalkonium chloride, amikacin and tobramycin and to then examine
      the incidence, or otherwise, of cross-resistance between antibiotics and between
      antibiotics and benzalkonium chloride. METHODS AND RESULTS: Adaptation was
      obtained by progressive subculturing in subinhibitory concentrations of the
      antimicrobials. Pseudomonas aeruginosa NCIMB 10421 adapted to grow in high
      concentrations of benzalkonium chloride (BC) had lower MIC to antibiotics than
      the wild type, whereas Ps. aeruginosa adapted to grow in antibiotics had greater
      MIC to benzalkonium by a small degree. CONCLUSIONS: Adaptive resistance to BC of
      Ps. aeruginosa generally produced cultures with a decrease in resistance to
      several antibiotics. Adaptive resistance to the aminoglycosides Ak and Tm
      produced a low-level increase in tolerance to BC. The adaptive mechanisms of
      resistance appear to be different for the different types of antimicrobials used.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The relationships between biocide and
      antibiotic resistance are complex. It appears, from this study, that an organism
      resistant to a common biocide can become sensitive to antibiotics, but the
      converse was not true. Could this observation be used in a strategy to alleviate
      antibiotic resistance?

PMID- 12067379
TI  - Entry of Vibrio harveyi and Vibrio fischeri into the viable but nonculturable
      state.
AB  - AIMS: Physiological responses of marine luminous bacteria, Vibrio harveyi (ATCC
      14216) and V. fischeri (UM1373) to nutrient-limited normal strength (35 ppt iso
      osmolarity) and low (10 ppt hypo-osmolarity) salinity conditions were determined.
      METHODS AND RESULTS: Plate counts, direct viable counts, actively respiring cell
      counts, nucleoid-containing cell counts, and total counts were determined. Vibrio
      harveyi incubated at 22 degrees C in nutrient-limited artificial seawater (ASW)
      became nonculturable after approximately 62 and 45 d in microcosms of 35 ppt and
      10 ppt ASW, respectively. In contrast, V. fischeri became nonculturable at
      approximately 55 and 31 d in similar microcosms. Recovery of both culturability
      and luminescence of cells in the viable but nonculturable state was achieved by
      addition of nutrient broth or nutrient broth supplemented with a carbon source,
      including luminescence-stimulating compounds. Temperature upshift from 22 degrees
      C to 30 degrees C or 37 degrees C did not result in recovery from
      nonculturability. CONCLUSIONS: The study confirms entry of V. harveyi and V.
      fischeri into the viable but nonculturable state under low-nutrient conditions
      and demonstrates nutrient-dependent resuscitation from this state. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study confirms loss of luminescence of V. harveyi
      and V. fischeri on entry into the viable but nonculturable state and suggests
      that enumeration of luminescent cells in water samples may be a rapid method to
      deduce the nutrient status of a water sample.

PMID- 12067380
TI  - Sequence analysis of the genes encoding for the major virulence factors of
      Bacillus anthracis vaccine strain 'Carbosap'.
AB  - AIMS: This study was performed to analyse the molecular characteristics of genes
      encoding for the major virulence factors in Bacillus anthracis vaccine strain
      'Carbosap' compared with the wild B. anthracis strain, to evaluate the basis of
      attenuation. METHODS AND RESULTS: The molecular characteristics of the B.
      anthracis 'Carbosap' vaccine strain, used as vaccine in Italy, were analysed in
      comparison with a B. anthracis virulent strain. Despite the presence of the two
      virulence plasmids pXO1 and pXO2, the 'Carbosap' strain proved to be protective
      for cattle. The presence of the regulatory genes atxA and pagR and the gerX
      operon, known to be involved in the virulence, was verified. In addition, all
      genes were sequenced. The results showed that no molecular differences between
      'Carbosap' and the virulent strain were evident. CONCLUSIONS: The results of this
      study indicate that the attenuation of the 'Carbosap' vaccine strain is not due
      to the lack of virulence genes or to modifications occurring on the sequence of
      these genes. Therefore, other virulence factors, still unknown, could be involved
      in the pathogenic mechanisms. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper
      adds new information regarding the molecular characteristics of the vaccine
      strain 'Carbosap' and highlights the need to better understand the virulence
      factors involved in the pathogenicity of B. anthracis strains.

PMID- 12067381
TI  - Transformation and expression of an anaerobic fungal xylanase in several strains
      of the rumen bacterium Butyrivibrio fibrisolvens.
AB  - AIMS: To obtain reliable transformation of a range of Butyrivibrio fibrisolvens
      strains and to express a Neocallimastix patriciarum xylanase gene in the
      recipients. METHODS AND RESULTS: Eight strains (H17c, E14, LP1309, LP1028, AR11a,
      OB156, LP210B and LP461A) of Bu. fibrisolvens were transformed by the Gram
      positive vector pUB110. A xylanase expression/secretion cassette containing Bu.
      fibrisolvens promoter and signal peptide elements fused to catalytic domain II of
      the N. patriciarum xylanase A cDNA (xynANp) was inserted into pUB110 to create
      the plasmid pUBxynA. pUBxynA was used to transform seven of the Bu. fibrisolvens
      strains transformed by pUB110. In strain H17c pUBxynA, which produced native
      xylanase, 2.46 U mg-1 total xylanase activity was produced with 45% extracellular
      xylanase. In strain H17c pUMSX, 0.74 U mg-1 total xylanase activity was produced
      with 98% extracellular xylanase. H17c pUBxynA exhibited increased (28.7%)
      degradation of neutral detergent fibre compared with unmodified H17c; however,
      progressive loss of pUBxynA was observed in long-term cultivation. CONCLUSIONS: A
      stable transformation system was developed that was applicable for a range of Bu.
      fibrisolvens strains and high levels of expression of a recombinant xylanase were
      obtained in H17c which lead to increased fibre digestion. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This stable transformation system with the accompanying recombinant
      plasmids will be a useful tool for further investigation aimed at improving
      ruminal fibre digestion.

PMID- 12067382
TI  - Lactococcus lactis DPC5598, a plasmid-free derivative of a commercial starter,
      provides a valuable alternative host for culture improvement studies.
AB  - AIMS: To generate a plasmid-free derivative of an extensively used industrial
      starter strain Lactococcus lactis DPC4268, which could be used as a backbone
      strain for starter improvement programmes. METHODS AND RESULTS: DPC4268
      containing four large plasmids was subjected to high temperature plasmid curing
      resulting in derivatives, each with a different plasmid complement of one, two or
      three different plasmids in addition to a plasmid-free derivative. Industrially
      relevant phenotypes were assigned to each plasmid on the basis of detailed
      phenotypic and genetic analyses and these were (a) proteinase activity (Prt, 60
      kb) (b) lactose fermentation (Lac, 55 kb) (c) bacteriophage adsorption inhibition
      (Ads, 44 kb) and (d) type I restriction/modification (R/M, 40 kb). The plasmid
      free variant of DPC4268 was shown to be transformable at frequencies comparable
      to the common laboratory strain L. lactis MG1614. Furthermore its genome was
      demonstrated to be significantly different from the laboratory strains L. lactis
      MG1614 and the recently sequenced L. lactis IL1403 genomes by pulsed-field gel
      electrophoresis. CONCLUSIONS: This study produced an easily transformable plasmid
      free derivative which was genomically different from both MG1614 and IL1403. In
      addition, important plasmid-borne industrial traits, including two phage
      resistance mechanisms, were identified in DPC4268. SIGNIFICANCE AND IMPACT OF THE
      STUDY: L. DPC4268 is a vitally important commercial strain used in the
      manufacture of Cheddar cheese. The generation of a plasmid-free derivative may
      provide an important backbone strain as a basis for future strain improvement
      purposes.

PMID- 12067383
TI  - Interaction of ozone and negative air ions to control micro-organisms.
AB  - AIMS: The aims of this study were to investigate the effect of ozone and/or
      negative air ions (NAI) on the viability of bacteria. METHODS AND RESULTS: Dilute
      cell suspensions of Pseudomonas fluorescens, Erwinia carotovora pv. carotovora
      and Escherichia coli were inoculated onto agar and subsequently exposed to ozone
      and/or NAI. Ozone concentration was maintained at 100 +/- 5 nl l-1 and NAI at 106
      ml-1. When exposed to a combination of ozone and NAI, viability among all three
      bacterial species decreased more rapidly when they were inoculated onto potato
      dextrose agar (PDA) than onto nutrient agar (NA). A subsequent test examined the
      effect of ozone and NAI alone or in combination on the bacteria inoculated onto
      PDA only. Treatment with NAI alone had no killing effect on any of the bacterial
      species. However, a strong interaction between ozone and NAI was observed.
      Pseudomonas fluorescens was most susceptible to the combined treatment. Cell
      viability was reduced to 0.7% after 6 h, while 76% of the cells remained viable
      when exposed to ozone alone. Viability of Erwinia carotovora pv. carotovora was
      reduced to 4% after 6 h in the combined treatment compared with 69% when exposed
      to ozone alone. Escherichia coli was relatively more resistant to the combined
      treatment; viability was reduced to 40% after 11 h compared with 70% in the ozone
      alone treatment. CONCLUSIONS: A strong synergism between ozone and NAI on
      bacterial cell death was found, but the degree of this effect varied depending on
      bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: The synergism of ozone
      with NAI may provide an effective method of reducing food-borne disease and decay
      of fresh produce.

PMID- 12067384
TI  - Usefulness of a TaqMan-based polymerase chain reaction assay for the detection of
      the fish pathogen Flavobacterium psychrophilum.
AB  - AIMS: This study developed a new diagnostic method for the bacterium
      Flavobacterium psychrophilum based on a TaqMan polymerase chain reaction (PCR)
      assay. METHODS AND RESULTS: Based on reported and newly designed PCR probes, a
      rapid procedure, that requires no post-PCR processing, was developed for the
      detection of F. psychrophilum by measuring the fluorescence produced during PCR
      amplification. Primers were designed to amplify a 971-bp fragment of the 16S rRNA
      as the target. When different F. psychrophilum strains and other bacterial
      species, that are taxonomically and ecologically related, were assayed the
      fluorogenic test was 100% specific in identifying all of the F. psychrophilum
      strains. The sensitivity of the assay was found to be 1.1 pg DNA and the assay
      was linear over a range of 0.1 pg-11.2 ng. With pure cultures of F.
      psychrophilum, the assay was linear over the range 0.4-4.7 x 104 cfu and was able
      to detect 4.7 cfu per reaction. The analysis was reproducible using either
      extracted DNA or pure culture. Results using artificially infected fish and
      diseased fry from natural fish farm outbreaks showed that the assay was useful
      for diagnosis. CONCLUSIONS: The data showed that the assay was as specific,
      sensitive, reproducible and rapid but less toxic than the PCR assays described
      and so very useful for the diagnosis of these micro-organisms. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This new approach permits a rapid, easy and safe routine
      laboratory diagnosis of F. psychrophilum.

PMID- 12067385
TI  - Influence of resistant starch on the SCFA production and cell counts of butyrate
      producing Eubacterium spp. in the human intestine.
AB  - AIMS: The genus Eubacterium, which is the second most common genus in the human
      intestine, includes several known butyrate producers. We hypothesized that
      Eubacterium species play a role in the intestinal butyrate production and are
      inducible by resistant starch. METHODS AND RESULTS: In a human pilot study
      species-specific and group-specific 16S rRNA-targeted, Cy3 (indocarbocyanine)
      labelled oligonucleotide probes were used to quantify butyrogenic species of the
      genera Eubacterium, Clostridium and Ruminococcus. Following the intake of RS type
      III a significant increase in faecal butyrate but not in total SCFA was observed.
      However, increase in butyrate was not accompanied by a proliferation in the
      targeted bacteria. CONCLUSIONS: The tested Eubacterium species have the capacity
      to produce butyrate but do not appear to play a major role for butyric acid
      production in the human intestine. SIGNIFICANCE AND IMPACT OF THE STUDY: In view
      of the fact that the bacteria responsible for butyrate production are largely
      unknown, it is still difficult to devise a dietary intervention to stimulate
      butyrogenic bacteria in a targeted way.

PMID- 12067386
TI  - Phenotypic degeneration occurs during sector formation in Metarhizium anisopliae.
AB  - AIMS: The formation of sectors was observed during subculturing of an isolate of
      the entomopathogenic fungus Metarhizium anisopliae, a fungus used for biological
      control of insect pests. The aim of the investigation was to establish whether
      sector formation was accompanied by changes in physiological characters. METHODS
      AND RESULTS: Four degenerative morphological states, with reduced sporulation
      capacity, were characterized. Subcultures were taken from each sector and four
      new culture lines established. The new lines were further subcultured every 21 d.
      A physiological assessment of each line was undertaken after 42 d using TLC of
      secondary metabolites and fluorogenic enzyme tests. Full sporulation capacity was
      not regained on subculture, although some cultures recovered partially. Changes
      in secondary metabolite profiles and the loss in detection of activity of
      specific enzymes were observed. CONCLUSIONS: Sector formation was frequently
      accompanied by changes in the ability to produce secondary metabolites and
      enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: The results illustrate the
      importance of maintaining the stability of important cultures during routine
      subculture. The consequences could have significant implications if degenerate
      cultures are used as inocula for liquid fermentation cultures or industrial scale
      production.

PMID- 12067387
TI  - Cross-contamination of carcasses and equipment during pork processing.
AB  - AIMS: The cross-contamination events within a commercial pork processing line
      were examined by a combination of ERIC-PCR DNA fingerprinting of Escherichia coli
      and plate counts. METHODS AND RESULTS: Sponge sampling of environmental surfaces
      and carcasses was performed over an 8-h processing period. Prior to the start of
      processing the scraper and dry polisher blades were found to harbour substantial
      Enterobacteriaceae and Escherichia coli populations. From plate count data the
      key cross-contamination site for the transfer of bacteria between carcasses
      occurred during evisceration. However, DNA fingerprints of representative E. coli
      isolates identified that genotypes initially present on the scraper/dry polisher
      became distributed on wet polisher blades, band-saw and butcher's hands despite a
      singeing step being performed post dry polishing. A high proportion of E. coli on
      post-eviscerated carcasses could be traced to down-stream (pre-singe)
      environmental contact surfaces. CONCLUSIONS: DNA fingerprinting has demonstrated
      that E. coli and potential enteric pathogens can be transferred between pork
      carcasses throughout the processing line. In this respect scalding and singeing
      cannot be relied upon to control cross-contamination of enteric bacteria between
      carcasses. SIGNIFICANCE AND IMPACT OF THE STUDY: Sole reliance on indicator
      organism counts to identify cross-contamination events as currently advocated is
      limited.

PMID- 12067388
TI  - Calorimetric determination of inactivation parameters of micro-organisms.
AB  - AIMS: This study aimed to apply differential scanning calorimetry (DSC) to
      evaluate the thermal inactivation kinetics of bacteria. METHODS AND RESULTS: The
      apparent enthalpy (DeltaH) of Escherichia coli cells was evaluated by a
      temperature scan in a DSC after thermal pretreatment in the calorimeter to
      various temperatures between 56 and 80 degrees C. Conventional semilogarithmic
      survival curve analysis was combined with a linearly increasing temperature
      protocol. Calorimetrically determined D and z values were compared to those
      obtained from plate count data collected under isothermal conditions to validate
      the new approach. CONCLUSIONS: The calculated D values using both apparent
      enthalpy and viability data for cells heat treated in the DSC were similar to the
      D values obtained from isothermal treatment. Temperatures for 1 through 10-log
      microbial population reductions, calculated from plate count and enthalpy data,
      were in agreement within 0.5-2.4 degrees C at a 4 degrees C min-1 heating rate.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This novel calorimetric method provides an
      approach to obtain accurate and reproducible kinetic parameters for inactivation.
      The calorimetric method here described is time efficient and is conducted under
      conditions similar to food processing conditions.

PMID- 12067390
TI  - The management of persistent pain in older persons.

PMID- 12067391
TI  - Elder abuse, neglect and restraint--research before review.

PMID- 12067393
TI  - Two theories/a sharper lens: the staff nurse voice in the workplace.
AB  - AIM OF THE PAPER: This paper (1) introduces the two theoretical frameworks,
      Silencing the Self and the Framework of Systemic Organization (2) describes the
      design and findings briefly of a study exploring spillover in nurses utilizing
      the frameworks, and (3) discusses the process and value of theory triangulation
      when conducting research in the context of complex nursing systems phenomena
      where gender, professional work, and gender identity merge. BACKGROUND/RATIONALE:
      A research study was designed to analyse the actual workplace behaviours of
      nurses in the context of their lives at work and outside work. An exploration of
      theoretical frameworks that could direct the measurement of the phenomena in
      question led to the use of two frameworks, the Framework of Systemic Organization
      (Friedemann 1995) and the Silencing the Self Theory (Jack 1991), and the creation
      of a valid and reliable summative rating instrument (the Staff Nurse Workplace
      Behaviours Scale, SNWBS). DESIGN/METHODS: A descriptive correlational design was
      used to measure behaviours between work and home. RESULTS/FINDINGS: There were
      statistically significant relationships found between workplace behaviours,
      family behaviours, and silencing behaviours as measured by the two separate
      scales measuring framework concepts. CONCLUSIONS: Although both theories had
      different origins and philosophical tenets, the findings of a research study
      created an opportunity to integrate the concepts of each and unexpectedly
      increase and broaden the understanding of spillover for women who are often
      nurses.

PMID- 12067394
TI  - Nursing as means of governmentality.
AB  - BACKGROUND: This paper conceptualizes nursing as a health profession in
      transformation at the beginning of the 21st century. We frame our analysis using
      Michel Foucault's concept of governmentality. While extensively quoted and used
      in other disciplines, the work of the late French philosopher has been cited
      infrequently in the nursing literature. Yet a closer look at his work reveals how
      Foucault offers a relevant entry point for revisiting nursing theory and nursing
      practice. AIM OF THE PAPER: aim of this paper is to reflect on nursing practice
      as it is inscribed within the state's modus operandi. We discuss the prevalent
      notion that nurses are powerless and suggest they do exercise power in many ways
      and that they are a powerful group. RESULTS: In this paper we show how nursing is
      a means of governmentality of individuals and of the population because its
      practices contribute to the management of society through a vast range of power
      techniques. These techniques range from disciplining individuals to promoting
      discourses that construct desirable subjectivities. Within this perspective, the
      emergence of political aspects of nursing theory and nursing practice are made
      explicit. CONCLUSION: We explore the limits and potentials of the concept of
      governmentality to the understanding of nursing as a health profession. This
      concept can generate a form of critical immobilism, but also promotes a more
      politically complex understanding of nursing practice.

PMID- 12067395
TI  - Benner's remnants: culture, tradition and everyday understanding.
AB  - BACKGROUND: Benner's account of meaning and embodiment in nursing depends on a
      theory which she has never fully articulated, although she makes numerous
      allusions to it. Behind the background of shared meanings hovers something called
      'culture', which provides each individual with meaning, determines what counts as
      real for her, and actively hands down interpretation-laden practices. This view
      is based, Benner claims, on the Heideggerian assumption that the meaning and
      organization of a culture precedes individual meaning-giving activity. AIM: I
      explore Benner's implicit view of culture, drawing on her published work over 15
      years, and offer an appraisal of it. In doing so, I attempt to make sense of some
      rather strange remarks Benner has recently made about 'remnants' of Cartesian and
      Kantian thinking being found in the everyday understandings of people with
      asthma. METHODS: The concept of culture is developed with reference to both
      Benner's own work and that of the anthropologist, Clifford Geertz, whose work she
      frequently cites. Having identified the principal tenets of what we might
      conveniently call the Benner-Geertz theory, I proceed to interrogate the theory,
      using the recent anthropological literature -- and, in particular, materialist
      attacks on the idea of culture as a system of meanings -- in order to cast doubt
      on it. I also review, very briefly, an alternative way of understanding
      'culture', which is not vulnerable to the same criticisms. CONCLUSIONS: Benner's
      implicit theory of culture is revealed, somewhat ironically, as an inverted form
      of Cartesian dualism. Its intellectual provenance is not Heidegger, who appears
      to reject it, but the sort of American sociology associated with Talcott Parsons.
      As a corollary, it is suggested that Benner's 'remnants' analogy cannot be
      justified, and that the idea of Cartesian and Kantian concepts permeating Western
      culture, infecting both the providers and receivers of health care, is a myth.

PMID- 12067396
TI  - Storytelling and the interpretation of meaning in qualitative research.
AB  - AIM: This paper reviews literature on narrative analysis and illustrates the
      meaning-making function of stories of chronic illness through analysis and
      discussion of two case studies from a study of acute episodes of chronic
      obstructive pulmonary disease (COPD). BACKGROUND: Individuals living with COPD
      experience acute exacerbations characterized by extreme dyspnea, but there has
      been little research to provide understanding of these events from the
      perspectives of individuals with COPD, family caregivers, and nurses. Narrative
      analysis -- considered in the context of the aims of qualitative research --
      illuminates how these people make sense of acute exacerbation events by telling
      stories. DESIGN AND METHODS: In an ethnographic study, 10 patient-family nurse
      units in two Canadian general hospitals participated in interviews concerning
      acute episodes of COPD. Narrative analysis enabled identification of several
      story forms and their functions. RESULTS: Examples were found of a story told
      twice with different meanings, and of a patient's 'death story' used to
      communicate distrust of the nurse's ability to recognize the seriousness of
      distress and implications for its potential course. These examples are presented,
      and interpreted with respect to issues of meaning. CONCLUSIONS: The analysis
      indicates that stories told by patients in the context of nurse-client
      interactions inform understanding of the individual's acute exacerbation events
      beyond the biophysical.

PMID- 12067397
TI  - Hardiness, work support and psychological distress among nursing assistants and
      registered nurses in Quebec.
AB  - BACKGROUND: Although nursing assistants (NAs) represent a large segment of
      Canadian health care providers, little is known about psychosocial factors
      related to their physical and psychological well-being and how these compare with
      their registered nurse (RN) counterparts. AIM: Guided by Maddi and Kobasa's
      theoretical framework of Factors Affecting Health-Illness Status, the purpose of
      the present study was to examine relationships among hardiness, psychological
      distress and work support in NAs, and to compare results with those from a sample
      of RNs. METHOD: A random sample of 171 NAs in Quebec completed self-report
      questionnaires. The study instruments included validated French-Canadian versions
      of Kobasa's Hardiness Scale, Ilfeld's Psychiatric Symptom Index, and Moos' Work
      Relationship Index. RESULTS: As theoretically predicted, statistically
      significant correlations were found between hardiness and psychological distress
      (r = -0.42; P < 0.001), hardiness and work support (r = 0.27; P < 0.001), and
      between work support and psychological distress (r = -0.21; P < 0.001). Using a
      mediational model and multiple regression analyses, hardiness among NAs was found
      to be a significant mediator between work support and psychological distress.
      Comparative analyses revealed that whereas NAs and RNs reported similar levels of
      psychological distress (P = 0.25) and work support (P = 0.13), NAs reported
      significantly less hardiness (t = -5.58; P < 0.01). In addition, NAs and RNs
      reported significantly more psychological distress than the general population of
      Quebec, Canada (t = 9.07 and 22.84, P < 0.01, respectively). CONCLUSION: Results
      add support to Maddi and Kobasa's theoretical propositions linking personal and
      contextual resources to health-related outcomes and offer insights into specific
      factors that may affect the health and well-being of both NAs and RNs as well as
      their work climate.

PMID- 12067398
TI  - Ethnicity in pressure ulcer risk assessment, with specific relation to the
      Pakistani ethnic minority in Burton, England.
AB  - BACKGROUND: There has been little work on ethnicity related to pressure ulcers in
      general and little or nothing specific to South Asians, and the Pakistani ethnic
      group in particular. AIM: To explore the relevance of ethnicity in pressure
      ulcers. METHODS: All admissions over a 5-year period to a District General
      Hospital in Burton, United Kingdom (UK) were considered where data were present
      on Waterlow Score, ethnicity and pressure sore status. Logistic regression
      analysis was conducted using ethnicity and other variables to predict ulcer
      formation. RESULTS; Age is predictive, but ethnicity was not found to be a
      significant predictor. CONCLUSION: There is no evidence that members of the
      Pakistani ethnic minority are at higher risk than the majority White population
      in Burton, with respect to pressure ulcers.

PMID- 12067399
TI  - Gender differences of parental distress in children with cancer.
AB  - BACKGROUND: Reports published over the last few decades present contradictory
      findings about the psychological distress and coping patterns of parents whose
      children have cancer. Although an increasing number of studies have focused on
      psychological distress and the adjustment process that parents experience when
      their children are diagnosed with cancer, few of these studies have been
      conducted in Taiwan. AIMS: Gender differences of parental distress experienced by
      Taiwanese mothers and fathers (164 couples) whose children were undergoing
      treatment for cancer were investigated. METHODS: Parenting stress, psychological
      distress, somatization, as well as marital satisfaction were compared between
      mothers and fathers whose children had cancer. RESULTS: Mothers averaged
      significantly higher levels than fathers for all forms of distress. Mothers and
      fathers whose children had been diagnosed within the previous 2 months reported
      higher levels of depression, anxiety, and global stress than those in the other
      groups. Both mothers and fathers whose children had been diagnosed within the
      past 2 months reported greater marital dissatisfaction than parents whose
      children were in the other treatment groups. CONCLUSIONS: This finding indicates
      the need for a thorough psychiatric consultation at the time of diagnosis for
      children who have cancer and their families. Ongoing psychosocial support and
      education should have been integral components of the treatment program when
      relapse occurred.

PMID- 12067400
TI  - Changing surgical practice through feedback of performance data.
AB  - BACKGROUND: Changing health care practice is commonly attempted by feedback of
      performance data measured by clinical audit. However, empirical evidence of the
      effectiveness of clinical audit in changing practice is limited. Few studies have
      attempted to evaluate practice development or clinical outcomes within the
      conceptual framework of change theory. Several published studies have used
      passive feedback in an attempt to promote a change in practice. Sending
      information to health care workers on their performance is one of the simplest
      ways of attempting to change performance. AIMS: To evaluate the impact on
      infection rates of the passive feedback of surgical wound infection rate data to
      nurses and surgeons within an empirical rational approach to change, and the
      active feedback of data within a normative re-educative approach to change.
      METHODS: A prospective cohort study over a 3-year period of all surgical patients
      undergoing clean elective surgery (n = 2241). Patients were monitored whilst an
      inpatient and up to 30 days postoperatively by an independent observer to
      determine surgical wound infection rates. The method employed was 'gold standard'
      surveillance, whereby patients were followed up into the community setting.
      INTERVENTIONS: Interventions of feedback and withdrawal of feedback of infection
      rate data and introduction of guidelines for evidence-based surgical practice
      within a change theory framework were monitored by the incidence of infection
      during the periods of the particular intervention. RESULTS: Although the feedback
      of infection rate data impacted on the subsequent infection rates, the reduction
      was not statistically significant. However, a significant reduction in the
      infection rates was achieved following the introduction of guidelines for best
      surgical practice (P < 0.05). CONCLUSIONS: The findings indicate that if change
      in practice is to be achieved by the feedback of performance data, then the
      process of feedback should be active and within a normative re-educative approach
      to change.

PMID- 12067401
TI  - Factors influencing nursing leadership effectiveness in Hong Kong.
AB  - BACKGROUND: Nursing education in Hong Kong has undergone major reform in recent
      years, similar to that in Australia and the United Kingdom (UK), involving the
      introduction of degree level preparation. Although there were some changes in the
      nursing education system, the reform was considered slow. While a combination of
      complex factors contributed to the reform, the effects of nurse leaders was
      instrumental in influencing policy development. AIM: This study investigated the
      factors that influenced the effectiveness of nursing leadership in the reform of
      nursing education in Hong Kong. DESIGN: A case study approach was used. Methods
      of data collection included document search and semi-structured interviews (n =
      27). The time frame of the study extended from the first proposal of nursing
      degree programme in the year 1985 to 2000 by which 200 nursing degree places were
      secured. RESULTS: Situational variables that impacted on leadership effectiveness
      were categorized as barriers and facilitators. Barriers were related to nursing
      professional socialization in a health care system that was dominated by the
      medical profession. Facilitators were related to socio-politic-economical changes
      in the wider environment. CONCLUSION: This study suggests the importance of
      education, positive socialization and unity in promoting nursing leadership
      development.

PMID- 12067402
TI  - Staff nurses' perceptions of supernumerary status compared with rostered service
      for Diploma in Nursing students.
AB  - BACKGROUND/RATIONALE: In the Republic of Ireland, the amount of clinical teaching
      expected of staff nurses has increased substantially in the wake of the transfer
      of nursing education to universities, and the advent of supernumerary status for
      students. A modicum of previous research noted that staff nurses are unclear
      about their role in relation to facilitating the clinical learning of
      supernumerary students. AIMS OF THE PAPER: To explore staff nurses' perceptions
      of their role in the facilitation of learning for university-educated diploma
      students in the clinical area and their attitudes towards these students.
      DESIGN/METHODS: Sixteen staff nurses were interviewed in depth using semi
      structured interviews. Data were analysed qualitatively, using content analysis,
      with the help of the software package NUD*IST. FINDINGS: Among the central themes
      to emerge, upon which this article is focused, was participants' perceptions of
      supernumerary status compared with rostered service for diploma students. Data
      suggested that the rostered status of students was generally favoured by staff
      nurses over and above supernumerary status because, unlike supernumerary
      students, rostered students did not disrupt the existing social structure within
      the clinical setting. Both structuration theory and role theory are drawn upon to
      explain the reproduction of the prevailing social structure, where the
      concentration is on getting through nursing work with little emphasis on the
      supervised learning of supernumerary students. STUDY LIMITATIONS: This study is
      constrained by eliciting only the views of staff nurses. Further studies are
      required of student nurses' experiences of rostered service and supernumerary
      status. CONCLUSIONS: Because staff nurses are part of the system within which
      they work, they need to modify their role to include active student teaching as a
      legitimate component of that role.

PMID- 12067407
TI  - Manipulation of immune responses to Mycobacterium bovis by vaccination with IL-2-
      and IL-18-secreting recombinant bacillus Calmette Guerin.
AB  - Bacillus Calmette Guerin (BCG) has been reported to show variable efficacy as a
      vaccine against tuberculosis. We demonstrated that the secretion of biologically
      active IL-2 (rBCG/IL-2),but not IL-18 (rBCG/IL-18), by BCG improves its ability
      to induce and maintain a strong type 1 immune response in BALB/c mice. rBCG/IL-2
      induced significantly higher Ag-specific proliferative responses, high IFN-gamma
      production and serum titres of IgG2a 16 weeks after vaccination. This immune
      profile was correlated to an increased rate of clearance of non-pathogenic
      mycobacteria (live BCG delivered intranasally). Surprisingly, however,this strong
      type 1 immune profile induced no greater protective immunity against aerosol
      challenge with virulent Mycobacterium bovis than that induced by normal BCG
      (nBCG). By comparison,vaccination with rBCG/IL-18 was found to induce
      significantly less IFN-gamma production in splenic lymphocytes than nBCG. This
      impaired induction of IFN-gamma was correlated to a significantly lower
      protective efficacy against M. bovis challenge, as compared to nBCG. The data
      suggest that manipulation of the immune response to tuberculosis and tuberculosis
      vaccines will require a more complete understanding of the factors that are
      important in generating a protective immune response.

PMID- 12067408
TI  - Competent dendritic cells derived from CD34+ progenitors express CMRF-44 antigen
      early in the differentiation pathway.
AB  - Differentiation of CD34(+) haematopoietic stem cells into functional dendritic
      cells (DC) was investigated using the mAb CMRF-44 and other mAb against DC
      associated markers. GM-CSF mobilized peripheral blood stem cells were obtained
      from healthy donors by leukapheresis. CD34(+) cells were purified using CD34(+)
      positive selection,and subsequent immunomagnetic depletion of CD14 and CD2 cells.
      CD34(+) cells were cultured in medium supplemented with one or more of GM-CSF,TNF
      alpha, IL-4 or IL-6. CMRF-44 Ag expression was monitored by flow cytometry, and
      DC function by allogeneic MLR and tetanus toxoid(TT) presentation assays. CD34(+)
      cells quickly acquired the CMRF-44 Ag when cultured in the presence of TNF-alpha.
      By day 3, more than 50% of the cells were double-positive for CD34 and CMRF-44.
      CD34 expression was gradually lost, so that by day 9, the majority of the cells
      were CD34(-)/CMRF-44(+).GM-CSF and TNF-alpha also induced CD40 expression, and up
      regulation of CD54 and MHC class II on CD34(+) cells; their expression was
      correlated to the CMRF-44 Ag. Day 3 CD34(+)/CMRF-44(+) cells,but not CD34(+)/CMRF
      44(-) cells, become potent APC when cultured further with GM-CSF plus TNF-alpha.
      These CMRF-44(+) cells were potent inducers of Th1-type immune response in the
      primary allogeneic MLR and present TT to autologous CD4(+) T cells. TNF-alpha
      alone is sufficient to induce CMRF-44 expression on CD34(+) cells, but in
      combination with GM-CSF expands the CMRF-44(+) population. CMRF-44 expression
      correlates with DC function and may be a useful early marker for commitment of
      CD34(+) cells to the DC differentiation pathway.

PMID- 12067409
TI  - Proteasome inhibitor MG-132 enhances the expression of interleukin-6 in human
      umbilical vein endothelial cells: Involvement of MAP/ERK kinase.
AB  - Interleukin-6 (IL-6) is a multifunctional cytokine that plays an important role
      in inflammatory reactions. We have addressed the possible regulation of IL-6
      expression by the ubiquitin-protease system in human umbilical vein endothelial
      cells. Cultured endothelial cells were treated with MG-132, a protease inhibitor,
      and the levels of IL-6 mRNA and protein were measured by reverse transcription
      PCR and ELISA. MG-132 increased the expression of IL-6 mRNA and protein;and this
      effect was abolished by the pretreatment of the cells with U0126, an inhibitor of
      MAP or ERK kinases (MEK 1/2). MG-132 treatment was also found to enhance the
      level of phosphorylated MEK 1/2. Treatment of the cells with actinomycin D
      inhibited IL-6 expression in response to MG-132, suggesting the transcriptional
      upregulation of IL-6 under proteasomal inhibition. We conclude that a protease
      inhibitor MG-132 upregulates IL-6 expression in vascular endothelial cells, at
      least in part, through the activation of MEK 1/2.

PMID- 12067410
TI  - Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but
      only minor abnormalities in T(H)1 responses.
AB  - The haematopoietic-specific RhoGTPase, Rac2, has been indirectly implicated in T
      lymphocyte development and function, and as a pivotal regulator of T Helper 1
      (T(H)1) responses. In other haematopoietic cells it regulates cytoskeletal
      rearrangement downstream of extracellular signals. Here we demonstrate that Rac2
      deficiency results in an abnormal distribution of T lymphocytes in vivo and
      defects in T-lymphocyte migration and filamentous actin generation in response to
      chemoattractants in vitro. To investigate the requirement for Rac2 in IFN-gamma
      production and TH1 responses in vivo, Rac2-deficient mice were challenged with
      Leishmania major and immunized with ovalbumin-expressing cytomegalovirus. Despite
      a minor skewing towards a T(H)2 phenotype, Rac2-deficient mice displayed no
      increased susceptibility to L. major infection. Cytotoxic T-lymphocyte responses
      to cytomegalovirus and ovalbumin were also normal. Although Rac2 is required for
      normal T-lymphocyte migration, its role in the generation of T(H)1 responses to
      infection in vivo is largely redundant.

PMID- 12067411
TI  - Trypanosoma cruzi heat-shock protein-70 kDa,alone or fused to the parasite KMP11
      antigen, induces functional maturation of murine dendritic cells.
AB  - We analyse the effect of Trypanosoma cruzi heat-shock protein-70 (HSP70) on the
      maturation of murine dendritic cells (DC)generated from bone marrow precursor
      cells. The results obtained show that HSP70, both alone and fused to the KMP11
      antigen, as well as a HSP70 fragment, is capable of maturing murine DC. Mature DC
      have enhanced expression of IL12, TNF-alpha cytokines, costimulation molecules
      and activation markers, showing a clear increase in the allostimulatory capacity.
      These findings suggest that T. cruzi HSP70 may be a very useful vehicle for
      developing DC-based immunoprophylaxis and therapy against infections.

PMID- 12067412
TI  - Computational immunology: The coming of age.
AB  - The explosive growth in biotechnology combined with major advances in information
      technology has the potential to radically transform immunology in the
      postgenomics era. Not only do we now have ready access to vast quantities of
      existing data, but new data with relevance to immunology are being accumulated at
      an exponential rate. Resources for computational immunology include biological
      databases and methods for data extraction, comparison, analysis and
      interpretation. Publicly accessible biological databases of relevance to
      immunologists number in the hundreds and are growing daily. The ability to
      efficiently extract and analyse information from these databases is vital for
      efficient immunology research. Most importantly, a new generation of
      computational immunology tools enables modelling of peptide transport by the
      transporter associated with antigen processing (TAP), modelling of antibody
      binding sites, identification of allergenic motifs and modelling of T-cell
      receptor serial triggering.

PMID- 12067413
TI  - Immuno-informatics: Mining genomes for vaccine components.
AB  - The complete genome sequences of more than 60 microbes have been completed in the
      past decade. Concurrently, a series of new informatics tools, designed to harness
      this new wealth of information, have been developed. Some of these new tools
      allow researchers to select regions of microbial genomes that trigger immune
      responses. These regions, termed epitopes, are ideal components of vaccines. When
      the new tools are used to search for epitopes, this search is usually coupled
      with in vitro screening methods; an approach that has been termed computational
      immunology or immuno-informatics. Researchers are now implementing these combined
      methods to scan genomic sequences for vaccine components. They are thereby
      expanding the number of different proteins that can be screened for vaccine
      development, while narrowing this search to those regions of the proteins that
      are extremely likely to induce an immune response. As the tools improve, it may
      soon be feasible to skip over many of the in vitro screening steps, moving
      directly from genome sequence to vaccine design. The present article reviews the
      work of several groups engaged in the development of immuno-informatics tools and
      illustrates the application of these tools to the process of vaccine discovery.

PMID- 12067414
TI  - Quantitative approaches to computational vaccinology.
AB  - This article reviews the newly released JenPep database and two new powerful
      techniques for T-cell epitope prediction: (i) the additive method; and (ii) a 3D
      Quantitative Structure Activity Relationships (3D-QSAR) method, based on
      Comparative Molecular Similarity Indices Analysis (CoMSIA). The JenPep database
      is a family of relational databases supporting the growing need of
      immunoinformaticians for quantitative data on peptide binding to major
      histocompatibility complexes and to the Transporters associated with Antigen
      Processing (TAP). It also contains an annotated list of T-cell epitopes. The
      database is available free via the Internet (http://www.jenner.ac.uk/JenPep). The
      additive prediction method is based on the assumption that the binding affinity
      of a peptide depends on the contributions from each amino acid as well as on the
      interactions between the adjacent and every second side-chain. In the 3D-QSAR
      approach, the influence of five physicochemical properties (steric bulk,
      electrostatic potential, local hydrophobicity, hydrogen-bond donor and hydrogen
      bond acceptor abilities) on the affinity of peptides binding to MHC molecules
      were considered. Both methods were exemplified through their application to the
      well-studied problem of peptides binding to the human class I MHC molecule HLA
      A*0201.

PMID- 12067415
TI  - Prediction of promiscuous peptides that bind HLA class I molecules.
AB  - Promiscuous T-cell epitopes make ideal targets for vaccine development. We report
      here a computational system, MULTIPRED, for the prediction of peptide binding to
      the HLA-A2 supertype. It combines a novel representation of peptide/MHC
      interactions with a hidden Markov model as the prediction algorithm. MULTIPREDis
      both sensitive and specific, and demonstrates high accuracy of peptide-binding
      predictions for HLA-A*0201, *0204, and *0205 alleles, good accuracy for *0206
      allele, and marginal accuracy for *0203 allele. MULTIPREDreplaces earlier
      requirements for individual prediction models for each HLA allelic variant and
      simplifies computational aspects of peptide-binding prediction. Preliminary
      testing indicates that MULTIPRED can predict peptide binding to HLA-A2 supertype
      molecules with high accuracy, including those allelic variants for which no
      experimental binding data are currently available.

PMID- 12067417
TI  - Large-scale computational identification of HIV T-cell epitopes.
AB  - Bioinformatics-driven T-cell epitope-identification methods can enhance vaccine
      target selection significantly. We evaluated three unrelated computational
      methods to screen Pol, Gag and Env sequences extracted from the Los Alamos HIV
      database for HLA-A*0201 and HLA-B*3501 T-cell epitope candidates. The hidden
      Markov model predicted 389 HLA-B*3501-restricted candidates from 374 HIV-1 and 97
      HIV-2 sequences. The artificial neural network (ANN) model, and Bioinformatics
      and Molecular Analysis Section (BIMAS) quantitative matrix predictions for A*0201
      yielded 1122 HIV-1 and 548 HIV-2 candidates. The overall sequence coverage of the
      predicted A*0201 T-cell epitopes was 2.7% (HIV-1)and 3.0% (HIV-2). HLA-B*3501
      predicted epitopes covered 0.9% (HIV-1) and 1.4% (HIV-2) of the total sequence.
      Comparison of 890 ANN- and 397 BIMAS-derived HIV-1 A*0201- restricted epitope
      candidates showed that only 13-19% of the predicted and 26% of the experimentally
      confirmed T-cell epitopes were captured by both methods. Extrapolating these
      results, we estimated that at least 247 predicted HIV-1 epitopes are yet to be
      discovered as active A*0201-restricted T-cell epitopes. Adequate comparison and
      combined usage of various predictive bioinformatics methods, rather than
      uncritical use of any single prediction method, will enable cost-effective and
      efficient T-cell epitope screening.

PMID- 12067416
TI  - A combined bioinformatic approach oriented to the analysis and design of peptides
      with high affinity to MHC class I molecules.
AB  - We report on a new method to compute the antigenic degree of peptides from
      available experimental data on peptide binding affinity to class I MHC molecules.
      The methodology is a combination of two strategies at different levels of
      information. The first, at the primary structure level, consists in expressing
      the peptides binding activity as a profile of amino acid contributions, amino
      acid similarity being accounted for by their characteristic physicochemical
      properties and their position within the sequence. The higher level of the
      strategy is based on a meticulous analysis of the contact interface of the
      peptides with the cleft constituting the receptor region of a particular class I
      MHC molecule. Interaction interfaces are inferred by docking the peptide onto the
      receptor groove of the MHC molecule; evaluation of the affinity of the peptide to
      the receptor is then performed by analysis of the electrostatic and hydrophobic
      energies on points of the interaction interface. The result is a robust system
      for analysis of peptide affinity to class I MHC molecules since while the first
      analysis dictates the composition of active sequences at the amino acid level,
      the second translates this information to the atomic level, where the molecular
      interaction can be analyzed in terms of the intrinsic interatomic forces and
      energies. Evaluation results for the methodology are encouraging since high
      affinity peptides are reflected by high scores at both levels of information, and
      are proportionally lower for peptides of medium and lower affinity for which
      interaction surfaces show relatively lower electrostatic complementarity and
      hydrophobic correlation than for the former.

PMID- 12067418
TI  - Selection of escape mutants from immune recognition during HIV infection.
AB  - We present computer simulations of the HIV infection based ona sophisticated
      cellular automata model of the immune response. The infection progresses
      following the well-known three-phase dynamics observed in patients, that is,
      acute, silent and acquired immunodeficiency.Antigenic shift and selection of
      escape viral mutants with low transcription rate explain the long term course of
      the asymptomatic phase, while the immunodeficiency status appears to be the
      consequence of a drastic reduction in T helper cell repertoire.

PMID- 12067419
TI  - Identifying functional relationships among human genes by systematic analysis of
      biological literature.
AB  - BACKGROUND: The availability of biomedical literature in electronic format has
      made it possible to implement automatic text processing methods to expose
      implicit relationships among different documents, and more importantly, the
      functional relationships among the molecules and processes that these documents
      describe. RESULTS: A computational strategy that identifies functionally related
      human genes by detecting the implicit relationships among the publications cited
      under each gene in the Online Mendelian Inheritance in Man (OMIM) was
      implemented. The implementation was based on a substantially modified version of
      the kernel document method. The improvements include assigning a calculated
      weight for a document to indicate its importance in establishing the relationship
      between two documents, and using multiple kernel documents to reflect the
      multiple functions of the same gene. An example of using this strategy to
      identify genes related to the apoptosis pathway in human was given. CONCLUSIONS:
      The results showed that this method can indeed produce meaningful results when
      applied to human genes.

PMID- 12067420
TI  - Estrogen-astrocyte interactions: implications for neuroprotection.
AB  - BACKGROUND: Recent work has suggested that the ovarian steroid 17beta-estradiol,
      at physiological concentrations, may exert protective effects in
      neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and
      acute ischemic stroke. While physiological concentrations of estrogen have
      consistently been shown to be protective in vivo, direct protection upon purified
      neurons is controversial, with many investigators unable to show a direct
      protection in highly purified primary neuronal cultures. These findings suggest
      that while direct protection may occur in some instances, an alternative or
      parallel pathway for protection may exist which could involve another cell type
      in the brain. PRESENTATION OF THE HYPOTHESIS: A hypothetical indirect protective
      mechanism is proposed whereby physiological levels of estrogen stimulate the
      release of astrocyte-derived neuroprotective factors, which aid in the protection
      of neurons from cell death. This hypothesis is attractive as it provides a
      potential mechanism for protection of estrogen receptor (ER)-negative neurons
      through an astrocyte intermediate. It is envisioned that the indirect pathway
      could act in concert with the direct pathway to achieve a more widespread global
      protection of both ER+ and ER- neurons. TESTING THE HYPOTHESIS: We hypothesize
      that targeted deletion of estrogen receptors in astrocytes will significantly
      attenuate the neuroprotective effects of estrogen. IMPLICATIONS OF THE
      HYPOTHESIS: If true, the hypothesis would significantly advance our understanding
      of endocrine-glia-neuron interactions. It may also help explain, at least in
      part, the reported beneficial effects of estrogen in neurodegenerative disorders.
      Finally, it also sets the stage for potential extension of the hypothetical
      mechanism to other important estrogen actions in the brain such as neurotropism,
      neurosecretion, and synaptic plasticity.

PMID- 12067421
TI  - Screening for sequence-specific RNA-BPs by comprehensive UV crosslinking.
AB  - BACKGROUND: Specific cis-elements and the associated trans-acting factors have
      been implicated in the post-transcriptional regulation of gene expression. In the
      era of genome wide analyses identifying novel trans-acting factors and cis
      regulatory elements is a step towards understanding coordinated gene expression.
      UV-crosslink analysis is a standard method used to identify RNA-binding proteins.
      Uridine is traditionally used to radiolabel substrate RNAs, however, proteins
      binding to cis-elements particularly uridine poor will be weakly or not detected.
      We evaluate here the possibility of using UV-crosslinking with RNA substrates
      radiolabeled with each of the four ribonucleotides as an approach for screening
      for novel sequence specific RNA-binding proteins. RESULTS: The radiolabeled RNA
      substrates were derived from the 3'UTRs of the cloned Eg and c-mos Xenopus laevis
      maternal mRNAs. Specific, but not identical, uv-crosslinking signals were
      obtained, some of which corresponded to already identified proteins. A signal for
      a novel 90 kDa protein was observed with the c-mos 3'UTR radiolabeled with both
      CTP and GTP but not with UTP. The binding site of the 90 kDa RNA-binding protein
      was localised to a 59-nucleotide portion of the c-mos 3'UTR. CONCLUSION: That the
      90 kDa signal was detected with RNAs radiolabeled with CTP or GTP but not UTP
      illustrates the advantage of radiolabeling all four nucleotides in a UV-crosslink
      based screen. This method can be used for both long and short RNAs and does not
      require knowledge of the cis-acting sequence. It should be amenable to high
      throughput screening for RNA binding proteins.

PMID- 12067422
TI  - Degradation of transgenic DNA from genetically modified soyabean and maize in
      human intestinal simulations.

PMID- 12067423
TI  - Degradation of transgenic DNA from genetically modified soya and maize in human
      intestinal simulations.
AB  - The inclusion of genetically modified (GM) foods in the human diet has caused
      considerable debate. There is concern that the transfer of plant-derived
      transgenes to the resident intestinal microflora could have safety implications.
      For these gene transfer events to occur, the nucleic acid would need to survive
      passage through the gastrointestinal tract. The aim of the present study was to
      evaluate the rate at which transgenes, contained within GM soya and maize, are
      degraded in gastric and small bowel simulations. The data showed that 80 % of the
      transgene in naked GM soya DNA was degraded in the gastric simulations, while no
      degradation of the transgenes contained within GM soya and maize were observed in
      these acidic conditions. In the small intestinal simulations, transgenes in naked
      soya DNA were degraded at a similar rate to the material in the soya protein.
      After incubation for 30 min, the transgenes remaining in soya protein and naked
      DNA were 52 (sem 13.1) % and 34 (sem 17.5) %, respectively, and at the completion
      of the experiment (3 h) these values were 5 % and 3 %, respectively. In contrast
      to the soya transgene, the maize nucleic acid was hydrolysed in the small
      intestinal simulations in a biphasic process in which approximately 85 % was
      rapidly degraded, while the rest of the DNA was cleaved at a rate similar to that
      in the soya material. Guar gum and tannic acid, molecules that are known to
      inhibit digestive enzymes, did not influence the rate of transgene degradation in
      soya protein. In contrast guar gum reduced the rate of transgene degradation in
      naked soya DNA in the initial stages, but the polysaccharide did not influence
      the amount of nucleic acid remaining at the end of the experiment. Tannic acid
      reduced the rate of DNA degradation throughout the small bowel simulations, with
      21 (sem 5.4) % and 2 (sem 1.8) % of the naked soya DNA remaining in the presence
      and absence of the phenolic acid, respectively. These data indicate that some
      transgenes in GM foods may survive passage through the small intestine.

PMID- 12067424
TI  - Total body phylloquinone and its turnover in human subjects at two levels of
      vitamin K intake.
AB  - The aims of this study were to determine the total body phylloquinone and its
      metabolic turnover in human subjects using a tracer dose of [5-H3]phylloquinone
      containing 4 MBq/mmol. Seven subjects aged 22 to 49 years were given 0.3 microg
      isotopic phylloquinone intravenously on a control diet (75 microg
      phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d.
      Five of these subjects were studied a second time after 3-8 weeks on a low
      vitamin K diet (8 microg/d). The changes in the radioactivity of plasma
      phylloquinone with time were analysed by the method of residuals and fitted to a
      curve composed of two exponential components. The size of the exchangeable body
      pool was calculated by isotope dilution. Plasma phylloquinone levels fell during
      vitamin K restriction but the vitamin K-dependent coagulation factors did not
      change. After injection the first exponential decay curve t1/2 was 1.0 (sd 0.47)
      h in the subjects on the control diet and 0.49 (sd 0.27) h after vitamin K
      restriction. On the control diet, the second exponential t1/2 was 27.6 (sd 124) h
      that did not change on the low-vitamin K diet ( (sd 13.5) h). These results
      indicate that the turnover time for phylloquinone in human subjects is about 1.5
      d. Urinary excretion of 3H-metabolites ranged from 30 % of the administered dose
      on the control diet to 38 % on the restricted diet and had the same turnover rate
      as the second component of the plasma decay curves. The exchangeable body pool of
      phylloquinone declined from about 1.0 microg/kg before restriction to lower
      values after vitamin K restriction. The faecal excretion of phylloquinone and its
      metabolites fell from 32 % of the administered dose on the control diet to 13 %
      on the restricted diet.

PMID- 12067425
TI  - The effect of carbohydrate and fat variation in euenergetic diets on
      postabsorptive free fatty acid release.
AB  - Diet composition and energy content modulate free fatty acid (FFA) release. The
      aim of this study was to evaluate the dose-response effects of euenergetic
      variations in dietary carbohydrate and fat content on postabsorptive FFA release.
      The rate of appearance (Ra) of palmitate was measured by infusion of [2,2
      2H2]palmitate after an overnight fast in six healthy men on three separate
      occasions, i.e. after 7 d on euenergetic control, high-carbohydrate and high-fat
      diets. The protein content and composition was identical for each diet.
      Postabsorptive plasma fatty acid concentrations were not different between the
      high-carbohydrate and control diets (0.36 (se 0.07) v. 0.43 (se 0.04) mmol/l),
      but were increased after the high-fat diet (0.75 (se 0.09) mmol/l, (P<0.01
      compared with the other diets). Ra palmitate was not different between the high
      carbohydrate and control diets (1.36 (se 0.20) v. 1.47 (se 0.15) micromol/kg per
      min). However, Ra palmitate was increased to 2.36 (se 0.26) micromol/kg per min
      after the high-fat diet (P<0.01 compared with the other diets). The fatty acid
      flux and whole-body fat oxidation were not affected by the high-carbohydrate diet
      compared with the control diet, but were increased by 67 and 47 % respectively,
      on the high-fat diet (P<0.01 compared with the other diets). A euenergetic high
      fat diet results in increased postabsorptive FFA release and fat oxidation,
      whereas a euenergetic high-carbohydrate diet does not affect these variables of
      fat metabolism.

PMID- 12067426
TI  - Variation between sheep in renal excretion of [14C]allantoin.
AB  - The objectives of the present study were to investigate the recovery of
      [14C]allantoin in urine of sheep dosed intravenously and degradation of allantoin
      by rumen micro-organisms. The recovery of [14C]allantoin in the urine of eight
      sheep was measured during three periods in two experiments. Individual values of
      [14C]allantoin recovery varied from 66 to 95 % (mean value 83 (se 1.6) %). The
      recovery of [14C]allantoin showed no relation to the level of feed intake. There
      was some evidence that glomerular filtration rate was an important factor
      affecting the amount of urinary allantoin recovered in one experiment. Incomplete
      recovery of plasma [14C]allantoin in the urine indicated losses of plasma
      [14C]allantoin via non-renal routes. This is supported by the disappearance of
      14C from rumen contents incubated in vitro with [14C]allantoin for 48 h (88 %)
      and the presence of 14C in saliva in vivo from sheep sampled after dosing with
      [14C]allantoin. However, the amount of 14C activity in the saliva was very low
      (equivalent to only 1.5 % of the total dose in sheep producing saliva at a rate
      of 15 litres/d). The proportion of renal and non-renal excretion of purine
      derivatives was found to be unpredictable both between and within individual
      animals. The factors responsible for this variability need to be identified, and
      existing models of excretion of purine derivatives may need to be modified
      accordingly to improve their accuracy of prediction. A single intravenous
      injection of [4,5-14C]allantoin provides a simple alternative to infusion methods
      used to measure the proportion of plasma allantoin excreted in the urine of
      sheep. Using this method it may be feasible to validate PD excretion models in
      other ruminant livestock.

PMID- 12067427
TI  - Quantitative kinetics of glucose appearance and disposal following a 13C-labelled
      starch-rich meal: comparison of male and female subjects.
AB  - In the UK, starch contributes up to 25 % of energy intake in adults (). The
      present study investigated the acute response to a starchy meal on whole-body
      glucose metabolism and assessed insulin sensitivity in men compared with women.
      Low insulin sensitivity has been postulated to pre-dispose individuals to a
      cluster of associated abnormalities known to increase the risk of CHD. Metabolic
      responses to a 13C-labelled meal were determined in conjunction with a primed
      continuous infusion of d-[6,6-2H]glucose in groups of healthy age- and BMI
      matched men and women. Peripheral plasma glucose disposal (Gd) was computed using
      non-steady state kinetics in a single compartment model, simultaneously with
      determination of whole-body net glucose oxidation by indirect calorimetry.
      Insulin sensitivity was derived using cumulative Gd as the dependent variable,
      and time and the integrated insulin concentration as independent variables. The
      female group had the higher fractional rate of glucose appearance in plasma from
      starch (P=0.019) immediately after ingestion. Females also had a higher rate of
      plasma Gd and a significantly higher insulin-dependent Gd (6.8 v. 5.6 microg
      glucose/(min.kg) per pmol insulin, P<0.05) compared with the males. A smaller
      absolute pool of endogenous glucose in females allowed the rate of exogenous
      13CO2 production to be significantly higher in the females (P=0.007)
      corresponding also to a significantly higher (P<0.05) carbohydrate oxidation rate
      obtained by indirect calorimetry. The present study suggests that during the
      ingestion of a starchy meal, females exhibit higher glucose flux and greater
      whole-body insulin sensitivity than males.

PMID- 12067428
TI  - Dietary supplementation with vitamin E modulates avian intestinal immunity.
AB  - The effect of dietary vitamin E on immunoglobulin A (IgA) antibody production,
      which acts as the first line of defence at the intestinal mucosa, has not been
      evaluated in chickens. In the present study the impact of the inclusion of
      supplementary levels of vitamin E to the diet, on total and antigen-specific IgA
      antibody titres, T-cell subsets and Ia+ cells, was assessed. From hatching,
      chickens received a maize-based diet which was supplemented with either 25, 250,
      2500 or 5000 mg dl-alpha-tocopherol acetate/kg. Primary immunisation with tetanus
      toxoid (T. toxoid) emulsified in a vegetable oil-in-water adjuvant was
      administered by the intraperitoneal route at 21 d of age. At 35 d of age all
      birds received an oral booster vaccination of T. toxoid. Significantly higher
      total IgA antibody titres were present in the day 42 intestinal scrapings of
      birds receiving the 5000 mg/kg vitamin E-supplemented diet (VESD) (P=0.05) and a
      notable increase was observed in birds receiving the 250 mg/kg VESD (P=0.06). At
      days 21 and 42 total serum IgA antibody titres of birds receiving the 250 mg/kg
      VESD was significantly higher (P<0.05) than the control birds. Following
      immunisation with T. toxoid, birds receiving the 250 and the 5000 mg/kg VESD had
      elevated anti-T. toxoid IgA antibody titres in final day intestinal scrapings,
      which, for the latter group was statistically significant (P=0.02). Both of these
      groups also demonstrated increased titres of anti-T. toxoid IgA in the serum at
      day 42. Birds receiving the 250 mg/kg VESD exhibited a notable increase in the
      percentage of T-helper cells and Ia+ cells in peripheral blood on day 26. The
      results illustrate the potential for some levels of dietary vitamin E
      supplementation to act as an immunomodulator of total and antigen-specific IgA
      antibody.

PMID- 12067429
TI  - Insulin-like growth factor-I and analogues increase growth in artificially-reared
      neonatal pigs.
AB  - Exogenous insulin-like growth factor (IGF)-I has been shown to increase growth
      rate in neonatal pigs while an analogue of IGF-I, long arginine (LR3) IGF-I, has
      been shown to be more potent than IGF-I in the rat. Therefore, two studies were
      conducted to determine whether IGF-I and LR3IGF-I increase growth in the
      artificially-reared neonatal pig. Expt 1 involved forty-two (2 kg initial weight)
      pigs infused with either control, IGF-I (2, 4 or 8 microg/h) or LR3IGF-I (2, 4 or
      8 microg/h) infusions for 8 d. Pigs were weighed and then offered 1.7 MJ (gross
      energy) milk replacer/kg0.75 per d. Expt 2 involved eighteen pigs (2 kg initial
      weight) treated with control saline, IGF-I (8 microg/h) or LR3IGF-I (8 microg/h)
      infusions. After 9 d an additional pump was inserted to increase the infusion
      rates of each of the growth factors (16 microg/h) for a further 9 d. Cows' milk
      was provided ad libitum. In Expt 1 there was no overall effect of growth factors
      on daily weight gain or slaughter weight. However, milk intake was greater in
      pigs infused with growth factors (909 v. 867 g/d, P=0.027), with an apparently
      greater milk intake by the pigs infused with IGF-I compared with LR3IGF-I (920 v.
      898 g/d, P=0.12). Infusion of LR3IGF-I decreased plasma IGF-I concentrations, but
      had no effect on plasma IGF-II concentrations. In Expt 2, neither IGF-I nor
      LR3IGF-I infusion had any effect upon daily weight gain over the first 9 d of the
      study. However, over the second 9 d of the study, daily weight gain was increased
      in LR3IGF-I-infused pigs (457 v. 386 g/d, P<0.01), but not in pigs infused with
      IGF-I (413 v. 386 g/d, P=0.15). Milk intake was not different during the first 9
      d of the study but was significantly greater in pigs infused with growth factors
      over the second half of the study (3407 v. 2905 g/d, P<0.01). Plasma IGF-binding
      protein-3 concentrations were highly correlated (R=0.85) with average daily gain
      over the 3 d preceding blood sampling. In conclusion, exogenous IGF-I and
      particularly LR3IGF-I can increase growth rate and milk intake in artificially
      reared pigs fed ad libitum but not in limit-fed piglets.

PMID- 12067430
TI  - Fifteen-year time trends in energy and macronutrient intake in German children
      and adolescents: results of the DONALD study.
AB  - The DONALD study (Dortmund Nutritional and Anthropometric Longitudinally Designed
      study) gives the opportunity to evaluate long-term food and nutrient intake data
      on the basis of 3 d weighed dietary records of infants, children and adolescents
      since 1985. In this paper, we examine changes in energy and macronutrient intakes
      (protein, fat, saturated, mono- and polyunsaturated fatty acids, carbohydrates
      and added sugars) of 795 2-18-year-old subjects between 1985 and 2000 (4483
      records). No significant changes in intakes of energy and of protein,
      polyunsaturated fatty acids and added sugars (as % energy intake, E %) were
      found. Fat intake decreased significantly in all age groups (between -0.20 and 
      0.26 E %/year), as well as intake of saturated fatty acids (between -0.11 and 
      0.14 E %/year) and monounsaturated fatty acids (between -0.07 and -0.014 E
      %/year). This decline was compensated for by a significant increase in
      carbohydrate intake (between +0.18 and +0.27 E %/year). The changes in
      macronutrient intake were mainly due to a decreased consumption of fats-oils
      (between -0.29 and -1.26 g/year) and meat-fish-eggs (between -0.21 and -2.92
      g/year), whereas consumption of bread-cereals (between +0.12 and +2.42 g/year)
      and potatoes-pasta-rice (between +0.15 and +2.26 g/year) increased slightly.
      However, since recommended fat intake and fatty acid composition was not reached
      at the end of the study period by far, further efforts will be necessary to
      improve macronutrient composition and to stabilize favourable dietary habits.

PMID- 12067431
TI  - Intake and sources of phylloquinone (vitamin K1): variation with socio
      demographic and lifestyle factors in a national sample of British elderly people.
AB  - Intake and sources of phylloquinone (vitamin K1) were examined according to socio
      demographic and lifestyle factors in free-living British people aged 65 years and
      over, from the 1994-5 National Diet and Nutrition Survey. Complete 4-d weighed
      dietary records were obtained from 1152 participants living in private
      households. Using newly-available, mainly UK-specific food content data, the
      weighted geometric mean intake of phylloquinone was estimated at 65 (95 % CI 62,
      67) microg/d for all participants, with higher intakes in men than in women (70
      v. 61 microg/d respectively, P<0.01). The mean nutrient densities of
      phylloquinone intake were 9.3 and 10.5 microg/MJ for men and women respectively
      (P<0.01), after adjusting for age group, region and smoking status. Of all the
      participants, 59 % had phylloquinone intakes below the current guideline for
      adequacy of 1 microg/kg body weight per d. Participants aged 85 years and over,
      formerly in manual occupations, or living in Scotland or in northern England
      reported lower phylloquinone intakes than their comparative groups. Overall,
      vegetables contributed 60 % of total phylloquinone intake, with cooked green
      vegetables providing around 28 % of the total. Dietary supplements contributed
      less than 0.5 % of phylloquinone intake. Participants living in northern England
      or in Scotland, in particular, derived less phylloquinone from vegetables than
      those living in southern England.

PMID- 12067432
TI  - Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in
      a national sample of British elderly people.
AB  - Plasma phylloquinone (vitamin K1) concentration was examined according to season,
      socio-demographic and lifestyle factors and phylloquinone intake in a nationally
      representative sample of British people aged 65 years and over from the 1994-5
      National Diet and Nutrition Survey. Values for both plasma phylloquinone
      concentration and phylloquinone intake were available from 1076 participants (561
      men, 515 women). Eight hundred and thirty-four were living in private households,
      242 in residential or nursing homes. Weighted geometric mean plasma phylloquinone
      concentrations were 0.36 (inner 95% range [corrected] 0.06, 2.01) and 0.24 (inner
      94% range [corrected] 0.06, 0.96) nmol/l in free-living and institution samples
      respectively. Plasma phylloquinone concentrations did not generally differ
      between men and women, although values in free-living people were significantly
      lower during autumn and winter (October to March). Plasma phylloquinone
      concentration was not significantly associated with age. Plasma phylloquinone
      concentrations were positively correlated with phylloquinone intake in free
      living men and women (r 0.18 and 0.30 respectively, both P<0.001). Stepwise
      multiple regression analysis found that 11 % of the variation in plasma
      phylloquinone concentration was explained by phylloquinone intake, season and
      plasma triacylglycerol concentration. After adjustment for age and corresponding
      nutrient intakes, plasma phylloquinone concentration was significantly associated
      (each P<0.01) with plasma concentrations of triacylglycerol, cholesterol, retinol
      and 25-hydroxyvitamin D in free-living women but not men, and with plasma
      concentrations of carotenes, alpha- and gamma-tocopherols and lutein in free
      living men and women. The possibility of concurrent low fat-soluble vitamin
      status in elderly populations may be a cause for concern.

PMID- 12067433
TI  - Comparison of the TriTrac-R3D accelerometer and a self-report activity diary with
      heart-rate monitoring for the assessment of energy expenditure in children.
AB  - Determining total energy expenditure (EE) in children under free-living
      conditions has become of increasingly clinical interest. The aim of this study
      was to compare three different methods to assess EE triaxial accelerometry
      (TriTrac-R3D; Professional Products, Division of Reining International, Madison,
      WI, USA), activity diary and heart-rate (HR) monitoring combined with indirect
      calorimetry (IC). Twenty non-obese children and adolescents, aged 5.5 to 16.0
      years, participated in this study. Results from the three methods were collected
      simultaneously under free-living conditions during the same 24 h schoolday
      period. Neither activity diary (5904 (sd 1756) kJ) nor the TriTrac-R3D (6389 (sd
      979) kJ) showed statistical differences in 24 h total EE compared with HR
      monitoring (5965 (sd 1911) kJ). When considering different physical activity (PA)
      periods, compared with HR monitoring, activity diary underestimates total EE
      during sedentary periods (P<0.001) and overestimates total EE and PA-EE during PA
      periods (P<0.001) because of the high energy cost equivalence of activity levels.
      The TriTrac-R3D, compared with HR monitoring, shows good agreement for assessing
      PA-EE during PA periods (mean difference +0.25 (sd 1.9) kJ/min; 95 % CI for the
      bias -0.08, 0.58), but underestimates PA-EE and it does not show good precision
      during sedentary periods (-0.87 (sd 1.4) kJ/min, P<0.001). Correlation between
      the vector magnitude generated by the TriTrac-R3D accelerometer and EE of
      activities derived from HR monitoring is high. When compared with the HR method,
      the TriTrac-R3D and activity diary are not systematically accurate and must be
      carefully used for the assessment of children's EE depending on the purpose of
      each study.

PMID- 12067434
TI  - Rapid screening for high-titer retroviral packaging cell lines using an in situ
      fluorescence assay.
AB  - The production of high-titer recombinant retrovirus is a major determinant of the
      efficiency of target cell transduction. Titer assessment for producer clones that
      contain vectors encoding proteins that can be detected using fluorescence is
      typically performed by flow cytometry. However, this method is both costly and
      labor intensive, severely limiting the number of clones that can be screened for
      each construct. In this report we describe a rapid, high-throughput screening
      method for viral quantitation of producer clone supernatant on target cells using
      a 96-well format. Plates were assayed using a multichannel fluorescent reader to
      determine the percentage of target cells expressing green (EGFP), cyan (ECFP),
      yellow (EYFP) or red (DsRed) fluorescent reporter genes, or their combinations.
      The relative fluorescence counts of target cells incubated with viral supernatant
      from each packaging cell clone correlated with the level of transduction, and
      hence, viral titer. Correlation of cell fluorescence between the fluorescent
      plate reader assay and flow cytometric assessment was high (r(2) = 0.96).
      Independent detection of different fluorescent reporters enabled multiplex assays
      to be performed. Simultaneous cell density analysis using alamarBlue fluorescence
      was proportional to cell number per well (r(2) = 1.0). In situ titer assessment
      of 66 FLYRD packaging cells encoding the EGFP reporter gene identified clones
      (>10(7) colony forming units per milliliter [CFU/ml]) that provided titers up to
      sevenfold over the parent population. The application of this rapid, high
      throughput screening method overcomes many limitations imposed by the current
      flow cytometric screening method. This robust assay maximizes the chance of
      identifying rare high-titer packaging clones and offers a further opportunity to
      optimize gene transfer protocols.

PMID- 12067435
TI  - Caspase-8 gene therapy using the human telomerase reverse transcriptase promoter
      for malignant glioma cells.
AB  - Telomerase is a distinctive candidate for targeted gene therapy of malignant
      gliomas, because the vast majority of malignant gliomas express telomerase
      activity while normal brain tissues do not. Recently, we developed a telomerase
      specific expression system of caspase-8 gene using the promoter of the human
      telomerase reverse transcriptase (hTERT) gene. However, the transcriptional
      activity of hTERT-181 promoter (a 181-base pair [bp] region upstream of the
      transcription start site) was relatively lower in malignant glioma cells than in
      other tumors such as prostate cancer cells. To establish the hTERT/caspase-8
      construct as a novel therapy for malignant gliomas, we need to increase the
      transcriptional activity of the hTERT promoter in malignant glioma cells. In the
      present study, we demonstrate that the transcriptional activity of hTERT-378
      promoter (a 378-bp region) was 2- to 40-fold higher in hTERT-positive malignant
      glioma cells (A172, GB-1, T98G, U87-MG, U251-MG, and U373-MG) than that of hTERT
      181. We further demonstrate that by using the hTERT-378/caspase-8 construct,
      apoptosis was restricted to malignant glioma cells, and was not seen in
      astrocytes or fibroblasts lacking hTERT. Moreover, the growth of subcutaneously
      established U373-MG tumors in mice was significantly inhibited by seven daily
      intratumoral injections of hTERT-378/caspase-8 construct and its inhibitory
      effect persisted during 3 additional weeks without additional treatment. These
      results suggest that the telomerase-specific expression of caspase-8 under hTERT
      378 promoter is a novel targeting approach for the treatment of telomerase
      positive malignant gliomas.

PMID- 12067436
TI  - Enhanced inhibition of human immunodeficiency virus type 1 replication by novel
      lentiviral vectors expressing human immunodeficiency virus type 1 envelope
      antisense RNA.
AB  - We have developed optimized versions of a conditionally replicating human
      immunodeficiency virus type 1 (HIV-1)-based lentiviral vector for gene therapy of
      HIV-1 infection. These vectors target HIV-1 RNAs containing sequences of the
      envelope gene by expressing a 1-kb fragment of the HIV-1 Tat/Rev intron in the
      antisense orientation. Expression of the envelope antisense gene (envAS) was
      evaluated under the control of different internal promoters such as the human
      phosphoglycerate kinase (PGK) promoter, the human EF1-alpha promoter, and the U3
      region of the SL3 murine leukemia virus. The U3-SL3 promoter transactivates
      transcription from the vector HIV-1 LTR and drives higher expression levels of
      envAS-containing RNAs than other promoters in T-cell lines. The effect of other
      vector structural features was also evaluated. We found that the central
      polypurine tract and central termination sequence (cPPT) produce a small increase
      in vector infectivity of 2-fold to 3-fold and results in a 10-fold higher
      inhibition of wild-type viral replication in challenge experiments. The woodchuck
      hepatitis posttranscriptional regulatory element (WPRE) does not increase the
      cytoplasmic levels of envAS mRNA in T-cell lines. We observed that SupT1 and
      primary CD4(+) T cells transduced with these vectors showed high inhibition of
      HIV-1 replication, suppression of syncitium formation, and increased cell
      viability when infected with several HIV-1 laboratory strains. Our results
      suggest that higher vector copy number and increased levels of envAS RNA
      expression contribute to block replication of divergent strains of HIV-1.

PMID- 12067437
TI  - Retrovirus-mediated WASP gene transfer corrects Wiskott-Aldrich syndrome T-cell
      dysfunction.
AB  - The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by
      thrombocytopenia, eczema, and immunodeficiency. At present, the only definitive
      therapy for the disease is allogeneic bone marrow transplantation (BMT). Because
      of the frequent lack of suitable donors and the potential severe complications
      associated with BMT, the development of gene-based therapeutic strategies for WAS
      is highly desirable. To study whether corrective gene transfer into WAS T cells
      can lead to restoration of the immunologic defects of WAS, a retroviral vector
      expressing the WAS protein (WASP) gene was used to transduce human T-lymphotropic
      virus type 1-transformed T-cell lines and primary T lymphocytes from patients
      with WAS. After transduction, WAS T cells showed levels of WASP expression
      similar to those found in cells from normal individuals. In addition, the
      reconstituted WASP interacted in vitro with proteins containing SH3 domain such
      as Grb2, PLC-gamma1, and Fyn, each of which are connected to signaling pathways
      linked to the actin cytoskeleton. Furthermore, after CD3 cross-linking,
      transduced WAS T lines showed improvement of actin polymerization and T-cell
      receptor/CD3 down-regulation. More importantly, primary WAS T lymphocytes
      transduced with WASP acquired the ability to proliferate in response to anti-CD3
      stimulation. These findings suggest that biologic defects of WAS T cells can be
      corrected in vitro by retrovirus-mediated gene transfer and pose the basis for
      future investigation of gene therapy as treatment for WAS.

PMID- 12067438
TI  - Increased survival and function of SOD1 mice after glial cell-derived
      neurotrophic factor gene therapy.
AB  - Amyotrophic lateral sclerosis (ALS) is caused by a progressive degeneration of
      motor neurons. The cause of sporadic ALS is not known, but 1-2% of all cases are
      familial and caused by mutations in the copper-zinc superoxide dismutase (SOD1)
      gene. Transgenic SOD1 mice serve as a transgenic mouse model for these cases.
      Glial cell-derived neurotrophic factor (GDNF) has a potent trophic effect on
      motor neurons. Clinical trials in which growth factors have been systemically
      administered to ALS patients have not been effective, owing in part to the short
      half-life of these factors and their low concentrations at target sites. Gene
      transfer of therapeutic factors to motor neurons and/or their target cells, such
      as muscle, may overcome these problems. Previously, we and others have shown that
      intramuscularly administered adenovirus vector (AVR) results in foreign gene
      expression not only in muscle cells, but also in relevant motor neurons in the
      spinal cord, because of retrograde axonal transport. In this study we utilized an
      AVR to introduce GDNF into muscles of neonatal SOD1 mice. We showed that AVR
      mediated GDNF expression delayed the onset of disease by 7 +/- 8 days (mean +/-
      SD), prolonged survival by 17 +/- 10 days, and delayed the decline in motor
      functions (as determined on a rotating rod) by 7-14 days. These results
      demonstrate that gene delivery to muscle and motor neurons has the potential to
      treat devastating neurodegenerative diseases such as ALS.

PMID- 12067439
TI  - Efficient oncoretroviral transduction of extended long-term culture-initiating
      cells and NOD/SCID repopulating cells: enhanced reconstitution with gene-marked
      cells through an ex vivo expansion approach.
AB  - Recent developments of surrogate assays for human hematopoietic stem cells (HSC)
      have facilitated efforts at improving HSC gene transfer efficiency. Through the
      use of xenograft transplantation models, such as nonobese diabetic/severe
      combined immunodeficiency (NOD/SCID) mice, successful oncoretroviral gene
      transfer to transplantable hematopoietic cells has been achieved. However,
      because of the low frequency and/or homing efficiency of SCID repopulating cells
      (SRC) in bone marrow (BM), studies have primarily focused on cord blood (CB). The
      recently developed extended (> 60 days) long-term culture-initiating cell (ELTC
      IC) assay detects an infrequent and highly quiescent candidate stem cell
      population in BM as well as CB of the CD34(+)CD38(-) phenotype. Although these
      characteristics suggest that ELTC-IC and SRC might be closely related, attempts
      to oncoretrovirally transduce ELTC-IC have been unsuccessful. Here, recently
      developed conditions (high concentrations of SCF + FL + Tpo in serum-free medium)
      supporting expansion of BM CD34(+)CD38(-) 12 week ELTC-IC promoted efficient
      oncoretroviral transduction of BM and CB ELTC-IC. Although SRC can be transduced
      with oncoretroviral vectors, this is frequently associated with loss of
      reconstituting activity, posing a problem for development of clinical HSC gene
      therapy. However, previous attempts at expanding transduced HSC posttransduction
      resulted in compromised rather than improved gene marking. Utilizing conditions
      promoting cell divisions and transduction of ELTC-IC we show that although 5 days
      of ex vivo culture is sufficient to obtain maximum gene transfer efficiency to
      SRC, extension of the expansion period to 12 days significantly enhances
      multilineage reconstitution activity of transduced SRC, supporting the
      feasibility of improving gene marking through ex vivo expansion.

PMID- 12067440
TI  - The epidermis as a bioreactor: topically regulated cutaneous delivery into the
      circulation.
AB  - Previous studies have documented that the skin can be used as a bioreactor to
      produce proteins for systemic release to treat diseases. A gene-switch system has
      been developed that allows regulated expression of therapeutic genes. To
      determine whether this system could be used in the skin, we developed a
      transgenic mouse model in which expression of a therapeutic gene could be
      topically induced in epidermal keratinocytes. After a single induction, high
      levels of the therapeutic protein, human growth hormone (hGH), were released from
      keratinocytes into the circulation. The serum levels of hGH were dependent on the
      amount of inducer applied, and repeated induction resulted in increased weight
      gain by transgenic versus control mice. Furthermore, physiological levels of hGH
      were detected in the serum of nude mice after topical induction of small
      transgenic skin grafts. These results clearly demonstrate the feasibility of
      using the gene-switch system to regulate the delivery of therapeutic proteins
      into the circulation via genetically modified keratinocytes.

PMID- 12067441
TI  - Effect of injecting primary myoblasts versus putative muscle-derived stem cells
      on mass and force generation in mdx mice.
AB  - It is well established that the injection of normal myoblasts or of muscle
      derived stem cells (MDSCs) into the muscle of dystrophin-deficient mdx mice
      results in the incorporation of a number of donor myoblasts into the host muscle.
      However, the effect of the injected exogenous cells on mdx muscle mass and
      functional capacity has not been evaluated. This study evaluates the mass and
      functional capacity of the extensor digitorum longus (EDL) muscles of adult, male
      mdx mice that received intramuscular injections of primary myoblasts or of MDSCs
      (isolated by a preplating technique; Qu, Z., Balkir, L., van Deutekom, J.C.,
      Robbins, P.D., Pruchnic, R., and Huard, J., J. Cell Biol. 1998;142:1257-1267)
      derived from normal mice. Evaluations were made 9 weeks after cell
      transplantation. Uninjected mdx EDL muscles have a mass 50% greater than that of
      age-matched C57BL/10J (normal) EDL muscles. Injections of either primary
      myoblasts or MDSCs have no effect on the mass of mdx EDL muscles. EDL muscles of
      mdx mice generate 43% more absolute twitch tension and 43% less specific tetanic
      tension then do EDL muscles of C57BL/10J mice. However, the absolute tetanic and
      specific twitch tension of mdx and C57BL/10J EDL muscles are similar. Injection
      of either primary myoblasts or MDSCs has no effect on the absolute or specific
      twitch and tetanic tensions of mdx muscle. Approximately 25% of the myofibers in
      mdx EDL muscles that received primary myoblasts react positively with antibody to
      dystrophin. There is no significant difference in the number of dystrophin
      positive myofibers when MDSCs are injected. Regardless of the source of donor
      cells, dystrophin is limited to short distances (60-900 microm) along the length
      of the myofibers. This may, in part, explain the failure of cellular therapy to
      alter the contractile properties of murine dystrophic muscle.

PMID- 12067442
TI  - Efficient transduction of dendritic cells and induction of a T-cell response by
      third-generation lentivectors.
AB  - In order to induce a therapeutic T lymphocyte response, recombinant viral
      vaccines are designed to target professional antigen-presenting cells (APC) such
      as dendritic cells (DC). A key requirement for their use in humans is safe and
      efficient gene delivery. The present study assesses third-generation lentivectors
      with respect to their ability to transduce human and mouse DC and to induce
      antigen-specific CD8+ T-cell responses. We demonstrate that third-generation
      lentivectors transduce DC with a superior efficiency compared to adenovectors.
      The transfer of DC transduced with a recombinant lentivector encoding an
      antigenic epitope resulted in a strong specific CD8+ T-cell response in mice. The
      occurrence of lower proportions of nonspecifically activated CD8+ cells suggests
      a lower antivector immunity of lentivector compared to adenovector. Thus,
      lentivectors, in addition to their promise for gene therapy of brain disorders
      might also be suitable for immunotherapy.

PMID- 12067443
TI  - In vivo-targeted gene delivery using antibody-based nonviral vector.
AB  - Tissue-specific gene transfer remains one of the main challenges to deliver genes
      into designated and/or disseminated cells. We have previously shown successful
      gene transfer with a nonviral gene delivery system based on the simple chemical
      conjugation of plasmid DNA with antibody. However, this approach was hampered by
      low efficiency due to the poor translocation rate of DNA to the nucleus. To
      improve this approach, we have modified our vector by introducing noncovalent
      binding between the antibody and DNA, allowing the possibility to introduce
      different important molecules. The noncovalent association was achieved with
      neutravidin and biotinylated components: (1) biotinylated antibodies; (2) a
      biotinylated hemagglutinin fusogenic peptide of influenza virus to favor
      endosomal escape; and (3) biotinylated histone H1 to compact, protect, and
      associate DNA to the complex. We report here that this delivery system can be
      internalized by tumor cells targeted by a specific monoclonal antibody, permits
      the protection of the transfected DNA, and allows its subsequent transfer into
      the nucleus after escape from the endosomal compartment. We also demonstrate
      that, in vitro, gene transfer with this vector showed much higher reporter
      activity in cells (15 vs. 0.5%) and a stronger production of murine interleukin 2
      as compared with our previous vector. In vivo, a single intravenous injection of
      the vector containing an antibody directed to the G250 renal cell carcinoma
      associated antigen led to beta-galactosidase expression in engrafted tumor
      bearing G250 but not in G250-negative tumor or in other tissues. Altogether,
      these results indicate that our antibody-based vector is suitable to promote gene
      delivery in vitro and in vivo in tumor cells.

PMID- 12067444
TI  - Adeno-associated viral vectors penetrate human solid tumor tissue in vivo more
      effectively than adenoviral vectors.
AB  - The transduction efficiencies of adeno-associated viral vectors (AAV, serotype 2)
      and adenovirus vectors (ADV, serotype 5) were examined in three different models
      of cancer. First, we used flow cytometry to quantitate AAV-GFP or ADV-GFP
      transduction in 13 cell lines derived from malignant tissue (6 gliomas, 6 mammary
      cancers, and 1 leukemia). These experiments showed variable transduction
      efficiency (0%-81%) between the cell lines, with ADV being more effective
      compared to AAV in 9 of 13 cell lines. Second, spheroids prepared from human
      glioblastomas were infected with ADV or AAV expressing GFP or lacZ cassettes, and
      after 2 weeks, uniform reporter gene expression was observed on the spheroid.
      Whereas AAV produced consistent transduction throughout the spheroids, ADV
      infection was mainly limited to the outer cell layers of the spheroids,
      suggesting that AAV were more efficient at penetrating solid tumor tissue. Third,
      human biopsies from glioblastoma multiforme patients were xenografted into nude
      rats and grown for 4 weeks followed by viral vector injection. Combined use of
      high-resolution magnetic resonance imaging (MRI) and histologic analysis allowed
      the identification of transduced cells and their spatial distribution within the
      tumors. AAV-mediated transgene expression was observed in cell clusters through
      the entire tumor, while ADV-mediated transduction was restricted to cells at the
      tumor periphery. Thus, while AAV and ADV vectors may infect tumor-derived cell
      lines to a similar degree, AAV penetrated glioblastoma spheroids and xenografts
      more efficiently compared to ADV vectors. These results suggest that AAV may be
      suitable for therapeutic gene delivery to malignant tumors.

PMID- 12067445
TI  - Clinical protocol. A phase II study: efficacy of the gene therapy of the MVA E2
      recombinant virus in the treatment of precancerous lesions (NIC I and NIC II)
      associated with infection of oncogenic human papillomavirus.

PMID- 12067447
TI  - Cell death mechanisms in neurodegeneration.
AB  - Progressive cell loss in specific neuronal populations often associated with
      typical cytoskeletal protein aggregations is a pathological hallmark of
      neurodegenerative disorders, but the nature, time course and molecular causes of
      cell death and their relation to cytoskeletal pathologies are still unresolved.
      Apoptosis or alternative pathways of cell death have been discussed in
      Alzheimer's disease and other neurodegenerative disorders. Apoptotic DNA
      fragmentation in human brain as a sign of neuronal injury is found too frequent
      as to account for continuous neuron loss in these slowly progressive processes.
      Morphological studies revealed extremely rare apoptotic neuronal death in
      Alzheimer's disease but yielded mixed results for Parkinson's disease and other
      neurodegenerative disorders. Based on recent data in human brain, as well as in
      animal and cell culture models, a picture is beginning to emerge suggesting that,
      in addition to apoptosis, other forms of programmed cell death may participate in
      neurodegeneration. Better understanding of the molecular players will further
      elucidate the mechanisms of cell death in these disorders and their relations to
      cytoskeletal abnormalities. Susceptible cell populations in a proapoptotic
      environment show increased vulnerability towards multiple noxious factors
      discussed in the pathogenesis of neurodegeneration. In conclusion, although many
      in vivo and in vitro data are in favor of apoptosis involvement in
      neurodegenerative processes, there is considerable evidence that very complex
      events may contribute to neuronal death with possible repair mechanisms, the
      elucidation of which may prove useful for future prevention and therapy of
      neurodegenerative disorders.

PMID- 12067448
TI  - Contribution of apoptotic cell death to renal injury.
AB  - Cell number abnormalities are frequent in renal diseases, and range from the
      hypercellularity of postinfectious glomerulonephritis to the cell depletion of
      chronic renal atrophy. Recent research has shown that apoptosis and its
      regulatory mechanisms contribute to cell number regulation in the kidney. The
      role of apoptosis ranges from induction to repair and progression of renal
      injury. Death ligands and receptors, such as TNF and FasL, proapoptotic and
      antiapoptotic Bcl-2 family members and caspases have all been shown to
      participate in apoptosis regulation in the course of renal injury. These proteins
      represent potential therapeutic targets, which should be further explored.

PMID- 12067449
TI  - Problems and solutions in myoblast transfer therapy.
AB  - Duchenne muscular dystrophy is a severe X-linked neuromuscular disease that
      affects approximately 1/3500 live male births in every human population, and is
      caused by a mutation in the gene that encodes the muscle protein dystrophin. The
      characterization and cloning of the dystrophin gene in 1987 was a major
      breakthrough and it was considered that simple replacement of the dystrophin gene
      would ameliorate the severe and progressive skeletal muscle wasting
      characteristic of Duchenne muscular dystrophy. After 20 years, attempts at
      replacing the dystrophin gene either experimentally or clinically have met with
      little success, but there have been many significant advances in understanding
      the factors that limit the delivery of a normal dystrophin gene into dystrophic
      host muscle. This review addresses the host immune response and donor myoblast
      changes underlying some of the major problems associated with myoblast-mediated
      dystrophin replacement, presents potential solutions, and outlines other novel
      therapeutic approaches.

PMID- 12067450
TI  - Detection of human papillomavirus gene sequences in cell lines derived from
      laryngeal tumors.
AB  - The role of Human Papillomaviruses (HPV) in laryngeal carcinomas has been studied
      with conflicting results. To evaluate the etiologic relationship between HPV
      infection and epithelial malignancy of the larynx we studied five laryngeal
      carcinoma cell lines obtained from patients undergoing surgery for laryngeal
      tumors. The paraffin embedded biopsy samples of the original tumor and different
      passages of the new established cell lines were investigated by PCR with
      consensus primers specific for HPV DNA. The findings indicate that HPV infection
      is associated with some larynx carcinomas. The positive association has been
      enhanced when a method of enrichment of epithelial cells from fresh tumor samples
      was used. All tumor cells enriched smears were positive for HPV DNA not only by
      PCR but also by in situ hybridization (ISH). Investigated by PCR, different
      passages of larynx tumor cell lines maintained expression of HPV DNA. At
      subsequent passages ISH gives constantly no signals suggesting a minimal amount
      of viral harbored sequences. In one cell line propagated more than 60 population
      doublings, the chromosomal frequency distribution shifted from modal number 46 at
      the 5(th) passage to 63 at the 60(th) passage. The mechanisms by which persistent
      HPV infection maintains continuous cell proliferation were discussed.

PMID- 12067451
TI  - Tri-dimensional prostate cell cultures in simulated microgravity and induced
      changes in lipid second messengers and signal transduction.
AB  - The high aspect rotating-wall vessel (HARV) was designed to cultivate cells in an
      environment that simulate microgravity. We studied previously the effects of HARV
      cultivation on DU-145 human prostate carcinoma cells. We determined that HARV
      cultivation produced a less aggressive, slower growing, less proliferative, more
      differentiated and less pliant cell than other cell cultivation methods. The
      result was a 3-dimensional (3D) growth model of prostate cancer which mimics in
      vivo tissue growth. This work examines the signal transduction-second messenger
      pathways existing temporarily in these HARV cells and correlates these features
      with the special properties in growth and 3D spheroid formation. We found an
      initial very active ceramide, a diacylglycerol increase together with increases
      in PI-PLC and PLA(2) a central defect in PLD (no phosphatic acid or
      phosphatidylethanol at any time during 15 days of HARV cultivation). There is a
      cross-talk between ceramide and PI3K pathways with activation of PI3K, after 6
      days of HARV growth concomitant with down-regulation of ceramide. At this time,
      there is also an increase of cAMP (seen by increases in arachidonic acid). Taken
      together these results can explain the 3D organoid-like growth. We therefore
      developed a model for growth in HARV prostate cancer cells which involve temporal
      "switches" between second messengers, activation and cross-talk between
      multiplicity of signaling pathways and a central defect in PLD pathways.
      Essential to the late slow growth, and 3D organotypic formation are the
      apoptotic, anti-survival, anti-proliferation and differentiation pathways in the
      first days of HARV, with growth of "new" different types of prostate cancer cells
      which set-up for later "switch" in ceramide-PI3K to survival and proliferation.

PMID- 12067452
TI  - Localizing genes in Drosophila melanogaster polytene chromosomes by fluorescence
      in situ hybridization.
AB  - This paper describes a method for the identification of single copy genes in
      Drosophila melanogaster polytene chromosomes, using fluorescence in situ
      hybridization (FISH). We demonstrate the detection of white (w), a gene
      previously mapped to 1-1.5 region of the linkage map, and to 3C2 region of the
      cytogenetic map of X chromosome. Squash preparations of polytene chromosomes from
      salivary glands dissected out from third instar larvae of Drosophila melanogaster
      were denatured and subjected to hybridization with a digoxigenin labeled probe,
      corresponding to mini-white gene. The preparations were then washed and incubated
      with anti-digoxigenin-fluorescein antibodies. After removal of the
      nonspecifically bound antibodies, the polytene chromosomes were counterstained
      with propidium iodide. Fluorescence microscopy revealed white locus in the X
      chromosome in a subterminal location, in agreement with the above mentioned maps.
      The protocol is efficient and adaptable for simultaneously multiple signal
      detection.

PMID- 12067453
TI  - Abnormalities of platelet aggregation in chronic myeloproliferative disorders.
AB  - A large variety of platelet dysfunctions has been described in chronic
      myeloproliferative disorders. These abnormalities may be due to deficiency of
      platelet granules, arachidonic acid metabolism defects or platelet membrane
      glycoproteins abnormalities. In this study we intend to detect the incidence of
      platelet function defects in 76 patients with various types of chronic
      myeloproliferative disorders. The platelet activity was studied in vitro by
      measuring platelet aggregation in response to ADP, epinephrine, collagen,
      arachidonic acid and ristocetin. These results were subsequently correlated with
      bleeding time and clinical aspects (bleeding or thrombosis). We found complex
      changes in platelet response with all agonists, in varied proportions. These
      abnormalities include absent, decreased or abnormal platelet aggregation
      response. In a few cases we found a markedly decreased, almost absent platelet
      response to all agonists while in some patients a normal platelet aggregation was
      noted. The correlation between these results and template bleeding time,
      thrombotic or hemorrhagic events and the type of diseases was difficult to
      establish and sometimes conflictual. Despite this fact, we consider that
      investigating platelet aggregation may be useful not only for the assessment of
      the hemostatic balance in chronic myeloproliferative disorders but also for a
      better insight into cell abnormalities occurring in these pathologic conditions.

PMID- 12067454
TI  - TRH synthesis in "mute" thyrotropinomas: cause-effect or coincidence?
AB  - In the pathogenesis of thyrotropin (TSH) immunopositive pituitary adenomas,
      trigger mutagenetic events are well recognized. However, the way towards a
      clinical significant tumor is followed under the pressure of growth factors,
      among which the intrapituitary synthesis of releasing factors could bring a
      significant contribution. In this study, the production of thyrotropin releasing
      hormone (TRH) and beta TSH chain was evaluated at the mRNA level by in situ
      hybridization and end product level by immunohistochemistry, in 18 patients
      submitted to neurosurgery for pituitary macroadenomas. The hormonal sampling
      showed abnormal secretion for FSH in 5 and TSH in 4 patients. Seven cases were
      immunopositive for TSH, and expressed TSH beta mRNA. All but one out of these
      expressed also TRH mRNA. FSH immunoreactivity was documented in 12/ 18, only one
      of these being negative for TRH mRNA. Paracrine TRH could contribute to the
      pathogenesis of these "mute" adenomas.

PMID- 12067455
TI  - Three dimensional configuration of mitochondria in left ventricular myocyte in
      mitochondrial cardiomyopathy: scanning electron microscopy by the osmium-DMSO
      osmium method.

PMID- 12067456
TI  - Detection of human papillomaviruses in lesions of the uterine cervix.

PMID- 12067457
TI  - Drug therapy of primary biliary diseases: classical and modern strategies.

PMID- 12067458
TI  - Stem cell generation and choice of fate: role of cytokines and cellular
      microenvironment.
AB  - Hematopoietic stem cells (HSC) have provided a model for the isolation,
      enrichment and transplantation of stem cells. Gene targeting studies in mice have
      shown that expression of the thrombopoietin receptor (TpoR) is linked to the
      accumulation of HSCs capable to generate long-term blood repopulation when
      injected into irradiated mice. The powerful increase in vivo in HSC numbers by
      retrovirally transduced HOX4B, a homeotic gene, along with the role of the TpoR,
      suggested that stem cell fate, renewal, differentiation and number can be
      controlled. The discovery of the precise region of the mouse embryo where HSCs
      originate and the isolation of supporting stromal cell lines open the possibility
      of identifying the precise signals required for HSC choice of fate. The
      completion of human genome sequencing coupled with advances in gene expression
      profiling using DNA microarrays will enable the identification of key genes
      deciding the fate of stem cells. Downstream from HSCs, multipotent hematopoietic
      progenitor cells appear to co-express a multiplicity of genes characteristic of
      different blood lineages. Genomic approaches will permit the identification of
      the select group of genes consolidated by the commitment of these multipotent
      progenitors towards one or the other of the blood lineages. Studies with neural
      stem cells pointed to the unexpected plastic nature of these cells. Isolation of
      stem cells from multiple tissues may suggest that, providing the appropriate
      environment/ signal, tissues could be regenerated in the laboratory and used for
      transplantation. A spectacular example of influence of the environment on cell
      fate was revealed decades ago by using mouse embryonic stem cells (ES). Injected
      into blastocysts, ES cells contribute to the formation of all adult tissues.
      Injected into adult mice, ES cells become cancer cells. After multiple passages
      as ascites, when injected back into the blastocyst environment, ES- derived
      cancer cells behaved again as ES cells. More recently, the successful cloning of
      mammals and reprogramming of transferred nuclei by factors in the cytoplasm of
      oocytes turned back the clock by showing that differentiated nuclei can be "re
      booted" to generate again the stem cells for different tissues.

PMID- 12067459
TI  - Neurons bearing presenilins: weapons for defense or suicide?
AB  - Apoptotic machinery designed for cell's organized self-destruction involve
      different systems of proteases which cleave vital proteins and disassemble
      nuclear and cytoplasmic structures, committing the cell to death. The most
      studied apoptotic proteolytic system is the caspase family, but calpains and the
      proteasome could play important roles as well. Alzheimer's disease associated
      presenilins showed to be a substrate for such proteolytic systems, being
      processed early in several apoptotic models, and recent data suggest that
      alternative presenilin fragments could regulate cell survival. Mutations in genes
      encoding presenilins proved to sensitize neurons to apoptosis by different
      mechanisms e.g. increased caspase-3 activation, oxyradicals production and
      calcium signaling dysregulation. Here we review the data involving presenilins in
      apoptosis and discuss a possible role of presenilins in the regulation of
      apoptotic biochemical machinery.

PMID- 12067460
TI  - New molecular mediators in tumor angiogenesis.
AB  - Angiogenesis is essential for tumor growth and progression. It has been
      demonstrated that tumor growth beyond a size 1 to 2 mm(3) requires the induction
      of new vessels. Angiogenesis is regulated by several endogenous stimulators and
      inhibitors of endothelial cell migration, proliferation and tube formation. Under
      physiological conditions these mediators of endothelial cell growth are in
      balance and vessel growth is limited. In fact, within the angiogenic balance
      endothelial cell turnover is sufficient to maintain a functional vascular wall
      but does not allow vessel growth. Tumor growth an progression has successfully
      been correlated to the serum concentration of angiogenic mediators. Furthermore,
      the vascular density of tumor tissues could be correlated to the clinical course
      of the disease in several tumor entities. Within the last years several new
      mediators of endothelial cell growth have been isolated e.g. angiopoietin 1,
      angiopoietin 2, midkine, pleiotropin, leptin and maspin. In this review we
      discuss the mechanisms leading to tumor angiogenesis and describe some of the
      newer mediators of endothelial cell stimulation and inhibition.

PMID- 12067461
TI  - Comparative studies of the protein composition of red blood cell membranes from
      eight mammalian species.
AB  - The polypeptide pattern of red blood cell (RBC) membranes from cow, sheep, horse,
      rabbit, guinea pig, rat, mouse, analyzed by polyacrylamide gel electrophoresis,
      was compared to human RBC counterpart. Some qualitative and quantitative
      differences were noted. Among the high molecular weight components the bands 2.1
      2.3 appeared slightly decreased in rabbit and rat and increased in sheep RBC
      membranes. Band 3 appeared to have a higher molecular weight in the cow, guinea
      pig and mouse RBCs, and a lower molecular weight in the sheep RBCs. Band 4.1 from
      the RBC membranes of cow, sheep, rabbit and guinea pig was splitted into two sub
      bands, while band 4.2 overlapped with band 4.1 in horse and guinea pig RBC
      membranes. There are marked differences in the number and position of bands in
      the 4.5 region, while band 4.9 is present in higher amounts in horse, rabbit and
      guinea pig RBC membranes. Band 6 (glyceraldehyde 3-phosphate dehydrogenase) was
      undetectable in horse, rat and mouse RBC membranes and was decreased in sheep,
      rabbit and guinea pig. There are also major differences in the region of band 7
      and below ("post-7"). Band 8 was undetectable in horse, cow and guinea pig, and
      was in higher amounts in rat. A band corresponding to a molecular weight of about
      22 kD in the "post-8" region was present only in guinea pig RBC membranes.

PMID- 12067462
TI  - Beta-cell dysfunctions and insulin resistance in subjects with increased risk for
      type 2 diabetes mellitus.
AB  - The aim of this study was to test if a beta-cell defect is associated to
      deterioration of glucose tolerance early during the natural history of the type 2
      diabetes mellitus. In 41 overweight women, with macrosomic infants in their
      antecedent deliveries, measures of insulin response and insulin sensitivity were
      derived from a short (45 min) iv glucose test. The early (EIR) and the late (LIR)
      phase insulin responses and the insulin sensitivity index (Si) were calculated.
      According the response to 75 g oral glucose test the subjects were divided into
      two groups: Impaired glucose tolerance (IGT; n = 12), and normal glucose
      tolerance (NGT; n = 29). EIR was reduced in IGT group (14.9 +/- 3.6 vs 37.0 +/-
      4.0; p < 0.002). Glucose tolerance during oral glucose tolerance test (OGTT),
      correlated inversely to EIR (r = -0.45; n = 41; p < 0.01). A strong correlation
      of EIR to LIR (r = 0.88; n = 41; p < 0.001) but no correlation between glucose
      tolerance and Si was found.

PMID- 12067463
TI  - Apoptosis in human embryo development: 1. Cerebral cortex.
AB  - We investigated the apoptosis at the beginning of human cerebral cortex
      development, in the 6th week of embryogenesis, Carnegie stages 16 and 17.
      Attention was focused on the dorsal wall of the telencephalon to the ventricular
      zone of proliferation and to the postmitotic zone with beginning of neuronal
      migration. We identified apoptotic cells in tissue sections by propidium iodide
      staining, TUNEL and immunohistochemistry for Fas(APO-1/CD95). We determined the
      distribution and the percentage (reported to the propidium iodide stained nuclei)
      of apoptotic TUNEL-positive and Fas(APO-1/CD95)-positive cells. TUNEL-positive
      apoptotic cells in the proliferative zone were 20% in stage 16 and 60% in stage
      17. TUNEL-positive apoptotic cells in the postmitotic zone were 8% in stage16 and
      30% in stage 17. CD95-positive apoptotic cells in the proliferative zone were 5%
      in stage 16 and 2% in stage 17. There were no CD95-positive cells in the
      postmitotic zone. We evidentiated the presence of the suicide receptor Fas(APO
      1/CD95) only on a small population of apoptotic neuroblasts in the proliferative
      zone. The differences between apoptotic distribution and receptors in early
      corticogenesis suggest that different apoptotic pathways drive the selection of
      neuronal populations.

PMID- 12067464
TI  - Merosin-deficient congenital muscular dystrophy: neuropathology case reports.
AB  - The aims of our study were: to present cases of congenital muscular dystrophy
      (CMD) with deficiency in merosin and the importance of immunohistochemistry in
      the diagnosis of merosin-deficient CMD. In four years (1997-2000), we found three
      patients with merosin-deficient CMD, one of them having an unusual clinical and
      pathological manifestation of the disease. Muscle biopsies of gastrocnemius or
      quadriceps muscles were investigated. In addition with the conventional HE
      staining, indirect immunohistochemistry for merosin, dystrophin, utrophin and for
      the proteins of the dystrophin associated complex (alpha-, beta-, gamma-
      sarcoglycans; beta-dystroglycan) was performed on cryosections. The findings
      suggest that there is no correlation between the clinical and histological
      picture of the disease and the expression of merosin in skeletal muscles. The
      degree of muscle involvment (assessed by histology) is parallel with the clinical
      neuromotor deficiency, but not with expression of merosin, which can be absent
      even in mild cases. The clinical investigations as well as current morphological
      techniques, only together with immunohistochemistry can differentiate between
      merosin - deficient CMD and other muscular dystrophy forms.

PMID- 12067465
TI  - Genetic analysis of factor V Leiden in a family with history of thrombosis and
      venous leg ulcers.
AB  - Inherited resistance to activated protein C has been recognized as a major risk
      factor for thrombosis. The factor V Leiden mutation, which is detectable by
      molecular DNA techniques, is responsible for 95% of cases of activated protein C
      resistance. In our study one patient with venous leg ulcers from a family with a
      history of thrombosis showed factor V Leiden mutation. Genotypic analysis
      demonstrated that the patient was homozygous for factor V Leiden. All family
      members of the index subject showed the same abnormalities. Two were homozygous
      and 3 were heterozygous for factor V Leiden mutation. The polymerase chain
      reaction was used to amplify exon 10 of the factor V gene, followed by enzymatic
      digestion with MnlI for mutation detection. Patients with a family history of
      thrombosis and factor V Leiden have an increased risk of venous leg ulcers.
      Screening for factor V Leiden may be indicated in patients with venous leg ulcers
      and their family members.

PMID- 12067466
TI  - Alzheimer's disease: plaques and tangles.

PMID- 12067467
TI  - Follicular dendritic cells - a reservoir for immunodeficiency virus.

PMID- 12067468
TI  - Long-term Helicobacter pylori colonization produces G cell hyperplasia and
      carcinoid tumor in Mongolian gerbils.

PMID- 12067469
TI  - Gap junction remodeling and cardiac arrhythmogenesis: cause or coincidence?
AB  - Gap junctions, clusters of transmembrane channels that link adjoining cells,
      mediate myocyte-to-myocyte electrical coupling and communication. The component
      proteins of gap junction channels are termed connexins and, in in vitro
      expression systems, gap-junctional channels composed of different connexin types
      exhibit different biophysical properties. In common with other tissues, the heart
      expresses multiple connexin isoforms. Spatially defined patterns of expression of
      three connexin isoforms - connexin43, connexin40 and connexin45 - form the cell
      to-cell conduction pathways responsible for the orderly spread of current flow
      that governs the normal cardiac rhythm. Remodeling of gap junction organization
      and connexin expression is a common feature of human heart disease conditions in
      which there is an arrhythmic tendency. This remodeling may take the form of
      disturbances in the distribution of gap junctions and/or quantitative alterations
      in connexin expression, notably reduced ventricular connexin43 levels. The idea
      that such changes may contribute to the development of a pro-arrhythmic substrate
      in the diseased heart has gained ground over the last decade. Recent studies
      using transgenic mice models have raised new opportunities to explore the
      significance of gap junction remodeling in the diseased heart.

PMID- 12067470
TI  - Prion diseases: contribution of high-resolution immunomorphology.
AB  - The transmisible spongiform encephalopathies or prion diseases are fatal
      neurological diseases that occur in animals and humans. They are characterized by
      the accumulation in the cerebral tissue of the abnormal form of prion protein
      (PrPsc) produced by a post-translational event involving conformational change of
      its normal cellular counterpart (PrPc). In this short review, we present some
      results on the biology of prion proteins which have benefited from morphological
      approaches combining the electron microscopy techniques and the immunodetection
      methods. We discuss data concerning in particular the physiological function of
      the normal cellular prion prion (PrPc) which have allowed to open up new vistas
      on prion diseases, the biogenesis of amyloid plaque and the cellular site
      involved in the prion protein conversion process.

PMID- 12067471
TI  - Statins: mechanism of action and effects.
AB  - The beneficial effects of statins are the result of their capacity to reduce
      cholesterol biosyntesis, mainly in the liver, where they are selectively
      distributed, as well as to the modulation of lipid metabolism, derived from their
      effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic
      effects, that positively correlate with the percent decrease in LDL cholesterol.
      In addition, they can exert antiatherosclerotic effects independently of their
      hypolipidemic action. Because the mevalonate metabolism generates a series of
      isoprenoids vital for different cellular functions, from cholesterol synthesis to
      the control of cell growth and differentiation, HMG-CoA reductase inhibition has
      beneficial pleiotropic effects. Consequently, statins reduce significantly the
      incidence of coronary events, both in primary and secondary prevention, being the
      most efficient hypolipidemic compounds that have reduced the rate of mortality in
      coronary patients. Independent of their hypolipidemic properties, statins
      interfere with events involved in bone formation and impede tumor cell growth.

PMID- 12067472
TI  - Maintenance of size and function of influenza virus hemagglutinin specific
      transgenic T-cell clone during life.
AB  - Immunization induces less protective immunity against infectious diseases in old
      compared to young subjects. We have studied the effect of age on the in vitro and
      in vivo function of murine transgenic T cells expressing a receptor for influenza
      hemagglutinin 110-120 peptide. During aging the transgenic T cells undergo the
      age-associated shift from naive to memory phenotype but maintain, despite thymic
      involution, their number as well as their cytokine production and proliferative
      responses induced by the hemagglutinin 110-120 peptide in vitro. The maintenance
      of the size and functions of transgenic T cells during the aging may be related
      to low expression of CTLA-4 molecules known to exhibit a negative regulatory
      effect subsequent to interaction with costimulatory molecules as well as of
      stimulation of T cells by unknown cross reactive endogenous factors but not by
      nominal antigen since innate immunity prevents natural infection with influenza
      virus of murine species. This suggests that the impaired immunity induced by
      immunization in old subjects reflects defects in the development and maintenance
      of T cell memory and not in the expression of effector activity.

PMID- 12067473
TI  - G20210A prothrombin gene mutation identified in patients with venous leg ulcers.
AB  - The G20210A mutation variant of prothrombin gene is the second most frequent
      mutation identified in patients with deep venous thrombosis, after factor V
      Leiden. The risk for developing deep venous thrombosis is high in patients
      identified as heterozygous for G20210A mutation. In order to identify this
      polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'-
      untranslated region of the prothrombin gene was amplified using amplification by
      polymerase chain reaction and enzymatic digestion by HindIII (restriction
      endonuclease enzyme). The products of amplification and enzymatic's digestion
      were analized using agarose gel electrophoresis. We investigated 20 patients with
      venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of
      the patients in the control group had G20210A mutation. Our study confirms the
      presence of G20210A mutation in the Romanian population. Our study also shows the
      link between venous leg ulcers and this polymorphism in the prothrombin gene.

PMID- 12067474
TI  - Basic studies on gene therapy of human malignant melanoma by use of the human
      interferon beta gene entrapped in cationic multilamellar liposomes. 1. Morphology
      and growth rate of six melanoma cell lines used in transfection experiments with
      the human interferon beta gene.
AB  - Six cell lines of human malignant melanoma: A375, A375.2, G361, HMV-1, MM8.1 and
      WM115 were seeded at densities of 1x10(4) cells/ml, 2 x 10(4) cells/ml or 3 x
      10(4) cells/ml of RPMI medium supplemented with 10% fetal calf serum and
      antibiotics in a humidified atmosphere of 5% CO2 at 37 degrees C. A375 cells were
      also grown in Dulbecco's minimum Eagle's medium (DMEM medium). The morphology was
      studied by phase contrast light microscopy. At 4 days after seeding the colonies
      of A375 cells and HMV-1 cells were oval-shaped, the cells were polyhedrical and
      were making contact with each other regularly. The remaining cells were
      scattered, more elongated, and made contact randomly. G361 cells and MM8.1 cells
      tended to form superposed layers before 100% confluency was achieved. There were
      great differences in the growth rate and doubling time of melanoma cells. The
      doubling time in day 1 was short (around 6-12 h) in the case of A375, G361 and
      HMV-1 cells, longer (around 18 h) in the case of MM8.1 cells and very long
      (ranging between 26 and 89 h) for A375.2 and WM115 cells. There were also
      differences in the doubling time of cells as a function of the cell density at
      seeding. On the other hand, except for MM8.1 cells, there were differences
      between the doubling time in day 2 compared to day 1.

PMID- 12067475
TI  - Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine
      treatment.
AB  - It was investigated the in vivo effect of glutethimide on the intracellular
      neuroadaptation characteristic for m-opioid receptor tolerance induced by chronic
      codeine treatment and reflected by increased levels of adenylyl cyclase (AC) and
      cAMP-dependent protein kinase (PKA). AC activity was appreciated by cyclic-AMP
      (cAMP) formation, the levels of adenine and guanine nucleotides in brain extracts
      being assayed using a high performance liquid chromatographic method. The
      concomitant chronic administration of codeine and glutethimide resulted in a
      pronounced and long-lasting energetic depletion of the neurons, consistent with
      the high risk of overdose, and increase of cAMP's stable metabolite, 5'-AMP. This
      increase is persistent even after withdrawal and suggests an interference with
      the adenylyl cyclase system involved in the development of tolerance of opioid
      receptor and in relapse and provides a possible explanation of addiction and fast
      increase of doses observed in humans abusing this combination.

PMID- 12067477
TI  - Akt and PTEN: new diagnostic markers of non-small cell lung cancer?
AB  - We are particularly interested in testing the principles of cell proliferation
      and apoptosis in the microenvironment of human lung cancers with respect to the
      cell survival protein Akt 1 and PTEN 2. Akt is a cytosolic protein which promotes
      cell survival by phosphorylative inactivation of targets in apoptotic pathways.
      Akt has been found to play a role in the survival of experimental cancer cell
      lines in breast, prostate, ovary, lung and brain tissue. PTEN is a tumor
      suppressor gene whose protein product is expressed in inverse proportion to
      phosphorylated Akt in endometrial and breast cancer cell lines. No studies of the
      diagnostic significance of Akt and PTEN in human lung cancers have been reported.

PMID- 12067476
TI  - Apoptosis in human embryo development: 3. Fas-induced apoptosis in brain primary
      cultures.
AB  - Fas (APO-1/CD95) is an important apoptotic mediator for both immune and nervous
      systems. In the present study, we have investigated the expression and function
      of Fas in human embryonic/fetal brain primary cultures from 12 human embryos and
      fetuses with gestational ages between 5 to 22 weeks. Anti-Fas fluorescent
      antibody was used for labeling of Fas positive cells and for quantitation of Fas
      expression in brain cultures. To demonstrate that Fas receptor is functional in
      human embryonic/fetal brain cells, anti-Human-Fas monoclonal antibody (0.5
      microg/ml) was used to induce apoptosis in brain primary cultures. Apoptosis was
      investigated by flow-cytometry and fluorescent microscopy using TUNEL and annexin
      V labeling. Fas was found to be expressed in the embryonic/fetal human primary
      brain cultures, on neuronal and glial cells or their precursors, varying with
      gestational ages. Cross-linking of Fas induced apoptosis in brain cultures
      indicating that Fas receptor functions as a death receptor. We also showed that
      cell death triggered through Fas receptor was caspase dependent, hence it was
      blocked by a selective caspase-8 inhibitor (IETD-fmk). These results suggest that
      Fas is involved in neuronal apoptosis in the developing human brain.

PMID- 12067478
TI  - Hyperplasia of gonadotropin-secreting cells in FSH receptor knock-out male mice.

PMID- 12067479
TI  - Disseminated infection of the digestive tract caused by cytomegalic virus in a
      patient with Hodgkin's disease.

PMID- 12067480
TI  - Phagocytosis of apoptotic cells by microglia in vitro.

PMID- 12067481
TI  - Classification of thymic epithelial neoplasms: a controversial issue coming to an
      end?
AB  - The classification of thymic epithelial neoplasms has been one of the most
      controversial issues in tumor pathology. There are two opposing schools of
      pathologists holding different views regarding the classification of thymic
      epithelial neoplasms. One school of pathologists believe that histological
      classification of thymomas is not possible or useful. Another school of
      pathologists believe that thymomas can be histologically subclassified despite
      their complex histomorphology and that these histological subtypes correlate with
      their aggressiveness and clinical behavior. A compromised histological
      classification has been established by World Health Organization (WHO) to
      designate thymic epithelial neoplasms with letters and numbers. This
      classification should be adopted internationally to facilitate the communication
      among concerned pathologists and oncologists. A simple histological
      classification of thymomas based on cytomorphology and supported by cytokeratin
      expressions is proposed and compared to the WHO and Muller-Hermelink's
      histogenetic classifications.

PMID- 12067482
TI  - Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding
      proteins.
AB  - Several mechanisms have been identified by which protein synthesis may be
      regulated during the response of mammalian cells to physiological stresses and
      conditions that induce apoptotic cell death (reviewed in Clemens et al., Cell
      Death and Differentiation 7, 603-615, 2000). Recent developments allow us to up
      date this analysis and in this article I concentrate on one particular aspect of
      this regulation that has not previously been reviewed in depth in relation to
      apoptosis, viz. the control of the initiation of protein synthesis by eukaryotic
      initiation factor eIF4E and the eIF4E binding proteins (4E-BPs). Changes in the
      state of phosphorylation of the 4E-BPs and in the extent of their association
      with eIF4E occur at an early stage in the response of cells to apoptotic
      inducers. The review discusses the mechanisms by which these events are regulated
      and the significance of the changes for the control of protein synthesis, cell
      proliferation and cell survival.

PMID- 12067483
TI  - New concepts in radiation-induced apoptosis: 'premitotic apoptosis' and
      'postmitotic apoptosis'.
AB  - Formerly, the mechanisms responsible for the killing of cells by ionizing
      radiation were regarded as being divided into two distinct forms, interphase
      death and reproductive death. Since they were defined based on the classical
      radiobiological concepts using a clonogenic cell survival assay, biochemical and
      molecular biological mechanisms involved in the induction of radiation-induced
      cell death were not fully understood in relation to the modes of cell death.
      Recent multidisciplinary approaches to cell death mechanism have revealed that
      radiation-induced cell death is divided into several distinct pathways by the
      time course and cell-cycle position, and that apoptotic cell death plays a key
      role in almost every mode of cell death. This review discusses the mechanisms of
      radiation-induced apoptosis in relation to cell-cycle progression and highlights
      a new concept of the mode of cell death: 'premitotic apoptosis' and 'postmitotic
      apoptosis'. The former is a rapid apoptotic cell death associated with a prompt
      activation of caspase-3, a key enzyme of intracellular signaling of apoptosis. A
      rapid execution of cell killing in premitotic apoptosis is presumably due to the
      prompt activation of a set of pre-existed molecules following DNA damages. In
      contrast, the latter is a delayed apoptotic cell death after cell division, and
      unlike premitotic apoptosis, it neither requires a rapid activation of caspase-3
      nor is inhibited by a specific inhibitor, Ac-DEVD-CHO. A downregulation of anti
      apoptotic genes such as MAPK and Bcl-2 may play a key role in this mode of cell
      death. Characterization of these two types of apoptotic cell death regarding the
      cell cycle regulation and intracellular signaling will greatly help to understand
      the mechanisms of radiation-induced apoptosis.

PMID- 12067484
TI  - Apolipoprotein E: a major piece in the Alzheimer's disease puzzle.
AB  - Alzheimer's disease (AD) is a complex neurodegenerative disorder with multiple
      etiologies. The presence of the E4 isoform of apolipoprotein E (apoE) has been
      shown to increase the risk and to decrease the age of onset for AD and is the
      major susceptibility factor known for the disease. ApoE4 has been shown to
      intensify all the biochemical disturbances characteristic of AD, including beta
      amyloid (Abeta) deposition, tangle formation, neuronal cell death, oxidative
      stress, synaptic plasticity and dysfunctions of lipid homeostasis and cholinergic
      signalling. In contrast, other apoE isoforms are protective. Here we review and
      discuss these major hypotheses of the apoE4-AD association.

PMID- 12067485
TI  - Quality control of gene expression in the nucleus.
AB  - Proteins are responsible for most cellular and extra-cellular functions. If
      altered, proteins can loose their normal activity and/or gain new properties.
      Either way the consequences may be deleterious for the cell and lead to disease
      at the organism level. Not surprisingly, eukaryotes have evolved mechanisms to
      recognize abnormal messenger RNAs and prevent them from producing faulty
      proteins. Protein-encoding genes are transcribed in the nucleus by RNA polymerase
      II as precursor RNAs that undergo extensive processing before being translocated
      to the cytoplasm for translation by the ribosomes. This spatial and temporal
      separation between RNA and protein synthesis offers an immense opportunity for
      control and regulation. Here we review recent studies that are beginning to
      unravel how the coupling between transcription, processing and transport of mRNAs
      contributes to control the quality of gene expression in the nucleus.

PMID- 12067486
TI  - Renal cortical remodelling by NO-synthesis blockers in rats is prevented by
      angiotensin-converting enzyme inhibitor and calcium channel blocker.
AB  - The cortical remodelling was studied when chronically nitric oxide synthesis
      (NOs) blockade (L-NAME-induced) hypertensive rats are simultaneously treated, or
      not, with angiotensin-converting enzyme inhibitor or calcium channel blocker.
      Four groups of eight rats each were studied as follows: Control (C), L-NAME (L),
      L-NAME+Enalapril (L+E) and L-NAME+Verapamil (L+V). The systolic blood pressure
      (SBP) was weekly recorded. The cortex of the left kidneys was analysed according
      to the vertical section design. The volume-weighted mean glomerular volume (VWGV)
      was made through the "point-sampled intercepts" method. Enalapril and verapamil
      were efficient in reducing the SBP in rats submitted to NOs blockade. Glomeruli
      had considerable alterations in L group rats (glomerular hypertrophy or
      sclerosis) and tubular atrophy. The VWGV was 100% greater in L group rats than in
      the C group rats, while it was 30% smaller in L+E and L+V groups than in L group.
      The tubular volume was 30-50% greater, while the tubular length was 20-30%
      smaller in the L group than in the other groups. The renal cortical region showed
      glomerular sclerosis/hypertrophy and tubular remodelling in rats with NOs
      blockade that was efficiently prevented with the simultaneous treatment with
      enalapril or verapamil.

PMID- 12067487
TI  - The total peroxyl radical trapping potential in serum - an assay to define the
      stage of atherosclerosis.
AB  - Lipid peroxides were identified among the factors that contribute to the
      atherosclerotic plaque formation in the arterial wall. We hypothesised that a
      correlation may exist between the content of antioxidant constituents in the
      serum and the gravity of atherosclerosis. To this purpose, we have determined the
      serum total peroxyl radical- trapping potential (TRAP), which is the combined
      capacity of all antioxidants to neutralize free radicals in serum and followed
      its variation in hyperlipemic animals in correlation with the stage of
      atherosclerosis. In addition, we compared TRAP values in the sera of coronary
      heart disease (CHD) patients, with or without type II diabetes mellitus. Results
      showed that after 18 weeks of hyperlipemic diet, the mean TRAP values measured in
      sera isolated from hyperlipemic hamsters exhibited an about 44% decrease, in good
      agreement with the increase of serum cholesterol and triglycerides. In the 3
      groups of CHD patients, TRAP values decreased with about 10% in sera of stable
      angina patients, 20% in unstable patients, as compared with normal subjects. The
      lowest TRAP values were detected in the sera of patients with acute myocardial
      infarction. The results obtained for different experimental animals and for CHD
      patients sera indicate that the TRAP method, as adapted in our laboratory, is a
      reliable and reproducible assay, fit to be used in clinical studies as an ex vivo
      measurable parameter that correlates with the stage of the atherosclerosis.

PMID- 12067488
TI  - Cell viability of retinal photoreceptor evaluated by polar distribution of Ca(2+)
      and electrical charge.
AB  - The polar organisation is characteristic to the living cell and disappears with
      the cell functional decay. Here we report experimental evidence that frog retinal
      photoreceptor rod cell shows a polar distribution of the electrical charge and of
      free cytosolic Ca(2+) along its length. Retinal rod cells were loaded with
      Calcium sensitive dye (Green1) and examined under fluorescence microscopy coupled
      with an image analysis system. In addition, suspension of rod cells was placed in
      direct current electric field for electrical polarity assessment. Both polar
      Ca(2+) and electrical charge distribution can be objectively measured and
      quantified providing thus a fine test for cell viability. Such a test is required
      in checking the functional integrity of photoreceptors used in retinal
      transplant.

PMID- 12067489
TI  - Prevalence of virulence genes in Escherichia coli strains isolated from Romanian
      adult urinary tract infection cases.
AB  - A total of 78 E. coli strains isolated from adults with different types of
      urinary tract infections were screened by polymerase chain reaction for
      prevalence of genetic regions coding for virulence factors. The targeted genetic
      determinants were those coding for type 1 fimbriae (fimH), pili associated with
      pyelonephritis (pap), S and F1C fimbriae (sfa and foc), afimbrial adhesins (afa),
      hemolysin (hly), cytotoxic necrotizing factor (cnf), aerobactin (aer). Among the
      studied strains, the prevalence of genes coding for fimbrial adhesive systems was
      86%, 36%, and 23% for fimH, pap, and sfa/foc,respectively. The operons coding for
      Afa afimbrial adhesins were identified in 14% of strains. The hly and cnf genes
      coding for toxins were amplified in 23% and 13% of strains, respectively. A
      prevalence of 54% was found for the aer gene. The various combinations of
      detected genes were designated as virulence patterns. The strains isolated from
      the hospitalized patients displayed a greater number of virulence genes and a
      diversity of gene associations compared to the strains isolated from the
      ambulatory subjects. A rapid assessment of the bacterial pathogenicity
      characteristics may contribute to a better medical approach of the patients with
      urinary tract infections.

PMID- 12067490
TI  - Immunohistochemical features of paragangliomas.
AB  - Immunohistochemistry is part of the routine diagnosis of the neuroendocrine
      tumors. In our study, we included 52 paragangliomas with various localizations by
      routine histology and immunohistochemistry. In order to increase the diagnostic
      specificity, a complex immunohistochemistry panel has been performed consisting
      of Bcl-2, Ki-67, Bax and Pituitary Adenylate Cyclase-Activating Peptide (PACAP),
      somatostatin, VIP and Calcitonin Gene Related Peptide (CGRP). After heat induced
      antigen retrieval, the immunostaining was performed by StreptABC using DAB as a
      chromogen. We were the first to demonstrate the presence of Bax and PACAP in
      paragangliomas. Some of the used markers are of prognostic value. The
      relationship between Bcl-2 and Bax is decisive in generating the final response
      to the input apoptotic signals. The Ki-67 antigen staining has gained wide
      acceptance in prognostic evaluation of other tumor types. We noted a small number
      of Ki-67 positive cases, which signifies a low mitotic activity of these tumors
      and a relatively high number of Bax positivities (32.9%) and the much lower
      number of Bcl-2 positivities (11.39%), and could explain the benign behaviour of
      paragangliomas.

PMID- 12067491
TI  - Intraneuronal Lewy body inclusions in Parkinson and diffuse Lewy body disease.

PMID- 12067492
TI  - Cellular components of the air-blood barrier.

PMID- 12067493
TI  - In vitro differentiation of human embryonic neural stem cells.

PMID- 12067494
TI  - Altered mucin expression in the gastrointestinal tract: a review.
AB  - Early studies of changes in mucin expression in disorders of the gastrointestinal
      tract focused on alterations in the carbohydrate chain. This review briefly
      considers the various mechanisms by which such alterations may come about: (a)
      normal variation, (b) sialic acid alterations, (c) defective assembly of
      carbohydrate side-chains, (d) changed expression of core proteins and (e)
      epithelial metaplasia. The availability of monoclonal antibodies to mucin core
      proteins adds a new dimension to mucin histochemistry. It is now possible to
      offer explanations for traditional mucin histochemical findings on the basis of
      lineage-specific patterns of mucin core protein expression. Changes in core
      protein expression are described in inflammatory, metaplastic and neoplastic
      disorders of the gastrointestinal tract. The possibility that mucin change could
      be important in the aetiology of some diseases such as ulcerative colitis and H.
      pylori gastritis is considered. It is more probable, however, that changes in
      mucin expression are secondary to reprogramming of cellular differentiation and
      altered cell turnover. As such they may serve as markers to explain pathogenesis
      and provide novel diagnostic and prognostic information.

PMID- 12067495
TI  - Crossovers between functional and proliferative signaling: key to understanding
      the pathophysiology and management of heart failure.

PMID- 12067496
TI  - Fibroblast growth factors in myocardial ischemia / reperfusion injury and
      ischemic preconditioning.
AB  - Angiogenic growth factors such as fibroblast growth factors (FGFs) are currently
      in clinical trials for accelerating blood vessel formation in myocardial and limb
      ischemic conditions. However, recent experimental evidence suggests that FGFs can
      also participate as endogenous cardioprotective agents. In this report, the
      current knowledge for FGFs implication in myocardial ischemic tolerance will be
      summarized. Pharmacologic preconditioning with drugs as FGFs that mimic the
      beneficial effects of ischemic preconditioning could lead to novel therapeutic
      approaches for the treatment of ischemic disorders including myocardial
      infarction and stroke.

PMID- 12067497
TI  - Cardiac apoptosis: from organ failure to allograft rejection.
AB  - Cardiac myocyte apoptosis has been extensively studied in the last few years.
      Increased interest in the field stems from the hope that pharmacological
      manipulation of apoptosis may become a valuable tool for preventing excessive
      cell death observed in different pathological conditions. This paper is not
      intended as a comprehensive overview of current research about life and death in
      the cardiovascular system, but rather as a concise update on new developments in
      areas that were highlighted in a recent series of excellent reviews. A short
      inventory of unsolved issues concerning the significance of cardiac myocyte loss
      through apoptosis in both physiological and pathological circumstances is
      addressed.

PMID- 12067498
TI  - The hyperlipemic hamster - a model for testing the anti-atherogenic effect of
      amlodipine.
AB  - Male Golden Syrian hamsters were subjected to a hyperlipemic diet. At intervals
      ranging from 2 to 14 weeks, the animals were examined for changes in serum
      constituents and structural modifications of lesion-prone areas: the cardiac
      valves, coronary arteries and aortic arch. Serum was characterized by a gradual
      increase in cholesterol, triglycerides and a decrease in total peroxyl-radical
      trapping potential. The sequence of modifications of the endothelial cells,
      smooth muscle cells, and migrating plasma monocytes as well as of the
      extracellular matrix were established. Amlodipine treatment of hyperlipemic
      hamster was assessed. Amlodipine exhibited an athero-protective effect, acting as
      antioxidant, reducing the LDL uptake by the vessel wall and consequently,
      limiting the size and extent of lesioned areas. The hyperlipemic hamster is a
      reliable model to unravel the cellular alterations leading to atheroma formation,
      and for testing the effect of drugs in this process.

PMID- 12067499
TI  - Oxidative damage following cerebral ischemia depends on reperfusion - a
      biochemical study in rat.
AB  - The extent of brain injury during reperfusion appears to depend on the
      experimental pattern of ischemia/reperfusion. The goals of this study were:
      first, to identify the rate of free radicals generation and the antioxidant
      activity during ischemia and reperfusion by means of biochemical measurement of
      lipid peroxidation (LPO) and both enzymatic (superoxide dismutase - SOD, catalase
      - CAT, glutathione peroxidase - GPx) and non-enzymatic antioxidants activity
      (glutathione - GSH); and second, to try to find out how the pattern of
      reperfusion may influence the balance between free radical production and
      clearance. Wistar male rats were subject of four-vessel occlusion model
      (Pulsinelly & Brierley) cerebral blood flow being controlled by means of two
      atraumatic arterial microclamps placed on carotid arteries. The level of free
      radicals and the antioxidant activity were measured in ischemic rat brain tissue
      homogenate using spectrophotometrical techniques. All groups subjected to
      ischemia shown an increase of LPO and a reduction of the activity of enzymatic
      antioxidative systems (CAT, GPx, SOD) and non-enzymatic systems (GSH). For both
      groups subjected to ischemia and reperfusion, results shown an important increase
      of LPO but less significant than the levels found in the group with ischemia
      only. Statistically relevant differences (p<0.01) between continuous reperfusion
      and fragmented reperfusion were observed concerning the LPO, CAT, SOD and GSH
      levels, oxidative aggression during fragmented reperfusion being more important.

PMID- 12067500
TI  - Can a mixed damage interfere with DNA-protein cross-links repair?
AB  - Some photochemical and photobiological properties of 4,5',8-trimethylpsoralen
      (TMP) have been studied in comparison with 1,4,6,8-tetramethyl-2H-furo[2,3
      h]quinolin-2 one (FQ) and 8-methoxypsoralen (8-MOP). TMP and FQ can photobind to
      mammalian cell DNA in vivo, by UVA irradiation, forming DNA-protein cross-links
      (DPC), but only TMP shows a strong capacity of inducing interstrand cross-links
      (ISC). The mechanism of DPC formation was studied using the double irradiation
      method in Chinese hamster ovary (CHO) cells, and DPC were detected by alkaline
      elution. Both TMP and FQ induce covalent diadducts linking together DNA and
      proteins. Studying the formation of double strand breaks (DSB) in CHO cells we
      observed that TMP induced a low amount of DSB, similar to 8-MOP. TMP and 8-MOP
      induced chromosomal aberrations in CHO cells to the same extent, while FQ
      appeared to be more active. Our data suggest that the ISC induced by TMP could
      trap enzymes involved in DPC repair.

PMID- 12067501
TI  - Effects of synovial fluid on the respiratory burst of granulocytes in rheumatoid
      arthritis.
AB  - Neutrophil infiltration in the synovia is an important feature of the local
      inflammatory process associated with rheumatoid arthritis. The present study is
      focused on the effects exerted in vitro by the synovial fluid versus serum on the
      respiratory burst of granulocytes isolated either from blood or synovial fluid of
      rheumatoid arthritis patients. The respiratory burst was evaluated as superoxide
      anion release, by lucigenin-amplified chemiluminescence. Our data show that the
      respiratory burst of granulocytes isolated from rheumatoid arthritis patients
      might trigger a significant oxidative stress both in periphery and the inflamed
      joint. These cells show no pathological pattern when activated in vitro by the
      chemotactic peptide fMLP, heterologous synovial fluid or serum. Acellular
      synovial fluid amplifies the superoxide anion release induced by fMLP more than
      the corresponding serum, indicating that a bacterial infection in the joint might
      enhance the oxidative damage in the inflamed synovium.

PMID- 12067503
TI  - Morphological changes associated with reoxygenation in adult cardiac myocytes.

PMID- 12067502
TI  - A chemical method to isolate hypothalamic nonapeptides by coupling cyst(e)in with
      bimane.
AB  - Vasopressin, oxytocin as well as other active nonapeptides (vasotocin, etc) are
      difficult to isolate from tissues. Traditionally they were identified using
      cumbersome biological assays or immunoassays, commercially unavailable, and with
      some cross reactivity. Based on the fact that all these peptides have two
      Cysteines in their molecules we developed a simple, sensitive and specific method
      to detect them by HPLC after pre-column fluorescent derivatization with
      monobromobimane (mBBr). The peptides were separated on a Vydac C18 column after
      reduction with Tris (2-carboxyethyl) phosphine (TCEP) and derivatization with
      mBBr for 5 minutes in dark. Using this method we were able to detect specific
      peaks for arginine-, lysine-vasopressin, and vasotocin at levels as low as 10
      pmol. The method can be used to detect other active peptides with cyst(e)ins in
      their molecule, as well.

PMID- 12067504
TI  - Ultrastructural lesions in a case of nephrotic syndrome (minimal change disease).

PMID- 12067505
TI  - Changing structures of university medicine in Germany: new medical teaching and
      broader research scene.

PMID- 12067507
TI  - "Slip and fall" theory--extreme order statistics.
AB  - Classical "slip and fall" analysis was reformulated in this paper to account for
      the stochastic nature of friction. As it turned out, the new theory, arising from
      this analysis, was a precise statement of the distribution function for the
      smallest value among n independent observations. This made it possible to invoke
      an important result from the asymptotic theory of extreme order statistics that
      reduced the theory to a simple and elegant relationship among the probability of
      slipping, the critical friction criterion, the distance traveled by the walker,
      and the average, spread and asymmetry of the distribution of friction
      coefficients. The new theory reveals that short walks lead to fewer falls; low
      friction floors are sometimes better than high friction ones.

PMID- 12067508
TI  - A simulation method of the reduction of nitrogen oxides over a silver aluminate
      catalyst in static tests of combustion engines.
AB  - The paper presents a proposition of simulation studies of nitrogen oxide
      catalytic reduction. The method enables estimating the influence of catalytic
      reactors on ecological properties of engines in static bench tests (e.g., ECE
      R49, United Nations Economic Commission for Europe [UN/ECE], 2000; Standard No.
      ISO 8178-4:1996, International Organization for Standardization [ISO], 1996;
      Merkisz (1998). An algorithm of simulation studies is shown. A model catalytic
      reactor for selective catalytic reduction is described. Silver aluminate
      deposited on steel substrate covered with aluminium phosphate is used as a
      catalyst. Propene is used as a reductant. The results of reactor studies in a
      chemical lab are presented. A simulation of the influence of catalytic reactor
      properties on ecological properties of an engine was done. Unitary emission
      conversion coefficients of nitrogen oxide in a static test ECE R49 were
      determined.

PMID- 12067506
TI  - Apoptosis in human embryo development: 2. Cerebellum.
AB  - We analysed the spatial and temporal distribution of apoptosis in human
      cerebellum development, during embryonic and fetal periods. Cerebella excised
      from two human embryos (8 weeks old) and eight fetuses (12-22 weeks old), were
      paraffin embedded and serially sectioned. Apoptotic cells were identified by
      propidium iodide staining, and TUNEL. In addition, immunohistochemistry for
      suicide receptor Fas(APO-1/CD95) was performed. We determined the distribution
      and percentage of apoptotic cells as well as Fas(APO-1/CD95)-positive cells in
      different regions and stages of development. Apoptotic cells were seen in both
      proliferative zones and postmitotic regions along the migratory pathways as well
      as in the developing cerebellar cortex in all examined stages. The Fas(APO
      1/CD95) immunoreactivity was present in all examined stages in a small population
      of apoptotic cells: either neuroblasts or differentiated cells in postmitotic
      zones. These findings suggest that apoptosis drives the selection of the cells
      which are committed to differentiate during the early stages of cerebellar
      development. The differences between apoptotic cells distribution and Fas
      receptor expression suggest that cell selection is driven by different apoptotic
      pathways.

PMID- 12067509
TI  - Proposal for an indexical method of evaluating risk of hand tool operators'
      exposure to mechanical vibrations.
AB  - The article presents proposals for an indexical evaluation of exposure of hand
      tool operators to vibrations. The presented indices have been developed on the
      basis of the results of laboratory tests. The examinations studied the effect of
      pressure force and grip force exerted by an operator on a hand tool as well as
      the amplitudes and frequencies of an exciting signal on vibrations transmitted in
      the hand-tool handle system.

PMID- 12067510
TI  - Work as a cultural and personal value: attitudes towards work in Polish society.
AB  - The meaning of work for Poles is analyzed here from 2 perspectives: macrosocial
      and individual. From the macrosocial perspective work attitudes are explained by
      3 factors: traditional Polish Catholicism, cultural patterns (influence of noble
      class tradition), and experience of "real socialism." From an individual
      perspective some psychological and demographic predictors of an autonomous
      (intrinsic) work attitude are empirically tested. The autonomous attitude towards
      work is understood here as treating work as an important autonomous value versus
      only an instrumental means for earning money. The data was collected by means of
      standardized interviews run on a representative random sample of adult working
      Poles, N = 1340.

PMID- 12067511
TI  - New equipment to lighten the work load of construction workers.
AB  - The objective of this study was to determine whether the 4 pieces of equipment
      for cutting moulding, cutting reinforcement rods, carrying carpet rolls, and
      fitting drain pipes can lighten the work load of construction work. The results
      indicate that the effect of using the new ergonomically designed equipment was
      positive. The cutter for reinforcement rods proved to be useful, bent back
      postures decreased by 11%. The carrying of carpet rolls became less loading on
      the lower and upper extremities. According to the men the work load was lower in
      fitting drain pipes, especially on the lower extremities and in the neck and
      shoulder region. The conclusion was reached that work load can be decreased with
      well-planned equipment, but more attention should be given to personal work
      methods and habits.

PMID- 12067512
TI  - Ergonomic diagnosis of the driver's workplace in an electric locomotive.
AB  - This paper deals with research aimed at developing a method for ergonomic
      analysis of the driver's workplace in an electric locomotive. It presents the
      structure of the diagnosis and its assumptions, and includes a re-evaluation of
      the questionnaire-expert method in ergonomic research. The article presents
      research data on weights and evaluations including their standard deviations for
      particular priority features. Ergonomic levels of the studied operator's cabin in
      locomotives are compared.

PMID- 12067513
TI  - An evaluation of the NIOSH Lifting Equation: a psychophysical and biomechanical
      investigation.
AB  - Using the results of psychophysical and biomechanical experiments, NIOSH
      (National Institute for Occupational Safety and Health) Recommended Weight Limit
      (RWL), the Lifting Index (LI), the form of the asymmetry multiplier, and the
      criterion for compression force were investigated. Analysis of the results
      indicated a significant difference between the NIOSH RWL and the reported Maximum
      Acceptable Weight of Lift (MAWL). Contrary to the NIOSH lifting equation, the
      form of the asymmetry multiplier was found to be non-linear. The overall average
      of peak compression force on the L5/S1 was 3685 N. Fifty-eight percent of all
      compression forces reported in the biomechanical experiment were found to exceed
      the suggested 3400 N set by NIOSH guidelines. These results support previous
      research findings on the validity of NIOSH guidelines.

PMID- 12067514
TI  - The relationships between biomechanical and postural stresses, musculoskeletal
      injury rates, and perceived body discomfort experienced by industrial workers: a
      field study.
AB  - A combination of archival, subjective, and observational field data collection
      methods were used to investigate the relationship between biomechanical and
      postural stresses, and the resulting physical strain experienced by industrial
      workers of a packaging plant. Assessment of physical strain was based on the
      number and incidence rate of Occupational Safety and Health Administration (OSHA)
      reportable injuries that were recorded over a period of 27 months, and based on
      the self-reported ratings of perceived body discomfort. Both the biomechanical
      and postural stresses correlated with the musculoskeletal injury rate. The
      results illustrate the usefulness of postural and biomechanical analyses for
      assessing the risk of injury in industry.

PMID- 12067515
TI  - Effects of gender and athletic participation on driving capability.
AB  - This study sought to determine if spatiotemporal skills, represented by success
      in high level sport, transfer to driving and, if so, whether such transfer is
      mediated by the gender of the driver. Using an emergency-braking test, we
      compared the driving ability of male and female athletes and non-athletes and
      showed that athletes achieved significantly longer and therefore superior
      durations for time-to-contact. The advantage of athletic participation thus did
      not appear in movement time but rather in the ability to produce desirable
      performance in context. We found that males and females did not differ
      significantly with respect to driving, however, involvement in sport apparently
      transfers to aspects of driving and so provides benefits beyond the intrinsic
      reward of the sports activities themselves.

PMID- 12067516
TI  - The basic principles of building an ergonomic component of automated training
      systems.
AB  - In recent years, in view of the transformation in education in the Russian
      Federation, it has been necessary to introduce different technical facilities and
      new educational methods into the educational process. An introduction of training
      systems into the educational process concerns every educational method. New
      methods use various results from such fields as pedagogy, psychology,
      cybernetics, mathematics, and linguistics. Automated training systems consist of
      3 components: informational, didactic, and ergonomic. This paper considers 2
      components: didactic and ergonomic. They provide maximum learning with minimum
      energy consumption on the part of the trainee, in acceptable working conditions.
      As an example, this paper considers educational systems of calculus mathematics
      and mathematical geophysics realized in the Novosibirsk State University and
      Institute, Russian Federation.

PMID- 12067517
TI  - Bioconversion of water-hyacinth (Eichhornia crassipes) hemicellulose acid
      hydrolysate to motor fuel ethanol by xylose-fermenting yeast.
AB  - Water-hyacinth (Eichhornia crassipes) hemicellulose acid hydrolysate has been
      utilized as a substrate for ethanol production using Pichia stipitis NRRL Y-7124.
      Hydrolysate fermentability was considerable improved by boiling, and overliming
      up to pH 10.0 with solid Ca(OH)(2) in combination with sodium sulfite. The
      percent total sugar utilized and ethanol yield (Y(p/s)) for the untreated
      hydrolysate were 20.15+/-0.17% and 0.19+/-0.003 g(p) g(s)(-1), respectively,
      compared with 76.0+/-0.32% and 0.35 g(p) g(s)(-1), respectively for the treated
      material. The fermentation was very effective at an aeration rate of 0.02 v/v/m,
      temperature 30+/-0.2 degrees C and pH 6.0+/-0.2. However, the volumetric
      productivity (Q(p)) was still considerably less than observed in a simulated
      synthetic hydrolysate medium with a sugar composition similar to the
      hemicellulose acid hydrolysate. L-Arabinose was not fermented but assimilated.
      The presence of acetic acid in the hydrolysate decreased the ethanol yield and
      productivity considerably.

PMID- 12067518
TI  - Efficient lipase catalysed production of a lubricant and surfactant formulation
      using a continuous solvent-free process.
AB  - The transesterification of sunflower oil with a high oleic acid residue content
      (typically 83.5%) with butanol-1 by immobilised Lipozyme was carried out in a
      solvent free system and in a continuous way. During the first 6 h of reactor
      operation, a transition phase was observed, in which the main products were butyl
      ester and glycerol. This latter being insoluble in the reaction mixture, it is
      adsorbed onto the enzyme support thus leading to a decrease in enzyme
      performance. Step by step, less and less glycerol is produced and finally when
      glycerol is no longer produced a steady state is attained. The product
      composition is a mixture of butyl ester (65 molar%), monoglyceride (26 molar%),
      diglyceride (6 molar%) and residual triglyceride (3 molar%). This mixture has
      interesting lubricant and surfactant properties. The reactor was maintained
      without any loss in activity for a period of 3 months. This result is very
      different to that obtained using an organic solvent (n-hexane) which leads to a
      total loss of enzyme activity within a few hours.

PMID- 12067519
TI  - Effects of culture conditions on the production of polyhydroxyalkanoates by
      Azotobacter chroococcum H23 in media containing a high concentration of alpechin
      (wastewater from olive oil mills) as primary carbon source.
AB  - Large amounts of homopolymers containing beta-hydroxybutyrate (PHB) and
      copolymers containing beta-hydroxyvalerate (P[HB-co-HV]) are produced by
      Azotobacter chroococcum strain H23 when growing in culture media amended with
      alpechin (wastewater from olive oil mills) as the sole carbon source. Copolymer
      was formed when valerate (pentanoate) was added as a precursor to the alpechin
      medium, but it was not formed with the addition of propionate as a precursor. A.
      chroococcum formed homo- and copolymers of polyhydroxyalkanoates (PHAs) up to 80%
      of the cell dry weight, when grown on NH(4)(+)-medium supplemented with 60% (v/v)
      alpechin, after 48 h of incubation at 100 rev min(-1) and 30 degrees C.
      Production of PHAs by strain H23 using alpechin looks promising, as the use of a
      cheap substrate for the production of these materials is essential if bioplastics
      are to become competitive products.

PMID- 12067520
TI  - Optimizing high strength acetic acid bioprocess by cognitive methods in an
      unsteady state cultivation.
AB  - Methods of adapting micro-organisms to an inhibiting factor in an active
      industrial bioprocess were examined with an acetic acid fermentation as model.
      With the aim of automatic control, a fuzzy-logic system was developed on the
      basis of the collected knowledge of skilled vinegar brewers. In a first step,
      this fuzzy system was to assess the actual adaptation degree of the bacteria on
      the basis of data from robust and reasonably priced sensors. From this
      information an appropriate setpoint value for the inhibiting factor 'final acid
      concentration' was derived for each batch cycle. As a result a further acid
      tolerance was found after several batch cycles. This adaptation effect should be
      used to increase the product concentration to more than 20 g per 100 ml acetic
      acid with a high productivity. The stepwise adapted culture was productive over
      the aimed acetic acid concentration, a 10% improvement of the product formation
      rate could be found compared with the status before conditioning. High product
      concentration and increased productivity finally result in shorter cycle times,
      less transport and storage volumes, an improved utilization of energy and
      material resources, and, last but not least, they are an essential steps towards
      the fulfillment of economical and ecological demands.

PMID- 12067521
TI  - A generic model for changes in microbial kinetic coefficients.
AB  - Acclimation patterns in kinetic coefficients clearly demonstrate the limits of
      Monod's theory for the mathematical description of microbial growth. Focusing on
      E. coli grown under variable glucose levels, these patterns turn out to be highly
      diverse and sometimes even contradictory. Here, a new model based on an
      optimisation assumption is applied to a spectrum of adaptation phenomena, which
      are observed at steady-state as well as during transient situations. On the level
      of apparent kinetic coefficients, rates of adaptation are calculated depending on
      differential growth benefits. The resulting dynamics is bounded since maximum
      growth rate and substrate affinity are related by a non-linear trade-off. Long
      term effects of phenotypic and genotypic changes under glucose limitation are
      robustly predicted by the model and explained in terms of their adaptive
      significance. Equivocal short-term recovery patterns occurring after sudden
      substrate excess are traced back to differences in the internal physiological
      state of the cells which in turn can be calculated in dependence on the inoculum
      history. Metabolic stress is a second determinant of short-term variations in
      kinetic coefficients which is here quantified in relation to external conditions
      as well as the internal state of cells. We demonstrate that lag phenomena and
      oscillations in anabolic activity exercised by E. coli under continuous growth
      acceleration can be reproduced without formulations being explicit in lag
      periods, metabolite concentrations or the timing of experimental changes. The
      overall predictive power of the simple approach indicates that slow as well as
      fast adjustments in apparent kinetic characteristics are strongly related to a
      dynamic optimisation strategy.

PMID- 12067522
TI  - Population analysis of a binary bacterial culture by multi-parametric flow
      cytometry.
AB  - To study the degradation of a xenobiotic that requires a mixed culture it is
      essential to monitor the proportions and to control the population dynamics of
      the component strains. For these purposes fluorochromising techniques and multi
      parametric flow cytometry were used to follow Rhodococcus erythropolis K2-3 and
      Ochrobactrum anthropi K2-14, both of which are needed to degrade 4-(2,4
      dichlorophenoxy)butyric acid (2,4-DB). Although the two strains can grow in
      constant proportions in mixed cultures on other substrates, 2,4-DB could not be
      degraded as a sole substrate in a continuous process and R. erythropolis K2-3 was
      clearly impaired in the binary mixture. Addition of a second, easily assimilable
      substrate (xylitol) in appropriate concentrations (empirically determined) helped
      this strain survive, and thus facilitated complete degradation of the xenobiotic.
      This combination of substrates was found to stabilise the growth of R.
      erythropolis K2-3 and, consequently promoted the action of O. anthropi K2-14.
      Thus, the two organisms became established in constant proportions in a
      continuous process until reaching steady state. Consequently, multiplication and
      cell division activities of the two components of the binary culture were high
      and reached similar values to those attained when they are grown in pure culture.

PMID- 12067523
TI  - Studies on the catalytic behaviour of a cholinesterase-like abzyme in an AOT
      microemulsion system.
AB  - The hydrolytic activity of a monoclonal catalytic antibody (9A8) (abzyme) with
      acetylcholinesterase-like activity was investigated in water-in-oil (w/o)
      microemulsions (reverse micelles) based on sodium bis-2
      (ethylhexyl)sulfosuccinate (AOT) in isooctane, using p- and o-nitrophenylacetate
      (p-and o-NPA) as substrates. The dependence of the abzyme hydrolytic activity on
      the molar ratio of water to surfactant (w(o)) showed a bell-shaped curve,
      presenting a maximum at w(o)=11.1. An increase of the AOT concentration at
      constant w(o), resulted in a decrease of the catalytic activity suggesting a
      possible inhibition effect of the surfactant. The incorporation of the abzyme
      into the reverse micelle system caused a blue shift of the fluorescence emission
      maximum by a magnitude of 7-10 nm depending on the w(o) value. This result
      indicates that the antibody molecule, or a large part of it, is located in the
      aqueous microphase of the system. Kinetic studies showed that the hydrolysis of p
      and o-NPA in microemulsion system as well as in aqueous solution follows
      Michaelis-Menten kinetics. The catalytic efficiency (k(cat)/K(m)) in w/o
      microemulsion was significant lower than in aqueous solution.

PMID- 12067524
TI  - Enzymatic characterization of a recombinant isoform hybrid of glutamic acid
      decarboxylase (rGAD67/65) expressed in yeast.
AB  - BACKGROUND AND AIMS: Glutamic acid decarboxylase (GAD, EC 4.1.1.15) catalyses the
      conversion of glutamate to gamma-aminobutyric acid (GABA). The 65 kDa isoform,
      GAD65 is a potent autoantigen in type 1 diabetes, whereas GAD67 is not. A hybrid
      cDNA was created by fusing a human cDNA for amino acids 1-101 of GAD67 to a human
      cDNA for amino acids 96-585 of GAD65; the recombinant (r) protein was expressed
      in yeast and was shown to have equivalent immunoreactivity to mammalian brain GAD
      with diabetes sera. We here report on enzymatic and molecular properties of
      rGAD67/65. METHODS: Studies were performed on enzymatic activity of rGAD67/65 by
      production of 3H-GABA from 3H-glutamate, enzyme kinetics, binding to the enzyme
      cofactor pyridoxal phosphate (PLP), stability according to differences in pH,
      temperature and duration of storage, and antigenic reactivity with various GAD
      specific antisera. RESULTS: The properties of rGAD67/65 were compared with
      published data for mammalian brain GAD (brackets). These included a specific
      enzyme activity of 22.7 (16.7) nKat, optimal pH for enzymatic activity 7.4 (6.8),
      K(m) of 1.3 (1.3) mM, efficient non-covalent binding to the cofactor PLP, and
      high autoantigenic potency. The stability of rGAD67/65 was optimal over 3 months
      at -80 degrees C, or in lyophilized form at -20 degrees C. CONCLUSIONS: Hybrid
      rGAD67/65 has enzymatic and other properties similar to those of the mixed
      isoforms of GAD in preparations from mammalian brain as described elsewhere, in
      addition to its previously described similar immunoreactivity.

PMID- 12067525
TI  - Enhanced separation of filamentous fungi by ultrasonic field: possible usage in
      repeated batch processes.
AB  - Usage of ultrasonic field-based filters in retention of filamentous fungal cells
      was assessed using Rhizopus arrhizus NRRL 1526 as a model organism. Effects of
      operating conditions, such as power input, harvest pump flow rate, run time and
      stop time, on the system's separation efficiency (SE) were evaluated by
      modulating the variables according to a Central Composite Design (CCD). The
      standard pump with which the ultrasonic filter was equipped was shown to be
      unsuitable and was, therefore, substituted for with a prime rate reverse pump
      that made possible separation and recycle of the mycelial biomass. The operating
      conditions were optimised (run time, 300 s; stop time, 3 s; power input, 6 W;
      harvest pump flow rate, 4 l per day) and a repeated batch process (three batches
      for a total of 192 h) was performed during which the SE was maintained always
      higher than 88%.

PMID- 12067526
TI  - Protruding aortic plaque - a time to define a unique clinical entity.

PMID- 12067527
TI  - Echocardiographic evaluation of the left atrial appendage; only a prerogative of
      transoesophageal echocardiography?

PMID- 12067528
TI  - Mechanism of TMR; the debate continues.

PMID- 12067529
TI  - Visualization of left atrial appendage and assessment of its function by
      transthoracic second harmonic imaging and contrast-enhanced pulsed Doppler.
AB  - BACKGROUND: Low flow velocity within the left atrial appendage, as assessed by
      transoesophageal echocardiography, is a predictor of thromboembolism and of a low
      success rate of cardioversion of atrial fibrillation. However, the semi-invasive
      nature does limit its serial application as a screening technique. METHODS AND
      RESULTS: We investigated the value of transthoracic second harmonic
      echocardiography and pulsed Doppler at baseline and after intravenous contrast
      injection to visualize the left atrial appendage and assess blood flow velocities
      within its cavity. We studied 51 consecutive patients undergoing transoesophageal
      echocardiography. After transoesophageal echocardiography, transthoracic second
      harmonic imaging was performed and the left atrial appendage was visualized in 46
      patients. Interpretable pulsed Doppler tracings of left atrial appendage flow
      were obtained at baseline in 39 patients and in 45 patients during Levovist
      administration. The correlations between peak emptying velocity of left atrial
      appendage as measured by transoesophageal echocardiography and by transthoracic
      standard and contrast-enhanced Doppler were 0.81 and 0.91, respectively. The
      agreement between transoesophageal echocardiography and transthoracic contrast
      enhanced pulsed Doppler echocardiography in classifying left atrial appendage
      flow velocity patterns was 93%. Left atrial appendage thrombus was detected by
      transthoracic second harmonic imaging in only one of the eight patients shown by
      transoesophageal echocardiography to have a thrombus. However, all but one of the
      patients with left atrial appendage thrombus and/or spontaneous echocardiographic
      contrast at transoesophageal echocardiography had <30cm/s left atrial appendage
      flow velocity by transthoracic Doppler. CONCLUSIONS: This study shows that left
      atrial appendage can be visualized by transthoracic second harmonic imaging and
      that the flow velocity within its cavity is reliably measured by pulsed Doppler
      in a substantial fraction of patients. Contrast enhancement improves the
      feasibility and the accuracy of transthoracic evaluation of left atrial appendage
      flow velocity. The practical value of these results in predicting thromboembolic
      risk and success of cardioversion of atrial fibrillation needs to be proved by
      prospective studies.

PMID- 12067530
TI  - Contrast-echocardiography: confirmation of patency of laser channels after
      transmyocardial laser revascularization.
AB  - AIMS: Apart from casuistic autopsy results there is no long-term evidence for
      channel perfusion after transmyocardial laser revascularization in humans.
      METHODS AND RESULTS: Fifteen consecutive patients aged 63+/-17 years were
      investigated 71+/-15 days after coronary artery bypass surgery and/or
      transmyocardial revascularization with 13-37 (20+/-5) channels (CO(2) laser, 40
      J/pulse). Echocardiography was performed after injection of 6 ml echo contrast
      medium into left ventricular cavity and after injection of 3 ml contrast medium
      into the left main coronary artery. In five patients with additional bypass
      surgery to the same region, we also injected 3 ml contrast medium into bypass
      graft. We could prove in 10 of 15 patients (67%) one or two laser channels in the
      apical left ventricular myocardium. Channels were perfused exclusively during
      systole. During following heart cycles myocardium was opacified up to a mean
      width of 1.4+/-0.4 cm, a mean depth of 0.71+/-0.1cm, and a mean area of 1.0+/-0.6
      cm(2). Contrast medium was washed out via coronary venous system in 9+/-8
      systoles. CONCLUSION: This is the first clinical evidence of long-term laser
      channel patency in humans showing perfused myocardium via left ventricular
      cavity.

PMID- 12067531
TI  - Intra- and inter-observer reproducibility of transthoracic pulmonary venous
      Doppler flow indices after acute myocardial infarction.
AB  - AIMS: To examine the intra- and inter-observer reproducibility of pulmonary
      venous flow indices in patients with acute myocardial infarction. METHODS: Two
      investigators, blinded to the results of the other examination, each examined 28
      clinically stable post infarction patients in sinus rhythm. The two stored
      digital Doppler recordings from each patient were analysed in a blinded manner by
      both investigators to obtain the intra- and inter-observer reproducibility
      including both a new recording and new measurements. RESULTS: The intra- and
      inter-observer coefficients of variation for the different variables ranged
      between 5-15% and 8-23% respectively. For some of the indices there was a
      difference in means between the observers, and the indices were influenced in
      different degree by a new measurement and new recording. The degree of
      variability found in this study indicates wide relative limits of agreement,
      ranging from +/-10% to +/-45%. CONCLUSION: The reproducibility of pulmonary
      venous flow indices was only moderate with relatively wide limits of agreement.
      The reproducibility was, however, comparable to other echocardiographic
      measurements of left ventricular dimensions and function.

PMID- 12067532
TI  - Left atrial appendage function in patients with mitral stenosis in sinus rhythm.
AB  - AIMS: Left atrial appendage thrombi are believed to be the source of embolism in
      patients with rheumatic mitral stenosis in atrial fibrillation. There are a few
      studies which search the effects of left atrial appendage dysfunction in patients
      with mitral stenosis in sinus rhythm. METHODS AND RESULTS: Left atrial appendage
      function and flow patterns in 41 patients with rheumatic mitral stenosis in sinus
      rhythm and 11 healthy subjects were studied by transoesophageal echocardiography.
      Left atrial appendage flow profiles were recorded within the proximal third of
      the appendage. The left atrial appendage ejection fraction was expressed as
      (maximal area of appendage minimal area of appendage)/maximal area of appendage.
      In addition, two-dimensional imaging was used to determine the presence of
      spontaneous echocardiographic contrast and thrombus formation. Patients with
      mitral stenosis in sinus rhythm had significantly decreased left atrial appendage
      emptying and filling velocities compared to controls (0.40+/-0.15m/s vs 0.82+/
      0.19 m/s and 0.42+/-0.21 m/s vs 0.68+/-0.28, respectively, P<0.001 and P<0.05).
      Compared with the control subjects, patients with mitral stenosis had
      significantly greater maximal area of the appendage and had reduced left atrial
      appendage ejection fraction (5.3+/-2.2 cm(2) vs 2.4+/-0.5 cm(2) and 50+/-16% vs
      70+/-7%, respectively, P<0.001 and P<0.05). Of the patients with mitral stenosis
      in sinus rhythm, seven patients had spontaneous echocardiographic contrast and
      one of these had left atrial appendage thrombus. Compared with patients without
      spontaneous echocardiographic contrast, patients with spontaneous
      echocardiographic contrast had decreased left atrial appendage ejection fraction
      (33+/-21% vs 54+/-13%,P <0.01). One of the patients with mitral stenosis had
      central retinal artery occlusion, but thrombus was not observed in left atrial
      appendage. CONCLUSION: The study found that left atrial appendage dysfunction may
      occur in patients with mitral stenosis in sinus rhythm.

PMID- 12067533
TI  - Consistency of echocardiographic ejection fraction: variation and 'drift' by
      interpreter and practice site.
AB  - AIMS: Visual analysis of ejection fraction by echocardiography (echo) is commonly
      performed, but little data exists regarding consistency among interpreters. We
      postulate that an active echo group evolves a standard to which interpreters
      cluster, with variation or 'drift' occurring at satellite sites distant from the
      main practice centre. Assuming that echo ejection fraction follows a normal
      distribution, average ejection fraction for high volume readers should be
      similar. METHODS AND RESULTS: From May 1997 to June 1999, 8187 echoes were read
      by 16 (average 512) readers of a single practice at several sites. Composite and
      individual ejection fraction (visual estimate) means and standard deviations were
      compared. Composite ejection fraction was 54.17+/-11.35. Mean ejection fraction
      varied significantly overall among readers (P<0.0001) with 37 comparisons between
      individual readers being significantly different (P<0.05). However, analysis
      suggested that these individual differences involved only five readers, four of
      whom practised at satellite sites. If these five readers were excluded, no
      significant individual differences were seen (n=6202). If only the four satellite
      readers were excluded, just four significant individual differences were seen
      (n=6915). CONCLUSIONS: (1) Within a busy single practice site, mean echo ejection
      fraction is very similar, suggesting a self-evolved practice standard that is
      consistently adhered to. (2) 'Drift' or variability is seen at smaller satellite
      sites, perhaps due to less exposure to the echo interpretations of others. (3)
      This type of analysis may provide a useful quality assurance tool for echo
      laboratories.

PMID- 12067534
TI  - Doppler characterization of left ventricular diastolic function in beta
      thalassaemia major. Evidence for an early stage of impaired relaxation.
AB  - AIMS: Doppler echocardiographic studies of left ventricular diastolic function in
      patients with thalassaemia major have shown conflicting findings. This study was
      undertaken to compare Doppler echocardiographic parameters of diastolic function
      among a group of patients with thalassaemia major, a group with thalassaemia
      intermedia and a group of normal individuals. METHODS AND RESULTS: 50 patients
      with thalassaemia major, 38 patients with thalassaemia intermedia and 29 normal
      subjects were studied. All had normal systolic function. The thalassaemia
      intermedia patients had larger body surface area and left ventricular mass index
      than the thalassaemia major patients but less than the controls. The ratios
      between peak early and late mitral diastolic flow (E/A ratio) were comparable
      between the three groups. The haematocrit levels were comparable in the two study
      groups, but the ferritin levels were significantly higher in the thalassaemia
      major group (P<0.001). Using multiple regression analysis to correct for the
      influence of heart rate, age and body surface area, we found a prolonged
      isovolumic relaxation time (P<0.03) and a lower E wave (P<0.001) in the
      thalassaemia major group as compared to the thalassaemia intermedia group. The
      isovolumic relaxation time also differed significantly between the thalassaemia
      groups and the control (P<0.001), suggesting a state of impaired relaxation most
      notable in thalassaemia major that is probably due to iron overload. CONCLUSION:
      In patients with thalassaemia major and normal systolic function who have iron
      overload, the earliest sign of diastolic dysfunction is an impairment in left
      ventricular relaxation manifested as a prolonged isovolumic relaxation time.

PMID- 12067535
TI  - Striking effect of left ventricular high filling pressure with mitral
      regurgitation on mitral annular velocity during early diastole. A study using
      colour M-mode tissue Doppler imaging.
AB  - AIMS: To evaluate the effect of considerably high left ventricular filling
      pressure with mitral regurgitation on mitral annular velocity during early
      diastole. SUBJECTS: Two hundred and forty-three patients who underwent cardiac
      catheterization for evaluation of chest pain. METHODS: Mitral annular velocity
      during early diastole was measured by colour M-mode tissue Doppler imaging.
      Patients were divided into the following three groups according to the cardiac
      catheterization data. Group A (n=147): patients having left ventricular
      relaxation time constant tau<46 ms and left ventricular end-systolic volume index
      <38 ml m(-2); group B (n=88): patients having tau>or=46 ms and/or end-systolic
      volume index >or=38 ml m(-2); group C (n=8): patients having mean pulmonary
      capillary wedge pressure >or=16 mmHg in addition to tau>or=46 ms and end-systolic
      volume index >or=38 ml m(-2). RESULTS: Mitral annular velocity during early
      diastole was significantly less in group B (4.8+/-1.4 cm s(-1)) than in group A
      (7.7+/-1.9 cm s(-1)). However, there was no significant difference between groups
      A and C (8.3+/-0.8 cm s(-1)). A transmitral E/A >1.0 was observed in 12/147
      patients of group A, 10/88 of group B, and 8/8 of group C. The incidence of
      >or=Sellers' grade II mitral regurgitation was higher in group C than the others.
      CONCLUSIONS: A paradoxically faster mitral annular velocity during early diastole
      is found in patients having left ventricular dysfunction with moderate to severe
      mitral regurgitation and considerably high left ventricular filling pressure.
      Attention should be paid to an interpretation of mitral annular velocity during
      early diastole regarding left ventricular early diastolic performance in patients
      having mitral regurgitation with an E/A >1.0 in their transmitral flow.

PMID- 12067536
TI  - Vasodilator stress echocardiography for risk stratification of medically
      stabilized unstable angina.
AB  - AIMS: The aims of this study were to assess the safety, feasibility and
      prognostic value of dipyridamole-atropine stress echo in patients with medically
      stabilized unstable angina. METHODS: The initial population consisted of 173
      patients consecutively admitted at two different Coronary Care Units with class
      IIIB unstable angina. Of these, 56 were excluded: five had poor acoustic window,
      24 did not stabilize with medical therapy and underwent urgent coronary
      angiography, 26 evolved in non-Q wave myocardial infarction and one patient died.
      The remaining 117 patients underwent dipyridamole-atropine stress echo after 48 h
      without symptoms or electrocardiographic evidence of myocardial ischaemia.
      RESULTS: No complications or side effects occurred. An ischaemic response was
      found in 61 patients. During follow-up (10+/-9 months), three cardiac deaths,
      eight infarctions, 13 unstable anginas, and seven late (>3 months from stress
      testing) revascularizations occurred. There were 22 events (36%) in patients
      with, and nine events (16%) in patients without, inducible ischaemia (P=0.01). At
      Cox analysis peak-stress wall-motion score index (HR=5.5; 95% CI, 1.9 to 15.5;
      P=0.0015), and admission ST-segment depression (HR=4.2; 95% CI, 1.7 to 10.7;
      P=0.0022) were independent predictors of spontaneous events (cardiac death,
      infarction, unstable angina). The 12-month event-free survival was 69% for
      ischaemic and 83% for non-ischaemic group (P=0.03). In considering major events
      as end-points (spontaneous events, and late revascularization), again
      multivariate prognostic indicators were peak-stress wall-motion score index
      (HR=14.2; 95% CI, 2.6 to 76.6; P=0.0021), and admission ST-segment depression
      (HR=3.1; 95% CI, 1.4 to 6.9; P=0.0055). The 12-month event-free survival rate was
      58% for ischaemic and 81% for non-ischaemic group (P=0.002). With an interactive
      stepwise procedure, stress echo findings were found to provide incremental
      prognostic contribution to that of clinical data alone. CONCLUSIONS: With proper
      selection of patients, dipyridamole-atropine stress echo is extremely safe and
      feasible in patients with medically stabilized unstable angina, and can be useful
      in identification of subjects at risk for future cardiac events.

PMID- 12067537
TI  - Quantitative assessment of right ventricular volumes in severe chronic
      thromboembolic pulmonary hypertension using transthoracic three-dimensional
      echocardiography: changes due to pulmonary thromboendarterectomy.
AB  - AIMS: Evaluation of a three-dimensional reconstruction method to show the changes
      of right ventricular volume and systolic function when patients undergo pulmonary
      thromboendarterectomy for chronic thromboembolic pulmonary hypertension. METHODS
      AND RESULTS: In the examination of 11 patients (four female, seven male; age 56+/
      10 years) before and after pulmonary thromboendarterectomy, end-diastolic and end
      systolic right ventricular volumes were determined as a sum total of the
      calculated volumes of derived parallel slices of the right ventricle. Using a
      Tomtec workstation and a Vingmed CFM 800 echocardiography device, the acquired
      data were ECG-and respiration-triggered in the course of transthoracic
      examination, using step intervals of 5 degrees. The ventricular outline was
      traced manually on 5mm slices from longitudinal cut planes. For subsequent
      correction, their area measurements were displayed and the volume cross-checked
      against the volume from orthogonal cut planes. End-diastolic and end-systolic
      volumes could be quantified in 11/11 cases before surgery, but data could only be
      attained for 9/11 patients after surgery, because a limited apical window
      rendered the postoperative three-dimensional reconstruction impossible in two
      cases. Before surgery, right ventricular size was larger than normal and systolic
      function was clearly impaired in all of the patients (end-diastolic volume: 121+/
      37 ml; end-systolic volume 91+/-30 ml; ejection fraction 25+/-8%). The decrease
      in mean pulmonary artery pressure after surgery was significant (47+/-8 vs 26+/-8
      mmHg; P<0.05). End-diastolic and end-systolic right ventricular volumes had been
      reduced (80+/-33 ml and 54+/-31 ml respectively), and the ejection fraction had
      increased (36+/-9%). CONCLUSIONS: Successfully performed pulmonary
      thromboendarterectomy leads to a significant reduction of right ventricular
      chamber size and improvement of systolic function, which can be determined with
      great precision and quite easily, using transthoracic three-dimensional
      echocardiography. Published by Elsevier Science Ltd. All rights reserved.

PMID- 12067538
TI  - Non-invasive estimation of left ventricular filling pressures by Doppler
      echocardiography.

PMID- 12067539
TI  - A dyspnoeic patient.

PMID- 12067540
TI  - Antifungal Sordarins. Part 4: synthesis and structure--activity relationships of
      3',4'-fused alkyl-tetrahydrofuran derivatives.
AB  - A series of Sordarin derivatives bearing alkyl substituted tetrahydrofuran rings
      fused to C3'-C4' bond of the sugar moiety have been prepared and their antifungal
      properties evaluated. Most of them show remarkable antifungal activity against
      Candida spp and Cryptococcus neoformans.

PMID- 12067541
TI  - Antimalarial activities of ring-substituted bioimidazoles.
AB  - We report in vitro antimalarial activities against chloroquine sensitive and
      resistant Plasmodium falciparum strains, and in vivo activities against
      Plasmodium berghei in mice for four series of ring-substituted-L-histidines and
      histamines.

PMID- 12067542
TI  - Synthesis and evaluation of N-substituted 1,4-oxazepanyl Sordaricins as selective
      fungal EF-2 inhibitors.
AB  - Sordaricin analogues possessing 6-methoxy-7-methyl-1,4-oxazepane moiety instead
      of the sugar part were synthesized and evaluated. It was found that N
      substituents on the oxazepane ring had influence on biological activity. In
      particular, N-(2-methylpropenyl) derivative 12p exhibited potent in vitro
      antifungal activity. Furthermore, 12p maintained significant activity (MIC 0.25
      microg/mL) against Candida albicans SANK51486 even in the presence of 20% horse
      serum.

PMID- 12067543
TI  - Design, synthesis, and evaluation of postulated transient intermediate and
      substrate analogues as inhibitors of 4-hydroxyphenylpyruvate dioxygenase.
AB  - An epoxybenzoquinone, 4-hydroxyphenoxypropionic acid, and 2-hydroxy-3-phenyl-3
      butenoic acid derivatives have been designed, synthesized, and evaluated for in
      vitro inhibition activity against 4-hydroxyphenylpyruvate dioxygenase (4-HPPD)
      from pig liver by the spectrophotometric enol-borate method. The biological data
      demonstrated that neither epoxybenzoquinone ester nor 2-hydroxy-3-phenyl-3
      butenoic acid is an inhibitor of 4-HPPD. The most potent 4-HPPD inhibitor tested
      was 3-hydroxy-4-phenyl-2(5H)-furanone with an IC(50) value of 0.5 microM, which
      may serve as a lead compound for further design of more potent 4-HPPD inhibitors.

PMID- 12067544
TI  - New ketosteroids from the red alga Hypnea musciformis.
AB  - The dichloromethane/methanol extract from the red alga Hypnea musciformis
      exhibited PPE elastase inhibition. A diketosteroid, the 20-hydroxy-5alpha-cholest
      22-ene-3,6-dione was responsible for this activity. Two new steroids were
      isolated, 2 was assigned as the 6alpha-hydroxy-cholest-4-ene-3-one and 3 as the
      6alpha-hydroxy-cholest-4,22-diene-3-one. The structures were assigned mainly on
      the basis of 1H and 13C NMR experiments.

PMID- 12067545
TI  - Pyrrolidine-5,5-trans-lactams as novel mechanism-based inhibitors of human
      cytomegalovirus protease. Part 3: potency and plasma stability.
AB  - Mechanism-based inhibitors of HCMV protease, which are stable to human plasma (>
      or = 20 h) and have single-figure potency in the microM range against HCMV
      protease, have been developed based on the dansylproline alpha-methyl pyrrolidine
      5,5-trans-lactam nucleus.

PMID- 12067546
TI  - A convenient synthetic pathway for multivalent assembly of aminoglycoside
      antibiotics starting from amikacin.
AB  - Vinylpolymers carrying a kanamycin cluster at the side chain were prepared via
      regioselective N-acylation of amikacin with N-succinimidyl p-vinylbenzoate,
      followed by radical homo- and co-polymerization with acrylamide. Two independent
      biological assays disclosed that the polyvalent kanamycin models showed neither
      antibacterial activity nor inhibitory activity against rRNA-based protein
      synthesis, suggesting that the multivalency-binding approach is not valid for
      integrating the potential of aminoglyoside anitibiotics.

PMID- 12067547
TI  - Synthesis of triazole-Tethered pyrrolidine libraries: novel ECE inhibitors.
AB  - The solid-phase synthesis of substituted 1,2,4-triazoles tethered to a 4
      mercaptopyrrolidine core 1 is described. This novel class of non-peptidic, Zn(2+)
      metallo-protease inhibitors was found to have inhibitory activity for the
      endothelin converting enzyme (ECE-1). The SAR of the substitution pattern in 1 is
      discussed.

PMID- 12067548
TI  - A new lipophilic fluorescent probe for interaction studies of bioactive
      lipopeptides with membrane models.
AB  - The new fluorescent lipophilic moiety 11-[(7-amino-4-methyl-2-oxo-2H-1-benzopyran
      3-acetyl)amino]undecanoic acid (AMCA-omegaAud-OH) was introduced by SPPS at the N
      terminus of the immunodominant epitope GpMBP(74-85). FRET experiments using the
      new fluorescent lipopeptide demonstrate that the peptide interacts with much more
      affinity with the membrane compared to the lipid free analogue.

PMID- 12067549
TI  - Efficient chemoenzymatic synthesis of (S)- and (R)-5-(1-aminoethyl)-2
      (cyclohexylmethoxy)benzamide: key intermediate for Src-SH2 inhibitor.
AB  - A facile chemoenzymatic synthesis of both the S and R forms of 5-(1-aminoethyl)-2
      (cyclohexylmethoxy)benzamide a key intermediate of non-peptidic Src SH2
      inhibitors is described. Both the enantiomers were synthesized in high optical
      purity (>99% ee) by reduction followed by lipase-mediated acylation of the
      precursor 6 in one-pot. Immobilized Pseudomonas cepacia lipase offered high
      degree of enantioselectivity with spontaneity.

PMID- 12067550
TI  - Synthesis and antifungal activity of the 2,2,5-tetrahydrofuran regioisomers of
      SCH 51048.
AB  - The four 2,2,5-regioisomer counterparts of SCH 51048 were synthesized and
      evaluated. As with the parent series, only the two cis isomers possessed any in
      vitro activity, and only the activity of the isomer with the R-configuration at
      the tetrahydrofuran 2-carbon was significant. The activity data suggests that
      oxygen at only one of the two possible ring positions benzylic to the
      difluorobenzene participates usefully in active site binding.

PMID- 12067551
TI  - Discovery of imidazole glycerol phosphate dehydratase inhibitors through 3-D
      database searching.
AB  - Imidazole glycerol phosphate dehydratase (IGPD) has become an attractive target
      for herbicide discovery since it is present in plants and not in mammals.
      Currently no knowledge is available on the 3-D structure of the IGPD active site.
      Therefore, we used a pharmacophore model based on known inhibitors and 3-D
      database searches to identify new active compounds. In vitro testing of compounds
      from the database searches led to the identification of a class of pyrrole
      aldehydes as novel inhibitors of IGPD.

PMID- 12067552
TI  - A library construction of 2,5-disubstituted pyrrole compounds by using
      solid/solution-phase syntheses.
AB  - Using solid- and solution-phase synthesis, a library of 2,5-disubstituted pyrrole
      compounds was constructed. This is the first report that Stetter reaction was
      applied to the solid-phase synthesis for C-C bond formation. Some of 2,5
      disubstituted pyrrole compounds showed the inhibitory activity of LPS-induced
      mouse B-lymphocyte proliferation.

PMID- 12067553
TI  - Side-chain homologation of nodulisporic acid: synthesis of potent new dienyl
      derivatives.
AB  - A series of new, diene-modified nodulisporic acid analogues (2) bearing diverse
      functionality at the 3"- and 4"-sites was efficiently prepared from the 3"
      aldehyde 3. Biological evaluation of these synthetic nodulisporic acid analogues
      for systemic flea efficacy identified potent compounds and further clarified the
      structural requirements for ectoparasite activity.

PMID- 12067554
TI  - 4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists I.
AB  - A series of novel 4,4-disubstituted cyclohexylamine based NK(1) antagonists is
      described. The effect of changes to the C(1)-C(4) relative stereochemistry on the
      cyclohexane ring and replacements for the flexible linker are discussed, leading
      to the identification of compounds with high affinity and good in vivo duration
      of action.

PMID- 12067556
TI  - Structure-based design and synthesis of HIV-1 protease inhibitors employing beta
      D-mannopyranoside scaffolds.
AB  - A preliminary account on the structure-based design, synthesis and evaluation of
      peptidomimetic inhibitors of HIV-1 protease containing beta-D-mannopyranoside
      scaffolds is given. The compounds prepared had IC(50) values in the micromolar
      range. The results provide a platform for the development of more potent
      carbohydrate-based inhibitors of HIV-1 and other aspartic proteases.

PMID- 12067555
TI  - 4,4-Disubstituted cyclohexylamine NK(1) receptor antagonists II.
AB  - A series of novel 4,4-disubstituted cyclohexylamines as NK(1) receptor
      antagonists is described: modifications to the amine moiety retain NK(1) receptor
      binding affinity whilst disrupting I(Kr) affinity.

PMID- 12067557
TI  - Discovery of potent and selective small molecule NPY Y5 receptor antagonists.
AB  - The discovery of a new class of sulfonamide NPY Y5 receptor antagonists is
      described. Optimization of this series led to the identification of compounds
      with high affinity for the hY5 subtype and excellent selectivity over the other
      NPY receptor subtypes. The SAR for this series was examined and a model for
      understanding the ligand-receptor interactions was developed.

PMID- 12067558
TI  - High-throughput synthesis optimization of sulfonamide NPY Y5 antagonists.
AB  - A series of sulfonamide neuropeptide Y Y5 antagonists was optimized by
      preparation of sets of analogues using high-throughput synthesis and purification
      techniques. Testing of these compounds for their ability to bind to the human NPY
      Y5 receptor revealed separate SAR trends for sulfonamide amides versus
      sulfonamide ureas versus sulfonamide amines. By understanding these SAR trends,
      potent compounds were identified in all three series.

PMID- 12067559
TI  - Discovery of substituted 3,4-diphenyl-thiazoles as a novel class of monoamine
      transporter inhibitors through 3-D pharmacophore search using a new pharmacophore
      model derived from mazindol.
AB  - Substituted 3,4-diphenyl-1,3-thiazols were identified as a class of novel and
      potent monoamine transporter inhibitors through a 3-D pharmacophore search using
      a new pharmacophore model derived from mazindol. The most potent compound (13)
      has K(i) values of 24 and 23 nM in binding to dopamine transporter and inhibition
      of dopamine reuptake, respectively.

PMID- 12067560
TI  - The synthesis and structure-activity relationships of 4-aryl-3-aminoquinolin-2
      ones: a new class of calcium-dependent, large conductance, potassium (maxi-K)
      channel openers targeted for post-stroke neuroprotection.
AB  - A series of 4-aryl-3-aminoquinoline-2-one derivatives was synthesized and
      evaluated as activators of the cloned maxi-K channel mSlo (hSlo) expressed in
      Xenopus laevis oocytes using electrophysiological methods. A brain penetrable
      activator of maxi-K channels was identified and shown to be significantly active
      in the MCAO model of stroke.

PMID- 12067561
TI  - CCR3 antagonists: a potential new therapy for the treatment of asthma. Discovery
      and structure-activity relationships.
AB  - CCR3 antagonist leads with IC(50) values in the microM range were converted into
      low nM binding compounds that displayed in vitro inhibition of human eosinophil
      chemotaxis induced by human eotaxin. In particular, 4-benzylpiperidin-1-yl-n
      propylureas and erythro-3-(4-benzyl-2-(alpha-hydroxyalkyl)piperidin-1-yl)-n
      propylureas (obtained via Beak reaction of N-BOC-4-benzylpiperidine) exhibited
      single digit nanomolar IC(50) values for CCR3.

PMID- 12067563
TI  - Impact of dietary factors on cancer causes and DNA integrity: new trends and
      aspects.

PMID- 12067564
TI  - Search for dietary antimutagens and anticarcinogens: methodological aspects and
      extrapolation problems.
AB  - It is well documented that dietary factors play a crucial role in the aetiology
      of human cancer and strong efforts have been made to identify protective
      (antimutagenic and anticarcinogenic) substances in foods. Although numerous
      studies have been published, it is problematic to use these results for the
      development of nutritional strategies. The aim of this article is a critical
      discussion of the pitfalls and problems associated with the search for protective
      compounds. The main obstacles in regard to the extrapolation of the data to the
      human situation arise from: (i) the use of inadequate experimental in vitro
      models, which do not reflect protective mechanisms in man and therefore give
      misleading results; (ii) the use of genotoxins and carcinogens that are not
      relevant for humans; (iii) the lack of knowledge about dose-effect relationships
      of DNA-protective and cancer protective dietary constituents; (iv) the use of
      exposure concentrations in animal models which exceed by far the human exposure
      levels; and finally (v) the lack of knowledge on the time-kinetics of protective
      effects. More relevant data can be expected from in vitro experiments with cells
      possessing inducible phase I and phase II enzymes, short-term in vivo models with
      laboratory animals which enable the measurement of effects in organs that are
      targets for tumour formation, and human biomonitoring studies in which endpoints
      are used that are related to DNA damage and cancer.

PMID- 12067565
TI  - Heterologous expression of human N-acetyltransferases 1 and 2 and
      sulfotransferase 1A1 in Salmonella typhimurium for mutagenicity testing of
      heterocyclic amines.
AB  - A variety of carcinogenic heterocylic amines (HAs) are found in cooked food. They
      can be metabolised to reactive intermediates via N-hydroxylation catalysed by
      cytochrome P450 1A2, followed by conjugation of the resulting N-hydroxyl group by
      N-acetyltransferase (NAT) or sulfotransferase (SULT). In order to compare the
      role of O-acetylation and O-sulfonation by human enzymes in the activation of
      HAs, we have introduced the cDNAs for wild-type forms of human NAT1, NAT2 and
      SULT1A1 in the acetyltransferase-deficient Salmonella typhimurium strain
      TA1538/1,8-DNP. Functional expression of recombinant proteins was demonstrated
      using immunoblot analysis and determination of enzyme activity with
      characteristic substrates. The established strains were used to study the
      mutagenicity of the N-hydroxy derivatives of 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). The
      results demonstrate that N-hydroxy-HAs are activated by different human enzymes.
      At the concentrations used in the mutagenicity assay, N-hydroxy-IQ was activated
      by human NAT2, but not by NAT1 or SULT1A1. In contrast, N-hydroxy-PhIP was
      activated specifically by human SULT1A1, but not by NAT1 or NAT2. Therefore, both
      O-acetylation and O-sulfonation by human enzymes have to be regarded as important
      determinants for HA genotoxicity in humans.

PMID- 12067566
TI  - DNA damage and metallothionein synthesis in human hepatoma cells (HepG2) exposed
      to cadmium.
AB  - Cadmium is an important heavy metal environmental toxicant, which is classified
      as a human carcinogen. The comet assay was used to evaluate the levels of DNA
      damage in a metabolically competent HepG2 cell line after treatment with low, non
      cytotoxic and physiologically relevant concentrations of cadmium, alone and in
      combination with the dietary mutagen 2-amino-3-methyl-imidazo[4,5-f]quinoline
      (IQ) and with the environmental mutagen benzo[a]pyrene (B(a)P). After exposure of
      the cells to 10, 100 and 1000 nM CdCl(2), a dose- and time-dependent increase of
      DNA damage was detected. Maximal damage was found after 12 h of treatment, but
      declined with further incubation with CdCl(2). The increased synthesis of
      metallothioneins on exposure to CdCl(2) up to 12 h suggests that they are
      responsible for the adaptation of HepG2 cells to the DNA damaging effects of
      CdCl(2). Co-treatment of the cells with CdCl(2) (10-1000 nM) and IQ (300 microM)
      induced a dose-dependent increase of DNA damage compared to cells treated with IQ
      alone. Co-genotoxic activity was also observed by increased formation of
      micronuclei in cells exposed to IQ and 1000 nM CdCl(2); at this concentration,
      CdCl(2) alone also induced micronuclei in HepG2 cells. Our results support the
      hypothesis that direct and indirect mechanisms are involved in cadmium-induced
      DNA damage.

PMID- 12067567
TI  - Protective effects of Brussels sprouts towards B[a]P-induced DNA damage: a model
      study with the single-cell gel electrophoresis (SCGE)/Hep G2 assay.
AB  - The aim of this study was to investigate the chemoprotective effects of Brussels
      sprouts juice towards benzo[a]pyrene (B(a)P)-induced DNA damage in the single
      cell gel electrophoresis (SCGE)/Hep G2 test system. This assay combines the
      advantages of the SCGE assay with that of the use of human-derived cells
      possessing inducible phase I and phase II enzymes. Co-treatment of Hep G2 cells
      with small amounts of Brussels sprouts juice (0.25-2.0 microl/ml) and B(a)P
      reduced the genotoxic effect of the latter in a dose-dependent manner. Contrary
      to the results with the crude juice, unexpected synergistic effects were observed
      with allyl isothiocyanate (AITC, 1.0-6.0 microM), a breakdown product of
      sinigrin, which is the most abundant glucosinolate in Brussels sprouts. Although
      these concentrations of AITC did not cause DNA damage per se, at higher
      concentrations (> or =25 microM), the compound caused a pronounced dose-dependent
      DNA damage by itself. Mechanistic studies showed that Brussels sprouts juice
      causes induction of activities of ethoxyresorufin O-deethylase (EROD) and
      glutathione S-transferase (GST) at dose levels which were protective towards
      B(a)P. In combined treatment experiments with (+/-)-anti-benzo[a]pyrene-7,8
      dihydrodiol-9,10-epoxide (BPDE, 5.0 microM), the main genotoxic metabolite of
      B(a)P, and Brussels sprouts juice, only weak protection was found indicating that
      the mechanism of chemoprotection of Brussels sprouts is not mediated through
      inactivation of this metabolite. In conclusion, our findings show that Brussels
      sprouts are highly protective against B(a)P-induced DNA damage in human-derived
      cells.

PMID- 12067568
TI  - Genotoxic effects of ochratoxin A in human-derived hepatoma (HepG2) cells.
AB  - Ochratoxin A (OTA) is a widespread mycotoxin that occurs in many commodities from
      grains to coffee beans all over the world. Evidence is accumulating that OTA may
      cause cancer in humans. The compound was tested in micronucleus (MN) and single
      cell gel electrophoresis (SCGE) assays in human-derived hepatoma (HepG2) cells
      and caused pronounced dose-dependent effects at exposure concentrations of 5
      microg/ml and greater. On the contrary, no induction of His(+) revertants was
      found in Salmonella microsome assays with strains TA98 and TA100 with HepG2
      derived enzyme (S9) mix in liquid incubation assays under identical exposure
      concentrations. Taken together, our results indicate that OTA is clastogenic in
      the human-derived cells. These findings support the assumption that this
      mycotoxin may cause genotoxic effects in hepatic tissue of humans.

PMID- 12067569
TI  - Anti-tumor promoting potential of selected spice ingredients with antioxidative
      and anti-inflammatory activities: a short review.
AB  - A wide variety of phenolic substances derived from spice possess potent
      antimutagenic and anticarcinogenic activities. Examples are curcumin, a yellow
      colouring agent, contained in turmeric (Curcuma longa L., Zingiberaceae), [6]
      gingerol, a pungent ingredient present in ginger (Zingiber officinale Roscoe,
      Zingiberaceae) and capsaicin, a principal pungent principle of hot chili pepper
      (Capsicum annuum L, Solanaceae). The chemopreventive effects exerted by these
      phytochemicals are often associated with their antioxidative and anti
      inflammatory activities. Cyclo-oxygenase-2 (COX-2) has been recognized as a
      molecular target of many chemopreventive as well as anti-inflammatory agents.
      Recent studies have shown that COX-2 is regulated by the eukaryotic transcription
      factor NF-kappaB. This short review summarizes the molecular mechanisms
      underlying chemopreventive effects of the aforementioned spice ingredients in
      terms of their effects on intracellular signaling cascades, particularly those
      involving NF-kappaB and mitogen-activated protein kinases.

PMID- 12067570
TI  - In vitro models for the identification and characterization of tumor-promoting
      and protective factors for colon carcinogenesis.
AB  - The present review aims to give a short overview of the existing cell culture
      models and their characteristics. While both the induction and the prevention of
      tumors can only be unequivocally demonstrated in vivo, in vitro models of
      colorectal cell growth are essential tools for the identification of candidate
      compounds and for the analysis of underlying mechanisms. Unfortunately normal and
      premalignant colorectal epithelial cells that represent the target cells of tumor
      promoters like desoxycholic acid or 1,2-diglyceride and could be used to
      investigate their cell biological effects are difficult to obtain. Cell line
      studies have mostly used carcinoma cell lines or rat small intestinal epithelial
      cells. Some normal immortalized cell lines have been established but are not
      widely used, and premalignant adenoma cell lines are extremely rare. However,
      those that do exist are useful both in mechanistic studies of cell growth and for
      the analysis of tumor promoters and chemoprotectors of colorectal carcinogenesis.

PMID- 12067571
TI  - Low iron state is associated with reduced tumor promotion in a two-stage mouse
      skin carcinogenesis model.
AB  - The purpose of this study was to investigate the effect of low iron state in a
      two-stage mouse skin carcinogenesis model using 7,12-dimethylbenz[a]anthracene
      (DMBA)-initiated and benzoyl peroxide (BPO)-promoted cutaneous tumorigenesis. All
      mice were treated with DMBA. Low iron state was achieved by injection with
      phenylhydrazine hydrochloride and feeding low iron diet. A low iron state
      resulted in a decrease in tumor incidence (papillomas and carcinomas) and number
      of tumors/mouse. Also, the conversion of papillomas to carcinomas was lower in
      mice on a low iron state. BPO treatment enhanced epidermal lipid peroxidation
      (LPO) and was accompanied by a depletion in the level of epidermal reduced
      glutathione (GSH) and decrease in the activities of antioxidant enzymes. BPO
      treatment also increased ornithine decarboxylase (ODC) activity and [3H]thymidine
      incorporation into cutaneous DNA. Mice in a low iron state were less susceptible
      to the effects of BPO treatment, as was apparent from a partial recovery of GSH
      levels and the activities of antioxidant enzymes, as well as a lower induction in
      ODC activity, [3H]thymidine incorporation into cutaneous DNA and lesser epidermal
      LPO. As expected, cutaneous iron levels were lower in mice on a low iron state.
      Thus, our data show that the tumor-promoting potential of BPO is reduced by low
      iron state in a two-stage mouse skin carcinogenesis model.

PMID- 12067572
TI  - Micronutrients and genomic stability: a new paradigm for recommended dietary
      allowances (RDAs).
AB  - Diet as a key factor in determining genomic stability is more important than
      previously imagined because we now know that it impacts on all relevant pathways,
      namely exposure to dietary carcinogens, activation/detoxification of carcinogens,
      DNA repair, DNA synthesis and apoptosis. Current recommended dietary allowances
      for vitamins and minerals are based largely on the prevention of diseases of
      deficiency such as scurvy in the case of vitamin C. Because diseases of
      development, degenerative disease and aging itself are partly caused by damage to
      DNA it seems logical that we should focus better our attention on defining
      optimal requirements of key minerals and vitamins for preventing damage to both
      nuclear and mitochondrial DNA. To date, our knowledge on optimal micronutrient
      levels for genomic stability is scanty and disorganised. However, there is
      already sufficient evidence to suggest that marginal deficiencies in folate,
      vitamin B12, niacin and zinc impact significantly on spontaneous chromosome
      damage rate. The recent data for folate and vitamin B12 in humans with respect to
      micronucleus formation in blood and epithelial cells provide compelling evidence
      of the important role of these micronutrients in maintenance of genome integrity
      and the need to revise current RDAs for these micronutrients based on
      minimisation of DNA damage. Appropriately designed in vitro studies and in vivo
      placebo controlled trials with dose responses using a complementary array of DNA
      damage biomarkers are required to define recommended dietary allowances for
      genomic stability. Furthermore these studies would have to be targeted to
      individuals with common genetic polymorphisms that alter the bioavailability of
      specific micronutrients and the affinity of specific key enzymes involved in DNA
      metabolism for their micronutrient co-factor. That there is a need for an
      international collaborative effort to establish RDAs for genomic stability is
      self-evident.

PMID- 12067573
TI  - DNA damage and antioxidants; fluctuations through the year in a central European
      population group.
AB  - Dietary antioxidant levels in the blood depend on intake of fruits and vegetables
      and therefore might be expected to show seasonal variation. A group of healthy
      male subjects in Bratislava, Slovakia gave blood samples each month for 1 year.
      Vitamin C, alpha- and gamma-tocopherol and several carotenoids were measured in
      plasma, and concentrations of essential metals zinc, copper and selenium in
      serum. Oxidative DNA damage was assessed in lymphocytes using the comet assay.
      Seasonal variations in antioxidant levels did not follow a common pattern. beta
      Cryptoxanthin was highest in the spring. Lycopene peaked in late summer.
      Lutein/zeaxanthin was higher in summer than in winter. The concentration of zinc
      in serum was higher in winter than in summer. DNA damage was lower in summer than
      in winter. Selenium as well as several antioxidants correlated negatively with
      indices of DNA damage, while zinc levels showed a positive correlation with DNA
      damage. These results provide some support for a link between consumption of
      antioxidants and protection against DNA oxidation.

PMID- 12067574
TI  - 2-Amino-1-methyl-6-(5-hydroxy-)phenylimidazo[4,5-b]pyridine (5-OH-PhIP), a
      biomarker for the genotoxic dose of the heterocyclic amine, 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP).
AB  - 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and
      carcinogenic heterocyclic amine formed during ordinary cooking. PhIP is
      metabolically activated by CYP P450 mediated N-hydroxylation followed by phase II
      esterification. The ultimate mutagenic metabolite reacts with DNA resulting in
      formation of adducts, and with proteins and other cellular constituents resulting
      in unstable products which are degraded to 5-hydroxy-PhIP. Rats were dosed orally
      with PhIP and urine and faeces were collected to 24, 48 and 72 h. Urine and
      faeces samples were hydrolysed with glucuronidase/sulfatase in order to release
      conjugated metabolites, followed by purification on C18 columns. The rats
      excreted 0.88% of the dose as 5-hydroxy-PhIP with the urine to 24 h and 0.04 and
      0.01% to 48 and 72 h, respectively. The amounts of 5-hydroxy-PhIP found in faeces
      were 0.03, 0.1 and 0% to 24, 48 and 72 h. Urinary excretion of 5-hydroxy-PhIP
      showed a linear dose-response relationship in rats dosed orally with PhIP. This
      shows that 5-hydroxy-PhIP is also formed in vivo and that 91% is excreted with
      the urine in 24 h, indicating the possible use of 5-hydroxy-PhIP as a urinary
      biomarker for the bioactive dose of PhIP. In a preliminary study, using molecular
      imprinted polymer a specific sorbent for purification, after enzymatic hydrolysis
      and purification on a C18 column, we have identified 5-OH-PhIP in a 24-h urine
      sample from a male volunteer who had ingested a fried beef. This indicates that
      urinary 5-OH-PhIP could be used as an easily obtainable marker for the genotoxic
      dose of PhIP in human biomonitoring studies.

PMID- 12067575
TI  - Biomarkers of exposure to heterocyclic amines: approaches to improve the exposure
      assessment.
AB  - Various methods of exposure assessment, such as questionnaires, sometimes
      combined with pictures of cooked meat, have been employed in investigations on
      the relationship between heterocyclic amines (HA) and health effects. However, as
      the content of heterocyclic amines vary greatly with cooking conditions, it is
      difficult to obtain an accurate estimate of the exposure. To improve the exposure
      assessment, the use of biomarkers has been investigated. The metabolism of 2
      amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) is well characterised. In humans, the major
      part of the dose is excreted in urine within 24-48 h following a meal. A few
      percent is excreted as parent compounds, whereas the major part is metabolites.
      Urinary level of parent HA reflects only recent exposure. However, the pattern of
      excreted metabolites might indicate the capacity to activate or detoxify HAs. The
      excretion of glucuronide conjugates of N-hydroxy-PhIP and N-hydroxy-MeIQx could
      be a marker for the N-hydroxylation capacity and the dose of the proximate
      metabolites. Recently, we proposed 5-OH-PhIP as a marker for the ultimate
      reactive metabolite of PhIP, since it is formed from this compound as a by
      product along with the formation of PhIP-DNA adducts. In a search for biomarkers
      reflecting exposure over some time, blood protein adducts with a longer lifespan
      have been investigated, and PhIP adducts of serum albumin and haemoglobin from
      meat-consuming humans were recently reported. Many compounds, like drugs,
      nicotine and narcotics, bind to melanin in hair and give information on exposure
      for longer time periods. In mice, PhIP is irreversibly incorporated in a dose
      dependent manner into hair, and in humans exposed to an ordinary diet, it was
      found to vary from <50 to 5000 pg PhIP/g hair. The incorporation is also
      dependent on the content of eumelanin. The use of PhIP in hair as a biomarker of
      exposure is promising, but needs validation, using other methods of exposure
      assessment.

PMID- 12067576
TI  - Role of metabolic polymorphisms NAT2 and CYP1A2 on urinary mutagenicity after a
      pan-fried hamburger meal.
AB  - In this work the phenotyping approach was used to study the influence of
      metabolic polymorphisms NAT2 and CYP1A2 on S9-mediated urinary mutagenicity,
      detected with Salmonella strain YG1024, in 50 subjects after a meal of pan-fried
      hamburgers. All 50 post-meal samples, but not pre-meal ones, were clearly
      mutagenic (number of urine samples able to double number of spontaneous
      revertants was 50 to 0, respectively). CYP1A2 positively influences urinary
      mutagenicity: a rise in CYP1A2 activity increases levels of post-meal urinary
      mutagens (1.16+/-0.91 vs 1.72+/-1.19 7-h minimum mutagenic doses (MMDs)/intake),
      especially in NAT2 slow acetylators (2.18+/-1.33 vs 0.90+/-0.54 7-h MMDs/intake,
      Mann-Whitney U-test, P<0.05). NAT2 rapid acetylators exert lower post-meal
      urinary mutagenicity than slow ones (1.41+/-1.02 vs 1.77+/-2.45 7-h MMDs/intake)
      and even more if the latter are extensive CYP1A2 metabolizers (1.41+/-1.02 vs
      2.18+/-1.33 7-h MMDs/intake), but the difference did not reach statistical
      significance. In conclusion, this study indicates that CYP1A2 and NAT2 activities
      influence the presence of urinary mutagens after a meal of pan-fried hamburger
      (rich in HHAs) and consequently their potential genotoxic risk.

PMID- 12067578
TI  - Cafestol and kahweol, two coffee specific diterpenes with anticarcinogenic
      activity.
AB  - Epidemiological studies have found an inverse association between coffee
      consumption and the risk of certain types of cancers such as colorectal cancers.
      Animal data support such a chemopreventive effect of coffee. Substantial research
      has been devoted to the identification of coffee components that may be
      responsible for these beneficial effects. In animal models and cell culture
      systems, the coffee diterpenes cafestol and kahweol (C+K) were shown to produce a
      broad range of biochemical effects resulting in a reduction of the genotoxicity
      of several carcinogens including 7,12-dimethylbenz[a]anthracene (DMBA), aflatoxin
      B(1) (AFB(1)), benzo[a]pyrene (B[a]P) and 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP). Different mechanisms appear to be involved in these
      chemoprotective effects: an induction of conjugating enzymes (e.g. glutathione S
      transferases, glucuronosyl S-transferases), an increased expression of proteins
      involved in cellular antioxidant defense (e.g. gamma-glutamyl cysteine synthetase
      and heme oxygenase-1) and an inhibition of the expression and/or activity of
      cytochromes P450 involved in carcinogen activation (e.g. CYP2C11, CYP3A2). In
      animal models, the C+K-mediated induction of conjugating and antioxidant enzymes
      has been observed in hepatic, intestinal and kidney tissues. In the small
      intestine, these inductions were shown to be mediated by Nrf2-dependent
      transcriptional activation. In vitro investigations obtained in cell cultures of
      human origin indicate that the effects and mechanisms observed in animal test
      systems with C+K are likely to be of relevance for humans. In human liver
      epithelial cell lines transfected to express AFB(1)-activating P450s, C+K
      treatment resulted in a reduction of AFB(1)-DNA binding. This protection was
      correlated with an induction of GST-mu, an enzyme known to be involved in AFB(1)
      detoxification. In addition, C+K was found to inhibit P450 2B6, one of the human
      enzymes responsible for AFB(1) activation. Altogether, the data on the biological
      effects of C+K provide a plausible hypothesis to explain some of the
      anticarcinogenic effects of coffee observed in human epidemiological studies and
      in animal experiments.

PMID- 12067577
TI  - Mechanisms of chronic disease causation by nutritional factors and tobacco
      products and their prevention by tea polyphenols.
AB  - The beverage tea, from the top leaves of the plant Camellia sinensis is one of
      the most widely used beverages in the world, second only to water. Black and
      green tea have mostly similar actions. The active components are polyphenols,
      mainly epigallocatechin gallate in green tea, and the tea leaf polyphenol oxidase
      mediated oxidation to oolong and black tea, yielding other polyphenols,
      theaflavin and thearubigins. There is 40-50 mg caffeine in a 160-ml cup of tea.
      The chemopreventive effects of tea depend on: (1) its action as an antioxidant;
      (2) the specific induction of detoxifying enzymes; (3) its molecular regulatory
      functions on cellular growth, development and apoptosis; and (4) a selective
      improvement in the function of the intestinal bacterial flora. The oxidation of
      LDL cholesterol, associated with a risk for atherosclerosis and heart disease, is
      inhibited by tea. Many of cancers are caused by lifestyle elements. One is
      cigarette and tobacco use, leading to cancer in the oral cavity, esophagus and
      lung, inhibited by tea. Mice administered a tobacco nitrosamine, 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), developed significantly fewer
      lung tumors than controls when given green tea or its major polyphenol,
      epigallocatechin gallate (EGCG). Tea suppressed the formation of 8
      hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, in the lung DNA
      of mice given NNK. Gastric cancer, caused by a combination of Helicobacter pylori
      and salted foods, is lower in tea drinkers. Western nutritionally-linked cancers
      of the breast, colon, prostate and pancreas can be inhibited by tea. The
      formation of genotoxic carcinogens for these target organs during the cooking of
      meats, heterocyclic amines, and their effects were decreased by tea. Tea
      inhibited the formation of reactive oxygen species and radicals and induced
      cytochromes P450 1A1, 1A2 and 2B1, and glucuronosyl transferase. The higher
      formation of glucuronides represents an important mechanism in detoxification.
      The developmental aspects and growth of cancers through promotion are decreased
      by tea. The regular use of a widely available, tasty, inexpensive beverage, tea,
      has displayed valuable preventive properties in chronic human diseases.

PMID- 12067579
TI  - Pseudouridine, an antimutagenic substance in beer towards N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG).
AB  - Previously we reported that beer is antimutagenic against several food-derived
      mutagens including heterocyclic amines. We describe here the isolation and
      identification of pseudouridine from beer as an antimutagenic substance against N
      methyl-N'-nitro-N-nitrosoguanidine (MNNG). All of the 17 samples of beer tested
      showed inhibition of the MNNG mutagenicity in Salmonella. Extensive fractionation
      through chromatography of the active components from a freeze-dried beer sample
      gave six antimutagenic fractions. One contained pseudouridine, as characterized
      by the UV spectra, nuclear magnetic resonance, and co-chromatography in HPLC.
      Pure pseudouridine inhibited the mutagenicity of MNNG in a dose-dependent manner.
      The amount of pseudouridine in the beer sample, estimated at about 0.4 mg/100 ml
      beer, can account for 3% of the total antimutagenicity of beer. Thus, the major
      active components in beer remain to be identified. The role of pseudouridine in
      inhibiting the mutagenicity of MNNG is to be studied further. Among analogs of
      pseudouridine, spongouridine, but not uridine, was antimutagenic against MNNG.
      The bacterial mutagenicity of another methylating agent N-methyl-N-nitrosourea
      was also inhibited by pseudouridine. Pseudouridine is the first example among
      nucleosides to be shown to possess an antimutagenic property.

PMID- 12067580
TI  - Anticarcinogenic effects of diet-related apoptosis in the colorectal mucosa.
AB  - The crypt is the fundamental unit of epithelial proliferation in the intestinal
      mucosa. The progeny of the pluripotent stem cells located near the base of the
      crypt migrate towards the crypt orifice, divide once or twice more, and then
      undergo differentiation, senescence and exfoliation. Programmed cell death
      (apoptosis) also occurs deep in the proliferative zone. Various lines of evidence
      suggest that apoptosis provides a protective mechanism against neoplasia by
      removing genetically damaged stem cells from the epithelium before they can
      undergo clonal expansion. Several different classes of food constituents,
      including certain polyunsaturated fatty acids, the short-chain fatty acid
      butyrate, and some phytochemicals including flavonoids and glucosinolates
      breakdown products, can modulate both cellular proliferation and programmed
      death. Each of these food components has also been shown to suppress the
      emergence of aberrant crypt foci in animal models of carcinogenesis. Further
      mechanistic and clinical studies are required to establish whether such dietary
      effects can be exploited to achieve preventive or therapeutic effects in humans.

PMID- 12067581
TI  - Interference by toxic metal ions with zinc-dependent proteins involved in
      maintaining genomic stability.
AB  - Metal ions are essential components of biological systems; nevertheless, even
      essential elements may have toxic or carcinogenic properties. Thus, besides
      As(III) and Cd(II), also Ni(II) and Co(II) have been shown previously to disturb
      different types of DNA repair systems at low, non-cytotoxic concentrations. Since
      some metals exert high affinities for SH groups, we investigated whether zinc
      finger structures in DNA-binding motifs of DNA repair proteins are potential
      targets for toxic metal ions. The bacterial formamidopyrimidine-DNA glycosylase
      (Fpg protein) involved in base excision repair was inhibited by Cd(II), Cu(II)
      and Hg(II) with increasing efficiencies, whereas Co(II), As(III), Pb(II) and
      Ni(II) had no effect. Furthermore, Cd(II) still disturbed enzyme function when
      bound to metallothionein. Strong inhibition was also observed in the presence of
      phenylselenyl chloride, followed by selenocystine, while selenomethionine was not
      inhibitory. Regarding the mammalian XPA protein involved in the recognition of
      DNA lesions during nucleotide excision repair, its DNA-binding capacity was
      diminished by Cd(II), Cu(II), Ni(II) and Co(II), while Hg(II), Pb(II) and As(III)
      were ineffective. Finally, the H(2)O(2)-induced activation of the poly(ADP
      ribose)polymerase (PARP) involved in DNA strand break detection and apoptosis was
      greatly reduced by Cd(II), Co(II), Ni(II) and As(III). Similarly, the disruption
      of correct p53 folding and DNA binding by Cd(II), Ni(II) and Co(II) has been
      shown by other authors. Therefore, zinc-dependent proteins involved in DNA repair
      and cell-cycle control may represent sensitive targets for some toxic metals such
      as Cd(II), Ni(II), Co(II) and Cu(II), as well as for some selenium compounds.
      Relevant mechanisms of inhibition appear to be the displacement of zinc by other
      transition metals as well as redox reactions leading to thiol/disulfide
      interchange.

PMID- 12067582
TI  - Risk assessment of dioxin contamination in human food.
AB  - Dioxins are highly toxic by-products of incineration processes and of production
      of chloro-organic chemicals. Accidental poisonings have occurred repeatedly. The
      main human exposure is via the dietary route. Species comparisons of toxic
      effects on the basis of ingested doses are not possible because of the highly
      differing toxicokinetics between humans and experimental animals. On the basis of
      internal doses or body burdens acute toxic and tumorigenic responses are observed
      at similar levels in humans and rats. PCB/PCDD/F contamination at levels which
      have been reported of marketed chicken meat and eggs in 1999 in Belgium may have
      increased body burdens by approximately 10%. However, it is estimated that a
      several hundred-fold higher uptake would be necessary to reach body burdens
      leading to overt toxicity in normal human subjects.

PMID- 12067583
TI  - Vitamin D receptor activity and prevention of colonic hyperproliferation and
      oxidative stress.
AB  - Unimpaired vitamin D action has been implicated in human cancer prevention. We
      have previously demonstrated the effectiveness of 1 alpha-dihydroxyvitamin D3
      (1,25-D3) to reduce proliferation and increase differentiation in human colon
      cancer cells. The aim of this study was to investigate, on the one hand,
      expression of the vitamin D receptor (VDR) and of 25-hydroxyvitamin D(3)-1 alpha
      hydroxylase (1 alpha-hydroxylase) in human normal and malignant colonic tissue
      and, on the other hand, to determine consequences of reduced or lacking VDR
      action in a VDR knockout mouse model. In low-grade malignancies of the human
      colon we found increased VDR and 1 alpha-hydroxylase mRNA expression. However, in
      late-stage high-grade tumors the vitamin D system is severely compromised. In the
      mouse colon we found an inverse relationship between VDR levels and proliferation
      in colon descendens, a tissue known to be specifically affected by nutrients
      during carcinogenesis. Expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a
      marker of oxidative DNA damage, was significantly augmented with complete loss of
      VDR. These data suggest that genomic 1,25-D(3) action is necessary to protect
      against nutrition-linked hyperproliferation and oxidative DNA damage.

PMID- 12067584
TI  - Problems associated with the determination of heterocyclic amines in cooked foods
      and human exposure.
AB  - Epidemiological studies have shown diet to be an important factor in the global
      variation of human cancer rates. The presence of mutagenic/carcinogenic
      heterocyclic aromatic amines (HAs) in cooked foods has attracted a great deal of
      interest for more than 20 years. Accurate assessment of the human exposure to HAs
      requires food questionnaires that address cooking methods and reliable methods
      for the analysis of HAs in cooked foods, and of biomarkers of exposure. The
      complex food matrix, the low amounts of HAs present (ng/g), and the need for
      several isolation steps make accurate quantification difficult. Food composition,
      for example the concentrations and relative amounts of naturally occurring
      precursors, such as creatine, free amino acids and sugars and also the presence
      of enhancing or inhibiting compounds are known to greatly influence the formation
      of HAs. Cooking temperature and time are other important factors that affect the
      yield of HAs. One of the most abundant HAs, PhIP (2-amino-1-methyl-6-phenyl
      imidazo[4,5-b]pyridine), is found typically in amounts up to around 35 ng/g, but
      there are some reports on much higher levels of PhIP. The levels of other HAs
      such as MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and IFP (2-amino
      1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine) generally range from not
      detectable up to 10 ng/g, and AalphaC (2-amino-9H-pyrido[2,3-b]indole) up to 20
      ng/g. Among the factors that influence human exposure to HAs are the type of
      food, cooking method, portion size and intake frequency. The estimated daily
      intake of HAs in different studies ranges from 0 to around 15 microg per person
      per day.

PMID- 12067585
TI  - Screening for heterocyclic amines in chicken cooked in various ways.
AB  - Chicken cooked under well-controlled conditions and commercial chicken products
      were screened for heterocyclic amines (HAs). Chicken samples were boiled, deep
      fried, pan-fried, oven-roasted, cooked in an unglazed clay pot or in a roasting
      bag in the oven, and oven broiled. 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline
      (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 1-methyl-9H-pyrido[3,4-b]indole
      (harman) and 9H-pyrido[3,4-b]indole (norharman) were identified in several
      samples. Chicken cooked at low temperatures contained low amounts of HAs. In pan
      fried chicken breasts, MeIQx was detected in amounts below 2 ng/g, 4,8-DiMeIQx
      below 0.6 ng/g, and PhIP in amounts up to 38 ng/g. Harman and norharman were
      detected in almost all samples (below 15 ng/g). In skin from a commercially
      barbecued chicken, MeIQx, 4,8-DiMeIQx and PhIP were detected, while only traces
      of MeIQx were detected in the meat. MeIQx was detected in a commercial chicken
      flavour, 0.1 ng/ml. No HAs were detected in pan-fried chicken liver. The results
      show that the content of HAs in chicken cooked in various ways is low if prepared
      at low temperatures, and increases with increasing cooking temperature. PhIP
      formation seems to start accelerating at cooking temperatures around or above 200
      degrees C. Colour development increases with cooking temperature, but no
      correlation with HA content was observed.

PMID- 12067586
TI  - Heterocyclic amines in poultry products: a literature review.
AB  - Health risks associated with heterocyclic amines in cooked foods have been
      discussed and analysed since the presence of these food mutagens was first
      detected. Intake, metabolism, carcinogenicity and epidemiology are important
      parameters in the risk assessment of heterocyclic amines. It is very difficult to
      determine the human intake of heterocyclic amines, as the content in cooked meat
      is highly dependent on the type of meat and how it has been prepared. This review
      summarises data on estimates of the content of heterocyclic amines in heat
      treated poultry products.

PMID- 12067587
TI  - Nitrosation of dietary myosmine as risk factor of human cancer.
AB  - The tobacco alkaloid myosmine was detected in nut and nut products [J. Agric.
      Food Chem. 46 (1998) 2703]. Upon nitrosation, myosmine yields 4-hydroxy-1-(3
      pyridyl)-1-butanone (HPB) and N-nitrosonornicotine (NNN) [J. Agric. Food Chem. 48
      (2001) 392]. NNN is a strong oesophageal carcinogen in rats. Metabolic activation
      of NNN leads to formation of DNA and protein adducts which release HPB upon
      hydrolysis. In the present study the time, pH and dose-dependent nitrosation of
      myosmine and its covalent binding to DNA was investigated. [5-(3)H]myosmine was
      incubated with nitrite for 1-24 h in buffer solutions adjusted to pH 1-6. At pH 2
      4 myosmine was easily nitrosated and gave rise to two major products, HPB and
      NNN, and five minor not yet identified products. Maximal formation was achieved
      for HPB at pH 2 after 8 h (72% of total radioactivity) and for NNN at pH 3 after
      8 h (16%). For DNA binding studies labeled myosmine was incubated under
      nitrosation conditions with calf thymus DNA. Within 3 h up to 0.1% of the
      radioactivity was covalently bound to DNA. Endogenous nitrosation of myosmine,
      present in nuts and other dietary components could constitute a significant risk
      factor for tumours in the upper intestinal tract such as oesophageal
      adenocarcinoma, which are unrelated to tobacco smoking and alcohol abuse.

PMID- 12067588
TI  - Regulation of lifespan by histone deacetylase.
AB  - Aging is a universal biological phenomenon in eukaryotes, but why and how we age
      still remain mysterious. It would be of great biological interest and practical
      importance if we could uncover the molecular mechanism of aging, and find a way
      to delay the aging process while maintaining physical and mental strengths of
      youth. Histone deacetylases (HDACs) such as SIR2 and RPD3 are known to be
      involved in the extension of lifespan in yeast and Caenorhabditis elegans. An
      inhibitor of HDACs, phenylbutyrate, also can significantly increase the lifespan
      of Drosophila, without diminution of locomotor vigor, resistance to stress, or
      reproductive ability. Treatment for a limited period, either early or late in
      adult life, is also effective. Alteration in the pattern of gene expression,
      including induction or repression of numerous genes involved in longevity by
      changing the level and the pattern of histone acetylation may be an important
      factor in determining the longevity of animals.

PMID- 12067589
TI  - Amyloid peptide enhances nail rusting: novel insight into mechanisms of aging and
      Alzheimer's disease.
AB  - Oxidative stress is believed to play a major role in the dysfunction and
      degeneration of neurons that occurs in Alzheimer's disease (AD). Amyloid beta
      peptide forms insoluble aggregates in the brains of AD patients and it has been
      shown that the neurotoxic actions of amyloid beta-peptide involve membrane lipid
      peroxidation. However, it is not known how amyloid beta-peptide induces oxidative
      stress. Here we describe a simple experiment that we performed 6 years ago that
      demonstrates that amyloid beta-peptide is itself a source of oxyradicals. The
      weights of iron nails were recorded and the nails were then incubated in one of
      three different solutions: water (control), 1mM amyloid beta-peptide (1-40) in
      water, and 1mM bovine serum albumin in water. After 1 month of incubation the
      nails were then removed, allowed to dry, and then their weights determined. The
      weights of all the nails decreased, but the amount of weight decrease in the
      nails that had been incubated in the presence of amyloid beta-peptide was
      approximately twice that of the nails incubated in the control solutions. These
      data provide direct evidence that amyloid beta-peptide generates, or facilitates
      the production of, oxyradicals thereby enhancing metal oxidation.

PMID- 12067590
TI  - Molecular mechanisms of age-related hearing loss.
AB  - Age-related hearing loss, known as presbyacusis, is characterized by the
      progressive deterioration of auditory sensitivity associated with aging and is
      the most common cause of adult auditory deficiency in the United States.
      Presbyacusis is defined as a progressive, bilateral, high-frequency hearing loss
      that is manifested on audiometric assessment by a moderately sloping pure tone
      audiogram. This condition affects approximately 23% of the population between 65
      and 75 years of age and 40% of the population older than 75 years of age. In
      1980, it was estimated that 11% of the population was 76 years or older and this
      number is expected to nearly double by the year 2030 [, Otolaryngol. Head Neck
      Surg. 100, 262]. When coupled with the fact that the population over 65 years of
      age is experiencing the most rapid progression of hearing loss, the potential
      socioeconomic ramifications are staggering. Interestingly, presbyacusis varies in
      its frequency across differing societies. This discrepancy has been attributed to
      many factors such as genetics, diet, socioeconomic factors, and environmental
      variables [, Otolaryngol. Head Neck Surg. 100, 266;. Scand. Audiol. 26 (1997)
      133]. The purpose of this discussion is to illuminate the various molecular
      mechanisms underlying this age-related hearing loss and to offer insights into
      potential ways to mitigate the effects of aging on hearing impairment.

PMID- 12067591
TI  - Apolipoproteins and aging: emerging mechanisms.
AB  - One of the goals of modern medicine is to foster successful aging. In order to
      age successfully, one must accomplish two things: first, survive; and second,
      survive with good health and a sharp mind. In this discussion of apolipoproteins
      and aging, the focus will be on apolipoprotein E (apoE), a protein with three
      common isoforms, which has a large impact on longevity and successful aging. One
      variant of apoE (E4) is associated with increased risk for heart disease, stroke
      and Alzheimer's disease (AD). In addition, some of the potential mechanisms for
      the observed effects of apoE on aging will be discussed.

PMID- 12067592
TI  - Impacts of transcriptional regulation on aging and senescence.
AB  - The genetic makeup of the organism appears to dictate the species-specific rate
      of aging and the maximum life-span potential. The genotype is converted to
      phenotype through transcriptional and translational regulation. A group of gene
      regulatory proteins (transcription factors) play critical roles in controlling
      the rates of transcription of specific genes by directly interacting with
      regulatory sequences at gene promoters. Here, we review the basic mechanism of
      transcriptional control and the role of a number of transcription factors whose
      level and/or activity alter with age. Among these age-dependent transcription
      factors, many are involved in the regulation of stress and inflammatory responses
      and are subjected to functional alterations by reactive oxygen species (ROSs). A
      progressive rise of oxidative stress, impaired ability to cope with stressful
      stimuli and prolongation of the inflammatory response are some of the hallmarks
      of the senescent phenotype. Results published to date are supportive of the
      concept that a species-specific program of the temporal regulation of genes with
      additional modulation by a number of epigenetic factors, mediates the age
      dependent deterioration of physiological functions and development of the
      senescent phenotype.

PMID- 12067593
TI  - Photoreceptor degeneration and dysfunction in aging and age-related maculopathy.
AB  - The relative rate of rod and cone degeneration is a fundamental characteristic of
      any disorder affecting photoreceptors, including aging and age-related
      maculopathy (ARM). The human macula consists of a small cone-dominated fovea
      surrounded by a rod-dominated parafovea. In aging and early ARM, rods degenerate
      before cones, a decline in scotopic (rod-mediated) sensitivity is more prominent
      than a decline in photopic (cone-mediated) sensitivity, and the time course of
      dark adaptation of rods slows dramatically. The topography of rod dysfunction and
      loss in early ARM matches the location of pathology in the retinal pigment
      epithelium (RPE)/Bruch's membrane complex visible in the ocular fundus. Rod
      dysfunction and loss in aging and ARM may be due to retinoid deficiency at the
      level of the photoreceptors cause by impaired retinoid translocation across the
      RPE/Bruch's membrane complex, a hypothesis deserving of further investigation.

PMID- 12067594
TI  - Endogenous oxidative stress: relationship to aging, longevity and caloric
      restriction.
AB  - Available studies are consistent with the possibility that oxygen radicals
      endogenously produced by mitochondria are causally involved in the determination
      of the rate of aging in homeothermic vertebrates. Oxidative damage to tissue
      macromolecules seems to increase during aging. The rate of mitochondrial oxygen
      radical generation of post-mitotic tissues is negatively correlated with animal
      longevity. In agreement with this, long-lived animals show lower levels of
      oxidative damage in their mitochondrial DNA (mtDNA) than short-lived ones,
      whereas this does not occur in nuclear DNA (nDNA). Caloric restriction, which
      decreases the rate of aging, also decreases mitochondrial oxygen radical
      generation and oxidative damage to mitochondrial DNA. This decrease in free
      radical generation occurs in complex I and is due to a decrease in the degree of
      electronic reduction of the complex I free radical generator, similarly to what
      has been described in various cases in long-lived animals. These results suggest
      that similar mechanisms have been used to extend longevity through decreases in
      oxidative stress in caloric restriction and during the evolution of species with
      different longevities.

PMID- 12067595
TI  - Premature ovarian failure (POF): discordance between somatic and reproductive
      aging.
AB  - Premature ovarian failure (POF) is a unique example of isolated organ senescence,
      with a population prevalence of approximately 1%. Though the phenotypic
      expression of POF is similar to that of age-appropriate natural menopause, the
      underlying pathophysiological mechanisms are diverse and not entirely clear. The
      impact of POF on the patient is profound, with myriad ramifications, ranging from
      psychological devastation to multi-system implications of estrogen deprivation
      and its sequelae. The hastening of degenerative changes noted in these patients
      however, are not entirely ameliorated with estrogen replacement and POF may
      indeed represent an acceleration of the aging process.

PMID- 12067596
TI  - Genes, mitochondria and aging in filamentous fungi.
AB  - Fungi are eukaryotic microorganisms studied in various areas of general and
      applied biology. A few species were among the first systems in which specific
      aspects of aging were addressed experimentally. Various factors, both
      environmental and genetic, were found to affect lifespan and aging. Mitochondrial
      pathways play a paramount role. Since mitochondria are semiautonomous organelles
      and depend on both nuclear as well as mitochondrial genes, mitochondrial-nuclear
      interactions are of major relevance. As a main generator of reactive oxygen
      species (ROS), mitochondria are prone to molecular damage. However, cells can
      cope with the negative effects of ROS utilizing different scavenging systems and,
      once defects became manifested, by repair of damaged molecules. Both, lowering
      ROS generation and increasing mitochondrial "caretaker" systems bear great
      potential to interfere with natural aging processes.

PMID- 12067597
TI  - Replicative enzymes and ageing: importance of DNA polymerase alpha function to
      the events of cellular ageing.
AB  - A hallmark of cellular ageing is the failure of senescing cells to initiate DNA
      synthesis and transition from G1 into S phase of the cell cycle. This transition
      is normally dependent on or concomitant with expression of a set of genes
      specifying cellular proteins, some of which directly participate in DNA
      replication. Deregulation of this gene expression may play a pivotal role in the
      ageing process. The number of known enzymes and co-factors required to maintain
      integrity of the genome during eukaryotic DNA replication has increased
      significantly in the past few years, and includes proteins essential for DNA
      replication and repair, as well as for cell cycle regulation. In eukaryotic
      cells, ranging from yeast to man, a replicative enzyme essential for initiation
      of transcription is DNA polymerase alpha (pol alpha), the activity of which is
      coordinately regulated with the initiation of DNA synthesis. DNA pol alpha, by
      means of its primase subunit, has the unique ability to initiate de novo DNA
      synthesis, and as a consequence, is required for the initiation of continuous
      (leading-strand) DNA synthesis at an origin of replication, as well as for
      initiation of discontinuous (lagging-strand) DNA synthesis. The dual role of the
      pol alpha-primase complex makes it a potential interactant with the regulatory
      mechanisms controlling entry into S phase. The purpose of this review is to
      address the regulation and/or modulation of DNA pol alpha during ageing that may
      play a key role in the cascade of events which ultimately leads to the failure of
      old cells to enter or complete S phase of the cell cycle.

PMID- 12067598
TI  - Viewing molecular mechanisms of ageing through a lens.
AB  - Many late-life diseases are conformational diseases in tissues where there are
      unfolded or misfolded proteins which can form aggregates. These diseases have
      other common features in their aetiology. Cataract is one such disease and post
      translational modifications of proteins in the lens during cataract formation are
      described as a possible guide to the changes in other age-related conditions.
      Delineation of common pathways in these diseases could lead to common treatment
      regimes, and in this respect, there are promising results for aspirin-like drugs
      in Alzheimer's disease, cataract, myocardial infarction, stroke and various
      cancers.

PMID- 12067599
TI  - Aging is a deprivation syndrome driven by a germ-soma conflict.
AB  - Evolution through natural selection can be described as driven by a perpetual
      conflict of individuals competing for limited resources. Recently, I postulated
      that the shortage of resources godfathered the evolutionary achievements of the
      differentiation-apoptosis programming [Rev. Neurosci. 12 (2001) 217]. Unicellular
      deprivation-induced differentiation into germ cell-like spores can be regarded as
      the archaic reproduction events which were fueled by the remains of the
      fratricided cells of the apoptotic fruiting body. Evidence has been accumulated
      suggesting that conserved through the ages as the evolutionary legacy of the germ
      soma conflict, the somatic loss of immortality during the ontogenetic segregation
      of primordial germ cells recapitulates the archaic fate of the fruiting body. In
      this heritage, somatic death is a germ cell-triggered event and has been
      established as evolutionary-fixed default state following asymmetric reproduction
      in a world of finite resources. Aging, on the other hand, is the stress
      resistance-dependent phenotype of the somatic resilience that counteracts the
      germ cell-inflicted death pathway. Thus, aging is a survival response and, in
      contrast to current beliefs, is antagonistically linked to death that is not
      imposed by group selection but enforced upon the soma by the selfish genes of the
      "enemy within". Environmental conditions shape the trade-off solutions as
      compromise between the conflicting germ-soma interests. Mechanistically, the
      neuroendocrine system, particularly those components that control energy balance,
      reproduction and stress responses, orchestrate these events. The reproductive
      phase is a self-limited process that moulds onset and progress of senescence with
      germ cell-dependent factors, e.g. gonadal hormones. These degenerate the
      regulatory pacemakers of the pineal-hypothalamic-pituitary network and its
      peripheral, e.g. thymic, gonadal and adrenal targets thereby eroding the trophic
      milieu. The ensuing cellular metabolic stress engenders adaptive adjustments of
      the glucose-fatty acid cycle, responses that are adequate and thus fitness
      boosting under fuel shortage (e.g. during caloric restriction) but become
      detrimental under fuel abundance. In a Janus-faced capacity, the cellular stress
      response apparatus expresses both tolerogenic and mutagenic features of the
      social and asocial deprivation responses [Rev. Neurosci. 12 (2001) 217]. Mediated
      by the derangement of the energy-Ca(2+)-redox homeostatic triangle, a mosaic of
      dedifferentiation/apoptosis and mutagenic responses actuates the gradual
      exhaustion of functional reserves and eventually results in a multitude of aging
      related diseases. This scenario reconciles programmed and stochastic features of
      aging and resolves the major inconsistencies of current theories by linking
      ultimate and proximate causes of aging. Reproduction, differentiation, apoptosis,
      stress response and metabolism are merged into a coherent regulatory network that
      stages aging as a naturally selected, germ cell-triggered and reproductive phase
      modulated deprivation response.

PMID- 12067600
TI  - Neurohypophyseal peptides in aging and Alzheimer's disease.
AB  - The neurohypophyseal hormones arginine-vasopressin (AVP) and oxytocin (OT) are
      produced in the neurons of the hypothalamic supraoptic (SON) and paraventricular
      (PVN) nucleus and in the much smaller cells of the suprachiasmatic (SCN) nucleus.
      The SON is the main source of plasma AVP. Part of the AVP and OT neurons of the
      PVN join the hypothalamo-neurohypophyseal tract, whereas others send projections
      to the median eminence or various brain areas, where AVP and OT are involved in a
      number of central functions as neurotransmitters/neuromodulators. AVP and OT from
      the PVN can also regulate via the autonomous innervation endocrine glands and fat
      tissue. OT is produced for a major part in the PVN but some OT neurons are
      present in the SON. Moreover, both AVP and OT containing neurons are observed in
      the "accessory nuclei", i.e. islands situated between the SON and PVN. The SCN is
      the biological clock, and the number of AVP expressing neurons in the SCN shows
      both diurnal and seasonal rhythms. In addition to these hypothalamic areas, AVP
      and OT may be found to a lesser extent in some other brain areas, such as the bed
      nucleus of the stria terminalis, diagonal band of Broca, nucleus basalis of
      Meynert, lateral septal nucleus, globus pallidus and the anterior amygdaloid
      nucleus, as well as in the peripheral tissues. The AVP and OT containing neurons
      should not be considered as one system. Prominent functional differences exist
      between the different nuclei. The heterogeneity also becomes clear from the
      marked differences in the neurohypophyseal peptides containing neurons of the
      SON, PVN and SCN during aging, and in the most prevalent age-related
      neurodegenerative diseases, i.e. Alzheimer's disease (AD). For those reasons, we
      will discuss the SON, PVN and SCN separately.

PMID- 12067601
TI  - Senescence, sleep, and circadian rhythms.
AB  - The goal of this review article is to summarize our knowledge and understanding
      of the overlapping (interdisciplinary) areas of senescence, sleep, and circadian
      rhythms. Our overview comprehensively (and visually wherever possible),
      emphasizes the organizational, dynamic, and plastic nature of both sleep and
      circadian timing system (CTS) during senescent processes in animals and in
      humans. In this review, we focus on the studies that deal with sleep and
      circadian rhythms in aged animals and how these studies have closely correlated
      to and advanced our understanding of similar processes in ageing humans. Our
      comprehensive summary of various aspects of the existing research on animal and
      human ageing, both normal and pathological, presented in this review underscores
      the invaluable advantage of close collaboration between clinicians and basic
      research scientists and the future challenges inherent in this collaboration.
      First, our review addresses the common age-related changes that occur in sleep
      and temporal organization of both animals and humans. Second, we examine the
      specific modifications that often accompany sleep and CTS during aging. Third, we
      discuss the clinical epidemiology of sleep dysfunctions during ageing and their
      current clinical management, both pharmacological and non-pharmacological.
      Finally, we predict the possible future promises for complementary and
      alternative medicine (CAM) that pave the way to the emergence of a "Holistic
      Sleep Medicine" approach to the treatment of sleep disorders in the ageing
      population. Further studies will provide additional valuable insights into the
      understanding of both sleep and circadian rhythms during senescence.

PMID- 12067602
TI  - Molecular diagnostics: the best is yet to come.

PMID- 12067603
TI  - Modern molecular cytogenetic techniques in genetic diagnostics.
AB  - During the past decade, fluorescence in situ hybridization (FISH) has become an
      important complementing application in genetic diagnostics. The use of variable
      FISH techniques enhances the thorough interpretation of numerical and complex
      chromosome aberrations, bridging the gap between conventional chromosome banding
      analysis and molecular genetic DNA studies. This review gives a brief overview of
      the different molecular cytogenetic FISH techniques and applications currently
      used in routine genetic diagnostics and focus on their advantages and
      limitations.

PMID- 12067604
TI  - High-throughput protein arrays: prospects for molecular diagnostics.
AB  - High-throughput protein arrays allow the miniaturized and parallel analysis of
      large numbers of diagnostic markers in complex samples. Using automated colony
      picking and gridding, cDNA or antibody libraries can be expressed and screened as
      clone arrays. Protein microarrays are constructed from recombinantly expressed,
      purified, and yet functional proteins, entailing a range of optimized expression
      systems. Antibody microarrays are becoming a robust format for expression
      profiling of whole genomes. Alternative systems, such as aptamer, PROfusion, nano
      and microfluidic arrays are all at proof-of-concept stage. Differential protein
      profiles have been used as molecular diagnostics for cancer and autoimmune
      diseases and might ultimately be applied to screening of high-risk and general
      populations.

PMID- 12067605
TI  - Challenges of single-cell diagnostics: analysis of gene expression.
AB  - Analysis of single-cell gene expression promises a more precise understanding of
      human disease pathogenesis and important diagnostic applications. Here, we review
      the rationale for the study of gene expression at the single-cell level,
      practical methods to isolate homogeneous or single-cell samples, and current
      approaches to the analysis of single-cell gene expression. Finally, we highlight
      applications of laser microdissection-based gene expression analysis to the study
      of human disease and clinical diagnosis.

PMID- 12067606
TI  - Quantification using real-time PCR technology: applications and limitations.
AB  - The introduction of real-time PCR technology has significantly improved and
      simplified the quantification of nucleic acids, and this technology has become an
      invaluable tool for many scientists working in different disciplines. Especially
      in the field of molecular diagnostics, real-time PCR-based assays have gained
      favour in the recent past. However, the wide use of real-time PCR methods has
      also highlighted some of the critical points and limitations of these assays.
      These aspects must be considered to increase the reliability of the obtained
      data.

PMID- 12067610
TI  - Molecular diagnostics: hurdles for clinical implementation.
AB  - In the coming years, molecular diagnostics will continue to be of critical
      importance to public health worldwide. It will facilitate the detection and
      characterization of disease, as well as monitoring of the drug response, and will
      assist in the identification of genetic modifiers and disease susceptibility. A
      wide range of molecular-based tests is available to assess DNA variation and
      changes in gene expression. However, there are major hurdles to overcome before
      the implementation of these tests in clinical laboratories, such as which test to
      employ, the choice of technology and equipment, and issues such as cost
      effectiveness, accuracy, reproducibility, personnel training, reimbursement by
      third-party payers and intellectual property. At present, PCR-based testing
      predominates; however, alternative technologies aimed at reducing genome
      complexity without PCR are anticipated to gain momentum in the coming years.
      Furthermore, development of integrated chip devices ("lab-on-a-chip") should
      allow point-of-care testing and facilitate genetic readouts from single cells and
      molecules. Together with proteomic-based testing, these advances will improve
      molecular diagnostic testing and will present additional challenges for
      implementing such testing in health care settings.

PMID- 12067611
TI  - One gene and one outcome? No way.
AB  - The world of molecular diagnostics is undergoing major change because of both
      technical advances and the availability of rapidly expanding genetic databases
      generated by the study of human genomics. These resources comprise an
      extraordinary opportunity to decipher the biological importance of genetic
      aberrations, and link our understanding with clinical utility. The challenge lies
      in sorting through the information and developing effective strategies to advance
      molecular diagnostics.

PMID- 12067612
TI  - The value of microarray techniques for quantitative gene profiling in molecular
      diagnostics.
AB  - There has been an explosion of interest in microarray technologies that allow the
      quantification of whole-genome RNA expression data. The apparent correlation of
      expression profiles with clinically relevant parameters such as disease outcome
      has raised expectations with respect to the clinical usefulness of the data
      generated. Yet the accuracy and biological relevance of these data remain
      contentious, even in basic research applications. Therefore, numerous issues
      related to format, quality, validation and interpretation remain to be resolved
      before microarray profiling can become a diagnostic tool of clinical relevance
      for routine work.

PMID- 12067613
TI  - Molecular diagnostics of transmissible spongiform encephalopathies.
AB  - Clinical criteria for the diagnosis of sporadic, iatrogenic and variant
      Creutzfeldt-Jakob diseases are now available and show an excellent sensitivity
      and specificity ( approximately 98%). Post-mortem diagnosis, based upon the
      identification in the brain of the pathological conformer of the prion protein
      (PrP(Sc)), is also very accurate, and several diagnostic kits are now available
      that facilitate the immunochemical measurement of PrP(Sc). Several new molecular
      diagnostic techniques aimed at increasing the sensitivity and specificity of
      PrP(Sc) detection, and at identifying markers of disease that are other than
      PrP(Sc), are the subject of ongoing studies. The aim of these studies is to
      develop preclinical screening tests for the identification of infected, but still
      healthy, individuals. These tests are also badly needed to check the safety of
      blood or blood-derived products, and to ensure meat safety in European countries.

PMID- 12067614
TI  - Molecular diagnostics in infectious diseases and public health microbiology:
      cottage industry to postgenomics.
AB  - Molecular methods have been used increasingly over the past ten years to improve
      the sensitivity and speed of diagnosis in infectious diseases. Although their
      routine use is still limited to the detection of pathogens that are difficult to
      culture in vitro,'real-time' methods, commercial kits, quantification and
      automation will increase potential applications. Molecular methods are now widely
      used for epidemiological fingerprinting of isolates of public health importance.
      Sequence-based identification and strain typing, together with the development of
      tools that can probe for thousands of markers, will allow detailed strain
      fingerprinting to assist in disease management and control.

PMID- 12067615
TI  - The promise of biomarkers in cancer screening and detection.
AB  - Despite the recent decline in the incidence of cancer, long-term mortality rates
      remain unchanged. One of the most important factors in the survival of cancer is
      detection at an early stage. Clinical assays that detect the early events of
      cancer offer an opportunity to intervene and prevent cancer progression.
      Biomarkers are important molecular signatures of the phenotype of a cell that aid
      in early cancer detection and risk assessment. Although new information and
      technologies are clearly important for new biomarker discovery, we face major
      hurdles in translating new findings into clinical application. Here, we discuss
      examples of recent advances and limitations in cancer biomarker identification
      and validation, and the implications for cancer prevention.

PMID- 12067616
TI  - Toward molecular diagnostics of mood disorders in psychiatry.
AB  - Mental disorders are highly prevalent and often difficult to diagnose. There is a
      significant gap between advances in their pharmacotherapy and the present lack of
      objective biologic tests for diagnosis. The special complexity of diagnosis in
      psychiatry is related to the absence of objective diagnostic "gold standards", co
      morbidity, heterogeneity and equifinality, quantitative trait loci, and locus
      heterogeneity. Here, we review recent findings relating to diagnostic,
      pathophysiological, and linkage markers for mood disorders at the biochemical
      level involving monoamine neurotransmitters, hormones, and signal-transducing G
      proteins. Identification of biological diagnostic markers could enable
      segregating mood disorders to several biologically different subtypes. New-era
      methods and strategies involving genomics, proteomics, multi-marker approach and
      single nucleotide polymorphisms have the potential to revolutionize future
      diagnosis in psychiatry.

PMID- 12067617
TI  - Molecular diagnostics as a predictive tool: genetics of drug efficacy and
      toxicity.
AB  - There is a rapidly growing body of evidence linking genetic polymorphisms with
      functional changes in proteins that are responsible for the metabolism and
      disposition of many medications. Likewise, polymorphisms in genes encoding the
      targets of medications (e.g. receptors) can alter the pharmacodynamics of the
      drug response by changing receptor sensitivity. As a result, the inherited basis
      of drug effects is often polygenic in nature, and thus more challenging to
      define. However, technological advances, coupled with new insights into the
      molecular pharmacology of medications and the functional consequences of
      polymorphisms in the human genome, are providing the tools needed to elucidate
      genetic determinants of drug response, and translate functional genomics into
      personalized medicine.

PMID- 12067618
TI  - Genetic testing for disease susceptibilities: consequences for genetic
      counseling.
AB  - The role of genetic counseling in future testing for inherited susceptibilities
      for common diseases is debated. Currently, genetic testing, ideally supported by
      genetic counseling, is most often used to modify the assessment of genetic risk
      of Mendelian-inherited disease in high-risk individuals for the purpose of
      personal decision-making. By contrast, it is anticipated that genetic testing
      will be used to identify increased disease susceptibility in low-risk individuals
      for the purpose of instituting medical or lifestyle interventions to modify risk
      for future disease.

PMID- 12067622
TI  - Altered acetylation in polyglutamine disease: an opportunity for therapeutic
      intervention?
AB  - Recent investigations into polyglutamine diseases suggest that aberrant
      transcriptional regulation might be central to the molecular pathogenesis,
      perhaps because of inappropriate interaction between mutant proteins and
      important nuclear factors. Several groups have reported an interaction of mutant
      polyglutamine with histone acetylases, implicating defective acetylation as a
      cause of abnormal transcription. An important recent observation is that reversal
      of the acetylation defect with histone deacetylase inhibitors ameliorates
      polyglutamine toxicity in yeast, mammalian cell culture, and animal models. These
      encouraging findings suggest that a novel strategy--pharmacological restoration
      of histone acetylation-- could prove effective in treating this group of
      devastating illnesses.

PMID- 12067623
TI  - Healing a natural knockout of epithelial organogenesis.
AB  - Ectodermal dysplasias are a large group of rare genetic disorders with
      developmental abnormalities in skin, teeth, hair and nails. Many of them are
      clinically serious and impair the life of patients. The cloning of the gene for
      the most common of them, X-linked anhidrotic ectodermal dysplasia, in 1996 opened
      the door to dissect novel developmental pathways at the molecular level. Since
      then, several new genes and proteins with novel functions have been identified.

PMID- 12067629
TI  - Connexin mutations in hearing loss, dermatological and neurological disorders.
AB  - Gap junctions are important structures in cell-to-cell communication. Connexins,
      the protein units of gap junctions, are involved in several human disorders.
      Mutations in beta-connexin genes cause hearing, dermatological and peripheral
      nerve disorders. Recessive mutations in the gene encoding connexin 26 (GJB2) are
      the most common cause of childhood-onset deafness. The combination of mutations
      in the GJB2 and GJB6 (Cx30) genes also cause childhood hearing impairment.
      Although both recessive and dominant connexin mutants are functionally impaired,
      dominant mutations might have in addition a dominant-negative effect on wild-type
      connexins. Some dominant mutations in beta-connexin genes have a pleiotropic
      effect at the level of the skin, the auditory system and the peripheral nerves.
      Understanding the genotype-phenotype correlations in diseases caused by mutations
      in connexin genes might provide important insight into the mechanisms that lead
      to these disorders.

PMID- 12067630
TI  - Triggering caspase-independent cell death to combat cancer.
AB  - Caspase-mediated apoptosis is a major hindrance to tumour growth and metastasis.
      Accordingly, defects in signalling pathways leading to the activation of caspases
      are common in tumours. Moreover, many tumour cells can unexpectedly survive the
      activation of caspases. As a result, caspase-independent cell death programmes
      are gaining increasing interest among cancer researchers. The heterogeneity of
      cancer cells with respect to their sensitivity to various death stimuli further
      emphasizes the need for additional death pathways in the therapeutic control of
      cell death. An understanding of the molecular control of alternative death
      pathways is beginning to emerge, being comparable with that of the molecular
      anatomy of apoptosis at the time of the discovery of caspases less than a decade
      ago. Here, newly discovered triggers and molecular regulators of alternative cell
      death programmes are reviewed and their potential in future cancer therapy is
      discussed.

PMID- 12067631
TI  - Molecular insights into Friedreich's ataxia and antioxidant-based therapies.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease
      causing limb and gait ataxia and cardiomyopathy. The disease gene encodes a
      mitochondrial protein of unknown function, frataxin. The loss of functional
      frataxin is caused by a large GAA trinucleotide expansion in the first intron of
      the gene, thus impairing gene transcription. The lack of frataxin appears to
      result primarily in disabled recruitment of early antioxidant defenses, resulting
      in oxidative insult to the highly sensitive iron-sulfur proteins aconitase and
      three mitochondrial respiratory chain complexes (I-III). Accordingly, antioxidant
      based therapy appears promising in counteracting the course of the disease.

PMID- 12067632
TI  - Immunotherapy with ligands of natural killer T cells.
AB  - Natural killer T (NKT) cells are innate lymphocytes that share receptor
      structures and functions with conventional T cells and natural killer cells. NKT
      cells are specific for glycolipid antigens bound by the major histocompatibility
      complex class I-like protein CD1d. One striking property of NKT cells is their
      capacity to rapidly produce large amounts of cytokines in response to T-cell
      receptor engagement, suggesting that activated NKT cells can modulate adaptive
      immune responses. Recent pre-clinical studies have revealed significant efficacy
      of NKT-cell ligands such as the glycolipid alpha-galactosylceramide for treatment
      of metastatic cancers and infections, and for prevention of autoimmune diseases.
      These findings suggest that appropriate stimulation of NKT cells could be
      exploited for prevention or treatment of human diseases.

PMID- 12067633
TI  - The role of chaperones in polyglutamine disease.
AB  - The "triplet repeat" neurodegenerative diseases are linked by a common mode of
      pathogenicity, wherein a polyglutamine expansion within the relevant disease
      causing protein induces toxicity. Although details underlying pathogenesis are
      largely unknown, protein chaperones appear to be effective suppressors of
      toxicity in various experimental models. Understanding the protective role of
      chaperones might not only help us to understand the biology of polyglutamine
      toxicity, but also, and perhaps more importantly, inspire the design of novel
      therapeutic strategies.

PMID- 12067634
TI  - Parkinson's disease: one biochemical pathway to fit all genes?
AB  - Although originally discounted, hereditary factors have emerged as the focus of
      research in Parkinson's disease (PD). Genetic studies have identified mutations
      in alpha-synuclein and ubiquitin C-terminal hydrolase as rare causes of autosomal
      dominant PD and mutations in parkin as a cause of autosomal recessive PD.
      Functional characterization of the identified disease genes implicates the
      ubiquitin-mediated protein degradation pathway in these hereditary forms of PD
      and also in the more common sporadic forms of PD. Subsequent identification of
      further loci in familial PD and diverse genetic factors modulating the risk for
      sporadic PD point to substantial genetic heterogeneity in the disease. Thus, new
      candidate genes are expected to encode proteins either involved in ubiquitin
      mediated protein degradation or sequestrated in intracytoplasmic protein
      aggregations. Future identification of disease genes is required to confirm this
      hypothesis, thereby unifying the clinical and genetic heterogeneity of PD,
      including the common sporadic form of the disease, by one biochemical pathway.

PMID- 12067647
TI  - Mechanisms of chromatin assembly and transcription.
AB  - Fundamental mechanisms that regulate chromatin assembly and transcription have
      been elucidated recently using genetics and highly defined biochemical systems.
      Once DNA is packaged into chromatin, its function is controlled by the ordered
      recruitment of diverse enzymatic complexes that structurally remodel or
      chemically modify nucleosomes. Recent studies provide insight into the functional
      selectivity of chromatin-remodeling and -modifying complexes and how they act in
      specific combinations to regulate individual genes and cellular pathways.

PMID- 12067648
TI  - Chromatin as a eukaryotic template of genetic information.
AB  - In eukaryotes, chromatin is essential for heredity. Chromatin architecture is
      sometimes "epistatic" over the DNA and imparts a different heritable state to the
      same DNA sequence or the same functional state to unrelated DNA sequences. This
      has been documented recently in a wide variety of studies focused on regulation
      of the yeast mating type, the function of Polycomb and trithorax group proteins,
      the specification of eukaryotic centromeres and neocentromeres, and genomic
      imprinting.

PMID- 12067649
TI  - Centromeres and variant histones: what, where, when and why?
AB  - The CENP-A histone H3-like variants are centromere-specific histones found in all
      eukaryotes examined to date, from budding yeast to man. New experiments using
      antibodies, green fluorescent protein fusions, and epitope tags show that CENP-A
      replaces the major histone H3 subunits in a specialized histone octamer and that
      it does so with histones H4, and probably H2A and H2B. One of the classic
      hallmarks of chromatin molecular biology is that nucleosomes are deposited on DNA
      during replication in S phase. However, dramatic new results in mammalian and
      Drosophila cells show that CENP-A deposition is uncoupled from the replication of
      centromere DNA. Furthermore, genetic and phenotypic knockout experiments over the
      past year have demonstrated that the deposition of CENP-A at newly duplicated
      sister centromeres is an early step in the biogenesis of new centromeres and is
      required for the recruitment of other proteins to the centromere and kinetochore.
      In organisms with complex regional or holocentric centromeres, centromere
      identity was thought to be defined by the epigenetic state of centromere
      chromatin. Now, new experiments solidify this model and show that the epigenetic
      state can be spread in cis experimentally, creating a neocentromere, in a
      mechanism reminiscent of chromatin transcriptional silencing. Finally, a new
      report provides a glimpse into the potential regulation of CENP-A through
      specific post-translational phosphorylation, suggesting a broad level of control
      through histone tail modifications.

PMID- 12067650
TI  - The many faces of histone lysine methylation.
AB  - Diverse post-translational modifications of histone amino termini represent an
      important epigenetic mechanism for the organisation of chromatin structure and
      the regulation of gene activity. Within the past two years, great progress has
      been made in understanding the functional implications of histone methylation; in
      particular through the characterisation of histone methyltransferases that direct
      the site-specific methylation of, for example, lysine 9 and lysine 4 positions in
      the histone H3 amino terminus. All known histone methyltransferases of this type
      contain the evolutionarily conserved SET domain and appear to be able to
      stimulate either gene repression or gene activation. Methylation of H3 Lys9 and
      Lys4 has been visualised in native chromatin, indicating opposite roles in
      structuring repressive or accessible chromatin domains. For example, at the
      mating-type loci in Schizosaccharomyces pombe, at pericentric heterochromatin and
      at the inactive X chromosome in mammals, striking differences between these
      distinct marks have been observed. H3 Lys9 methylation is also important to
      direct additional epigenetic signals such as DNA methylation--for example, in
      Neurospora crassa and in Arabidopsis thaliana. Together, the available data
      strongly establish histone lysine methylation as a central modification for the
      epigenetic organisation of eukaryotic genomes.

PMID- 12067651
TI  - Blockers and barriers to transcription: competing activities?
AB  - In the eukaryotic cell active and inactive genes reside adjacent to one another
      and are modulated by numerous regulatory elements. Insulator elements prevent the
      misregulation of adjacent genes by restricting the effects of the regulatory
      elements to specific domains. Enhancer blockers prevent enhancers from
      inadvertently activating neighboring genes, and recent results suggest that they
      might function by a conserved mechanism across species. These elements appear to
      disrupt enhancer-promoter "communications" by interacting with the regulatory
      elements and sequestering these elements into specific regions of the nucleus
      thus rendering them non-functional. Barrier elements insulate active genes from
      neighboring heterochromatin and recent results suggest that they function by
      specific localized recruitment of acetyltransferases that antagonize the spread
      of heterochromatin-associated deacetylases, thus preventing the propagation of
      heterochromatin.

PMID- 12067652
TI  - The SMN complex, an assemblyosome of ribonucleoproteins.
AB  - Spinal muscular atrophy is a common, often lethal, neurodegenerative disease that
      results from low levels of, or loss-of-function mutations in, the SMN (survival
      of motor neurons) protein. SMN oligomerizes and forms a stable complex with five
      additional proteins: Gemins 2-6. SMN also interacts with several additional
      proteins referred to as "substrates". Most of these substrates contain a domain
      enriched in arginine and glycine residues (the RG-rich domain), and are
      constituents of different ribonucleoprotein complexes. Recent studies revealed
      that the substrates can be modified by an arginine methyltransferase complex, the
      methylosome. This forms symmetrical dimethylarginines within the RG-rich domains
      of the substrates, thereby converting them to high-affinity binders of the SMN
      complex, and most likely providing regulation of the ribonucleoprotein assembly
      processes.

PMID- 12067653
TI  - Making ribosomes.
AB  - The past year has seen dramatic changes in our understanding of ribosome
      synthesis, fuelled largely by advances in proteomic analysis. It is now possible
      to outline the pathway of ribosome assembly, which is highly dynamic and involves
      a remarkable separation of the factors involved in the synthesis of the 40S and
      60S ribosomal subunits. Around 140 identified, non-ribosomal proteins are
      currently implicated in post-transcriptional ribosome synthesis in yeast.

PMID- 12067654
TI  - Biogenesis of small nucleolar ribonucleoproteins.
AB  - Eukaryotic cells contain a very complex population of small nucleolar RNAs. They
      function, as small nucleolar ribonucleoproteins, in pre-ribosomal RNA processing
      reactions, and also guide methylation and pseudouridylation of ribosomal RNA,
      spliceosomal small nuclear RNAs, and possibly other cellular RNAs. Synthesis of
      small nucleolar RNAs frequently follows unusual strategies. Some newly discovered
      brain-specific small nucleolar RNAs of unknown function are encoded in introns of
      tandemly repeated units, expression of which is paternally imprinted. Recent
      studies of the protein components and factors participating in small nucleolar
      ribonucleoprotein assembly have revealed interesting connections with other
      classes of cellular ribonucleoproteins such as spliceosomal small nuclear
      ribonucleoproteins and telomerase. Cajal bodies emerge as nuclear structures
      important for the biogenesis and function of small nucleolar ribonucleoproteins.

PMID- 12067655
TI  - Nucleocytoplasmic transport: cargo trafficking across the border.
AB  - Transport of macromolecules between the cytoplasm and the nucleus is mediated by
      at least three different classes of soluble transport receptors, members of the
      importin-beta protein family, the Mex67/Tap family and the small nuclear
      transport factor 2 (NFT2). All nuclear transport factors can bidirectionally
      traverse the nuclear pore complex through specific interactions with
      phenylalanine/glycine-rich nuclear pore complex components. Recent kinetic and
      structural analyses revealed novel insight into the details of these
      interactions. In addition, new biochemical and genetic studies have dramatically
      improved our understanding of ribosomal and messenger RNA export, unveiling a
      tight coupling between RNA processing and transport.

PMID- 12067656
TI  - The mRNA assembly line: transcription and processing machines in the same
      factory.
AB  - Processing of RNA precursors to their mature form often occurs co
      transcriptionally. Consequently, the ternary complex of DNA template, RNA
      polymerase and nascent RNA chain is the physiological substrate for factors that
      modify the nascent RNA by capping, splicing and cleavage/polyadenylation. mRNA
      production is thought to occur within a "factory" that contains the RNA
      polymerase II transcription machine and the processing machines. Newly discovered
      protein-protein contacts between RNA polymerase and factors that process mRNA
      precursors are beginning to illuminate how the "mRNA factory" works.

PMID- 12067657
TI  - SINEs and LINEs: the art of biting the hand that feeds you.
AB  - SINEs and LINEs are short and long interspersed retrotransposable elements,
      respectively, that invade new genomic sites using RNA intermediates. SINEs and
      LINEs are found in almost all eukaryotes (although not in Saccharomyces
      cerevisiae) and together account for at least 34% of the human genome. The
      noncoding SINEs depend on reverse transcriptase and endonuclease functions
      encoded by partner LINEs. With the completion of many genome sequences, including
      our own, the database of SINEs and LINEs has taken a great leap forward. The new
      data pose new questions that can only be answered by detailed studies of the
      mechanism of retroposition. Current work ranges from the biochemistry of reverse
      transcription and integration invitro, target site selection in vivo,
      nucleocytoplasmic transport of the RNA and ribonucleoprotein intermediates, and
      mechanisms of genomic turnover. Two particularly exciting new ideas are that
      SINEs may help cells survive physiological stress, and that the evolution of
      SINEs and LINEs has been shaped by the forces of RNA interference. Taken
      together, these studies promise to explain the birth and death of SINEs and
      LINEs, and the contribution of these repetitive sequence families to the
      evolution of genomes.

PMID- 12067658
TI  - Mechanisms of chromosome-end protection.
AB  - Telomeres must protect chromosome ends from being recognized and processed as
      double-strand breaks. Identification of the factors involved in end protection,
      and the mechanisms by which they "cap" chromosome termini, is crucial in
      understanding how the cell distinguishes between a double-strand break and a
      normal telomere end. Recent work has characterized the similarities and potential
      differences between the pathways utilized by multiple organisms in maintaining
      telomere ends. One unifying concept that has clearly emerged is that chromosome
      end protection is necessary in maintaining genetic stability and preventing
      oncogenesis.

PMID- 12067659
TI  - The nuclear envelope, lamins and nuclear assembly.
AB  - The nuclear lamina is composed of both A- and B-type lamins and lamin-binding
      proteins. Many lamin-binding proteins are integral proteins of the inner nuclear
      membrane. Lamins and inner nuclear membrane proteins are important for a variety
      of cell functions, including nuclear assembly, replication, transcription, and
      nuclear integrity. Recent advances in the field in the past year include the
      identification of a family of spectrin-repeat-containing inner nuclear membrane
      proteins and other novel inner-membrane proteins, and the discovery of a nuclear
      membrane fusion complex. There is also growing evidence that A- and B-type lamins
      and their binding partners have distinct roles during nuclear assembly and
      interphase.

PMID- 12067660
TI  - Bi-orienting chromosomes on the mitotic spindle.
AB  - For the proper segregation of sister chromatids before cell division, each sister
      kinetochore must attach to microtubules that extend to opposite spindle poles.
      This process is called bipolar microtubule attachment or chromosome bi
      orientation. The mechanism for chromosome bi-orientation lies at the heart of
      chromosome segregation, but is still poorly understood. Recent studies suggest
      that cells can promote bi-orientation by re-orienting kinetochore-spindle pole
      connections.

PMID- 12067661
TI  - Nuclear organisation and gene expression.
AB  - The development of increasingly sophisticated tools to track chromosomes and
      proteins in living cells offers the possibility of visualising gene regulation in
      the nucleus with minimal distortion. This, in conjunction with powerful genetic
      approaches available in yeast, is beginning to allow functional definition of
      nuclear "compartments".

PMID- 12067662
TI  - Replication timing and transcriptional control: beyond cause and effect.
AB  - In general, transcriptionally active euchromatin replicates during the first half
      of S phase, whereas silent heterochromatin replicates during the second half.
      Moreover, changes in replication timing accompany key stages of development.
      Although there is not a strict correlation between replication timing and
      transcription per se, recent results reveal a strong relationship between
      heritably repressed chromatin and late replication that is conserved in all
      eukaryotes. A long-standing question is whether replication timing dictates the
      structure of chromatin or vice versa. Mounting evidence supports a model in which
      replication timing is both cause and consequence of chromatin structure by
      providing a means to inherit chromatin states that, in turn, regulate replication
      timing in the subsequent cell cycle. Moreover, new findings relating aberrations
      in replication timing to defects in centromere function, chromosome cohesion and
      genome instability suggest that the role of replication timing extends beyond its
      relationship to transcription. Novel systems in both yeasts and mammals are
      finally beginning to reveal some of the determinants that regulate replication
      timing, which should pave the way for a long-anticipated molecular dissection of
      this complex liaison.

PMID- 12067664
TI  - The true cost of the nuclear deterrent.

PMID- 12067667
TI  - US citizens exposed to radiation fallout during Cold War tests.

PMID- 12067668
TI  - Testicular cancer: risks of treatment vs risks of recurrence.

PMID- 12067669
TI  - Consuming tomato products may reduce prostate-cancer risk.

PMID- 12067671
TI  - Agent Orange no longer linked to childhood AML.

PMID- 12067675
TI  - New drug slows prostate-cancer progression.

PMID- 12067676
TI  - 'Rub on' treatment for basal-cell carcinoma.

PMID- 12067677
TI  - Methylnaltrexone reverses opioid-induced constipation.

PMID- 12067679
TI  - Provision of cancer care in Eastern Europe.

PMID- 12067680
TI  - A patients right to know?

PMID- 12067682
TI  - The evolution of tamoxifen therapy in breast cancer: selective oestrogen-receptor
      modulators and downregulators.
AB  - Tamoxifen is the most widely used hormonal treatment for all stages of breast
      cancer and has been approved for the prevention of breast cancer in high-risk
      women. The observation that tamoxifen acts as an antioestrogen on the breast but
      has paradoxical oestrogenic effects on bones and lipids heralded the development
      of the selective oestrogen-receptor modulators (SERM). Raloxifene, another of
      these drugs, is being used to prevent osteoporosis in postmenopausal women, but
      it seems, like tamoxifen, to prevent breast cancer. The molecular basis for these
      target-site-specific actions remains unclear but may involve the relative
      expressions of coregulatory proteins in target tissues. Several new SERM agents
      are in clinical development in an attempt to decrease the unwanted effects.
      Furthermore, two different classes of hormonal agents, the aromatase inhibitors
      and oestrogen-receptor downregulators, which have no oestrogen-like properties at
      any site, are promising new treatments for breast cancer.

PMID- 12067683
TI  - Use of minimally invasive oesophagectomy for cancer of the oesophagus.
AB  - Minimally invasive surgery has had a great effect on all branches of surgery,
      although its use for oesophageal cancer is controversial because of the technical
      complexity of the techniques involved and its uncertain benefits. We review the
      minimally invasive techniques that have been used for oesophagectomy. The methods
      are certainly feasible and can be done safely in experienced centres, but
      postoperative morbidity and mortality rates are not substantially reduced by the
      procedure. There are also concerns regarding the adequacy of tumour clearance.
      Further evaluation of the role of minimally invasive techniques in oesophageal
      cancer would require larger scale studies, preferably randomised controlled
      trials, in experienced centres. However, given that survival rates have not
      changed, proving that minimally invasive techniques are more effective than
      conventional methods of oesophagectomy, will be a difficult task.

PMID- 12067684
TI  - Clinical management of dyspnoea.
AB  - Dyspnoea, defined as a sensation of an uncomfortable awareness of breathing, is
      one of the most frightening and distressing symptoms for patients with cancer. It
      is very common in cancer patients with and without direct lung involvement. The
      gold standard of diagnosis and assessment is the patient's self-report.
      Measurements of respiratory rate, oxygen saturation, and arterial blood gases do
      not measure dyspnoea. Fast, safe, and effective relief of the symptom is possible
      whether or not identifiable reversible causes exist. Opioids are the first line
      of therapy for such relief. Medical management can be directed at the underlying
      cause when the potential benefits outweigh the burdens of such treatment. In rare
      cases for which symptomatic treatment does not control dyspnoea to the patient's
      satisfaction, sedation is an effective, ethical option.

PMID- 12067685
TI  - Mediastinal (thymic) large B-cell lymphoma: where do we stand?
AB  - Mediastinal (thymic) B-cell lymphoma (MBL) is a locally highly aggressive tumour
      that was first definitively described in the early 1980s. The incidence of MBL is
      low, which made disease characterisation difficult initially. However, MBL has
      several peculiar clinical, morphological, immunological, and genetic features.
      Collectively, these characteristics distinguish it from other diffuse, large B
      cell lymphomas. Consequently, MBL has become a defined subtype of diffuse large B
      cell lymphoma with its own code (9679/3) in the International Classification of
      Diseases. New insights into the biological and clinical aspects of MBL have been
      gained from the study of large numbers of cases. Nevertheless, the histogenesis
      of the disease is not yet fully understood. We review the available data on MBL
      with special emphasis on its morphological, immunological, and genetic
      properties. Also discussed are recent data on molecular genetics, biology, and
      treatment.

PMID- 12067686
TI  - Culprit and victim -- DNA topoisomerase II.
AB  - The phylogenetic antiquity of DNA topoisomerases indicates their vital function.
      Structure and maintenance of genomic DNA depend on the activity of these enzymes,
      and without them DNA replication and cell division are impossible. Topoisomerase
      II alpha has therefore become the main target of many antitumour therapy
      regimens, even though the exact mechanism of cell killing remains elusive. The
      success of this approach is limited by the development of spontaneous resistance,
      and drug-induced DNA damage can increase malignancy. Nevertheless, the combined
      use of topoisomerase-inhibiting drugs with different mechanisms of action
      promises to improve particular treatment designs. The degree of topoisomerase II
      expression in tumours may predict the clinical course and responsiveness to
      therapy.

PMID- 12067687
TI  - Cancer causation: the Darwinian downside of past success?
AB  - Causal mechanisms in all diseases are diverse and multifactorial, but medical
      scientists, as pragmatists, inevitably focus on limited or circumscribed
      components of pathogenetic puzzles. In cancer, epidemiologists have traditionally
      sought to incriminate exposures; geneticists uncover inherited susceptibility;
      and molecular biologists deconstruct the proximal mechanisms of cell
      transformation. Molecular epidemiology promises to deliver new insights in terms
      of gene-environment interactions. Each of these endeavours has undeniably
      provided rich dividends and insights into cancer causation, but are these likely
      to be sufficient as a coherent explanation of our vulnerability to cancer? I
      suggest that the biological plausibility of causal mechanisms would benefit from
      a historical, evolutionary perspective. The essential argument is that genes or
      gene variants and phenotypic traits that were adaptively selected in the past as
      advantageous now contribute crucially to cancer because of their mismatch with
      current environmental and social circumstances. The risk attributes of skin
      pigmentation and some dietary factors in cancer can be plausibly interpreted
      within this context. A case is made here for a Darwinian perspective on breast
      and prostate cancers, for which current understanding of causation is limited and
      contentious.

PMID- 12067688
TI  - Percutaneous minimally invasive stereotactic primary radiotherapy for breast
      cancer.

PMID- 12067692
TI  - Crystal-gazing.

PMID- 12067693
TI  - Advance movement preparation of eye, foot, and hand: a comparative study using
      movement-related brain potentials.
AB  - The present study was designed to test the inter-relationship between generalized
      motor programs (GMPs) and movement preparation by asking participants to perform
      movements with eye, foot, or hand. In two independent experiments a response
      precuing task was employed that combined the recording of movement-related brain
      potentials (MRPs) with dipole source analysis. Behavioral results indicated the
      utilization of advance information about movement direction and effector. When
      eye and hand movements were involved (experiment1) partial advance information
      about response side but not effector induced parallel motor programming of eye
      and hand at an abstract but not effector-specific level. In contrast, when
      partial precues specified side of a forthcoming hand or foot movement (experiment
      2) foot and hand were prepared in parallel both at abstract and at effector
      specific levels of motor programming. Consistent with the GMP view, these results
      indicate that effector-specific preparation is possible even when the effector is
      not yet known as long as a common motor program controls the demanded movements.
      However, because parallel specification of divergent movement pattern (eye, hand)
      at an abstract level was not predicted by the GMP, we propose a model of advance
      movement preparation that takes into account neurofunctional considerations.

PMID- 12067694
TI  - Motor distal component and pragmatic representation of objects.
AB  - In this study, we tested whether in certain experimental conditions the distal
      and proximal motor components may dissociate in action imitation, and how the
      distal component and the object representation may interact. Experiments 1-3 were
      carried out using a dual task procedure in which an action span and a motor
      suppression were coupled. In Experiment 1, it was shown that action spans were
      affected more by a distal movement (e.g. distal motor suppression) than by a
      proximal movement (proximal motor suppression). In Experiment 2, it was
      demonstrated that the reduction of the action spans was not due to the distal
      motor suppression being more difficult than the proximal motor suppression. In
      Experiment 3, pantomimes were replaced with the corresponding objects and the
      participants were asked to mime the objects, reproducing the appropriate actions.
      During the presentation of the objects, the participants were engaged in a motor
      suppression that was performed either by the hand or by the arm. The distal motor
      suppression reduced the pantomime span more significantly than the proximal motor
      suppression. Experiment 4 showed that the spans of pantomimes of objects shown in
      Experiment 3 are longer when participants do not perform motor suppressions. Our
      results suggest that in normal subjects a difference between the distal and the
      proximal motor component can be observed under dual task conditions and that
      distal motor suppression seems to interfere both with the encoding of action and
      with pragmatic representation of objects.

PMID- 12067695
TI  - Sex differentiates the role of emotional prosody during word processing.
AB  - The meaning of a speech stream is communicated by more than the particular words
      used by the speaker. For example, speech melody, referred to as prosody, also
      contributes to meaning. In a cross-modal priming study we investigated the
      influence of emotional prosody on the processing of visually presented positive
      and negative target words. The results indicate that emotional prosody modulates
      word processing and that the time-course of this modulation differs for males and
      females. Women show behavioural and electrophysiological priming effects already
      with a small interval between the prosodic prime and the visual target word. In
      men, however, similar effects of emotional prosody on word processing occur only
      for a longer interval between prime and target. This indicates that women make an
      earlier use of emotional prosody during word processing as compared to men.

PMID- 12067696
TI  - Cognitive impairment in amyotrophic lateral sclerosis: evidence from
      neuropsychological investigation and event-related potentials.
AB  - The presence of subclinical cognitive impairment in patients with amyotrophic
      lateral sclerosis (ALS) is investigated using neuropsychological assessment and
      event-related potential recordings (ERP). An extensive battery of
      neuropsychological tests assessing the domains of attention, memory, language,
      visuo-spatial and executive functions were administered to 20 non-demented
      patients with sporadic ALS and 13 age- and education-matched healthy control
      subjects. Mismatch negativity (MMN), P3b, P3a (novelty P300) and contingent
      negative variation (CNV) were recorded. ALS patients were significantly impaired
      in tests of working memory, sustained attention, response inhibition, naming,
      verbal fluency and complex visuo-spatial processing. The memory impairment seemed
      to be secondary to deficits in forming learning strategies and retrieval. In ERP
      recordings, P3a and P3b amplitudes of ALS patients were lower compared with the
      controls, P3a latencies were significantly longer and mean CNV amplitudes were
      higher. These results indicate subclinical impairment of cognitive functions in
      patients with ALS. The pattern of cognitive impairment suggests the dysfunction
      of the frontal network.

PMID- 12067697
TI  - Comparing the brain areas supporting nondeclarative categorization and
      recognition memory.
AB  - Brain areas associated with both nondeclarative categorization and recognition
      memory were identified and contrasted using functional magnetic resonance imaging
      (fMRI) of healthy volunteers. Activity during dot-pattern categorization and
      recognition were compared with a control task (counting dots) in two separate
      groups of participants (n=5 each). The network of areas associated with
      nondeclarative categorization was found to include bilateral inferior prefrontal
      and parietal cortical areas that have been implicated in several other studies of
      categorization. During recognition, increased activity was found in posterior
      visual areas, the precuneus, posterior cingulate and right prefrontal cortex.
      Using the common control condition as a reference, recognition and categorization
      were contrasted and recognition was found to evoke more activity in posterior
      early visual cortex, the precuneus, right medial temporal lobe and right dorso
      lateral prefrontal cortex. Previous research has implicated changes in visual
      representation in learning a category of dot-pattern by comparing activity evoked
      by categorical and non-categorical stimuli. The current findings support those
      results and additionally identify brain areas active during categorization that
      are involved in expressing this category knowledge.

PMID- 12067698
TI  - Visual motion stimulation, but not visually induced perception of self-motion,
      biases the perceived direction of verticality.
AB  - Large-field torsional optokinetic stimulation is known to affect the perceived
      direction of gravity with verticality judgements deviating towards the direction
      of visual stimulus rotation. The present study aimed to replicate this effect and
      to examine it further by subjecting participants to optokinetic stimulation in
      roll, resulting in spontaneous alternations between the perception of object
      motion and that of contradirectional self-motion (vection), as reported by the
      subjects. Simultaneously, subjects were oscillated laterally in a flight
      simulator and indicated their perception of postural verticality. Results
      confirmed that rotation of the visual environment in the frontal plane biases the
      perceived orientation of gravity towards the direction of visual stimulus motion.
      However, no differential effect of perceptual state on postural verticality was
      obtained when contrasting verticality judgements made during the perception of
      object-motion with those obtained during reported self-motion perception. This
      finding is likely to reflect a functional segregation of central nervous visual
      vestibular subsystems that process the perception of self-tilt and that of self
      rotation to some degree independently.

PMID- 12067699
TI  - Medial agranular cortex activity related to event-related potential generation in
      the rat.
AB  - Neuronal firings and local field potentials were recorded in the medial agranular
      cortex (Fr2) together with surface event-related potentials (ERPs) during an
      auditory oddball task in the rat. 10/32 Fr2 neurons showed a sustained increase
      in firing frequency in response to target tone (100-615 ms from the tone onset)
      with an activation peak corresponding to surface P100 component. At the intra
      cortical recording site, local P100 component was observed with greater peak
      amplitude than that on the surface. No conspicuous neuronal response was evoked
      by non-target tone. The results suggest that the rat Fr2 is involved in stimulus
      discrimination and generation of ERPs during the oddball task.

PMID- 12067700
TI  - A perceptual level mechanism of the inhibition of return in oculomotor planning.
AB  - A motor response to a visual target presented at a precued spatial location is
      facilitated if the target is presented shortly after the cue and inhibited when
      the cue target onset asynchrony approaches a few hundred milliseconds. The latter
      effect is termed inhibition of return (IOR). It is suggested that IOR provides an
      important strategy for effective search in our visual environment. Despite
      studies demonstrating IOR in a number of behavioral tasks, its neural mechanism
      has remained elusive. As a fundamental step toward understanding these
      mechanisms, the current study examines whether IOR mainly involves a perceptual
      or a motor process. We conducted a series of experiments, in which the target
      instructed saccades to the cued or to a different location. In each experiment,
      we observed a similar pattern of IOR when the target followed the cue, but not
      when the saccade was directed to the cued location. In another two experiments,
      we demonstrated that the magnitude and temporal profile of IOR varied depending
      on whether an eye movement or a manual response was involved. Overall, the
      present study suggests that IOR results predominantly from a perceptual level
      mechanism, with its magnitude and time course modulated by the activation of
      specific motor effectors. We discuss the implications of these results for
      attention gating of perceptual inputs and for mechanisms of visuomotor control.

PMID- 12067702
TI  - Cortical processing of speech sounds and their analogues in a spatial auditory
      environment.
AB  - We used magnetoencephalographic (MEG) measurements to study how speech sounds
      presented in a realistic spatial sound environment are processed in human cortex.
      A spatial sound environment was created by utilizing head-related transfer
      functions (HRTFs), and using a vowel, a pseudo-vowel, and a wide-band noise burst
      as stimuli. The behaviour of the most prominent auditory response, the cortically
      generated N1m, was investigated above the left and right hemisphere. We found
      that the N1m responses elicited by the vowel and by the pseudo-vowel were much
      larger in amplitude than those evoked by the noise burst. Corroborating previous
      observations, we also found that cortical activity reflecting the processing of
      spatial sound was more pronounced in the right than in the left hemisphere for
      all of the stimulus types and that both hemispheres exhibited contralateral
      tuning to sound direction.

PMID- 12067701
TI  - Functional MRI of motor sequence acquisition: effects of learning stage and
      performance.
AB  - Neural networks of motor control are well understood and the motor domain
      therefore lends itself to the study of learning. Neuroimaging of motor learning
      has demonstrated fronto-parietal, subcortical, and cerebellar involvement.
      However, there is conflicting evidence on the specific functional contributions
      of individual regions and their relative importance for early and advanced stages
      of learning. Using functional MRI (fMRI), we examined hemodynamic effects in
      seven right-handed men during brief episodes of explicit learning of novel six
      digit sequences (experiments 1 and 2) and during prolonged learning of an eight
      digit sequence (experiment 3), all performed with the dominant hand. Brief
      episodes of new learning were predominantly associated with bilateral activations
      in premotor and supplementary motor areas, superior and inferior parietal
      cortices, and anterior cerebellum. In experiment 2, which included a control
      condition matched for complexity of motor execution, we also found unexpectedly
      strong activation in the bilateral inferior frontal lobes. In experiment 3,
      analysis of task by learning stage interactions showed greater involvement of the
      bilateral superior parietal lobes, the right middle frontal gyrus, and the left
      caudate nucleus during early stages, whereas left occipito-temporal and superior
      frontal cortex as well as the bilateral parahippocampal region were more
      activated during late learning stages. Analysis of task by performance
      interactions (based on each subject's response times and accuracy during each
      scan) showed effects in bilateral fronto-polar, right hippocampal, and anterior
      cerebellar regions associated with high levels of performance, as well as inverse
      effects in bilateral occipito-parietal regions. We conclude that superior
      parietal and occipital regions are most intensely involved in visually driven
      explicit digit sequence learning during early stages and low performance, whereas
      later stages of acquisition and higher levels of performance are characterized by
      stronger recruitment of prefrontal and mediotemporal regions.

PMID- 12067703
TI  - Functional anatomy of top-down visuospatial processing in the human brain:
      evidence from rTMS.
AB  - The hypothesis was tested that visuospatial mental imagery relies on processing
      in the posterior parietal lobe. Using repetitive transcranial magnetic
      stimulation (rTMS) in a cross-over, sham-controlled design, we compared
      involvement of right posterior parietal cortex with primary visual cortex.
      Subjects received rTMS over the parietal and occipital cortices during 20 min,
      after which they performed a behaviorally controlled visuospatial mental imagery
      task. Performance deteriorated significantly after rTMS over the parietal, but
      not occipital, cortex. These data support a causal link between parietal
      activation and top-down spatial processing.

PMID- 12067704
TI  - Hemispheric asymmetries in auditory evoked neuromagnetic fields in response to
      place of articulation contrasts.
AB  - A growing body of evidence indicates bilateral but asymmetric hemispheric
      involvement in speech perception. We used magnetoencephalography to record
      neuromagnetic evoked responses in 10 adults to consonant-vowel syllables that
      differ in a single phonetic feature, place of articulation. We report
      differential activation patterns in M100 latency, with larger differences in the
      right hemisphere than the left. These findings suggest that left and right
      auditory fields make differential contributions to speech processing.

PMID- 12067705
TI  - A role for calcium in sphingosine 1-phosphate-induced phospholipase D activity in
      C2C12 myoblasts.
AB  - Receptor-regulated phospholipase D (PLD) is a key signaling pathway implicated in
      the control of fundamental biological processes. Here evidence is presented that
      in addition to protein kinase C (PKC) and Rho GTPases, Ca(2+) response evoked by
      sphingosine 1-phosphate (S1P) also participates to the enzyme regulation. Ca(2+)
      was found critical for PKC(alpha)-mediated PLD activation. Moreover, S1P-induced
      PLD activity resulted diminished by calmodulin inhibitors such as W-7 and
      CGS9343B implicating its involvement in the process. A plausible candidate for
      Ca(2+)-dependent PLD regulation by S1P was represented by calcineurin, in view of
      the observed reduction of the stimulatory effect by cyclosporin A. In contrast,
      monomeric GTP-binding protein Ral was translocated to membranes by S1P in a
      Ca(2+)-independent manner, ruling out its possible role in agonist-mediated
      regulation of PLD.

PMID- 12067706
TI  - Critical role of protein kinase C alpha and calcium in growth factor induced
      activation of the Na(+)/H(+) exchanger NHE1.
AB  - The ubiquitously expressed Na(+)/H(+) exchanger (NHE1) plays an important role in
      the regulation of the intracellular pH. Induction of NHE activity by phorbol
      esters and inhibition of growth factor-mediated stimulation of the NHE by protein
      kinase C (PKC) inhibitors suggest an implication of PKCs in the regulation of the
      NHE. Expression of PKC isotype-specific dominant negative and constitutively
      active mutants or downregulation of PKC by isotype-specific antisense
      oligonucleotides revealed that stimulation by epidermal growth factor (EGF) or
      phorbol ester of the NHE in NIH3T3 cells is a PKC(alpha)-specific effect.
      Elevation of cytoplasmic calcium by a Ca(2+) ionophore or thapsigargin causes a
      growth factor-independent stimulation of the NHE predominantly mediated by
      calcium/calmodulin kinase II. It is concluded that in NIH3T3 cells overexpressing
      the EGF receptor (EGFR6 cells), EGF requires cPKC(alpha) for the activation of
      the NHE, while calcium/calmodulin-dependent kinases are essential in thapsigargin
      induced stimulation of the NHE.

PMID- 12067707
TI  - Functional analysis of MRP1 cloned from bovine.

PMID- 12067708
TI  - Direct modulation of volume-regulated anion channels by Ca(2+) chelating agents.
AB  - Ca(2+) chelating agents are widely used in biological research for Ca(2+)
      buffering. Here we report that BAPTA, EDTA and HEDTA produce fast, reversible,
      voltage-dependent inhibition of swelling-activated Cl(-) current (I(Cl,swell)) in
      LNCaP prostate cancer epithelial cells that is unrelated to their Ca(2+) binding.
      BAPTA was the most effective (maximal blockade 67%, IC(50)=70 microM, at +100 mV)
      followed by EDTA and HEDTA. I(Cl,swell) blockade by EDTA was pH-dependent. BAPTA
      blocked I(Cl,swell) also in other cell types. We conclude that Ca(2+) chelating
      agents block I(Cl,swell) by acting directly on the underlying channel, and that
      the negative charge of the free chelator form is critical for the blockade.

PMID- 12067709
TI  - Protein kinase A balances the growth factor-induced Ras/ERK signaling.
AB  - Protein kinase A (PKA) has been proposed to regulate the signal transduction
      through the Ras/extracellular-regulated kinase (ERK) pathway. Here we demonstrate
      that when the PKA activity was inhibited prior to growth factor stimulus the
      signal flow through the Ras/ERK pathway was significantly increased. Furthermore,
      the data indicated that this PKA-mediated regulation was simultaneously targeted
      to the upstream kinase Raf-1 and to the ERK-specific phosphatase mitogen
      activated protein kinase phosphatase-1 (MKP-1). Moreover, our data suggested that
      the level of PKA activity determined the transcription rate of mkp-1 gene,
      whereas the Ras/ERK signal was required to protect the MKP-1 protein against
      degradation. These results point to a tight regulatory relationship between PKA
      and the growth factor signaling, and further suggest an important role for basal
      PKA activity in such regulation. We propose that PKA adjusts the activity of the
      Ras/ERK pathway and maintains it within a physiologically appropriate level.

PMID- 12067710
TI  - TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF
      kappaB activation.
AB  - Proteins containing the caspase recruiting domain (CARD) have emerged as critical
      regulators of different signal transduction pathways, including those controlling
      apoptosis and activation of necrosis factor (NF)-kappaB transcription factor.
      TUCAN/CARDINAL is a recently identified CARD-containing protein involved in
      regulation of caspases and NF-kappaB activation. We find that TUCAN/CARDINAL
      associates with DRAL, a p53-responsive gene implicated in induction of apoptosis.
      We also show that, whereas TUCAN/CARDINAL exerts a suppressive effect on NF
      kappaB activity, expression of DRAL results in enhancement of NF-kappaB
      activation. Thus, our observations suggest that DRAL and TUCAN/CARDINAL may
      participate in a regulatory mechanism that coordinates cellular responses
      controlled by NF-kappaB transcription factor.

PMID- 12067711
TI  - Regulation of the Werner helicase through a direct interaction with a subunit of
      protein kinase A.
AB  - Werner syndrome is a hereditary disease characterized by cancer predisposition,
      genetic instability, and the premature appearance of features associated with
      normal aging. At the molecular level this syndrome has been related to mutations
      in the Werner helicase, a member of the RecQ family of DNA helicases which are
      required to maintain genomic stability in cells. Here we show by a yeast two
      hybrid screen that the Werner helicase can directly interact with the regulatory
      subunit (RIbeta) of cAMP protein kinase A (PKA). We confirm that this interaction
      occurs in vivo. Interestingly, serum withdrawal causes a redistribution of the
      Werner helicase within the nucleus of mammalian cells. Raising intracellular cAMP
      levels or increased expression of the regulatory but not the catalytic subunit of
      PKA inhibits this nuclear redistribution stimulated by serum deprivation. These
      results suggest that similar to lower organisms, gene products linked to genomic
      instability and aging may be directly regulated by growth factor-sensitive, PKA
      dependent pathways.

PMID- 12067712
TI  - Overexpression of human metallothionein-III prevents hydrogen peroxide-induced
      oxidative stress in human fibroblasts.
AB  - Metallothioneins (MT) are ubiquitous low molecular weight metal binding proteins
      that may act as antioxidants. In the present study, the cloned human MT-III
      coding region was permanently transfected into GM00637 cells in order to
      investigate the antioxidative effects of this brain-specific MT isoform.
      GM00637/MT-III cells overexpressed MT-III mRNA versus pcDNA3 plasmid-transfected
      control cells (GM00637). When challenged with H(2)O(2), the GM00637/MT-III cells
      displayed significantly more resistance than the GM00637 cells, as determined by
      cell cytotoxicity, lactate dehydrogenase leakage, and lipid peroxidation. In
      addition, the GM00637/MT-III cells were highly protected from the H(2)O(2)
      induced production of reactive oxygen species and DNA damage. These results
      directly support the antioxidative role of MT-III, and demonstrate MT-III can
      scavenge free oxygen radicals and protect cells from oxidative stress.

PMID- 12067713
TI  - PDGF induces osteoprotegerin expression in vascular smooth muscle cells by
      multiple signal pathways.
AB  - Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Recent reports
      suggest that OPG may function as a protector of arterial calcification and
      survival of endothelial cells. However, the role and expression of OPG in
      vascular wall is unclear. Here we report that OPG was highly expressed in
      vascular smooth muscle cells (VSMC) but not in endothelial cells. Platelet
      derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II,
      tumor necrosis factor alpha and interleukin-1beta upregulated OPG expression in
      VSMC. Moreover, inhibition of phosphatidylinositol 3-kinase/Akt or P38-signal
      pathway abrogated PDGF-induced OPG expression. Our results suggest that OPG may
      be an important determinant of vascular homeostasis.

PMID- 12067714
TI  - Direct interaction of Frizzled-1, -2, -4, and -7 with PDZ domains of PSD-95.
AB  - In Drosophila, the frizzled gene plays a critical role in the establishment of
      tissue polarity, but the function of the Frizzled family of proteins in mammals
      is largely unknown. Recent evidence suggested that Frizzleds are receptors for
      the Wnt family of secreted glycoproteins which are involved in cell fate
      determination. However, it is unclear how Frizzled receptors transduce Wnt
      signals to intracellular signaling components. Here we show that the mouse
      Frizzled-1, -2, -4 and -7 can bind to proteins of the PSD-95 family, which are
      implicated in the assembly and localization of multiprotein signaling complexes
      in the brain. Moreover, PSD-95 can form a ternary complex with Frizzled-2 and the
      adenomatous polyposis coli protein, a negative regulator of Wnt signaling,
      suggesting that members of the PSD-95 family may serve to recruit intracellular
      signaling molecules of the Wnt/Frizzled pathway into the vicinity of the
      receptor.

PMID- 12067715
TI  - ARF6: a newly appreciated player in G protein-coupled receptor desensitization.
AB  - The luteinizing hormone/choriogonadotropin hormone receptor (LH/CG R) signals to
      regulate ovulation, corpus luteum formation, and fetal survival during pregnancy.
      Agonist binding to the LH/CG R is poorly reversible, emphasizing the importance
      of a cellular mechanism to temper signaling by a potentially persistently active
      receptor. Like other G protein-coupled receptors (GPCRs), signaling by this
      receptor is modulated by its binding of an arrestin. We have identified ADP
      ribosylation factor 6 (ARF6) as a protein whose activation state is regulated by
      the LH/CG R and which functions to regulate the availability of plasma membrane
      docked arrestin 2 to this receptor. We hypothesize that ARF6 might also serve
      GPCRs other than the LH/CG R to regulate the availability of arrestin 2 for
      receptor desensitization.

PMID- 12067716
TI  - The centrosome cycle.
AB  - The centrosome is the major microtubule-organizing center of animal cells. It
      influences cell shape and polarity and directs the formation of the bipolar
      mitotic spindle. Numerical and structural centrosome aberrations have been
      implicated in disease, notably cancer. In dividing cells, centrosomes need to be
      duplicated and segregated in synchrony with chromosomes. This centrosome cycle
      requires a series of structural and functional transitions that are regulated by
      both phosphorylation and proteolysis. Here we summarize recent information on the
      regulation of the centrosome cycle and its coordination with the chromosomal cell
      cycle.

PMID- 12067717
TI  - Ca-dependent binding of actin to gelsolin.
AB  - Ca(2+) of 0.3-1.0 microM induces both the exposure of tryptic cleavage sites
      within the gelsolin molecule inaccessible in the Ca-free conformation, and
      binding of one actin monomer to the N-terminal half of gelsolin. On the other
      hand, gelsolin-induced enhancement of pyrene actin fluorescence was observed only
      above 50 microM Ca(2+), and a ternary actin/gelsolin complex preformed in 200
      microM Ca(2+) was stable only above 30 microM Ca(2+). These results provide
      direct evidence for Ca-induced transitions from closed to open conformation of
      the gelsolin molecule in the range of 3 x 10(-7) to 10(-6) M Ca(2+). They also
      suggest that Ca(2+)>10(-5) M is required to stabilize actin-actin contacts in the
      2:1 actin/gelsolin complex.

PMID- 12067718
TI  - Identification of a CTL4/Neu1 fusion transcript in a sialidosis patient.
AB  - The deficiency of the lysosomal neuraminidase (NEU1; sialidase) causes the
      storage disorder sialidosis with symptoms ranging from eye abnormalities and
      neurological disturbances to skeletal malformations, mental retardation and early
      death. Sialidosis patients encompassing a wide spectrum of clinical symptoms were
      screened for mutations in neu1. We identified the same homozygous interstitial
      deletion (11 kb) in two patients causing the fusion of exon 10 of CTL4 (New Gene
      22; NG22) with the 3'-UTR of neu1. In one patient we found the resulting
      CTL4/Neu1 fusion transcript, in the other we detected an alternatively spliced
      CTL4 transcript (retention of intron 9).

PMID- 12067719
TI  - Crystal structure of human calmodulin-like protein: insights into its functional
      role.
AB  - A calmodulin (CaM)-like protein (hCLP) is expressed in human mammary epithelial
      cells but appears to be limited to certain epithelial cells such as those found
      in skin, prostate, breast and cervical tissues. A decrease in the expression of
      this protein is associated with the occurrence of tumors in breast epithelium.
      The structure of hCLP determined to 1.5 A resolution by X-ray crystallography
      shows a distinct 30 degrees displacement along the interconnecting central helix,
      when compared to the highly conserved structure of vertebrate CaM, resulting in a
      difference in the relative orientation of its two globular domains. Additionally,
      the electric surface potential landscape at the target protein binding regions on
      the two globular domains of hCLP is significantly different from those of CaM,
      indicating that the respective ranges of hCLP and hCaM target proteins do not
      fully overlap. Observations that hCLP can competitively inhibit CaM activation of
      target proteins also imply a role for hCLP in which it may also serve as a
      modulator of CaM activity in the epithelial cells where hCLP is expressed.

PMID- 12067720
TI  - Circular dichroism spectroscopy of fluorescent proteins.
AB  - Circular dichroism (CD) spectra have been obtained from several variants of green
      fluorescent protein: blue fluorescent protein (BFP), enhanced cyan fluorescent
      protein (CFP), enhanced green fluorescent protein (GFP), enhanced yellow
      fluorescent protein (YFP), all from Aequorea victoria, and the red fluorescent
      protein from the coral species Discosoma (DsRed). We demonstrate that CD spectra
      in the spectral fingerprint region of the chromophore yield spectra that after
      normalization are not coincident with the normalized absorbance spectra of GFP,
      YFP and DsRed. On the other hand, the CD spectra of BFP and CFP coincide with the
      absorbance spectra. The resolution of absorption and CD spectra into Gaussian
      bands confirmed the location of the different electronic band positions of GFP
      and YFP as reported in the literature using other techniques. In the case of BFP
      and CFP the location of Gaussian bands provided information of the vibrational
      progression of the electronic absorption bands. The CD spectrum of DsRed is
      anomalous in the sense that the major CD band has a clear excitonic character.
      Far-UV CD spectra of GFP confirmed the presence of the high beta-sheet content of
      the polypeptide chain in the three-dimensional structure.

PMID- 12067721
TI  - The LIM domain protein Lmo2 binds to AF6, a translocation partner of the MLL
      oncogene.
AB  - The LIM only protein Lmo2 plays an important role in hematopoiesis and
      leukemogenesis. Lmo2 acts as a bridging molecule between components of
      hematopoietic gene regulatory protein complexes. We used the yeast two-hybrid
      system to identify novel Lmo2 interacting proteins and found that the AF6 protein
      binds to Lmo2. AF6 is a recurrent fusion partner of MLL, the human homolog of
      Drosophila trithorax chromatin remodeling protein that is involved in childhood
      leukemia and mixed lineage leukemia. Our data support the notion that recurrent
      fusion partners of chimeric MLL proteins recruit hematopoietic gene regulatory
      complexes.

PMID- 12067722
TI  - Hepatic amino acid-dependent signaling is under the control of AMP-dependent
      protein kinase.
AB  - It has become increasingly clear in recent years that amino acids can stimulate a
      signal transduction pathway resulting in the phosphorylation of mammalian target
      of rapamycin downstream targets. We have now found that amino acid-dependent
      phosphorylation of p70S6 kinase and of S6 in hepatocytes is prevented when AMP
      dependent protein kinase (AMPK) is activated by either the purine ribonucleoside
      analogue AICAriboside, fructose or glycerol. Insulin-dependent phosphorylation of
      protein kinase B is not affected by AMPK activation. Protein synthesis is
      strongly inhibited when AMPK is activated. It is concluded that amino acid
      dependent signaling, a protein-anabolic signal, can be effectively antagonized by
      activation of AMPK.

PMID- 12067723
TI  - Promotion of cathepsin L activity in newt spermatogonial apoptosis induced by
      prolactin.
AB  - We previously showed that prolactin (PRL) induces apoptosis in newt secondary
      spermatogonia and indicated that caspase activity is involved in the apoptosis.
      Since it was recently reported that Z-VAD-fmk, a pan-caspase inhibitor, blocks
      activity of cysteine cathepsins as well, we examined whether cathepsin is
      involved in the newt spermatogonial apoptosis. We found cathepsin L activity in
      the testis that was elevated by PRL in organ culture of testis, while E-64d, a
      lysosomal cysteine protease inhibitor, and Z-VAD-fmk suppressed it and
      chromosomal condensation. These results suggest that cathepsin L activity play a
      pivotal role in PRL-induced spermatogonial apoptosis.

PMID- 12067724
TI  - Bax expression protects yeast plasma membrane against ethanol-induced
      permeabilization.
AB  - The mechanism by which the expression of pro-apoptotic protein Bax is able to
      kill yeast was investigated. Ethanol stress induces a permeabilization of the
      plasma membrane revealed by propidium iodide accumulation. Bax expression,
      although killing yeast cells, prevents this permeabilization. These effects are
      modulated by aeration, by manipulation of the unsaturation index of fatty acids
      and by addition of resveratrol, a known inhibitor of lipid oxidation. These data
      suggest that lipid oxidation is involved in Bax effects. Taken together, these
      data show for the first time a direct effect of Bax on plasma membrane
      permeability properties and suggest that yeast is a powerful tool for
      investigating the molecular mechanisms underlying this process.

PMID- 12067725
TI  - Estrogens prevent calcium-induced release of cytochrome c from heart
      mitochondria.
AB  - We investigated the effect of estrogens on heart mitochondrial functions and
      whether estrogens can prevent calcium-induced release of cytochrome c from
      mitochondria. 10 nM-10 microM 17beta-estradiol or 4-hydroxytamoxifen did not
      affect mitochondrial respiration rate and membrane potential in state 3 and state
      4. Higher concentrations of both agents decreased state 3 respiration rate and
      membrane potential. 100 nM 17beta-estradiol and 4-hydroxytamoxifen blocked high
      calcium-induced cytochrome c release from mitochondria but not mitochondrial
      swelling. Thus, at physiological concentrations estrogens do not affect
      mitochondrial respiratory functions but protect heart mitochondria from high
      calcium-induced release of cytochrome c.

PMID- 12067726
TI  - ERG6 and PDR5 regulate small lipophilic drug accumulation in yeast cells via
      distinct mechanisms.
AB  - Diagnosis and circumvention of multi-drug resistance requires an understanding of
      the underlying cellular mechanisms. In the model organism Saccharomyces
      cerevisiae, deletions of PDR5 or ERG6 increase sensitivity to many small
      lipophilic drugs. Pdr5p is a plasma membrane ATP-binding cassette transporter
      that actively exports drugs, thereby lowering their intracellular levels. The
      mechanism by which ERG6, an enzyme in sterol biosynthesis, affects drug
      accumulation is less clear. We show here that ERG6 limits the rate of passive
      drug diffusion across the membrane, without affecting Pdr5p-mediated drug export.
      Consistent with their action by distinct mechanisms, PDR5 and ERG6 effects on
      drug accumulation are additive.

PMID- 12067727
TI  - Fusion of alphaviruses with liposomes is a non-leaky process.
AB  - It has been reported that low-pH-induced fusion of influenza virus with liposomes
      results in rapid and extensive release of both low- and high-molecular-weight
      substances from the liposomes [Gunther-Ausborn et al., J. Biol. Chem. 270 (1995)
      29279-29285; Shangguan et al., Biochemistry 35 (1996) 4956-4965]. Here, we
      demonstrate retention of encapsulated water-soluble compounds during fusion of
      Semliki Forest virus (SFV) or Sindbis virus with liposomes at low pH. Under
      conditions allowing complete fusion of the liposomes, a limited fluorescence
      dequenching of liposome-encapsulated calcein was observed, particularly for SFV.
      Also, radioactively labeled inulin or sucrose were largely retained. Freezing and
      thawing of the viruses in the absence of sucrose resulted in an enhanced
      leakiness of fusion. These results support the notion that the alphavirus fusion
      event per se is non-leaky and may well involve a discrete hemifusion
      intermediate.

PMID- 12067728
TI  - Targeted disruption of LIG-1 gene results in psoriasiform epidermal hyperplasia.
AB  - The gene encoding a transmembrane glycoprotein LIG-1, of which the extracellular
      region was organized with the leucine-rich repeats and immunoglobulin-like
      domains, was disrupted in mice by gene targeting. LIG-1-deficient mice developed
      a skin change on the tail and facial area after birth. The affected skin was
      histologically reminiscent of the epidermis in human common skin disease
      'psoriasis'. LIG-1 was expressed in basal cells of the epidermis and outer root
      sheath cells of hair follicles in mice. Interestingly, the LIG-1 expression was
      apparently down-regulated in the psoriatic lesions, suggesting that LIG-1
      inversely correlates with proliferative ability of epidermal keratinocytes.

PMID- 12067729
TI  - A point mutation at the subunit interface of hypoxanthine-guanine-xanthine
      phosphoribosyltransferase impairs activity: role of oligomerization in catalysis.
AB  - Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) from Plasmodium
      falciparum catalyzes the phosphoribosylation of hypoxanthine, guanine and
      xanthine. The functionally active form of HGXPRT is a tetramer but interface
      residues do not contribute to catalysis. Here we report the characterization of
      an interface mutant Y96C, which has a decreased k(cat), an increase in the K(m)
      for phosphoribosyl pyrophosphate (PRPP) and no change in K(m) for the purine
      bases when compared to the wild type enzyme. The mutant enzyme does not
      tetramerize in the presence of PRPP, unlike the wild type in which the tetramer
      is stabilized by PRPP. This is the first report of a HGXPRT mutation, at a unique
      interface where non-adjacent subunits interact, that impairs catalysis.

PMID- 12067730
TI  - Effect of protein disulfide isomerase on the rate-determining steps of the
      folding of bovine pancreatic ribonuclease A.
AB  - The effects of protein disulfide isomerase (PDI) on the four structured des
      species that accumulate in the rate-determining steps of ribonuclease A folding
      were investigated at pH 8.0 and 15 degrees C. The results indicate that PDI
      catalyzes the conversion of the kinetically trapped intermediates, des-[26-84]
      and des-[58-110], by reshuffling them into the on-pathway intermediate, des-[40
      95], and the formation of native protein, by acting as both a chaperone and an
      oxidase on this on-pathway intermediate. These results provide the first strong
      evidence for the mechanism of PDI in the rate-determining steps of the oxidative
      folding pathways of ribonuclease A. Our approach, using PDI and blocked PDI,
      combined with the fast-blocking 2-aminoethyl methanethiosulfonate method, may be
      generally applicable to the clarification of the effect of PDI on folding
      intermediates.

PMID- 12067731
TI  - Halocidin: a new antimicrobial peptide from hemocytes of the solitary tunicate,
      Halocynthia aurantium.
AB  - From hemocytes of the tunicate Halocynthia aurantium we purified a new
      antimicrobial peptide named halocidin. The native peptide had a mass of 3443 Da
      and comprised two different subunits containing 18 amino acid residues
      (WLNALLHHGLNCAKGVLA) and 15 residues (ALLHHGLNCAKGVLA), which were linked
      covalently by a single cystine disulfide bond. Two different monomers were
      separately synthesized and used to make three additional isoforms (15 residue
      homodimer, 18 residue homodimer, heterodimer). In antimicrobial assays performed
      with synthetic peptides of halocidin, it was confirmed that congeners of the 18
      residue monomer were more active than those of the 15 residue monomer against
      methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas
      aeruginosa.

PMID- 12067732
TI  - Two novel antifungal peptides distinct with a five-disulfide motif from the bark
      of Eucommia ulmoides Oliv.
AB  - Two antifungal peptides, named EAFP1 and EAFP2, have been purified from the bark
      of Eucommia ulmoides Oliv. Each of the sequences consists of 41 residues with a N
      terminal blockage by pyroglutamic acid determined by automated Edman degradation
      in combination with the tandem mass spectroscopy and the C-terminal ladder
      sequencing analysis. The primary structurs all contain 10 cysteines, which are
      cross-linked to form five disulfide bridges with a pairing pattern (C1-C5, C2-C9,
      C3-C6, C4-C7, C8-C10). This is the first finding of a plant antifungal peptide
      with a five-disulfide motif. EAFP1 and EAFP2 show characteristics of hevein
      domain and exhibit chitin-binding properties similar to the previously identified
      hevein-like peptides. They exhibit relatively broad spectra of antifungal
      activities against eight pathogenic fungi from cotton, wheat, potato, tomato and
      tobacco. The inhibition activity of EAFP1 and EAFP2 can be effective on both
      chitin-containing and chitin-free fungi. The values of IC(50) range from 35 to
      155 microg/ml for EAFP1 and 18 to 109 microg/ml for EAFP2. Their antifungal
      effects are strongly antagonized by calcium ions.

PMID- 12067733
TI  - The vitronectin binding area of plasminogen activator inhibitor-1, mapped by
      mutagenesis and protection against an inactivating organochemical ligand.
AB  - A distinguishing feature of serpins is their ability to undergo a conformational
      change consisting in insertion of the reactive centre loop (RCL) into beta-sheet
      A. In the serpin plasminogen activator inhibitor-1 (PAI-1), RCL movements are
      regulated by vitronectin, having a previously poorly defined binding site lateral
      to PAI-1's beta-sheet A. Using a novel strategy, based on identification of amino
      acid residues necessary for vitronectin protection of PAI-1 against inactivation
      by 4,4'-dianilino-1,1'-bisnaphthyl-5,5'-disulfonic acid, we have defined a
      vitronectin binding surface spanning 10 residues between alpha-helix F, beta
      strand 2A, and alpha-helix E. Our results contribute to elucidating the unique
      serpin conformational change.

PMID- 12067734
TI  - Palindromic repetitive elements in the mitochondrial genome of Volvox.
AB  - Group I introns were found in the cob and cox I genes of Volvox carteri. These
      introns contain tandem arrays of short palindromic sequences that are related to
      each other. Inspection of other regions in the mtDNA revealed that similar
      palindromic repetitive sequences are dispersed in the non-protein coding regions
      of the mitochondrial genome. Analysis of the group I intron in the cob gene of
      another member of Volvocaceae, Volvox aureus, has shown that its sequence is
      highly homologous to its counterpart in V. carteri with the exception of a
      cluster of palindromic sequences not found in V. carteri. This indicates that the
      palindromic clusters were inserted into the introns after divergence of the two
      species, presumably due to frequent insertions of the palindromic elements during
      evolution of the Volvocaceae. Possible involvement of the palindromic repetitive
      elements in the molecular evolution of functional RNAs is discussed.

PMID- 12067735
TI  - ms1, a novel stress-responsive, muscle-specific gene that is up-regulated in the
      early stages of pressure overload-induced left ventricular hypertrophy.
AB  - We have identified and characterised a cDNA encoding a novel gene, designated
      myocyte stress 1 (ms1), that is up-regulated within 1 h in the left ventricle
      following the application of pressure overload by aortic banding in the rat. The
      deduced ms1 protein of 317 amino acids contains several putative functional
      motifs, including a region that is evolutionarily conserved. Distribution
      analysis indicates that rat ms1 mRNA expression is predominantly expressed in
      striated muscle and progressively increases in the left ventricle from embryo to
      adulthood. These findings suggest that ms1 may be important in striated muscle
      biology and the development of pressure-induced left ventricular hypertrophy.

PMID- 12067737
TI  - Identifying genes related to drug anticancer mechanisms using support vector
      machine.
AB  - In an effort to identify genes related to the cell line chemosensitivity and to
      evaluate the functional relationships between genes and anticancer drugs acting
      by the same mechanism, a supervised machine learning approach called support
      vector machine was used to label genes into any of the five predefined anticancer
      drug mechanistic categories. Among dozens of unequivocally categorized genes,
      many were known to be causally related to the drug mechanisms. For example, a few
      genes were found to be involved in the biological process triggered by the drugs
      (e.g. DNA polymerase epsilon was the direct target for the drugs from DNA
      antimetabolites category). DNA repair-related genes were found to be enriched for
      about eight-fold in the resulting gene set relative to the entire gene set. Some
      uncharacterized transcripts might be of interest in future studies. This method
      of correlating the drugs and genes provides a strategy for finding novel
      biologically significant relationships for molecular pharmacology.

PMID- 12067736
TI  - Optimization of GFP levels for analyzing Salmonella gene expression during an
      infection.
AB  - Green fluorescent protein (GFP) is an attractive reporter for Salmonella gene
      expression analysis but might interfere with virulence when expressed at high
      levels. To identify suitable GFP levels, we constructed a series of Salmonella
      strains expressing different amounts of GFP and measured their fluorescence and
      colonization levels in infected mice. The results show that GFP concentrations in
      the range of 7000-200,000 molecules per Salmonella cell are detectable in ex vivo
      samples using flow cytometry, and cause no major Salmonella virulence defect.
      Appropriate GFP levels can be obtained with weak promoters and stable GFP, or
      strong promoters and destabilized GFP.

PMID- 12067738
TI  - Earthworm species of the genus Eisenia can be phenotypically differentiated by
      metabolic profiling.
AB  - The universality of low molecular weight metabolites allows rapid and
      straightforward investigation of the biochemistry of genetically uncharacterised
      species. Thus ex vivo metabolic profiling in combination with multivariate data
      analysis (metabonomics) offers great potential in comparative biology. Here we
      present the first use of high resolution nuclear magnetic resonance (NMR)
      spectroscopy to distinguish closely related animal species via their metabolic
      phenotype (metabotype). We have profiled the three Eisenia (Oligochaeta,
      Lumbricidae) species Eisenia fetida, Eisenia andrei and Eisenia veneta using
      tissue extracts and coelomic fluid analysis. The low molecular weight biochemical
      profiles of tissue extracts were highly conserved for all three species, with E.
      fetida and E. andrei being more similar to each other than to E. veneta. However
      the metabolic profiles of the coelomic fluid of the different species were highly
      distinctive - the NMR spectra allowed unequivocal identification of species.
      Multivariate statistics were also used to quantify these spectral differences and
      to enable simplified graphical visualisation of species similarity. These results
      show that two morphologically undistinguishable species (E. fetida and E. andrei)
      differ markedly in their biochemical profiles despite apparently occupying the
      same ecological niche, and indicate that metabolic phenotype profiling can be
      used as a powerful functional genomics tool.

PMID- 12067739
TI  - Myosin II from rabbit skeletal muscle and Dictyostelium discoideum and its
      interaction with F-actin studied by (1)H NMR spectroscopy.
AB  - Mg-F-actin occurs in two conformational states, I and M, where the N-terminal
      amino acids are either immobile or highly mobile. In the rigor or ADP complex of
      rabbit myosin S1 with Mg-F-actin the N-terminal acetyl group of actin stays in
      its highly mobile state. The same is true for the complexes with the myosin motor
      domain from Dictyostelium discoideum. This excludes a direct strong interaction
      of the N-terminal amino acids with myosin in the rigor state as suggested. An
      interaction of the N-terminus of F-actin with myosin is also not promoted by
      occupying its low-affinity binding site(s) with divalent ions. The N-terminal
      high-mobility region may be part of a structural system which has evolved for
      releasing inadequate stress applied to the actin filaments.

PMID- 12067740
TI  - 2',3'-Dialdehydo-UDP-N-acetylglucosamine inhibits UDP-N-acetylglucosamine 2
      epimerase, the key enzyme of sialic acid biosynthesis.
AB  - Sialic acids comprise a family of terminal sugars essential for a variety of
      biological recognition systems. UDP-N-acetylglucosamine 2-epimerase catalyzes the
      first step of their biosynthesis. Periodate-oxidized UDP-N-acetylglucosamine,
      namely 2',3'-dialdehydo-UDP-alpha-D-N-acetylglucosamine, was found to be an
      effective inhibitor of this enzyme, compared with the periodate oxidation
      products of compounds such as UDP, uridine or methyl riboside. It bound
      covalently to amino acids in the active site causing an irreversible inhibition.
      This compound may therefore represent a basis for the synthesis of potent
      inhibitors of UDP-N-acetylglucosamine 2-epimerase and, as a consequence, of the
      biosynthesis of sialic acids.

PMID- 12067741
TI  - Molecular dynamics simulations revealed Ca(2+)-dependent conformational change of
      Calmodulin.
AB  - Molecular dynamics simulations were performed to simulate Ca(2+)-dependent
      conformational change of calmodulin (CaM). Simulations of the fully Ca(2+)-bound
      form of CaM (Holo-CaM) and the Ca(2+)-free form (Apo-CaM) were performed in
      solution for 4 ns starting from the X-ray crystal structure of Holo-CaM. A
      striking difference was observed between the trajectories of Holo-CaM and Apo
      CaM: the central helix remained straight in the former but became largely bent in
      the latter. Also, the flexibility of Apo-CaM was higher than that of Holo-CaM.
      The results indicated that the bound Ca(2+) ions harden the structure of CaM.

PMID- 12067742
TI  - Human substance P receptor undergoes agonist-dependent phosphorylation by G
      protein-coupled receptor kinase 5 in vitro.
AB  - G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied G
      protein-coupled receptors, leading to receptor desensitization. Seven GRKs,
      designated GRK1 through 7, have been characterized. GRK5 is negatively regulated
      by protein kinase C. We investigated whether human substance P receptor (hSPR) is
      a substrate of GRK5. We report that membrane-bound hSPR is phosphorylated by
      purified GRK5, and that both the rate and extent of phosphorylation increase
      dramatically in the presence of substance P. The phosphorylation has a high
      stoichiometry (20+/-4 mol phosphate/mol hSPR) and a low K(m) (1.7+/-0.1 nM).
      These data provide the first evidence that hSPR is a substrate of GRK5.

PMID- 12067743
TI  - Cerebral processes involved in reading as a function of the structure of various
      writing systems.

PMID- 12067745
TI  - Neuroanatomy and neurophysiology in schizophrenia.
AB  - Schizophrenia is a major mental disorder, characterized by their set of symptoms,
      including hallucinatory-delusional symptoms, thought disorder, emotional
      flattening, and social withdrawal. Since 1980s, advances in neuroimaging and
      neurophysiological techniques have provided tremendous merits for investigations
      into schizophrenia as a brain disorder. In this article, we first overviewed
      neuroanatomical studies using structural magnetic resonance imaging (s-MRI), MR
      spectroscopy (MRS), and postmortem brains, followed by neurophysiological studies
      using event-related potentials (ERPs) and magnetoencephalography (MEG), in
      patients with schizophrenia. Evidences from these studies suggest that
      schizophrenia is a chronic brain disorder, structurally and functionally
      affecting various cortical and subcortical regions involved in cognitive,
      emotional, and motivational aspects of human behavior. Second, we reviewed recent
      investigations into neurobiological basis for schizophrenic symptoms (auditory
      hallucinations and thought disorder) using these indices as well as hemodynamic
      assessments such as positron emission tomography (PET) and functional MRI (f
      MRI). Finally, we addressed the issue of the heterogeneity of schizophrenia from
      the neurobiological perspective, in relation to the neuroanatomical and
      neurophysiological measures.

PMID- 12067746
TI  - Functional significance of the cortico-subthalamo-pallidal 'hyperdirect' pathway.
AB  - How the motor-related cortical areas modulate the activity of the output nuclei
      of the basal ganglia is an important issue for understanding the mechanisms of
      motor control by the basal ganglia. The cortico-subthalamo-pallidal 'hyperdirect'
      pathway conveys powerful excitatory effects from the motor-related cortical areas
      to the globus pallidus, bypassing the striatum, with shorter conduction time than
      effects conveyed through the striatum. We emphasize the functional significance
      of the 'hyperdirect' pathway and propose a dynamic 'center-surround model' of
      basal ganglia function in the control of voluntary limb movements. When a
      voluntary movement is about to be initiated by cortical mechanisms, a corollary
      signal conveyed through the cortico-subthalamo-pallidal 'hyperdirect' pathway
      first inhibits large areas of the thalamus and cerebral cortex that are related
      to both the selected motor program and other competing programs. Then, another
      corollary signal through the cortico-striato-pallidal 'direct' pathway
      disinhibits their targets and releases only the selected motor program. Finally,
      the third corollary signal possibly through the cortico-striato-external pallido
      subthalamo-internal pallidal 'indirect' pathway inhibits their targets
      extensively. Through this sequential information processing, only the selected
      motor program is initiated, executed and terminated at the selected timing,
      whereas other competing programs are canceled.

PMID- 12067747
TI  - Blockade of ionotropic receptor responses by progesterone in the ganglion cells
      of Aplysia.
AB  - To compare nongenomic effects of progesterone on various receptor responses of
      neurons, Aplysia ganglion cells were pretreated with 30 microM progesterone for 5
      min and various receptor responses were tested using a conventional voltage-clamp
      method. Progesterone reduced nicotinic receptor-activated Na(+)-currents,
      nicotinic receptor-activated Cl(-)-currents, gamma-aminobutyric acid receptor
      activated Cl(-)-currents, and dopamine receptor-activated Na(+)-currents. These
      depressant effects are similar at two different agonist concentrations. On the
      other hand, progesterone affected neither muscarinic receptor-activated K(+)
      currents nor dopamine receptor-activated K(+)-currents. The former four types of
      receptors are known to be ionotropic while the latter two types of receptors are
      known to be metabotropic. Therefore, progesterone selectively inhibited all the
      types of ionotropic receptor responses, presumably in a noncompetitive manner.

PMID- 12067748
TI  - Effects of cerebrovascular challenges on plasma endothelin.
AB  - Plasma endothelin elevations have been associated with cerebrovascular pathology.
      Mechanisms of stimulation, however, are unknown. Therefore, in healthy subjects a
      marked physiological cerebrovascular response was experimentally provoked by
      hypercapnia, hypocapnia, and alternating capneic conditions. During these
      challenges plasma immunoreactive-endothelin-1 (ir-ET-1) concentrations were
      determined using a radioimmunassay. Physiological effects were continuously
      recorded for pCO(2), cerebral blood flow velocity, pulse frequency, and arterial
      blood pressure. No alterations in plasma ET-1 levels were found upon any of the
      cerebrovascular stimuli. We conclude that massive cerebrovascular challenges in
      healthy individuals do not lead to high circulating ET-1 levels.

PMID- 12067749
TI  - Rapid structural remodeling of shaft synapses associated with long-term
      potentiation in the cat superior cervical ganglion in situ.
AB  - Synaptic plasticity associated with long-term potentiation was studied
      electrophysiologically and ultrastructurally in the cat superior cervical
      ganglion in situ. The preganglionic nerve fiber was stimulated at 10 Hz for 50 s
      for conditioning and then at 1 Hz for 1-3 h to monitor changes in the
      postganglionic compound action potential (PGP). The present material has shown
      the long-term potentiation (LTP), around 120% of the control, which lasted for up
      to 3 h. Fifteen of 18 ganglia (83%) have shown LTP. Ultrastructural studies
      demonstrated the synaptic structural remodeling: (1) The preganglionic nerve
      terminals ordinarily made mainly asymmetrical type of shaft synapses directly
      with dendrites of the ganglion cells that lacked dendritic spines; (2)
      conditioning tetanus rapidly remodeled simple shaft synapses into perforated ones
      characterized by perforations in the postsynaptic density (PSD), some of which
      had synaptic spinules associated with the perforated PSDs, i.e. spinule-synapses;
      (3) a rapid increase in the number of both structures was detected immediately
      after the tetanus. Perforated synapses and the spinule-synapses increased from 5%
      and 0% in the control to 27 and 9% at 0 min, respectively. Spinule-synapses
      occurred about one-third of the perforated shaft synapses; (4) Increased numbers
      of restructured shaft synapses was maintained for 15 min in ganglia expressing
      LTP; (5) Remodeled synapses did not increase in ganglia that did not express LTP
      or ganglia that were activated at 0.5 or 1 Hz. It was suggested a rapid increase
      in the number of remodeled synapses associated with the onset of LTP and its
      durability at its earlier phases in the cat SCG.

PMID- 12067750
TI  - Sex difference in the expression and regulation of nitric oxide synthase gene in
      the rat preoptic area.
AB  - Neuronal nitric oxide synthase (nNOS) mRNA-positive cells were visualized by non
      isotopic in situ hybridization histochemistry in the organum vasculosum of the
      lamina terminalis (OVLT) and the preoptic area (POA) in gonadectomized juvenile
      female and male rats. In the rostral POA (rPOA) at the level of the anteroventral
      periventricular nucleus, nNOS mRNA-positive cells were distributed in an inverted
      V-shaped area over the third ventricle and were in close proximity to cell bodies
      of gonadotropin-releasing hormone (GnRH)-immunoreactive neurons. In the caudal
      POA (cPOA) at the level of the medial preoptic nucleus, no topological
      association existed between GnRH and nNOS. Throughout the rPOA, both the number
      and the area of nNOS mRNA positive cells were significantly larger in the
      gonadectomized females than in the gonadectomized males. Treatment with estradiol
      for 2 days, followed by progesterone in the next morning, which caused an
      increase in serum luteinizing hormone 6 h later, induced a significant reduction
      of the nNOS mRNA expression in the rPOA in the female but not in the male rat at
      the time of sacrifice. In the OVLT and the cPOA, ovarian steroids had no effect
      on nNOS mRNA expression of both sexes. The results indicate that nNOS mRNA
      expression in the rPOA is sexually dimorphic and regulated by ovarian steroids in
      a sex specific manner.

PMID- 12067751
TI  - Critical spectral regions for vowel identification.
AB  - The first two formant frequencies (F1 and F2) are the cues important for vowel
      identification. In the categorization of the naturally spoken vowels, however,
      there are overlaps among the vowels in the F1 and F2 plane. The fundamental
      frequency (F0), the third formant frequency (F3) and the spectral envelope have
      been proposed as additional cues. In the present study, to investigate the
      spectral regions essential for the vowel identification, untrained subjects
      performed the forced-choice identification task in response to Japanese isolated
      vowels (/a, o, u, e, i/), in which some spectral regions were deleted. Minimum
      spectral regions needed for correct vowel identification were the two regions
      including F1 and F2 (the first and fourth in the quadrisected F1-F2 regions in
      Bark scale). This was true even when phonetically different vowels had a similar
      combination of F1 and F2 frequency components. F0 and F3 cues were not
      necessarily needed. It is concluded that the relative importance in the spectral
      region is not equivalent, but weighted on the two critical spectral regions. The
      auditory system may identify the vowels by analyzing the information of the
      spectral shapes and the formant frequencies (F1 and F2) in these critical
      spectral regions.

PMID- 12067752
TI  - Effect of lesions in the lateral nucleus of the amygdala on fear conditioning
      using auditory and visual conditioned stimuli in rats.
AB  - The lateral nucleus of the amygdala (LA) is believed to be the site of auditory
      conditioned stimulus (CS) relay in classical fear conditioning. The present study
      attempts to determine whether the LA is specifically involved in fear
      conditioning using an auditory CS. Seven rats with lesions in the LA (Tone
      Lateral group) and eight sham-operated rats in the control group were trained
      using an auditory CS (overtone based on an 800 Hz fundamental tone, 70 dB, 3.7 s)
      paired with foot shock (1.0 mA, 0.5 s). Five rats with lesions in the LA (Light
      Lateral group) and eight unoperated rats in the control group were trained using
      a visual CS (25 W light, 3.7 s). The behavioral index of fear conditioning was a
      potentiation of the startle reflex in the presence of CS. All rats in the control
      group and Light-Lateral group showed this potentiation, whereas those in the Tone
      Lateral group did not. These results suggest that the LA is an input site of
      auditory CS information into the amygdala, and that it is not a site of visual CS
      information input in fear conditioning. Thus, each modality of CS may have a
      specific subnucleus of the amygdala that mediates fear conditioning.

PMID- 12067753
TI  - Lowered response threshold and increased responsiveness to mechanical stimulation
      of cutaneous nociceptive fibers in streptozotocin-diabetic rat skin in vitro-
      correlates of mechanical allodynia and hyperalgesia observed in the early stage
      of diabetes.
AB  - Rats rendered diabetic by streptozotocin (STZ) show allodynia and hyperalgesia
      and thus, have been offered as a model of pain in diabetic neuropathy. However,
      recent electrophysiological studies on these rats found that C-fiber nociceptors
      were not consistently hyperexcitable to mechanical stimulations by von Frey hairs
      and that there was no change in their response thresholds. In the present study,
      we used rat skin-saphenous nerve in vitro preparations, in which the receptive
      fields of identified single C-polymodal receptors (CPRs) can be accurately
      stimulated with a servo-controlled mechanical stimulator. Single fiber recordings
      from CPRs were performed in diabetic rats with an increased behavioral
      nociceptive response 7-19 days after STZ injection. The proportion of units with
      spontaneous activity and the magnitude of this activity increased in the diabetic
      preparations. The response thresholds of CPRs were significantly decreased with
      ramp-pressure stimulation and their response magnitude to the suprathreshold
      stimulation was significantly increased in diabetic rats. In addition, the
      response pattern to mechanical stimulation was also changed to a non-adapting
      type. These findings suggest that changes in CPRs contribute to the enhanced
      nociception observed in the early stage of diabetic neuropathy.

PMID- 12067754
TI  - Angiotensin II-induced inhibition of calcium currents via G(q/11)-protein
      involving protein kinase C in hamster submandibular ganglion neurons.
AB  - Angiotensin II (AngII) is one of the most important vasoconstrictive hormones but
      is also known to act as a neuromodulator and a neurotransmitter in the central
      and peripheral nervous systems. In a previous study, we have shown that AngII,
      mediated by AT(1) receptors, inhibits voltage-dependent calcium channel (VDCC)
      currents (I(Ca)) via G-proteins in submandibular ganglion (SMG) neurons. In this
      study, we further characterized the signal transduction of AngII-induced
      inhibition of I(Ca). Application of 1 microM AngII inhibited I(Ca) by 32.1+/-2.7%
      (mean+/-S.E.M., n=9). Intracellular dialysis of anti-G(q/11) antibodies
      attenuated these inhibition (8.8+/-1.3%, n=6). In addition, treatment of protein
      kinase C (PKC) activator and inhibitor also attenuated these inhibition (8.0+/
      0.9 and 9.8+/-0.9%, n=6 and 9, respectively). We therefore conclude that AngII
      inhibits VDCC via G(q/11)-proteins involving in SMG neurons. In addition, such
      PKC-dependent pathways mediated mainly L-type VDCC inhibition.

PMID- 12067755
TI  - Antibodies to B7.1 define the GFCC'C" face of the N-terminal domain as critical
      for co-stimulatory interactions.
AB  - Antagonists of the B7 family of co-stimulatory molecules have the potential for
      altering immune responses therapeutically. To better define the requirements for
      such inhibitors, we have mapped the binding of an entire panel of blocking
      antibodies specific for human B7.1. By mutagenesis, each of the residues critical
      for blocking antibody binding appeared to fall entirely within the N-terminal V
      set domain of B7.1. Thus, although antibody-antigen interacting surfaces can be
      quite large, these results indicate that a relatively small portion of the
      GFCC'C" face of this domain is crucial for further antagonist development.

PMID- 12067756
TI  - Regulation of TNF-alpha-mediated hyperplasia through TNF receptors, TRAFs, and NF
      kappaB in synoviocytes obtained from patients with rheumatoid arthritis.
AB  - Although the etiology of rheumatoid arthritis (RA) has not been clearly
      understood to date, the hyperplasia of the synovial membrane imposed by pro
      inflammatory cytokines has been suggested to play a crucial role in the
      progression of this disease. TNF-alpha, a potent pro-inflammatory cytokine, was
      detected at highly enhanced concentrations in the blood and synovial fluids of
      patients with RA relative to those of patients with osteoarthritis and normal
      subjects. To evaluate the role of TNF-alpha in the synovial hyperplasia during
      the pathogenic state, we investigated cellular outcomes and molecular mechanisms
      of synoviocytes in response to TNF-alpha. Following TNF-alpha treatment,
      fibroblast-like synoviocytes (FLS) obtained from patients with RA proliferated,
      unlike the cells from a normal subject that were unaffected. This TNF-alpha
      induced proliferation of synoviocytes obtained from RA patients coincided with
      down-regulation of TNFR1 and up-regulation of TNFR2 and TRAF1-6, as well as NF
      kappaB activation. TNF-alpha-induced proliferation of synoviocytes was inhibited
      by transfection with a dominant negative mutant form of I-kappaBalpha cDNA (I
      kappaBalphadN). Moreover, following TNF-alpha treatment, transfectants with I
      kappaBalphadN underwent apoptosis, whereas mock-transfectants did not. Taken
      together, these results suggest that high levels of TNF-alpha present in RA
      synovium play an important role in the synovial hyperplasia of RA by suppressing
      apoptosis and promoting proliferation of synoviocytes through NF-kappaB-dependent
      signaling pathways mediated by up-regulated TNFR2 and TRAF1-6 molecules.

PMID- 12067757
TI  - Role for complement receptors (CD21/CD35) in the regulation of recombination
      activating gene expression in murine peripheral B cells.
AB  - A population of peripheral B cells have been shown to express recombination
      activating gene products, RAG-1 and RAG-2, which are considered to be involved in
      revising the B cell antigen receptor (BCR) in the periphery. BCR engagement has
      been reported to turn off RAG expression in peripheral B cells, whereas the same
      treatment has an opposite effect on immature B cells in the bone marrow. In
      contrast to receptor editing that is involved in the removal of autoreactivity in
      immature B cells, it has been shown that secondary V(D)J rearrangement in
      peripheral B cells, termed receptor revision, contributes to affinity maturation
      of antibodies. Here, we show that RAG-2 expression in murine splenic B cells was
      abrogated by the coligation of BCR with complement receptors (CD21/CD35) much
      more efficiently than by the engagement of BCR alone. On the other hand, the same
      coligation augmented proliferation of anti-CD40-stimulated B cells. These
      findings suggest a crucial role for CD21/CD35 in directing the conservation or
      the revision of BCRs in peripheral B cells.

PMID- 12067758
TI  - Dendritomas formed by fusion of mature dendritic cells with allogenic human
      hepatocellular carcinoma cells activate autologous cytotoxic T lymphocytes.
AB  - Mature dendritic cells (DCs) have highly expressed CD1a, MHC class I, MHC class
      II, B7-1, B7-2 and ICAM-I molecules, all of which are essential for activation of
      naive T cells. In this study, dendritomas were formed by fusion of hepatocellular
      carcinoma (HCC) SMMC-7721 cells with autologous DCs in vitro. DCs were obtained
      from adherent monocytes cultured in the presence of GM-CSF and IL-4 and were
      matured in monocyte-conditioned media. Expression of MHC class II and HCC
      specific antigen by these dendritomas were determined using a specific murine
      anti-HCC monoclonal antibody (mAb) specific for HCC cell line SMMC-7721, and a
      murine anti-human HLA-DR mAb, and was also confirmed using bi-dimensional flow
      cytometry and immuno-histostaining. Dendritomas were co-cultured with autologous
      T cells, resulting in activation of T cell proliferation and priming of naive T
      cells to induce MHC class I restricted lysis of HCC SMMC-7721 cells. The results
      imply that these dendritomas may have potential for use in HCC immunotherapy.

PMID- 12067759
TI  - Co-expression of the CD8 receptor in a human CD4+ T-cell clone influences
      proliferation, cytosolic Ca2+ release and cytokine production.
AB  - In normal human subjects a small proportion of peripheral blood T-cells
      simultaneously express both CD4 and CD8 differentiation antigens. In this study
      we characterized a subset of CD4+ clones, from a healthy donor, that is specific
      for the thyrotropin receptor (TSHR) and that showed cells co-expressing the CD8
      receptor. To address whether the expression of the CD8 receptor on the cell
      membrane was associated to differences in the physiology of the T-cells, we
      isolated, from the same clone, CD4 single positive (SP) cells from those co
      expressing CD4/CD8 receptors (DP cells) and stimulated them in vitro with antigen
      presenting cells (APC) carrying TSHR. The results demonstrated that CD8 co
      expression has a profound effect on the physiology of T helper (Th) cells. In
      comparison to cells expressing the CD4 receptor alone, DP T-cells showed: (1)
      increased proliferation; (2) higher and more sustained release of free Ca2+ in
      the cytosol, under stimulus; (3) lower levels of IL-2 and IL-4 released in the
      supernatants; (4) increased amounts of IFN-gamma released.

PMID- 12067761
TI  - Hyperbaric oxygen exposure temporarily reduces Mac-1 mediated functions of human
      neutrophils.
AB  - Highly elevated partial pressures of oxygen achievable during hyperbaric
      oxygenation (HBO) have been shown to reduce leukocyte sequestration following
      ischemia/reperfusion injury suggesting a clinical role for HBO in treatment of
      various disease states characterized by transient ischemia. Previous studies have
      suggested that this effect may be due to inhibition of beta2-integrin function.
      In this study the effect of HBO on various CD11b/CD18 (Mac-1) mediated neutrophil
      functions was investigated in healthy human subjects. HBO 3.0 ATA, 23 m reduced
      adhesion 50% at 2 h with return to pre-HBO levels by 6 h. Homotypic aggregation,
      a Mac-1 dependent function, under fluid shear following stimulation with f-MLP
      was reduced from 20+/-2.6 to 3.4+/-1.0% 2 h after HBO. However, HBO did not
      inhibit adhesion to IL-1beta stimulated HUVEC. Mac-1 mediated oxidative burst
      induced by opsonized zymosan was reduced 38.2+/-10.6% (P<0.05) by HBO. However,
      oxidative burst induced by PMA or f-MLP was not affected. HBO did not alter the
      distribution of neutrophils displaying morphologies associated with stimulation
      (ruffled, bipolar, uropod) over a 24 h period after HBO nor did HBO change the
      percentages of mature versus immature cells. Taken together these findings
      demonstrate that HBO specifically inhibits Mac-1 mediated functions.

PMID- 12067760
TI  - Donor-specific blood transfusion prolongs cardiac allograft survival in rats by
      low nitric oxide production and elevated serum levels of prostaglandin E(2).
AB  - Donor-specific blood transfusion (DST) improves allograft survival, although the
      exact mechanism(s) is not completely understood. The purpose of this study was to
      determine the role of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) in DST
      protective effects, using a rat cardiac transplantation model. Lewis rats (RT
      1(1)) were transfused with fully allogeneic ACI rats (RT-l(a)) blood (DST group)
      or Lewis syngeneic blood (ST) through the portal vein 7 days prior to allogeneic
      cardiac transplantation. Posttransplantation, aminoguanidine (AG)-treated rat
      received continuous intravenous infusion of AG, an inhibitor of inducible nitric
      oxide synthase (iNOS). The survival times of grafted hearts were 5.7+/-0.5, 6.8+/
      0.8 and 9.2+/-1.2 days in ST, ST/AG, and DST groups (n=6 for each group),
      respectively. Inhibition of iNOS in ST/AG group prolonged allograft survival, but
      it was shorter than that in DST rats. Serum nitrite/nitrate levels on
      postgrafting day 5 were significantly higher in ST than in ST/AG and DST groups,
      but were similar in ST/AG and DST groups. These results were confirmed by
      immunohistochemical staining with anti-iNOS antibody. Serum PGE(2) concentrations
      in DST rats were significantly higher than in ST and ST/AG groups. Our results
      suggest that DST prolongs graft survival by enhanced production of PGE(2) with a
      resultant suppression of immune activation. In addition, DST-induced prolongation
      of graft survival may be partially mediated by NO suppression.

PMID- 12067762
TI  - Regulation of NK cell function in vivo by the dose of tumour transplanted in the
      peritoneum.
AB  - Antigen dose is known to regulate T cell activation and anergy. Similarly, dose
      of antigen also regulates NK cell lytic potential and phenotype development.
      Resident peritoneal cells of rat contain a small population of NK and NKT cells.
      Inoculation of AK-5 tumour cells intraperitoneally modulate the cytotoxic
      function of NK and NKT cells present in the peritoneal exudate cells (PEC) in a
      dose dependent manner. Low dose of tumour causes activation of NK and NKT cell
      cytotoxic function and enhanced NK and NKT cell population in PEC, whereas, high
      doses of tumour cause inactivation of NK and NKT cell cytotoxic function and
      depletion of the two sub-populations in the peritoneum. Different doses of tumour
      inoculation in the peritoneal cavity did not suppress the cytotoxic function of
      NK cells from spleen suggesting that a direct interaction between NK cells and
      tumour cells is required for the suppression of NK cell cytotoxic function.
      Tumour inoculation induced secretion of IL-2, IL-12, IFN-gamma and TNF-alpha by
      tumour infiltrating mononuclear cells (TIM) in ascitic fluid as well as in serum.
      The levels of IL-2, IL-12, IFN-gamma and TNF-alpha secretion were higher in
      animals, which rejected tumours as compared with the animals that failed to
      reject the tumours. Injection of anti IL-12 and anti IFN-gamma antibody reduced
      the survival rate of tumour injected animals, however, anti IL-2 antibody had no
      effect on the survival of animals. Following incubation with AK-5 tumour cells,
      activated NK cells upregulated perform expression, whereas, there was
      upregulation of CD95 expression in inactivated NK cells.

PMID- 12067763
TI  - Clustering of a lipid-raft associated pool of ERM proteins at the immunological
      synapse upon T cell receptor or CD28 ligation.
AB  - Although ezrin is tyrosine phosphorylated following TCR ligation, its biological
      role in T cell activation is not known. Here, we shhow that ezrin clusters at the
      immunological synapse upon T cell stimulation. Clustering of ezrin can be
      triggered by TCR ligation, or, more efficiently, by CD28 ligation. The clusters
      of ezrin at the immunological synapse include serine/threonine phosphorylated
      ezrin predominantly located within cell membrane lipid rafts. Based on these
      data, we propose that ezrin may play a role in the formation/stabilization of
      lipid raft signalosomes at the immunological synapse and therefore contribute to
      sustain TCR-dependent signalling.

PMID- 12067764
TI  - Acquired lactose intolerance: a seldom considered cause of diarrhea in the
      palliative care setting.

PMID- 12067765
TI  - Pilot dose finding study of intranasal sufentanil for breakthrough and incident
      cancer-associated pain.

PMID- 12067766
TI  - Re: Uncertainty and opposition of medical students toward assisted death
      practices.

PMID- 12067768
TI  - Opioids causing peripheral edema.

PMID- 12067769
TI  - Validation of the palliative performance scale for inpatients admitted to a
      palliative care unit in Sydney, Australia.

PMID- 12067770
TI  - A scale for measuring patient perceptions of the quality of end-of-life care and
      satisfaction with treatment: the reliability and validity of QUEST.
AB  - We report on the adaptation and evaluation of a previously developed patient
      centered instrument that we call the Quality of End-of-life care and Satisfaction
      with Treatment (QUEST) scale. In a separate group of 30 inpatients, test-retest
      reliability for QUEST items ranged from 63% agreement (kappa = 0.43) to 93%
      agreement (kappa = 0.86) and construct validity was evidenced by correlations
      with a somewhat related satisfaction scale ranging from 0.38 to 0.47. QUEST was
      then administered to 206 consecutive medical inpatients (or their surrogates)
      with DNR orders and to a comparison group of 51 medical inpatients without DNR
      orders at 2 academic medical centers. Among these main study patients, internal
      consistency was reflected by Cronbach alphas of 0.88 to 0.93. QUEST scores showed
      modest inverse correlations with severity of symptoms, but were uncorrelated with
      severity of illness, anxiety, or depression, suggesting an appropriate
      relationship to symptom control but divergence of the underlying construct from
      degree of physical illness or affective state. QUEST scores were lower for
      patients with DNR orders compared to those without DNR orders (P = 0.02 to 0.06).
      Surrogate ratings of satisfaction and quality were uncorrelated with patient
      ratings. Although preliminary, these findings suggest that QUEST may be useful in
      assessing quality and satisfaction with the care rendered by physicians and
      nurses to hospitalized patients at the end of life.

PMID- 12067771
TI  - What is palliative care in Germany? Results from a representative survey.
AB  - The recent development of palliative care inpatient units in Germany has been
      impressive. As a first step for quality assurance, a core documentation form was
      developed in 1996. The core documentation form consisted of 4 pages with 35 items
      documenting physical and psychosocial symptoms at the time of admission,
      diagnostic and therapeutic procedures before and during inpatient treatment, and
      outcome of physical and psychosocial dimensions. Checklists were used for most
      items and free text entries could be added. Of the 65 palliative inpatient units
      in Germany, 44 participated in the second phase of the evaluation of the core
      documentation in 2000. Eight units were affiliated with anesthesiology
      departments, 31 with internal medicine, two with radiotherapy, 1 with a surgical
      department, and 2 units were not affiliated with a department of the hospital. A
      total of 1087 patients were assessed in the 44 units during a period of up to 3
      months. There was a high variability between units in all checklist items of the
      core documentation. Compared to units affiliated with internal medicine
      departments, units affiliated with anesthesiology departments performed less
      chemotherapy, but more immunotherapy; gave fewer infusions and blood transfusions
      but more skin and wound care, and more lymphatic drainage and massage; and
      documented psychosocial interventions more frequently for patients as well as for
      relatives. In one-third of the patients, a consent for omission of therapeutic
      options was documented. Inpatient treatment ended with the death of the patient
      in 45.3% of patients and with discharge in 51.6% (not documented 3.1%). The
      efficacy of inpatient treatment was rated very high by the staff. In conclusion,
      we found large variation in the documentation pertaining to palliative care
      patients at the time of admission, as well as for inpatient treatment, among
      palliative care units in Germany. This was related to the affiliation of the
      units at least to some degree, but also to differences in interests and
      documentation discipline. We suggest that training procedures for documentation
      should be included in crossectional surveys, as the results may not be comparable
      otherwise. However, common documentation instruments may be the first step
      towards an interdisciplinary discussion on aims and methods in palliative care.

PMID- 12067772
TI  - Prevalence and screening of dyspnea interfering with daily life activities in
      ambulatory patients with advanced lung cancer.
AB  - This study aimed to identify 1) the prevalence of "clinical dyspnea," defined
      here as dyspnea interfering with any daily life activities, 2) the impact of
      dyspnea on daily life activities, and 3) the screening ability of the Cancer
      Dyspnea Scale (CDS) and the Dyspnea Numeric Scale (DNS). A total of 157
      outpatients with advanced lung cancer completed the two scales (CDS and DNS)
      along with a questionnaire about interference with daily life activities (normal
      work, walking, sleep, mood, relation with other people, enjoyment of life, and
      general activities). Over half of this population (55%) experienced "clinical
      dyspnea." Dyspnea interfered with not only physical domain (52%), such as walking
      and work, but also with psychological domain (23%), such as mood and enjoyment.
      Both scales were feasible for screening of clinical dyspnea. Applying a screening
      protocol may contribute to avoiding underestimation of clinical dyspnea and lead
      to appropriate interventions for it.

PMID- 12067773
TI  - Factors correlated with dyspnea in advanced lung cancer patients: organic causes
      and what else?
AB  - This study aimed to investigate factors correlated with dyspnea in cancer
      patients among a broad range of medico-psycho-social factors. A total of 171
      consecutive outpatients with advanced lung cancer were recruited. Dyspnea was
      evaluated by using the Cancer Dyspnea Scale, a valid, reliable 12-item self
      rating scale developed to assess the multidimensional nature of dyspnea in cancer
      patients. Possible correlates, including 1) medical (clinical stage, Performance
      Status, SpO(2), organic causes of dyspnea, other symptoms, such as cough and
      pain, etc.), 2) psychological (anxiety and depression), and 3) social (education,
      marital status, existence of confidants, etc.), factors were collected from
      medical charts, interviews, and self-rating questionnaires. Multiple regression
      analysis revealed that psychological distress, presence of organic causes, cough,
      and pain were significantly correlated with dyspnea (P < 0.05, multiple R(2) =
      0.303). The present study confirms that dyspnea is multifactorial and that a
      beneficial therapeutic strategy might include intervention for psychological
      distress and pain.

PMID- 12067774
TI  - Prevalence and treatment of menopausal symptoms among breast cancer survivors.
AB  - Women diagnosed with breast cancer often experience early menopause secondary to
      treatment effects, yet physicians may be reluctant to prescribe hormone
      replacement therapy (HRT) because of the potential increased risk of recurrence.
      To assess the burden of menopausal symptoms, HRT use, and alternative treatments
      in recent breast cancer survivors, a population-based, case-control study was
      conducted among breast cancer survivors and age-matched controls. Wisconsin women
      18-69 years old with a new diagnosis of breast cancer 8-11 months prior to
      interview (n = 110) and control subjects randomly selected from population lists
      (n = 73) responded to a standardized telephone questionnaire that elicited
      information on menopausal symptoms, estrogen and alternative therapies
      (prescription medications, vitamins, herbal preparations, soy products,
      acupuncture, chiropractic) used to alleviate symptoms. We used multivariate
      logistic regression to obtain odds ratios and 95% confidence intervals (CI) for
      symptoms of menopause, use of estrogen, and use of alternative therapies. Breast
      cancer survivors were 5.3 (95% CI 2.7-10.2) times more likely to experience
      symptoms, 25 (95% CI 8.3-100) times less likely to use estrogen, and 7.4 (95% CI
      2.5-21.9) times more likely to use alternatives than controls. Soy, vitamin E,
      and herbal remedies were the most common alternative therapies reported by
      participants; use was greater in cases compared to controls. Most soy users
      reported increasing soy products specifically to reduce the chances of a
      diagnosis of recurrent breast cancer. Among cases, tamoxifen users (n = 62)
      reported a higher prevalence of symptoms and a higher prevalence of alternative
      treatments. This is the first population-based survey of menopausal symptoms and
      treatments that compares breast cancer cases with disease-free controls. Cases
      are both more likely to experience menopausal symptoms and less likely to use HRT
      than controls. Instead, cases treat menopausal symptoms with vitamin E and soy
      products, even though the safety and efficacy of these therapies are unproven.
      The increased use of soy products in this population has not been previously
      documented.

PMID- 12067775
TI  - Clinical applications for change-point analysis of herpes zoster pain.
AB  - Pain is the most frequent and disabling complication of herpes zoster. The
      analysis of pain severity data is complicated by the nonlinear rate of
      resolution. Further, three distinct phases characterize pain resolution--acute,
      subacute, and chronic. Using two clinical trial datasets as the bases for
      analyses, the rates of baseline pain resolution were computed across each of
      three phases and compared for age, severity of pain at onset, and number of
      lesions at baseline. The results defined transition points of 24.4 +/- 3.34 for
      the subacute phase and 110.3 +/- 11.9 days for the chronic phase. The model
      demonstrated a treatment effect of valiciclovir (VACV) during the subacute phase
      as compared to acyclovir (ACV) (P = 0.006) and supports effects of age, baseline
      pain and number lesions on pain cessation rates in the acute phase. This model
      verifies three phases of zoster pain and delineates the impact of treatment and
      other factors on the phase-specific rates of pain cessation.

PMID- 12067776
TI  - Euthanasia in palliative care journals.
AB  - With the growth of palliative care services, interest in moral issues also seems
      to be growing. The controversial issue of euthanasia significantly provokes moral
      reflection on the care for dying patients. This article presents an analysis of
      the moral issue of euthanasia as it is discussed by the palliative care community
      in the professional journals of palliative care. Initially, the analysis will
      focus on describing the characteristics of the publications about euthanasia and
      the attitudes expressed in the articles towards this practice. Second, attention
      will be paid to the description of the uses of the term euthanasia in the various
      articles and also how frequently such uses occur. Third, the various arguments in
      support for or against a place for euthanasia in palliative care will be
      discussed.

PMID- 12067777
TI  - A pilot exploration of the antiemetic activity of olanzapine for the relief of
      nausea in patients with advanced cancer and pain.
AB  - This open-label pilot study explored the antiemetic activity of olanzapine, an
      atypical antipsychotic, in patients with advanced cancer requiring opioid
      analgesics for pain. Fifteen patients received 2 days of a washout and placebo
      "run-in" followed by two day periods on each of three doses of olanzapine (2.5
      mgs, 5 mgs, and 10 mgs). Patients completed a daily food journal as well as the
      Mini Mental State Exam, Simpson Angus Scale, Barnes Akathisia Scale, and the
      Functional Assessment of Cancer Therapy-General across four time periods, with
      special attention being placed on the nausea item. Eleven women and 4 men with
      varied primary cancer sites participated. The average age of the sample was 58
      years (SD = 16.8). All three dose levels were associated with significant
      reductions in nausea compared to baseline. Diary entries recorded by the subjects
      suggested substantial benefits to overall well being and the 5mg condition was
      associated with statistically significant improvement in overall quality of life
      over baseline (F = 12.0, p < 0.005). No extrapyramidal symptoms were noted and
      mental status exams were not changed over the course of the eight days. These
      results suggest an antiemetic effect for olanzapine and indicate the need for a
      controlled trial.

PMID- 12067783
TI  - A culture of mistrust.

PMID- 12067784
TI  - Europe continues breast screening despite doubts.

PMID- 12067785
TI  - Homoharringtonine effective in CML patients.

PMID- 12067787
TI  - Epstein-Barr virus betrays its secrets.

PMID- 12067790
TI  - Danazol linked to ovarian cancer.

PMID- 12067791
TI  - Adjuvant interferon-alpha improves skin cancer survival.

PMID- 12067792
TI  - Tea chemicals confirmed as cancer-busting compounds.

PMID- 12067795
TI  - Light for lightening diagnoses.

PMID- 12067793
TI  - Bone marrow rejection linked to SHIP gene.

PMID- 12067799
TI  - On the relation between induced abortion and breast cancer.

PMID- 12067800
TI  - Breast cancer risk and induced abortion: the debate continues.

PMID- 12067802
TI  - Mammography screening.

PMID- 12067803
TI  - Chernobyl-related ionising radiation exposure and cancer risk: an epidemiological
      review.
AB  - The Chernobyl nuclear accident on 26th April, 1986, led to a massive release of
      radionuclides into the environment. Although vast areas of Europe were affected
      by Chernobyl-related ionising radiation, the accident had the greatest impact in
      Belarus, Ukraine, and the Russian Federation. Epidemiological studies that have
      investigated the link between the Chernobyl accident and cancer have largely
      focused on malignant diseases in children, specifically thyroid cancer and
      leukaemia. There is good evidence to suggest that rates of thyroid cancer in
      children from the countries that were formally part of the Soviet Union have
      risen as a consequence of the Chernobyl accident. The findings for childhood
      leukaemia are less conclusive. Overall rates for this disease do not seem to have
      been affected by the Chernobyl-related ionising radiation, but there may be a
      larger risk of infant leukaemia in contaminated areas of Europe. Among adult
      populations, there is no strong evidence to suggest that risk of thyroid cancer,
      leukaemia, or other malignant disease has increased as a result of the Chernobyl
      accident.

PMID- 12067804
TI  - Concomitant phyllodes tumour and homolateral breast cancer.

PMID- 12067805
TI  - Telomerase inhibition and the future management of head-and-neck cancer.
AB  - Telomeres are tandem repeats of DNA associated with specific proteins. These
      structures cap eukaryotic chromosomes and maintain the integrity of the
      chromosome ends. In the germline, telomeres are maintained by the enzyme
      telomerase, but in normal somatic cells the enzyme's activity is low or
      undetectable. Human tumours, including squamous-cell carcinoma of the head and
      neck (SCCHN), need telomerase to maintain telomere function; inhibition of the
      enzyme can lead to apoptosis. Furthermore, because most tumour cells have very
      short telomeres, they are more likely to succumb to telomerase inhibition than
      normal cells. Telomerase is therefore a potential selective anticancer target.
      The telomere is also involved in the repair of DNA double strand breaks, and
      telomere dysfunction provokes radiosensitivity. In this review we consider
      whether manipulation of telomere function may selectively sensitise SCCHN to
      radiotherapy and discuss the possible pitfalls. We also assess how some
      conventional treatments may affect the subsequent use of telomerase inhibitors.

PMID- 12067806
TI  - A case for geriatric oncology.
AB  - The increase in cancer incidence with increasing age is becoming more obvious and
      more important as the average age of the population increases. The close link
      between old age and cancer development is the result of three main factors: the
      substantial length of time required for carcinogenesis; the occurrence of age
      related molecular changes that mimic carcinogenesis; and, changes in bodily
      environment that favour cancer progression, which is a consequence of increasing
      age. The clinical behaviour of common malignant diseases, eg, breast, ovarian,
      and lung cancers, lymphomas, and acute leukaemias, may change with age because of
      intrinsic variation of the neoplastic cells and the ability of the tumour host to
      support neoplastic growth. Therapeutic decisions should be based on an estimation
      of the patient's life expectancy, and risks and benefits should be weighted up
      accordingly. A comprehensive geriatric assessment of function, comorbidity,
      cognition, depression, social support, nutrition, and polypharmacy, would allow
      interventions to be tailored to individual needs. In developed countries, the
      numbers of older people who develop cancer are increasing and many questions
      remain unanswered. These issues include: the causes of the association of cancer
      and ageing; the age-related differences in cancer biology; the goals of cancer
      treatment in the aged; and the effectiveness of cancer prevention. We review the
      biological and clinical interactions of cancer and ageing and discuss the skills
      and knowledge necessary for caring for older patients.

PMID- 12067807
TI  - Insulin-like growth factors and cancer.
AB  - Interest in insulin-like growth factors (IGFs) and their effect on carcinogenesis
      has increased recently because high serum concentrations of IGF1 are associated
      with an increased risk of breast, prostate, colorectal, and lung cancers.
      Physiologically, IGF1 is the major mediator of the effects of the growth hormone;
      it thus has a strong influence on cell proliferation and differentiation and is a
      potent inhibitor of apoptosis. The action of IGF1 is predominantly mediated
      through the IGF1 receptor (IGF1R). IGF1R is involved in several oncogenic
      transformation processes. The availability of unbound IGF1 for interaction with
      IGF1R is modulated by IGF-binding proteins (IGFBP1-6). IGFBPs, especially IGFBP3,
      have independent effects on cell growth, for example, IGFBP3 has proapoptotic
      activities both dependent on and independent of p53.

PMID- 12067808
TI  - Hormone-replacement therapy and breast cancer.
AB  - Hormone-replacement therapy (HRT) has been available for many years, but the
      important question of its place in development and progression of breast cancer
      remains controversial; provision of reliable risk estimates has been hampered by
      a lack of controlled data. Observational evidence suggests that the risk of
      breast cancer may be increased only if HRT is used long term (ie, for longer than
      10 years) and that the risk falls when use ceases. Systematic bias and the lack
      of adequately powered studies prevent any firm clinical recommendations about the
      prescription of differing HRT regimens and risk, or the effect of HRT on breast
      cancer proliferation and mortality. This review aims to summarise current
      clinical data, justifying the need for prospective controlled trials in healthy
      women as well as those at higher risk of breast cancer or with a personal history
      of the disease.

PMID- 12067809
TI  - Scientists and clinicians test their metal-back to the future with platinum
      compounds.
AB  - After more than two decades of extensive use, drugs based on platinum continue to
      have a major role in cancer treatment. Although systematic approaches to the
      development of new analogues have produced agents with less toxicity and novel
      mechanisms of action, to date such approaches have not achieved more cures than
      can be achieved with the parent compound, cisplatin. Greater gains might be
      expected from accumulating knowledge about what makes cancer cells sensitive or
      resistant to platinum-based chemotherapy. Recent information on drug-efflux
      pathways, including expression of multidrug-resistance protein 2, and on how
      tumour cells behave when their DNA is distorted by a platinum adduct, suggests
      new avenues for translational research. The prospects include modulation of
      cellular handling of platinum compounds and individualised therapy based on
      expression of molecules that determine platinum sensitivity.

PMID- 12067810
TI  - Squamous-cell carcinoma on long-lasting lymphoedema.

PMID- 12067815
TI  - A state of mind.

PMID- 12067816
TI  - DNA microarrays in clinical practice: present or future?

PMID- 12067817
TI  - AIDS and non-AIDS-related malignancies: a new vexing challenge in HIV-positive
      patients. Part II. Cervical and anal squamous epithelial lesions, lung cancer,
      testicular germ cell cancers, and skin cancers.
AB  - As the AIDS epidemic progresses, more and more HIV-infected patients will develop
      malignancies. The natural history of a malignancy may change dramatically in the
      presence of HIV infection. Among the AIDS and non-AIDS malignancies, the most
      frequently reported solid tumors are cervical and anal cancer, testicular germ
      cell tumors, lung cancer, and skin cancer. Regardless of epidemiology and
      outcome, the natural history of the majority of non-AIDS-defining tumors changes
      in the setting of HIV infection. Physicians who treat patients with AIDS and non
      AIDS-related cancers need to become familiar with antiretroviral agents, drug
      drug interactions, and the prophylaxis and management of opportunistic
      infections.

PMID- 12067818
TI  - Endothelial dysfunction in chronic heart failure: clinical and therapeutic
      implications.
AB  - Chronic heart failure is a complex clinical syndrome in which abnormal vascular
      endothelial function has been shown to occur at both the experimental and
      clinical levels. Alterations in endothelial function may contribute to the
      increased vasomotor tone and to the vascular remodeling process observed in
      patients with chronic heart failure. Reduced shear stress, increased activity of
      the various vasoconstricting neurohormonal systems, and increased levels of
      proinflammatory cytokines promote endothelial dysfunction in chronic heart
      failure. This article summarizes the major mechanisms implicated in the
      pathophysiology of abnormal endothelial function in chronic heart failure, as
      well as the novel therapeutic interventions aimed at reducing endothelial
      dysfunction in patients with the syndrome.

PMID- 12067819
TI  - Assessing clinical probability of organic disease in patients with involuntary
      weight loss: a simple score.
AB  - BACKGROUND: Involuntary weight loss (IWL) is a frequent complaint with a
      difficult diagnosis. Any one of a number of different diseases may be the source
      of the symptom. However, there is no universal clinical protocol that can help
      physicians study this complex syndrome. METHODS: In March 1998, we defined a
      diagnostic protocol for the study of IWL. IWL was defined as an involuntary and
      documented weight loss of at least 5% of the usual body weight in the previous 3
      months. We analyzed 78 consecutive patients with IWL who came to our clinic
      between March 1998 and December 2000. RESULTS: An organic disease was found in
      56% of cases; cancer, metabolic and digestive diseases were the most common
      entities. Psychiatric problems were found in 33% of cases. After extensive study,
      an idiopathic group of 11% was identified. The variables that were independently
      predictive of a final diagnosis of organic disease were: age>50 years (OR: 8.6,
      CI 95%: 1.7-43.6), psychiatric symptoms (OR: 0.2, CI 95%: 0.1-0.8), smoking (OR:
      14.3, CI 95% 2.3-74), the presence of guide symptoms (OR: 8.0, CI 95%: 1.8-34.4),
      and anemia (OR: 3.1, CI 95%: 2.5-387). Sixteen percent of the patients died, more
      often those suffering from organic diseases. Based on multivariate regression
      coefficients, a clinical risk score was established. CONCLUSIONS: IWL is a
      complex and frequent syndrome with a 16% rate of mortality during the first year.
      A protocol based on clinical data can help in the management of IWL. Our clinical
      prediction rule may help physicians to identify those patients with IWL who are
      likely to have an underlying organic disease.

PMID- 12067820
TI  - Diagnostic value of C-reactive protein in exudative pleural effusions.
AB  - BACKGROUND: Tests able to help in the diagnostic work-up of pleural exudates are
      needed. C-reactive protein (CRP) may be useful for distinguishing between benign
      and malignant exudates. METHODS: A total of 123 consecutive patients diagnosed as
      having exudative pleural effusion (60 associated with malignancy and 63 benign
      effusions) were included in the study. Sensitivity, specificity, positive and
      negative predictive values (PV+, PV-), and positive and negative likelihood
      ratios (LR+, LR-) were established at different cut-off points. RESULTS: Pleural
      fluid CRP level was 23+/-12 mg/l (mean+/-S.D.) in pleural exudates associated
      with malignancy and 50+/-33 mg/l in benign effusions (P<0.001). With a cut-off
      point below 20 mg/l for malignancy, sensitivity of CRP was 0.50, specificity
      0.89, PV+ 0.81, PV- 0.65, LR+ 4.50, and LR- 0.65. With a cut-off point above 45
      mg/l for benign diseases, sensitivity was 0.44, specificity 0.95, PV+ 0.90, PV-
      0.62, LR+ 8.89, and LR- 0.58. CONCLUSIONS: The pleural CRP level provides useful
      information for the study of pleural exudates. A level below 20 mg/l suggests a
      malignant origin and a level above 45 mg/l virtually rules out this possibility.
      Additional advantages of measuring CRP level are that it is an inexpensive test
      and is easy to perform.

PMID- 12067821
TI  - Evidence of reduced coronary artery disease risk for apolipoprotein epsilon2/3
      heterozygotes.
AB  - BACKGROUND: Polymorphism in the gene for apolipoprotein E (apo E) influences
      lipid metabolism. Relative to the epsilon3 allele, the epsilon4 allele tends to
      increase and the epsilon2 allele tends to decrease total and serum cholesterol,
      but uncertainty remains concerning an influence on the risk of coronary artery
      disease (CAD). It is possible that the influence of apo E alleles on CAD risk is
      influenced by the age of subjects studied. In this study, we examine the
      influence of the epsilon2 and epsilon4 alleles on the risk of CAD in relatively
      young subjects. METHODS: We determined the apo E genotype of 564 Caucasian CAD
      subjects below 50 years of age presenting with symptomatic CAD, either with or
      without prior myocardial infarction, and documented by angiography, and 639
      similarly aged Caucasian control subjects without symptomatic CAD randomly
      selected from the community. RESULTS: The frequency of subjects with the
      epsilon2/3 genotype was significantly lower in CAD subjects than controls (6 vs.
      11%, P<0.01) and, relative to epsilon3/3, the epsilon2/3 genotype was associated
      with a significant reduction in total and LDL-cholesterol in male and female
      control subjects. In contrast, there was no difference in the frequency of
      epsilon4/4 or epsilon4/3 genotypes in CAD cases and controls (30 vs. 26%, NS),
      and the latter genotypes had little influence on total or LDL-cholesterol.
      CONCLUSION: The results indicate a beneficial effect of the epsilon2/3 genotype
      not only on LDL cholesterol but in decreasing the risk of CAD in Caucasians at a
      young age.

PMID- 12067822
TI  - Insulin improves fasting and postprandial lipemia in type 2 diabetes.
AB  - BACKGROUND: The purpose of the investigation presented here was to study the
      effects of insulin therapy in type 2 diabetes mellitus (type 2 DM) not only on
      glycemic control but also on other components of the metabolic syndrome,
      including lipid metabolism, blood pressure, and body weight. METHODS: Twelve
      patients with type 2 DM were studied before and after replacement of
      sulphonylurea treatment with insulin for 4 months. RESULTS: Insulin therapy
      resulted in a significant decrease in fasting glucose levels by 26%; glycated
      hemoglobin decreased by 17% and fructosamine values by 19%. With insulin
      treatment, fasting plasma triglyceride levels decreased by 28% and total HDL
      cholesterol and HDL(3) cholesterol increased by 17 and 11%, respectively. Low
      density lipoprotein (LDL) cholesterol showed no significant change. The magnitude
      of postprandial lipemia after ingestion of a standard fatty meal decreased by
      38%. Insulin treatment was also accompanied by a 21% increase in lipoprotein
      lipase (LPL) activity in postheparin plasma and by a 20% increase in cholesteryl
      ester transfer protein (CETP) activity. Hepatic lipase activity was not changed
      significantly with insulin. Mean BMI decreased from 28.5+/-4.2 to 28.0+/-3.1
      kg/m(2) (P=0.02), which is in keeping with the finding that peripheral insulin
      levels did not increase and which can be explained by the fact that the insulin
      regimen was combined with dietary counseling. Accordingly, blood pressure showed
      no significant change. CONCLUSION: Our study demonstrates that judicious
      replacement of sulfonylurea treatment with insulin therapy, together with dietary
      counseling, can result in a simultaneous improvement in the major stigmata of the
      metabolic syndrome, i.e. a significant improvement in glycemic control and lipid
      metabolism without unfavorable effects on body weight and blood pressure.

PMID- 12067823
TI  - Acute renal failure caused by leptospirosis and Hantavirus infection in an urban
      hospital.
AB  - BACKGROUND: Leptospirosis (LS) and Hantavirus (HV) infection have many common
      clinical manifestations, including acute renal failure. In as much as clinical
      experience with these diseases is quite limited in urban centers, we identified
      cases of Leptospira and HV-induced acute renal failure and compared the clinical
      course and evolution of these diseases. METHODS: Patients hospitalized with acute
      renal failure, suspected to be caused by infection, were retrospectively studied
      over a 13-year period (1985-1998). Based on pertinent clinical data and positive
      serology, a total of 26 patients were included in the study, 17 patients with LS
      and 9 patients with HV infection. RESULTS: Both diseases presented as flu-like
      syndromes with high fever. In LS, 2 patients presented with acute meningitis and
      died soon after admission. Symptoms and signs from other organs began after the
      fifth day of illness. Jaundice occurred in 71% of LS patients but not in HV.
      Hemorrhagic phenomena occurred in both diseases but affected predominantly
      patients with icteric LS. Anuria or oliguria occurred in 76% of patients with LS
      and 78% with HV infection. Laboratory studies demonstrated minor transaminase
      elevations in all patients with LS and in 44% with HV. Hypoprothrombinemia or
      thrombocytopenia was uncommon, although disseminated intravascular coagulation
      (DIC) developed in 2 patients that had icteric Ls and major bleeding. Nephropathy
      was associated with haematuria in 71% with LS and all patients with HV.
      Proteinuria was evident in 35% of patients with LS compared to 78% with HV.
      Abnormal chest radiographs were seen in 24% with LS and in 33% with HV. In both
      diseases, aggressive supportive treatment was given, including hemodialysis or
      peritoneal dialysis in 4/26 patients. Of the 26 patients, 22 survived and four
      died. The latter all had LS, and the causes of death were meningitis and DIC with
      multiple organ failure. Follow-up, after 6 months, showed that renal function had
      returned to normal in the 22 survivors. CONCLUSION: It is important to include LS
      and HV infection in the differential diagnosis of acute renal failure. Both
      diseases present with flu-like symptoms and may be complicated by thrombotic
      microangiopathy with hemorrhagic phenomena and hepatic and pulmonary involvement.
      Jaundice should alert the physician to icteric LS, a severe disease associated
      with significant mortality that requires antimicrobial treatment.

PMID- 12067824
TI  - What effect does Helicobacter pylori infection have on the risk of peptic
      ulceration in patients receiving NSAIDs for rheumatoid arthritis?
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) frequently develop dyspepsia
      which may be due to peptic ulceration. There have been conflicting published data
      on the possible interactive roles of nonsteroidal anti-inflammatory drugs
      (NSAIDs) and colonisation of the gastric antrum with Helicobacter pylori in the
      development of peptic ulceration. METHODS: We have prospectively assessed the
      prevalence of peptic ulcers in dyspeptic RA patients and investigated the factors
      responsible. We endoscoped 100 RA patients comparing the endoscopic findings to
      those in 100 age- and sex-matched dyspeptic control subjects. Data on NSAID
      consumption and Helicobacter colonisation were collected for each patient.
      RESULTS: Endoscopic evidence of peptic ulceration was found in 29 RA patients and
      in 16 of the control subjects (P=0.03). Multiple ulcers (>2) were found in
      significantly more RA patients than in controls (10 vs. 2). NSAIDs were being
      used by 60 RA patients and 22 controls (P<0.001). Helicobacter was found in 41 RA
      patients and in 33 controls (P=NS). The consumption of NSAIDs conferred a
      relative risk (RR) of ulceration of 8.67 (1.19-62.87), while the presence of
      Helicobacter gave a RR for ulcers of 3.71 (0.37-37.35) in RA patients. The RR for
      the combination of NSAID consumption and Helicobacter colonisation was 14.44
      (2.05-101). The corresponding RRs for the dyspeptic controls were 2.13, 1.57 and
      1.42 (all P=NS). CONCLUSIONS: Rheumatoid patients have more major and more
      multiple pathology than age-, sex- and symptom-matched controls. This is due
      mainly to their increased consumption of NSAIDs. The prevalence of Helicobacter
      was no greater in RA patients than in controls, but Helicobacter infection
      increased the risk of NSAID-induced ulceration.

PMID- 12067825
TI  - CT colonoscopy for obstructive sigmoid endometriosis: a new technique for an old
      problem.
AB  - Endometriosis of the sigmoid colon is a pathologic entity which is infrequently
      reported. A 29-year-old woman was admitted to the hospital because of abdominal
      pain, constipation, and menstrual rectal bleeding. Endometriosis was suspected,
      and CT (virtual) colonoscopy showed severe stenosis of the orthosigmoid canal due
      to a submucosal mass. Sigmoidoscopy using a pediatric endoscope was successful,
      and biopsies confirmed the original diagnosis. Non-invasive techniques such as
      endoscopic ultrasound and CT (virtual) colonoscopy now make it possible to
      diagnose sigmoid endometriosis. The latter technique, in particular, is feasible
      and well tolerated.

PMID- 12067826
TI  - Citrate infusion test in the diagnosis of hypocalcemia due to a mutation in the
      calcium-sensing receptor gene.
AB  - The calcium-sensing receptor (Ca-R) is a G-protein-coupled surface receptor that
      plays a crucial role in calcium homeostasis via parathyroid hormone secretion.
      Mutations of this receptor can cause a gain in, or loss of, function, leading to
      hypo- or hypercalcemia, respectively. We report here a family with hypocalcemia
      in whom a heterozygous missense mutation in exon 4 was demonstrated, predicting a
      proline to leucine substitution (P221L) in the extracellular part of the Ca-R.
      Clinical symptoms were limited to fatigue. When serum calcium was further lowered
      via a citrate infusion, a significant increase in circulating iPTH was observed,
      although with lower peak values than in normal controls, suggesting a gain in
      function of the Ca-R. Treatment with calcium supplements and calcitriol led to
      prohibitive hypercalciuria without normalizing serum calcium. The aims of this
      case report are: (1) to present a mutation in the Ca-R with a gain in function at
      a codon where previously loss of function was described, and (2) to suggest that
      measuring circulating iPTH during a citrate infusion in the presence of familial
      hypocalcemia is an additional test to diagnose this particular form of
      hypoparathyroidism.

PMID- 12067827
TI  - Genetic diversity and population structure of Plasmodium falciparum isolates from
      Dakar, Senegal, investigated from microsatellite and antigen determinant loci.
AB  - We investigated the genetic diversity and the population structure of 32
      Plasmodium falciparum blood sample isolates (25 from Dakar city and suburbs and
      seven from other localities in Senegal) with two different types of molecular
      markers, 19 microsatellite and four antigenic determinant loci. Under the same
      technical procedure, microsatellite loci showed a mean number of alleles greater
      than that of antigenic loci. Both markers revealed that 15.6% of blood samples
      were multi-infected. Mean expected heterozygosity calculated from microsatellites
      and antigens was similar, 0.74 and 0.70, respectively. Significant linkage
      disequilibrium was observed from microsatellite loci and antigenic determinant
      loci. This suggests a non-panmictic structure for this sample that could be
      explained by two non-exclusive hypotheses: (i) a particular mating system (i.e.
      clonality), and/or (ii) a population structure in P. falciparum (i.e. Wahlund
      effect). Urban samples could have been drawn from a heterogeneous set of foci
      with different level of parasitic transmission. Moreover, no relationship was
      found between multilocus genotypes and different parameters (i.e. age, sex and
      blood group of parasitized patients; number of trophozoites per microliter of
      blood). The results are discussed taking into account recently published studies
      on malaria population biology.

PMID- 12067828
TI  - The putative haemobartonella that influences Plasmodium falciparum parasitaemia
      in squirrel monkeys is a haemotrophic mycoplasma.
AB  - Splenectomised squirrel monkeys (Saimiri sciureus) are increasingly being used as
      an experimental host for human malaria studies, notably for the assessment of
      candidate vaccines against Plasmodium falciparum blood-stage infection. Recently,
      S. sciureus monkeys in our primate-breeding colony were reported to be
      asymptomatic carriers of a putative Haemobartonella species. Patent
      haemobartonella infection is frequently activated following splenectomy, and may
      interfere with studies on the course of P. falciparum parasitaemia in these
      animals. Here, we show by 16S rRNA gene sequence analysis that this wall-less
      bacterium is not a rickettsia but, instead, is a haemotrophic mycoplasma.
      Haemotrophic mycoplasmas are a newly identified group of mycoplasmas that
      parasitise the surfaces of erythrocytes of a wide variety of vertebrate hosts.

PMID- 12067829
TI  - Dengue hemorrhagic fever epidemiology in Thailand: description and forecasting of
      epidemics.
AB  - Despite the use of a variety of control strategies, dengue hemorrhagic fever
      (DHF) control is a major and permanent challenge for public health services in
      Thailand and in Southeast Asia. In order to improve the efficiency of DHF control
      in Thailand, these activities have to concentrate on areas and populations at
      higher risk, which implies early identification of higher incidence periods. A
      retrospective study of spatial and temporal variations of DHF incidence in all 73
      provinces of Thailand (1983-1995) allowed discrimination between seasonal
      (endemic) transmission dependent on climatic variations and vector density and
      non-seasonal (epidemic) transmission, mainly due to the occurrence of a new virus
      serotype in a population with low immunity. To identify epidemic months, which
      appear significantly clustered, a significant deviation from the monthly average
      incidence was defined. The occurrence of two consecutive epidemic months in a
      given area has a high probability (P = 0.66) of being followed by a cluster of 2
      18 epidemic months (average: 7.7 months). This observation is proposed as a
      warning of epidemic outbreak enabling an early launch of control activities. As
      an example, when this method is retrospectively applied to the studied period,
      11,388 province months (73 provinces x 156 months), 579 epidemic outbreaks (5.1%
      of the total) are identified. Control activities can thus be improved through
      early management and prevention of the 308,636 supplementary cases occurring
      during epidemics (37.0% of the total recorded).

PMID- 12067830
TI  - Herpes simplex virus type 2 US3 blocks apoptosis induced by sorbitol treatment.
AB  - Previously, we established HEp2 cell lines which express the US3 protein kinase
      of herpes simplex virus type 2 upon induction with IPTG. Using these cells, we
      examined whether expression of US3 is sufficient to protect cells from apoptotic
      cell death induced by sorbitol. Cells expressing US3 showed significantly reduced
      nuclear fragmentation in the degree that DNA fragmentation and caspase-3
      activation were suppressed. It is known that stressors such as osmotic shock and
      UV irradiation induce the activation of the JNK (c-Jun N-terminal kinase), which
      can lead to apoptotic cell death. Expression of US3 resulted in the suppression
      of sorbitol-induced phosphorylation of JNK and MKK4/SEK1, suggesting that the
      suppression of apoptotic cell death was due to the attenuation of JNK activity.

PMID- 12067831
TI  - In vivo and in vitro activation of caspase-8 and -3 associated with Helicobacter
      pylori infection.
AB  - In vivo and in vitro studies have shown an increase in apoptosis in gastric
      epithelial cells in persons infected with Helicobacter pylori. H. pylori-induced
      activation of caspase-8 and -3 was evaluated using a human gastric adenocarcinoma
      cell line (AGS) and gastric tissue from humans and monkeys colonized with H.
      pylori. The enzymatic activity of caspase-8 was detected only in AGS cells
      exposed to H. pylori up to 24 h. The active form of caspase-8 was present by
      Western blot after exposure to H. pylori for 3 h and persisted through 24 h.
      Caspase-3 activity was present in AGS cells exposed to H. pylori for 3 h,
      reaching a maximum after 24 h (a sevenfold increase in activity). Caspase-8
      mediated cleavage of procaspase-3 generated a 20-kDa band (indicative of the
      presence of active caspase-3) present only in AGS cells exposed to H. pylori.
      Active caspase-3 staining was markedly increased in gastric mucosa from infected
      persons and animals, compared to uninfected controls by immunohistochemistry.
      Stimulation of downstream events leading to apoptosis, such as the cleavage of
      PARP (poly adenosine-diphosphate-ribose polymerase) and DFF45 (DNA fragmentation
      factor 45) as a result of activation of caspase-3, was evaluated. PARP was
      cleaved, resulting in the presence of both an 89- and a 24-kDa band along with
      DFF45, resulting in the presence of 10- and 12-kDa bands only in gastric cells
      exposed to H. pylori. Our data show that H. pylori stimulates the activation of
      caspases and downstream mediators of caspase-induced apoptosis. This suggests
      that H. pylori-induced apoptosis is mediated through caspase pathways, which
      include the activation of caspase-8 and subsequent cleavage and activation of
      caspase-3. This is consistent with caspase-3 activation that was found in the
      gastric mucosa of humans and monkeys infected with H. pylori.

PMID- 12067832
TI  - Microbial infection and inflammation in the development of chronic lung disease
      of prematurity.
AB  - Bronchopulmonary dysplasia or chronic lung disease of prematurity is a prolonged
      respiratory failure with multifactorial etiology in very low birth-weight
      neonates. This review summarizes current knowledge about the molecular mechanisms
      of different infections and inflammatory responses that are involved in the
      development of chronic lung disease of prematurity.

PMID- 12067833
TI  - Experimental effects of Saccharomyces boulardii on diarrheal pathogens.
AB  - Saccharomyces boulardii is a selected strain of yeast that may have applications
      in the prevention and treatment of intestinal infections. The animal models and
      in vitro studies developed to elucidate the mechanisms of this protection are
      reviewed and discussed.

PMID- 12067834
TI  - The multitalented pore-forming proteins of intracellular pathogens.
AB  - Being an intracellular pathogen demands being able to invade a host cell, to
      circumvent the host immune response and to survive in the intracellular
      environment. Pore-forming proteins are among the innumerable tools used by
      intracellular microorganisms to achieve these goals. Remarkably, this seems to be
      a multipurpose group of proteins that can act in several ways. Making channels
      may signify entering into host cells, inhibiting phagocytosis, escaping
      phagosomes or promoting pathogen dissemination. In certain cases, pore-forming
      proteins are double-edged tools and may benefit the host by eliminating infected
      cells and/or inducing inflammation.

PMID- 12067835
TI  - Human health effects of exposure to Pfiesteria piscicida: a review.
AB  - Since its identification, the dinoflagellate Pfiesteria piscicida has been
      implicated in fish kills and fish disease in the southeastern United States.
      Adverse health effects have been reported in researchers working with the
      organism and in watermen following exposure to a fish kill in Maryland. A
      bioactive secretion is postulated as the cause of these effects but has not yet
      been isolated and chemically characterized. The biology and toxicology of this
      organism remain the topic of debate and research.

PMID- 12067836
TI  - Function and dysfunction of aPKC isoforms for glucose transport in insulin
      sensitive and insulin-resistant states.
AB  - Considerable evidence suggests that atypical protein kinase C isoforms (aPKCs),
      serving downstream of insulin receptor substrates and phosphatidylinositol (PI) 3
      kinase, are required for insulin-stimulated glucose transport in skeletal muscle
      and adipocytes. More recent findings further suggest that aPKCs are activated and
      required for glucose transport responses while serving downstream of 1) proline
      rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase
      D, as during the actions of high concentrations of carbohydrates (glucose,
      sorbitol) and agents that activate 5'-AMP-activated protein kinase (exercise, 5
      amino-imidazole-4-carboxamide-1-beta-D-riboside, dinitrophenol), and 2) Cbl
      dependent PI 3-kinase, as during the action of insulin-sensitizing
      thiazolidinediones. It therefore seems reasonable to postulate that, regardless
      of the initial mechanism, aPKCs may serve as terminal molecular switches for
      activating glucose transport responses. This postulation is of critical
      importance, as it now appears that insulin-stimulated aPKC activation is
      compromised in various states of insulin resistance.

PMID- 12067837
TI  - FFA cause hepatic insulin resistance by inhibiting insulin suppression of
      glycogenolysis.
AB  - Free fatty acids (FFA) have been shown to inhibit insulin suppression of
      endogenous glucose production (EGP). To determine whether this is the result of
      stimulation by FFA of gluconeogenesis (GNG) or glycogenolysis (GL) or a
      combination of both, we have determined rates of GNG and GL (with (2)H(2)O) and
      EGP in 16 healthy nondiabetic volunteers (11 males, 5 females) during euglycemic
      hyperinsulinemic (~450 pM) clamping performed either with or without simultaneous
      intravenous infusion of lipid plus heparin. During insulin infusion, FFA
      decreased from 571 to 30 micromol/l (P < 0.001), EGP from 15.7 to 2.0 micromol x
      kg(-1) x min(-1) (P < 0.01), GNG from 8.2 to 3.7 micromol x kg(-1). min(-1) (P <
      0.05), and GL from 7.4 to -1.7 micromol x kg(-1). min(-1) (P < 0.02). During
      insulin plus lipid/heparin infusion, FFA increased from 499 to 1,247 micromol/l
      (P < 0.001). EGP decreased 64% less than during insulin alone (-5.1 +/- 0.7 vs. 
      13.7 +/- 3.4 micromol x kg(-1). min(-1)). The decrease in GNG was not
      significantly different from the decrease of GNG during insulin alone (-2.6 vs. 
      4.5 micromol x kg(-1). min(-1), not significant). In contrast, GL decreased 66%
      less than during insulin alone (-3.1 vs. -9.2 micromol x kg(-1). min(-1), P <
      0.05). We conclude that insulin suppressed EGP by inhibiting GL more than GNG and
      that elevated plasma FFA levels attenuated the suppression of EGP by interfering
      with insulin suppression of GL.

PMID- 12067838
TI  - Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in
      nondiabetic subjects and IDDM patients.
AB  - Using R-beta-[1-(11)C]hydroxybutyrate and positron emission tomography, we
      studied the effect of acute hyperketonemia (range 0.7-1.7 micromol/ml) on
      cerebral ketone body utilization in six nondiabetic subjects and six insulin
      dependent diabetes mellitus (IDDM) patients with average metabolic control
      (HbA(1c) = 8.1 +/- 1.7%). An infusion of unlabeled R-beta-hydroxybutyrate was
      started 1 h before the bolus injection of R-beta-[1-(11)C]hydroxybutyrate. The
      time course of the radioactivity in the brain was measured during 10 min. For
      both groups, the utilization rate of ketone bodies was found to increase nearly
      proportionally with the plasma concentration of ketone bodies (1.0 +/- 0.3
      micromol/ml for nondiabetic subjects and 1.3 +/- 0.3 micromol/ml for IDDM
      patients). No transport of ketone bodies from the brain could be detected. This
      result, together with a recent study of the tissue concentration of R-beta
      hydroxybutyrate in the brain by magnetic resonance spectroscopy, indicate that,
      also at acute hyperketonemia, the rate-limiting step for ketone body utilization
      is the transport into the brain. No significant difference in transport and
      utilization of ketone bodies could be detected between the nondiabetic subjects
      and the IDDM patients.

PMID- 12067839
TI  - Integrated effects of multiple modulators on human liver glycogen phosphorylase
      a.
AB  - Hepatic glucose production is increased in people with type 2 diabetes. Glucose
      released from storage in liver glycogen by phosphorylase accounts for
      approximately 50% of the glucose produced after an overnight fast. Therefore,
      understanding how glycogenolysis in the liver is regulated is of great
      importance. Toward this goal, we have determined the kinetic characteristics of
      recombinant human liver glycogen phosphorylase a (HLGPa) (active form) and
      compared them with those of the purified rat enzyme (RLGPa). The Michaelis-Menten
      constant (K(m)) of HLGPa for P(i), 5 mM, was about fivefold greater than the K(m)
      of RLGPa. Two P(i) (substrate) concentrations were used (1 and 5 mM) to cover the
      physiological range for P(i). Other effectors were added at estimated
      intracellular concentrations. When added individually, AMP stimulated, whereas
      ADP, ATP and glucose inhibited, activity. These results were similar to those of
      the RLGPa. However, glucose inhibition was about twofold more potent with the
      human enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were
      only minor inhibitors of both enzymes. We reported previously that when all known
      effectors were present in combination at physiological concentrations, the net
      effect was no change in RLGPa activity. However, the same combination reduced
      HLGPa activity, and the inhibition was glucose dependent. We conclude that a
      combination of the known effectors of phosphorylase a activity, when present at
      estimated intracellular concentrations, is inhibitory. Of these effectors, only
      glucose changes greatly in vivo. Thus it may be the major regulator of HLGPa
      activity.

PMID- 12067840
TI  - Effects of caloric restriction on mitochondrial function and gene transcripts in
      rat muscle.
AB  - Rodent skeletal muscle mitochondrial DNA has been shown to be a potential site of
      oxidative damage during aging. Caloric restriction (CR) is reported to reduce
      oxidative stress and prolong life expectancy in rodents. Gene expression
      profiling and measurement of mitochondrial ATP production capacity were performed
      in skeletal muscle of male rats after feeding them either a control diet or
      calorie-restricted diet (60% of control diet) for 36 wk to determine the
      potential mechanism of the beneficial effects of CR. CR enhanced the transcripts
      of genes involved in reactive oxygen free radical scavenging function, tissue
      development, and energy metabolism while decreasing expression of those genes
      involved in signal transduction, stress response, and structural and contractile
      proteins. Real-time PCR measurements confirmed the changes in transcript levels
      of cytochrome-c oxidase III, superoxide dismutase (SOD)1, and SOD2 that were
      noted by the microarray approach. Mitochondrial ATP production and citrate
      synthase were unaltered by the dietary changes. We conclude that CR alters
      transcript levels of several genes in skeletal muscle and that mitochondrial
      function in skeletal muscle remains unaltered by the dietary intervention.
      Alterations in transcripts of many genes involved in reactive oxygen scavenging
      function may contribute to the increase in longevity reported with CR.

PMID- 12067841
TI  - Physiological regulation of the expression of a GLUT4 homolog in fish skeletal
      muscle.
AB  - We have recently cloned a glucose transporter from brown trout muscle (btGLUT)
      with high sequence homology to mammalian GLUT4 that is predominantly expressed in
      red and white skeletal muscle, the two major sites of glucose uptake in trout. To
      study the physiological regulation of this putative fish GLUT4, we have
      investigated the expression of btGLUT in red and white skeletal muscle of trout
      in which blood insulin levels have been altered experimentally. The expression of
      btGLUT in red muscle increased significantly when insulin plasma levels were
      elevated by either insulin or arginine treatment and decreased significantly when
      insulin plasma levels were reduced either by fasting or by feeding a low-protein,
      high-carbohydrate diet. In contrast, the expression of btGLUT in white muscle was
      not affected by changes in the plasma levels of insulin. These results strongly
      suggest that insulin could be regulating the expression of btGLUT in trout red
      muscle in vivo and set the ground to test the hypothesis that btGLUT may be
      considered a GLUT4 homolog in fish.

PMID- 12067842
TI  - Regulation of the human brain natriuretic peptide gene by GATA-4.
AB  - Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in
      the adult heart. We previously showed that the human BNP (hBNP) proximal promoter
      region from -127 to -40 confers myocyte-specific expression. The proximal hBNP
      promoter contains several putative cis elements. Here we tested whether the
      proximal GATA element plays a role in basal and inducible regulation of the hBNP
      promoter. The hBNP promoter was coupled to a luciferase reporter gene
      (1818hBNPLuc) and transferred into neonatal ventricular myocytes (NVM), and
      luciferase activity was measured as an index of hBNP promoter activity. Mutation
      of the putative GATA element at -85 of the hBNP promoter [1818(mGATA)hBNPLuc]
      reduced activity by 97%. To study transactivation of the hBNP promoter, we co
      transfected 1818hBNPLuc with the GATA-4 expression vector. GATA-4 activated
      1818hBNPLuc, and this effect was eliminated by mutation of the proximal GATA
      element. Electrophoretic mobility shift assay showed that an oligonucleotide
      containing the hBNP GATA motif bound to cardiomyocyte nuclear protein, which was
      competed for by a consensus GATA oligonucleotide but not a mutated hBNP GATA
      element. The beta-adrenergic agonist isoproterenol and its second messenger cAMP
      stimulated hBNP promoter activity and binding of nuclear protein to the proximal
      GATA element. Thus the GATA element in the proximal hBNP promoter is involved in
      both basal and inducible transcriptional regulation in cardiac myocytes.

PMID- 12067843
TI  - Effect of gender on lipid kinetics during endurance exercise of moderate
      intensity in untrained subjects.
AB  - We evaluated lipid metabolism during 90 min of moderate-intensity (50% VO(2)
      peak) cycle ergometer exercise in five men and five women who were matched on
      adiposity (24 +/- 2 and 25 +/- 1% body fat, respectively) and aerobic fitness
      (VO(2) peak: 49 +/- 2 and 47 +/- 1 ml x kg fat-free mass(-1) x min(-1),
      respectively). Substrate oxidation and lipid kinetics were measured by using
      indirect calorimetry and [(13)C]palmitate and [(2)H(5)]glycerol tracer infusion.
      The total increase in glycerol and free fatty acid (FFA) rate of appearance
      (R(a)) in plasma during exercise (area under the curve above baseline) was
      approximately 65% greater in women than in men (glycerol R(a): 317 +/- 40 and 195
      +/- 33 micromol/kg, respectively; FFA R(a): 652 +/- 46 and 453 +/- 70
      micromol/kg, respectively; both P < 0.05). Total fatty acid oxidation was similar
      in men and women, but the relative contribution of plasma FFA to total fatty acid
      oxidation was higher in women (76 +/- 5%) than in men (46 +/- 5%; P < 0.05). We
      conclude that lipolysis of adipose tissue triglycerides during moderate-intensity
      exercise is greater in women than in men, who are matched on adiposity and
      fitness. The increase in plasma fatty acid availability leads to a greater rate
      of plasma FFA tissue uptake and oxidation in women than in men. However, total
      fat oxidation is the same in both groups because of a reciprocal decrease in the
      oxidation rate of fatty acids derived from nonplasma sources, presumably
      intramuscular and possibly plasma triglycerides, in women.

PMID- 12067844
TI  - Exercise training increases lipid metabolism gene expression in human skeletal
      muscle.
AB  - The effects of a single bout of exercise and exercise training on the expression
      of genes necessary for the transport and beta-oxidation of fatty acids (FA),
      together with the gene expression of transcription factors implicated in the
      regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4
      female, 28.9 +/- 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m(2),
      range 17-26 kg/m(2)) underwent a 9-day exercise training program of 60 min
      cycling per day at 63% peak oxygen uptake (VO(2 peak); 104 +/- 14 W). On days 1
      and 9 of the program, muscle biopsies were sampled from the vastus lateralis
      muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene
      expression of key components of FA transport [FA translocase (FAT/CD36), plasma
      membrane-associated FA-binding protein], beta-oxidation [carntine
      palmitoyltransferase(CPT) I, beta-hydroxyacyl-CoA dehydrogenase] and
      transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha,
      PPAR gamma, PPAR gamma coactivator 1, sterol regulatory element-binding protein
      1c] were unaltered by exercise when measured at the completion and at 3 h
      postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the
      1-h cycling bout. This increased capacity for lipid oxidation was accompanied by
      an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein
      abundance was also upregulated by exercise training. We conclude that enhanced
      fat oxidation after exercise training is most closely associated with the genes
      involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across
      the mitochondrial membrane (CPT I).

PMID- 12067845
TI  - Insulin fails to alter plasma LCFA metabolism in muscle perfused at similar
      glucose uptake.
AB  - Insulin has been shown to alter long-chain fatty acid (LCFA) metabolism and
      malonyl-CoA production in muscle. However, these alterations may have been
      induced, in part, by the accompanying insulin-induced changes in glucose uptake.
      Thus, to determine the effects of insulin on LCFA metabolism independently of
      changes in glucose uptake, rat hindquarters were perfused with 600 microM
      palmitate and [1-(14)C]palmitate and with either 20 mM glucose and no insulin (G)
      or 6 mM glucose and 250 microU/ml of insulin (I). As dictated by our protocol,
      glucose uptake was not significantly different between the G and I groups (10.3
      +/- 0.6 vs. 11.0 +/- 0.5 micromol x g(-1) x h(-1); P > 0.05). Total palmitate
      uptake and oxidation were not significantly different (P > 0.05) between the G
      (10.1 +/- 1.0 and 0.8 +/- 0.1 nmol x min(-1) x g(-1)) and I (10.2 +/- 0.6 and 1.1
      +/- 0.2 nmol. min(-1) x g(-1)) groups. Preperfusion muscle triglyceride and
      malonyl-CoA levels were not significantly different between the G and I groups
      and did not change significantly during the perfusion (P > 0.05). Similarly,
      muscle triglyceride synthesis was not significantly different between groups (P >
      0.05). These results demonstrate that the presence of insulin under conditions of
      similar glucose uptake does not alter LCFA metabolism and suggest that cellular
      mechanisms induced by carbohydrate availability, but independent of insulin, may
      be important in the regulation of muscle LCFA metabolism.

PMID- 12067846
TI  - Epinephrine effects on insulin-glucose dynamics: the labeled IVGTT two
      compartment minimal model approach.
AB  - The hyperglycemic effects of epinephrine (Epi) are established; however, the
      modulation of Epi-stimulated endogenous glucose production (EGP) by glucose and
      insulin in vivo in humans is less clear. Our aim was to determine the effect of
      exogenously increased plasma Epi concentrations on insulin and glucose dynamics.
      In six normal control subjects, we used the labeled intravenous glucose tolerance
      test (IVGTT) interpreted with the two-compartment minimal model, which provides
      not only glucose effectiveness (S(G)(2*)), insulin sensitivity (S(I)(2*)), and
      plasma clearance rate (PCR) at basal state, but also the time course of EGP.
      Subjects were randomly studied during either saline or Epi infusion (1.5
      microg/min). Exogenous Epi infusion increased plasma Epi concentration to a mean
      value of 2,034 +/- 138 pmol/l. During the stable-label IVGTT, plasma glucose,
      tracer glucose, and insulin concentrations were significantly higher in the Epi
      study. The hormone caused a significant (P < 0.05) reduction in PCR in the Epi
      state when compared with the basal state. The administration of Epi has a
      striking effect on EGP profiles: the nadir of the EGP profiles occurs at 21 +/- 7
      min in the basal state and at 55 +/- 13 min in the Epi state (P < 0.05). In
      conclusion, we have shown by use of a two-compartment minimal model of glucose
      kinetics that elevated plasma Epi concentrations have profound effects at both
      hepatic and tissue levels. In particular, at the liver site, this hormone deeply
      affects, in a time-dependent fashion, the inhibitory effect of insulin on glucose
      release. Our findings may explain how even a normal subject may have the
      propensity to develop glucose intolerance under the influence of small increments
      of Epi during physiological stress.

PMID- 12067847
TI  - Hypothalamic thyrotropin-releasing hormone mRNA responses to hypothyroxinemia
      induced by sleep deprivation.
AB  - Sleep deprivation in rats results in progressive declines in circulating
      concentrations of both total and free thyroxine (T(4)) and triiodothyronine
      (T(3)) without an expected increase in plasma thyroid-stimulating hormone (TSH).
      Administration of thyrotropin-releasing hormone (TRH) results in appropriate
      increases in plasma TSH, free T(4), and free T(3) across experimental days,
      suggesting deficient endogenous TRH production and/or release. This study
      examined transcriptional responses related to TRH regulation following sleep
      deprivation. In situ hybridization was used to detect and quantitate expression
      of mRNAs encoding prepro-TRH and 5'-deiodinase type II (5'-DII) in brain sections
      of six rats sleep deprived for 16-21 days, when there was marked
      hypothyroxinemia, and in sections from animals yoked to the experimental protocol
      as well as from sham controls. TRH transcript levels in the paraventricular
      nucleus (PVN) were essentially unchanged at 15-16 days but increased to about
      threefold control levels in three of four rats sleep deprived for 20-21 days, a
      change comparable to that typically found in prolonged experimental
      hypothyroidism. There was no evidence for suppression of 5'-DII mRNA levels,
      which would be a sign of T(3) feedback downregulation of neurons in the PVN. A
      failure to increase serum TSH in response to hypothyroxinemia and to increased
      prepro-TRH mRNA expression indicates that alterations in posttranscriptional
      stages of TRH synthesis, processing, or release likely mediate the central
      hypothyroidism induced by sleep deprivation.

PMID- 12067848
TI  - Cardiac gene expression profile and lipid accumulation in response to starvation.
AB  - Starvation induces many biochemical and histological changes in the heart;
      however, the molecular events underlying these changes have not been fully
      elucidated. To explore the molecular response of the heart to starvation,
      microarray analysis was performed together with biochemical and histological
      investigations. Serum free fatty acids increased twofold in both 16- and 48-h
      fasted mice, and cardiac triglyceride content increased threefold and sixfold in
      16- and 48-h-fasted mice, respectively. Electron microscopy showed numerous lipid
      droplets in hearts of 48-h-fasted mice, whereas fewer numbers of droplets were
      seen in hearts from 16-h-fasted mice. Expression of 11,000 cardiac genes was
      screened by microarrays. More than 50 and 150 known genes were detected by
      differential expression analysis after 16- and 48-h-fasts, respectively. Genes
      for fatty acid oxidation and gluconeogenesis were increased, and genes for
      glycolysis were decreased. Many other genes for metabolism, signaling/cell cycle,
      cytoskeleton, and tissue antigens were affected by fasting. These data provide a
      broad perspective of the molecular events occurring physiologically in the heart
      in response to starvation.

PMID- 12067849
TI  - Influence of puberty on muscle development at the forearm.
AB  - Despite its fundamental importance for physical development, the growth of the
      muscle system has received relatively little consideration. In this study, we
      analyzed the relationship between cross-sectional area (CSA) of forearm muscles
      and maximal isometric grip force with age and pubertal stage. The study
      population comprised 366 children, adolescents, and young adults from 6 to 23 yr
      of age (185 female) and 107 adults (88 female) aged 29 to 40 yr. By use of
      peripheral quantitative computed tomography, muscle CSA was determined at the
      site of the forearm, whose distance to the ulnar styloid process corresponded to
      65% of forearm length. Both muscle CSA and grip force were higher in prepubertal
      boys than in girls. The gender differences decreased until pubertal stage 3 and
      reincreased thereafter. In girls at pubertal stage 5, muscle CSA no longer
      increased with age (P > 0.4), whereas there was still some age-related increase
      in grip force (P = 0.02). In boys at pubertal stage 5, both muscle CSA and grip
      force continued to increase significantly with age (P < 0.005 each). Specific
      grip force (grip force per muscle CSA) adjusted for forearm length increased by
      almost one-half between 6 and 20 yr of age, with no difference between the
      genders. In conclusion, forearm muscle growth takes a gender-specific course
      during puberty, indicating that it is influenced by hormonal changes. However,
      the increase in specific grip force is similar in both genders and thus appears
      to be independent of sex hormones.

PMID- 12067850
TI  - Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after
      onset of intense aerobic exercise.
AB  - This study investigated whether hyperoxic breathing (100% O(2)) or increasing
      oxidative substrate supply [dichloroacetate (DCA) infusion] would increase
      oxidative phosphorylation and reduce the reliance on substrate phosphorylation at
      the onset of high-intensity aerobic exercise. Eight male subjects cycled at 90%
      maximal O(2) uptake (VO(2 max)) for 90 s in three randomized conditions: 1)
      normoxic breathing and saline infusion over 1 h immediately before exercise
      (CON), 2) normoxic breathing and saline infusion with DCA (100 mg/kg body wt),
      and 3) hyperoxic breathing for 20 min at rest and during exercise and saline
      infusion (HYP). Muscle biopsies from the vastus lateralis were sampled at rest
      and after 30 and 90 s of exercise. DCA infusion increased pyruvate dehydrogenase
      (PDH) activation above CON and HYP (3.10 +/- 0.23, 0.56 +/- 0.08, 0.69 +/- 0.05
      mmol x kg wet muscle(-1) x min(-1), respectively) and significantly increased
      both acetyl-CoA and acetylcarnitine (11.0 +/- 0.7, 2.0 +/- 0.5, 2.2 +/- 0.5
      mmol/kg dry muscle, respectively) at rest. However, DCA and HYP did not alter
      phosphocreatine degradation and lactate accumulation and, therefore, the reliance
      on substrate phosphorylation during 30 s (CON, 51.2 +/- 5.4; DCA, 56.5 +/- 7.1;
      HYP, 69.5 +/- 6.3 mmol ATP/kg dry muscle) and 90 s of exercise (CON, 90.6 +/-
      9.5; DCA, 107.2 +/- 13.0; HYP, 101.2 +/- 15.2 mmol ATP/kg dry muscle). These data
      suggest that the rate of oxidative phosphorylation at the onset of exercise at
      90% VO(2 max) is not limited by oxygen availability to the active muscle or by
      substrate availability (metabolic inertia) at the level of PDH in aerobically
      trained subjects.

PMID- 12067851
TI  - Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid
      and glucose uptake in mice.
AB  - Isotopic techniques were used to test the hypothesis that exercise and nitric
      oxide synthase (NOS) inhibition have distinct effects on tissue-specific fatty
      acid and glucose uptakes in a conscious, chronically catheterized mouse model.
      Uptakes were measured using the radioactive tracers (125)I-labeled beta-methyl-p
      iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-(3)H]glucose (DG) during
      treadmill exercise with and without inhibition of NOS. [(125)I]BMIPP uptake at
      rest differed substantially among tissues with the highest levels in heart. With
      exercise, [(125)I]BMIPP uptake increased in both heart and skeletal muscles. In
      sedentary mice, NOS inhibition induced by nitro-L-arginine methyl ester (L-NAME)
      feeding increased heart and soleus [(125)I]BMIPP uptake. In contrast, exercise,
      but not L-NAME feeding, resulted in increased heart and skeletal muscle [2
      (3)H]DG uptake. Significant interactions were not observed in the effects of
      combined exercise and L-NAME feeding on [(125)I]BMIPP and [2-(3)H]DG uptakes. In
      the conscious mouse, exercise and NOS inhibition produce distinct patterns of
      tissue-specific fatty acid and glucose uptake; NOS is not required for important
      components of exercise-associated metabolic signaling, or other mechanisms
      compensate for the absence of this regulatory mechanism.

PMID- 12067852
TI  - Intrauterine growth restriction in rats is associated with hypertension and renal
      dysfunction in adulthood.
AB  - Epidemiological studies have produced evidence that unfavorable intrauterine
      environments during fetal life may lead to adverse outcomes in adulthood. We have
      previously shown that a low-sodium diet, given to pregnant rats over the last
      week of gestation, results in intrauterine growth restriction (IUGR). We
      hypothesize that pups born with IUGR are more susceptible to the development of
      hypertension in adulthood. IUGR fetuses and rats aged 1 wk were characterized for
      organ growth and renal morphogenesis. The adults (12 wk) were evaluated for
      weight, systolic blood pressure, activity of the renin-angiotensin-aldosterone
      system (RAAS), and renal function; hearts and kidneys underwent a histological
      examination. Brain and cardiac ventricle-to-body ratios were increased in IUGR
      fetuses compared with age-matched controls, whereas the kidney-to-body ratio was
      unchanged. Systolic blood pressure was elevated in both IUGR male and female
      adults. Plasma aldosterone levels were not correlated with increased plasma renin
      activity. Moreover, urinary sodium was decreased, whereas plasma urea was
      elevated in both males and females, and creatinine levels were augmented only in
      females, suggesting a glomerular filtration impairment in IUGR. In our model of
      IUGR induced by a low-sodium diet given to pregnant rats, high blood pressure,
      alteration of the RAAS, and renal dysfunction are observed in adult life.
      Differences observed between male and female adults suggest the importance of
      gender in outcomes in adulthood after IUGR.

PMID- 12067853
TI  - Effect of prolactin on phosphate transport and incorporation in mouse mammary
      gland explants.
AB  - Inorganic phosphate is present in milk at a concentration that is severalfold
      higher than in maternal plasma. In cultured mammary tissues from 12- to 14-day
      pregnant mice, the intracellular concentration of (32)PO(4) was six times higher
      than in the culture medium after a 4-h treatment with (32)PO(4). Of the principal
      lactogenic hormones [insulin (I), cortisol (H), and prolactin (PRL)], only I and
      PRL (in the presence of H and I) stimulated (32)PO(4) uptake into cultured
      mammary tissues; H, by itself or in the presence of I or PRL, inhibited (32)PO(4)
      uptake. All three lactogenic hormones together effected the greatest stimulation
      of (32)PO(4) uptake. Similar hormone effects were observed with regard to
      (32)PO(4) incorporation into lipids and trichloroacetic acid-insoluble molecules.
      In a time course study, the onset of the PRL stimulation of (32)PO(4) uptake and
      incorporation occurred 8-12 h after PRL addition; in dose-response studies, the
      PRL effect was manifested with PRL concentrations of 50 ng/ml and above. From
      kinetic studies, the apparent maximal velocity of PO(4) uptake was determined to
      be approximately 7.7 mM x h(-1) x l cell water(-1); the apparent Michaelis-Menten
      constant was approximately 3-5 mM. The PRL effect on (32)PO(4) uptake was
      abolished when sodium was absent from the uptake medium. These studies thus
      demonstrate a complex interaction of three hormones (I, H, and PRL) in the
      regulation of (32)PO(4) uptake and incorporation into macromolecules in cultured
      mouse mammary tissues.

PMID- 12067854
TI  - Role of cytokines and testosterone in regulating lean body mass and resting
      energy expenditure in HIV-infected men.
AB  - Although catastrophic weight loss is no longer common in HIV-infected men, we
      hypothesized that a more gradual process of cachexia [loss of lean body mass
      (LBM) without severe weight loss, often accompanied by elevated resting energy
      expenditure (REE)] is still common and is driven by excessive production of the
      catabolic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1
      beta (IL-1 beta). We performed a longitudinal analysis of an ongoing cohort study
      of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred
      in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of
      observation, but classical wasting (loss of approximately 10% of weight) was rare
      (2%). Both TNF-alpha (-150 g LBM. ng(-1) x ml(-1), P < 0.02) and IL-1 beta
      production (-130 g LBM x ng(-1) x ml(-1), P < 0.01) by peripheral blood
      mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found
      in 17.7% of the subjects regardless of weight change. IL-1 beta (+9 kcal/day per
      ng/ml, P < 0.002) and TNF-alpha (+10 kcal/day per ng/ml, P < 0.02) production
      predicted Delta REE. Serum free testosterone was inversely associated with TNF
      alpha production and was not an independent predictor of either Delta LBM or
      Delta REE after adjustment for cytokine production. Even though weight loss was
      rare in this cohort of patients treated with highly active antiretroviral
      therapy, loss of LBM was common and was driven by catabolic cytokines and not by
      inadequate dietary intake or hypogonadism.

PMID- 12067855
TI  - Atypical beta-adrenergic effects on insulin signaling and action in beta(3)
      adrenoceptor-deficient brown adipocytes.
AB  - Cross talk between adrenergic and insulin signaling systems may represent a
      fundamental molecular basis of insulin resistance. We have characterized a newly
      established beta(3)-adrenoceptor-deficient (beta(3)-KO) brown adipocyte cell line
      and have used it to selectively investigate the potential role of novel-state and
      typical beta-adrenoceptors (beta-AR) on insulin signaling and action. The novel
      state beta(1)-AR agonist CGP-12177 strongly induced uncoupling protein-1 in
      beta(3)-KO brown adipocytes as opposed to the beta(3)-selective agonist CL
      316,243. Furthermore, CGP-12177 potently reduced insulin-induced glucose uptake
      and glycogen synthesis. Neither the selective beta(1)- and beta(2)-antagonists
      metoprolol and ICI-118,551 nor the nonselective antagonist propranolol blocked
      these effects. The classical beta(1)-AR agonist dobutamine and the beta(2)-AR
      agonist clenbuterol also considerably diminished insulin-induced glucose uptake.
      In contrast to CGP-12177 treatment, these negative effects were completely
      abrogated by metoprolol and ICI-118,551. Stimulation with CGP-12177 did not
      impair insulin receptor kinase activity but decreased insulin receptor substrate
      1 binding to phosphatidylinositol (PI) 3-kinase and activation of protein kinase
      B. Thus the present study characterizes a novel cell system to selectively
      analyze molecular and functional interactions between novel and classical beta
      adrenoceptor types with insulin action. Furthermore, it indicates insulin
      receptor-independent, but PI 3-kinase-dependent, potent negative effects of the
      novel beta(1)-adrenoceptor state on diverse biological end points of insulin
      action.

PMID- 12067856
TI  - Testosterone-induced increase in muscle size in healthy young men is associated
      with muscle fiber hypertrophy.
AB  - Administration of replacement doses of testosterone to healthy hypogonadal men
      and supraphysiological doses to eugonadal men increases muscle size. To determine
      whether testosterone-induced increase in muscle size is due to muscle fiber
      hypertrophy, 61 healthy men, 18-35 yr of age, received monthly injections of a
      long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous
      testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg
      testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by
      magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from
      vastus lateralis muscle in 39 men before and after 20 wk of combined treatment
      with GnRH agonist and testosterone. Administration of GnRH agonist plus TE
      resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and
      2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded
      doses of testosterone administration were associated with testosterone dose and
      concentration-dependent increase in muscle volume measured by MRI (changes in
      vastus lateralis volume, -4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-,
      and 600-mg doses, respectively). Changes in cross-sectional areas of both type I
      and II fibers were dependent on testosterone dose and significantly correlated
      with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers,
      respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations
      during treatment. The men receiving 300 and 600 mg of TE weekly experienced
      significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176
      +/- 186 vs. 4,201 +/- 252 microm(2), P < 0.05 at 300-mg dose, and 3,347 +/- 253
      vs. 4,984 +/- 374 microm(2), P = 0.006 at 600-mg dose) muscle fibers; the men in
      the 600-mg group also had significant increments in cross-sectional area of type
      II (4,060 +/- 401 vs. 5,526 +/- 544 microm(2), P = 0.03) fibers. The relative
      proportions of type I and type II fibers did not change significantly after
      treatment in any group. The myonuclear number per fiber increased significantly
      in men receiving the 300- and 600-mg doses of TE and was significantly correlated
      with testosterone concentration and muscle fiber cross-sectional area. In
      conclusion, the increases in muscle volume in healthy eugonadal men treated with
      graded doses of testosterone are associated with concentration-dependent
      increases in cross-sectional areas of both type I and type II muscle fibers and
      myonuclear number. We conclude that the testosterone induced increase in muscle
      volume is due to muscle fiber hypertrophy.

PMID- 12067857
TI  - Urocortin: a mechanism for the sustained activation of the HPA axis in the late
      gestation ovine fetus?
AB  - We hypothesized that urocortin might be produced in the pituitary of the late
      gestation ovine fetus in a manner that could contribute to the regulation of ACTH
      output. We used in situ hybridization and immunohistochemistry to identify
      urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of
      urocortin mRNA rose during late gestation and were associated temporally with
      rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was
      localized both to cells expressing ACTH and to non-ACTH cells by use of dual
      immunofluorescence histochemistry. Transfection of pituitary cultures with
      urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated
      ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in
      chronically catheterized late-gestation fetal sheep significantly stimulated
      levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in
      the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH.
      Regulation of urocortin by cortisol suggests a mechanism to override negative
      feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal
      function, leading to birth.

PMID- 12067858
TI  - Effects of cortisol on lipolysis and regional interstitial glycerol levels in
      humans.
AB  - Cortisol's effects on lipid metabolism are controversial and may involve
      stimulation of both lipolysis and lipogenesis. This study was undertaken to
      define the role of physiological hypercortisolemia on systemic and regional
      lipolysis in humans. We investigated seven healthy young male volunteers after an
      overnight fast on two occasions by means of microdialysis and palmitate turnover
      in a placebo-controlled manner with a pancreatic pituitary clamp involving
      inhibition with somatostatin and substitution of growth hormone, glucagon, and
      insulin at basal levels. Hydrocortisone infusion increased circulating
      concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial
      glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30
      micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02)
      adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/
      24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were
      comparable. In conclusion, the present study unmistakably shows that cortisol in
      physiological concentrations is a potent stimulus of lipolysis and that this
      effect prevails equally in both femoral and abdominal adipose tissue.

PMID- 12067859
TI  - Effects of endurance training on activity and expression of AMP-activated protein
      kinase isoforms in rat muscles.
AB  - The effects of endurance training on the response of muscle AMP-activated protein
      kinase (AMPK) and acetyl-CoA carboxylase (ACC) to moderate treadmill exercise
      were examined. In red quadriceps, there was a large activation of alpha 2-AMPK
      and inactivation of ACC in response to exercise. This response was greatly
      reduced after training, probably because of reduced metabolic stress. In white
      quadriceps, there were no effects of exercise on AMPK or ACC, but alpha 2
      activity was higher after training because of increased phosphorylation of
      Thr(172). In soleus, there were small increases in alpha 2-activity during
      exercise that were not affected by training. The expression of all seven AMPK
      subunit isoforms was also examined. The beta 2- and gamma 2-isoforms were most
      highly expressed in white quadriceps, and gamma 3 was expressed in red quadriceps
      and soleus. There was a threefold increase in expression of gamma 3 after
      training in red quadriceps only. Our results suggest that gamma 3 might have a
      special role in the adaptation to endurance exercise in muscles utilizing
      oxidative metabolism.

PMID- 12067860
TI  - Leptin increases FA oxidation in lean but not obese human skeletal muscle:
      evidence of peripheral leptin resistance.
AB  - The adipocyte-derived hormone leptin has been shown to acutely increase fatty
      acid (FA) oxidation and decrease esterification in resting rodent skeletal
      muscle. However, the effects of leptin on human skeletal muscle FA metabolism are
      completely unknown. In these studies, we have utilized an isolated human skeletal
      muscle preparation combined with the pulse-chase technique to measure FA
      metabolism with and without leptin in lean and obese human skeletal muscle. Under
      basal conditions (in the absence of leptin), muscle from the obese demonstrated
      significantly elevated levels of total FA uptake (+72%, P = 0.038) and enhanced
      rates of FA esterification into triacylglycerol (+102%, P = 0.042) compared with
      lean subjects. In the presence of leptin, lean muscle had elevated rates of
      endogenous (+103%, P = 0.01) and exogenous (+150%, P = 0.03) palmitate oxidation.
      When the ratio of esterification to exogenous oxidation was examined, leptin
      reduced this ratio (-47%, P = 0.032), demonstrating the increased partitioning of
      FA toward oxidation and away from storage. Contrary to these findings in lean
      muscle, leptin had no effect on FA metabolism in skeletal muscle of the obese.
      This study provides the first evidence that leptin increases FA oxidation in
      skeletal muscle of lean, but not obese humans, thus demonstrating the development
      of leptin resistance in obese human skeletal muscle.

PMID- 12067861
TI  - The hidden cost of anesthesia.

PMID- 12067862
TI  - Solving the problem of spinal-induced hypotension in obstetric anesthesia.

PMID- 12067863
TI  - [Relative anesthesia-cost for laparoscopic cholecystectomy: fairly low].
AB  - PURPOSE: The relative contribution of anesthesia costs to total perioperative
      costs is not known precisely. The goal of this prospective study was to measure
      the proportion of anesthesia costs relative to total hospital costs of elective
      laparoscopic cholecystectomy (LC) for in-patients. METHODS: With Institutional
      approval, the total hospital costs of elective LC for 62 ASA I-III patients were
      analyzed. All direct and indirect variable costs, including salaries of
      anesthesia and surgery teams, were obtained for each patient. Data are expressed
      as mean +/- SEM. RESULTS: Intraoperative anesthesia costs as a percentage of the
      total hospital costs equaled 10.5 +/- 0.3%. Postanesthesia care unit (PACU) cost
      was 3.1 +/- 0.2%. The largest hospital cost category was the operating room with
      37.4 +/- 0.6%. The costs attributed to the ward equaled 31.3 +/- 3%. Other costs
      were generated by radiology (6.2 +/- 1.1%), laboratory (5.4 +/- 0.7%), admission
      unit (3.4 +/- 0.2%), pharmacy (2.0 +/- 0.4%) and administration (0.7 +/- 0.1%).
      CONCLUSION: Even if salaries are included, anesthesia and PACU costs (13.6%)
      represent a small portion only of total hospital costs. Cost savings thus may
      result from improving operating room efficiency and shortening of hospitalisation
      rather than programs aiming at lowering anesthesia costs.

PMID- 12067864
TI  - [Serious intraoperative problems--a five-year review of 83,844 anesthetics].
AB  - PURPOSE: The low incidence of mortality and major morbidity in anesthesia makes
      it difficult to study the pattern of potential accidents and to develop
      preventive strategies. Anesthetic 'near-misses', however, occur more frequently.
      Using data from a simple routine-based system of problem reporting, we have
      analyzed the pattern and causes of serious non-fatal problems, in order to
      improve preventive strategies. METHODS: We prospectively recorded anesthesia
      related information from all anesthetics for five years. The data included
      intraoperative problems, which were graded into four levels, according to
      severity. We analyzed only the serious nonfatal problems, which were sorted
      according to clinical presentation, and also according to which factor was most
      important in the development of the problem. We assessed any untoward
      consequences for the patient, and whether the problems could have been prevented.
      RESULTS: Serious problems were recorded in 315 cases out of 83,844 (0.4%).
      Anesthesia was considered the major contributing factor in 111 cases. Difficult
      intubation, difficult emergence from general anesthesia, allergic reactions,
      arrhythmia and hypotension were the dominating problems. Twenty-six anesthesia
      related problems resulted in changes in level of postoperative care, and one
      patient later died in the intensive care unit after anaphylactic shock. Eighty
      two problems could have been prevented by simple strategies. CONCLUSION: Analysis
      of serious nonfatal problems during anesthesia may contribute to improved
      preventive strategies. Data from a routine-based system are suitable for this
      type of analysis. Intubation, emergence, arrhythmia, hypotension and anaphylaxis
      cause most serious problems, and should be the object of preventive strategies.

PMID- 12067865
TI  - Acupressure and ondansetron for postoperative nausea and vomiting after
      laparoscopic cholecystectomy.
AB  - PURPOSE: To compare the efficacy of acupressure wrist bands and ondansetron for
      the prevention of postoperative nausea and vomiting (PONV). METHODS: One hundred
      and fifty ASA I-II, patients undergoing elective laparoscopic cholecystectomy
      were included in a randomized, prospective, double-blind and placebo-controlled
      study. Patients were divided into three groups of 50. Group I was the control;
      Group II received ondansetron 4 mg iv just prior to induction of anesthesia; in
      Group III acupressure wristbands were applied at the P6 points. Acupressure wrist
      bands were placed inappropriately in Groups I and II. The acupressure wrist bands
      were applied 30 min prior to induction of anesthesia and removed six hours
      following surgery. Anesthesia was standardized. PONV were evaluated separately as
      none, mild, moderate or severe within six hours of patients' arrival in the
      postanesthesia care unit and then at 24 hr after surgery by a blinded observer.
      If patients vomited more than once, they were given 4 mg ondansetron iv as the
      rescue antiemetic. Results were analyzed by Z test. A P value of < 0.05 was taken
      as significant. RESULTS: The incidence of PONV and the requirement of rescue
      medication were significantly lower in both the acupressure and ondansetron
      groups during the first six hours. CONCLUSION: Acupressure at P6 causes a
      significant reduction in the incidence of PONV and the requirement for rescue
      medication in the first six hours following laparoscopic cholecystectomy, similar
      to that of ondansetron 4 mg iv.

PMID- 12067866
TI  - Loss of intrathecal morphine analgesia in terminal cancer patients is associated
      with high levels of excitatory amino acids in the CSF.
AB  - PURPOSE: To examine excitatory amino acid (EAA) levels in the cerebrospinal fluid
      (CSF) of patients on long-term morphine treatment for terminal cancer pain relief
      and to correlate these with morphine's analgesic effect. METHODS: Fourteen
      terminal cancer patients suffering severe pain and requiring long-term opioid
      treatment for pain relief were included. An intrathecal (IT) catheter was
      implanted at the L(3-4)/L(4-5) level and advanced 10 cm in a cephalad direction.
      IT morphine injection was started at 100 microgram q 12 hr with a daily
      incremental dose of 50 microgram until the effective dose was reached. The CSF
      was sampled (2 mL) as follows: 1) before the first IT morphine injection, 2) when
      the effective dose of morphine was reached, 3) when loss of morphine's analgesic
      effect at the effective dose (pain visual analogue scale > 5), and 4) after
      consecutive increases of the morphine dose (50 microgram, IT, daily) for
      satisfactory pain relief and up to double the effective dose. The concentrations
      of glutamate and aspartate in the CSF were determined. RESULTS: CSF levels of
      glutamate and aspartate at the effective dose of morphine were lower than the
      baseline levels and increased when pain intensity increased and when morphine's
      analgesic effect was lost. CONCLUSION: Long-term IT morphine administration was
      accompanied by an increase of EAA level in the CSF that was associated with a
      loss of morphine's analgesic effect.

PMID- 12067867
TI  - Epidural bolus injection with alkalinized lidocaine improves blockade of the
      first sacral segment--a brief report.
AB  - PURPOSE: It has been reported that the addition of epinephrine and/or bicarbonate
      to local anesthetic enhances the depth of epidural blockade and that initial
      partial bolus injection results in greater caudal spread. We evaluated the
      anesthetic effects of lidocaine with epinephrine and/or bicarbonate injected into
      the epidural space by bolus or catheter injection. METHODS: Forty-four patients
      undergoing epidural anesthesia with 17 mL of 2% lidocaine containing 1:200,000
      epinephrine at L4-5 or L5-S1 were randomly divided into four groups. Lidocaine
      was administrated via epidural catheter [lidocaine catheter (LC) group] or Tuohy
      needle (lidocaine bolus group), lidocaine-bicarbonate was administrated via
      catheter (lidocaine-bicarbonate catheter group) or needle [lidocaine-bicarbonate
      bolus (LBB) group]. Pain threshold after repeated electrical stimulation was
      performed at L2 and S1 regions. Motor blockade was evaluated using the Bromage
      scale. Sympathetic blockade was assessed with plethysmographic waveforms from the
      toe. RESULTS: The pain threshold of the S1 dermatome in LBB group was
      significantly higher than in the lidocaine only groups, however, differences in
      the pain threshold at the L2 dermatome among the groups were insignificant. The
      onset of sensory blockade in the S1 dermatome in the LBB group was significantly
      shorter than in the LC group. Significantly greater motor blockade was achieved
      in the lidocaine-bicarbonate groups than in the lidocaine-only groups. The
      amplitude of plethysmographic waveforms significantly increased within each
      group. CONCLUSION: Epidural bolus injection of lidocaine-bicarbonate with
      epinephrine improves the pain threshold and speeds the onset of the blockade of
      the first sacral region.

PMID- 12067868
TI  - Paravertebral somatic nerve blocks for breast surgery in a patient with
      hypertrophic obstructive cardiomyopathy.
AB  - PURPOSE: Patients with hypertrophic obstructive cardiomyopathy (HOCM), a genetic
      disorder resulting in idiopathic myocardial thickening, can present the
      anesthesiologist with significant management difficulties. This report reviews
      the physiology of this important disease process and describes the use of
      paravertebral nerve blocks (PVB) in the management of a patient with HOCM who
      presented for partial mastectomy with axillary lymph node dissection. CLINICAL
      FEATURES: A 72-yr-old female presented for breast cancer surgery with a
      significant past medical history of HOCM diagnosed during hospitalization for non
      small cell lung cancer. PVB were performed at thoracic levels 1-6 and 5 mL of
      0.5% ropivacaine and epinephrine 1:400,000 was injected at each level.
      Intraoperatively the patient required no other medication for analgesia and was
      comfortable and conversant during the two-hour procedure. She remained pain free
      following the operation and did not require any opioid medication until the
      following day. CONCLUSIONS: PVB provide excellent analgesia and are a useful
      alternative anesthetic when faced with the HOCM patient requiring major breast
      surgery.

PMID- 12067869
TI  - Long-term therapy of chronic non-malignant pain with potent opioids in an active
      police officer.
AB  - PURPOSE: To report the successful long-term use of methadone and tramadol in
      treating low back pain in a marine police officer. PRINCIPAL FINDINGS: The
      patient sustained a work-related injury having fallen down stairs while on duty
      in 1990. After multiple operations for a prolapsed L5/S1 intervertebral disk, he
      was first seen at our pain clinic in 1994. Numerous systemic medications,
      invasive procedures, physiotherapy and psychotherapy were used to treat his pain,
      but without sustained effect. Methadone was started in late 1995 and tramadol in
      2000. The current maintenance doses are methadone 20 mg and tramadol 200 mg, both
      twice daily. Apart from some initial disruption, the patient was soon able to
      return to full time work. Regular performance reports from his supervisors have
      always been excellent. CONCLUSION: The use of methadone in this police officer
      with chronic low back pain has been very successful despite the demanding nature
      of his job. The controversy surrounding, and further suggestions regarding long
      term use of opioid therapy for non-malignant pain are discussed.

PMID- 12067870
TI  - A survey of directors of Canadian academic acute pain management services: the
      nursing team members role--a brief report.
AB  - PURPOSE: The purpose of this study was to identify Canadian academic centres with
      Acute Pain Management Service (APMS), and to describe the nature of nursing
      involvement on the APMS. METHODS: Departments of Anesthesiology in the 16
      Canadian medical schools were contacted to obtain a list of affiliated hospitals
      and the person most responsible for acute pain. A questionnaire designed to gain
      insight into nursing involvement on APMS was sent out to the 62 hospitals between
      June 2000 and January 2001. RESULTS: Seventy-six percent of centres responded and
      of these 89% (n = 42) had an APMS. In 76% of APMS nursing was involved on the
      service. Sixty-two percent (n = 26) had a designated nursing team member on the
      APMS who contributed in the realms of patient care, staff and patient education,
      and administrative development. The APMS nurse performed patient rounds
      independently (62%) and with a physician (64%). Decision-making was primarily the
      responsibility of anesthesiology, however, the APMS nurse (38%) and the bedside
      nurse (23%) were involved in some centres. The highest educational attainment in
      the 26 hospitals with an APMS nurse was, diploma RN (27%), BScN (31%) and MSc
      (12%). The distribution of advance practice nursing was nurse practitioner (12%),
      clinical nurse specialist (27%), or both (8%). CONCLUSION: Nursing played an
      important role on the APMS, however, quality acute pain management can only be
      achieved with continuing efforts by anesthesiology, nursing and hospital
      administration to support the role of nurses as essential members of the acute
      pain team.

PMID- 12067871
TI  - Factors associated with refusal to enter a clinical trial: epidural anesthesia is
      a deterrent to participation.
AB  - PURPOSE: To compare patients who participate in a clinical trial for pain
      management involving epidural anesthesia to those who refuse and document their
      reasons for refusing. METHODS: Demographic and health history information was
      collected from 621 female patients who were screened for inclusion in a pain
      management trial involving epidural anesthesia. Patients who completed the
      clinical trial (n = 149) were compared to those who consented to provide
      screening information but did not enter the trial (n = 472). RESULTS: Sixty-seven
      percent of women who refused cited unwillingness to have an epidural as the
      reason for their decision. Non-Caucasians (P < 0.01), patients with no history of
      mood/anxiety disorders (P < 0.016) or systemic disease (P < 0.02), and patients
      with certain types of pain (P < 0.02) were more likely to refuse to participate
      in the clinical trial. A longer duration between recruitment and surgery was also
      found to be associated with higher participation rates (P < 0.01). A logistic
      regression equation significantly predicted which patients would participate or
      refuse (P < 0.0001), indicating that a specific set of health and demographic
      factors strongly influence the decision to participate in a trial. CONCLUSIONS:
      The decision to participate in a clinical trial is viewed as a risk/benefit
      analysis. Factors such as short recruitment to surgery intervals and pre-existing
      pain, which increase the salience of risks associated with the trial, may result
      in lower participation rates. Overall, epidural anesthesia is a strong deterrent
      to participation in a clinical trial.

PMID- 12067872
TI  - Prophylactic ephedrine prevents hypotension during spinal anesthesia for Cesarean
      delivery but does not improve neonatal outcome: a quantitative systematic review.
AB  - PURPOSE: The objective of this systematic review was to assess the effectiveness
      and safety of ephedrine compared with control when given prophylactically to
      prevent hypotension during spinal anesthesia for Cesarean delivery. SOURCE:
      Randomized, controlled trials obtained through MEDLINE, EMBASE, the Cochrane
      Controlled Trials Registry, contact with leading experts, and a reference list of
      published articles were analyzed. The following keywords were utilized: spinal
      anesthesia, hypotension, Cesarean section, pregnancy complications, pregnancy
      outcome, fetal outcome, neonatal outcome, umbilical blood cord gases, vasopressor
      and ephedrine. Clinical trials were considered if they compared prophylactic
      ephedrine, given by any dose or route, vs control. PRINCIPAL FINDINGS: The 14
      clinical trials identified included data from a total of 641 patients. Ephedrine
      was more effective than control for preventing hypotension (relative risk [RR],
      0.73; 95% confidence interval [CI], 0.63 to 0.86). Most importantly, there was no
      difference in the risk of fetal acidosis, defined as umbilical arterial pH < 7.2
      (RR, 1.36; 95% CI, 0.55 to 3.35) or the incidence of low Apgar scores (< 7 or <
      8) at one minute (RR, 0.77; 95% CI, 0.29 to 2.06) and five minutes (RR, 0.72; 95%
      CI, 0.24 to 2.19). CONCLUSIONS: Prophylactic ephedrine is more effective than
      control for preventing hypotension during spinal anesthesia for elective Cesarean
      delivery but a clinically relevant positive effect on neonatal outcome was not
      observed. Therefore, the routine use of prophylactic ephedrine to prevent any
      adverse effects of maternal hypotension following spinal anesthesia for Cesarean
      delivery is not supported by the current systematic review.

PMID- 12067873
TI  - The addition of hydromorphone to epidural fentanyl does not affect analgesia in
      early labour.
AB  - PURPOSE: Epidural fentanyl after a lidocaine and epinephrine test dose, provides
      adequate analgesia and allows for ambulation during early labour. The current
      study was designed to determine the influence of hydromorphone added to an
      epidural fentanyl bolus (e.g., whether there is an increase in duration of
      analgesia). METHODS: Forty-four labouring primigravid women, at less than 5 cm
      cervical dilation, who requested epidural analgesia were enrolled in this
      randomized, double-blind study. After a 3 mL test dose of lidocaine with
      epinephrine, patients received fentanyl 100 microgram (in 10 mL volume). They
      randomly received the fentanyl with either saline or hydromorphone (300
      microgram). After administration of the initial analgesic, pain scores and side
      effects were recorded for each patient at ten, 20, and 30 min, and every 30 min
      thereafter, by an observer blinded to the technique used. RESULTS: The patients
      were taller in the hydromorphone group (P < 0.04). There were no other
      demographic differences between the two groups. The mean duration prior to re
      dose was not significantly different in the group that received hydromorphone
      (135 +/- 52 min) compared to the control group (145 +/- 46 min). Side effects
      were similar between the two groups. No patient in either group experienced any
      detectable motor block. CONCLUSION: In early labouring patients, the addition of
      hydromorphone (300 microgram) to epidural fentanyl (100 microgram after a
      lidocaine and epinephrine test dose) neither prolongs the duration of analgesia
      nor affects the ability to ambulate, and cannot be recommended according to the
      current study.

PMID- 12067874
TI  - A reusable, custom-made warming blanket prevents core hypothermia during major
      neonatal surgery.
AB  - PURPOSE: To introduce a reusable model of neonatal forced air warming blanket for
      intraoperative use during major noncardiac neonatal surgery and to determine
      clinical efficacy of this reusable blanket compared with the commonly used
      disposable blankets. METHODS: Delivered air temperature and calorie uptake of
      standard thermal bodies within the reusable blankets, Bair Hugger(R) blanket
      model 530 and model 555 were studied. Also, an efficacy study was conducted in 90
      neonatal patients scheduled for major noncardiac surgery comparing the reusable
      blanket, the Bair Hugger(R) blanket model 530 and passive heat conservation as a
      control. The covered reusable blanket was used as a rescue procedure if the core
      temperature was < 35.5 degrees C. RESULTS: Delivered air temperature and heat
      transfer from the covered reusable blanket did not differ significantly from
      those of the Bair Hugger(R) blanket model 530 and model 555 (despite 0.75 degrees
      C-1.2 degrees C of heat trapped under the sheet and 1.3 Kcal less energy
      transfer). Temperatures measured underneath patients (correlated to poorly
      perfused areas) were highest using the Bair Hugger(R) blanket model 555. The
      reusable blanket was efficacious in preventing intraoperative core hypothermia
      and not different from the Bair Hugger(R) blanket model 530. About 1/3 of the
      patients in the control group had presented a core temperature < 35.5 degrees C
      but were successfully rescued using the reusable blanket. No adverse events were
      associated with any of these warming methods. CONCLUSION: This study shows the
      clinical efficacy of our reusable blanket for the prevention of core hypothermia
      during major neonatal surgery, which is not different from commonly used
      disposable blankets.

PMID- 12067875
TI  - Awake tracheal intubation through the intubating laryngeal mask airway in a
      patient with halo traction.
AB  - PURPOSE: To report a case of awake tracheal intubation through the intubating
      laryngeal mask airway (ILMA) in a patient with halo traction. CLINICAL FEATURES:
      A 16-yr-old, 40 kg, boy with atlanto-occipital instability and halo traction was
      scheduled for surgery under general anesthesia. The head of the patient was fixed
      in a position of flexion and extension was impossible. Cranial magnetic resonance
      imaging revealed that pharyngeal and laryngeal axes were aligned, but that the
      oral axis was in an extreme divergent plane. The tongue and oropharynx were
      anesthetized with 10% lidocaine spray and bilateral superior laryngeal nerve
      blockade was performed. Under sedation, awake orotracheal intubation via ILMA was
      successful. Fibreoptic bronchoscopy has been recommended for awake tracheal
      intubation in such patients. Other techniques, such as use of the Bullard
      laryngoscope have been described also but awake tracheal intubation through the
      ILMA in patients with a halo device in situ has seldom been reported in the
      medical literature. CONCLUSION: Airway management of patients with cervical spine
      instability includes adequate preoperative evaluation of the airway and choosing
      the appropriate intubation technique. We suggest that the ILMA may be an adequate
      alternative for awake tracheal intubation in patients with an unstable cervical
      spine and cervical immobilization with a halo device.

PMID- 12067877
TI  - Neuroanesthesia and intensive care. Best evidence in anesthetic practice. Harm:
      albumin neither increases nor decreases mortality in critically ill patients.

PMID- 12067876
TI  - Cricoid pressure decreases ease of tracheal intubation using fibreoptic
      laryngoscopy (WuScope System.
AB  - PURPOSE: Cricoid pressure is commonly used during rapid sequence induction and
      intubation to minimize the risk of aspiration. The objective of the study was to
      evaluate the ease of fibreoptic (WuScope System(TM)) intubation in anesthetized
      adults receiving cricoid pressure. METHODS: The intubation difficulty scale (IDS)
      was used to measure tracheal intubation difficulties in 33 patients undergoing
      elective surgery with general anesthesia and complete neuromuscular blockade.
      Each patient had their trachea intubated under two conditions: with and without
      cricoid pressure. The order of conditions was determined randomly. Cricoid
      pressure was applied by an experienced anesthesia provider. MAIN RESULTS: An IDS
      value of 0 (ideal intubation, that is one performed by the first operator on the
      first attempt, using the first technique with full visualization of the glottis
      and no vocal cord compression) occurred in 30 of 33 patients (91%) without
      cricoid pressure and in 22 of 33 patients (67%) with cricoid pressure (P < 0.05).
      Cricoid pressure compressed the vocal cords in nine patients (27%) and impeded
      tracheal tube placement in five (15%). In three patients (9%), pressure had to be
      released in order to successfully intubate. CONCLUSION: Cricoid pressure may
      impede or even prevent fibreoptic laryngoscopic intubation with the WuScope
      System(TM).

PMID- 12067878
TI  - Continuous jugular venous oximetry in the neurointensive care unit--a brief
      review.
AB  - PURPOSE: To describe the technique of continuous jugular venous oxygen saturation
      (SjVO(2)) monitoring and review its applications in the neurointensive care unit
      (NICU), with special reference to the management of raised intracranial pressure
      (ICP) following severe acute brain injury. SOURCE: This narrative review is based
      on a selection of current literature on SjVO(2) monitoring in conjunction with
      local experience using this technique. PRINCIPAL FINDINGS: Despite limitations,
      the use of SjVO(2) monitoring has the potential to impact on patient care in the
      NICU. The placement of the catheter is relatively simple. Studies have confirmed
      that abnormalities in cerebral venous oxygen saturation are associated with
      adverse outcome following traumatic brain injury. There is evidence that SjVO(2)
      may be a useful adjunct to ICP monitoring of patients with intracranial
      hypertension. Furthermore, managing cerebral extraction of oxygen in conjunction
      with cerebral perfusion pressure may result in an improved outcome. Further
      research in this area is needed. Other indications for SjVO(2) monitoring include
      subarachnoid hemorrhage, cardiopulmonary bypass and following ischemic stroke.
      CONCLUSION: In the past, the management of severe acute brain injury was targeted
      at ICP and perfusion pressure with little consideration for the metabolic
      requirements of the injured brain. SjVO(2) monitoring is another tool the
      intensivist can use to obtain information about the global oxygen requirements of
      the injured brain on a continuous basis. Whether this will impact on care in the
      long term remains to be seen.

PMID- 12067879
TI  - Web-based interactivity using JavaScript.

PMID- 12067880
TI  - Call for re-evaluation of mobile phones in hospitals.

PMID- 12067881
TI  - Sliding of the skin over subcutaneous tissue is another important factor in
      epidural catheter migration.

PMID- 12067882
TI  - Short-acting neuromuscular blocking drugs allow better control of or time.

PMID- 12067883
TI  - The incidence of failed spinal anesthesia, postdural puncture headache and
      backache is similar with Atraucan and Whitacre spinal needles.

PMID- 12067884
TI  - Unexpected laryngoscope failure.

PMID- 12067885
TI  - Does propofol anesthesia increase agitation in neurosurgical patients? - a pilot
      study.

PMID- 12067886
TI  - A continuous perineural infusion of local anesthetic provides effective
      postoperative pain management after lower limb amputation.

PMID- 12067887
TI  - A longer pretreatment interval does not improve cisatracurium precurarization.

PMID- 12067889
TI  - Problems with CO(2) monitoring in a Siemens Kion anesthesia machine.

PMID- 12067888
TI  - Relationship between body mass index and ventilation with the Laryngeal Tube(R)
      in 228 anesthetized paralyzed patients: a pilot study.

PMID- 12067890
TI  - Use of the Laryngeal Tube(R) in a patient with an unstable neck.

PMID- 12067891
TI  - Hormone replacement therapy and the factor V Leiden mutation.

PMID- 12067892
TI  - Uncoupling metabolism and coupling leptin to cardiovascular disease.

PMID- 12067893
TI  - Comparative genetics of atherosclerosis and restenosis: exploration with mouse
      models.

PMID- 12067894
TI  - Regulation of endothelial cell survival and apoptosis during angiogenesis.
AB  - The process of angiogenesis plays an important role in many physiological and
      pathological conditions. Inhibition of endothelial cell (EC) apoptosis providing
      EC survival is thought to be an essential mechanism during angiogenesis. Many of
      the angiogenic growth factors inhibit EC apoptosis. In addition, the adhesion of
      ECs to the extracellular matrix or intercellular adhesion promotes EC survival.
      In contrast, increasing evidence suggests that the induction of EC apoptosis may
      counteract angiogenesis. In this review, we focus on the regulation of EC
      survival and apoptosis during angiogenesis and especially on the effects and
      intracellular signaling promoted by angiogenic growth factors, endogenous
      angiogenic inhibitors (such as angiostatin, endostatin, and thrombospondin-1),
      and the adhesion to the extracellular matrix. Furthermore, we discuss the effects
      of cross talk between adhesion molecules and growth factors. Understanding the
      molecular mechanisms involved in the regulation of EC survival and apoptosis may
      provide new targets for the development of new therapies to enhance angiogenesis
      in the case of tissue-ischemia (eg, the neovascularization of myocardium) or to
      inhibit angiogenesis in the case of neovascularization-dependent disease (eg,
      tumor, diabetic retinopathy).

PMID- 12067895
TI  - Reversal of thrombin-induced deactivation of CD39/ATPDase in endothelial cells by
      HMG-CoA reductase inhibition: effects on Rho-GTPase and adenosine nucleotide
      metabolism.
AB  - Adenosine triphosphate and diphosphate that activate platelet, leukocyte, and
      endothelium functions are hydrolyzed by endothelial CD39/ATPDase. Because
      CD39/ATPDase is downregulated in endothelial cells by inflammation and this may
      be affected by HMG-CoA reductase inhibitors, we examined the role of cerivastatin
      and simvastatin in regulation of endothelial CD39/ATPDase expression, metabolism
      of ATP/ADP, and function in platelets. Thrombin-stimulated endothelial cells in
      vitro were treated with the statins, and hydrolysis of exogenous ADP and ATP was
      assessed by high-performance liquid chromatography and malachite green assay.
      Platelet aggregation studies were performed with endothelial cell supernatants as
      triggers. CD39/ATPDase surface expression by endothelial cells was determined
      immunologically by fluorescence-activated cell sorter, mRNA expression by RT-PCR,
      and thrombin-induced dissociation of Rho-GTPases by Western blotting. Treatment
      by simvastatin or cerivastatin restored impaired metabolism of exogenous ATP and
      ADP in thrombin-activated endothelial cells by preventing thrombin-induced
      downregulation of CD39/ATPDase. In platelet aggregation studies, ATP and ADP
      supernatants of thrombin-activated endothelial cells were less stimulatory in the
      presence of statins than in their absence. Data show that statins preserve
      CD39/ATPDase activity in thrombin-treated endothelial cells involving alterations
      by statins of Rho-GTPase function and CD39/ATPDase expression. Preservation of
      adenine nucleotide metabolism may directly contribute to the observed anti
      thrombotic and anti-inflammatory actions of statins.

PMID- 12067896
TI  - Divergence of angiogenic and vascular permeability signaling by VEGF: inhibition
      of protein kinase C suppresses VEGF-induced angiogenesis, but promotes VEGF
      induced, NO-dependent vascular permeability.
AB  - Vascular endothelial growth factor (VEGF) promotes angiogenesis by a variety of
      mechanisms including stimulation of endothelial cell proliferation and migration
      and increasing vascular permeability. Although its mitogenic activity is mediated
      primarily by the beta(2)-isoforms of protein kinase C (PKC), little is known
      about the signaling pathways transducing its other physiological properties.
      Accordingly, we used a novel inhibitor molecule to examine the role of PKC
      isoforms alpha and beta in mediating VEGF-induced angiogenesis and vascular
      permeability. Because conventional inhibitors of PKC, such as staurosporine or
      calphostin C, also inhibit a variety of other protein kinases, we used a novel
      compound to specifically inhibit PKC. A myristoylated peptide, which mimics the
      pseudosubstrate motif of PKC-alpha and -beta subtypes, has been shown to be a
      highly selective and cell-permeable inhibitor of PKC. Blocking led, as expected,
      to abrogation of VEGF-induced endothelial cell proliferation in vitro. In vivo,
      VEGF-induced angiogenesis was impaired by myristoylated peptide. Surprisingly,
      selective inhibition of PKC induced vascular permeability in vivo via a NO
      dependent mechanism. Moreover, PKC inhibition led to a 6.4-fold induction of NO
      synthase (NOS) activity in endothelial cells. Our findings demonstrate that
      activation of PKC is a major signaling pathway required for VEGF-induced
      proliferation and angiogenesis, whereas vascular permeability was enhanced by
      blocking PKC. Inhibition of calcium-dependent PKC by itself led to induction of
      NOS. Although NOS is a downstream target for VEGF-induced angiogenesis, its
      induction by PKC inhibition was not sufficient to promote neovascularization.
      These results reveal that angiogenesis and vascular permeability induced by VEGF
      are mediated by mechanisms which ultimately diverge.

PMID- 12067897
TI  - Shear stress induces expression of vascular endothelial growth factor receptor
      Flk-1/KDR through the CT-rich Sp1 binding site.
AB  - Fluid shear stress is 1 of the major factors that control gene expression in
      vascular endothelial cells. We investigated the role of shear stress in the
      regulation of the expression of fetal liver kinase-1/kinase domain region (Flk
      1/KDR), a vascular endothelial growth factor receptor, by using human umbilical
      vein endothelial cells. Laminar shear stress (15 dyne/cm2) elevated Flk-1/KDR
      mRNA levels by approximately 3-fold for 8 hours, and the expression was
      upregulated within the range of 5 to 40 dyne/cm2. Deletion analysis of the 5'
      flanking region of the Flk-1/KDR gene promoter by use of a luciferase reporter
      vector revealed that a shear stress-responsive element resided in the sequence
      between -94 and -31 bp, which contained putative nuclear factor-kappaB, activator
      protein-2, and GC-rich Sp1 and CT-rich Sp1 binding sites. Electrophoretic
      mobility shift assay demonstrated that nuclear extract was bound to the GC-rich
      Sp1 sites and the CT-rich Sp1 site with a similar pattern. However, shear stress
      enhanced the DNA-protein interactions only on the CT-rich Sp1 site but not on the
      GC-rich Sp1 sites. A 3-bp mutation in the CT-rich Sp1 site eliminated the
      response to shear stress in electrophoretic mobility shift assay and luciferase
      reporter assay. These results suggest that shear stress induces Flk-1/KDR
      expression through the CT-rich Sp1 binding site.

PMID- 12067898
TI  - Monocyte chemoattractant protein-1 induces proliferation and interleukin-6
      production in human smooth muscle cells by differential activation of nuclear
      factor-kappaB and activator protein-1.
AB  - Inflammatory response and chemotaxis of vascular wall cells play an important
      pathogenic role in the development of atherosclerosis. Monocyte chemoattractant
      protein-1 (MCP-1) is a potent chemoattractant for monocytes. Besides the
      induction of monocyte recruitment, it has been suggested that MCP-1 may directly
      activate smooth muscle cells. We investigated whether MCP-1 affects the
      proliferation and cytokine production of human vascular smooth muscle cells
      (VSMCs) and determined the underlying signal transduction pathways. Stimulation
      of VSMCs with MCP-1 induced proliferation and resulted in a concentration- and
      time-dependent release of the proinflammatory cytokine interleukin-6 (IL-6).
      Pretreatment with pertussis toxin, GF109203X, and pyrrolidine dithiocarbamate
      inhibited MCP-1-dependent IL-6 release, suggesting the involvement of G(i)
      proteins, protein kinase C, and nuclear factor-kappaB (NF-kappaB). MCP-1 also
      induced extracellular signal-regulated kinase, which, along with IL-6 release,
      was inhibited by pertussis toxin. PD98059 prevented MCP-1-induced extracellular
      signal-regulated kinase activation and cell proliferation. MCP-1 stimulated the
      binding activity of NF-kappaB and of activator protein-1 (AP-1). As demonstrated
      by cis element double-stranded (decoy) oligodeoxynucleotides, NF-kappaB was
      involved in IL-6 release by MCP-1, whereas proliferation was dependent on AP-1.
      The results clearly demonstrate that MCP-1 induces differential activation of NF
      kappaB and AP-1 in VSMCs. Thus, our data propose a new mechanism for the
      proatherogenic effect of MCP-1.

PMID- 12067899
TI  - The von Willebrand factor propeptide (VWFpp) traffics an unrelated protein to
      storage.
AB  - The von Willebrand factor (VWF) propeptide (VWFpp) is critical for the targeting
      of VWF multimers to storage granules. VWFpp alone efficiently navigates the
      storage pathway in AtT-20 and endothelial cells and chaperones mature VWF
      multimers to storage granules when the two proteins are expressed in cis or in
      trans. To further define the role of VWFpp in granular sorting, we examined its
      ability to sort an unrelated protein, C3alpha into the regulated secretory
      pathway. Chimeric constructs of VWFpp and the alpha-chain of C3 were developed.
      The C3alpha protein expressed alone did not sort to granules in AtT-20 cells. The
      trans expression of C3alpha and VWFpp resulted in granular storage of VWFpp but
      no corresponding storage of C3alpha. When C3alpha is expressed as a single chain
      molecule with VWFpp that was rendered uncleavable by furin, C3alpha is re-routed
      to storage and is colocalized with VWFpp. The uncleavable protein was expressed
      in bovine aortic endothelial cells where it sorted to Weibel-Palade bodies,
      colocalized with bovine VWF, and was released when agonist stimulated. We now
      demonstrate that VWFpp re-routes a constitutively secreted protein to the
      regulated storage pathway. Furthermore, our studies suggest that the VWFpp
      storage signal is contained within amino acids 201 to 741.

PMID- 12067900
TI  - Central roles of alpha5beta1 integrin and fibronectin in vascular development in
      mouse embryos and embryoid bodies.
AB  - Vascular development and maturation are dependent on the interactions of
      endothelial cell integrins with surrounding extracellular matrix. Previous
      investigations of the primacy of certain integrins in vascular development have
      not addressed whether this could also be a secondary effect due to poor embryonic
      nutrition. Here, we show that the alpha5 integrin subunit and fibronectin have
      critical roles in blood vessel development in mouse embryos and in embryoid
      bodies (EBs) differentiated from embryonic stem cells (a situation in which there
      is no nutritional deficit caused by the mutations). In contrast, vascular
      development in vivo and in vitro is not strongly dependent on alpha(v) or beta3
      integrin subunits. In mouse embryos lacking alpha5 integrin, greatly distended
      blood vessels are seen in the vitelline yolk sac and in the embryo itself.
      Additionally, overall blood vessel pattern complexity is reduced in alpha5-null
      tissues. This defective vascular phenotype is correlated with a decrease in the
      ligand for alpha5 integrin, fibronectin (FN), in the endothelial basement
      membranes. A striking and significant reduction in early capillary plexus
      formation and maturation was apparent in EBs formed from embryonic stem cells
      lacking alpha5 integrin or FN compared with wild-type EBs or EBs lacking alpha(v)
      or beta3 integrin subunits. Vessel phenotype could be partially restored to FN
      null EBs by the addition of whole FN to the culture system. These findings
      confirm a clear role for alpha5 and FN in early blood vessel development not
      dependent on embryo nutrition or alpha(v) or beta3 integrin subunits. Thus,
      successful early vasculogenesis and angiogenesis require alpha5-FN interactions.

PMID- 12067901
TI  - Endogenous vitronectin and plasminogen activator inhibitor-1 promote neointima
      formation in murine carotid arteries.
AB  - We examined the roles of vitronectin and plasminogen activator inhibitor-1 (PAI
      1) in neointima development. Neointima formation after carotid artery ligation or
      chemical injury was significantly greater in wild-type mice than in vitronectin
      deficient (Vn(-/-)) mice. Vascular smooth muscle cell (VSMC) proliferation did
      not differ between groups, suggesting that vitronectin promoted neointima
      development by enhancing VSMC migration. Neointima formation was significantly
      attenuated in PAI-1-deficient (PAI-1(-/-)) mice compared with control mice.
      Because intravascular fibrin may function as a provisional matrix for invading
      VSMCs, we examined potential mechanisms by which vitronectin and PAI-1 regulate
      fibrin stability and fibrin-VSMC interactions. Inhibition of activated protein C
      by PAI-1 was markedly attenuated in vitronectin-deficient plasma. The capacity of
      PAI-1 to inhibit clot lysis was significantly attenuated in vitronectin-deficient
      plasma, and this effect was not explained simply by the PAI-1-stabilizing
      properties of vitronectin. The adhesion and spreading of VSMCs were significantly
      greater on wild-type plasma clots and PAI-1-deficient plasma clots than on
      vitronectin-deficient plasma clots. We conclude that endogenous levels of
      vitronectin and PAI-1 enhance neointima formation in response to vascular
      occlusion or injury. Their effects may be mediated to a significant extent by
      their capacity to promote intravascular fibrin deposition and by the capacity of
      vitronectin to enhance VSMC-fibrin interactions.

PMID- 12067902
TI  - Tranilast prevents activation of transforming growth factor-beta system,
      leukocyte accumulation, and neointimal growth in porcine coronary arteries after
      stenting.
AB  - N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast) prevents the synchronous
      upregulation of isoforms and receptors of the transforming growth factor (TGF)
      beta system after arterial injury and reduces restenosis after human coronary
      angioplasty. However, the effects of tranilast and the importance of the TGF-beta
      system in stent restenosis, in which inward remodeling is unimportant but
      inflammatory cell stimulation of neointima formation is exaggerated, are
      uncertain. Boston minipigs, treated with tranilast or vehicle, were subjected to
      endoluminal stenting, and the expression of TGF-beta1 and TGF-beta3, the
      expression of their signaling receptors ALK-5 and TbetaR-II, leukocyte numbers
      around the stent struts, and neointima development were assessed over 28 days.
      Stenting greatly increased early (5-day) mRNA expression of the 2 TGF-beta
      isoforms and their receptors. Immunohistochemical localization later showed that
      their concentrations were greatest in regions adjacent to stent struts, where
      leukocytes and collagen deposition were prevalent. Tranilast suppressed these
      elevations in TGF-beta mRNAs and reduced their immunoreactive peptides detectable
      around stent struts. The accumulation of leukocytes and deposition of collagen in
      these regions was also greatly inhibited by tranilast. These effects were
      associated with a 48% reduction in maximal neointimal cross-sectional area and
      43% reduction in mean neointimal cross-sectional area at 28 days (P<0.05). We
      conclude that tranilast suppresses neointima development after stenting, effects
      that can be at least partly attributed to its ability to attenuate the induction
      of the TGF-beta system and leukocyte accumulation around stent struts.

PMID- 12067903
TI  - CCAAT/enhancer-binding protein decoy oligodeoxynucleotide inhibition of
      macrophage-rich vascular lesion formation in hypercholesterolemic rabbits.
AB  - Many cytokine genes, including those encoding acute-phase proteins and
      immunoglobulins, share binding sites for the CCAAT/enhancer-binding protein
      (C/EBP) in their 5'-flanking regions, and C/EBP-related transcription factors
      regulate cell proliferation during terminal differentiation. Therefore, C/EBP
      represents an attractive target for inhibiting restenosis after balloon
      angioplasty. In a rabbit model of restenosis that combines balloon injury of the
      carotid artery with cholesterol-mediated chronic inflammation, a decoy
      oligodeoxynucleotide (ODN) capable of neutralizing C/EBP was administered to the
      site of injury for 30 minutes. Electrophoretic mobility shift analysis confirmed
      that C/EBP activity in decoy ODN-treated segments was virtually absent after 2
      days. Morphometric analysis after 28 days revealed significant reduction (up to
      50%) of neointimal formation and intravascular inflammation in decoy ODN-treated
      segments compared with mutant control ODN or vehicle-treated segments. In
      addition, de novo synthesis of endothelin-1 and the number of proliferating cell
      nuclear antigen-positive smooth muscle cells in the vessel wall were markedly
      attenuated at day 3. These findings suggest that decoy ODN-based neutralization
      of C/EBP may be a feasible and effective method to limit restenosis after
      angioplasty brought about, at least in part, by inhibiting the de novo synthesis
      of endothelin-1.

PMID- 12067904
TI  - Distinction in genetic determinants for injury-induced neointimal hyperplasia and
      diet-induced atherosclerosis in inbred mice.
AB  - Five inbred strains of mice differing in susceptibility to diet-induced
      atherosclerosis were compared for neointimal hyperplasia after endothelial
      denudation with an epoxy resin-modified catheter probe. Results showed that all
      animals responded similarly to the arterial injury, with increased medial area
      and thickness after 14 days. In contrast, a significant strain-specific
      difference in neointimal formation after injury was observed. The atherosclerosis
      susceptible C57L/J mice were also susceptible to injury-induced neointimal
      hyperplasia, and the C3H mice were resistant to both forms of vascular diseases.
      The 129/Sv mice, which displayed an intermediate level of diet-induced
      atherosclerosis, also displayed an intermediate level of injury-induced
      neointimal hyperplasia. Interestingly, the atherosclerosis-susceptible C57BL/6
      mice were resistant to neointimal hyperplasia after endothelial denudation,
      whereas the atherosclerosis-resistant FVB/N mice were susceptible, displaying
      massive neointimal hyperplasia after arterial injury. All (C57L/JxC57BL/6)F1
      hybrid mice were resistant to injury-induced neointimal hyperplasia. Moreover, N2
      mice generated from backcrossing the F1 hybrid mice to the susceptible C57L/J
      mice displayed a range of arterial response to injury, spanning the most severe
      to the most resistant phenotype. These results indicate that injury-induced
      neointimal hyperplasia and diet-induced atherosclerosis are controlled by
      distinct sets of genes; the former appeared to be determined by recessive genes
      at > or =2 loci.

PMID- 12067905
TI  - Respiratory uncoupling lowers blood pressure through a leptin-dependent mechanism
      in genetically obese mice.
AB  - Insulin resistance is commonly associated with hypertension, a condition that
      causes vascular disease in people with obesity and type 2 diabetes. The
      mechanisms linking hypertension and insulin resistance are poorly understood. To
      determine whether respiratory uncoupling can prevent insulin resistance-related
      hypertension, we crossed transgenic mice expressing uncoupling protein 1 (UCP1)
      in skeletal muscle with lethal yellow (A(y)/a) mice, genetically obese animals
      known to have elevated blood pressure. Despite increased food intake, UCP-A(y)/a
      mice weighed less than their A(y)/a littermates. The metabolic rate was higher in
      UCP-A(y)/a mice than in A(y)/a mice and did not impair their ability to alter
      oxygen consumption in response to temperature changes, an adaptation involving
      sympathetic nervous system activity. Compared with their nontransgenic
      littermates, UCP-A(y)/a mice had lower fasting insulin, glucose, triglyceride,
      and cholesterol levels and were more insulin sensitive. Blood pressure, serum
      leptin, and urinary catecholamine levels were also lower in uncoupled mice.
      Independent of sympathetic nervous system activity, low-dose peripheral leptin
      infusion increased blood pressure in UCP-A(y)/a mice but not in their A(y)/a
      littermates. These data indicate that skeletal muscle respiratory uncoupling
      reverses insulin resistance and lowers blood pressure in genetic obesity without
      affecting thermoregulation. The data also suggest that uncoupling could decrease
      the risk of atherosclerosis in type 2 diabetes.

PMID- 12067906
TI  - Propagermanium reduces atherosclerosis in apolipoprotein E knockout mice via
      inhibition of macrophage infiltration.
AB  - Monocyte chemoattractant protein-1 (MCP-1), which binds to C-C chemokine receptor
      2, has been implicated as the primary source of monocyte chemoattractant function
      in the early stages of atherosclerosis. Recently, propagermanium, a drug used
      clinically for the treatment of chronic hepatitis in Japan, has been shown to
      inhibit C-C chemokine receptor 2 function and suppress monocyte/macrophage
      infiltration in vitro and in vivo. Given the importance of monocyte infiltration
      in atherogenesis, the inhibition of it by propagermanium might prevent
      atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were fed an atherogenic
      high cholesterol diet with or without 0.005% propagermanium for 8 or 12 weeks.
      Although the plasma lipid levels were unchanged by the drug treatment,
      atherosclerotic lesion area in the aortic root was reduced by 50% in the drug
      treated apoE-KO mice compared with the nontreated apoE-KO mice after 8 weeks of
      cholesterol feeding (0.62+/-0.12 versus 1.27+/-0.07 mm2, respectively; P<0.01).
      Moreover, the accumulation of macrophages in the lesions was markedly reduced in
      the drug-treated group (macrophage positive area, 0.23+/-0.06 mm2 [drug-treated
      group] versus 0.67+/-0.07 mm2 [control group]; P<0.01). After 12 weeks of
      cholesterol feeding, atherosclerotic lesion formation in the aortic root and in
      the descending thoracic aorta was significantly reduced in the drug-treated
      group. Inhibition of macrophage infiltration by propagermanium prevented the
      formation of atherosclerotic lesions in apoE-KO mice. This drug may serve as a
      therapeutic tool for the treatment of atherosclerosis.

PMID- 12067907
TI  - Transforming growth factor-beta mediates balance between inflammation and
      fibrosis during plaque progression.
AB  - The transition from stable to rupture-prone and ruptured atherosclerotic plaques
      involves many processes, including an altered balance between inflammation and
      fibrosis. An important mediator of both is transforming growth factor (TGF)-beta,
      and a pivotal role for TGF-beta in atherogenesis has been postulated. Here, we
      determine the in vivo effects of TGF-beta inhibition on plaque progression and
      phenotype in atherosclerosis. Recombinant soluble TGF-beta receptor II
      (TGFbetaRII:Fc), which inhibits TGF-beta signaling, was injected in
      apolipoprotein E-deficient mice for 12 weeks (50 microg, twice a week
      intraperitoneally) as early treatment (treatment age 5 to 17 weeks) and delayed
      treatment (age 17 to 29 weeks). In the early treatment group, inhibition of TGF
      beta signaling treatment resulted in a prominent increase in CD3- and CD45
      positive cells in atherosclerotic lesions. Most profound effects were found in
      the delayed treatment group. Plaque area decreased 37.5% after TGFbetaRII:Fc
      treatment. Moreover, plaque morphology changed into an inflammatory phenotype
      that was low in fibrosis: lipid cores were 64.6% larger, and inflammatory cell
      content had increased 2.7-fold. The amount of fibrosis decreased 49.6%, and
      intraplaque hemorrhages and iron and fibrin deposition were observed frequently.
      TGFbetaRII:Fc treatment did not result in systemic effects. These results reveal
      a pivotal role for TGF-beta in the maintenance of the balance between
      inflammation and fibrosis in atherosclerotic plaques.

PMID- 12067908
TI  - Cyclooxygenase-2-dependent prostacyclin formation is regulated by low density
      lipoprotein cholesterol in vitro.
AB  - Reduction of plasma low density lipoprotein (LDL) levels is associated with a
      reduced risk of myocardial infarction, stroke, and death. Some of this clinical
      benefit may be derived from an improvement in endothelium-dependent vasodilation.
      In the present study, we examined the effects of LDL reduction on cyclooxygenase
      (COX) activity and prostacyclin (PGI2) production. Human umbilical vein
      endothelial cells exposed to reduced concentrations of LDL demonstrated increased
      PGI2 production in a dose-dependent manner (from 0.75+/-0.2 to 2.6+/-0.2 ng/mL,
      P<0.0001). This alteration in PGI2 production did not result from LDL-induced
      changes in PGI2 synthase expression. However, selective inhibition of COX-2, but
      not COX-1, blocked PGI2 production under low cholesterol conditions. Addition of
      exogenous cholesterol induces dose-dependent reductions in endothelial COX-2
      expression as measured by reverse transcription-polymerase chain reaction and by
      Western blotting. Pretreatment of cells with actinomycin D, a transcription
      inhibitor, reduced COX-2-derived PGI2 production by 45.9% (from 0.55+/-0.09 to
      0.25+/-0.08 ng/mL). Taken together, these observations indicate that endothelial
      PGI2 production is regulated by cholesterol at the transcriptional level and that
      cholesterol-sensitive transcriptional pathways that regulate COX-2 expression are
      present in vascular tissue.

PMID- 12067909
TI  - Normal production rate of apolipoprotein B in LDL receptor-deficient mice.
AB  - The low density lipoprotein (LDL) receptor is well known for its role in
      mediating the removal of apolipoprotein B (apoB)-containing lipoproteins from
      plasma. Results from in vitro studies in primary mouse hepatocytes suggest that
      the LDL receptor may also have a role in the regulation of very low density
      lipoprotein (VLDL) production. We conducted in vivo experiments using LDLR-/-,
      LDLR+/-, and wild-type mice (LDLR indicates LDL receptor gene) in which the
      production rate of VLDL was measured after the injection of [35S]methionine and
      the lipase inhibitor Triton WR1339. Despite the fact that LDLR-/- mice had a 3.7
      fold higher total cholesterol level and a 2.1-fold higher triglyceride level than
      those of the wild-type mice, there was no difference in the production rate of
      VLDL triglyceride or VLDL apoB between these groups of animals. Experiments were
      also conducted in apobec1-/- mice, which make only apoB-100, the form of apoB
      that binds to the LDL receptor. Interestingly, the apobec1-/- mice had a
      significantly higher production rate of apoB than did the wild-type mice.
      However, despite significant differences in total cholesterol and triglyceride
      levels, there was no difference in the production rate of total or VLDL
      triglyceride or VLDL apoB between LDLR-/- and LDLR+/- mice on an apobec1-/-
      background. These results indicate that the LDL receptor has no effect on the
      production rate of VLDL triglyceride or apoB in vivo in mice.

PMID- 12067910
TI  - Spontaneous ischemic events in the brain and heart adapt the hearts of severely
      atherosclerotic mice to ischemia.
AB  - To investigate if spontaneous ischemic events in mice with severe multi-organ
      atherosclerosis could adapt to ischemia, apolipoprotein E/LDL receptor knockout
      mice were fed an atherogenic diet for 7 to 9 months. Signs of spontaneous
      ischemia occurred. One to two days later, hearts were excised, Langendorff
      perfused with induced global ischemia, and compared with mice without signs of
      disease. In vivo heart or brain infarctions were verified by heart histology
      and/or increased serum levels of cardiac troponin T and S100B. Hearts of mice
      with spontaneous ischemic events had improved function and reduced Langendorff
      induced infarctions. To investigate the remote preconditioning effect of brain
      ischemia, bilateral ligation of the internal carotid arteries was performed in
      C57BL6 mice. Twenty-four hours later, their isolated hearts were protected
      against induced global ischemia. A possible role of inducible NO synthase (iNOS)
      was studied in iNOS knock out mice, who were not preconditioned by induced brain
      ischemia. Cardiac iNOS was unchanged 24 hours after preconditioning, suggesting
      that NO is a trigger rather than a mediator of protection. These findings suggest
      that spontaneous ischemic events in the brain and heart adapt the heart to
      ischemia. This can be mimicked by induced brain ischemia, with iNOS as a key
      factor of protection.

PMID- 12067911
TI  - Fluorescence analysis of biochemical constituents identifies atherosclerotic
      plaque with a thin fibrous cap.
AB  - Vulnerable plaque generally contains a thin fibrous cap, lipid pools, and reduced
      internal plaque collagen. Arterial fluorescence analysis can differentiate
      atherosclerotic lesions from normal arteries; however, the contribution of the
      lipid core to atherosclerotic arterial fluorescence remains controversial. This
      study aimed to identify lipid core fluorophores and to differentiate the lipid
      core from normal artery and atheroma. The helium-cadmium laser-induced
      fluorescence spectra of cadaveric arteries and known chemical constituents were
      recorded. Lipid core fluorescence spectra exhibited marked red shifts and
      broadening compared with the fluorescence spectra of normal tissue and atheroma.
      Similar fluorescence spectra were obtained for lipid core and oxidized low
      density lipoprotein, for atheroma and collagen, and for normal artery and
      elastin. A classification based on collagen, elastin, and oxidized low density
      lipoprotein spectral decomposition could discriminate the lipid core (n=29),
      normal artery (n=74), atheroma (n=73), and preatheroma (n=10) with 86% accuracy.
      Fibrous cap thickness was correlated with the spectral collagen content index
      (r=0.65, P<0.0001), especially at a thickness of <200 microm. We conclude that a
      classification algorithm based on chemical spectral decomposition can accurately
      classify the fluorescence spectra of normal artery, atheroma, and lipid core and
      may be useful in identifying vulnerable atheroma in vivo.

PMID- 12067912
TI  - Genetic influences on aortic root size in American Indians: the Strong Heart
      Study .
AB  - Aortic root dilatation is a major pathophysiological mechanism for aortic
      regurgitation and predisposes the aortic root to dissection or rupture. However,
      only a small proportion of the variance of aortic root size can be explained by
      its known clinical and demographic correlates. The present study was undertaken
      to determine the heritability of echocardiographically derived aortic root
      diameter in the American Indian participants in the second Strong Heart Study
      examination. Echocardiograms were analyzed in 1373 SHS participants who had > or
      =1 family member in the cohort. Heritability calculations were performed by using
      variance component analysis as implemented in SOLAR, a computer analysis program.
      In a polygenic model, the variables entered and identified as covariates of
      larger aortic root diameter were older age, male sex, and center (P<0.001), which
      accounted for 35% of the overall variability of aortic root diameter. After
      simultaneous adjustment was made for these significant covariates, the proportion
      of phenotypic variance due to additive genetic contribution or residual
      heritability (h2) was 0.51 (SE=0.08, P<0.001). Additionally, simultaneous
      adjustment for height, weight, and systolic and diastolic BPs yielded slightly
      lower residual h2 of aortic root diameter (h2=0.44, SE=0.08, P<0.001), which
      accounted for 26% of the overall variance of aortic root size. Because center
      effects were identified as significant covariates in the analyses, h2 analyses
      were performed separately in Arizona, Oklahoma, and North/South Dakota centers,
      which confirmed that a significant proportion of the phenotypic variance of
      aortic root diameter is due to additive genetic contribution. Heredity explains a
      substantial proportion of the variability of aortic root size that is not
      accounted for by age, sex, body size, and blood pressure. Echocardiographic
      screening of family members with aortic root dilatation may identify other
      individuals predisposed to aortic dissection or rupture.

PMID- 12067913
TI  - Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic
      events in women with coronary disease.
AB  - Oral contraceptive use in women with factor V Leiden is associated with increased
      rates of venous thromboembolic events (VTEs). However, the effects of hormone
      replacement therapy (HRT) in postmenopausal women with factor V Leiden are not
      known. A nested case-control study was conducted among women with established
      coronary disease enrolled in 2 randomized clinical trials of HRT, the Heart and
      Estrogen/Progestin Replacement Study (HERS) and the Estrogen Replacement and
      Atherosclerosis (ERA) trial. The Leiden mutation was present in 8 (16.7%) of 48
      cases with VTE compared with only 7 (6.3%) of 112 controls (odds ratio
      [OR](Leiden) 3.3, 95% CI 1.1 to 9.8; P=0.03). In women without the factor V
      Leiden mutation, risk associated with HRT use was significantly increased
      (OR(HRT) 3.7, 95% CI 1.4 to 9.4; P<0.01). On the other hand, in women with the
      factor V Leiden mutation, the estimated risk associated with HRT was increased
      nearly 6-fold, although the CIs were wide and included unity (OR(HRT) 5.7, 95% CI
      0.6 to 53.9; P=0.13). The OR for women with the Leiden mutation who were also
      assigned to HRT compared with wild-type women assigned to placebo was 14.1 (95%
      CI 2.7 to 72.4, P=0.0015). In women with the factor V Leiden mutation who were
      treated with HRT, the estimated absolute incidence of VTE was 15.4 of 1000 per
      year compared with 2.0 of 1000 per year in women without the mutation who were
      taking a placebo (P=0.0015). On the basis of these data, in women with coronary
      disease, the estimated number needed to screen for factor V Leiden to avoid an
      HRT-associated VTE during 5 years of treatment is 376. If factor V Leiden
      genotyping becomes less expensive, it could be cost effective to screen for the
      presence of the mutation before instituting HRT in women with coronary disease.

PMID- 12067914
TI  - Protein C, antithrombin, and venous thromboembolism incidence: a prospective
      population-based study.
AB  - Although deficiencies of protein C and antithrombin, 2 natural plasma
      anticoagulants, are known risk factors for venous thrombosis, population-based
      prospective incidence data on these associations are lacking. Venous
      thromboembolic events have been identified in adults in 2 longitudinal cohort
      studies, the Atherosclerosis Risk in Communities (ARIC) Study and the
      Cardiovascular Health Study (CHS). Incidence was examined in relation to
      prediagnostic plasma levels of protein C (ARIC Study only) and antithrombin. Over
      a mean of 8.1 years of follow-up, there were 130 incident venous thromboembolic
      events that were not due to cancer in the ARIC Study. The age-adjusted incidence
      was elevated 3.36-fold (95% CI 1.24 to 9.11) in the 1.1% of subjects with protein
      C values <2.0 mg/L compared with subjects with higher values. In contrast, in the
      ARIC Study and the CHS, there was no association between low plasma antithrombin
      and venous thromboembolism. In conclusion, in this population-based study, a low
      protein C, but not antithrombin, level has been determined to be associated with
      an increased incidence of venous thromboembolism. Attributable risk estimates
      suggest that low protein C levels account for approximately 2.5% of venous
      thromboembolic events in the ARIC population.

PMID- 12067915
TI  - Ethnicity affects vasodilation, but not endothelial tissue plasminogen activator
      release, in response to bradykinin.
AB  - Previous studies indicate that the vasodilator response to bradykinin (BK) and
      other endothelium-dependent and -independent agonists is decreased in black
      Americans compared with white Americans. The purpose of the present study was to
      determine the effect of ethnicity on fibrinolytic function in humans. Graded
      doses of BK (100, 200, and 400 ng/min), acetylcholine (15, 30, and 60 microg/min;
      N=20), or methacholine (3.2, 6.4, 12.8 microg/min; N=20), and sodium
      nitroprusside (0.8, 1.6, and 3.2 microg/min) were infused via brachial artery in
      19 white and 21 black age-matched normotensive subjects. Forearm blood flow (FBF)
      was measured by plethysmography, and venous and arterial samples were collected
      for tissue plasminogen activator (tPA) antigen. Compared with whites (increase in
      FBF from 3.7+/-0.5 to 23.9+/-2.5 mL x min(-1) x 100 mL(-1)), blacks (increase in
      FBF from 2.8+/-0.3 to 15.2+/-1.9 mL x 100 mL(-1) x min(-1)) exhibited a blunted
      FBF response to BK (P=0.035). Responses to sodium nitroprusside and methacholine
      or acetylcholine were similarly decreased. In contrast, there was no effect of
      ethnicity on net tPA antigen release in response to BK (increase from -0.2+/-0.4
      to 67.3+/-15.2 ng x min(-1) x 100 mL(-1) in blacks; from 0.04+/-0.9 to 65.9+/
      13.6 ng x min(-1) x 100 mL(-1) in whites). Thus, ethnicity significantly
      influenced the relationship between the flow and tPA release responses to BK
      (P=0.037). These data suggest that the BK-dependent alterations in vascular
      fibrinolytic function are preserved in black Americans compared with white
      Americans.

PMID- 12067916
TI  - Rho-GTPase-dependent platelet-neutrophil interaction affected by HMG-CoA
      reductase inhibition with altered adenosine nucleotide release and function.
AB  - Platelet activation and aggregation is considered a crucial step in the
      initiation and aggravation of arterial thrombosis. ADP from activated platelets
      is recognized as major factor in thrombus formation and is a potent stimulator of
      oxygen-free radical release from neutrophils. The aim of the present
      investigation was to determine in vitro the direct effects of statins on ATP and
      ADP secretion by platelets and its impact on subsequent oxidative burst activity
      in neutrophils. Human neutrophils and platelets were isolated from peripheral
      blood. Levels of platelet-derived ATP and ADP were measured by high-performance
      liquid chromatography, oxygen-free radical release of neutrophils was measured
      fluorometrically, and chemotaxis experiments were performed. Rho-GTPases were
      studied by Western blot analysis. Thrombin-activated platelets primed neutrophils
      for enhanced oxygen-free radical release on triggering with formyl-Met-Leu-Phe,
      reduced by cerivastatin and simvastatin treatment of platelets. The two statins
      decreased the amount of adenosine-derivative release in these cells. Rho-GTPases,
      required for the thrombin signaling in platelets and neutrophils, were decreased
      after coincubation with statins. Data demonstrate that inhibition of Rho-GTPases
      by statins inhibit platelet ADP and ATP release and the consecutive augmentation
      of neutrophil oxygen-free radical release. Statins affect platelet-neutrophil
      interactions by altering Rho-GTPase-dependent adenosine nucleotide function.

PMID- 12067917
TI  - Antithrombotic effect of tissue factor inhibition by inactivated factor VIIa: an
      ex vivo human study.
AB  - FFR-rFVIIa is an inactivated recombinant factor VIIa (rFVIIa) that inhibits the
      binding of factor VIIa to tissue factor (TF). It has been shown to prevent TF
      induced thrombosis in animals. The present study is a substudy of the Active Site
      Inhibited Seven (ASIS) trial and examines the antithrombotic effect of 3 doses of
      FFR-rFVIIa in 24 patients undergoing percutaneous coronary intervention (PCI).
      Group 1 (n=9) received 400 microg/kg FFR-rFVIIa and 40 to 50 U/kg heparin, group
      2 (n=7) received 200 microg/kg FFR-rFVIIa and 100 U/kg heparin, and group 3 (n=8)
      received 50 microg/kg FFR-rFVIIa and 100 U/kg heparin. Blood thrombogenicity was
      assessed as total thrombus area and fibrin deposition on the perfusion chamber at
      shear rate conditions typical of mild-moderate coronary stenosis. Baseline blood
      thrombogenicity was evaluated a day before PCI, after heparin administration. A
      second perfusion chamber study was performed just before PCI, 15 minutes after
      the administration of heparin and FFR-rFVIIa. Thrombus formation at a high shear
      rate was markedly reduced in groups 1 and 2 after drug administration, by 79% to
      84% and 76% to 87%, respectively (P<0.004 [group 1], P<0.04 [group 2]). In group
      3, moderate thrombus reduction of 46% to 48% was achieved (P<0.04). Fibrin
      deposition in all 3 groups was nearly eliminated after drug administration. Our
      data demonstrate that FFR-rFVIIa has a potent antithrombotic effect at different
      shear rates and severe arterial injury conditions.

PMID- 12067918
TI  - Elevated fibrinogen and homocysteine levels enhance the risk of mortality in
      patients from a high-risk preventive cardiology clinic.
AB  - Fibrinogen (Fib) plays an important role in platelet aggregation and thrombus
      formation, and homocysteine (tHcy) causes endothelial dysfunction and injury.
      Therefore, an interaction toward an enhanced risk of thrombotic events and
      consequent mortality might be expected in patients with both factors elevated. To
      determine whether patients exposed jointly to high Fib and high tHcy were at
      increased risk of mortality, we compared them with those with only one or neither
      risk factors elevated. Prevalence of coronary artery disease (cross-section) and
      short-term mortality (30+/-14 months) were assessed in 2084 patients with
      available baseline tHcy and Fib. Upper quartiles were used to define high tHcy
      (>14.2 micromol/L) and high Fib (>382 mg/dL). Cox models adjusting for Framingham
      risk score, creatinine, and coronary artery disease status were used to estimate
      the risk of high tHcy and high Fib and their combinations. Mean age of the
      patients was 56+/-12 years (35% women) with 71 (3.4%) recorded deaths. Risk
      adjusted longitudinal models showed a hazard ratio of 2.14 (P=0.03) for isolated
      high tHcy, 2.28 (P=0.02) for isolated high Fib, and 3.29 (P<0.001) for both high
      tHcy and high Fib in comparison with neither risk factor high. Independence of
      each parameter and lack of synergism was found on longitudinal as well as cross
      sectional analyses. Conjoint elevation of Fib and tHcy increased the risk of
      death by approximately 3-fold in three years. Although no significant interaction
      between Fib and tHcy was demonstrated, both provided independent information
      after adjustment for traditional risk factors.

PMID- 12067919
TI  - Adverse event associated with methionine loading test: a case report.
AB  - The death of a control subject after an oral load of methionine for a study of
      the possible relationship between homocysteine and Alzheimer's disease is
      reported. The subject developed postload plasma concentrations of methionine far
      beyond those reported previously in humans given the usual oral loading dose of
      methionine (100 mg/kg body wt). Her preload plasma metabolite values rule out
      known genetic diseases that might predispose one to unusually high methionine
      concentrations. The most likely explanation for these events is that the subject
      received a substantial overdose of methionine. The possibility that extremely
      high methionine concentrations may lead to severe cerebral effects is discussed,
      and it is recommended that any move to increase the sensitivity of the usual
      methionine loading test by increasing the dose of methionine either not be
      undertaken or be taken only with extreme care.

PMID- 12067920
TI  - Validation of homocyst(e)ine-lowering treatment in the era of folic acid
      fortification of cereal grains.

PMID- 12067921
TI  - Hormone replacement therapy, prothrombotic mutations, and the risk of incident
      nonfatal ischemic stroke in postmenopausal women.

PMID- 12067922
TI  - Myocardial infarction: redefined or reinvented?

PMID- 12067923
TI  - Prosthetic valve dysfunction presenting as intermittent acute aortic
      regurgitation.

PMID- 12067925
TI  - Images in cardiology: Existence of muscles surrounding the persistent left
      superior vena cava demonstrated by electroanatomic mapping.

PMID- 12067926
TI  - Images in cardiology: Worm-shaped thrombus mimicking Chiari's network in a
      cocaine user.

PMID- 12067927
TI  - Patients with acute coronary syndrome should start a statin while still in
      hospital.

PMID- 12067929
TI  - Bilateral internal mammary artery grafting: are BIMA better?

PMID- 12067930
TI  - Images in cardiology: Diagnosis of a rare cause of arrhythmogenic syncope by
      means of an implantable loop recorder.

PMID- 12067931
TI  - Images in cardiology: Right atrial lithomyxoma with extramedullary hematopoiesis.

PMID- 12067932
TI  - Antiplatelet treatment in unstable angina: aspirin, clopidogrel, glycoprotein
      IIb/IIIa antagonist, or all three?
AB  - Evidence on the role of antiplatelet agents in patients with non-ST elevation
      acute coronary syndrome is reviewed, and a strategy for their use in unstable
      angina is presented

PMID- 12067933
TI  - Use of statins in the secondary prevention of coronary heart disease: is
      treatment equitable?
AB  - OBJECTIVE: To investigate possible inequities in the use of statins for people
      with coronary heart disease according to a wide range of social and clinical
      factors. DESIGN AND SETTING: Cross sectional analysis of data from the Health
      Survey for England 1998, a population based survey. SUBJECTS: 760 adults with
      coronary heart disease. RESULTS: Only 19.9% of subjects with coronary heart
      disease were receiving lipid lowering drugs (151 of 760; 95% confidence interval
      (CI) 17.0% to 22.7%). The likelihood of receiving statins was greatly reduced for
      older age groups: compared with those aged less than 65 years, the odds of
      receiving statin treatment were 0.53 (95% CI 0.35 to 0.80) for subjects aged 65
      74 years, and 0.11 (95% CI 0.06 to 0.21) for subjects aged 75 years and over.
      Statins were given less often to current cigarette smokers than to non-smokers
      (odds ratio 0.55, 95% CI 0.32 to 0.96), and to subjects with angina compared with
      those with a previous myocardial infarct (odds ratio 0.63, 95% CI 0.43 to 0.93).
      Lower levels of statin use were also seen with increasing time since diagnosis (p
      = 0.12). No clear associations were observed with social measures. CONCLUSIONS:
      Important inequalities were found in the use of statins among people with
      coronary heart disease, which could not be justified by evidence from the large
      statin trials. Proactive policies are required to ensure that the vast majority
      of (if not all) patients with coronary heart disease are receiving statins,
      regardless of age, sex, social class, smoking status, type of coronary heart
      disease, or time since diagnosis.

PMID- 12067934
TI  - Impact of availability and use of coronary interventions on the prescription of
      aspirin and lipid lowering treatment after acute coronary syndromes.
AB  - BACKGROUND: It has been suggested that patients undergoing acute intervention for
      coronary syndromes may not receive adequate secondary prevention. OBJECTIVE: To
      analyse the impact of availability and use of coronary interventions on the
      prescription of secondary prevention after acute coronary syndromes. DESIGN:
      Analysis of a prospective multicentre register of patients admitted to hospital
      for acute coronary syndromes. SETTING: A 1999 pan-European survey in 390
      hospitals. PATIENTS: 3092 patients admitted to hospital with acute coronary
      syndromes (including 777 for ST elevation myocardial infarction within 12 hours
      of onset). MAIN OUTCOME MEASURES: Rates of prescription of aspirin and lipid
      lowering agents. RESULTS: Performance of coronary angiography and percutaneous
      coronary interventions (PCI) during the hospital stay were independent predictors
      of prescription of aspirin at discharge (odds ratio (OR) 1.29 and 1.89, p = 0.053
      and p < 0.0001, respectively). Lipid lowering agents were prescribed more often
      on discharge in patients admitted to hospitals with catheterisation laboratories
      than without (for infarction with ST elevation, 45% v 40% (NS); for other acute
      coronary syndromes, 46% v 36%; p < 0.05). Prescription rates were higher among
      patients undergoing coronary angiography or PCI than in those treated
      conservatively (for infarction with ST elevation, 49%, 53%, and 39%, p < 0.05;
      for other acute coronary syndromes, 50%, 54%, and 34%, p < 0.05). Logistic
      regression analysis showed that PCI was an independent predictor of prescription
      of lipid lowering agents at discharge (OR 1.48, p < 0.0002). CONCLUSIONS:
      Contrary to expectations, invasive procedures for acute coronary syndromes are
      associated with higher rates of prescription of pharmacological secondary
      prevention.

PMID- 12067936
TI  - Low prevalence of lipid lowering drug use in older men with established coronary
      heart disease.
AB  - OBJECTIVE: To determine the prevalence and correlates of lipid lowering drug use
      among older British men with established coronary heart disease (CHD). DESIGN:
      Cross sectional survey within a cohort study (British regional heart study)
      carried out at 20 years of follow up in 1998-2000. SETTING: General practices in
      24 British towns. PARTICIPANTS: 3689 men aged 60-75 years (response rate 76%).
      MAIN OUTCOME MEASURES: Diagnoses of myocardial infarction and angina based on
      detailed review of general practice records. Lipid lowering drug use and blood
      cholesterol concentrations ascertained at 20 year follow up examination. RESULTS:
      Among 286 men with definite myocardial infarction, 102 (36%) were taking a lipid
      lowering drug (93 (33%) a statin); among 360 men with definite angina without
      myocardial infarction, 84 (23%) were taking a lipid lowering drug (78 (21%) a
      statin). Most men with documented CHD who were not receiving a lipid lowering
      drug had a total cholesterol concentration of 5.0 mmol/l or more (87% of those
      with myocardial infarction, 82% with angina). Fewer than half of men with CHD
      receiving a statin had a total cholesterol concentration below 5.0 mmol/l (45% of
      those with myocardial infarction and 47% of those with angina). Only one third of
      the men taking a statin were receiving trial validated dosages. Among men with
      CHD, a history of revascularisation, more recent diagnosis, and younger age at
      diagnosis were associated with a higher probability of receiving lipid lowering
      drug treatment. CONCLUSION: Among patients with established CHD, the prevalence
      of lipid lowering drug use remains low and statin regimens suboptimal. Major
      improvements in secondary prevention are essential if the benefits of statins are
      to be realised.

PMID- 12067937
TI  - Images in cardiology: Intercoronary communication between the circumflex and
      right coronary arteries: distinct from coronary collaterals.

PMID- 12067938
TI  - Seasonality of coronary artery deaths in New South Wales, Australia.
AB  - BACKGROUND: Complex temporal variations in coronary deaths, including diurnal,
      weekly, and seasonal trends, have been reported worldwide. OBJECTIVE: To describe
      the magnitude of seasonal changes in coronary artery deaths in New South Wales,
      Australia. DESIGN: Hospital morbidity data, mortality statistics, and
      meteorological data were modelled using time series techniques to determine
      seasonality of coronary deaths. Data were also analysed to determine whether
      there was an increase in deaths before or after the Christmas and New Year
      holidays. RESULTS: A clear seasonality of coronary deaths was shown, with a peak
      in July. A mean of 2.8 excess coronary deaths per 100 deaths was estimated to
      occur from June to August each year, with a mean annual excess of 224 winter
      deaths a year. Mortality data did not show an increase in coronary death ratios
      before (p = 0.626) or after (p = 0.813) the Christmas and New Year holidays in
      December. CONCLUSIONS: There is a higher incidence of coronary deaths in winter,
      which may reflect winter respiratory infections, the direct effect of cold,
      seasonal changes in lipid concentration, and other factors associated with
      winter. Hospitals should have contingency plans during the winter months to
      manage larger numbers of cardiac admissions.

PMID- 12067939
TI  - Regional left ventricular function during transient coronary occlusion: relation
      with coronary collateral flow.
AB  - OBJECTIVE: To test the hypothesis that regional left ventricular (LV) function
      during balloon angioplasty is related to the amount of collateral flow to the
      ischaemic region. DESIGN: Prospective study. SETTING: Tertiary referral centre.
      METHODS: In 50 patients with coronary artery disease and without myocardial
      infarction, regional systolic and diastolic LV function was determined using
      tissue Doppler ultrasound (TD) before and at the end of a 60 second occlusion of
      a stenotic lesion undergoing percutaneous transluminal coronary angioplasty
      (PTCA) through a pressure guidewire. The study population was subdivided into a
      group with collaterals insufficient (n = 33) and one with collaterals sufficient
      (n = 17) to prevent ECG ST shifts suggestive of myocardial ischaemia during PTCA.
      Pulsed TD was performed from an apical window in the myocardial region supplied
      by the vessel being treated by PTCA. Pressure derived collateral flow index (CFI)
      was determined by simultaneous measurement of mean aortic (P(ao)) and distal
      intracoronary occlusive pressures (P(occl)), where CFI = (P(occl) - 8)/(P(ao) -
      8). RESULTS: At 60 seconds of occlusion, several parameters of systolic and
      diastolic TD derived LV long axis function were significantly different between
      the groups. Also, there was a significant correlation between regional systolic
      excursion velocity, early diastolic excursion velocity, regional isovolumetric
      relaxation time, and CFI. CONCLUSION: During brief coronary artery occlusions,
      regional systolic and diastolic LV function is directly related to the amount of
      collateral flow to this territory.

PMID- 12067940
TI  - Images in cardiology: Unruptured aneurysm of the sinus of Valsalva obstructing
      the right ventricular outflow tract: magnetic resonance imaging findings.

PMID- 12067941
TI  - Prospective analysis of the association of infection with CagA bearing strains of
      Helicobacter pylori and coronary heart disease.
AB  - OBJECTIVE: To see whether it was possible to replicate in a prospective study the
      association recently reported between infection with the more virulent (type 1)
      cytotoxin associated gene A (CagA) antigen carrying strains of Helicobacter
      pylori and increased risk of coronary heart disease. DESIGN AND SETTING: Nested
      case-control study in a clinical outcomes trial. SUBJECTS: Participants in the
      West of Scotland coronary prevention study. METHODS: H pylori CagA serological
      status was determined in plasma samples of 201 subjects (cases) who subsequently
      had a coronary event during follow up and in 414 subjects (controls) matched for
      age and smoking who remained event-free, using a semiquantitative commercial
      enzyme linked immunosorbent assay (ELISA) kit against the p120 antigen of CagA.
      RESULTS: 105 (52%) in the case group and 176 (43%) in the control group were
      seropositive (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.06 to 2.10, p
      = 0.022). The association remained significant after adjustment for blood
      pressure, body mass index, plasma concentrations of low density lipoprotein and
      high density lipoprotein cholesterol, history of hypertension and diabetes,
      statin treatment, and socioeconomic status (OR 1.51, 95% CI 1.06 to 2.16, p =
      0.023). Baseline inflammatory markers (white cell count, C reactive protein,
      fibrinogen) were not significantly increased in either H pylori CagA positive
      cases or controls. CONCLUSIONS: The findings provide support from a prospective
      study for the hypothesis that there is an association between infection with CagA
      bearing strains of H pylori and coronary heart disease. The mechanism(s)
      underlying the association remain to be elucidated.

PMID- 12067943
TI  - Images in cardiology: Thrombus after transcatheter closure of ASD with an
      Amplatzer septal occluder assessed by three dimensional echocardiographic
      reconstruction.

PMID- 12067942
TI  - Incremental changes in QRS duration in serial ECGs over time identify high risk
      elderly patients with heart failure.
AB  - AIMS: To investigate the hypothesis that changes in the ECG over time may be an
      important and readily available marker of prognostic value in patients with heart
      failure. METHODS: 112 elderly patients (81 men) with stable heart failure, a mean
      (SD) age of 73.3 (4.4) years, left ventricular ejection fraction 38 (17)%, and
      peak oxygen consumption 15.1 (4.7) ml/kg/min had ECG measurements on two
      occasions a minimum of 12 (5) months apart. RESULTS: During the subsequent follow
      up period (mean 27 (17) months) 45 patients died. QRS duration (p = 0.001) and
      heart rate (p = 0.03) at baseline were found by Cox proportional hazard method
      analysis to predict adverse outcomes in these patients. Of the changes in ECG
      parameters between the first and second visit, broadening of QRS duration (p =
      0.001) predicted mortality. On Kaplan-Meier survival analysis, patients with < 5%
      change in QRS duration had fewer end points than patients with 5-20% change. A >
      20% increase in QRS duration was associated with the worst prognosis. Progressive
      prolongation of QRS duration correlated closely with deterioration of LV systolic
      and diastolic function. CONCLUSION: A single measurement of QRS duration has
      significant prognostic value in elderly patients with heart failure and the
      increase in QRS duration over time is an even better predictor of adverse out
      comes.

PMID- 12067944
TI  - Images in cardiology: Arrhythmogenic giant submitral left ventricular
      diverticulum.

PMID- 12067945
TI  - Mortality from infective endocarditis: clinical predictors of outcome.
AB  - OBJECTIVE: To identify clinical markers available within the first 48 hours of
      admission that are associated with poor outcome in infective endocarditis.
      DESIGNS: Retrospective cohort study. SETTING: Teaching hospital. PATIENTS: 208 of
      220 patients with infective endocarditis. METHODS: Consecutive patients with
      infective endocarditis presenting between 1981 and 1999 to a tertiary centre were
      studied. Clinical, echocardiographic, and haematological data recorded within 48
      hours of admission were obtained. Data were analysed using logistic regression
      models. MAIN OUTCOMES MEASURES: Mortality at discharge and at six months.
      RESULTS: Data were obtained for 93% of patients who were eligible for inclusion.
      194 (93%) were positive for Duke criteria. Mean age was 52 (1.2) years, and 138
      (66%) were men. 82 (39%) were transferred from other hospitals. 181 (87%) were
      blood culture positive, and 47 (23%) infections were Staphylococcus aureus. The
      infection was located on aortic (n = 85, 41%), mitral (n = 77, 37%), tricuspid (n
      = 18, 9%), and multiple valves (n = 20, 10%). 67 (32%) had prosthetic valve
      endocarditis. 48% of the cohort were managed with antibiotics alone. Mortality at
      discharge was 18% and at six months 27%. Duration of illness before admission,
      age, sex, valve infected, infecting organism, and left ventricular function were
      not predictors of adverse mortality. However, abnormal white cell count, serum
      albumin concentration, serum creatinine concentration, or cardiac rhythm, the
      presence of two major Duke criteria, or visible vegetation conferred a poor
      prognosis. CONCLUSIONS: Conventional prognostic factors in this study did not
      appear to predict outcome early during hospital admission. However, simple
      clinical indices, which are readily available, are reliable, cheap, and
      potentially powerful predictors of poor outcome.

PMID- 12067946
TI  - Images in cardiology: Myocardial infarction and coronary thrombosis.

PMID- 12067948
TI  - Prospective comparison of costs and short term health outcomes of surgical versus
      device closure of atrial septal defect in children.
AB  - OBJECTIVE: To compare surgical and device closure of isolated secundum atrial
      septal defect (ASD) in terms of hospital costs, clinical outcome, and impact on
      the patient and family. DESIGN: Prospective, observational study. SETTING:
      Paediatric tertiary referral centre. PATIENTS: Consecutive local children with a
      secundum ASD, admitted between 1 May 1999 and 1 May 2001. METHODS: Parents
      completed a standardised questionnaire at recruitment (on admission), at
      discharge, and one month after the procedure. Clinical and hospital generated
      cost data were collated at discharge. RESULTS: 62 children were included in the
      analysis: 19 who underwent surgical repair and 43 who underwent device closure
      with the Amplatzer septal occluder. Median procedure times and hospital stay were
      significantly longer for surgical patients (170 (147 to 180) v 92 (70 to 115)
      minutes and 88 (78 to 112) v 29 (28 to 30) hours, respectively; p < 0.01). There
      was no difference in the complication rate. No device patients required intensive
      care or blood products. The median values for postoperative pain score, analgesia
      use, and convalescence time were greater for surgical patients. The median cost
      of each procedure was similar, but higher nursing and laboratory costs
      contributed to a slightly greater total cost for surgical repair (Aus$12 969 ($11
      569 to $14 215) v Aus$11 845 ($10 669 to $12 555), p = 0.03). CONCLUSIONS: Device
      closure of ASD involves a shorter hospital stay, causes less discomfort and
      familial disturbance, and carries less cost than surgical closure. However, there
      should be guarded acceptance of this technique until long term data are
      available.

PMID- 12067947
TI  - Infective endocarditis: determinants of long term outcome.
AB  - OBJECTIVE: To evaluate predictors of long term prognosis in infective
      endocarditis. DESIGN: Retrospective cohort study. SETTING: Tertiary care centre.
      PATIENTS: 212 consecutive patients with infective endocarditis between 1980 and
      1995 MAIN OUTCOME MEASURES: Overall and cardiac mortality; event-free survival;
      and the following events: recurrence, need for late valve surgery, bleeding and
      embolic complications, cerebral dysfunction, congestive heart failure. RESULTS:
      During a mean follow up period of 89 months (range 1-244 months), 56% of patients
      died. In 180 hospital survivors, overall and cardiac mortality amounted to 45%
      and 24%, respectively. By multivariate analysis, early surgical treatment,
      infection by streptococci, age < 55 years, absence of congestive heart failure,
      and > 6 symptoms or signs of endocarditis during active infection were predictive
      of improved overall long term survival. Independent determinants of event-free
      survival were infection by streptococci and age < 55 years. Event-free survival
      was 17% at the end of follow up both in medically-surgically treated patients and
      in medically treated patients. CONCLUSIONS: Long term survival following
      infective endocarditis is 50% after 10 years and is predicted by early surgical
      treatment, age < 55 years, lack of congestive heart failure, and the initial
      presence of more symptoms of endocarditis.

PMID- 12067949
TI  - Images in cardiology: Bilateral origin of a split left anterior descending
      coronary artery combined with atypical branching of the left circumflex coronary
      artery.

PMID- 12067950
TI  - Quality of life in adults with congenital heart disease.
AB  - OBJECTIVE: To examine the quality of life of adults with congenital heart
      disease. DESIGN AND SETTING: Observational, cross sectional study conducted at
      one general hospital in Birmingham, UK. PATIENTS: All 471 patients registered at
      the adult congenital heart disease clinic were sent the 36 item short form health
      survey (SF-36) to assess their quality of life. Questionnaires were completed by
      276 (58.6%) patients (41.7% men; median (interquartile range) age 31.0 (26.3
      36.0) years, range 16-85 years). RESULTS: Surprisingly, patients deemed
      surgically cured (for example, atrial septal defect repair) had significantly
      poorer quality of life in all domains (all p < 0.05), except for pain, than the
      general population, as determined from population normative data. Patients who
      had received palliative treatment reported quality of life scores similar to
      those who had never required cardiac surgery and to the general population,
      although both patient groups had significantly poorer physical functioning and
      overall general health perception than the general population (all p < 0.01).
      Patients with inoperable conditions had significantly poorer physical functioning
      (all p < 0.01) and overall general health perception (all p < 0.05) than all
      other patients, and significantly worse quality of life in all domains than the
      similarly aged general population. Patients with cyanotic conditions had
      significantly worse quality of life than age and sex matched acyanotic patients
      (all p < 0.01). CONCLUSIONS: Patients with inoperable or cyanotic conditions and,
      paradoxically, those deemed surgically cured, had the poorest quality of life
      among adults with congenital heart disease. However, all adults with congenital
      heart disease had significantly poorer levels of physical functioning and overall
      general health perception then similarly aged people in the general population.

PMID- 12067951
TI  - Congenital bilateral coronary fistulae.

PMID- 12067952
TI  - A new, simple, and accurate method for non-invasive estimation of pulmonary
      arterial pressure.
AB  - OBJECTIVE: To develop and validate a new non-invasive method for the estimation
      of pulmonary arterial pressure (PAP) based on advanced signal processing of the
      second heart sound. DESIGN: Prospective comparative study. SETTING: Referral
      cardiology centre. PATIENTS: This method was first tested in 16 pigs with
      experimentally induced pulmonary hypertension and then in 23 patients undergoing
      pulmonary artery catheterisation. METHODS: The heart sounds were recorded at the
      surface of the thorax using a microphone connected to a personal computer. The
      splitting time interval between the aortic and the pulmonary components of the
      second heart sound was measured using a computer assisted spectral dechirping
      method and was normalised for heart rate. RESULTS: The systolic PAP varied
      between 14-73 mm Hg in pigs and between 20-70 mm Hg in patients. The normalised
      splitting interval was measurable in 97% of the recordings made in pigs and 91%
      of the recordings made in patients. There was a strong relation between the
      normalised splitting interval and the systolic PAP (pigs: r = 0.94, standard
      error of the estimate (SEE) = 5.3 mm Hg; patients: r = 0.84, SEE = 7.8 mm Hg) or
      the mean pulmonary pressure (pigs: r = 0.94, SEE = 4.1 mm Hg; patients: r = 0.85,
      SEE = 5.8 mm Hg). CONCLUSIONS: This study shows that this new non-invasive method
      based on advanced signal processing of the second heart sound provides an
      accurate estimation of the PAP.

PMID- 12067954
TI  - Is early, low level, short term exercise cardiac rehabilitation following
      coronary bypass surgery beneficial? A randomised controlled trial.

PMID- 12067953
TI  - Evaluation of long term cardiotoxicity after epirubicin containing adjuvant
      chemotherapy and locoregional radiotherapy for breast cancer using various
      detection techniques.

PMID- 12067956
TI  - Percutaneous coronary intervention in octogenarians with refractory angina.

PMID- 12067957
TI  - Images in cardiology: Saphenous vein graft aneurysm presenting as an anterior
      mediastinal mass.

PMID- 12067959
TI  - Images in cardiology: Crossed pulmonary arteries, ventricular septal defect, and
      chromosome 22q11 deletion.

PMID- 12067958
TI  - Acquired von Willebrand syndrome in children with patent ductus arteriosus.

PMID- 12067960
TI  - Images in cardiology: Fatal cardiac tamponade in a child due to rupture of a
      mycotic aneurysm.

PMID- 12067961
TI  - Images in cardiology: Intracellular cardiac amyloidosis in familiar amyloid
      polyneuropathy of the Portuguese type.

PMID- 12067962
TI  - Understanding coronary artery disease: tomographic imaging with intravascular
      ultrasound.

PMID- 12067963
TI  - Management of Marfan syndrome.

PMID- 12067964
TI  - Development and structure of the atrial septum.

PMID- 12067965
TI  - Images in cardiology: Imaging of massive pulmonary embolism.

PMID- 12067966
TI  - Images in cardiology: Lipomatous hypertrophy of the interatrial septum.

PMID- 12067968
TI  - 3-deoxy-3-[(18)F]fluorothymidine-positron emission tomography for noninvasive
      assessment of proliferation in pulmonary nodules.
AB  - We investigated whether uptake of the thymidine analogue 3-deoxy-3
      [(18)F]fluorothymidine ([(18)F]FLT) reflects proliferation in solitary pulmonary
      nodules (SPNs). Thirty patients with SPNs were prospectively examined with
      positron emission tomography. Standardized uptake values were calculated for
      quantification of FLT uptake. Histopathology revealed 22 malignant and 8 benign
      lesions. Proliferation was evaluated by Ki-67 immunostaining and showed a mean
      proliferation fraction of 30.9% (range, 1-65%) in malignant SPNs and <5% in
      benign lesions. Linear regression analysis indicated a significant correlation
      between FLT-standardized uptake values and proliferative activity (P < 0.0001; r
      = 0.87). FLT uptake was specific for malignant lesions and may be used for
      differential diagnosis of SPNs, assessment of proliferation, and estimation of
      prognosis.

PMID- 12067969
TI  - Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor
      invasion.
AB  - The gene most commonly altered in human glioblastomas is the epidermalgrowth
      factor receptor (EGFR). We profiled transcripts induced by mutantEGFR to better
      understand its role in tumor progression. The pattern found suggested enhanced
      tumor invasion. The highly induced genes included extracellular matrix
      components, metalloproteases, and a serine protease. We confirmed that mutant
      EGFR did make glioblastoma cells both more motile and invasive using in vitro
      assays. Furthermore, inhibitors of EGFR (OSI-774 and Tyrphostin AG1478)
      selectively down-regulated these molecular effectors in glioblastoma cells,
      eliminating enhanced invasion.

PMID- 12067970
TI  - A preliminary transcriptome map of non-small cell lung cancer.
AB  - We constructed a genome-wide transcriptome map of non-small cell lung carcinomas
      based on gene-expression profiles generated by serial analysis of gene expression
      (SAGE) using primary tumors and bronchial epithelial cells of the lung. Using the
      human genome working draft and the public databases, 25,135 nonredundant UniGene
      clusters were mapped onto unambiguous chromosomal positions. Of the 23,056 SAGE
      tags that appeared more than once among the nine SAGE libraries, 11,156 tags
      representing 7,097 UniGene clusters were positioned onto chromosomes. A total of
      43 and 55 clusters of differentially expressed genes were observed in squamous
      cell carcinoma and adenocarcinoma, respectively. The number of genes in each
      cluster ranged from 18 to 78 in squamous cell carcinomas and from 20 to 165 in
      adenocarcinomas. The size of these clusters varied from 1.8 Mb to 65.5 Mb in
      squamous cell carcinomas and from 1.6 Mb to 98.1 Mb in adenocarcinomas. Overall,
      the clusters with genes over-represented in tumors had an average of 3-4-fold
      increase in gene expression compared with the normal control. In contrast,
      clusters of genes with reduced expression had about 50-65% of the gene expression
      level compared with the normal. Examination of clusters identified in squamous
      cell lung cancer suggested that 9 of 15 clusters with overexpressed genes and 13
      of 28 clusters with underexpressed genes were concordant with previously reported
      cytogenetic, comparative genomic hybridization or loss of heterozygosity studies.
      Therefore, at least a portion of the gene clusters identified via the
      transcriptome map most likely represented the transcriptional or genetic
      alterations occurred in the tumors. Integrating chromosomal mapping information
      with gene expression profiles may help reveal novel molecular changes associated
      with human lung cancer.

PMID- 12067971
TI  - Human cytomegalovirus infection and expression in human malignant glioma.
AB  - Malignant gliomas are the most common primary brain tumors in adults, have no
      known etiology, and are generally rapidly fatal despite current therapies. Human
      cytomegalovirus (HCMV) is beta-herpesvirus trophic for glial cells that
      persistently infects 50-90% of the adult human population. HCMV can be
      reactivated under conditions of inflammation and immunosuppression, and HCMV gene
      products can dysregulate multiple cellular pathways involved in oncogenesis. Here
      we show that a high percentage of malignant gliomas are infected by HCMV and
      multiple HCMV gene products are expressed in these tumors. These data are the
      first to show an association between HCMV and malignant gliomas and suggest that
      HCMV may play an active role in glioma pathogenesis.

PMID- 12067972
TI  - Constitutive activation of signal transducers and activators of transcription 3
      correlates with cyclin D1 overexpression and may provide a novel prognostic
      marker in head and neck squamous cell carcinoma.
AB  - The precise mechanism responsible for the frequent overexpression of cyclinD1 in
      human head and neck squamous cell carcinoma (HNSCC) is not known. In view of the
      fact that signal transducers and activators of transcription 3 (Stat3) is often
      activated in HNSCC cells, we examined the effects of Stat3 on cyclin D1
      expression and cell proliferation in the YCU-H891 HNSCC cell line that displays
      constitutive activation of Stat3. Expression of a dominant negative Stat3
      construct in YCU-H891 cells inhibited proliferation, cyclin D1 promoter activity,
      and cellular levels of cyclin D1 mRNA and protein. The levels of the
      antiapoptotic Bcl-2 and Bcl-X(L) proteins were also inhibited. In 51 primary
      tumor samples from patients with squamous cell carcinoma of the p.o. tongue,
      there was a significant correlation between increased levels of the activated
      form of Stat3, phosphorylated-Stat3, and increased levels of cyclin D1 (P <
      0.0001). Increased tumor levels of phosphorylated-Stat3 were also associated with
      lower survival rates (P < 0.01). This study provides the first evidence that in
      HNSCC, constitutive activation of Stat3 plays a causative role in overexpression
      of cyclin D1, and in clinical studies, Stat3 activation may provide a novel
      prognostic factor. Furthermore, agents that target Stat3 may be useful in the
      treatment of HNSCC.

PMID- 12067973
TI  - Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule-
      stabilizing activity.
AB  - Peloruside A is a novel secondary metabolite isolated from a New Zealand marine
      sponge, Mycale hentscheli, that has potent paclitaxel-like microtubule
      stabilizing activity and is cytotoxic at nanomolar concentrations. Its 16
      membered macrolide ring is similar to that of epothilone, a drug currently under
      clinical investigation as an anticancer agent. Like paclitaxel, peloruside A
      arrests cells in the G(2)-M phase of the cell cycle and induces apoptosis. The
      relatively simple structure of peloruside makes it suitable for the design and
      synthesis of analogues with improved tumor targeting and reduced tumor cross
      resistance.

PMID- 12067974
TI  - Thymidylate synthase promoter polymorphism, interaction with folate intake, and
      risk of colorectal adenomas.
AB  - Thymidylate synthase (TS) is a key enzyme in folate metabolism and the primary
      target of 5-fluorouracil. A repeat polymorphism in the TS promoter enhancer
      region (2rpt versus 3rpt of 28 bp) is associated with decreased expression, and a
      6-bp deletion in the 3'untranslated region may affect RNA stability. We
      investigated the role of TS polymorphisms in a case control study of adenomatous
      polyps (510 cases and 604 polyp-free controls). Multivariate-adjusted odds ratios
      (ORs; 95% confidence interval) for TSER 2rpt/3rpt and 2rpt/2rpt compared with
      3rpt/3rpt were 0.8 (0.6-1.2) and 0.9 (0.6-1.3), respectively. We observed a
      significant gene-nutrient interaction between the TSER polymorphism and folate
      intake: among 3rpt/3rpt individuals (greater expression), folate intake > 440
      microg/day (highest tertile) versus < or =440 microg/day was associated with a 2
      fold decreased risk [ORs 1.0 (reference group) versus 0.5 (0.3-0.9)]. However,
      among 2rpt/2rpt individuals, high folate intake was associated with a 1.5-fold
      increased risk [ORs 0.6 (0.4-0.9) versus 0.9 (0.5-1.5; P for interaction =
      0.03)]. Vitamin B(12) showed a similar trend (P = 0.08). No clear pattern was
      seen with the TS 1494del6 polymorphism. These findings raise questions regarding
      the molecular pathways linking folate metabolism and colorectal carcinogenesis,
      including whether high folate is beneficial in the presence of all metabolic
      genotypes.

PMID- 12067975
TI  - Detection of telomerase inhibitors based on g-quadruplex ligands by a modified
      telomeric repeat amplification protocol assay.
AB  - The telomeric repeat amplification protocol (TRAP) is commonly used to evaluate
      telomerase activity in tissues or cell extracts and also to determine the
      inhibitory properties of small molecules against telomerase. The recent discovery
      of G-quadruplex ligands as potent telomerase inhibitors prompted us to examine
      the accuracy of TRAP to be used to screen such class of molecules. Because of the
      specific feature of the TS primer, TRAP only allows the detection of G-quadruplex
      induced telomerase inhibition after the synthesis of four TTAGGG repeats by
      telomerase and may thus lead to misinterpretations during screening assays. We
      have developed a TRAP-G4 assay that will allow the unambiguous detection of the
      inhibitory properties of a G-quadruplex ligand on telomerase activity and is able
      to discriminate them from other telomerase inhibitors.

PMID- 12067976
TI  - Influence of cytokine gene polymorphisms on the development of prostate cancer.
AB  - Polymorphisms in the promoter regions of cytokine genes may influence prostate
      cancer (PC) development via regulation of the antitumor immune response and/or
      pathways of tumor angiogenesis. PC patients (247) and 263 controls were genotyped
      for interleukin (IL)-1beta-511, IL-8-251, IL-10-1082, tumor necrosis factor-alpha
      308, and vascular endothelial growth factor (VEGF)-1154 single nucleotide
      polymorphisms. Patient control comparisons revealed that IL-8 TT and VEGF AA
      genotypes were decreased in patients compared with controls [23.9 versus 32.3%; P
      = 0.04, odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.44-0.99 and 6.3
      versus 12.9%; P = 0.01, OR = 0.45, 95% CI 0.24-0.86, respectively], whereas the
      IL-10 AA genotype was significantly increased in patients compared with controls
      (31.6 versus 20.6%; P = 0.01, OR = 1.78, 95% CI 1.14-2.77). Stratification
      according to prognostic indicators showed association between IL-8 genotype and
      log prostate-specific antigen level (P = 0.05). These results suggest that single
      nucleotide polymorphisms associated with differential production of IL-8, IL-10,
      and VEGF are risk factors for PC, possibly acting via their influence on
      angiogenesis.

PMID- 12067977
TI  - Critical requirement of BAX for manifestation of apoptosis induced by multiple
      stimuli in human epithelial cancer cells.
AB  - Studies with mouse embryo fibroblasts deficient for the BCL-2 family multidomain
      proapoptotic proteins BAX and BAK have revealed that both of these proteins are
      essential for apoptosis induced by multiple stimuli, suggesting that these
      proapoptotic proteins are functionally overlapping in these cells [M. C. Wei et
      al., Science (Wash. DC), 292: 727-730, 2001; W. X. Zong et al., Genes Dev., 15:
      1481-1486, 2001]. We have determined the effect of several different apoptotic
      stimuli in a Bax-deficient human epithelial cancer cell line (HCT116BaxKO). We
      show that this cell line expresses functional BAK protein and is defective in
      manifestation of apoptosis induced by the BH3-only proteins BIK and BID as well
      as extrinsic stimuli that engage the death receptors, tumor necrosis factor
      receptor, tumor necrosis factor-related apoptosis-inducing ligand receptor, and
      Fas. In addition, this cell line is deficient for apoptosis induced by cytotoxic
      agents such as UV, staurosporine, and thapsigargin that induce either
      mitochondrial or endoplasmic reticulum stress. Our results suggest that BAX plays
      a critical role in the manifestation of apoptosis paradigms induced by multiple
      stimuli in human epithelial cancer cells. Our results also suggest that the
      integrity of BAX may have important consequences in the progression of epithelial
      tumors and in determining the outcome of chemotherapeutic regimens of such
      tumors.

PMID- 12067978
TI  - Ecteinascidin-743 inhibits activated but not constitutive transcription.
AB  - Ecteinascidin-743 (ET-743) is a promising chemotherapeutic agent currently in
      Phase III clinical trials. Previous studies indicated a novel spectrum of
      activity for this agent, including transcriptional inhibition. Initially
      hypothesized to target a single transcription factor (NF-Y), we now show that ET
      743 is a more general inhibitor of activated transcription. Induction of the Sp1
      regulated p21 gene by Trichostatin A (TSA) was blocked by ET-743 at
      concentrations that had minimal effect on uninduced (constitutive) expression.
      Moreover, ET-743 blocked induction of Gal4 fusion proteins by TSA without
      affecting activation mediated by the fusion proteins in the absence of the
      inducer. Finally, microarray analysis of SW620 cells treated with TSA and/or ET
      743 indicated that activation of TSA-responsive promoters was blocked by ET-743
      with little affect on nonresponsive promoters. These results, taken together with
      previous reports, leads us to suggest a mechanism whereby ET-743 is a novel,
      potent, and general inhibitor of activated but not uninduced transcription.

PMID- 12067979
TI  - Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal
      cancers and adenomas.
AB  - Expression of the cadherin family member CDH13 (H-cadherin) is reduced in several
      human tumors, and it has been hypothesized that this gene functions as a tumor
      suppressor gene. Previously, we reported that the 5' region of CDH13 is
      frequently methylated in breast and lung cancers. Here we confirmed the promoter
      activity of 5' region of CDH13 by luciferase assay and examined its aberrant
      methylation in colorectal cancers, cell lines, and adenomas. Methylation status
      was investigated by methylation-specific PCR (MSP) and by bisulfite DNA
      sequencing of cloned DNA of PCR amplicons. In cell lines, we examined the
      correlation between methylation status and mRNA expression by reverse
      transcription-PCR. Aberrant methylation of CDH13 was present in 7 of 13 (54%)
      cell lines, and expression was absent in 6 of 13 (46%) cell lines. CDH13
      expression was present in six cell lines that showed only the unmethylated form
      by MSP and in one cell line that showed both the methylated and unmethylated
      forms. Treatment with 5-aza-2'-deoxycytidine restored CDH13 expression in
      methylated cell lines. In surgically resected samples, 17 of 35 (49%) cases of
      primary colorectal cancer, 2 of 33 (6%) cases of corresponding nonmalignant
      colorectal mucosa, and 8 of 19 (42%) adenomas were methylated. Sequence data
      after bisulfite treatment indicated that primary cancers and two cell lines with
      loss of expression were highly methylated compared with nonmalignant colorectal
      epithelial cells, especially at the attachment sites of primers for MSP, although
      there was heterogeneity in methylation status. Our results suggest that CDH13
      expression is frequently silenced by aberrant methylation in colorectal cancers
      and adenomas and that methylation of CDH13 commences at an early stage of
      multistep colorectal tumorigenesis.

PMID- 12067980
TI  - Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance
      (MDR1) gene.
AB  - The microenvironment of rapidly growing tumors is associated with increased
      energy demand and diminished vascular supply, resulting in focal areas of
      prominent hypoxia. A number of hypoxia-responsive genes have been associated with
      growing tumors, and here we demonstrate that the multidrug resistance (MDR1) gene
      product P-glycoprotein, a Mr approximately 170,000 transmembrane protein
      associated with tumor resistance to chemotherapeutics, is induced by ambient
      hypoxia. Initial studies using quantitative microarray analysis of RNA revealed
      an approximately 7-fold increase in MDR in epithelial cells exposed to hypoxia
      (pO(2) 20 torr, 18 h). These findings were further confirmed at the mRNA and
      protein level. P-Glycoprotein function was studied by analysis of verapamil
      inhibitable efflux of digoxin and rhodamine 123 in intact T84 cells and revealed
      that hypoxia enhances P-glycoprotein function by as much as 7 +/- 0.4-fold over
      normoxia. Subsequent studies confirmed hypoxia-elicited MDR1 gene induction and
      increased P-glycoprotein expression in nontransformed, primary cultures of human
      microvascular endothelial cells, and analysis of multicellular spheroids
      subjected to hypoxia revealed increased resistance to doxorubicin. Examination of
      the MDR1 gene identified a binding site for hypoxia inducible factor-1 (HIF-1),
      and inhibition of HIF-1 expression by antisense oligonucleotides resulted in
      significant inhibition of hypoxia-inducible MDR1 expression and a nearly complete
      loss of basal MDR1 expression. Studies using luciferase promoter constructs
      revealed a significant increase in activity in cells subjected to hypoxia, and
      such hypoxia inducibility was lost in truncated constructs lacking the HIF-1 site
      and in HIF-1 binding site mutants. Extensions of these studies also identified a
      role for Sp1 in this hypoxia response. Taken together, these data indicate that
      the MDR1 gene is hypoxia responsive, and such results may identify hypoxia
      elicited P-glycoprotein expression as a pathway for resistance of some tumors to
      chemotherapeutics.

PMID- 12067981
TI  - Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal
      differentiation and reduces mouse skin tumorigenesis.
AB  - Nonsteroidal anti-inflammatory drugs are widely reported to inhibit
      carcinogenesis in humans and in rodents. These drugs are believed to act by
      inhibiting one or both of the known isoforms of cyclooxygenase (COX). However,
      COX-2, and not COX-1, is the isoform most frequently reported to have a key role
      in tumor development. Here we report that homozygous deficiency of either COX-1
      or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model.
      Reduced tumorigenesis was observed even though the levels of stable 7,12
      dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX
      deficient mice compared with wild-type mice. The premature onset of keratinocyte
      terminal differentiation appeared to be the cellular event leading to the reduced
      tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the
      commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20
      fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2
      deficient mice, respectively, than in wild-type mice. Papillomas on the COX
      deficient mice also displayed the premature onset of keratinocyte terminal
      differentiation. However, loricrin, a late marker of epidermal differentiation,
      was not significantly altered, suggesting that it was the early stages of
      keratinocyte differentiation that were primarily affected by COX deficiency.
      Because keratin 5, a keratin associated with basal cells, was detected
      differently in papillomas of COX-1-deficient as compared with COX-2-deficient
      mice, it appears that the isoforms do not have identical roles in papilloma
      development. Interestingly, apoptosis, a cellular process associated with
      nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not
      significantly altered in the epidermis or in papillomas of the COX-deficient
      mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and
      we propose that the absence of either isoform causes premature terminal
      differentiation of initiated keratinocytes and reduced tumor formation.

PMID- 12067982
TI  - A critical role for ras-mediated, epidermal growth factor receptor-dependent
      angiogenesis in mouse skin carcinogenesis.
AB  - Epidermal growth factor receptor (EGFR) plays a critical role in epidermal
      biology. Abnormal EGFR function has been described in epithelial tumors including
      those induced by two-stage chemical carcinogenesis in mouse skin. A large body of
      evidence indicates that in this model, activation of Ha-ras is the critical event
      in papilloma formation, a process that involves epidermal proliferation and
      stroma remodeling, which includes angiogenesis. This study reports that activated
      Ha-ras results in a dramatic induction of EGFR in epidermal tumor cells and
      provides experimental evidence that EGFR signaling is responsible for Ha-ras
      dependent vascular endothelial growth factor (VEGF) induction, as well as for the
      repression of other angiogenic factors such as angiopoietin 1. The pivotal role
      of functional EGFR in throwing the angiogenic switch necessary for tumor growth
      was confirmed by s.c. injection of immunodeficient mice with epidermal tumor
      cells carrying a dominant negative (dn) EGFR and by in vivo chemical skin
      carcinogenesis assays in transgenic mice expressing the same dn EGFR form in the
      epidermis. Immunohistochemical analysis of the tumors obtained by both ex vivo
      and in vivo approaches showed that dn EGFR expression abolished the changes in
      blood vessels that occurred during tumor progression. A strong reduction of VEGF
      expression in dn EGFR tumors appears to be the key event responsible for
      angiogenesis and tumor growth suppression. The apoptotic rate was increased, and
      Akt activity was decreased, suggesting that impaired nutrient and oxygen supply
      might contribute to diminished cell survival in dn EGFR tumors. Support for this
      mechanism is provided by the fact that the ectopic expression of VEGF in dn EGFR
      expressing tumor cell lines restored tumor growth capacity. Although ras
      activation might suffice for epidermal transformation and the stroma-remodeling
      events of tumor induction, such effects may not be operative without a functional
      upstream EGFR. It is tempting to speculate that EGFR family members may function
      as angiogenic regulators in other epithelial tumors such as those of the colon,
      breast, and prostate, reinforcing their value as targets for therapeutic
      intervention.

PMID- 12067984
TI  - Prognostic significance of the metastasis-associated protein osteopontin in human
      breast cancer.
AB  - The adhesive glycophosphoprotein (OPN) is capable of inducing metastasis in
      rodent models ofbreast cancer. We now show that a monoclonal antibody to rat OPN
      recognizes specifically human OPN using Western blotting techniques andused it to
      assess the prognostic significance of OPN in primary tumors of a group of 333
      patients treated between 1976 and 1982 for operable stage I and stage II breast
      cancer. The antibody stains immunocytochemically normal breast tissue weakly but
      pregnant/lactating tissue and 66% of the carcinomas strongly, leaving the
      remaining 34% as negatively stained. In addition to the carcinoma cells, some
      host reactive stromal cells, macrophages, lymphocytes, and blood vessels are also
      stained, but these have been excluded in the following analyses. There is a
      significant association of staining of carcinomas for OPN with some tumor
      variables reported previously to be associated with patient outcome: high
      histological grade (P = 0.024), staining for c-erbB-3 (P < 0.001), p53 (P =
      0.014), pS2 (P = 0.025), and borderline significance for progesterone receptor (P
      = 0.089). The association of staining for OPN with survival times of the patients
      has been evaluated using life tables over 14-20 years of follow-up (mean 16
      years) and analyzed using generalized Wilcoxon statistics. Of the patients who
      have been classified as OPN-negative, 94% are alive, but only 26% of those
      classified as OPN-positive are alive after 19 years of follow-up. This
      association is highly significant (P < 0.0001); the former have a median survival
      of >228 months and the latter 68 months. When the patients are divided into
      separate classes based on the percentage of carcinoma cells staining for OPN, the
      five classes show a progressive decrease in survival with increasing percentage
      of stained carcinoma cells, and this association is also highly significant (P <
      0.0001). Other tumor variables that show a significant association with patient
      survival times in this group of patients include nodal status, tumor size,
      histological grade, staining for c-erbB-2, estrogen receptor alpha, or p53.
      Analysis of the association of patients with carcinomas staining for OPN and
      their survival in subgroups defined by these tumor variables shows that positive
      staining for OPN in each subgroup is associated with poorer survival. There is
      little difference in patient survival times in the OPN-negative group of patients
      with or without any of the other tumor variables examined. Multivariate
      regression analysis for 202 patients shows that staining for OPN is most highly
      correlated with patients' deaths (P < 0.0001), but involved lymph nodes (P =
      0.0007), fixed tumors (P = 0.0008), and staining for estrogen receptor alpha (P =
      0.008) are also significant independent prognostic variables with that for c-erbB
      2 being of borderline significance (P = 0.060). These results suggest that in
      this group of patients, the presence of the metastasis-associated protein OPN is
      tightly correlated with patient demise.

PMID- 12067983
TI  - A phase I pharmacokinetic and translational study of the novel vascular targeting
      agent combretastatin a-4 phosphate on a single-dose intravenous schedule in
      patients with advanced cancer.
AB  - Combretastatin A-4 phosphate (CA4P) is a novel antitumor vascular targeting
      agent, the first agent of this class of compounds to enter the clinic. We
      performed a Phase I trial to determine the maximum-tolerated dose, safety, and
      pharmacokinetic profile of CA4P on a single-dose i.v. schedule. We also obtained
      preliminary data on its effect on tumor blood flow using dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI) techniques and cell adhesion
      molecules at the higher-dose levels. Twenty-five assessable patients with
      advanced cancer received a total of 107 cycles over the following dose escalation
      schema: 18, 36, 60, 90 mg/m(2) as a 10-min infusion and 60 mg/m(2) as a 60-min
      infusion at 3-week intervals. There was no significant myelotoxicity, stomatitis,
      or alopecia. Tumor pain was a unique side effect, which occurred in 10% of
      cycles, and there were four episodes of dose-limiting toxicity at dosages > or
      =60 mg/m(2), including two episodes of acute coronary syndrome. Pharmacokinetics
      revealed rapid dephosphorylation of the parent compound (CA4P) to combretastatin
      A4 (CA4), with a short plasma half-life (approximately 30 min). A significant (P
      < 0.03) decline in gradient peak tumor blood flow by DCE-MRI in six of seven
      patients treated at 60 mg/m(2) was observed. A patient with anaplastic thyroid
      cancer had a complete response and is alive 30 months after treatment. The
      toxicity profile is consistent with a drug that is "vascularly active" and devoid
      of traditional "cytotoxic" side effects. Dosages < or =60 mg/m(2) as a 10-min
      infusion define the upper boundary of the maximum-tolerated dose.

PMID- 12067985
TI  - Association of interferon regulatory factor-1, nucleophosmin, nuclear factor
      kappaB, and cyclic AMP response element binding with acquired resistance to
      Faslodex (ICI 182,780).
AB  - To identify genes associated with survival from antiestrogens, both serial
      analysis of geneexpression and gene expression microarrays were used to explore
      the transcriptomes of antiestrogen-responsive (MCF7/LCC1) and -resistant
      variants(MCF7/LCC9) of the MCF-7 human breast cancer cell line. Structure of the
      gene microarray expression data was visualized at the top level using a novel
      algorithm that derives the first three principal components,fitted to the
      antiestrogen-resistant and -responsive gene expression data, from Fisher's
      information matrix. The differential regulation of several candidate genes was
      confirmed. Functional studies of the basal expression and endocrine regulation of
      transcriptional activation of implicated transcription factors were studied using
      promoter-reporter assays. The putative tumor suppressor interferon regulatory
      factor-1 is down-regulated in resistant cells, whereas its nucleolar
      phosphoprotein inhibitor nucleophosmin is up-regulated. Resistant cells also up
      regulate the transcriptional activation of cyclic AMP response element (CRE)
      binding and nuclear factor kappaB (NFkappaB) while down-regulating epidermal
      growth factor receptor protein expression. Inhibition of NFkappaB activity by ICI
      182,780 is lost in resistant cells, but CRE activity is not regulated by ICI
      182,780 in either responsive or resistant cells. Parthenolide, a potent and
      specific inhibitor of NFkappaB, inhibits the anchorage-dependent proliferation of
      antiestrogen-resistant but not antiestrogen-responsive cells. This observation
      implies a greater reliance on their increased NFkappaB signaling for
      proliferation in cells that have survived prolonged exposure to ICI 182,780.
      These data from serial analysis of gene expression and gene microarray studies
      implicate changes in a novel signaling pathway, involving interferon regulatory
      factor-1, nucleophosmin, NFkappaB, and CRE binding in cell survival after
      antiestrogen exposure. Cells can up-regulate some estrogen-responsive genes while
      concurrently losing the ability of antiestrogens to regulate their expression.
      Signaling pathways that are not regulated by estrogens also can be up-regulated.
      Thus, some breast cancer cells may survive antiestrogen treatment by bypassing
      specific growth inhibitory signals induced by antagonist-occupied estrogen
      receptors.

PMID- 12067986
TI  - An E2F-responsive replication-selective adenovirus targeted to the defective cell
      cycle in cancer cells: potent antitumoral efficacy but no toxicity to normal
      cell.
AB  - To improve the transduction and distribution of adenovirus in a tumor mass, we
      generated an adenovirus to selectively replicate in tumors. We hypothesized that
      after infection the replicating adenovirus would spread throughout the tumor mass
      and cause direct oncolysis of tumor cells. E2F transcription factors are critical
      regulators of cell growth and are often overexpressed in cancer cells because of
      the frequent aberrations in the pRb/E2F/p16(INK4a) pathway. As a result, a
      majority of tumor cells exist in a high proliferative state. E2F-1 is a
      transcription factor that activates its own transcription and that of other genes
      involved in the G(1) to S transition phase of the cell cycle. We constructed an
      adenovirus (Ad(E2F-1(RC)) so that E1A expression and viral replication were under
      the control of the human E2F-1 promoter element. AdE2F-1(RC) virus replicated as
      efficiently as the wild-type adenovirus and caused extensive cell killing in a
      panel of tumor cells in vitro. In contrast, nonproliferating normal epithelial,
      fibroblast, and endothelial cells, which express no E2F-1, were not able to
      support AdE2F-1(RC) replication. In animal studies, different dosing regimens of
      AdE2F-1(RC) administered to flank xenografts of ovarian and lung cancers led to a
      significant therapeutic advantage often surpassing that seen in animals treated
      with the wild-type adenovirus. This novel selectively replicating adenovirus
      offers a promising treatment platform for a variety of cancers of which the
      hallmark is uncontrolled cell growth.

PMID- 12067987
TI  - Lack of promotion of estrogen-dependent mammary gland tumors in vivo by an
      isopropanolic Cimicifuga racemosa extract.
AB  - Cimicifuga racemosa (CR) is widely used in the treatment of menopausal symptoms.
      Mechanistic studies suggest that unlike hormone-replacement therapy, CR does not
      stimulate estrogen-receptor positive breast cancer cells. To evaluate CR safety,
      we performed an in vivo investigation of a clinically tested isopropanolic CR
      extract. Mammary tumors were induced in Sprague Dawley rats (n = 75) by the
      application of 7,12-dimethylbenz[a]anthracene. Five to nine weeks later, the
      animals were ovariectomized, allowed to recover, and administered daily doses of
      CR extract (0.714, 7.14, or 71.4 mg/kg body weight per day) or control substances
      (estrogen/positive control: 450 microg/kg/day mestranol; or CR vehicle/negative
      control). The animals were sacrificed 6 weeks later, and tumor number, size,
      plasma hormone levels, and the weight of estrogen-sensitive organs were analyzed.
      In contrast to mestranol treatment, CR treatment did not stimulate cancerous
      growth. There were no significant differences in tumor number or size between the
      CR groups and the vehicle control. Likewise, prolactin, follicle-stimulating
      hormone, and luteinizing hormone levels and organ weights and endometrial
      proliferation were unaffected. The lack of mammary tumor-stimulating effects of
      this extract is of great significance in establishing the safety of CR extracts
      for treatment of menopausal symptoms in women with a history of breast cancer in
      which hormone-replacement therapy is contraindicated.

PMID- 12067989
TI  - Anti-4-1BB monoclonal antibody enhances rejection of large tumor burden by
      promoting survival but not clonal expansion of tumor-specific CD8+ T cells.
AB  - Anti-4-1BB monoclonal antibody (mAb) has been shown to induce antitumor immunity
      by a CD4/CD8-dependent mechanism, but its direct effect on tumor-specific CD8+ T
      cells in tumor rejection is unclear. Here we used transgenic CD8+ T cells against
      the unmutated tumor rejection antigen P1A to analyze whether this mAb can promote
      CD8+ T-cell function against large tumors in the absence of CD4+ T-helper cells.
      RAG-2(-/-) mice were challenged with P1A-expressing plasmacytoma J558. Once tumor
      size reached a diameter of 0.85-1.75 cm, mice were treated with P1A-specific CD8+
      CTL (P1CTL) in conjunction with anti-4-1BB mAb or control IgG. All of the mice
      showed a partial regression of tumor, but mice treated with anti-4-1BB mAb
      exhibited markedly enhanced tumor rejection, delayed tumor progression, and
      prolonged survival. Correspondingly, we observed a substantial increase in the
      number of P1CTL in anti-4-1BB mAb-treated mice. Surprisingly, anti-4-1BB mAb did
      not accelerate division of the tumor-specific CD8+ T cells, and the increase in
      tumor-specific T-cell number was due to reduced activation-induced cell death.
      These results indicate that anti-4-1BB mAb can promote CD8+ T cell-mediated
      protection against large tumors in the absence of CD4+ T-cell help by promoting
      P1CTL survival without increasing initial clonal expansion.

PMID- 12067988
TI  - Interferon stimulated gene 15 constitutively produced by melanoma cells induces e
      cadherin expression on human dendritic cells.
AB  - The immunobiology of tumor-infiltrating dendritic cells (DCs) can be strongly
      influenced by the cytokine environment present in the malignant tissue. We have
      previously identified discrete melanoma lines, inducing E-cadherin expression on
      monocyte-derived DCs in vitro. We demonstrate here that this effect, independent
      of cell contact, is not inducible in the presence of tumor lysates and requires
      the constitutive expression of IFN stimulated gene 15 (ISG15) by malignant cells.
      High-density oligonucleotide arrays were used to investigate the expression
      pattern of 7000 genes in RNA from two melanoma cell clones competent for E
      cadherin induction and two clones devoid of DC-modulating capacity. A total of 13
      genes encoding soluble proteins were expressed at higher magnitude in melanomas
      able to induce E-cadherin expression on DCs. Combining those data with
      quantitative protein assays, we could narrow our investigation down to three
      factors: the chemokine CCL5 and the cytokines ISG15 and type I IFNs. Strikingly,
      >7 ng/ml of ISG15 could be detected in the corresponding melanoma-conditioned
      medium and induction of E-cadherin on DCs failed in the presence of antibodies
      neutralizing ISG15 protein. Most importantly, strong cytoplasmic expression of
      ISG15 was detected by immunohistochemistry in the original tumor specimen from
      which the melanoma cell lines under investigation were derived. These data
      describe a novel property of ISG15 targeting induction of E-cadherin on DCs and
      possibly influencing their migratory behavior.

PMID- 12067990
TI  - Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping,
      comparative genomic hybridization, and expression microarrays.
AB  - Analysis of ovarian carcinomas has shown that karyotypes are often highly
      abnormal and cannot be identified with certainty by conventional cytogenetic
      methods. In this study, 17 tumors derived from 13 patients were analyzed by a
      combination of spectral karyotyping (SKY), comparative genomic hybridization
      (CGH), and expression microarrays. Within the study group, a total of 396
      chromosomal rearrangements could be identified by SKY and CGH analysis. When the
      distribution of aberrations was normalized with respect to relative genomic
      length, chromosomes 3, 8, 11, 17, and 21 had the highest frequencies. Parallel
      microarray expression studies of 1718 human cDNAs were used to analyze expression
      profiles and to determine whether correlating gene expression with chromosomal
      rearrangement would identify smaller subsets of differentially expressed genes.
      Within the entire set of samples, microarray expression analysis grouped together
      poorly differentiated tumors irrespective of histological subtype. For three
      patients, a comparison between genomic alterations and gene expression pattern
      was performed on samples of primary and metastatic tumors. Their common origin
      was demonstrated by the close relationship of both the SKY and CGH karyotypes and
      the observed profiles of gene expression. In agreement with the pattern of
      genomic imbalance observed for chromosome 3 in ovarian cancer, the relative
      expression profile with respect to a normal ovary exhibited a contiguous pattern
      of reduced expression of genes mapping to the 3p25.5-3p21.31 and increased
      expression of genes from 3q13.33-3q28. This study demonstrates that SKY, CGH, and
      microarray analysis can in combination identify significantly smaller subsets of
      differentially expressed genes for future studies.

PMID- 12067991
TI  - Identification of unstable sequences within the common fragile site at 3p14.2:
      implications for the mechanism of deletions within fragile histidine triad
      gene/common fragile site at 3p14.2 in tumors.
AB  - The FRA3B, at 3p14.2, lies within the fragile histidine triad (FHIT) gene and is
      the most highly expressed of the common fragile sites observed when DNA
      replication is perturbed by aphidicolin. Common fragile sites are highly unstable
      regions of the genome. Large intragenic deletions within FHIT, localized within
      the FRA3B sequences, have been identified in a variety of tumor cells. To
      characterize the FRA3B deletions in tumor cells and identify FRA3B sequences that
      are required for fragile site induction, we used microcell-mediated chromosome
      transfer to isolate hybrid cell clones that retain chromosome 3 homologues with
      various deletions within FRA3B. Detailed molecular mapping of the FHIT/FRA3B
      locus in the resultant hybrid cells revealed a complex pattern of instability
      within FRA3B. Each tumor cell line contained multiple chromosome 3 homologues
      with variable deletion patterns, often with discontinuous deletions, suggesting
      that the process of breakage and repair within FRA3B is an ongoing one. By
      comparing the approximate location of the breakpoints in the hybrid clones, we
      identified 11 recurring breakpoint/repair regions within the FRA3B. A comparison
      of the frequency of breaks/gaps within FRA3B in the hybrid clones with various
      deletions of FRA3B sequences revealed that the loss of FRA3B sequences does not
      reduce the overall rate of breakage and instability within the remaining FRA3B
      sequences. The majority of breaks occurred in the proximal portion of the FRA3B,
      in a 300-kb interval between exon 4 and the proximal 50 kb of intron 5. Our
      observations suggest that there is no single sequence within the FRA3B that
      influences breakage or recombination within this region; however, we cannot rule
      out the presence of multiple "hot spots" within the FHIT/FRA3B locus. Together,
      the results suggest that factors other than the DNA sequence per se are
      responsible for the formation of DNA breaks/gaps.

PMID- 12067992
TI  - Evaluation of microsatellite instability and immunohistochemistry for the
      prediction of germ-line MSH2 and MLH1 mutations in hereditary nonpolyposis colon
      cancer families.
AB  - Forty-eight hereditary nonpolyposis colorectal carcinoma (HNPCC) families for
      which a tumor sample was available were evaluated for the presence of germ-line
      mutations in MSH2 and MLH1, tumor microsatellite instability (MSI), and where
      possible, expression of MSH2 and MLH1 in tumors by immunohistochemistry. Fourteen
      of 48 of the families had a germ-line mutation in either MSH2 or MLH1 that could
      be detected by genomic DNA sequencing, and 28 of 48 of the families had MSI-H
      tumors. Four additional families showed loss of expression of MSH2, and one
      additional family showed loss of expression of MLH1 but did not have germ-line
      mutations in MSH2 or MLH1 that could be detected by DNA sequencing. MSI-H, as
      defined using the National Cancer Institute recommended five-microsatellite
      panel, had a 100% sensitivity for identifying samples having MSH2 or MLH1
      mutations or loss of expression. In contrast, loss of MSH2 and MLH1 expression
      did not identify all samples having germ-line mutations in MSH2 or MLH1, because
      in five cases, a mutant protein product was expressed that could be detected by
      IHC. A combination of the Bethesda criteria for HNPCC and an MSI-H phenotype
      defined the smallest number of cases having all of the germ-line MSH2 and MLH1
      mutations that could be detected by DNA sequencing.

PMID- 12067993
TI  - Artificial neural networks and gene filtering distinguish between global gene
      expression profiles of Barrett's esophagus and esophageal cancer.
AB  - cDNAmicroarrays, combined with bioinformatics analyses, are becomingincreasingly
      used in current medical research. Existing analytic methods,particularly those
      that are unsupervised, often have difficulty recognizing subtle differences among
      predefined subgroups. In contrast, supervised methods, such as Artificial Neural
      Networks (ANNs), are able to recognize subtly different biological entities. We
      applied ANNs in a proof-of-principle study of cDNA microarray data in esophageal
      cancer (CA) and premalignancy. cDNA microarrays, each containing 8064 clones,
      were hybridized to RNAs from 22 esophageal lesions, including 14 Barrett's
      esophagus (BA) metaplasias and 8 esophageal carcinomas (3 squamous cell
      carcinomas and 5 adenocarcinomas). Scanned cDNA microarray data were analyzed
      using the bioinformatics software Cluster/TreeView, Significance Analysis of
      Microarrays (SAM), and ANNs. Cluster analysis based on all 8064 clones on the
      microarrays was unable to correctly distinguish BA specimens from CA specimens.
      SAM then selected 160 differentially expressed genes between Barrett's and
      cancer. Cluster analysis based on this reduced set still misclassified 2
      Barrett's as cancers. The ANN was trained on 12 samples and tested against the
      remaining 10 samples. Using the 160 selected genes, the ANN correctly diagnosed
      all 10 samples in the test set. Finally, the 160 genes selected by SAM may merit
      further study as biomarkers of neoplastic progression in the esophagus, as well
      as in elucidating pathological mechanisms underlying BA and CA.

PMID- 12067995
TI  - beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric
      cancer.
AB  - Studies of Wnt activation in gastric cancer have yielded conflicting results. The
      goals of this study were to determine the frequency of Wnt pathway activation and
      beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were
      examined for beta-catenin expression by immunostaining and dissected using laser
      capture microscopy to obtain DNA from those tumors with nuclear beta-catenin.
      Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric
      cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified
      and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no
      mutations were detected in 19 tumors negative for beta-catenin nuclear staining
      (P < 0.05). Most mutations were adjacent to or abolished known regulatory
      phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric
      cancer that display nuclear beta-catenin. These results suggest that Wnt pathway
      activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.

PMID- 12067994
TI  - The RASSF1A tumor suppressor gene is inactivated in prostate tumors and
      suppresses growth of prostate carcinoma cells.
AB  - We analyzed expression status of the recently identified tumor suppressor
      geneRASSF1A in primary prostate carcinomas and in prostate cell lines. We found
      complete methylation of the RASSF1A promoter in 63% of primary microdissected
      prostate carcinomas (7 of 11 samples). The remaining 4 samples (37%) were
      partially methylated, possibly because of contamination with normal cells. No
      promoter methylation was observed in matching normal prostate tissues. High
      levels of RASSF1A transcript and no methylation of RASSF1A promoter were found in
      explanted primary normal prostate epithelial and stromal cells. Complete
      silencing and methylation of RASSF1A promoter was observed in five widely used
      prostate carcinoma cell lines, which acquired the ability to grow in culture
      spontaneously, including LNCaP, PC-3, ND-1, DU-145, 22Rv1, and one primary
      prostate carcinoma immortalized by overexpression of the human telomerase
      catalytic subunit (RC-58T/hTERT). However, no silencing of RASSF1A was found in
      four other prostate carcinoma cell lines, which were adapted for cell culture
      after transformation with human papillomaviral DNA. Suppression of cell growth in
      vitro was demonstrated after the reintroduction of RASSF1A-expressing construct
      into LNCaP prostate carcinoma cells. Our data implicate the RASSF1A gene in human
      prostate tumorigenesis.

PMID- 12067996
TI  - Omomyc, a potential Myc dominant negative, enhances Myc-induced apoptosis.
AB  - The Myc basic helix-loop-helix zipper domain determines dimerization with Max and
      binding to the DNA E-box, both of which play a critical role in Myc regulation of
      growth, proliferation, tumorigenesis, and apoptosis. The mutant basic helix-loop
      helix zipper domain, Omomyc, dimerizes with Myc, sequestering it in complexes
      unable to bind the E-box, and so acting as a potential dominant negative.
      Consistent with this, Omomyc reverses Myc-induced cytoskeletal disorganization in
      C2C12 myoblasts. Surprisingly, however, Omomyc strongly potentiates Myc-induced
      apoptosis in a manner dependent on Myc expression level. Expression analysis of
      known Myc target genes indicates that Omomyc inhibits transcriptional activation
      but enhances repression. These findings suggest that Omomyc can selectively
      trigger apoptosis in cells overexpressing Myc, possibly through the
      transcriptional repression of specific genes.

PMID- 12067997
TI  - Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis.
AB  - To reach the biological alterations that characterize cancer, the genome of tumor
      cells must acquire increased mutability resulting from a malfunction of a network
      of genome stability systems, e.g., cell cycle arrest, DNA repair, and high
      accuracy of DNA synthesis during DNA replication. Numeric chromosomal imbalance,
      referred to as aneuploidy, is the most prevalent genetic changes recorded among
      many types of solid tumors. We report here that ectopic expression in cells of
      DNA polymerase beta, an error-prone enzyme frequently over-regulated in human
      tumors, induces aneuploidy, an abnormal localization of the centrosome-associated
      gamma-tubulin protein during mitosis, a deficient mitotic checkpoint, and
      promotes tumorigenesis in nude immunodeficient mice. Thus, we find that
      alteration of polymerase beta expression appears to induce major genetic changes
      associated with a malignant phenotype.

PMID- 12067998
TI  - Genotoxic exposure is associated with alterations in glucose uptake and
      metabolism.
AB  - Recent observations suggest that growth factor withdrawal can promote cell death
      in part through modulation of basic cellular bioenergetic pathways, including
      inhibition of glucose uptake and glycolytic metabolism. Whether DNA damage
      initiated cell death pathways also involve bioenergetic deregulation has not been
      studied previously. Subtractive suppressive hybridization was used to identify
      changes in gene expression in murine cells after exposure to genotoxic stimuli,
      including cisplatin, etoposide, and gamma-radiation. Among the genes identified
      in this screen were several that regulate glycolytic metabolism. Enzymes that
      catalyze key regulatory steps of glycolysis, including hexokinase,
      phosphofructokinase, and pyruvate kinase, appeared to be coordinately down
      regulated by genotoxic exposure. Northern blotting confirmed that these changes
      in gene expression occur within 4 h of exposure to several DNA-damaging agents.
      Genotoxic exposure was found to similarly inhibit expression of both glut-1 and
      glut-3, genes that encode critical regulators of glucose uptake. Direct
      measurement of glycolytic rate and of oxygen consumption confirmed that genotoxic
      exposure resulted in suppression of both anaerobic and aerobic metabolism. Many
      of these metabolic changes mimic those observed after growth factor withdrawal.
      Together, these observations suggest that multiple apoptotic triggers, including
      growth factor withdrawal and genotoxic exposure, suppress cellular bioenergetic
      pathways. Mitochondrial responses to the resulting rapid decrease in metabolic
      substrates may play an important role in initiation of apoptotic cell death.

PMID- 12067999
TI  - Frequencies of tetramer+ T cells specific for the wild-type sequence p53(264-272)
      peptide in the circulation of patients with head and neck cancer.
AB  - Immunization with wild-type sequence (wt) p53 epitopes represents a novel
      therapeutic strategy for cancer patients with tumors accumulating mutant p53. To
      evaluate usefulness of p53-derived peptides as future cancer vaccines,
      frequencies of wt p53(264-272) peptide-specific CD8+ T cells were determined in
      the peripheral circulation of patients with squamous cell carcinoma of the head
      and neck (SCCHN). T cells of 30 HLA-A2.1+ patients and 31 HLA-A2.1+ healthy
      individuals were evaluated by multicolor flow cytometry analysis using peptide
      HLA-A2.1 complexes (tetramers). T cells specific for an influenza matrix peptide
      (a model recall antigen) or an HIV reverse transcriptase peptide (a model novel
      antigen) were studied in parallel. Patients with SCCHN had a significantly higher
      mean frequency of CD8+ T cells specific for wt p53(264-272) than normal donors (P
      = 0.0041). Surprisingly, the frequency of epitope-specific T cells in the
      circulation of patients did not correlate with p53 accumulation in the tumor. In
      patients whose tumors had normal p53 expression or had p53 gene mutations
      preventing presentation of this epitope, high frequencies of wt p53(264-272)
      specific CD8+ T cells were found, of which many were memory T cells. In contrast,
      patients whose tumors accumulated p53 had low frequencies of wt p53(264-272)
      specific CD8+ T cells, which predominantly had a naive phenotype and were unable
      to proliferate ex vivo in response to the epitope, as reported by us previously
      (T. K. Hoffmann, J. Immunol., 165: 5938-5944, 2000). This seemingly contradictory
      relationship between the high frequency of epitope-specific T cells and wt p53
      expression in the tumor suggests that other factors may contribute to the
      observed anti-p53 responses. Human papillomavirus-16 E6/E7 expression is common
      in SCCHN, and E6 is known to promote presentation of wt p53 epitopes. Although
      human papillomavirus-16 E6/E7 expression was detected in 46% of the tumors, it
      did not correlate with the frequency of wt p53(264-272)-specific CD8+ T cells or
      with p53 expression in the tumor. These findings emphasize the complexity of
      interactions between the tumor and the host immune system, and, thus, have
      particularly important implications for future p53-based immunization strategies.

PMID- 12068000
TI  - Insulin-like growth factor binding protein-3 inhibits the growth of non-small
      cell lung cancer.
AB  - Insulin-like growth factors (IGFs) have mitogenic and antiapoptotic properties
      and have been implicated in the development of lung cancer. The effects of IGFs
      are modulated by insulin-like growth factor binding proteins (IGFBPs). This study
      explored the effects of IGFBP-3 on non-small cell lung cancer (NSCLC) cells after
      infection with an adenovirus constitutively expressing IGFBP-3 under the control
      of the cytomegalovirus promoter (Ad5CMV-BP3). We found that IGFs, especially IGF
      I, stimulated the growth of NSCLC cells, and Ad5CMV-BP3 suppressed this IGF-I
      induced NSCLC cell growth. We also found that the clonogenicity of H1299 cells in
      soft agar was markedly reduced by Ad5CMV-BP3. Furthermore, direct injection of
      Ad5CMV-BP3 into H1299 NSCLC xenografts s.c. established in athymic nude mice
      induced massive destruction of the tumors. Ad5CMV-BP3 did not induce detectable
      cytotoxicity on normal human bronchial epithelial cells, suggesting therapeutic
      efficacy of this virus. Ad5CMV-BP3 infection was accompanied by apoptotic cell
      death in vitro as detected by flow cytometry, DNA fragmentation analysis, and
      Western blot analysis on the expression of Bcl-2 and on the cleavage of poly(ADP
      ribose) polymerase, a substrate of caspase 3. Immunofluorescence confocal
      microscopy was also used to show the apoptotic effect of Ad5CMV-BP3 in H1299
      tumors established in nude mice. These findings indicated that IGFBP-3 was a
      potent inducer of apoptosis in NSCLC cells in vitro and in vivo. To delineate the
      underlying mechanism, we examined the effect of IGFBP-3 on Akt/protein kinase B
      and glycogen synthase kinase-3beta, downstream mediators of the
      phosphatidylinositol 3-kinase pathway, and on mitogen-activated protein kinase
      (MAPK), all three of which are activated by IGF-mediated signaling pathways and
      have important roles in cell survival. IGFBP-3 overexpression inhibited the
      phosphorylation of Akt and glycogen synthase kinase-3beta and the activity of
      MAPK. Furthermore, IGF-I rescued the NSCLC cells from serum depletion-induced
      apoptosis, and this rescue was blocked in Ad5CMV-BP-3-infected H1299 NSCLC cells.
      Transient transfection with activated Akt or constitutively active MAPK kinase-1,
      an upstream activator of MAPK, partially blocked IGFBP-3-induced apoptosis of
      NSCLC cells. These findings suggested that the growth-regulatory effect of IGFBP
      3 on NSCLC cells was attributable in part to the inhibition of the IGF-induced
      survival pathway. These data demonstrate the importance of IGFBP-3 in the
      regulation of NSCLC cell proliferation, clonogenicity, and tumor growth,
      suggesting that IGFBP-3 is a target for the treatment of lung cancer and that
      Ad5CMV-BP3 is a potential therapeutic agent.

PMID- 12068001
TI  - Transformation of mammary epithelial cells by 3-phosphoinositide-dependent
      protein kinase-1 (PDK1) is associated with the induction of protein kinase
      Calpha.
AB  - 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a mediator of multiple
      signaling pathways coupled to growth factor receptor activation in human cancers.
      To evaluate the role of PDK1 in mammary gland oncogenesis, COMMA-1D mouse mammary
      epithelial cells were retrovirally transduced with PDK1, and transformation was
      measured by anchorage-independent growth in soft agar. PDK1-expressing cells
      exhibited a high degree of transformation that was associated with the activation
      of Akt1 and an elevation of protein kinase Calpha (PKCalpha) expression. Cells
      overexpressing Akt1 did not exhibit anchorage-independent growth, whereas
      PKCalpha overexpression produced significant transformation, although to a lesser
      extent compared with PDK1. Coexpression of Akt1 and PKCalpha led to a more than
      additive effect on transformation activity. Isografts of either PDK1- or PKCalpha
      expressing cells but not Akt1-expressing cells in syngeneic mice led to formation
      of poorly differentiated mammary carcinomas. PDK1 was highly expressed in a
      majority of human breast cancer cell lines. These results suggest that activation
      of PDK1 can lead to mammary tumorigenesis, in part through PKCalpha, and that
      PDK1 expression may be an important target in human breast cancer.

PMID- 12068002
TI  - Ciliary neurotrophic factor (CNTF) in combination with its soluble receptor
      (CNTFRalpha) increases connexin43 expression and suppresses growth of C6 glioma
      cells.
AB  - The loss of gap junctional intercellular communication has been proposedas
      playing a major role in the process of carcinogenesis. Most neoplastic cells,
      including C6 gliomas, express less connexins and have fewer gap junctions,
      reduced gap junctional intercellular communication, and increased growth rates
      compared with their nonneoplastic counterparts. The purpose of this study was to
      determine whether ciliary neurotrophic factor (CNTF) can be used to increase
      endogenous connexin43 levels, increase intercellular coupling, and retard the
      growth rate of C6 glioma cells. C6 cells were grown in serum-reduced medium (1%
      serum) and exposed to the following agents: vehicle (PBS), CNTF (20 ng/ml), CNTF
      soluble receptor (CNTFRalpha; 200 ng/ml), or Complex (CNTF + CNTFRalpha). Reverse
      transcription-PCR analysis indicated that C6 cells express CNTF mRNA but not
      CNTFRalpha mRNA. When cells were exposed to the above agents, only Complex caused
      an up-regulation of connexin43 protein (based on immunocytochemical and
      immunoblot analysis). Furthermore, Complex increased gap junctional coupling in
      C6 cells as noted by the passage of the gap junction permeable dye calcein.
      Finally, it was demonstrated that Complex-treatment reduces the growth rate of C6
      cells compared with all of the other agents tested. Taken together, this study
      has demonstrated that CNTF in combination with its soluble receptor can increase
      connexin43 expression, increase gap junctional coupling, and reduce the in vitro
      proliferation of C6 glioma cells.

PMID- 12068003
TI  - The B16F10 cell receptor for a metastasis-promoting site on laminin-1 is a
      heparan sulfate/chondroitin sulfate-containing proteoglycan.
AB  - Exposure to AG73, a synthetic peptide (LQVQLSIR) from the COOH-terminal region of
      the laminin alpha1 chain, induces a malignant phenotype in B16F10 melanoma cells.
      Coinjection of this peptide with the cells results in an increase of lung tumors
      and also the formation of liver tumors in approximately 50% of the mice (W. H.
      Kim et al., Int. J. Cancer, 77: 632-639, 1998). Here we have characterized the
      cell surface receptor and its functional groups on B16F10 cells. Peptide affinity
      chromatography identified a cell surface protein eluting with 1 M NaCl, which ran
      in SDS gels as a broad band of M(r) approximately 150,000-200,000. Digestion with
      heparitinase and chondroitinase produced a core protein of lower molecular weight
      (M(r) approximately 90,000). Involvement of the glycosaminoglycan (GAG) side
      chains was demonstrated by inhibition of cell binding to the peptide by heparin,
      heparan sulfate, and chondroitin sulfate B, but not by chondroitin sulfates A or
      C, or hyaluronic acid. The IC(50) for heparin was the lowest, followed by heparan
      sulfate, then chondroitin sulfate B, suggesting that the overall sulfation of the
      GAG side chain is critical. This was confirmed by inhibition of attachment with
      chemically modified heparin and heparan sulfate, which also showed that N or O
      linkages were not important for function. Using sized heparin fragments to
      inhibit cell binding to the peptide demonstrated that 16-mer is the minimum
      length required. B16F10 cells form a network when grown on Matrigel, and this is
      prevented by addition of the AG73 peptide. The GAGs alone did not affect network
      formation, but heparin, heparan sulfate, and chondroitin sulfate B reversed the
      inhibitory effect of the peptide, whereas other GAGs were inactive. Furthermore,
      removal of cell surface GAGs inhibited cell attachment to the peptide. Cells
      treated with glycosidases and coinjected with the peptide formed liver tumors
      equal to the control group receiving no peptide, suggesting that the GAGs play an
      early role in peptide-mediated tumor metastasis. These data indicate that the
      B16F10 cell receptor for a laminin metastasis-promoting sequence is a heparan
      sulfate/chondroitin sulfate-containing proteoglycan, and these GAG side chains
      are functionally important in the cell-peptide interaction.

PMID- 12068004
TI  - Insulin increases the sensitivity of tumors to irradiation: involvement of an
      increase in tumor oxygenation mediated by a nitric oxide-dependent decrease of
      the tumor cells oxygen consumption.
AB  - The effects of insulin on tumor oxygenation, perfusion, oxygen consumption,and
      radiation sensitivity were studied on two different mouse tumor models (TLT, a
      liver tumor, and FSAII, a fibrosarcoma). Anesthetized mice were infused with
      insulin i.v. at a rate of 16 milliUnits/kg/min for 25 min. Local tumor
      oxygenation measurements were carried out using two independent techniques:
      electron paramagnetic resonance oximetry and a fiber-optic device (OxyLite). Two
      complementary techniques were also used to assess the blood flow inside the
      tumor: a laser Doppler system (OxyFlo) and contrast-enhanced magnetic resonance
      imaging. The oxygen consumption rate of tumor cells after in vivo insulin
      infusion was measured using high frequency electron paramagnetic resonance
      oximetry. To know if insulin was able to enhance radiation-induced tumor regrowth
      delay, tumor-bearing mice were treated with 16 Gy of 250 kV radiation dose after
      insulin infusion. We provide evidence that insulin increases the local pressure
      of oxygen of tumors (from 0-3 mm Hg to 8-11 mm Hg) as well as the tumor response
      to irradiation (increasing regrowth delay by a factor of 2.11). We found that the
      insulin-induced increase of tumor pressure of oxygen: (a) is not caused by an
      increase in the tumor blood flow, which is even decreased after insulin infusion;
      (b) is because of a decrease in the tumor cell oxygen consumption (in vivo
      insulin consumed oxygen three times slower than control cells); and (c) is
      inhibited by a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine
      methyl ester, when injected i.p. at 15 micromol/kg(-1), 1 h before insulin
      infusion. We demonstrate by immunoblotting that the NO pathway involves a
      phosphorylation of endothelial NO synthase and showed a concomitant increase in
      the cyclic GMP tumor level. These findings provide unique insights into
      biological processes in tumors, new possible management for treating cancer
      patients, and raise major questions about the role of insulin secretion (fasting
      status and diabetes) in the clinical response of tumors to radiation therapy.

PMID- 12068005
TI  - Transcription profile of cells infected with human T-cell leukemia virus type I
      compared with activated lymphocytes.
AB  - Human T-cell leukemia virus type I (HTLV-I) is the etiologic agent for adult T
      cell leukemia and the neurological disorder tropical spastic paraparesis/HTLV-I
      associated myelopathy. CD4+ T lymphocytes, the primary hosts for HTLV-I, undergo
      a series of changes that lead to T-cell activation, immortalization, and
      transformation. To gain insight into the genetic differences between activated
      and HTLV-I-infected lymphocytes, we performed Affymetrix GeneChip analysis of
      activated and HTLV-I-infected cells. Using the Hu6800 GeneChip, we identified
      approximately 763 genes that had differentially regulated expression in at least
      three of five HTLV-I cell lines. Classification of these genes into functional
      groups including cellular receptors, kinases, phosphatases, cytokines, signal
      proteins, and transcription factors provides insight into genes and pathways that
      are differentially regulated during HTLV-I transformation.

PMID- 12068006
TI  - Tetraspanin CD9 is a "proteolipid," and its interaction with alpha 3 integrin in
      microdomain is promoted by GM3 ganglioside, leading to inhibition of laminin-5
      dependent cell motility.
AB  - GM3 ganglioside inhibits tetraspanin CD9-facilitated cell motility in various
      cell lines (Ono, M., Handa, K., Sonnino, S., Withers, D. A., Nagai, H., and
      Hakomori, S. (2001) Biochemistry 40, 6414-6421). We now report the following: (i)
      CD9 has the novel feature of being soluble in chloroform/methanol, and
      classifiable as "proteolipid"; (ii) CD9 and alpha(3) integrin were concentrated
      together in the low-density glycolipid-enriched microdomain (GEM) of ldlD/CD9
      cells, and the alpha(3) expression ratio (value for cells grown under +Gal
      condition divided by the value for cells grown under -Gal condition) in GEM of
      ldlD/CD9 cells was higher than that in control ldlD/moc cells, suggesting that
      CD9 recruits alpha(3) in GEM under +Gal condition, whereby GM3 is present. (iii)
      Chemical levels of alpha(3) and CD9 in the total extract or membrane fractions
      from cells grown under +Gal versus -Gal condition were nearly identical, whereas
      alpha(3) expressed at the cell surface, probed by antibody binding in flow
      cytometry, was higher under -Gal than +Gal condition. These results suggest that
      GM3 synthesized under +Gal condition promotes interaction of alpha(3) with CD9,
      which restricts alpha(3) binding to its antibody. A concept of the alpha(3)/CD9
      interaction promoted by GM3 was further supported by (i) co-immunoprecipitation
      of CD9 and alpha(3) under +Gal but not -Gal condition, (ii) enhanced co
      immunoprecipitation of CD9 and alpha(3) when GM3 was added exogenously to cells
      under -Gal condition, and (iii) the co-localization images of CD9 with alpha(3)
      and of GM3 with CD9 in fluorescence laser scanning confocal microscopy. Based on
      the promotion of alpha(3)/CD9 interaction by GM3 and the status of laminin-5 as a
      true ligand for alpha(3), the laminin-5/alpha(3)-dependent motility of ldlD/CD9
      cells was found to be greatly enhanced under -Gal condition, but strongly
      inhibited under +Gal condition. Such a motility difference under +Gal versus -Gal
      condition was not observed for ldlD/moc cells. The inhibitory effect observed in
      ldlD/CD9 cells under +Gal condition was reversed upon addition of anti-alpha(3)
      antibody and is therefore based on interaction between alpha(3), CD9, and GM3 in
      GEM.

PMID- 12068007
TI  - Mutations in the helix 3 region of the androgen receptor abrogate ARA70 promotion
      of 17beta-estradiol-induced androgen receptor transactivation.
AB  - The influence of estrogen on the development of the male reproductive system may
      be interrupted in a subset of partial androgen insensitivity syndrome (PAIS)
      patients. PAIS describes a wide range of male undermasculinization resulting from
      mutations in the androgen receptor (AR) or steroid metabolism enzymes that
      perturb androgen-AR regulation of male sex organ development. In this study, we
      are interested in determining if PAIS-derived AR mutants that respond normally to
      androgen have altered responses to estrogen in the presence of ARA70, a
      coregulator previously shown to enhance 17beta-estradiol E2-induced AR
      transactivation. The wild-type AR (wtAR) and two PAIS AR mutants, AR(S703G) and
      AR(E709K), all bind to androgen and E2 and subsequently translocate to the
      nucleus. Whereas ARA70 functionally interacts with the wtAR and the PAIS AR
      mutants in response to androgen, E2 only promotes the functional interaction
      between ARA70 and the wtAR but not the PAIS AR mutants. ARA70 increases E2
      competitive binding to the wtAR in the presence of low level androgen and also
      retards E2 dissociation from the wtAR. ARA70 is present in both the cytoplasm and
      the nucleus of various mouse testicular cells during early embryogenesis day 16,
      at postpartum day 0 during estradiol synthesis and in the Leydig cells at
      postpartum day 49. ARA70 may be unable to modulate the PAIS AR mutants-E2
      binding, diminishing the effect of E2 via AR during male reproductive system
      development in patients with such mutations. Therefore, the presence of ARA70 in
      the testosterone and E2-producing Leydig cells may enhance the overall activity
      of AR during critical stages of male sex organ development.

PMID- 12068008
TI  - Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6.
      Role for cyclic AMP-responsive element-binding protein and activator protein-1.
AB  - Prostaglandin E(2) (PGE(2)) is an arachidonic acid metabolite mainly produced by
      activated monocytes/macrophages (Mo/Mphi) that display broad immunomodulatory
      activities. Several viruses capable of infecting Mo/Mphi modulate PGE(2)
      synthesis in a way that favors the infection processes and the spread of virions.
      In the present work, we studied the effect of human herpesvirus 6 (HHV-6)
      infection of Mo/Mphi on PGE(2) synthesis. Our results indicate that HHV-6 induces
      COX-2 gene expression and PGE(2) synthesis within a few hours of infection. We
      mapped the different promoter elements associated with COX-2 gene activation by
      HHV-6 to two cis-acting elements: a cyclic AMP-responsive element and an
      activator protein-1 element. HHV-6 immediate-early protein 2 was identified as a
      modulator of COX-2 gene expression in Mo/Mphi. Finally, addition of PGE(2) to HHV
      6-infected peripheral blood mononuclear cells cultures was found to increase
      significantly viral replication. Overall, these results further contribute to the
      immunomodulatory properties of HHV-6 and highlight a potential role for
      eicosanoids in the replication process of this virus.

PMID- 12068009
TI  - Passive immunization against beta-amyloid peptide protects central nervous system
      (CNS) neurons from increased vulnerability associated with an Alzheimer's disease
      causing mutation.
AB  - To characterize the effects of the familial Alzheimer's disease-causing Swedish
      mutations of amyloid precursor protein (SwAPP) on the vulnerability of central
      nervous system neurons, we induced epileptic seizures in transgenic mice
      expressing SwAPP. The transgene expression did not change the seizure threshold,
      but consistently more neurons degenerated in brains of SwAPP mice as compared
      with wild-type littermates. The degenerating neurons were stained both by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling and by
      Gallyas silver impregnation. A susceptible population of neurons accumulated
      intracellular Abeta and immunoreacted with antibodies against activated caspase
      3. To demonstrate that increased Abeta levels mediated the increased
      vulnerability, we infused antibodies against Abeta and found a significant
      reduction in neuronal loss that was paralleled by decreased brain levels of
      Abeta. Because the SwAPP mice exhibited no amyloid plaques at the age of these
      experiments, transgenic overproduction of Abeta in brain rendered neurons
      susceptible to damage much earlier than the onset of amyloid plaque formation.
      Our data underscore the possibility that Abeta is toxic, that it increases the
      vulnerability of neurons to excitotoxic events produced by seizures, and that
      lowering Abeta by passive immunization can protect neurons from Abeta-related
      toxicity.

PMID- 12068010
TI  - Genetically altered mice with different sialyltransferase deficiencies show
      tissue-specific alterations in sialylation and sialic acid 9-O-acetylation.
AB  - Glycan chains on glycoconjugates traversing the Golgi apparatus are often
      terminated by sialic acid residues, which can also be 9-O-acetylated. This
      process involves competition between multiple Golgi enzymes. Expression levels of
      Golgi enzyme mRNAs do not always correlate with enzyme activity, which in turn
      cannot accurately predict glycan sequences found on cell surfaces. Here we
      examine the cell type-specific expression of terminal glycans in tissues of
      normal mice in comparison with animals deficient in ST6Gal-I (transfers alpha2-6
      linked sialic acid to Galbeta1-4GlcNAc) or ST3Gal-I (transfers alpha2-3-linked
      sialic acid to Galbeta1-3GalNAc). Tissues of ST6Gal-I null mice showed minimal
      binding of an alpha2-6-sialic acid-specific lectin, indicating that no other
      enzyme generates Siaalpha2-6Galbeta1-4GlcNAc and that Siaalpha2-6GalNAc (sialyl
      Tn) is rare in mice. However, exposed Galbeta1-4GlcNAc termini were only
      moderately increased, indicating that these can be partially capped by other
      enzymes. Indeed, Galalpha1-3Galbeta1-4GlcNAc and Fucalpha1-2Galbeta1-4GlcNAc
      termini were enhanced in some tissues. Many tissues of ST3Gal-I null animals
      showed increases in Galbeta1-3GalNAc termini, and some increases in poly-N
      acetyllactosamines. However, overall expression of alpha2-3-linked sialic acid
      was selectively reduced only in a few instances, indicating that other ST3Gal
      enzymes can generate this linkage in most tissues. Highly selective losses of 9-O
      acetylation of sialic acid residues were also observed, with ST6Gal-I deficiency
      causing loss on endothelium and ST3Gal-I deficiency giving a marked decrease on
      CD4(+) lymphocytes. These data demonstrate selective regulation of sialylation
      and 9-O-acetylation, point to cell types with potential physiological defects in
      null animals, and show in vivo evidence for competition between Golgi enzymes.

PMID- 12068011
TI  - Oxidant-induced vascular endothelial growth factor expression in human
      keratinocytes and cutaneous wound healing.
AB  - Neutrophils and macrophages, recruited to the wound site, release reactive oxygen
      species by respiratory burst. It is commonly understood that oxidants serve
      mainly to kill bacteria and prevent wound infection. We tested the hypothesis
      that oxidants generated at the wound site promote dermal wound repair. We
      observed that H(2)O(2) potently induces vascular endothelial growth factor (VEGF)
      expression in human keratinocytes. Deletion mutant studies with a VEGF promoter
      construct revealed that a GC-rich sequence from bp -194 to -50 of the VEGF
      promoter is responsible for the H(2)O(2) response. It was established that at
      microm concentrations oxidant induces VEGF expression and that oxidant-induced
      VEGF expression is independent of hypoxia-inducible factor (HIF)-1 and dependent
      on Sp1 activation. To test the effect of NADPH oxidase-generated reactive oxygen
      species on wound healing in vivo, Rac1 gene transfer was performed to dermal
      excisional wounds left to heal by secondary intention. Rac1 gene transfer
      accelerated wound contraction and closure. Rac1 overexpression was associated
      with higher VEGF expression both in vivo as well in human keratinocytes.
      Interestingly, Rac1 gene therapy was associated with a more well defined
      hyperproliferative epithelial region, higher cell density, enhanced deposition of
      connective tissue, and improved histological architecture. Overall, the
      histological data indicated that Rac1 might be an important stimulator of various
      aspects of the repair process, eventually enhancing the wound-healing process as
      a whole. Taken together, the results of this study indicate that wound healing is
      subject to redox control.

PMID- 12068012
TI  - The C-type lectin receptor Endo180 displays internalization and recycling
      properties distinct from other members of the mannose receptor family.
AB  - Endo180/urokinase plasminogen activator receptor-associated protein together with
      the mannose receptor, the phospholipase A(2) receptor, and DEC-205/MR6-gp200
      comprise the four members of the mannose receptor family. These receptors have a
      unique structural composition due to the presence of multiple C-type lectin-like
      domains within a single polypeptide backbone. In addition, they are all
      constitutively internalized from the plasma membrane via clathrin-mediated
      endocytosis and recycled back to the cell surface. Endo180 is a multifunctional
      receptor displaying Ca(2+)-dependent lectin activity, collagen binding, and
      association with the urokinase plasminogen activator receptor, and it has a
      proposed role in extracellular matrix degradation and remodeling. Within their
      short cytoplasmic domains, all four receptors contain both a conserved tyrosine
      based and dihydrophobic-based putative endocytosis motif. Unexpectedly, Endo180
      was found to be distinct within the family in that the tyrosine-based motif is
      not required for efficient delivery to and recycling from early endosomes. By
      contrast, receptor internalization is completely dependent on the dihydrophobic
      motif and modulated by a conserved upstream acidic residue. Furthermore, unlike
      the mannose receptor, Endo180 does not function as a phagocytic receptor in
      vitro. These findings demonstrate that despite an overall structural similarity,
      members of this receptor family employ distinct trafficking mechanisms that may
      reflect important differences in their physiological functions.

PMID- 12068013
TI  - Definition of the first mannosylation step in phosphatidylinositol mannoside
      synthesis. PimA is essential for growth of mycobacteria.
AB  - We examined the function of the pimA (Rv2610c) gene, located in the vicinity of
      the phosphatidylinositol synthase gene in the genomes of Mycobacterium
      tuberculosis and Mycobacterium smegmatis, which encodes a putative
      mannosyltransferase involved in the early steps of phosphatidylinositol mannoside
      synthesis. A cell-free assay was developed in which membranes from M. smegmatis
      overexpressing the pimA gene incorporate mannose from GDP-[(14)C]Man into di- and
      tri-acylated phosphatidylinositol mono-mannosides. Moreover, crude extracts from
      Escherichia coli producing a recombinant PimA protein synthesized diacylated
      phosphatidylinositol mono-mannoside from GDP-[(14)C]Man and bovine
      phosphatidylinositol. To determine whether PimA is an essential enzyme of
      mycobacteria, we constructed a pimA conditional mutant of M. smegmatis. The
      ability of this mutant to synthesize the PimA mannosyltransferase was dependent
      on the presence of a functional copy of the pimA gene carried on a temperature
      sensitive rescue plasmid. We demonstrate here that the pimA mutant is unable to
      grow at the higher temperature at which the rescue plasmid is lost. Thus, the
      synthesis of phosphatidylinositol mono-mannosides and derived higher
      phosphatidylinositol mannosides in M. smegmatis appears to be dependent on PimA
      and essential for growth. This work provides the first direct evidence of the
      essentiality of phosphatidylinositol mannosides for the growth of mycobacteria.

PMID- 12068014
TI  - MDM2 inhibits PCAF (p300/CREB-binding protein-associated factor)-mediated p53
      acetylation.
AB  - Our previous study shows that MDM2, a negative feedback regulator of the tumor
      suppressor p53, inhibits p300-mediated p53 acetylation. Because PCAF (p300/CREB
      binding protein-associated factor) also acetylates and activates p53 after DNA
      damage, in this study we have examined the effect of MDM2 on PCAF-mediated p53
      acetylation. We have found that MDM2 inhibited p53 acetylation by PCAF in vitro.
      In addition, when overexpressed, MDM2 inhibited PCAF-mediated p53 acetylation in
      cells. MDM2 interacted with PCAF both in vitro and in cells, as assessed using
      GST fusion protein interaction and immunoprecipitation assays, respectively.
      Consistent with the above results, MDM2 significantly repressed the activation of
      p53 transcriptional activity by PCAF without apparently affecting the level of
      p53. In addition, MDM2 co-resided with p53 at the p53-responsive mdm2 and
      p21(waf1/cip1) promoters, inhibiting expression of the endogenous p21(waf1/cip1).
      These results demonstrate that MDM2 can inhibit PCAF-mediated p53 acetylation and
      activation.

PMID- 12068015
TI  - Mechanism of apoptosis induced by a new topoisomerase inhibitor through the
      generation of hydrogen peroxide.
AB  - TAS-103, a new anticancer drug, induces DNA cleavage by inhibiting the activities
      of topoisomerases I and II. We investigated the mechanism of TAS-103-induced
      apoptosis in human cell lines. Pulsed field gel electrophoresis revealed that in
      the leukemia cell line HL-60 and the H(2)O(2)-resistant subclone, HP100, TAS-103
      induced DNA cleavage to form 1-2-Mb fragments at 1 h to a similar extent,
      indicating that the DNA cleavage was induced independently of H(2)O(2). TAS-103
      induced DNA ladder formation in HP100 cells was delayed compared with that seen
      at 4 h in HL-60 cells, suggesting the involvement of H(2)O(2)-mediated pathways
      in apoptosis. Flow cytometry revealed that H(2)O(2) formation preceded increases
      in mitochondrial membrane potential (DeltaPsim) and caspase-3 activation.
      Inhibitors of poly(ADP-ribose) polymerase (PARP) prevented both TAS-103-induced
      H(2)O(2) generation and DNA ladder formation. The levels of NAD(+), a PARP
      substrate, were significantly decreased in HL-60 cells after a 3-h incubation
      with TAS-103. The decreases in NAD(+) levels preceded both increases in DeltaPsim
      and DNA ladder formation. Inhibitors of NAD(P)H oxidase prevented TAS-103-induced
      apoptosis, suggesting that NAD(P)H oxidase is the primary enzyme mediating
      H(2)O(2) formation. Expression of the antiapoptotic protein, Bcl-2, in BJAB cells
      drastically inhibited TAS-103-induced apoptosis, confirming that H(2)O(2)
      generation occurs upstream of mitochondrial permeability transition. Therefore,
      these findings indicate that DNA cleavage by TAS-103 induces PARP hyperactivation
      and subsequent NAD(+) depletion, followed by the activation of NAD(P)H oxidase.
      This enzyme mediates O(2)(-)-derived H(2)O(2) generation, followed by the
      increase in DeltaPsim and subsequent caspase-3 activation, leading to apoptosis.

PMID- 12068016
TI  - Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme
      endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
AB  - Haemophilus influenzae NadR protein (hiNadR) has been shown to be a bifunctional
      enzyme possessing both NMN adenylytransferase (NMNAT; EC ) and
      ribosylnicotinamide kinase (RNK; EC ) activities. Its function is essential for
      the growth and survival of H. influenzae and thus may present a new highly
      specific anti-infectious drug target. We have solved the crystal structure of
      hiNadR complexed with NAD using the selenomethionine MAD phasing method. The
      structure reveals the presence of two distinct domains. The N-terminal domain
      that hosts the NMNAT activity is closely related to archaeal NMNAT, whereas the C
      terminal domain, which has been experimentally demonstrated to possess
      ribosylnicotinamide kinase activity, is structurally similar to yeast thymidylate
      kinase and several other P-loop-containing kinases. There appears to be no cross
      talk between the two active sites. The bound NAD at the active site of the NMNAT
      domain reveals several critical interactions between NAD and the protein. There
      is also a second non-active-site NAD molecule associated with the C-terminal RNK
      domain that adopts a highly folded conformation with the nicotinamide ring
      stacking over the adenine base. Whereas the RNK domain of the hiNadR structure
      presented here is the first structural characterization of a ribosylnicotinamide
      kinase from any organism, the NMNAT domain of hiNadR defines yet another member
      of the pyridine nucleotide adenylyltransferase family.

PMID- 12068017
TI  - X-ray structure and ligand binding study of a moth chemosensory protein.
AB  - Chemosensory proteins (CSPs) are believed to be involved in chemical
      communication and perception. Such proteins, of M(r) 13,000, have been isolated
      from several sensory organs of a wide range of insect species. Several CSPs have
      been identified in the antennae and proboscis of the moth Mamestra brassicae. One
      of them, CSPMbraA6, a 112-amino acid antennal protein, has been expressed in
      large quantities and is soluble in the Escherichia coli periplasm. X-ray
      structure determination has been performed in parallel with ligand binding assays
      using tryptophan fluorescence quenching. The protein has overall dimensions of 25
      x 30 x 32 A and exhibits a novel type of alpha-helical fold with six helices
      connected by alpha-alpha loops. A narrow channel extends within the protein
      hydrophobic core. Fluorescence quenching with brominated alkyl alcohols or fatty
      acids and modeling studies indicates that CSPMbraA6 is able to bind such
      compounds with C12-18 alkyl chains. These ubiquitous proteins might have the role
      of extracting hydrophobic linear compounds (pheromones, odors, or fatty acids)
      dispersed in the phospholipid membrane and transporting them to their receptor.

PMID- 12068018
TI  - Distinct sulfation requirements of selectins disclosed using cells that support
      rolling mediated by all three selectins under shear flow. L-selectin prefers
      carbohydrate 6-sulfation totyrosine sulfation, whereas p-selectin does not.
AB  - l- and P-selectin are known to require sulfation in their ligand molecules. We
      investigated the significance of carbohydrate 6-sulfation and tyrosine sulfation
      in selectin-mediated cell adhesion. COS-7 cells were genetically engineered to
      express P-selectin glycoprotein ligand-1 (PSGL-1) or its mutant in various
      combinations with 6-O-sulfotransferase (6-Sul-T) and/or alpha1-
      >3fucosyltransferase VII (Fuc-T VII). The cells transfected with PSGL-1, 6-Sul-T,
      and Fuc-T VII cDNAs supported rolling mediated by all three selectins and
      provided the best experimental system so far to estimate kinetic parameters in
      selectin-mediated cell adhesion for all three selectins using the identical
      rolling substrate and to compare the ligand specificity of each selectin. L
      selectin-mediated rolling was drastically impaired if the cells lacked
      carbohydrate 6-sulfation elaborated by 6-Sul-T, but not affected when PSGL-1 was
      replaced with a mutant lacking three tyrosine residues at its NH(2) terminus. L
      selectin-mediated adhesion was also hardly affected by mocarhagin treatment of
      the cells, which cleaved a short peptide containing sulfated tyrosine residues
      from PSGL-1. In contrast, P-selectin-mediated rolling was abolished when PSGL-1
      was either mutated or cleaved by mocarhagin at its NH(2) terminus, whereas the
      cells expressing PSGL-1 and Fuc-T VII but not 6-Sul-T showed only a modest
      decrease in P-selectin-mediated adhesion. These results indicate that L-selectin
      prefers carbohydrate 6-sulfation much more than tyrosine sulfation, whereas P
      selectin favors tyrosine sulfation in the PSGL-1 molecule far more than
      carbohydrate 6-sulfation. E-selectin-mediated adhesion was sulfation-independent
      requiring only Fuc-T VII, and thus the three members of the selectin family have
      distinct requirements for ligand sulfation.

PMID- 12068019
TI  - Chinese hamster ovary cell motility to fibronectin is modulated by the second
      extracellular loop of CD9. Identification of a putative fibronectin binding site.
AB  - CD9, a member of the tetraspanin family of proteins, is characterized by four
      transmembrane domains and two extracellular loops. Surface expression of CD9 on
      Chinese hamster ovary (CHO) cells dramatically enhances spreading and motility on
      fibronectin. To elucidate the mechanistic basis of CD9-fibronectin interaction,
      binding to fibronectin was investigated using purified and recombinant forms of
      CD9. The affinity of fibronectin for CD9 in enzyme-linked immunosorbent assay was
      81 +/- 25 nm. The binding of fibronectin to immobilized CD9 was enhanced by
      Ca(2+) ions. Protein binding and peptide competition studies demonstrated that
      peptide 6 derived from CD9 extracellular loop 2 (amino acids 168-192) contained
      part of the fibronectin-binding domain. Additionally, enhanced adhesion of CD9
      CHO-B2 cells to fibronectin was significantly reduced by peptide 6. CD9-CHO cells
      had a 5-fold increase in motility to fibronectin as compared with mock
      transfected controls, an effect that correlated with CD9 cell surface density.
      Truncation of CD9 extracellular loop 2 and peptide 6 caused inhibition of CD9-CHO
      cell motility to fibronectin. Deletion of CD9 extracellular loop 1 had no
      significant effect on CHO cell motility. These findings demonstrate a critical
      role for CD9 extracellular loop 2 in cell motility to fibronectin and clarify the
      mechanism by which CD9-fibronectin interaction modulates cell adhesion and
      motility.

PMID- 12068021
TI  - The influence of protein structure on the products emerging from succinimide
      hydrolysis.
AB  - Proteins are vulnerable to spontaneous, covalent modifications that may result in
      alterations to structure and function. Asparagines are particularly labile, able
      to undergo deamidation through the formation of a succinimide intermediate to
      produce either aspartate or isoaspartate residues. Although aspartates cannot
      undergo deamidation they can form a succinimide and result in the same products.
      Isoaspartyls are the principal product of succinimide hydrolysis, accounting for
      65-85% of the emerging residues. The variability in the ratio of products
      emerging from succinimide hydrolysis suggests the ability of protein structure to
      influence succinimide outcome. In the H15D histidine-containing protein (HPr),
      phosphorylation of the active site aspartate catalyzes the formation of a cyclic
      intermediate. Resolution of this species is exclusively to aspartate residues,
      suggestive of either a succinimide with restrained hydrolysis, or an isoimide,
      from which aspartyl residues are the only possible product. Deletion of the C
      terminal residue of this protein does not influence the ability for
      phosphorylation or ring formation, but it does allow for isoaspartyl formation,
      verifying a succinimide as the cyclic intermediate in H15D HPr. Isoaspartyl
      formation in H15D Delta85 is rationalized to occur as a consequence of
      elimination of steric restrictions imposed by the C terminus on the main-chain
      carbonyl of the succinimide, the required point of nucleophilic attack of a water
      molecule for isoaspartyl formation. This is the first reported demonstration of
      the influence of protein structure on the products emerging from succinimide
      hydrolysis.

PMID- 12068020
TI  - The thrombin epitope recognizing thrombomodulin is a highly cooperative hot spot
      in exosite I.
AB  - The functional epitope of thrombin recognizing thrombomodulin was mapped using
      Ala-scanning mutagenesis of 54 residues located around the active site, the Na(+)
      binding loop, the 186-loop, the autolysis loop, exosite I, and exosite II. The
      epitope for thrombomodulin binding is shaped as a hot spot in exosite I, centered
      around the buried ion quartet formed by Arg(67), Lys(70), Glu(77), and Glu(80),
      and capped by the hydrophobic residues Tyr(76) and Ile(82). The hot spot is a
      much smaller subset of the structural epitope for thrombomodulin binding recently
      documented by x-ray crystallography. Interestingly, the contribution of each
      residue of the epitope to the binding free energy shows no correlation with the
      change in its accessible surface area upon formation of the thrombin
      thrombomodulin complex. Furthermore, residues of the epitope are strongly coupled
      in the recognition of thrombomodulin, as seen for the interaction of human growth
      hormone and insulin with their receptors. Finally, the Ala substitution of two
      negatively charged residues in exosite II, Asp(100) and Asp(178), is found
      unexpectedly to significantly increase thrombomodulin binding.

PMID- 12068023
TI  - Anderson-Fabry disease: its place among other genetic causes of renal disease.

PMID- 12068024
TI  - Biochemical and molecular genetic basis of Fabry disease.

PMID- 12068025
TI  - Renal pathology in Fabry disease.

PMID- 12068026
TI  - Natural history and treatment of renal involvement in Fabry disease.

PMID- 12068027
TI  - End-stage renal disease in patients with Fabry disease.

PMID- 12068028
TI  - Cardiac involvement in Anderson-Fabry disease.

PMID- 12068029
TI  - Anderson-Fabry disease: extrarenal, neurologic manifestations.

PMID- 12068030
TI  - A new sulfur-containing amino-acid isolated from the hydrolytic products of
      protein(Mueller, J. H. (1923) J. Biol. Chem. 56, 157-169).

PMID- 12068031
TI  - Phosphorylation-dependent differences in the activation properties of distal and
      proximal dendritic Na+ channels in rat CA1 hippocampal neurons.
AB  - At distal dendritic locations, the threshold for action potential generation is
      higher and the amplitude of back-propagating spikes is decreased. To study
      whether these characteristics depend upon Na+ channels, their voltage-dependent
      properties at proximal and distal dendritic locations were compared in CA1
      hippocampal neurons. Distal Na+ channels activated at more hyperpolarized
      voltages than proximal (half-activation voltages were -20.4 +/- 2.4 mV vs. -12.0
      +/- 1.7 mV for distal and proximal patches, respectively, n = 16, P < 0.01),
      while inactivation curves were not significantly different. The resting membrane
      potential of distal regions also appeared to be slightly but consistently more
      hyperpolarized than their proximal counterpart. Staurosporine, a non-selective
      protein kinase inhibitor, shifted the activation curves for both proximal and
      distal Na+ channels to the left so that they overlapped and also caused the
      resting potentials to be comparable. Staurosporine affected neither the
      inactivation kinetics of Na+ currents nor the reversal potential for Na+. These
      results suggest that the difference in the voltage dependence of activation of
      distal and proximal Na+ channels can be attributed to a different phosphorylation
      state at the two locations.

PMID- 12068032
TI  - In vivo analysis of Kvbeta2 function in Xenopus embryonic myocytes.
AB  - Kv1 potassium channels consist of pore-forming alpha subunits as well as
      auxiliary beta subunits. In heterologous systems, Kv1alpha subunits suffice for
      induction of voltage-dependent potassium current (I(Kv)). Although Kv1 channels
      can be expressed without auxiliary subunits in heterologous systems, coexpression
      with Kvbeta subunits has dramatic effects on surface expression and kinetic
      properties. Much less is known about the functional roles of Kvbeta subunits in
      vivo, despite their presence in the majority of native Kv1 channel complexes. We
      used an antisense approach to probe the contribution of Kvbeta2 subunits to
      native Kv1 channel function in embryonic myocytes. We compared the effects of
      antisense Kvbeta2 treatment on the whole cell I(Kv) to those produced by
      overexpression of a dominant-negative Kv1alpha subunit. The reductions in the
      maximal potassium conductance produced by antisense Kvbeta2 treatment and
      elimination of Kv1alpha subunit function were not significantly different from
      each other. In addition, simultaneous elimination of Kv1alpha and Kvbeta2 subunit
      function resulted in no further reduction of the maximal conductance. The Kv
      channel complexes targeted by Kvbeta2 and/or Kv1alpha subunit elimination
      contributed to action potential repolarization because elimination of either or
      both subunits led to increases in the duration of the action potential. As for
      potassium conductance, the effects of elimination of both alpha and beta subunits
      on the duration of the action potential were not additive. Taken together, the
      results suggest that Kv1 potassium channel complexes in vivo have a strong
      requirement for both alpha and beta subunits.

PMID- 12068033
TI  - Rhythm generation in monkey motor cortex explored using pyramidal tract
      stimulation.
AB  - We investigated whether stimulation of the pyramidal tract (PT) could reset the
      phase of 15-30 Hz beta oscillations observed in the macaque motor cortex. We
      recorded local field potentials (LFPs) and multiple single-unit activity from two
      conscious macaque monkeys performing a precision grip task. EMG activity was also
      recorded from the second animal. Single PT stimuli were delivered during the hold
      period of the task, when oscillations in the LFP were most prominent. Stimulus
      triggered averaging of the LFP showed a phase-locked oscillatory response to PT
      stimulation. Frequency domain analysis revealed two components within the
      response: a 15-30 Hz component, which represented resetting of on-going beta
      rhythms, and a lower frequency 10 Hz response. Only the higher frequency could be
      observed in the EMG activity, at stronger stimulus intensities than were required
      for resetting the cortical rhythm. Stimulation of the PT during movement elicited
      a greatly reduced oscillatory response. Analysis of single-unit discharge
      confirmed that PT stimulation was capable of resetting periodic activity in motor
      cortex. The firing patterns of pyramidal tract neurones (PTNs) and unidentified
      neurones exhibited successive cycles of suppression and facilitation, time locked
      to the stimulus. We conclude that PTN activity directly influences the generation
      of the 15-30 Hz rhythm. These PTNs facilitate EMG activity in upper limb muscles,
      contributing to corticomuscular coherence at this same frequency. Since the
      earliest oscillatory effect observed following stimulation was a suppression of
      firing, we speculate that inhibitory feedback may be the key mechanism generating
      such oscillations in the motor cortex.

PMID- 12068034
TI  - Cocaine binds to a common site on open and inactivated human heart (Na(v)1.5)
      sodium channels.
AB  - The inhibition by cocaine of the human heart Na+ channel (Na(v)1.5)
      heterologously expressed in Xenopus oocytes was investigated. Cocaine produced
      little tonic block of the resting channels but induced a characteristic, use
      dependent inhibition during rapid, repetitive stimulation, suggesting that the
      drug preferentially binds to the open or inactivated states of the channel. To
      investigate further the state dependence, depolarizing pulses were used to
      inactivate the channels and promote cocaine binding. Cocaine produced a slow,
      concentration-dependent inhibition of inactivated channels, which had an apparent
      K(D) of 3.4 microM. Mutations of the interdomain III-IV linker that remove fast
      inactivation selectively abolished this high-affinity component of cocaine
      inhibition, which appeared to be linked to the fast inactivation of the channels.
      A rapid component of cocaine inhibition persisted in the inactivation-deficient
      mutant that was enhanced by depolarization and was sensitive to changes in the
      concentration of external Na+, properties that are consistent with a pore
      blocking mechanism. Cocaine induced a use-dependent inhibition of the non
      inactivating mutant and delayed the repriming at hyperpolarized voltages,
      indicating that the drug slowly dissociated when the channels were closed.
      Mutation of a conserved aromatic residue (Y1767) of the D4S6 segment weakened
      both the inactivation-dependent and the pore-blocking components of the cocaine
      inhibition. The data indicate that cocaine binds to a common site located within
      the internal vestibule and inhibits cardiac Na+ channels by blocking the pore and
      by stabilizing the channels in an inactivated state.

PMID- 12068035
TI  - Convergent and reciprocal modulation of a leak K+ current and I(h) by an
      inhalational anaesthetic and neurotransmitters in rat brainstem motoneurones.
AB  - Neurotransmitters and volatile anaesthetics have opposing effects on motoneuronal
      excitability which appear to reflect contrasting modulation of two types of
      subthreshold currents. Neurotransmitters increase motoneuronal excitability by
      inhibiting TWIK-related acid-sensitive K+ channels (TASK) and shifting activation
      of a hyperpolarization-activated cationic current (I(h)) to more depolarized
      potentials; on the other hand, anaesthetics decrease excitability by activating a
      TASK-like current and inducing a hyperpolarizing shift in I(h) activation. Here,
      we used whole-cell recording from motoneurones in brainstem slices to test if
      neurotransmitters (serotonin (5-HT) and noradrenaline (NA)) and an anaesthetic
      (halothane) indeed compete for modulation of the same ion channels - and we
      determined which prevails. When applied together under current clamp conditions,
      5-HT reversed anaesthetic-induced membrane hyperpolarization and increased
      motoneuronal excitability. Under voltage clamp conditions, 5-HT and NA overcame
      most, but not all, of the halothane-induced current. When I(h) was blocked with
      ZD 7288, the neurotransmitters completely inhibited the K+ current activated by
      halothane; the halothane-sensitive neurotransmitter current reversed at the
      equilibrium potential for potassium (E(K)) and displayed properties expected of
      acid-sensitive, open-rectifier TASK channels. To characterize modulation of I(h)
      in relative isolation, effects of 5-HT and halothane were examined in acidified
      bath solutions that blocked TASK channels. Under these conditions, 5-HT and
      halothane each caused their characteristic shift in voltage-dependent gating of
      I(h). When tested concurrently, however, halothane decreased the neurotransmitter
      induced depolarizing shift in I(h) activation. Thus, halothane and
      neurotransmitters converge on TASK and I(h) channels with opposite effects;
      transmitter action prevailed over anaesthetic effects on TASK channels, but not
      over effects on I(h). These data suggest that anaesthetic actions resulting from
      effects on either TASK or hyperpolarization-activated cyclic nucleotide-gated
      (HCN) channels in motoneurones, and perhaps at other CNS sites, can be modulated
      by prevailing neurotransmitter tone.

PMID- 12068036
TI  - Voltage- and cation-dependent inactivation of L-type Ca2+ channel currents in
      guinea-pig ventricular myocytes.
AB  - L-type Ca2+ channel currents in native ventricular myocytes inactivate according
      to voltage- and Ca2+-dependent processes. This study sought to examine the effect
      of beta-adrenergic stimulation on the contributions of voltage and Ca2+ to Ca2+
      current decay. Ventricular myocytes were enzymatically isolated from guinea-pig
      hearts. Inward whole-cell Cd2+-sensitive L-type Ca2+ channel currents were
      recorded with the patch clamp technique and comparison was made between inward
      currents carried by Ca2+ and either Ba2+, Sr2+ or Na+. In control conditions the
      decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at negative
      voltages while at positive voltages there was no difference. The relationship
      between voltage and inactivation for Ca2+ currents was bell-shaped, while that
      for Ba2+, Sr2+, and Na+ currents was sigmoid. Thus depolarisation progressively
      replaced Ca2+-dependent inactivation in the fast phase of decay of Ca2+ channel
      currents with rapid voltage-dependent inactivation. In the presence of
      isoproterenol (isoprenaline) the decay of Ca2+ currents was faster than Ba2+,
      Sr2+ or Na+ currents at all measured voltages (-40 to +30 mV). The relationship
      between voltage and inactivation for Ca2+, Ba2+ and Sr2+ currents was bell
      shaped, while that for Na+ currents was sigmoid with less inactivation than under
      control conditions. Therefore the fast phase of decay of Ca2+ channel currents
      was now almost entirely due to Ca2+. It is concluded that the relative
      contributions of Ca2+- and voltage-dependent mechanisms of inactivation of L-type
      Ca2+ channels in native cardiac myocytes are modulated by beta-adrenergic
      stimulation influencing the amount of rapid voltage-dependent inactivation.

PMID- 12068037
TI  - beta-Adrenergic stimulation modulates Ca2+- and voltage-dependent inactivation of
      L-type Ca2+ channel currents in guinea-pig ventricular myocytes.
AB  - The objective of this study was to examine the effect of beta-adrenergic
      stimulation upon voltage- and Ca2+-induced inactivation of native cardiac L-type
      Ca2+ channels. Whole-cell currents were recorded from guinea-pig isolated
      ventricular myocytes. Total and voltage-dependent inactivation was separated by
      replacing extracellular Ca2+ with Mg2+. L-type Ca2+ channel behaviour was
      monitored with outward Ca2+ channel currents. First, the voltage dependence of
      inactivation was studied at fixed times (50 and 1000 ms) after activation. This
      showed that under control conditions Ca2+ contributed little to inactivation. In
      isoproterenol (isoprenaline), voltage-dependent inactivation was markedly reduced
      and Ca2+ contributed largely to total inactivation. Second, the time dependence
      of inactivation was studied at a fixed voltage (+10 mV). In control conditions
      the fast phase of inactivation (tau(f) approximately 15 ms) was reduced to the
      same extent by ryanodine (tau(f) approximately 30 ms) and the absence of Ca2+
      (tau(f) approximately 30 ms) while the slow phase of inactivation (tau(s)
      approximately 70 ms) was reduced by ryanodine (tau(s) approximately 160 ms) and
      further reduced in the absence of Ca2+ (tau(s) approximately 300 ms). In
      isoproterenol, biphasic inactivation of Ca2+ currents (tau(f) approximately 4 ms,
      tau(s) approximately 60 ms) was replaced by a single slow (tau approximately 450
      ms) phase of inactivation in the absence of Ca2+. It is concluded that, under
      control conditions Ca2+ channel current decay is largely dominated by rapid
      voltage-dependent inactivation, while in isoproterenol this is replaced by Ca2+
      induced inactivation.

PMID- 12068038
TI  - Carrier-mediated uptake and release of taurine from Bergmann glia in rat
      cerebellar slices.
AB  - Taurine uptake is essential for the maintenance of millimolar intracellular
      concentrations of taurine, which is released during ischaemia and is thought to
      be neuroprotective. To determine whether Bergmann glia express functional
      transporters that can mediate both taurine uptake and efflux, whole-cell patch
      clamp recordings were obtained from these cells in rat cerebellar slices. Taurine
      induced inward currents can be pharmacologically separated into GABA(A) receptor
      and taurine transporter currents. In the presence of GABA receptor blockers,
      residual taurine currents averaged -28 pA at -70 mV and were strictly inwardly
      rectifying between -70 and +50 mV. These residual currents were also abolished by
      external Na+ removal and diminished by reduction of external Cl-, consistent with
      transport currents. Taurine transport currents were reduced by a taurine
      transporter inhibitor, guanidinoethyl sulphonate (GES). Other classical
      inhibitors reduced taurine transport currents with an order of potency
      (hypotaurine > beta-alanine > GES > GABA) similar to that reported for cloned rat
      taurine transporters. Following intracellular taurine perfusion during the
      recording, a progressively developing outward current could be observed at -50 mV
      but not at -70 mV. Intracellular perfusion of taurine also decreased taurine
      induced inward currents at both holding potentials. Outward currents induced by
      intracellular taurine increased in amplitude with depolarization, activated near 
      50 mV, and were affected by GES. For the first time, these results demonstrate
      that taurine activates both GABA(A) receptors and Na+/Cl--dependent taurine
      transporters in Bergmann glia in slices. In addition, our data show that taurine
      transporters can work in reverse and can probably mediate taurine efflux under
      ischaemic conditions.

PMID- 12068039
TI  - Ionic currents in isolated and in situ squid Schwann cells.
AB  - Ionic currents from Schwann cells isolated enzymatically from the giant axons of
      the squids Loligo forbesi, Loligo vulgaris and Loligo bleekeri were compared with
      those obtained in situ. Macroscopic and single channel ionic currents were
      recorded using whole-cell voltage and patch clamp. In the whole-cell
      configuration, depolarisation from negative holding potentials evoked two voltage
      dependent currents, an inward current and a delayed outward current. The outward
      current resembled an outwardly rectifying K+ current and was activated at -40 mV
      after a latent period of 5-20 ms following a step depolarisation. The current was
      reduced by externally applied nifedipine, Co2+ or quinine, was not blocked by
      addition of apamin or charibdotoxin and was insensitive to externally applied L
      glutamate or acetylcholine. The voltage-gated inward current was activated at -40
      mV and was identified as an L-type calcium current sensitive to externally
      applied nifedipine. Schwann cells were impaled in situ in split-open axons and
      voltage clamped using discontinuous single electrode voltage clamp. Voltage
      dependent outward currents were recorded that were kinetically identical to those
      seen in isolated cells and that had similar current-voltage relations. Single
      channel currents were recorded from excised inside-out patches. A single channel
      type was observed with a reversal potential close to the equilibrium potential
      for K+ (E(K)) and was therefore identified as a K+ channel. The channel
      conductance was 43.6 pS when both internal and external solutions contained 150
      mM K+. Activity was weakly dependent on membrane voltage but sensitive to the
      internal Ca2+ concentration. Activity was insensitive to externally or internally
      applied L-glutamate or acetylcholine. The results suggest that calcium channels
      and calcium-activated K+ channels play an important role in the generation of the
      squid Schwann cell membrane potential, which may be controlled by the resting
      intracellular Ca2+ level.

PMID- 12068040
TI  - Rho family GTP binding proteins are involved in the regulatory volume decrease
      process in NIH3T3 mouse fibroblasts.
AB  - The role of Rho GTPases in the regulatory volume decrease (RVD) process following
      osmotic cell swelling is controversial and has so far only been investigated for
      the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the
      RVD process in NIH3T3 mouse fibroblasts, using wild-type cells and three clones
      expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in
      an up to fourfold increase in the rate of RVD, measured by large-angle light
      scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in
      wild-type cells was unaffected by the Rho kinase inhibitor Y-27632 and the
      phosphatidyl-inositol 3 kinase (PI3K) inhibitor wortmannin. The maximal rates of
      swelling-activated K+ (86 Rb+ as tracer) and taurine ([3H]taurine as tracer)
      efflux after a 30 % reduction in extracellular osmolarity were increased about
      twofold in cells with maximal RhoAV14 expression compared to wild-type cells, but
      were unaffected by Y-27632. The volume set points for activation of release of
      both osmolytes appeared to be reduced by RhoAV14 expression. The maximal taurine
      efflux rate constant was potentiated by the tyrosine phosphatase inhibitor
      Na(3)VO(4), and inhibited by the tyrosine kinase inhibitor genistein. The
      magnitude of the swelling-activated Cl- current (I(Cl,swell) ) was higher in
      RhoAV14 than in wild-type cells after a 7.5 % reduction in extracellular
      osmolarity, but, in contrast to 86Rb+ and [3H]taurine efflux, similar in both
      strains after a 30 % reduction in extracellular osmolarity. I(Cl,swell) was
      inhibited by Y-27632 and strongly potentiated by the myosin light chain kinase
      inhibitors ML-7 and AV25. It is suggested that RhoA, although not the volume
      sensor per se, is an important upstream modulator shared by multiple swelling
      activated channels on which RhoA exerts its effects via divergent signalling
      pathways.

PMID- 12068041
TI  - Voltage-dependent inward currents of interstitial cells of Cajal from murine
      colon and small intestine.
AB  - Electrical slow waves in gastrointestinal (GI) muscles are generated by pacemaker
      cells, known as interstitial cells of Cajal (ICC). The pacemaker conductance is
      regulated by periodic release of Ca2+ from inositol 1,4,5-trisphosphate (IP(3))
      receptor-operated stores, but little is known about how slow waves are actively
      propagated. We investigated voltage-dependent Ca2+ currents in cultured ICC from
      the murine colon and small intestine. ICC, identified by kit
      immunohistochemistry, were spontaneously active under current clamp and generated
      transient inward (pacemaker) currents under voltage clamp. Depolarization
      activated inward currents due to entry of Ca2+. Nicardipine (1 microM) blocked
      only half of the voltage-dependent inward current. After nicardipine, there was a
      shift in the potential at which peak current was obtained (-15 mV), and negative
      shifts in the voltage dependence of activation and inactivation of the remaining
      voltage-dependent inward current. The current that was resistant to
      dihydropyridine (I(VDDR)) displayed kinetics, ion selectivity and pharmacology
      that differed from dihydropyridine-sensitive Ca2+ currents. I(VDDR) was increased
      by elevating extracellular Ca2+ from 2 to 10 mM, and this caused a +30 mV shift
      in reversal potential. I(VDDR) was blocked by Ni2+ (100 microM) or mebefradil (1
      microM) but was not affected by blockers of N-, P- or Q-type Ca2+ channels.
      Equimolar replacement of Ca2+ with Ba2+ reduced I(VDDR) without effects on
      inactivation kinetics. BayK8644 had significantly less effect on I(VDDR) than on
      I(VDIC). In summary, two components of inward Ca2+ current were resolved in ICC
      of murine small intestine and colon. Since slow waves persist in the presence of
      dihydropyridines, the dyhydropyridine-resistant component of inward current may
      contribute to slow wave propagation.

PMID- 12068042
TI  - Vesicle pool partitioning influences presynaptic diversity and weighting in rat
      hippocampal synapses.
AB  - Hippocampal synapses display a range of release probabilities. This is partially
      the result of scaling of release probability with the total number of releasable
      vesicles at each synapse. We have compared synaptic release and vesicle pool
      sizes across a large number of hippocampal synapses using FM 1-43 and confocal
      fluorescence microscopy. We found that the relationship between the number of
      recycling vesicles at a synapse and its release probability is dependent on
      firing frequency. During firing at 10 Hz, the release probability of each synapse
      is closely related to the number of recycling vesicles that it contains. In
      contrast, during firing at 1 Hz, different synapses turn over their recycling
      vesicle pools at different rates leading to an indirect relationship between
      recycling vesicle pool size and release probability. Hence two synapses may
      release vesicles at markedly different rates during low frequency firing, even if
      they contain similar numbers of vesicles. Both further kinetic analyses and
      manipulation of the number of vesicles in the readily releasable pool using
      phorbol ester treatment suggested that this imprecise scaling observed during
      firing at 1 Hz resulted from synapse-to-synapse differences in the proportion of
      recycling vesicles partitioned into the readily releasable pool. Hence
      differential partitioning between vesicle pools affects presynaptic weighting in
      a frequency-dependent manner. Since hippocampal single unit firing rates shift
      between 1 Hz and 10 Hz regimes with behavioural state, differential partitioning
      may be a mechanism for encoding information in hippocampal circuits.

PMID- 12068043
TI  - Photolysis of caged cyclic AMP in the ciliary cytoplasm of the newt olfactory
      receptor cell.
AB  - The effects of cyclic nucleotide monophosphate (cNMP) in the ciliary cytoplasm of
      the olfactory receptor cell were examined by using photolysis of caged cNMP
      loaded from the whole-cell patch clamp pipette. Illumination of the cilia induced
      an inward current at -50 mV. The current amplitude was voltage dependent and the
      polarity was reversed at +10 mV. The amplitude of the light-induced current was
      dependent on both light intensity and duration. The intensity-response relation
      was fitted well by the Hill equation with a coefficient (n(H)) of 4.99 +/- 2.66
      (mean +/- S.D., n = 19) and the duration-response relation with a coefficient of
      4.03 +/- 1.43 (n = 17). The activation time course of adenylyl cyclase was
      estimated by comparing the light-induced response with the odorant-induced
      response. Adenylyl cyclase was activated approximately 260 ms later from the
      onset of the odorant-stimulation. The light-induced current developed very
      sharply. This could be explained by the sequential openings of cAMP-gated and
      Ca2+-activated Cl- channels. At +100 mV, where Ca2+ influx is expected to be very
      small, the current rising phase became less steep. When the cells were stimulated
      by long steps of either odour or light, the odorant-induced current showed
      stronger decay than the light-induced response. This observation suggests that
      the molecular system regulating desensitization is situated upstream of cAMP
      production.

PMID- 12068044
TI  - Fast-to-slow transformation and nuclear import/export kinetics of the
      transcription factor NFATc1 during electrostimulation of rabbit muscle cells in
      culture.
AB  - Contractile activity imposed by chronic electrical stimulation of a primary
      skeletal muscle cell culture grown on microcarriers over several days led to an
      increase of slow myosin heavy chain I (MHCI) and a decrease of fast MHCII
      expression at mRNA and protein levels, indicating an ongoing fast-to-slow
      transformation. Only patterns with periods of continuous stimulation of > or = 5
      min in a 45 min cycle were capable of inducing a fibre type transformation, and
      this was independent of the applied stimulation frequency over the range 1-10 Hz.
      We have shown before that the calcineurin-NFATc1 signalling pathway is
      indispensable in mediating MHCI upregulation during fibre type transformation.
      Therefore, subcellular localization of NFATc1 was studied immunocytochemically.
      This revealed that only one stimulation train lasting for > or = 5 min was
      sufficient to induce nuclear import of this factor, which was about complete
      after 20 min of continuous stimulation. For both induction of NFATc1 import and
      MHCI mRNA upregulation, the minimum stimulation interval of > or = 5 min was
      sufficient and stimulation frequency was not crucial between 1 and 10 Hz.
      Repetition of stimulation cycles, with pauses (40 min) shorter than the time
      required for complete export of NFATc1, led to an accumulation of NFATc1 in the
      nuclei with each cycle and thus to an amplification of the transformation signal
      during extended periods of electrostimulation. The temporal behaviour of NFATc
      import/export appears to determine the effectiveness of various
      electrostimulation protocols in inducing fast-to-slow fibre transformation.

PMID- 12068045
TI  - Intermittent ATP release from nerve terminals elicits focal smooth muscle Ca2+
      transients in mouse vas deferens.
AB  - A confocal Ca2+ imaging technique has been used to detect ATP release from
      individual sympathetic varicosities on the same nerve terminal branch. Varicose
      nerve terminals and smooth muscle cells in mouse vas deferens were loaded with
      the Ca2+ indicator Oregon Green 488 BAPTA-1. Field (nerve) stimulation evoked
      discrete, focal increases in [Ca2+] in smooth muscle cells adjacent to identified
      varicosities. These focal increases in [Ca2+] have been termed 'neuroeffector
      Ca2+ transients' (NCTs). NCTs were abolished by alpha,beta-methylene ATP (1
      microM), but not by nifedipine (1 microM) or prazosin (100 nM), suggesting that
      NCTs are generated by Ca2+ influx through P2X receptors without a detectable
      contribution from L-type Ca2+ channels or alpha(1)-adrenoceptor-mediated
      pathways. Action potential-evoked ATP release was highly intermittent (mean
      probability 0.019 +/- 0.002; range 0.001-0.10) at 1 Hz stimulation, even though
      there was no failure of action potential propagation in the nerve terminals.
      Twenty-eight per cent of varicosities failed to release transmitter following
      more than 500 stimuli. Spontaneous ATP release was very infrequent (0.0014 Hz).
      No Ca2+ transient attributable to noradrenaline release was detected even in
      response to 5 Hz stimulation. There was evidence of local noradrenaline release
      as the alpha(2)-adrenoceptor antagonist yohimbine increased the probability of
      occurrence of NCTs by 55 +/- 21 % during trains of stimuli at 1 Hz. Frequency
      dependent facilitation preferentially occurred at low probability release sites.
      The monitoring of NCTs now allows transmitter release to be detected
      simultaneously from each functional varicosity on an identified nerve terminal
      branch on an impulse-to-impulse basis.

PMID- 12068046
TI  - Different regional effects of voluntary exercise on the mechanical and electrical
      properties of rat ventricular myocytes.
AB  - Short-term (6 weeks) voluntary wheel running exercise in young female rats that
      were in an active growth phase resulted in whole-heart hypertrophy and myocyte
      concentric hypertrophy, when compared to sedentary controls. The cross-sectional
      area of ventricular myocytes from trained rats was significantly greater than for
      those isolated from sedentary rats, with the greatest change in morphology seen
      in sub-endocardial cells. There was no statistically significant effect of
      training on cell shortening in the absence of external mechanical loading, in
      [Ca2+](i) transients, or in myofilament Ca2+ sensitivity (assessed during re
      lengthening following tetanic stimulation). Under the external mechanical load of
      carbon fibres, absolute force developed in myocytes from trained rats was
      significantly greater than in those from sedentary rats. This suggests that
      increased myocyte cross-sectional area is a major contractile adaptation to
      exercise in this model. Training did not alter the passive mechanical properties
      of myocytes or the relative distribution of titin isomers, which was exclusively
      of the short, N2B form. However, training did increase the steepness of the
      active tension-sarcomere length relationship, suggesting an exercise-induced
      modulation of the Frank-Starling mechanism. This effect would be expected to
      enhance cardiac contractility. Training lengthened the action potential duration
      of sub-epicardial myocytes, reducing the transmural gradient in action potential
      duration. This observation may be important in understanding the cellular causes
      of T-wave abnormalities found in the electrocardiograms of some athletes. Our
      study shows that voluntary exercise modulates the morphological, mechanical and
      electrical properties of cardiac myocytes, and that this modulation is dependent
      upon the regional origin of the myocytes.

PMID- 12068047
TI  - Enhancement of calcium signalling dynamics and stability by delayed modulation of
      the plasma-membrane calcium-ATPase in human T cells.
AB  - In addition to its homeostatic role of maintaining low resting levels of
      intracellular calcium ([Ca2+](i)), the plasma-membrane calcium-ATPase (PMCA) may
      actively contribute to the generation of complex Ca2+ signals. We have
      investigated the role of the PMCA in shaping Ca2+ signals in Jurkat human
      leukaemic T cells using single-cell voltage-clamp and calcium-imaging techniques.
      Crosslinking the T-cell receptor with the monoclonal antibody OKT3 induces a
      biphasic elevation in [Ca2+](i) consisting of a rapid overshoot to a level > 1
      microM, followed by a slow decay to a plateau of approximately 0.5 microM. A
      similar overshoot was triggered by a constant level of Ca2+ influx through
      calcium-release-activated Ca2+ (CRAC) channels in thapsigargin-treated cells, due
      to a delayed increase in the rate of Ca2+ clearance by the PMCA. Following a rise
      in [Ca2+](i), PMCA activity increased in two phases: a rapid increase followed by
      a further calcium-dependent increase of up to approximately fivefold over 10-60
      s, termed modulation. After the return of [Ca2+](i) to baseline levels, the PMCA
      recovered slowly from modulation (tau approximately 4 min), effectively retaining
      a 'memory' of the previous [Ca2+](i) elevation. Using a Michaelis-Menten model
      with appropriate corrections for cytoplasmic Ca2+ buffering, we found that
      modulation extended the dynamic range of PMCA activity by increasing both the
      maximal pump rate and Ca2+ sensitivity (reduction of K(M)). A simple flux model
      shows how pump modulation and its reversal produce the initial overshoot of the
      biphasic [Ca2+](i) response. The modulation of PMCA activity enhanced the
      stability of Ca2+ signalling by adjusting the efflux rate to match influx through
      CRAC channels, even at high [Ca2+](i) levels that saturate the transport sites
      and would otherwise render the cell defenceless against additional Ca2+ influx.
      At the same time, the delay in modulation enables small Ca2+ fluxes to
      transiently elevate [Ca2+](i), thus enhancing Ca2+ signalling dynamics.

PMID- 12068048
TI  - Group I metabotropic glutamate receptors (mGluRs) modulate visual responses in
      the superficial superior colliculus of the rat.
AB  - Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the
      superficial layers of the rat superior colliculus (SSC) and SSC afferents. The
      purpose of this study was to investigate the physiological effect of Group I
      mGluR activation on visual responses of SSC neurones using both in vivo and in
      vitro techniques. In the in vivo preparation, agonists and antagonists were
      applied by iontophoresis and single neurone activity was recorded extracellularly
      in anaesthetised rats. Application of the Group I agonist (S)-3,5
      dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual
      response. The effect of DHPG could be blocked by concurrent application of the
      Group I (mGluR1/mGluR5) antagonist (S)-4-carboxyphenylglycine (4CPG) or mGluR1
      antagonist (+)-2-methyl-4-carboxyphenylglycine (LY367385). Application of 4CPG
      alone resulted in a facilitation of the visual response and this effect was not
      changed when the visual stimulus contrast was varied. Response habituation was
      observed when visual stimuli were presented at 0.5 s intervals, but this was not
      affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of
      the optic tract resulted in a field EPSP recorded from the SSC whose duration was
      increased in the presence of the GABA antagonists picrotoxin and CGP55845.
      Application of DHPG (5-100 microM) reduced the field EPSP, and this effect could
      be reversed by the mGluR1 antagonist LY367385 (200 microM), but not by the mGluR5
      antagonist MPEP (5 microM). These data show that activation of mGluR1, but
      probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and
      that this could be via presynaptic inhibition of glutamate release from either
      retinal or, possibly, cortical afferents.

PMID- 12068049
TI  - Contractile properties of isolated muscle spindles of the frog.
AB  - Force and isotonic shortening velocities were studied (0.6-4.0 degrees C) in
      isolated single muscle spindles from the anterior tibialis muscle of Rana
      temporaria using techniques that enabled measurements both from the spindle as a
      whole and from marked segments of the preparation. The force-velocity
      relationship during tetanic stimulation exhibited the same biphasic shape as
      previously described for extrafusal muscle fibres. However, the maximum speed of
      shortening of the spindle fibres was merely 0.95 +/- 0.006 lengths s(-1) (mean +/
      S.E.M., n = 11), which is approximately half the value recorded in extrafusal
      fibres of the same muscle. The maximum tetanic force, 91 +/- 10 kN m(-2), n = 14,
      was likewise only approximately half that produced by extrafusal fibres. The
      force generated by the capsule segment was lower than that produced by the whole
      spindle resulting in elongation of the capsule region during a fixed-end tetanus.
      The intracellular calcium ion concentration reached during the plateau of the
      tetanus, 1.7 +/- 0.1 microM (n = 8), was substantially lower than the value
      attained in extrafusal fibres under equivalent conditions. In accordance, the
      spindle fibres did not become fully activated during supramaximal electrical
      stimulation as indicated by the finding that the tetanic force could be further
      increased by 16.6 +/- 0.04 % (n = 5) on addition of 0.5 mM caffeine. Inadequate
      activation may thus, to a certain extent, account for the relatively low force
      per cross-sectional area of the spindle fibres. The contractile properties of the
      intrafusal fibres should make the spindle organ suited to provide feedback
      control during eccentric (forced lengthening) and static (isometric) contractions
      and, with reduced effectiveness, during slow muscle shortening.

PMID- 12068051
TI  - Influence of hypernatraemia and urea excretion on the ability to excrete a
      maximally hypertonic urine in the rat.
AB  - Rats normally excrete 20-25 mmol of sodium (Na+) + potassium (K+) per kilogram
      per day. To minimize the need for a large water intake, they must excrete urine
      with a very high electrolyte concentration (tonicity). Our objective was to
      evaluate two potential factors that could influence the maximum urine tonicity,
      hypernatraemia and the rate of urea excretion. Balance studies were carried out
      in vasopressin-treated rats fed a low-electrolyte diet. In the first series, the
      drinking solution contained an equivalent sodium chloride (NaCl) load at 150 or
      600 mmol l(-1). In the second series, the maximum urine tonicity was evaluated in
      rats consuming 600 mmol l(-1) NaCl with an 8-fold range of urea excretion.
      Hypernatraemia (148 +/- 1 mmol l(-1)) developed in all rats that drank 600 mmol
      l(-1) saline. Although the rate of Na+ + K+ excretion was similar in both saline
      groups, the maximum urine total cation concentration was significantly higher in
      the hypernatraemic group (731 +/- 31 vs. 412 +/- 37 mmol l(-1)). Only when the
      rate of excretion of urea was very low, was there a further increase in the
      maximum urine total cation concentration (1099 +/- 118 mmol l(-1)). Thus
      hypernatraemia was the most important factor associated with a higher urine
      tonicity.

PMID- 12068050
TI  - Pacemaker shift in the gastric antrum of guinea-pigs produced by excitatory vagal
      stimulation involves intramuscular interstitial cells.
AB  - Intracellular recordings were made from isolated bundles of the circular muscle
      layer of guinea-pig gastric antrum and the responses produced by stimulating
      intrinsic nerve fibres were examined. After abolishing the effects of stimulating
      inhibitory nerve terminals with apamin and L-nitroarginine (NOLA), transmural
      nerve stimulation often evoked a small amplitude excitatory junction potential
      (EJP) and invariably evoked a regenerative potential. Neurally evoked
      regenerative potentials had similar properties to those evoked in the same bundle
      by direct stimulation. EJPs and neurally evoked regenerative potentials were
      abolished by hyoscine suggesting that both resulted from the release of
      acetylcholine and activation of muscarinic receptors. Neurally evoked
      regenerative potentials, but not EJPs, were abolished by membrane
      hyperpolarization, caffeine and chloride channel blockers. In the intact antrum,
      excitatory vagal nerve stimulation increased the frequency of slow waves.
      Simultaneous intracellular recordings of pacemaker potentials from myenteric
      interstitial cells (ICC(MY)) and slow waves showed that the onset of each
      pacemaker potential normally preceded the onset of each slow wave but vagal
      stimulation caused the onset of each slow wave to precede each pacemaker
      potential. Together the observations suggest that during vagal stimulation there
      is a change in the origin of pacemaker activity with slow waves being initiated
      by intramuscular interstitial cells (ICC(IM)) rather than by ICC(MY).

PMID- 12068052
TI  - Modulation of synchrony between single motor units during precision grip tasks in
      humans.
AB  - During precision grip, coherence between motor cortex and hand muscle EMG
      oscillatory activity in the 15-30 Hz range covaries with the compliance of the
      manipulated object. The current study investigated whether short-term synchrony
      and coherence between discharges of single motor units (SMUs) in the first dorsal
      interosseous (1DI) muscle were similarly modulated by object compliance during
      precision grip. Eight subjects used index finger and thumb to grip two levers
      that were under robotic control. Guided by visual feedback of the lever force
      levels, subjects held the levers against a steady force of 1.3 N for 8 s; they
      then linearly increased the force to 1.6 N over a 2 s period and held for a
      further 8 s before linearly decreasing the force back to the 1.3 N level over
      another 2 s period. Subjects performed the task at two different levels of
      compliance, each with identical grip force levels. Both surface EMG and SMU
      activity were recorded from the 1DI muscle. Short-term synchrony between the
      discharges of pairs of SMUs was assessed in the time domain by cross-correlation
      and in the frequency domain by coherence analysis. Coherence was seen in two
      frequency ranges: 6-12 Hz and 15-30 Hz. The compliance of the gripped object had
      a significant effect on both short-term synchronisation and coherence in the 15
      30 Hz range between SMUs; both were greater for the more compliant condition.
      There was no change in the 6-12 Hz coherence.

PMID- 12068053
TI  - Interaction of transcranial magnetic stimulation and electrical transmastoid
      stimulation in human subjects.
AB  - Transcranial magnetic stimulation activates corticospinal neurones directly and
      transsynaptically and hence, activates motoneurones and results in a response in
      the muscle. Transmastoid stimulation results in a similar muscle response through
      activation of axons in the spinal cord. This study was designed to determine
      whether the two stimuli activate the same descending axons. Responses to
      transcranial magnetic stimuli paired with electrical transmastoid stimuli were
      examined in biceps brachii in human subjects. Twelve interstimulus intervals
      (ISIs) from -6 ms (magnet before transmastoid) to 5 ms were investigated. When
      responses to the individual stimuli were set at 10-15 % of the maximal M-wave,
      responses to the paired stimuli were larger than expected at ISIs of -6 and -5 ms
      but were reduced in size at ISIs of -2 to 1 ms and at 3 to 5 ms. With individual
      responses of 3-5 % of maximal M-wave, facilitation still occurred at ISIs of -6
      and -5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The
      interaction of the response to transmastoid stimulation with the multiple
      descending volleys elicited by magnetic stimulation of the cortex is complex.
      However, depression of the response to the paired stimuli at short ISIs is
      consistent with an occlusive interaction in which an antidromic volley evoked by
      the transmastoid stimulus collides with and annihilates descending action
      potentials evoked by the transcranial magnetic stimulus. Thus, it is consistent
      with the two stimuli activating some of the same corticospinal axons.

PMID- 12068054
TI  - Reflex regulation during sustained and intermittent submaximal contractions in
      humans.
AB  - To investigate whether the intensity and duration of a sustained contraction
      influences reflex regulation, we compared sustained fatiguing contractions at 25
      % and 50 % of maximal voluntary contraction (MVC) force in the human abductor
      pollicis brevis (APB) muscle. Because the activation of motoneurones during
      fatigue may be reflexively controlled by the metabolic status of the muscle, we
      also compared reflex activities during sustained and intermittent (6 s
      contraction, 4 s rest) contractions at 25 % MVC for an identical duration. The
      short-latency Hoffmann(H) reflex and the long-latency reflex (LLR) were recorded
      during voluntary contractions, before, during and after the fatigue tests, with
      each response normalised to the compound muscle action potential (M-wave). The
      results showed that fatigue during sustained contractions was inversely related
      to the intensity, and hence the duration, of the effort. The MVC force and
      associated surface electromyogram (EMG) declined by 26.2 % and 35.2 %,
      respectively, after the sustained contraction at 50 % MVC, and by 34.2 % and 44.2
      % after the sustained contraction at 25 % MVC. Although the average EMG increased
      progressively with time during the two sustained fatiguing contractions, the
      amplitudes of the H and LLR reflexes decreased significantly. Combined with
      previous data (Duchateau & Hainaut, 1993), the results show that the effect on
      the H reflex is independent of the intensity of the sustained contraction,
      whereas the decline in the LLR is closely related to the duration of the
      contraction. Because there were no changes in the intermittent test at 25 % MVC,
      the results indicate that the net excitatory spinal and supraspinal reflex
      mediated input to the motoneurone pool is reduced. This decline in excitation to
      the motoneurones, however, can be temporarily compensated by an enhancement of
      the central drive.

PMID- 12068055
TI  - Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of
      moderate exercise in man.
AB  - This study investigated intramuscular triacylglycerol (IMTG) and glycogen
      utilisation, pyruvate dehydrogenase activation (PDHa) and acetyl group
      accumulation during prolonged moderate intensity exercise. Seven endurance
      trained men cycled for 240 min at 57 % maximal oxygen consumption (V(O2,max)) and
      duplicate muscle samples were obtained at rest and at 10, 120 and 240 min of
      exercise. We hypothesised that IMTG utilisation would be augmented during 2-4 h
      of exercise, while PDHa would be decreased secondary to reduced glycogen
      metabolism. IMTG was measured on both muscle samples at each time point and the
      coefficient of variation was 12.3 +/- 9.4 %. Whole body respiratory exchange
      ratio (RER) decreased from 0.89 +/- 0.01 at 30 min to 0.83 +/- 0.01 at 150 min
      and remained low throughout exercise. Plasma glycerol and free fatty acids (FFAs)
      had increased compared with rest at 90 min and progressively increased until
      exercise cessation. Although plasma glucose tended to decrease with exercise,
      this was not significant. IMTG was reduced at 120 min compared with rest (0 min,
      15.6 +/- 0.8 mmol kg(-1) d.m.; 120 min, 12.8 +/- 0.7 mmol kg(-1) d.m.) but no
      further reduction in IMTG was observed at 240 min. Muscle glycogen was 468 +/- 49
      mmol kg(-1) d.m. at rest and decreased at 120 min and again at 240 min (217 +/-
      48 and 144 + 47 mmol kg(-1) d.m.). PDHa increased above rest at 10 and 120 min,
      but decreased at 240 min, which coincided with reduced whole body carbohydrate
      oxidation. Muscle pyruvate and ATP were unchanged with exercise. Acetyl CoA
      increased at 10 min and remained elevated throughout exercise. Acetylcarnitine
      increased at exercise onset but returned to resting values by 240 min. Contrary
      to our first hypothesis, significant utilisation of IMTG occurred during the
      first 2 h of moderate exercise but not during hours 2-4. The reduced utilisation
      of intramuscular fuels during the last 120 min was offset by greater FFA delivery
      and oxidation. Consistent with the second hypothesis, PDHa decreased late in
      moderate exercise and closely matched the estimates of lower carbohydrate flux.
      Although the factor underlying the PDHa decrease was not apparent, reduced
      pyruvate provision secondary to diminished glycolytic flux is the most likely
      mechanism.

PMID- 12068056
TI  - Role of 5'AMP-activated protein kinase in glycogen synthase activity and glucose
      utilization: insights from patients with McArdle's disease.
AB  - It has been suggested that 5'AMP-activated protein kinase (AMPK) is involved in
      the regulation of glucose and glycogen metabolism in skeletal muscle. We used
      patients with chronic high muscle glycogen stores and deficient glycogenolysis
      (McArdle's disease) as a model to address this issue. Six McArdle patients were
      compared with control subjects during exercise. Muscle alpha2AMPK activity
      increased in McArdle patients (from 1.3 +/- 0.2 to 1.9 +/- 0.2 pmol min(-1) mg(
      1), P = 0.05) but not in control subjects (from 1.0 +/- 0.1 to 1.3 +/- 0.3 pmol
      min(-1) mg(-1)). Exercise-induced phosphorylation of the in vivo AMPK substrate
      acetyl CoA carboxylase (ACCbeta; Ser(221)) was higher (P < 0.01) in McArdle
      patients than in control subjects (18 +/- 3 vs. 10 +/- 1 arbitrary units).
      Exercise-induced whole-body glucose utilization was also higher in McArdle
      patients than in control subjects (P < 0.05). No correlation between individual
      AMPK or ACCbeta values and glucose utilization was observed. Glycogen synthase
      (GS) activity was decreased in McArdle patients from 11 +/- 1.3 to 5 +/- 1.2 % (P
      < 0.05) and increased in control subjects from 19 +/- 1.6 to 23 +/- 2.3 % (P <
      0.05) in response to exercise. This was not associated with activity changes of
      GS kinase 3 or protein phosphatase 1, but the changes in GS activity could be due
      to changes in activity of AMPK or protein kinase A (PKA) as a negative
      correlation between either ACCbeta phosphorylation (Ser(221)) or plasma
      adrenaline and GS activity was observed. These findings suggest that GS activity
      is increased by glycogen breakdown and decreased by AMPK and possibly PKA
      activation and that the resultant GS activity depends on the relative strengths
      of the various stimuli. Furthermore, AMPK may be involved in the regulation of
      glucose utilization during exercise in humans, although the lack of correlation
      between individual AMPK activity or ACCbeta phosphorylation (Ser(221)) values and
      individual glucose utilization during exercise implies that AMPK may not be an
      essential regulator.

PMID- 12068057
TI  - Dynamic asymmetry of phosphocreatine concentration and O(2) uptake between the on
      and off-transients of moderate- and high-intensity exercise in humans.
AB  - The on- and off-transient (i.e. phase II) responses of pulmonary oxygen uptake
      (V(O(2))) to moderate-intensity exercise (i.e. below the lactate threshold,
      theta;(L)) in humans has been shown to conform to both mono-exponentiality and
      'on-off' symmetry, consistent with a system manifesting linear control dynamics.
      However above theta;(L) the V(O(2)) kinetics have been shown to be more complex:
      during high-intensity exercise neither mono-exponentiality nor 'on-off' symmetry
      have been shown to appropriately characterise the V(O(2)) response. Muscle
      [phosphocreatine] ([PCr]) responses to exercise, however, have been proposed to
      be dynamically linear with respect to work rate, and to demonstrate 'on-off'
      symmetry at all work intenisties. We were therefore interested in examining the
      kinetic characteristics of the V(O(2)) and [PCr] responses to moderate- and high
      intensity knee-extensor exercise in order to improve our understanding of the
      factors involved in the putative phosphate-linked control of muscle oxygen
      consumption. We estimated the dynamics of intramuscular [PCr] simultaneously with
      those of V(O(2)) in nine healthy males who performed repeated bouts of both
      moderate- and high-intensity square-wave, knee-extension exercise for 6 min,
      inside a whole-body magnetic resonance spectroscopy (MRS) system. A transmit
      receive surface coil placed under the right quadriceps muscle allowed estimation
      of intramuscular [PCr]; V(O(2)) was measured breath-by-breath using a custom
      designed turbine and a mass spectrometer system. For moderate exercise, the
      kinetics were well described by a simple mono-exponential function (following a
      short cardiodynamic phase for V(O(2))), with time constants (tau) averaging:
      tauV(O(2))(,on) 35 +/- 14 s (+/- S.D.), tau[PCr](on) 33 +/- 12 s,
      tauV(O(2))(,off) 50 +/- 13 s and tau[PCr](off) 51 +/- 13 s. The kinetics for both
      V(O(2)) and [PCr] were more complex for high-intensity exercise. The fundamental
      phase expressing average tau values of tauV(O(2))(,on) 39 +/- 4 s, tau[PCr](on)
      38 +/- 11 s, tauV(O(2))(,off) 51 +/- 6 s and tau[PCr](off) 47 +/- 11 s. An
      associated slow component was expressed in the on-transient only for both V(O(2))
      and [PCr], and averaged 15.3 +/- 5.4 and 13.9 +/- 9.1 % of the fundamental
      amplitudes for V(O(2)) and [PCr], respectively. In conclusion, the tau values of
      the fundamental component of [PCr] and V(O(2)) dynamics cohere to within 10 %,
      during both the on- and off-transients to a constant-load work rate of both
      moderate- and high-intensity exercise. On average, approximately 90 % of the
      magnitude of the V(O(2)) slow component during high-intensity exercise is
      reflected within the exercising muscle by its [PCr] response.

PMID- 12068058
TI  - Oxidative capacity interacts with oxygen delivery to determine maximal O(2)
      uptake in rat skeletal muscles in situ.
AB  - Based on proportional changes in V(O(2))(,max) with alterations in O(2) delivery,
      it is widely held that O(2) availability limits V(O(2))(,max). In contrast,
      reductions in V(O(2))(,max) are also seen when mitochondrial oxidative capacity
      is reduced. Taken collectively, these prior results are consistent with the
      notion that there is not a single-step limitation to V(O(2))(,max). We used a
      pump-perfused rat hindlimb model to test the hypothesis that combining moderate
      reductions in O(2) delivery and mitochondrial oxidative capacity would yield a
      greater reduction in V(O(2))(,max) than seen when performing each intervention
      independently, demonstrating an interaction between O(2) supply and mitochondrial
      oxidative capacity in determining V(O(2))(,max). Four groups of animals were
      studied: two in high O(2) delivery conditions (hindlimb O(2) delivery: 88 +/- 1
      micromol O(2) min(-1); mean +/- S.E.M.) and two in moderately reduced O(2)
      delivery conditions (66 +/- 2 micromol O(2) min(-1)). One group at each level of
      O(2) delivery was treated with 0.1 microM myxothiazol to reduce mitochondrial
      oxidative capacity via competitive inhibition of NADH cytochrome c reductase.
      V(O(2))(,max) in control animals (no myxothiazol) was 29 % lower in the
      moderately reduced O(2) delivery group (592 +/- 24 mmol O(2) min(-1) (100 g)(
      1)); P < 0.05) than in the high O(2) delivery group (833 +/- 63 micromol O(2)
      min(-1) (100 g)(-1)). Similarly, V(O(2))(,max) was reduced by 29 % (594 +/- 22
      micromol O(2) min(-1) (100 g)(-1)); P < 0.05) in myxothiazol-treated animals in
      high O(2) delivery conditions compared to control animals in high O(2) delivery
      conditions. When myxothiazol treatment was combined with moderately reduced O(2)
      delivery, V(O(2))(,max) was reduced by an additional 18 % (484 +/- 21 micromol
      O(2) min(-1) (100 g)(-1)); P < 0.05) compared to either intervention performed
      independently. These results show that O(2) supply and mitochondrial oxidative
      capacity interact to determine V(O(2))(,max).

PMID- 12068059
TI  - Hypoxia potentiates exocytosis and Ca2+ channels in PC12 cells via increased
      amyloid beta peptide formation and reactive oxygen species generation.
AB  - Exposure of PC12 cells to chronic hypoxia (CH; 10 % O(2), 24 h) augments
      catecholamine secretion via formation of a Cd2+-resistant Ca2+ influx pathway,
      and up-regulates native L-type Ca2+ channels. These effects are mimicked by
      exposure of cells to Alzheimer's disease-associated amyloid beta peptides
      (AbetaPs). Since pathological effects of AbetaPs have been associated with
      increased levels of reactive oxygen species (ROS), the involvement of ROS in
      hypoxia-mediated up-regulation of exocytosis and Ca2+ channel activity was
      examined. Both melatonin and ascorbic acid (two structurally unrelated
      antioxidants) fully blocked the enhancement of catecholamine secretion caused by
      CH (as determined amperometrically). Enhanced immunofluorescence, observed in
      chronically hypoxic cells using a primary monoclonal antibody raised against the
      N-terminus of AbetaP, was also suppressed by melatonin. Ascorbic acid, melatonin
      and ebselen (an additional antioxidant) also fully prevented augmentation of
      whole-cell Ca2+ currents caused by CH (as monitored using whole-cell patch-clamp
      recordings). Exposure of normoxic cells to H(2)O(2) (40 microM, 24 h), like
      hypoxia, caused Ca2+ channel up-regulation. Importantly, AbetaP formation
      appeared to be an absolute requirement for the effects of hypoxia, since the
      ability of CH to augment exocytosis and Ca2+ channel activity was blocked by two
      novel inhibitors of gamma secretase, an enzyme complex required for AbetaP
      formation. Our results indicate that the effects of hypoxia require ROS
      generation from AbetaPs, and suggest that elevated levels of ROS mediate hypoxic
      and AbetaP-mediated pathological remodelling of Ca2+ homeostasis.

PMID- 12068060
TI  - Responses of human sensory and motor axons to the release of ischaemia and to
      hyperpolarizing currents.
AB  - This study compared directly the post-ischaemic behaviour of sensory and motor
      axons in the human median nerve, focusing on the excitability changes produced by
      ischaemia and its release and by continuous polarizing DC. The decrease in
      threshold during ischaemia for 13 min was greater, the post-ischaemic increase in
      threshold was more rapid, and the return to the pre-ischaemic excitability took
      longer in sensory axons. However, a transient depolarizing threshold shift
      developed in sensory axons a few minutes after release of ischaemia. This pattern
      could not be reproduced by polarizing currents designed to mimic the probable
      pump-induced changes in membrane potential, even though the applied currents
      produced greater changes in threshold. Hyperpolarizing currents of equivalent
      intensity produced a greater increase in threshold for motor axons than sensory
      axons and, in studies of threshold electrotonus using graded hyperpolarizing DC,
      accommodation was greater in sensory than motor axons. The post-ischaemic changes
      in threshold were not uniform for axons of different threshold, whether sensory
      or motor, the threshold increase was usually less prominent for low-threshold
      axons. A transient post-ischaemic depolarization could be produced in motor axons
      with ischaemia of 20 min duration. Greater ischaemic and post-ischaemic changes
      in threshold for sensory axons could reflect greater dependence on the
      electrogenic Na+-K+ pump to maintain resting membrane potential and/or greater
      extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due
      to extracellular K+ accumulation would then be more likely to trigger a
      depolarizing shift in membrane potential, the degree of K+ accumulation and pump
      activity being dependent on the duration of ischaemia. In sensory axons the
      greater tendency to accommodate to hyperpolarizing stimuli presumably contributes
      to shaping their post-ischaemic behaviour but is probably insufficient to explain
      why their behaviour differs from that of motor axons.

PMID- 12068061
TI  - Salmon calcitonin - a potent inhibitor of food intake in states of impaired
      leptin signalling in laboratory rodents.
AB  - To compare the anorectic effectiveness of leptin and the amylin analogue salmon
      calcitonin (sCT), rodents were treated on 1 day with subcutaneous injections. In
      chow-fed C57Bl/6J mice, leptin and sCT reduced energy intake and acted
      additively. After C57Bl/6J mice had become leptin-resistant on being fed
      chocolate as a palatable high-caloric supplement to chow, their sCT-induced
      decrease in energy intake was more pronounced than in chow-fed mice with
      differential changes in the intake of chocolate (strong reduction) and chow
      (slight increase). Dose-response relationships for sCT-induced reductions in
      energy intake were analysed in chow-fed C57Bl/6J mice and two obese strains,
      ob/ob mice and melanocortin-4 receptor knockout (MC4-r-KO) mice, as well as in
      wild-type and fatty (fa/fa) rats. Compared to C57Bl/6J mice, reduction in food
      intake induced by sCT was attenuated in MC4-r-KO mice, and nearly absent in ob/ob
      mice, over the dose range investigated. Compared to C57Bl/6J mice, wild-type rats
      responded more sensitively to sCT and its efficiency was only slightly reduced in
      fatty (fa/fa) rats. Thus, while genetically induced failures of leptin signalling
      reduce the action of sCT, it effectively inhibits the intake of a palatable, high
      fat-high sugar diet even in states of diet-induced obesity with functional leptin
      resistance.

PMID- 12068062
TI  - Effect of exogenous and endogenous angiotensin II on intrarenal distribution of
      glomerular filtration rate in rats.
AB  - Different changes in glomerular filtration rates (GFR) in deep and superficial
      glomeruli have been suggested to influence renal NaCl excretion and concentrating
      ability. Angiotensin II (AngII) has been implicated in such changes, but the
      experimental evidence has been conflicting, probably because of the
      methodological limitation of just one 'snapshot' measurement of local GFR per
      kidney. We have therefore studied the effect of AngII and AT(1)-receptor blockade
      on glomerular filtration in outer, middle and inner cortex (OC, MC and IC,
      respectively) in pentobarbitone-anaesthetised rats using the aprotinin (Ap)
      method, providing control and experimental measurements in the same kidney.
      Glomerular filtration rate per gram cortical tissue was measured based on 'free'
      glomerular filtration of Ap followed by complete tubular uptake and a 20 min
      sojourn in the proximal tubular cells before breakdown and incipient return to
      the plasma.(125)I-labelled Ap was injected I.V. to determine control Ap
      clearance, followed after 13 min by injection of AngII or the A1 type AngII
      receptor blocker losartan and 2 min thereafter by (131)I-labelled Ap to determine
      clearance in the experimental period. Tracer activity in frequent blood samples
      and in tissue samples allowed calculation of GFR in the two periods. Mean GFR
      control values were: 1.13 ml min(-1) in whole kidney and 1.44, 1.27 and 0.76 ml
      min(-1) per gram cortical tissue in OC, MC and IC, respectively. The most
      sensitive and comprehensive measure of altered GFR distribution is the ratio
      between the relative filtration change in inner versus that in outer cortex, F =
      (IC(E)/IC(C))/(OC(E)/OC(C)), where subscripts E and C stand for experimental and
      control, respectively. F values greater than 1.00 directly indicate and quantify
      a relatively greater increase of filtration rate in inner than in outer cortex.
      We found in salt-replete rats that at practically unchanged total GFR,
      intravenous and intra-arterial infusion of AngII increased F to 1.07 and 1.04 (P
      < 0.05) whereas losartan reduced F to 0.99. After pretreatment with the inhibitor
      of nitric oxide production L-NAME, losartan increased total GFR by 8 % and F fell
      to 0.95 (P < 0.05). In salt-depleted rats losartan reduced F to 0.95 (P < 0.05)
      at unchanged total GFR. All IC/OC changes induced by losartan were significantly
      different from that obtained by AngII infusions. We conclude that deep nephrons
      have higher postglomerular AngII tone and also higher AngII sensitivity than
      superficial nephrons. The better preserved GFR in deep cortex during AngII action
      may contribute towards maintaining the renal concentrating ability by providing
      NaCl for reabsorption by the ascending limb of the loop of Henle.

PMID- 12068063
TI  - Alteration of amino acid metabolism in neuronal aggregate cultures exposed to
      hypoglycaemic conditions.
AB  - The neuronal effects of glucose deficiency on amino acid metabolism was studied
      on three-dimensional cultures of rat telencephalon neurones. Transient (6 h)
      exposure of differentiated cultures to low glucose (0.25 mm instead of 25 mm)
      caused irreversible damage, as judged by the marked decrease in the activities of
      two neurone-specific enzymes and lactate dehydrogenase, 1 week after the
      hypoglycemic insult. Quantification of amino acids and ammonia in the culture
      media supernatants indicated increased amino acid utilization and ammonia
      production during glucose-deficiency. Measurement of intracellular amino acids
      showed decreased levels of alanine, glutamine, glutamate and GABA, while
      aspartate was increased. Added lactate (11 mm) during glucose deficiency largely
      prevented the changes in amino acid metabolism and ammonia production, and
      attenuated irreversible damage. Higher media levels of glutamine (4 mm instead of
      0.25 mm) during glucose deprivation prevented the decrease of intracellular
      glutamate and GABA, while it further increased intracellular aspartate, ammonia
      production and neuronal damage. Both lactate and glutamine were readily oxidized
      in these neuronal cultures. The present results suggest that in neurones, glucose
      deficiency enhances amino acid deamination at the expense of transamination
      reactions. This results in increased ammonia production and neuronal damage.

PMID- 12068064
TI  - The C-terminal C1 cassette of the N -methyl-D-aspartate receptor 1 subunit
      contains a bi-partite nuclear localization sequence.
AB  - The N -methyl-D-aspartate receptor (NMDAR) is a multimeric transmembrane protein
      composed of at least two subunits. One subunit, NR1, is derived from a single
      gene and can be subdivided into three regions: the N-terminal extracellular
      domain, the transmembrane regions, and the C-terminal intracellular domain. The N
      terminal domain is responsible for Mg2+ metal ion binding and channel activity,
      while the transmembrane domains are important for ion channel formation. The
      intracellular C-terminal domain is involved in regulating receptor activity and
      subcellular localization. Our recent experiments indicated that the intracellular
      C-terminal domain, when expressed independently, localizes almost exclusively in
      the nucleus. An examination of the amino acid sequence reveals the presence of a
      putative nuclear localization sequence (NLS) in the C1 cassette of the NR1
      intracellular C-terminus. Using an expression vector designed to test whether a
      putative NLS sequence is a valid, functional NLS, we have demonstrated that a bi
      partite NLS does in fact exist within the NR1-1 C-terminus. Computer algorithms
      identified a putative helix-loop-helix motif that spanned the C0C1 cassettes of
      the C-terminus. These data suggest that the NR1 subunit may represent another
      member of a family of transmembrane proteins that undergo intramembrane
      proteolysis, releasing a cytosolic peptide that is actively translocated to the
      nucleus leading to alterations in gene regulation.

PMID- 12068065
TI  - Dibasic cleavage site is required for sorting to the regulated secretory pathway
      for both pro- and neuropeptide Y.
AB  - To investigate the signals governing routing of biologically active peptides to
      the regulated secretory pathway, we have expressed mutated and non-mutated
      proneuropeptide Y (ProNPY) in pituitary-derived AtT20 cells. The mutations were
      carried out on dibasic cleavage site and or ProNPY C-terminal sequence. Targeting
      to the regulated secretory pathway was studied using protein kinase A (8-BrcAMP),
      protein kinase C (phorbol myristate acetate) specific activators and protein
      synthesis inhibitor cycloheximide, and by pulse chase. The analysis of expressed
      peptides in cells and culture media indicated that: neuropeptide Y (NPY) and
      ProNPY were differently secreted, whilst NPY was exclusively secreted via
      regulatory pathway; ProNPY was secreted via regulated and constitutive-like
      secretory pathways. ProNPY secretion behaviour was not Proteolytic cleavage
      efficiency-dependent. The dibasic cleavage was essential for ProNPY and NPY cAMP
      dependent regulated secretion and may have function as a retention signal.

PMID- 12068066
TI  - PKC and Raf-1 inhibition-related apoptotic signalling in N2a cells.
AB  - In this study, a neuroblastoma N2a cell line was applied to investigate
      mechanisms of apoptosis induced either by selective inhibition of protein kinase
      C (PKC) by low amounts of staurosporine (STS(10) ) or by inhibition PI3-K after
      wortmannin (WM) treatment. We present evidence that, in the absence of serum in
      the medium, decreased phosphorylation of Raf-1 and BAD112, as well as Akt and
      BAD136, proteins and their translocation to mitochondria coincided with STS10 -
      or WM-induced apoptosis, respectively. Concomitantly, release of cytochrome c
      into the cytosol indicated a BCL-2-dependent mode of cell death after both
      treatments. Furthermore, in typical 'gain of function' experiments, cells with
      overexpression of permanently active Raf-1 or Akt transgenes displayed a
      significantly higher and independent resistance to either STS10 or WM. Thus, our
      results indicate that PKC/Raf-1/BAD112, as well as PI3-K/Akt/BAD136 signalling
      pathways, are both necessary for N2a cell survival and thus are unable to
      functionally substitute for each other as long as the cells do not receive
      additional signal(s) derived from serum. However, in the presence of serum,
      undefined trophic signal(s) can stimulate cross-talk between these two pathways
      at a level upstream from Raf-1 and Akt phosphorylation. In this case, only
      simultaneous inhibition of PKC and PI3-K is able to induce apoptosis.

PMID- 12068067
TI  - Potentiation of a sodium-calcium exchanger in the nuclear envelope by nuclear GM1
      ganglioside.
AB  - Calcium is recognized as an important intracellular messenger with a pivotal role
      in the regulation of many cytosolic and nuclear processes. Gangliosides of
      various types, especially GM1, are known to have a role in some aspects of Ca2+
      regulation, operating through a variety of mechanisms that are gradually coming
      to light. The present study provides evidence for a sodium-calcium exchanger in
      the nuclear envelope of NG108-15 neuroblastoma cells that is potently and
      specifically activated by GM1. Immunoblot analysis revealed an unusually tight
      association of GM1 with the exchanger in the nuclear envelope but not with that
      in the plasma membrane. Exchanger and associated GM1 were located in the inner
      membrane of the nuclear envelope, suggesting this system could function to
      transfer Ca2+ between nucleoplasm and the envelope lumen. The GM1-enhanced
      exchange was blocked by cholera toxin B subunit while C2-ceramide, a recently
      discovered inhibitor of the exchanger, blocked all transfer. Exchanger activity
      was significantly elevated in nuclei isolated from cells that were induced to
      differentiate by KCl + dibutyryl-cAMP, a treatment previously shown to promote up
      regulation of nuclear GM1 in conjunction with axonogenesis. Similar enhancement
      was achieved by addition of exogenous GM1 to nuclei from undifferentiated cells.
      These results suggest a prominent role for nuclear GM1 in regulation of nuclear
      Ca2+ homeostasis.

PMID- 12068068
TI  - Involvement of P2X7 receptors in the regulation of neurotransmitter release in
      the rat hippocampus.
AB  - Although originally cloned from rat brain, the P2X7 receptor has only recently
      been localized in neurones, and functional responses mediated by these neuronal
      P2X7 receptors (P2X7 R) are largely unknown. Here we studied the effect of P2X7 R
      activation on the release of neurotransmitters from superfused rat hippocampal
      slices. ATP (1-30 mm) and other ATP analogues elicited concentration-dependent [3
      H]GABA outflow, with the following rank order of potency: benzoylbenzoylATP
      (BzATP) > ATP > ADP. PPADS, the non-selective P2-receptor antagonist (3-30
      microm), Brilliant blue G (1-100 nm) the P2X7 -selective antagonist and Zn2+ (0.1
      30 microm) inhibited, whereas lack of Mg2+ potentiated the response by ATP. In
      situ hybridization revealed that P2X7 R mRNA is expressed in the neurones of the
      cell body layers in the hippocampus. P2X7 R immunoreactivity was found in
      excitatory synaptic terminals in CA1 and CA3 region targeting the dendrites of
      pyramidal cells and parvalbumin labelled structures. ATP (3-30 microm) and BzATP
      (0.6-6 microm) elicited concentration-dependent [14 C]glutamate efflux, and
      blockade of the kainate receptor-mediated transmission by CNQX (10-100 microm)
      and gadolinium (100 microm), decreased ATP evoked [3 H]GABA efflux. The Na+
      channel blocker TTX (1 microm), low temperature (12 degrees C), and the GABA
      uptake blocker nipecotic acid (1 mm) prevented ATP-induced [3 H]GABA efflux.
      Brilliant blue G and PPADS also reduced electrical field stimulation-induced [3
      H]GABA efflux. In conclusion, P2X7 Rs are localized to the excitatory terminals
      in the hippocampus, and their activation regulates the release of glutamate and
      GABA from themselves and from their target cells.

PMID- 12068069
TI  - The translocation of focal adhesion kinase in brain synaptosomes is regulated by
      phosphorylation and actin assembly.
AB  - Focal adhesion kinase (FAK) and the related proline-rich tyrosine kinase 2 (PYK2)
      are non-receptor protein tyrosine kinases that transduce extracellular signals
      through the activation of Src family kinases and are highly enriched in neurones.
      To further elucidate the regulation of FAK and PYK2 in nervous tissue, we
      investigated their distribution in brain subcellular fractions and analysed their
      translocation between membrane and cytosolic compartments. We have found that FAK
      and PYK2 are present in a small membrane-associated pool and a larger cytosolic
      pool in various neuronal compartments including nerve terminals. In intact nerve
      terminals, inhibition of Src kinases inhibited the membrane association of FAK,
      but not of PYK2, whereas tyrosine phosphatase inhibition sharply increased the
      membrane association of both FAK and PYK2. Disruption of the actin cytoskeleton
      was followed by a decrease in the membrane-associated pool of FAK, but not of
      PYK2. For both kinases, a significant correlation was found between
      autophosphorylation and membrane association. The data indicate that FAK and PYK2
      are present in nerve terminals and that the membrane association of FAK is
      regulated by both phosphorylation and actin assembly, whereas that of PKY2 is
      primarily dependent on its phosphorylation state.

PMID- 12068070
TI  - Expression and characterization of the Drosophila X11-like/Mint protein during
      neural development.
AB  - The X11-like (X11L) protein was originally isolated as a protein bound to the
      cytoplasmic domain of the beta-amyloid precursor protein (APP), which is
      associated with Alzheimer's disease. In mammals, X11L is believed to play an
      important role in the regulation of APP metabolism. Here we isolated and
      characterized the Drosophila X11L (dX11L) protein, also may be referred to this
      protein as Drosophila Mint (dMint), Lin 10 (dLin10) or X11 (dX11), is thought to
      be expressed in neuronal tissues from late embryonic through to the adult stages
      of the fly. The phosphotyrosine interaction domain of dX11L interacts with the
      cytoplasmic domain of the Drosophila amyloid precursor protein-like (APPL)
      similar to the way human X11L (hX11L) interacts with APP. Overexpression of dX11L
      on post-mitotic neurons had a lethal effect on flies and, when it was localized
      to the eye imaginal disc, disruption of compound eye morphology due to enhanced
      apoptosis of neuronal cells was observed. Overexpression of hX11L and the PDZ
      domain of dX11L resulted in identical eye phenotypes. The PDZ domain is highly
      conserved between Drosophila and human, and appears to be responsible for this
      phenotype. Our findings suggest that the X11L family may be involved with the
      regulation of apoptosis during neural cell development and that aberrant X11L
      function could be contribute in this way to the neuronal degeneration observed in
      Alzheimer's disease.

PMID- 12068071
TI  - Activation of the antioxidant response element in primary cortical neuronal
      cultures derived from transgenic reporter mice.
AB  - Many phase II protective genes contain a cis -acting enhancer region known as the
      antioxidant response element (ARE). Increased expression of these genes
      contributes to the protection of cells from oxidative stress. Transgenic reporter
      mice were created that carry in their genome the core ARE coupled to the human
      placental alkaline phosphatase (hPAP) reporter gene. Primary cortical cultures
      derived from these mice were treated with tBHQ resulting in a dose-dependent
      increase in hPAP activity. Histochemical staining for hPAP activity was observed
      in both glia and neurons from tBHQ-treated cultures. The tBHQ-mediated increase
      in hPAP was not affected by the antioxidant glutathione monoethyl ester (GSHEE),
      whereas the increase in hPAP following DEM treatment was completely blocked by
      GSHEE. Pre-treatment of cultures with the PI3-kinase inhibitor LY 294002
      demonstrated a dose-dependent decrease in tBHQ-induced hPAP activity. In
      addition, the tBHQ-mediated expression of ARE-driven genes in primary cortical
      cultures was blocked by LY 294002. Interestingly, basal expression of Nrf2 was
      also inhibited by LY 294002. We theorize that increased levels of genes
      controlled by the ARE are important for cellular protection against oxidative
      stress. These ARE-hPAP transgenic mice will be an important in vivo model for
      testing our hypothesis.

PMID- 12068072
TI  - Interleukin-4 and interleukin-10 modulate nuclear factor kappaB activity and
      nitric oxide synthase-2 expression in Theiler's virus-infected brain astrocytes.
AB  - In brain astrocytes, nuclear factor kappaB (NF-kappaB) is activated by stimuli
      that produce cellular stress causing the expression of genes involved in defence,
      including the inducible nitric oxide synthase (NOS-2). Theiler's murine
      encephalomyelitis virus (TMEV) induces a persistent CNS infection and chronic
      immune-mediated demyelination, similar to human multiple sclerosis. The cytokines
      interleukin (IL)-4 and IL-10 inhibit the expression of proinflammatory cytokines,
      counteracting the inflammatory process. Our study reports that infection of
      cultured astrocytes with TMEV resulted in a time-dependent phosphorylation of
      IkappaBalpha, degradation of IkappaBalpha and IkappaBbeta, activation of NF
      kappaB and expression of NOS-2. The proteasome inhibitor MG-132 blocked TMEV
      induced nitrite accumulation, NOS-2 mRNA expression and phospho-IkappaBalpha
      degradation, suggesting NF-kappaB-dependent NOS-2 expression. Pretreatment of
      astrocytes with IL-4 or IL-10 decreased p65 nuclear translocation, NF-kappaB
      binding activity and NOS-2 transcription. IL-4 and IL-10 caused an accumulation
      of IkappaBalpha in TMEV-infected astrocytes without affecting IkappaBbeta levels.
      The IkappaB kinase activity and the degradation rate of both IkappaBs were not
      modified by either cytokine, suggesting de novo synthesis of IkappaBalpha.
      Indeed, IL-4 or IL-10 up-regulated IkappaBalpha mRNA levels after TMEV infection.
      Therefore, the accumulation of IkappaBalpha might impair the translocation of the
      NF-kappaB to the nucleus, mediating the inhibition of NF-kappaB activity.
      Overall, these data suggest a novel mechanism of action of IL-4 and IL-10, which
      abrogates NOS-2 expression in viral-infected glial cells.

PMID- 12068073
TI  - Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in
      Schwann cells grown in elevated glucose.
AB  - In cultured Schwann cells, elevated glucose induces alterations in arachidonic
      acid metabolism that cause a decrease in the content of glycerophospholipid
      arachidonoyl-containing molecular species (ACMS). This could result from
      decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid
      release from phospholipids. Incorporation of radioactive 8,11,14-eicosatrienoic
      acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent
      with a decrease in delta5 desaturase activity. However, neither basal arachidonic
      acid release from prelabeled cells nor stimulated generation of arachidonic acid
      in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine
      phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered
      by varying the glucose concentrations, indicating that arachidonic acid turnover
      did not contribute to ACMS depletion. Free cytosolic NAD+ /NADH decreased,
      whereas NADP+ /NADPH remained unchanged for cells grown in elevated glucose,
      implying that decreased desaturase activity is a result of metabolic changes
      other than cofactor availability. Schwann cells in elevated glucose were
      susceptible to oxidative stress, as shown by increased malondialdehyde, depleted
      glutathione levels, and reduced cytosolic superoxide dismutase activity.
      Glutathione-altering compounds had no effect on ACMS levels, in contrast to N 
      acetylcysteine and alpha-lipoic acid, which partly corrected ACMS depletion in
      phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a
      high glucose level elicits oxidative stress and weakens antioxidant protection
      mechanisms which could decrease arachidonic acid biosynthesis and that this
      deficit can be partly corrected by treatment with exogenous antioxidants.

PMID- 12068074
TI  - Myelin-associated glycoprotein modulates expression and phosphorylation of
      neuronal cytoskeletal elements and their associated kinases.
AB  - Decreased phosphorylation of neurofilaments in mice lacking myelin-associated
      glycoprotein (MAG) was shown to be associated with decreased activities of
      extracellular-signal regulated kinases (ERK1/2) and cyclin-dependent kinase-5
      (cdk5). These in vivo changes could be caused directly by the absence of a MAG
      mediated signaling pathway or secondary to a general disruption of the Schwann
      cell-axon junction that prevents signaling by other molecules. Therefore, in
      vitro experimental paradigms of MAG interaction with neurons were used to
      determine if MAG directly influences expression and phosphorylation of
      cytoskeletal proteins and their associated kinases. COS-7 cells stably
      transfected with MAG or with empty vector were co-cultured with primary dorsal
      root ganglion (DRG) neurons. Total amounts of the middle molecular weight
      neurofilament subunit (NF-M), microtubule-associated protein 1B (MAP1B), MAP2,
      and tau were up-regulated significantly in DRG neurons in the presence of MAG.
      There was also increased expression of phosphorylated high molecular weight
      neurofilament subunit (NF-H), NF-M, and MAP1B. Additionally, in similar in vitro
      paradigms, total and phosphorylated NF-M were increased significantly in PC12
      neurons co-cultured with MAG-expressing COS cells or treated with a soluble MAG
      Fc-chimera. The increased expression of phosphorylated cytoskeletal proteins in
      the presence of MAG in vitro was associated with increased activities of ERK 1/2
      and cdk5. We propose that interaction of MAG with an axonal receptor(s) induces a
      signal transduction cascade that regulates expression of cytoskeletal proteins
      and their phosphorylation by these proline-directed protein kinases.

PMID- 12068075
TI  - Age-dependent decline of DNA repair activity for oxidative lesions in rat brain
      mitochondria.
AB  - Endogenous oxidative damage to brain mitochondrial DNA and mitochondrial
      dysfunction are contributing factors in aging and in the pathogenesis of a number
      of neurodegenerative diseases. In this study, we characterized the regulation of
      base-excision-repair (BER) activity, the predominant repair mechanism for
      oxidative DNA lesions, in brain mitochondria as the function of age.
      Mitochondrial protein extracts were prepared from rat cerebral cortices at the
      ages of embryonic day 17 (E17) or postnatal 1-, 2-, and 3-weeks, or 5- and 30
      months. The total BER activity and the activity of essential BER enzymes were
      examined in mitochondria using in vitro DNA repair assay employing specific
      repair substrates. Mitochondrial BER activity showed marked age-dependent
      declines in the brain. The levels of overall BER activity were highest at E17,
      gradually decreased thereafter, and reached to the lowest at the age of 30-month
      ( approximately 80% reduction). The decline of overall BER activity with age was
      attributed to the decreased expression of repair enzymes such as 8-OHdG
      glycosylase and DNA polymerase-gamma and, consequently, the reduced activity at
      the steps of lesion-base incision, DNA repair synthesis and DNA ligation in the
      BER pathway. These results strongly suggest that the decline in BER activity may
      be an important mechanism contributing to the age-dependent accumulation of
      oxidative DNA lesions in brain mitochondria.

PMID- 12068076
TI  - Microglial activation-mediated delayed and progressive degeneration of rat nigral
      dopaminergic neurons: relevance to Parkinson's disease.
AB  - The etiology of sporadic Parkinson's disease (PD) remains unknown. Increasing
      evidence has suggested a role for inflammation in the brain in the pathogenesis
      of PD. However, it has not been clearly demonstrated whether microglial
      activation, the most integral part of the brain inflammatory process, will result
      in a delayed and progressive degeneration of dopaminergic neurons in substantia
      nigra, a hallmark of PD. We report here that chronic infusion of an inflammagen
      lipopolysaccharide at 5 ng/h for 2 weeks into rat brain triggered a rapid
      activation of microglia that reached a plateau in 2 weeks, followed by a delayed
      and gradual loss of nigral dopaminergic neurons that began at between 4 and 6
      weeks and reached 70% by 10 weeks. Further investigation of the underlying
      mechanism of action of microglia-mediated neurotoxicity using rat mesencephalic
      neuron-glia cultures demonstrated that low concentrations of lipopolysaccharide
      (0.1-10 ng/mL)-induced microglial activation and production of neurotoxic factors
      preceded the progressive and selective degeneration of dopaminergic neurons.
      Among the factors produced by activated microglia, the NADPH oxidase-mediated
      release of superoxide appeared to be a predominant effector of neurodegeneration,
      consistent with the notion that dopaminergic neurons are particularly vulnerable
      to oxidative insults. This is the first report that microglial activation induced
      by chronic exposure to inflammagen was capable of inducing a delayed and
      selective degeneration of nigral dopaminergic neurons and that microglia
      originated free radicals play a pivotal role in dopaminergic neurotoxicity in
      this inflammation-mediated model of PD.

PMID- 12068077
TI  - Further characterization of the molecular interaction between PSD-95 and NMDA
      receptors: the effect of the NR1 splice variant and evidence for modulation of
      channel gating.
AB  - Coexpression of PSD-95(c-Myc) with NR1-1a/NR2A NMDA receptors in human embryonic
      kidney (HEK) 293 cells resulted in a decrease in efficacy for the glycine
      stimulation of [3 H]MK801 binding similar to that previously described for l
      glutamate. The inhibition constants (K (I) s) for the binding of l-glutamate and
      glycine to NR1-1a/NR2A determined by [3 H]CGP 39653 and [3 H]MDL 105 519
      displacement assays, respectively, were not significantly different between NR1
      1a/NR2A receptors coexpressed +/- PSD-95(c-Myc). The increased EC(50) for l
      glutamate enhancement of [3 H]MK801 binding was also found for NR1-2a/NR2A and
      NR1-4b/NRA receptors thus the altered EC(50) is not dependent on the N1, C1 or C2
      exon of the NR1 subunit. The NR1-4b but not the NR1-1a subunit was expressed
      efficiently at the cell surface in the absence of NR2 subunits. Total NR1-4b and
      NR1-4b/NR2A expression was enhanced by PSD-95(c-Myc) but whole cell enzyme-linked
      immunoadsorbent assays (ELISAs) showed that this increase was not due to
      increased expression at the cell surface. It is suggested that PSD-95(c-Myc) has
      a dual effect on NMDA receptors expressed in mammalian cells, a reduction in
      channel gating and an enhanced expression of NMDA receptor subunits containing C
      terminal E(T/S)XV PSD-95 binding motifs.

PMID- 12068078
TI  - Quantitative changes in mRNA expression of glutamate receptors in the rat
      peripheral and central vestibular systems following hypergravity.
AB  - In order to investigate the mechanisms responsible for adaptation to altered
      gravity, we assessed the changes in mRNA expression of glutamate receptors in
      vestibular ganglion cells, medial vestibular nucleus, spinal vestibular
      nucleus/lateral vestibular nucleus, cerebellar flocculus, and uvula/nodulus from
      rats exposed to hypergravity for 2 h to 1 week using real-time quantitative RT
      PCR methods. The mRNA expression of GluR2 and NR1 receptors in the uvula/nodulus
      and NR1 receptors in the medial vestibular nucleus increased in animals exposed
      to 2 h of hypergravity, and it decreased gradually to the control level. The mRNA
      expression of GluR2 receptors in vestibular ganglion cells decreased in animals
      exposed to 1 week of hypergravity. Neither the metabotropic glutamate receptor 1
      nor delta2 glutamate receptor in flocculus and uvula/nodulus was affected by a
      hypergravity load for 2 h to 1 week. It is suggested that the animals adapted to
      the hypergravity by enhancing the cerebellar inhibition of the vestibular nucleus
      neurons through activation of the NR1 and GluR2 receptors on the Purkinje cells
      in uvula/nodulus especially at the early phase following hypergravity. In the
      later phase following hypergravity, the animals adapted to the hypergravity by
      reducing the neurotransmission between the vestibular hair cells and the primary
      vestibular neurons via down-regulation of the postsynaptic GluR2 receptors in the
      vestibular periphery.

PMID- 12068079
TI  - Neurturin is a neuritogenic but not a survival factor for developing and adult
      central noradrenergic neurons.
AB  - Noradrenergic neurons of the locus coeruleus (LC) express the receptor tyrosine
      kinase c-ret, which binds ligands of the glial cell line-derived neurotrophic
      factor (GDNF) family. In the present study, we evaluated the function of
      neurturin (NTN), a GDNF family ligand whose function on LC neurons is unknown.
      Interestingly, we found that tyrosine hydroxylase (TH)-positive neurons in the LC
      express both GFRalpha1 and 2 receptors in a developmentally regulated fashion,
      suggesting a function for their preferred ligands: GDNF and NTN, respectively.
      Moreover, our results show that NTN mRNA expression is developmentally down
      regulated in the LC and peaks in the postnatal hippocampus and cerebral cortex,
      during the target innervation period. In order to examine the function of NTN, we
      next performed LC primary cultures, and found that neither GDNF nor NTN promoted
      the survival of TH-positive neurons. However, both factors efficiently induced
      neurite outgrowth in noradrenergic neurons (147% and 149% over controls,
      respectively). Similarly, grafting of fibroblast cell lines engineered to express
      high levels of NTN did not prevent the loss of LC noradrenergic neurons in a 6
      hydroxydopamine (6-OHDA) lesion model, but induced the sprouting of TH-positive
      cells. Thus our findings show that NTN does not promote the survival of LC
      noradrenergic neurons, but induces neurite outgrowth in developing noradrenergic
      neurons in vitro and in a model of neurodegeneration in vivo. These data,
      combined with data in the literature, suggest that GDNF family ligands are able
      to independently regulate neuronal survival and/or neuritogenesis.

PMID- 12068080
TI  - Glucose transport and utilization are altered in the brain of rats deficient in n
      3 polyunsaturated fatty acids.
AB  - Long-chain polyunsaturated (n-3) fatty acids have been reported to influence the
      efficiency of membrane receptors, transporters and enzymes. Because the brain is
      particularly rich in docosahexaenoic acid (DHA, 22:6 n-3), the present study
      addresses the question of whether the 22:6 n-3 fatty acid deficiency induces
      disorder in regulation of energy metabolism in the CNS. Three brain regions that
      share a high rate of energy metabolism were studied: fronto-parietal cortex,
      hippocampus and suprachiasmatic nucleus. The effect of the diet deficient in n-3
      fatty acids resulted in a 30-50% decrease in DHA in membrane phospholipids.
      Moreover, a 30% decrease in glucose uptake and a 20-40% decrease in cytochrome
      oxidase activity were observed in the three brain regions. The n-3 deficient diet
      also altered the immunoreactivity of glucose transporters, namely GLUT1 in
      endothelial cells and GLUT3 in neurones. In n-3 fatty acid deficient rats, GLUT1
      immunoreactivity readily detectable in microvessels became sparse, whereas the
      number of GLUT3 immunoreactive neurones was increased. However, western blot
      analysis showed no significant difference in GLUT1 and GLUT3 protein levels
      between rats deficient in n-3 fatty acids and control rats. The present results
      suggest that changes in energy metabolism induced by n-3 deficiency could result
      from functional alteration in glucose transporters.

PMID- 12068081
TI  - Identification of a novel SNAP25 interacting protein (SIP30).
AB  - Soluble N -ethylmaleimide-sensitive factor attachment protein receptors (SNAREs),
      including synaptosome-associated proteins of 25 kDa (SNAP25), syntaxins, and
      vesicle-associated membrane proteins (VAMP), are essential for regulated
      exocytosis of synaptic vesicles in neurotransmission. We identified a cDNA coding
      for a novel protein of 266 amino acids that we have named SIP30 (S NAP25
      interacting protein of 30 kDa). SIP30 is expressed abundantly in brain and
      slightly in testis and kidney. In brain, SIP30 is highly expressed in the
      inferior and superior colliculi, which contain important relay nuclei of the
      auditory and visual systems. GST-pull-down and immunoprecipitation assays showed
      direct binding of SIP30 to SNAP25. Although SIP30 does not directly interact with
      syntaxin based on pull-down assays, syntaxin does co-immunoprecipitate with SIP30
      suggesting that syntaxin is indirectly associated with SIP30, perhaps through
      SNAP25.

PMID- 12068082
TI  - Profound molecular changes following hippocampal slice preparation: loss of AMPA
      receptor subunits and uncoupled mRNA/protein expression.
AB  - The acute hippocampal slice preparation is a convenient, in vitro model widely
      used to study the biological basis of synaptic plasticity. Although slices may
      preserve their electrophysiological properties for several hours, profound
      molecular changes in response to the injury caused by the slicing procedure are
      likely to occur. To determine the magnitude and duration of these changes we
      examined the post-slicing expression kinetics of three classes of genes known to
      be implicated in long-term synaptic plasticity: glutamate AMPA receptors (GluR),
      transcription factors and neurotrophins. Slicing resulted in a striking loss of
      GluR1 and GluR3, but not of GluR2 proteins suggesting that rapid changes in the
      composition of major neurotransmitter receptors may occur. Slicing caused a
      significant induction of the transcription factors c-fos, zif268, CCAAT enhancer
      binding protein (C/EBP ) beta and delta mRNAs and of the neurotrophin brain
      derived neurothophic factor (BDNF ) mRNA. In contrast, there was no augmentation,
      and sometimes a decline, in the levels of the corresponding proteins. These data
      reveal that significant discrepancies exist between the slice preparation and the
      intact hippocampus in terms of the metabolism of molecular components known to be
      involved in synaptic plasticity.

PMID- 12068084
TI  - Agonists activate Gi1 alpha or Gi2 alpha fused to the human mu opioid receptor
      differently.
AB  - As preferential coupling of opioid receptor to various inhibitory Galpha subunits
      is still under debate, we have investigated the selectivity of the human mu
      opioid receptor fused to a pertussis toxin insensitive C351I Gi1 alpha or C352I
      Gi2 alpha in stably transfected HEK 293 cells. Overall agonist binding affinities
      were increased for both fusion constructs when compared to the wild type
      receptor. [35 S]GTPgammaS binding was performed on pertussis toxin treated cells
      to monitor coupling efficiency of the fusion constructs. Upon agonist addition
      hMOR-C351I Gi1 a exhibited an activation profile similar to the non-fused
      receptor while hMOR-C352I Gi2 alpha was poorly activated. Interestingly no
      correlation could be drawn between agonist binding affinity and efficacy. Upon
      agonist addition, forskolin-stimulated cAMP production, as measured using a
      reporter gene assay, was inhibited by signals transduced via the fused Gi1 alpha
      and Gi2 alpha mainly. In contrast both fusion constructs were able to initiate
      ERK-MAPK phosphorylation via coupling to endogenous G proteins only. In
      conclusion our data indicate that hMOR couples more efficiently to Gi1 alpha than
      Gi2 alpha and that the coupling efficacy is clearly agonist-dependent.

PMID- 12068083
TI  - Interferon-beta activates multiple signaling cascades in primary human microglia.
AB  - Microglia, the resident brain macrophages, are the principal cells involved in
      the regulation of inflammatory and antimicrobial responses in the CNS. Interferon
      beta (IFNbeta) is an antiviral cytokine induced by viral infection or following
      non-specific inflammatory challenges of the CNS. Because of the well-known anti
      inflammatory properties of IFNbeta, it is also used to treat multiple sclerosis,
      an inflammatory CNS disease. Despite the importance of IFNbeta signaling in CNS
      cells, little has been studied, particularly in microglia. In this report, we
      investigated the molecular mechanisms underlying IFNbeta-induced beta-chemokine
      expression in primary human fetal microglia. Multiple signaling cascades are
      activated in microglia by IFNbeta, including nuclear factor-kappaB (NF-kappaB),
      activator protein-1 (AP-1) and Jak/Stat. IFNbeta induced IkappaBalpha degradation
      and NF-kappaB (p65:p50) DNA binding. Inhibition of NF-kappaB by either adenoviral
      transduction of a super repressor IkappaBalpha, or an antioxidant inhibitor of NF
      kappaB reduced expression of the beta-chemokines, regulated upon activation,
      normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein
      (MIP)-1beta. IFNbeta also induced phosphorylation of extracellular signal
      regulated kinase (ERK) mitogen-activated protein kinase, and the MAP kinase
      kinase 1 (MEK1) inhibitor PD98059 dose-dependently inhibited beta-chemokine mRNA
      and protein expression. PD98059 did not inhibit NF-kappaB binding, demonstrating
      that ERK was not responsible for NF-kappaB activation. Two downstream targets of
      ERK were identified in microglia: AP-1 and Stat1. IFNbeta induced AP-1 nuclear
      binding activity in microglia and this was suppressed by PD98059. Additionally,
      IFNbeta induced Stat1 phosphorylation at both tyrosine 701 (Y701) and serine 727
      (S727) residues. S727 phosphorylation of Stat1, which is known to be required for
      maximal transcriptional activation, was inhibited by PD98059. Our results
      demonstrating multiple signaling cascades initiated by IFNbeta in primary human
      microglia are novel and have implications for inflammatory and infectious
      diseases of the CNS.

PMID- 12068085
TI  - Cationic interactions at the human dopamine transporter reveal binding
      conformations for dopamine distinguishable from those for the cocaine analog 2
      alpha-carbomethoxy-3 alpha-(4-fluorophenyl)tropane.
AB  - In membrane preparations, CFT, a phenyltropane cocaine analog, and dopamine (DA)
      interact with the recombinant human dopamine transporter (hDAT) in Na+ -free
      medium. Na+ markedly increased the transporter's affinity for CFT, but had little
      or no effect on DA potency for inhibiting CFT binding. Raising [Na+ ] from 20 to
      155 mm reduced Li+ -induced increase in DA K (i), but not CFT K (d). The presence
      of 155 mm Na+ enhanced the tolerance to low pH of CFT Kd but not DA Ki. Leucine
      substitution for tryptophan 84 (W84L) in transmembrane domain (TM) 1 or
      asparagine substitution for aspartate 313 (D313N) in TM 6 did not or only
      modestly enhance the affinity of Na+ -independent CFT binding, and retained the
      near normal ability of DA, Li+, K+, or H+ to inhibit this binding. However, the
      mutations significantly enhanced the Na+ stimulation of CFT binding as well as
      the Na+ antagonism against Li+ and H+ inhibition of CFT binding. In contrast, the
      mutations neither changed the Na+ -insensitive feature of DA Ki nor enhanced the
      Na+ protection of DA Ki against Li+ 's inhibitory effect, though they caused Na+
      protection of DA Ki against H+ 's inhibitory action. These results are consistent
      with the existence of binding conformations for DA that are distinguishable from
      those for CFT, and with a differential association of cation interactions with DA
      and CFT binding. The mutations likely alter Na+ -bound state(s) of hDAT,
      preferentially strengthening the positive allosteric coupling between Na+ and CFT
      binding, and reducing the impact of Li+ or H+ on the CFT binding.

PMID- 12068086
TI  - Specificity of resistance to oxidative stress.
AB  - Two clonal nerve-like cell lines derived from HT22 and PC12 have been selected
      for resistance to glutamate toxicity and amyloid toxicity, respectively. In the
      following experiments it was asked if these cell lines show cross-resistance
      toward amyloid beta peptide (Abeta) and glutamate as well as toward a variety of
      additional neurotoxins. Conversely, it was determined if inhibitors of oxytosis,
      a well-defined oxidative stress pathway, also protect cells from the neurotoxins.
      It is shown that both glutamate and amyloid resistant cells are cross resistant
      to most of the other toxins or toxic conditions, while inhibitors of oxytosis
      protect from glutathione and cystine depletion and H2O2 toxicity, but not from
      the toxic effects of nitric oxide, rotenone, arsenite or cisplatin. It is
      concluded that while there is a great deal of cross-resistance to neurotoxins,
      the components of the cell death pathway which has been defined for oxytosis are
      not used by many of the neurotoxins.

PMID- 12068087
TI  - Plant Physiology's Best Paper Award 2001.

PMID- 12068088
TI  - Arabidopsis functional genomics.

PMID- 12068090
TI  - Arabidopsis map-based cloning in the post-genome era.
AB  - Map-based cloning is an iterative approach that identifies the underlying genetic
      cause of a mutant phenotype. The major strength of this approach is the ability
      to tap into a nearly unlimited resource of natural and induced genetic variation
      without prior assumptions or knowledge of specific genes. One begins with an
      interesting mutant and allows plant biology to reveal what gene or genes are
      involved. Three major advances in the past 2 years have made map-based cloning in
      Arabidopsis fairly routine: sequencing of the Arabidopsis genome, the
      availability of more than 50,000 markers in the Cereon Arabidopsis Polymorphism
      Collection, and improvements in the methods used for detecting DNA polymorphisms.
      Here, we describe the Cereon Collection and show how it can be used in a generic
      approach to mutation mapping in Arabidopsis. We present the map-based cloning of
      the VTC2 gene as a specific example of this approach.

PMID- 12068091
TI  - Using cauliflower to find conserved non-coding regions in Arabidopsis.

PMID- 12068092
TI  - The cell wall-associated kinase (WAK) and WAK-like kinase gene family.

PMID- 12068093
TI  - Common components, networks, and pathways of cross-tolerance to stress. The
      central role of "redox" and abscisic acid-mediated controls.

PMID- 12068094
TI  - Calcium signaling through protein kinases. The Arabidopsis calcium-dependent
      protein kinase gene family.
AB  - In plants, numerous Ca(2+)-stimulated protein kinase activities occur through
      calcium-dependent protein kinases (CDPKs). These novel calcium sensors are likely
      to be crucial mediators of responses to diverse endogenous and environmental
      cues. However, the precise biological function(s) of most CDPKs remains elusive.
      The Arabidopsis genome is predicted to encode 34 different CDPKs. In this Update,
      we analyze the Arabidopsis CDPK gene family and review the expression,
      regulation, and possible functions of plant CDPKs. By combining emerging cellular
      and genomic technologies with genetic and biochemical approaches, the
      characterization of Arabidopsis CDPKs provides a valuable opportunity to
      understand the plant calcium-signaling network.

PMID- 12068097
TI  - Starch synthesis in Arabidopsis. Granule synthesis, composition, and structure.
AB  - The aim of this work was to characterize starch synthesis, composition, and
      granule structure in Arabidopsis leaves. First, the potential role of starch
      degrading enzymes during starch accumulation was investigated. To discover
      whether simultaneous synthesis and degradation of starch occurred during net
      accumulation, starch was labeled by supplying (14)CO(2) to intact,
      photosynthesizing plants. Release of this label from starch was monitored during
      a chase period in air, using different light intensities to vary the net rate of
      starch synthesis. No release of label was detected unless there was net
      degradation of starch during the chase. Similar experiments were performed on a
      mutant line (dbe1) that accumulates the soluble polysaccharide, phytoglycogen.
      Label was not released from phytoglycogen during the chase indicating that, even
      when in a soluble form, glucan is not appreciably degraded during accumulation.
      Second, the effect on starch composition of growth conditions and mutations
      causing starch accumulation was studied. An increase in starch content correlated
      with an increased amylose content of the starch and with an increase in the ratio
      of granule-bound starch synthase to soluble starch synthase activity. Third, the
      structural organization and morphology of Arabidopsis starch granules was
      studied. The starch granules were birefringent, indicating a radial organization
      of the polymers, and x-ray scatter analyses revealed that granules contained
      alternating crystalline and amorphous lamellae with a periodicity of 9 nm.
      Granules from the wild type and the high-starch mutant sex1 were flattened and
      discoid, whereas those of the high-starch mutant sex4 were larger and more
      rounded. These larger granules contained "growth rings" with a periodicity of 200
      to 300 nm. We conclude that leaf starch is synthesized without appreciable
      turnover and comprises similar polymers and contains similar levels of molecular
      organization to storage starches, making Arabidopsis an excellent model system
      for studying granule biosynthesis.

PMID- 12068095
TI  - Prediction of glycosylphosphatidylinositol-anchored proteins in Arabidopsis. A
      genomic analysis.
AB  - Glycosylphosphatidylinositol (GPI) anchoring of proteins provides a potential
      mechanism for targeting to the plant plasma membrane and cell wall. However,
      relatively few such proteins have been identified. Here, we develop a procedure
      for database analysis to identify GPI-anchored proteins (GAP) based on their
      possession of common features. In a comprehensive search of the annotated
      Arabidopsis genome, we identified 167 novel putative GAP in addition to the 43
      previously described candidates. Many of these 210 proteins show similarity to
      characterized cell surface proteins. The predicted GAP include homologs of beta
      1,3-glucanases (16), metallo- and aspartyl proteases (13),
      glycerophosphodiesterases (6), phytocyanins (25), multi-copper oxidases (2),
      extensins (6), plasma membrane receptors (19), and lipid-transfer-proteins (18).
      Classical arabinogalactan (AG) proteins (13), AG peptides (9), fasciclin-like
      proteins (20), COBRA and 10 homologs, and novel potential signaling peptides that
      we name GAPEPs (8) were also identified. A further 34 proteins of unknown
      function were predicted to be GPI anchored. A surprising finding was that over
      40% of the proteins identified here have probable AG glycosylation modules,
      suggesting that AG glycosylation of cell surface proteins is widespread. This
      analysis shows that GPI anchoring is likely to be a major modification in plants
      that is used to target a specific subset of proteins to the cell surface for
      extracellular matrix remodeling and signaling.

PMID- 12068098
TI  - NPSN11 is a cell plate-associated SNARE protein that interacts with the syntaxin
      KNOLLE.
AB  - SNAREs are important components of the vesicle trafficking machinery in
      eukaryotic cells. In plants, SNAREs have been found to play a variety of roles in
      the development and physiology of the whole organism. Here, we describe the
      identification and characterization of a novel plant-specific SNARE, NPSN11, a
      member of a closely related small gene family in Arabidopsis. NSPN11 is highly
      expressed in actively dividing cells. In a subcellular fractionation experiment,
      NSPN11 cofractionates with the cytokinesis-specific syntaxin, KNOLLE, which is
      required for the formation of the cell plate. By immunofluorescence microscopy,
      NSPN11 was localized to the cell plate in dividing cells. Consistent with the
      localization studies, NSPN11 was found to interact with KNOLLE. Our results
      suggest that NPSN11 is another component of the membrane trafficking and fusion
      machinery involved in cell plate formation.

PMID- 12068096
TI  - Two-component signal transduction pathways in Arabidopsis.
AB  - The two-component system, consisting of a histidine (His) protein kinase that
      senses a signal input and a response regulator that mediates the output, is an
      ancient and evolutionarily conserved signaling mechanism in prokaryotes and
      eukaryotes. The identification of 54 His protein kinases, His-containing
      phosphotransfer proteins, response regulators, and related proteins in
      Arabidopsis suggests an important role of two-component phosphorelay in plant
      signal transduction. Recent studies indicate that two-component elements are
      involved in plant hormone, stress, and light signaling. In this review, we
      present a genome analysis of the Arabidopsis two-component elements and summarize
      the major advances in our understanding of Arabidopsis two-component signaling.

PMID- 12068099
TI  - The branched-chain amino acid transaminase gene family in Arabidopsis encodes
      plastid and mitochondrial proteins.
AB  - Branched-chain amino acid transaminases (BCATs) play a crucial role in the
      metabolism of leucine, isoleucine, and valine. They catalyze the last step of the
      synthesis and/or the initial step of the degradation of this class of amino
      acids. In Arabidopsis, seven putative BCAT genes are identified by their
      similarity to their counterparts from other organisms. We have now cloned the
      respective cDNA sequences of six of these genes. The deduced amino acid sequences
      show between 47.5% and 84.1% identity to each other and about 30% to the
      homologous enzymes from yeast (Saccharomyces cerevisiae) and mammals. In
      addition, many amino acids in crucial positions as determined by crystallographic
      analyses of BCATs from Escherichia coli and human (Homo sapiens) are conserved in
      the AtBCATs. Complementation of a yeast Deltabat1/Deltabat2 double knockout
      strain revealed that five AtBCATs can function as BCATs in vivo. Transient
      expression of BCAT:green fluorescent protein fusion proteins in tobacco
      (Nicotiana tabacum) protoplasts shows that three isoenzymes are imported into
      chloroplasts (AtBCAT-2, -3, and -5), whereas a single enzyme is directed into
      mitochondria (AtBCAT-1).

PMID- 12068100
TI  - Signals involved in Arabidopsis resistance to Trichoplusia ni caterpillars
      induced by virulent and avirulent strains of the phytopathogen Pseudomonas
      syringae.
AB  - Plants have evolved different but interconnected strategies to defend themselves
      against herbivorous insects and microbial pathogens. We used an
      Arabidopsis/Pseudomonas syringae pathosystem to investigate the impact of
      pathogen-induced defense responses on cabbage looper (Trichoplusia ni) larval
      feeding. Arabidopsis mutants [npr1, pad4, eds5, and sid2(eds16)] or transgenic
      plants (nahG) that are more susceptible to microbial pathogens and are
      compromised in salicylic acid (SA)-dependent defense responses exhibited reduced
      levels of feeding by T. ni compared with wild-type plants. Consistent with these
      results, Arabidopsis mutants that are more resistant to microbial pathogens and
      have elevated levels of SA (cpr1 and cpr6) exhibited enhanced levels of T. ni
      feeding. These experiments suggested an inverse relationship between an active SA
      defense pathway and insect feeding. In contrast to these results, there was
      increased resistance to T. ni in wild-type Arabidopsis ecotype Columbia plants
      that were infected with P. syringae pv. maculicola strain ES4326 (Psm ES4326)
      expressing the avirulence genes avrRpt2 or avrB, which elicit a hypersensitive
      response, high levels of SA accumulation, and systemic acquired resistance to
      bacterial infection. Similar results were obtained with other ecotypes, including
      Landsberg erecta, Cape Verdi Islands, and Shakdara. When infected with Psm
      ES4326(avrRpt2) or Psm ES4326(avrB), nahG transgenic and npr1 mutant plants
      (which are more susceptible to virulent and avirulent P. syringae strains) failed
      to show the increased insect resistance exhibited by wild-type plants. It was
      surprising that wild-type plants, as well as nahG and npr1 plants, infected with
      Psm ES4326 not expressing avrRpt2 or avrB, which elicits disease, became more
      susceptible to T. ni. Our results suggest two potentially novel systemic
      signaling pathways: a systemic response elicited by HR that leads to enhanced T.
      ni resistance and overrides the SA-mediated increase in T. ni susceptibility, and
      a SA-independent systemic response induced by virulent pathogens that leads to
      enhanced susceptibility to T. ni.

PMID- 12068101
TI  - Regulation of CLV3 expression by two homeobox genes in Arabidopsis.
AB  - The ability of meristems to continuously produce new organs depends on the
      activity of their stem cell populations, which are located at the meristem tip.
      In Arabidopsis, the size of the stem cell domain is regulated by two antagonistic
      activities. The WUS (WUSCHEL) gene, encoding a homeodomain protein, promotes the
      formation and maintenance of stem cells. These stem cells express CLV3
      (CLAVATA3), and signaling of CLV3 through the CLV1/CLV2 receptor complex
      restricts WUS activity. Homeostasis of the stem cell population may be achieved
      through feedback regulation, whereby changes in stem cell number result in
      corresponding changes in CLV3 expression levels, and adjustment of WUS expression
      via the CLV signal transduction pathway. We have analyzed whether expression of
      CLV3 is controlled by the activity of WUS or another homeobox gene, STM (SHOOT
      MERISTEMLESS), which is required for stem cell maintenance. We found that
      expression of CLV3 depends on WUS function only in the embryonic shoot meristem.
      At later developmental stages, WUS promotes the level of CLV3 expression,
      together with STM. Within a meristem, competence to respond to WUS activity by
      expressing CLV3 is restricted to the meristem apex.

PMID- 12068102
TI  - Circadian rhythms confer a higher level of fitness to Arabidopsis plants.
AB  - Circadian rhythms have been demonstrated in organisms across the taxonomic
      spectrum. In view of their widespread occurrence, the adaptive significance of
      these rhythms is of interest. We have previously shown that constitutive
      expression of the CCA1 (CIRCADIAN CLOCK ASSOCIATED 1) gene in Arabidopsis plants
      (CCA1-ox) results in loss of circadian rhythmicity. Here, we demonstrate that
      these CCA1-ox plants retain the ability to respond to diurnal changes in light.
      Thus, transcript levels of several circadian-regulated genes, as well as CCA1
      itself and the closely related LHY, oscillate robustly if CCA1-ox plants are
      grown under diurnal conditions. However, in contrast with wild-type plants in
      which transcript levels change in anticipation of the dark/light transitions, the
      CCA1-ox plants have lost the ability to anticipate this daily change in their
      environment. We have used CCA1-ox lines to examine the effects of loss of
      circadian regulation on the fitness of an organism. CCA1-ox plants flowered
      later, especially under long-day conditions, and were less viable under very
      short-day conditions than their wild-type counterparts. In addition, we
      demonstrate that two other circadian rhythm mutants, LHY-ox and elf3, have low
      viability phenotypes. Our findings demonstrate the adaptive advantage of
      circadian rhythms in Arabidopsis.

PMID- 12068103
TI  - SOS4, a pyridoxal kinase gene, is required for root hair development in
      Arabidopsis.
AB  - Root hair development in plants is controlled by many genetic, hormonal, and
      environmental factors. A number of genes have been shown to be important for root
      hair formation. Arabidopsis salt overly sensitive 4 mutants were originally
      identified by screening for NaCl-hypersensitive growth. The SOS4 (Salt Overly
      Sensitive 4) gene was recently isolated by map-based cloning and shown to encode
      a pyridoxal (PL) kinase involved in the production of PL-5-phosphate, which is an
      important cofactor for various enzymes and a ligand for certain ion transporters.
      The root growth of sos4 mutants is slower than that of the wild type. Microscopic
      observations revealed that sos4 mutants do not have root hairs in the maturation
      zone. The sos4 mutations block the initiation of most root hairs, and impair the
      tip growth of those that are initiated. The root hairless phenotype of sos4
      mutants was complemented by the wild-type SOS4 gene. SOS4 promoter-beta
      glucuronidase analysis showed that SOS4 is expressed in the root hair and other
      hair-like structures. Consistent with SOS4 function as a PL kinase, in vitro
      application of pyridoxine and pyridoxamine, but not PL, partially rescued the
      root hair defect in sos4 mutants. 1-Aminocyclopropane-1-carboxylic acid and 2,4
      dichlorophenoxyacetic acid treatments promoted root hair formation in both wild
      type and sos4 plants, indicating that genetically SOS4 functions upstream of
      ethylene and auxin in root hair development. The possible role of SOS4 in
      ethylene and auxin biosynthesis is discussed.

PMID- 12068104
TI  - The pgp1 mutant locus of Arabidopsis encodes a phosphatidylglycerolphosphate
      synthase with impaired activity.
AB  - Phosphatidylglycerol is a ubiquitous phospholipid that is also present in the
      photosynthetic membranes of plants. Multiple independent lines of evidence
      suggest that this lipid plays a critical role for the proper function of
      photosynthetic membranes and cold acclimation. In eukaryotes, different
      subcellular compartments are competent for the biosynthesis of
      phosphatidylglycerol. Details on the plant-specific pathways in different
      organelles are scarce. Here, we describe a phosphatidylglycerol biosynthesis
      deficient mutant of Arabidopsis, pgp1. The overall content of
      phosphatidylglycerol is reduced by 30%. This mutant carries a point mutation in
      the CDP-alcohol phosphotransferase motif of the phosphatidylglycerolphosphate
      synthase (EC 2.7.8.5) isoform encoded by a gene on chromosome 2. The mutant shows
      an 80% reduction in plastidic phosphatidylglycerolphosphate synthase activity
      consistent with the plastidic location of this particular isoform. Mutant plants
      are pale green, and their photosynthesis is impaired. This mutant provides a
      promising new tool to elucidate the biosynthesis and function of plastidic
      phosphatidylglycerol in seed plants.

PMID- 12068106
TI  - Single and double knockouts of the genes for photosystem I subunits G, K, and H
      of Arabidopsis. Effects on photosystem I composition, photosynthetic electron
      flow, and state transitions.
AB  - Photosystem I (PSI) of higher plants contains 18 subunits. Using Arabidopsis En
      insertion lines, we have isolated knockout alleles of the genes psaG, psaH2, and
      psaK, which code for PSI-G, -H, and -K. In the mutants psak-1 and psag-1.4,
      complete loss of PSI-K and -G, respectively, was confirmed, whereas the residual
      H level in psah2-1.4 is due to a second gene encoding PSI-H, psaH1. Double
      mutants, lacking PSI-G, and also -K, or a fraction of -H, together with the three
      single mutants were characterized for their growth phenotypes and PSI polypeptide
      composition. In general, the loss of each subunit has secondary, in some cases
      additive, effects on the abundance of other PSI polypeptides, such as D, E, H, L,
      N, and the light-harvesting complex I proteins Lhca2 and 3. In the G-less mutant
      psag-1.4, the variation in PSI composition suggests that PSI-G stabilizes the PSI
      core. Levels of light-harvesting complex I proteins in plants, which lack
      simultaneously PSI-G and -K, indicate that PSI subunits other than G and K can
      also bind Lhca2 and 3. In the same single and double mutants, psag-1.4, psak-1,
      psah2-1.4, psag-1.4/psah2-1.4, and psag-1.4/psak-1 photosynthetic electron flow
      and excitation energy quenching were analyzed to address the roles of the various
      subunits in P700 reduction (mediated by PSI-F and -N) and oxidation (PSI-E), and
      state transitions (PSI-H). Based on the results, we also suggest for PSI-K a role
      in state transitions.

PMID- 12068105
TI  - SPINDLY is a nuclear-localized repressor of gibberellin signal transduction
      expressed throughout the plant.
AB  - SPY (SPINDLY) encodes a putative O-linked N-acetyl-glucosamine transferase that
      is genetically defined as a negatively acting component of the gibberellin (GA)
      signal transduction pathway. Analysis of Arabidopsis plants containing a SPY::GUS
      reporter gene reveals that SPY is expressed throughout the life of the plant and
      in most plant organs examined. In addition to being expressed in all organs where
      phenotypes due to spy mutations have been reported, SPY::GUS is expressed in the
      root. Examination of the roots of wild-type, spy, and gai plants revealed
      phenotypes indicating that SPY and GAI play a role in root development. A second
      SPY::GUS reporter gene lacking part of the SPY promoter was inactive, suggesting
      that sequences in the first exon and/or intron are required for detectable
      expression. Using both subcellular fractionation and visualization of a SPY-green
      fluorescent protein fusion protein that is able to rescue the spy mutant
      phenotype, the majority of SPY protein was shown to be present in the nucleus.
      This result is consistent with the nuclear localization of other components of
      the GA response pathway and suggests that SPY's role as a negative regulator of
      GA signaling involves interaction with other nuclear proteins and/or O-N-acetyl
      glucosamine modification of these proteins.

PMID- 12068108
TI  - Regulation of the cell expansion gene RHD3 during Arabidopsis development.
AB  - The RHD3 (ROOT HAIR DEFECTIVE3) gene encodes a putative GTP-binding protein
      required for appropriate cell enlargement in Arabidopsis. To obtain insight into
      the mechanisms of RHD3 regulation, we conducted a molecular genetic dissection of
      RHD3 gene expression and function. Gene fusion and complementation studies show
      that the RHD3 gene is highly expressed throughout Arabidopsis development and is
      controlled by two major regulatory regions. One regulatory region is located
      between -1,500 and -600 bp upstream of the RHD3 gene and is required for vascular
      tissue expression. The other region is intragenically located and includes the
      558-bp first intron, which is responsible for high-level expression of RHD3
      throughout the plant. The presence and location of this intron is essential for
      gene function because constructs lacking this intron or constructs with the
      intron in an abnormal position are unable to functionally complement the rhd3
      mutations. We also analyzed the role of other RHD genes and the plant hormones
      auxin and ethylene in RHD3 regulation, and we determined that these act
      downstream or independently from the RHD3 pathway. This study shows that multiple
      levels of regulation are employed to ensure the appropriate expression of RHD3
      throughout Arabidopsis development.

PMID- 12068107
TI  - Metabolic and environmental regulation of 3-methylcrotonyl-coenzyme A carboxylase
      expression in Arabidopsis.
AB  - 3-Methylcrotonyl-coenzyme A carboxylase (MCCase) is a nuclear-encoded,
      mitochondrial biotin-containing enzyme composed of two types of subunits: the
      biotinylated MCC-A subunit (encoded by the gene At1g03090) and the non
      biotinylated MCC-B subunit (encoded by the gene At4g34030). The major metabolic
      role of MCCase is in the mitochondrial catabolism of leucine, and it also might
      function in the catabolism of isoprenoids and the mevalonate shunt. In the work
      presented herein, the single-copy gene encoding the Arabidopsis MCC-A subunit was
      isolated and characterized. It contains 15 exons separated by 14 introns. We
      examined the expression of the single-copy MCC-A and MCC-B genes in Arabidopsis
      by monitoring the accumulation of the two protein and mRNA products. In addition,
      the expression of these two genes was studied in transgenic plants containing the
      1.1- and 1.0-kb 5' upstream sequences of the two MCCase subunit genes,
      respectively, fused to the beta-glucuronidase gene. Light deprivation induces
      MCCase expression, which is suppressed by exogenous carbohydrates, especially
      sucrose. Several lines of evidence indicate that the suppressor of MCCase
      expression is synthesized in illuminated photosynthetic organs, and can be
      translocated to other organs to regulate MCCase expression. These results are
      consistent with the hypothesis that the suppressor of MCCase expression is a
      carbohydrate, perhaps sucrose or a carbohydrate metabolite. We conclude that
      MCCase expression is primarily controlled at the level of gene transcription and
      regulated by a complex interplay between environmental and metabolic signals. The
      observed expression patterns may indicate that one of the physiological roles of
      MCCase is to maintain the carbon status of the organism, possibly via the
      catabolism of leucine.

PMID- 12068109
TI  - Molecular and physiological analysis of Arabidopsis mutants defective in
      cytosolic or chloroplastic aspartate aminotransferase.
AB  - Arabidopsis mutants deficient in cytosolic (AAT2) or chloroplastic (AAT3)
      aspartate (Asp) aminotransferase were characterized at the molecular and
      physiological levels. All of the ethyl methane sulfonate- or nitrosomethylurea
      generated mutants are missense mutations, as determined by sequencing of the ASP2
      gene from the cytosolic aat2 mutants (aat2-1, aat2-2, aat2-4, and aat2-5) and the
      ASP5 gene from the chloroplastic aat3 mutants (aat3-1, aat3-2, and aat3-4). A T
      DNA insertion mutant in cytosolic AAT2 (aat2-T) was also identified. All the
      cytosolic aat2 and chloroplastic aat3 mutants have less than 6% AAT2 and less
      than 3% AAT3 activity, respectively, as determined by the native gel assay;
      however, none are nulls. The metabolic and physiological affect of these
      mutations in AAT isoenzymes was determined by measuring growth and amino acid
      levels in the aat mutants. Two aat2 mutants (aat2-2 and aat2-T) show reduced root
      length on Murashige and Skoog medium. For aat2-2, this growth defect is
      exaggerated by Asp supplementation, suggesting a defect in Asp metabolism. Amino
      acid analysis of the aat mutants showed alterations in levels of Asp and/or Asp
      derived amino acids in several aat2 alleles. Two aat2 mutants show dramatic
      decreases in Asp and asparagine levels in leaves and/or siliques. As such, the
      cytosolic AAT2 isoenzyme appears to serve a nonredundant function in plant
      nitrogen metabolism of Asp and Asp-derived amino acids.

PMID- 12068110
TI  - Transcriptional profiling reveals novel interactions between wounding, pathogen,
      abiotic stress, and hormonal responses in Arabidopsis.
AB  - Mechanical wounding not only damages plant tissues, but also provides pathways
      for pathogen invasion. To understand plant responses to wounding at a genomic
      level, we have surveyed the transcriptional response of 8,200 genes in
      Arabidopsis plants. Approximately 8% of these genes were altered by wounding at
      steady-state mRNA levels. Studies of expression patterns of these genes provide
      new information on the interactions between wounding and other signals, including
      pathogen attack, abiotic stress factors, and plant hormones. For example, a
      number of wound-responsive genes encode proteins involved in pathogen response.
      These include signaling molecules for the pathogen resistance pathway and enzymes
      required for cell wall modification and secondary metabolism. Many osmotic stress
      and heat shock-regulated genes were highly responsive to wounding. Although a
      number of genes involved in ethylene, jasmonic acid, and abscisic acid pathways
      were activated, many in auxin responses were suppressed by wounding. These
      results further dissected the nature of mechanical wounding as a stress signal
      and identified new genes that may play a role in wounding and other signal
      transduction pathways.

PMID- 12068111
TI  - Cytokinesis-defective mutants of Arabidopsis.
AB  - We have identified mutations in six previously uncharacterized genes of
      Arabidopsis, named club, bublina, massue, rod, bloated, and bims, that are
      required for cytokinesis. The mutants are seedling lethal, have morphological
      abnormalities, and are characterized by cell wall stubs, gapped walls, and
      multinucleate cells. In these and other respects, the new mutants are
      phenotypically similar to knolle, keule, hinkel, and pleiade mutants. The mutants
      display a gradient of stomatal phenotypes, correlating roughly with the severity
      of their cytokinesis defect. Similarly, the extent to which the different mutant
      lines were capable of growing in tissue culture correlated well with the severity
      of the cytokinesis defect. Phenotypic analysis of the novel and previously
      characterized loci indicated that the secondary consequences of a primary defect
      in cytokinesis include anomalies in body organization, organ number, and cellular
      differentiation, as well as organ fusions and perturbations of the nuclear cycle.
      Two of the 10 loci are required for both cytokinesis and root hair morphogenesis.
      The results have implications for the identification of novel cytokinesis genes
      and highlight the mechanistic similarity between cytokinesis and root hair
      morphogenesis, two processes that result in a rapid deposition of new cell walls
      via polarized secretion.

PMID- 12068112
TI  - RASPBERRY3 gene encodes a novel protein important for embryo development.
AB  - We identified a new gene that is interrupted by T-DNA in an Arabidopsis embryo
      mutant called raspberry3. raspberry3 has "raspberry-like" cellular protuberances
      with an enlarged suspensor characteristic of other raspberry embryo mutants, and
      is arrested morphologically at the globular stage of embryo development. The
      predicted RASPBERRY3 protein has domains found in proteins present in prokaryotes
      and algae chloroplasts. Computer prediction analysis suggests that the
      RASPBERRY3protein may be localized in the chloroplast. Complementation analysis
      supports the possibility that the RASPBERRY3 protein may be involved in
      chloroplast development. Our experiments demonstrate the important role of the
      chloroplast, directly or indirectly, in embryo morphogenesis and development.

PMID- 12068113
TI  - Potentiation of developmentally regulated plant defense response by AtWRKY18, a
      pathogen-induced Arabidopsis transcription factor.
AB  - AtWRKY18 is a pathogen- and salicylic acid-induced Arabidopsis transcription
      factor containing the plant-specific WRKY zinc finger DNA-binding motif. In the
      present study, we have transformed Arabidopsis plants with AtWRKY18 under control
      of the cauliflower mosaic virus 35S promoter. Surprisingly, transgenic plants
      expressing high levels of AtWRKY18 were stunted in growth. When expressed at
      moderate levels, AtWRKY18 potentiated developmentally regulated defense responses
      in transgenic plants without causing substantial negative effects on plant
      growth. As they grew from seedling to mature stages, transgenic AtWRKY18 plant
      showed marked increase in the expression of pathogenesis-related genes and
      resistance to the bacterial pathogen Pseudomonas syringae, whereas wild-type
      plants exhibited little enhancement in these defense responses. Potentiation of
      developmentally regulated defense responses by AtWRKY18 was not associated with
      enhanced biosynthesis of salicylic acid but required the disease resistance
      regulatory protein NPR1/NIM1. Thus, AtWRKY18 can positively modulate defense
      related gene expression and disease resistance. To study the regulated expression
      of AtWRKY18, we have identified a cluster of WRKY binding sites in the promoter
      of the gene and demonstrated that they acted as negative regulatory elements for
      the inducible expression of AtWRKY18. These negative cis-acting elements may
      prevent overexpression of AtWRKY18 during the activation of plant defense
      responses that could be detrimental to plant growth as inferred from the
      transgenic plants ectopically expressing the transgene.

PMID- 12068114
TI  - Evidence for a Ustilago maydis steroid 5alpha-reductase by functional expression
      in Arabidopsis det2-1 mutants.
AB  - We have identified a gene (udh1) in the basidiomycete Ustilago maydis that is
      induced during the parasitic interaction with its host plant maize (Zea mays).
      udh1 encodes a protein with high similarity to mammalian and plant 5alpha-steroid
      reductases. Udh1 differs from those of known 5alpha-steroid reductases by six
      additional domains, partially predicted to be membrane-spanning. A fusion protein
      of Udh1 and the green fluorescent protein provided evidence for endoplasmic
      reticulum localization in U. maydis. The function of the Udh1 protein was
      demonstrated by complementing Arabidopsis det2-1 mutants, which display a dwarf
      phenotype due to a mutation in the 5alpha-steroid reductase encoding DET2 gene.
      det2-1 mutant plants expressing either the udh1 or the DET2 gene controlled by
      the cauliflower mosaic virus 35S promoter differed from wild-type Columbia plants
      by accelerated stem growth, flower and seed development and a reduction in size
      and number of rosette leaves. The accelerated growth phenotype of udh1 transgenic
      plants was stably inherited and was favored under reduced light conditions.
      Truncation of the N-terminal 70 amino acids of the Udh1 protein abolished the
      ability to restore growth in det2-1 plants. Our results demonstrate the existence
      of a 5alpha-steroid reductase encoding gene in fungi and suggest a common
      ancestor between fungal, plant, and mammalian proteins.

PMID- 12068115
TI  - Remodeling of DNA methylation and phenotypic and transcriptional changes in
      synthetic Arabidopsis allotetraploids.
AB  - The joining of different genomes in allotetraploids played a major role in plant
      evolution, but the molecular implications of this event are poorly understood. In
      synthetic allotetraploids of Arabidopsis and Cardaminopsis arenosa, we previously
      demonstrated the occurrence of frequent gene silencing. To explore the
      involvement of epigenetic phenomena, we investigated the occurrence and effects
      of DNA methylation changes. Changes in DNA methylation patterns were more
      frequent in synthetic allotetraploids than in the parents. Treatment with 5-aza
      2'-deoxycytidine, an inhibitor of DNA methyltransferase, resulted in the
      development of altered morphologies in the synthetic allotetraploids, but not in
      the parents. We profiled mRNAs in control and 5-aza-2'-deoxycytidine-treated
      parents and allotetraploids by amplified fragment length polymorphism-cDNA. We
      show that DNA demethylation induced and repressed two different transcriptomes.
      Our results are consistent with the hypothesis that synthetic allotetraploids
      have compromised mechanisms of epigenetic gene regulation.

PMID- 12068116
TI  - The lateral organ boundaries gene defines a novel, plant-specific gene family.
AB  - The LATERAL ORGAN BOUNDARIES (LOB) gene in Arabidopsis defines a new conserved
      protein domain. LOB is expressed in a band of cells at the adaxial base of all
      lateral organs formed from the shoot apical meristem and at the base of lateral
      roots. LOB encodes a predicted protein that does not have recognizable functional
      motifs, but that contains a conserved domain (the LOB domain) that is present in
      42 other Arabidopsis proteins and in proteins from a variety of other plant
      species. Proteins showing similarity to the LOB domain were not found outside of
      plant databases, indicating that this unique protein may play a role in plant
      specific processes. Genes encoding LOB domain proteins are expressed in a variety
      of temporal- and tissue-specific patterns, suggesting that they may function in
      diverse processes. Loss-of-function LOB mutants have no detectable phenotype
      under standard growth conditions, suggesting that LOB is functionally redundant
      or required during growth under specific environmental conditions. Ectopic
      expression of LOB leads to alterations in the size and shape of leaves and floral
      organs and causes male and female sterility. The expression of LOB at the base of
      lateral organs suggests a potential role for LOB in lateral organ development.

PMID- 12068117
TI  - Photochemical properties of the flavin mononucleotide-binding domains of the
      phototropins from Arabidopsis, rice, and Chlamydomonas reinhardtii.
AB  - Phototropins (phot1 and phot2, formerly designated nph1 and npl1) are blue-light
      receptors that mediate phototropism, blue light-induced chloroplast relocation,
      and blue light-induced stomatal opening in Arabidopsis. Phototropins contain two
      light, oxygen, or voltage (LOV) domains at their N termini (LOV1 and LOV2), each
      a binding site for the chromophore flavin mononucleotide (FMN). Their C termini
      contain a serine/threonine protein kinase domain. Here, we examine the kinetic
      properties of the LOV domains of Arabidopsis phot1 and phot2, rice (Oryza sativa)
      phot1 and phot2, and Chlamydomonas reinhardtii phot. When expressed in
      Escherichia coli, purified LOV domains from all phototropins examined bind FMN
      tightly and undergo a self-contained photocycle, characterized by fluorescence
      and absorption changes induced by blue light (T. Sakai, T. Kagawa, M. Kasahara,
      T.E. Swartz, J.M. Christie, W.R. Briggs, M. Wada, K. Okada [2001] Proc Natl Acad
      Sci USA 98: 6969-6974; M. Salomon, J.M. Christie, E. Knieb, U. Lempert, W.R.
      Briggs [2000] Biochemistry 39: 9401-9410). The photocycle involves the light
      induced formation of a cysteinyl adduct to the C(4a) carbon of the FMN
      chromophore, which subsequently breaks down in darkness. In each case, the
      relative quantum efficiencies for the photoreaction and the rate constants for
      dark recovery of LOV1, LOV2, and peptides containing both LOV domains are
      presented. Moreover, the data obtained from full-length Arabidopsis phot1 and
      phot2 expressed in insect cells closely resemble those obtained for the tandem
      LOV-domain fusion proteins expressed in E. coli. For both Arabidopsis and rice
      phototropins, the LOV domains of phot1 differ from those of phot2 in their
      reaction kinetic properties and relative quantum efficiencies. Thus, in addition
      to differing in amino acid sequence, the phototropins can be distinguished on the
      basis of the photochemical cycles of their LOV domains. The LOV domains of C.
      reinhardtii phot also undergo light-activated spectral changes consistent with
      cysteinyl adduct formation. Thus, the phototropin family extends over a wide
      evolutionary range from unicellular algae to higher plants.

PMID- 12068119
TI  - Reorientation of seedlings in the earth's gravitational field induces cytosolic
      calcium transients.
AB  - The gravitational field controls plant growth, morphology, and development.
      However, the underlying transduction mechanisms are not well understood. Much
      indirect evidence has implicated the cytoplasmic free calcium concentration
      ([Ca(2+)](c)) as an important factor, but direct evidence for changes in
      [Ca(2+)](c) is currently lacking. We now have made measurements of [Ca(2+)](c) in
      groups of young seedlings of Arabidopsis expressing aequorin in the cytoplasm and
      reconstituted in vivo with cp-coelenterazine, a synthetic high-affinity
      luminophore. Distinct [Ca(2+)](c) signaling occurs in response to
      gravistimulation with kinetics very different from [Ca(2+)](c) transients evoked
      by other mechanical stimuli (e.g. movement and wind). [Ca(2+)](c) changes
      produced in response to gravistimulation are transient but with a duration of
      many minutes and dependent on stimulus strength (i.e. the angle of displacement).
      The auxin transport blockers 2,3,5-tri-iodo benzoic acid and N-(1-naphthyl)
      phthalamic acid interfere with gravi-induced [Ca(2+)](c) responses and addition
      of methyl indole-3-acetic acid to whole seedlings induces long-lived [Ca(2+)](c)
      transients, suggesting that changes in auxin transport may interact with
      [Ca(2+)](c). Permanent nonaxial rotation of seedlings on a two-dimensional
      clinostat, however, produced a sustained elevation of the [Ca(2+)](c) level. This
      probably reflects permanent displacement of gravity-sensing cellular components
      and/or disturbance of cytoskeletal tension. It is concluded that [Ca(2+)](c) is
      part of the gravity transduction mechanism in young Arabidopsis seedlings.

PMID- 12068118
TI  - Action spectrum for cryptochrome-dependent hypocotyl growth inhibition in
      Arabidopsis.
AB  - Cryptochrome blue-light photoreceptors are found in both plants and animals and
      have been implicated in numerous developmental and circadian signaling pathways.
      Nevertheless, no action spectrum for a physiological response shown to be
      entirely under the control of cryptochrome has been reported. In this work, an
      action spectrum was determined in vivo for a cryptochrome-mediated high
      irradiance response, the blue-light-dependent inhibition of hypocotyl elongation
      in Arabidopsis. Comparison of growth of wild-type, cry1cry2 cryptochrome
      deficient double mutants, and cryptochrome-overexpressing seedlings demonstrated
      that responsivity to monochromatic light sources within the range of 390 to 530
      nm results from the activity of cryptochrome with no other photoreceptor having a
      significant primary role at the fluence range tested. In both green- and
      norflurazon-treated (chlorophyll-deficient) seedlings, cryptochrome activity is
      fairly uniform throughout its range of maximal response (390-480 nm), with no
      sharply defined peak at 450 nm; however, activity at longer wavelengths was
      disproportionately enhanced in CRY1-overexpressing seedlings as compared with
      wild type. The action spectrum does not correlate well with the absorption
      spectra either of purified recombinant cryptochrome photoreceptor or to that of a
      second class of blue-light photoreceptor, phototropin (PHOT1 and PHOT2).
      Photoreceptor concentration as determined by western-blot analysis showed a
      greater stability of CRY2 protein under the monochromatic light conditions used
      in this study as compared with broad band blue light, suggesting a complex
      mechanism of photoreceptor activation. The possible role of additional
      photoreceptors (in particular phytochrome A) in cryptochrome responses is
      discussed.

PMID- 12068120
TI  - Functional analysis of the cellulose synthase genes CesA1, CesA2, and CesA3 in
      Arabidopsis.
AB  - Polysaccharide analyses of mutants link several of the glycosyltransferases
      encoded by the 10 CesA genes of Arabidopsis to cellulose synthesis. Features of
      those mutant phenotypes point to particular genes depositing cellulose
      predominantly in either primary or secondary walls. We used transformation with
      antisense constructs to investigate the functions of CesA2 (AthA) and CesA3
      (AthB), genes for which reduced synthesis mutants are not yet available. Plants
      expressing antisense CesA1 (RSW1) provided a comparison with a gene whose mutant
      phenotype (Rsw1(-)) points mainly to a primary wall role. The antisense
      phenotypes of CesA1 and CesA3 were closely similar and correlated with reduced
      expression of the target gene. Reductions in cell length rather than cell number
      underlay the shorter bolts and stamen filaments. Surprisingly, seedling roots
      were unaffected in both CesA1 and CesA3 antisense plants. In keeping with the
      mild phenotype compared with Rsw1(-), reductions in total cellulose levels in
      antisense CesA1 and CesA3 plants were at the borderline of significance. We
      conclude that CesA3, like CesA1, is required for deposition of primary wall
      cellulose. To test whether there were important functional differences between
      the two, we overexpressed CesA3 in rsw1 but were unable to complement that
      mutant's defect in CesA1. The function of CesA2 was less obvious, but, consistent
      with a role in primary wall deposition, the rate of stem elongation was reduced
      in antisense plants growing rapidly at 31 degrees C.

PMID- 12068121
TI  - Molecular characterization and evolution of the protein phosphatase 2A B'
      regulatory subunit family in plants.
AB  - Type 2A serine/threonine protein phosphatases (PP2A) are important components in
      the reversible protein phosphorylation events in plants and other organisms. PP2A
      proteins are oligomeric complexes constituted by a catalytic subunit and several
      regulatory subunits that modulate the activity of these phosphatases. The
      analysis of the complete genome of Arabidopsis allowed us to characterize four
      novel genes, AtB'epsilon, AtB'zeta, AtB'eta, and AtB'theta;, belonging to the
      PP2A B' regulatory subunit family. Because four genes of this type had been
      described previously, this family is composed of eight members. Reverse
      transcriptase-polymerase chain reaction experiments showed that AtB'epsilon mRNAs
      are present in all Arabidopsis tissues analyzed, and their levels do not respond
      significantly to heat stress. Expressed sequence tags corresponding to AtB'zeta,
      AtB'eta, and AtB'theta; have been identified, indicating that the new genes are
      actively transcribed. The genomic organization of this family of PP2A regulatory
      subunits is reported, as well as its chromosomal location. An extensive survey of
      the family has been carried out in plants, characterizing B' subunits in a number
      of different species, and performing a phylogenetic study that included several
      B' regulatory proteins from animals. Our results indicate that the animal and
      plant proteins have evolved independently, that there is a relationship between
      the number of B' isoforms and the complexity of the organism, and that there are
      at least three main subfamilies of regulatory subunits in plants, which we have
      named alpha, eta, and kappa.

PMID- 12068122
TI  - Proteomics of Arabidopsis seed germination. A comparative study of wild-type and
      gibberellin-deficient seeds.
AB  - We examined the role of gibberellins (GAs) in germination of Arabidopsis seeds by
      a proteomic approach. For that purpose, we used two systems. The first system
      consisted of seeds of the GA-deficient ga1 mutant, and the second corresponded to
      wild-type seeds incubated in paclobutrazol, a specific GA biosynthesis inhibitor.
      With both systems, radicle protrusion was strictly dependent on exogenous GAs.
      The proteomic analysis indicated that GAs do not participate in many processes
      involved in germination sensu stricto (prior to radicle protrusion), as, for
      example, the initial mobilization of seed protein and lipid reserves. Out of 46
      protein changes detected during germination sensu stricto (1 d of incubation on
      water), only one, corresponding to the cytoskeleton component alpha-2,4 tubulin,
      appeared to depend on the action of GAs. An increase in this protein spot was
      noted for the wild-type seeds but not for the ga1 seeds incubated for 1 d on
      water. In contrast, GAs appeared to be involved, directly or indirectly, in
      controlling the abundance of several proteins associated with radicle protrusion.
      This is the case for two isoforms of S-adenosyl-methionine (Ado-Met) synthetase,
      which catalyzes the formation of Ado-Met from Met and ATP. Owing to the
      housekeeping functions of Ado-Met, this event is presumably required for
      germination and seedling establishment, and might represent a major metabolic
      control of seedling establishment. GAs can also play a role in controlling the
      abundance of a beta-glucosidase, which might be involved in the embryo cell wall
      loosening needed for cell elongation and radicle extension.

PMID- 12068123
TI  - Heat stress- and heat shock transcription factor-dependent expression and
      activity of ascorbate peroxidase in Arabidopsis.
AB  - To find evidence for a connection between heat stress response, oxidative stress,
      and common stress tolerance, we studied the effects of elevated growth
      temperatures and heat stress on the activity and expression of ascorbate
      peroxidase (APX). We compared wild-type Arabidopsis with transgenic plants
      overexpressing heat shock transcription factor 3 (HSF3), which synthesize heat
      shock proteins and are improved in basal thermotolerance. Following heat stress,
      APX activity was positively affected in transgenic plants and correlated with a
      new thermostable isoform, APX(S). This enzyme was present in addition to
      thermolabile cytosolic APX1, the prevalent isoform in unstressed cells. In HSF3
      transgenic plants, APX(S) activity was detectable at normal temperature and
      persisted after severe heat stress at 44 degrees C. In nontransgenic plants,
      APX(S) was undetectable at normal temperature, but could be induced by moderate
      heat stress. The mRNA expression profiles of known and three new Apx genes were
      determined using real-time PCR. Apx1 and Apx2 genes encoding cytosolic APX were
      heat stress and HSF dependently expressed, but only the representations of Apx2
      mRNA met the criteria that suggest identity between APX(S) and APX2: not
      expressed at normal temperature in wild type, strong induction by heat stress,
      and HSF3-dependent expression in transgenic plants. Our data suggest that Apx2 is
      a novel heat shock gene and that the enzymatic activity of APX2/APX(S) is
      required to compensate heat stress-dependent decline of APX1 activity in the
      cytosol. The functional roles of modulations of APX expression and the
      interdependence of heat stress and oxidative stress response and signaling
      mechanisms are discussed.

PMID- 12068125
TI  - Genetic control of male germ unit organization in Arabidopsis.
AB  - In flowering plants, the vegetative nucleus and the two sperm cells are proposed
      to form a functional assemblage, the male germ unit (MGU). Here, we describe the
      developmental pathway of MGU assembly in Arabidopsis and report two classes of
      mutations that affect the integrity and/or the positioning of the MGU in the
      mature pollen grain. In germ unit malformed (gum) mutants, the vegetative nucleus
      is positioned adjacent to the pollen grain wall, separate from the two sperm
      cells, whereas in MGU displaced (mud) mutants, the intact MGU is displaced to the
      pollen grain wall. mud and gum mutants correspond to male-specific gametophytic
      mutations that also reduce pollen fitness. Genetic mapping showed that the gum1
      and gum2 mutations are genetically linked, possibly allelic, whereas the mud1 and
      mud2 mutations correspond to two unlinked loci mapping on different chromosomes.
      The hierarchical relationship between mud and gum mutations was investigated by
      phenotypic analysis of double mutants. gum1 appeared to act earlier than mud1 and
      mud2, affecting initial MGU assembly and its stability during pollen maturation.
      In contrast, mud1 and mud2 mutations appear to act only on MGU positioning during
      final maturation. From in planta analyses of pollen germination in mud and gum
      mutants, we conclude that the initial proximity and positioning of MGU components
      is not required for their entrance into the pollen tube, but the efficiency of
      MGU translocation is reduced.

PMID- 12068124
TI  - Variation in growth rate between Arabidopsis ecotypes is correlated with cell
      division and A-type cyclin-dependent kinase activity.
AB  - We used a kinematic analysis to investigate the growth processes responsible for
      variation in primary root growth between 18 ecotypes of Arabidopsis. Root
      elongation rate differed 4-fold between the slowest (Landsberg erecta, 71 microm
      h(-1)) and fastest growing line (Wassilewskija [Ws]; 338 microm h(-1)). This
      difference was contributed almost equally by variations in mature cortical cell
      length (84 microm [Landsberg erecta] to 237 microm [Ws]) and rate of cell
      production (0.63 cell h(-1) [NW108] to 1.83 cell h(-1) [Ws]). Cell production, in
      turn, was determined by variation in cell cycle duration (19 h [Tsu] to 48 h
      [NW108]) and, to a lesser extent, by differences in the number of dividing cells
      (32 [Weiningen] to 61 [Ws]). We found no correlation between mature cell size and
      endoreduplication, refuting the hypothesis that the two are linked. However,
      there was a strong correlation between cell production rates and the activity of
      the cyclin-dependent kinase (CDKA). The level of the protein could explain 32% of
      the variation in CDKA. Therefore, it is likely that regulators of CDKA, such as
      cyclins and inhibitors, are also involved. These data provide a functional link
      between cell cycle regulation and whole-plant growth rate as affected by genetic
      differences.

PMID- 12068126
TI  - Photoinhibition in mutants of Arabidopsis deficient in thylakoid unsaturation.
AB  - Thylakoid lipid composition in higher plants is characterized by a high level of
      fatty acid unsaturation. We have screened four mutants of Arabidopsis that have
      reduced levels of fatty acid unsaturation. Three of the mutant lines tested,
      fad5, fad6, and the fad3-2 fad7-2 fad8 triple mutant, were more susceptible to
      photoinhibition than wild-type Arabidopsis, whereas one mutant, fab1, was
      indistinguishable from wild type. The fad3-2 fad7-2 fad8 triple mutant, which
      contains no trienoic fatty acids in its thylakoid membranes, was most susceptible
      to photoinhibition. Detailed investigation of photoinhibition in the triple
      mutant revealed that the rate of photoinactivation of PSII was the same in wild
      type and mutant plants. However, the recovery of photoinactivated PSII was slower
      in fad3-2 fad7-2 fad8, relative to wild type, at all temperatures below 27
      degrees C. These results indicate that trienoic fatty acids of thylakoid membrane
      lipids are required for low-temperature recovery from photoinhibition in
      Arabidopsis.

PMID- 12068127
TI  - Analysis of the NRT2 nitrate transporter family in Arabidopsis. Structure and
      gene expression.
AB  - Nitrate is an essential element for plant growth, both as a primary nutrient in
      the nitrogen assimilation pathway and as an important signal for plant
      development. The uptake of nitrate from the soil and its translocation throughout
      the plant has been the subject of intensive physiological and molecular studies.
      Using a reverse genetic approach, the AtNRT2.1 gene has been shown to be involved
      in the inducible component of the high-affinity nitrate transport system in
      Arabidopsis. The Arabidopsis Genome Initiative has released nearly the whole
      genome sequence of Arabidopsis, allowing the identification of a small NRT2
      multigene family in this species. Thus, we investigated the phylogenetic
      relationship between NRT2 proteins belonging to several kingdoms and compared the
      structure of the different members of the Arabidopsis family. We analyzed, by
      semiquantitative reverse transcriptase-polymerase chain reaction, the expression
      pattern of each gene depending on plant organ and development or nutritional
      status, and compared the relative level of each gene by real-time polymerase
      chain reaction. We also evaluated the significance of each paralog on the basis
      of the relative levels of gene expression. The results are discussed in relation
      with distinct roles for the individual members of the AtNRT2 family.

PMID- 12068128
TI  - Role of a heterotrimeric G protein in regulation of Arabidopsis seed germination.
AB  - Seed germination is regulated by many signals. We investigated the possible
      involvement of a heterotrimeric G protein complex in this signal regulation.
      Seeds that carry a protein null mutation in the gene encoding the alpha subunit
      of the G protein in Arabidopsis (GPA1) are 100-fold less responsive to
      gibberellic acid (GA), have increased sensitivity to high levels of Glc, and have
      a near-wild-type germination response to abscisic acid and ethylene, indicating
      that GPA1 does not directly couple these signals in germination control. Seeds
      ectopically expressing GPA1 are at least a million-fold more responsive to GA,
      yet still require GA for germination. We conclude that the GPA1 indirectly
      operates on the GA pathway to control germination by potentiation. We propose
      that this potentiation is directly mediated by brassinosteroids (BR) because the
      BR response and synthesis mutants, bri1-5 and det2-1, respectively, share the
      same GA sensitivity as gpa1 seeds. Furthermore, gpa1 seeds are completely
      insensitive to brassinolide rescue of germination when the level of GA in seeds
      is reduced. A lack of BR responsiveness is also apparent in gpa1 roots and
      hypocotyls suggesting that BR signal transduction is likely coupled by a
      heterotrimeric G protein at various points in plant development.

PMID- 12068130
TI  - Clinical applications of TSH receptor antibodies in thyroid diseases.
AB  - The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR),
      combined with advances in molecular techniques, have facilitated the
      understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR
      at the molecular level and have allowed the delineation of their clinical role.
      TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause
      hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the
      blocking TSHRAbs cause hypothyroidism in some patients with autoimmune
      hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring
      TSHRAbs has potential clinical implications in differential diagnosis of Graves'
      disease, predicting the outcome of Graves' disease after antithyroid drug
      treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal
      hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of
      stimulating TSHRAbs with epitopes other than on the N-terminal region of the
      extracellular domain, is significantly associated with favorable long-term
      clinical response to antithyroid drug treatment. Measuring these subtypes for
      thyroid-stimulating antibody (TSAb) has potential clinical implications, for
      example, in predicting responsiveness to treatment in untreated patients with
      Graves' disease.

PMID- 12068131
TI  - The effect of the repeated subcultures of Helicobacter pylori on adhesion,
      motility, cytotoxicity, and gastric inflammation.
AB  - In vitro subcultures of bacteria can lead to genetic and phenotypic changes. This
      study aimed at investigating the effect of repeated subcultures on the adhesion,
      motility, cytotoxicity, and gastric inflammation caused by Helicobacter pylori.
      H.pylori SS1 strain was subcultured 64 times on agar plates containing Brucella
      broth and 5% bovine calf serum. The adhesion, motility, cytotoxicity, and gastric
      inflammation produced in Mongolian gerbils were compared between the first and
      64th subcultured strain. The adhesion rates, following 3 hr exposure of AGS cells
      to either the first strain or the 64th-transferred strain, were 21% and 12%,
      respectively. The motility of the 64th-transferred strain decreased significantly
      when compared to the 1st strain (9.1 mm vs. 15.1 mm). The cytotoxicity index
      tended to be higher in the first strain than in the 64th-transferred strain
      (73.7% vs. 69.2%). The initial infection rate on the gerbils showed no difference
      between the two strains. However, chronic gastric inflammation of the first
      strain-infected gerbils was somewhat more severe than that of the 64th
      transferred strain-infected gerbils. Therefore, the use of repeatedly subcultured
      strains of H. pylori in virulence experiments can lead to different results from
      those of the original strain.

PMID- 12068129
TI  - The complement of protein phosphatase catalytic subunits encoded in the genome of
      Arabidopsis.
AB  - Reversible protein phosphorylation is critically important in the modulation of a
      wide variety of cellular functions. Several families of protein phosphatases
      remove phosphate groups placed on key cellular proteins by protein kinases. The
      complete genomic sequence of the model plant Arabidopsis permits a comprehensive
      survey of the phosphatases encoded by this organism. Several errors in the
      sequencing project gene models were found via analysis of predicted phosphatase
      coding sequences. Structural sequence probes from aligned and unaligned sequence
      models, and all-against-all BLAST searches, were used to identify 112 phosphatase
      catalytic subunit sequences, distributed among the serine (Ser)/threonine (Thr)
      phosphatases (STs) of the protein phosphatase P (PPP) family, STs of the protein
      phosphatase M (PPM) family (protein phosphatases 2C [PP2Cs] subfamily), protein
      tyrosine (Tyr) phosphatases (PTPs), low-M(r) protein Tyr phosphatases, and dual
      specificity (Tyr and Ser/Thr) phosphatases (DSPs). The Arabidopsis genome
      contains an abundance of PP2Cs (69) and a dearth of PTPs (one). Eight sequences
      were identified as new protein phosphatase candidates: five dual-specificity
      phosphatases and three PP2Cs. We used phylogenetic analyses to infer clustering
      patterns reflecting sequence similarity and evolutionary ancestry. These
      clusters, particularly for the largely unexplored PP2C set, will be a rich source
      of material for plant biologists, allowing the systematic sampling of protein
      function by genetic and biochemical means.

PMID- 12068133
TI  - Benzo[a]pyrene-induced DNA-protein crosslinks in cultured human lymphocytes and
      the role of the GSTM1 and GSTT1 genotypes.
AB  - We investigated the influence of glutathione S-transferase M1 (GSTM1) and
      glutathione S-transferase T1 (GSTT1) polymorphisms upon DNA-protein crosslinks
      (DPC) induced by benzo[a]pyrene (B[a]P) in cultured human lymphocytes. Lymphocyte
      samples were collected from 30 healthy nonsmoking hospital administrative
      workers. DPC was detected with KCl-SDS assay and the distributions of GSTM1 and
      GSTT1 were determined by polymerase chain reaction. B[a]P was found to induce a
      significant dose-responsive increase in cytotoxicity and DPC regardless of the
      genotypes (p<0.05). We did not find statistically significant genetic
      modification effect of GSTM1 and GSTT1 polymorphisms in the cytotoxicity and DPC
      formation (p>0.05). In terms of the genes examined, the level of cytotoxicity and
      DPC formation were found to be highest in the GSTM1-null and GSTT1-null cells. In
      conclusion, B[a]P induced a significant increase in the cytotoxicity and the
      level of DPC formation in cultured human lymphocytes. Our findings suggest that
      DPC could be used as a biomarker of B[a]P exposure.

PMID- 12068132
TI  - The effect of dietary intervention through the modification of fatty acids
      composition and antioxidant vitamin intake on plasma TXB(2) level in Korean
      postmenopausal women with hypercholesterolemia.
AB  - The purpose of this study was to observe the effects of dietary intervention,
      through the modification of dietary fatty acids composition and antioxidant
      vitamins, on plasma thromboxane B(2) (TXB(2)) levels in postmenopausal women with
      hypercholesterolemia. The subjects were treated for 12 weeks with one of three
      methods: hormone replacement therapy (HRT group, n=8), dietary intervention (DIET
      group, n=8), or HRT combined with dietary intervention (HRT +DIET group, n=8).
      Changes in serum phospholipid fatty acids composition, serum peroxides, and
      plasma TXB(2) levels were measured at weeks 0, 4 and 12. The P/S ratio increased
      and the n-6/ n-3 ratio decreased in the DIET and the HRT +DIET group at week 4
      (p<0.05). The ratio of C20:5/C20:4 in serum phospholipid increased in the DIET
      (p<0.05) and the HRT +DIET groups (NS) at week 4. Plasma TXB(2) levels decreased
      in the DIET (-35%, p<0.05) and the HRT +DIET groups (-18.8%, NS) at week 4. Serum
      lipid peroxides levels significantly decreased by 10.5% and 15.2% in the DIET
      group at weeks 4 and 12, and by 10.8% in the HRT +DIET group only at week 12
      (p<0.05). Dietary intervention may lower thrombotic risks in Korean
      postmenopausal women by changing the serum fatty acid composition, serum lipid
      peroxides levels and plasma thromboxane B(2) levels.

PMID- 12068134
TI  - Expression of cyclin B1 and cdc2 in nodal non-Hodgkin's lymphoma and its
      prognostic implications.
AB  - To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression
      of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined
      about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by
      immunohistochemical method. The correlation of their expression with various
      clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely
      expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied,
      respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant
      lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin
      B1 and cdc2 were expressed predominantly in the germinal center with mean
      labeling indices of 13.9% and 28.3%, respectively. The correlation between the
      expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was
      correlated with that of cyclin B1 (p=0.023) and marginally correlated with that
      of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to
      chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049).
      In multivariate analysis, the clinical stage alone showed significance on overall
      survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in
      the genesis or progression of malignant lymphoma and cdc2 can be a useful marker
      for response to chemotherapy.

PMID- 12068135
TI  - A nested case-control study on the high-normal blood pressure as a risk factor of
      hypertension in Korean middle-aged men.
AB  - The aim of this study was to identify the 'high-normal blood pressure' as a risk
      factor of hypertension for applying primary prevention strategy in Korean people.
      To keep time sequence of events, and to prevent information bias, nested case
      control study was chosen for avoiding measurement errors because hypertension is
      a benign disease. Source population consisted of the 'Seoul Cohort' participants
      and follow-up was done by using Korea Medical Insurance Corporation's database on
      the utilization of health services from January 1, 1993 to June 30, 1997.
      Incidence cases were ascertained through the chart review, telephone contacts,
      and direct blood pressure measurements. Controls included the pairing of 4
      individuals to each case on the basis of age. The statistically significant risk
      factors of hypertension were body mass index, dietary fiber, alcohol consumption,
      weekly activity, and history of quitting smoking as well as high-normal blood
      pressure (p<0.05). The multivariate odds ratio of high-normal blood pressure
      adjusted for all risk factors was 1.84 (95% CI, 1.31-2.56). Thus, the 'high
      normal blood pressure' is considered as a risk factor for hypertension in Korean
      middle-aged men, which suggests that the vigorous lifestyle modification for
      persons with 'high-normal blood pressure' is needed.

PMID- 12068136
TI  - Defective erythropoiesis in bone marrow is a mechanism of anemia in children with
      cancer.
AB  - Evaluation of the mechanism of anemia in cancer patients might help to select
      patients for the more efficient use of erythropoietin (EPO, a growth factor for
      erythroid precursor cells). For this, we investigated whether the production of
      EPO responds to anemia and the bone marrow responds to EPO appropriately, and
      whether chronic inflammation is inhibitory to erythropoiesis in anemic cancer
      children. Serum levels of EPO, soluble transferrin receptor (sTfR), tumor
      necrosis factor (TNF)-alpha, and erythrocyte sedimentation rate (ESR) in anemic
      cancer children were measured by enzyme-linked immunosorbent assay and then the
      correlation coefficients between those parameters and hemoglobin (Hb) were
      determined. Both in leukemia and in solid tumor patients, there were significant
      inverse correlations between Hb and EPO (leukemia: tau=-0.547, p<0.0001; solid
      tumor: tau=-0.591, p<0.0001), and between sTfR and EPO (leukemia: tau=-0.223,
      p<0.05; solid tumor: tau=-0.401, p<0.05). In contrast, sTfR showed a correlation
      with Hb in leukemia (tau=0.216, p<0.05) but not in solid tumor patients. sTfR was
      suppressed in 53% of anemic episodes of leukemia and 78% of those of solid tumor
      patients. Our results suggest that in cancer children, the EPO production is not
      defective and chronic inflammation is not inhibitory to erythropoiesis. Rather,
      the defective erythropoiesis itself is thought to be responsible for the anemia.

PMID- 12068137
TI  - Survival benefits of lung cancer patients undergoing laser and brachytherapy.
AB  - We aimed to compare the duration of survival among subjects receiving
      brachytherapy (BT) in combination with Nd:YAG laser therapy (LT), and those
      receiving LT or BT alone. The medical records of subjects who received
      endobronchial treatment for unresectable tracheobronchial malignancies between
      January 1997 and December 1999 in a single center were reviewed retrospectively.
      A total of 80 patients were evaluated. The overall symptomatic response rate
      after treatment was 86.5%. Median survival durations for the LT, BT, and combined
      therapy (CT) group were 111, 115, and 264 days, respectively. The survival
      duration was significantly longer in the CT group than in the BT group
      (p=0.0078), but the difference was not statistically significant between the CT
      and the LT group. The bronchoscopic finding of endobronchial polypoid lesion was
      associated with a longer survival time than extraluminal with compression type
      (p=0.0023) by univariate analysis. Other factors associated with the better
      prognosis included hemoglobin > or = 12.5 g/dL, serum albumin level > or = 37
      g/L, and BT dose > or = 15 Gy at 1 cm distance. Of these factors, specific
      bronchoscopic findings, serum albumin level, CT modality, and dose of BT retained
      statistical significance in multivariate analysis. In conclusion, combined LT and
      BT is associated with increased patient survival compared with BT alone. Combined
      therapy may improve survival time in selected patients with endobronchial
      malignancies.

PMID- 12068138
TI  - Epirubicin, cisplatin, and protracted venous infusion of 5-fluorouracil for
      advanced gastric carcinoma.
AB  - To evaluate the activity and safety of a combination chemotherapy with
      epirubicin, cisplatin, and a protracted venous infusion of 5-fluorouracil (ECF)
      in unresectable or metastatic gastric cancer, a phase II study was performed.
      Thirty-five chemotherapy-naive patients were given ECF. Epirubicin (50 mg/m(2)
      intravenous, i.v.) and cisplatin (60 mg/m(2) i.v.) were administered every three
      weeks during a continuous intravenous infusion of 5-fluorouracil (250 mg/m(2)
      /day) using infusion pump. One complete response and 19 partial responses
      (response rate=62%) were achieved. Eight patients remained stable, whereas in
      four patients the disease progressed. The median duration of response was 22
      weeks (95% confidence interval, 18-27 weeks). The median survival for all
      patients was 10 months (95% confidence interval, 6-14 months), with a 1-yr
      survival rate of 40%. A total of 184 cycles of chemotherapy were administered.
      Grade 3 or 4 emesis occurred in 3%, mucositis in 2%, anemia in 10%, and
      leukopenia in 3% of the cycles. Central venous catheter complications that
      required line removal occurred in 37% (n=13) of the patients. No patient died of
      toxicity. Overall, the ECF regimen showed high anti-tumor activity with a
      tolerable toxicity pattern.

PMID- 12068139
TI  - Fine needle aspiration cytology (FNAC) of gastrointestinal stromal tumor: an
      emphasis on diagnostic role of FNAC, cell block, and immunohistochemistry.
AB  - Recently the origin of gastrointestinal stromal tumors (GISTs) is thought be the
      interstitial cells of Cajal or primitive stem cells. This study was performed to
      evaluate the roles of fine needle aspiration cytology (FNAC), cell block
      preparation, and immunohistochemistry in the diagnosis of GISTs. Nine cases of
      GIST in which FNAC was performed were included in this study. Cytologically, the
      tumor cells characteristically occurred in closely packed cohesive tissue
      fragments with high cellular density often in bloody background. The tumor cells
      often formed fascicles with parallel, side-by-side arrangements of the nuclei.
      Histologically, GISTs were highly cellular spindle or epithelioid tumor with
      basophilic appearance. Immunohistochemically, GISTs were c-kit positive in all of
      nine cases, CD34 positive in seven, focally SMA positive in two, and S-100 and
      GFAP negative in all. Both histologic and cell block sections showed the same
      histologic and immunohistochemical features. Cytomorphologically GISTs show a
      broad morphologic spectrum but rarely a significant nuclear pleomorphism and the
      assessment of malignant potential is difficult based on cytology alone. However,
      in the appropriate clinical and radiologic setting, a confident diagnosis of
      primary or metastatic GIST can be established by FNAC, cell block, and
      immunohistochemistry.

PMID- 12068140
TI  - Telomere length changes in colorectal cancers and polyps.
AB  - Telomere shortening and telomerase activation occur frequently in cases of
      colorectal carcinoma. In this study, we correlated the clinicopathological
      parameters with the telomere length in colorectal carcinomas, colonic polyps, and
      normal colonic tissues. We also investigated whether the telomere length changes
      reflect the biologic behavior of tumors and different modes of tumor development.
      Telomere length was determined by terminal restriction fragment Southern blot
      analysis in 20 invasive colorectal carcinomas and normal mucosa from the same
      patients. We also examined 20 colonic polyps and associated normal mucosa.
      Telomere shortening was detected in 16/20 (80%), and telomere elongation in 2/20
      (10%) cases of colorectal carcinoma, and no changes in 2 subjects. In the colonic
      polyp patients, shortening was detected in 4/20 (20%), elongation in 6/20 (30%),
      and no change in 10/20 (50%). The frequency of telomere shortening was
      significantly different between colorectal carcinoma and polyp groups. Decreased
      telomere length was noted in 92.9% (13/14) of Dukes' C and 50% (3/6) of Dukes' B.
      The difference between these two sub-groups was statistically significant. This
      study suggests that the telomere length in colorectal carcinomas is decreased
      upon the development of malignancy. A significant difference in telomere length
      between polyps and invasive colorectal carcinomas may reflect a different
      biologic behavior of colorectal carcinomas.

PMID- 12068141
TI  - Association of MICA polymorphism with HLA-B51 and disease severity in Korean
      patients with Behcet's disease.
AB  - The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many
      ethnic group. However, it has not yet been clarified whether the HLA-B51 gene
      itself is the pathogenic gene related to BD or whether it is some other gene in
      linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC)
      polymorphism in transmembrane region of the MHC class I chain-related A (MICA)
      gene was identified. To investigate the association of MICA with BD, we studied
      the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in
      relation to the presence of HLA-B51 and clinical manifestations. The triplet
      repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing
      polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6
      allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were
      significantly increased in the Korean patients with BD. A strong linkage
      disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients
      with BD and control subjects. Stratification analysis showed that MICA*A6
      homozygosity was strongly associated with BD in the HLA-B51-negative population,
      and HLA-B51 was also associated with MICA*A6-negative population. In conclusion,
      MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD,
      and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the
      HLA-B5-negative

PMID- 12068142
TI  - The clinical significance of a pathergy reaction in patients with Behcet's
      disease.
AB  - This study was done to evaluate the frequency, intensity, and specificity of a
      positive pathergy reaction (PR) in Behcet's disease (BD) patients, to clarify an
      association between the PR and the clinical features or disease severity, and to
      assess whether patients with pustule formation at the venous puncture site
      (PFVPS) without positive PR could be regarded as a positive reaction. The PR was
      tested in 64 BD patients, 74 disease controls, and 20 healthy controls. Venous PR
      was performed in 8 BD patients with PFVPS. Follow-up PR was done in 14 patients
      with positive reaction during inactive phase. The PR was positive in 35.9% of BD
      patients, in 1 patient among disease controls, and in none of healthy controls.
      The pustule formation was observed in one BD patient. There was no statistical
      significance between positive PR and the clinical variables. The mean clinical
      activity score of BD patients with positive PR was similar to patients with
      negative reaction. Venous PR was positive in 7 patients. The follow-up PR was
      positive in 2 patients during inactive phase. Conclusively the positive PR
      appeared to be specific for BD, and was not associated with the clinical
      variables or disease severity, but was usually found during active phase in cases
      with positive reaction. The PFVPS in patients with negative PR might be
      considered to be positive.

PMID- 12068143
TI  - Role of IgG, IgA, and IgE antibodies in nasal polyp tissue: their relationships
      with eosinophilic infiltration and degranulation.
AB  - To confirm local production of IgE, and evaluate role of immunoglobulins on
      eosinophil activation in nasal polyp (NP) tissue, we measured IgG, IgA, secretory
      IgA(sIgA), total (tIgE) and specific IgE (sIgE) to Dermatophagoides
      pteronyssinus(DP) by ELISA in NP tissue homogenates from 51 subjects. They were
      classified according to skin reactivity to DP: group I, 15 highly atopic
      subjects; group II, 18 weakly atopic subjects; and group III, 18 non-atopic
      subjects. Eosinophil cationic protein (ECP) level was measured by CAP system.
      Highest level of DP-sIgE was noted in group I, followed by group II and III
      (p<0.05). Nine (60%) of group I and 4 (22%) of group II subjects had detectable
      level of DP-sIgE with no significant differences in IgA, sIgA, and IgG. All of NP
      tissue had eosinophilic infiltration with no significant difference in activated
      eosinophil count or ECP level among 3 groups. A significant correlation was noted
      between EG2+ cell count and tIgE (r=0.55, p<0.05), and DP-sIgE level (r=0.60,
      p<0.05). A significant correlation was also noted between ECP and IgG (r=0.51,
      p<0.05) and DP-sIgE level (r=0.47, p<0.05) with no significant correlation with
      IgA or sIgA. These results suggest that DP-sIgE was detectable in NP tissue from
      weakly atopic subjects as well as highly atopic subjects. IgG and sIgE may have
      potential roles in eosinophil degranulation in NP tissue.

PMID- 12068144
TI  - Expression patterns of cytokeratins in cholesteatomas: evidence of increased
      migration and proliferation.
AB  - Aural cholesteatoma is characterized by invading squamous epithelia with altered
      growth properties. Cytokeratin (CK) expression is affected in epidermal
      proliferative diseases and represents the alterations of keratinocyte
      proliferation, differentiation, and migration. In the present study, the
      intensity of CK immuno-expression was determined, using densitometry at various
      sites in experimental cholesteatoma in order to characterize changes of
      keratinocytes. With cholesteatoma formation, CK4, a marker for non-keratinizing
      epithelia, increased in the suprabasal layers of the annular external auditory
      canal (EAC) and at the pars tensa indicating an altered differentiation and
      migration of keratinocytes. CK5/6, a marker of keratinizing squamous epithelium,
      increased only at the pars tensa of the tympanic membrane, indicating basal
      keratinocyte hyperplasia. CK1/10 increased in the suprabasal layer at the annular
      EAC, and at the peripheral pars tensa, indicating increased terminal
      differentiation of keratinocytes. CK13/16, markers of differentiation and
      hyperproliferation, increased in suprabasal layer of the EAC, and at the
      peripheral pars tensa. However, it decreased in the basal layer of the EAC,
      indicating hyperproliferation and migration of keratinocytes. The findings of
      this study support the basal cell hyperplasia hypotheses for the pathogenesis of
      aural cholesteatoma, with regard to hyperproliferation, migration, and an altered
      differentiation of keratinocytes.

PMID- 12068145
TI  - The role of nitric oxide in ocular surface cells.
AB  - The role of nitric oxide (NO) in the ocular surface remains unknown. We
      investigated the conditions leading to an increase of NO generation in tear and
      the main sources of NO in ocular surface tissue. We evaluated the dual action
      (cell survival or cell death) of NO depending on its amount. We measured the
      concentration of nitrite plus nitrate in the tears of ocular surface diseases and
      examined the main source of nitric oxide synthase (NOS). When cultured human
      corneal fibroblast were treated with NO producing donor with or without serum,
      the viabilities of cells was studied. We found that the main sources of NO in
      ocular surface tissue were corneal epithelium, fibroblast, endothelium, and
      inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in
      experimentally induced inflammation. In the fibroblast culture system, the NO
      donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of
      corneal fibroblast cells caused by serum deprivation in a dose dependent manner
      up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study
      suggested that NO might act as a double-edged sword in ocular surface diseases
      depending on the degree of inflammation related with NO concentration.

PMID- 12068146
TI  - In vivo microdialysis measures of extracellular norepinephrine in the rat
      amygdala during sleep-wakefulness.
AB  - Norepinephrine (NE)-containing locus ceruleus (LC) has been known to participate
      in the regulation of the sleep-wake cycle according to the differential firing
      rate. The aim of this study was to know the change of extracellular NE level in
      the rat amygdala, which are reciprocally connected with LC, during sleep
      wakefulness. Extracellular NE levels in the rat amygdala were investigated during
      different stages of the sleep-waking cycle using in vivo microdialysis and
      polygraphic recording. Dialysates were collected every 5 min and correlated with
      the results of polygraphic recording. The content of NE was measured by high
      performance liquid chromatography with electrochemical detection. NE level was
      the highest in active waking (AW) and, when compared to AW, NE level was
      progressively lower in quiet waking (QW; 86%), quiet sleep (QS; 72%), and active
      sleep (AS or REM sleep; 61%). This result suggests that the rat amygdala also
      participates in the regulation of the sleep-wake cycle according to the
      differential NE release.

PMID- 12068147
TI  - Fetal axillary cystic hygroma detected by prenatal ultrasonography: a case
      report.
AB  - Fetal cystic hygroma is a rare developmental congenital anomaly of the lymphatic
      system, characterized by the formation of a multilocular, variable sized cystic
      mass. Most of cystic hygromas are found in the neck and other rare locations
      include axilla, mediastinum, and limbs. There are many papers about cystic
      hygroma colli, but there are only a few papers about fetal axillary cystic
      hygroma and no domestic papers. We present a case of fetal axillary cystic
      hygroma diagnosed antenatally followed by full-term delivery in a 30-yr-old
      woman. Operation was performed on the 8th day after birth and the mass was
      excised and confirmed as cystic hygroma.

PMID- 12068148
TI  - Two cases of disseminated mucormycosis in patients following allogeneic bone
      marrow transplantation.
AB  - We describe two cases of disseminated mucormycosis following allogeneic bone
      marrow transplantation (BMT). Both patients were suffering from chronic graft-ver
      sus-host disease (GVHD) and treated with prolonged administration of
      corticosteroid. In both cases, the initial symptoms were high fever and left
      flank pain. Involved organs were the spleen, right kidney and the right lung in
      one case, and the spleen and the brain in the other. The diagnosis was confirmed
      by pathology after splenectomy. One patient, in whom the immunosuppressants could
      be discontinued, was treated with prolonged conventional and liposomal
      amphotericin B and 5-fluorocytosine. The other, in whom the immunosuppressants
      could not be discontinued due to extensive GVHD, was unresponsive to amphotericin
      B, and eventually died from the fungal infection. Although mucormycosis,
      especially the disseminated form thereof is infrequent, it should be considered
      in high-risk patients because early diagnosis and timely therapy combining
      antifungal drug or surgery and reduction of immunosuppression appear to improve
      the prognosis.

PMID- 12068149
TI  - The multiple brain abscesses associated with congenital pulmonary arteriovenous
      malformations: a case report.
AB  - In this report, we describe a case of multiple brain abscesses associated with
      diffuse congenital pulmonary arteriovenous malformations (PAVM). Although the
      cases of brain abscesses associated with congenital PAVM are very rare, the brain
      abscess could be an initial clinical manifestation in asymptomatic PAVM as in the
      case presented in this report. PAVM may contribute to the development of a brain
      abscess by allowing easy bacterial access to systemic circulation through the
      right-to-left pulmonary vascular shunt, bypassing the filtering effect of the
      pulmonary capillaries. Hence, this association should be considered in cases with
      brain abscesses of undetermined etiologic factors.

PMID- 12068150
TI  - Endometrial stromal sarcoma of the sigmoid colon arising in endometriosis: a case
      report with a review of literatures.
AB  - Most of malignant tumors arising in ovarian and extraovarian endometriosis are
      carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in
      intestinal endometriosis are rarely described, but its clinicopathologic features
      have not been well characterized. Here we report a case of endometrial stromal
      sarcoma of the sigmoid colon arising in endometriosis with a review of six
      additional cases of endometrial stromal sarcoma arising in intestinal
      endometriosis found in English literatures. The patients ranged in age from 36 to
      64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some
      patients had a previous history of endometriosis. Most of the tumors arose in the
      rectosigmoid colon. The histologic features were the same as their uterine
      counterpart. No death of disease had been reported. This rare tumor should not be
      confused with gastrointestinal stromal tumor clinically and histologically.

PMID- 12068151
TI  - Hepatic resection of metastatic tumor from serous cystadenocarcinoma of the
      ovary.
AB  - Metastatic carcinomas are the largest group of malignant tumors of the liver. But
      parenchymal liver metastasis from cystic ovarian adenocarcinoma is very rare. We
      report a case in which the resection of metastatic liver neoplasm from ovarian
      serous cystadenocarcinoma was done 7 yr after initial treatment. A 48-yr-old
      oriental housewife complained of easy fatigability and right lower quadrant
      discomfort. The hepatic mass was detected by ultrasonographic examination. Serum
      albumin, bilirubin, and aspartate aminotransferase/alanine aminotransferase were
      normal. Alkaline phosphatase level was slightly increased at 146 IU/L. A tumor
      marker study showed alpha-fetoprotein 0.97 IU/mL, carcinoembryonic antigen 0.965
      ng/mL, cancer antigen 125 1,267 ng/mL and CA 19-9 106.1 ng/mL. The operation
      involved cholecystectomy and segmentectomy VI and VII of the liver. The patient
      recovered from the surgery without any complication. On the 10th postoperative
      day, the patient received a single-regimen chemotherapy with paclitaxel (Taxol,
      155 mg/m(2) BSA) and was discharged. She has been carefully followed-up without
      any evidence of recurrence after completion of the remaining 5 cycles of chemo
      therapy, at intervals of three weeks.

PMID- 12068152
TI  - Primary retroperitoneal synovial sarcoma: a case report.
AB  - A case of a 36-yr-old woman with retroperitoneal synovial sarcoma is described.
      Her presenting symptom was epigastric pain that radiating to the back. On
      radiologic study, bulky retropancreatic soft tissue mass was detected which
      showed cystic and solid components. At operation, complete resection of the tumor
      was not possible because of the adhesion to the vena cava and the liver. During
      the follow-up, extensive tumor recurrence and liver metastasis were revealed.
      Primary retroperitoneal synovial sarcoma is a very rare malignant tumor with high
      mortality and recurrence rates. Retroperitoneal synovial sarcoma usually appears
      as a nonspecific soft tissue mass that do not have specific imaging features
      differentiating it from other mesenchymal tumors. However general radiologic
      findings and anatomic location of the tumor may help the diagnosis. In addition,
      synovial sarcoma should be included in the differential diagnosis of
      retroperitoneal soft tissue mass detected in young adults.

PMID- 12068153
TI  - A case of calcium pyrophosphate dihydrate crystal deposition disease presenting
      as an acute polyarthritis.
AB  - We report a case of calcium pyrophosphate dihydrate crystal deposition disease
      (CPDD) presenting as an acute polyarthritis. A 66-yr-old woman was admitted with
      a 5-day history of fever and multiple joint pain including wrists, elbows,
      shoulders, knees, and ankles developed 5 days before admission. Her plain
      radiographs of wrists, elbows, shoulders, knees, and ankles showed
      chondrocalcinosis. The pubic symphysis, lumbar intervertebral discs, and both hip
      joints, which were asymptomatic, also had calcium deposits. The compensated
      polarized microscopic examination of the joint fluid, aspirated from the right
      knee revealed intracellular and extracellular weakly positive birefringent
      crystals, confirming the CPDD. This case showed that CPDD may manifest as an
      acute polyarthritis mimicking acute onset rheumatoid arthritis.

PMID- 12068154
TI  - Oligodendroglioma arising in a sacrococcygeal immature teratoma.
AB  - Tumors of neuroepithelial origin are extremely rare in teratoma and tend to be
      derived from glial or primitive neuroectodermal cells. We describe a case of 2-
      month-old baby girl with an oligodendroglioma arising in an immature teratoma of
      the sacrococcygeal region. Histologically, the tumor was identical in appearance
      to low grade oligodendroglioma within the adult brain. Because immature teratoma
      was grade II, the patient received adjuvant chemotherapy. The patient died of
      progression of the intra-abdominal tumor 6 months after surgical excision. The
      authors believe this to be the first presentation in the world literature.

PMID- 12068155
TI  - Leiomyoma in the posterior choroid: a case report.
AB  - Smooth muscle tumor of the uveal tract is rare, and mostly located in the cilio
      choroidal area. We report a unique case of posterior choroidal leiomyoma in a 27
      yr-old man. Ophthalmoscopic examination disclosed an 11 mm-sized mass on the
      fundus two-disc diameters apart from the optic disc. With a suspicion of
      amelanotic melanoma, the globe was enucleated. The mass occupied the whole
      thickness of choroidal stroma beneath the pigmented retinal epithelium and
      composed of spindle cells arranged in intersecting fascicles. Immunohistochemical
      studies demonstrated immunoreactivities of the tumor cells for smooth muscle
      actin, desmin, and vimentin. Ultrastructurally, numerous intracytoplasmic
      filaments with fusiform focal densities, scattered segmental external laminae,
      subplasmalemmal densities, and pinocytic vesicles were noted. The leiomyoma in
      this case had several unusual features in that it was confined to the posterior
      choroid with no relation to the ciliary body, occupied the whole stroma of the
      choroid instead of suprauveal location, and occurred in a young male. It is
      important to include choroidal leiomyoma in the differential diagnosis of
      choroidal tumors.

PMID- 12068156
TI  - Biexponential T2 relaxation time analysis of the brain: correlation with
      magnetization transfer ratio.
AB  - RATIONALE AND OBJECTIVES: To measure T2 relaxation times of normal white and gray
      matter using a novel CPMG sequence and investigate if any correlation exists
      between magnetization transfer ratio (MTR) and T2 relaxation-related parameters.
      MATERIALS AND METHODS: Seventeen normal volunteers participated on this study. A
      single-slice 32-echo sequence was used to calculate the T2 relaxation time of
      frontal and occipital white matter and cortical gray matter. T2 relaxation
      analysis included monoexponential and biexponential fitting whereas an F test was
      used to determine if biexponential fitting was statistically more accurate than
      monoexponential fitting. Short and long T2 constants were calculated as well as
      the signal fractions of each pool. MTR calculations were based on a three
      dimensional gradient echo (3D FFE) proton density weighted sequence with and
      without an on-resonance composite prepulse. MTR and T2 relaxation times were
      calculated and linear regression analysis was applied. RESULTS: Biexponential
      fitting was more accurate comparing with monoexponential fitting in all WM and GM
      regions (F > 2.47, P < 0.01). Mean values of short T2 constant for frontal white
      matter (fWM), occipital white matter (oWM) and gray matter (GM) were 8.10, 9.36,
      and 22.23 milliseconds, respectively, whereas the mean values of long T2 constant
      were 85.1, 93.02, and 118.72 milliseconds, respectively. Mean restricted water
      percentages (RWP)-corresponding to the signal fraction of the protons with short
      T2-for the fWM, oWM, and GM were 22.01%, 23.36%, and 18.7%. Mean free water
      percentages (FWP)-corresponding to the signal fraction of the protons with long
      T2-for the fWM, oWM and GM were 77.99%, 76.64%, and 81.3%. Mean MTR values for
      fWM, oWM and GM were 68.4%, 68.2%, and 61.3%, respectively. No significant
      correlation was found in fWM and oWM between MTR and RWP, short and long T2
      components while a moderate correlation existed in GM between MTR and RWP (r =
      0.57; P = 0.02), MTR and short T2 component (r = -0.69; P = 0.004) and MTR and
      long T2 component (r = -0.62; P = 0.012). CONCLUSIONS: Two proton pools with
      different T2 decay characteristics can be separated in normal gray and white
      matter when using a multiecho sequence with short echo spacing. MTR and T2
      relaxation times were significantly correlated in gray matter and the combination
      of both types of measurements may be helpful in studying myelin related
      disorders.

PMID- 12068157
TI  - Effects of two dimeric iodinated contrast media on renal medullary blood
      perfusion and oxygenation in dogs.
AB  - RATIONALE AND OBJECTIVES: To compare the effects of two iodinated contrast media,
      iodixanol and ioxaglate, on outer medullary blood flow (MBF) and oxygen tension
      (MPO(2)) in the dog kidney. METHODS: Iodixanol and ioxaglate were injected
      selectively into the renal artery (320 mgI/kg) of anesthetized Beagle dogs. MBF
      and MPO(2) were measured with a laser-Doppler probe and an oxygen-sensing
      microelectrode implanted in the outer medulla. Urine samples were collected for
      viscosity and osmolality measurements. RESULTS: Both contrast media produced a
      moderate decrease in MBF and MPO(2). The hypoperfusion and hypoxia lasted
      significantly longer with iodixanol than with ioxaglate. Theophylline, an
      adenosine receptor antagonist, partially prevented iodixanol-induced hypoxia.
      Urine viscosity was dramatically increased by iodixanol but not by ioxaglate.
      Urine osmolality did not differ significantly between groups. CONCLUSION:
      Iodixanol produced a more sustained medullary hypoxia than ioxaglate when
      injected selectively into the dog renal artery. This may lead to hypoxic cellular
      damage and subsequent impairment of kidney functions.

PMID- 12068158
TI  - Ultrasound score is more predictive than serum creatinine in assessment of
      cellular rejection in cynomolgus monkey renal allografts.
AB  - RATIONALE AND OBJECTIVES: To investigate whether ultrasound (US), in particular
      the use of an ultrasound scoring system, can provide more diagnostic information
      than clinical parameters, such as serum creatinine, for the diagnosis and
      determination of the degree of cellular rejection in renal allografts in the
      cynomolgus monkey (Macaca fascicularis). METHODS: Sixty-eight cynomolgus monkeys
      with life-supporting renal allografts were examined with a 7.5MHz linear
      ultrasound transducer. One-hundred fifty two-dimensional, spectral, and power
      Doppler examinations were performed and four ultrasound parameters, percentage
      increase in graft volume, cortical thickness, resistive index (RI) of the renal
      arcuate artery, and power Doppler (PD) scores were recorded from serial
      examinations. An ultrasound score was assigned to each graft based on the number
      of those parameters that were abnormal; a score of 1 indicated that all four were
      normal, and a score of 5 that all four were abnormal. Each parameter and the
      combined score were compared with serum creatinine values and histology and
      evaluated statistically using Spearman rank correlation. RESULTS: In animals with
      dysfunctioning allografts (serum creatinine elevations >200 micromol/L), Spearman
      rank correlation showed a significant correlation between the US score and the
      histology score: between 200 and 500 micromol/L, r = 0.309, P = 0.046, n = 31 and
      if > 500 micromol/L, r = 0.486, P = 0.005, n = 30. In those same animals, no
      correlation could be shown between serum creatinine values and the US score or
      between the serum creatinine values and the histologic diagnosis. In contrast to
      the US score, single ultrasound parameters were not found to correlate to
      histologic findings. CONCLUSION: The application of ultrasound imaging in
      nonhuman primate renal transplant models provides valuable information concerning
      the presence and severity of cellular rejection in cases of graft dysfunction and
      the US score has a better predictive value of histology than serum creatinine
      values alone.

PMID- 12068159
TI  - Histopathologic correlation of high-resolution magnetic resonance imaging of
      human cervical tissue samples at 3 tesla: validation of a technique.
AB  - RATIONALE AND OBJECTIVES: High-resolution magnetic resonance (HR-MR) images of
      human cervical tissue samples were correlated with low magnification histology to
      investigate the MR presentation of normal and pathologic anatomic structures in
      cervical tissue samples at 3T. METHODS: Tissue samples were obtained from five
      large loop excision of the transformation zone (LLETZ) cone biopsies and one
      surgical specimen. HR-MR images (3D-Spin Echo sequence: TR/TE: 1500/60
      milliseconds, voxel size of 117 x 208 x 234 microm) and low magnification (5x)
      histology sections were acquired in the same anatomical planes and correlated.
      RESULTS: In vitro HR-MR imaging of cervical tissue samples correlated well with
      low magnification microscopic histology, demonstrating normal anatomy (epithelium
      and its mucus layer, connective tissue of the stroma, glands, blood vessels). In
      vitro HR-MR imaging adds information about tumor content and margins.
      CONCLUSIONS: High resolution MR imaging of cervical tissue samples assists in the
      identification of both normal structures and pathologic changes.

PMID- 12068160
TI  - A direct comparison of noninvasive coronary angiography by electron beam
      tomography and navigator-echo-based magnetic resonance imaging for the detection
      of restenosis following coronary angioplasty.
AB  - RATIONALE AND OBJECTIVES: To compare electron beam tomography (EBT) with MR
      imaging (MRI) for detection of restenosis after coronary angioplasty (PTCA).
      METHODS: One hundred eighteen patients after PTCA were investigated. By EBT, 50
      axial images were acquired (3-mm slice thickness, 120-160 mL radiographic
      contrast agent). MRI was performed using respiratory-gated sequences (24-48 cross
      sections, 2-mm slice thickness, 20 mL Gd-DTPA). EBT and MRI images were evaluated
      concerning high-grade post-PTCA restenosis (> or = 70%) and validated against
      coronary angiography. RESULTS: In EBT, 28 patients and in MRI, 31 patients were
      not evaluable. In the remaining patients, sensitivity for restenosis detection
      was 90% in EBT (17/19) and 73% in MRI (11/15; P = 0.370). In EBT, specificity was
      significantly higher (66% vs. 49%, P = 0.043). Overall accuracy was 71% for EBT
      and 53% for MRI (P = 0.014). CONCLUSIONS: For the detection of high-grade
      restenosis after PTCA, EBT demonstrated significantly higher accuracy than MRI.

PMID- 12068161
TI  - Local tissue toxicity in response to extravascular extravasation of magnetic
      resonance contrast media.
AB  - RATIONALE AND OBJECTIVES: The relative toxicities of the gadolinium chelates
      currently available in the United States were compared when extravasated in soft
      tissue. The increasing use of these contrast agents in higher volumes and at
      faster injection rates, often with a power injector, was a principal motivation
      for this research. METHODS: Gadopentetate dimeglumine (Magnevist), gadoteridol
      (ProHance), gadodiamide (Omniscan), and gadoversetamide (Optimark) were evaluated
      at standard concentration and compared with a control (physiologic saline) and
      the conventional ionic radiographic contrast medium meglumine diatrizoate
      (Renografin 60). Each mouse received a subcutaneous injection in the hindlimb of
      0.3 mL of contrast or saline. There were 6 experimental groups, with 15 animals
      in each group. The individual performing the injection was blinded to the
      identity of the contrast agent used in each mouse. After 48 hours, the mice were
      killed and tissue samples obtained for histopathology. A veterinary pathologist,
      also blinded to the agent injected, graded the degree of damage seen on
      microscopic examination. RESULTS: Of the four MR contrast agents, gadopentetate
      dimeglumine caused the greatest tissue damage, and gadoteridol and gadodiamide
      the two lowest osmolar agents-the least. The difference was statistically
      significant in terms of both inflammation (P = 0.0008 for gadoteridol, and P =
      0.006 for gadodiamide) and necrosis (P = 0.0067 for gadoteridol, and P = 0.031
      for gadodiamide), when these agents were compared with gadopentetate dimeglumine.
      In regard to the control experiments, for all three variables (necrosis, edema,
      and inflammation), there was no statistically significant difference between the
      results with gadoteridol or gadodiamide and those with saline. In terms of both
      edema and inflammation, the effect of gadopentetate dimeglumine, although less,
      could not be differentiated with any statistical significance from that of
      meglumine diatrizoate. Gadoversetamide, which has an osmolality between the ionic
      agent (gadopentetate dimeglumine) and the other two nonionic agents, caused a
      reaction that could not be differentiated from that seen with gadopentetate
      dimeglumine for both necrosis and edema. Only in the scoring of inflammation was
      the effect less using gadoversetamide compared to gadopentetate dimeglumine with
      any statistical significance (P = 0.021). CONCLUSIONS: The risk of tissue damage
      due to extravasation is not widely appreciated for the gadolinium chelates. Care
      should be exercised during contrast injection, to avoid inadvertent extravasation
      and its deleterious consequences, in particular with the two higher osmolar
      agents (gadopentetate dimeglumine and gadoversetamide).

PMID- 12068162
TI  - Paclitaxel inhibits proliferation of cell lines responsible for metal stent
      obstruction: possible topical application in malignant bile duct obstructions.
AB  - RATIONALE AND OBJECTIVES: To evaluate a dose dependent inhibitory effect of
      paclitaxel to assess a possible local application for biliary tract malignancies
      in conjunction with stent placement. METHODS: Cell cultures of the three
      different cell types (human epithelial gallbladder cells [HEGC], human
      fibroblasts [HF; PA 314 wt] and pancreatic carcinoma cells [PC; P181]) were
      incubated for 20 minutes at 37 degrees C with increasing doses of paclitaxel (1.0
      x 10(-4) - 1.0 x 10(2) micromol). Half of the cultures were then incubated
      without paclitaxel, the other half with paclitaxel for 20 minutes, 24 hours, or
      72 hours. Cell proliferation was detected by photometric measurements of
      mitochondrial dehydrogenase activity (MTT assay). RESULTS: Incubation of cell
      cultures with paclitaxel resulted in a dose dependent and cell specific
      inhibition of cell proliferation. Concentrations of 1.0 x 10(-4) (and higher)
      paclitaxel for 20 minutes resulted in a inhibition of cell proliferation of HEGC
      (28%), PA (26%), and HF (17%). A prolonged paclitaxel incubation (up to 72 hours)
      resulted in an inhibitory effect on cell proliferation of HEGC (40%), PA (45%),
      and HF (39%). Cytotoxic effects, manifested by development of vacuoles and damage
      of cell integrity were seen at concentrations above 1.0 x 10(1) for both the
      short and long term incubation. CONCLUSIONS: Paclitaxel incubation resulted in a
      dose dependent inhibition of cell proliferation of human epithelial gallbladder
      cells, human fibroblasts and pancreatic carcinoma cells. This inhibitory effect
      of paclitaxel on the cell lines could serve as the basis to develop drug coated
      or drug eluting stents for malignant biliary strictures.

PMID- 12068163
TI  - Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques:
      postmortem analysis of accuracy, inter-observer agreement, and pitfalls.
AB  - INTRODUCTION: Contrast-enhanced magnetic resonance (MR) imaging using ultra small
      superparamagnetic iron oxide (USPIO) particles is a new noninvasive modality for
      imaging inflammatory atherosclerotic plaques. We determined the accuracy,
      interobserver agreement, and potential sources of error of this technique by
      means of postmortem MR imaging of aortic preparations. MATERIAL AND METHODS:
      Anesthetized atherosclerotic Watanabe heritable hyperlipidemic (WHHL) rabbits
      were studied after administration of different dosages of intravenous USPIO (DDM
      43/34, IDF Berlin, Germany) and different postcontrast time intervals. A (n = 5)
      received 0 micromol Fe/kg. B (n = 5) received 50 micromol Fe/kg, 8-hour
      postcontrast interval. C (n = 5) received 50 micromol, 24 hours. D received 200
      micromol, 48 hours. The aortas were removed and 3-mm segments prepared for
      postmortem examination by MR imaging using a T2-weighted gradient-echo sequence
      (TR/TE/FA; 41 milliseconds/11 milliseconds/15 degrees ), radiography
      (mammography), and histology (iron staining). USPIO accumulation was defined as
      the presence of 20 iron-positive cells per microscopic view (x100 magnification).
      Two independent readers analyzed the MR images and rated their confidence level
      for a positive MRI finding, defined as a focal signal loss, on a 5-point scale.
      The results were evaluated by receiver-operator characteristic (ROC) analysis.
      RESULTS: Of a total of 621 vessel segments technically acceptable for evaluation,
      534 were histologically negative and 87 positive. Accuracy, expressed as the area
      under the ROC curve, was 0.85 for reader 1 and 0.88 for reader 2. Interobserver
      agreement was 0.67. False-positive findings were established by at least one
      reader for 121 of the 621 segments, false-negative findings for only 15 segments.
      Calcifications and mural thrombi were identified as potential sources of error of
      the method. CONCLUSION: Postmortem USPIO-enhanced MR imaging of atherosclerotic
      plaques showed a high accuracy and good interobserver agreement in the animal
      model used here. Further optimization of the method should aim at reducing the
      rather high percentage of false-positive results.

PMID- 12068164
TI  - Clonality analysis in synchronous or metachronous tumors of the female genital
      tract.

PMID- 12068166
TI  - Immunohistochemical staining in the distinction between primary endometrial and
      endocervical adenocarcinomas: another viewpoint.
AB  - Several studies have reported on the use of antibodies to monoclonal
      carcinoembryonic antigen (CEA) and vimentin (VIM) to distinguish between
      adenocarcinomas of endometrial (EM) and endocervical (EC) origin, with variably
      enthusiastic results. It is still unclear whether site of origin or pathway of
      differentiation (endometrioid [em] versus mucinous [m]) is more important in
      predicting immunohistochemical differences. In the present study, paraffin blocks
      from adenocarcinomas of known origin were retrieved and immunostained with
      monoclonal antibodies to VIM and CEA, as well as cytokeratins (CK) 4, 18, and 20,
      estrogen receptor (ER), and progesterone receptor (PR). Positivity was scored on
      a scale from 0 to 12, with emphasis on the pattern of differentiation (tumors
      with mixed patterns received separate scores for the em and m foci). Mean CEA
      scores for emEM (n = 27), mEM (17), mEC (10), and emEC (6) were 0.4, 0.9, 5.1,
      and 1.2, respectively. VIM scores were 6.9, 1.3, 0, 4.4; ER, 5.7, 4.2, 0, 1.6;
      PR, 7.6, 2.8, 0.1, 6.0; CK4, 9.2, 4.4, 8.5, 10.6; CK18, 6.4, 3.4, 5.5, 8.4; CK20,
      0.7, 0, 0.5, 0.4. Both site and differentiation influenced these results, with
      the latter more important for VIM and PR, the former for ER, both for CEA (only
      mEC was frequently strongly positive), and neither for the CKs studied. No one
      stain or combination reliably distinguished endometrial from endocervical origin.
      The only immunostaining pattern that might identify a site of origin with more
      accuracy than hematoxylin & eosin evaluation alone is the combination of high VIM
      and ER scores in an endometrioid carcinoma, suggesting with about 95% accuracy in
      this series an endometrial origin of the tumor.

PMID- 12068167
TI  - Trichofolliculoma of the vulva associated with vulvar intraepithelial neoplasia:
      report of three cases and review of the literature.
AB  - Trichofolliculoma is an uncommon, benign cutaneous adnexal neoplasm most commonly
      occurring on the head and neck. Trichofolliculoma of the vulva has not been
      previously reported. The juxtaposition of a trichofolliculoma in an excisional
      biopsy specimen performed for vulvar intraepithelial neoplasia (VIN III) created
      a diagnostic dilemma and prompted a review of our files from 1989 to 2000 for
      additional cases. A search for benign hair follicle tumors of the vulva
      identified two additional trichofolliculomas. All three vulvar trichofolliculomas
      were associated with VIN III. During this same period, 628 cases of vulvar
      intraepithelial neoplasia II and III were identified. The appearance of
      trichofolliculoma at this previously unreported site may present diagnostic
      difficulty.

PMID- 12068168
TI  - Midluteal endometrial biopsy and alphavbeta3 integrin expression in the
      evaluation of the endometrium in infertility: implications for fecundity.
AB  - It has been recently proposed that the immunohistochemical evaluation of
      alphavbeta3 integrin in combination with histologic dating in midluteal
      endometrial biopsy specimens should be performed to evaluate the endometrial
      receptivity in the infertile patient. However, no studies have attempted to
      correlate these findings with subsequent fecundity. In 100 consecutive infertile
      patients (mean age 31.9+/-3.4 years) undergoing a routine work-up, two
      endometrial biopsies were performed during a single menstrual cycle: a midluteal
      biopsy on postovulatory days 6 to 8 and another biopsy 4 days later. Histological
      dating and immunohistochemical evaluation of alphavbeta3 integrin expression were
      done in all endometrial biopsy specimens. All patients were followed without
      treatment during 18 to 24 months (mean 23.5+/-1.4, range 18 to 24). Twenty-five
      midluteal biopsies showed out-of-phase endometria, whereas all but one late
      luteal biopsy specimens were in-phase. Glandular alphavbeta3 integrin expression
      was observed in 50% of midluteal specimens with this expression being
      significantly more frequent among in-phase (63%) than among out-of-phase (12%)
      specimens (p<0.001). However, all late-luteal specimens strongly expressed this
      integrin. Thirty-eight women became spontaneously pregnant during the follow-up
      period, 32 ended in a live birth and 6 in first trimester spontaneous abortion.
      The Cox regression method showed no differences between the hazard of pregnancy
      when the alphavbeta3 integrin-positive and -negative groups were compared (odds
      ratio 1.25; 95% confidence interval [CI] 0.66-2.36; p=0.49) or when patients with
      in-phase endometria were compared with those with delayed endometrial maturation
      (odds ratio 1.12; 95% CI 0.53-2.37; p=0.76). In conclusion, neither midluteal
      histological evaluation nor alphavbeta3 integrin expression in mid- or late
      luteal endometrial biopsy specimens correlated with outcome for subsequently
      untreated infertile women.

PMID- 12068169
TI  - Adenocarcinomas arising from uterine adenomyosis: a report of four cases.
AB  - Adenocarcinomas arising from adenomyosis uteri are rare. This study reports four
      such cases and characterizes them clinically and microscopically. In all four
      patients, the endometrial cytology was negative, and MR imaging and ultrasound
      sonography did not detect the tumors preoperatively. The histological subtypes of
      the four tumors were endometrioid (one grade 1, one grade 3), serous, and clear
      cell. In three cases, the adenocarcinomas were present exclusively in the
      myometrium, and a transition between the carcinomas and the adenomyotic glands
      was observed in all cases. The eutopic endometrium was normal except in one case
      in which there was a small focus of invasive carcinoma. In two of four cases,
      pelvic or paraaortic lymph node metastases were present. In the carcinomas, ER
      immunoreactivity was not found in any tumor and PR positivity was found in only
      one tumor. In contrast, p53 immunopositivity was found in three of four
      carcinomas. Adenocarcinomas arising from adenomyosis are difficult to diagnose
      preoperatively, and their aggressive behavior in some cases seems to be related
      to the histological subtype.

PMID- 12068170
TI  - Loss of gamma-Catenin expression in squamous differentiation in endometrial
      carcinomas.
AB  - Squamous differentiation occurs in 25 to 50% of endometrial endometrioid
      adenocarcinomas. In this study, we analyzed the immunohistochemical expression
      and localization of beta- and gamma-catenin, molecular changes in the beta
      catenin gene, and the subcellular localization of the desmosomal component
      protein, desmoplakin, by laser scanning microscopy in 35 endometrial carcinomas
      with squamous differentiation. In the glandular component, beta-catenin showed
      nuclear localization in 10 of 35 (28.5%) samples, whereas in the squamous
      component, nuclear localization was found in 15 of 35 (42.9%). Of the 15 samples
      that showed nuclear localization of beta-catenin in the squamous component, seven
      samples (46.7%) did not express gamma-catenin. The phenomenon was not correlated
      with mutation in exon 3 region of beta-catenin gene. Furthermore, in these
      samples, there was diffuse cytoplasmic staining for desmoplakin. These
      observations have not been reported in other tumors. Our results suggest that
      unique molecular events, i.e., stimulation of beta-catenin and suppression of
      gamma-catenin expression, occur within endometrial carcinomas with squamous
      differentiation.

PMID- 12068171
TI  - Growth-associated gene expression profiles by microarray analysis of trophoblast
      of molar pregnancies and normal villi.
AB  - We used microarray analysis to investigate expression profiles of 589 known genes
      committed to cell growth control to characterize regulatory circuitry for cell
      proliferation in complete moles (CMs). CMs are characterized by hyperplastic
      trophoblast and have a high propensity to give rise to choriocarcinoma.
      Characteristic alterations in gene expression profiles were observed when
      compared with normal villi. Fifty-seven genes were significantly up-regulated in
      CMs and involved the Ras-Map kinase 3, Jak-STAT5, and Wnt signal pathways,
      implicating growth factor or cytokine-mediated signal pathways in the
      trophoblastic hyperplasia of CMs. Several genes associated with anti-apoptosis,
      cell structuring, and/or cell attachment were also up-regulated in CMs. In
      contrast, relatively fewer genes were down-regulated and these involved IGFBPs,
      versican, interleukin-1, tumor necrosis factor receptor, CD44, and RAD52. Genes
      identified in this study may elucidate regulation mechanisms of trophoblastic
      proliferation and mechanisms causing a pathological phenotype in CMs.

PMID- 12068172
TI  - Prostatic tissue in mature cystic teratomas of the ovary: a report of four cases,
      including one with features of prostatic adenocarcinoma, and cytogenetic studies.
AB  - Four cases of mature cystic teratoma that contained prostatic tissue are
      reported. The ovarian tumors occurred in patients from 17 to 38 (mean 31) years
      of age and had no unusual clinical or gross aspects. The microscopic findings for
      the most part were typical of a mature cystic teratoma, but they also contained
      foci of prostatic tissue that ranged from 0.2 to 1.9 cm in greatest dimension. In
      these areas there was a lobular arrangement of medium-sized acini lined by
      cuboidal to columnar cells with pale cytoplasm and round nuclei with
      inconspicuous nucleoli except focally in one case as noted below. Basal cells
      were seen focally. The prostatic acini lay in a paucicellular fibromuscular
      stroma. In two cases thick layers of disorganized smooth muscle covered by
      transitional-like pseudostratified epithelium, resulting in an appearance
      resembling fetal bladder wall, were present next to the prostatic glands. One
      tumor also contained prostatic-type acini, which haphazardly infiltrated the
      stroma over an area approximately 5 mm in maximal dimension. The acini, a few of
      which contained intraluminal flocculent eosinophilic material, were lined by
      cells with eosinophilic to amphophilic focally granular cytoplasm and had nuclei
      that were enlarged compared with the benign-appearing, prostatic-type acini in
      the four cases and had focally prominent nucleoli. Basal cells were not
      identified in these infiltrating glands. Grading this focus according to the
      approach in the prostate, the morphology was that of a Gleason grade 3 of 5
      adenocarcinoma. Immunohistochemical stains of the putative prostatic epithelial
      cells confirmed their nature by showing immunoreactivity for prostatic-specific
      antigen in the lining epithelial cells in all four cases and for prostatic
      specific acid phosphatase in the one case tested. The high molecular cytokeratin
      stain, 34betaE12, highlighted basal cells to a variable extent in the three cases
      containing only benign prostatic tissue. Material was not available to
      immunostain for basal cells in the case with carcinoma. Cytogenetic studies were
      performed in two cases and showed that the great majority of the nuclei of the
      nonprostatic and prostatic tissue had an XX karyotype but from 3% to 5% of the
      nuclei displayed trisomy for the X chromosome. A small number of cases of
      prostatic tissue in ovarian teratomas have previously been documented but none
      had morphologic features of carcinoma.

PMID- 12068173
TI  - Malignant mullerian mixed tumor arising from ovarian serous carcinoma: a
      clinicopathologic and molecular study of two cases.
AB  - The clinical, histologic, and molecular pathologic features of two cases of
      malignant mullerian mixed tumor (MMMT) arising from ovarian papillary serous
      carcinoma are presented. Identical p53 mutations were detected in the primary
      ovarian carcinoma and the subsequent MMMT in each case.

PMID- 12068174
TI  - Gross deciduosis peritonei obstructing labor: a case report and review of the
      literature.
AB  - Gross deciduosis peritonei is a rare lesion characterized by the presence of
      grossly visible peritoneal decidual tissue in pregnant women; we present the
      clinicopathologic features of one such case. A 24-year-old, G4P1A2, Hispanic
      female underwent cesarean section at 39 weeks' gestation for dystocia related to
      pelvic masses. Multiple, light tan peritoneal masses involved the cul-de-sac,
      both ovaries, pelvic wall, omentum, and the large and small bowel. The
      intraoperative appearance suggested peritoneal carcinomatosis. A right ovarian
      mass was excised and biopsies were obtained from other sites. Microscopic
      examination showed the typical features of decidua in all of the lesions. Two
      weeks postoperatively, the patient was admitted with nausea and vomiting
      suggestive of a small bowel obstruction, which resolved after 2 days of medical
      treatment. After a postpartum visit at 5 weeks, the patient was lost to follow
      up.

PMID- 12068175
TI  - ACTH-secreting islet cell tumor of the pancreas presenting as bilateral ovarian
      tumors and Cushing's syndrome.
AB  - A 41-year-old woman presented with hirsutism, a pelvic mass, and Cushing's
      syndrome. Imaging studies revealed bilateral ovarian masses and a solid and
      cystic mass within the pancreas. Partial pancreatectomy, bilateral oophorectomy,
      and excision of several peritoneal tumor nodules were performed. Pathological
      examination revealed a neuroendocrine islet cell tumor of the pancreas with
      bilateral ovarian metastases. The tumor was immunoreactive for ACTH,
      chromogranin, neuron-specific enolase, and keratin. The patient received
      postoperative chemotherapy and has been disease-free for 6 years. To our
      knowledge, this is the first reported case of an ACTH-secreting pancreatic
      neuroendocrine tumor presenting as bilateral ovarian metastases.

PMID- 12068176
TI  - Endometrial endometrioid adenocarcinoma in a premenopausal woman presenting with
      metastasis to bone: a case report and review of the literature.
AB  - We describe the clinicopathologic and immunohistochemical features and
      microsatellite instability analysis of a rare case of endometrial endometrioid
      adenocarcinoma presenting as a metastasis to the ischium in a 39-year-old
      premenopausal woman. The patient was treated with a total abdominal hysterectomy,
      bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic
      lymphadenectomy. One month later, she underwent an ischial resection followed by
      radiotherapy. After a follow-up of 3 years, the patient shows no evidence of
      disease.

PMID- 12068177
TI  - Endometrioid adenocarcinoma arising from colonic endometriosis mimicking primary
      colonic carcinoma.
AB  - The clinicopathologic features of a case of endometrioid adenocarcinoma arising
      from colonic endometriosis that clinically and histologically mimicked a primary
      colonic carcinoma are reported. The differential diagnostic features of the tumor
      leading to the correct diagnosis included associated endometriosis, a minor
      mucosal component, focal squamous differentiation, absence of dirty necrosis, low
      nuclear grade, absence of a colonic adenoma, and a CK7+/CK20-/CEA-
      immunophenotype.

PMID- 12068178
TI  - Placentas, peccaries, and pathologists: reminiscences of Kurt Benirschke on his
      career: an interview with Rebecca N. Baergen.

PMID- 12068180
TI  - Adenomatoid tumors of the uterus.

PMID- 12068181
TI  - Florid vascular proliferation in grade 0 glial implants from ovarian immature
      teratoma.

PMID- 12068182
TI  - Distinction between endometrial and endocervical adenocarcinoma.

PMID- 12068184
TI  - Is ileoanal pouch function stable with time? Results of a prospective audit.
AB  - PURPOSE: Good continence is reported after ileal pouch-anal reconstruction, but
      little is known about long-term durability. Our aim was to prospectively evaluate
      long-term function in these patients. METHODS: Surveys were sent to 235 patients
      who had returned similar surveys in 1992; paired data were then compared with
      contingency tables. RESULTS: A total of 154 patients (66 percent) returned
      surveys. Mean age was 47 (range, 25-72) years. Median follow-up was 12 (range, 8
      19) years. Sixty-eight patients (44 percent) were female. There were 5 deaths,
      and 11 patients had pouches removed or were given a defunctioning ileostomy.
      Bowel movement frequency did not change from 1992 to 2000 (24-hour frequency = 7
      in 1992 vs. 7.1 in 2000; night frequency = 2 vs. 1.4; P = NS). Compared with 1992
      data, major day incontinence was worse in 18 percent of patients, improved in 1
      percent, and unchanged in 81 percent. Minor day incontinence was worse in 32
      percent, improved in 9 percent, and unchanged in 59 percent. Major nighttime
      incontinence was worse in 22 percent, improved in 6 percent, and unchanged in 72
      percent of patients, whereas minor night incontinence was worse in 24 percent,
      improved in 22 percent, and unchanged in 54 percent. Change in continence was
      unrelated to gender, age, or age at operation but was related to duration of
      follow-up. Twenty-seven percent of patients 12 or more years after surgery
      reported worsened major daytime incontinence vs. 9 percent of patients who were
      <12 years after surgery (P < 0.05); 33 percent reported more major night-time
      incontinence (vs. 10 percent; P < 0.05). Minor incontinence also worsened after
      12 years. Minor daytime incontinence was seen in 48 percent of patients followed
      up > 12 years vs. 16 percent of those followed up <12 years (P < 0.05); minor
      nighttime incontinence was 28 vs. 19 percent, respectively. CONCLUSION: Most
      patients have stable pouch function over time. However, a small number improve
      and a larger number suffer measurable deterioration, particularly 12 or more
      years after surgery.

PMID- 12068185
TI  - Restorative and nonrestorative surgery for low rectal cancer after high-dose
      radiation: long-term oncologic and functional results.
AB  - PURPOSE: This prospective, nonrandomized study evaluates, with a seven-year
      median follow-up, the morbidity and the functional and oncologic results of
      conservative surgery after high-dose radiation for cancer of the lower third of
      the rectum of patients who would otherwise have undergone abdominoperineal
      resection. METHODS: Between June 1990 and June 1996, 43 patients with distal
      rectal adenocarcinoma were treated by preoperative radiotherapy (40 + 20 Gy
      delivered with three fields) and curative surgery. The mean distance from the
      anal verge was 50 (range, 25-60) mm, and none of the tumors was fixed (15 percent
      T2N0, 53 percent T3N0, 32 percent T3N1). RESULTS: Postoperative mortality (2
      percent) and morbidity (35 percent) were not increased by high-dose preoperative
      radiation. Conservative surgery was done in 30 patients (70 percent: 26 coloanal
      anastomoses and 4 low stapled anastomoses). After conservative surgery, long-term
      functional results showed 30 percent complete continence and 20 percent serious
      incontinence. Four patients had local recurrence as first development (13
      percent). The seven-year overall survival rate was 53 percent, 62 percent after
      conservative surgery and 31 percent after abdominoperineal resection. The
      univariate analysis underscores the tumor response impact on long-term survival
      (pT<3 = 81 percent; pT3 = 35 percent; P = 0.0008). CONCLUSIONS: These long-term
      results confirm the feasibility of conservative surgery for low rectal carcinoma
      after high-dose radiation. A prospective multicentric trial began in France in
      June 1996 to evaluate the reproducibility of these results.

PMID- 12068186
TI  - Letter to the Editor.

PMID- 12068187
TI  - Septic complications and prognosis after surgery for rectal cancer.
AB  - PURPOSE: The influence of septic complications on long-term prognosis after
      surgery for rectal cancer is controversial. This study was performed to
      investigate whether an abdominal or perineal septic complication was associated
      with rectal cancer recurrence. METHODS: A total of 228 patients who had undergone
      curative resection for rectal cancer from 1973 to 1992 were reviewed. The
      patients were divided into groups of those who developed either an intra
      abdominal abscess or a perineal infection after surgery (infection group) and
      those who did not (noninfection group). RESULTS: There was no clear difference in
      the overall incidence of tumor recurrence between the infection group (19/53, 36
      percent) and the noninfection group (46/175, 26 percent; P = 0.25). However, the
      incidence of local recurrence was higher in the infection group (12/53, 23
      percent) than in the noninfection group (16/175, 9 percent; P = 0.02). This
      increased risk was restricted to patients with a perineal infection (10/30, 33
      percent; P = 0.003 vs. the noninfection group), whereas patients with an
      abdominal infection (3/24, 13 percent) did not differ from the noninfection
      group. CONCLUSION: Patients with a perineal infection after an abdominoperineal
      resection have an increased incidence of local recurrence. However, there was no
      association between abdominal sepsis and prognosis after surgery for rectal
      cancer.

PMID- 12068188
TI  - Prospective, randomized trial comparing sigmoid vs. descending colonic J-pouch
      after total rectal excision.
AB  - PURPOSE: The aim of this study was to compare the bowel function of sigmoid vs.
      descending colonic J-pouches after ultralow anterior resection for rectal cancer.
      METHODS: A prospective, randomized trial was conducted from March 1998 to
      September 1999. Ninety-two consecutive patients undergoing ultralow anterior
      resection for cancers arising from 3 to 10 cm from the anal verge were recruited.
      Forty-eight patients were males; the mean ages (standard error of the mean) for
      patients with sigmoid and descending colon pouches, respectively, were 65.2 (3.1)
      years and 62.3 (3.1) years. A total of 46 patients were randomly assigned to each
      group. Two patients from each group were excluded; abdominoperineal resection was
      performed for two patients in the sigmoid pouch group and one patient in the
      descending pouch group. One patient in the descending pouch group had a transanal
      resection of a benign polyp. Dukes staging and use of postoperative
      chemoradiotherapy were statistically similar in both groups. All patients
      underwent a standardized ultralow anterior resection. A defunctioning loop
      ileostomy was used routinely. Anorectal physiology and bowel function
      questionnaires were performed at six weeks after ileostomy closure and again at 6
      and 12 months after surgery. RESULTS: Median follow-up was 12 (range, 7 to 25)
      and 12 (range, 6 to 25) months, respectively, for sigmoid and descending pouch
      groups. Median tumor and anastomotic heights, time to ileostomy closure,
      operative time, and postoperative stay were statistically similar in both groups.
      There were no significant differences in stool frequency, incontinence, urgency,
      use of pads and antidiarrheals, sensation of incomplete evacuation, and anorectal
      physiology results between groups (P > 0.05). CONCLUSION: Pouches made from
      sigmoid or descending colon give similar bowel function after ultralow anterior
      resection for rectal cancers.

PMID- 12068189
TI  - Microsatellite instability as a marker in predicting metachronous multiple
      colorectal carcinomas after surgery: a cohort-like study.
AB  - PURPOSE: In case-control studies, it was reported that microsatellite instability
      might be helpful in predicting the development of metachronous multiple
      colorectal cancers. The purpose of this cohort-like study was to determine
      whether microsatellite instability is a novel independent marker in predicting
      metachronous colorectal carcinomas after colorectal cancer surgery. METHODS:
      Three hundred twenty-eight colorectal carcinoma patients were surveyed by
      periodic colonoscopy for at least three years after surgery. Among these, DNA
      from paraffin-embedded sections was available for 272 cases. DNA of these cases
      was studied for six microsatellite markers (five dinucleotide repeats, one
      mononucleotide repeat). Microsatellite instability phenotype was defined as
      alterations in one or more loci. RESULTS: Median follow-up period was 74 months,
      and the median number of colonoscopies was 4.6. The percentage of microsatellite
      instability-positive cases was 26.4 percent (72/272). Seventeen metachronous
      colorectal carcinomas were detected during the follow-up period. Incidences of
      metachronous colorectal carcinomas in microsatellite instability-positive and
      microsatellite instability-negative cases were 15.3 and 3 percent, respectively
      (P < 0.001). The cumulative five-year incidence of metachronous colorectal
      carcinomas was significantly higher in microsatellite instability-positive cases
      than in microsatellite instability-negative cases (12.5 vs. 2.5 percent, P <
      0.0001). Logistic regression analysis of the relationship between incidence of
      metachronous colorectal carcinomas and possible risk factors (namely, coexistence
      of adenoma at the time of surgery, family history of colorectal carcinoma,
      history of extracolonic malignancy, and microsatellite instability status) showed
      that microsatellite instability and coexistence of adenoma were significant
      independent risk factors for the occurrence of metachronous colorectal
      carcinomas, with values of P = 0.001 and 0.02, respectively. CONCLUSION: These
      data indicate that microsatellite instability can be regarded as a novel
      independent and important marker for predicting the development of metachronous
      colorectal carcinoma after surgery.

PMID- 12068190
TI  - Effects of a hyaluronan-based membrane (Seprafilm) on intraperitoneally
      disseminated human colon cancer cell growth in a nude mouse model.
AB  - PURPOSE: The purpose of this study was to examine whether a hyaluronan-based
      membrane (Seprafilm Adhesion Barrier) could affect growth and metastasis of colon
      cancer in a human xenograft/nude mouse model. METHODS: Male athymic (nude) mice
      underwent a midline abdominal incision followed by an intraperitoneal inoculation
      of KM12-L4 human colon cancer cells. Seprafilm membrane was placed under the
      incision or on the right lateral abdominal wall; control groups received no
      Seprafilm membrane. In another group, Vicryl mesh was placed on the right lateral
      abdominal wall and removed after 1 minute to control for surgical trauma
      associated with biomaterial placement. RESULTS: Intraperitoneal Seprafilm did not
      affect human colon cancer tumor metastasis, including the liver, spleen, and
      mesenteric lymph nodes. The application of a biomaterial such as Seprafilm or
      Vicryl mesh to the peritoneal sidewall away from the midline wound was associated
      with an increased rate of local tumor growth. This was likely because of the
      local trauma of biomaterial placement in the nude mouse model and not because of
      the presence of a foreign material. CONCLUSIONS: Our study suggests that
      Seprafilm does not affect tumor metastasis. Additionally, placement of
      biomaterials may cause local trauma that stimulates the formation of localized
      sidewall tumors in the nude mouse model. Further studies in other animal models
      and ultimately, in humans are required to unambiguously understand the safety of
      Seprafilm and other biomaterials in cancer patients.

PMID- 12068191
TI  - Letter to the Editor.

PMID- 12068192
TI  - Long-term outcome of overlapping anal sphincter repair.
AB  - PURPOSE: This study reviews the long-term outcome of overlapping anal
      sphincteroplasty for acquired anal incontinence. METHODS: Seventy-one consecutive
      patients underwent overlapping sphincteroplasty from 1989 to 1996 Current degree
      of continence and associated quality of life were determined by telephone
      interview using the Fecal Incontinence Severity Index and Fecal Incontinence
      Quality of Life Scale, as validated by The American Society of Colon and Rectal
      Surgeons. Both the patient-rated and the surgeon-rated Fecal Incontinence
      Severity Index scores were recorded. Demographic and perioperative data were
      obtained from patient charts. RESULTS: Forty-nine (69 per cent) of the 71
      patients, with a median age of 38.5 (range, 22-80) years, could be contacted at a
      median of 69 (range, 48-141) months after sphincter repair. Four patients were
      diverted at the time of follow-up. Twenty-four (54 percent) patients were
      incontinent to liquid or solid stool, and only six patients (14 percent) were
      totally continent. Fifteen patients (34 percent) had the best possible Fecal
      Incontinence Quality of Life score of 16. The median patient-rated and surgeon
      rated Fecal Incontinence Severity Index scores were 20 (range, 0-61) and 20
      (range, 0-57), respectively. The patient-rated score correlated to the surgeon
      rated score (r = 0.98, P < 0.001) and the Fecal Incontinence Quality of Life
      score (r = 0.64, P < 0.001). CONCLUSION: Years after sphincter repair surgery
      more than half of the patients are incontinent to liquid or solid stool. The
      American Society of Colon and Rectal Surgeons-validated Fecal Incontinence
      Severity Index and Fecal Incontinence Quality of Life scores are useful and
      complementary tools for evaluation of fecal incontinence.

PMID- 12068193
TI  - Fecal incontinence severity index after fistulotomy: a predictor of quality of
      life.
AB  - PURPOSE: The purpose of this study was to use the Fecal Incontinence Severity
      Index to assess fecal incontinence after fistulotomy and to correlate the Fecal
      Incontinence Severity Index score with quality-of-life measures. METHODS: A
      retrospective chart review was performed on consecutive patients undergoing
      fistulotomy by a single colon and rectal surgeon at a university hospital from
      1991 to 1999. Demographics, fistula anatomy, surgical technique, and length of
      follow-up were recorded. Mailed questionnaires and telephone interviews were
      conducted to determine the Fecal Incontinence Severity Index score, pad usage,
      lifestyle restriction, and psychosocial factors. A linear regression model was
      used to determine the relationship of clinical factors with Fecal Incontinence
      Severity Index. One-way ANOVA was used to correlate Fecal Incontinence Severity
      Index with quality-of-life measures. RESULTS: Of 110 patients who underwent
      fistulotomy, 96 (88 percent) had complete follow-up. Mean age was 48 (range, 17
      84) years, and 68 percent were male. Follow-up was less than two years in 26
      percent, two to five years in 39 percent, and more than five years in 35 percent.
      Of these patients, 41 percent had intersphincteric fistulas, whereas 59 percent
      had transsphincteric fistulas. Median Fecal Incontinence Severity Index score was
      6, with a mean of 13 (maximum Fecal Incontinence Severity Index = 61); 36 percent
      had a Fecal Incontinence Severity Index score of zero. Linear regression revealed
      that only the amount of external sphincter divided correlated with Fecal
      Incontinence Severity Index score (P = 0.05). Quality-of-life measures strongly
      correlated with Fecal Incontinence Severity Index by analysis of variance (P <
      0.01 for pad usage, lifestyle restriction, depression, and embarrassment), with
      substantial quality-of-life drop-off documented with Fecal Incontinence Severity
      Index >30. CONCLUSION: The Fecal Incontinence Severity Index is an excellent tool
      to gauge quality of life after fistulotomy. Fecal Incontinence Severity Index
      scores >30 predict a detrimental effect on quality of life.

PMID- 12068194
TI  - Harmonic scalpel hemorrhoidectomy: five hundred consecutive cases.
AB  - PURPOSE: The aim of this study was to evaluate the incidence of postoperative
      complications after Harmonic Scalpels hemorrhoidectomy and to identify any
      predisposing factors leading to postoperative complications. METHODS: Five
      hundred consecutive cases of Harmonic Scalpel hemorrhoidectomy were studied in a
      prospective manner. Postoperative complications were recorded, and any
      predisposing factors were evaluated. RESULTS: Three hundred fifty-five patients
      (71 percent) underwent Harmonic Scalpel hemorrhoidectomy alone. One hundred
      twenty patients (24 percent) underwent additional fissurectomy/sphincterotomy for
      fissure-in-ano, and 25 patients (5 percent) underwent additional fistulotomy. A
      total of 24 (4.8 percent) patients experienced some form of postoperative
      complication. Three patients (0.6 percent) experienced a secondary postoperative
      hemorrhage requiring reexploration under anesthesia. Two of the three patients
      were taking postoperative oral Toradol, and both had undergone an "open"
      hemorrhoidectomy technique. The third patient required suture ligation of
      multiple bleeding sites on two separate occasions at 7 and 14 days
      postoperatively. The patient was subsequently diagnosed as having Ehlers-Danlos
      syndrome. One patient experienced postoperative incontinence to flatus and stool.
      The patient had large, Grade TV postpartum hemorrhoids and had undergone a three
      quadrant closed hemorrhoidectomy. The sphincter mechanism was intact on
      postoperative ultrasound, and an underlying pudendal neuropathy likely
      contributed to the sphincter dysfunction. Postoperative urinary retention was
      noted in 10 (2 percent) patients, postoperative fissure in 5 (1 percent), and
      abscess/fistula in 4 (0.8 percent). One patient (0.2 percent) required
      readmission for colonic pseudo-obstruction. CONCLUSION: Harmonic Scalpel
      hemorrhoidectomy is a safe surgical modality, and postoperative complication
      rates compare favorably with previously published studies. The combination of an
      "open" hemorrhoidectomy technique and prolonged oral Toradol administration may
      result in a higher incidence of postoperative hemorrhage.

PMID- 12068196
TI  - Letter to the Editor.

PMID- 12068195
TI  - Early experience with stapled hemorrhoidectomy in the United States.
AB  - INTRODUCTION: We report the early results of patients treated with stapled
      hemorrhoidectomy, which has recently been introduced into the United States.
      METHODS: Sixty-eight patients with symptomatic hemorrhoids were treated at two
      institutions with the Proximate HCS Hemorrhoidal Circular Stapler supplied by
      Ethicon Endo-Surgery. Patients were prospectively evaluated for functional
      recovery and postoperative pain on a 1 to 10 scale. RESULTS: There were 45 (66
      percent) males and 23 (34 percent) females with a mean age of 56 years and median
      duration of symptoms of 5 years. The mean operative time was 22.2 minutes. The
      operation was performed with spinal (50 percent), local (40 percent), or general
      (10 percent) anesthesia and as an outpatient (56 percent) or overnight admission
      (44 percent). Ninety-three percent of patients remained asymptomatic with a mean
      follow-up of 34 weeks, whereas the remaining 7 percent required either surgical
      excision or rubber band ligation for persistent symptoms. There was no mortality,
      new incontinence, fecal impaction, or persistent pain. The total morbidity was 19
      percent, with urinary retention as the most common complication (12 percent). The
      mean pain score decreased from 3.6 on postoperative Day 1 to 1.4 at postoperative
      Day 7. Ninety-nine percent of patients made a complete functional recovery by
      postoperative Day 7. CONCLUSIONS: Stapled hemorrhoidectomy is safe, effective,
      and can be performed as an outpatient procedure with local or regional
      anesthesia. There seems to be minimal postoperative pain and early recovery,
      although a benefit over traditional hemorrhoidectomy needs to be proven in a
      randomized trial.

PMID- 12068197
TI  - The perineorectal reflex The perineorectal reflex in health and obstructed
      defecation.
AB  - PURPOSE: Many females with obstructed defecation apply digital pressure on their
      perineum to facilitate defecation. This study investigated the impact of this
      maneuver on rectal tone. METHODS: Forty-five female patients with obstructed
      defecation were studied. Thirty-four patients (76 percent) regularly applied
      digital pressure on their perineum to facilitate defecation. Total colonic
      transit time was normal in 32 patients and prolonged in 13 patients. For
      comparison, 17 female controls were studied. With the subject in the left lateral
      position, a thin, "infinitely" compliant polyethylene bag was inserted into the
      rectum at 10 cm from the anal canal. Rectal tone was assessed by measuring
      variations in bag volume with a computer-controlled electromechanical air
      injection system. After an adaptation period of 15 minutes, digital pressure was
      applied to the anterior perineum by one of the authors (WRS). In a second
      recording session, the tonic response of the rectum to an evoked urge to defecate
      was examined. RESULTS: During the application of perineal pressure, all controls
      showed an increase in rectal tone (mean value, 52.8+/-19 percent). In the whole
      patient group, this response was significantly lower (mean value, 24.2+/-19
      percent; P < 0.001). Eight of these patients (18 percent) showed no response at
      all. None of them applied perineal pressure. In the remaining 37 patients (72
      percent), the perineorectal reflex was present but was significantly lower (mean
      value, 29.8+/-17 percent; P < 0.001). Thirty-four of these females (92 percent)
      stated that they applied perineal pressure on a regular basis to facilitate their
      defecation. All controls showed an increase in rectal tone during an evoked urge
      to defecate (mean value, 37.8+/-8 percent). In the patients, this response was
      significantly lower (16.7+/-6 percent). Eight of these patients showed no
      increase in rectal tone at all. These patients were the same patients in whom the
      perineorectal reflex was absent. Regarding the tonic response of the rectum to
      perineal pressure, no difference was found between patients with a normal colonic
      transit time and those with a prolonged colonic transit time. CONCLUSION: Digital
      pressure applied on the perineum results in an increase in rectal tone. This
      perineorectal reflex is present, although significantly lower, in the majority of
      females with obstructed defecation. This observation might explain why females
      with obstructed defecation frequently apply perineal pressure to facilitate
      defecation.

PMID- 12068198
TI  - Recurrence after abdominal surgery for Crohn's disease: relationship to disease
      site and surgical procedure.
AB  - PURPOSE: We investigated the hypothesis that there is an "aggressive" subtype of
      Crohn's disease characterized by early recurrence and that disease location and
      surgical procedure are associated with differing patterns of recurrence. METHODS:
      We analyzed 280 patient records totaling 482 major abdominal operations from a
      prospectively compiled Crohn's disease database. Patterns of recurrence, as
      defined by reoperation, were analyzed by Kaplan-Meier plots and log-rank tests
      for the group as a whole, as well as according to disease location and operation
      performed using log-rank and Cox regression analysis. RESULTS: The overall
      survival curve followed a simple curve with no apparent early rise in recurrence.
      There was a significantly higher recurrence rate for ileal disease than for
      ileocolic or colic disease (median reoperation-free survival, 37.8 vs. 47.8 and
      54.7 months, respectively; log-rank test = 13.6; P = 0.001), and there was a
      significantly shorter reoperation-free survival for those patients treated by
      strictureplasty alone or stricture-plasty combined with resection than for those
      treated by resection alone (41.7 and 48.6 vs. 51 months, respectively; log-rank
      test = 12; P = 0.002), but only disease site was confirmed as an independent risk
      factor for recurrence by multiple regression analysis. CONCLUSIONS: These data
      suggest that there is no evidence for the existence of a separate, early
      recurring, aggressive disease type. Shorter reoperation-free survival after
      strictureplasty may reflect patterns of recurrence in ileal disease.

PMID- 12068199
TI  - Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not
      for familial adenomatous polyposis.
AB  - PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical
      treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis
      occurs mainly in patients with a background of ulcerative colitis, although the
      reasons for this are unknown. The aim of this study was to characterize
      differences in pouch bacterial populations between ulcerative colitis and
      familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh
      stool samples were collected from patients with ulcerative colitis pouches (n =
      10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis
      ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria
      were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent
      (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from
      familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy
      effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium
      perfringens counts were increased relative to ileostomy counts in patients with
      ulcerative colitis. Total pouch enterococci and coliform counts were also
      increased relative to ileostomy levels. There were no significant quantitative or
      qualitative differences between pouch types when these bacteria were evaluated.
      CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a
      background of ulcerative colitis. Not all ulcerative colitis pouches harbor
      sulfate-reducing bacteria because two ulcerative colitis pouches in this study
      were free of the latter. They are not present in familial adenomatous polyposis
      pouches or in ileostomy effluent collected from patients with ulcerative colitis.
      Total bacterial counts increase in ulcerative colitis pouches after stoma
      closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium
      perfringens, enterococci, and coliforms were similar in both pouch groups.
      Because sulfate-reducing bacteria are specific to ulcerative colitis pouches,
      they may play a role in the pathogenesis of pouchitis.

PMID- 12068200
TI  - Relationship between the platelet activating factor acetylhydrolase gene and
      intractability of ulcerative colitis.
AB  - PURPOSE: Platelet activating factor, which is a potent mediator of inflammatory
      injury in ulcerative colitis, is inactivated by platelet activating factor
      acetylhydrolase. Recently, a point mutation (G994 to T transversion) was observed
      in exon 9 of the platelet activating factor acetylhydrolase gene, and this
      mutation was found to be associated with a decrease in platelet activating factor
      acetylhydrolase activity in plasma. The aim of this study was to determine
      whether the gene mutation was associated with the severity of ulcerative colitis.
      METHODS: We studied 53 patients with ulcerative colitis and 108 control subjects.
      The plasma platelet activating factor acetylhydrolase genotype was determined as
      representative cases with three different genotypes (GG, GT, and TT) by an allele
      specific polymerase chain reaction. RESULTS: There was no significant difference
      in genotypic frequency (GG, GT, and TT genotype frequencies were 68, 30, and 2
      percent in controls and 55, 45, and 0 percent in ulcerative colitis patients).
      Platelet activating factor acetylhydrolase activity in plasma was also measured
      and did not differ significantly between ulcerative colitis patients and controls
      (1.50+/-0.12 vs. 1.81+/-0.34 nmol/min/50 microl, P = 0.60). However, according to
      the relationship between the platelet activating factor acetylhydrolase gene
      mutation and clinical characteristics of ulcerative colitis patients, the
      operative ratio cause of unresponsiveness to steroid therapy was significantly
      higher in patients with the GT genotype than in those with the GG genotype (66.7
      vs. 27.6 percent, P = 0.019). CONCLUSION: We conclude that steroid-nonresponsive
      ulcerative colitis patients have a high frequency of the platelet activating
      factor acetylhydrolase gene mutation. Therefore, genotyping of this gene may be a
      useful marker to predict responsiveness to steroid therapy.

PMID- 12068201
TI  - A low-morbidity murine model of peritonitis.
AB  - PURPOSE: Peritonitis continues to be a major source of mortality and morbidity in
      patients undergoing abdominal surgery. The aim of this study was to develop a
      nonfatal model of bacterial peritonitis in mice so that we could study aspects of
      the pathobiology and treatment of peritonitis in an in vivo model. METHODS: Mice
      were inoculated via a midline laparotomy with 0.5 mg of zymosan in 0.1 ml of
      saline into the subomental space. At 24, 48, and 96 hours after treatment,
      animals were killed, and analysis was performed to determine the degree of
      peritoneal inflammation. End points included intraperitoneal cellular influx,
      tumor necrosis factor-alpha concentrations, and myeloperoxidase activity. In
      addition, peritoneal lavage fluid was plated onto blood agar for analysis of
      bacterial colony-forming units. There were 40 mice in each group. RESULTS: There
      were no deaths in either group. Facultative Gram-negative bacteria were cultured
      from the peritoneal cavities of zymosan-treated animals at 24 and 48 hours after
      insult (colony-forming unit counts of 92+/-11 vs. 0 in control animals). In the
      zymosan-treated animals, there were significantly increased numbers of
      inflammatory cells (especially neutrophils) in the peritoneal cavity at 24 and 48
      hours after treatment; these numbers returned to control levels by 96 hours.
      Myeloperoxidase activity was also elevated both in the peritoneal fluid (2.4 X
      10(-4) units/ml compared with 1.6 x 10(-4) units/ml, P < 0.05) and in remote
      organs (i.e., lung, P < 0.05; liver, P < 0.001; and kidney, P < 0.05) at 24 hours
      after treatment. There was no significant difference in tumor necrosis factor
      alpha levels between zymosan-treated and control mice in either serum or
      peritoneal fluid at any time point investigated. There was no mortality in either
      the zymosan-treated or control animals. CONCLUSION: In this model of bacterial
      peritonitis in mice, we have demonstrated how the peritoneal cavity can resolve a
      relatively localized inflammatory insult within 96 hours of induction. This
      response is characterized by a cellular influx of predominantly neutrophils and
      macrophages and by pronounced oxidative activity. We will use this in vivo model
      to characterize aspects of the pathobiology and treatment of peritonitis.

PMID- 12068203
TI  - Anoperineal tuberculosis: diagnostic and management considerations in seven
      cases.
AB  - PURPOSE: Anoperineal tuberculosis is a rare extrapulmonary form of the disease
      that we must learn to recognize because it requires specific treatment. METHODS:
      Data from seven patients with anoperineal tuberculosis observed in a Parisian
      proctology unit between 1982 and 1999 were reviewed. RESULTS: All the patients
      were male (median age, 55 years); five were born in underdeveloped countries, and
      two were still living there. The average length of time between first
      manifestation of the disease and diagnosis was three years (range, 3 months to 9
      years); all patients had undergone surgery previously. There were six recurring
      anal fistulas (complex in 5 cases) and one recurring abscess. In every case, the
      diagnosis had been suspected or confirmed by systematic histologic study of the
      surgically excised tissue. An association with pulmonary tuberculosis was found
      in each case. Treatment included two parts: conventional surgical treatment of
      anal sepsis and specific medical antituberculosis treatment. Evolution was
      favorable in all cases, with no recurrence of disease. Human immunodeficiency
      virus infection did not increase the incidence of anoperineal tuberculosis.
      CONCLUSION: Tuberculosis should be suspected in all recurrent fistulas.
      Histologic examination of the excised tissue and a lung x-ray should be performed
      to avoid delay in diagnosing an easily curable disease.

PMID- 12068202
TI  - Self-expandable stent before elective surgery vs. emergency surgery for the
      treatment of malignant colorectal obstructions: comparison of primary anastomosis
      and morbidity rates.
AB  - PURPOSE: At present there are not enough studies that demonstrate the usefulness
      of self-expandable stents in patients with left-sided malignant colon and rectal
      obstruction. We evaluated primary anastomosis and morbidity rates obtained with
      this method in comparison with the results of the emergency surgical treatment.
      METHODS: From February 1994 to November 1999, 72 consecutive patients with left
      sided malignant colorectal obstruction were enrolled. Forty-three patients were
      assigned to the study group (preoperative stent and elective surgical treatment
      or palliative stent, depending on the assessment of the stage of the tumor) and
      29 to the control group (emergency surgical treatment). The resection was not
      indicated in 18 cases in the study group (after preoperative staging in 17 and
      intraoperative staging in 1) and in 3 cases in the control group. RESULTS: In the
      study group, the obstruction was relieved in 41 cases (95 percent) after the
      stent placement. Of 26 patients who underwent surgical treatment, a primary
      anastomosis was possible in 22 (84.6 vs. 41.4 percent in the control group, P =
      0.0025), with lower need for a colostomy (15.4 vs. 58.6 percent in the control
      group). The anastomotic failure rate was similar and the reintervention rate was
      lower (0 vs. 17 percent, P = 0.014). The total stay (14.23 vs. 18.52 days; P =
      0.047), the intensive care unit stay (0.3 vs. 2.9 days; P = 0.015), and the
      number of patients with severe complications (11.6 vs. 41.2 percent; P = 0.008)
      were significantly lower in the study group. CONCLUSIONS: In our patients with
      left-sided malignant colon and rectal obstruction, placement of a preoperative
      stent prevented 17 (94 percent) of 18 of unnecessary operations and a large
      number of colostomies after elective surgery. These results were obtained with a
      lower severe complication rate as well as a shorter hospital stay.

PMID- 12068204
TI  - T-pouch: a new valve design for a continent ileostomy.
AB  - PURPOSE: After proctocolectomy for ulcerative colitis or familial adenomatous
      polyposis, creation of a continent ileostomy is one of the surgical options.
      Although most patients will be offered a pull-through procedure, the continent
      ileostomy is a valuable alternative in patients who are either not candidates for
      or have failed an ileal pouch-anal anastomosis or who--for other reasons--prefer
      a permanent ileostomy. The traditional continent reservoirs (Kock or Barnett
      pouch) with an intussuscepted bowel segment as valve mechanism have an
      unsatisfactorily high incidence of dysfunction and frequent reoperations. The
      objective of this study was to adapt the T-pouch valve concept, previously used
      for urinary reservoirs, for a continent stool reservoir and to construct a valve
      mechanism that omits intussusception of the bowel and maintains the blood supply
      to the valve segment. METHODS: The technique for the critical valve construction
      is described in detail. It consists of isolating the terminal segment of the
      small bowel with its blood supply. The valve mechanism is created by embedding
      this segment in a serosa-lined tunnel of two apposed limbs of bowel that will
      form the pouch reservoir. RESULTS: Preliminary results in six patients indicate
      complete continence of the pouch. CONCLUSION: Although long-term results are not
      yet available, the new T-pouch concept is suitable as a continent stool reservoir
      and promises a significant improvement as compared with the traditional Kock
      pouch.

PMID- 12068205
TI  - Modified Longo's hemorrhoidectomy.
AB  - The Longo technique of stapled hemorrhoidectomy is rapidly gaining world-wide
      acceptance. However, hemorrhoids with large external components are often left
      with troublesome skin tags after the Longo technique. In this article we present
      modifications to the Longo technique that make it easier to perform and provide
      adequate treatment of hemorrhoids that have a significant external component or
      skin tags.

PMID- 12068206
TI  - Adenocarcinoma below ileoanal anastomosis for ulcerative colitis: report of a
      case and review of the literature.
AB  - BACKGROUND: Restorative proctocolectomy with hand-sewn ileoanal anastomosis and
      mucosectomy is warranted in patients with dysplasia and/or cancer on ulcerative
      colitis to prevent subsequent neoplastic changes in the retained mucosa. However,
      complete excision of the colonic mucosa cannot be obtained reliably. We report a
      case of anal canal adenocarcinoma after handsewn anastomosis with mucosectomy.
      METHODS: A 47-year-old patient, previously submitted to ileorectal anastomosis
      for colonic cancer on ulcerative colitis, underwent completion proctectomy and
      handsewn ileoanal anastomosis with mucosectomy for recurrent anastomotic cancer.
      Two years later, we submitted the patient to pouch removal with permanent
      ileostomy for a mucinous adenocarcinoma of the anal canal (T2N2Mx) found at
      follow-up pouch endoscopy. CONCLUSIONS: Only four cases of adenocarcinoma after
      handsewn anastomosis have been reported in the literature. This new case we
      report confirms that the risk of malignancy after ileoanal anastomosis with
      mucosectomy, although small, is real, despite the surgeon taking care with this
      particular step of the procedure. Careful surveillance is needed in patients with
      surgical treatment for long-term ulcerative colitis or dysplasia.

PMID- 12068207
TI  - Takayasu's arteritis after total proctocolectomy for ulcerative colitis: report
      of a case.
AB  - PURPOSE: Although coexistence of Takayasu's arteritis with ulcerative colitis is
      often reported, all these cases have been in patients whose colons were in situ.
      The aim of the present study was to describe a patient who developed Takayasu's
      arteritis after total proctocolectomy for ulcerative colitis. METHODS: The
      clinical course of a 42-year-old female who developed Takayasu's arteritis after
      total proctocolectomy for ulcerative colitis is described and the literature
      reviewed. RESULTS: Symptomatic arteritis developed in the left carotid artery
      four months after total proctocolectomy with ileal J-pouch-anal anastomosis for
      ulcerative colitis. Peristomal pyoderma gangrenosum, multiple ulcers in the oral
      cavity, and leakage at the ileoanal anastomosis were observed simultaneously.
      High-dose therapy with steroids proved effective for the arteritis, pyoderma
      gangrenosum, and multiple oral ulcers. We finally excised the ileal pouch with
      anus because of the intractable leakage three years after the occurrence of
      Takayasu's arteritis. CONCLUSIONS: This patient illustrates the possibility that
      Takayasu's arteritis is an extraintestinal complication of ulcerative colitis
      even after surgical removal of the colon.

PMID- 12068208
TI  - Ischemic colitis caused by strict dieting in an 18-year-old female: report of a
      case.
AB  - Ischemic colitis is typically limited to elderly patients who have concomitant
      disorders such as cardiovascular disease and chronic renal failure, but rarely
      affects a young person. The patient was an 18-year-old Japanese female who
      started dieting to obtain a slim figure three months before admission and
      presented with a two-month history of constipation and a sudden onset of lower
      abdominal pain and bloody diarrhea. She underwent colonoscopy, which revealed
      edema, hemorrhages, and several longitudinal shallow ulcers in the descending
      colon. Stool and blood culture results were negative for pathogens. She improved
      rapidly within five days without any specific therapies except intravenous
      hydration and anticholinergic agents, under the diagnosis of ischemic colitis. In
      this case constipation and dehydration associated with dieting seemed to be
      responsible for the development of ischemic colitis. We recommend that ischemic
      colitis should be included in the differential diagnosis of colitis with
      bleeding, even in patients younger than age 20 who do not have any predisposing
      factors.

PMID- 12068213
TI  - Use of the latissimus dorsi flap for recontouring and augmentation after TRAM
      flap breast reconstruction.
AB  - The transverse rectus abdominis musculocutaneous (TRAM) flap is the most commonly
      used autogenous tissue flap for breast reconstruction. However, it may not
      provide sufficient volume in all patients to match the contralateral breast.
      Insufficient abdominal bulk or bilateral reconstructions limit the amount of
      tissue available for the TRAM flap. Partial flap loss from fat necrosis or
      radiation injury may result in contour deformities of the reconstructed breast.
      Additional soft-tissue augmentation and contouring may be necessary to produce
      adequate volume, contour, and symmetry. The authors present 7 patients who
      underwent latissimus dorsi flap reconstruction to correct volume and contour
      abnormalities that developed after TRAM flap breast reconstruction. Preservation
      of the serratus branch of the thoracodorsal vessels allows this flap to be used
      even after free TRAM flap reconstruction.

PMID- 12068214
TI  - Effects of managed care on teaching, research, and clinical practice in academic
      plastic surgery.
AB  - The aim of this study was to determine: 1) if there have been changes in
      teaching, research, and clinical practice in academic plastic surgery in recent
      years; and 2) if there have been, are they associated with changes in the managed
      care environment? Gaining a clearer perspective on how managed care affects
      academic plastic surgery will enable academicians to define better the problems
      and opportunities they face mutually and to respond effectively to these issues.
      This study used a cross-sectional study design. Reference time periods were the
      premanaged care era (1990-1991) versus the current time (1997-1998). Data were
      collected by questionnaires sent to 94 academic program directors in plastic
      surgery. The main independent variable of managed care was measured as the
      difference in the percent of income from health maintenance organizations
      generated by each program in 1990 to 1991 versus 1997 to 1998. The dependent
      variables of teaching, research, and clinical practice were measured by the
      percentage of time spent in each category, the number of work hours per week, the
      number of staff personnel, the location of teaching, the number of grants and
      publications, and the percentage of reconstructive and cosmetic cases in 1990 to
      1991 versus 1997 to 1998. Univariate analysis, paired Student's t-test, Fisher's
      exact test, Pearson's correlation, Spearman's correlation, and linear regression
      were used to establish significance (alpha = 0.05) of the effects of managed care
      on dependent variables. Sixty-six questionnaires were completed and returned (70%
      response rate). There were significant changes in the managed care environment,
      clinical practice (operating room and clinics), and research in academic plastic
      surgery from 1990 to 1997. The percentage of income generated from managed care
      increased from 9.8% (of total revenue) in 1990 to 23.6% in 1997 (an increase of
      13.8%; p < 0.0001). Academic plastic surgeons were found to spend significantly
      more time in clinical practice (3% more of total time spent; 5.3 hours more per
      week in 1997; p < 0.016). This change correlated significantly with the increase
      in managed care (p < 0.015). In addition, the percentage of cosmetic cases
      increased from 18.0% in 1990 to 28.3% in 1997 (p < 0.001), and that of
      reconstructive surgery was reduced proportionately (p < 0.001). Also, a
      significant decrease in the time spent for research was observed (mean reduction,
      2.8 hours less per week; p < 0.001). Although the trend was to a lower number,
      there were no significant changes in the amount of time spent in teaching (p >
      0.08) and in administrative duty (p > 0.06), or in the number of personnel
      employed in the teaching programs (p > 0.05). In summary, these findings suggest
      that: 1) a greater percentage of revenue was generated from managed care in 1997
      than in 1990, indicating a growing fiscal influence by managed care on academic
      plastic surgery; 2) furthermore, this change is associated with academic plastic
      surgeons devoting more time to clinical practice and less time to research
      endeavors; and 3) although managed care policies do affect teaching adversely,
      this effect has not yet reached significance for the period examined during this
      study.

PMID- 12068215
TI  - Taste and olfactory disturbances after upper and middle third facial fractures: a
      preliminary study.
AB  - To estimate smell and taste after traumatic disturbances, the authors questioned
      a sample of 92 patients who underwent surgical treatment for upper third and/or
      middle third facial fractures between January 1, 1988, and May 31, 1996, at the
      Department of Maxillofacial Surgery, University of Rome "La Sapienza," Italy. A
      total of 86 patients included in the study had a facial fracture sustained during
      a motor vehicle accident. Twenty-nine patients reported smell and/or taste after
      the traumatic disturbance. Of these 29 patients, 8 patients had hyposmia and/or
      anosmia without taste deficit, 10 patients had taste disturbances without smell
      loss, and 11 patients noted disturbance in both smell and taste. The authors
      encountered posttraumatic smell disturbances in 19 patients in their sample.
      Nasozygomatic-Le Fort fractures, fronto-orbital fractures, and pure Le Fort
      fractures were found to determine posttraumatic smell disturbances in these 19
      patients. Nasal fractures, nasoorbital-ethmoidal fractures, ethmoidal fractures,
      frontal-Le Fort fractures, and nasal-Le Fort fractures did not determine any
      olfactory dysfunction. Posttraumatic hypogeusia and ageusia were found in 21
      patients and was caused by nasozygomatic-Le Fort fractures, fronto-orbital
      fractures, and pure Le Fort fractures. The authors did not find any taste
      deficits after patients sustained other kinds of facial fractures. In the 11
      patients observed, disturbances in both smell and taste were noted. Nasozygomatic
      Le Fort fracture was the most common in these 11 patients. At 5 years' of follow
      up, the results indicate that hypogeusia and hyposmia are connected with the
      etiology of fracture, the violence of the trauma, and the involvement of specific
      facial bone regions.

PMID- 12068216
TI  - Comparative study of the extent of palatal lengthening by different methods.
AB  - Palatal lengthening is often emphasized in performing palatoplasty. However,
      definitive data regarding the method of measuring palatal length and the extent
      of palatal lengthening expressed quantitatively have not been reported. The
      authors have devised an easy method of measuring palatal length that can be
      expressed quantitatively, and they examined the characteristics of various
      methods of palatoplasty that are presently used commonly. A paper ruler was used
      to measure both a straight-line and a curved distance while the patient was under
      general anesthesia before and immediately after the palatoplasty. According to
      this study, the straight-line distance was lengthened to a significantly greater
      degree than the curved distance was after pushback palatoplasty for incomplete
      types of cleft palate and two-flap palatoplasty for complete types. Furlow double
      opposing Z-palatoplasty and two-flap palatoplasty appeared to allow for greater
      palatal lengthening than the pushback palatoplasty. Further investigations will
      be undertaken to determine the correlation between the extent of palatal
      lengthening and speech development.

PMID- 12068217
TI  - Bilateral one-stage rotation advancement technique for Saudi children with
      isolated bilateral incomplete cleft lip: low revision rate despite multiple
      imperfections.
AB  - The author is unaware of any article published in the English literature during
      the past 25 years that addresses specifically the results of surgery in isolated
      bilateral incomplete cleft lip deformity. The current study presents the outcome
      and investigates the surgical revision rate in 10 consecutive Saudi children with
      this deformity. Surgery was performed by the same surgeon using the bilateral one
      stage rotation advancement technique. No primary nasal correction was performed
      in any of the patients. There were no immediate postoperative complications. Only
      one patient was offered a revision, but the parents refused and stated that they
      were happy with the result. No secondary lip or nasal correction was suggested or
      planned for any of the other patients. A panel of 10 medical students was asked
      to assess the surgical results using a 10-point scale. The one patient who was
      offered a revision obtained the lowest grade (mean score, 7.5 points). The
      remaining patients had a mean score that ranged between 7.9 points and 9.3
      points. It appears that the multiple imperfections and asymmetries observed in
      the postoperative photographs were not thought to be severe enough to warrant
      surgical revision.

PMID- 12068218
TI  - V-Y fasciocutaneous pudendal thigh flap for repair of perineum and genital region
      after necrotizing fasciitis: modification and new indication.
AB  - Necrotizing fasciitis is an aggressive, deep-seated infection of the fascia and
      subcutaneous fat with necrosis of the overlying skin, and it is a toxin-mediated
      disease. The aim of this study was to review 13 cases of necrotizing fasciitis of
      the perineum and the external genitalia region with regard to the diagnosis,
      treatment, and methods of reconstruction of secondary defects. The study was
      performed from June 1997 to May 2001 and involved 11 men and 2 women who ranged
      in age from 35 to 67 years (mean age, 53 years). All patients presented to the
      plastic surgery unit with huge secondary defects of the urogenital region, upper
      thigh, and lower abdomen after being excised initially by general surgeons. Eight
      patients were treated with bilateral flaps, and the unilateral flap was used in 2
      patients. The V-Y island fasciocutaneous flap, used to resurface the urogenital
      region after necrotizing fasciitis, is considered a new indication. The V-Y axial
      pattern design of the flap is also considered a new modification, which enabled
      the flap to be advanced and tailored nicely in the midline. The idea of using the
      V-Y-plasty design is raised because the perineum has a pair of symmetrical
      anatomic structures. In addition, this procedure conserves tissue and the flap
      donor site is closed primarily without tension. Both aesthetic and functional
      results were satisfactory.

PMID- 12068219
TI  - Evaluation of scars after harvest of the temporoparietal fascial flap depending
      on the design of the skin incision.
AB  - The authors evaluated the conspicuousness of the temporal scar caused by two
      incision patterns after harvesting the temporoparietal fascial flap: a straight
      incision and a zigzag incision. The 27 scars of 27 patients were examined in this
      study. Fifteen patients underwent a straight incision and 12 patients had a
      zigzag incision. This study showed that the zigzag incision resulted in more
      conspicuous scars than the straight incision and that this effect was more
      evident in younger patients than in older patients, at least in Japanese. In a
      comparison of older patients and younger patients irrespective of the skin
      incision patterns, the scars were substantially more conspicuous in the younger
      patients. A simple and short incision is preferred when harvesting the
      temporoparietal fascial flap and more careful management is required for young
      patients.

PMID- 12068220
TI  - Accurate method for determining functional penile length in Turkish young men.
AB  - There are only a few reports that investigate the measurement of functional
      penile length and compare the methods used for this purpose. The aim of this
      study was to determine the correlation between the measurement techniques and to
      determine an appropriate method that correlates the erect state most closely.
      Measurements of penile length in 200 healthy men were made during three different
      states--flaccid, erect, and stretched--of the penis. The results were evaluated
      using descriptive statistics, paired t-test, correlation coefficients, and
      regression equations. The correlation between the flaccid and the erect lengths
      was 71.2%, and it was 80.2% between the stretched and the erect lengths (p <
      0.01). Using regression equations, the degree of accuracy in estimating the erect
      length by using the stretched length was 65.3% (R2 = determination coefficient; p
      < 0.01) and was 50.8% by using the flaccid length (p < 0.01). When both the
      flaccid and the stretched lengths were considered together, the predictability of
      erect length was R2 = 65.5%. The results obtained using different statistical
      methods showed that the most accurate results can be obtained by considering
      stretched penile length, whereas flaccid length had little importance in
      determining erect penile length. In conclusion, the stretched penile length
      measurement technique is highly recommended for the accurate prediction of the
      erect penile length.

PMID- 12068221
TI  - Anthropometric study of alar cartilage in Asians.
AB  - Measurements of 52 alar cartilages in 26 Koreans were obtained for an
      anthropometric study during primary open-approach rhinoplasties. The lateral
      crura were found most commonly to be concave, exhibited in 40% of the male
      patients and in 50% of the female patients. The medial crura were most often
      straight, found in 56% of the male patients and in 46% of the female patients.
      The average length, width, and thickness of the lateral crura were 19.7 mm, 10.5
      mm, and 0.55 mm, respectively, in men; and 16.8 mm, 9.8 mm, and 0.54 mm,
      respectively, in women. The lengths of the columellar and footplate segments of
      the medial crura were 10.0 mm and 7.8 mm in men, and were 8.0 mm and 6.3 mm in
      women. These data suggest that the alar cartilage in Asians, contrary to popular
      myth, is not markedly smaller than that of whites. However, differences were
      found in the configuration of the cartilage and the length of the footplate of
      the medial crus.

PMID- 12068222
TI  - Turnover epineural sheath tube in primary repair of peripheral nerves.
AB  - The epineural repair technique, which is the gold standard of peripheral nerve
      injuries, is still far from being ideal. The purpose of this study was to
      investigate the effects of the turnover epineural sheath tube (TEST) when used
      over the primary nerve repair site to improve nerve regeneration. Twenty-five
      Wistar rats were divided into three groups and were operated. In the sham control
      group, the sciatic nerve was dissected from the sciatic notch to its bifurcation
      and was left intact. In the primary epineural repair group an incision was made
      on the nerve and it was repaired using six epineural sutures. In the TEST group,
      after the incision was made the nerve ends were approximated with two epineural
      sutures. A proximal circular epineural incision was then made to enable the
      epineurium to be turned and slid over the repair site. Functional recovery was
      evaluated by walking tract analysis, and the sciatic functional index was
      calculated. Histomorphometric studies of the sciatic nerves and gastrocnemius
      muscles were also performed 3 months postoperatively. Three months
      postoperatively, functional analysis and nerve and muscle histomorphometric
      studies revealed similar results in the primary repair and TEST groups. There was
      no significant difference (p > 0.05) between the results of the TEST and the
      primary nerve repair groups. However, during the microscopic examination, a
      decrease in both foreign material reaction and an inflammatory response with less
      fibrosis were observed in the TEST group. The TEST has a nerve-healing property
      similar to primary epineural repair, with the advantage of a reduced number of
      sutures, which decreases the fibrosis around the repair site. The TEST is an
      alternative treatment modality among other techniques, especially for
      polyfascicular peripheral nerves.

PMID- 12068224
TI  - Different venous end-to-side microanastomotic techniques: comparative study in a
      new rat model.
AB  - End-to-side venous anastomosis is sometimes necessary when there is the lack of a
      suitable vein, when there is a size discrepancy in the veins to be repaired, or
      when the anastomosis of multiple veins is required. The effects of elliptical vs.
      slit venotomy on vessel patency have not been investigated in a flap model. A
      new, simple, reliable, and reproducible model is described in which the femoral
      vein of the groin flap is anastomosed to the side of the deep dorsal penile vein.
      Elliptical hole and slit venotomies were tested in 26 Sprague-Dawley rats, and
      the anastomoses were 100% patent. The type of venotomy was not found to affect
      patency. Either technique is equally valid in end-to-side venous anastomosis, and
      the model itself is convenient for training.

PMID- 12068223
TI  - Enhancement of muscle flap hemodynamics by angiopoietin-1.
AB  - Angiopoietin-1 (Ang-1) constitutes a novel family of endothelial cell-specific
      angiogenic factors. Ang-1 functions mainly in remodeling, maturation, and
      stabilization of blood vessels. Its direct role in the process of angiogenesis
      remains unknown. The authors designed an experimental study to investigate the
      angiogenic potential of Ang-1 and to determine its hemodynamic effects on the
      cremaster muscle flap model in the rat. Adenovirus-mediated gene therapy was used
      for delivery of Ang-1. The study sample included 45 male Sprague-Dawley rats
      weighing 200 to 250 g. After the cremaster muscle tube flaps were prepared, rats
      were randomized into three different groups of 15 animals. In group I (the
      control), the flaps received phosphate-buffered saline (PBS). In group II, flaps
      were treated with adenovirus vector encoding Ang-1 (Ad-Ang-1). In group III,
      flaps received a control gene encoding green fluorescein protein (Ad-GFP). All
      treatments were administered via intra-arterial injections of either viral
      particles (10(8) placque-forming units) or PBS. The external iliac artery was
      used for this purpose. The cremaster tube flap was then preserved in a
      subcutaneous pocket in the lower limb. The tube flap was withdrawn from the limb
      on days 3, 7, and 14 after intra-arterial injection to evaluate microcirculatory
      measurements such as red blood cell velocity, vessel diameter, capillary density,
      and microvascular permeability by intravital microscopy. Evaluations were
      performed by an investigator who was blinded to treatment groups. In a series of
      control experiments performed with Ad-GFP, adenoviral gene expression was
      evidenced by the observation of shiny GFP deposits along the vessel walls under
      fluorescence microscopy throughout the whole cremaster flap 2 days after
      transfection. At day 3 there was no evidence of any differences in capillary
      density and permeability index (PI). At day 7, the functional capillary density
      was significantly higher in the Ad-Ang-1-treated group compared with the control
      and the Ad-GFP groups (10/hpf +/- 2 vs. 7/hpf +/- 0.5, p = 0.006; 5/hpf +/- 1.6,
      p = 0.0001). The PI in the Ad-Ang-1-treated group was significantly lower
      compared with the Ad-GFP-treated group (1.1/hpf +/- 0.1% vs. 1.4/hpf +/- 0.1%, p
      = 0.0005). At 14 days, the number of the flowing capillaries was significantly
      higher in the Ad-Ang-1-treated group compared with the control and the Ad-GFP
      treated groups (13/hpf +/- 1.7 vs. 9/hpf +/- 2 and 6/hpf +/- 1.3, p = 0.0001).
      The microvascular PI was significantly lower in the Ad-Ang-1-treated group
      compared with the Ad-GFP-treated group (1.3/hpf +/- 0.2% vs. 1.8/hpf +/- 0.5%, p
      = 0.004). Histologically, the cremaster flaps revealed focal and mild
      inflammation regardless of the treatment and time point of evaluation. There was
      evidence of vasculitis in muscles pretreated with Ad-GFP and Ad-Ang-1. In
      summary, in the Ad-Ang-1-treated cremaster flaps, functional capillary density
      increased from 46% at day 7 to 98% at day 14 when compared with the control group
      (p < 0.0001). In conclusion, in this experimental muscle flap model, Ad-Ang-1
      treatment proved to be a successful method of angiogenic therapy, providing a
      long-lasting angiogenic effect over a period of 14 days. The increased capillary
      perfusion accompanied by the formation of more stable and mature vessels
      resistant to fluorescein isothiocyanate-conjugated albumin leakage may serve as
      in vivo evidence that Ang-1 therapy improves skeletal muscle flap hemodynamics.
      These exciting findings raise the possibility that Ang-1 may have implications
      for therapeutic angiogenesis. To the authors' knowledge, their study demonstrates
      for the first time the feasibility of intravascular gene therapy using a virus
      vector in an attempt to enhance muscle flap hemodynamics.

PMID- 12068225
TI  - Effects of nerve growth factor on the neurotization of denervated muscles.
AB  - Studies on surgical repair techniques of the peripheral nerve are still trying to
      improve the outcome. There are many studies on the effects of various
      neurotrophic factors on the transected peripheral nerve. Muscular neurotization,
      which is the direct implantation of the nerve to the target denervated skeletal
      muscle, is one of the techniques used when the primary repair of the peripheral
      nerves is not possible. The effects of nerve growth factor (NGF), which is one of
      the primary neurotrophic factors, on the reinnervation of denervated muscles by
      neurotization is investigated in this experimental study. The denervated soleus
      muscle was neurotized via peroneal nerve implantation (group 1), and NGF was
      administered to the neurotized muscle (group 2). All animals were evaluated at
      weeks 8, 10, and 12 using electromyography. Muscle contractility, muscle weight,
      and histological morphometric tests were performed at week 12. The experimental
      groups were compared with each other and normal control values.
      Electromyographically, group 2 (direct nerve implantation + NGF) demonstrated
      better reinnervation in all evaluations. The study of muscle weight showed that
      the muscle mass was 75% of the normal soleus muscle in group 1 and was 85% of the
      normal side in group 2 at the end of week 12. In group 1, the twitch force was
      56% of the normal soleus muscle and was 71% in group 2. Tetanic force was 53% of
      the normal soleus muscle in group 1 and 68% in group 2. Histological morphometric
      studies revealed that there was a decrease in the density of the motor end plates
      in group 1, but there was no statistically significant difference between the
      normal soleus muscles and the NGF applied to group 2. The positive effects of NGF
      on the neurotization of denervated muscles seen in this study suggest that it may
      be useful for treating some difficult reconstructions caused by denervation.

PMID- 12068226
TI  - Phalloplasty in a female-to-male transsexual using a double-pedicle composite
      groin flap.
AB  - An operative procedure for phalloplasty in a 21-year-old female-to-male
      transsexual is reported that uses a double-pedicle composite groin flap. The
      surgical technique is described. Both the deep and the superficial circumflex
      iliac vessels were included in the pedicle to ensure well-vascularized extended
      skin and bone in the flap. The procedure was planned in two stages to
      prefabricate a neourethra before transfer of the flap. The large skin island and
      bone with its dual blood supply enabled the authors to reconstruct the penis in
      an appropriate size and stiffness without vascular compromise. The flap donor
      site was sutured easily. The patient is pleased with the operative results. His
      voiding and sexual intercourse are acceptable according to his report.

PMID- 12068227
TI  - Split thoracodorsal nerve funicular graft combined with functional latissimus
      dorsi musculocutaneous flap transfer for immediate facial reanimation after tumor
      ablation.
AB  - The authors report a case of immediate facial reanimation resulting from
      functional latissimus dorsi musculocutaneous flap transfer and funicular grafting
      of the thoracodorsal nerve after cheek tumor ablation. After wide excision of the
      tumor, including the facial nerve except the temporal branch and part of the
      zygomatic major muscle and masseter muscle, the authors reconstructed the cheek
      skin and provided movement by performing a small-segment latissimus dorsi
      musculocutaneous flap transfer using Harii's method and the defect of the buccal
      and marginal mandibular branches of the facial nerve by funicular grafting from
      one of the two funicles of the thoracodorsal nerve. After 6 months, the
      transplanted, small-segment latissimus dorsi muscle showed good voluntary
      movement, and the lower orbiculus oris and depressor oris presented good
      functional recovery. The authors believe the two funicles of the thoracodorsal
      nerve can be used independently for two purposes: one for functional segmental
      muscle transfer and the other for nerve grafting to defects of branches of the
      facial nerve. This concept makes it possible to reconstruct multiple facial
      movements while minimizing donor site morbidity by means of immediate facial
      reanimation.

PMID- 12068228
TI  - Use of the orbicularis oculi muscle flap for severe Marcus Gunn ptosis.
AB  - The authors present a 22-year-old man with severe unilateral congenital
      blepharoptosis associated with Marcus Gunn (jaw-winking) syndrome. The best
      conventional treatment was levator excision to eliminate the synkinetic reflex
      and fascia lata brow suspension. However, the previous surgery had some
      disadvantages. Therefore, the authors report the use of the orbicularis oculi
      muscle flap to elevate dynamically the ptotic eyelid and to eliminate the
      synkinetic reflex without levator resection. The postoperative result was both
      functionally and cosmetically satisfactory after 1 year of follow-up.

PMID- 12068229
TI  - Flow-through use of the osteomusculocutaneous free fibular flap.
AB  - A case of a forearm defect resulting from a high-velocity firearm injury was
      reconstructed by flow-through free transfer of the osteomusculocutaneous fibular
      flap harvested from the remaining stump of the patient's left leg that was
      amputated below the knee. The dimensions of the bone defect and damage to
      anatomic structures of more than one type (including ulnar artery, ulnar bone,
      and overlying soft tissue) were the reasons for the treatment approach with a
      composite tissue transfer including vascularized bone. Preoperative radiographic
      and angiographic examination revealed that the amputation stump offered a fibular
      shaft with adequate length and a peroneal artery patent up to the most distal
      point of the bone. Instead of the usual osteocutaneous fibular harvest, flap
      harvest was performed in an osteomusculocutaneous manner with incorporation of a
      segment of soleus muscle with an overlying skin paddle. In addition to the
      replacement of the bone defect, transfer of the flap in a flow-through manner
      reestablished the dual blood supply of the hand by replacing the ulnar artery
      gap, whereas the muscle and skin of the flap allowed three-dimensional
      reconstruction of the complex defect. In severe injuries of the upper extremity,
      flow-through free transfer of the fibular flap provides not only replacement of
      the resulting composite defect but also may offer salvage, or at least
      revascularization, of the extremity when complicated by arterial damage.

PMID- 12068230
TI  - Intraosseous ganglion of the lunate.
AB  - Intraosseous ganglia are occasionally found affecting the carpal bones of the
      hand and should be considered in the differential diagnosis of chronic wrist
      pain. They have characteristic radiographic findings of a cyst with a thin
      sclerotic rim. This case report illustrates an unusual presentation of a cyst in
      the lunate with successful treatment. Standard of care includes curettage and
      bone grafting with minimal recurrence reported.

PMID- 12068231
TI  - Pulsed irrigation of extremity wounds: a simple technique for splashback
      reduction.
AB  - Although blood and body fluid exposures are daily events often assumed to be
      unavoidable by operating room personnel, the potentially lethal consequences of
      blood-borne pathogen transmission demand preventive measures to minimize
      contamination risk. The authors outline a simple technique of extremity
      irrigation that uses a clear plastic isolation drape, pulsed lavage equipment,
      and surgical suction. They have found that this technique allows for thorough
      irrigation of wounds while providing optimal barrier protection.

PMID- 12068233
TI  - Re: Simplifying microvascular head and neck reconstruction.

PMID- 12068235
TI  - Use of AlloDerm for lip reaugmentation.

PMID- 12068236
TI  - Thermal injury to replanted finger caused by infrared rays.

PMID- 12068237
TI  - Gait analysis: a new perspective on sural nerve graft donor site morbidity
      assessment.

PMID- 12068238
TI  - Fetal skin allografts on newborn excisional wounds.

PMID- 12068239
TI  - Deepithelialized double-breasted flap with synovectomy of the elbow: new
      technique for the management of refractory olecranon bursitis.

PMID- 12068240
TI  - Idiopathic scrotal calcinosis.

PMID- 12068241
TI  - Discriminative stimulus effects of ethanol in C57BL/6J and DBA/2J inbred mice.
AB  - BACKGROUND: Two of the most widely used mouse strains for studying the behavioral
      effects of ethanol are C57BL/6J (B6) and DBA/2J (D2) mice. These strains exhibit
      marked differences in behavioral and physiological responses to ethanol. The
      subjective discriminative stimulus effects of ethanol may play a role in ethanol
      abuse, but the discriminative stimulus profile of ethanol has not been compared
      in B6 and D2 mice. Examination of the discriminative stimulus effects of ethanol
      in B6 and D2 mouse strains may enhance our understanding of the relationship
      between the subjective effects of ethanol and other ethanol-induced behavioral
      effects. METHODS: Twelve adult male C57BL/6J mice and 12 male DBA/2J mice were
      trained to discriminate 1.5 g/kg ethanol from saline in daily 15 min, milk
      reinforced operant sessions. After training, ethanol substitution and response
      rate suppression dose response curves were determined for ethanol, midazolam,
      diazepam, pentobarbital, pregnanolone, 4,5,6,7-Tetrahydroisoxazolo[5,4-c]pyridin
      3-ol (THIP), dizocilpine, and morphine. RESULTS: D2 mice learned the ethanol
      discrimination significantly more quickly than did B6 mice. Ethanol, midazolam,
      pregnanolone, and dizocilpine fully substituted for ethanol in both strains.
      Pentobarbital was more potent in producing ethanol-like discriminative stimulus
      effects in D2 than B6 mice. Midazolam and diazepam were significantly more potent
      in suppressing response rates in D2 than B6 mice. Morphine failed to substitute
      for ethanol in either strain, but the ED50 for morphine suppression of responding
      was significantly lower in B6 than D2 mice. CONCLUSIONS: The initial stimulus
      effects of 1.5 g/kg ethanol may be more salient in D2 than B6 mice. This does not
      appear to result from differences in the neurotransmitter systems that mediate
      ethanol's discriminative stimulus effects. In both strains, gamma-aminobutyric
      acid-positive modulators and a noncompetitive NMDA antagonist substituted for
      ethanol. However, strain differences did exist in the potency of gamma
      aminobutyric acid-positive modulators and morphine for suppressing operant
      responding.

PMID- 12068242
TI  - Decreased ethanol preference and consumption in dopamine transporter female knock
      out mice.
AB  - BACKGROUND: It is commonly believed that the mesolimbic dopamine (DA) system
      participates in the etiology of alcoholism. One of the most important regulators
      of DA synaptic transmission is the DA transporter (DAT). We examined the effects
      of the genetic reduction or deletion of DAT on voluntary ethanol consumption and
      ethanol-induced sedation. METHODS: Ethanol preference and consumption were
      assessed in the two-bottle choice paradigm, and the depressant effects of ethanol
      were evaluated by measuring sleep time after acute injection of ethanol. RESULTS:
      The latent period to lose the righting reflex was shorter in both knock-out mice
      (DAT-KO) and heterozygote mice (HET) than in wild-type (WT) mice. No significant
      difference was found among the three genotypes in the ethanol blood concentration
      at the onset of regaining the righting reflex. Females of all genotypes consumed
      more fluid than males of the same genotype. HET and DAT-KO females had increased
      total fluid consumption compared with WT females. DAT-KO males had increased
      fluid consumption compared with WT and HET males. Ethanol preference and
      consumption were not different among male mice of different genotypes. WT and HET
      females demonstrated significantly higher ethanol consumption than males. HET
      female mice did not differ from WT mice in ethanol preference. There was no
      difference between HET and WT mice in the preference for saccharin or quinine
      solutions. DAT-KO females avoided ethanol, and their consumption and preference
      were lower than in WT and HET females, despite markedly increased total intake.
      DAT-KO mice also demonstrated altered taste preference for saccharin and quinine.
      CONCLUSIONS: Partial deletion of DAT results in increased fluid consumption in
      female mice but does not change ethanol preference in either sex. Complete
      deletion of DAT reduces ethanol preference in female mice; this may be due to a
      combination of the pharmacological actions of DAT deletion and alterations in
      fluid consumption and taste discrimination.

PMID- 12068243
TI  - The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity
      (LAS) rats differ in sensitivity to nicotine.
AB  - BACKGROUND: Studies in rodents selectively bred to differ in alcohol sensitivity
      have suggested that nicotine and ethanol sensitivities may cosegregate during
      selective breeding. This suggests that ethanol and nicotine sensitivities may in
      part be genetically correlated. METHODS: Male and female high alcohol sensitivity
      (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were
      tested for nicotine-induced alterations in locomotor activity, body temperature,
      and seizure activity. Plasma and brain levels of nicotine and its primary
      metabolite, cotinine, were measured in these animals, as was the binding of
      [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain
      regions. RESULTS: Both replicate HAS lines were more sensitive to nicotine
      induced locomotor activity depression than the replicate LAS lines. No consistent
      HAS/LAS differences were seen on other measures of nicotine sensitivity; however,
      females were more susceptible to nicotine-induced seizures than males. No HAS/LAS
      differences in nicotine or cotinine levels were seen, nor were differences seen
      in the binding of nicotinic ligands. Females had higher levels of plasma cotinine
      and brain nicotine than males but had lower brain cotinine levels than males.
      CONCLUSIONS: Sensitivity to a specific action of nicotine cosegregates during
      selective breeding for differential sensitivity to a specific action of ethanol.
      The differential sensitivity of the HAS/LAS rats is due to differences in central
      nervous system sensitivity and not to pharmacokinetic differences. The
      differential central nervous system sensitivity cannot be explained by
      differences in the numbers of nicotinic receptors labeled in ligand-binding
      experiments. The apparent genetic correlation between ethanol and nicotine
      sensitivities suggests that common genes modulate, in part, the actions of both
      ethanol and nicotine and may explain the frequent coabuse of these agents.

PMID- 12068244
TI  - Ethanol sensitivity in ATP-gated P2X receptors is subunit dependent.
AB  - BACKGROUND: P2X receptors are ligand-gated cation channels that are gated by
      synaptically released extracellular adenosine 5'-triphosphate (ATP). P2X
      receptors are inhibited by ethanol; however, few investigations have focused on
      ethanol's effects in P2X receptors. Recently, recombinant homomeric P2X4
      receptors were reported to be sensitive to ethanol's inhibitory action, whereas
      recombinant P2X3 receptors were insensitive to ethanol. The two recombinant
      studies were conducted in different expression systems by using different
      techniques; therefore, questions remain. The present study tests the hypothesis
      that ethanol sensitivity in P2X receptors is subunit dependent. METHODS: The
      effects of ethanol (25-200 mM +/- ATP) on rat recombinant homomeric P2X2 and P2X4
      receptors expressed in Xenopus oocytes were tested by using two-electrode voltage
      clamp techniques. RESULTS: Ethanol inhibited EC10 ATP-gated currents
      significantly less in P2X2 versus P2X4 receptors. A second study found that
      ethanol right-shifted the ATP concentration-response curve in P2X2 receptors,
      which significantly increased the EC50 for ATP without altering the Hill slope or
      maximal current response to ATP. These latter characteristics of ethanol action
      in P2X2 receptors agree with previous work in P2X4 receptors. There was no effect
      of ethanol when tested in the absence of ATP. CONCLUSION: The findings are the
      first to show (1) ethanol inhibition of ATP-activated currents on P2X2 receptors,
      (2) differences in ethanol sensitivity between homomeric P2X receptors when
      tested under matched conditions, and (3) evidence that suggests similar
      mechanisms of ethanol action for P2X2 and P2X4 receptors. These findings provide
      the first direct support for the hypothesis that ethanol sensitivity in P2X
      receptors is subunit dependent.

PMID- 12068245
TI  - Alcohol modulation of neuronal nicotinic acetylcholine receptors is alpha subunit
      dependent.
AB  - BACKGROUND: We have previously shown that n-alcohols exert a dual action on the
      alpha4beta2-type neuronal nicotinic acetylcholine (ACh) receptors (AChRs), with
      shorter-chain alcohols potentiating and longer-chain alcohols inhibiting ACh
      induced currents. Ethanol potentiates the current in alpha4beta2 receptors, yet
      it has little or no effect on the alpha3beta2 receptors. Because the alpha4 AChRs
      are present predominantly in the brain, whereas the alpha3 AChRs are present
      predominantly in the peripheral ganglia, the differential action of ethanol on
      the alpha4beta2 and alpha3beta2 AChRs may contribute to its differential effects
      on the brain and the peripheral nervous system. The purpose of this study was to
      characterize the actions of alcohols on an alpha3-containing nicotinic receptor
      and to further understand the mechanism underlying the differential action of
      ethanol on the two receptor subtypes. METHODS: ACh-induced currents were recorded
      from human alpha3beta2 AChRs recombinantly expressed in human embryonic kidney
      tsA201 cells by using the whole-cell patch clamp technique. RESULTS: The ACh
      induced currents in the alpha3beta2 receptors were potentiated by methanol and
      inhibited by longer-chain alcohols. The transition point from potentiation to
      inhibition and the cutoff point were both shifted to shorter alcohols in the
      alpha3beta2 AChR compared with the alpha4beta2 AChR. This explains why ethanol,
      which was at the transition point, has little or no effect on the alpha3beta2
      AChR. CONCLUSIONS: The alpha3beta2 AChRs are insensitive to ethanol because
      ethanol is at the transition point from potentiation to inhibition among n
      alcohols with different carbon-chain lengths. The differential action on the
      alpha4beta2 and alpha3beta2 AChRs may explain the differential action of ethanol
      on the central nervous system.

PMID- 12068246
TI  - Kindling of withdrawal: a study of craving and anxiety after multiple
      detoxifications in alcoholic inpatients.
AB  - BACKGROUND: The increased severity of withdrawal during successive
      detoxifications from alcohol is well documented for seizures, but the importance
      of the number of withdrawal events for other withdrawal symptoms such as anxiety
      and for alcohol craving is not known. Studies in animals are consistent with
      increases in reinforcing properties of alcohol with a greater number of
      withdrawal experiences. Thus, we predicted that patients who had undergone
      multiple detoxifications would show greater desire for alcohol and might
      experience more anxiety compared with patients with fewer detoxifications or
      compared with social drinkers. METHODS: Forty-two alcoholic inpatients were
      divided on the basis of medically supervised detoxifications into HI-med (more
      than two previous detoxifications, n = 6) and LO-med (two or fewer previous
      detoxifications, n = 36) and compared with a group of social drinkers matched for
      age, sex, and verbal IQ (n = 43). An additional analysis was performed by
      dividing the participants into HI-total (n = 22) and LO-total (n = 20) previous
      detoxification groups (three or more and less than three previous
      detoxifications, respectively) by using all previous detoxifications, which
      included unsupervised attempts. Anxiety was measured by Spielberger's State-Trait
      Anxiety Inventory; mood was evaluated by using the Profile of Mood States;
      craving was evaluated with a short version of the Desire for Alcohol
      Questionnaire; and an emotional Stroop test was used that employed positive,
      negative, and alcohol-related words. RESULTS: When the analysis was based on the
      medically supervised detoxifications only, alcoholic participants (HI- and LO
      med) had higher ratings in trait anxiety and in feelings of anger, anxiety,
      depression, and confusion, but also friendliness; had higher craving ratings; and
      made more errors in the alcohol Stroop compared with social drinkers. In
      addition, the number of errors in the emotional Stroop for negative words was
      higher in the group with the higher number of detoxifications. When we analyzed
      the total number of detoxifications, this effect for the emotional Stroop errors
      was no longer seen. Instead, ratings of anger in the Profile of Mood States were
      greater in the HI-total compared with the LO-total detoxification group. These
      effects remained when the correlates alcohol consumption and degree of dependency
      were introduced as covariates, which showed that the effects found are probably
      attributable to the number of withdrawals. CONCLUSIONS: These data suggest that
      for inpatients with short history of alcoholism, the consequences of multiple
      withdrawals may not relate to anxiety or craving.

PMID- 12068247
TI  - The decreased cellular expression of neuropeptide Y protein in rat brain
      structures during ethanol withdrawal after chronic ethanol exposure.
AB  - BACKGROUND: Neuropeptide Y (NPY) has been implicated in the alcohol-drinking
      behaviors of rodents. This study investigated the possible involvement of NPY in
      the neuroadaptational mechanisms to chronic ethanol exposure and its withdrawal.
      METHODS: Male Sprague-Dawley rats were treated either with Lieber-DeCarli ethanol
      diet or control diet for 15 days, and ethanol-fed rats were withdrawn for 0 and
      24 hr. The protein expression of NPY was determined in cortical, hippocampal,
      amygdaloid, striatal, and hypothalamic structures by using the gold
      immunolabeling histochemical procedure. RESULTS: It was found that ethanol
      withdrawal, but not ethanol treatment, produced significant reductions in NPY
      protein levels in (1) layers IV and V of the frontal and parietal cortex, (2)
      layer II of the piriform cortex, (3) the central and medial nuclei of the
      amygdala, and (4) the paraventricular nucleus of the hypothalamus in rat brain.
      Chronic ethanol exposure and its withdrawal had no effect on the NPY protein
      levels in layers II, III, and VI of the frontal and parietal cortex or cingulate
      gyrus, in hippocampal (CA1, CA2, CA3, and dentate gyrus) and striatal (caudate
      putamen and globus pallidus) structures, or in the ventro-medial hypothalamus and
      basolateral amygdala. However, chronic ethanol exposure and its withdrawal
      produced significant reductions in NPY protein levels in the arcuate nucleus of
      the hypothalamus and in layers IV and V of the cingulate gyrus. CONCLUSIONS:
      These results suggest that the decreased protein levels of NPY in the central and
      medial nuclei of the amygdala, as well as in the cortical and hypothalamic
      structures, during ethanol withdrawal may play an important role in the
      neuromechanisms of some ethanol withdrawal symptoms.

PMID- 12068248
TI  - Temporal discrimination learning in abstinent chronic alcoholics.
AB  - BACKGROUND: Converging evidence from varied experimental paradigms has
      demonstrated that the cerebellum is involved in the timing of learned behavior.
      Given the documented neurological changes secondary to chronic alcoholism,
      particularly cerebellar degeneration, the ability of recovered chronic alcoholics
      to learn a temporal discrimination was assessed by using delayed eyeblink
      classical conditioning. METHODS: Twelve abstinent alcoholic participants and 12
      matched control participants were randomly presented 2 clearly discriminable tone
      conditioned stimuli that were individually paired with 2 different interstimulus
      intervals. RESULTS: The data revealed a significant alteration in the abstinent
      alcoholics' peak latency measure at the long interstimulus intervals and an
      overall impairment in their level of acquisition of conditioned responses. No
      group differences in extinction were observed. CONCLUSIONS: It was speculated
      that cerebellar cortical atrophy caused by years of alcohol abuse resulted in the
      peak latency alteration and that atrophy extending into deep cerebellar nuclei
      caused the overall impairment in conditioned response acquisition.

PMID- 12068249
TI  - Role of acetaldehyde in the discriminative stimulus effects of ethanol.
AB  - BACKGROUND: Acetaldehyde has been suggested to mediate some of the effects of
      ethanol. Acetaldehyde can be produced by the enzyme catalase within the brain
      after ethanol administration. The catalase inhibitor 3-amino-1,2,4-triazole (AT)
      reduces the production of acetaldehyde, and AT administration can reduce a number
      of ethanol-induced behavioral effects; this suggests the involvement of
      acetaldehyde in these behaviors. However, a role for acetaldehyde in mediating
      the discriminative stimulus effects of ethanol remains unclear. METHODS: The
      contribution of acetaldehyde to the discriminative stimulus effects of ethanol
      was investigated by use of a two-lever drug discrimination paradigm with food
      reinforcement. Male Long-Evans rats were trained to discriminate water from
      either 1.0 or 2.0 g/kg ethanol. Stimulus substitution tests were conducted with
      ethanol (0-2.5 g/kg by gavage) and acetaldehyde (0-300 mg/kg intraperitoneally).
      A cumulative dose-response procedure was then used to investigate the effects of
      pretreatments with AT (0.5 and 1.0 g/kg intraperitoneally) on ethanol
      discrimination. RESULTS: Acetaldehyde up to doses that decreased response rates
      (300 mg/kg) did not substitute for the discriminative stimulus effects of 1.0 or
      2.0 g/kg ethanol. In addition, AT pretreatment did not affect the dose-response
      curves for ethanol discrimination. CONCLUSIONS: These results show that exogenous
      acetaldehyde administration does not produce discriminative stimulus effects that
      are similar to those of ethanol. Also, pretreatment with the catalase inhibitor
      did not affect the dose-response curve for ethanol discrimination, and this
      suggests that endogenously produced acetaldehyde does not contribute to the
      discriminative stimulus effects of ethanol. Together these results suggest that
      acetaldehyde does not mediate the discriminative stimulus effects of 1.0 to 2.0
      g/kg ethanol.

PMID- 12068250
TI  - Effects of stress and alcohol on subjective state in humans.
AB  - BACKGROUND: There is increasing evidence that stress and hypothalamic-pituitary
      adrenal axis activation interact with drugs of abuse and influence drug-taking
      behaviors. Both studies with laboratory animals and survey data with alcohol
      users suggest that acute or chronic stressful events increase alcohol intake. One
      mechanism for the increase in alcohol intake may be that stress alters the
      subjective effects produced by the drug in ways that enhance the reinforcing
      properties of alcohol. Therefore, in this study we determined whether an acute
      social stressor alters subjective responses to ethanol in humans. The stressor
      was a modified version of the Trier Social Stress Test, an arithmetic task that
      increases cortisol levels. METHODS: Twenty male volunteers participated in two
      laboratory sessions, in which they performed the Trier Social Stress Test on one
      session and no task on the other session, immediately before consuming a beverage
      that contained ethanol (0.8 g/kg in juice) or placebo (juice alone). Eleven
      subjects received ethanol on both sessions, and nine subjects received placebo on
      both sessions. Primary dependent measures were self-report questionnaires of mood
      states. Salivary levels of cortisol were obtained to confirm the effectiveness of
      the stress procedure. RESULTS: Stress alone produced stimulant-like subjective
      effects. In the group who received ethanol, stress increased sedative-like
      effects and decreased stimulant-like effects. CONCLUSIONS: At this relatively
      high dose of ethanol, stress increased sedative effects of alcohol and did not
      increase desire for more alcohol. It is possible that in some individuals, the
      increased sedative effects after stress may increase the likelihood of consuming
      more alcohol. The effects of stress on consumption at this, or lower, doses of
      alcohol remain to be determined.

PMID- 12068252
TI  - Preoperative evaluation of chronic alcoholics assessed for surgery of the upper
      digestive tract.
AB  - BACKGROUND: Alcoholics are at risk of developing major complications in the
      postoperative period. Adequate prophylactic treatment, as well as preoperative
      abstinence, can significantly decrease the rate of complications. However, the
      preoperative diagnosis of alcoholism is difficult to establish. The purpose of
      this study was to assess whether three preoperative visits, an alcohol-related
      questionnaire (CAGE), and the laboratory markers carbohydrate-deficient
      transferrin (CDT) and gamma-glutamyltransferase (GGT) would increase the rate of
      detection of chronic alcoholics. METHODS: The study included the Departments of
      ENT, Facial and Maxillofacial Surgery, and General Surgery of a university
      hospital; 705 male patients were assessed for tumor surgery of the upper
      digestive tract and were allocated to 5 different groups. All patients were seen
      three times, and five different strategies were used to detect chronic
      alcoholics. The gold standard was the diagnosis of alcohol misuse made by an
      experienced (blinded) investigator according to the DSM-III-R. The main outcome
      measurements were the detection rates of the different test strategies. RESULTS:
      By clinical routine alone, only 16% were detected during the first visit and 34%
      after three visits. If the CAGE questionnaire was added, sensitivity increased to
      64%. The further addition of GGT or CDT led to 80 and 85% detections,
      respectively. A combination of all tests had a sensitivity of 91%. CONCLUSIONS:
      To detect more alcoholic patients at risk for major complications, patients
      should be seen more often, and additional diagnostic tools such as the CAGE, CDT,
      and GGT should be used before surgery.

PMID- 12068251
TI  - Biphasic alcohol response differs in heavy versus light drinkers.
AB  - BACKGROUND: Most studies of risk factors for alcohol-related problems have
      focused on biological family history as a primary risk factor. However, other
      factors, such as early-age heavy drinking, are also risk factors for sustained or
      progressive heavy consumption. Little is currently known about the mechanisms
      underlying binge or heavy drinking. METHODS: This study examined the acute
      subjective and objective effects of ethanol in heavy drinkers versus light
      drinkers. Thirty-four subjects participated in this within-subjects study
      consisting of three early-evening testing sessions in which subjects consumed a
      beverage containing either 0.8 or 0.4 g/kg ethanol or placebo. RESULTS: Compared
      with lighter drinkers, heavy drinkers were more sensitive to the positive
      stimulant-like effects of ethanol (p < 0.05), especially during the increasing
      limb of the blood alcohol curve. Heavy drinkers also showed less sedation and
      cortisol response after alcohol than the light drinkers (p < 0.05). CONCLUSIONS:
      The results indicate that young adult binge drinkers show a biphasic alcohol
      response, with heightened sensitivity to stimulant-like alcohol effects and
      greater tolerance to sedative alcohol effects compared with their light-drinking
      counterparts.

PMID- 12068253
TI  - Attenuated heart rate responses to public speaking in individuals with alcohol
      dependence.
AB  - BACKGROUND: Because individuals with alcohol dependence (AD) have shown blunted
      cortisol responses to psychological stress, we assessed whether they also show
      attenuated cardiovascular responses. This study examined the cardiovascular
      responses of people meeting DSM-IV criteria for AD to orthostasis and public
      speaking. METHODS: Heart rate (HR), stroke volume, cardiac output, total
      peripheral resistance, mean arterial pressure, systolic blood pressure, and
      diastolic blood pressure during orthostasis and public speaking were assessed by
      use of impedance cardiography and Dinamap blood pressure monitoring in 20 AD
      subjects abstinent for 21 to 28 days and in 10 age-matched controls. Orthostasis
      consisted of standing, whereas public speaking involved preparing and presenting
      two speeches. Self-reported mood state was also assessed during the tasks.
      RESULTS: AD subjects had significantly lower resting BP compared with controls.
      Cardiovascular responses to orthostasis were similar between groups. AD subjects
      had attenuated HR during public speaking but reported similar anxiety responses
      to controls. CONCLUSIONS: Comparable cardiovascular responses to orthostasis in
      controls and AD subjects suggest intact reflex control of circulation. AD
      subjects had blunted HR responses to public speaking; this is consistent with the
      attenuated cortisol responses observed in this sample and in previous studies.
      This suggests a possible alteration in limbic system regulation of hypothalamic
      and brainstem responses to psychological stress. Cardiovascular responses of AD
      subjects that are inconsistent with subjective accounts of tension and anxiety
      suggest a disconnection between perception of threat and resulting physiologic
      responses in AD subjects.

PMID- 12068254
TI  - Maternal dietary ethanol consumption is associated with hypertriglyceridemia in
      adult rat offspring.
AB  - BACKGROUND: The consumption of significant amounts of alcohol (ethanol, EtOH) may
      markedly increase serum triglyceride levels. This study describes a significant
      increase in fasting serum triglyceride (TG) levels in adult male rats whose
      mothers consumed EtOH. The hypertriglyceridemia occurred although the offspring
      never directly consumed EtOH and had consumed only rat chow for the preceding 14
      months. Furthermore, both male and female adult offspring had an additional,
      significant increase in TG levels if their mothers consumed EtOH and experienced
      stress (restraint) during the pregnancy. METHODS: Harlan-derived Sprague Dawley
      female rats were dosed during pregnancy with EtOH via a liquid diet, and their
      offspring were compared with offspring of mothers who were either fed ad libitum
      or pair-fed the liquid diet without EtOH. At birth, the offspring of EtOH mothers
      exhibited no visible abnormalities except reduced weight, and all offspring were
      surrogate fostered within 48 hr of birth to mothers who had consumed commercial
      rat chow throughout their pregnancy. After weaning, all offspring consumed only
      commercial rat chow, and they were examined over the next 14 months for changes
      in triglyceride homeostasis as a function of maternal alcohol intake. RESULTS:
      Adult male offspring of mothers that consumed EtOH during their pregnancy had
      significant increases in fasting serum triglycerides associated with an increase
      in the very low density lipoprotein serum fraction. Acute administration of
      insulin to the offspring of all maternal dietary groups resulted in a rapid
      clearing of the serum triglycerides, and there were no differences in basal or
      heparin-releasable lipoprotein lipase activity between any of the progeny.
      Castration of the male offspring of EtOH-treated mothers prevented the
      development of elevated TG levels. Administration of testosterone to littermate
      female offspring increased circulating TG levels compared with testosterone
      treated offspring of pair-fed mothers. EtOH-consuming mothers who also underwent
      five periods of restraint-induced stress (approximately 10 min each session)
      produced offspring whose fasting serum TG levels were higher than those whose
      mothers consumed EtOH but experienced no restraint or who experienced restraint
      but no EtOH. Maternal stress significantly reduced lipoprotein lipase activity in
      some offspring treatment groups, but the changes did not correspond to changes in
      the serum TG levels of the offspring. That is, maternal restraint-induced stress
      was associated with a loss of heparin-releasable lipoprotein lipase activity by
      male progeny from pair-fed and EtOH-fed mothers and the female offspring of ad
      libitum-fed and EtOH-fed mothers. CONCLUSIONS: Although serum triglycerides
      increased with age in all offspring, the increase was much more pronounced in the
      progeny of mothers who consumed EtOH during their pregnancy. The
      hypertriglyceridemia was significantly more pronounced in the male offspring and
      in female offspring treated with testosterone. Castration of male offspring
      inhibited the hypertriglyceridemia development, which suggests that male sex
      hormones may play a role in the development of this condition. Maternal EtOH
      consumption coupled with maternal restraint-induced stress significantly
      increased the level of hypertriglyceridemia in both male and female offspring
      compared with offspring whose mothers experienced restraint but no EtOH or EtOH
      with no restraint. If this study models the human condition, the results could
      represent an unrecognized risk factor in a number of adult disease states
      hypothesized to be associated with hypertriglyceridemia, such as cardiovascular
      disease, hypertension, and diabetes.

PMID- 12068255
TI  - Detection and localization of protein-acetaldehyde adducts in rat brain after
      chronic ethanol treatment.
AB  - BACKGROUND: Ethanol is metabolized to acetaldehyde in the cell, which is
      potentially deleterious because it can react with cellular proteins and form
      protein-acetaldehyde adducts, which can interfere with normal cellular function.
      Because the primary site of ethanol action is the brain, the present study was
      carried out to determine whether protein-acetaldehyde adducts are formed in rat
      brain after chronic ethanol administration. METHODS: Rats were treated with
      ethanol for 1 year, and the formation of protein-acetaldehyde adducts was
      examined by immunoblot analysis and localized in brain by immunohistochemical
      analysis by using affinity purified antibody to acetaldehyde-hemocyanin adduct.
      RESULTS: In the brain of rats administered ethanol for up to 1 year, protein
      acetaldehyde adducts were detectable by immunoblot analysis. In brain,
      mitochondria was the primary site of adduct formation, unlike the liver, where
      the major protein-acetaldehyde adduct has been detected in the cytosol.
      Immunohistochemical localization of protein-acetaldehyde adducts in chronic
      ethanol-treated rat brain demonstrated the selective presence of adducts in
      cortical neurons, granule cell layer of dentate gyrus, neurons in the midbrain,
      and granular cell layers of cerebellum. CONCLUSIONS: These results demonstrate
      the significant formation of protein-acetaldehyde adducts in rat brain after
      ethanol ingestion. The modification of mitochondrial proteins in brain by protein
      acetaldehyde adduct formation is significant because mitochondrial dysfunction
      has been implicated in neurodegeneration.

PMID- 12068256
TI  - Epidermal growth factor protects the liver against alcohol-induced injury and
      sensitization to bacterial lipopolysaccharide.
AB  - BACKGROUND: Whereas the role of proinflammatory cytokines in the pathogenesis of
      alcoholic liver disease has been at the forefront of investigation, a possible
      role for anti-inflammatory cytokines in this disease has received little
      attention. This study investigated (1) the hepatic protective effect of an anti
      inflammatory cytokine, epidermal growth factor (EGF), against deleterious effects
      of alcohol and sensitization to bacterial lipopolysaccharide (LPS), and (2) the
      possible mechanisms that underlie such protection. METHODS: Male C57BL/6 mice
      were fed a Lieber-DeCarli liquid diet that contained alcohol or an isocaloric
      replacement for 6 weeks. The animals then were treated daily with human EGF for 7
      days (5 microg/mouse), after which they were injected with either LPS (1 mg/kg of
      body weight) or vehicle and killed 8 hr later. Blood and liver were analyzed for
      plasma aminotransferase activity, liver histology, liver apoptotic nuclei, mRNA
      of several cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta,
      IL-6, and IL-10), apoptotic ligands (TRAIL), cytokine receptors (TNFRp55), pro-
      and antiapoptotic regulators/adaptors (Fas receptor, FasL, FADD, TRADD, RIP, Bak,
      Bax, Bcl-X, Bcl-2 and Bcl-w), and caspase-8. RESULTS: Alcohol increased plasma
      aminotransferase activity and sensitized the liver to the effects of LPS, such as
      polymorphonuclear infiltration, occurrence of necrotic foci and microabscesses,
      and increased apoptosis. These changes were associated with elevated mRNA
      expression of proapoptotic regulators/adaptors. EGF either counteracted or
      markedly blunted most of these effects. EGF did not affect liver mRNA expression
      of TNF-alpha, IL-1beta, IL-6, and IL-10, which suggested that these cytokines
      were not involved in EGF protective effect. EGF protection was mediated by down
      regulation of apoptosis through suppression of proapoptotic gene expression.
      CONCLUSIONS: EGF protects the liver against both alcohol-induced liver damage and
      liver sensitization to bacterial LPS through down-regulation of apoptosis.

PMID- 12068257
TI  - Acquisition and retention of verbal and nonverbal information in children with
      heavy prenatal alcohol exposure.
AB  - BACKGROUND: Memory deficits are reported commonly in children with fetal alcohol
      syndrome. However, little is known about nonverbal memory performance in this
      population. METHODS: The current study examined learning and memory abilities in
      alcohol-exposed children and nonexposed controls. Multiple verbal and nonverbal
      measures were used that incorporated repeated learning trials and delayed recall
      trials. The alcohol-exposed group included children with heavy prenatal alcohol
      exposure with and without fetal alcohol syndrome. Children ranged in age from 8
      to 16 years, and groups were matched on age, sex, ethnicity, and socioeconomic
      status. RESULTS: Children with heavy prenatal alcohol exposure displayed deficits
      in learning and recall of verbal and nonverbal information across all measures.
      On learning trials, they recalled fewer words and displayed a lower rate of
      acquisition. However, when we analyzed delayed verbal recall data after
      controlling for initial verbal learning, group differences were not apparent. The
      same pattern did not occur for nonverbal information; children with prenatal
      alcohol exposure recalled less on delayed recall even when we accounted for
      initial learning. CONCLUSIONS: These data are consistent with previous studies
      that indicate immediate memory deficits but suggest that, at least for verbal
      information, delayed recall deficits in this population are better accounted for
      by deficits in initial learning. Importantly, a different pattern of results was
      demonstrated for verbal versus nonverbal information, which suggests the need for
      additional research in this area.

PMID- 12068258
TI  - Ethanol consumption increases nitric oxide production in rats, and its
      peroxynitrite-mediated toxicity is attenuated by polyenylphosphatidylcholine.
AB  - BACKGROUND: Nitric oxide generally mediates beneficial responses but becomes
      deleterious when coexistence with enhanced superoxide formation leads to the
      synthesis of peroxynitrite, a potent oxidant and nitrating agent. METHODS: To
      study the effects of ethanol and polyenylphosphatidylcholine on nitric oxide
      metabolism and toxicity, 36 rats were pair-fed liquid diets with 36% of energy
      either as ethanol or as additional carbohydrate for 24 days and were killed 90
      min after intragastric feeding. Half received polyenylphosphatidylcholine in the
      diet (3 g/liter), and the other half equivalent amounts of essential fatty acids
      and choline. Nitric oxide was measured by chemiluminescence in arterial blood and
      liver cytosol and as a product of the inducible nitric oxide synthase activity.
      Peroxynitrite formation was assessed by the increase in nitrotyrosine protein
      residues, measured immunochemically. RESULTS: In blood, administration of ethanol
      with or without polyenylphosphatidylcholine doubled nitric oxide levels. In the
      liver, ethanol increased nitric oxide by 52% (p < 0.01), and
      polyenylphosphatidylcholine attenuated this effect. Ethanol consumption increased
      the cytosolic activity of the inducible nitric oxide synthase and induced
      microsomal cytochromes P-450 capable of producing both nitric oxide and
      superoxide. This was associated with an 18% (p < 0.01) increase in nitrotyrosine
      protein residues, products of peroxynitrite toxicity, which occurred
      predominantly in steatotic hepatocytes. Polyenylphosphatidylcholine attenuated
      these changes by decreasing the ethanol effect on both the cytosolic and the
      microsomal activities, in addition to acting as a powerful antioxidant. Acute
      administration of the same ethanol dose increased nitric oxide levels, but did
      not affect nitrotyrosine protein residues. CONCLUSIONS: Chronic, but not acute,
      ethanol administration increases peroxynitrite hepatotoxicity by enhancing
      concomitant production of nitric oxide and superoxide, both of which are
      prevented by polyenylphosphatidylcholine.

PMID- 12068260
TI  - Alcohol advertising and youth.
AB  - This article presents the proceedings of a symposium at the 2001 Research Society
      on Alcoholism meeting in Montreal, Canada. The symposium was organized and
      chaired by Joel W. Grube. The presentations and presenters were (1) Introduction
      and background, by Susan E. Martin; (2) The effect of alcohol ads on youth 15-26
      years old, by Leslie Snyder, Mark Hamilton, Fran Fleming-Milici, and Michael D.
      Slater; (3) A comparison of exposure to alcohol advertising and drinking behavior
      in elementary versus middle school children, by Phyllis L. Ellickson and Rebecca
      L. Collins; (4) USC health and advertising project: assessment study on alcohol
      advertisement memory and exposure, by Alan Stacy; and (5) TV beer and soft drink
      advertising: what young people like and what effects? by Meng-Jinn Chen and Joel
      W. Grube.

PMID- 12068259
TI  - Treating adolescents together or individually? Issues in adolescent substance
      abuse interventions.
AB  - This article summarizes the proceedings of a symposium, chaired by Peter Monti
      and cochaired by Tracy O'Leary, that was presented at the 2001 RSA Meeting in
      Montreal, Quebec. The aim of this symposium was to present data on group- and
      individual-based interventions for adolescent alcohol and substance abuse, with a
      discussion of the implications of research findings bearing on developmental
      considerations when working with adolescents and young adults. Elizabeth J.
      D'Amico, PhD, reviewed recent findings on adolescents' choice of type of
      substance abuse treatment. Jennifer L. Maggs, PhD, presented a developmental
      perspective on this issue. Tracy O'Leary, PhD, presented data on enhancing
      motivational interviewing with the presence of a supportive peer for college
      students cited for alcohol infractions. Mary E. Larimer, PhD, presented 1-year
      follow-up results of the Greeks 2000 Project, a 5-year longitudinal study
      designed to evaluate the efficacy of an alcohol abuse prevention program provided
      to college students who were entering a pledge class (first year) of Greek
      houses. Barbara McCrady, PhD, a noted expert on the treatment of couples for
      substance abuse problems, served as discussant.

PMID- 12068262
TI  - One drink to a lifetime of drinking: temporal structures of drinking patterns.
AB  - This article presents the proceedings of a symposium at the 2001 Research Society
      on Alcoholism Meeting in Montreal, Canada. The cochairs were Paul J. Gruenewald
      and Marcia Russell. The focus of the symposium was on mathematical,
      methodological, and statistical approaches to the assessment of drinking patterns
      from short (daily and monthly) to very long periods (the life course) of time.
      The research presented in the symposium argues that (1) model-based approaches to
      analyzing drinking patterns can provide comprehensive bases for assessing
      drinking risks, (2) data acquisition technologies that track daily drinking over
      long periods of time can illuminate unique features of drinking associated with
      abuse and dependence, and (3) retrospective data can be used to assess life
      course trajectories of drinking associated with chronic problem outcomes. Each of
      the presentations points toward an integrated approach to understanding acute and
      chronic risks related to alcohol use. The presentations were (1) Mathematical
      models of current drinking, by Paul J. Gruenewald and Fred Johnson; (2)
      Mathematical models of drinking problems, by John Light and Rob Lipton; (3)
      Patterns of drinking ascertained from daily data aggregated across 24 months, by
      John Searles; and (4) Cognitive lifetime drinking histories and natural histories
      of drinking, by Marcia Russell, Paul J. Gruenewald, Fred Johnson, Maurizio
      Trevisan, Jo Freudenheim, Paola Muti, Ann Marie Carosella, and Thomas H.
      Nochajski.

PMID- 12068261
TI  - Effects of alcohol and oxidative stress on liver pathology: the role of the
      mitochondrion.
AB  - This article represents the proceedings of a symposium at the 2001 Research
      Society on Alcoholism meeting in Montreal, Canada. The chairs were Alan Cahill
      and Carol C. Cunningham. The presentations were (1) Mitochondrial regulation of
      ethanol-induced hepatocyte apoptosis: possible involvement of proapoptotic Bcl-2
      family protein Bax, by Masayuki Adachi and Hiromasa Ishii; (2) Effects of ethanol
      on mitochondrial reactive oxygen species production and oxidative protein
      modification, by Shannon M. Bailey; (3) Acute ethanol binges elicit widespread
      oxidative mitochondrial DNA damage and depletion: protective effects of
      antioxidants and inhibitors of ethanol metabolism, by Bernard Fromenty; and (4)
      Effects of chronic ethanol consumption upon hepatic mtDNA oxidative modification
      and depletion, by Alan Cahill and Adrian Davies.

PMID- 12068263
TI  - Advancing the expectancy concept via the interplay between theory and research.
AB  - Four papers from a 2001 Research Society on Alcoholism symposium on expectancy
      theory and research are summarized. The symposium contributors describe recent
      advances in expectancy theory and discuss their implications for assessment and
      for understanding the processes of development and change in the behavioral
      domain of alcohol use. First, findings are integrated across the diverse domains
      in which the expectancy concept has been applied. Second, the implications of
      expectancy theory for the measurement of expectancy structure and process are
      examined. Third, research and theory regarding alcohol expectancy development and
      change are presented, with an emphasis on the role of expectancies as mediators
      of known antecedents of drinking. Finally, an experimental procedure for
      investigating the causal role of expectancies is described, together with its
      implications for theory testing and prevention or intervention programming.
      Collectively, the symposium contributions demonstrate the utility of an
      integrated expectancy theory for the generation of innovative research operations
      and new insights regarding behavior development and change. Consistent with the
      notion of consilience, expectancy theory has demonstrated a convergence of
      findings across different levels of analysis, as well as across different
      operations, methods, and research designs.

PMID- 12068264
TI  - Promoting self-change with alcohol abusers: a community-level mail intervention
      based on natural recovery studies.
AB  - BACKGROUND: By using a public health approach to the treatment of alcohol
      problems, this study analyzed the efficacy and cost analysis of two versions of a
      community-level mail intervention to promote self-change among alcohol abusers
      who had never sought help or treatment. METHODS: A total of 825 participants who
      responded to media solicitations were randomly assigned to one of two
      interventions: (a) for bibliotherapy/drinking guidelines (n = 411), they were
      given two pamphlets with information about the effects of alcohol and guidelines
      for low-risk drinking and self-monitoring, and (b) for motivational
      enhancement/personalized feedback (n = 414), personalized advice/feedback was
      provided on the basis of the participants' assessment of their drinking and
      related behaviors. RESULTS: Although both groups exhibited significant reductions
      in drinking from 1 year before to 1 year after intervention, there were no
      significant differences between the two interventions for any variable. This
      suggests that the materials, irrespective of whether they were personalized,
      facilitated the reduction of drinking. Cost analysis revealed that a brief mail
      intervention could reduce drinking at a very low cost per participant (US$46 to
      US$97). CONCLUSIONS: A brief community-level mail intervention for problem
      drinkers who had never sought treatment resulted in sizable reductions in alcohol
      use over the year after the intervention compared with the year before.
      Furthermore, many of those with poorer outcomes engaged in a natural stepped-care
      process by seeking help. These results, coupled with the low cost to deliver the
      intervention, suggest that public health campaigns could have a substantial
      effect on reducing alcohol problems and associated costs as well as getting some
      individuals into treatment. Such an approach would represent a shift from the
      alcohol field's long-standing clinical focus to a broader public health
      perspective.

PMID- 12068266
TI  - [How and how far to investigate ischemic colitis?].

PMID- 12068267
TI  - [New aspects of intestinal bacterial invasion].

PMID- 12068268
TI  - [Non-antibiotic treatments for infectious enterocolitis].

PMID- 12068269
TI  - [New infectious colitis].

PMID- 12068270
TI  - [Update on microscopic colitis].

PMID- 12068271
TI  - [The natural history of colorectal cancer revisited].

PMID- 12068272
TI  - [New histologic prognostic factors in colorectal cancer].

PMID- 12068273
TI  - [Familial forms of colon cancer, familial adenomatous polyposis, hereditary non
      polyposis colorectal cancers].

PMID- 12068274
TI  - [Current debates on rectal cancer].

PMID- 12068275
TI  - [Colorectal cancer screening: facts and questions].

PMID- 12068276
TI  - [Pathophysiology of chronic pancreatitis. Molecular and genetic studies].

PMID- 12068277
TI  - [New causes of chronic pancreatitis].

PMID- 12068278
TI  - [Natural history of alcoholic chronic pancreatitis].

PMID- 12068279
TI  - [Diagnosis of early chronic pancreatitis].

PMID- 12068280
TI  - [Endoscopic management of chronic pancreatitis].

PMID- 12068282
TI  - [The burden of alcohol on public health in France].

PMID- 12068281
TI  - [Practical evaluation of alcohol consumption, classifications and definitions of
      alcoholic behavior].

PMID- 12068283
TI  - [Risky alcohol drinking or problems and brief interventions].

PMID- 12068284
TI  - [Alcohol withdrawal syndrome management. Preventive and curative treatment].

PMID- 12068285
TI  - [Long-term treatment of alcohol dependance].

PMID- 12068286
TI  - [Alcohol and multiple drug abuse].

PMID- 12068287
TI  - Immunoglobulin-free light chains elicit immediate hypersensitivity-like
      responses.
AB  - Immunoglobulin (Ig)-free light chains IgLC are present in serum and their
      production is augmented under pathological conditions such as multiple sclerosis,
      rheumatoid arthritis and neurological disorders. Until now, no
      (patho)physiological function has been ascribed to circulating Ig light chains.
      Here we show that IgLCs can confer mast cell dependent hypersensitivity in mice.
      Antigenic stimulation results in plasma extravasation, cutaneous swelling and
      mast-cell degranulation. We show that IgLCs have a crucial role in development of
      contact sensitivity, which could be completely prevented by a novel IgLC
      antagonist. Although IgE and IgG(1) are central to the induction of immediate
      hypersensitivity reactions, our results show that IgLCs have similar activity.
      IgLCs may therefore be a novel factor in the humoral immune response to antigen
      exposure. Our findings open new avenues in investigating the pathogenesis of
      autoimmune diseases and their treatments.

PMID- 12068288
TI  - HIF-1-induced erythropoietin in the hypoxic retina protects against light-induced
      retinal degeneration.
AB  - Erythropoietin (Epo) is upregulated by hypoxia and provides protection against
      apoptosis of erythroid progenitors in bone marrow and brain neurons. Here we show
      in the adult mouse retina that acute hypoxia dose-dependently stimulates
      expression of Epo, fibroblast growth factor 2 and vascular endothelial growth
      factor via hypoxia-inducible factor-1alpha (HIF-1alpha) stabilization. Hypoxic
      preconditioning protects retinal morphology and function against light-induced
      apoptosis by interfering with caspase-1 activation, a downstream event in the
      intracellular death cascade. In contrast, induction of activator protein-1, an
      early event in the light-stressed retina, is not affected by hypoxia. The Epo
      receptor required for Epo signaling localizes to photoreceptor cells. The
      protective effect of hypoxic preconditioning is mimicked by systemically applied
      Epo that crosses the blood retina barrier and prevents apoptosis even when given
      therapeutically after light insult. Application of Epo may, through the
      inhibition of apoptosis, be beneficial for the treatment of different forms of
      retinal disease.

PMID- 12068289
TI  - Diet-induced insulin resistance in mice lacking adiponectin/ACRP30.
AB  - Here we investigated the biological functions of adiponectin/ACRP30, a fat
      derived hormone, by disrupting the gene that encodes it in mice.
      Adiponectin/ACRP30-knockout (KO) mice showed delayed clearance of free fatty acid
      in plasma, low levels of fatty-acid transport protein 1 (FATP-1) mRNA in muscle,
      high levels of tumor necrosis factor-alpha (TNF-alpha) mRNA in adipose tissue and
      high plasma TNF-alpha concentrations. The KO mice exhibited severe diet-induced
      insulin resistance with reduced insulin-receptor substrate 1 (IRS-1)-associated
      phosphatidylinositol 3 kinase (PI3-kinase) activity in muscle. Viral mediated
      adiponectin/ACRP30 expression in KO mice reversed the reduction of FATP-1 mRNA,
      the increase of adipose TNF-alpha mRNA and the diet-induced insulin resistance.
      In cultured myocytes, TNF-alpha decreased FATP-1 mRNA, IRS-1-associated PI3
      kinase activity and glucose uptake, whereas adiponectin increased these
      parameters. Our results indicate that adiponectin/ACRP30 deficiency and high TNF
      alpha levels in KO mice reduced muscle FATP-1 mRNA and IRS-1-mediated insulin
      signaling, resulting in severe diet-induced insulin resistance.

PMID- 12068290
TI  - Inhibition of gastric inhibitory polypeptide signaling prevents obesity.
AB  - Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is
      primarily induced by absorption of ingested fat. Here we describe a novel pathway
      of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both
      hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with
      insulin resistance. In contrast, mice lacking the GIP receptor (Gipr(-/-)) fed a
      high-fat diet were clearly protected from both the obesity and the insulin
      resistance. Moreover, double-homozygous mice (Gipr(-/-), Lep(ob)/Lep(ob))
      generated by crossbreeding Gipr(-/-) and obese ob/ob (Lep(ob)/Lep(ob)) mice
      gained less weight and had lower adiposity than Lep(ob)/Lep(ob) mice. The Gipr(-/
      ) mice had a lower respiratory quotient and used fat as the preferred energy
      substrate, and were thus resistant to obesity. Therefore, GIP directly links
      overnutrition to obesity and it is a potential target for anti-obesity drugs.

PMID- 12068291
TI  - The crystal structure of IgE Fc reveals an asymmetrically bent conformation.
AB  - The distinguishing structural feature of immunoglobulin E (IgE), the antibody
      responsible for allergic hypersensitivity, is the C epsilon 2 domain pair that
      replaces the hinge region of IgG. The crystal structure of the IgE Fc (constant
      fragment) at a 2.6-A resolution has revealed these domains. They display a
      distinctive, disulfide-linked Ig domain interface and are folded back
      asymmetrically onto the C epsilon 3 and C epsilon 4 domains, which causes an
      acute bend in the IgE molecule. The structure implies that a substantial
      conformational change involving C epsilon 2 must accompany binding to the mast
      cell receptor Fc epsilon RI. This may be the basis of the exceptionally slow
      dissociation rate of the IgE-Fc epsilon RI complex and, thus, of the ability of
      IgE to cause persistent allergic sensitization of mast cells.

PMID- 12068292
TI  - Generation of a complete thymic microenvironment by MTS24(+) thymic epithelial
      cells.
AB  - The epithelial component of the thymic microenvironment is indispensable for the
      generation of T lymphocytes. Although the heterogeneity of this epithelium is
      well documented, little is known about precursor-progeny relationships between
      distinct thymic epithelial lineages. Here we characterized a thymic epithelial
      cell subpopulation identified by the cell surface glycoprotein MTS24. These cells
      contained epithelial progenitor cells that were competent and sufficient to fully
      reconstitute the complex thymic epithelial microenvironment that supported normal
      T cell development.

PMID- 12068293
TI  - G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up
      regulating CXCR4.
AB  - Granulocyte colony-stimulating factor (G-CSF) induced hematopoietic stem cell
      mobilization is widely used for clinical transplantation; however, the mechanism
      is poorly understood. We report here that G-CSF induced a reduction of the
      chemokine stromal cell derived factor 1 (SDF-1) and an increase in its receptor
      CXCR4 in the bone marrow (BM), whereas their protein expression in the blood was
      less affected. The gradual decrease of BM SDF-1, due mostly to its degradation by
      neutrophil elastase, correlated with stem cell mobilization. Elastase inhibition
      reduced both activities. Human and murine stem cell mobilization was inhibited by
      neutralizing CXCR4 or SDF-1 antibodies, demonstrating SDF-1 CXCR4 signaling in
      cell egress. We suggest that manipulation of SDF-1 CXCR4 interactions may be a
      means with which to control the navigation of progenitors between the BM and
      blood to improve the outcome of clinical stem cell transplantation.

PMID- 12068294
TI  - Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from
      bile canalicular membranes.
AB  - The ezrin-radixin-moesin (ERM) family of proteins crosslink actin filaments and
      integral membrane proteins. Radixin (encoded by Rdx) is the dominant ERM protein
      in the liver of wildtype mice and is concentrated at bile canalicular membranes
      (BCMs). Here we show that Rdx(-/-) mice are normal at birth, but their serum
      concentrations of conjugated bilirubin begin to increase gradually around 4
      weeks, and they show mild liver injury after 8 weeks. This phenotype is similar
      to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused
      by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2),
      although this syndrome is not associated with overt liver injury. In wildtype
      mice, Mrp2 concentrates at BCMs to secrete conjugated bilirubin into bile. In the
      BCMs of Rdx(-/-) mice, Mrp2 is decreased compared with other BCM proteins such as
      dipeptidyl peptidase IV (CD26) and P-glycoproteins. In vitro binding studies show
      that radixin associates directly with the carboxy-terminal cytoplasmic domain of
      human MRP2. These findings indicate that radixin is required for secretion of
      conjugated bilirubin through its support of Mrp2 localization at BCMs.

PMID- 12068295
TI  - Mitochondrial transcription factors B1 and B2 activate transcription of human
      mtDNA.
AB  - Characterization of the basic transcription machinery of mammalian mitochondrial
      DNA (mtDNA) is of fundamental biological interest and may also lead to
      therapeutic interventions for human diseases associated with mitochondrial
      dysfunction. Here we report that mitochondrial transcription factors B1 (TFB1M)
      and B2 (TFB2M) are necessary for basal transcription of mammalian mitochondrial
      DNA (mtDNA). Human TFB1M and TFB2M are expressed ubiquitously and can each
      support promoter-specific mtDNA transcription in a pure recombinant in vitro
      system containing mitochondrial RNA polymerase (POLRMT) and mitochondrial
      transcription factor A. Both TFB1M and TFB2M interact directly with POLRMT, but
      TFB2M is at least one order of magnitude more active in promoting transcription
      than TFB1M. Both factors are highly homologous to bacterial rRNA
      dimethyltransferases, which suggests that an RNA-modifying enzyme has been
      recruited during evolution to function as a mitochondrial transcription factor.
      The presence of two proteins that interact with mammalian POLRMT may allow
      flexible regulation of mtDNA gene expression in response to the complex
      physiological demands of mammalian metabolism.

PMID- 12068296
TI  - Truncating mutations of RB1CC1 in human breast cancer.
AB  - The protein RB1CC1 (retinoblastoma 1 (RB1)-inducible coiled-coil 1) has been
      identified as a key regulator of the tumor-suppressor gene RB1 (ref. 1). RB1CC1
      is localized in the nucleus and has been proposed to be a transcription factor
      because of its nuclear localization signal, leucine zipper motif and coiled-coil
      structure. The gene RB1CC1 is localized to a region of chromosome 8q11 (ref. 2)
      containing several loci of putative tumor-suppressor genes; however, its role in
      human cancers remains to be determined. Here we report that 20% (7 of 35) of
      primary breast cancers examined contained mutations in RB1CC1, including nine
      large interstitial deletions predicted to yield markedly truncated RB1CC1
      proteins. Wildtype RB1CC1 and RB1 were absent or significantly less abundant than
      normal in the seven cancers with mutations in RB1CC1, but were abundant in
      cancers without such mutations. In all seven cancers, both RB1CC1 alleles were
      inactivated; two showed compound heterozygous deletions. Thus, RB1CC1 is
      frequently mutated in breast cancer and shows characteristics of a classical
      tumor-suppressor gene.

PMID- 12068297
TI  - Identification of SLC39A4, a gene involved in acrodermatitis enteropathica.
AB  - We have characterized the human gene SLC39A4, which encodes a protein with
      features characteristic of a ZIP zinc transporter. The chromosomal location and
      expression of SLC39A4, together with mutational analysis of eight families
      affected with acrodermatitis enteropathica, suggest that SLC39A4 is centrally
      involved in the pathogenesis of this condition.

PMID- 12068298
TI  - Mutations in SUFU predispose to medulloblastoma.
AB  - The sonic hedgehog (SHH) signaling pathway directs the embryonic development of
      diverse organisms and is disrupted in a variety of malignancies. Pathway
      activation is triggered by binding of hedgehog proteins to the multipass Patched
      1 (PTCH) receptor, which in the absence of hedgehog suppresses the activity of
      the seven-pass membrane protein Smoothened (SMOH). De-repression of SMOH
      culminates in the activation of one or more of the GLI transcription factors that
      regulate the transcription of downstream targets. Individuals with germline
      mutations of the SHH receptor gene PTCH are at high risk of developmental
      anomalies and of basal-cell carcinomas, medulloblastomas and other cancers (a
      pattern consistent with nevoid basal-cell carcinoma syndrome, NBCCS). In keeping
      with the role of PTCH as a tumor-suppressor gene, somatic mutations of this gene
      occur in sporadic basal-cell carcinomas and medulloblastomas. We report here that
      a subset of children with medulloblastoma carry germline and somatic mutations in
      SUFU (encoding the human suppressor of fused) of the SHH pathway, accompanied by
      loss of heterozygosity of the wildtype allele. Several of these mutations encode
      truncated proteins that are unable to export the GLI transcription factor from
      nucleus to cytoplasm, resulting in the activation of SHH signaling. SUFU is a
      newly identified tumor-suppressor gene that predisposes individuals to
      medulloblastoma by modulating the SHH signaling pathway through a newly
      identified mechanism.

PMID- 12068299
TI  - Placental alpha(2)-adrenoceptors control vascular development at the interface
      between mother and embryo.
AB  - A substantial percentage of human pregnancies are lost as spontaneous abortions
      after implantation. This is often caused by an inadequately developed placenta.
      Proper development of the placental vascular system is essential to nutrient and
      gas exchange between mother and developing embryo. Here we show that alpha(2)
      adrenoceptors, which are activated by adrenaline and noradrenaline, are important
      regulators of placental structure and function. Mice with deletions in the genes
      encoding alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors died between
      embryonic days 9.5 and 11.5 from a severe defect in yolk-sac and placenta
      development. In wildtype placentae, alpha(2)-adrenoceptors are abundantly
      expressed in giant cells, which secrete angiogenic factors to initiate
      development of the placental vascular labyrinth. In placentae deficient in
      alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors, the density of fetal blood
      vessels in the labyrinth was markedly lower than normal, leading to death of the
      embryos as a result of reduced oxygen and nutrient supply. Basal phosphorylation
      of the extracellular signal regulated kinases ERK1 and ERK2 was also lower than
      normal, suggesting that activation of the mitogen-activated protein kinase (MAP
      kinase) pathway by alpha(2)-adrenoceptors is required for placenta and yolk-sac
      vascular development. Thus, alpha(2)-adrenoceptors are essential at the placental
      interface between mother and embryo to establish the circulatory system of the
      placenta and thus maintain pregnancy.

PMID- 12068300
TI  - Morphology of Heschl's gyrus reflects enhanced activation in the auditory cortex
      of musicians.
AB  - Using magnetoencephalography (MEG), we compared the processing of sinusoidal
      tones in the auditory cortex of 12 non-musicians, 12 professional musicians and
      13 amateur musicians. We found neurophysiological and anatomical differences
      between groups. In professional musicians as compared to non-musicians, the
      activity evoked in primary auditory cortex 19-30 ms after stimulus onset was 102%
      larger, and the gray matter volume of the anteromedial portion of Heschl's gyrus
      was 130% larger. Both quantities were highly correlated with musical aptitude, as
      measured by psychometric evaluation. These results indicate that both the
      morphology and neurophysiology of Heschl's gyrus have an essential impact on
      musical aptitude.

PMID- 12068301
TI  - Segmenting nonsense: an event-related potential index of perceived onsets in
      continuous speech.
AB  - Speech segmentation, determining where one word ends and the next begins in
      continuous speech, is necessary for auditory language processing. However,
      because there are few direct indices of this fast, automatic process, it has been
      difficult to study. We recorded event-related brain potentials (ERPs) while adult
      humans listened to six pronounceable nonwords presented as continuous speech and
      compared the responses to nonword onsets before and after participants learned
      the nonsense words. In subjects showing the greatest behavioral evidence of word
      learning, word onsets elicited a larger N100 after than before training. Thus
      N100 amplitude indexes speech segmentation even for recently learned words
      without any acoustic segmentation cues. The timing and distribution of these
      results suggest specific processes that may be central to speech segmentation.

PMID- 12068302
TI  - Filtering of neural signals by focused attention in the monkey prefrontal cortex.
AB  - Prefrontal cortex is thought to be important in attention and awareness. Here we
      recorded the activity of prefrontal neurons in monkeys carrying out a focused
      attention task. Having directed attention to one location, monkeys monitored a
      stream of visual objects, awaiting a predefined target. Although neurons rarely
      discriminated between one non-target and another, they commonly discriminated
      between targets and non-targets. From the onset of the visual response, this
      target/non-target discrimination was effectively eliminated when the same objects
      appeared at an unattended location in the opposite visual hemifield. The results
      show that, in prefrontal cortex, filtering of ignored locations is strong, early
      and spatially global. Such filtering may be important in blindness to unattended
      signals--a conspicuous aspect of human selective attention.

PMID- 12068303
TI  - Three-dimensional orientation tuning in macaque area V4.
AB  - Tuning for the orientation of elongated, linear image elements (edges, bars,
      gratings), first discovered by Hubel and Wiesel, is considered a key feature of
      visual processing in the brain. It has been studied extensively in two dimensions
      (2D) using frontoparallel stimuli, but in real life most lines, edges and
      contours are slanted with respect to the viewer. Here we report that neurons in
      macaque area V4, an intermediate stage in the ventral (object-related) pathway of
      visual cortex, were tuned for 3D orientation--that is,for specific slants as well
      as for 2D orientation. The tuning for 3D orientation was consistent across depth
      position (binocular disparity) and position within the 2D classical receptive
      field. The existence of 3D orientation signals in the ventral pathway suggests
      that the brain may use such information to interpret 3D shape.

PMID- 12068304
TI  - Global effects of feature-based attention in human visual cortex.
AB  - The content of visual experience depends on how selective attention is
      distributed in the visual field. We used functional magnetic resonance imaging
      (fMRI) in humans to test whether feature-based attention can globally influence
      visual cortical responses to stimuli outside the attended location. Attention to
      a stimulus feature (color or direction of motion) increased the response of
      cortical visual areas to a spatially distant, ignored stimulus that shared the
      same feature.

PMID- 12068305
TI  - DARPP-32 and regulation of the ethanol sensitivity of NMDA receptors in the
      nucleus accumbens.
AB  - The medium spiny neurons of the nucleus accumbens receive both an excitatory
      glutamatergic input from forebrain and a dopaminergic input from the ventral
      tegmental area. This integration point may constitute a locus whereby the N
      methyl-D-aspartate (NMDA)-subtype of glutamate receptors promotes drug
      reinforcement. Here we investigate how dopaminergic inputs alter the ethanol
      sensitivity of NMDA receptors in rats and mice and report that previous dopamine
      receptor-1 (D1) activation, culminating in dopamine and cAMP-regulated
      phosphoprotein-32 kD (DARPP-32) and NMDA receptor subunit-1 (NR1)-NMDA receptor
      phosphorylation, strongly decreases ethanol inhibition of NMDA responses. The
      regulation of ethanol sensitivity of NMDA receptors by D1 receptors was absent in
      DARPP-32 knockout mice. We propose that DARPP-32 mediated blunting of the
      response to ethanol subsequent to activation of ventral tegmental area
      dopaminergic neurons initiates molecular alterations that influence synaptic
      plasticity in this circuit, thereby promoting the development of ethanol
      reinforcement.

PMID- 12068306
TI  - Cajal body dynamics and association with chromatin are ATP-dependent.
AB  - Cajal bodies (CBs) are nuclear organelles that contain factors required for
      splicing, ribosome biogenesis and transcription. Our previous analysis in living
      cells showed that CBs are dynamic structures. Here, we show that CB mobility is
      described by anomalous diffusion and that bodies alternate between association
      with chromatin and diffusion within the interchromatin space. CB mobility
      increases after ATP depletion and inhibition of transcription, suggesting that
      the association of CB and chromatin requires ATP and active transcription. This
      behaviour is fundamentally different from the ATP-dependent mobility observed for
      chromatin and suggests that a novel mechanism governs CB, and possibly other,
      nuclear body dynamics.

PMID- 12068307
TI  - Nuclear exclusion of Smad2 is a mechanism leading to loss of competence.
AB  - Controlling the duration of a signalling process in development by loss of
      competence is important because too strong an induction can change cell fate. To
      understand some of the mechanisms that underlie loss of competence, we have
      analysed the transduction of transforming growth factor-beta (TGF-beta)
      signalling during mesoderm formation, which is thought to be induced by TGF-beta
      like signalling, in embryos of the frog Xenopus laevis. Here we show that
      gastrula ectoderm has the ability to express mesodermal marker genes in response
      to the TGF-beta signalling molecule activin for many hours, but then loses this
      ability within 1 h for all mesodermal genes tested. This loss of mesodermal
      competence correlates with the inability of Smad2, the principal intracellular
      signal transducer of activin, to accumulate in the nucleus. Mutating three
      phosphorylation sites within Smad2 abrogates the temporal restriction of Smad2 to
      accumulate in the nucleus. Overexpression of this mutant form of Smad2 can
      prolong the competence of endogenous mesodermal genes to respond to activin
      signalling. Thus, restricting the subcellular localization of an intracellular
      signal transducer constitutes a mechanism that leads to loss of mesodermal
      competence. This mechanism operates within less than an hour, and is therefore
      well suited to control an orderly sequence of inductions.

PMID- 12068308
TI  - Mutations of the BRAF gene in human cancer.
AB  - Cancers arise owing to the accumulation of mutations in critical genes that alter
      normal programmes of cell proliferation, differentiation and death. As the first
      stage of a systematic genome-wide screen for these genes, we have prioritized for
      analysis signalling pathways in which at least one gene is mutated in human
      cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to
      growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer.
      The three RAF genes code for cytoplasmic serine/threonine kinases that are
      regulated by binding RAS. Here we report BRAF somatic missense mutations in 66%
      of malignant melanomas and at lower frequency in a wide range of human cancers.
      All mutations are within the kinase domain, with a single substitution (V599E)
      accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are
      transforming in NIH3T3 cells. Furthermore, RAS function is not required for the
      growth of cancer cell lines with the V599E mutation. As BRAF is a
      serine/threonine kinase that is commonly activated by somatic point mutation in
      human cancer, it may provide new therapeutic opportunities in malignant melanoma.

PMID- 12068309
TI  - A large nucleolar U3 ribonucleoprotein required for 18S ribosomal RNA biogenesis.
AB  - Although the U3 small nucleolar RNA (snoRNA), a member of the box C/D class of
      snoRNAs, was identified with the spliceosomal small nuclear RNAs (snRNAs) over 30
      years ago, its function and its associated protein components have remained more
      elusive. The U3 snoRNA is ubiquitous in eukaryotes and is required for nucleolar
      processing of pre-18S ribosomal RNA in all organisms where it has been tested.
      Biochemical and genetic analyses suggest that U3 pre-rRNA base-pairing
      interactions mediate endonucleolytic pre-rRNA cleavages. Here we have purified a
      large ribonucleoprotein (RNP) complex from Saccharomyces cerevisiae that contains
      the U3 snoRNA and 28 proteins. Seventeen new proteins (Utp1 17) and Rrp5 were
      present, as were ten known components. The Utp proteins are nucleolar and
      specifically associated with the U3 snoRNA. Depletion of the Utp proteins impedes
      production of the 18S rRNA, indicating that they are part of the active pre-rRNA
      processing complex. On the basis of its large size (80S; calculated relative
      molecular mass of at least 2,200,000) and function, this complex may correspond
      to the terminal knobs present at the 5' ends of nascent pre-rRNAs. We have termed
      this large RNP the small subunit (SSU) processome.

PMID- 12068310
TI  - Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits
      neurite outgrowth.
AB  - The inhibitory activity associated with myelin is a major obstacle for successful
      axon regeneration in the adult mammalian central nervous system (CNS). In
      addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence
      suggests the existence of additional inhibitors in CNS myelin. We show here that
      a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte
      myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in
      cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory
      activity associated with CNS myelin. To further elucidate the mechanisms that
      mediate this inhibitory activity of OMgp, we screened an expression library and
      identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein.
      Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons
      of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers
      OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important
      inhibitor of neurite outgrowth that acts through NgR and its associated receptor
      complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to
      regenerate after injury in vivo.

PMID- 12068311
TI  - [Intraoperative Lymphatic Mapping by Dye and/or Radioactive Tracer in Early
      Gastric Cancer].

PMID- 12068312
TI  - Torsades de pointes: unanswered questions.
AB  - Torsade de pointes (Tdp) is a polymorphic ventricular tachycardia (VT) in which
      the axis of the QRS complex changes direction after a certain number of complexes
      as if the complex rotated around the baseline. Tdp is usually associated with QT
      prolongation, and dispersion of ventricular repolarlization (DR). Experimental
      models of tdp are usually associated with induction of early after
      depolarizations (EADs). Several aspects of the pathogenesis of tdp are
      incompletely understood. The purpose of this article is to propose the directions
      in research that may increase our current understanding of the factors
      responsible for tdp. The most plausible hypotheses requiring further supporting
      evidence are: 1. The occurrence of tdp requires the presence of DR i.e. tdp does
      not occur in the absence of DR. 2. EADs appear to play an important role as a
      trigger to tdp in the animal models, but more evidence are needed at the clinical
      level. 3. EADs may be responsible for arrhythmias other than tdp. 4. The greater
      incidence of tdp in the females than in tha males may be attributed to
      differences in the duration of the QT interval and different morphology of the ST
      segment and the T-wave. The above gender differences may be caused by the effects
      of gonadal hormones which modulate some of the membrane currents flowing during
      early ventricular repolarization.

PMID- 12068313
TI  - Anti-tumor effect of N-[3,4-dimethoxycinnamoyl]-anthranilic acid (tranilast) on
      experimental pancreatic cancer.
AB  - The anti-tumor effect of N- [3,4-dimethoxycinnamoyl] -anthranilic acid
      (tranilast) was examined in experimental pancreatic cancer. Proliferation of
      PGHAM-1 cells was inhibited by tranilast in a dose-dependent manner, showing a
      significant difference at a concentration of 25 microgram/ml (p<0.05). In colony
      formation, tranilast reduced the number of colonies at a concentration of 25
      microgram/ml (p<0.01). DNA synthesis for 12 hours was attenuated dose-dependently
      and a significant difference was observed at concentrations of greater than 50
      microgram/ml (p<0.05). From cell cycle analysis, a dose-dependent increase in the
      distribution of G0-G1 phase was observed. In the dorsal air sac model, the mean
      angiogenesis indices in PGHAM-1 chambers were 4.17 +/- 0.22 (control group) and
      2.33 +/- 0.84 (treatment group), and in VEGF chambers they were 3.60 +/- 0.67
      (control group) and 1.92 +/- 0.42 (treatment group), In the peritoneal
      dissemination model, the quantity of sanguineous ascites, the number and the size
      of diaphragmatic nodules and the microvessel density (MVD) of the metastatic site
      were reduced by tranilast significantly. In conclusion, the anti-tumor effect of
      tranilast on proliferation and on tumor-angiogenesis was confirmed in
      experimental pancreatic cancer.

PMID- 12068314
TI  - Genome-wide screening of laser capture microdissected gastric signet-ring cell
      carcinomas.
AB  - Gastric signet-ring cell carcinoma comprises a distinct category of gastric
      cancers and has been reported to have poor prognosis. In an attempt to define
      genetic changes involved in the pathogenesis of this lesion in an in vivo state,
      we isolated signet-ring cell carcinoma cells from freshly fixed smears of tumor
      tissues of 7 primary gastric signet-ring cell carcinomas by laser capture
      microdissection and applied comparative genomic hybridization (CGH) to screen for
      DNA sequence copy number changes. Frequent chromosomal gains were detected on 2q,
      5p, 7q, 14q and 20q, each in 6/7 cases, on 9q, 12q, 17q, and 19q, each in 5/7
      cases, and on 18p in 4/7 cases. Frequent losses were observed on 6p and 17p, each
      in 5/7 cases, on 6q, and 21p, each in 4/7 cases, and on 3p, 8p and 8q, each in
      3/7 cases. Losses on 6p have rarely been observed in conventional types of
      gastric carcinomas reported in the literature. These data provide the first
      evidence for the occurrence of specific genomic aberrations in gastric signet
      ring cell carcinomas. Our observation of frequent losses on 6p chromosomal arm
      may provide novel abnormalities of potential significance in gastric signet-ring
      cell carcinomas, suggesting the involvement of genes residing in this region in
      the genesis of the disease.

PMID- 12068315
TI  - Immunohistochemical study of CYP2E1 in hepatocellular carcinoma carcinogenesis:
      examination with newly prepared anti-human CYP2E1 antibody.
AB  - Cytochrome P450 2E1 (CYP2E1) is known as a heme-containing enzyme that produces
      abundant free radicals, and its involvement in carcinogenesis has been suggested
      in several organs in vivo. In this study, to clarify the involvement of CYP2E1 in
      liver cancer and its carcinogenesis process, we investigated the expression of
      CYP2E1 in 42 surgically resected or biopsied specimens of hepatocellular
      carcinomas (HCC) and 26 cases with other liver lesions immunohistochemically
      using a newly prepared anti-human CYP2E1 antibody. When intracellular CYP2E1
      expression was investigated in three different regions of HCC specimens, the
      expression in hepatocytes of the peri-tumor region was the highest (p<0.001)
      compared with those in the tumor and non-peri-tumor regions. Histologically, the
      expression of CYP2E1 in tumor cells tended to decrease as the cells were less
      differentiated (p<0.0001) and was the lowest in poorly differentiated HCC
      (p<0.01). CYP2E1 expression was highest in the pseudo-glandular type and low in
      the thick trabecular and solid types of HCC (p<0.0001). In mature regenerative
      nodules of liver cirrhosis, adenomatous hyperplasia (AH) and atypical adenomatous
      hyperplasia (AAH) to early-HCC, CYP2E1 expression was notably high as compared
      with other legions. CYP2E1 has a strong free radical-producing ability, and the
      cell injury and DNA damages by the free radicals are considered to be involved in
      carcinogenesis. Therefore, our results suggest that the different expression of
      CYP2E1 in hepatocytes may play important roles in the multistep carcinogenic
      process and the histogenesis of hepatocellular carcinoma.

PMID- 12068316
TI  - [Attenuated mRNA induction of molecules associated with neutrophil migration by
      14-membered ring macrolides inhibits bleomycin induced acute lung injury in
      mice].
AB  - BACKGROUND: Although the pathogeneses of interstitial pneumonia are not well
      understood, it has been reported that inflammatory cells, especially neutrophils,
      and their injurious substances play important roles in the progression of
      interstitial pneumonia. Erythromycin and other 14-membered ring macrolides (14
      MRMLs) have been reported to inhibit chronic airway inflammation by mechanisms of
      anti-neutrophil and several other anti-inflammatory activities. The present study
      was undertaken to investigate the effects and mechanisms of 14-MRMLs
      (erythromycin: EM; clarithromycin: CAM; roxithromycin: RXM) on an experimental
      model of bleomycin (BLM) -induced acute lung injury in mice. METHODS: BLM was
      administered intravenously to ICR mice. For the evaluation of early-phase
      inflammation, cell populations in broncho-alveolar lavage fluid (BALF) and
      induction of mRNA of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1)
      and TNF-alpha tested by RT-PCR in lung tissues were examined at 0 to 13 days
      after BLM. These parameters were also compared with those of the control (NS
      alone), 14-MRMLs-untreated (BLM alone) and-pre-treated (BLM+pre 14-MRMLs) groups.
      RESULTS: The number of neutrophils, macrophages, and lymphocytes significantly
      increased in BAL. Neutrophils especially increased with two peaks after BLM
      administration. 14-MRMLs significantly inhibited both peaks of neutrophil. The
      increase in number of macrophages in BALF was significantly attenuated by EM and
      RXM, and slightly attenuated by CAM. Number of lymphocytes in BALF was
      significantly attenuated by EM and CAM, and slightly attenuated by RXM. Changes
      in mRNA expression of E-selectin, P-selectin, ICAM-1, VCAM-1, and TNF-alpha were
      associated with the number of neutrophils migrating into the airspace. 14-MRMLs
      clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate the
      induction of ICAM-1 and TNF-alpha mRNA, but did not inhibit the induction of E
      selectin and P-selectin mRNA. DISCUSSION: These findings show that 14-MRMLs
      clearly attenuated the expression of VCAM-1mRNA, and tended to attenuate the
      induction of ICAM-1 and TNF-alpha mRNA, and subsequently inhibited leucocyte,
      especially neutrophil migration into the airspace during the early phase of BLM
      induced lung injury and finally inhibited lung fibrosis. This might be one potent
      mechanism of the anti-inflammatory effects of 14-MRMLs in BLM-induced acute lung
      injury. The findings suggest that prophylactic administration of 14-MRMLs may be
      clinically efficacious in preventing acute exacerbation of interstitial pneumonia
      and acute lung injury.

PMID- 12068317
TI  - [Chronobiological research on antidepressant drugs: the effect of the
      antidepressant drugs, trazodone and imipramine on the circadian rhythm using
      electroencephalography in healthy volunteers].
AB  - The effects of the antidepressant drugs trazodone and imipramine on the circadian
      rhythm were studied by means of the sleep propensity test (SPT; sleep latency was
      examined by 35-minute EEG records at 09:00, 11:00, 13:00, 15:00, 17:00). The
      subjects were 11 healthy male volunteers (mean age, 23.6 years old). The drugs
      were administered 4 times a day with single blind trials using an inactive
      placebo as a control. The dosages of the drugs were trazodone 50-100 mg/day and
      imipramine 20-40 mg/day. We discussed the circadian rhythm referring to previous
      polysomnograhy (PSG) studies using the same drugs and dosages with most of the
      same subjects. As a result, the mean sleep latency of SPT was the shortest at
      09:00 (p<0.1) with a placebo, at 11:00 (p<0.05) with trazodone and at 13: 00 (not
      significantly) with imipramine administration. These results suggested that
      neither drug affected sleepiness. They affected the circadian rhythm during the
      daytime (=the day rhythm). They delayed the day rhythm. Delay of the day rhythm
      was due to trazodone and have been caused by not only trazodon administration
      itself, but also by the increase of slow-wave sleep obtained in the previous
      night's PSG study. And the day-rhythm delay was due to imipramine and might have
      been caused by not only imipramine administration itself, but also by the
      decrease in the percentage of slow-wave sleep and REM sleep, and an increase in
      REM latency obtained in the previous night's PSG study. Therefore, we concluded
      that neither drug affected the tendency toward sleepiness, but did affect the day
      rhythm in healthy subjects.

PMID- 12068318
TI  - [The influence of complications on rehabilitation of spinal cord injuries:
      economical minus effects and physical disadvantages caused by urinary tract
      infection and decubitus ulcer].
AB  - There are few studies on the many complications that disrupt the rehabilitation
      of patients with cervical cord injuries and their subsequent health-economic
      benefits. I particularly focused on the treatment of urinary tract infection and
      decubitus ulcers because these are very frequently encountered complications in a
      clinical setting. I examined how these complications affect the progress of
      rehabilitation and facilitate a patient's return to society. The subjects
      included ninety-eight cervical cord injury patients with tetraplegia who were
      discharged from the Rehabilitation Center for Severely Disabled Persons from 1995
      to 2000. I retrospectively investigated these ninety-eight subjects regarding
      ninety-six items from clinical records, among which twenty items were selected
      because they are considered to be closely associated with outcome, such as age,
      sex, length of stay, medical expense, urinary tract infection, and decubitus
      ulcer. Moreover, I examined the influence that urinary tract infection and
      decubitus ulcer had on other items. The average length of stay and total medical
      expenses per patient were 1,174.4 +/- 559.9 days and 13,563,128.4 +/- 6,351,078.1
      yen, respectively. Urinary tract infection and decubitus ulcer occurred at a rate
      of 97% in patients with cervical cord injury undergoing chronic stage
      rehabilitation, and these complications caused a two-fold prolongation of the
      length of stay and a three-fold increase in medical expenses compared with
      patients without complications. It is important to fully recognize that these
      complications produce many expenses as well as those for the medical treatment of
      cervical cord injury.

PMID- 12068319
TI  - Extreme left hepatic lobar atrophy in a case with hilar cholangiocarcinoma.
AB  - We describe an unusual case of extreme hepatic left lobar atrophy with hilar
      cholangiocarcinoma. A 67-year-old woman was referred to Nippon Medical School
      with obstructive jaundice. On admission, computed tomography revealed dilated
      intrahepatic bile ducts and a defect in the area drained by the left side of the
      middle hepatic vein. A Spiegel lobe was demonstrated, but the left lobe could not
      be detected to the left side of the gallbladder. Percutaneous transhepatic
      cholangiography was performed and demonstrated obstruction of the intrahepatic
      bile duct at the hepatic hilum. A drainage catheter was left in place.
      Angiography revealed that the left hepatic artery was present, but there was
      narrowing of the left portal vein. A diagnosis of agenesis of the left hepatic
      lobe with hilar cholangiocarcinoma was made. At surgery, the left lobe appeared
      extremely atrophic without atrophy of the Spiegel lobe. The right anterior
      branches of the hepatic artery and portal vein had been invaded by carcinoma, so
      a left trisegmentectomy was performed. Final pathology was advanced hilar
      cholangiocarcinoma with invasion of the hepatic parenchyma, portal vein, and
      nervous system. The left lobe was atrophic without hepatolithiasis. The left
      portal vein was narrow distal to the Spiegel branch. The serum total bilirubin
      concentration was elevated postoperatively, and the patient was treated for
      hepatic failure. The patient died of pneumonia without recurrence 7 months after
      surgery. This rare case of extreme hepatic left lobar atrophy with hilar
      cholangiocarcinoma was successfully treated by left trisegmentectomy.
      Preoperative portal embolization was unnecessary because the left lobe was
      already atrophic.

PMID- 12068320
TI  - A case of chronic expanding hematoma presenting as a huge mass in the pleural
      cavity.
AB  - We report a case of a huge chronic expanding hematoma completely removed by
      surgery. A 71-year-old man was found to have a 3-cm-diameter round nodule in the
      posterior mediastinum seven years previously. He was not administered any
      treatment because he did not have any other serious symptoms. There was nothing
      in his history that could be related to his present condition, such as thoracic
      surgical treatment or tuberculosis. The massive tumor in the left pleural cavity
      grew, compressing the left lung and heart gradually in the past seven years.
      Cytological examination of a needle biopsy specimen showed only erythrocytes with
      a few infiltrating inflammatory cells. Moreover, his preoperative
      histopathological analysis did not reveal any significant findings. Therefore, he
      underwent complete resection of the hematoma including the fibrous capsule and
      left lower lobectomy. Severance of abundant new vascularizations caused massive
      bleeding. The postoperative course was uneventful. There was no recurrence in the
      two years. In cases of gradual growth of a mass without indications of
      malignancy, we should consider the existence of a chronic expanding hematoma even
      in patients without a history of thoracic operation or tuberculosis.

PMID- 12068321
TI  - [A case report of the living-related liver transplantation for fulminant hepatic
      failure].

PMID- 12068322
TI  - [The roll of catheter ablation in the treatment of atrial fibrillation].

PMID- 12068323
TI  - [Surgical treatment of atrial fibrillation].

PMID- 12068324
TI  - [An absence of the collagen type IV alpha5 chain in Alport Syndrome].

PMID- 12068325
TI  - [Mechanical stress for the bone and soft tissues].

PMID- 12068326
TI  - Inhibition of inducible nitric oxide synthase attenuates interleukin-1 beta
      induced vascular hyporeactivity in the rabbit.
AB  - Inhibition of nitric oxide (NO) synthesis has been indicated to improve
      vasopressor-responsiveness and to increase blood pressure in most septic models.
      However, numerous adverse effects of non-selective NO synthase (NOS) inhibition
      have been reported, and the effect of NOS inhibition on vascular responsiveness
      to vasodilators has not been well studied. Using an isometric tension measurement
      system of vascular rings, we evaluated the effects of an inducible NOS (iNOS)
      inhibitor, L-canavanine (L-CAN) and a non-selective NOS inhibitor, NG-nitro-L
      arginine methyl ester (L-NAME) on interleukin-1 beta (IL-1 beta)-induced vascular
      hyporeactivity in the four different rabbit arteries. Pretreatment of IL-1 beta
      inhibited phenylephrine (Phe)-induced vascular constriction in the carotid artery
      (CA, 49% of control), pulmonary artery (PA, 66%), femoral artery (FA, 71%) and in
      the renal artery (RA, 83%). A combination of NOS inhibitors attenuated the
      vascular hyporeactivity to Phe in all arteries. Pretreatment of IL-1 beta also
      inhibited acetylcholine (Ach)-induced vascular relaxation in FA, RA and CA. In
      PA, the rings were inversely constricted after Ach administration. The
      combination of IL-1 beta with L-CAN, but not with L-NAME, attenuated the Ach
      induced vasorelaxation to the control level in all arteries. These data suggest
      that the selective inhibition of iNOS attenuates the direct endothelial damage
      induced by IL-1 beta in vitro.

PMID- 12068327
TI  - Evolution of staged approach for Fontan operation.
AB  - BACKGROUND: During the early development of the Fontan operation, a number of
      physiologic and anatomical limits were proposed as selection criteria, and two
      criteria, pulmonary vascular resistance and ventricular function, have been
      important in predicting surgical outcome. The use of the bidirectional cavo
      pulmonary shunt as a staging procedure performed to control the pulmonary blood
      flow adequately and reduce ventricular volume over load has resulted in marked
      improvements in the early and late Fontan procedure results. METHODS AND RESULTS:
      At our hospital we perform systemic pulmonary shunt or pulmonary artery banding
      in patients if pulmonary blood flow can not be controlled adequately in the
      neonatal period and then perform bidirectional cavo pulmonary shunt six months
      afterwards. During this operation we also performed simultaneous surgical repair
      for pulmonary artery distortion, anomalies of pulmonary venous connection,
      restriction of bulboventricular foramen and atrioventricular valve regurgitation.
      To determine the efficacy of this staged approach in avoiding increases in
      pulmonary vascular resistance and impaired ventricular function, surgical results
      were investigated. From February 1995 to May 2001, eighteen patients with cardiac
      morphology unsuitable for biventricular repair were admitted to our hospital.
      Twenty-six palliative procedures, were performed including seven pulmonary artery
      banding, three systemic pulmonary shunt, thirteen bidirectional cavo pulmonary
      shunt, one original Glenn procedure, four repair of coarctation of the aorta, two
      total anomalous pulmonary venous connection repair, one mitral valve plasty, and
      two patients required Damus-Kaye-Stansel procedure to release restrictive
      bulboventricular foramen. Fifteen patients underwent a modified Fontan operation
      (total cavopulmonary connection) after these palliative procedures. The operative
      mortality rate for these palliative procedures was 3.8% (1/26). The operative
      mortality rate for Fontan operation was 7.1% (1/14). Three patients awaiting the
      Fontan operation were considered good candidates for a final operation and no
      patients in this series were considered unsuitable for Fontan completion.
      CONCLUSION: Our strategy of staged approach for Fontan procedure offers a good
      prognosis.

PMID- 12068328
TI  - Endoscopic scleroligation is a superior new technique for preventing recurrence
      of esophageal varices.
AB  - This study compared a new method, endoscopic scleroligation, intravariceal
      injection sclerotherapy followed by ligation plus extravariceal injection
      sclerotherapy, with ligation plus extravariceal injection sclerotherapy. Fifty
      nine patients with cirrhosis and esophageal varices were treated by endoscopic
      scleroligation (ESL group, n = 28) or ligation plus extravariceal injection
      sclerotherapy (EVL + extraEIS group, n = 31). The demographics and clinical
      characteristics of the two treatment groups were similar, as was the rate of
      complete eradication with initial treatment. However, the 1- and 3-year
      cumulative recurrence rates in the ESL group (3.8% and 22.4%) were very
      significantly lower than those in the EVL + extraEIS group (48.3% and 81.0%) (p <
      0.0001). The overall survival rates in the two groups were similar. In
      conclusion, endoscopic scleroligation is superior to ligation plus extravariceal
      injection sclerotherapy in preventing variceal recurrence. The efficacy of
      intravariceal injection sclerotherapy before ligation is believed to arise from
      the eradication of feeder vessels.

PMID- 12068329
TI  - Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal
      type breast carcinomas.
AB  - Special attention has focused on E-cadherin and the invasiveness of breast
      carcinoma because E-cadherin was suggested to be the major cell adhesion molecule
      in the mammary gland. In the cytoplasm, E-cadherin is linked to beta-catenin and
      alpha-catenin which mediate the connection of the cytoskeleton. In addition, c
      erbB-2 oncoprotein causes disruption of this cell adhesion system through beta
      catenin phosphorylation. We investigated the expression of E-cadherin, alpha
      catenin and c-erbB-2 gene products in 66 invasive ductal carcinomas by immuno
      histochemistry to examine the relation between the E-cadherin mediated cell
      adhesion system and histological subtypes used in Japan as well as histological
      grading. The series included 21 papillotubular carcinomas, 16 solid-tubular
      carcinomas and 29 scirrhous carcinoma. There were 33 cases of grade I, 20 cases
      of grade II and 13 cases of grade III. We defined P&P&N as E-cadherin positive
      and alpha-catenin positive and c-erbB-2 negative cases to evaluate the
      preservation of the E-cadherin mediated cell adhesion system. There were only 13
      cases (19.7%) of P&P&N in total. As for the frequency of E-cadherin/alpha
      catenin/c-erbB-2 expression and P&P&N, no significant difference between
      histological subtypes was found. However, those in the grade I group tended to be
      higher than in the other two grade groups. Regarding the rates of alpha-catenin
      positive cases and P&P&N cases, there were significant differences between the
      grade I group and a combination group consisting of the grade II and grade III
      groups. These results suggest that the E-cadherin-mediated cell adhesion system
      is frequently lost in invasive ductal-type breast cancers by random loss of E
      cadherin/catenins or c-erbB-2 overexpression, and that the preservation of this
      system correlates with well differentiated morphological features.

PMID- 12068330
TI  - [A clinicopathologic study of autopsy cases with myocardial infarction treated
      with coronary intervention (PTCA/Stenting)].
AB  - A clinicopathologic study was made in 28 patients who died after acute myocardial
      infarction (AMI) treated with coronary intervention (CI: Percutaneous
      transluminal coronary angioplasty (PTCA) or Stenting). Nineteen patients received
      PTCA (12 men and 7 women, 42 to 85 years of age, mean 71.4 years), and 9 patients
      received stenting after PTCA (8 men and 1 woman, 49 to 86 years of age, mean 67.7
      years). Hemorrhagic infarction was found in 23 cases. Compared to direct PTCA,
      more severe hemorrhage was found in cases treated with PTCA after intracoronary
      thrombolytic therapy (rescue PTCA: r-PTCA). Also, severe hemorrhage in the
      infarct area was found in cases treated with percutaneous cardiopulmonary support
      (PCPS) after AMI. Hemorrhagic infarction was found even in patients treated with
      CI in the early phase after AMI, and also in some patients who recovered from
      initial heart failure after AMI. Compared to usual ischemic infarct, healing was
      greatly delayed in the hemorrhagic infarct area. We conclude that special care is
      required in the treatment of patients who received CI, because of a high
      possibility of hemorrhage in the infarct area after CI and the delay in healing
      in the hemorrhagic infarction area.

PMID- 12068331
TI  - Burns caused by dilute hydrofluoric acid in the bleach.
AB  - Two male cleaning workers aged 62 (patient 1) and 28-(patient 2) presented with
      red, swollen, aching hands and fingers. At the first interview, the fingers of
      the right hand of both patients were swollen from the proximal interphalangeal
      joint to the tip of the finger. The fingers were red and intensely painful. The
      bleach that both patients used contained 9.5% hydrofluoric acid, and therefore we
      diagnosed their symptoms as those of burns caused by this agent. We
      subcutaneously injected 8.5% calcium gluconate into the affected fingers and
      dressed them with gauze soaked in cooled 0.025% benzethonium chloride. The
      patients did not use gloves at work, neither of them knew that the cleaning fluid
      contained dilute hydrofluoric acid, and they were unaware of the danger of this
      agent. They had not received proper education about the care and handling of
      poisons and deleterious substances such as hydrofluoric acid. The doctors who had
      examined the patients in the emergency ward overlooked the possibility of
      hydrofluoric acid burns, although they suspected chemical burns and confirmed the
      trade name of the cleaning agent. In addition, although the patients presented
      with intense pain, no white areas of coagulation and blistering, or surrounding
      erythemas, which are characteristic symptoms of such burns, were evident. The
      component of the cleaning agent was described on the container label in very
      small print. Had the words "poison" and "hydrogen fluoride" been printed in large
      characters, the examining doctors in the emergency ward would probably not have
      overlooked the presence of hydrofluoric acid, and the patients would perhaps have
      been more careful when using it. Hydrofluoric acid can be easily obtained by
      anyone through the Internet, although general consumers could not obtain
      industrial quantities. Therefore, the number of burn patients who are not
      familiar with hydrofluoric acid may increase in the future.

PMID- 12068332
TI  - International airport and emergency medical care.
AB  - The Nippon Medical School New Tokyo International Airport Clinic (Airport Clinic)
      was opened in 1992 as Japan's first 24-hour international airport clinic. To
      date, it has provided medical services to a total of 117,953 patients. Of these,
      85,545 (72.5%) were airport employees, 28,662 (24.3%) were passengers, and 3,746
      (3.2%) were others. Of the total, non-Japanese patients accounted for 8,485
      (7.2%). In the year to March 31, 2001, the Clinic treated an average of 43.9
      cases per day. The number of emergency patients was 2,969 or 2.3% of the total,
      of whom 500 (0.4%) were non-Japanese. There were 47 deaths, with age ranging from
      14 to 84 (average age 64.0). The ratio of males to females who died was 28:19. Of
      the 47 deaths, 18 were non-Japanese. Pulmonary thromboembolism is considered to
      have played a role in 25 of the deaths. Based on more than 8 years of airport
      clinical experience, we believe that a first-class international airport should
      have excellent medical facilities that can provide quality emergency medical
      services to travelers and disaster victims.

PMID- 12068333
TI  - A dislocation of the inner head in bipolar prosthesis with a self-centering
      system: a case report.
AB  - We present a case of inner head dislocation 11 years after the replacement of a
      bipolar prosthesis with a self-centering system. An 84-year-old woman with
      osteoarthritis of the left hip underwent a replacement of the Bateman UPF-II
      bipolar prosthesis in 1987. She fell off a chair on April 19 1998, and felt a
      sudden sharp pain in the left hip. Roentgenograms revealed that the inner head
      was dislocated from the outer head. Moreover, on June 19, when she stood up from
      the floor, the dislocation recurred. On July 23, a revision surgery was carried
      out. When the outer head was removed from the acetabulum, the bearing insert was
      markedly worn by the impingement of the femoral stem neck. Because there was no
      evidence of loosening of the femoral stem, a cemented replacement of the
      acetabular component was performed. At a 2-year follow-up, she had mild hip pain,
      but had returned fully to daily living. Our review of current published studies
      reveals that most inner head dislocations occurred in osteoarthritic patients.
      Thus, the occurrence of dislocations may be more dependent on patient selection
      than on failure of the bipolar prosthesis itself.

PMID- 12068334
TI  - [Laparoscopic Heller and Dor operation for esophageal achalasia].

PMID- 12068335
TI  - [Relation between Helicobacter pylori and diseases: knowledge for clinician].

PMID- 12068336
TI  - Some answers, some questions.

PMID- 12068337
TI  - To all members.

PMID- 12068338
TI  - Economic evaluation of the MEDENOX trial: a Canadian perspective. Medical
      Patients with Enoxaparin.
AB  - OBJECTIVE: To perform an economic evaluation of the Prophylaxis in Medical
      Patients with Enoxaparin (MEDENOX) trial from a Canadian perspective. METHOD:
      Using a decision tree model, cost effectiveness analysis was carried out to
      compare the costs and consequences of thromboprophylaxis using enoxaparin 40 mg
      with placebo in tertiary and community settings. From a third party payer's
      perspective, the model calculated the expected rate of symptomatic venous
      thromboembolism (VTE), and the total expected cost of prophylaxis and VTE
      management, including inpatient and outpatient treatment, professional fees and
      long term therapy. Data were derived directly from the MEDENOX trial. Costs are
      direct medical costs in year 2000 Canadian dollars. RESULTS: In a tertiary
      setting in which the estimated inpatient to outpatient deep vein thrombosis
      treatment ratio was 10%:90%, the total expected cost per patient was 64 dollars
      in the enoxaparin group and 62 dollars in the placebo group. The expected
      symptomatic VTE rates were 0.8% and 3.1% in the enoxaparin and placebo groups,
      respectively. The incremental cost effectiveness of enoxaparin 40 mg versus
      placebo was 87 dollars/VTE avoided. In a community hospital setting (with a
      50%:50% inpatient to outpatient deep vein thrombosis treatment ratio), the total
      expected cost per patient was 68 dollars in the enoxaparin group compared with 72
      dollars in the placebo group, indicating that prophylaxis with enoxaparin 40 mg
      was cost saving. The model was sensitive to the inpatient to outpatient ratio.
      However, within each setting, the results were not sensitive to changes in key
      variables. CONCLUSION: For patients hospitalized for acute respiratory failure,
      congestive heart failure or acute infectious disease and who are at moderate risk
      of developing VTE, thromboprophylaxis with enoxaparin 40 mg daily is a cost
      effective strategy in both tertiary and community settings.

PMID- 12068340
TI  - Endoscopic management of obstruction due to an acquired bronchial web.
AB  - Bronchial webs are thin, membrane-like diaphragms that may obstruct the airway.
      Several congenital cases have been reported. Though rare, the true incidence of
      these lesions is probably underestimated because many of them are unrecognized.
      The case of a 71-year-old woman with an acquired bronchial web causing right main
      stem bronchus obstruction that went unrecognized for 47 years post-trauma is
      reported. The lesion was successfully treated using rigid bronchoscopy with laser
      therapy, balloon dilation and stent placement. This is the first reported case of
      an acquired bronchial web formation. It is also the first reported case that was
      successfully treated with this technique.

PMID- 12068339
TI  - The addition of salmeterol 50 microg bid to anticholinergic treatment in patients
      with COPD: a randomized, placebo controlled trial. Chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: In the past, the role of long-acting beta(2-) agonists in chronic
      obstructive pulmonary disease (COPD) relative to other agents has been unclear.
      OBJECTIVES: To compare the effect of adding salmeterol (50 microg bid) or placebo
      to concurrent anticholinergic therapy on symptom scores, quality of life,
      prebronchodilator lung function and exacerbations in patients with moderately
      severe COPD. METHODS: This was a double-blind, randomized, parallel-group study
      in patients aged 40 years or older receiving anticholinergic medication. Patients
      were randomly assigned to treatment with placebo (n=207) or salmeterol (n=201)
      via a Diskus/Accuhaler inhaler for 24 weeks. RESULTS: The morning trough
      (prestudy drug) forced expiratory volume in 1 s (FEV(1)) increased significantly
      above baseline levels among the salmeterol-treated patients. Improvement in
      FEV(1) was greater in the salmeterol group than in the placebo group at four
      weeks (difference 0.06 L, P<0.005), eight weeks (0.06 L, P<0.005) and 16 weeks
      (0.05 L, P<0.05) after the start of treatment. There was a nonsignificant trend
      in favour of salmeterol after 24 weeks of treatment (P=0.198). Improvements in
      morning peak flow were significantly greater in the salmeterol group over 24
      weeks (P<0.01). Although symptom scores were numerically higher in the salmeterol
      group than in the placebo group and there was less requirement for rescue
      bronchodilator use, these differences were not statistically significant. In the
      salmeterol group, fewer patients had exacerbations of COPD, and there was a trend
      toward an improved quality of life. The safety profile of the two groups was
      similar. CONCLUSIONS: Salmeterol has a beneficial effect when added to existing
      anticholinergic therapy in patients with COPD. The regular use of salmeterol for
      six months was not associated with worsening of the underlying airflow
      obstruction; rather, there was a tendency for the trough FEV1 to improve above
      the baseline levels over the treatment period.

PMID- 12068341
TI  - Lactic acidosis in asthma: report of two cases and review of the literature.
AB  - Lactic acidosis is commonly associated with states of hypoxia and decreased
      tissue perfusion. Elevated lactic acid levels have also been observed in
      individuals who are not septic and who are normotensive, but who have received
      systemic adrenergic agonist therapy. This report presents two patients with acute
      asthma treated with very large doses of aerosolized and systemic salbutamol, who
      developed lactic acidosis despite normal systemic hemodynamics and adequate
      oxygenation. Lactic acidosis was clinically important because it contributed to
      respiratory failure in one patient, and complicated the assessment and management
      of acute, severe asthma in the other patient.

PMID- 12068343
TI  - Clinical discriminators between acute brain hemorrhage and infarction: a
      practical score for early patient identification.
AB  - New treatments for acute stroke require a rapid triage system, which minimizes
      treatment delays and maximizes selection of eligible patients. Our aim was to
      create a score for assessing the probability of brain hemorrhage among patients
      with acute stroke based upon clinical information. Of 1805 patients in the Stroke
      Data Bank, 1273 had infarction (INF) and 237 had parenchymatous hemorrhage (HEM)
      verified by CT. INF and HEM discriminators were determined by logistic regression
      and used to create a score. ROC curve was used to choose the cut-point for
      predicting HEM (score </= 2), with sensitivity of 76% and specificity of 83%.
      External validation was done using the NOMASS cohort. Although the use of a
      practical score by emergency personnel cannot replace the gold-standard brain
      image differentiation of HEM from INF for thrombolytic therapy, this score can
      help to select patients for stroke trials and pre-hospital treatments, alert CT
      scan technicians, and warn stroke teams of incoming patients to reduce treatment
      delays.

PMID- 12068342
TI  - Thymic carcinoid tumours.
AB  - Carcinoid tumours of the thymus are rare. The case of a 57-year-old asymptomatic
      man with a carcinoid tumour of the thymus, who showed a widened mediastinum by
      chest x-ray, is presented. Fine needle aspiration suggested the diagnosis, which
      was confirmed by biopsy.

PMID- 12068344
TI  - Neurologic complications after heart transplantation.
AB  - OBJECTIVE: Neurologic complications are known as important cause of morbidity and
      mortality in orthotopic heart transplantation. Our aim was to identify the
      frequency and outcome of neurologic complications after heart transplantation in
      a prospective observational study. METHOD: From September 93 to September 99, as
      part of our routine heart transplantation protocol all patients with end-stage
      cardiac failure were evaluated by the same neurologist before and at the time of
      any neurologic event (symptom or complaint) after transplantation. RESULTS: Out
      of 120 candidates evaluated, 62 were successfully transplanted (53 male; median
      age 45.5 years, median follow-up 26.8 months). Fifteen patients (24%) had
      ischemic, 22 (35%) idiopathic, 24 (39%) Chagas' disease and 1 (2%) had congenital
      cardiomyopathy. Neurologic complications occurred in 19 patients (31%): tremor,
      severe headache, transient encephalopathy and seizures related to drug toxicity
      or metabolic changes in 13; peripheral neuropathy in 4; and spinal cord
      compression in two (metastatic prostate cancer and epidural abscess). No
      symptomatic postoperative stroke was observed. CONCLUSIONS: Although frequent,
      neurologic complications were seldom related to persistent neurologic disability
      or death. Most of the complications resulted from immunosuppression, however, CNS
      infection was rare. The absence of symptomatic stroke in our series may be
      related to the lower frequency of ischemic cardiomyopathy.

PMID- 12068346
TI  - CT scan findings in mild head trauma: a series of 2,000 patients.
AB  - The present study describes the cranial computed tomography (CT) scan findings of
      2,000 cases of mild head trauma (HT) in Curitiba, Southern Brazil. The mean age
      of the entire series was 30.8 +/-19 years. The overall male to female ratio was
      2:1. The most common causes of head injury were interpersonal aggression (17.9%),
      falls (17.4%), automobile accidents (16.2%), falls to the ground (13.1%) and
      pedestrian injuries (13 %). Alcohol intoxication was associated with HT in 158
      cases (7.9%). A normal CT scan was seen in 60.75% (1215) and an abnormal CT scan
      in 39.25% (785) of patients. Out of 785 abnormal CT scan, 518(65.9%) lesions were
      related to HT. The most common CT scan HT related findings were: soft tissue
      swelling (8.9 %), skull fractures (4.3 %), intracranial and subgaleal hematomas
      (3.4% and 2.4 %), brain swelling (2 %) and brain contusion (1.2%). Out of 785
      abnormal CT scans, 267 (34.1%) lesions were not related to head trauma.
      Incidental CT scan findings included brain atrophy (5.9%), one calcification
      (5.2%) several calcifications (2.4%) (probably neurocysticercosis in most cases),
      ischemic infarct (1.9%) and leukoaraiosis (1.3%). These findings showed the
      importance of CT scan examination in mild head injuries. Further studies to
      identify mild HT patients at higher risk of significant brain injury are
      warranted in order to optimize its use.

PMID- 12068345
TI  - Glucose utilisation during status epilepticus in an epilepsy model induced by
      pilocarpine: a qualitative study.
AB  - Status epilepticus (SE) is a medical emergency and it is associated to brain
      damage. 2-deoxy-[14C] glucose (2-DG) procedure has been used to measure the
      alterations in the functional activity of the brain induced by various
      pharmacological and toxicological agents. The aim of this study was to determine
      which changes occur in the seizure anatomic substrates during the SE induced by
      pilocarpine (PILO) using [14C]-2 deoxyglucose functional mapping technique.
      Wistar male adult rats were submitted to SE PILO-induced for 6h and received
      [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE.
      The control animals were submitted to all procedures but received saline and not
      pilocarpine. Brain sections were prepared and exposed X-ray film about seven
      days. The optical density of each region was obtained using a solid state digital
      analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE
      rats on the areas corresponding to the hippocampal formation (+50.6%), caudate
      putamen (+30.6%), frontoparietal cortex (+32.2%), amygdala (+31.7%), entorrinal
      cortex (+28.2%), thalamic nucleus (+93.5%), pre-tectal area (+50.1%) and
      substantia nigra (+50.3%) when compared to control. Our results suggest that the
      different activation levels of the distinct structures may be particularly
      important for understanding triggering and spreading mechanisms underlying
      epileptic activity during status epilepticus.

PMID- 12068347
TI  - Fourth ventricle computed tomography indexes: standardisation and characteristics
      in neurocysticercosis.
AB  - OBJECTIVES: to propose standardisation of fourth ventricle dimensions and to
      study its characteristics in neurocysticercosis. METHOD: a control group (CG)
      constituted by 114 individuals with normal CT, and 80 patients with
      neurocysticercosis composed the group with neurocysticercosis (GN). Measures of
      the inner cranial diameter (Cr), fronto-polar distance between both lateral
      ventricles (FP), antero-posterior (AP) and latero-lateral (LL) fourth ventricle
      width based the standardisation of six indexes. RESULTS: AP/Cr, AP/LL and AP/FP
      were the more discriminative indexes, presenting in CG the mean values of 0.063,
      0.267 and 0.582, respectively. The indexes in GN had values statistically higher
      than in CG. From GN, 51 patients had increased indexes values above 2 standard
      deviation of the CG mean. AP/Ll was >/= 1 in 95% of patients with ventricular
      shunting and in 88% with depression. It also occurred in 73% patients with
      satisfactory follow-up and in everybody who died. CONCLUSION: AP/Cr, AP/LL and
      AP/FP may represent fourth ventricle dimensions.

PMID- 12068348
TI  - Taeniasis and cysticercosis prevalence in a small village from Northeastern
      Brazil.
AB  - Although not considered as an endemic region, the Northeast of Brazil has the
      necessary conditions for the development of taeniasis-cysticercosis complex. In a
      previous paper, we demonstrated that Mulungu do Morro municipality, in the State
      of Bahia, has a high seroprevalence to cysticercosis in epileptic patients.
      OBJECTIVE: to determine the prevalence of taeniasis and positive cysticercosis
      serology in the population of Mulungu do Morro. METHOD: blood and stool samples
      were collected from a random sampling of the population, by family. The
      identification of antibodies against T. solium cysticerci was made by EITB and T.
      solium antigens were identified using a polyclonal antibody-capture ELISA.
      RESULTS: the cysticercosis seroprevalence was 1.6% (C.I. = 0.8 to 2.8%) and the
      taeniasis prevalence 4.5% (C.I. = 3.0 to 6.5%). Seropositivity to cysticercosis
      was higher among those who lived in a house of a person testing positive for
      coproantigen, p=0.017. CONCLUSION: our results demonstrate that the taeniasis
      cysticercosis complex is endemic in Mulungu do Morro. We believe that all areas
      in the world with the same socio-economic and sanitary characteristics are likely
      to have high prevalence of this parasite.

PMID- 12068349
TI  - Spinal cord schistosomiasis in children: analysis of seven cases.
AB  - We describe seven cases of children (ages 2 to 14 years) with myeloradiculopathy
      caused by infection with S. mansoni. None of them presented hepatosplenic
      involvement and one presented an intestinal picture. The myeloradicular and
      pseudotumoral forms were observed in four and three patients, respectively.
      Comparing the reports in the literature, we found that the pseudotumoral form is
      more similarly frequent among children than in adults, while the myelitic and
      myeloradicular forms are the most frequent and distributed across all age groups.
      Diagnosis is based on clinical and epidemiological findings in association with
      laboratory tests. The diagnosis was confirmed by the presence of S. mansoni eggs
      in feces (5 cases) and / or the positivity in specific immunological tests (5
      cases) associated with a cerebrospinal fluid inflammatory pattern with presence
      of eosinophils (between 1 and 24%). Magnetic resonance image, although it does
      not enable an etiological diagnosis, helped to confirm the form and spinal cord
      level of the lesion.

PMID- 12068350
TI  - Management of rheumatic chorea: an observational study.
AB  - BACKGROUND: Rheumatic chorea (RC) has recently been linked to an antibody
      mediated immune mechanism. OBJECTIVE/METHOD: To verify if this knowledge
      reflected in management changes we conceived a descriptive study. RESULTS: The
      medical charts of 20 children (13 females) aged 6 to 12 years (mean 8 years),
      diagnosed as RC from June 1996 to June 1999, were reviewed. All patients received
      some medical treatment. Haloperidol was the most prescribed medication (15
      patients - 75 %). Sulpiride, diazepam and valproate were also used as symptomatic
      treatment. Immune-modulating therapy with prednisone was prescribed for seven
      children. The shortest course of chorea (16 days) occurred in a patient treated
      with prednisone. CONCLUSION: Prednisone has been prescribed for rheumatic chorea
      besides the traditional symptomatic approach. A great variety of antichoreic
      drugs are being employed.

PMID- 12068351
TI  - Sotos syndrome (cerebral gigantism): analysis of 8 cases.
AB  - Sotos syndrome or cerebral gigantism is characterized by macrocephaly,
      overgrowth, mental retardation and central nervous system abnormalities.
      Congenital heart defects may be present. We report 8 patients with this syndrome
      and relate their clinical features, neuroimaging and echocardiographic findings.

PMID- 12068352
TI  - Landau-Kleffner syndrome: study of four cases.
AB  - We describe four patients with clinical features of Landau-Kleffner syndrome and
      discuss electroencephalographic features, treatment and prognosis.
      Anticonvulsants and prednisone were used for treatment with good control of
      seizures in all cases and a less effect response in acquired aphasia. Further
      studies are necessary to elucidate the causes and management of this syndrome.

PMID- 12068353
TI  - Eye-hand preference dissociation in obsessive-compulsive disorder and dyslexia.
AB  - Dyslexia may be a development disturbance in which there are alterations in
      visual-spatial and visual-motor processing, while obsessive-compulsive disorder
      (OCD) is a psychiatric disease in which there are alterations in memory,
      executive function, and visual-spatial processing. Our hypothesis is that these
      disturbances may be, at least partially, the result of a crossed eye and hand
      preference. In the present study 16 controls, 20 OCD (DSM-IV criteria) and 13
      dyslexic adults (Brazilian Dyslexia Association criteria) were included. All had
      a neurological examination, the Yale-Brown scale for obsessive-compulsive
      symptoms application and the Zazzo evaluation for laterality, abridged by
      Granjon. Results showed a right hand preference for 100% of controls, 84.6% of
      dyslexics, and 75% of OCD patients and a right eye preference for 73.3% of
      controls, 69.2% of dyslexics, and 35% of OCD patients. The left eye preference
      was significantly higher in OCD when compared with the two other groups (p =
      0.01) and the left hand preference of OCD patients (25%) was also significant
      when compared to Brazilian population (4%) or British population (4.5%). It is
      possible that this crossed preference may be partially the reason for visual
      spatial and constructive disturbances observed in OCD.

PMID- 12068354
TI  - Supraorbital eyebrow approach to skull base lesions.
AB  - We report our experience with a supraorbital eyebrow minicraniotomy. This
      technique is suitable to lesions situated in the region of the anterior fossa,
      suprasellar cisterns, parasellar region and Sylvian fissure. A 50 mm incision in
      the eyebrow and a supraorbital minicraniotomy is performed. Sixteem patients
      harboring different lesions were operated on with good postoperative and cosmetic
      results. We conclude that this approach is safe and useful in selected cases.

PMID- 12068355
TI  - [Anterolateral extension of the lateral suboccipital approach: an anatomical
      study].
AB  - We studied the extensions of the lateral suboccipital approach (LSOA) in seven
      cadaver heads, in the microsurgical laboratory, in order to establish the
      extensions necessary to approach the anterolateral area of the foramen magnum and
      the jugular foramen. The extensions (bone resection) were accomplished in five
      progressive steps: 1) suboccipital retrossigmoid craniectomy (LSOA
      retrocondylar); 2) extending the craniectomy with removal of half the occipital
      condyle (LSOA partial transcondylar); 3) extending the drilling of the occipital
      condyle to open the hypoglossal foramen, followed by removal of the jugular
      tubercle and opening the jugular foramen (LSOA transcondylar-transjugular); 4)
      complete drilling of the occipital condyle (LSOA complete transcondylar); 5) LSOA
      complete transcondylar plus removal of the atlas lateral mass up to the odontoid
      process (ASOL transcondylar-transjugular). We concluded that the extensions of
      LSOA should be adapted to the topography of the lesion: the LSOA retrocondylar
      for the lateral area of the foramen magnum; the LSOA partial transcondylar for
      the anterolateral portion; the LSOA transcondylar-transjugular to reach the
      jugular foramen; the LSOA complete transcondylar for the anterior part, and the
      LSOA complete transcondylar/translateral mass of the atlas for extradural lesions
      anterior to the foramen magnum.

PMID- 12068356
TI  - [Stereologic study of the cerebellar Purkinje cells submitted to alcoholic
      intoxication in Wistar rats].
AB  - BACKGROUND: to analyze the effect of the alcohol on the cells of Purkinje.
      METHOD: Wistar rats received alcoholic solutions orally in different
      concentrations 4%, 12% and 24%. The animals were sacrificed with 4, 8 and 12
      weeks and the cerebella were randomly cut and embedded in paraffin. Sections of 6
      micrometer (H&E) were stereologically analyzed. RESULTS: The differences among
      the density for area and density of surface of the cells of Purkinje of all of
      the experimental groups (E) and the respective controls (C) were significant.
      With 12 weeks the cell of Purkinje volume density decreased among the groups C
      and E in the concentrations of 4% and 12%, but not for the concentration of 24%,
      probably due to smaller liquid ingestion by the animals. CONCLUSION: The alcohol
      has toxic effect on the Purkinje cellular body in the three studied
      concentrations from 4 weeks.

PMID- 12068357
TI  - [Intracranial hemorrhage during pregnancy and puerperium: experience with fifteen
      cases].
AB  - Intracranial hemorrhage due to arteriovenous malformation or intracranial
      aneurysms is a rare but grave complication of pregnancy. We analyse 15 cases.
      Among these, aneurysms ruptures were responsible for the bleeding in 5 instances.
      Arteriovenous malformation was diagnosed in other 6 patients. The maternal and
      fetal mortality was 20% and 33% respectively. Four aneurysm patients were
      operated on before delivery. We conclude that surgical management of the
      aneurysms is associated with lower maternal and fetal mortality than the
      conservative treatment. The management of angiomatous hemorrhage during pregnancy
      remains controversial.

PMID- 12068358
TI  - [Clinical and etiological considerations about the symptomatic epileptic
      syndromes with occipital paroxism blocked when the eyes open].
AB  - The syndrome of idiopathic partial epilepsy with occipital paroxysms in the EEG
      shows a considerable clinical heterogeneity. The present paper investigated the
      significance of electrophysiologic and clinical characteristics in eight patients
      with occipital paroxysms blocked by the eye opening. All patients were submitted
      to radiological exams including brain MRI and/or CT. There was agreement between
      EEG findings and type of seizures in 5 patients and between anatomical
      abnormalities in the MRI or CT and EEG focal abnormalities in 7 patients. Our
      results confirm that the unusual pattern comes from eletrographic multifactors
      origins.

PMID- 12068359
TI  - [Moyamoya and Down syndrome: study conducted by meta-analysis].
AB  - We present a clinic-epidemiological study of two patients and meta-analysis
      (period 1977-2000 ) of the co-morbidity of the Down syndrome (DS) and moyamoya
      syndrome (MMS). Among the 42 patients listed in this survey, meta-analysis
      permitted to find the highest number of publications by researchers from Japan
      and United States, followed by Brazil and Italy; prevalence of cerebrovascular
      disease in suckling and pre school children; first symptomatology was hemiparesis
      (78.6%), speech disorders (26.2%); ischemic infarction (76.2%); recurring
      ischemic episodes (62%); bilateral impairment (83.3%). This analysis led to the
      conclusion that in the clinic-neurological investigation of DS patients with
      acute hemiparesis episodes, MMS should be included as the most probable
      diagnosis.

PMID- 12068360
TI  - [Clinical and laboratory aspects of acute bacterial meningitis in infants].
AB  - OBJECTIVE: to describe clinical and laboratorial characteristics of acute
      bacterial meningitis in infants. METHOD: data from the prospective follow-up of
      infants with acute bacterial meningitis, admitted at the Hospital Couto Maia
      between March and December 1997, were analyzed with specific statistical
      software. RESULTS: acute bacterial meningitis was more prevalent in infants with
      ages varying from 6 months to 1 year. The most frequent etiologic agent was
      Haemophilus influenzae. The global lethality was 25.9% and among the survivors
      39.3% left the hospital with some abnormality in the neurological exam compatible
      with the brain involvement. CONCLUSION: acute bacterial meningitis in infants is
      a high lethality disease that in the majority of cases can be prevented. We
      consider of great relevance the adoption of health prevention strategies in order
      to reduce the incidence of this disease.

PMID- 12068361
TI  - Acute psychotic disorders induced by topiramate: report of two cases.
AB  - We report on two epileptic patients who developed acute psychosis after the use
      of topiramate (TPM). One patient exhibited severe psychomotor agitation,
      heteroaggressiveness, auditory and visual hallucinations as well as severe
      paranoid and mystic delusions. The other patient had psychomotor agitation,
      depersonalization, derealization, severe anxiety and deluded that he was losing
      his memory. Both patients had to be taken to the casualty room. After
      interruption of TPM in one patient and reduction of dose in the other, a full
      remission of the psychotic symptoms was obtained without the need of
      antipsychotic drugs. Clinicians should be aware of the possibility of development
      of acute psychotic symptoms in patients undergoing TPM treatment.

PMID- 12068362
TI  - Hemimasticatory spasm treated with botulinum toxin: case report.
AB  - We describe a female patient with hemimasticatory spasm, a rare movement disorder
      due to dysfunction of the motor trigeminal nerve of unknown origin. This patient
      had an excellent response to botulinum toxin therapy.

PMID- 12068363
TI  - Tetrasomy 15q11-q13 identified by fluorescence in situ hybridization in a patient
      with autistic disorder.
AB  - We report a female child with tetrasomy of the 15q11-q13 chromosomal region, and
      autistic disorder associated with mental retardation, developmental problems and
      behavioral disorders. Combining classical and molecular cytogenetic approaches by
      fluorescence in situ hybridization technique, the karyotype was demonstrated as
      47,XX,+mar.ish der(15)(D15Z1++,D15S11++,GABRB3++,PML-). Duplication of the 15q
      proximal segment represents the most consistent chromosomal abnormality reported
      in association with autism. The contribution of the GABA receptor subunit genes,
      and other genes mapped to this region, to the clinical symptoms of the disease is
      discussed.

PMID- 12068364
TI  - Lumbar disc herniation associated with scoliosis in a 15-year-old girl: case
      report.
AB  - Intervertebral disc herniation is a rare condition in childhood and adolescence,
      although some cases have already been reported in the literature. We present the
      case of a 15 year-old-girl with low back pain and scoliosis. She had no previous
      history of trauma or collagen diseases. MRI showed L4-L5 and L5-S1 disc
      herniations and no further bone and structural changes. After two level
      discectomy, pain ceased and scoliosis improved, without further treatment. Based
      on her evolution and on what has already been reported in literature, we consider
      that scoliosis associated with disc herniation in young patients is most likely
      to be only an anthalgic position, not indicative of further structural changes.

PMID- 12068366
TI  - Esthesioneuroblastoma: case report.
AB  - Esthesioneuroblatoma (ENB) is a rare tumor arising from the olfactory epithelium
      of the nasal vault which frequently invades the cranial base, cranial vault and
      orbit. ENB has a bimodal age distribution between 11 and 20 years and between 51
      and 60 years. ENB accounts for approximately 1 to 5% of intranasal cancers and no
      consensus has been reached regarding treatment of this tumor. We report on a 66
      year old female patient with a Kadish stage C tumor with frontal lobe invasion
      submitted a total craniofacial resection with a combined head neck and
      neurosurgeon team. The purpose of this study is to analyze the natural history,
      treatment and prognosis of this tumor, based on the literature review.

PMID- 12068365
TI  - [Neurosurgical treatment of sphenoidal mucocele by endonasal transseptal
      endoscopic approach: report of two cases].
AB  - Mucoceles are benign, slowly expansive, mucous-filled cystic lesions that arise
      in the paranasal sinuses. They most commonly occur in the frontal and ethmoid
      sinuses and are rarely in the sphenoid sinus. The incidence of sphenoid sinus
      mucoceles is about 1% of paranasal sinus mucoceles. Almost 200 cases of
      sphenoidal and or intraselar mucoceles have been reported since the first
      description by Berg in 1889. Sphenoid sinus mucoceles result from accumulation of
      secretions due to obstruction of the draining sinus osteum. Clinical
      manifestations are dependent on the direction of the expansion toward adjacent
      structures, and are therefore variable. The diagnosis is based on CT and MRI. The
      neurosurgical treatment was marsupialization of the lesion under endoscopic
      vision by transseptal approach. We report two cases of sphenoidal mucoceles.

PMID- 12068367
TI  - [Solitary fibrous tumor of the meninges: case report].
AB  - The solitary fibrous tumor (SFT) is a rare mesenquimal neoplasm, found originally
      in association with the pleura. Recently, SFT was reported in others sites. The
      extension into adjacent structures is not uncommon. The meningeal involvement by
      SFT is rare and there has only twenty-six cases been reported previously in the
      literature. We report a case of a 25 years-old female patient with generalized
      tonic clonic seizures in the last six years. During the neurologic investigation,
      a tumor in the left occipital region of the brain was found. The patient
      underwent an occipital craniotomy with total resection of the tumor. The
      histopathological and immunohistochemical diagnosis was STF. After three years of
      follow-up, the patient remains stable, with a normal neurological exam. There is
      no sign of tumor recidive in the postoperative cranial tomography. We will
      briefly review the literature about STF.

PMID- 12068368
TI  - [Thalamic intracerebral schwannoma: case report].
AB  - The intracranial schwannomas cover about 8% of all the brain tumors, although,
      those localized inside the encephalic parenchyma are rare only 55 cases being
      reported in the literature. The histopathologic diagnosis is based on the
      cellular type and arrangement common to the nervous sheath tumors, the
      immunohistochemical findings (GFAP, S-100 protein, EMA) and electronmicroscopic
      findings as well. The clinical presentation related to the intraparenchimatous
      schwannoma is variable, depending on its localization, the image diagnosis does
      not show any typical aspect. The surgical treatment is curative once a complete
      extirpation is obtained. These tumors are benign but one case reported presented
      malignant signs. We present a patient that had a thalamic schwannoma with
      histological confirmation. We found no case with this localization in the
      literature.

PMID- 12068369
TI  - [Post-traumatic brain injury behavioural sequelae: the man who lost his charm].
AB  - We portray a case of traumatic brain injury followed by symptoms of disexecutive
      or frontal lobe syndrome: apathy, lack of pragmatism and loss of previous
      abilities, specially those concerning social interaction - in particular with
      opposite sex - resulting in impairment of his characteristic charm. The results
      of the neuropsychological examination included retrieval anemic deficits with
      normal recognition, impaired motor dexterity and cognitive flexibility in the
      presence of normal intelligence. The cognitive-behavioural symptomatology
      contrasted with a normal neurologic examination.

PMID- 12068370
TI  - [Autism, bipolar disorder and mental retardation in a male adolescent with
      congenital rubella: case report].
AB  - We describe an autistic male adolescent with congenital rubella who has developed
      bipolar disorder, discussing possible diagnostic and therapeutic implications.

PMID- 12068371
TI  - [The importance of interdisciplinary staff in the diagnosis of developmental
      dyslexia: case report].
AB  - We describe the work of the interdisciplinary staff of FCM/UNICAMP for the
      diagnosis of developmental dyslexia, evaluating a 9 years old boy from the second
      year of a first grade public school. The procedure consisted of four stages: 1)
      Interview with the mother (anamnesis); 2) neuropsychological evaluation; 3)
      specific evaluation for reading and writing skills; 4) complementary exams. The
      results revealed that the child presented normal intelligence, normal auditory
      and visual function but difficulties in reading specific test, in auditory short
      term memory (specially in auditory sequences), and in phonological conscience, as
      well as slowness, lack of concentration, slight neurological signs and
      hypoperfusion of the mesial portion of the temporal lobe. These data suggest that
      the child has developmental dyslexia of mixed type, requiring psychopedagogic
      follow-up.

PMID- 12068372
TI  - [History of neurosurgery in Rio de Janeiro].
AB  - The professional life of the pioneers of neurological surgery in Rio de Janeiro
      is presented.

PMID- 12068373
TI  - Atypical 5' splice sites cause CFTR exon 9 to be vulnerable to skipping.
AB  - The molecular basis of the skipping of constitutive exons in many messenger RNAs
      is not fully understood. A well-studied example is exon 9 of the human cystic
      fibrosis transmembrane conductance regulator gene (CFTR), in which an abbreviated
      polypyrimidine tract between the branch point A and the 3' splice site is
      associated with increased exon skipping and disease. However, many exons, both in
      CFTR and in other genes and have short polypyrimidine tracts in their 3' splice
      sites, yet they are not skipped. Inspection of the 5' splice sites immediately up
      and downstream of exon 9 revealed deviations from consensus sequence, so we
      hypothesized that this exon may be inherently vulnerable to skipping. To test
      this idea, we constructed a CFTR minigene and replicated exon 9 skipping
      associated with the length of the polypyrimidine tract upstream of exon 9. We
      then mutated the flanking 5' splice sites and determined the effect on exon
      skipping. Conversion of the upstream 5' splice site to consensus by replacing a
      pyrimidine at position +3 with a purine resulted in increased exon skipping. In
      contrast, conversion of the downstream 5' splice site to consensus by insertion
      of an adenine at position +4 resulted in a substantial reduction in exon 9
      skipping, regardless of whether the upstream 5' splice site was consensus or not.
      These results suggested that the native downstream 5' splice site plays an
      important role in CFTR exon 9 skipping, a hypothesis that was supported by data
      from sheep and mouse genomes. Although CFTR exon 9 in sheep is preceded by a long
      polypyrimidine tract (Y(14)), it skips exon 9 in vivo and has a nonconsensus
      downstream 5' splice site identical to that in humans. On the other hand, CFTR
      exon 9 in mice is preceded by a short polypyrimidine tract (Y(5)) but is not
      skipped in vivo. Its downstream 5' splice site differs from that in humans by a 2
      nt insertion, which, when introduced into the human CFTR minigene, abolished exon
      9 skipping. Taken together, these observations place renewed emphasis on
      deviations at 5' splice sites in nucleotides other than the invariant GT,
      particularly when such changes are found in conjunction with other altered
      splicing sequences, such as a shortened polypyrimidine tract. Thus, careful
      inspection of entire 5' splice sites may identify constitutive exons that are
      vulnerable to skipping.

PMID- 12068374
TI  - Premature termination mutations in FBN1: distinct effects on differential allelic
      expression and on protein and clinical phenotypes.
AB  - Marfan syndrome (MFS) and other type 1 fibrillinopathies result from mutations in
      the FBN1 gene, which encodes the connective-tissue microfibrillar protein
      fibrillin 1. Attempts at correlating genotype with phenotype have suggested
      considerable heterogeneity. To define the subtype of fibrillinopathy caused by
      premature termination codon (PTC) mutations, we integrate genotype information
      and mRNA expression levels with clinical and biochemical phenotypes. By screening
      the entire FBN1 gene for mutations, we identified 34 probands with PTC mutations.
      With the exception of two recurrent mutations, these nonsense and frameshift
      mutations are unique and span the entire FBN1 gene, from IVS2 to IVS63. Allele
      specific reverse-transcriptase polymerase chain reaction analyses revealed
      differential allelic expression in all studied samples, with variable reduction
      of the mutant transcript. Fibrillin protein synthesis and deposition into the
      extracellular matrix were studied by pulse-chase analysis of cultured
      fibroblasts. In the majority of PTC samples, synthesis of normal-sized fibrillin
      protein was approximately 50% of control levels, but matrix deposition was
      disproportionately decreased. Probands and mutation-positive relatives were
      clinically evaluated by means of a standardized protocol. Only 71% (22/31) of
      probands and 58% (14/24) of the mutation-positive family members met current
      clinical diagnostic criteria for MFS. When compared with our previously reported
      study group of 44 individuals with FBN1 cysteine substitutions, the PTC group
      showed statistically significant differences in the frequency of individual
      signs, especially in the ocular manifestations. Whereas large-joint hypermobility
      was more common, lens dislocation and retinal detachment were distinctly less
      common in the PTC group. We conclude that PTC mutations have a major impact on
      the pathogenesis of type 1 fibrillinopathies and convey a distinct biochemical,
      clinical, and prognostic profile.

PMID- 12068375
TI  - Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of
      the MTR gene, genotype diversity, and recognition of a common mutation, P1173L.
AB  - Mutations in the MTR gene, which encodes methionine synthase on human chromosome
      1p43, result in the methylcobalamin deficiency G (cblG) disorder, which is
      characterized by homocystinuria, hyperhomocysteinemia, and hypomethioninemia. To
      investigate the molecular basis of the disorder, we have characterized the
      structure of the MTR gene, thereby identifying exon-intron boundaries. This
      enabled amplification of each of the 33 exons of the gene, from genomic DNA from
      a panel of 21 patients with cblG. Thirteen novel mutations were identified. These
      included five deletions (c.12-13delGC, c.381delA, c.2101delT, c.2669-2670delTG,
      and c.2796-2800delAAGTC) and two nonsense mutations (R585X and E1204X) that would
      result in synthesis of truncated proteins that lack portions critical for enzyme
      function. One mutation was identified that resulted in conversion of A to C of
      the invariant A of the 3' splice site of intron 9. Five missense mutations
      (A410P, S437Y, S450H, H595P, and I804T) were identified. The latter mutations, as
      well as the splice-site mutation, were not detected in a panel of 50 anonymous
      DNA samples, suggesting that these sequence changes are not polymorphisms present
      in the general population. In addition, a previously described missense mutation,
      P1173L, was detected in 16 patients in an expanded panel of 24 patients with
      cblG. Analysis of haplotypes constructed using sequence polymorphisms identified
      within the MTR gene demonstrated that this mutation, a C-->T transition in a CpG
      island, has occurred on at least two separate genetic backgrounds.

PMID- 12068376
TI  - Skewed X-chromosome inactivation is a common feature of X-linked mental
      retardation disorders.
AB  - Some deleterious X-linked mutations may result in a growth disadvantage for those
      cells in which the mutation, when on the active X chromosome, affects cell
      proliferation or viability. To explore the relationship between skewed X
      chromosome inactivation and X-linked mental retardation (XLMR) disorders, we used
      the androgen receptor X-inactivation assay to determine X-inactivation patterns
      in 155 female subjects from 24 families segregating 20 distinct XLMR disorders.
      Among XLMR carriers, approximately 50% demonstrate markedly skewed X inactivation
      (i.e., patterns > or =80:20), compared with only approximately 10% of female
      control subjects (P<.001). Thus, skewed X inactivation is a relatively common
      feature of XLMR disorders. Of the 20 distinct XLMR disorders, 4 demonstrate a
      strong association with skewed X inactivation, since all carriers of these
      mutations demonstrate X-inactivation patterns > or =80:20. The XLMR mutations are
      present on the preferentially inactive X chromosome in all 20 informative female
      subjects from these families, indicating that skewing is due to selection against
      those cells in which the XLMR mutation is on the active X chromosome.

PMID- 12068377
TI  - Refined mapping of suggestive linkage to renal function in African Americans: the
      HyperGEN study.

PMID- 12068378
TI  - Mode of inheritance and susceptibility locus for restless legs syndrome, on
      chromosome 12q.

PMID- 12068381
TI  - New applications of cancer immunotherapy.

PMID- 12068382
TI  - Immunologic mechanisms of antitumor activity.
AB  - The growth and metastatic spread of tumors, to a large extent, depends on their
      capacity to evade host immune surveillance and overcome host defenses. All tumors
      express antigens that are recognized to a variable extent by the immune system,
      but in many cases an inadequate immune response is elicited because of partial
      antigen masking or ineffective activation of effector cells. Tumor antigens
      presented in the context of major histocompatability antigen (MHC) class I
      complexes on either the tumor cell itself or on antigen-presenting cells are
      capable of inducing tumor-specific cytotoxic T lymphocytes. The presence of
      costimulatory molecules, such as B7-1 and B7-2, on antigen-presenting cells and
      the secretion of IL-2 promote the differentiation of recruited CD8+ lymphocytes
      into cytotoxic T lymphocytes. Tumor escape from immune effectors is most often
      caused by weak immunogenicity of tumor antigens, antigen masking, or overall
      immunosuppression, a characteristic of advanced cancer. Failure of antigen
      processing or binding to MHC molecules, inadequate or low-affinity binding of MHC
      complexes to T-cell receptors, or inadequate expression of costimulatory adhesion
      molecules in conjunction with the antigen-presenting MHC complex may all lead to
      poor immunogenicity of tumor-associated peptides and impaired antitumor response.
      Therapeutic interventions to augment tumor antigenicity include vaccination with
      immunogenic peptides, administration of in vitro expanded and activated immune
      effector cells, in vivo effector cell expansion with cytokine therapies, or
      genetic modification of either immune effectors or tumor cells with cytokine
      genes or genes encoding costimulatory molecules to effectively activate the
      immune response.

PMID- 12068383
TI  - Interleukin-2: clinical applications.
AB  - Interleukin-2 (IL-2) is a promising immunotherapeutic agent for the treatment of
      metastatic melanoma, acute myelogenous leukemia, and metastatic renal cell
      carcinoma. While high-dose IL-2 regimens have shown clinical benefit in the
      treatment of melanoma and renal cell carcinoma, serious dose-limiting toxicities
      have limited their clinical use in a broader group of patients. Low-dose IL-2
      therapy has produced disappointing clinical response rates in melanoma. While the
      response rates to low-dose IL-2 have been better in renal cell carcinoma, the
      quality of these responses relative to those seen with high-dose IL-2 therapy
      remains a concern. The addition of IL-2 to chemotherapeutic regimens
      (biochemotherapy) has been associated with overall response rates of up to 60% in
      patients with metastatic melanoma, but this has yet to be translated into a
      confirmed improvement in survival. It remains to be determined whether further
      modifications of IL-2-based regimens or the addition of newer agents to IL-2 will
      produce better tumor response and survival.

PMID- 12068384
TI  - Cancer immunotherapy: the interferon-alpha experience.
AB  - Interferons are agents with antiviral, antiproliferative, and immunomodulatory
      properties. Interferon-alfa (IFN-alpha) is used in the treatment of hematologic
      malignancies and solid tumors. IFN-alpha has shown antitumor and antiviral
      efficacy that are not correlated, one with another. Approval by the US Food and
      Drug Administration was granted early for the treatment of patients with hairy
      cell leukemia, acquired immune deficiency syndrome-related Kaposi's sarcoma, and
      condylomata acuminata. Although IFNs are effective as single agents in certain
      clinical pathologic entities, increasing experience with these cytokines suggests
      that their greatest therapeutic potential may be realized in combination with
      other biological response modifiers, cytotoxics, or antiviral agents. For
      example, trials combining IFN-alpha with 5-fluorouracil to treat colorectal
      carcinoma or IFN-alpha with zidovudine to treat acquired immune deficiency
      disorder showed increased efficacy over IFN-alpha alone. While IFN-alpha appears
      to be moderately effective in certain diseases, the flu-like syndrome associated
      with its use is a major limiting factor for its clinical application. Further
      studies are needed to determine the underlying mechanism of action for IFNs and
      the most effective combinations and appropriate preclinical models, or
      intermediate endpoints that will then facilitate the rational use of this agent
      in combinations based on the mechanisms of action of IFN-alpha.

PMID- 12068385
TI  - Cancer immunotherapy with natural killer cells.
AB  - Natural killer (NK) cells were first identified for their ability to kill tumor
      cells of different origins. They were subsequently found to be able to kill some
      normal cells, especially those infected by certain viruses. Natural killer cells
      are a distinct lymphocytic population, with the morphology of large granular
      lymphocytes, and they lack surface Ig or T-cell markers. Natural killer
      cytotoxicity is enhanced in vitro in the presence of cytokines such as
      interleukin-2 and interferon-alpha. However, when used in immunotherapy, these
      cytokines have not consistently augmented NK activity or shown antitumor effects.
      One explanation for this divergence is that NK cell activity is suppressed in
      tumor tissues by various factors, including reactive oxygen species produced by
      infiltrating monocytes and macrophages. Agents that inhibit the generation of
      reactive oxygen species, such as histamine, may abrogate the suppression exerted
      on NK cells by monocytes/macrophages, therefore offering potential therapeutic
      benefit as immunoadjuvants.

PMID- 12068386
TI  - Histamine as an adjunct to immunotherapy.
AB  - Interleukin-2 and interferon-alpha have been used as therapeutic options in the
      treatment of certain malignancies such as metastatic malignant melanoma, acute
      myelogenous leukemia, and renal cell carcinoma. However, the outcome with these
      agents has been less than optimal. While experiments in vitro would lead one to
      believe that these agents would be useful therapeutic alternatives, the situation
      in vivo is confounded by the fact that the microenvironments of the tumor and
      surrounding tissue are infiltrated with monocytes and macrophages, which suppress
      the cytotoxic activity of T cells and natural killer cells. The mechanism by
      which this occurs is through the generation of reactive oxygen species that are
      responsible for apoptosis by both T cells and natural killer cells. Histamine
      abrogates this suppression, thus restoring the cytotoxicity of these cells.
      Therefore, the addition of histamine to regimens containing cytokines is expected
      to optimize cytokine therapy. Clinical trials with these regimens are under way
      in the treatment of metastatic malignant melanoma, acute myelogenous leukemia,
      and renal cell carcinoma. Results published thus far indicate that the addition
      of histamine to cytokine therapy is both safe and efficacious in the treatment of
      these diseases.

PMID- 12068387
TI  - Histamine in cancer immunotherapy: a preclinical background.
AB  - Natural killer (NK) cells and T cells are the primary targets of interleukin-2
      (IL-2) and other cytokines used in cancer immunotherapy. However, these
      tumoricidal lymphocytes are frequently dysfunctional or apoptotic when residing
      within melanomas and other solid cancers. This phenomenon--tumor-induced
      immunosuppression--is poorly understood and conceivably limits the efficiency of
      strategies aiming at activating lymphocyte-mediated antitumor immunity. Recent
      studies imply that reactive oxygen species (oxygen radicals), produced by tumor
      infiltrating monocyte/macrophages, may contribute to the state of lymphocyte
      inhibition in neoplastic tissue. Histamine, acting via H2-type histamine
      receptors on monocyte/macrophages, suppresses the activity of a key enzyme in
      oxygen radical formation, the NADPH oxidase. By this mechanism, histamine
      protects NK cells and T cells against oxygen radical-induced dysfunction and
      apoptosis, and also maintains their activation by IL-2 and other lymphocyte
      activators. In this review, these properties of histamine are discussed in
      relation to the current use of histamine as an adjunct to IL-2 in metastatic
      melanoma and other malignant diseases.

PMID- 12068388
TI  - Therapeutic options in the management of renal cell carcinoma.
AB  - Approximately 31,000 new cases of renal cell carcinoma (RCC) are diagnosed in the
      United States each year and 30% to 40% of these will eventually become metastatic
      disease. The primary tumor often grows to considerable size before symptoms are
      apparent, which could explain the high rate of metastatic RCC (mRCC). The median
      survival of mRCC after diagnosis is 8 to 12 months and the 5-year survival is
      less than ideal. Traditionally, surgery has been the treatment of choice for
      mRCC. Chemotherapeutic agents tested so far have been disappointing, perhaps
      because of a high expression of the multidrug resistance gene or the high content
      of glutathione in RCC cells. However, the spontaneous regression of mRCC in some
      cases suggests that these tumor cells are responsive to immunologic mechanisms.
      Initial interest has focused on two cytokines, interferon-alpha (IFN-alpha) and
      interleukin-2 (IL-2), with response rates ranging from 15% to 20%. Both IL-2 and
      IFN-alpha are pleiotropic compounds with specific effects on many leukocyte
      subsets, in addition to directly affecting tumor proliferation, angiogenesis, and
      antigen expression. The mechanisms by which these immunoenhancing cytokines exert
      antitumor effects are still unknown. However, many agree that activation of T
      cells and natural killer cells is a pivotal part of the antitumor efficacy. For
      example, some investigators have found that pretreatment levels of natural killer
      cells and T cells predict a response to IL-2 and IFN-alpha in mRCC. Others report
      a relationship between activation of peripheral blood lymphocytes and response to
      cytokine therapy. Expansion of activated T cells in blood during treatment with
      these two cytokines seems to relate to clinical efficacy in patients with RCC.

PMID- 12068390
TI  - Proceedings of the Spring 2001 Current Concepts in Joint Replacement Meeting. Las
      Vegas, Nevada, USA.

PMID- 12068389
TI  - Histamine dihydrochloride and interleukin-2 in the treatment of acute myeloid
      leukemia.
AB  - Despite successful chemotherapeutic remission induction, most patients with acute
      myeloid leukemia still are destined to die from recurrent and refractory disease.
      Strategies to prolong remission and improve survival include high-dose
      chemotherapy, autologous or allogeneic stem cell transplantation, and other
      immunotherapeutic approaches. The focus on interleukin-2 (IL-2) has arisen from
      in vitro demonstration of enhancement of tumor-specific cytotoxic T-lymphocyte
      and natural killer-cell activity after cytokine activation. The local secretion
      of inhibitory substances and oxidative stress by monocyte/macrophage populations
      may inhibit the cytotoxic capacity of these effector cells. Recently, agents
      capable of modulating cytotoxic effector function have been identified, including
      histamine dihydrochloride, which has been shown to act as an inhibitor of
      cellular-mediated free-radical production. In the presence of histamine,
      cytotoxic effector function may be restored. The addition of histamine to IL-2
      based cytokine therapies has resulted in enhanced in vitro cytotoxic T-cell and
      natural killer-cell function and has allowed for the development of lower, and
      thus, less toxic, IL-2 regimens. Preliminary studies of this combination in
      patients with acute myeloid leukemia in remission suggest improved survival with
      tolerable toxicity. The strategy for implementation of IL-2-based immunotherapy
      in patients with acute myeloid leukemia is reviewed.

PMID- 12068391
TI  - Common threads in hip, knee, and shoulder arthroplasty.

PMID- 12068392
TI  - Fixation for the millennium: the hip.
AB  - In primary total hip arthroplasty, the choice for acetabular component fixation
      is relatively simple. For most surgeons now in practice, cementing acetabular
      components is a relatively little practiced skill. That is not to say that good
      results cannot be achieved routinely and that there is anything wrong with this
      approach. Cementless fixation of the acetabulum also is reliable. For revisions,
      cementless fixation has become the standard method for most surgeons. Fixation of
      the femoral component is more controversial. Contemporary cemented stems employ a
      wide variety of design features and surface finishes. Cementless fixation has
      been shown to be effective in many settings. Revision components are largely
      cementless and extensively coated, although there is good evidence that roughened
      surface, tapered components can be effective in the revision setting and that
      stem modularity may allow for greater intraoperative adaptability.

PMID- 12068393
TI  - Fixation of the millennium: the knee.
AB  - Current reports of noncemented fixation for total knee arthroplasty show that
      fixation of the components is durable for 20 years. Noncemented fixation may be
      preferable in patients <60 years old. In revision total knee arthroplasty,
      cemented stems are preferable in patients >70 years old.

PMID- 12068394
TI  - Fixation for the millennium: the shoulder.
AB  - Charles Neer designed his original prosthesis in 1951. It was made of cast cobalt
      chrome alloy and was only press-fit. There was not any significant loosening in
      his original series, but patients complained of easy fatigability. This finding
      was attributed to glenoid issues and a cemented glenoid replacement was
      introduced in 1973. High rates of lucencies were reported and raised issues
      regarding fixation. Cementless glenoid components have been found to have fewer
      lucencies but require metal backing. Higher failure rates have been reported for
      the cementless design versus the cemented glenoids. With humeral fixation,
      symptomatic loosening is not a problem with cement or coated press-fit fixation.
      Long-term outcome studies with cemented and uncemented stems have shown the
      incidence of humeral loosening to be low. Fixation of humeral components should
      be based on bone quality, patient age, prosthetic design, and surgeon preference.

PMID- 12068395
TI  - Management of periprosthetic fractures: the hip.
AB  - Treatment of periprosthetic fractures around a total hip arthroplasty is based on
      fracture timing (intraoperative or postoperative) and fracture location
      (acetabulum or femur). Most intraoperative fractures are treated by ensuring that
      the implant and fracture are stable and employing minor technique modifications
      to ensure that the fracture remains stable postoperatively. Major intraoperative
      fractures require more complex reconstruction. Postoperative fractures associated
      with well-fixed implants typically are treated with open reduction and internal
      fixation. Postoperative fractures associated with loose implants are treated with
      revision and fracture stabilization, usually with specialized revision implants.

PMID- 12068396
TI  - Management of periprosthetic fractures: the shoulder.
AB  - The incidence of periprosthetic fracture during or after shoulder arthroplasty is
      1% to 3% of all shoulder arthroplasties. The frequency with which this injury
      occurs may be increasing, however. Contemporary implants have been designed
      specifically for uncemented use and often have larger proximal bodies. During
      insertion, attempts are made to achieve a tight, line-line fit. Consequently the
      risk for periprosthetic fracture may be higher than estimated.

PMID- 12068397
TI  - Soft tissue balancing: the hip.
AB  - During total hip arthroplasty, femoral offset is restored in only 40% of
      patients. Increased attention to techniques that ensure leg-length and offset
      restoration improve total hip arthroplasty function and minimize the risk of
      complications such as dislocation and limp. Preoperative templating,
      intraoperative leg-length offset measurements, and the availability of high
      offset femoral necks can improve the restoration of offset in 90% of patients.

PMID- 12068398
TI  - Soft tissue balancing: the knee.
AB  - During flexion of the normal knee, the tibia stays within a plane that is aligned
      anterior-to-posterior and passes near the center of the hip, knee, and ankle. To
      align the knee during total knee arthroplasty, the distal femoral cuts are
      aligned in 5 degrees to 7 degrees valgus to the long axis of the femur, and the
      tibial surface is cut perpendicular to the long axis of the tibia. To align the
      knee in the flexed position, the femoral surfaces are resected perpendicular to
      the anteroposterior axis of the femur. After alignment, sizing, and implant
      positioning are done, only tight ligaments are released. This technique generally
      results in a knee that is balanced to varus and valgus stresses in flexion and
      extension, but it often leaves anteroposterior and rotational instability, which
      may require a more highly conforming tibial component or posterior stabilized
      knee.

PMID- 12068399
TI  - Instability after arthroplasty: the shoulder.
AB  - Shoulder instability after total shoulder arthroplasty may be classified as
      posterior, anterior, superior, or inferior. Basic causes include malposition of
      the components, incorrect version of the glenoid or humeral cuts, soft tissue
      contractures or laxity, and cuff deficiency. These may be present as isolated or
      as combined deficiencies. As always, avoidance is best, but instability is the
      commonest complication of shoulder arthroplasty and must be dealt with correctly.
      Recognition of the anatomic cause is crucial. Proper evaluation with radiographs,
      computed tomography, and magnetic resonance imaging is crucial to the treatment
      algorithm. Normally the glenoid is nearly perpendicular to the scapular spine,
      whereas the humeral head is retroverted about 30 degrees with respect to the
      transepicondylar axis. After defining the anatomic problem, proper component
      positioning, elimination of contractures, plication of capsular laxity, and
      establishing cuff integrity ensure the best opportunity for a stable shoulder.

PMID- 12068400
TI  - Shoulder arthroplasty in the face of acute fracture: puzzle pieces.
AB  - Surgical management of acute 4-part humeral fracture-dislocations presents many
      challenges to the orthopaedic surgeon. Intraoperative surgical reconstruction
      requires a detailed understanding of the osseous and the muscular anatomy and
      physiology. The proximal humerus must be reconstructed in a way that establishes
      proper humeral head version and proper myofascial sleeve tension within the
      rotator cuff and deltoid musculature. This article reviews and discusses the
      salient surgical principles and techniques that allow anatomic reconstruction of
      the proximal humerus. Tuberosity placement and fixation techniques are
      emphasized, recognizing that anatomic restoration of the cuff is crucial if the
      patient is to achieve a pain-free and functional limb after joint arthroplasty
      for fracture.

PMID- 12068401
TI  - Staged exchange arthroplasty for shoulder sepsis.
AB  - Eight patients with shoulder sepsis were treated with staged exchange
      arthroplasty using antibiotic-impregnated polymethyl methacrylate spacers shaped
      and fitted to the patient's anatomy after extensive joint debridement.
      Intravenous antibiotic therapy followed for a minimum of 3 months. At the end of
      6 months, the patients were evaluated for any clinical or laboratory signs of
      infection; none were encountered. Exchange prosthetic reconstructions were
      performed using standard implants fixed with antibiotic-impregnated polymethyl
      methacrylate cement. Three patients underwent a revision to total shoulder
      arthroplasty, whereas 5 underwent hemiarthroplasty of the humerus with local
      capsular flap covering of the glenoid. All patients experienced substantial pain
      relief and improvement in function despite limited total overhead motion, showing
      this technique to be a satisfactory salvage procedure for managing sepsis of the
      glenohumeral joint primarily and after total shoulder arthroplasty.

PMID- 12068402
TI  - Case challenges in shoulder surgery: what would you do?
AB  - The management of complex shoulder issues was discussed in an interactive case
      presentation session. Patient scenarios discussed included reoperation of a
      rotator cuff repair with a subscapularis tear; uncemented hemiarthroplasty
      presenting with pain and osteolysis; severe osteoarthritis with all nonoperative
      options exhausted; rheumatoid arthritis with pain and diminished function; and
      significant pain, limited motion, and weakness in an active patient.

PMID- 12068403
TI  - Osteotomy of the knee: is there a seat at the table?
AB  - Osteotomy is an alternative treatment for unicompartmental osteoarthritis of the
      knee. In genu varum, a high valgus closing wedge osteotomy is preferred, with
      overcorrection by 5 degrees. Complications and poor outcomes can be overcome by
      incomplete osteotomy with careful preoperative planning, precise use of cutting
      jigs, compression fixation, and early mobilization and weight bearing. Patella
      baja is related to postoperative immobilization, and unicompartmental
      arthroplasties are more difficult to revise because of bone loss. Supracondylar
      femoral osteotomy is preferred for genu valgum using a lateral opening wedge with
      a toothed plate, allowing easy access to the lateral compartment of the knee.
      Osteotomy, far from being obsolete, has an increasing role in joint resurfacing
      procedures.

PMID- 12068404
TI  - A fresh osteochondral allograft alternative.
AB  - Fresh osteochondral allografts were used for post-traumatic knee defects >3 cm in
      diameter and 1 cm in depth. Harvesting of the grafts was carried out within 24
      hours of the death of the donor, and implantation into the recipient was carried
      out within 72 hours. The grafts were unipolar, fixed by screws, and combined with
      realignment osteotomy if a deformity existed. Meniscal transplantation also was
      performed if indicated. The survivorship of all grafts (plateaus and condyles) at
      7.5 years was 85%. The survivorship of femoral condyle grafts at 10 years was
      85%. Viable hyaline cartilage has been confirmed at 17 years.

PMID- 12068405
TI  - Orthopaedic crossfire--can we justify unicondylar arthroplasty as a temporizing
      procedure? in the affirmative.
AB  - In 1972, unicondylar knee arthroplasty (UKA) was introduced, along with total
      knee arthroplasty (TKA), as an option for managing gonarthrosis. Although the
      early clinical results with the first generation of implants were equivalent to
      those of total knee arthroplasty, little interest in UKA was sustained. If
      unicondylar arthroplasty is to realize a role in the management of degenerative
      arthritis, even as a temporizing procedure, the results must be predictable and
      reproducible. Patient satisfaction must be equivalent to or better than that of
      TKA. Finally, the conversion of UKA to TKA must be uncomplicated, avoiding
      complex reconstructive procedures and the use of revision implants. As documented
      in the literature, UKA achieves these goals. Therefore, we cannot only justify
      UKA as a temporizing procedure, but also as a definitive procedure with long-term
      results that are comparable to TKA for gonarthrosis.

PMID- 12068406
TI  - Orthopaedic crossfire--can we justify unicondylar arthroplasty as a temporizing
      procedure? in opposition.
AB  - The indications for unicompartmental arthroplasty are quite specific. Overall,
      there should be involvement of 1 tibiofemoral compartment, mild malalignment, and
      ligamentous stability. In a review of 250 osteoarthritic knees, these pathologic
      findings were present in 19 patients (8%). Technique, despite improvement in
      instrumentation, still is more demanding than tricompartmental knee arthroplasty,
      and failure to achieve an optimal arthroplasty occurs more frequently. In the
      literature, long-term results with unicompartmental arthroplasty have been
      inferior to tricompartmental arthroplasty. The concept that unicompartmental
      arthroplasty is a temporizing procedure is not a valid one in that the patient
      has to undergo another arthroplasty with all the risks of revision arthroplasty
      surgery. Many of these revision procedures require bone grafting or component
      augmentation. Tibial osteotomy remains the procedure of choice in younger, active
      patients with unicompartmental arthritis (in highly selected patients), and
      tricompartmental arthroplasty is preferred in older, lower demand patients.

PMID- 12068407
TI  - Maximizing flexion after total knee arthroplasty: the need and the pitfalls.
AB  - Currently available knee prostheses can provide 100 degrees to 110 degrees of
      knee flexion, which is usually good enough for most daily activities, such as
      ascending or descending stairs and rising from chairs. Many activities require
      deep knee flexion, however. In Asian countries, deep knee flexion also is needed
      for special cultural activities. Preoperative range of motion, surgical
      technique, prosthesis design, and postoperative rehabilitation are important
      factors that influence postoperative range of motion.

PMID- 12068408
TI  - Knee arthroplasty in post-traumatic arthritis.
AB  - Post-traumatic arthritis of the knee can involve the tibiofemoral joint,
      patellofemoral joint, or both joints. In the tibiofemoral articulation, disabling
      injuries include articular crush, condylar split, shaft involvement, ligamentous
      injuries, or a combination. In the patella, similar injuries include articular
      crush, large or stellate displaced fractures, tendon disruption, or a
      combination. Cementless mobile-bearing knee arthroplasty principles and implants
      can provide satisfactory long-term results in patients with complex post
      traumatic knee arthritis. Primary, resurfacing unicompartmental or total knee
      implants can be used for articular damage, whereas more complex modular or
      constrained implants and osteotomies are needed for angular or combined
      deformities. Bearing exchange revision may be needed for young, active patients
      within 20 years of their initial arthroplasty.

PMID- 12068409
TI  - Total knee arthroplasty in the obese patient: tips and quips.
AB  - As defined by body mass index, 1 of every 3 Americans is overweight. The excuses
      and reasons for this situation are genetic, dietary, cultural, and physiologic.
      Scandinavian literature has shown a higher incidence of gonarthrosis in obese
      patients and some indication of decremental surgical results. Patient selection
      requires identification of the distribution of the obesity and its implications
      for knee surgery. Anesthetic techniques should stress regional approaches,
      oxygenation, and modified postoperative regimens. Surgical incisions should be
      midline, should be longer than normal, and should involve eversion of the patella
      within its fat envelope. Increased tourniquet length and width are mandatory.
      Although wound complications are more common, the overall statistics from total
      knee arthroplasty in obese patients are not discouraging. Greater pressure is
      placed on the surgeon to achieve perfect alignment and balance because the
      patient's weight could unmask the imperfections of the arthroplasty. Only 18% of
      obese people lose weight after joint replacement.

PMID- 12068410
TI  - The stiff total knee arthroplasty: evaluation and management.
AB  - Arthrofibrosis after total knee arthroplasty is a relatively common complication.
      A variety of modalities have been employed to treat this problem, including
      physical therapy, injections, and manipulations. We examined a group of
      consecutive posterior stabilized total knee arthroplasties to determine the
      prevalence of arthrofibrosis, as defined by flexion <90 degrees, and the effect
      of manipulation under anesthesia on outcome. Approximately 11% of the patients
      met the criteria for arthrofibrosis. Manipulation under anesthesia was successful
      in improving flexion from an average of 67 degrees premanipulation to 111 degrees
      postmanipulation. The group that required manipulation did as well statistically
      as the group as a whole, which had a mean flexion of 114 degrees at 1 year.

PMID- 12068412
TI  - Ten steps to an easier revision total knee arthroplasty.
AB  - Revision total knee arthroplasty can be facilitated by proper preoperative
      planning, using an extensile incision, lysing of adhesions on the lateral gutter,
      exposing the medial and lateral aspects of the proximal tibia, and stabilizing
      the patellar tendon. If the patella cannot be everted safely, the surgeon should
      be prepared to do a rectus snip or tibial tubercle osteotomy. The components
      should be extracted axially after separation of the interfaces with a small
      sagittal saw or small osteotomes. The intramedullary canals of the femur and
      tibia should be used as references for the cutting blocks.

PMID- 12068411
TI  - Skin necrosis after total knee arthroplasty.
AB  - Nine patients were treated for skin necrosis after total knee arthroplasty. Eight
      patients had predisposing factors, which may have increased their risk of
      developing wound complications. Seven patients developed necrosis over the
      patellar tendon or tibial tubercle, of whom 6 were treated with muscle flap
      coverage. Two patients developed necrosis over the patella, both of whom were
      treated with local wound care and skin grafting. Successful wound healing and
      salvage of the total knee arthroplasty was achieved in all cases. Treatment of
      necrosis over the patellar tendon or tibial tubercle usually requires muscle flap
      coverage, whereas necrosis over the patella may be treated with local wound care
      and skin grafting.

PMID- 12068413
TI  - Case challenges in knee surgery: what would you do?
AB  - In an interactive case presentation session, the faculty discussed management of
      complex primary and revision knee arthroplasty issues. Principles discussed
      included: preoperative evaluation of the failed knee arthroplasty, intra
      articular versus extra-articular deformity correction, ligamentous balancing,
      managing the unstable total knee arthroplasty, bone deficiency management,
      rotational positioning of prosthetic components, selection of articular
      constraint in the revision knee, and extensor mechanism balancing.

PMID- 12068414
TI  - The structural allograft composite in revision total knee arthroplasty.
AB  - Options in revision total knee arthroplasty with massive bone loss include
      arthrodesis, custom total knee arthroplasty, amputation, and revision with
      structural allograft-prosthesis composites. Advantages of structural allografts
      include their biologic potential, versatility, relative cost-effectiveness, bone
      stock restoration, and potential for ligamentous reattachment. Disadvantages
      include the risk of disease transmission and graft nonunion, malunion, collapse,
      or resorption. Extensive preoperative planning is required to rule out infection
      and to select properly the type and size of allograft and prosthetic implant.
      Implant designs with diaphyseal-engaging stems and increased prosthetic
      constraint often are required. The host site and allograft require meticulous
      preparation to maximize surface contact and mechanical interlock of the allograft
      and host. Allograft fixation must be rigid to allow for incorporation.
      Ligamentous reattachment to the allograft is most successful when done by a bone
      block technique. Common complications include instability and graft collapse.

PMID- 12068415
TI  - The use of impaction grafting in revision total knee arthroplasty.
AB  - Impaction grafting has been used successfully in revision total knee
      arthroplasty. Histology and preliminary clinical results show that this technique
      may be useful in situations in which bone loss is extensive. In contrast to bulk
      allografts, morcellized graft remodels and incorporates with the host. The
      preliminary results and technique are reviewed briefly.

PMID- 12068416
TI  - Managing the infected knee: as good as it gets.
AB  - The clinical presentation is a useful guide for selecting the treatment of an
      infected total knee arthroplasty. Prosthesis retention is indicated in patients
      with infections that occur within 30 days after arthroplasty and in patients with
      well-functioning prostheses who develop an acute late hematogenous infection.
      Debridement attempts should be open and not arthroscopic. When prosthesis removal
      is required, the preferred approach is a delayed reconstructive technique, the 2
      staged reimplantation, rather than a direct-exchange procedure. The use of block
      spacers or mobile articulating devices to deliver high-dose local antibiotics is
      recommended between implant removal and delayed revision surgery. The use of
      antibiotic-loaded acrylic cement for cemented prostheses or antibiotic-soaked
      bone-graft with cementless prostheses is helpful in the overall cure rate of
      infection.

PMID- 12068418
TI  - Press-fit hip arthroplasty: a European alternative.
AB  - The Cement-Less Stem (CLS; Sulzer Medica, Baar, Switzerland) was borne out of the
      proximal fixation and mechanical stability through press-fit and secondary
      osseointegration theories. The biomechanical concept is characterized by the
      three-dimensional wedge-shaped taper, ribs in the proximal region, and the
      undersized tip of the stem. Histologic studies showed that the coarse-grained
      titanium alloy of the CLS provides primary stability. In a series of 300
      consecutive CLS prostheses with a minimum follow-up of 10 years (range, 10-16
      years), femoral survivorship was 95% at 10 years and 90% at 14 years. Stem-bone
      fixation was stable, with bone ongrowth in 97% of patients, stable fibrous
      fixation in 1%, and unstable fibrous fixation in 2%. The CLS grit-blast, press
      fit, collarless, tapered femoral component continues to perform well. Although
      continued surveillance is warranted, the good long-term results justify the
      continued use of the CLS for primary total hip arthroplasty.

PMID- 12068417
TI  - The odyssey of porous-coated fixation.
AB  - Among all primary total hip arthroplasties (THAs) performed at our institution
      between 1977 and 1998, we retrospectively reviewed the outcome of 3,314 THAs
      performed with Anatomic Medullary Locking (AML), Prodigy, and Solution stems (all
      DePuy, Warsaw, IN). These hips included 460 proximally coated stems and 2,854
      extensively coated stems. Survivorship rates for proximally and extensively
      coated stems were >95% at 15 years, using revision for any reason as an endpoint.
      Slight differences in thigh pain, stress shielding, and patient satisfaction were
      not significant. The 2.8% rate of component loosening among proximally coated
      stems was significantly higher than the 1.1% rate observed with extensively
      coated stems. Because of the relatively easy, reproducible surgical technique
      associated with extensively porous-coated stems and the perception of marginally
      better outcome, we prefer to use extensively porous-coated stems for all primary
      THAs.

PMID- 12068419
TI  - Hydroxyapatite: catalyst or conjuror?
AB  - A prospective, randomized, intermediate-term study of 174 patients (199 hips)
      comparing proximally hydroxyapatite (HA)-coated and non-HA-coated surfaces of
      identical stem design is presented. Clinical and radiographic data from 152
      patients (174 hips) confirmed comparable outcomes in both groups according to the
      Hospital for Special Surgery modification of the Postel--d'Aubigne Hip Rating
      System. The non-HA group showed significantly higher (P=.03) activity-related
      thigh pain, however. There were no significant radiographic differences, with all
      stems showing bone ongrowth. The use of HA-coated stems resulted in early
      recovery of function and reduced activity-related trochanteric and thigh pain. A
      possible explanation for the difference is most likely early superior
      osseointegration. HA as a biologic adjuvant should gain widespread acceptance
      because of rapid recovery of function and lesser trochanteric and thigh pain.

PMID- 12068420
TI  - The acetabular component: an elliptical monoblock alternative.
AB  - The major failure mode of cemented or noncemented acetabular fixation is
      osteolysis produced by biologic reaction to polyethylene and metallic debris. A
      monoblock acetabular noncemented component offers advantages in reducing the
      failure mechanism of acetabular cups. First, there is no extra-articular back
      surface polyethylene wear. Second, locking rings that may generate metallic
      debris are eliminated. Third, screw-holes, which decrease the surface area for
      ingrowth, are not needed, and pelvic entrance points for wear debris are
      eliminated. Fourth, an elliptical configuration allows better coaptation of the
      shell to the dome of the acetabulum. I have implanted >2,400 elliptical monoblock
      acetabular cups with a short-term follow-up of 6.5 years, with >4 years of follow
      up in 840 hips. There have been no mechanical failures requiring revision. Four
      patients have been revised for recurrent hip instability, and one has been
      revised for infection. The need to convert to an acetabular component with screw
      fixation because of poor press-fit is <1%.

PMID- 12068421
TI  - Osteonecrosis: avoiding total hip arthroplasty.
AB  - Osteonecrosis of the femoral head afflicts approximately 20,000 new patients per
      year, at an average age of 38. Of the patients seen in our institution, 25% are
      <25 years old. Without treatment, most of these patients can be expected to need
      a total hip arthroplasty. Joint-preserving procedures have a significant failure
      rate, and some have significant morbidity. It is desirable to avoid or delay
      total hip arthroplasty because most patients with osteonecrosis outlive the
      current state-of-the-art prostheses. Four issues need to be weighed to arrive at
      a reasonable algorithm for the preservative treatment of osteonecrosis: i)
      patient risk factors, ii) morbidity of the proposed procedure, iii) size of the
      lesion, and iv) stage of the lesion. All of the issues must be considered to make
      sense out of a complex clinical situation.

PMID- 12068422
TI  - Transfusion options in total joint arthroplasty.
AB  - Concern about the safety of allogeneic blood transfusion, including the risk of
      viral infection and immunosuppression, has led to the development of transfusion
      options in total joint arthroplasty, including intraoperative and postoperative
      blood salvage, autologous donation, hemodilution, and the use of epoetin alfa.
      Intraoperative or postoperative blood salvage has been shown not to be cost
      effective at our institution except in revision hip arthroplasties because not
      enough blood is collected. Autologous donation is not helpful. One third of
      patients undergoing joint arthroplasty have hemoglobin values between 10 and 13
      g/dL preoperatively. The most efficient way to decrease allogeneic risk in these
      patients is epoetin alfa. Epoetin alfa decreases allogeneic risk to 12.9%, which
      is acceptable. Patients with preoperative hemoglobin >14 g/dL undergoing single
      total knee or total hip arthroplasty do not need anything because their
      allogeneic risk is minimal.

PMID- 12068423
TI  - Pain management for joint arthroplasty: preemptive analgesia.
AB  - Scheduled preoperative and postoperative analgesia should be offered in a
      multimodal management model. By a combined drug synergy effect, the central
      nervous system, afferent pathways, and peripheral wound site are modified
      collectively. In an ongoing effort to improve perioperative pain management, we
      retrospectively compared the results of a previously reported pain management
      protocol with 2 more recent groups of patients managed with modified pain
      protocols. In the earlier control protocol, epidural anesthesia was discontinued
      on arrival to the postanesthesia care unit, and regularly scheduled oral opioids
      and intravenous hydromorphone for breakthrough pain were initiated. The first
      more recent group used epidural anesthesia, and the second group used spinal
      anesthesia. Both protocols featured the use of cyclooxygenase-2-inhibiting anti
      inflammatory medication administered for 2 weeks preoperatively and continued for
      10 days postoperatively and patient-controlled analgesia for 24 hours followed by
      scheduled oral opioids.

PMID- 12068424
TI  - Minimal 11-year follow-up of extensively porous-coated stems in femoral revision
      total hip arthroplasty.
AB  - Between 1984 and 1989, 188 consecutive femoral revision surgeries were performed.
      Eighteen patients died or were lost to follow-up, and the remaining 170 patients
      were followed for 11 to 16 years (mean, 14.2 years). Radiographic evidence of a
      bone ingrown stem was present in 82% of the hips, stable fibrous fixation was
      present in 14% of the hips, and 4% of the hips were unstable. Six stems were
      revised to a larger, fully coated cementless implant. Proximal femoral osteolysis
      was seen in 23% of femora but was limited to Gruen zones 1 and 7. No diaphyseal
      osteolysis was seen. The overall mechanical failure rate in this series was 4.1%.
      Failure of fixation correlated highly with extent of bone loss present at the
      time of surgery. On the basis of the radiographic and clinical results at a mean
      follow-up of 14.2 years, we recommend the use of extensively coated femoral stems
      in revision hip arthroplasty.

PMID- 12068425
TI  - The long-term success of modular proximal fixation stems in revision total hip
      arthroplasty.
AB  - A prospective study was carried out on the use of a proximally modular, proximal
      ingrowth noncemented stem in hip revision surgery. There were 109 short stems and
      211 long stems. The mean follow-up was 7 years (range, 2-12 years). No revisions
      were required in the short-stem group for aseptic loosening; 3 (1.4%) revisions
      were required in the long-stem group. Lucency was absent in 91.7% of short-stem
      cases, was low grade in 7.2%, and was high grade in 1.1%. In the long-stem group,
      lucency was absent in 72.9% of cases, was low grade in 24.5%, and was high grade
      in 2.6%. No measurable subsidence occurred in the short-stem group, and 5 mm of
      subsidence occurred early in 2 of the long-stem group. This subsidence stabilized
      subsequently. Osteolysis distal to the sleeve was not observed. A proximal
      ingrowth, proximally modular stem can be used in revision hip surgery.

PMID- 12068426
TI  - Femoral revision: distal fixation with fluted, tapered grit-blasted stems.
AB  - Fluted, tapered grit-blasted titanium stems for revision total hip arthroplasty
      have been used extensively in Europe and have been reported to provide mostly
      favorable results. These stems are tapered to gain axial stability and fluted to
      gain rotational stability in the femoral diaphysis. Grit-blasted titanium
      provides a surface for bone ongrowth. Such implants can solve certain problems
      not addressed easily by other standard revision techniques. The clinical
      durability of modular implants, introduced to make these implants more user
      friendly and more versatile, remains to be proved. These implants require special
      techniques for implantation, particularly when long-stemmed implants are used.

PMID- 12068427
TI  - Impaction grafting: doing it right.
AB  - Impaction grafting has emerged as a useful technique in the armamentarium of the
      revision total hip arthroplasty surgeon. The original technique proposed by Ling
      has been associated with complications, including femoral shaft fractures,
      recurrent dislocations, and uncontrolled component subsidence. Modifications in
      that technique seem to be associated with a reduction in complications. The
      radial impaction grafting technique permits the use of revision femoral
      components with variable stem lengths, neck lengths, and neck offsets. The
      technique seeks to improve the quality of bone impaction and reduce the incidence
      of subsidence. Initial results have been encouraging.

PMID- 12068428
TI  - Management strategies for acetabular defects in revision total hip arthroplasty.
AB  - The management of failed acetabular implants in total hip arthroplasty revision
      surgery requires an algorithm for intraoperative decisions regarding technique
      and implant selection. When > or = 50% of the acetabular host-bone is intact and
      stable, a press-fit ingrowth socket offers a reliable solution. In the presence
      of peripheral, central, or combined defects, a reconstruction ring with compacted
      cancellous allograft is advised.

PMID- 12068429
TI  - Well-fixed acetabular component retention or replacement: the whys and the
      wherefores.
AB  - Occasionally the adult reconstructive surgeon is faced with a well-fixed
      acetabular component that is associated with an arthroplasty problem that
      ordinarily would require removal and replacement of the cup. Removal of a well
      fixed cup is associated with considerable morbidity in bone loss, particularly in
      the medial wall of the acetabulum. In such a situation, retention of the cup with
      exchange only of the polyethylene liner may be possible. As preparation for a
      prospective study, I informally reviewed my experience of cup retention or
      replacement in revision total hip arthroplasty. An algorithm for retaining or
      revising a well-fixed acetabular component is presented here.

PMID- 12068430
TI  - Don't throw away the ring: indications and use.
AB  - Protective rings are a valuable adjunct in revision acetabular surgery. Two types
      of rings are used. The roof ring, which is the smaller of the 2 rings, provides
      support from the ilium to the inferomedial part of the acetabulum. The
      reconstructive ring or cage provides support from the ilium to the ischium. Both
      devices can be used to protect morcellized or structural bone-graft. The roof
      ring can be used with morcellized graft if the ring can make contact with host
      bone at the superior and inferomedial aspect of the acetabulum. If the defect is
      more global but still contained so that the entire acetabulum is filled with
      morcellized bone, the larger reconstructive ring should be used. Small structural
      grafts that support <50% of the cup may be protected by a roof ring. Larger
      structural grafts that support >50% of the cup should be protected by a
      reconstructive ring.

PMID- 12068431
TI  - Polyethylene liner cementation into fixed acetabular shells.
AB  - A patient presenting with a secure cementless acetabular component and with
      femoral head penetration through the polyethylene liner is a common clinical
      problem. Cementing a new liner into the fixed shell is one option. We evaluated
      this option in a clinical series of 17 cases and with a preliminary mechanical
      study. In the 1 clinical failure (5.9%), the failure occurred at the cement-liner
      interface. The most important variable in optimizing the mechanical strength of
      the cemented liner construct was adequate preparation of the cement-liner
      interface. This approach to treating the patient with a fixed cementless shell
      and a worn polyethylene liner can provide a durable construct with minimal
      morbidity.

PMID- 12068432
TI  - [Changes in the concentration of calcium ions and rhythm of protein synthesis in
      the culture of hepatocytes].
AB  - We studied the effects of the chelating agents of extra- and intracellular
      calcium ions, EGTA and BAPTA-AM, and of the inhibitor of Ca2+ release from the
      reticulum, TMB-8, in the kinetics of protein synthesis in hepatocyte cultures. We
      also studied dense cultures capable of self-synchronization of protein synthesis
      oscillations and diluted cultures, in which synchronization is induced by
      phenylephrine or gangliosides (standard preparation of total gangliosides from
      the bovine brain). Preincubation of the diluted or dense cultures in the presence
      of 2 mM EGTA for 1-2 h with subsequent protein assay in a medium with EGTA did
      not affect the kinetics of protein synthesis: no rhythm was found in the diluted
      cultures, while it was preserved in the dense cultures. When the diluted cultures
      preincubated in the presence of EGTA were placed in a medium with EGTA and 2
      microM phenylephrine for 2 min, the rhythm was visualized. The treatment of
      diluted cultures with 100 microM TMB-8 for 5 or 10 min with subsequent washing
      and incubation in a medium with 3 microM gangliosides led to visualization of the
      protein synthesis rhythm, i.e., to the synchronization of oscillations, while no
      rhythm was found in the standard cultures. Preincubation of the diluted cultures
      in a medium with 10, 15, or 20 microM BAPTA-AM did not affect the kinetics of
      protein synthesis. When, after such preincubation, the diluted cultures were
      placed in the medium with gangliosides, the rhythm was visualized. In the dense
      cultures, normally capable of self-synchronization, no rhythm of protein
      synthesis was found after their treatment with 10-20 microM BAPTA-AM for 1 h. The
      transfer of such cultures in the medium with gangliosides led to visualization of
      the rhythm. Thus, calcium affects the kinetics of protein synthesis: after the
      rise of Ca2+ in the cytoplasm was blocked, the rhythm of protein synthesis was
      not visualized due, supposedly, to disturbed mechanisms of medium conditioning.
      However, exogenous gangliosides in the dense or diluted cultures preincubated in
      the presence of BAPTA-AM ore TMB-8 allowed the rhythm visualization, i.e.,
      synchronization may not depend on changes in the intracellular calcium
      concentration.

PMID- 12068433
TI  - [Specific features of nitrogen transformation in the soddy-podzolic soil in the
      areas of habitat of the common vole Microtus arvalis].
AB  - The influence of common vole Microtus arvalis on processes of nitrogen fixation
      and denitrification in the soddy-podsolic soil was studied. In the common vole
      colonies, the level of nitrogen fixation was reliably lower and that of
      denitrification higher, than in the control soil outside these colonies. Nitrogen
      containing excretory products of voles accumulating in the soil are among the
      main factors that determine the activity of these processes.

PMID- 12068434
TI  - [Oribatid mites (Acariformes, Oribatei) as an index of postpyrogenous changes in
      podzol and peat soils of boreal forests].
AB  - Population changes of oribatid mites were studied in a bilberry-moss spruce stand
      and shrub-peat moss pine stand caused by ground fire. The fire resulted in a drop
      of population density and changes in the species composition of mites in both
      forest types. In the case of the spruce stand, the restoration of species
      composition proceeded parallel to the formation of a bilberry-moss cover and
      litter and became distinct four years after the fire. In the case of pine stand,
      the fire enveloped only the peripheral region. After the sphagnum cover burned
      out, the moor dehydration began and the mineralized organogenic substrate
      emerged. Here, the oribatid complex was significantly rearranged and the
      previously dominating moisture-loving species were replaced by the mesophilous
      xerophilous species typical predominantly for mineralized soils. This explains
      why the oribatid species composition in the burned pine stand is more similar to
      that in the control spruce stand than to that in the control pine stand.

PMID- 12068435
TI  - [Cytopathology of plants infected with viruses. Ultrastructure of the leaf cells
      of cereals affected by rhabdoviruses].
AB  - Ultrathin sections of oat, wheat, and ryegrass leaves from healthy plants and
      plants infected with rhabdoviruses by leafhoppers Laodelphax striatellus Fallen
      were studied under the electron microscope. The bacilliform virions often
      surrounded by endoplasmic reticulum (ER) membranes, viroplasm, and tubular
      structures conforming, in diameter and structure, to the rhabdovirion
      nucleocapsid were observed in the cytoplasm of leaf cells of the diseased plants.
      The cereal pseudorosette virus [(165-200) x (63-70) nm, CPV] is the causative
      agent of the disease of cereals in Siberia. The mycoplasma-like organisms were
      found in the phloem cells of plants infected with CPV. The cereal mosaic virus
      [(360-420) x (56-64) nm, CMV] is the causative agent of the disease of cereals in
      the Russian Far East. CMV appears to be a strain of the northern cereal mosaic
      virus occurring in Japan and China.

PMID- 12068436
TI  - [Simulation of the migration process of human epidermal keratinocytes over three
      dimensional collagen gel].
AB  - We developed a novel model for studying migration of keratinocyte colonies over
      3D collagen gel. It was shown that keratinocytes previously cultured on plastic
      and then seeded on the surface of collagen gel proliferate more actively than the
      primary cells. The gel density could significantly affect the morphology and
      migration of keratinocyte colonies. Modification of collagen gel by fibronectin
      like protein or poly-L-lysine altered the morphometric parameters of colonies
      without significant changes in the velocity of migration.

PMID- 12068438
TI  - [On the principle of substance stability and thermodynamic feedback in hierarchic
      systems of the bio-world].
AB  - The creation of structural hierarchies in open natural biosystems within the
      framework of quasi-closed systems is investigated by the methods of hierarchic
      thermodynamics (thermostatics). During the evolution of natural open systems,
      every higher hierarchic level j appears as a consequence of thermodynamic self
      organization (self-assembly) of the structures of the lower (j-1)-th level. Such
      a self-assembly proceeds as a result of stabilization of the j-th level. This is
      related to the Gibbs' (Helmholtz') specific function of formation of the
      structure of the j-th level tending to a minimum. As a result of action of the
      principle of substance (matter) stability, the structures of the j-th level are
      enriched with less stable structures of the (j-1)-th level in the course of
      evolution. This provides a thermodynamic feedback between the structures of the
      higher j-th level and lower (j-1)-th level, thus preventing full structural
      stabilization of the j-th level and causing "thermodynamic rejuvenation" of
      biosystems. The latter enhances "thermodynamic" deceleration of evolution and
      practically unlimited maintenance of life. Examples of quantitative correlations
      are provided that call for further application of the substance stability
      principle to living and nonliving hierarchic structures.

PMID- 12068437
TI  - [Regeneration of gastrocnemius muscle and state of immune system in radiated rats
      under the influence of He-Ne laser].
AB  - We studied the influence of a low-energy He-Ne laser on the regeneration of the
      transected gastrocnemius muscle and state of the thymus and bone marrow in adult
      mongrel rats irradiated at 6 Gy using the histological, morphometric, and
      cytogenetic methods. The laser influence on both rat hind limbs (at total doses
      of 9.0-10.8 J/cm2) during the first 14 days after transection enhanced the
      regenerative capacity of the skeletal muscle traumatized as a result of
      irradiation, and reduced cytogenetic damage in the bone marrow and thymus cells.
      The changes in the thymus mass and histology suggest that the functional load on
      the thymus increased under the experimental conditions.

PMID- 12068439
TI  - [Biochemical (enzymatic) indication and testing of the ecological state of the
      hydrosphere].
AB  - The river and lake water of Transuralia (Ob, Yenisei, and Tom rivers) and the
      Altai District (Katun River, Teletskoe Lake, and Korbu Waterfall) were studied
      for the first time using modern enzymatic methods. The self-purifying capacity of
      water and their quality were assessed according to the enzymatic test-systems.

PMID- 12068440
TI  - [Influence of phytohormones on development of conidial inoculum of causative
      agents of the phlox and barley powdery mildew].
AB  - We studied the role of phytohormones: zeatin, kinetin, and abscisic acid, in the
      regulation of development of the conidial inoculum of Erysiphe cichoracearum DC.
      f. phlogis Jacz. and E. graminis DC. f. hordei Marchal. When the pathogen conidia
      were in direct contact with phytohormones, the intensity of their germination
      significantly increased. In the presence of cytokinins, the amount of normal
      appressoria decreased and that of abnormal growth tubes increased. On the phlox
      leaves treated with cytokinins, the intensity of germination of the conidia
      increased, as compared to the control, while abscisic acid exerted the opposite
      effect. The treatment of barley leaves with cytokinins did not affect markedly
      the development of conidial inoculum, as compared to the control, while abscisic
      acid significantly decreased the intensity of germination of the conidia. On the
      leaves of different Phlox species, the degree of germination of the conidial
      negative correlated with their resistance against the powdery mildew. The role of
      cytokinins in pathogenesis of biotrophic fungi is discussed.

PMID- 12068441
TI  - [Specific features of the photosynthetic system in the kidney bean (Phaseolus
      vulgaris L.) in the southern Moscow region].
AB  - The main patterns of the functioning of the photosynthetic system of the French
      bean were established on the basis of comparative tests of eight cultivars and
      varieties. Some agrotechnical methods were developed which enhance the highest
      efficiency of the plant's photosynthetic activity. The data obtained are
      essential for the introduction of promising varieties of the bean cultures in the
      nonchernozem zone of Russia.

PMID- 12068442
TI  - [Comparison of species-specific bird sound signals and human speech sounds].
AB  - We carried out a comparative study of spectral-prosodic characteristics of bird
      vocalization and human speech. Comparison was made between the relative
      characteristics of the fundamental frequency and spectral maxima. Criteria were
      formulated for the comparison of bird's signals and human speech. A certain
      correspondence was found between the vocal structures of birds and humans. It was
      proposed that in the course of evolution, man adopted the main structural
      principles of his acoustic signalling from birds.

PMID- 12068443
TI  - [The role of endogenous peptides in the development of long-term posttetanic
      potentiation].
AB  - Using the model of long-term posttetanic potentiation (LTP) in slices of the
      olfactory cortex of rat brain, we have tested a hypothesis according to which
      activation of nerve cells results in a release of neuromodulatory factors into
      extracellular space; these factors, diffusing over significant distances, are
      capable of synchronously modifying the initial reactivity of neuronal
      populations. Using the technique of bioassay, i.e., transfer of perfusate from
      the tetanized donor slice to the recipient slice, in combination with
      pharmacological and neurochemical techniques, we found that in response to
      excitation, the cells of olfactory cortex slices secrete peptides. This
      observation confirms the above hypothesis. The spectrum of released peptides
      changes depending on the degree of cell excitation and, in addition, is frequency
      dependent. It has been demonstrated that the key target of these peptides are N
      methyl-D-aspartate and glutamate receptors. We propose that two peptide pools are
      involved in the initial and late phases of LTP. The possible significance of
      peptide cell regulation in mechanisms of neuronal plasticity is discussed.

PMID- 12068444
TI  - [The effect of antifreeze glycoproteins on survival and quality of fish
      spermatozoa under the conditions of long-term storage at +4 degree C].
AB  - It was already shown that antifreeze glycoproteins isolated from the blood of
      fish occurring in circumpolar regions inhibited the growth of ice crystals both
      in vitro and in vivo. When the spermatozoa were frozen to liquid nitrogen
      temperature, addition of antifreeze glycoproteins to cryoconserving media made it
      possible to decrease twofold the concentration of the synthetic cryoprotector
      dimethylsulfoxide without the loss and even with a certain increase in the number
      of viable spermatozoa. This effect was observed in the case of combined, rather
      than separate, addition of the fraction of weakly active (low molecular weight)
      and active (high molecular weight) antifreeze glycoproteins. Here, we studied the
      effect of antifreeze glycoproteins on the survival of carp spermatozoa under
      storage at +4 degrees C for varying periods of time. In the presence of total
      fraction of low and high molecular weight antifreeze glycoproteins (2 and 10
      mg/ml) added in a physiological proportion (3:1), the survival of spermatozoa
      increase but this increase did not depend linearly on the medium concentration of
      protein. Low and high molecular weight antifreeze glycoproteins added separately
      (10 mg/ml) either did not affect or slightly affected the preservation of cells.
      The hypothermic effect of antifreeze glycoproteins in water was significantly
      higher than in a medium with salt activator.

PMID- 12068446
TI  - Neuroradiographic imaging: techniques and safety considerations.

PMID- 12068445
TI  - [Specific interaction between esterases and 2-butylthio-2-thio-1,3,2
      oxazaphosphorynane and its cyclic and acyclic analogs].
AB  - We studied the anticholinesterase and anticarboxylesterase effects of 1,3,2
      oxazaphosphorynane derivatives and certain cyclic and acyclic analogs on the two
      enzymes of homoiotherms (ACE from human erythrocytes and BuCE from horse serum)
      as well as the enzymes from insect tissues (the nerve cord of the American cock
      roach and the cephalic region of the domestic fly). The differences in in vitro
      antiesterase activity of cyclic thionic and the corresponding oxo derivatives of
      phosphorinane were revealed. The mechanism of the esterase active center
      phosphorylation not only splitting off the outgoing group (in vivo) but also
      opening the cycle by P-O bond (in vitro and possibly in vivo) is usually proposed
      to explain the higher inhibiting activity of the thionic compounds compared to
      the oxonic ones. The possible involvement of this phosphorylation mechanism in
      the synergistic activity of the studied compounds is discussed.

PMID- 12068447
TI  - Neurologic aspects of rheumatologic disorders.

PMID- 12068448
TI  - Multiple sclerosis.

PMID- 12068449
TI  - Infections.

PMID- 12068450
TI  - Nervous system neoplasms.

PMID- 12068451
TI  - Endocrine aspects of epilepsy.

PMID- 12068452
TI  - Epilepsy.

PMID- 12068453
TI  - Movement disorders.

PMID- 12068454
TI  - Peripheral nerve disorders.

PMID- 12068455
TI  - Muscle disease.

PMID- 12068456
TI  - Migraine and other headache conditions.
AB  - Migraine and other headache conditions are relatively common during pregnancy.
      Physicians and other primary health care providers should not assume that because
      a patient presents with headache alone, such symptoms can be taken lightly. Most
      patients do not develop new-onset headache during pregnancy, and all patients who
      do develop such a condition must be evaluated thoroughly. Similarly, patients who
      develop any change in their headache condition must undergo a careful evaluation.
      Fig. 3.1 is an algorithm to aid in evaluating pregnant patients with headache.
      Postpartum headaches also must be evaluated and treated appropriately. In most
      cases of headache during pregnancy and postpartum, the patient is suffering with
      a benign medical condition. Even so, quality of life is an important
      consideration in preserving the patient's physical and emotional well-being (102,
      103). A stepwise approach to symptomatic treatment should be provided for all
      patients. A high index of suspicion for nonbenign causes of headache will assist
      in decreasing morbidity and mortality to the mother and fetus.

PMID- 12068457
TI  - Developmental disabilities.

PMID- 12068458
TI  - Paraplegia.

PMID- 12068459
TI  - Psychiatric disorders.

PMID- 12068460
TI  - Cocaine and alcohol use.

PMID- 12068461
TI  - Complementary and alternative medicine.

PMID- 12068462
TI  - Legal issues: roles of physicians in preventing fetal harm.

PMID- 12068463
TI  - Neurologic aspects of eclampsia.

PMID- 12068464
TI  - Cerebral ischemia in pregnancy.

PMID- 12068465
TI  - Intracranial hemorrhage.

PMID- 12068466
TI  - Maternal head trauma.

PMID- 12068467
TI  - Critical care management of neurologic catastrophes.

PMID- 12068468
TI  - Low back pain.

PMID- 12068469
TI  - Private concordat. Flexible friends.
AB  - A survey of acute trusts and health authorities suggests that expenditure in the
      private sector has more than doubled since the signing of the concordat in
      October 2000. But it still represents less than 1 per cent of total acute
      spending. Most of the spending was for orthopaedic surgery, made under short
      term, cost-per-case deals. The need for increased capacity was the main motive
      for using the independent sector. More than three-quarters of respondents cited
      prices in the independent sector as a barrier to greater collaboration. There is
      little evidence of NHS organisations and those in the independent sector forming
      partnerships for long-term service planning.

PMID- 12068470
TI  - Patient involvement. It's good to talk.
AB  - Feedback from patients in an acute trust found concerns centred on a lack of
      information, staff attitudes, cleanliness and lack of privacy. Improvements
      introduced include calmer mealtimes, more ward cleaning, a new style of hospital
      nightgown, and offering a free toiletries bag for emergency admissions. Including
      patients and carers at ward sisters' development days is a powerful tool in
      influencing staff attitudes.

PMID- 12068471
TI  - Telephone assessment. Lines of inquiry.

PMID- 12068472
TI  - Open space. Contract killer?

PMID- 12068474
TI  - [Therapeutic maneuvers in the treatment of paroxysmal positional vertigo: can
      they indicate a central genesis?].
AB  - Typical Paroxysmal Positional Nystagmus (PPNy) is a highly specific clinical
      finding that indicates the existence of a specific peripheral lesion: Paroxysmal
      Positional Vertigo (PPV). However, besides this typical nystagmus of high
      topodiagnostic significance, atypical PPNy's are also frequently found. Such
      atypical findings can lead one to suspect a central vestibular system pathology
      and often require additional diagnostic testing. Of 1805 patients with complaints
      of vertigo, 305 proved affected by PPV. The present study evaluated how patients
      affected by the posterior semicircular canal PPV (278/305, 91.2%) responded to
      canalith repositioning maneuvers. In 246 patients (88.5%) the Semont maneuver was
      performed as simplified by Toupet, while the remaining 32 subjects (11.5%) were
      treated with the Epley maneuver as modified by Herdman. The Semont maneuver
      provides the relief of symptoms in 96% of patients while the Epley maneuver
      resolved 78% of cases. The patients that did not respond to the maneuvers, even
      after several attempts, were subsequently treated using "habituation"-based
      rehabilitation techniques (the Brandt-Daroff technique and Vestibular Habituation
      Training). The presence of atypical PPNy was found in 57 subjects. Of these, the
      liberatory maneuver always resolved the PPV. In the present study, the choice to
      perform a neuroradiological study was based on the lack of response to physical
      therapy, whether performed with liberatory maneuvers or with habituation
      techniques. In 2 of the 3 cases of PPV which remained unchanged despite
      treatment, imaging revealed a severe expansive CNS pathology. In these patients
      the dizziness complaints disappeared after neurosurgery: this fact appears to
      confirm the central origin of these PPNy cases. These data clearly indicate that
      the results of PPV treatment must be carefully evaluated. In cases of PPV of the
      PSC, when either typical or atypical PPNy persists one month after diagnosis,
      with no appreciable period of remission, neuroradiological tests should be
      performed in order to rule out any CNS pathology.

PMID- 12068473
TI  - [Balance disorders: a proposal of a new diagnostic methodology from the medico
      legal standpoint].
AB  - Balance impairment is the object of requests for remuneration in 20-50% of the
      cases of cranial trauma. Most patients present slight disequilibrium following
      cranial traumas not involving concussion or cervical distraction. The various
      methods used in Italy to evaluate the biological damage score balance annoyances
      on a percentage basis ranging from 1% to 25% and base evaluation on vestibular
      testing results. The Authors feel that such evaluation approaches are limited.
      Indeed, since compensation mechanisms come into play, vestibular lesions are not
      always symptomatic. This means that the lesions detected solely through
      vestibular testing are not necessarily indicative of the extent to which the
      subject is affected. Furthermore, some extravestibular lesions can give rise to
      balance impairments which will go undetected by vestibular examination. Finally,
      an universally accepted diagnostic protocol still doesn't exist. In this work the
      Authors present a new method for balance impairments evaluation. While this
      technique still involves the normal evaluation range for vestibular damage (1
      25%), it is based on the disturbance indicated by the patient rather than on the
      instrumentally detected damage. To objectively determine the real existence of
      the symptom, the Authors also propose a specific diagnostic strategy for each
      symptom, thus overcoming the problem of a diagnostic standard. The initial
      results, obtained on 56 subjects evaluated for post-traumatic balance impairment,
      show substantial agreement with previous methods. Our method allows to better
      recognize modest damage--for the most part extravestibular which go unrecognized
      with the conventional methods--and significantly modify the amount of more
      extensive damage, expression of vestibular damage which does not correspond to
      equally significant symptoms.

PMID- 12068475
TI  - Combination of surgery and gamma knife radiosurgery--a therapeutic option for
      patients with tumors of nasal cavity or paranasal sinuses infiltrating the skull
      base.
AB  - The purpose of this study was to investigate whether patients operated for skull
      base-infiltrating malignant tumors of the nasal cavity and/or the paranasal
      sinuses benefit from an additional Gamma knife radiosurgery. CASE SERIES: eight
      consecutive patients, (male: female ratio = 1:1, mean age = 52 years, range 34 to
      79 years) presented with 2 cyclindric cell carcinomas, 2 adenocarcinomas, 2
      malignant neuroblastomas, 1 squamous cell carcinoma, 1 amelanotic melanoma. Tumor
      stages (UICC) were: 1 T1, 3 T2, 3 T3, 1 T4, all N0, all M0. All patients were
      primarily treated surgically and 4 weeks later received additional stereotactic
      radiosurgery. Follow-up was based on computerized tomography (CT), magnetic
      resonance imaging (MRI), endoscopy, and biopsy. The course of disease was
      compared to tumor courses with surgery but without radiosurgery reported in
      literature. Four times endoscopic endonasal surgery (EES), once EES in
      combination with fluorescein technique, once EES plus external approach of
      frontal sinus, once lateral rhinotomy was performed. All 8 cases underwent
      radiosurgery (Leksell gamma knife) 4 weeks after surgery. Thirty six months after
      radiosurgery 6 patients were alive (4 patients without evidence of disease, 1
      patient with pulmonary metastasis but without local recurrence, 1 patient with
      regional metastasis but no local recurrence), 1 patient died 11 months after
      treatment due to disease, 1 patient died due to a second malignancy. No negative
      or adverse effects due to radiosurgery were observed. The combination of
      microsurgery with Leksell Gamma knife radiosurgery appears to be an encouraging
      therapeutic option. To date no adverse effects have been observed in the
      presented cases.

PMID- 12068476
TI  - [Recurrent benign tumors of parotid gland: the role of the surgery].
AB  - Parotid gland tumor recurrences can prove problematic both in terms of facial
      nerve trauma during surgery and for the possible transformation into malignancy.
      Between 1981 and 2001 a total of 40 patients (23 women, 17 men; average age 48;
      age range 20-79 years) underwent surgery for recurrent parotid gland tumors. The
      average time between the first and the second surgical procedures was
      approximately 10 years. Five subjects underwent surgery several times for the
      same pathology. The Authors feel that MRI imaging is an essential tool for the
      evaluation of infiltrations into the soft tissues. The following surgical
      procedures were performed: enucleation in 2 cases; exofacial partial
      parotidectomy (PP) in 1; lower polar PP with functional neck dissection in 1;
      total parotidectomy (TP) with preservation of the facial nerve in 31 cases; TP
      with functional neck dissection in 2; TP with sectioning of the facial nerve in 2
      and TP with transmandibular buccopharyngectomy and myocutaneous gran dorsal
      muscle flap in 1 case. Histology proved positive for the following: pleomorphous
      adenoma in 21 cases, adenocarcinoma in 11, aggressive fibromatosis in 2,
      cystadenolymphoma in 1, parotiditis in 1, lipoma in 1, cystic lymphoid
      hyperplasia in 1, histiofibrosarcoma in 1 and neurofibrosarcoma in 1. The
      surgical technique used was retrograde dissection of the facial nerve starting
      from one of the peripheral branches. Post-operatively, whenever a facial
      paralysis was encountered it proved difficult to recover. Paralysis of the nerve
      was permanent only in the 2 subjects where sectioning proved necessary because of
      infiltration by carcinoma. In 6 subjects recovery of the paralysis took one year,
      in 4 it took 6 months and in 2 other cases 3 months. In 22 cases there was only a
      slight paralysis of some branches which recovered during the post-operative
      period. We do not have definitive data on 4 subjects either because the period of
      time since surgery is still too short or because they did not come in for
      subsequent check-ups. The results of our study show that total parotidectomy
      should be the treatment of choice in case of benign parotid gland tumors and in
      particular for pleomorphic adenoma.

PMID- 12068477
TI  - [Highly malignant papillary cystadenocarcinoma of the tongue: a case report].
AB  - Papillary cystadenocarcinoma (PC) of the tongue is an extremely rare malignant
      neoplasm arising from the minor salivary glands. Its anatomopathological features
      are sufficiently characterized although clinical manifestation and biological
      behavior are not yet well defined. The Authors describe a highly malignant case
      of PC of the tongue in a 71-year-old man treated with surgery, followed by
      radiotherapy. Clinical and anatomopathological characteristics of this rare
      neoplasm are described. A review of the international literature confirms how
      unusual this disorder is and explains the poor tumor histotype characterization.
      Finally the Authors assert that this is the first case of highly malignant PC
      with localization limited to the tongue reported in literature. The Authors
      conclude suggesting a clinical-therapeutic procedure to deal with this rare
      pathology.

PMID- 12068478
TI  - [Epithelial leiomyosarcoma of gingiva: a case report and review of literature].
AB  - Epithelioid leiomyosarcoma (EL) is a rare malignant tumor of mesenchymal origin.
      The Authors review the literature and report a case of gingival epithelioid
      leiomyosarcoma in a 40-year-old patient. In this case the leiomyosarcoma was
      located in the lower front dental group and invaded the symphysis menti. A
      segmentary mandibolectomy was performed with reconstruction using a non
      revascularized autologous iliac bone graft. The differential diagnosis of primary
      EL is quite complex and it is grouped with other sarcomas, sarcomatoid carcinoma,
      myoepithelioma, amelanotic melanoma and metastases from gastrointestinal EL.
      Anatomopathological examination and immunohistochemical study enabled a
      definitive diagnosis of primary EL of gingiva. The follow-up calls for clinical
      radiological check-ups every three months for the first year and every six months
      thereafter. One year after surgery there were no signs of recurrence.

PMID- 12068479
TI  - [Ulcero-necrotic and lymphoproliferative naso-paranasal lesions in cocaine
      abuse].
AB  - In this work are reported two clinical cases of cocaine abusers with destructive
      lesions of nasal-paranasal cavities. The clinical presentation and the absence of
      a positive history of drug addiction led to a differential diagnosis between
      lymphoma, idiopathic median line granuloma and Wegener granulomatosis.
      Biochemical and serological examinations did not prove conclusive. The diagnosis
      was finally formulated on the basis of the documented presence of cocaine in the
      biological fluids. Emphasis is placed in the difficulty of obtaining a reliable
      case history in this type of patients. Moreover, the Authors point out that it is
      advisable to test for drugs in the biological fluids prior to undertaking time
      consuming diagnostic procedures for pathologies which are extremely rare in the
      West countries.

PMID- 12068480
TI  - Effects of rumen fluid collection site on microbial population structure during
      in vitro fermentation of the different substrates quantified by 16S rRNA
      hybridisation.
AB  - Rumen fluid samples from a cow were withdrawn manually from the feed mat (solid
      phase) or the liquid phase below this mat and incubated in vitro with wheat
      straw, sorghum hay and a concentrate mixture. From the inoculum and several
      samples collected during in vitro incubation RNA was extracted to assess
      microbial population size and structure. RNA content recovered from the solid
      phase rumen fluid was significantly higher than from the liquid phase. The
      composition of the microbial population in the solid phase material was
      characterised by a high proportion of Ruminococci. Neither the proportion of
      other cell wall degrading organisms (Fibrobacter and Chytridiomycetes) nor the
      Eukarya and Archaea populations differed between the two sampling sites. Gas
      production was higher when substrates were incubated with solid phase than with
      liquid phase rumen fluid regardless of sampling time. However, the higher level
      of gas production was not accompanied by a corresponding increase in true
      digestibility. The RNA probes showed that during in vitro incubation with liquid
      phase rumen fluid, the eukaryotic population was inactive no matter which
      substrate was used and the activity of methanogens (Archaea) was lower than with
      solid phase rumen fluid. The population pattern of the cell wall degrading
      organisms was influenced mainly by the substrate fermented, and to a smaller
      extent by the inoculum used for in vitro fermentation.

PMID- 12068481
TI  - Impact of diets varying in dietary fibre characteristics on gastric emptying in
      pregnant sows.
AB  - The effects of feeding two fibre-rich diets with contrasting solubility and a
      concentrated low dietary fibre on the rate of gastric emptying were examined in
      six gastric cannulated pregnant sows. Additionally, it was examined whether any
      effect could be related to the physico-chemical properties of digesta, i.e.
      viscosity and/or water binding capacity. The sows were fed each diet for one week
      in a 3 x 3 Latin Square design and the samples were taken in a randomised order
      0.5, 1, 2, 3, 5 and 15.5 h after the morning meal. The stomach contents were
      evacuated through the gastric cannula once daily. The evacuated gastric digesta
      was quantified and a representative sample was taken to determine its viscosity,
      water binding capacity and its content of dry matter, dietary components and
      solid (Cr2O3) and liquid (polyethylene glycol) phase markers. The flow of liquid
      digesta was calculated as the difference between digesta and dry matter.
      Increasing the content of dietary fibre in the diet led to higher recovery of
      liquid digesta but did not have any significant effect on the gastric emptying of
      dry matter and dietary components. The effect of dietary fibre could not be
      attributed to the viscosity of the liquid phase of digesta but might be related
      to the ability of the increased gastric dietary fibre content to hold water. The
      stomach selectively retained the insoluble dietary fibre components most
      noticeably seen with the bran-supplemented diet where the concentration of
      insoluble NSP in digesta increased significantly from 2 hours and onward.

PMID- 12068482
TI  - The concentration of plasma triacylglycerols in horses fed diets containing
      either medium chain triacylglycerols or an isoenergetic amount of starch or
      cellulose.
AB  - In a Latin square design, six horses were fed hay and concentrates with
      isoenergetic amounts of either starch, cellulose or medium chain triacylglycerols
      (MCT). The dietary variables provided on average 22% of total dietary net energy.
      Plasma triacylglycerols and other variables of lipid metabolism were determined.
      The experimental periods lasted 21 days. Blood samples were taken just before the
      morning meal and three and six hours later. The diet rich in MCT significantly
      raised the plasma level of triacylglycerols when compared to either the starch-
      or cellulose-rich diet. The plasma concentrations of 3-hydroxybutyrate, total
      cholesterol and phospholipids were significantly higher when the horses were fed
      the ration with MCT instead of either cellulose or starch. Postprandial insulin
      concentrations were lowest for the MCT diet, and concentrations of free fatty
      acids were highest. Lipoprotein lipase activity was not significantly different
      for the three diets. Our study does not support the idea that cellulose feeding
      generates sufficient acetic acid in the caecum and colon, so that it would
      enhance the provision of cytosolic acetyl-CoA which in turn would stimulate
      hepatic fatty acid synthesis and then raise plasma triacylglycerols.

PMID- 12068483
TI  - Research note: effect of Bacillus cereus on performances of growing bulls.
AB  - The effect of including Bacillus cereus (BC) in a diet of growing bulls was
      examined. 64 German Holstein bulls (initial body weight: 187 kg) were allotted to
      one of two treatments (control and BC). The bulls were fed corn silage ad libitum
      and a restricted amount of concentrate (without BC or with 100 mg BC/kg). They
      were slaughtered with a final body weight averaging 555 kg. No significant
      treatment differences were detected for any feedlot performance or carcass
      characteristics measured. Bulls fed BC had a daily weight gain of 1472 g, control
      animals of 1425 g. Based on these findings, it may be concluded that under these
      conditions the inclusion of BC will not significantly improve performance of
      growing bulls.

PMID- 12068484
TI  - Butyric acid stimulates rumen mucosa development in the calf mainly by a
      reduction of apoptosis.
AB  - In ruminants the stimulation of papillar growth by butyric acid is well described
      but effects on mitosis and apoptosis are not known. To clarify the effect of
      short chain fatty acids three groups of three calves received a basic ration of
      100 g hay per day for 6 weeks and additionally milk replacer. From these, two
      groups were fed with increasing amounts of the salts of either propionic acid (53
      to 390 g) or butyric acid up to (54 to 326 g). The control group instead received
      an additional isocaloric amount of milk replacer. Mitosis was characterized by
      Ki67 immunoreactivity, apoptosis by a modified TUNEL assay and by electron
      microscopy. The feeding regimes led to significant differences of papillar
      length, increasing from 1.0 mm (controls) to 2.2 mm (propionic acid) and 4 mm
      (butyric acid). This enlargement was partly explained by an increased mitotic
      rate for the two fatty acid groups. The difference between the fatty acid groups
      was mainly explained by different apoptotic rates which were only one third for
      butyric acid compared to propionic acid (P < 0.001). In conclusion, butyric acid
      is a specific inhibitor of ruminal apoptosis in vivo.

PMID- 12068485
TI  - Long-term care wrestles with 'granny cams'.

PMID- 12068486
TI  - Union organizers look at nursing facilities.

PMID- 12068487
TI  - HHS proposes HIPAA privacy rule changes.

PMID- 12068488
TI  - Bioterrorism: better safe than sorry.

PMID- 12068489
TI  - Staffing strategy is win-win for providers.

PMID- 12068490
TI  - Patients respond to aquariums.

PMID- 12068491
TI  - IT strategies: a wide range of choices.

PMID- 12068492
TI  - [The prolonged action of an insulin peptidomimetic by the substitution of L-amino
      acid for its D-isomer].
AB  - The synthesized decapeptide represents functionally important site for binding to
      the insulin receptor. Amino acid residues at position, 1-8 correlate with B-chain
      of insulin at position B19-B26, and the residues at position 9-10 correlate with
      A-chain at position A20-A21. The new peptide was obtained by substitution of two
      aromatic L-amino acid residues (B24 and B26) for their D-optical isomers. These
      peptides were tested with cell cultures L929 and PC12 (glucose uptake). Increased
      concentration of peptides correlated with stimulation of glucose uptake by cells.
      Studies carried out on animals with streptosotocine-caused diabetes showed that,
      synthesized peptides were able to decrease glucose level in blood, but
      decapeptide with D amino acid showed a more pronounced effect compared to the
      decapeptide with L amino acid.

PMID- 12068493
TI  - [The role of alphavbeta3 integrin in changes of the invasive phenotype in CP
      transformed fibroblasts with multiple drug resistance].
AB  - A line of Syrian hamster RSV-ransformed fibroblasts having resistance to a number
      of cytostatics was shown to differ from the parental drug-sensitive line by an
      extremaly low expression of the integrin alpha v beta 3. In vitro invasive
      activity of the drug-resistrant cells appeared to be lower than that of their
      drug-sensitive counterparts. The role of integrin alpha v beta 3 in malignant
      phenotype and multiple drug resistance of tumor cells is discussed.

PMID- 12068494
TI  - [Screening of mutations in genes of pro-opiomelanocortin in patients with
      constitutional exogenous obesity].
AB  - Proopiomelanocortin (POMC) is a precursor of ACTH, beta- and gamma-liportopins,
      alpha-, beta- and gamma-MSH, beta-endorphin. alpha-, beta- and gamma-MSH are
      synthesized by hypothalamus neurons, and leptin stimulates their synthesis. These
      hormones regulate food consumption and energy metabolism by via melanocortin
      receptors (MC3-R and MC4-R) in hypothalamus. Screening mutations in the coding
      region of human POMC has been carried out with PCR, SSCP and DNA sequencing and
      the association study of these mutations and human obesity has been performed.
      Group of patients with the exogenous obesity (BMI 37.8 +/- 6.8 kg/m2) consisted
      of 228 persons (173 women and 55 men). 145 blood donors (67 women and 78 men)
      without obesity (BMI J25 kg/m2, 23.1 +/- 2.2 kg/m2) and 170 women without
      apparent obesity at the beginning of the study were included in the control
      group. 8 polymorph sites: insertions; missense and silent mutations have been
      identified in the coding region of POMC. Among them 1) two heterozygous
      mutations: the insertion of 6 b.p. (GGGCCC) in codon 176 inducing the insertion
      of two amino acid residues (Arg-Ala) in POMC and nonsense mutation (G-7316-T) in
      codon 180 of gamma-LTH coding region of the same DNA chain were identified in 4
      women (5.8%) out of 69 patients with morbid obesity (BMI 40-53 kg/m2). These
      mutations were not found in control (n = 315). 2) The new heterozygous mutation T
      7130-C (Phe118Leu) in active site of alpha-MSH has been identified in POMC gene
      of a woman suffering with obesity since the early childhood. 3) Mutation A-7341-G
      (Glu188Gly) seemed to have a protective effect because it was revealed more
      frequently in control (3.9%) than in obese patients (0.66%). The results of
      genetic study of two pedigrees suggested the dominant influence of the first two
      mutations (1 and 2) on woman obesity.

PMID- 12068496
TI  - [Prostate-specific membrane antigen and its role in diagnosis of prostate
      cancer].
AB  - This paper reviews recent achievements of the employment of prostate specific
      membrane antigen in the diagnostics of prostate cancer.

PMID- 12068497
TI  - [Nitric oxide. The role of guanylate cyclase in its physiological effects].
AB  - In this review the molecular mechanism underlying the antihypertensive and anti
      aggregatory actions of nitric oxide (NO) are discussed. It has been shown that
      these effects are directly connected with the activation of soluble guanylate
      cyclase and the accumulation of cyclic 3',5'-guanosine monophosphate (cGMP). The
      data concerning the basic chemical characteristics of guanylate cyclase, such as
      the subunits structure, isoforms, modern concepts on the catalytic and regulatory
      centers of the enzyme are presented. The role of heme and sulfhydryl groups in
      the functioning of guanylate cyclase and the significance of the nitrosyl-heme
      complex formed as a result of interaction of guanylate cyclase heme with NO are
      analyzed. Using new approaches for studying the antihypertensive and
      antiaggregatory actions of nitric oxide in combination with the newly obtained
      data on the regulatory role of guanylate cyclase in the platelet aggregation
      process, the most important results were obtained. The priority data on the new
      inhibitors of nitric oxide-dependent guanylate cyclase activation (among which
      turn to be the drugs) and the possible molecular mechanism of their
      pharmacological action are presented.

PMID- 12068498
TI  - [Catecholamines: biochemistry, pharmacology, physiology, clinical aspects].
AB  - Catecholamines (CAs) realise activity of certain cerebral neurons,
      sympathoadrenal system and peripheral cells producing dopamine. CAs control
      metabolism, template biosynthesis, cytological, physiological and psychological
      processes. During recent 10-15 years complex employment of various
      interdisciplinary approaches (including molecular biology techniques) resulted in
      some important achievements. Cellular transporters and 10 individual receptors
      were discovered and studied. Basic mechanisms of CA signal transduction into
      nucleus and mitochondria, regulation of gene expression, hyperplasia, hypertrophy
      and biological oxidation have been recognised. It was found that besides central
      neurotransmitter action DA also acts as peripheral auto- and paracrinic hormone.
      CA participate in pathogenesis of many illnesses and in the defence mechanisms of
      a body. CA and related substances are effective and widely used drugs.

PMID- 12068499
TI  - [What induces cell death: caspases or mitochondria?].

PMID- 12068500
TI  - [Study of the tissue and subcellular distribution of isatin-binding proteins with
      optical biosensor].
AB  - An original method for the integral evaluation of tissue and subcellular
      distribution of isatin binding proteins has been developed. This method is based
      on continuous monitoring of changes of optical characteristics that accompany
      complex formation between a ligand (immobilized on dextran bed of IAsys biosensor
      cell) and its soluble receptor. Solubilisation of tissue preparations and
      subcellular fractions with detergent (1% Triton X-100) is the important
      preconditions for the applicability of this method. The immobilisation of 5
      aminoisatin was achieved by peptide bond formation between amino group of this
      isatin analogue and carboxyl group of the dextran bed of the biosensor cell.
      Addition of Triton X-100 treated preparations of membrane and soluble fractions
      of rat brain, liver, heart, and kidneys to the biosensor cell resulted in
      appearance of the characteristic response, indicating complex formation with the
      immobilised isatin analogue. The magnitude and a shape of kinetic curve vary in
      these samples. Isatin binding proteins predominated in membrane fractions of
      brain, liver and heart preparations whereas in the kidneys the highest isatin
      binding response was detected in the soluble fraction. The distribution of isatin
      binding sites in the particulate fraction reduced in the following order:
      brainstem > brain hemispheres = cerebellum > heart > kidneys > liver. In the
      soluble fraction there was different rank of isatin binding activity: kidneys >
      heart > brainstem = brain hemispheres > liver > cerebellum. Liver outer
      mitochondrial membranes are characterised by the higher isatin-binding than
      mitochondria. Treatment of mitochondria with clorgyline and deprenyl,
      specifically inhibiting MAO A and B, respectively, significantly reduced the
      magnitude of the biosensor response and changed the shape of the kinetic curve.
      These data are consistent with the notion that within mitochondria MAOs are the
      major targets of isatin.

PMID- 12068501
TI  - [Determination of fractional and subfractional blood lipoprotein compositions
      with small angle X-ray scattering (a comparison with a biochemical method)].
AB  - Highly accurate and fast method for determination of quantitative and qualitative
      compositions of serum lipoprotein (LP) fractions and subfractions, using small
      angle X-ray scattering on the "Siemens" difractometr, has been developed. The
      method allows to determine the concentrations of serum cholesterol (CH),
      triglycerides (TG), high-density lipoprotein (HDL)-CH, low-density lipoprotein
      (LDL)-CH, phospholipides (FL) and total lipids. It allows to determine the levels
      of CH, TG, FL in LP subfractions and concentrations of 5 very-low-density
      lipoprotein, intermedius-density lipoprotein, 3 LDL (large, intermedius and small
      dense particles) and 5 HDL subfractions. The method is based on the elaborated
      united model of all LP fractions and subfractions as a result of generalization
      and analysis of literature data about LP composition and size. New method was
      proved to be highly reproductive. Strong positive correlation exists between
      serum levels of CH, TG, HDL-CH determined by enzymatic biochemical and our
      methods. The method is simple to perform and of high diagnostic value, and can,
      therefore, be applied to clinical purposes.

PMID- 12068502
TI  - [Introduction of biologically active fragments of interferon-alpha2 and insulin
      into the artificial protein albebetin affects immunogenicity of the final
      construct].
AB  - The immunogenicity of the artificial protein albebetin and its derivatives with
      active peptide fragments was investigated. We also studied the influence of the
      peptides on the immunogenicity of the whole construct and contribution of each
      component to the immunogenicity. Two of three studied proteins contained active
      peptides from human IFN-alpha and insulin. Three continuous antigenic sites with
      different immunogenic potential were recognized in the chimerical proteins. The
      interferon fragment was the immunodominant site in the albeferon and albeferon
      insulin molecules, while the insulin fragment displayed low immunogenic activity.
      All continuous B-epitopes are located at the boundaries of the secondary
      structure elements and at the predicted surface-located sites of albebetin
      molecule. Thus, peptide fragments attached to the artificial protein carrier can
      influence immunogenicity of the resulting construct.

PMID- 12068503
TI  - Bioterror drills show need to revise emergency preparedness plans.

PMID- 12068504
TI  - QI project improves patient outcomes.

PMID- 12068505
TI  - Happy employees mean satisfied patients.

PMID- 12068506
TI  - Simple solution: clinical training for entire staff.

PMID- 12068507
TI  - Improve your discharge planning effectiveness.

PMID- 12068508
TI  - Bioterrorism watch. They don't call it bioterror for nothing: fear is the foe
      when anthrax spores are found within hospital walls.

PMID- 12068509
TI  - Bioterrorism watch. APIC: smallpox plan uses outdated infection control.

PMID- 12068510
TI  - The real barrier in hearing protection is indifference.

PMID- 12068511
TI  - Does online training live up to its promises?

PMID- 12068512
TI  - Safety incentives. Why these programs work.

PMID- 12068513
TI  - Proactive pursuits.

PMID- 12068514
TI  - Oh, my aching back!

PMID- 12068515
TI  - Mechanically motivated. A systematic approach can overcome the challenges of
      implementing engineering solutions in material handling activities.

PMID- 12068516
TI  - Measures of success. Looking beyond incident rates helps uncover critical
      elements bridging the gap to a safe, productive workplace.

PMID- 12068517
TI  - The hidden value of safety. Are accident costs really like icebergs?

PMID- 12068518
TI  - National Safety Month in focus. The final spotlight in this annual four-week
      observance shines on workplace safety.

PMID- 12068519
TI  - Signs & signals.

PMID- 12068520
TI  - NCHRP 350: a crash course on crashworthiness.

PMID- 12068521
TI  - Pointing a finger at the hazards of gloves.

PMID- 12068522
TI  - Needs assessment for AEDs.

PMID- 12068523
TI  - Multi-modal mishaps. A new manual and related research shows why and how
      companies should streamline multi-modal shipping.

PMID- 12068524
TI  - Hearing protection. Construction noise strategies.

PMID- 12068525
TI  - Hearing conservation in industry.

PMID- 12068526
TI  - Construction safety. PPE that makes a visible difference.

PMID- 12068527
TI  - Stop the sacrifices.

PMID- 12068528
TI  - Creating effective learning environments.

PMID- 12068529
TI  - [Liver transplant in hepatocellular carcinoma: would the organ shortage and good
      outcome justify the expansion of indication or of new surgical techniques?].

PMID- 12068530
TI  - [Results of liver transplantation in patients with hepatocellular carcinoma].
AB  - BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies
      worldwide. Liver transplantation has emerged as a good option for early-stage
      hepatocellular carcinoma yielding survival rates as good as for recipients
      without this type of tumor. OBJECTIVE: To assess the outcome of cirrhotic
      patients with hepatocellular carcinoma undergoing liver transplantation at the
      Liver Transplantation Service of the "Hospital de Clinicas", Federal University
      of Parana, Curitiba, PR, Brazil. METHODS: Retrospective study of cirrhotic
      patients with hepatocellular carcinoma undergoing orthotopic liver
      transplantation at the mentioned Institution between September 1991 and September
      2000. The diagnosis of hepatocellular carcinoma was established during the
      pretransplant workup in five patients and the tumor was an incidental finding in
      the native liver in three. The indication for liver transplantation was
      restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with
      each nodule measuring less than 3 cm, and no evidence of vascular invasion or
      extrahepatic spread. Patient survival and evidence of tumoral recurrence
      posttransplant were evaluated. RESULTS: The most common cause for
      pretransplantation liver disease was hepatitis C virus (50%). On examination of
      the explanted liver, the majority of patients (6/8, 75%) had a single lesion; one
      patient had two nodules and one had a multifocal hepatocellular carcinoma found
      incidentally in the native liver. Tumor size ranged from 0.2 to 5.0 cm. All cases
      had neither vascular invasion nor linfonodal envolvement. All patients remained
      alive and free of tumor recurrence at the time of the study with a mean follow-up
      of 18.5 months (range, 5-29 months). CONCLUSION: Liver transplantation is a good
      therapeutic option for early stage hepatocellular carcinoma arising in cirrhotic
      patients. With proper selection, liver transplantation can offer excellent
      survival rates free of tumor recurrence.

PMID- 12068531
TI  - [Patent paraumbilical vein: hemodynamic importance in Mansoni's hepatosplenic
      portal hypertension (Study with ultrasonography Doppler].
AB  - BACKGROUND: The hemodynamical effect of the collateral portosystemic circulation
      upon the portal system has not yet been fully understood. The US-Doppler made
      possible the non-invasive study of the portal system by evaluating the
      parameters: flow direction, diameter and flow velocity in it's vessels. AIMS: To
      study the paraumbilical vein as a collateral portosystemic pathway and identify
      patterns for appraising its hemodynamic importance to the portal system. METHOD:
      US-Doppler study of the portal system of 24 patients with Mansoni's hepatosplenic
      schistosomic portal hypertension, previous esophagic variceal bleeding and patent
      paraumbilical vein with hepatofugal flow. The diameter and the mean flow velocity
      were measured in the paraumbilical vein and so were the mean flow velocity in the
      portal vein, right and left portal branches. The Pearson test (linear
      correlation) was applied to the portal vein's mean flow velocity and the
      paraumbilical vein's diameter and mean flow velocity. The patients were divided
      in four groups: D1-paraumbilical vein with diameter < 0.68 cm (n = 14), D2
      paraumbilical vein with diameter > or = 0.68 cm (n = 10), V1-paraumbilical vein
      with mean flow velocity < 18.41 cm/seg (n = 13) and V2-paraumbilical vein with
      mean flow velocity > or = 18.41 cm/seg (n = 11). The mean flow velocity in the
      portal vein, right and left portal branches of the four groups were compared.
      RESULTS: The paraumbilical vein diameter was 0.68 +/- 0.33 cm (range: 0.15-1.30
      cm) and the mean flow velocity was 18.41 +/- 11.51 cm/seg (range: 5.73-38.20
      cm/seg). The linear correlation between the portal vein's mean flow
      velocity/paraumbilical vein diameter and the paraumbilical vein's mean flow
      velocity showed r = 0.504 and r = 0.735, respectively. In the group D2 there was
      an increase in the mean flow velocity in the portal vein (17.80 +/- 3.42/22.30 +/
      7.67 cm/seg) and in the left portal branch (16.00 +/- 4.73/22.40 +/- 7.90
      cm/seg). In the group V2 there was an increase in the mean flow velocity in the
      portal vein (16.31 +/- 3.49/21.96 +/- 5.89 cm/seg) and in the left portal branch
      (14.22 +/- 4.41/21.94 +/- 7.20 cm/seg). There was no change in the right portal
      branch (13.67 +/- 5.74/15.43 +/- 3.43 cm/seg). CONCLUSIONS: In portal
      hypertension due to hepatosplenic schistosomiasis, the patent paraumbilical vein,
      with hepatofugal flow, diameter > or = 0.68 cm and mean flow velocity > or =
      18.41 cm/seg causes an increase of the mean flow velocity in the portal vein and
      left portal branch. The best US-Doppler parameter to appraise the paraumbilical
      vein influence upon the portal system is the mean flow velocity. The correlation
      between the increase in portal vein's mean flow velocity is stronger with the
      paraumbilical vein's mean flow velocity than with its diameter. The increase in
      the portal vein's and left portal branch's mean flow velocity may be understood
      as the paraumbilical vein's hemodynamic influence upon the portal system. An
      active portosystemic collateral pathway increases the mean flow velocity in the
      vein's segment proximal to its point of origin.

PMID- 12068532
TI  - Gastric stump mucosa: is there a risk for carcinoma?
AB  - BACKGROUND: Patients who underwent partial gastric resections are at an increased
      risk for the development of cancer in the gastric remnant. AIM: To assess the
      long-term patients who underwent surgical treatment for peptic ulcer disease
      through endoscopic and pathologic evaluation of the gastric stump mucosal
      alterations. PATIENTS AND METHODS: Between 1987 and 1990, 154 patients (mean =
      20.4 years after gastrectomy) were evaluated by upper digestive endoscopy with
      multiple biopsies and pathological examination. RESULTS: Endoscopic alterations
      were present in 111 patients (72.1%). The commonest pathologic alterations were
      foveolar hyperplasia, intestinal metaplasia and cystic dilation. Severe dysplasia
      was noted in two (1.25%) and carcinoma in 13 (8.4%) of the cases. In four
      patients (3.8%) the endoscopic findings did not show any evidence of tumors,
      however they were detected due to multiple biopsies and histologic studies.
      CONCLUSIONS: Surveillance of these patients with endoscopy and multiple biopsies
      may provide the means to diagnose tumors at an early stage, but the cost benefit
      ratio of surveillance requires further study.

PMID- 12068533
TI  - [Celiac disease: evaluation of compliance to gluten-free diet and knowledge of
      disease in patients registered at the Brazilian Celiac Association (ACA)].
AB  - BACKGROUND: The compliance to a gluten-free diet may prevent the development of
      both non-malignant and malignant complications. AIM: To evaluate compliance to a
      gluten-free diet and knowledge of the disease in celiac patients registered at
      the Brazilian Celiac Association (BCA). METHODS: A structured questionnaire was
      designed to assess compliance to a gluten-free diet as well as knowledge of the
      celiac disease. It was mailed to 584 members of BCA. RESULTS: Five hundred and
      twenty nine (90.6%) of a total of 534 (91.4%) answered questionnaires were
      analyzed; 69.4% were classified as compliant patients whereas 29.5% were
      classified as noncompliant. The proportion of patients age 21 or older who
      consume gluten frequently or without any restriction is larger (17.7%) than those
      who were younger than 21 years (9.9%). Frequency of dietary compliance was higher
      when the diagnosis had taken less than 5 years to be established; 82% of the
      patients replied that the small intestine was the part of the body affected by
      the disease. The most common symptoms of the disease according to the answers
      were diarrhea (96.6%), weight loss (93.4%), protuberant abdomen (90.4%), anemia
      (68.1%) and vomiting (59.6%). Only 59.0% agreed with the existence of genetic
      predisposition; 90.4% answered that the disease is permanent and 96.2% stated
      that the diet should exclude gluten absolutely; 67.1% answered that the gluten is
      a protein and according to 92.1% questionnaires this protein is present in wheat,
      rye, barley and oat. Greater compliance was observed when there was an
      understanding of the disease and diet. The small intestine biopsy was considered
      necessary for just 67.5% of the patients, and greater compliance was observed in
      patients who had undergone at least one small intestine biopsy. CONCLUSION: Our
      findings indicate that the more the patients know and understand about the
      disease, the better able they are to comply with the diet.

PMID- 12068535
TI  - Recurrent and de novo non-alcoholic steatohepatitis following orthotopic liver
      transplantation.
AB  - BACKGROUND: Non-alcoholic steatohepatitis was coined in 1980 to describe
      pathological and clinical features of non-alcoholic disease associated with
      pathological features, commonly seen in alcoholic-liver disease itself. It is now
      a well-recognised cause of end-stage liver disease and a rare cause of orthotopic
      liver transplantation. A small number of cases with recurrent non-alcoholic
      steatohepatitis following liver transplantation have been reported, however de
      novo non-alcoholic steatohepatitis in the liver allograft is not well recognised.
      AIMS/RESULTS: We report four cases of non-alcoholic steatohepatitis following
      orthotopic liver transplantation describing the factors related with the
      pathology. The recurrence of fatty infiltration occurred within 21 months and
      transition from mild steatosis to non-alcoholic steatohepatitis and early
      fibrosis was observed within 60 months post transplant in all four patients. All
      four cases had association with one or multiples risk factors (obesity, type 2
      diabetes and/or hyperlipidemia). CONCLUSIONS: Management of this risk factors may
      play a therapeutic role in the prevention of recurrent and de novo non-alcoholic
      steatohepatitis following orthotopic liver transplantation.

PMID- 12068534
TI  - Detection of Helicobacter pylori in gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: Considering the high prevalence of stomach cancer in
      the northern region of Brazil and the recognized relationship between chronic
      gastric inflammation caused by Helicobacter pylori, and its carcinogenic
      potential, the objective we had with this study was to investigate the presence
      of the microorganism in macro and microscopic presentations of neoplasm in
      different regions of the stomach, and in non-malignant lesions concomitant to the
      adenocarcinoma in patients originating from the metropolitan area of Belem (State
      of Para, Brazil). METHODS: Examinations were made on 172 patients divided into
      two groups: group I, formed by 75 patients with gastric carcinoma, and group II,
      formed by 97 patients with mild enanthematic gastritis, considered control group.
      The diagnosis was obtained during endoscopic examination and the respective
      biopsy. Gastric neoplasms were classified macroscopically in accordance with
      Borrmann's classification, and microscopically in accordance with Lauren's
      classification. In group I, 54 patients were male and 21 female while in group
      II, 22 patients were male and 75 female. The average age in group I was 61.2
      years (range 27 to 86 years), while in group II it was 37.5 years (range 16 to 69
      years). Thin sections were prepared and stained using the hematoxylin-eosin
      method. In the Helicobacter pylori research, the modified Gram stain was
      utilized. Statistical analysis was done by utilizing the chi-squared (chi 2)
      test, Mann-Whitney test (U), and Fisher's exact test. RESULTS: The results showed
      the detection of Helicobacter pylori were significantly greater in patients with
      mild enanthematic gastritis than in patients with gastric carcinoma. The presence
      of Helicobacter pylori in patients with gastric carcinoma and mild enanthematic
      gastritis was significantly greater in the antral region than in other gastric
      regions. Helicobacter pylori detection in patients with gastric carcinoma did not
      present a significant difference in relation to the macroscopic aspect of the
      tumor either intestinal or diffuse histological types. CONCLUSIONS: These data
      suggest the presence of the bacteria is predominant in the antral region and it
      does not show relation with the macroscopic types or histological intestinal or
      diffuse types of gastric carcinoma.

PMID- 12068536
TI  - [Thyroid function tests in viral chronic hepatitis].
AB  - BACKGROUND: One hundred and twenty five patients with virus B or C chronic active
      hepatitis and postnecrotic cirrhosis and different degrees of liver dysfunction
      were studied. AIM: 1) To determine a thyroid hormonal profile; 2) to evaluate the
      prognostic value of these tests in relation to the progression of the disease and
      mortality; 3) compare these findings with Child-Pugh classification. PATIENTS AND
      METHODS: The patients were divided in four groups: a) 31 with chronic active
      hepatitis; b) 41 with postnecrotic cirrhosis Child A; c) 35 with postnecrotic
      cirrhosis Child B and d) 18 with postnecrotic cirrhosis Child C. The protocol
      comprised serum measurements of albumin and bilirrubin, estimates of prothrombin
      time and clinical evaluation of ascites and encephalopathy, measurement of total
      serum triiodothyronine, thyroxine, thyroid-stimulating hormone, free thyroxine,
      reverse triiosothyronine, calculated rT3/T3 index (IrT3) and thyrotropin
      releasing hormone test. RESULTS: Total serum triiodothyromnine showed the most
      significant difference among the groups, gradually lower as the disease became
      more advanced (CAH: 149.2 +/- 42.3 ng/dL; PNC-A: 137.4 +/- 37.2 ng/dL; PNC-B:
      88.0 +/- 28.4 ng/dL and PNC-C: 41.8 +/- 21.9 ng/dL). Low levels of T4 (4.5 +/-
      2.0 micrograms/dL) and FT4 (0.7 +/- 0.4 ng/dL) and elevated levels of thyroid
      stimulating hormone (7.2 +/- 11.5 microIU/mL), reverse triiosothyronine (60.8 +/-
      52.1 ng/dL) and calculated rT3/T3 index (2.2 +/- 2.6) were more frequent in
      patients with postnecrotic cirrhosis Child C. Thyrotropin-releasing hormone test
      was normal in the majority of the patients. CONCLUSION: The present study shows a
      positive relationship between the low serum levels of T3 and elevated serum
      levels of rT3 and IrT3/T3 with the degree of hepatic dysfunction according to the
      Child-Pugh classification.

PMID- 12068537
TI  - [Intestinal absorption of D-xylose in children infected with the human
      immunodeficiency virus].
AB  - AIM: To evaluate the intestinal absorption in HIV-infected children children 14
      months to 14 years and to investigate its relationship to diarrhea, nutritional
      status, immune dysfunction, classical enteric parasites and Cryptosporidium.
      METHODS: Intestinal absorption was investigated by measuring serum D-xylose.
      Fecal samples were investigated for classical pathogens and Cryptosporidium. The
      sample size was calculated considering a 30% prevalence of altered D-xylose
      absorption in HIV-infected children with a 5% accuracy. Statistical procedures
      used were: descriptive measurements, multiple correspondence analysis and
      logistic regression. RESULTS: D-xylose absorption was altered in only 8 out of
      104 (7.7%) and Cryptosporidium was positive in 33 out of 104 (31.73%) HIV
      infected children. The multiple correspondence analysis suggested an association
      between an altered D-xylose test and Cryptosporidium. D-xylose malabsorption was
      not associated with diarrhea, nutritional status, immune disfunction and classic
      enteric parasites. CONCLUSIONS: Intestinal malabsorption evaluated through the D
      xylose test was an uncommon finding in HIV-infected children. Intestinal
      dysfunction when present seems to be related to Cryptosporidium, but not to
      diarrhea, nutritional status, immune disfunction and classic enteric parasites.

PMID- 12068538
TI  - [New concepts in nutrition: considerations on the connection diet-health].
AB  - The physiological effects of several foods are discussed as possible factors
      reducing the risk of degenerative diseases as cardiovascular and some cancers.
      The new emmerging concept of functional foods is presented with examples as the
      phytoestrogens of soya beans. The importance of consuming olive oil is emphatic,
      but with criticism to the lost of physiological bioactive material during the
      normal extractions of the olive oil and the refinement. So, much attention is
      needed. The way to obtain much of these bioactive protectors foods is summarized.

PMID- 12068539
TI  - [Causes of malnutrition in post-gastrectomy patient].
AB  - BACKGROUND: The stomach through its mechanical and chemical processes has an
      unique role in the food processing and bioavailability. Hence gastrectomy has
      predictable and modifiable nutritional consequences depending upon its knowledge
      and the post-surgery therapies. OBJECTIVE: To point out the impact of gastrectomy
      on the nutritional status focusing on both mechanical and chemical actions of
      stomach on intaked foods. RESULTS: The protein-energy malnutrition and consequent
      body-weight loss follow reversely the remainer gastric volume and post-operatory
      length and have anorexy and intestinal malabsorption as their main causes. Lower
      food intake is probably due to either emotional factors or chemical mediators
      acting centrally on hypothalamus. The diarrhea may be due to either increased
      peristalsis or bacterial overgrowth both aggravated by exocrine-pancreas
      deficiency and gallbladder overflow. The intestinal malabsorption leading to
      fecal losses of fat and or nitrogen as well as lower utilization of dietary
      calcium and liposoluble vitamins. The gastrectomy-related anemia is consequent to
      lower secretion of both HCl and intrinsic factor leading to a decreased
      solubilization of iron and lower absorption of vitamin B12, respectively.
      CONCLUSION: Body-weight loss and anemia are the protein-energy malnutrition
      findings often found in these patients whose severity and lasting depend upon the
      type of surgery, post-surgery length and received nutritional care, being
      strongly recommended a supervisioned dietary care.

PMID- 12068540
TI  - [Esophageal manometry: equipment cleaning and disinfection with glutaraldehyde].
AB  - BACKGROUND: Many publications have emphasized the need of proper cleaning,
      disinfection and sterilization process for reused materials intended to prevent
      cross infections. As the endoscope the esophageal manometry catheters are
      considered as semicritical materials and must be free of microrganisms. AIM: To
      standardize the esophageal manometry materials cleaning and disinfection process
      to guarantee the safety of patients when reusing semicritical materials. It was
      based on international protocols and according to recommendations of the Hospital
      Infection Control Commission of the "Hospital de Clinicas de Porto Alegre", Porto
      Alegre, RS, Brazil. MATERIALS AND METHODS: Enzymatic detergent was used for
      catheter cleaning, followed by immersion with 2% glutaraldehyde solution during
      20 minutes for high-level disinfection. The water reservatory was kept clean and
      dry to prevent microorganisms proliferation. CONCLUSIONS: The high level
      disinfection with 2% glutaraldehyde, preceded by enzymatic detergent cleaning, is
      a safe and simple technique that avoids cross infection in the esophageal
      manometry equipment. This care must be taken after each manometric procedure. The
      transducers must be resterilized in ethylene oxide. The professionals of this
      area must work in concordance with the Hospital Infection Control Commission,
      being acquainted with the country laws and regulations and keeping sterilizing
      process and materials updated.

PMID- 12068541
TI  - [Genome radiation hybrid mapping: summary and future directions].
AB  - Genome mapping by means of radiation-induced interspecific cell hybrids is a
      direct way to localize both high- and low-polymorphic nucleotide sequences,
      including gene sequences, on animal chromosomes. Using radiation hybrid panels
      either individual chromosomes and loci or entire genome can be mapped. This
      efficient approach makes it possible to reach high resolution of markers (up to
      100 bp) as well as unify the mapping language. Due to electronic means of
      communication, the same experimental material can be used in numerous
      laboratories to provide high-resolution extended genomic maps saturated with
      markers. Radiation hybrid mapping is a powerful tool for analysis of complex
      genome structure. Using radiation hybrid maps permitted verification of regions
      of chromosome homeology in various species and detection of regions with
      conserved sequence and conserved gene order. Identification of these regions is
      extremely important for understanding evolution of species karyotypes and for
      making use of positional cloning to isolate genes responsible for commercial
      traits as well as genes involved in hereditary human diseases.

PMID- 12068542
TI  - [Chromatin diminution is a key process explaining the eukaryotic genome size
      paradox and some mechanisms of genetic isolation].
AB  - The functions of redundant (junk, selfish, parasitic, etc.) DNA in eukaryotes can
      be reliably inferred from chromatin diminution (programmed elimination of up to
      94% of the genome from somatic germ cells in Ascaris and Cyclops). These
      functions should be sought in germ cells, where this DNA is preserved during the
      entire life time of the species. A possible biological role of redundant DNA as a
      factor disrupting meiotic chromosome synapsis is suggested. At the same time,
      chromatin diminution itself can act as a mechanism of postzygotic isolation. All
      stage of the complex diminution mechanism could not be fixed in the genetic
      program of the species via gradual accumulation of mutations. The "program" of
      diminution must have appeared at once and in the completed form.

PMID- 12068543
TI  - [Jumping gene gs of Lycopersicon lycopersicum (L.) Karsten ex Farw].
AB  - Studies on tomato culture revealed for the first time two phenomena: (1)
      instability of gene gs (green stripes on fruits) and (2) spontaneous expression
      of the character determined by the gs gene without involvement of sexual
      reproduction in some cultivars. The instability of the gs gene was detected by
      the phenotypic expression of character in different plants from the same strain,
      racemes of the same plant, fruits of the same raceme, and parts of the same
      fruit. The instability of the gs gene may be determined by endogenous regulatory
      genetic elements causing specific changes of the character, with the degree of
      these changes varying for different parts of the fruit and places of its
      formation on the plant. The instability of the gs gene was expressed for four
      generations. There were no other phenotypic changes in the offsprings studied. In
      addition, migration of the recessive gs gene to other cultivars followed by its
      complete expression in a whole plant or some parts of the plant was observed.
      Exogenous transfer of the gs gene is suggested.

PMID- 12068544
TI  - [Formation of an additional promotor in the regulatory region of the Escherichia
      coli udp gene and its structural and functional characterization].
AB  - Structural and functional organization of the mutant udpP18 promoter generated
      after the spontaneous deletion of the G base in the -79 position relative to the
      start site of transcription from the main (P1) promoter within the regulatory
      region of the udp gene was studied. In this mutant, a new, functionally active
      promoter (P2) with the start site of transcription in the -64 position that
      contained the typical motif 5'-TG-3' located in front of the Pribnow sequence was
      formed. The data presented suggest that the expression of the P2 promoter, unlike
      that of P1, is not subjected to regulation with participation of the CytR protein
      and the cAMP-CRP complex. Results of mutational analysis of the P2 promoter
      showed that substitutions of the nucleotide G in the -14 position and nucleotide
      T in the -15 position significantly diminish the level of transcription from the
      P2 promoter. On the basis of these data, it is concluded that the P2 promoter
      could be assigned with respect to its characteristics to a group of promoters
      with an extended -10 region. The synergistic effect of P1 and P2 promoters on
      total expression of the udp gene in the mutant udpP18 was detected.

PMID- 12068545
TI  - [Isolation and genetic study of Erwinia mutants devoid of common components of
      the phosphoenolpyruvate-dependent phosphotransferase system].
AB  - Mutants of bacteria belonging the genus Erwinia (Erwinia chrysanthemi and Erwinia
      carotovora) with pleiotropic disturbances in the utilization of many substrates
      were obtained through chemical and transposon mutagenesis. Genetic studies
      revealed that these mutants had defective ptsI or ptsH genes responsible for the
      synthesis of common components of the phosphoenolpyruvate-dependent
      phosphotransferase system, enzyme I and the HPr protein, respectively. The ptsI+
      allele in both Erwinia species was cloned in vivo. Mapping of obtained mutations
      indicated that the ptsI and ptsH genes of E. chrysanthemi do not constitute a
      linkage group. The ptsI gene is located at 100 min of the chromosomal map,
      whereas the ptsH gene is located at 175 min. Sequencing of a portion of the E.
      chrysanthemi ptsI gene showed that a product of the cloned DNA region had up to
      68% homology with the N terminus of Escherichia coli enzyme I.

PMID- 12068546
TI  - [The detection of genome polymorphism in Stachys species using RAPD].
AB  - Molecular genome analysis was for the first time carried out in the genus
      Stachys. RAPD analysis proved to be suitable for identifying the species-specific
      markers, studying the interspecific DNA polymorphism, and detecting the genetic
      changes that arise during in vitro culturing of Stachys sieboldii. In addition,
      RAPD was used for screening genetic variation in S. sieboldii regenerants
      obtained at various phytohormone concentrations. High cytokinin concentrations
      and multiple regeneration were shown to induce genetic changes detectable with
      RAPD patterns. High DNA polymorphism was demonstrated for two types of S.
      sieboldii callus cultures and for plants regenerated from a callus culture.

PMID- 12068547
TI  - [Intrapopulation variability of some meadow plant species with respect to their
      ability to accumulate 90Sr].
AB  - Field and laboratory studies of different plant species revealed the presence of
      intraspecific polymorphism in respect of the ability to accumulate 90Sr. The
      populations consisted of the plants effectively and ineffectively accumulating
      90Sr; the former were capable of two to thirty-seven times higher accumulation
      than the latter. The proportion of the plants with high accumulating ability can
      reach 10%. Judging by the high values of the coefficients of correlation between
      the laboratory and field data, the results of the 90Sr content analysis different
      plant species were highly concordant. Accumulation of 90Sr by plants is in direct
      relation to its content in soil, but within the limits of the same contamination
      density, and is controlled by the plant genotype.

PMID- 12068548
TI  - [Instability of the ploidy level in autotetraploid sorghum plants from a line
      with variable male fertility].
AB  - It was found that, in some of the plants in generations C1-C5 of induced
      tetraploids in the semisterile sorghum line AS-1-30, more than 30% of pollen
      grains (PGs) have sizes typical of haploid PGs. Pollen of these plants was used
      to pollinate different lines of sorghum with cytoplasmic male sterility (CMS).
      Diploid hybrids were obtained, which confirms the presence of haploid PGs in the
      tetraploids studied. When tetraploid plants with an increased frequency of
      haploid PGs were pollinated with pollen of plants from fertile diploid lines,
      diploid hybrids were also obtained. This demonstrates that the tetraploids
      studied had haploid ovicells. In generation C4, a chimeric plant was found; one
      of its shoots was diploid (judging from morphological characters) and produced as
      many as 99% of haploid PGs. It is assumed that haploid gametes in autotetraploids
      are formed through somatic reduction of chromosomes at different ontogenetic
      stages.

PMID- 12068549
TI  - [Expression of CMS in zygotic and apozygotic progenies of sugar beet Beta
      vulgaris L].
AB  - Zygotic and apozygotic progenies of sugar beet exhibit high phenotypic variation
      with respect to cytoplasmic male sterility (CMS). There are progenies with
      completely sterile, semisterile, semifertile, and fertile pollen. The proportions
      of semifertile and fertile plants in zygotic and apozygotic progenies varied from
      zero to 28% and from zero to 17.8%, respectively. Comparison of the phenotypic
      distributions in zygotic and apozygotic progenies did not reveal significant
      differences in the CMS expression, although the latter is determined by the
      maternal S-plasmotype and both maternal and paternal (pollinator) genotypes in
      zygotic progenies and only by the maternal S-plasmotype and genotype in
      apozygotic progenies. It has been hypothesized that the instability of the CMS
      expression in apozygotic progenies is determined by epigenetic variation in the
      activities of the genes that control the maintenance of the pollen-grain
      sterility. Inactivated dominant alleles Rf1(0) and Rf2(0) in homozygous state may
      function as sterility maintenance genes, whereas activation of these alleles
      during ontogeny results in a partial or complete restoration of pollen-grain
      fertility. It was demonstrated that pollen fertility of mother plants with S
      cytoplasm did not affect the CMS expression in two sib progenies. Conversely, in
      two other progenies, the proportion of fertile plants was significantly higher in
      the sib progenies of mother plants with fertile pollen and S cytoplasm
      (inheritance of epigenetic variation).

PMID- 12068550
TI  - [Gene-geographical variation and genetic differentiation in red-backed voles of
      the genus Clethrionomys (Rodentia, Cricetidae) in the Okhotskii region].
AB  - Thirteen enzyme systems and three nonenzyme proteins were electrophoretically
      analyzed in red-backed voles of the genus Clethrionomys. In total, 25 loci were
      interpreted. Gene-geographic variation was studied and indices of genetic
      variability and differentiation were determined. By the distribution of
      electrophoretic variants of hemoglobin, C. rutilus was shown to be divided into
      two geographical groups (northern and southern). A low level of genetic
      differentiation was revealed in the island isolates of C. rutilus and C.
      rufocanus. Separation of C. rufocanus, C. rex, and C. sicotanensis into a
      superspecies complex was confirmed. A study of differential G- and C-banding on
      C. rutilus and C. rufocanus chromosomes did not reveal intraspecific variation of
      autosomes. In these species, karyotypes of voles from Kamchatka Peninsula were
      studied for the first time. They appeared to be morphologically similar to the
      karyotypes continental voles by both autosomes and sex chromosomes.

PMID- 12068551
TI  - [Distribution of the ABO blood groups and the HP, TF, GC, PI and C3 serum
      proteins in Yakuts].
AB  - In Yakut populations examined, polymorphisms of immunological and serum protein
      markers, including AB0 and Rhesus blood groups, HP, TF, GC, PI and C3, were
      revealed. Gene frequencies for the systems studied fell into the following
      ranges: AB0 system: r, 0.514 to 0.663; p, 0.136 to 0.306; q, 0.110 to 0.337;
      haptoglobin HP*1: 0.214 to 0.431; transferrin TF*C: 0.700 to 1.0; group specific
      component GC*1: 0.821 to 0.978; PI*M1 proteinase inhibitor (or alpha 1
      antitrypsin) PIM1: 0.860 to 0.946; and third component of the complement C3*F:
      0.031 to 0.143.

PMID- 12068552
TI  - [Allele polymorphism of the serotonin transporter gene and clinical heterogeneity
      of depressive disorders].
AB  - Depression disorders are a clinically heterogeneous disease group. Their
      development is to a substantial extent underlain by dysfunction of the serotonin
      system, in particular, disturbed serotonin transport. The heterogeneity of
      depressions is associated, among other factors, with the age at disease onset.
      Allele polymorphism of the serotonin transporter (5-HTT) gene was tested for
      association with age at disease onset, clinical signs, and anxiety-related traits
      of depression patients. A sample included 77 patients (mean age 61.2 +/- 8.8
      years) with late-onset depression (LOD, mean age at onset 56.58 +/- 9.7 years)
      and 74 patients (mean age 31.0 +/- 11.8 years) with early-onset depression (EOD,
      mean age at onset 23.9 +/- 7.4 years). In genotype frequency distribution of two
      5-HTT gene polymorphism, the LOD and EOD groups did not differ from each other
      (chi 2 = 0.33, P = 0.85 for VNTR-17; chi 2 = 3.33, P = 0.19 for HTTLPR) and from
      a control group (chi 2 = 0.34, P = 0.84 for VNTR-17; chi 2 = 2.1, P = 0.35 for
      HTTLPR). In either group, patients differing in VNTR-17 and HTTLPR genotypes did
      not differ in psychological traits and, in particular, in anxiety-related traits.
      In the case of the HTTLPR polymorphism, LOD patients with genotype ss tended to
      display less severe neuroticism (t = 2.03, P = 0.0507) and scored significantly
      less on the Hamilton depression scale (t = 2.19, P = 0.039). Thus, the 5-HTT gene
      polymorphisms do not affect the risk of depression but is possibly associated
      with specific clinical signs of the disease, at least in elderly patients.

PMID- 12068553
TI  - [Estimation of the recombination fraction by the maximum likelihood method in
      mapping interacting genes relative to marker loci].
AB  - For mapping nonlinked interacting genes relative to marker loci, the
      recombination fractions can be calculated by using the log-likelihood functions
      were derived that permit estimation of recombinant fractions by solving the ML
      equations on the basis of F2 data at various types of interaction. In some cases,
      the recombinant fraction estimates are obtained in the analytical form while in
      others they are numerically calculated from concrete experimental data. With the
      same type of epistasis the log-functions were shown to differ depending on the
      functional role (suppression or epistasis) of the mapped gene. Methods for
      testing the correspondence of the model and the recombination fraction estimates
      to the experimental data are discussed. In ambiguous cases, analysis of the
      linked marker behavior makes it possible to differentiate gene interaction from
      distorted single-locus segregation, which at some forms of interaction imitate
      phenotypic ratios.

PMID- 12068554
TI  - [On the problem of genome redundancy in viruses and prokaryotes].
AB  - A specific index of nucleotide sequence redundancy, the specific restriction
      length of a finite frequency dictionary, was determined for a complete set of
      genes in some viral genomes and a genome of a bacterium, Bacillus subtilis. The
      distribution of the gene number over the specific restriction length was shown to
      be bimodal for viral genomes and unimodal for the Bac. subtilis genome. These
      results agree with earlier data.

PMID- 12068555
TI  - Making the links.

PMID- 12068556
TI  - Afghan health crisis.

PMID- 12068557
TI  - The long view.

PMID- 12068558
TI  - Mum's the word.

PMID- 12068559
TI  - Changes in primary care.

PMID- 12068560
TI  - Head of the queue.

PMID- 12068561
TI  - Build up your defence.

PMID- 12068562
TI  - Are we in it together?

PMID- 12068563
TI  - Spasm control.

PMID- 12068565
TI  - Give us a break.

PMID- 12068564
TI  - Work force.

PMID- 12068566
TI  - A sad step for the 'guardians of normal birth'.

PMID- 12068567
TI  - A multidisciplinary online educational database.
AB  - BACKGROUND: Before the introduction of the Trent online educational database
      there was no central resource that potential purchasers could use to access
      information on clinically relevant courses and programmes of professional
      development. The online database enables cancer centres, cancer units, and
      education and training confederations to identify current provision of cancer
      education and training courses in Trent. CONCLUSION: The electronic online
      evaluation identified that the majority of users felt the information they found
      was relevant and that they would recommend the database to colleagues. They also
      felt that it was easy to find the information they required and the information
      was presented in a useful and appropriate format.

PMID- 12068568
TI  - Getting evidence into practice: ingredients for change.
AB  - Mounting pressure is being exerted to ensure that the delivery of care is
      evidence-based and clinically effective. However, the challenge this presents to
      practitioners is complex. The authors propose that successful implementation of
      evidence into practice is a function of three elements: the nature of the
      evidence; the context in which the change is to take place; and the way the
      process is managed. A framework has been developed to represent these factors.
      For those about to embark on implementation work, this article closes by
      highlighting a number of key questions for consideration, stimulated by the
      framework.

PMID- 12068569
TI  - Loss and bereavement: a nursing response.
AB  - Nurses often have to support people who have suffered loss and bereavement,
      through death of a loved-one or other life events. Sue Read explores the issues
      involved.

PMID- 12068570
TI  - NICE to implement new wound care guidelines.

PMID- 12068571
TI  - Private rooms in hospital 'would hasten recovery'.

PMID- 12068573
TI  - [Superoxide dismutase and catalase activities in carotenoid-synthesizing fungi
      Blakeslea trispora and Neurospora crassa under the oxidative stress].
AB  - The addition of menadione into the medium during cultivation of Neurospora crassa
      in the dark activated its constitutive superoxide dismutase. Exposure to light
      not only activated superoxide dismutase and catalase, but also increased the
      content of neurosporaxanthin. Superoxide dismutase activity in the mixed (+/-)
      mycelium of Blakeslea trispora synthesizing beta-carotene in the dark was much
      lower than that in Neurospora crassa. The superoxide dismutase activity further
      decreased in oxidative stress. The catalase activity decreased with an increase
      in the content of beta-carotene. Our results indicate that neurosporaxanthin
      possesses photoprotective properties in Neurospora crassa. In Blakeslea trispora
      (+/-) fungi, this compound acts as a major antioxidant during inactivation of
      enzymes that detoxify reactive oxygen species.

PMID- 12068572
TI  - [Milk angiogenin (Review)].
AB  - Recent data on angiogenin, a multifunctional member of pancreatic RNase protein
      superfamily, are summarized. Advances in the investigation of angiogenin
      structure, function, and properties are analyzed. Potentialities in natural
      angiogenin production from inexpensive dairy by-products are demonstrated.

PMID- 12068574
TI  - [Dependence of activities of polysaccharide hydrolases and oxidases from Cerrena
      unicolor on the source of carbon and aromatic acids in culture media].
AB  - The activities of carboxymethylcellulase and xylanase in the higher basidial
      fungus Cerrena unicolor grown in avicel-containing medium reached 1.95 and 1.50
      units per mg protein, respectively, whereas in mannitol-containing medium they
      ranged from 0.02 to 0.05 units per mg protein. The activity of fungal beta
      glucosidase depended on the carbon source in the culture medium and ranged from
      2.1 units per mg protein in the presence of mannitol to 17.3 units per mg protein
      in the presence of avicel. In contrast to polysaccharides, easily metabolizable
      substrates (cellobiose, mannitol, and glucose) provided the highest rates of
      secretion of laccase (52.7-123.5 ncat per mg protein) and ligninase (22-106 units
      per mg protein). The addition of tangerine pomace, a substrate enriched with
      aromatic compounds, to the culture medium caused an increase in the rate of bio
      synthesis of laccase and ligninase to 862 ncat per ml and 557 units per ml,
      respectively. Aromatic compounds such as p-xylidine and veratric aldehyde
      increased the laccase activity of C. unicolor IBB 62 from 7.9 to 23.6 and 18.3
      ncat per mg protein, respectively. Veratryl alcohol caused a sevenfold increase
      in the activity of Mn-dependent peroxidase in the culture medium.

PMID- 12068575
TI  - [Extracellular chitinase production by wild-type B-10 and mutant M-1 strains of
      Serratia marcescens].
AB  - Molecular weights of extracellular chitinases from wild-type B-10 (62, 54, 43,
      38, and 21 kDa) and mutant M-1 strains of Serratia marcescens (62, 52, 43, 38,
      and 21 kDa) were estimated by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. In the absence of chitin inductors, chitinolytic enzymes were
      not found in the culture liquid of B-10, while M-10 cells produced the chitinase
      complex (to 470 pU/cell). Crystalline chitin insignificantly stimulated the
      synthesis of chitinases with molecular weights of 62, 54, and 21 kDa by B-10 (up
      to 20 pU/cell), but caused overproduction of all chitinases by the mutant strain
      (up to 2600 pU/cell). Colloidal chitin induced the production of chitinases by
      cells of both strains. Two peaks of chitinolytic activity were observed during
      cultivation of strains B-10 (350 and 450 pU/cell) and M-1 (2200 and 2400
      pU/cell). The first peak of cell productivity was associated with biosynthesis of
      the chitinase complex. The second peak was related to the production of enzymes
      with molecular weights of 54, 43, 38, and 21 kDa (B-10) or 43, 38, and 21 kDa (M
      1).

PMID- 12068577
TI  - [Secondary antimicrobial metabolites produced by thermophilic Bacillus spp.
      strains VK2 and VK21].
AB  - A collection of thermophilic strains of the genus Bacillus was made. The strains
      were screened for antimicrobial activity. Strains VK2 and VK21 isolated from
      thermal springs of the Kamchatka Peninsula, and antagonistic to several gram
      positive bacterial species were chosen for further investigation of antibiotics
      produced by them. Restriction analysis of DNA coding for 16S rRNA showed that
      both strains can be assigned to Bacillus licheniformis. It was shown that the
      lytic activity of strains VK2 and VK21 was not related to the synthesis of
      hydrolytic enzymes. The maximum level of antimicrobial activity in the growth
      medium was found to correspond to the beginning of the stationary growth phase.
      Addition of manganese sulfate induced sporulation and altered significantly the
      time course of antibiotic production in both strains. Active metabolites were
      extracted with n-butanol. They survived boiling for 30 min and were resistant to
      trypsin and chymotrypsin but were partly hydrolyzed by pronase. They were stable
      at a pH range of 2.0-9.0.

PMID- 12068578
TI  - [Riboflavin overproduction in 4-aminopyrazole[3,4-d]pyrimidine-treated yeast
      Pichia guilliermondii].
AB  - More than 90 mutants resistant to the adenine analogue 4-aminopyrazole[3,4
      d]pyrimidine (4-APP), were isolated from a wild-type strain of yeast Pichia
      guilliermondii. Some of Appr mutants accumulated noticeable amounts of products
      absorbing at 260 nm in the culture medium, probably nucleotides and their
      derivatives. In comparison to the parent strain, the mutant Appr-27 synthesized
      greater amounts of xanthine and uracil suggesting the presence of defects in the
      regulation of de novo biosynthesis of purines and pyrimidines. The regulatory
      mutations rib80 and rib81 are known to cause riboflavin (RF) overproduction and
      derepression of RF-producing enzyme synthesis in P. guilliermondii. The mutant
      Appr-27 was crossed to the rib81 strain. The yield of RF biosynthesis in some
      meiotic segregants was significantly higher than that in segregants from the
      diploid rib81/RIB81. Apparently, rib81 and appr mutations were combined in single
      genome on the favorable genetic background. An increase in RF production was also
      found in strains with appr mutations induced directly in the genome of the RF
      oversynthesizing strain rib80 rib81. These results indicate that introduction of
      appr mutations into genome of P. guilliermondii can intensify their RF
      overproduction.

PMID- 12068576
TI  - [Optimization of the medium and cultivation conditions of Penicillium roquefortii
      f39 producing the diketopiperazine alkaloid roquefortine].
AB  - We optimized the medium for cultivation of Penicillium roquefortii f39, a
      producer of roquefortine. In this medium, the roquefortine yield increased 1.5-2
      fold. The increase in roquefortine content was associated with high biomass
      yield, but not with an increase in biosynthetic activity of the mycelium. Direct
      correlation was found between extracellular roquefortine concentration and amount
      of the inoculum. The introduction of sucrose into the growth medium allowed us to
      increase the concentration of roquefortine during fermentation to 90 mg/l.

PMID- 12068579
TI  - [Selection of Penicillium funiculosum strains with high glucose oxidase
      activity].
AB  - Metabolic inhibitors, riboflavin, and end products of glucose oxidation were
      shown to hold much promise for the selection of Penicillium funiculosum mutant
      strains with a high glucose oxidase activity. The incidence of positive mutations
      was highest in clones resistant to sodium azide, riboflavin, and beta-D-glucono
      delta-lactone. Enzyme activity in Penicillium funiculosum mutants was studied
      under conditions of submerged cultivation. The intensity of glucose oxidase
      synthesis in seven cultures was 24-56% higher than that in the parent strain of
      Penicillium funiculosum NMM95.132.

PMID- 12068580
TI  - [Effects of p-nitrophenol and organophosphorous nitroaromatic insecticides on the
      respiratory activity of free and immobilized cells of strains S-11 and BA-11 of
      Pseudomonas putida].
AB  - The possibility of using the respiratory activity (RA) of microbial cells (of
      strains S-11 and BA-11 of Pseudomonas putida) as an instrument for quantitative
      determination of organophosphorous nitroaromatic insecticides, metaphors and
      sumithion, and their hydrolysis product, p-nitrophenol (PNP), has been explored.
      The dependences of RA on the concentrations of the three compounds were linear
      within the range 0.5-2.5 microM. The cells of the strain BA-11 exhibited maximum
      selectivity in the determination of the compounds. The RA of microbial cells
      differing in the modes of immobilization (adsorption to carrier surfaces vs.
      incorporation into gels) have been compared. Prospects of development of the
      microbial cell-based sensor system for determining metaphors, sumithion, and PNP
      in aqueous media are discussed.

PMID- 12068581
TI  - [The nature of melanin pigments from some micro- and macromycetes].
AB  - New inhibitors of melanin formation by micromycetes Aspergillus carbonarius,
      Alternaria alternata, and Paecilomyces variotii and basidiomycetes Inonotus
      obliquus and Phellinus robustus were found. Precursors of melanin pigments were
      isolated and identified. p-Hydroxybenzoic acid was identified among the products
      of alkaline degradation of melanin formed by micromycetes, whereas in the case of
      macromycetes this was protocatechuic acid. Therefore, melanins of the former were
      found to belong to the dihydronaphthalene group, whereas those of the latter
      belong to catechols.

PMID- 12068582
TI  - [Changes in the antigenic properties of Azospirillum brasilense
      lipopolysaccharide on addition of tris(hydroxymethyl)-aminomethane into the
      culture medium].
AB  - Addition of tris(hydroxymethyl)-aminomethane (Tris) into the culture medium of
      Azospirillum brasilense sp245 changes the antigenic properties of the
      lipopolysaccharide (LPS) isolated from the external membrane of the bacteria. LPS
      preparations from the bacteria grown in the presence of Tris have been analyzed
      by immunodiffusion, using monospecific antibodies. The disappearance of the
      precipitation band corresponding to one of the two O-specific polysaccharides of
      the LPS (O-PS1) and changes in the electrophoretic profile have been revealed.
      However, only minor differences in absorption spectra of products of O-PS1
      reaction with phenol/sulfuric acid have been demonstrated between the bacteria
      grown under standard conditions and in the presence of Tris.

PMID- 12068583
TI  - [Effect of iron compounds on the treatment of fat-containing wastewaters].
AB  - Effects of iron compounds on methanogenic fermentation the water polluted with
      fatty acids were studied. A natural readily available source of iron applicable
      to biological treatment of liquid wastes was searched for. A positive effect of
      iron on the methanogenic fermentation of fats and their degradation products-
      long-chain fatty acids--in aqueous media was demonstrated. It is recommended to
      add iron-containing clay, as an inexpensive and easily available iron source, in
      amounts providing the binding of the long-chain fatty acids present in
      wastewaters.

PMID- 12068584
TI  - [Immobilizing of Bacillus mucilaginosus--a producer of exopolysaccharides, on
      chitin].
AB  - The bacteria Bacillus mucilaginosus were immobilized on chitin sorbents.
      Exopolysaccharides produced by B. mucilaginosus were capable of sorbing
      efficiently copper ions. A composite biosorbent involving the chitin derivative
      Khizitel with immobilized B. mucilaginosus cells at the stage of active
      exopolysaccharide synthesis was developed.

PMID- 12068585
TI  - [Production and analytical properties of antibodies with high specificity to
      zearalenone].
AB  - The time course of production, specificity, and analytical potential of anti
      zearalenone polyclonal rabbit antibody synthesized by formaldehyde condensation
      and conjugated to bovine serum albumin were investigated. The relative cross
      reactivities with natural analogues were: zearalenone, 100%; alpha-zearalenol,
      0.15%; and beta-zearalenol, < 0.02%. With synthetic analogues: zearalanone, 31.7%
      and alpha-zearalanol, 0.12%. An enzyme immunoassay for zearalenone with a
      sensitivity of 0.1 ng/ml was developed on the basis of these antibodies and solid
      phase conjugates homologous to the immunogen in the method of synthesis.

PMID- 12068586
TI  - [Changes in the antioxidant properties of substituted phenol polydisulfides
      during interaction with human serum albumin].
AB  - Gallic acid polydisulfide and poly(2-aminodisulfide-4-nitrophenol) in aqueous
      solutions were shown to form polycomplexes with human serum albumin. This process
      was accompanied by considerable changes in the spectrum of protein circular
      dichroism recorded in distilled water in the far UV range at 20 degrees C.
      Complex formation between human serum albumin and polydisulfides was followed by
      a marked decrease in the content of alpha-helices and increase in the count of
      antiparallel beta-structures in the protein. Stable complexes containing 1.5,
      2.8, and 7.7 poly(2-aminodisulfide-4-nitrophenol) molecules per human serum
      albumin molecule were formed in bicarbonate buffer (pH 9.0). In these complexes,
      the secondary protein structure underwent changes similar to those in
      polycomplexes of human serum albumin and polydisulfides. Gallic acid
      polydisulfide and poly(2-aminodisulfide-4-nitrophenol) inhibited the catalase
      induced degradation of 50 mM H2O2. Complexes of human serum albumin and poly(2
      aminodisulfide-4-nitrophenol) increased the catalytic activity and operational
      stability of catalase 1.5 and 4-7-fold, respectively. This was characterized by
      the effective reaction rate constant (kin, s-1). Our results indicate that
      complexes of human serum albumin and substituted phenol polydisulfides act as
      potent protectors and activators of catalase during enzymatic degradation of H2O2
      at high concentrations.

PMID- 12068587
TI  - [The use of elicitors for defense of agricultural plants demands caution].
AB  - Hazards of the use of biogenic elicitors for inducing protective mechanisms in
      plants without considering the possible negative effects of the elicitors are
      considered.

PMID- 12068588
TI  - [Effect of various phytoimmunocorrectors on fruit and soft fruit cultures].
AB  - Catalase activity and induction of delayed chlorophyll fluorescence were shown to
      be the markers of plant native state. The dependence of reaction of the plant to
      exogenous elicitors, stimulators or inhibitors of defense system, on the age,
      cultivar and/or species was found. Prolonged effect of the treatment with
      phytoimmunocorrectors was observed. The necessity of careful choice of elicitors
      depending on the plant state was shown.

PMID- 12068590
TI  - [Turbidimetric method for quantitative determination of triton X-100 with
      silicotungstic acid].
AB  - The Formation of Triton X-100-silicotungstic acid complex was studied.
      Quantitative turbidimetric determination of the detergent based on this process
      was suggested. This method allows to determining the complex formation at any
      wavelength in the range from 350 (epsilon 350 = 15,600 cm-1 M-1) to 600 nm
      (epsilon 600 = = 9090 cm-1 M-1). The calibration curve for Triton X-100 recorded
      at 350 nm is linear in the concentration range of 0 to 30 micrograms/ml. A
      sigmoid calibration curve was observed at longer wavelengths. A linear fragment
      of the calibration curve recorded at 600 nm was found at a concentration of
      Triton X-100 of about 5 micrograms/ml. The complex nature of calibration curves
      can be explained by heterogeneity of the complex dispersion.

PMID- 12068589
TI  - [Evaluation of correlation between the content of alkaloids and chemical elements
      in Washington lupin (Lupinus polyphyllus Lindl.) besed on statistical analysis
      and mathematical simulation].
AB  - A considerable number of linear and nonlinear correlations between concentrations
      of quinolizidine alkaloids and concentrations of K, Ca, Mg, Ba, Zn, Cu, Ni, and V
      were found in lupin seeds and leaves by using methods of correlation and
      regression analysis. Mathematical models of regulation of alkaloid metabolism by
      these chemical elements were constructed. The models of regulation were
      considered separately for individual plant organs.

PMID- 12068591
TI  - [Determination of maximum permissible concentrations of industrial toxicants
      using the integral biochemical index].
AB  - Effects of patented mixtures of substances, used as drilling fluids in petroleum
      industry, on the activity of enzymes (cathepsin D, EC 3.4.23.5; catalase, EC
      1.11.1.6; and DNase, EC 3.1.4.6) and the content of analytes (malondialdehyde,
      fatty acids, free and collagen-associated hydroxyproline, bile acids, and total
      protein) in liver, gills, muscles, gonads, and bile have been studied under
      aquarium conditions in mature river flounder and one-year-old salmon for the
      purpose of determining maximum permissible concentrations. Measuring 25-30
      independent biochemical parameters per organ is sufficient for establishing a
      direct relationship between the concentration of an industrial toxicant and the
      integral biochemical index, a new characteristic defined as the ratio of the
      number of biochemical parameters significantly deviating from control values to
      the total number of the parameters measured.

PMID- 12068592
TI  - [Water structure formation by weak magnetic fields and xenon. Electron
      microscopic analysis].
AB  - Exposure of deionized water of high purity grade to weak magnetic fields
      (collinear fields: the constant component 42 +/- 0.1 microT; the alternating
      component: amplitude 60 +/- 2 nT, frequency 3.7 Hz) for 12 h affects the
      structure formation in a water-xenon system. This is evidenced by the formation
      of xenon clathrate crystals a few submicrons and microns in size whereas in
      initial water solution these crystals were absent. The changes in water
      properties persist for at least two days after the treatment with magnetic
      fields. The addition into water of calcium ions at a concentration close to
      physiological completely eliminates the effect of the formation of submicron and
      micron crystals of xenon gas hydrates.

PMID- 12068593
TI  - [Thermodynamic properties of bulk knitted structures].
AB  - The mechanism of interaction of an external magnetic field with liquid was
      proposed. The statistical integral and configurational contributions for a free
      energy, entropy and specific heat for the soliton model of bulk knitted
      structures in a magnetic field were calculated. It was shown that the
      concentration of solitons depends on the effect of external fields. In the
      specific case of bulk knitted structures (liquid water without magnetic field),
      the theoretical data are consistent with experimental. The memory effects in
      systems with hydrogen bonds in magnetic field was explained in the framework of
      the continuum soliton concept.

PMID- 12068594
TI  - [Molecular dynamics of bending fluctuations in the protein secondary structures].
AB  - A comparative study of the dynamics of protein secondary structure elements by
      the example of alpha-helices of myoglobin, barnase, polylysine, and polyglycine
      and beta-layers of barnase and GFP was carried out by the methods of molecular
      dynamics. The effective Young's moduli of both free secondary structure elements
      and those built in the protein globule were determined. A heterogeneity of the
      elastic properties of the secondary structure elements was found. The melting of
      myoglobin alpha-helix in a virtual viscous medium was studied.

PMID- 12068595
TI  - [Energetics of hydration of nucleic acids with various nucleotide composition].
AB  - The energetics of hydration of natural DNA of different AT/GC content and model
      double-helical polyribonucleotides was studied. The results obtained by a new
      approach, which is based on calorimetric measurements of hydration-dehydration
      energy of nucleic acid-water systems at different relative humidities are
      presented. A correlation between the dehydration energy and the nucleotide
      composition of native DNA was found. The energetic characteristics of systems
      containing deoxynucleoside monophosphates and water clusters of different
      dimensions were obtained by the Monte Carlo method. The results of computer
      simulation correlate with the experimental calorimetric data.

PMID- 12068596
TI  - [Conformation of a DNA molecule in water-salt solutions depends on the salt anion
      type].
AB  - The methods of viscosimetry and flow birefringence were used to study the effect
      of anions F-, Cl-, Br-, J-, NO3-, ClO4-, SCN-, CH3COO- on the dimensions and
      thermodynamic rigidity of the DNA molecule in solutions in a wide range of ionic
      strengths and at different temperatures. It was shown that the persistent lengtH
      of DNA is independent of the anion type at all values of ionic strength, and the
      changes in its dimensions, which are determined from the changes in intrinsic
      viscosity, are due to the influence of anions and their hydration on long-range
      interactions in the macromolecule. Possible reasons for this phenomena and the
      role of structural changes in water upon hydration of anions are discussed.

PMID- 12068597
TI  - [Complexes of DNA with trivalent metal ions in presence of manganese ions].
AB  - The interaction of DNA with Fe3+, Al3+, Co(NH3)6(3+) in a solution containing
      MnCl2 was studied. It was shown that there exists a competition for the binding
      sites between Mn2+ and Al3+, while the binding of Mn2+ to DNA does not depend on
      the presence of Fe3+ and Co(NH3)6(3+) in solution. We proposed that Fe3+ and
      Co(NH3)6(3+) ions prefer to bind to phosphates, and Al3+ ions are capable to bind
      to the nitrogen bases of DNA.

PMID- 12068598
TI  - [Interactions of DNA with ampholytes based on actinocin].
AB  - The interaction of DNA with actinocin monoamides containing a substitute with the
      cationoide center in one of the amide groups were studied by spectrophotometry,
      induced circular dichroism, viscometry and flow birefringence methods. At pH
      values of solution exceeding their isoelectric point, these substances, which are
      in nature ampholytes, occur as zwitterions. At lover pH values they occur in the
      cationoid form. The constants of binding of these compounds to DNA were
      determined, and changes in DNA macromolecular structure caused by complexation
      were revealed. Models for the binding of these compounds to DNA were advanced. It
      was shown that compounds in the zwitterion form do not intercalate into the DNA
      double helix. The mode of binding of compounds to DNA in the cationoid form
      depends on the position of the cationoid center within the chromophore actinocin.
      Circular dichroism spectra of actinocyn-based ampholytes that bind to DNA in a
      different manner were obtained.

PMID- 12068599
TI  - [Effect of a substituent origin in actinocin amides on their binding to DNA].
AB  - The results of studies on the structure of complexes of DNA with compounds based
      on the actinocin chromophore, a center of binding of the antitumor antibiotic
      actinomycin D to DNA, were analyzed. In positions 1 and 9 of the chromophore of
      these compounds, pentapeptide lact ones of actinomycin D are replaced by groups
      of various origin. By using spectral, optical, and hydrodynamic methods a model
      of binding to DNA for each compound was constructed, and some regularities of
      complex formation depending on the structure of actinocin substituents and the
      amount of ligands in the complex were revealed.

PMID- 12068600
TI  - [Interactions of a DNA molecule with coordination compounds of platinum and
      cobalt in solutions].
AB  - The interaction of DNA with coordination compounds of divalent platinum and
      trivalent cobalt was studied. Complexes containing simultaneously different
      coordination compounds were prepared by various procedures. It was shown that the
      binding of trans-diaminodichloroplatinum (DDP) to DNA prevents its further
      complexing with cis-DDP, while in the presence of cis-DDP the possibility for
      trans-DDP to bind to DNA in solution remains. The study of similar DNA complexes
      with trans-DDP and cobalt hexamine indicated the competition for the binding
      sites of these compounds to the DNA molecule.

PMID- 12068601
TI  - [A comparison of effects of agents stabilizing or destroying the water structure
      on conformational changes of a DNA molecule in solutions exposed to gamma
      irradiation].
AB  - It was shown that gamma-irradiation of water-ethanol and water-n-propanol
      solutions of DNA with doses of 10-30 Gy leads to a fall of the specific volume of
      the macromolecule upon the cooperative transition at a critical concentration of
      alcohol in solution at which the destroying of water structure by a
      nonelectrolyte occurs.

PMID- 12068602
TI  - [Thermodynamic analysis of interaction of mitoxantrone with deoxytetranucleotide
      5'-d(TpGpCpA) in the water solution based on 1H-NMR spectrophotometry].
AB  - The complex formation of the antibiotic mitoxantrone (novantrone) with the
      deoxytetranucleotide 5'-d(TpGpCpA) in an aqueous salt solution was studied by one
      and two-dimensional (2D-TOSCY and 2D-NOESY) 1H NMR spectroscopy (500 MHz).
      Concentration and temperature dependence of proton chemical shifts of molecules
      were measured. On the basis of these data, the equilibrium constants of the
      reaction, the relative content of various complexes as a function of
      concentration and temperature, the limiting values of chemical shifts of
      novantrone in complexes, and the thermodynamic parameters delta H and delta S of
      complex formation of molecules were calculated. It was concluded that the
      attachment sites for novantrone are pyrimidine-purine nucleotide sequences, sites
      d(TG) and d(CA) of the tetranucleotide duplex. The analysis of the thermodynamic
      parameters of the complex formation suggests that intermolecular hydrogen bonds
      and electrostatic interactions of the aminoalkyl chains of novantrone with the
      duplex d(TpGpCpA)2 play an important role in the stabilization of complexes 1:2
      and 2:2. The results were compared with those obtained earlier for typical
      intercalators of ethidium bromide and daunomycin under identical experimental
      conditions.

PMID- 12068603
TI  - [The rank of data matrices in a spectrophotometric study of a ligand-biopolymer
      complex formation].
AB  - The dependences of concentrations of ligand-linear polymer complex species vs.
      the concentration of free ligand were calculated. The analysis of the data
      suggests that the variance of the property studied considerably depends on the
      parameters of ligand-polymer complex formation (cooperativity and the average
      number of monomers occupied by the ligand). The rank of the matrix of
      concentration fractions of species was estimated using the singular value
      decomposition by the method of principal component analysis. As the cooperativity
      increases, the rank matrix decreases from 4 to 2. An increase in the average
      number of monomers occupied by the ligand at high cooperativity leads to an
      increase in the matrix rank from 2 to 3.

PMID- 12068604
TI  - [Effects of relaxation processes on the temperature dependence of oxidation rate
      of photooxidized bacteriochlorophyll on the primary quinone in reaction centers
      of Rhodobacter sphaeroides].
AB  - The temperature dependence of the time of dark recombination of charges between
      photooxidized bacteriochlorophyll and reduced primary quinone acceptor (tau e) in
      Rhodobacter sphaeroides photosynthetic reaction centers was studied in the
      temperature range 140-320 K. It was found that the function tau e = tau e(T) is
      nonmonotonous: in the temperature range from 140 to 290 K, tau e is increased
      from 40 to 100 ms; however, under further heating to 320 K, tau e decreased to 80
      ms. The replacement of H2O by D2O in these preparations caused an acceleration of
      the recombination process in the range of physiological temperatures, but the
      nonmonotonous character of the function tau e(T) remained. The theoretical
      interpretation of the results was made in the framework of the theory of electron
      phonon interactions with allowance for the relaxation processes.

PMID- 12068605
TI  - [A model of electron transport in chloroplasts taking into account the Mitchell Q
      cycle. Calculation of J(e) and J(H) fluxes in steady state].
AB  - On the basis of the earlier proposed model of electron transport, which takes
      into account the Mitchell Q-cycle, stationary values for the fluxes of electrons
      Je along the electron transport chain and of protons JH across the thylakoid
      membrane were obtained, which are calculated now as the functions of
      photoexcitation of reaction centers and the medium acidity inside and outside of
      the thylakoid, pHin and pHout. In the framework of the model, the stoichiometric
      ratio JH/Je is determined virtually only by the time of reduction of
      plastoquinone (tau B) on the B site of photosystem II and restoration of
      plastoquinone (tau C) on the C site to the b/f complex.

PMID- 12068606
TI  - [Participation of inorganic phosphates as electron donors in the primary
      reactions of photosynthesis in Rhodobacter sphaeroides].
AB  - The formation of ATP during photophosphorylation in chromatophores from purple
      nonsulfur bacterium Rhodobacter sphaeroides in the presence of phenazine
      methosulfate and without exogenous electron carriers under constant illumination
      and by the action of single light flashes was studied. It was shown that the
      photoinduced transport of electrons to the exogenous electron acceptor depends on
      phosphate. It was assumed that phosphate ions are electron donors in the reaction
      center P870; by the action of light, P870 converts the phosphate ion HPO4(2-)
      into anion radical HPO4-.. In the difference EPR spectra "light minus darkness"
      at 77 K, an asymmetrical doublet signal with a weak low-field line was observed.
      The signal had a g-tensor of about 2.014 and a hyperfine coupling constant of
      about 2.5 mT and belongs probably to the phosphate anion radical.

PMID- 12068608
TI  - [Interaction of local anesthetics with model ion channels].
AB  - A theoretical study of intermolecular interactions between local anesthetics of
      the acetanilide series and model ionic channels was performed. A dimer of
      gramicidine A and melittin were used as models of ionic channels. The geometry of
      molecules was determined by the method of molecular mechanics. Statistically
      significant correlation equations were derived, which relate the indices of local
      anesthetizing activity to the characteristics of intermolecular interactions in
      the anesthetic-peptide system. A comparative analysis of intermolecular
      interactions in anesthetic-gramicidine A and anesthetic-melittin systems was
      carried out.

PMID- 12068607
TI  - [Effect of diamide on protein oxidation and physico-chemical properties of lipids
      in erythrocyte membranes].
AB  - The effect of diamide on the physicochemical state of proteins and lipids of
      human erythrocyte membrane was studied. It was found that diamide at a
      concentration of 1 mM decreases the content of the SH-groups of membrane proteins
      by approximately 50%, resulting in enhanced vesiculation of erythrocytes upon
      metabolic exhaustion of cells. It was shown using fluorescein isothiocyanate
      labeled concanavalin A and 4,4'-diisothiocyano-2,2'-stilbene disulfonate that
      diamide changes the structural state of the main integral protein of erythrocyte
      membranes, the band 3 protein. Changes in the microviscosity of the membrane
      lipid bilayer depending on diamide concentration were determined from the changes
      in the fluorescence parameters of the lipophilic probes (pyrene and 1,6-diphenyl
      3,5-hexatriene). The level of lipid peroxidation products in membranes remained
      unchanged. It follows from these data that the SH-oxidizing agent diamide does
      not directly interact with the lipid bilayer of membrane and produces changes in
      the physicochemical state of lipids presumably by disrupting protein-lipid
      interactions that take place upon oxidation of the SH-groups and cross-linking of
      membrane proteins.

PMID- 12068609
TI  - [Determination with a microelectrode of membrane potential of giant human
      erythrocytes obtained by La(3+)-induced fusion].
AB  - The effect of La3+ on the fusion of erythrocytes of blood stored for a week at +4
      degrees C was studied. It was shown that the fusion of erythrocytes begins after
      one day of storage of blood. The most intensive fusion of erythrocytes was
      observed on day 4 of blood storage. As a result, giant cells with a size of 100
      microns and more arise. The electrical potential of giant cells was measured
      using a microelectrode and was -6.6 +/- 1.5 mV.

PMID- 12068610
TI  - [Participation of extracellular polysaccharides in detoxication of cadmium ions
      by cyanobacteria Nostoc muscorum].
AB  - Using the methods of absorption and fluorescence spectroscopy, histochemistry and
      micrography, the influence of cadmium in different concentrations on the
      exudation of exopolysaccharides by Nostoc muscorum was studied to elucidate the
      possibility of distance detoxication of cadmium ions by the cyanobacterium with
      the participation of its exometabolites. The toxic action of Cd was controlled by
      changes in biomass, trichomes morphology, and the photosynthetic apparatus of the
      cyanobacterium. The content of exopolysaccharides in the extracellular medium was
      0.7 +/- 0.01 gram glucose units per gram dry biomass at the culture density of 2
      gram dry biomass per liter. In the initial phase of growth, the exopolysaccharide
      content decreased to 0.4 +/- 0.1 gram glucose units per gram dry biomass, while
      upon incubation with cadmium ions it increased several times during a week, after
      a short adaptation period. The kinetics of exopolysaccharide accumulation and
      their concentration depended on cadmium content in the medium. After the
      incubation of N. muscorum with Cd2+, the exometabolites and the mucous coat
      colored with ditizone, which was indicative of cadmium accumulation. The
      decomposition of the absorption spectra of the hydrolyzed extracellular
      metabolites showed that in the presence of cadmium ions, the dominant
      monosaccharide became glucosamine, which readily binds to Cd2+. It was concluded
      that the system of N. muscorum protection against cadmium includes the binding of
      the metal by cell structures, primarily, by the mucilaginous sheath and the
      distance detoxication by exopolysaccharides in the cultural medium. Cadmium
      induces the activation of the mucilaginous sheath protective function by changing
      its composition and the rate of renewal. To provide the distance protection of N.
      muscorum, the rate of polysaccharide release of the altered primary structure
      increased.

PMID- 12068611
TI  - [Permeabilization of tumor cells induced by pulsed electric fields in vitro].
AB  - The permeabilization of tumor cells in vitro under the action of pulsed electric
      fields with a duration of 6 mks in the range of amplitudes 1-7 kV/cm was studied.
      In the mode of excitation in the ambience of localized plasma discharge in a
      chamber of special design, an enhanced damage to cells in suspension was
      observed. It is assumed that the enhancement is due to the synchronous action of
      the electric field and acoustic shock wave pulses. In the mode without the plasma
      breakdown of ambience, when the pulse duration of electric field of intensity of
      1-2 kV/cm was increased to 60 mks, the efficiency of permeabilization increases
      nearly by one order. The experimental results are compared with the known
      theoretical models of cell membrane electroporation.

PMID- 12068612
TI  - [Effect of combination of high-voltage pulses and other physical factors on the
      intensity of reproduction of Anabaena flos aquae].
AB  - It was shown that the influence of high-voltage pulses (intensity of electric
      field 40-120 kV/cm) on cyanobacteria Anabaena flos aquae can be different and
      depends on the mode of treatment. It was found that in the range of pulse
      durations less than 1 microsecond with a pulse repetition rate of up to 500 Hz,
      and final temperature in the working chamber (60 +/- 1) degree C, a gradual full
      and irreversible inactivation of cyanobacteria independent of the pulse shape
      takes place. At the same time, a rapid (but slower than by the action of high
      voltage pulses) heating without treatment with high-voltage impulses at the same
      final temperature leads to an inactivation of 80% of initial cyanobacteria
      followed by growth of bacteria up to 700% and more.

PMID- 12068613
TI  - [Fluorescent analysis of cryopreserved totipotent cells of amphibian embryos].
AB  - The cryotolerance of totipotent cells from dissociated embryos of amphibian
      (grass frog Rana temporaria and grey toad Bufo bufo) was studied. Cell integrity
      and preservation of the cell barrier function were evaluated by fluorescent
      analysis. It was shown that the best cryopreservation of the cells was achieved
      by using the cryoprotective agent 10% dimethyl sulfoxide and 10% saccharose.
      These cells were successfully used for the homotransplantation of nuclei into
      enucleated eggs. The development of reconstructed eggs to the blastula stage was
      noted.

PMID- 12068614
TI  - [Spatial distribution of synthetic activity in zone-forming colonies of soil
      Streptomycetes].
AB  - The space distribution of synthetic activity in the substrate mycelium gyphs-
      structure growth units of a quasiorganism of the radiant fungus, was studied by
      the method of microspectral analysis. A detailed map of the distribution on the
      alpha-parameter (which reflects the level of synthetic activity) from the cross
      section of a living streptomyces colony was constructed. The data obtained
      support with a high reliability the earlier supposition that the maximum of
      synthetic activity is in the growth zone and the minimum synthetic activity is in
      the globular regions of formation of air mycelium protogyphs. The use of
      objectivity characteristics made it possible to thoroughly study the development
      of globular structures, the precursors and sources of formation of air mycelium
      concentric zones on colony surface.

PMID- 12068615
TI  - [Evaluation of viscoelastic property inhomogeneities in soft tissues exposed to
      low frequency perturbations].
AB  - This work presents the methods of recognition of inhomogeneities of tissue shear
      viscoelastic properties using partial data on the internal displacements in an
      object exposed to low-frequency perturbation. An approach to detect tissue
      inhomogeneities using the single displacement component is presented.

PMID- 12068616
TI  - [Associative neurons as correlators].
AB  - The paper continues the series of studies devoted to the hypothesis that the
      brain functioning occurs with the participation of correlation methods. The
      processing of signals by these methods is sufficiently versatile to provide the
      solution of diversified problems, which has been shown in studies of the
      mechanisms of animal echo location (a correlation model of echo location) and
      recognition of objects at any modality of sensor signals. It was shown that the
      mode of processing performed by neurons correlometers corresponds to the
      character of signals coming from the habitat of animals. Problems related to both
      the peculiarities of a reference signal formed by synaptic inputs of an
      associative neuron and the process of calculating the correlation function by
      this neuron were resolved. Two mathematically equivalent ways of physical
      execution of calculating the correlation function, by a correlometer and a
      passive correlated filter, were compared. The advantages of the brain that
      performs the correlation processing of signals by using the aggregates of neurons
      functioning as systems of correlometers rather than passive filters are analyzed.

PMID- 12068617
TI  - [Dependence of effects of weak combined low-frequency variable and constant
      magnetic fields on the intensity of asexual reproduction of planarians Dugesia
      tigrina on the magnitude of the variable field].
AB  - It was shown that the stimulating effect of weak combined magnetic fields
      (constant component 42 microT, frequency of the variable component 3.7 Hz) on the
      division of planarians depends on the amplitude of the variable component of the
      field. The effect is particularly pronounced at 40 (the main maximum), 120, 160,
      and 640 nT. Narrow ranges of effective amplitudes alternate in some cases with
      equally narrow ranges in which the system does not respond to he treatment. In
      the range of super weak amplitudes of the variable field (0.1 and 1 nT), the
      stimulating effect is poorly pronounced. The data obtained indicate the presence
      of narrow amplitude windows in the response of the biological systems to weak and
      super weak magnetic fields. In a special series of experiments, it was shown that
      the effect of fields on planarians is partially mediated via aqueous medium
      preliminarily treated with weak magnetic fields. It is noteworthy that in
      experiments with water treated with weak magnetic fields, there were no
      pronounced maxima and minima in the magnitude of the effect in the range of
      amplitude of the variable magnetic field from 40 to 320 nT.

PMID- 12068618
TI  - [Urine surface tension in patients with urolithiasis treated with pharmalite].
AB  - It was shown that pharmalite is an effective drug in the therapy of urolithiasis.
      The efficiency of pharmalite was determined from the surface tension of urine.

PMID- 12068619
TI  - [A negative result of the experimental verification of distant effect of
      bactericidal agents on the growing bacterial culture].
AB  - The incontact action of penicillin and ethidium bromide on dividing bacterial
      culture Escherichia coli through ampoule glass or by means of antennae was
      studied. No statistically significant differences in cell division between
      samples exposed to distant action and control were found, though contact action
      of both substances reduced division considerably.

PMID- 12068620
TI  - [A baculovirus expression system for insect cells].
AB  - The review considers the biology of baculoviruses, construction of transfer
      vectors for the baculovirus expression system, selection of recombinant
      baculoviruses, approaches to expression of multimeric proteins, and the
      potentialities and prospects of the system.

PMID- 12068621
TI  - [Sensitivity of the folding pathway to the details of amino acid sequence].
AB  - Experimental data on the structure of transition state demonstrate that the
      proteins with the same topology as a rule have similar folding nuclei (the
      structured formed part of the transition state). In this review we discuss the
      experimental works which show that the position of folding nuclei is different
      among proteins with the same topology. These facts underline that the folding
      pathway is sensitive to the details of amino-acid sequence.

PMID- 12068622
TI  - [Nucleosome structural dynamics and super spiral linking number paradox].
AB  - The minireview presents recent results obtained in the experiments with DNA
      minicircles containing reconstituted nucleosomes. This system allows one to
      register and to characterize conformational dynamics of nucleosomes and of
      subnucleosomal particles containing histone tetramer (H3-H4)2. In particular, it
      has revealed an important role of the histone N-terminal tails in this dynamics.
      Solution of the linking number paradox and relevance of the results obtained to
      chromatin structural dynamics are discussed.

PMID- 12068623
TI  - [Synaptonemal complex proteins: specific proteins of meiotic chromosomes].
AB  - The review considers proteins of the synaptonemal complex (SC), a specific
      structure formed between homologous chromosomes in maturing germline cells during
      meiotic prophase I. The structure and functions are described for proteins that
      form ultrastructural SC elements in mammals, in yeast, and in higher plants. The
      roles of cohesions and of the SC proteins in meiotic sister-chromatid cohesion
      are considered. Though still scarce, data are summarized on the SC self-assembly
      and dissociation and on the molecular composition of SC-associated recombination
      nodules, which provide a compartment for meiotic recombination enzymes. The
      accumulating data on the SC molecular components and on their structure,
      properties, and interactions improve the understanding of the SC function.

PMID- 12068625
TI  - [The effect of the nucleotide context on induction of mutations in hypervariable
      segment 1 of the human mitochondrial DNA].
AB  - The distribution of unstable nucleotide positions with a higher frequency of
      homoplastic mutations was analyzed in hypervariable segment 1 (HVS1) of the major
      noncoding region of human mtDNA. Three motifs (GTAC, ACCC, CCTC) proved to be
      associated with a higher rate of point substitutions at unstable positions. The
      motifs were often arranged in direct, including tandem, repeats. Motifs CCTC and
      ACCC were found in extended poly(C) tracts, which form direct repeats associated
      with deletions and tandem duplications. The results suggested that the
      inconstancy of the human mitochondrial genome is to a great extent determined by
      context-dependent mutations.

PMID- 12068624
TI  - [The mitochondrial genome of higher plants: gene expression regulation].
AB  - The multistep regulation of mitochondrial gene expression in higher plants is
      considered. Data are summarized that concern the structure and function of the
      transcription system, posttranscriptional changes in the mRNA structure, and
      other levels of expression regulation.

PMID- 12068626
TI  - [A new approach to detect a particular DNA sequence by UV-immobilization of its
      hybridization complex with a highly specific probe resulting from ligation of a
      tandem of short oligonucleotides in solution].
AB  - A new approach was proposed for detecting amplified DNA fragments by
      hybridization with a highly selective oligonucleotide probe obtained by ligation
      of a tandem of three short oligonucleotides (pN8 + pN4 + pN8' Bio) in solution,
      with subsequent UV-immobilization of the hybridization product on a nylon
      membrane and its colorimetric detection with the streptavidin-alkaline
      phosphatase technique. Owing to the high selectivity of ligation, the 20-mer
      ligation product was detected on a membrane only when it was completely
      complementary to a template fragment. The results showed that any single
      nucleotide substitution in the tetramer-binding site can be localized and
      identified with the use of all 12 possible tetramers.

PMID- 12068627
TI  - [Comparison of the homologous SfeI and LlaBI restriction-modification systems].
AB  - A fragment containing the SfeI restriction-modification system (RMS) operon was
      cloned from a Streptococcus faecalis SE72 plasmid. Nucleotide sequence analysis
      revealed its high (99.2%) homology to the operon for Lactococcus lactis subsp.
      cremoris W56 LlaBI RMS recognizing the same site, 5'-CTRYAG-3'. A substantial
      difference was that SfeI RMS operon had an additional 198-bp fragment and a
      larger gene for the putative control protein. No homology was observed between
      operon-flanking sequences of the two closely related species, suggesting
      horizontal transfer of the operon.

PMID- 12068628
TI  - [Frequency of the 35delG mutation of the connexin 26 gene (GJB2) in patients with
      non-syndromic autosome-recessive deafness from Bashkortostan and in ethnic groups
      of the Volga-Ural region].

PMID- 12068629
TI  - [Tetranucleotide tandem repeat polymorphism of the CFTR gene intron 6B in
      populations of the Volga-Ural region].
AB  - The allele and genotype frequencies of the tetranucleotide tandem repeat (TTR) of
      CFTR intron 6B were analyzed in eight ethnic populations of the Volga-Ural
      region, including Bashkir, Tatar, Chuvash, Mari, Mordvinian, Udmurt, Komi
      Permyak, and Russian. The most common TTR allele 7 varied in frequency from 0.636
      in Chuvash to 0.805 in Mordvinians. The frequency of the second common allele 7
      ranged from 0.188 in Mordvinians to 0.333 in Chuvash. Allele 8 was found in about
      8% of Udmurts and Mari; occurred in a few Bashkirs, Tatars, Mordvinians, and Komi
      Permyaks; and was not observed in Russians. The genetic diversity coefficient was
      minimal in Mordvinians (0.496) and in Tatars (0.505), indicating their low
      heterogeneity in TTR. The observed heterozygosity was maximal in Udmurts (0.532)
      and Komi-Permyaks (0.560) and minimal in Mordvinians (0.297). In total, the
      populations proved to be heterogeneous in TTR allele frequency distribution, the
      interpopulation difference being significant in most cases.

PMID- 12068631
TI  - [Region of intermolecular complementarity in Escherichia coli 16S rRNA, mRNA, and
      tRNA molecules].
AB  - The results of computer analysis of complementarity regions in the sequences of
      E. coli 16S rRNA, mRNAs and tRNAs are reported in this article. The potential
      regions of intermolecular RNA-RNA hybridization, or clinger fragments, in 16S
      rRNA, which are complementary to the sites frequently occurring in mRNAs and
      tRNAs, were found. Major clinger fragments on 16S rRNA are universal for genes
      that belong to different functional groups. Our results show there are
      adaptations of the structural organization of the 16S rRNA molecule to messenger
      and transport RNA sequences. RNA interaction with clinger fragments may
      contribute to upregulation of translation process through increasing the local
      concentration of mRNAs and tRNAs in the vicinity of the ribosome and their proper
      positioning, as well as decrease the efficiency of translation through non
      specific mRNA-16SrRNA interactions.

PMID- 12068630
TI  - [Searching for local similarities between HIV-1 and human proteins. Application
      to vaccines].
AB  - A method for identification of fragments with a high local similarity to human
      proteins within potentially immunopathogenic regions of HIV-1 proteins was
      developed. The method is based on the use of an original matrix of antigenic
      similarity of amino acids. The regions, whose fragments are frequent in human
      proteins, and regions, exhibiting a high similarity to the proteins responsible
      for important physiological functions, were identified in HIV-1 proteins. A
      possibility of participation of such regions in immunopathogenesis of HIV
      infection due either to induction of cross-reacting effectors of immune system or
      through molecular mimicry of physiologically important human proteins, leading to
      an alteration of homeostasis of the organism, is discussed. Most of regions,
      identified in HIV-1 proteins, contain either T-cell (CD8+ CTL or CD4+ Th) or B
      cell epitopes, or both of them simultaneously. The criteria for the design of
      safe polyepitopic antiviral vaccines which enable the exclusion of epitopes,
      having the (immuno)pathogenic potential, are discussed. According to these
      criteria, polyepitopic immunogens should be free of the virus protein regions,
      whose fragments are frequent in human proteins, as well as of regions exhibiting
      a pronounced local similarity to proteins that provide for important
      physiological functions.

PMID- 12068632
TI  - [Proliferative senescence of embryo fibroblasts of Japanese senescence
      accelerated mice (SAM) is accompanied by parallel decreasing of response to
      various growth factors].
AB  - The Japanese senescence accelerated mice (SAM) are a group of the low-longevity
      mouse lines and represent a new convenient model for studying the senescence
      process. We studied the proliferation of embryo fibroblasts of SAMP1 and SAMR1
      mouse lines. It was shown that fibroblasts of the shortest longevity line SAMP1
      have a markedly decreased proliferative potential of the mean 8.7 population
      doublings, whereas fibroblasts of a relatively high-longevity line SAMR1 have an
      average proliferative potential of 12.3 doublings. The fibroblast senescence in
      both lines is accompanied by a simultaneous lowering of the cell proliferative
      response to the blood serum, epidermal, fibroblast, and platelet-derived growth
      factors. At initial stages of the cell culture growth, lines SAMP1 and SAMR1
      exhibit the same reactions to growth factors, but already beginning from the
      fifth doubling, the SAMP1 cell response is sharply decreased as compared with
      SAMR1. Lowering the proliferative reaction is accompanied by a decreased
      phosphorylation of tyrosine in the cell proteins responsible for mitogenic
      reaction. Thus, the parallel decrease of proliferative response to different
      growth factors during fibroblast senescence is most likely due the emergence of a
      regulatory block at common stages of the mitogenic signal transduction.

PMID- 12068633
TI  - [Suppression of the metastatic potential of oncogene v-src-transformed cells as a
      result of activity of the exogenous DAP kinase].
AB  - Hamster tumor cell lines obtained with the Rous sarcoma virus and characterized
      by a high metastatic activity in vitro were transfected with the gene for
      C2+/calmodulin-dependent serine-threonine death-associated protein kinase (DAPk).
      Expression of DAPk in tumor cells dramatically reduced their survival in the
      blood of syngenic animals and their ability to produce metastases, but did not
      affect their tumorigenicity or the primary tumor growth. The DAPk-induced change
      in the metastatic phenotype was not accompanied by substantial changes in
      production and phosphorylation of v-Src or focal adhesion proteins (focal
      adhesion kinase and paxilline). The resulting system of transfected cells with a
      modulated metastatic potential provide a convenient model to study the molecular
      mechanisms of tumor progression at various steps.

PMID- 12068635
TI  - [The use of the two-hybrid cloning in yeast for functional characterization of
      protein kinase MAK-V].
AB  - Identification of interaction partners opens a way to direct functional
      characterization of proteins. Several cDNAs coding for potential partners of
      protein kinase MAK-V/Hunk were isolated using two-hybrid cloning in yeast. Based
      on the partner properties, MAK-V/Hunk was assumed to play a role in tumorigenesis
      and tumor progression. With the previous results of two-hybrid cloning, MAK
      V/Hunk was shown to participate in vesicular transport.

PMID- 12068634
TI  - [Molecular portrait of human kidney carcinomas: the gene expression profiling of
      protein-tyrosine kinases and tyrosine phosphatases which controlled regulatory
      signals in the cells].
AB  - Hybridization with cDNA arrays was used to obtain expression profiles of 214
      protein-tyrosine kinase, protein-tyrosine phosphatase, dual-specific phosphatase,
      and other genes for kidney carcinomas (KC) and normal kidney tissues of 34
      patients and for seven carcinoma cell lines. Computer analysis revealed three
      clusters of genes coexpressed in KC. A proliferating-cell gene cluster included
      MET, VIM, MYC, TOP2A, PCNA, etc. A neoangiogenesis and blood-cell gene cluster
      included LCK, HCK, FGR, MMP9, CSFR1, VEGF, FLT1, and KDR. A cluster corresponding
      to normal, differentiated kidney cells included ERBB2 (HER2) for receptor protein
      tyrosine kinase, several phosphatase genes (PTPRE, PTPRB, DUSP9), and EGF. The
      results suggested that MET, DUSP9, PCNA, TOP2A, and VIM may serve as diagnostic
      and prognostic markers in KC. Tubulin and topoisomerase II were assumed to be
      promising targets for cell proliferation inhibitors in KC.

PMID- 12068636
TI  - [Interaction of RNA with phospholipid membranes].
AB  - RNAs binding with liposomes under near physiological conditions were obtained by
      molecular selection. Structural analysis showed that the RNAs could form
      complexes owing to complementary sequences located in loops. Oligomerization of
      the RNAs selected was experimentally confirmed. The results and published data
      testified that formation of high-molecular-weight complexes is a major mechanism
      increasing the RNA affinity for phospholipid membranes. The role of RNA-membrane
      interactions in early evolution is discussed in terms of the RNA world
      hypothesis.

PMID- 12068637
TI  - [Ribosomal protein binding with the first intron of the human ribosomal protein
      S26 pre-mRNA stimulates its interaction with proteins extracted from Hela cells].
AB  - As shown by nitrocellulose filtration assays with RNA fragments transcribed from
      various regions of the human ribosomal protein (rp) S26 gene, proteins of the 40S
      ribosome subunit bind to the first intron of the rpS26 pre-mRNA. The binding
      involved mostly S23, S26 and, to a lesser extent, S13/16. Negligible binding was
      observed for S2/3a, S6, S8, S10, S11, and S20. Small-subunit proteins did not
      affect the efficiency of in vitro splicing of a pre-mRNA fragment corresponding
      to the first intron, second exon, second intron, and a part of the third exon of
      the rpS26 gene. However, ribosomal proteins substantially increased UV-induced
      adduction of the pre-mRNA fragments with nuclear extract proteins of HeLa cells.
      The same set of HeLa proteins was observed with each pre-mRNA fragment. Ribosomal
      proteins formed adducts only in the absence of HeLa proteins.

PMID- 12068638
TI  - [Interaction of topotecan, DNA topoisomerase I inhibitor, with double-stranded
      polydeoxyribonucleotides. III. Binding at the minor groove].
AB  - Interaction of topotecan (TPT) with calf thymus DNA, coliphage T4 DNA, and
      poly(dG-dC). poly(dG-dC) was studied by optical (linear flow dichroism, UV-vis
      spectroscopy) and quantum chemical methods. The linear dichroism (LD) signal of
      TPT bound to DNA was shown to have positive sign in the range 260-295 nm. This
      means that the plane of quinoline fragment (rings A and B) of TPT molecule form
      an angle lower 54 degrees with the long axis of DNA, and hence TPT molecule can
      not intercalate between DNA base pairs. TPT was established to bind to calf
      thymus DNA as readily as to coliphage T4 DNA whose all cytosines in the major
      groove were glycosylated at the 5th position. Consequently, the DNA major groove
      does not participate in TPT binding. TPT molecule was shown to compete with
      distamycin for binding sites in the minor groove of DNA and poly(dG-dC). poly(dG
      dC). Thus, it was demonstrated for the first time that TPT binds to DNA at its
      minor groove.

PMID- 12068639
TI  - [HMG1 domains: the victims of circumstance].
AB  - The method of circular dichroism (CD) was used to compare DNA behavior during its
      interaction with linker histone H1 and with non-histone chromosomal protein HMG1
      at different ionic strength and at different protein content in the system. The
      role of negatively charged C-terminal fragment of HMG1 was analyzed using
      recombinant protein HMG1-(A + B), which lacks the C terminal amino acid sequence.
      The psi-type CD spectra were common for DNA interaction with histone H1, but no
      spectra of this type were observed in HMG1-DNA systems even at high ionic
      strength. The CD spectrum of the truncated recombinant protein at high salt
      concentration somewhat resembled the psi-type spectrum. Two very intense positive
      bands were located near 215 nm and near 273 nm, and the whole CD spectrum was
      positive. The role of C-terminal tail of HMG1 in formation of the ordered DNA
      protein complexes is discussed.

PMID- 12068641
TI  - [Differences in receptor specificity between the influenza A viruses isolated
      from the duck, chicken, and human].
AB  - The affinity of the duck, chicken, and human influenza viruses to the host cell
      sialosides was determined, and considerable distinctions between duck and chicken
      viruses were found. Duck viruses bind to a wide range of sialosides, including
      the short-stem gangliosides. Most of the chicken viruses, like human ones, lose
      the ability to bind these gangliosides, which strictly correlates with the
      appearance of carbohydrate at position 158-160. The affinity of the chicken
      viruses to sialoglycoconjugates of chicken intestine as well as chicken, monkey,
      and human respiratory epithelial cells exceeds that of the duck viruses. The
      human influenza viruses have high affinity to the same cells but do not bind at
      all to the duck epithelial cell. This testifies to the absence of 6'
      sialylgalactose residues from the duck cells, in contrast to chicken and monkey
      cells. The alteration of the receptor specificity of chicken viruses in
      comparison with duck ones results in the similarity of the patterns of accessible
      cells for chicken and human influenza viruses. This may be the cause of the
      appearance of the line of H9N2 viruses from Hong Kong live bird markets with
      receptor specificity similar to that of H3N2 human viruses, and of the ability of
      H5N1 and H9N2 chicken influenza viruses to infect humans.

PMID- 12068640
TI  - [Formation of liquid-crystalline dispersions of double-stranded DNA-chitosan
      complexes].
AB  - Right-handed helical double-stranded DNA molecules were shown to interact with
      chitosans to form under certain conditions (chitosan molecular weight, content of
      amino groups, distance between amino groups, ionic strength and pH of solution)
      cholesteric liquid-crystalline dispersions characterized by abnormal positive
      band in CD spectrum in the absorption region of DNA nitrogen bases. Conditions
      were found for the appearance of intense negative band in CD spectrum upon
      dispersion formation. In some cases, no intense band appeared in CD spectrum in
      spite of dispersion formation. These results indicate not only the multiple forms
      of liquid-crystalline dispersions of DNA-chitosan complexes but also a
      possibility to control the spatial properties of these complexes. The
      multiplicity of liquid-crystalline forms of DNA-chitosan complexes was attempted
      to explain by the effect of character of dipoles distribution over the surface of
      DNA molecules on the sense of spatial twist of cholesteric liquid crystals
      resulting from molecules of the complexes.

PMID- 12068642
TI  - [In memorium of Max Perutz (1914-2002)].

PMID- 12068643
TI  - [Max Perutz].

PMID- 12068644
TI  - The pediatric diabetes educator.

PMID- 12068645
TI  - Nutrient intake of adolescents with diabetes.

PMID- 12068646
TI  - Use of prayer in diabetes self-management.

PMID- 12068647
TI  - Put into practice.

PMID- 12068648
TI  - Impact of a multidisciplinary education program for children and adolescents with
      type 2 diabetes.

PMID- 12068649
TI  - A systematic literature review of the effectiveness of diabetes education of
      school personnel.
AB  - PURPOSE: This paper describes current knowledge levels of school personnel about
      diabetes, discusses the findings of a systematic review of the literature on the
      effectiveness of diabetes educational interventions for school personnel, and
      presents recommendations for future research. METHODS: English language
      literature published between January 1966 and May 2001 regarding the
      effectiveness of diabetes education of school personnel was systematically
      reviewed using multiple electronic databases. RESULTS: Four studies that examined
      the effectiveness of diabetes education of school personnel were identified. One
      study demonstrated improvement in teacher knowledge of treatment, another
      reported significant improvement in comprehensive knowledge scores, and a third
      study demonstrated significant knowledge deficits across 4 measures of teacher
      knowledge about diabetes. A fourth study demonstrated a decrease in the
      cumulative frequency of diabetic ketoacidosis. CONCLUSIONS: The literature
      regarding the effectiveness of diabetes education of school personnel is scant,
      the methodology is inadequate, the results are mixed, and the focus is on a
      narrow range of outcomes. Further research is needed to define effective
      interventions for improving the health and quality of life of school-age children
      and adolescents with diabetes.

PMID- 12068650
TI  - Prevention of overweight and obesity in children: influences on the food
      environment.
AB  - PURPOSE: There is an epidemic of pediatric overweight and obesity leading to type
      2 diabetes in youth. The purpose of this review is to describe the multiple paths
      of influence on the food environment of youth and to identify diabetes education
      strategies focused on early prevention of overweight and obesity. METHODS: A
      review of relevant professional literature was conducted. RESULTS: Models of
      obesity prevention in youth need to address genetic factors that influence the
      development of food preferences in the young child, parenting influences on
      eating pattern development, and access and availability of foods in the physical
      environment of the child. CONCLUSIONS: Early intervention with parents of young
      children is required to prevent the development of eating patterns that lead to
      pediatric obesity and type 2 diabetes in youth. Diabetes educators need to be
      able to inform parents of the multiple paths of influence on the food environment
      of the child and suggest strategies to encourage the development of positive food
      preferences and intake.

PMID- 12068651
TI  - Nocturnal polyuria in type 2 diabetes: a symptom of obstructive sleep apnea.
AB  - PURPOSE: Polyuria and nocturia in individuals with type 2 diabetes may be due to
      obstructive sleep apnea (OSA), a recently recognized etiology of excess nighttime
      urine production. This exploratory study examined the relationships among glucose
      control, OSA, and nocturnal urine production. METHODS: A sample of community
      dwelling older adults (20 nondiabetic subjects and 10 poorly controlled type 2
      diabetes subjects) was recruited based on self-report of nocturia more than twice
      per night. Participants were monitored on a metabolic research unit for 24 hours
      to track intake/output, collect blood and urine samples, and conduct an overnight
      polysomnography sleep study. RESULTS: None of the subjects had fasting serum
      glucose levels above the renal threshold. OSA was found in 65% of subjects. Those
      with moderate/severe OSA had significantly greater overnight urine production
      than subjects without OSA. Subjects with type 2 diabetes and moderate/severe OSA
      had the highest nocturnal urine production. CONCLUSIONS: The high incidence of
      undetected OSA in subjects with type 2 diabetes with nocturia suggests that
      nocturia, OSA, and type 2 diabetes frequently coexist and may be interrelated.

PMID- 12068652
TI  - [Parenting styles; determining factors in children's development and in their
      capacity to face disease and hospitalization].

PMID- 12068653
TI  - [Dementia: new challenge for intervention and research in nursing].

PMID- 12068654
TI  - [Salt consumption, arterial pressure, morbidity, and mortality].

PMID- 12068655
TI  - [The stem cell promise].

PMID- 12068656
TI  - [Prescribing compression treatment in leg ulcers].

PMID- 12068657
TI  - [Several populations may decrease in about half in the next 50 years].

PMID- 12068658
TI  - [Electromagnetic fields at home have leukemia risks for children].

PMID- 12068659
TI  - [Ethical features of nursing care at the end of life].

PMID- 12068660
TI  - [Helping relationship with the cardiac patient].

PMID- 12068661
TI  - [Modesty and body -- limits of the being].

PMID- 12068662
TI  - [Birth at the hospital].

PMID- 12068663
TI  - [Care of severe burns at the emergency service].

PMID- 12068665
TI  - [Parenteral/enteral feeding].

PMID- 12068664
TI  - [Health-related behaviors].

PMID- 12068666
TI  - [Damien].

PMID- 12068667
TI  - [The improvement of the reimbursement costs of mental health of psychiatric
      patients].

PMID- 12068668
TI  - [What is the status of the adolescents?].

PMID- 12068669
TI  - [Therapeutic environment: when it is necessary to wait].

PMID- 12068670
TI  - [The misfortune raft: a savior-totem?].

PMID- 12068671
TI  - [The clinical process. Nursing of the adolescent in depression].

PMID- 12068672
TI  - [Conversation].

PMID- 12068673
TI  - [Perspectives: parenting to the adolescent today].

PMID- 12068674
TI  - [Clinical process. Manic behavior during the antidepressant treatment of bipolar
      patients].

PMID- 12068675
TI  - [will the new law on the rights of the mentally ill take mental aspects into
      consideration?].

PMID- 12068676
TI  - [The first contrasting statement of the new decree concerning professional
      conduct].

PMID- 12068677
TI  - [Loneliness at the end of life, suffering both for the dying person and the
      caregiver].

PMID- 12068678
TI  - [Networks for the service of the elderly].

PMID- 12068680
TI  - [90% of people with apnea survive without knowing it].

PMID- 12068679
TI  - [Home treatment of chronic pain in the elderly].

PMID- 12068682
TI  - [Keeping company. Measures and new practices for funerals].

PMID- 12068681
TI  - [Sociology. Towards a new approach to death].

PMID- 12068683
TI  - [Keeping company. The mourning process, a difficult inner experience].

PMID- 12068684
TI  - [Keeping company. The loss of the aged partner].

PMID- 12068685
TI  - [Keeping company. The death of an ancestor].

PMID- 12068686
TI  - [Professional practice. The geriatrics work, in search of sense].

PMID- 12068688
TI  - [Animation. Maintaining the aging memory].

PMID- 12068687
TI  - [Care strategy. Screening of deglutition disorders in the elderly].

PMID- 12068689
TI  - [Geriatric nursing care and Internet].

PMID- 12068690
TI  - [Prevention and treatment of pressure ulcers of adults and elderly persons].

PMID- 12068691
TI  - ["Because improper aging is not unavoidable!"].

PMID- 12068692
TI  - [21st century, towards what kind of end of life?].

PMID- 12068693
TI  - [Dependence, when it has you under its grips...].

PMID- 12068695
TI  - [5th Meeting of oncology nurses].

PMID- 12068696
TI  - [Words of the world. Haiti, a critical health status].

PMID- 12068694
TI  - [Diabetes and pregnancy in the country of stocks].

PMID- 12068697
TI  - [Patient's education. Value of the determination of capillary glycemia].

PMID- 12068698
TI  - [Physiopathology. Addictive drugs, current definitions].

PMID- 12068699
TI  - [Public health. Drug addiction and health policy].

PMID- 12068700
TI  - [Current neurobiological data on drugs].

PMID- 12068701
TI  - [Therapeutic strategy. Replacement treatments for drug addicts].

PMID- 12068702
TI  - [Care strategy. Hospitalization of drug addicts].

PMID- 12068703
TI  - [The caregiver-patient relation in drug addiction].

PMID- 12068704
TI  - ["Please, make a drawing of dependence for me..."].

PMID- 12068706
TI  - [Current pathways of health safety].

PMID- 12068705
TI  - [Perspectives. To warn young people means to save the future].

PMID- 12068707
TI  - A tribute to Nancy Caroline, MD, & emergency care in the streets. Interview by
      Bryan E. Bledsoe and Mick J. Sanders.

PMID- 12068708
TI  - Case of the month. Crane collapse.

PMID- 12068709
TI  - Off track. Four die in Amtrack auto train derailment.

PMID- 12068711
TI  - EMS at home in the operating room. Lincoln EMS implements a comprehensive
      approach to airway management.

PMID- 12068710
TI  - Endotracheal rules of engagement. How to reduce the incidence of unrecognized
      esophageal intubations.
AB  - With evidence that esophageal intubations happen frequently in EMS and of the
      possible resulting catastrophic effects, an EMS system should carefully consider
      the way it handles this problem. With the introduction of better ways to
      determine placement, a willingness to investigate thoroughly and the ET Rules of
      Engagement, UEI rates can be consistently low.

PMID- 12068712
TI  - LMA fastrach. EMS discovers the intubating laryngeal mask airway.

PMID- 12068713
TI  - Bad breaks. Keep the priority & care of orthopedic injuries in proper
      perspective.
AB  - The recognition and appropriate emergency management of orthopedic emergencies is
      essential to minimize damage and optimize outcome. Priorities, principles and
      good judgment can make a difference in the overall outcome for the injured
      patient. These orthopedic emergencies require a team approach to assessment and
      care. Therefore, collaboration with other EMS providers, nurses, physicians,
      surgeons and other health-care personnel is essential to the proper care of the
      patient.

PMID- 12068714
TI  - Acute abdominal emergencies. Assessing & treating patients with severe abdominal
      pain.
AB  - A focused approach to the patient with abdominal pain includes a working
      knowledge of relevant anatomy, a basic understanding of physiology and the
      ability to take a careful history. Creating a differential diagnosis,
      resuscitating patients in shock and appropriately treating a patient's pain will
      allow EMS crews to greatly impact patient care.

PMID- 12068715
TI  - [Sterility of males determined by functional features of the mouse spermatozoa
      bearing t-complex].
AB  - The mechanisms underlying normal spermatogenesis and its pathology expressed as
      male sterility determined by t-complex located on chromosome 17 in mice are
      considered in this review. t-Complex is a very convenient model with diverse
      markers of expression of the genes involved in development of the functional
      features of the spermatozoa bearing t-complex. These features include defects of
      mobility, capacitation, and acrosome reactions, which determine full or partial
      male sterility. It has been proposed that the defects of capacitation are also
      inherent in humans and affect male fertility. This homology is confirmed by the
      presence of the male gene Tcp11 in humans and demonstration of the fact that the
      protein TCP11 plays a leading role in modulation of the capacitation of murine
      spermatozoa. Hence it follows that the defects of human genes leading to
      incomplete binding of the fertilization promoting peptide could play a certain
      role in a decreased male fertility. All this is essential not only for deeper
      understanding of the biology of spermatozoa, but also for development of new
      therapeutic methods of finding and treating the semen pathology.

PMID- 12068716
TI  - [Production of regenerants in sugar beet].
AB  - The experimental results are presented on production of plants-regenerants of the
      sugar beet (Beta vulgaris L.) via callus formation or direct organogenesis from
      the leaf tissues. The method of aseptic treatment was developed for the seeds
      with strong bacterial and fungal invasion. The regenerant plants were obtained in
      the presence of various concentrations of synthetic hormones, such as cytokinin
      (6-benzaminopurine) and auxin (naphthylacetic acid), and inhibitor of auxin
      transport in plants (2,3,5-triiodobenzoic acid). This combination of growth
      regulators made it possible to avoid callus formation. The genotype of initial
      plants affected the capacity for callus formation and regeneration. The
      temperature influenced rhizogenesis in regenerants.

PMID- 12068718
TI  - [The source of transitory innervation of suprachiasmatic nucleus by tyrosine
      hydroxylase-immunoreactive fibers during the postnatal period in rats].
AB  - Suprachiasmatic nucleus in the rats during early postnatal development is
      transitorily innervated by tyrosine hydroxylase-immunoreactive fibers that are
      neither catecholamine- nor serotoninergic. The goal of this immunocytochemical
      investigation was to find out if tyrosine hydroxylase-immunoreactive neurons of
      anterior hypothalamus could be the source of this innervation. According to the
      obtained immunocytochemical data, multiple multipolar tyrosine hydroxylase
      immunoreactive neurons are localized around the suprachiasmatic nucleus in the
      rats at days 2 and 10 of postnatal development. Most of them were observed
      ventrally and laterally to the nucleus. The axons of the neurons are oriented
      towards the suprachiasmatic nucleus. Further investigation demonstrated
      considerably decreased number of tyrosine hydroxylase-immunoreactive neurons
      surrounding the suprachiasmatic nucleus in the adult animals as compared to early
      postnatal period, which correlates to the number of tyrosine hydroxylase
      immunoreactive fibers in this nucleus. Hence, tyrosine hydroxylase-immunoreactive
      neurons in the ventral region of anterior hypothalamus can be considered as a
      potential source of transitory innervation of suprachiasmatic nucleus by tyrosine
      hydroxylase-immunoreactive fibers during early postnatal development.

PMID- 12068717
TI  - [Proliferation of primary human keratinocytes during histogenesis in culture].
AB  - We studied formation of epithelial cysts during cultivation of the primary
      keratinocytes in a collagen gel. Two stages--epithelial spheroid and cysts--can
      be recognized in the histogenesis process. Keratinocyte migration prevails at the
      initial stages of morphogenesis. The stage of spheroid can be described by active
      cell proliferation. Stratification of spheroid epithelium takes place at the
      stage of epithelial cysts, while the rate of keratinocytes proliferation
      decreases. Formation of epithelial cysts is induced by morphogene(s) of
      mesenchymal origin. The obtained data indicate partial dissociation of
      keratinocyte proliferation and migration during cytogenesis.

PMID- 12068719
TI  - [Formation of basal bodies in the ciliary epithelium of molluscs Buccinum undatum
      L. and Lymnaea stagnalis L].
AB  - Electron microscopic studies of the leg ciliary epithelium was carried out in two
      mollusks. In the epithelium of the leg of adult animals, the centrioles were
      mostly formed de novo with participation of deuterosomes during the formation of
      basal bodies. Transformation of the centriolar cylinder in a mature basal body is
      accompanied by the cylinder elongation and appearance of pericentriolar
      structures, such as rootlet system, basal legs, and basal plate. Centriolegenesis
      proceeds in both ciliate and nonciliate (with microvilli) cells of the
      epithelium. It has been proposed that the cell with microvilli represent a
      transitional stage in differentiation of the ciliary cells.

PMID- 12068720
TI  - [Effect of homologous peptides of differentiation factors HLDF and PEDF on
      preimplantation development of mice in vitro].
AB  - We studied the effect of synthetic peptides PEDF-6 and HLDF-6 on preimplantation
      development of mouse embryos in vitro. PEDF-6 peptide corresponds to fragment 351
      356 and of pigment epithelium-derived differentiation factor (PEDF), while HLDF-6
      peptide corresponds to fragment 84-89 of differentiation factor HLDF isolated
      from HL-60 cell line. Despite high homology, these peptides had different effects
      on the early development. PEDF-6 had no effect on the cleavage of 2-4-cell
      embryos but decelerated blastocyst formation from such embryos and disturbed
      their structure. In the presence of HLDF-6 the blastomeres divided more actively
      as compared to the control and a higher number of embryos developed to the
      blastocyst stage. The effects of both peptides were stage-specific: the affect
      the embryos at early cleavage stages and, apparently, determine their further
      development at that moment although do not directly affect formation of the
      blastocysts.

PMID- 12068721
TI  - [In vitro maturation of cattle oocytes taken from ovaries with different
      morphofunctional states].
AB  - We studied the capacity of cattle oocytes taken from ovaries with different
      morphofunctional state for development to metaphase 2 in vitro. A classification
      of ovaries has been proposed according to their morphofunctional state: (1)
      ovaries with a yellow body from the last cycle, without dominating follicle, with
      many follicles of varying diameter; (2) ovaries with a yellow body from the last
      cycle, with dominating follicle (from 10 mm in diameter); (3) ovaries with a
      large functioning yellow body and follicles of varying diameter; (4) ovaries with
      a follicular cystoid formation (more than 25 mm in diameter); (5) ovaries with a
      yellow body from past cycles and small (1-2 mm) follicles, supposedly with a
      weakened hormonal function. It was shown that the morphofunctional state of
      ovaries determined the total number of oocytes isolated from an ovary and number
      of morphologically normal oocytes feasible for cultivation. At the same time, no
      reliable differences in the capacity for extrusion of the first polar body
      between the oocytes from the ovaries of different types were found in the
      experiments on in vitro oocytes maturation. Since the coefficient of correlation
      between the extrusion of the first polar body and maturation to metaphase 2 was
      in 0.95, there is every reason to believe that the capacity for development to
      metaphase 2 does not depend on the morphofunctional state of ovaries.

PMID- 12068722
TI  - [Structural abnormalities of hippocampus in 101/HY mice].
AB  - We studied cytoarchitectonics of the hippocampus in 101/HY and CBA mice on brain
      sections stained after Nissl and Timm. In CBA mice, the structure of hippocampus
      was normal. In 10/HY mice, stratum pyramidale in field CA3 was "splitted" and the
      density of pyramidal neurons was decreased. Abnormalities were also found in the
      zone of suprapyramidal projections of mossy fibers (sp-ME), i.e., terminals of
      axons of the fascia dentata granular cells on the apical dendrites of pyramids.
      If in CBA mice the sp-MF zone was normal, i.e., looked like a vast compact
      formation or dense ordered bundle, in 101/HY mice, the sp-MF zone represented a
      group of scattered, diffuse, and interrupted bundles of varying length, some of
      which were incorporated in stratum pyramidale. Possible causes of the described
      morphological abnormalities are discussed, as well as their relation to specific
      features of biology, behavior, and neurological status of 101/HY mice.

PMID- 12068723
TI  - [Statistical and frequency-amplitude characteristics of ultra weak emissions of
      the loach eggs and embryos under the normal conditions and during their optic
      interactions. I. Characteristics of ultra weak emission in normal development and
      the optic role of egg envelope].
AB  - Ultraweak emissions of groups comprising several dozens of unfertilized and
      fertilized loach eggs, embryos, larvae, and their egg envelopes were measured on
      a photomultiplier tube. The envelopes absorbed the light from external sources
      but readily gave it back in the absence of embryos. We carried out statistical
      and frequency-amplitude analyses of ultraweak emissions and studied the
      autocorrelation structure of their frequency spectra. The frequencies of signals
      with different intensity underwent regular changes during development. Cascades
      of short-term (< or = 1 ms) flashes timed (during cleavage) to furrowing were a
      characteristic element of ultraweak emission. The Fourier spectra of developing
      embryos had pronounced frequency-amplitude peaks and higher, than in unfertilized
      eggs and inanimate samples, mutual correlation during successive time intervals.
      Stage-specific translational symmetry of the frequency spectra of ultraweak
      emissions was demonstrated, which suggests the presence in groups of embryos of a
      coordinated system of harmonic oscillators. The latter underwent regular changes
      during development. The measurement of ultraweak emissions represents a unique
      non-invasive method of analysis of these oscillators.

PMID- 12068724
TI  - [Isozyme patterns of lactate dehydrogenase from tissues of mink and arctic fox
      during postnatal development].
AB  - Isozymes of lactate dehydrogenase extracted from heart, kidney, and liver of mink
      (Mustela vison Briss.) and Arctic fox (Alopex lagopus L.) during postnatal
      development were separated by agarose gel electrophoresis. Tissue-specific
      isozyme pattern of lactate dehydrogenase can be revealed at the age of one month,
      while the definitive pattern is formed at the age of four months. The isozyme
      patterns of lactate dehydrogenase in the studied tissues of mink and Arctic fox
      share the properties specific for animal species of various ecogenesis.

PMID- 12068725
TI  - [Synaptic contacts of neurons of fascia dentata transplants with nonspecific
      targets in neocortex of recipients].
AB  - We carried out an electron microscopy study of possible synaptic contacts of the
      neurons of intracortical transplants of the rat brain fascia dentata with targets
      in the recipient somatosensory cortex. The axons of fascia dentata granular cell
      and their synaptic terminals could be easily identified in the neocortex due to
      their distinct morphological features (mossy fibers), although the fascia dentate
      cells normally do not interact with the neocortex. Thin nonmyelenized mossy
      fibers were found in both an intermediate zone between the transplant and brain
      and in the adjacent brain. Their presynaptic buds, like in situ, had large size
      and formed characteristic terminal, intraterminal, and en passant multiple
      synaptic contacts and desmosome-like junctions. The aberrant nerve fibers used
      perykaryons, dendrites of varying diameter, and dendrite spikes of the
      somatosensory cortex pyramidal neurons as postsynaptic targets in the neocortex.
      In addition to vacant spaces that appeared in the brain as a result of
      transplantation, the ingrowing axons induced the formation of additional contact
      sites: deep invaginations of the plasmalemma of perykaryons, somatic spikes,
      terminal branchings of dendrites, and dendritic outgrowths of complex branched
      shape. These aberrant contacts were characterized by the presence of
      polyribosomes, endoplasmic reticulum cisternae, and mitochondria in the
      postsynaptic loci. Osmiophility and extension of desmosome-like junctions were
      also enhanced in such synapses. Thus, it was shown that mossy fibers ingrowing in
      the recipient neocortex were capable of forming cell-to-cell contacts with signs
      of functional synapses to atypical cell targets.

PMID- 12068726
TI  - What is fueling the increase in health care costs?

PMID- 12068727
TI  - Urgent agenda for health care: CEOs tackle core issues. Health care at a critical
      juncture.

PMID- 12068728
TI  - Urgent agenda for health care: CEOs tackle core issues. Rebuilding relationships
      with physicians.

PMID- 12068729
TI  - Rising health care costs: employers respond.

PMID- 12068730
TI  - Health plans mobilize national bioterrorism response.

PMID- 12068731
TI  - Technology drives a medical revolution. Online systems facilitate practice of
      evidence-based medicine.

PMID- 12068732
TI  - Provider report cards: who's best at the service I need?

PMID- 12068733
TI  - Improving patient safety. Support systems help prevent medical errors.

PMID- 12068734
TI  - Confronting a flawed legal philosophy. In health care, solutions depend on
      balancing individual claims and the common good.

PMID- 12068735
TI  - Just a phone call. When member communication becomes a lifeline.

PMID- 12068737
TI  - The cost of building an information highway. Was $18 billion too much? Too
      little?

PMID- 12068736
TI  - Immunizing our children. The challenges to meeting the Healthy People 2010 goal.

PMID- 12068738
TI  - [Guidelines of the German Society of Gastroenterology for the treatment of
      gallstones].
AB  - The vast majority of gallbladder stones are cholesterol stones. The natural
      course taken by these stones is benign. Only patients with symptomatic gallstones
      require treatment, mostly in the form of laparoscopic cholecystectomy. Unlike
      gallstones, bile duct stones are treated during their symptomatic and
      asymptomatic stages. Endoscopic sphincterotomy is the treatment of choice for
      cholecystectomised patients. If patients have concomitant gallstones they should
      receive endoscopic sphincterotomy first (therapy splitting), at least according
      to the German consensus. Obstructive cholangitis should always be treated with
      endoscopic drainage procedures first.

PMID- 12068739
TI  - [Coloretal cardinoma--prevention, screening and endoscopic therapy].
AB  - Colorectal cancer (CR) is the second leading cause of cancer-related deaths in
      Germany. Screening strategies have been shown to be effective in reducing CRC
      mortality. One priority has to be identifying persons at increased risk of
      developing CRC. Family history is one important factor. Persons at risk of
      developing hereditary forms of CRC have to be included in specially-adapted
      surveillance schemes. To increase the efficacy of the surveillance programs the
      co-operation of the population at large must be improved. As 90 percent of
      colorectal carcinomas arise from adenomas, a consistent and rigorous polypectomy
      will lead to a reduction in CRC incidence. Persons with adenomas have an
      increased risk of recurrence after polypectomy and should hence be followed up.
      If the removed polyp contains a carcinoma further measures depend on its histo
      pathological staging.

PMID- 12068740
TI  - [Therapy of Crohn disease according to the guidelines of the German Society for
      the treatment of digestive and metabolic diseases].
AB  - Crohn's disease is still an incurable affliction: While various pathogenic
      mechanisms have been elucidated in detail, the etiology remains undetected.
      Conservative medical management is the mainstay of treatment with corticosteroids
      and azathioprin as pivotal drugs. Aminosalicylates are of minor importance.
      Infliximab may be effective for individual patients as a third line of treatment
      after failure of classical immunosuppression or when a rapid response is
      mandatory in a corticosteroid-resistant situation. Its long-term efficacy and
      safety in the treatment of fistulae is unknown. Antibiotics and nutritional
      measures may be of help in certain clinical conditions. Satisfactory means of
      maintaining remission in inactive patients is not available to date.
      Psychotherapy may be useful in helping patients to cope but does not
      significantly affect the course of the disease. The guidelines presented here are
      based on a consensus developed by the Deutsche Gesellschaft fur Verdauungs- und
      Stoffwechselkrankheiten in 1996 (26), updated in December 2001 (to be published)
      on the basis of recent randomized trials and meta-analyses.

PMID- 12068741
TI  - [Evidence-based guideline for the diagnosis and treatment of ulcerative colitis].
AB  - The therapy of ulcerative colitis is still not causal but is directed
      unspecifically at mucosal inflammation. The treatment of the uncomplicated
      remitting course is tailored to the activity and location of the disease. In the
      case of mild to moderate activity aminosalicylates are recommended, in the
      absence of a response systemic steroids are the treatment of choice. However,
      when administered locally, aminosalicylates have proven superior to steroids.
      Chronic active disease should be treated with azathioprine. A steroid-refractory
      course often responds to ciclosporine or tacrolimus: A course refractory to
      conservative measures is an indication for a proctocolectomy with ileoanal
      anastomosis.

PMID- 12068742
TI  - [General practice in a modern health care system--consequences for medical
      research, education and practice].
AB  - This first of two articles describes the far-reaching changes to the practice and
      theory of general practice that are leading from the old-style general
      practitioner changing to the modern-day primary health care specialist. These
      already partly accomplished changes, whilst bringing into focus the future role
      of general practice in a modern health care system, are altering the self
      awareness of the profession and the way it defines itself. Specifics of the
      theory and practice of decision-making in primary health care, within this
      context of vital importance but as yet barely taken into account, are explained
      on the basis of Bayes' theorem and with the aid of examples of empirical data on
      the rational diagnosis of thyroid dysfunction. Making use of examples of coronary
      heart disease diagnostics, the second part of this article illustrates important
      differences between health care-service levels and the consequences arising from
      these differences for medical research, education and practice.

PMID- 12068743
TI  - [Familial pancreatic cancer--concept for study of the National Case Collection
      and early diagnosis program for high risk people].
AB  - Ductal pancreatic cancer is a public health problem on the increase. The
      lethality and incidence of this disease are almost identical. A number of these
      cancers cluster in families. By definition, pancreatic cancer appearing in at
      least two first degree relatives is named familial pancreatic cancer (FPC). The
      "National Case Collection Familial Pancreatic Cancer" (FaPaCa) was founded at the
      Philipps University of Marburg, Germany, in July 1999 within the scope of the
      project "Clinical and genetic examinations of familial exocrine pancreatic cancer
      including the foundation of a national case collection" (http://www.med.uni
      marburg.de/fapaca). The aims of this project are 1 to evaluate the share of FPC
      of all pancreatic cancers by performing a multi-centered study, 2 to identify
      epidemiological risk factors that predispose to pancreatic cancer in these
      families, 3 to identify families with a likely genetic predisposition to
      pancreatic cancer, 4 to offer a screening program for high risk individuals in
      these families, which is to be evaluated in an observational study, and finally
      to identify presumed genetic defects that predispose to pancreatic cancer in FPC
      families. This manuscript presents the scientific concept behind the FaPaCa
      project and reports on its attendant screening program for FPC families.

PMID- 12068744
TI  - [Communication among physicians--impact, quality and requirements of discharge
      and referral letters].
AB  - Discharge and referral letters are essential for the communication among
      physicians. In contrast to Anglo-American research this issue has not received
      much attention in Germany, until now. For many years deficiencies in the quality
      of letters have been internationally reported in all medical specialist
      publications; these deficiencies relate in particular to the speed of delivery
      and the length of the discharge letters. Rapidly delivered, well-structured
      letters, one or two pages in length, with relevant information for outpatient
      care are preferred by physicians in private practice. The diagnosis, the results
      of examinations, lists of medications, and the suggestions made for treatment
      after discharge are essential items of information. The requirements mentioned
      with regard to discharge letters also apply to referral letters. From the point
      of view of clinicians, details about actual medications, suicidal
      tendency/aggression, current problems, the reason(s) for referral, drug
      intolerance and somatic disorders are felt to be indispensable. Details
      concerning guardianship, previous therapy, substance misuse, phone numbers of
      relatives, prior examinations, diagnoses, and previous examination findings are
      considered most important.

PMID- 12068745
TI  - The pathogenetic significance of intestinal Candida colonization--a systematic
      review from an interdisciplinary and environmental medical point of view.
AB  - The etiological significance of intestinal Candida colonization continues to be
      controversial. This is a systematic review to determine the pathogenetic
      significance of intestinal Candida colonization. The search was essentially
      performed from 1990 to 12/7/2000 in Medline and the Cochrane-Library. The data
      source was restricted to articles in English and German. Selection criteria
      covered the topics "Epidemiology", "Infectious Diseases", "Candida-Syndrome" and
      "Therapy" and were essentially confined to in-vivo examination of immunocompetent
      adults. Two reviewers extracted independently data using predefined criteria. In
      total, 96 citations that proved suitable for use in the systematic review were
      found. Depending on the localization in the gastrointestinal tract, the recovery
      technique employed, and transport times, Candida colonization is frequently
      detected in healthy, immunocompetent adults (prevalence: 4-88%). None of the
      studies available so far furnish any evidence that nutritional factors, food
      additives, pollutants, anti-ovulants, other types of medication or diabetes
      mellitus might be predisposing factors for intestinal Candida colonization.
      However, therapeutic studies point to the possibility of Candida playing a role
      in antibiotic-associated diarrhea. On the other hand, antibiotics seem to favor
      bacterial dysbiosis, and this, like the direct side effects of drugs, offers a
      more plausible explanation for diarrhea or gastrointestinal symptoms. The role of
      intestinal colonization by Candida in Candida-associated vulvovaginitis and IgE
      mediated disorders remains contradictory. Nevertheless, neither epidemiological
      nor therapeutic studies provide evidence for the existence of the so-called
      "Candida-syndrome" or "Candida-hypersensitivity-syndrome". At present, there are
      no proven treatment indications for antifungal "bowel decontamination".

PMID- 12068746
TI  - Fungal flora in groundwater-derived public drinking water.
AB  - In order to assess the dissemination of hygienically relevant fungi via the
      public drinking water distribution system, a 12-month survey was performed on
      groundwater-derived drinking water from 29 water supplies in North Rhine
      Westphalia, Germany. Frequencies of contaminated water samples, and the prevalent
      species and patterns of occurrence in raw water, waterworks, the network and
      house installations were studied on the basis of 2657 water samples. Results were
      obtained by long-term incubation of 1 ml aliquots of water samples on agar-based
      culture media, following bacteriological procedures documented in the German
      drinking water regulations (Anon, 1990). No correlation with standard hygiene
      indicators, such as E. coli or other coliform bacteria was observed. Common
      opportunistic and allergenic Aspergillus species were encountered only rarely.
      The fungal flora was dominated by a limited number of species of Acremonium,
      Exophiala, Penicillium and particularly Phialophora; some of them occurred
      throughout the entire drinking water system and are thought to constitute a
      resident fungal flora. Phialophora sp. nov., to be described as a new species
      elsewhere, was ubiquitous; it was found in 26.6% of the samples positive for
      fungi (7.5% of 2657). Fungal diversity in the network itself was significantly
      lower than in raw water and house installations, indicating that not all fungi
      gaining access to the system are capable of surviving for longer periods. For
      species such as Verticillium lecanii, found exclusively after the introduction of
      newly buried pipes and remaining localized at those sites, introduction via
      arthropod vectors is likely. The resident species of Phialophora, Exophiala and
      Acremonium are particularly significant as they are shown to be disseminated
      efficiently by public drinking water.

PMID- 12068748
TI  - Detection and response to a meningococcal disease outbreak following a youth
      football tournament with teams from four European countries.
AB  - An outbreak of meningococcal disease, caused by Neisseria meningitidis, occurred
      following an international youth football tournament in the summer of 1997,
      affecting individuals from four European countries. This paper describes the
      outbreak, focusing on international co-operation in detection, investigation,
      control and follow-up, identifying weaknesses and exploring opportunities for
      improved co-operation. Data came from interviews, reports and related documents.
      The detection and management of the outbreak in each country is analysed. Eleven
      cases were linked to this outbreak and serotyped as C:2a:P1.5. Control measures
      varied in each country, reflecting different national guidelines. The outbreak
      illustrated deficiencies in management of international outbreaks but also
      demonstrated benefits of international co-operation.

PMID- 12068747
TI  - Contamination of water supplies with Cryptosporidium parvum and Giardia lamblia
      and diarrheal illness in selected Russian cities.
AB  - Cryptosporidium parvum and Giardia lamblia are important agents of waterborne
      diarrheal illness worldwide. While giardiasis is routinely diagnosed in Russia
      with a chemical staining technique, data on the prevalence of cryptosporidiosis
      are scarce. Monitoring of the respective parasites in water supplies in Russia is
      very limited. A health survey conducted in the city of Cherepovets and three
      other cities in the European part of Russia using enzyme-linked immunosorbent
      assays (ELISA) demonstrated that 6.9% of diarrheal patients tested had C. parvum
      antigens in their fecal samples; 9.4% had G. lamblia antigens. A survey of
      occurrence of these parasites in water supplies in Cherepovets and seven other
      cities demonstrated that source and finished water samples from several of these
      cities were contaminated with either C. parvum oocysts or G. lamblia cysts. The
      surveys were not designed to assess associations between presence or
      concentrations of C. parvum and G. lamblia in water and related gastrointestinal
      diseases in exposed populations. Rather, the goals were to demonstrate the
      presence of disinfection-resistant protozoan parasites in untreated and treated
      waters, and the importance of these pathogens as causative agents of diarrheal
      illnesses in a number of Russian cities.

PMID- 12068749
TI  - German Environmental Survey 1998 (GerES III): environmental pollutants in blood
      of the German population.
AB  - The German Environmental Survey was conducted for the third time in 1998 (GerES
      III). The probability sample of about 4800 subjects was selected to be
      representative for the German population with regard to region (East-/West
      Germany), community size, age (18 to 69 years) and gender. Blood samples were
      taken from each study participant and questionnaires were used to get exposure
      related information. Cadmium, lead, mercury, hexachlorobenzene (HCB),
      hexachlorocyclohexane (alpha-HCH, beta-HCH, gamma-HCH), 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (p, p'-DDE) and polychlorinated biphenyls (PCB-138, PCB
      153, PCB-180) were analysed in whole blood to document the extent, distribution,
      and determinants of exposure of the general population to these substances. The
      geometric means of Cd, Pb, and Hg in blood amounted to 0.44, 31, and 0.58
      microgram/l, respectively. Smokers showed a Cadmium level of 1.1 micrograms/l and
      non-smokers a level of 0.28 microgram/l. The geometric mean of lead was higher in
      the blood of males than of females (36 micrograms/l vs. 26 micrograms/l). The
      concentration of mercury in blood depends on fish consumption and the number of
      teeth with amalgam fillings. The mean concentrations of HCB and p, p'-DDE in
      blood were 0.44 microgram/l and 1.6 micrograms/l, respectively. In East-Germany
      (the former GDR) the DDE concentration in blood was more than twice as high as in
      West-Germany. Geometric means for PCB were 0.42, 0.68 and 0.44 microgram/l for
      PCB-138, PCB-153, and PCB-180, respectively. A marked increase of HCB, DDE and
      PCB levels with age could be observed. alpha-HCH and gamma-HCH could be detected
      in 1.7% and 5.2% of the samples only. beta-HCH was quantified in 34% of the
      samples with a 95th percentile of 0.5 microgram/l.

PMID- 12068750
TI  - Prevalence of respiratory symptoms in school children and salivary IgA--an
      epidemiological study in a rural area of Northrhine-Westphalia, Germany.
AB  - An elevated frequency of wheezing was found in school children in a rural area of
      Northrhine-Westphalia, Germany (Duhme and Keil, Institut fur Epidemiologie und
      Sozialmedizin, Universitat Munster, Munster, Germany 1997). In this study the
      prevalence of wheezing was reinvestigated by including main influencing factors.
      A cross-sectional survey was performed in all school children visiting school
      classes 1, 2 and 7, 8 (n = 1161). Two corresponding questionnaires were used: a
      parental questionnaire and a questionnaire for self-completion by the children
      aged 12-15. The latter included the ISAAC video questionnaire. The levels of
      immunoglobulins A, G and M were determined in 995 saliva samples. Testing of lung
      function (whole body plethysmography before and after physical exercise) was
      performed in children with and without parent-reported wheezing in the last 12
      months (n = 377). Response rate (questionnaire: 93%) and participation rates
      (saliva samples: 86%, lung function tests: 93%) were high. Our study confirmed
      higher prevalence of asthmatic symptoms in children aged 6-8 in Ochtrup (13.2%)
      compared to children of the same age in Muenster (8.5% (Duhme et al., Eur.
      Respir. J. 11, 840-847, 1998)). However, in the age group 12-15 years the
      prevalence was significantly lower in Ochtrup (9.8%), when compared to the former
      investigation and in comparison to Muenster (former survey: 17.9%; Muenster:
      13.1%). Prevalence of wheezing was consistently higher in families with atopic
      disease. Additionally, history of respiratory disease, premature birth and
      presence of pets during 1st year of life showed a positive association with
      prevalence of wheezing. Mean salivary IgA levels were 61.4 (SD (standard
      deviation) 35.1, median: 53.7) mg/l in children aged 6-8 years and 83.4 (SD 39.0,
      median: 76.3) mg/l in children aged 12-15 years. No significant association
      between salivary immunoglobulins and wheezing was detected.

PMID- 12068751
TI  - First isolation of urease-positive thermophilic Campylobacter (UPTC) from crows
      (Corvus levaillantii) in Japan.
AB  - Two strains of urease-positive thermophilic Campylobacter (UPTC), designated YC98
      1 and YC98-2, were identified by biochemical characterization after isolation
      from the intestinal contents of crows around Yokohama City, Japan, in 1998. The
      biochemical characteristics of these strains were identical to those of strains
      described previously. Pulsed-field gel electrophoresis (PFGE) after separate
      digestion with ApaI, SalI, and SmaI of the genomic DNA from the two strains
      indicated that respective PFGE profiles were distinctly different and
      distinguishable from each other. This is the first report of the isolation of
      UPTC from crows (Corvus levaillantii).

PMID- 12068753
TI  - [Ageing, diet, and prostatic cancer].

PMID- 12068754
TI  - [ABO surface isoantigens as prognostic factor in urothelial cancer and the long
      arm of chromosome 9: from hope to the stark scientific reality].

PMID- 12068755
TI  - [Glomerular morphologic protection after acute ischemia through the
      administration of Surgiran: (PGE1 and Alfadex, glucose cyclic oligomer).
      Morphometric study].
AB  - OBJECTIVE: To quantify the morphologic protection of PGE1 on renal glomerulus
      following normothermic acute renal ischemia. METHODS: This experimental study was
      carried out in 48 adult male Wistar rats. A simple right nephrectomy was
      performed in all rats. The rats were divided into two groups: one group was
      perfused with PGE1 and the other group with saline solution immediately after
      acute renal ischemia, which was produced by non-traumatic vascular clamping. The
      ischemia times were 15 and 60 minutes. The recovery period ranged from 24 hours
      to 7 days. After this period the animals were anesthetized and sacrificed.
      Histological and morphometric analyses of the right kidneys of the control group
      and the left kidneys of the study group were performed. RESULTS: The mortality
      was 31% (18.5% for the group perfused with PGE1 and 11.4% for the group perfused
      with saline solution). Kidneys of rats perfused with saline solution weighed more
      than the kidneys of rats perfused with PGE1 (1.771 +/- 0.455 and 1.55 +/- 0.34,
      respectively). Acute tubular necrosis was observed after 60 minutes' ischemia and
      was more evident in the saline than in the PGE1 group. The morphometric study
      showed no significant differences between the control (normal) and the PGE1 group
      for glomerular diameter (p < or = 0.101), sphericity factor (p < or = 0.239),
      glomerular perimeter (p < or = 0.092) and glomerular volume (p < or = 0.059).
      However, significant differences were found between the control and the saline
      perfusion group for area (p < or = 0.000), diameter (p < or = 0.000), perimeter
      (p < or = 0.000) and volume (p < or = 0.000). CONCLUSIONS: Kidney weight after
      ischemia increased more in the saline than in the PGE1-treated group since the
      edema in the renal parenchyma is attenuated by the anti-inflammatory and
      cytoprotective effects of PGE1. The morphometric study showed that in comparison
      to saline, PGE1 exerts a cytoprotective effect, although it is not considerable.

PMID- 12068752
TI  - Bacteroides fragilis and Escherichia coli bacteriophages in human faeces.
AB  - Some bacteriophages found in human faeces are being evaluated as possible
      indicators of viral contamination of water. These bacteriophages include somatic
      coliphages and Bacteroides fragilis phages. The aims of this study were to
      determine the occurrence and concentrations of somatic coliphages and Bacteroides
      fragilis phages in the stools of a human population residing in eastern France (n
      = 193). Somatic coliphages were detected in 68% of the stools at a mean
      concentration of 4.3 x 10(3) PFU.g-1 and Bacteroides fragilis phages were
      detected in 11% of the stools at a mean concentration of 7 x 10(1) PFU.g-1.
      Statistical analysis showed no correlation between the phage concentration and
      the age or sex of the human subject.

PMID- 12068756
TI  - [Endoscopic surgery of stress urinary incontinence, using the Stamey needle].
AB  - OBJECTIVE: To describe the utility of endoscopic management of stress urinary
      incontinence with Stamey's needle. METHODS: 50 multiparas (2-8 deliveries; mean
      4) aged 26-72 years (mean 42) consulted for stress urinary incontinence. All
      patients were evaluated by the Valsalva maneuver, cough and perineal ultrasound
      and were classified as mild (8 cases), moderate (26 cases) and severe (16 cases).
      Thirty-eight patients had cystocele. Bladder neck suspension with Stamey's needle
      was performed in all patients. A cystostomy and not a urethrovesical catheter,
      was left indwelling in all patients. RESULTS: Multiparity and management at
      childbirth were the most common factors associated with stress urinary
      incontinence. Perineal ultrasound was found to be useful in the evaluation of the
      incontinent patient and the surgical procedure. The endoscopic procedure permits
      physiologic correction of stress urinary incontinence and cystocele. CONCLUSIONS:
      Endoscopic surgery with Stamey's needle reduces the operating time, length of
      hospital stay, recovery time and surgery-related pain. Patient management is
      facilitated by cystostomy.

PMID- 12068757
TI  - [PCNA and Ki-67 expression in locally confined renal adenocarcinoma. Relationship
      with various histopathologic variables and prognostic significance].
AB  - OBJECTIVE: PCNA and Ki-67 expression are used as markers of cellular
      proliferation and different studies have investigated their value as prognostic
      indicators for renal adenocarcinoma. The aim of this study was to determine PCNA
      and Ki-67 expression in locally confined renal adenocarcinoma, their relationship
      with other histopathological variables and prognostic significance. METHODS: 58
      cases of renal adenocarcinoma stages pT1-T3a N0 M0 (TNM 1997), treated by
      curative radical or partial nephrectomy were reviewed. The clinical and
      histopathological variables were analyzed. PCNA and Ki-67 expression in tissue
      embedded in paraffin were studied by immunohistochemical techniques. RESULTS: The
      mean percentage of nuclei that stained for PCNA was 7.03% (range 0-50%). Analysis
      of the correlation between PCNA and histopathological variables (size, grade and
      stage), showed a statistically significant correlation of PCNA only for the
      nuclear grade (p = 0.009). The mean percentage of nuclei that stained for Ki-67
      expression was 2.96% (range 0-30%) and a relationship was found for size (p <
      0.001), nuclear grade (p < 0.001) and stage (p < 0.001). The incidental clinical
      presentation, tumor size, stage, nuclear grade, PCNA and Ki-67 expression showed
      a relationship with survival. However, only perirenal fat infiltration, tumor
      size, nuclear grade and PCNA expression were found to be independent factors by
      multivariate analysis. CONCLUSIONS: PCNA expression correlated with nuclear
      grade, while Ki-67 demonstrated a significant correlation with tumor size, grade
      and stage. Survival analysis showed a relationship of both markers with
      prognosis. However, only PCNA was found to be an independent factor by
      multivariate analysis.

PMID- 12068759
TI  - [Collecting duct carcinoma. Personal experience and review of the literature].
AB  - OBJECTIVE: To present our experience with renal collecting duct carcinoma and
      review the literature. METHODS: We reviewed our experience with collecting duct
      carcinoma of the kidney. We found 6 cases out of 176 nephrectomies (3.4%), which
      accounts for one of the largest series reported in the literature. The
      radiological, histological and immunohistochemical findings are analyzed.
      RESULTS: The histological and immunohistochemical findings showed a specificity
      for high molecular weight cytokeratins and Ulex europeaeus but the imaging
      findings were not distinct from those of other renal tumors. According to the
      anatomopathological findings, we have classified the patients into three groups
      with three distinct courses. All patients underwent radical nephrectomy and one
      patient received adjuvant therapy. CONCLUSIONS: We have identified a subgroup of
      low grade collecting duct carcinoma of the kidney with a particularly favorable
      behavior in two patients of our series. At 56 and 41 months' follow-up, both
      patients remain disease-free. As reported in the literature, patients with high
      grade and stage collecting duct carcinoma of the kidney have a poor outcome. They
      develop severe complications and die less than one year after the diagnosis,
      despite adjuvant immunotherapy.

PMID- 12068758
TI  - [Lymphoma and kidney: report of 5 cases].
AB  - OBJECTIVE: To describe 5 cases of renal lymphoma. METHODS/RESULTS: A
      retrospective study was conducted on 5 cases of renal lymphoma that had been
      diagnosed at our institution in 1999. Of these 5 cases, one was considered to be
      primary renal lymphoma. The characteristics, treatment and outcome are discussed.
      CONCLUSIONS: Secondary kidney involvement from systemic lymphoma is common, but
      primary renal lymphoma is a rare and controversial entity.

PMID- 12068760
TI  - [Urachal diverticuli. Diagnosis and treatment].
AB  - OBJECTIVE: To determine the utility of different diagnostic imaging techniques in
      diverticulum of the urachus and discuss the approach in the incidentally
      discovered cases such as those detected due to infectious complications.
      METHODS/RESULTS: We reviewed the literature, with special reference to the
      diagnostic and therapeutic aspects of diverticula of the urachus. A case that
      presented with urinary infection and omphalitis, with the characteristic
      radiological findings, that resolved after surgical treatment and previous
      antibiotic therapy, is also described. CONCLUSIONS: Ultrasound is useful in the
      initial evaluation of patients with signs of periumbilical inflammation. If a
      urachal diverticulum is diagnosed, retrograde cystourethrography should be
      performed to rule out associated genitourinary pathology or lower urinary tract
      obstruction. In cases discovered incidentally, we underscore the importance of
      elective surgery to excise the diverticulum since it could progress to
      malignancy. In cases with infectious complications, bladder catheterization and
      antibiotic treatment before performing subsequent elective surgery offer
      advantages over primary excision. For young patients, we advocate performing the
      Pfannenstiel incision. This approach offers excellent visualization and exposure
      of the entire urachus with a minimum surgical scar.

PMID- 12068761
TI  - [Involvement of bladder neck and periurethral sphincter in dyssynergia in
      patients with spinal cord injury].
AB  - OBJECTIVE: To determine the degree of association of detrusor-periurethral
      dyssynergia and detrusor-bladder neck dyssynergia and if the voiding periurethral
      electromyographic (EMG) activity is also a valid method for diagnosing detrusor
      bladder neck dyssynergia. METHODS: A clinical, videourodynamic and selective
      periurethral EMG study was performed in 24 patients (mean age 33 years) with
      spinal cord injury and hyperreflexia of the bladder. RESULTS: The prevalence of
      bladder neck dyssynergia was 12.5% (3 cases) in this series. All patients with
      dyssynergic bladder neck also showed intermittent or sustained periurethral
      sphincter EMG activity. However, 15 patients showed increased intermittent or
      sustained voiding periurethral EMG activity that was not associated with detrusor
      bladder neck dyssynergia. Utilizing the videourodynamic demonstration of detrusor
      bladder neck dyssynergia as reference, selective periurethral EMG showed a
      sensitivity of 100% and a specificity of 29% for the diagnosis of detrusor
      bladder neck dyssynergia. CONCLUSIONS: The finding of bladder neck dyssynergia
      indicates the existence of detrusor-periurethral dyssynergia. However, not all
      cases of detrusor-periurethral sphincter dyssynergia is associated with bladder
      neck dyssynergia; therefore a videourodynamic study should be performed to rule
      out bladder neck dyssynergia in those patients with detrusor-periurethral
      sphincter dyssynergia. This is important in making the differential diagnosis and
      also has significant therapeutic repercussions.

PMID- 12068762
TI  - [Methylene blue: an effective therapeutic alternative for priapism induced by
      intracavernous injection of vasoactive agents].
AB  - OBJECTIVE: Priapism is defined as prolonged and persistent erection of the penis
      without sexual stimulation. Etiologies of this condition are numerous. Recent
      advances in the understanding of erectile physiology have improved the prompt
      diagnosis and treatment of priapism. Treatment of priapism varies from a
      conservative medical to a drastic surgical approach. Normally, priapism is
      effectively treated with intracavernous vasoconstrictive agents or surgical
      shunting. Recent findings indicate methylene blue (MB), a guanylate cyclase
      inhibitor, to be a potential inhibitor of endothelial-mediated cavernous
      relaxation. This prompted us to assess the feasibility, the use and the
      effectiveness of MB in the treatment of priapism. METHODS: 25 patients were
      treated for priapism. Etiologies were: 22 drug-mediated (PGE1 or
      papaverine/phentolamine mixture) after corpus cavernosum injection therapy
      (CCIT), 1 leukemia-induced and 2 idiopathic high-flow priapism. Patient ages
      ranged from 13 to 72 years. The average duration of priapism was 5 hours and 22
      minutes after CCIT. MB was administered after blood aspiration of the corpora
      cavernosa. 5 ml of MB was injected intracavernously (i.c.) and left for 5 min. MB
      was then aspirated and the penis compressed for an additional 5 min. RESULTS: All
      patients with CCIT-induced priapism were cured with MB alone. The 3 patients who
      did not respond to MB underwent i.c. phenylephrine administration and finally, if
      necessary, embolization of the pudendal artery. Etiology and duration of priapism
      were the strongest predictors for success with intracavernously administered MB.
      The primary side effects were a transient burning sensation and blue
      discoloration of the penis on injection of MB. The initial baseline erectile
      status was restored in all patients cured by MB. CONCLUSIONS: These results
      confirm that MB is a safe and highly effective treatment agent for short-term
      pharmacologically-induced priapism. Furthermore, MB demonstrates distinct
      advantages over a-adrenergic agents for intracavernous use, such as lower costs,
      absence of systemic or local toxic side effects and shorter treatment time
      leading to faster detumescence. For this reason, MB is a suitable and safe
      substance for alternative routine intracavernous therapy in males with
      pharmacologically-induced priapism.

PMID- 12068763
TI  - [Testicular necrosis caused by Fournier's gangrene: an exceptional case].
AB  - OBJECTIVE: To report an uncommon case of Fournier's gangrene caused by a
      perforated retrocecal acute appendicitis that compromised the scrotum and testis.
      METHODS: Herein we describe a patient that was admitted for abdominal pain
      localized to the right lower flank and generalized virulent sepsis. RESULTS:
      Resection of the right inguinal cord and testis was performed. The outcome was
      poor and the patient died of multiorgan failure. CONCLUSIONS: Fournier's gangrene
      basically arises from anorectal and urological pathologies, although occasionally
      it may arise from an intraabdominal source, which should be ruled out especially
      when the abdominal examination shows interesting findings.

PMID- 12068764
TI  - [Paratesticular leiomyosarcoma: report of a new case].
AB  - OBJECTIVE: To report an additional case of paratesticular leiomyosarcoma.
      METHODS: Herein we describe a 68-year-old male patient that presented with a
      growing, indolent, right inguinoscrotal lesion that he had noted several weeks
      earlier. Physical examination showed a mass involving the distal right spermatic
      cord and was confirmed by ultrasound and CT. Analyses were normal. Radical
      orchidectomy with high ligation of the right spermatic cord was performed.
      RESULTS: Histopathological and immunohistochemical studies demonstrated a well
      differentiated paratesticular leiomyosarcoma. Local recurrence was observed at 3
      1/2 years' follow-up. Complete excision of the tumorous tissue was performed with
      no other adjuvant therapy. Six months thereafter, there is no evidence of local
      recurrence or distant metastasis. CONCLUSIONS: This tumor type is uncommon. Like
      other authors, we believe that orchifuniculectomy is the treatment of choice.
      Furthermore, adjuvant radio or chemotherapy does not significantly influence
      survival in these patients.

PMID- 12068765
TI  - [Neuroblastoma in adolescence. Report of a new case].
AB  - OBJECTIVE: To report an uncommon case of neuroblastoma in adolescence. METHODS: A
      case of neuroblastoma in adolescence is presented. The etiological and
      pathogenetic factors, clinical and laboratory findings, behavior and treatments
      are discussed. RESULTS/CONCLUSIONS: Neuroblastoma and related tumors,
      ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest
      cells that migrate in the embrionary period and populate the primordial
      sympathetic ganglia and adrenal medulla. Neuroblastoma, the least differentiated,
      resembles the fetal adrenal medulla. The peak age at the time of presentation is
      about 18 months and only sporadic cases occur during adolescence, as the case
      described herein, or adult life.

PMID- 12068766
TI  - [Acute hematuria as first manifestation of bladder urothelioma in a 17-year-old
      adolescent].
AB  - OBJECTIVE: To report a case of urothelial tumor of the bladder in a 17-year-old
      patient that required emergency surgical treatment due to acute hematuria.
      METHODS: The clinical history, anatomopathological and immunohistochemical
      findings are described. RESULTS: A 17-year-old patient with no remarkable
      clinical history, consulted at the emergency services for gross hematuria of
      sudden onset that caused anemia and was refractory to conservative management.
      Patient evaluation disclosed a bladder lesion that required immediate resection
      via the transurethral approach to control bleeding. The pathological analysis
      demonstrated a grade I, Jewett stage 0, pTaN0M0 transitional cell carcinoma of
      the bladder. CONCLUSIONS: Urothelial tumors of the bladder are uncommon in
      patients less than 40 years old. The case described herein is uncommon because of
      the patient's age and the form of presentation of the tumor, which required
      emergency surgical treatment. Follow-up and subsequent therapy should be based on
      the pathological characteristics of the tumor rather the age of the patient.

PMID- 12068767
TI  - [Priapism secondary to chronic myeloid leukemia: value of initial treatment with
      cavernous lavage plus adjuvant methoxamine].
AB  - OBJECTIVE: To report a case of priapism secondary to leukemia, with special
      reference to the initial treatment in the emergency services. METHODS: A 53-year
      old male with chronic myeloid leukemia presented with prolonged involuntary
      painful erection of 12 hours' duration. The physical examination and particularly
      the cavernosal blood gas study, indicated low flow priapism. Punction-lavage of
      the corpora cavernosa was performed. Because complete response was not achieved
      with this procedure, adjuvant intracavernous methoxamine was administered.
      RESULTS: Complete detumescence was achieved after the third dose of methoxamine.
      There was no recurrence and erectile function was preserved. CONCLUSIONS: We
      underscore the utility of combined cavernous lavage + adjuvant alpha-1 adrenergic
      agonist as initial therapy in priapism with this special etiology.

PMID- 12068768
TI  - [Syringocele of the Cowper's gland. Report of 2 cases diagnosed in adulthood].
AB  - OBJECTIVE: To describe two cases of symptomatic syringocele diagnosed in adult
      patients. METHODS/RESULTS: Two cases of symptomatic syringocele diagnosed in
      adult patients that both consulted for obstructive voiding syndrome, are
      described. Diagnosis was made by retrograde urethrography. An incision extending
      to the outlet of the syringocele was performed in both cases. Good results were
      achieved and the symptoms remitted. CONCLUSIONS: Syringocele is the cystic
      dilatation of Cowper's gland. It is generally congenital and a majority of the
      symptomatic cases (urinary infection, obstruction or hematuria) are diagnosed in
      childhood. The diagnosis is based on the findings of retrograde urethrography and
      urethroscopy. Treatment is by urethroscopic incision or marsupialization of the
      syringocele. Some cases may require open surgery via the perineal approach.

PMID- 12068769
TI  - [Testicular epidermoid cyst. Report of 2 clinical cases and review of the
      literature].
AB  - OBJECTIVE: To report two cases of epidermoid cyst of the testis, with special
      reference to the diagnostic and therapeutic aspects, and to review the
      literature. METHODS: Two cases of epidermoid cyst of the testis are presented:
      one patient consulted for testicular swelling and the other for supraclavicular
      lymphadenopathy. RESULTS: In both cases the pathological diagnosis was testicular
      epidermoid cyst. CONCLUSIONS: Testicular epidermoid cysts are uncommon. High
      frequency ultrasonography is a reliable diagnostic imaging method. Treatment by
      tumor enucleation with preservation of the testis is advocated, when possible.

PMID- 12068770
TI  - Ureterolithotripsy in the management of calcified double-J catheter.
AB  - OBJECTIVE: The authors present their experience in the management of a rare
      complication observed during long-term use of a ureteral catheter. The
      calcification along the entire surface of the catheter followed by incrustation
      can make its removal by means of cystoscopy difficult, thus becoming a great
      challenge to the urologist. METHODS: The authors describe their experience in the
      management of this complication through the analysis of two illustrative cases.
      RESULTS: After failing to remove the catheter using extracorporeal lithotripsy,
      ureterolithotripsy was performed and the calcified ureteral catheter was
      successfully removed in both cases. CONCLUSION: Ureterolithotripsy proved to be
      an effective and safe method in the management of calcified double-J catheter.

PMID- 12068771
TI  - [Proceedings of the V National Conference on Obstetrics. Bansko, Bulgaria,
      February, 2001].

PMID- 12068772
TI  - The current most pressing concerns of implant dentistry.

PMID- 12068773
TI  - Wider horizons.

PMID- 12068774
TI  - Make IT work for you.

PMID- 12068775
TI  - Get clicking. You've got m@il...

PMID- 12068776
TI  - Bringing research closer to you.

PMID- 12068777
TI  - Fundamental notes.

PMID- 12068778
TI  - Stolen moments.

PMID- 12068779
TI  - Sisteract.

PMID- 12068780
TI  - A byte of lunch.

PMID- 12068781
TI  - Log on to a worldwide link.

PMID- 12068782
TI  - Global practice.

PMID- 12068783
TI  - Welcome to wicker's world.

PMID- 12068784
TI  - A method for estimating torque-vector directions of shoulder muscles using
      surface EMGs.
AB  - In this study, a new method is proposed to estimate the torque-vector directions
      of each shoulder muscle. The method is based on a multiple regression model that
      reconstructs shoulder torque, which is calculated from the hand force and
      posture, from the surface EMG of many muscles recorded simultaneously. The torque
      vector directions of eleven shoulder muscles of four subjects were obtained at up
      to 30 different arm postures with this method. The mean confidence interval (p <
      0.05) of the estimated torque-vector direction of each subject was 7.7-10.6
      degrees. The correlation coefficient between the measured shoulder torque and
      reconstructed shoulder torque was between 0.76-0.84. The results for majority of
      the muscles were in accordance with previous studies, and reasonable from the
      viewpoint of anatomy. The torque-vector directions of a muscle, which are
      estimated with this method, have more of a functional meaning than a pure
      anatomical or mechanical one. These indicate the direction of the shoulder torque
      accompanying the muscle activation for a normal shoulder action that involves the
      cooperative contraction of many muscles.

PMID- 12068785
TI  - Decoding of a motor command vector from distributed activity in superior
      colliculus.
AB  - Several alternative methods for decoding the desired motor command vector from
      neural networks containing distributed, place-coded information have been
      suggested. The two most widely discussed candidate mechanisms are vector
      summation (VS) and a center-of-mass (CM) computation. The latter mechanism has
      also been called vector averaging. The present paper compares the operation of
      these two methods in a model of an experimentally well-studied neural structure,
      the superior colliculus (SC). The SC is one structure that has been shown to be
      responsible for generating saccadic command vectors in the form of distributed
      neural activity that is topologically arranged across its surface. It has been
      suggested that the pattern of eye-movement errors obtained following the
      placement of a collicular lesion can distinguish between these two mechanisms. As
      a result of this suggestion, the pattern of saccadic errors produced by lesions
      in the SC have been widely cited to support the CM hypothesis. In the present
      paper the placement of a discrete lesion is simulated in a recurrent (dynamic)
      neural network model of the SC. These dynamic connections in the model SC network
      produce a systematic shift of the locus of distributed activity away from the
      site of the lesion. The spatiotemporal shift in the location of SC activity then
      produces a pattern of saccadic errors that appear to support the CM hypothesis,
      even though ensemble activity in our model colliculus is decoded by VS. This
      result demonstrates that, when ensemble activity on the SC motor map is
      dynamically modulated over space and time by intrinsic collicular circuitry, an
      explicit CM computation is not needed to reproduce the pattern of physiological
      results that follow focal SC lesions.

PMID- 12068786
TI  - Theoretical considerations on canal-otolith interaction and an observer model.
AB  - Subjective vertical orientation, eye and body movements, and motion sickness all
      depend on the way our central nervous system deals with the gravito-inertial
      force resolution problem: how to discern accelerations due to motion from those
      due to gravity, despite these accelerations being physically indistinguishable.
      To control body or eye movements, the accelerations due to motion should be known
      explicitly. Hence, somehow gravity should be filtered out of the specific force
      or gravito-inertial acceleration (GIA, the sum of both accelerations) as sensed
      by the otoliths, which are the linear accelerometers in the inner ear. As the GIA
      also changes in a head-fixed frame of reference when the head is rotated, angular
      motion as sensed by the semicircular canals in the inner ear should also be
      considered. We present here a theoretical approach to this problem, and show that
      the mathematical description of canal-otolith interaction is in fact a three
      dimensional equivalent of the two-dimensional description given by Mayne in 1974.
      A simple low-pass filter is used to divide the GIA into a motion and a gravity
      component. The retardation of the somatogravic effect by concomitant angular
      motion during centrifugation is shown as a result. Furthermore we show how the
      canal-otolith interaction fits within the framework of an observer model to
      describe subjective vertical orientation, eye movement and motion sickness
      characteristics. To predict a frequency peak in sickness severity, for example,
      it is necessary to explicitly include the Mayne equation operating both on sensor
      afferents and in the internal model. From tilt and translation data from
      centrifugation and horizontal oscillation, as well as from motion sickness data,
      we conclude that the time constant of the low-pass filter is in the order of
      seconds instead of tens of seconds as assumed before. Several corollaries are
      additionally discussed as a result.

PMID- 12068787
TI  - Using sensory weighting to model the influence of canal, otolith and visual cues
      on spatial orientation and eye movements.
AB  - The sensory weighting model is a general model of sensory integration that
      consists of three processing layers. First, each sensor provides the central
      nervous system (CNS) with information regarding a specific physical variable. Due
      to sensor dynamics, this measure is only reliable for the frequency range over
      which the sensor is accurate. Therefore, we hypothesize that the CNS improves on
      the reliability of the individual sensor outside this frequency range by using
      information from other sensors, a process referred to as "frequency completion."
      Frequency completion uses internal models of sensory dynamics. This "improved"
      sensory signal is designated as the "sensory estimate" of the physical variable.
      Second, before being combined, information with different physical meanings is
      first transformed into a common representation; sensory estimates are converted
      to intermediate estimates. This conversion uses internal models of body dynamics
      and physical relationships. Third, several sensory systems may provide
      information about the same physical variable (e.g., semicircular canals and
      vision both measure self-rotation). Therefore, we hypothesize that the "central
      estimate" of a physical variable is computed as a weighted sum of all available
      intermediate estimates of this physical variable, a process referred to as
      "multicue weighted averaging." The resulting central estimate is fed back to the
      first two layers. The sensory weighting model is applied to three-dimensional
      (3D) visual-vestibular interactions and their associated eye movements and
      perceptual responses. The model inputs are 3D angular and translational stimuli.
      The sensory inputs are the 3D sensory signals coming from the semicircular
      canals, otolith organs, and the visual system. The angular and translational
      components of visual movement are assumed to be available as separate stimuli
      measured by the visual system using retinal slip and image deformation. In
      addition, both tonic ("regular") and phasic ("irregular") otolithic afferents are
      implemented. Whereas neither tonic nor phasic otolithic afferents distinguish
      gravity from linear acceleration, the model uses tonic afferents to estimate
      gravity and phasic afferents to estimate linear acceleration. The model outputs
      are the internal estimates of physical motion variables and 3D slow-phase eye
      movements. The model also includes a smooth pursuit module. The model matches eye
      responses and perceptual effects measured during various motion paradigms in
      darkness (e.g., centered and eccentric yaw rotation about an earth-vertical axis,
      yaw rotation about an earth-horizontal axis) and with visual cues (e.g.,
      stabilized visual stimulation or optokinetic stimulation).

PMID- 12068788
TI  - A neural network model of the inferior colliculus with modifiable lateral
      inhibitory synapses for human echolocation.
AB  - We propose a neural network model of the inferior colliculus (IC) for human
      echolocation. Neuronal mechanisms for human echolocation were investigated by
      simulating the model. The model consists of the neural networks of the central
      nucleus (ICc) and external nucleus (ICx) of the inferior colliculus. The neurons
      of the ICc receive interaural sound stimuli via multiple contralateral delay
      lines and a single ipsilateral delay line. The neurons of the ICc send output
      signals to the neurons of the ICx in a convergent manner. We stimulated the ICc
      with pairs of a direct sound (a sonar sound) and an echo sound (the reflection
      from an object). Information about the distance between the model and the object
      is expressed by the delay time of the echo sound with respect to the direct
      sound. The results presented here show that neurons of the ICc responsive to
      interaural onset time differences contribute to the creation of an auditory
      distance map in the ICx. We trained the model with various pairs of direct-echo
      sounds and modified synaptic connection strengths of the networks according to
      the Hebbian rule. It is shown that self-organized long-term depression of lateral
      inhibitory synaptic connections plays an important role in enhancing echolocation
      skills.

PMID- 12068789
TI  - Quantifying the strength of the linear causal coupling in closed loop interacting
      cardiovascular variability signals.
AB  - The coherence function measures the amount of correlation between two signals x
      and y as a function of the frequency, independently of their causal
      relationships. Therefore, the coherence function is not useful in deciding
      whether an open-loop relationship between x and y is set (x acts on y, but the
      reverse relationship is prevented) or x and y interact in a closed loop (x
      affects y, and vice versa). This study proposes a method based on a bivariate
      autoregressive model to derive the strength of the causal coupling on both arms
      of a closed loop. The method exploits the definition of causal coherence. After
      the closed-loop identification of the model coefficients, the causal coherence is
      calculated by switching off separately the feedback or the feedforward path, thus
      opening the closed loop and fixing causality. The method was tested in
      simulations and applied to evaluate the degree of the causal coupling between two
      variables known to interact in a closed loop mainly at a low frequency (LF,
      around 0.1 Hz) and at a high frequency (HF, at the respiratory rate): the heart
      period (RR interval) and systolic arterial pressure (SAP). In dogs at control,
      the RR interval and the SAP are highly correlated at HF. This coupling occurs in
      the causal direction from the RR interval to the SAP (the mechanical path), while
      the coupling on the reverse causal direction (the baroreflex path) is not
      significant, thus pointing out the importance of the direct effects of
      respiration on the RR interval. Total baroreceptive denervation, by opening the
      closed loop at the level of the influences of SAP on RR interval, does not change
      these results. In elderly healthy men at rest, the RR interval and SAP are highly
      correlated at the LF and the HF. At the HF, a significant coupling in both causal
      directions is found, even though closed-loop interactions are detected in few
      cases. At the LF, the link on the baroreflex pathway is negligible with respect
      to that on the reverse mechanical one. In heart transplant recipients, in which
      SAP variations do not cause RR interval changes as a result of the cardiac
      denervation, the method correctly detects a significant coupling only on the
      pathway from the RR interval to the SAP.

PMID- 12068791
TI  - [Code Guide: Paediatric and adolescent medicine of the DRG Working Group
      comprising all other associations].

PMID- 12068790
TI  - [Human microsporidiosis].

PMID- 12068792
TI  - Cell surface expression of CD25, CD54, and CD95 on B- and T-cells in chronic
      lymphocytic leukaemia in relation to trisomy 12, atypical morphology and clinical
      course.
AB  - BACKGROUND: Surface antigen expression can be used to define subgroups of
      patients with different clinical courses in chronic lymphocytic leukaemia of the
      B-cell type (CLL). PURPOSE-METHODS: To study the clinical significance of
      functional markers linked to proliferation (CD25), adhesion (CD54), and apoptosis
      (CD95) on B- and T-cells in 68 patients with CLL using dual colour flow cytometry
      (FCM). RESULTS: The mean proportion of CD19+ B-cells expressing CD25 was
      significantly higher in CLL patients compared to controls (P=0.02), while CD54+
      and CD95+ B-cells did not differ significantly. In CLL with atypical morphology
      and in patients with trisomy 12, the mean percentage of CD25+ B-cells was lower
      than in typical CLL (P<0.02) and in patients with disomic tumor cells (P<0.03).
      Patients with 30% of CD25+ B-cells had a shorter median time to treatment than
      CD25-negative cases (P=0.01). A low CD54 expression was associated with a
      prolonged median time to treatment (P=0.004), low WBC counts (P<0.05), and low S
      LDH (P=0.03). A high CD95 expression was correlated with elevated S-LDH (P=0.02)
      and a finding of lymphadenopathy (P=0.02). In individual patients there was a
      strong correlation between B- and T-cell expression of CD25 (P<0.0001), CD54
      (P=0.0002), and CD95 (P=0.0002), respectively. CONCLUSIONS: CD25 and CD54
      expression on CD19+ cells seems to give prognostic information. The strong
      correlation between the expression of CD25, CD54 and CD95 on B-and T-cells
      suggests that the expression of these antigens is not an inherent characteristic
      of the malignant B-cell clone.

PMID- 12068793
TI  - Treatment of intermediate- and high-grade non-Hodgkin's lymphoma using CEOP
      versus CNOP.
AB  - INTRODUCTION: During the last few years epirubicin (E) and mitoxantrone (M)
      (Novantrone) have been used in the treatment of non-Hodgkin's lymphoma (NHL),
      because of their favorable principal profile. In particular, M has less severe
      non-hematological toxicity. PATIENTS AND METHODS: A randomized multicenter phase
      III study was conducted in order to compare the efficacy and toxicity of CEOP and
      CNOP in intermediate- and high-grade NHL. CEOP (arm A) consisted of
      cyclophosphamide 1000mg m(-2), vincristine 2mg, E 70mg m(-2) on day 1 and
      prednisone 60mg on days 1-7. The CNOP regimen (arm B) was identical to CEOP
      except for replacement of E by M at a dose of 12mg m(-2). Randomization was
      stratified according to stages I-IV. From September 1993 to March 1999, 249
      patients registered for the trial. Patient characteristics were equally
      distributed in the two arms, except for age and International Prognostic Index
      (IPI) groups. RESULTS: There were no significant differences between the two
      groups in the rates of complete (CR) and partial response (PR). The overall
      response rate was 78% in arm A (57% CR, 21% PR) and 82% in arm B (60% CR, 22%
      PR). With a median follow-up time of 47.3 months, the median survival was not
      reached in arm A, while it was 39.5 months in arm B (P=0.09). Three-year survival
      rates were 62.5% for CEOP and 51.5% for CNOP. There was no significant difference
      regarding the time to progression between the two groups (29.7 vs. 18.5 months);
      furthermore the median duration of CRs was 71.6 and 49 months for CEOP and CNOP,
      respectively (P=0.07). The therapeutic efficacies of both regimens were
      equivalent among the four IPI groups. More alopecia was observed in arm A. WHO
      grade >2 neutropenia was more frequent in arm B. Supportive treatment with G-CSF
      was given to 22 and 24 patients, respectively. CONCLUSION: There were no
      significant differences in terms of overall response rates, overall survival and
      time to progression between CEOP and CNOP in the treatment of intermediate- and
      high-grade NHL. Patients with low or low intermediate IPI risk treated with
      either CEOP or CNOP showed significantly better survival, response rates and time
      to progression than those with high intermediate or high IPI risk. Therefore, new
      improved therapeutic approaches should be developed for the treatment of high IPI
      risk patients.

PMID- 12068794
TI  - Combined therapy in advanced stages (III and IV) of follicular lymphoma increases
      the possibility of cure: results of a large controlled clinical trial.
AB  - OBJECTIVES: We evaluate the long-term results of a randomized clinical trial in
      patients with advanced stages (III and IV) of follicular lymphoma using
      chemotherapy or combined therapy (chemotherapy following by adjuvant radiotherapy
      in patients with nodal bulky disease). MATERIAL AND METHODS: Between 1981 and
      1995, patients with follicular lymphoma were treated with combined chemotherapy,
      mostly anthracycline-based regimens; patients who achieved complete response were
      randomly assigned either to receive adjuvant radiotherapy to sites or to nodal
      bulky disease or not (control group). RESULTS: Four hundred and sixty-nine
      patients were randomized; in an intent-to-treat analysis all were evaluable for
      efficacy and toxicity. Actuarial curves at 20yr showed that event-free survival
      (EFS) and overall survival (OS) in the control group were 41% [95% confidence
      interval (CI) 36-56%) and 71% (95% CI 65-78%), respectively; these were
      statistically different from results for the patients who received adjuvant
      radiotherapy: 68% (95% CI 62-72%) and 89% (95% CI 79-96%), respectively (P<0.01).
      Acute and late toxicity were minimal; only four patients (<1%) developed
      myelodysplastic syndrome/acute leukemia. Cardiac toxicity was 2%, but one case
      was lethal. Thirty-six patients (8%) died secondary to unrelated causes, in
      complete remission. CONCLUSIONS: The use of adjuvant radiotherapy in patients
      with poor-prognosis follicular lymphoma increases EFS and OS with minimal
      toxicity. We feel that follicular lymphoma should be treated curatively because
      <80% of patients will be in first complete response at <20yr. The use of adjuvant
      radiotherapy will be considered in the first line of treatment in this set of
      patients.

PMID- 12068795
TI  - The Advia 120 red blood cells and reticulocyte indices are useful in diagnosis of
      iron-deficiency anemia.
AB  - We have investigated the red blood cell (RBC) and reticulocyte indices of the
      Advia 120 hematology system in assessment of body iron stores as well as in
      diagnostics of iron-deficiency anemia in two separate study populations. The
      first study population consisted of a total of 34 apparently healthy females who
      were found to be anemic (Hb<125gL1) in a screening test. The anemic subjects were
      classified on the basis of plasma transferrin receptor (TfR) concentration into
      an iron-deficiency anemia group (TfR concentration 2.4mgL1, n=14) and an adequate
      iron stores group (TfR concentration <2.4mgL1, n=20). Another study population
      consisted of 95 hospital patients of whom 31 had depleted iron stores according
      to TfR concentration. The same population was classified further on the basis of
      hemoglobin value (Hb<125gL1 for females, Hb<135gL1 for males) into patients with
      iron-deficiency anemia (n=21) and those with anemia together with adequate iron
      stores (n=44). In the population of young anemic female students the percentage
      of hypochromic RBC (%HYPOm) had a remarkably high ROC AUC of 0.98 when evaluating
      the diagnostic accuracy for the distinction between the patients with iron
      deficiency anemia and those with anemia and adequate iron stores. Also, among the
      hospitalized patients %HYPOm had the highest ROC AUC of 0.77. The diagnostic
      efficiency provided by the red blood cell and reticulocyte indices was
      considerably lower in the heterogeneous group of hospitalized patients than in
      the group of female students. Nevertheless, the advanced RBC and reticulocyte
      indices may prove to be useful tools in the evaluation of iron status and
      diagnosis of iron-deficiency anemia.

PMID- 12068796
TI  - The comprehensiveness care of sickle cell disease.
AB  - Millions of people across the world have sickle cell disease (SCD). Although the
      true prevalence of SCD in Europe is not certain, London (UK) alone had an
      estimated 9000 people with the disorder in 1997. People affected by SCD are best
      managed by a multidisciplinary team of professionals who deliver comprehensive
      care: a model of healthcare based on interaction of medical and non-medical
      services with the affected persons. The components of comprehensive care include
      patient/parent information, genetic counselling, social services, prevention of
      infections, dietary advice and supplementation, psychotherapy, renal and other
      specialist medical care, maternal and child health, orthopaedic and general
      surgery, pain control, physiotherapy, dental and eye care, drug dependency
      services and specialist sickle cell nursing. The traditional role of
      haematologists remains to co-ordinate overall management and liase with other
      specialities as necessary. Co-operation from the affected persons is
      indispensable to the delivery of comprehensive care. Working in partnership with
      the hospital or community health service administration and voluntary agencies
      enhances the success of the multidisciplinary team. Holistic care improves the
      quality of life of people affected by SCD, and reduces the number as well as
      length of hospital admissions. Disease-related morbidity is reduced by early
      detection and treatment of chronic complications. Comprehensive care promotes
      awareness of SCD among affected persons who are encouraged to take greater
      control of their own lives, and achieves better patient management than the solo
      efforts of any single group of professionals. This cost-effective model of care
      is an option for taking haemoglobinopathy services forward in the new millennium.

PMID- 12068797
TI  - Sickle erythrocytes increase prostacyclin and endothelin-1 production by cultured
      human endothelial cells under flow conditions.
AB  - We investigated the effects of sickle erythrocytes on the production of vasotone
      mediators in endothelial cells (ECs) using an in vitro recirculating flow system.
      Sickle erythrocytes increased the EC production of two important vasoactivators,
      prostacyclin and endothelin-1, under venous wall shear stress conditions of
      1dyncm2. The presence of interleukin-1 in the perfusion system, as a model for
      inflammatory cytokine effects, enhanced the overall amounts of released
      prostacyclin but did not affect the production of endothelin-1. This study
      demonstrates the effects of sickle erythrocytes on the function and metabolism of
      ECs under vascular flow environments. The altered production of vasoactivators
      may contribute to the vasotone instability and vasoocclusive crises in sickle
      cell anemia.

PMID- 12068798
TI  - Clinical and laboratory manifestations of congenital dyserythropoietic anemia
      type I in young adults.
AB  - OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I is a rare autosomal
      recessive macrocytic anemia whose natural history is not well documented. The aim
      of the present study was to evaluate the clinical picture of the disease in young
      adults. METHODS: The study sample consisted of 17 patients of mean age 11.9 +/-
      5.4 yr (range 18-33 yr) and one older patient (age 44 yr), all Israeli Bedouins.
      The degree of anemia was evaluated as well as the extent of development of
      gallstones and iron overload. In each subject we determined the hemochromatosis
      gene mutations and the uridine dyphosphate-glucoronosyltransferase (UGT-1A) gene
      polymorphism associated with Gilbert's syndrome. RESULTS: The patients were found
      to have moderate anemia, with the women displaying lower mean hemoglobin levels
      than the men (8.2 +/- 0.9 g dL(-1) vs. 10 +/- 1.3 g dL(-1); P=0.0059). The
      majority of patients (59%) had received at least one blood transfusion, with the
      women having a significantly higher transfusion requirement. Although delayed
      puberty was noted, final height and weight were within normal limits, and eight
      patients had progeny. Biliary stones were found in three of 16 patients, two of
      whom were homozygous for UGT-1A gene polymorphism. None of the patients carried
      the common hemochromatosis gene mutation, although serum ferritin levels were
      moderately elevated (788 +/- 332 ng mL(-1)). CONCLUSIONS: CDA type I in young
      adults is characterized by moderate macrocytic anemia, more severe in women, and
      a tendency to cholelithiasis and secondary progressive iron overload. We suggest
      that iron overload in this patient population should be monitored and chelation
      therapy initiated when indicated to prevent organ damage

PMID- 12068799
TI  - Simultaneous measurement of serum thrombopoietin and expression of megakaryocyte
      c-Mpl with clinical and laboratory correlates for myelofibrosis with myeloid
      metaplasia.
AB  - OBJECTIVES: We sought to investigate potential mechanisms of increased serum
      thrombopoietin (TPO) concentrations in myelofibrosis with myeloid metaplasia
      (MMM) by simultaneously measuring serum TPO, platelet and megakaryocyte (MK)
      numbers, and MK c-Mpl expression. METHODS: We studied 17 consecutive patients who
      had MMM and were not receiving therapy at the time of evaluation. Serum TPO was
      measured by a two-site immunochemiluminometric assay. Immunohistochemical
      staining of c-Mpl was accomplished with an immunoperoxidase method on
      simultaneously obtained bone marrow specimens. RESULTS: Our findings confirmed
      the presence of inappropriately increased serum TPO despite mostly normal or
      increased peripheral platelet counts and markedly increased bone marrow MK
      numbers. In addition, we found an inverse correlation between platelet count and
      serum TPO (P<0.03) and splenic size (P<0.04). However, serum TPO did not
      correlate with either bone marrow MK number or c-Mpl expression. The lack of
      correlation of serum TPO and bone marrow megakaryocyte number may be accounted
      for by the unavoidable inaccuracies in quantifying megakaryocytopoiesis in a
      disorder of known altered hematopoietic progenitor cell distribution, both
      intramedullary and extramedullary. The significant inverse correlation between
      serum TPO and spleen size suggests that this site of extramedullary
      megakaryocytopoiesis may assume a role in the dysfunctional TPO regulatory axis.
      CONCLUSIONS: These observations suggest some preservation of the negative
      feedback regulation that appears to be dysfunctional at the MK c-Mpl level.
      Consistent with previous observations in animal models, our observations suggest
      the possibility that altered TPO regulation resulting in sustained ligand excess
      may have pathogenetic relevance in MMM.

PMID- 12068800
TI  - Serum erythropoietin (EPO) levels correlate with survival and independently
      predict response to EPO treatment in patients with myelodysplastic syndromes.
AB  - Treatment with recombinant erythropoietin (EPO) can alleviate anaemia in patients
      with myelodysplastic syndromes (MDS). The present study, based on a long-term
      follow-up of 68 MDS patients (26RA, 16 RAS, 26 RAEB) treated with EPO alone,
      pinpoints pre-treatment variables associated with response induction, response
      duration and overall survival. Response, defined as an increase in haemoglobin
      >15gL1 or eliminated erythrocyte transfusion requirements, was observed in 22 of
      66 (33%) evaluable patients. The median response duration was 15 (range 3-64+)
      months. Using univariate logistic regression models, responders displayed
      significantly lower baseline serum EPO levels (S-EPO), more often normal bone
      marrow blast cell content (RA/RAS vs. RAEB), normal cytogenetics and no need for
      erythrocyte transfusion. In a multiple logistic regression model, S-EPO
      (P=0.009), marrow blast content (P=0.031) and erythrocyte transfusion need
      (P=0.024) remained associated with response induction. The probability of
      response for a patient with S-EPO >50UL1, RA/RAS and no transfusion need was 0.79
      (0.53-0.93, 95% CI). The median overall survival time from start of EPO treatment
      was 26 months, significantly longer for responders than for non-responders (49
      vs. 18 months, P=0.018). Survival was also predicted by baseline S-EPO; patients
      with S-EPO >50UL1 (n=50) had a median survival of 17 months, as compared to 65
      months for those with S-EPO >50UL1 (n=14, P=0.024). The international prognostic
      scoring system (IPSS) for MDS predicted survival (P=0.003) and progression to
      acute leukemia (P<0.001) but not response to EPO treatment. Furthermore, in a
      logistic regression model with S-EPO and IPSS, S-EPO (but not IPSS) was again a
      significant predictor for response (P=0.007). Our data facilitate the optimal
      selection of MDS patients suitable for EPO treatment and pinpoint S-EPO as a
      powerful predictor of response and overall survival in MDS.

PMID- 12068801
TI  - Mystery of multidrug transporters: the answer can be simple.
AB  - Multidrug efflux transporters, found in all living cells and protecting them from
      multiple structurally dissimilar hydrophobic toxins, have fascinated researchers
      for decades and presented a number of puzzling questions. These transporters
      demonstrate a remarkably broad substrate specificity, which seemingly contradicts
      established dogmas of biochemistry. Although sharing highly unusual properties,
      in some unexplained way, they have arisen multiple times in the evolution of
      several families of membrane proteins. Furthermore, the number of multidrug
      transporters encoded in each genome is so large that their role in cellular
      physiology has remained un-certain. Recent advances in the structural analysis of
      a number of soluble multidrug-recognizing proteins show that these proteins
      possess large hydrophobic binding sites and bind their substrates through a
      combination of a hydrophobic effect and electrostatic attraction, rather than by
      establishing a precise network of hydrogen bonds and other specific interactions
      characteristic of traditionally studied enzymes and receptors. Low-resolution
      structural studies of multidrug transporters suggest that they possess similar
      large binding sites and may use similar simple principles of substrate
      recognition. This would explain not only their broad substrate specificity, but
      also their unusual evolutionary relationships and the apparent multiplicity in
      genomes of organisms of all evolutionary kingdoms. Although further structural
      studies will be needed to prove this hypothesis, it is already clear that the
      explanation of the puzzling phenomenon of multidrug efflux may not necessarily
      require any substantially new biochemical or biological principles.

PMID- 12068802
TI  - An aspartate ring at the TolC tunnel entrance determines ion selectivity and
      presents a target for blocking by large cations.
AB  - The TolC protein of Escherichia coli comprises an outer membrane beta-barrel
      channel and a contiguous alpha-helical tunnel spanning the periplasm, providing
      an exit duct for protein export and multidrug efflux. It forms a single
      transmembrane pore that is open to the outside of the cell but constricted at the
      peri-plasmic tunnel entrance. This sole constriction is lined by a ring of six
      aspartate residues, two in each of the three identical monomers. When these were
      replaced by alanines, the resulting TolC(DADA) protein reconstituted normally in
      black lipid membranes but showed altered electrophysiological characteristics. In
      particular, it had lost the strong pH dependence of the wild type and had
      switched ion selectivity from cations to anions. The function of wild-type TolC
      as a membrane pore was severely inhibited by divalent and trivalent cations
      entering the channel tunnel from the channel ("extracurricular") side. Divalent
      cations bound reversibly to effect complete blocking of the transmembrane ion
      flux. Trivalent cations were more potent. Hexamminecobalt bound at nanomolar
      concentrations allowed visualization of single blocking events, whereas the
      smaller Cr(3+) cation bound irreversibly and could also access the cation binding
      site via the tunnel entrance. The inhibitory cations had no effect on the mutant
      TolC(DADA), supporting the view that the aspartate ring is the cation binding
      site. The electronegative entrance is widely conserved throughout the TolC
      family, which is essential for efflux and export my Gram-negative bacteria,
      suggesting that it could present a general target for drugs.

PMID- 12068803
TI  - A novel cyclic GMP-dependent protein kinase is expressed in the ring stage of the
      Plasmodium falciparum life cycle.
AB  - Cyclic GMP-dependent protein kinases (PKGs) are the major mediators of the cGMP
      signal transduction pathway and regulate a variety of physiological effects. We
      report here the characterization of an unusual PKG from the human malaria
      parasite Plasmodium falciparum (designated PfPKG). The 97.5 kDa protein contains
      some of the structural features of mammalian PKGs but, uniquely, contains a third
      predicted cGMP binding site and a degenerate fourth. Using both protein kinase
      activity assays and Western blotting with native P. falciparum proteins, we
      demonstrate here that PfPKG is expressed predominantly in the ring stage of the
      life cycle, suggesting a role in the development of asexual blood stage
      parasites. An Escherichia coli-derived recombinant protein (PfPKG2, Met115
      Phe853) was purified and shown to have phosphotransferase activity in terms of
      both substrate phosphorylation and auto-phosphorylation. This activity was
      stimulated at least fivefold by 1.0 microM cyclic GMP, but was not stimulated by
      cAMP or by 8-pCPT-cGMP, which is a potent activator of mammalian PKGs. Several
      protein kinase inhibitors exhibited a range of inhibitory effects on PfPKG
      activity. Biochemical analysis therefore shows that PfPKG is distinct from
      mammalian PKGs with respect to both cyclic nucleotide analogue activation and
      inhibition profiles.

PMID- 12068804
TI  - Rho1p mutations specific for regulation of beta(1-->3)glucan synthesis and the
      order of assembly of the yeast cell wall.
AB  - In the yeast Saccharomyces cerevisiae, the GTP-binding protein Rho1 is required
      for beta(1-->3)glucan synthase activity, for activation of protein kinase C and
      the cell integrity pathway and for progression in G1, cell polarization and
      exocytosis. A genetic screen for cells that become permeabilized at non
      permissive temperature was used to isolate in vitro-generated mutants of Rho1p.
      After undergoing a battery of tests, several of them appeared to be specifically
      defective in the beta(1-->3) glucan synthesis function of Rho1p. At the non
      permissive temperature (37 degrees C), the mutants developed defects in the cell
      wall, especially at the tip of new buds. In the yeast cell wall, beta(1-
      >6)glucan is linked to both beta(1-->3)glucan and mannoprotein, as well as
      occasionally to chitin. We have used the rho1 mutants to study the order of
      assembly of the cell wall components. The incorporation of [(14)C]-glucose into
      beta(1-->3)glucan at 37 degrees C was decreased or abolished in the mutants.
      Concomitantly, a partial defect in the incorporation of label into cell wall
      mannoproteins and beta(1-->6)glucan was observed. In contrast, YW3458, an
      inhibitor of glycosylphosphatidylinositol anchor formation, prevented
      mannoprotein incorporation, whereas the beta(1-->3)-beta(1-->6)glucan complex was
      synthesized at almost normal levels. As beta(1-->3)glucan can be synthesized in
      vitro or in vivo independently, we conclude that the order of addition in vivo is
      beta(1-->3)glucan, beta(1-->6)glucan, mannoprotein. Previous observations
      indicate that chitin is the last component to be incorporated into the complex.

PMID- 12068805
TI  - Characterization of Burkholderia pseudomallei infection and identification of
      novel virulence factors using a Caenorhabditis elegans host system.
AB  - The environmental saphrophyte Burkholderia pseudomallei is the causative agent of
      melioidosis, a systemic, potentially life-threatening condition endemic to many
      parts of south-east Asia and northern Australia. We have used the soil nematode
      Caenorhabditis elegans as a model host to characterize the mechanisms by which
      this bacterium mounts a successful infection. We find that C. elegans is
      susceptible to a broad range of Burkholderia species, and that the virulence
      mechanisms used by this pathogen to kill nematodes may be similar to those used
      to infect mammals. We also find that the specific dynamics of the C. elegans-B.
      pseudomallei host-pathogen interaction can be highly influenced by environmental
      factors, and that nematode killing results at least in part from the presence of
      a diffusible toxin. Finally, by screening for bacterial mutants attenuated in
      their ability to kill C. elegans, we genetically identify several new potential
      virulence factors in B. pseudomallei. The use of C. elegans as a model host
      should greatly facilitate future investigations into how B. pseudomallei can
      interact with host organisms.

PMID- 12068806
TI  - A signal transduction system in Streptomyces coelicolor that activates the
      expression of a putative cell wall glycan operon in response to vancomycin and
      other cell wall-specific antibiotics.
AB  - We have investigated a signal transduction system proposed to allow Streptomyces
      coelicolor to sense and respond to changes in the integrity of its cell envelope.
      The system consists of four proteins, encoded in an operon: sigmaE, an RNA
      polymerase factor; CseA (formerly ORF202), a protein of unknown function; CseB, a
      response regulator; and CseC, a sensor histidine protein kinase with two
      predicted transmembrane helices (Cse stands for control of sigma E). To develop a
      sensitive bioassay for inducers of the sigE system, the promoter of the sigE
      operon (sigEp) was fused to a reporter gene conferring resistance to kanamycin.
      Antibiotics that acted as inducers of the sigE signal transduction system were
      all inhibitors of intermediate and late steps in peptidoglycan biosynthesis,
      including ramoplanin, moenomycin A, bacitracin, several glycopeptides and some
      beta-lactams. The cell wall hydrolytic enzyme lysozyme also acted as an inducer.
      These data suggest that the CseB-CseC signal transduction system may be activated
      by the accumulation of an intermediate in peptidoglycan biosynthesis or
      degradationa. A computer-based searching method was used to identify a sigmaE
      target operon of 12 genes (the cwg operon), predicted to specify the biosynthesis
      of a cell wall glycan. In low-Mg(2+) medium, transcription of the cwg operon was
      induced by vancomycin in a sigE-dependent manner but, in high-Mg(2+) medium,
      there was substantial cwg transcription in a sigE null mutant, and this sigE
      independent activity was also induced by vancomycin. Based on these data, we
      propose a model for the regulation and function of the sigmaE signal transduction
      system.

PMID- 12068807
TI  - Export of the siderophore enterobactin in Escherichia coli: involvement of a 43
      kDa membrane exporter.
AB  - The enterobactin system for iron transport in Escherichia coli is well
      characterized with the exception of the mechanism of enterobactin secretion to
      the extracellular environment. Escherichia coli membrane protein P43, encoded by
      ybdA in the chromosomal region of genes involved in enterobactin synthesis, shows
      strong homology to the 12-transmembrane segment major facilitator superfamily of
      export pumps. A P43-null mutation was created and siderophore nutrition assays,
      performed with a panel of E. coli strains expressing one or more outer membrane
      receptors for enterobactin-related compounds, demonstrated that the P43 mutant
      was unable to secrete enterobactin efficiently. Products released from the mutant
      strain were identified with thin-layer chromatography (TLC) and high-performance
      liquid chromatography (HPLC), revealing that the P43 mutant secretes little, if
      any, enterobactin, but elevated levels of enterobactin breakdown products 2,3-
      dihydroxybenzoylserine (DHBS) monomer, dimer, and trimer. These data establish
      that P43 is a critical component of the E. coli enterobactin secretion machinery
      and provides a rationale for the designation of the previous genetic locus ybdA
      as entS to reflect its relevant biological function.

PMID- 12068808
TI  - Autoinduction of the ompR response regulator by acid shock and control of the
      Salmonella enterica acid tolerance response.
AB  - Salmonella enterica serovar Typhimurium periodically experiences acid stress in a
      variety of host and non-host environments. An encounter with non-lethal acid
      stress (pH > 4) induces an assortment of physiological changes, called the acid
      tolerance response (ATR), that helps the cell to tolerate extreme low pH (pH 3).
      These physiological changes differ in log phase and stationary phase cells and
      are controlled by different regulatory proteins. OmpR is an acid-induced response
      regulator critical to the stationary phase ATR but not to the log phase ATR. As
      OmpR also controls the expression of the acid-induced virulence operon ssrAB,
      acid shock induction of ompR was examined to gain insight into how Salmonella
      links virulence with survival at extreme acid pH. The results indicate that acid
      pH induces ompR from a promoter different from that used for basal expression.
      Transcription from this promoter is repressed by the histone-like protein H-NS
      and requires OmpR-P for induction. The classic sensor kinase EnvZ and acetyl
      phosphate collaborate to produce the optimum level of OmpR-P needed for
      autoinduction. Although OmpR-P is required for acid-induced expression of ompR in
      wild-type cells, OmpR is not needed for ompR transcription in the absence of H
      NS. Thus, the role of OmpR-P in autoinduction is to help to counteract repression
      by H-NS. This evidence, combined with the finding that relaxing DNA supercoiling
      with novobiocin also increased ompR transcription, suggests that acid stress
      induces ompR by altering local DNA topology, not by changing the phosphorylation
      status of OmpR.

PMID- 12068810
TI  - Expression of the Escherichia coli pcnB gene is translationally limited using an
      inefficient start codon: a second chromosomal example of translation initiated at
      AUU.
AB  - Expression of the gene pcnB, encoding the dispensable Escherichia coli poly(A)
      polymerase (PAPI), which is toxic when overproduced, was investigated. Its
      promoter was identified and found to be moderately strong when used to express a
      beta-galactosidase reporter. Expression levels were not affected by increasing or
      decreasing PcnB concentration. Translation of pcnB was found to initiate from the
      non-canonical initiation codon AUU. The only other coli gene reported to use AUU
      as initiation codon is infC, which encodes the initiation factor IF-3. AUU, in
      common with other rarely used initiation codons, is discriminated against by IF
      3, resulting in the aborting of most AUU-promoted initiation events. This enables
      AUU to form part of an autoregulatory circuit controlling IF-3 production. We
      show that InfC discrimination reduces PcnB production fivefold. This is the first
      instance of this mechanism being used to limit severely the production of a
      potentially toxic product.

PMID- 12068809
TI  - Protein engineering modulates the transport properties and ion selectivity of the
      pores formed by staphylococcal gamma-haemolysins in lipid membranes.
AB  - Staphylococcal gamma-haemolysins are bicomponent toxins in a family including
      other leucocidins and alpha-toxin. Two active toxins are formed combining HlgA or
      HlgC with HlgB. Both open pores in lipid membranes with conductance, current
      voltage characteristics and stability similar to alpha-toxin, but different
      selectivity (cation instead of anion). Structural analogies between gamma
      haemolysins and alpha-toxin indicate the presence, at the pore entry, of a
      conserved region containing four positive charges in alpha-toxin, but either
      positive or negative in gamma-haemolysins. Four mutants were produced (HlgA D44K,
      HlgB D47K, HlgB D49K and HlgB D47K/D49K) converting those negative charges to
      positive in HlgA and HlgB. When all charges were positive, the pores had the same
      selectivity and conductance as alpha-toxin, suggesting that the cluster may form
      an entrance electrostatic filter. As mutated HlgC-HlgB pores were less affected,
      additional charges in the lumen of the pore were changed (HlgB E107Q, HlgB D121N,
      HlgB T136D and HlgA K108T). Removing a negative charge from the lumen made the
      selectivity of both HlgA-HlgB D121N and HlgC-HlgB D121N more anionic. Residue
      D121 of HlgB is compensated by a positive residue (HlgA K108) in the HlgA-HlgB
      pore, but isolated in the more cation-selective HlgC-HlgB pore. Interestingly,
      the pore formed by HlgA K108T-HlgB, in which the positive charge of HlgA was
      removed, was as cation selective as HlgC-HlgB. Meanwhile, the pore formed by HlgA
      K108T-HlgB D121N, in which the two charge changes compensated, retrieved the
      properties of wild-type HlgA-HlgB. We conclude that the conductance and
      selectivity of the gamma-haemolysin pores depend substantially on the presence
      and location of charged residues in the channel.

PMID- 12068811
TI  - Topology of the Salmonella invasion protein SipB in a model bilayer.
AB  - A critical early event in Salmonella infection is entry into intestinal
      epithelial cells. The Salmonella invasion protein SipB is required for the
      delivery of bacterial effector proteins into target eukaryotic cells, which
      subvert signal transduction pathways and cytoskeletal dynamics. SipB inserts into
      the host plasma membrane during infection, and the purified protein has membrane
      affinity and heterotypic membrane fusion activity in vitro. We used complementary
      biochemical and biophysical techniques to investigate the topology of purified
      SipB in a model membrane. We show that the 593 residue SipB is predominantly
      alpha-helical in aqueous solution, and that no significant change in secondary
      structural content accompanies lipid interaction. SipB contains two -helical
      transmembrane domains (residues 320-353 and 409-427), which insert deeply into
      the bilayer. Their integration allowed the hydrophilic region between the
      hydrophobic domains (354-408) to cross the bilayer. SipB membrane integration
      required both the hydrophobic domains and an additional helical C-terminal region
      (428-593). Further spectroscopic analysis of these domains in isolation showed
      that the hydrophobic regions insert obliquely into the bilayer, whereas the C
      terminal domain associates with the bilayer surface, tilted parallel to the
      membrane. The combined data suggest a topological model for membrane-inserted
      SipB.

PMID- 12068812
TI  - Both metal binding sites in the homodimer are required for metalloregulation by
      the CadC repressor.
AB  - The cadCA operon of plasmid pI258, which confers resistance to the soft metals
      Cd(II), Pb(II) and Zn(II), is regulated by CadC, a metal-responsive
      transcriptional repressor. CadC is a 27.6 kDa homodimer composed of two 122
      residue monomers. Three cysteine residues, Cys-7, Cys-58 and Cys-60, have been
      shown to be required for sensing soft metals. Thus, the repressor has two
      potential inducer binding sites, one on each monomer. However, it is not known
      whether both binding sites are required for derepression or whether binding of
      metal to a single site would result in transcript. In this study, heterodimers
      were purified in which one binding site was wild type and the other had
      substitutions of the cysteine residues. The wild type-mutant heterodimers
      retained the ability to bind to cad operator/promoter DNA but did not dissociate
      from the DNA upon addition of soft metal ions. The results indicate that both
      subunits in the dimer must have functional metal binding sites for metal sensing
      to lead to derepression

PMID- 12068813
TI  - The datA locus predominantly contributes to the initiator titration mechanism in
      the control of replication initiation in Escherichia coli.
AB  - Replication of the Escherichia coli chromosome is initiated synchronously from
      all origins (oriC) present in a cell at a fixed time in the cell cycle under
      given steady state culture conditions. A mechanism to ensure the cyclic
      initiation events operates through the chromosomal site, datA, which titrates
      exceptionally large amounts of the bacterial initiator protein, DnaA, to prevent
      overinitiation. Deletion of the datA locus results in extra initiations and
      altered temporal control of replication. There are many other sites on the E.
      coli chromosome that can bind DnaA protein, but the contribution of these sites
      to the control of replication initiation has not been investigated. In the
      present study, seven major DnaA binding sites other than datA have been examined
      for their influence on the timing of replication initiation. Disruption of these
      seven major binding sites, either individually or together, had no effect on the
      timing of initiation of replication. Thus, datA seems to be a unique site that
      adjusts the balance between free and bound DnaA to ensure that there is only a
      single initiation event in each bacterial cell cycle. Mutation either in the
      second or the third DnaA box (a 9 basepair DnaA-binding sequence) in datA was
      enough to induce asynchronous and extra initiations of replication to a similar
      extent as that observed with the datA-deleted strain. These DnaA boxes may act as
      cores for the cooperative binding of DnaA to the entire datA region.

PMID- 12068814
TI  - Mutual dependence of the expression of the cell differentiation regulatory
      protein HetR and the global nitrogen regulator NtcA during heterocyst
      development.
AB  - Heterocyst differentiation in the cyanobacterium Anabaena sp. strain PCC 7120
      depends on both the global nitrogen regulator NtcA and the cell differentiation
      regulatory protein HetR, and induction of hetR upon nitrogen step-down depends on
      NtcA. The use of two out of the four transcription start points (tsps) described
      for the hetR gene (those located at positions -728 and -271) was found to be
      dependent on NtcA, and the use of the tsp located at position -271 was also
      dependent on HetR. Thus, autoregulation of hetR could take place via the
      activation of transcription from this tsp. Expression of ntcA in nitrogen-fixing
      cultures was higher than in cells growing in the presence of ammonium or nitrate,
      and high expression of ntcA under nitrogen deficiency resulted from an increased
      use of tsps located at positions -180 and -49. The induction of the use of these
      tsps did not take place in ntcA or hetR mutant strains. These results indicate a
      mutual dependency in the induction of the regulatory genes hetR and ntcA that
      takes place in response to nitrogen step-down in Anabaena cells. Expression of
      the hetC gene, which is also involved in the early steps of heterocyst
      differentiation, from its NtcA-dependent tsp was, however, not dependent on HetR.

PMID- 12068815
TI  - Effects of ribosomal proteins S1, S2 and the DeaD/CsdA DEAD-box helicase on
      translation of leaderless and canonical mRNAs in Escherichia coli.
AB  - Leaderless mRNAs beginning with the AUG initiating codon occur in all kingdoms of
      life. It has been previously reported that translation of the leaderless cI mRNA
      is stimulated in an Escherichia coli rpsB mutant deficient in ribosomal protein
      S2. Here, we have studied this phenomenon at the molecular level by making use of
      an E. coli rpsB(ts) mutant. The analysis of the ribosomes isolated under the non
      permissive conditions revealed that in addition to ribosomal protein S2,
      ribosomal protein S1 was absent, demonstrating that S2 is essential for binding
      of S1 to the 30S ribosomal subunit. In vitro translation assays and the selective
      translation of a leaderless mRNA in vivo at the non-permissive temperature
      corroborate and extend previous in vitro ribosome binding studies in that S1 is
      indeed dispensable for translation of leaderless mRNAs. The deaD/csdA gene,
      encoding the "DeaD/CsdA" DEAD-box helicase, has been isolated as a multicopy
      suppressor of rpsB(ts) mutations. Here, we show that expression of a plasmid
      borne DeaD/CsdA gene restores both S1 and S2 on the ribosome at the non
      permissive temperature in the rpsB(ts) strain, which in turn leads to suppression
      of the translational defect affecting canonical mRNSa. These data are discussed
      in terms of a model, wherein DeaD/CsdA is involved in ribosome biogenesis rather
      than acting directly on mRNA.

PMID- 12068816
TI  - SecDFyajC forms a heterotetrameric complex with YidC.
AB  - The Escherichia coli preprotein translocase is composed of a "preprotein
      conducting channel" domain that consists of the peripherally bound translocation
      ATPase SecA and the heterotrimeric SecYEG membrane protein complex. SecD, SecF,
      and YajC form another heterotrimeric complex that can associate with the SecYEG
      complex. YidC is an essential membrane protein that plays a role in the
      integration of newly synthesized membrane proteins, and has been shown to co
      purify with SecYEG when all translocase components are overproduced. Here, we
      demonstrate that under conditions that YidC co-purifies with overproduced
      SecDFyajC it does not co-purify with overproduced SecYEG. Moreover, this
      interaction of YidC with the SecDFyajC complex is also found at chromosomal
      protein levels of SecD, SecF and YajC. Closer examination of the SecDFyajC-YidC
      complex showed that YidC binds to SecD and SecF, whereas YajC interacts only with
      SecF. As SecF and YajC have previously been shown to interact with SecY, we
      propose that these two proteins link the heterotetrameric SecDFyajC-YidC complex
      to the SecYEG complex.

PMID- 12068817
TI  - Hailing one of healthcare's priceless resources--nurses.

PMID- 12068818
TI  - Bibliography. Current world literature. Fertility.

PMID- 12068819
TI  - Bibliography. Current world literature. Reproductive endocrinology.

PMID- 12068820
TI  - Bibliography. Current world literature. Demyelinating diseases.

PMID- 12068821
TI  - Bibliography. Current world literature. Headache.

PMID- 12068822
TI  - Bibliography. Current world literature. Inflammatory diseases.

PMID- 12068823
TI  - [Asymmetry. Part 2. 75th Scientific Meeting of the French Society of Dento-Facial
      Orthopedics. Biarritz, 8-11 May 2002].

PMID- 12068824
TI  - [Asymmetry. Part I. 75th Scientific Meeting of the French Society of Dento-Facial
      Orthopedics. Biarritz, 8-11 May 2002].

PMID- 12068825
TI  - [Regional meeting of the Japanese ophthalmological Society. Japan. 2001.
      Abstracts].

PMID- 12068826
TI  - Roundtable discussion: problems in the management of hypertension.

PMID- 12068827
TI  - What makes something a nursing activity or task.

PMID- 12068828
TI  - The nursing shortage: short and long term solutions.

PMID- 12068829
TI  - "The nursing shortage: is this cycle different?".

PMID- 12068830
TI  - Seeking progressive care solutions.

PMID- 12068831
TI  - Do nontriploid partial hydatidiform moles exist? A histologic and flow cytometric
      reevaluation of nontriploid specimens.
AB  - OBJECTIVE: To study whether nontriploid partial hydatidiform moles truly exist.
      STUDY DESIGN: We conducted a reevaluation of pathology and ploidy in 19 putative
      nontriploid partial hydatidiform moles using standardized histologic diagnostic
      criteria and repeat flow cytometric testing by the Hedley technique. RESULTS: On
      review of the 19 moles, 53% (10/19) were diploid nonpartial moles (initially
      pathologically misclassified), and 37% (7/19) were triploid partial moles
      (initial ploidy misclassifications). One additional case (5%) was a diploid early
      complete mole (initially pathologically misclassified). CONCLUSION: Nontriploid
      partial moles probably do not exist: careful reevaluation of putative specimens
      will probably uncover pathologic or ploid errors in almost all cases.

PMID- 12068832
TI  - Every man his own farrier in Australia: the origins and growth of a veterinary
      business in colonial New South Wales.
AB  - The life and work is told of John Pottie (1832-1908), a Scotsman who graduated
      from Edinburgh Veterinary College in 1858. A year later, he contracted to provide
      veterinary care to a consignment of horses bound for Australia. Once there, he
      founded a firm that has survived to the present day, still marketing products
      that originated in his own veterinary remedies. John Pottie brought with him a
      European tradition of livestock care and treatment that was epitomised in
      Clater's title and book, Every man his own farrier. His career is of interest for
      several reasons. Firstly it is because he used this tradition to launch a
      business enterprise in a new and different market in Australia. Secondly,
      although his training lay in what may be termed the pre-scientific era of the
      profession's history, he was able to adapt old traditions successfully to the
      changes that came in the age of Pasteur and Koch. Finally, the manner in which he
      did this, besides demonstrating his business acumen, also shows how the
      professional veterinary qualification gained in value in a new age of science.

PMID- 12068833
TI  - Rural crisis circa 1960s. 1968.

PMID- 12068834
TI  - Hindsight bias in medicolegal expert reports.

PMID- 12068835
TI  - Fatalities from bread tag ingestion.

PMID- 12068836
TI  - Bioethics and research in Africa.

PMID- 12068837
TI  - Repairing the brain - which stem cells to use?

PMID- 12068839
TI  - Sertraline: new indication. May help children with obsessive-compulsive disorder.
AB  - (1) The choice of treatment for children with obsessive-compulsive disorder is
      difficult. Behaviour therapy and antidepressants have not been assessed
      adequately in this setting, and their efficacy seems limited. Clomipramine was
      the first antidepressant to show a degree of efficacy. (2) Sertraline is the
      first drug to be licensed in France for children aged from 6 to 17 years with
      obsessive-compulsive disorder. (3) According to our literature search, the
      evaluation file on sertraline in this indication mainly contains data from a
      double-blind placebo-controlled trial involving 187 children. After 3 months of
      treatment, sertraline was significantly more effective than placebo, although
      most children remained symptomatic. Direct comparison is lacking, but sertraline
      seems as effective as clomipramine. (4) However, 13% of children receiving
      sertraline left this trial because of adverse events (3% on placebo; p = 0.02).
      The short-term safety profile of sertraline in children is the same as in adults,
      i.e. mainly nausea, agitation, headache, insomnia and tremor. (5) We have no data
      on the effects of prolonged sertraline therapy in children, particularly on
      neuropsychological development. (6) The first-line treatment of obsessive
      compulsive disorder is behaviour therapy. Sertraline, like clomipramine, is an
      option when behaviour therapy fails or is unfeasible. The choice between
      sertraline and clomipramine should be discussed case by case, according to their
      safety profiles; however, we have more experience with clomipramine, which should
      therefore be preferred over sertraline.

PMID- 12068838
TI  - Ursodeoxycholic acid: a second look. Primary biliary cirrhosis: dashed hopes.
AB  - (1) In 1996 the evidence, though limited, suggested that the hydrophilic bile
      acid ursodeoxycholic acid slowed the progression of primary biliary cirrhosis.
      Given the absence of an effective alternative, we considered that the treatment
      was "A real advance" in this setting. (2) The file is far bulkier now. A meta
      analysis of 11 randomised placebo-controlled trials of ursodeoxycholic acid in
      the treatment of primary biliary cirrhosis did not show efficacy. Histologically,
      the data suggest that the drug lowers the risk of hepatic fibrosis, but this is
      based on a low level of evidence. Moreover, there was no clinical improvement in
      the longest randomised trial (median follow-up 3.4 years). (3) Likewise,
      ursodeoxycholic acid seems to have a biochemical effect but no clear clinical
      effect in sclerosing cholangitis or in treating the hepatic complications of
      cystic fibrosis. (4) The main adverse effects are gastrointestinal disorders. (5)
      There are still no drugs clearly capable of slowing the clinical progression of
      primary biliary cirrhosis. Nevertheless, given the minor adverse effects of
      ursodeoxycholic acid, some patients may wish to gamble on a possible benefit in
      the very long term. (6) When primary biliary cirrhosis becomes symptomatic (with
      encephalopathy, osteomalacia, etc.) pending liver transplantation, treatment is
      aimed at controlling symptoms and preventing the rupture of oesophageal varices.

PMID- 12068840
TI  - Combined acellular pertussis vaccines: new indication. No tangible benefit in
      primary vaccination.
AB  - (1) Two acellular pertussis vaccines included in pentavalent combinations are
      available in France. Their use was initially restricted to booster injections.
      This restriction has now been lifted, meaning that the two products can be used
      for primary vaccination. (2) The initial assessment files, which mainly concerned
      primary vaccination, showed that the acellular pertussis vaccines had fewer mild
      side effects than the cellular vaccine, but there was no evidence that they were
      as effective. (3) Some epidemiological studies with fairly short follow-up (about
      2 years), conducted in various countries, suggest that the acellular vaccines
      confer clinical protection. There are no data comparing the bi- and tri-antigenic
      acellular vaccines marketed in France. (4) For the time being, the whole-cell
      pertussis vaccine remains the standard.

PMID- 12068841
TI  - Sublingual apomorphine: new preparation. In erectile disorders: a narrow
      therapeutic margin.
AB  - (1) When drug treatment is indicated for erectile dysfunction, sildenafil is the
      first line oral treatment. Overall, about half of patients with erectile
      dysfunction can achieve satisfactory penetrative sex with sildenafil. (2)
      Apomorphine, a dopamine agonist, is now licensed in France for treatment of
      erectile dysfunction. It is available as sublingual tablets of 2 mg and 3 mg. (3)
      The evaluation dossier contains no data comparing apomorphine with sildenafil.
      Dose-finding studies and placebo-controlled trials in patients without a serious
      organic disorder show that about 90% consider the 2 mg dose of apomorphine to be
      insufficient. The 3-mg tablets are hardly more effective. Nearly 90% of patients
      prefer a dose of at least 4 mg. (4) The main side effects of sublingual
      apomorphine are nausea, dizziness, severe sweating and drowsiness. These effects
      are dose-dependent. Syncope and hypotension are also relatively common. Serious
      consequences of these side effects were reported during some clinical trials. (5)
      The safety profile of sublingual apomorphine is no better than that of
      sildenafil. Both drugs interact with nitrates, increasing the risk of
      hypotension. (6) In practice, sildenafil remains the first line treatment for men
      with erectile dysfunction.

PMID- 12068842
TI  - Tibolone: new preparation. Menopausal symptoms: oestrogen-progestogen
      combinations are still the reference treatment.
AB  - (1) For symptoms of oestrogen deficiency linked to the menopause, the standard
      treatment is an oestrogen-progestogen combination. Various dose strengths and
      formulations are available for continuous or sequential administration. (2)
      Marketing authorization has been granted in France for continuous tibolone
      monotherapy (without a progestogen). Tibolone, a synthetic steroid with
      progestogenic, oestrogenic and androgenic properties, has been available in some
      countries for more than 10 years. (3) The available clinical file mainly
      comprises data from trials with a low level of evidence. The largest trial,
      involving 437 patients, showed no difference in symptom relief between tibolone
      and continuous oestrogen-progestogen administration. (4) The most frequent short
      term side effects of tibolone are irregular bleeding (in approximately 30% of
      women), oedema, breast tension and nausea. (5) No long-term data on the risk of
      breast cancer are available, and data on the risks of endometrial cancer are
      inadequate. The androgenic lipid profile induced by tibolone is unfavourable
      (reduction in HDL-cholesterol). Tibolone has a positive effect on bone density,
      but subsequent effects on the risk of fracture have barely been assessed. (6) In
      practice, tibolone has no particular advantages over oestrogen-progestogen
      combinations. On the contrary, it bears a poorly assessed risk of severe adverse
      reactions. Oestrogen-progestogen combinations remain the reference treatment for
      treating menopausal symptoms.

PMID- 12068843
TI  - Tenecteplase: new preparation. Another thrombolytic agent for myocardial
      infarction: a slightly simpler treatment.
AB  - (1) Alteplase is the standard thrombolytic agent for treating patients under 75
      years with myocardial infarction if they are seen within 6 hours. It is given as
      an intravenous infusion over 90 minutes in combination with aspirin and
      unfractionated or low-molecular-weight heparin. (2) Tenecteplase has been
      authorized for use in myocardial infarction as an intravenous bolus over 5 to 10
      seconds. (3) The evaluation file on tenecteplase contains data from three dose
      finding studies and one double-blind trial against alteplase in nearly 17 000
      patients. The trial found no difference in mortality between the two treatments
      (6% at 30 days). Nor was there any substantial difference in serious adverse
      events (stroke, intracranial haemorrhage or heart failure). (4) Major haemorrhage
      was slightly less frequent in patients given tenecteplase, but there was no
      difference between groups in the incidence of intracranial haemorrhage or stroke.
      (5) A comparative trial suffering from a number of biases suggests that combined
      treatment with tenecteplase + enoxaparin has a similar risk-benefit ratio to
      combined treatment with tenecteplase + unfractionated heparin. The combination of
      tenecteplase and enoxaparin makes treatment simpler, which could be particularly
      useful prior to hospital admission. A smaller trial of alteplase + enoxaparin
      against alteplase + unfractionated heparin gave similar findings. (6) In
      practice, tenecteplase has the advantage of a more convenient administration; a
      very large trial strongly suggests that its effects are almost identical to those
      of alteplase.

PMID- 12068844
TI  - Coxibs + oral anticoagulants: risk of interaction.
AB  - (1) Concomitant use of a classical NSAID and a vitamin K antagonist carries a
      risk of bleeding. Some NSAIDs, and especially phenylbutazone, increase the INR.
      NSAIDs have antiplatelet effects and can cause gastrointestinal erosions and
      bleeding. (2) Celecoxib or rofecoxib in combination with an oral anticoagulant
      has been reported to increase the INR and, in some cases, to cause bleeding. The
      "coxibs" can also cause bleeding-prone gastrointestinal lesions. (3) If a coxib
      is combined with an oral anticoagulant then the INR must be watched closely.

PMID- 12068845
TI  - Renal impairment due to topical NSAIDS.
AB  - Several reports of renal impairment underline the risk of systemic adverse
      effects after application of nonsteroidal antiinflammatory drugs (NSAIDs) to the
      skin.

PMID- 12068846
TI  - Heart failure on infliximab.

PMID- 12068847
TI  - Dr Bupropion and Mr Amfebutamone.
AB  - The INN of amfebutamone has been changed, for reasons that are unclear.

PMID- 12068848
TI  - Severe tuberculosis while on infliximab (cont'd).
AB  - Reports of severe tuberculosis in patients treated with infliximab are
      increasing. The disease is often extrapulmonary.

PMID- 12068849
TI  - Creatine: little impact on athletic performance, but a risk of adverse effects.
AB  - (1) Creatine occurs naturally in the body. Some is derived from dietary sources,
      but endogenous synthesis covers individual requirements. Creatine deficiency
      occurs only in subjects with genetic disorders. (2) Oral creatine supplementation
      at supraphysiological doses seems to slightly improve the performance of some
      types of muscle exercise, but only those lasting less than 30 seconds; even this
      small effect is inconsistent. (3) The vague regulatory status of creatine
      supplements hinders effective monitoring of adverse events. Serious adverse
      events have been reported in people taking creatine supplements, but it's still
      unclear whether or not the creatine is responsible. Animal data suggest a link
      with cancer after long term exposure. (4) The precise composition of creatine
      supplements is unclear: contamination is possible, and other substances,
      especially doping agents, are sometimes added. (5) Taking creatine supplements is
      inadvisable.

PMID- 12068851
TI  - Missing data.

PMID- 12068852
TI  - Very late withdrawal of fluorides.

PMID- 12068850
TI  - Ecstasy and pregnancy: warn against ecstasy use.
AB  - Ecstasy users must be warned that the drug may be dangerous during pregnancy and
      is associated with increased risk of birth defects. Pregnancies exposed to
      ecstasy must be closely monitored.

PMID- 12068853
TI  - Tackling antibiotic waste.

PMID- 12068854
TI  - Lawyers poised to sue US junk food manufacturers.

PMID- 12068855
TI  - Polio cases rise in Nigeria as vaccine is shunned for fear of AIDS.

PMID- 12068856
TI  - Surgeon found liable for injuries because did not inform patient of risks.

PMID- 12068857
TI  - Welsh whistleblower is reinstated.

PMID- 12068859
TI  - R J Reynolds fined $20m for advertising to young people.

PMID- 12068860
TI  - US government supports Maine law to curb drug prices.

PMID- 12068861
TI  - Europe agrees plan for chemical terrorism alert system.

PMID- 12068862
TI  - UK consumers reject direct advertising to patients by drug industry.

PMID- 12068863
TI  - Organic meat products contaminated with carcinogenic herbicide.

PMID- 12068864
TI  - New ethical standards set for health service managers.

PMID- 12068866
TI  - Specialists attack government for not prioritising HIV.

PMID- 12068865
TI  - Childhood obesity in Canada has tripled in past 20 years.

PMID- 12068867
TI  - Public health doctors must press for health targets.

PMID- 12068868
TI  - Unhappy doctors. General practice must decide whether to be more proactive.

PMID- 12068869
TI  - Unhappy doctors. Unhappy doctors may become sick doctors.

PMID- 12068870
TI  - Unhappy doctors. Regarding sick people as consumers changes their role.

PMID- 12068871
TI  - Unhappy doctors. At least some of the unhappiness is due to excessive
      accountability.

PMID- 12068872
TI  - BMA negotiator calls for more male medical students. Plus ca change . . .

PMID- 12068873
TI  - Hip protectors. Integrated approach to care of older people is necessary.

PMID- 12068874
TI  - Hip protectors. Acceptability of hip protectors was 35% at six months in the
      community.

PMID- 12068875
TI  - Hip protectors. Rate of adherence is 42% at three months in residential homes.

PMID- 12068882
TI  - [Dynamic 3D reconstruction of Doppler flow ultrasound medical images].
AB  - OBJECTIVE: To implement dynamic 3D reconstruction of ultrasonic flow images by
      the technique of 3D reconstruction of ultrasonic medical images combined with
      Doppler flow imaging method. METHOD: Through analyzing the color-coded mode of
      Doppler flow images and utilizing the Color Bar in DFI provided by ultrasound
      system, the information of anatomical structure and blood flow velocity were
      separated from original DFI images. Then 3D reconstruction of blood velocity and
      its fusion display with 3D anatomical structure was implemented. RESULT: Clinical
      experiments showed that in vivo blood flow in heart cavity could be shown in 3D
      space simultaneously with anatomical structure of the heart, and the relationship
      between them was consistent with cardiology. The images rendered in such a way
      could show more medical information than that in traditional methods. CONCLUSION:
      The combination of 3D reconstruction of ultrasonic medical images and Doppler
      imaging technique could realize functional 3D reconstruction of ultrasonic
      medical images so as to give more medical information. It would have great
      potential application and present a new future for ultrasonic medical imaging.

PMID- 12068883
TI  - [A gait analysis system based on digital video and digital image processing].
AB  - OBJECTIVE: To provide a gait analysis system. METHOD: The system is composed of
      general video devices and personal computer hardware. The techniques of digital
      video and digital image processing such as template matching, sub-pixel and
      motion estimate etc were employed to identify and trace the markers. RESULT: A
      gait result of a cerebral palsy object, which consists of bar-figure, data, and
      video was provided. CONCLUSION: The gait analysis system based on digital video
      and digital image processing is easy to use, and can provide visual result, which
      is easy to understand.

PMID- 12068884
TI  - [Studies on character variation of parent of "Ganzaoxian 47" by space mutation].
AB  - OBJECTIVE: To breed a new variety from "86-70 selective line"--a late-maturing
      early indica rice variety with small spike, light grain and weak disease
      resistance by space mutation. METHOD: Dry seeds of "86-70 selective line" were
      carried by recoverable satellite, to a near earth orbit and sowed and planted on
      the earth after recovery, heritance and variation of the characters of SP1- SP9
      generation were observed. RESULT: Because of comprehensive space mutation, the
      characters of their progenies were segregated and varied in many aspects and
      directions, and the segregated and varied characters were found to be heritable;
      by selecting early-maturing mutants from these progenies and cultivating them
      directionally, a new rice variety "Ganzaoxian 47 " was bred. In comparison with
      its parent, "Ganzaoxian 47" had superior agronomic and economic characters,
      significantly strong resistance to rice blast and so on, its filled grains per
      spike [correction of spile], kilo-grain weight and yield were increased by 37.9%,
      5.3% and 22.5% respectively, but its growth and developmental duration were
      shortened by 14 d. CONCLUSION: This study provided a new demonstration for space
      mutation breeding by recoverable satellite, and indicated that space mutation was
      an effective and new approach to agricultural crops breeding.

PMID- 12068885
TI  - [The quantitative measurement of several main contaminants in sealed cabin].
AB  - OBJECTIVE: To establish a standardized analytical method of chromatography used
      for separating and determining six target contaminants including methyl alcohol,
      ethanol, glycol, acetic acid, acetone and benzene in space cabin simultaneously.
      METHOD: Optimal separating and examining conditions were determined through
      experiments by gas chromatography. Retention time was used to determine the
      nature of contamination and the method of extended standard to quantify
      accurately the six mixed contaminants. The method of five-point calibration was
      used. RESULT: Non-polar capillary GC column (30.00 m x 0.25 micrometers x 250
      micrometers) was selected. Oven temperature was -30 degrees C initially and then
      hoisted to 80 degrees C at a rate of 4 degrees C/min, to 150 degrees C at 6
      degrees C/min, to 250 degrees C at 10 degrees C/min and kept for 5 min. The
      temperature of flame ionization detector was 200 degrees C and that of back inlet
      adopting split mode was 150 degrees C. The linear correlation of calibration
      curve was satisfied and the precision of this method was high. CONCLUSION: Under
      optimal experimental conditions the chromatographic peaks of six contaminants
      were separated so completely that they were quantified accurately simultaneously.
      The results showed this method was simple, quick and accurate.

PMID- 12068886
TI  - [Upright tilt table testing and syncope evaluation].
AB  - Syncope is a state of unconsciousness, the process of syncope is sudden and
      transient. Transient and widespread cerebral ischemia/hypoxia are the reasons of
      syncope. Sixty percent to seventy percent of the patients suffering from syncope
      have no categorical reasoning, although lots of assisted examinations had been
      carried out. Those syncope are called unexplained syncope or unknown origin
      syncope. Basic upright tilt table test, as well as isoproterenol tilt table test,
      is a quite effective diagnostic technique for unexplained syncope. This paper
      reviewed the value of upright tilt [correction of tile] table test in diagnosing
      unexplained syncope. The method of experiment, information of it's clinical
      application and points for attention with test were also introduced.

PMID- 12068887
TI  - [Changes of leg compliance during weightlessness or simulated weightlessness].
AB  - Weightlessness or simulated weightlessness causes increase of leg compliance. It
      leads to more blood pooling in the legs and less blood returning to the heart
      during orthostatic test, which may partly explain the occurrence of orthostatic
      intolerance induced by weightlessness or simulated weightlessness. This article
      is a review covering published materials about the methods of measurement,
      mechanisms and countermeasures of the increase of leg compliance during
      weightlessness or simulated weightlessness.

PMID- 12068888
TI  - [Effects of nitric oxide on myocardial contraction function].
AB  - Nitric oxide (NO) produced by myocardial nitric oxide synthase has been
      implicated as a modulator of myocardial contraction [correction of contracion].
      This paper reviewed the reports on myocardial contraction modulated by NO, its
      mechanism, and regulation of expression and activity of iNOS. NO was recently
      shown to produce biphasic contractile [correction of contratile] effects on
      myocardium: augmentation at low levels and depression at high levels. The up
      regulation of inducible nitric oxide synthase (iNOS) often negatively modulates
      myocardial function.

PMID- 12068889
TI  - [Research progresses of the synthesis and application of oligopeptide containing
      Arg-Gly-Asp sequence].
AB  - Arg-Gly-Asp (RGD) is one of the oligopeptides with biological activity found in
      recent years. It is the minimum ammonia serial on the ligand, which can be
      recognized by most of the integrins. It has important influence on the
      recognition of endothelial cell, anti-thrombus and anti-tumour function, and the
      therapy of burn and skin helcosis. In this review, the synthesis and application
      of oligopeptide [correction of oligepoptide] containing RGD sequence were
      discussed.

PMID- 12068890
TI  - [Effects of head-down bedrest on surface temperature distribution and non
      evaporative heat dissipation].
AB  - OBJECTIVE: To study effect of simulated weightlessness on non-evaporative heat
      dissipation from different parts of the human body. METHOD: Body surface
      temperature distribution of five subjects was measured under -6 degrees head down
      bedrest for 7 d with HR-II infrared thermography. Non-evaporative heat
      dissipation was calculated with the heat exchange equations based on surface
      temperature. RESULT: The temperature difference between torso and extremities
      increased during bed rest, and the largest was 6.7 degrees C higher than the
      control on the 3rd day of bed rest. The part of non-evaporative heat dissipation
      from the torso increased about 6% and that from head-neck increased 2%. At the
      same time, the parts of heat dissipation from the upper and lower extremities
      decreased about 3% and 5% respectively. CONCLUSION: The parts of non-evaporative
      heat dissipation from different areas of the human body changed during simulated
      weightlessness. This result provided a basis for the flow distribution design of
      liquid cooling garment of EVA suit.

PMID- 12068891
TI  - Naming biology.
AB  - Historians of science recite familiar textbook stories about the origin of the
      term biology. With this note, Peter McLaughlin shows us antecedents that suggest
      it is worth thinking more about the traditions from which the familiar usage of
      the term emerged. We invited McLaughlin to submit this addition to our
      understanding of the foundation of "biology," and we thank him for his
      willingness to add to our knowledge in this way.

PMID- 12068892
TI  - The emergence of modern genetics in Spain and the effects of the Spanish Civil
      War (1936-1939) on its development.
AB  - The aim of this paper is to show how modern genetics reached Spain through the
      Junta para la Amplicion de Estudios e Investigaciones Cientificas (JAE) during
      the decade of 1920s, the role played by key persons, and the level of development
      this discipline achieved from its different points of inception and under the
      conditions of financial scarcity and political turmoil that prevailed during the
      Spanish Civil War (1936-1939). In addition, the effect of the war on the
      continuity of the lines of research already began is outlined, identifying the
      main area in which genetics first reappeared: agronomy.

PMID- 12068894
TI  - Harnessing heredity in Gilded Age America: middle class mores and industrial
      breeding in a cultural context.
AB  - By investigating the practices and beliefs of Gilded Age trotting horse breeders,
      this article demonstrates the relationship between industrial economic
      development and the growth of genetic reasoning in the United States. As most
      historians of biology already know, E. H. Harriman, Leland Stanford, and John D.
      Rockefeller not only transformed American business practice, they donated heavily
      to institutions that promoted eugenic research programs. What is not widely
      known, however, is that these same industrialists were accomplished trotting
      horse breeders with well-developed theories of inheritance. The article that
      follows uses these theories to place the rise of eugenic and genetic research
      into the context of the rapid development of industry in post Civil War America.
      Specifically, the study identifies how functional utility as defined through the
      narrow concerns of industrial practices were privileged over form and pedigree in
      American horse breeding. Even more importantly, this article suggests that the
      continuity established between the practices of the industrial philanthropists
      and the scientific research institutions that they established occurred at two
      levels: through the values privileged by the development of the dynamics of a
      mass society and through the tools used to process the large amounts of
      information necessary to understand breeding patterns in slow breeding organisms.

PMID- 12068893
TI  - To err and win a nobel prize: Paul Boyer, ATP synthase and the emergence of
      bioenergetics.
AB  - Paul Boyer shared a Nobel Prize in 1997 for his work on the mechanism of ATP
      synthase. His earlier work, though (which contributed indirectly to his triumph),
      included major errors, both experimental and theoretical. Two benchmark cases
      offer insight into how scientists err and how they deal with error. Boyer's work
      also parallels and illustrates the emergence of bioenergetics in the second half
      of the twentieth century, rivaling achievements in evolution and molecular
      biology.

PMID- 12068895
TI  - The task of explaining sight: Helmholtz's writings on vision as a test case for
      models of science popularization.
AB  - Studies of Helmholtz's popular lectures on science have concentrated on
      reconstructing his vision of the scientific enterprise, of its nature, its
      benefits, and its "civilizing power." This paper offers a different perspective
      by focusing on Helmholtz's attempts to expose his own scientific work to a wider
      public. Drawing on recent discussions about how to study science popularization,
      it analyzes how he made his work on sensory physiology accessible to various
      audiences. It is argued that the exposition of the theory of vision comprises a
      complex, multilayered transformation of epistemic messages, which includes the
      recasting of arguments, recontextualizations, shifting emphasis, and significant
      changes in style. The popular writings on vision were directed to several
      different audiences, and, as such, manifest a delicate balance between
      conflicting agendas. An analysis of the texts indicates that neither the
      traditional two-step model of science popularization nor the more recent attempt
      to regard popularization as an "expository continuum" provides appropriate
      historiographical frameworks to study the popularization of scientific knowledge.

PMID- 12068896
TI  - Physiological optics and physical geometry.
AB  - Hermann von Helmholtz's distinction between "pure intuitive" and "physical"
      geometry must be counted as the most influential of his many contributions to the
      philosophy of science. In a series of papers from the 1860s and 70s, Helmholtz
      argued against Kant's claim that our knowledge of Euclidean geometry was an a
      priori condition for empirical knowledge. He claimed that geometrical
      propositions could be meaningful only if they were taken to concern the behaviors
      of physical bodies used in measurement, from which it followed that it was
      posterior to our acquaintance with this behavior. This paper argues that
      Helmholtz's understanding of geometry was fundamentally shaped by his work in
      sense-physiology, above all on the continuum of colors. For in the course of that
      research, Helmholtz was forced to realize that the color-space had no inherent
      metrical structure. The latter was a product of axiomatic definitions of color
      addition and the empirical results of such additions. Helmholtz's development of
      these views is explained with detailed reference to the competing work of the
      mathematician Hermann Grassmann and that of the young James Clerk Maxwell. It is
      this separation between 1) essential properties of a continuum, 2) supplementary
      axioms concerning distance-measurement, and 3) the behaviors of the physical
      apparatus used to realize the axioms, which is definitive of Helmholtz's
      arguments concerning geometry.

PMID- 12068897
TI  - Helmholtz and the psychophysiology of time.
AB  - After having measured the velocity of the nervous impulse in the 1850s, Helmholtz
      began doing research on the temporal dimensions of visual perception. Experiments
      dealing with the velocity of propagation in nerves (as well as with aspects of
      perception) were carried out occasionally for some fifteen years until their
      final publication in 1871. Although the temporal dimension of perception seems to
      have interested Helmholtz less than problems of geometry and space, his
      experiments on the time of perception were technically rather subtle and seminal,
      especially compared with experiments performed by his contemporaries, such as
      Sigmund Exner, William James, Rudolf Hermann Lotze, Ernst Mach, Wilhelm Volkmann,
      and Wilhelm Wundt. Helmholtz's conception of the temporal aspects of perception
      reflects the continuity that holds between psychophysiological research and the
      Kantian philosophical background.

PMID- 12068898
TI  - Remarks on the context of Helmholtz's "Ueber das Wesen der Faulniss und Gahrung".

PMID- 12068899
TI  - Obstetric and gynecology devices; effective date of requirement for premarket
      approval for glans sheath devices. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to require the
      filing of a premarket approval application (PMA) or a notice of completion of
      product development protocol (PDP) for glans sheath medical devices. The agency
      has previously published its findings regarding the degree of risk of illness or
      injury designed to be eliminated or reduced by requiring the devices to meet the
      statute's approval requirements and the benefits to the public from the use of
      the devices.

PMID- 12068900
TI  - Medicaid program; Medicaid managed care. Withdrawal of final rule with comment
      period.
AB  - This document withdraws all provisions of the final rule with comment period on
      Medicaid managed care that we published in the Federal Register on January 19,
      2001 (66 FR 6228) with an initial effective date of April 19, 2001. This January
      19, 2001 final rule, which has never taken effect, would have combined Medicaid
      managed care regulations in a new part 438, implemented Medicaid managed care
      requirements of the Balanced Budget Act of 1997 (Pub. L. 105-33), and imposed new
      requirements on entities currently regulated as "prepaid health plans'' (PHPs).
      The regulations set forth in the final rule being withdrawn have been superseded
      by regulations promulgated in a subsequent rulemaking initiated on August 20,
      2001 (66 FR 43613). In addition, this document addresses comments received in
      response to an interim final rule with comment period that we published on August
      17, 2001 in the Federal Register (66 FR 43090) that further delayed, until August
      16, 2002, the effective date of the January 19, 2001 final rule with comment
      period.

PMID- 12068901
TI  - Medicaid program; Medicaid managed care: new provisions. Final rule.
AB  - This final rule amends the Medicaid regulations to implement provisions of the
      Balanced Budget Act of 1997 (BBA) that allow the States greater flexibility by
      permitting them to amend their State plan to require certain categories of
      Medicaid beneficiaries to enroll in managed care entities without obtaining
      waivers if beneficiary choice is provided; establish new beneficiary protections
      in areas such as quality assurance, grievance rights, and coverage of emergency
      services; and eliminate certain requirements viewed by State agencies as
      impediments to the growth of managed care programs, such as, the enrollment
      composition requirement, the right to disenroll without cause at any time, and
      the prohibition against enrollee cost-sharing.

PMID- 12068902
TI  - Seymour S. Kety: 25 August 1915 - 25 May 2000.

PMID- 12068903
TI  - James V. Neel: 22 March 1915 - 1 February 2000.

PMID- 12068904
TI  - The 1979 anthrax epidemic in the USSR: applied science and political controversy.

PMID- 12068905
TI  - A necessary inhumanity?
AB  - It is argued that the phrase "Necessary Inhumanity" more accurately describes the
      alienation required of doctors in some circumstances, than do modern sanitised
      coinages such as 'clinical detachment.' 'Detachment' and 'objectivity' imply
      separation, not engagement: creating distance not only from patients, but from
      the self: the process may well be required, but where it becomes too extreme or
      prolonged, it can damage everybody, including patients, family members, doctors
      themselves, and wider society. An awareness of the history of health care in the
      context of our society might assist self reflection--might help keep initiates in
      touch with the culture they have been induced to leave and might help them remain
      humane despite the bruising process of training.

PMID- 12068906
TI  - Conceptions of medical humanities.

PMID- 12068907
TI  - Don't cry for us Argentinians: two decades of teaching medical humanities.
AB  - Medical humanities--history, literature, anthropology, ethics and fine arts
      applied to medicine--play an important role in medical education. For more than
      20 years an effort has been made to obtain an academic identity for such a
      multidisciplinary approach. A distinction between humanitarianism and humanism is
      attempted here, the former being associated with medical care and the latter with
      medical education. In order more precisely to define the relationship between the
      arts and medicine, an alternative term "medical kalology", as-yet-unsanctioned,
      coined after the rules of medical terminology, is proposed. The Department of
      Medical Humanities in the School of Medicine, National University La Plata,
      submits the following apologia: Don't cry for us Argentinians, since the teaching
      of medical humanities has helped our doctors to function more truly
      humanistically during the past two decades, as we intend to continue with this
      calling in the future.

PMID- 12068908
TI  - Malpighi, Swammerdam and the colourful silkworm: replication and visual
      representation in early modern science.
AB  - In 1669, Malpighi published the first systematic dissection of an insect. The
      manuscript of this work contains a striking water-colour of the silkworm, which
      is described here for the first time. On repeating Malpighi's pioneering
      investigation, Swammerdam found what he thought were a number of errors, but was
      hampered by Malpighi's failure to explain his techniques. This may explain
      Swammerdam's subsequent description of his methods. In 1675, as he was about to
      abandon his scientific researches for a life of religious contemplation,
      Swammerdam destroyed his manuscript on the silkworm, but not before sending the
      drawings to Malpighi. These figures, with their rich and unique use of colour,
      are studied here for the first time. The role played by Henry Oldenburg,
      secretary of the Royal Society, in encouraging contact between the two men is
      emphasized and the way this exchange reveals the development of some key features
      of modern science - replication and modern scientific illustration - is
      discussed.

PMID- 12068909
TI  - The ethics of collegiality with special reference to Jewish sources.

PMID- 12068910
TI  - Physical culture in rabbinical literature in modern times.

PMID- 12068911
TI  - The impact of German Jewish physicians and German medicine on the origins and
      development of the medical faculty of the Hebrew University.
AB  - As we have shown, doctors from Central Europe, or at least trained in the Central
      European medical tradition, played an important role in the development of
      medicine at the Hebrew University Medical School, from its origins as the
      Hadassah-Rothchild Hospital to the present-day faculty of medicine. Although with
      Hadassah's involvement the American influence became more conspicuous, especially
      after 1945, the central European system remained important regarding manpower and
      innovative ideas. Many Jewish doctors who had trained in central Europe and had
      emigrated to Palestine had been leading figures in medical innovations in their
      home countries. In Israel they combined the German/Austrian medical tradition
      with the new American influence, which eventually became the most prominent.

PMID- 12068912
TI  - Thalidomide disaster: old wine in new bottles?

PMID- 12068913
TI  - The 'Doctrine of Salts' and Rev. John Walker's analysis of a Scottish spa (1749
      1761).

PMID- 12068914
TI  - Woodward, Robinson, and strychnine: chemical structure and chemists' challenge.

PMID- 12068915
TI  - Adequate controls for new drugs: good manufacturing practice and the 1938 federal
      Food, Drug, and Cosmetic Act.

PMID- 12068916
TI  - Medical supply at the Kongsberg Silver Mine in Norway before 1805.

PMID- 12068917
TI  - From germs to genes: trends in drug therapy, 1852-2002.

PMID- 12068918
TI  - EM visualization of Pol II genes in Drosophila: most genes terminate without
      prior 3' end cleavage of nascent transcripts.
AB  - Transcription termination by RNA polymerase II (Pol II) on most mRNA-encoding
      genes is dependent on transcription through a functional poly(A) signal. One
      model to explain this dependence predicts co-trancriptional cleavage of RNA at
      the poly(A) site. Electron microscopic (EM) visualization was used to investigate
      the in vivo frequency of transcript cleavage prior to termination. Over 100
      unidentified Drosophila Pol II-transcribed genes were analyzed. Although some
      genes exhibited cleaved transcripts near their 3' ends, and some had a lower
      polymerase density at their 3' end relative to the rest of the gene, the majority
      of genes (64%) had uncleaved transcripts and no change in polymerase density at
      the 3' end, consistent with release of full-length transcripts at a discrete
      site. Thus, in Drosophila, cleavage at the poly(A) site sometimes occurs co
      transcriptionally, but does not appear to be a prerequisite to termination. Next,
      two components of the polyadenylation complex were immunolocalized on polytene
      chromosomes and were found to differ in distribution both qualitatively and
      quantitatively. The EM results indicate that co-transcriptional recognition of
      the poly(A) signal, which is required for termination, does not equate with co
      transcriptional cleavage, and the immunofluorescence results suggest that this
      may be due to incomplete or nonstoichiometric assembly of the polyadenylation
      machinery on nascent transcripts.

PMID- 12068919
TI  - Stage-specific chromosomal association of Drosophila dMBD2/3 during genome
      activation.
AB  - The Drosophila gene dMBD2/3 encodes a protein with significant homologies to the
      mammalian methyl-DNA binding proteins MBD2 and MBD3. These proteins are essential
      components of chromatin complexes involved in epigenetic gene regulation. Because
      the available in vitro data on dMBD2/3 are conflicting we have started an in vivo
      characterization of dMBD2/3. We detected expression of two isoforms specifically
      during embryonic development. Staining of whole embryos combined with high
      resolution confocal microscopy revealed a highly regulated spatial distribution.
      During the syncytial blastoderm stage, dMBD2/3 formed speckles that localized to
      the cytoplasm. Shortly after, during the cellular blastoderm stage, the protein
      entered the nucleus and formed bright foci that associated with DNA. This rapid
      transition coincided with the activation of the embryonic genome. A similar
      observation was made during activation of the spermatocyte genome as dMBD2/3
      formed distinct foci associated with the activated Y chromosome. Our results
      indicate that dMBD2/3 forms specialized nuclear compartments to keep certain
      genes epigenetically silenced during genome activation.

PMID- 12068920
TI  - Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals.
AB  - We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of
      heterochromatin in divergent animal species. It localises to both constitutive
      and facultative heterochromatin and replicates late in S-phase of the cell cycle.
      Significantly, Me9H3 is enriched in the inactive mammalian X chromosome (Xi) in
      female cells, as well as in the XY body during meiosis in the male, and forms a G
      band pattern along the arms of the autosomes. Me9H3 is a constituent of imprinted
      chromosomes that are repressed. The paternal and maternal pronuclei in one-cell
      mouse embryos show a striking non-equivalence in Me9H3: the paternal pronucleus
      contains no immunocytologically detectable Me9H3. The levels of Me9H3 on the
      parental chromosomes only become equivalent after the two-cell stage. Finally, we
      provide evidence that Me9H3 is neither necessary nor sufficient for localisation
      of heterochromatin protein 1 (HP1) to chromosomal DNA.

PMID- 12068921
TI  - Complex relationships between 5-aza-dC induced DNA demethylation and chromosome
      compaction at mitosis.
AB  - A variety of treatments with 5-azadeoxycytidine (5-aza-dC) were applied to
      cultured human lymphocytes during one to four cell cycles. The effect of 5-aza-dC
      on DNA methylation was studied by using an antibody against 5-methylcytosine on
      mitotic chromosomes. 5-Azadeoxycytidine is known to induce strong and permanent
      demethylation of DNA. Unexpectedly complex relationships were observed between
      DNA methylation status and chromatid/chromosome compaction. The most dramatic
      alteration of compaction at mitosis was observed when pre-replicative chromosomes
      had unifilarly demethylated DNA. The compaction of chromosomes was found to
      depend only partially on the methylation of their DNA at the time of mitosis. Our
      results suggest that alteration of DNA methylation prevents the synchronization
      of chromatin compaction, inducing premature (or delayed) chromosome condensation,
      and that a crucial step is the DNA methylation status of the pre-replicative
      chromosome.

PMID- 12068922
TI  - Molecular and cytogenetic analysis of the telomeric (TTAGGG)n repetitive
      sequences in the Nile tilapia, Oreochromis niloticus (Teleostei: Cichlidae).
AB  - The majority of chromosomes in Oreochromis niloticus, as with most fish
      karyotyped to date, cannot be individually identified owing to their small size.
      As a first step in establishing a physical map for this important aquaculture
      species of tilapia we have analyzed the location of the vertebrate telomeric
      repeat sequence, (TTAGGG)n, in O. niloticus. Southern blot hybridization analysis
      and a Bal31 sensitivity assay confirm that the vertebrate telomeric repeat is
      indeed present at O. niloticus chromosomal ends with repeat tracts extending for
      4-10 kb on chromosomal ends in erythrocytes. Fluorescent in situ hybridization
      revealed that (TTAGGG)n is found not only at telomeres, but also at two
      interstitial loci on chromosome 1. These data support the hypothesis that
      chromosome 1, which is significantly larger than all the other chromosomes in the
      karyotype, was produced by the fusion of three chromosomes and explain the
      overall reduction of chromosomal number from the ancestral teleost karyotype of
      2n=48 to 2n=44 observed in tilapia.

PMID- 12068923
TI  - Expression and behaviour of CENP-E at kinetochores during mouse spermatogenesis.
AB  - Centromere protein E (CENP-E) is a microtubule motor protein localised in the
      outer kinetochore plate and in the fibrous corona that relocalises to the midzone
      in early anaphase. While its expression in somatic cells has been widely
      analysed, an accurate description of its behaviour during the two meiotic
      divisions has not yet been reported. We have carefully analysed by
      immunofluorescence the subcellular distribution of CENP-E during mouse
      spermatogenesis. CENP-E first appears during late diakinesis/early prometaphase I
      as very bright C-shaped or "crescent" signals at each homologous centromere.
      These crescent CENP-E signals are also observed in unaligned prometaphase I
      bivalents that are not attached to spindle microtubules, while in bioriented
      metaphase I bivalents two kinds of fainter signals are observed. Thus, some
      bivalents present a plate-like signal while others show a pair of spots
      representing sister kinetochores at each homologous centromere. Double labelling
      of CENP-E with CENP-G and an anti-centromere serum indicates that in meiosis CENP
      E is also located at the outer kinetochore plate and the fibrous corona. During
      early anaphase I CENP-E relocalises from kinetochores to the midzone where it is
      detected as fibrous strands, although some residual labelling persists at
      kinetochores until telophase I. During this stage CENP-E is detected as two
      parallel plates at the intercellular bridge. The general pattern of labelling
      during meiosis II is similar to that found during meiosis I. Our results suggest
      that CENP-E is implicated in the spindle checkpoint, and in chromosome alignment,
      during the two meiotic divisions in vertebrate males. We also demonstrate that
      the centromere changes its structure once alignment of all bivalents at the
      metaphase I plate has been reached.

PMID- 12068925
TI  - Bioconcentration and depuration of pyribenzoxim in common carp (Cyprinus carpio).

PMID- 12068924
TI  - Accessory nuclei revisited: the translocation of snRNPs from the germinal vesicle
      to the periphery of the future embryo.
AB  - Oocytes of certain insects contain peculiar organelles termed accessory nuclei
      (AN). These organelles originate by budding off from the envelope of the oocyte
      nucleus and contain 1-2 dense inclusions immersed in a translucent ground
      substance. We have demonstrated that in the wasp Vespula germanica each inclusion
      consists of two elements: a spherical body, and a hemispherical structure
      composed of numerous 20-30 nm particles. Immunoelectron microscopy and whole
      mount in situ hybridization have shown that the inclusions contain AgNOR-staining
      proteins, p80-coilin, Sm proteins, and small nuclear RNAs (snRNAs). These results
      indicate that the inclusions and hemispherical structures are homologous to Cajal
      bodies and B-snurposomes of Xenopus germinal vesicles, respectively. During
      previtellogenesis, AN (together with their Cajal bodies) migrate to the cortical
      ooplasm of the oocyte where they reside at least until the onset of
      embryogenesis. We suggest that AN are vehicles for the transport and localization
      of snRNPs to the periphery of the oocyte, i.e., to the region where the
      blastoderm of the embryo develops and where there is a requirement for a high
      concentration of RNA-processing factors.

PMID- 12068926
TI  - Acute toxicity of water soluble fractions of crude oil to the Nile tilapia,
      Oreochromis niloticus (L.).

PMID- 12068927
TI  - Toxicity of chloroanilines and effects on superoxide dismutase activities in
      serum of crucian carp (Carassius auratus).

PMID- 12068928
TI  - Toxicity of linear alkyl benzenes (LABs) to the aquatic crustacean Daphnia magna
      through waterborne and food chain exposures.

PMID- 12068929
TI  - Stimulation of enzymatic defense mechanisms and appearance of liver damage in
      juvenile trout (Oncorhynchus mykiss) exposed to water-accommodated trace
      petroleum residues.

PMID- 12068930
TI  - Pesticide impact on excretory physiology of the common frog, Rana tigrina (Daud)
      tadpoles.

PMID- 12068932
TI  - Effect of salinity on acute toxicity of ammonia and nitrite to juvenile Mugil
      platanus.

PMID- 12068931
TI  - Alterations in retinoids, tocopherol, and microsomal enzyme activities in the
      liver of silver carp (Hypophthalmichthys molitrix) from Ya-Er Lake, China.

PMID- 12068934
TI  - Extraction, cleanup, and analysis of the perchlorate anion in tissue samples.

PMID- 12068933
TI  - Biochemical responses of Cassia siamea Lamk. grown on coal combustion residue
      (fly-ash).

PMID- 12068935
TI  - Effects of adjuvants on wetting and water infiltration of soils.

PMID- 12068936
TI  - Lichens as a good bioindicator of air pollution by mercury in small-scale gold
      mining areas, Tanzania.

PMID- 12068937
TI  - Chelate-assisted phytoextraction of lead from a contaminated soil using wheat
      (Triticum aestivum L.).

PMID- 12068938
TI  - Removal of mercuric chloride by a genetically engineered mercury-volatilizing
      bacterium Pseudomonas putida PpY101/pSR134.

PMID- 12068939
TI  - Fumonisin B1 levels in 1995 and 1996 Kansas corn.

PMID- 12068940
TI  - Persistence of endosulfan and endosulfan sulfate in soil as affected by moisture
      regime and organic matter addition.

PMID- 12068941
TI  - Catalytic photodegradation of endocrine disrupting chemicals using titanium
      dioxide photosemiconductor thin films.

PMID- 12068942
TI  - Organochlorine pesticide residues in mother's milk in Swaziland, 1996-1997.

PMID- 12068943
TI  - Monitoring of pesticide residues in farmgate and market samples of vegetables in
      a semiarid, irrigated area.

PMID- 12068944
TI  - Effect of heavy metals on the degradative activity by wood-rotting fungi.

PMID- 12068945
TI  - Toxicity of arsenate to the compostworm Eisenia fetida, the potworm Enchytraeus
      albidus and the springtail Folsomia candida.

PMID- 12068946
TI  - Persistence and effect of butachlor and basalin on the activities of phosphate
      solubilizing microorganisms in wetland rice soil.

PMID- 12068947
TI  - Developmental roles of heparan sulfate proteoglycans: a comparative review in
      Drosophila, mouse and human.
AB  - In recent years, progress in the fields of development and proteoglycan biology
      have produced converging evidence of the role of proteoglycans in morphogenesis.
      Numerous studies have demonstrated that proteoglycans are involved in several
      distinct morphogenetic pathways upon which they act at different levels. In
      particular, proteoglycans can determine the generation of morphogen gradients and
      be required for their signal transduction. The surface of most cells and the
      extracellular matrix are decorated by heparan sulfates which are the most common
      glycosaminoglycans, normally present as heparan sulfate proteoglycans.
      Considerable structural heterogeneity is generated in proteoglycans by the
      biosynthetic modification of their heparan sulfate chains as well as by the
      diverse nature of their different core proteins. This heterogeneity provides an
      impressive potential for protein-protein and protein-carbohydrate interactions,
      and can partly explain the diversity of proteoglycan involvement in different
      morphogenetic pathways. In this review, we summarize the current knowledge about
      mutations affecting heparan sulfate proteoglycans that influence the function of
      growth factor pathways essential for tissue assembly, differentiation and
      development. The comparison of data obtained in Drosophila, rodents and humans
      reveals that mutations affecting the proteoglycan core proteins or one of the
      biosynthetic enzymes of their heparan sulfate chains have profound effects on
      growth and morphogenesis. Further research will complete the picture, but current
      evidence shows that at the very least, heparan sulfate proteoglycans need to be
      counted as legitimate elements of morphogenetic pathways that have been
      maintained throughout evolution as determinant mechanisms of pattern formation.

PMID- 12068948
TI  - A dynamic requirement for community interactions during Xenopus myogenesis.
AB  - The community effect is an interaction among a group of many nearby cells that is
      necessary for them to maintain tissue-specific gene expression and differentiate
      co-ordinately. A community interaction is required for the muscle precursor cells
      of the Xenopus embryo to develop into terminally differentiated muscle, but
      exactly when and where the community effect acts during myogenesis has not been
      determined. Here, we ask whether dependence on the community effect varies with
      the developmental age of the muscle precursor cells. We find that dependence on
      the community signal changes with time through the muscle precursor cell
      population. During neurulation muscle precursor cells that are still in the
      vicinity of the blastopore and that are fated to form posterior muscle continue
      to require interactions with their neighbours, while differentiation of the
      anterior paraxial mesoderm,which gastrulated earlier, is independent of cell
      contact at this time. Thus the time during which a particular sub-population of
      muscle precursor cells requires a community interaction is related to their final
      destination along the anterior-posterior axis. In addition we show that this
      later acting community interaction around the blastopore involves FGF signalling.

PMID- 12068949
TI  - Retinal homeobox genes and the role of cell proliferation in cavefish eye
      degeneration.
AB  - The teleost Astyanax mexicanus exhibits eyed surface dwelling (surface fish) and
      blind cave dwelling (cavefish) forms. Despite lacking functional eyes as adults,
      cavefish embryos form eye primordia, which later arrest in development,
      degenerate and sink into the orbit. We are comparing the expression patterns of
      various eye regulatory genes during surfacefish and cavefish development to
      determine the cause of eye degeneration. Here we examine Rx and Chx/Vsx family
      homeobox genes, which have a major role in cell proliferation in the vertebrate
      retina. We isolated and sequenced a full-length RxcDNA clone (As-Rx1) and part of
      a Chx/Vsx(As-Vsx2) gene, which appear to be most closely related to the zebrafish
      Rx1 and Alx/Vsx2 genes respectively. In situ hybridization shows that these genes
      have similar but non-identical expression patterns during Astyanax eye
      development. Expression is first detected in the optic vesicle, then throughout
      the presumptive retina of the optic cup, and finally in the ciliary marginal zone
      (CMZ), the region of the growing retina where most new retinoblasts are formed.
      In addition, As-Rx1 is expressed in the outer nuclear layer (ONL) of the retina,
      which contains the photoreceptor cells, and As-Vsx2 is expressed in the inner
      nuclear layer, probably in the bipolar cells. With the exception of reduced As-Rx
      1 expression in the ONL, the As-Rx1 and As-Vsx2 expression patterns were
      unchanged in the developing retina of two different cavefish populations,
      suggesting that cell proliferation is not inhibited. These results were confirmed
      by using PCNA and BrdU markers for retinal cell division. We conclude that the
      CMZ is active in cell proliferation long after eye growth is diminished and is
      therefore not the major cause of eye degeneration.

PMID- 12068950
TI  - Expression of the mediators of dioxin toxicity, aryl hydrocarbon receptor (AHR)
      and the AHR nuclear translocator (ARNT), is developmentally regulated in mouse
      teeth.
AB  - Dioxins are persistent and ubiquitous environmental poisons that become enriched
      in the food chain. Besides being acutely lethal, the most toxic dioxin congener,
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), is developmentally toxic to many
      animal species. We have previously found that developing teeth of children may be
      sensitive to environmental dioxins via their mother's milk and that rat and mouse
      teeth are dioxin-sensitive throughout their development. The aryl hydrocarbon
      receptor (AHR) together with the AHR nuclear translocator (ARNT) protein is
      believed to mediate the toxic effects of dioxins. To study the potential
      involvement of the AHR-ARNT pathway in the dental toxicity of TCDD, we analysed
      the expression of AHR and ARNT by in situ hybridization and immunohistochemistry
      in developing mouse teeth. AHR mRNA first appeared in the epithelium of E12 first
      molar tooth buds and both proteins were weakly expressed in the bud. After
      cytodifferentiation the expression was up regulated and became intense in
      secretory odontoblasts and ameloblasts. The coexpression of AHR and ARNT during
      early tooth development as well as during the information and mineralization of
      the dental matrices is suggestive of the AHR-ARNT pathway as a mediator of dental
      toxicity of TCDD.

PMID- 12068951
TI  - A shoot meristem-like organ in animals; monopodial and sympodial growth in
      Hydrozoa.
AB  - Thecate Hydrozoa produce stems from which polyps branch off. Similar to plants
      these stems form in two ways, either in a sympodial or in a monopodial type of
      growth. In the latter group a terminal organ develops which has similarities to a
      shoot apical meristem of higher plants: it elongates without a further
      differentiation. Similar to leaf formation in plants, thecate Hydrozoa produce
      polyps in a repetitive manner. This process continues during the whole life of
      the animal and has not yet been found to be limited by internal mechanisms. We
      studied the monopodially growing thecate Hydrozoon Dynamena pumila and suggest
      that the stem tip, the apical shoot meristem-like organ, is a polyp primordium
      hindered to develop into a polyp by the laterally developing polyps.

PMID- 12068952
TI  - Selecting karyophilic DNA cis elements in Xenopus laevis oocytes; a new approach.
AB  - The intracellular localisation and mobility of exogenous DNA introduced into
      Xenopus laevis oocytes is largely unknown. In this paper, we report a new
      technique to investigate the cytoplasmic/nuclear transport of a random pool of
      linear, double-stranded, oligomeric DNA of 147 bp in length. We chose a
      combinatorial approach which made use of repetitive rounds of selection and
      amplification to search for new cis elements mediating nuclear import or
      retention. A new PCR-based methodology was established to reliably detect
      exogenous DNA in subcellular and total extracts prepared from Xenopus laevis
      oocytes. Studies in vivo and with cellular extracts indicate the presence of a
      highly efficient nuclease activity in the nuclear compartment. The described
      combinatorial approach constitutes a promising tool for the isolation of novel
      DNA cis elements which may play an important role in the nuclear internalisation
      and retention of exogenous DNA in Xenopus laevis oocytes.

PMID- 12068953
TI  - Histone methylation defines epigenetic asymmetry in the mouse zygote.
AB  - The oocyte cytoplasm regulates and enhances the epigenetic asymmetry between
      parental genomes and, consequently, functional differences observed between them
      during development in mammals. Here we demonstrate a preferential interaction of
      HP1beta with the maternal genome immediately after fertilisation in the mouse
      zygote, which also shows a high level of lysine 9-methylated histone H3. In
      contrast, the paternal genome has neither HP1beta binding nor methylated histone
      H3 at these early stages. Paternal binding of HP1beta is only detected at the
      pronuclear stage, prior to the appearance of lysine 9-methylated histone H3. The
      early recruitment of heterochromatic factors specifically to the maternal genome
      could explain the preferential DNA demethylation of the paternal genome in the
      zygote.

PMID- 12068954
TI  - The ash2 gene is involved in Drosophila wing development.
AB  - The absent small and homeotic (ash2) gene is a member of the trithorax group of
      positive transcriptional regulators of the homeotic genes. In this work we
      present evidence that loss-of-function of ash2 results in patterning alterations
      in the developing wing. Homozygous adults of the weak allele ash2(112411) develop
      extra cross-veins. However, clonal analysis of a stronger allele, ash2(11), shows
      that this allele results in reduction of intervein tissue and increase of
      longitudinal veins and cross-vein tissue in the wing except the region between
      vein L3 and L4. These results suggest that ash2 function is required for both
      activation of intervein tissue and repression of vein tissue. Moreover, we have
      found that cross-vein development can be rescued in the absence of crossveinless
      2 when the levels of ash2 were reduced.

PMID- 12068956
TI  - Planarian pharynx regeneration revealed by the expression of myosin heavy chain
      A.
AB  - The pharynx is a distinctive organ in the center of the body of planarians.
      Although the process of pharynx regeneration has been studied previously, the
      details and mechanism of the process remain controversial. We examined the
      process of regeneration of the pharynx in the planarian Dugesia japonica in
      detail by in situ hybridization and immunohistochemistry for myosin heavy chain-A
      (DjMHC-A), which is mainly expressed in the pharynx muscles and pharynx-anchoring
      muscles. We also monitored the behavior of the neoblasts in this process. In the
      regenerating posterior body fragment, the pharyngeal rudiment was formed by
      accumulation of cells that were probably undifferentiated cells derived from the
      neoblasts. The pharynx muscles appeared to differentiate in the rudiment in a
      manner that was coordinated with the differentiation of the pharynx-anchoring
      muscles in the region surrounding the rudiment. During this process, all cells
      containing mRNA for DjMHC-A also contained the DjMHC-A protein. These results
      argue against a previously proposed hypothesis that in the mesenchyme, 'pharynx
      forming cells', which are committed to differentiate into the pharyngeal cells
      but have not yet differentiated, gather in the rudiment to form the pharynx
      (Agata and Watanabe, 1999). Rather, the present observations suggest that
      regeneration of the planarian pharynx proceeds by accumulation of cells that are
      probably undifferentiated cells derived from neoblasts in the rudiment, followed
      by their differentiation into the pharyngeal cells there.

PMID- 12068958
TI  - Robbing tomorrow's generations.

PMID- 12068955
TI  - Retinoic acid response element in HOXA-7 regulatory region affects the rate, not
      the formation of anterior boundary expression.
AB  - Since it is known that a 307 bp fragment of the position specific regulatory
      element of human HOXA-7 contains two (DR3 and DR5) retinoic acid response
      elements (RAREs) at its 3' end, we constructed several deletion constructs
      containing different numbers of RAREs and examined their effects in vitro and in
      vivo. The 5' deletion constructs, BM112 and OM213, retaining both RAREs, were
      highly responsible (about 8 fold induction) for RA in F9 teratocarcinoma cells,
      versus NM307 (4-5 fold). The construct NS218, with both RAREs deleted but
      retaining the 5' sequences lost RA responsibility completely, whereas NR271, with
      one RARE(DR5) deleted retained a 50% inducibility (2.5 fold). In vivo transgenic
      analysis revealed that the constructs NM307 and NR271, but not OM213 nor BM112,
      directed the position specific expression pattern. Sequence analysis revealed
      that HOXA-7 enhancer sequences, including the RARE repeat sequences, were well
      conserved in human, mouse and chick. Part of the RAREs overlaps with the CDX1
      binding site, and sequences of the DR3 RAREs were identical in this species. Two
      GAGA binding sites were also found to be strictly conserved. Because OM213, which
      had one GAGA site disrupted but retaining both RAREs, did not direct anterior
      boundary formation in transgenic mice, these results suggest the importance of
      the 5' 94 bp region, including the GAGA binding site, in anterior boundary
      formation and the involvement of the RARE in the rate of expression not in
      anterior boundary formation.

PMID- 12068957
TI  - TGF-beta3 is required for the adhesion and intercalation of medial edge
      epithelial cells during palate fusion.
AB  - Transforming growth factor-beta3 (TGF-beta3) plays a critical role during palate
      development, since mutations of the TGF-beta3 gene give rise to cleft palate in
      both humans and mice. Striking alterations have been reported in the behaviour
      and differentiation of medial edge epithelial (MEE) cells in TGF-beta3 knockout
      mouse palates. In the present paper, we provide evidence of alterations in MEE
      intercellular adhesion in TGF-beta3 -/- mouse palates using immunohistochemistry
      with monoclonal antibodies to a panel of cell adhesion and cytoskeletal molecules
      including E-cadherin, alpha and beta catenin, beta actin, vinculin and beta2
      integrin. In vitro labeling of opposing MEE with two different lipophilic markers
      and subsequent analysis by confocal microscopy revealed that wild type MEE cells
      intercalate as soon as the midline epithelial seam forms. This finding indicates
      that the palate may elongate in a dorso-ventral direction by means of convergent
      extension, as occurs in other embryonic developmental processes. In contrast,
      this intercalation does not occur in the TGF-beta3 -/- MEE but it can be rescued
      by the exogenous addition of TGF-beta3. Thus, the substantial alteration of MEE
      intercellular adhesion observed in TGF-beta3 -/- palates may account for the
      defect in palatal shelf adhesion and the formation of cleft palate.

PMID- 12068959
TI  - Consumer response to a report card comparing healthcare systems.
AB  - OBJECTIVE: Report cards to date have focused on quality of care in health plans
      rather than within healthcare delivery systems. The purpose of this study was to
      evaluate consumer response to the first healthcare system-level report card.
      STUDY DESIGN: Qualitative assessment of consumer response. METHODS: We conducted
      5 focus groups of community members to evaluate consumer response to the report
      card; 2 included community club members, 3 included community-dwelling retired
      persons. Discussions were audiotaped and transcribed; comments were categorized
      by topic area from the script, and common themes identified. RESULTS: Focus group
      participants, in general, were unaware of the current emphasis on medical quality
      improvement initiatives. However, they believed that the opinion that the
      descriptive clinic information and patient survey data contained in the report
      card would be most useful mainly for choosing a healthcare system if they were
      dissatisfied with current medical care, if their healthcare options changed, or
      if they were in poor health. Personal experience was considered a more
      trustworthy measure of healthcare quality than were patient survey results.
      Trustworthiness was perceived to be higher if the report card sponsor was not
      affiliated with the healthcare systems being evaluated. Participants also
      believed care system administrators should use the data to enact positive clinic
      level and physician-level changes. CONCLUSIONS: Healthcare consumers appreciated
      the attention to patient experiences and supported healthcare quality improvement
      initiatives. Report cards were considered important for choosing a healthcare
      system in certain circumstances and for guiding quality improvement efforts at
      all levels.

PMID- 12068960
TI  - Screening for colorectal cancer: the business case.
AB  - Colorectal cancer screening is advocated by expert groups based on strong
      evidence of effectiveness, yet only approximately 1 in 3 Americans are screened.
      For a screening program to be effective, it is necessary for providers to offer
      and patients to accept screening, insurers to pay for screening, and provider
      groups to have monitoring and reminder systems and the expertise and facilities
      to perform the tests well. Whether and when such screening programs become
      successful depends on the priorities of healthcare decision makers as much as on
      the efforts of individual physicians and patients. There are strong arguments for
      decision makers giving colorectal cancer screening programs high priority: it
      saves as many lives as other services now in common use; it is a good use of
      scarce resources, costing less than $20,000 per year of life saved; and members
      of insurance programs increasingly expect screening benefits and programs, and
      failure to offer them might lead to member dissatisfaction and malpractice
      claims. Screening is costly, however, taking into account the cost of screening,
      follow-up tests, and treatments, and the costs occur many years before the
      benefits. Programs that are promoted to members but not fully implemented could
      create disappointment and backlash. Also, this screening can cause medical
      complications. Nevertheless, successful programs have been developed, proving
      that they are feasible in today's cost-conscious environment. We believe that
      colorectal cancer screening programs are integral to any organization purporting
      to provide high-quality care. Organizations without such programs should give
      them high priority for implementation.

PMID- 12068961
TI  - A nurse-based pilot program to reduce cardiovascular risk factors in a primary
      care setting.
AB  - OBJECTIVE: To evaluate the effectiveness of a nurse-based cardiovascular disease
      (CVD) risk factor reduction program among patients at a primary care outpatient
      clinic. STUDY DESIGN: Preintervention and postintervention longitudinal,
      prospective pilot study to evaluate patients' achievement of CVD risk factor
      reduction. PATIENTS AND METHODS: A total of 436 patients at a primary care clinic
      in suburban Minneapolis, Minnesota, were enrolled in 2 years; 286 patients were
      followed up with additional visits. The nurse intervention included comprehensive
      CVD risk assessment, patient education, and counseling. Algorithms guided the
      development of individualized care plans based on laboratory test values, blood
      pressure readings, tobacco use, and history of cardiovascular events. Physicians
      were consulted for serious changes in patients' medical conditions or for
      medication changes. Three measures were compared from baseline to the end of the
      program: blood pressure, low-density lipoprotein cholesterol levels, and tobacco
      use. RESULTS: Statistically significant reductions were achieved from baseline to
      the final nurse visit in systolic blood pressure (from 155.8 to 143.4 mm Hg),
      diastolic blood pressure (from 94.4 to 84.0 mm Hg), and dyslipidemia (low-density
      lipoprotein cholesterol, from 4.15 to 3.80 mmol/L [from 160 to 147 mg/dL]) (P <
      .001 for all). Of the 40 tobacco users who participated in the program, 12
      discontinued use (30%). CONCLUSIONS: This pilot study provides preliminary
      evidence of the effectiveness of a nurse-based CVD risk reduction program.
      Further study is needed to target high-risk patients and to compare results in
      the nurse intervention group with those in patients receiving usual care.

PMID- 12068962
TI  - Reduction in self-monitoring of blood glucose in persons with type 2 diabetes
      results in cost savings and no change in glycemic control.
AB  - OBJECTIVE: Recent Veterans Affairs (VA) guidelines recommend that persons with
      stable type 2 diabetes controlled on oral agents or diet therapy perform self
      monitoring of blood glucose (SMBG) twice weekly. We assessed the impact of a
      modification of these guidelines on hemoglobin A1c (HbA1c) and monitoring cost.
      STUDY DESIGN: Retrospective, noncrossover clinical trial. PATIENTS AND METHODS:
      We instructed persons with type 2 diabetes to perform SMBG testing according to
      modified adapted VA guidelines. We compared patients' baseline average testing
      frequency and HbA1c with those obtained during a 6-month interval beginning 2
      months after implementation of the modified guidelines. The impact on the cost of
      monitoring was calculated. RESULTS: At baseline, 913 of 1,213 SMBG users with
      diabetes on oral hypoglycemic agents had HbA1c tested (HbA1c = 7.83% +/- 1.34%);
      their frequency of SMBG was 1.36 +/- 0.95 strips per patient per day.
      Postimplementation, 974 of 1,278 persons with diabetes had HbA1c tested (HbA1c =
      7.86% +/- 1.54%; P= .63 vs baseline); frequency of SMBG decreased by 46% to 0.74
      +/- 0.50 strips per patient per day (P < .0001). At baseline, 154 of 254 SMBG
      users with diabetes on diet therapy had HbA1c tested (HbA1c = 6.85% +/- 0.97%);
      their frequency of SMBG was 1.07 +/- 0.90 strips per patient per day.
      Postimplementation, 177 of 282 diet-treated persons with diabetes had HbA1c
      tested (HbA1c = 6.78% +/- 1.20%; P = .56 vs baseline); frequency of SMBG
      decreased by 35% to 0.70 +/- 0.51 strips per patient per day (P < .0001). Similar
      findings were observed in a cohort of 421 drug-treated patients with paired HbA1c
      data before and after implementation, and a cohort of 50 diet-treated patients
      with paired HbA1c data. Linear regression analysis showed no significant impact
      on individuals' HbA1c with reduction in strip use. Average monthly cost savings
      were $8,800, or $6.37 per patient per month. CONCLUSIONS: This program decreased
      the frequency of SMBG in persons with type 2 diabetes, resulting in substantial
      cost savings without affecting glucose control.

PMID- 12068963
TI  - "My patients are sicker:" using the Pra risk survey for case finding and
      examining primary care site utilization patterns in a medicare-risk MCO.
AB  - BACKGROUND: The probability of repeat admissions (Pra) survey is a case-finding
      tool designed to identify elderly persons at risk for hospitalization. Little is
      known about the ability of the Pra to assess utilization patterns in a managed
      care setting. OBJECTIVES: To assess the ability of the Pra survey to identify
      elders at risk for increased healthcare costs and to determine the utility of
      this tool in predicting mean per member per year (PMPY) claims among primary care
      sites in a managed care setting. STUDY DESIGN: Mean PMPY paid claims, inpatient
      admissions, and inpatient days were compared for survey respondents with high,
      medium, and low Pra scores. Linear regression was used to examine the correlation
      (R2) between the mean Pra score for respondents and the percentage of high Pra
      score respondents at each primary care site in the HMO and the sites' mean PMPY
      paid claims. METHODS: From a single Medicare-risk health maintenance organization
      (HMO) with approximately 25,000 members and 234 primary care sites in
      northeastern and central Pennsylvania, we contacted 24,947 enrollees about the
      Pra survey. A total of 17,484 (70.1%) patients in 159 of 234 (67.9%) primary care
      sites responded to the survey. Of these, 17,469 (99%) surveys could be scored.
      RESULTS: The mean Pra score in this population was 0.27 (standard deviation =
      0.108). Pra scores were stratified as follows: 4.5%, 24.1%, and 71.4% of
      respondents scored high (20.5), moderate (> or = 0.3 and <0.5), and low (<0.3),
      respectively. Patients with high Pra scores had a mean of $12,611 in PMPY claims,
      versus $6944 and $3038 for moderate and low scores respectively (P < .0001). The
      R2 between the mean Pra score for respondents at each primary care site and the
      sites' mean PMPY Medicare-risk claims was 0.042. If survey respondents assigned
      to 6 specialty care sites (hematology, oncology, rheumatology, endocrinology,
      nephrology, and pulmonary medicine) are included, the R2 increased to 0.176. The
      R2 between the percentage of high-risk individuals with a Pra score of 0.5 or
      higher at each primary care site and the sites' mean PMPY Medicare-risk claims
      was 0.0005. CONCLUSIONS: In this Medicare-risk HMO population, the Pra survey
      successfully performed 2 functions: (1) the prospective identification of
      enrollees at risk for increased healthcare utilization and (2) identification of
      patient factors that accounted for as much as 17.6% of the variation in
      utilization between primary sites.

PMID- 12068964
TI  - The structure of self-rated health among community-dwelling older adults with
      stroke.
AB  - OBJECTIVE: To examine whether depressive symptomatology is a third fundamental
      component of the structure of self-rated health, in addition to two other
      components (physical disease and functional disability) among community-dwelling
      older adults with stroke. DATA SOURCES AND STUDY SETTING: A total of 591
      community-dwelling older adults with stroke were identified from the 1993 Asset
      and Health Dynamics among the Oldest-Old (AHEAD) national survey of community
      dwelling older adults. STUDY DESIGN: A cross-sectional study. Structural equation
      modeling was applied to compare a widely used two-factor model of self-rated
      health with a model adding depression as a third possible factor. PRINCIPLE
      FINDINGS: The hypothesized three-factor model explained additional 21% more
      variance of self-rated health of older adults with stroke (R2 = 79%, NNFI = 0.95,
      CFI = 0.96, RMSEA = 0.04) as compared with the two-factor biomedical model (R2 =
      58%, NNFI = 0.95, CFI = 0.98, RMSEA = 0.05). The three-factor model was
      statistically different from the two-factor model. CONCLUSIONS: Greater attention
      should be given to the theoretical structure of self-rated health of older adults
      with stroke, particularly, the significant impact of depression on their self
      rated health.

PMID- 12068965
TI  - Incidence of four adverse outcomes in the elderly population: implications for
      home care policy and research.
AB  - The cost-effective allocation of home care resources requires knowledge of the
      incidence of institutionalization, hospitalization, functional impairment, and
      mortality. We therefore assembled a database containing 176 rates abstracted from
      71 longitudinal studies published between 1985 and 1998 that examine one or more
      of these outcomes in the 65 and over population in the United States. Where
      possible we calculate median values for the estimated annual rate of each outcome
      for different types of studies-nationally representative, sub-national
      probability, and convenience sample-and specific subgroups-community residents,
      hospital admissions and discharges, and nursing home admissions and discharges.
      We find comparatively low rates of institutionalization and mortality, relatively
      high rates of hospitalization and functional impairment, similar rates for
      national and sub-national probability samples, and rates from convenience
      samples, which greatly exceed probability-based rates. While the rates for
      institutionalization, hospitalization and mortality are quite stable, the rates
      for functional impairment display considerably more variability. We conclude by
      discussing the implications of our findings for researchers and policymakers.

PMID- 12068966
TI  - The experience of empowerment in in-home services delivery.
AB  - In-home health services strive for client-centredness, involvement, and
      ultimately, empowerment, but economic constraint may undermine these aims. The
      purpose of this study was to explore the everyday experience of in-home care,
      with particular attention to the enactment of empowerment in the care
      partnership. In-depth interviews with a maximally varied sample of clients,
      informal caregivers, and providers uncovered relationships largely reflecting the
      traditional expert model of care. Findings afford insights into the unrecognized
      and undervalued personal knowledge of clients, caregivers, and in-home service
      providers, the professional and structural hegemony and consequent disempowered
      group behaviour of those who share the experience of care, and the hesitance of
      clients to engage as equitable partners in care. Strategies to achieve
      empowerment approaches to in-home health services are identified.

PMID- 12068967
TI  - How do they manage? Disabled elderly persons in the community who are not
      receiving Medicaid long-term care services.
AB  - OBJECTIVE: To expand our understanding of how low-income functionally impaired
      elderly persons are able to remain in the community. DATA SOURCES AND STUDY
      SETTING: In-person and telephone interviews with 25 elderly individuals who
      applied for but did not enroll in Connecticut's Home Care Program for Elders
      (CHCPE). All met the state's nursing home level-of-care criteria. STUDY, DESIGN:
      In-depth discussions with a small, purposefully selected sample of functionally
      impaired elderly persons in the community. PRINCIPLE FINDINGS: Many sample
      members with very high levels of impairment and multiple chronic health
      conditions remained in the community without CHCPE services because of Medicare
      home health services combined with extensive levels of informal care. Some sample
      members, particularly those with more limited informal care networks, did not
      receive the level of care that they needed. Virtually all were at high risk for
      medical complications, hospitalizations for acute illnesses, falls, and further
      loss of functioning. Further, in many cases, informal care networks were
      overextended, stressed and vulnerable to break down. All but a few of those we
      interviewed were not receiving services through the waiver program for financial
      reasons. Most met Medicaid's income criteria but had assets that exceeded
      Medicaid's $2,000 limit. Several were not participating due to concerns about
      estate recovery. CONCLUSIONS: Additional formal help is needed to avoid eventual
      nursing home placement for many sample members. This could be achieved by
      expanding the availability of case management services and/or relaxing program
      financial requirements. Further, efforts to reduce Medicare home health
      expenditures must recognize the heightened vulnerability of many beneficiaries
      for potentially costly adverse outcomes.

PMID- 12068968
TI  - Mechanisms regulating the copy numbers of six LTR retrotransposons in the genome
      of Drosophila melanogaster.
AB  - There has been debate over the mechanisms that control the copy number of
      transposable elements in the genome of Drosophila melanogaster. Target sites in
      D. melanogaster populations are occupied at low frequencies, suggesting that
      there is some form of selection acting against transposable elements. Three main
      theories have been proposed to explain how selection acts against transposable
      elements: insertions of a copy of a transposable element are selected against;
      chromosomal rearrangements caused by ectopic exchange between element copies are
      selected against; or the process of transposition itself is selected against. The
      three theories give different predictions for the pattern of transposable element
      insertions in the chromosomes of D. melanogaster. We analysed the abundance of
      six LTR (long terminal repeat) retrotransposons on the X and fourth chromosomes
      of multiple strains of D. melanogaster, which we compare with the predictions of
      each theory. The data suggest that no one theory can account for the insertion
      patterns of all six retrotransposons. Comparing our results with earlier work
      using these transposable element families, we find a significant correlation
      between studies in the particular model of copy number regulation supported by
      the proportion of elements on the X for the different transposable element
      families. This suggests that different retrotransposon families are regulated by
      different mechanisms.

PMID- 12068969
TI  - Identification of a multicopy chromatin boundary element at the borders of
      silenced chromosomal domains.
AB  - The insulating properties required to delimit higher-order chromosomal domains
      have been shown to be shared by a variety of chromatin boundary elements (BEs).
      Boundary elements have been described in several species, from yeast to human,
      and we have previously reported the existence of a class of chromatin BEs in
      Drosophila melanogaster whose insulating activity requires the DNA-binding
      protein BEAF (boundary element-associated factor). Here we focus on the
      characterization of a moderately repeated 1.2 kb DNA sequence that encompasses
      boundary element 28 (BE28). We show that it directionally blocks
      enhancer/promoter communication in transgenic flies. This sequence contains a
      BEAF-binding sequence juxtaposed to an AT-rich sequence that harbors a strong
      nuclease-hypersensitive site. Using a combination of DNA-protein and protein
      blotting techniques, we found that this region is recognized by the A+T-binding
      D1 non-histone chromosomal protein of D. melanogaster, and we provide evidence
      that D1 and BEAF physically interact. In addition, the multicopy BE28 element
      maps to pericentric regions of the D. melanogaster 2L, 2R and X chromosome arms
      to which D1 has been shown to localize. In yeast, BEs that mark the periphery of
      silenced chromosomal domains have recently been shown to block the spreading of
      heterochromatin assembly. We propose that the BE28 repeat clusters could fulfill
      a similar function, acting as a local boundary between hetero- and euchromatin in
      a process involving interactions between the BEAF and D1 proteins.

PMID- 12068970
TI  - Telomere terminating with centromere-specific repeats is closely associated with
      a transposon derived gene in Chironomus pallidivittatus.
AB  - We provide evidence that centromere-specific 155 bp DNA repeats terminate one
      pair of telomeres at the telocentric, left end of the short fourth chromosome in
      Chironomus pallidivittatus. Earlier evidence indicated that all other telomeres
      are terminated by 340 bp telomere-specific repeats. DNA that borders the 155 bp
      repeat contains a transcriptionally active 396 codon open reading frame (ORF) a
      few kilobases away from the repeat array. The conceptual product of the ORF has
      regions with similarities to transposase, DNA binding and endonuclease motifs and
      is likely to have an evolutionary origin in a transposon. It is flanked, within
      degenerate inverted repeats, by a modified form of an element, Cp80, that has
      previously been found to insert only into 155 bp repeats and that contains a
      putative CENP-B box and a region that is prone to recombine. The ORF may
      therefore have a functional relation to the centromeric region.

PMID- 12068972
TI  - Trends in site-number change of rDNA loci during polyploid evolution in
      Sanguisorba (Rosaceae).
AB  - To elucidate the evolutionary dynamics of rDNA site number in polyploid plants,
      we determined 5S and 18S-5.8S-26S rDNA sites for ten species of Sanguisorba
      (2n=14, 28, 56) and a single species of each of three outgroup genera, Agrimonia
      (2n=28), Rosa (2n=14), and Rubus (2n=14) by the fluorescence in situ
      hybridization (FISH) method. We also estimated phylogenetic relationships among
      these species using matK chloroplast DNA (cpDNA) sequences, and reconstructed the
      evolutionary history of rDNA site number based on the maximum parsimony method.
      The 2n=14 and 2n=28 plants of all genera except Rosa carried two 5S rDNA sites,
      whereas Rosa and 2n=56 plants carried four sites. The 2n=14 plants had two 18S
      5.8S-26S rDNA sites, whereas Sanguisorba annua and 2n=28 plants had four or six
      sites. Phylogenetic analysis showed that polyploidization from 2n=14 to 2n=28 has
      occurred once or three times in Sanguisorba and Agrimonia. The 5S rDNA sites
      duplicated during each ancestral polyploidization were evidently lost after each
      polyploidization. However, the duplicated 18S-5.8S-26S rDNA sites were all
      conserved after each polyploidization. Thus, the duplicated 5S rDNA sites tend to
      have been eliminated, whereas those of 18S-5.8S-26S rDNA tend to have been
      conserved in Sanguisorba. In the most parsimonious hypothesis, 2n=14 in S. annua
      is a secondary, putatively dysploid state, reduced from 2n=28.

PMID- 12068971
TI  - Intranuclear relocation of the Plc beta3 sequence in cerebellar purkinje neurons:
      temporal association with de novo expression during development.
AB  - Interphase nuclei exhibit a cell type-specific topology of chromatin domains.
      This topology has been proposed to be established at a specific developmental
      stage and to be associated, in turn, with cell type-specific gene expression.
      Using murine, cerebellar Purkinje neurons, we have shown previously that the
      number and the extent of clustering as well as the spatial, intranuclear
      distribution of centromeric domains change as a function of postnatal
      development. Specifically, the redistribution of centromeric domains was
      determined to be associated temporally with major changes in gene expression.
      Given that centromeric sequences are not transcribed, we tested the hypothesis
      that the de novo expression of a specific sequence is similarly associated with a
      change in its spatial, intranuclear position. In Purkinje neurons, Plc beta3 is
      expressed de novo between postnatal day 2 and 7. In contrast, the level of
      expression of Rora remains constant throughout development, following its initial
      expression at embryonic day 15. Plc beta3 and Rora were labeled by fluorescence
      in situ hybridization within intact nuclei and their intranuclear, spatial
      positions quantified by confocal microscopy. When analyzed as the distance from
      the nuclear centroid, the mean fraction of radial distance of Plc beta3 signals
      changed from 57.3%+/-2.35 (+/-SEM) (n=50) at P3 to 37.9%+/-2.35 (n=50) at P5. In
      contrast, the mean fraction of the radial distance of Rora signals did not change
      during postnatal development, remaining at a mean of 60.1%+/-2.01 (n=208) from
      the nuclear centroid. While the results do not support a causal relationship
      between the spatial relocation of Plc beta3 and its de novo expression, their
      temporal association, as described herein, may be taken to support the hypothesis
      that its intranuclear, spatial positioning may represent one level of
      transcriptional control.

PMID- 12068973
TI  - Coiled bodies in nuclei from plant cells evolving from dormancy to proliferation.
AB  - To characterise the coiled bodies in meristematic nuclei of Saccharum
      officinarum, immunofluorescence labelling with antibodies against components of
      the splicing (U2B'' and Sm core protein B) and pre-rRNA processing (fibrillarin)
      complexes was used in cells from the dormant root primordia and from roots at
      different times after activation to the steady state of proliferation. The
      number, size and distribution of coiled bodies varied in the meristematic tissue
      depending on cell activity. While G0 cells in the dry primordia and proliferating
      cells showed a similar number of coiled bodies attached to their nucleoli, the
      number of nucleoplasmic coiled bodies greatly increased after the primordia were
      stimulated to proliferate. Their number remained steady from the time the
      meristematic population reached the steady state of proliferation, as estimated
      by flow cytometry. Fractionation studies demonstrated that coiled bodies are a
      part of the underlying nuclear matrix. Comparison of immunocytochemical and
      cytochemical data from confocal and electron microscopical studies demonstrated
      that the nucleolar and nucleoplasmic coiled bodies detected by confocal
      microscopy shared many features, suggesting that they form a family of closely
      related structures.

PMID- 12068975
TI  - Pleural thickening, trapped lung, and chronic empyema as sequelae of tuberculous
      pleural effusion: don't sweat the pleural thickening.

PMID- 12068974
TI  - Computerized automated morphometric assay including frequency estimation of
      pentachlorophenol induced nuclear anomalies (micronucleus) in catfish
      Heteropneustes fossilis.
AB  - An in vivo study of the effects of pentachlorophenol was carried out with a pre
      acclimatized fish species, Heteropneustes fossilis, using four sub-lethal
      concentrations, 0.1, 0.2, 0.3 and 0.4 ppm, and three sampling times, 48, 72 and
      96 h. Cytogenetic preparations were stained by the haematoxylin-eosin technique.
      The incidence of micronuclei was scored by a manual and an automated method.
      Small-sized micronuclei appeared in the cytoplasm in addition to the main
      nucleus. The frequency of micronucleated erythrocytes peaked at 4 days (96 h)
      exposure. The percentage of single micronuclei increased with longer exposures.
      The Mann-Whitney U test showed all micronuclei frequencies were significantly
      different from control (P<0.05). No statistical difference was observed between
      scores obtained by the manual and automated methods. A linear relationship
      between the percentage of micronucleated erythrocytes and dose was confirmed at
      all levels. Computer image analysis of morphological variations of erythrocytes
      indicated a 1:5 ratio of micronuclei and main nucleus accompanied by a reduction
      in cell volume by 600 dot units. Pentachlorophenol-mediated genotoxicity was
      confirmed in this fish for the first time. Possible consequences of genotoxicity
      and cytotoxicity are discussed.

PMID- 12068976
TI  - Epidemiology of tuberculosis in Kuwait from 1965 to 1999.
AB  - BACKGROUND: After several decades of continuous decline, the incidence of
      tuberculosis (TB) has increased over the last 10 years in several regions of the
      world. No reports have been published describing the epidemiology of TB in
      Kuwait. OBJECTIVES: To examine the trend of TB in Kuwait from 1965 to 1999 and
      analyse the factors associated with this trend. METHODS: Annual reports of the
      Kuwait central TB unit were examined. Tuberculosis registers recommended by the
      World Health Organization (WHO) and the International Union Against Tuberculosis
      and Lung Disease (IUATLD), which were available for the years 1998 and 1999, were
      also examined. RESULTS: The notification rate of TB for the whole population has
      declined from 259 per 100000 in 1965 to 24/100000 in 1999. There has been a
      steeper decline among Kuwaiti nationals, from 355/100 000 in 1965 to 14/100000 in
      1999. The average annual rate of decline in all cases of TB among Kuwaiti
      nationals was 11.9% from 1965 to 1976, and 11.0% from 1976 to 1989, but there was
      a slight rise of 4.3% per year from 1989 to 1999. The average annual rate of
      decline in all cases of TB among non-nationals was 6.3% from 1965 to 1976, and
      8.3% from 1976 to 1989, but there was a rise of 2.3% per year from 1989 to 1999.
      CONCLUSION: Tuberculosis in Kuwait declined steadily from 1965 to 1989. Since
      1989 there has been a slight rise in TB incidence in Kuwait among both Kuwaiti
      nationals and non-nationals.

PMID- 12068977
TI  - Patients hospitalised in Bolivia with pulmonary tuberculosis: risk factors for
      dying.
AB  - SETTING: The adult tuberculosis ward of a public hospital in the city of Santa
      Cruz, Bolivia. OBJECTIVES: To identify risk factors for dying among adult
      patients hospitalised with pulmonary tuberculosis. DESIGN: Hospital-based cross
      sectional study of patients admitted consecutively with pulmonary tuberculosis
      during the period November 1993-February 1996. RESULTS: A total of 466 patients
      were admitted to the study. There were 305 (65%) males, and the mean age was
      33.1. Seventy-five patients (16%) died during hospitalisation. Multiple logistic
      regression analysis identified the following predicting variables for death:
      associated pathology (odds ratio [OR] 2.88; 95% confidence interval [CI] 1.48
      5.36), female sex (OR 2.08; 95%CI 1.23-3.52), and number of lobes affected (OR
      1.48; 95%CI 1.23-1.79). CONCLUSIONS: These three variables predicting death allow
      us to identify patients with a diagnosis of pulmonary tuberculosis who should
      have priority for receiving hospital care. In Bolivia, physicians faced with a
      shortage of hospital beds should determine the presence or absence of this group
      of variables when evaluating patients for possible admission.

PMID- 12068978
TI  - A flare-up of tuberculosis due to war in Congo Brazzaville.
AB  - Congo Brazzaville, a country with a population of 3 million, experienced a period
      of war from 1997 to 1999. Before this time the annual increase in numbers of
      tuberculosis cases was on average 20%; in 2000 it was 84%. This situation had a
      considerable impact on the activities of the National Tuberculosis Programme.
      Before the war the diagnostic and treatment centres had notified nearly 100% of
      new cases of tuberculosis; in 2000 this had dropped to 76.19%, whereas the number
      of tuberculosis patients had almost doubled, from 5125 in 1999 to 9436 in 2000.
      New cases of smear-positive pulmonary tuberculosis represent 45% of cases, in
      comparison with an average of 55% before the war, and extrapulmonary tuberculosis
      30% versus 21% before the war. The relapse rate has not changed significantly, by
      approximately 2%, while the default rate has risen significantly, from 20% to
      about 26%. The rates of new smear-positive tuberculosis cases who are cured or
      have completed treatment remain unchanged (70%), while the mortality rate dropped
      after the war from 6% to 1.23%. The war led to an increase in rates of
      tuberculosis, particularly in the two main cities, Brazzaville and Pointe-Noire,
      to which refugees had fled from the rural areas. This resulted in an excessive
      workload for the health workers. Sustained financial support is needed to reduce
      tuberculosis transmission in the Congo population.

PMID- 12068979
TI  - Surveillance of drug resistance in tuberculosis in two districts of South India.
AB  - SETTING: Tuberculosis Research Centre, Chennai, India. OBJECTIVES: To determine
      the levels of drug resistance in new and previously treated cases of pulmonary
      tuberculosis in the composite districts of North Arcot (Tamil Nadu State) and
      Raichur (Karnataka State) in South India. DESIGN: Two specimens of sputum from
      320 patients attending 23 participating centres in North Arcot district and 314
      patients from 20 participating centres in Raichur district were tested for drug
      susceptibility to isoniazid (H), rifampicin (R), ethambutol (E), streptomycin (S)
      and ofloxacin (O). The studies were undertaken using the guidelines prescribed by
      the WHO/IUATLD Working Group on Anti-tuberculosis Drug Resistance Surveillance.
      RESULTS: In North Arcot district, resistance to any drug tested was found in
      27.7% of new cases; any H resistance in 23.4%, any R resistance in 2.8% and
      multidrug resistance (resistance to at least H and R: MDR) in 2.8%. In previously
      treated cases, resistance to any drug was observed in 81.2%, and any resistance
      to H, R and HR in 81%, 69% and 69%, respectively. In Raichur district, resistance
      to any drug was observed in 21.9% of new cases; any resistance to H, R and HR
      (MDR) was found in 18.7%, 2.5% and 2.5%, respectively. All previously treated
      patients were resistant to H and R (100%). CONCLUSION: In North Arcot district,
      the proportion of MDR-TB in newly diagnosed patients has marginally increased
      over the last 10-15 years, whereas it has remained fairly constant in Raichur
      district. An increase in resistance was noted in previously treated cases in both
      districts, although the numbers of patients are small.

PMID- 12068980
TI  - Tuberculosis transmission and the impact of intervention on the incidence of
      infection.
AB  - SETTING: England and Wales. OBJECTIVE: To quantify the relative contribution of
      vaccination, chemotherapy and preventive therapy to the reduction in tuberculosis
      incidence in England and Wales between 1953 and 1990. DESIGN: A compartmental
      model of tuberculosis transmission was fitted to notification data between 1913
      and 1939 to estimate pre-vaccination parameters. Best-fit estimates of the rates
      of chemotherapy and preventive therapy were derived by fitting the model to
      notification data between 1953 and 1990. Published vaccination rates were used.
      MAIN OUTCOME MEASURE: Number of cases of pulmonary tuberculosis averted. RESULTS:
      The numbers of respiratory tuberculosis cases averted between 1953 and 1990 by
      the use of preventive therapy, vaccination and chemotherapy were 288318, 57085
      and 206996, respectively. CONCLUSIONS: Of those interventions considered,
      preventive therapy has the greatest impact on transmission. The duration of
      infectiousness is long, with an onset that is likely to pre-date sputum
      positivity.

PMID- 12068981
TI  - Predominant VNTR family of strains of Mycobacterium tuberculosis isolated from
      South Asian patients.
AB  - SETTING: Despite the low incidence of tuberculosis in the UK, some minority
      ethnic groups, particularly those originating from South Asia, experience very
      high incidence rates. OBJECTIVE: Comparison of the variable number tandem repeat
      (VNTR) profiles of strains of Mycobacterium tuberculosis circulating in an
      immigrant community in the UK with those found in the country of ethnic origin.
      DESIGN: Isolates of M. tuberculosis were collected from samples obtained from
      patients attending clinics in Leeds and Bradford, UK and Rawalpindi, Pakistan.
      Strains were compared using VNTR analysis and mixed-linker PCR. RESULTS:
      Comparison of VNTR profiles found that one profile (42235) represented 37% of
      patient isolates from Rawalpindi and 23% of patient isolates in Leeds and
      Bradford, where it was associated exclusively with patients with South Asian
      names. A second profile (02235) represented 15% of patient isolates in Leeds and
      Bradford, and was also exclusively associated with the South Asian community.
      These profiles could be subdivided by mixed-linker PCR analysis. CONCLUSION: The
      VNTR profile 42235 may represent a family of strains commonly found in
      communities associated with South Asia.

PMID- 12068982
TI  - Low plasma concentrations of rifampicin in tuberculosis patients in Indonesia.
AB  - SETTING: Although rifampicin is a key drug in tuberculosis treatment, little is
      known about its quality and bioavailability in countries endemic for
      tuberculosis. High drug levels may lead to increased toxicity, while low drug
      levels may predispose to treatment failure and relapse. OBJECTIVE: To investigate
      possible variations in the bioavailability of plasma rifampicin in tuberculosis
      patients in Indonesia. DESIGN: Plasma concentrations of rifampicin and the
      rifampicin content of drug formulations in use were measured among 62 non
      selected tuberculosis patients in Jakarta, Indonesia. RESULTS: Plasma
      concentrations of rifampin were generally low: 70% of patients had 2-hour plasma
      concentrations (Cmax) below 4 mg/L. No toxic plasma concentrations of rifampicin
      (>20 mg/L) were found. The strongest predictive factor for the magnitude of
      rifampicin concentrations was the drug manufacturer. The rifampicin content of
      the different drug preparations used was normal (90.5-103.6% of the reference
      standard). No association was found between low plasma rifampicin concentrations
      and delayed sputum conversion or treatment failure. CONCLUSION: The unexpectedly
      low plasma concentrations of rifampicin in this setting are most likely due to
      reduced bioavailability of local drug preparations, as the rifampicin content of
      the drug preparations was found to be normal. The clinical significance of these
      findings remains to be determined.

PMID- 12068983
TI  - Ofloxacin population pharmacokinetics in patients with tuberculosis.
AB  - SETTING: Two tuberculosis hospitals in the United States. OBJECTIVE: To determine
      the population pharmacokinetic (PK) parameters of ofloxacin following multiple
      oral doses. DESIGN: A total of 73 patients with tuberculosis (TB) participated in
      the study. Subjects received multiple doses of ofloxacin as part of their
      treatment. They also received concurrent medications based on in vitro
      susceptibility data. Serum samples were collected over 10 h and assayed by a
      validated high performance liquid chromatography (HPLC) assay. Concentration-time
      data were analyzed using population methods. RESULTS: Ofloxacin concentrations
      increased linearly with increasing oral doses. Delayed absorption was seen at
      least once in 29% of patients. Ofloxacin elimination decreased with declining
      renal function and increasing age. Higher daily doses were well tolerated, and
      appeared to maximize the peak concentration to minimal inhibitory concentration
      ratio (Cmax:MIC). CONCLUSION: Ofloxacin PK parameters were comparable to those
      previously published for other patient populations. Higher daily doses may offer
      pharmacodynamic advantages for the treatment of TB.

PMID- 12068984
TI  - Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis
      patients.
AB  - SETTING: Transforming growth factor-beta (TGF-beta) plays an important role in
      many diseases, influencing as it does such processes as immune responses,
      fibrosing processes, and angiogenesis. Recently, polymorphisms have been
      described for TGF-beta that are associated with the risk of several diseases. In
      this study, we investigated whether TGF-beta 1 polymorphism has an effect on
      sarcoidosis and tuberculosis. OBJECTIVE: TGF-beta 1 Codon 10 T869C polymorphism
      was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and
      101 tuberculosis patients. DESIGN: The TGF-beta genotype was determined using
      polymerase chain reaction restriction fragment length polymorphism. RESULTS: We
      found no significant differences in TGF-beta genotypes between sarcoidosis
      patients and healthy controls or tuberculosis patients and controls. The long
      axis of the tuberculin skin test was larger in the CC type compared with the CT
      type. However, there was no association between the TGF-beta genotype and the
      roentgenographic stage, the disappearance of shadows, or organ involvement in
      sarcoidosis, nor any association between genotype, the extent or type of
      roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis.
      CONCLUSION: From the results, we believe that TGF-beta polymorphisms on the whole
      do not have a strong influence on disease onset or clinical progression in
      sarcoidosis and tuberculosis, although this polymorphism might have an effect on
      the immune response in a tuberculosis host.

PMID- 12068985
TI  - The effect of pleural fluid content on the development of pleural thickness.
AB  - SETTING: Residual pleural thickness (RPT) is a common complication of tuberculous
      pleurisy (TP), and the degree of RPT cannot be predicted in advance. OBJECTIVES:
      To determine whether pleural fluid content has an effect on the development of
      RPT. DESIGN: Forty-seven patients with TP were enrolled in the study. A set of
      biochemical tests: lactate dehydrogenase, glucose, total proteins, adenosine
      deaminase, tumour necrosis factor alpha (TNF-alpha), alpha-1 acid glycoprotein
      (AAG), alpha-2 macroglobulin, C-reactive protein (CRP), complement 3 and
      complement 4 were studied in the pleural fluid samples. After 6 months of anti
      tuberculosis treatment, patients were re-evaluated for RPT. RPT was defined in a
      posteroanterior chest radiograph as a pleural space of >2 mm or >10 mm measured
      in the lower lateral chest at the level of an imaginary horizontal line
      intersecting the diaphragmatic dome. RESULTS: Seventeen patients (36.17%) had an
      RPT of <2 mm, 18 (38.29%) had an RPT of 2-10 mm, and 12 (25.53%) had an RPT of
      >10 mm. TNF-alpha levels were lower in patients with an RPT of <2 mm than in
      patients with an RPT of 2-10 mm or >10 mm (P < 0.05 and P < 0.01, respectively).
      The level of TNF-alpha was higher in patients with an RPT of >10 mm compared to
      the 2-10 mm group (P < 0.05). Meanwhile, pleural fluid glucose, AAG and CRP
      concentrations were significantly higher in patients with an RPT of >10 mm than
      in patients with <2 mm RPT (P < 0.05, P < 0.01, and P < 0.05, respectively).
      CONCLUSION: In TP, the development and degree of RPT are significantly correlated
      to the glucose, CRP, AAG, and TNF-alpha levels in the pleural fluid.

PMID- 12068986
TI  - Rapid indication of multidrug-resistant tuberculosis from liquid cultures using
      FASTPlaqueTB-RIF, a manual phage-based test.
AB  - SETTING: A Mycobacteriology Reference Laboratory in Johannesburg, South Africa.
      OBJECTIVE: To determine the ability of FASTPlaqueTB-RIF, a rapid bacteriophage
      based test, to correctly identify rifampicin susceptibility in clinical strains
      of Mycobacterium tuberculosis after growth in the Bactec 460 semi-automated
      liquid culture system. DESIGN: A comparative study of FASTPlaqueTB-RIF and
      conventional drug susceptibility methods, with selection bias to include
      sufficient rifampicin-resistant strains. RESULTS: Rifampicin susceptibility
      results were available for 133 strains of M. tuberculosis. Using the Bactec 460
      method, 42 of these strains were rifampicin-resistant and 91 strains were
      rifampicin-susceptible. A further one strain was found to have a mutation in the
      rpoB gene which was strongly indicative of rifampicin resistance. Sensitivity,
      specificity and overall accuracy for the FASTPlaqueTB-RIF were respectively 100%,
      98.8% and 99.2% for detection of rifampicin resistance; 95.3% (41/43) of the
      rifampicin-resistant strains were also resistant to isoniazid (multidrug
      resistant). CONCLUSION: FASTPlaqueTB-RIF offers performance comparable to the
      Bactec 460 method, with results available within 2 days and without the need for
      specialised equipment. This makes FASTPlaqueTB-RIF a rapid test for rifampicin
      resistance suitable for widespread application. A combination of the FAST
      PlaqueTB-RIF test with semi-automated liquid culture reduces the time required to
      report susceptibility results, enabling rapid and appropriate management of
      patients with MDR-TB. Rifampicin resistance was a good predictor of multidrug
      resistance in this population.

PMID- 12068987
TI  - Performance of a rapid phage-based test, FASTPlaqueTB, to diagnose pulmonary
      tuberculosis from sputum specimens in South Africa.
AB  - SETTING: Twelve primary health care clinics in the South Peninsula
      Administration, Cape Town, Western Cape Province, South Africa. OBJECTIVE: To
      evaluate the performance of FAST-PlaqueTB, a new phage-based test, for the rapid
      diagnosis of TB in individuals with no previous history of TB treatment
      presenting at primary health care clinics in Cape Town, South Africa. DESIGN: A
      comparative study of FASTPlaqueTB, auramine smear microscopy and Lowenstein
      Jensen culture of 1692 decontaminated sputum specimens from 853 patients
      suspected of having TB. Resolution of discrepant results was undertaken by review
      of clinical information, chest X-ray and follow-up of treatment outcomes.
      RESULTS: FASTPlaqueTB detected TB in 75.2% of culture-confirmed cases and 70.3%
      of all cases with a clinical diagnosis of TB, with a specificity of 98.7% and
      99.0%, respectively. The performance parameters of FASTPlaqueTB were
      significantly superior to those of concentrated auramine smear microscopy (63.4%
      and 61.3% sensitivity, and 97.4% and 97.3% specificity in culture-confirmed and
      all cases, respectively). Of those patients with two negative sputum smears, FAST
      PlaqueTB detected TB in 54.1% of TB cases confirmed by culture and 48.8% of all
      cases with a clinical diagnosis of TB. A combination of smear microscopy and
      FASTPlaqueTB enabled 81.2% of culture-confirmed cases and 78.4% of total TB cases
      to be detected within 2 days of presentation. CONCLUSION: FASTPlaqueTBTM is a
      rapid, manual test for the diagnosis of TB. The test has significantly higher
      sensitivity overall compared with auramine sputum smear microscopy in individuals
      with no previous history of TB treatment, although smear microscopy did detect
      the most infectious of the TB cases. The FAST-PlaqueTB test is easy to perform,
      requires no dedicated equipment, and results are read by eye within 48 hours.
      This test can be useful for the diagnosis of TB in developing countries with a
      high burden of TB where other rapid diagnostic tests may not be appropriate. The
      test shows promising performance, particularly in the diagnosis of smear-negative
      disease, and could be used in conjunction with smear microscopy to aid in the
      diagnosis of additional cases of TB.

PMID- 12068988
TI  - Evaluation of an amplified Mycobacterium tuberculosis direct test in clinical
      specimens.
AB  - SETTING: An increase in tuberculosis cases has been observed since the last
      decade, and rapid and specific tests are needed to directly detect Mycobacterium
      tuberculosis in respiratory specimens. The Amplified Mycobacterium Tuberculosis
      Direct Test (AMTDT) is a direct specimen assay for the identification of M.
      tuberculosis. OBJECTIVE: To evaluate the sensitivity and specificity of the
      AMTDT. METHODS: We performed the test in 426 patients: 58 patients who had
      culture-proven and/or clinically diagnosed tuberculosis, and 368 patients who
      were negative for M. tuberculosis by culture and clinical criteria (the control
      group). The results were compared to culture and clinical diagnosis of
      tuberculosis. RESULTS: AMTDT was found to be positive in 35 of the 58 patients
      who had culture-proven and/or clinically diagnosed tuberculosis and 71 of the 368
      controls. Seventeen of the tuberculosis group were smear-negative, and AMTDT was
      positive in 11 of these patients. The sensitivity and specificity of the test
      were respectively 60% and 80%. CONCLUSION: AMTDT can be used as a complementary
      technique in tuberculosis patients in the presence of high clinical suspicion.

PMID- 12068989
TI  - Association of willingness to pay with severity of chronic obstructive pulmonary
      disease, health status and other preference measures.
AB  - SETTING: Willingness to pay (WTP) is a method frequently used to measure the
      benefits of health interventions in monetary terms. OBJECTIVE: To assess the
      construct validity of the WTP method in patients with chronic obstructive
      pulmonary disease (COPD). DESIGN: Fifty-nine COPD patients (34 men, mean age 57
      years) were asked about their maximum WTP for a theoretical cure for COPD. In
      addition, they reported utility scores using standard gamble, time trade-off, a
      multi-attribute utility instrument, and a rating scale. They also responded to
      the Short Form 36 (SF-36) questionnaire, dyspnea measures and had comprehensive
      pulmonary function tests. RESULTS: The participants reported a median WTP of
      Norwegian kroner 200 000 (US $24 096) for a theoretical cure for COPD without
      side-effects. The associations of WTP with utility scores, dimensions of health
      status, dyspnea measures and lung function tests were low. CONCLUSION: The
      findings of this study question the validity of the WTP method in patients with
      chronic obstructive pulmonary disease.

PMID- 12068990
TI  - An investigation of suspected exogenous reinfection in tuberculosis patients in
      Kampala, Uganda.
AB  - Exogenous reinfection with Mycobacterium tuberculosis is an important phenomenon
      that occurs with unknown frequency in both immunocompromised and immunocompetent
      persons. As previous investigations suggest that exogenous reinfection can occur
      in both of these populations, we reviewed data for 40 cases of suspected TB
      relapse in an attempt to determine the frequency of this phenomenon in patients
      treated at the TB Research Unit in Kampala, Uganda. Our findings suggest that
      while this entity can occur in immunocompetent persons, immunocompromised persons
      are probably at higher risk for exogenous reinfection with M. tuberculosis.

PMID- 12068991
TI  - Knowledge and practice pattern of non-allopathic indigenous medical practitioners
      regarding tuberculosis in a rural area of India.
AB  - OBJECTIVE: To assess the knowledge and practice patterns of non-allopathic
      indigenous medical practitioners (IMPs) regarding tuberculosis (TB). METHODS:
      Seventy-four IMPs practising in Naraingarh block, a rural area of Haryana State,
      India, were interviewed using a semi-structured interview schedule. RESULTS:
      Fifty-four per cent (40/74) of the IMPs saw two to five TB patients every month.
      Sixty-one per cent (46/74) reported that they based their diagnosis of TB on
      symptoms alone, whereas 38% use diagnostic tests such as chest X-ray, erythrocyte
      sedimentation rate and sputum examination. Forty per cent of the IMPs reported
      that alcohol was the cause of TB, 36.5% cited smoking and 17.6% reported
      infection as the cause. Only 34% (25/74) of IMPs reported that they treated TB
      patients, while the rest said that they referred such cases to nearby hospitals.
      Anti-tuberculosis drugs used by IMPs were isoniazid, rifampicin and streptomycin,
      but none of them knew the dosage of the drugs, the duration of treatment or the
      correct regimen. Sixty-four per cent of the 25 IMPs reported using ayurvedic
      medicines. CONCLUSION: Considerable proportions of TB patients seek IMPs for cure
      of TB, while the knowledge and practice of IMPs is inadequate.

PMID- 12068992
TI  - Architectural programming for the workplace and the careplace.
AB  - Sensitive planning and architectural design will impact long-term costs and daily
      operations. At the same time, the quality of the total environment has a direct
      impact on the patient, the family and the staff. These needs should be carefully
      balanced with the emotions of the patient, the care partner (parent, husband,
      wife or guardian) and those of the clinical team (physicians, nurses and staff).
      This article addresses the first step in the process; the master plan and then
      focuses in detail on one aspect of the architectural work referred to as
      architectural programming. The key to the process is selecting the best team of
      consultants, following the steps carefully, involving the client at every
      appropriate milestone along the way and asking the right questions. With this
      experienced team on board; following the proper steps, listening carefully to the
      answers and observing the daily process one can expect a successful product.

PMID- 12068993
TI  - Clinical program leadership: skill requirements for contemporary leaders.
AB  - With knowledge of these leadership requirements and a shrinking base of
      experienced managers, healthcare organizations and professional societies have
      little choice in their approach to prepare for the leadership development
      challenges of the future. Organizations will focus leadership development,
      training, and continuing management education on integrating business tools and
      skills into clinical program management. The management requirements for clinical
      programs will continue to grow in complexity and the number of qualified managers
      will continue to diminish, New approaches to solving this shortage will evolve.
      Professional, forprofit companies, healthcare provider organizations, and
      academic programs will develop clinical program management training tracks.
      Organizations that create solutions to this management imperative will maintain
      their competitive edge in the challenging times that will greet the industry in
      the future.

PMID- 12068994
TI  - Intensity modulated radiation therapy--the shape of things to come?
AB  - Over the past century, the field of radiation oncology has seen tremendous
      technological advances. Some of these advances relate to biomedical
      accomplishments, while many are directly related to those achieved in computing
      and information technology. For example, developments in radiation treatment
      planning systems are intimately connected to progress in all of computing, and
      have culminated in the ability of radiation oncologists to accurately plan even
      the most complex therapy. Treatment machines, themselves tooled with embedded
      computer chips and processors, have evolved from rigid monstrosities to highly
      flexible, compact, machines capable of moving with robotic-like precision. The
      addition of multi-leaf collimators to these treatment machines has added yet
      another dimension to the picture. The ability to coordinate the fine motor
      movements of these collimators along with the coarser movements of the machine
      itself has required a level of control not possible manually. Computers again
      have provided a solution, and the result was not just a new means of directing
      the radiation beam, but a revolution in how radiation itself was delivered
      Intensity Modulated Radiation Therapy. Now, Intensity Modulated Radiation Therapy
      (IMRT) is practiced in hundreds of radiation oncology departments worldwide. The
      administration process, which challenges the most sophisticated computer planning
      and treatment control systems, requires not just proficient technical support,
      but also a dedicated administrative infrastructure. The payoff, however, promises
      to be big. Preliminary clinical outcome reports suggest that significant
      reductions in toxicity will be achievable, making increased control rates more
      likely. In addition, favorable CMS reimbursement changes make it probable that
      the technology will spread rapidly throughout the radiation oncology community.
      Studies are ongoing to help identify the most appropriate use of the therapy.
      Ultimately, IMRT is likely to become a readily available treatment for use in
      select cases.

PMID- 12068995
TI  - Clarifying today's coding and compliance issues. The more things change....

PMID- 12068996
TI  - Direct magnitude estimates of speech intelligibility in dysarthria: effects of a
      chosen standard.
AB  - Direct magnitude estimation (DME) has been used frequently as a perceptual
      scaling technique in studies of the speech intelligibility of persons with speech
      disorders. The technique is typically used with a standard, or reference
      stimulus, chosen as a good exemplar of "midrange" intelligibility. In several
      published studies, the standard has been chosen subjectively, usually on the
      basis of the expertise of the investigators. The current experiment demonstrates
      that a fixed set of sentence-level utterances, obtained from 4 individuals with
      dysarthria (2 with Parkinson disease, 2 with traumatic brain injury) as well as 3
      neurologically normal speakers, is scaled differently depending on the identity
      of the standard. Four different standards were used in the main experiment, three
      of which were judged qualitatively in two independent evaluations to be good
      exemplars of midrange intelligibility. Acoustic analyses did not reveal obvious
      differences between these four standards but suggested that the standard with the
      worst-scaled intelligibility had much poorer voice source characteristics
      compared to the other three standards. Results are discussed in terms of possible
      standardization of midrange intelligibility exemplars for DME experiments.

PMID- 12068997
TI  - Oropharyngeal swallow in younger and older women: videofluoroscopic analysis.
AB  - Much of the initial research on normal swallowing has been conducted in young
      men. Recently, there has been increasing interest in determining whether there
      are differences between the sexes in swallowing function and in the effects of
      aging on swallowing in both sexes. This investigation examined the swallowing
      ability of 8 healthy young women between the ages of 21 and 29 and 8 healthy
      older women between the ages of 80 and 93 during two swallows each of 1 ml and 10
      ml liquid boluses. Videofluoroscopic studies of these swallows were reviewed in
      slow motion and real time to confirm the absence of swallowing disorders.
      Kinematic analysis of each swallow was completed. Data on range of motion of
      pharyngeal structures and coordination characteristics of the oropharyngeal
      swallow were taken from this kinematic analysis. Position of the larynx at rest
      and length of neck were compared between the two groups. Data from this study
      were compared with previously published data on younger and older men.
      Interestingly, the range of motion of the older women was often greater than that
      of the young women. Only tongue base movement diminished significantly with age
      in women. Volume effects observed in duration and extent of movement during the 1
      ml and 10 ml swallows were similar to those in earlier studies. Older women also
      exhibited an increased range of motion relative to the old men. This increase may
      indicate a compensation for aging effects not seen in older men.

PMID- 12068998
TI  - Fundamental frequency onset and offset behavior: a comparative study of children
      and adults.
AB  - Short-term changes in vowel fundamental frequency (F0) immediately preceding (F0
      offset) and following (F0 onset) production of voiceless obstruents were examined
      in groups of 4-year-olds, 8-year-olds, and 21-year-olds. Definitive patterns of
      laryngeal behavior were observed for each measure F0 was found to significantly
      lower at vowel offset across age groups, with no significant differences noted
      between groups, suggesting that F0 offset is simply an acoustic consequence of
      producing a voiceless obstruent preceded by a vowel. The F0 at vowel onset was
      high and significantly decreased thereafter. Age-related differences were
      identified for F0 onset with 4-year-olds in that their F0 rose to a lesser degree
      than that of adults. However, adult females demonstrated a greater change in both
      F0 onset and F offset behavior than adult males and children, suggesting that age
      related differences in F0 behavior are likely to be influenced by sex. The
      results are discussed with regard to the physiologic constraints of F0
      surrounding voiceless obstruent production in children and adults.

PMID- 12068999
TI  - Kinematic strategies for hyoid movement in rapid sequential swallowing.
AB  - Past videofluoroscopic and EMG evidence has shown that rapid sequential
      swallowing differs from discrete swallows, but our knowledge of the control
      strategies remains incomplete. This study examined in detail the
      interrelationships among kinematic variables to discern the strategies for
      deglutitive hyoid motion during discrete (5 cc, 10 cc, 20 cc, 30 cc) and rapid
      sequential (120 cc) swallowing tasks. Submental ultrasound was conducted with
      head and transducer stabilization on 30 healthy subjects (15 males, 15 females)
      in three age groups (20-39, 40-59, 60-79 yrs). Frame-by-frame changes in hyoid
      position were tracked from digitized images of 236 discrete and 318 rapid
      sequential swallows. Repeated-measures analyses of variance were conducted on a
      number of kinematic variables with corrections for multiple tests and
      comparisons. The main effect of task was significant for all variables except
      forward peak velocity. Per post hoc contrasts, rapid sequential swallows had
      significantly reduced maximal amplitude (maximal displacement), total distance,
      backward peak velocity, at-max and total durations, and time to backward peak
      velocity in comparison with discrete swallows of any volume. Amplitude "down
      scaling" was the prominent kinematic strategy used to accomplish rapid sequential
      swallows in a shorter time while keeping forward peak velocity essentially
      unchanged. In contrast, amplitude "up-scaling" was the strategy for accommodating
      larger-volume discrete swallows. Our results confirm built-in flexibility in the
      functional range of deglutitive hyoid motion.

PMID- 12069000
TI  - Botox treatment in adductor spasmodic dysphonia: a meta-analysis.
AB  - Over the years many studies have been conducted to document the treatment effects
      of Botulinum toxin type A in adductor spasmodic dysphonia. The results of these
      studies have led to the view that overall Botulinum toxin treatment is moderately
      effective. This study reviews efficacy research qualitatively and quantitatively
      to determine the extent to which this conclusion is fully supported by the data.
      Although the data indicate moderate overall improvement as a result of Botulinum
      toxin treatment, they also suggest significant variation across patients,
      measurements, and treatment conditions. This result, together with methodological
      limitations and lack of standardization in BT efficacy research, justifies
      caution when making inferences regarding BT treatment benefit in adductor
      spasmodic dysphonia.

PMID- 12069001
TI  - Interaction of speech coders and atypical speech I: effects on speech
      intelligibility.
AB  - We investigated how standard speech coders, currently used in modern
      communication systems, affect the intelligibility of the speech of persons who
      have common speech and voice disorders. Three standardized speech coders (viz.,
      GSM 6.10 [RPE-LTP], FS1016 [CELP], FS1015 [LPC]) and two speech coders based on
      subband processing were evaluated for their performance. Coder effects were
      assessed by measuring the intelligibility of vowels and consonants both before
      and after processing by the speech coders. Native English talkers who had normal
      hearing identified these speech sounds. Results confirmed that (a) all coders
      reduce the intelligibility of spoken language; (b) these effects occur in a
      consistent manner, with the GSM and CELP coders providing the least degradation
      relative to the original unprocessed speech; and (c) coders interact with
      individual voices so that speech is degraded differentially for different
      talkers.

PMID- 12069002
TI  - Grammatical morphology and perception of synthetic and natural speech in children
      with specific language impairments.
AB  - Studies investigating the relationship between the use of inflectional morphology
      and speech-perception abilities in children with SLI traditionally have employed
      synthetic speech stimuli. The purpose of this study was to replicate the findings
      reported in Leonard, McGregor, and Allen (1992) with an older group of children
      with SLI and to determine if the pattern of deficits seen for synthetic speech
      extends to perception of natural speech stimuli. The speech-perception abilities
      of 27 children between the ages of 6;11 and 8;11 (15 SLI and 12 NL) were compared
      using natural and synthetic versions of the [das]-[daS], [dabiba]-[dabuba], and
      [i]-[u] contrast pairs originally used in Leonard et al. The findings reported by
      Leonard et al. were replicated with synthetic speech but not for the natural
      speech. Use of inflectional morphology in obligatory contexts by the children
      with SLI was not significantly correlated with their perception abilities for any
      of the natural or synthetic speech-contrast pairs. Further, although both groups'
      ability to maintain the target contrast in memory declined over the span of the
      trials for all target contrasts for both natural and synthetic speech, the rate
      of decline did not differ significantly between the SLI and NL groups. Findings
      are discussed with respect to possible deficits in linking phonological
      representations to grammatical representations in children with SLI.

PMID- 12069003
TI  - Methods for characterizing participants' nonmainstream dialect use in child
      language research.
AB  - Three different approaches to the characterization of research participants'
      nonmainstream dialect use can be found in the literature. They include listener
      judgment ratings, type-based counts of nonmainstream pattern use, and token-based
      counts. In this paper, we examined these three approaches, as well as shortcuts
      to these methods, using language samples from 93 children previously described in
      J. Oetting and J. McDonald (2001). Nonmainstream dialects represented in the
      samples included rural Louisiana versions of Southern White English (SWE) and
      Southern African American English (SAAE). Depending on the method and shortcut
      used, correct dialect classifications (SWE or SAAE) were made for 88% to 97% of
      the participants; however, regression algorithms had to be applied to the type-
      and token-based results to achieve these outcomes. For characterizing the rate at
      which the participants produced the nonmainstream patterns, the token-based
      methods were found to be superior to the others, but estimates from all
      approaches were moderately to highly correlated with each other. When type-
      and/or token-based methods were used to characterize participants' dialect type
      and rate, the number of patterns included in the analyses could be substantially
      reduced without significantly affecting the validity of the outcomes. These
      findings have important implications for future child language studies that are
      done within the context of dialect diversity.

PMID- 12069004
TI  - Speech segmentation by native and non-native speakers: the use of lexical,
      syntactic, and stress-pattern cues.
AB  - Varying degrees of plasticity in different subsystems of language have been
      demonstrated by studies showing that some aspects of language are processed
      similarly by native speakers and late-learners whereas other aspects are
      processed differently by the two groups. The study of speech segmentation
      provides a means by which the ability to process different types of linguistic
      information can be measured within the same task, because lexical, syntactic, and
      stress-pattern information can all indicate where one word ends and the next
      begins in continuous speech. In this study, native Japanese and native Spanish
      late-learners of English (as well as near-monolingual Japanese and Spanish
      speakers) were asked to determine whether specific sounds fell at the beginning
      or in the middle of words in English sentences. Similar to native English
      speakers, late-learners employed lexical information to perform the segmentation
      task. However, nonnative speakers did not use syntactic information to the same
      extent as native English speakers. Although both groups of late-learners of
      English used stress pattern as a segmentation cue, the extent to which this cue
      was relied upon depended on the stress-pattern characteristics of their native
      language. These findings support the hypothesis that learning a second language
      later in life has differential effects on subsystems within language.

PMID- 12069005
TI  - Verbal short-term memory in Down syndrome: a problem of memory, audition, or
      speech?
AB  - The current study explored three possible explanations of poor verbal short-term
      memory performance among individuals with Down syndrome in an attempt to
      determine whether the condition is associated with a fundamental verbal short
      term memory deficit. The short-term memory performance of a group of 19 children
      and young adults with Down syndrome was contrasted with that of two control
      groups matched for level of receptive vocabulary. The specificity of a deficit
      was assessed by comparing memory for verbal and visuo-spatial information. The
      effect of auditory problems on performance was examined by contrasting memory for
      auditorily presented material with that for material presented both auditorily
      and visually. The influence of speech-motor difficulties was investigated by
      employing both a traditional recall procedure and a serial recognition procedure
      that reduced spoken response demands. Results confirmed that individuals with
      Down syndrome do show impaired verbal short-term memory performance for their
      level of receptive vocabulary. The findings also indicated that this deficit is
      specific to memory for verbal information and is not primarily caused by auditory
      or speech-production difficulties.

PMID- 12069006
TI  - Listener comprehension of severely dysarthric speech: effects of linguistic cues
      and stimulus cohesion.
AB  - This study is the second in a two-part series examining the effects of linguistic
      variables on listener processing of dysarthric speech. The first study (see K. C.
      Hustad & D. R. Beukelman, 2001) examined the effects of experimentally imposed
      topic cues, alphabet cues, and combined cues along with a control condition in
      which no cues were provided on intelligibility of unrelated and related sentences
      produced by 4 women with severe dysorthria secondary to cerebral palsy. The
      present study examined the effects of these same variables on listener
      comprehension of severely dysarthric speech produced by the same speakers. In
      addition, the relationship between intelligibility and comprehension was examined
      for each cue and stimulus cohesion condition. Consistent with intelligibility
      results, the present study found that combined cues resulted in higher
      comprehension scores than any other cue condition and that no cues resulted in
      lower comprehension scores than any other cue condition for both related and
      unrelated sentences. In addition, comprehension scores were higher for alphabet
      cues than for topic cues in the related-sentences condition. Findings dissimilar
      from intelligibility results were as follows: (a) comprehension scores associated
      with alphabet and topic cues did not differ for unrelated sentences, and (b)
      comprehension scores were higher for related than for unrelated sentences in each
      cue condition. Finally, significant positive relationships between
      intelligibility and comprehension data were found only for topic cues in the
      unrelated-sentences condition and for alphabet cues in the related-sentences
      condition.

PMID- 12069007
TI  - Morehead & Ingram (1973) revisited.
AB  - The finding in Morehead and Ingram (1973) that children with a language
      impairment do better in the use of inflectional morphology than MLU-matched
      typically developing children has been in marked contrast to several subsequent
      studies that have found the opposite relationship (cf. review in Leonard, 1998).
      This research note presents a reanalysis of a subset of the original Morehead and
      Ingram data in an attempt to reconcile these contradictory findings. The
      reanalysis revealed that the advantage on inflectional morphology for children
      with language impairment was only on the progressive suffix, not on plural and
      possessive or on the verbal morphemes third-person present tense and past tense.
      The results of the reanalysis are in line with more recent research (e.g., Rice,
      Wexler, & Cleave, 1995). The resolution of these discrepant results highlights
      the critical roles that methodological issues play--specifically, how subjects
      are matched on MLU, how inflectional morphology is measured, and the selection of
      subjects with regard to age.

PMID- 12069008
TI  - Auditory training induces asymmetrical changes in cortical neural activity.
AB  - Pre-attentive cortical evoked potentials reflect training-induced changes in
      neural activity associated with speech-sound training. Seven normal-hearing young
      adults were trained to identify two synthetic speech variants of the syllable
      /ba/. As subjects learned to correctly identify the two stimuli, changes in P1,
      N1, and P2 amplitudes were observed. Of particular interest is that P1, N1, and
      P2 components of the N1-P2 complex responded differently to listening training.
      That is, significant changes in P1 and N1 amplitude were recorded over the right
      but not the left hemisphere. In contrast, increases in P2 were observed
      bilaterally. These results indicate that training-related changes in neural
      activity are reflected in far-field aggregate neural responses and that distinct
      patterns of neural change, perhaps reflecting hemispheric specialization, likely
      represent different aspects of auditory function.

PMID- 12069009
TI  - Listening effort and fatigue in school-age children with and without hearing
      loss.
AB  - Parents, audiologists, and educators have long speculated that children with
      hearing loss must expend more effort and, therefore, fatigue more easily than
      their peers with normal hearing when listening in adverse acoustic conditions.
      Until now, however, very few studies have been conducted to substantiate these
      speculations. Two experiments were conducted with school-age children with mild
      to-moderate hearing loss and with normal hearing. In the first experiment,
      salivary cortisol levels and a self-rating measure were used to measure fatigue.
      Neither cortisol measurements nor self-rated measures of fatigue revealed
      significant differences between children with hearing loss and their normal
      hearing peers. In the second experiment, however, a dual-task paradigm used to
      study listening effort indicated that children with hearing loss expend more
      effort in listening than children with normal hearing. Results are discussed in
      terms of clinical application and future research needs.

PMID- 12069011
TI  - Auditory temporal processing performance of young adults with reading disorders.
AB  - The present study investigated the temporal processing abilities of college
      students with diagnosed reading disorders. A behavioral test battery was used
      that involved discrimination of the pattern of presentation of tone triads in
      which individual components differed in either frequency or duration. An
      additional test involving measurement of frequency difference limens for long-
      and short-duration tones was also administered. The college students with reading
      disorders exhibited significantly higher error rates in discriminating duration
      patterns than the normal reading group. No group differences were found for the
      frequency pattern discrimination task. Both groups exhibited larger frequency
      difference limens with the shorter 20- and 50-ms tones than with the 200-ms
      tones. Significant correlations were found between reading ability measures and
      temporal processing abilities, specifically in word recognition and duration
      pattern processing, suggesting a relationship between lower level auditory
      temporal processing skills and decoding efficiency.

PMID- 12069010
TI  - Lexical and talker effects on word recognition among native and non-native
      listeners with normal and impaired hearing.
AB  - Evidence suggests that word recognition depends on numerous talker-, listener-,
      and stimulus-related characteristics. The current study examined the effects of
      talker variability and lexical difficulty on spoken-word recognition among four
      groups of listeners: native listeners with normal hearing or hearing impairment
      (moderate sensorineural hearing loss) and non-native listeners with normal
      hearing or hearing impairment. The ability of listeners to accommodate trial-to
      trial variations in talkers' voice was assessed by comparing recognition scores
      for a single-talker condition to those obtained in a multiple-talker condition.
      Lexical difficulty was assessed by comparing word-recognition performance between
      lexically "easy" and "hard" words as determined by frequency of occurrence in
      language and the structural characteristics of similarity neighborhoods
      formalized in the Neighborhood Activation Model. An up-down adaptive procedure
      was used to determine the sound pressure level for 50% performance. Non-native
      listeners in both normal-hearing and hearing-impaired groups required greater
      intensity for equal intelligibility than the native normal-hearing and hearing
      impaired listeners. Results, however, showed significant effects of talker
      variability and lexical difficulty for the four groups. Structural equation
      modeling demonstrated that an audibility factor accounts for 2-3 times more
      variance in performance than does a linguistic-familiarity factor. However, the
      linguistic-familiarity factor is also essential to the model fit. The results
      demonstrated effects of talker variability and lexical difficulty on word
      recognition for both native and nonnative listeners with normal or impaired
      hearing. The results indicate that linguistic and indexical factors should be
      considered in the development of speech-recognition tests.

PMID- 12069012
TI  - Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae
      bacteremia and is associated with the outcome of the disease.
AB  - YKL40 is secreted by activated macrophages and neutrophils. Elevated serum
      concentrations of YKL40 are found in patients with diseases characterized by
      inflammation or ongoing fibrosis. The aim of this study was to evaluate serum YKL
      40 levels in patients with Streptococcus pneumoniae bacteremia and to correlate
      these levels with clinical findings and outcomes. YKL40 was determined by ELISA
      and 89 patients were included in the study. Serum YKL-40 levels were
      significantly higher in patients with S. pneumoniae bacteremia (median 342
      microg/l; range 20-20,400 microg/l) than in age-matched healthy subjects (44
      microg/l; 20-184; p < 0.001). Serum YKL-40 levels were related to the severity of
      the infection, with significantly higher serum YKL-40 levels being observed in
      patients who needed hemodialysis (p < 0.001), pharmacological treatment of
      hypotension (p < 0.001) and mechanical ventilation (p = 0.003) compared to those
      in patients who did not need this supportive treatment. Nineteen patients died
      and these patients had significantly higher serum YKL-40 levels (980 microg/l; 88
      20,400 microg/l) than those of survivors (256 microg/l; 20-9,100 microg/l; p <
      0.001). Serum YKL40 level was an independent prognostic factor of survival in
      logistic multivariate regression analysis (p = 0.002). In conclusion, high serum
      levels of YKL40 indicated a poorer prognosis for patients with S. pneumoniae
      bacteremia.

PMID- 12069013
TI  - In vitro susceptibility to quinolones of Francisella tularensis subspecies
      tularensis.
AB  - Francisella tularensis is a potent pathogen and a possible bioterrorism agent,
      for which quinolones offer promising new therapeutic options. There are, however,
      no data on the susceptibility to quinolones of natural isolates of F. tularensis
      tularensis, the highly virulent North American subspecies. In the present study,
      8 isolates of F. tularensis tularensis, originating from 8 different states of
      the USA, and 16 US isolates of F. tularensis holarctica were tested. All 24
      isolates showed MIC values < or = 0.125 mg/l to 6 different quinolones. Against
      ciprofloxacin, the predominant quinolone used to date in therapy against
      subspecies holarctica, MIC values were consistently < or = 0.064 mg/l. Thus
      quinolones seem to be promising options for the treatment of tularemia, including
      cases caused by the highly virulent subspecies F. tularensis tularensis.

PMID- 12069014
TI  - Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV
      prevalence setting in Ethiopia: clinical, diagnostic and epidemiological
      characteristics.
AB  - In a setting with a high prevalence of HIV we studied (i) the prevalence of
      pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological
      characteristics of PTB; and (iii) the usefulness of standard procedures for
      diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of
      PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non
      TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases,
      respectively. Predictors for culture-verified PTB were age < 25 y, male gender
      and the presence of HIV and fever, whereas profound weight loss indicated HIV
      infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for
      acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific
      (64.1%). In HIV-positive patients both sensitivity and specificity were
      significantly lower (p < 0.05). HIV-related pulmonary infections are often
      misinterpreted as smear-negative PTB. HIV screening is therefore warranted not
      only in cases of verified TB but also as part of the diagnostic work-up in
      patients with respiratory symptoms suggestive of PTB. Also, increased awareness
      of, and improved diagnostic tools for, HIV-related pulmonary infections other
      than PTB are required, together with algorithms for patients with suspected PTB.

PMID- 12069015
TI  - Genitourinary tuberculosis: a review of 174 cases.
AB  - In 174 cases of genitourinary tuberculosis diagnosed and treated in our clinic we
      evaluated, retrospectively, age and sex distributions, symptoms, physical and
      laboratory findings, primary focus, surgical and medical treatments. Flank pain
      and non-specific urinary complaints, e.g. dysuria, were the major symptoms.
      Although some authors prefer short-term medical therapy for the treatment of
      genitourinary tuberculosis, the relapse rate in our series after 12 months of
      therapy was 19% and we therefore suggest that therapy should be continued for at
      least 12 months. The poor nutritional status and social conditions characteristic
      of subjects from our region may, however, have influenced this high relapse rate.

PMID- 12069016
TI  - Three major Lyme Borrelia genospecies (Borrelia burgdorferi sensu stricto, B.
      afzelii and B. garinii) identified by PCR in cerebrospinal fluid from patients
      with neuroborreliosis in Sweden.
AB  - The Lyme Borrelia genospecies Borrelia afzelii and B. garinii have previously
      been isolated using a culture method in Swedish patients with Lyme borreliosis
      (LB). There are reports suggesting that the genospecies distribution in human
      tissue specimens as determined by molecular methods is different from that
      obtained by culture. In the present study, we developed a nested PCR for
      detection of Lyme Borrelia-specific DNA in cerebrospinal fluid from Swedish
      patients with LB. The genospecies were subsequently identified by sequence
      analysis in a total of 7 PCR-positive patients. Two sequences were identified as
      B. burgdorferi sensu stricto (s. s.), 1 as B. afzelii and 4 as B. garinii. These
      are the first reported cases in which B. burgdorferi s. s. has been shown to be
      the causative agent of human LB in Sweden. The results of our study confirm that
      the use of direct molecular analytical methods for Borrelia genospecies
      identification in clinical specimens can provide epidemiological information
      additional to that obtained by culture.

PMID- 12069017
TI  - Leukocyte depleted, unscreened blood products give a low risk for CMV infection
      and disease in CMV seronegative allogeneic stem cell transplant recipients with
      seronegative stem cell donors.
AB  - Leukocyte depletion (LD) by blood product filtration has been shown to be
      similarly effective to the use of screened, CMV seronegative blood products to
      prevent CMV disease in CMV seronegative allogeneic stem cell transplant (SCT)
      patients with CMV seronegative donors. The aim of this retrospective study was to
      determine the risk for development of CMV infection requiring preemptive therapy
      and for CMV disease if unscreened products treated by prestorage LD is used.
      Forty-nine consecutive patients transplanted after June 1995 were included. As a
      control group, 33 patients transplanted from January 1992 to June 1995 in whom a
      combination of CMV seronegative and LD blood products were given. All patients
      were monitored weekly by a leukocyte-based PCR for CMV DNA detection. Preemptive
      therapy was initiated after two consecutively positive tests. No patient
      developed CMV disease in either group. CMV DNA was detected in 6/49 (p = NS) in
      the study group and in 3/33 patients in the historical control group. Two
      patients in the study group were given preemptive therapy compared to one patient
      in the control group. This study suggests that the risk for CMV disease and the
      need for preemptive therapy against CMV is low in CMV seronegative allogeneic SCT
      patients receiving grafts from CMV seronegative stem cell donors receiving LD
      blood products. Thus, this strategy can be safely used together with PCR
      monitoring and preemptive therapy.

PMID- 12069018
TI  - Detection of CMV in plasma and aqueous humor specimens from AIDS patients with
      CMV retinitis using the amplicor CMV test.
AB  - A DNA hybridization test (the Amplicor CMV test) for CMV DNA was used to detect
      CMV DNA in paired plasma and aqueous humor specimens from 37 AIDS patients with
      ophthalmoscopically diagnosed CMV retinitis. CMV was detected in 25/37 (67.6%)
      plasma specimens and in 32/37 (86.5%) aqueous humor specimens. Thus, the Amplicor
      CMV test using aqueous humor specimens seems to be a useful diagnostic test for
      CMV retinitis and one that is more sensitive than determination of CMV DNA in
      plasma specimens.

PMID- 12069019
TI  - Proposed criteria for classification of new genotypes of mumps virus.
AB  - The nucleotide sequences of a 300 bp segment carrying the small hydrophobic (SH)
      protein gene of a large number of virus strains, belonging to 10 different mumps
      virus genotypes denoted A-J, were compared. When virus strains belonging to the
      same genotype were compared intra-genotypically, a variation in the range 2-4%
      was recorded. The level of inter-genotypical variation was higher (8-18%). A
      consistent finding was the more pronounced variation found when the A genotype
      was compared to the B-J genotypes than when the B-J genotypes were compared among
      themselves. A similar relatively more pronounced genetic variation between the A
      and B-D genotypes has also been found previously with the hemagglutinin
      neuraminidase and fusion protein genes. It is concluded that the establishment of
      a new genotype should be founded on a nucleotide variation of the SH gene of > or
      = 6% in relation to previously described genotypes.

PMID- 12069020
TI  - Benefits of management strategy adjustments during an outbreak of enterovirus
      meningitis in adults.
AB  - Enteroviruses (EVs) are the most common identifiable cause of the aseptic
      meningitis syndrome. Widespread seasonal outbreaks of EV meningitis result in a
      high financial cost to the community, in part because of the difficulty of
      discriminating between viral and bacterial meningitis. During a nationwide
      outbreak of EV meningitis due to echovirus 30 in France we tested the hypothesis
      that a management strategy including early testing of cerebrospinal fluid (CSF)
      by means of EV PCR in all adult patients with acute aseptic meningitis on
      admission might reduce the duration of hospitalization and thus the expenditure
      on health resources. We compared the characteristics of adult patients with acute
      aseptic meningitis seen in our institution before (n = 21) and after (n = 27)
      implementation of this strategy. The strategy was cost-effective in that it
      significantly reduced (i) the mean duration of hospital stay (from 103 to 80 h; p
      = 0.04); and (ii) the mean duration of antibacterial treatment (from 115 to 69 h;
      p = 0.02). Systematic testing of CSF in adult patients with aseptic meningitis by
      means of EV PCR may be cost-effective during an outbreak of EV meningitis.

PMID- 12069022
TI  - Antibiotic prescription rates vary markedly between 13 European countries.
AB  - There is a lack of data on antibiotic utilization in most European countries. In
      this study, information about the number of antibiotic prescriptions was obtained
      for Austria, Belgium, Finland, France, Germany, Greece, Italy, The Netherlands,
      Portugal, Spain and the UK from the Institute for Medical Statistics Health
      Global Services in the UK. For Denmark and Sweden the information was obtained
      from the Danish Medicines Agency (Laegemiddelstyrelsen) and the National
      Corporation of Swedish Pharmacies (Apoteket AB), respectively. Between 1994 and
      1997 the number of prescriptions per 1,000 inhabitants increased in France and
      Greece whilst Portugal, Spain and Sweden reported a decrease. In 1997, Greece
      (1,350), Spain (1,320) and Belgium (1,070) had the highest numbers of antibiotic
      prescriptions per 1,000 inhabitants in the Anatomical Therapeutic Chemical
      classification system for drugs group J01 while The Netherlands (390), Sweden
      (460) and Austria (480) had the lowest. The most common antibiotic drug was
      extended-spectrum penicillin in 6/13 countries, macrolides in Austria, Finland,
      Germany and Italy, phenoxymethylpenicillin in Denmark and Sweden and
      cephalosporins in Greece. The variation in the number of antibiotic prescriptions
      per 1,000 inhabitants between the 13 European countries was substantial in terms
      of both total use and use of different antibiotics.

PMID- 12069021
TI  - Serological survey of Toxoplasma gondii infection in pigs slaughtered in Sweden.
AB  - The prevalence of Toxoplasma gondii infection in Swedish pigs was investigated by
      analysis of 807 meat juice samples collected in 1999 from 10 abattoirs in
      different parts of the country. When analysed using ELISA, 42 (5.2%) of the
      samples were found to be positive. The seroprevalence was 3.3% in fattening pigs
      (n = 695) and 17.3% (n = 110) in adult swine. Alternative interpretations of the
      results, considering estimates of the true prevalence based on the sensitivity
      and specificity of the test method, are discussed. It is concluded that the risk
      of contracting T. gondii infection as a result of eating undercooked pork from
      Swedish pigs, especially adult animals, is not negligible.

PMID- 12069023
TI  - Long-term antibiotic resistance surveillance of gram-negative pathogens suggests
      that temporal trends can be used as a resistance warning system.
AB  - Antibiotic resistance among Gram-negative bacteria and antibiotic consumption
      were investigated at the Karolinska Hospital, Stockholm, Sweden over a 12-y
      period. The investigation showed an increase in ciprofloxacin resistance of
      Escherichia coli from 0% in 1991 to 7% in 1997 and to 11% in 1999. Resistance
      among Pseudomonas aeruginosa isolates to ciprofloxacin increased from 2.5% in
      1991 to 9.0% in 1997 and to 13% in 1999. Resistance levels for norfloxacin showed
      the same high statistical significance in terms of the temporal trend. A more
      detailed analysis showed higher resistance against norfloxacin in specific wards.
      Relationships between antibiotic use and antibiotic susceptibility showed
      different patterns. The increased ciprofloxacin resistance of E. coli and P.
      aeruginosa during the study period was paralleled by an increased consumption of
      quinolones. During the 12-y study period the total use of cephalosporins
      increased 2.5-fold, while the levels of E. coli resistance to cefuroxime and
      cefotaxime remained stable. A third pattern was seen with trimethoprim
      sulfamethoxazole, namely increasing resistance of E. coli as the use of
      trimethoprim-sulfamethoxazole declined. The analysis of resistance levels and
      antibiotic consumption in the present study suggests different mechanisms for the
      increased resistance. The significant trend of increased resistance to
      antibiotics over time constitutes an important warning system.

PMID- 12069024
TI  - Sequelae after bacterial meningitis in childhood.
AB  - The neurological outcome of bacterial meningitis in children was evaluated
      retrospectively. Data were obtained from a large study on children aged between 1
      month and 15 y who initially visited the emergency department of Sophia
      Children's Hospital, Rotterdam, The Netherlands with meningeal signs. This study
      presents data from 103 patients in whom bacterial meningitis was diagnosed.
      Neisseria meningitidis was the dominant pathogen of meningitis. We found a 2%
      case-fatality rate in children with bacterial meningitis and a 13% rate of
      sequelae among survivors: 7% hearing impairment and 7% neurological sequelae.
      Children with bacterial meningitis caused by Streptococcus pneumoniae and those
      with acute focal neurological symptoms tended to have the worst prognosis.

PMID- 12069025
TI  - Listerial endocarditis in a penicillin-allergic woman successfully treated with a
      combination of 4 drugs.
AB  - A 69-y-old woman with bioprosthetic endocarditis due to Listeria monocytogenes
      developed an allergic reaction after beginning ampicillin treatment. She was
      cured with the combination of trimethoprim-sulfamethoxazole, rifampicin and
      teicoplanin. No immune deficiency was found in the patient.

PMID- 12069026
TI  - Neonatal nosocomial pneumococcal infections acquired by patient-to-patient
      transmission.
AB  - A case of neonatal nosocomial pneumococcal sepsis acquired by patient-to-patient
      transmission and confirmed by phenotypic and genotypic typing is documented. To
      the best of our knowledge this is the first documented case of neonatal
      nosocomial person-to-person transmission.

PMID- 12069027
TI  - Hepatic actinomycosis: an overview of salient features and outcome of therapy.
AB  - A 34-y-old African-American male developed Actinomyces liver abscess 8 months
      after appendectomy. Review of the English language literature revealed 56
      additional cases of hepatic actinomycosis. Affected patients were typically
      immunocompetent, had a wide age range (4-86 y) and were predominantly male
      (70.2%). Infection was frequently (80.7%) cryptogenic, presenting with fever
      (83.3%), abdominal pain (74.5%) and weight loss (50.9%) over a 3.7 +/- 5.1 month
      period. The most common radiographic finding was a single hypodense mass/abscess
      (68.4%). Extension to surrounding tissues was evident in 19 cases (33.3%).
      Diagnosis was usually accomplished microscopically and culture was often (33.3%)
      negative. Infection was often (35.2%) mixed, usually with anaerobic bacteria. A
      surgical or percutaneous approach was diagnostic in 29/35 (82.9%) and 24/33
      (72.7%) cases, respectively. The overall mortality rate was 8.8%; it was 10.7%
      with medical therapy alone and 4.0% using a combined medical/intervention
      approach (p = 0.6). In conclusion, hepatic actinomycosis is a rare subacute
      infection that may mimic neoplasm. It is usually cryptogenic, is more common
      among immunocompetent individuals and male subjects and is highly responsive to
      medical therapy.

PMID- 12069028
TI  - Stenotrophomonas maltophilia meningitis, bacteremia and respiratory infection.
AB  - Stenotrophomonas maltophilia is an increasingly recognized cause of nosocomial
      infection of special interest because of its resistance to multiple antimicrobial
      agents. We report a case of generalized infection by S. maltophilia, including
      meningitis, bacteremia and respiratory tract infection, in a patient who had
      undergone multiple neurosurgical procedures and who was treated with trimethoprim
      sulphamethoxazole.

PMID- 12069029
TI  - Deep venous thrombosis associated with pulmonary tuberculosis and transient
      protein S deficiency.
AB  - Vascular complications associated with Mycobacterium tuberculosis infection have
      rarely been reported in children. We describe a case of deep venous thrombosis of
      the left leg in association with pulmonary tuberculosis. The patient had
      transient protein S deficiency and anticardiolipin IgG and IgM antibodies were
      also present. The pathogenesis of the hypercoagulable state in tuberculosis is
      discussed.

PMID- 12069030
TI  - An extremely uncommon infection: Candida glabrata arthritis after total knee
      arthroplasty.
AB  - Prosthetic arthritis caused by Candida species is extremely rare. Of 30 such
      cases reported in the English literature, only 3 were due to Candida glabrata. We
      present herein a fourth case; to the best of our knowledge this is the first
      example of knee arthroplasty infection caused by C. glabrata.

PMID- 12069031
TI  - Diabetes insipidus as a complication of cryptococcal meningitis in an HIV
      infected patient.
AB  - We describe an HIV-infected patient with central diabetes insipidus as a
      complication of cryptococcal meningitis. Nephrogenic diabetes insipidus as a
      result of amphotericin B treatment is a rare but known complication. Central
      diabetes insipidus in cryptococcal meningitis has not been reported before. The
      patient responded well to desmopressin treatment.

PMID- 12069032
TI  - Another 2 cases of group B streptococcal sacroiliitis.

PMID- 12069033
TI  - Trends in Streptococcus pyogenes resistance to erythromycin in Slovakia: is there
      a correlation with consumption?

PMID- 12069034
TI  - The circadian clock as a molecular calendar.
AB  - There are two dominant environmental oscillators shaping the living conditions of
      our world: the day-night cycle and the succession of the seasons. Organisms have
      adapted to these by evolving internal clocks to anticipate these variations. An
      orchestra of finely tuned peripheral clocks slaved to the master pacemaker of the
      suprachiasmatic nuclei (SCN) synchronizes the body to the daily 24h cycle.
      However, this circadian clockwork closely interacts with the seasonal time
      teller. Recent experiments indeed show that photoperiod--the dominant Zeitgeber
      of the circannual clock--might be deciphered by the organism using the tools of
      the circadian clock itself. From the SCN, the photoperiodic signal is transferred
      to the pineal where it is decoded as a varying secretion of melatonin. Different
      models have been proposed to explain the mechanism by which the circadian clock
      measures day-length. Recent work using mutant mice suggests a set of two
      molecular oscillators tracking dusk and dawn, respectively, thereby translating
      day-length to the body. However, not every aspect of photoperiodism is covered by
      this theory and majoradjustments will need tobe made toestablish a widely
      acceptable uniform model of circadian/circannual timekeeping.

PMID- 12069035
TI  - Circadian period lengths of lipid synthesis mutants (cel, chol-1) of Neurospora
      show defective temperature, but intact pH-compensation.
AB  - The influence of extracellular pH on the circadian sporulation rhythm of
      Neurospora crassa has been investigated for the mutants chol-1 and cel. Both
      mutants have a defect in the lipid synthesis pathway and require either choline
      or palmitate, respectively, as supplements for normal growth. The chol-1 and cel
      mutants also show an impaired temperature-compensation when growing on minimal
      medium. We investigated the possible correlation between loss of temperature- and
      pH-compensation in cel and chol-1 similar to the correlation found earlier for
      the frq7 mutant. Our results show that the cel and the chol-1 mutants, although
      defective in temperature-compensation have an intact pH-compensation of their
      circadian rhythms. At present, the products of the frq-locus are the only
      components of the clock that affect the sporulation rhythm of Neurospora both
      through pH- and temperature-compensation.

PMID- 12069036
TI  - Circadian modulation of starvation-induced hypothermia in sheep and goats.
AB  - Prolonged food deprivation is known to cause a fall in the core body temperature
      of homeotherms. In various species of small birds and mammals (body mass up to 2
      3 kg), it has been shown that starvation-induced hypothermia is modulated by the
      circadian system, in the sense that hypothermia is observed primarily during the
      inactive phase of the daily activity cycle (i.e., during the night for diurnal
      animals and during the day for nocturnal animals), whereas relatively normal
      temperatures are recorded during the active phase. To investigate whether this
      modulation occurs also in larger animals, we investigated the effects of 4 d food
      deprivation on the body temperature rhythm of goats and sheep (body mass 30-40
      kg). In goats, the body temperature rhythm was found to have a mean level of 39.0
      degrees C with a mean daily range of excursion of 0.42 degrees C. The daily
      oscillation in body temperature persisted during the first day of fasting, but
      the rhythm was drastically damped, if not eliminated, over the next 3 d as body
      temperature descended from the baseline level of 39.0 to 38.2 degrees C. In
      sheep, the rhythm was found to have a mean level of 39.3 degrees C with a mean
      daily range of excursion of 0.34 degrees C. The daily oscillation in body
      temperature persisted through the 4 d of food deprivation, even though the mean
      level of body temperature gradually fell. Temperature fell more during the third
      and fourth nights than during the third and fourth days. Thus, circadian
      modulation of starvation-induced hypothermia was observed in sheep but not in
      goats.

PMID- 12069037
TI  - Mothering influences the distribution of activity in young domestic chicks.
AB  - The aim of this study was to determine whether the presence of a maternal hen
      influences the quality, quantity, and distribution of activity in young chicks.
      Brooded and nonbrooded chicks were observed during the entire light phase when
      they were 4 d of age. Our results revealed that although both brooded and
      nonbrooded chicks expressed the same behavioral items and in quite the same
      quantity, activity bouts were much longer in brooded chicks. However, only
      brooded chicks presented a high level of ultradian rhythmicity. Moreover, the
      brooded chicks made greater use of the space. The presence and the behavior of
      maternal hens appeared to provide structuring factors for the expression of the
      chicks behavior.

PMID- 12069038
TI  - The validity of the temporal parameters of the daily rhythm of melatonin levels
      as an indicator of morningness.
AB  - The present study tested the assumption that the temporal parameters of melatonin
      synthesis indicate the individual circadian phase position better than the
      minimum of rectal temperature. Thirty-four men and 17 women (16-32 yr, 14
      morning, 14 neither, 23 evening types) completed a constant routine (24-26 h
      bedrest, <30 lux, 18-20 degrees C, hourly isocaloric diet). Salivary melatonin
      level was determined hourly, rectal temperature and heart rate were continuously
      recorded throughout. The minima of rectal temperature and heart rate as well as
      the temporal parameters of melatonin synthesis occurred earlier in morning than
      in evening types and were significantly related to the subjective circadian phase
      as determined by the morningness-eveningness questionnaire. The level of
      significance and the resolving power was greater for the melatonin parameters and
      for the minimum of heart rate than for the minimum of rectal temperature. The
      temporal differences between the opposite diurnal types were larger and the
      correlation coefficients with morningness were higher in men than in women. The
      temporal parameters of melatonin synthesis are valid indicators of the individual
      circadian phase. As morningness is closely related to the ability to cope with
      shiftwork, the determination of the melatonin profile might be a valuable element
      of the criteria when assigning a person to shiftwork.

PMID- 12069039
TI  - A comparison of the suitabilities of rectal, gut, and insulated axilla
      temperatures for measurement of the circadian rhythm of core temperature in field
      studies.
AB  - Eight healthy males were studied for a total of 13 subject-days to assess if gut
      (from an ingested pill) and axilla (from a thermally insulated skin probe)
      temperatures would act as a substitute for rectal temperature in field studies of
      the circadian rhythm of core temperature. Subjects slept and went about their
      activities, indoors and outdoors, normally. Regular recordings (at 6 min
      intervals) were made of temperatures from the three sites. In addition, activity
      was measured (by a sensor on the nondominant wrist) so that the raw temperature
      data could be "purified," that is, corrected for the direct effects of sleep and
      activity. Inspection of the raw data indicated that there was a close parallelism
      between rectal and gut temperatures, but that the parallelism between rectal and
      insulated axilla temperatures was less reliable. This parallelism was supported
      by initial calculations of the correlations between rectal and gut temperatures
      (high and positive) and between rectal and insulated axilla (lower, though still
      positive) temperatures. Calculation of the limits of agreement between the
      parameters of the cosine curves fitted to the raw data confirmed that the rectal
      and gut temperatures were far closer with regard to acrophase and amplitude than
      were rectal and insulated axilla temperatures (-0.31 +/- 0.89 vs. +0.75 +/- 6.03
      h and +0.002 +/- 0.116 vs. +0.083 +/- 0.625 degrees C, respectively). After
      purification of the temperature data, the limits of agreement for the cosine
      parameters acrophase and amplitude still indicated that there was a closer
      agreement between rectal and gut temperatures than between rectal and insulated
      axilla temperatures (-0.30 +/- 1.12 vs. +0.58 +/- 6.69 h, and +0.007 +/- 0.116
      vs. +0.104 +/- 0.620 degrees C, respectively). Part of the explanation of this
      difference was the unreliable relationships between temperature changes in
      insulated axilla temperature and bursts of activity and going to bed. It is
      concluded that, whereas gut temperature is a viable alternativ to rectal
      temperature (from the viewpoints of both user acceptability and the reliability
      of data obtained), insulated axilla temperature, though acceptable to subjects,
      is unreliable from an experimental viewpoint.

PMID- 12069040
TI  - Circadian and seasonal variation of endogenous ubiquinone plasma level.
AB  - Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial
      electron transport chains, is a powerful antioxidant and membrane stabilizer that
      may prevent cellular damage during myocardial ischemia and reperfusion therapy.
      Coenzyme Q10 has been used primarily as an adjuvant therapy for some
      cardiomyopathies. However, one of the main problems in CoQ10 administration is
      the high variability of endogenous plasma and tissue levels, which seems to be
      dependent on several factors. This work explores temporal 24h and seasonal
      variation as well as gender and racial differences in endogenous plasma
      ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16
      healthy volunteers were done during the daytime hours of activity beginning at
      09:00h one day and ending at 09:00h the next day (13 different determinations) in
      two distinct months. April and October, of the year. A statistically significant
      circadian rhythm in plasma ubiquinone concentration that includes only the
      fundamental 24h component was demonstrated both in the April and October data.
      Furthermore, the time-point means of the ubiquinone concentration in the October
      study were invariably higher than those obtained in the April study. No
      statistically significant differences were found in CoQ10 concentration between
      male and female subjects, both in April and in October. In addition, racial
      differences were demonstrated; lower plasma ubiquinone levels were found in
      Caucasian compared to African subjects. However, the latter small group of
      subjects failed to demonstrate a circadian rhythm, neither in the April nor in
      the October analysis.

PMID- 12069041
TI  - Accidents in children do not happen at random: predictable time-of-day incidence
      of childhood trauma.
AB  - In a prospective study, 15,110 childhood traumas were recorded by the Pediatric
      Surgery Service (CHUV, Lausanne) between January 1, 1990 and December 31, 1997.
      The exact clock hour when the injury occurred and other germane data were
      obtained. Time series thus obtained were analyzed by several statistical (ANOVA,
      cosinor, chi2, Table Curve, etc.) methods. High statistically significant
      circadian patterns were detected with a trough at night--almost no traumas/hour
      (t/h), and a peak in the afternoon (approximately 16:00h)--9.3 +/- 0.4 (SD) t/h.
      Such 24h variation was validated for the whole sample for the entire 8 yr study
      span as well as the data of each year. Neither gender- nor age-related
      differences in the 24h pattern were detected between children under 5 yr of age,
      who have not yet attended school and children from 5 to 16 yr of age, who attend
      school. Small but statistically significant differences in the 24h patterns were
      observed when categorized by the type of activity associated with the trauma and
      the place of trauma occurrence. The great stability of the 24h pattern in
      childhood trauma over the 8 yr study span suggests an endogenous origin in
      addition to the role presumably played by environmental factors. Periods of 12
      and 8h were also detected in the time series. The afternoon peak time of
      childhood traumas differs from that of adults, which is located approximately
      04:00h in rotating shift workers and automobile drivers and 06:00-08:00h in adult
      day-workers. The validation of a circadian pattern in childhood traumas with an
      afternoon peak should be taken into account in the design of children's
      preventative injury programs.

PMID- 12069042
TI  - Circadian rhythm of atrioventricular conduction predicts long-term survival in
      patients with chronic atrial fibrillation.
AB  - The R-R interval of the electrocardiogram during atrial fibrillation (AF) appears
      absolutely irregular. However, the Poincare plot of the R-R interval reveals a
      sector shape of distribution that is unique to AF. Furthermore, the height of
      lower envelope (LE1.0) of the distribution and the degree of scatter above the
      envelope (scattering index) may reflect the refractoriness and concealment of
      atrioventricular (AV) conduction, respectively. We previously observed that both
      the LE1.0 and scattering index show clear circadian rhythms in patients with
      chronic AF and that the rhythms are blunted in those with congestive heart
      failure and chronic AF. In the present study, we examined if the blunted
      circadian rhythm of the AV conduction has prognostic value in patients with
      chronic AF. We studied a retrospective cohort of 120 patients who underwent 24h
      Holter monitoring at baseline. During an observation period of 33 +/- 16 mon,
      there were 25 deaths (21%) including 13 cardiac and 8 stroke deaths. All patients
      showed significant circadian rhythms in both LE1.0 and scattering index with
      acrophases occurring at night; however, patients dying subsequently from cardiac
      causes, but not those from fatal stroke were blunted in the circadian rhythms
      (the amplitudes were < 55% of those in surviving patients). Furthermore, the
      reduced circadian amplitude of scattering index was an increased risk for cardiac
      death even after adjustment of coexisting cardiovascular risks [adjusted relative
      risk (95% confidence interval) per 1-SD decrement, 4.24 (1.54-11.6)]. When
      patients were divided by the circadian amplitude of the scattering index of 36.5
      msec (mean minus 1-SD), the 5yr cardiac mortality below and above the cutoff was
      57 and 6%, respectively (log-rank test, p < 0.001). We conclude that the blunted
      circadian rhythm of AV conduction is an independent risk for cardiac death in
      patients with chronic AF.

PMID- 12069043
TI  - Low, but not high, doses of melatonin entrained a free-running blind person with
      a long circadian period.
AB  - In a previous report, we were unable to entrain one out of seven totally blind
      people with free-running endogenous melatonin rhythms to 10 mg of exogenous
      melatonin. This person had the longest circadian period (24.9 h) of the group. We
      now find that this person can be entrained to 0.5 mg of melatonin, but not to 20
      mg. These results are consistent with the idea that too much melatonin may spill
      over onto the wrong zone of the melatonin phase-response curve.

PMID- 12069044
TI  - Hybrid materials from amphiphilic block copolymers and membrane proteins.
AB  - Self-assembly of reactive amphiphilic block copolymers is used to prepare
      nanostructured hydrogels with exceptional permeability properties, vesicular
      structures and planar, freestanding membranes in aqueous solution. Although the
      underlying block copolymer membranes are two-three-fold thicker than conventional
      lipid bilayers, they can be regarded as mimetic of biological membranes and can
      be used as a matrix for membrane-spanning proteins. Surprisingly, the proteins
      remain functional, despite the extreme thickness of the membranes and even after
      polymerization of the reactive block copolymers. The unique combination of block
      copolymers with membrane proteins allows the preparation of mechanically stable,
      defect-free membranes and nanocapsules that have highly selective permeability
      and/or specific recognition sites. This is documented by some representative
      examples.

PMID- 12069045
TI  - Porous polymers and resins for biotechnological and biomedical applications.
AB  - This review describes conventional and modern techniques of porous organic
      polymer synthesis. A huge variety of polymer architectures and functions can be
      gained by foaming, phase separation, imprinting or templating approaches. Several
      applications of porous polymers are discussed, focusing on biotechnological and
      biomedical applications, such as chromatography, protein synthesis, drug carrier
      systems, tissue engineering and others.

PMID- 12069047
TI  - Layer-by-layer self-assembly of supramolecular and biomolecular films.
AB  - In this paper, we give a short account on recent studies of layer-by-layer self
      assembly of supramolecular and biomolecular films. Such films are built up from
      layers of macro-ions with opposing charge. A simple film can be obtained by
      alternating the adsorption of two components: a flexible, synthetic polycation
      chains and a supramolecular or biomolecular moiety. We focus on three examples,
      in which the second component consists either of a supramolecular metal-organic
      complex (MOC), a nucleic acid, or a biological membrane patch (purple membrane).
      While the flexible polvcation chains (as well as eventual annealing layers)
      ensure a uniform build-up of the chain, the second macromolecular component may
      be used to functionalize the films. The combination of layer-by-layer self
      assembly and biotechnologically relevant macromolecules may lead to new devices
      or biomaterial applications. To this end, precise studies of the deposition
      process and the film structure are needed. Here, we focus on interface sensitive
      scattering techniques for the structural analysis.

PMID- 12069046
TI  - Poly(ethylene glycol) block copolymers.
AB  - The ubiquitous use of poly(ethylene glycol) in the biomaterials field has also
      boosted the research activity in the chemical derivatization of this polymer. We
      focused our interest on the preparation of tailor-made poly(ethylene glycol)
      based structures and on the study of structure-activity relationships for its
      functionalization, as preliminary steps for the preparation of smart functional
      materials. More specifically, amphiphilic and cationic block copolymers were
      prepared for prospective use in the preparation of self-assembled carriers, and
      Michael-type addition of thiols onto acrylates was studied as a model for end
      group reaction leading to hydrogel formation.

PMID- 12069048
TI  - Phthalate levels in beverages in Japan and Korea.

PMID- 12069049
TI  - Development of multiplexed fluorescence microbead covalent assays (FMCAs) for
      pesticide biomonitoring.

PMID- 12069050
TI  - Comparative studies on the acute toxicities of auxiliary chemicals used in
      textile finishing industry by bioluminescence test and neutral red test.

PMID- 12069051
TI  - Trace analysis of nicotine in indoor air by a SPME method.

PMID- 12069052
TI  - Safety measures in the application of organophosphate insecticides on staked
      tomato crops using dragged hoses.

PMID- 12069053
TI  - Safety evaluation and persistence of imidacloprid on acid lime (Citrus
      aurantiifolia Swingle).

PMID- 12069054
TI  - Leaching behavior of imidacloprid formulations in soil.

PMID- 12069055
TI  - Adsorption and mobility of acetochlor and butachlor on soil.

PMID- 12069056
TI  - Arsenic concentrations in house wrens from Whitewood Creek, South Dakota, USA.

PMID- 12069057
TI  - Preliminary study on some contaminant hydrocarbons in settled particles in
      Caracas City, Venezuela.

PMID- 12069058
TI  - Organochlorine pesticide residue concentrations in shrimps, sediments, and
      surface water from Bay of Ohuira, Topolobampo, Sinaloa, Mexico.

PMID- 12069059
TI  - Accumulation of chromium and scanning electron microscopic studies in Scirpus
      lacustris L. Treated with metal and tannery effluent.

PMID- 12069060
TI  - Fluid motion effect on metal toxicity in Bufo arenarum embryos.

PMID- 12069061
TI  - Heavy metal content of spoil heaps from an abandoned iron- and copper-mine and
      metal accumulation in Armeria linkiana nieto feliner.

PMID- 12069062
TI  - Induction of phytochelatins in Lemna aequinoctialis in response to cadmium
      exposure.

PMID- 12069063
TI  - Effect of chromium on the axenic growth and phosphatase activity of
      ectomycorrhizal fungi, Laccaria laccata and Suillus bovinus.

PMID- 12069064
TI  - Mercury content in shrimp and fish species from the Gulf coast of Saudi Arabia.

PMID- 12069065
TI  - Ultimobranchial gland of freshwater catfish, Heteropneustes fossilis in response
      to deltamethrin treatment.

PMID- 12069066
TI  - Effect of N,N-dimethyl formamide used as organic solvent on two species of green
      algae chlorella.

PMID- 12069067
TI  - Acute and chronic toxicity of pyrene to the unicellular marine alga Phaeodactylum
      tricornutum.

PMID- 12069068
TI  - Toxic effects of dimethoate and carbaryl pesticides on carbohydrate metabolism of
      freshwater snail Lymnaea acuminata.

PMID- 12069069
TI  - Lipid peroxidation and antioxidant defense systems in liver of rats in chronic
      fluoride toxicity.

PMID- 12069070
TI  - Nonsuppurative myocarditis associated with so-called fowl glioma.
AB  - C/O specific pathogen-free White Leghorn chickens were intracerebrally inoculated
      at one day of age with a brain homogenate of Japanese bantams (Gallus gallus
      domesticus) affected with fowl glioma. Histologically, six of eight inoculated
      chickens developed nonsuppurative meningoencephalitis in cerebrum and two of them
      had the characteristic lesions of fowl glioma. Hyperplastic lymphoid foci
      concomitantly developed in many organs of these birds, especially in the heart.
      Apart from these lymphoid foci, lymphocytic myocarditis was observed in all
      inoculated birds. Matrix inclusions were also noted in myocardial cells.
      Immunohistochemically, avian leukosis virus antigens were detected in reticular
      cells in the lymphoid foci, mesangial cells of the kidney, smooth muscle cells of
      the blood vessels, and myocardial cells. Of these tissues, the myocardium of all
      inoculated birds consistently showed strong reactivity for this antigens. The
      matrix inclusions were also positive for the antigens. These results suggest that
      the causal virus of fowl glioma has a high propensity to replicate, especially in
      myocardium and nonsuppurative myocarditis occurs associated with so-called fowl
      glioma.

PMID- 12069071
TI  - Determination of nitrotyrosine by HPLC-ECD and its application.
AB  - 3-nitrotyrosine, a product of tyrosine nitration, is a useful indicator of
      oxidative damage. We modified the previously reported HPLC-electrochemical
      detection (ECD) method: specifically, a through-type porous carbon electrode was
      used as a reducing electrode instead of the mercury-gold amalgam electrode,
      because the response of the latter changes over time. A combination of reverse
      phase HPLC and electrochemical detector passed through -800 mV reduction
      potential and subsequently under +250 mV oxidation potential allows measurement
      of 3-nitrotyrosine. The detection limit of this assay was less than 10 fmol. In
      mice to which lipopolysaccharide (LPS) was administered intraperitoneally, plasma
      3-nitrotyrosine levels were elevated, corresponding to LPS dosage. These findings
      suggest that the improved HPLC-ECD method can be used as a specific and sensitive
      assay of biological 3-nitrotyrosine and can be applied clinically.

PMID- 12069072
TI  - The correlation of protective effects and antibody production in immunized
      chickens with recombinant R7 vaccine against Leucocytozoon caulleryi.
AB  - Protective effects of recombinant R7 (rR7) vaccine against Leucocytozoon
      caulleryi in chickens were studied. After injection of oil-adjuvanted rR7 vaccine
      into chickens, antibody titers against second-generation schizonts (2GS) antigen
      of L. caulleryi (anti-2GS antibody) rapidly rose in all the immunized chickens,
      reached to a peak value 2 weeks after injection, and the titers persisted through
      4 or 5 months after injection. Chickens having high levels of the anti-2GS
      antibody titers (> or = 102,400 ) at pre-challenge completely protected against
      sporozoites challenge of L. caulleryi. After the challenge inoculation,
      relatively high parasitemia of L. caulleryi was observed in all the inadequately
      immunized chickens having low levels of the antibody titers (< or = 3,200) at pre
      challenge, although some of them seemed to be clinically normal. Correlation of
      protective effects in the immunized chickens was observed between both prevention
      of appearance of clinical signs and parasitemia after parasites challenge and
      anti-2GS antibody titers of the chickens at pre-challenge. The present study
      shows that chicken leucocytozoonosis can be prevented by vaccination, and humoral
      immunity may play an important role in the control of chicken leucocytozoonosis.

PMID- 12069073
TI  - The detection of the meq gene in chicken infected with Marek's disease virus
      serotype 1.
AB  - In the genome of strains of very virulent Marek's disease virus serotype
      1(vvMDV1), such as Md5 and RB1B, the meq open reading frame (ORF) encoding a 339
      amino-acid bZIP protein, is present, while a slightly longer meq ORF, termed as L
      meq, in which a 180-bp sequence is inserted into the meq ORF is found in other
      strains of MDV1, such as CV1988/R6 and attenuated JM. When chickens were infected
      with vvMDV1 strains and the meq gene was amplified by nested polymerase chain
      reaction (PCR), the meq gene was detected throughout the experimental period for
      7 weeks post inoculation (pi). However, the L-meq gene was also detected at 3 to
      5 weeks and 3 to 4 weeks pi. in Md5-infected and RB1B-infected chickens,
      respectively. In the case of chickens infected with an attenuated MDV1, the JM
      strain, the L-meq gene was detected at 2 to 7 weeks pi., and the meq gene was
      also detected at 2 to 6 weeks pi. Both L-meq and meq genes were detected in
      chickens infected with an attenuated nononcogenic vaccine strain of MDV1
      (CVI988/R6), throughout the experimental period. Though quantitative PCR was not
      performed, a larger amount of the PCR products corresponding to the L-meq than
      the meq gene was amplified from chickens infected with JM or CVI988/R6. These
      results suggest that a dynamic population shift between the MDV subpopulations
      displaying meq and L-meq genes occurs in chickens during the course of MDV
      infection. Since the MDV subpopulation that displays the L-meq gene only displays
      it during the latent phase, the L-meq and its gene product, if any, might
      contribute to the maintenance of the MDV latency.

PMID- 12069074
TI  - Bacterial lipopolysaccharide induces mRNA expression of an IkappaB MAIL through
      toll-like receptor 4.
AB  - Molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) is a
      nuclear IkappaB protein recently identified as a molecule appearing in
      immunocompetent organs after administration of bacterial lipopolysaccharide
      (LPS). Participation of Toll-like receptor (TLR) 4, which is a major form of LPS
      receptors, in the LPS-induced MAIL expression was investigated. When a human
      myelomonocytic cell line U937 was treated with phorbol 12-myristate 13-acetate
      for 3 days, the LPS-induced MAIL expression was much potentiated in parallel with
      an increase in TLR4 expression. The MAIL induction was attenuated when the cells
      were treated with a neutralizing antibody against TLR4. The in vivo induction of
      MAIL in the spleen was smaller in mice having a missense mutation of the Tlr4
      gene than in normal control mice. These results collectively indicate that TLR4
      contributes, at least in part, MAIL induction after LPS stimulation.

PMID- 12069075
TI  - Resistance of cotton rats, Sigmodon hispidus, to primary infection by
      Nippostrongylus brasiliensis.
AB  - The resistance of cotton rats, Sigmodon hispidus to Nippostrongylus brasiliensis
      infection was examined and compared the response to that of the susceptible
      Indian soft-furred rat, Millardia meltada. After a primary infection with
      infective third-stage N. brasiliensis larvae (L3), the number of eggs in feces
      and adult worm recovery rates from the small intestine of cotton rats were
      significantly lower than in the controls. To determine whether cotton rat
      resistance was observed during the migratory phase or the intestinal phase,
      cotton rats and control animals were challenged subcutaneously with L3 or
      intraduodenally with adult worms, and larval recovery from lungs and adult worm
      burden were evaluated. The recovery rate of larvae from the lungs of cotton rats
      was about five-fold lower than from controls. Adult worm recovery from the small
      intestine of cotton rats was also lower than that from the controls, but the
      difference (two-fold lower) was smaller than that observed for lung recovery.
      Carbon treatment at a dose of 250-500 mg/kg effectively increased larval worm
      recovery from the lungs of cotton rats. However, this treatment had no effect on
      worm recovery from the intestine after intraduodenal implantation of adult N.
      brasiliensis. These results suggest that macrophage function have important role
      in the expression of strong resistance during the migratory phase of N.
      brasiliensis infection in cotton rats.

PMID- 12069076
TI  - Availability of NMR microscopic observation of mouse embryo disorder: examination
      in malformations induced by maternal administration of retinoic acid.
AB  - Nuclear magnetic resonance (NMR) microscopy is a magnetic resonance imaging
      method with enhanced spatial resolution due to the use of a high static magnetic
      field and high magnetic field gradients. It is considered to be a useful tool for
      non-invasive and continuous investigation of tissue and organs at the
      histological level. In this study, we applied NMR microscopy to assessment of
      morphology in mouse embryos using a developmental disorder model induced by
      retinoic acid administration. Pregnant mice were given 50 mg/kg all-trans
      retinoic acid at 8.5 dpc. Embryos were collected at several time points after
      treatment and examined by NMR microscopy after fixation. Two-dimensional and
      three-dimensional spin echo sequences were used. Tissue contrast on two
      dimensional images changed according to length of repetition time and echo time,
      and also to developmental stage of embryos. Two-dimensional and three-dimensional
      images nondestructively demonstrated defects in development of the skeleton and
      soft tissue, e.g. hypoplasia of vertebrae in the lumbar and tail regions and
      dysplasia of the spinal cord, in embryos exposed to retinoic acid. These
      morphological abnormalities were confirmed by conventional assessment after
      imaging. Although further improvements are required, NMR microscopy will provide
      a new approach for multi-parameter assessment of embryonic development under
      physiological and pathological conditions.

PMID- 12069077
TI  - TRAIL-decoy receptor 1 plays inhibitory role in apoptosis of granulosa cells from
      pig ovarian follicles.
AB  - Previously, we histochemically examined the localization of tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand (TRAIL) and its receptors in porcine
      ovarian follicles, and demonstrated a marked reduction in the expression of TRAIL
      decoy receptor-1 (DcRI) in granulosa cells of atretic follicles. In the present
      study, to confirm the inhibitory activity of DcR1 in granulosa cells, granulosa
      cells prepared from healthy follicles were treated with phosphatidylinositol
      specific phospholipase C (PI-PLC) to cleave glycophospholipid anchor of DcR1 and
      to remove DcR1 from the cell surface, and then incubated with TRAIL. PI-PLC
      treatment increased the number of apoptotic cells induced by TRAIL. The present
      finding indicated the possibility that TRAIL and its receptors were involved in
      induction of apoptosis in granulosa cells during atresia, and that DcR1 plays an
      inhibitory role in granulosa cell apoptosis.

PMID- 12069078
TI  - CD56 is expressed exclusively on CD3+ T lymphocytes in canine peripheral blood.
AB  - CD56+ cells in canine blood leukocytes were characterized by flow-cytometric
      analysis of peripheral blood of 30 healthy adult beagle-dogs (15 males and 15 non
      pregnant females). In 19 of the 30 dogs, anti human CD56 antibody, Leu-19,
      reacted with 8.8-21.7% of peripheral blood lymphocytes. All CD56+ cells
      simultaneously expressed CD3 molecules on their surface. Further phenotypic
      analysis revealed that 50.6+/-13.1% of the CD56+ cells showed CD4-CD8+ phenotype
      and 43.7+/-10.1% showed CD4+CD8- phenotype. Expression intensity of CD56 on the
      CD4-CD8+CD56+ cells was significantly higher than that on CD4+CD8-CD56+ cells
      (P<0.001). These findings indicate that CD56, which is a neural cell adhesion
      molecule, is uniquely expressed on subsets of T lymphocytes in canine peripheral
      blood.

PMID- 12069079
TI  - Demonstration of continuously seropositive population against Borna disease virus
      in Misaki feral horses, a Japanese strain: a four-year follow-up study from 1998
      to 2001.
AB  - Borna disease virus (BDV)-specific antibodies were monitored in Misaki feral
      horses annually for 4 years using an electrochemiluminescence immunoassay
      (ECLIA). Among 130 horses examined, 35 (26.9%) with an ECLIA count above 1000
      once or more were judged as BDV seropositive. Throughout the study period, p24
      antibodies were more frequent than p40 antibodies in almost all positive animals.
      Among the 35 seropositive horses, the ECLIA count was consistently high in 12
      cases. Eleven horses seroconverted from negative to positive and 7 underwent
      reversal. The count in the remaining 95 horses (73.1%) remained low for 4 years
      and these animals were judged as seronegative.

PMID- 12069080
TI  - Detection of porcine circovirus 2 (PCV-2) DNA by nested PCR from formalin-fixed
      tissues of post-weaning multisystemic wasting syndrome (PMWS) pigs in Thailand.
AB  - A retrospective study for the detection of porcine circovirus 2 (PCV-2) DNA was
      conducted by nested PCR method in 16 cases of swine post-weaning multisystemic
      wasting syndrome (PMWS) in Thailand. Histopathology showed characteristic lesions
      of PMWS and intracytoplasmic viral inclusion bodies in macrophages infiltrating
      in lymphoid tissues. PCV-2 DNA was detected from formalin-fixed and/or formalin
      fixed paraffin-embedded tissues from all pigs with PMWS. The amplified products
      were digested with Hae III.

PMID- 12069081
TI  - Nucleotide sequence and expression of the feline vascular endothelial growth
      factor.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic factor which targets
      vascular endothelial cells. In this study, cDNA encoding a feline VEGF (fVEGF)
      isoform was cloned from a feline lymphoid tumor cell line and sequenced. The
      fVEGF cDNA contained an open reading frame of 567 nucleotides coding for a
      polypeptide of 163 amino acids with a putative signal peptide of 26 amino acids.
      The predicted fVEGF amino acid sequence shared 98.4, 94.2 and 94.2% homology with
      the sequences of canine, bovine and human VEGF, respectively. Though predicted
      fVEGF polypeptide was two amino acid residues shorter than human VEGF165, a
      potential glycosylation site and regions critical for receptor binding were
      conserved in all the species examined. Transient expression of fVEGF in mammalian
      cells resulted in secretion of VEGF which could be detected by antibodies against
      human VEGF165. Furthermore, wide expression of fVEGF mRNA was observed in various
      feline tissues using RT-PCR methods.

PMID- 12069083
TI  - Characterization of miniature tissue-equivalent proportional counters for neutron
      radiotherapy applications.
AB  - A miniature tissue-equivalent proportional counter (TEPC) system has been
      developed to facilitate microdosimetric measurements in high-flux mixed fields.
      Counters with collecting volumes of 12.3 and 2.65 mm3 have been constructed using
      various tissue-equivalent wall materials, including those loaded with 10B for
      evaluation of the effects of the boron neutron capture reaction. These counters
      provide a measure of both the absorbed dose and associated radiation quality,
      allowing an assessment of the utility and relative effectiveness of various
      neutron radiotherapy techniques such as boron neutron capture therapy (BNCT),
      boron neutron capture enhanced fast neutron therapy (BNCEFNT) and intensity
      modulated neutron radiotherapy (IMNRT). An evaluation of the physical parameters
      affecting the measured microdosimetric spectrum, the gas multiplication
      characteristics and the measurement of absorbed dose is presented. In addition,
      important aspects of the calibration and low energy extrapolation techniques for
      the microdosimetric spectrum are provided.

PMID- 12069082
TI  - Is there a correlation between the structure of hair and breast cancer or BRCA1/2
      mutations?
AB  - It has been suggested that the small angle x-ray scattering (SAXS) pattern of
      human hair can be used to diagnose breast cancer and possibly to identify BRCA1/2
      mutation carriers, who are at significantly elevated risk for developing breast
      cancer. In particular, the presence of a diffuse ring in the SAXS pattern was
      said to be diagnostic of either breast cancer or an increased risk thereof. To
      test this hypothesis, we measured SAXS from the pubic hair of 56 subjects with
      known BRCA1/2 and breast cancer status. We found that there is no clear
      association between the pattern of SAXS seen in human pubic hair and the risk of
      breast cancer or the presence of BRCA1/2 mutations. The possible use of SAXS to
      diagnose cancer remains conjectural, but this and previous studies do not suggest
      that SAXS can be used as a reliable method of identifying either BRCA1/2 mutation
      carriers or women who have had breast cancer.

PMID- 12069084
TI  - A deterministic iterative least-squares algorithm for beam weight optimization in
      conformal radiotherapy.
AB  - Currently, inverse treatment planning in conformal radiotherapy is, in part, a
      trial-and-error process due to the interplay of many competing criteria for
      obtaining a clinically acceptable dose distribution. A new method is developed
      for beam weight optimization that incorporates clinically relevant nonlinear and
      linear constraints. The process is driven by a nonlinear, quasi-quadratic
      objective function and the solution space is defined by a set of linear
      constraints. At each step of iteration, the optimization problem is linearized by
      a self-consistent approximation that is local to the existing dose distribution.
      The dose distribution is then improved by solving a series of constrained least
      squares problems using an established method until all prescribed constraints are
      satisfied. This differs from the current approaches in that it does not rely on
      the search for the global minimum of a specific objective function. Essentially,
      our proposed objective function can be construed as a functional that comprises a
      class of dose-based quadratic objective functions. Empirical adjustment for
      appropriate model parameters in the construction of objective function is
      minimized, since these parameters are in effect adaptively adjusted during
      optimization. The method is robust in solving difficult clinical cases using
      either aperture or pencil beam based planning techniques for intensity-modulated
      radiation therapy.

PMID- 12069085
TI  - Using voxel-dependent importance factors for interactive DVH-based dose
      optimization.
AB  - Intensity modulated radiation therapy (IMRT) inverse planning is usually
      performed by pre-selecting parameters such as beam modality, beam configuration
      and importance factors and then optimizing the fluence profiles or beamlet
      weights. In reality, the IMRT dose optimization problem may be ill-conditioned
      and there may not be a physical solution to account for the chosen parameters and
      constraints. Planner intervention is often required to conduct a multiple trial
      and-error process where several parameters are sequentially varied until an
      acceptable compromise is achieved. The resulting solution reflects a balance
      between the conflicting requirements of the target and the sensitive structures.
      A major problem of the conventional inverse planning formalism is that there
      exists no effective mechanism for a planner to fine-tune the dose distribution on
      a local level or to differentially modify the dose-volume histograms (DVHs) of
      the involved structures. In this paper we introduce a new inverse planning scheme
      with voxel-dependent importance factors and demonstrate that it provides us with
      an effective link between the system parameters and the dosimetric behaviour at a
      local level. The planning proceeds in two steps. After a conventional trial-and
      error inverse planning procedure is completed, we identify the dose interval at
      which the fractional volume on the DVH curve needs to be changed. The voxels that
      receive dose in the selected range are then located and their voxel-dependent
      importance factors are adjusted accordingly. The fine-tuning of the DVHs is
      iterative in nature and, using widely available computer graphic software tools,
      the process can be made graphically interactive. The new IMRT planning scheme is
      applied to two test cases and the results indicate that our control over the
      differential shapes of the DVHs of the involved structures is,greatly enhanced.
      Thus the technique may have significant practical implications in facilitating
      the IMRT treatment planning process.

PMID- 12069087
TI  - Evaluation of the EGSnrc Monte Carlo code for interface dosimetry near high-Z
      media exposed to kilovolt and 60Co photons.
AB  - High atomic number (Z) heterogeneities in tissue exposed to photons with energies
      of up to about 1 MeV can cause significant dose perturbations in their immediate
      vicinity. The recently released Monte Carlo (MC) code EGSnrc (Kawrakow 2000a Med.
      Phys. 27 485-98) was used to investigate the dose perturbation of high-Z
      heterogeneities in tissue in kilovolt (kV) and 60Co photon beams. Simulations
      were performed of measurements with a dedicated thin-window parallel-plate ion
      chamber near a high-Z interface in a 60Co photon beam (Nilsson et al 1992 Med.
      Phys. 19 1413-21). Good agreement was obtained between simulations and
      measurements for a detailed set of experiments in which the thickness of the ion
      chamber window, the thickness of the air gap between ion chamber and
      heterogeneity, the depth of the ion chamber in polystyrene and the material of
      the interface was varied. The EGSnrc code offers several improvements in the
      electron and photon production and transport algorithms over the older
      EGS4/PRESTA code (Nelson et al 1985 Stanford Linear Accelerator Center Report
      SLAC-265. Bielajew and Rogers 1987 Nucl. Instrum. Methods Phys. Res. B 18 165
      81). The influence of the new EGSnrc features was investigated for simulations of
      a planar slab of a high-Z medium embedded in water and exposed to kV or 60Co
      photons. It was found that using the new electron transport algorithm in EGSnrc,
      including relativistic spin effects in elastic scattering, significantly affects
      the calculation of dose distribution near high-Z interfaces. The simulations were
      found to be independent of the maximum fractional electron energy loss per step
      (ESTEPE), which was often a cause for concern in older EGS4 simulations.
      Concerning the new features of the photon transport algorithm sampling of the
      photoelectron angular distribution was found to have a significant effect,
      whereas the effect of binding energies in Compton scatter was found to be
      negligible. A slight dose artefact very close to high-Z interfaces exposed to
      kilovolt x-rays was discovered when atomic relaxation processes following
      excitation were omitted.

PMID- 12069086
TI  - A Monte Carlo dose calculation tool for radiotherapy treatment planning.
AB  - A Monte Carlo user code, MCDOSE, has been developed for radiotherapy treatment
      planning (RTP) dose calculations. MCDOSE is designed as a dose calculation module
      suitable for adaptation to host RTP systems. MCDOSE can be used for both
      conventional photon/electron beam calculation and intensity modulated
      radiotherapy (IMRT) treatment planning. MCDOSE uses a multiple-source model to
      reconstruct the treatment beam phase space. Based on Monte Carlo simulated or
      measured beam data acquired during commissioning, source-model parameters are
      adjusted through an automated procedure. Beam modifiers such as jaws, physical
      and dynamic wedges, compensators, blocks, electron cut-outs and bolus are
      simulated by MCDOSE together with a 3D rectilinear patient geometry model built
      from CT data. Dose distributions calculated using MCDOSE agreed well with those
      calculated by the EGS4/DOSXYZ code using different beam set-ups and beam
      modifiers. Heterogeneity correction factors for layered-lung or layered-bone
      phantoms as calculated by both codes were consistent with measured data to within
      1%. The effect of energy cut-offs for particle transport was investigated.
      Variance reduction techniques were implemented in MCDOSE to achieve a speedup
      factor of 10-30 compared to DOSXYZ.

PMID- 12069088
TI  - Diagnostic x-ray dosimetry using Monte Carlo simulation.
AB  - An Electron Gamma Shower version 4 (EGS4) based user code was developed to
      simulate the absorbed dose in humans during routine diagnostic radiological
      procedures. Measurements of absorbed dose using thermoluminescent dosimeters
      (TLDs) were compared directly with EGS4 simulations of absorbed dose in
      homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based
      models characterizing the geometry of the phantoms were used as input to the EGS4
      code. The voxel geometry of the anthropomorphic Rando phantom was derived from a
      CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus
      used to irradiate the phantoms were measured, and provided as input to the EGS4
      code. The TLDs were placed at evenly spaced points symmetrically about the
      central beam axis, which was perpendicular to the cathode-anode x-ray axis at a
      number of depths. The TLD measurements in the homogeneous and heterogenous
      phantoms were on average within 7% of the values calculated by EGS4. Estimates of
      effective dose with errors less than 10% required fewer numbers of photon
      histories (1 x 10(7)) than required for the calculation of dose profiles (1 x
      10(9)). The EGS4 code was able to satisfactorily predict and thereby provide an
      instrument for reducing patient and staff effective dose imparted during
      radiological investigations.

PMID- 12069089
TI  - The effect of wall thickness on the response of a spherical ionization chamber.
AB  - Air-filled ionization chambers are used widely for radiation dosimetry. For some
      applications it is important to know the effect on the chamber response of photon
      attenuation and scattering in the chamber walls. Traditionally, the wall effect
      is determined by measuring the chamber response as a function of wall thickness
      and extrapolating linearly to zero thickness. We have constructed a spherical
      graphite chamber with variable wall thickness. The change in the chamber response
      with wall thickness has been measured in a 137Cs gamma-ray beam. Our data show
      that the change in response is not linear with wall thickness, in agreement with
      the theoretical prediction of Bielajew (1990 Med. Phys. 17 583-7). A linear
      versus non-linear extrapolation of the measured data to zero wall thickness leads
      to a difference of almost 1% in the estimate of the wall correction factor, Kw.
      The value of Kw obtained using the non-linear extrapolation is in good agreement
      with the result obtained using Monte Carlo techniques.

PMID- 12069090
TI  - Dose effect of guidewire position in intravascular brachytherapy.
AB  - It has been reported that the dose effects of metallic guidewires are significant
      in intravascular brachytherapy (IVBT) using a beta source. The purpose of this
      work is to investigate the dependence of these dose effects on guidewire
      position. The EGS4 Monte Carlo codes were used to perform the dose calculations
      for the 90Sr (NOVOSTE), 32P (Guidant) and 192Ir (BEST Ind.) sources with and
      without a guidewire in place. Guidewires were placed at various distances from
      the central axes of the sources. Due to the attenuation by the guidewires, a dose
      reduction of up to 70% behind a guidewire was observed for the beta sources,
      while the dose perturbation was found to be negligible for the gamma source. The
      dose reduction for the beta sources was found to be dependent on the guidewire
      location. For example, the dose reduction was 10% higher for a stainless steel
      guidewire located at 0.5 mm than that for the guidewire at 2 mm from the central
      axis of the source, The portion of the target volume affected (shadowed)
      dosimetrically by the guidewire was reduced when the guidewire was positioned
      farther away from the source. The shadow volume (in which the dose reduction
      occurs) can be reduced by up to 45% as the guidewire is moved away from the
      source axis from 0.5 mm to 2 mm. The dosimetric perturbations due to the presence
      of a metallic guidewire as well as their dependence on guidewire location should
      be considered in designing a new IVBT delivery device, in analysing the treatment
      efficacy, and/or in dose prescription for a beta source.

PMID- 12069091
TI  - Voxel effects within digital images of trabecular bone and their consequences on
      chord-length distribution measurements.
AB  - Chord-length distributions through the trabecular regions of the skeleton have
      been investigated since the early 1960s. These distributions have become
      important features for bone marrow dosimetry; as such, current models rely on the
      accuracy of their measurements. Recent techniques utilize nuclear magnetic
      resonance (NMR) microscopy to acquire 3D images of trabecular bone that are then
      used to measure 3D chord-length distributions by Monte Carlo methods. Previous
      studies have shown that two voxel effects largely affect the acquisition of these
      distributions within digital images. One is particularly pertinent as it
      dramatically changes the shape of the distribution and reduces its mean. An
      attempt was made to reduce this undesirable effect and good results were obtained
      for a single-sphere model using minimum acceptable chord (MAC) methods (Jokisch
      et al 2001 Med. Phys. 28 1493-504). The goal of the present work is to extend the
      study of these methods to more general models in order to better quantify their
      consequences. First, a mathematical model of a trabecular bone sample was used to
      test the usefulness of the MAC methods. The results showed that these methods
      were not efficient for this simulated bone model. These methods were further
      tested on a single voxelized sphere over a large range of voxel sizes. The
      results showed that the MAC methods are voxel-size dependent and overestimate the
      mean chord length for typical resolutions used with NMR microscopy. The study
      further suggests that bone and marrow chord-length distributions currently
      utilized in skeletal dosimetry models are most likely affected by voxel effects
      that yield values of mean chord length lower than their true values.

PMID- 12069092
TI  - A non-parametric bootstrap approach for analysing the statistical properties of
      SPECT and PET images.
AB  - Knowledge of the statistical properties of reconstructed single photon emission
      computed tomography (SPECT) and positron emission tomography (PET) images would
      be helpful for optimizing acquisition and image processing protocols. We describe
      a non-parametric bootstrap approach to accurately estimate the statistical
      properties of SPECT or PET images whatever the noise properties in the
      projections and the reconstruction algorithm. Using analytical simulations and
      real PET data, this method is shown to accurately predict the statistical
      properties, including the variance and covariance, of reconstructed pixel values
      for both linear (filtered backprojection) and non-linear (ordered subset
      expectation maximization) reconstruction algorithms.

PMID- 12069093
TI  - Dynamics and interaction of filaments in a computational model of re-entrant
      ventricular fibrillation.
AB  - Ventricular fibrillation (VF) is a lethal cardiac arrhythmia. Re-entry, in which
      action potential wavefronts rotate around filaments, is believed to sustain VF.
      In this study we used a computational model of multiple wavelet fibrillation in
      the thin-walled right ventricle (10 mm thick) and the thicker walled left
      ventricle (16 mm thick) to investigate the effect of tissue thickness and
      initiation protocol on re-entry, and to examine whether filament dynamics and
      interaction in the model could explain why re-entry is both rarely observed and
      short-lived in experimental studies that map electrical activation on the heart
      surface. We found (i) that the density of filaments, the proportion of transmural
      filaments and the proportion of filaments visible on the model surface were all
      higher in the 10 mm simulation, (ii) that the initiation protocol influences the
      rate of filament breakdown but not the number of filaments present after 1 s, and
      (iii) that although many filaments are visible on the surface of the model, the
      majority are visible for less than one rotation. This study shows that tissue
      thickness, geometry and initiation protocol influence electrical activation
      during VF, and that the rapid motion and interaction of filaments result in
      transient appearance of surface re-entry.

PMID- 12069094
TI  - Microwave dielectric measurements and tissue characteristics of the human brain:
      potential in localizing intracranial tissues.
AB  - This study describes the measurements of dielectric properties in the microwave
      range to differentiate various human central nervous structures. Using a vector
      network analyser transmission and reflection coefficients were measured from 500
      MHz to 18 GHz in four human formalin fixed human brains. The positions of the
      electrodes were marked, and the tissue was histologically stained to visualize
      the myelo- and the cytoarchitecture as well as the nerve fibre orientation at the
      electrodes. The profiles of the transmission coefficients showed a characteristic
      minimum peak. In order to describe this peak, a mathematical function was fitted.
      Parameters derived from digital image processing were used to characterize the
      myelo- and cytoarchitecure of the tissue at the electrodes. A multiple regression
      model, with the frequency at the transmission peak minimum as a dependent
      variable and two tissue characteristics at the two electrodes as independent
      variables, showed a multiple regression coefficient of 0.765. A neural network
      model was able to estimate the frequency at the transmission peak minimum from
      the tissue characteristics at the electrode. The measurements of dielectric
      properties are well suited to differentiate distinct intracerebral structures.
      The method could be used for online monitoring of the needle's position during a
      stereotactic intervention in neurosurgery.

PMID- 12069095
TI  - A model to assess SAR for surface coil magnetic resonance spectroscopy
      measurements.
AB  - Surface coils are widely used in magnetic resonance (MR) studies due to their
      superior signal to noise properties. Application of excessive power levels to
      transmit surface coils may result in local tissue damage. A homogeneous muscle
      tissue model for the conservative prediction of surface coil specific absorption
      rate (SAR) is introduced. Based on this model, sequence parameters can be limited
      to provide operational levels within safety guidelines. It is demonstrated that
      this model provides worst-case SAR estimates at MR frequencies of 25.75 MHz and
      63.6 MHz. The dependence of SAR on model structure and geometry is analysed and
      conclusions on the relationship between SAR levels and local anatomy are drawn.
      By making a worst-case assumption for the tissue parameters the model provides
      safe operational levels for all tissue types. Power-demanding proton-decoupled
      31P magnetic resonance spectroscopy experiments are possible based on the SAR
      estimates provided. To date SAR values are calculated for 1 g of tissue. Changes
      in regulations to calculate SAR values for 10 g tissue masses, and the according
      averaging of local SAR over a larger volume, have been proposed by the
      International Electrotechnical Commission. A comparative study shows that up to
      100% more energy may be applied to surface coils if SAR values are determined for
      10 g tissue masses rather than 1 g tissue masses.

PMID- 12069097
TI  - Computation of high-resolution SAR distributions in a head due to a radiating
      dipole antenna representing a hand-held mobile phone.
AB  - SAR distributions in a healthy female adult head as a result of a radiating
      vertical dipole antenna (frequency 915 MHz) representing a hand-held mobile phone
      have been computed for three different resolutions: 2 mm, 1 mm and 0.4 mm. The
      extremely high resolution of 0.4 mm was obtained with our quasistatic zooming
      technique, which is briefly described in this paper. For an effectively
      transmitted power of 0.25 W, the maximum averaged SAR values in both cubic- and
      arbitrary-shaped volumes are, respectively, about 1.72 and 2.55 W kg(-1) for 1 g
      and 0.98 and 1.73 W kg(-1) for 10 g of tissue. These numbers do not vary much
      (<8%) for the different resolutions, indicating that SAR computations at a
      resolution of 2 mm are sufficiently accurate to describe the large-scale
      distribution. However, considering the detailed SAR pattern in the head, large
      differences may occur if high-resolution computations are performed rather than
      low-resolution ones. These deviations are caused by both increased modelling
      accuracy and improved anatomical description in higher resolution simulations.
      For example, the SAR profile across a boundary between tissues with high
      dielectric contrast is much more accurately described at higher resolutions.
      Furthermore, low-resolution dielectric geometries may suffer from loss of
      anatomical detail, which greatly affects small-scale SAR distributions. Thus. for
      strongly inhomogeneous regions high-resolution SAR modelling is an absolute
      necessity.

PMID- 12069096
TI  - Removal of local field gradient artefacts in BOLD contrast imaging of head and
      neck tumours.
AB  - Monitoring of oxygenation in tumours is an important issue in predicting the
      success of anti-cancer treatments such as radiotherapy. Gradient echo (GE)
      imaging sequences can be used for monitoring changes in tumour blood flow and
      oxygenation. However, the application of this method in head and neck tumours is
      hampered by significant artefacts and losses of the MR signal near air-tissue
      interfaces. We investigated the usefulness of a gradient-echo slice excitation
      profile (GESEPI) sequence that should keep the oxygen contrast while recovering
      the signal loss caused by susceptibility artefacts. A tumour model was implanted
      in the neck and in the leg of mice. MR imaging was performed at 4.7 T. GE and
      GESEPI sequences were used for monitoring the blood oxygen level dependent (BOLD)
      contrast after carbogen breathing. The pO2 was also monitored in tumours using an
      OxyLite probe (Oxford Optronics). Using the tumours implanted in the leg, we
      found that the variations of signal intensity after carbogen breathing were
      similarin both sequences. In the tumour implanted in the neck, it was possible,
      using GESEPI sequences, to recover the signal loss caused by susceptibility
      artefacts and to monitor the effect of carbogen-induced changes in the tumour.

PMID- 12069098
TI  - First imaging results obtained with a multimodal apparatus combining low-field
      (35.7 mT) MRI and pulsed EPRI.
AB  - Nuclear magnetic resonance imaging (MRI) provides excellent images of organs and
      is an essential diagnostic tool in the medical field. Electron paramagnetic
      resonance imaging (EPRI) is being increasingly used in the biomedical field
      because of recent hardware advances. We present the first images obtained with a
      low-field (35.7 mT) multimodal apparatus that combines MRI and pulsed EPRI. For
      this purpose, the sample is composed of two sections, one sensitive to MRI and
      the other sensitive to EPRI. The MRI section of the sample is composed of three
      tubes containing 7 ml of a 10 mM CuSO4 water solution. The EPR section of the
      sample is composed of two tubes containing 350 mg of lithium phthalocyanine. The
      EPR image represents the two-dimensional projection of the whole sample and is
      reconstructed from 32 one-dimensional projections by using the Fourier
      reconstruction method. The MRI image is obtained by selecting a sample slice, 10
      mm in thickness, by using a spin-echo sequence and the two-dimensional fast
      Fourier transform. The experimental results obtained with this apparatus show
      that the spatial resolution is better than 1 mm for the MRI section and better
      than 7 mm for the EPRI section. The measured SNR of the MRI and EPRI images were
      about 60 and 160, respectively. A detailed description of the hardware, pulse
      sequences and image reconstruction techniques is reported.

PMID- 12069099
TI  - Ceramide-dependent caspase 3 activation is prevented by coenzyme Q from plasma
      membrane in serum-deprived cells.
AB  - Coenzyme Q (CoQ) is the key factor for the activity of the eukaryotic plasma
      membrane electron transport chain. Consequently, CoQ is essential in the cellular
      response against redox changes affecting this membrane. Serum withdrawal induces
      a mild oxidative stress, which produces lipid peroxidation in membranes. In fact,
      apoptosis induced by serum withdrawal can be prevented by several antioxidants
      including CoQ. Also, CoQ can maintain cell growth in serum-limiting conditions,
      whereas plasma membrane redox system (PMRS) inhibitors such as capsaicin, which
      compete with CoQ, inhibit cell growth and induce apoptosis. To understand how
      plasma membrane CoQ prevents oxidative stress-induced apoptosis we have studied
      the induction of apoptosis by serum withdrawal in CEM cells and its modulation by
      CoQ. Serum-withdrawal activates neutral sphingomyelinase (N-SMase), ceramide
      release and caspase-3-related proteases. CoQ addition to serum-free cultures
      inhibited a 60% N-SMase activation, an 80% ceramide release, and a 50% caspase-3
      activity induced by serum deprivation. Caspase activation dependent on ceramide
      release since C2-ceramide was only able to mimic this effect in 10% foetal calf
      serum cultured cells but not in serum-free cultures. Also, in vitro experiments
      demonstrated that C2-ceramide and ceramide-rich lipid extracts directly activated
      caspase-3. Taken together, our results indicate that CoQ protects plasma membrane
      components and controls stress-mediated lipid signals by its participation in the
      PMRS.

PMID- 12069100
TI  - Coenzyme Q10 depletion is comparatively less detrimental to human cultured skin
      fibroblasts than respiratory chain complex deficiencies.
AB  - The oxidative stress possibly resulting from an inherited respiratory chain (RC)
      deficiency was investigated in a series of human cultured skin fibroblasts
      presenting either ubiquinone depletion or isolated defect of the various RC
      complexes. Taken as an index for superoxide overproduction, a significant
      induction of superoxide dismutase activity was observed in complex V-deficient
      fibroblasts harboring the NARP-mutation in the ATPase 6 gene. Superoxide
      dismutase induction was also noticed, albeit to a lesser extent, in complex II
      deficient fibroblasts with a mutation in the nuclear gene encoding the
      flavoprotein subunit of the succinate dehydrogenase. No sign of oxidative stress
      could be found in ubiquinone-depleted fibroblasts. In all cases but complex IV
      defect, increased oxidative stress was associated with increased cell death. In
      glucose-rich medium, apoptosis appeared as the main cell death process associated
      with all types of RC defect. However, similar to the great variations in
      oxidative stress associated with the various types of RC defect, we found that
      apoptotic features differed noticeably between defects. No indication of
      increased cell death was found in ubiquinone-depleted fibroblasts.

PMID- 12069101
TI  - Mitochondrial superoxide radical formation is controlled by electron bifurcation
      to the high and low potential pathways.
AB  - The generation of oxygen radicals in biological systems and their sites of
      intracellular release have been subject of numerous studies in the last decades.
      Based on these studies mitochondria are considered to be the major source of
      intracellular oxygen radicals. Although this finding is more or less accepted,
      the mechanism of univalent oxygen reduction in mitochondria is still obscure. One
      of the most critical electron transfer steps in the respiratory chain is the
      electron bifurcation at the cytochrome bc1 complex. Recent studies with
      genetically mutated mitochondria have made it clear that electron bifurcation
      from ubiquinol to the cytochrome bc1 complex requires the free mobility of the
      head domain of the Rieske iron-sulfur protein. On the other hand, it has been
      long known that inhibition of electron bifurcation by antimycin A causes leakage
      of single electrons to dioxygen, which results in the release of superoxide
      radicals. These findings lead us to study whether hindrance of the interaction of
      ubiquinol with the cytochrome bc1 complex is the regulator of single electron
      diversion to oxygen. Hindrance of electron bifurcation was observed following
      alterations of the physical state of membrane phospholipids in which the
      cytochrome bc1 complex is inserted. Irrespective of whether the fluidity of the
      membrane lipids was elevated or decreased, electron flow rates to the Rieske iron
      sulfur protein were drastically reduced. Concomitantly superoxide radicals were
      released from these mitochondria, strongly suggesting an effect on the mobility
      of the head domain of the Rieske iron-sulfur protein. This revealed the
      involvement of the ubiquinol cytochrome bc1 redox couple in mitochondrial
      superoxide formation. The regulator, which controls leakage of electrons to
      oxygen, appears to be the electron-branching activity of the cytochrome bc1
      complex.

PMID- 12069102
TI  - Coenzyme Q10: absorption, antioxidative properties, determinants, and plasma
      levels.
AB  - The purpose of this article is to summarise our studies, in which the main
      determinants and absorption of plasma coenzyme Q10 (Q10, ubiquinone) have been
      assessed, and the effects of moderate dose oral Q10 supplementation on plasma
      antioxidative capacity, lipoprotein oxidation resistance and on plasma lipid
      peroxidation investigated. All the supplementation trials carried out have been
      blinded and placebo-controlled clinical studies. Of the determinants of Q10,
      serum cholesterol, serum triglycerides, male gender, alcohol consumption and age
      were found to be associated positively with plasma Q10 concentration. A single
      dose of 30 mg of Q10, which is the maximum daily dose recommended by Q10
      producers, had only a marginal elevating effect on plasma Q10 levels in non-Q10
      deficient subjects. Following supplementation, a dose-dependent increase in
      plasma Q10 levels was observed up to a daily dose of 200 mg, which resulted in a
      6.1-fold increase in plasma Q10 levels. However, simultaneous supplementation
      with vitamin E resulted in lower plasma Q10 levels. Of the lipid peroxidation
      measurements, Q10 supplementation did not increase LDL TRAP, plasma TRAP,
      VLDL+LDL oxidation resistance nor did it decrease LDL oxidation susceptibility ex
      vivo. Q10 with minor vitamin E dose neither decreased exercise-induced lipid
      peroxidation ex vivo nor muscular damage. Q10 supplementation might, however,
      decrease plasma lipid peroxidation in vivo, as assessed by the increased
      proportion of plasma ubiquinol (reduced form, Q10H2) of total Q10. High dose
      vitamin E supplementation decreased this proportion, which suggests in vivo
      regeneration of tocopheryl radicals by ubiquinol.

PMID- 12069103
TI  - Reduction of 1,4-quinone and ubiquinones by hydrogen atom transfer under UVA
      irradiation.
AB  - 1,4-Benzoquinone, coenzyme Q0 and Q10 were reacted with a series of hydrogen
      donors in the ESR cavity in the presence or absence of UVA irradiation. The
      signals of the radicals generated from the hydrogen donors or of those of the
      semiquinones were detected. The reaction mechanism was interpreted by a hydrogen
      atom transfer instead of the usual electron transfer mechanism on the basis of
      the redox potentials of the reactants and the Marcus theory. The hydrogen atom
      transfer is explained by the excited triplet state of quinones, which, on the
      basis of quantum mechanic calculations, may be reached even under visible light.
      In some cases, hydrogen atom transfer was also observed without irradiation,
      although to a lesser extent.

PMID- 12069104
TI  - Regulation of the mitochondrial permeability transition pore by ubiquinone
      analogs. A progress report.
AB  - The permeability transition pore (PTP) is a mitochondrial inner membrane Ca2+
      sensitive channel that plays a key role in different models of cell death. In a
      series of recent studies we have shown that the PTP is modulated by quinones, and
      we have identified three functional classes: (i) PTP inhibitors; (ii) PTP
      inducers; and (iii) PTP-inactive quinones that compete with both inhibitors and
      inducers. Here, we review our current understanding of pore regulation by
      quinones, and present the results obtained with a new series of structural
      variants. Based on the effects of the compounds studied so far, we confirm that
      minor structural changes profoundly modify the effects of quinones on the PTP. On
      the other hand, quinones with very different structural features may have
      qualitatively similar effects on the PTP. Taken together, these results support
      our original proposal that quinones affect the PTP through a common binding site
      whose occupancy modulates its open-closed transitions, possibly through secondary
      changes of the Ca2+-binding affinity.

PMID- 12069105
TI  - Effect of dicumarol, a Nad(P)h: quinone acceptor oxidoreductase 1 (DT-diaphorase)
      inhibitor on ubiquinone redox cycling in cultured rat hepatocytes.
AB  - Ubiquinol is considered to serve as an endogenous antioxidant. However, the
      mechanism by which the redox state of intracellular ubiquinone (UQ) is maintained
      is not well established. The effect of dicumarol, an inhibitor of NAD(P)H:
      quinone acceptor oxidoreductase 1 (NQO1 = DT-diaphorase, EC 1.6.99.2), on the
      reduction of UQ in cultured rat hepatocytes was investigated in order to clarify
      whether or not NQO1 is involved in reducing intracellular UQ. A concentration of
      5 microM dicumarol, which does not inhibit cytosolic NADPH-dependent UQ reductase
      in vitro, was observed to almost completely inhibit NQO1 and thereby to stimulate
      cytotoxicity of 2-methyl-1,4-naphthoquinone (menadione) in cultured rat
      hepatocytes. However, 5 microM dicumarol did not inhibit reduction of endogenous
      UQ-9, as well as exogenous UQ-10 added to the hepatocytes. In addition, it did
      not stimulate the formation of thiobarbituric acid reactive substances (TBARS) in
      the hepatocytes. These results suggested that NQO1 is not involved in maintaining
      UQ in the reduced state in the intact liver cells.

PMID- 12069106
TI  - Coenzyme Q cytoprotective mechanisms for mitochondrial complex I cytopathies
      involves NAD(P)H: quinone oxidoreductase 1(NQO1).
AB  - The commonest mitochondrial diseases are probably those impairing the function of
      complex I of the respiratory electron transport chain. Such complex I impairment
      may contribute to various neurodegenerative disorders e.g. Parkinson's disease.
      In the following, using hepatocytes as a model cell, we have shown for the first
      time that the cytotoxicity caused by complex I inhibition by rotenone but not
      that caused by complex III inhibition by antimycin can be prevented by coenzyme Q
      (CoQ1) or menadione. Furthermore, complex I inhibitor cytotoxicity was associated
      with the collapse of the mitochondrial membrane potential and reactive oxygen
      species (ROS) formation. ROS scavengers or inhibitors of the mitochondrial
      permeability transition prevented cytotoxicity. The CoQ1 cytoprotective mechanism
      required CoQ1 reduction by DT-diaphorase (NQO1). Furthermore, the mitochondrial
      membrane potential and ATP levels were restored at low CoQ1 concentrations (5
      microM). This suggests that the CoQ1H2 formed by NQO1 reduced complex III and
      acted as an electron bypass of the rotenone block. However cytoprotection still
      occurred at higher CoQ1 concentrations (>10 microM), which were less effective at
      restoring ATP levels but readily restored the cellular cytosolic redox potential
      (i.e. lactate: pyruvate ratio) and prevented ROS formation. This suggests that
      CoQ1 or menadione cytoprotection also involves the NQO1 catalysed reoxidation of
      NADH that accumulates as a result of complex I inhibition. The CoQ1H2 formed
      would then also act as a ROS scavenger.

PMID- 12069107
TI  - Ubiquinol and a coenzyme Q reducing system protect platelet mitochondrial
      function of transfusional buffy coats from oxidative stress.
AB  - The conditions under which Coenzyme Q (CoQ) may protect platelet mitochondrial
      function of transfusional buffy coats from aging and from induced oxidative
      stress were investigated. The Pasteur effect, i.e. the enhancement of lactate
      production after inhibition of mitochondrial respiratory chain, was exploited as
      a marker of mitochondrial function as it allows to calculate the ratio of
      mitochondrial ATP to glycolytic ATP. Reduced CoQ10 improves platelet
      mitochondrial function of transfusional buffy coats and protects the cells from
      induced oxidative stress. Oxidized CoQ is usually less effective, despite the
      presence, shown for the first time in this study, of quinone reductase activities
      in the platelet plasma membranes. The addition of a CoQ reducing system to
      platelets is effective in enhancing the protection of platelet mitochondrial
      function from the oxidative stress. The results support on one hand a possibility
      of protection of mitochondrial function in aging by exogenous CoQ intake, on the
      other a possible application in protection of transfusional buffy coats from
      storage conditions and oxidative deterioration.

PMID- 12069108
TI  - Regulatory aspects of coenzyme Q metabolism.
AB  - A number of factors are involved in the regulation of the amount and distribution
      of coenzyme Q in cells and tissues. These factors modify preferentially the
      biosynthetic mechanism in order to keep up an optimal tissue concentration of the
      lipid. The amount of substrate provided by the mevalonate pathway is able to both
      up- and down-regulate the velocity of synthesis. At the translation level,
      regulation occurs by receptor-mediated ligand binding and appears most clearly
      upon treatment with hormones and peroxisomal inducers. There are a number of
      pathophysiological conditions when these mechanisms of regulation are modified
      and explain the decreased coenzyme Q tissue concentrations. It is of considerable
      interest to establish appropriate physiological, hormonal and drug-mediated
      conditions in order to counteract disturbed cellular functions caused by coenzyme
      Q deficiency

PMID- 12069109
TI  - Cellular redox activity of coenzyme Q10: effect of CoQ10 supplementation on human
      skeletal muscle.
AB  - In this paper, we report results obtained from a continuing clinical trial on the
      effect of coenzyme Q10 (CoQ10) administration on human vastus lateralis
      (quadriceps) skeletal muscle. Muscle samples, obtained from aged individuals
      receiving placebo or CoQ10 supplementation (300mg per day for four weeks prior to
      hip replacement surgery) were analysed for changes in gene and protein expression
      and in muscle fibre type composition. Microarray analysis (Affymetrix U95A human
      oligonucleotide array) using a change in gene expression of 1.8-fold or greater
      as a cutoff point, demonstrated that a total of 115 genes were differentially
      expressed in six subject comparisons. In the CoQ10-treated subjects, 47 genes
      were up-regulated and 68 down-regulated in comparison with placebo-treated
      subjects. Restriction fragment differential display analysis showed that over 600
      fragments were differentially expressed using a 2.0-fold or greater change in
      expression as a cutoff point. Proteome analysis revealed that, of the high
      abundance muscle proteins detected (2,086 +/- 115), the expression of 174
      proteins was induced by CoQ10 while 77 proteins were repressed by CoQ10
      supplementation. Muscle fibre types were also affected by CoQ10 treatment; CoQ10
      treated individuals showed a lower proportion of type I (slow twitch) fibres and
      a higher proportion of type IIb (fast twitch) fibres, compared to age-matched
      placebo-treated subjects. The data suggests that CoQ10 treatment can act to
      influence the fibre type composition towards the fibre type profile generally
      found in younger individuals. Our results led us to the conclusion that coenzyme
      Q10 is a gene regulator and consequently has wide-ranging effects on over-all
      tissue metabolism. We develop a comprehensive hypothesis that CoQ10 plays a major
      role in the determination of membrane potential of many, if not all, sub-cellular
      membrane systems and that H2O2 arising from the activities of CoQ10 acts as a
      second messenger for the modulation of gene expression and cellular metabolism.

PMID- 12069110
TI  - Coenzyme Q10 as a possible treatment for neurodegenerative diseases.
AB  - Coenzyme Q10 (CoQ10) is an essential cofactor of the electron transport gene as
      well as an important antioxidant, which is particularly effective within
      mitochondria. A number of prior studies have shown that it can exert efficacy in
      treating patients with known mitochondrial disorders. We investigated the
      potential usefulness of coenzyme Q10 in animal models of Parkinson's disease
      (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). It has
      been demonstrated that CoQ10 can protect against striatal lesions produced by the
      mitochondrial toxins malonate and 3-nitropropionic acid. These toxins have been
      utilized to model the striatal pathology, which occurs in HD. It also protects
      against 1-methyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice. CoQ10
      significantly extended survival in a transgenic mouse model of ALS. CoQ10 can
      significantly extend survival, delay motor deficits and delay weight loss and
      attenuate the development of striatal atrophy in a transgenic mouse model of HD.
      In this mouse model, it showed additive efficacy when combined with the N-methyl
      D-aspartate (NMDA) receptor antagonist, remacemide. CoQ10 is presently being
      studied as a potential treatment for early PD as well as in combination with
      remacemide as a potential treatment for HD.

PMID- 12069111
TI  - Mitochondrial dysfunction in Friedreich's ataxia: from pathogenesis to treatment
      perspectives.
AB  - Friedreich's ataxia (FRDA), the most common inherited ataxia, is an autosomal
      recessive degenerative disorder caused by a GAA triplet expansion or point
      mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin,
      is a widely expressed mitochondrial protein, which is severely reduced in FRDA
      patients. The demonstration that deficit of frataxin in FRDA is associated with
      mitochondrial iron accumulation, increased sensitivity to oxidative stress,
      deficit of respiratory chain complex activities and in vivo impairment of cardiac
      and skeletal muscle tissue energy metabolism, has established FRDA as a "new"
      nuclear encoded mitochondrial disease. Pilot studies have shown the potential
      effect of antioxidant therapy based on idebenone or coenzyme Q10 plus Vitamin E
      administration in this condition and provide a strong rationale for designing
      larger randomized clinical trials.

PMID- 12069112
TI  - Heart hypertrophy and function are improved by idebenone in Friedreich's ataxia.
AB  - Friedreich's ataxia (FRDA) is a neuro-degenerative disease causing limb and gait
      ataxia and hypertrophic cardiomyopathy. It results from a triplet expansion in
      the first intron of the frataxin gene encoding a mitochondrial protein of yet
      unknown function. Cells with low frataxin content display generalized deficiency
      of mitochondrial iron-sulfur cluster-containing proteins, which presumably
      denotes overproduction of superoxide radicals in these organelles. Idebenone, a
      short-chain quinone, may act as a potent free radical scavenger protecting
      mitochondria against oxidative stress. We therefore carried out an open trial of
      idebenone (oral supplementation; 5mg/kg/day) in a large series of FRDA patients
      and followed their left ventricular mass and function. Consistent and definitive
      worsening being observed in the natural course of the disease and cardiac
      hypertrophy having no chance of spontaneous reversal and to be subject to a
      placebo effect, the patient's heart status before and after the treatment was
      used to unambiguously establish the effect of the drug. After six months, heart
      ultrasound revealed more than 20% reduction of left ventricular mass in about
      half of the patients (p < 0.001) and no significant change in the other half.
      Since any measurable reversion of this pathogenic trait is highly significant,
      this demonstrates the efficiency of idebenone in controlling heart hypertrophy in
      FRDA. Owing to the absence of side effects of the drug, idebenone (up to
      15mg/kg/day) should be prescribed for FRDA patients continuously as early as
      possible.

PMID- 12069113
TI  - Lipophilic antioxidants in human sebum and aging.
AB  - Skin surface lipids (SSL), a very complex mixture of sebum mixed to small amounts
      of epidermal lipids, mantle the human epidermis, thus representing the outermost
      protection of the body against exogenous oxidative insults. The present work is a
      systematic and quantitative analysis of upper-chest SSL and their content in
      antioxidants in 100 healthy volunteers, divided into five age groups using TLC,
      HPLC, and GC-MS methods. Further, the effect of exposing SSL in vitro to
      increasing doses of UV irradiation was examined. Straight monounsaturated and
      diunsaturated as well as branched monounsaturated fatty acids of triglycerides
      and pooled fractions were found to be higher at maturity than in childhood and in
      advancing age. Diunsaturated fatty acids were below 3% of the total and
      constituted exclusively of C18:2delta5,8, C20:2delta7,10, C18:2delta9,12.
      Squalene, vitamin E (vit. E) and Coenzyme Q10 (CoQ10) were found to increase from
      childhood to maturity to decrease again significantly in old age. Vitamin E and
      CoQ10 were the only known lipophilic antioxidants present in SSL. In spite of
      their low levels they were found to synergically inhibit the UV induced depletion
      of squalene, cholesterol and of unsaturated fatty acids of SSL. In fact, exposure
      of SSL to increasing amounts of UV irradiation led preferentially to lowering of
      the levels of vit. E and CoQ10. Four minimal erythema dose (MED) (5.6J/cm2) were
      able to deplete 84% vit. E and 70% ubiquinone, and only 13% squalene.
      Diunsaturated and monounsaturated fatty acids as well as cholesterol were
      unaffected even following 10 MED UV exposures, which produced a 26% loss of
      squalene. The same UV dose when applied in the absence of vit. E and CoQ10
      produced a 90% decrease of squalene.

PMID- 12069114
TI  - Structural damage induced by peroxidation may account for functional impairment
      of heavy synaptic mitochondria.
AB  - Coenzyme Q distribution, as well as respiratory chain features, in rat brain
      mitochondria depend on mitochondrial subpopulation, brain region and age. Heavy
      mitochondria (HM) usually display the lowest content of respiratory components
      and the lowest enzymatic activities and it has been suggested that they represent
      the oldest mitochondrial population. In this study, we confirmed that HM are
      considerably compromised in their structure. In fact, HM showed to have the
      highest hydroperoxide content and the most consistent modifications in their
      fatty acid pattern with wide loss of fatty acids (or part of them) in the
      phospholipid moiety. Such situation could explain the typical impairment of HM
      and could support the hypothesis that they represent an old mitochondrial
      population.

PMID- 12069115
TI  - The regulation of COQ5 gene expression by energy source.
AB  - The degree of severity of cardiomyopathy is inversely correlated with tissue
      levels of coenzyme Q (Q), suggesting that Q synthesis may impact the progression
      of the disease. It has been suggested that Q functions as an endogenously
      synthesized anti-oxidant, in addition to regenerating the potent anti-oxidants,
      vitamins E and C. However, very little is known about the mechanisms that
      regulate Q synthesis. Using the simple eukaryote Saccharomyces cerevisiae as a
      model, experiments have been designed to investigate the regulation of Q
      synthesis at the genetic level. To investigate the regulation of COQ5 gene
      expression by energy source, mRNA content was evaluated in yeast cells treated
      with dextrose, glycerol or oleic acid. After 1.5 h, more COQ5 mRNA is produced by
      oleic acid treated cells than by glycerol treated. Experiments performed using
      COQ5 promoter deletion/reporter constructs demonstrate a specific response to
      oleic acid. Additional promoter deletion analysis demonstrates that a non
      fermentable carbon source element is also present, responding to both glycerol
      and oleic acid. The specific oleic acid response appears to be regulated by the
      Rtg family of transcription factors. This family of proteins is required for
      oleic acid-induced expression of genes of beta-oxidation and peroxisomal
      proliferation, and plays an important role in co-ordinating
      mitochondrial/peroxisomal/nuclear communication in response to oleic acid, as
      well as defects in cellular respiration.

PMID- 12069117
TI  - Photodynamic therapy in the treatment of lung and oesophageal cancers.

PMID- 12069116
TI  - High precision focused irradiation in the form of fractionated stereotactic
      conformal radiotherapy (SCRT) for benign meningiomas predominantly in the skull
      base location.
AB  - OBJECTIVE: To present early clinical results of stereotactic conformal
      radiotherapy (SCRT) in patients with benign predominantly skull base meningiomas.
      MATERIAL AND METHODS: Between August 1994 and August 1999, 41 patients with
      benign residual or recurrent meningiomas were treated with SCRT. Thirty-three
      were histologically verified. All patients were immobilized in a GTC stereotactic
      relocatable frame, and underwent a post-contrast CT localization scan with
      additional MRI for fusion in 15 patients. Treatment was delivered on a 6 MV
      linear accelerator using three (12 patients), or 4 (29 patients) non-coplanar
      conformal fixed fields to doses of 50-55 Gy in 30-33 daily fractions. Tumours
      were relatively large with a median gross tumour volume (GTV) of 17.9 cm3 (range
      2.5-183 cm3). RESULTS: At a median follow-up of 21 months (range 6-62 months)
      none of 41 patients have recurred. The current imaging tumour control rate is
      100% at 1 and 3 years. The actuarial survival at 2 years is 100% and 91% at 3 and
      5 years. Following SCRT tumour decreased in size in 9 patients. SCRT was well
      tolerated. Five patients had improvement in vision, and six patients improvement
      in cranial nerve function. Two patients whose planning target volume (PTV)
      included the sella developed hypopituitarism during and at 18 months after SCRT.
      One patient with pre-existing hydrocephalus due to pineal region meningioma
      developed cognitive impairment 7 months after treatment. One patient with
      involvement of the optic nerve had visual deterioration at 18 months.
      CONCLUSIONS: SCRT is a feasible high precision irradiation technique for residual
      and recurrent skull base meningiomas including both small and larger tumours with
      excellent early tumour control and low toxicity. Longer follow-up is necessary to
      demonstrate sustained tumour control and low morbidity of such high precision
      localized method of fractionated irradiation.

PMID- 12069118
TI  - Radical radiotherapy incorporating a brachytherapy boost for the treatment of
      carcinoma of the thoracic oesophagus: results from a cohort of patients and
      review of the literature.
AB  - The optimal treatment for potentially curable carcinoma of the oesophagus
      unsuitable for surgical resection is unresolved. An intraluminal brachytherapy
      boost (ILBT) can be used following external beam radiotherapy (EBRT) with or
      without concurrent chemotherapy (CRT). ILBT increases the dose to the tumour
      volume substantially while reducing the lung dose but the corresponding high dose
      to the oesophageal wall may cause increased complications. We report the outcomes
      of 32 consecutive patients treated with radical radiotherapy. A dose of 45-55 Gy
      in 20-25 fractions with external beam radiotherapy (EBRT) followed by an ILBT
      boost. Earlier in the series a low dose rate (LDR) brachytherapy technique using
      125Iodine seeds delivering a dose of 20-22 Gy at 25-40 cGy/h was used. This was
      later superseded by high dose rate (HDR) treatments delivering 8.5-10 Gy in one
      fraction at 1 cm from the catheter. Patients of age below 76 years, of good
      performance status and with no other medical contraindication were considered for
      concurrent chemotherapy (CRT) using a planned regime of cisplatin (80 mg/m2 day
      1) and 5-flurouracil (1 g/m2 days 1 to 4) in the first and last weeks of
      radiotherapy (13 patients). The EBRT and ILBT were well tolerated but 8/13 (62%)
      patients had dose modifications of chemotherapy in one or both cycles due to
      advanced age, co-morbidity or toxicity. The median follow-up period of surviving
      patients was 37 months (range 35-39) and the median overall survival for the
      whole group was 9 months. The overall survival at 1 year was 34.4% (17.6-51.2%),
      15.6% (2.8-28.4%) at 2 and 3 years. Local recurrence-free survival at 1 year was
      35.3% (15.9-54.7%) and 24.5% (8.3-44.6%) at 2 and 3 years (Fig. 2). Though
      symptom relief was good there were six cases of ulceration, six of stricture and
      two fistulae. Biological equivalent for tumour response (BED Gy,10) and late
      radiation effects (BED Gy3) were calculated for the different radiotherapy
      regimens using equations derived from the linear quadratic model. In this series
      no advantage was found in terms of local control or survival for patients
      receiving radiotherapy doses resulting in a BED Gy10 greater than 75% of the
      maximum. Similarly, no significant increase in complications was noted in those
      patients receiving doses resulting in a BED Gy3 > 75% of the maximum. The merits
      and hazards of the ILBT boost used in radical radiotherapy are discussed and the
      relevant literature reviewed.

PMID- 12069119
TI  - Positron emission tomography (PET)--evaluation of 'indeterminate pulmonary
      lesions'.

PMID- 12069120
TI  - Muscle metastasis as initial manifestation of epidermoid carcinoma of the lung.
AB  - Typical sites of squamous cell carcinoma of lung metastases include liver, brain,
      bones, pulmonary and adrenal glands. In advanced dissemination it can rarely
      involve the skeletal muscle. The patient in this case report was a 46-year-old
      man, with no significant medical history. He was admitted to hospital because of
      a large swelling on his left thigh. Investigations resulted in a diagnosis of
      primary squamous cell carcinoma of the lung. Biopsy of the left great adductor
      muscle produced similar pathology to that of the lung primary. This case report
      describes a skeletal muscle metastasis as the first sign of metastatic disease.

PMID- 12069121
TI  - Spinal cord compression--what are the treatment standards?

PMID- 12069122
TI  - Spinal cord compression--a personal and palliative care perspective.
AB  - Malignant spinal cord compression is recognized as an oncological emergency. In
      spite of this, treatment in the U.K. varies widely from one area of the country
      to another. The reported survey shows that this variation is especially
      noticeable at weekends. Palliative care physicians and clinical nurse specialists
      working in the community are trained in the recognition of cord compression and
      are able to improve the early diagnosis and referral of these patients. In
      addition, they have an essential role in the follow-up of those who remain
      paraplegic.

PMID- 12069123
TI  - Bladder cancer--room for improvement.

PMID- 12069124
TI  - Radical radiotherapy and salvage cystectomy as the primary management of
      transitional cell carcinoma of the bladder. Results following the introduction of
      a CT planning technique.
AB  - The objective of this study was to review the results of our policy of primary
      radiotherapy (RT) and salvage cystectomy for transitional carcinoma (TCC) of the
      bladder in the light of changes in our radiotherapy planning procedure, in
      particular the introduction of CT planning. The case notes of 163 patients
      treated with radical radiotherapy using a CT planning technique were examined.
      The main endpoint for assessment was response at the time of the check cystoscopy
      6 months after the completion of treatment. In addition survival was estimated by
      stage of disease and by response at the time of first cystoscopy. Patterns of
      relapse and time to relapse were analysed. All percentages quoted in the text use
      the initial 163 patients as the denominator. One hundred patients (61%) achieved
      a complete response. The complete response rate was significantly related to T
      stage at presentation being 90% for T1, 75% for T2, and 53% for T3 disease
      respectively. Of these patients 78 remain disease free in the bladder (47%).
      Twenty-two have relapsed in the bladder, of whom 5 have also relapsed at
      metastatic sites. Fifteen patients have relapsed outside the bladder whilst
      remaining disease free within the bladder. At the time of last follow up or death
      from other causes 63 of the 100 patients who had a complete response remained
      disease free with an intact bladder. There were 18 (11%) partial responders.
      Seven of these patients went on to have a cystectomy. Ten remain alive, 7 disease
      free, 4 with intact bladders. In 24 patients (15%) there was no response and
      these patients have all died, the median survival being 10 months. In 21 patients
      (13%) a postradiotherapy cystoscopy was not performed. In all but one patient,
      who was lost to follow up, this was because of progressive disease. The median
      survival of these 20 patients was 6 months. Of the 163 patients 35% are alive and
      well with an intact bladder. If patients dying from other causes are included
      then 42% were rendered disease free. Cause specific survival was significantly
      related to stage of disease at presentation with 5 year actuarial survival being
      87%, 48% and 26%, for T1, T2 and T3 disease respectively. Survival was also
      related to response to treatment at 6 months with 5 year survival being 64%, and
      52% for complete and partial responders respectively. Survival was extremely poor
      for non-responders with only 37.5% surviving 1 year and none 5 years. There was a
      highly significant relationship between response and the development of, and the
      time to developing metastatic disease. Of those who exhibited a response 21%
      developed metastatic disease compared to 78% of non-responders. Salvage
      cystectomy offers the possibility of cure in those who achieve a complete or
      partial response with 42% of such patients being rendered disease free. Results
      however are poor in those who did not respond with all patients dying of their
      disease. Response rates for all stages, and survival for stages T1 and T2 are
      much improved from those previously reported from this centre and compare
      favourably with other published series. These results confirm the place of
      radiotherapy and salvage cystectomy in the management of TCC of the bladder in
      selected patients. In about one-third of patients the desired outcome of curing
      the patient of their cancer with organ preservation is achieved. The prognostic
      significance of cystoscopic response at 6 months and stage at presentation is
      confirmed. The outcome for patients with early stage disease is excellent. The
      relationship between response and the development of metastatic disease would
      suggest that even if these patients had had a primary cystectomy they may have
      fared badly, a conclusion supported by the fact that these results are comparable
      with surgical series. This series supports the role of radiotherapy in the
      management of this disease and suggests that modern RT techniques including CT
      planning have had a beneficial effect on the results of radical radiotherapy.

PMID- 12069125
TI  - Cancer gene therapy: Part 2. Candidate transgenes and their clinical development.

PMID- 12069126
TI  - Rectal cancer: what can we learn from the Dutch TME Study? How will this study
      impact on current practice in the U.K?

PMID- 12069127
TI  - Treatment of classical Kaposi's sarcoma with visceral involvement by weekly
      paclitaxel.

PMID- 12069128
TI  - Pleural to serum CEA ratio in lung adenocarcinoma.

PMID- 12069129
TI  - Metastatic testicular cancer with massive gastrointestinal haemorrhage as initial
      presentation.

PMID- 12069130
TI  - Metastases from glioblastoma multiforme (GBM) are a rare but important event.

PMID- 12069132
TI  - NICE or nasty? National Institute of Clinical Excellence.

PMID- 12069133
TI  - Clinical oncology training in the United Kingdom. Results of the Junior
      Radiologists Forum Clinical Oncology Manpower Questionnaire.

PMID- 12069134
TI  - Radiation therapy for vascular malformations--a changing scene.

PMID- 12069135
TI  - Intracranial dural arteriovenous malformations: results of stereotactic
      radiosurgery in 17 patients.
AB  - AIM: To assess the efficacy of stereotactic radiosurgery (STRS) for the treatment
      of dural arteriovenous fistulae (DAVF). MATERIALS AND METHODS: Between November
      1987 and December 1998, 17 patients with a total of 18 DAVF were treated with
      STRS at the National Centre for Stereotactic Radiosurgery, Sheffield. Clinical
      and radiological data was collected retrospectively from the case notes and
      radiological records. Two neuroradiologists classified the pre-STRS appearance of
      the DAVF using the Borden criteria, and reviewed the follow-up imaging. Up to
      date follow-up was requested from the GPs and referring consultants. RESULTS: In
      retrospect one DAVF had been misdiagnosed and was excluded from the study. The
      remaining 17 DAVF were located at the tentorium (6), cavernous sinus (3), right
      parasellar region (1), floor of left middle cranial fossa (1), midline posterior
      fossa (1), petrous apex (1) and transverse sinus (4). Ten were Borden type I,
      four were type II, three were type III. Follow-up angiography was available for
      13 patients; 10 DAVF were completely obliterated, two showed considerable
      reduction in size, one showed deterioration. Clinical follow-up was available for
      14 of the 16 patients. CONCLUSION: Stereotactic radiosurgery can successfully
      obliterate DAVF with few side effects.

PMID- 12069136
TI  - Update on intrapartum fetal pulse oximetry.
AB  - This article examines the current status of fetal pulse oximetry (FPO) as a means
      of intrapartum assessment of fetal wellbeing. FPO has been developed to a stage
      where it is a safe and accurate indicator of intrapartum fetal oxygenation. In
      general, sliding the FPO sensor along the examiner's fingers and through the
      cervix, to lie alongside the fetal cheek or temple is easy The recent publication
      of a randomised controlled trial (RCT) of FPO versus conventional intrapartum
      monitoring has validated its use to reduce caesarean section rates for
      nonreassuring fetal status. An Australian multicentre RCT is currently underway.
      Maternal satisfaction rates with FPO are high. FPO may be used during labour when
      the electronic fetal heart rate trace is nonreassuring or when conventional
      monitoring is unreliable, such as with fetal arrhythmias. If the fetal oxygen
      saturation (FSpO2) values are < 30%, prompt obstetric intervention is indicated,
      such as fetal scalp blood sampling or delivery FSpO2 monitoring should not form
      the sole basis of intrapartum fetal welfare assessment. Rather, the whole
      clinical picture should be considered.

PMID- 12069137
TI  - Ascertaining women's choice of title during pregnancy and childbirth.
AB  - METHODS: A questionnaire was administered to 958 women attending the antenatal
      clinic at Mercy Hospital for Women, Melbourne, to ascertain their choice of title
      during pregnancy Midwifery, nursing and medical staff (376 in total) were also
      invited to respond to a similar questionnaire. RESULTS: The response rate was
      73.6% from the survey of all women who were overwhelmingly in favour of being
      called 'patient' as their first choice (34%), followed by 'other' (20%) and then
      'mother' (19%). Virtually all women requesting 'other' wished to be called by
      their name. Women wishing to be called 'patient' for first choice did not
      significantly differ from the remainder of the study group in age, gestation,
      number of previous pregnancies, or number of children. When women from the Family
      Birth Centre (FBC) were analysed as a separate group, they had a clear preference
      to be called 'other' (unanimously, by their name) than the general antenatal
      population (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.1, 8.3; p <
      0.0001). The staff survey, with a response rate of 84%, also demonstrated that
      'patient' was the most popular first choice for patient title. Medical staff were
      significantly more likely to choose 'patient' (OR 4.2, 95% CI 2.3, 7.7; p <
      0.0001), though the term 'patient' was the preferred choice of all staff.

PMID- 12069138
TI  - Women's experiences of being screened for gestational diabetes mellitus.
AB  - OBJECTIVE: To assess if women screening positive for gestational diabetes
      mellitus (GDM) will experience a reduction in their quality of life. DESIGN:
      Prospective survey SETTING: Level III teaching hospital with a high-risk
      pregnancy service and neonatal intensive care unit. POPULATION: Pregnant women
      prior to being screened for GDM, after screening and late in pregnancy METHODS:
      Women were surveyed using the six-item short-form of the Spielberger State-Trait
      Anxiety Inventory, Edinburgh Postnatal Depression Scale and Short Form 36 Item
      Health Survey Further questions asked about the mother's perception of health and
      the concern the mother felt for the health of her unborn child, the adequacy of
      information given about the screening tests and its results, adequacy of
      information about the results of the diagnostic OGTT and women's overall
      experiences of being screened. MAIN OUTCOME MEASURES: Anxiety, depression, health
      status, concerns about the health of the baby and perceived health. RESULTS:
      After screening, women screening positive for GDM had lower health perceptions (p
      < 0.05), were less likely to rate their health as 'much better than one year ago'
      (p < 0.05) and were more likely to only rate their health as 'fair' rather than
      'very good' or 'excellent' when compared with women screening negative (p <
      0.01). No differences were found in levels of anxiety, depression or the concern
      women felt about the health of their baby CONCLUSIONS: Screening for GDM had an
      adverse impact on women's perceptions of their own health.

PMID- 12069139
TI  - Antenatal and intrapartum antecedents of cerebral palsy: a case-control study.
AB  - AIM: To identify antenatal and intrapartum factors contributing to the aetiology
      of cerebral palsy (CP). METHODS: A case-control study using moderate/severe cases
      of cerebral palsy identified from the Victorian Cerebral Palsy Register and two
      controls per case identified through the Victorian Perinatal Data Collection
      Unit. RESULTS: A number of previously identified risk factors for CP were
      confirmed in our data. New observations were (in specific sub-groups): protective
      effects of mother's negative Rhesus status, cigarette smoking at the first visit
      and episiotomy and an increased risk of CP associated with an abnormal antenatal
      cardiotocograph. CONCLUSIONS: Although the result of the deliberate investigation
      of specific aspects of the antenatal and intrapartum period identified from a
      pilot study, our new findings must be interpreted with caution as they were not
      all based on specific a priori hypotheses, although some had been examined by
      other investigators. We would encourage their evaluation in other data sets.

PMID- 12069140
TI  - Breastfeeding patterns and return to fertility in Australian women.
AB  - OBJECTIVE: The purpose of this study was to understand the relationship between
      infant feeding patterns and the return of fertility during lactation. DESIGN:
      Mother-infant pairs were followed up prospectively from the first week postpartum
      until the return of two normal menstrual bleeds (as judged by the woman) or
      pregnancy SETTING: This study was conducted in the Sydney and Melbourne areas of
      Australia, and was part of a seven-country research project. SAMPLE: Six hundred
      and twenty-four Australian mother-infant pairs participated in the study METHODS:
      Follow-up interviews occurred in the mothers' homes every two weeks. Mothers
      completed a daily diary record chart of vaginal bleeding and infant feeding, and
      completed a detailed diary card of the time and duration of breastfeeds and the
      frequency and nature of all other feedings once every two weeks. MAIN OUTCOME
      MEASURES The main outcomes of the study were measured as the median duration of
      lactational amenorrhoea and lifetable pregnancy rate during lactational
      amenorrhoea. RESULTS: The median duration of amenorrhoea in the Australian
      breastfeeding women who participated in the study was over 8.5 months.
      Breastfeeding was shown to be an effective method of fertility control in that no
      non-contracepting, sexually active, amenorrhoeic, breastfeeding woman became
      pregnant in the first six months after delivery. Regular supplements commenced on
      average at five months and the Australian women rarely introduced noncaloric
      (water), caloric (juices), or milk-based supplements before this time.
      CONCLUSIONS: This confirmed the Bellagio Consensus and the effectiveness of the
      Lactational Amenorrhoea Method.

PMID- 12069141
TI  - Contrasting views of staff and patients regarding psychosocial care for
      Australian women who miscarry: a hospital based study.
AB  - OBJECTIVES: The objectives of this study were to assess the psychosocial needs of
      women following miscarriage and to describe what changes should be made to
      improve their hospital care. METHODS: One hundred and nine women were asked to
      complete a survey within one month of discharge from hospital following a
      miscarriage. The women were asked to describe their psychosocial needs,
      satisfaction with hospital care and type of follow-up care provided. The women
      also completed the Edinburgh Depression Scale and the General Health
      Questionnaire-12. Forty-three staff were asked questions relating to the
      psychosocial effects of miscarriage on these women, how the hospital experience
      could be improved for women, and barriers to providing adequate psychosocial
      care. RESULTS: Seventy-five per cent of the women felt that their hospital
      experience could have been improved, particularly by a more considerate and
      sensitive attitude from staff. While staff agreed that the hospital experience
      could be better for women, they considered this would be best achieved by the
      provision of counselling, more privacy and additional staff. Results of the
      Edinburgh Depression Scale indicated that 44% of the women were either possibly
      or probably depressed, while the General Health Questionnaire-12 indicated that
      57% were suffering some psychological distress. CONCLUSION: It is clear that
      women and their hospital care givers want to see improvements in the care given
      to women who miscarry However, disagreement exists as to how this improvement can
      be best achieved.

PMID- 12069142
TI  - Intravaginal 400 microg misoprostol for pregnancy termination in cases of
      blighted ovum: a randomised controlled trial.
AB  - OBJECTIVE: To investigate the effectiveness and side effects of intravaginal
      misoprostol 400 micrograms compared with a placebo for facilitating complete
      abortion in cases of blighted ovum. DESIGN: A prospective randomised placebo
      controlled trial. SETTING: Rajavithi Hospital, Thailand between 1 July 1998 and
      31 January 1999. SAMPLE: Fifty-four pregnant women with gestations of up to 12
      weeks whose diagnosis of blighted ovum had been made by transvaginal ultrasound.
      METHODS: The patients were assigned randomly into two equal groups; the study
      group received two tablets of vaginal misoprostol (200 micrograms/tablet), and
      the control group received two tablets of a vaginal placebo. RESULTS: The
      complete abortion rate was significantly higher in the women receiving
      misoprostol (63%) compared with those receiving the placebo (18.5%) (p < 0.05).
      Lower abdominal pain (74.1%) and fever (14.8%) were significantly higher in the
      study group than in the placebo group (22.2%) and (0%) respectively, (p < 0.05).
      CONCLUSION: Intravaginal 400 microg misoprostol is significantly more effective
      for termination of blighted ovum than placebo, but lower abdominal pain and fever
      are signifcantly higher in the misoprostol group.

PMID- 12069143
TI  - The absence of factor V Leiden mutation in Malays with recurrent spontaneous
      abortions.
AB  - OBJECTIVES: The objectives of this study were to investigate the prevalence of
      factor V Leiden mutation in Malay women with recurrent spontaneous abortion and
      to clarify the contribution of the factor V Leiden mutation to recurrent
      miscarriages in these women. DESIGN: A prospective case control study between
      June 1999 and April 2000. SETTING: Hospital University Science of Malaysia,
      Kubang Kerian, Kelantan, and Maternal and Child Health Clinic, Pasir Mas,
      Kelantan, Malaysia. SAMPLES: A total of 46 Malay women with a history of three or
      more first or second trimester miscarriages were studied. The control group
      consisted of 46 parous women without obstetric complications. METHODS: Diagnosis
      of factor V Leiden mutation was made by examination of factor V Leiden allele
      product following Mnl I digestion of factor V Leiden alleles amplified by
      polymerase chain reaction. RESULTS: None of the 46 women with recurrent
      spontaneous abortion carried the mutation. Also, we found no subject carrying the
      factor V Leiden alleles in the control group. CONCLUSION: These results suggest
      that that there is no association between the factor V Leiden mutation and
      recurrent spontaneous abortion in the Malay population.

PMID- 12069144
TI  - Prothrombin G20210A mutation is not associated with recurrent miscarriages.
AB  - OBJECTIVE: To assess the association between prothrombin G20210A mutation and
      recurrent miscarriages. STUDY DESIGN: A literature review was performed in
      Medline identifying articles from 1966 to December 2000. Articles meeting
      inclusion criteria were systematically reviewed and included in a meta-analysis.
      RESULTS: Six trials, all case-controlled, were identified. These trials included
      323 women with recurrent pregnancy loss. The odds ratio (OR) for heterozygous
      prothrombin mutation was 1.9 (95% confidence interval (CI) 0.98-4.14), and for
      homozygous prothrombin mutation was 3.76 (95% CI 0.75-18.77). The OR for
      prothrombin mutation and primary recurrent abortion was 2.19 (95% CI 0.61-7.89)
      and for prothrombin mutation and secondary recurrent abortion was 1.29 (95% CI
      0.2-8.36). CONCLUSION: There is no evidence to support an association of
      prothrombin G20210A mutation with recurrent miscarriages.

PMID- 12069145
TI  - Factors associated with pregnancy or miscarriage after clomiphene therapy in WHO
      group II anovulatory women.
AB  - OBJECTIVES: The present study was designed to determine whether clinical and
      endocrine characteristics assessed on initial screening of normogonadotropic
      oligo/amenorrhoeic infertile patients could predict ovulation and then conception
      and successful live birth or miscarriage. STUDY DESIGN: Retrospective cohort
      study SETTING: Outpatient clinic. POPULATION: Eighty-two consecutive women
      receiving clomiphene citrate (CC) therapy from 1993 to 1998. RESULTS: A
      cumulative conception rate of 67% was reached after six or more CC-induced
      cycles. Patients with failure of ovulation after a full course of CC had more
      severe oligomenorrhoea (p < 0.001) and greater BMI (p < 0.05) at initial
      screening. There was no relationship with levels of LH or androgens. In contrast,
      among women who ovulated in response to CC, conception was associated with less
      frequent periods, and higher basal levels of LH, free testosterone and
      androstenedione. Conceptions with subsequent miscarriage were associated with
      intermediate levels of LH and numbers of spontaneous periods between non
      conception and live births. CONCLUSIONS: These observations are consistent with
      the hypothesis that failure of ovulation after CC is related to different factors
      (overweight and severe oligomenorrhoea) from those that predispose to non
      conception (low basal LH and androgen levels and mild oligomenorrhoea).

PMID- 12069146
TI  - Trends in labour and birth interventions among low-risk women in New South Wales.
AB  - OBJECTIVE: To examine recent trends in obstetric intervention rates among women
      at low-risk of poor pregnancy outcome. DESIGN: Cross-sectional analytic study
      SETTING AND POPULATION: A population of 336,189 women categorised as low-risk of
      a poor pregnancy outcome who gave birth to a live singleton in NSW from 1 January
      1990 to 31 December 1997. MAIN OUTCOME MEASURES: Obstetric intervention rates
      including oxytocin induction and augmentation of labour, epidural analgesia,
      instrumental births, caesarean section and episiotomy METHODS: Trends over time
      were assessed by fitting trend-lines to numbers of births or by trends in
      proportions. Unconditional logistic regression was used to assess the impact of
      epidural analgesia on instrumental birth over time. RESULTS: Rates of operative
      births did not rise despite increases in maternal age and use of epidural
      analgesia. Instrumental births declined over time from 26% to 22% among
      primiparas and 5% to 4% among multiparas. There was also a shift to vacuum
      extraction rather than forceps. Although instrumental birth was strongly
      associated with epidural analgesia, the strength of the association declined over
      the study period, for primiparas from an adjusted odds ratio of 7.2 to 5.2 and
      for multiparas from 13.2 to 10.3. CONCLUSIONS: Increased use of epidural
      analgesia for labour has been a feature of the management of birth at term during
      the 1990s. The decline in the strength of association between epidural analgesia
      and instrumental birth may reflect improved epidural techniques and management of
      epidural labour, and recognition of the adverse maternal outcomes associated with
      forceps and vacuum births.

PMID- 12069147
TI  - Late antenatal carriage of group B Streptococcus by New Zealand women.
AB  - OBJECTIVES: To determine in New Zealand women the prevalence of group B
      Streptococcus (GBS) carriage late in pregnancy and to identify GBS colonisation
      risk factors, antibiotic susceptibility and serotype distribution. DESIGN:
      Prospective, observational study. SETTING: Community and hospital antenatal
      clinics in Wellington and Auckland during 1998-1999. SAMPLE: Convenience sample
      of 240 women between 35-37 weeks gestation. METHODS: Sociodemographic data,
      obstetric details and anogenital swabs were collected from each subject. Swabs
      were inoculated into selective media. GBS isolates underwent serotyping and
      antibiotic susceptibility testing. RESULTS: Two hundred and forty women (9%
      Maori, 11% Pacific) aged 15-41 years were recruited. Fifty-two (22%; 95% CI 17,
      27) were colonised by GBS. Carriage was independently associated with younger age
      (59% < or = 30 years; adjusted OR 3.25; 95% CI 1.53, 6.95) and least social
      deprivation (57% NZ Dep 96 score +/- 3; adjusted OR 1.22; 95% CI 1.06,1.39). All
      GBS isolates were penicillin-susceptible, but resistance to clindamycin (15%) and
      erythromycin (7.5%) was detected and associated with serotype V strains.
      Predominant serotypes were: III (29%), Ia (21%), Ib (20%) and V (20%).
      CONCLUSIONS: Approximately 20% of New Zealand women carry GBS late in pregnancy,
      with young age a major risk factor. Increased risk in the socially advantaged,
      development of resistance to erythromycin and clindamycin, and emergence of new
      GBS serotypes are findings with important implications for prevention strategies
      requiring further confirmation.

PMID- 12069148
TI  - Aboriginal teenage pregnancies compared with non-Aboriginal in South Australia
      1995-1999.
AB  - OBJECTIVE: To compare pregnancy characteristics and outcomes between Aboriginal
      and non-Aboriginal teenagers. DESIGN, SETTING AND POPULATION: A retrospective
      cohort study using the perinatal data collection for South Australian births in
      1995-1999: 449 Aboriginal and 4,625 non-Aboriginal teenagers. METHODS: Comparison
      of socio-demographic and clinical characteristics, using relative risks. MAIN
      OUTCOME MEASURES: Rates of pregnancy, smoking during pregnancy, induction,
      delivery method, preterm and small-for-gestational-age births and perinatal
      mortality RESULTS: Aboriginal teenagers have a pregnancy rate more than twice as
      high as non-Aboriginal, but a smaller proportion of pregnancies are terminated.
      They have pregnancies earlier, are more likely to be single, to smoke during
      pregnancy, to have few antenatal visits, to give birth in a country hospital and
      to have infections and anaemia. They have lower induction and analgesia rates,
      but a higher caesarean section rate. Their babies are more likely to be small-for
      gestational-age and preterm, to have a congenital abnormality, to require special
      and intensive nursery care and stay longer in hospital. While their perinatal
      mortality rate has halved since a decade ago, their neonatal death rate is still
      twice that of non-Aboriginal births. CONCLUSIONS: Aboriginal teenagers need
      special attention. Support in particular is needed for Aboriginal health workers
      in preconceptional counselling and health promotion programs that build the
      capacity of the community, eg concerning proper nutrition during pregnancy,
      smoking cessation, breastfeeding, SIDS prevention, support for early and regular
      attendance for antenatal care in friendly and culturally appropriate
      environments. Outreach services and sexual health services for young Aboriginal
      people also need expansion.

PMID- 12069150
TI  - A prospective study of the short-term outcomes of hysterectomy with and without
      oophorectomy.
AB  - OBJECTIVE: To determine the symptom profile and satisfaction rate for women
      undergoing hysterectomy with and without oophorectomy STUDY DESIGN: Women under
      46 years of age who underwent hysterectomy with (n = 266) and without
      oophorectomy (n = 57) were followed for six months. RESULTS: Satisfaction was
      high at six months. In-hospital complication rates were 28% in Group 1 and 39% in
      Group 2 (p = 0.11). Pelvic pain was reported in more than half the women at six
      weeks. A reduction in constipation, diarrhoea, abdominal and pelvic pain, and
      depression was reported at six months. Quality of sexual function in women did
      not improve. New symptoms of pelvic pain or depression were present at six months
      in more than 16% to 37% of the women. Regrets about loss of fertility were
      increased at six months. CONCLUSIONS: Although levels of satisfaction with the
      procedure of hysterectomy were high, new symptoms and regrets about the loss of
      fertility were commonly reported.

PMID- 12069149
TI  - The anatomy of the perineal membrane: its relationship to injury in childbirth
      and episiotomy.
AB  - BACKGROUND: Episiotomy during childbirth, intended to protect the anal sphincter,
      may fail to do so. Furthermore damage to the anal sphincter complex may occur
      without complete perineal tear. We hypothesise that these particular injuries may
      occur due to posterior displacement of the anus leading to distraction of the
      anal sphincter complex from an anterior attachment to the perineal membrane.
      However, the anatomical basis for this has not been well defined. OBJECTIVE: To
      investigate the relationship between the anal sphincter and the perineal
      membrane. MATERIALS AND METHODS: High-resolution MRI scans of a female cadaver
      perineum were performed. The imaging findings were correlated with the anatomical
      structure identified on dissection and histological examination. RESULTS: The
      perineal membrane was easily identified on MR imaging. Fibres from the perineal
      membrane could be seen to attach to the anal sphincter complex at the apex of the
      perineal body This was confirmed on histological examination and was a deeper
      layer than that of the decussation of the superficial transverse perineal muscle
      with the superficial part of the external anal sphincter. CONCLUSION: The upper
      ano-rectal canal and apex of the perineal body have demonstrable attachment to
      the free margin of the perineal membrane postero-lateral to the lower vagina.
      This attachment would resist posterior displacement of the anal canal.

PMID- 12069151
TI  - A retrospective cohort study comparing microwave endometrial ablation with
      levonorgestrel-releasing intrauterine device in the management of heavy menstrual
      bleeding.
AB  - OBJECTIVE: To compare microwave endometrial ablation (MEA) with a levonorgestrel
      releasing intrauterine device (Mirena) in the management of heavy menstrual
      bleeding. DESIGN: A retrospective cohort study SAMPLE: Thirty-nine women were
      treated with MEA and 23 women with Mirena, in the South East Regional Health
      Service of South Australia during 1998 to 2001; the mean duration of follow-up
      was 14.6 months. MAIN OUTCOME MEASURES: Primary measures included acceptability
      of the treatment process, effectiveness of the treatment, and satisfaction with
      outcomes. Secondary measures included side effects, complications and quality of
      life (using the SF-36). RESULTS: Acceptability of the treatment process and
      satisfaction with outcomes was very high for both procedures. Each treatment led
      to a statistically significant reduction in menstrual bleeding (p < 0.0001) and
      dysmenorrhoea scores (p < 0.002). CONCLUSIONS: There were no statistical
      differences between the two treatments for any of the primary or secondary
      outcome measures assessed. The treatments seem equally effective in the
      management of heavy menstrual loss.

PMID- 12069152
TI  - Failed cervical pregnancy with levonorgestrel containing intrauterine
      contraceptive device.

PMID- 12069153
TI  - Cervical pregnancy successfully treated with a sequential combination of
      methotrexate and mifepristone.

PMID- 12069154
TI  - Antenatal diagnosis of vasa praevia--need for a high index of suspicion.

PMID- 12069155
TI  - Isolated fetal pericardial effusion: case report and review of the literature.

PMID- 12069156
TI  - Caesarean section scar endometriosis: two cases of recurrent disease and a
      literature review.

PMID- 12069157
TI  - Pharmaceutical strategies utilizing recombinant human serum albumin.
AB  - Gene manipulation techniques open up the possibility of making recombinant human
      serum albumin (rHSA) or mutants with desirable therapeutic properties and for
      protein fusion products. rHSA can serve as a carrier in synthetic heme protein,
      thus reversibly carrying oxygen. Myristoylation of insulin results in a prolonged
      half-life because of self aggregation and increased albumin binding. Preferential
      albumin uptake by tumor cells serves as the basis for albumin-anticancer drug
      conjugate formulation. Furthermore, drug targeting can be achieved by
      incorporating drugs into albumin microspheres whereas liver targeting can be
      achieved by conjugating drug with galactosylated or mannosylated albumin.
      Microspheres and nanoparticles of different sizes can, with or without drugs
      and/or radioisotopes, be used for drug delivery or diagnostic purposes. In vivo
      implantation of albumin fusion protein expressing cells encapsulated in HSA
      alginate coated beads showed promising results compared to organoids in rats.
      Chimeric peptide strategy with cationized albumin as the transport can deliver
      drugs via receptor mediated transcytosis through the blood brain barrier. Gene
      bearing, albumin microbubbles containing ultrasound contrast agents can non
      invasively deliver gene after destruction by ultrasound. Various site-directed
      mutants of HSA can be tailor made depending on the application required.

PMID- 12069159
TI  - In vitro characterization of hepatic flavopiridol metabolism using human liver
      microsomes and recombinant UGT enzymes.
AB  - PURPOSE: To assess the contribution of drug metabolism to the variability on
      flavopiridol glucuronidation observed in cancer patients, and to determine the
      ability of all known human UDP-glucuronosyltransferase (UGT) isoforms to
      glucuronidate flavopiridol. METHODS: Inter-individual variation in flavopiridol
      glucuronidation was determined by HPLC using hepatic microsomes from 62 normal
      liver donors. Identification of enzymes capable of glucuronidating flavopiridol
      was determined by LC/MS using human embryonic kidney 293 (HEK293) cells stably
      expressing all sixteen known human UGTs. RESULTS: The major product of the
      flavopiridol glucuronidation reaction in human liver microsomes was FLAVO-7-G.
      High variability (coefficient of variation = 49%) was observed in the
      glucuronidation of flavopiridol by human liver microsomes. In vitro formation of
      FLAVO-7-G and FLAVO-5-G was mainly catalyzed by UGT1A9 and UGT1A4, respectively.
      Similar catalytic efficiencies (Vmax/Km) were observed for human liver microsomes
      (1.6 microl/min/mg) and UGT1A9 (1.5 microl/min/mg). CONCLUSIONS: UGT1A9 is the
      major UGT involved in the hepatic glucuronidation of flavopiridol in humans. The
      data suggests that hepatic glucuronidation may be a major determinant of the
      variable systemic glucuronidation of flavopiridol in cancer patients. The large
      variability in flavopiridol glucuronidation may be due to differences in liver
      metabolism among individuals, as a result of genetic differences in UGT1A9.

PMID- 12069158
TI  - Polymers and gels as molecular recognition agents.
AB  - Synthetic polymers and gels capable of molecular recognition are very useful in
      designing novel intelligent biomaterials. In this article we review the recent
      progress in both theoretical and experimental studies toward making
      heteropolymers and gels with biomimetic properties, specifically in relation to
      protein recognition. Knowledge obtained from protein-folding studies sheds much
      light on our understanding of the heteropolymer behavior. Consequently, it is
      possible to design synthetic heteropolymers with specific structure that can fold
      into unique conformations, form receptor-like cavities and recognize specific
      target molecules. Recent studies towards simplifying the requirement for the
      heteropolymer structures and the polymerization procedures are reviewed.
      Intelligent polymer gels can be designed with new and interesting characteristics
      of molecular imprinting. The results are encouraging for further investigation
      and design of synthetic gels with programmable collapsed structure might be
      achieved.

PMID- 12069160
TI  - Transfer of lipophilic markers from PLGA and polystyrene nanoparticles to caco-2
      monolayers mimics particle uptake.
AB  - PURPOSE: The objective of this study was to evaluate nanoparticle uptake by the
      Caco-2 monolayer model in vitro. Special emphasis was placed on the localization
      and the quantification of the uptake of fluorescently labeled polystyrene and
      poly(lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS: Intracellular
      fluorescence was localized by fluorescence and confocal laser scanning
      microscopy. Particle uptake was quantified either directly, by counting
      internalized nanoparticles after separation from the Caco-2 monolayers, or
      indirectly, by extraction of the lipophilic fluorescence marker. In vitro release
      studies of lipophilic markers from nanoparticles were performed in standard
      buffer systems and buffer systems supplemented with liposomes. RESULTS: Instead
      of uptake of polystyrene and PLGA nanoparticles by Caco-2 monolayers an efficient
      transfer of lipophilic fluorescence markers from nanoparticles into Caco-2 cells
      with subsequent staining of intracellular lipophilic compartments was observed.
      Whereas in standard buffer no release of fluorescent marker from polystyrene and
      PLGA nanoparticles was observed, the release studies using liposome dispersions
      as receiver revealed an efficient transfer of fluorescent marker into the
      liposome dispersion. CONCLUSIONS: The results suggest that the deceptive particle
      uptake is caused by a collision-induced process facilitating the transfer of
      lipophilic fluorescent marker by formation of a complex between the nanoparticles
      and the biomembranes. Diffusion of the marker within this complex into lipophilic
      compartments of the cell strongly affects quantitative evaluation of particle
      uptake.

PMID- 12069161
TI  - The role of glutathione in the permeation enhancing effect of thiolated polymers.
AB  - PURPOSE: To verify or refute the mechanism of permeation enhancement with
      thiolated polymers via GSH by the use of NaFlu as marker for the paracellular
      permeation. METHODS: The capability of 0.5% polycarbophil cysteine conjugate (PCP
      Cys) to reduce 0.02% oxidized glutathione (GSSG) was evaluated via iodometric
      titration in aqueous solution. Glutathione in its reduced form (GSH; 0.1%-0.4%)
      and in combination with 0.5% PCP-Cys were tested for their permeation enhancement
      of sodium fluorescein (NaFlu) and fluorescence labeled bacitracin (bac-FITC) used
      as paracellular markers. Permeation studies across guinea pig duodenum were
      carried out in Ussing-type chambers. Opening of the tight junctions was
      additionally monitored by transepithelial electrical resistance (TEER)
      measurements. RESULTS: PCP-Cys (0.5%) was shown to reduce 22.0%+/-8.2% of GSSG
      (0.02%) to GSH in aqueous solution at pH 7.0 and 37 degrees C within 3 h.
      Permeation of NaFlu was shown to depend on the concentration of GSH. The apparent
      permeability coefficient (Papp) of NaFlu in buffer only was 4.98+/-0.5*10(-6),
      while in the presence of 0.4% GSH a Papp of 9.31+/-0.92*10(-6) was achieved,
      representing an enhancement ratio (R = Papp enhancer system/Papp control) of
      1.86. The combination of GSH (0.4%) with PCP-Cys (0.5%) led to a significant (p <
      0.001) improvement of R for NaFlu up to 2.93 accompanied by a decrease in TEER of
      20.3%+/-1.4%. Incubation of bac-FITC with the same GSH/PCP-Cys combination led to
      an enhancement ratio of 2.06 within 3 h. CONCLUSION: GSH plays an important role
      in the opening of tight junctions of intestinal epithelia. It would appear that
      PCP-Cys is able to reduce GSSG, prolonging the concentration of GSH at the apical
      membrane, resulting in significantly enhanced paracellular transport.

PMID- 12069162
TI  - Structure-activity relationship of reversibly lipidized peptides: studies of
      fatty acid-desmopressin conjugates.
AB  - PURPOSE: To synthesize a series of reversible fatty acid-desmopressin (DDAVP)
      conjugates and to study their structure-activity relationship as anti-diuretic
      drugs. METHODS: Seven fatty acid conjugates of DDAVP were prepared using various
      reversible lipidization reagents as described in our previous reports. All
      products were purified by acid precipitation and/or size-exclusion
      chromatography. Reversed-phase HPLC was used to evaluate their purity and
      lipophilicity. The anti-diuretic efficacy of these fatty acid conjugates was
      assessed in vasopressin-deficient Brattleboro rats. Four selected conjugates,
      i.e., DPA, DPH, DPD and DPP (acetic, hexanoic. decanoic, and palmitic acid
      conjugate, respectively), along with DDAVP itself were used in Caco-2 cell uptake
      studies and their degradation and the regeneration of active DDAVP were
      investigated using an in vitro liver slice metabolic system coupled with a HPLC
      assay. RESULTS: All fatty acid-DDAVP conjugates were more lipophilic than DDAVP
      as examined by HPLC analyses. When cysteine was used as the linker, the capacity
      index (k', a measure of lipophilicity) of the conjugates was linearly correlated
      with the number of carbons in the fatty acid chain. The anti-diuretic activity of
      the conjugates was correlated with the length of the fatty acid chain, with C10
      as the minimal requirement for possessing the enhanced anti-diuretic activity.
      Among the seven fatty acid conjugates, palmitic acid conjugate was the most
      potent DDAVP derivative. Removal of carboxyl group from the cysteine linker
      completely abolished the enhancement of the activity. The extent of cellular
      uptake also positively correlated with the lipophilicity of the conjugates. The
      metabolism of DDAVP, DPH, DPD, and DPP by liver slices all followed first order
      kinetics with half-life of 0.30, 0.01, 0.06 and 3.44 hr, respectively. The
      degradation rates of DPH and DPD in the liver slice incubation were much faster
      than that of DDAVP and therefore an accumulation of regenerated DDAVP in the
      media was observed. In contrast, DPP was metabolized much slower than DDAVP and,
      consequently, no significant accumulation of regenerated DDAVP could be detected.
      CONCLUSION: Conjugation of DDAVP with fatty acids increased the lipophilicity and
      the anti-diuretic activity of this peptide drug. The anti-diuretic activity of
      lipidized DDAVP was dependent on the chain length of the fatty acid, as well as
      the structure of the linker in the conjugate. The preservation and enhancement of
      the in vivo antidiuretic activity of the conjugates is most likely due to a
      combination of an improved pharmacokinetic behavior and a concurrent regeneration
      of active DDAVP in tissues.

PMID- 12069163
TI  - In vivo kinetic analysis of covalent binding between N-acetyl-L-cysteine and
      plasma protein through the formation of mixed disulfide in rats.
AB  - PURPOSE: This investigation was undertaken to study the relationship between
      plasma drug clearance and covalent protein-binding kinetics of N-acetyl-L
      cysteine (NAC). METHODS: NAC was intravenously administered to rats via a bolus
      injection or continuous infusion. Plasma concentrations of protein-unbound and
      total NAC were analyzed using a compartment model, taking into consideration of
      the protein binding process, and the apparent first-order binding and
      dissociation rate constants (kon and koff) were obtained. RESULTS: Plasma total
      NAC after a bolus injection showed biphasic elimination with an inflection point
      at 1 hr. After 1 hr, NAC was largely present in the covalent protein-bound form.
      During the steady state of the infusion, approximately 30%-40% of plasma NAC
      bound with protein covalently. The kon, koff, and the elimination rate constant
      of protein-unbound drug (ke) were 0.23, 0.57, and 4.3 hr(-1). The dissociation
      half-life of NAC from protein estimated from koff was in agreement with the
      elimination half-life of plasma total NAC. This suggests that the dissociation of
      NAC from protein rate-limited the drug elimination in plasma (koff < ke).
      CONCLUSION: We demonstrated that plasma total drug clearance is kinetically
      limited by covalent protein binding. The compartmental model described here is
      useful for analyzing its kinetics in vivo.

PMID- 12069164
TI  - Insulin aspart (AspB28 human insulin) derivatives formed in pharmaceutical
      solutions.
AB  - PURPOSE: To isolate and identify the main insulin aspart (AspB28 human insulin)
      derivatives formed in pharmaceuticals (pH 7.4 at 5 degrees C), to estimate rates
      of formation, and to determine their biologic potencies. METHODS: Insulin aspart
      derivatives have been isolated by reversed-phase high-performance liquid
      chromatography (RP-HPLC), and identified by RP-HPLC, peptide mapping, amino acid
      analysis, mass spectrometry. and N-terminal amino acid sequence analysis.
      RESULTS: The main derivatives formed were isoAspB28, isoAspB3, AspB3, and
      desPheB1-N-oxalyl-ValB2 insulin aspart. At 5 degrees C, the rate constants were
      0.00028/month for isoAspB28 and isoAspB3, 0.00024/month for AspB3, and
      0.00013/month for desPheB1-N-oxalyl-ValB2 derivatives of insulin aspart.
      Unexpectedly, the rate of isomerization of B28 was high compared to the rate of
      B3 deamidation at both 5 degrees C and 45 degrees C. The N-terminal and
      especially the C-terminal of the B-chain are highly flexible, which may explain
      the high rate of isoAspB28 formation and that deamidation of AsnB3 occurs. All
      the derivatives had full in vivo biologic potencies. CONCLUSION: Except for
      isoAspB28 insulin aspart, the main derivatives formed in pharmaceuticals of
      insulin aspart and human insulin at pH 7.4 are similar. They are all fully active
      in vivo. In proteins, flexibility of the polypeptide chain seems more important
      than sequence in the formation of succinimides.

PMID- 12069165
TI  - Lysozyme stability in primary emulsion for PLGA microsphere preparation: effect
      of recovery methods and stabilizing excipients.
AB  - PURPOSE: To investigate the conformational stability of a model protein,
      lysozyme, in the primary emulsion phase of the microsphere preparation process.
      METHODS: The conformational stability of lysozyme during primary emulsification
      was assessed by differential scanning calorimetry (DSC) and enzymatic activity
      assay. PEG 400 was used to separate lysozyme from water-in-oil (w/o) emulsion
      containing poly(lactideco-glycolide) (PLGA). RESULTS: No significant changes in
      the recovery of lysozyme were observed due to increasing sonication time from 20
      to 60 s at 40 W or increasing intensity from 40 to 60 W for 20 s. By using the
      method involving PEG 400, lysozyme recovery in the presence of PLGA was increased
      from 11.8% to 709%. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) increased
      lysozyme recovery from 35% to 70% at low lysozyme concentration (20 mg/ml), and
      from 70% to 77% at high lysozyme concentration (100 mg/ml) in the presence of
      PLGA. Sugars such as trehalose and mannitol failed to increase lysozyme recovery.
      DSC results suggested the retention of the conformational structure of the
      recovered lysozyme, which was supported by an enzymatic activity assay.
      CONCLUSIONS: HP-beta-CD was found to be a promising stabilizer that protected
      lysozyme during the primary emulsification. Protein recovery method with the help
      of PEG 400 allowed the study of protein stability in w/o emulsions in the
      presence of PLGA. DSC provided supplementary information on the conformational
      changes of lysozyme during emulsification.

PMID- 12069166
TI  - Analysis methods of polysorbate 20: A new method to assess the stability of
      polysorbate 20 and established methods that may overlook degraded polysorbate 20.
AB  - PURPOSE: Polysorbate 20 is a commonly used excipient in biopharmaceutical
      formulations, some of which may have an enzymatic activity. The action(s) of
      polysorbate 20 in biopharmaceutical formulations as a stabilizer require this
      surfactant to maintain its intact structure. This manuscript evaluates a new
      analytic method for the analysis of polysorbate 20 degradation in the format of a
      biopharmaceutical formulation and makes a comparison with several established
      methods of analysis. METHODS: Polysorbate 20 samples were degraded in a
      controlled environment utilizing the enzyme pancreatic lipase to generate
      degradants that included lauric acid and the sorbitan polyoxyethylene side chain.
      A new method was developed with sufficient sensitivity to analyze the degraded
      solutions. Lauric acid was derivatized with the fluorescent reagent 9
      anthryldiazomethane to form 9-anthrylmethylethyl ester. The derivatized lauric
      acid was separated by reversed-phase chromatography and detected by fluorescence
      or UV spectroscopy. Three established methods utilized to measure polysorbate 20
      were evaluated for their ability to detect degraded polysorbate 20. These methods
      were: (1) fluorescence analysis with N-phenyl-1-naphthylamine fluorescent dye;
      (2) UV spectroscopy with ammonium cobaltothiocyanate colorimetric reagent; and
      (3) nuclear magnetic resonance (NMR). RESULTS: Polysorbate 20 incubation with
      lipase resulted in degraded polysorbate 20 as determined by the derivatized
      lauric acid assay. The UV spectroscopy assay utilizing ammonium
      cobaltothiocyanate reagent was not able to detect the degradation of polysorbate
      20 in the samples. The fluorescence method of analysis detected polysorbate 20
      degradation as an approximate 50% decrease in micelles in comparison to standard
      nondegraded polysorbate 20 solutions. NMR analysis resulted in similar proton
      peak areas for both degraded and nondegraded polysorbate 20 samples. NMR spectra
      did contain minor differences between the samples. CONCLUSIONS: It is essential
      to choose the appropriate method of polysorbate 20 evaluation to assess the
      content, stability, and compatibility of a formulation. Current established
      methods to assess polysorbate 20 may overlook and do not necessarily monitor the
      potential degradation of this surfactant, which results in the formation of
      lauric acid. Because this type of degradation may occur in a formulation by an
      enzymatically active biopharmaceutical, a new method of analysis has been
      established.

PMID- 12069167
TI  - Influence of polymorphism on the surface energetics of salmeterol xinafoate
      crystallized from supercritical fluids.
AB  - PURPOSE: To characterize the surface thermodynamic properties of two polymorphic
      forms (I and II) of salmeterol xinafoate (SX) prepared from supercritical fluids
      and a commercial micronized SX (form 1) sample (MSX). METHODS: Inverse gas
      chromatographic analysis was conducted on the SX samples at 30, 40, 50, and 60
      degrees C using the following probes at infinite dilution: nonpolar probes (NPs;
      alkane C5-C9 series); and polar probes (PPs; i.e., dichloromethane, chloroform,
      acetone, ethyl acetate, diethyl ether, and tetrahydrofuran). Surface
      thermodynamic parameters of adsorption and Hansen solubility parameters were
      calculated from the retention times of the probes. RESULTS: The free energies of
      adsorption (- deltaG(A)) of the three samples obtained at various temperatures
      follow this order: SX-II > MSX approximately/= SX-I for the NPs; and SX-II > MSX
      > SX-I for the PPs. For both NPs and PPs, SX-II exhibits a less negative enthalpy
      of adsorption (deltaH(A)) and a much less negative entropy of adsorption (ASA)
      than MSX and SX-I, suggesting that the high -AGA of SX-II is contributed by a
      considerably reduced entropy loss. The dispersive component of surface free
      energy (gammas(D)) is the highest for MSX but the lowest for SX-II at all
      temperatures studied, whereas the specific component of surface free energy of
      adsorption (-deltaG(A)SP) is higher for SX-II than for SX-I. That SX-II displays
      the highest -deltaG(A) for the NP but the lowest gammasD of all the SX samples
      may be explained by the additional -AGA change associated with an increased
      mobility of the probe molecules on the less stable and more disordered SX-II
      surface. The acid and base parameters, K(A) and K(D) that were derived from
      deltaH(A)SP reveal significant differences in the relative acid and base
      properties among the samples. The calculated Hansen solubility parameters
      (deltaD, deltap, and deltaH) indicate that the surface of SX-II is the most polar
      and most energetic of all the three samples in terms of specific interactions
      (mostly hydrogen bonding). CONCLUSIONS: The metastable SX-II polymorph possesses
      a higher surface free energy, higher surface entropy, and a more polar surface
      than the stable SX-I polymorph.

PMID- 12069168
TI  - Influence of alkali metal counterions on the glass transition temperature of
      amorphous indomethacin salts.

PMID- 12069169
TI  - High throughput screening of transdermal formulations.
AB  - PURPOSE: Applications of transdermal drug delivery are limited by low skin
      permeability. Many chemicals have been used to enhance skin permeability,
      however, only a handful are actually used in practice. Combinations of chemicals
      are likely to be more efficient in enhancing skin permeability compared to
      individual enhancers. However, identification of efficient enhancer combinations
      is quite challenging because many chemical enhancers interact with each other and
      with the skin in a complex manner. In the absence of a fundamental knowledge of
      such interactions, we need to rely on rapid methods to screen various enhancer
      combinations for their effectiveness. In this paper, we report a novel high
      throughput (HTP) method that is at least 50-fold more efficient in terms of skin
      utilization and up to 30-fold more efficient in terms of holdup times than the
      current methods for formulation screening (Franz diffusion cells). METHODS: A
      high throughput method was developed based on skin conductivity and mannitol
      penetration into the skin. This method was used to perform at least 100
      simultaneous tests per day. Detailed studies were performed using two model
      enhancers, sodium lauryl sulfate (SLS) and dodecyl pyridinium chloride (DPC). The
      predictions of the high throughput method were validated using Franz diffusion
      cells. RESULT: High throughput screening revealed that mixtures of SLS and DPC
      are significantly more effective in enhancing transdermal transport compared to
      each of them alone. Maximum efficiency was observed with near-equimolar mixtures
      of SLS: DPC. The predictions of the HTP method compared well against those made
      using Franz diffusion cells. Specifically, the effect of surfactant mixtures on
      skin conductivity and mannitol permeability measured using Franz cells also
      showed a maximum at near-equimolar mixtures of SLS: DPC. CONCLUSIONS: The novel
      HTP method allows rapid screening of enhancer formulations for transdermal
      applications. This method can be used to discover new and effective enhancer
      mixtures. At the same time, these data may also broaden our understanding of the
      effect of enhancers on skin permeability.

PMID- 12069171
TI  - Utility of MTT assay in three-dimensional cultured human skin model as an
      alternative for draize skin irritation test: approach using diffusion law of
      irritant in skin and toxicokinetics-toxicodynamics correlation.
AB  - PURPOSE: A cytotoxicity assay using a three-dimensional cultured human skin
      model, Living Skin Equivalent-high (LSE-high) was evaluated as an alternative to
      the Draize skin irritation tests using animals. A relation between the
      cytotoxicity and calculated concentration of an irritant in skin was also
      evaluated. METHODS: Colorimetric thiazoyl blue (MTT) conversion assay and a
      surfactant, cetylpyridinium chloride (CPC), were selected as a cytotoxicity assay
      and a model irritant. The fraction of dead cell number in the MTT assay or the
      Draize irritation score (in vitro and in vivo irritation data, respectively) was
      treated as a function of CPC concentration in the viable skin of LSE-high and
      guinea pig. Separately, in vitro permeations of CPC through the LSE-high or
      excised guinea pig skin were determined to calculate the average concentration of
      CPC in the viable skin using the Fickian diffusion theory. The obtained relations
      between the irritation scores and CPC concentration were evaluated by the Emax
      model (Hill equation). RESULTS: CPC concentration showing 50% irritation (IC50)
      was similar for the MTT assay (18.9%) and Draize test (12.3%), and a good
      relationship (r = 0.981) was observed between the fraction of dead cell number
      and the Draize score. In contrast, IC50, 1.32%, for the MTT assay in LSE-high was
      much lower than that using guinea pig skin. We then corrected the results for the
      MTT assay using a ratio of IC50 in guinea pig skin against LSE-high, resulting in
      a good relation between both MTT results in guinea pig skin and LSE-high.
      CONCLUSION: The present results suggest that the MTT assay using LSE-high may be
      utilized as an alternative for the Draize test in animals for evaluating skin
      irritation.

PMID- 12069170
TI  - Transdermal delivery of highly lipophilic drugs: in vitro fluxes of
      antiestrogens, permeation enhancers, and solvents from liquid formulations.
AB  - PURPOSE: Highly lipophilic basic drugs, the antiestrogens AE 1 (log P = 5.82) and
      AE 2 (log P = 7.8) shall be delivered transdermally. METHODS: Transdermal
      permeation of drugs, enhancers, and solvents from various fluid formulations were
      characterized by in-vitro permeation studies through excised skin of hairless
      mice. Furthermore, differential scanning calorimetry (DSC) measurements of skin
      lipid phase transition temperatures were conducted. RESULTS: Transdermal flux of
      highly lipophilic drugs was extraordinarily enhanced by the unique permeation
      enhancer combination propylene glycol-lauric acid (9 + 1): steady-state fluxes of
      AE 1 and AE 2 were as high as 5.8 microg x cm(-2) x h(-1) and 3.2 microg x cm(-2)
      x h(-1), respectively. This dual enhancer formulation also resulted in a marked
      increase in the transdermal fluxes of the enhancers. Furthermore, skin lipid
      phase transition temperatures were significantly reduced by treatment with this
      formulation. CONCLUSION: Transdermal delivery of highly lipophilic drugs can be
      realized by using the permeation enhancer combination propylene glycol-lauric
      acid. The extraordinary permeation enhancement for highly lipophilic drugs by
      this formulation is due to mutual permeation enhancement of these two enhancers
      and their synergistic lipid-fluidising activity in the stratum corneum.

PMID- 12069172
TI  - Massive and selective delivery of lipid-coated cationic lipoplexes of
      oligonucleotides targeted in vivo to hepatic endothelial cells.
AB  - PURPOSE: Previously we reported on massive uptake of liposomes surface-modified
      with negatively charged aconitylated albumin (AcoHSA) by liver sinusoidal
      endothelial cells (EC) in vivo. In the present work we applied this principle for
      the in vivo delivery of antisense oligonucleotides (ODN) to these cells. METHODS:
      Anti ICAM-1 ODN was complexed with the cationic lipid DOTAP and the complex was
      coated by an excess of neutral lipids including a lipid-anchored poly(ethylene
      glycol). Aco-HSA was coupled to the coated cationic lipoplexes (CCLs). Plasma
      disappearance, organ and intrahepatic distribution of Aco-HSA modified CCLs were
      determined in rats, using [3H]-cholesteryl oleyl ether and 32P-labeled ODN as
      markers. RESULTS: The Aco-HSA coupled CCLs were <160 nm in size, contained 1.03+/
      0.35 nmol ODN and 54+/-18 microg Aco-HSA per micromol total lipid. These CCLs
      were rapidly eliminated from plasma, about 60% the injected dose of 3H- or 32P
      label being recovered in the liver after 30 min. Within the liver, the EC
      accounted for two thirds of total liver uptake. Control non-targeted CCLs were
      eliminated very slowly: after 30 min still >90% of the particles was in the
      blood. CONCLUSIONS: Our results demonstrate efficient targeting of antisense ODN
      to EC in vivo, employing plasma-stable coated cationic lipoplexes, surface
      modified with negatively charged albumin. 40% of the injected ODN was delivered
      to the target cells within 30 min.

PMID- 12069173
TI  - Self-assembled hydrogel nanoparticles responsive to tumor extracellular pH from
      pullulan derivative/sulfonamide conjugate: characterization, aggregation, and
      adriamycin release in vitro.
AB  - PURPOSE: To investigate some physicochemical properties of self-assembled
      hydrogel nanoparticles of pullulan acetate (PA) and sulfonamide conjugates, as a
      potential tumor targeting drug carrier responsive to tumor extracellular pH.
      METHODS: A new class of pH-responsive polymers was synthesized by conjugating a
      sulfonamide, sulfadimethoxine (SDM), to succinylated pullulan acetate (coohPA).
      The polymers formed self-assembled PA/SDM hydrogel nanoparticles in aqueous
      media, which was confirmed by fluorometry and field emission-scanning electron
      microscopy. The pH-dependent behavior of the nanoparticles was examined by
      measuring transmittance, particle size and zeta potential. Adriamycin (ADR) was
      tested for loading into and release from the nanoparticles at various pHs.
      RESULTS: The mean diameters of all PA/SDM nanoparticles tested were <70 nm. with
      a unimodal size distribution. The critical aggregation concentrations at pH 9.0
      were as low as 3.16 microg/mL. The nanoparticles showed good stability at pH 7.4,
      but shrank and aggregated below pH 7.0. The ADR release rate from the PA/SDM
      nanoparticles was pH-dependent around physiological pH and significantly enhanced
      below a pH of 6.8. CONCLUSIONS: The pH-responsive PA/SDM nanoparticles may
      provide some advantages for targeted anti-cancer drug delivery due to the
      particle aggregation and enhanced drug release rates at tumor pH.

PMID- 12069174
TI  - Improved lung delivery from a passive dry powder inhaler using an Engineered
      PulmoSphere powder.
AB  - PURPOSE: To assess the pulmonary deposition and pharmacokinetics of an engineered
      PulmoSphere powder relative to standard micronized drug when delivered from
      passive dry powder inhalers (DPIs). METHODS: Budesonide PulmoSphere (PSbud)
      powder was manufactured using an emulsion-based spray-drying process. Eight
      healthy subjects completed 3 treatments in crossover fashion: 370 microg
      budesonide PulmoSphere inhaled from Eclipse DPI at target PIF of 25 L x min(-1)
      (PSbud25), and 50 L x min(-1) (PSbud50), and 800 microg of pelletized budesonide
      from Pulmicort Turbuhaler at 60 L x min(-1)(THbud60). PSbud powder was
      radiolabeled with 99mTc and lung deposition determined scintigraphically. Plasma
      budesonide concentrations were measured for 12 h after inhalation. RESULTS:
      Pulmonary deposition (mean +/- sd) of PSbud was 57+/-7% and 58+/-8% of the
      nominal dose at 25 and 50 L x min(-1), respectively. Mean peak plasma budesonide
      levels were 4.7 (PSbud25), 4.0 (PSbud50), and 2.2 ng x ml(-1) (THbud60). Median
      t(max) was 5 min after both PSbud inhalations compared to 20 min for Turbuhaler
      (P < 0.05). Mean AUCs were comparable after all inhalations, 5.1 (PSbud25), 5.9
      (PSbud50), and 6.0 (THbud60) ng x h x ml(-1). The engineered PSbud powder
      delivered at both flow rates from the Eclipse DPI was twice as efficiently
      deposited as pelletized budesonide delivered at 60 L x min(-1) from the
      Turbuhaler. Intersubject variability was also dramatically decreased for PSbud
      relative to THbud. CONCLUSION: Delivery of an engineered PulmoSphere formulation
      is more efficient and reproducible than delivery of micronized drug from passive
      DPIs.

PMID- 12069175
TI  - Drug disposition viewed in terms of the fractal volume of distribution.
AB  - PURPOSE: (i) Evaluate the predictive performance of the fractal volume of drug
      distribution, v(f), (Pharm. Res.18, 1056, 2001), (ii) develop the concept of the
      fractal clearance, CLf, which is the clearance analogue of v(f), (iii) examine
      the utility of CLf in allometric studies, (iv) develop allometric relationships
      for the elimination half-life, t1/2, and (v) evaluate the use of v(f) and CLf in
      predicting the volume of drug distribution, Vap, clearance, CL, and elimination
      half-life, t1/2. METHODS: Estimates for v(f) of various drugs were obtained and
      correlated with body mass using data only from animal species. A comparison was
      made between the predicted and actual v(f) values for humans. For a variety of
      animal species CLf values were estimated from the equation: [equation: see text].
      The allometric equations developed using CLf were compared with other allometric
      approaches. Allometric equations were also developed for t1/2 utilizing the
      allometric relationships of v(f) and CLf, RESULTS: The predicted estimates of
      v(f) were very close to the actual values and the correlation exhibited favorable
      statistical properties. The values of the allometric exponents for CLf were found
      to be close to 0.75. The predictive performance for CL using the allometric
      equations for CLf in conjunction with the rule of exponents was found to be
      better than the currently considered most accurate allometric approaches. The
      values of the allometric exponents for t1/2 were found to be close to 0.25
      CONCLUSION: The predictive ability of v(f) is high; predictions for Vap based on
      v(f) values are better than the current approaches. CLf expressed a good behavior
      both in prospective and retrospective analysis. The allometric exponents, 0.75,
      0.25 for CLf and t1/2, respectively, agree with the theoretical expected values.

PMID- 12069176
TI  - Transdermal iontophoresis of tacrine in vivo.

PMID- 12069177
TI  - Blunted induction of hepatic CYP4A in TNF (p55-/-/p75-/-) double receptor
      knockout mice following clofibrate treatment.

PMID- 12069178
TI  - Increased IL-10 production and HLA-DR suppression in the lungs of injured
      patients precede the development of nosocomial pneumonia.
AB  - The incidence of nosocomial pneumonia (NP) among injured patients is substantial.
      We hypothesize that traumatic injury induces alterations in local organ effector
      cell function that may predispose the lungs of injured patients to infection. It
      is the objective of this study to compare the systemic and alveolar effector cell
      response to injury and assess the relationship these have to the development of
      NP. Peripheral blood and bronchoalveolar lavage fluid (BAL) were collected from
      10 elective surgery patients (controls) and 16 multitrauma patients at 12, 36,
      and 60 h post-injury. Systemic and alveolar levels of IL-8 and IL-10 were
      measured. CD11b expression on peripheral blood neutrophils (PBN) and alveolar
      neutrophils (AN) and HLA-DR expression on peripheral blood monocytes (PBM) and
      alveolar macrophages (AM) were measured. Alveolar levels of IL-8 and IL-10 were
      significantly higher than systemic levels after injury. HLA-DR expression was
      reduced on both PBM and AM after injury but was lowest on the AM. Six of 16
      patients (38%) developed NP (NP+). There were no differences in cytokine levels
      (IL-8 and IL-10) or effector cell phenotype (CD11b and HLA-DR expression) within
      the systemic circulation of NP+ and NP- patients. In contrast, NP+ and NP-
      patients differed significantly in alveolar cytokine levels and alveolar effector
      cell phenotype. IL-8 was significantly higher in BAL form NP+ patients at all
      time points after injury. Furthermore, alveolar levels of IL-10 decreased in NP-
      patients but increased in NP+ patients. In all patients, AM HLA-DR expression was
      significantly reduced from normal controls 12 h post-injury. In NP-patients, AM
      HLA-DR expression returned to normal 60 h post-injury, whereas in NP+ patients,
      expression remained suppressed. These findings identify distinct trends in local
      organ cytokine production and alterations in effector cell phenotype that precede
      NP. The persistence of reduced HLA-DR expression amidst increasing levels of IL
      10 in NP+ patients suggest that cell-mediated immune function is being
      suppressed. As such, local organ immunosuppression may be responsible for the
      development of nosocomial pneumonia in injured patients.

PMID- 12069179
TI  - Increased hepatosplanchnic inflammation precedes the development of organ
      dysfunction after elective high-risk surgery.
AB  - This study investigated the relationship of the hepatosplanchnic production and
      uptake of inflammatory mediators, hepatosplanchnic perfusion, and outcome during
      major abdominal surgery to evaluate the hypothesis that regional production of
      inflammatory mediators precedes the development of hepatic dysfunction. This
      retrospective analysis of data and blood samples collected during a randomized
      controlled clinical trial included high-risk surgical patients undergoing major
      abdominal surgery in a 24-bed university-afilliated intensive care unit. Patients
      were divided into a subgroup that developed hepatic dysfunction (HD+)
      postoperatively and a subgroup without hepatic dysfunction (HD-). Hepatic vein
      and arterial plasma levels of IL-6, IL-8, s-E-selectin, s-ICAM-1, and the TNF
      receptors 55 and 75 were measured, and the flux was calculated by multiplying the
      difference in hepatic vein minus arterial levels of the mediators by the
      hepatosplanchnic flow. Systemic (thermodilution) and total hepatosplanchnic blood
      flow (using indocyanine green [ICG]-dilution method) and gastric intramucosal pH
      (pHi) were assessed preoperatively, 4, 24, and 36 h postoperatively. Of a total
      of 26 patients, 6 patients developed hepatic dysfunction after their abdominal
      surgery (mean 6 days postoperatively). The number of sepsis-related deaths and
      postoperative days on the ventilator were significantly higher in this group. A
      higher production of IL-8, TNF-receptor-75 and 55 in the hepatosplanchnic area in
      the HD+ subgroups was found, which preceded the development of organ dysfunction
      (P = 0.04, P = 0.02, and P = 0.02, respectively). Moreover, the uptake of s-ICAM
      1 was significantly increased in this subgroup. Furthermore, total
      hepatosplanchnic blood flow was significantly higher and pHi was significantly
      lower in the HD+ group, whereas global hemodynamic data were similar in the two
      subgroups. In conclusion, the development of postoperative organ dysfunction is
      preceded by an increased regional inflammatory response, indicated by an
      increased soluble TNF-receptor shedding and IL-8 production from the
      hepatosplanchnic area together with an increased uptake of s-ICAM-1. Moreover, an
      increased total hepatosplanchnic blood flow with intramucosal acidosis was
      associated with this regional inflammatory response.

PMID- 12069180
TI  - Base deficit does not predict mortality when secondary to hyperchloremic
      acidosis.
AB  - Base deficit has been established as a predictor of mortality and endpoint of
      resuscitation. We hypothesized that in a significant subset of surgical intensive
      care patients, base deficit is secondary to hyperchloremic acidosis, and that
      these patients experience lower mortality than those patients whose base deficits
      are secondary to other causes. Seventy-five consecutive surgical intensive care
      patients with base deficits greater than 2.0 were prospectively studied. The
      etiology of the patients' base deficits was determined by admission laboratory
      data. Patients were divided into those with hyperchloremic acidosis, and those
      with acidosis from other causes. Mortality within these groups was compared by
      Fisher's exact test. Thirty-seven patients (49.3%) had hyperchloremic acidosis.
      Thirty-three patients (46.7%) had lactic acidosis. Three patients (4%) had base
      deficits secondary to ketosis, and two patients (2.6%) had base deficits
      secondary to uremia. There were no significant differences in age, APACHE II
      scores, or volumes of resuscitation between the hyperchloremic group and the
      remaining patients. There were four deaths (10.8%) in the hyperchloremic group
      and thirteen deaths (34.2%) in the remaining patients (P = 0.03). Hyperchloremic
      acidosis resulted from resuscitation with lactated Ringer's solution in 18
      (48.6%) of the hyperchloremic patients. Hyperchloremic acidosis is a common
      etiology of base deficit in the surgical intensive care unit. It is associated
      with lower mortality than base deficit secondary to other causes. Moreover, it is
      frequently induced following resuscitation with lactated Ringer's solution.
      Failure to properly diagnose this subset of acidotic patients may result in
      inappropriate clinical interventions due to the erroneous presumption of ongoing
      tissue hypoxia.

PMID- 12069181
TI  - Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts
      mortality over 3 days.
AB  - Virtually of the all recent therapeutic interventions for treating sepsis have
      failed to improve survival. One potential explanation is that the heterogeneity
      of the immune response to the septic challenge is such that only a portion of the
      patients die as a result of excessive inflammation. The clinical trials lacked
      power because traditional measurements do not accurately identify these patients.
      Previous work has shown that higher levels of interleukin (IL)-6 are found in
      those mice that die from septic peritonitis; therefore, we sought to determine
      whether IL-6 measured 6 h after surgery could predict outcome. Adult, female
      BALB/c mice (n = 79) were subjected to cecal ligation and puncture with a 21
      gauge needle and treated with imipenem in D5W every 12 h for 5 days, resulting in
      a homogenous population at the outset. Six hours after surgery, 20 microL of
      blood was obtained from the tail vein to measure IL-6. Mortality was followed for
      21 days. Overall 3-day survival was 77%, and 21-day mortality was 56%. Plasma IL
      6 levels >2,000 pg/mL were determined to predict mortality within the first 3
      days with a sensitivity of 58% and specificity of 97%. To further refine the
      mortality prediction, body weight and a complete blood count were performed 24
      hours after cecal ligation and puncture. Discriminate analysis indicated that a
      weighted formula combining body mass, lymphocyte, and platelet count would
      predict death with sensitivity of 83% and a specificity of 79%. We tested the
      value of the IL-6 prediction by surgically resecting the cecum in those animals
      with IL-6 > 2000 pg/mL, which resulted in a significant improvement in survival.
      These data demonstrate that IL-6 measured 6 h after injury accurately predicts
      mortality resulting from experimental sepsis. This measurement may be determined
      quickly so that therapy may be targeted only to those individuals at significant
      risk of dying and initiated within sufficient time to be effective.

PMID- 12069182
TI  - Improved survival of TNF-deficient mice during the zymosan-induced multiple organ
      dysfunction syndrome.
AB  - The purpose of the study was to investigate the course of the zymosan-induced
      multiple organ dysfunction syndrome (MODS) in the absence of tumor necrosis
      factor (TNF) in a murine model. Tumor Necrosis Factor-alpha-lymphotoxin-a
      knockout (TNF/LT-/-) mice (n = 36) and wild-type (TNF/LT+/+) mice (n = 36)
      received 40 microg of lipopolysaccharide (LPS) intraperitoneally followed by
      zymosan at a dose of 1 mg/g body weight 6 days later (day 0). Animals were
      monitored daily for body weight and temperature and clinical symptoms. At day 22,
      most of the surviving mice were killed to examine organ weight and histology. A
      small number of animals were followed until day 48. In all animals, zymosan
      induced an acute sterile peritonitis phase followed by an apparent recovery. From
      day 8 onwards the TNF/LT+/+ mice entered a third-MODS-like-phase, characterized
      by loss of body weight, decreased body temperature, and significant mortality. At
      day 22, survival in the TNF/LT-/- mice (92%) was significantly (P = 0.01) higher
      than in the TNF/LT+/+ mice (60%). In addition, average body temperature and
      average relative (vs. weight at day 0) body weight were higher in the TNF/LT-/-
      mice than in the TNF/LT+/+ mice (35.9 degrees C and 100% vs. 33.3 degrees C and
      84%, respectively). However, at this time point, surviving animals from both
      groups showed similar and significant organ damage, indicated by an increase in
      absolute and relative (vs body weight) weight of lung, spleen, and liver (liver
      only in the TNF/LT-/- mice). Moreover, histopathological examination of organs
      from the surviving animals showed a similar degree of microscopic damage in both
      groups. Interestingly, besides mononuclear cells, inflammatory infiltrates in
      lungs and livers of TNF/LT+/+ but not of TNF-/- mice contained neutrophils. In
      conclusion, TNF-deficient mice exhibit significantly improved morbidity and
      mortality during zymosan-induced MODS. However, the absence of TNF does not
      completely protect against MODS in this murine model.

PMID- 12069183
TI  - Resuscitation from hemorrhagic shock with Ringer's ethyl pyruvate solution
      improves survival and ameliorates intestinal mucosal hyperpermeability in rats.
AB  - We previously showed that pretreatment with a solution of ethyl pyruvate in a
      calcium-containing balanced salt solution, Ringer's ethyl pyruvate solution
      (REPS), ameliorates gut mucosal damage in rats subjected to mesenteric
      ischemia/reperfusion. Herein, we sought to test the hypothesis that REPS would be
      beneficial as a post-treatment (i.e., resuscitation fluid) for hemorrhagic shock.
      Anesthetized Sprague-Dawley rats were bled to a mean arterial pressure (MAP) of
      40 mmHg until 40% of shed blood was returned. The animals then were resuscitated
      over 60 min with the remaining shed blood plus twice the shed blood volume as
      either Ringer's lactate solution (RLS) or REPS. In Experiment 1, RLS or REPS was
      then infused for 3 h more (or until death) at 3 mL/kg/h. Read-outs were post
      resuscitation ileal mucosal permeability to fluorescein-labeled Dextran with an
      average molecular mass of 4000 Da (FD4) and survival. Permeability, determined
      just before death (MAP < 40 mmHg) or after 4 h of resuscitation, was assessed
      using an ex vivo everted gut sac technique and is expressed as a clearance
      (nL/cm/min). In Experiment 2, the read-outs were ileal FD4 permeability measured
      at 60 min after starting resuscitation and gut and liver malondialdehyde (MDA)
      formation. FD4 clearance data were logarithmically transformed prior to
      performing statistical analyses. In Experiment 1, 4/8 (50%) of RLS-treated rats
      survived 4 h after resuscitation whereas 7/7 (100%) of REPS-treated rats survived
      (P< 0.05). Ileal FD4 clearances were 105 +/- 30*, 85 +/- 34*, and 38 +/- 7 for
      all rats treated with RLS, surviving rats treated with RLS, and rats treated with
      REPS, respectively (the asterisk indicates P < 0.05 vs. REPS). In Experiment 2,
      ileal FD4 clearances were 71 +/- 13* and 34 +/- 8 for rats treated with RLS and
      REPS (n = 5 each), respectively. Post-resuscitation levels of MDA in the ileum
      and liver were significantly lower in rats treated with REPS as compared with
      RLS. Resuscitation with REPS, a stable and nontoxic antioxidant solution,
      improves survival and ameliorates ileal mucosal permeability in a rat model of
      severe hemorrhagic shock.

PMID- 12069184
TI  - Inducible nitric oxide synthase is not required in the development of endotoxin
      tolerance in mice.
AB  - We investigated the role of inducible nitric oxide synthase (iNOS) in endotoxin
      tolerance, which was induced in mice genetically deficient of iNOS (iNOS-/-) and
      in wild-type littermates. In non-tolerant wild-type mice, endotoxin induced high
      mortality, elevation of plasma levels of nitrite and nitrate, tumor necrosis
      factor a (TNFalpha), and interleukin 10 (IL-10). These events were preceded by
      degradation of inhibitors kappaBalpha (IkappaBalpha) and kappaBI (IkappaBbeta),
      and activation of nuclear factor-kappaB (NF-kappaB) in the lung. Pretreatment of
      wild-type mice with a sublethal dose of endotoxin prior to lethal endotoxin
      administration ameliorated lethality and blunted TNFalpha production, whereas IL
      10, nitrite, and nitrate production was maintained. These events were associated
      with reduction of IKBa degradation and NF-kappaB activation in the lung. The
      kinetics of degradation of IkappaBbeta were also altered. In parallel
      experiments, nontolerant iNOS-/- mice experienced similar mortality after
      endotoxin as nontolerant wild-type mice. Plasma levels of nitrite and nitrate
      were not elevated after lethal endotoxin administration. IL-10 levels were
      significantly reduced in comparison to nontolerant wild-type mice, whereas
      TNFalpha levels were similarly increased. These events were preceded by lesser
      degradation of IkappaBalpha and reduced NF-kappaB activation in the lung.
      Pretreatment of iNOS-/- mice with a sublethal endotoxin ameliorated lethality.
      TNFalpha production was significantly reduced, whereas IL-10 production was
      significantly increased when compared to nontolerant iNOS-/- mice. Degradation of
      IkappaBalpha and activation of NF-kappaB in the lung were not altered by
      endotoxin tolerance, whereas kinetics of IkappaBbeta degradation was only
      delayed. Our data suggests that iNOS is not required for the development of
      endotoxin tolerance, and that other signal transduction pathways, rather than NF
      kappaB, may regulate induction of endotoxin tolerance in the absence of iNOS.

PMID- 12069186
TI  - Trauma/hemorrhagic shock mesenteric lymph upregulates adhesion molecule
      expression and IL-6 production in human umbilical vein endothelial cells.
AB  - Trauma/hemorrhagic shock (T/HS) is associated with significant lung injury, which
      is mainly due to an inflammatory process, resulting from the local activation and
      subsequent interaction of endothelial cells and leukocytes. Adhesion molecules
      expressed by both cell types play a crucial role in the process of neutrophil
      mediated endothelial cell injury. We have previously shown that mesenteric lymph
      duct ligation prevents T/HS-induced lung leukocyte infiltration and endothelial
      injury, suggesting that inflammatory factors originating from the gut and carried
      in the lymph are responsible for the lung injury observed following T/HS. Based
      on these observations, we hypothesized that inflammatory substances in T/HS lymph
      trigger lung injury by a mechanism involving the upregulation of adhesion
      molecules. To test this hypothesis, we examined whether T/HS mesenteric lymph
      induces the expression of E-selectin, P-selectin, and intracellular adhesion
      molecule-1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs).
      Furthermore, because the cytokine IL-6 is an important component of the
      endothelial inflammatory process, we investigated how T/HS lymph affects the
      production of IL-6 by HUVECs. Mesenteric lymph from T/HS rats increased both E-
      and P-selectin, as well as ICAM-1 expression on HUVECS, as compared to
      trauma/sham shock (T/SS) lymph or medium only groups. However, T/HS lymph failed
      to induce the shedding of E-selectin. In HUVECs treated with T/HS lymph, IL-6
      concentrations were higher than HUVECs treated with T/SS lymph. These findings
      suggest that mesenteric lymph produced after hemorrhagic shock potentiates lung
      injury by the upregulation of endothelial cell adhesion molecule expression and
      IL-6 production.

PMID- 12069185
TI  - Globin attenuates the innate immune response to endotoxin.
AB  - Hemoglobin is an endotoxin (lipopolysaccharide; LPS)-binding protein that
      synergistically increases the release of proinflammatory cytokines from the
      innate immune system in response to LPS. It has been suggested that this activity
      of hemoglobin facilitates the recognition of Gram-negative bacteria in a wound,
      thereby maximizing immune efficiency. This synergy may be important to the
      pathogenesis of a broad spectrum of clinical conditions because elevated
      hemoglobin levels frequently are observed in patients after the transfusion of
      red cells, trauma, cardiopulmonary bypass surgery, hemolysis, in addition to
      other disorders. To determine the molecular basis of the specific hemoglobin-LPS
      synergy, in this article we tested the effects of globin itself on macrophage
      responses to LPS. Paradoxically, these studies revealed that globin suppressed
      tumor necrosis factor (TNF) synthesis in LPS-stimulated murine and human
      macrophage cultures. LPS comigrated with globin on non-denaturing electrophoretic
      gels, giving direct evidence for binding. Globin specifically inhibited LPS
      activity in the standard Limulus assay but did not inhibit interleukin-1beta
      mediated TNF synthesis. Iron supplementation of macrophage cultures significantly
      increased interleukin-1beta-induced TNF release. Intraperitoneal administration
      of globin protected mice against both LPS-induced lethality and experimentally
      induced bacterial infection. Thus, the heme-iron moiety of hemoglobin, and not
      the binding of LPS to globin, enhanced macrophage responses to LPS.

PMID- 12069187
TI  - Hypertonic saline improves intestinal mucosa barrier function and lung injury
      after trauma-hemorrhagic shock.
AB  - Our objective was to test the hypotheses that small volume hypertonic saline
      (HTS) resuscitation protects against trauma-hemorrhagic shock (T/HS)-induced
      intestinal and lung injury better than standard volume resuscitation with
      Ringer's lactate (RL), and that the degree of lung injury correlates with the
      degree of gut injury after therapy. Male Sprague-Dawley rats were subjected to
      laparotomy (trauma) and 90 min of T/HS or sham shock (T/SS), and were then
      resuscitated with RL or 7.5% NaCl solution at an equivalent sodium load.
      Intestinal and lung injury was assessed at 3 and 24 h after resuscitation. Lung
      permeability, pulmonary myeloperoxidase (MPO) levels, and the bronchoalveolar
      lavage fluid (BALF) protein to plasma protein ratio were increased after T/HS,
      but were significantly lower in HTS-resuscitated than RL-treated rats. The
      incidence of bacterial translocation (BT) was not different between the groups,
      but the magnitude of BT after T/HS was less after HTS than RL resuscitation.
      Barrier function of intestinal segments was impaired only in the T/HS rats
      resuscitated with RL and histological analysis demonstrated fewer injured villi
      in the T/HS rats resuscitated with HTS than RL. Linear regression analysis
      revealed direct correlations between the percent of injured villi, increased lung
      permeability, and pulmonary neutrophil sequestration. Resuscitation with HTS
      ameliorated T/HS-induced gut and lung injury seen with RL resuscitation. These
      results, together with the direct correlation found between gut and lung injury,
      suggest that lung injury after T/HS may be mediated by gut injury.

PMID- 12069188
TI  - Tissue damage of non-heart-beating donor lungs after long-term preservation:
      evaluation of histologic alteration, bronchoalveolar lavage, and energy
      metabolism.
AB  - Several studies have shown that warm ischemia before short-term preservation of
      pulmonary grafts from non-heart-beating donors (NHBD) induced morphological
      changes, but still provided a good pulmonary graft function. The aim of this
      study was to investigate morphological and metabolic changes of NHBD lungs after
      long-term preservation. Left lung allotransplantation was performed on 12 native
      bred pigs. In the NHBD group, lungs were subjected to 90 min of warm ischemia
      before harvesting, whereas lungs in the HBD group were harvested immediately
      after cardiac arrest. After a total ischemic period of 19 h, lungs were
      reperfused and pulmonary gas exchange was assessed. Bronchoalveolar lavage (BAL)
      and tissue specimen for wet-to-dry weight (W/D) ratio, histologic examination,
      and measurement of high-energy phosphates were taken 5 h after reperfusion. All
      parameters were compared with a sham-operated control group. Five hours after
      reperfusion, mean paO2 and paCO2 were 288 +/- 52 and 48 +/- 0.8 mmHg,
      respectively, during isolated ventilation of the pulmonary graft with 100% oxygen
      in the NHBD group. W/D ratio and high-energy phosphates of the pulmonary graft
      did not differ between our study groups. Histologic examination showed
      significant morphological changes in the HBD and NHBD group, but alterations were
      more pronounced in the NHBD group. The percentage of neutrophils, total protein
      content, and potassium concentration were significantly elevated in the BAL fluid
      of the NHBD group. Despite the observed aggravation of cellular injury after long
      term preservation, NHBD lungs still performed a good pulmonary graft function.

PMID- 12069189
TI  - Mechanisms of platelet-neutrophil interactions and effects on cell filtration in
      septic shock.
AB  - ABSTRACT-We examined the mechanisms and the adhesive molecules mediating platelet
      neutrophil adhesion in patients with septic shock. Neutrophils, platelets, and
      platelet poor plasma (NPPP) were isolated from 12 normal volunteers. Platelets
      and neutrophils were stimulated with platelet poor plasma (SPPP) removed from 12
      patients in septic shock. Cell adhesion was assessed by filtration through 5
      microm pore filters and by flow cytometry. Blocking monoclonal antibodies were
      used against the platelet and neutrophil surface receptors glycoprotein complex
      IIb/IIla, P-selectin, ICAM-2, CD11a, CD11b, and CD18. The filtration pressure
      (Pi) of cells suspended in SPPP was significantly greater than that of cells
      suspended in NPPP (24 +/- 1.0 mmHg vs. 14 +/- 1.0 mmHg; P< 0.05). The difference
      between the Pi of cells suspended in SPPP or NPPP (deltaPi SPPP-NPPP) in the
      presence of monoclonal antibodies anti-CD41, anti-CD62P, abciximab, anti-CD11a,
      anti-CD11b, and anti-CD18 was significantly less than the APi SPPP-NPPP of cell
      suspensions without the addition of these monoclonal antibodies (P < 0.01). The
      greatest reduction in Pi occurred when platelet receptor P-selectin was blocked
      simultaneously with the CD11b receptor on the neutrophil as compared to all other
      single blocking monoclonal antibodies or combinations of monoclonal antibodies.
      The mean fluorescence of activated platelet CD63-PE binding to neutrophils
      suspended in SPPP was significantly greater than that of cells suspended in NPPP
      (780 +/- 130 Ifu vs. 295 +/- 35 Ifu; P < 0.05). The greatest attenuation in mean
      fluorescence occurred by blocking the P-selectin receptor on the platelet
      simultaneously with CD11b receptor on the neutrophil. We conclude that platelet
      neutrophil aggregation is increased in septic shock. This aggregation is mediated
      by the interaction of multiple platelet and neutrophil surface receptors. The
      platelet receptor P-selectin and the neutrophil receptor CD11b/CD18 appear to
      play the most important role in these interactions.

PMID- 12069190
TI  - CXC chemokine expression after stimulation with interferon-gamma in primary rat
      hepatocytes in culture.
AB  - Monokine-induced by gamma interferon (MIG) and gamma-interferon-inducible protein
      (IP-10) are members of the CXC chemokine family that have been shown to be
      induced by interferon-gamma (IFNy) in some cell types. The purpose of this
      investigation was to determine whether IFNgamma influences CXC chemokine
      production, particularly MIG and IP-10, in primary rat hepatocytes in culture.
      Previous experiments in our laboratory have demonstrated that pharmacologic doses
      of IFNgamma in an in vivo model of hepatic ischemia/reperfusion-induced liver
      injury resulted in increased hepatic levels of IP-10 and MIG and decreased
      hepatic levels of macrophage inflammatory protein-2, Kupffer cells, and
      epithelial neutrophil-activating protein, with a concomitant decrease in
      neutrophil-mediated hepatic injury. In the current investigation, MIG and IP-10
      mRNA and protein were up-regulated in primary rat hepatocytes in vitro in
      response to IFNgamma. Although MIG and IP-10 mRNA were both somewhat increased at
      early time points, larger increases in these chemokines were seen at later time
      points, specifically at 24, 48, and 72 h of incubation as compared to controls.
      Levels of Kupffer cells and macrophage inflammatory protein-2 mRNA after IFNgamma
      were negligible and similar to those seen in controls. These findings were
      confirmed by enzyme-linked immunosorbent assay analysis. These studies
      demonstrate that IFNgamma in vitro up-regulates the production of MIG and IP-10,
      at both the mRNA and protein levels.

PMID- 12069191
TI  - Effects of mild hypothermia on survival and serum cytokines in uncontrolled
      hemorrhagic shock in rats.
AB  - Previous studies have suggested benefit of mild hypothermia during hemorrhagic
      shock (HS). This finding needs additional confirmation and investigation into
      possible mechanisms. Proinflammatory cytokines are mediators of multiple organ
      failure following traumatic hemorrhagic shock and resuscitation. We hypothesized
      that mild hypothermia would improve survival from HS and may affect the pro- and
      anti-inflammatory cytokine response in a rat model of uncontrolled HS. Under
      light halothane anesthesia, uncontrolled HS was induced by blood withdrawal of 3
      mL/100 g over 15 min followed by tail amputation. Hypotensive (limited) fluid
      resuscitation (to prevent mean arterial pressure [MAP] from decreasing below 40
      mmHg) with blood was started at 30 min and continued to 90 min. After hemostasis
      and resuscitation with initially shed blood and Ringer's solution, the rats were
      observed for 72 h. The animals were randomized into two HS groups (n = 10 each):
      normothermia (38 degrees C +/- 0.5 degrees C) and mild hypothermia (34 degrees C
      +/- 0.5 degrees C) from HS 30 min until resuscitation time (RT) 60 min; and a
      sham group (n = 3). Venous blood samples were taken at baseline, RT 60 min, and
      days 1, 2, and 3. Serum interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis
      factor (TNF)-alpha concentrations were quantified by ELISA. Values are expressed
      as median and interquartile range. Survival time by life table analysis was
      greater in the hypothermia group (P = 0.04). Survival rates to 72 h were 1 of 10
      vs. 6 of 10 in the normothermia vs. hypothermia groups, respectively (P = 0.057).
      All cytokine concentrations were significantly increased from baseline at RT 60
      min in both HS groups, but not in the shams. At RT 60 min, in the normothermia
      vs. hypothermia groups, respectively, IL-1beta levels were 185 (119-252) vs. 96
      (57-135) pg/mL (P = 0.15); IL-6 levels were 2242 (1903-3777) vs. 1746 (585-2480)
      pg/mL (P = 0.20); TNF-alpha levels were 97 (81-156) vs. 394 (280-406) pg/mL (P=
      0.02); and IL-10 levels were 1.7 (0-13.3) vs. 15.8 (1.9-23.0) pg/mL (P = 0.09).
      IL-10 remained increased until day 3 in the hypothermia group. High IL-1beta
      levels (>100 pg/mL) at RT 60 min were associated with death before 72 h (odds
      ratio 66, C.I. 3.5-1255). We conclude that mild hypothermia improves survival
      time after uncontrolled HS. Uncontrolled HS induces a robust proinflammatory
      cytokine response. The unexpected increase in TNF-alpha with hypothermia deserves
      further investigation.

PMID- 12069192
TI  - Circadian rhythm of cytokine secretion following thermal injury in mice:
      implications for burn and trauma research.
AB  - Although there are many reports of circadian variation in hormone secretion,
      there are only a few reports on the relationship between circadian rhythm and
      cytokine production. The aim of the present studies was to investigate whether
      there is a circadian effect on cytokine production of splenic lymphocytes and
      adherent splenocytes in mice after burn or sham injury. We selected day 7 after
      injury for our determinations because we have previously shown day 7 is the time
      of maximal suppression of T cell IL-2 and IFNgamma production and maximal
      increase in adherent cell proinflammatory cytokine secretion in this model. IL-2
      and TNFalpha were chosen as reference cytokines since the former is known to be
      produced by T cells and the latter by adherent cells of the innate immune system.
      The results showed that seven days after sham or thermal injury both T cell IL-2
      and adherent cell TNFalpha production were altered by time of injury or time of
      cell harvest. IL-2 secretion was significantly decreased in burn compared to sham
      animals when splenocytes were harvested in the morning; the decrease was non
      significant when splenocytes were harvested in the afternoon. TNFalpha secretion
      was significantly increased in burn vs. sham adherent cells only when injury took
      place in the morning. The observed circadian variations in cytokine production
      could have a significant effect on cytokine levels measured in clinical and
      animal studies of injury and may explain some of the reported discrepancies among
      these studies.

PMID- 12069193
TI  - Development of environmentally friendly syntheses: use of enzymes and biomimetic
      systems for the direct carboxylation of organic substrates.
AB  - Carboxylation reactions widely occur in nature by the direct use of carbon
      dioxide or hydrogen carbonate and are mediated by enzymes, which may or may not
      have a metal as an active center. Such direct carboxylation reactions have found
      only very few applications for synthetic purposes at industrial level. In this
      paper we review a part of the work we have done on the use of carbon dioxide and
      describe: (i) the use of a carboxylation enzyme for the conversion of phenol into
      4-OH benzoic acid; and (ii) the potential of biomimetic mixed anhydrides for the
      synthesis of compounds of industrial interest. The enzymatic production of acetic
      acid from carbon dioxide is compared with known and new transition metal
      catalyzed reactions that are fully biomimetic.

PMID- 12069194
TI  - Recent progress in artificial receptors for phosphate anions in aqueous solution.
AB  - Phosphate esters exist ubiquitously in nature in the form of nucleoside
      phosphates (nucleotides) as components of RNA (or DNA), sugar nucleotides for
      glycosylation of oligosaccharides or proteins, activated form of proteins
      responding to extracellular signals, and chemical mediators playing central roles
      in intracellular signaling signals. Phosphorylation of anti-viral nucleoside
      analogues by intracellular kinases yields nucleoside phosphates (nucleotide) as
      biologically active forms as anti-viral agents. Development of artificial
      phosphate receptors would afford new methodologies for detection, separation, or
      transport of biologically important phosphates. Herein, a recent progress of
      artificial phosphate receptors is reviewed with special focus on macrocyclic
      polyamines and their metal complexes as a new prototype. In comparison to most of
      the previous artificial receptors (most of them are organic molecules), our
      system characteristically works in aqueous solution at neutral pH with extremely
      strong affinities with phosphate anions. Moreover, zinc(II)-macrocyclic
      tetraamine (cyclen) complexes were discovered to selectively bind thymine and
      uracil, so that nucleotides of these bases are specifically recognized by the
      bis(Zn2+-cyclen) complexes.

PMID- 12069196
TI  - Copper-containing monooxygenases: enzymatic and biomimetic studies of the O-atom
      transfer catalysis.
AB  - This review reports our recent studies or the mechanism of O-atom transfer to a
      benzylic C-H bond promoted by Dopamine beta-Hydroxylase (DBH) and its biomimetic
      models. We demonstrate that it is possible to carry out parallel and comparative
      studies on this enzyme (DBH) and its biomimetic models with the same substrate: 2
      aminoindane (3). It was chosen because its two stereogenic centers, both in
      benzylic positions, make it very powerful for studying the stereochemistry of an
      O-atom transfer reaction. DBH-catalyzed hydroxylation of 3 produced exclusively
      14% of trans-(1S,2S)-2-amino-1-indanol (4) (93% ee). Studies with
      stereospecifically deuterium-labeled 2-aminoindanes (1R,2S)-3b and (1S,2S)-3a
      showed that the formation of 4 was the rcsult of an overall process with
      retention of configuration where an O-atom is stereospecifically inserted in the
      trans pro-S position of the substrate. With copper(I) and (II) complexes of
      IndPY2 ligands we studied the reaction with dioxygen and observed an O-atom
      transfer to a benzylic C-H bond which was performed in the same manner as that of
      DBH. With the deuterium-labeled cis-2-d-IndPY2 ligand, we demonstrated that the
      reaction occurs by a stereospecific process with retention of configuration. In
      both cases (enzymatic vs. biomimetic) the O-atom transfers occur in a two-step
      process involving radical intermediates.

PMID- 12069195
TI  - Metal-mediated reactions modeled after nature.
AB  - The Collaborative Research Center (CRC) 436 'Metal-Mediated Reactions Modeled
      after Nature' was founded for the express purpose of analyzing the catalytic
      principles of metallo-enzymes in order to construct efficient catalysts on a
      chemical basis. The structure of the active center and neighboring chemical
      environment in enzymes serves as a focal point for developing reactivity models
      for the chemical redesign of catalysts. Instead of simply copying enzyme
      construction, we strive to achieve new chemical intuition based on the results of
      long-lasting natural evolution. We hope for success, since nature uses a limited
      set of building blocks, whereas we can apply the full repertoire of chemistry.
      Key substrates in this approach are small molecules, such as CO2, O2 NO3- and N2.
      Nature complexes these substrates, activates them and performs chemical
      transformations--all within the active center of a metalloenzyme. In this
      article, we report on some aspects and first results of the Collaborative
      Research Center (CRC) 436, such as nitrate reductase, sphingolipid desaturase,
      carbonic anhydrase, leucine aminopeptidase and dopamine beta-monooxygenase.

PMID- 12069197
TI  - Unsuspected uterine carcinosarcoma (heterologous) diagnosed following
      conservative therapies with medroxyprogesterone acetate for presumed early-stage
      endometrial carcinoma.

PMID- 12069198
TI  - Autoimmune hepatitis complicated with antiphospholipid syndrome in pregnancy.
AB  - PROBLEM: There are few reports on the association between autoimmune hepatitis
      (AIH) and antiphospholipid syndrome; only five reports were found on a MEDLINE
      search between 1966 and 2001. Therefore, the etiology and the optimal treatment
      of them are not clear. METHOD OF STUDY: We encountered a case of AIH complicated
      by antiphospholipid syndrome in pregnancy. We present the clinical course and
      treatment of this case, and discuss some problems in managing such a patient.
      RESULTS: The patient received low-dose prednisolone and low-dose aspirin and
      delivered a live-born infant at term without any adverse effects. CONCLUSION: In
      this case, there was no relation between the variation of alanine
      aminotransferase (ALT) and the one of beta2-glycoprotein I (GPI)-dependent
      anticardiolipin antibody. It is supposed that there was no relation between the
      activity of AIH and the one of antiphospholipid syndrome, and it is also supposed
      that one is not secondary to the other.

PMID- 12069199
TI  - Diversity of antisperm antibodies bound to sperm surface in male immunological
      infertility.
AB  - PROBLEM: The presence of antisperm antibodies (ASA) in males can reduce
      fecundity, however, relationship between the two is disputed. This study was
      performed to investigate if there is diversity of ASA bound to sperm surface
      using immunobead test (IBT) combined with complement dependent sperm
      immobilization test (SIT). METHODS: The ASA bound to sperm surface were detected
      using the direct IBT (D-IBT) in 275 semen samples. In some cases with ASA
      detected by D-IBT, sperm immobilizing antibodies bound to sperm surface were also
      evaluated using direct SIT (D-SIT). RESULTS: The incidence of the immunoglobulin
      G (IgG), IgA, and IgM classes of ASA detected by D-IBT were 2.5, 1.8, and 0.4%,
      respectively. Totally, nine (3.3%) infertile men had ASA on the sperm surface. D
      SIT was tested positive in four (66.7%) of six cases with ASA assessed by D-IBT.
      CONCLUSIONS: Some of the sperm-bound antibodies are associated with complement
      dependent sperm immobilizing antibodies, indicating that there exists a
      heterogeneity of sperm-bound antibodies. This result might be one of the reasons
      for the controversy about the relationship between ASA and immunological
      infertility in men.

PMID- 12069201
TI  - Spontaneous secretion of interleukin-4, interleukin-10 and interferon-gamma by
      first trimester decidual mononuclear cells.
AB  - PROBLEM: A T-helper cell type 2 (Th2) cytokine dominated microenvironment has
      been predicted to be crucial for successful pregnancy. However, little
      information is available about local cytokine secretion in the human decidua. We
      determined the spontaneous secretion of interleukin-4 (IL-4), interferon-gamma
      (IFN-gamma) and IL-10 by decidual mononuclear cells at the single cell level and
      compared it with their secretion by peripheral blood mononuclear cells (PBMC) in
      the first trimester of pregnancy. METHODS OF STUDY: The cytokine secretion from
      decidual and blood cells was detected by a sensitive enzyme-linked immunosorbent
      spot-forming cell (ELISPOT)-assay. RESULTS: Cells secreting IL-4 (median 153,
      range 8-530), IL-10 (median 188, range 32-1600) and IFN-gamma (median 123, range
      15-1140) were detected in all decidual and blood samples. The cytokine secretion
      showed a co-linear pattern in both the blood and decidua, i.e. when one cytokine
      was secreted at high levels, the others followed the trend. No correlation was
      found between the number of cytokine secreting cells in blood and decidua for any
      of the cytokines. CONCLUSIONS: Interleukin-4 and IL-10 are locally secreted in
      the decidua early during normal pregnancy, probably counteracting the fetal
      rejecting effects of co-expressed IFN-gamma. The cytokine secretion by blood
      cells does not generally reflect the local secretion pattern during first
      trimester pregnancy.

PMID- 12069200
TI  - Vitamin A deficiency during rat pregnancy alters placental TNF-alpha signalling
      and apoptosis.
AB  - PROBLEM: Vitamin A is important for immune function and deficiency is associated
      with adverse pregnancy outcome. In the rat, vitamin A deficiency reduces both
      foetal number and neonatal survival. The role of the placenta is uncertain. The
      effects of maternal vitamin A deficiency on placental cytokines and apoptosis
      have been investigated. METHOD OF STUDY: Pregnant rats were fed either control or
      vitamin A free (VAF) diets (n = 4/group) from 8 weeks prior to and throughout
      pregnancy. Day 20 placentas from viable foetuses were examined for
      immunoexpression of (a) cytokines: tumour necrosis factor-alpha (TNF-alpha),
      TNFR1 receptor (p55), leptin and leptin receptor, (b) apoptosis: TdT-mediated
      dUTP nick end-labelling (TUNEL) positive cells, bax and bcl-2. RESULTS: Placentas
      from VAF rats, but not controls, exhibited an infiltrate of neutrophils positive
      for TNF-alpha and leptin. The number of TNFR1 (p55) and TUNEL positive
      trophoblast cells was increased specifically in areas of neutrophil infiltration.
      Trophoblast giant cells in VAF placentas exhibited reduced bax but no change in
      bcl-2. CONCLUSIONS: Maternal vitamin A deficiency is associated with abnormal
      placental apoptosis induced by neutrophil derived TNF-alpha acting through the
      TNFR1 (p55) and/or a change in the bcl-2/bax ratio in the trophoblast giant
      cells. These changes may underlie the effects of vitamin A deficiency on foetal
      development.

PMID- 12069202
TI  - Modulation of T-cell CD3-zeta chain expression in early pregnancy.
AB  - PROBLEM: To assess the modulation of T-cell CD3-zeta chain expression by a factor
      in the sera of women, prior to egg retrieval and 14 days after an in vitro
      fertilization (IVF) and to delineate the mechanism of this modulation. METHOD OF
      STUDY: In this prospective study, blood samples were obtained from 17 patients
      during an IVF cycle, prior to human chorionic gonadotropin (hCG), and 14 days
      after embryo return. Serum was incubated with cultured T-lymphocytes (Jurkat
      cells) for 96 hr and expression of CD3-zeta chain was evaluated. RESULTS: Eight
      patients had a positive serum hCG titer 14 days after retrieval, while nine
      patients had a negative hCG titer. Serum from pregnant patients significantly
      suppressed CD3-zeta chain expression as compared with their sample prior to
      retrieval (85.6 +/- 6.2%), while subjects not becoming pregnant failed to
      suppress zeta expression (99.1 +/- 0.9%, P < 0.0001). CONCLUSION: A factor
      capable of suppressing TcR/CD3-zeta expression can be detected in the sera of
      pregnant women 14 days after embryo retrieval. Loss of zeta chain was associated
      with the induction of apoptosis.

PMID- 12069203
TI  - Restricted entry of IgG into male and female rabbit reproductive ducts following
      immunization with recombinant rabbit PH-20.
AB  - PROBLEM: Successful immunocontraception using sperm antigens is dependent on
      achieving sufficient sperm-specific antibody in the reproductive ducts to prevent
      fertilization. The blood: luminal barrier of the male and female reproductive
      ducts must be overcome for this to occur. We have, therefore, investigated the
      relative titers of antigen-specific immunoglobulin G (IgG) in luminal fluids
      collected from male and female rabbit reproductive ducts following immunization
      with recombinant rabbit PH-20 (rPH-20). METHOD OF STUDY: Male and female rabbits
      were immunized subcutaneously with rPH-20 in Freund's adjuvant. Reproductive
      tract fluids and plasma were collected and assayed for specific IgG by enzyme
      linked immunoabsorbent assay (ELISA). Plasma anti-rPH-20 antibodies were tested
      for their ability to inhibit in vitro fertilization. RESULTS: Plasma rPH-20
      specific IgG titers of > 21 x 106 were induced in bucks. Antibody levels in the
      rete testis and cauda epididymidis fluids were only 0.026 and 0.168% of plasma
      levels, respectively. Plasma IgG titers were > 30 x 10(6) in does, but antibody
      levels in free flow vaginal fluid, free flow uterine fluid and free flow oviduct
      fluid were only 0.016, 0.078 and 0.072% of plasma levels, respectively. Induction
      of ovulation by administration of human chorionic gonadotrophin (hCG)
      significantly increased rPH-20-specific IgG only in free flow vaginal fluids.
      Plasma antibody from immunized rabbits inhibited in vitro fertilization but
      conception rates following mating of rPH-20 immunized male to untreated female
      rabbits were not affected. CONCLUSIONS: The IgG antibody entry into the
      reproductive ducts of both male and female rabbits is restricted to less than
      0.2% of levels induced in plasma following subcutaneous immunization. This
      finding raises doubts about the suitability of rPH-20 to induce
      immunocontraception in rabbits using strategies optimized for induction of a
      serum antibody response. Whether mucosal immunization strategies can achieve this
      remains to be tested.

PMID- 12069204
TI  - Transfer of prostasomal CD59 to CD59-deficient red blood cells results in
      protection against complement-mediated hemolysis.
AB  - PROBLEM: Prostasomes isolated from human seminal plasma have complement
      regulatory properties because of their content of CD59, a
      glycosylphosphatidylinositol (GPI)-anchored protein. We investigated a functional
      role of prostasomes by the possibility of transferring CD59 from prostasomes to
      rabbit erythrocytes (RE) and human erythrocytes obtained from patients with
      paroxysmal nocturnal hemoglobinuria (PNH), both types of cells lacking CD59.
      METHOD OF STUDY: We used the assay of hemolytic activity of the alternative
      pathway of the complement system to compare the liability of the erythrocytes to
      hemolysis by the complement system with and without pre-incubation with
      prostasomes. CD59 gained by the RE and PNH erythrocytes was established by flow
      cytometry. The effect of phosphatidylinositol phospholipase C (PIPLC) on the GPI
      anchor of prostasomal CD59 and the effect of heat treatment on the prostasomes
      were also studied. Anti-CD59 antibodies were used to block the protective effect
      of prostasomes on erythrocytes. RESULTS: Both RE and PNH erythrocytes showed
      diminished complement-mediated hemolysis after incubation with prostasomes. This
      was because of the transfer of CD59 from prostasomes to the red blood cells
      during pre-incubation as evidenced by the hemolytic assay and flow-cytometry. The
      efficacy of the prostasomes was affected by heat treatment and was totally lost
      at 100 degrees C. Phosphatidylinositol phospholipase C broke the GPI anchor and
      released CD59 from prostasomes and the RE surface (after pre-incubation with
      prostasomes) but not from the human PNH erythrocytes. CONCLUSIONS: A transfer
      mechanism of CD59 takes place during pre-incubation from prostasomes to
      erythrocytes lacking CD59 which supports the idea that transfer of prostasomal
      CD59 can protect cells from lysis elicited by C5b-9. This might be a mechanism by
      which autologous and allogeneic cells are protected against complement attack in
      the genital tracts.

PMID- 12069205
TI  - Alert! New revisions to HIPPA privacy rules.

PMID- 12069206
TI  - NMA develops strategic plan against health disparities. National Medical
      Association.

PMID- 12069207
TI  - Managing HIPAA business associate compliance efforts. Health Insurance
      Portability and Accountability Act.

PMID- 12069208
TI  - Correctional health care: implications for public health policy.
AB  - "Correctional Health Care: Implications for Public Health Policy" is the first in
      a series of articles that examines the special health care needs of persons who
      are incarcerated in America's correctional facilities. The intent of the series
      is to gain a better understanding about the unmet health needs of incarcerated
      persons, the importance of addressing the health service delivery system in
      correctional facilities, and the implications that may arise from neglecting to
      address these health issues on health outcomes for individual detainees and
      society at-large when detainees transition back into the community. This article
      provides a descriptive overview of the corrections population, their
      sociodemographics, health care needs, and health concerns that are in need of
      improvement. This article also offers recommendations for public policy
      consideration to improve the overall health of inmates and society at large.

PMID- 12069209
TI  - Misperceptions about HIV transmission among heterosexual African-American and
      Latino men and women.
AB  - This research was conducted to identify myths and misperceptions about HIV/AIDS
      and barriers to risk reduction among heterosexual African-American and Latino
      American men and women in Houston, Texas. Sixty four Latino-American and 69
      African-American men and women, aged 13 to 59 years, participated in 10 and 11
      focus groups, respectively. Each group was audiotaped, transcribed, and analyzed
      using theme and domain analysis. The data confirmed the existence of myths and
      misperceptions among both groups about HIV/AIDS, specifically that HIV is an
      agent of genocide, suspicion of government information, belief that one can
      identify risky partners by odor and appearance, that partners' reported histories
      are accurate, significant misperceptions as to the meaning of "safe sex"
      (particularly in women), and belief that specific classes of people (not
      including oneself) are at risk for HIV. These data strongly suggest that
      concentration on narrow targeting of misinformation common in particular minority
      populations is important in the development of HIV/AIDS prevention programs.

PMID- 12069210
TI  - Symptom clusters in the diagnosis of affective disorder, schizoaffective
      disorder, and schizophrenia in African Americans.
AB  - The purpose of this study is to examine intercategory agreement among the symptom
      clusters associated with diagnoses of affective disorder, schizoaffective
      disorder, and schizophrenia in 156 African-American patients. It is hypothesized
      that there will be greater agreement between diagnosed schizoaffective disorder
      and schizophrenia than either of these two disorders and affective disorder in a
      sample of African-American patients. Patients' diagnoses and symptoms of
      psychopathology, recorded by psychiatrists during hospital admission, were
      abstracted during chart reviews. The symptom clusters for diagnoses of
      schizoaffective disorders overlapped 41% with those of affective disorders and
      71% with those of schizophrenia. The results support the assumption that
      schizoaffective disorder falls within the spectrum of schizophrenia disorders.
      Implications for studies involving the differential diagnosis of affective
      disorder and schizophrenia in African Americans are discussed.

PMID- 12069211
TI  - Arterialization of peripheral venous blood in sickle cell disease.
AB  - Arterialization of the venous blood is thought to be indicative of cutaneous
      shunting, and occurs in patients with sickle cell disease (SCD) during vaso
      occlusive crisis (VOC). We performed the present study to quantify the amount of
      shunting that occurs in sickle cell patients presenting at the Howard University
      Sickle Cell Center, Washington, D.C., as outpatients and for hospitalizations
      associated with sickle cell crisis. Peripheral venous blood was drawn
      anaerobically into heparinized syringes from 9 normal control subjects (NC), 24
      outpatients (steady-state group), and 14 inpatients during crisis (VOC group).
      Spectrophotometric measurements were made for the following species of hemoglobin
      (Hb): oxy-Hb (O2Hb), reduced Hb (RHb), carboxy-Hb (COHb), and met-Hb (MHb). In
      addition, fetal hemoglobin (HbF) was measured by high-pressure liquid
      chromatography (HPLC). The O2Hb saturations of the steady state group were not
      significantly different than those of the NC group (55 +/- 4% vs. 40 +/- 6%).
      However, the O2Hb saturations of the VOC group were 73 +/- 3%, and this value was
      found to be significantly greater than those of both the steady-state and the NC
      groups (p < 0.05). Reduced hemoglobin saturations were inversely related to the
      O2Hb values, as expected. Compared to the NC group, the steady-state, and VOC
      groups had greater dyshemoglobin (COHb and MHb) levels (p < 0.05). These findings
      suggest that the percentages of venous O2Hb and dyshemoglobins may be increased
      in sickle cell disease even in the absence of VOC. Therefore, the venous O2Hb
      saturation may be a useful biochemical marker for the arteriovenous shunting and
      hemodynamic adaptations associated with sickle cell disease.

PMID- 12069212
TI  - Comprehensibility of measures of health-related quality of life in minority and
      low-income patients.
AB  - Although the use of self-administered measures of health-related quality of life
      has increased, their performance in minorities and persons of low socioeconomic
      status is largely unknown. This cross-sectional study assessed participation
      rates, comprehensibility, and overall scores for three generic measures of health
      status--the Short Form-12, EuroQol EQ-5D, and Health Utilities Index Mark 2/3.
      Participants at an inner-city community health center completed demographic
      questions, the measures, and questions regarding the comprehensibility and
      relevance of the measures. Three hundred ninety-three persons were approached,
      and 301 (77%) agreed to participate: 51% were Latino and 32% were African
      American. Sixty-eight percent of participants earned $15,000 or less, and 46% had
      a high school education or lower. Seventeen percent of participants required
      assistance on one or more item, but most sought clarification for only one item.
      Participants' responses on similar questions from two different measures were
      consistent (kappa = .65), and overall scores for the three measures were
      moderately or strongly correlated, ranging from r = .41 to r = .69. Mean scores
      were lower than published population norms. Participants were able to complete
      the self-administered measures and appeared to comprehend the measures. Responses
      from the measures yielded apparently valid results, and scores are likely to be
      lower than higher socioeconomic status populations. Mean scores were comparable
      to scores of persons with chronic diseases. The results suggest that these
      measures may be successfully used in characterizing the health of minority and
      low-income populations.

PMID- 12069214
TI  - The search for value in health care: a review of the National Committee for
      Quality Assurance efforts.
AB  - Large employers formed the National Committee for Quality Assurance (NCQA) to
      ensure value to healthcare purchasers. Value in healthcare is a function of
      quality divided by costs. Through NCQA's role as an accrediting agency for
      healthcare organizations and the development of performance measures, Health Plan
      Employer Data and Information Set (HEDIS), gains toward defining the value of
      health services have materialized. An analysis of the impact of HEDIS data
      collection on physician practices and the influence of HEDIS data on employer,
      employee, and governmental health plan selections is examined. This study
      consisted of a general review, from 1993 to 2001, of HealthStar databases, PubMed
      databases, and the NCQA website. NCQA accreditation is accepted as an important
      industry milestone for health plans, credentials verification organizations, and
      physician organizations. The data for HEDIS is collected from health plan
      administrative data repositories, whereas health plan members' clinical data may
      be collected by chart abstraction in physician offices. Data collection in
      physician offices consumes administrative resources from physician practices and
      health plans. As commercial and governmental insurers move toward greater
      adoption of HEDIS measures, complex implications are created for physician
      practices and vulnerable populations. There are lingering questions regarding the
      improvements in quality of care for medically underserved populations and
      physician practice costs attributable to HEDIS.

PMID- 12069213
TI  - Contribution of substance abuse and HIV infection to psychiatric distress in an
      inner-city African-American population.
AB  - We used Symptom Checklist 90-Revised (SCL90-R) to investigate psychiatric symptom
      severity in African-American drug-abusing individuals. Three hundred and
      seventeen African-American volunteers (52 control subjects; 265 drug users) were
      recruited, 19.2% of whom were HIV-positive. The impact of drug of choice or HIV
      status on mental distress was assessed. Symptomatic HIV-positive participants
      were excluded. The intake SCL90-R, Addiction Severity Index, and demographic data
      were subjected to regression analyses. Drug-abusing African Americans reported
      increased global distress, a finding that remained robust after we adjusted for
      HIV status, gender, age, and education. Drug of choice had no influence on the
      severity of global mental distress in our sample. Asymptomatic HIV-positive
      African Americans who abused drugs reported more distress than the HIV-negative
      drug users. Levels of global distress were similar in the HIV-negative and the
      HIV-positive controls. Subscales of the SCL90-R showed more symptom severity
      among drug-using, compared with nonusing, African Americans. Except for paranoia,
      anxiety, and obsessive-compulsive subscales, other symptom dimensions were
      significantly elevated in HIV-positive, compared with HIV-negative, drug abusers.
      When taken together, these findings suggest that drug abuse can exacerbate the
      severity of mental distress in HIV-positive patients. Treatment of these patients
      may be more successful if both sets of needs are addressed with matched
      interventions.

PMID- 12069215
TI  - Quality in health care--is something better than nothing?

PMID- 12069217
TI  - Parental monitoring intervention: practice makes perfect.
AB  - Data from a randomized, controlled longitudinal study of African-American parent
      adolescent dyads were analyzed to assess the impact of a parental monitoring
      intervention on (a) the similarity of parent and adolescent reporting of
      adolescent involvement in risk and protective activities, and (b) the reported
      rates of risk involvement by youth. Self-reported and parental perception of
      youth risk and protective activities were collected at baseline and 12 months
      postintervention. There was no significant difference between self-report and
      parent perception of youth activities among intervention dyads at follow-up. By
      contrast, parents in the control dyads significantly underestimated youth
      protective and risk activities. There was no evidence of a direct intervention
      effect on self-reported risk behaviors. These data confirm earlier findings that
      a culturally-tailored parental monitoring intervention can increase agreement of
      youth risk involvement among youth and their parents and provide evidence that
      this effect endures over time. The data argue for the need to consider
      intervention strategies that address both parents and youth.

PMID- 12069216
TI  - Factors associated with patient-recalled smoking cessation advice in a low-income
      clinic.
AB  - It is recommended that providers advise cessation to their patients who smoke.
      However, patients' reports of cessation advice indicate disparities based on
      patients' race, gender, age, and smoking level. Providers' reports do not
      corroborate these disparities. We investigated whether smokers who receive their
      care in a community health center recalled their providers advising them to quit
      smoking when their providers documented such advice. We examined 219 patient
      provider dyads to assess factors associated with lack of agreement between
      providers' documentation and patient recall. Patients were asked to recall any
      provider advice to quit smoking in the post 2 years. After every visit, providers
      completed a form to record the content of the visit. Most of the patients were
      African American, married, and uninsured. Sixty-eight percent of the dyads agreed
      in their documentation/recall. Patient race was the only factor associated with
      lack of agreement; African-American patients were more likely than white patients
      to provide discrepant reports. Although this study can not disentangle the racial
      difference in patient-provider recall/documentation, results may indicate an
      important area in which health disparities exist. Future studies should address
      the dynamics of patient-provider communication about smoking cessation,
      especially in populations that include ethnically diverse patients.

PMID- 12069218
TI  - Religion/spirituality in African-American culture: an essential aspect of
      psychiatric care.
AB  - There is an astonishing diversity of religious beliefs and practices in the
      history of African Americans that influences the presentation, diagnosis, and
      management of both physical and mental disorders. The majority of African
      Americans, however, are evangelical Christians with religious experiences
      originating in the regions of ancient Africa (Cush, Punt, and to a great extent,
      Egypt), as well as black adaptation of Hebraic, Jewish, Christian, and Islamic
      beliefs and rituals. Consequently, more than 60 of the nation's 125 medical
      schools offer classes in spirituality and health. Although there is a lack of
      empirical evidence that religion improves health outcomes, physicians should
      understand patients as a biopsychosocial-spiritual whole. Asking about
      religion/spirituality during a health assessment can help the physician determine
      whether religious/spiritual factors will influence the patient's medical
      decisions and compliance. Two psychiatric case histories of African Americans are
      presented in which religion/spirituality significantly influenced treatment
      decisions and results. Neither of these patients suffered major debilitating
      medical comorbidity.

PMID- 12069219
TI  - NDA II: summary documentation of a health professional organization. National
      Dental Association.

PMID- 12069220
TI  - Thyrotoxic hypokalemic periodic paralysis in a Hispanic male.
AB  - We report a case of a Hispanic male presenting with acute onset of bilateral
      lower extremity weakness, without any antecedent viral or bacterial illness,
      dietary changes, infiltrative orbitopathy, diffuse goiter, infiltrative
      dermopathy, and family history of periodic paralysis, who was later found to have
      Graves' disease. This demonstrates a rare case of periodic paralysis as the
      initial presentation of hyperthyroidism. Thyrotoxic hypokalemic periodic
      paralysis is common in Asian and Hispanic individuals and uncommon in whites and
      African Americans.

PMID- 12069221
TI  - More on after-hours telephone calls by parents.

PMID- 12069222
TI  - An integrated microfabricated cell sorter.
AB  - We have developed an integrated microfabricated cell sorter using multilayer soft
      lithography. This integrated cell sorter is incorporated with various
      microfluidic functionalities, including peristaltic pumps, dampers, switch
      valves, and input and output wells, to perform cell sorting in a coordinated and
      automated fashion. The active volume of an actuated valve on this integrated cell
      sorter can be as small as 1 pL, and the volume of optical interrogation is
      approximately 100 fL. Different algorithms of cell manipulation, including cell
      trapping, were implemented in these devices. We have also demonstrated sorting
      and recovery of Escherichia coli cells on the chip.

PMID- 12069223
TI  - Major factors affecting the isotopic measurement of chlorine based on the Cs2Cl+
      ion by thermal ionization mass spectrometry.
AB  - The factors that affect isotopic measurement of chlorine based on Cs2Cl+ ion by
      thermal ionization mass spectrometry were studied. Graphite is essential for the
      emission of Cs2Cl+ ion from CsCl. No Cs2Cl+ ions are detected in the absence of
      graphite on the filament. The emission of Cs2Cl+ ion and the measured 37Cl/35Cl
      ratio were affected by different varieties of graphite, the pH value of the
      sample solution, and impurities in the solution. High-precision isotopic
      measurement of chlorine based on Cs2Cl+ ion is achieved only by using graphite
      with a perfect crystal structure. The measured 37Cl/35Cl ratios were much higher,
      and even the emission of Cs2Cl+ ion becomes impossible when pH values of the
      sample solution were higher than 6, corresponding to the presence of excess Cs.
      The measured 37Cl/35Cl ratios were higher when SO4(2-) and NO3- anions were
      present. The results show that the measured 37Cl/35Cl ratios are weakly related
      to the amount of chlorine on filament in a range from 1 to 500 microg.

PMID- 12069224
TI  - Detecting large biomolecules from high-salt solutions by fused-droplet
      electrospray ionization mass spectrometry.
AB  - A novel fused-droplet electrospray ionization (FD-ESI) source was developed to
      generate peptide and protein ions. The sample solution was first ultrasonically
      nebulized to form fine aerosols. The aerosols were then purged into a glass
      reaction chamber via nitrogen. Charged methanol droplets were continuously
      generated through electrospraying the acidic methanol solution from a capillary,
      which was located at the center of the reaction chamber. As the sample aerosols
      entered the reaction chamber, they fused with the charged methanol droplets from
      which electrospray proceeded continuously. The mass spectra of peptide and
      protein that FD-ESI-MS produced were practically identical to those that
      conventional ESI-MS produced. However, FD-ESI-MS resulted in an extremely high
      salt tolerance. Cytochrome c ions were detected in the solutions that contained
      10% (w/w; 1.709 M) NaCl or 2.5% (425 mM) NaH2PO4. As with those obtained from the
      solution that lacked NaCl and NaH2PO4, the width of cytochrome c ion peaks
      remained nearly unchanged.

PMID- 12069225
TI  - Characterization of silica-based monoliths with bimodal pore size distribution.
AB  - Band dispersion was studied and the retention thermodynamics addressed for
      insulin and angiotensin II on C18 silica monoliths with a bimodal pore size
      distribution, covering linear mobile-phase velocities up to 1 cm/s and different
      temperatures. These data suggest that the influence of average column pressure on
      retention (between 0 and 10 MPa) is not negligible. Plate height curves were
      interpreted with the van Deemter equation by assuming an independent contribution
      from mechanical and non-mechanical dispersion mechanisms. This analysis revealed
      diffusion-limited mass transfer in the mesoporous silica skeleton which, in turn,
      allowed us to calculate an equivalent dispersion particle diameter (d(disp) = 3
      microm) using the C-term parameter of the van Deemter equation. The resulting
      superposition of reduced plate height curves for monolithic and particulate beds
      confirmed that this view presents an adequate analogy. The macroporous
      interskeleton network responsible for the hydraulic permeability of a monolith
      was translated to the interparticle pore space of particulate beds, and an
      equivalent permeability particle diameter (d(perm) = 15 microm) was obtained by
      scaling based on the Kozeny-Carman equation.

PMID- 12069226
TI  - Correction for particle-wall interactions in the separation of colloids by flow
      field-flow fractionation.
AB  - In the characterization of materials by field-flow fractionation (FFF), the
      experienced analyst understands the importance of incorporating additives in the
      carrier liquid that minimize or eliminate interactions between the analyte and
      accumulation wall, particularly in aqueous systems. However, as FFF is applied to
      more difficult samples, such as those with high surface energies, it is
      increasingly difficult to find additives that completely eliminate particle-wall
      interactions. Furthermore, the analyst may wish to use specific conditions that
      preserve the high surface energy of particles, to study their interaction with
      other materials through their behavior in the FFF channel. With this in mind,
      Williams and co-workers developed a model that quantifies the effect of particle
      wall interactions in FFF using an empirically determined interaction parameter.
      In this work, the model is evaluated for the application of flow FFF in carrier
      liquids of low ionic strength, where particle-wall interactions are magnified.
      The retention of particles ranging in size from 64 to 1000 nm is measured using a
      wide range of field strengths and retention levels. The model is found to be
      generally valid over the entire range, except for minor discrepancies at lower
      levels of retention. Although retention levels are dramatically affected by
      particle-wall interactions, the point of steric inversion (500 nm), where the
      size-based elution order reverses, is not affected. When particle-wall
      interactions are not accounted for, they lead to a bias in particle sizes
      calculated from standard retention theory of up to 70%. The model can also be
      used to refine the measurement of channel thickness, which is important for the
      accurate conversion of retention parameters to particle sizes. In this work, for
      example, errors in channel thickness led to systematic errors on the order of 10%
      in particle diameter.

PMID- 12069227
TI  - Liquid-phase microextraction combined with hollow fiber as a sample preparation
      technique prior to gas chromatography/mass spectrometry.
AB  - Two modes of liquid-phase microextraction (LPME) combined with hollow fiber (HF)
      were developed for gas chromatography/mass spectrometry (GC/MS). Both
      methodologies, that is, static LPME with HF and dynamic LPME with HF, involved
      the use of a small volume of organic solvent impregnated in the hollow fiber,
      which was held by the needle of a conventional GC syringe. In static LPME/HF, the
      hollow fiber impregnated with solvent was immersed in the aqueous sample, and the
      extraction processed under stirring; in dynamic LPME/HF, the solvent was
      repeatedly withdrawn into and discharged from the hollow fiber by a syringe pump.
      This is believed to be the first reported instance of a semiautomated liquid
      microextraction procedure. The performance of the two techniques was demonstrated
      in the analysis of two PAH compounds in an aqueous sample. Static LPME/HF
      provided approximately 35-fold enrichment in 10 min and good reproducibility
      (approximately 4%). Dynamic LPME/HF could provide higher enrichment
      (approximately 75-fold) in 10 min and even better reproducibility (approximately
      3%). Both methods allow the direct transfer of extracted analytes to a GC/MS
      system for analysis.

PMID- 12069228
TI  - Fast identification of Echinacea purpurea dried roots using near-infrared
      spectroscopy.
AB  - Near-infrared (NIR) reflectance spectroscopy was used to develop a fast
      identification method for Echinacea purpurea dried milled roots. Method
      development was carried out using a PLS (partial least-squares) algorithm and
      pretreatment options. The aim of this qualitative analysis was to confirm the
      identity of E. purpurea and to detect the presence of fraud, i.e., samples
      adulterated or substituted by Echinacea angustifolia, Echinacea pallida, or
      Parthenium integrifolium. Specificity was demonstrated by testing a validation
      set against the method. A total of 10% of the E. purpurea batches (true samples)
      and 0% of the false samples from that validation set were misidentified by the
      method. The misidentification was due to the difference in particle size
      distribution of one E. purpurea batch compared to that of the other samples.
      Adulterated E. purpurea samples can be detected at a minimum of 10% of
      adulteration. This study demonstrates that NIR spectroscopy is a good tool for
      the fast identification of E. purpurea roots if the samples are milled using the
      same procedure as for the calibration samples. The method is robust with respect
      to the origin of the samples and can be used routinely by the pharmaceutical
      industry or herbal suppliers to avoid mislabeling errors or adulteration.

PMID- 12069229
TI  - A homogeneous noncompetitive immunoassay for the detection of small haptens.
AB  - We describe a noncompetitive homogeneous immunoassay for small haptens based on
      the antigen-dependent reassociation of antibody variable domains and beta
      galactosidase (beta-gal) complementation (open sandwich enzymatic complementation
      immunoassay). As a model system, the reassociation of two fusion proteins, an
      anti 4-hydroxy-3-nitrophenylacetyl (NP) antibody heavy-chain variable-region
      fragment fused to an N-terminal deletion mutant of beta-gal (V(H)delta alpha) and
      the light-chain variable-region fragment fused to a C-terminal deletion mutant of
      beta-gal (V(L)delta omega), was monitored by the enzymatic complementation
      between the two. Upon simple mixing of the reagents with the sample, an antigen
      (NP)-dependent increase in enzymatic activity was observed. When 5-iodo-NP was
      measured, a 10 times higher sensitivity was observed, probably due to its higher
      affinity. Compared with our corresponding heterogeneous open sandwich enzyme
      linked immunosorbent assay, approximately 1000-fold improvement in the
      sensitivity was attained, probably due to lower background V(H)-V(L) association.
      In addition, the assay required less time, handling, sample volume, and assay
      reagents.

PMID- 12069230
TI  - Application of isotopically labeled methylmercury for isotope dilution analysis
      of biological samples using gas chromatography/ICPMS.
AB  - An isotope dilution (ID) procedure for the determination of methylmercury (MMHg)
      in biological samples using an inductively coupled plasma mass spectrometer as
      detector after the capillary gas chromatographic separation (CGC/ICPMS) has been
      developed. For the first time, open-focused-microwave pretreatment has been used
      in conjunction with ID. Optimum conditions for the measurement of isotope ratios
      on the fast transient chromatographic peaks have been established. Mass bias was
      found to be about 1.5%/mass unit and was corrected by using the simultaneously
      measured thallium signals at 203Tl and 205Tl. After mass-bias correction,
      deviation of the theoretical mercury ratio values was found to be as low as 0.2%.
      Isotope ratio precisions based on the peak areas measurements were 0.3% RSD for
      20 pg injected (as Hg absolute). The absolute detection limits were in the range
      of 20-30 fg for 202Hg and 201Hg. Methylmercury enriched in 201Hg has been
      synthesized by direct reaction with methylcobalamine. The concentration of the
      MMHg spike has been measured by reverse isotope dilution with a natural MMHg
      standard. The capabilities of CGC/ICPMS to measure isotope ratios were used to
      optimize sample derivatization by aqueous ethylation with NaBEt4 with respect to
      MMHg degradation pathways and quantitative recovery. The accuracy of the method
      developed has been validated with biological certified reference materials (CRM
      463, DORM-1).

PMID- 12069232
TI  - Liquid-liquid extraction of alkali metal ions with photochromic crowned
      spirobenzopyrans.
AB  - On the liquid-liquid extraction using 1,2-dichloroethane as an organic solvent,
      the crowned spirobenzopyrans exhibited textractability in the following order:
      Li+ >> Na+ > K+ > or = tetramethylammonium ion (TMA+), Li+ > Na+ >> K+ > TMA+,
      and Na+ > K+ >> Li+ > TMA+ for spirobenzopyran derivatives bearing monoaza-12
      crown-4, 1; monoaza-15-crown-5, 2; and monoaza-18-crown-6, 3; respectively, under
      dark conditions. The ion selectivity of 1 depends on the metal-ion complexing
      ability of monoaza-12-crown-4. Even 2, which carries a 15-crown-5 moiety, showed
      Li+ selectivity because of the much stronger interaction of Li+ with the
      phenolate ion of the merocyanine form of 2 than that of Na+. The Na+ selectivity
      of 3 is also attributed to the ionic interaction with the phenolate ion of the
      merocyanine form, since the ionic interaction prefers Na+ to K+ regardless of the
      higher affinity of the 18-crown-6 ring itself to the latter ion. The Li+
      extraction into the organic phase with 1 was enhanced by UV irradiation (300-400
      nm), while some depression in the extraction was found by visible irradiation
      (>500 nm). The effect of visible irradiation on the Li+ complexing ability of 1
      was also examined with electrospray ionization mass spectrometry.

PMID- 12069231
TI  - Use of L-lysine fluorescence derivatives as tracers to enhance the performance of
      polarization fluoroimmunoassays. A study using two herbicides as model antigens.
AB  - Fluorescence polarization immunoassay (FPIA) is a convenient homogeneous assay,
      the use of which is restricted in environmental analysis by low sensitivity and
      matrix effects. We selected the herbicides 2,4D and 2,4,5T to synthesize new L
      lysine-based fluorescent tracers using solid-phase chemistry. In addition, three
      different immunogens of 2,4,5T were prepared for immunization and antibody
      production. The new tracers and antibodies were adapted to FPIA. Tracers with the
      hapten attached to the alpha-aminogroup of L-lysine and fluorescein to the e
      amino group exhibited at least a 5-fold increased sensitivity when compared to
      the previously reported ethylenediamine-based tracer (2,4D-EDA-F). The isomeric
      structure (hapten attached to the e-amino and fluorescein to the alpha-amino
      group) appeared 7.6 times less sensitive, and all other alternative structures
      exhibited even lower sensitivities. This observation was confirmed against the
      monoclonal anti-2,4D antibody E2/G2 and polyclonal anti-2,4,5T antibodies. The
      affinity constant of 2,4D-EDA-F with E2/G2 was 8.1 times higher when compared
      with the new tracer, suggesting the more specific nature of the L-lysine-based
      tracer, the use of which leads to a more sensitive assay. This type of tracer
      could improve performance and lower substantially the detection limits of FPIAs.

PMID- 12069233
TI  - Mass spectrometry-based proteolytic mapping for rapid virus identification.
AB  - A novel method is proposed for rapid identification of viruses and other
      organisms that show a low number of biomarkers, based on the construction of
      databases of organism-specific tryptic peptide masses. The peptide products of
      any protease that cuts at specific residues can be accommodated. Experimentally,
      a sample of intact virus, e.g., one collected from the atmosphere, is digested
      with a selective protease for a short time, and the digestion products are
      analyzed by MALDI-TOF mass spectrometry without fractionation or purification. In
      the present proof of concept, the Sindbis virus AR 339 was identified by using
      the masses of observed tryptic peptide products to query a database composed of
      tryptic peptide masses generated in silico for six viruses whose genomes have
      been sequenced. Two algorithms were tested for identification--a direct score
      ranking algorithm and an algorithm that evaluates the probability of random
      matching. The Sindbis virus was unambiguously identified by either approach. The
      influence of factors such as experimental mass accuracy, number of missed
      cleavages, and database size on the identification algorithms has also been
      evaluated, with the objective of extending the approach to other microorganisms.

PMID- 12069234
TI  - High-acidity determination in salt-containing acids by optical sensors. The scope
      of a dual-transducer approach and the Hammett acidity function.
AB  - A dual-transducer approach based on sol-gel optical sensors was recently reported
      to measure acid and salt concentrations, C(acid) and C(salt), in concentrated
      aqueous LiCl-HCl, CaCl2-HCl, and AlCl3-HCl solutions (C(acid) at 5-6 M; C(salt) <
      or = 2 M). The scope of this new approach has been studied in salt-containing HCl
      solutions with C(acid) at 2-9 M, and factors that influence sensor responses and
      accuracy have been investigated. A linear relationship between
      (deltaA/deltaC(salt))C(acid) and (dA/dC(acid))C(salt)=0, which is the basis of
      this dual-transducer approach, was found to lead to an empirical linear
      relationship between (deltaH0)C(acid) and (deltaC(salt))C(acid) (H0: Hammett
      acidity function of the indicator encapsulated in the sensor).

PMID- 12069236
TI  - Characterization of a cross-reactive electronic nose with vapoluminescent array
      elements.
AB  - A three-channel cross-reactive sensor array based on vapoluminescent platinum(II)
      double salt materials has been characterized. Two arrays were studied, one
      consisting of [Pt(CN-cyclododecyl)4][Pt(CN)4] (1), [(phen)Pt(CN
      cyclohexyl)2][Pt(CN)4] (2), and [Pt(CN-n-tetradecyl)4][Pt-(CN)4] (3) materials,
      where phen = 1,10-phenanthroline, and a second array that has compound 3 replaced
      by the mixed double salt material [(phen)Pt(CN-cyclododecyl)Cl)]2[(phen)Pt(CN
      cyclododecyl)2]2[Pt(CN)4]3 (4). Compounds 2, 3 and 4 are characterized here for
      the first time. Inclusion of solvent vapors into these materials often leads to
      dramatic shifts in their solid-state absorption and luminescence spectra. In
      these studies the arrays were exposed to a set of 10 test solvent vapors to
      determine the ability of each cross-reactive array to give reproducible
      vapoluminescent spectra characteristic of each solvent vapor. It was discovered
      that temperature programming between solvent vapor exposures greatly improved the
      reproducibility of the luminescence spectra obtained. A statistical analysis of
      three-dimensional resolution factors between pairs of solvent clusters in
      principal component space supported this assertion. The success of the
      temperature programming protocol was limited by the thermal stability and the
      sensitivity to low background water vapor levels of some platinum(II) double salt
      materials. The ability of the cross-reactive sensor array to differentiate
      between two different solvent vapors over a large concentration range was also
      investigated. Acetone and methanol were found to occupy two distinct regions of
      the three-dimensional principal component space. Detection limits for acetone and
      methanol were estimated from the principal component analysis as 75 and 6 g/m3,
      respectively.

PMID- 12069235
TI  - Elemental mapping in natural rubber latex films by electron energy loss
      spectroscopy associated with transmission electron microscopy.
AB  - Element distribution maps from Hevea brasiliensis natural rubber latex thin films
      were obtained, by electron energy-loss spectroscopic imaging in a low-energy (80
      kV) transmission electron microscope. C, N, O, P, Na, Ca, Mg, Al, Si, and S maps
      are presented for latex fractionated by centrifugation, either followed by
      dialysis or not. Most elements forming non-carbon compounds are concentrated in
      small, electron-dense spots surrounded by a carbon-rich matrix of polymer, thus
      showing that the rubber is filled with small particles compatible with the
      polyisoprene matrix. Ca distribution is unique, since it closely parallels the C
      distribution, evidencing an important role for -COO(-)-Ca2+-COO- ionic bridges in
      the structure of natural rubber.

PMID- 12069237
TI  - Microfluidic temperature gradient focusing.
AB  - A new technique is described for the concentration and separation of ionic
      species in solution within microchannels or capillaries. Concentration is
      achieved by balancing the electrophoretic velocity of an analyte against the bulk
      flow of solution in the presence of a temperature gradient. With an appropriate
      buffer, the temperature gradient can generate a corresponding gradient in the
      electrophoretic velocity, so that the electrophoretic and bulk velocities sum to
      zero at a unique point, and the analyte will be focused at that point. The
      technique is demonstrated for a variety of analytes, including fluorescent dyes,
      amino acids, DNA, proteins, and particles, and is shown to be capable of greater
      than 10,000-fold concentration of a dilute analyte.

PMID- 12069238
TI  - High-throughput, high-sensitivity genetic mutation detection by tandem single
      strand conformation polymorphism/heteroduplex analysis capillary array
      electrophoresis.
AB  - We present the first optimization of linear polyacrylamide (LPA)-based DNA
      separation matrixes for an automated tandem microchannel single-strand
      conformation polymorphism (SSCP)/heteroduplex analysis (HA) method, implemented
      in capillary arrays dynamically coated with poly(N-hydroxyethylacrylamide)
      (polyDuramide). An optimized protocol for sample preparation allowed both SSCP
      and HA species to be produced in one step in a single tube and distinguished in a
      single electrophoretic analysis. A simple, two-color fluorescent sample labeling
      and detection strategy enabled unambiguous identification of all DNA species in
      the electropherogram, both single- and double-stranded. Using these protocols and
      a panel of 11 p53 mutant DNA samples in comparison with wild-type, we employed
      high-throughput capillary array electrophoresis (CAE) to carry out a systematic
      and simultaneous optimization of LPA weight-average molar mass (Mw) and
      concentration for SSCP/HA peak separation. The combination of the optimized LPA
      matrix (6% LPA, Mw 600 kDa) and a hydrophilic, adsorbed polyDuramide wall coating
      was found to be essential for resolution of CAE-SSCP/HA peaks and yielded
      sensitive mutation detection in all 11 p53 samples initially studied. A larger
      set of 32 mutant DNA specimens was then analyzed using these optimized tandem CAE
      SSCP/HA protocols and materials and yielded 100% sensitivity of mutation
      detection, whereas each individual method yielded lower sensitivity on its own
      (93% for SSCP and 75% for HA). This simple, highly sensitive tandem SSCP/HA
      mutation detection method should be easily translatable to electrophoretic
      analyses on microfluidic devices, due to the ease of the capillary coating
      protocol and the low viscosity of the matrix.

PMID- 12069239
TI  - Use of a small reporter molecule to determine cell-surface proteins by capillary
      electrophoresis and laser-induced fluorescence: use of 5-SAENTA-x8f for
      quantitation of the human equilibrative nucleoside transporter 1 protein.
AB  - The human equilibrative nucleoside transporter 1 protein (hENT1) is a major
      mediator of cellular entry of nucleosides and anticancer nucleoside drugs; its
      assay is important in understanding and diagnosing chemotherapy resistance. Here
      we present a novel assay for quantifying hENT1 using capillary electrophoresis
      with laser-induced fluorescence detection (CE-LIF). A cellular population is
      treated with 5'-S-(2-aminoethyl)-N6-(4-nitrobenzyl)-5'-thioadenosine-x8
      fluorescein (5-SAENTA-x8f), which binds with high affinity and specificity to the
      hENT1 protein. The cells are washed to remove excess reagent, lysed, and
      centrifuged, and the supernatant is analyzed by CE-LIF with the use of an
      internal standard. Accuracy was evaluated by comparing the capillary
      electrophoresis results with those obtained by flow cytometry; the results were
      highly correlated, r = 0.96. The relative standard deviation of the hENT1 assay
      was 10%, determined from nine independent assays of the same cell line, which is
      3 times superior to results obtained in a flow cytometry assay. The detection
      limit for 5-SAENTA-x8f was 4300 molecules injected into the capillary.

PMID- 12069240
TI  - Attenuated partial internal reflection infrared spectroscopy.
AB  - A new method for the spectroscopic study of absorbing films is proposed. In
      contrast to the well-established methods that take advantage of the attenuation
      of total internal reflection (ATR) to obtain spectra, we intentionally arrange
      the optics to permit partial internal reflection from the sampling prism face.
      Attenuated partial internal reflection (APR) spectroscopy is introduced through
      theoretical calculations and experimental demonstrations. The calculated APR
      spectra in the infrared region were generated from the Fresnel and Airy
      equations. Experimentally, APR spectra of water films on a NaCl prism were
      obtained. APR is more sensitive than ATR, and can easily distinguish water films
      at the monolayer level (310 pm). The determination of film thickness from
      interference fringes in APR spectra is also illustrated. It is shown that APR can
      be used for film thickness measurements that can span 6 orders of magnitude. The
      limitations of APR are also discussed.

PMID- 12069241
TI  - Cathodic electrochemical detection of sonochemical radical products.
AB  - This paper reports on an electrochemical technique for the detection of oxidizing
      radical species, produced as the result of cavitation induced by ultrasound. A
      study of two example reactions is reported: the Weissler reaction and the Fricke
      reaction. In both cases, redox-active materials trap oxidative radicals.
      Electrochemical detection within a flow cell system is then used to sense redox
      active products of the reactions between a chosen trapping agent and radicals
      produced within an ultrasonically irradiated aqueous solution. A demonstration of
      the sensitivity of electrochemical detection of radical products is presented. An
      equivalent dose of the ultrasonic reactor is reported.

PMID- 12069242
TI  - Triiodide PVC membrane electrodes based on charge-transfer complexes.
AB  - Three new electrodes were prepared by incorporating two different charge-transfer
      complexes and amino crown ether into plasticized PVC membranes. The electrodes
      showed Nernstian response to triiodide ion over the activity range from 1.0 x 10(
      5) to 1.0 x 10(-1) mol x L(-1) with detection limits at approximately 1.0 x 10(
      6) mol x L(-1). The resulting electrodes have fast response times (20-30 s) and
      good stabilities (4 months) and can be used over a wide pH range of 2.5-9.0. The
      proposed electrodes exhibit anti-Hofmeister behavior with excellent selectivity
      toward triiodide ion against a wide range of common interferences. Comparative
      study suggests that amino (aza) crown ether alone or in the form of a charge
      transfer complex with iodine, as an ionophore in a PVC liquid membrane, is
      sensitive to triiodide ion. The electrodes were used as indicator electrodes in
      potentiometric titration of triiodide ion against thiosulfate ion.

PMID- 12069243
TI  - High-performance nitrate-selective electrodes containing immobilized amino acid
      betaines as sensors.
AB  - Ten nitrate-selective electrodes based upon rubbery membranes containing various
      betaine salts as sensors covalently bound to a cross-linked polystyrene-block
      polybutadiene-block-polystyrene (SBS) polymer have been produced. The membranes
      were robust, highly selective, and effective over a pH range of 2-8. The best
      nitrate-selective electrode fabricated contained 10% m/m dicumyl peroxide, 40% 2
      nitrophenyloctyl ether, 6.5% triallyl leucine betaine chloride and 43.5% SBS. The
      characteristics of this electrode were a linear Nernstian range of 1 x 10(-1) to
      5 x 10(-6) mol dm(-3) NO3-, a limit of detection of 3.4 x 10(-7) mol dm(-3) NO3-,
      and a selectivity coefficient for nitrate against chloride, K(NO3-,Cl-)pot, of
      3.4 x 10(-3). These figures represent a significant improvement on current
      commercial nitrate sensors. Response times were 1 min or less; stability of
      response and electrode lifetime in continuous use was also very satisfactory.

PMID- 12069244
TI  - Tweezer-type neutral carrier-based calcium-selective membrane electrode with
      drastically reduced anionic interference.
AB  - A new calcium-selective ionophore N,N-dioctyl-3alpha,12alpha-bis(N-heptyl-N
      methylcarbamoyl-methoxyacetamidoacetoxy)-5beta-cholan-24-amide (denoted as BACA),
      was synthesized, and its potentiometric performance has been evaluated in
      comparison with that of the best known calcium-selective neutral carriers, ETH
      129 and ETH 1001. The 1H NMR spectra of BACA titrated with Ca(SCN)2 suggest that
      BACA forms a 1:1 complex, tweezing a calcium ion between the two parallel diamide
      groups substituted on a rigid bile acid frame. The calcium-selective membrane
      based on BACA was less selective to calcium (log K(Ca2+ j)POT = -4.2, -4.2, -4.6,
      and -4.8, respectively, for j = Mg2+, Li+, Na+, and K+) than those based on ETH
      129 (log K(Ca2+ j)POT = -4.4, -4.3, -5.4, and -5.4, respectively, in the same
      order) and ETH 1001 (log K(Ca2+ j)POT = -4.4, -4.4, -5.4, and -5.4), implying
      that BACA forms a weaker calcium complex than the other two ETH compounds. In our
      experimental conditions, potentiometrically determined complex formation
      constants of calcium-selective neutral carriers (log beta(Ca2+ L)) were 15.2,
      14.0, and 8.6 for ETH 129, ETH 1001, and BACA, respectively. A slightly reduced
      calcium selectivity of BACA, however, affects the anionic interference-free
      calcium-selective membrane; the BACA-based membrane exhibits a Nernstian response
      up to 10(-1) M Ca2+ in the presence of lipophilic anions (e.g., SCN-, ClO4-,
      salicylate, and I-) and anionic surfactant, whereas the ETH 129- and ETH 1001
      based ones suffer from serious anionic interference showing a curvature or
      leveled off response over about 10(-4) M. It was demonstrated that such a trade
      off does not affect the analytical performance of BACA-based electrode in most
      applications, including clinical analysis.

PMID- 12069245
TI  - Analysis of phosphate position in hexose monosaccharides using ion-molecule
      reactions and SORI-CID on an FT-ICR mass spectrometer.
AB  - Through the use of ion-molecule reactions and SORI-CID, the phosphate position in
      hexose phosphate monosaccharides has been determined in the negative ion mode.
      Trimethyl borate was used as a reagent gas and was found to react readily with
      the phosphorylated hexose monosaccharides. After reaction of the reagent gas with
      the hexose phosphate, ion activation of the precursor by SORI-CID yielded
      different MS/MS spectra. Different diagnostic ions were generated for the two
      isomers, thus enabling differentiation and linkage position determination of the
      phosphate moiety.

PMID- 12069246
TI  - Characterization of a novel light source for simultaneous optical and scanning
      ion conductance microscopy.
AB  - We have developed a novel light source suitable for imaging of biological
      samples. The method is based on the use of a micropipet filled with fluo-3. A
      fluorogenic complex is formed when fluo-3 meets calcium in the bath solution. The
      complex is excited by focusing a laser beam at the pipet tip to produce a
      submicrometer light source. This source is continually renewed at the tip,
      eliminating problems with photobleaching, and can be controlled by varying the
      applied potential. We first characterized the light source using fluorescence
      correlation measurements in order to optimize its properties. We then recorded an
      image of a model sample under buffer with submicrometer resolution using ion
      conductance distance control to demonstrate the feasibility of this approach.

PMID- 12069247
TI  - Immunoassay with a microtiter plate incorporated multichannel electrochemical
      detection system.
AB  - To extend the application of a multichannel electrochemical detector (MED) for
      immunoassay, a MED system consisting of 8 sets of Pt electrodes in an arrangement
      fitted with the dimensions of a row of microtiter wells in a microtiter plate and
      a microcomputer-assisted 16-channel potentiostat was constructed. With this
      developed MED system, electroactive enzymatic products produced in eight
      microtiter wells can be analyzed simultaneously with a developed amperometric
      procedure. To demonstrate the applicability of the MED system for immunoassay, an
      immunosystem containing rabbit-IgG and alkaline phosphatase-conjugated goat anti
      rabbit-IgG was studied. From the dynamic range of 10-1000 ng/mL (0.064-6.4 pM)
      and the detection limit of 1.0 ng/mL (6.4 pM) obtained, the developed MED shows a
      tremendous improvement in sensitivity, detection limit, and efficiency compared
      with that obtained from conventional electrochemical immunoassay.

PMID- 12069250
TI  - Meeting overload. Are too many conferences too much of a good thing?

PMID- 12069249
TI  - Analyzing individual ultrafine air particles.

PMID- 12069251
TI  - Dietary supplement quality control in the making.

PMID- 12069252
TI  - Analytical applications of single-molecule detection.

PMID- 12069253
TI  - Investigating humic acids in soils.

PMID- 12069254
TI  - Secondary ion mass spectrometry.

PMID- 12069255
TI  - Using humor to teach.

PMID- 12069256
TI  - Quantitative electroencephalography of medetomidine, medetomidine-midazolam and
      medetomidine-midazolam-butorphanol in dogs.
AB  - The purpose of this study was to evaluate the effects of the administration of an
      alpha2-adrenoceptor agonist alone and in combination with other derivatives on
      brain wave activity. In addition, the diagnostic values of the
      electroencephalogram (EEG) for judging the depth of the balanced anaesthesia with
      an alpha2-adrenoceptor agonist was evaluated. The treatments comprised 20
      microg/kg medetomidine (Me-20), 80 microg/kg medetomidine (Me-80), 20 microg/kg
      medetomidine and 0.5 mg/kg midazolam (Me-Mi) administered intramuscularly, and 20
      microg/kg medetomidine with 0.5 mg/kg midazolam and 0.1 mg/kg butorphanol (Me-Mi
      Bu). The EEG was recorded continuously at pre-administration, and at 7, 10, 20,
      30, 45 and 60 min after administration. The recorded data were analysed by
      separating the power spectrum into 1-3, 4-7, 8-13 and 14-30 Hz bands. Spectral
      edge analysis was used to calculate the spectral edge frequency 90 (SEF90) and
      the median edge frequency (MEF). Time-related changes in power spectrum analysis
      showed a significant increase in the Me-80 group in the 1-3 Hz band. The power
      for 1-3 Hz in the Me-80 group was significantly higher than in all the other
      groups. In the 14-30 Hz band, there was a significant reduction of power in all
      groups following administration of the agents. The SEF90 frequencies were
      significantly reduced in all groups except for the Me-20 group after
      administration of the agents. The SEF90 frequencies in the Me-20, Me-Mi and Me-Mi
      Bu were all significantly higher than those in the Me-80 group. However, there
      was no significant difference between the Me-20, Me-Mi and Me-Mi-Bu groups in any
      analyses. Our results demonstrated that the changes in quantitative EEG made by
      the Me-Mi-Bu and Me-Mi groups were similar to those made by Me-20 groups. Present
      results suggest that the EEG should be interpreted with caution in assessing the
      anaesthetic level in balanced anaesthesia in dogs.

PMID- 12069257
TI  - Equine endotoxemia: pathomorphological aspects of endotoxin-induced damage in
      equine mesenteric arteries.
AB  - To evaluate the effects of endotoxin on the morphology of the equine mesenteric
      vasculature, each of two thoroughbred horses were given two intravenous
      injections (24 h apart) of a sublethal dose of endotoxin (10 microg/kg). Each
      injection produced results similar to those of clinical cases of equine colic
      with obstructive nature of the loop of bowel: diarrhoea within 2 h after
      administration, followed by cessation of both faecal excretion and sounds of
      intestinal peristalsis. The most prominent morphological change was the
      development of moniliform appearance of small mesenteric arteries, in which there
      were contracted and dilated segments of the small mesenteric arteries. This was
      accompanied by parietal hyalinization and intramural and extramural haemorrhage.
      These mesenteric vascular changes appear to reflect dynamic vasoconstriction in
      the living animal, resulting in reduction of mesenteric and intestinal blood flow
      and possibly inducing alterations of gastrointestinal function such as cessation
      of intestinal peristalsis.

PMID- 12069258
TI  - Effect of energy density in the diet and milking frequency on hepatic long chain
      fatty acid oxidation in early lactating dairy cows.
AB  - The objective of this study was to examine the effects of diet energy density
      (high versus low) and increased milk yield, induced by increased milking
      frequency (two versus three times daily), on the hepatic status of
      triacylglycerol (TAG) and glycogen content and hepatic long chain fatty acid
      (LCFA) oxidation capacity in early lactation in a 2 x 2 factorial design. Forty
      multiparous Danish-Holstein dairy cows were used from 8 weeks before to 8 weeks
      after calving. Liver biopsies and blood samples were taken in weeks -2, 2, and 7
      from calving. The cows fed the high energy density diet, compared with the cows
      fed the low energy density diet, had an 18 and 28% higher milk production and net
      energy intake, respectively. Milk yield was increased by 10% when the cows were
      milked three times compared with twice daily. Complete (CO2 production) and
      incomplete (ketone body production) LCFA oxidation capacity in the liver were 35
      and 32% higher, respectively, and liver TAG content was 48% lower for the cows
      fed the high energy density diet compared with the low energy density diet.
      Overall there was no effect of milking frequency on liver parameters. However, a
      significant interaction between diet and milking frequency showed that the cows
      milked three times daily and fed the low energy density diet had the lowest liver
      LCFA oxidation (CO2 and ketone body) capacity. Furthermore, these cows had the
      numerically highest liver TAG content. The results for liver LCFA metabolism are
      discussed in relation to the plasma concentration of metabolites and insulin. In
      conclusion, cows in early lactation given a high energy density diet will, in
      general, have a lower risk of high TAG infiltration in the liver.

PMID- 12069260
TI  - Clinical effects of betamethasone and hyaluronan, and of defocalized carbon
      dioxide laser treatment on traumatic arthritis in the fetlock joints of horses.
AB  - The clinical effects of intra-articular betamethasone together with hyaluronan
      (betaM/HA) and treatment with a defocalized carbon dioxide laser on acute
      traumatic arthritis of the fetlock joint were assessed. The horses in these
      studies were selected using a thorough lameness examination, including intra
      articular anaesthesia abolishing the lameness. This investigation comprised an
      observer-blind study, including 10 sport horses (10 joints), and a prospective
      study, including 180 sport horses (333 joints). In both studies, the material was
      divided into two groups treated with either betaM/HA or a carbon dioxide laser.
      The treatment doses were 12 mg of betaM, 20 mg of HA or 60 J/cm2 of treated area.
      Convalescence before training was 21 days for both groups in the observer-blind
      study. In the prospective study, convalescence in the betaM/HA group was 21 days
      but was only 7 days for the laser-treated group. In the observer-blind study,
      three of five treated joints recovered in both cohorts. In the prospective study,
      the groups had significantly different recovery rates--68% of the betaM/HA
      treated joints and 80% of the carbon dioxide laser-treated joints. These results
      indicate that the defocalized carbon dioxide laser should be an applicable mode
      of treatment of acute traumatic synovitis in horses. However, the biochemical
      functions related to carbon dioxide laser treatment require further elucidation.

PMID- 12069259
TI  - Effects of malnutrition on the expression of daintain/AIF-1 in the gut mucosa of
      pigs.
AB  - The allograft inflammatory factor (AIF-1/daintain) is a hormone-like peptide
      produced by activated monocytic cells in a variety of traumatic, inflammatory and
      degenerative lesions. Gut-derived AIF-1 has been shown to modulate insulin
      production and to attenuate autoimmune diabetes. As the localization of this
      gastrointestinal peptide in the porcine duodenum is not known and the pig is a
      convenient model for the study of nutritional modulation of the mucosal immune
      compartment, we have localized expression of AIF-1 by immunohistology in the
      duodenum of either malnourished (energy and protein supply 50% of demands, n = 5)
      or optimally fed pigs (n = 5). AIF-1 macrophages were predominantly located at
      the villus tip. The number of positively stained cells per high-power field was
      significantly (P < or = 0.001) higher in the malnourished pigs (74.6 +/- 2.44;
      least square means +/- SEM) compared to optimally fed pigs (32.56 +/- 1.99). It
      is likely that the effect in malnourished pigs can be explained by a more
      pronounced antigen contact of macrophages due to loss of epithelial integrity.
      Thus, AIF-1 is a novel marker for the study of the nutritional regulation of the
      mucosal immune system of the pig. AIF-1 expression in the duodenum was further
      validated by polymerase chain reaction and sequencing. Surprisingly, we detected
      a slight deviation from the original sequence (probably representing an allelic
      variation) and an AIF-1 splice variant, previously not known to occur in pigs.

PMID- 12069261
TI  - Serum keratan sulphate as a cartilage metabolic marker in horses: the effect of
      exercise.
AB  - Keratan sulphate (KS) concentration in sera from resting horses and horses
      training daily on a racetrack was measured by an inhibition enzyme-linked
      immunosorbent assay (ELISA) using anti-equine KS antibody 1/14/16H9. For the in
      training horses, serum KS concentrations in 2-year-old-horses was significantly
      higher than 3- or 4-year-old-horses. A higher concentration of serum KS was found
      in the in-training group than in the long-term resting group in 2-year-old
      horses. Serum KS concentration increased remarkably immediately after training in
      healthy horses, and at 1, 5, 9 and 24 h after training remained at similar levels
      to the pre-training concentration. The results suggest that serum KS
      concentration could represent the situation of joint loading, induced by daily
      racetrack training, affecting the metabolic activities in joint cartilage.

PMID- 12069262
TI  - Use of immunocytochemical techniques in canine melanoma.
AB  - The staining patterns of the monoclonal antibodies S-100 and Melan-A in canine
      melanoma were assessed based on cytological specimens of six canine melanomas
      (four benign, two malignant). In addition, eight regional lymph nodes of the two
      dogs with malignant melanomas were stained using these markers. For reference,
      all specimens were also evaluated immunohistochemically using S-100 and Melan-A.
      To assess the immunocytochemical specificity of both antibodies, various canine
      tumours and normal tissues were stained. The immunocytochemical staining results
      of the canine melanomas and the regional lymph nodes showed high conformity with
      the immunohistochemical reactivity patterns for S-100 and Melan-A. The
      specificity of Melan-A was higher compared with S-100. Melan-A, in particular,
      may be helpful for the cytological diagnosis of canine melanoma.

PMID- 12069263
TI  - Biochemical intestinal parameters in pigs reared outdoors and indoors, and in
      germ-free pigs.
AB  - Intestinal microbial functions reflect cross-talk between a host and its flora,
      and external factors may influence these functions. The aim of this investigation
      was to follow the development of six biochemical microbial-related functions of
      piglets, raised outdoors (OPs) or indoors (IPs), from birth to slaughter age. The
      following parameters (microflora-associated characteristic; MAC) were
      consecutively measured at five different ages: production of short-chain fatty
      acids (SCFA), conversion of cholesterol to coprostanol and of bilirubin to
      urobilinogens, inactivation of trypsin, degradation of beta-aspartylglycine and
      of mucin. Additionally, four parameters (production of SCFA. conversion of
      cholesterol to coprostanol, inactivation of trypsin, degradation of beta
      aspartylglycine) were investigated in faecal samples from germ-free minipigs. The
      differences in MAC patterns between OPs and IPs were most pronounced at 20 days
      of age. Differences were found in the total amount of SCFAs, proportions of the
      acetic, propionic and butyric acids, conversion of bilirubin to urobilinogens,
      degradation of faecal tryptic activity and degradation of mucin. The values found
      in the minipigs were within the range of a germ-free animal characteristic (GAC)
      pattern. Our results show that environmental factors influence the development of
      some intestinal microbial functions in pigs.

PMID- 12069264
TI  - Investigations on blood coagulation in the green iguana (Iguana iguana).
AB  - The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin
      time, kaolin clotting time (KCT), dilute Russell's viper venom time (DRVVT) and
      reptilase time, as well as five different plasma fibrinogen assays [gravimetry,
      Jacobsson method (extinction at 280 nm), Millar method (heat precipitation),
      kinetic turbidometry, Clauss method] and resonance thrombography were performed
      in 26 clinically healthy green iguanas. All assays were carried out in comparison
      with pooled normal canine plasma. In iguana plasma, the PT [median (x0.50) = 453
      831 s, dependent on the reagent], APTT (x0.50 = 170-242 s, dependent on the
      reagent), thrombin time (x0.50 = 118 - > 1000 s, dependent on thrombin activity),
      KCT (x0.50 = 274 s), DRVVT (x0.50 = 349 s) and reptilase time (all samples > 1000
      s) were widely scattered at the limit of measurability. Only fibrinogen
      concentrations measured using the Jacobsson method (x0.50 = 4.40 g/l) correlated
      well (r = 0.91) with gravimetry (x0.50 = 4.22 g/l). The results of this study
      indicate a limited suitability and a confined diagnostic significance of the
      selected methods in the green iguana. This may be caused by the species
      specificity of certain components of the reagents used, as well as a less optimal
      test system, i.e. relationship of test reagent to clotting factor concentrations
      in iguana plasma.

PMID- 12069265
TI  - The influence of age and gender on haematological parameters in Lipizzan horses.
AB  - Haematological parameters [red blood cell count (RBC), white blood cell count
      (WBC), packed cell volume (PCV), haemoglobin concentration, mean cell volume
      (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration
      (MCHC)] in resting Lipizzan horses were determined for 143 stallions, 104 mares
      and 25 foals. The mean RBC and WBC values in Lipizzans were in the lower part of
      the normal range for warm-blooded horses. The mean PCV, MCV and MCH values were
      higher, but the mean haemoglobin concentration and MCHC values were lower than
      reported for other warm-blooded horses. In foals, the mean RBC, WBC, PCV,
      haemoglobin concentration and MCHC values were higher, whereas MCV and MCH were
      lower than in older animals. Results indicating a significant decrease in WBC (P
      < 0.01) and an increase in MCV, MCH and MCHC (P < 0.05) with increasing age are
      consistent with some other reports on warm-blooded horses. The age-related
      variations in RBC and PCV were less marked. Contrary to some reports, RBC (P <
      0.01), WBC and haemoglobin concentration (P < 0.001) were higher in Lipizzan
      stallions than in mares, but differences in MCHC, MCH and MCV were insignificant.
      The specific haematological values determined in Lipizzans are presumably a
      result of selection and should be taken into consideration when dealing with this
      race of horses.

PMID- 12069266
TI  - Exercise does not induce major changes in plasma muscle enzymes, creatinine,
      glucose and total proteins concentrations in untrained beagle dogs.
AB  - Changes in plasma creatinine (Pl-Creat), glucose, total proteins (Pl-TP),
      creatine kinase (Pl-CK), lactate dehydrogenase, aspartate aminotransferase and
      packed cell volume were evaluated in untrained Beagle dogs before, during and
      after a 60 min race at an average speed of 9 km/h. There was no major effect of
      exercise on those parameters except, when phases are compared, a slight increase
      of Pl-TP during exercise (max. + 6.4%), a moderate but after exercise (delayed
      increase of Pl-CK max. + 245%) and a slight decrease of Pl-Creat after exercise
      (max. -9.6%). It was therefore concluded that strenuous exercise in sedentary
      dogs did not induce major variations in any of routine plasma variables measured
      and would not lead to clinically relevant misinterpretation. However, for Pl-CK,
      the interpretation of repeated measures may be misleading if two samples are
      collected in the same animal before and after exercise.

PMID- 12069268
TI  - Overcoming immune tolerance during oral vaccination against Actinobacillus
      pleuropneumoniae.
AB  - In the preliminary study mice were vaccinated orally with Actinobacillus
      pleuropneumoniae microsphere oral vaccine. The lung and eye mucous membranes of
      these mice did not contain increased immunoglobulin A (IgA) following the initial
      oral vaccination, possibly through antibody persistence and the phenomenon of
      immune exclusion. A similar tendency was found for serum IgG. However, after the
      second vaccination, IgA still did not increase significantly, which could be
      attributed to immune suppression due to the possibility of the intestine inducing
      immune tolerance. Only the third vaccination overcame this effect and increased
      the level of IgA. In order to achieve a high systemic and local immune response
      this study attempted to overcome the initial tolerance to oral vaccination by
      using temporary immunosuppression, increasing antigen dose, and prolonging
      vaccine influence. Triamcinolone, used in the later productive phase of the
      immune response after the first and second vaccinations, but restricted in the
      inductive phase of the second and third vaccinations, could disable immune
      tolerance. Suppression of antibody production before the next induction of the
      immune response by an oral vaccine combined with suppression of cell-suppressor
      activity led to the creation of systemic immunity with the possibility of high
      levels of A. pleuropneumoniae growth inhibition. Increased antigen doses or
      durable consumption of antigen could overcome immune exclusion of antigen by
      primary antibodies. Even very low doses of vaccine (4.5 mg) could induce a
      primary immune response, and a dose increased by 10-fold for the second
      vaccination could overcome tolerance and maintain high systemic immunity. Chronic
      consumption of oral vaccine led to benefits in the quantity of local (not
      systemic) antibodies. The outcomes of the study can be adapted for practical oral
      immunization of pigs.

PMID- 12069267
TI  - Comparison of ITS profiling, REP- and ERIC-PCR of Salmonella Enteritidis isolates
      from Poland.
AB  - Thirty-one Salmonella Enteritidis strains isolated from chickens, broilers and
      hens were analysed by genotypic typing including REP-PCR. ERIC-PCR and ITS
      profiling (PCR-ribotyping). Analysis of DNA banding patterns generated by REP-PCR
      revealed the presence of 22 different genotypes, which were grouped by dendrogram
      analysis into three distinct lineages (maximum similarity approx. 50%). Each
      isolate of S. Enteritidis analysed by ERIC-PCR generated an individual DNA
      pattern. Again, these isolates could be divided into three distinct genomic
      groups (maximum similarity approx. 60%) by their ERIC-PCR fingerprints. REP- and
      ERIC-PCR were found to be more discriminatory for typing of S. Enteritidis than
      ITS profiling. Amplification of the 16S-23S rDNA spacer region gave nine
      different profiles of DNA, subdivided into two closely related groups by
      dendrogram analysis. In summary, data obtained by genotyping methods for S.
      Enteritidis isolates from regions located in the south-west and the central parts
      of Poland revealed an enormous heterogeneity among analysed samples, and proved
      that REP- and ERIC-PCR are highly discriminatory techniques, which can be used,
      in addition to conventional methods, in epidemiological studies of S. Enteritidis
      infections.

PMID- 12069269
TI  - The role of Isospora suis as a pathogen in conventional piglet production in
      Germany.
AB  - In order to evaluate the prevalence of Isospora suis in conventional piglet
      production in Germany, pooled faecal samples from 327 pig litters from 18 pig
      production units (20-320 sows each) were examined. At least 10 litters from each
      farm were investigated. I. suis was present on 83% of the farms and 42.5% of the
      litters, the infection rate being highest in the third week of age (48.2%). I.
      suis was found more frequently in samples of diarrhoea than in firm faeces (49.2%
      compared to 22.2%). Twenty naturally infected piglets from six of these farms
      underwent examination post mortem, including histology, virology and
      bacteriology. Histological examination revealed atrophy of the villi in various
      degrees, mild crypt hyperplasia, fusion of the villi, metaplastic epithelium,
      erosions and necrosis, especially in the medium and the posterior jejunum and in
      the ileum. Asexual and sexual developmental stages of the parasite were found in
      varying numbers in the epithelium of the whole of the small intestine. Bacteria
      and viruses were mostly excluded as the cause of diarrhoea, and it was concluded
      that I. suis was the primary pathogen inducing distinct changes and clinical
      symptoms of diarrhoea.

PMID- 12069270
TI  - The occurrence of pathogenic Listeria monocytogenes and antibodies against
      listeriolysin-O in buffaloes.
AB  - The occurrence of Listeria monocytogenes in meat and milk samples, and
      antilisteriolysin O (ALLO) antibodies in sera of buffaloes were studied.
      Isolation of the pathogen was attempted from the samples by selective enrichment
      in University of Vermont Medium and plating onto Dominguez-Rodriguez isolation
      agar. The pathogenicity of the isolates was tested by Christie, Atkins, Munch
      Petersen test and mouse inoculation test. Of 167 meat samples 2.4 and 10.17% were
      positive for L. monocytogenes and Listeria sp., respectively. Of the 64 milk
      samples 6.25 and 26.13% were positive for L. monocytogenes and Listeria sp.,
      respectively. A total of 284 serum samples were tested by listeriolysin O (LLO)
      based indirect enzyme-linked immunosorbent assay of which 25.35% were found to be
      seropositive. The culture positivity for L. monocytogenes and detection of ALLO
      did not show any agreement (kappa = 0.035). The prevalence of pathogenic L.
      monocytogenes in milk and meat and the occurrence of anti-LLO antibodies is of
      concern from the public health point of view.

PMID- 12069271
TI  - Studies on Streptococcus agalactiae isolated from bovine mastitis in Indonesia.
AB  - All 83 bacterial strains isolated from seven farms in three areas of the island
      of Java in Indonesia investigated in the present study could be identified as
      Streptococcus agalactiae. Identification was performed by cultural, biochemical
      and serological properties and by polymerase chain reaction amplification of
      species-specific parts of the gene encoding the 16S rRNA, the 16S-23S rDNA
      intergenic spacer region and the CAMP factor (cfb) gene. All isolates were
      unpigmented. almost all of the isolates had the serotype pattern II/X. Despite
      these similarities a macrorestriction analysis of the chromosomal DNA of the
      bacteria revealed no significant homologies of the DNA-fingerprints of the S.
      agalactiae from the various areas. This last finding might possibly indicate that
      a single ancestral unpigmented serotype II/X S. agalactiae clone was responsible
      for the mastitis situation on Java and had evolved separately in the various
      farms and regions.

PMID- 12069272
TI  - In vitro antimicrobial susceptibility of 183 Pseudomonas aeruginosa strains
      isolated from dogs to selected antipseudomonal agents.
AB  - During the years from 1993 to 2000, 183 strains of Pseudomonas aeruginosa were
      isolated from different pathological specimens originating from dogs.
      Antimicrobial susceptibility patterns against 10 antipseudomonal agents were
      obtained on 183 P. aeruginosa strains. In vitro antimicrobial susceptibility
      testing was performed using the disk diffusion method (Kirby-Bauer).
      Antimicrobial susceptibility profiles showed that among beta-lactam antibiotics,
      imipenem was the most active compound. Out of the 183 strains tested, 96.7% were
      sensitive to imipenem. Cefoperazone showed good in vitro activity against 86.9%
      of the tested strains. Against ceftazidime, 77.0% of strains showed sensitivity.
      An old penicillin, carbenicillin, gave only 71.6% sensitive strains. Sensitivity
      to amikacin was 87.4% and it was 83.1% to gentamicin. Pipimedic acid, a first
      generation quinolone, was the least active compound of all those tested, 47.0%
      were resistant. The in vitro sensitivity against enrofloxacin showed that 71.0%
      strains were sensitive and 26.2% showed resistance. Almost all strains tested,
      93.4%, were susceptible to ciprofloxacin and marbofloxacin. Besides imipenem, the
      quinolone antibiotics, marbofloxacin and ciprofloxacin were the most effective
      against P. aeruginosa strains isolated from dogs.

PMID- 12069274
TI  - Effects of prolonged exposure to low-dose fumonisin B1 in pigs.
AB  - From the point of view of human exposure, fumonisins (FB1, FB2, FB1, FB4), a
      relatively recently (1988) discovered and identified group of mycotoxins,
      represent one of the five most important mycotoxin groups causing human disease.
      In an earlier experiment studying the effects of relatively low doses (10, 20 and
      40 p.p.m.) of FB1 in weaned piglets, it was established that the 4-week feeding
      of 10 p.p.m. (mg/kg feed) FB1 produced mild pulmonary oedema. This suggested the
      importance of studies with even lower doses of the toxin to determine the
      tolerable limits. The objective of this experiment was therefore to study the
      effects of prolonged (8-week) exposure to still lower concentrations (0, 1, 5 and
      10 mg/kg feed) of FB1. The 8-week feeding of FB1 in low concentrations (1-10
      p.p.m.) did not cause clinical signs and significant performance impairment in
      pigs, but rendered irreversible the chronic changes that had already developed in
      the animals in a dose-dependent manner. Dissection revealed pathological
      alterations of the lungs in one of the animals given 1 p.p.m. (n = 4), in two
      animals exposed to 5 p.p.m. (n = 5), and in three animals given 10 p.p.m. (n =
      4). In all three treatment groups, proliferation of the connective tissue fibres,
      primarily of those around the lymphatic vessels, in the subpleural and
      interlobular connective tissue of the lungs, extending to the peribronchial and
      peribronchiolar areas, was seen. The results of this experiment call attention to
      the risk of prolonged low-dose toxin exposure, which has very important public
      health implications.

PMID- 12069273
TI  - In vitro effects of some steroidal hormones on the replication of avian
      pneumovirus.
AB  - The effects of testosterone, oestradiol, progesterone and cortisone on the in
      vitro replication of avian pneumovirus in tracheal organ cultures (TOC) were
      investigated. Samples of cell-associated and cell-free virus from TOC, grown in
      medium containing these hormones, were taken at selected intervals. Progesterone
      and cortisone caused a slight increase in cell-associated virus. Testosterone and
      oestradiol caused a slight delay and decrease in virus replication when compared
      with the controls. All groups shared the same time interval to reach peak cell
      free virus titre, 96 h post inoculation. In comparison with the controls, only a
      small drop (0.25-0.50 log10) in the peak of virus titre was observed in the
      hormone treated groups.

PMID- 12069276
TI  - Ultrastructural changes in caprine lungs infected with Mycoplasma capricolum
      subspecies capripneumonia.
AB  - Ultrastructural examination of the lungs from goats with natural infections with
      Mycoplasma capricolum subspecies capripneumonia, the causative agent of
      contagious caprine pleuropneumonia, revealed extensive hyperplasia of type II
      pneumocytes. Typically, these type II cells contained abundant numbers of
      osmiophilic lamellar bodies that had lost most of their characteristic lamellar
      ultrastructure. These findings were absent in healthy control goats.

PMID- 12069275
TI  - First report of post-weaning multisystemic wasting syndrome and porcine
      dermatitis and nephropathy syndrome in pigs in Greece.
AB  - Post-weaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and
      nephropathy syndrome (PDNS) are two recently described conditions of pigs at the
      late nursery and fattening stages. The aim of this short communication was to
      describe the first reported occurrence of these conditions and of porcine
      circovirus type 2 (PCV2) infection in Greece. The clinical signs, gross post
      mortem changes and histopathological changes observed in affected pigs, were
      similar to those previously described for both PDNS and PMWS. As in previous
      reports, the lesions were associated with PCV2 infection, which was demonstrated
      by immunohistochemical and in situ hybridization methods.

PMID- 12069277
TI  - The effect of tilmicosin on cardiac superoxide dismutase and glutathione
      peroxidase activities.
AB  - In this study, the effect of tilmicosin on cardiac superoxide dismutase and
      glutathione peroxidase activities was investigated. Forty male BALB/c mice were
      used as material. Ten mice served as a control group, and 30 mice were injected
      with tilmicosin (25 mg/kg body weight, subcutaneously, with a single injection).
      After drug administration, they were monitored for 3 days. Tilmicosin caused
      decreases in cardiac superoxide dismutase and glutathione peroxidase activities.

PMID- 12069278
TI  - Cerebrovascular disease and cognitive dysfunction.
AB  - As the general population ages, the progressive cognitive decline that occurs
      with aging and dementia is having a significant socioeconomic impact on society.
      Vascular dementia associated with cerebral vascular disease is now the third most
      common cause of dementia. Recent evidence has revealed a new and significant
      etiopathogenetic role of cerebrovascular pathology, as well as newly determined
      risk factors for the development of neurocognitive deficits and other forms of
      dementia including Alzheimer's disease. In this article, we summarize the
      experimental and clinical data linking cerebrovascular pathology to
      neurocognitive decline and dementia.

PMID- 12069279
TI  - Stent-assisted endoluminal revascularization for the treatment of intracranial
      atherosclerotic disease.
AB  - Since the inception of intravascular stents in the 1960s, marked technological
      advancements have yielded stents that can be navigated through tortuous cerebral
      vessels. Numerous applications for intracranial stenting are being developed at
      an exciting pace. One such application that has shown promise in several small
      series is the use of stents for endoluminal revascularization of severe
      intracranial stenosis that is refractory to medical therapy. Prior to the
      introduction of endovascular approaches for this condition, complex bypass
      procedures were often necessary to restore adequate blood flow to hypoperfused
      parenchyma. In the following article, we review endovascular techniques for
      stenting of intracranial atherosclerotic disease. Patient selection, vascular
      access, medical management, and future directions are discussed.

PMID- 12069280
TI  - Pros, cons, and current indications of open craniotomy versus gamma knife in the
      treatment of arteriovenous malformations and the role of endovascular
      embolization.
AB  - The successful treatment of an intracranial arteriovenous malformation poses both
      technical and conceptual problems to the neurosurgeon. Treatment decisions are
      made in light of current understanding of the natural history of these lesions.
      It is important to understand the pros, cons and current indication of open
      craniotomy vs. gamma knife in the treatment of arteriovenous malformations and
      the role of endovascular embolization. Surgical removal of an arteriovenous
      malformation is indicated when the operative risk is less than the morbidity and
      mortality associated with its natural history. The treatment goal of complete
      angiographic obliteration of arteriovenous malformations is achieved most
      effectively by microneurosurgery in low-grade lesions. Large lesions frequently
      require a combination of embolization and microsurgery. Although recent advances
      in technology and medical management have allowed previously inoperable
      arteriovenous malformations to be surgically excised, there is still a small
      group of arteriovenous malformations that cannot be excised safely due to their
      size and location. Stereotactic radiosurgery is clearly an important adjunct in
      the multimodality treatment approach for large arteriovenous malformations.
      Endovascular embolization can potentially increase safety and efficacy in the
      treatment of arteriovenous malformations when applied to selective cases with
      well-defined treatment goals.

PMID- 12069281
TI  - Transplantation of embryonal spinal cord nerve cells cultured on biodegradable
      microcarriers followed by low power laser irradiation for the treatment of
      traumatic paraplegia in rats.
AB  - This pilot study examined the effects of composite implants of cultured embryonal
      nerve cells and laser irradiation on the regeneration and repair of the
      completely transected spinal cord. Embryonal spinal cord nerve cells dissociated
      from rat fetuses and cultured on biodegradable microcarriers and embedded in
      hyaluronic acid were implanted in the completely transected spinal cords of 24
      adult rats. For 14 consecutive post-operative days, 15 rats underwent low power
      laser irradiation (780 nm, 250 mW), 30 min daily. Eleven of the 15 (73%) showed
      different degrees of active leg movements and gait performance, compared to 4
      (44%) of the 9 rats with implantation alone. In a controlgroup of seven rats with
      spinal cord transection and no transplantation or laser, six (86%) remained
      completely paralyzed. Three months after transection, implantation and laser
      irradiation, SSEPs were elicited in 69% of rats (p = 0.0237) compared to 37.5% in
      the nonirradiated group. The control group had no SSEPs response. Intensive
      axonal sprouting occurred in the group with implantation and laser. In the
      control group, the transected area contained proliferating fibroblasts and blood
      capillaries only. This suggests: 1. These in vitro composite implants are a
      regenerative and reparative source for reconstructing the transected spinal cord.
      2. Post-operative low power laser irradiation enhances axonal sprouting and
      spinal cord repair.

PMID- 12069282
TI  - Immunoglobulin G induces microglial superoxide production.
AB  - Activating microglias observed in the white matter after chronic cerebral
      hypoperfusion may play an important role in white matter changes (WMC).
      Microglial activation has been considered as a result of neuronal damage,
      however, recently it came to be recognized as a possible cause of the damage in
      various neurodegenerative diseases. The protective effect of an immunosuppressant
      on the WMC suggests that an immunologic reaction participates in the
      pathogenesis. Using a MCLA-dependent chemiluminescence method, we investigated
      the effect of immunoglobulin G (IgG) on microglial superoxide production. IgG
      stimulated microglias to produce superoxide. Microglial superoxide production by
      the Fab fragment of rat IgG was significantly less than that by the Fc fragment
      of rat IgG. The protective effect of an immunosuppressant on WMC may use the
      inhibiting effect on IgG. Our results suggest that if microglias come in contact
      with IgG in lesions, oxidative stress mediated by superoxide from microglial
      deteriorates WMC.

PMID- 12069283
TI  - Role of basic fibroblast growth factor in the course of cerebral vasospasm in an
      experimental model of subarachnoid hemorrhage.
AB  - The goal of this study was to investigate the relationship between basic
      fibroblast growth factor (bFGF) and the course of cerebral vasospasm after
      subarachnoid hemorrhage (SAH), using an immunohistochemical method. Female
      Sprague-Dawley rats were sacrificed by perfusion fixation 10 min, 6 h, 1, 2, 3,
      4, 7 or 14 days after a single intracisternal injection of fresh autologous
      arterial blood. Morphometric analysis of lumen cross-sectional areas of blood
      vessels were determined by computerized image analysis. Results were expressed as
      percent lumen patency, defined as the ratio of the area of vessel patency in SAH
      rats to the area of patency in control rats. An immunohistochemical analysis
      against bFGF was performed using the avidin-biotin-peroxidase technique. The
      immuno-reactivity of bFGF was observed with the aid of a light microscope and
      semiquantitatively graded. Basilar arterial spasm was greatest 10 min after SAH
      (mean decrease: 67.1% of the control values; p < 0.001). Subsequently, there was
      a significant degree of spasm of the artery for three days after SAH, followed by
      full recovery at day 4. A slight increase in immunoreactivity was observed in the
      intima only at 10 min and one day after SAH. In the media, immunoreactivity
      showed a biphasic pattern; a significant increase in immunoreactivity was
      observed at 10 min that persisted for two days after SAH. At three days after
      SAH, immunoreactivity in the media returned to the control level, but then
      gradually increased significantly to reach a maximum at 14 days after SAH while
      the vascular dimensions were normal. Immunohistochemical analysis failed to show
      a direct relationship between bFGF and the course of cerebral vasospasm in this
      rat single-hemorrhage model. However, the late phase upregulation of bFGF might
      lead to the vascular angiopathy, fibrosis or hyperplasia during the chronic stage
      of SAH.

PMID- 12069284
TI  - Endoscopic telerobotics for neurosurgery: preliminary study for optimal distance
      between an object lens and a target.
AB  - To overcome limited maneuverability and procedures in the endoscopic
      neurosurgery, and to utilize its maximum potential ability, the HUMAN (hyper
      utility mechatronic assistant) system has been developed. The system has a rigid
      three-dimensional endoscope with built-in three guiding-manipulators completely
      controlled as a slave robot by a surgeon in a remote place. To use this system
      most efficiently, we investigated the suitable distance between an object lens of
      the endoscope and a target. Actual working territory (AWT) and actual working
      angle (AWA) of the forceps in the endoscopical operative field (EOF) were
      measured by changing the distance between the lens and the target. AWT ratio
      (AWT/EOF) and AWA ratio (AWA/360) decreased from 58% to 12% and increased from
      39% to 85% respectively as the distance became longer. When the distance exceeds
      13 mm, AWA did not increase more than 85%, and AWT kept decreasing. For the
      effective use of the system, the optimal distance between the lens and the target
      should be within 13 mm, and the system will demonstrate its ability to the
      maximum at the distance of 8mm.

PMID- 12069285
TI  - Computer-based quantification of traditional chinese-, ear- and Korean hand
      acupuncture: needle-induced changes of regional cerebral blood flow velocity.
AB  - The purpose of this randomized, placebo-controlled, cross-over study was to
      investigate mean blood flow velocity (v(m)) of the ophthalmic (OA) and the middle
      cerebral (MCA) artery during traditional Chinese acupuncture (TCA), ear
      acupuncture (EA), Korean hand acupuncture (KHA) and placebo needling (PN) by
      simultaneous and continuous transcranial Doppler sonographic monitoring. We
      examined 20 healthy volunteers 19-45 years old (mean age +/- SD, 26.2 + 6.0
      years). Vm in OA was significantly increased during needling vision-related
      acupoints of TCA (p < 0.001), EA (p < 0.05) and KHA (p < 0.05), whereas
      nonsignificant alterations occurred in Vm of MCA. All subjects showed
      insignificant changes in mean arterial blood pressure. The study design does not
      allow to evaluate why and how the different acupuncture methods have an effect on
      the brain and eye, however it proves that acupuncture can provide scientifically
      measurable effects.

PMID- 12069286
TI  - Ischemic stroke prevention: an update on antiplatelet therapy.
AB  - Stroke is the third leading cause of mortality in the United States. As the
      leading cause of neurological deficits worldwide, stroke is associated with
      tremendous costs both to society and to the individuals and families stroke
      impacts. Antiplatelet agents have demonstrated efficacy in preventing recurrent
      atherothrombotic strokes and are the principal pharmacologic modality employed.
      With the recent development of the thienopyridines and the resurgence of
      dipyridamole, recommendations for antiplatelet therapy have undergone several
      iterations over the past decade. The focus of this review is to provide an update
      on the individual antiplatelet agents and recapitulate the current guidelines for
      antiplatelet selection and use in either transient ischemic attack or
      noncardiogenic ischemic stroke patients. Mechanisms of action, demonstrated
      efficacy, adverse effect profiles, and current consensus recommendations are
      reviewed for four conventional antiplatelet strategies, aspirin, ticlopidine,
      clopidogrel, and the combination of aspirin and extended-release dipyridamole.

PMID- 12069287
TI  - Antiproliferative effect of neomycin in glioma cells.
AB  - The angiogenic growth factor (AGF) family of signaling molecules has been
      implicated in normal development and in physiological process as well as in human
      malignancy. Since blockage of nuclear translocation of AGF in endothelial cells
      with neomycin resulted in inhibition of the growth factor capacity to induce
      angiogenesis, we treated glioma cells with neomycin and assessed its effects on
      cell proliferation. Administration of 10mM neomycin during two days resulted in a
      56% inhibition of glioma cells proliferation. This result may provide the basis
      for the development of a novel adjuvant therapeutic strategy forgliomas.

PMID- 12069288
TI  - Vasospasm following subarachnoid hemorrhage: evidence against functional
      upregulation of Rho kinase constrictor pathway.
AB  - This study tested the hypothesis that vasospasm due to subarachnoid hemorrhage
      involves the functional upregulation of Rho kinase. Spasm of the rabbit basilar
      artery was achieved using a double hemorrhage model, which we previously
      demonstrated was endothelin-1 dependent. In situ effects of agents were
      determined by direct measurement of vessel diameter following their suffusion in
      a cranial window. Y-27632, a Rho kinase inhibitor, relaxed the spasm. However,
      relaxations to Y-27632 were not significantly greater in endothelin-1 constricted
      spastic vessels initially relaxed with the endothelin converting enzyme
      inhibitor, phosphoramidon, as compared to endothelin-1 constricted control
      vessels. These results suggest that, at least in the rabbit double subarachnoid
      hemorrhage model, vasospasm does not involve the functional upregulation of Rho
      kinase.

PMID- 12069289
TI  - Outcome of extracranial cervicocephalic arterial dissections: a follow-up study.
AB  - Cervicocephalic arterial dissections (CCAD) are an increasingly recognized cause
      of ischemic stroke in young adults. Various treatments have been suggested but no
      controlled trial has ever been performed. Medical treatment has included
      anticoagulant or platelet antiaggregant therapy. Surgical correction has been
      proposed for selected patients who have failed medical therapy. Percutaneous
      balloon angioplasty and stenting have been increasingly used in some patients,
      although long-term results are unknown. The objective of the study was to review
      our recent experience with the management and outcome of extracranial CCAD. We
      identified 27 patients with extracranial CCAD who were evaluated, treated and/or
      followed by our Stroke Service from September 1995 to August 2001. Clinical
      presentation, diagnostic evaluation, management, and outcome were reviewed. There
      were 15 men (56%) and 12 women (44%) with mean ages of 38 and 43 years
      respectively. Diagnosis was made by cerebral angiography in 15 (56%) patients and
      by MRI/MRA only in 12 (44%) patients. Twenty-two patients had spontaneous and
      five had traumatic extracranial CCAD. Most common associated disorders were
      arterial hypertension (37%) and migraine (26%). One patient presented only with a
      painful post-ganglionic Horner syndrome, another patient with neck pain and post
      ganglionic Horner syndrome, another patient solely with protracted unilateral
      headaches, three with transient ischemic attacks (TIA), and 21 with ischemic
      strokes. The internal carotid artery (ICA) was the most frequently involved
      vessel (63%), followed by the vertebral artery (30%, and multivessel involvement
      in two patients (7%). Eighteen patients received anticoagulant therapy and nine
      platelet anti-aggregants. Follow-up extended from 2 to 115 months, with a mean of
      58 months. At the end of follow-up, 23 (85%) patients had either no disability or
      only minor sequelae (modified Rankin score: 0 to 1), and four (15%) patients had
      moderate limitations (modified Rankin score: 2 to 3). Two patients had a
      recurrent ischemic stroke, one unrelated to recurrent CCAD, and the other
      following percutaneous balloon angioplasty/stenting for treatment of a persistent
      vertebral artery pseudoaneurysm. Most CCAD involved the extracranial ICA. The
      clinical presentation is variable, most patients having an ischemic stroke or
      TIAs. The short- and long-term outcome are usually favorable with either
      anticoagulant or platelet antiaggregant therapy. A medical initial approach to
      the management of extracranial CCAD is recommended for most patients.

PMID- 12069290
TI  - The effects of early insulin treatment combined with thrombolysis in rat embolic
      stroke.
AB  - The therapeutic effect of insulin alone or insulin combined with 30 min delayed
      thrombolytic therapy was investigated in rats embolized in the right hemisphere
      with a fibrin clot made from autologous blood. Animals were killed seven days
      after embolization and the infarct volumes were measured in % of the affected
      hemisphere. Mortality was calculated as the number of animals dying spontaneously
      before the scheduled euthanasia. The median infarct volume in control animals (n
      = 12) was 24%. Insulin (3 IU kg(-1)) was given subcutaneously 15 min, 3 h, and 24
      h after embolization (n = 12) and reduced median infarct volume to 11%. Human
      recombinant tissue plasminogen activator, 8 mg kg(-1), was infused intravenously
      during 45 min starting 30 min after embolization (n = 14), and the median infarct
      volume was 18% in this group. When the two treatments were combined, the median
      infarct volume was reduced to 11% (n = 14). The infarct volumes in the treatment
      groups were not significantly different from controls (p = 0.62, Kruskal Wallis
      test). Mortality rates increased from 0% among controls to 47% (p = 0.01) in the
      insulin alone and 38% (p = 0.02) in the combination therapy group. In conclusion,
      insulin treatment aiming at blood glucose levels around 2-4 mmol l(-1) was
      detrimental to clinical outcome causing significantly increased mortality.

PMID- 12069291
TI  - Effect of neutralization of rat IL-6 bioactivity on collateral blood supply from
      retrograde flow via cortical anastomoses in the rat central nervous system.
AB  - The purpose of this study was to determine whether neutralization of rat
      interleukin-6 (IL-6) bioactivity increases the collateral blood supply from
      retrograde flow via the major middle cerebral artery branches after experimental
      middle cerebral artery occlusion in the rat. Seventy rats were randomly allocated
      to four main groups: Group I (n = 10) consisted of normal controls; Group II (n =
      20) underwent craniectomy only; Group III (n = 20) was subjected to middle
      cerebral artery occlusion; and Group IV (n = 20) underwent middle cerebral artery
      occlusion and treatment with anti-rat IL-6 antibody. Half of the rats from each
      of Groups II, III and IV were killed at 24 h and the other half at 72 h after
      craniectomy alone or occlusion. A single dose of antibody did not affect middle
      cerebral artery caliber, but administration of three doses resulted in a
      significant increase in the diameter of middle cerebral artery compared to the
      findings in the corresponding occlusion-only groups. The results suggest that
      neutralization of rat IL-6 bioactivity in long-term recovery increases the
      collateral blood supply from retrograde flow via cortical anastomoses after
      experimental arterial occlusion in the rat brain.

PMID- 12069292
TI  - The easiest person to fool.

PMID- 12069293
TI  - A methodology for inferring the causes of observed impairments in aquatic
      ecosystems.
AB  - Biological surveys have become a common technique for determining whether aquatic
      communities have been injured. However, their results are not useful for
      identifying management options until the causes of apparent injuries have been
      identified. Techniques for determining causation have been largely informal and
      ad hoc. This paper presents a logical system for causal inference. It begins by
      analyzing the available information to generate causal evidence; available
      information may include spatial or temporal associations of potential cause and
      effect, field or laboratory experimental results, and diagnostic evidence from
      the affected organisms. It then uses a series of three alternative methods to
      infer the cause: Elimination of causes, diagnostic protocols, and analysis of the
      strength of evidence. If the cause cannot be identified with sufficient
      confidence, the reality of the effects is examined, and if the effects are
      determined to be real, more information is obtained to reiterate the process.

PMID- 12069294
TI  - Determining probable causes of ecological impairment in the Little Scioto River,
      Ohio, USA: part 1. Listing candidate causes and analyzing evidence.
AB  - The Little Scioto River in north-central Ohio, USA, is considered to be
      biologically impaired based on the results of fish and invertebrate surveys. The
      causes for these impairments were evaluated by means of a formal method. Two of
      the impairments identified on the stream reach were characterized in detail to
      support the causal assessment. A list of six candidate causes was developed that
      included habitat alteration, polycyclic aromatic hydrocarbon contamination,
      metals contamination, low dissolved oxygen, ammonia toxicity, and nutrient
      enrichment. Evidence for the causal evaluation was developed with data from the
      site that associated each candidate cause with the biological responses. Evidence
      was also developed that drew on data from other locations and laboratory studies,
      including comparisons of site exposures with screening values and criteria. The
      formal method increased the transparency of the assessment; candidate causes were
      clearly listed and the pathways by which they may have produced effects were
      shown. Analysis of the evidence maximized the utility of available data, which
      were collected as part of monitoring and research programs rather than to
      specifically support a causal assessment. This case study illustrates how the
      stressor identification method can be used to draw conclusions from available
      data about the most likely causes of impairment and to show what additional
      studies would be useful.

PMID- 12069295
TI  - Determining the causes of impairments in the Little Scioto River, Ohio, USA: part
      2. Characterization of causes.
AB  - Two stream reaches in the Little Scioto River (OH, USA) were characterized for
      the causes of impairments measured at two locations. By inductive inference, six
      candidate causes were winnowed down to three and five candidate causes for each
      of the two stream reaches. Using a formal strength-of-evidence process, a single
      cause was determined. At the most upstream location, habitat alterations,
      including fine-textured substrates and low DO, were characterized as the probable
      causes for an increased percentage of anomalies of fish, a decreased percentage
      of mayflies, and an increased percentage of tolerant macroinvertebrates. An
      increase in the relative weight of fish was attributed to an artificially narrow,
      deepened channel. Approximately 2 km downstream, polycyclic aromatic hydrocarbon
      (PAH)-contaminated sediments were identified as the cause for both fish and
      macroinvertebrate impairments. Causal characterization using first elimination
      and then a strength-of-evidence approach narrowed and defined the causes of
      ecological impairment even in this situation, where many complex and interacting
      candidate causes existed. Applying a formal method highlighted types of data and
      associations that can strengthen and present a more convincing determination of
      the causes of impairment.

PMID- 12069296
TI  - Integrating observational and experimental approaches to demonstrate causation in
      stream biomonitoring studies.
AB  - Routine biomonitoring of aquatic ecosystems generally is performed with the
      intent of demonstrating a causal relationship between stressors and responses.
      However, because it is impossible to eliminate other potential explanations for
      observed spatiotemporal correlation between stressors and responses,
      demonstrating causal relationships is highly tenuous in descriptive studies. In
      this research we show how results of descriptive and experimental approaches can
      be integrated to demonstrate a causal relationship between heavy metals and
      benthic community responses in a Rocky Mountain stream (CO, USA). By using a
      stressor identification process, we show that effects and exposure data collected
      from a contaminated site (Arkansas River, CO, USA) can be integrated with
      experimental data to support causal arguments. Analysis of the spatial co
      occurrence of metals and benthic community responses in the Arkansas River
      provided support for the hypothesis that metals caused alterations in benthic
      community structure. Exposure pathways were quantified by measuring metal
      bioaccumulation in caddisflies (Trichoptera) collected upstream and downstream
      from metal inputs. A long-term (10-year) monitoring study showed that reductions
      in metal concentrations corresponded with improvements in benthic communities.
      These results were supported by microcosm and field experiments that quantified
      concentration-response relationships between heavy metals and benthic community
      composition. Consistency of these responses was demonstrated by comparing results
      to a spatially extensive survey of metal-polluted streams in Colorado. Our study
      demonstrates the power of integrating descriptive and experimental approaches for
      developing causal arguments in ecological assessments.

PMID- 12069297
TI  - Assessing relationships between human land uses and the decline of native
      mussels, fish, and macroinvertebrates in the Clinch and Powell River watershed,
      USA.
AB  - The free-flowing Clinch and Powell watershed in Virginia, USA, harbors a high
      number of endemic mussel and fish species but they are declining or going extinct
      at an alarming rate. To prioritize resource management strategies with respect to
      these fauna, a geographical information system was developed and various
      statistical approaches were used to relate human land uses with available fish,
      macroinvertebrate, and native mussel assemblage data. Both the Ephemeroptera,
      Plecoptera, Trichoptera (EPT) family-level index, and the fish index of biotic
      integrity (IBI) were lowest in a subwatershed with the greatest coal mining
      activity (analysis of variance [ANOVA], p < 0.05). Limited analyses in two other
      subwatersheds suggested that urban and agricultural land uses within a specified
      riparian corridor were more related to mussel species richness and fish IBI than
      land uses in entire catchments. Based on land uses within a riparian corridor of
      200 m x 2 km for each biological site in the watershed, fish IBI was inversely
      related to percent cropland and urban area and positively related to pasture area
      (stepwise multiple regression, R2 = 0.55, p < 0.05). Sites less than 2 km
      downstream of urban areas, major highways, or coal mine activities had a
      significantly lower mean IBI value than those more than 2 km away (ANOVA, p <
      .05). Land use effects included poorer instream cover and higher substrate
      embeddedness (t test, p < 0.05). Weaker land use relationships were observed for
      EPT and mussel species richness. Episodic spills of toxic materials, originating
      from transportation corridors, mines, and industrial facilities, also have
      resulted in local extirpations of native species. particularly mussels. The
      number of co-occurring human activities was directly related to stream elevation
      in the Clinch River, with more human land uses in headwater areas. Approximately
      60% of known U.S. Fish and Wildlife mussel concentration sites in the watershed
      are located within 2 km of at least two land use sources identified as
      potentially stressful in our analyses. Our results indicate that a number of land
      uses and stressors are probably responsible for the decline in native species.
      However, protection of naturally vegetated riparian corridors may help mitigate
      some of these effects.

PMID- 12069298
TI  - Use of physical, chemical, and biological indices to assess impacts of
      contaminants and physical habitat alteration in urban streams.
AB  - Human activities in urban areas can lead to both chemical pollution and physical
      alteration of stream habitats. The evaluation of ecological impacts on urban
      streams can be problematic where both types of degradation occur. Effects of
      contaminants, for example, may be masked if stream channelization, loss of
      riparian vegetation, or other physical stressors exert comparable or larger
      influences. In the Aberjona watershed (near Boston, MA, USA), we used physical,
      chemical, and biological indices to discern the relative impacts of physical and
      chemical stressors. We used standard protocols for assessing the biological
      condition of low-gradient streams, sampling macroinvertebrate communities from
      several different habitat types (e.g., overhanging bank vegetation, undercut bank
      roots, and vegetation on rocks). We strengthened the linkage between chemical
      exposure and macroinvertebrate response by measuring metal concentrations not
      only in sediments from the stream bottom but also in the vegetative habitats
      where the macroinvertebrates were sampled. Linear regression analysis indicated
      that biological condition was significantly dependent (95% confidence level) on
      contaminants in vegetative habitats, but not on contaminants in sediments from
      the stream bottom. Biological condition was also significantly dependent on
      physical habitat quality; regression analysis on both contaminants and physical
      quality yielded the best regression model (r2 = 0.49). Similar biological
      impairment was observed at sites with severe contamination or physical impairment
      or with moderate chemical and physical impairment. These results have
      implications for the management of urban streams.

PMID- 12069299
TI  - Predicting levels of stress from biological assessment data: empirical models
      from the Eastern Corn Belt Plains, Ohio, USA.
AB  - Interest is increasing in using biological community data to provide information
      on the specific types of anthropogenic influences impacting streams. We built
      empirical models that predict the level of six different types of stress with
      fish and benthic macroinvertebrate data as explanatory variables. Significant
      models were found for six stressor factors: stream corridor structure; siltation;
      total suspended solids (TSS), biochemical oxygen demand (BOD), and iron (Fe);
      chemical oxygen demand (COD) and BOD; zinc (Zn) and lead (Pb); and nitrate and
      nitrite (NOx) and phosphorus (P). Model R2 values were lowest for the siltation
      factor and highest for TSS, BOD, and Fe. Model R2 values increased when spatial
      relationships were incorporated into the model. The models generally performed
      well when applied to a random subset of the data. Performance was more mixed when
      models were applied to data collected from a previous time period, perhaps
      because of a change in the spatial structure of these systems. These models may
      provide a useful indication of the levels of different stresses impacting stream
      reaches in the Eastern Corn Belt Plains ecoregion of Ohio, USA. More generally,
      the models provide additional evidence that biological communities can serve as
      useful indicators of the types of anthropogenic stress impacting aquatic systems.

PMID- 12069300
TI  - Fate of tributyltin in a created tidal wetland.
AB  - The ability of Spartina alterniflora to degrade tributyltin (TBT) in contaminated
      dredge spoils was investigated in a created wetland at Little Creek Naval
      Amphibious Base in Norfolk, Virginia, USA. Concentrations of TBT up to 250 ng/g
      did not inhibit S. alterniflora growth over a 16-month period. Disappearance
      rates of TBT in vegetated and unvegetated treatments were similar, with half
      lives of 300 to 330 d. Disappearance rates were not constant, but they were
      correlated to temperature changes and were possibly due to microbial degradation
      within the sediment. Of the initial amount of TBT in the sediment, only 0.4%
      accumulated in S. alterniflora biomass. Uptake of TBT by S. alterniflora was
      greatest in belowground biomass (43 ng/g). During plant senescence, most of the
      TBT was retained in the detrital material. Whereas S. alterniflora did not
      expedite the degradation of TBT, using TBT-contaminated dredge spoils to create
      wetlands is plausible. However, this should only be undertaken after further
      investigation into the potential for plant biomass to become a biovector for TBT.

PMID- 12069301
TI  - Methyltransferase: an enzyme assay for microbial methylmercury formation in
      acidic soils and sediments.
AB  - Methylmercury (MeHg) is a highly toxic form of mercury that bioaccumulates in
      aquatic food chains. However, methods to reliably identify sites of MeHg
      formation or to quantify MeHg production require the use of isotopic tracers,
      which limits their use. In this paper, a method is presented to quantify the
      methylation of mercury by a methyltransferase pathway. This methyltransferase
      pathway is one of the biochemical pathways responsible for biological mercury
      methylation. Protein is extracted from environmental samples, and mercury
      methyltransferase (HgMT) activity of soil extracts is calculated by assessing
      increases in methyltransferase activity induced by Hg addition. In enzyme
      extracts from pure cultures or soil samples, HgMT activity correlated with net
      MeHg production and Hg consumption, suggesting that HgMT activity can be used to
      estimate MeHg production in field samples. Over the course of a three-month
      period in a freshwater wetland, HgMT activity correlated with net MeHg
      concentrations (r2 = 0.55; p < 0.057). Furthermore, HgMT activity predicted (r2 =
      0.80; p < 0.01) gross MeHg formation in freshwater wetlands as well as in
      laboratory microcosms calculated using previously published rate constants. Our
      results show that a methyltransferase assay, in combination with demethylation
      estimates, accurately predicts MeHg formation under field and laboratory
      conditions. This assay does not require the use of mercury added to field samples
      to estimate activity but rather estimates the biological activity present in the
      soil by quantifying the amount of enzyme present in the soil. Such an assay is
      well suited for use in field surveillance programs assessing MeHg formation in a
      variety of environments.

PMID- 12069302
TI  - Acute toxicity of triorganotin compounds: different specific effects on the
      energy metabolism and role of pH.
AB  - Triorganotin compounds exhibit several modes of toxic action on the energy
      metabolism in energy-transducing membranes. The inhibition of the adenosine
      triphosphate (ATP) synthase and the hydroxide/chloride-antiport have been
      extensively investigated, but debate still exists on whether further mechanisms
      are relevant. In this work, two possible further effects have been investigated:
      inhibition of the bc1 complex and the hydroxide uniport, and in addition, the
      overall inhibition of the ATP synthesis was investigated in chromatophores of the
      photosynthetic purple bacterium Rhodobacter sphaeroides at pH = 7.5 and pH = 6.1.
      Experimental conditions were chosen in order to exclude the hydroxide/anion
      antiport as a possible effect. Inhibition of the cytochromes bc1 complex was
      detected, but at such high concentrations that it is not relevant for acute
      toxicity. Tributyltin was found to induce a decrease of the membrane potential,
      which can be attributed to a hydroxide uniport, whereas for triphenyltin no such
      activity was observed. For both compounds, inhibition of the ATP synthesis was
      higher at pH = 6.1 than at pH = 7.5. Also the hydroxide uniport activity of
      tributyltin was higher at lower pH. The contribution of the hydroxide uniport of
      tributyltin to the overall inhibition of the ATP synthesis cannot be quantified;
      however, hydroxide uniport occurred in the same concentration range as inhibition
      of the ATP synthesis. For triphenyltin, inhibition of the ATP synthesis can be
      attributed to the inhibition of the ATP synthase. It was concluded that
      chromatophores of R. sphaeroides are a useful system to discriminate various
      effects of toxicants on the energy metabolism of a cell.

PMID- 12069303
TI  - Postexposure feeding depression: a new toxicity endpoint for use in laboratory
      studies with Daphnia magna.
AB  - In situ bioassays with daphnids currently employ lethality as an endpoint, and
      although sublethal responses (reproduction and feeding rate) can be measured in
      the field, such endpoints pose major practical challenges. Previous studies have
      indicated that Daphnia magna exposed to toxic substances can exhibit delayed
      recovery in feeding behavior (postexposure feeding depression). This simple,
      robust response has the potential to be an ecologically relevant and potentially
      diagnostic endpoint. This study developed and tested the use of postexposure
      feeding depression as a toxicity endpoint in the laboratory environment. First,
      replicate numbers were manipulated to produce statistically reliable results.
      Second, postexposure feeding depression in D. magna was studied under laboratory
      conditions, by employing toxic substances with differing modes of action.
      Although most substances caused feeding inhibition during direct exposure, not
      all substances produced postexposure feeding depression. However, the use of
      lethality as a supplementary endpoint provided an alternative measure when no
      feeding depression was apparent after exposure. In combination, these endpoints
      offer a potentially more sensitive, ecologically relevant alternative to the use
      of lethality alone for in situ bioassay studies.

PMID- 12069304
TI  - Antifungal activity of some trityl-based synthetic dyes.
AB  - The fungicidal activity of 10 trityl dyes and six reference compounds was
      determined on 36 fungal strains, and the data matrix was evaluated separately by
      principal component analysis (PCA) and by spectral mapping technique (SPM). The
      dimensionality of the maps of the principle component loadings and variables and
      the selectivity maps were reduced to two by varimax rotation and by nonlinear
      mapping. Calculations proved that both the strength and selectivity of the
      fungicidal activity of trityl dyes considerably depended on the chemical
      structure of the dye and on the type of fungi. Both PCA and SPM were suitable for
      evaluation of the antifungal activity of dyes; however, the strength and
      selectivity of the fungicidal effect can be separated only by SPM. Due to its
      advantageous application parameters, use of SPM in future quantitative structure
      activity relationship studies is highly recommended.

PMID- 12069305
TI  - Extractable substances (anionic surfactants) from membrane filters induce
      morphological changes in the green alga Scenedesmus obliquus (Chlorophyceae).
AB  - The effect of filtration of medium through different kinds of filters (glass
      fiber, mixed esters of cellulose and nitrocellulose) on the morphology in the
      green alga Scenedesmus obliquus was examined. Several compounds potentially
      released from membrane filters were further investigated, and among them, two
      anionic surfactants were found to be morphologically active. Exposure to the
      anionic surfactants resulted within 2 d in the transformation of unicellular
      populations of Scenedesmus in populations dominated by colonies. Growth rates
      between control and surfactant-exposed populations were identical, and the
      morphological effect occurred at surfactant concentrations far below the reported
      no-observed-effect concentration for growth inhibition, stressing the need for
      inclusion of morphological appearance of Scenedesmus in algal toxicity testing to
      improve the assessment of ecological risks.

PMID- 12069306
TI  - Bioavailability of metals to the amphipod Monoporeia affinis: interactions with
      authigenic sulfides in urban brackish-water and freshwater sediments.
AB  - Could reduced eutrophication be a potential environmental threat because of
      increased mobility and bioavailability of trace metals? This question was
      addressed by oxygenating intact sediment cores, varying in redox potential and
      salinity, in a test system containing the amphipod Monoporeia affinis. Results
      show a low mobility of metals during oxygenation, and despite high concentrations
      of metals in sediments, only Pb showed a notable degree of bioaccumulation.
      Cadmium was bioaccumulated particularly in freshwater sediment, and body burden
      of Cd was related to salinity, porewater, and sediment concentrations. Despite
      high sediment and porewater concentrations of Cu and Zn, no relationship was
      recorded to body burden. For three of four tested metals, Cd, Pb, and Zn, metals
      in sediment were more important for body burdens in amphipods as compared to
      metals in porewater. Food, rather than interstitial water, therefore seems to be
      the main route of metal contaminants to these amphipods. Furthermore, this
      observed low release of metals from sediments and low body burden significance of
      porewater metals indicate that ameliorated oxygen conditions in contaminated
      sediments may be regarded as a minor environmental threat for one of the most
      important Baltic benthic organisms.

PMID- 12069307
TI  - Purification and identification of a tributyltin-binding protein from serum of
      Japanese flounder, Paralichthys olivaceus.
AB  - Tributyltin (TBT) is an industrial chemical used as an antifoulant in marine
      environments. Previously, we reported that TBT accumulates in the serum or plasma
      of some fishes and is bound to a high molecular weight compound in the serum of
      the Japanese flounder, Paralichthys olivaceus. In this study, we succeeded in
      purifying the TBT-binding protein (TBT-bp) from the serum of Japanese flounder by
      using gel filtration chromatography, anion exchange chromatography, and
      polyacrylamide gel electrophoresis, with a 2.6% yield and a 77-fold purification.
      The molecular mass of TBT-bp was approximately 46.5 kDa on sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and its isoelectric point was approximately
      3.0 on isoelectric focusing-polyacrylamide gel electrophoresis. The TBT-bp
      contained 42% N-glycan. The cDNA nucleotide sequence of TBT-bp was determined by
      reverse transcription-polymerase chain reaction of Japanese flounder liver, and
      we deduced a sequence of 191 amino acids of mature TBT-bp. No sequence identical
      to the TBT-bp amino acid sequence was found within the SWISS-PROT
      (http://www.nig. ac.jp/) protein database; however, a lipocalin-like sequence
      pattern was observed. We concluded that the TBT-bp was a novel protein that has
      not yet been reported, although some DNA sequences from expressed sequence tags
      (ESTs) of Japanese flounder liver had a high identity. A high expression level of
      TBT-bp gene was found in the liver, but the gene was slightly detectable in the
      kidney and brain.

PMID- 12069309
TI  - Inhibition of digestive enzyme activities by copper in the guts of various marine
      benthic invertebrates.
AB  - Digestive systems of deposit and suspension feeders can be exposed to high
      concentrations of copper (Cu) by ingestion of contaminated sediments. We assessed
      a potential impact of this Cu exposure on digestive enzyme activities in a wide
      range of benthic organisms by monitoring enzyme activities in their gut fluids
      during in vitro titrations with dissolved Cu, which mimics Cu solubilization from
      sediments. Increasing Cu inhibited digestive protease activities at threshold
      values, which varied widely among organisms, from 8 microM for an echinoderm to
      0.4 M for an echiuran. More Cu was required to inhibit proteases in guts
      containing higher amino acid concentrations because strong Cu-binding sites on
      amino acids prevent Cu interaction with the enzymatically active sites. Threshold
      Cu concentrations were similar for proteases, esterases, lipases, and alpha- and
      beta-glucosidases, suggesting the same inhibition mechanism. Copper was less
      effective at inhibiting enzymes at lower pH, suggesting that protons can compete
      with Cu ion for binding to enzymatically active sites or that enzyme conformation
      is less vulnerable to Cu inhibition at lower pH. These results lead to the
      counterintuitive conclusion that deposit feeders with low enzyme activity, low
      amino acid concentration, and high pH values are most vulnerable to harm from
      sedimentary Cu by this mechanism, although they solubilize less sedimentary Cu
      than their counterparts with high enzyme activity, high amino acid
      concentrations, and low gut pH. In general, digestive systems of echinoderms may
      therefore be more susceptible to Cu contamination than those of polychaetes, with
      various other phyla showing intermediate susceptibilities. If threshold Cu values
      are converted to solid-phase sedimentary Cu concentrations, the thresholds are at
      least consistent with Cu loadings that have been observed to lead to biological
      impacts in the field.

PMID- 12069308
TI  - Fate and bioaccumulation of isoproturon in outdoor aquatic microcosms.
AB  - To gain information concerning the ecotoxicity of isoproturon (IPU) on aquatic
      ecosystems, six experimental ponds of 5 m3 each were studied. All the experiments
      were conducted during the summer over two years. Three different types of
      ecosystems were tested in 1994 and one type of ecosystem was selected and
      repeated in 1995 with three replicates. In each case, the initial concentration
      of IPU contamination was set at 10 microg/L. The IPU concentration was determined
      in the water column and in different species (mainly plants) of the microcosms. A
      first-order kinetic decrease in IPU concentration was observed in 1994, with half
      life ranging from 15 to 35 d, depending on the microcosms. This relatively fast
      decrease was also confirmed in 1995, but it reached a constant value after two
      months. A high variability of the IPU concentration was observed in exposed
      plants, with bioconcentration factors ranging from 100 to 1,200 with large
      coefficients of variation. The observed plant bioconcentration factors are higher
      than those predicted by usual numerical models, probably due to the specific
      binding of IPU on one protein of the photosynthetic apparatus. Our data show that
      bioconcentration does not occur in mollusks but is important in photosynthetic
      organisms. Plant bioconcentration and microbial biodegradation are the main
      processes involved in the IPU decay in our outdoor aquatic microcosms.

PMID- 12069310
TI  - Assessing the genotoxicity of chronic environmental irradiation by using
      mitochondrial DNA heteroplasmy in the bank vole (Clethrionomys glareolus) at
      Chornobyl, Ukraine.
AB  - This study was designed to investigate whether or not chronic exposure to
      Chornobyl radiation poses a molecular genetic risk to mammals by examining a
      relatively rapidly evolving genetic system, mitochondrial DNA (mtDNA). More mtDNA
      mutations (approximately 19%) and an increase in mtDNA heteroplasmy
      (approximately 5%) occurred in the cytochrome b gene of an exposed mother-embryo
      set when compared to a relatively unexposed mother-embryo set. However, this
      increase was not statistically significant (p > 0.05). Our results, in
      conjunction with previous molecular genetic research on small mammals from
      Chornobyl, suggest that chronic exposure to environmental ionizing radiation does
      not increase the number of nucleotide substitutions, as predicted by studies
      using acute or subacute exposures. Thus, cumulative models of radiation risk
      would not appear to follow simple linear functions derived from high doses and
      dose rates. The equivocal nature of research regarding the effects of the
      Chornobyl accident indicates that future research is warranted such that models
      of chronic environmental exposure can be developed or refined. Although
      additional study is required to properly validate mtDNA heteroplasmy as a useful
      effect biomarker, examination of these data does not indicate that a significant
      risk to mtDNA exists in native rodents chronically exposed to both internal and
      external radiation.

PMID- 12069311
TI  - Social interactions affect physiological consequences of sublethal copper
      exposure in rainbow trout, Oncorhynchus mykiss.
AB  - The interactions of sublethal waterborne copper exposure and social dominance
      behavior were examined in juvenile rainbow trout. Dominance hierarchies were
      determined between pairs of fish by behavioral observations and among groups of
      10 fish by the use of passive integrated transponder (PIT) tagging equipment. The
      present study is one of the first to utilize this novel PIT tag method for
      behavioral assessment. Feeding behavior was quantified by placing a PIT tag
      recorder at the entrance to the feeding area. Linear dominance hierarchies were
      documented based on these observations of feeding behavior. Dominance hierarchies
      established in control water were not altered by exposure to 30 microg/L of
      copper; however, physiological responses of fish to sublethal concentrations of
      copper were related to social rank. Subordinate fish exhibited a higher
      accumulation of copper in both gill and liver tissue. Subordinates of paired fish
      were also shown to have a higher uptake of sodium than dominant fish, and the
      uptake of sodium was correlated with uptake of copper from the water. Therefore,
      within a population of fish, it cannot be assumed that individuals of different
      social status will exhibit the same physiological responses to the presence of
      copper.

PMID- 12069312
TI  - Response of the amphibian tadpole Xenopus laevis to atrazine during sexual
      differentiation of the ovary.
AB  - Xenopus laevis tadpoles (stage 56) were exposed to 21 microg/L atrazine under
      laboratory-controlled conditions in a static system. Following a 48-h exposure
      period at 21+/-0.5 degrees C during sexual differentiation, tadpoles were fixed,
      and the kidney-gonad complex was microdissected. Quantitative histological
      analysis revealed in atrazine-exposed ovaries a significant (p < 0.05) increase
      in frequency of secondary oogonia. Atresia, or oogonial resorption of both
      primary and secondary oogonia, also increased significantly (p < 0.05). The
      results suggest that these primary germ cells, which constitute the total number
      of germ cells in the ovary for the reproductive life of the organism, were
      reduced by 20% following a 48-h exposure period compared to 2% in controls.

PMID- 12069313
TI  - Relationship between lysosomal membrane destabilization and chemical body burden
      in eastern oysters (Crassostrea virginica) from Galveston Bay, Texas, USA.
AB  - Lysosomal destabilization was measured by using hemocytes of eastern oysters
      (Crassostrea virginica) collected along a chemical concentration gradient in
      Galveston Bay, Texas, USA. Results of the lysosomal response were compared to
      concentrations of organic compounds and trace elements in oyster tissue.
      Concentrations (on a dry-wt basis) ranged from 288 to 2,390 ng/g for polycyclic
      aromatic hydrocarbons (PAHs), 38 to 877 ng Sn/g for tri-n-butyltin (TBT), 60 to
      562 ng/g for polyclorinated biphenyls (PCBs), and 7 to 71 ng/g for total DDT.
      Trace element concentrations (on a dry-wt basis) ranged from 1.1 to 4.0 microg/g
      for Cd, 105 to 229 microg/g for Cu, 212 to 868 microg/g for Al, and 1,200 to
      8,180 microg/g for Zn. The percentage of destabilized lysosomes ranged from 34 to
      81%. A significant positive correlation (p < 0.05) was observed between lysosomal
      destabilization and body burden of organic compounds (PAHs, PCBs, TBT, and
      chlorinated pesticides). No significant correlation was found between metal
      concentrations and lysosomal destabilization. Based on lysosomal destabilization,
      the study sites in Galveston Bay can be placed in one of three groups: healthy
      (Hanna Reef and Confederate Bay), moderately damaged (Offats Bayou and Todd's
      Dump), and highly damaged (Yacht Club and Ship Channel). Lysosomal
      destabilization that is consistent with toxic chemical body burdens supports
      previous observations that lysosomal membranes are damaged by toxic chemicals and
      indicates that this method can serve as an early screening tool to assess overall
      ecosystem health by using oysters.

PMID- 12069314
TI  - Bauxite manufacturing residues from Gardanne (France) and Portovesme (Italy)
      exert different patterns of pollution and toxicity to sea urchin embryos.
AB  - This study was designed to investigate the composition and toxicity of solid
      residues from bauxite manufacturing plants. Soil and dust samples were collected
      in the proximity of two bauxite plants (Gardanne, France, and Portovesme, Italy).
      Samples were analyzed for their content of some selected inorganic contaminants
      by means of inductively coupled plasma optical emission spectroscopy (ICP-OES)
      either following acid digestion procedures or by seawater release of soluble
      components. Toxicity was tested by sea urchin bioassays to evaluate a set of
      toxicity endpoints including acute embryotoxicity, developmental defects, changes
      in sperm fertilization success, transmissible damage from sperm to the offspring,
      and cytogenetic abnormalities. Inorganic analysis showed two distinct sets of
      inorganic contaminants in Gardanne versus Portovesme, including Al, Cr, Cu, Fe,
      Mn, Pb, Ti, and Zn; sample composition (seawater-soluble contaminants) and
      toxicity showed a noteworthy association. The most severe toxicity to
      embryogenesis and to sperm fertilization success was exerted by some Portovesme
      samples (0.03-0.5% w/v), with a significant association between toxicity and dose
      related seawater release of Zn, Pb, and Mn. Seawater extraction of a toxic dust
      sample (G20) from the Gardanne factory showed increasing seawater release of Al,
      Fe, and Mn; the G20 sample, at the level of 0.5%, affected both developing sea
      urchin embryos and sperm (offspring quality). Soil samples around the Gardanne
      factory showed the highest frequency of toxic soil sites eastward from the
      factory. The present data point to solid deposition from bauxite plants as a
      potential subject of environmental health concern. The results suggest that
      extraction methods for evaluating the toxicity of complex mixtures should be
      based on the environmental availability of mixture components. The differences in
      sample toxicity among the tested sites, however, suggest possible site-to-site
      variability in geochemical and/or technological parameters.

PMID- 12069315
TI  - Biological properties of arginine-based gemini cationic surfactants.
AB  - Biological properties of novel gemini (double-chain/double-head) cationic
      surfactants, Nalpha,Nomega-bis(Nalpha-acylarginine)alpha,omega-alkylendiamides,
      so-called bis(Args), are reported. The effect of both the alkyl (10 and 12 carbon
      atoms) and the spacer chain (from 2-10 methylene groups) of bis(Args) on their
      antimicrobial activity, acute toxicity on Daphnia magna and Photobacterium
      phosphoreum, and aerobic biodegradability is studied. These surfactants
      constitute a novel class of chemicals of low toxicity with excellent surface
      properties and considerable antimicrobial activity. The aquatic toxicity of these
      compounds is lower than that of the conventional Monoquats. As regards the
      biodegradation test, the molecules with a spacer chain < or =6 methylene groups
      can be considered as ready biodegradable. The increase of hydrophobicity in the
      bis(Args) is a negative structural parameter for their environmental behavior.

PMID- 12069316
TI  - Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I)
      to Daphnia magna. Part 1: description of the chemical system.
AB  - Experiments were designed to assess the potential protective effect of the
      presence of sulfide against the acute (48-h) toxicity of silver(I) to Daphnia
      magna. Tests were conducted in borosilicate glass beakers (250 ml) in moderately
      hard synthetic water. Toxicity solutions were replaced after 24 h by static
      renewal method. This paper describes the chemical system, and the acute toxicity
      results are presented in a companion paper. Sulfide was below detection limit (<5
      nM) in controls with no sulfide added. Sulfide, added as zinc sulfide clusters at
      approximately 35- or approximately 350-nM concentration, dropped in concentration
      to approximately 25 and 250 nM, respectively, over the 24-h period of
      measurements. Silver also decreased in concentration during the experiment (up to
      59%), and the rate of loss was greater in the absence of sulfide compared with
      the presence of sulfide. A filtration experiment indicated a 1:1 binding ratio of
      silver to sulfide and a conditional stability constant for the Ag(I)-zinc sulfide
      complex of log K' = 8.9. The losses of sulfide and silver during the experiments
      highlighted the need for regular monitoring of the important chemical components
      of the system, even during short (48-h) toxicity tests.

PMID- 12069317
TI  - Evaluation of the effect of reactive sulfide on the acute toxicity of silver (I)
      to Daphnia magna. Part 2: toxicity results.
AB  - The protective effect of reactive sulfide against AgNO3 toxicity to Daphnia magna
      neonates was studied. Acute (48-h) toxicity tests were performed in the absence
      (<5 nM) and presence of low (approximately 25 nM) and high (approximately 250 nM)
      concentrations of zinc sulfide clusters under oxic conditions. In both the
      presence and the absence of sulfide, lower mean lethal concentration (LC50)
      values were observed when measured as opposed to nominal silver concentrations
      were used in calculations. This reflected the fact that measured total silver
      concentrations were lower than nominal concentrations due to losses of silver
      from solution observed during the experiment. High concentration (approximately
      250 nM) of sulfide completely protected against toxicity up to the highest silver
      concentration tested (2 microg/L [19 nM]) with measured silver data. In the
      presence of environmentally realistic levels of sulfide (approximately 25 nM) in
      receiving waters, acute silver toxicity was reduced by about 5.5-fold. However,
      when filtered (0.45 microm) silver concentrations alone were considered, toxicity
      (48-h LC50) was similar in the absence (0.22 microg/L) and presence (0.28
      microg/L) of sulfide. The difference between measured total and filtered silver
      was attributed to chemisorption of the metal sulfide onto the membrane filter and
      provides evidence that the toxic fraction of silver is that which is unbound to
      sulfide. Accumulation of silver was greater in daphnids exposed to silver in the
      presence of sulfide than in its absence, even though a toxic effect was not
      observed under these conditions. In this case, silver appears to be incorporated
      by daphnids rather than merely adsorbed on the surface. Our results point out the
      need to incorporate sulfide into the acute biotic ligand model and to assess its
      potentially large role in preventing chronic toxicity.

PMID- 12069318
TI  - A framework for prioritizing fragrance materials for aquatic risk assessment.
AB  - More than 2,100 chemically defined organic chemicals are listed in the Research
      Institute of Fragrance Materials/Flavor and Extract Manufacturers' Association
      (RIFM/FEMA) Database that are used as ingredients of fragrances for consumer
      products. An approach was developed for prioritizing these fragrance materials
      for aquatic risk assessment by first estimating the predicted environmental
      concentration (PEC) of these fragrance materials in the aquatic environment based
      upon their physicochemical properties and annual volume of use. Subsequently, an
      effect level was predicted with a general quantitative structure-activity
      relationship (QSAR) for aquatic toxicity, and a predicted no-effect concentration
      (PNEC) was calculated from this effect level by using an assessment factor (AF)
      that accounts for uncertainty in the toxicity QSAR prediction. A conservative AF
      of 10(6) was applied to the endpoint predicted by the QSAR to provide an adequate
      margin of safety in the calculation of the PNEC. The PEC was compared to the PNEC
      to characterize the risk to freshwater aquatic organisms (e.g., Daphnia magna and
      Pimephales promelas). If the ratio of PEC to PNEC was below one, the material was
      considered to have negligible environmental risk and to be acceptable for the
      aquatic environment at current use levels. If this ratio exceeded one, the PNEC
      was refined by using more specific QSAR models (Ecological Structure-Activity
      Relationships [ECOSAR]). If the ratio continued to exceed one, the material
      became a candidate for further aquatic risk assessment procedures, which involve
      iterative steps to refine the PEC, the PNEC, or both by using measured
      ecotoxicological endpoints. Prioritization for this latter process can be based
      upon the magnitudes of the estimated PEC:PNEC ratios. When using the first tier
      of this approach, only 568 of 2,141 fragrance materials (26.5%) in the RIFM/FEMA
      Database had PEC:PNEC ratios greater than one. This percentage decreased to only
      164 materials (7.7%) when PNECs were derived with ECOSAR. Comparison of predicted
      PECs and PNECs with those based upon measured data confirmed the conservatism and
      low risk for type I errors associated with the framework. These combined
      exercises demonstrated the ability of this highly precautionary risk-based
      screening approach to quickly prioritize a large number of materials without
      benefit of experimental ecotoxicological or fate data.

PMID- 12069319
TI  - Predicting acute zinc toxicity for Daphnia magna as a function of key water
      chemistry characteristics: development and validation of a biotic ligand model.
AB  - The individual effect of different major cations (Ca2+, Mg2+, Na+, K+, and H+) on
      the acute toxicity of zinc to the waterflea Daphnia magna was investigated. The
      48-h median effective concentration (EC50) in the baseline test medium (i.e., a
      standard medium with very low ion concentrations) was about 6 microM (Zn2+). An
      increase of Ca2+ (from 0.25 mM to 3 mM), Mg2+ (from 0.25 mM to 2 mM), and Na+
      activity (from 0.077 mM to 13 mM) reduced zinc toxicity by a factor of 6.3, 2.1,
      and 3.1, respectively. No further toxicity reduction was observed when Ca2+ and
      Mg2+ activities exceeded 3.0 and 2.0 mM, respectively. Both K+ and H+ did not
      significantly alter zinc toxicity (expressed as Zn2+ activity). From these data,
      conditional stability constants for Ca2+ (log K = 3.24), Mg2+ (log K = 2.97), Na+
      (log K = 2.16), and Zn2+ (log K = 5.31) were derived and incorporated into a
      biotic ligand model (BLM) predicting acute zinc toxicity to D. magna in surface
      waters with different water quality characteristics. Validation of the developed
      BLM using 17 media with different pH, hardness, and dissolved organic carbon
      (DOC) content resulted in a significant correlation coefficient (R2 = 0.76)
      between predicted and observed 48-h EC50. Eighty-eight percent of the predictions
      were within a factor of 1.3 of the observed 48-h EC50.

PMID- 12069320
TI  - Integrated biomarker response: a useful tool for ecological risk assessment.
AB  - A battery of biomarkers is often used to evaluate the effects of exposure to
      chemical contaminants and detect responses to environmental stress.
      Unfortunately, field application of biomarkers is subject to various constraints
      (e.g., the availability of living material) that can limit data acquisition and
      prevent the use of multivariate methods during statistical analysis. In these
      circumstances, a simple method is needed to summarize biomarker responses and
      simplify their interpretation in biomonitoring programs. The present study used
      star plots to display results for the panel of biomarkers used for each station
      and survey. Integrated biomarker response (IBR) was then computed as the star
      plot area. Star plots using IBR values instead of biomarker data make it possible
      to visualize between-site and/or between-survey differences for comparison with
      exposure conditions. This approach was applied to sites in the Baltic Sea and the
      Seine Estuary, English Channel. In both cases, IBR values were visually compared
      to polycyclic aromatic hydrocarbons (PAH) or polychlorobiphenyls (PCB) levels
      measured in mussel or fish tissues. The IBR, as an indicator of environmental
      stress, appears to be a useful tool for scientists and managers in assessing
      ecological risk.

PMID- 12069321
TI  - Preparation of alginate/galactosylated chitosan scaffold for hepatocyte
      attachment.
AB  - Galactose-carrying lactobionic acid was covalently coupled with chitosan for
      determining hepatocyte specificity. Galactosylated chitosan (GC) was reacted with
      Ca-alginate (ALG) gel through the electrostatic interaction of carboxylic groups
      of alginate with amine groups of GC. Highly porous, three-dimensional sponge
      composed of ALG and GC was prepared to provide specific hepatocyte recognition
      signals and enhance the mechanical property of the ALG sponge. Observation of the
      sponge through scanning electron microscopy revealed that sponge was a highly
      porous microstructure with interconnected pores. Porosity and pore size of the
      sponge were greatly dependent on the content and molecular weight of GC, and
      freezing temperature. The mechanical property of the ALG/GC sponge was enhanced
      with an increase of the GC content. Spheroid formation and viability of
      hepatocytes of the ALG/GC sponge were higher than those of the ALG one.

PMID- 12069322
TI  - Bacterial adhesion to titanium-oxy-nitride (TiNOX) coatings with different
      resistivities: a novel approach for the development of biomaterials.
AB  - In this study the quantitative adhesion of a strain of Staphylococcus
      epidermidis, Streptococcus mutans and Pseudomonas aeruginosa to and the ease of
      removal from different TiNOX coatings was investigated by means of a parallel
      plate flow chamber and in situ image analysis. Quality of adhesion was determined
      by counting bacteria which remained attached to the surface after exposure to an
      air-liquid interface. S. epidermidis and S. mutans showed a bipolar adhesion
      pattern with highest numbers of adhesion at low and high resistivity with lowest
      adhesions at a resistivity of 10(4) microohms cm. P. aeruginosa was the least
      adherent organism. These results indicate that the affinity of these three
      strains under the current experimental conditions is minimal for TiNOX coatings
      with a specific resistivity. TiNOX coatings with pre-adsorbed fibrinogen showed
      different numbers of S. epidermidis adhered to the different coatings. However,
      the affinity of this strain for fibrinogen-coated TiNOX remains low when the
      resistivity is around 10(4) microohms cm. This indicates that the specific
      influence of the resistivities of the TiNOX coatings is transferred through the
      adsorbed fibrinogen film to the interface with adhering bacteria.

PMID- 12069323
TI  - Study on the stabilisation of collagen with vegetable tannins in the presence of
      acrylic polymer.
AB  - Collagen, a unique connective tissue protein finds extensive application as
      biocompatible biomaterial in wound healing, as drug carriers, cosmetics, etc. A
      study has been undertaken to stabilise Type-I collagen of rat-tail tendon using
      plant polyphenol (Acacia Mollissima) in the presence of an acrylic polymer. It
      has been found that collagen fibres pre-treated with acrylic polymer followed by
      the treatment with Acacia Mollissima exhibited an increase in hydrothermal
      stability by 25 degrees C. Infrared spectroscopic studies display the changes in
      the spectral characteristics of native and treated collagen films. Transmission
      electron microscopic and circular dichroic studies provide an insight into the
      understanding of the improved stabilisation of collagen, due to treatment with
      acrylic polymer and plant polyphenols. The study is expected to enhance the
      biomaterial applications of collagen tissues.

PMID- 12069324
TI  - Lysineurethanedimethacrylate--a novel generation of amino acid based monomers for
      bone cements and tissue repair.
AB  - A novel amino acid based dimethacrylate monomer (lysineurethanedimethacrylate,
      LUDM) was prepared by the addition of hydroxyethylmethacrylate (HEMA) to
      lysinediisocyanate (LDI). The structure was confirmed by FT-IR and 1H and 13C NMR
      spectroscopy as well as FAB-MS. Photopolymerized LUDM exhibited low volume
      shrinkage upon polymerization, good mechanical properties (Young's modulus: 3740
      MPa) and high thermal stability. Osteoblast adhesion and growth on polymerized
      LUDM samples evidenced the biocompatibility. Further improvement of the
      mechanical properties was obtained by using Ca-hydroxyapatite as inorganic filler
      varying between 10 and 30 wt%. The Young's and flexural moduli increased with
      increasing filler content ranging from 3740 to 5250 MPa and from 2020 to 3690
      MPa, respectively. The mechanical properties and the good biocompatibility of the
      lysine-based methacrylate networks make them interesting materials for medical
      applications, e.g. bone cements, and tissue engineering.

PMID- 12069325
TI  - Impact of sterilization on the porous design and cell behavior in collagen
      sponges prepared for tissue engineering.
AB  - This study investigates the impact of different sterilization processes on
      structural integrity and stability of collagen sponges designed for tissue
      engineering. Collagen sponges with uniform pore size (20 microm) were sterilized
      either with ethylene oxide (EO) or gamma irradiation (2.5 Mrad). Gamma-sterilized
      sponges showed a dramatic decrease of resistance against enzyme degradation and
      severe shrinkage after cell seeding. Collapsed porosity inhibited fibroblasts and
      barred completely the human umbilical vein endothelial cell ingrowth into the
      sponges. On the contrary, the porous structure and stability of EO-sterilized
      sponges remained almost unaltered. Fibroblasts and endothelial cells exhibited
      favorable proliferation and migration within sponges with normal morphology.
      Tubular formation by seeded endothelial cells occurred early in the first week.
      Therefore, we emphasize that the impact of sterilization of biomaterials is
      substantial and any new procedure has to be evaluated by correlating the impact
      of the procedure on the porous structure with cell proliferation behavior.

PMID- 12069327
TI  - On the interaction of polyacrylic acid as a conditioning agent with bovine
      enamel.
AB  - In the present paper, the effects of polyacrylic acid (PAA) conditioning on the
      morphology and chemistry of bovine enamel surface and the resulting interfacial
      reactions are being investigated using photometric, microscopic (SEM, AFM),
      electron spectroscopic (XPS) and staining methods (neutral red dye). The results
      are compared to two reference surfaces obtained by simple grinding and by etching
      with a phosphoric acid solution. It is shown that PAA conditioning leads to the
      leaching of calcium and phosphorus ions, to the smoothening of the surface and
      probably to the formation of a polymeric film at the surface. A mechanism by
      which a preliminary PAA conditioning of the enamel leads to the reported higher
      bonding strength between enamel and glass ionomer cements is proposed.

PMID- 12069326
TI  - Evaluation of the TiMo12Zr6Fe2 alloy for orthopaedic implants: in vitro
      biocompatibility study by using primary human fibroblasts and osteoblasts.
AB  - To reveal the biocompatibility of TiMo12Zr6Fe2 (TMZF), a new titanium alloy used
      since 1998 for orthopaedic prosthesis, we compared the behavior of primary human
      fibroblasts and osteoblasts grown on TMZF discs or on plastic tissue culture
      dishes, a widely used material specifically treated by the manufacturer to
      enhance cell growth. Proliferation, differentiation. RNA and collagen type I
      expression level of human cells were carried out. The analysis were performed
      over a period of 96 h. Fibroblasts behaved at the same way on the two different
      supports after 48 h, their number increased after 96 h when cells were grown on
      the alloy. Osteoblasts adhered and proliferated on the alloy discs as well as on
      plastic. RNA expression level was not affected. Interestingly, cell number at
      each time point was higher for fibroblasts than for osteoblasts. The RNA
      expression level was higher for the osteoblasts. Both cell types cultured on the
      alloy revealed an increase in the amount of type I collagen and a similar
      electrophoretic pattern was found for collagen produced by fibroblasts and
      osteoblasts grown on either supports. These results indicate good
      biocompatibility of the TMZF alloy, which allowed adhesion and proliferation of
      both the examined cell types and suggest that TMZF is a promising material for
      orthopaedic implants.

PMID- 12069328
TI  - Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium
      implants.
AB  - Thin calcium phosphate (Ca-P) coatings have been introduced to overcome the
      shortcomings of plasma-sprayed Ca-P coatings. In our previous experiments, thin
      Ca-P coatings also enabled the immobilization of bisphosphonate, which is a drug
      used to treat osteoporosis. The present study was designed to evaluate the bone
      response to titanium implants treated with a thin Ca-P coating and
      bisphosphonate. Forty cylindrical commercially pure titanium implants with a
      length of 7 mm and a diameter of 3 mm were used as test implant fixtures. Three
      groups of surface-treated implants were prepared: (1) blasted with titanium
      powder and etched with a solution of 10% HF + 5% HNO3 (control); (2) modified
      with 0.5-microm thick Ca-P coatings and rapid heat-treating, and (3) immobilized
      with bisphosphonate by immersion in pamidronate disodium solution (10(-2) M) for
      24 h at 37 degrees C. These surface-treated implants were inserted into
      edentulous areas in the mandibular molar region of five beagle dogs. After
      implantation periods of 4 and 12 weeks, the bone implant interface was evaluated
      histologically and histomorphometrically. All measurements were statistically
      evaluated using a one-way ANOVA and Fisher PLSD test for multiple comparisons
      among the means. Four weeks after the implantation, higher percentage of bone
      contact was found around the thin Ca-P-coated implants compared to that of the
      control group. The highest percentage of bone contact was found around the
      bisphosphonate-immobilized implants after 12 weeks of implantation. These data
      suggest that a thin coating of calcium phosphate followed by bisphosphonate
      immobilization is effective in the promotion of osteogenesis on surfaces of
      dental implants.

PMID- 12069329
TI  - On the properties of two binary NiTi shape memory alloys. Effects of surface
      finish on the corrosion behaviour and in vitro biocompatibility.
AB  - The present paper compares the transformation behaviour and mechanical properties
      of two orthodontic wires of close chemical compositions. The effects of surface
      topography and surface finish residues on the potentiodynamic corrosion behaviour
      and biocompatibility are also reported. The cytotoxicity tests were performed on
      both alloys in fibroblast cell cultures from human gingiva using the MTT test. It
      is shown that the surface finish and the amounts of surface finish residues
      affect dramatically the corrosion resistance. Bad surface finish results in lower
      corrosion resistance. The in vitro biocompatibility, though not affected to the
      extent of corrosion resistance, is also reduced as the surface roughness and the
      amounts of residues increase. This is thought to be due to surface effects on
      corrosion and metallic ions release.

PMID- 12069330
TI  - In vivo bone tissue response to a canasite glass-ceramic.
AB  - The aim of this study was to determine the biocompatibility and osteoconductive
      potential of a high-strength canasite glass ceramic. Glass-ceramic rods were
      produced using the lost-wax casting technique and implanted in the mid-shafts
      rabbit femurs. Implants were harvested at 4, 13 and 22 weeks and prepared for
      light and electron microscopy. Hydroxyapatite was used as a control material.
      Hydroxyapatite implants were surrounded by new mineralised bone tissue after 4
      weeks of implantation. The amount of bone surrounding the implant increased
      slightly at 13 weeks. In contrast, canasite glass and glass ceramic implants were
      almost entirely surrounded by soft tissue during all the time periods. Close
      contact between bone and canasite glass-ceramic implant without the intervening
      fibrous tissue was observed in only a few regions. The canasite formulation
      evaluated was not osteoconductive and appeared to degrade in the biological
      environment. It was therefore concluded that the canasite formulation used was
      unsuitable for use as implant. Further work is required to improve the
      biocompatibility of these materials with bone tissue. It is possible that this
      could be achieved by reducing the solubility of the glass and glass ceramic.

PMID- 12069331
TI  - Evaluation of the antiadhesion potential of UV cross-linked gelatin films in a
      rat abdominal model.
AB  - Among five kinds of rat adhesion models tested, the following model was selected.
      The epigastric vein 2.5 cm from the midline of the abdomen was cut by sharp
      scissors, and the lateral side of the cut epigastric vein was ligated using a 3-0
      silk suture. This model could be easily prepared and gave a rate of adhesion
      formation of 90%, which was useful for screening antiadhesive materials. For the
      kinetic study of tissue adhesion in this model, an injured site was covered with
      a non-degradable poly(vinyl alcohol) (PVA) film. The incidence rate of adhesion
      was 18%, when the PVA film covered the injured site for 2 days. This suggests
      that an antiadhesive barrier should cover the injured site for at least 2 days.
      The antiadhesion efficacy of cross-linked gelatin films were evaluated using this
      adhesion model. The UV cross-linked gelatin film which was designed to exist for
      2 days but to disappear at day 3 in the rat abdominal cavity showed the highest
      antiadhesion efficacy.

PMID- 12069332
TI  - In vitro bioactivity of a biocomposite fabricated from HA and Ti powders by
      powder metallurgy method.
AB  - Traditionally, hydroxyapatite was used as a coating material on titanium
      substrate by various techniques. In the present work, a biocomposite was
      successfully fabricated from hydroxyapatite and titanium powders by powder
      metallurgy method. Bioactivity of the composite in a simulated body fluid (SBF)
      was investigated. Main crystal phases of the as-fabricated composite are found to
      be Ti2O, CaTiO3, CaO, alpha-Ti and a TiP-like phase. When the composite is
      immersed in the simulated body fluid for a certain time, a poor-crystallized,
      calcium-deficient, carbonate-containing apatite film will form on the surface of
      the composite. The time required to induce apatite nucleation is within 2 h. In
      addition, the apatite is also incorporated with a little magnesium and chlorine
      element. It is found that Ti2O has the ability to induce the formation of bone
      like apatite in the SBF. And a dissolve of the CaO phase could also provide
      favorable conditions for the apatite formation, by forming open pores on the
      surface of the composite and increasing the degree of supersaturation of the SBF
      with respect to the apatite.

PMID- 12069334
TI  - Microstructures and mechanical properties of powder injection molded Ti-6Al-4V/HA
      powder.
AB  - Taguchi method with an L9 orthogonal array was employed to investigate the
      sintered properties of Ti-6Al-4V/HA tensile bars produced by powder injection
      molding. The effects of sintering factors at the 90% significance level:
      sintering temperature (1050 degrees C, 1100 degrees C and 1150 degrees C),
      heating rate (5 degrees C/min, 7.5 degrees C/min and 10 degrees C/min), holding
      time (30, 45 and 60 min) and cooling rate (5 degrees C/min, 20 degrees C/min and
      40 degrees C/min) were investigated. Results showed that sintering temperature,
      heating rate and cooling rate have significant effects on sintered properties,
      whereas the influence of holding time was insignificant. It was found that a
      sintering temperature of 1100 degrees C, a heating rate of 7.5 degrees C/min and
      a cooling rate of 5 degrees C/min increased the relative density, Vicker's
      microhardness, flexural strength and flexural modulus. However, a further
      increment of sintering temperature to 1150 degrees C did not show any discernable
      improvement in the relative density and Vicker's microhardness, but there was a
      slight increase of 0.6% and 0.9% in the flexural strength and flexural modulus,
      respectively. Mechanically strong Ti-6Al-4V/HA parts with an open porosity of
      around 50% were developed.

PMID- 12069333
TI  - Effect of surface chemistries and characteristics of Ti6Al4V on the Ca and P
      adsorption and ion dissolution in Hank's ethylene diamine tetra-acetic acid
      solution.
AB  - This study examined the influence of chemistries and surface characteristics of
      Ti6Al4V on the adsorption of Ca and P species and ion dissolution behavior of the
      material exposed in Hank's solution with 8.0 mM ethylene diamine tetra-acetic
      acid at 37 degrees C. The variation of chemistries of the alloy and nano-surface
      characteristics (chemistries of nano-surface oxides, amphoteric OH group adsorbed
      on oxides, and oxide thickness) was effected by surface modification and three
      passivation methods (34% nitric acid passivation. 400 degrees C heated in air,
      and aged in 100 degrees C water). X-ray photoelectron spectroscopy and Auger
      electron spectroscopy were used for surface analyses. The chemistries of nano
      surface oxides in a range studied should not change the capability of Ca and P
      adsorption. Nor is the capability affected significantly by amphoteric OH group
      and oxide thickness. However, passivations influence the surface oxide thickness
      and the early stage ion dissolution rate of the alloy. The rate-limiting step of
      the rate can be best explained by metal-ion transport through the oxide film,
      rather than hydrolysis of the film. Variation of the chemistries of titanium
      alloy alters the electromotive force potential of the metal, thereby affecting
      the corrosion and ion dissolution rate.

PMID- 12069335
TI  - Soft tissue findings above submerged titanium implants--a histological and
      spectroscopic study.
AB  - The aim of this study was to check the titanium level within the muco-periosteal
      flaps covering submerged titanium implants. The investigated material included 38
      biopsies taken after 2.4-18 months (mean: 5.9) after implant insertion. Due to
      the evident time delay between implantation and taking the biopsy any influence
      of the implantation trauma itself was excluded. The implants came from the
      following producers: HaTi (Matthys, Switzerland), ITI (Straumann, Switzerland)
      and Branemark (Nobelbiocare. Sweden). The surface areas of these implants differ
      in size and structure. A comparison between the titanium impregnation of the
      investigated biopsies did not demonstrate any remarkable influence of the surface
      differences. This can be explained by the fact that only the top diameter and not
      the implant surface as a whole was the contact area with the excised tissue.
      Titanium in the biopsies was analysed in terms of its effect histologically and
      regarding the titanium quantity by spectrophotometry. Even the highest titanium
      contamination was without a negative effect on the muco-periosteal cover flaps. A
      correlation between time delay between implantation and biopsy or of the titanium
      amount and tissue reactions was not demonstrable. In summary, the results again
      highlighted the biological acceptance of titanium.

PMID- 12069336
TI  - In vitro reaction of endothelial cells to polymer demixed nanotopography.
AB  - The introduction of topography to material surfaces has been shown to strongly
      affect cell behaviour, and the effects of micrometric surface morphologies have
      been extensively characterised. Research is now starting to investigate the
      reaction of cells to nanometric topography. This study used polymer demixing of
      polystyrene and poly(4-bromostyrene) producing nanometrically high islands, and
      observed endothelial cell response to the islands. Three island heights were
      investigated; these were 13, 35 and 95 nm. The cells were seen to be more spread
      on the manufactured topographies than that on flat surfaces of similar chemistry.
      Other morphological differences were also noted by histology, fluorescence and
      scanning electron microscopy, with many arcuate cells noted on the test surfaces,
      and cytoskeletal alignment along the arcuate features. Of the nanotopographies,
      the 13 nm islands were seen to give the largest response, with highly spread cell
      morphologies containing well-defined cytoskeleton.

PMID- 12069337
TI  - High power light emitting diode (LED) arrays versus halogen light polymerization
      of oral biomaterials: Barcol hardness, compressive strength and radiometric
      properties.
AB  - The clinical performance of light polymerized dental composites is greatly
      influenced by the quality of the light curing unit (LCU) used. Commonly used
      halogen LCUs have some specific drawbacks such as decreasing light output with
      time. This may result in a low degree of monomer conversion of the composites
      with negative clinical implications. Previous studies have shown that blue light
      emitting diode (LED) LCUs have the potential to polymerize dental composites
      without having the drawbacks of halogen LCUs. Since these studies were carried
      out LED technology has advanced significantly and commercial LED LCUs are now
      becoming available. This study investigates the Barcol hardness as a function of
      depth, and the compressive strength of dental composites that had been
      polymerized for 40 or 20s with two high power LED LCU prototypes, a commercial
      LED LCU, and a commercial halogen LCU. In addition the radiometric properties of
      the LCUs were characterized. The two high power prototype LED LCUs and the
      halogen LCU showed a satisfactory and similar hardness-depth performance whereas
      the hardness of the materials polymerized with the commercial LED LCU rapidly
      decreased with sample depth and reduced polymerization time (20 s). There were
      statistically significant differences in the overall compressive strengths of
      composites polymerized with different LCUs at the 95% significance level (p =
      0.0016) with the two high power LED LCU prototypes and the halogen LCU forming a
      statistically homogenous group. In conclusion, LED LCU polymerization technology
      can reach the performance level of halogen LCUs. One of the first commercial LED
      LCUs however lacked the power reserves of the high power LED LCU prototypes.

PMID- 12069338
TI  - Morphological regulation and crystal growth of hydrothermal-electrochemically
      deposited apatite.
AB  - Apatite was deposited on commercially pure titanium plates using a hydrothermal
      electrochemical method in an electrolyte containing calcium and phosphate ions.
      Needle-like apatites were synthesized in 43 kinds of condition with different
      electrolyte temperatures (90-200 degrees C), current densities (5.0-25.0 mA/cm2),
      and current loading times (10-120 min). The length of one side of the hexagonal
      apatite and longitudinal length of them were determined through field-emission
      type scanning electron microscopic photographs. The size of needle-like apatites
      remarkably increased with the electrolyte temperature and current loading time,
      and slightly changed with current density. Multivariate analysis revealed that
      both size and shape of apatite needle on titanium substrate can be regulated
      accurately by systematic control of the electrolyte temperature, current density,
      and current loading time. These results revealed that hydrothermal
      electrochemical deposition of apatite consists of two processes: nucleation and
      crystal growth, which strongly depend on the electrolyte temperature and current
      density.

PMID- 12069339
TI  - Biocompatibility studies of new multiblock poly(ester-ester)s composed of
      poly(butylene terephthalate) and dimerized fatty acid.
AB  - This study was undertaken to evaluate the biocompatibility of new multiblock
      poly(ester-ester)s proposed as an alternative to Hunter silastic prosthesis used
      in a two-stage tendon reconstruction. Methanol-extracted polymeric material
      retained its weight, demonstrating the absence of leachable particles (e.g. low
      molecular weight oligomers). Implantation tests indicated that the observed
      tissue changes were similar to those obtained with silicone, no evidence of
      contact necrosis being observed. The unchanged morphology of rat liver
      hepatocytes and the lack of parenchymal necrosis also indicated that exposure to
      the investigated polymers did not cause any cytotoxic reactions.

PMID- 12069340
TI  - Physical and chemical processing for a human dura mater substitute.
AB  - OBJECT: Allogenic human fascia lata used in neurosurgery, as dura mater
      substitute, can be associated with a risk of viral and bacterial transmission.
      Chemical and physical procedures, developed to inactivate virus and bacteria,
      have been applied to fascia lata. The aim of this study consists in the
      evaluation of the biological properties of this treated graft. METHODS: Grafts
      were treated with solvent detergents, freeze-dried for conservation and gamma
      irradiated (25,000 Gy) for sterilization. The indirect toxicity evaluation was
      performed by extraction method, according to the International Standard
      Organization (ISO). First, the cytotoxic effect of each extracts incubated in the
      presence of human fibroblasts (WI38) was quantitatively assessed by measuring the
      cell growth, the viability (succinate dehydrogenase activity, MTT), the membrane
      integrity (uptake of the neutral red by viable cells, NR) as well as the release
      of lactate dehydrogenase in the culture medium. Second, confocal laser scanning
      microscopy (CLSM) was used to assess the direct contact between human primary
      fibroblasts and graft. CLSM was performed at days 3 and 7 after cells loading.
      RESULTS: No acute cytotoxicity was observed for chemically processed allografts.
      Cells loaded on the graft have demonstrated a good growth and spreading.
      CONCLUSIONS: Human fascia lata secured against conventional and non-conventional
      agents is a fully biocompatible alternative to the available dural graft
      materials.

PMID- 12069341
TI  - Colonization of ion-modified polyethylene with vascular smooth muscle cells in
      vitro.
AB  - Polyethylene (PE) foils were implanted with 40 and 150 keV Ar+ ions to the
      fluences from 1 x 10(13) to 1 x 10(15) cm(-2). Production of conjugated double
      bonds, characterizing degradation of the PE surface layer, was studied using UV
      VIS spectroscopy. Wettability of the PE surface, determined by conventional
      goniometric techniques, was shown to be an increasing function of both ion energy
      and fluence. It was also increased after exposure of PE to serum-supplemented
      cell culture media. Cell culture experiments showed that the ion irradiation
      significantly increased the adherence of vascular smooth muscle cells (VSMC) and
      their subsequent growth on the PE surface. On day 1 after seeding, the number of
      initially adhered VSMC exhibited two maxima. On day 3 after seeding. these maxima
      disappeared, which was partially due to a significantly shorter doubling time of
      VSMC. On the other ion-modified samples. the doubling time did not differ
      significantly from that on the unmodified PE. Enzyme-linked immunosorbent assay
      revealed increased concentration of talin, a protein of focal adhesion plaques,
      and alpha-actin, a marker of VSMC differentiation, in cells on ion-implanted
      surfaces. It can be concluded that the ion irradiation supports the adhesion and
      differentiation of VSMC without excessive proliferation of these cells.

PMID- 12069342
TI  - Nitinol versus stainless steel stents: acute thrombogenicity study in an ex vivo
      porcine model.
AB  - Acute and subacute stents thrombosis along with thrombus mediating neointimal
      proliferation within the stent struts remain major concerns in coronary stenting.
      Up to date, there is an obvious lack of data on the thrombogenicity of stent
      materials in physiological conditions. This study was performed to compare the
      relative thrombogenicity of nitinol versus stainless steel stents. Nitinol stents
      were laser cut to reproduce the exact geometry of the stainless steel Palmaz
      stents and tested in an ex vivo AV shunt porcine model under controlled
      conditions. Nitinol stents presented only small amounts of white and/or red
      thrombus principally located at the strut intersections while Palmaz stents
      clearly exhibited more thrombus. As a result, 125I-fibrin(ogen) adsorption and
      (111)I-platelets adhesion were significantly lower on nitinol than on stainless
      steel devices (36%, p = 0.03 for fibrin(ogen) and 63%, p = 0.01 for platelet).
      These results were confirmed by scanning electron observations showing different
      thrombus morphologies for nitinol and stainless steel. Along with the unique
      mechanical properties of nitinol, its promising haemocompatibility demonstrated
      in our study may promote their increasing use for both peripheral and coronary
      revascularization procedures.

PMID- 12069343
TI  - A study of tissue interface membranes from revision accord knee arthroplasty: the
      role of T lymphocytes.
AB  - Despite four decades of advances in the design of orthopaedic devices aseptic
      loosening remains a major cause for the revision of total joint arthroplasty.
      This study used the techniques of immunohistochemistry and reverse transcription
      polymerase chain reaction to identify the inflammatory cell types, cytokines and
      chemokines within the interface tissue surrounding failed Accord Knee prostheses.
      Many T cells were identified within the tissue: however, the classical marker of
      activation, CD25 was expressed on very few cells. Molecular analysis failed to
      detect the synthesis of either Th1 or Th2 cytokines. These results suggest that
      the T cells are being actively recruited to the site of inflammation along the
      chemokine gradients but are not participating in a classical immune response.

PMID- 12069344
TI  - Influence of charge density, sulfate group position and molecular mass on
      adsorption of chondroitin sulfate onto coral.
AB  - The adsorption of chondroitin sulfate onto granules of natural coral of specific
      diameter, between 100 and 500 microm, having high calcium content (> 98%) and a
      homogeneous surface was investigated. Several chondroitin sulfate samples
      desulfated to various extents, with a sulfate to disaccharide ratio (charge
      density) of 0.98-0.07 and non-sulfated polysaccharide possessing a chondroitin
      sulfate backbone structure were tested for their ability to adsorb onto coral.
      Adsorption of chondroitin sulfate onto coral depends on its charge density, as
      the removal of sulfate groups totally abolishes this capacity. Various
      chondroitin sulfates of molecular mass from 26,950 to 1140 were also tested. No
      appreciable effect depending on the molecular mass was evident. Also, chondroitin
      sulfate fractions with molecular mass of about 3530 (formed by about 6
      disaccharide units) and 1140 (formed by about 2 disaccharide units) retain their
      full capacity to adsorb onto coral. Furthermore, the position of sulfate groups
      inside the polysaccharide chains does not influence the ability of chondroitin
      sulfate to adsorb onto coral. In fact, chondroitin sulfate derivatives almost
      completely sulfated (> 90%) in position 4 of galactosamine and chondroitin almost
      completely (> 90%) sulfated in position 6 show a full adsorbtion onto coral.
      Thus, large amounts of chondroitin sulfate are adsorbed onto coral, and sulfate
      groups are of paramount importance in the adsorption process. On the other hand,
      the capacity of chondroitin sulfate to adsorb onto coral is quite aspecific. In
      fact, it does not depend on the presence of sulfate groups esterified in a
      specific position or sulfated sequences arranged in blocks but rather on the
      presence of sulfate groups, and this ability increases with increasing charge
      density, as indicated by the values of the Langmuir constant, the adsorption
      capacity, that decreases with decreasing chondroitin sulfate charge density
      reaching very low values for the totally desulfated polymer.

PMID- 12069345
TI  - Fibrin glue as an osteoinductive protein in a mouse model.
AB  - Fibrin sealant or fibrin glue (FG) has been found to be effective as a wound
      healing substance in surgery. However, its role in bone fracture healing and
      osseous tissue response is not fully understood. This ambiguity questions the
      potential of FG as an inductive protein. The present study was undertaken to
      evaluate the osteoinductive property of FG when coated with calcium phosphate and
      glass ceramics and implanted in the extraskeletal site of male Swiss albino mice.
      Implant materials used for this study were hydroxyapatite (HA) porous granules
      (300-350 microm), bioactive glass system (BGS)-AW type and calcium phosphate
      calcium silicate system (HABGS) non-porous granules (300-350 microm). Uncoated
      granules (control) and coated granules with 2.5 mg FG and 5 mg FG were implanted
      in the quadriceps muscle of mice and sacrificed after 28 days. Histologically,
      HA, BGS and HABGS implanted animal groups showed good healing response. However,
      neo-osteogenesis was observed only in the BGS and HABGS granules impregnated with
      FG. Furthermore, bone formation was observed to be more conspicuous in 5 mg FG
      coated BGS and HABGS granules when compared with 2.5 mg FG coated BGS and HABGS
      granules. Fluorochrome labeling proved that mineralization had already started by
      day 15 with FG preadsorbed BGS and HABGS granules. On the contrary, the uncoated
      granules did not show any de novo bone formation. This experimental study
      provides an evidence of the positive role of FG as a potential osteoinductive
      biologic tissue adhesive.

PMID- 12069346
TI  - Apatite-forming ability and mechanical properties of PTMO-modified CaO-SiO2
      hybrids prepared by sol-gel processing: effect of CaO and PTMO contents.
AB  - Transparent monolithics of triethoxysilane end-capped poly(tetramethylene oxide)
      (Si-PTMO)-modified CaO-SiO2 hybrids were successfully synthesized by hydrolysis
      and polycondensation of Si-PTMO, tetraethoxysilane (TEOS) and calcium nitrate. As
      for the samples with varying (Ca(NO3)2)/(TEOS) molar ratios under constant ratio
      of (Si-PTMO)/(TEOS) of 2/3 in weight. the apatite-forming ability in a simulated
      body fluid (SBF) which is indicative of bioactivity. remarkably increased with
      increasing CaO content, although the tensile strength and Young's modulus
      decreased. The hybrid with (Ca(NO3)2)/(TEOS) = 0.15 in mol formed an apatite on
      its surface within only 1 day. For this series of samples, the strain at failure
      which is a measure of capability for deformation of material, was found to be
      about 30% and almost independent of CaO content. As for the samples with varying
      (Si-PTMO)/(TEOS) weight ratios under constant ratio of (Ca(NO3)2)/(TEOS) of 0.15
      in mol, the strain at failure increased with increasing Si-PTMO content, but the
      apatite-forming ability, tensile strength and Young's modulus decreased. Thus,
      the synthesis of the hybrids exhibiting both high apatite-forming ability and
      high extensibility can be achieved by selecting suitable CaO and Si-PTMO
      contents. These new kind of hybrid materials may be useful as bioactive bone
      repairing materials.

PMID- 12069347
TI  - Osteoblast differentiation of bone marrow stromal cells cultured on silica gel
      and sol-gel-derived titania.
AB  - Primary cultures of osteogenic precursor cells derived from rat bone marrow
      stroma were performed on commercially available pure titanium discs (Ti c.p.) and
      surface modified Ti c.p.using a sol-gel technique (Ti sol). In separate repeated
      experimental runs, cell behavior and in vitro mineralization were compared with
      cultures on silica gel bioactive glass discs (S53P4). All substrates were
      incubated in simulated body fluid prior to the experiment. Overall, variable
      effects between experimental runs were seen. Apparently, this was due to the
      heterogeneous nature of the used cell population. Therefore, only careful
      conclusions can be made. Initial cell adhesion and growth rates between 3 and 5
      days of culture--analyzed by cell numbers--were in general comparable for the two
      titanium substrates, while initial growth up to day 3 is suggested to be higher
      in Ti c.p. compared to Ti sol. Although initial cell adhesion on the S53P4 glass
      discs was lower than the titanium substrates, cell growth rates appeared to be
      higher on the silica gel compared to the two titanium substrates. Further, there
      were some indications that the early and late osteoblast differentiation markers,
      alkaline phosphatase and osteocalcin, monitored up to day 24, were elevated in Ti
      c.p cultures compared to Ti sol cultures. There were no differences observed in
      in vitro mineralization between the titanium groups. S53P4 seemed to display a
      substantially higher differentiating capacity for both osteogenic cell markers as
      well as in vitro mineralization compared to the two titanium substrates.

PMID- 12069348
TI  - Effects of negatively charged groups (carboxymethyl) on the calcification of
      poly(2-hydroxyethyl methacrylate).
AB  - Poly(2-hydroxyethyl methacrylate) (pHEMA) has potentially wide biomedical
      applications: it is biocompatible, allows immobilization of cells or bioactive
      molecules and has a hardness comparable to bone. We previously reported that
      immobilization of alkaline phosphatase (AlkP) in pHEMA can initiate
      mineralization in a manner that mimics the calcification of cartilage and woven
      bone. Because numerous proteins known to initiate mineralization possess acidic
      species, we have modified the neutral electrical surface of pHEMA by
      carboxymethylation (CM). We have studied the effects of these negative groups on
      the calcification process in vitro. Calibrated pellets of pHEMA were prepared and
      carboxymethylated by soaking with 0.5 M bromoacetic acid in 2 M NaOH. Pellets of
      pHEMA, pHEMA-AlkP and pHEMA-CM were incubated during 5, 10 and 15 days in two
      types of body fluid: normal (1X) and 1.5X concentration of ions. Nodules of
      hydroxyapatite developed on pHEMA-AlkP and pHEMA-CM but not on pHEMA.
      Hydroxyapatite crystals were dissolved in HCl allowing calcium to be dosed. CM
      significantly increased the amount of deposited Ca by 1.8 folds in the 1X fluid
      and 15.8 folds in the 1.5X fluid. The presence of AlkP considerably increased the
      amount of deposited Ca: 25.9 folds in 1X and 23.3 in 1.5X. ROS 17/2.8 osteoblast
      like cells were seeded on the materials and examined by confocal microscopy after
      phalloidin staining. Cells grown on pHEMA alone appeared round, while cells grown
      on the crystals deposited on the pHEMA-CM or pHEMA-AlkP were flattened. The
      presence of AlkP favours the mineralization process more than the existence of
      surface negative groups on the polymer. Cells preferentially adhere to the
      polymer when hydroxyapatite crystals were developed.

PMID- 12069349
TI  - Health professionals' views of contracting for infection control in the NHS
      internal market.
AB  - This paper reports a national study which investigated the involvement of
      infection control professionals in (and their views about) the formal processes
      of contracting for health care in the NHS internal market. Health care
      professionals needed to be involved contracting, if it was to be effective. The
      study found that many infection control professionals were not, in fact, involved
      in contracting, while the importance of both contracts and informal professional
      networks were recognised But respondents did not think that their professional
      networks entirely compensated for their lack of involvement in contracting. As
      formal agreements continue to be central to achieving quality of care in the post
      internal market NHS, infection control professionals need to be involved in
      specification and implementation of these arrangements.

PMID- 12069350
TI  - Leadership development in health care: what do we know?
AB  - The NHS in England has developed a strong focus on clinical and managerial
      leadership. The article describes both emerging ideas on leadership models and
      approaches to developing leaders as a background to the description of two
      evaluation studies of leadership programmes for executive directors and the
      lessons learned for the future.

PMID- 12069352
TI  - Cross-sector working: speech and language therapists in education.
AB  - Current policies and practices concerning speech and language therapy provision
      in schools are reviewed and issues which remain to be addressed are considered A
      general move to cross-sector approaches has resulted in a move to indirect
      therapy through assistants, and the effectiveness of this requires to be
      established. Funding streams for therapy differ across the UK, and despite
      extensive research and policy development remain somewhat unclear and vulnerable.
      The implications for policies on 'joined up thinking" are considered.

PMID- 12069351
TI  - The moderators of patient satisfaction.
AB  - The purpose of this study was to determine which Department of Defense (DOD)
      active duty patient sociodemographic, health status, geographic location, and
      utilization factors, predict overall patient satisfaction with health care in
      military facilities. A theoretical framework developed from patient satisfaction
      and social identity theories and from previous empirical findings was used to
      develop a model to predict patient satisfaction and delineate moderating
      variables. The major finding indicated in this study was the significance of
      patients' characteristics in moderating their satisfaction. Principal components
      factor analysis and hierarchical linear regression revealed that patient specific
      factors predicted patients' satisfaction after controlling for factors depicting
      patients' evaluations of health system characteristics. Patient specific factors
      provided added, although very minimal, explanatory value to the determination of
      patients' satisfaction. The study findings can aid in the development of
      targeted, objectively prioritized programs of improvement and marketing by
      ranking variables using patients' passively derived importance schema.

PMID- 12069353
TI  - Cultural competency: professional action and South Asian carers.
AB  - Inequality and exclusion are characteristic of the experience of UK South Asian
      communities. In health care, community needs are often not addressed by health
      and social welfare services. An increase in cultural competency is now part of
      identified policy. The aim of this paper is to examine the extent to which there
      is evidence of cultural competency amongst professionals concerning South Asian
      parents caring for a person with cerebral palsy. Semi-structured interviews were
      conducted with respondents from 19 service organisations. Results are presented
      on perceptions of service delivery and on the dynamics of service development:
      evidence is found that inadequate service delivery continues despite professional
      knowledge that it exists. Conditions necessary for the achievement of cultural
      competence are discussed. We suggest that service development to meet the needs
      of South Asian carers must form part of an overall strategy geared to change at
      different levels within and outside service organisations.

PMID- 12069354
TI  - Managing performance and performance management: information strategy and service
      user involvement.
AB  - The involvement of service users is extolled in National Service Frameworks and,
      in Wales, is one of seven standards set out in the National Service Framework for
      mental health services. National Service Frameworks have an important role in the
      UK government's performance management strategies. The strategies are
      retrospective in effect and offer insufficient help for service managers and
      others seeking to change and improve service performance. Draws on research
      conducted at intervals over the past four years in Swansea. In today's devolved
      UK, the details will be different in Wales from elsewhere but the focus is on how
      a number of organisations with differing responsibilities can work together to
      manage performance improvement. Demonstrates that change requires leadership to
      be dispersed across organisational boundaries. Accountability and responsibility
      must be horizontal and even downwards, not just upwards to government Service
      users can b e involved in their own care. Surveys that involve service users in
      their planning stages can gather information about the service issues that matter
      to them. Managing performance is different from performance management. It can
      ultimately enable services users to initiate and direct some of the improvements
      they want to see and to take part in the processes of change. The information
      systems must be locally useful for all involved, and must offer information about
      performance in time to affect improvement and change.

PMID- 12069355
TI  - Myocardial function and effect of serum in isolated heart from
      hypertriglyceridemic and hypertensive rats.
AB  - We evaluated the myocardial function of rats with sugar-induced
      hypertriglyceridemia (HTG) and hypertension, and the effect of serum on
      myocardial performance in the isolated heart preparation. Also, the response to
      reperfusion after 30 minutes of global ischemia was investigated. Hearts from HTG
      rats developed lower ventricular pressure (VP) and the conduction rate was higher
      than in hearts from control rats (CR). The recovery of VP after ischemia was
      significantly lower in HTG than in CR hearts (p < 0.05). The HTG sera produced a
      higher increase in the VP and in the perfusion pressure. During reperfusion, the
      incidence of premature beats, ventricular fibrillation and tachycardia in HTG
      hearts was increased so hypertriglyceridemia caused alterations in the mechanical
      and electrical conduction of the myocardium and exacerbated the injury produced
      by ischemia-reperfusion. Also a circulating factor in the HTG serum induced a
      vasoactive response of the heart which was reflected in its mechanical
      performance.

PMID- 12069356
TI  - Self-measured systolic blood pressure in the morning is a strong indicator of
      decline of renal function in hypertensive patients with non-diabetic chronic
      renal insufficiency.
AB  - While blood pressure is a recognized major determinant of renal function
      deterioration, the role of self blood pressure measurement (BPM) in predicting
      the loss of renal function in hypertensive patients with chronic renal
      insufficiency (CRI) has not been adequately addressed. One hundred and thirteen
      patients (F/M: 46/67; 56 +/- 1 years) with CRI (mean serum creatinine: 1.87 +/-
      0.08; range: 1.4 to 3.5 mg/dl; average urinary protein excretion: 1.2 +/- 0.2
      g/24 hrs.) were followed for 3 years. The record of renal biopsy revealed that 74
      patients had IgA nephropathy, 16 had chronic glomerulonephritis, and 6 had
      membranous nephropathy, while 17, unbiopsied patients had underlying renal
      disease of unknown origin. Self BPM were made at regular intervals throughout the
      course of the study. All recorded blood pressures were included in a stepwise
      multiple regression analysis in which the decline in GFR per year was the
      dependent variable. Patients were primarily treated with a combination of
      amlodipine (5 to 20 mg daily), a calcium antagonist, and benazepril (2.5 to 5 mg
      daily), an ACE inhibitor in an effort to reduce their blood pressure at the
      office to < 130/85 mmHg. The simple correlation between blood pressures (i.e.,
      office, home morning and home evening) and the decline in GFR were all
      statistically significant. The correlation coefficients of determination for this
      model were as follows: r = 0.64 for home morning SBP; 0.43 for office SBP; 0.39
      for office DBP; and 0.38 for home morning DBP. The level of urinary protein
      excretion did not correlate with the decline in GFR. These data suggest that self
      BPM improves prognostic ability in hypertensive patients with CRI.

PMID- 12069357
TI  - Insufficient duration of action of antihypertensive drugs mediates high blood
      pressure in the morning in hypertensive population: the Ohasama study.
AB  - Blood pressure (BP) usually peaks in the morning. The circadian variation of the
      onset of cardiovascular disease mimics this circadian BP variation. To examine
      the determinants of the BP difference between the self-recorded BP in the morning
      (home BP) and daytime average ambulatory BP a cross sectional study was done in
      the general population of Ohasama, Japan. 1207 subjects > or = 20 years measured
      both home (more than 14 times) and ambulatory BPs (326 treated for hypertension
      and 881 untreated subjects), The prevalence of subjects with the systolic BP
      difference (home BP in the morning - daytime ambulatory BP) of > or = 10 mmHg
      (high morning BP) was 5.6% in untreated normotensives, 2.9% in untreated
      hypertensives, and 25.8% in treated hypertensives. This trend was also observed
      for diastolic pressure. Multiple regression analysis demonstrated that age, male
      sex, and use of antihypertensive drugs were positively associated and day-night
      difference of BP was negatively associated with the high morning BP,
      respectively. These results suggest an insufficient duration of antihypertensive
      action of widely used antihypertensive drugs in Japan from the 1980s to 1990s.
      The amplitude of the day-night difference of ambulatory BP in subjects with a
      high morning BP was lower (non-dipping) than that without high morning BP. The
      high morning BP is not necessarily accompanied by hypertension but might be
      mediated, at least in part, by an insufficient duration of action of
      antihypertensive drugs. The high morning BP accompanies so-called non-dipper
      pattern of circadian BP variation. An insufficient duration of action of drugs
      may partly mediate non-dipping in subjects with antihypertensive medication.

PMID- 12069358
TI  - Red blood cell Na+/H+ exchange activity is insulin resistant in hypertensive
      patients.
AB  - A number of ion transport defects have been described in human red blood cells
      (RBC) from patients with essential hypertension. Insulin resistance is also
      frequently present in hypertensive patients and insulin levels in vitro correlate
      with red blood cell Na+/H+ exchange (NHE) activity. We studied the kinetics of
      insulin-stimulated NHE activity in freshly isolated RBC from 14 patients with
      essential hypertension and 8 normotensive subjects. We measured an estimate of
      maximal activity (Vmax) for NHE activity as net Na+ influx driven by an outward
      H+ gradient in acid-loaded and Na+-depleted erythrocytes. NHE activity was
      significantly greater in hypertensives than in normotensives (22.0 vs 14.5 mmol/L
      cell x h, respectively; P<0.01). When RBC were pre-incubated with a physiologic
      dose of insulin (100 microU/mL), NHE activity increased significantly in both
      groups but the increase was greater in normotensives than in hypertensives (9.6
      vs 8.5 mmol/L cell x h, respectively; P < 0.05). Phosphatidylinositol-3 kinase
      (PI-3 kinase) inhibitors, wortmannin and LY294,002, had no effect on basal NHE
      activity but similarly and significantly inhibited insulin-stimulated NHE
      activity in both normal and hypertensive subjects. Insulin increased the Km for
      extracellular Na+ in normotensive subjects but not in hypertensive patients. In
      addition, the dose response curve for insulin and NHE activity showed that the
      curve for hypertensive patients was shifted rightward in relation to the
      normotensive subjects. These data suggest that insulin stimulates RBC NHE
      activity in vitro and this activation is mediated via a pathway that includes
      activation of PI-3 kinase. Hypertensive patients have elevated basal NHE activity
      but a blunted response to insulin suggesting that RBC may be a model to study
      insulin resistance in essential hypertensive patients.

PMID- 12069359
TI  - Elevated renal cortical calmodulin-dependent protein kinase activity and blood
      pressure.
AB  - The spontaneously hypertensive rat (SHR) exhibits not only hypertension but also
      behavioral hyperactivity which are not genetically linked. Two strains of rats,
      one hypertensive but normoactive (WKHT) and another, hyperactive but normotensive
      (WKHA), have been generated from SHR. We have reported that in renal proximal
      tubules, the linkage between D1-like receptors an adenylyl cyclase was impaired
      in SHR and WKHT but intact in WKHA. The impaired renal D1-like receptor function
      in the SHR was associated with increased phosphorylation of the D1 receptor,
      presumably caused by increased phosphorylation by G protein-coupled receptor
      kinases (GRK) or decreased dephosphorylation by protein phosphatase 2A. Because
      calmodulin kinase (CaMK) can regulate GRK activity, CaMK activity in renal
      cortical membranes of WKHA and WKHT were studied. We found that CaMK-dependent
      phosphorylation was two-fold higher in WKHA than in WKHT. In addition, serine
      phosphorylation of a 36 KDa and a 24 KDa protein was 5-fold and 3-fold greater in
      WKHA than in WKHT. We hypothesize that the increased CaMK activity in the renal
      cortical membrane may serve to inhibit GRK activity in WKHA and prevent the
      development of hypertension.

PMID- 12069360
TI  - Effects of fenoldopam, a dopamine D-1 agonist, and clevidipine, a calcium channel
      antagonist, in acute renal failure in anesthetized rats.
AB  - The present studies were conducted to: a) comparatively evaluate the effects of
      clevidipine, a new dihydropyridine calcium antagonist, and fenoldopam, a dopamine
      (D-1) receptor agonist on basal renal function, and b) to determine the efficacy
      of these agents in protecting renal function in an experimental model of
      ischemia/reperfusion (I/R) induced acute renal failure in rats. Infusions of
      either clevidipine or fenoldopam (5.0 nmol/kg(-1) min(-1) i.v. for 60 min)
      produced significant increases in urine flow (UV), urinary sodium excretion
      (UNaV), and fractional excretion of sodium (FENa) in inactin anesthetized rats.
      Unlike clevidipine, fenoldopam also produced significant increases in renal blood
      flow (RBF) and urinary potassium excretion (UKV). In a separate series,
      unilateral renal failure was induced in anesthetized rats by occluding the left
      renal artery for 40 min followed by reperfusion. In this model, there was a 70
      75% reduction in the GFR that was paradoxically associated with several fold
      increases in UV, UNaV, and FENa in the vehicle treated group. In two separate
      groups, infusions of neither clevidipine nor fenoldopam (5.0 nmol/kg(-1) min(-1))
      for 60 min beginning 10 min before reperfusion, improved filtration fraction.
      However, clevidipine treatment markedly improved tubular function in that loss of
      sodium and water were significantly attenuated and UV and UNaV were restored
      towards basal levels. In contrast, in the fenoldopam group, tubular function was
      further deteriorated as evidenced by exacerbated losses of sodium and water.
      These observations suggest that whereas both clevidipine and fenoldopam were
      potent natriuretic agents, only the calcium antagonist was effective in
      preserving renal function in the present experimental model of ischemic renal
      failure.

PMID- 12069361
TI  - Beneficial effect on blood pressure and lipid profile by programmed exercise
      training in Taiwanese patients with mild hypertension.
AB  - Mild essential hypertensive patients comprise a large portion of the hypertensive
      population. Previous reports have shown that moderate-intensity regular exercise
      training in these patients usually reduces blood pressure. By designing
      programmed exercise to evaluate whether it is effective in reducing blood
      pressure in mild hypertensive patients and also has beneficial effects on other
      biochemical parameters. Twenty-three mild hypertensive Taiwanese patients
      (resting blood pressure 139.1 +/- 11.4/99.5 +/- 8.0 mmHg) were divided randomly
      into two groups: control (no exercise) and moderate-intensity exercise (average
      6.4 +/- 0.7 METs). The training group exercised three times per week at the
      prescribed exercise intensity by using the Treadmill exercise test. Blood
      pressure, heart rate and other biochemical parameters were monitored regularly
      every 4 weeks for 12 weeks. After 12 weeks regular exercise training, the
      exercise group showed for significant resting blood pressure reduction. Mean
      maximal reduction of systolic pressure was 18 mmHg. Significant reduction of
      total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglyceride
      were found; elevation of high-density lipoprotein cholesterol (HDL-C) was also
      noted. These data suggest that after 12 weeks of exercise training in mild
      hypertensive patients, successful reduction of blood pressure and favorable
      changes of lipid profile will be noted.

PMID- 12069362
TI  - Research on irrelevance, helplessness, and immunization against helplessness in
      Spain: past, present, and future.
AB  - The main contribution to helplessness research in Spain was on immunization
      against helplessness and how it was modulated by predictability in animals or
      attributions in humans. Recent research have focused on factors determining the
      perception of non-contingency during learned irrelevance and the illusion of
      control during an uncontrollable experience. Its subsequent effects on
      covariation learning and the detection of controllability showed the influence of
      prior beliefs and attentional factors on covariation learning an learned
      helplessness whose influence should be integrated into current new learning
      models.

PMID- 12069363
TI  - Learned helplessness or learned inactivity after inescapable stress?
      Interpretation depends on coping styles.
AB  - Researches on uncontrollable events in the post-soviet states are overviewed. In
      our research, susceptibility to learned helplessness is studied in rats with
      active (KHA strain) versus passive (KLA strain) coping styles. Inescapable
      footshocks, but not escapable footshocks, applied to KHA rats induced escape
      failures, diminished locomotion and coping, reduced measures of anxiety, and
      resulted in dexamethasone nonsuppression of the brain-hypothalamus-pituitary
      adrenal axis--all characteristic of learned helplessness. In contrast, KLA rats
      demonstrated the same responses upon exposure to both escapable and inescapable
      stresses. While learned helplessness occurred in KHA rats, it appears that KLA
      rats exposed to inescapable stress demonstrated learned inactivity based upon the
      nondifference between effects of escapable and inescapable shocks. Relationships
      between coping styles and social ranks are discussed. Our and other's results
      with genetically selected strains suggest active coping in dominant and
      subordinate subjects, and passive coping in subdominant animals confirm the
      importance of coping style and its relation to health under stress.

PMID- 12069364
TI  - On learned helplessness.
AB  - "Learned helplessness" and its Pavlovian analog, learned irrelevance, are
      phenomena thought integral to understanding depression, PTSD, psychosomatic
      vulnerability, and a variety of diseases and immune disorders. The origin and
      development of research on learned helplessness is briefly overviewed with
      attention to the reasons for the controversy that surrounds the study of learned
      helplessness and derived physiological, psychological, and behavioral phenomena.
      The need to remedy past focus on American research and English language journals
      in this area is noted. The heuristic value as well as the wide ranging empirical
      value of the research domain is lauded. The meretricious emerging social and
      legal barriers to this research are noted to be unrealistic and unfortunate.

PMID- 12069365
TI  - Stressor controllability and learned helplessness research in the United States:
      sensitization and fatigue processes.
AB  - Recent work in the learned helplessness paradigm suggests that neuronal
      sensitization and fatigue processes are critical to producing the behavioral
      impairment that follows prolonged exposure to an unsignaled inescapable stressor
      such as a series of electric tail shocks. Here we discuss how an interaction
      between serotonin (5-HT) and corticosterone (CORT) sensitizes GABA neurons early
      in the pretreatment session with inescapable shock. We propose that this process
      eventually depletes GABA, thus removing an important form of inhibition on
      excitatory glutamate transmission in the amygdala, hippocampus, and frontal
      cortex. When rats are re-exposed to shock during shuttle-escape testing 24 hrs
      later, the loss of inhibition (as well as other excitatory effects) results in
      unregulated excitation of glutamate neurons. This state of neuronal over
      excitation rapidly compromises metabolic homeostasis. Metabolic fatigue results
      in compensatory inhibition by the nucleoside adenosine, which regulates neuronal
      excitation with respect to energy availability. The exceptionally potent form of
      inhibition associated with adenosine receptor activation yields important
      neuroprotective benefits under conditions of metabolic failure, but also
      precludes the processing of information in fatigued neurons. The substrates of
      adaptive behavior are removed; performance deficits ensue.

PMID- 12069366
TI  - The effects of uncontrollable, unpredictable aversive and appetitive events:
      similar effects warrant similar, but not identical, explanations?
AB  - Exposure to uncontrollable, unpredictable appetitive events produces a variety of
      cognitive debilitations and vegetative changes, as does exposure to
      uncontrollable, unpredictable aversive events. Similarities include impaired
      escape from aversive events, impaired discrimination, finicky consumption,
      analgesia, and body weight loss. However, in stark contrast, uncontrollable
      aversive stress causes reduced motor activity where as similar appetitive
      treatment does not; aversively induced debilitation is causally related to energy
      regulation, whereas the appetitively induced effects are not. Parallel mechanisms
      are suggested to explain these effects in terms of a revised anxiety account of
      the aversive effects, and a frustration account of the appetitive effects.
      Finally, factors likely to limit important research to resolve the many remaining
      issues are identified: negative presentation of animal research, political
      decision making, and ignorance and fear in committees which review the ethics of
      research.

PMID- 12069367
TI  - Recent learned helplessness/irrelevance research in Japan: conceptual framework
      and some experiments on learned irrelevance.
AB  - In Section 1, a conceptual framework within which to study learned helplessness
      (LH), learned irrelevance (LI) and the related phenomena is introduced. In
      Section 2, three rat experiments on LI conducted in our laboratory using a
      conditioned suppression of licking preparation are introduced. In Experiment 1,
      the phenomena of LI and general LI were confirmed. In Experiment 2, random
      presentations of CST/US were found to interfere with subsequent initial
      excitatory conditioning to CSL under random CSL/US presentations. In Experiment
      3, pre-paired presentations of CSN or CST with US before random CST/US
      presentations was found to have an attenuating effect on the development of
      general LI.

PMID- 12069368
TI  - Effect of cod liver oil on symptoms of rheumatoid arthritis.
AB  - In this pilot study, 43 patients with rheumatoid arthritis ingested 1 g of cod
      liver oil (one capsule) daily for 3 months. Decreases occurred in morning
      stiffness (52.4%; P<10(-3)), painful (42.7%) and swollen (40%) joints (P= 10(-3)
      each), and pain intensity (67.5%). Ratings of "good" or "very good" were awarded
      by 68% of the patients for efficacy and by 95% for tolerability. Eleven patients
      reported nonsevere adverse effects that in 3 cases may have been related to the
      study preparation. Cod liver oil can be recommended for the treatment of
      rheumatoid arthritis.

PMID- 12069369
TI  - Future directions in lipid therapies.
AB  - Cholesterol management to reduce the burden of cardiovascular disease is a major
      public health concern. Despite widespread recognition of lipid abnormalities as
      cardiovascular risk factors, significant cardiovascular event reductions with
      cholesterol-lowering therapies, and dissemination of treatment guidelines, most
      high-risk patients are not at target lipid levels. In addition to lifestyle
      changes, four major drug classes are available to modify lipid levels: fibrates,
      niacin, resins, and statins. High efficacy and tolerability in clinical trials
      make statins the most widely prescribed of these agents. Newer, more potent
      members of this class and novel formulations of niacin and resins may provide
      more effective therapy for dyslipidemia with fewer side effects. Several agents
      in development (cholesterol-absorption inhibitors and ACAT inhibitors) exploit
      mechanisms of action complementary to those of current treatments and combined
      with statins may produce greater improvements in lipid profiles than are now
      possible. These innovations should enable a greater number of patients to achieve
      more aggressive cholesterol goals, thereby reducing the risk of cardiovascular
      events.

PMID- 12069370
TI  - Nedocromil sodium ophthalmic solution 2% twice daily in patients with allergic
      conjunctivitis.
AB  - In a multicenter, open-label evaluation, 1098 patients with ocular itching and a
      history of perennial or seasonal allergic conjunctivitis instilled one drop of
      nedocromil sodium 2% twice daily in each eye. Ocular symptoms, signs, and global
      improvement were assessed at baseline and 1 month; satisfaction scores, quality
      of-life variables, and adverse events were also recorded. Significant
      improvements from baseline (P<.012) occurred in mean severity scores for itching,
      burning, stinging, watering, swelling, tired eyes, dryness, gritty sensation, eye
      pain, foreign-body sensation, and light sensitivity. Physicians reported
      significant reductions (P<.0001) in bulbar conjunctival redness and swelling. Two
      thirds of patients (634/954) and three fourths of physicians (710/954) reported
      at least 75% improvement in overall condition after 1 month. The most common
      adverse events were burning (2.7%) and unpleasant taste (1.4%); headache (1.2%)
      and adverse events leading to discontinuation (1.3%) were rare. Patients reported
      significant improvement (P<.001) in their ability to perform daily activities;
      65% were more satisfied with nedocromil than with their typical medication.
      Physicians would prescribe nedocromil again to 80% of the patients. Nedocromil
      sodium 2% twice daily was effective and safe for the treatment of symptoms of
      allergic conjunctivitis, significantly improving quality of life and producing
      high rates of user and physician satisfaction.

PMID- 12069371
TI  - Phosphorylation of Helicobacter pylori CagA in patients with gastric ulcer and
      gastritis.
AB  - The effects of Helicobacter pylori infection are strongly associated with chronic
      gastritis, gastric and duodenal ulcer, gastric cancer, and MALT lymphoma. The
      microorganism has been classified as a type I carcinogen by the World Health
      Organization. Varying clinical results from H. pylori infection are believed due,
      in part, to differences in virulence among species. The cag pathogenicity island
      is a complex of virulent genes and a coding region for the type IV phosphorylated
      secretion system. Through this system, many virulent gene products or proteins
      are phosphorylated into the host cells. This study demonstrated the positive CagA
      phosphorylation effect of H. pylori in patients with chronic gastritis and benign
      gastric ulcer and revealed significantly different rates of CagA phosphorylation
      between these two diseases (P<.05).

PMID- 12069372
TI  - Brimonidine .2% as a replacement for beta blockers in geriatric patients with
      glaucoma.
AB  - This 3-month multicenter, open-label study of 89 geriatric patients with glaucoma
      evaluated the substitution of brimonidine twice daily for topical beta blockers
      that had been used for at least 6 months. The primary outcome measures were
      reduction in intraocular pressure (IOP) from baseline at 2 hours postdose, change
      in cardiac and respiratory function, quality of life, and patient satisfaction.
      Patients were queried about adverse events at each visit and completed a quality
      of-life questionnaire at the final evaluation. In this cohort with a mean age of
      75.4 years, the average duration of topical beta-blocker therapy was 5 years.
      Brimonidine twice daily produced an additional mean reduction in IOP of 8.2% (1.4
      mm Hg; P<.001). Eighty-eight percent of patients (60/68) reported being at least
      as satisfied with brimonidine as with their previous beta-blocker regimen, and
      46% (31/68) reported greater satisfaction with brimonidine. Additionally, 40% of
      patients (27/68) noted increased energy after the switch, and 43% (29/68)
      described brimonidine as more soothing than topical beta blockers. In this
      elderly population, the replacement of topical beta blockers with brimonidine
      twice daily significantly decreased IOP, improved quality of life, and enhanced
      patient satisfaction.

PMID- 12069374
TI  - The development of cytokine receptor antagonists as potential therapeutic agents
      for the myeloproliferative disorders.
AB  - The aetiology of the myeloproliferative disorders and, in particular, of the
      myeloid leukaemias is unknown. The transformation of cells is primarily due to
      molecular aberrations leading to excessive cellular signalling and proliferation.
      In addition cytokines and their receptors may play a role in leukaemogenesis by
      increasing the proliferative capacity of leukaemic cells and extending their life
      span. Chemotherapeutic agents are regularly used to treat patients with leukaemia
      but they are non-discriminatory treatments that kill both healthy and cancer
      cells. Consequently patients receiving chemotherapy suffer unwanted toxicities in
      both the haematological and other systems. Therapies that specifically target
      malignant cells sparing normal cells are being investigated in a number of
      contexts. Cytokine antagonists can target growth factor-dependent cells by
      obstructing the interaction between cytokine and receptor. In this review we will
      discuss the myeloproliferative disorders in particular the leukaemias, the
      cytokines involved in leukaemogenesis, and the therapeutic potential of new
      agents that block specific cytokines.

PMID- 12069373
TI  - The use of hematopoietic growth factors in the treatment of acute leukemia.
AB  - Cytokines are centrally involved in the regulation of normal hematopoiesis, the
      production of mature blood cells by bone marrow stem cells. Cytokines influence
      stem survival, proliferation, and differentiation commitment, as well as
      controlling the orderly maturation of progenitor cells into functional
      leucocytes, erythrocytes, and platelets. Acute leukemias result from malignant
      transformation of bone marrow stem cells. Although cytokines do not appear to be
      centrally involved in the pathogenesis of acute leukemias, leukemic cells express
      receptors for many of the cytokines regulating normal hematopoiesis, particularly
      G-CSF, GM-CSF, IL-3, and stem cell factor. These molecules have demonstrable
      effects on acute leukemia cells in vitro, inducing proliferation and enhancing
      survival, but their biological activity when administered as recombinant proteins
      in pharmaceutical doses to patients with active leukemia are less well
      understood. Because of the stimulatory effects of cytokines such as G-CSF and GM
      CSF on normal hematopoiesis in vitro and in normal individuals, these two
      molecules have been extensively studied in randomised clinical trials of
      chemotherapy for cancer, including acute leukemia. Concerns about the potential
      for G-CSF and GM-CSF to accelerate the growth of acute myeloid leukemia, which
      expresses receptors for both molecules, have not been realised. Conversely, the
      concept of using either of these two cytokines to induce acute myeloid leukemia
      cells into active DNA synthesis, thus potentially sensitising them to the effects
      of S-phase-specific drugs, has not been shown to be clinically beneficial. Both G
      CSF and GM-CSF have been demonstrated to accelerate the recovery of normal
      granulopoiesis after intensive initial cytotoxic chemotherapy for acute leukemia,
      significantly shortening the duration of severe treatment-induced neutropenia,
      and resulting in a number of tangible benefits including reduction in infection,
      use of intravenous antibiotics, and duration of hospital stay. However, the final
      role for these agents in the treatment of acute leukemia remains controversial
      and still to be fully defined.

PMID- 12069375
TI  - The impact of thrombopoietin on clinical practice.
AB  - Prevention of hemorrhage secondary to thrombocytopenia has generally been managed
      by the transfusion of platelets. The need for such transfusion is related to the
      depth and duration of "critical" thrombocytopenia, a level that until recently
      was hotly debated. However a number of clinical trials have established that
      transfusion at a platelet count greater than 10 x 10(9)/L was safe in the absence
      of factors associated with increased tendency to bleed. Trying to predict which
      patients are at risk of bleeding due to thrombocytopenia has proven difficult
      outside of those scenarios that inevitably cause severe thrombocytopenia, such as
      treatment of leukemia and myeloablative chemotherapy with stem cell support.
      Models have been proposed but have yet to be validated. Of greater importance is
      the need for proof that intensive treatment of solid tumours with growth tactor
      support leads to improved outcomes. The discovery of platelet growth factors
      raised expectations that an effective method for abrogating thrombocytopenia
      would be soon available in the clinic. The cytokines initially described were
      pleiotropic in nature, and stimulation of platelet production was generally
      modest. However, one of these agents, interleukin-11, was successfully shown to
      reduce the incidence of severe thrombocytopenia in patients receiving dose
      intensive chemotherapy, and has now received approval from the FDA for this
      purpose. Initial clinical trials of thrombopoietin (TPO), the central regulator
      of megakaryocytopoiesis and thrombopoiesis, and its analogues showed these agents
      to be the most potent stimulators of thrombopoiesis and to be associated with few
      adverse effects. They have also been shown to enhance platelet recovery after
      chemotherapy, but early results from trials investigating their ability to
      prevent severe thrombocytopenia associated with the treatment of leukemia and
      bone marrow transplantation have been disappointing. In addition, subcutaneous
      administration of one of these agents, megakaryocyte growth and development
      factor, has been shown to induce the formation of antibodies that neutralize
      native TPO and cause thrombocytopenia. TPO remains a promising therapeutic agent,
      however its potential application is more limited than initially anticipated, and
      there are a number of obstacles to overcome before it finds an importance use in
      the clinic.

PMID- 12069376
TI  - Cytokines in haemopoietic progenitor mobilisation for peripheral blood stem cell
      transplantation.
AB  - Haemopoietic progenitors mobilised into peripheral blood are now almost
      universally used in autologous haemopoietic stem cell transplantation in the
      treatment of a range of malignant and some nonmalignant disease. Although
      chemotherapy alone was initially used, all modern protocols now involve the use
      of cytokines, with or without chemotherapy. Important developments have included
      an in understanding of the importance of prior cancer therapy on progenitor
      yield, knowledge of the kinetics of mobilisation and development of necessary
      skills to collect and cryopreserve progenitors. More accurate measurement of
      haemopoietic progenitors and definitions of target cell yields for optimal
      haemopoietic recovery after high-dose therapy have also contributed to more
      predictable outcomes and provide a reference point for newer mobilisation
      approaches. Although G-CSF based regimens are usually successful, some patients
      either fail to mobilise sufficient progenitors or require an excessive number of
      collections. Clinical studies with the early acting cytokine, stem cell factor,
      in combination with G-CSF have demonstrated increased progenitor yields in a
      range of patients which may translate to clinical benefit in selected situations.
      In animal models and to a lesser extent in humans, other cytokines such as
      thrombopoietin and Flt-3 ligand or a number of engineered small molecules with
      single or dual agonist activity for cytokine receptors (IL-3, Flt-3L, TPO, G
      CSF), have also been found to be promising mobilising agents. Further research
      into the relative importance of cell proliferation, cellular adhesion and the
      role of accessory cells and other signalling events is leading to an improved
      understanding of the underlying mechanisms of haemopoietic progenitor
      mobilisation. Administration of appropriate high-dose chemotherapy followed by re
      infusion of haemopoietic progenitor cells capable of long-term reconstitution has
      long had a place in the treatment of a number of malignant (largely
      haematological) and non-malignant diseases. For many years these progenitor cells
      were obtained by direct aspiration of bone marrow under general anaesthetic,
      hence the term bone marrow transplantation. However, it has also been recognized
      that haemopoietic stem cells may be recovered from peripheral blood, albeit in
      low numbers, and also from umbilical cord blood. Further empirical observations
      showed that the number of haemopoietic progenitors circulating in the blood could
      be transiently augmented after chemotherapy and/or administration of one or more
      of a number of cytokines. Refinements to the clinical practice of progenitor
      mobilisation, collection and enumeration have proved very successful such that in
      many cases peripheral blood stem cells (PBSC) have largely replaced bone marrow
      as the preferred source.

PMID- 12069377
TI  - Keratinocyte Growth Factor (KGF) in hematology and oncology.
AB  - Keratinocyte Growth factor (KGF) is an epithelial cell growth factor of the
      fibroblast growth factor family and is produced by fibroblasts and microvascular
      endothelium in response to proinflammatory cytokines and steroid hormones. KGF is
      a heparin binding growth factor that exerts effects on epithelial cells in a
      paracrine fashion through interaction with KGF receptors. Preclinical data has
      demonstrated that KGF can prevent lung and gastrointestinal toxicity following
      chemotherapy and radiation and preliminary clinical data in the later setting
      supports these findings. In the experimental allogeneic bone marrow transplant
      scenario KGF has shown significant ability to prevent graft-versus-host disease
      by maintaining gastrointestinal tract integrity and acting as a "cytokine shield"
      to prevent subsequent proinflammatory cytokine generation. Within this setting
      KGF has also shown an ability to prevent experimental idiopathic pneumonia
      syndrome by stimulating production of surfactant protein A, promoting alveolar
      epithelialization and attenuating immune-mediated injury. Perhaps most
      unexpectantly, KGF appears able to maintain thymic function during allogeneic
      stem cell transplantation and so promote T cell engraftment and reconstitution.
      These data suggest that KGF will find a therapeutic role in the prevention of
      epithelial toxicity following intensive chemotherapy and radiotherapy protocols
      and in allogeneic stem cell transplantation.

PMID- 12069379
TI  - Cytokine manipulation of the immune response in the treatment of human acute
      leukaemia.
AB  - Myeloid leukaemia cells are sensitive to attack by elements of the immune system
      as evidenced by the effects of T cell depletion, graft versus leukaemia and donor
      lymphocyte infusion on leukaemic recurrence. An implication is that the immune
      system can be manipulated to enhance anti-leukaemic effects by exogenous
      stimulation including the use of immunostimulatory cytokines. These could
      potentially be used in a controlled manner that avoids the clinical problems
      associated with graft-versus-host disease. The cytokine used most extensively to
      date is interleukin-2 (IL2), a molecule that induces T lymphocyte proliferation
      and the generation of MHC unrestricted cytotoxicity. Despite over 10 years of
      clinical experience, the data on efficacy in acute myeloid leukaemia remains
      unclear due to lack of adequate randomised trials. IL2 appears to be effective in
      patients with low level marrow infiltration by acute myeloid leukaemia (AML)
      blast cells. It is less effective when patients present or relapse with packed
      bone marrows. The logical assumption that IL2 treatment given during states of
      minimal residual disease will reduce the incidence or speed of disease recurrence
      remains to be adequately tested. IL2 administration is associated with
      characteristic clinical adverse effects and with specific immuno-haematological
      changes. The use of other cytokines for immune manipulation in patients with AML
      is so far essentially limited to the research laboratory. Potential uses include
      cytokine induced blast differentiation to dendritic cells and the use of
      irradiated cytokine gene transduced leukaemic cells as vaccines.

PMID- 12069378
TI  - Growth factors, cytokines and dendritic cell development.
AB  - Dendritic cells (DC) initiate tumor specific immune responses in animal studies
      and initial human trials suggest that certain tumor-antigen loaded DC
      preparations generate clinical responses. DC may be obtained from blood or
      generated in vitro from precursor cells. In vitro generation of DC from precursor
      cells, under the influence of cytokines, has been favoured to date as a source
      because of the greater numbers of DC produced. However, the different cytokine
      combinations and serum or plasma component(s) used, differentiate precursor cells
      into DC with different physiological properties and ultimate immunogenicity.
      Thus, the quality of in vitro cytokine derived DC may have a profound influence
      on clinical outcomes. The administration of certain growth factors, which
      increase the number of circulating blood DC, may provide an alternative source of
      DC for use in clinical trials. Although clinical trials in prostate cancer,
      melanoma and metastatic renal carcinoma patients are encouraging, some data
      suggest certain DC preparations and administration protocols are sub optimal,
      even potentially tumor enhancing. As basic scientific studies establish how to
      provide DC with stable phenotype, resistance to tumour inhibitory factors and
      high migratory capacity, the technology for producing cytokine derived DC in
      vitro using Good Manufacturing Practise (GMP) conditions needs to be developed.
      Future DC vaccination protocols will require careful control of the DC used for
      tumor-antigen loading and repetitive long term DC vaccination may be necessary to
      maintain effective anti-tumor immune responses.

PMID- 12069380
TI  - Drug delivery system of anti-fungal and parasitic agents.
AB  - The antifungal agents for systemic mycoses are only a few in number. Among them
      amphotericin-B is still the most widely used drug, but substantial side effects
      including nephrotoxicity limits its clinical usefulness. Efforts to lower the
      toxicity are synthesis of AMPH-B analogues such as AMPH-B esters and
      encapsulation in lipid vesicles in the forms of liposomal AMPH-B (AmBisome),
      amphotericin-B lipid complex (Abelcet), amphotericin-B colloidal dispersion
      (Amphocil) and intralipid AMPH-B. The newer formulations are effective against
      wide range of fungi, may be given in higher doses and nephrotoxicity is lowered.
      Although all of them showed comparable efficacies, a standard formulation is yet
      to be determined. In Japan, studies on efficacies of lipid nanosphere
      encapsulated AMPH-B are in progress. Special drug career systems and dosage
      forms, such as nanoparticles and liposomes hold the promise of overcoming the
      pharmacokinetic limitations. Nanoparticles are stable, solid colloidal particles
      consisting of macromolecular material and vary in size. Nanoparticles represent
      an interesting carrier system for the specific enrichment in macrophage
      containing organs like liver and spleen. Injectable nanoparticle carriers have
      important potential applications as in site-specific drug delivery. Modifications
      of liposomes in order to avoid uptake by RES, thus increase targetability has
      been attempted. A novel targetable liposome 34A-PEG-L modified with polyethylene
      glycol conjugated with MoAb, 34A specific to murine pulmonary epithelia has been
      evaluated in murine pulmonary aspergillosis. 34A-PEG-L-AmB showed higher tissue
      concentration and comparable efficacy than other AMPH-B formulations.

PMID- 12069381
TI  - Pharmaceutical design of the liposomal antimicrobial agents for infectious
      disease.
AB  - From the point of view of pharmaceutical design, development of carrier system of
      antimicrobial agents with functional properties should be required. We introduced
      here the development-process of liposomal formulations of polyene macrolide
      antibiotics, amphotericin B (AmB) and nystatin as injectable dosage forms. Both
      development of the effective encapsulation method of these drugs in liposomes and
      investigation of the encapsulation mechanism and the molecular states of them are
      important to determine the optimum lipid composition for therapeutic uses.
      Enhanced encapsulation of these hydrophobic drugs, long-circulation in blood and
      high targetability are the required functional properties for the carrier system.
      Low encapsulation of AmB in liposomes has been overcome by the incorporation of
      polyethylene glycol-lipid derivatives, DSPE-PEG. Both the hydration with 9%
      sucrose solution and the complex formation between AmB and DSPE-PEG contribute
      not only to the enhanced encapsulation of AmB in liposomes but also to the
      stability and long-circulation properties in blood. Encapsulation mechanism and
      the molecular states of AmB in liposomes were also investigated by several
      methods. AmB-encapsulating PEG liposomes (PEG-L-AmB) with optimum lipid
      composition also showed reduced toxicity and higher therapeutic efficacy on
      murine model of pulmonary aspergillosis than that of conventionally used AmB
      formulations. Further enhanced therapeutic effects was observed by using AmB
      encapsulating PEG immunoliposomes (34A-PEG-L-AmB) carrying monoclonal antibodies
      at the distal ends of the PEG chains. On the contrary to AmB, encapsulation
      characteristics of nystatin were apparently different from that of AmB, though
      the chemical structure is very similar. Self-association of nystatin with sterol
      free lipid membrane dominantly influences on the encapsulation characteristics.
      Many experiments about the encapsulation of antimicrobial agents in liposomes
      have been demonstrated by many researchers, but there are not so much drugs
      developed for commercially used. Optimization of the formulation of functional
      drug-carrier system should be important for the practical uses.

PMID- 12069382
TI  - Drug delivery system to control infectious diseases.
AB  - Viral replication takes place only in the host cell. From this intrinsic
      characteristics of virus, therapeutics agents specifically target to the virus
      genome is quite difficult. However, genetic medicine toward viral gene is
      promising in terms of selective toxicity for viral infection. Genetic medicine
      including antisense DNA, ribozyme, aptamer, triplex and gene itself has been
      enthusiastically studied in the past decades. At the early age of genetic
      medicine research, there were many skepticisms about clinicla usage. However, the
      first antisense DNA is on the market in the USA and Europe. Although the
      mechanism of antisense manner is still controversial, it was clearly epoch-making
      in the human application of genetic medicine. Genetic medicine opens the
      possibility to combat virus replication in a sequence specific way. Virus
      utilizes the specific receptor on the host cells for entry; this is the reason
      why virus has organ specificity (tropism). Since life cycle of each virus is
      unveiled, target for the therapeutic agent's reveals in a molecular level.
      Furthermore, decipher of viral genome has been carried out rapidly and
      inexpensively. Once we hand entire sequences of viral genome, more theoretical
      way to design genetic medicine targeted viral infection could be main stream in
      the development of antiviral agents. Furthermore, efficient drug delivery system
      (DDS) to deliver antiviral agents to the infectious site is highly needed. In
      this article, we will address the target molecule of antiviral agents and
      possible DDS for the infectious disease.

PMID- 12069383
TI  - Lipid formulation as a drug carrier for drug delivery.
AB  - In recent years, a Drug Delivery System (DDS), a preparative approach attracts
      the attention in the development of new drugs. DDS focuses on the regulation of
      the in vivo dynamics, such as absorption, distribution, metabolism, and
      elimination, thereby improving the effectiveness and the safety of the drugs by
      an applicable use of drug preparation technologies. A conventional intravenous
      dosage form of Amphotericin B (AmB), Fungizone, is the most effective clinically
      available for treating fungal infections. However, the clinical efficacy of AmB
      is limited by its adverse effects. Several lipid formulations, such as Liposomal
      AmB (L-AmB), AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD), with
      reduced side effects have been developed. These formulations are reported to have
      excellent safety and efficacy. However, comparable efficacy can be achieved only
      when they are administered at high doses than AmB. One of the problems of using
      these formulations is that they are easily taken up by the reticuloendothelial
      system (RES). An artificial lipoprotein-like particles, a novel drug carrier
      Lipid Nano-Sphere (LNS), which is 25 - 50 nm in size and is composed of
      phospholipids and simple lipid. LNS show a higher plasma concentration of drugs
      and lower uptake by RES-tissue different forms other lipid base drug carriers. In
      vitro and in vivo, LNS incorporating AmB, NS-718, shows reduced toxicity, while
      maintaining activity against fungi. LNS have a unique characteristic as an
      effective carrier of AmB for treatment of fungal infection.

PMID- 12069384
TI  - Design of anti-bacterial drug and anti-mycobacterial drug for drug delivery
      system.
AB  - Liposome-encapsulated drugs often exhibit reduced toxicity and have also been
      shown to enhance retention of drugs in the tissues. Thus, encapsulation of drugs
      in liposomes has often resulted in an improved overall therapeutic efficacy. The
      results of efficacy of liposome-encapsulated ciplofloxacin or azithromycin for
      therapy of intracellular M. avium infection show enhanced cellular delivery of
      liposome-encapsulated antibiotics and suggest that efficiency of intracellular
      targeting is sufficient to mediate enhanced antimycobacterial effects. The
      antitubercular drugs encapsulated in lung specific stealth liposomes have
      enhanced efficacies against tuberculosis infection in mice. These results from
      stealth liposome study indicate that antitubercular drugs encapsulated in
      liposome may provide therapeutic advantages over the existing chemotherapeutic
      regimen for tuberculosis. Liposomes with encapsulated amikacin are able to
      protect collagen almost completely from adherence of bacterial cells of all
      strains examined and prevent from invading of bacteria.

PMID- 12069385
TI  - Might wasp venom desensitization induced Th2 to Th1 shift cause pregnancy
      failure?
AB  - The case of a 28-year-old woman under wasp venom desensitization having a
      premature birth in her 24th week of pregnancy 16 days after the last injection is
      described. To test the hypothesis that a special profile of immune cells in the
      decidua may trigger abortions, placental and decidual tissue sections were
      stained with antibodies against T cells (CD3), cytotoxic cells (CD8), natural
      killer cells (CD56), and mast cells, and an in-situ-hybridization was performed
      for tumor necrosis factor-alpha (TNF-alpha). CD56+ Natural killer cells were the
      dominating population. In earlier analyses of healthy first trimester decidua the
      percentage of NK cells and T cells was in a similar range, but the CD8:CD3 ratio
      was only 2.2% in contrast to 27% in the present case. Mast cells, which are known
      to be able to secrete abortogenic TNF-alpha, were only detectable in the decidua
      (10 cells/mm2) and decidua sections were TNF-alpha positive. Since SIT induces a
      shift of the interleukin and functional profile from a Th2 type towards a Th1
      type, and pregnancy is dependent on a Th2 pronounced profile, SIT may trigger
      abortions or immature births. This is supported by the present results and might
      have happened in this case.

PMID- 12069386
TI  - Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail
      to predict pregnancy outcome following recurrent abortion.
AB  - PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes
      from patients with histories of recurrent abortion to predict outcome of
      subsequent pregnancy. METHODS OF STUDY: Seventeen women with two successive
      spontaneous abortions with normal karyotype in the conceptus and 15 women with
      male-factor infertility were studied. Subsequent pregnancy outcomes in 17
      recurrent abortion patients were noted; 11 had live birth, while six aborted in
      the first trimester. All of 15 women with male-factor infertility became pregnant
      after therapy, resulting in live birth in all cases. Endometrium was sampled
      during the peri-implantation period before subsequent pregnancy. We immunostained
      paraffin-embedded sections for lymphocyte markers including natural killer (NK)
      cell markers, CD56 and CD16, a B-cell marker CD20, T-cell markers CD3 and CD8,
      and a specific T-helper(Th)2 and T-cytotoxic (Tc)2 marker termed 'chemoattractant
      receptor-homologous molecule expressed on Th2 cells' (CRTH2). Immunoreactive
      cells for these antigens were counted and positivity ratios to CD45- or CD3
      positive cells were calculated. These parameter were compared between 17 patients
      with histories of recurrent abortion and 15 control women and also compared
      between 11 patients whose subsequent pregnancy was successful and six patients
      whose subsequent pregnancy was a failure. RESULTS: Numbers of CD45+, CD56+,
      CD16+, CD20+, CD3+, CD8+, and CRTH2+ cells in recurrent abortion patients
      resembled those in controls. No significant difference in lymphocyte subset
      numbers or ratios was noted between patients whose subsequent pregnancy was
      successful and those who again aborted. CONCLUSION: We could not predict
      pregnancy outcome by immunophenotypic analysis of endometrium in women with
      recurrent abortion.

PMID- 12069387
TI  - An optimized technique for separation of human decidual leukocytes for cellular
      and molecular analyses.
AB  - PROBLEM: Human decidua contains a significant number of leukocytes,
      phenotypically and functionally different from peripheral blood. In vitro studies
      of decidual leukocytes require constant improvement of cell isolation technique
      in order to obtain highly purified viable and functionally active cells. METHOD
      OF STUDY: Optimized isolation procedure of decidual leukocytes, based on non
      enzymatic cell dispersion, Percoll gradient centrifugation and purification step
      involving immunomagnetic beads is compared with a similar procedure with
      Lymphoprep gradient. RESULTS: The method based on Percoll gradient gave a viable
      leukocyte fraction with higher amount of alphabetaT- and gammadeltaT cells
      compared with Lymphoprep gradient. The leukocytes exhibited a well-preserved
      ultrastructure and surface marker expression and were suitable for molecular
      analysis. The magnitude and the kinetics of their proliferative response were
      comparable with peripheral blood lymphocytes. CONCLUSIONS: The results provide an
      optimized method for isolation and enrichment of decidual leukocytes, suitable
      for phenotypic, ultrastructural, molecular and functional analyses.

PMID- 12069388
TI  - Uterine chemokines in reproductive physiology and pathology.
AB  - PROBLEM: Chemokines are increasingly recognized as important regulators of
      uterine function. METHODS OF STUDY: The following is a review of uterine
      chemokines, especially monocyte chemotactic protein (MCP)-1, interleukin (IL)-8,
      and regulated-upon-activation normal-T-cell-expressed and -secreted (RANTES)
      protein, in reproductive physiology and pathology. RESULTS: It is increasingly
      clear that IL-8, MCP-1, RANTES and their receptors are produced by endometrial,
      myometrial, and trophoblast cell types in a timed and co-ordinated manner. In
      addition to the regulation of leukocyte migration and function, uterine
      chemokines also display specific roles in endometrial angiogenesis, apoptosis,
      proliferation, and differentiation. IL-8, MCP-1 and RANTES are regulated by local
      growth factors and cytokines such as tumor necrosis factor-alpha (TNF-alpha),
      interferon-gamma, and IL-1. IL-8 takes part in cervical ripening and parturition.
      IL-8, MCP-1 and RANTES are also found at high levels in the peritoneal fluid of
      women with endometriosis. CONCLUSION: Co-ordination of chemokine-chemokine
      receptor interactions plays an important role in the menstrual cycle and
      successful pregnancy. Moreover, unbalanced chemokine expression contributes to
      pathologic conditions typified by uncontrolled cellular proliferation, migration
      and invasion.

PMID- 12069389
TI  - Interleukin 2 receptor gamma chain (gamma(c)) knockout mice show less regularity
      in estrous cycle but achieve normal pregnancy without fetal compromise.
AB  - PROBLEM: Implication of cytokines in pregnancy suggested but remains to be
      established. We studied the effect of cytokines on reproductive functions such as
      ovulation and pregnancy, with mutant mice lacking interleukin 2 receptor gamma
      (IL-2Rgamma), the so-called common gamma chain (gamma(c)), which is shared among
      receptors for multiple cytokines such as IL-2, IL-4, IL-7, IL-9 and IL-15. METHOD
      OF STUDY: Regularities of estrous cycles were observed by vaginal smear. Ovaries
      stimulated with postmenopausal serum gonadotropin (PMSG) were examined for the
      ovarian capacities. The uteri at 13 days of gestation were used for histological
      analysis of the maternal-fetal interface. RESULTS: The estrous cycles in gamma(c)
      knockout (gamma(c) KO) mice were irregular compared with wild-type mice,
      although, the mutants could become pregnant. No uterine natural killer (uNK) cell
      was found in the uterus at 13 days of pregnancy, and poor decidual formation and
      thickness of blood vessel walls were observed. Apparent differences were not seen
      in the numbers and weight of the fetuses between wild type and mutant animals,
      and fetuses were not compromised throughout pregnancy. CONCLUSIONS: The gamma(c)
      KO mice showed irregular estrous cycle but they could carry out normal pregnancy
      despite lacking uNK and cytokines actions of IL-2, 4, 7, 9 and 15.

PMID- 12069390
TI  - Differential effects of IL-11 on rat blastocysts and decidua during the peri
      implantation period.
AB  - PROBLEM: To study effects of interleukin-11 (IL-11) on blastocyst development and
      decidualization. METHOD OF STUDY: Rats, injected with buffer (C) or IL-11 [1
      mg/kg/day = high dose (HD), 60 microg/kg/week = low dose (LD)-1, 30 microg/kg
      twice a week = low dose (LD)-2] were made pregnant or pseudopregnant to obtain
      blastocysts or deciduomata. RESULTS: As compared with C, more LD-2 blastocysts
      hatched in culture, while hatching and attachment of HD blastocysts was
      decreased. Blastocysts from untreated rats in IL-11 supplemented medium (4 ng/mL)
      demonstrated increased hatching and attachment. The weight of the decidualized
      uterus in HD and LD-2 pseudopregnant rats was reduced as compared with C and LD-
      1. On deciduomata sections from IL-11 treated rats, the area inside the uterine
      muscle layer was reduced, and mitotic over pycnotic indices were increased in the
      anti-mesometrial area and decreased in the mesometrial area. CONCLUSIONS: Low
      doses of IL-11 improve hatching and attachment of blastocysts, but both high and
      low doses impair decidualization.

PMID- 12069391
TI  - Deficiency of decidual IL-10 in first trimester missed abortion: a lack of
      correlation with the decidual immune cell profile.
AB  - PROBLEM: To determine if first trimester missed abortion decidua is characterized
      by an altered immune cell profile and/or a modified interleukin (IL)-10 and
      interferon (IFN)-gamma production pattern compared with decidua from elective
      termination. METHOD OF STUDY: Flow cytometry and immunohistochemistry techniques
      were used to determine the decidual immune cell phenotypic profile and production
      pattern of IL-10 and IFN-gamma in cases of elective termination (n = 14) and
      missed abortion (n = 12). RESULTS: Both groups had a similar proportion of CD56+
      CD16-, CD56+ CD16+, CD19+, CD3+, CD4+, CD8+, alphabeta T cells and gammadelta T
      cells. The majority of alphabeta and gammadelta positive T cells in both groups
      coexpressed the natural killer (NK) cell marker CD56, but lacked cell surface
      expression of CD3. Diminished decidual IL-10 staining was noted in 7/10 missed
      abortion cases compared with none of the elective termination cases (n = 12) (P =
      0.007). A uniform decidual IFN-gamma staining pattern was observed in both
      groups. CONCLUSION: Decreased IL-10 production coupled with a sustained IFN-gamma
      presence noted in missed abortion compared with elective termination cases
      suggest that these cytokines may be important determinants in pregnancy outcome.
      In contrast, differences in the proportion of immune cells between both groups
      may not be a critical factor in early pregnancy loss. In normal pregnancy,
      decidual alphabeta and gammadelta positive T cells with reduced CD3 on their cell
      surface may be intrinsically restricted in T-cell receptor (TCR)-mediated
      activation.

PMID- 12069392
TI  - Cytokine network of eutopic and ectopic endometrium in women with adenomyosis.
AB  - PROBLEM: Recent studies showed the impairment of local cytokine balance in women
      with external endometriosis, but similar findings concerning direct production of
      cytokines by immunocompetent cells of women with adenomyosis are absent. In this
      context, investigation of the cytokine synthesis by mononuclear cells (MNCs)
      infiltrating eutopic and ectopic endometrium is of special interest. METHOD OF
      STUDY: Concentration of interferon-gamma (IFNgamma), interferon-alpha (IFNalpha),
      tumour necrosis factor-alpha (TNFalpha), interleukin- 1beta (IL-1beta) and
      epidermal growth factor (EGF) in supernatants (SNs) of 24-hr cultures of MNCs
      obtained from eutopic and ectopic endometrium of women with adenomyosis was
      determined by enzyme-linked immunosorbent assay. RESULTS: The levels of IFNgamma,
      IFNalpha, TNFalpha, IL-1beta and EGF in SNs of eutopic endometrial MNCs of women
      with adenomyosis were significantly increased and the content of IL-8 in SNs was
      reduced compared with that of the control figures. Ectopic MNCs of women with
      adenomyosis produced higher levels of IFNgamma, IFNalpha and TNFalpha than the
      MNCs of normal endometrium. The production of IL-1beta, IL-8 and EGF by ectopic
      endometrial MNCs was significantly reduced. CONCLUSION: The results obtained
      indicate a significant role of local cytokine production impairment in the
      development of adenomyosis.

PMID- 12069393
TI  - Symposium on 'dietary influences on mucosal immunity'. How dietary antigens
      access the mucosal immune system.
AB  - The intestinal epithelium is a selective barrier where incompletely-digested food
      antigens are transmitted to the immune system. Food antigens are often the
      starting point of intestinal diseases such as food allergy or coeliac disease.
      The intestinal epithelial cells (IEC) take up and process food antigens mainly by
      fluid-phase transcytosis involving two functional pathways, one minor direct
      pathway without degradation and another major lysosomal degradative pathway.
      Among the peptidic metabolites generated during transepithelial transport of
      luminal antigens, some have a molecular mass compatible with a binding to
      restriction (major histocompatibility complex; MHC) molecules; the latter can be
      up regulated on enterocytes, especially in inflammatory conditions. Indeed,
      interferon-gamma not only increases the paracellular absorption of antigens, but
      also their transcytosis across epithelial cells. It has been reported that
      enterocytes may even directly present peptidic epitopes to underlying T-cells. As
      a new potential way of transmitting peptidic information to the local or systemic
      immune system, the secretion by IEC of antigen-presenting vesicles called
      exosomes and bearing MHC-peptide complexes has recently been proposed. Many other
      factors such as nutritional or environmental factors can also influence the
      properties of the epithelial barrier and the outcome of the immune response to
      lumen antigens.

PMID- 12069394
TI  - Regulation of mucosal immune responses in effector sites.
AB  - In human disease and rodent models, immune responses in the intestinal mucosa can
      be damaging. Damage is characterised by villus atrophy, crypt hyperplasia and
      reduced ability to digest and absorb nutrients. In normal individuals active
      responses to harmless environmental antigens associated with food and commensal
      bacteria are controlled by the development of immunological tolerance. Similar
      pathological changes occur in piglets weaned early from their mothers. Active
      immune responses to food antigens are observed in these piglets, and we and
      others have hypothesised that the changes occur as a result of transient allergic
      immune responses to novel food or bacteria antigens. The normal mechanism for
      producing tolerance to food antigens may operate at induction (Peyer's patches
      and mesenteric lymph nodes) or at the effector stage (intestinal lamina propria).
      In our piglet studies immunological tolerance occurs despite the initial active
      response. Together with evidence from rodents, this observation suggests that
      active responses are likely to be controlled at the effector stage, within the
      intestinal lamina propria. Support for this mechanism comes from the observation
      that human and pig intestinal T-cells are susceptible to apoptosis, and that this
      process is accelerated by antigen. We suggest that the role of the normal mature
      intestinal lamina propria is a balance between immunological effector and
      regulatory function. In neonatal animals this balance develops slowly and is
      dependant on contact with antigen. Immunological insults such as weaning may tip
      the balance of the developing mucosal immune system into excessive effector or
      regulatory function resulting in transient or chronic allergy or disease
      susceptibility.

PMID- 12069395
TI  - Immunity induced after a feed of antigen during early life: oral tolerance v.
      sensitisation.
AB  - There is good clinical and experimental evidence that oral tolerance exists in
      man and that the timing of antigen (food) administration is an important factor
      in the development of food allergic sensitisation and disease. Induction of
      tolerance is often seen as a T-helper 2-skewed response, which on one side may
      prevent harmful mucosal immune reactions, but on the other side may contribute to
      adverse responses in the susceptible individual. The primary mechanisms by which
      tolerance may be mediated include T-cell deletion, anergy, suppression
      'ignorance' and apoptosis. Cell-mediated delayed hypersensitivity reactions (T
      helper 1), which are implicated as a pathogenetic principle in the development of
      autoimmune and gastrointestinal inflammation are particularly well suppressed.
      Regulatory events during the induction of tolerance (or sensitisation) are not
      well characterised and remain at times controversial. The balance between
      tolerance (suppression) and sensitisation (priming) is dependent on several
      factors, such as: (a) genetic background; (b) nature of antigen and dose of
      antigen; (c) frequency of administration; (d) age (maturity v. immaturity) at
      first antigen exposure; (e) immunological status of the host (e.g. virus
      infection); dietary exposure of the mother; (g) antigen transmission via breast
      milk, and others. Overall, there is evidence in rodents that multiple low-dose
      feeds are more likely to induce regulatory cytokines (e.g. transforming growth
      factor-beta, interleukins 10 and 4) in part secreted by CD4+CD25+ T-regulatory
      cells. Despite the powerful suppressive effect of oral antigen exposure observed
      in experimental models, its application in clinical trials of autoimmune diseases
      has not yet yielded the expected beneficial results.

PMID- 12069396
TI  - Nutritional factors and immune functions of gut epithelium.
AB  - The intestinal epithelium acts as a barrier to the external environment contained
      within the lumen of the gut. It also transports solutes for nutrition and for
      immunological surveillance. The present review develops the hypothesis that
      changes in diet, through the composition of the lumen environment, alter the
      expression of genes in the epithelium. These genes include those that encode for
      proteins that signal to the mucosal immune system. Directly changing the
      expression of signalling molecules in the intestinal epithelium using transgenic
      techniques alters immune function. For example, up regulation of the chemokine
      macrophage inflammatory protein-2 increases neutrophil recruitment. Furthermore,
      lumen molecules such as short-chain fatty acids regulate chemokine expression by
      epithelial cells. By this means, the epithelium acts as a transducing monolayer
      signalling between the contents of the intestine and the mucosal immune system.

PMID- 12069397
TI  - Dietary fatty acid modulation of mucosally-induced tolerogenic immune responses.
AB  - Immunological unresponsiveness or hyporesponsiveness (tolerance) can be induced
      by feeding protein antigens to naive animals. Using a classical oral ovalbumin
      gut-induced tolerance protocol in BALB/c mice we investigated the effects of
      dietary n-6 and n-3 polyunsaturated fatty acids (PUFA) on high-and low-dose oral
      tolerance (and in non-tolerised animals, i.e. effects of antigen challenge alone)
      in relation to lymphoproliferative, cytokine and antibody responses. Fish oil
      rich in long-chain n-3 fatty acids decreased both T-helper (Th) 1- and Th2-like
      responses. In contrast, borage (Borago officinalis) oil rich in n-6 PUFA, of
      which gamma-linolenic acid is rapidly metabolised to longer-chain n-6 PUFA,
      increased Thl-like responses and decreased Th2-like responses, and possibly
      enhanced suppressor cell or Th3-like activity. These findings are in general
      agreement with other studies on the effects of long chain n-3 PUFA on immune
      system functions, and characterise important differences between long-chain n-3
      and n-6 PUFA, defining more precisely and broadly the immunological regulatory
      mechanisms involved. They are also discussed in relation to autoimmune disease.

PMID- 12069399
TI  - Symposium on 'nutritional effects of new processing technologies'. New processing
      technologies: an overview.
AB  - Most food-preservation techniques act by slowing down or completely inhibiting
      the growth of micro-organisms. Few techniques act by inactivating them. While
      heat remains the technique most extensively used for inactivation, there has been
      increasing interest recently in the development of alternative approaches in
      response to the desires of consumers for products which are less organoleptically
      and nutritionally damaged during processing and less reliant on additives than
      previously. The new approaches, therefore, mostly involve technologies that offer
      full or partial alternatives to heat for the inactivation of bacteria, yeasts and
      moulds. They include the application to foods of high hydrostatic pressure, high
      voltage electric discharges, high-intensity laser and non-coherent light pulses,
      'manothermosonication' (the combination of mild heating with ultrasonication and
      slightly-raised pressure), and high-magnetic-field pulses. In addition, a number
      of naturally-occurring antimicrobials, including lysozyme and low-molecular
      weight products of micro-organisms are finding increasing use. High pressure is
      being used commercially to non-thermally pasteurize a number of foods, while the
      other physical procedures are in various stages of development and commercial
      evaluation. Possible nutritional consequences have so far been given little
      attention compared with microbiological ones.

PMID- 12069398
TI  - Modification of enteral diets in inflammatory bowel disease.
AB  - The provision of food is thought to promote the maintenance of gut integrity.
      Nutrients are able to elicit and affect both systemic and mucosal immune
      responses. Enteral diet therapy has long been known to be efficacious in
      inflammatory bowel disease (IBD), particularly in childhood Crohn's disease.
      However, the mechanisms of action of these diets are not clear. Nutritional
      repletion, direct effects on the gut mucosa or decreased intestinal permeability
      have all been postulated as being important in nutritional therapy. There is some
      evidence that the enteral diet has a direct effect on the gut mucosa by reducing
      cytokine production and the accompanying inflammation, thus leading to decreased
      intestinal permeability. Modifications of enteral diet composition have been
      evaluated in many studies. Such modifications include fat and/or protein content
      and the addition of bioactive peptides. The fatty acid composition of the enteral
      diet seems to have a much greater impact on its efficacy than modification of the
      N source. As specific fatty acids are precursors of inflammatory mediators
      derived from arachidonic acid, the reduction in these components may be
      beneficial in nutritional therapy for IBD. Addition of bioactive peptides to
      enteral diet formulas may also have a role; such peptides may have specific
      growth factor or anti-inflammatory actions. There is still much work to be done
      to define disease-specific enteral diet formulas that are effective as therapies
      for both Crohn's disease and ulcerative colitis.

PMID- 12069400
TI  - Microencapsulation: its application in nutrition.
AB  - The development of new functional foods requires technologies for incorporating
      health-promoting ingredients into food without reducing their bioavailability or
      functionality. In many cases, microencapsulation can provide the necessary
      protection for these compounds, but in all cases bioavailability should be
      carefully studied. The present paper gives an overview of the application of
      various microencapsulation technologies to nutritionally-important compounds,
      i.e. vitamins, n-3 polyunsaturated fatty acids, Ca, Fe and antioxidants. It also
      gives a view on future technologies and trends in microencapsulation technology
      for nutritional applications.

PMID- 12069401
TI  - New food components and gastrointestinal health.
AB  - Apart from its main functions of digestion, absorption and faecal processing, the
      human gastrointestinal tract has a complex pattern of muscular activity regulated
      by a largely autonomous nervous system, and its various organs contain large
      concentrations of immune and endocrine tissues. Any failure of these closely
      integrated systems can lead to diseases ranging from the mildly irritating to the
      life threatening. Food contains a huge variety of chemical species, many of which
      are biologically active, and the distal regions of the gut are colonised by a
      rich and metabolically-active commensal flora that depend on nutrients derived
      ultimately from the host's dietary residues. The present paper explores the
      evidence for significant effects of food ingredients on functional bowel
      disorders, intestinal infections, and aspects of epithelial cell physiology
      involved in the development of colo-rectal neoplasia. Various strategies,
      including the manipulation of the colo-rectal microflora with pre- and
      probiotics, and the development of new products and plant varieties containing
      biologically-active constituents, have the potential to underpin the development
      of novel functional food products. However, these products will need to be based
      on proven biological principles, and fully tested for efficacy and safety. The
      rapidly-developing fields of functional genomics and cell biology will open up
      new experimental strategies to explore these possibilities, and emerging
      processing technologies seem likely to provide novel methods for their
      exploitation.

PMID- 12069402
TI  - Technical constraints in the development of reduced-fat bakery products.
AB  - The present study was funded by the Ministry of Agriculture, Fisheries and Food,
      its aim being to identify the technical barriers to the development of reduced
      fat alternatives for bakery products. Using National Food Survey (Ministry of
      Agriculture, Fisheries and Food, 1998) statistics on dietary consumption within
      the home, biscuits, cakes and pastries were identified as contributing
      significant amounts of fat to the population's dietary intake. Face-to-face
      interviews were conducted with contacts in the technical community of the baking
      industry, who were usually working in technical and new-product development
      functions. A discussion guide was developed to cover the main lines of enquiry.
      The companies selected were ingredient suppliers (eight), manufacturers (twelve)
      and retailers (four) and so represented each step of the food supply chain. In
      brief, results showed that current labelling rules were too stringent, and
      constrained development of reduced-fat bakery products. Products with lower fat
      levels are harder to make due to altered handling and processing properties.
      Their quality is usually poorer than standard products, particularly for flavour,
      texture and mouthfeel. The perception of freshness is reduced and product shelf
      life may consequently be shorter. For the product developer, there are relatively
      few ingredients that can be used in place of fat, and knowledge of how they work
      is limited, which inhibits product development. There is no identifiable source
      of technical knowledge in this field. Consumers perceive reduced-fat bakery
      products to be of lower quality and are generally unwilling to pay higher prices
      than for standard products.

PMID- 12069403
TI  - Symposium on 'nutritional adaptation to pregnancy and lactation'. Pregnancy as a
      time for dietary change?
AB  - It is thought that nutrition during pregnancy plays a key role in the well-being
      of the mother and the newborn infant, and further influences health during
      childhood and adulthood. Pregnancy is a time of increased nutritional
      requirements, but many of these requirements will be met by adaptive
      physiological changes that occur during gestation, with little need to alter
      maternal dietary intake. A modest increment of food which provides 0.8 MJ/d
      (above prepregnant requirements) during the third trimester is considered
      adequate to meet the needs of fetal and maternal growth, and to satisfy the small
      increase in requirements of many macro- and micronutrients. However, requirements
      for vitamin D and folic acid increase substantially, and should be met primarily
      by supplementation. Food selection may also be altered to avoid a range of food
      borne diseases and toxic constituents. There are a number of psycho-social
      reasons why pregnancy might be considered a good time for promoting changes in
      dietary behaviour for the health of the wider family. However, pregnancy may be a
      bad time to promote dietary change if it is perceived to involve slimming, if
      nutritional requirements are greatest before pregnancy, or if dietary changes
      made are harmful. There is little evidence to support educational interventions
      as successful at changing dietary behaviour during pregnancy. Pregnancy may be
      best viewed as an opportunity for maintaining good dietary selections and for
      building knowledge for future action, and should not be seen as the only
      opportunity for promoting dietary change within the life course.

PMID- 12069404
TI  - Fetal programming of cardiovascular function through exposure to maternal
      undernutrition.
AB  - A substantial and robust body of epidemiological evidence indicates that prenatal
      dietary experience may be a factor determining cardiovascular disease risk.
      Retrospective cohort studies indicate that low birth weight and disproportion at
      birth are powerful predictors of later disease risk. This prenatal influence on
      non-communicable disease in later life has been termed programming. Maternal
      nutritional status has been proposed to be the major programming influence on the
      developing fetus. The evidence from epidemiological studies of nutrition, fetal
      development and birth outcome is, however, often weak and inconclusive. The
      validity of the nutritional programming concept is highly dependent on
      experimental studies in animals. The feeding of low-protein diets in rat
      pregnancy results in perturbations in fetal growth and dimensions at birth. The
      offspring of rats fed low-protein diets exhibit a number of metabolic and
      physiological disturbances, and are consistently found to have high blood
      pressure from early postnatal life. This experimental model has been used to
      explore potential mechanisms of programming through which maternal diet may
      programme the cardiovascular function of the fetus. Indications from this work
      are that fetal exposure to maternally-derived glucocorticoids plays a key role in
      the programming mechanism. Secondary to this activity, the fetal hypothalamic
      pituitary-adrenal axis may stimulate renin-angiotensin system activity, resulting
      in increased vascular resistance and hypertension.

PMID- 12069405
TI  - Nutrient partitioning between reproductive and immune functions in animals.
AB  - The physiological processes that underlie the reproductive cycle impose
      considerable metabolisable protein (MP) demands on a female, especially during
      the periparturient period. When MP supply falls short of MP demand (i.e. MP
      becomes scarce), certain, if not all, bodily functions are expected to be
      penalised. It has been proposed that partitioning of scarce MP is prioritised to
      reproductive rather than to immune functions. In other words, at times of MP
      scarcity, the penalty on expression of immunity would be expected to be greater
      than that on reproduction. This hypothesis forms a nutritional basis for the
      occurrence of periparturient breakdown of immunity to parasites (BIP), which can
      be observed in many host-parasite systems. In the present review we explore this
      nutritional basis, using periparturient sheep infected with the abomasal nematode
      Teladorsagia circumcincta as an example, and attempt to quantify its occurrence.
      Evidence supporting the nutritional basis of periparturient BIP is reviewed,
      covering experiments in which nutrient supply (from both exogenous and endogenous
      sources) and/or nutrient demand were manipulated. Quantitatively, MP requirements
      for expression of immunity to T. circumcincta were estimated to be about 1 g/kg
      metabolic body weight (body weight 0.75) per d, approximately 5% of the maximum
      MP requirements of periparturient sheep. The major component of this requirement
      was assumed to be for replenishing irreversible plasma protein losses into the
      gastrointestinal tract. Although confirmation of this estimate is required, such
      estimates may be used to improve the known MP requirements of periparturient
      animals, enabling the extent and the consequences of periparturient BIP to be
      minimised.

PMID- 12069406
TI  - Lactation and gestation in dairy cows: flexibility avoids nutritional extremes.
AB  - The modern dairy cow has been selectively bred to produce large amounts of milk.
      Partly as a result, food consumption is considerably less than milk energy output
      in early lactation. It is only at 2 months or more postpartum that intake
      increases to the point where positive energy balance is regained, the initial
      production being achieved by a substantial mobilisation of body reserves. These
      reserves are laid down before parturition, but it is certainly not the case that
      the pregnant cow will accumulate adipose tissue recklessly; in the last third of
      pregnancy well-fed cows in good body condition exhibit reduced, not increased,
      appetite. There is a fine balancing act to perform. Excessive body condition at
      parturition quickly leads to metabolic problems such as ketosis, but cows who
      subsequently become too thin have increased risk of metabolic diseases such as
      mastitis and lameness. The biological mechanisms regulating output of milk are
      reasonably well understood, those controlling appetite less well so, and there
      has been little attempt at systematic integration of the two. The transition from
      pregnancy to lactation represents a major challenge to homeostasis, made more
      complicated in multiparous cows by the fact that much of gestation is concurrent
      with lactation. Herein lies the potential for nutritionally-entrained
      flexibility. In the wild, concurrent pregnancy and lactation only occur when
      nutritional conditions are favourable. If conditions are poor, rebreeding will be
      delayed and lactation will continue, at an energetically-sustainable level, for
      much longer than its 'normal' duration. In this way the twin energetic burdens of
      pregnancy and lactation are separated, and extremes are avoided. Given the
      increasing public concern about stresses suffered by intensively-managed dairy
      cows, this case may be one where commercial dairying could learn useful lessons
      from nature.

PMID- 12069408
TI  - Development of a fluorescence polarization assay for peptidyl-tRNA hydrolase.
AB  - Peptidyl-tRNA hydrolase (Pth) activity ensures the rapid recycling of peptidyl
      tRNAs that result from premature termination of translation. Historically, the
      hydrolyzing activity of Pth has been assayed with radiolabeled N-blocked
      aminoacyl-tRNAs in assay systems that require the separation of radiolabeled
      amino acid from the N-blocked aminoacyl-tRNA complex. In the present study, we
      describe the development of a kinetic fluorescence polarization (FP) assay that
      enables measurements of Pth activity without the need to separate bound and free
      tracer. The hydrolyzing activity of Pth was determined by measuring the change in
      polarization values that resulted from the cleavage of a fluorescently labeled
      substrate (BODIPY-Lys-tRNA(Lys)). The data were analyzed using an equation
      describing first-order dissociation and the results showed that the experimental
      data correlated well with the theoretical curve. A runs test of the residuals
      showed that the experimental data did not significantly differ from the first
      order model. The assay is adaptable to a multiwell format and is sensitive enough
      to detect Pth-like activity in bacterial cell lysate. The Pth FP assay provides a
      homogeneous and kinetic format for measuring Pth activity in vitro.

PMID- 12069407
TI  - Cytokinin oxidase/cytokinin dehydrogenase assay: optimized procedures and
      applications.
AB  - Spectrophotometric methods for determining the activity of cytokinin
      oxidase/cytokinin dehydrogenase (EC 1.5.99.12) were developed and optimized. A
      sensitive end-point method based on a combination of the electron acceptor 2,6
      dichlorophenolindophenol and Schiff base formation of the reaction product with 4
      aminophenol under acidic conditions can be applied to crude cell and tissue
      extracts. The assay was also adapted for other substrates than N6-(2
      isopentenyl)adenine, such as zeatin and the aromatic cytokinins, although an
      enzyme which degrades the latter compounds has not yet been identified. The
      second novel method is an initial rate method based on the coupled redox reaction
      of phenazine methosulfate and 3-(4,5-dimethylthiazol-2-yl)-2,5-
      diphenyltetrazolium bromide resulting in the formation of a formazan dye. This
      method can be used for kinetic studies with purified enzyme and is entirely
      substrate independent.

PMID- 12069409
TI  - A multitarget assay for inhibitors of membrane-associated steps of peptidoglycan
      biosynthesis.
AB  - Peptidoglycan synthesis begins in the cytoplasm with the condensation of UDP-N
      acetyl glucosamine (UDP-GlcNAc) and phosphoenolpyruvate catalyzed by UDP-N
      acetylglucosamine enolpyruvoyl transferase. UDP-GlcNAc is also utilized as
      substrate for the glycosyltransferase MurG, a membrane-bound enzyme that
      catalyzes the production of lipid II. Membranes from Escherichia coli cells
      overproducing MurG support peptidoglycan formation at a rate approximately
      fivefold faster than membranes containing wild-type levels of MurG. Conditions
      have been optimized for the production of large amounts of membranes with
      increased levels of MurG, allowing the development of an assay suitable for high
      throughput screening of large compound libraries. The quality of the purified
      membranes was assessed by electron microscopy and also by testing cross-linked
      peptidoglycan production. Moreover, kinetic studies allowed the determination of
      optimal concentrations of the substrates and membranes to be utilized for maximum
      sensitivity of the assay. Using a 96-well assay format, the IC50 values for
      vancomycin, tunicamycin, flavomycin, and bacitracin were 1.1 microM, 0.01
      microg/ml, 0.03 microg/ml, and 0.7 microg/ml, respectively.

PMID- 12069410
TI  - Monitoring and kinetic parameter estimation for the binding process of berberine
      hydrochloride to bovine serum albumin with piezoelectric quartz crystal impedance
      analysis.
AB  - A new method for monitoring, in real time, the drug-binding process to protein
      with piezoelectric quartz crystal impedance (PQCI) is proposed. The method was
      used to monitor the binding process of berberine hydrochloride to bovine serum
      albumin (BSA). BSA was immobilized on the silver electrode surface of a
      piezoelectric quartz crystal and the optimized experimental conditions were
      established. The BSA-coated piezoelectric sensor was in contact with berberine
      solution. The time courses of the resonant frequency and equivalent circuit
      parameters of the sensor during the protein-drug binding were simultaneously
      obtained. On the basis of the analysis of the multidimensional information
      provided by PQCI, it was concluded that the observed frequency decrease was
      mainly ascribed to the mass increase of the sensor surface resulting from the
      binding. According to the frequency decrease with time, the kinetics of the
      binding process were quantitatively studied. A piezoelectric response model for
      the binding was theoretically derived. Fitting the experimental data to the
      model, the kinetic parameters, such as the binding and dissociation rate
      constants (k(1) and k(-1)) and the binding equilibrium constant (K(a)), were
      determined. The k(1), k(-1), and K(a) values obtained at 25 degrees C were 67.5
      (+/-0.1) (mol liter(-1))(-1) s(-1), 1.7 (+/- 0.1) x 10(-3) s(-1), and 3.97 (+/-
      0.06) x10(4) (mol liter(-1))(-1), respectively.

PMID- 12069411
TI  - A liquid chromatographic-electrospray ionization-tandem mass spectrometric method
      for determination of buprenorphine, its metabolite, norbuprenorphine, and a
      coformulant, naloxone, that is suitable for in vivo and in vitro metabolism
      studies.
AB  - A liquid chromatographic-electrospray ionization-tandem mass spectrometric method
      has been developed and validated for determination of the antiabuse medication,
      buprenorphine, its primary metabolite, norbuprenorphine, and a proposed
      coformulant, naloxone. The method uses deuterated internal standards and a simple
      liquid-liquid extraction. Mass spectrometry employed selected reaction monitoring
      of the transitions of m/z 468 to 396 for buprenorphine, 472 to 400 for
      [2H4]buprenorphine, 414 to 101 for norbuprenorphine, 423 to 110 for
      [2H9]norbuprenorphine, 328 to 310 for naloxone, and 345 to 327 for its internal
      standard, [2H3]naltrexone. The method was accurate and precise across the dynamic
      range of 0.1 to 10 ng/ml. All analytes were stable in human plasma stored at room
      temperature for up to 24 h and after three freeze-thaw cycles. Reconstituted
      extracts were stable at -20 degrees C for up to 3 days. In human subjects
      receiving a sublingual tablet of 8 mg buprenorphine and 2 mg naloxone,
      buprenorphine and norbuprenorphine were detected for up to 24 h with respective
      maximum concentrations at 1 and 1.5 h. Maximal concentrations ranged from 2.2 to
      2.8 and 1.5 to 2.4 ng/ml for buprenorphine and norbuprenorphine, respectively
      (i.e., approximately 6 nM). The method detected norbuprenorphine formation in
      human liver microsomes incubated with 5-82 nM buprenorphine, which encompasses
      the therapeutic plasma concentration range. When cDNA-expressed P450s were
      incubated with 21 nM buprenorphine, norbuprenorphine formation was detected for
      P450s 3A4, as previously described, but also for 3A5, 3A7, and 2C8. Buprenorphine
      utilization generally exceeded norbuprenorphine formation, suggesting that P450s
      2C18, 2C19, 2D6, and 2E1 may also be involved in buprenorphine metabolism to
      other products. These results suggest this method is suitable for both in vivo
      and in vitro studies of buprenorphine metabolism to norbuprenorphine.

PMID- 12069412
TI  - An in vitro hydroxyl radical generation assay for microdialysis sampling
      calibration.
AB  - A xanthine oxidase hydroxyl radical (.OH)-generating system was created for
      sustained in vitro production of *OH. This assay was coupled with microdialysis
      sampling to elucidate the factors that influence microdialysis calibration during
      radical trapping. A *OH trapping agent, 4-hydroxybenzoic acid, was included
      either in the microdialysis perfusion fluid or in the medium external to the
      microdialysis probe. Xanthine oxidase enzymatic activity was reproducible and had
      an average activity measured by UV absorbance of produced uric acid of 0.037 +/-
      0.005 deltaAU/min (n = 5). A considerable amount of variance in the rate and
      amount of the product, 3,4-dihydroxybenzoic acid (3,4-DHBA), was observed when
      one microdialysis probe was placed in the reaction mixture. When two
      microdialysis probes were placed in the reaction mixture, a greater rate and
      amount of 3,4-DHBA was observed. Different concentrations of 3,4-DHBA were
      obtained between quiescent and stirred systems.

PMID- 12069413
TI  - Protein microarrays to detect protein-protein interactions using red and green
      fluorescent proteins.
AB  - Proteomics, the study of protein function on a global scale, will play an
      important role in furthering our understanding of gene functions, complex
      biological pathways, and discovery of novel drug targets. A number of techniques
      have been developed for proteomic studies to identify and analyze proteins,
      compare protein expression levels, and study protein-protein interactions. Recent
      developments have applied a DNA array-type approach to immobilize proteins on a
      surface for high-throughput analysis. Here we report the development and
      construction of protein chips using derivatized glass and nitrocellulose-coated
      slides and the employment of recombinant proteins fused with green and red
      fluorescent proteins for detection. Fluorescent signals were found to be
      proportional to the amount of arrayed proteins and could be readily detected with
      a conventional fluorescence slide scanner. This technique allows the
      investigation of protein-protein interactions without the need for additional
      labeling steps of probe proteins.

PMID- 12069414
TI  - A comparison of hydraulic and laser capture microdissection methods for
      collection of single B cells, PCR, and sequencing of antibody VDJ.
AB  - During the development of B lymphocytes, a series of gene rearrangements assemble
      the sequences that encode immunoglobulin heavy and light chains (VDJ). Earlier
      studies of VDJ sequence diversification during expansion of cells in splenic or
      appendix germinal centers used hydraulic micromanipulation (HM) to collect single
      B cells for PCR amplification of rearranged antibody heavy and light chain genes.
      PCR products were directly sequenced without a cloning step. Hydraulic
      micromanipulation is a very tedious method. Once capability to collect single
      cells by laser capture microdissection (LCM) was developed, we modified previous
      tissue staining and fixation methods so that we could collect cells from a given
      stained tissue section by HM and LCM and directly compare our success rates using
      these two methods. Cells were alkaline lysed and after two rounds of nested PCR
      products were recovered and directly sequenced. Because each rearrangement of
      genomic DNA that occurs to form the immunoglobulin heavy-chain-encoding sequence
      in developing B cells is unique, this system allowed us to verify our success
      rate in recovering single lymphocytes from tissue sections and amplifying a
      single allele. The methods developed have now made LCM an efficient alternative
      to HM for the collection of single B cells.

PMID- 12069415
TI  - A high-throughput denaturing high-performance liquid chromatography method for
      the identification of variant alleles associated with dihydropyrimidine
      dehydrogenase deficiency.
AB  - Dihydropyrimidine dehydrogenase (DPD) is the initial, rate-limiting enzyme in the
      catabolism of 5-fluorouracil (5-FU). A pharmacogenetic syndrome has been
      described in which DPD-deficient patients are at risk for toxicity following
      administration of 5-FU. To date, there are at least 21 previously described
      mutations and/or polymorphisms that have been associated with DPD deficiency. In
      this study we describe the development of a highly specific, sensitive,
      inexpensive, and robust denaturing HPLC (DHPLC) method for rapidly identifying
      sequence variations (mutations and/or polymorphisms) in the gene (DPYD) that
      codes for the DPD enzyme. DHPLC conditions were optimized at three temperatures
      for analysis of the 23 exons of the DPYD gene using 25 amplicons representing the
      entire coding sequence, including all intron/exon boundaries (splice sites).
      Resolution of all 25 amplicons at the optimized temperature can be performed in
      4.2 h. All 21 previously described sequence variations (mutations and/or
      polymorphisms) were prepared using site-directed mutagenesis from the wild-type
      DPYD gene, confirmed by sequence analysis, and subsequently resolved by DHPLC
      using the optimized conditions. These analyses generated reference chromatogram
      patterns for all known sequence variations previously encountered in DPD
      deficient patients. In order to examine the utility and sensitivity of this
      approach, samples from patients with known sequence variations in the DPYD gene
      were analyzed. This DHPLC technique resolved 100% of the known DPYD sequence
      variations and differentiated between homozygous and heterozygous genotypes. We
      conclude that this DHPLC method is a highly specific and sensitive technique for
      rapidly detecting known sequence variations in the DPYD gene. In addition, this
      approach can be used to identify currently unrecognized unknown sequence
      variations in the DPYD gene and should be useful in future pharmacogenetic
      studies examining DPD deficiency.

PMID- 12069416
TI  - Introduction of functional groups onto polypropylene and polyethylene surfaces
      for immobilization of enzymes.
AB  - Polypropylene and polyethylene surfaces are activated by introducing an active
      functional group through 1-fluoro-2 nitro-4-azidobenzene by UV irradiation.
      Horseradish peroxidase and glucose oxidase are immobilized onto the activated
      surfaces, simply by incubating the enzymes at 37 degrees C. When untreated
      surfaces are used, insignificant immobilization of the enzymes is observed.

PMID- 12069417
TI  - Spectrophotometric determination of serum nitrite and nitrate by copper-cadmium
      alloy.
AB  - A macro and micro assay for the spectrophotometric determination of serum nitrite
      and nitrate was developed. Nitrite/nitrate in biological samples can be estimated
      in a single step by this method. The principle of the assay is the reduction of
      nitrate by copper-cadmium alloy, followed by color development with Griess
      reagent (sulfanilamide and N-naphthylethylenediamine) in acidic medium. This
      assay is sensitive to 1 microM nitrate and is suitable for different biological
      fluids, including sera with a high lipid concentration. The copper-cadmium alloy
      used in the present method is easy to prepare and can completely reduce nitrate
      to nitrite in an hour. The present method provides a simple, cost-effective assay
      for the estimation of stable oxidation products of nitric oxide in biological
      samples.

PMID- 12069418
TI  - Intact glucosinolate analysis in plant extracts by programmed cone voltage
      electrospray LC/MS: performance and comparison with LC/MS/MS methods.
AB  - We present a comprehensive, sensitive, and highly specific negative ion
      electrospray LC/MS method for identifying all structural classes of
      glucosinolates in crude plant extracts. The technique is based on the observation
      of simultaneous maxima in the abundances of the m/z 96 and 97 ions, generated by
      programmed cone voltage fragmentation, in the mass chromatogram. The abundance
      ratios lie in the range 1:2-1:4 ([m/z 96]/[m/z 97]). Examination of the
      corresponding full-scan mass spectra allows individual glucosinolates of all
      structural classes to be identified rapidly and with confidence. The use of
      linearly programmed cone voltage fragmentation enhances characteristic fragment
      ions without compromising the abundance of the analytically important [M - H]-
      ion and its associated (and analytically useful) sulfur isotope peaks. Detection
      limits are in the low nanogram range for full-scan, programmed cone voltage
      spectra. Comparison of the technique with LC/MS/MS methods (product ion,
      precursor ion, and constant neutral loss scans) has shown that the sensitivity
      and selectivity of the programmed cone voltage method is superior. Data obtained
      on a variety of plant extracts confirmed that the methodology was robust and
      reliable.

PMID- 12069419
TI  - Separation of synthetic oligonucleotide dithioates from monothiophosphate
      impurities by anion-exchange chromatography on a mono-q column.
AB  - A method using a strong anion-exchange liquid-chromatography column, Mono-Q, has
      been developed for high-resolution analysis and purification of oligonucleotide
      dithioates, which were synthesized by an automated, solid-phase,
      phosphorothioamidite chemistry. High-resolution separation of oligonucleotide
      phosphorodithioates from monothiophosphate impurities was obtained. High
      resolution separation was also demonstrated at pH 8. The separation of
      oligonucleotide dithioates was found to be linearly dependent on the number of
      sulfurs for the same sequence length. Thiocyanate, SCN-, as eluting anion, can be
      used to purify oligonucleotides containing a high percentage of
      phosphorodithioate linkages in lower salt concentrations and provides better
      separation than chloride as eluting anion.

PMID- 12069420
TI  - Fluorescence assay for the binding of ribonuclease A to the ribonuclease
      inhibitor protein.
AB  - Ribonuclease A (RNase A) and the ribonuclease inhibitor protein (RI) form one of
      the tightest known protein-protein complexes. RNase A variants and homologues,
      such as G88R RNase A, that retain ribonucleolytic activity in the presence of RI
      are toxic to cancer cells. Herein, a new and facile assay is described for
      measuring the equilibrium dissociation constant (K(d)) and dissociation rate
      constant (k(d)) for complexes of RI and RNase A. This assay is based on the
      decrease in fluorescence intensity that occurs when a fluorescein-labeled RNase A
      binds to RI. To allow time for equilibration, the assay is most readily applied
      to those complexes with K(d) values in the nanomolar range or higher. Using this
      assay, the value of K(d) for the complex of RI with fluorescein-labeled G88R
      RNase A was determined to be 0.55 +/- 0.03 nM. In addition, the value of K(d) was
      determined for the complex of RI with unlabeled G88R RNase A to be 0.57 +/- 0.05
      nM by using a competition assay with fluorescein-labeled G88R RNase A. Finally,
      the value of k(d) for the complex of RI with fluorescein-labeled G88R RNase A was
      determined to be (7.5 +/- 0.4) x 10(-3) s(-1) by monitoring the increase in
      fluorescence intensity upon dissociation. This assay can be used to characterize
      complexes of RI with a wide variety of RNase A variants and homologues, including
      those with cytotoxic activity.

PMID- 12069421
TI  - The other Topa: formation of 3,4,5-trihydroxyphenylalanine in peptides.
AB  - Hydroxylation of peptidyl-3,4-dihydroxyphenyl-l-alanine (Dopa) was observed
      during tyrosinase incubation of a decapeptide related to the mussel adhesive
      protein mefp1. The reaction was carried out at high enzyme concentrations (700
      units tyrosinase/micromol of tyrosine). The hydroxylation of tyrosines in the
      decapeptide proceeds sequentially. First, Tyr-9 is hydroxylated to Dopa, followed
      by hydroxylation of Tyr-5; finally, Dopa-9 is hydroxylated to Topa. Topa was
      identified as 3,4,5-trihydroxyphenylalanine (3,4,5-Topa) by comparison to known
      standards using amino acid analysis, derivatization with phenylisothiocyanate in
      combination with Edman sequencing, and matrix-assisted laser desorption mass
      spectrometry with time-of-flight. Two other peptides, not related to mussel
      proteins, were also found to form peptidyl-Topa upon incubation with tyrosinase.
      Although 3,4,5-Topa has been reported in the primary sequence of several
      peptides, its formation in vitro from tyrosine-containing peptides is novel. The
      formation of Topa would appear to be a function of tyrosinase rather than the
      nucleophilic addition of water to dopaquinone.

PMID- 12069422
TI  - A fluorescence-based, high-throughput sphingomyelin assay for the analysis of
      Niemann-Pick disease and other disorders of sphingomyelin metabolism.
AB  - Sphingomyelin is an important lipid component of cell membranes and lipoproteins
      that can be hydrolyzed by sphingomyelinases into ceramide and phosphorylcholine.
      The Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders
      due to the deficient activity of the enzyme acid sphingomyelinase and the
      resultant accumulation of sphingomyelin in cells, tissues, and fluids. In this
      paper we report a new, enzymatic method to quantify the levels of sphingomyelin
      in plasma, urine, or tissues from NPD patients and mice. In this assay, bacterial
      sphingomyelinase is first used to hydrolyze sphingomyelin to phosphorylcholine
      and ceramide. Alkaline phosphatase then generates choline from the
      phosphorylcholine, and the newly formed choline is then used to generate hydrogen
      peroxide in a reaction catalyzed by choline oxidase. Finally, with peroxidase as
      a catalyst, hydrogen peroxide reacts with the Amplex Red reagent to generate a
      highly fluorescent product, resorufin. These enzymatic reactions are carried out
      simultaneously in a single 100-microl reaction mixture for 20 min. Use of a 96
      well microtiter plate permits automated and sensitive quantification using a
      plate reader and fluorescence detector. This procedure allowed quantification of
      sphingomyelin over a broad range from 0.02 to 10 nmol, similar in sensitivity to
      a recently described radioactive method using diacylglycerol kinase and 50 times
      more sensitive than a colorimetric, aminoantipyrine/phenol-based assay. To
      validate this new assay method, we quantified sphingomyelin in plasma, urine, and
      tissues from normal individuals and from NPD mice and patients. The sphingomyelin
      content in adult homozygous or heterozygous NPD mouse plasma and urine was
      significantly elevated compared to that of normal mice. Moreover, the accumulated
      sphingomyelin in the tissues of NPD mice was 4 to 15 times higher than that in
      normal mice depending on the tissue analyzed. The sphingomyelin levels in plasma
      from several Type B NPD patients also was significantly elevated compared to
      normal individuals of the same age. Based on these results, we propose that this
      new, fluorescence-based procedure can provide simple, fast, sensitive, and
      reproducible sphingomyelin quantification in tissues and fluids from normal
      individuals and NPD patients. It could also be a useful tool for the study of
      other sphingomyelin-related diseases and in a variety of research settings where
      sphingomyelin quantification is required.

PMID- 12069423
TI  - Synthesis and characterization of a collagen model delta-O-phosphohydroxylysine
      containing peptide.
AB  - The existence of delta-O-phosphohydroxylysine (HylP) residues in collagen has
      been reported. However, such phosphorylated residues have not been isolated nor
      has their location within the protein sequence been identified. To develop the
      analytical chemistry necessary for the identification of HylP in proteins, a
      model HylP-containing peptide, Phe-dl-HylP-Gly-Gln-Pro-Ala-Ile-Gly-Phe (I), was
      synthesized. The peptide was assembled using 9-fluorenylmethyloxycarbonyl (Fmoc)
      based solid-phase synthesis; N(alpha)-Fmoc-dl-hydroxy-dl-Lys(N(epsilon)-tert
      butyloxycarbonyl)-OH was used to incorporate Hyl, and global
      phosphitylation/oxidation was used to introduce the phosphate group. The pK(a2)
      of the phosphate group, as determined using 31P NMR, was 5.6. Phosphoamino acid
      analysis of I was performed using either dabsyl chloride or phenylisothiocyanate
      derivatization followed by microbore reversed-phase HPLC separation of N(alpha,
      epsilon)-didabsyl-HylP or N(alpha, epsilon)-diphenylthiocarbamyl-HylP. HylP was
      found to be relatively resistant to acid hydrolysis, allowing for its
      quantitation. Solid-phase Edman degradation of I was used for positive
      identification of N(alpha)-phenylthiohydantoin-N(epsilon)-phenylthiocarbamyl
      HylP. The masses of the phenylthiohydantoin and dabsyl derivatives of HylP were
      confirmed by electrospray ionization triple-quadrupole (ESI-MS). Peptide I was
      positively identified as a phosphopeptide by ESI-MS/precursor-ion scanning. Low
      energy ESI-MS/MS confirmed the position of HylP within the sequence of I.
      Phosphorylation of Hyl led to complete resistance of I to lysine-specific
      endopeptidases.

PMID- 12069424
TI  - Identification and quantification of protecting groups remaining in commercial
      oligonucleotide products using monoclonal antibodies.
AB  - Quality control is paramount to reproducibly achieving oligonucleotide
      therapeutics and diagnostics of superior value. However, incomplete deprotection
      of nucleoside reactive groups after the automated chemical synthesis of
      oligonucleotides would result in diminished antisense activity and in erroneous
      array analysis of gene expression. Mass spectrometry and capillary
      electrophoresis are used to detect aborted sequences of oligonucleotides, but not
      to identify and quantify incompletely deprotected oligonucleotides. To address
      this problem, monoclonal antibodies (MAbs), ELISA, and dot-blot assays were
      developed for the specific identification and quantification of the commonly used
      nucleic acid base- and sugar-protecting groups: benzoyl, isobutyryl,
      isopropylphenoxyacetyl, and dimethoxytrityl. Each MAb was capable of reproducibly
      detecting 8-32 pmol of the respectively protected nucleoside in an intact DNA or
      RNA sample composed of 320-640 nmol of the deprotected nucleoside. In a direct
      comparison, HPLC nucleoside composition analysis of enzyme-hydrolyzed DNA was
      limited to the detection of 2-5 nmol of protected nucleoside. Using the MAb dot
      blot assay, 5 of 16 commercial DNA products obtained from eight different
      companies were found to have 1.0-5.2% of the benzoyl and isopropylphenoxyacetyl
      protecting groups remaining. Thus, MAbs selectively identify and quantify
      picomoles of remaining protecting groups on antisense therapeutics and
      oligonucleotide diagnostics.

PMID- 12069425
TI  - Activity of phospholipase C in two-phase systems.
AB  - Although phospholipase C (PLC) is known to be activated by water-insoluble
      organic solvents, most activity assays have been designed to work in an aqueous
      milieu. Here a sensitive method is described for the determination of PLC
      activity in two-phase systems. The assay is based on the hydrolysis of
      phosphatidylcholine (PC) in chloroform/buffer. The initial rates of the reaction
      are determined by densitometric quantification of the product 1,2-diacylglycerol
      after its separation by high-performance TLC and staining with a CuSO4/H3PO4 or p
      methoxybenzaldehyde/H2SO4 reagent. The method is examined for the determination
      of Vmax and Km values of PCs with varying length acyl chains (C10-C18). The
      comparison of the kinetic parameters with the Vmax and Km values of the same
      substrates in the conventional titrimetric assay, using sodium deoxycholate for
      micellization of PC, demonstrates the high efficiency of PLC in the two-phase
      emulsion system.

PMID- 12069426
TI  - Reducing the cost of consumables used for ABI 310 genetic analyzer.

PMID- 12069427
TI  - Stability of oxygen deprivation in glass culture vessels facilitates fast
      reproducible cell death to cortical neurons under simulated ischemia.

PMID- 12069428
TI  - Enhanced detection of chemiluminescence intensity during an oxidative burst
      reaction in suspension cultured Nicotiana tabacum cells through the use of
      Ficoll.

PMID- 12069429
TI  - A new approach for efficient directional genome walking using polymerase chain
      reaction.

PMID- 12069430
TI  - pH corrections in chemical denaturant solutions.

PMID- 12069431
TI  - Engagement in community service among college students: is it affected by
      significant attachment relationships?
AB  - This study served as an exploratory analysis of how engagement in community
      service activities among college students is affected by significant attachment
      relationships. More specifically, this study investigated the difference between
      community service and non-service students in terms of their motivation to engage
      in community service activities as a function of the quality of their attachment
      to parents and close personal friends. A quantitative approach was used to
      analyse these issues. The findings revealed that students who had some community
      service experience evidenced more secure attachments to close personal friends
      while their attachments to parents were varied. Closer examination of the
      attachment data revealed that the community service students were more likely to
      have either very high or very low attachment relationships with their parents.
      These findings suggest that when incorporating service-learning into the college
      curriculum, one should examine the influence of other important contexts, (i.e.
      parents and peers) on community service outcomes.

PMID- 12069432
TI  - Do juveniles bully more than young offenders?
AB  - This study compares bullying behaviour among juvenile and young offenders and
      incorporates two different methods to measure bullying. Ninety-five male juvenile
      and 196 male young offenders completed two questionnaires, one that measured
      bullying directly and one that measured behaviours indicative of "being bullied"
      or of "bullying others". Juveniles perceived a higher extent of bullying than
      young offenders. Juveniles reported significantly more physical, psychological or
      verbal and overall direct forms of bullying behaviour than young offenders. A
      number of differences were found between juveniles and young offenders with
      regard to the types of prisoners likely to become victims, who they would advise
      a victim to speak to and how bullying could be prevented. The results are
      discussed in relation to developmental theories of aggression and how bullying
      behaviour can be defined and measured among prisoners.

PMID- 12069433
TI  - Adolescents' beliefs about future substance use: a comparison of current users
      and non-users of cigarettes, alcohol and illicit drugs.
AB  - OBJECTIVES: To explore the expectations of adolescents about their future
      cigarette, alcohol and illicit drug use. It was hypothesized that differences
      would be found between current substance users and non-users and that younger
      children would have less realistic beliefs about their future use than older
      children. DESIGN, SETTING, PARTICIPANTS: Survey of 7022 pupils (aged 11-16) in 13
      non-randomly selected schools from three Local Education Authority areas in
      Northern England, the Midlands and London, relating to current substance use and
      beliefs about future use of cigarettes, alcohol and illicit drugs. MEASURES:
      Respondents were asked confidentially about occasions of cigarette, alcohol and
      illicit drugs use as well as about their belief about use in the year following
      the survey. RESULTS: Substantial differences were found in relation to all
      substances. Of those children who currently smoked, 73% believed it likely they
      would be doing so in a year's time. Only 3% of non-smokers believed they would
      begin to smoke in the year following the survey. Eighty-three per cent of alcohol
      drinkers believed they would be drinking in a year's time compared with 20% of
      non-drinkers and 63% of illicit drug users believed in their continued use. Only
      3% of non-drug users believed they would initiate use in the year following the
      survey. More non-smoking girls than boys responded "don't know" when asked about
      their future beliefs regarding cigarette use (15.6% vs. 11.3%), a position which
      was reversed for current smokers (15.4% vs. 19.3%). 13.1% of drinkers and 30.7%
      of non-drinkers did not know if they would be drinking a year after the survey
      and 23.2% of illicit drug users did not know what their drug using status would
      be in a year compared to 9.7% of current non-users. Of those who were drinking
      alcohol, but not using illicit drugs or smoking cigarettes, 33% thought it likely
      that they would have a problem with either drugs or alcohol at some time in the
      future compared to 7% of non-drinkers. Seventy-four per cent of children
      currently using illicit drugs thought it likely they could have a substance abuse
      problem in the future compared with 8.9% of non-drug users. CONCLUSION: Based on
      prevalence data from this sample, these results found that non-smokers had
      unrealistic beliefs about their likelihood of taking up smoking within a year and
      that many current smokers had equally unrealistic beliefs about giving up the
      habit. Adolescents had more realistic expectations about future alcohol use. When
      it came to illicit drug use, adolescents were clear in their beliefs about future
      use: very few non-users believed they would initiate use whilst current users
      believed they would continue to use. Many young people were uncertain about
      future substance use, a position which provides opportunity for drug-education
      programmes. The hypothesis that younger children would have less realistic
      beliefs about future use than older children was not supported.

PMID- 12069434
TI  - Do the risk factors associated with conduct problems in adolescents vary
      according to gender?
AB  - The present paper examines whether there are gender differences in the
      associations between conduct problems and risk factors such as family conditions,
      peer influence, leisure activities, school-related variables and pubertal timing.
      We analysed self-reported data collected as part of a large general population
      study of Norwegian adolescents (N=9342). On the basis of earlier studies, conduct
      problems were decomposed into three dimensions, labelled theft and vandalism,
      school opposition and covert behaviour. The first dimension includes different
      kinds of theft and vandalism, whereas the second includes school-related conduct
      problems of an overt aggressive kind. The last dimension reflects avoidance of
      arenas under adult control. Whether or not gender differences were detected
      depended on the aspect of conduct problems considered. The associations between
      risk factors and "theft and vandalism" and "school opposition" were stronger for
      boys than for girls. No gender differences were detected in the associations
      between and risk factors and "covert behaviour". Even though there were gender
      differences in the strength of these associations, the same risk factors seem to
      be relevant in explaining conduct problems for both gender groups.

PMID- 12069435
TI  - Instrumental and social/relational correlates of perceived maternal and paternal
      attachment in adolescence.
AB  - This study investigated the relationship of the affective and fostering of
      autonomy components of maternal and paternal attachment with indices of
      instrumental and social/relational competence among 172 10th and 12th grade male
      (75) and female (97) students. Sons and daughters rated fathers higher than
      mothers on fostering of autonomy. Consistent with traditional gender-role
      socialization, boys rated themselves higher than girls on several indices of
      instrumental competence, and girls rated themselves higher, in comparison with
      boys, on several indices of social/relational competence. Overall, the affective
      and fostering of autonomy dimensions of maternal and paternal attachment were
      associated with a range of instrumental and social/relational competencies.
      Parental attachments were associated with adolescent competencies in ways that
      are consistent with and that challenge traditional gender-role socialization.

PMID- 12069436
TI  - Adolescents murderers: abuse and adversity in childhood.
AB  - With rising rates of juvenile violence, an improved understanding of its causes
      is much needed. The relative absence of controlled studies based on British
      populations of murderers further increases the need for information in this area.
      This case control study examines a group of 21 imprisoned males, convicted of
      murder whilst aged 18 years or less, and compares them on a range of psychosocial
      variables to 21 convicted non-violent burglars. The groups were matched for age
      at interview and race. Results showed that lower socio-economic status, harsh
      parenting from both mother and father, and exclusion from school were
      significantly more common for murderers. Harsh parenting from the mother than
      from the father appeared to contribute more strongly. When factors were combined
      in a general adversity index, a significant difference was found between the two
      groups. The study confirms that multiple environmental factors are associated
      with murderous behaviour in young men.

PMID- 12069437
TI  - Adolescents with mental health problems: what do they say about health services?
AB  - This study explored the health-related views and experiences of adolescent users
      of mental health services through semi-structured interviews with 32 14-20-year
      olds who had been diagnosed with a mental illness. The majority of respondents
      had both negative and positive things to say about their contact with health
      services. These relate to: the doctor-patient relationship, treatment received,
      the health-care system, and the environs of the hospital or clinic. The views and
      experiences of young people with regard to their health care must be taken into
      account in efforts to boost help-seeking, attendance and compliance rates and,
      generally, to improve child and adolescent mental health services. In particular,
      further attention needs to be given to the development of empathic communication
      skills by health professionals working with adolescents with mental health
      problems. Work on the health-related views and experiences of representative
      samples of young people with mental health problems should be prioritized.

PMID- 12069438
TI  - Young people's romantic attachment styles and their associations with well-being.
AB  - This research, based on attachment theory, examined the relationships between
      romantic attachment styles, romantic attitudes and well-being among 461 tertiary
      students, aged 17-21 years. Those with secure romantic attachment styles were
      less stressed, less lonely and more satisfied academically than those with clingy
      or casual/fickle styles, independent of current relationship status.

PMID- 12069439
TI  - ASSENT-3: implications for future trial design and clinical practice.

PMID- 12069440
TI  - I have an acute myocardial infarction: open my coronary artery, stent it and keep
      full flow!

PMID- 12069441
TI  - Carotid intima-media thickness: risk assessment and scanning protocol.

PMID- 12069442
TI  - Continuous multilead ST-segment monitoring should be a part of the clinical
      routine.

PMID- 12069443
TI  - 'The heart doesn't pump, the kidneys suck'.

PMID- 12069444
TI  - C-reactive protein and prognosis after percutaneous coronary intervention.

PMID- 12069445
TI  - Chromogranin A in heart failure.

PMID- 12069446
TI  - Determinants of improvement in epicardial flow and myocardial perfusion for ST
      elevation myocardial infarction; insights from TIMI 14 and InTIME-II.
AB  - BACKGROUND: When evaluating new reperfusion regimens for ST elevation MI, it is
      important to adjust for factors that influence the likelihood of achieving normal
      epicardial flow and complete ST resolution. METHODS AND RESULTS: A total of 610
      patients from TIMI 14 contributed to the angiographic analyses. The
      electrocardiographic analyses were based on 544 patients from TIMI 14 and 763
      patients from InTIME-II. For each hour from onset of symptoms to initiation of
      pharmacological reperfusion, the odds of achieving TIMI 3 flow at 90 min or
      complete ST resolution at 60-90 min decreased significantly (P=0.03). Anterior
      location of infarction was associated with a reduction in the odds of achieving
      TIMI 3 flow or complete ST resolution. The use of abciximab as part of the
      reperfusion regimen significantly increased the odds of TIMI 3 flow (P=0.01) and
      ST resolution (P<0.001). The fibrinolytic administered (alteplase, reteplase,
      lanoteplase) did not influence the odds of TIMI 3 flow or ST resolution after
      adjusting for time to treatment, infarct location, and use of abciximab.
      CONCLUSIONS: The influence of time from symptoms on epicardial flow and STRES
      reinforces the need for increased efforts to reduce treatment delays in patients
      with ST elevation MI. The significant benefits of abciximab with respect to
      facilitation of epicardial and myocardial reperfusion are evident even after
      adjusting for time to treatment and infarct location. To adjust for determinants
      of success of reperfusion regimens, phase II trials evaluating new drug
      combinations should consider using a randomization scheme that stratifies
      patients based on infarct location and time from symptoms.

PMID- 12069447
TI  - Carotid intima-media thickness at different sites: relation to incident
      myocardial infarction; The Rotterdam Study.
AB  - AIMS: We examined whether intima-media thickness of the common carotid artery,
      carotid bifurcation, internal carotid artery and the combined measure are
      predictive of future myocardial infarction and which of the measurements has the
      strongest predictive value. METHODS AND RESULTS: We used a case-cohort approach
      in the Rotterdam Study. Ultrasound images of the common carotid artery, carotid
      bifurcation and the internal carotid artery were made. We selected the first 194
      myocardial infarctions in the total population (mean follow-up 4.6 years).
      Analyses were done using Cox regression with adjustment for age and sex. The risk
      ratios (RR) for myocardial infarction associated with mean maximum common
      carotid, bifurcation, internal carotid intima-media thickness and the combined
      measurements were 3.18 (95% confidence interval, 1.83-5.54), 4.11 (2.10-8.05),
      5.31 (1.77-15.9) and 6.27 (3.27-12.0), respectively, for the highest compared to
      the lowest quartile. The RRs for myocardial infarction per standard deviation
      increase of common carotid, bifurcation, internal carotid artery and combined
      intima-media thickness were 1.44 (1.28-1.62), 1.34 (1.17-1.53), 1.12 (0.94-1.33)
      and 1.47 (1.31-1.65), respectively. The areas under the ROC curves for the three
      measurements and the combined measure were not significantly different.
      CONCLUSIONS: Increased carotid intima-media thickness is a strong predictor of
      future myocardial infarction and all measurement sites have the same ability to
      predict future myocardial infarction.

PMID- 12069448
TI  - Frequency, characteristics, and clinical significance of transient ST segment
      elevation in patients with acute coronary syndromes.
AB  - BACKGROUND: Prior investigations of transient myocardial ischaemia have focused
      on ST depression events. Therefore, the purpose of this analysis was to determine
      the frequency, characteristics, and clinical significance of transient ST segment
      elevation in patients with acute coronary syndromes. METHODS: A secondary
      analysis from two prospective studies utilizing 12-lead ST segment monitoring was
      used to compare ST elevation vs ST depression events. RESULTS: Of 868 patients,
      177 (20%) had 574 events (242, ST elevation; 332, ST depression). Patients with
      ST elevation were more likely to have single vessel coronary artery disease,
      whereas patients with ST depression were more likely to have triple vessel
      coronary artery disease. ST elevation events were of shorter duration, more often
      associated with chest pain, and had greater ST changes than ST depression events.
      There was no difference in clinical outcome between patients with ST elevation vs
      depression; however, those with ST events were more likely to have adverse
      hospital outcomes (OR, 3.67) or death (OR, 2.03) than patients without ST events.
      After controlling for clinical prognostic factors, transient ST events observed
      with continuous ST monitoring predicted hospital death independently from signs
      of ischaemia on the initial standard 12-lead ECG. CONCLUSIONS: Transient ST
      elevation is nearly as prevalent as transient ST depression in patients with
      acute coronary syndromes. Since the vast majority of ST events are brief and
      otherwise clinically silent, ST segment monitoring is more efficacious in
      detecting ischaemic events and in predicting adverse clinical outcomes than
      patients' symptoms or the initial standard 12-lead ECG.

PMID- 12069449
TI  - The prognostic importance of creatinine clearance after acute myocardial
      infarction.
AB  - AIMS: The purpose of this study was to assess renal dysfunction as an independent
      predictor of mortality after acute myocardial infarction. METHODS: The study
      population was 6252 patients with a myocardial infarction admitted alive from
      1990 to 1992. The mortality status was obtained after at least 6 years. RESULTS:
      Cox proportional-hazards model demonstrated that the unadjusted risk ratio
      associated with a calculated creatinine clearance < or =40 ml x min(-1) compared
      to a clearance above 85 ml x min(-1) was 7.1 (95% confidence interval 6.2-8.0).
      Adjustment for multiple available covariates reduced this risk to 2.0 (1.6-2.4).
      The unadjusted risk ratio associated with clearance from 41 to 55 ml x min(-1)
      and from 71 to 85 ml x min(-1) was 3.7 (3.3-4.2) and 1.5 (1.3-1.7) respectively,
      but after adjustment for all available variables these risks were reduced to 1.4
      (1.2-1.6) and 1.1 (0.9-1.3) respectively. CONCLUSION: Renal dysfunction is an
      important risk factor after acute myocardial infarction. When the risk is
      adjusted for available competing risk factors only severely reduced renal
      function is associated with an important and independent risk of mortality after
      acute myocardial infarction. The risk of a moderate reduction in renal function
      is almost fully explained by an association with other conditions.

PMID- 12069450
TI  - Acute rise of circulating vascular endothelial growth factor-A in patients with
      coronary artery disease following cardiothoracic surgery.
AB  - AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and
      vasoprotective molecule whose expression is modulated by hypoxia and inflammatory
      mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are
      influenced by pre-existing coronary artery disease and by changes in circulating
      interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured
      prior to and at various time intervals following surgery in individuals with
      angiographically normal coronary arteries requiring cardiac valve replacement (N
      group) and in patients with coronary artery disease and stable angina undergoing
      coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not
      significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group
      (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise
      of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a
      maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid
      increase of plasma IL-6 in both groups, but the rise was significantly larger in
      CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A.
      Furthermore, in patients with CAD there was a significant correlation between the
      change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings
      demonstrate that in patients with coronary artery disease cardiothoracic surgery
      leads to an acute rise in VEGF-A. We suggest that this rise may result from an
      interaction between the pre-existing atheromatous process and a systemic increase
      of inflammatory mediators.

PMID- 12069451
TI  - The prognostic value of pre-procedural plasma C-reactive protein in patients
      undergoing elective coronary angioplasty.
AB  - AIMS: The acute phase reactant C-reactive protein is an important prognostic risk
      factor in patients with both stable and unstable coronary artery disease. The
      potential prognostic implications of an abnormal pre-procedural C-reactive
      protein concentration in patients undergoing elective coronary angioplasty may be
      relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma
      levels of C-reactive protein were measured in 501 patients with stable coronary
      artery disease undergoing elective coronary angioplasty. The incidence of death
      or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients
      with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in
      patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9).
      Survival without death, myocardial infarction, urgent revascularization or
      hospital admission for unstable angina was significantly lower in patients with
      an increased C-reactive protein vs patients with a normal C-reactive protein (log
      rank 14.62, P<0.0001). Logistic regression analysis identified an increased C
      reactive protein level as a strong independent predictor of event-free survival
      (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive
      protein levels are increased in 45% of patients undergoing elective coronary
      angioplasty. An increased C-reactive protein level is a powerful independent
      prognostic indicator for subsequent cardiac events, suggesting that late clinical
      outcome is markedly influenced by pre-procedural systemic activation of
      inflammation.

PMID- 12069452
TI  - Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for
      mortality.
AB  - BACKGROUND: In chronic heart failure, several hormonal systems are activated with
      diagnostic and prognostic implications. We tested the hypotheses that serum
      Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of
      neuroendocrine cells -- is increased in chronic heart failure and that CgA levels
      are a predictive factor for mortality. METHOD AND RESULTS: In 160 patients with
      chronic heart failure, we measured serum CgA and other neuroendocrine hormones.
      The results showed that CgA is increased in chronic heart failure and the
      increase is related to the clinical severity of the syndrome: CgA levels in New
      York Heart Failure (NYHA) class II (median 146.9 ng x ml(-1), inter-quartiles
      108.3-265.5) were significantly higher (P<0.05) than in class I (median 109.7 ng
      x ml(-1), inter-quartiles 96.7-137.6), and significantly lower (P<0.05) than in
      class III (median 279.0 ng x ml(-1), inter-quartiles 203.6-516.1). Class IV
      patients showed the highest serum levels of CgA (median 545.0 ng. ml(-1), inter
      quartiles 231.8-1068.3), being statistically significantly different from class
      III patients (P<0.001). The association between survival and some recognized
      variables of prognostic significance, including CgA was also studied. The results
      showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA
      class and CgA were significant univariate prognosticators; however, in the
      multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class
      were the only independent predictive factors for mortality (P<0.005, RR=1.22, 95%
      CI=1.06-1.41 and P=0.04, RR=1.58, 95% CI=1.02-2.46, respectively). CONCLUSIONS:
      CgA is a pro-hormone, precursor of several active fragments likely to exert
      biological effects in chronic heart failure. CgA serum levels are increased in
      patients with chronic heart failure and are a predictive factor for mortality.

PMID- 12069453
TI  - Gene-specific response of dynamic ventricular repolarization to sympathetic
      stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome.
AB  - AIMS: Differences in the sensitivity of the genotype of the congenital long QT
      syndrome to sympathetic stimulation have been suggested. This study compared the
      influence of sympathetic stimulation on continuous corrected QT (QTc) intervals
      between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome. METHODS AND
      RESULTS: We recorded a 12-lead electrocardiogram continuously before and after
      bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous
      infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13
      control patients. The QT intervals and previous RR intervals of all beats were
      measured semi-automatically, and the QTc intervals of all beats were calculated
      by Bazett's method. The dynamic response of the RR interval to epinephrine was no
      different between the four groups. The QTc was prolonged remarkably (477+/-42 to
      631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally
      decreased (at peak of epinephrine), and remained prolonged at steady state
      conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1
      patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39
      ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened
      to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc
      was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms;
      P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1
      and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%,
      controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state. CONCLUSION: Our
      data suggest that the dynamic response of ventricular repolarization to
      sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may
      explain why the trigger of cardiac events differs between the genotypes.

PMID- 12069454
TI  - Venous thromboembolism in young women; role of thrombophilic mutations and oral
      contraceptive use.
AB  - AIMS: The interaction between the R506Q mutation of factor V and the G20210A
      mutation of prothrombin with oral contraceptives on venous thromboembolism was
      evaluated. METHODS AND RESULTS: Three hundred and one women of reproductive age
      who had venous thromboembolism (140 while using oral contraceptives) and 650
      healthy women (173 on oral contraceptives at presentation) were examined. Of the
      patients, 19.3% were carriers of R506Q (two homozygotes) and 9.6% were
      heterozygous carriers of G20210A; eight patients (2.7%) were heterozygous for
      both mutations. Among controls, 2.9% were carriers of R506Q, 3.1% of G20210A,
      while one case was a heterozygous carrier of both mutations. The relative risk
      (odds ratio) associated with carriership of R506Q or G20210A mutations was 10.3
      and 4.7, respectively; it was 45.6 in carriers of both mutations. The odds ratio
      of using oral contraceptives in the absence of both mutations was 2.4. The odds
      ratios according to oral contraceptives use and the presence of R506Q or G20210A
      or both mutations were 41.0, 58.6 and 86.5, respectively. While the odds ratio
      for R506Q remains elevated (8.9) in non-oral contraceptive users, the odds ratio
      for G20210A was 2.0 and did not reach statistical significance. CONCLUSIONS: Our
      data showed a strong interaction between oral contraceptive use and the presence
      of either R506Q or G20210A mutations. In non-oral contraceptive users the risk of
      venous thromboembolism was significantly increased in carriers of R506Q but not
      in those with the G20210A mutation.

PMID- 12069455
TI  - Impairment of coronary microvascular flow in hypertrophic cardiomyopathy.

PMID- 12069457
TI  - Unenhanced helical CT in the investigation of acute flank pain.
AB  - Unenhanced helical CT has emerged as the imaging technique of choice for the
      investigation of patients presenting with acute flank pain and suspected
      nephroureteric stone disease. There are several signs identifiable on unenhanced
      CT that support a diagnosis of stone disease. However, there are many pitfalls,
      that may confound a correct diagnosis. Some of the common pitfalls, together with
      methods to avoid such occurrences, will be discussed. A review of some of the
      common alternative diagnoses that may mimic the symptoms of nephroureteric stone
      disease is illustrated.

PMID- 12069458
TI  - Variants of sternal insertion of the pectoral muscle on mammography: a pictorial
      review.
AB  - The aim of this pictorial review is to demonstrate the diverse presentations of
      the medial insertion of pectoralis major on mammography. A collection of cases
      demonstrating the variations in appearance of this muscle insertion are
      presented. The factors contributing to the appearances of this artifact, the
      differential diagnoses and useful further investigations are discussed.
      Familiarity with the different presentations of this muscle insertion will
      facilitate recognition and prevent unnecessary investigations.

PMID- 12069459
TI  - Magnetic resonance imaging of cerebral venous sinus thrombosis.
AB  - Cerebral venous sinus thrombosis (CVST) represents a diagnostic challenge due to
      the diversity of clinical presentation. The radiologist should be aware of the
      common neurological features. Unenhanced CT may show the first indications of
      venous sinus occlusion. Confirmatory diagnostic imaging should be performed with
      magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or
      computed tomography (CT) venography. We illustrate the MRI and MRV features of
      the thrombosed venous sinus and venous oedema or infarction and discuss the
      diagnostic limitations of these techniques.

PMID- 12069460
TI  - Does addition of CT pelvic venography to CT pulmonary angiography protocols
      contribute to the diagnosis of thromboembolic disease?
AB  - AIM: To evaluate the contribution which addition of pelvic computed tomography
      venography (CTV) to a standard CT pulmonary angiography (CTPA) imaging protocol
      makes to a definitive diagnosis of thromboembolic disease. MATERIALS AND METHODS:
      One hundred and six consecutive patients over the age of 55 years referred for
      (CTPA) for suspected pulmonary embolism between June and November 1999 had pelvic
      CTV performed at the time of the CTPA study. RESULTS: Ninety-six of 106 CTPA
      studies were technically adequate. In total, 29/96 (29.6%) CTPA studies were
      positive for pulmonary embolism, 10/96 (10.4%) CTV studies were positive and five
      of these 10 examinations showed venous thrombus when the CTPA study was negative
      (n = 4) or equivocal (n = 1). CONCLUSION: Addition of CTV shows residual thrombus
      in the pelvis in a proportion of patients with positive CTPA studies and
      demonstrates venous thrombus in a small number of patients with no CT evidence of
      pulmonary embolism.

PMID- 12069461
TI  - The early magnetic resonance imaging features of the knee in juvenile idiopathic
      arthritis.
AB  - AIMS: Early diagnosis of juvenile idiopathic arthritis (JIA) facilitates earlier
      more aggressive therapy, and improved outcome. Recognition of the features of
      early, untreated JIA on magnetic resonance imaging (MRI) will improve disease
      detection and expedite treatment. This study aims to highlight the relevant MRI
      features. METHODS: MRI examinations of the knee joint were performed on 11
      children with clinically confirmed, early, untreated JIA. The MRI images were
      obtained at a mean of 2 months after symptom onset and independently evaluated by
      two consultant paediatric radiologists. RESULTS: Abnormalities were found on all
      MRI examinations. Synovial hypertrophy, joint effusions, popliteal lymph nodes
      and soft tissue swelling were present in all patients. Gadolinium DTPA
      enhancement improved the detection of synovial hyperplasia. Metaphyseal splaying
      and condylar overgrowth were seen in five cases (41%), oedema of the lateral
      collateral ligament in two cases (18%) and superficial cartilage thinning in one
      case. Bony erosions and deep cartilage destruction were not demonstrated.
      CONCLUSION: MRI of the knee joint identifies early joint changes which are
      distinct from those in later disease. The presence of these features should alert
      the radiologist to the possible diagnosis of JIA and post gadolinium DTPA
      sequences should be performed. Gadolinium DPTA enhancement increases the
      sensitivity for the detection of inflammatory changes in JIA.

PMID- 12069462
TI  - Age as a predictive factor of mammographic breast density in Jamaican women.
AB  - AIM: We sought to determine the relationship between age, and other clinical
      characteristics such as parity, oestrogen use, dietary factors and menstrual
      history on breast density in Jamaican women. METHODS AND MATERIALS: A
      retrospective study was done of 891 patients who attended the breast imaging
      unit. The clinical characteristics were extracted from the patient records.
      Mammograms were assessed independently by two radiologists who were blinded to
      the patient clinical characteristics. Breast densities were assigned using the
      American College of Radiology (ACR) classification. RESULTS: The concordance
      between the ACR classification of breast density between the two independent
      radiologists was 92% with k = 0.76 (SE = 0.02, P < 0.001). Women with low breast
      density were heavier (81.3 +/- 15.5 kg vs 68.4 +/- 14.3 kg, P < 0.0001, mean +/-
      standard deviation (SD)) and more obese (body mass index (BMI), 30.3 +/- 5.8 kg
      m(-2) vs 26.0 +/- 5.2 kg m(-2), P < 0.0001). Mammographic breast density
      decreased with age. The age adjusted odds ratios (ORs) for predictors
      significantly related to high breast density were parity, OR = 0.79
      (95%CIratio0.71, 0.88), weight, OR = 0.92 (95% CIratio0.91, 0.95), BMI, OR = 0.83
      (95% CIratio0.78, 0.89), menopause, OR = 0.51 (95% CIratio0.36, 0.74) and a
      history of previous breast surgery, OR 1.6 (95% CIratio1.1, 2.3). CONCLUSION: The
      rate decline of breast density with age in our population was influenced by
      parity and body composition.

PMID- 12069463
TI  - What do patients know about ultrasound, CT and MRI?
AB  - OBJECTIVES: To establish the level of patient knowledge of ultrasound (US),
      computed tomography (CT) and magnetic resonance imaging (MRI); to describe
      patient information-seeking behaviour before attendance; and to assess patients'
      understanding of the main aspects of scanning examinations. DESIGN: Survey of
      people attending for ultrasound, CT and MRI using a questionnaire, including 12
      statements on simple aspects of procedures, to be indicated as true or false.
      SETTING: Radiology department of an acute teaching hospital NHS Trust in the
      north-east of Scotland. PARTICIPANTS: A convenience sample of 500 out-patient,
      non-emergency first time attenders for ultrasound (300), computed tomography
      (150), and magnetic resonance imaging (50). RESULTS: An 82% response rate to the
      questionnaire was achieved. Less than half the patients (48.9%, 182/372)
      indicated they knew the type of investigation they had been referred for. When
      responses were compared with referral letters, 64% (238/372) were incongruent.
      Few participants hadsought information (32%, 120/372), but of those who had the
      main source was family and friends (72%, 86/120). Seven participants searched the
      Internet. Eighty-two percent (308/372) of participants reported having been given
      an explanation of why an investigation was necessary. The majority of
      participants (67.8%, 251/372) expected to receive their results within 2 weeks.
      The mean score on the 12 true/false knowledge statements was 3.8, and 17%
      (65/372) answered 'Don't know' to all the statements. One person answered all
      questions correctly. CONCLUSIONS: Patients were not well informed regarding these
      investigations. This has significant implications for information-giving
      strategies and informed consent.

PMID- 12069464
TI  - The sonographic appearance of acute focal pyelonephritis 8 years experience.
AB  - AIM: Acute focal pyelonephritis (AFP) is a variant of pyelonephritis in which
      single or multiple discrete areas show changes of inflammation. The reported
      sonographic appearances of AFP are varied but are typically described as being
      echopoor. The purpose of this study was to review the sonographic appearances of
      AFP and attempt to explain the range of findings by correlation with clinical
      details. MATERIALS AND METHODS: We reviewed retrospectively the sonographic
      findings and medical records of 17 cases of AFP. The study group consisted of 13
      women and four men (mean age 20 years). Lesions were designated as echogenic,
      echopoor or of mixed echogenicity as compared to the adjacent renal cortex, and
      to the liver or spleen. RESULTS: The abnormal areas were echogenic in 12
      patients, echopoor in three and of mixed echogenicity in two. An attempt was made
      to explain the variation in appearances by correlation with clinical details
      including the patient's age, the duration of symptoms, the length of antibiotic
      treatment and the presence of haematuria. CONCLUSION: Areas of acute focal
      pyelonephritis may be echogenic, echopoor or of mixed echogenicity. Our data
      would suggest that areas of increased echogenicity are more common. There is no
      discernible correlation with clinical findings.

PMID- 12069466
TI  - Transcranial Doppler sonography in children: review of a seven-year experience.
AB  - AIM: We report the use of transcranial Doppler sonography (TCD) examinations in
      children (mean age 12.7 years; range 0.5-18 years) without an open fontanelle,
      using TCD equipment with a 2 MHz pulse wave transducer. Our results over a 7-year
      period are described. MATERIAL AND METHODS: A total of 858 children were referred
      from the paediatric outpatient department. All patients were divided into three
      groups according to the reason for referral. RESULTS: We found positive
      pathological results in the following: (1) headache and orthostatic dysregulation
      (0.4%, three out of 728); (2) acute neurological symptoms (5.4%, six out of 112);
      (3) other indications (22.2%, four out of 18). The positive predictive value of
      finding an abnormality was very low (0.50). CONCLUSION: TCD examination is
      ineffective in children with non-specific headache or orthostatic dysregulation
      due to the specific limitations of this method. We found a higher percentage of
      abnormal results in children referred for other indications. However, since these
      children usually undergo MR imaging (and MR angiography, if necessary), in our
      opinion the TCD examination does not add any additional information. The value of
      TCD in children is not in the primary diagnosis of disease but in the follow up
      of known vascular processes (e.g. stenoses) or in chronic diseases including
      angiitis and sickle cell disease.

PMID- 12069465
TI  - Is carbon dioxide as an insufflation agent for double contrast barium enema still
      worthwhile after a same-day flexible sigmoidoscopy?
AB  - PURPOSE: The aim of the study was to evaluate the efficacy of a double-contrast
      barium enema (DCBE) with CO(2) as a distending gas after a screening flexible
      sigmoidoscopy for reducing abdominal distension after an examination. PATIENTS
      AND METHODS: A total of 165 DCBEs for patients with positive faecal occult blood
      tests were randomly allocated to a CO(2) group (n = 83) and a control group (n =
      82) using air. Abdominal radiograph were taken before the DCBE, immediately
      following it, and 30 minutes later to determine residual bowel gas. The degree of
      abdominal discomfort was recorded using a scoring system. RESULTS: The patients
      in the CO(2) group had significantly smaller amounts of residual gas 30 minutes
      after the DCBE than did the control group, both in the colon (P < 0.02) and in
      the small intestine (P < 0.001). There was significantly less abdominal
      distension after the DCBE in the CO(2) group compared to the control group (P <
      0.001). The abdominal discomfort score at 30 minutes after CO(2) correlated with
      the residual gas in the small intestine (r = 0.390,P = 0.003) but not in the
      colon (r = 0.155, P = 0.15). The quality of the images and the number of polyps
      detected did not differ between two groups. CONCLUSIONS: We concluded that using
      CO(2) when administering a DCBE after a screening sigmoidoscopy was useful for
      relieving abdominal discomfort following the examination; furthermore, it did not
      impair the diagnostic ability of the DCBE.

PMID- 12069467
TI  - Interpreting regional myocardial magnetic resonance imaging data: a new method
      for collation with angiographic findings in patients with coronary artery
      disease.
AB  - The magnetic resonance imaging (MRI) assessment of myocardial function and
      perfusion is a valuable complementary technique to coronary angiography. We
      describe a method of presenting and collating regional MRI data with the
      angiographic findings as annotated by the Green Lane reporting system. Routine
      clinical use of this approach is likely to increase the accuracy of MRI data
      interpretation and to influence both medical and interventional treatment
      strategies.

PMID- 12069468
TI  - The use of melatonin as an alternative to sedation in uncooperative children
      undergoing an MRI examination.
AB  - AIM: Children who are uncooperative, due either to their age or medical
      condition, usually require sedation or a general anaesthetic (GA) to ensure
      immobility during magnetic resonance imaging (MRI) examination. These procedures
      have a risk of respiratory compromise and loss of vital reflexes. Melatonin
      induces a natural sleep with no known complication or risk of respiratory
      compromise. We aimed to evaluate the use of melatonin in these uncooperative
      children. MATERIAL AND METHODS: An unselected group of 40 children, who had been
      referred for an MRI examination of the brain under sedation or GA, were chosen to
      receive melatonin instead. They all received 10 mg of melatonin and 17 children
      additionally underwent some form of sleep deprivation. The number of children who
      went to sleep and had a successful MRI examination was recorded. RESULTS: Twenty
      six children (65%) went to sleep and of these 22 (55%) had a successful MRI
      examination. In the 17 children who underwent sleep deprivation, 13 (76%) went to
      sleep and had a successful MRI examination. There was no complication.
      CONCLUSIONS: Melatonin may provide an alternative to conventional sedation
      regimes and GA for uncooperative children undergoing an MRI examination. The use
      of sleep deprivation improves the success rate and there is no risk of
      respiratory compromise.

PMID- 12069469
TI  - Effect of contrast-enhanced computed tomography on diagnosis and management of
      acute abdomen in adults.
AB  - AIM: To determine the impact of computed tomography (CT) on the diagnosis and
      treatment plan in patients with acute abdominal pain. MATERIALS AND METHODS: A
      prospective study was undertaken in 125 adult patients presenting with acute
      abdominal pain (74 men and 51 women; 40.2 +/- 19.3 years; range, 18-92). Changes
      in diagnosis, gain in percentage diagnostic certainty and changes of treatment
      plan of the surgeons in the emergency department before and after CT were
      evaluated. Pre- and post-CT diagnoses were compared with the final diagnoses.
      RESULTS: CT findings changed the initial diagnosis in 40 (32.0%) patients. The
      diagnostic certainty was 58.3 +/- 22.9% before CT, and its gain after CT was 21.9
      +/- 18.5 points (P < 0.0001). Post-CT diagnoses were consistent with the final
      diagnosis in 116 patients (92.8%), while pre-CT diagnoses were correct in 89
      patients (71.2%; P < 0.0001). Initial treatment plans were changed in 31 (24.8%)
      patients after CT. In 57 (45.6%) patients, CT information changed diagnoses
      and/or treatment plans. No significant differences were observed in the
      diagnosis, diagnostic certainty and treatment plan among four surgeons.
      CONCLUSION: Contrast-enhanced CT frequently changed the clinical diagnoses with
      increased diagnostic certainty and the initial treatment plans.

PMID- 12069470
TI  - Recurrent or residual pelvic bowel cancer: accuracy of MRI local extent before
      salvage surgery.
AB  - PURPOSE: To determine pre-operative MRI accuracy in assessing local disease
      extent in recurrent/residual pelvic bowel cancer by comparing MRI assessment and
      staging examination under anaesthesia (EUA), with laparotomy/histopathological
      findings. MATERIALS AND METHODS: Twenty-seven consecutive patients with recurrent
      (n = 21) or residual (n = 6) pelvic bowel cancer (13 of the rectum, eleven of the
      anus and three of the colon) underwent EUA and pelvic MRI (1T) using a phased
      array pelvic coil. Retrospective analysis of eight specific anatomical regions
      for tumour involvement on MRI was performed. Findings at EUA and biopsy were
      recorded. The MRI and EUA findings were correlated with findings at surgery and
      histopathology. Statistical comparison between MRI and EUA results was performed
      using the chi-squared test. RESULTS: Overall MRI accuracy in determining tumour
      invasion for all sites assessed was 452/499 (91%), sensitivity was 95/109 (87%),
      specificity was 357/390 (92%), positive predictive value (PPV) was 95/128 (74%)
      and negative predictive value (NPV) was 357/371 (96%). PPV and NPV for specific
      areas were 21/38 (55%) and 134/136 (99%) for genitourinary tract, 4/6 (67%) and
      61/65 (94%) for pelvic side wall, 21/26 (81%) and 40/41 (98%) for pelvic floor,
      1/6 (17%) and 40/43 (93%) for the posterior pelvis pre-sacrum/sacrum. For those
      anatomical sites evaluated by both EUA and MRI, MRI was superior to EUA, with an
      accuracy of 89% vs 73% (P < 0.05). CONCLUSION: MRI is an accurate technique for
      assessing disease extent in recurrent/residual pelvic bowel cancer.

PMID- 12069471
TI  - Submucosal rectal lipoma presenting as rectal prolapse.

PMID- 12069472
TI  - Radiological findings and molecular genetic confirmation of cleidocranial
      dysplasia.

PMID- 12069473
TI  - Agenesis of the right lung presenting as a pulmonary infection.

PMID- 12069474
TI  - Acute liquefaction of lipoma of the breast.

PMID- 12069475
TI  - Synchronous serous cystadenomas of the pancreas.

PMID- 12069476
TI  - Adrenal pheochromocytoma and controlateral myelolipoma.

PMID- 12069477
TI  - Use of Doppler ultrasound of the SMA for Crohn's disease activity evaluation in
      clinical practice.

PMID- 12069478
TI  - Consultant assessment and appraisal.

PMID- 12069480
TI  - Dementia: Biological and Clinical Advances. The Rotman Research Institute
      abstracts, 2001.

PMID- 12069483
TI  - A lifetime perspective on foraging and mortality.
AB  - Food intake carries many potential risks which may impair an animal's
      reproductive success not only in the current breeding cycle, but also for the
      rest of its lifetime. We examine the lifetime trade-off between the costs and
      benefits of food intake by presenting a simple animal foraging model, where each
      unit of food eaten carries with it a risk of mortality. We show that the optimal
      food intake rate over an animal's lifetime, for both semelparous and iteroparous
      animals, is not maximal. Instead, animals are required to strike a balance
      between the immediate reproductive benefits of gathering food and the future
      reproductive costs incurred by the food's mortality risk. This balance depends
      upon the lifespan of the animal as well as the nature of the risk. Different
      mortality risks are compared and it is shown that a mortality risk per unit time
      spent foraging is not, in general, equivalent to a mortality risk per unit of
      food consumed. The results suggest that a mortality risk per unit of food
      consumed, such as that presented by the presence of a toxin or of a parasite in
      the diet, has important consequences for feeding behaviour and is a possible
      factor involved in food intake regulation.

PMID- 12069484
TI  - Hydrogen bonds and the catalytic mechanism of human carbonic anhydrase II.
AB  - A new model for catalysis of human carbonic anhydrase II is suggested. The model
      is based on the X-ray structure of the hydrogen bond network in the catalytic
      site. The outer part of the network is proposed to adjust the p K(a) of the
      catalytic site to the experimentally observed value of about 7. The inner part of
      the network is proposed to become a low-barrier hydrogen bond network in the
      transition state. The energy released in forming the low-barrier hydrogen bond
      network is used to catalyse the interconversion of CO(2) and HCO(3)(-). The
      suggested molecular mechanism is consistent with the generally accepted kinetic
      scheme for human carbonic anhydrase II.

PMID- 12069485
TI  - On the probability model for asthma attacks.
AB  - In environmental epidemiology, the impact of environmental agents on symptoms or
      health status is of interest. This influence is described quantitatively in the
      theory of Whittemore & Keller (1979). They formulated a logistic model for
      individuals that is useful in evaluation of panel studies in which each
      participant protocols whether he does or does not have a certain symptom each
      day. In the present paper an equation for the prevalence of symptoms in the study
      population that is defined as the fraction of symptomatic subjects is deduced
      from the model for individuals. The model for the aggregated quantity depends on
      the individuals' parameters in a nonlinear manner. The relationship between the
      individual-based model and the corresponding population-based model is
      illustrated by means of a simulated panel. Bayesian estimates of the parameters
      are calculated and compared for both approaches. Bayesian inference enables to
      apply the prevalence model to a population of non-identical individuals. For such
      a heterogeneous population, we observe an attenuation of environmental effects on
      the aggregated symptom prevalence in comparison to the individual-based approach.
      The presented theory is applicable not only to panel studies but also in time
      series analysis of prevalences and incidences.

PMID- 12069486
TI  - A cellular automata model of ligand passage over a protein hydrodynamic
      landscape.
AB  - The subject of ligand passage to an active site on a protein is addressed.
      Current views on the mechanism and the possible role of surface water are
      discussed. A theory is presented in which the pattern of hydropathic states of
      protein surface amino acid side chains is invoked as the influence on the
      relative hydrophobic effects of nearby water. The theory describes a ligand
      passage through the hydrodynamic near-surface water which exhibits temporary
      organized cavities resembling the chreodes introduced by Waddington. The passage
      of the ligand to the active site is facilitated by this dynamic mechanism.
      Cellular automata models of preferential directional diffusion through these
      chreodes support the theory. The theory may be invoked to explain a number of
      ligand-active site observations and serves as an idea for further studies.

PMID- 12069487
TI  - The role of colony organization on pathogen transmission in social insects.
AB  - Social organisms are especially vulnerable to pathogens due to the homogeneity of
      the colony, and the close proximity and extensive interactions among its members.
      However, the social organization of these groups also offers the potential to
      provide an effective barrier against the transmission of pathogens within the
      colony. Social insects with their elaborate colony organizations provide an ideal
      model system to develop and test this hypothesis. While the different elements of
      colony organization are generally assumed to be products of ergonomic selection,
      in this paper we address how the same elements could influence the transmission
      of pathogens. By developing a simple model, we explore how three parameters of
      colony organization, division of labor, interaction network and colony demography
      could influence the transmission of pathogens. We find that heterogeneity among
      individuals in terms of division of labor alone has little effect on the spread
      of an infection in the colony and the scenario is indistinguishable from one in
      which all the individuals are homogeneous. However, division of labor, combined
      with heterogeneity in the interaction network and demographic schedules reduce
      the spread of an infection.

PMID- 12069488
TI  - Species positions and extinction dynamics in simple food webs.
AB  - Recent investigations on the structure of complex networks have provided
      interesting results for ecologists. Being inspired by these studies, we analyse a
      well-defined set of small model food webs. The extinction probability caused by
      internal Lotka-Volterra dynamics is compared to the position of species.
      Simulations have revealed that some global properties of these food webs (e.g.
      the homogeneity of connectedness) and the positions of species therein (e.g.
      interaction pattern) make them prone to modelled biotic extinction caused by
      population dynamical effects. We found that: (a) homogeneity in the connectedness
      structure increases the probability of extinction events; (b) in addition to the
      number of interactions, their orientations also influence the future of species
      in a web. Since species in characteristic network positions are prone to
      extinction, results could also be interpreted as describing the properties of
      preferred states of food webs during community assembly. Our results may
      contribute to understanding the intimate relationship between pattern and process
      in ecology.

PMID- 12069489
TI  - The regulatory basis of melanogenic switching.
AB  - Melanin produced in follicular melanocytes is the major basis for pigmentation of
      hair and wool in mammals. Two major types of melanin may be synthesized, the
      black/brown eumelanin and the reddish/yellow pheomelanin. Based on available cell
      biological evidence and reasonable assumptions, a mathematical model is developed
      to improve our understanding of melanogenic switching, i.e. the switching between
      eumelanin and pheomelanin production depending on the extracellular signalling
      context. In 1993, Ito proposed that melanogenic switching is due to the covalent
      binding of the intermediate DOPAquinone to the enzyme glutathione reductase. We
      were only able to obtain a good fit to available experimental data on the
      relation between pheomelanin levels and the activity of the key enzyme tyrosinase
      by taking Ito's hypothesis into account. Thus, our results support Ito's
      hypothesis, and suggest that melanogenic switching may be due to a jump between
      two stable production pattern states when the tyrosinase activity varies between
      two bifurcation levels. This implies that small changes in the levels of external
      regulatory factors may cause an accentuated change in the proportion of the
      produced colour pigments and may explain the fact that mammalian coat patterns
      often exhibit sharply delimited patches of either black or reddish colour.

PMID- 12069490
TI  - Biomass-diversity responses and spatial dependencies in disturbed tallgrass
      prairies.
AB  - Monotonic, hump-shaped and zero-correlation productivity-diversity relationships
      have been found to date in many ecosystems. This diversity of responses has
      puzzled ecologists in their search for general principles on ecosystem
      functioning. Some state that the scale of observation is crucial in defining this
      relationship. We have developed a spatial model of tallgrass prairies where
      biomass and litter dynamics are defined by uncoupled difference equations. In
      this system, we periodically apply prescribed fire as a disturbance that
      propagates through neighboring cells. The model shows percolation thresholds at
      points where small-scale spatial heterogeneity and large-scale, global
      correlation coexist, resulting in power-law distributions in available areas for
      non-dominant species. These points maximize the biomass-diversity relationship.
      Our results suggest that spatial dependencies and the disturbance heterogeneity
      hypothesis are the cornerstone processes accounting for unimodality in
      productivity-diversity relationships.

PMID- 12069492
TI  - Thermodynamics of systems of biochemical reactions.
AB  - When a reaction system described in terms of species is in a certain state, the
      Gibbs energy G provides the means for determining whether each reaction will go
      to the right or the left, and the equilibrium composition of the whole system can
      be calculated using G. When the pH is specified, a system of biochemical
      reactions is described in terms of reactants, like ATP (a sum of species), and
      the transformed Gibbs energy G' provides the means for determining whether each
      reaction will go to the right or the left. The equilibrium composition of the
      whole system can be calculated using G'. Since metabolism is complicated, the
      thermodynamics of systems of reactions like glycolysis and the citric acid cycle
      can also be considered at specified concentrations of coenzymes like ATP, ADP,
      NAD(ox), and NAD(red). This is of interest because coenzymes tend to be in steady
      states because they are involved in many reactions. When the concentrations of
      coenzymes are constant, the further transformed Gibbs energy G" provides the
      means for calculating whether each reaction will go to the right or the left, and
      the equilibrium composition of the whole system can be calculated using G". Under
      these conditions, a metabolic reaction system can be reconceptualized in terms of
      sums of reactants; for example, glycolysis can be represented by C(6)=2C(3),
      where C(6) is the sum of the reactants with six carbon atoms and C(3) is the sum
      of the reactants with three carbon atoms. These calculations can also be
      described by use of semigrand partition functions. Semigrand partition functions
      have the advantage of containing all the thermodynamic information on a series of
      reactions at specified pH or at specified pH and specified concentrations of
      coenzymes.

PMID- 12069491
TI  - Task partitioning in a ponerine ant.
AB  - This paper reports a study of the task partitioning observed in the ponerine ant
      Ectatomma ruidum, where prey-foraging behaviour can be subdivided into two
      categories: stinging and transporting. Stingers kill live prey and transporters
      carry prey corpses back to the nest. Stinging and transporting behaviours are
      released by certain stimuli through response thresholds; the respective stimuli
      for stinging and transporting appear to be the number of live prey and the number
      of prey corpses. A response threshold model, the parameters of which are all
      measured empirically, reproduces a set of non-trivial colony-level dynamical
      patterns observed in the experiments. This combination of modelling and empirical
      work connects explicitly the level of individual behaviour with colony-level
      patterns of work organization.

PMID- 12069494
TI  - Burn-induced thymic apoptosis corresponds with altered TGF-beta(1) and Smad 2/3.
AB  - Immune suppression is a common complication of injury. Transforming growth factor
      beta(1) (TGF-beta(1)), a cytokine with diverse anti-inflammatory and anti
      apoptotic effects, may play an important role. Smad 2 and Smad 3 are
      transcription factors that mediate the effects of TGF-beta(1). We hypothesized
      that burn-induced immunosuppression would be accompanied by increased apoptosis
      in lymphoid organs, a change likely associated with changes in TGF-beta(1) and
      Smad 2/3 expression. Mice were subjected to 18% body surface area flame burn.
      Lymph nodes, spleen, and thymus were harvested at multiple time points after
      injury. TGF-beta(1) and Smad 2/3 expression and levels of apoptosis were
      determined in whole tissue and in sorted T-cells by flow cytometry, RT-PCR,
      ELISA, and Western blot. TGF-beta(1) protein expression in the thymus increased
      from 1 to 7 days. Smad 2/3 protein expression was decreased at the same time
      points. This down-regulation was more dramatic in the non-T-cells than in the T
      cells themselves. RT-PCR confirmed down-regulation of Smad 3 mRNA in the thymus
      from 3 to 6 h. Apoptosis in the thymus doubled at 1 day (6.4% control vs 12.8%
      burned), which corresponded with a marked decrease in thymus mass on subjective
      assessment. No changes were observed in other lymphoid organs. Burn injury in
      mice increases TGF-beta(1) expression in the thymus, while suppressing expression
      of its intracellular mediator, Smad 2/3. This response is most pronounced in the
      non-T-cell tissue, which suggests the thymic epithelial cells may be responsible
      for the increased thymic apoptosis. This TGF-beta(1) and Smad 2/3
      counterregulation in response to injury may represent a potential mechanism for
      postinjury immune suppression.

PMID- 12069495
TI  - Myocellular creatine and creatine transporter serine phosphorylation after
      starvation.
AB  - BACKGROUND: Myocellular creatine, which is critically important for normal energy
      metabolism, increases in rat gastrocnemius muscle after starvation via unknown
      mechanisms. Creatine (Cr) uptake across plasma membranes is governed by a single,
      specific transporter (CrTr) that shares 50% amino acid sequence identity with
      GABA/choline/betaine transporters whose functions are modulated by
      phosphorylation. METHODS: Gastrocnemius muscle was collected from adult male
      Sprague-Dawley (225-250 g) rats that were randomized to receive normal rat chow
      and distilled water ad libitum (CTL) or distilled water alone for 4 days (STV).
      Total Cr, phosphocreatine (PCr), free Cr, and ATP were measured luminometrically.
      CrTr protein expression and protein serine and tyrosine phosphorylation and mRNA
      expression were determined using immunoprecipitation and quantitative Western
      blotting and reverse transcription polymerase chain reaction (RT-PCR) analyses,
      respectively. Guanidinoacetate methyltransferase (GAMT) activity, guanidinoacetic
      acid (GAA) content, creatine kinase (CK) activity, and creatinine (Crn) content
      were assayed luminometrically or spectrophotometrically. Creatine transporter
      uptake activity was also measured in skeletal muscle membrane vesicles. Data were
      analyzed by t test. RESULTS: Total Cr and free Cr increased 26 and 280% in STV
      (32.3 +/- 1.0 and 12.9 +/- 1.4 vs 25.7 +/- 1.1 and 3.4 +/- 0.9 micromol/g wet wt,
      mean +/- SEM, respectively, P < 0.01) whereas PCr content decreased 18% (18.6 +/-
      0.8 vs 22.8 +/- 0.9 micromol/g wet wt, STV vs CTL P < 0.05). CrTr protein and
      mRNA expression, ATP, GAA, CK, GAMT, and protein tyrosine phosphorylation of CrTr
      were not significantly different between the two groups. However, protein serine
      phosphorylation of CrTr was significantly reduced by 30% (P < 0.05) and creatine
      uptake activity was significantly increased (P < 0.05) in starved animals.
      CONCLUSION: Increases in myocellular creatine content after starvation are
      associated with reduced serine phosphorylation of the creatine transporter.

PMID- 12069496
TI  - Enhanced dendritic cell antigen presentation in RNA-based immunotherapy.
AB  - BACKGROUND: Dendritic cells pulsed with mRNA provide a unique approach to tumor
      immunotherapy. We hypothesized that increased mRNA transfection efficiency and
      dendritic cell maturation would improve antigen processing and presentation as
      well as T-cell costimulation, resulting in enhanced induction of antimelanoma
      immune responses. METHODS: Immature monocyte-derived dendritic cells were
      transfected with mRNA by passive pulsing, lipofection, or electroporation.
      Dendritic cells were either left untreated or matured using the double-stranded
      RNA poly(I:C). T-Cell cultures were generated by stimulation of naive T-cells
      with each set of dendritic cells. Specific antigen presentation and specific
      effector T-cell generation were analyzed by an IFN-gamma release Elispot assay.
      RESULTS: Greatest intracellular green fluorescent protein was observed by flow
      cytometry following dendritic cell electroporation with green fluorescent protein
      mRNA. DC presentation of Mart-1/Melan A peptide, as measured by Elispot assay
      using a specific T-cell clone, was greatest following transfection with Mart
      1/Melan A mRNA by electroporation. Maturation of dendritic cells further improved
      antigen presentation regardless of transfection technique. Specific Mart-1/Melan
      A effector T cells were produced after culture of naive T cells with dendritic
      cells that were electroporated with Mart-1/Melan A mRNA and then matured, but not
      for dendritic cells that remained immature. CONCLUSIONS: Efficient mRNA
      transfection by electroporation as well as dendritic cell maturation results in
      increased levels of Mart-1/Melan A antigen presentation and enhanced production
      of antigen-specific effector T cells. This combination of strategies may be used
      to enhance immune responses to RNA-based dendritic cell vaccines.

PMID- 12069498
TI  - Competency-based student self-assessment on a surgery rotation.
AB  - BACKGROUND: Although self-assessment is an essential component of self-directed
      adult learning, few data exist regarding the ability of medical students to
      perform this important task. Therefore, the purpose of this study was to evaluate
      the ability of medical students to perform self-assessment during a third-year
      surgery clerkship. METHODS: Sixty-eight (34 male, 34 female) third-year medical
      students assessed their progress at the midpoint of an 8-week surgery clerkship
      using an 11-item, competency-based evaluation. Students compared perceptions of
      their performance with a faculty member's assessment using the identical
      evaluation form. RESULTS: Male students tended to overestimate their midclerkship
      performance compared with faculty formative and summative evaluations (3.31 +/-
      0.03 vs 3.23 +/- 0.03 and 3.28 +/- 0.03) although this did not reach statistical
      significance. Female students significantly underestimated their midclerkship
      performance compared with faculty formative and summative evaluations (3.06 +/-
      0.03 vs 3.40 +/- 0.03 and 3.45 +/- 0.03, P < 0.05 vs faculty evaluations).
      Preclerkship academic performance (first- and second-year grade point averages
      and NBME Part 1 scores) was not predictive of student self-assessment. Finally,
      women statistically outperformed men on the surgery clerkship (86.6% +/- 0.75 vs
      83.2% +/- 1.20, P < 0.05 vs male students). CONCLUSIONS: Female students tend to
      underestimate their midclerkship performance compared with male students on a
      surgery rotation. Despite lower self-assessment, female students actually
      outperform male students. Women may underreport their capabilities when compared
      with men as a result of gender differences in socialization. These gender
      differences in self-assessment may be important to recognize when faculty provide
      feedback to students.

PMID- 12069497
TI  - Selective inhibition of the epidermal growth factor receptor impairs intestinal
      adaptation after small bowel resection.
AB  - BACKGROUND: Prior indirect studies have suggested that a functional epidermal
      growth factor receptor (EGFR) appears to be indispensable for the adaptive
      response of the remnant intestine to massive small bowel resection (SBR). The
      recent availability of a specific pharmacologic EGFR inhibitor enabled us to more
      directly test the hypothesis that EGFR signaling is required for postresection
      intestinal adaptation. METHODS: Mice (C57B1/6, n = 26) underwent a 50% SBR or
      sham operation and were then given orogastric EGFR inhibitor (ZD1839, 50
      mg/kg/day) or vehicle. After 3 days, indices of adaptation (wet weight, crypt
      depth, and villus height) and apoptotic index (number of apoptotic bodies per
      crypt) were calculated in the ileum. The expression of proliferating cell nuclear
      antigen (PCNA) and activated EGFR was measured by Western blotting. RESULTS:
      ZD1839 prevented EGFR activation and the normal postresection increases in ileal
      wet weight, villus height, and crypt depth. Enterocyte proliferation was reduced
      twofold in the SBR group by ZD1839. Although not statistically significant, rates
      of enterocyte apoptosis were the highest in the inhibitor-treated mice.
      CONCLUSION: Following massive SBR, pharmacologic inhibition of the EGFR
      attenuates proliferation and the normal adaptive response of the intestine. These
      results more directly confirm the requirement of a functional EGFR as a mediator
      of the postresection adaptation response. This study demonstrates an in vivo
      application of a novel selective EGFR inhibitor and offers a unique experimental
      model to gain mechanistic insight into understanding postresection intestinal
      adaptation.

PMID- 12069499
TI  - Upregulation of arginase expression in wound-derived fibroblasts.
AB  - BACKGROUND: Wound-derived fibroblasts (WFBs) are phenotypically different from
      normal dermal fibroblasts (NFBs). We have previously shown that the wound
      phenotype correlates with expression of the inducible isoform of nitric oxide
      synthase (iNOS) in fibroblasts. l-Arginine is the sole substrate for iNOS.
      Arginase is an alternative pathway of l-arginine metabolism in wounds. To clarify
      the role of l-arginine in wound healing, we investigated arginase expression and
      activity in WFB. METHODS: Male Lewis rats underwent dorsal skin incisions and
      subcutaneous PVA sponge implantation. WFBs were harvested from sponges retrieved
      at different days postimplantation. Normal fibroblasts were obtained from
      uninjured skin by an explant technique. Arginase activity was measured by newly
      formed urea (nmol/min/mg protein) and protein expression was detected by Western
      blotting using specific antibodies for type I (AI) and type II (AII). The effect
      of transforming growth factor beta1 (TGF-beta1), interleukin-4 (IL-4),
      lipopolysaccharide, and wound fluid on arginase activity was also investigated.
      RESULTS: WFB arginase activity was significantly elevated compared with NFB
      activity at all times postwounding. This was paralleled by increased AI protein
      expression by Western blotting. AII was not detectable. TGF-beta and IL-4
      significantly increased arginase activity and protein expression whereas
      lipopolysaccharide and wound fluid did not affect it. CONCLUSIONS: The
      upregulation of the arginase expression in WFB underlines the distinct regulation
      of l-arginine metabolism in WFBs. Further work is needed to elucidate the
      functional implications.

PMID- 12069500
TI  - Vascular endothelial growth factor-mediated angiogenesis inhibition and
      postoperative wound healing in rats.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) is an angiogenic factor
      that acts by binding to specific high-affinity tyrosine kinase receptors. SU5416
      is an antiangiogenic agent that acts as a potent and selective inhibitor of the
      VEGF Flk-1/KDR receptor tyrosine kinase. SU5416 has been shown to inhibit VEGF
      dependent mitogenesis of human endothelial cells and to decrease the growth of
      xenografts of melanoma, lung carcinoma, ovarian carcinoma, and gliomas. The
      effect of pre- or perioperative use of this drug on angiogenesis and wound
      healing in the postoperative setting has not been shown. We sought to analyze the
      efficacy and safety with respect to functional dosing of SU5416 in the setting of
      wound healing. This represents an important step forward in the use of this and
      similar drugs in the perioperative setting of treatment for multiple types of
      cancers. The use of an inhibitor of VEGF receptors such as SU5416 is distinct and
      it is likely complementary to other agents in the treatment of such cancers.
      METHODS: We injected 8-week-old male Sprague-Dawley rats with SU5416 (8 or 12
      mg/kg) or dimethyl sulfoxide intraperitoneally, daily for 14 days. We then
      performed a right pulmonary lobectomy and 6-mm full-thickness punch biopsies of
      the back. Tissue perfusion measured via laser Doppler on Postoperative Day 2 was
      1.65, 1.22, and 1.14 perfusion units (P < 0.0004) for control, 8 mg/kg, and 12
      mg/kg groups, respectively. RESULTS: We successfully treated a murine model with
      functional doses of the anti-VEGF drug SU5416 so as to achieve decreased
      vascularity and blood flow in postoperative wounds. There was no effect on gross
      wound healing or infection in either control or treatment groups. Also, no drug
      related impairment of histologic healing or decrease in wound tensile strength
      was demonstrated at either 6 or 14 days. CONCLUSION: Preoperative therapy with
      functional dosing of SU5416 does not appear to have any major effect on
      postoperative morbidity or mortality in rats. We additionally conclude that
      preoperative therapy with SU5416 should be investigated further with careful
      attention to wound integrity.

PMID- 12069501
TI  - Assessing the relative contribution of individual risk factors on surgical
      outcome for gastric bypass surgery: a baseline probability analysis.
AB  - BACKGROUND: Multiple regression is the best technique for the simultaneous
      analysis of the contributions of multiple risk factors to a surgical outcome. A
      probability analysis is used to determine the relative contribution of individual
      factors to the overall outcome being assessed. We used these techniques to
      determine which of the potential risk factors had the greatest impact on adverse
      outcomes following gastric bypass surgery. METHODS: Records from 1067 consecutive
      patients undergoing Roux-Y gastric bypass at the UCLA Medical Center from
      December 1993 until June 2000 were reviewed. Major complications were used as the
      dependent variable in a multivariate logistic regression analysis, and 10 risk
      factors served as the independent variables. Based on the analysis, an average
      (i.e., baseline) patient was defined. Variations in the preoperative risk factors
      were then analyzed individually and in various combinations and their effect on
      the predicted probability for complication development was assessed. RESULTS: The
      overall major complication rate in this series was 5.8%. The average patient was
      defined as a 334-pound woman who was 42.3 years of age. For this patient, the
      predicted complication rate by probability analysis was 3.9%. The greatest
      increase in the anticipated complication rate was attributable to revisional
      procedures that increased the rate to 6.5%. Many patients have a combination of
      risk factors; to this end, a 62-year-old, male patient with a 2SD increase in
      weight (i.e., 464 pounds) who was undergoing a revision operation and had a
      history of smoking, hypertension, diabetes, and sleep apnea had a predicted
      complication rate of 33.7%. CONCLUSION: Probability analysis is a useful tool for
      determining the relative contribution of individual and combinations of risk
      factors for predicting the outcomes for surgical procedures. The four most
      influential factors for predicting a complication after gastric bypass surgery
      were; (1) male gender, (2) revisional surgery, (3) increasing age, and (4)
      increasing weight. These factors increased the predicted complication rate by 56,
      67, 28 and 28%, respectively.

PMID- 12069502
TI  - The need for a multidisciplinary approach to cancer care.
AB  - BACKGROUND: Treatment of the cancer patient is multifaceted. In addition to
      treating the cancer itself, there are additional important, "noncancer" issues to
      consider concomitantly, such as the patient's coexistent diseases, their health
      behaviors, and preventive care measures. While the need for coordination among
      surgeons, oncologists, and radiation oncologists has been well documented for
      treatment of the cancer, little attention has been paid to the importance of
      "noncancer" issues. In an attempt to characterize such issues, we performed a
      study to describe the prevalence of comorbid diseases as well as other
      "noncancer" issues (i.e., presence of poor health habits and use of preventive
      care measures) for four common, surgically related cancers. Finally, we describe
      the use of provider resources for these cancer patients. METHODS: Using a large
      population-based, nationwide patient survey, a cross-sectional analysis of lung,
      prostate, breast, and colon cancer patients who were less than 3 years from their
      diagnosis was performed. Prevalence of comorbid disease, health behaviors,
      receipt of preventive health care services, and contact with the health care
      system were characterized. Comparisons were made with a cohort of age-matched
      controls without cancer. RESULTS: Three hundred one cancer patients (29 lung, 88
      prostate, 119 breast, 65 colon) and 6745 control patients were analyzed. Among
      the cancer patients, 81% had a coexistent disease, with 59% reporting
      cardiovascular comorbidity and 17% reporting pulmonary comorbidity. The range of
      comorbidities was substantial: hypertension (24-48%), coronary disease (8-24%),
      angina (4-10%), myocardial infarction (8-31%), arrhythmia (8-19%), stroke (3-8%),
      emphysema (4-10%), asthma (5-12%), diabetes (8-18%), bronchitis (8-13%), renal
      insufficiency (3-6%), severe arthritic symptoms (34-57%). Of note, 27-39% of
      cancer patients continued to smoke tobacco (P = 0.03 vs controls), of whom 85%
      continued to smoke daily. Finally, the rates of preventive care influenza
      vaccinations in high-risk individuals for the cancer cohort was no higher than
      the rate in controls, even though the cancer patients saw a health professional
      significantly more often. Of note, the frequency of "specialists" and surgeon
      visits was significantly higher for the cancer cohort. CONCLUSION: To optimize
      cancer outcomes, successful treatment of both the cancer and the "noncancer"
      issues is required. This study demonstrates that the burden of coexistent
      diseases is considerable. We also found the prevalence of continued poor health
      behaviors (i.e., use of tobacco) as well as suboptimal performance of preventive
      care measures to be notable. Since cancer patients see specialists twice as often
      as controls, it appears paramount that specialists (surgeons included) maintain
      diligence in addressing patient comorbidities, health habits, and other
      "noncancer" measures. If the substantial rates of smoking and suboptimal
      performance of preventive care measures are an indication of the "noncancer"
      quality of care that is being provided to the typical cancer patient, then a more
      concerted effort by all providers needs to be made regarding these and other
      "noncancer" issues.

PMID- 12069504
TI  - Vitamin E and the Y4 agonist BA-129 decrease prostate cancer growth and
      production of vascular endothelial growth factor.
AB  - BACKGROUND: A biologically active form of vitamin E, alpha-tocopherol succinate
      (ATS), has been shown to induce apoptosis of hormone-refractory prostate cancer
      in vitro and inhibit cell growth in vivo. The gastrointestinal hormone peptide YY
      (PYY) has growth inhibitory activity against multiple cancer cell lines and is
      synergistic with ATS against breast and pancreatic cancer growth. BA-129, a
      specific Y4 receptor agonist, has growth inhibitory effects on pancreatic cancer
      in vitro. We investigated the effects of BA-129 and ATS on prostate cancer growth
      and evaluated their effects on vascular endothelial growth factor (VEGF)
      production. METHODS: A hormone-refractory human prostate cancer cell line, PC-3,
      was treated with ATS alone at 10 pg/ml, PYY or BA-129 alone at doses of 75 and
      500 pmol/ml, or a combination of the two agents. Cell growth was measured by MTT
      assay and hemocytometry using trypan blue. Quantitative measurement of VEGF was
      performed by ELISA. Statistical analysis was achieved by ANOVA. RESULTS: ATS
      exhibited significant (P < 0.05) growth inhibitory effects in prostate cancer
      cells. PYY also inhibited growth (P < 0.05). ATS treatment reduced VEGF
      production (P < 0.05). PYY treatment increased VEGF. When ATS was given in
      combination with BA-129, VEGF production was further reduced (P < 0.05).
      CONCLUSIONS: Both PYY and ATS inhibit growth in hormone-refractory prostate
      cancer, with augmentation when used in combination. VEGF production is inhibited
      by vitamin E, but increased by PYY. ATS abolishes the augmented VEGF response to
      PYY. Our data suggest that PYY is involved in the regulation of VEGF production
      and prostate cancer growth.

PMID- 12069503
TI  - Somatostatin receptor subtype 2 gene therapy inhibits pancreatic cancer in vitro.
AB  - BACKGROUND: Most human pancreatic adenocarcinoma cells do not express
      somatostatin receptors and somatostatin does not inhibit the growth of these
      cancers. We have demonstrated previously that somatostatin inhibits the growth of
      pancreatic cancers expressing somatostatin receptor subtype 2 (SSR2) but not
      receptor-negative cancers. SSR2 expression may be an important tumor suppressor
      pathway that is lost in human pancreatic cancer. We hypothesized that SSR2 gene
      transfer would restore the growth inhibitory response of human pancreatic cancer
      to somatostatin. METHODS: We created adenoviral constructs containing the SSR2 or
      Lac-Z gene and transfected somatostatin receptor-negative human pancreatic cancer
      cells (Panc-1). Presence of functional cell surface SSR2 protein was assessed by
      whole-cell competitive binding assays. Parental cells, Lac-Z-transfected, and
      SSR2-transfected cells were cultured in the presence and absence of somatostatin.
      The rate of cell growth was determined by direct cell counting using a
      hemacytometer (n = 8 wells/group). Cells were analyzed for expression of tumor
      suppressor proteins by Western blot. RESULTS: Panc-1 cells transfected with the
      SSR2 transgene demonstrated high-affinity specific binding of (125)I-somatostatin
      at physiologic concentrations. Expression of somatostatin receptors caused 60%
      inhibition of cell growth compared with the Lac-Z virus-treated controls (P <
      0.05 by Kruskal-Wallis/Bonferroni). There was no additional inhibition of cell
      proliferation with exogenous somatostatin. Furthermore, addition of somatostatin
      ligand antibody did not diminish the effect of SSR2 expression on cell
      proliferation. Western blot analysis revealed an upregulation of the cyclin
      dependent kinase inhibitor p27 in the SSR2-transfected cells. CONCLUSIONS:
      Expression of SSR2 by human pancreatic cancer causes significant slowing of cell
      division by a mechanism independent of somatostatin. The mechanism may involve
      upregulation of known tumor suppressor proteins. Restoration of SSR2 gene
      expression deserves further study as a potential gene therapy strategy in human
      pancreatic cancer.

PMID- 12069505
TI  - Age-dependency in hunting ability among the Ache of eastern Paraguay.
AB  - This paper examines changes in hunting ability across the lifespan for the Ache
      of eastern Paraguay. Hunting ability is decomposed into two components-finding
      prey and probability of kill upon encounter- and analyzed for important prey
      species. Results support the argument that skill acquisition is an important
      aspect of the human foraging niche with hunting outcome variables reaching peaks
      surprisingly late in life, significantly after peaks in strength. The
      implications of this study are important for modeling the role of the human
      foraging niche in the co-evolution of various outstanding human life history
      characteristics such as large brains, long lifespans, and extended juvenile
      periods.

PMID- 12069506
TI  - Paleosols and paleoenvironments of the middle Miocene, Maboko Formation, Kenya.
AB  - The middle Miocene (15 Ma) Maboko Formation of Maboko Island and Majiwa Bluffs,
      southwestern Kenya, has yielded abundant fossils of the earliest known
      cercopithecoid monkey (Victoriapithecus macinnesi), and of a kenyapithecine
      hominoid (Kenyapithecus africanus), as well as rare proconsuline (Simiolus
      leakeyorum, cf. Limnopithecus evansi) and oreopithecine apes (Mabokopithecus
      clarki, M. pickfordi), and galagids (Komba winamensis). Specific habitat
      preferences can be interpreted from large collections of primate fossils in
      different kinds of paleosols (pedotypes). Fossiliferous drab-colored paleosols
      with iron-manganese nodules (Yom pedotype) are like modern soils of seasonally
      waterlogged depressions (dambo). Their crumb structure and abundant fine root
      traces, as well as scattered large calcareous rhizoconcretions indicate former
      vegetation of seasonally wet, wooded grassland. Other fossiliferous paleosols are
      evidence of nyika bushland (Ratong), and early-successional riparian woodland
      (Dhero). No fossils were found in Mogo paleosols interpreted as saline scrub
      soils. Very shallow calcic horizons (in Yom, Ratong, and Mogo paleosols) and Na
      montmorillonite (in Mogo) are evidence of dry paleoclimate (300-500 mm MAP=mean
      annual precipitation). This is the driest paleoclimate and most open vegetation
      yet inferred as a habitat for any Kenyan Miocene apes or monkeys.
      Victoriapithecus was abundant in dambo wooded grassland (Yom) and riparian
      woodland (Dhero), a distribution like that of modern vervet monkeys.
      Kenyapithecus ranged through all these paleosols, but was the most common primate
      in nyika bushland paleosols (Ratong), comparable to baboons and macaques today.
      Mabokopithecus was virtually restricted to riparian woodland paleosols (Dhero),
      and Simiolus had a similar, but marginally wider, distribution. Habitat
      preferences of Mabokopithecus and Simiolus were like those of modern colobus
      monkeys and mangabeys. A single specimen of Komba was found in dambo wooded
      grassland paleosol (Yom), a habitat more like that of the living Senegal bushbaby
      than of rainforest galagids. A shift to non-forest habitats may explain the
      terrestrial adaptations of Victoriapithecus, basal to the cercopithecid
      radiation, and of Kenyapithecus, basal to the hominoid radiation. Both taxa are
      distinct from earlier Miocene arboreal proconsulines, oreopithecines and
      galagids.

PMID- 12069507
TI  - New Sivapithecus postcranial specimens from the Siwaliks of Pakistan.
AB  - Several new postcranial elements of Sivapithecus from the Siwaliks of Pakistan
      are described. These include a distal femur from the U-level of the Dhok Pathan
      Formation, a navicular from the Chinji Formation, and seven manual and pedal
      phalanges from the Nagri Formation. The functional morphology of these elements
      adds new detail to the reconstruction of Sivapithecus positional behavior.
      Femoral cross-sectional geometry indicates that the shaft was adapted to support
      mediolaterally directed loading. Femoral condylar asymmetry and a broad but
      shallow trochlea are distinctly ape-like, revealing capabilities for both
      rotation and withstanding eccentric loading in the knee. The navicular is
      characterized by features relating to a broad mid-tarsus and broad distal
      articulations for the cuneiforms. It also lacks a navicular tubercle as in Pongo.
      These features suggest that the foot was capable of a powerful grip on large
      supports, with an inversion/supination capability that would permit foot
      placement in a variety of positions. The morphology of the new phalanges,
      including evidence for a relatively large pollex, similarly suggests powerful
      grasping, consistent with prior evidence from the hallux and tarsus. The
      functional features of the new specimens permit refinement of previous
      interpretations of Sivapithecus positional capabilities. They suggest a locomotor
      repertoire dominated by pronograde activities and also such antipronograde
      activities as vertical climbing and clambering, but not by antipronograde
      suspensory activities as practiced by extant apes.

PMID- 12069508
TI  - Functional aspects of strepsirrhine lumbar vertebral bodies and spinous
      processes.
AB  - The relationship between form and function in the lumbar vertebral column has
      been well documented among platyrrhines and especially catarrhines, while
      functional studies of postcranial morphology among strepsirrhines have
      concentrated predominantly on the limbs. This morphometric study investigates
      biomechanically relevant attributes of the lumbar vertebral morphology of 20
      species of extant strepsirrhines. With this extensive sample, our goal is to
      address the influence of positional behavior on lumbar vertebral form while also
      assessing the effects of body size and phylogenetic history. The results reveal
      distinctions in lumbar vertebral morphology among strepsirrhines in functional
      association with their habitual postures and primary locomotor behaviors. In
      general, strepsirrhines that emphasize pronograde posture and quadrupedal
      locomotion combined with leaping (from a pronograde position) have the relatively
      longest lumbar regions and lumbar vertebral bodies, features promoting sagittal
      spinal flexibility. Indrids and galagonids that rely primarily on vertical
      clinging and leaping with orthograde posture share a relatively short (i.e.,
      stable and resistant to bending) lumbar region, although the length of individual
      lumbar vertebral bodies varies phylogenetically and possibly allometrically. The
      other two vertical clingers and leapers, Hapalemur and Lepilemur, more closely
      resemble the pronograde, quadrupedal taxa. The specialized, suspensory lorids
      have relatively short lumbar regions as well, but the lengths of their lumbar
      regions are influenced by body size, and Arctocebus has dramatically longer
      vertebral bodies than do the other lorids. Lumbar morphology among galagonids
      appears to reflect a strong phylogenetic signal superimposed on a functional one.
      In general, relative length of the spinous processes follows a positively
      allometric trend, although lorids (especially the larger-bodied forms) have
      relatively short spinous processes for their body size, in accordance with their
      positional repertoire. The results of the study broaden our understanding of
      postcranial adaptation in primates, while providing an extensive comparative
      database for interpreting vertebral morphology in fossil primates.

PMID- 12069509
TI  - Optimizing presurgical orthodontic planning by means of the transverse coordinate
      simulation system (TCSS).
AB  - INTRODUCTION: When planning bilateral sagittal split osteotomies according to
      Obwegeser and Dal Pont, inaccuracies in the presurgical prediction of the
      transverse osteotomy gaps may occur. This is due to limitations of plaster models
      when simulating surgery on an articulator. AIM: This paper demonstrates the
      transverse coordinate simulation system which allows presurgical prediction of
      the transverse discrepancy between the tooth bearing and the proximal segment
      after displacement, thus minimizing uncertainty for the surgeon. METHOD:
      Diagnostic landmarks (taken from lateral and frontal cephalograms) and clinical
      data describing mandibular dimensions are transferred to a two-dimensional
      coordinate diagram. A mandibular model is then constructed using the anterior
      arch form, the temporomandibular joint distance and the prospective incision
      pattern. RESULT: Movements in the horizontal plane and displacement of the three
      segments (two condylar and one mandibular arch segment) can be simulated and
      measured. CONCLUSION: Transverse coordinate simulation system effectively
      increases the accuracy of presurgical planning without additional CT data or
      three-dimensional jaw models. This technique may decrease the number of
      additional surgical manoeuvres resulting from unexpectedly wide transverse
      discrepancies at the osteotomy site, which often increase surgery time,
      necessitate additional bone grafting, and entail the risk of healing disturbances
      and of malrotation or dislocation of the condyle.

PMID- 12069510
TI  - The Graz implant supported pendulum, a technical note.
AB  - A new, immediately loadable palatal implant with rotational stability and an
      implant-supported pendulum for patients with dental class II dysgnathia and
      dental crowding is presented. In seven cases, the treatment goal of distalization
      of all upper molars without extraction of a single tooth was achieved within 8
      months.

PMID- 12069511
TI  - Oral Langerhans cell histiocytosis.
AB  - AIM: Our aim is to compare the different methods of treatment available for
      Langerhans cell histiocytosis (LCH) in the oral and maxillo-facial region. A
      classification based on clinical and immunohistochemical data is proposed and a
      grading for the severity of the disease is proposed. PATIENTS AND METHODS:
      Records and clinical data of 12 patients were evaluated retrospectively. The
      patients' ages ranged from 20 months to 47 years. Nine had manifestations in the
      maxillo-facial region, of which six had a single oral lesion only, with the three
      remaining patients having multiple lesions in this region. Three patients had
      lesions in the upper thorax in addition to their oral lesions. Eleven patients
      were treated surgically with one having been treated previously with steroid
      therapy. One patient had already been treated with chemotherapy. The longest
      follow-up was 16 years. Immunohistochemical stains for antigen-CD-1a, antigen-S
      100 and antigen-Ki-67 were performed. A proposal for staging the lesions in the
      oro-maxillo-facial region was made. The intensity of the antigen-Ki-67 stains was
      evaluated. RESULTS: Eleven patients exhibited no signs of recurrence whilst only
      one patient had a recurrence implying that surgical treatment was very effective
      in eradication and cure of the disorder. It is felt that the number of antigen-Ki
      67 positive cells is related to the activity of the disease. CONCLUSION:
      Langerhans cell histiocytosis should be treated surgically. Only in very severe
      cases should surgical treatment be complemented with either radio-therapy or
      chemotherapy. Especially in disseminated cases, chemotherapy would appear to
      improve the outcome. The antigen Ki-67 as proliferation marker is suggested as a
      grading parameter of this disease.

PMID- 12069512
TI  - Growth factor levels in platelet-rich plasma and correlations with donor age,
      sex, and platelet count.
AB  - INTRODUCTION: Platelet-rich plasma contains autologous thrombocyte growth factors
      and might be promising for acceleration of dentoalveolar bone regeneration. In
      this study, it was analysed for platelet counts and growth factor concentrations.
      MATERIAL AND METHOD: Platelet-rich plasma was isolated by discontinuous cell
      separation from 158 healthy men and 55 women aged 17-62 years. One hundred and
      fifteen specimens (stratified for age and gender of the donor) were analysed for
      growth factor concentrations and platelet count. RESULTS: The platelet count in
      platelet-rich plasma (1,407,640+/-320,100/microl) was 5 times higher than in
      donor blood (266,040+/-60,530/microl). Platelet-derived growth factor AB (117+/
      63 ng/ml), transforming growth factor (TGF) beta -1 (169+/-84 ng/ml), and insulin
      like growth factor (IGF) I (84+/-23 ng/ml) were found in large amounts, while
      platelet-derived growth factor (PDGF) BB (10+/-8 ng/ml) and transforming growth
      factor beta -2 (0.4+/-0.3 ng/ml) were found in small amounts only. The growth
      factor content was not well correlated with the platelet count in whole blood nor
      with the platelet-rich plasma (r(p)=0.35). No influence of gender or age on
      platelet count or growth factor concentrations was discovered (except IGF-I).
      CONCLUSIONS: While there was substantial variation in the growth factor content
      of platelet-rich plasma, the factors influencing this are still worthy of further
      investigation. Furthermore, a technique whereby the growth factor content could
      be rapidly assessed in platelet-rich plasma may be of therapeutic benefit.

PMID- 12069513
TI  - Tissue changes adjacent to titanium plates in patients.
AB  - INTRODUCTION: Titanium miniplates are widely used for osteosynthesis in
      maxillofacial surgery. Titanium is considered to be well tolerated but the long
      term effects of titanium retained within human tissues are unclear. AIMS: This
      study was designed to evaluate histomorphologically the soft tissues adjacent to
      titanium maxillofacial miniplates and screws in patients, and to determine the
      nature of pigmented, particulate debris found in the tissues. MATERIALS: Thirty
      five soft tissue specimens were excised from the tissues adjacent to titanium
      miniplates which had been in situ for between 1 month and 13 years. METHODS: All
      of the soft tissue specimens were prepared for examination under the light
      microscope. Four specimens were examined under the scanning electron microscope
      and the transmission electron microscope. Energy dispersive X-ray analysis (EDX)
      was used to confirm the elemental composition of the particles under
      investigation. RESULTS: All of the soft tissues showed fibrosis. Pigmented debris
      was present in 70% of the specimens and titanium was identified by EDX analysis.
      The debris was predominantly extra-cellular and was not associated with any
      inflammatory response or giant cell reaction. Fibroblasts were the predominant
      cell with small aggregates of lymphocytes and scattered macrophages. CONCLUSION:
      Titanium is apparently well tolerated for up to 13 years.

PMID- 12069514
TI  - Trigeminocardiac reflex: a unique case of recurrent asystole during bilateral
      trigeminal sensory root rhizotomy.
AB  - BACKGROUND: The trigeminocardiac reflex is the sudden-onset of dysrhythmia and
      hypotension during manipulation of any of the branches of the trigeminal nerve.
      The trigeminal nerve and cardioinhibitory vagus nerve constitute the afferent and
      efferent pathways in the reflex arc. The trigeminocardiac reflex has been
      reported to occur during craniofacial surgery, balloon-compression rhizolysis of
      the trigeminal ganglion, and tumour resection in the cerebellopontine angle.
      PATIENT & METHOD: A 2-year-old male patient with haemangioma near the sella
      turcica underwent rhizotomies of both sides of the dorsal sensory roots, of the
      trigeminal nerves for palliation of intractable trigeminal pain. RESULTS: In this
      report, we experienced two unexpected episodes of asystole after transection of
      the sensory roots of the trigeminal nerves. CONCLUSION: Sectioning of the
      intracranial dorsal sensory root of the trigeminal nerve provides clear evidence
      of the central role of the trigeminal nerve as the afferent pathway of the
      trigeminocardiac reflex arc.

PMID- 12069515
TI  - Combined modality treatment of oral and oropharyngeal cancer including
      neoadjuvant intraarterial cisplatin and radical surgery followed by concurrent
      radiation and chemotherapy with weekly docetaxel - three year results of a pilot
      study.
AB  - BACKGROUND: A new four-modality treatment of primary oral and oropharyngeal
      squamous cell carcinomas was evaluated with regard to feasibility, tolerance, and
      survival. PATIENTS AND METHODS: Seventy three operable patients (100%) with
      histologically proven untreated stage I to stage IV disease received at least one
      cycle of neoadjuvant intraarterial chemotherapy with 150 mg/m(2) cisplatin
      neutralized with sodium thiosulphate, followed by radical operation for the
      tumour with a simultaneous selective neck dissection (clinically negative neck),
      or modified radical neck dissection (nodal involvement), followed by adjuvant
      chemoradiation over 5 weeks (51.9 Gy, systemic docetaxel 25 mg/m(2), once every
      week). RESULTS: Ninety-six per cent of patients were operated on, 68% had
      postoperative radiation, 57% concomitant chemotherapy; 44% fulfilled the complete
      protocol. There have been 11 local or regional recurrences to date, three of
      which were treated by salvage surgery. Eighteen patients died, in nine of them
      death was tumour-related. Seventy five per cent lived after a median observation
      time of 33 months. Cumulative survival was 74% calculated for 4 years.
      CONCLUSION: The presented multimodality regimen proved feasible and showed better
      survival for the whole population and for all tumour stages when compared with
      the treatment-dependent prognosis index of the DOSAK (German-Austrian-Swiss
      Cooperative Group on tumours of the maxillofacial region).

PMID- 12069516
TI  - Valves in the subsidiary lymph trunks in the neck.
AB  - INTRODUCTION: The thoracic duct drains both lymph and chyle into the confluence
      of the great veins in the root of the neck. The venous termination of the duct is
      protected from retrograde flow of blood by valves. However, little attention has
      been focused on the presence or absence of valves in the subsidiary lymph trunks
      in the neck. AIMS: The aim of this study was to determine whether there are
      valves in the subsidiary lymphatic system in the neck. MATERIAL AND METHODS: The
      left side of the neck was explored in ten formalin-fixed cadavers. Subsidiary
      lymphatic trunks were carefully preserved for stereomicroscopic examination.
      RESULTS: Eight subsidiary trunks were identified comprising four jugular, two
      subclavian and two bronchomediastinal trunks. Both subclavian lymph trunks
      drained directly into a vein. A bicuspid ostial valve was present at the
      termination of the trunks. The bronchomediastinal and jugular trunks drained into
      the thoracic duct prior to its venous termination. Valvular structures were
      identified along the bronchomediastinal trunks and at their termination with the
      thoracic duct. No valves were identified in the jugular trunks. CONCLUSION: The
      absence of valves in the jugular lymph trunks is proposed as a possible
      contributory factor in the creation of chyle leaks following neck dissections.

PMID- 12069517
TI  - Importance-rating using the University of Washington quality of life
      questionnaire in patients treated by primary surgery for oral and oro-pharyngeal
      cancer.
AB  - BACKGROUND: There are now several validated and widely accepted head and neck
      cancer questionnaires. These record patients subjective levels of function and
      dysfunction, as well as symptoms related to their cancer and its treatment. One
      popular measure is the University of Washington head and neck cancer
      questionnaire (UW-QOL). Domain importance-ratings were added to the second
      version of the questionnaire, which was published in 1997. It is unique amongst
      head and neck cancer questionnaires in this respect. AIM: The purpose of the
      study was to evaluate UW-QOL with particular reference to domain importance
      rating. It was also the intention to investigate how the importance-ratings
      related to 'quality of life' and comment on the cumulative scoring of the
      questionnaire. METHODS: Forty-eight patients with previously untreated oral or
      oro-pharyngeal cancer were recruited. All were treated by primary surgery.
      Questionnaires were completed pre-operatively, 6 months and 1 year post
      operatively. RESULTS: This study demonstrates a wide variation in importance
      ratings. Both pre- and post-treatment there was a general lack of correlation
      between importance-rating and domain scores. At all time points, patients tended
      to rate speech, chewing and swallowing as more important than the other UW-QOL
      domains. The cumulative UW-QOL score correlated strongly with the new single item
      QOL question. CONCLUSION: It remains unclear how best to incorporate importance
      ratings into a single UW-QOL total score. However, for individual patients they
      can assist in setting priorities in treatment strategies.

PMID- 12069519
TI  - Respiratory syncytial virus: reverse genetics and vaccine strategies.

PMID- 12069520
TI  - Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during
      infected cell death.
AB  - V-CATH, a cathepsin L-like cysteine protease encoded by the baculovirus
      Autographa californica M nucleopolyhedrovirus, has been shown to play an
      essential role in host liquefaction. Similar to cellular cathepsin L, V-CATH is
      synthesized as an inactive proenzyme and is activated by cleavage of the
      propeptide. Previous studies indicated that removal of the propeptide was rapid,
      occurring as soon as the protein could be detected by Western blot, 22 h
      postinfection. We found, however, that these results reflected artifactual
      processing of the proenzyme. When the protease inhibitor E-64 was used to prevent
      this aberration, we found that proV-CATH accumulated in infected cells and
      activation did not begin until the onset of cell death, at approximately 80 h
      postinfection. Western blot analysis of fractions of live and dead cells isolated
      by fluorescence-activated cell sorting revealed that mature V-CATH was found only
      in dead cells. The regulation of activation of proV-CATH, therefore, was quite
      different from that of cellular cathepsins. Acridine orange staining revealed
      that lysosome integrity was lost in dead cells, an occurrence that could lead to
      the activation of proV-CATH by lysosomal proteases.

PMID- 12069521
TI  - Construction and characterization of subgenomic replicons of New York strain of
      West Nile virus.
AB  - The lineage I strain of West Nile virus (WNV) frequently causes human epidemics,
      including the recent outbreak in North America (Lanciotti et al., 1999, Science
      286:2333-2337). As an initial step in studying the replication and pathogenesis
      of WNV, we constructed several cDNA clones of a WNV replicon derived from an
      epidemic strain (lineage I) isolated from the epicenter of New York City in the
      year 2000. Replicon RNAs were in vitro transcribed from cDNA plasmids and
      transfected into BHK-21 cells. RNA replication in transfected cells was monitored
      by immunofluorescence analysis (IFA) and 5' nuclease real-time RT-PCR (TaqMan).
      The replicon RNAs contained large in-frame deletions (greater than 92%) of the C
      prM-E structural region yet still replicated efficiently in BHK-21 cells. 5'
      nuclease real-time RT-PCR showed that a great excess of plus-sense replicon RNA
      over the minus-sense RNA was synthesized in transfected cells. Replication
      efficiency decreased upon insertion of a green fluorescent protein (GFP) reporter
      gene driven by an internal ribosomal entry site (IRES) in the upstream end of the
      3' untranslated region of the replicon. Strong GFP expression was detected in
      cells transfected with a replicon containing IRES-GFP positioned in the plus
      sense orientation. IFA showed that GFP and viral proteins were exclusively
      coexpressed in transfected cells. In contrast, no GFP fluorescence was observed
      in cells transfected with a replicon containing IRES-GFP positioned in the minus
      sense orientation, despite high levels of synthesis of viral proteins and RNA in
      the cells. Substitution of the GFP gene in the plus-sense GFP replicon with the
      neomycin phosphotransferase gene allowed selection of geneticin-resistant cells
      in which WNV replicons persistently replicated without apparent cytopathic
      effect. These results suggest that WNV replicons may serve as a noncytopathic RNA
      virus expression system and should provide a valuable tool to study WNV
      replication.

PMID- 12069522
TI  - In the virion, the 11-amino-acid peptide cofactor pVIc is covalently linked to
      the adenovirus proteinase.
AB  - Previously, the adenovirus proteinase (AVP) had been shown to be stimulated by an
      11-amino-acid cofactor pVIc; the crystal structure of an AVP-pVIc complex formed
      in vitro reveals a disulfide bond between AVP and pVIc. However, that disulfide
      bond was recently shown not to be required for maximal stimulation of enzyme
      activity by pVIc in vitro. Is the disulfide bond physiologically relevant or is
      it an artifact that arose in the crystallization of the complex? Here we show
      that a disulfide bond between AVP and pVIc is physiologically relevant, because
      in the virus particle AVP is linked to pVIc via a disulfide bond. This is also
      the first experimental proof that AVP interacts in vivo with one of its
      cofactors, all of which were discovered and characterized in vitro. A rationale
      as to why this apparently unnecessary disulfide bond between AVP and pVIc forms
      in the virus particle is presented.

PMID- 12069523
TI  - Birnavirus VP1 proteins form a distinct subgroup of RNA-dependent RNA polymerases
      lacking a GDD motif.
AB  - We have cloned and characterized the Drosophila X virus (DXV) genome segment B
      and its encoded VP1, the putative RNA-dependent RNA polymerase (RdRp) present in
      the virion. The 2991-bp open reading frame encodes the largest birnavirus VP1 at
      977 aa, with a calculated M(r) of 112.8 kDa. As with the VP1 proteins of the type
      species of the other two genera in the family Birnaviridae, namely, infectious
      pancreatic necrosis virus (genus Aquabirnavirus) and infectious bursal disease
      virus (genus Avibirnavirus), the DXV (genus Entomobirnavirus) VP1 protein
      contains a consensus GTP-binding site and appears to possess self-guanylylation
      activity. All of the birnavirus VP1 proteins contain conserved RdRp motifs that
      reside in the catalytic "palm" domain of all classes of polymerases. However, the
      birnavirus RdRps lack the highly conserved Gly-Asp-Asp (GDD) sequence, a
      component of the proposed catalytic site of this enzyme family that exists in the
      conserved motif VI of the palm domain of other RdRps. All three birnavirus RdRps
      do contain downstream DD motifs that could function as part of the catalytic
      triad. These motifs are, however, located in spatially distinct regions of the
      various birnavirus VP1 proteins. These results suggest that the VP1 proteins of
      birnaviruses form a defined subgroup of polymerases that either are lacking the
      conserved RdRp motif VI or have repositioned this motif to different structural
      regions.

PMID- 12069524
TI  - The N-terminal domain of the phosphoprotein of Morbilliviruses belongs to the
      natively unfolded class of proteins.
AB  - We report the bacterial expression, purification, and characterization of the N
      terminal domain (PNT) of the measles virus phosphoprotein. Using nuclear magnetic
      resonance, circular dichroism, gel filtration, and light scattering, we show that
      PNT is not structured in solution. We show by two complementary computational
      approaches that PNT belongs to the recently described class of natively unfolded
      proteins, further confirming its reported similarity with acidic activation
      domains of cellular transcription factors. We extend these results to the N
      terminal domains of other Morbillivirus phosphoproteins and to the corresponding
      protein W of Sendai virus, a Paramyxovirus. Unstructured proteins may undergo
      some degree of folding upon binding to their partners, a process termed "induced
      folding." Using limited proteolysis in the presence of trifluoroethanol, we
      identified residues 27 to 38 as a putative secondary structure element of PNT
      arising upon induced folding.

PMID- 12069525
TI  - Analysis of minimal promoter sequences for plus-strand synthesis by the Cucumber
      necrosis virus RNA-dependent RNA polymerase.
AB  - Tombusviruses are small, plus-sense, single-stranded RNA viruses of plants. A
      partially purified RNA-dependent RNA polymerase (RdRp) preparation of Cucumber
      necrosis virus (CNV), which is capable of de novo initiation of complementary RNA
      synthesis from either plus-strand or minus-strand templates, was used to dissect
      minimal promoter sequences for tombusviruses and their defective interfering (DI)
      RNAs. In vitro RdRp assay revealed that the core plus-strand initiation promoter
      included only the 3'-terminal 11 nucleotides. A hypothetical promoter-like
      sequence, which has been termed consensus sequence by Wu and White (1998, J.
      Virol. 72, 9897-9905), is recognized less efficiently by the CNV RdRp than the
      core plus-strand initiation promoter. The CNV RdRp can efficiently recognize the
      core plus-strand initiation promoter for a satellite RNA associated with the
      distantly related Turnip crinkle virus, while artificial AU- or GC-rich 3'
      terminal sequences make poor templates in the in vitro assays. Comparison of the
      "strength" of minimal plus-strand and minus-strand initiation promoters reveals
      that the latter is almost twice as efficient in promoting complementary RNA
      synthesis. Template competition experiments, however, suggest that the minimal
      plus-strand initiation promoter makes an RNA template more competitive than the
      minimal minus-strand initiation promoter. Taken together, these results
      demonstrate that promoter recognition by the tombusvirus RdRp requires only short
      sequences present at the 3' end of templates.

PMID- 12069526
TI  - Internal initiation by the cucumber necrosis virus RNA-dependent RNA polymerase
      is facilitated by promoter-like sequences.
AB  - Tombusviruses, small positive sense RNA viruses of plants, are replicated by the
      viral-coded RNA-dependent RNA polymerase (RdRp) in infected cells. An unusual
      feature of the tombusvirus RdRp that is partially purified from cucumber necrosis
      virus (CNV)-infected plants is the ability to initiate complementary RNA
      synthesis from several internal positions on minus-strand templates derived from
      DI RNAs ( Nagy and Pogany, 2000 ). In this study, we used template deletion,
      mutagenesis, and oligo-based inhibition of RNA synthesis to map the internal
      initiation sites observed with the in vitro CNV RdRp system. Comparing sequences
      around the internal initiation sites reveals that they have either (i) similar
      sequences to the core minus-strand initiation promoter; or (ii) similar
      structures to the core plus-strand initiation promoter. In addition, we find
      similarities among the internal initiation sites and the subgenomic RNA
      initiation sites. These similarities suggest that the mechanism of internal
      initiation is similar to initiation from the terminal core promoters or the
      putative subgenomic promoter sequences. We propose that internal initiation on
      full-length RNA templates may be important in defective interfering (DI) RNA
      formation/evolution by producing intermediate templates for RNA recombination in
      tombusviruses. This may explain why tombusviruses are frequently associated with
      DI RNAs.

PMID- 12069528
TI  - Morphology of Marburg virus NP-RNA.
AB  - When Marburg virus (MBGV) nucleoprotein (NP) is expressed in insect cells, it
      binds to cellular RNA and forms NP-RNA complexes such as insect cell-expressed
      nucleoproteins from other nonsegmented negative-strand RNA viruses. Recombinant
      MBGV NP-RNA forms loose coils that resemble rabies virus N-RNA. MBGV NP monomers
      are rods that are spaced along the coil similar to the nucleoprotein monomers of
      the rabies virus N-RNA. High salt treatment induces tight coiling of the MBGV NP
      RNA, again a characteristic observed for other nonsegmented negative-strand virus
      N-RNAs. Electron microscopy of fixed Marburg virus particles shows that the viral
      nucleocapsid has a smaller diameter than the free, recombinant NP-RNA. This
      difference in helical parameters could be caused by the interaction of other
      viral proteins with the NP-RNA. A similar but opposite phenomenon is observed for
      rhabdovirus nucleocapsids that are condensed by the viral matrix protein upon
      which they acquire a larger diameter. Finally, there appears to be an extensive
      and regular protein scaffold between the viral nucleocapsid and the membrane that
      seems not to exist in the other negative-strand RNA viruses.

PMID- 12069527
TI  - Cloning, expression, and characterization of avian reovirus guanylyltransferase.
AB  - We have cloned and sequenced the L3 genome segment of avian reovirus strain 1733,
      which specifies the viral guanylyltransferase protein, lambdaC. The L3 gene is
      3907 nucleotides long and encodes, in a single large open-reading frame, a
      polypeptide of 1285 amino acid residues, with a calculated M(r) of 142.2 kDa.
      Expression of this gene in a baculovirus/insect cell system produced a
      recombinant protein that comigrated with reovirion lambdaC and reacted with anti
      reovirus polyclonal serum in a Western blot assay. Incubation of recombinant
      lambdaC with GTP led to the formation GMP-lambdaC complex via a phosphoamide
      linkage. Interestingly, a 42-kDa amino-terminal proteolytic fragment of
      recombinant lambdaC protein also exhibited autoguanylylation activity,
      demonstrating both that this fragment is necessary and sufficient for
      autoguanylylation activity and that the 100-kDa complementary fragment is
      expendable for that activity. Comparison of the deduced amino acid sequence of
      protein lambdaC with those of the mammalian and grass carp reovirus
      guanylyltransferases revealed that only two of eight lysine residues within the
      amino-terminal 42-kDa region are conserved. Interestingly, these two lysines
      match with the lysine residues in the mammalian reovirus capping enzyme proposed
      to be essential for autoguanylylation activity. Our alignment analysis also
      showed that the S-adenosyl-l-methionine-binding pocket previously detected in the
      mammalian reovirus capping enzyme is fully conserved in its avian and grass carp
      reovirus counterparts, suggesting that all three enzymes have methylase activity.

PMID- 12069529
TI  - Complete genomic sequence of bacteriophage ul36: demonstration of phage
      heterogeneity within the P335 quasi-species of lactococcal phages.
AB  - The complete genomic sequence of the Lactococcus lactis virulent phage ul36
      belonging to P335 lactococcal phage species was determined and analyzed. The
      genomic sequence of this lactococcal phage contained 36,798 bp with an overall
      G+C content of 35.8 mol %. Fifty-nine open reading frames (ORFs) of more than 40
      codons were found. N-terminal sequencing of phage structural proteins as well as
      bioinformatic analysis led to the attribution of a function to 24 ORFs (41%). A
      lysogeny module was found within the genome of this virulent phage. The putative
      integrase gene seems to be the product of a horizontal transfer because it is
      more closely related to Streptococcus pyogenes phages than it is to L. lactis
      phages. Comparative genome analysis with six complete genomes of temperate P335
      like phages confirmed the heterogeneity among phages of P335 species. A dUTPase
      gene is the only conserved gene among all P335 phages analyzed as well as the
      phage BK5-T. A genetic relationship between P335 phages and the phage-type of the
      BK5-T species was established. Thus, we proposed that phage BK5-T be included
      within the P335 species and thereby reducing the number of lactococcal phage
      species to 11.

PMID- 12069530
TI  - RNA helicase activity of the plant virus movement proteins encoded by the first
      gene of the triple gene block.
AB  - Cell-to-cell and long-distance transport of some plant viruses requires
      coordinated action of three movement proteins encoded by triple gene block (TGB).
      The largest of TGB proteins, TGBp1, is a member of the superfamily I of DNA/RNA
      helicases and possesses a set of conserved helicase sequence motifs necessary for
      virus movement. A recombinant His-tagged form of TGBp1 of two hordeiviruses and
      potato virus X, a potexvirus, produced in Escherichia coli had unwinding activity
      on a partially duplexed RNA, but not DNA substrate. The helicase activity of
      these proteins was dependent on Mg2+ and ATP. The isolated C-terminal half of the
      PSLV TGBp1 retaining all helicase motifs was also able to unwind RNA duplex.

PMID- 12069532
TI  - Mechanisms of protection induced by attenuated simian immunodeficiency virus.
AB  - To determine whether attenuated simian immunodeficiency virus (SIV) vaccines
      confer protection against superinfection via secondary cellular immune responses,
      we searched for markers of immune activation following rechallenge. Productive
      infection with either attenuated SIVmacC8 or wild-type SIVmacJ5 resulted in a
      transient increase in T-lymphocyte CD25 and Mafa-DR expression. A pronounced
      increase in the frequency of FAS+ CD8+ lymphocytes was observed following
      SIVmacJ5 infection only. A transient increase in lymphocytes positive for
      intracellular IFN-gamma and IL-4 was observed following primary infection with
      either virus. In contrast, lymphocytes positive for intracellular IL-2 were
      reduced. Following SIVmacJ5 challenge of SIVmacC8-infected vaccinees, no evidence
      of detectable superinfection was obtained. Rechallenge of vaccinees did not alter
      the frequency of activated peripheral T-lymphocytes, perturb cytokine profiles,
      or generate an anamnestic antibody response. These data do not support the
      hypothesis that protection conferred by live attenuated SIV is mediated by the
      induction of vigorous T-cell responses upon rechallenge.

PMID- 12069531
TI  - The role of endothelial cell-derived inflammatory and vasoactive mediators in the
      pathogenesis of bluetongue.
AB  - Bluetongue is an insect-transmitted disease of sheep and wild ruminants that is
      caused by bluetongue virus (BTV). Cattle are asymptomatic reservoir hosts of BTV.
      Infection of lung microvascular endothelial cells (ECs) is central to the
      pathogenesis of BTV infection of both sheep and cattle, but it is uncertain as to
      why sheep are highly susceptible to BTV-induced microvascular injury, whereas
      cattle are not. Thus, to better characterize the pathogenesis of bluetongue, the
      transcription of genes encoding a variety of vasoactive and inflammatory
      mediators was quantitated in primary ovine lung microvascular ECs (OLmVECs)
      exposed to BTV and/or inflammatory mediators. BTV infection of OLmVECs increased
      the transcription of genes encoding interleukin- (IL) 1 and IL-8, but less so IL
      6, cyclooxygenase-2, and inducible nitric oxide synthase. In contrast, we
      previously have shown that transcription of genes encoding all of these same
      mediators is markedly increased in BTV-infected bovine lung microvascular ECs and
      that BTV-infected bovine ECs produce substantially greater quantities of
      prostacyclin than do sheep ECs. Thus, sheep and cattle were experimentally
      infected with BTV to further investigate the role of EC-derived vasoactive
      mediators in the pathogenesis of bluetongue. The ratio of thromboxane to
      prostacyclin increased during BTV infection of both sheep and cattle, but was
      significantly greater in sheep (P = 0.001). Increases in the ratio of thromboxane
      to prostacyclin, indicative of enhanced coagulation, coincided with the
      occurrence of clinical manifestations of bluetongue in BTV-infected sheep. The
      data suggest that inherent species-specific differences in the production and
      activities of EC-derived mediators contribute to the sensitivity of sheep to BTV
      induced microvascular injury.

PMID- 12069533
TI  - Inborn errors of metabolism.

PMID- 12069534
TI  - Clinical approach to inherited metabolic disorders in neonates: an overview.
AB  - There are almost one hundred inborn errors of metabolism which can start in the
      neonatal period, but less than 20 are amenable to treatment. In general, an
      extremely evocative clinical setting is the course of a full-term baby born after
      normal pregnancy and delivery who, after an initial symptom-free period
      deteriorates relentlessly for no apparent reason and does not respond to
      symptomatic therapy. Investigations routinely performed in all sick neonates
      yield normal results. Emergency treatment must be undertaken in parallel with
      investigations. Five main presentations can be observed: a neurologic
      deterioration 'intoxication' type mostly suggests maple syrup urine disease,
      methylmalonic, propionic, isovaleric acidaemias and urea cycle disorders.
      Isolated seizures is the revealing symptom of pyridoxine-responsive and folinic
      acid responsive seizures. A jaundice or a liver failure suggest galactosaemia,
      fructosaemia, tyrosinaemia type I (after 3 weeks), phosphomannoisomerase
      deficiency or bile acid synthesis defects. Cardiac failure and heartbeat
      disorders should first suggest mitochondrial fatty acid oxidation (FAO)
      disorders. Persistent hypoglycaemia is the presenting sign of
      glyco/gluconeogeneis defects, hyperinsulinism and FAO disorders. The first line
      investigation relies upon the collection at the same time of a few samples
      including blood gases electrolytes, prothrombin time, transaminases, ammonia and
      lactic acid, and the search for ketonuria. The storage of plasma, urine and blood
      (on filter paper) is an important element in the diagnosis. The utilization of
      these samples should be carefully planned after taking advice from specialists in
      inborn errors.

PMID- 12069535
TI  - Management and emergency treatments of neonates with a suspicion of inborn errors
      of metabolism.
AB  - During the neonatal period, inborn errors of metabolism mostly present with an
      overwhelming illness that requires prompt diagnosis and both supportive and
      specific treatments. The most frequent situations are due to branched-chain
      organic acidurias that present with ketoacidosis and urea cycle defects that are
      characterized by hyperammonaemia. During both situations, toxin removal
      procedures and nutritional support with a free-protein and high-energy diet are
      pivotal treatments. In patients presenting with hypoglycaemia blood glucose
      levels must be corrected. Progress following glucose provision is useful in
      recognizing the disorders that are mainly implicated. Hyperinsulinism requires
      high-glucose infusion. Glycogen storage diseases and gluconeogenesis defects are
      easily treated with a permanent glucose provision while hypoglycaemias quickly
      recur. In patients with galactosaemia, hereditary fructose intolerance or
      tyrosinaemia type I, the presentation is dominated by a liver failure requiring
      galactose and fructose exclusion associated with a low-protein diet. Many
      patients with beta-oxidation defects may present with hypoglycaemia that is
      usually easily corrected. The precise diagnosis can be easily missed in those
      patients that do well in the following weeks but may develop cardiac failure,
      arrhythmia and/or liver failure. Patients presenting with intractable
      convulsions, vitamin responsiveness to biotin, pyridoxine and folate must be
      considered.

PMID- 12069536
TI  - Urea cycle disorders.
AB  - Most patients with urea cycle disorders who present as neonates, do so with
      deteriorating feeding, drowsiness and tachypnoea, following a short initial
      period when they appear well. The plasma ammonia should be measured at the same
      time as the septic screen in such patients. Ammonia levels above 200 micromol/l
      are usually caused by inherited metabolic diseases and it is essential to make a
      diagnosis for genetic counselling, even if the patients die. The aim of treatment
      is to lower the ammonia concentrations as fast as possible. Sodium benzoate,
      sodium phenylbutyrate and arginine can exploit alternative pathways for the
      elimination of nitrogen but haemodialysis or haemofiltration should be instituted
      if ammonia concentrations are >500 micromol/l or if they do not fall promptly.
      Long-term management involves drugs, dietary protein restriction and use of an
      emergency regimen during illness. Severe hyperammonaemia is usually associated
      with irreversible neurological damage, particularly if levels have been above 800
      micromol/l for >24 hours, and the option of withdrawing treatment should be
      discussed with the family.

PMID- 12069537
TI  - Inherited disorders of mitochondrial fatty acid oxidation: a new responsibility
      for the neonatologist.
AB  - The disorders of mitochondrial fat oxidation present clinically with three major
      clinical phenotypes: hypoketotic hypoglycemia, cardiomyopathy, and myopathy.
      Although these features can present together in some of the disorders, one will
      be the dominant clinical problem. This review will describe these clinical
      phenotypes while addressing the diagnostic value of various clinical and
      laboratory studies which are often used for making these diagnoses. With
      knowledge of the clinical presentation, these diagnoses can often be made very
      rapidly and at relatively low cost by more specific laboratory tests. The
      increasing availability of expanded newborn screening by tandem mass spectrometry
      as well as prenatal diagnosis for these often fatal disorders now provides the
      opportunity for pre-symptomatic diagnosis. The neonatologist is now in the unique
      position of identifying these inherited disorders prior to or during severe
      symptom onset and has the earliest opportunity to provide successful treatment
      intervention.

PMID- 12069538
TI  - Inborn errors presenting with liver dysfunction.
AB  - In neonates, inborn errors of metabolism can produce all the major signs of liver
      dysfunction - jaundice, coagulopathy, hepatomegaly, splenomegaly, ascites and
      encephalopathy. The significance of encephalopathy in the neonate is different
      from that in older patients; it is usually due to a specific abnormality such as
      hypoglycaemia rather than being a non-specific indicator of liver failure.
      Attention is focused on five neonatal presentations: unconjugated
      hyperbilirubinaemia, cholestatic jaundice with otherwise good liver function,
      severe liver dysfunction (jaundice, coagulopathy persisting after vitamin K, and
      ascites), hepatomegaly with hypotonia+/- cardiomyopathy; and hepatosplenomegaly.
      The metabolic disorders presenting in these ways are listed alongside specific
      clinical features that can aid differential diagnosis and tests that can be used
      to confirm or refute the diagnosis. Diagnosis is important because treatment can
      be dramatically effective, e.g. withdrawal of galactose in galactosaemia. Even
      when treatment is not effective it is often possible to offer prenatal diagnosis
      for future pregnancies.

PMID- 12069539
TI  - Branched-chain organic acidurias.
AB  - Branched chain organic acidurias are a group of disorders that result from an
      abnormality of specific enzymes involving the catabolism of branched chain amino
      acids (leucine, isoleucine, valine). Maple syrup urine disease (MSUD), isovaleric
      acidaemia (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA)
      represent the most commonly encountered abnormal organic acidurias. All these
      four disorders present in neonates as a neurologic distress of the intoxication
      type with either ketosis or ketoacidosis and hyperammonaemia. There is a free
      interval between birth and clinical symptoms. MMA, PA and IVA present with a
      severe dehydration, leuconeutropenia and thrombopenia which can mimic sepsis. All
      these disorders can be diagnosed by identifying acylcarnitine and other organic
      acid compounds in plasma and urine by gas chromatography mass spectrometry or
      tandem MS-MS. These disorders are amenable to treatment by removing toxic
      compounds and by using special diets and carnitine.

PMID- 12069540
TI  - Lysosomal disorders.
AB  - Although most lysosomal storage disorders present in infancy or early childhood
      with a progressive condition often associated with dysmorphism, considerable
      genetic heterogeneity exists resulting in a range of illnesses that can include a
      dramatic neonatal presentation. Whilst some conditions present with a
      characteristic neonatal phenotype (e.g. Niemann-Pick disease type C), the
      remainder present in a nonspecific way often with non-immune hydrops fetalis.
      Diagnosis can be helped by appropriate radiological studies and, in some
      patients, evidence of the storage phenomena can be seen in peripheral blood
      smears or bone marrow aspirates. Unfortunately, for the majority of affected
      patients no effective, curative, treatment is possible. New developments in
      therapy including enzyme replacement therapy and substrate deprivation may
      improve prognosis in some disorders. It is important to establish an accurate
      diagnosis, as prenatal testing can then be offered in future pregnancies.

PMID- 12069541
TI  - Peroxisomal disorders.
AB  - Peroxisomes are subcellular organelles catalyzing a number of indispensable
      functions in cellular metabolism. The importance of peroxisomes is stressed by
      the existence of an expanding number of genetic diseases in which there is an
      impairment of one or more peroxisomal functions. The prototype of this group of
      diseases is the cerebro-hepato-renal syndrome of Zellweger (ZS), first described
      as a familial syndrome of multiple congenital defects in 1964. ZS is
      characterized by the presence of dysmorphias and polymalformative syndrome,
      severe neurologic abnormalities including neurosensory defects and hepato
      intestinal dysfunction with failure to thrive and usually early death. Other
      peroxisomal disorders share some of these symptoms, but with varying degrees of
      organ involvement, severity of dysfunction and duration of survival. This paper
      provides an overview of the peroxisomal disorders including their clinical,
      biochemical and molecular characteristics with particular emphasis on the
      clinical presentation in neonates.

PMID- 12069542
TI  - Persistent hyperinsulinaemic hypoglycaemia.
AB  - Congenital hyperinsulinism (CI) is the most important cause of hypoglycaemia in
      early infancy. The inappropriate oversecretion of insulin is responsible for
      profound hypoglycaemias which require aggressive treatment to prevent severe and
      irreversible brain damage. Hypoglycaemia have a neonatal or infancy onset.
      Medical treatment with diazoxide is first used to treat CI, but patients who are
      medically resistant (mostly of neonatal-onset) require pancreatectomy. CI is a
      heterogeneous disorder with two histopathological lesions, diffuse and focal
      which are clinically indistinguishable. Only diazoxide-sensitive neonates should
      be orientated to transient hyperinsulinism or hyperinsulinism-hyperammonemia
      syndrome. Focal CI is characterized by a sporadic somatic islet-cell hyperplasia.
      Diffuse CI corresponds to a functional abnormality of insulin secretion in the
      whole pancreas and involves several genes with different transmissions. The
      knowledge of both focal and diffuse lesions is very important. Focal lesions are
      effectively treated by limited pancreatic resection while diffuse lesions which
      are unresponsive to drug or dietary treatment require extensive pancreatectomy
      with high risk of diabetes mellitus.

PMID- 12069543
TI  - Molecular phylogeny of symbiotic dinoflagellates inferred from partial
      chloroplast large subunit (23S)-rDNA sequences.
AB  - Symbiotic associations between invertebrates and dinoflagellates of the genus
      Symbiodinium are a common occurrence in marine environments. However, despite our
      extensive knowledge concerning the physiological contributions of these algae to
      their symbiotic partners, our understanding of zooxanthella phylogenetics is
      still in its early stages. In the past 10 years, studies of Symbiodinium
      phylogenetics have relied solely on nuclear ribosomal (rDNA) genes. To date,
      organellar DNA sequences have not been employed to infer phylogenies for this
      genus of symbiotic dinoflagellates. We address this by presenting the first
      Symbiodinium phylogeny based on chloroplast (cp) large subunit (23S)-rDNA
      sequences. Cp23S-rDNA Domain V sequences were determined for 35 dinoflagellate
      cultures isolated from a range of invertebrate host species and geographical
      locations. Symbiodinium phylogenies inferred from cp23S-rDNA produced topologies
      that were not statistically different from those generated from nuclear rDNA,
      providing the first independent evidence supporting the published major clades of
      Symbiodinium. In addition, comparisons of sequence dissimilarity indicated that
      cp23S-rDNA Domain V evolves 9-30 times faster than the V1-V4 regions of nuclear
      small subunit (n18S)-rDNA, 1-7 times as fast as the D1-D3 regions of nuclear
      large subunit (n28S)-rDNA, and 0.27-2.25 times that of the internal transcribed
      spacer (ITS)-rDNA region. Our data suggested that cp23S-rDNA Domain V will prove
      to be a useful molecule for exploring Symbiodinium phylogenetics.

PMID- 12069544
TI  - Three nonorthologous ITS1 types are present in a polypore fungus Trichaptum
      abietinum.
AB  - To explore phylogenetic relationships of Trichaptum species, internal transcribed
      spacer (ITS) regions of nuclear ribosomal DNAs were sequenced and analyzed. Gene
      trees from ITS1 and ITS2 sequences showed striking discrepancy in relationships
      of eight T. abietinum strains. All strains of T. abietinum had a single
      orthologous ITS2 type, but there were three paralogous types in the ITS1 region,
      which were designated Types I, II, and III. PCR amplification tests using type
      specific primers showed that Types I and II are present in all strains of T.
      abietinum. The results suggest that gene duplication of the ancestral ITS1 region
      might have occurred prior to evolutionary radiation of Trichaptum and both types
      have been maintained in Trichaptum. However, Type III was amplified only in three
      T. abietinum strains collected from Korea, indicating that a new local geographic
      subtype has arisen in Korean strains.

PMID- 12069545
TI  - Phylogeny of the genus Apodemus with a special emphasis on the subgenus Sylvaemus
      using the nuclear IRBP gene and two mitochondrial markers: cytochrome b and 12S
      rRNA.
AB  - Phylogenetic relationships among 17 extant species of Murinae, with special
      reference to the genus Apodemus, were investigated using sequence data from the
      nuclear protein-coding gene IRBP (15 species) and the two mitochondrial genes
      cytochrome b and 12S rRNA (17 species). The analysis of the three genes does not
      resolve the relationships between Mus, Apodemus, and Rattus but separates
      Micromys from these three genera. The analysis of the two mitochondrial regions
      supported an association between Apodemus and Tokudaia and indicated that these
      two genera are more closely related to Mus than to Rattus or Micromys. Within
      Apodemus, the mitochondrial data sets indicated that 8 of the 9 species analyzed
      can be sorted into two main groups: an Apodemus group, with A. agrarius, semotus,
      and peninsulae, and a Sylvaemus group, with uralensis, flavicollis, alpicola,
      sylvaticus, and hermonensis. The position of Apodemus mystacinus is ambiguous and
      might be either included in Sylvaemus or considered a distinct subgenus,
      Karstomys, more closely related to Sylvaemus than to Apodemus. Estimation of the
      divergence time for these taxa suggests a separation between 7 and 8 My ago for
      the three groups (mystacinus and the two subgenera Apodemus and Sylvaemus).
      Within each subgenus, divergence times are between 5.4 and 6 My for Apodemus and
      between 2.2 and 3.5 My for Sylvaemus and mystacinus.

PMID- 12069546
TI  - Analysis of the mitochondrial 12S rRNA gene supports a two-clade hypothesis of
      the evolutionary history of scleractinian corals.
AB  - Scleractinian corals have long been assumed to be a monophyletic group
      characterized by the possession of an aragonite skeleton. Analyses of skeletal
      morphology and molecular data have shown conflicting patterns of suborder and
      family relationships of scleractinian corals, because molecular data suggest that
      the scleractinian skeleton could have evolved as many as four times. Here we
      describe patterns of molecular evolution in a segment of the mitochondrial (mt)
      12S ribosomal RNA gene from 28 species of scleractinian corals and use this gene
      to infer the evolutionary history of scleractinians. We show that the sequences
      obtained fall into two distinct clades, defined by PCR product length. Base
      composition among taxa did not differ significantly when the two clades were
      considered separately or as a single group. Overall, transition substitutions
      accumulated more quickly relative to transversion substitutions within both
      clades. Spatial patterns of substitutions along the 12S rRNA gene and likelihood
      ratio tests of divergence rates both indicate that the 12S rRNA gene of each
      clade evolved under different constraints. Phylogenetic analyses using mt 12S
      rRNA gene data do not support the current view of scleractinian phylogeny based
      upon skeletal morphology and fossil records. Rather, the two-clade hypothesis
      derived from the mt 16S ribosomal gene is supported.

PMID- 12069547
TI  - The perils of using host relationships in parasite taxonomy: phylogeny of the
      Degeeriella complex.
AB  - The taxonomy of lice (Insecta: Phthiraptera) is often heavily influenced by host
      taxonomy. The use of host information to define genera of avian lice in the
      widespread Degeeriella complex has been prevalent but has created problems.
      Several workers have suggested that genera defined on the basis of host
      association are not monophyletic. We used sequences of nuclear (elongation factor
      1alpha) and mitochondrial (cytochrome oxidase I) genes to test the monophyly of
      several genera in the Degeeriella complex. Parsimony and likelihood analyses of
      these data indicated that many genera in the Degeeriella complex are not
      monophyletic, such that species occurring on the same host groups do not form
      monophyletic groups. Biological features of hosts (including predaceous habits,
      brood parasitism, and hole nesting) for species in the Degeeriella complex likely
      provide opportunities for switching of lice between host groups. In addition,
      dispersal of lice via phoresy on hippoboscid flies also likely provides
      opportunities for host switching in the Degeeriella complex. This study indicates
      that the overuse of host taxonomy in louse taxonomy can result in classifications
      that do not reflect phylogenetic history.

PMID- 12069548
TI  - Isolates of Microbotryum violaceum from North American host species are
      phylogenetically distinct from their European host-derived counterparts.
AB  - Microbotryum violaceum is a basidiomycete that infects the anthers of its
      Caryophyllaceae host species. Individual fungal isolates are host limited, though
      they are not morphologically distinct. This study used variable regions of the
      highly conserved gamma-tubulin, beta-tubulin, and ribosomal RNA-encoding genes to
      determine the relationships among M. violaceum fungal isolates from different
      host species and different geographical locations. Phylogenetic trees from intron
      nucleotide sequences in two protein-coding genes were compared to trees produced
      from internal transcribed spacers (ITS) of rDNA. Phylogenetic analyses suggested
      that there are two clades, one from North America and one from Europe. Isolates
      from both clades grouped according to host species, although in some analyses
      isolates from closely related host species were placed together. These results
      are consistent with the view that M. violaceum has experienced cospeciation with
      its hosts.

PMID- 12069549
TI  - Extraordinary haplotype diversity in haplodiploid inbreeders: phylogenetics and
      evolution of the bark beetle genus Coccotrypes.
AB  - Regular inbreeding by sib-mating is one of the most successful ecological
      strategies in the bark beetle family Scolytinae. Within this family, the many
      species (119) in Coccotrypes are found breeding in an exceptional variety of
      untraditional woody tissues different from bark and phloem. Species delineation
      by morphological criteria is extremely difficult, however, as in most other
      inbreeding groups of beetles, perhaps due to the unusual evolutionary dynamics
      characterizing sib-mating organisms. Hence, we here performed a phylogenetic
      analysis using molecular data in conjunction with morphological data to better
      understand morphological and ecological evolution in this sib-mating group. We
      used partial DNA sequences from the nuclear gene EF-alpha and the mitochondrial
      genes 12S and CO1 to elucidate patterns of morphological evolution, haplotype
      variation, and evolutionary pathways in resource use. Sequence variation was high
      among species and far above that expected at the species level (e.g., 19% for CO1
      within Coccotrypes advena). The tendency for exhaustive sequence variation at
      deeper nodes resulted in ambiguous reconstructions of the deepest splits.
      However, all results suggested that species with the broadest diets were
      clustered in a single derived position-another piece of evidence against
      specialization as a derived evolutionary feature.

PMID- 12069550
TI  - A phylogenetic analysis of the Arecoid Line of palms based on plastid DNA
      sequence data.
AB  - A phylogenetic analysis of the Arecoid Line (sensu Moore) of palms was conducted
      using 7 kb of coding and noncoding plastid DNA sequence data. Recovered maximum
      parsimony and maximum-likelihood phylogenies support monophyly for the Arecoid
      Line relative to the rest of the family but paraphyly for subfamily Arecoideae
      and polyphyly for subfamily Ceroxyloideae (sensu Dransfield and Uhl). Tribes
      Cocoeae, Geonomeae, Hyophorbeae, and Iriarteae and subfamily Phytelephantoideae
      were identified as monophyletic as were subfamily Phytelephantoideae + Ravenea
      (tribe Ceroxyleae of Ceroxyloideae), Podococcus (tribe Podococceae of Arecoideae)
      + Pseudophoenix (tribe Cyclospatheae of Ceroxyloideae), Reinhardtia (tribe
      Malortieinae) + tribe Cocoeae (both of Arecoideae), and a clade containing all
      IndoPacific pseudomonomerous genera of tribe Areceae (Arecoideae). A few taxa
      show spurious resolution with noncoding plastid DNA data but noncoding data are
      generally congruent with protein-coding data. Biogeographic interpretation
      suggests a Gondwanan origin for the Arecoid Line with several lineages found on
      more than one fragment of the former supercontinent and primary diversification
      in these groups possibly due to continental breakup vicariance. Three groups
      involving Cocos, Orania, and the IndoPacific clade demonstrate independent
      dispersals into the IndoPacific region from a Gondwanan origin.

PMID- 12069551
TI  - Conservation of a dinucleotide simple sequence repeat locus in sharks.
AB  - Recent studies indicate that the flanking region and repeat motif structure of
      conserved microsatellite loci are useful for phylogenetic inference. Most
      comparative studies of microsatellite loci involve relatively closely related
      species, however, primarily because primers developed for one species often
      amplify only related species. We describe an analysis of a microsatellite locus
      in lamniform sharks that we estimate has been conserved for a billion years.
      Combined analysis of the flanking sequence and repeat motif structure resulted in
      a gene tree comparable to those reported from similar analyses of other genes.
      The conservation of the simple sequence repeat (SSR), and of the sequence
      flanking the SSR, is explained by a low substitution rate in sharks coupled with
      the possibility that mutations which interrupt perfect repeats are lost by
      replication slippage.

PMID- 12069552
TI  - Structure, molecular evolution, and phylogenetic utility of the 5(') region of
      the external transcribed spacer of 18S-26S rDNA in Lessingia (Compositae,
      Astereae).
AB  - The 18S-26S nuclear rDNA external transcribed spacer (ETS) has recently gained
      attention as a region that is valuable in phylogenetic analyses of angiosperms
      primarily because it can supplement nucleotide variation from the widely used and
      generally shorter internal transcribed spacers (ITS-1 and ITS-2) and thereby
      improve phylogenetic resolution and clade support in rDNA trees. Subrepeated ETS
      sequences (often occurring in the 5(') region) can, however, create a challenge
      for systematists interested in using ETS sequence data for phylogeny
      reconstruction. We sequenced the 5(')ETS for members of Lessingia (Compositae,
      Astereae) and close relatives (26 taxa total) to characterize the subrepeat
      variation across a group of closely related plant lineages and to gain improved
      understanding of the structure, molecular evolution, and phylogenetic utility of
      the region. The 5(')ETS region of Lessingia and relatives varied in length from
      approximately 245 to 1009 bp due to the presence of a variable number of
      subrepeats (one to eight). We assessed homology of the subrepeats using
      phylogenetic analysis and concluded that only two of the subrepeats and a portion
      of a third ( approximately 282 bp in total) were orthologous across Lessingia and
      could be aligned with confidence and included in further analyses. When the
      partial 5(')ETS data were combined with 3(')ETS and ITS data in phylogenetic
      analyses, no additional resolution of relationships among taxa was obtained
      beyond that found from analysis of 3(')ETS + ITS sequences. Inferred patterns of
      concerted evolution indicate that homogenization is occurring at a faster rate in
      the 3(')ETS and ITS regions than in the 5(')ETS region. Additionally,
      homogenization appears to be acting within but not among subrepeats of the same
      rDNA array. We conclude that challenges in assessing subrepeat orthology across
      taxa greatly limit the utility of the 5(')ETS region for phylogenetic analyses
      among species of Lessingia.

PMID- 12069553
TI  - Molecular phylogenetic analysis of Fringillidae, "New World nine-primaried
      oscines" (Aves: Passeriformes).
AB  - Systematic studies of Fringillidae have long been problematic due to their
      apparent recent and explosive diversification. We present phylogenetic hypotheses
      of 44 fringillids that represent the overall diversity of the family, based on
      3.2 kb of mitochondrial DNA sequences, and phylogenetic analyses for a subset of
      fringillids based on new and published mitochondrial cytochrome b sequences.
      Monophyly of Fringillidae and its two constituent subfamilies, Fringillinae and
      Emberizinae, was consistently supported with the exceptions of Peucedramus being
      placed outside of Fringillinae and Euphonia being placed within Fringillinae
      instead of within Emberizinae. Within Emberizinae, Thraupini (tanagers),
      Cardinalini (cardinals and grosbeaks), and Emberizini (New World sparrows) did
      not form separate monophyletic groups. Our results indicate that Emberizinae
      consists of three clades, each with a different overall geographical
      distribution. Several taxa traditionally considered members of Thraupini fall
      outside of the thraupine clade, including the only North American genus, Piranga.
      Consequently, the thraupine clade includes only Neotropical species. Increasing
      evidence suggests that Fringillidae, often called "New World nine-primaried
      oscines," does not in fact have a New World origin.

PMID- 12069554
TI  - Relationships and evolution of the North African geckos, Geckonia and Tarentola
      (Reptilia: Gekkonidae), based on mitochondrial and nuclear DNA sequences.
AB  - Mitochondrial (cytochrome b and 12S rRNA) and nuclear (c-mos) genes, analyzed by
      a variety of methods, indicate that the distinctive northwest African gecko
      Geckonia chazaliae is a member of the Tarentola clade, being most closely related
      to the species of the western Canary and Cape Verde islands. Relationships in
      Tarentola as a whole are as follows: (T. americana ((T. mauritanica, T.
      angustimentalis) ((T. deserti, T. boehmei) ((T. b. boettgeri-South (T. b.
      boettgeri-North (T. b. bischoffi, T. b. hierrensis))) ((T. annularis, T.
      ephippiata) (Geckonia, T. delalandii, T. gomerensis, Cape Verde species))))));
      nearly all nodes have high bootstrap support. Results confirm that T. americana
      of Cuba and the Bahamas separated at the most basal dichotomy of the phylogeny
      and give no positive support for the monophyly of the subgenera Tarentola s. str.
      and Makariogecko. The latter includes Geckonia and the subgenus Sahelogecko.
      Continental Tarentola appear to have invaded the Sahara desert from its northern
      edge. They have also colonized groups of Atlantic islands five times: a single
      invasion of the West Indies and three of the Canary islands, one of which then
      went on to invade the Cape Verde archipelago. The phylogeny corroborates
      anatomical evidence that the ground-dwelling Geckonia had a climbing ancestry,
      something that is paralleled in some southern African terrestrial gekkonids
      related to Pachydactylus. Distinctive derived features of Geckonia occur in other
      gekkonids that are ground dwelling in arid habitats and may be functionally
      related to this environment. The evolution of such features indicates that,
      although Tarentola is generally very uniform and may have been so for over 10
      million years, this is not due to any overwhelming phylogenetic constraint. G.
      chazaliae should be included in Tarentola, as Tarentola chazaliae.

PMID- 12069555
TI  - Phylogenetics and evolution of the eastern Asian-eastern North American disjunct
      aphid tribe, Hormaphidini (Hemiptera: Aphididae).
AB  - A conspicuous biogeographic pattern of the Northern Hemisphere is the disjunct
      occurrence of related taxa on different continents. Perhaps best studied in
      plants, this pattern includes disjunct distributions of genera in eastern Asia
      and eastern North America. Such continental disjunctions are thought to be the
      remnants of a mostly continuously distributed, mixed mesophytic forest dating to
      the Miocene, which subsequently became fragmented by geological and climatic
      changes. Some highly host-specific insects, namely aphids, live on descendants of
      the mixed mesophytic forest taxa and exhibit the same disjunct distributions as
      that of their host plants. We estimated the phylogeny of Hormaphidini aphids,
      which host-alternate between witch-hazel (Hamamelis; an eastern Asian-eastern
      North American disjunct genus) and birch (Betula). Based on partial nuclear
      elongation factor 1alpha and mitochondrial tRNA leucine/cytochrome oxidase II
      sequences, trees inferred from maximum-parsimony and maximum-likelihood showed
      strong support for two monophyletic genera (Hamamelistes and Hormaphis), each
      containing a clade of Japanese and a clade of North American species. The
      estimated divergence dates of Asian and North American clades in both genera was
      20-30 million years ago, consistent with the idea that aphids may have
      experienced the same vicariance events as those of their host plants.

PMID- 12069556
TI  - A study of the phylogeny of Brassica rapa, B. nigra, Raphanus sativus, and their
      related genera using noncoding regions of chloroplast DNA.
AB  - There are two evolutionary lineages in the genus Brassica: the rapa/oleracea
      lineage and the nigra lineage. Using nuclear DNA sequences such as the intergenic
      spacer between 5S rRNA genes and the internal transcribed spacer between 18S and
      25S rRNA genes, we and others had previously demonstrated that Raphanus sativus
      is closely related to the nigra lineage. In the present study, we sequenced the
      chloroplast noncoding region between trnT and trnF and that between trnD and trnT
      in seven species and showed that R. sativus is more closely related to the
      rapa/oleracea lineage than to the nigra lineage. The conflicting results from
      nuclear DNA and chloroplast DNA support the hypothesis that Raphanus was derived
      from a hybridization between the rapa/oleracea and the nigra lineages. We
      estimated the date of this hybridization event to be 60% of the divergence time
      between the two Brassica lineages. In addition, the pattern and rate of
      nucleotide substitution were studied. There were more transversions than
      transitions in these noncoding regions, which have a high AT content.
      Furthermore, the proportion of transversions among the substitutions at a site
      increases with increasing A + T content of its two adjacent nucleotides. An
      influence of immediate 5(') pyrimidine on substitution pattern is also observed
      when both adjacent bases in the two DNA strands are A or T. The rate of
      nucleotide substitution in the trnL group I intron is only about one third of the
      rate in the nearby intergenic spacers in the trnT-trnF fragment. The rate of
      nucleotide substitution in the rapa/oleracea lineage is at least 1.5 times that
      in the nigra lineage.

PMID- 12069557
TI  - Molecular phylogeny of the Eichhorni group of Delias Hubner, 1819 (Lepidoptera:
      Pieridae).
AB  - The eichhorni group lies within the genus Delias (Lepidoptera: Pieridae) which
      has markedly diversified aposematic wing markings. The phylogenetic relationships
      among all species of the eichhorni group, representatives of each of the other 21
      species groups of Delias butterflies, and some related genera were analyzed based
      on nucleotide sequences of the mitochondrial NADH dehydrogenase subunit 5 gene. A
      supplemental study using the nuclear elongation factor-1alpha (EF-1alpha) gene
      was also carried out. The results are compared with those of morphological
      studies. Our results confirm the monophyly of the eichhorni group and suggest the
      monophyly of the genus Delias. They also indicate phylogenetic intragroup
      relationships, particularly the division of the eichhorni complex into groups I
      and II. Moreover, they also indicate that the initial diversification of the
      eichhorni group involved separation of the D. catisa + D. toxopei clade, followed
      by the divergence of other species including the eichhorni complex. Based on
      these findings, it is supposed that this group first appeared close to or within
      the western mountain range of New Guinea Island (135 degrees 30(')-140 degrees E)
      where D. catisa, D. toxopei, and representatives of other species cohabit.

PMID- 12069558
TI  - Phylogenetic analysis based on 18S ribosomal RNA gene sequences supports the
      existence of class polyacanthocephala (acanthocephala).
AB  - Members of phylum Acanthocephala are parasites of vertebrates and arthropods and
      are distributed worldwide. The phylum has traditionally been divided into three
      classes, Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala; a fourth
      class, Polyacanthocephala, has been recently proposed. However, erection of this
      new class, based on morphological characters, has been controversial. We
      sequenced the near complete 18S rRNA gene of Polyacanthorhynchus caballeroi
      (Polyacanthocephala) and Rhadinorhynchus sp. (Palaeacanthocephala); these
      sequences were aligned with another 21 sequences of acanthocephalans representing
      the three widely recognized classes of the phylum and with 16 sequences from
      outgroup taxa. Phylogenetic relationships inferred by maximum-likelihood and
      maximum-parsimony analyses showed Archiacanthocephala as the most basal group
      within the phylum, whereas classes Polyacanthocephala + Eoacanthocephala formed a
      monophyletic clade, with Palaeacanthocephala as its sister group. These results
      are consistent with the view of Polyacanthocephala representing an independent
      class within Acanthocephala.

PMID- 12069559
TI  - The natural history of the development of obesity in a cohort of young U.S.
      adults between 1981 and 1998.
AB  - BACKGROUND: Understanding the natural history of obesity in a population may be a
      critical step toward developing effective interventions. OBJECTIVE: To assess the
      development of body mass and examine the role of race or ethnicity, sex, and
      birth year in obesity onset in young U.S. adults. DESIGN: Prospective cohort
      study. SETTING: The National Longitudinal Survey of Youth 1979, a national sample
      with oversampling of minority ethnic groups. PARTICIPANTS: 9179 persons.
      MEASUREMENTS: Body mass index (BMI) calculated from 12 self-reported height and
      weight samples recorded between 1981 and 1998. Logistic regression identified
      predictors of obesity at age 35 to 37 years. Cox proportional hazards models
      compared the incidence of obesity by ethnicity and birth year. RESULTS: Overall,
      26% of men and 28% of women were obese (BMI > or = 30 kg/m2) by age 35 to 37
      years. Race or ethnicity and baseline BMI were significant predictors of obesity.
      Obesity onset was 2.1 (95% CI, 1.6 to 2.7) times faster for black women and 1.5
      (CI, 1.1 to 2.0) times faster for Hispanic women than for white women. The
      pattern for men differed: Overall, obesity developed most rapidly in Hispanic
      men, but relative rates of obesity onset for white men compared with black men
      varied according to age. The rate of obesity onset increased 26% to 28% over an 8
      year span in birth year. CONCLUSIONS: Marked ethnic-based differences were found
      in rates of weight accumulation in young U.S. adults, with later birth cohorts
      experiencing earlier onset of obesity. To alter the course of obesity in the
      United States, interventions should target young adults, especially those of
      minority ethnic groups.

PMID- 12069560
TI  - Prospective study of color duplex ultrasonography compared with contrast
      venography in patients suspected of having deep venous thrombosis of the upper
      extremities.
AB  - BACKGROUND: The optimal strategy for diagnosis of deep venous thrombosis (DVT) is
      less well established for the upper extremities than for the lower extremities.
      Duplex color ultrasonography can be difficult to perform in the upper extremities
      because of their anatomy, and contrast venography is often indicated. Moreover,
      limited data exist on the use of duplex color ultrasonography in this setting.
      OBJECTIVE: To determine the accuracy of duplex ultrasonography for diagnosis of
      DVT of the upper extremities. DESIGN: Prospective study of duplex ultrasonography
      compared with venography. SETTING: A teaching hospital in Amsterdam, the
      Netherlands. PATIENTS: 126 consecutive inpatients and outpatients with suspected
      DVT of the upper extremities. MEASUREMENTS: Contrast venography was obtained
      after duplex ultrasonography and was judged independently. A three-step protocol,
      involving compression ultrasonography, color ultrasonography, and color Doppler
      ultrasonography, was used. Sensitivity, specificity, and likelihood ratios for
      ultrasonography as a whole were calculated. The independent value of each step
      was assessed. RESULTS: Venography and ultrasonography were not feasible in 23 of
      126 patients (18%) and 1 of 126 patients (0.8%), respectively. Results of
      ultrasonography were inconclusive in 3 patients. Venography demonstrated
      thrombosis in 44 of 99 patients (44%); in 36 patients (36%), thrombosis was
      related to intravenous catheters or malignant disease. Sensitivity and
      specificity of duplex ultrasonography were 82% (95% CI, 70% to 93%) and 82% (CI,
      72% to 92%), respectively. Venous incompressibility correlated well with
      thrombosis, whereas only 50% of isolated flow abnormalities proved to be
      thrombosis-related. CONCLUSIONS: Duplex ultrasonography may be the method of
      choice for initial diagnosis of patients with suspected thrombosis of the upper
      extremities. However, in patients with isolated flow abnormalities, contrast
      venography should be performed.

PMID- 12069561
TI  - The ankle brachial index is associated with leg function and physical activity:
      the Walking and Leg Circulation Study.
AB  - BACKGROUND: The ankle brachial index (ABI) is a noninvasive, reliable measure of
      lower-extremity ischemia. However, the relationship between ABI and lower
      extremity function has not been well studied. OBJECTIVE: To describe the
      association between the ABI and lower-extremity function. DESIGN: Cross-sectional
      study. SETTING: 3 academic medical centers in the Chicago area. PARTICIPANTS: 740
      men and women (460 with peripheral arterial disease). MEASUREMENTS: Accelerometer
      measured physical activity over 7 days, 6-minute walk, 4-m walking velocity,
      standing balance, and ABI. RESULTS: 33% of participants with peripheral arterial
      disease had intermittent claudication. Fewer than 40% of participants with an ABI
      less than 0.40 walked continuously for 6 minutes compared with more than 95% of
      participants with an ABI between 1.00 and 1.50. Compared with an ABI of 1.10 to
      1.50, an ABI less than 0.50 was associated with shorter distance walked in 6
      minutes (beta-regression coefficient = -523 ft [95% CI, -592 to -454 ft]; P <
      0.001), less physical activity (beta = -514.8 activity units [CI, -657 to -373
      activity units]; P < 0.001), slower 4-m walking velocity (beta = -0.21 m/s [CI, 
      0.27 to -0.15 m/s]; P < 0.001), and less likelihood of maintaining a tandem stand
      for 10 seconds (odds ratio, 0.37 [CI, 0.18 to 0.76]; P = 0.007), after adjustment
      for typical confounders. Associations between ABI and function were stronger than
      associations between leg symptoms and function. CONCLUSIONS: The ABI, a
      noninvasive test that can be performed in a medical office, is more closely
      associated with leg function in persons with peripheral arterial disease than is
      intermittent claudication or other leg symptoms. These data support the use of
      the ABI to identify abnormal lower-extremity function.

PMID- 12069562
TI  - Enteric pathogens in Mexican sauces of popular restaurants in Guadalajara,
      Mexico, and Houston, Texas.
AB  - BACKGROUND: The transmission of traveler's diarrhea is primarily foodborne.
      OBJECTIVE: To examine the level of microbial contamination of tabletop sauces
      found in Mexican-style restaurants. DESIGN: Cross-sectional study of Mexican
      sauces. SETTING: Mexican restaurants in Guadalajara, Mexico, and Houston, Texas,
      during the summer of 1998. MEASUREMENTS: 71 sauces from Guadalajara and 25 sauces
      from Houston were examined. The number of sauces contaminated with Escherichia
      coli, the median number of E. coli colonies per gram of sauce, and
      enteropathogens were identified. RESULTS: 47 of 71 sauces from Guadalajara were
      contaminated with E. coli versus 10 of 25 sauces from Houston (P = 0.03); the
      median number of E. coli colonies per gram of sauce was 1000 in the Guadalajara
      sauces versus 0.0 in the Houston sauces (P = 0.007). Among sauces from
      Guadalajara tested for diarrheogenic E. coli, 4 of 43 sauces contained
      enterotoxigenic E. coli and 14 of 32 contained enteroaggregative E. coli.
      CONCLUSIONS: Contamination with E. coli was common in samples of Mexican tabletop
      sauces from Guadalajara restaurants. These sauces commonly contained enteric
      pathogens.

PMID- 12069563
TI  - Truth survival in clinical research: an evidence-based requiem?
AB  - PURPOSE: Factors associated with the survival of truth of clinical conclusions in
      the medical literature are unknown. The authors hypothesized that conclusions
      derived from studies using better methodology should have a longer half-life.
      DATA SOURCES: MEDLINE and hand searches of journals with studies on cirrhosis and
      hepatitis. STUDY SELECTION: Original articles and meta-analyses published from
      1945 to 1999 about cirrhosis or hepatitis in adults. DATA SYNTHESIS: In 2000, 285
      of 474 conclusions (60%) were still considered to be true, 91 (19%) were
      considered to be obsolete, and 98 (21%) were considered to be false. The half
      life of truth was 45 years. The 20-year survival of conclusions derived from meta
      analysis was lower (57% +/- 10%) than that from nonrandomized studies (87% +/-
      2%) (P < 0.001) or randomized trials (85% +/- 3%) (P < 0.001). The survival of
      conclusions was not different when studies of high methodologic quality were
      compared with those of low quality. In randomized trials, the 50-year survival
      rate was higher for 52 negative conclusions (68% +/- 13%) than for 118 positive
      conclusions (14% +/- 4%) (P < 0.001). CONCLUSIONS: Contrary to the authors'
      hypothesis, conclusions based on recognized, good methodology had no clear
      survival advantage. To better convince clinicians of the long-term utility of
      evidence-based medicine, better prognostic factors should be developed.

PMID- 12069564
TI  - Update on spondyloarthropathies.
AB  - Spondyloarthropathies are a cluster of interrelated and overlapping chronic
      inflammatory rheumatic diseases that primarily include ankylosing spondylitis,
      reactive arthritis, and the arthritis associated with psoriasis and inflammatory
      bowel diseases. The primary pathologic sites are the entheses (the sites of bony
      insertion of ligaments and tendons); the axial skeleton, including the sacroiliac
      joints; the limb joints; and some nonarticular structures, such as the gut, skin,
      eye, and aortic valve. Although spondyloarthropathies are not associated with
      rheumatoid factor, they show a strong association with HLA-B27; however, this
      association varies markedly among various spondyloarthropathies and among ethnic
      groups. The most widely used classification criterion, from the European
      Spondyloarthropathy Study Group, encompasses the currently recognized wider
      disease spectrum, with a sensitivity and specificity that generally exceed 85%.
      Spondyloarthropathies occur in genetically predisposed persons and are triggered
      by environmental factors, but the cellular and molecular mechanisms of
      inflammation are not yet fully understood. Chlamydial and many enterobacterial
      infections can trigger reactive arthritis, but an infectious trigger for
      ankylosing spondylitis has not yet been established. HLA-B27 itself is involved
      in enhancing genetic susceptibility, but the underlying molecular basis is still
      unknown; additional genes include the putative susceptibility genes for Crohn
      disease, ulcerative colitis, and psoriasis. A specific susceptibility gene for
      Crohn disease, NOD2, is located on chromosome 16q12, and one of the candidate
      genes for psoriasis, PSORS1, has been mapped to a 60-kb fragment on chromosome
      6p, which is telomeric to the HLA-C locus. This paper reviews the efficacy of
      anti-tumor necrosis factor-alpha therapy and other therapeutic advances.

PMID- 12069566
TI  - Understanding the complex journey to obesity in early adulthood.

PMID- 12069565
TI  - Rheumatoid arthritis--a molecular understanding.
AB  - The application of molecular immunology techniques in the study of rheumatoid
      arthritis has resulted in an explosion of knowledge on the risk factors for the
      disease, predictors of disease severity, the molecular mechanisms of inflammatory
      responses, and mechanisms of tissue destruction. We know, for example, that
      inheriting certain genes in the major histocompatibility complex partly dictates
      susceptibility and severity of rheumatoid arthritis. These genes and others in
      the major histocompatibility complex are critical for the occurrence of immune
      responses both constructive (prevention of infection, surveillance for malignant
      cells) and destructive (development of autoimmune diseases). We also now
      understand mechanisms of cell communication, regulation of immune responses, how
      the cells that mediate immune responses and tissue injury accumulate in tissues,
      and how the injury occurs. The knowledge itself is satisfying, but more
      important, based on this knowledge, effective and reasonably safe treatments that
      address basic mechanisms of the disease process have been developed and are now
      widely used. In fact, the newer treatments represent the "tip of the iceberg,"
      and as our basic knowledge increases, so too will the armamentarium with which we
      can fight rheumatoid arthritis and other similar autoimmune diseases.

PMID- 12069567
TI  - The CONSORT statement: explanation and elaboration. Consolidated Standards of
      Reporting Trials.

PMID- 12069568
TI  - The CONSORT statement: explanation and elaboration. Consolidated Standards of
      Reporting Trials.

PMID- 12069570
TI  - Summaries for patients. The development of obesity in young U.S. adults, 1981
      1998.

PMID- 12069571
TI  - Summaries for patients. Duplex ultrasonography for diagnosis of blood clots in
      the arms and shoulders.

PMID- 12069572
TI  - Summaries for patients. Associations between peripheral arterial disease and leg
      function.

PMID- 12069573
TI  - Summaries for patients. Bacteria in condiment sauces on tables in Mexican-style
      restaurants in Guadalajara, Mexico, and Houston, Texas.

PMID- 12069575
TI  - Multiple Q-cycle bypass reactions at the Qo site of the cytochrome bc1 complex.
AB  - The cytochrome (cyt) bc(1) complex is central to energy transduction in many
      species. Most investigators now accept a modified Q-cycle as the catalytic
      mechanism of this enzyme. Several thermodynamically favorable side reactions must
      be minimized for efficient functioning of the Q-cycle. Among these, reduction of
      oxygen by the Q(o) site semiquinone to produce superoxide is of special
      pathobiological interest. These superoxide-producing bypass reactions are most
      notably observed as the antimycin A- or myxothiazol-resistant reduction of cyt c.
      In this work, we demonstrate that these inhibitor-resistant cyt c reductase
      activities are largely unaffected by removal of O(2) in the isolated yeast cyt
      bc(1) complex. Further, increasing O(2) tension 5-fold stimulated the antimycin A
      resistant reduction by a small amount ( approximately 25%), while leaving the
      myxothiazol-resistant reduction unchanged. This most likely indicates that the
      rate-limiting step in superoxide production is the formation of a reactive
      species (probably a semiquinone), capable of rapid O(2) reduction, and that in
      the absence of O(2) this species can reduce cyt c by some other pathway. We
      suggest as one possibility that a semiquinone escapes from the Q(o) site and
      reduces either O(2) or cyt c directly. The small increase in antimycin A
      resistant cyt c reduction rate at high O(2) can be explained by the accumulation
      of a low concentration of a semiquinone inside the Q(o) site. Under aerobic
      conditions, addition of saturating levels of superoxide dismutase (SOD) inhibited
      50% of cyt c reduction in the presence of myxothiazol, implying that essentially
      all bypass reactions occur with the production of superoxide. However, SOD
      inhibited only 35% of antimycin A-resistant cyt c reduction, suggesting the
      presence of a second, slower bypass reaction that does not reduce O(2). Given
      that myxothiazol blocks cyt b reduction whereas antimycin A promotes it, we
      propose that this second bypass occurs by reduction of the Q(o) site semiquinone
      by prereduced cyt b(L).

PMID- 12069574
TI  - Stoichiometries of protein-protein/DNA binding and conformational changes for the
      transition-state regulator AbrB measured by pseudo cell-size exclusion
      chromatography-mass spectrometry.
AB  - We have developed on-line pseudo cell-size exclusion chromatography-mass
      spectrometry (PsC-SEC-MS) for the rapid, real time analyses of noncovalently
      bound protein complexes. The methodology can be used to determine constituent
      components of such complexes, as well as exact stoichiometries. Furthermore, it
      enables the efficient determination of gross conformational changes upon
      complexation. The power of the new approach is demonstrated in the analysis of
      the global transition-state regulator AbrB and its complex with a target DNA
      sequence from the promoter sinIR. Using PsC-SEC-MS, we confirm that AbrB is
      assembled as a homotetramer and not as a homohexamer as previously suggested.
      Additionally, we show that AbrB binds to the sinIR DNA target element as a
      homotetramer, affording a 4:1 protein:DNA stoichiometry. Finally, we demonstrate
      that when the complex binds to sinIR, the hydrodynamic volume (size) of the
      complex is notably reduced compared to that of the apoprotein, indicating a
      protein conformational change.

PMID- 12069576
TI  - Light-induced changes in the structure and accessibility of the cytoplasmic loops
      of rhodopsin in the activated MII state.
AB  - Bovine rhodopsin was specifically labeled on the cytoplasmic surface at cysteine
      140 (the first residue of the loop connecting helices III and IV) or at cysteine
      316 (in the loop connecting helix VII and the palmitoylation sites) with the
      fluorescent labels fluorescein and Texas Red. These loops are involved in
      activation and signal transduction. The time-resolved fluorescence depolarization
      was measured in the dark state and in the M(II) state, with labeled samples
      consisting of rhodopsin-octylglucoside micelles or rod outer segment (ROS)
      membranes. In this way the diffusional dynamics of the flexible loops of
      rhodopsin were measured for the first time directly on the nanosecond time scale.
      Control experiments showed that the large number of weak excitation pulses
      required in these single photon counting experiments leads to <5% bleaching of
      the sample. Rhodopsin was trapped in the activated M(II) state for the duration
      of the fluorescence experiments ( approximately 20 min) after illumination at pH
      6 and 5 degrees C. For both types of samples and at both labeled positions the
      dynamics of the label and loop motion as monitored by the time constants of the
      depolarization were not significantly different in the two states of the
      receptor. The end-anisotropy increased, however, from 0.09 in the dark to 0.16 in
      the M(II) state for ROS samples labeled at C140. The corresponding numbers for
      the C316 position are 0.06 and 0.12. Light-induced activation in M(II) is thus
      associated with a large increase in the loop steric hindrance due to a changed
      loop domain structure on the cytoplasmic surface. These results are supported by
      fluorescence quenching experiments with I(-), which indicate a significant
      decrease in the collisional quenching constant k(q) and in accessibility in the
      M(II) state at both positions. The rotational correlation time of the rhodopsin
      micelles increased from 48 ns in the dark state to 60 ns in M(II). This increase
      is caused by a change in volume and/or shape and is consistent with a structural
      change. These results demonstrate that time-resolved fluorescence depolarization
      is a powerful tool to study the changes in conformation and dynamics of the
      cytoplasmic loops that accompany the activation of rhodopsin and other G-protein
      coupled receptors.

PMID- 12069577
TI  - Selective uptake from LDL is stimulated by unsaturated fatty acids and modulated
      by cholesterol content in the plasma membrane: role of plasma membrane
      composition in regulating non-SR-BI-mediated selective lipid transfer.
AB  - We previously reported that unsaturated fatty acids stimulated low-density
      lipoprotein (LDL) particle uptake in J774 macrophages by increasing LDL receptor
      activity. Since free fatty acids (FFA) also change plasma membrane properties, a
      putative cholesteryl ester (CE) acceptor for selective uptake (SU), we questioned
      the ability of FFA to modulate SU from LDL. Using [(3)H]cholesteryl ether/(125)I
      LDL to trace CE core and whole particle uptake, we found that oleic acid and
      eicosapentaenoic acid, but not saturated stearic acid, increased SU by 30% over
      control levels. An ACAT inhibitor, Dup128, abolished FFA effects on SU,
      indicating that increased SU by FFA was secondary to changes in cell-free
      cholesterol (FC). Consistent with these observations, ACAT inhibition increased
      cell FC and reduced LDL SU by half. The important role of plasma membrane
      composition was further demonstrated in that beta-cyclodextrin- (beta-CD-)
      mediated FC removal from the plasma membrane increased SU from LDL and was
      further stimulated by U18666A, a compound that inhibits FC transport between
      lysosomes and the plasma membrane. In contrast, cholesterol-saturated beta-CD
      markedly reduced LDL SU. In contrast to LDL SU, oleic acid, ACAT inhibition,
      U18666A, or beta-CD had no effects on HDL SU. Moreover, HDL SU was inhibited by
      antimouse SR-BI antibody by more than 50% but had little effect on LDL SU. In
      C57BL/6 mice fed a high fat diet, plasma FFA levels increased, and SU accounted
      for an almost 4-fold increased proportion of total cholesterol delivery to the
      arterial wall. Taken together, these data suggest that LDL SU is mediated by
      pathways independent of SR-BI and is influenced by plasma membrane FC content.
      Moreover, in conditions where elevated plasma FFA occur, SU from LDL can be an
      important mechanism for cholesterol delivery in vivo.

PMID- 12069578
TI  - Residues in the epsilon subunit of the nicotinic acetylcholine receptor interact
      to confer selectivity of waglerin-1 for the alpha-epsilon subunit interface site.
AB  - Waglerin-1 (Wtx-1) is a 22-amino acid peptide that competitively antagonizes
      muscle nicotinic acetylcholine receptors (nAChRs). Previous work demonstrated
      that Wtx-1 binds to mouse nAChRs with higher affinity than receptors from rats or
      humans, and distinguished residues in alpha and epsilon subunits that govern the
      species selectivity. These studies also showed that Wtx-1 binds selectively to
      the alpha-epsilon binding site with significantly higher affinity than to the
      alpha-delta binding site. Here we identify residues at equivalent positions in
      the epsilon, gamma, and delta subunits that govern Wtx-1 selectivity for one of
      the two binding sites on the nAChR pentamer. Using a series of chimeric and point
      mutant subunits, we show that residues Gly-57, Asp-59, Tyr-111, Tyr-115, and Asp
      173 of the epsilon subunit account predominantly for the 3700-fold higher
      affinity of the alpha-epsilon site relative to that of the alpha-gamma site.
      Similarly, we find that residues Lys-34, Gly-57, Asp-59, and Asp-173 account
      predominantly for the high affinity of the alpha-epsilon site relative to that of
      the alpha-delta site. Analysis of combinations of point mutations reveals that
      Asp-173 in the epsilon subunit is required together with the remaining
      determinants in the epsilon subunit to achieve Wtx-1 selectivity. In particular,
      Lys-34 interacts with Asp-173 to confer high affinity, resulting in a
      DeltaDeltaG(INT) of -2.3 kcal/mol in the epsilon subunit and a DeltaDeltaG(INT)
      of -1.3 kcal/mol in the delta subunit. Asp-173 is part of a nonhomologous
      insertion not found in the acetylcholine binding protein structure. The key role
      of this insertion in Wtx-1 selectivity indicates that it is proximal to the
      ligand binding site. We use the binding and interaction energies for Wtx-1 to
      generate structural models of the alpha-epsilon, alpha-gamma, and alpha-delta
      binding sites containing the nonhomologous insertion.

PMID- 12069579
TI  - Interaction of fibrin(ogen) with fibronectin: further characterization and
      localization of the fibronectin-binding site.
AB  - The interaction of fibronectin with fibrin and its incorporation into fibrin
      clots are thought to be important for the formation of a provisional matrix that
      promotes cell adhesion and migration during wound healing. However, it is still
      unclear whether fibronectin interacts with both fibrin and fibrinogen or fibrin
      only and whether fibronectin binds exclusively to the fibrin(ogen) alphaC
      domains. To address these questions, we studied the interaction of fibronectin
      with fibrinogen, fibrin, and their proteolytic and recombinant fragments. In both
      ELISA and surface plasmon resonance (SPR) experiments, immobilized fibrinogen did
      not bind fibronectin at all, but after conversion to fibrin, it bound fibronectin
      with high affinity. To test which regions of fibrin are involved in this binding,
      we studied the interaction of fibronectin with the fibrin-derived D-D:E(1)
      complex and a recombinant alphaC fragment (residues Aalpha221-610) corresponding
      to the alphaC domain that together encompass the whole fibrin(ogen) molecule. In
      ELISA, when fibronectin was added to the immobilized D-D:E(1) complex or the
      immobilized alphaC fragment, only the latter exhibited binding. Likewise, when
      fibronectin was immobilized and the complex or the alphaC fragment was added,
      only the latter was observed to bind. The selective interaction between
      fibronectin and the alphaC fragment was confirmed by SPR. The fibronectin-binding
      site was further localized to the NH(2) terminal connector region of the alphaC
      domain since in ELISA, the immobilized recombinant Aalpha221-391 sub-fragment
      bound fibronectin well while the immobilized recombinant Aalpha392-610 sub
      fragment exhibited no binding. This finding was confirmed by ligand blotting
      analysis. Thus, the results provide direct evidence for the existence of a
      cryptic high-affinity fibronectin-binding site in the Aalpha221-391 region of the
      fibrinogen alphaC domain that is not accessible in fibrinogen but becomes exposed
      in fibrin.

PMID- 12069580
TI  - Molecular cloning and developmental expression of the caveolin gene family in the
      amphibian Xenopus laevis.
AB  - Caveolae are approximately 50-100 nm invaginations of the plasma membrane thought
      to form as a result of a local accumulation of cholesterol, sphingolipids, and a
      unique family of three proteins known as the caveolins: Cav-1, -2, and -3. Here,
      we report the identification, sequence, and developmental expression of the three
      caveolin genes in the amphibian Xenopus laevis. Sequence comparisons show that
      Xenopus Cav-1, -2, and -3 are approximately 80, 64, and 45% identical,
      respectively, to their counterparts in humans. Furthermore, Northern blotting
      experiments demonstrate that the Xenopus caveolins have tissue-specific
      expression profiles consistent with those previously reported in adult mammals.
      In the adult frog, Xenopus Cav-1 and Cav-2 are most abundantly expressed in the
      fat body and the lungs, while Xenopus Cav-3 is primarily expressed in muscle
      tissue types (heart and skeletal muscle). However, our temporal and spatial
      analyses of these expression patterns during embryogenesis reveal several novel
      features, with possible relevance to developmental signaling. Transcripts
      encoding Xenopus Cav-1 and -2 first appear in the notochord of neurula stage
      embryos, which represents a key signaling tissue. In contrast, Xenopus Cav-3
      shows a highly specific punctate expression pattern in the embryonic epidermis,
      similar to previous patterns implicated in Notch signaling. These findings are in
      striking contrast to their steady-state expression patterns in the adult frog.
      Taken together, our results show that the Xenopus caveolin gene family is present
      and differentially expressed in both embryonic and adult tissues. This report is
      the first detailed study of caveolin gene expression in a developing embryo.

PMID- 12069581
TI  - Translocation of branched-chain arginine peptides through cell membranes:
      flexibility in the spatial disposition of positive charges in membrane-permeable
      peptides.
AB  - A basic peptide derived from HIV-1 Tat has been reported to have the ability to
      translocate through cell membranes and to bring exogenous proteins into cells. We
      have demonstrated that these features could be observed among many arginine-rich
      peptides, and the presence of a ubiquitous internalization mechanism for arginine
      rich oligopeptides has been suggested. In this report, we report that these
      features are also applicable to the peptides having branched-chain structures.
      Peptides that have arginine residues on four branched chains (R(n))(4) [n (number
      of arginine residues)= 0-6] were prepared. Fluorescence microscopic observation
      revealed that the (R(2))(4) peptide exhibited the most efficient translocation.
      The dependence on the number of arginine residues of the translocation efficiency
      and cellular localization was also observed for the branched-chain peptides as
      was seen in the linear peptides. Quite interestingly, efficient translocation was
      also recognized in the (RG(3)R)(4) peptide, where three glycine residues
      intervened between two arginine residues on each chain of (R(2))(4). The results
      strongly suggested that a linear structure was not indispensable for the
      translocation of arginine-rich peptides and that there could be considerable
      flexibility in the location of the arginine residue in the molecules.

PMID- 12069582
TI  - Role of the large cytoplasmic loop of the alpha 7 neuronal nicotinic
      acetylcholine receptor subunit in receptor expression and function.
AB  - The role of the large intracellular loop of the nicotinic acetylcholine receptor
      (nAChR) alpha7 subunit in the expression of functional channels was studied. For
      this purpose, systematic deletions and substitutions were made throughout the
      loop and the ability of the mutated alpha7 subunits to support expression of
      functional nAChRs at the Xenopus oocyte membrane was tested. Surface nAChR
      expression was abolished upon removal of sequences at two regions, a 29-amino
      acid segment close to the N-terminus of the loop (amino acids 297-325) and
      adjacent to the third transmembrane region and an 11-amino acid segment near the
      fourth transmembrane region. Some residues (amino acids 317-322) within the 29
      amino acids N-terminal segment could be substituted by others but not deleted
      without loss of expression, suggesting that a certain structure, determined by
      the number of amino acids rather than by their identity, has to be maintained in
      this region. The contiguous sequence M323 K324 R325 did not tolerate deletions
      and substitutions. Removal of the rest of the cytoplasmic loop was not
      deleterious; even higher expression levels (2-4-fold) were obtained upon large
      deletions of the loop (Delta399-432 and Delta339-370). High expression levels
      were observed provided that a minimal sequence of three amino acids (E371, G372,
      and M373) was present. In addition, some electrophysiological properties of
      mutant nAChRs were modified. Substitution of the EGM sequence by other protein
      segments produced a variety of effects, but, in general, insertions were not well
      tolerated, suggesting the existence of tight structural restrictions in the large
      cytoplasmic region of the rat alpha7 subunit.

PMID- 12069583
TI  - Binding site on human von Willebrand factor of bitiscetin, a snake venom-derived
      platelet aggregation inducer.
AB  - Bitiscetin, a C-type lectin-like heterodimeric snake venom protein purified from
      Bitis arietans, binds to human von Willebrand factor (VWF) and induces the
      platelet membrane glycoprotein (GP) Ib-dependent platelet agglutination in vitro
      similar to botrocetin. In contrast with botrocetin which binds to the A1 domain
      of VWF, the A3 domain, a major collagen-binding site of VWF, was proposed to be a
      bitiscetin-binding site. In the competitive binding assay, neither bitiscetin nor
      botrocetin had an inhibitory effect on the VWF binding to the immobilized type
      III collagen on a plastic plate. The anti-VWF monoclonal antibody NMC-4, which
      inhibits VWF-induced platelet aggregation by binding to alpha4 helix of the A1
      domain, also inhibited bitiscetin binding to the VWF. Binding of VWF to the
      immobilized bitiscetin was competitively inhibited by a high concentration of
      botrocetin. A panel of recombinant VWF, in which alanine-scanning mutagenesis was
      introduced to the charged amino acid residues in the A1 domain, showed that the
      bitiscetin-binding activity was reduced in mutations at Arg632, Lys660, Glu666,
      and Lys673 of the A1 domain. Those substituted at Arg629, Arg636, and Lys667,
      which decreased the botrocetin binding, showed no effect on the bitiscetin
      binding. These results indicate that bitiscetin binds to a distinct site in the
      A1 domain of VWF spanning over alpha4a, alpha5 helices and the loop between
      alpha5 and beta6 but close to the botrocetin- and NMC-4-binding sites. Monoclonal
      antibodies recognizing the alpha-subunit of bitiscetin specifically inhibited
      bitiscetin-induced platelet agglutination without affecting the binding between
      VWF and bitiscetin, suggesting that the alpha-subunit of bitiscetin is located on
      VWF closer to the GPIb-binding site than the beta-subunit is. Bitiscetin and
      botrocetin might modulate VWF by binding to the homologous region of the A1
      domain to induce a conformational change leading to an increased accessibility to
      platelet GPIb.

PMID- 12069584
TI  - Evaluating the roles of thrombin and calcium in the activation of coagulation
      factor XIII using H/D exchange and MALDI-TOF MS.
AB  - Factor XIII catalyzes the formation of isopeptide bonds between noncovalently
      associated fibrin monomers in the final stages of the blood coagulation cascade.
      This results in a rigid, covalently linked network that is much more resistant to
      proteolytic degradation. Calcium ion is critical to this process, and its
      continued presence after activation aids in maintenance of Factor XIII activity.
      Hydrogen/deuterium exchange experiments were conducted on recombinant Factor XIII
      a(2) using matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry. The method revealed changes in the structure of Factor XIII a(2)
      localized to different areas of the protein that were related to the manner in
      which the enzyme was activated and the calcium environment in which it was
      maintained. A possible substrate recognition region in the catalytic core (220
      230) shows an increase in deuteration upon activation. The degree of deuteration
      varies depending on the calcium environment in which the active enzyme is
      maintained. A portion of the beta-sandwich domain (98-104) exhibits a decrease in
      deuteration upon activation by exposure to calcium alone. A third change occurs
      in the beta-barrel 1 domain of the protein, a portion of which (526-546) shows a
      decrease in deuteration upon activation by calcium exposure, but almost none at
      all when the enzyme is activated by thrombin. The pattern of observed changes
      reveals individual contributions of calcium and thrombin to activating the enzyme
      toward substrate binding and exposure of the active site.

PMID- 12069586
TI  - Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 2. X-ray
      absorption studies of native enzyme and anaerobic complexes with the substrates
      quercetin and myricetin.
AB  - Quercetin 2,3-dioxygenase (2,3QD) is a mononuclear copper-dependent dioxygenase
      which catalyzes the cleavage of the heterocyclic ring of the flavonol quercetin
      (5,7,3',4'-tetrahydroxy flavonol) to produce 2-protocatechuoyl-phloroglucinol
      carboxylic acid and carbon monoxide. In this study, X-ray absorption spectroscopy
      has been used to characterize the local structural environment of the Cu(2+)
      center of Aspergillus japonicus 2,3QD. Analysis of the EXAFS region of native
      2,3QD at functionally relevant pH (pH 6.0) indicates an active site equally well
      described by either four or five ligands (3N(His) + 1-2O) at an average distance
      of 2.00 A. Bond valence sum analysis confirms that the best model is somewhere
      between the two. When, however, 2,3QD is anaerobically complexed with its natural
      substrate quercetin, the copper environment undergoes a transition to a five
      coordinated cage, which is also best modeled by a single shell of N/O scatterers
      at the average distance of 2.00 A. This coordination is independently confirmed
      by the anaerobic complex with myricetin (5'-hydroxy quercetin). XANES analysis
      confirms that substrate binding does not reduce the Cu(2+) ion. The present study
      gives the first direct insights into the coordination chemistry of the enzyme
      complexed with its substrates. It suggests that activation for O(2) attack is
      achieved by monodentate substrate complexation to the copper ion through the 3
      hydroxyl group. In addition, monodentate carboxylate ligation by the Glu73 side
      chain is likely to play a role in the fine-tuning of the equilibrium leading to
      the formation of the activated E.S complex.

PMID- 12069585
TI  - Functional analysis of the copper-dependent quercetin 2,3-dioxygenase. 1. Ligand
      induced coordination changes probed by X-ray crystallography: inhibition,
      ordering effect, and mechanistic insights.
AB  - The crystal structures of the copper-dependent Aspergillus japonicus quercetin
      2,3-dioxygenase (2,3QD) complexed with the inhibitors diethyldithiocarbamate
      (DDC) and kojic acid (KOJ) are reported at 1.70 and 2.15 A resolution,
      respectively. Both inhibitors asymmetrically chelate the metal center and assume
      a common orientation in the active site cleft. Their molecular plane blocks
      access to the inner portion of the cavity which is lined by the side chains of
      residues Met51, Thr53, Phe75, Phe114, and Met123 and which is believed to bind
      the flavonol B-ring of the natural substrate. The binding of the inhibitors
      brings order into the mixed coordination observed in the native enzyme. DDC and
      KOJ induce a single conformation of the Glu73 side chain, although in different
      ways. In the presence of DDC, Glu73 is detached from the copper ion with its
      carboxylate moiety pointing away from the active site cavity. In contrast, when
      KOJ is bound, Glu73 ligates the Cu ion through its O(epsilon)(1) atom with a
      monodentate geometry. Compared to the native coordinating conformation, this
      conformation is approximately 90 degrees rotated about the chi(3) angle. This
      latter Glu73 conformation is compatible with the presence of a bound substrate.

PMID- 12069587
TI  - A new electron transport mechanism in mitochondrial steroid hydroxylase systems
      based on structural changes upon the reduction of adrenodoxin.
AB  - The adrenal ferredoxin (adrenodoxin, Adx) is an acidic 14.4-kDa [2Fe-2S]
      ferredoxin that belongs to the vertebrate ferredoxin family. It is involved in
      the electron transfer from the flavoenzyme NADPH-adrenodoxin-reductase to
      cytochromes P-450(scc) and P-450(11)(beta). The interaction between the redox
      partners during electron transport has not yet been fully established.
      Determining the tertiary structure of an electron-transfer protein may be very
      helpful in understanding the transport mechanism. In the present work, we report
      a structural study on the oxidized and reduced forms of bovine adrenodoxin (bAdx)
      in solution using high-resolution NMR spectroscopy. The protein was produced in
      Escherichia coli and singly or doubly labeled with (15)N or (13)C/(15)N,
      respectively. Approximately 70 and 75% of the (15)N, (13)C, and (1)H resonances
      could be assigned for the reduced and the oxidized bAdx, respectively. The
      secondary and tertiary structures of the reduced and oxidized states were
      determined using NOE distance information. (1)H(N)-T(1) relaxation times of
      certain residues were used to obtain additional distance constraints to the [2Fe
      2S] cluster. The results suggest that the solution structure of oxidized Adx is
      quite similar to the X-ray structure. However, structural changes occur upon
      reduction of the [2Fe-2S] cluster, as indicated by NMR measurements. It could be
      shown that these conformational changes, especially in the C-terminal region,
      cause the dissociation of the Adx dimer upon reduction. A new electron transport
      mechanism proceeding via a modified shuttle mechanism, with both monomers and
      dimers acting as electron carriers, is proposed.

PMID- 12069588
TI  - Differential interactions of estrogens and antiestrogens at the 17 beta-hydroxyl
      or counterpart hydroxyl with histidine 524 of the human estrogen receptor alpha.
AB  - We investigated the role of H524 of the human estrogen receptor alpha (ERalpha)
      for the binding of various estrogens [estradiol (E(2)), 3-deoxyestradiol (3
      dE(2)), and 17beta-deoxyestradiol (17beta-dE(2))] and antiestrogens [4
      hydroxytamoxifen (OHT), RU 39 411 (RU), and raloxifene (Ral)], which possess the
      17beta-hydroxyl or counterpart hydroxyl (designated: 17beta/c-OH), with the
      exception of 17beta-dE(2) and OHT. The work involved a comparison of the binding
      affinities of these ligands for wild-type and H524 mutant ERs, modified or not
      with diethyl pyrocarbonate (DEPC), a selective histidine reagent. Alanine
      substitution of H524 did not significantly change the association affinity
      constant (relative to OHT) of 17beta-dE(2), whereas those of RU, Ral, E(2), and 3
      dE(2) were decreased 3-fold, 14-fold, 24-fold, and 49-fold, respectively. Values
      of the two ligands available in radiolabeled form (E(2) and OHT) were correlated
      with the dissociation rate constants, which were increased 250-fold and 2-fold,
      respectively. The action of DEPC on wild-type ER led to a homogeneous ER
      population which still bound antiestrogens and 17beta-dE(2) with practically
      unchanged affinities (less than 4-fold decreases in relative affinity constants),
      while E(2) and 3-dE(2) displayed markedly decreased affinities (56-fold decrease
      for E(2)). Conversely, DEPC treatment of H524A mutant ER did not induce marked
      decreases in the relative affinities of any of the checked compounds (decreases
      </=3-fold). All of these effects appeared to involve H524 as the H516A mutant
      behaved as wild-type ER. These combined data relative to mutated or DEPC-modified
      ER converged to support that the interaction of 17beta/c-OH of ER ligands with
      H524 is strong for estrogens and weaker for antiestrogens, with quantitative or
      qualitative differences between the binding modes of the latter, as illustrated
      by RU and Ral. The abilities of E(2) and OHT to protect the various ER types
      against inactivation by DEPC were strikingly different: OHT totally prevented the
      effect of DEPC on wild-type, H516A, and H524A ERs, while E(2) only partially
      protected wild-type and H516A ERs (H516A ER > wild-type ER) and very weakly
      protected H524A ER. Molecular modeling was tentatively used to interpret the
      biochemical results.

PMID- 12069589
TI  - A unique type II topoisomerase mutant that is hypersensitive to a broad range of
      cleavage-inducing antitumor agents.
AB  - Bacteriophage T4 provides a useful model system for dissecting the mechanism of
      action of antitumor agents that target type II DNA topoisomerases. Many of these
      inhibitors act by trapping the cleavage complex, a covalent complex of enzyme and
      broken DNA. Previous analysis showed that a drug-resistant T4 mutant harbored two
      amino acid substitutions (S79F, G269V) in topoisomerase subunit gp52.
      Surprisingly, the single amino acid substitution, G269V, was shown to confer
      hypersensitivity in vivo to m-AMSA and oxolinic acid [Freudenreich, C. H., et al.
      (1998) Cancer Res. 58, 1260-1267]. We purified this G269V mutant enzyme and found
      it to be hypersensitive to a number of cleavage-inducing inhibitors including m
      AMSA, VP-16, mitoxantrone, ellipticine, and oxolinic acid. While the mutant
      enzyme did not exhibit altered DNA cleavage site specificity compared to the wild
      type enzyme, it did display an apparent 10-fold increase in drug-independent DNA
      cleavage. This suggests a novel mechanism of altered drug sensitivity in which
      the enzyme equilibrium has been shifted to favor the cleavage complex, resulting
      in an increase in the concentration of cleavage intermediates available to
      inhibitors. Mutations that alter drug sensitivities tend to cluster within two
      specific regions of all type II topoisomerases. Residue G269 of gp52 lies outside
      of these regions, and it is therefore not surprising that G269V leads to a unique
      mechanism of drug hypersensitivity. We believe that this mutant defines a new
      category of type II topoisomerase mutants, namely, those that are hypersensitive
      to all inhibitors that stabilize the cleavage complex.

PMID- 12069590
TI  - Relationship between the native-state hydrogen exchange and folding pathways of a
      four-helix bundle protein.
AB  - The hydrogen exchange behavior of a four-helix bundle protein in low
      concentrations of denaturant reveals some partially unfolded forms that are
      significantly more stable than the fully unfolded state. Kinetic folding of the
      protein, however, is apparently two-state in the absence of the accumulation of
      early folding intermediates. The partially unfolded forms are either as folded as
      or more folded than the rate-limiting transition state and appear to represent
      the major intermediates in a folding and unfolding reaction. These results are
      consistent with the suggestion that partially unfolded intermediates may form
      after the rate-limiting step for small proteins with apparent two-state folding
      kinetics.

PMID- 12069592
TI  - Determination of the stability of the noncovalent phospholipid transfer protein
      lipid complex by electrospray time-of-flight mass spectrometry.
AB  - Phosphatidylcholine transfer protein (PC-TP) containing different molecular
      species of PC and phosphatidylinositol transfer protein alpha (PI-TPalpha)
      containing either a PI, PC, or PG molecule were identified as intact complexes by
      nano-electrospray ionization time-of-flight mass spectrometry. The stability of
      these complexes in the gas phase was determined by elevating the cone voltage
      (cv) resulting in the appearance of the protein void of lipid. PC-TP containing a
      PC species carrying an sn-1 palmitoyl chain was less stable than PC-TP containing
      a PC species carrying an sn-1 stearoyl chain given that these complexes were
      dissociated for 50% at a cv of roughly 30 and 45 V, respectively. Different acyl
      chains on the sn-2 position did not lead to significant changes in stability of
      the complex. In the case of PI-TPalpha, the complexes containing PI and PG were
      dissociated for 50% at a cv of 100 V as compared to a cv of 40 V for the complex
      containing PC. We propose that this difference in stability is due to hydrogen
      bonds between the polar headgroup of PI and PG and the lipid-binding site of PI
      TPalpha. This may explain why PI-TPalpha preferentially binds PI from a membrane
      interface.

PMID- 12069591
TI  - Proteomic analysis of a highly active photosystem II preparation from the
      cyanobacterium Synechocystis sp. PCC 6803 reveals the presence of novel
      polypeptides.
AB  - A highly active oxygen-evolving photosystem II (PSII) complex was purified from
      the HT-3 strain of the widely used cyanobacterium Synechocystis sp. PCC 6803, in
      which the CP47 polypeptide has been genetically engineered to contain a
      polyhistidine tag at its carboxyl terminus [Bricker, T. M., Morvant, J., Masri,
      N., Sutton, H. M., and Frankel, L. K. (1998) Biochim. Biophys. Acta 1409, 50-57].
      These purified PSII centers had four manganese atoms, one calcium atom, and two
      cytochrome b(559) hemes each. Optical absorption and fluorescence emission
      spectroscopy as well as western immunoblot analysis demonstrated that the
      purified PSII preparation was devoid of any contamination with photosystem I and
      phycobiliproteins. A comprehensive proteomic analysis using a system designed to
      enhance resolution of low-molecular-weight polypeptides, followed by MALDI mass
      spectrometry and N-terminal amino acid sequencing, identified 31 distinct
      polypeptides in this PSII preparation. We propose a new nomenclature for the
      polypeptide components of PSII identified after PsbZ, which proceeds sequentially
      from Psb27. During this study, the polypeptides PsbJ, PsbM, PsbX, PsbY, PsbZ,
      Psb27, and Psb28 proteins were detected for the first time in a purified PSII
      complex from Synechocystis 6803. Five novel polypeptides were also identified in
      this preparation. They included the Sll1638 protein, which shares significant
      sequence similarity to PsbQ, a peripheral protein of PSII that was previously
      thought to be present only in chloroplasts. This work describes newly identified
      proteins in a highly purified cyanobacterial PSII preparation that is being
      widely used to investigate the structure, function, and biogenesis of this
      photosystem.

PMID- 12069593
TI  - Complexity of agonist- and cyclic AMP-mediated downregulation of the human beta 1
      adrenergic receptor: role of internalization, degradation, and mRNA
      destabilization.
AB  - Prolonged agonist exposure often induces downregulation of G protein-coupled
      receptors (GPCRs). Although downregulation of the prototypical beta(2)-adrenergic
      receptor (beta(2)AR) has been extensively studied, the underlying mechanisms have
      yet to be resolved. As even less is known about the beta(1)-subtype, we
      investigated the downregulation of human beta(1)AR stably expressed in Chinese
      hamster fibroblasts in response to the agonist isoproterenol or the cell
      permeable, chlorophenylthio-cAMP (CPT-cAMP). While either effector mediated
      decreases in both beta(1)AR binding activity and steady-state beta(1)AR mRNA
      levels, there were significant differences in their actions. Whereas agonist
      mediated downregulation of beta(1)AR followed first-order kinetics, that induced
      by CPT-cAMP was delayed for several hours and approximately 50% of the former.
      Furthermore, agonist but not CPT-cAMP induced beta(1)AR internalization, and
      inhibiting internalization also suppressed agonist-mediated downregulation. The
      latter, however, was more sensitive than the former to agonist concentration
      (EC(50) of 0.3 vs 48 nM). Thus, at < or =1 nM agonist, downregulation occurred
      without internalization and with a pattern similar to that mediated by CPT-cAMP.
      The amounts of beta(1)AR downregulated or internalized were proportional to
      initial receptor levels but reached saturation at approximately 2 and 3 pmol/mg
      of protein, respectively. The fate of beta(1)AR protein during downregulation was
      determined by immunoblotting with anti-C-terminal antibodies. In agonist-treated
      cells, beta(1)AR protein disappeared with time and without any immunoreactive
      degradation products. Agonist-mediated downregulation of the human beta(1)AR
      appears to be a complex process that consists of both agonist- and cAMP-specific
      components. The former involves both receptor internalization and degradation
      whereas the latter involves a reduction in receptor mRNA.

PMID- 12069594
TI  - Key motif to gain selectivity at the neuropeptide Y5-receptor: structure and
      dynamics of micelle-bound [Ala31, Pro32]-NPY.
AB  - The structure of [Ala(31), Pro(32)]-NPY, a neuropeptide Y mutant with selectivity
      for the NPY Y(5)-receptor (Cabrele, C., Wieland, H. A., Stidsen, C., Beck
      Sickinger, A. G., (2002) Biochemistry XX, XXXX-XXXX (companion paper)), has been
      characterized in the presence of the membrane mimetic dodecylphosphocholine (DPC)
      micelles using high-resolution NMR techniques. The overall topology closely
      resembles the fold of the previously described Y(5)-receptor-selective agonist
      [Ala(31), Aib(32)]-NPY (Cabrele, C., Langer, M., Bader, R., Wieland, H. A.,
      Doods, H. N., Zerbe, O., and Beck-Sickinger, A. G. (2000) J. Biol. Chem 275,
      36043-36048). Similar to wild-type neuropeptide Y (NPY) and [Ala(31), Aib(32)]
      NPY, the N-terminal residues Tyr(1)-Asp(16) are disordered in solution. Starting
      from residue Leu(17), an alpha helix extends toward the C-terminus. The decreased
      density of medium-range NOEs for the C-terminal residues resulting in larger RMSD
      values for the backbone atoms of Ala(31)-Tyr(36) indicates that the alpha helix
      has become interrupted through the [Ala(31), Pro(32)] mutation. This finding is
      further supported by (15)N-relaxation data through which we can demonstrate that
      the well-defined alpha helix is restricted to residues 17-31, with the C-terminal
      tetrapeptide displaying increased flexibility as compared to NPY. Surprisingly,
      increased generalized order parameter as well as decreased (3)J(HN)(alpha) scalar
      coupling constants reveal that the central helix is stabilized in comparison to
      wild-type NPY. Micelle-integrating spin labels were used to probe the mode of
      association of the helix with the membrane mimetic. The Y(5)-receptor-selective
      mutant and NPY share a similar orientation, which is parallel to the lipid
      surface. However, signal reductions due to efficient electron, nuclear spin
      relaxation were much less pronounced for the surface-averted residues in
      [Ala(31), Pro(32)]-NPY when compared to wild-type DPC-bound NPY. Only the signals
      of residues Asn(29) and Leu(30) were significantly more reduced in the mutant.
      The postulation of a different membrane binding mode of [Ala(31), Pro(32)]-NPY is
      further supported by the faster H/D exchange at the C-terminal amide protons. We
      conclude that arginine residues 33 and 35, which are believed to be directly
      involved in forming contacts to acidic receptor residues at the membrane-water
      interface, are no longer fixed in a well-defined conformation close to the
      membrane surface in [Ala(31), Pro(32)]-NPY.

PMID- 12069595
TI  - Ala31-Aib32: identification of the key motif for high affinity and selectivity of
      neuropeptide Y at the Y5-receptor.
AB  - The turn-inducing sequence Ala-Aib introduced into positions 31 and 32 of
      neuropeptide Y (NPY) and its analogues has been identified as the key structure
      for Y(5)-receptor selectivity. Analogues of NPY and PP/NPY chimera containing the
      motif Ala-Aib were prepared; these peptides turned out to be selective for the
      Y(5)-receptor. The affinity of the NPY-based peptides was in the range of 6-150
      nM, while the affinity of three (Ala-Aib)-containing PP/NPY chimera was in the
      range of 0.2-0.9 nM. The circular dichroism spectra of the Aib analogues in
      aqueous solution were all characteristic of an alpha helix; however, they had
      different intensities of the two negative bands at 220 and 208 nm. Affinity and
      selectivity for the Y(5)-receptor were correlated with the ratio of the
      ellipticity at 220 nm versus the one at 208 nm (R), which indicates the presence
      of a pronounced helix (R > 1) versus a less stabile one (R < 1). When R was in
      the range 0.74-0.96, the affinity at the Y(5)-receptor was in the range >5 nM,
      while there was complete loss of affinity at the Y(4)-receptor. R > 1.15 was
      associated with very high affinity at the Y(5)-receptor and weak affinity at the
      Y(4)-receptor. These results suggest that the selectivity of the Ala(31)-Aib(32)
      motif for the Y(5)-receptor derives from a specific conformation that must be
      correlated with the bioactive conformation of NPY at this subtype.

PMID- 12069596
TI  - Real-time monitoring of P-glycoprotein activation in living cells.
AB  - Extracellular acidification rates (ECARs) in response to eight different drugs
      activating or inhibiting the ATPase of P-glycoprotein (Pgp) were measured in real
      time by means of a Cytosensor microphysiometer in MDR1-transfected and
      corresponding wild-type cell lines, i.e., pig kidney cells (LLC-MDR1 and LLC-PK1)
      and mouse embryo fibroblasts (NIH-MDR-G185 and NIH3T3). The ECARs showed a bell
      shaped dependence on drug concentration (log scale) in transfected cells but were
      negligibly small in wild-type cells. The activation profiles (ECARs vs
      concentration) were analyzed in terms of a model assuming activation of Pgp
      ATPase with one and inhibition with two drug molecules bound. The kinetic
      constants [concentration of half-maximum activation (inhibition), K(i), and the
      maximum (minimum) transporter activity, V(i)] were in qualitative and
      quantitative agreement with those determined earlier for Pgp-ATPase activation
      monitored by phosphate release in inside-out cellular vesicles and in purified
      reconstituted systems, respectively. Furthermore, the ECARs correlated with the
      expression level of Pgp in the two different cell lines and were reduced in a
      concentration-dependent manner by cyclosporin A, a potent inhibitor of the Pgp
      ATPase. In contrast, treatment of cells with inhibitors of the Na(+)/H(+) or the
      Cl(-)/HCO(3)(-) exchanger did not reduce the ECARs. The micro-pH measurements
      provide for the first time direct evidence for a tight coupling between the rate
      of extracellular proton extrusion and intracellular phosphate release upon Pgp
      ATPase activation. They support a Pgp-mediated transport of protons from the site
      of ATP hydrolysis to the cell surface. Measurement of the ECARs could thus
      constitute a new method to conveniently analyze the kinetics of Pgp-ATPase
      activation in living cells.

PMID- 12069597
TI  - Nucleotide binding and nucleotide hydrolysis properties of the ABC transporter
      MRP6 (ABCC6).
AB  - Mutations in the MRP gene family member MRP6 cause pseudoxanthoma elasticum (PXE)
      in humans, a disease affecting elasticity of connective tissues. The normal
      function of MRP6, including its physiological substrate(s), remains unknown. To
      address these issues, recombinant rat Mrp6 (rMrp6) was expressed in the
      methylotrophic yeast Pichia pastoris. The protein was expressed in the membrane
      fraction as a stable 170 kDa protein. Its nucleotide binding and hydrolysis
      properties were investigated using the photoactive ATP analogue 8-azido-[alpha
      (32)P]ATP and compared to those of the drug efflux pump MRP1. rMrp6 can bind 8
      azido-[alpha-(32)P]ATP in a Mg(2+)-dependent and EDTA-sensitive fashion. Co(2+),
      Mn(2+), and Ni(2+) can also support 8-azido-[alpha-(32)P]ATP binding by rMrp6
      while Ca(2+), Cd(2+), and Zn(2+) cannot. Under hydrolysis conditions (at 37
      degrees C), the phosphate analogue beryllium fluoride (BeF(x)()) can stimulate
      trapping of the 8-azido-[alpha-(32)P]adenosine nucleotide in rMrp6 (and in MRP1)
      in a divalent cation-dependent and temperature-sensitive fashion. This suggests
      active ATPase activity, followed by trapping and photo-cross-linking of the 8
      azido-[alpha-(32)P]ADP to the protein. By contrast to MRP1, orthovanadate
      stimulated nucleotide trapping in rMrp6 does not occur in the presence of Mg(2+)
      but can be detected with Ni(2+) ions, suggesting structural and/or functional
      differences between the two proteins. The rMrp6 protein can be specifically
      photolabeled by a fluorescent photoactive drug analogue, [(125)I]-IAARh123, with
      characteristics similar to those previously reported for MRP1 (1), and this
      photolabeling of rMrp6 can be modulated by several structurally unrelated
      compounds. The P. pastoris expression system has allowed demonstration of ATP
      binding and ATP hydrolysis by rMrp6. In addition to providing large amounts of
      active protein for detailed biochemical studies, this system should also prove
      useful to identify potential rMrp6 substrates in [(125)I]-IAARh123 photolabeling
      competition studies, as well as to study the molecular basis of PXE mutations,
      which are most often found in the NBD2 of MRP6.

PMID- 12069598
TI  - Transbilayer asymmetry of phospholipids in the plasma membrane regulates
      exocytotic release in mast cells.
AB  - To investigate the role of the asymmetric distribution of phospholipids of the
      plasma membrane in exocytosis, we examined the effects of disruption of this
      asymmetrical distribution of lipids on exocytotic release from mast cells (RBL
      2H3). Lipid scramblase, which is activated by divalent cations and catalyzes the
      transbilayer movement of phospholipids, was overexpressed in mast cells.
      Exogenous lipid scramblase was expressed in the plasma membrane and the
      cytoplasm. Activation of scramblase by divalent cations disrupted the
      asymmetrical distribution of phospholipids in the plasma membrane. Exocytotic
      release induced by calcium ionophore and phorbol ester was significantly
      inhibited in the cells transfected with wild-type scramblase. This inhibition was
      observed with time lag of about 5 min. Furthermore, when the asymmetric
      distribution of lipids was disrupted before induction of exocytosis, the
      inhibition of exocytotic release was obvious from the beginning without time lag.
      These results suggest that the asymmetric distribution of phospholipids in the
      plasma membrane plays an essential role in fusion between secretory granules and
      the plasma membrane. This finding also demonstrates that the transbilayer
      asymmetry of phospholipids regulates exocytosis and gives a new insight into the
      significance of lipid asymmetry in the plasma membrane.

PMID- 12069600
TI  - Ligand-induced differences in secondary structure of the Vibrio parahaemolyticus
      Na+/galactose cotransporter.
AB  - A detailed structural study of the prokaryotic sodium/galactose transporter
      (vSGLT) from Vibrio parahaemolyticus using attenuated total reflection Fourier
      transform infrared (ATR-FTIR) spectroscopy reveals stepwise increases in alpha
      helicity upon binding of sodium and D-galactose. These increases in helicity
      correlate with decreases in beta-structural elements. The changes are accompanied
      by stepwise reductions in the degree of H/D exchange (HDX), suggesting reduced
      accessibility of water to the protein backbone. The data demonstrate discrete
      conformational changes from one intermediate to the next during the catalytic
      cycle of the protein and are interpreted in a model of the symport reaction
      mechanism.

PMID- 12069601
TI  - Three G.C base pairs required for the efficient aminoacylation of tRNATrp by
      tryptophanyl-tRNA synthetase from Bacillus subtilis.
AB  - Acceptor stem is an essential region in the recognition of tRNAs by their cognate
      aminoacyl-tRNA synthetase. In this study, a library containing 20 nt random
      region and tryptophanyl-tRNA synthetase (TrpRS) from Bacillus subtilis were used
      for in vitro selection to find a new structural feature in the tRNA(Trp) acceptor
      stem sequence that is required for B. subtilis TrpRS recognition. After three
      rounds of selection, the TrpRS binding RNAs dominate the RNA pool. The aptamers
      share a common structure of three G.C base pairs, which was also found in the
      acceptor stem of wild-type B. subtilis tRNA(Trp). A series of tRNA(Trp) variants
      was prepared by in vitro transcription, and their efficiencies of
      tryptophanylation (k(cat)/K(M)) were measured with the aid of TrpRS from B.
      subtilis. The mutants that possess the three G.C base pairs and G73 discriminator
      base exhibit almost the same aminoacylation efficiencies as B. subtilis
      tRNA(Trp), while the G73 discriminator base itself cannot confer efficient
      aminoacylation to the tRNA(Trp) molecule. Thus, these three base pairs (G2.C71,
      G3.C70, and G4.C69) in the B. subtilis tRNA(Trp) acceptor stem were established
      to be new identity elements, and their importance was between the previously
      characterized major element G73 and minor elements A1/U72 and G5/C68. The minimum
      set of identity elements that is required to confer efficient aminoacylation by
      B. subtilis TrpRS included G73, G2.C71, G3.C70, and G4.C69.

PMID- 12069599
TI  - Nicotinamide is not a substrate of the facilitative hexose transporter GLUT1.
AB  - It has been proposed that GLUT1, a membrane protein that transports hexoses and
      the oxidized form of vitamin C, dehydroascorbic acid, is also a transporter of
      nicotinamide (Sofue, M., Yoshimura, Y., Nishida, M., and Kawada, J. (1992)
      Biochem. J. 288, 669-674). To ascertain this, we studied the transport of 2-deoxy
      D-glucose, 3-O-methyl-D-glucose, and nicotinamide in human erythrocytes and right
      side-out and inside-out erythrocyte membrane vesicles. The transport of
      nicotinamide was saturable, with a K(M) for influx and efflux of 6.1 and 6.2 mM,
      respectively. We found that transport of the hexoses was not competed by
      nicotinamide in both the erythrocytes and the erythrocyte vesicles. Likewise, the
      transport of nicotinamide was not affected by hexoses or by inhibitors of glucose
      transport such as cytochalasin B, genistein, and myricetin. On the other hand,
      nicotinamide blocked the binding of cytochalasin B to human erythrocyte membranes
      but did so in a noncompetitive manner. Using GLUT1-transfected CHO cells, we
      demonstrated that increased expression of GLUT1 was paralleled by a corresponding
      increase in hexose transport but that there were no changes in nicotinamide
      transport. Moreover, nicotinamide failed to affect the transport of hexoses in
      both control and GLUT1-transfected CHO cells. Therefore, our results indicates
      that GLUT1 does not transport nicotinamide, and we propose instead the existence
      of other systems for the translocation of nicotinamide across cell membranes.

PMID- 12069602
TI  - Endogenous DNA lesions can inhibit the binding of the AP-1 (c-Jun) transcription
      factor.
AB  - The repair of DNA damage, caused by both endogenous and exogenous sources, is
      necessary to remove lesions that either miscode or block DNA or RNA polymerases.
      We propose that damage also must be repaired to maintain sequence-specific DNA
      protein interactions. In this paper, we have systematically studied two lesions
      that interfere with one important DNA landmark, the thymine methyl group.
      Oxidation of the thymine methyl group in DNA generates 5-hydroxymethyluracil
      (HmU) whereas the misincorporation of dUMP into DNA generates uracil (U),
      replacing the methyl group with a hydrogen. Both substitutions are shown to
      inhibit binding of the AP-1 (c-Jun) transcription factor. The energy cost of the
      perturbation, approximately 0.4 kcal/mol, is similar in magnitude for both U and
      HmU substitutions and is additive when multiple substitutions are present. A
      third lesion, substitution of the central C:G base pair of the AP-1 DNA binding
      domain with the pro-mutagenic U:G mispair, unexpectedly increases AP-1 binding,
      allowing the transcription factor to interfere with uracil DNA glycosylase
      activity. Our results support the hypothesis that an additional role for DNA
      repair systems is to maintain the integrity of sequence-specific DNA-protein
      interactions, a role of particular importance in long-lived organisms.

PMID- 12069603
TI  - Metal ion requirements for structure and catalysis of an RNA ligase ribozyme.
AB  - The class I ligase, a ribozyme previously isolated from random sequence,
      catalyzes a reaction similar to RNA polymerization, positioning its 5'-nucleotide
      via a Watson-Crick base pair, forming a 3',5'-phosphodiester bond between its 5'
      nucleotide and the substrate, and releasing pyrophosphate. Like most ribozymes,
      it requires metal ions for structure and catalysis. Here, we report the ionic
      requirements of this self-ligating ribozyme. The ligase requires at least five
      Mg(2+) for activity and has a [Mg(2+)](1/2) of 70-100 mM. It has an unusual
      specificity for Mg(2+); there is only marginal activity in Mn(2+) and no
      detectable activity in Ca(2+), Sr(2+), Ba(2+), Zn(2+), Co(2+), Cd(2+), Pb(2+),
      Co(NH(3))(6)(3+), or spermine. All tested cations other than Mg(2+), including
      Mn(2+), inhibit the ribozyme. Hill analysis in the presence of inhibitory cations
      suggested that Ca(2+) and Co(NH(3))(6)(3+) inhibit by binding at least two sites,
      but they appear to productively fill a subset of the required sites. Inhibition
      is not the result of a significant structural change, since the ribozyme assumes
      a nativelike structure when folded in the presence of Ca(2+) or Co(NH(3))(6)(3+),
      as observed by hydroxyl-radical mapping. As further support for a nativelike fold
      in Ca(2+), ribozyme that has been prefolded in Ca(2+) can carry out the self
      ligation very quickly upon the addition of Mg(2+). Ligation rates of the
      prefolded ribozyme were directly measured and proceed at 800 min(-1) at pH 9.0.

PMID- 12069604
TI  - Molecular recognition by the Candida albicans group I intron: tertiary
      interactions with an imino G.A pair facilitate binding of the 5' exon and lower
      the KM for guanosine.
AB  - A G.A pair at position -5 in the P1 helix of the Candida albicans ribozyme
      contributes to tertiary binding of the 5' exon substrate [Disney, M. D.,
      Haidaris, C. G., and Turner, D. H. (2001) Biochemistry 40, 6507-6519]. Here, the
      G in the G.A pair is replaced with inosine (I) in both semisynthetic ribozymes
      and oligonucleotide mimics of the internal guide sequence. Comparisons of
      oligonucleotide binding affinity for these and other sequences indicate that the
      G.A pair is in an imino conformation where the exocyclic amine of G contributes
      approximately 1.4 kcal/mol to tertiary interactions that help dock the ribozyme's
      P1 helix. Furthermore, replacement of the G.A pair with a G-C pair produces less
      favorable interactions with the 2'-hydroxyl group at the -3 position and a less
      favorable K(M) for pG in a ribozyme-catalyzed transesterification reaction. These
      results are also consistent with the G.A pair promoting docking of the P1 helix
      into the catalytic core. Evidently, tertiary interactions with the exocyclic
      amino group of a G in a single G.A pair can increase the equilibrium constant for
      tertiary folding of RNA by roughly 10-fold at 37 degrees C. Results with a G.U or
      G.G pair replacing the G.A pair at the -5 position suggest similar tertiary
      interactions with these pairs.

PMID- 12069605
TI  - Properties of the recombinant ferredoxin-dependent glutamate synthase of
      Synechocystis PCC6803. Comparison with the Azospirillum brasilense NADPH
      dependent enzyme and its isolated alpha subunit.
AB  - The properties of the recombinant ferredoxin-dependent glutamate synthase of
      Synechocystis PCC6803 were determined by means of kinetic and spectroscopic
      approaches in comparison to those exhibited by the bacterial NADPH-dependent
      enzyme form. The ferredoxin-dependent enzyme was found to be similar to the
      bacterial glutamate synthase alpha subunit with respect to cofactor content (one
      FMN cofactor and one [3Fe-4S] cluster per enzyme subunit), overall absorbance
      properties, and reactivity of the FMN N(5) position with sulfite, as expected
      from the similar primary structure of ferredoxin-dependent glutamate synthase and
      of the bacterial NADPH-dependent glutamate synthase alpha subunit. The ferredoxin
      and NADPH-dependent enzymes were found to differ with respect to the apparent
      midpoint potential values of the FMN cofactor and of the [3Fe-4S] cluster, which
      are less negative in the ferredoxin-dependent enzyme form. This feature is, at
      least in part, responsible for the efficient oxidation of L-glutamate catalyzed
      by this enzyme form, but not by the bacterial NADPH-dependent counterpart. At
      variance with earlier reports on ferredoxin-dependent glutamate synthase, in the
      Synechocystis enzyme the [3Fe-4S] cluster is not equipotential with the flavin
      cofactor. The present studies also demonstrated that binding of reduced
      ferredoxin to ferredoxin-dependent glutamate synthase is essential in order to
      activate reaction steps such as glutamine binding, hydrolysis, or ammonia
      transfer from the glutamine amidotransferase site to the glutamate synthase site
      of the enzyme. Thus, ferredoxin-dependent glutamate synthase seems to control and
      coordinate catalytic activities taking place at its subsites by regulating the
      reactions of the glutamine amidotransferase site. Association with reduced
      ferredoxin appears to be necessary, but not sufficient, to trigger the required
      activating conformational changes.

PMID- 12069606
TI  - Contributions of active site residues to the partial and overall catalytic
      activities of human S-adenosylhomocysteine hydrolase.
AB  - Residues glutamate 156 (E156), aspartate 190 (D190), asparagine 181 (N181),
      lysine 186 (K186), and asparagine 191 (N191) in the active site of S
      adenosylhomocysteine (AdoHcy) hydrolase have been mutated to alanine (A). AdoHcy
      hydrolase achieves catalysis of AdoHcy hydrolysis to adenosine (Ado) and
      homocysteine (Hcy) by means of a redox partial reaction (3'-oxidation of AdoHcy
      at the beginning and 3'-reduction of Ado at the end of the catalytic cycle)
      spanning an elimination/addition partial reaction (elimination of Hcy from the
      oxidized substrate and addition of water to generate the oxidized product), with
      the enzyme in an open NAD(+) form in the ligand-free state and in a closed NADH
      form during the elimination/addition partial reaction. Mutation K186A reduces the
      rate of a model enzymatic reaction for the redox partial reaction by a factor of
      280000 and the rate of a model reaction for the elimination/addition partial
      reaction by a factor of 24000, consistent with a primary catalytic role in both
      partial reactions as a proton donor/acceptor at the 3'-OH/3'-keto center.
      Secondary roles for N181 and N191 in localizing the flexible side chain of K186
      in a catalytically effective position are supported by rate reduction factors for
      N181A of 2500 (redox) and 240 (elimination/addition) and for N191A of 730 (redox)
      and 340 (elimination/addition). A role of D190 in orienting the substrate for
      effective transition-state stabilization is consistent with rate reduction
      factors of 1300 (redox) and 30 (elimination/addition) for D190A. Residue E156 may
      act to maintain K186 in the desired protonation state: rate deduction factors are
      1100 (redox) and 70 (elimination/addition). The mutational increases in free
      energy barriers for k(cat)/K(M) are described by a linear combination of the
      effects for the partial reactions with the coefficients equal to the fractional
      degree that each partial reaction determines the rate for k(cat)/K(M). A similar
      linear equation for k(cat) overestimates the barrier increase by a uniform 5
      kJ/mol, probably reflecting reactant-state stabilization by the wild-type enzyme
      that is abolished by the mutations.

PMID- 12069607
TI  - Characterization of the nucleation step and folding of a collagen triple-helix
      peptide.
AB  - Peptide T1-892 is a triple-helical peptide designed to include two distinct
      domains: a C-terminal (Gly-Pro-Hyp)(4) sequence, together with an N-terminal 18
      residue sequence from the alpha1(I) chain of type I collagen. Folding experiments
      of T1-892 using CD spectroscopy were carried out at varying concentrations and
      temperatures, and fitting of kinetic models to the data was used to obtain
      information about the folding mechanism and to derive rate constants. Proposed
      models include a heterogeneous population of monomers with respect to cis-trans
      isomerization and a third-order folding reaction from competent monomer to the
      triple helix. Fitting results support a nucleation domain composed of all or most
      of the (Gly-Pro-Hyp)(4) sequence, which must be in trans form before the monomer
      is competent to initiate triple-helix formation. The folding of competent monomer
      to a triple helix is best described by an all-or-none third-order reaction. The
      temperature dependence of the third-order rate constant indicates a negative
      activation energy and provides information about the thermodynamics of the
      trimerization step. These CD studies complement NMR studies carried out on the
      same peptide at high concentrations, illustrating how the rate-limiting folding
      step is affected by changes in concentration. This sequence preference of
      repeating Gly-Pro-Hyp units for the initiation of triple-helix formation in
      peptide T1-892 may be related to features in the triple-helix folding of
      collagens.

PMID- 12069608
TI  - Elucidation of factors responsible for enhanced thermal stability of proteins: a
      structural genomics based study.
AB  - Understanding the molecular basis for the enhanced stability of proteins from
      thermophiles has been hindered by a lack of structural data for homologous pairs
      of proteins from thermophiles and mesophiles. To overcome this difficulty,
      complete genome sequences from 9 thermophilic and 21 mesophilic bacterial genomes
      were aligned with protein sequences with known structures from the protein data
      bank. Sequences with high homology to proteins with known structures were chosen
      for further analysis. High quality models of these chosen sequences were obtained
      using homology modeling. The current study is based on a data set of models of
      900 mesophilic and 300 thermophilic protein single chains and also includes 178
      templates of known structure. Structural comparisons of models of homologous
      proteins allowed several factors responsible for enhanced thermostability to be
      identified. Several statistically significant, specific amino acid substitutions
      that occur going from mesophiles to thermophiles are identified. Most of these
      are at solvent-exposed sites. Salt bridges occur significantly more often in
      thermophiles. The additional salt bridges in thermophiles are almost exclusively
      in solvent-exposed regions, and 35% are in the same element of secondary
      structure. Helices in thermophiles are stabilized by intrahelical salt bridges
      and by an increase in negative charge at the N-terminus. There is an approximate
      decrease of 1% in the overall loop content and a corresponding increase in
      helical content in thermophiles. Previously overlooked cation-pi interactions,
      estimated to be twice as strong as ion-pairs, are significantly enriched in
      thermophiles. At buried sites, statistically significant hydrophobic amino acid
      substitutions are typically consistent with decreased side chain conformational
      entropy.

PMID- 12069609
TI  - Structure-function studies of analogues of parathyroid hormone (PTH)-1-34
      containing beta-amino acid residues in positions 11-13.
AB  - The 1-34 N-terminal fragments of human parathyroid hormone (PTH) and PTH-related
      protein (PTHrP) elicit the full spectrum of bone-relevant activities
      characteristic of the intact hormones. The structural elements believed to be
      required for receptor binding and biological activity are two helical segments,
      one N-terminal and one C-terminal, connected by hinges or flexible points located
      around positions 12 and 19. To test this hypothesis, we synthesized and
      characterized the following analogues of PTH-(1-34), each containing single or
      double substitutions with beta-amino acid residues around the putative hinge
      located at position 12: I. [Nle(8,18),beta-Ala(11,12),Nal(23),Tyr(34)]bPTH-(1
      34)NH(2); II. [Nle(8,18),beta-Ala(12,13),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); III.
      [Nle(8,18),beta-Ala(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); IV. [Nle(8,18),beta
      hLeu(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); V. [Nle(8,18),beta-Ala(12),
      Nal(23),Tyr(34)]bPTH-(1-34)NH(2); VI. [Nle(8,18),beta-Ala(13),
      Nal(23),Tyr(34)]bPTH-(1-34)NH(2) (beta-hLeu = beta-homo-leucine; beta-Ala = beta
      alanine; Nal = L-2-naphthyl-alanine; Nle = norleucine). Analogues I and III
      exhibit very low binding affinity and are devoid of adenylyl cyclase activity.
      Analogue II, despite its very low binding capacity is an agonist. Biological
      activity and binding capacity are partially restored in analogue IV, and
      completely restored in analogues V and VI. The conformational properties of the
      analogues were investigated in aqueous solution containing dodecylphosphocholine
      (DPC) micelles as a membrane-mimetic environment using CD, 2D-NMR, and molecular
      dynamics calculations. All peptides fold partially into the alpha-helical
      conformation in the presence of DPC micelles, with a maximum helix content in the
      range of 30-35%. NMR analysis reveals the presence of two helical segments, one N
      terminal and one C-terminal, as a common structural motif in all analogues.
      Incorporation of beta-Ala dyads at positions 11,12 and 12,13 in analogues I and
      II, respectively, enhances the conformational disorder in this portion of the
      sequence but also destabilizes the N-terminal helix. This could be one of the
      possible reasons for the lack of biological activity in these analogues. The
      partial recovery of binding affinity and biological activity in analogue IV,
      compared to the structurally similar analogue III, is clearly the consequence of
      the reintroduction of Leu side-chain of the native sequence. In the fully active
      analogues V and VI, the helix stability at the N-terminus is further increased.
      Taken together, these results stress the functional importance of the
      conformational stability of the helical activation domain in PTH-(1-34). Contrary
      to expectation, insertion of a single beta-amino acid residue in positions 11,
      12, or 13 in analogues III-VI does not favor a disordered structure in this
      portion of the sequence.

PMID- 12069610
TI  - Specific effects of chloride on the photocycle of E194Q and E204Q mutants of
      bacteriorhodopsin as measured by FTIR spectroscopy.
AB  - Low-temperature Fourier transform infrared spectroscopy has been used to study
      mutants of Glu194 and Glu204, two amino acids that are involved in proton release
      to the extracellular side of bacteriorhodopsin. Difference spectra of films of
      E194Q, E204Q, E194Q/E204Q, E9Q/E194Q/E204Q, and E9Q/E74Q/E194Q/E204Q at 243, 277,
      and 293 K and several pH values were obtained by continuous illumination. A
      specific effect of Cl(-) ions was found for the mutants, promoting a N-like
      intermediate at alkaline pH and an O' intermediate at neutral or acid pH. The
      apparent pK(a) of Asp85 in the M intermediate was found to be decreased for E194Q
      in the presence of Cl(-) (pK(a) of 7.6), but it was unchanged for E204Q, as
      compared to wild-type. In the absence of Cl(-) (i.e., in the presence of
      SO(4)(2)(-)), mutation of Glu194 or of Glu204 produces M- (or M(N), M(G))-like
      intermediates under all of the conditions examined. The absence of N, O, and O'
      intermediates suggests a long-range effect of the mutation. Furthermore, it is
      suggested that Cl(-) acts by reaching the interior of the protein, rather than
      producing surface effects. The effect of low water content was also examined, in
      the presence of Cl(-). Similar spectra corresponding to the M(1) intermediate
      were found for dry samples of both mutants, indicating that the effects of the
      mutations or of Cl(-) ions are confined to the second part of the photocycle. The
      water O-H stretching data further confirms altered photocycles and the effect of
      Cl(-) on the accumulation of the N intermediate.

PMID- 12069611
TI  - Chlorophyll triplet states associated with photosystem II of thylakoids.
AB  - The analysis of FDMR thylakoid spectra, determined at multiple emission
      wavelengths, by a global decomposition technique, has revealed the presence of
      three previously undescribed triplet populations at emission wavelengths
      characteristic of Photosystem II chlorophyll/protein complexes. Their zero-field
      splitting parameters have been determined in order to compare them with the well
      studied PSII recombination triplet state. None of these triplets have the zero
      field splitting parameters characteristic of the recombination triplet and are
      therefore probably not generated directly in the reaction center. On the basis of
      their microwave-induced emission spectra, it is suggested that two are probably
      generated in the core complex(es) while the third may be generated in the
      external antenna. These triplets are formed under nonreducing redox conditions,
      when the recombination triplet is undetectable. It is suggested that they may be
      involved in the photoinhibitory damage of Photosystem II. The triplet-minus
      singlet spectrum associated with the recombination triplet state has been
      determined for thylakoids after reduction of the secondary acceptors. Its main
      peak is at 685 nm, slightly red shifted with respect to earlier reports, with a
      weak signal, of opposite sign at approximately 675 nm. The 685 nm peak indicates
      that at cryogenic temperatures, the triplet is located on the long-wavelength
      chlorophyll state present in the reaction center complex of Photosystem II
      (D1.D2.Cytb(559) complex). From the absence of a clear structure in the 680 nm
      absorption region, this long-wavelength absorbing state does not appear to be
      strongly coupled to P(680), though it must be associated with one of the "inner
      core" pigments recently identified in the photosystem II crystallographic
      structure [Zouni et al. (2001) Nature 408, 739-743].

PMID- 12069612
TI  - Catalytic phosphorylation of Na,K-ATPase drives the outward movement of its
      cation-binding H5-H6 hairpin.
AB  - The Na,K-ATPase undergoes conformational transitions during its catalytic cycle
      that mediate energy transduction between the phosphorylation and cation-binding
      sites. Structure-function studies have shown that transmembrane segments H5 and
      H6 in the alpha subunit of the enzyme participate in cation binding and
      transport. The Ca-ATPase crystal structure indicates that the H5 helix extends
      into the cytoplasmic ATP binding domain, finishing 4-5 A from the phosphorylation
      site. Here, we test whether the phosphorylation of the Na,K-ATPase leads to
      conformational changes in the cation-binding H5-H6 hairpin. Using as background
      an enzyme where all wild-type Cys in the transmembrane region were replaced, Cys
      were introduced in the joining loop and extracellular ends of H5 and H6. Mutated
      proteins were expressed in COS cells and probed with Hg(2+), [2
      (trimethylammonium)ethyl]methanethiosulfonate (MTSET), and biotin-maleimide,
      applied to the extracellular media while placing the cells in two different media
      (K-medium and Na-medium). We assumed that under these treatment conditions most
      of the enzyme would be in one of two predominant conformations: E1 (K-medium) and
      E2P (Na-medium). The extent of enzyme inactivation by Hg(2+) or MTSET treatment
      was dependent on the targeted position; i.e., proteins carrying Cys in the
      outermost positions were more affected by treatment. Moreover, in the case of
      proteins carrying Cys at positions 785, 787, and 797, driving the enzyme to
      phosphorylated conformations (Na-media) led to a larger inactivation. Similarly,
      biotinylation of introduced Cys was also influenced by the enzyme conformation,
      with a larger extent of modification after treatment of cells in the Na-medium
      (E2P form). These results can be explained by the enzyme phosphorylation driving
      the outward movement of the H5 helix. Thus, they provide experimental evidence
      for a structure-function mechanism where, via H5, enzyme phosphorylation leads to
      a conformational change at the cation-binding site and the consequent cation
      translocation.

PMID- 12069613
TI  - Inhibition of apolipoprotein E-related neurotoxicity by glycosaminoglycans and
      their oligosaccharides.
AB  - Apolipoprotein E (apoE) has been genetically linked to late-onset Alzheimer's
      disease (AD). The role of this lipid-transport protein in AD remains to be
      established. One hypothesis is that apoE, particularly the apoE4 isoform, may
      have neurotoxic effects as demonstrated using apoE-related synthetic peptides and
      the N-terminal fragment of apoE. ApoE is a heparan-sulfate binding protein, and
      apoE peptide neurotoxicity can be blocked by heparin and prevented by degrading
      heparan sulfate or inhibiting its biosynthesis. The possibility that heparin
      inhibition of toxicity is mediated by a specific oligosaccharide sequence was
      investigated using a bioassay to determine the inhibition of apoE peptide
      toxicity by glycosaminoglycans and purified glycosaminoglycan oligosaccharides.
      Studies on modified heparins showed that the presence of N-sulfo groups and
      either 2- or 6-O sulfo groups were required for inhibition of toxicity. Heparin
      oligosaccharides with eight or more saccharide residues with seven O-sulfo groups
      and four N-sulfo groups exhibited potent inhibition. Larger oligosaccharides, and
      heparin and heparan sulfate polymers, afforded comparable, or somewhat better,
      protective effects but also caused clumping and detachment of cells when
      administrated alone.

PMID- 12069614
TI  - Identification of bovine heart cytochrome c oxidase subunits modified by the
      lipid peroxidation product 4-hydroxy-2-nonenal.
AB  - Bovine heart cytochrome c oxidase (CcO) was inactivated by the lipid peroxidation
      product 4-hydroxy-2-nonenal (HNE) in a time- and concentration-dependent manner
      with pseudo-first-order kinetics. Cytochrome c oxidase electron transport
      activity decreased by as much as 50% when the enzyme was incubated for 2 h at
      room temperature with excess HNE (300-500 microM). HNE-modified CcO subunits were
      identified by two mass spectrometric methods: electrospray ionization mass
      spectrometry (ESI/MS) and matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOF/MS). All of the experimentally determined
      molecular masses were in excellent agreement with published sequence values with
      an accuracy of approximately 1 part per 10000 mass units for subunits smaller
      than 20 kDa and approximately 1 part per 1000 mass units for the three subunits
      larger than 20 kDa. Both MS methods detected six CcO subunits with an increased
      mass of 156 Da after reaction with HNE (subunits II, IV, Vb, VIIa, VIIc, and
      VIII); this result indicates a single Michael-type reaction site on either a
      lysine or histidine residue within each subunit. Reaction of HNE with either
      subunit VIIc or subunit VIII (modified approximately 30% and 50-75%,
      respectively) must be responsible for CcO inhibition. None of the other subunits
      were modified more than 5% and could not account for the observed loss of
      activity. Reaction of HNE with His-36 of subunit VIII is most consistent with the
      approximately 50% inhibition of CcO: (1) subunit VIII is modified more than any
      other subunit by HNE; (2) the time dependence of subunit VIII modification is
      consistent with the percent inhibition of CcO; (3) His-36 was identified as the
      HNE-modified amino acid residue within subunit VIII by tandem MS analysis.

PMID- 12069615
TI  - Molecular dynamics simulations of biomolecules.

PMID- 12069616
TI  - Molecular dynamics and NMR spin relaxation in proteins.
AB  - Molecular dynamics simulations often play a central role in the analysis of
      biomolecular NMR data. The focus here is on NMR spin-relaxation, which can
      provide unique insights into the time-dependence of conformational fluctuations,
      especially on picosecond to nanosecond time scales which can be directly probed
      by simulations. A great deal has been learned from such simulations about the
      general nature of such motions and their impact on NMR observables. In principle,
      relaxation measurements should also provide valuable benchmarks for judging the
      quantitative accuracy of simulations, but there are a variety of experimental and
      computational obstacles to making useful direct comparisons. It seems likely that
      simulations on time scales that are just now becoming generally feasible may
      provide important new information on internal motions, overall rotational
      diffusion, and the coupling between internal and rotational motion. Such
      information could provide a sound foundation for a new generation of detailed
      interpretation of NMR spin-relaxation results.

PMID- 12069617
TI  - Molecular dynamics of acetylcholinesterase.
AB  - Molecular dynamics simulations are leading to a deeper understanding of the
      activity of the enzyme acetylcholinesterase. Simulations have shown how breathing
      motions in the enzyme facilitate the displacement of substrate from the surface
      of the enzyme to the buried active site. The most recent work points to the
      complex and spatially extensive nature of such motions and suggests possible
      modes of regulation of the activity of the enzyme.

PMID- 12069618
TI  - The incorporation of quantum effects in enzyme kinetics modeling.
AB  - We present an overview of new procedures for including quantum mechanical effects
      in enzyme kinetics. Quantum effects are included in three ways: (1) The
      electronic structure of the atoms in the catalytic center is treated quantum
      mechanically in order to calculate a realistic potential energy surface for the
      bond rearrangement process. (2) The discrete nature of quantum mechanical
      vibrational energies is incorporated in the treatment of nuclear motion for
      computing the potential of mean force. (3) Multidimensional tunneling
      contributions are included. These procedures are illustrated by applications to
      proton abstractions catalyzed by enolase and methylamine dehydrogenase and
      hydride-transfer reactions by alcohol dehydrogenase and xylose isomerase.

PMID- 12069619
TI  - Simulations of nucleic acids and their complexes.
AB  - Recent years have seen considerable progress in simulations of nucleic acids.
      Improvements in force fields, simulation techniques and protocols, and increasing
      computer power have all contributed to making nanosecond-scale simulations of
      both DNA and RNA commonplace. The results are already helping to explain how
      nucleic acids respond to their environment and to their base sequence and to
      reveal the factors underlying recognition processes by probing biologically
      important nucleic acid-protein interactions and medically important nucleic acid
      drug complexation. This Account summarizes methodological progress and
      applications of molecular dynamics to nucleic acids over the past few years and
      tries to identify remaining challenges.

PMID- 12069620
TI  - Ligand binding affinities from MD simulations.
AB  - Simplified free energy calculations based on force field energy estimates of
      ligand-receptor interactions and thermal conformational sampling have emerged as
      a useful tool in structure-based ligand design. Here we give an overview of the
      linear interaction energy (LIE) method for calculating ligand binding free
      energies from molecular dynamics simulations. A notable feature is that the
      binding energetics can be predicted by considering only the intermolecular
      interactions of the ligand in the associated and dissociated states. The
      approximations behind this approach are examined, and different parametrizations
      of the model are discussed. LIE-type methods appear particularly promising for
      computational "lead optimization". Recent applications to protein-protein
      interactions and ion channel blocking are also discussed.

PMID- 12069621
TI  - Computational studies of the gramicidin channel.
AB  - Ion channels are highly specific membrane-spanning protein structures which serve
      to facilitate the passage of selected ions across the lipid barrier. In the past
      decade, molecular dynamics simulations based on atomic models and realistic
      microscopic interactions with explicit solvent and membrane lipids have been used
      to gain insight into the function of these complex systems. These calculations
      have considerably expanded our view of ion permeation at the microscopic level.
      This Account will mainly focus on computational studies of the gramicidin A
      channel, one of the simplest and best characterized molecular pore.

PMID- 12069622
TI  - Solvation and hydration of proteins and nucleic acids: a theoretical view of
      simulation and experiment.
AB  - Many theoretical, computational, and experimental techniques recently have been
      successfully used for description of the solvent distribution around
      macromolecules. In this Account, we consider recent developments in the areas of
      protein and nucleic acid solvation and hydration as seen by experiment, theory,
      and simulations. We find that in most cases not only the general phenomena of
      solvation but even local hydration patterns are more accurately discussed in the
      context of water distributions rather than individual molecules of water. While a
      few localized or high-residency waters are often associated with macromolecules
      in solution (or crystals from aqueous liquors), these are readily and accurately
      included in this more general description. The goal of this Account is to review
      the theoretical models used for the description of the interfacial solvent
      structure on the border near DNA and protein molecules. In particular, we hope to
      highlight the progress in this field over the past five years with a focus on
      comparison of simulation and experimental results.

PMID- 12069623
TI  - Molecular dynamics simulations of biological reactions.
AB  - This review considers the author perspective on the emergence of molecular
      dynamics (MD) simulations of biological processes. It starts with the 1976
      simulation of the primary event in rhodopsin, moves to the earliest simulations
      of enzymatic reactions and electron transfer reactions and ends up with recent
      simulations of proton translocations and ion transport in proteins. The emphasis
      is placed on our progress in simulations of actual biological reactions and
      functional properties, rather than on studies of general properties such as
      structure and thermal motions. In most cases it has been possible to develop
      special strategies that capture the relevant dynamics of the given biological
      process. The predictive power of our early simulations of fast biological process
      (e.g. vision and photosynthesis) and the insight obtained from these studies is
      pointed out. Critical examinations of dynamical effects in different biological
      processes is reviewed. This includes the finding that dynamical effects are
      unlikely to contribute significantly to enzyme catalysis or to other processes
      with significant activation barriers. Even in the case of ion channels it is
      found that the most important effects are associated with energetics rather than
      dynamics. Nevertheless, MD simulations provide what is probably the most
      realistic description of the actual reactive events. The resulting insight is
      crucial in studies of fast photobiological reactions and instructive in cases of
      slower processes.

PMID- 12069624
TI  - Long time dynamics of complex systems.
AB  - Molecular dynamics trajectories of large biological molecules are restricted to
      nanoseconds. We describe a computational method, based on optimization of a
      functional, to extend the time of molecular simulations by orders of magnitude.
      Variants of our technique have already produced microsecond and millisecond
      trajectories. The large steps enable feasible computations of atomically detailed
      approximate trajectories. Numerical examples are provided: (i) a conformational
      change in blocked glycine peptide and (ii) helix formation of an alanine-rich
      peptide.

PMID- 12069625
TI  - Molecular dynamics applied to X-ray structure refinement.
AB  - Simulated annealing, in the form of temperature-controlled molecular dynamics,
      has been successfully applied to macromolecular X-ray structure optimization. The
      theory and practice of the method are reviewed, and some recent improvements are
      described.

PMID- 12069626
TI  - Evolution and physics in comparative protein structure modeling.
AB  - From a physical perspective, the native structure of a protein is a consequence
      of physical forces acting on the protein and solvent atoms during the folding
      process. From a biological perspective, the native structure of proteins is a
      result of evolution over millions of years. Correspondingly, there are two types
      of protein structure prediction methods, de novo prediction and comparative
      modeling. We review comparative protein structure modeling and discuss the
      incorporation of physical considerations into the modeling process. A good
      starting point for achieving this aim is provided by comparative modeling by
      satisfaction of spatial restraints. Incorporation of physical considerations is
      illustrated by an inclusion of solvation effects into the modeling of loops.

PMID- 12069627
TI  - Molecular dynamics simulations of the protein unfolding/folding reaction.
AB  - All-atom molecular dynamics simulations of proteins in solvent are now able to
      realistically map the protein-unfolding pathway. The agreement with experiments
      probing both folding and unfolding suggests that these simulated unfolding events
      also shed light on folding. The simulations have produced detailed models of
      protein folding transition, intermediate, and denatured states that are in both
      qualitative and quantitative agreement with experiment. The various studies
      presented here highlight how such simulations both complement and extend
      experiment.

PMID- 12069628
TI  - Free energy simulations come of age: protein-ligand recognition.
AB  - In recent years, molecular dynamics simulations of biomolecular free energy
      differences have benefited from significant methodological advances and increased
      computer power. Applications to molecular recognition provide an understanding of
      the interactions involved that goes beyond, and is an important complement to,
      experimental studies. Poisson-Boltzmann electrostatic models provide a faster and
      simpler free energy method in cases where electrostatic interactions are
      important. We illustrate both molecular dynamics and Poisson-Boltzmann methods
      with a detailed study of amino acid recognition by aspartyl-tRNA synthetase,
      whose specificity is important for maintaining the integrity of the genetic code.

PMID- 12069629
TI  - Lipid bilayers, NMR relaxation, and computer simulations.
AB  - Brownian and molecular dynamics simulations of a lipid bilayer are described, and
      the calculated frequency-dependent (13)C NMR T(1) relaxation times are compared
      with experiment. A consistent model emerges. Through fast internal motions,
      individual lipids average themselves into relatively cylindrical shapes on the
      100 ps time scale and "wobble" in a cone-like potential on the nanosecond time
      scale. These motions take place in a highly fluid environment, much like a liquid
      alkane. Lateral diffusion of the lipids is on a significantly longer time scale
      because of restrictions at the bilayer/water interface, not because the interior
      of the bilayer is highly viscous.

PMID- 12069631
TI  - The role and perspective of ab initio molecular dynamics in the study of
      biological systems.
AB  - Ab initio molecular dynamics (MD) allows realistic simulations to be performed
      without adjustable parameters. In recent years, the technique has been used on an
      increasing number of applications to biochemical systems. Here we describe the
      principles on which ab initio MD is based. We focus on the most popular
      implementation, based on density functional theory and plane wave basis set. By a
      survey of recent applications, we show that despite the current limitations of
      size and time scale, ab initio MD (and hybrid ab initio MD/MM approaches) can
      play an important role for the modeling of biological systems. Finally, we
      provide a perspective for the advancement of methodological approaches which may
      further expand the scope of ab initio MD in biomolecular modeling.

PMID- 12069630
TI  - Protein and peptide folding explored with molecular simulations.
AB  - Molecular simulations, comprising models with atomic details of polypeptide and
      solvent as well as minimalist models employing only C alpha atoms, are being used
      with specialized simulation methods from statistical mechanics to examine
      fundamental questions in peptide and protein folding mechanism, kinetics, and
      thermodynamics. Detailed calculations of free energy changes along coordinates
      describing the formation of hydrogen-bonding interactions in helical, turn, and
      beta-sheet models provide insights into the time scale and mechanism of secondary
      structure formation. Potential roles for these processes in directing protein
      folding are also elucidated by such calculations. Analogous methodologies
      extended to more complex polypeptides with tertiary structures (proteins) are
      used to explore global questions about protein folding landscapes, to delineate
      atomic details of folding mechanism, and to elucidate putative roles for solvent
      in the late stages of folding.

PMID- 12069632
TI  - Molecular dynamics applied to nucleic acids.
AB  - In this Account, we focus on molecular dynamics (MD) simulations involving fully
      solvated nucleic acids. Historically, MD simulations were first applied to
      proteins and several years later to nucleic acids. The first MD simulations of
      DNA were carried out in vacuo, but nowadays fully solvated systems are common
      practice. Recently, technical improvements have made it possible to conduct
      accurate MD simulations of highly charged nucleic acids. The state-of-the-art of
      MD simulations and a number of applications on various nucleic acid systems are
      discussed.

PMID- 12069633
TI  - Long time dynamic simulations: exploring the folding pathways of an Alzheimer's
      amyloid Abeta-peptide.
AB  - We describe the MaxFlux algorithm for the computation of likely pathways for
      global macromolecular conformational transitions. The algorithm assumes an
      overdamped diffusive dynamics for the biomolecule, appropriate to large scale
      conformational changes. As an application of the MaxFlux method, we explore
      conformational transitions between alpha-helical, collapsed coil, and beta-sheet
      conformations of an amyloid Abeta-peptide. The resulting transition pathways are
      analyzed in terms of the mechanism of conformational transition and the
      progression of the peptide energetics in both an aqueous and a membrane-mimicking
      nonpolar solvent.

PMID- 12069634
TI  - Computer simulation studies of model biological membranes.
AB  - This Account is focused on computer simulation studies of model biological
      membrane systems with potential applications in biomedical research. In the past
      decade, classical molecular dynamics has provided novel insights into the
      properties of model biomembrane systems, including the nature of the DNA-lipid
      interactions, the effect of pore-forming transmembrane peptides on the lipid
      environment, and the partitioning of volatile anesthetic molecules. Such
      simulations, employing full atomic detail, are typically restricted to systems of
      dimensions less than approximately 10 nm. Simplified models of the coarse-grain
      type have been intended to bridge the gap between full atomistic detail and the
      mesoscopic (micron) regime. The use of such models is illustrated with the
      example of anesthetics in a phospholipid bilayer.

PMID- 12069635
TI  - Vitiligo: a manifestation of apoptosis?
AB  - Vitiligo is a common cutaneous disorder that has significant biological and
      social consequences for those affected. It is characterized by a loss of
      melanocytes from the epidermis, which results in the absence of melanin, i.e.
      depigmentation. There are numerous hypotheses about the etiology of vitiligo, but
      no data to definitively prove one theory over another. It is likely that there
      are numerous causes for the loss of these melanocytes. One way to approach the
      identification of the etiology is to determine the mechanism by which the
      melanocytes are destroyed. The two known mechanisms for the destruction of cells
      are necrosis and apoptosis. One purpose of this paper is to review the extant
      data that might suggest which of the two mechanisms is operative against
      melanocytes in patients with vitiligo. The histological data, and some laboratory
      data, support apoptosis, rather than necrosis, as the mechanism for removal of
      melanocytes. Apoptosis can be induced by a variety of factors, including immune
      cytokines, some environmental chemicals (for example substituted hydroquinones
      such as monobenzone) or other molecular mechanisms. Current therapies, such as
      corticosteroids and ultraviolet light, do affect apoptosis in a variety of ways.
      Confirmation of apoptosis as a mechanism, and identification of how apoptosis is
      initiated to produce vitiligo, can serve as a basis for devising medications that
      might stop the progression of the disorder. The problem of vitiligo would be
      essentially solved if there was a medication that is well tolerated in children,
      adults and pregnant women, and that would halt the progression of the
      depigmentation. The study of apoptosis, mechanisms of its induction, and the ways
      to block apoptosis, is one possible way to find both the causes of depigmentation
      and medications to prevent its progression.

PMID- 12069636
TI  - Human herpesvirus 7 in dermatology: what role does it play?
AB  - Human herpesvirus 7 (HHV-7) was discovered in 1989 as a new member of the beta
      herpesvirus subfamily. Primary infection occurs early in life and manifests as
      exanthema subitum, or other febrile illnesses mimicking measles and rubella.
      Thus, HHV-7 has to be considered as a causative agent in a variety of macular
      papular rashes in children. In addition, HHV-7 was found in some cases of other
      inflammatory skin disorders, such as psoriasis. There are controversial data on
      the detection of HHV-7 in pityriasis rosea, but so far there is not enough
      evidence for a pathogenetic association of HHV-7 with this exanthematic skin
      disease. Although HHV-7 can be found in some cases of Hodgkin's disease, there
      are no data supporting a direct causative role in this lymphoma type nor in other
      nodal or primary cutaneous lymphomas. In various epidemiologic forms of Kaposi's
      sarcoma, infection of monocytic cells with HHV-7 was demonstrated, which may
      indirectly influence tumor biology. In the context of immunosuppression, HHV-7
      has recently been identified as an emerging pathogen in transplant recipients and
      may exacerbate graft rejection in renal transplant recipients. The ability of HHV
      7 to induce cytokine production in infected cells could make HHV-7 an important
      pathogenetic co-factor in inflammatory and neoplastic disorders. Moreover, the
      restricted cellular tropism of HHV-7 may render this virus an interesting vector
      for gene therapy. Thirteen years after the discovery of HHV-7, there has been
      considerable progress in characterizing its genetic structure, virus-induced
      effects on infected host cells and in the development of diagnostic tools.
      Nevertheless, the role of HHV-7 in various skin diseases and the clinical
      manifestations of reactivation of HHV-7 infection have still to be defined.

PMID- 12069637
TI  - Self-tanning lotions: are they a healthy way to achieve a tan?
AB  - Self-tanning creams utilize dihydroxyacetone (DHA) as an active agent, to produce
      a temporary staining of the skin. DHA is a 3-carbon sugar that interacts with the
      protein-rich stratum corneum to produce melanoidins, which are brown
      chromophores. Lower concentrations of DHA produce lighter skin-staining, while
      higher concentrations produce darker skin-staining, resulting in the simulation
      of a tan for persons of all skin types. DHA is well tolerated, for both internal
      ingestion and topical application, with the exception of infrequent allergic
      reaction in some patients. However, self-tanning creams only offer a sun
      protection factor (SPF) of 3 to 4, with protection at the low end of the visible
      spectrum and limited ultraviolet A protection. In addition, this SPF is only
      present for several hours after application of the product, and does not last for
      the duration of the tan. Self-tanning creams are a method of safely simulating
      the appearance of a tan without photoprotection. However, other sun protection
      will be required.

PMID- 12069638
TI  - Cutaneous tuberculosis: diagnosis and treatment.
AB  - As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas
      with a high incidence of HIV infection and multi-drug resistant pulmonary
      tuberculosis. Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG
      vaccine cause tuberculosis involving the skin. True cutaneous tuberculosis
      lesions can be acquired either exogenously or endogenously, show a wide spectrum
      of morphology and M. tuberculosis can be diagnosed by acid-fast bacilli (AFB)
      stains, culture or polymerase chain reaction (PCR). These lesions include
      tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma,
      orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and
      most cases of papulonecrotic tuberculid. The tuberculids, like cutaneous
      tuberculosis, show a wide spectrum of morphology but M. tuberculosis is not
      identified by AFB stains, culture or PCR. These lesions include lichen
      scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis,
      most cases of erythema induratum of Bazin and some cases of papulonecrotic
      tuberculid. Diagnosis of cutaneous tuberculosis is challenging and requires the
      correlation of clinical findings with diagnostic testing; in addition to
      traditional AFB smears and cultures, there has been increased utilization of PCR
      because of its rapidity, sensitivity and specificity. Since most cases of
      cutaneous tuberculosis are a manifestation of systemic involvement, and the
      bacillary load in cutaneous tuberculosis is usually less than in pulmonary
      tuberculosis, treatment regimens are similar to that of tuberculosis in general.
      In the immunocompromised, such as an HIV infected patient with disseminated
      miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are
      paramount. Unfortunately, despite even the most aggressive efforts, the prognosis
      in these individuals is poor when multi-drug resistant mycobacterium are present.
      An increased awareness of the re-emergence of cutaneous tuberculosis will allow
      for the proper diagnosis and management of this increasingly common skin
      disorder.

PMID- 12069639
TI  - Adverse cutaneous reactions to antidepressants.
AB  - Antidepressants are among the most widely prescribed medications in the United
      States. Adverse cutaneous drug reactions (ACDRs) associated with drugs are
      common, with possibly higher rates associated with psychotropic medications.
      While the vast majority of ACDRs are benign and easily treated, serious and life-
      threatening ACDRs, such as those associated with antidepressants, do rarely
      occur. ACDRs to antidepressants are diagnosed primarily on the basis of the
      patient's history. A clinician who is aware of these common and potentially
      serious adverse events will help avoid their continuation or recurrence. There
      are certain characteristics that place an individual at higher risk for an ACDR
      such as female gender, increasing age, African-American ethnicity, use of
      multiple medications and presence of a serious illness. If a cutaneous reaction
      occurs in an outpatient setting, it is advisable to discontinue the offending
      antidepressant and substitute it with one from another class. Treatment of the
      ACDR should be symptomatic if the patient shows no other significant signs of
      reaction. If other signs are present, however, a dermatology consultation should
      be obtained. Since the diagnosis of ACDRs is often tentative, and the exanthema
      is likely to be benign, the physician treating a patient with a mood or anxiety
      disorder must weigh the risk of developing these potential problems against the
      possibility of relapse of the psychiatric disorder should the medication be
      discontinued.

PMID- 12069640
TI  - Complementary/alternative medicine in dermatology: evidence-assessed efficacy of
      two diseases and two treatments.
AB  - The objective of this article is to provide a brief, but critical, overview of
      the evidence related to complementary/alternative medicine (CAM) use, and to
      offer valid and useful information for dermatologists in clinical practice.
      Systematic literature searches were conducted on these databases: Medline,
      EMBASE, The Cochrane Library, CISCOM and AMED (until October 2000). Where
      appropriate, the evaluation of the published literature was based on systematic
      reviews and randomized controlled trials. After scanning the literature it was
      decided to focus on a selection of two conditions (atopic dermatitis and chronic
      venous insufficiency) and two treatment modalities (aloe vera gel and tea tree
      oil). Data for the life-time prevalence of CAM use by patients with
      dermatological disease ranges between 35 to 69%. The most popular modalities
      include herablism and (other) dietary supplements, while atopic dermatitis is one
      of the conditions most frequently treated with CAM. For patients with atopic
      dermatitis the evidence relates to autogenic training, hypnotherapy, diet, herbal
      medicine, and dietary supplements. Compelling evidence of effectiveness exists
      for none of these therapies. However, some promising data have been reported for
      those with a psychological component: autogenic training, biofeedback and
      hypnotherapy. For chronic venous insufficiency there is relatively convincing
      evidence for the effectiveness of oral horse chestnut seed extract. The data for
      aloe vera gel and tea tree oil indicate that for neither is there compelling
      evidence of effectiveness. The use of CAM treatments is not free of risk; direct
      and indirect risks associated with CAM must be considered.

PMID- 12069641
TI  - Clindamycin/benzoyl peroxide gel: a review of its use in the management of acne.
AB  - Clindamycin/benzoyl peroxide gel has demonstrated clinical efficacy in the
      treatment of acne vulgaris through both antibacterial and anti-inflammatory
      means. Benzoyl peroxide may exert its antibacterial activity by the interaction
      of oxidized intermediates with elements of bacterial cells. Clindamycin inhibits
      bacterial protein synthesis by binding to the 50S ribosomal subunits causing
      inhibition of peptide-bond formation. Benzoyl peroxide decreases inflammatory
      damage by inhibiting the release of reactive oxygen species from
      polymorphonuclear leukocytes (PMNs) through the killing of PMNs. Clindamycin
      suppresses the complement-derived chemotaxis of polymorphonuclear leukocytes in
      vitro, thereby reducing the potential for inflammation. Several well designed
      clinical trials have demonstrated that twice-daily application of clindamycin
      1%/benzoyl peroxide 5% gel for 10 to 16 weeks was more effective in reducing the
      number of inflammatory lesions than benzoyl peroxide 5%, clindamycin 1% or
      vehicle in patients with mild to moderately severe acne. Two studies also showed
      clindamycin/benzoyl peroxide to be more effective than benzoyl peroxide,
      clindamycin or vehicle in reducing total lesions, and one study showed
      clindamycin/benzoyl peroxide to be significantly more efficacious than
      clindamycin or vehicle in reducing the number of noninflammatory lesions.
      Moreover, in two trials, physician-rated mean global improvement scores, as well
      as patient-rated scores in one of those trials, were significantly greater in the
      clindamycin/benzoyl peroxide group than in the benzoyl peroxide, clindamycin or
      vehicle groups. In another study, clindamycin/benzoyl peroxide was as efficacious
      as benzoyl peroxide/erythromycin in the reduction of inflammatory and
      noninflammatory lesions and in raising mean global improvement scores, but was
      significantly more effective than benzoyl peroxide in the reduction of
      inflammatory lesions and in increasing both physician- and patient-assessed
      global improvement scores. Clindamycin/benzoyl peroxide gel applied twice daily
      was well tolerated in clinical trials in patients with acne, and has a
      tolerability profile similar to that of benzoyl peroxide alone. The most common
      adverse events were dry skin, peeling, erythema and rash; however, adverse event
      caused treatment discontinuation rates for patients using clindamycin/benzoyl
      peroxide were low, ranging from 0 to 0.8%. CONCLUSIONS: Clindamycin/benzoyl
      peroxide gel has demonstrated efficacy and good overall tolerability in several
      well designed clinical studies in the topical treatment of patients with mild to
      moderately severe acne vulgaris. Clindamycin/benzoyl peroxide was more effective
      than benzoyl peroxide, clindamycin or vehicle, and similar in efficacy to benzoyl
      peroxide/erythromycin in the reduction of inflammatory lesions and in raising
      physician- and patient-assessed mean global improvement scores. It may be useful
      in treating patients with acne caused by resistant strains of Propionibacterium
      acnes. Clindamycin/benzoyl peroxide gel is an effective topical agent in the
      treatment of patients with mild to moderately severe acne. It is a suitable
      alternative for patients who are currently using topical antibacterials either
      alone or in conjunction with other topical anti-acne agents or systemic
      antibacterials.

PMID- 12069642
TI  - Cutaneous drug reaction case reports: from the world literature.

PMID- 12069643
TI  - Guided visual search in individuals with mental retardation.
AB  - The ability of individuals with mental retardation to focus on task-relevant
      elements of complex visual arrays and increase visual-search efficiency was
      investigated. Initial assessments of visual-search efficiency were conducted to
      identify pairs of features for the form and size dimensions for which each
      participant demonstrated serial search. Subsequently, color was added as a
      defining feature that could guide search to a subset of the elements in the
      array. Results indicated that all of the individuals with mental retardation were
      able to limit attention to the task-relevant items on the guided search task,
      thus greatly reducing overall target identification times. Results show that
      individuals with mental retardation can demonstrate sophisticated visual
      selective attention skills when visual arrays are structured appropriately.

PMID- 12069644
TI  - Mediators' emotional responses to self-injurious behavior: an experimental study.
AB  - Researchers have suggested that mediators find challenging behaviors aversive. An
      ecologically valid control comparison study to support this contention was
      conducted. Sixty mediators from schools for children with mental retardation
      watched one of five carefully matched videos depicting no self-injury, self
      injury maintained by positive reinforcement, self-injury maintained by negative
      reinforcement, and self-injury unrelated to social events. Those viewing the no
      self-injury video reported fewer negative emotional responses than did those
      watching self-injury videos. Effects of behavioral function were found on
      mediators' self-reported emotional responses. In particular, self-injury
      maintained by negative reinforcement was associated with more self-reported
      negative emotion. Methodological issues and implications for research and
      practice are discussed.

PMID- 12069645
TI  - Effects of risperidone on aberrant behavior in persons with developmental
      disabilities: II. Social validity measures.
AB  - Consumer satisfaction and social validity were measured during a double-blind,
      placebo-controlled evaluation of the atypical neuroleptic risperidone in treating
      severe aberrant behavior of persons with developmental disabilities. First, a
      satisfaction survey was completed after a medication trial by each participant's
      caregiver. Results showed that 100% of the caregivers felt that participation was
      a positive experience for themselves and participants. Second, 52 community
      members viewed videotapes of 5 participants during a clinical interview when they
      were taking either placebo or risperidone. Raters also indicated that when on the
      medication, participants displayed fewer aberrant behaviors, were less irritable,
      in a better mood, and were more responsive to their environment.

PMID- 12069647
TI  - Prevalence of hepatitis virus infections in an institution for persons with
      developmental disabilities.
AB  - In 1994-1995, we collected medical and serologic data on viral hepatitis
      infection on 1,235 residents of Sonoma Developmental Center. Residents were
      mostly White and had lived in the Center over 10 years. Only 3 residents (.3%)
      had hepatitis C virus infection, and 633 (60.2%) had past or current hepatitis B
      virus infection. The prevalence of hepatitis B virus infection rose rapidly with
      longer residence in institutions. Past hepatitis A virus infection had occurred
      in 494 residents (42.1%). The rise in its prevalence with duration of residence
      was much less than that seen with hepatitis B virus infection. Although hepatitis
      C virus infection was relatively rare at the Center, many residents had past
      hepatitis A and hepatitis B virus infections.

PMID- 12069646
TI  - Onset of dyskinesia and changes in postural task performance during the course of
      neuroleptic withdrawal.
AB  - The effect of neuroleptic withdrawal on postural task performance of 20 adults
      with mental retardation was examined. Dyskinesia was measured using the DISCUS
      rating scale and postural stability using a force platform during a prospective
      longitudinal neuroleptic medication withdrawal protocol. Assessments were
      conducted at baseline and monthly intervals, extending to approximately one year
      following complete medication withdrawal, when significant changes in amount of
      postural motion and sequential pattern of postural movement complexity were
      observed. Postural task performance tended to return to near baseline levels at
      periods of up to 1 year following medication withdrawal, although one third of
      the subjects continued to display atypical postural motion profiles at follow-up.
      Results provide within-subject evidence that tardive dyskinesia is associated
      with generalized changes in motor control and not simply peripheral disturbances
      of movement.

PMID- 12069648
TI  - Multicomponent procedure to teach conditional discriminations to children with
      autism.
AB  - Five children with autism with a history of failing to acquire conditional
      discriminations learned to discriminate objects in response to spoken names or to
      match amounts to numbers with a combined blocking procedure. The procedure for
      teaching object discriminations involved (a) presenting the same spoken word
      until 10 consecutive correct responses occurred and (b) keeping the left-right
      location of the objects on the table constant. After mastery, the requirement for
      changing the spoken word was gradually reduced. Finally, the spoken words were
      presented randomly. In the final stage, the objects were located randomly. The
      procedure to teach number matching was similar. All children learned these
      discriminations with few errors. This procedure may be beneficial in teaching
      conditional discriminations to children with learning difficulties.

PMID- 12069649
TI  - Longitudinal study on the adaptive and challenging behaviors of
      deinstitutionalized adults with mental retardation.
AB  - Adaptive and challenging behavior changes associated with movement from
      Minnesota's state institutions to community homes were examined. Most of the 148
      participants who moved had severe or profound mental retardation, significant
      challenging behavior, and several decades of institutionalization. Adaptive and
      challenging behavior were assessed in the institution and thereafter annually in
      the community. Relative to institutional levels, adaptive behavior declined among
      residents who moved to community ICFs/MR but was unchanged for the HCBS Waiver
      group. Challenging behavior tended to worsen initially but, except for
      internalized behavior, no longer differed from institutional levels by the second
      community assessment. Change in challenging behavior was unrelated to community
      residence type. Previous papers involving these participants showed consistent
      lifestyle enhancements and reduced service costs relative to the institution.

PMID- 12069651
TI  - A piece of my mind. First morning back.

PMID- 12069652
TI  - Cancer studies explore targeted therapy, researchers seek new prevention
      strategies.

PMID- 12069653
TI  - Pain guidelines encourage vigilance.

PMID- 12069658
TI  - Cognitive outcomes following cardiopulmonary bypass.

PMID- 12069659
TI  - Cognitive outcomes following cardiopulmonary bypass.

PMID- 12069660
TI  - Cognitive outcomes following cardiopulmonary bypass.

PMID- 12069661
TI  - Cognitive outcomes following cardiopulmonary bypass.

PMID- 12069663
TI  - When should perioperative beta-blockers be discontinued?

PMID- 12069665
TI  - Emergency treatment for commotio cordis.

PMID- 12069667
TI  - Alpha-methylacyl coenzyme A racemase as a marker for prostate cancer.

PMID- 12069669
TI  - Plasma lysophosphatidic acid concentration and ovarian cancer.

PMID- 12069670
TI  - Cranberry juice and adhesion of antibiotic-resistant uropathogens.

PMID- 12069671
TI  - Early statin initiation and outcomes in patients with acute coronary syndromes.
AB  - CONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly
      demonstrated; however, the role of early initiation of statins after acute
      coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of
      early statin initiation (< or = 7 days) after ACS with 90-day and 1-year
      outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical
      trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical
      centers in 37 countries. PATIENTS: A total of 12,365 ACS patients randomized from
      August 1997 to August 1999 who were not taking statins prior to the index ACS and
      who either started statin therapy early (median, 2.0 [interquartile range, 1.0
      3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never
      received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence
      of death; death or myocardial infarction (MI); and death, MI, or severe recurrent
      ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year
      unadjusted mortality comparison suggested early statin benefit (1.2% for early
      statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval
      [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no
      statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit
      was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or
      death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92
      1.18). After propensity and covariate adjustment, there were no 90-day or 1-year
      differences between the early-statin group and the no-statin group. The 90-day
      adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95%
      CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI,
      0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among
      2711 patients with core laboratory lipid analysis, early statin was associated
      with higher adjusted risk for death or death or MI at cholesterol levels below
      treatment guidelines but was more favorable at higher levels. CONCLUSIONS: In
      this study, there was no relationship between early initiation of statin therapy
      and improved outcomes although our subset analysis suggests that outcomes after
      early statin initiation may vary with cholesterol levels. Confirmation of early
      treatment effects of statins on outcomes awaits the results of adequately powered
      randomized clinical trials.

PMID- 12069672
TI  - Trends in antimicrobial prescribing rates for children and adolescents.
AB  - CONTEXT: Annual rates of antimicrobial prescribing for children by office-based
      physicians increased from 1980 through 1992. The development of antimicrobial
      resistance, which increased for many organisms during the 1990s, is associated
      with antimicrobial use. To combat development of antimicrobial resistance,
      professional and public health organizations undertook efforts to promote
      appropriate antimicrobial prescribing. OBJECTIVE: To assess changes in
      antimicrobial prescribing rates overall and for respiratory tract infections for
      children and adolescents younger than 15 years. DESIGN, SETTING, AND
      PARTICIPANTS: National Ambulatory Medical Care Survey data provided by 2500 to
      3500 office-based physicians for 6500 to 13 600 pediatric visits during 2-year
      periods from 1989-1990 through 1999-2000. MAIN OUTCOME MEASURES: Population- and
      visit-based antimicrobial prescribing rates overall and for respiratory tract
      infections (otitis media, pharyngitis, bronchitis, sinusitis, and upper
      respiratory tract infection) among children and adolescents younger than 15
      years. RESULTS: The average population-based annual rate of overall antimicrobial
      prescriptions per 1000 children and adolescents younger than 15 years decreased
      from 838 (95% confidence interval [CI], 711-966) in 1989-1990 to 503 (95% CI, 419
      588) in 1999-2000 (P for slope <.001). The visit-based rate decreased from 330
      antimicrobial prescriptions per 1000 office visits (95% CI, 305-355) to 234 (95%
      CI, 210-257; P for slope <.001). For the 5 respiratory tract infections, the
      population-based prescribing rate decreased from 674 (95% CI, 568-781) to 379
      (95% CI, 311-447; P for slope <.001) and the visit-based prescribing rate
      decreased from 715 (95% CI, 682-748) to 613 (95% CI, 570-657; P for slope <.001).
      Both population- and visit-based prescribing rates decreased for pharyngitis and
      upper respiratory tract infection; however, for otitis media and bronchitis,
      declines were only observed in the population-based rate. Prescribing rates for
      sinusitis remained stable. CONCLUSION: The rate of antimicrobial prescribing
      overall and for respiratory tract infections by office-based physicians for
      children and adolescents younger than 15 years decreased significantly between
      1989-1990 and 1999-2000.

PMID- 12069673
TI  - Changes in antibiotic prescribing for children after a community-wide campaign.
AB  - CONTEXT: Overuse of antibiotics has contributed to microbial resistance,
      compromising the treatment of bacterial infections. Very high levels (>50%) of
      antibiotic resistance among invasive Streptococcus pneumoniae have been
      documented in Knox County, Tennessee. OBJECTIVE: To determine the effectiveness
      of a community-wide intervention aimed at reducing inappropriate antibiotic use
      among children. DESIGN, SETTING, AND PARTICIPANTS: The Knox County Health
      Department led a multifaceted year-long campaign (May 1997 through April 1998)
      aimed at decreasing unnecessary antibiotic use among children. Tennessee's 3
      other major urban counties (Shelby, Hamilton, and Davidson) did not conduct
      similar campaigns and served as controls. Evaluation included white and black
      children (aged <15 years) enrolled in Tennessee's Medicaid Managed Care Program
      in the 4 study counties, representing 36% of the study counties' children (464
      200 person-years observed). INTERVENTION: Educational efforts were directed
      toward health care practitioners (primarily via peer leader presentations) and to
      the parents of young children and the public (primarily via printed materials).
      MAIN OUTCOME MEASURE: The intervention-attributable effect on antibiotic use,
      defined as the excess percentage change in oral antibiotic prescription rates in
      Knox County between the 12-month preintervention and postintervention periods,
      relative to that of control counties. RESULTS: Antibiotic prescription rates
      declined 19% and 8% among Knox County and control county children, respectively,
      yielding an 11% intervention-attributable decline (95% confidence interval, 8%
      14%; P<.001). The intervention-attributable decrease in prescription rates was
      greatest among children aged 1 to less than 5 years (among white children, 8%
      [P<.001]; among black children, 18% [P<.001]). CONCLUSIONS: A community-wide
      educational intervention reduced antibiotic prescription levels among children in
      Knox County.

PMID- 12069674
TI  - Vasectomy and risk of prostate cancer.
AB  - CONTEXT: Vasectomy is a common method of contraception, but concern exists about
      a reported association with risk of prostate cancer. OBJECTIVE: To examine
      whether vasectomy increases risk of prostate cancer. DESIGN, SETTING, AND
      PARTICIPANTS: National population-based case-control study of 923 new cases of
      prostate cancer among men aged 40 to 74 years from the New Zealand Cancer
      Registry who were on the general electoral roll. Controls (n = 1224) were
      randomly selected from the general electoral roll, with frequency matching to
      cases in 5-year age groups. Cases (3-15 months after diagnosis) and controls were
      interviewed by telephone between January 1997 and November 1999. MAIN OUTCOME
      MEASURES: Relative risk (RR) of prostate cancer for men who had had a vasectomy
      vs those who had not. RESULTS: There was no association between prostate cancer
      and vasectomy (RR, 0.92; 95% confidence interval [CI], 0.75-1.14) nor with time
      since vasectomy (RR, 0.92; 95% CI, 0.68-1.23 for > or = 25 years since
      vasectomy). Adjustment for social class, geographic region, religious
      affiliation, and a family history of prostate cancer did not affect these RRs.
      CONCLUSIONS: Vasectomy does not increase the risk of prostate cancer, even after
      25 years or more.

PMID- 12069675
TI  - Vitamins for chronic disease prevention in adults: scientific review.
AB  - CONTEXT: Although vitamin deficiency is encountered infrequently in developed
      countries, inadequate intake of several vitamins is associated with chronic
      disease. OBJECTIVE: To review the clinically important vitamins with regard to
      their biological effects, food sources, deficiency syndromes, potential for
      toxicity, and relationship to chronic disease. DATA SOURCES AND STUDY SELECTION:
      We searched MEDLINE for English-language articles about vitamins in relation to
      chronic diseases and their references published from 1966 through January 11,
      2002. DATA EXTRACTION: We reviewed articles jointly for the most clinically
      important information, emphasizing randomized trials where available. DATA
      SYNTHESIS: Our review of 9 vitamins showed that elderly people, vegans, alcohol
      dependent individuals, and patients with malabsorption are at higher risk of
      inadequate intake or absorption of several vitamins. Excessive doses of vitamin A
      during early pregnancy and fat-soluble vitamins taken anytime may result in
      adverse outcomes. Inadequate folate status is associated with neural tube defect
      and some cancers. Folate and vitamins B(6) and B(12) are required for
      homocysteine metabolism and are associated with coronary heart disease risk.
      Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is
      associated with decreased occurrence of fractures when taken with calcium.
      CONCLUSIONS: Some groups of patients are at higher risk for vitamin deficiency
      and suboptimal vitamin status. Many physicians may be unaware of common food
      sources of vitamins or unsure which vitamins they should recommend for their
      patients. Vitamin excess is possible with supplementation, particularly for fat
      soluble vitamins. Inadequate intake of several vitamins has been linked to
      chronic diseases, including coronary heart disease, cancer, and osteoporosis

PMID- 12069676
TI  - Vitamins for chronic disease prevention in adults: clinical applications.
AB  - Vitamin deficiency syndromes such as scurvy and beriberi are uncommon in Western
      societies. However, suboptimal intake of some vitamins, above levels causing
      classic vitamin deficiency, is a risk factor for chronic diseases and common in
      the general population, especially the elderly. Suboptimal folic acid levels,
      along with suboptimal levels of vitamins B(6) and B(12), are a risk factor for
      cardiovascular disease, neural tube defects, and colon and breast cancer; low
      levels of vitamin D contribute to osteopenia and fractures; and low levels of the
      antioxidant vitamins (vitamins A, E, and C) may increase risk for several chronic
      diseases. Most people do not consume an optimal amount of all vitamins by diet
      alone. Pending strong evidence of effectiveness from randomized trials, it
      appears prudent for all adults to take vitamin supplements. The evidence base for
      tailoring the contents of multivitamins to specific characteristics of patients
      such as age, sex, and physical activity and for testing vitamin levels to guide
      specific supplementation practices is limited. Physicians should make specific
      efforts to learn about their patients' use of vitamins to ensure that they are
      taking vitamins they should, such as folate supplementation for women in the
      childbearing years, and avoiding dangerous practices such as high doses of
      vitamin A during pregnancy or massive doses of fat-soluble vitamins at any age.

PMID- 12069677
TI  - Estimating treatment effects from observational data: dissonant and resonant
      notes from the SYMPHONY trials.

PMID- 12069678
TI  - Dynamics of antibiotic prescribing for children.

PMID- 12069679
TI  - News media coverage of screening mammography for women in their 40s and tamoxifen
      for primary prevention of breast cancer.
AB  - CONTEXT: In the late 1990s, 3 events pertaining to breast cancer prevention
      received considerable attention in the US news media: a National Institutes of
      Health (NIH) consensus panel recommended against routine screening mammography
      for women in their 40s (January 1997), the National Cancer Institute (NCI)
      subsequently reversed the recommendation (March 1997), and an NCI-sponsored study
      demonstrated the efficacy of tamoxifen in the primary prevention of breast cancer
      (April 1998). OBJECTIVE: To examine how the major US news media covered the
      potential benefits and harms of 2 breast cancer preventive strategies. DESIGN AND
      SETTING: Content analysis of US news stories reporting on the breast cancer
      prevention events. We used Lexis-Nexis to search for print news stories in the 10
      highest-circulation US newspapers and requested transcripts from 3 major
      television networks to obtain all relevant news coverage in the 2 weeks following
      each event. MAIN OUTCOME MEASURES: Attitude toward preventive strategy
      (encourage, neutral, discourage); level of uncertainty about benefit and how
      benefits and harms were presented. RESULTS: Twenty-seven stories about the NIH
      consensus panel, 24 about the NCI reversal, and 34 about tamoxifen appeared in
      high-profile news media within 2 weeks of each event. Sixty-seven percent of NIH
      consensus panel stories left the impression that there was a lot of uncertainty
      about whether women aged 40 to 49 years should undergo screening, but 59%
      suggested that women should probably or definitely be screened. Only 4 stories
      suggested that women faced a genuine decision about what to do. The level of
      uncertainty reported was substantially lower following the NCI reversal (21%
      suggested a lot of uncertainty), and most stories (96%) suggested that women
      should be screened. In contrast, tamoxifen stories highlighted uncertainty about
      what women at high risk should do (62% suggested there was a lot of uncertainty),
      and none left the impression that women should definitely take the drug (24%
      suggested they probably should). Sixty-five percent of these stories suggested
      that women faced a genuine choice and would have to weigh the risks and benefits
      themselves. CONCLUSIONS: Most news stories favored routine use of screening
      mammography and urged caution about using tamoxifen. Almost all noted the
      potential harms of each preventive strategy; however, the negative aspects of
      tamoxifen received greater emphasis. Whereas taking tamoxifen was presented as a
      difficult decision, having a mammogram was presented as something women ought to
      do.

PMID- 12069680
TI  - Variation of mood and empathy during internship.
AB  - CONTEXT: Internship is a time of great transition, during which mood disturbances
      are common. However, variations in mood and empathy levels throughout the
      internship year have not been investigated. OBJECTIVE: To examine mood patterns
      and changes in empathy among internal medicine residents over the course of the
      internship year. DESIGN: Cohort study of interns involving completion of survey
      instruments at 4 points: time 1 (June 2000; Profile of Mood States [POMS] and
      Interpersonal Reactivity Index [IRI]), times 2 and 3 (November 2000 and February
      2001; POMS), and time 4 (June 2001; POMS and IRI). SETTING: Internal medicine
      residency program at a university-based medical center. PARTICIPANTS: Sixty-one
      interns. MAIN OUTCOME MEASURES: Baseline scores of mood states and empathy;
      trends in mood states and empathy over the internship year. RESULTS: Response
      rates for time 1 were 98%; for time 2, 72%; for time 3, 79%; and for time 4, 79%.
      Results of the POMS revealed that physicians starting their internship exhibit
      less tension, depression, anger, fatigue, and confusion and have more vigor than
      general adult and college student populations (P<.001 for all). Results of the
      IRI showed better baseline scores for perspective taking (P<.001) and empathic
      concern (P =.007) and lower scores for personal distress (P<.001) among interns
      compared with norms. Five months into internship, however, POMS scores revealed
      significant increases in the depression-dejection (P<.001), anger-hostility
      (P<.001), and fatigue-inertia (P<.001) scales, as well as an increase in IRI
      personal distress level (P<.001). These increases corresponded with decreases in
      the POMS vigor-activity scores (P<.001) and IRI empathic concern measures (P
      =.005). Changes persisted throughout the internship period. CONCLUSIONS: We found
      that, in this sample, enthusiasm at the beginning of internship soon gave way to
      depression, anger, and fatigue. Future research should be aimed at determining
      whether these changes persist beyond internship.

PMID- 12069685
TI  - Lipid modification of proteins in Archaea: attachment of a mevalonic acid-based
      lipid moiety to the surface-layer glycoprotein of Haloferax volcanii follows
      protein translocation.
AB  - Once the newly synthesized surface (S)-layer glycoprotein of the halophilic
      archaeaon Haloferax volcanii has traversed the plasma membrane, the protein
      undergoes a membrane-related, Mg(2+)-dependent maturation event, revealed as an
      increase in the apparent molecular mass and hydrophobicity of the protein. To
      test whether lipid modification of the S-layer glycoprotein could explain these
      observations, H. volcanii cells were incubated with a radiolabelled precursor of
      isoprene, [(3)H]mevalonic acid. In Archaea, isoprenoids serve as the major
      hydrophobic component of archaeal membrane lipids and have been shown to modify
      other haloarchaeal S-layer glycoproteins, although little is known of the
      mechanism, site or purpose of such modification. In the present study we report
      that the H. volcanii S-layer glycoprotein is modified by a derivative of
      mevalonic acid and that maturation of the protein was prevented upon treatment
      with mevinolin (lovastatin), an inhibitor of mevalonic acid biosynthesis. These
      findings suggest that lipid modification of S-layer glycoproteins is a general
      property of halophilic archaea and, like S-layer glycoprotein glycosylation,
      lipid-modification of the S-layer glycoproteins takes place on the external cell
      surface, i.e. following protein translocation across the membrane.

PMID- 12069686
TI  - Irreversible inhibition of the bacterial cysteine protease-transpeptidase sortase
      (SrtA) by substrate-derived affinity labels.
AB  - We report on the first synthesis, kinetic evaluation and application of novel
      substrate-derived inhibitors against the Staphylococcus aureus cysteine protease
      transpeptidase, sortase (staphylococcal surface protein sorting A, SrtA). The
      peptidyl-diazomethane and peptidyl-chloromethane analogues, Cbz
      (benzyloxycarbonyl)-Leu-Pro-Ala-Thr-CHN(2) (I) and Cbz-Leu-Pro-Ala-Thr-CH(2)Cl
      (II) respectively were found to act as time-dependent irreversible inhibitors of
      recombinant sortase (SrtA(DeltaN)). The peptidyl-chloromethane analogue (II) was
      the most powerful with an inhibitor specificity constant (k(i)/K(i)) of 5.3x10(4)
      M(-1).min(-1), approx. 2-fold greater than that determined for the peptidyl
      diazomethane (I). Additionally, using Western-blot analysis, we have been able to
      demonstrate that a biotinylated version of the peptidyl-diazomethane analogue,
      biotin-Ahx (aminohexanoyl)-Leu-Pro-Ala-Thr-CHN(2) (III), can be used as an
      affinity label to detect the presence of wild-type SrtA in crude cell lysates
      prepared from S. aureus.

PMID- 12069688
TI  - Cell-cycle arrest by PD184352 requires inhibition of extracellular signal
      regulated kinases (ERK) 1/2 but not ERK5/BMK1.
AB  - Serum and growth factors activate both the canonical extracellular signal
      regulated kinase (ERK) 1/2 pathway and the ERK5/big mitogen-activated protein
      kinase 1 (BMK) 1 pathway. Pharmacological inhibition of the ERK1/2 pathway using
      PD98059 and U0126 prevents cyclin D1 expression and inhibits cell proliferation,
      arguing that the ERK1/2 pathway is rate limiting for cell-cycle re-entry.
      However, both PD98059 and U0126 also inhibit the ERK5/BMK1 pathway, raising the
      possibility that the anti-proliferative effect of such drugs may be due to
      inhibition of ERK5 or both pathways. Here we characterize the effect of the novel
      mitogen-activated protein kinase/ERK kinase (MEK) inhibitor, PD184352, on the
      ERK1/2 and ERK5 pathways in the Chinese hamster fibroblast cell line CCl39. In
      quiescent cells, serum-stimulated ERK1 activity was completely inhibited by
      PD184352 with an IC50 below 1 microM, whereas ERK5 activation was unaffected even
      at 20 microM. Serum-stimulated DNA synthesis and cyclin D1 expression was
      inhibited by low doses of PD184352, which abolished ERK1 activity but had no
      effect on ERK5. Similarly, in cycling cells PD184352 caused a dose-dependent G1
      arrest and inhibition of cyclin D1 expression at low doses, which inhibited ERK1
      but were without effect on ERK5. These results indicate that the anti
      proliferative effect of PD184352 is due to inhibition of the classical ERK1/2
      pathway and does not require inhibition of the ERK5 pathway.

PMID- 12069687
TI  - Inhibition of peroxisome proliferator-activated receptor (PPAR)-mediated
      keratinocyte differentiation by lipoxygenase inhibitors.
AB  - Lipoxygenase (LOX) metabolites from arachidonic acid and linoleic acid have been
      implicated in atherosclerosis, inflammation, keratinocyte differentiation and
      tumour progression. We previously showed that peroxisome proliferator-activated
      receptors (PPARs) play a role in keratinocyte differentiation and that the
      PPARalpha ligand 8S-hydroxyeicosatetraenoic acid is important in this process. We
      hypothesized that blocking LOX activity would block PPAR-mediated keratinocyte
      differentiation. Three LOX inhibitors, nordihydroguaiaretic acid, quercetin and
      morin, were studied for their effects on primary keratinocyte differentiation and
      PPAR activity. All three LOX inhibitors blocked calcium-induced expression of the
      differentiation marker keratin 1. In addition, activity of a PPAR-responsive
      element was inhibited in the presence of all three inhibitors, and this effect
      was mediated primarily through PPARalpha and PPARgamma. LOX inhibitors decreased
      the activity of a chimaeric PPAR-Gal4-ligand-binding domain reporter system and
      this effect was reversed by addition of PPAR ligands. Ligand-binding studies
      revealed that the LOX inhibitors bind directly to PPARs and demonstrate a novel
      mechanism for these inhibitors in altering PPAR-mediated gene expression.

PMID- 12069689
TI  - Cloning and expression of a novel Mu class murine glutathione transferase
      isoenzyme.
AB  - The present study describes the cDNA cloning, expression and characterization of
      a novel Mu class murine glutathione transferase (GST) isoenzyme. Screening of a
      cDNA library from the small intestine of a female A/J mouse using consensus
      probes derived from Mu class murine GST genes (mGSTM1-mGSTM5) resulted in the
      isolation of a full-length cDNA clone of a previously unknown Mu class GST gene
      (designated as mGSTM7). The choice of tissue was based on our previous
      identification in female A/J mouse small intestine of a potentially novel Mu
      class GST isoenzyme. The deduced amino acid sequence of mGSTM7, which comprises
      of 218 amino acid residues, exhibited about 67-78% identity with other Mu class
      murine GSTs. Recombinant mGSTM7-7 cross-reacted with anti-(GST Mu) antibodies,
      but not with anti-(GST Alpha) or anti-(GST Pi) antibodies. The pI and the reverse
      phase-HPLC elution profile of recombinant mGSTM7-7 were different from those of
      other Mu class murine GSTs. The substrate specificity of mGSTM7-7 was also
      different compared with other Mu class murine GSTs. Interestingly, mGSTM7 had a
      higher identity with the human Mu class isoenzyme hGSTM4 (87% identity and 94%
      similarity in the amino acid sequence) than with any of the known mouse Mu class
      GSTs. Specific activities of recombinant mGSTM7-7 and human GSTM4-4 were
      comparable towards several substrates. For example, similar to hGSTM4-4,
      recombinant mGSTM7-7 was poorly active in catalysing the GSH conjugation of 1
      chloro-2,4-dinitrobenzene and ethacrynic acid, and lacked activity towards 1,2
      dichloro-4-nitrobenzene and 1,2-epoxy-3-(p-nitrophenoxy)propane. These results
      suggested that hGSTM4-4 might be the human counterpart of mouse GSTM7-7. Reverse
      transcription-PCR analysis using mGSTM7-specific primers revealed that mGSTM7 is
      widely expressed in tissues of female A/J mice, including liver, forestomach,
      lung, kidney, colon and spleen.

PMID- 12069691
TI  - Possible attenuation of the G2 DNA damage cell cycle checkpoint in HeLa cells by
      extremely low frequency (ELF) electromagnetic fields.
AB  - BACKGROUND: The issue remains unresolved as to whether low frequency magnetic
      fields can affect cell behaviour, with the possibility that they may be in part
      responsible for the increased incidence of leukaemia in parts of the population
      exposed to them. METHODS: Combined treatment of HeLa cells with gamma-irradiation
      (1, 3 and 5 Grays) and extra low frequency magnetic fields of ~50 Hz was carried
      out under rigorously controlled conditions. RESULTS: Synchronised cells
      progressing from S-phase arrived at mitosis on average marginally ahead of
      irradiation controls not exposed to ELF. In no instance out of a total of twenty
      separate experiments did this "double-insult" further delay entry of cells into
      mitosis, as had been anticipated. CONCLUSION: This apparently "non-genotoxic"
      agent (ELF) appears to be capable of affecting cells that would normally arrest
      for longer in G2, suggesting a weakening of the stringency of the late cycle (G2)
      checkpoint.

PMID- 12069690
TI  - The human DnaJ homologue (Hdj)-1/heat-shock protein (Hsp) 40 co-chaperone is
      required for the in vivo stabilization of the cystic fibrosis transmembrane
      conductance regulator by Hsp70.
AB  - The CFTR (cystic fibrosis transmembrane conductance regulator) gene, defective in
      cystic fibrosis, codes for a polytopic apical membrane protein functioning as a
      chloride channel. Wild-type (wt) CFTR matures inefficiently and CFTR with a
      deletion of Phe-508 (F508del), the most frequent mutation, is substantially
      retained as a core-glycosylated intermediate in the endoplasmic reticulum (ER),
      probably due to misfolding that is recognized by the cellular quality control
      machinery involving molecular chaperones. Here, we overexpressed the heat-shock
      protein (Hsp) 70 chaperone in vivo and observed no changes in degradation rate of
      the core-glycosylated form, nor in the efficiency of its conversion into the
      fully glycosylated form, for either wt- or F508del-CFTR, contrary to previous in
      vitro studies on the affect of heat-shock cognate (Hsc) 70 on part of the first
      nucleotide-binding domain of CFTR. Co-transfection of Hsp70 with its co-chaperone
      human DnaJ homologue (Hdj)-1/Hsp40, however, stabilizes the immature form of wt
      CFTR, but not of F508del-CFTR, suggesting that these chaperones act on a wt
      specific conformation. As the efficiency of conversion into the fully
      glycosylated form is not increased under Hsp70/Hdj-1 overexpression, the lack of
      these two chaperones does not seem to be critical for CFTR maturation and ER
      retention. The effects of 4-phenylbutyrate and deoxyspergualin, described
      previously to interfere with Hsp70 binding, were also tested upon CFTR
      degradation and processing. The sole effect observed was destabilization of
      F508del-CFTR.

PMID- 12069693
TI  - Androgen and retinoic acid interaction in LNCaP cells, effects on cell
      proliferation and expression of retinoic acid receptors and epidermal growth
      factor receptor.
AB  - BACKGROUND: Modulation of the expression of retinoic acid receptors (RAR) alpha
      and gamma in adult rat prostate by testosterone (T) suggests that RAR signaling
      events might mediate some of the androgen effects on prostate cells. METHOD: In
      this study, we examined the interactions between T and retinoic acid (RA) in cell
      growth of human prostate carcinoma cells, LNCaP, and their relationship with the
      expression of RAR and epidermal growth factor receptor (EGF-R). RESULTS: Both T
      and RA, when administered alone, stimulated 3H-thymidine incorporation in LNCaP
      cells in a dose-dependent manner; the effect of each agent was reciprocally
      attenuated by the other agent. Testosterone treatment of LNCaP cells also
      resulted in dose dependent, biphasic increases in RAR alpha and gamma mRNAs;
      increases paralleled that of 3H-thymidine incorporation and were attenuated by
      the presence of 100 nM RA. These results suggest a link between RAR signaling and
      the effect of T on LNCaP cell growth. Gel electrophoretic mobility shift assays
      revealed the presence of putative androgen responsive element (ARE) in the
      promoter region of RAR alpha gene, suggesting that a direct AR-DNA interaction
      might mediate the effects of T on RAR alpha gene. Furthermore, treatment of LNCaP
      cells with 20 nM T resulted in an increase in EGF-R. In contrast, EGF-R was
      suppressed by 100 nM RA that also suppressed the effect of T. CONCLUSIONS:
      Current results demonstrate interactions between T and RA in the expression of
      RARs and cell growth in LNCaP cells. The presence of putative ARE in the promoter
      of the RAR alpha gene suggests that AR-DNA interaction might mediate the effects
      of T on RAR alpha gene. The opposite effects of T and RA on the expression of RAR
      and EGF-R suggest that signal events of these receptors might be involved in the
      interaction between T and RA in the control of LNCaP cell growth.

PMID- 12069694
TI  - Kinetics of maternal immunity against rabies in fox cubs (Vulpes vulpes).
AB  - BACKGROUND: In previous experiments, it was demonstrated that maternal antibodies
      (maAb) against rabies in foxes (Vulpes vulpes) were transferred from the vixen to
      her offspring. However, data was lacking from cubs during the first three weeks
      post partum. Therefore, this complementary study was initiated. METHODS: Blood
      samples (n = 281) were collected from 64 cubs (3 to 43 days old) whelped by 19
      rabies-immune captive-bred vixens. Sera was collected up to six times from each
      cub. The samples were analysed by a fluorescence focus inhibition technique
      (RFFIT), and antibody titres (nAb) were expressed in IU/ml. The obtained data was
      pooled with previous data sets. Subsequently, a total of 499 serum samples from
      249 cubs whelped by 54 rabies-immune vixens were fitted to a non-linear
      regression model. RESULTS: The disappearance rate of maAb was independent of the
      vixens' nAb-titre. The maAb-titre of the cubs decreased exponentially with age
      and the half-life of the maAb was estimated to be 9.34 days. However, maAb of
      offspring whelped by vixens with high nAb-titres can be detected for longer in
      RFFIT than that of offspring whelped by vixens with relatively low nAb-titres. At
      a mean critical age of about 23 days post partum, maAb could no longer be
      distinguished from unspecific reactions in RFFIT depending on the amount of maAb
      transferred by the mother. CONCLUSIONS: The amount of maAb cubs receive is
      directly proportional to the titre of the vixen and decreases exponentially with
      age below detectable levels in seroneutralisation tests at a relatively early
      age.

PMID- 12069692
TI  - Gene expression profile of HIV-1 Tat expressing cells: a close interplay between
      proliferative and differentiation signals.
AB  - BACKGROUND: Expression profiling holds great promise for rapid host genome
      functional analysis. It is plausible that host expression profiling in an
      infection could serve as a universal phenotype in virally infected cells. Here,
      we describe the effect of one of the most critical viral activators, Tat, in HIV
      1 infected and Tat expressing cells. We utilized microarray analysis from
      uninfected, latently HIV-1 infected cells, as well as cells that express Tat, to
      decipher some of the cellular changes associated with this viral activator.
      RESULTS: Utilizing uninfected, HIV-1 latently infected cells, and Tat expressing
      cells, we observed that most of the cellular host genes in Tat expressing cells
      were down-regulated. The down-regulation in Tat expressing cells is most apparent
      on cellular receptors that have intrinsic receptor tyrosine kinase (RTK) activity
      and signal transduction members that mediate RTK function, including Ras-Raf-MEK
      pathway. Co-activators of transcription, such as p300/CBP and SRC-1, which
      mediate gene expression related to hormone receptor genes, were also found to be
      down-regulated. Down-regulation of receptors may allow latent HIV-1 infected
      cells to either hide from the immune system or avoid extracellular
      differentiation signals. Some of the genes that were up-regulated included co
      receptors for HIV-1 entry, translation machinery, and cell cycle regulatory
      proteins. CONCLUSIONS: We have demonstrated, through a microarray approach, that
      HIV-1 Tat is able to regulate many cellular genes that are involved in cell
      signaling, translation and ultimately control the host proliferative and
      differentiation signals.

PMID- 12069695
TI  - Do multiple outcome measures require p-value adjustment?
AB  - BACKGROUND: Readers may question the interpretation of findings in clinical
      trials when multiple outcome measures are used without adjustment of the p-value.
      This question arises because of the increased risk of Type I errors (findings of
      false "significance") when multiple simultaneous hypotheses are tested at set p
      values. The primary aim of this study was to estimate the need to make
      appropriate p-value adjustments in clinical trials to compensate for a possible
      increased risk in committing Type I errors when multiple outcome measures are
      used. DISCUSSION: The classicists believe that the chance of finding at least one
      test statistically significant due to chance and incorrectly declaring a
      difference increases as the number of comparisons increases. The rationalists
      have the following objections to that theory: 1) P-value adjustments are
      calculated based on how many tests are to be considered, and that number has been
      defined arbitrarily and variably; 2) P-value adjustments reduce the chance of
      making type I errors, but they increase the chance of making type II errors or
      needing to increase the sample size. SUMMARY: Readers should balance a study's
      statistical significance with the magnitude of effect, the quality of the study
      and with findings from other studies. Researchers facing multiple outcome
      measures might want to either select a primary outcome measure or use a global
      assessment measure, rather than adjusting the p-value.

PMID- 12069696
TI  - Single-dose rofecoxib for acute postoperative pain in adults: a quantitative
      systematic review.
AB  - BACKGROUND: Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic
      review of rofecoxib in acute pain examined studies in adults of analgesic
      efficacy over six hours, the amount and quality of the evidence on extended
      duration of analgesia, and the quality and quantity of evidence on adverse
      events. METHODS: Cochrane Library (issue 4, 2001), Biological Abstracts (March
      2002), MEDLINE (March 2002) and PubMed (March 2002) were searched using rofecoxib
      as a free text term. The area under the pain relief versus time curve was
      dichotomized using validated equations to derive the proportion of patients on
      rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was
      used to calculate the number needed to treat for at least 50% pain relief over
      six hours for rofecoxib compared with placebo. Information on duration of
      analgesia and adverse events was also collected. RESULTS: Five included trials
      investigated 1,118 patients, of whom 211 received placebo and 464 received
      rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0
      to 2.6). The weighted mean remedication time was 1.9 hours for placebo (126
      patients), 7.4 hours for ibuprofen 400 mg (97 patients) and 13.6 hours for
      rofecoxib 50 mg (322 patients). CONCLUSION: Rofecoxib at 2-4 times the standard
      daily dose for chronic pain is an effective single dose oral analgesic in acute
      pain. Limitations in trial reporting constrain conclusions about longer duration
      of analgesia and adverse event profile.

PMID- 12069697
TI  - Detection and subtyping of Herpes simplex virus in clinical samples by
      LightCycler PCR, enzyme immunoassay and cell culture.
AB  - BACKGROUND: Prompt laboratory diagnosis of Herpes simplex virus (HSV) infection
      facilitates patient management and possible initiation of antiviral therapy. In
      our laboratory, which receives various specimen types for detection of HSV, we
      use enzyme immunoassay (EIA) for rapid detection and culture of this virus. The
      culture of HSV has traditionally been accepted as the diagnostic 'gold standard'.
      In this study, we compared the use of real time PCR (LightCycler) for
      amplification, detection and subtyping of specific DNA with our in-house
      developed rapid and culture tests for HSV. RESULTS: The LightCycler PCR (LC-PCR)
      detected and subtyped HSV in 99% (66/67) of HSV positive specimens, compared to
      81% (54/67) by rapid antigen EIA or 57% (36/63) by culture. A specimen was
      considered positive when two or more tests yielded HSV identifications or was
      culture positive. Discordant results were confirmed with an in-house developed
      PCR-ELISA or DNA sequence analysis. The typing results obtained with the LC-PCR
      and by culture amplified test were completely concordant. CONCLUSIONS: This study
      showed that the LC-PCR provided a highly sensitive test for simultaneous
      detection and subtyping of HSV in a single reaction tube. In addition to
      increased sensitivity, the LightCycler PCR provided reduced turn-around-times (2
      hours) when compared to enzyme immunoassay (4 hours) or culture (4 days).

PMID- 12069698
TI  - [Fecal elastase-1 determination in the diagnosis of chronic pancreatitis].
AB  - The diagnosis of chronic pancreatitis is based on morphological and functional
      data. To evaluate exocrine function, the secretin-cholecystokinin test is the
      gold standard but this is invasive and frequently unavailable. Recently, fecal
      elastase-1 determination has been investigated as an indirect test of pancreatic
      function. OBJECTIVE: To evaluate the diagnostic value of fecal elastase-1 in
      chronic pancreatitis by comparing it with other indirect methods of evaluating
      pancreatic function such as the urine pancreolauryl test and fecal chymotrypsin
      determination. To do this, we analyzed the three diagnostic methods in four
      groups of patients: group I (14 patients with confirmed chronic pancreatitis);
      group II (5 patients with recurrent episodes of acute alcoholic pancreatitis;
      group III (9 patients with non-pancreatic diarrhea); group IV (8 patients with
      other gastrointestinal diseases). RESULTS: Compared with the control groups
      (groups III and IV), patients in groups I and II presented lower levels of fecal
      elastase-1 (groups I-II: 88 mcg/g, groups III-IV: 635 mcg/g, p < 0.0001), fecal
      chymotrypsin (4.3 U/g and 29.3 U/g, respectively, p < 0.0001), and pancreolauryl
      (14% and 54%, respectively, p < 0,001). In the diagnosis of confirmed chronic
      pancreatitis (group I) the fecal elastase-1 and pancreolauryl tests showed a
      sensitivity of 85.6% and 78.5%, respectively. However, in group II, the most
      sensitive test was the pancreolauryl test (80% versus 60% for the chymotrypsin
      test and only 40% for the fecal elastase-1 test). In contrast, the fecal elastase
      1 test showed the highest specificity (94.1% versus 88.2% for the fecal
      chymotrypsin test and 81.3% for the pancreolauryl test). CONCLUSION: Fecal
      elastase-1 determination is an effective indirect method in the diagnosis of
      patients with advanced chronic pancreatitis. However, when the disease is in the
      early stages, its sensitivity is no greater than that of other indirect tests.
      The greatest advantage of this test is its high specificity.

PMID- 12069699
TI  - [Intravenous 3-day Helicobacter pylori eradication therapy is highly effective in
      patients with bleeding peptic ulcer].
AB  - AIMS: To evaluate the efficacy of 3-day intravenous Helicobacter pylori
      eradication therapy in patients with bleeding peptic ulcer associated with H.
      pylori infection. MATERIAL AND METHOD: We studied 53 patients admitted to
      hospital with bleeding of the upper gastrointestinal tract due to peptic ulcer
      and positive urease test over a 12-month period. After endoscopic diagnosis,
      intravenous pantoprazole (40 mg/12 hours), metronidazole (500 mg/8 hours) and
      amoxicillin-clavulanic acid (1,000 mg/200 mg/8 hours) was administered for 72
      hours. The efficacy of eradication therapy was evaluated by 13C-urea breath test
      at least 2 months after the end of treatment. RESULTS: Fifty-one patients were
      included. Of these, 40 had duodenal ulcer and 11 had gastric ulcer. H. pylori
      eradication was achieved in 87.5% of those with duodenal ulcers and in 63.6% of
      those with gastric ulcers (p = 0.066). No adverse reactions or episodes of
      bleeding recurrence were found and none of the patients withdrew from treatment.
      CONCLUSIONS: The ultra-short course eradication therapy used in this study is
      highly effective. Its efficacy is similar to that of oral treatment and it avoids
      certain problems such as adverse effects and adherence to treatment.

PMID- 12069700
TI  - [Osteomatous jaw lesions in familial adenomatous polyposis].
AB  - The first aim of this study is to assess the frequency of osteomatous jaw lesions
      in patients with a diagnosis of familial adenomatous polyposis (FAP), and a group
      of FAP-relatives from the FAP registry of Majorca (Balearic Islands, Spain). The
      second aim is to study the predictive significance of osteomatous jaw lesions in
      families with FAP. The study included forty-two people. Twenty-five patients and
      seventeen relatives. All individuals underwent pantomography. Osteomatous jaw
      lesions were diagnosed in 68% of FAP-patients, and 6% of FAP-relatives. The
      difference was statistically significant (p < 0.001). The sensitivity was 68%,
      the specificity 94% and positive predictive value 94%. This frequency of
      osteomatous jaw lesions agree with previous studies of FAP-patients (57-82%), but
      differ from these of the previous studies of FAP-relatives (16-18%). The
      available method detect APC (adenomatous polyposis coli) gene mutations in 48-82%
      of FAP families. In the families without detected mutation, non-informative study
      or non-available study, the screening is based in seriated sigmoidoscopy and
      study of the extraintestinals lesions of the FAP syndrome. The frequency of
      osteomatous jaw lesions in FAP-patients is greater than the observed in FAP
      relatives (p < 0.001). Osteomas in families with FAP are of predictive
      significance.

PMID- 12069701
TI  - [Early-onset acute toxic hepatitis induced by intravenous amiodarone
      administration].
AB  - Amiodarone is a widely used and effective long-term antiarrhythmic drug but with
      known adverse effects. Prolonged oral administration of this drug has been
      implicated in numerous hepatic lesions, ranging from isolated, asymptomatic
      transaminase elevation to fulminant, fatal liver failure. Few cases of acute
      hepatotoxicity due to intravenous administration have been reported. We present a
      69-year-old woman with atrial fibrillation who developed acute hepatitis within
      24 hours of amiodarone infusion at the recommended dosage. The drug was withdrawn
      and laboratory findings progressively returned to normal over the following days.
      We analyze a possible mechanism of action for hepatotoxicity and highlight the
      importance of monitoring liver function in patients receiving this drug.

PMID- 12069702
TI  - [Renal amyloidosis as initial clinical manifestation of Crohn's disease].
AB  - We present a 20-year-old man with oligosymptomatic Crohn's disease of the
      terminal ileum complicated by chronic renal insufficiency due to secondary
      amyloidosis. Definitive diagnosis of Crohn's disease was established 7 years
      after the onset of the renal disease as a result of symptoms of intestinal
      obstruction requiring surgery. The affected colonic segment was removed and
      histopathological examination of the surgical specimen confirmed the diagnosis of
      Crohn's disease without identifying intestinal amyloidosis. Despite the surgical
      intervention and the absence of recurrence of inflammatory bowel disease, renal
      insufficiency steadily progressed, and the patient required kidney
      transplantation. The patient's subsequent course was excellent and no recurrence
      of intestinal or renal disease was observed after 8 years of follow-up.

PMID- 12069703
TI  - [Pseudoachalasia and secondary amyloidosis in a patient with rheumatoid
      arthritis].
AB  - Rheumatic diseases cover a wide spectrum of clinical syndromes and frequently
      present with gastrointestinal alterations. Systemic amyloidosis is associated
      with infectious diseases or chronic inflammatory processes such as rheumatoid
      arthritis and it can also affect the gastrointestinal tract. Although esophageal
      involvement is difficult to quantify because its course is frequently
      asymptomatic, systemic amyloidosis is recognized as a cause of motor disorders of
      the esophagus. Typical manometric patterns, including achalasia, are usually
      absent. Esophageal involvement due to amyloid deposits usually corresponds to
      primary amyloidosis as only a few cases of secondary esophageal deposits (type
      AA) have been described. We describe a new case of this exceptional association
      that first presented as dysphagia in a patient with rheumatoid arthritis. The
      initial suspicion of pseudoachalasia led to the definitive diagnosis of secondary
      amyloidosis.

PMID- 12069704
TI  - [Questions and answers on the role of azathioprine and 6-mercaptopurine in the
      treatment of inflammatory bowel disease].

PMID- 12069705
TI  - [Advances in the diagnosis of celiac disease: anti-transglutaminase antibodies
      and intestinal intraepithelial lymphocytes].

PMID- 12069706
TI  - [Chronic hepatitis C in patients coinfected by human immunodeficiency virus].

PMID- 12069707
TI  - [Tuberculosis, another cause of generalized lymphadenopathies in celiac disease].

PMID- 12069709
TI  - [Gravidic cholestasis with transaminase elevation suggestive of acute hepatitis].

PMID- 12069708
TI  - [Endoscopic appearance of the duodenal bulb in adult celiac disease].

PMID- 12069710
TI  - [Kava-induced acute icteric hepatitis].

PMID- 12069719
TI  - Construction of genetic code from evolutionary stability.
AB  - The construction of the genetic code is investigated based on a stability
      principle. The concept and formulation of mutational deterioration (MD) of the
      genetic code is proposed. It is proved that the degeneracies of codon multiplets
      obey the rule to best resist MD. The MD for each ideal multiplet of codons is
      expressed by four parameters and it takes on a minimum value for real
      distributions of codons in the multiplet. Then the global mutational
      deterioration (GMD) of code table is calculated and the minimal code is deduced.
      The domain-like distribution of hydrophobic and hydrophilic amino acids on the
      genetic code is explained from the minimization of GMD. It is demonstrated that
      the standard code is approximately GMD-minimal. By introducing some constraints
      that are related to the initial condition of the system, we have deduced the
      standard genetic code from the minimization of GMD. The minimization shows the
      general trend of evolutionary process to some stable state while the constraints
      reflect a 'frozen accident.' Many deviant codon assignments are also explained
      through MD minimization assuming the changeable degrees of degeneracies for some
      multiplets. So, a possible answer to the question of "Why are synonymous codons
      and amino acids distributed in the code table just as they are?" is given.

PMID- 12069720
TI  - Biased polymers in the origin of life.
AB  - We delve into the study of a Markov chain formalism applied to the thermal
      prebiotic oligomerization of amino acids. We find for the case of only two types
      of electromagnetic interactions, that the steady state attainment by the Markov
      chain is a built in mechanism limiting the expected variability in sequences in a
      population of polymers. Such result may be of importance as it makes more
      accessible the replication of a minimal chemical machinery compatible with life.

PMID- 12069721
TI  - An observation of the initial stage towards a symbiotic relationship.
AB  - Two well-characterized and phylogeneticaly different species, Escherichia coli
      and Dictyostelium discoideum, were used as the model organisms. When the two
      species were mixed and allowed to grow on minimal agar plates at 22 degrees C,
      remarkably, the two species achieved a state of coexistence at an average of 2-4
      weeks. In addition, the emerged colonies housing the coexisting species had a
      mucoidal nature that was not observed from its origin. Moreover, the state of
      coexistence was confirmed to be stable, and so was the mucoidal nature of the
      emerged colonies. Comparing with the pure E. coli origin, the mucoidal colony
      showed a significant increase in higher molecular weight extracellular
      components, with polysaccharides as the major constituent. Qualitative analysis
      of the monosaccharide contents in the extracellular components of the mucoidal
      colony revealed not only a significant increase in the glucose content, but also
      significant amount of additional xylose and galactose. The system permits the
      initial stages of the development of relationship between two species be captured
      within a short period of time. This feature, together with being simple and
      reproducible in laboratory conditions, provides a new model system for the study
      of symbiosis, especially when initial stages are concerned.

PMID- 12069722
TI  - Controllability of selection-mutation systems.
AB  - The well-known Fisher type selection-mutation model is studied from the point of
      view of mathematical systems theory. Mutation rates are considered as control
      functions. Based on a general sufficient condition for local controllability of
      non-linear systems with invariant manifold, a method is proposed to guarantee the
      controllability of the considered population into a polymorphic equilibrium.

PMID- 12069723
TI  - From molecular biology to nanotechnology and nanomedicine.
AB  - Great progress in the development of molecular biology techniques has been seen
      since the discovery of the structure of deoxyribonucleic acid (DNA) and the
      implementation of a polymerase chain reaction (PCR) method. This started a new
      era of research on the structure of nucleic acids molecules, the development of
      new analytical tools, and DNA-based analyses. The latter included not only
      diagnostic procedures but also, for example, DNA-based computational approaches.
      On the other hand, people have started to be more interested in mimicking real
      life, and modeling the structures and organisms that already exist in nature for
      the further evaluation and insight into their behavior and evolution. These
      factors, among others, have led to the description of artificial organelles or
      cells, and the construction of nanoscale devices. These nanomachines and
      nanoobjects might soon find a practical implementation, especially in the field
      of medical research and diagnostics. The paper presents some examples,
      illustrating the progress in multidisciplinary research in the nanoscale area. It
      is focused especially on immunogenetics-related aspects and the wide usage of DNA
      molecules in various fields of science. In addition, some proposals for
      nanoparticles and nanoscale tools and their applications in medicine are reviewed
      and discussed.

PMID- 12069724
TI  - Evolution and degeneration of eukaryotic DNA replication system.
AB  - Several molecular forms of DNA polymerases have been identified in eukaryotic
      cells. Although three DNA polymerases alpha, delta, and epsilon, have been well
      studied and indicated to be involved in nuclear DNA replication process, it
      remains unclear how this hetero-polymerase system might have arisen. Here I wish
      to consider its past and future, viewed in the context of molecular evolution.
      Comparative analysis has revealed some nucleotides and/or amino acids to be
      conserved in DNA polymerase delta, in polymerase domains III and IV, which have
      disappeared in DNA polymerase alpha. Furthermore, the codon usage for serine
      residues in conserved domains of DNA polymerase alpha varies and is not as
      conservative as for DNA polymerase delta. Recently and in the present study, I
      have reported that DNA polymerase delta could substitute for the function of DNA
      polymerase alpha in vitro, and proposed the hypothesis that eukaryotic DNA
      polymerase alpha arose due to symbiotic contacts. This 'exogenous' polymerase
      would be expected to be excluded from the eukaryotic DNA replication system, and
      my analysis in the present study suggests it is about to degenerate.

PMID- 12069725
TI  - Effective dimensionality of large-scale expression data using principal component
      analysis.
AB  - Large-scale expression data are today measured for thousands of genes
      simultaneously. This development is followed by an exploration of theoretical
      tools to get as much information out of these data as possible. One line is to
      try to extract the underlying regulatory network. The models used thus far,
      however, contain many parameters, and a careful investigation is necessary in
      order not to over-fit the models. We employ principal component analysis to show
      how, in the context of linear additive models, one can get a rough estimate of
      the effective dimensionality (the number of information-carrying dimensions) of
      large-scale gene expression datasets. We treat both the lack of independence of
      different measurements in a time series and the fact that that measurements are
      subject to some level of noise, both of which reduce the effective dimensionality
      and thereby constrain the complexity of models which can be built from the data.

PMID- 12069726
TI  - A bioinformatics based approach to discover small RNA genes in the Escherichia
      coli genome.
AB  - The recent explosion in available bacterial genome sequences has initiated the
      need to improve an ability to annotate important sequence and structural elements
      in a fast, efficient and accurate manner. In particular, small non-coding RNAs
      (sRNAs) have been difficult to predict. The sRNAs play an important number of
      structural, catalytic and regulatory roles in the cell. Although a few groups
      have recently published prediction methods for annotating sRNAs in bacterial
      genome, much remains to be done in this field. Toward the goal of developing an
      efficient method for predicting unknown sRNA genes in the completed Escherichia
      coli genome, we adopted a bioinformatics approach to search for DNA regions that
      contain a sigma70 promoter within a short distance of a rho-independent
      terminator. Among a total of 227 candidate sRNA genes initially identified, 32
      were previously described sRNAs, orphan tRNAs, and partial tRNA and rRNA operons.
      Fifty-one are mRNAs genes encoding annotated extremely small open reading frames
      (ORFs) following an acceptable ribosome binding site. One hundred forty-four are
      potentially novel non-translatable sRNA genes. Using total RNA isolated from E.
      coli MG1655 cells grown under four different conditions, we verified transcripts
      of some of the genes by Northern hybridization. Here we summarize our data and
      discuss the rules and advantages/disadvantages of using this approach in
      annotating sRNA genes on bacterial genomes.

PMID- 12069727
TI  - Parametric scaling from species to growth-form diversity: an interesting analogy
      with multifractal functions.
AB  - We propose a measure of divergence from species to life-form diversity aimed at
      summarizing the ecological similarity among different plant communities without
      losing information on traditional taxonomic diversity. First, species and life
      form relative abundances within a given plant community are determined. Next,
      using Renyi's generalized entropy, the diversity profiles of the analyzed
      community are computed both from species and life-form relative abundances.
      Finally, the speed of decrease from species to life-form diversity is obtained by
      combining the outcome of both profiles. Interestingly, the proposed measure shows
      some formal analogies with multifractal functions developed in statistical
      physics for the analysis of spatial patterns. As an application for
      demonstration, a small data set from a plant community sampled in the
      archaeological site of Paestum (southern Italy) is used.

PMID- 12069728
TI  - Partial automation of database processing of simulation outputs from L-systems
      models of plant morphogenesis.
AB  - Models of plant architecture allow us to explore how genotype environment
      interactions effect the development of plant phenotypes. Such models generate
      masses of data organised in complex hierarchies. This paper presents a generic
      system for creating and automatically populating a relational database from data
      generated by the widely used L-system approach to modelling plant morphogenesis.
      Techniques from compiler technology are applied to generate attributes (new
      fields) in the database, to simplify query development for the recursively
      structured branching relationship. Use of biological terminology in an
      interactive query builder contributes towards making the system biologist
      friendly.

PMID- 12069730
TI  - Letter from Dutch doctor in England.

PMID- 12069729
TI  - Cluster analysis of the codon use frequency of MHC genes from different species.
AB  - The relative synonymous codon use frequency of 135 MHC genes from four mammal
      species (Homo sapiens, Pan troglodyte, Macaca mulanta and Rattus norvegicus) is
      analyzed using a hierarchical cluster method. The result suggests that gene
      function is the dominant factor that determines codon usage bias, while species
      is a minor factor that determines further difference in codon usage bias for
      genes with similar functions. The conclusion may be useful in gene classification
      and gene function prediction.

PMID- 12069731
TI  - Prenatal telemedicine: clinical experience with conventional and computerised
      antepartum telecardiotocography.
AB  - OBJECTIVE: To describe the clinical results of the first working year of a
      telemedicine project based on computerised telecardiotocography. STUDY DESIGN:
      The project is based on the "TOCOMAT" system, which remotely recorded and
      processed cardiotocograms performed at five peripheral units from high and low
      risk patients, then transferred them to a University Operative Centre, where they
      were displayed, stored and analysed by the 2CTG system and by two expert
      observers. RESULTS: 457 traces were analysed. The perinatal outcome was good,
      except for two high-risk fetuses. Both patients and carers had favourable
      reactions. The management of patients with pregnancies at risk was improved by
      the interaction of the physicians involved with the experts at the Operative
      Centre. CONCLUSIONS: Telemedicine could enable the decentralization of perinatal
      surveillance, improving quality of life for pregnant and newborn and
      rationalizing costs for prenatal care.

PMID- 12069732
TI  - Does preterm cervical dilatation imply imminent labor in multifetal pregnancies?
AB  - OBJECTIVE: Women with multifetal pregnancies are at increased risk of preterm
      labor and delivery compared with singleton pregnancies. Presentation with
      advanced cervical dilatation of 3-4 cm is generally regarded as being in the
      midst of the first stage of labor. The purpose of this report is to present our
      experience in cases of advanced cervical dilatation and arrested preterm labor in
      multifetal pregnancies. METHODS: This study is a retrospective analysis of
      threatened preterm deliveries in women with multifetal pregnancies. Fifteen cases
      with advanced cervical dilatation that remained undelivered for at least 10 days
      are presented and reviewed. RESULTS: Out of 1219 women presenting with multifetal
      pregnancies to the high-risk maternity unit, 15 women who presented with advanced
      cervical dilatation of 3-5 cm and remained undelivered for at least 10 days were
      identified. Eight women presented with twins and seven with triplets. The mean
      latency period to delivery was 21.7 days (range 10-43 days). The mean gestational
      age at diagnosis was 31.3 weeks (range 26.3-35.3 weeks). The mean gestational age
      at delivery was 34.5 weeks (range 29.5-38.0 weeks). Twelve women delivered
      vaginally in this group, giving a cesarean section rate of 20%. CONCLUSIONS: In
      the women presented in this series advanced cervical dilatation did not lead
      directly to preterm labor and delivery, we believe due to their having a
      multifetal gestation. It is possible that dilatation of the cervix in these cases
      is not a result of preterm labor but rather a relative cervical incompetence
      resulting from overdistention of the uterus in twins or higher-order gestations.
      This phenomenon may be underdiagnosed because of a tendency to forego frequent
      digital examinations remote from term without a clear indication. More
      information is therefore needed on the mechanism of cervical change during
      multifetal pregnancy.

PMID- 12069733
TI  - Cost-effectiveness analysis of gestational diabetes mellitus screening in France.
AB  - OBJECTIVE: To compare three strategies for gestational diabetes screening (i)
      screening of high-risk pregnant women with the 50 g oral glucose tolerance test
      (OGTT); (ii) screening of all pregnant women with the 50 g OGTT; (iii) screening
      of all pregnant women according to the 75 g OGTT. STUDY DESIGN: Cost
      effectiveness analysis. The outcome measures, i.e. macrosomia, prematurity,
      perinatal mortality, hypertensive disorders rates were estimated from published
      studies and the costs from a prospective study involving 120 pregnant women.
      RESULTS: Compared to the first strategy, the cost to obtain one unit of
      additional effectiveness with the second screening strategy, was up to 1.1 times
      more expensive, and with the third strategy was up to 3.7 times more expensive.
      CONCLUSION: The costs per case prevented reflect a favourable cost-effectiveness
      ratio (CER) for screening of high-risk pregnant women by 50 g oral glucose test.

PMID- 12069734
TI  - C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of
      adverse pregnancy outcomes?
AB  - OBJECTIVE: The hypothesis was that fasting C-peptide and insulin values, during
      an oral glucose tolerance test (OGTT), might allow an estimation of the increased
      risk for gestational hypertension (GH) and fetal macrosomia. STUDY DESIGN: Two
      hundred and six consecutive patients were submitted to an OGTT. Thirty-five
      developed gestational hypertension and 29 delivered large-for-gestational-age
      (LGA) newborns. Plasma glucose levels (mg/dl) and insulin levels (microU/ml) were
      measured fasting and after 60, 120 and 180 min C-peptide fasting levels (ng/ml)
      were also measured. RESULTS: Twenty-five patients were excluded, 181 were
      enrolled. According to the OGTT, 143 patients were classified as normal, 26 were
      found affected by gestational diabetes (GD) mellitus, and 12 had impaired
      gestational glucose tolerance (IGGT). Hypertensive women exhibited higher 60 and
      120 min insulin values than the normotensive group (128.3+/-69.9 microU/ml versus
      86.2+/-58.3 microU/ml, P<0.05; 104.9+/-66.4 microU/ml versus 78.7+/-56.5
      microU/ml, P<0.05).C-peptide cut-off at 2.9 ng/ml resulted predictive for
      patients delivering large-for-gestational-age newborns (OR=3.42, 95% CI=1.59
      7.39). CONCLUSIONS: C-peptide and insulin may be used as indicators of risk for
      the development of complications in late pregnancy.

PMID- 12069735
TI  - Antioxidant enzyme activities are decreased in preterm infants and in neonates
      born via caesarean section.
AB  - OBJECTIVES: To investigate the antioxidant defense potential of human neonates
      according to gestational age and mode of delivery. STUDY DESIGN: Four study
      groups were established, full-term normal spontaneous vaginal delivery (FT-NSVD,
      n=24), full-term caesarean section (FT-CS, n=19), preterm normal spontaneous
      vaginal delivery (PT-NSVD, n=15) preterm caesarean section (PT-CS, n=21). The
      activity of catalase (CAT), glutathion peroxidase (GPX), Cu/Zn superoxide
      dismutase (Cu/Zn-SOD) were determined from cord blood. Statistical analysis was
      made by ANOVA. RESULTS: CAT activity was significantly higher in full-term than
      in preterm newborns. In both the categories, neonates born via caesarean section
      had significantly lower CAT activities. GPX activity was significantly higher in
      the FT-NSVD group than in any other group. Cu/Zn-SOD activity was significantly
      higher in full-term neonates than in preterms and no difference was found related
      to the mode of delivery. CONCLUSIONS: Prematurity and caesarean section may cause
      a deficiency of antioxidant defense in human newborn.

PMID- 12069736
TI  - Clinical evaluation of three different gonadotrophin-releasing hormone analogues
      in an IVF programme: a prospective study.
AB  - The efficacy and safety of short acting buserelin and nafarelin intranasal spray
      were compared to long acting leuprorelin depot intramuscular or subcutaneous
      injection in this prospective study of 157 women undergoing controlled ovarian
      hyperstimulation (COH) for in-vitro fertilisation (IVF). Patients were allocated
      to three groups to receive buserelin 150 microg nasal spray three times daily
      (Group B), nafarelin nasal spray 400 microg twice daily (Group N), or leuprorelin
      depot 3.75 mg once by intramuscular or subcutaneous injection (Group L) for
      pituitary desensitisation prior to commencing COH with human menopausal
      gonadotrophins (hMG) according to the Centre's protocol. The mean (+/-S.D.) age
      (years) (32.6+/-3.8: Group B, 32.1+/-3.3: Group N versus 32.1+/-3.3: Group L);
      mean (+/-S.D.) total dosage of hMG (ampoules) (37.5+/-16.1: Group B, 39.8+/-14.2:
      Group N versus 41.9+/-12.6: Group L) and mean daily dosage of hMG (ampoules)
      (3.1: Group B, 2.8: Group N versus 3.0: Group L) seen were not statistically
      significantly different. The duration between starting the different
      gonadotrophin-releasing hormone (GnRHa) and the beginning of the next menstrual
      period was also not seen to be statistically significantly different between the
      three groups (Group B: 10+/-5.5, Group N: 9.1+/-4.1 versus Group L: 8.2+/-3,
      days). The number of abandoned cycles was higher in Group L (17% versus 11.8%:
      Group B and 11.3%: Group N) but this difference did not reach statistical
      significance. The clinical pregnancy rates per oocyte retrieval and per embryo
      transfer procedure were respectively, 31.1, 35% in Group B, 12.8, 14% in Group N
      versus 20.5, 23.7 in Group L and were not seen to be statistically significantly
      different even when ongoing pregnancy rates were compared. Apart from a
      statistically significantly greater incidence of allergic nasal reactions in the
      nafarelin group (P=0.001), all other side-effects were not shown to be
      statistically significantly different between the three groups. We conclude that
      a single dose of leuprorelin depot can be considered to be as an equally
      effective alternative to multiple doses of buserelin or nafarelin for pituitary
      desensitisation in women undergoing COH for IVF.

PMID- 12069737
TI  - Increasing the gonadotrophin dose in the course of an in vitro fertilization
      cycle does not rectify an initial poor response.
AB  - OBJECTIVE: To evaluate the value of increasing the gonadotrophin dose after 5
      days of controlled ovarian stimulation in IVF patients who show an initial poor
      response to stimulation. SUBJECTS AND METHODS: We identified all IVF cycles
      between January 1992 and March 1996 in which ovarian response after 5 days of
      controlled ovarian hyperstimulation (COH) with 225-300 IU per day of human
      menopausal gonadotrophins (hMG; Metrodin or Pergonal) was monitored by
      measurement of serum estradiol concentrations (n=596 patients). According to
      estradiol concentration, the daily dose of hMG was doubled or increased to 450 IU
      in 193 patients (group A) or maintained the same in 403 patients (group B).
      Further cycle monitoring was achieved using serial ultrasound and serum estradiol
      measurements. RESULTS: The two groups were age-matched. Group A patients
      experienced a higher cancellation rate despite having a higher mean number of hMG
      ampoules (59.5 versus 36.2) and a longer duration of stimulation (12.2 versus
      10.8 days). They achieved lower levels of serum estradiol on days 9 and 10 of
      stimulation, produced a lower mean number of oocytes per retrieval (5.8 versus
      8.9) and had a lower clinical pregnancy rate per cycle (8.3 versus 23.4%)
      compared to group B. All differences were statistically significant. CONCLUSION:
      The poor outcome of cycles with initial low response to COH appears not to be
      averted by doubling or increasing the hMG dose after 5 days of stimulation.

PMID- 12069738
TI  - Could induced apoptosis of human granulosa cells predict in vitro fertilization
      embryo transfer outcome? A preliminary study of 25 women.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between
      induced apoptosis of human luteinized granulosa cells (GCs) and in vitro
      fertilization (IVF) outcome. STUDY DESIGN: We induced apoptosis with interferon
      gamma and an anti-human Fas antibody in cultured GCs isolated from follicular
      fluids coming from 25 different women undergoing 25 consecutive IVF cycles. After
      examination of 1000 GCs stained by DAPI with a fluorescent microscope, we
      determined the percentages of apoptotic GCs. Ovarian, endometrial and IVF
      parameters were recorded for every woman. RESULTS: We classified the women
      according to their induced GCs apoptosis percentages in two groups. Group 1 with
      a low percentage of apoptotic GCs (11.6+/-4.8%) had a significantly higher
      pregnancy rate (P<0.05) than group 2 with a high percentage of apoptotic GCs
      (59.5+/-14.8%). No other statistically significant differences were observed.
      CONCLUSION: Resistance of human GCs to apoptosis might be implicated in IVF
      outcome.

PMID- 12069740
TI  - The effect of adnexal surgery on the ovarian response to stimulation in in vitro
      fertilization.
AB  - OBJECTIVES: The effect of adnexal surgery on ovarian function is a controversial
      issue of high clinical significance. The purpose of this study was to assess the
      effect of adnexal surgery on ovarian function. STUDY DESIGN: All patients who
      underwent adnexal surgery in our department during an 8-year period (all records
      were obtained from the hospital database between January 1991 and December 1998)
      were cross-matched with our in vitro fertilization (IVF) database. We compared
      the baseline hormonal levels and the patients' response to IVF stimulation
      (assessed by the total amount of gonadotropins, maximal estradiol (E2) levels,
      number of retrieved and fertilized oocytes). RESULTS: Sixty-four consecutive
      patients who underwent adnexal surgery were compared with 68 matched controls.
      Neither of the analyzed parameters were affected by the tubal surgery.
      CONCLUSIONS: We conclude from our study adnexal surgery is not detrimental to
      ovarian function.

PMID- 12069739
TI  - Sex hormone profile and endometrial cancer risk in primary biliary cirrhosis: a
      case-control study.
AB  - OBJECTIVE: To investigate the sex hormone profile and endometrial histology in
      primary biliary cirrhosis (PBC). STUDY DESIGN: A prospective case-control study.
      Twenty-two females with PBC and 22 sex- and age-matched healthy controls
      underwent complete gynaecological examination including endometrial biopsy and a
      sex hormone serological profile including: oestrone, 17-beta oestradiol,
      testosterone, progesterone, dehydroepiandrosterone sulphate (DHEA-S) and sex
      hormone binding protein (SHBG). The sex hormone profile was evaluated with
      respect to the body mass index (BMI), anthropometric measurements and endometrial
      histological/cytological patterns in each case. Statistical analysis was done
      with the chi-squared method, Student's t-test for unpaired data, linear
      regression analysis, Spearman's rank correlation test and stepwise multiple
      regression analysis. RESULTS: The BMI was comparable in the two groups, while PBC
      cases had significantly smaller subscapular, waist, bicipital, tricipital and
      calf fold measurements than controls. Testosterone serum levels were
      significantly lower in PBC cases than in controls (0.9+/-0.6 versus 1.4+/-0.7
      mmol/l, P<0.03), whereas SHBG was significantly higher than in controls (88.6+/
      72.1 versus 63.6+/-27.6, P<0.005). No significant differences between the two
      groups were found for oestrone, 17-beta oestradiol, DHEA-S, and progesterone
      levels. No difference patterns were observed in endometrial
      histological/cytological patterns. Multiple regression analysis identified SHBG
      as an independent variable associated with PBC. CONCLUSIONS: Changes in sex
      hormone profile are secondary to hepatic dysfunction in PBC. Females with PBC do
      not appear to carry a higher risk of endometrial cancer.

PMID- 12069741
TI  - Results of tension-free vaginal tape in patients with or without vaginal
      hysterectomy.
AB  - OBJECTIVE: To assess complications and cure rates of tension-free vaginal tape
      (TVT) procedure performed with or without vaginal hysterectomy. STUDY DESIGN:
      Retrospective comparison of 41 women with urinary incontinence treated by a TVT
      procedure alone and 40 combined with vaginal hysterectomy. Objective cure was
      evaluated by clinical and urodynamic examination and by the contilife
      questionnaire. All patients were operated under regional anesthesia. RESULTS: The
      two groups were similar in age, parity, menopausal status and type and severity
      of incontinence. There was no difference in overall complication rates. In the
      TVT-hysterectomy group, there was a trend towards more bladder perforation
      (P=0.09). Post-operative urinary flow was lower in the TVT-hysterectomy group: 14
      versus 24 ml/pc (P=0.02). The mean follow-up was similar: 23 and 25 months,
      respectively. No difference in objective and subjective cure rates was found
      between TVT group and TVT-hysterectomy group: 97.6% versus 92.5% and 68.3% versus
      75%, respectively. CONCLUSION: TVT is a safe and effective surgical treatment of
      urinary incontinence. The association of the procedure with vaginal hysterectomy
      gave similar short-term objective and subjective cure rates than TVT technique
      alone.

PMID- 12069742
TI  - Long-term results after neovagina creation in Mayer-Rokitanski-Kuster-Hauser
      syndrome by Vecchietti's operation.
AB  - OBJECTIVES: To evaluate the long-term results after Vecchietti's operation. STUDY
      DESIGN: Twenty Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome patients underwent
      creation of a neovagina using Vecchietti's operation by laparotomy (17 cases) and
      laparoscopy (3 cases). RESULTS: The mean age of the patients was 21 years (16
      34). After 66 months (24-156) of follow-up, the mean length x diameter of the
      neovagina was 8.2 cm x 2.8 cm. The neovaginal epithelium was macroscopically
      similar to normal vaginal mucosa, except for one patient who had subsequently
      undergone insertion of skin graft. Post-operative sexual behavior revealed sexual
      desire and pleasure (100%), lubrication (94%), clitoral orgasm (87%) and vaginal
      mediated orgasm (69%). Finally, 16 patients out of 18 (89%) were completely
      satisfied with the results of the operation. CONCLUSION: Vecchietti's operation
      may be suggested as one of the choice of treatments to correct vaginal aplasia in
      young MRKH syndrome patients.

PMID- 12069744
TI  - Postpartum urinary symptoms: prevalence and risk factors.
AB  - OBJECTIVES: To assess the prevalence of urinary symptoms, the relationship
      between urinary symptoms and vaginal descent, and the association between urinary
      symptoms and obstetric factors. STUDY DESIGN: Five hundred and thirty-seven women
      were interviewed and underwent a urogynaecological evaluation 3 months after
      vaginal delivery. Quantitative-type variables were subjected to Student's t test.
      Simple logistic regression analyses were carried out on the symptoms studied as a
      function of risk factors. RESULTS: 8.2% of primiparae showed stress urinary
      incontinence and multiparae in 20% (P=0.0001); urge incontinence was present in
      5.5% of primiparae and in 13% of multiparae (P=0.004). Significant correlations
      were found among operative vaginal delivery, dysuria (P=0.048) and frequency
      (P=0.036). Urinary incontinence appeared associated with induced labour with
      prostaglandins (P=0.018) and with general maternal factors, such as parity
      (P=0.001) and elevated weight at the beginning of pregnancy (P=0.019).
      CONCLUSIONS: It is likely that the pathogenesis of postpartum urinary
      incontinence includes not only the effects of pelvic floor trauma on
      urethrovesical mobility under stress, but also a deficiency in urethral
      resistance caused by drugs, such as prostaglandins.

PMID- 12069743
TI  - Questionnaire as diagnostic tool in chronic pelvic pain (CPP): a pilot study.
AB  - OBJECTIVES: No standard screening instrument is available enabling physicians to
      assign the diagnosis chronic pelvic pain (CPP) to women with lower abdominal
      pain. Therefore, our aim was to evaluate an easy-to-use questionnaire, which can
      be applied as a validated primary screening test for diagnosing CPP. STUDY
      DESIGN: From the general female population, 577 women completed a questionnaire
      addressing chronic symptoms in the pelvic region. Included were (amongst others)
      questions on lower abdominal pain, low back pain, voiding symptoms, dyspareunia,
      pelveo-perineal dysesthetic feelings and evacuation problems. Serious chronic
      lower abdominal pain of unknown origin was considered as CPP. Three criteria were
      applied to validate the questionnaire: construct validity, comparison with
      results of a previous study and content validity. In addition, the internal
      consistency was checked to ascertain the reliability of the questionnaire.
      RESULTS: All items, with the exception of those concerning voiding symptoms and
      dyspareunia, withstood the validity tests applied, were interrelated and occurred
      significantly more often in women with CPP than those without. There were no
      significant differences in the frequency of the occurrence of low back pain,
      dyspareunia and evacuation problems between CPP women in the current community
      study and outpatients diagnosed with CPP in an earlier study performed at the
      University Hospital Rotterdam. Compared to our current study group, pelveo
      perineal dysesthesia (PPD) and voiding symptoms were significantly more often
      reported by the CPP outpatients. CONCLUSION: The CPP questionnaire can be
      considered as a validated tool for primary screening of CPP.

PMID- 12069745
TI  - Foetal growth restriction in the next pregnancy after uterine artery embolisation
      for post-partum haemorrhage.

PMID- 12069746
TI  - Vaginal stenosis with hematocolpometra, complicating chronic graft versus host
      disease.

PMID- 12069747
TI  - Sacrospinous cervico-colpopexy with follow-up 2 years after successful pregnancy.
AB  - Sacrospinous cervico-colpopexy was performed for marked uterine prolapse in a
      young woman desirous of childbearing. Follow-up at 2 years following elective
      cesarean delivery revealed a well-supported cervix and vaginal vault at the level
      of the ischial spine. Although this represents an appropriate management, more
      information is still needed before the optimal mode of delivery following
      successful uterine prolapse repair can be established.

PMID- 12069748
TI  - Lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood.
AB  - OBJECTIVE: To report a case of lymphangioma of the ovary after radiation due to
      Wilms' tumor in the childhood. PATIENT: A 19-year-old nulliparous female.
      INTERVENTIONS: The vaginal ultrasound showed the left ovary enlarged to 4.4 cm x
      2.9 cm x 4.5 cm in size including a 3.5 cm x 2.6 cm x 3.2 cm measuring cystic
      solid tumor without hypervascularity. For exclusion of a malignant tumor, a
      laparoscopy for excision of the tumor and deep incision of the left ovary with a
      bipolar needle was performed to exclude deeper tumor of stromal origin. The
      histological examination of the tissue showed a lymphangioma beside normal
      ovarian tissue. CONCLUSION: To our knowledge, this is the first report of
      lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood.
      The impact of this finding on the patient's fertility remains unclear. As in
      other organs exposed to radiation, lymphangioma can also occur in the ovary.
      Careful follow up should be considered to this patients, because malignant
      transformation can not be excluded.

PMID- 12069750
TI  - Specialist life: Lazlo Lampe.

PMID- 12069752
TI  - Collagens, integrins, and the discoidin domain receptors in arterial occlusive
      disease.
AB  - The collagen matrix constitutes a major portion of the vascular extracellular
      matrix and imparts blood vessels with tensile strength and, even more important,
      modulates smooth muscle cell (SMC) responses via specific receptors and signaling
      pathways. This review is focused on the interactions of SMCs with the collagen
      matrix, how these interactions are involved in sensing the local environment, and
      the receptors that mediate these processes. Better understanding of the pathways
      involved in cell matrix interactions promises to provide novel therapeutic
      targets and treatment strategies for the prevention of arterial occlusive
      diseases such as atherosclerosis and restenosis.

PMID- 12069753
TI  - Orchestration of coagulation protease signaling by tissue factor.
AB  - Protease-activated receptors (PARs) are vascular sensors for signaling of the
      trypsinlike coagulation serine proteases that play key roles in cardiovascular
      medicine. In the initiation phase of coagulation, tissue factor (TF) orchestrates
      the assembly of VIIa with substrate X, forming a ternary complex in which product
      Xa is generated. The resulting TF-VIIa-Xa complex is an efficient activator of
      PAR1 and PAR2. TF initiation of the coagulation cascade is thus intimately linked
      to inflammatory cell signaling. Inflammation is an increasingly appreciated
      component of the vulnerable atherosclerotic plaque. Targeting inflammatory cell
      signaling events of the coagulation system may become an important aspect of
      efforts to improve antithrombotic therapy.

PMID- 12069754
TI  - Arterial inflammation and atherosclerosis.
AB  - Arterial inflammation is a significant component of atherosclerotic disease and
      it has been suggested that specific immune responses directed against
      autoantigens or pathogen-derived antigens presented in the vascular wall could
      initiate and/or maintain atherosclerotic processes. Atherogenic cofactors such as
      altered cholesterol metabolism may not only impact locally on inflammatory
      responses in atherosclerotic lesions, but may also alter general immune
      responsiveness. The evidence to date suggests that the mutual chronic
      perpetuation of immune mediated vascular inflammation and cholesterol-induced
      atherosclerosis is a key step in atherogenesis.

PMID- 12069755
TI  - Phosphorylation of LRP1: regulation of transport and signal transduction.
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is a member of the low
      density lipoprotein receptor family. Members of this family were once thought to
      be involved exclusively in receptor-mediated uptake of extracellular molecules,
      including lipoproteins and proteases. This article reviews recent work that
      indicates that LRP1 is phosphorylated on both serine and tyrosine residues.
      Tyrosine-phosphorylated LRP1 is specifically associated with the cellular docking
      protein Shc. The results suggest that ligand internalization by LRP1 is regulated
      by phosphorylation. In addition, LRP1 is now, like several of its close
      relatives, implicated in signal transduction.

PMID- 12069756
TI  - Regulation of ryanodine receptors via macromolecular complexes: a novel role for
      leucine/isoleucine zippers.
AB  - Defective calcium (Ca(2+)) signaling, manifest as a loss of excitation
      contraction (EC) coupling gain in cardiac muscle, likely plays an important role
      in the pathophysiology of human heart failure. The mechanism underlying this loss
      of cardiac EC coupling gain involves altered regulation of the cardiac ryanodine
      receptor (RyR2), the major sarcoplasmic reticulum Ca(2+) release channel in the
      heart. This altered regulation of RyR2 is due, in part, to hyperphosphorylation
      of the channel by cyclic adenosine monophosphate-dependent protein kinase A
      (PKA). PKA phosphorylation of RyR2 is controlled by a macromolecular signaling
      complex that targets PKA and two phosphatases (PP1 and PP2A) to the channel. The
      targeting of PKA, PP1, and PP2A to RyR2 is dependent on the binding of targeting
      proteins to the channel via highly conserved leucine/isoleucine zippers (LIZs).
      Formation of an ion channel macromolecular signaling complex is a novel role of
      LIZs. Recognition of this new function for LIZ motifs has provided a road map for
      rapidly identifying components of the RyR2 macromolecular signaling complex that
      play a key role in regulating normal cardiac physiology as part of the "fight or
      flight" response. The components of the RyR2 macromolecular signaling complex are
      also novel targets for heart failure and cardiac arrhythmia therapeutics.

PMID- 12069757
TI  - The cholesterol mobilizing transporter ABCA1 as a new therapeutic target for
      cardiovascular disease.
AB  - Atherosclerotic cardiovascular disease remains the leading cause of morbidity and
      mortality in Western societies. A hallmark of the developing atherosclerotic
      lesion is the appearance of cholesterol-laden macrophages in the artery wall. A
      cell membrane transporter called ABCA1 mediates the removal of excess cholesterol
      from macrophages into the lipoprotein pathway. This makes ABCA1 a promising new
      therapeutic target for reducing cholesterol deposits in tissues, eliminating
      excess cholesterol from the body, and preventing cardiovascular disease.

PMID- 12069758
TI  - Corticotropin-releasing hormone-related peptides and receptors: emergent
      regulators of cardiovascular adaptations to stress.
AB  - Since its discovery 2 decades ago, potent effects of corticotropin-releasing
      hormone (CRH) on the heart and vasculature have been consistently observed. The
      recent discoveries of novel CRH-related peptides residing in the heart and a
      distinct cardiac CRH receptor (CRH-R2), have renewed interest in the role of the
      CRH family on cardiovascular function. This review highlights the emerging view
      of a peripheral, cardiac CRH system and its potential relevance in mediating the
      adaptive response of the heart to stress.

PMID- 12069759
TI  - KCNE regulation of KvLQT1 channels: structure-function correlates.
AB  - K(+) channels play a central role in determining resting membrane potential and
      cellular excitability. There is growing recognition that the channels exist not
      as independent units but as macromolecular complexes able to integrate a plethora
      of cellular signals to fine-tune channel activities. Interaction of K(+) channels
      with accessory proteins and subunits is increasingly reported as providing
      mechanisms for channels to respond to a variety of stimuli beyond just changes in
      membrane potential. One such association is that between some voltage-gated K(+)
      channels and the proteins encoded by the KCNE family of genes. The significance
      of these interactions is manifest in reports of genetic disorders such as the
      Long QT Syndrome linked to KCNE mutations and proarrhythmic drug susceptibilities
      from KCNE polymorphisms. The mechanism by which KCNE-encoded proteins control
      channel behavior is an emerging story. This article reviews some of the recent
      work addressing the prototypical KCNE-channel interaction between minK and
      KvLQT1.

PMID- 12069761
TI  - Combining biometric and symbolic models for customized, automated prosthesis
      design.
AB  - In a previous paper [Artif. Intell. Med. 5 (1993) 431] we described RaPiD, a
      knowledge-based system for designing dental prostheses. The present paper
      discusses how RaPiD has been extended using techniques from computer vision and
      logic grammars. The first employs point distribution and active shape models
      (ASMs) to determine dentition from images of casts of patient's jaws. This
      enables a design to be customized to, and visualised against, an image of a
      patient's dentition. The second is based on the notion of a path grammar, a form
      of logic grammar, to generate a path linking an ordered sequence of
      subcomponents. The shape of an important and complex prosthesis component can be
      automatically seeded in this fashion. Combining these models now substantially
      automates the design process, beginning with a photograph of a dental cast and
      ending with an annotated and validated design diagram ready to guide manufacture.

PMID- 12069760
TI  - Evaluation of two different models of semi-automatic knowledge acquisition for
      the medical consultant system CADIAG-II/RHEUMA.
AB  - As part of a plan to promote semi-automatic knowledge acquisition for the medical
      consultant system CADIAG-II/RHEUMA, this study sought to explore and cope with
      the variability of results that may be anticipated when performing knowledge
      acquisition with patient data from different patient settings. Patient data were
      drawn both from a published study for the classification of rheumatoid arthritis
      (RA) and from a large database of rheumatological patient charts developed for
      the CADIAG-II/RHEUMA system. An analysis of the relationships between RA and
      selected CADIAG-II/RHEUMA symptoms was done using two models. In one of them, we
      controlled for the differences in baseline frequencies of symptoms and diseases
      in the two study populations as an important factor influencing the results of
      the calculations. Other factors that were identified included inconsistent
      definitions of symptoms and diseases, and the different composition of study
      groups in the two study populations. By eliminating differences in baseline
      frequencies as the most important bias, the results obtained from the two
      different knowledge sources became more consistent. All remaining inconsistencies
      and uncertainties about the contribution and relative importance of the factors
      were formalized using fuzzy intervals.

PMID- 12069762
TI  - NasoNet, modeling the spread of nasopharyngeal cancer with networks of
      probabilistic events in discrete time.
AB  - The spread of cancer is a non-deterministic dynamic process. As a consequence,
      the design of an assistant system for the diagnosis and prognosis of the extent
      of a cancer should be based on a representation method that deals with both
      uncertainty and time. The ultimate goal is to know the stage of development of a
      cancer in a patient before selecting the appropriate treatment. A network of
      probabilistic events in discrete time (NPEDT) is a type of Bayesian network for
      temporal reasoning that models the causal mechanisms associated with the time
      evolution of a process. This paper describes NasoNet, a system that applies
      NPEDTs to the diagnosis and prognosis of nasopharyngeal cancer. We have made use
      of temporal noisy gates to model the dynamic causal interactions that take place
      in the domain. The methodology we describe is general enough to be applied to any
      other type of cancer.

PMID- 12069763
TI  - An evolutionary artificial neural networks approach for breast cancer diagnosis.
AB  - This paper presents an evolutionary artificial neural network (EANN) approach
      based on the pareto-differential evolution (PDE) algorithm augmented with local
      search for the prediction of breast cancer. The approach is named memetic pareto
      artificial neural network (MPANN). Artificial neural networks (ANNs) could be
      used to improve the work of medical practitioners in the diagnosis of breast
      cancer. Their abilities to approximate nonlinear functions and capture complex
      relationships in the data are instrumental abilities which could support the
      medical domain. We compare our results against an evolutionary programming
      approach and standard backpropagation (BP), and we show experimentally that MPANN
      has better generalization and much lower computational cost.

PMID- 12069764
TI  - Objective detection of brainstem auditory evoked potentials with a priori
      information from higher presentation levels.
AB  - This paper describes a brainstem auditory evoked potentials (BAEPs) detection
      method based on supervised pattern recognition. A previously used pattern
      recognition technique relying on cross-correlation with a template was modified
      in order to include a priori information allowing detection accuracy. Reference
      is made to the patient's audiogram and to the latency-intensity (LI) curve with
      respect to physiological mechanisms. Flexible and adaptive constraints are
      introduced in the optimization procedure by means of eight rules. Several data
      samples were used in this study. The determination of parameters was performed
      through 270 BAEPs from 20 subjects with normal and high audiometric thresholds
      and through additional BAEPs from 123 normal ears and 14 ears showing prominent
      wave VI BAEPs. The evaluation of the detection performance was performed in two
      steps: first, the sensitivity, specificity and accuracy were estimated using 283
      BAEPs from 20 subjects showing normal and high audiometric thresholds and
      secondly, the sensitivity, specificity and accuracy of the detection and the
      accuracy of the response threshold were estimated using 213 BAEPs from 18
      patients in clinic. Taking into account some a priori information, the accuracy
      in BAEPs detection was enhanced from 76 to 90%. The patient response thresholds
      were determined with a mean error of 5 dB and a standard deviation error of 8.3
      dB. Results were obtained using experimental data; therefore, they are promising
      for routine use in clinic.

PMID- 12069766
TI  - Piscirickettsiosis and piscirickettsiosis-like infections in fish: a review.
AB  - Piscirickettsia salmonis was the first "rickettsia-like" bacteria to be
      recognized as a pathogenic agent of fish. Since the first reports of
      piscirickettsiosis emerged from Chile in the late 1980s, Piscirickettsia-like
      bacteria have been recognized with increasing frequency in a variety of fish
      species, from both fresh and saltwaters around the world. Although the first
      reported incidents of Piscirickettsia were in salmonids, Piscirickettsia-like
      bacteria are now being frequently associated with disease syndromes in non
      salmonid fish. Mortalities have occurred in white seabass (Atactoscion noblis),
      black seabass (Dicentrarchus sp.), tilapia (Oreochromis, Tilapia and Sarotherodon
      spp.) and blue-eyed plecostomus (Panaque suttoni). Piscirickettsiosis and
      piscirickettsiosis-like diseases have affected aquaculture productivity,
      profitability, the species of fish compatible with commercial rearing, and
      transportation of fish from site to site. Piscirickettsiosis and syndromes caused
      by similar bacteria are an emerging disease complex that will increasingly
      inhibit fish production.

PMID- 12069767
TI  - Early interaction of canine calicivirus with cells is the major determinant for
      its cell tropism in vitro.
AB  - Canine calicivirus (CaCV) No. 48 strain isolated from a dog with fatal diarrhea
      is known to be able to replicate in MDCK and primary dog kidney cells. In this
      study, two new canine cell lines, MCM-B2 and MCA-B1, were determined to be
      permissive for CaCV No. 48, whereas other cell lines, including one canine cell
      line, A-72, were non-permissive. Flow cytometric analysis indicated that CaCV No.
      48 binds efficiently to the permissive cells and to some degree also to Vero
      cells that are non-permissive for the virus, but does not bind to the other non
      permissive cells tested. Both the permissive and non-permissive cells could be
      transfected with genomic RNA from CaCV No. 48, resulting in the appearance of
      CPE, production of capsid antigen and release of infectious progeny. These
      results suggested that the early interaction of the virus with cells, probably by
      binding to a virus receptor on the cell membrane, is the major determinant of
      CaCV No. 48 cell tropism in vitro.

PMID- 12069768
TI  - Detection of Shiga toxin-producing Escherichia coli by PCR in cattle in
      Argentina. Evaluation of two procedures.
AB  - Different experimental approaches were evaluated for their ability to detect stx
      genes by PCR and identify Shiga toxin-producing Escherichia coli (STEC) in bovine
      fecal samples. One hundred and sixty fecal samples from steers in Argentina were
      processed by protocols that involved: (1) enrichment of fecal samples and DNA
      extraction using a commercially available kit (Protocol A); (2) plating on
      selective media after enrichment of the fecal sample followed by heat-lysis DNA
      extraction from the confluent growth zone (Protocol B); (3) analysis of
      individual colonies isolated from direct fecal culture on MacConkey agar and
      sorbitol MacConkey agar supplemented with cefixime and potassium tellurite
      (Protocol C), used as Gold Standard. PCR performed on bacteria from the confluent
      growth zone (Protocol B) proved to be the most sensitive methodology. In
      addition, enrichment for greater than 6h, enhanced sensitivity. Among eight STEC
      isolates, four were O8:H19 and four were stx2/eae-negative. An STEC isolate was
      characterized as O26:H11 with a stx1/eae/EHEC-hlyA genotype, often associated
      with human disease. Finally, no STEC O157 strains were isolated using these
      methods.

PMID- 12069769
TI  - Pathogenesis of infections with Salmonella enterica subsp. enterica serovar
      Muenchen in the turtle Trachemys scripta scripta.
AB  - The pathogenesis of Salmonella enterica subsp. enterica serovar Muenchen
      infections in the aquatic turtle Trachemys scripta scripta was studied. After
      oral infection with 5x10(5)cfu of serovar Muenchen of 10-14-month-old turtles,
      kept at 26 degrees C, the intestine and especially the ileum, caecum and colon
      was colonized. Invasion of the intestinal wall, causing histopathological
      lesions, and colonization of internal organs were not observed. Serovar Muenchen
      was only isolated from turtles for 8 days after exposure. Keeping the turtles at
      37 degrees C caused colonization of liver and spleen in two of six orally
      infected turtles and augmented the numbers of bacteria in the intestinal tract.
      In contrast to oral infections, intraperitoneal infections of turtles with
      serovar Muenchen enabled the bacterium to persist inside the host for at least 5
      weeks. Clearance of serovar Muenchen from the liver and blood was more pronounced
      at 26 degrees C than at 37 degrees C. ELISA antibodies were demonstrated in
      intraperitoneally but not in orally infected turtles kept at 26 degrees C. In
      conclusion, the lack of persistence and invasiveness of serovar Muenchen in T. s.
      scripta after oral exposure might be due to the turtle's relatively low body
      temperature and/or the absence of well-organized gut-associated lymphoid tissue.

PMID- 12069770
TI  - Detection of Mycobacterium avium subsp. paratuberculosis by buoyant density
      centrifugation, sequence capture PCR and dot blot hybridisation.
AB  - Detection of Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) by
      polymerase chain reaction (PCR) is often hampered by the lack of efficient
      methods for sample treatment. We report a protocol for analysis of faecal samples
      based on buoyant density centrifugation in Percoll and IS900 sequence capture PCR
      combined with a dot blot assay for detection of low-grade infection of M.
      paratuberculosis. Serial dilutions of M. paratuberculosis genomic DNA and M.
      paratuberculosis bacteria were used to assess the sensitivity of the method. The
      final evaluation was performed with spiked faecal samples, which also were
      analysed by culture. The presence of PCR inhibitory substances in processed
      faecal samples was evaluated by including a PCR internal control. By using
      buoyant density centrifugation, sequence capture PCR, and dot blot hybridisation,
      we achieved a sensitivity of 10(3)CFU (colony forming units)/g of faeces. The
      detection limit by culture was assessed to 10(2)CFU/g of faeces. We conclude that
      the described protocol is a fast and sensitive alternative to bacterial culture
      of faecal samples.

PMID- 12069772
TI  - Isolation and characterization of Campylobacter, Helicobacter, and
      Anaerobiospirillum strains from a puppy with bloody diarrhea.
AB  - We carried out a microscopic examination of stools from a 2-month-old female
      puppy with bloody diarrhea, and this revealed large numbers of different spiral
      shaped bacteria. To isolate these organisms, a rectal swab specimen was
      inoculated onto plates of Skirrow's agar and incubated at 37 degrees C for 6 days
      in a microaerobic atmosphere. Finally, a total of six different spiral-shaped
      bacteria (strains G1104, 94105, FR106, B0101, 3J102, and J2103) were isolated.
      Based on their morphology, biochemical traits, whole-cell protein profiles, and
      analysis of their 16S rDNA sequences, they were identified as Campylobacter
      upsaliensis, Helicobacter cinaedi, 'Flexispira rappini', two Anaerobiospirillum
      spp. with different morphologies, and Helicobacter sp., respectively. Analysis of
      16S rRNA gene sequence data for strains 94150 (H. cinaedi) and FR106 (F. rappini)
      revealed that this approach has limitations when identifying isolates to the
      species level because of a high degree of sequence homology between these species
      (>99%) and considerable sequence variation among different isolates within these
      species. The dog was treated orally with amoxicillin for 3 days, which resolved
      the diarrhea. However, 1 day after the last dose the bloody diarrhea recurred but
      regarded to six more days amoxicillin treatment. This suggests a bacterial cause
      for the diarrhea. The approach to identification to microaerobic spiral-shaped
      bacteria in diarrheic dogs can be applied further to characterize their role in
      diarrhea illness.

PMID- 12069771
TI  - Shiga toxin genes in avian Escherichia coli.
AB  - The purpose of this study was to determine the presence of stx genes in avian
      pathogenic Escherichia coli (APEC). We examined 97 APEC isolates: 34 from lesions
      of avian cellulitis, 31 from avian septicemia, 13 from swollen head syndrome
      (SHS) in chickens, and 19 from diseased turkeys. We also examined five isolates
      from the feces of healthy chickens. All 102 E. coli isolates were tested for the
      presence of stx genes by PCR amplification and by colony blots using probes
      specific for stx1 and stx2. Fifty-three percent (52) of the 97 APEC carried stx
      gene sequences: one isolate carried stx2 sequences, two carried both stx1 and
      stx2 sequences, and the remaining 49 isolates carried only stx1 sequences. Twenty
      six isolates were positive by both hybridization and PCR amplification, 10 were
      positive by PCR only, and 16 were positive by hybridization only. All the stx
      positive isolates were negative by PCR for the eae and E-hlyA genes. The five
      isolates from healthy chickens were all negative for stx. All 13 SHS isolates
      were positive for the stx1 gene and had low titres for cytotoxicity in the Vero
      cell assay (VCA). Other stx-positive isolates were negative in the VCA. The stx1
      gene from one SHS E. coli isolate was cloned and sequenced and shown to be
      identical to that of the stx gene of Shigella dysenteriae. The observations
      indicate that stx1 gene sequences are widespread among APEC but that cytotoxicity
      on Vero cells is uncommon.

PMID- 12069773
TI  - Risk factors for repeat-breeder syndrome in New South Wales dairy cows.
AB  - A retrospective case-control study involving 1041 cow lactations from 10
      commercial dairy herds in Australia determined relationships between biographic,
      production, reproductive and disease factors and repeat-breeder syndrome (RBS)
      (conception to greater than two inseminations). The study population was
      stratified into primiparous- and multiparous-cow sub-groups and logistic
      regression was used. Effects of herd were examined by including this variable
      alternatively as a fixed and a random effect. In the primiparous-cow fixed-effect
      model, the risk of RBS was increased with post-calving metritis, stillbirth, and
      with increasing days taken to reach peak milk yield, and reduced following
      dystocia. An inverted U-shaped relationship with total milk-solids percentage at
      the time of first service was detected. In the multiparous-cow fixed-effect
      model, the risk of RBS was increased in cows with chronic metritis, cystic
      ovarian disease (COD), in cows of parity >5 and in cows that were sub-fertile in
      the previous lactation. Increasing days to first recorded heat (DFH) reduced risk
      of RBS and a non-linear relationship with average 120-day milk-protein percentage
      was found. When herd was fitted as a random effect, stillbirth and 120-day
      average milk-protein percentage were no longer significant in the primiparous and
      multiparous models, respectively. The study emphasises the need to control
      appropriately for the clustering effect of herd and supports the need to minimise
      periparturient disease and improve nutrient balance to achieve optimal fertility
      in dairy herds.

PMID- 12069774
TI  - Calculating sample size bounds for logistic regression.
AB  - The calculation of a study's required sample size is one of the most important
      aspects of the validity of an epidemiological study. Logistic regression often is
      used in modelling in epidemiology. A simplified method to calculate the sample
      size for the multiple logistic-regression model was proposed by Hsieh et al.
      [Stat. Med. 17 (1998) 1623]. The approach for estimating the sample size is
      described and then applied in the planning of an epidemiological cross-sectional
      study of the associations of different risk factors with Toxoplasma infection
      among pregnant women. Although the method demands some additional information
      which is often difficult to obtain, it is a very useful tool in veterinary
      epidemiology.

PMID- 12069775
TI  - The effect of claw trimming on the hoof health of Swedish dairy cattle.
AB  - A 2-year experiment on the effect of claw trimming on hoof health was performed
      in 77 Swedish dairy herds (3444 dairy cattle) selected on herd size, breed
      composition and membership in the official milk-recording scheme. In the autumn,
      cows within each herd were blocked according to breed, parity and stage of
      lactation and allocated to two treatments: autumn trimming (AT) or no autumn
      trimming (NAT). Outcome variables were claw measurements and prevalence of hoof
      lesions and lameness (measured at spring trimming) and the need for hoof
      treatments between scheduled trimmings. At spring trimming, NAT cows had longer
      and shallower claws than AT cows. The average net growth of the toe wall was
      greater for AT than for NAT cattle, with a marked variation between housing
      systems. Most hoof lesions present at AT had disappeared at the subsequent spring
      trimming. Controlled for clustering by herd-within-year and for the effects of
      individual-and herd-level covariates, AT cattle at spring trimmings had
      significantly lower odds of lameness (OR=0.66) and of haemorrhages of the sole or
      white-line (OR=0.86), sole ulcer (OR=0.59) and white-line fissure or double sole
      (OR=0.71)-but not of moderate-to-severe heel-horn erosion or dermatitis
      (OR=0.96). Acute hoof treatments between claw trimmings were more common in the
      NAT group (OR=2.02).

PMID- 12069776
TI  - Risk of introduction of BSE into Sweden by import of cattle from the United
      Kingdom.
AB  - All cattle of United Kingdom origin imported to Sweden since 1980 were traced
      (n=94) and the probability that none of these imported cattle had clinical signs
      of bovine spongiform encephalopathy (BSE) at the year of slaughter (death) was
      calculated. If BSE had been introduced by live-animal imports, the consequences
      of such an event also was evaluated. The potential of the recently introduced
      surveillance system of high-risk cattle to detect such an event also was
      evaluated. We found that BSE most probably has not been introduced to Sweden by
      live-animal imports. We also found that, if this event had occurred and assuming
      a worst-case scenario that the animal was not prevented from being rendered, the
      rendering system (during certain periods) would not have prevented further spread
      of infection. Finally, we found that the BSE surveillance of high-risk cattle has
      not been in place long enough to verify that this event has not occurred (as of
      December 2001).

PMID- 12069778
TI  - Risk factors for clinical Salmonella enterica subsp. enterica serovar Typhimurium
      infection on Dutch dairy farms.
AB  - Risk factors for outbreaks in 1999 of clinical Salmonella enterica subsp.
      enterica serovar Typhimurium infection on dairy farms were studied in a matched
      case-control study with 47 case farms and 47 control farms. All 47 case farms
      experienced a clinical outbreak of salmonellosis which was confirmed with a
      positive bacteriologic culture for serovar Typhimurium in one or more samples.
      Serovar Typhimurium phage type 401 and 506 (definitive type 104, DT104) were the
      most frequently isolated phage types (13 isolates). On most farms (66%), clinical
      signs were seen only among adult cows. The most frequently reported clinical
      signs were diarrhoea (in 92% of the farms) and depression (in 79% of the farms).
      Control farms were matched on region and had no history of salmonellosis. A
      questionnaire was used to collect data on case and control farms. The
      relationship between serovar Typhimurium status of the farm and possible risk
      factors was tested using conditional logistic regression. Significant factors in
      the final model were presence of cats on the farm (OR=0.06), purchase of manure
      (OR=21.5), feeding colostrum only from own dam (OR=0.08), a non-seasonal calving
      pattern (OR=25), unrestricted grazing of lactating cows (OR=0.07), and a high
      mean mowing percentage of pasture (OR=1.02).

PMID- 12069779
TI  - Prevalence of and risk factors for Salmonella in water offered to weaned dairy
      calves in California, USA.
AB  - Water from troughs used by weaned dairy calves was sampled on California, USA
      dairies to determine the prevalence and associated risk factors for Salmonella
      contamination. Salmonella were found on 4 of 48 dairies (4/82 water samples) in
      fall 1998 and on 8 of the same 37 dairies (8/83 water samples) in summer, 1999.
      Serotypes isolated from the water were Salmonella meleagridis and Salmonella
      typhimurium. Primary risk factors associated with the increased prevalence of
      Salmonella in water offered to weaned dairy calves were a continuous water tank
      filling method compared to a valve (an "on-demand" procedure) and a water pH>8.

PMID- 12069777
TI  - Molecular epidemiology of feline bordetellosis in two animal shelters in
      California, USA.
AB  - "Kennel cough" in dogs in animal shelters is readily transmissible, reduces
      adoption rates, and commonly leads to the euthanasia of affected dogs. In cats,
      tracheobronchitis, conjunctivitis, and pneumonia have been associated with
      Bordetella bronchiseptica infection-but most cases of upper-respiratory infection
      (URI) probably are caused by herpesvirus and calicivirus, and many B.
      bronchiseptica culture-positive cats are clinically normal. Our prospective
      observational study was undertaken to document the contribution of B.
      bronchiseptica to disease in cats and dogs from two animal shelters undergoing
      outbreaks of canine kennel cough, to evaluate whether cross-species transmission
      might have occurred, and to determine if the presence of infected cats
      represented a risk to dogs. Clinically defined cases of kennel cough in dogs and
      URI in cats were investigated in two shelters by calculating clinical-disease
      incidence, alveolar-lavage cytological examination, bacterial and viral cultures,
      antibiotic-susceptibility testing, and molecular fingerprinting by pulsed-field
      gel electrophoresis. In a 40-cat and 40-dog "no-kill" shelter, the prevalences of
      culture positivity were 47% for B. bronchiseptica and 36% for calicivirus at the
      same time as two resident dogs demonstrated clinical cough. When no dogs had
      kennel cough 3 months later, 10% of cats were B. bronchiseptica-culture-positive
      and 63% calicivirus positive. In a large traditional shelter, the incidence of
      kennel cough in dogs increased over 12 weeks to a maximum of 19 cases/week/120
      dogs, during which time the culture prevalence was 23% for B. bronchiseptica in
      dogs and 47% in cats. Three to 6 months before the kennel-cough epidemic, no dogs
      or cats were B. bronchiseptica positive. Very little genetic variability was
      detected in isolates from these shelters; all isolates except one corresponded to
      a single strain type which was identical to the pattern in a vaccine used in
      these shelters. Isolates from other cats, a horse, a llama, and a sea otter were
      genetically distinct from the shelter isolates. There was widespread resistance
      to cephalosporins and ampicillin, but low or no resistance to
      amoxicillin/clavulanate, trimethoprim-sulfamethoxazole, tetracycline, and
      enrofloxacin. Greater percent resistance was observed in the traditional shelter
      than in the no-kill shelter and feline isolates were more likely to be resistant
      than canine isolates.

PMID- 12069780
TI  - Risk factors for metritis in Danish dairy cows.
AB  - A retrospective longitudinal study of metritis was conducted in Denmark on data
      collected during 1993-1994. Data on herd size, breed, parity, and treatment of
      disease were obtained from the Danish Cattle Database. Management and production
      facility data were collected using a questionnaire, conducted as a telephone
      interview in 1994. The study included 2144 herds from three regions in Denmark
      (102,060 cows). Herd-level variables included were: herd size, housing, flooring,
      grazing, calving measures, and calving supervision. Cow-level variables were:
      parity, breed, calving season and whether the cow had been treated by a
      veterinarian for dystocia or the diseases: retained placenta, reproductive
      disease, ketosis, milk fever, or dry cow mastitis. Marginal multivariable
      logistic-regression analyses were performed. The cow with highest odds of
      metritis was a first or greater than or equal to third parity cow, of large
      breed, that calved during November-April, in a zero-grazing herd. The cow had
      been treated for dystocia, retained placenta, and at least one other reproductive
      disease, but not for ketosis.

PMID- 12069781
TI  - Diacylglyceride kinases, sphingosine kinases and NAD kinases: distant relatives
      of 6-phosphofructokinases.
AB  - Diacylglyceride kinases, sphingosine kinases, NAD kinases and 6
      phosphofructokinases are thought to be related despite large evolution of their
      sequences. Discovery of a common signature has led to the suggestion that they
      possess a similar phosphate-donor-binding site and a similar phosphorylation
      mechanism. The substrate- and allosteric-binding sites are much more divergent
      and their delineation remains to be determined experimentally.

PMID- 12069787
TI  - Anxiety over GABA(A) receptor structure relieved by AChBP.
AB  - The GABA(A) receptor is the primary mediator of inhibitory neurotransmission in
      the brain and is a major target for neuromodulatory drugs such as
      benzodiazepines, barbiturates, ethanol and anaesthetics. However, our
      understanding of the molecular details of this receptor has been limited by a
      lack of high-resolution structural information. This article presents a new model
      for the extracellular, ligand-binding domain of the GABA(A) receptor, that is
      based on the recently determined structure of a soluble acetylcholine-binding
      protein. The model puts existing mutational and biochemical data into a three
      dimensional context, shows details of the GABA- and benzodiazepine-binding sites,
      and highlights the importance of other regions in allosteric conformational
      change. This provides a new perspective on existing data and an exciting new
      framework for understanding this important family of receptors.

PMID- 12069788
TI  - A new spin on protein dynamics.
AB  - Site-directed spin labeling is a general method for investigating structure and
      conformational switching in soluble and membrane proteins. It will also be an
      important tool for exploring protein backbone dynamics. A semi-empirical analysis
      of nitroxide sidechain dynamics in spin-labeled proteins reveals contributions
      from fluctuations in backbone dihedral angles and rigid-body (collective) motions
      of alpha helices. Quantitative analysis of sidechain dynamics is sometimes
      possible, and contributions from backbone modes can be expressed in terms of
      relative order parameters and rates. Dynamic sequences identified by site
      directed spin labeling correlate with functional domains, and so nitroxide
      scanning could provide an efficient strategy for identifying such domains in high
      molecular weight proteins, supramolecular complexes and membrane proteins.

PMID- 12069789
TI  - Development of protein-detecting microarrays and related devices.
AB  - There is great interest in the development of devices capable of monitoring the
      levels and post-translational modification states of hundreds or thousands of
      proteins simultaneously. One way to do this would be to create protein-detecting
      microarrays roughly akin to the DNA microarrays that are used for genome-wide
      expression studies. Two major challenges must be addressed before practical
      devices of this type become available. One is the development of high-throughput
      methods for the isolation of protein-binding compounds that will act as capture
      molecules in the array. The second is the optimization of methods that register
      binding of target proteins to the immobilized ligands in a sensitive and
      quantitative fashion. Progress in these areas, and some of the challenges
      remaining, are reviewed in this article.

PMID- 12069790
TI  - Mammalian prion proteins: enigma, variation and vaccination.
AB  - Although misfolding of the cellular prion protein PrP(C) into an alternative
      form, denoted PrP(Sc), is a key event in prion infections, the normal function of
      PrP(C) remains to be clearly defined. Many PrP(C)-binding proteins have been
      identified, but authentication of these interactions in functional assays is
      incomplete. Doppel (Dpl), a recently discovered PrP-like protein, might provide a
      new avenue by which to explore physiological and pathological functions of PrP.
      For example, overexpression of Dpl causes apoptotic cerebellar cell death that is
      abrogated by PrP(C), indicating that these two proteins can act in a common
      pathway. Despite our incomplete understanding of PrP(C), immunological targeting
      of this PrP(Sc) precursor has produced encouraging results, indicating a
      potential point of intervention against these fatal diseases.

PMID- 12069791
TI  - Cellular hijacking: a common strategy for microbial infection.
AB  - Eukaryotic cells are under constant attack from microbial intruders seeking a
      selective advantage for survival, propagation and dissemination. Microbial
      infections can often result in disease and might even be lethal to the host if
      they are not combatted effectively. Studies of host-pathogen interactions have
      revealed that virulence often requires the usurpation of existing cell signaling
      pathways or membrane traffic machinery of the host. Such studies provide a rich
      source of cell biological data that will probably prove essential for future
      efforts designed to either thwart these attacks or learn from them.

PMID- 12069796
TI  - Abstracts of the 51st International Congress of the European Society for
      Cardiovascular Surgery. June 29-July 1, 2002. Helsinki, Finland.

PMID- 12069792
TI  - Predicting functional divergence in protein evolution by site-specific rate
      shifts.
AB  - Most modern tools that analyze protein evolution allow individual sites to mutate
      at constant rates over the history of the protein family. However, Walter Fitch
      observed in the 1970s that, if a protein changes its function, the mutability of
      individual sites might also change. This observation is captured in the "non
      homogeneous gamma model", which extracts functional information from gene
      families by examining the different rates at which individual sites evolve. This
      model has recently been coupled with structural and molecular biology to identify
      sites that are likely to be involved in changing function within the gene family.
      Applying this to multiple gene families highlights the widespread divergence of
      functional behavior among proteins to generate paralogs and orthologs.

PMID- 12069804
TI  - Biological functions of a novel lipid mediator, cyclic phosphatidic acid.
AB  - A novel bioactive lipid, cyclic phosphatidic acid (cPA), was isolated originally
      from myxoamoebae of a true slime mold, Physarum polycephalum, and has now been
      detected in a wide range of organisms from slime molds to humans. It has a cyclic
      phosphate at the sn-2 and sn-3 positions of the glycerol carbons, and this
      structure is absolutely necessary for its activities. This substance shows
      specific biological functions, including antimitogenic regulation of the cell
      cycle, regulation of actin stress fiber formation and rearrangement, inhibition
      of cancer cell invasion and metastasis, regulation of differentiation and
      viability of neuronal cells, and mobilization of intracellular calcium. Although
      the structure of cPA is similar to that of lysophosphatidic acid (LPA), its
      biological activities are apparently distinct from those of LPA. In the present
      review, we focus mainly on the enzymatic formation of cPA, the antimitogenic
      regulation of the cell cycle, the inhibition of cancer cell invasion and
      metastasis, and the neurotrophic effect of cPA.

PMID- 12069805
TI  - Sphingosine-1-phosphate and lipid phosphohydrolases.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts as both an
      extracellular ligand for the endothelial differentiation gene-1 (EDG-1) G-protein
      coupled receptor (GPCR) family and as an intracellular messenger. Cellular levels
      of S1P are low and tightly regulated in a spatial-temporal manner not only by
      sphingosine kinase (SPHK) but also by degradation catalyzed by S1P lyase,
      specific S1P phosphohydrolases, and by general lipid phosphate phosphohydrolases
      (LPPs). LPPs are characterized as magnesium-independent, insensitive to
      inhibition by N-ethylmaleimide (NEM) and possessing broad substrate specificity
      with a variety of phosphorylated lipids, including S1P, phosphatidic acid (PA),
      and lysophosphatidic acid (LPA). LPPs contain three highly conserved domains that
      define a phosphohydrolase superfamily. Recently, several specific S1P
      phosphohydrolases have been identified in yeast and mammalian cells. Phylogenetic
      and biochemical analyses indicate that these enzymes constitute a new subset of
      the LPP family. As further evidence, S1P phosphohydrolases exhibit high
      specificity for phosphorylated sphingoid bases. Enforced expression of S1P
      phosphohydrolase alters the cellular levels of sphingolipid metabolites in yeast
      and mammalian cells, increasing sphingosine and ceramide, bioactive sphingolipids
      that often have opposing biological actions to S1P. By regulating the cellular
      ratio between ceramide/sphingosine and S1P, S1P phosphohydrolase is poised to be
      a critical factor in cell survival/cell death decisions. Indeed, expression of
      S1P phosphohydrolase in mammalian cells increases apoptosis, whereas deletion of
      S1P phosphohydrolases in yeast correlates with resistance to heat stress. In this
      review, we discuss the role of phosphohydrolases in the metabolism of S1P and how
      turnover of S1P can regulate sphingolipid metabolites signaling.

PMID- 12069806
TI  - Physiological and pathophysiological roles of lysophosphatidic acids produced by
      secretory lysophospholipase D in body fluids.
AB  - Recently, a family of phospholipid mediators has received much attention because
      of its variety of biological activities. Lysophosphatidic acid (LPA) is a central
      member of the phospholipid autacoid family that exerts diverse effects through
      binding to and activation of several specific receptors coupled to G-proteins. In
      accordance with its function as a receptor agonist, there are pathways for
      extracellular generation of LPA in vivo. One pathway involves a novel
      lysophospholipase D activity that was originally found in rat plasma. LPA is also
      produced in significant amounts after incubation of various plasma-derived body
      fluids such as human follicular fluid at 25-37 degrees C. In animal models, LPA
      was shown to stimulate oocyte maturation, embryonic development and transport in
      the oviduct. An increase in serum lysophospholipase D activity was observed
      during pregnancy in human. These results suggest that LPA generated by
      lysophospholipase D is likely to play an important role in reproductive biology.
      LPA produced by lysophospholipase D activity in body fluids has also been
      observed under pathophysiological conditions: serum and ascitic fluid from
      ovarian cancer patients and serum from hypercholesterolemic rabbits. Hence,
      excess generation of LPA by lysophospholipase D activity in body fluids has been
      suggested to be relevant to the pathogenesis of cancer and atherosclerosis.

PMID- 12069807
TI  - Structure and function of phosphatidylserine-specific phospholipase A1.
AB  - Phospholipase A1 (PLA1) is an enzyme that hydrolyzes the sn-1 fatty acids from
      phospholipids and produces 2-acyl-lysophospholipids. Although PLA1 activities are
      detected in many tissues and cell lines, a limited number of PLA1s have been
      purified and cloned so far. These include phosphatidylserine (PS)-specific PLA1
      (PS-PLA1) from rat platelets, PLA1 from vespid venom, and phosphatidic acid (PA)
      preferential PLA1 (PA-PLA1). Structurally, the former two PLA1s belong to the
      lipase family, where they form a subfamily among the lipase family. An alignment
      of the PLA1s with other members of the lipase family revealed two molecular
      characteristics of PLA1: the presence of extremely short lids and deleted beta9
      loops. The two surface loops have been implicated in the ligand recognition in
      human pancreatic lipase (PL) and guinea pig PL-related protein 2. Under
      physiological conditions, accessibility of PS-PLA1 to its substrate is limited as
      it is a secreted enzyme and PS is normally located in the inner leaflet of the
      lipid bilayer. However, PS-PLA1 efficiently hydrolyzes PS exposed on the surface
      of cells such as apoptotic cells and activated platelets, and produces 2-acyl
      lysophosphatidylserine (lysoPS), which is a lipid mediator for mast cells, T
      cells and neural cells. Identification of PS-PLA1 reveals the presence of PLA1
      subfamily within the lipase family and suggests that PLA1 has a role in the
      production of lysophospholipid mediators.

PMID- 12069808
TI  - Lipid phosphate phosphatases regulate signal transduction through glycerolipids
      and sphingolipids.
AB  - Lipid phosphate esters including lysophosphatidate (LPA), phosphatidate (PA),
      sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P) are bioactive in
      mammalian cells and serve as mediators of signal transduction. LPA and S1P are
      present in biological fluids and activate cells through stimulation of their
      respective G-protein-coupled receptors, LPA(1-3) and S1P(1-5). LPA stimulates
      fibroblast division and is important in wound repair. It is also active in
      maintaining the growth of ovarian cancers. S1P stimulates chemotaxis,
      proliferation and differentiation of vascular endothelial and smooth muscle cells
      and is an important participant in the angiogenic response and neovessel
      maturation. PA and C1P are believed to act primarily inside the cell where they
      facilitate vesicle transport. The lipid phosphates are substrates for a family of
      lipid phosphate phosphatases (LPPs) that dramatically alter the signaling balance
      between the phosphate esters and their dephosphorylated products. In the case of
      PA, S1P and C1P, the products are diacylglycerol (DAG), sphingosine and ceramide,
      respectively. These latter lipids are also bioactive and, thus, the LPPs change
      signals that the cell receives. The LPPs are integral membrane proteins that act
      both inside and outside the cell. The "ecto-activity" of the LPPs regulates the
      circulating and locally effective concentrations of LPA and S1P. Conversely, the
      internal activity controls the relative accumulation of PA or C1P in response to
      stimulation by various agonists thereby affecting cell signaling downstream of
      EDG and other receptors. This article will review the various LPPs and discuss
      how these enzymes could regulate signal transduction by lipid mediators.

PMID- 12069810
TI  - Biological activities and metabolism of the lysophosphoinositides and
      glycerophosphoinositols.
AB  - The lysophospholipids are integral components of the plasma membrane that have
      often been considered as side products of the phospholipase A2 (PLA2)-dependent
      production of arachidonic acid and the deacylation/reacylation processes involved
      in phospholipid homeostasis. Data indicating roles of these lipid derivatives in
      hormone responses and cell transformation have now led to a different view, and
      the understanding of their involvement in the modulation of cell function is
      building up. Here, we will summarise the current knowledge concerning the
      biological roles of the lysophosphoinositides and the glycerophosphoinositols
      (their fully deacylated counterparts) in the framework of their known effects,
      and those of the other lysophospholipids and glycerophospholipids.

PMID- 12069809
TI  - Roles for lipid phosphate phosphatases in regulation of cellular signaling.
AB  - Lipid phosphate phosphatases (LPPs) are a family of integral membrane
      glycoproteins that catalyze the dephosphorylation of a number of bioactive lipid
      mediators including lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P)
      and phosphatidic acid (PA). These mediators exert complex effects on cell
      function through both actions at cell surface receptors and on intracellular
      targets. The LPP-catalyzed dephosphorylation of these substrates can both
      terminate their signaling actions and itself generate further molecules with
      biological activity. Recent advances have revealed that a family of structurally
      related genes is responsible for LPP activities in species from yeast to mammals.
      These genes exhibit distinct but overlapping expression patterns and their
      products appear to be heterogeneous with respect to their posttranslational
      modification and subcellular localizations. Here we review the structure and
      catalytic properties of the LPPs and consider recent developments in
      understanding their cellular biology and functions.

PMID- 12069811
TI  - Lysophospholipid receptor nomenclature.

PMID- 12069812
TI  - Signaling of sphingosine-1-phosphate via the S1P/EDG-family of G-protein-coupled
      receptors.
AB  - The sphingosine-1-phosphate/Endothelial Differentiation Gene (S1P/EDG) family of
      G-protein-coupled receptors (GPCR) currently includes five different isoforms,
      which differentially regulate fundamental cellular processes such as migration,
      proliferation, cytoskeletal organization, adherens junction assembly and
      morphogenesis. Additionally, specific S1P/EDG isoforms can regulate important
      physiological processes such as blood vessel maturation, cardiac development and
      angiogenesis in vivo. Herein, we review the current state of knowledge of the
      expression patterns, signaling pathways and functional characteristics of the
      different S1P receptors. Further investigation in this field will likely improve
      our understanding of cardiovascular development as well as vascular diseases and
      may lead to novel therapeutic approaches.

PMID- 12069813
TI  - Sphingosylphosphorylcholine and lysophosphatidylcholine: G protein-coupled
      receptors and receptor-mediated signal transduction.
AB  - In recent years, certain lysophospholipids (lyso-PLs) have been recognized as
      important cell signaling molecules. Among them, two phosphorylcholine-containing
      lyso-PLs, sphingosylphosphorylcholine (SPC) and lysophosphatidylcholine (LPC),
      have been shown to be involved in many cellular processes and are produced under
      physiological and pathological conditions. Although signaling properties of SPC
      and LPC have been studied in a variety of cellular systems, specific cell
      membrane receptors for SPC and LPC have not been identified previously. Recently,
      ovarian cancer G protein-coupled receptor 1 (OGR1, also known as GPR68), G
      protein-coupled receptor 4 (GPR4), and G2A have been identified as receptors for
      SPC and LPC. The signaling and ligand-binding properties of these receptors are
      reviewed here. These discoveries provide an intriguing opportunity and a novel
      approach in studying the pathophysiological roles of SPC and LPC and their
      receptors.

PMID- 12069814
TI  - Homodimerization and heterodimerization of S1P/EDG sphingosine-1-phosphate
      receptors.
AB  - Sphingosine-1-phosphate (S1P) binds to and signals through several members of a
      group of G protein-coupled receptors (GPCRs) known as the S1P/EDG family. Several
      of these receptors are coexpressed in various cell types and recent reports have
      shown that biological effects of S1P often require more than one S1P receptor
      subtype. Recent evidence indicates that many GPCRs exist as dimers. We show that
      S1P receptors form both homodimers as well as heterodimers with other members of
      the S1P subfamily of receptors. We also discuss the role that GPCR dimers play in
      receptor function and what this may mean for S1P signaling.

PMID- 12069815
TI  - Pathways of transduction engaged by sphingosine 1-phosphate through G protein
      coupled receptors.
AB  - Pathways of transduction employed by receptors for sphingosine 1-phosphate (S1P)
      are identified by the nature of second messengers and/or downstream targets
      regulated and, more formally, by direct assays of heterotrimeric G protein
      activation. The different methods generally agree. S1P1 couples to members of the
      Gi family, apparently selectively, although reported pertussis toxin (PTX)
      insensitive actions make categorical statements regarding exclusivity difficult.
      S1P2 and S1P3 couple to members of the Gi, Gq, and G12/13 families. S1P4 couples
      to Gi and possibly G12/13, while S1P5 couples to Gi and G12/13 but not to Gq. In
      virtually all circumstances, coupling of S1P receptors to Gi is reflected in PTX
      sensitive inhibition of adenylyl cyclase, activation of extracellular-regulated
      kinases (ERKs), and, depending on the cell, activation of phospholipase C (PLC).
      Coupling to Gq is reflected in PTX-insensitive activation of phospholipase C.
      Coupling to G12/13 is reflected in activation of Rho and subsequent activation of
      serum response factor (SRF). Specific linkages have been verified in almost all
      instances by receptor-promoted [35S]GTPgammaS/GDP exchange on identified G
      proteins.

PMID- 12069816
TI  - Trans-regulation of epidermal growth factor receptor by lysophosphatidic acid and
      G protein-coupled receptors.
AB  - Lysophosphatidic acid (LPA) is known to induce protein tyrosine phosphorylation
      and has growth factor-like effects. In the last several years, the epidermal
      growth factor (EGF) receptor has been recognized as a protein tyrosine kinase
      that plays a central role in mediating LPA-induced tyrosine phosphorylation and
      Erk MAP kinase activation. In this article, we review recent progress in the
      study of trans-regulation of EGF receptor by LPA and G protein-coupled receptors
      (GPCR) and discuss the gap in our knowledge of the mechanism by which LPA induces
      EGF receptor activation.

PMID- 12069817
TI  - Phosphoinositide 3-kinases in lysophosphatidic acid signaling: regulation and
      cross-talk with the Ras/mitogen-activated protein kinase pathway.
AB  - Recent reports have shown that phosphoinositide 3-kinases (PI3Ks) mediate various
      biological activities of lysophosphatidic acid (LPA), including cell
      proliferation or survival. In addition, these enzymes have been proposed to be
      early intermediates of mitogen-activated protein kinase (MAPK) activation. Here
      we summarize our current knowledge of the mechanisms underlying these
      observations. p110gamma is an isoform of PI3K that can be activated in vitro by
      Gbetagamma subunits and was therefore considered as the logical candidate to
      mediate responses induced by G protein-coupled receptor (GPCR) agonists. In
      agreement with this, p110gamma has been involved in different biochemical models
      linking Gbetagamma to MAPK activation. Nevertheless, its apparent tissue-specific
      distribution has raised questions regarding the physiological relevance of these
      models. In addition, LPA can activate p110beta, a member of the phosphotyrosine
      dependent PI3K subfamily that participates in the mitogenic effect of LPA. Its
      activation is thought to involve a synergistic effect of Gbetagamma and
      phosphotyrosine motifs provided by a transactivated EGF receptor/Gab1 pathway. We
      are currently studying a possible role of p110beta upstream from Ras, suggesting
      that this protein could provide a novel connection between betagamma and the MAPK
      pathway.

PMID- 12069818
TI  - Subtype-specific differential regulation of Rho family G proteins and cell
      migration by the Edg family sphingosine-1-phosphate receptors.
AB  - One of the striking activities of the Edg family sphingosine-1-phosphate (S1P)
      receptors includes receptor isotype-specific, bimodal regulatory activity on cell
      migration. While Edg1 and Edg3 act as typical chemotactic receptors, Edg5
      uniquely acts as a chemorepellant receptor. Consistent with this, Edg1 and Edg3,
      and Edg5 regulate the activity of the Rho family GTPase Rac positively and
      negatively, respectively. Thus, Edg isotype-specific, differential regulatory
      activities on Rac seem to be important as mechanisms underlying the bimodal
      regulation of cell migration by S1P. Edg5-mediated Rac inhibition involves
      stimulation of Rac-GTPase-activating protein (GAP) activity, rather than
      inhibition of Rac-guanine nucleotide exchange factor (GEF) activity. Many cell
      types including vascular smooth muscle and endothelial cells express more than a
      single S1P receptor isotype. In these cells, it appears that an integration of
      the Edg isotype-selective, positive and negative signals on cellular Rac activity
      is a critical determinant for eventual direction of regulation on cell motility
      by S1P. Physiological and pathological roles for the repulsive activity of Edg5
      receptor remain to be clarified.

PMID- 12069819
TI  - Sphingosine 1-phosphate signalling and termination at lipid phosphate receptors.
AB  - Sphingosine 1-phosphate (S1P) is a polar lysophospholipid metabolite that is
      stored in platelets and released upon their activation. However, diverse stimuli
      such as growth factors, cytokines, G-protein coupled receptor (GPCR) agonists and
      antigens have been shown to increase sphingosine kinase activity and S1P
      formation in other cell types, such as smooth muscle. Indeed, S1P has been
      implicated in the regulation of several important cellular processes, such as
      proliferation, differentiation, apoptosis and migration in these cells. Over the
      past few years, there has been a major advance in our understanding of how S1P
      can act as an intercellular mediator by binding to a new class of G-protein
      coupled receptors to regulate cell function. This review focuses on the enzymatic
      regulation of S1P formation and degradation and its interaction with a novel
      tethered receptor complex containing the S1P receptor (S1P(1)) and the platelet
      derived growth factor (PDGF) beta receptor. This tethered receptor complex
      enables coincident integrative signalling to p42/p44 MAPK. This is compared with
      a sequential model in which PDGF promotes S1P release, which in turn acts on
      S1P(1) to promote Rac signalling.

PMID- 12069820
TI  - Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate:
      is this an atherogenic mediator or an anti-atherogenic mediator?
AB  - Sphingosine 1-phosphate (S1P) concentration in plasma and serum has been
      estimated to be within 200-900 nM. Among plasma and serum components, S1P is
      concentrated in lipoprotein fractions with a rank order of high-density
      lipoprotein (HDL)>low-density lipoprotein (LDL)>very low-density lipoprotein
      (VLDL)>lipoprotein-deficient plasma (LPDP) when expressed as the per unit amount
      of protein. It is well known that LDL, especially oxidized LDL, is closely
      correlated and HDL is inversely correlated, with the risk of cardiovascular
      disease, such as atherosclerosis. Evidence was presented that a part of HDL
      induced actions previously reported are mediated by the lipoprotein-associated
      S1P. Furthermore, S1P content in LDL was markedly decreased during its oxidation.
      This paper will discuss whether S1P is an atherogenic mediator or an anti
      atherogenic mediator.

PMID- 12069821
TI  - Sphingolipids involved in the induction of multinuclear cell formation.
AB  - In this review, we focus on sphingolipids as potential regulators of the
      induction of multinuclear cell formation through the inhibition of cytokinesis. A
      sphingolipid, psychosine (Psy) (galactosylsphingosine), was demonstrated to be a
      trigger lipid for the inhibition of cytokinesis and the induction of multinuclear
      giant cells associated with a sphingolipid metabolic disease, globoid cell
      leukodystrophy (GLD). Indeed, Psy is known to accumulate in the patients' brains.
      Interestingly, inhibition of sphingolipid biosynthesis also induced multinuclear
      cells. When cells were treated with a new immunosuppressant, ISP-1/myriocin,
      which inhibits serine palmitoyltransferase, the first step enzyme of sphingolipid
      biosynthesis, the cells underwent multinucleation and apoptosis. At present, a
      definitive model of the function of sphingolipids as to the induction of
      multinuclear cell formation is not available due to the rudimentary information
      but possible mechanisms are discussed.

PMID- 12069822
TI  - Regulation of neuronal cytoskeleton by lysophosphatidic acid: role of GSK-3.
AB  - Neurite retraction is a crucial process during nervous system development and
      neurodegeneration. This process implies reorganization of the neuronal
      cytoskeleton. Some bioactive lipids such as lysophosphatidic acid (LPA) induce
      neurite retraction. The reorganization of the actin cytoskeleton during neurite
      retraction is one of the best-characterized effects of LPA. However, less
      information is available regarding the reorganization of the microtubule (MT)
      network in response to LPA in neuronal cells. Here, we first give an overview of
      the roles of cytoskeleton during neurite outgrowth, and subsequently, we review
      some of the data from different laboratories concerning LPA-induced cytoskeletal
      rearrangement in neuronal cells. We also summarize our own recent results about
      modifications of MTs during LPA-induced neurite retraction. We have shown that
      LPA induces changes in tubulin pools and increases in the phosphorylation levels
      of microtubule-associated proteins (MAPs), such as Tau. Tau hyperphosphorylation
      in response to LPA is mediated by the activation of glycogen synthase kinase-3
      (GSK-3). The upregulation of GSK-3 activity by LPA seems to be a general process
      as it occurs in diverse neuronal cells of different species in correlation with
      the neurite retraction process.

PMID- 12069823
TI  - Multiple astrocyte responses to lysophosphatidic acids.
AB  - Lysophosphatidic acid (LPA) and LPA receptors are enriched in the brain.
      Moreover, the levels of these receptors and ligand are modulated during brain
      development and injury, respectively, suggesting multiple roles for LPA in the
      brain. In cultured astrocytes and glioma-derived cells, LPA increases
      intracellular calcium concentrations and causes morphological changes. LPA also
      induces glioma cell migration. In normal astrocytes, LPA stimulates reactive
      oxygen species synthesis, activation of multiple protein kinases and expression
      of c-fos and c-jun. It is noteworthy that LPA-induced astrocyte responses vary as
      a function of the specific brain region of origin of the astrocytes. This may be
      one factor in the finding of LPA-stimulated proliferation in some, but not all,
      astrocyte studies. The species and/or developmental stage also differed in many
      of the astrocyte proliferation analyses. Micromolar LPA is required to elicit
      some astrocyte responses, including the stimulation of cytokine expression and
      inhibition of glutamate uptake. These events could significantly impact on
      survival of injured neurons and micromolar LPA concentrations are likely in
      diverse brain pathologies. There are important aspects of astrocyte LPA responses
      still to be fully evaluated, including functions in development and activation,
      synergy between LPA and other biomediators, and astrocyte interactions with other
      cells.

PMID- 12069824
TI  - Lysophospholipid mediators of immunity and neoplasia.
AB  - Lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and some other
      structurally related lysophospholipids are active growth factors and stimuli for
      diverse cellular functions. LPA and S1P promote early T cell migration to tissue
      sites of immune responses and regulate T cell proliferation and secretion of
      numerous cytokines. Edg-4 (LPA2) LPA receptors, which are constitutively
      expressed by helper T cells, and Edg-2 (LPA1) LPA receptors, which are expressed
      only by activated helper T cells, transduce opposite effects of LPA on some T
      cell responses. A similar mechanism is observed for fine regulation of Edg R
      mediated effects of LPA on ovarian cancer cells. Edg-4 (LPA2) R transduces
      proliferative responses, recruitment of autocrine protein growth factors, and
      migration of ovarian cancer cells, whereas Edg-2 (LPA1) R transduces inhibition
      of Edg-4 (LPA2) R-mediated responses and concurrently elicits apoptosis and
      anoikis of ovarian cancer cells. Edg-4 (LPA2) R is a distinctive functional
      marker for ovarian carcinoma, and is expressed both as the wild-type and a
      carboxyl-terminally extended gain-of-function mutant. Newly discovered non-lipid
      agonists and antagonists for individual Edg receptors will permit more
      sophisticated analyses of their respective contributions in human biology and
      pathophysiology, and may represent novel therapeutic modalities in immune
      disorders and cancer.

PMID- 12069825
TI  - Lysophospholipids and their G protein-coupled receptors in inflammation and
      immunity.
AB  - Among the family of lipid-derived mediators, the group of lysophospholipids
      including lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) have
      growth-related and -unrelated effects on diverse cell types including
      lymphocytes, macrophages, smooth muscle cells, endothelial cells, and neuronal
      cells. This review summarizes the known effects of lysophospholipids and their G
      protein-coupled receptors (GPCRs) in inflammation and immunity. Lysophospholipids
      have the capacity to evoke and modulate immune responses by attracting and
      activating T-cells, B-cells and macrophages directly and influencing their
      interactions with other cell types. Immune cells express multiple subsets of
      lysophospholipid receptors, which are critical for specific cellular responses
      such as proliferation and migration that are fundamental to immunity.
      Investigation of the expression pattern of EDG-receptors on human T-cells
      revealed a dynamic transcriptional regulation influenced by both developmental
      stages and activation states. Other lipid mediators like psychosine and other
      GPCRs for lipid mediators like G2A also may be involved in the development of
      normal immune and inflammatory reactions and diseases. These observations suggest
      that agonists and antagonists for lysophospholipid receptors may influence immune
      responses.

PMID- 12069826
TI  - Lysophospholipid regulation of mononuclear phagocytes.
AB  - Blood monocytes and tissue macrophages derived from monocyte differentiation in
      tissues are central elements of innate immunity in host defense against numerous
      pathogens and other challenges. These mononuclear phagocytes also participate in
      wound healing and normal tissue remodeling in development and growth.
      Pathological perversion of their physiological roles leads to participation of
      mononuclear phagocytes in fibrosing diseases including granulomatous disorders,
      chronic inflammation typical of arthritis, and atherosclerosis.
      Lysophospholipids, including lysophosphatidic acid (LPA) and sphingosine 1
      phosphate (S1P), are platelet-derived lipid growth factors considered to
      participate in leukocyte differentiation and activation. This section summarizes
      our recent observations of the effects of lysophospholipids on mononuclear
      phagocytes.

PMID- 12069827
TI  - Sphingosylphosphorylcholine-biological functions and mechanisms of action.
AB  - Compared to the lysophospholipid mediators, sphingosine-1-phosphate (S1P) and
      lysophosphatidic acid (LPA), little information is available regarding the
      molecular mechanisms of action, metabolism and physiological significance of the
      related sphingosylphosphorylcholine (SPC). S1P and LPA have recently been
      established as agonists at several G-protein-coupled receptors of the EDG family,
      S1P additionally serves an intracellular second messenger function. Several
      cellular effects of SPC can be explained by low-affinity binding to and
      activation of S1P-EDG receptors. However, certain cellular and subcellular
      actions of SPC are not shared by S1P, suggesting that SPC, which has been
      identified in normal blood plasma, ascites and various tissues, is a lipid
      mediator in its own right. This concept was corroborated by the recent discovery
      of specific high-affinity G-protein-coupled SPC receptors. In this article, our
      present knowledge on cellular actions and biological functions of SPC will be
      reviewed.

PMID- 12069829
TI  - In vivo roles of lysophospholipid receptors revealed by gene targeting studies in
      mice.
AB  - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are extracellular
      ligands for a family of G protein-coupled receptors (GPCRs), LPA1/2/3 and
      S1P1/2/3/4/5. Through coupling to multiple classes of G proteins and activating
      multiple signaling pathways, LPA/S1P receptors have been shown to be integral
      players for many essential cellular and physiological processes. Generation and
      analysis of mice deficient in each of LPA1, LPA2, S1P1, S1P2, and S1P3 have
      provided valuable information on the in vivo roles of these receptors. This
      review is focussed on expression patterns of each receptor gene in wild-type
      mice, targeted deletion approaches for generating mutant animals, main phenotypes
      of receptor-null mice, and alterations in signaling characteristics in receptor
      deficient primary cells. Altogether, these data give insights to the importance
      of LPA/S1P receptors at the cellular and organismal level.

PMID- 12069828
TI  - Differential effects of sphingosine 1-phosphate and lysophosphatidic acid on
      endothelial cells.
AB  - This review discusses multiple effects of sphingosine 1-phosphate (S1P) and
      lysophosphatidic acid (LPA) on endothelial cells and proposes that S1P and LPA
      are important regulators of the vascular system. Two physiologic sources of S1P
      and LPA are platelets and lipoproteins. S1P is an inducer of angiogenesis in vivo
      whereas LPA is not. S1P and LPA act through endothelial cell surface Edg
      receptors. S1P stimulates endothelial cell migration, but inhibits migration of
      most nonendothelial cells. Edg1 and Edg3 receptors, working through G(i), play an
      important role in regulation of S1P-stimulated endothelial cell migration. LPA
      effects on endothelial cells are more restricted than the effects of S1P on
      endothelial cells. LPA stimulates migration of certain endothelial cells on
      certain extracellular matrix proteins. However, LPA acts like S1P in its effects
      on the endothelial cell cytoskeleton, proliferation, cell-cell adhesion molecule
      expression, and vascular permeability. LPA receptors on endothelial cells are
      likely Edg2 and Edg4. Future studies should better delineate the roles of Edg
      receptors and downstream pathways on effects of extracellular S1P and LPA and the
      contributions of intracellularly generated S1P and nitric oxide (NO).

PMID- 12069830
TI  - Athero- and thrombogenic actions of lysophosphatidic acid and sphingosine-1
      phosphate.
AB  - Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are potent
      bioactive phospholipids with specific and multiple effects on blood cells and
      cells of the vessel wall. Released by activated platelets, LPA and S1P mediate
      physiological wound healing processes such as vascular repair. Evidence is
      accumulating that these lipid mediators can, however, under certain conditions
      become athero- and thrombogenic molecules that might aggravate cardiovascular
      disease. For example, LPA present in minimally modified LDL and within the intima
      of atherosclerotic lesions may play a role in the early phase of atherosclerosis
      by inducing barrier dysfunction and increased monocyte adhesion of the
      endothelium, as well as in the late phase by triggering platelet activation and
      intra-arterial thrombus formation upon rupture of the atherosclerotic plaque.
      Moreover, LPA and S1P, by stimulating the proliferation of fibroblasts and by
      enhancing the survival of inflammatory cells are likely to play a central role in
      the excessive fibroproliferative and inflammatory response to vascular injury
      that characterizes the progression of atherosclerosis. Furthermore, LPA can cause
      the phenotypic dedifferentiation of medial vascular smooth muscle cells, and S1P
      is able to stimulate the migration and proliferation of intimal vascular smooth
      muscle cells; both processes ultimately lead to the formation of the neointima.
      Most importantly, as LPA and S1P bind to and activate multiple G-protein
      receptors, it emerges that the beneficial or harmful action of LPA and S1P are
      critically dependent on the expression profile of their receptor subtypes and
      their coupling to different signal transduction pathways in the target cells. By
      targeting specific subtypes of LPA and S1P receptors in selective cells of the
      vascular wall and blood, new strategies for the prevention and therapy of
      cardiovascular diseases can be envisioned.

PMID- 12069831
TI  - Lysophospholipids and the cardiovascular system.
AB  - The lysophospholipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid
      (LPA) have varied effects on the cardiovascular system. S1P is necessary for
      normal vascular development and may play an important role in angiogenesis. These
      molecules may exert potentially detrimental effects. Both S1P and LPA are
      released from activated platelets and can in turn stimulate platelet aggregation.
      These thrombogenic effects would further enhance ischemia in acute coronary
      syndromes and myocardial infarction. LPA is a major component of the lipid core
      of human atherosclerotic plaques and can stimulate vascular smooth muscle
      proliferation. Both LPA and S1P cause cardiac myocyte hypertrophy in vitro.
      Beneficial effects include cardioprotection both in vitro and during
      ischemia/reperfusion in an ex vivo whole heart mouse model. Understanding both
      the acute and the chronic physiologic and pathophysiologic roles of the
      lysophospholipids and their cognate receptors and signaling pathways in the
      cardiovascular system, which are likely to be species-, tissue-, and cell
      specific, may allow the development of molecules that can be targeted to
      stimulate or inhibit a specific function.

PMID- 12069832
TI  - Sphingosine-1-phosphate receptors and the development of the vascular system.
AB  - Extracellular sphingolipid signaling has been implicated as an essential event in
      vascular development. Sphingosine-1-phosphate (S1P), through interactions with G
      protein-coupled receptors, regulates functions of endothelial and smooth muscle
      cells (SMCs)-the major cell types of the vasculature. The knockout of the gene
      encoding the S1P1 receptor (formally known as Edg-1) in mice blocks vascular
      maturation, the process where SMCs and pericytes envelop nascent endothelial
      tubes. The question that remains is how stimulation of S1P receptors controls
      this critical event in the developmental sequence leading to the formation of
      functional blood vessels.

PMID- 12069834
TI  - Lysophosphatidic acid in airway function and disease.
AB  - Lysophosphatidic acid (LPA) is a bioactive lipid mediator and important component
      of serum. Studies over the past several years which have documented diverse
      effects of LPA on multiple types of airway cells and which suggest possible
      involvement of LPA in lung disease are reviewed here. LPA enhances contractility
      of airway smooth muscle. It also stimulates proliferation of cultured airway
      smooth muscle cells and exhibits a striking synergism with epidermal growth
      factor (EGF) for stimulating mitogenesis. Recent studies of the molecular
      components and signaling pathways mediating synergism are described, including
      LPA-induced upregulation of EGF receptors and activation of multiple
      transcription factors by both LPA and EGF. A model for the effects of LPA and EGF
      on mitogenesis that includes EGF receptor upregulation and synergism between Ras
      and Rho for activation of the transcription factor AP-1 is presented. LPA
      stimulates fibronectin secretion and filopodia extension in airway epithelial
      cells as well as proliferation and collagen gel contraction by lung fibroblasts.
      A hypothesis for LPA involvement in the airway repair and remodeling, which
      contribute to the pathology of asthma and other airway diseases, is presented,
      and future directions for research into the roles of LPA in airway function and
      disease are suggested.

PMID- 12069833
TI  - Lipid mediators of angiogenesis and the signalling pathways they initiate.
AB  - Investigations carried out over the past 3 years have implicated a key role for
      sphingosine 1-phosphate (SPP) in angiogenesis and blood vessel maturation. SPP is
      capable of inducing almost every aspect of angiogenesis and vessel maturation in
      vitro, including endothelial cell chemotaxis, survival, proliferation, capillary
      morphogenesis and adherence antigen deployment, as well as stabilizing developing
      endothelial cell monolayers and recruitment of smooth muscle cells to maturing
      vessels. Acting in conjunction with protein angiogenic factors, SPP induces
      prolific vascular development in many established models of angiogenesis in vivo.
      Thus, SPP is a unique, potent and multifaceted angiogenic agent. While SPP
      induces angiogenic effects by ligating members of the endothelial differentiation
      gene (EDG) G-protein-coupled family of receptors, recent studies suggest that
      endogenously produced SPP may also account for the ability of tyrosine kinase
      receptors to induce cell migration. Thus, SPP provides a clear link between
      tyrosine kinase and G-protein-coupled receptor agonists involved in the
      angiogenic response. However, the mechanisms by which SPP exerts its effects on
      vascular cells remain unclear, conflicting and controversial. Precise definition
      of the signalling pathways by which SPP induces specific aspects of the
      angiogenic response promises to lead to new and effective therapeutic approaches
      to regulate angiogenesis at sites of tissue damage, neoplastic transformation and
      inflammation. This review will trace the discovery of SPP as a novel angiogenic
      factor as it outlines present information on the signalling pathways by which SPP
      induces its effects on cells of the developing vascular bed.

PMID- 12069835
TI  - EDG receptors and hepatic pathophysiology of LPA and S1P: EDG-ology of liver
      injury.
AB  - The biological roles of phospholipid growth factors lysophosphatidic acid (LPA)
      and sphingosine-1-phosphate (S1P) have been broadly investigated. The cellular
      effects of LPA and S1P are mediated predominantly via endothelial differentiation
      gene (EDG) receptors. Yet, the biological significance of LPA, S1P and their EDG
      receptors in cells of the liver remains unclear. Recent data demonstrate the
      presence of EDG2 and EDG4 mRNA for LPA receptor in a murine hepatocyte cell line
      transformed with human TGF-alpha, and in primary mouse hepatocytes. EDG2 receptor
      protein is expressed in mouse liver, where it appears to be located in
      nonparenchymal cells. Moreover, we have obtained data suggesting that
      proliferation of small hepatocyte-progenitors and stem (oval) cells during liver
      injury is associated with the expression of EDG2 and EDG4 receptors. LPA, and
      possibly S1P, appear to be essential factors that control proliferation and
      motility of hepatic stellate cells (HSC) and hepatoma cells. It is proposed that
      LPA, S1P and their respective EDG receptors play important roles in
      pathophysiology of chronic liver injury and fibrogenesis. The underlying
      mechanisms recruited by LPA and S1P in pathogenesis of liver injury remain to be
      investigated.

PMID- 12069836
TI  - Lysophosphatidic acid is a bioactive mediator in ovarian cancer.
AB  - Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that exhibits
      pleiotrophic biological activities, ranging from rapid morphological changes to
      long-term cellular effects such as induction of gene expression and stimulation
      of cell proliferation and survival on a wide spectrum of cell types. LPA binds
      and activates distinct members of the Edg/LP subfamily of G protein-coupled
      receptors that link to multiple G proteins including Gi, Gq and G12/13 to elicit
      cellular responses. LPA plays a critical role as a general growth, survival and
      pro-angiogenic factor, in the regulation of physiological and pathophysiological
      processes in vivo and in vitro. Our previous work indicates that abnormalities in
      LPA metabolism and function in ovarian cancer patients may contribute to the
      initiation and progression of the disease. Thus, LPA could be a potential target
      for cancer therapy. This review summarizes evidence that implicates LPA in the
      pathophysiology of human ovarian cancer and likely other types of human
      malignancies.

PMID- 12069837
TI  - Mitogenic action of LPA in prostate.
AB  - The lipid growth factor lysophosphatidic acid (LPA) elicits multiple cellular
      responses, including cell growth and survival. LPA acts upon target cells by
      activating its cognate receptors, which belong to the G protein-coupled
      endothelial differentiation gene (EDG) family. To date, three known LPA
      receptors, termed LPA1, LPA2 and LPA3, have been molecularly characterized and
      cloned. Here, we review recent data describing the molecular steps involved in
      the LPA receptor-mediated activation of mitogenic extracellular signal-regulated
      kinase (ERK) pathway in prostate cancer. Induction of ERK by LPA proceeds via
      Gbetagamma-dependent activation of tyrosine kinases, including the epidermal
      growth factor (EGF) receptor and c-Src. Further, LPA-induced ERK activation
      involves matrix metalloproteinases (MMPs), which cause the release of active EGFR
      ligands. Finally, we present data demonstrating a correlation between the
      mitogenic effects of LPA and expression of the lp(A1) gene in the prostate cancer
      cells.

PMID- 12069838
TI  - Lysophosphatidic acid as an autocrine and paracrine mediator.
AB  - Recent studies have established that lysophosphatidic acid (LPA) is produced by a
      wide variety of cell types, and that most mammalian cells express receptors for
      LPA. These findings raise the hypothesis that LPA acts as an autocrine mediator
      to initiate signaling in the cells where it is produced, as well as a paracrine
      mediator to affect neighboring cells. The extent to which these scenarios occur
      will depend on the species of LPA generated, the LPA receptors expressed, and the
      ability of these receptors to bind to the LPA produced. The enzymes involved in
      LPA synthesis and their cellular localization in relationship to LPA receptors
      are also likely to be important. Studies addressing these issues with respect to
      the potential roles of LPA as an autocrine and paracrine mediator are reviewed,
      with examples.

PMID- 12069839
TI  - Modulation of gastrointestinal wound repair and inflammation by phospholipids.
AB  - The mucosal surface of the digestive tract is a critical barrier between a broad
      spectrum of noxious and immunogenic substances present in the gastrointestinal
      lumen and the underlying mucosal immune system. Its preservation following
      various forms of injury or physiological damage is essential to prevent the
      invasion of harmful luminal factors into the host, which subsequently may lead to
      inflammation, uncontrolled immune response, and a disequilibrium of the
      homeostasis of the host. The preservation of this barrier following injuries is
      regulated by a broad spectrum of structurally distinct regulatory molecules,
      including phospholipids. Phospholipids play a pivotal role in the modulation of
      intestinal inflammation. They have been demonstrated to both promote and inhibit
      inflammation, and their overall impact in an individual setting seems to be
      dependent on several factors, including the level of immune cell activation and
      the presence of other mediators. Modulation of lipid mediators through
      administration of lysophosphatidic acid (LPA) or lisofylline (LSF), inhibitors of
      phospholipase A2 (PLA2) biosynthesis or monoclonal antibodies against thromboxane
      (TBX) or platelet-activating factor (PAF) as a therapeutic approach have been
      used in several models of inflammation; however, beneficial effects were not
      always convincing and further studies are warranted.

PMID- 12069840
TI  - Structure-activity relationships of lysophosphatidic acid analogs.
AB  - The physiologic effects of lysophosphatidic acid (LPA) remain poorly understood.
      Our ignorance is due in part to lack of medicinal chemistry focussed on this
      pleiotropic lipid mediator. Beginning with commercially available phospholipids
      tested on whole cells or tissues and continuing with synthetic analogs tested at
      recombinant LPA receptors, the features of the LPA pharmacophore have become
      visible. An active LPA mimetic has a long aliphatic chain terminating in a
      phosphate monoester; bulky substitutions at the second carbon (relative to the
      phosphate) are tolerated poorly and a dissociable proton near the phosphate group
      seems required for optimal activity. These requirements are met by substituting
      ethanolamine for the glyceryl group in LPA. Substitutions at the second carbon of
      the N-acyl ethanolamide phosphoric acid (NAEPA) result in highly active agonists,
      including some receptor type selective compounds, if the substituent is small
      (e.g. methyl, methylene amino, methylene hydroxy). However, bulky hydrophobic
      substituents lead to compounds with decreased agonist, or even antagonist,
      activities. Examination of naturally occurring plant lipids led to the discovery
      of another LPA receptor antagonist, di-octyl glyceryl pyrophosphate. An
      unexplained result obtained in testing the LPA mimetics is the strong
      stereoselectivity exhibited by some responses (e.g. calcium mobilization) and the
      lack of stereoselectivity of other responses (e.g. platelet aggregation).

PMID- 12069841
TI  - Stereochemical properties of lysophosphatidic acid receptor activation and
      metabolism.
AB  - Ligand recognition by G protein-coupled receptors (GPCR), as well as substrate
      recognition by enzymes, almost always shows a preference for a naturally
      occurring enantiomer over the unnatural one. Recognition of lysophosphatidic acid
      (LPA) by its receptors is an exception, as both the natural L (R) and unnatural D
      (S) stereoisomers of LPA are equally active in bioassays. In contrast to the
      enantiomers of LPA, analogs of N-acyl-serine phosphoric acid (NASPA) and N-acyl
      ethanolamine phosphoric acid (NAEPA), which contain a serine and an ethanolamine
      backbone, respectively, in place of glycerol, are recognized in a stereoselective
      manner. This stereoselective interaction may lead to the development of receptor
      subtype-selective antagonists. In the present study, we review the stereochemical
      aspects of LPA pharmacology and describe the chemical synthesis of pure LPA
      enantiomers together with their ligand-binding properties toward the LPA1, LPA2,
      and LPA3 receptors and their metabolism by lipid phosphate phosphatase 1 (LPP1).
      Finally, we evaluate the concept of stereopharmacology in developing novel
      ligands for LPA receptors.

PMID- 12069844
TI  - Shedding light on the metabolism of phospholipids in the retina.

PMID- 12069842
TI  - Molecular basis for lysophosphatidic acid receptor antagonist selectivity.
AB  - Recent characterization of lysophosphatidic acid (LPA) receptors has made
      possible studies elucidating the structure-activity relationships (SAR) for
      agonist activity at individual receptors. Additionally, the availability of these
      receptors has allowed the identification of antagonists of LPA-induced effects.
      Two receptor-subtype selective LPA receptor antagonists, one selective for the
      LPA1/EDG2 receptor (a benzyl-4-oxybenzyl N-acyl ethanolamide phosphate, NAEPA,
      derivative) and the other selective for the LPA3/EDG7 receptor (diacylglycerol
      pyrophosphate, DGPP, 8:0), have recently been reported. The receptor SAR for both
      agonists and antagonists are reviewed, and the molecular basis for the difference
      between agonism and antagonism as well as for receptor-subtype antagonist
      selectivity identified by molecular modeling is described. The implications of
      the newly available receptor-subtype selective antagonists are also discussed.

PMID- 12069845
TI  - Sphingolipid functions in Saccharomyces cerevisiae.
AB  - Recent advances in understanding sphingolipid metabolism and function in
      Saccharomyces cerevisiae have moved the field from an embryonic, descriptive
      phase to one more focused on molecular mechanisms. One advance that has aided
      many experiments has been the uncovering of genes for the biosynthesis and
      breakdown of sphingolipids. S. cerevisiae seems on the verge of becoming the
      first organism in which all sphingolipid metabolic genes are identified. Other
      advances include the demonstration that S. cerevisiae cells have lipid rafts
      composed of sphingolipids and ergosterol and that specific proteins associate
      with rafts. Roles for phytosphingosine (PHS) and dihydrosphingosine (DHS) in heat
      stress continue to be uncovered including regulation of the transient cell cycle
      arrest, control of putative signaling pathways that govern cell integrity,
      endocytosis, movement of the cortical actin cytoskeleton and regulation of
      protein breakdown in the plasma membrane. Other studies suggest roles for
      sphingolipids in exocytosis, growth regulation and longevity. Finally, some
      progress has been made in understanding how sphingolipid synthesis is regulated
      and how sphingolipid levels are maintained.

PMID- 12069846
TI  - Possible participation of intracellular platelet-activating factor in NF-kappaB
      activation in rat peritoneal macrophages.
AB  - As we had found previously that thapsigargin, an endomembrane Ca2+-ATPase
      inhibitor, induces production of intracellular platelet-activating factor (PAF)
      [Br. J. Pharmacol. 116 (1995) 2141], we decided to investigate the possible roles
      of intracellular PAF in nuclear factor (NF)-kappaB activation of thapsigargin
      stimulated rat peritoneal macrophages. When rat peritoneal macrophages were
      stimulated with thapsigargin, the level of inhibitory protein of NF-kappaB-alpha
      (IkappaB-alpha) was decreased and the nuclear translocation of NF-kappaB was
      increased. The thapsigargin-induced activation of NF-kappaB was inhibited by the
      PAF synthesis inhibitor SK&F 98625 and the PAF antagonist E6123. Structurally
      unrelated PAF antagonists such as E5880 and L-652,731 also inhibited the
      thapsigargin-induced activation of NF-kappaB. Lipopolysaccharide (LPS)-induced
      activation of NF-kappaB was also suppressed by these drugs. In a culture of rat
      peritoneal macrophages, exogenously added PAF did not induce degradation of
      IkappaB-alpha. These findings suggest that the intracellular PAF produced by the
      stimulation with thapsigargin or LPS is involved in activation of the NF-kappaB
      pathway.

PMID- 12069847
TI  - The effects of lysosomotropic agents on normal and INCL cells provide further
      evidence for the lysosomal nature of palmitoyl-protein thioesterase function.
AB  - Fatty acylation of proteins on cysteine residues is a common post-translational
      modification that plays roles in protein-membrane and protein-protein
      interactions. Recently, we described a lysosomal palmitoyl-protein thioesterase
      that removes long-chain fatty acids from lipid-modified cysteine residues in
      proteins. Deficiency in palmitoyl-protein thioesterase results in a human
      lysosomal storage disorder, infantile neuronal ceroid lipofuscinosis (INCL),
      which primarily affects the central nervous system. The pathological hallmark of
      the disorder is the accumulation of granular osmiophilic deposits (GROD) that
      resemble lipofuscin, or aging pigment. In previous work, we have shown that
      [35S]cysteine-labeled lipid thioesters derived from fatty acylated proteins
      accumulate in cultured cells derived from palmitoyl-protein thioesterase
      deficient patients. In the present work, we show that the lipid cysteine
      thioesters accumulate in the lysosomal fraction, and we further show that the
      appearance of these compounds in the organic phase is blocked by inhibitors of
      lysosomal proteolysis, demonstrating through biochemical means the lysosomal
      nature of the site of palmitoyl-protein thioesterase action. Furthermore,
      substrates for palmitoyl-protein thioesterase accumulate even in normal cells
      after leupeptin or chloroquine treatment. This was demonstrated by subjecting
      extracts of treated cells to exhaustive proteolysis to release protein-bound
      cysteine lipid for analysis. Cysteamine, a lysosomotropic drug recently proposed
      for the treatment of INCL, was found to have effects similar to leupeptin and
      chloroquine, suggesting that its mechanism of action may be more complex than
      previously understood.

PMID- 12069848
TI  - Selective mutagenesis of lysyl residues leads to a stable and active form of
      delta 9 stearoyl-CoA desaturase.
AB  - Stearoyl-CoA desaturase (SCD) is a short-lived integral membrane protein of the
      endoplasmic reticulum (ER) that catalyzes the insertion of a double bond in the
      delta 9 position of saturated fatty acids. Its expression has been difficult in
      heterologous systems. In this study, recombinant adenovirus vector was used to
      express both wild-type (wt) and engineered forms of rat SCD in human transformed
      kidney cells. In the engineered form of SCD, lysyl residues at positions 33, 35,
      and 36 were mutated to alanine (SCD K/A). The recombinant adenovirus also
      contains a cDNA encoding the green fluorescent protein (GFP). The stable reporter
      GFP was used to analyze the efficiency of transfection and the stability of
      expressed SCDs. The wt SCD was unstable upon expression, whereas expression of
      SCD K/A resulted in the stabilization of the protein. The proteasome inhibitor
      MG132 did not affect the rapid degradation of expressed wt SCD, implying that
      proteasome is not involved in this degradation. Functional analysis of microsomes
      from infected cells expressing SCD K/A resulted in the formation of holoenzyme
      with desaturase activity. Here we report engineering a stabilized form of a
      rapidly degraded membrane protein for production of an active mutant form of SCD.
      The adenovirus transformed cells may provide a model for the study of the effects
      of positive SCD expression.

PMID- 12069849
TI  - Human mast cells express two leukotriene C(4) synthase isoenzymes and the
      CysLT(1) receptor.
AB  - Cysteinyl-leukotrienes (cys-LTs) are potent smooth muscle contracting agents,
      especially in the respiratory tract and microcirculation, and play a key role in
      inflammatory and allergic diseases. The final step in the biosynthesis of LTC(4),
      the parent compound of cys-LTs, is catalyzed by a specific GSH transferase termed
      LTC(4) synthase, which is typically expressed in certain bone marrow-derived
      cells such as eosinophils and mast cells. Here we report that the human mast cell
      line HMC-1 as well as human mast cells derived from cord blood (CBMC) express a
      second enzyme capable of synthesizing leukotriene C(4), i.e., microsomal GSH
      transferase type 2. Furthermore, these cells abundantly express CysLT(1)
      receptors that are mostly located at the surface of both types of mast cells, as
      judged by immunohistochemistry. In addition, stimulation of CBMC with LTC(4) and
      LTD(4) elicits an immediate and dose-dependent (10(-7)-10(-11) M) mobilization of
      intracellular Ca(2+), which can be blocked with specific CysLT(1) receptor
      antagonists. Taken together, our data suggest that human mast cells are equipped
      with two enzymes that can catalyze the committed step in the biosynthesis of cys
      LTs. Moreover, the expression of the cognate receptor CysLT(1) suggests that
      these lipid mediators may be involved in autocrine signaling pathways regulating
      mast cell functions.

PMID- 12069850
TI  - On the mechanism of bile acid inhibition of rat sterol 12alpha-hydroxylase gene
      (CYP8B1) transcription: roles of alpha-fetoprotein transcription factor and
      hepatocyte nuclear factor 4alpha.
AB  - The sterol 12alpha-hydroxylase (CYP8B1) is a key enzyme of the bile acid
      biosynthetic pathway. It regulates the composition of bile acids in bile, i.e.
      ratio between cholic acid (CA) and chenodeoxycholic acid (CDCA). In similarity
      with cholesterol 7alpha-hydroxylase (CYP7A1), this enzyme is subjected to a
      negative feedback regulation by bile acids. It has been recently reported that
      bile acid-activated farnesoid X receptor (FXR) induces the small heterodimer
      partner (SHP) that interacts with alpha-fetoprotein transcription factor (FTF)
      and down-regulates CYP7A1 transcription. We studied whether the same mechanism
      also regulated rat CYP8B1 gene transcription. Feeding rats with CDCA caused a 40
      50% decrease of CYP8B1 and hepatocyte nuclear factor 4alpha (HNF4alpha) mRNA
      expression levels. This was associated with an increase in FTF mRNA expression,
      but SHP mRNA expression was not altered. Electrophoretic mobility shift assay
      (EMSA) and transient transfection assay of promoter/reporter genes coupled to
      mutagenesis analysis identified a putative bile acid response element (BARE) that
      has an HNF4alpha binding site embedded in two overlapping FTF binding sites.
      Mutation of the HNF4alpha binding site markedly reduced basal promoter activity
      and its repression by bile acids. Cotransfection with FTF strongly repressed
      CYP8B1 transcription. Interestingly, HNF4alpha could overcome the inhibitory
      effects of FTF and bile acids. We conclude that FTF and HNF4alpha not only play
      critical roles on CYP8B1 gene transcription, but also mediate bile acid feedback
      inhibition. This study reveals a novel mechanism by which bile acids inhibit rat
      CYP8B1 gene transcription by inducing FTF and inhibiting HNF4alpha expression.

PMID- 12069851
TI  - Gamma-linolenic acid alters the composition of mitochondrial membrane
      subfractions, decreases outer mitochondrial membrane binding of hexokinase and
      alters carnitine palmitoyltransferase I properties in the Walker 256 rat tumour.
AB  - Gamma-linolenic acid (GLA) is known to be an inhibitor of Walker 256 tumour
      growth in vivo and causes changes in both mitochondrial structure and cellular
      metabolism. The aim of the present study was to investigate in greater detail the
      changes in energy metabolism and ultrastructure induced by GLA in this tumour
      model. A diet containing 5.5% GLA, which is sufficient to cause a 45% decrease in
      tumour growth, was found to almost double the triacylglycerol (TAG) content of
      the tumour and to increase the quantity of 20:3 n-6, 20:4 n-6, 22:4 n-6 and 22:5
      n-6 in the TAG fraction as determined by gas chromatography-mass spectrometry
      (GCMS) analysis. Morphometric analysis of the tumour by electron microscopy
      confirmed this increase in TAG content, identifying a doubling of lipid droplet
      content in the GLA dietary group. The surface density of mitochondrial cristae
      was reduced, along with a reduction in the number of contact sites (CS) and
      matrix granules. These three parameters are likely indicators of a reduction in
      mitochondrial metabolic activity. Measurement of hexokinase activity identified
      that much of the total hexokinase activity was in the mitochondrially bound form
      (66.5%) in the control tumour and that GLA caused a decrease in the amount of
      enzyme in the bound form (39.3%). The fatty acyl chain composition of the tumour
      mitochondrial subfractions, outer membranes (OM), CSs and inner membranes (IM)
      was determined by GCMS. All subfractions showed considerable increases in 20:3 n
      6 and decreases in 18:1 n-9, 18:2 n-6 and 22:6 n-3, when exposed to GLA diet.
      These changes were reflected in a large increase in the n-6/n-3 ratio in the GLA
      OM vs. the control OM, 21.299 vs. 6.747, respectively. The maximal activity of OM
      carnitine palmitoyltransferase I (CPT I) was found to be decreased by 61.6% in
      the GLA diet group. This was accompanied by a decrease in malonyl CoA sensitivity
      and a decrease in affinity for 16:0 CoA substrate. Such changes in CPT I may be
      the cause of cytoplasmic acyl CoA accumulation seen in this tumour model. These
      effects, together with previously reported increases in lipid peroxidation, lead
      to the conclusion that GLA may cause inhibition of tumour cell growth through
      separate but interlinked pathways, all of which eventually lead to apoptosis and
      a decrease in tumour development. The influence of mitochondrial OM fatty acyl
      chain composition upon two important enzymes of energy metabolism, hexokinase and
      CPT I, both of which have been linked to apoptosis, is of considerable importance
      for future studies on fatty acid-induced cell death.

PMID- 12069852
TI  - Immunolocalization of long-chain acyl-CoAs in plant cells.
AB  - Long chain acyl-Coenzyme A esters (acyl-CoAs) are key substrates in many enzymic
      reactions of lipid metabolism. Due to their amphiphilic nature, the membrane
      localization of these molecules cannot be established by subcellular membrane
      fractionation and usual biochemical studies. We have developed another approach
      based on ultrastructural immunogold cytochemistry. To preserve the acyl-CoA
      membrane content, the plant material was freeze substituted and cryoembedded
      after short aldehyde fixation followed by quick freezing. Using Arabidopsis
      thaliana root cells and specific antibodies raised against acyl-CoAs, we show
      that acyl-CoAs are mainly localized in endoplasmic reticulum membranes. Our
      results demonstrate the value of cryo-methods for the accurate localization of
      labile metabolites in plant cells.

PMID- 12069853
TI  - Vitamin E deficiency sensitizes alveolar type II cells for apoptosis.
AB  - Pre-term neonates and neonates in general exhibit physiological vitamin E
      deficiency and are at increased risk for the development of acute lung diseases.
      Apoptosis is a major cause of acute lung damage in alveolar type II cells. In
      this paper, we evaluated the hypothesis that vitamin E deficiency predisposes
      alveolar type II cells to apoptosis. Therefore, we measured markers of apoptosis
      in alveolar type II cells isolated from control rats, vitamin E deficient rats
      and deficient rats that were re-fed a vitamin E-enriched diet. Bax and cytosolic
      cytochrome c increased, and the mitochondrial transmembrane potential and Hsp25
      expression was reduced in vitamin E deficiency. Furthermore, increased DNA
      fragmentation and numbers of early and late apoptotic cells were seen, but
      caspases 3 and 8 activities and expression of Fas, Bcl-2, Bcl-x and p53 remained
      unchanged. Vitamin E depletion did not change the GSH/GSSG ratio and the
      activities of antioxidant enzymes. Thus, vitamin E deficiency may induce a
      reversible pro-apoptotic response in lung cells and sensitise them for additional
      insult. In agreement with this hypothesis, we demonstrate that in vivo hyperoxia
      alone does not induce apoptosis in type II cells of control rats but reversibly
      increases DNA-fragmentation and numbers of early apoptotic type II cells in
      vitamin E-depleted cells.

PMID- 12069854
TI  - Early-glycation of apolipoprotein E: effect on its binding to LDL receptor,
      scavenger receptor A and heparan sulfates.
AB  - Glycation is responsible for disruption of lipoprotein functions leading to the
      development of atherosclerosis in diabetes. The effects of apolipoprotein E
      (apoE) glycation were investigated with respect to its interaction with
      receptors. The interaction of apoE with the low density lipoprotein receptor (LDL
      R) and scavenger receptor A (SR-A) was measured by competition experiments
      performed using, respectively, on a human fibroblast cell line 125I-LDL, and on a
      murine macrophage cell line (J774) 125I-acetylated LDL, and unlabeled
      apoE/phospholipid complexes. Glycated apoE binding to heparin and heparan
      sulfates (HS) was assessed by surface plasmon resonance (SPR) technology. Site
      directed mutagenesis was then performed on Lys-75, the major glycation site of
      the protein. The prepared mutant protein proved to be useful as a tool to study
      the role of Lys-75 in apoE glycation. The findings showed that, although
      glycation has no effect on apoE binding either to the LDL-R or to SR-A, it
      impairs its binding to immobilized heparin and HS. The glycation of Lys-75 was
      found to be proceed rapidly and contributed significantly to total protein
      glycation. We propose that, in the case of diabetes, glycation may lead to the
      atherogenicity of apoE-containing lipoproteins disturbing their uptake via the HS
      proteoglycan pathway.

PMID- 12069855
TI  - Activator protein-1 and CCAAT/enhancer-binding protein mediated GADD153
      expression is involved in deoxycholic acid-induced apoptosis.
AB  - Studies have demonstrated bile acids, principally deoxycholic acid (DCA), to be
      colon tumor promoters. DCA is cytotoxic and increasing evidence suggests a role
      for DCA-induced apoptosis in colon tumorigenesis. Although the precise mechanism
      by which DCA induces apoptosis remains unclear, DCA may affect cell growth and
      cell death via altering intracellular signaling and gene expression. In this
      study, we examined the effect of DCA on the GADD153 (growth arrest- and DNA
      damage-inducible gene 153) proapoptotic gene and its role in DCA-induced
      apoptosis in a human colon cancer cell line, HCT116. Our results showed that
      GADD153 expression was strongly stimulated by DCA and disruption of this with an
      antisense GADD153 transcript could significantly suppress DCA-induced apoptosis,
      suggesting GADD153 is essential for DCA induction of apoptosis. Further studies
      were conducted to investigate the upstream regulatory factors that participated
      in DCA mediated GADD153 expression. Activator protein-1 (AP-1) was activated by
      DCA and an AP-1 regulatory element was identified in the human GADD153 promoter
      in our previous studies. However, inhibition of the AP-1 activation by the
      dominant negative mutant c-Jun, Tam67, caused only a partial suppression of both
      DCA-induced GADD153 expression and apoptosis, indicating AP-1 plays an important
      but not exclusive role in DCA mediated GADD153 pathway. By further promoter
      analyses, a novel DCA response element, which is located downstream of the AP-1
      binding site in the human GADD153 promoter, was determined and identified as
      C/EBP regulatory element. These results suggest that GADD153 expression is
      critical for DCA-induced apoptosis and that multiple signaling pathways that
      include AP-1 and C/EBP transcription factors are involved in DCA-induced GADD153
      expression.

PMID- 12069856
TI  - A case of hyperlipidemia with homozygous apolipoprotein E5 (Glu3-->Lys).
AB  - In this study, we present clinical feature of a novel case with homozygous
      apolipoprotein (apo) E5. The patient was a 53-year-old Japanese woman. She was
      from a small island off the coast of Kagoshima Prefecture, Japan. Her parents
      were first degree cousins. No corneal opacification, xanthomatosis,
      lymphadenopathy, or hepatosplenomegaly was observed. There have been no signs of
      clinically overt atherosclerosis to date. Her serum total cholesterol,
      triglycerides (TG) and high-density lipoprotein (HDL)-cholesterol levels were
      11.6, 6.1 and 1.2 mmol/l, respectively, and apo A-I, A-II, B, C-II, C-III and E
      levels were 121, 34.8, 269, 10.4, 25.7 and 10.3 mg/dl, respectively. Serum
      lipoprotein profile analyzed by agarose gel electrophoresis and differential
      staining revealed markedly increased cholesterol and TG in both beta and prebeta
      migrated lipoproteins, whereas alpha-migrated lipoprotein showed decreased
      cholesterol. Her apo E isoform analyzed by isoelectric focusing (IEF) was found
      to be homozygous apo E5. Polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP) analysis of her apo E and lipoprotein lipase (LPL) genes
      revealed that she had a homozygous apo E (Glu3-->Lys) and heterozygous LPL
      variant Ser447 to Ter. Her son and daughter, both of whom had hyperlipidemia,
      were found to have apo E3/5 phenotype. Direct sequencing analysis of her apo E
      gene confirmed a homozygous one nucleotide change: G to A at nucleotide position
      of 2836 in the exon 3, resulting in Glu3-->Lys mutation. This is the first report
      of lipids and lipoprotein profiles in patients with homozygous apo E5 (Glu3-
      >Lys).

PMID- 12069857
TI  - Processive interfacial catalytic turnover by Bacillus cereus sphingomyelinase on
      sphingomyelin vesicles.
AB  - Sphingomyelinase (SMase), a water-soluble enzyme from Bacillus cereus, is shown
      to bind with high affinity to vesicles of sphingomyelin (SM) but not to vesicles
      of phosphatidylcholine (PC). The reaction progress by SMase bound to SM vesicles
      occurs in the scooting mode with virtually infinite processivity of the
      successive interfacial turnover cycles. Three conditions for the microscopic
      steady state during the reaction progress at the interface are satisfied: the
      bound SMase does not leave the interface even after all the SM in the outer layer
      is converted to ceramide; the SMase-treated vesicles remain intact; and the
      ceramide product does not exchange with SM present in excess vesicles or in the
      inner layer of the hydrolyzed vesicle. Within these constraints, on accessibility
      and replenishment of the substrate, the extent of hydrolysis in the scooting mode
      reaction progress is a measure of the number of vesicles containing enzyme. The
      slope of the Poisson distribution plot, for the enzyme per vesicle versus the
      logarithm of the fraction of the total accessible substrate remaining
      unhydrolyzed in excess vesicles, shows that a single 32 kDa subunit of SMase is
      fully catalytically active. The maximum initial rate of hydrolysis, at the limit
      of the maximum possible substrate mol fraction, X(S)*=1, is 400 s(-1) in H(2)O
      and 220 s(-1) in D(2)O, which is consistent with the rate-limiting chemical step.
      The integrated reaction progress suggests that the ceramide product does not
      codisperse ideally on the hydrolyzed vesicles. Furthermore, complex reaction
      progress seen with covesicles of SM+PC are attributed to slow secondary changes
      in the partially hydrolyzed SM vesicles.

PMID- 12069859
TI  - Guidelines for sperm donation.

PMID- 12069860
TI  - Guidelines for oocyte donation.

PMID- 12069861
TI  - Guidelines for cryopreserved embryo donation.

PMID- 12069862
TI  - Psychological assessment of gamete donors and recipients.

PMID- 12069863
TI  - Psychological guidelines for embryo donation.

PMID- 12069864
TI  - Minimal genetic screening for gamete donors.

PMID- 12069865
TI  - Chronic fatigue: listen and measure.

PMID- 12069866
TI  - The English Chief Medical Officer's Working Parties' report on the management of
      CFS/ME: significant breakthrough or unsatisfactory compromise?

PMID- 12069868
TI  - Fatigue and psychological distress in the working population: psychometrics,
      prevalence, and correlates.
AB  - OBJECTIVE: The purposes of this study were: (1) to explore the relationship
      between fatigue and psychological distress in the working population; (2) to
      examine associations with demographic and health factors; and (3) to determine
      the prevalence of fatigue and psychological distress. METHODS: Data were taken
      from 12,095 employees. Fatigue was measured with the Checklist Individual
      Strength, and the General Health Questionnaire (GHQ) was used to measure
      psychological distress. RESULTS: Fatigue was fairly well associated with
      psychological distress. A separation between fatigue items and GHQ items was
      shown. No clear, distinct pattern of associations was found for fatigue vs.
      psychological distress with respect to demographic factors. The prevalence was
      22% for fatigue and 23% for psychological distress. Of the employees reporting
      fatigue, 43% had fatigue only, whereas 57% had fatigue and psychological
      distress. CONCLUSIONS: The results indicate that fatigue and psychological
      distress are common in the working population. Although closely associated, there
      is some evidence suggesting that fatigue and psychological distress are different
      conditions, which can be measured independently.

PMID- 12069867
TI  - Use of actigraphy for monitoring sleep and activity levels in patients with
      fibromyalgia and depression.
AB  - OBJECTIVE: The hallmark symptom of fibromyalgia (FM) is widespread chronic pain,
      but most patients are also impaired due to fatigue and sleep disturbance, and
      there is a strong association with depression. We compared levels of activity and
      sleep patterns in FM patients, with and without comorbid depression, to those of
      normal healthy controls and depressed patients. METHODS: Actigraphy was carried
      out on 16 patients with uncomplicated FM, 6 FM patients with comorbid depression,
      9 patients with recurrent major depression, and 28 healthy controls over a period
      of 5-7 days. The means of daytime activity levels, nighttime activity levels, and
      percentage time spent asleep during the daytime and nighttime were calculated and
      compared. RESULTS: Controls showed high levels of activity during the day and
      uninterrupted periods of sleep at night. Patients with FM alone showed similar
      levels of daytime activity, but disturbed sleep with significantly increased
      levels of activity at night compared to normal controls. Patients with depression
      alone also showed disturbed sleep compared to normal controls. However, patients
      with FM and comorbid depression showed the most impairment, with significantly
      reduced daytime activity and significantly increased daytime sleeping compared to
      controls, as well as more sleep interruption and movement during the night.
      CONCLUSION: Actigraphy is a useful means of studying activity levels and sleep
      patterns and demonstrated significant differences between FM patients with and
      without comorbid depression.

PMID- 12069869
TI  - Fatigue after breast cancer and in chronic fatigue syndrome: similarities and
      differences.
AB  - OBJECTIVE: Fatigue is investigated in 57 severely fatigued disease-free breast
      cancer patients and in 57 gender- and age-matched patients with chronic fatigue
      syndrome (CFS) using multidimensional and multimethod assessment. A comparison
      between these groups of patients is important to determine whether a cognitive
      behavioural intervention to reduce fatigue in CFS patients would be appropriate
      as well for severely fatigued disease-free breast cancer patients. METHODS:
      Measurement included computerised questionnaires and a standardised
      neuropsychological test. Furthermore, patients filled out a daily Self
      Observation List (SOL) and wore an actometer during a period of 12 days. RESULTS:
      In comparison to severely fatigued disease-free breast cancer patients, CFS
      patients score more problematic with regard to the level of fatigue, functional
      impairment, physical activity, pain and self-efficacy. However, a subgroup of
      severely fatigued disease-free breast cancer patients reports the same amount of
      problems as CFS patients with regard to psychological well-being, sleep and
      concentration. Finally, CFS patients and severely fatigued breast cancer patients
      score equal on measures of social support. CONCLUSION: There seem to be some
      similarities but also many differences between severely fatigued breast cancer
      survivors and females with CFS. Therefore, cognitive behaviour therapy (CBT) to
      reduce fatigue after treatment for cancer should also differ in certain aspects
      from cognitive behaviour therapy as it has been developed for patients with CFS.

PMID- 12069870
TI  - Illness experience, depression, and anxiety in chronic fatigue syndrome.
AB  - OBJECTIVE: Given the high rate of psychiatric comorbidity with chronic fatigue
      syndrome (CFS), we considered two possible correlates of anxiety and depression:
      lack of illness legitimization and beliefs about limiting physical activity.
      METHOD: A total of 105 people diagnosed with CFS reported on their experiences
      with medical professionals and their beliefs about recovery and completed the
      depression and anxiety subscales of the Brief Symptom Inventory. RESULTS: Those
      who said that their physician did not legitimize their illness (36%) had higher
      depression and anxiety scores (P's<.05) than their counterparts. Those who
      believed that limiting their physical exertion was the path to recovery (55%) had
      lower depression and anxiety scores (P's<.01) than their counterparts.
      CONCLUSION: Lack of illness legitimization ranked high as a source of
      dissatisfaction for CFS patients, and it may aggravate psychiatric morbidity.
      Many CFS patients believed that staying within what they felt to be their
      physical limits would improve their condition. This belief, and possibly an
      accompanying sense of control over their symptoms, may alleviate psychiatric
      morbidity.

PMID- 12069871
TI  - Development of an adjective checklist to measure five FACES of fatigue and
      sleepiness. Data from a national survey of insomniacs.
AB  - Development and initial validation of the FACES of fatigue and sleepiness
      adjective checklist. An initial item pool of 65 adjectives, descriptive of
      fatigue, sleepiness and related deprivation states, was developed and
      administered to 372 individuals referred by their family physicians for
      psychiatric investigation and treatment of severe insomnia. Participants attended
      one of six Canadian university-affiliated sleep clinics where they completed a
      psychiatric assessment and a 766-item questionnaire, including a number of
      standard indices of sleep-related behavior and symptoms, medical history, sleep
      hygiene, psychosocial well-being and psychopathology. Principal-components and
      item analyses were undertaken to refine the initial 65-item pool to a smaller 50
      item set, consisting of five subscales: Fatigue, Anergy, Consciousness, Energized
      and Sleepiness. Coefficient alpha was calculated and indicated high internal
      consistency reliability for all subscales. Convergent and discriminant validity
      were also evaluated by calculating correlations between FACES subscales and a
      number of independent indices. The resulting five-scale FACES questionnaire
      appears to offer a promising self-report instrument for the measurement of
      fatigue and related subjective experiences.

PMID- 12069872
TI  - Cognitive functioning in chronic fatigue syndrome and the role of depression,
      anxiety, and fatigue.
AB  - OBJECTIVE: This study was designed to investigate the role of depression,
      anxiety, and fatigue in Chronic Fatigue Syndrome (CFS) sufferers' objective and
      subjective cognitive performance. METHODS: Twenty-three CFS sufferers and 23
      healthy control participants were compared on objective and subjective
      assessments of cognitive performance. Depression, anxiety, and fatigue were also
      evaluated. RESULTS: CFS sufferers did not demonstrate any impairment in objective
      cognitive functioning compared to the control group, and objective performance
      was not related to their higher levels of depression or their level of fatigue.
      Depression scores only accounted for a small amount of the variance in CFS
      sufferers' lower subjective assessment of their cognitive performance compared to
      control participants. There were no differences between the groups on anxiety
      scores. CONCLUSION: The results are discussed in terms of the heterogeneity of
      the CFS population and the complex interaction of symptomatological factors that
      characterise CFS.

PMID- 12069873
TI  - The role of fear of physical movement and activity in chronic fatigue syndrome.
AB  - OBJECTIVE: To examine beliefs in relation to avoidance of activity in chronic
      fatigue syndrome (CFS) patients. METHODS: The first phase consisted of modifying
      an existing chronic pain measure of kinesiophobia-fear of physical movement and
      activity-and validating it on the CFS population [Tampa Scale of Kinesiophobia
      Fatigue (TSK-F); n=129; test-retest: r=.89, P<.001; alpha=.68]. Subscales of
      Illness Beliefs (alpha=.78) and Beliefs about Activity (alpha=.70) were
      identified. The second phase consisted of evaluating whether behavioural
      persistence was predicted by the TSK-F (n=33). Participants were asked to ride an
      exercise bike for as long as they felt able. RESULTS: Analyses indicated that
      behavioural persistence did not correlate with maximal heart rate or resting
      heart rate, level of tiredness, symptom severity, illness identity or emotional
      distress. However, the TSK-F did correlate highly with distance travelled and
      added a significant 15% of the variance in distance after adjustments for gender
      and physical functioning (PF). The TSK-F Beliefs about Activity subscale appears
      to be the predictive factor, explaining 12% of the variance in excise performance
      or rather 12% of the avoidance of exercise. CONCLUSION: Beliefs about Activity
      appear to be an important variable in predicting behaviour and avoidance of
      exercise. As avoidance has been suggested as a key to the maintenance of
      symptoms, disability and distress in CFS patients, this research has important
      theoretical, clinical and research implications.

PMID- 12069874
TI  - Listening to CFS: why we should pay more attention to the story of the patient.

PMID- 12069875
TI  - A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue
      scale).
AB  - OBJECTIVE: To construct an observer's rating scale sensitive to change for
      measuring severity and treatment outcome in fibromyalgia (FM) and chronic fatigue
      syndrome (CFS) patients. METHODS: A selection of items from the Comprehensive
      Psychopathological Rating Scale (CPRS) were repeatedly rated and used as outcome
      measure of a 24-week treatment study. In the study 100 women, fulfilling the
      criteria for both FM and CFS, received intermittent injections of a
      staphylococcus toxoid or placebo. Nine CPRS-items with high baseline incidence
      (cutoff 70%) were extracted and validated against global ratings and the
      Fibromyalgia Impact Questionnaire (FIQ). The fibromyalgia and chronic fatigue
      syndrome rating scale (the FibroFatigue scale) was thereafter formed based upon
      the extracted items and three supplemented ones. The interrater reliability was
      tested in 27 consecutive patients of both sexes. RESULTS: The FibroFatigue scale
      is an observer's rating scale with 12 items measuring pain, muscular tension,
      fatigue, concentration difficulties, failing memory, irritability, sadness, sleep
      disturbances, and autonomic disturbances (items derived from the CPRS) and
      irritable bowel, headache, and subjective experience of infection (new items).
      There was a statistically significant correlation between the CPRS-extracted
      items and global ratings as well as with the FIQ. The interrater reliability of
      the new scale was excellent (correlation coefficient.98), irrespective of the
      patients' gender. CONCLUSION: The FibroFatigue scale seems to be a reliable and
      valid measuring instrument with capacity to monitor symptom severity and change
      during treatment of FM/CFS patients.

PMID- 12069876
TI  - Pathogenic microbes in water and food: changes and challenges.

PMID- 12069877
TI  - Risk and control of waterborne cryptosporidiosis.
AB  - Cryptosporidium remains at the forefront of studies on waterborne disease
      transmission and abatement. The impact of environmental land use patterns which
      contribute animal and human waste, climatic precipitation leading to a strong
      association with outbreaks, and community infrastructure and water treatment are
      now recognized as contributing factors in the potential for waterborne spread of
      the protozoan. Advances in detection methodologies, including the ability to
      genotype various strains of this organism, have shown that human wastes are often
      the source of the contamination and cell culture techniques have allowed insight
      into the viability of the oocyst populations. Currently water treatment has
      focused on UV and ozone disinfection as most promising for the inactivation of
      this protozoan pathogen.

PMID- 12069878
TI  - Vibrio cholerae and cholera: out of the water and into the host.
AB  - The facultative human pathogen Vibrio cholerae can be isolated from estuarine and
      aquatic environments. V. cholerae is well recognized and extensively studied as
      the causative agent of the human intestinal disease cholera. In former centuries
      cholera was a permanent threat even to the highly developed populations of
      Europe, North America, and the northern part of Asia. Today, cholera still
      remains a burden mainly for underdeveloped countries, which cannot afford to
      establish or to maintain necessary hygienic and medical facilities. Especially in
      these environments, cholera is responsible for significant mortality and economic
      damage. During the last three decades, intensive research has been undertaken to
      unravel the virulence properties and to study the epidemiology of this
      significant human pathogen. More recently, researchers have been elucidating the
      environmental lifestyle of V. cholerae. This review provides an overview of the
      current knowledge of both the host- and environment-specific physiological
      attributes of V. cholerae.

PMID- 12069879
TI  - Antimicrobial drug resistance in Salmonella: problems and perspectives in food-
      and water-borne infections.
AB  - Strains of Salmonella spp. with resistance to antimicrobial drugs are now
      widespread in both developed and developing countries. In developed countries it
      is now increasingly accepted that for the most part such strains are zoonotic in
      origin and acquire their resistance in the food-animal host before onward
      transmission to humans through the food chain. Of particular importance since the
      early 1990s has been a multiresistant strain of Salmonella typhimurium definitive
      phage type (DT) 104, displaying resistance to up to six commonly used
      antimicrobials, with about 15% of isolates also exhibiting decreased
      susceptibility to ciprofloxacin. Mutations in the gyrA gene in such isolates have
      been characterised by a PCR LightCycler-based gyrA mutation assay, and at least
      four different mutations have been identified. Multiple resistance (to four or
      more antimicrobials) is also common in the poultry-associated pathogens
      Salmonella virchow and Salmonella hadar, with an increasing number of strains of
      these serotypes exhibiting decreased susceptibility to ciprofloxacin. Multiple
      resistance is also being found in other serotypes in several other European
      countries, and has been associated with treatment failures. For Salmonella typhi,
      multiple drug resistance is now the norm in strains originating in the Indian
      subcontinent and south-east Asia. Such multiresistant strains have been
      responsible for several epidemics and some of these have been associated with
      contaminated water supplies. Furthermore, an increasing number of multiresistant
      strains of S. typhi are now exhibiting decreased susceptibility to ciprofloxacin,
      with concomitant treatment failures. In developed countries antimicrobial
      resistance in zoonotic salmonellas has been attributed to the injudicious use of
      antimicrobials in food-producing animals. It is hoped that the application of
      Codes of Practice for the use of such agents, which have been prepared by the
      pharmaceutical industry in response to widespread international concern about the
      development of drug resistance in bacterial pathogens, will now result in a
      widespread reduction in the incidence of drug-resistant salmonellas in food
      production animals and humans on an international scale.

PMID- 12069880
TI  - Legionella pneumophila: an aquatic microbe goes astray.
AB  - Legionella pneumophila is naturally found in fresh water were the bacteria
      parasitize within protozoa. It also survives planctonically in water or biofilms.
      Upon aerosol formation via man-made water systems, L. pneumophila can enter the
      human lung and cause a severe form of pneumonia, called Legionnaires' disease.
      The pathogenesis of Legionnaires' disease is largely due to the ability of L.
      pneumophila to invade and grow within macrophages. An important characteristic of
      the intracellular survival strategy is the replication within the host vacuole
      that does not fuse with endosomes or lysosomes. In recent times a great number of
      bacterial virulence factors which affect growth of L. pneumophila in both
      macrophages and protozoa have been identified. The ongoing Legionella genome
      project and the use of genetically tractable surrogate hosts are expected to
      significantly contribute to the understanding of bacterium-host interactions and
      the regulation of virulence traits during the infection cycle. Since person-to
      person transmission of legionellosis has never been observed, the measures for
      disease prevention have concentrated on eliminating the pathogen from water
      supplies. In this respect detection and analysis of Legionella in complex
      environmental consortia become increasingly important. With the availability of
      new molecular tools this area of applied research has gained new momentum.

PMID- 12069881
TI  - Enterococci from foods.
AB  - Enterococci have recently emerged as nosocomial pathogens. Their ubiquitous
      nature determines their frequent finding in foods as contaminants. In addition,
      the notable resistance of enterococci to adverse environmental conditions
      explains their ability to colonise different ecological niches and their
      spreading within the food chain through contaminated animals and foods.
      Enterococci can also contaminate finished products, such as fermented foods and,
      for this reason, their presence in many foods (such as cheeses and fermented
      sausages) can only be limited but not completely eliminated using traditional
      processing technologies. Enterococci are low grade pathogens but their intrinsic
      resistance to many antibiotics and their acquisition of resistance to the few
      antibiotics available for treatment in clinical therapy, such as the
      glycopeptides, have led to difficulties and a search for new drugs and
      therapeutic options. Enterococci can cause food intoxication through production
      of biogenic amines and can be a reservoir for worrisome opportunistic infections
      and for virulence traits. Clearly, there is no consensus on the acceptance of
      their presence in foodstuffs and their role as primary pathogens is still a
      question mark. In this review, the following topics will be covered: (i)
      emergence of the enterococci as human pathogens due to the presence of virulence
      factors such as the production of adhesins and aggregation substances, or the
      production of biogenic amines in fermented foods; (ii) their presence in foods;
      (iii) their involvement in food-borne illnesses; (iv) the presence, selection and
      spreading of antibiotic-resistant enterococci as opportunistic pathogens in
      foods, with particular emphasis on vancomycin-resistant enterococci.

PMID- 12069882
TI  - The role of iron in Campylobacter gene regulation, metabolism and oxidative
      stress defense.
AB  - Enteric Campylobacter species cause gastrointestinal diseases in humans. Like
      almost all organisms, campylobacters have an absolute requirement for iron, but
      are faced with variable availability of iron in the environment and host tissues.
      Campylobacters have developed mechanisms to scavenge sufficient iron for
      metabolism and growth. However, iron also participates in the formation of
      reactive oxygen species, and this forces pathogens to maintain intracellular iron
      homeostasis and to cope with oxidative stresses. The presence of two separate,
      but possibly overlapping iron-responsive regulatory systems, which regulate iron
      acquisition and oxidative stress defense, and the presence of genes encoding
      multiple iron acquisition and detoxification systems in Campylobacter indicate
      the central role that iron plays in Campylobacter gene regulation and virulence.

PMID- 12069883
TI  - Foodborne viruses.
AB  - Foodborne and waterborne viral infections are increasingly recognized as causes
      of illness in humans. This increase is partly explained by changes in food
      processing and consumption patterns that lead to the worldwide availability of
      high-risk food. As a result, vast outbreaks may occur due to contamination of
      food by a single foodhandler or at a single source. Although there are numerous
      fecal-orally transmitted viruses, most reports of foodborne transmission describe
      infections with Norwalk-like caliciviruses (NLV) and hepatitis A virus (HAV),
      suggesting that these viruses are associated with the greatest risk of foodborne
      transmission. NLV and HAV can be transmitted from person to person, or indirectly
      via food, water, or fomites contaminated with virus-containing feces or vomit.
      People can be infected without showing symptoms. The high frequency of secondary
      cases of NLV illness and - to a lesser extent - of hepatitis A following a
      foodborne outbreak results in amplification of the problem. The burden of illness
      is highest in the elderly, and therefore is likely to increase due to the aging
      population. For HAV, the burden of illness may increase following hygienic
      control measures, due to a decreasing population of naturally immune individuals
      and a concurrent increase in the population at risk. Recent advances in the
      research of NLV and HAV have led to the development of molecular methods which
      can be used for molecular tracing of virus strains. These methods can be and have
      been used for the detection of common source outbreaks. While traditionally
      certain foods have been implicated in virus outbreaks, it is clear that almost
      any food item can be involved, provided it has been handled by an infected
      person. There are no established methods for detection of viruses in foods other
      than shellfish. Little information is available on disinfection and preventive
      measures specifically for these viruses. Studies addressing this issue are
      hampered by the lack of culture systems. As currently available routine
      monitoring systems exclusively focus on bacterial pathogens, efforts should be
      made to combine epidemiological and virological information for a combined
      laboratory-based rapid detection system for foodborne viruses. With better
      surveillance, including typing information, outbreaks of foodborne infections
      could be reported faster to prevent further spread.

PMID- 12069884
TI  - Microbiological safety of natural mineral water.
AB  - Natural mineral water originates from groundwater, an oligotrophic ecosystem
      where the level of organic matter is low and of a very limited bioavailability.
      The bacterial populations that evolve in these ecosystems are heterotrophic and
      in starvation-survival state resulting from an insufficient amount of nutrients;
      for this reason they enter a viable but non-culturable state. After bottling, the
      number of viable counts increases rapidly, attaining 10(4)-10(5) colony-forming
      units ml(-1) within 3-7 days. These bacterial communities, identified by culture
      or with specific probes, are primarily aerobic, saprophytic, Gram-negative rods.
      Groundwater sources for natural mineral waters are selected such that they are
      not vulnerable to fecal contamination. Ecological data, especially the diversity
      and physiological properties of bacterial communities, are essential together
      with epidemiological studies in order to perform a risk analysis for natural
      mineral waters. On a continuing basis, the management of microbial risks has to
      rely on assessment of the heterotrophic plate count and, more specially, on
      detection of marker organisms, i.e. the classic fecal contamination indicators
      that have to be absent, and vulnerability indicators for which the occurrence
      should be as low as possible. It is also recommended to search regularly, but not
      routinely, for viral and protozoan pathogens.

PMID- 12069885
TI  - Methods for detection and visualization of intracellular polymers stored by
      polyphosphate-accumulating microorganisms.
AB  - Polyphosphate-accumulating microorganisms (PAOs) are important in enhanced
      biological phosphorus (P) removal. Considerable effort has been devoted to
      understanding the biochemical nature of enhanced biological phosphorus removal
      (EBPR) and it has been shown that intracellular polymer storage plays an
      important role in PAO's metabolism. The storage capacity of PAOs gives them a
      competitive advantage over other microorganisms present that are not able to
      accumulate internal reserves. Intracellular polymers stored by PAOs include
      polyphosphate (poly-P), polyhydroxyalkanoates (PHAs) and glycogen. Staining
      procedures for qualitative visualization of polymers by optical microscopy and
      combinations of these procedures with molecular tools for in situ identification
      are described here. The strengths and weaknesses of widely used polymer
      quantification methods that require destruction of samples, are also discussed.
      Finally, the potential of in vivo nuclear magnetic resonance (NMR) spectroscopy
      for on-line measurement of intracellular reserves is reported.

PMID- 12069886
TI  - Intercenter reproducibility of binary typing for Staphylococcus aureus.
AB  - The reproducibility of the binary typing (BT) protocol developed for
      epidemiological typing of Staphylococcus aureus was analyzed in a biphasic
      multicenter study. In a Dutch multicenter pilot study, 10 genetically unique
      isolates of methicillin-resistant S. aureus (MRSA) were characterized by the BT
      assay as presented by van Leeuwen et al. [J. Clin. Microbiol. 2001 39 (1) 328].
      The BT assay, including a standardized DNA extraction protocol was performed in
      duplicate in eleven medical microbiology laboratories. Two different
      hybridization detection procedures were applied and a prelabeled DNA sample as
      process control was included. Only three laboratories accurately identified all
      strains. Divergence in technical procedures resulted in misinterpretation due to
      an increasing number of faint or absent hybridization signals in combination with
      high background staining. The binary type of the process control was determined
      correctly by all participating laboratories. The feasibility of the BT protocol
      was related directly to the skill of the laboratory personnel. On the basis of
      the national study, we concluded that the DNA extraction protocol needed
      modification to improve DNA yield and purity. Subsequently, seven European
      laboratories participated in an international study to determine the
      reproducibility of the modified BT protocol. Each center was asked to analyze 10
      DNA samples previously extracted from 10 MRSA strains (phase 1) and,
      additionally, to analyze 10 MRSA strains, using the standardized or their in
      house DNA isolation protocol (phase 2). A prelabeled DNA process control sample
      was included again. The binary types of all DNA samples were identified correctly
      by all but one laboratories. This latter laboratory diverged from the protocol by
      adding an excess of labeled DNA to the hybridization mixture, resulting in a high
      background and, therefore, noninterpretable BT results. All centers produced
      identical BT results for the process control. Five of the seven centers correctly
      identified the binary types of all 10 MRSA strains in phase 2 of the
      international study. Three of these centers used their in-house DNA extraction
      protocol. Divergence from the standard BT protocol in the remaining two centers
      resulted in no interpretable BT data for the 10 MRSA strains. The study
      demonstrated that each center that followed the BT protocol to the letter could
      generate reproducible results, irrespective whether or not an in-house DNA
      isolation protocol was used. The current BT protocol thus represents a simple
      method generating robust, reproducible genotype data for S. aureus strains.

PMID- 12069887
TI  - Preparation and characterization of Cryptococcus neoformans synchronous culture.
AB  - We have developed a method for preparation of synchronous culture in Cryptococcus
      neoformans. The method is based on age fractionation of exponentially growing
      asynchronous culture through differential sedimentation in 10-20% (w/v) lactose
      gradient. C. neoformans capsule thickness should be reduced to a minimum to
      ensure most accurate age fractionation, which is necessary to obtain a higher
      degree of synchrony. The C. neoformans synchronous culture system has revealed
      important characteristics with respect to cellular morphology, DNA content and
      cell volume distribution. The method can be used for further cell cycle studies.

PMID- 12069888
TI  - Flow cytometric evaluation of adhesion of Streptococcus pyogenes to epithelial
      cells.
AB  - The precise roles of various surface molecules in the attachment of Streptococcus
      pyogenes to host epithelia are currently unclear. A flow cytometry assay that
      facilitates the analysis of the kinetics of S. pyogenes adhesion to epithelial
      cells was developed. Dose- and time-dependent adhesion isotherms with both buccal
      epithelial cells (BECs) and Hep-2 cells as substrata were obtained. Although
      binding equilibrium is reached within 2 h on both cell types, saturation of
      binding sites on BECs is not achieved within a wide range of experimental
      conditions. This indicates a high degree of non-specific attachment to that cell
      type. Since no rinsing step is necessary when using flow cytometry to analyze
      adhesion, low-affinity associations were observable. This was confirmed by
      determining bacterial desorption rates early and late in the adsorption process.
      Binding irregularities were also easily detected since the cytometer records and
      displays data for up to 10,000 epithelial cells per time point. It is proposed to
      use this methodology to assign roles to particular surface
      molecules/characteristics during distinct phases of adhesion.

PMID- 12069889
TI  - Phage display as a novel screening method to identify extracellular proteins.
AB  - Extracellular proteins are involved in many diverse and essential cell functions
      and in pathogenic bacteria, and they may also serve as virulence factors.
      Therefore, there is a need for methods that identify the genes encoding this
      group of proteins in a bacterial genome. Here, we present such a method based on
      the phage display technology. A novel gene III-based phagemid vector, pG3DSS, was
      constructed that lacks the signal sequence which normally orientates the encoded
      fusion protein to the Escherichia coli cell membrane, where it is assembled into
      the phage particle. When randomly fragmented DNA is inserted into this vector,
      only phagemids containing an insert encoding a signal sequence will give rise to
      phage particles displaying a fusion protein. These phages also display an E-tag
      epitope in fusion with protein III, which enables isolation of phages displaying
      a fusion protein, using antibodies against the epitope. From a library
      constructed from Staphylococcus aureus chromosomal DNA, genes encoding secreted
      as well as transmembrane proteins were isolated, including adhesins, enzymes and
      transport proteins.

PMID- 12069890
TI  - Detection of aminotransferase activity of Propionibacterium freudenreichii after
      SDS-PAGE.
AB  - Aminotransferases (ATs) had previously been detected after native
      electrophoresis. We show now that aminotransferase(s) of Propionibacterium
      freudenreichii can be detected after sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Moreover, it retained a high activity (84%) in the
      presence of 0.23% SDS, contrary to what was observed for aminotransferase(s) of
      Bifidobacterium bifidum (54%) and of six other cheese-related species (0-20%).

PMID- 12069891
TI  - Design and development of a novel genetic probe for the analysis of repressor
      operator interactions.
AB  - While the native diphtheria tox promoter/operator (toxPO)-lacZ transcriptional
      fusion has allowed initial isolation and characterization of the diphtheria toxin
      repressor (DtxR), the low level of reporter gene expression has limited the
      detection and analysis of mutations affecting subtle changes in repressor
      operator binding. In order to overcome this difficulty, we have constructed a
      novel hybrid promoter/operator-lacZ transcriptional fusion in which the "-35" and
      spacing of the tac promoter was fused to the "-10" and interrupted palindromic
      sequence of toxO. We show that the hybrid tacPtoxO is regulated by the transition
      metal ion-dependent DtxR and that lacZ expression is increased approximately 70
      fold in the reporter strain Escherichia coli DH5alpha/lambdaRS45-tacPtoxO-lacZ
      relative to DH5alpha/lambdaRS45-toxPO-lacZ. In addition, we have constructed a
      transcriptional fusion between tacPtoxO and luc, pJL1. We have used pJL1 to
      program S30 extracts of E. coli in order to direct in vitro the coupled
      transcription and translation of luciferase. We demonstrate the utility of this
      in vitro system in providing a direct functional link between in vivo and in
      vitro observations with DtxR and mutants of DtxR, which display subtle changes in
      activity in a manner not previously possible.

PMID- 12069892
TI  - In vivo NMR system for evaluating oxygen-dependent metabolic status in microbial
      culture.
AB  - To optimize an appropriate microbial culture in a fermentor, precise control of
      the medium's dissolved oxygen tension (DOT) is crucial. In particular, to study
      the effect of DOT on cellular metabolic status by using in vivo nuclear magnetic
      resonance (NMR) measurements, the set-up of the experiment must be optimized to
      maintain DOT in the culture. In the conventional method, DOT is monitored by a
      sensor inside a fermentor and is controlled by changing the agitation rate. Here,
      we report a novel and accurate system that minimizes time lag by an automated
      aeration flow control device, allowing an NMR spectrometer to monitor
      representative metabolites in real-time. To fulfill these two objects, the
      fermentor was composed of a fermentation vessel and two outer tubes, through
      which the medium was circulated by rotary pumps. One tube monitored DOT in via a
      sensor, and at the same time the other tube monitored metabolites via an NMR
      spectrometer. In this study, we used this system to analyze the responses of
      Escherichia coli cells under various oxygen conditions. The results validated the
      use of this system in the study of microbial metabolism.

PMID- 12069893
TI  - Significance of electrophoretic mobility distribution to bacterial transport in
      granular porous media.
AB  - A method is developed to obtain the electrophoretic mobility distribution of
      colloidal particles by microelectrophoresis. The results demonstrate that for
      small particles (< 1 microm), the experimental mobility distribution must be
      deconvoluted to remove the effect of the random Brownian motion so that the
      electrophoretic mobility distribution can be obtained. For bacteria-sized
      particles (on the order of 1 microm or larger), the random Brownian motion is not
      significant, and the experimental mobility distribution represents the
      electrophoretic mobility distribution. The significance of the electrophoretic
      mobility distribution to bacterial transport is demonstrated through comparison
      between experimental and theoretical values of collision efficiency. Using the
      extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, the electrophoretic
      mobility distribution of bacteria is transformed to the distribution of collision
      efficiencies. For strain Comamonas sp. DA001, the predicted collision efficiency
      values span orders of magnitude, indicating that variation of surface charge
      density in a monoclonal bacterial population is a cause for the orders of
      magnitude variation of experimentally determined collision efficiencies. However,
      despite the fact that the predicted and experimental alpha distributions overlap,
      the match is not adequate. This inadequacy is ascribed to inability to probe
      heterogeneity of bacterial surface hydrophobicity, and the inability of the DLVO
      theory to quantitatively model particle deposition.

PMID- 12069894
TI  - Trace analysis of muramic acid in indoor air using an automated derivatization
      instrument and GC-MS(2) or GC-MS(3).
AB  - An automated derivatization instrument has been developed for the preparation of
      alditol acetates from bacterial hydrolysates for analysis by gas chromatography
      mass spectrometry (GC-MS). The current report demonstrates the utility of the
      automated instrument for the more demanding task of trace analysis of muramic
      acid (Mur) in airborne dust using gas chromatography-tandem mass spectrometry (GC
      MS(2)). Conditions for efficient derivatization of Mur, vital for trace analysis,
      are rigorous including lactam and imido group formation under anhydrous
      conditions. Furthermore, as the detection limit is lowered, possible
      contamination or carry-over of samples becomes an increasingly greater
      consideration and must not occur. The instrument meets these criteria and was
      successfully used for assaying the levels of Mur in laboratory air, which were
      found to be much lower than in the previous studies of heavily occupied schools
      and agricultural environments. The potential for GC-MS(3) in further lowering the
      detection limit was also demonstrated.

PMID- 12069895
TI  - Detection, with a pH indicator, of bacterial mutants unable to denitrify.
AB  - In order to facilitate isolation of mutants with alterations in the
      denitrification pathway, a new screening procedure using phenol red incorporated
      into agar overlay has been defined. Alkalinization in the neighbourhood of
      denitrifying colonies respiring nitrate or nitrite gives rise to a red circular
      halo. Antimycin blocked these colour changes, which suggests their association
      with the periplasmic reduction of nitrite. Inhibition of nitrous oxide reductase
      by acetylene had no significant effect on alkalinization elicited by nitrate or
      nitrite. Several mutants negative by the phenol red staining test were generated
      by transposon Tn5 mutagenesis of Paracoccus denitrificans. All these mutants were
      defective in the activities of nitrite and nitric oxide reductases while the
      other denitrification activities were present at the wild-type level.

PMID- 12069896
TI  - Evaluation of gene-technological and conventional methods in the identification
      of Streptococcus pneumoniae.
AB  - To find reliable methods able to identify the "difficult" Streptococcus
      pneumoniae isolates, an in-house polymerase chain reaction (PCR) for pneumolysin
      gene (Ply-PCR) and a commercial RNA hybridisation test (AccuProbe) were
      evaluated. Selected isolates of suspected pneumococci, sent for confirmation of
      identification and for serotyping, were classified into four groups based on
      their optochin sensitivity and capsule reaction. All isolates in Group 1, which
      consisted of 24 typical, optochin-sensitive, encapsulated pneumococcal strains,
      were positive in the Ply-PCR and AccuProbe tests. In Group 2, which consisted of
      25 optochin-sensitive, but unencapsulated pneumococcal strains, all the isolates
      were positive in the Ply-PCR test, and 23 were positive in the AccuProbe test. In
      Group 3, which consisted of 15 atypical, optochin-resistant but encapsulated
      pneumococci, 12 of the isolates were positive in the Ply-PCR and 12 in the
      AccuProbe test, and 11 of these 12 strains were positive in both tests. In Group
      4, which consisted of 36 equivocal optochin-resistant, unencapsulated isolates,
      15 strains were positive in the Ply-PCR test and 8 strains in the AccuProbe test.
      As a conclusion, the Ply-PCR and AccuProbe tests identified similarly typical
      optochin-sensitive pneumococci, but gave partly controversial results about
      atypical pneumococci. Thus, they did not reliably help in the identification of
      suspected pneumococcal isolates lacking the conventional characteristics of
      pneumococcus.

PMID- 12069897
TI  - Bacterial DNA decontamination for reverse transcription polymerase chain reaction
      (RT-PCR).
AB  - For RT-PCR, removal of contaminating genomic DNA in RNA samples using manganese
      sulfate was more effective than magnesium. DNA contamination was removed in 3
      microg of nucleic acid using 10 U of RNase-free DNase I in 10-microl reaction
      volumes. The digestion procedure was compatible with commercial RNA extraction
      kits and was suitable for RT-PCR assay.

PMID- 12069898
TI  - Vanilloid and TRP channels: a family of lipid-gated cation channels.
AB  - The emergence of the TRP (C) and vanilloid (TRPV) receptor family of Ca(2+)
      permeable channels has started to provide molecular focus to a linked group of
      ion channels whose common feature is activation primarily by intracellular
      ligands. These channels have a central role in Ca(2+) homeostasis in virtually
      all cells and in particular those that lack voltage-gated Ca(2+) channels. We
      will discuss recent work that is more precisely defining both molecular form and
      physiological function of this important group of Ca(2+) permeable channels with
      particular focus on the intracellular ligands that gate and modulate channel
      activity.

PMID- 12069899
TI  - Characterisation of the effects of ATPA, a GLU(K5) receptor selective agonist, on
      excitatory synaptic transmission in area CA1 of rat hippocampal slices.
AB  - Kainate receptors are involved in a variety of synaptic functions in the CNS
      including the regulation of excitatory synaptic transmission. Previously we
      described the depressant action of the GLU(K5) selective agonist (RS)-2-amino-3
      (3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA) on synaptic
      transmission in the Schaffer collateral-commissural pathway of rat hippocampal
      slices. In the present study we report several new features of the actions of
      ATPA at this synapse. Firstly, the effectiveness of ATPA is developmentally
      regulated. Secondly, the effects of ATPA decline during prolonged or repeated
      applications. Thirdly, the effects of ATPA are not mediated indirectly via
      activation of GABA(A), GABA(B), muscarinic or adenosine A(1) receptors. Fourthly,
      elevating extracellular Ca(2+) from 2 to 4 mM antagonises the effects of ATPA.
      Some differences between the actions of ATPA and kainate on synaptic transmission
      in the Schaffer collateral-commissural pathway are also noted.

PMID- 12069901
TI  - Mechanisms of GABA(A) receptor blockade by millimolar concentrations of
      furosemide in isolated rat Purkinje cells.
AB  - The action of diuretic furosemide on the GABA(A) receptor was studied in acutely
      isolated Purkinje cells using the whole-cell recording and fast application
      system. Furosemide blocked stationary component of GABA-activated currents in a
      concentration-dependent manner with IC(50) value > 5 mM at -70 mV. The inhibition
      was rapid in the onset, fully reversible and did not require drug pre-perfusion.
      The termination of GABA and furosemide co-application was followed by transient
      increase in the inward current 'tail' current, which was not observed when
      furosemide was continuously present in the solution. The degree of furosemide
      block did not depend on GABA concentration. Furosemide block increased with
      membrane depolarization. Five millimolar furosemide depressed GABA currents by
      32.4+/-1.3% at -70 mV and by 76.7+/-5.0% at +70 mV. Analysis of the voltage
      dependence of the block suggests that furosemide binds at the site located within
      GABA(A) channel pore with a dissociation constant of 5.3+/-0.5 mM at 0 mV and
      electric distance of 0.27. Our results provide evidence that furosemide interacts
      with Purkinje cell GABA(A) receptors (most probably composed of
      alpha1beta2/3gamma2 subunits) through a low affinity site located in channel pore
      and suggest that furosemide acts as a sequential open channel blocker, which
      prevents the dissociation of agonist while the channel is blocked.

PMID- 12069902
TI  - A histidine residue in the extracellular N-terminal domain of the GABA(A)
      receptor alpha5 subunit regulates sensitivity to inhibition by zinc.
AB  - The divalent cation zinc is abundant in the brain, particularly in the mossy
      fibers of the hippocampus. Recent evidence suggests that zinc is packaged into
      some synaptic vesicles in this region and can be co-released with
      neurotransmitter. Zinc inhibits the activity of GABA(A) receptors and the
      sensitivity of the receptor to zinc is influenced by its alpha subunit subtype
      composition. The alpha4, alpha5 and alpha6 subunits confer greater sensitivity to
      zinc than receptors containing other alpha subunits. The alpha4 and alpha5
      subunits are highly expressed in hippocampal neurons, and likely mediate any
      effects of zinc on GABAergic neurotransmission in this area. The alpha5 subunit
      contains a unique histidine residue in the N-terminal extracellular domain while
      the other alpha subunits have an aspartate residue in this location. Point
      mutations were created to exchange the histidine and aspartate residues of the
      alpha1 and alpha5 subunits. Receptors containing the mutated alpha5((H195D))
      subunit had reduced sensitivity to zinc, while alpha1((D191H))beta3gamma2L
      receptors had increased sensitivity to zinc, similar to the alpha5beta3gamma2L
      wild type receptors. These findings indicate that histidine195 of the alpha5
      subunit plays an important role in determining the sensitivity of recombinant
      GABA(A) receptors to zinc.

PMID- 12069900
TI  - Neurotrophins induce BDNF expression through the glutamate receptor pathway in
      neocortical neurons.
AB  - Neurotrophins jointly exert various functions in the nervous system, including
      neuronal differentiation, survival, and regulation of synaptic plasticity.
      However, the functional interactions of neurotrophins or mechanisms through which
      neurotrophins regulate each other are still not clear. In the present study,
      brain-derived neurotrophic factor (BDNF) mRNA expression is induced by
      neurotrophin-4/5 (NT-4/5) and by BDNF itself in neocortical neurons. K252a, a
      specific tyrosine kinase (Trk) inhibitor, completely suppresses BDNF- and NT-4/5
      enhanced BDNF mRNA expression. NT-4/5 significantly augments BDNF protein
      production, which is also reversed by K252a. When neurons are incubated with
      neurotrophin-3 (NT-3) or nerve growth factor (NGF), there are no significant
      changes in BDNF mRNA or protein expression. Interestingly, the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor blocker 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX) or the N-methyl-D-aspartate (NMDA) receptor
      blocker AP-5 completely suppresses NT-4/5-enhanced BDNF protein production, while
      tetrodotoxin (TTX) only suppresses NT-4/5-enhanced BDNF production by 50%.
      Additionally, the mitogen activated protein (MAP) kinase inhibitor PD98059
      enhances BDNF-induced glutamate receptor-1 (GluR1) protein expression, but a
      phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 strongly reduces BDNF
      induced GluR1 protein expression. Taken together, glutamate receptors are
      important for the regulation of BDNF expression by neurotrophins, and MAP and
      PI3K kinases differentially modulate AMPA receptor expression in the cortical
      neurons.

PMID- 12069903
TI  - Molecular cloning and pharmacology of functionally distinct isoforms of the human
      histamine H(3) receptor.
AB  - The pharmacology of histamine H(3) receptors suggests the presence of distinct
      receptor isoforms or subtypes. We herein describe multiple, functionally
      distinct, alternatively spliced isoforms of the human H(3) receptor.
      Combinatorial splicing at three different sites creates at least six distinct
      receptor isoforms, of which isoforms 1, 2, and 4, encode functional proteins.
      Detailed pharmacology on isoforms 1 (unspliced receptor), and 2 (which has an 80
      amino acid deletion within the third intracellular loop of the protein) revealed
      that both isoforms displayed robust responses to a series of known H(3) agonists,
      while all agonists tested displayed increased potency at isoform 2 relative to
      isoform 1. Histamine, N(alpha)-methylhistamine, and R(-) and S(+)-alpha
      methylhistamine are 16-23-fold more potent, while immepip and imetit are three to
      fivefold more potent. Antagonist experiments revealed a rank order of potency at
      both isoforms of clobenpropit>iodophenpropit>thioperamide, and these drugs are
      fivefold less potent at isoform 2 than isoform 1. To further explore the
      pharmacology of H(3) receptor function, we screened 150 clinically relevant
      neuropsychiatric drugs for H(3) receptor activity, and identified a small number
      of antipsychotics that possess significant antagonist activity.

PMID- 12069904
TI  - Decreased G-protein coupling of serotonin 5-HT(1A) receptors in the brain of 5
      HT(1B) knockout mouse.
AB  - The firing of central serotonin (5-hydroxytryptamine, 5-HT) neurons and their
      capacity to release 5-HT are subjected to a receptor-mediated auto-control via 5
      HT(1A) and 5-HT(1B) receptors respectively located on the somata/dendrites (5
      HT(1A) autoreceptors) and preterminal axon arborizations (5-HT(1B) autoreceptors)
      of these neurons. To further characterize mutual adaptations of these two
      receptor subtypes in the absence of one of them, activation of G-protein coupling
      by agonist was measured and compared to wild-type (WT) in 5-HT(1A) and 5-HT(1B)
      homozygous knockout (KO) mice. As expected, in WT, the non-selective 5-HT(1A/1B)
      receptor agonist 5-carboxyamidotryptamine (5-CT) stimulated guanosine 5'-O-(gamma
      [(35)S]thio)triphosphate ([(35)S]GTP(gamma)S) incorporation in many brain regions
      endowed with one and/or the other receptor. In the respective KOs, no stimulation
      was measured in regions known to express only or mainly the deleted receptor. In
      the 5-HT(1A) KOs, the amplitude of G-protein activation in regions endowed with 5
      HT(1B) receptors was unchanged by comparison to WT. In the 5-HT(1B) KOs, the
      magnitude of the 5-CT stimulation was the same as WT in all regions containing 5
      HT(1A) receptors, except in the amygdala, where it was significantly lower, even
      if this region was one of the most strongly activated in the WT. A similar result
      was obtained in the amygdala of 5-HT(1B) KOs after activation by the selective 5
      HT(1A) receptor agonist R-(+)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT).
      Under these conditions, however, there was in addition a significant lowering of
      the stimulated (but not basal) [(35)S]GTP(gamma)S incorporation by comparison to
      WT in all regions endowed with 5-HT(1A) receptors, including the dorsal raphe
      nucleus. Thus, eventhough agonist radioligand binding to either 5-HT(1A) or 5
      HT(1B) receptors is unchanged in the reciprocal KOs, it appears that a
      compensatory decrease in the efficiency of G-protein coupling to 5-HT(1A)
      receptors has developed in the 5-HT(1B) mutant. This could represent the first
      indication of a cross-talk between these two 5-HT receptor subtypes, at least in
      brain regions where they are co localized in the same neurons.

PMID- 12069905
TI  - Adenovirus-mediated G(alpha)(q)-protein antisense transfer in neurons replicates
      G(alpha)(q) gene knockout strategies.
AB  - Antisense approaches are increasingly used to dissect signaling pathways linking
      cell surface receptors to intracellular effectors. Here we used a recombinant
      adenovirus to deliver G-protein alpha(q) antisense into rat superior cervical
      ganglion (SCG) neurons and neuronal cell lines to dissect G(alpha)(q)-mediated
      signaling pathways in these cells. This approach was compared with other
      G(alpha)(q) gene knockdown strategies, namely, antisense plasmid and knockout
      mice. Infection with adenovirus expressing G(alpha)(q) antisense (G(alpha)(q)AS
      AdV) selectively decreased immunoreactivity for the G(alpha)(q) protein.
      Expression of other G(alpha) protein subunits, such as G(alpha)(oA/B,) was
      unaltered. Consistent with this, modulation of Ca(2+) currents by the G(alpha)(q)
      coupled M(1) muscarinic receptor was severely impaired in neurons infected with
      G(alpha)(q)AS AdV whereas modulation via the G(alpha)(oA)-coupled M(4) muscarinic
      receptor was unchanged. In agreement, activation of phospholipase C and
      consequent mobilization of intracellular Ca(2+) by UTP receptors was lost in
      NG108-15 cells infected with G(alpha)(q)AS AdV but not in cells infected with the
      control GFP-expressing adenovirus. Results obtained with this recombinant AdV
      strategy qualitatively and quantitatively replicated results obtained using SCG
      neurons microinjected with G(alpha)(q) antisense plasmids or SCG neurons from
      G(alpha)(q) knockout mice. This combined antisense/recombinant adenoviral
      approach can therefore be useful for dissecting signal transduction mechanisms in
      SCG and other neurons.

PMID- 12069906
TI  - Imidazoline(2) (I(2)) binding site- and alpha(2)-adrenoceptor-mediated modulation
      of central noradrenergic and HPA axis function in control rats and chronically
      stressed rats with adjuvant-induced arthritis.
AB  - The aim of this study was to investigate imidazoline(2) (I(2)) binding site- and
      alpha(2)-adrenoceptor-mediated control of central noradrenergic and HPA axis
      activity in control rats and chronically stressed rats with adjuvant-induced
      arthritis (AA). Basal levels of extracellular nonadrenaline (NA) in the region of
      the hypothalamic paraventricular nucleus (PVN) of AA rats were significantly
      greater than controls. Both the I(2) binding site selective ligand BU224 (10 mg
      kg(-1) i.p.) and the alpha(2)-adrenoceptor antagonist RX821002 (2.5 mg kg(-1)
      i.p.) significantly elevated extracellular levels of NA in the PVN region and
      plasma corticosterone (CORT) in a rapid and transient manner in both control and
      AA rats. The noradrenergic response of AA rats to BU224 was significantly
      enhanced compared with drug treated controls. There was a significant correlation
      between extracellular NA in the PVN region and plasma CORT following BU224 and
      RX821002. In conclusion, central noradrenergic and HPA axis activity in control
      and chronically stressed AA rats appear to be under the control of both I(2)
      binding sites and alpha(2)-adrenoceptors. Increased basal levels of extracellular
      NA in the PVN region of AA rats suggests increased noradrenergic activity in
      these animals which is modulated to a greater extent by I(2) binding sites than
      by alpha(2)-adrenoceptors.

PMID- 12069907
TI  - The effect of cannabinoids on capsaicin-evoked calcitonin gene-related peptide
      (CGRP) release from the isolated paw skin of diabetic and non-diabetic rats.
AB  - Sensory neural dysfunction is common in patients with peripheral neuropathy, a
      major complication of diabetes mellitus. In animal models of inflammatory and
      neuropathic pain cannabinoids potently attenuate pain behaviour, cannabinoid (CB)
      receptors located on nociceptive primary afferent neurones being important in
      their anti-hyperalgesic actions. A key measure of sensory neurone function is
      stimulus-evoked neuropeptide release. We investigated the effect of cannabinoid
      on capsaicin-evoked release of calcitonin gene-related peptide (CGRP) from the
      rat paw skin in vitro, comparing non-diabetic and streptozotocin-induced diabetic
      animals. Diabetes caused a greater than two-fold increase in basal and capsaicin
      evoked CGRP release. The synthetic CB(1)/CB(2) receptor agonist, CP55940 (100
      nM), inhibited capsaicin-evoked CGRP release in both non-diabetic (30.92+/-7.69%,
      P<0.05) and diabetic animals (37.82+/-9.85%, P<0.05). The CB(1) receptor
      antagonist SR141716A (100 nM), but not the CB(2) receptor antagonist SR144528
      (100 nM), significantly attenuated the inhibitory action of CP55940. The
      endogenous cannabinoid, anandamide (100 nM) inhibited capsaicin-evoked CGRP
      release in non-diabetic animals (28.88+/-7.12%, P<0.05) but neither the CB(1) nor
      the CB(2) receptor antagonist attenuated this action of anandamide. Anandamide
      (100 nM) did not significantly inhibit capsaicin-evoked CGRP release from the paw
      skin of diabetic animals, but it did produce a small stimulation of CGRP release
      at high concentrations (10 microM). These data suggest that peripheral CB(1)
      receptors mediate inhibition of capsaicin-evoked neuropeptide release from the
      paw skin of both non-diabetic and diabetic animals. However, pathological changes
      in the diabetic animals appear to preclude the non-CB(1) receptor mediated
      inhibitory action of the endogenous cannabinoid, anandamide.

PMID- 12069908
TI  - Intravenous cocaine-induced activity in A/J and C57BL/6J mice: behavioral
      sensitization and conditioned activity.
AB  - The stimulant properties of cocaine have been extensively investigated in the
      mouse using either intraperitoneal (i.p.) or subcutaneous (s.c.) administration
      of drug. However, cocaine use in humans often involves intravenous (i.v.)
      administration of drug. The purpose of this study was to develop a methodology
      for studying i.v. cocaine-induced activity in the mouse, which allows within
      session determination of the dose-response function, and assessment of the
      development of behavioral sensitization and conditioned activity. The stimulant
      effects of i.v. cocaine (3-25 mg/kg) were investigated in C57BL/6J and A/J mice
      both acutely and following repeated treatments (four treatments at 48 hour
      intervals), in addition to the conditioned activating properties of the cocaine
      paired context. Cocaine produced a dose-dependent increase in measures of motor
      activity in both strains of mice. Repeated cocaine treatments resulted in the
      development of behavioral sensitization to the stimulant properties of the drug
      at all doses tested, and exposure to the cocaine-paired context in the absence of
      drug revealed the development of conditioned activity. While both C57BL/6J and
      A/J strains displayed these phenomena, differences were observed between
      ambulation and total beam breaks, highlighting differences between multiple
      behavioral end-points. Both strains of mice displayed conditioned activity of a
      higher magnitude than their response to novelty, in addition to a positive
      relationship between the number of drug-environment pairings and the magnitude of
      the conditioned response. In summary, these data extend to the i.v. route of
      administration previous observations on cocaine-induced activity and conditioned
      activity.

PMID- 12069909
TI  - CompB (J-113397), selectively and competitively antagonizes nociceptin activation
      of inwardly rectifying K(+) channels in rat periaqueductal gray slices.
AB  - A novel opioid receptor family, the nociceptin/orphanin FQ (N/OFQ) peptide (NOP)
      receptors, has been identified to be involved in many physiological functions
      including pain regulation. CompB (also known as J-113397) is the first non
      peptide antagonist of NOP receptors. Using the patch-clamp recording technique in
      brain slices, we have quantitatively studied the interactions of CompB with N/OFQ
      at native NOP receptors of ventrolateral neurons of the midbrain periaqueductal
      gray (PAG), a crucial region for N/OFQ-induced reversal of opioid analgesia.
      N/OFQ concentration-dependently activated inwardly rectifying K(+) channels in
      response to hyperpolarization ramps from -60 to -140 mV. CompB attenuated the
      magnitude but not the reversal potential of the K(+) current activated by N/OFQ
      in a concentration-dependent manner. The presence of CompB produced a parallel
      right-shift of the concentration-response curve to N/OFQ. The Schild plot
      analysis yielded a pA(2) value of 8.37. At concentrations up to 1 microM, CompB
      affected neither the membrane current per se nor the inwardly rectifying K(+)
      current activated by [D-Ala(2), N-Me-Phe(4),Gly-ol(5)]-enkephalin or baclofen, a
      mu-opioid and GABA(B) receptor agonist, respectively. It appears that CompB, at
      nanomolar concentrations, is a pure, selective and competitive antagonist of
      postsynaptic NOP receptors that mediate inwardly rectifying K(+) channel
      activation in ventrolateral PAG neurons.

PMID- 12069910
TI  - Epidemiology of opportunistic invasive mycoses.
AB  - Invasive aspergillosis and disseminated candidiasis are the two major
      manifestations of opportunistic invasive mycoses. Their incidence has risen
      considerably during the past decades, due to more intensive anticancer
      chemotherapy, organ transplantations, intensive care, and aggressive surgical
      interventions. Especially bone marrow transplant recipients are at risk for
      developing invasive aspergillosis. Whether the infection is acquired through
      contaminated water or through airborne spores is a matter of much debate.
      Candidemia and disseminated candidiasis commonly originate from the
      gastrointestinal tract. Abdominal surgery and mucosal damage due to anticancer
      chemotherapy are the majors factor through which gut colonization may lead to
      invasive disease. A shift in the epidemiology of disseminated candidiasis has
      been noted, with an increasing incidence of Candida glabrata, C. tropicalis and
      C. krusei strains.

PMID- 12069911
TI  - Symptoms and diagnosis of nosocomial fungal infections -- state-of-the-art.
AB  - Signs and symptoms of invasive fungal infections are seldom specific and no
      single mycological test can yield a diagnosis. Recently the Invasive Fungal
      Infections Cooperative Group (IFICG) of the European Organisation for Research
      and Treatment of Cancer and the Mycoses Study Group (MSG) of the National
      Institute of Allergy and Infectious Diseases proposed a framework consisting of 3
      elements, namely, host factors, clinical features and mycological evidence which
      should allow a diagnosis to be assigned in terms of the degree of certainty for
      patients with cancer and recipients of an HSCT. These definitions allow optimal
      use to be made of risk factors, advances in imaging techniques and new laboratory
      tests which provide indirect evidence of fungal involvement. This should make
      diagnosis more consistent and allow studies of prevention, therapy and
      epidemiology to be undertaken more efficiently.

PMID- 12069913
TI  - Management of mycoses in patients with hematologic disease and cancer -- review
      of the literature.
AB  - During the past years, progress has been made in the treatment of patients with
      cancer, and the proportion of patients achieving a complete remission and longer
      survival has increased. However, fungal infections have become one the leading
      factors contributing to morbidity and mortalitiy in patient with heamatological
      malignancies and solid tumours. Most opportunistic fungal infections are caused
      by Candida and Aspergillus species, but a growing number of less frequent fungal
      pathogens has been observed in recent years. The management of patients consist
      of a multidisciplinary approach combining radiology, new techniques in laboratory
      diagnostics such as serology and PCR as well as use of a growing armentarium of
      antifungal agents. Therapy of invasive mycosis no more rely on amphotericin B,
      but newer antifungal agents such as voriconazole and caspofungin have the
      potential to substitute the current standard therapy.

PMID- 12069912
TI  - Management of mycoses in surgical patients -- review of the literature.
AB  - Fungal infections have been recognized as major cause of morbidity and mortality
      in neutropenic and non-neutropenic surgical intensive care patients. The
      incidence of Candida has increased: it is now the fourth most often isolated
      pathogen in bloodstream infections. The incidence of Aspergillus infection in
      transplant patients is highest in heart and lung transplants: 19-26%. Most
      invasive fungal infections in surgical patients are caused by Candida spp. and
      Aspergillus spp., less by Cryptococcus spp. and may be classified as local or
      organ-related, as (chronic) disseminated, and as fungemia. There is no highly
      specific and sensitive routine test for the diagnosis of Candida and Aspergillus
      infections available; clinical signs of fungal infections are rather unspecific.
      The significance of colonization remains undetermined. In non-neutropenic
      surgical patients central venous access and broad-spectrum antibiotics are
      independent risk factors for the development of fungal infection.
      Immunsuppression, e.g., transplantation, burn injury, can render patients
      susceptible to fungal infection. This has lead to the introduction of antifungal
      prophylaxis in transplant and burned patients which has reduced the mortality for
      Candida spp. infection significantly. There is no prophylaxis available against
      Aspergillus spp. and Cryptococcus spp. Treatment of fungal infections consists of
      surgical and medical treatment for most organ-related infections. Recommendations
      for the management of fungal infections exist mostly for neutropenic patients,
      only few reports address the fungal infection of the surgical intensive care
      patient. Amphotericin B has been recommended as first line treatment for most
      severe fungal infections with fluconazole as follow-up treatment. In case of the
      development of toxic side effects of amphotericin B, mostly fluconazole or lipid
      formulations of amphotericin were favored. However, a shift in Candida strains
      towards non-albicans spp. and more resistant species was observed during recent
      years. This has lead to treatment failures in severe Candida and Aspergillus
      infections. The prognosis for invasive Aspergillus infections remains poor
      despite amphotericin B treatment. Newer azoles, e.g. voriconazole, demonstrated
      stable activity against most of these strains and may offer an option in the
      treatment of refractory fungal infections.

PMID- 12069914
TI  - Mucosal and invasive fungal infections in HIV/AIDS.
AB  - Advances in the management of fungal infections in AIDS justify this review.
      First, their incidence has fallen with the introduction of potent antiretroviral
      therapy. Now, most cases occur in patients with advanced HIV disease who have
      failed multiple antiretroviral regimens, are nonadherent to therapy, or treatment
      na ve. Immune reconstitution has reduced the incidence of these infections and
      permitted discontinuation of maintenance therapy. However, the immune response to
      antiretroviral therapy has resulted in paradoxical worsening in some cases, "so
      called immune reconstitution inflammatory syndromes". Finally, new antifungal
      agents expand our treatment choices. This review updates management of fungal
      infections in AIDS.

PMID- 12069915
TI  - Voriconazole -- better chances for patients with invasive mycoses.
AB  - The past two decades have witnessed an increase in serious fungal infections,
      without corresponding growth in available antifungal agents. Voriconazole (VRC)
      is a novel triazole antifungal, recently approved in Europe for treatment of
      serious infections caused by Aspergillus, Fusarium, Scedosporium, and resistant
      Candida species. Voriconazole has in vitro activity against yeasts and yeast-like
      fungi similar, or superior to, fluconazole (FLC), itraconazole (ITC) and
      amphotericin B (AMB). Candida albicans is generally the most susceptible yeast
      (VRC MIC subset90 of 0.06 microg/ml); C. krusei often has low MICs even in the
      face of FLU/ITC resistance. Voriconazole has demonstrated comparable, or better,
      in vitro activity than ITC and AMB against Aspergillus (mean MICs 0.19-0.58
      microg/ml), Ascomycetes, Bipolaris, Fusarium, Blastomyces dermatitidis,
      Coccidioides immitis, dermatophytes, Histoplasma capsulatum, Malassezia, and
      Scedosporium angiospermum (P. boydii). The drug possesses potent fungicidal
      activity against moulds including Aspergillus, Scedosporium, and Fusarium.
      Fungicidal activity is likely due to the high affinity of VRC for fungal 14-alpha
      demethylase, a concept supported by ultrastructural and biochemical analysis.
      Animal studies confirmed the activity of VRC against infections including
      pulmonary and invasive aspergillosis (IA); A. fumigatus endocarditis; fusariosis;
      pulmonary cryptococcosis; and invasive candidiasis. Most importantly, well
      designed human clinical trials have confirmed the efficacy of VRC in the
      treatment of candidal esophagitis, IA, and febrile neutropenia. Smaller studies
      and case reports have shown VRC is useful for salvage therapy of IA, cerebral
      aspergillosis, Scedosporium, and other fungal infections. Clinical testing has
      shown VRC is safe and well tolerated; the most common side effect is benign, self
      limited visual disturbance.

PMID- 12069916
TI  - Hydraulic redistribution of soil water by neotropical savanna trees.
AB  - The magnitude and direction of water transport by the roots of eight dominant
      Brazilian savanna (Cerrado) woody species were determined with a heat pulse
      system that allowed bidirectional measurements of sap flow. The patterns of sap
      flow observed during the dry season in species with dimorphic root systems were
      consistent with the occurrence of hydraulic redistribution of soil water, the
      movement of water from moist to drier regions of the soil profile via plant
      roots. In these species, shallow roots exhibited positive sap flow (from the soil
      into the plant) during the day and negative sap flow (from the plant into the
      soil) during the night. Sap flow in the taproots was positive throughout the 24-h
      period. Diel fluctuations in soil water potential, with maximum values occurring
      at night, provided evidence for partial rewetting of upper soil layers by water
      released from shallow roots. In other species, shallow roots exhibited negative
      sap flow during both the day and night, indicating that hydraulic redistribution
      was occurring continuously. A third sap flow pattern was observed at the end of
      the dry season after a heavy rainfall event when sap flow became negative in the
      taproot, and positive in the small roots, indicating movement of water from upper
      soil layers into shallow roots, and then into taproots and deeper soil layers.
      Experimental manipulations employed to evaluate the response of hydraulic
      redistribution to changes in plant and environmental conditions included watering
      the soil surface above shallow roots, decreasing transpiration by covering the
      plant and cutting roots where probes were inserted. Natural and manipulated
      patterns of sap flow in roots and stems were consistent with passive movement of
      water toward competing sinks in the soil and plant. Because dry shallow soil
      layers were often a stronger sink than the shoot, we suggest that the presence of
      a dimorphic root system in deciduous species may play a role in facilitating leaf
      expansion near the end of the dry season when the soil surrounding shallow
      lateral roots is still dry.

PMID- 12069918
TI  - Changes in shoot allometry with increasing tree height in a tropical canopy
      species, Elateriospermum tapos.
AB  - Allometry of shoot extension units (hereafter termed "current shoots") was
      analyzed in a Malaysian canopy species, Elateriospermum tapos Bl.
      (Euphorbiaceae). Changes in current shoot allometry with increasing tree height
      were related to growth and maintenance of tree crowns. Total biomass, biomass
      allocation ratio of non-photosynthetic to photosynthetic organs, and wood density
      of current shoots were unrelated to tree height. However, shoot structure changed
      with tree height. Compared with short trees, tall trees produced current shoots
      of the same mass but with thicker and shorter stems. Current shoots with thin and
      long stems enhanced height growth in short trees, whereas in tall trees, thick
      and short current shoots may reduce mechanical and hydraulic stresses.
      Furthermore, compared with short trees, tall trees produced current shoots with
      more leaves of lower dry mass, smaller area, and smaller specific leaf area
      (SLA). Short trees adapted to low light flux density by reducing mutual shading
      with large leaves having a large SLA. In contrast, tall trees reduced mutual
      shading within a shoot by producing more small leaves in distal than in proximal
      parts of the shoot stem. The production of a large number of small leaves
      promoted light penetration into the dense crowns of tall trees. All of these
      characteristics suggest that the change in current shoot structure with
      increasing tree height is adaptive in E. tapos, enabling short trees to maximize
      height growth and tall trees to maximize light capture.

PMID- 12069917
TI  - Water content and bark thickness of Norway spruce (Picea abies) stems: phloem
      water capacitance and xylem sap flow.
AB  - To determine the relationship between phloem transport and changes in phloem
      water content, we measured temporal and spatial variations in water content and
      sucrose, glucose and fructose concentrations in phloem samples and phloem
      exudates of 70- and 30-year-old Norway spruce trees (Picea abies (L.) Karst.).
      Large temporal and spatial variations in phloem water content (1.4-2.6 mg mg(dw)(
      1)) and phloem total sugar concentration (31-70 mg g(dw)(-1)) paralleled each
      other (r(2) = 0.83, P < 0.0001 for the temporal profile and r(2) = 0.96, P <
      0.008 for the spatial profile), indicating that phloem water content depends on
      the total amount of sugar to be transferred. Changes in phloem water content were
      unrelated to changes in bark thickness. Maximum changes in phloem water content
      calculated from dendrometer readings were only 8-11% of the maximum measured
      changes in phloem water content, indicating that reversible changes in bark
      thickness did not reflect changes in internal water relations. We also studied
      the relationship between xylem sap velocity and changes in bark thickness in 70
      year-old trees during summer 1999 and winter 1999-2000. Sap flow occurred
      sporadically throughout the winter, but there was no relationship between bark
      shrinkage or swelling and sap velocity. In winter, mean daily xylem sap velocity
      was significantly correlated with mean daily vapor pressure deficit and air
      temperature (P < 0.0001, in both cases). Changes in bark thickness corresponded
      with both short- and long-term changes in relative humidity, in both winter and
      summer. Under controlled conditions at > 0 degrees C, changes in relative
      humidity alone caused changes in thickness of boiled bark samples. Because living
      bark of Norway spruce trees contains large areas with crushed and dead sieve cell
      zones-up to 24% of the bark is air-filled space-we suggest that this space can
      compensate for volume changes in living phloem cells independently of total
      tissue water content. We conclude that changes in bark thickness are not
      indicative of changes in either phloem water capacitance or xylem sap flow.

PMID- 12069919
TI  - Leaf stomatal and epidermal cell development: identification of putative
      quantitative trait loci in relation to elevated carbon dioxide concentration in
      poplar.
AB  - Genetic variation in stomatal initiation and density, and epidermal cell size and
      number were examined in a hybrid pedigree of Populus trichocarpa T. & G. and P.
      deltoides Marsh in both ambient ([aCO2]) and elevated ([eCO2]) concentrations of
      CO2. We aimed to link anatomical traits with the underlying genetic map of F2
      Family 331, composed of 350 markers across 19 linkage groups. Leaf stomatal and
      epidermal cell traits showed pronounced differences between the original parents.
      We considered the following traits in the F2 population: stomatal density (SD),
      stomatal index (SI), epidermal cell area (ECA) and the number of epidermal cells
      per leaf (ECN). In [eCO2], adaxial SD and SI were reduced in the F2 population,
      whereas ECA increased and ECN remained unchanged. In [aCO2], four putative
      quantitative trait loci (QTL) with logarithm of the odds ratio (LOD) scores
      greater than 2.9 were found for stomatal traits on linkage group B: adaxial SI
      (LOD scores of 5.4 and 5.2); abaxial SI (LOD score of 3.3); and SD (LOD score of
      3.2). These results imply that QTL for SI and SD share linkage group B and are
      under genetic control. More moderate LOD scores (LOD scores >/= 2.5) suggest QTL
      for SI on linkage groups A and B and for SD on linkage groups B, D and X with a
      probable co-locating quantitative trait locus for SI and SD on linkage group D
      (position 46.3 cM). The QTL in both [aCO2] and [eCO2] for adaxial SD were co
      located on linkage group X (LOD scores of 3.5 and 2.6, respectively) indicating a
      similar response across both treatments. Putative QTL were located on linkage
      group A (position 89.2 cM) for both leaf size and ECN in [aCO2] and for ECA at
      almost the same position. The data provide preliminary evidence that leaf
      stomatal and cell traits are amenable to QTL analysis.

PMID- 12069920
TI  - Influence of natural temperature gradients on measurements of xylem sap flow with
      thermal dissipation probes. 1. Field observations and possible remedies.
AB  - The thermal dissipation method is simple and widely used for measuring sap flow
      in large stems. As with several other thermal methods, natural temperature
      gradients are assumed to be negligible in the sapwood being measured. We studied
      the magnitude and variability of natural temperature gradients in sapwood of
      Acacia trees growing in the Sahelian zone of Senegal, analyzed their effects on
      sap flow measurements, and investigated possible solutions. A new measurement
      approach employing cyclic heating (45 minutes of heating and 15 minutes of
      cooling; 45/15) was also tested. Three-day measurement sequences that included 1
      day without heating, a second day with continuous heating and a third day with
      cyclic heating were recorded during a 6.5-month period using probes installed at
      three azimuths in a tree trunk. Natural temperature gradients between the two
      probes of the sensor unit, spaced 8 to 10 cm vertically, were rarely negligible
      (i.e., < 0.2 degrees C): they were positive during the night and negative during
      the day, with an amplitude ranging from 0.3 to 3.5 degrees C depending on trunk
      azimuth, day and season. These temperature gradients had a direct influence on
      the signal from the continuously heated sensors, inducing fluctuations in the
      nighttime reference signal. The resulting errors in sap flow estimates can be
      greater than 100%. Correction protocols have been proposed in previous studies,
      but they were unsuitable because of the high spatial and temporal variability of
      the natural temperature gradients. We found that a measurement signal derived
      from a noncontinuous heating system could be an attractive solution because it
      appears to be independent of natural temperature gradients. The magnitude and
      variability of temperature gradients that we observed were likely exacerbated by
      the combination of open stand, high solar radiation and low sap flow rate.
      However, for all applications of the thermal dissipation method, it is wise to
      check regularly for natural temperature gradients by switching off the heater.

PMID- 12069921
TI  - Influence of natural temperature gradients on measurements of xylem sap flow with
      thermal dissipation probes. 2. Advantages and calibration of a noncontinuous
      heating system.
AB  - Natural temperature gradients in stems of trees growing in open stands give rise
      to errors when measuring sap flow by the continuous thermal dissipation method.
      Previously, we obtained evidence from field measurements that a noncontinuous
      thermal dissipation system can prevent these errors (Do and Rocheteau 2002).
      Cyclic heating (i.e., 45 minutes on and 15 minutes off; 45/15) allowed the
      derivation of an alternate signal, defined as the difference between the
      temperature signal at the end of the heating period and the temperature signal at
      the end of the cooling period. By analogy with the continuous system, we
      calculated an alternate flow index. Analysis in an artificial flow system
      confirmed that external temperature gradients have an additive effect on the
      continuous signal, whereas the alternate signal is unaffected by such gradients.
      The response of the alternate flow index to flow densities was similar for five
      combinations of heating and cooling times (45/15, 40/20, 30/30, 15/15 and 10/10
      min). The relationship was markedly different from Granier's (1985) calibration
      because measurements in cyclic systems are made under non-steady-state
      temperature conditions. We recommend the 15/15 min cycle, which allows two sap
      flow measurements per hour. We compared flow density estimates obtained from
      field measurements with the continuous and cyclic systems over 192 days with 1
      day lags between systems. Comparisons based on daily maximum values (between 0.5
      and 2.5 l dm(-2) h(-1) for the cyclic system) confirmed that differences between
      the continuous and cyclic systems, which could be greater than 100%, were linked
      to the effect of temperature gradients on the continuous system. The results
      demonstrate that, in situations where significant natural temperature gradients
      (i.e., > 0.2 degrees C) are likely, the cyclic system improves the accuracy of
      sap flow measurements made with thermal dissipation probes.

PMID- 12069922
TI  - Physical analysis of the process of cavitation in xylem sap.
AB  - Recent studies have confirmed that cavitation in xylem is caused by air bubbles.
      We analyzed expansion of a preexistent bubble adhering to a crack in a conduit
      wall and a bubble formed by the passage of air through a pore of a pit membrane,
      a process known as air seeding. We consider that there are two equilibrium states
      for a very small air bubble in the xylem: one is temporarily stable with a bubble
      radius r1 at point s1 on the curve P(r) relating pressure within the bubble (P)
      with bubble radius (r); the other is unstable with a bubble radius r2 at point s2
      on Pr (where r1 < r2). In each equilibrium state, the bubble collapse pressure
      (2sigma/r, where sigma is surface tension of water) is balanced by the pressure
      difference across its surface. In the case of a bubble from a crack in a conduit
      wall, which is initially at point s1, expansion will occur steadily as water
      potential decreases. The bubble will burst only if the xylem pressure drops below
      a threshold value. A formula giving the threshold pressure for bubble bursting is
      proposed. In the case of an air seed entering a xylem conduit through a pore in a
      pit membrane, its initial radius may be r2 (i.e., the radius of the pore by which
      the air seed entered the vessel) at point s2 on Pr. Because the bubble is in an
      unstable equilibrium when entering the conduit, it can either expand or contract
      to point s1. As water vaporizes into the air bubble at s2, P rises until it
      exceeds the gas pressure that keeps the bubble in equilibrium, at which point the
      bubble will burst and induce a cavitation event in accordance with the air
      seeding hypothesis. However, other possible perturbations could make the air
      seeded bubble contract to s1, in which case the bubble will burst at a threshold
      pressure proposed for a bubble expanding from a crack in a conduit wall. For this
      reason some cavitation events may take place at a xylem threshold pressure (Pl'*)
      other than that determined by the formula, Plp'* = -2sigma/rp, proposed by Sperry
      and Tyree (1988), which is applicable only to air-seeded bubbles at s2. The more
      general formula we propose for calculating the threshold pressure for bubble
      breaking is consistent with the results of published experiments.

PMID- 12069923
TI  - Neutral lipids and phospholipids in Scots pine (Pinus sylvestris) sapwood and
      heartwood.
AB  - Variations in the concentration and composition of triacylglycerols, free fatty
      acids and phospholipids were analyzed in Scots pine (Pinus sylvestris L.) trees
      at five sites. Disks were taken at breast height or at a height of 4 m from the
      stems of 81 trees differing in diameter and growth rate. The mean concentration
      of triacylglycerols in sapwood was 26 mg g(-1) dry mass; however, variation among
      trees was large (16-51 mg g(dm)(-1)). The concentration of triacylglycerols was
      slightly larger at 4 m height in the stem than at breast height. Concentrations
      of triacylglycerols did not differ between the sapwood of young and small
      diameter stems (DBH < 12 cm) and the sapwood of old stems (DBH > 36 cm).
      Concentrations of free fatty acids were negligible in the outer sapwood, but
      ranged between 5 and 18 mg g(dm)(-1) in the heartwood. The most abundant fatty
      acids of triacylglycerols were oleic (18:1), linoleic (18:2omega6, 18:2Delta5,9),
      linolenic (pinolenic, 18:3Delta5,9,12 and 18:3omega3) and eicosatrienoic acid
      (20:3Delta5,11,14 and 20:3omega6). The concentration of linoleic acid comprised
      39-46% of the triacylglycerol fatty acids and the concentration was higher in the
      slow-growing stem from northern Finland than in the stems from southern Finland.
      Major phospholipids were detected only in sapwood, and only traces of lipid
      phosphorus were detected in heartwood.

PMID- 12069924
TI  - Growth and reproductive characteristics of the columnar cactus Stenocereus
      queretaroensis and their relationships with environmental factors and
      colonization by arbuscular mycorrhizae.
AB  - Three natural populations of pitayo (Stenocereus queretaroensis (Weber) Buxbaum),
      a columnar arborescent cactus, were studied in their subtropical environments in
      western Mexico. All of the sites were characterized by shallow, nutrient-poor
      soils. Percentage of colonization by arbuscular mycorrhizae (AM) fungi, stem
      growth, fruit mass, and percentage germination were greater in S. queretaroensis
      at Autlan, Jalisco (AJ) than at Zacoalco de Torres, Jalisco (ZTJ) or Santa Rosa,
      Zacatecas (SRZ). The onset of root colonization by arbuscular mycorrhizae during
      the middle of the summer wet period preceded increases in stem extension rate and
      stem phosphorus concentration. Based on previous studies of effects of
      environmental factors on photosynthesis, climatic conditions were more favorable
      for photosynthesis at AJ than at SRZ and ZTJ, as indicated by the amount of
      summer rainfall, the amount of light, and the moderate air temperatures that
      prevailed during the fall and winter seasons. There was a significant positive
      correlation between stem growth and percentage of total root length colonized by
      arbuscules of AM fungi for S. queretaroensis at SRZ and AJ, but not at ZTJ. A
      negative significant correlation was observed between stem growth and maximal and
      minimal air temperatures at the three study sites. Stem growth was positively
      related to rainfall only at SRZ, and light was statistically related to stem
      growth only at ZTJ. Among sites, S. queretaroensis at AJ had the highest carbon
      gain and greatest AM colonization, creating physiological conditions that led to
      the highest stem growth, fruit mass and percentage of seed germination.

PMID- 12069925
TI  - Ethical policies and procedures.

PMID- 12069926
TI  - Exercise.

PMID- 12069927
TI  - Chemokines and chemokine receptors in leukocyte trafficking.
AB  - Chemokines regulate inflammation, leukocyte trafficking, and immune cell
      differentiation. The role of chemokines in homing of naive T lymphocytes to
      secondary lymphatic organs is probably the best understood of these processes,
      and information on chemokines in inflammation, asthma, and neurological diseases
      is rapidly increasing. Over the past 15 years, understanding of the size and
      functional complexity of the chemokine family of peptide chemoattractants has
      grown substantially. In this review, we first present information regarding the
      structure, expression, and signaling properties of chemokines and their
      receptors. The second part is a systems physiology-based overview of the roles
      that chemokines play in tissue-specific homing of lymphocyte subsets and in
      trafficking of inflammatory cells. This review draws on recent experimental
      findings as well as current models proposed by experts in the chemokine field.

PMID- 12069928
TI  - Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from
      animal models.
AB  - Normal pregnancy is associated with reductions in total vascular resistance and
      arterial pressure possibly due to enhanced endothelium-dependent vascular
      relaxation and decreased vascular reactivity to vasoconstrictor agonists. These
      beneficial hemodynamic and vascular changes do not occur in women who develop
      preeclampsia; instead, severe increases in vascular resistance and arterial
      pressure are observed. Although preeclampsia represents a major cause of maternal
      and fetal morbidity and mortality, the vascular and cellular mechanisms
      underlying this disorder have not been clearly identified. Studies in
      hypertensive pregnant women and experimental animal models suggested that
      reduction in uteroplacental perfusion pressure and the ensuing placental
      ischemia/hypoxia during late pregnancy may trigger the release of placental
      factors that initiate a cascade of cellular and molecular events leading to
      endothelial and vascular smooth muscle cell dysfunction and thereby increased
      vascular resistance and arterial pressure. The reduction in uterine perfusion
      pressure and the ensuing placental ischemia are possibly caused by inadequate
      cytotrophoblast invasion of the uterine spiral arteries. Placental ischemia may
      promote the release of a variety of biologically active factors, including
      cytokines such as tumor necrosis factor-alpha and reactive oxygen species.
      Threshold increases in the plasma levels of placental factors may lead to
      endothelial cell dysfunction, alterations in the release of vasodilator
      substances such as nitric oxide (NO), prostacyclin (PGI(2)), and endothelium
      derived hyperpolarizing factor, and thereby reductions of the NO-cGMP, PGI(2)
      cAMP, and hyperpolarizing factor vascular relaxation pathways. The placental
      factors may also increase the release of or the vascular reactivity to
      endothelium-derived contracting factors such as endothelin, thromboxane, and ANG
      II. These contracting factors could increase intracellular Ca(2+) concentrations
      ([Ca(2+)](i)) and stimulate Ca(2+)-dependent contraction pathways in vascular
      smooth muscle. The contracting factors could also increase the activity of
      vascular protein kinases such as protein kinase C, leading to increased
      myofilament force sensitivity to [Ca(2+)](i) and enhancement of smooth muscle
      contraction. The decreased endothelium-dependent mechanisms of vascular
      relaxation and the enhanced mechanisms of vascular smooth muscle contraction
      represent plausible causes of the increased vascular resistance and arterial
      pressure associated with preeclampsia.

PMID- 12069930
TI  - Sleep deprivation decreases glycogen in the cerebellum but not in the cortex of
      young rats.
AB  - We tested whether brain glycogen reserves were depleted by sleep deprivation (SD)
      in Long-Evans rats 20-59 days old. Animals were sleep deprived beginning at
      lights on and then immediately killed by microwave irradiation. Glycogen and
      glucose levels were measured by a fluorescence enzymatic assay. In all age
      groups, SD reduced cerebellar glycogen levels by an average of 26% after 6 h of
      SD. No changes were observed in the cortex after 6 h of SD, but in the oldest
      animals, 12 h of SD increased cortical glycogen levels. There was a developmental
      increase in basal glycogen levels in both the cortex and cerebellum that peaked
      at 34 days and declined thereafter. Robust differences in cortical and cerebellar
      glycogen levels in response to enforced waking may reflect regional differences
      in energy utilization and regulation during wakefulness. These results show that
      brain glycogen reserves are sensitive to SD.

PMID- 12069929
TI  - Principles for interpreting interactions among the multiple systems that
      influence food intake.
AB  - The widespread use of molecular biological tools has led to a pronounced increase
      in the number of signals that are now implicated in the controls of food intake
      and body weight. However, a complete understanding of the roles of these multiple
      signals requires that we assess how they interact with one another to alter
      ingestive behavior. Although many such experiments are being conducted, the
      methods employed to delineate these interactions are often fraught with
      interpretive difficulties. The purpose of this article is to explore these
      difficulties and offer practical advice for minimizing these issues in
      experiments that seek to explore the important interactions among these signals.
      In particular, the issues of additive vs. nonadditive results, the use of sub- or
      suprathreshold dose combinations, and the choosing of multiple-dose analyses are
      all addressed. Furthermore, the possibilities of using intake measures other than
      cumulative intake and complementary nonbehavioral endpoints are encouraged.

PMID- 12069931
TI  - Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions
      of angiotensin II.
AB  - The present study examined the effects of ANG II on the renal synthesis of 20
      hydroxyeicosatetraenoic acid (20-HETE) and its contribution to the renal
      vasoconstrictor and the acute and chronic pressor effects of ANG II in rats. ANG
      II (10(-11) to 10(-7) mol/l) reduced the diameter of renal interlobular arteries
      treated with inhibitors of nitric oxide synthase and cyclooxygenase,
      lipoxygenase, and epoxygenase by 81 +/- 8%. Subsequent blockade of the synthesis
      of 20-HETE with 17-octadecynoic acid (1 micromol/l) increased the ED(50) for ANG
      II-induced constriction by a factor of 15 and diminished the maximal response by
      61%. Graded intravenous infusion of ANG II (5-200 ng/min) dose dependently
      increased mean arterial pressure (MAP) in thiobutylbarbitol-anesthetized rats by
      35 mmHg. Acute blockade of the formation of 20-HETE with dibromododecenyl
      methylsulfimide (DDMS; 10 mg/kg) attenuated the pressor response to ANG II by
      40%. An intravenous infusion of ANG II (50 ng. kg(-1). min(-1)) in rats for 5
      days increased the formation of 20-HETE and epoxyeicosatrienoic acids (EETs) in
      renal cortical microsomes by 60 and 400%, respectively, and increased MAP by 78
      mmHg. Chronic blockade of the synthesis of 20-HETE with intravenous infusion of
      DDMS (1 mg. kg(-1). h(-1)) or EETs and 20-HETE with 1-aminobenzotriazole (ABT;
      2.2 mg. kg(-1). h(-1)) attenuated the ANG II-induced rise in MAP by 40%. Control
      urinary excretion of 20-HETE averaged 350 +/- 23 ng/day and increased to 1,020 +/
      105 ng/day in rats infused with ANG II (50 ng. kg(-1). min(-1)) for 5 days. In
      contrast, urinary excretion of 20-HETE only rose to 400 +/- 40 and 600 +/- 25
      ng/day in rats chronically treated with ANG II and ABT or DDMS respectively.
      These results suggest that acute and chronic elevations in circulating ANG II
      levels increase the formation of 20-HETE in the kidney and peripheral vasculature
      and that 20-HETE contributes to the acute and chronic pressor effects of ANG II.

PMID- 12069932
TI  - Waterborne vs. dietary copper uptake in rainbow trout and the effects of previous
      waterborne copper exposure.
AB  - Juvenile rainbow trout (Oncorhynchus mykiss) were exposed to waterborne Cu (22
      microg/l) in moderately hard water for up to 28 days. Relative to control fish
      kept at background Cu levels (2 microg/l), Cu-preexposed fish displayed decreased
      uptake rates of waterborne Cu via the gills but not of dietary Cu via the gut
      during 48-h exposures to (64)Cu-radiolabeled water and diet, respectively. At
      normal dietary and waterborne Cu levels, the uptake rates of dietary Cu into the
      whole body without the gut were 0.40-0.90 ng. g(-1). h(-1), >10-fold higher than
      uptake rates of waterborne Cu into the whole body without the gills, which were
      0.02-0.07 ng. g(-1). h(-1). Previously Cu-exposed fish showed decreased new Cu
      accumulation in the gills, liver, and carcass during waterborne (64)Cu exposures
      and in the liver during dietary (64)Cu exposures. A 3-h gill Cu-binding assay
      showed downregulation of the putative high-affinity, low-capacity Cu transporters
      and upregulation of the low-affinity, high-capacity Cu transporters at the gills
      in Cu-preexposed fish. Exchangeable Cu pools in all the tissues were higher
      during dietary than during waterborne (64)Cu exposures, and previous Cu exposure
      reduced waterborne exchangeable Cu pools in gill, liver, and carcass. Overall,
      these results suggest a quantitatively greater role for the dietary than for the
      waterborne route of Cu uptake, a key role for the gill in Cu homeostasis, and
      important roles for the liver and gut in the normal metabolism of Cu in fish.

PMID- 12069933
TI  - 48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth
      muscle cell hyperpolarization.
AB  - Chronic hypoxia (CH) results in reduced sensitivity to vasoconstrictors in
      conscious rats that persists upon restoration of normoxia. We hypothesized that
      this effect is due to endothelium-dependent hyperpolarization of vascular smooth
      muscle (VSM) cells after CH. VSM cell resting membrane potential was determined
      for superior mesenteric artery strips isolated from CH rats (PB = 380 Torr for 48
      h) and normoxic controls. VSM cells from CH rats studied under normoxia were
      hyperpolarized compared with controls. Resting vessel wall intracellular Ca(2+)
      concentration ([Ca(2+)](i)) and pressure-induced vasoconstriction were reduced in
      vessels isolated from CH rats compared with controls. Vasoconstriction and
      increases in vessel wall [Ca(2+)](i) in response to the alpha(1)-adrenergic
      agonist phenylephrine (PE) were also blunted in resistance arteries from CH rats.
      Removal of the endothelium normalized resting membrane potential, resting vessel
      wall [Ca(2+)](i), pressure-induced vasoconstrictor responses, and PE-induced
      constrictor and Ca(2+) responses between groups. Whereas VSM cell
      hyperpolarization persisted in the presence of nitric oxide synthase inhibition,
      heme oxygenase inhibition restored VSM cell resting membrane potential in vessels
      from CH rats to control levels. We conclude that endothelial derived CO accounts
      for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity
      after CH.

PMID- 12069934
TI  - Synergistic interactions between airway afferent nerve subtypes mediating reflex
      bronchospasm in guinea pigs.
AB  - The hypothesis that airway afferent nerve subtypes act synergistically to
      initiate reflex bronchospasm in guinea pigs was addressed. Laryngeal mucosal
      application of capsaicin or bradykinin or the epithelial lipoxygenase metabolite
      15(S)-hydroxyeicosatetraenoic acid evoked slowly developing but pronounced and
      sustained increases in tracheal cholinergic tone in situ. These reflexes were
      reversed by atropine and prevented by vagotomy, trimethaphan, or laryngeal
      denervation. Central nervous system-acting neurokinin receptor antagonists also
      abolished the reflexes without altering baseline cholinergic tone. Baseline tone
      was, however, reversed by disrupting pulmonary afferent innervation while
      preserving the innervation of the trachea and larynx. Surprisingly, selective
      pulmonary denervation also prevented the laryngeal capsaicin-induced tracheal
      reflexes, suggesting that laryngeal C-fibers act synergistically with
      continuously active intrapulmonary mechanoreceptors to initiate reflex
      bronchospasm. Indeed, reflex bronchospasm evoked by histamine was markedly
      potentiated by bradykinin, an effect mimicked by intracerebroventricular, but not
      intravenous, substance P. These data, as well as anatomic evidence for afferent
      nerve subtype convergence in the commissural nucleus of the solitary tract,
      suggest that airway nociceptors and mechanoreceptors may act synergistically to
      regulate airway tone.

PMID- 12069935
TI  - GLP-1 receptor signaling contributes to anorexigenic effect of centrally
      administered oxytocin in rats.
AB  - The present study examined possible interactions between central glucagon-like
      peptide-1 (GLP-1) and oxytocin (OT) neural systems by determining whether
      blockade of GLP-1 receptors attenuates OT-induced anorexia and vice versa. Male
      rats were acclimated to daily 4-h food access. In the first experiment, rats were
      infused centrally with GLP-1 receptor antagonist or vehicle, followed by an
      anorexigenic dose of synthetic OT. Access to food began 20 min later. Cumulative
      food intake was measured every 30 min for 4 h. In the second experiment, rats
      were infused with OT receptor blocker or vehicle, followed by synthetic GLP-1 [(7
      36) amide]. Subsequent food intake was monitored as before. The anorexigenic
      effect of OT was eliminated in rats pretreated with the GLP-1 receptor
      antagonist. Conversely, GLP-1-induced anorexia was not affected by blockade of OT
      receptors. In a separate immunocytochemical study, OT-positive terminals were
      found closely apposed to GLP-1-positive perikarya, and central infusion of OT
      activated c-Fos expression in GLP-1 neurons. These findings implicate endogenous
      GLP-1 receptor signaling as an important downstream mediator of anorexia in rats
      after activation of central OT neural pathways.

PMID- 12069936
TI  - ANG II stimulation of neuritogenesis involves protein kinase B in brain neurons.
AB  - Stimulation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)
      signal transduction pathway has been linked to the neuromodulatory action of ANG
      II in the brain neurons of the spontaneously hypertensive rat (Yang H and Raizada
      MK. J Neurosci 19: 2413-2423, 1999). The cellular consequences of this signaling
      pathway, however, remain unknown in the brain neurons from the normotensive rat.
      The present study was designed to test the hypothesis that the PI3K-PKB signaling
      cascade activates an ANG II-mediated neuritogenic action by stimulating cellular
      growth-associated protein-43 (GAP-43) and neurite extension in Wistar-Kyoto rat
      brain neurons. ANG II activation of the ANG II type 1 receptor caused increases
      in PKB activity, cellular GAP-43 levels, and neurite extension in a time- and
      dose-dependent manner. Depletion of PKB by specific antisense oligonucleotides
      attenuated ANG II stimulation of both GAP-43 and neurite extension. PKB
      involvement in neuritogenic action is further supported by the observation that
      neurons that overexpress PKB develop extensive neuronal processes in the absence
      of ANG II. These observations demonstrate that PKB is directly involved in ANG II
      mediated effects and may recruit both nuclear and cytoplasmic signaling systems
      for this action.

PMID- 12069937
TI  - Dual actions of caffeine on voltage-dependent currents and intracellular calcium
      in taste receptor cells.
AB  - Although the numerous stimuli representing the taste quality of bitterness are
      known to be transduced through multiple mechanisms, recent studies have suggested
      an unpredicted complexity of the transduction pathways for individual bitter
      stimuli. To investigate this notion more thoroughly, a single prototypic bitter
      stimulus, caffeine, was studied by using patch-clamp and ratiometric imaging
      techniques on dissociated rat taste receptor cells. At behaviorally relevant
      concentrations, caffeine produced strong inhibition of outwardly and inwardly
      rectifying potassium currents. Caffeine additionally inhibited calcium current,
      produced a weaker inhibition of sodium current, and was without effect on
      chloride current. Consistent with its effects on voltage-dependent currents,
      caffeine caused a broadening of the action potential and an increase of the input
      resistance. Caffeine was an effective stimulus for elevation of intracellular
      calcium. This elevation was concentration dependent, independent of extracellular
      calcium or ryanodine, and dependent on intracellular stores as evidenced by
      thapsigargin treatment. These dual actions on voltage-activated ionic currents
      and intracellular calcium levels suggest that a single taste stimulus, caffeine,
      utilizes multiple transduction mechanisms.

PMID- 12069938
TI  - TNF-alpha enhances contraction and inhibits endothelial NO-cGMP relaxation in
      systemic vessels of pregnant rats.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is elevated in the plasma of preeclamptic
      women and may have a role in pregnancy-induced hypertension. However, whether the
      hemodynamic effects of TNF-alpha reflect the direct effects on vascular
      reactivity is unclear. We tested the hypothesis that TNF-alpha impairs
      endothelium-dependent relaxation and enhances vascular contraction in systemic
      vessels of pregnant rats. We measured isometric contraction in aortic strips
      isolated from virgin and pregnant Sprague-Dawley rats (nontreated vs. treated for
      2 h with 10-1,000 pg/ml TNF-alpha). In endothelium-intact vascular strips, TNF
      alpha caused greater enhancement of phenylephrine (Phe) contraction in pregnant
      than virgin rats. TNF-alpha caused significant inhibition of ACh- and bradykinin
      induced vascular relaxation and nitrite/nitrate production that were more
      prominent in pregnant than virgin rats. N(G)-nitro-L-arginine methyl ester [L
      NAME, 100 microM, an inhibitor of nitric oxide (NO) synthase] or 1H
      [1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 1 microM, an inhibitor of cGMP
      production in smooth muscle) inhibited ACh relaxation and enhanced Phe
      contraction in nontreated but to a lesser extent in TNF-alpha-treated vessels,
      particularly those of pregnant rats. Endothelium removal enhanced Phe contraction
      in nontreated but not TNF-alpha-treated vessels, especially those of pregnant
      rats. Relaxation of Phe contraction with the NO donor sodium nitroprusside was
      not different between nontreated and TNF-alpha-treated vessels. Thus TNF-alpha
      enhances vascular contraction and inhibits endothelium-dependent NO-cGMP-mediated
      vascular relaxation in systemic vessels, particularly those of pregnant rats. The
      results support a direct role for TNF-alpha as a possible mediator of increased
      vascular resistance associated with pregnancy-induced hypertension.

PMID- 12069939
TI  - Blockade of fatty acid oxidation mimics phase II-phase III transition in a
      fasting bird, the king penguin.
AB  - This study tests the hypothesis that the metabolic and endocrine shift
      characterizing the phase II-phase III transition during prolonged fasting is
      related to a decrease in fatty acid (FA) oxidation. Changes in plasma
      concentrations of various metabolites and hormones and in lipolytic fluxes, as
      determined by continuous infusion of [2-(3)H]glycerol and [1-(14)C]palmitate,
      were examined in vivo in spontaneously fasting king penguins in the phase II
      status (large fat stores, protein sparing) before, during, and after treatment
      with mercaptoacetate (MA), an inhibitor of FA oxidation. MA induced a 7-fold
      decrease in plasma beta-hydroxybutyrate and a 2- to 2.5-fold increase in plasma
      nonesterified fatty acids (NEFA), glycerol, and triacylglycerols. MA also
      stimulated lipolytic fluxes, increasing the rate of appearance of NEFA and
      glycerol by 60-90%. This stimulation might be partly mediated by a doubling of
      circulating glucagon, with plasma insulin remaining unchanged. Plasma glucose
      level was unaffected by MA treatment. Plasma uric acid increased 4-fold,
      indicating a marked acceleration of body protein breakdown, possibly mediated by
      a 2.5-fold increase in circulating corticosterone. Strong similarities between
      these changes and those observed at the phase II-phase III transition in fasting
      penguins support the view that entrance into phase III, and especially the end of
      protein sparing, is related to decreased FA oxidation, rather than reduced NEFA
      availability. MA could be therefore a useful tool for understanding mechanisms
      underlying the phase II-phase III transition in spontaneously fasting birds and
      the associated stimulation of feeding behavior.

PMID- 12069940
TI  - Decreased susceptibility of cardiac function to hypoxia-reoxygenation in renin
      angiotensinogen transgenic rats.
AB  - We tested the hypothesis that the renin-angiotensin system (RAS) protects the
      contractile function of the myocardium against the damaging effect of hypoxia
      reoxygenation. For this purpose, the contractility of isolated papillary muscles
      from wild-type (WT) rats and from rats expressing human renin and angiotensinogen
      as transgenes (TGR) was compared. After 15 min of hypoxia, peak force (PF) was
      decreased to 24 +/- 5% of the normoxic values in TGR (n = 10) and to 18 +/- 1% in
      WT rats (n = 12). PF and relaxation rates recovered completely in TGR but not in
      WT rats during 45 min of reoxygenation. Improved contractility of the papillary
      muscles from TGR during hypoxia-reoxygenation correlated with increased
      glutathione peroxidase activities and creatine kinase (CK)-MB and CK-BB isoenzyme
      levels. On the other hand, inhibition of the RAS with ramipril (1 mg/kg body wt
      for 3 wk) in WT animals resulted in deterioration of the contractile function of
      the papillary muscles during reoxygenation compared with untreated rats. These
      findings suggest that activation of the RAS protects contractile function of the
      cardiac muscle against hypoxia-reoxygenation, possibly through changes in CK
      isoenzymes and enhanced antioxidant capacity.

PMID- 12069941
TI  - Opioid receptor blockade in rat nucleus tractus solitarius alters amygdala
      dynorphin gene expression.
AB  - It has been suggested that an opioidergic feeding pathway exists between the
      nucleus of the solitary tract (NTS) and the central nucleus of the amygdala. We
      studied the following three groups of rats: 1) artificial cerebrospinal fluid
      (CSF) infused in the NTS, 2) naltrexone (100 microg/day) infused for 13 days in
      the NTS, and 3) artificial CSF infused in the NTS of rats pair fed to the
      naltrexone-infused group. Naltrexone administration resulted in a decrease in
      body weight and food intake. Also, naltrexone infusion increased dynorphin, but
      not enkephalin, gene expression in the amygdala, independent of the naltrexone
      induced reduction in food intake. Gene expression of neuropeptide Y in the
      arcuate nucleus and neuropeptide Y peptide levels in the paraventricular nucleus
      did not change because of naltrexone infusion. However, naltrexone induced an
      increase in serum leptin compared with pair-fed controls. Thus chronic
      administration of naltrexone in the NTS increased dynorphin gene expression in
      the amygdala, further supporting an opioidergic feeding pathway between these two
      brain sites.

PMID- 12069942
TI  - Cardiac adenosine production in rat genetic models of low and high exercise
      capacity.
AB  - We previously demonstrated that Copenhagen (COP) and DA inbred rat strains show a
      wide difference in a test for aerobic treadmill running that correlated
      positively with isolated cardiac function. The purpose of this study was to test
      adenosine production as a candidate intermediate phenotype that may explain part
      of the difference in running and cardiac performance in these genetic models for
      low and high aerobic capacity. Adenosine production was measured as the activity
      of soluble 5'-nucleotidase and membrane-bound ecto-5'-nucleotidase in the
      membrane pellet and supernatant fractions of left and right ventricular muscle
      and gracilis muscle taken from 10 DA and 10 COP rats. Ecto-5'-nucleotidase
      activity in the membrane pellet of hearts from both DA and COP accounted for the
      vast majority of the total tissue adenosine production (>90% in the left
      ventricle and >80% in the right ventricle). Ecto-5'-nucleotidase activity in the
      pellet fraction was significantly higher in the left (22.4%) and right (46.1%)
      ventricles of DA rats compared with COP rats, with no differences in total
      protein content. There were no significant differences between the strains for 5'
      nucleotidase activity in the cardiac supernatant, the gracilis pellet, or the
      gracilis supernatant. These data support the hypothesis that an increase in
      cardiac adenosine production may contribute to the greater aerobic running
      capacity of the DA rats.

PMID- 12069943
TI  - Effects of supine, prone, and lateral positions on cardiovascular and renal
      variables in humans.
AB  - The hypothesis was tested that changing the direction of the transverse
      gravitational stress in horizontal humans modulates cardiovascular and renal
      variables. On different study days, 14 healthy males were placed for 6 h in
      either the horizontal supine or prone position following 3 h of being supine.
      Eight of the subjects were in addition investigated in the horizontal left
      lateral position. Compared with supine, the prone position slightly increased
      free water clearance (349 +/- 38 vs. 447 +/- 39 ml/6 h, P = 0.05) and urine
      output (1,387 +/- 55 vs. 1,533 +/- 52 ml/6 h, P = 0.06) with no statistically
      significant effect on renal sodium excretion (69 +/- 3 vs. 76 +/- 5 mmol/6 h, P =
      0.21). Mean arterial pressure and left atrial diameter were similar comparing
      effects of supine with prone. The prone position induced an increase in heart
      rate (54 +/- 2 to 58 +/- 2 beats/min, P < 0.05), total peripheral vascular
      resistance (13 +/- 1 to 16 +/- 1 mmHg. min(-1). l(-1), P < 0.05), forearm venous
      plasma concentration of norepinephrine (97 +/- 9 to 123 +/- 16 pg/ml, P < 0.05),
      and atrial natriuretic peptide (49 +/- 4 to 79 +/- 12 pg/ml, P < 0.05), whereas
      stroke volume decreased (122 +/- 5 to 102 +/- 3 ml, P < 0.05, n = 6). The left
      lateral position had no effect on renal variables, whereas left atrial diameter
      increased (32 +/- 1 to 35 +/- 1 mm, P < 0.05) and mean arterial pressure
      decreased (90 +/- 2 to mean value of 85 +/- 2 mmHg, P < 0.05). In conclusion, the
      prone position reduced stroke volume and increased sympathetic nervous activity,
      possibly because of mechanical compression of the thorax with slight impediment
      of arterial filling. The mechanisms of the slightly augmented urine output in
      prone position require further experimentation.

PMID- 12069944
TI  - The respiratory metabolism of a lizard (Lacerta vivipara) in supercooled and
      frozen states.
AB  - We investigated the respiratory metabolism of the overwintering lizard Lacerta
      vivipara while in either supercooled or frozen states. With a variable pressure
      and volume microrespirometer and a chromatograph, we show that the oxygen
      consumption of the supercooled animals showed a nonlinear relationship with
      temperature and an aerobic metabolism demand between 0.5 and -1.5 degrees C. A
      significant increase in the respiratory quotient (RQ) values indicated an
      increasing contribution by the anaerobic pathways with decreasing temperature. In
      the frozen state, two phases are easily detectable and are probably linked to the
      ice formation within the body. During the first 5-6 h, the animals showed an
      oxygen consumption of 3.52 +/- 0.28 microl. g(-1). h(-1) and a RQ value of 0.52
      +/- 0.09. In contrast, after ice equilibrium, oxygen consumption decreased
      sharply (0.55 +/- 0.09 microl. g(-1). h(-1)) and the RQ values increased (2.49 +/
      0.65). The present study confirms the fact that supercooled invertebrates and
      vertebrates respond differently to subzero temperatures, in terms of aerobic
      metabolism, and it shows that aerobic metabolism persists under freezing
      conditions.

PMID- 12069946
TI  - In vivo downregulation of protein synthesis in the snail Helix apersa during
      estivation.
AB  - Protein synthesis is downregulated during metabolic depression in a number of
      systems where the metabolic depression is effected by obvious extrinsic cues. The
      metabolic depression of the estivating land snail Helix apersa occurs in the
      absence of any obvious physiological stress and has an intrinsic component
      independent of temperature, pH, O(2) status, or osmolality. We show that this
      metabolic depression is accompanied by a downregulation of protein synthesis in
      vivo. The rate of protein synthesis decreases in two major tissues during
      estivation: to 23% and 53% of the awake rate in hepatopancreas and foot muscle,
      respectively. We show from calculations of the theoretical contribution of
      protein synthesis to total O(2) consumption that the depression of protein
      synthesis must be a significant, obligate, in vivo component of metabolic
      depression in H. aspersa.

PMID- 12069945
TI  - Angiotensin II attenuates the natriuresis of water immersion in humans.
AB  - The hypothesis was tested that suppression of generation of ANG II is one of the
      mechanisms of the water immersion (WI)-induced natriuresis in humans. In one
      protocol, eight healthy young males were subjected to 3 h of 1) WI (WI +
      placebo), 2) WI combined with ANG II infusion of 0.5 ng. kg(-1). min(-1) (WI +
      ANG II-low), and 3) a seated time control (Con). In another almost identical
      protocol, 7-10 healthy young males were investigated to delineate the tubular
      site(s) of action of ANG II by the lithium clearance method (C(Li)) and were on
      an additional fourth study day subjected to infusion of ANG II at a rate of 1.5
      ng. kg(-1). min(-1) (WI + ANG II-high). During WI + placebo, plasma concentration
      of ANG II decreased from 16 +/- 2 to 8 +/- 1 pg/ml (P < 0.05) and renal sodium
      excretion increased from 104 +/- 15 to 294 +/- 27 micromol/min (P < 0.05). During
      WI + ANG II-low, plasma ANG II was not suppressed by WI, and the natriuresis was
      blunted by 52 +/- 13% (P < 0.05). During WI + ANG II-low and WI + ANG II-high, an
      increase in C(Li) was prevented that was otherwise observed during WI, and
      fractional distal reabsorption of sodium was facilitated. In conclusion,
      maintaining plasma concentration of ANG II unchanged at the level of control
      attenuates the natriuresis of WI considerably in humans. Therefore, suppression
      of generation of ANG II is an important mechanism of the natriuresis of WI in
      humans. Furthermore, infusion of ANG II during WI prevents an otherwise induced
      increase in C(Li) and facilitates the fractional distal reabsorption of sodium,
      probably via an effect on aldosterone release.

PMID- 12069947
TI  - Are developing beta-adrenoceptors able to desensitize? Acute and chronic effects
      of beta-agonists in neonatal heart and liver.
AB  - During fetal and neonatal development, beta-adrenergic receptors (beta-ARs)
      appear to be resistant to desensitization by beta-agonist drugs. To determine the
      mechanisms underlying the regulatory differences between adults and neonates, we
      administered isoproterenol, a mixed beta(1)/beta(2)-AR agonist, and terbutaline,
      a beta(2)-selective agonist. Effects were examined in the ensuing 4 h after a
      single injection, or after the last of four daily injections. We prepared cell
      membranes from heart (predominantly beta(1)-ARs) and liver (predominantly beta(2)
      ARs) and assessed signal transduction in the adenylyl cyclase (AC) pathway. In
      the first few hours after a single administration of isoproterenol to adult rats,
      cardiac beta-ARs showed activation of G proteins (elevated AC response to
      forskolin) and desensitization of beta-AR-mediated responses; after the fourth
      injection, heterologous desensitization emerged, characterized by a loss of
      signaling mediated either through beta-ARs or glucagon receptors. Terbutaline
      evoked an increase in the forskolin response but no desensitization of receptor
      mediated responses. When we gave the same treatments to neonatal rats, we
      observed cardiac G protein activation, but there was neither homologous nor
      heterologous desensitization of beta-ARs or glucagon receptors. In the adult
      liver, isoproterenol and terbutaline both failed to evoke desensitization,
      regardless of whether the drugs were given once or for 4 days. In neonates,
      however, acute or chronic treatment elicited homologous desensitization of beta
      AR-mediated AC signaling, while sensitizing the response to glucagon. These
      results show that neonatal beta-ARs are inherently capable of desensitization in
      some, but not all, cell types; cellular responses can be maintained through
      heterologous sensitization of signaling proteins downstream from the receptor.
      Differences from adult patterns of response are highly tissue selective and are
      likely to depend on ontogenetic differences in subtypes of beta-ARs and AC.

PMID- 12069948
TI  - Role of alpha(2)-macroglobulin in fever and cytokine responses induced by
      lipopolysaccharide in mice.
AB  - Alpha(2)-macroglobulin (alpha(2)M) is not only a proteinase inhibitor in mammals,
      but it is also a specific cytokine carrier that binds pro- and anti-inflammatory
      cytokines implicated in fever, including interleukin (IL)-1beta, IL-6, and tumor
      necrosis factor-alpha (TNF-alpha). To define the role of alpha(2)M in regulation
      of febrile and cytokine responses, wild-type mice and mice deficient in alpha(2)M
      (alpha(2)M -/-) were injected with lipopolysaccharide (LPS). Changes in body
      temperature as well as plasma levels of IL-1beta, IL-6, and TNF-alpha and hepatic
      TNF-alpha mRNA level during fever in alpha(2)M -/- mice were compared with those
      in wild-type control mice. The alpha(2)M -/- mice developed a short-term markedly
      attenuated (ANOVA, P < 0.05) fever in response to LPS (2.5 mg/kg ip) compared
      with the wild-type mice. At 1.5 h after injection of LPS, the plasma
      concentration of TNF-alpha, but not IL-1beta or IL-6, was significantly lower (by
      58%) in the alpha(2)M -/- mice compared with their wild-type controls (ANOVA, P <
      0.05). There was no difference in hepatic TNF-alpha mRNA levels between alpha(2)M
      -/- and wild-type mice 1.5 h after injection of LPS. These data support the
      hypotheses that 1) alpha(2)M is important for the normal development of LPS
      induced fever and 2) a putative mechanism of alpha(2)M involvement in fever is
      through the inhibition of TNF-alpha clearance. These findings indicate a novel
      physiological role for alpha(2)M.

PMID- 12069949
TI  - Respiratory changes induced by kainic acid lesions in rostral ventral respiratory
      group of rabbits.
AB  - The role played by the Botzinger complex (BotC), the pre-Botzinger complex (pre
      BotC), and the more rostral extent of the inspiratory portion of the ventral
      respiratory group (iVRG) in the genesis of the eupneic pattern of breathing was
      investigated in anesthetized, vagotomized, paralyzed, and artificially ventilated
      rabbits by means of kainic acid (KA, 4.7 mM) microinjections (20-30 nl).
      Unilateral KA microinjections into all of the investigated VRG subregions caused
      increases in respiratory frequency associated with moderate decreases in peak
      phrenic amplitude in the BotC and pre-BotC regions. Bilateral KA microinjections
      into either the BotC or pre-BotC transiently eliminated respiratory rhythmicity
      and caused the appearance of tonic phrenic activity ("tonic apnea"), whereas
      injections into the rostral iVRG completely suppressed inspiratory activity.
      Rhythmic activity resumed as low-amplitude, high-frequency oscillations and
      displayed a progressive, although incomplete, recovery. Combined bilateral KA
      microinjections (BotC and pre-BotC) caused persistent (>3 h) tonic apnea. Results
      show that all of the investigated VRG subregions exert a potent control on both
      the intensity and frequency of inspiratory activity, thus suggesting that these
      areas play a major role in the genesis of the eupneic pattern of breathing.

PMID- 12069951
TI  - Consequences of load carrying by birds during short flights are found to be
      behavioral and not energetic.
AB  - The doubly-labeled water technique and video were used to measure the effect of
      mass loading on energy expenditure and takeoff performance in zebra finches,
      Taeniopygia guttata, that were making routine (nonalarm) short flights. Finches
      that carried 27% additional mass did not expend more energy during flight than
      unloaded controls. Carrying additional mass, however, led to a reduced body mass
      and a decreased velocity during takeoffs (by 12%). Calculations of instantaneous
      mechanical power indicated that energy expended by unloaded and loaded finches at
      takeoff was similar, due to the observed decrease in velocity by mass-loaded
      finches and a lowering of their body mass. During routine short flights, zebra
      finches appear to maintain their metabolic power input and mechanical power
      output regardless of mass loading. Here, the costs of carrying additional mass
      during routine short flights were revealed to be behavioral and not energetic.

PMID- 12069950
TI  - Renal endothelin in chronic angiotensin II hypertension.
AB  - To determine the influence of chronic ANG II infusion on urinary, plasma, and
      renal tissue levels of immunoreactive endothelin (ET), ANG II (65 ng/min) or
      saline vehicle was delivered via osmotic minipump in male Sprague-Dawley rats
      given either a high-salt diet (10% NaCl) or normal-salt diet (0.8% NaCl). High
      salt diet alone caused a slight but not statistically significant increase (7 +/-
      1%) in mean arterial pressure (MAP). MAP was significantly increased in ANG II
      infused rats (41 +/- 10%), and the increase in MAP was significantly greater in
      ANG II rats given a high-salt diet (59 +/- 1%) compared with the increase
      observed in rats given a high-salt diet alone or ANG II infusion and normal-salt
      diet. After a 2-wk treatment, urinary excretion of immunoreactive ET was
      significantly increased by approximately 50% in ANG II-infused animals and by
      over 250% in rats on high-salt diet, with or without ANG II infusion. ANG II
      infusion combined with high-salt diet significantly increased immunoreactive ET
      content in the cortex and outer medulla, but this effect was not observed in
      other groups. In contrast, high-salt diet, with or without ANG II infusion,
      significantly decreased immunoreactive ET content within the inner medulla. These
      data indicate that chronic elevations in ANG II levels and sodium intake
      differentially affect ET levels within the kidney and provide further support for
      the hypothesis that the hypertensive effects of ANG II may be due to interaction
      with the renal ET system.

PMID- 12069952
TI  - Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity.
AB  - We have recently demonstrated that natriuretic peptides (NPs), which are known
      for regulation of blood pressure via membrane guanylyl cyclase (GC) receptors,
      are lipolytic in human adipose tissue. In this study, we compared the NP control
      of lipolysis in adipocytes from humans, nonhuman primates (macaques), rodents
      (rats, mice, hamsters), and nonrodent mammals (rabbits, dogs). Isolated
      adipocytes from these species were exposed to increasing concentrations of atrial
      NP (ANP) or isoproterenol (beta-adrenergic agonist). Although isoproterenol was
      lipolytic in all of the species, ANP only enhanced lipolysis in human and macaque
      adipocytes. In primate fat cells, NP-induced lipolysis involved a cGMP-dependent
      pathway. Binding studies and real-time quantitative PCR assays revealed that rat
      adipocytes expressed a higher density of NP receptors compared with humans but
      with a different subtype pattern of expression; type-A GC receptors predominate
      in human fat cells. This was also confirmed by the weak GC-activity stimulation
      and the reduced cGMP formation under ANP exposure in rat adipocytes compared with
      human fat cells. In conclusion, NP-induced lipolysis is a primate specificity,
      and adipocytes from ANP-nonresponsive species present a predominance of
      "clearance" receptors and very low expression of "biologically active" receptors.

PMID- 12069954
TI  - ATP mediates tubuloglomerular feedback.

PMID- 12069953
TI  - Renal medullary nitric oxide deficit of Dahl S rats enhances hypertensive actions
      of angiotensin II.
AB  - Studies were designed to examine the hypothesis that the renal medulla of Dahl
      salt-sensitive (Dahl S) rats has a reduced capacity to generate nitric oxide
      (NO), which diminishes the ability to buffer against the chronic hypertensive
      effects of small elevations of circulating ANG II. NO synthase (NOS) activity in
      the outer medulla of Dahl S rats (arginine-citrulline conversion assay) was
      significantly reduced. This decrease in NOS activity was associated with the
      downregulation of protein expression of NOS I, NOS II, and NOS III isoforms in
      this region as determined by Western blot analysis. In anesthetized Dahl S rats,
      we observed that a low subpressor intravenous infusion of ANG II (5 ng. kg(-1).
      min(-1)) did not increase the concentration of NO in the renal medulla as
      measured by a microdialysis with oxyhemoglobin trapping technique. In contrast,
      ANG II produced a 38% increase in the concentration of NO (87 +/- 8 to 117 +/- 8
      nmol/l) in the outer medulla of Brown-Norway (BN) rats. The same intravenous dose
      of ANG II reduced renal medullary blood flow as determined by laser-Doppler
      flowmetry in Dahl S, but not in BN rats. A 7-day intravenous ANG II infusion at a
      dose of 3 ng. kg(-1). min(-1) did not change mean arterial pressure (MAP) in the
      BN rats but increased MAP in Dahl S rats from 120 +/- 2 to 138 +/- 2 mmHg (P <
      0.05). ANG II failed to increase MAP after NO substrate was provided by infusion
      of L-arginine (300 microg. kg(-1). min(-1)) into the renal medulla of Dahl S
      rats. Intravenous infusion of L-arginine at the same dose had no effect on the
      ANG II-induced hypertension. These results indicate that an impaired NO
      counterregulatory system in the outer medulla of Dahl S rats makes them more
      susceptible to the hypertensive actions of small elevations of ANG II.

PMID- 12069955
TI  - Adenosine mediates tubuloglomerular feedback.

PMID- 12069956
TI  - In vitro increase in chloroquine accumulation induced by dihydroethano- and
      ethenoanthracene derivatives in Plasmodium falciparum-parasitized erythrocytes.
AB  - The effects of a series of dihydroethano- and ethenoanthracene derivatives on
      chloroquine (CQ) accumulation in CQ-susceptible strain 3D7 and CQ-resistant clone
      W2 were assessed. The levels of CQ accumulation increased little or none in CQ
      susceptible strain 3D7 and generally increased markedly in CQ-resistant strain
      W2. At 10 microM, 28 compounds yielded cellular accumulation ratios (CARs)
      greater than that observed with CQ alone in W2. At 10 microM, in strain W2, 21 of
      31 compounds had CQ CARs two or more times higher than that of CQ alone, 15 of 31
      compounds had CQ CARs three or more times higher than that of CQ alone, 13 of 31
      compounds had CQ CARs four or more times higher than that of CQ alone, and 9 of
      31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1
      microM, 17 of 31 compounds had CQ CARs two or more times higher than that of CQ
      alone, 12 of 31 compounds had CQ CARs three or more times higher than that of CQ
      alone, 6 of 31 compounds had CQ CARs four or more times higher than that of CQ
      alone, and 3 of 31 compounds had CQ CARs five or more times higher than that of
      CQ alone. At 1 microM, 17 of 31 compounds were more potent inducers of CQ
      accumulation than verapamil and 12 of 31 compounds were more potent inducers of
      CQ accumulation than promethazine. The nature of the basic group seems to be
      associated with increases in the levels of CQ accumulation. At 1 and 10 microM,
      10 of 14 and 13 of 14 compounds with amino group (amines and diamines),
      respectively, had CARs >or=3, while at 1 and 10 microM, only 1 of the 13
      derivatives with amido groups had CARs >or=3. Among 12 of the 31 compounds which
      were more active inducers of CQ accumulation than promethazine at 1 microM, 10
      had amino groups and 1 had an amido group.

PMID- 12069957
TI  - Phagocytosis affects biguanide sensitivity of Acanthamoeba spp.
AB  - The incidence of Acanthamoeba keratitis, a disease associated with contact lens
      wear, has been in apparent decline with the advent of multipurpose contact lens
      solutions. The concentrations of the biguanides chlorhexidine digluconate (CHX)
      and particularly polyhexamethylene biguanide (PHMB) included in multipurpose
      solutions (MPSs) are sublethal for amoebae. We evaluated by flow cytometry the
      effects of these two biguanides on phagocytosis of particles and the survival of
      trophozoites of Acanthamoeba castellanii and A. polyphaga. Trophozoites of A.
      castellanii and A. polyphaga (10(6)/ml) were exposed to solutions of 5 and 50
      microg of PHMB and CHX per ml in the presence and absence of particles (i.e.,
      heat-killed yeasts and bacteria and latex beads). In addition, trophozoites were
      exposed to particles treated with these concentrations of the two biguanides. In
      the absence of particles, trophozoites of A. polyphaga appeared to be more
      resistant to the biguanides than those of A. castellanii. In the presence of
      particles, the rates of survival of both species were decreased. In most
      instances, particles treated with sublethal concentrations of both biguanides
      that were adsorbed onto the particles reduced the incidence of phagocytosis.
      Particles present in MPSs in contact lens cases may be involved in the decreased
      incidence of Acanthamoeba keratitis.

PMID- 12069958
TI  - Inhibition of nanobacteria by antimicrobial drugs as measured by a modified
      microdilution method.
AB  - Compounds from 16 classes of antimicrobial drugs were tested for their abilities
      to inhibit the in vitro multiplication of nanobacteria (NB), a newly discovered
      infectious agent found in human kidney stones and kidney cyst fluids from
      patients with polycystic kidney disease (PKD). Because NB form surface
      calcifications at physiologic levels of calcium and phosphate, they have been
      hypothesized to mediate the formation of tissue calcifications. We describe a
      modified microdilution inhibitory test that accommodates the unique growth
      conditions and long multiplication times of NB. This modified microdilution
      method included inoculation of 96-well plates and determination of inhibition by
      periodic measurement of the absorbance for 14 days in cell culture medium under
      cell culture conditions. Bactericidal or bacteriostatic drug effects were
      distinguished by subsequent subculture in drug-free media and monitoring for
      increasing absorbance. NB isolated from fetal bovine serum (FBS) were inhibited
      by tetracycline HCl, nitrofurantoin, trimethoprim, trimethoprim-sulfamethoxazole,
      and ampicillin at levels achievable in serum and urine; all drugs except
      ampicillin were cidal. Tetracycline also inhibited multiplication of isolates of
      NB from human kidney stones and kidney cyst fluids from patients with PKD. The
      other antibiotics tested against FBS-derived NB either had no effect or exhibited
      an inhibitory concentration above clinically achievable levels; the
      aminoglycosides and vancomycin were bacteriostatic. Antibiotic-induced
      morphological changes to NB were observed by electron microscopy.
      Bisphosphonates, aminocaproic acid, potassium citrate-citric acid solutions, and
      5-fluorouracil also inhibited the multiplication of NB in a cidal manner.
      Insights into the nature of NB, the action(s) of these drugs, and the role of NB
      in calcifying diseases may be gained by exploiting this in vitro inhibition test
      system.

PMID- 12069959
TI  - Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C
      reverse transcriptase (RT) and rapid development of resistance against
      nonnucleoside inhibitors of RT.
AB  - We sequenced and phylogenetically analyzed the reverse transcriptase (RT) region
      of five human immunodeficiency virus type 1 isolates from treatment-naive
      Ethiopian emigres to Israel. Heteroduplex mobility assays were performed to
      confirm the clade C status of env genomic regions. The RT sequences showed that
      the strains clustered phylogenetically with clade C viruses, and a KVEQ-specific
      motif of silent mutations (amino acids 65, 106, 138, and 161, respectively) at
      resistance sites was present in the polymerase region of all studied Ethiopian
      isolates and subtype C reference strains. In addition, many other silent
      mutations were observed in the clade C viruses at various resistance sites. In
      general, the Ethiopian isolates were more closely related genotypically to a
      clade C reference strain from Botswana (southern Africa) than to previously
      sequenced Ethiopian reference strains. Genotypic analysis showed that two
      Ethiopian isolates naturally harbored the mutations K70R and G190A associated
      with resistance to ZDV and nonnucleoside reverse transcriptase inhibitors,
      respectively. Phenotypic assays revealed that the K70R substitution in this
      context did not reduce susceptibility to ZDV, whereas the G190A substitution
      resulted in high-level resistance to nevirapine (NVP). Moreover, variants
      resistant to NVP, delavirdine (DLV), and efavirenz (EFV) were more rapidly
      selected at lower drug doses culture with clade C than with clade B wild-type
      isolates. In the case of subtype C, selection with NVP and/or EFV led to the
      appearance of several previously unseen mutations in RT, i.e., V106M and S98I, as
      well as other mutations that have been previously reported (e.g., K103N, V106A,
      V108I, and Y181C). After selection with DLV, a polymorphism, A62A, initially
      observed in the Ethiopian isolate 4762, mutated to A62V; the latter is a
      secondary substitution associated with multidrug resistance against nucleoside RT
      inhibitors. Phenotypic analysis of clade C mutants selected against NVP, DLV, and
      EFV revealed broad cross-resistance, particularly in regard to NVP and DLV. These
      findings suggest that RT genotypic diversity may influence the emergence of drug
      resistance.

PMID- 12069960
TI  - Comparative intracellular (THP-1 macrophage) and extracellular activities of beta
      lactams, azithromycin, gentamicin, and fluoroquinolones against Listeria
      monocytogenes at clinically relevant concentrations.
AB  - The activities of ampicillin, meropenem, azithromycin, gentamicin, ciprofloxacin,
      and moxifloxacin against intracellular hemolysin-positive Listeria monocytogenes
      were measured in human THP-1 macrophages and were compared with the extracellular
      activities observed in broth. All extracellular concentrations were adjusted to
      explore ranges that are clinically achievable in human serum upon conventional
      therapy. In broth, ampicillin, meropenem, and azithromycin were only
      bacteriostatic, whereas gentamicin, ciprofloxacin, and moxifloxacin were strongly
      bactericidal in a concentration-dependent manner. In cells, ampicillin,
      meropenem, azithromycin, and ciprofloxacin were slightly bactericidal (0.3- to
      0.8-log CFU reductions), moxifloxacin was strongly bactericidal (2.1-log CFU
      reduction), and gentamicin was virtually inactive. The difference in the
      efficacies of moxifloxacin and ciprofloxacin in cells did not result from a
      difference in levels of accumulation in cells (6.96 +/- 1.05 versus 7.75 +/-
      1.03) and was only partially explainable by the difference in the MICs (0.58 +/-
      0.04 versus 1.40 +/- 0.17 mg/liter). Further analysis showed that intracellular
      moxifloxacin expressed only approximately 1/7 of the activity demonstrated
      against extracellular bacteria and ciprofloxacin expressed only 1/15 of the
      activity demonstrated against extracellular bacteria. Gentamicin did not increase
      the intracellular activities of the other antibiotics tested. The data suggest
      (i) that moxifloxacin could be of potential interest for eradication of the
      intracellular forms of L. monocytogenes, (ii) that the cellular accumulation of
      an antibiotic is not the only determinant of its intracellular activity (for
      fluoroquinolones, it is actually a self-defeating process as far as activity is
      concerned), and (iii) that pharmacodynamics (activity-to-concentration
      relationships) need to be considered for the establishment of efficacy against
      intracellular bacteria, just as they are for the establishment of efficacy
      against extracellular infections.

PMID- 12069961
TI  - Design and activity of antimicrobial peptides against sporogonic-stage parasites
      causing murine malarias.
AB  - Insects produce several types of peptides to combat a broad spectrum of invasive
      pathogenic microbes, including protozoans. However, despite this defense
      response, infections are often established. Our aim was to design novel peptides
      that produce high rates of mortality among protozoa of the genus Plasmodium, the
      malaria parasites. Using existing antimicrobial peptide sequences as templates,
      we designed and synthesized three short novel hybrids, designated Vida1 to Vida3.
      Each has a slightly different predicted secondary structure. The peptides were
      tested against sporogonic stages of the rodent malaria parasites Plasmodium
      berghei (in vitro and in vivo) and P. yoelii nigeriensis (in vitro). The level of
      activity varied for each peptide and according to the parasite stage targeted.
      Vida3 (which is predicted to have large numbers of beta sheets and coils but no
      alpha helices) showed the highest level of activity, killing the early sporogonic
      stages in culture and causing highly significant reductions in the prevalence and
      intensity of infection of P. berghei after oral administration or injection in
      Anopheles gambiae mosquitoes. The secondary structures of these peptides may play
      a crucial role in their ability to interact with and kill sporogonic forms of the
      malaria parasite.

PMID- 12069962
TI  - In vitro activities of iboga alkaloid congeners coronaridine and 18
      methoxycoronaridine against Leishmania amazonensis.
AB  - In previous studies, we demonstrated the leishmanicide effect of coronaridine, a
      natural indole alkaloid isolated from stem bark of Peschiera australis (Delorenzi
      et al., Antimicrob. Agents Chemother. 45:1349-1354, 2001). In this study we show
      the leishmanicidal effect of the synthetic coronaridine and its racemic 18
      methoxylated analog, 18-methoxycoronaridine. Both alkaloids revealed a potent
      leishmanicide effect against Leishmania amazonensis, a causative agent of
      cutaneous and diffuse cutaneous leishmaniasis in the New World. Despite their
      potent leishmanicide effect, both alkaloids were neither toxic to murine
      macrophages nor did they modulate their oxidative or cytokine production
      responses.

PMID- 12069963
TI  - Enzymes associated with reductive activation and action of nitazoxanide,
      nitrofurans, and metronidazole in Helicobacter pylori.
AB  - Nitazoxanide (NTZ) is a redox-active nitrothiazolyl-salicylamide prodrug that
      kills Helicobacter pylori and also many anaerobic bacterial, protozoan, and
      helminthic species. Here we describe development and use of a spectrophotometric
      assay, based on nitroreduction of NTZ at 412 nm, to identify H. pylori enzymes
      responsible for its activation and mode of action. Three enzymes that reduce NTZ
      were identified: two related NADPH nitroreductases, which also mediate
      susceptibility to metronidazole (MTZ) (RdxA and FrxA), and pyruvate
      oxidoreductase (POR). Recombinant His-tagged RdxA, FrxA, and POR, overexpressed
      in nitroreductase-deficient Escherichia coli, each rapidly reduced NTZ, whereas
      only FrxA and to a lesser extent POR reduced nitrofuran substrates (furazolidone,
      nitrofurantoin, and nitrofurazone). POR exhibited no MTZ reductase activity
      either in extracts of H. pylori or following overexpression in E. coli; RdxA
      exhibited no nitrofuran reductase activity, and FrxA exhibited no MTZ reductase
      activity. Analysis of mutation to rifampin resistance (Rif(r)) indicated that NTZ
      was not mutagenic and that nitrofurans were only weakly mutagenic. Alkaline gel
      DNA electrophoresis indicated that none of these prodrugs caused DNA breakage. In
      contrast, MTZ caused DNA damage and was strongly mutagenic. We conclude that POR,
      an essential enzyme, is responsible for most or all of the bactericidal effects
      of NTZ against H. pylori. While loss-of-function mutations in rdxA and frxA
      produce a Mtz(r) phenotype, they do not contribute much to the innate
      susceptibility of H. pylori to NTZ or nitrofurans.

PMID- 12069964
TI  - CmeABC functions as a multidrug efflux system in Campylobacter jejuni.
AB  - Campylobacter jejuni, a gram-negative organism causing gastroenteritis in humans,
      is increasingly resistant to antibiotics. However, little is known about the drug
      efflux mechanisms in this pathogen. Here we characterized an efflux pump encoded
      by a three-gene operon (designated cmeABC) that contributes to multidrug
      resistance in C. jejuni 81-176. CmeABC shares significant sequence and structural
      homology with known tripartite multidrug efflux pumps in other gram-negative
      bacteria, and it consists of a periplasmic fusion protein (CmeA), an inner
      membrane efflux transporter belonging to the resistance-nodulation-cell division
      superfamily (CmeB), and an outer membrane protein (CmeC). Immunoblotting using
      CmeABC-specific antibodies demonstrated that cmeABC was expressed in wild-type 81
      176; however, an isogenic mutant (9B6) with a transposon insertion in the cmeB
      gene showed impaired production of CmeB and CmeC. Compared to wild-type 81-176,
      9B6 showed a 2- to 4,000-fold decrease in resistance to a range of antibiotics,
      heavy metals, bile salts, and other antimicrobial agents. Accumulation assays
      demonstrated that significantly more ethidium bromide and ciprofloxacin
      accumulated in mutant 9B6 than in wild-type 81-176. Addition of carbonyl cyanide
      m-chlorophenylhydrazone, an efflux pump inhibitor, increased the accumulation of
      ciprofloxacin in wild-type 81-176 to the level of mutant 9B6. PCR and
      immunoblotting analysis also showed that cmeABC was broadly distributed in
      various C. jejuni isolates and constitutively expressed in wild-type strains.
      Together, these findings formally establish that CmeABC functions as a tripartite
      multidrug efflux pump that contributes to the intrinsic resistance of C. jejuni
      to a broad range of structurally unrelated antimicrobial agents.

PMID- 12069965
TI  - Potential therapeutic role of cationic peptides in three experimental models of
      septic shock.
AB  - The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were
      investigated in three rat models of septic shock: (i) rats injected
      intraperitoneally with 10 microg of Escherichia coli O111:B4 lipopolysaccharide,
      (ii) rats given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia
      coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via
      cecal ligation and single puncture. All animals were randomized to receive
      parenterally isotonic sodium chloride solution, 1 mg of buforin II per kg of body
      weight, 1 mg of indolicidin per kg, 1 mg of KFFKFFKFF per kg, and 20 mg of
      imipenem per kg. The main outcome measures were bacterial growth in abdominal
      exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha)
      concentrations in plasma, and lethality. Treatment with all peptides resulted in
      significant reductions in plasma endotoxin and TNF-alpha concentrations compared
      with those resulting from the imipenem and saline treatments. On the other hand,
      imipenem treatment significantly reduced the levels of bacterial growth compared
      with the reductions achieved with the peptide and saline treatments. All
      compounds reduced the rates of death compared to that for the controls. Although
      the peptides demonstrated lower levels of antimicrobial activity than imipenem,
      they exhibited the dual properties of antimicrobial and antiendotoxin agents.

PMID- 12069966
TI  - Mn(III) pyrophosphate as an efficient tool for studying the mode of action of
      isoniazid on the InhA protein of Mycobacterium tuberculosis.
AB  - The antituberculosis drug isoniazid (INH) is quickly oxidized by stoichiometric
      amounts of manganese(III) pyrophosphate. In the presence of nicotinamide
      coenzymes (NAD+, NADH, nicotinamide mononucleotide [NMN+]) and nicotinic acid
      adenine dinucleotide (DNAD+), INH oxidation produced the formation of INH
      coenzyme adducts in addition to known biologically inactive products
      (isonicotinic acid, isonicotinamide, and isonicotinaldehyde). A pool of INH
      NAD(H) adducts preformed in solution allowed the rapid and strong inhibition of
      in vitro activity of the enoyl-acyl carrier protein reductase InhA, an INH target
      in the biosynthetic pathway of mycolic acids: the inhibition was 90 or 60% when
      the adducts were formed in the presence of NAD+ or NADH, respectively. Under
      similar conditions, no inhibitory activity of INH-NMN(H) and INH-DNAD(H) adducts
      was detected. When an isolated pool of 100 nM INH-NAD(H) adducts was first
      incubated with InhA, the enzyme activity was inhibited by 80%; when present in
      excess, both NADH and decenoyl-coenzyme A are able to prevent this phenomenon.
      InhA inhibition by several types of INH-coenzyme adducts coexisting in solution
      is discussed in relation with the structure of the coenzyme, the stereochemistry
      of the adducts, and their existence as both open and cyclic forms. Thus,
      manganese(III) pyrophosphate appears to be an efficient and convenient
      alternative oxidant to mimic the activity of the Mycobacterium tuberculosis KatG
      catalase-peroxidase and will be useful for further mechanistic studies of INH
      activation and for structural investigations of reactive INH species in order to
      promote the design of new inhibitors of InhA as potential antituberculous drugs.

PMID- 12069967
TI  - Molecular characterization of recombinant Pneumocystis carinii topoisomerase I:
      differential interactions with human topoisomerase I poisons and pentamidine.
AB  - The Pneumocystis carinii topoisomerase I-encoding gene has been cloned and
      sequenced, and the expressed enzyme interactions with several classes of
      topoisomerase I poisons have been characterized. The P. carinii topoisomerase I
      protein contains 763 amino acids and has a molecular mass of ca. 90 kDa. The
      expressed enzyme relaxes supercoiled DNA to completion and has no Mg2+
      requirement. Cleavage assays reveal that both the human and P. carinii enzymes
      form covalent complexes in the presence of camptothecin, Hoechst 33342, and the
      terbenzimidazole QS-II-48. As with the human enzyme, no cleavage is stimulated in
      the presence of 4',6'-diamidino-2-phenylindole (DAPI) or berenil. A yeast
      cytotoxicity assay shows that P. carinii topoisomerase I is also a cytotoxic
      target for the mixed intercalative plus minor-groove binding drug nogalamycin. In
      contrast to the human enzyme, P. carinii topoisomerase I is resistant to both
      nitidine and potent protoberberine human topoisomerase I poisons. The differences
      in the sensitivities of P. carinii and human topoisomerase I to various
      topoisomerase I poisons support the use of the fungal enzyme as a molecular
      target for drug development. Additionally, we have characterized the interaction
      of pentamidine with P. carinii topoisomerase I. We show, by catalytic inhibition,
      cleavage, and yeast cytotoxicity assays, that pentamidine does not target
      topoisomerase I.

PMID- 12069968
TI  - Multiplex PCR strategy for rapid identification of structural types and variants
      of the mec element in methicillin-resistant Staphylococcus aureus.
AB  - Full characterization of methicillin-resistant Staphylococcus aureus (MRSA)
      requires definition of not only the bacterial genetic background but also the
      structure of the complex and heterologous mec element these bacteria carry, which
      is associated with drug resistance determinant mecA. We report the development,
      validation, and application of a multiplex PCR strategy that allows quick
      presumptive characterization of the mec element types based on the structural
      features that were shown to be typical of mec elements carried by several MRSA
      clones. The strategy was validated by using a representative collection of
      pandemic MRSA clones in which the full structure of the associated mec elements
      was previously determined by hybridization and PCR screenings and also by DNA
      sequencing. The method was tested together with multilocus sequence typing and
      other typing methods for the characterization of 18 isolates representative of
      the MRSA clones recovered during a hospital outbreak in Barcelona, Spain. The
      multiplex PCR was shown to be rapid, robust, and capable in a single assay of
      identifying five structural types of the mec element among these strains, three
      major and two minor variants, each one of which has been already been seen among
      MRSA characterized earlier. This technique should be a useful addition to the
      armamentarium of molecular typing tools for the characterization of MRSA clonal
      types and for the rapid tentative identification of structural variants of the
      mec element.

PMID- 12069969
TI  - New carbenicillin-hydrolyzing beta-lactamase (CARB-7) from Vibrio cholerae non
      O1, non-O139 strains encoded by the VCR region of the V. cholerae genome.
AB  - In a previous study, an analysis of 77 ampicillin-nonsusceptible (resistant plus
      intermediate categories) strains of Vibrio cholerae non-O1, non-O139, isolated
      from aquatic environment and diarrheal stool, showed that all of them produced a
      beta-lactamase with a pI of 5.4. Hybridization or amplification by PCR with a
      probe for bla(TEM) or primers for bla(CARB) gene families was negative. In this
      work, an environmental ampicillin-resistant strain from this sample, ME11762,
      isolated from a waterway in the west region of Argentina, was studied. The
      nucleotide sequence of the structural gene of the beta-lactamase was determined
      by bidirectional sequencing of a Sau3AI fragment belonging to this isolate. The
      gene encodes a new 288-amino-acid protein, designated CARB-7, that shares 88.5%
      homology with the CARB-6 enzyme; an overall 83.2% homology with PSE-4, PSE-1,
      CARB-3, and the Proteus mirabilis N29 enzymes; and 79% homology with CARB-4
      enzyme. The gene for this beta-lactamase could not be transferred to Escherichia
      coli by conjugation. The nucleotide sequence of the flanking regions of the
      bla(CARB-7) gene showed the occurrence of three 123-bp V. cholerae repeated
      sequences, all of which were found outside the predicted open reading frame. The
      upstream fragment of the bla(CARB-7) gene shared 93% identity with a locus
      situated inside V. cholerae's chromosome 2. These results strongly suggest the
      chromosomal location of the bla(CARB-7) gene, making this the first communication
      of a beta-lactamase gene located on the VCR island of the V. cholerae genome.

PMID- 12069970
TI  - Amino acid residues essential for function of the MexF efflux pump protein of
      Pseudomonas aeruginosa.
AB  - At least four broad-spectrum efflux pumps (Mex) are involved in elevated
      intrinsic antibiotic resistance as well as in acquired multidrug resistance in
      Pseudomonas aeruginosa. Substrate specificity of the Mex pumps has been shown to
      be determined by the cytoplasmic membrane component (MexB, MexD, MexF, and MexY)
      of the tripartite efflux pump system. Alignment of their amino acid sequences
      with those of the homologous AcrB and AcrD pump proteins of Escherichia coli
      showed conservation of five charged amino acid residues located in or next to
      transmembrane segments (TMS). These residues were mutated in the MexF gene by
      site-directed mutagenesis and replaced by residues of opposite or neutral charge.
      MexF proteins containing combined D410A and A411G substitutions located in TMS4
      were completely inactive. Similarly, the substitutions E417K (next to TMS4) and
      K951E (TMS10) also caused loss of activity towards all tested antibiotics. The
      substitution E349K in TMS2 resulted in a MexF mutant protein which was unable to
      transport trimethoprim and quinolones but retained partial activity for the
      transport of chloramphenicol. All mutated MexF proteins were expressed at
      comparable levels when tested by Western blot analysis. It is concluded that
      charged residues located in or close to TMS are essential for proper function of
      MexF.

PMID- 12069971
TI  - Combination of quinupristin-dalfopristin and gentamicin against methicillin
      resistant Staphylococcus aureus: experimental rabbit endocarditis study.
AB  - The combination of quinupristin-dalfopristin (Q-D) and gentamicin was tested
      against two strains of gentamicin- and dalfopristin-susceptible methicillin
      resistant Staphylococcus aureus (MRSA). One strain was susceptible to macrolides,
      lincosamides, and streptogramin B type antibiotics (MLS(B)), and the other was
      constitutively resistant to these antibiotics by virtue of the ermA gene. The
      checkerboard method and time-kill curves showed that the combination of Q-D and
      gentamicin was indifferent. A rabbit endocarditis model simulated the
      pharmacokinetics achieved in humans receiving intravenous injections of Q-D (7.5
      mg/kg of body weight three times a day) and gentamicin (3 mg/kg once daily). For
      the MLS(B)-susceptible strain, a 4-day regimen reduced mean bacterial titers
      (MBT) in vegetations from 8.5 +/- 0.8 log CFU/g (control group) to 4.1 +/- 2.6
      (gentamicin), 3.0 +/- 0.9 (Q-D), and 2.6 +/- 0.5 log CFU/g (Q-D plus gentamicin).
      For the strain constitutively resistant to MLS(B), a 4-day regimen reduced MBT in
      vegetations from 8.7 +/- 0.9 log CFU/g (control group) to 5.0 +/- 2.2
      (gentamicin), 5.2 +/- 2.2 (Q-D), and 5.1 +/- 2.4 log CFU/g (Q-D plus gentamicin).
      The differences between control and treatment groups were significant for both
      strains (P < 0.0001), although there was no significant difference between
      treatment groups. No resistant variant was isolated from vegetations, and no
      significant difference in MBT in vegetations of treatment groups after 1-day
      regimens was observed. This experimental study found no additive benefit in
      combining Q-D and gentamicin against dalfopristin- and gentamicin-susceptible
      MRSA.

PMID- 12069972
TI  - ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human
      immunodeficiency virus type 1 reverse transcriptase.
AB  - Removal of nucleoside chain terminator inhibitors mediated by human
      immunodeficiency virus (HIV) reverse transcriptase (RT) using ATP as an acceptor
      molecule has been proposed as a novel mechanism of HIV resistance. Recombinant
      wild-type and mutant HIV type 1 (HIV-1) RT enzymes with thymidine analog
      resistance mutations D67N, K70R, and T215Y were analyzed for their ability to
      remove eight nucleoside reverse transcriptase inhibitors in the presence of
      physiological concentrations of ATP. The order for the rate of removal of the
      eight inhibitors by the mutant RT enzyme was zidovudine (AZT) > stavudine (d4T)
      >> zalcitabine (ddC) > abacavir > amdoxovir (DAPD) > lamivudine (3TC) >
      didanosine (ddI) > tenofovir. Thymidine analogs AZT and d4T were the most
      significantly removed by the mutant enzyme, suggesting that removal of these
      inhibitors by the ATP-dependent removal mechanism contributes to the AZT and d4T
      resistance observed in patients with HIV expressing thymidine analog resistance
      mutations. ATP-dependent removal of tenofovir was 22- to 35-fold less efficient
      than removal of d4T and AZT, respectively. The addition of ATP and the next
      complementary deoxynucleoside triphosphate caused a reduction of ATP-mediated
      removal of d4T, ddC, and DAPD, while AZT and abacavir removal was unaffected. The
      reduction of d4T, ddC, and DAPD removal in the presence of the deoxynucleoside
      triphosphate could explain the minor changes in susceptibility to these drugs
      observed in conventional in vitro phenotypic assays using cells that have higher
      deoxynucleoside triphosphate pools. The minimal removal of abacavir, ddC, DAPD,
      3TC, ddI, and tenofovir is consistent with the minor changes in susceptibility to
      these drugs observed for HIV mutants with thymidine analog resistance mutations.

PMID- 12069974
TI  - Experimental acute otitis media due to nontypeable Haemophilus influenzae:
      comparison of high and low azithromycin doses with placebo.
AB  - Treatment of acute otitis media (AOM) with azithromycin results in apparent
      clinical success, but tympanocentesis performed 4 to 6 days after initiation of
      therapy in children with nontypeable Haemophilus influenzae (NTHI) recovered from
      initial middle ear cultures demonstrates persistence of infection in more than
      50% of episodes. We sought to determine the effect of azithromycin at different
      doses on the density of middle ear infection due to NTHI to provide additional
      understanding of this dichotomy between clinical and microbiologic outcome
      measures in AOM. In a chinchilla model of experimental otitis media (EOM),
      animals treated with placebo were compared to animals receiving a single daily
      dose 30 or 120 mg of azithromycin per kg of body weight per day for 5 days.
      Microbiologic outcome was assessed by obtaining quantitative cultures from the
      middle ear during a 5-day course and for 1 week following therapy. Azithromycin
      concentrations were measured to ascertain whether a concentration-dependent
      effect was present. Azithromycin at 30 and 120 mg/kg/day demonstrated a dose
      dependent effect on the quantitative assessment of middle ear infection due to
      NTHI. A 30-mg/kg dose of azithromycin daily resulted in levels in serum and areas
      under the serum concentration-time curve at 24 h comparable to published data
      obtained with children given azithromycin at 5 to 10 mg/kg in multiday regimens.
      Increased doses of azithromycin (120 mg/kg) achieved 2.5- to 4-fold-higher levels
      in serum and 3- to 6-fold-higher total levels and levels in extracellular middle
      ear fluid as well as more rapid reduction in bacterial density and a greater
      proportion of middle ears with complete sterilization than either placebo or the
      30-mg/kg/day regimen.

PMID- 12069973
TI  - Antiretrovirus activity of a novel class of acyclic pyrimidine nucleoside
      phosphonates.
AB  - A novel class of acyclic nucleoside phosphonates has been discovered in which the
      base consists of a pyrimidine preferably containing an amino group at C-2 and C-4
      and a 2-(phosphonomethoxy)ethoxy (PMEO) or a 2-(phosphonomethoxy)propoxy (PMPO)
      group at C-6. The 6-PMEO 2,4-diaminopyrimidine (compound 1) and 6-PMPO 2,4
      diaminopyrimidine (compound 11) derivatives showed potent activity against human
      immunodeficiency virus (HIV) in the laboratory (i.e., CEM and MT-4 cells) and in
      primary (i.e., peripheral blood lymphocyte and monocyte/macrophage) cell cultures
      and pronounced activity against Moloney murine sarcoma virus in newborn NMRI
      mice. Their in vitro and in vivo antiretroviral activity was comparable to that
      of reference compounds 9-[(2-phosphonomethoxy)ethyl]adenine (adefovir) and (R)-9
      [(2-phosphonomethoxy)-propyl]adenine (tenofovir), and the enantiospecificity of
      (R)- and (S)-PMPO pyrimidine derivatives as regards their antiretroviral activity
      was identical to that of the classical (R)- and (S)-9-(2-phosphonomethoxy)propyl
      purine derivatives. The prototype PMEO and PMPO pyrimidine analogues were
      relatively nontoxic in cell culture and did not markedly interfere with host cell
      macromolecular (i.e., DNA, RNA, or protein) synthesis. Compounds 1 and 11 should
      be considered attractive novel pyrimidine nucleotide phosphonate analogues to be
      further pursued for their potential as antiretroviral agents in the clinical
      setting.

PMID- 12069975
TI  - Resistance to quinupristin-dalfopristin due to mutation of L22 ribosomal protein
      in Staphylococcus aureus.
AB  - The mechanism of resistance to the streptogramin antibiotics quinupristin and
      dalfopristin was studied in a Staphylococcus aureus clinical isolate selected
      under quinupristin-dalfopristin therapy, in four derivatives of S. aureus RN4220
      selected in vitro, and in a mutant selected in a model of rabbit aortic
      endocarditis. For all strains the MICs of erythromycin, quinupristin, and
      quinupristin-dalfopristin were higher than those for the parental strains but the
      MICs of dalfopristin and lincomycin were similar. Portions of genes for domains
      II and V of 23S rRNA and the genes for ribosomal proteins L4 and L22 were
      amplified and sequenced. All mutants contained insertions or deletions in a
      protruding beta hairpin that is part of the conserved C terminus of the L22
      protein and that interacts with 23S rRNA. Susceptible S. aureus RN4220 was
      transformed with plasmid DNA encoding the L22 alteration, resulting in
      transformants that were erythromycin and quinupristin resistant. Synergistic
      ribosomal binding of streptogramins A and B, studied by analyzing the
      fluorescence kinetics of pristinamycin I(A)-ribosome complexes, was abolished in
      the mutant strain, providing an explanation for quinupristin-dalfopristin
      resistance.

PMID- 12069976
TI  - Diversity of beta-lactam resistance-conferring amino acid substitutions in
      penicillin-binding protein 3 of Haemophilus influenzae.
AB  - The sequences of the ftsI gene, encoding the transpeptidase domain of penicillin
      binding protein (PBP) 3A and/or PBP 3B, which are involved in septal
      peptidoglycan synthesis, were determined for 108 clinical strains of Haemophilus
      influenzae with reduced susceptibility to beta-lactam antibiotics with or without
      beta-lactamase production and were compared to those of the ampicillin
      susceptible Rd strain and ampicillin-susceptible clinical isolates. The sequences
      have 18 different mutation patterns and were classified into two groups on the
      basis of amino acid substitutions deduced from the nucleotide sequences located
      between bp 960 and 1618 of the ftsI gene. In group I strains (n = 7), His-517 was
      substituted for Arg-517. In group II strains (n = 101), Lys-526 was substituted
      for Asn-526. In subgroup IIa (n = 5; H. influenzae ATCC 49247), the only observed
      substitution was Lys-526 for Asn-526; in subgroup IIb (n = 56), Val-502 was
      substituted for Ala-502 (n = 13), along with several other substitutions: Asn-350
      for Asp-350 (n = 15), Asn-350 for Asp-350 and Glu-490 for Gly-490 (n = 14), and
      Asn-350 for Asp-350 and Ser-437 for Ala-437 (n = 5). In subgroup IIc (n = 25),
      Thr-502 was substituted for Ala-502. In subgroup IId, Val-449 was substituted for
      Ile-449 (n = 15). The MICs of beta-lactam antibiotics for the 108 strains were to
      8 to 16 times the MICs for susceptible strains. The strains, isolated from both
      adults and children, were analyzed for genetic relationship by pulsed-field gel
      electrophoresis and by determination of ftsI sequence phylogeny. Both analyses
      revealed the lack of clonality and the heterogeneity of the strains, but some
      clusters suggest the spread and/or persistence of a limited number of strains of
      the same pulsotype and pattern of amino acid substitutions. Reduced
      susceptibility to beta-lactam, brought about by mutations of the ftsI gene, is
      becoming a frequent phenomenon, affecting both strains that produce beta
      lactamase and those that do not. The level of resistance remains low but opens
      the way to greater resistance in the future.

PMID- 12069977
TI  - Physiologically based pharmacokinetic model for terbinafine in rats and humans.
AB  - The aim of this study was to develop a physiologically based pharmacokinetic (PB
      PK) model capable of describing and predicting terbinafine concentrations in
      plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and
      2 blood compartments was developed using concentration-time data for tissues from
      rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of
      body weight). It was assumed that all tissues except skin and testis tissues were
      well-stirred compartments with perfusion rate limitations. The uptake of
      terbinafine into skin and testis tissues was described by a PB-PK model which
      incorporates a membrane permeability rate limitation. The concentration-time data
      for terbinafine in human plasma and tissues were predicted by use of a scaled-up
      PB-PK model, which took oral absorption into consideration. The predictions
      obtained from the global PB-PK model for the concentration-time profile of
      terbinafine in human plasma and tissues were in close agreement with the observed
      concentration data for rats. The scaled-up PB-PK model provided an excellent
      prediction of published terbinafine concentration-time data obtained after the
      administration of single and multiple oral doses in humans. The estimated volume
      of distribution at steady state (V(ss)) obtained from the PB-PK model agreed with
      the reported value of 11 liters/kg. The apparent volume of distribution of
      terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively,
      of the V(ss) for humans, indicating that uptake into and redistribution from
      these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK
      model developed in this study was capable of accurately predicting the plasma and
      tissue terbinafine concentrations in both rats and humans and provides insight
      into the physiological factors that determine terbinafine disposition.

PMID- 12069978
TI  - Alterations in penicillin-binding protein 1A confer resistance to beta-lactam
      antibiotics in Helicobacter pylori.
AB  - Most Helicobacter pylori strains are susceptible to amoxicillin, an important
      component of combination therapies for H. pylori eradication. The isolation and
      initial characterization of the first reported stable amoxicillin-resistant
      clinical H. pylori isolate (the Hardenberg strain) have been published
      previously, but the underlying resistance mechanism was not described. Here we
      present evidence that the beta-lactam resistance of the Hardenberg strain results
      from a single amino acid substitution in HP0597, a penicillin-binding protein 1A
      (PBP1A) homolog of Escherichia coli. Replacement of the wild-type HP0597 (pbp1A)
      gene of the amoxicillin-sensitive (Amx(s)) H. pylori strain 1061 by the
      Hardenberg pbp1A gene resulted in a 100-fold increase in the MIC of amoxicillin.
      Sequence analysis of pbp1A of the Hardenberg strain, the Amx(s) H. pylori strain
      1061, and four amoxicillin-resistant (Amx(r)) 1061 transformants revealed a few
      amino acid substitutions, of which only a single Ser(414)-->Arg substitution was
      involved in amoxicillin resistance. Although we cannot exclude that mutations in
      other genes are required for high-level amoxicillin resistance of the Hardenberg
      strain, this amino acid substitution in PBP1A resulted in an increased MIC of
      amoxicillin that was almost identical to that for the original Hardenberg strain.

PMID- 12069979
TI  - Antifungal triazoles and polymorphonuclear leukocytes synergize to cause
      increased hyphal damage to Scedosporium prolificans and Scedosporium apiospermum.
AB  - Scedosporium prolificans and Scedosporium apiospermum (Pseudallescheria boydii)
      cause pulmonary and disseminated infections refractory to most currently used
      antifungal agents in immunocompromised patients. We therefore investigated the
      potential antifungal activities of the triazoles itraconazole (ITC), voriconazole
      (VRC), and posaconazole (PSC) in combination with human polymorphonuclear
      leukocytes (PMNs) against the hyphae of these fungal pathogens. A colorimetric
      assay with (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]2H-tetrazolium-5
      carboxanilide) sodium salt was used for the measurement of hyphal damage as an
      indicator of antifungal activity. We found that the newer triazoles VRC and PSC
      displayed synergistic effects with PMNs against S. prolificans hyphae after 24 h
      (P < 0.05), whereas the effect of ITC in combination with PMNs was additive (P <
      0.01). All three triazoles displayed additive antifungal activities in
      combination with PMNs against S. apiospermum hyphae (P < 0.05). The synergistic
      or additive effects that these triazoles exhibited, combined with the antifungal
      activities of human PMNs, may have important therapeutic implications for the
      management of infections due to S. prolificans and S. apiospermum.

PMID- 12069980
TI  - Acyclovir cream for treatment of herpes simplex labialis: results of two
      randomized, double-blind, vehicle-controlled, multicenter clinical trials.
AB  - Acyclovir cream has been available for the treatment of herpes labialis in
      numerous countries outside the United States for over a decade. Evidence for its
      efficacy comes from a few small clinical trials conducted in the 1980s. To
      examine more comprehensively the efficacy and safety of this formulation, we
      conducted two independent, identical, parallel, randomized, double-blind, vehicle
      controlled, large-scale multicenter clinical trials. Healthy adults with a
      history of frequent herpes labialis were recruited from the general population,
      screened for eligibility, randomized equally to 5% acyclovir cream or vehicle
      control, given study medication, and told to self-initiate treatment five times
      daily for 4 days beginning within 1 h of the onset of a recurrent episode. The
      number of patients who treated a lesion was 686 in study 1 and 699 in study 2. In
      study 1, the mean duration of episodes was 4.3 days for patients treated with
      acyclovir cream and 4.8 days for those treated with the vehicle control (hazards
      ratio [HR] = 1.23; 95% confidence interval [CI], 1.06 to 1.44; P = 0.007). In
      study 2, the mean duration of episodes was 4.6 days for patients treated with
      acyclovir cream and 5.2 days for those treated with the vehicle control (HR =
      1.24; 95% CI, 1.06 to 1.44; P = 0.006). Efficacy was apparent whether therapy was
      initiated "early" (prodrome or erythema lesion stage) or "late" (papule or
      vesicle stage). There was a statistically significant reduction in the duration
      of lesion pain in both studies. Acyclovir cream did not prevent the development
      of classical lesions (progression to vesicles, ulcers, and/or crusts). Adverse
      events were mild and infrequent.

PMID- 12069982
TI  - In vitro antiviral interaction of lopinavir with other protease inhibitors.
AB  - The in vitro inhibition of wild-type human immunodeficiency virus (HIV) by
      combinations of lopinavir and six other protease inhibitors over a range of two
      drug combination ratios was evaluated. Combinations of lopinavir with indinavir,
      nelfinavir, amprenavir, tipranavir, and BMS-232632 generally displayed an
      additive relationship. In contrast, a consistent, statistically significant
      synergistic inhibition of HIV type 1 replication with combinations of lopinavir
      and saquinavir was observed. Analysis of the combination indices indicated that
      lopinavir with saquinavir was synergistic over the entire range of drug
      combination ratios tested and at all levels of inhibition in excess of 40%.
      Cellular toxicity was not observed at the highest drug concentrations tested.
      These results suggest that administration of combinations of the appropriate dose
      of lopinavir with other protease inhibitors in vivo may result in enhanced
      antiviral activity with no associated increase in cellular cytotoxicity. More
      importantly, the observed in vitro synergy between lopinavir and saquinavir
      provides a theoretical basis for the clinical exploration of a novel regimen of
      lopinavir-ritonavir and saquinavir.

PMID- 12069981
TI  - Pharmacodynamic effects of nitroimidazoles alone and in combination with
      clarithromycin on Helicobacter pylori.
AB  - Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and
      tinidazole alone and in combination with clarithromycin were performed by
      bioluminescence assay of intracellular ATP. The pharmacodynamic parameter control
      related effective regrowth time (CERT) was used. CERT is defined as the time
      required for the resumption of logarithmic growth and a return of the level of
      growth to the preexposure inoculum in the test culture minus the corresponding
      time in the control culture. CERT measures the combined effects of the initial
      level of killing and postantibiotic effect. The incubation times and drug
      concentrations were chosen according to their half-lives and their clinically
      achievable concentrations. The study shows that the parameter CERT is useful for
      the testing of antibiotic combinations. The CERTs induced by clarithromycin,
      metronidazole, and tinidazole alone and in the combinations tested were
      concentration dependent, with no maximum response, indicating that the use of
      high doses may be preferable. The combinations with the highest concentrations
      induced synergistic effects and prevented regrowth. The use of tinidazole in
      combination with clarithromycin proved to give the longest CERTs, indicating that
      this is the most effective combination.

PMID- 12069983
TI  - Pressure of zidovudine accelerates the reversion of lamivudine resistance
      conferring M184V mutation in the reverse transcriptase of human immunodeficiency
      virus type 1.
AB  - We cultured lamivudine-resistant human immunodeficiency virus type 1 (HIV-1)
      variants over an extended period of time in the presence of zidovudine and
      observed a premature reversion of the resistance-conferring M184V mutation. These
      data suggest that the presence of ZDV amplifies differences in replication
      capacity between wild-type HIV-1 and the mutant variant.

PMID- 12069984
TI  - Novel class 1 integron (InS21) carrying blaCTX-M-2 in Salmonella enterica serovar
      infantis.
AB  - The genetic organization of the region coding for CTX-M-2 in Salmonella enterica
      serovar Infantis was determined by PCR mapping. This gene seems to have been
      mobilized from the Kluyvera ascorbata chromosome to a complex sulI-type integron,
      similar to In6 and In7.

PMID- 12069985
TI  - Novel plasmid-encoded class C beta-lactamase (MOX-2) in Klebsiella pneumoniae
      from Greece.
AB  - Klebsiella pneumoniae KOL, a clinical strain resistant to various beta-lactams,
      was isolated from the stools of a patient from Greece. This strain harbored a new
      pI 9.1 plasmid-mediated AmpC beta-lactamase with unusually high levels of
      hydrolytic activity for cefoxitin and cefotetan that we named MOX-2. Sequencing
      of bla(MOX-2) revealed 93.2, 92.9, 92.7, and 73.1% identities with the deduced
      amino acid sequences of CMY-8, MOX-1, CMY-1, and the AmpC beta-lactamase of
      Aeromonas sobria, respectively.

PMID- 12069986
TI  - Inhibition of penicillinase by epigallocatechin gallate resulting in restoration
      of antibacterial activity of penicillin against penicillinase-producing
      Staphylococcus aureus.
AB  - The combination of epigallocatechin gallate (EGCg, a main constituent of tea
      catechins) with penicillin showed synergism against 21 clinical isolates of
      penicillinase-producing Staphylococcus aureus. Besides binding directly to
      peptidoglycan, the inhibition of penicillinase activity by EGCg is responsible
      for the synergism. EGCg inhibited the penicillinase activity in a dose-dependent
      fashion, with a 50% inhibitory concentration of 10 microg/ml.

PMID- 12069987
TI  - Fluorescence assay for studying the ability of macrolides to induce production of
      ribosomal methylase.
AB  - A screening assay to test the inducing capacity of macrolides by fusing the
      attenuator of the inducible erm(B) gene from Streptococcus pneumoniae HM28 with
      the gfpmut1 gene has been designed. Fluorescence was detected under UV light
      around disks impregnated with inducer macrolides (erythromycin or azithromycin)
      but not with noninducer ketolides. Induction could be quantified by fluorometry.

PMID- 12069988
TI  - Efficacy of liposomal amphotericin B in treatment of systemic murine fusariosis.
AB  - We have compared the activities of liposomal amphotericin B (LAMB) at 3, 5, 10,
      and 20 mg/kg/day and amphotericin B deoxycholate (AMB) at 1.5 and 2.5 mg/kg/day
      in a murine systemic infection by Fusarium verticillioides. Survival was improved
      by all treatments except AMB at 1.5 mg/kg/day. The tissue burden in liver was
      reduced by LAMB at all dosages and by AMB at 2.5 mg/kg/day. The two highest
      dosages of LAMB showed significant reductions in the spleen.

PMID- 12069989
TI  - Novel ciprofloxacin-resistant, nalidixic acid-susceptible mutant of
      Staphylococcus aureus.
AB  - A ciprofloxacin-resistant, nalidixic acid-susceptible mutant of Staphylococcus
      aureus (F145) contained no mutations within gyrA, gyrB, grlA, and grlB or within
      norA or its promoter region. MICs and accumulation studies suggest the role of a
      novel multidrug efflux pump.

PMID- 12069990
TI  - Structure-function relationship studies on the frog skin antimicrobial peptide
      tigerinin 1: design of analogs with improved activity and their action on
      clinical bacterial isolates.
AB  - Structure-function relationships in antimicrobial peptides have been extensively
      investigated in order to obtain improved analogs. Most of these studies have
      targeted either alpha-helical peptides or beta-sheet peptides with multiple
      disulfide bridges. Tigerinins are short, nonhelical antimicrobial peptides with a
      single disulfide bridge. In this study, we have synthesized several analogs of
      tigerinin 1 with an aim to understand the structural basis of activity as well as
      improve its activity. The studies demonstrate that the loop structure of
      tigerinin 1 is essential for its optimal activity. However, linearization with
      increased cationic charges can compensate for loss of loop structure to some
      extent. Morphology of the cells after treatment with the active analogs shows
      extensive leakage of cytoplasmic contents. Tigerinin 1 and two of its analogs
      exhibit impressive activity against a variety of clinical bacterial isolates.

PMID- 12069991
TI  - GF120918, a P-glycoprotein modulator, increases the concentration of unbound
      amprenavir in the central nervous system in rats.
AB  - The goal of this study was to determine the distribution of unbound amprenavir in
      the central nervous system (CNS) of rats. The concentration of unbound amprenavir
      in the extracellular fluid of the brain and the blood was examined in the
      presence and absence of the MDR modulator GF120918 by microdialysis. The brain-to
      blood ratio of amprenavir in the absence and presence of GF120918 was found to be
      significantly different (P < 0.003; 0.076 and 0.617, respectively). The use of
      the MDR modulator GF120918 could potentially increase the penetration of human
      immunodeficiency virus protease inhibitors into the CNS.

PMID- 12069994
TI  - Comparison of corticosteroids for treatment of respiratory syncytial virus
      bronchiolitis and pneumonia in cotton rats.
AB  - Triamcinolone acetonide, methylprednisolone, and dexamethasone were each
      evaluated in combination with palivizumab (Synagis) for the therapy of
      established respiratory syncytial virus infection in the cotton rat.
      Triamcinolone and methylprednisolone proved to be more effective than
      dexamethasone in reducing lung pathology. No recurrence of viral replication or
      pulmonary pathology followed the cessation of therapy.

PMID- 12069992
TI  - Neuroprotection and reduced proliferation of microglia in ribavirin-treated
      bornavirus-infected rats.
AB  - In a rat model of Borna disease, intracerebral ribavirin caused clinical
      improvement without changes in virus titer or nucleic acid. Levels of microglia
      and infiltrating CD4 and CD8 cells were decreased, despite increases in mRNAs
      encoding interleukin-1beta (IL-1beta), IL-10, and gamma interferon in the brain.
      Intracerebral ribavirin may reduce morbidity through effects on microglia cell
      proliferation.

PMID- 12069995
TI  - blaCTX-M-2 is located in an unusual class 1 integron (In35) which includes
      Orf513.
AB  - Examination of the bla(CTX-M-2) gene in plasmid pMAR-12 by sequencing and PCR
      analysis revealed that the bla gene and the surrounding DNA, which is closely
      related (99% homology) to the Kluyvera ascorbata chromosomal DNA that contains
      the bla(KLUA-1) gene, are located in a complex sul1-type integron, termed In35,
      that includes Orf513. It is possible that bla(CTX-M-2) was acquired by plasmid
      pMAR-12 through an uncharacterized recombinational event in which Orf513 could be
      involved.

PMID- 12069993
TI  - Comparative in vitro sensitivities of human immune cell lines, vaginal and
      cervical epithelial cell lines, and primary cells to candidate microbicides
      nonoxynol 9, C31G, and sodium dodecyl sulfate.
AB  - In experiments to assess the in vitro impact of the candidate microbicides
      nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and
      epithelial cell viability, cell lines and primary cell populations of lymphocytic
      and monocytic origin were generally shown to be equally sensitive to exposures
      ranging from 10 min to 48 h. However, U-937 cells were more sensitive to N-9 and
      C31G after 48 h than were primary monocyte-derived macrophages. Cytokine
      activation of monocytes and lymphocytes had no effect on cell viability following
      exposure to these microbicidal compounds. Primary and passaged vaginal epithelial
      cultures and cell lines differed in sensitivity to N-9 and C31G but not SDS.
      These studies provide a foundation for in vitro experiments in which cell lines
      of human immune and epithelial origin can be used as suitable surrogates for
      primary cells to further investigate the effects of microbicides on cell
      metabolism, membrane composition, and integrity and the effects of cell type,
      proliferation, and differentiation on microbicide sensitivity.

PMID- 12069996
TI  - Antibiotic susceptibilities of 96 isolates of Bacillus anthracis isolated in
      France between 1994 and 2000.
AB  - Ninety-six isolates of Bacillus anthracis recovered in France between 1994 and
      2000 were tested for their susceptibilities to 25 different antibiotics.
      Resistance to penicillin G and amoxicillin was 11.5%. All of the isolates were
      resistant to cotrimoxazole and susceptible to doxycycline, ciprofloxacin,
      pefloxacin, levofloxacin, teicoplanin, vancomycin, clindamycin, imipenem, and
      rifampin.

PMID- 12069997
TI  - In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse
      model.
AB  - The in vivo activities of posaconazole, itraconazole, and amphotericin B in
      neutropenic mice with zygomycosis were compared. The in vitro MICs of
      posaconazole and itraconazole for the strains of Mucor spp. used in this study
      ranged from 0.125 to 8 microg/ml and 0.25 to 8 microg/ml, respectively. The in
      vitro MIC range for amphotericin B is 0.125 to 0.25 microg/ml. At twice-daily
      doses of >or=15 mg/kg of body weight, posaconazole prolonged the survival of the
      mice and reduced tissue burden.

PMID- 12069998
TI  - Clotting in whole blood: analysis of a biochemical reaction network.

PMID- 12069999
TI  - Radiosensitization of recipient stem cells promotes engraftment.

PMID- 12070000
TI  - Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses.
AB  - Factor V Leiden (FVL) is associated with venous thrombosis; however, an
      association between FVL and arterial thrombosis remains controversial. We
      investigated FVL as a risk factor for myocardial infarction (MI), ischemic stroke
      (IS), or non-MI ischemic heart disease (non-MI-IHD). The design was 3 case
      control studies and 3 prospective studies with 21 years' follow-up. The setting
      was the general population in Copenhagen, Denmark. The participants for The
      Copenhagen City Heart Study were 20- to 95-year-old participants without
      cardiovascular disease (control population, n = 7907) or participants diagnosed
      with MI (n = 469), IS (n = 231), or non-MI-IHD (n = 365). In addition, 3
      independent patient populations from Copenhagen University Hospital with MI (n =
      493), IS (n = 231), or non-MI-IHD (n = 448) were included. We measured FVL
      genotype; major cardiovascular risk factors; and MI, IS, and non-MI-IHD incidence
      and prevalence. Prevalences of FVL heterozygotes and homozygotes in control
      subjects from the general population were 7.7% and 0.2%. Odds ratios and relative
      risks of MI in FVL carriers (heterozygotes + homozygotes) versus noncarriers were
      1.24 (95% confidence interval [CI], 0.91-1.69) and 0.83 (0.58-1.20) in case
      control and prospective studies, respectively. Corresponding risks for IS were
      0.92 (95% CI, 0.56-1.53) and 0.68 (0.45-1.04), and for non-MI-IHD 1.01 (95% CI,
      0.71-1.44) and 0.97 (0.66-1.42). Findings from The Copenhagen City Heart Study
      suggest that FVL is not associated with MI, IS, or non-MI-IHD.

PMID- 12070001
TI  - Trafficking machinery of NKT cells: shared and differential chemokine receptor
      expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct
      cytokine-producing capacity.
AB  - Natural killer T (NKT) cells are important regulators of the immune system, but
      their trafficking machinery, including expression of chemokine receptors, has
      been poorly defined. Unlike other conventional T-cell populations, we show that
      most NKT cells express receptors for extralymphoid tissue or inflammation-related
      chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue
      homing chemokine receptors (CCR7 and CXCR5). A population with homing potential
      for lymph nodes (L selectin(+) CCR7(+)) exists only within a small subset of CD4
      NKT cells. We show differential expression of chemokine receptors among NKT cell
      subsets: CCR4 is mainly expressed by a high cytokine (interleukin-4/interleukin
      2)-producing (CD4) NKT subset, while CCR1, CCR6, and CXCR6 are preferentially
      expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets. In line
      with this, TARC/CCL17 (a CCR4 ligand) induces preferential chemotaxis of the CD4
      NKT subset, while chemotactic activities of LARC/CCL20 (a CCR6 ligand) and MIP-1
      alpha/CCL3 (a CCR1 ligand) are focused on the CD8 and CD4(-)CD8(-) NKT cells. We
      conclude that, unlike conventional naive, memory, or effector T cells, the entire
      NKT cell population expresses nonlymphoid tissue homing chemokine receptors, yet
      NKT cell subsets differ considerably from each other by displaying distinct and
      reciprocal expression patterns of some chemokine receptors. Our results identify
      chemokine receptors that are potentially important for trafficking of human blood
      NKT cell subsets and reveal their function (cytokine production capacity)
      dependent differential trafficking potentials.

PMID- 12070002
TI  - Effects of iron overload and hepatitis C virus positivity in determining
      progression of liver fibrosis in thalassemia following bone marrow
      transplantation.
AB  - To identify the role of iron overload in the natural history of liver fibrosis,
      we reviewed serial hepatic biopsy specimens taken annually from patients cured of
      thalassemia major by bone marrow transplantation. The patients underwent
      transplantation between 1983 and 1989 and did not receive any chelation or
      antiviral therapy. Two hundred eleven patients (mean age, 8.7 +/- 4 years) were
      evaluated for a median follow-up of 64 months (interquartile range, 43-98 months)
      by a median number of 5 (interquartile range, 3-6) biopsy samples per patient.
      Hepatic iron concentration was stratified by tertiles (lower, 0.5-5.6 mg/g;
      medium, 5.7-12.7 mg/g; upper, 12.8-40.6 mg/g dry weight). Forty-six (22%)
      patients showed signs of liver fibrosis progression; the median time to
      progression was 51 months (interquartile range, 36-83 months). In a multivariate
      Cox proportional hazard model, the risk for fibrosis progression correlated to
      medium hepatic iron content (hazard rate, 1.9; 95% confidence interval [CI], 0.74
      5.0), high hepatic iron content (hazard rate, 8.7; 95% CI, 3.6-21.0) and
      hepatitis C virus (HCV) infection (hazard rate, 3.1; 95% CI, 1.5-6.5). A striking
      increase in the risk for progression was found in the presence of both risk
      factors. None of the HCV-negative patients with hepatic iron content lower than
      16 mg/g dry weight showed fibrosis progression, whereas all the HCV-positive
      patients with hepatic iron concentration greater than 22 mg/g dry weight had
      fibrosis progression in a minimum follow-up of 4 years. Thus, iron overload and
      HCV infection are independent risk factors for liver fibrosis progression, and
      their concomitant presence results in a striking increase in risk.

PMID- 12070003
TI  - HLA class II haplotype and quantitation of WT1 RNA in Japanese patients with
      paroxysmal nocturnal hemoglobinuria.
AB  - It is unclear how a paroxysmal nocturnal hemoglobinuria (PNH) clone expands in
      bone marrow, although immune mechanisms involving cytotoxic T lymphocytes,
      autosomal proliferation, and apoptosis resistance have been hypothesized. To
      clarify aspects of immune mechanisms and proliferation of PNH cells, we
      investigated HLA-DRB1, -DQA1, and -DQB1 alleles by polymerase chain reaction
      (PCR)-based genotyping and expression of the Wilms' tumor gene, WT1, by real-time
      reverse transcriptase-PCR (RT-PCR) in 21 PNH and 21 aplastic anemia (AA)
      patients. HLA genotyping indicated that the frequency of DRB1*1501, DQA1*0102,
      and DQB1*0602 alleles in PNH patients and of DQB1*0602 allele in AA patients was
      significantly higher than in 916 Japanese controls, and that the HLA-DRB1*1501
      DQA1*0102-DQB1*0602 haplotype, found in 13 of 21 PNH patients, 5 of 7 AA-PNH
      syndrome patients, and 7 of 21 AA patients showed significant differences
      compared with healthy individuals. RT-PCR analysis showed that the mean values of
      WT1 RNA were 3413, 712, and 334 copies/microg RNA in PNH, AA, and healthy
      individuals, respectively. The values for PNH patients were significantly higher
      than for AA patients and healthy volunteers and were correlated with the
      proportion of CD16b(-) granulocytes. The high frequency of HLA-DRB1*1501
      DQA1*0102-DQB1*0602 haplotype in PNH, including AA-PNH syndrome, and AA patients
      suggests that linkage exists between the disorders and that immune mechanisms in
      an HLA-restricted manner play an important role in the pathogenesis of these
      disorders. In addition, high expression of WT1 RNA in PNH patients is related to
      a PNH clone, but it remains unclear whether this causes expansion of a PNH clone.

PMID- 12070004
TI  - Impact of trisomy 8 (+8) on clinical presentation, treatment response, and
      survival in acute myeloid leukemia: a Southwest Oncology Group study.
AB  - The prognostic impact of trisomy 8, alone or with other clonal aberrations, was
      evaluated in 849 patients with previously untreated acute myeloid leukemia (AML)
      who were registered to 5 Southwest Oncology Group trials. At presentation, 108
      (12.7%) patients had +8 in their karyotypes, including 43 (5.1%) patients with +8
      as the sole aberration; 307 (36.2%) were normal, and 434 (51.1%) had other
      cytogenetic abnormalities. Patients with +8 were slightly older (P =.033), had
      lower WBC (P =.011), and had lower percentages of peripheral blasts (P =.0004)
      than the patients without +8. Median survival time for all patients with +8 was
      9.9 months (95% CI, 6.5-12.5), similar to that of "unfavorable" cytogenetics risk
      groups (8.3 months; 95% CI, 6.8-9.5.) Patients with +8 had significantly lower
      peripheral blasts (P =.0002), WBC (P <.0001) counts, and decreased overall
      survival (OS) than patients with normal cytogenetics (9.9 months vs 15.4 months;
      P =.006). However, survival of patients with +8 as the sole aberration did not
      differ significantly from those with normal cytogenetics (P =.36). Thus, the
      trisomy 8 group as a whole had poor survival, which was largely attributable to
      worsened outcomes among patients whose trisomy 8 was associated with other
      unfavorable cytogenetic abnormalities.

PMID- 12070005
TI  - High numbers of active caspase 3-positive Reed-Sternberg cells in pretreatment
      biopsy specimens of patients with Hodgkin disease predict favorable clinical
      outcome.
AB  - In vitro studies suggest that resistance to the apoptosis-inducing effect of
      chemotherapy might explain poor responses to therapy in fatal instances of
      Hodgkin disease (HD). Execution of apoptosis depends on proper functioning of
      effector caspases, in particular caspase 3, which is activated on the induction
      of apoptosis through either the stress-induced pathway or the death receptor
      mediated pathway. Thus, high levels of caspase 3 activation should reflect proper
      functioning of one or both identified apoptosis pathways, resulting in
      chemotherapy-sensitive neoplastic cells and thus a favorable clinical response to
      chemotherapy. We tested this hypothesis by quantifying active caspase 3-positive
      tumor cells in primary biopsy specimens of HD and compared these numbers to
      clinical outcomes. Using an immunohistochemical assay, activation of caspase 3
      was detected in 0% to 13% of neoplastic cells. High numbers of active caspase 3
      positive tumor cells (5% or more) correlated with excellent clinical prognosis; 0
      of 22 patients with 5% or more active caspase 3-positive cells died compared with
      11 of 41 patients with less than 5% positive cells (P =.007). Proper functioning
      of active caspase 3 was demonstrated by the detection of one of its cleaved
      substrates, PARP-1/p89, in similar percentages of neoplastic cells. High levels
      of active caspase 3-positive neoplastic cells were associated with the expression
      of p53 and its downstream effector molecule p21, suggesting proper functioning of
      the stress-induced apoptosis pathway. In conclusion, high numbers of active
      caspase 3-positive neoplastic cells predict a highly favorable clinical outcome
      in HD patients, supporting the notion that an (at least partially) intact
      apoptosis cascade is essential for the cell killing effect of chemotherapy.

PMID- 12070006
TI  - Persistence of lymphoblasts in bone marrow on day 15 and days 22 to 25 of
      remission induction predicts a dismal treatment outcome in children with acute
      lymphoblastic leukemia.
AB  - We determined the prognostic importance of morphologically identifiable
      persistent disease at day 15 and days 22 to 25 of remission induction in
      childhood acute lymphoblastic leukemia (ALL). Among 546 patients entered on 2
      consecutive protocols, 397 patients had evaluable bone marrow (BM) examinations
      on day 15 (+/- 1 day) and 218 on days 22 to 25 (+/- 1 day). Fifty-seven patients
      (14%) had persistent lymphoblasts (> or = 1%) in the BM on day 15 and 27 patients
      (5.5%) had persistent lymphoblasts on days 22 to 25. The 5-year event-free
      survival (EFS) was significantly worse for patients with lymphoblasts on day 15
      (40% +/- 6%) or on days 22 to 25 (4% +/- 3%) as compared to those without
      lymphoblasts on these dates (78% +/- 2% and 76% +/- 2%, respectively, P <.001 for
      both comparisons). A worse prognosis was observed even for patients with a low
      percentage of lymphoblasts (ie, 1%-4%) at either day 15 (5-year EFS = 56% +/- 8%)
      or days 22 to 25 (5-year EFS = 0%) compared to those without morphologically
      identifiable persistent lymphoblasts at these times (P <.001 for both
      comparisons). The prognostic impact of persistent lymphoblasts on both dates
      remained significant after adjusting for other known risk factors, including
      treatment protocol, age, white blood cell count, DNA index, cell lineage, and
      central nervous system status, and National Cancer Institute/Rome criteria
      simultaneously. Hence, persistence of lymphoblasts (even 1%-4%) on day 15 of
      remission induction was associated with a poor prognosis and on days 22 to 25
      signified a particularly dismal outcome; these very high-risk patients require
      novel or more intensive therapy to improve outcome.

PMID- 12070007
TI  - Therapy for chronic graft-versus-host disease: a randomized trial comparing
      cyclosporine plus prednisone versus prednisone alone.
AB  - Results of previous studies have suggested that transplantation-related mortality
      among patients with chronic graft-versus-host disease (GVHD) may be reduced by
      combined treatment with cyclosporine (CSP) and prednisone rather than by
      prednisone alone. In a randomized trial, we assessed the efficacy of cyclosporine
      plus prednisone versus prednisone alone as initial therapy for chronic GHVD among
      patients whose platelet counts were higher than 100,000/microL. Prednisone was
      administered initially at a dose of 1.0 mg/kg per day orally, followed by a
      prolonged taper, and cyclosporine was administered at 6 mg/kg orally twice daily
      every other day. The cumulative incidence of transplantation-related mortality at
      5 years from enrollment was 17% (95% CI, 0.11-0.23) in the CSP plus prednisone
      arm and 13% (95% CI, 0.08-0.19) in the prednisone arm. The hazards of
      transplantation-related mortality, overall mortality, recurrent malignancy,
      secondary therapy, and discontinuation of all immunosuppressive therapy were not
      significantly different between the 2 arms, but survival without recurrent
      malignancy was lower in the 2-drug arm (P =.03). Avascular necrosis developed in
      18 (13%) of the 142 patients in the CSP plus prednisone arm and in 32 (22%) of
      the 145 patients in the prednisone arm (P =.04). Treatment with CSP plus
      prednisone may reduce the risk for steroid-related toxicity, but results of the
      current study do not substantiate the hypothesis that the administration of CSP
      reduces transplantation-related mortality among patients with chronic GVHD.

PMID- 12070008
TI  - Prognostic importance of measuring early clearance of leukemic cells by flow
      cytometry in childhood acute lymphoblastic leukemia.
AB  - Early clearance of leukemic cells is a favorable prognostic indicator in
      childhood acute lymphoblastic leukemia (ALL). However, identification of residual
      leukemic cells by their morphologic features is subjective and lacks sensitivity.
      To improve estimates of leukemia clearance, we applied flow cytometric techniques
      capable of detecting 1 leukemic cell in 10,000 or more normal cells and
      prospectively measured residual leukemia in bone marrow samples collected on day
      19 of remission-induction chemotherapy from 248 children with newly diagnosed
      ALL. In 134 samples (54.0%), we identified at least 0.01% leukemic cells (0.01%-<
      0.1% in 51 samples [20.6%], 0.1%-< 1% in 36 [14.5%], and > or = 1% in 47
      [19.0%]). Among 110 children treated within a single chemotherapy program, the 5
      year mean +/- SE cumulative incidence of relapse or failure to achieve remission
      was 32.2% +/- 6.5% for the 59 patients with 0.01% residual leukemic cells or
      greater on day 19 and 6.0% +/- 3.4% for the 51 patients with less than 0.01%
      leukemic cells (P <.001). The prognostic value of day-19 bone marrow status
      defined by flow cytometry was superior to that defined by morphologic studies and
      remained significant after adjustment for other clinical and biologic variables.
      Lack of detectable leukemic cells on day 19 was more closely associated with
      relapse-free survival than was lack of detectable residual disease at the end of
      remission induction (day 46). Thus, approximately half of the children with ALL
      achieve profound clearance of leukemic cells after 2 to 3 weeks of remission
      induction chemotherapy, and these patients have an excellent treatment outcome.

PMID- 12070009
TI  - Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia:
      correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and
      usefulness as a marker for the detection of minimal residual disease.
AB  - FLT3 length mutation (FLT3-LM) is a molecular marker potentially useful for the
      characterization of acute myeloid leukemia (AML). To evaluate the distribution of
      FLT3-LM within biologic subgroups, we screened 1003 patients with AML at
      diagnosis for this mutation. FLT3-LM was found in 234 (23.5%) of all patients and
      thus is the most frequent mutation in AML described so far. Of all positive
      patients, 165 (70.5%) revealed a normal karyotype. Of the 69 patients with
      chromosome aberrations, 24 (34.8%) had a t(15;17). The mutation was rare in AML
      with t(8;21), inv(16) 11q23 rearrangements, and complex karyotypes. FLT3-LM was
      not distributed equally within different French-American-British (FAB) subtypes
      and was correlated with a high peripheral blood count in FAB M1, M2, and M4 (P
      <.0001). In addition, the median age of patients with the mutation was lower
      (54.9 vs 57.6 years; P =.043), and, at a ratio of 1.36:1 (P =.023), the mutation
      was more frequent in females than in males. Within the AMLCG study, FLT3-LM was
      of intermediate prognostic significance. The complete remission rate of 70.3% in
      patients with FLT3-LM was similar to that (70.4%) in patients without FLT3-LM.
      Overall survival was not different between patients with or without FLT3-LM. In
      contrast, patients with FLT3-LM had a significantly shorter event-free survival
      (7.4 vs 12.6 months; P =.0072) because of a higher relapse rate. Besides the
      importance of FLT3-LM for biologic and clinical characterization of AML, we show
      its value as a marker for disease monitoring based on 120 follow-up samples of 34
      patients.

PMID- 12070010
TI  - Glutathione S-transferase genotypes, genetic susceptibility, and outcome of
      therapy in childhood acute lymphoblastic leukemia.
AB  - The glutathione S-transferase (GST) genes are involved in the metabolism of
      environmental carcinogens and of some classes of chemotherapy drugs. GSTM1 and
      GSTT1 genotypes are polymorphic in humans, and the phenotypic absence of enzyme
      activity is caused by a homozygous inherited deletion of the gene. Previous,
      smaller studies of childhood acute lymphoblastic leukemia (ALL) provided
      contrasting data on the role of the GST genotype in susceptibility and treatment
      outcomes. We analyzed GST genotypes in 710 children with ALL treated by the
      Children's Cancer Group. Frequencies were compared with those of normal controls,
      and outcomes were analyzed according to genotype. Comparisons of gene frequencies
      in ALL case and control patients showed similar frequencies (54% vs 53% GSTM1
      null in whites, P =.9; 40% versus 32% in blacks, P =.45; 16% versus 15% GSTT1
      null in whites, P =.8; 17% versus 28% in blacks, P =.3). ALL was not associated
      with the GSTM1-null genotype or the double-null genotype in blacks or whites, in
      contrast to previous reports. Stratification of cases by age at diagnosis, sex,
      white blood cell count at diagnosis, B or T lineage, or cytogenetics revealed no
      differences in genotype frequencies. Analysis of treatment outcomes showed no
      differences in outcome according to GST genotype; in particular, there were no
      differences in frequencies of relapse at any site. These data, representing a
      larger series than any reported previously, suggest that GST genotype does not
      affect etiology or outcome of childhood ALL.

PMID- 12070011
TI  - Retroviral transduction of IL2RG into CD34(+) cells from X-linked severe combined
      immunodeficiency patients permits human T- and B-cell development in sheep
      chimeras.
AB  - X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the
      common gamma chain of cytokine receptors, gamma(c). Because bone marrow
      transplantation (BMT) for XSCID does not provide complete immune reconstitution
      for many patients and because of the natural selective advantage conferred on
      lymphoid progenitors by the expression of normal gamma(c), XSCID is a good
      candidate disease for therapeutic retroviral gene transfer to hematopoietic stem
      cells. We studied XSCID patients who have persistent defects in B-cell and/or
      combined B- and T-cell function despite having received T cell-depleted
      haploidentical BMT. We compared transduction of autologous B-cell lines and
      granulocyte colony-stimulating factor-mobilized peripheral CD34(+) cells from
      these patients using an MFGS retrovirus vector containing the gamma(c) gene IL2RG
      pseudotyped with amphotropic, gibbon ape leukemia virus, or RD114 envelopes.
      Transduced B-cell lines and peripheral CD34(+) cells demonstrated provirus
      integration and new cell-surface gamma(c) expression. The chimeric sheep model
      was exploited to test development of XSCID CD34(+) cells into mature myeloid and
      lymphoid lineages. Transduced and untransduced XSCID CD34(+) cells injected into
      developing sheep fetuses gave rise to myeloid cells. However, only transduced
      gamma progenitors from XSCID patients developed into T and B cells. These results
      suggest that gene transfer to autologous peripheral CD34(+) cells using MFGS-gc
      retrovirus may benefit XSCID patients with persistent T- and B-cell deficits
      despite prior BMT.

PMID- 12070012
TI  - Transcriptional regulation of myeloid differentiation primary response (MyD)
      genes during myeloid differentiation is mediated by nuclear factor Y.
AB  - To understand the molecular mechanism by which interleukin-6 (IL-6) regulates
      myeloid differentiation primary response (MyD) genes at the onset of M1 myeloid
      differentiation, we used JunB as a representative MyD gene to isolate and
      characterize IL-6 responsive elements. An IL-6 responsive element was localized
      between -65 and -52 of the JunB promoter (-65/-52 IL-6RE). By using antibody and
      oligonucleotide competition assays in electrophoretic mobility shift assay
      experiments, we have shown that the heterotrimeric transcription nuclear factor Y
      (NF-Y) complex binds to this element. A dominant-negative form of NF-YA,
      ectopically expressed in M1 cells, blocked NF-Y binding to the -65/-52 IL-6RE and
      reduced induction of JunB by IL-6. Furthermore, inhibition of NF-Y binding also
      reduced MyD gene induction by IL-6 and dampened the IL-6-induced M1
      differentiation program. These findings are consistent with the observation that
      most MyD genes contain intact NF-Y binding motifs in their promoter regions. In
      contrast to M1 cells, during myeloid differentiation of bone marrow (BM), there
      was induction of NF-Y binding to the -65/-52 IL-6RE. This induced binding can be
      attributed to the observed induction of NF-YA protein expression and may reflect
      the molecular mechanism that couples proliferation to terminal differentiation of
      normal myeloblasts. Similar to M1 cells, blocking NF-Y binding in BM resulted in
      a reduction in mature macrophages. It can be concluded that NF-Y plays a role in
      the transcriptional regulation of MyD genes and is required for optimum myeloid
      differentiation.

PMID- 12070013
TI  - A human Mix-like homeobox gene MIXL shows functional similarity to Xenopus Mix.1.
AB  - Molecular events involved in specification of early hematopoietic system are not
      well known. In Xenopus, a paired-box homeodomain family (Mix.1-4) has been
      implicated in this process. Although Mix-like homeobox genes have been isolated
      from chicken (CMIX) and mice (Mml/MIXL1), isolation of a human Mix-like gene has
      remained elusive. We have recently isolated and characterized a novel human Mix
      like homeobox gene with a predicted open reading frame of 232 amino acids
      designated the Mix.1 homeobox (Xenopus laevis)-like gene (MIXL). The overall
      identity of this novel protein to CMIX and Mml/MIXL1 is 41% and 69%,
      respectively. However, the identity in the homeodomain is 66% to that of Xenopus
      Mix.1, 79% to that of CMIX, and 94% to that of Mml/MIXL1. In normal
      hematopoiesis, MIXL expression appears to be restricted to immature B- and T
      lymphoid cells. Several acute leukemic cell lines of B, T, and myeloid lineage
      express MIXL suggesting a survival/block in differentiation advantage.
      Furthermore, Xenopus animal cap assay revealed that MIXL could induce expression
      of the alpha-globin gene, suggesting a functional conservation of the
      homeodomain. Isolation of the MIXL gene is the first step toward understanding
      novel regulatory circuits in early hematopoietic differentiation and malignant
      transformation.

PMID- 12070014
TI  - Expression of the beta 4 integrin subunit induces monocytic differentiation of
      32D/v-Abl cells.
AB  - The alpha 6 beta 4 integrin is the receptor for various laminin isoforms and is a
      component of the hemidesmosome. Increased expression levels of this integrin
      correlate with the aggressive phenotype of many epithelial tumors compared with
      surrounding normal tissue. Furthermore, the long cytoplasmic tail of the beta 4
      integrin subunit has been implicated in several signal transduction pathways that
      are involved not only in invasion, but also in proliferation and apoptosis. Here
      we report that the exogenous expression of beta 4 integrin in 32D/v-abl
      transformed cells reduces tumor aggressiveness in vivo and strongly inhibits cell
      proliferation in vitro by inducing monocytic differentiation. These effects are
      accompanied by growth arrest and p73 protein accumulation. The hypothesis that
      the inhibition of v-Abl oncogenic capacity could allow the activation of the
      endogenous c-Abl was tested in RKO cells. The results clearly demonstrated a
      strong increase of c-Abl phosphorylation that is accompanied by its association
      with p73 protein. Overall, the reported findings indicate that alpha 6 beta 4
      integrin promotes growth arrest and differentiation by modulating Abl kinases and
      p73 protein pathway(s).

PMID- 12070015
TI  - Novel transcription factors in human CD34 antigen-positive hematopoietic cells.
AB  - Transcription factors (TFs) and the regulatory proteins that control them play
      key roles in hematopoiesis, controlling basic processes of cell growth and
      differentiation; disruption of these processes may lead to leukemogenesis. Here
      we attempt to identify functionally novel and partially characterized
      TFs/regulatory proteins that are expressed in undifferentiated hematopoietic
      tissue. We surveyed our database of 15 970 genes/expressed sequence tags (ESTs)
      representing the normal human CD34(+) cells transcriptosome
      (http://westsun.hema.uic.edu/cd34.html), using the UniGene annotation text
      descriptor, to identify genes with motifs consistent with transcriptional
      regulators; 285 genes were identified. We also extracted the human homologues of
      the TFs reported in the murine stem cell database (SCdb;
      http://stemcell.princeton.edu/), selecting an additional 45 genes/ESTs. An
      exhaustive literature search of each of these 330 unique genes was performed to
      determine if any had been previously reported and to obtain additional
      characterizing information. Of the resulting gene list, 106 were considered to be
      potential TFs. Overall, the transcriptional regulator dataset consists of 165
      novel or poorly characterized genes, including 25 that appeared to be TFs. Among
      these novel and poorly characterized genes are a cell growth regulatory with ring
      finger domain protein (CGR19, Hs.59106), an RB-associated CRAB repressor (RBAK,
      Hs.7222), a death-associated transcription factor 1 (DATF1, Hs.155313), and a p38
      interacting protein (P38IP, Hs. 171185). The identification of these novel and
      partially characterized potential transcriptional regulators adds a wealth of
      information to understanding the molecular aspects of hematopoiesis and
      hematopoietic disorders.

PMID- 12070016
TI  - Engraftment potential of human fetal hematopoietic cells in NOD/SCID mice is not
      restricted to mitotically quiescent cells.
AB  - During fetal development, there is a continued demand for large numbers of
      primitive and mature hematopoietic cells. This demand may require that all
      potential hematopoietic stem cells (HSCs) migrate effectively to emerging
      hematopoietic sites and subsequently contribute to blood cell production,
      regardless of their cell cycle status. We recently established that umbilical
      cord blood cells in the G(1) phase of the cell cycle have a repopulating
      potential similar to cells in G(0), suggesting that cycling prenatal and neonatal
      HSCs may have the same functional capabilities described for quiescent, but not
      cycling, cells from adult sources. To establish the relationship between cell
      cycle status and hematopoietic potential at early stages of human ontogeny, the
      in vivo engraftment potential of mitotically defined fetal liver (FL) and fetal
      bone marrow (FBM) cells were examined in NOD/SCID recipients. Following
      transplantation of the same numbers of G(0), G(1), or S/G(2)+M CD34(+) cells from
      FL, equivalent percentages of recipient mice were chimeric (55%, 60%, and 60%,
      respectively). FBM-derived CD34(+) cells in all phases of the cell cycle
      engrafted in conditioned recipients and sustained human hematopoiesis, albeit at
      lower levels than their FL-derived counterparts. Multilineage differentiation was
      evident in all transplanted mice independent of the source or cell cycle status
      of graft cells. In addition, levels of chimerism in mice transplanted with fetal
      blood-derived G(0) or G(1) CD34(+) lineage-depleted cells were similar. These
      results support the assertion that mitotically quiescent and cycling fetal
      hematopoietic cells contain marrow-repopulating stem cells capable of
      multilineage engraftment in NOD/SCID mouse recipients.

PMID- 12070018
TI  - Reconstitution of adhesive properties of human platelets in liposomes carrying
      both recombinant glycoproteins Ia/IIa and Ib alpha under flow conditions:
      specific synergy of receptor-ligand interactions.
AB  - Liposomes carrying both recombinant glycoprotein Ia/IIa (rGPIa/IIa) and Ib alpha
      (rGPIb alpha) (rGPIa/IIa-Ib alpha-liposomes) instantaneously and irreversibly
      adhered to the collagen surface in the presence of soluble von Willebrand factor
      (VWF) at high shear rates, in marked contrast with translocation of liposomes
      carrying rGPIb alpha alone on the VWF surface. In the absence of soluble VWF, the
      adhesion of rGPIa/IIa-Ib alpha-liposomes to the collagen surface decreased with
      increasing shear rates, similar to liposomes carrying rGPIa/IIa alone. While
      adhesion of liposomes with exofacial rGPIa/IIa and rGPIb alpha densities of 2.17
      x 10(3) and 1.00 x 10(4) molecules per particle, respectively, was efficient at
      high shear rates, reduction in rGPIb alpha density to 5.27 x 10(3) molecules per
      particle resulted in decreased adhesion even in the presence of soluble VWF. A
      50% reduction in the exofacial rGPIa/IIa density resulted in a marked decrease in
      the adhesive ability of the liposomes at all shear rates tested. The inhibitory
      effect of antibody against GPIb alpha (GUR83-35) on liposome adhesion was greater
      at higher shear rates. Further, the anti-GPIa antibody (Gi9) inhibited liposome
      adhesion more than GUR83-35 at all shear rates tested. These results suggest that
      the rGPIa/IIa-collagen interaction dominates the adhesion of rGPIa/IIa-Ib alpha
      liposomes to the collagen surface at low shear rates, while the rGPIa/IIa
      collagen and rGPIb alpha-VWF interaction complements each other, and they
      synergistically provide the needed functional integration required for liposome
      adhesion at high shear rates. This study thus has confirmed for the first time
      the proposed mechanisms of platelet adhesion to the collagen surface under flow
      conditions using the liposome system.

PMID- 12070017
TI  - The regulation of platelet-dense granules by Rab27a in the ashen mouse, a model
      of Hermansky-Pudlak and Griscelli syndromes, is granule-specific and dependent on
      genetic background.
AB  - The ashen (ash) mouse, a model for Hermansky-Pudlak syndrome (HPS) and for a
      subset of patients with Griscelli syndrome, presents with hypopigmentation,
      prolonged bleeding times, and platelet storage pool deficiency due to a mutation
      which abrogates expression of the Rab27a protein. Platelets of mice with the
      ashen mutation on the C3H/HeSnJ inbred strain background have greatly reduced
      amounts of dense granule components such as serotonin and adenine nucleotides
      though near-normal numbers of dense granules as enumerated by the dense granule
      specific fluorescent dye mepacrine. Thus, essentially normal numbers of platelet
      dense granules are produced but the granule interiors are abnormal. Collagen
      mediated aggregation of mutant platelets is significantly depressed. No
      abnormalities in the concentrations or secretory rates of 2 other major platelet
      granules, lysosomes and alpha granules, were apparent. Similarly, no platelet
      ultrastructural alterations other than those involving dense granules were
      detected. Therefore, Rab27a regulates the synthesis and secretion of only one
      major platelet organelle, the dense granule. There were likewise no mutant
      effects on levels or secretion of lysosomal enzymes of several other tissues.
      Together with other recent analyses of the ashen mouse, these results suggest a
      close relationship between platelet dense granules, melanosomes of melanocytes
      and secretory lysosomes of cytotoxic T lymphocytes, all mediated by Rab27a.
      Surprisingly, the effects of the ashen mutation on platelet-dense granule
      components, platelet aggregation, and bleeding times were highly dependent on
      genetic background. This suggests that bleeding tendencies may likewise vary
      among patients with Griscelli syndrome and HPS with Rab27a mutations.

PMID- 12070019
TI  - Factor VIII expression in azoxymethane-induced murine fulminant hepatic failure.
AB  - Fulminant hepatic failure (FHF) in humans produces a bleeding diathesis due in
      large part to a reduction in the biosynthesis of liver-derived coagulation
      factors. Remarkably, factor VIII procoagulant activity is elevated in most of
      these patients despite widespread liver cell death. FHF can be modeled in mice by
      administration of azoxymethane, the active ingredient found in cycad palm nuts.
      We compared the expression of factor VIII to other hepatic hemostatic factors in
      azoxymethane-induced murine FHF. Mice displayed dose-dependent decreases in all
      coagulation factor activities measured, including factors V, VII, VIII, and IX.
      At the highest dose of azoxymethane (50 microg/g body weight), factor VIII
      activity in plasma decreased by 98% within 36 hours after treatment, which was
      associated with an 80% reduction in hepatic factor VIII messenger RNA (mRNA). In
      contrast, factor VIII mRNA levels in spleen, kidney, and lung tissue of
      azoxymethane-treated mice were unchanged. Cellular damage in these mice appeared
      to be limited to hepatocytes as evident by histologic examination. This finding
      is supported by 2 observations. First, hepatic mRNA levels of von Willebrand
      factor, which is synthesized by liver sinusoidal endothelial cells but not
      hepatocytes, were unchanged. Second, von Willebrand factor was detected
      antigenically in liver sections of azoxymethane-treated mice by
      immunofluorescence. These results indicate that the contribution of the liver to
      factor VIII biosynthesis is not replaced or significantly supplemented by other
      tissues in this model of FHF.

PMID- 12070020
TI  - Thrombin functions during tissue factor-induced blood coagulation.
AB  - Tissue factor-induced blood coagulation was studied in 20 individuals, for
      varying periods of time during 54 months, in contact pathway-inhibited whole
      blood at 37 degrees C and evaluated in terms of the activation of various
      substrates. After quenching over time with inhibitors, the soluble phases were
      analyzed for thrombin-antithrombin III (TAT) complex formation, prothrombin
      fragments, platelet activation (osteonectin release), factor Va generation,
      fibrinopeptide (FP) A and FPB release, and factor XIII activation. TAT complex
      formation, for 35 experiments, showed an initiation phase (up to 4.6 +/- 0.6
      minutes) in which thrombin was generated at an average rate of 0.93 +/- 0.3
      nM/min catalyzed by about 1.3 pM prothrombinase yielding approximately 26 nM
      thrombin. During a subsequent propagation phase, thrombin was generated at a rate
      of 83.9 +/- 3.8 nM/min by about 120 pM prothrombinase, reaching ultimate levels
      of 851 +/- 53 nM. Clot time, determined subjectively, occurred at 4.7 +/- 0.2
      minutes and correlated with the inception of the propagation phase. The thrombin
      concentrations associated with the transitions to rapid product formation are 510
      +/- 180 pM for platelet activation (1.9 +/- 0.2 minutes), 840 +/- 280 pM for
      factor XIII activation and factor Va generation (2.2 +/- 0.6 minutes), 1.3 +/-
      0.4 nM for FPA release (2.5 +/- 0.7 minutes), 1.7 +/- 0.5 nM for FPB release and
      prethrombin 2 (2.8 +/- 0.8 minutes), 7.0 +/- 2.2 nM for thrombin B chain (3.6 +/-
      0.2 minutes), and 26 +/- 6.2 nM for the propagation phase of TAT formation (4.6
      +/- 0.6 minutes). These results illustrate that the initial activation of
      thrombin substrates occurs during the initiation phase at less than 2 nM thrombin
      (0.2%). Most thrombin (96%) is formed well after clotting occurs.

PMID- 12070021
TI  - Circulating and binding characteristics of wild-type factor IX and certain Gla
      domain mutants in vivo.
AB  - Residue K5 in factor IX gamma-carboxyglutamic acid (Gla) domain participates in
      binding endothelial cells/collagen IV. We injected recombinant factor IX
      containing mutations at residue 5 (K5A, K5R) into factor IX-deficient mice and
      compared their behavior with that of wild-type factor IX. The plasma
      concentration of factor IX that binds to endothelial cells/collagen IV
      (recombinant wild type and K5R) was consistently lower than that of the one that
      does not bind (K5A). Mice treated with wild type or K5R had 79% of the injected
      factor IX in the liver after 2 minutes, whereas 17% remained in circulation. In
      mice injected with K5A, 59% of the injected factor IX was found in liver and 31%
      was found in plasma. When we blocked the liver circulation before factor IX
      injection, 74% of K5A and 64% of K5R remained in the blood. When we treated the
      mouse with EDTA after injecting exogenous factor IX, the blood levels of factor
      IX that bind to endothelial cells/collagen IV increased, presumably because of
      release from endothelial cell/collagen IV binding sites. In contrast, the levels
      of the mutants that do not bind were unaffected by EDTA. In immunohistochemical
      studies, factor IX appears on the endothelial surfaces of mouse arteries after
      factor IX injection and of human arteries from surgical specimens. Thus, we have
      demonstrated that factor IX binds in vivo to endothelial cell-collagen IV
      surfaces. Our results suggest that factor IX Gla-domain mediated binding to
      endothelial cells/collagen IV plays a role in controlling factor IX concentration
      in the blood.

PMID- 12070022
TI  - Paraneoplastic myasthenia gravis correlates with generation of mature naive
      CD4(+) T cells in thymomas.
AB  - Myasthenia gravis (MG) is the leading paraneoplastic manifestation of thymomas
      and is probably related to the capacity of thymomas to mature and export
      potentially autoreactive T cells. Why some thymomas are MG associated (MG+) and
      others are not (MG-) has been unclear. We addressed this question by comparing
      the percentages of intratumorous naive mature CD45RA+ thymocytes in 9 MG(+) and
      in 13 MG(-) thymomas by fluorescence-activated cell sorting analysis. Our results
      show that intratumorous naive CD4 T cells were present in all MG(+) thymomas and
      in one MG(-) thymoma with the development of MG only 2 months after surgery. By
      contrast, the percentage of naive CD4(+) T cells was significantly reduced in all
      13 MG(-) thymomas (P <.0001). Alterations in intratumorous thymopoiesis were
      reflected by corresponding alterations of naive T-cell subset composition in the
      blood, in that only MG(-) patients had significantly decreased levels (P =.02) of
      naive CD4(+) T cells compared with age- and sex-matched control persons. We
      conclude that paraneoplastic MG is highly associated with the efficiency of
      thymomas to produce and export naive CD4(+) T cells. The acquisition of the
      CD45RA(+) phenotype on CD4(+) T cells during terminal intratumorous thymopoiesis
      is associated with the presence of MG in most thymoma patients.

PMID- 12070024
TI  - Antigen-bearing immature dendritic cells induce peptide-specific CD8(+)
      regulatory T cells in vivo in humans.
AB  - Regulatory T cells (T(R)s) can suppress the function of other effector T cells in
      the setting of autoimmunity, transplantation, and resistance to tumors. The
      mechanism for the induction of T(R)s has not been defined. We previously reported
      that an injection of immature dendritic cells (DCs) pulsed with influenza matrix
      peptide (MP) led 7 days later to antigen-specific silencing of effector T-cell
      function in the blood of 2 healthy human subjects. Here, we found that interferon
      gamma-producing effectors return by 6 months. Importantly, in mixing experiments,
      CD8(+) T cells from the sample obtained 7 days after injection could suppress MP
      specific effectors obtained before injection and those in recovery samples. This
      suppression or regulation was specific for the immunizing peptide (MP) and cell
      dose dependent, and it required contact between the 2 samples. These data show
      the capacity of immature DCs to induce antigen-specific regulatory CD8(+) T cells
      in humans.

PMID- 12070023
TI  - T-cell responses against chronic lymphocytic leukemia cells: implications for
      immunotherapy.
AB  - Chronic lymphocytic leukemia (CLL) cells are ineffective antigen-presenting cells
      (APCs) although CD40-activated CLL cells can stimulate proliferation of
      autologous and allogeneic T cells. We examined the antigen-presenting capacity of
      CD40-activated CLL cells as well as dendritic cells pulsed with apoptotic bodies
      of CLL cells to generate autologous and allogeneic immune responses against CLL
      cells. Both APC types were capable of generating T-cell lines that proliferate
      specifically in response to unstimulated CLL cells. Whereas cytotoxic responses
      against stimulated and unstimulated CLL cells could be repeatedly generated by
      allogeneic healthy donors, autologous cytotoxic immune responses against CD40
      activated and native CLL cells were rarely detected. However, T cells isolated
      from patients with CLL could recognize and lyse allogeneic stimulated and
      unstimulated CLL cells, demonstrating that cytotoxic T cells from these tumor
      bearing patients are functionally intact.

PMID- 12070025
TI  - Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and
      paroxysmal nocturnal hemoglobinuria measured by V beta CDR3 spectratyping and
      flow cytometry.
AB  - We have hypothesized that in aplastic anemia (AA) the presence of antigen
      specific T cells is reflected by their contribution to the expansion of a
      particular variable beta chain (V beta) subfamily and also by clonal CDR3
      skewing. To determine the role of disease-specific "signature" T-cell clones in
      AA, we studied preferential V beta usage by flow cytometry and analyzed V beta
      CDR3 regions for the presence of oligoclonality. We first established the
      contribution of each V beta family to the total CD4(+) and CD8(+) lymphocyte
      pool; in AA and paroxysmal nocturnal hemoglobinuria, a seemingly random
      overrepresentation of different V beta families was observed. On average, we
      found expansion in 3 (of 22 examined) V beta families per patient. When the
      contribution of individual V beta families to the effector pool was examined,
      more striking V beta skewing was found. V beta-CDR3 size distribution was
      analyzed for the expanded V beta families in isolated CD4(+) and CD8(+)
      populations; underrepresented V beta families displayed more pronounced CDR3
      skewing. Expanded CD4(+)V beta subfamilies showed mostly a polyclonal CDR3 size
      distribution with only 38% of skewing in expanded V beta families. In contrast,
      within overrepresented CD8(+)V beta types, marked CDR3 skewing (82%) was seen,
      consistent with nonrandom expansion of specific CD8(+) T-cell clones. No
      preferential expansion of particular V beta families was observed, in relation to
      HLA-type. In patients examined after immunosuppressive therapy, an abnormal V
      beta-distribution pattern was retained, but the degree of expansion of individual
      V beta was lower. As V beta skewing may correlate with relative V beta size,
      oligoclonality in combination with numerical V beta expansion can be applied to
      recognition of disease-specific T-cell receptors.

PMID- 12070026
TI  - Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) acts as a regulator
      of B-cell development, B-cell antigen receptor (BCR)-mediated activation, and
      autoimmune disease.
AB  - Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is an immunoglobulin
      immunoreceptor tyrosine-based inhibitory motif (Ig-ITIM) superfamily member that
      recruits and activates protein-tyrosine phosphatases, SHP-1 and SHP-2, through
      its intrinsic ITIMs. PECAM-1-deficient (PECAM-1(-/-) ) mice exhibit a
      hyperresponsive B-cell phenotype, increased numbers of B-1 cells, reduced B-2
      cells, and develop autoantibodies. In the periphery, there are reduced mature
      recirculating B-2 cells and increased B-1a cells within the peritoneal cavity. In
      addition, PECAM-1(-/-) B cells display hyperproliferative responses to
      lipopolysaccharide and anti-IgM stimulation and showed enhanced kinetics in their
      intracellular Ca(++) response following IgM cross-linking. PECAM-1(-/-) mice
      showed increased serum levels of IgM with elevated IgG isotypes and IgA
      antidinitrophenol antibody in response to the T-independent antigen,
      dinitrophenol-Ficoll. Finally, PECAM-1(-/-) mice developed antinuclear antibodies
      and lupuslike autoimmune disease with age.

PMID- 12070028
TI  - Transgenic expression of CD40 ligand produces an in vivo antitumor immune
      response against both CD40(+) and CD40(-) plasmacytoma cells.
AB  - Because tumor-specific antigens have been identified in multiple myeloma (MM),
      immunotherapy might provide an additional treatment modality for the disease.
      Expression of CD40 ligand (CD40L) proximate to the MM cells might serve this
      purpose, either by increasing their capacity to present self-antigens by
      activation through their CD40 receptor or by the recruitment of professional
      antigen-presenting cells (APCs) able to take up and present tumor-associated
      antigens. To distinguish between these possibilities and predict whether human
      CD40(-) myeloma might respond to this approach, we examined 3 murine plasmacytoma
      cell lines, 2 (MPC-11 and S107) expressing the CD40 molecule and 1 (X-24) lacking
      such expression. Syngeneic BALB/CBYJ mice were inoculated subcutaneously with
      tumor cells mixed with CL7.1 fibroblasts, retrovirally transduced to express
      either the mCD40L or the neo gene. For all 3 plasmacytoma cell lines, coinjection
      with CL7.1/mCD40L significantly reduced local tumor growth compared with
      controls. This effect was mediated by a systemic antitumor immune response, since
      mice immunized with tumor and CL7.1/mCD40L were resistant to subsequent challenge
      with tumor, and tumor growth inhibition was abolished when CD8(+) or CD4(+)
      lymphocytes were depleted. Because expression of CD40L gave equivalent protection
      from CD40(+) and CD40(-) tumors and transgenic-CD40L failed to up-regulate
      costimulatory molecules in either tumor, the protective effects of CD40L probably
      resulted from recruitment/activation of professional APCs rather than from CD40
      activation of plasmacytoma cells. As further support of this concept, we found
      that mice were also well protected if CL7.1 and CD40L were injected together with
      apoptotic plasmacytoma cells from these tumors. Hence, transgenic CD40L
      expression may produce an antimyeloma immune response against either CD40(+) or
      CD40(-) tumors and may be of therapeutic value for both types of myeloma in
      humans.

PMID- 12070027
TI  - Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential
      survival protein of human myeloma cells.
AB  - Multiple myeloma (MM) is a plasma cell malignancy that occurs mainly in bone
      marrow. As MM cells proliferate slowly, it would seem essential to find means of
      preventing their growth and accumulation inside bone marrow. The present study
      used an antisense strategy to elucidate the respective roles of Bcl-2, Bcl-x(L),
      and Mcl-1 proteins in myeloma cell survival. Each antisense oligonucleotide (ASO;
      Bcl-2, Bcl-x(L), or Mcl-1 ASO) introduced into human myeloma cell lines by
      electroporation induced a marked reduction in the level of the corresponding
      protein. Mcl-1 ASO triggers an important decrease of viability in all myeloma
      cell lines tested and in 2 primary myeloma cells, whereas neither Bcl-2 nor Bcl
      x(L) ASO affected the viability of myeloma cells. The decrease of cell viability
      induced by Mcl-1 ASO treatment was associated with an induction of apoptosis that
      occurred through the disruption of mitochondrial membrane potential Delta Psi m
      and the activation of executioner caspase-3. Furthermore, we have shown that
      interleukin 6 cannot prevent the Mcl-1 ASO-induced apoptosis. Finally, although
      Bcl-2 ASO treatment alone has no effect, it can sensitize myeloma cell lines to
      dexamethasone (Dex), whereas Bcl-x(L) ASO in combination with Dex still had no
      effect. As MM remains an incurable disease despite intensive chemotherapy, these
      results suggest that Mcl-1 antisense strategy rather than Bcl-2 antisense
      strategy could be of considerable importance in the treatment of MM.

PMID- 12070029
TI  - Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with
      the alpha-emitting radionuclide, bismuth 213.
AB  - We used a pretargeting technique to treat a nonobese diabetic/severe combined
      immunodeficient murine model of human adult T-cell leukemia with an anti-Tac
      antibody-streptavidin (HAT-SA) conjugate, which recognizes CD25, followed by
      bismuth 213 ((213)Bi)-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid
      (DOTA)- biotin. In the 3-step pretargeting radioimmunotherapy protocol, HAT-SA
      (140 or 400 microg) was administered intravenously (i.v.) to bind to the
      interleukin 2 receptor alpha (IL-2R alpha; CD25)-expressing tumor cells. After 24
      hours, 100 microg of a synthetic clearing agent was administered i.v. to remove
      unbound circulating HAT-SA conjugate from the circulation. Four hours later,
      (213)Bi-DOTA-biotin was administered i.v. for therapy. Tumor growth was
      significantly inhibited in 3 trials by using 250 microCi (9.25 MBq) of (213)Bi
      DOTA-biotin with a pretargeting technique as monitored by serum levels of soluble
      IL-2R alpha and/or human beta-2-microglobulin (P <.05, t test) and by survival of
      tumor-bearing mice in the treatment groups (P <.02, log rank test) as compared
      with the control groups. No prolongation of survival was observed with a
      nonspecific antibody-SA conjugate or in the absence of the radionuclide.
      Additionally, no prolongation of survival resulted from administration of (213)Bi
      directly linked to intact HAT. Furthermore, there was no prolongation of survival
      when the beta-emitting radionuclide yttrium 90 instead of the alpha-emitting
      radionuclide (213)Bi was used. The pretargeting approach with (213)Bi inhibited
      tumor growth more effectively than did immunotherapy with unmodified HAT. The
      best results were obtained with combination therapy that involved (213)Bi-DOTA
      biotin with a pretargeting technique supplemented by 4 weekly doses of HAT. The
      findings of this study support the use of this combination approach in a clinical
      trial in patients with IL-2R alpha-expressing leukemias.

PMID- 12070030
TI  - Activation-induced cell death of aggressive histology lymphomas by CD40
      stimulation: induction of bax.
AB  - CD40 is present on both normal and neoplastic B-lineage cells. CD40 stimulation
      of normal B cells has been shown to promote normal growth and differentiation,
      whereas aggressive histology B lymphomas are growth inhibited. The inhibition of
      neoplastic B-cell growth is believed to occur via activation-induced cell death
      in which stimuli that typically promote the growth of normal cells prevent the
      growth of their neoplastic counterparts. We show here that CD40 stimulation using
      either a soluble recombinant human CD40 ligand (srhCD40L) or anti-CD40 monoclonal
      antibody resulted in apoptosis of human Burkitt lymphoma cell lines. Additional
      studies examining the mechanism of CD40-mediated death revealed an increase in
      bax messenger RNA with a subsequent increase in Bax protein in the mitochondria
      of the treated cells. In vitro exposure of the cells to bax antisense
      oligonucleotides resulted in a significant decline in Bax protein levels and
      partial protection from CD40-mediated death, indicating that induction of Bax was
      at least one mechanism underlying this inhibitory effect of CD40 stimulation on
      lymphomas. When immunodeficient mice bearing Burkitt lymphoma were treated with
      srhCD40L, significant increases in survival were observed indicating a direct
      antitumor effect as a result of CD40 stimulation in vivo. Overall, these results
      demonstrate that CD40 ligation of aggressive histology B-lymphoma cells results
      in inhibition both in vitro and in vivo and thus may be of potential clinical use
      in their treatment.

PMID- 12070031
TI  - Repair of DNA interstrand crosslinks as a mechanism of clinical resistance to
      melphalan in multiple myeloma.
AB  - Melphalan is widely used as a preparative agent in patients with multiple myeloma
      (MM) undergoing autologous stem cell transplantation (SCT). Although disease
      relapse is the major cause of death after a melphalan-conditioned autograft, the
      mechanism remains unclear. Melphalan produces a number of DNA adducts with the
      DNA interstrand crosslink (ICL) considered to be the critical cytotoxic lesion.
      By using a modification of the single-cell gel electrophoresis (Comet) assay, we
      have measured formation and repair of DNA ICL in plasma cells from melphalan-
      naive and melphalan-treated patients (ie, those who have relapsed after a
      melphalan-conditioned autologous SCT or oral melphalan therapy). Similar levels
      of dose-dependent DNA interstand crosslinking were observed in cells from both
      melphalan-naive and -treated patients. However, marked differences in ICL repair
      were observed: cells from naive patients showed no repair, whereas those from
      treated patients exhibited between 42% and 100% repair at 40 hours. In vitro
      sensitivity to melphalan in plasma cells was found to correlate with ICL repair.
      These findings suggest that ICL repair may be an important mechanism by which
      melphalan resistance emerges after autologous SCT or oral therapy. This mechanism
      may have implications for MM patients undergoing melphalan therapy.

PMID- 12070032
TI  - Dendritic cells are functionally defective in multiple myeloma: the role of
      interleukin-6.
AB  - We studied concentration, phenotype, and function of peripheral blood (PB)
      dendritic cells (DCs) from patients with multiple myeloma (MM). The absolute
      number of circulating precursors of myeloid and plasmacytoid DCs was
      significantly lower in MM patients than in healthy subjects. After maturation,
      PBDCs from MM patients showed significantly lower expression of HLA-DR, CD40, and
      CD80 antigens and impaired induction of allogeneic T-cell proliferation compared
      with controls. Remarkably, they were not capable of presenting the patient
      specific tumor idiotype to autologous T cells. Conversely, DCs generated in vitro
      from CD14(+) monocytes from the same patients, and PBDCs freshly isolated from
      healthy donors efficiently stimulated allogeneic and autologous T cells. To
      clarify the mechanism of PBDC deficiency in MM, we investigated the effects of
      the main plasma cell growth factor, interleukin-6 (IL-6), on the development of
      DCs from CD34(+) cells. IL-6 inhibited the colony growth of CD34(+) DC
      progenitors and switched the commitment of CD34(+) cells from DCs to CD14(+)
      CD1a(-) CD86(-)CD80(-) CD40(+/-)HLA-DR +/- monocytic cells exerting potent
      phagocytic activity but no antigen-presentation capacity. This effect was
      reversed by anti-IL-6 antibodies. Growing CD34(+) cells in the presence of
      autologous serum (without IL-6) also suppressed the development of functional
      DCs. This study demonstrates that PBDCs from MM patients are functionally
      defective, partially because of IL-6-mediated inhibition of development. This
      brings into question the advisability of using PBDCs as antigen carriers for
      immunotherapy trials in MM. The results also suggest a novel mechanism whereby
      myeloma cells escape immune recognition.

PMID- 12070033
TI  - Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in
      mice.
AB  - The hematopathology subcommittee of the Mouse Models of Human Cancers Consortium
      recognized the need for a classification of murine hematopoietic neoplasms that
      would allow investigators to diagnose lesions as well-defined entities according
      to accepted criteria. Pathologists and investigators worked cooperatively to
      develop proposals for the classification of lymphoid and nonlymphoid
      hematopoietic neoplasms. It is proposed here that nonlymphoid hematopoietic
      neoplasms of mice be classified in 4 broad categories: nonlymphoid leukemias,
      nonlymphoid hematopoietic sarcomas, myeloid dysplasias, and myeloid
      proliferations (nonreactive). Criteria for diagnosis and subclassification of
      these lesions include peripheral blood findings, cytologic features of
      hematopoietic tissues, histopathology, immunophenotyping, genetic features, and
      clinical course. Differences between murine and human lesions are reflected in
      the terminology and methods used for classification. This classification will be
      of particular value to investigators seeking to develop, use, and communicate
      about mouse models of human hematopoietic neoplasms.

PMID- 12070034
TI  - Bethesda proposals for classification of lymphoid neoplasms in mice.
AB  - A consensus system for classification of mouse lymphoid neoplasms according to
      their histopathologic and genetic features has been an elusive target for
      investigators involved in understanding the pathogenesis of spontaneous cancers
      or modeling human hematopoietic diseases in mice. An international panel of
      scientists with expertise in mouse and human hematopathology joined with the
      hematopathology subcommittee of the Mouse Models for Human Cancers Consortium to
      develop criteria for definition and classification of these diseases together
      with a standardized nomenclature. The fundamental elements contributing to the
      scheme are clinical features, morphology, immunophenotype, and genetic
      characteristics. The resulting classification has numerous parallels to the World
      Health Organization classification of human lymphoid tumors while recognizing
      differences that may be species specific. The classification should facilitate
      communications about mouse models of human lymphoid diseases.

PMID- 12070035
TI  - Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic
      stem cell pool in myelodysplastic syndromes with trisomy 8.
AB  - Clonality studies of mature cells suggest that the primary transformation event
      in myelodysplastic syndrome (MDS) most frequently occurs in a myeloid-restricted
      progenitor, a hypothesis supported by recent studies of purified CD34(+)Thy1(+)
      hematopoietic stem cells (HSCs) in cases with trisomy 8 (+8). In contrast, we
      recently demonstrated that a lymphomyeloid HSC is the target for transformation
      in MDS cases with del(5q), potentially reflecting heterogeneity within MDS.
      However, since +8 is known to frequently be a late event in the MDS
      transformation process, it remained a possibility that CD34(+)CD38(-)Thy1(+) HSC
      disomic for chromosome 8 might be part of the MDS clone. In the present studies,
      although a variable fraction of CD34(+)CD38(-)Thy1(+) cells were disomic for
      chromosome 8, they did not possess normal HSC activity in long-term cultures and
      nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice. Mixing
      experiments with normal CD34(+)CD38(-) cells suggested that this HSC deficiency
      was intrinsic and not mediated by indirect mechanisms. Furthermore, investigation
      of 4 MDS cases with combined del(5q) and +8 demonstrated that the +8 aberration
      was always secondary to del(5q). Whereas del(5q) invariably occurs in
      CD34(+)CD38(-)Thy-1(+) HSCs, the secondary +8 event might frequently arise in
      progeny of MDS HSCs. Thus, CD34(+)CD38(-)Thy1(+) HSCs are invariably part of the
      MDS clone also in +8 patients, and little HSC activity can be recovered from the
      CD34(+) CD38(-)Thy1(+) HSC. Finally, in advanced cases of MDS, the MDS
      reconstituting activity is exclusively derived from the minor CD34(+)CD38(-) HSC
      population, demonstrating that MDS stem cells have a similar phenotype as normal
      HSCs, potentially complicating the development of autologous transplantation for
      MDS.

PMID- 12070037
TI  - Band 3 is an anchor protein and a target for SHP-2 tyrosine phosphatase in human
      erythrocytes.
AB  - Tyr phosphorylation of the multifunctional transmembrane protein band 3 has been
      implicated in several erythrocyte functions and disorders. We previously
      demonstrated that pervanadate treatment of human erythrocytes induces band-3 Tyr
      phosphorylation, which is catalyzed by the sequential action of tyrosine kinase
      Syk and tyrosine kinase(s) belonging to the Src family. In this study, we show
      that Tyr phosphorylation of band 3, elicited by pervanadate, N-ethylmaleimide, or
      diamide, greatly increases band-3 interaction with the tyrosine phosphatase SHP-2
      in parallel with the translocation of SHP-2 to erythrocyte membranes. These
      events seem to be mediated by Src-like catalyzed phosphorylation of band 3
      because both SHP-2 translocation to cellular membranes and its interaction with
      Tyr-phosphorylated protein are greatly counteracted by PP2, a specific inhibitor
      of Src kinases. Binding-competition experiments demonstrate that SHP-2
      recruitment to band 3 occurs via its SH2 domain(s). In particular, our data
      support the view that SHP-2 docks specifically with P-Y359 of band 3. Experiments
      performed with intact erythrocytes in the presence of the SHP-2 inhibitor
      calpeptin suggest that, once recruited to Tyr-phosphorylated band 3, the tyrosine
      phosphatase dephosphorylates the protein. P-Y8, 21, and 904 are the residues
      affected by SHP-2, as judged by (32)P-peptide mapping of band 3 digested with
      trypsin. These results indicate that in treated erythrocytes, recruitment of
      cytosolic SHP-2 to band 3 is a prerequisite for the subsequent dephosphorylation
      of the transmembrane protein.

PMID- 12070036
TI  - Expression and subcellular localization of NRAMP1 in human neutrophil granules.
AB  - Mutations at the Nramp1 gene cause susceptibility to infections with
      intracellular pathogens. In human blood, polymorphonuclear (PMN) leukocytes are
      the most abundant site of NRAMP1 messenger RNA (mRNA) expression, suggesting that
      NRAMP1 plays an important role in the activity of these cells. By Northern blot
      analysis, NRAMP1 mRNA was only detected in most mature neutrophils from bone
      marrow (band and segmented cells). A high-affinity polyclonal rabbit antihuman
      NRAMP1 antibody directed against the amino terminus of the protein was produced
      and used to study cellular and subcellular localization of the protein in primary
      human neutrophils. Subcellular fractionation of granule populations together with
      immunoblotting studies with granule-specific markers indicate that NRAMP1
      expression is primarily in tertiary granules. These granules are positive for the
      matrix enzyme gelatinase and the membrane subunit of the vacuolar H(+)/ATPase and
      can be recruited for exocytosis by treatment of neutrophils with phorbol
      myristate acetate. Immunogold studies by cryoelectron microscopy with primary
      neutrophils confirm that a majority (75%) of NRAMP1-positive granules are also
      positive for gelatinase, but they also suggest further heterogeneity in this
      granule population. Presence of NRAMP1 in tertiary granules is in agreement with
      the late-stage appearance of NRAMP1 mRNA during neutrophil maturation in bone
      marrow. Finally, immunofluorescence studies of Candida albicans-containing
      phagosomes formed in neutrophils indicate that NRAMP1 is recruited from tertiary
      granules to the phagosomal membrane on phagocytosis, supporting a role for NRAMP1
      in the antimicrobial defenses of human neutrophils.

PMID- 12070038
TI  - Nuclear magnetic resonance studies of mutations at the tetramerization region of
      human alpha spectrin.
AB  - Many spectrin mutations that destabilize tetramer formation and lead to
      hereditary hemolytic anemias are located at the N-terminal region of alpha
      spectrin, with the Arg28 position considered to be a mutation hot spot. We have
      introduced mutations at positions 28 and 45 into a model peptide, Sp alpha 1-156,
      consisting of the first 156 residues in the N-terminal region of alpha-spectrin
      (alpha N). The association of these alpha-spectrin peptides that have single
      amino acid replacements with a beta-spectrin model peptide, consisting of the C
      terminal region of beta-spectrin (beta C), was determined, and structural changes
      due to amino acid replacements were monitored by nuclear magnetic resonance
      (NMR). We found evidence for similar and very localized structural changes in Sp
      alpha 1-156Arg45Thr and Sp alpha 1-156Arg45Ser, although these 2 mutant peptides
      associated with beta-spectrin peptide with significantly differing affinities.
      The Sp alpha 1-156Arg28Ser peptide showed an affinity for the beta-spectrin
      peptide comparable to that of Sp alpha 1-156Arg45Ser, but it exhibited
      substantial and widespread spectral changes. Our results suggest that both Arg45
      replacements induce only minor structural perturbations in the first helix of Sp
      alpha 1-156, but the Arg28Ser replacement affects both the first helix and the
      following structural domain. Our results also indicate that the mechanism for
      reduced spectrin tetramerization is through mutation-induced changes in molecular
      recognition at the alpha beta-tetramerization site, rather than through
      conformational disruption, as has been suggested in prior literature.

PMID- 12070040
TI  - Intersubunit circular permutation of human hemoglobin.
AB  - For many years, human hemoglobin (Hb) isolated from erythrocytes has been
      investigated as a potential oxygen delivery therapeutic. Advantages with respect
      to the need for blood typing were balanced with various undesirable properties of
      cell-free Hb, including cost, overall oxygen affinity, alterations in
      cooperativity, and ready dissociation into toxic dimeric species. The use of
      total gene synthesis has resulted in very high levels of functional human Hb
      expression in Escherichia coli, but there remains a desire for effecting the
      crosslinking of the hemoglobin tetramer and providing for ready means for
      increasing the globular molecular weight. In this communication, we report a
      novel method for linking alpha chains. By circularly permuting one alpha
      sequence, the second alpha chain in the Hb tetramer can be linked with glycine
      residues to form 2 bridges across the central cavity. The second alpha chain thus
      presents its amino and carboxyl termini on a solvent exposed surface, providing
      for additional polymerization of oxygen-carrying subunits or attachment of any
      other peptide-based therapeutic.

PMID- 12070039
TI  - Transferrin receptor hyperexpression in primary erythroblasts is lost on
      transformation by avian erythroblastosis virus.
AB  - In primary chicken erythroblasts (stem cell factor [SCF] erythroblasts),
      transferrin receptor (TfR) messenger RNA (mRNA) and protein were hyperexpressed
      as compared to nonerythroid chicken cell types. This erythroid-specific
      hyperexpression was abolished in transformed erythroblasts (HD3E22 cells)
      expressing the v-ErbA and v-ErbB oncogenes of avian erythroblastosis virus. TfR
      expression in HD3E22 cells could be modulated by changes in exogenous iron
      supply, whereas expression in SCF erythroblasts was not subject to iron
      regulation. Measurements of TfR mRNA half-life indicated that hyperexpression in
      SCF erythroblasts was due to a massive stabilization of transcripts even in the
      presence of high iron levels. Changes in mRNA binding activity of iron regulatory
      protein 1 (IRP1), the primary regulator of TfR mRNA stability in these cells,
      correlated well with TfR mRNA expression; IRP1 activity in HD3E22 cells and other
      nonerythroid cell types tested was iron dependent, whereas IRP1 activity in
      primary SCF erythroblasts could not be modulated by iron administration. Analysis
      of avian erythroblasts expressing v-ErbA alone indicated that v-ErbA was
      responsible for these transformation-specific alterations in the regulation of
      iron metabolism. In SCF erythroblasts high amounts of TfR were detected on the
      plasma membrane, but a large fraction was also located in early and late
      endosomal compartments, potentially concealing temporary iron stores from the IRP
      regulatory system. In contrast, TfR was almost exclusively located to the plasma
      membrane in HD3E22 cells. In summary, stabilization of TfR mRNA and
      redistribution of Fe-Tf/TfR complexes to late endosomal compartments may
      contribute to TfR hyperexpression in primary erythroblasts, effects that are lost
      on leukemic transformation.

PMID- 12070041
TI  - The DAU allele cluster of the RHD gene.
AB  - Variant D occurs frequently in Africans. However, considerably less RHD alleles
      have been described in this population compared with Europeans. We characterized
      5 new RHD alleles, dubbed DAU-0 to DAU-4, that shared a T379M substitution and
      occurred in a cDe haplotype. DAU-1 to DAU-4 were detected in Africans with
      partial D phenotypes. They harbored one and 2 additional missense mutations,
      respectively, dispersed throughout the RhD protein. An anti-D immunization was
      found in DAU-3. DAU-0 carrying T379M only was detected by screening European
      blood donors and expressed a normal D phenotype. Within the phylogeny of the RHD
      alleles, DAU formed an independent allele cluster, separate from the DIVa, weak D
      type 4, and Eurasian D clusters. The characterization of the RH phylogeny
      provided a framework for future studies on RH alleles. The identification of the
      DAU alleles increased the number of known partial D alleles in Africans
      considerably. DAU alleles may be a major cause of antigen D variability and anti
      D immunization in patients of African descent.

PMID- 12070043
TI  - Bismuth 213-labeled anti-CD45 radioimmunoconjugate to condition dogs for
      nonmyeloablative allogeneic marrow grafts.
AB  - To lower treatment-related mortality and toxicity of conventional marrow
      transplantation, a nonmyeloablative regimen using 200 cGy total-body irradiation
      (TBI) and mycophenolate mofetil (MMF) combined with cyclosporine (CSP) for
      postgrafting immunosuppression was developed. To circumvent possible toxic
      effects of external-beam gamma irradiation, strategies for targeted radiation
      therapy were investigated. We tested whether the short-lived (half-life, 46
      minutes) alpha-emitter bismuth 213 ((213)Bi) conjugated to an anti-CD45
      monoclonal antibody (mAb) could replace 200 cGy TBI and selectively target
      hematopoietic tissues in a canine model of nonmyeloablative DLA-identical marrow
      transplantation. Biodistribution studies using iodine 123-labeled anti-CD45 mAb
      showed uptake in blood, marrow, lymph nodes, spleen, and liver. In a dose
      escalation study, 7 dogs treated with the (213)Bi-anti-CD45 conjugate ((213)Bi
      dose, 0.1-5.9 mCi/kg [3.7-218 MBq/kg]) without marrow grafts had no toxic effects
      other than a mild, reversible suppression of blood counts. On the basis of these
      studies, 3 dogs were treated with 0.5 mg/kg (213)Bi-labeled anti-CD45 mAb
      ((213)Bi doses, 3.6, 4.6, and 8.8 mCi/kg [133, 170, and 326 MBq/kg]) given in 6
      injections 3 and 2 days before grafting of marrow from DLA-identical littermates.
      The dogs also received MMF (10 mg/kg subcutaneously twice daily the day of
      transplantation until day 27 afterward) and CSP (15 mg/kg orally twice daily the
      day before transplantation until 35 days afterward). The therapy was well
      tolerated except for transient elevations in levels of transaminases in 3 dogs,
      followed by, in one dog, ascites. All dogs had prompt engraftment and achieved
      stable mixed hematopoietic chimerism, with donor contributions ranging from 30%
      to 70% after more than 27 weeks of follow-up. These results will form the basis
      for additional studies in animals and later the design of clinical trials using
      (213)Bi as a nonmyeloablative conditioning regimen with minimal toxicity.

PMID- 12070042
TI  - Growth factor treatment prior to low-dose total body irradiation increases donor
      cell engraftment after bone marrow transplantation in mice.
AB  - Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are
      widely explored. We developed a new protocol using hematopoietic growth factors
      prior to low-dose total body irradiation (TBI) in recipients of autologous
      transplants to establish high levels of long-term donor cell engraftment. We
      hypothesized that treatment of recipient mice with growth factors would
      selectively deplete stem cells, resulting in successful long-term donor cell
      engraftment after transplantation. Recipient mice were treated for 1 or 7 days
      with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus
      Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low
      dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of
      congenic bone marrow cells. High levels of donor cell engraftment were observed
      in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although
      1-day pretreatments with these cytokines initially resulted in reduced donor cell
      engraftment, a continuous increase in time was observed, finally resulting in
      highly significantly increased levels of donor cell contribution. In contrast, G
      CSF treatment showed no beneficial effects on long-term engraftment. In vitro
      stem cell assays demonstrated the effect of cytokine treatment on stem cell
      numbers. Donor cell engraftment and number of remaining recipient stem cells
      after TBI were strongly inversely correlated, except for groups treated for 1 day
      with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell
      engraftment can be strongly augmented by treatment of recipient mice prior to low
      dose TBI with hematopoietic growth factors that act on primitive cells.

PMID- 12070044
TI  - Enhancement of G-CSF-induced stem cell mobilization by antibodies against the
      beta 2 integrins LFA-1 and Mac-1.
AB  - The beta 2 integrins leukocyte function antigen-1 (LFA-1, CD11a) and macrophage
      antigen-1 (Mac-1, CD11b) have been reported to play a role in the attachment of
      CD34(+) cells to stromal cells in the bone marrow. When administered prior to
      interleukin-8 (IL-8), anti-LFA-1 antibodies completely prevent the IL-8-induced
      mobilization of hematopoietic stem cells in mice. Here, we studied the role of
      anti-beta 2 integrin antibodies in granulocyte colony-stimulating factor (G-CSF)
      induced mobilization of hematopoietic progenitor cells. Administration of
      antibodies against the alpha chain of LFA-1 or against the alpha chain of Mac-1
      followed by daily injections of G-CSF for more than 1 day resulted in a
      significant enhancement of mobilization of hematopoietic progenitor cells when
      compared with mobilization induced by G-CSF alone. Also, the number of late (day
      28) cobblestone area-forming cells in vitro was significantly higher after
      mobilization with anti-LFA-1 antibodies followed by 5 microg G-CSF for 5 days
      than with G-CSF alone (119 +/- 34 days vs 17 +/- 14 days), indicating
      mobilization of repopulating stem cells. Pretreatment with blocking antibodies to
      intercellular adhesion molecule-1 (ICAM-1; CD54), a ligand of LFA-1 and Mac-1,
      did not result in an effect on G-CSF-induced mobilization, suggesting that the
      enhancing effect required an interaction of the beta 2 integrins and one of their
      other ligands. Enhancement of mobilization was not observed in LFA-1-deficient
      (CD11a) mice, indicating that activated cells expressing LFA-1 mediate the
      synergistic effect, rather than LFA-1-mediated adhesion.

PMID- 12070045
TI  - Fludarabine induces apoptosis, activation, and allogenicity in human endothelial
      and epithelial cells: protective effect of defibrotide.
AB  - Fludarabine is a nonmyeloablative immunosuppressant increasingly used as a
      component of alternative conditioning regimens before allogeneic bone marrow
      transplantation. It is expected to reduce conditioning-related toxicity and
      proinflammatory activation of the host tissues. However, in our in vitro study,
      we provide evidence that 2-fluoroadenine 9-beta-D-arabinofuranoside (F-Ara) as
      the active metabolized form of fludarabine damages human microvascular
      endothelial cells (HMECs) and dermal and alveolar epithelial cell lines after 48
      hours of culture when it is used in pharmacologically relevant concentrations
      (range, 10 microg/mL-1 microg/mL). In addition, flow cytometric analyses revealed
      a significant up-regulation of intercellular adhesion molecule 1 and major
      histocompatibility complex (MHC) class I molecules by F-Ara, suggesting a
      proinflammatory activation of HMECs. Cytotoxicity assays demonstrated that target
      HMECs pretreated with F-Ara (10 microg/mL) showed increased lysis by allogeneic
      MHC class I-restricted cytotoxic T lymphocytes from healthy human donors. We
      conclude that, beside its immunosuppressive activities, F-Ara can be harmful for
      target tissues of transplantation-related complications and can even stimulate
      allogeneic immune responses. We identified the pharmaceutical compound
      defibrotide as protective against F-Ara- induced apoptosis and alloactivation,
      importantly, without affecting the antileukemic effect of F-Ara. This observation
      argues for a potential clinical usage of defibrotide in pretransplantation
      conditioning.

PMID- 12070046
TI  - Activated platelets of patients with paroxysmal nocturnal hemoglobinuria express
      cellular prion protein.
AB  - Cellular prion protein (PrPc) is a glycosylphosphatidylinositol (GPI)-anchored
      membrane glycoprotein that contains a putative membrane-spanning section.
      Patients with paroxysmal nocturnal hemoglobinuria (PNH) lack GPI proteins on the
      surface of somatically mutated hematopoietic stem cell and its progeny. Platelet
      expression of PrPc was studied in 8 PNH patients. Resting PNH (CD55(-)) platelets
      were devoid of surface PrPc, but activation of platelets resulted in the surface
      expression of PrPc. Expressed PrPc was detected by 2 monoclonal antibodies (mAbs)
      against the N-terminal part of the molecule but not by mAb 6H4, which binds at
      the C-terminus beyond the membrane-spanning section. However, 6H4 detected PrPc
      on Western blots of PNH platelets, demonstrating that the lack of 6H4 binding was
      not caused by PrPc truncation. Our results indicate that in the absence of GPI
      anchor, PrPc can be expressed intracellularly and up-regulated on the platelet
      membrane, likely in a transmembrane form with the C-terminal part of the molecule
      inserted into the cytoplasm.

PMID- 12070047
TI  - Glycoprotein V: the predominant target antigen in gold-induced autoimmune
      thrombocytopenia.
AB  - Autoimmune thrombocytopenia is generally caused by autoantibodies against
      glycoprotein (GP) IIb-IIIa or GPIb-IX and occasionally against GPIa-IIa or GPV.
      By investigating 38 rheumatoid arthritis (RA) patients on gold therapy, 10 with
      profound thrombocytopenia and 28 nonthrombocytopenic controls, we showed that in
      all 10 patients with thrombocytopenia, the platelet autoantibodies preferentially
      targeted GPV but the presence of gold was not required for their reactivity.
      Elevated levels of platelet-associated IgG (PAIgG) were observed in 8 of the 10
      patients in whom the tests were performed. In 5 patients with sufficient
      autologous platelets, the GPV specificity of PAIgG was confirmed. Tests with GPV
      transfectants revealed that the antibodies reacted with GPV independent of GPIb
      alpha, GPIb beta, or GPIX. Autoantibodies recognizing GPV were not seen in the 28
      nonthrombocytopenic control RA patients. Thus, GPV seems to be targeted in gold
      induced autoimmune thrombocytopenia.

PMID- 12070048
TI  - Nondisjunction of chromosomes leading to hyperdiploid childhood B-cell precursor
      acute lymphoblastic leukemia is an early event during leukemogenesis.
AB  - A hyperdiploid karyotype is found in 30% of B-cell precursor acute lymphoblastic
      leukemias in childhood. The time of nondisjunction of chromosomes leading to
      hyperdiploidy during leukemogenesis is unknown. We used the 3 clonotypic
      immunoglobulin heavy chain (IgH) gene rearrangements as molecular markers for
      each of the 3 chromosomes 14 in a case with hyperdiploid acute lymphoblastic
      leukemia to define the order of events-namely, somatic recombination and
      nondisjunction of chromosomes-during leukemia development. A partial sequence
      homology of the incomplete DJ(H) rearrangement with 1 of the 2 nonfunctional
      VDJ(H) rearrangements suggests that the doubling of chromosomes had occurred
      after this DJ(H) rearrangement and thus during early B-cell differentiation. The
      occurrence of the nondisjunction of chromosomes as well as ongoing rearrangement
      processes in utero were confirmed by the presence of all 3 IgH rearrangements in
      neonatal blood spots, providing the first evidence that hyperdiploidy formation
      is an early event in leukemogenesis in these leukemias.

PMID- 12070049
TI  - Role of GITR in activation response of T lymphocytes.
AB  - In this study, we describe the generation and characterization of mice in which
      GITR gene (TNFRSF18 [tumor necrosis factor receptor superfamily 18]), a member of
      the TNFRSF expressed mainly on T lymphocytes, has been ablated (GITR(-/-) mice).
      Results indicate that GITR inactivation does not impair the normal development of
      the lymphoid organs but modulates T-cell activation. In fact, when GITR(-/-) T
      lymphocytes are activated by treatment with an anti-CD3 monoclonal antibody they
      proliferate more than wild-type cells. Moreover, activated GITR(-/-) T
      lymphocytes express higher levels of interleukin-2 receptor, produce larger
      amounts of interleukin-2, and are more sensitive to activation-induced cell death
      than controls. These results suggest that GITR is involved in the regulation of T
      cell receptor/CD3-driven T-cell activation and programmed cell death.

PMID- 12070051
TI  - Hydrops fetalis-associated congenital dyserythropoietic anemia treated with
      intrauterine transfusions and bone marrow transplantation.
AB  - Hydrops fetalis is rarely caused by congenital dyserythropoietic anemia (CDA). We
      report a patient with hydrops fetalis as a result of severe anemia. This patient
      needed intrauterine transfusions from 21 weeks of gestation until birth. The
      hematologic study showed an atypical CDA (hydrops fetalis-associated CDA)
      characterized by features resembling CDA type II, but negative acidified serum
      lysis test (HEMPAS negative). The patient was regularly transfused for a year,
      after which an allogeneic bone marrow transplantation (BMT) from an HLA-identical
      sibling was successfully carried out. His actual hemoglobin is 127 g/L, and he
      has not received transfusions for more than a year. In conclusion, intrauterine
      transfusions and BMT could cure an otherwise lethal atypical CDA.

PMID- 12070050
TI  - Influence of plasma immunoglobulin level on antibody synthesis.
AB  - In previous experimental animal studies it has been demonstrated that antibody
      depletion is not followed by increased antibody synthesis. To assess whether
      these results are conferrable to antibody-depleted humans, we measured free light
      chains (flcs) as markers of current antibody synthesis in 8 patients treated with
      immunoadsorption (IA) therapy. Specific and bulk immunoglobulin levels were
      obtained simultaneously. The mean serum flc concentration increased to the
      preapheresis value within 1 day and remained unchanged thereafter. Total
      immunoglobulin G (IgG) and specific antibody concentrations increased to
      pretreatment values in 88% and 43% of the patients, respectively, and remained
      below the original values in the others. In conclusion, the lack of increased flc
      synthesis after IA confirms the absence of a feedback mechanism regulating
      antibody synthesis. The restoration of serum IgG levels after IA, therefore, does
      not result from increased antibody synthesis but is probably related to changes
      of catabolism and immunoglobulin backflow.

PMID- 12070052
TI  - The G20210A mutation does not affect the stability of prothrombin mRNA in vivo.
AB  - The activated form of prothrombin plays pivotal roles in the regulation of
      crucial coagulation, fibrinolytic, and cellular processes. Among several
      congenital genetic defects affecting the prothrombin gene, a G-->A mutation at
      position 20210--the accepted polyadenylation site--has been linked to
      hyperprothrombinemia and a corresponding increase in venous and arterial
      thrombotic risk. The current study substantiates the hypothesis that the 20210A
      mutation effects posttranscriptional dysregulation of the prothrombin messenger
      RNA (mRNA). Moreover, data from experiments carried out in fresh liver tissue
      indicate that the 20210A mutation does not affect prothrombin mRNA stability but,
      rather, effects a change in the location of the 3'-cleavage/polyadenylation
      reaction. Based upon this evidence, we propose an alternate model for the
      dysregulated expression of the prothrombin 20210A gene that does not require a
      change in the stability of its mRNA.

PMID- 12070053
TI  - Dendritic cells in the mycobacterial granuloma are involved in acquired immunity.

PMID- 12070054
TI  - Nonspecific interstitial pneumonia and systemic sclerosis.

PMID- 12070055
TI  - Inhaled glucocorticosteroids and chronic obstructive pulmonary disease: how full
      is the glass?

PMID- 12070056
TI  - Histopathologic subsets of fibrosing alveolitis in patients with systemic
      sclerosis and their relationship to outcome.
AB  - Fibrosing alveolitis associated with systemic sclerosis (FASSc) has a better
      prognosis than idiopathic pulmonary fibrosis. In view of recent reports that
      idiopathic nonspecific interstitial pneumonia (NSIP) has a better prognosis than
      idiopathic usual interstitial pneumonia (UIP), we classified histologic
      appearances of surgical lung biopsies performed in 80 patients with FASSc. NSIP
      (n = 62, 77.5%), subcategorized as cellular NSIP (n = 15) and fibrotic NSIP (n =
      47) was much more prevalent than UIP (n = 6), end-stage lung disease (ESL, n =
      6), or other patterns (n = 6). There were 25 deaths (NSIP 16/62, 26%; UIP/ESL
      6/12, 50%). Five-year survival differed little between NSIP (91%) and UIP/ESL
      (82%); mortality was associated with lower initial carbon monoxide diffusing
      capacity (DL(CO)) and FVC levels (p = 0.004 and p = 0.007, respectively).
      Survival and serial FVC and DL(CO) trends did not differ between cellular and
      fibrotic NSIP. Increased mortality in NSIP was associated with lower initial
      DL(CO) levels (p = 0.04), higher BAL eosinophil levels (p = 0.03), and
      deterioration in DL(CO) levels during the next 3 years (p < 0.005). We conclude
      that NSIP is the histopathologic pattern in most patients with FASSc. However,
      outcome is linked more strongly to disease severity at presentation and serial
      DL(CO) trends than to histopathologic findings.

PMID- 12070057
TI  - Partitioning of alveolar and conducting airway nitric oxide in scleroderma lung
      disease.
AB  - We partitioned exhaled nitric oxide (NO) into alveolar concentration (CA) and
      conducting airway flux (JNO(air,max)) in scleroderma (SSc) lung disease and
      hypothesized that CA would be elevated. Twenty patients with SSc, 15 with
      interstitial lung disease (SSc-ILD) alone, and 5 with pulmonary hypertension (SSc
      PH) were compared with 20 control subjects. CA and JNO(air,max) were derived from
      the slope and y intercept, respectively, of the NO output versus expiratory flow
      rate ((V).exh) relationship obtained by measuring exhaled NO (FE(NO)) at multiple
      (V).exh values of 50-200 ml/second. There were no significant differences in
      FE(NO) at any (V).exh between the SSc group and control subjects. JNO(air,max)
      was reduced (0.6 +/- 0.1 versus 1.2 +/- 0.2 nl of NO per second; p = 0.01),
      whereas CA was increased (4.7 +/- 0.5 versus 1.8 +/- 0.2 ppb; p < 0.001) in the
      SSc group compared with control subjects. No differences were noted between SSc
      ILD and SSc-PH. There was a negative correlation between CA and DL(CO) among the
      patients with SSc (R = -0.66, p = 0.002). We conclude that CA is increased
      whereas JNO(air,max) is decreased in SSc-ILD and SSc-PH. A reduced diffusing
      capacity of NO from the alveolar space into the blood could explain the observed
      increase in CA.

PMID- 12070058
TI  - The effects of inhaled fluticasone on airway inflammation in chronic obstructive
      pulmonary disease: a double-blind, placebo-controlled biopsy study.
AB  - Inhaled corticosteroids (ICS) are effective in the treatment of asthma and
      markedly reduce the numbers of inflammatory cells in bronchial biopsies. However,
      the effect of ICS on the inflammatory profile of biopsies in smokers with chronic
      obstructive pulmonary disease (COPD) is unknown. We have performed a double
      blind, placebo-controlled, randomized study to compare fluticasone propionate
      (FP) 500 microg twice daily via a dry powder inhaler and placebo (P) over a 3
      month period in subjects with COPD. Fiberoptic bronchoscopy and bronchial biopsy
      was carried out at baseline and after the 3 months of treatment. Thirty-one
      subjects completed the trial and 30 paired biopsies were available for analysis.
      Compared with P (n = 14), subjects on inhaled FP (n = 16) had no significant
      reductions in the primary endpoints: CD8+, CD68+ cells, or neutrophils,
      considered to be of importance in COPD. However, there was a reduction in the
      CD8:CD4 ratio in the epithelium and of the numbers of subepithelial mast cells in
      the FP group. CD4+ cells were significantly raised in the P group in both
      subepithelium and epithelium. Symptoms significantly improved, and there were
      significantly fewer exacerbations in subjects on FP, compared to subjects on P.
      The data indicate that inhaled fluticasone does affect selected aspects of airway
      inflammation in COPD, and this may explain, in part, the decrease in
      exacerbations seen in long-term studies with fluticasone propionate.

PMID- 12070059
TI  - Exhaled nitric oxide as a diagnostic test for asthma: online versus offline
      techniques and effect of flow rate.
AB  - Measurement of the fraction of exhaled nitric oxide (FENO) has been proposed as a
      noninvasive assessment of asthmatic airway inflammation. The influence of the
      expiratory flow rate during the collection maneuver on the ability of FENO to
      discriminate healthy subjects from those with asthma is unknown. We compared
      online and offline measurement of FENO at different flow rates. FENO was
      collected with expiratory flows of 50-500 ml/second in 34 patients with asthma
      (PC(20) of less than 8 mg/ml) and 28 healthy subjects (PC(20) of more than 10
      mg/ml) using offline collection techniques. In a subgroup of 18 individuals with
      asthma and 17 healthy subjects, we additionally measured FENO at multiple
      expiratory flow rates (47-250 ml/second) using online methods. FENO fell with an
      increasing expiratory flow rate; FENO was higher in subjects with asthma as
      compared with healthy subjects at each flow rate studied with both techniques (p
      < 0.001). Receiver operating characteristic (ROC) curves for the diagnosis of
      asthma indicated that FENO is a robust discriminator between individuals with
      asthma and healthy subjects (area under the ROC curves 0.79 +/- 0.06 to 0.86 +/-
      0.06, p for significant discrimination < 0.0001). Neither expiratory flow rate
      nor collection technique (online versus offline) significantly altered this
      discriminatory capacity (area under the ROC curves = 0.84 +/- 0.07 with the
      slowest online method versus 0.80 +/- 0.07 with the fastest offline method, p =
      0.46). These data indicate that the choice of expiratory flow rate and collection
      method can be based on practicality and patient comfort without compromising the
      utility of this test for asthma.

PMID- 12070060
TI  - Responses of leukocytes to chemokines in whole blood and their antagonism by
      novel CC-chemokine receptor 3 antagonists.
AB  - CC-chemokine receptor 3 (CCR3)-stimulating chemokines are likely to have
      important in vivo roles in the regulation of eosinophil, basophil, and
      potentially helper T cell type 2 and mast cell recruitment. We have developed
      techniques to investigate the actions of eotaxin and other chemokines on multiple
      leukocyte populations in whole blood, without cell purification steps that might
      alter leukocyte responsiveness. We have shown that the potency of eotaxin in
      whole blood is limited by Duffy antigen binding, which may modulate the actions
      of this chemokine in vivo. We have also investigated the efficacy and potency of
      a new panel of small molecule antagonists of CCR3 on responses of eosinophils,
      neutrophils, basophils, and monocytes to chemokines, using whole blood assays of
      shape change, chemokine receptor internalization, and CD11b upregulation. These
      small molecule antagonists cause selective and potent inhibition of CCR3 on
      eosinophils and basophils, are bioavailable in blood, and are prototypic
      antagonists potentially of benefit in the treatment of human allergic disease.
      Such whole blood methods may also be employed in the investigation of other small
      molecule chemokine receptor antagonists.

PMID- 12070061
TI  - Lung inflammation induced by concentrated ambient air particles is related to
      particle composition.
AB  - The objectives of this study were (1) to determine whether short-term exposures
      to concentrated air particles (CAPs) cause pulmonary inflammation in normal rats
      and rats with chronic bronchitis (CB); (2) to identify the site within the lung
      parenchyma where CAPs-induced inflammation occurs; and (3) to characterize the
      component(s) of CAPs that is significantly associated with the development of the
      inflammatory reaction. Four groups of animals were studied: (1) air treated,
      filtered air exposed (air-sham); (2) sulfur dioxide treated (CB), filtered air
      exposed (CB-sham); (3) air treated, CAPs exposed (air-CAPs); and (4) sulfur
      dioxide treated, CAPs exposed (CB-CAPs). CB and normal rats were exposed by
      inhalation either to filtered air or CAPs during 3 consecutive days (5
      hours/day). Pulmonary inflammation was assessed by bronchoalveolar lavage (BAL)
      and by measuring the numerical density of neutrophils (Nn) in the alveolar walls
      at the bronchoalveolar junction and in more peripheral alveoli. CAPs (as a binary
      exposure term) and CAPs mass (in regression correlations) induced a significant
      increase in BAL neutrophils and in normal and CB animals. Nn in the lung tissue
      significantly increased with CAPs in normal animals only. Greater Nn was observed
      in the central compared with peripheral regions of the lung. A significant dose
      dependent association was found between many CAPs components and BAL neutrophils
      or lymphocytes, but only vanadium and bromine concentrations had significant
      associations with both BAL neutrophils and Nn in CAPs-exposed groups analyzed
      together. Results demonstrate that short-term exposures to CAPs from Boston
      induce a significant inflammatory reaction in rat lungs, with this reaction
      influenced by particle composition.

PMID- 12070062
TI  - Reproducibility of blind protected bronchoalveolar lavage in mechanically
      ventilated children.
AB  - Blind protected bronchoalveolar lavage (BAL) could be an interesting tool in the
      diagnosis of ventilator-associated pneumonia in intubated children, but its
      reproducibility has never been evaluated. This study evaluates the
      reproducibility, feasibility, and safety of blind protected BAL in mechanically
      ventilated children. Two blind protected BAL were done, at a 2-hour interval, in
      30 patients. The reproducibility of microbiologic and cytologic results was
      studied. A total of 60 BALs was analyzed. Bacterial growth was present in 26 of
      60 BAL (43%). Reproducibility for the presence of bacteria on quantitative
      cultures was excellent (concordance, 93%; kappa [kappa], 0.86). Concordance for
      the type of bacteria isolated was 86% and for the number of bacteria was 79%.
      Reproducibility for the presence of neutrophils containing bacteria was perfect
      (concordance, 100%; kappa, 1) although only a few BALs had a positive result
      (8/60). Blind protected BAL was feasible in all patients and all samples were
      considered adequate for analysis. Complications were mostly benign and transitory
      except in two cases: one pneumothorax and one significant increase in
      intracranial pressure. Overall, blind protected BAL is a reproducible test in
      mechanically ventilated children, is easily feasible, and is usually well
      tolerated.

PMID- 12070063
TI  - Plasma vascular endothelial growth factor in sleep apnea syndrome: effects of
      nasal continuous positive air pressure treatment.
AB  - Sleep apnea syndrome is associated with recurrent episodic hypoxia during sleep,
      which has been implicated in the development of cardiovascular morbidity. Hypoxia
      is the major stimulus of vascular endothelial growth factor (VEGF), which is a
      potent angiogenic cytokine. In the present article we describe the results of
      three experiments in which plasma concentrations of VEGF were measured in
      patients with sleep apnea. In Experiment 1, apnea-hypopnea index was found to be
      a significant independent predictor of morning VEGF concentrations in 85 male
      subjects investigated in the sleep laboratory, of whom 47 had an apnea-hypopnea
      index greater than 20. In Experiment 2, VEGF concentrations measured hourly
      during the sleep period were found to be significantly higher in a group of five
      sleep apnea patients compared with six age-similar snorers and six normal young
      adults (129.1 +/- 43.4 versus 74.6 +/- 11.5 and 32.5 +/- 12.8 pg/ml, respectively
      [p < 0.007]). In Experiment 3, VEGF concentrations were compared in patients with
      sleep apnea before and 1 year after nasal continuous positive airway pressure
      treatment. A significant decrease in VEGF concentrations was found only in
      patients in whom nocturnal hypoxia improved after treatment (57.1 +/- 62.5 versus
      39.6 +/- 46.9 pg/ml, p < 0.01). There was no comparable improvement in patients
      who did not accept treatment (53.9 +/- 23.6 versus 54.0 +/- 21.5 pg/ml, ns).
      These results raise the possibility that VEGF may contribute to the long-term
      adaptation of sleep apnea syndrome to recurrent nocturnal hypoxia.

PMID- 12070064
TI  - An elevated breathing reserve index at the lactate threshold is a predictor of
      mortality in patients with cystic fibrosis awaiting lung transplantation.
AB  - The proportion of cystic fibrosis (CF) patients dying while on the lung
      transplant wait list remains high; identification of such patients remains
      difficult. The breathing reserve index (BRI = minute ventilation/maximal
      voluntary ventilation) at the lactate threshold (LT) is a predictor of a
      pulmonary mechanical limit to incremental exercise. We hypothesized that an
      elevated BRI at the LT in patients with CF awaiting lung transplantation would be
      a predictor of wait list mortality. Forty-five consecutive patients with CF
      completed cardiopulmonary exercise testing as part of their pretransplant
      assessment. We evaluated BRI at LT, baseline demographic characteristics,
      pulmonary function, and other exercise parameters via Cox proportional hazards
      modeling. Fifteen patients died while awaiting transplant. Twenty one were
      transplanted, and nine still awaited transplantation. Relative risks from the
      multivariate model included (95% confidence interval in parentheses) BRI at LT,
      17.52 (2.45-123.97); resting Pa(CO(2)), 1.29 (1.10-1.49); resting Pa(O(2)), 0.97
      (0.90-1.05); and forced expiratory volume at one second as a percent of
      predicted, 1.19 (1.05-1.34). BRI at LT not only provided the highest point
      estimate of risk for wait list mortality but also identified a physiologically
      significant threshold value (0.70 or more) for those at risk. This measurement
      may allow improved timing of listing for transplantation, including consideration
      for living donor transplantation.

PMID- 12070065
TI  - Role of inducible nitric oxide synthase in pulmonary microvascular protein leak
      in murine sepsis.
AB  - The effects of nitric oxide (NO) from calcium-independent NO synthase (iNOS) on
      microvascular protein leak in acute lung injury (ALI) are uncertain, possibly
      because of disparate effects of iNOS-derived NO from different cells. We assessed
      the contribution of iNOS from inflammatory versus parenchymal cells to pulmonary
      protein leak in murine cecal ligation and perforation-induced ALI. We studied
      iNOS+/+, iNOS-/-, and two reciprocally bone marrow-transplanted iNOS chimeric
      mice groups: + to - (iNOS+/+ donor bone marrow-transplanted into iNOS-/-
      recipient mice) and - to +. Sepsis-induced ALI was characterized by pulmonary
      leukocyte infiltration, increased pulmonary iNOS activity, and increased
      pulmonary microvascular protein leak, as assessed by Evans blue (EB) dye. Despite
      equal neutrophil infiltration, sepsis-induced EB-protein leak was eliminated in
      iNOS-/- mice and in - to + iNOS chimeras (parenchymal cell-localized iNOS) but
      was preserved in + to - chimeric mice (inflammatory cell-localized iNOS). EB
      protein leak was also prevented by pretreatment with allopurinol and superoxide
      dismutase. Microvascular protein leak in sepsis-induced ALI is uniquely dependent
      on iNOS in inflammatory cells with no obvious contribution of iNOS in pulmonary
      parenchymal cells. Pulmonary protein leak is also dependent on superoxide,
      suggesting an effect of peroxynitrite rather than NO itself.

PMID- 12070067
TI  - Perspective on lung injury and recruitment: a skeptical look at the opening and
      collapse story.

PMID- 12070066
TI  - Dendritic cell involvement in pulmonary granuloma formation elicited by bacillus
      calmette-guerin in rats.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells that play a
      central role in initiating the primary immune response. However, their role in
      granulomatous inflammation has not been well studied. The aim of the present
      study was to elucidate the role of DCs in granuloma formation. Using a rat model
      of bacillus Calmette-Guerin (BCG)-elicited pulmonary granulomas, we investigated
      the distribution of DCs in the granulomas by immunohistochemistry with a rat-DC
      specific monoclonal antibody, OX62. We found numerous large, pleiomorphic OX62(+)
      cells accumulating at the borders of the pulmonary granulomas. The OX62(+) cells
      isolated from the granulomatous lung showed intense surface expression of major
      histocompatibility complex class II, B7-1, and B7-2, and a lack of T cell- and
      monocyte/macrophage-specific markers. Their ultrastructural morphology was
      characteristic of DCs. Functionally, they had potent capacity to stimulate
      allogeneic T cells as well as purified protein derivative-specific syngeneic T
      cells in the absence of exogenous peptides. Based on these findings, the OX62(+)
      cells infiltrating the granulomas were considered to be DCs expressing BCG
      derived peptides. These results indicate that DCs contribute to pulmonary
      granuloma formation elicited by BCG by means of their potent antigen-presenting
      function, providing a novel insight into DC function in T cell-mediated
      granulomatous immune responses.

PMID- 12070068
TI  - Calcium deposition with or without bone formation in the lung.
AB  - Pulmonary calcification and ossification occurs with a number of systemic and
      pulmonary conditions. Specific symptoms are often lacking, but calcification may
      be a marker of disease severity and its chronicity. Pathophysiologic states
      predisposing to pulmonary calcification and ossification include hypercalcemia, a
      local alkaline environment, and previous lung injury. Factors such as enhanced
      alkaline phosphatase activity, active angiogenesis, and mitogenic effects of
      growth factors may also contribute. The clinical classification of pulmonary
      calcification includes both metastatic calcification, in which calcium deposits
      in previously normal lung or dystrophic calcification, which occurs in previously
      injured lung. Pulmonary ossification can be idiopathic or can result from a
      variety of underlying pulmonary, cardiac, or extracardiopulmonary disorders. The
      diagnosis of pulmonary calcification and ossification requires various imaging
      techniques, including chest radiography, computed tomographic scanning, and bone
      scintigraphy. Interpretation of the presence of and the specific pattern of
      calcification or ossification may obviate the need for invasive biopsy. In this
      review, specific conditions causing pulmonary calcification or ossification that
      may impact diagnostic and treatment decisions are highlighted. These include
      metastatic calcification caused by chronic renal failure and orthotopic liver
      transplantation, dystrophic calcification caused by granulomatous disorders, DNA
      viruses, parasitic infections, pulmonary amyloidosis, vascular calcification, the
      idiopathic disorder pulmonary alveolar microlithiasis, and various forms of
      pulmonary ossification.

PMID- 12070069
TI  - Monitoring reactive nitrogen species in biological milieu: a difficult journey.

PMID- 12070070
TI  - Transient clinical deterioration in HIV patients with Pneumocystis carinii
      pneumonia after starting highly active antiretroviral therapy: another case of
      immune restoration inflammatory syndrome.

PMID- 12070071
TI  - Rapid translocation of nanoparticles from the lung to the bloodstream?

PMID- 12070072
TI  - The presence of Lewis a epitopes in Arabidopsis thaliana glycoconjugates depends
      on an active alpha4-fucosyltransferase gene.
AB  - The presence of an alpha4-fucosyltransferase in plants was first deduced from the
      characterization of Lewis-a glycoepitopes in some N-glycans. The first plant gene
      encoding an alpha4-fucosyltransferase was recently cloned in Beta vulgaris. In
      the present paper we provide evidence for the presence of an alpha4
      fucosyltransferase in A. thaliana by measurement of this glycosyltransferase
      activity from a purified microsomal preparation and by immunolocalization of
      Le(a) epitopes on glycans N-linked to glycoproteins located to the Golgi
      apparatus and on the cell surface. The corresponding gene AtFT4 (AY026941) was
      characterized. A unique copy of this gene was found in A. thaliana genome, and a
      single AtFT4 transcript was revealed in leaves, in roots, and at a lower extent
      in flowers. The coding sequence of AtFT4 gene is interrupted by two introns
      spanning 465 bp and 84 bp, respectively. The putative 393-amino-acid protein (44
      kDa, pI: 6.59) contains an N-terminal hydrophobic region and one potential N
      glycosylation site, but AtFT4 has poor homology (less than 30%) to the other
      alpha3/4-fucosyltransferases except for motif II. When expressed in COS 7 cells
      the protein is able to transfer Fuc from GDP-Fuc to a type 1 acceptor substrate,
      but this transferase activity is detected only in the culture medium of
      transfected cells

PMID- 12070073
TI  - Extension of lipid-linked oligosaccharides is a high-priority aspect of the
      unfolded protein response: endoplasmic reticulum stress in Type I congenital
      disorder of glycosylation fibroblasts.
AB  - Asparagine (N)-linked glycans on endoplasmic reticulum (ER) glycoproteins have
      critical roles in multiple facets of protein folding and quality control.
      Inhibition of synthesis of lipid-linked oligosaccharides (LLOs), the precursors
      of N-linked glycans, causes glycoprotein misfolding. This results in ER stress
      and triggers the unfolded protein response (UPR), which consists of a set of
      adaptive events, or "aspects," including enhanced extension of LLO intermediates.
      Type I congenital disorders of glycosylation (CDGs) are characterized by
      diminished LLO synthesis and aberrant N-glycosylation. Such defects would be
      predicted to cause chronic ER stress with continuous UPR activation. We employed
      a quantitative pharmacological approach with dermal fibroblasts to show that (1)
      compared with three other well-known UPR aspects (transcriptional activation,
      inhibition of translation, and cell death), LLO extension was the most sensitive
      to ER stress; and (2) Type I CDG cells had a mild form of chronic ER stress in
      which LLO extension was continuously stress-activated, but other aspects of the
      UPR were unchanged. To our knowledge, Type I CDGs are the only human diseases
      shown to have chronic ER stress resulting from genetic defects in the ER quality
      control system. In conclusion, LLO extension has a high priority in the UPR of
      dermal fibroblasts. This suggests that cells stimulate N-glycosylation as part of
      a first line of defense against ER dysfunction. The broader implications of these
      results for the biological significance of the UPR are discussed.

PMID- 12070074
TI  - Lactobacillus helveticus glycosyltransferases: from genes to carbohydrate
      synthesis.
AB  - Bioactive carbohydrates are crucial in mediating essential biological processes,
      and their biosynthesis is an essential aspect to develop for a global view of
      their biological functions. Lactic acid bacteria display an array of diverse and
      complex carbohydrates and, therefore, are of particular interest. Here we present
      the identification of a novel exocellular polysaccharide structure and the
      corresponding gene cluster from Lactobacillus helveticus NCC2745. The development
      of a glycosyltransferase-specific enzymatic assay allowed the assignment of sugar
      specificities, which as a general approach will for the future permit a faster
      and more direct characterization of glycosyltransferase specificities. A model of
      the biosynthesis of the repeating unit is proposed. EpsE is a
      phosphoglucosyltransferase initiating the repeating unit biosynthesis by linking
      a glucose residue to a membrane-associated lipophilic acceptor. EpsF elongates
      the carbohydrate chain by forming an alpha(1,3)-Glcp linkage onto the first Glcp,
      whereas EpsG adds a backbone alpha(1,6)-Galp onto alpha-Glcp and EpsH attaches a
      alpha(1,6)-Glcp branch onto the first glucose residue. Finally, EpsI would add a
      beta(1,6)-Galp linkage onto alpha-Glcp terminating the sidechain and EpsJ would
      terminate the synthesis of the polysaccharides' repeating unit by forming a
      beta(1,3)-Galp linkage onto alpha-Galp.

PMID- 12070075
TI  - Shuttling of galectin-3 between the nucleus and cytoplasm.
AB  - In previous studies, we documented that galectin-3 (M(r) approximately 30,000) is
      a pre-mRNA splicing factor. Recently, galectin-3 was identified as a component of
      a nuclear and cytoplasmic complex, the survival of motor neuron complex, through
      its interaction with Gemin4. To test the possibility that galectin-3 may shuttle
      between the nucleus and the cytoplasm, human fibroblasts (LG-1) were fused with
      mouse fibroblasts (3T3). The monoclonal antibody NCL-GAL3, which recognizes human
      galectin-3 but not the mouse homolog, was used to monitor the localization of
      human galectin-3 in heterodikaryons. Human galectin-3 localized to both nuclei of
      a large percentage of heterodikaryons. Addition of the antibiotic leptomycin B,
      which inhibits nuclear export of galectin-3, decreased the percentage of
      heterodikaryons showing human galectin-3 in both nuclei. In a parallel
      experiment, mouse 3T3 fibroblasts, which express galectin-3, were fused with
      fibroblasts derived from a mouse in which the galectin-3 gene was inactivated.
      Mouse galectin-3 localized to both nuclei of a large percentage of
      heterodikaryons. Again, addition of leptomycin B restricted the presence of
      galectin-3 to one nucleus of a heterodikaryon. The results from both
      heterodikaryon assays suggest that galectin-3 can exit one nucleus, travel
      through the cytoplasm, and enter the second nucleus, matching the definition of
      shuttling.

PMID- 12070076
TI  - Effects of the mono- and tetrasialogangliosides GM1 and GQ1b on ATP-induced long
      term potentiation in hippocampal CA1 neurons.
AB  - The effects of the mono- and tetrasialogangliosides, GM1 and GQ1b, on ATP-induced
      long-term potentiation (LTP) were studied in CA1 neurons of guinea pig
      hippocampal slices. Application of 5 or 10 microM ATP for 10 min resulted in a
      transient depression followed by a slow augmentation of synaptic transmission,
      leading to LTP. LTP induced by treatment with 5 microM ATP was facilitated in
      hippocampal slices prepared from animals treated for 6 days with a ceramide
      analog, L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propranol, which
      stimulates ganglioside biosynthesis. In addition, LTP induced by 5 microM ATP was
      significantly enhanced when naive slices were incubated with GQ1b but not with
      GM1. These results suggest that a cooperative effect between extracellular ATP
      and GQ1b enhances ATP-induced LTP in hippocampal CA1 neurons. In addition, the
      LTP induced by 10 microM ATP was blocked by coapplication of the NMDA antagonist
      AP5 (5 microM or 50 microM), and this effect was partially inhibited by GQ1b
      pretreatment of the slices, suggesting that in hippocampal CA1 neurons, the
      enhancing effect of GQ1b on ATP-induced LTP is mediated by modulation of NMDA
      receptors/Ca(2+) channels.

PMID- 12070077
TI  - Effects of chemically modified heparin on Chlamydia trachomatis serovar L2
      infection of eukaryotic cells in culture.
AB  - The mechanism and inhibitors of Chlamydia trachomatis serovar L2 infection of
      eukaryotic host cells were studied using a tissue culture model infection system.
      Potent inhibition of infectivity was observed when elementary bodies (EBs) were
      exposed to heparin or when HeLa 229 cells were treated with heparinase. No
      significant inhibition was seen the other way around. The same potent inhibition
      was observed when EBs were exposed to chemically 2-O-desulfated heparin (2-ODS
      heparin), which is composed of repeating disaccharide units of IdoA-GlcNS(6S),
      but not when exposed to chemically 6-ODS heparin or completely desulfated and N
      resulfated heparin, which is composed of repeating disaccharide units of IdoA(2S)
      GlcNS or IdoA-GlcNS, respectively. The inhibitory effects of 2-ODS heparin could
      be seen only with oligosaccharides longer than dodecasaccharides. The mutant
      Chinese hamster ovary (CHO) cell line 677, which is deficient in the biosynthesis
      of heparan sulfate, was less sensitive to C. trachomatis infection than were wild
      type CHO cells. F-17 cells, deficient in 2-O-sulfation of heparan sulfate, had
      the same sensitivity to infection as wild-type CHO cells did. These data suggest
      that infection of host cells by EBS results from the specific binding of ligand
      molecules with affinity for heparin on the EB surface to heparan sulfate
      proteoglycans on the host cell surface. This binding may depend on host cell
      heparan sulfate chains that are 6-O-sulfated and longer than dodecasaccharides.
      The 2-ODS heparin oligosaccharides may be a potential agent for the prevention of
      C. trachomatis infection.

PMID- 12070078
TI  - Analyses of dolichol pyrophosphate-linked oligosaccharides in cell cultures and
      tissues by fluorophore-assisted carbohydrate electrophoresis.
AB  - Lipid-linked oligosaccharides (LLOs) are the precursors of asparagine (N)-linked
      glycans, which are essential information carriers in many biological systems, and
      defects in LLO synthesis cause Type I congenital disorders of glycosylation. Due
      to the low abundance of LLOs and the limitations of the chemical and physical
      methods previously used to detect them, simple and sensitive nonradioactive
      methods for LLO analysis are lacking. Thus, almost all studies of LLO synthesis
      have relied on metabolic labeling of the oligosaccharides with radioactive sugar
      precursors. We report that LLOs in cell cultures and tissues can be easily
      detected and quantified with a sensitivity of 1-2 pmol by fluorophore-assisted
      carbohydrate electrophoresis (FACE). These analyses required efficient removal of
      contaminants, most likely trace quantities of glycogen breakdown products, that
      interfered with FACE. Studies with CHO-K1 cells showed that LLOs detected by FACE
      and by metabolic labeling had similar turnover rates. Glc(3)Man(9)GlcNAc(2)-P-P
      dolichol was the most prominent LLO detected by FACE in normal cultured cells and
      mouse tissues. However, the relative amounts of Glc(0-2)Man(5-9)GlcNAc(2)-P-P
      dolichol intermediates in tissues, such as liver and kidney, were unexpectedly
      greater than for cultured cells. IV injection of D-mannose, raising the
      circulatory concentration by three- to fourfold, did not affect LLO composition.
      Thus, the relative accumulation of LLO intermediates in mouse liver and kidney is
      not likely due to inadequate D-mannose in the circulation. In summary, FACE is a
      facile, accurate, and sensitive method for LLO analysis, permitting
      investigations not feasible by metabolic labeling.

PMID- 12070079
TI  - The last common bilaterian ancestor.
AB  - Many regulatory genes appear to be utilized in at least superficially similar
      ways in the development of particular body parts in Drosophila and in chordates.
      These similarities have been widely interpreted as functional homologies,
      producing the conventional view of the last common protostome-deuterostome
      ancestor (PDA) as a complex organism that possessed some of the same body parts
      as modern bilaterians. Here we discuss an alternative view, in which the last
      common PDA had a less complex body plan than is frequently conceived. This
      reconstruction alters expectations for Neoproterozoic fossil remains that could
      illustrate the pathways of bilaterian evolution.

PMID- 12070080
TI  - Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and
      thyroid.
AB  - Eyes absent (Eya) genes regulate organogenesis in both vertebrates and
      invertebrates. Mutations in human EYA1 cause congenital Branchio-Oto-Renal (BOR)
      syndrome, while targeted inactivation of murine Eya1 impairs early developmental
      processes in multiple organs, including ear, kidney and skeletal system. We have
      now examined the role of Eya1 during the morphogenesis of organs derived from the
      pharyngeal region, including thymus, parathyroid and thyroid. The thymus and
      parathyroid are derived from 3rd pharyngeal pouches and their development is
      initiated via inductive interactions between neural crest-derived arch
      mesenchyme, pouch endoderm, and possibly the surface ectoderm of 3rd pharyngeal
      clefts. Eya1 is expressed in all three cell types during thymus and parathyroid
      development from E9.5 and the organ primordia for both of these structures failed
      to form in Eya1(-/-) embryos. These results indicate that Eya1 is required for
      the initiation of thymus and parathyroid gland formation. Eya1 is also expressed
      in the 4th pharyngeal region and ultimobranchial bodies. Eya1(-/-) mice show
      thyroid hypoplasia, with severe reduction in the number of parafollicular cells
      and the size of the thyroid lobes and lack of fusion between the ultimobranchial
      bodies and the thyroid lobe. These data indicate that Eya1 also regulates mature
      thyroid gland formation. Furthermore, we show that Six1 expression is markedly
      reduced in the arch mesenchyme, pouch endoderm and surface ectoderm in the
      pharyngeal region of Eya1(-/-) embryos, indicating that Six1 expression in those
      structures is Eya1 dependent. In addition, we show that in Eya1(-/-) embryos, the
      expression of Gcm2 in the 3rd pouch endoderm is undetectable at E10.5, however,
      the expression of Hox and Pax genes in the pouch endoderm is preserved at E9.5
      10.5. Finally, we found that the surface ectoderm of the 3rd and 4th pharyngeal
      region show increased cell death at E10.5 in Eya1(-/-) embryos. Our results
      indicate that Eya1 controls critical early inductive events involved in the
      morphogenesis of thymus, parathyroid and thyroid.

PMID- 12070082
TI  - Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic
      development.
AB  - Despite its evolutionary conservation and functional importance, little is known
      of the signaling pathways that underlie development of the hypothalamus. Although
      mutations affecting Nodal and Hedgehog signaling disrupt hypothalamic
      development, the time and site of action and the exact roles of these pathways
      remain very poorly understood. Unexpectedly, we show here that cell-autonomous
      reception of Nodal signals is neither required for the migration of hypothalamic
      precursors within the neural plate, nor for further development of the anterior
      dorsal hypothalamus. Nodal signaling is, however, cell-autonomously required for
      establishment of the posterior-ventral hypothalamus. Conversely, Hedgehog
      signaling antagonizes the development of posterior-ventral hypothalamus, while
      promoting anterior-dorsal hypothalamic fates. Besides their distinct roles in the
      regionalization of the diencephalon, we reveal cooperation between Nodal and
      Hedgehog pathways in the maintenance of the anterior-dorsal hypothalamus. Finally
      we show that it is the prechordal plate and not the head endoderm that provides
      the early signals essential for establishment of the hypothalamus.

PMID- 12070081
TI  - Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the
      dorsal telencephalon.
AB  - Pattern formation of the dorsal telencephalon is governed by a regionalisation
      process that leads to the formation of distinct domains, including the future
      hippocampus and neocortex. Recent studies have implicated signalling proteins of
      the Wnt and Bmp gene families as well as several transcription factors, including
      Gli3 and the Emx homeobox genes, in the molecular control of this process. The
      regulatory relationships between these genes, however, remain largely unknown. We
      have used transgenic analysis to investigate the upstream mechanisms for
      regulation of Emx2 in the dorsal telencephalon. We have identified an enhancer
      from the mouse Emx2 gene that drives specific expression of a lacZ reporter gene
      in the dorsal telencephalon. This element contains binding sites for Tcf and Smad
      proteins, transcriptional mediators of the Wnt and Bmp signalling pathway,
      respectively. Mutations of these binding sites abolish telencephalic enhancer
      activity, while ectopic expression of these signalling pathways leads to ectopic
      activation of the enhancer. These results establish Emx2 as a direct
      transcriptional target of Wnt and Bmp signalling and provide insights into a
      genetic hierarchy involving Gli3, Emx2 and Bmp and Wnt genes in the control of
      dorsal telencephalic development.

PMID- 12070083
TI  - Vitamin D(3) receptor ablation alters mammary gland morphogenesis.
AB  - Postnatal mammary gland morphogenesis is achieved through coordination of
      signaling networks in both the epithelial and stromal cells of the developing
      gland. While the major proliferative hormones driving pubertal mammary gland
      development are estrogen and progesterone, studies in transgenic and knockout
      mice have successfully identified other steroid and peptide hormones that impact
      on mammary gland development. The vitamin D(3) receptor (VDR), whose ligand 1,25
      dihydroxyvitamin D(3) is the biologically active form of vitamin D(3), has been
      implicated in control of differentiation, cell cycle and apoptosis of mammary
      cells in culture, but little is known about the physiological relevance of the
      vitamin D(3) endocrine system in the developing gland. In these studies, we
      report the expression of the VDR in epithelial cells of the terminal end bud and
      subtending ducts, in stromal cells and in a subset of lymphocytes within the
      lymph node. In the terminal end bud, a distinct gradient of VDR expression is
      observed, with weak VDR staining in proliferative populations and strong VDR
      staining in differentiated populations. The role of the VDR in ductal
      morphogenesis was examined in Vdr knockout mice fed high dietary Ca(2+) which
      normalizes fertility, serum estrogen and neonatal growth. Our results indicate
      that mammary glands from virgin Vdr knockout mice are heavier and exhibit
      enhanced growth, as evidenced by higher numbers of terminal end buds, greater
      ductal outgrowth and enhanced secondary branch points, compared with glands from
      age- and weight-matched wild-type mice. In addition, glands from Vdr knockout
      mice exhibit enhanced growth in response to exogenous estrogen and progesterone,
      both in vivo and in organ culture, compared with glands from wild-type mice. Our
      data provide the first in vivo evidence that 1,25-dihydroxyvitamin D(3) and the
      VDR impact on ductal elongation and branching morphogenesis during pubertal
      development of the mammary gland. Collectively, these results suggest that the
      vitamin D(3) signaling pathway participates in negative growth regulation of the
      mammary gland.

PMID- 12070084
TI  - Misexpression of dHAND induces ectopic digits in the developing limb bud in the
      absence of direct DNA binding.
AB  - Basic helix-loop-helix (bHLH) transcription factors control developmental
      decisions in a wide range of embryonic cell types. The HLH motif mediates homo-
      and heterodimerization, which juxtaposes the basic regions within the dimeric
      complex to form a bipartite DNA binding domain that recognizes a DNA consensus
      sequence known as an E-box. eHAND and dHAND (also known as HAND1 and HAND2) are
      closely related bHLH proteins that control cardiac, craniofacial and limb
      development. Within the developing limb, dHAND expression encompasses the zone of
      polarizing activity in the posterior region, where it has been shown to be
      necessary and sufficient to induce the expression of the morphogen sonic
      hedgehog. Misexpression of dHAND in the anterior compartment of the limb bud
      induces ectopic expression of sonic hedgehog, with resulting preaxial polydactyly
      and mirror image duplications of posterior digits. To investigate the potential
      transcriptional mechanisms involved in limb patterning by dHAND, we have
      performed a structure-function analysis of the protein in cultured cells and
      ectopically expressed dHAND mutant proteins in the developing limbs of transgenic
      mice. We show that an N-terminal transcriptional activation domain, and the bHLH
      region, are required for E-box-dependent transcription in vitro. Remarkably,
      however, digit duplication by dHAND requires neither the transcriptional
      activation domain nor the basic region, but only the HLH motif. eHAND has a
      similar limb patterning activity to dHAND in these misexpression experiments,
      indicating a conserved function of the HLH regions of these proteins. These
      findings suggest that dHAND may act via novel transcriptional mechanisms mediated
      by protein-protein interactions independent of direct DNA binding.

PMID- 12070085
TI  - Effects of heterodimerization and proteolytic processing on Derriere and Nodal
      activity: implications for mesoderm induction in Xenopus.
AB  - Derriere is a recently discovered member of the TGFbeta superfamily that can
      induce mesoderm in explant assays and is expressed at the right time and location
      to mediate mesoderm induction in response to VegT during Xenopus embryogenesis.
      We show that the ability of Derriere to induce dorsal or ventral mesoderm depends
      strictly on the location of expression and that a dominant-negative Derriere
      cleavage mutant completely blocks all mesoderm formation when ectopically
      expressed. This differs from the activity of similar Xnr2 cleavage mutant
      constructs, which are secreted and retain signaling activity. Additional analysis
      of mesoderm induction by Derriere and members of the Nodal family indicates that
      these molecules are involved in a mutual positive-feedback loop and antagonism of
      either one of the signals can reduce the other. Interaction between Derriere and
      members of the Nodal family is also shown to occur through the formation of
      heterodimeric ligands. Using an oocyte expression system we show direct
      interaction between the mature Derriere ligand and members of both the Nodal and
      BMP families. Taken together, these findings indicate that Derriere and Nodal
      proteins probably work cooperatively to induce mesoderm throughout the marginal
      zone during early Xenopus development.

PMID- 12070086
TI  - Tail regression in Ciona intestinalis (Prochordate) involves a Caspase-dependent
      apoptosis event associated with ERK activation.
AB  - Two apoptotic events take place during embryonic development of Ciona
      intestinalis. The first concerns extra-embryonic cells and precedes hatching. The
      second controls tail regression at metamorphosis, occurs through a polarized wave
      originating from tail extremity, and is caspase dependent. This was shown by: (1)
      in vivo incorporation of a fluorescent marker of caspase activation in different
      cell types of the tail; (2) detection of an activated form of caspase 3-like
      protein by western blotting; and (3) failure of 30% of larvae to undergo
      metamorphosis after treatment of fertilized eggs with a pan-caspase inhibitor. In
      addition, Ciona embryos express a single ERK protein, specifically phosphorylated
      at metamorphosis. ERK activation was shown to be located in cells of the tail.
      Addition of MEK inhibitor in the culture medium prevented ERK activation and
      metamorphosis. In silico analysis of Ciona genome pointed to 15 caspases with
      high homology with humans, and a single ERK gene with high homology to both
      mammalian ERK1 and ERK2. It is concluded that the sequence of events leading to
      metamorphosis includes ERK phosphorylation followed by caspase-dependent
      apoptosis and tail regression.

PMID- 12070087
TI  - Hox repression of a target gene: extradenticle-independent, additive action
      through multiple monomer binding sites.
AB  - Homeotic (Hox) genes regulate the identity of structures along the anterior
      posterior axis of most animals. The low DNA-binding specificities of Hox proteins
      have raised the question of how these transcription factors selectively regulate
      target gene expression. The discovery that the Extradenticle (Exd)/Pbx and
      Homothorax (Hth)/Meis proteins act as cofactors for several Hox proteins has
      advanced the view that interactions with cofactors are critical to the target
      selectivity of Hox proteins. It is not clear, however, to what extent Hox
      proteins also regulate target genes in the absence of cofactors. In Drosophila
      melanogaster, the Hox protein Ultrabithorax (Ubx) promotes haltere development
      and suppresses wing development by selectively repressing many genes of the wing
      patterning hierarchy, and this activity requires neither Exd nor Hth function.
      Here, we show that Ubx directly regulates a flight appendage-specific cis
      regulatory element of the spalt (sal) gene. We find that multiple monomer Ubx
      binding sites are required to completely repress this cis-element in the haltere,
      and that individual Ubx-binding sites are sufficient to mediate its partial
      repression. These results suggest that Hox proteins can directly regulate target
      genes in the absence of the cofactor Extradenticle. We propose that the
      regulation of some Hox target genes evolves via the accumulation of multiple Hox
      monomer binding sites. Furthermore, because the development and morphological
      diversity of the distal parts of most arthropod and vertebrate appendages involve
      Hox, but not Exd/Pbx or Hth/Meis proteins, this mode of target gene regulation
      appears to be important for distal appendage development and the evolution of
      appendage diversity.

PMID- 12070088
TI  - Concerted action of two dlx paralogs in sensory placode formation.
AB  - Sensory placodes are ectodermal thickenings that give rise to elements of the
      vertebrate cranial sensory nervous system, including the inner ear and nose.
      Although mutations have been described in humans, mice and zebrafish that perturb
      ear and nose development, no mutation is known to prevent sensory placode
      formation. Thus, it has been postulated that a functional redundancy exists in
      the genetic mechanisms that govern sensory placode development. We describe a
      zebrafish deletion mutation, b380, which results in a lack of both otic and
      olfactory placodes. The b380 deletion removes several known genes and expressed
      sequence tags, including dlx3 and dlx7, two transcription factors that share a
      homoeobox domain similar in sequence to the Drosophila Distal-less gene. dlx3 and
      dlx7 are expressed in an overlapping pattern in the regions that produce the otic
      and olfactory placodes in zebrafish. We present evidence suggesting that it is
      specifically the removal of these two genes that leads to the otic and olfactory
      phenotype of b380 mutants. Using morpholinos, antisense oligonucleotides that
      effectively block translation of target genes, we find that functional reduction
      of both dlx genes contributes to placode loss. Expression patterns of the otic
      marker pax2.1, olfactory marker anxV and eya1, a marker of both placodes, in
      morpholino-injected embryos recapitulate the reduced expression of these genes
      seen in b380 mutants. We also examine expression of dlx3 and dlx7 in the
      morpholino-injected embryos and present evidence for existence of auto- and cross
      regulatory control of expression among these genes. We demonstrate that dlx3 is
      necessary and sufficient for proper otic and olfactory placode development.
      However, our results indicate that dlx3 and dlx7 act in concert and their
      importance in placode formation is only revealed by inactivating both paralogs.

PMID- 12070089
TI  - Zebrafish mutants identify an essential role for laminins in notochord formation.
AB  - Basement membranes are thought to be essential for organ formation, providing the
      scaffold on which individual cells organize to form complex tissues. Laminins are
      integral components of basement membranes. To understand the development of a
      simple vertebrate organ, we have used positional cloning to characterize grumpy
      and sleepy, two zebrafish loci known to control notochord formation, and find
      that they encode laminin beta1 and laminin gamma1, respectively. Removal of
      either chain results in the dramatic loss of laminin 1 staining throughout the
      embryo and prevents formation of the basement membrane surrounding the notochord.
      Notochord cells fail to differentiate and many die by apoptosis. By
      transplantation, we demonstrate that, for both grumpy and sleepy, notochord
      differentiation can be rescued by exogenous sources of the missing laminin chain,
      although notochordal sources are also sufficient for rescue. These results
      demonstrate a clear in vivo requirement for laminin beta1 and laminin gamma1 in
      the formation of a specific vertebrate organ and show that laminin or the laminin
      dependent basement membrane is essential for the differentiation of
      chordamesoderm to notochord.

PMID- 12070090
TI  - Control of cortical interneuron migration by neurotrophins and PI3-kinase
      signaling.
AB  - During telencephalic development, cells from the medial ganglionic eminence (MGE)
      are thought to migrate to the neocortex to give rise to a majority of cortical
      GABAergic interneurons. By combining time-lapse video-microscopy,
      immunofluorescence and pharmacological perturbations in a new in vitro migration
      assay, we find that MGE-derived cells migrate through the entire extent of the
      cortex and into the CA fields of the hippocampus, but avoid the dentate gyrus.
      Migrating neurons initially travel within the marginal zone and intermediate
      zone, and can enter the cortical plate from either location. Tangential migration
      is strongly stimulated by BDNF and NT4 and attenuated by the Trk-family
      inhibitor, K252a, suggesting that migration is regulated by TrkB signaling.
      Furthermore, TrkB-null mice show a significant decrease in the number of
      calbindin-positive neurons migrating tangentially in the embryonic cortex. BDNF
      and NT4 cause rapid activation of PI3-kinase in MGE cells, and inhibition of PI3
      kinase (but not of MAP kinase or PLCgamma) dramatically attenuates tangential
      migration. These observations suggest that TrkB signaling, via PI3-kinase
      activation, plays an important role in controlling interneuron migration in the
      developing cerebral cortex.

PMID- 12070092
TI  - Drosophila RhoA regulates the cytoskeleton and cell-cell adhesion in the
      developing epidermis.
AB  - The small GTPase Rho is a molecular switch that is best known for its role in
      regulating the actomyosin cytoskeleton. We have investigated its role in the
      developing Drosophila embryonic epidermis during the process of dorsal closure.
      By expressing the dominant negative DRhoA(N19) construct in stripes of epidermal
      cells, we confirm that Rho function is required for dorsal closure and
      demonstrate that it is necessary to maintain the integrity of the ventral
      epidermis. We show that defects in actin organization, nonmuscle myosin II
      localization, the regulation of gene transcription, DE-cadherin-based cell-cell
      adhesion and cell polarity underlie the effects of DRhoA(N19) expression.
      Furthermore, we demonstrate that these changes in cell physiology have a
      differential effect on the epidermis that is dependent upon position in the
      dorsoventral axis. In the ventral epidermis, cells either lose their adhesiveness
      and fall out of the epidermis or undergo apoptosis. At the leading edge, cells
      show altered adhesive properties such that they form ectopic contacts with other
      DRhoA(N19)-expressing cells.

PMID- 12070091
TI  - The role of bone morphogenetic proteins in the differentiation of the ventral
      optic cup.
AB  - The ventral region of the chick embryo optic cup undergoes a complex process of
      differentiation leading to the formation of four different structures: the neural
      retina, the retinal pigment epithelium (RPE), the optic disk/optic stalk, and the
      pecten oculi. Signaling molecules such as retinoic acid and sonic hedgehog have
      been implicated in the regulation of these phenomena. We have now investigated
      whether the bone morphogenetic proteins (BMPs) also regulate ventral optic cup
      development. Loss-of-function experiments were carried out in chick embryos in
      ovo, by intraocular overexpression of noggin, a protein that binds several BMPs
      and prevents their interactions with their cognate cell surface receptors. At
      optic vesicle stages of development, this treatment resulted in microphthalmia
      with concomitant disruption of the developing neural retina, RPE and lens. At
      optic cup stages, however, noggin overexpression caused colobomas, pecten
      agenesis, replacement of the ventral RPE by neuroepithelium-like tissue, and
      ectopic expression of optic stalk markers in the region of the ventral retina and
      RPE. This was frequently accompanied by abnormal growth of ganglion cell axons,
      which failed to enter the optic nerve. The data suggest that endogenous BMPs have
      significant effects on the development of ventral optic cup structures.

PMID- 12070093
TI  - Competency of embryonic cardiomyocytes to undergo Purkinje fiber differentiation
      is regulated by endothelin receptor expression.
AB  - Purkinje fibers of the cardiac conduction system differentiate from heart muscle
      cells during embryogenesis. In the avian heart, Purkinje fiber differentiation
      takes place along the endocardium and coronary arteries. To date, only the
      vascular cytokine endothelin (ET) has been demonstrated to induce embryonic
      cardiomyocytes to differentiate into Purkinje fibers. This ET-induced Purkinje
      fiber differentiation is mediated by binding of ET to its transmembrane receptors
      that are expressed by myocytes. Expression of ET converting enzyme 1, which
      produces a biologically active ET ligand, begins in cardiac endothelia, both
      arterial and endocardial, at initiation of conduction cell differentiation and
      continues throughout heart development. Yet, the ability of cardiomyocytes to
      convert their phenotype in response to ET declines as embryos mature. Therefore,
      the loss of responsiveness to the inductive signal appears not to be associated
      with the level of ET ligand in the heart. This study examines the role of ET
      receptors in this age-dependent loss of inductive responsiveness and the
      expression profiles of three different types of ET receptors, ET(A), ET(B) and
      ET(B2), in the embryonic chick heart. Whole-mount in situ hybridization analyses
      revealed that ET(A) was ubiquitously expressed in both ventricular and atrial
      myocardium during heart development, while ET(B) was predominantly expressed in
      the atrium and the left ventricle. ET(B2) expression was detected in valve
      leaflets but not in the myocardium. RNase protection assays showed that
      ventricular expression of ET(A) and ET(B) increased until Purkinje fiber
      differentiation began. Importantly, the levels of both receptor isotypes
      decreased after this time. Retrovirus-mediated overexpression of ET(A) in
      ventricular myocytes in which endogenous ET receptors had been downregulated,
      enhanced their responsiveness to ET, allowing them to differentiate into
      conduction cells. These results suggest that the developmentally regulated
      expression of ET receptors plays a crucial role in determining the competency of
      ventricular myocytes to respond to inductive ET signaling in the chick embryo.

PMID- 12070094
TI  - The WUSCHEL and SHOOTMERISTEMLESS genes fulfil complementary roles in Arabidopsis
      shoot meristem regulation.
AB  - Continuous organ formation from the shoot apical meristem requires the
      integration of two functions: a set of undifferentiated, pluripotent stem cells
      is maintained at the very tip of the meristem, while their daughter cells in the
      periphery initiate organ primordia. The homeobox genes WUSCHEL (WUS) and
      SHOOTMERISTEMLESS (STM) encode two major regulators of meristem formation and
      maintenance in Arabidopsis, yet their interaction in meristem regulation is
      presently unclear. Here, we have addressed this question using loss- and gain-of
      function approaches. We show that stem cell specification by WUS does not require
      STM activity. Conversely, STM suppresses differentiation independently of WUS and
      is required and sufficient to promote cell division. Consistent with their
      independent and distinct phenotypic effects, ectopic WUS and STM activities
      induce the expression of different downstream target genes. Finally, the pathways
      regulated by WUS and STM appear to converge in the suppression of
      differentiation, since coexpression of both genes produced a synergistic effect,
      and increased WUS activity could partly compensate for loss of STM function.
      These results suggest that WUS and STM share labour in the shoot apical meristem:
      WUS specifies a subset of cells in the centre as stem cells, while STM is
      required to suppress differentiation throughout the meristem dome, thus allowing
      stem cell daughters to be amplified before they are incorporated into organs.

PMID- 12070095
TI  - Combined SHOOT MERISTEMLESS and WUSCHEL trigger ectopic organogenesis in
      Arabidopsis.
AB  - Almost all aerial parts of plants are continuously generated at the shoot apical
      meristem (SAM). To maintain a steady pool of undifferentiated cells in the SAM
      while continuously generating new organs, it is necessary to balance the rate of
      cell division with the rate of entrance into differentiation pathways. In the
      Arabidopsis meristem, SHOOT MERISTEMLESS (STM) and WUSCHEL (WUS) are necessary to
      keep cells undifferentiated and dividing. Here, we tested whether ectopic STM and
      WUS functions are sufficient to revert differentiation and activate cell division
      in differentiating tissues. Ectopic STM and WUS functions interacted non
      additively and activated a subset of meristem functions, including cell division,
      CLAVATA1 expression and organogenesis, but not correct phyllotaxy or meristem
      self-maintenance. Our results suggest that WUS produces a non-cell autonomous
      signal that activates cell division in combination with STM and that combined
      WUS/STM functions can initiate the progression from stem cells to organ
      initiation.

PMID- 12070096
TI  - Investigation of the role of cell-cell interactions in division plane
      determination during maize leaf development through mosaic analysis of the
      tangled mutation.
AB  - Most plant cells divide in planes that can be predicted from their shapes
      according to simple geometrical rules, but the division planes of some cells
      appear to be influenced by extracellular cues. In the maize leaf, some cells
      divide in orientations not predicted by their shapes, raising the possibility
      that cell-cell communication plays a role in division plane determination in this
      tissue. We investigated this possibility through mosaic analysis of the tangled
      (tan) mutation, which causes a high frequency of cells in all tissue layers to
      divide in abnormal orientations. Clonal sectors of tan mutant tissue marked by a
      closely linked albino mutation were examined to determine the phenotypes of cells
      near sector boundaries. We found that tan mutant cells always showed the mutant
      phenotype regardless of their proximity to wild-type cells, demonstrating that
      the wild-type Tan gene acts cell-autonomously in both lateral and transverse leaf
      dimensions to promote normally oriented divisions. However, if the normal
      division planes of wild-type cells depend on cell-cell communication involving
      the products of genes other than Tan, then aberrantly dividing tan mutant cells
      might send abnormal signals that alter the division planes of neighboring cells.
      The cell-autonomy of the tan mutation allowed us to investigate this possibility
      by examining wild-type cells near the boundaries of tan mutant sectors for
      evidence of aberrantly oriented divisions. We found that wild-type cells near tan
      mutant cells did not divide differently from other wild-type cells. These
      observations argue against the idea that the division planes of proliferatively
      dividing maize leaf epidermal cells are governed by short-range communication
      with their nearest neighbors.

PMID- 12070097
TI  - A novel positive transcriptional feedback loop in midbrain-hindbrain boundary
      development is revealed through analysis of the zebrafish pax2.1 promoter in
      transgenic lines.
AB  - The pax2.1 gene encodes a paired-box transcription factor that is one of the
      earliest genes to be specifically activated in development of the midbrain and
      midbrain-hindbrain boundary (MHB), and is required for the development and
      organizer activity of this territory. To understand how this spatially restricted
      transcriptional activity of pax2.1 is achieved, we have isolated and
      characterized the pax2.1-promoter using a lacZ and a GFP reporter gene in
      transient injection assays and transgenic lines. Stable transgenic expression of
      this reporter gene shows that a 5.3-kb fragment of the 5' region contains most,
      but not all, elements required for driving pax2.1 expression. The expressing
      tissues include the MHB, hindbrain, spinal cord, ear and pronephros. Transgene
      activation in the pronephros and developing ear suggests that these pax2.1
      expressing tissues are composed of independently regulated subdomains. In
      addition, ectopic but spatially restricted activation of the reporter genes in
      rhombomeres 3 and 5 and in the forebrain, which do not normally express
      endogenous pax2.1, demonstrates the importance of negative regulation of pax2.1.
      Comparison of transgene expression in wild-type and homozygous pax2.1 mutant no
      isthmus (noi) embryos reveals that the transgene contains control element(s) for
      a novel, positive transcriptional feedback loop in MHB development. Transcription
      of endogenous pax2.1 at the MHB is known to be initially Pax2.1 independent,
      during activation in late gastrulation. In contrast, transgene expression
      requires the endogenous Pax2.1 function. Transplantations, mRNA injections and
      morpholino knock-down experiments show that this feedback regulation of pax2.1
      transcription occurs cell-autonomously, and that it requires eng2 and eng3 as
      known targets for Pax2.1 regulation. We suggest that this novel feedback loop may
      allow continuation of pax2.1 expression, and hence development of the MHB
      organizer, to become independent of the patterning machinery of the gastrula
      embryo.

PMID- 12070098
TI  - Pericardin, a Drosophila type IV collagen-like protein is involved in the
      morphogenesis and maintenance of the heart epithelium during dorsal ectoderm
      closure.
AB  - The steps that lead to the formation of a single primitive heart tube are highly
      conserved in vertebrate and invertebrate embryos. Concerted migration of the two
      lateral cardiogenic regions of the mesoderm and endoderm (or ectoderm in
      invertebrates) is required for their fusion at the midline of the embryo.
      Morphogenetic signals are involved in this process and the extracellular matrix
      has been proposed to serve as a link between the two layers of cells. Pericardin
      (Prc), a novel Drosophila extracellular matrix protein is a good candidate to
      participate in heart tube formation. The protein has the hallmarks of a type IV
      collagen alpha-chain and is mainly expressed in the pericardial cells at the
      onset of dorsal closure. As dorsal closure progresses, Pericardin expression
      becomes concentrated at the basal surface of the cardioblasts and around the
      pericardial cells, in close proximity to the dorsal ectoderm. Pericardin is
      absent from the lumen of the dorsal vessel. Genetic evidence suggests that Prc
      promotes the proper migration and alignment of heart cells. Df(3)vin6 embryos, as
      well as embryos in which prc has been silenced via RNAi, exhibit similar and
      significant defects in the formation of the heart epithelium. In these embryos,
      the heart epithelium appears disorganized during its migration to the dorsal
      midline. By the end of embryonic development, cardial and pericardial cells are
      misaligned such that small clusters of both cell types appear in the heart; these
      clusters of cells are associated with holes in the walls of the heart. A prc
      transgene can partially rescue each of these phenotypes, suggesting that prc
      regulates these events. Our results support, for the first time, the function of
      a collagen-like protein in the coordinated migration of dorsal ectoderm and heart
      cells.

PMID- 12070099
TI  - Daughterless coordinates somatic cell proliferation, differentiation and germline
      cyst survival during follicle formation in Drosophila.
AB  - During Drosophila oogenesis two distinct stem cell populations produce either
      germline cysts or the somatic cells that surround each cyst and separate each
      formed follicle. From analyzing daughterless (da) loss-of-function,
      overexpression and genetic interaction phenotypes, we have identified several
      specific requirements for da(+) in somatic cells during follicle formation.
      First, da is a critical regulator of somatic cell proliferation. Also, da is
      required for the complete differentiation of polar and stalk cells, and elevated
      da levels can even drive the convergence and extension that is characteristic of
      interfollicular stalks. Finally, da is a genetic regulator of an early checkpoint
      for germline cyst progression: Loss of da function inhibits normally occurring
      apoptosis of germline cysts at the region 2a/2b boundary of the germarium, while
      da overexpression leads to postmitotic cyst degradation. Collectively, these da
      functions govern the abundance and diversity of somatic cells as they coordinate
      with germline cysts to form functional follicles.

PMID- 12070100
TI  - A pathway of signals regulating effector and initiator caspases in the developing
      Drosophila eye.
AB  - Regulated cell death and survival play important roles in neural development.
      Extracellular signals are presumed to regulate seven apparent caspases to
      determine the final structure of the nervous system. In the eye, the EGF
      receptor, Notch, and intact primary pigment and cone cells have been implicated
      in survival or death signals. An antibody raised against a peptide from human
      caspase 3 was used to investigate how extracellular signals controlled spatial
      patterning of cell death. The antibody crossreacted specifically with dying
      Drosophila cells and labelled the activated effector caspase Drice. It was found
      that the initiator caspase Dronc and the proapoptotic gene head involution
      defective were important for activation in vivo. Dronc may play roles in dying
      cells in addition to activating downstream effector caspases. Epistasis
      experiments ordered EGF receptor, Notch, and primary pigment and cone cells into
      a single pathway that affected caspase activity in pupal retina through hid and
      Inhibitor of Apoptosis Proteins. None of these extracellular signals appeared to
      act by initiating caspase activation independently of hid. Taken together, these
      findings indicate that in eye development spatial regulation of cell death and
      survival is integrated through a single intracellular pathway.

PMID- 12070102
TI  - Wine, beer, and spirits: are they really horses of a different color?

PMID- 12070103
TI  - Initial clinical experience with the Jarvik 2000 implantable axial-flow left
      ventricular assist system.

PMID- 12070104
TI  - Improving outcomes in heart failure: It's not unusual beyond usual care.

PMID- 12070105
TI  - Reperfusion for ST-segment elevation myocardial infarction: an overview of
      current treatment options.

PMID- 12070106
TI  - Mental stress induces prolonged endothelial dysfunction via endothelin-A
      receptors.
AB  - BACKGROUND: Mental stress is a risk factor for atherosclerosis and may
      precipitate myocardial ischemia and infarction. Because endothelial dysfunction
      is an early manifestation of atherosclerosis, we investigated the impact of
      mental stress on endothelial function. Methods and Results- The effects of a 3
      minute mental stress task on endothelium-dependent vasodilation were studied in
      healthy subjects without cardiovascular risk factors. Flow-mediated (FMD) and
      nitroglycerin (0.4 mg sublingual)-induced vasodilation were studied before and
      after mental stress by high-resolution ultrasound of the radial artery.
      Additionally, FMD was assessed before and 10 to 45 minutes after mental stress
      during intraarterial infusion of a selective endothelin A receptor antagonist (BQ
      123, 1 nmol/min) or saline, respectively. Endothelium-dependent vasodilation was
      reduced by half for about 45 minutes (8.0+/-1.1% versus 4.1+/-1.0%; P<0.002),
      whereas endothelium-independent vasodilation to nitroglycerin remained unaffected
      (15.6+/-1.6 versus 14.3+/-1.3%; NS). Intraarterial infusion of BQ-123, a
      selective endothelin-A receptor antagonist, but not saline prevented the
      impairment of endothelium-dependent vasodilation (8.6+/-1.2 versus 9.4+/-1.3%;
      NS). In contrast, intraarterial infusion of norepinephrine of similar duration as
      mental stress did not inhibit FMD. CONCLUSIONS: Mental stress induces prolonged
      endothelial dysfunction, which is prevented by selective endothelin-A receptor
      antagonism. This represents a novel and important link between mental stress and
      atherosclerotic vascular disease.

PMID- 12070107
TI  - Left atrial appendage activity masquerading as pulmonary vein potentials.
AB  - BACKGROUND: Despite extensive proximal ablation, all potentials frequently cannot
      be eliminated from the left pulmonary veins (PV). Methods and Results- PV
      electrograms were analyzed during sinus rhythm, coronary sinus, and left atrial
      appendage (LAA) pacing, and PV and LAA angiography performed. During pacing, an
      initial low-amplitude slow potential was recorded on the anterior aspect of the
      left superior PV and anticipated with shortest activation time by LAA pacing. Its
      timing coincided with posterior LAA activation, shown to be immediately adjacent
      to the left superior PV by angiography. In the left inferior PV, the first
      potential was smaller and less sharp, coinciding with adjacent low LA activation.
      Angiographically, the LAA was at least 15 mm from the left inferior PV. The
      second sharper potential in both left PVs was eliminated by proximal ablation.
      CONCLUSION: Far field LAA activity consistently adds to PV myocardial
      electrograms in the left superior PV whereas lower, less sharp extravenous
      potentials in the left inferior PV originate from the inferior LA. They can be
      identified by LAA and coronary sinus pacing.

PMID- 12070108
TI  - Mild renal insufficiency is associated with angiographic coronary artery disease
      in women.
AB  - BACKGROUND: Mild renal insufficiency is associated with an increased risk for
      cardiovascular events in women with coronary artery disease (CAD). However, the
      relationship between mild renal insufficiency and atherosclerotic CAD in women is
      not known. Methods and Results- Women with chest pain who were referred for
      coronary angiography in the NHLBI Women's Ischemia Syndrome Evaluation (WISE)
      study underwent quantitative coronary angiography, blood measurements of
      creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty
      six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and
      728 had normal renal function (creatinine <1.2 mg/dL). Creatinine correlated with
      angiographic CAD severity score (r=0.11, P<0.004) and maximum coronary artery
      stenosis (r=0.11, P<0.003). Compared with women with normal renal function, those
      with mild renal insufficiency were more likely to have significant angiographic
      CAD (>/=50% diameter stenosis in >/=1 coronary artery) (61% versus 37%; P<0.001)
      and CAD in multiple vessels (P<0.001 for association) and had greater maximum
      percent diameter coronary stenosis (59+/-35% versus 38+/-36%; P<0.001). Mild
      renal insufficiency was associated with significant angiographic CAD independent
      of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for
      homocysteine in 509 women, mild renal insufficiency remained predictive of CAD
      (OR=3.2, 95%CI=1.4 to 7.2). CONCLUSIONS: In women with chest pain, mild renal
      insufficiency is an independent predictor of significant angiographic CAD. Mildly
      increased serum creatinine is probably a marker for unmeasured proatherogenic
      factors.

PMID- 12070109
TI  - Pharmacological rescue of human K(+) channel long-QT2 mutations: human ether-a-go
      go-related gene rescue without block.
AB  - BACKGROUND: Defective protein trafficking is a consequence of gene mutations.
      Human long-QT (LQT) syndrome results from mutations in several genes, including
      the human ether-a-go-go-related gene (HERG), which encodes a delayed rectifier
      K(+) current. Trafficking-defective mutant HERG protein is a mechanism for
      reduced delayed rectifier K(+) current in LQT2, and high-affinity HERG channel
      blocking drugs can result in pharmacological rescue. Methods and Results- We
      postulated that drug molecules modified to remove high-affinity HERG block may
      still stabilize mutant proteins in a conformation required for rescue. We tested
      terfenadine carboxylate (fexofenadine) and terfenadine, structurally similar
      drugs with markedly different affinities for HERG block, for rescue of
      trafficking-defective LQT2 mutations. Terfenadine rescued the N470D mutation but
      blocked the channels. In contrast, fexofenadine rescued N470D with a half-maximal
      rescue concentration of 177 nmol/L, which is approximately 350-fold lower than
      the half-maximal channel block concentration. The G601S mutation was also rescued
      without channel block. CONCLUSIONS: Pharmacological rescue can occur without
      channel block. This could represent a new antiarrhythmic paradigm in the
      treatment of some trafficking-defective LQT2 mutations.

PMID- 12070110
TI  - Meta-analysis of wine and beer consumption in relation to vascular risk.
AB  - BACKGROUND: Many epidemiological studies have evaluated whether different
      alcoholic beverages protect against cardiovascular disease. We performed a meta
      analysis of 26 studies on the relationship between wine or beer consumption and
      vascular risk. Methods and Results- General variance-based method and fitting
      models were applied to pooled data derived from 26 studies that gave a
      quantitative estimation of the vascular risk associated with either beverage
      consumption. From 13 studies involving 209 418 persons, the relative risk of
      vascular disease associated with wine intake was 0.68 (95% confidence interval,
      0.59 to 0.77) relative to nondrinkers. There was strong evidence from 10 studies
      involving 176 042 persons to support a J-shaped relationship between different
      amounts of wine intake and vascular risk. A statistically significant inverse
      association was found up to a daily intake of 150 mL of wine. The overall
      relative risk of moderate beer consumption, which was measured in 15 studies
      involving 208 036 persons, was 0.78 (95% confidence interval, 0.70 to 0.86).
      However, no significant relationship between different amounts of beer intake and
      vascular risk was found after meta-analyzing 7 studies involving 136 382 persons.
      CONCLUSIONS: These findings show evidence of a significant inverse association
      between light-to-moderate wine consumption and vascular risk. A similar, although
      smaller association was also apparent in beer consumption studies. The latter
      finding, however, is difficult to interpret because no meaningful relationship
      could be found between different amounts of beer intake and vascular risk.

PMID- 12070111
TI  - Transcatheter closure of interatrial communications for secondary prevention of
      paradoxical embolism: single-center experience.
AB  - BACKGROUND: Patients with a patent foramen ovale (PFO) after cerebral, coronary,
      or systemic embolic events of presumed paradoxical origin are at risk for
      recurrent thromboembolism. We report our single-center experience of
      interventional closure of interatrial communications for secondary prevention of
      presumed paradoxical embolism. Methods and Results- Since 1997, percutaneous
      closure of interatrial communications was performed at our institution in 66
      patients (mean age 47.8+/-12.7 years; 31 males) with a PFO or an atrial septal
      defect and at least 1 documented presumed paradoxical thromboembolic event. Fifty
      eight patients had cerebral embolism, 10 had coronary embolism, and 3 had
      peripheral embolism. Several patients experienced multilocal arterial embolism.
      Fifty-four patients had a PFO, 33 of them with an atrial septal aneurysm, and 12
      had an atrial septal defect. The implantation procedure was successful and
      without complication in all patients. After 3 months, only 2 patients showed a
      residual shunt, which disappeared in both cases after 12 months. In 112.2 patient
      years of follow-up (range, 5 weeks to 3.5 years), we have not seen any recurrent
      thromboembolic event. CONCLUSIONS: Interventional closure of interatrial
      communications is a safe and effective therapeutic option for the secondary
      prevention of presumed paradoxical embolism. To further evaluate this strategy,
      randomized trials comparing interventional closure with anticoagulation have been
      initiated by us and others.

PMID- 12070112
TI  - Cardiopulmonary bypass induces release of soluble CD40 ligand.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce platelet activation,
      thrombosis, thrombocytopenia, and a systemic inflammatory response. It is known
      that CD40 ligand (CD40L) exists in platelets, that a soluble form of this protein
      (sCD40L) is released on platelet activation, that platelets are the primary
      source of sCD40L in blood, and that sCD40L is involved in thrombosis and
      inflammation. The present study was designed to determine whether sCD40L is
      released during CPB. Methods and Results- Blood was obtained from patients
      undergoing CPB-requiring surgery and analyzed for sCD40L, interleukin-6, and
      platelet factor 4 and beta-thromboglobulin (markers of platelet activation).
      Platelets were also isolated and analyzed for their levels of CD40L. Plasma
      levels of sCD40L increased >1.7-fold (from 0.29 to 0.51 ng/mL, P=0.001) within 1
      hour on CPB and increased further to 3.7-fold (to 1.08 ng/mL, P=0.03) 2 hours
      after the procedure. Half of the released sCD40L was cleared in 2 hours, which
      allowed the sCD40L to return to approximately baseline levels 8 hours after the
      procedure. The platelet content of CD40L was decreased by 40% (2.675 to 1.64
      ng/10(8) platelets, P=0.001) 1 hour after initiation of CPB and was similar to
      that observed for platelet factor 4 and beta-thromboglobulin. Interleukin-6, a
      marker of inflammation, also increased during CPB. CONCLUSIONS: The present study
      demonstrates that CPB causes an increase in the concentration of plasma sCD40L.
      The corresponding decrease in platelet CD40L suggests that this prothrombotic and
      proinflammatory protein was derived primarily from platelets and may contribute
      to the thrombotic and inflammatory complications associated with CPB.

PMID- 12070113
TI  - Initial clinical experience with the Jarvik 2000 implantable axial-flow left
      ventricular assist system.
AB  - BACKGROUND: Implantable left ventricular assist systems (LVASs) are used for
      bridging to transplantation, bridging to myocardial improvement, and for
      permanent circulatory support. Conventional implantable systems have inherent
      limitations that increase morbidity during support. In contrast, small,
      efficient, axial-flow pumps, which have been under development for the past
      decade, have the potential to improve the length and quality of life in patients
      with severe heart failure. Methods and Results- To assess the safety and clinical
      utility of the Jarvik 2000, we implanted this device in 10 transplant candidates
      (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation
      was achieved through a left thoracotomy during partial cardiopulmonary bypass.
      The mean support period was 84 days. Within 48 hours postoperatively, the cardiac
      index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic
      vascular resistance decreased significantly, and inotropic support became
      unnecessary. Eight patients underwent physical rehabilitation and returned to
      NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and
      pressure-volume loop analyses showed good left ventricular unloading. Seven
      patients underwent transplantation and 3 died during support. No device
      thrombosis was observed at explantation. CONCLUSIONS: The Jarvik 2000 functions
      as a true assist device by partially unloading the left ventricle, thereby
      optimizing the patient's hemodynamics. Our preliminary results indicate that this
      LVAS may safely provide circulatory assistance for heart transplant candidates.

PMID- 12070114
TI  - Home-based intervention in congestive heart failure: long-term implications on
      readmission and survival.
AB  - BACKGROUND: It is not known to what extent initially observed benefits of
      postdischarge programs of care for patients with chronic congestive heart failure
      (CHF) in respect to event-free survival, readmissions, and healthcare costs
      persist in the long term. Methods and Results- We prospectively studied the long
      term effects of a multidisciplinary home-based intervention (HBI) in a cohort of
      CHF patients randomly allocated to either to HBI (n=149) or usual care (n=148).
      During a median of 4.2 years of follow-up, there were significantly fewer primary
      end points (unplanned readmission or death) in the HBI versus usual care group: a
      mean of 0.21 versus 0.37 primary events per patient per month (P<0.01). Median
      event-free survival was more prolonged in the HBI than usual care group (7 versus
      3 months; P<0.01). Fewer HBI patients died (56% versus 65%; P=0.06) and had more
      prolonged survival (a median of 40 versus 22 months; P<0.05) compared with usual
      care. Assignment to HBI was both an independent predictor of event-free survival
      (RR 0.70; P<0.01) and survival alone (RR 0.72; P<0.05). Overall, HBI patients had
      78 fewer unplanned readmissions compared with usual care (0.17 versus 0.29
      readmissions per patient per month; P<0.05). The median cost of these
      readmissions was $A325 versus $A660/month per HBI and usual care patient
      (P<0.01). CONCLUSIONS: The beneficial effects of HBI in reducing frequency of
      unplanned readmissions in CHF patients persist in the long term and are
      associated with prolongation of survival.

PMID- 12070115
TI  - Carvedilol decreases elevated oxidative stress in human failing myocardium.
AB  - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of heart
      failure. However, direct evidence of oxidative stress generation in the human
      failing myocardium has not been obtained. Furthermore, the effect of carvedilol,
      a vasodilating beta-blocker with antioxidant activity, on oxidative stress in
      human failing hearts has not been assessed. This study was therefore designed to
      determine whether levels of lipid peroxides are elevated in myocardia of patients
      with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid
      peroxidation level. Methods and Results- Endomyocardial biopsy samples obtained
      from 23 patients with DCM and 13 control subjects with normal cardiac function
      were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal
      (HNE)-modified protein, which is a major lipid peroxidation product. Expression
      of HNE-modified protein was found in all myocardial biopsy samples from patients
      with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial
      HNE-modified protein levels in patients with DCM were significantly increased
      compared with the levels in control subjects (P<0.0001). Endomyocardial biopsy
      samples from 11 patients with DCM were examined before and after treatment (mean,
      9+/-4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22+/-8 mg/d). After
      treatment with carvedilol, myocardial HNE-modified protein levels decreased by
      40% (P<0.005) along with amelioration of heart failure. CONCLUSIONS: Oxidative
      stress is elevated in myocardia of patients with heart failure. Administration of
      carvedilol resulted in a decrease in the oxidative stress level together with
      amelioration of cardiac function.

PMID- 12070116
TI  - Carotid plaques increase the risk of stroke and subtypes of cerebral infarction
      in asymptomatic elderly: the Rotterdam study.
AB  - BACKGROUND: Few studies have quantified the relation between carotid plaques and
      stroke in asymptomatic patients, and limited data exist on the importance of
      location of plaques or the association with subtypes of cerebral infarction. We
      investigated the relationship between carotid plaques, measured at different
      locations, and risk of stroke and subtypes of cerebral infarction in a population
      based study. Methods and Results- The study was based on the Rotterdam Study and
      included 4217 neurologically asymptomatic subjects aged 55 years or older.
      Presence of carotid plaques at 6 locations in the carotid arteries was assessed
      at baseline. Severity was categorized according to the number of affected sites.
      After a mean follow-up of 5.2 years, 160 strokes had occurred. Data were analyzed
      using Cox proportional hazards regression. Plaques increased the risk of stroke
      and cerebral infarction approximately 1.5-fold, irrespective of plaque location.
      Severe carotid plaques increased the risk of nonlacunar infarction in anterior
      (RR 3.2 [95% CI, 1.1 to 9.7]) but not in posterior circulation (RR 0.6 [95% CI,
      0.1 to 4.9]). A >10-fold increased risk of lacunar infarction was found in
      subjects with severe plaques (RR 10.8 [95% CI, 1.7 to 69.7]). No clear difference
      in risk estimates was seen between ipsilateral and contralateral infarction.
      CONCLUSIONS: Carotid plaques increase the risk of stroke and cerebral infarction,
      irrespective of their location. Plaques increase the risk of infarctions in the
      anterior but not in the posterior circulation. It is likely that carotid plaques
      in neurologically asymptomatic subjects are both markers of generalized
      atherosclerosis and sources of thromboemboli.

PMID- 12070117
TI  - Assessment of coronary function in children with a history of Kawasaki disease
      using (15)O-water positron emission tomography.
AB  - BACKGROUND: Coronary abnormalities after Kawasaki disease (KD) may be associated
      with endothelial dysfunction due to intimal hypertrophy. The purpose of this
      study was to evaluate myocardial flow reserve (MFR) and endothelial function in
      regressed aneurysmal regions after KD. Methods and Results- Subjects were 12
      patients aged 16.0+/-2.6 years who suffered from KD at 1.7+/-1.5 years and 12
      normal subjects aged 26.5+/-3.4 years. MFR and endothelial function were
      estimated, respectively, by changes in myocardial blood flow (MBF) during ATP
      infusion and by that during cold pressor test using (15)O-water positron emission
      tomography. Data from 24 regressed aneurysmal regions were compared with those
      from the corresponding regions (n=36) in the control group. Although the MBF at
      rest in the regressed aneurysmal regions was similar to that in controls, the MBF
      at a hyperemic state induced by ATP infusion in the regressed aneurysmal regions
      was significantly lower than that in the control regions. Therefore, the MFR in
      regressed aneurysmal regions was significantly lower than that in controls
      (3.53+/-0.95 versus 4.60+/-1.14; P<0.05). MBF at rest and during the cold pressor
      test did not change in the control regions, but it was significantly reduced in
      regressed aneurysmal regions. The ratio of MBF during the cold pressor test to
      MBF at rest was significantly lower in regressed aneurysmal regions than in
      control regions (0.67+/-0.15 versus 1.00+/-0.15; P<0.05). CONCLUSIONS: MFR and
      endothelial function are often impaired in regressed aneurysmal regions after KD,
      and tomography enables the noninvasive evaluation of coronary function.

PMID- 12070118
TI  - Ventricular afterload and ventricular work in fontan circulation: comparison with
      normal two-ventricle circulation and single-ventricle circulation with blalock
      taussig shunts.
AB  - BACKGROUND: Recent studies have indicated that there are inherent limitations
      associated with Fontan physiology. However, there have been no quantitative
      analyses of the effects of right heart bypass on ventricular afterload, hydraulic
      power, and resultant overall hemodynamics. Methods and Results- During routine
      cardiac catheterization, aortic impedance and ventricular hydraulic power were
      determined, both at rest and under increased ventricular work induced by
      dobutamine, in 17 patients with Fontan circulation, 15 patients with a single
      ventricle whose pulmonary circulation was maintained only by Blalock-Taussig
      shunts, and 13 patients who had normal 2-ventricle circulation. Both vascular
      resistance (nonpulsatile load on the ventricle) and pulsatile components of
      ventricular afterload (represented by low-frequency impedance) were significantly
      higher in the Fontan group than in the other groups (P<0.01), and this was
      associated with decreased cardiac output in the Fontan patients. In addition,
      hydraulic power cost per unit forward flow was 40% lower in the 2-ventricle
      circulation than in the single-ventricle circulation, suggesting lower
      ventricular efficiency in single-ventricle circulation attributable to the lack
      of a pulmonary ventricle. Furthermore, in the Fontan group, beta-adrenergic
      reserve was markedly decreased because of a limited preload reserve. CONCLUSIONS:
      Fontan physiology is associated with disadvantageous ventricular power and
      afterload profiles and has limited ventricular reserve capacity. Thus, to improve
      the long-term prognosis of patients after Fontan surgery, future research should
      be conducted into medical interventions that can overcome these limitations
      inherent in Fontan circulation.

PMID- 12070119
TI  - Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth
      factor-BB-binding protein and regulates growth factor-induced common postreceptor
      signal in vascular smooth muscle cell.
AB  - BACKGROUND: Vascular smooth muscle cell proliferation plays an important role in
      the development of atherosclerosis. We previously reported that adiponectin, an
      adipocyte-specific plasma protein, accumulated in the human injured artery and
      suppressed endothelial inflammatory response as well as macrophage-to-foam cell
      transformation. The present study investigated the effects of adiponectin on
      proliferation and migration of human aortic smooth muscle cells (HASMCs). Methods
      and Results- HASMC proliferation was estimated by [(3)H] thymidine uptake and
      cell number. Cell migration assay was performed using a Boyden chamber.
      Physiological concentrations of adiponectin significantly suppressed both
      proliferation and migration of HASMCs stimulated with platelet-derived growth
      factor (PDGF)-BB. Adiponectin specifically bound to (125)I-PDGF-BB and
      significantly inhibited the association of (125)I-PDGF-BB with HASMCs, but no
      effects were observed on the binding of (125)I-PDGF-AA or (125)I-heparin-binding
      epidermal growth factor (EGF)-like growth factor (HB-EGF) to HASMCs. Adiponectin
      strongly and dose-dependently suppressed PDGF-BB-induced p42/44 extracellular
      signal-related kinase (ERK) phosphorylation and PDGF beta-receptor
      autophosphorylation analyzed by immunoblot. Adiponectin also reduced PDGF-AA
      stimulated or HB-EGF-stimulated ERK phosphorylation in a dose-dependent manner
      without affecting autophosphorylation of PDGF alpha-receptor or EGF receptor.
      CONCLUSIONS: The adipocyte-derived plasma protein adiponectin strongly suppressed
      HASMC proliferation and migration through direct binding with PDGF-BB and
      generally inhibited growth factor-stimulated ERK signal in HASMCs, suggesting
      that adiponectin acts as a modulator for vascular remodeling.

PMID- 12070120
TI  - Cytosolic heat shock protein 60, apoptosis, and myocardial injury.
AB  - BACKGROUND: Heat shock proteins (HSPs) are well known for their ability to
      "protect" the structure and function of native macromolecules, particularly as
      they traffic across membranes. Considering the role of key mitochondrial proteins
      in apoptosis and the known antiapoptotic effects of HSP27 and HSP72, we
      postulated that HSP60, primarily a mitochondrial protein, also exerts an
      antiapoptotic effect. Methods and Results- To test this hypothesis, we used an
      antisense phosphorothioate oligonucleotide to effect a 50% reduction in the
      levels of HSP60 in cardiac myocytes, a cell type that has abundant mitochondria.
      The induced decrease in HSP60 precipitated apoptosis, as manifested by the
      release of cytochrome c, activation of caspase 3, and induction of DNA
      fragmentation. Antisense treatment was associated with an increase in bax and a
      decrease in bcl-2 secondary to increased synthesis of bax and degradation of bcl
      2. A control oligonucleotide had no effect on these measurements. We further
      demonstrated that cytosolic HSP60 forms a macromolecular complex with bax and bak
      in vitro suggesting that complex formation with HSP60 may block the ability of
      bax and bak to effect apoptosis in vivo. Lastly, we show that as cytosolic
      (nonmitochondrial) HSP60 decreases, a small unbound fraction of bax appears and
      that the amount of bax associated with the mitochondria and cell membranes
      increases. CONCLUSIONS: These results support a key antiapoptotic role for
      cytosolic HSP60. To our knowledge, this is the first report suggesting that
      interactions of HSP60 with bax and/or bak regulate apoptosis.

PMID- 12070121
TI  - Essential role of monocyte chemoattractant protein-1 in development of restenotic
      changes (neointimal hyperplasia and constrictive remodeling) after balloon
      angioplasty in hypercholesterolemic rabbits.
AB  - BACKGROUND: Renarrowing of dilated arterial sites (restenosis) hampers the
      clinical benefits of coronary angioplasty. Infiltration and activation of
      monocytes in the arterial wall mediated by monocyte chemoattractant protein-1
      (MCP-1) might be a major cause of restenosis after angioplasty. However, there is
      no direct evidence to support a definite role of MCP-1 in the development of
      restenosis. Methods and Results- We recently devised a new strategy for anti-MCP
      1 gene therapy by transfecting an N-terminal deletion mutant of the MCP-1 gene
      into skeletal muscles. We used this strategy to investigate the role of MCP-1 in
      the development of restenotic changes after balloon injury in the carotid artery
      in hypercholesterolemic rabbits. Intramuscular transfection of the mutant MCP-1
      gene suppressed monocyte infiltration/activation in the injured arterial wall and
      thus attenuated the development of neointimal hyperplasia and negative
      remodeling. CONCLUSIONS: MCP-1-mediated monocyte infiltration is necessary in the
      development of restenotic changes to balloon injury in hypercholesterolemic
      rabbits. This strategy may be a useful and practical form of gene therapy against
      human restenosis.

PMID- 12070122
TI  - Overexpression of a constitutively active protein kinase G mutant reduces
      neointima formation and in-stent restenosis.
AB  - BACKGROUND: Neointima formation after arterial injury is associated with reduced
      vascular cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase
      (PKG), a major cGMP effector in vascular smooth muscle. We tested the effect of
      PKG overexpression on the neointimal response to vascular injury. Methods and
      Results- Infection of cultured rat aortic smooth muscle cells (RASMCs) with an
      adenoviral vector specifying a cGMP-independent, constitutively active PKG mutant
      (AdPKGcat) reduced serum-induced migration by 33% and increased serum-deprivation
      induced apoptosis 2-fold (P<0.05 for both). Infection with wild-type PKG (AdPKG),
      in the absence of cGMP, did not affect migration or apoptosis. Two weeks after
      balloon-injured rat carotid arteries were infected with 1x 10(10) pfu AdPKGcat
      (n=12), AdPKG (n=8), or a control adenovirus (n=8), intima-to-media ratio was
      less in AdPKGcat-infected arteries than in AdPKG- or control adenovirus-infected
      vessels (0.26+/-0.06 versus 0.61+/-0.12 and 0.70+/-0.12, respectively, P<0.05 for
      both). Two weeks after intramural administration of 1.75x10(10) pfu AdPKGcat
      (n=8) or a control adenovirus (n=8) into porcine coronary arteries with in-stent
      restenosis, luminal diameter was greater in AdPKGcat-infected arteries than in
      control adenovirus-infected vessels (2.32+/-0.16 versus 1.81+/-0.13 mm, P=0.028),
      associated with reduced neointimal area (3.30+/-0.24 versus 4.15+/-0.13 mm(2),
      P=0.008), neointima-to-vessel area ratio (0.42+/-0.05 versus 0.58+/-0.04,
      P<0.05), and percent stenosis (45+/-6% versus 70+/-4%, P<0.05). CONCLUSIONS:
      Expression of a constitutively active PKG reduces neointima formation after
      balloon injury in rats and reduces coronary in-stent restenosis in pigs. PKGcat
      gene transfer may be a promising strategy for vasculoproliferative disorders.

PMID- 12070124
TI  - Report of the National Heart, Lung, and Blood Institute-National Institute of
      Diabetes and Digestive and Kidney Diseases Working Group on the pathophysiology
      of obesity-associated cardiovascular disease.

PMID- 12070123
TI  - Systemic inflammation induced by lipopolysaccharide increases neointimal
      formation after balloon and stent injury in rabbits.
AB  - BACKGROUND: Emerging data indicate that the inflammatory response after
      mechanical arterial injury correlates with the severity of neointimal hyperplasia
      in animal models and postangioplasty restenosis in humans. The present study was
      designed to examine whether a nonspecific stimulation of the innate immune
      system, induced in close temporal proximity to the vascular injury, would
      modulate the results of the procedure. Methods and Results- Rabbits subjected to
      iliac artery balloon injury (balloon denudation with or without stent deployment)
      were injected twice with a bacterial lipopolysaccharide (LPS) (500 ng/rabbit)
      before and after surgery. The dose was chosen to be sufficient to induce systemic
      inflammation but not septic shock. A systemic marker of inflammation (serum
      interleukin-1beta levels measured by ELISA) and monocytic stimulation (CD14
      levels on monocytes measured by flow cytometry) were increased after LPS
      administration. Arterial macrophage infiltration at 7 days after injury was 1.7+/
      1.2% of total cells in controls and 4.2+/-1.8% in LPS-treated rabbits (n=4,
      P<0.05). Morphometric analysis of the injured arteries 4 weeks after injury
      revealed significantly increased luminal stenosis (38+/-4.2% versus 23+/-2.6,
      mean+/- SEM; n=8, P<0.05) and neointima-to-media ratio (1.26+/-0.21 versus 0.66+/
      0.09, P<0.05) in LPS-treated animals compared with controls. This effect was
      abolished by anti-CD14 Ab administration. Serum interleukin-1beta levels and
      monocyte CD14 expression were significantly increased in correlation with the
      severity of intimal hyperplasia. LPS treatment increased neointimal area after
      stenting from 0.57+/-0.07 to 0.77+/- 0.1 mm(2) and stenosis from 9+/-1% to 13+/
      1.7% (n=5, P< 0.05). CONCLUSIONS: Nonspecific systemic stimulation of the innate
      immune system concurrently with arterial vascular injury facilitates neointimal
      formation, and conditions associated with increased inflammation may increase
      restenosis.

PMID- 12070125
TI  - Images in cardiovascular medicine. Aortic allograft in the pulmonary position
      after twenty-three years.

PMID- 12070126
TI  - Images in cardiovascular medicine. Prenatal diagnosis of aortopulmonary window by
      fetal echocardiography.

PMID- 12070128
TI  - Human securin proteolysis is controlled by the spindle checkpoint and reveals
      when the APC/C switches from activation by Cdc20 to Cdh1.
AB  - Progress through mitosis is controlled by the sequential destruction of key
      regulators including the mitotic cyclins and securin, an inhibitor of anaphase
      whose destruction is required for sister chromatid separation. Here we have used
      live cell imaging to determine the exact time when human securin is degraded in
      mitosis. We show that the timing of securin destruction is set by the spindle
      checkpoint; securin destruction begins at metaphase once the checkpoint is
      satisfied. Furthermore, reimposing the checkpoint rapidly inactivates securin
      destruction. Thus, securin and cyclin B1 destruction have very similar
      properties. Moreover, we find that both cyclin B1 and securin have to be degraded
      before sister chromatids can separate. A mutant form of securin that lacks its
      destruction box (D-box) is still degraded in mitosis, but now this is in
      anaphase. This destruction requires a KEN box in the NH2 terminus of securin and
      may indicate the time in mitosis when ubiquitination switches from APCCdc20 to
      APCCdh1. Lastly, a D-box mutant of securin that cannot be degraded in metaphase
      inhibits sister chromatid separation, generating a cut phenotype where one cell
      can inherit both copies of the genome. Thus, defects in securin destruction alter
      chromosome segregation and may be relevant to the development of aneuploidy in
      cancer.

PMID- 12070129
TI  - Differential PI 3-kinase dependence of early and late phases of recycling of the
      internalized AT1 angiotensin receptor.
AB  - Agonist-induced endocytosis and processing of the G protein-coupled AT1
      angiotensin II (Ang II) receptor (AT1R) was studied in HEK 293 cells expressing
      green fluorescent protein (GFP)- or hemagglutinin epitope-tagged forms of the
      receptor. After stimulation with Ang II, the receptor and its ligand colocalized
      with Rab5-GFP and Rab4-GFP in early endosomes, and subsequently with Rab11-GFP in
      pericentriolar recycling endosomes. Inhibition of phosphatidylinositol (PI) 3
      kinase by wortmannin (WT) or LY294002 caused the formation of large endosomal
      vesicles of heterogeneous Rab composition, containing the ligand-receptor complex
      in their limiting membranes and in small associated vesicular structures. In
      contrast to Alexa(R)-transferrin, which was mainly found in small vesicles
      associated with the outside of large vesicles in WT-treated cells, rhodamine-Ang
      II was also segregated into small internal vesicles. In cells labeled with 125I
      Ang II, WT treatment did not impair the rate of receptor endocytosis, but
      significantly reduced the initial phase of receptor recycling without affecting
      its slow component. Similarly, WT inhibited the early, but not the slow,
      component of the recovery of AT1R at the cell surface after termination of Ang II
      stimulation. These data indicate that internalized AT1 receptors are processed
      via vesicles that resemble multivesicular bodies, and recycle to the cell surface
      by a rapid PI 3-kinase-dependent recycling route, as well as by a slower pathway
      that is less sensitive to PI 3-kinase inhibitors.

PMID- 12070130
TI  - Functional binding interaction identified between the axonal CAM L1 and members
      of the ERM family.
AB  - A yeast two-hybrid library was screened using the cytoplasmic domain of the
      axonal cell adhesion molecule L1 to identify binding partners that may be
      involved in the regulation of L1 function. The intracellular domain of L1 bound
      to ezrin, a member of the ezrin, radixin, and moesin (ERM) family of membrane
      cytoskeleton linking proteins, at a site overlapping that for AP2, a clathrin
      adaptor. Binding of bacterial fusion proteins confirmed this interaction. To
      determine whether ERM proteins interact with L1 in vivo, extracellular antibodies
      to L1 were used to force cluster the protein on cultured hippocampal neurons and
      PC12 cells, which were then immunolabeled for ERM proteins. Confocal analysis
      revealed a precise pattern of codistribution between ERMs and L1 clusters in
      axons and PC12 neurites, whereas ERMs in dendrites and spectrin labeling remained
      evenly distributed. Transfection of hippocampal neurons grown on an L1 substrate
      with a dominant negative ERM construct resulted in extensive and abnormal
      elaboration of membrane protrusions and an increase in axon branching,
      highlighting the importance of the ERM-actin interaction in axon development.
      Together, our data indicate that L1 binds directly to members of the ERM family
      and suggest this association may coordinate aspects of axonal morphogenesis.

PMID- 12070131
TI  - Modulation of receptor cycling by neuron-enriched endosomal protein of 21 kD.
AB  - Although correct cycling of neuronal membrane proteins is essential for neurite
      outgrowth and synaptic plasticity, neuron-specific proteins of the implicated
      endosomes have not been characterized. Here we show that a previously cloned,
      developmentally regulated, neuronal protein of unknown function binds to syntaxin
      13. We propose to name this protein neuron-enriched endosomal protein of 21 kD
      (NEEP21), because it is colocalized with transferrin receptors, internalized
      transferrin (Tf), and Rab4. In PC12 cells, NEEP21 overexpression accelerates Tf
      internalization and recycling, whereas its down-regulation strongly delays Tf
      recycling. In primary neurons, NEEP21 is localized to the somatodendritic
      compartment, and, upon N-methyl-d-aspartate (NMDA) stimulation, the alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate receptor subunit GluR2 is internalized
      into NEEP21-positive endosomes. NEEP21 down-regulation retards recycling of GluR1
      to the cell surface after NMDA stimulation of hippocampal neurons. In summary,
      NEEP21 is a neuronal protein that is localized to the early endosomal pathway and
      is necessary for correct receptor recycling in neurons.

PMID- 12070133
TI  - The thrombin mutant W215A/E217A shows safe and potent anticoagulant and
      antithrombotic effects in vivo.
AB  - Administration of the thrombin mutant W215A/E217A (WE), rationally designed for
      selective activation of the anticoagulant protein C, elicits safe and potent
      anticoagulant and antithrombotic effects in a baboon model of platelet-dependent
      thrombosis. The lowest dose of WE tested (0.011 mg/kg bolus) reduced platelet
      thrombus accumulation by 80% and was at least as effective as the direct
      administration of 40-fold more (0.45 mg/kg bolus) activated protein C. WE-treated
      animals showed no detectable hemorrhage or organ failure. No procoagulant
      activity could be detected for up to 1 week in baboon plasma obtained following
      WE administration. These results show that engineered thrombin derivatives that
      selectively activate protein C may represent useful therapeutic agents for the
      treatment of thrombotic disorders.

PMID- 12070134
TI  - Introduction of the most common cystic fibrosis mutation (Delta F508) into human
      P-glycoprotein disrupts packing of the transmembrane segments.
AB  - The most common mutation in cystic fibrosis (deletion of phenylalanine 508
      (DeltaF508) in the cystic fibrosis conductance transmembrane regulator (CFTR)
      gene) causes defective synthesis of CFTR protein. To understand how this deletion
      interferes with protein folding, we made the equivalent deletion (DeltaY490) in P
      glycoprotein (P-gp). A Cys-less P-gp with cysteines in transmembrane (TM) 4 or
      TM5 can be cross-linked with a cysteine in TM12. Deleting Tyr(490) in P-gp
      resulted in an inactive and defectively processed mutant in which no cross
      linking between TM4 or TM5 and TM12 was detected. Expression of the DeltaY490
      mutant in the presence of a chemical chaperone corrected the processing defect
      and yielded active P-gp mutants that could be cross-linked between TM4 or TM5 and
      TM12. Cross-linking between TM4 or TM5 and TM12 was also detected when residues
      (483)TIAENIRYG(491) in P-gp were replaced with residues (501)TIKENIIFG(509) from
      CFTR (P-gp/CFTR). Deleting Phe(508) in the P-gp/CFTR chimera, however, caused
      defective processing of the mutant protein and no detectable cross-linking
      between TM4 or TM5 and TM12. The processing defect was corrected with a chemical
      chaperone and yielded active P-gp/CFTR mutant proteins that could be cross
      linked. These results show that deletion at residue 490 disrupts packing of the
      TM segments possibly by affecting interaction between the first nucleotide
      binding domain (Tyr(490)) and the first cytoplasmic loop (Glu(184)).

PMID- 12070132
TI  - Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by
      distinct NSF activities drives Golgi membrane fusion.
AB  - Characterization of mammalian NSF (G274E) and Drosophila NSF (comatose) mutants
      revealed an evolutionarily conserved NSF activity distinct from ATPase-dependent
      SNARE disassembly that was essential for Golgi membrane fusion. Analysis of
      mammalian NSF function during cell-free assembly of Golgi cisternae from mitotic
      Golgi fragments revealed that NSF disassembles Golgi SNAREs during mitotic Golgi
      fragmentation. A subsequent ATPase-independent NSF activity restricted to the
      reassembly phase is essential for membrane fusion. NSF/alpha-SNAP catalyze the
      binding of GATE-16 to GOS-28, a Golgi v-SNARE, in a manner that requires ATP but
      not ATP hydrolysis. GATE-16 is essential for NSF-driven Golgi reassembly and
      precludes GOS-28 from binding to its cognate t-SNARE, syntaxin-5. We suggest that
      this occurs at the inception of Golgi reassembly to protect the v-SNARE and
      regulate SNARE function.

PMID- 12070135
TI  - JAM2 interacts with alpha4beta1. Facilitation by JAM3.
AB  - We have previously reported that junctional adhesion molecule 2 (JAM2) adheres to
      T cells through heterotypic interactions with JAM3. An examination of the cation
      dependence of JAM2 adhesion to HSB cells revealed a Mn(2+)-enhanced binding
      component indicative of integrin involvement. Using neutralizing integrin
      antibodies, we have defined an interaction between JAM2 and alpha(4)beta(1) in T
      cells. The interaction is readily amenable to drug intervention as demonstrated
      by the ability of TBC 772, an alpha(4)-specific inhibitor, to attenuate the
      Mn(2+)-enhanced component. Intriguingly, the engagement of alpha(4)beta(1) by
      JAM2 is only enabled following prior adhesion of JAM2 with JAM3 and is not
      detectable in cells where JAM3 expression is absent. Supporting this observation,
      we show that neutralizing JAM3 serum and soluble JAM3 ectodomain inhibit not only
      JAM2 binding to JAM3 but also prevent JAM2/alpha(4)beta(1) interactions in T
      cells. We further define the first Ig-like fold of JAM2 as being competent in
      binding both JAM3 and alpha(4)beta(1) counter-receptors. Mutagenesis of the only
      acidic residue in the C-D loop of this Ig fold, namely Asp-82, has no bearing on
      alpha(4)beta(1) interactions, and thus JAM2 deviates somewhat from the mechanism
      used by other immunoglobulin superfamily cell adhesion molecules to engage
      integrin.

PMID- 12070136
TI  - Methylation of histone H3 by COMPASS requires ubiquitination of histone H2B by
      Rad6.
AB  - The DNA of eukaryotes is wrapped around nucleosomes and packaged into chromatin.
      Covalent modifications of the histone proteins that comprise the nucleosome alter
      chromatin structure and have major effects on gene expression. Methylation of
      lysine 4 of histone H3 by COMPASS is required for silencing of genes located near
      chromosome telomeres and within the rDNA (Krogan, N. J, Dover, J., Khorrami, S.,
      Greenblatt, J. F., Schneider, J., Johnston, M., and Shilatifard, A. (2002) J.
      Biol. Chem. 277, 10753-10755; Briggs, S. D., Bryk, M., Strahl, B. D., Cheung, W.
      L., Davie, J. K., Dent, S. Y., Winston, F., and Allis, C. D. (2001) Genes. Dev.
      15, 3286-3295). To learn about the mechanism of histone methylation, we surveyed
      the genome of the yeast Saccharomyces cerevisiae for genes necessary for this
      process. By analyzing approximately 4800 mutant strains, each deleted for a
      different non-essential gene, we discovered that the ubiquitin-conjugating enzyme
      Rad6 is required for methylation of lysine 4 of histone H3. Ubiquitination of
      histone H2B on lysine 123 is the signal for the methylation of histone H3, which
      leads to silencing of genes located near telomeres.

PMID- 12070137
TI  - Insulin-like growth factor-1-mediated AKT activation postpones the onset of
      ultraviolet B-induced apoptosis, providing more time for cyclobutane thymine
      dimer removal in primary human keratinocytes.
AB  - Insulin-like growth factor-1 (IGF-1) acts as a potent survival factor in numerous
      cell lines, primarily through activation of the AKT signaling pathway. Although
      some targets of this pathway have known anti-apoptotic functions, its
      relationship with the improved survival of cells after exposure to environmental
      stresses, including UVB, remains largely unclear. We report that in growth factor
      deprived keratinocytes, IGF-1 significantly and consistently delayed the onset of
      UVB-induced apoptosis by >7 h. This delay allowed IGF-1-supplemented
      keratinocytes to repair significantly more cyclobutane thymine dimers than their
      growth factor-deprived counterparts. This increase in cyclobutane thymine removal
      resulted in enhanced survival if the amount of DNA damage was not too high. To
      increase cell survival after UVB irradiation, IGF-1 supplementation was required
      only during this initial time period in which extra repair was executed. Finally,
      we show that IGF-1 mediated this delay in the onset of UVB-induced apoptosis
      through activation of the AKT signaling pathway. We therefore believe that the
      AKT signaling pathway increases cell survival after a genotoxic insult such as
      UVB irradiation not by inhibiting the apoptotic stimulus, but only by postponing
      the induction of apoptosis, giving the DNA repair mechanism more time to work.

PMID- 12070138
TI  - Regulated translation of heparan sulfate N-acetylglucosamine N-deacetylase/n
      sulfotransferase isozymes by structured 5'-untranslated regions and internal
      ribosome entry sites.
AB  - We report the full-length 5'-untranslated region (5'-UTR) sequences of the four
      vertebrate heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferases
      (NDSTs) and their role in translational regulation in vivo and in vitro. All four
      NDST 5'-UTR sequences are unusually long, have a high degree of predicted
      secondary structure, and contain multiple upstream AUG codons, which together
      impose a major barrier to conventional, cap-dependent ribosomal scanning. At
      least two alternatively spliced forms of NDST2 differing in their 5'-UTRs exist,
      and two forms of NDST4 arise from alternative transcriptional start sites. The 5'
      UTRs do not show any significant sequence similarity between isozymes, but
      possess highly conserved regions between mouse and human orthologs, pointing
      toward evolutionarily conserved functions. Expression of bicistronic vector
      constructs showed that the 5'-UTRs of NDST1-4 are capable of regulating
      translation differentially in vivo dependent on cell type and culture conditions.
      In vitro translation of a reporter gene located downstream of the UTRs
      demonstrated the presence of internal ribosome entry sites, providing an
      additional, cap-independent step in fine-tuning NDST expression. Comparative
      studies of NDST1-3 mRNAs and protein expression in brain and embryonic extracts
      revealed striking differences in translational efficiency. Other genes necessary
      for glycosaminoglycan synthesis in addition to the NDST isozymes have long,
      structured 5'-UTRs. Because several growth factors and morphogens that bind
      heparan sulfate also contain structured 5'-UTRs, translational regulation may
      coordinate the action of these factors and their heparan sulfate co-receptors.

PMID- 12070139
TI  - MLN64 mediates mobilization of lysosomal cholesterol to steroidogenic
      mitochondria.
AB  - This study demonstrates that the steroidogenic acute regulatory protein-related
      lipid transfer (START) domain-containing protein, MLN64, participates in
      intracellular cholesterol trafficking. Analysis of the intracellular itinerary of
      MLN64 and MLN64 mutants tagged with green fluorescent protein showed that the N
      terminal transmembrane domains mediate endocytosis of MLN64 from the plasma
      membrane to late endocytic compartments. MLN64 constitutively traffics via
      dynamic NPC1-containing late endosomal tubules in normal cells; this dynamic
      movement was inhibited in cholesterol-loaded cells, and MLN64 is trapped at the
      periphery of cholesterol-laden lysosomes. The MLN64 START domain stimulated free
      cholesterol transfer from donor to acceptor mitochondrial membranes and enhanced
      steroidogenesis by placental mitochondria. Expression of a truncated form of
      MLN64 (DeltaSTART-MLN64), which contains N-terminal transmembrane domains but
      lacks the START domain, caused free cholesterol accumulation in lysosomes and
      inhibited late endocytic dynamics. The DeltaSTART-MLN64 dominant negative protein
      was located at the surface of the cholesterol-laden lysosomes. This dominant
      negative mutant suppressed steroidogenesis in COS cells expressing the
      mitochondrial cholesterol side chain cleavage system. We conclude that MLN64
      participates in mobilization and utilization of lysosomal cholesterol by virtue
      of the START domain's role in cholesterol transport.

PMID- 12070140
TI  - Vanadate-induced expression of hypoxia-inducible factor 1 alpha and vascular
      endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and
      reactive oxygen species.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix
      transcription factor composed of HIF-1 alpha and HIF-1 beta/aryl hydrocarbon
      nuclear translocator subunits. HIF-1 expression is induced by hypoxia, growth
      factors, and activation of oncogenes. In response to hypoxia, HIF-1 activates the
      expression of many genes including vascular endothelial growth factor (VEGF) and
      erythropoietin. HIF-1 and VEGF play an important role in angiogenesis and tumor
      progression. Vanadate is widely used in industry, and is a potent inducer of
      tumors in humans and animals. In this study, we demonstrate that vanadate induces
      HIF-1 activity through the expression of HIF-1alpha but not HIF-1 beta subunit,
      and increases VEGF expression in DU145 human prostate carcinoma cells. We also
      studied the signaling pathway involved in vanadate-induced HIF-1 alpha and VEGF
      expression and found that phosphatidylinositol 3-kinase/Akt signaling was
      required for HIF-1 and VEGF expression induced by vanadate, whereas mitogen
      activated protein kinase pathway was not required. We also found that reactive
      oxygen species (ROS) were involved in vanadate-induced expression of HIF-1 and
      VEGF in DU145 cells. The major species of ROS responsible for the induction of
      HIF-1 and VEGF expression was H(2)O(2). These results suggest that the expression
      of HIF-1 and VEGF induced by vanadate through PI3K/Akt may be an important
      signaling pathway in the vanadate-induced carcinogenesis, and ROS may play an
      important role.

PMID- 12070141
TI  - Hypochlorite-modified high density lipoprotein, a high affinity ligand to
      scavenger receptor class B, type I, impairs high density lipoprotein-dependent
      selective lipid uptake and reverse cholesterol transport.
AB  - Hypochlorous acid/hypochlorite (HOCl/OCl(-)), a potent oxidant generated in vivo
      by the myeloperoxidase-H(2)O(2)-chloride system of activated phagocytes, alters
      the physiological properties of high density lipoprotein (HDL) by generating a
      proatherogenic lipoprotein particle. On endothelial cells lectin-like oxidized
      low density lipoprotein receptor 1 (LOX-1) and scavenger receptor class B, type I
      (SR-BI), act in concert by mediating the holoparticle of and selective
      cholesteryl ester uptake from HOCl-HDL. We therefore investigated the ligand
      specificity of HOCl-HDL to SR-BI-overexpressing Chinese hamster ovary cells.
      Binding of HOCl-HDL was saturable, and the degree of HOCl modification was the
      determining factor for increased binding affinity to SR-BI. Competition
      experiments further confirmed that HOCl-HDL binds with increased affinity to the
      same or overlapping domain(s) of SR-BI as does native HDL. Furthermore, SR-BI
      mediated selective HDL-cholesteryl ester association as well as time- and
      concentration-dependent cholesterol efflux from SR-BI overexpressing Chinese
      hamster ovary cells were, depending on the degree of HOCl modification of HDL,
      markedly impaired. The most significant findings of this study were that the
      presence of very low concentrations of HOCl-HDL severely impaired SR-BI-mediated
      bidirectional cholesterol flux mediated by native HDL. The colocalization of
      immunoreactive HOCl-modified epitopes with apolipoprotein A-I along with deposits
      of lipids in serial sections of human atheroma shown here indicates that the
      myeloperoxidase-H(2)O(2)-halide system contributes to oxidative damage of HDL in
      vivo.

PMID- 12070143
TI  - Non-steroidal anti-inflammatory drugs stimulate secretion of non-amyloidogenic
      precursor protein.
AB  - Chronic inflammatory processes are associated with the pathophysiology of
      Alzheimer's disease (AD), and it has been proposed that treatment with non
      steroidal anti-inflammatory drugs (NSAIDs) reduces the risk for AD. Here we
      report that various NSAIDs, such as the cyclooxygenase inhibitors, nimesulide,
      ibuprofen and indomethacin, as well as thalidomide (Thal) and its non-teratogenic
      analogue, supidimide, significantly stimulated the secretion of the non
      amyloidogenic alpha-secretase form of the soluble amyloid precursor protein (sAPP
      alpha) into the conditioned media of SH-SY5Y neuroblastoma and PC12 cells. These
      NSAIDs markedly reduced the levels of the cellular APP holoprotein, further
      accelerating non-amyloidogenic processes. sAPP alpha release, induced by
      nimesulide and Thal, was modulated by inhibitors of protein kinase C and Erk
      mitogen-activated protein (MAP) kinase. Furthermore, in results complementary to
      the inhibitor studies, we show for the first time that NSAIDs can activate the
      Erk MAP kinase signaling cascade, thus identifying a novel pharmacology mechanism
      of NSAIDs. Our findings suggest that NSAIDs and Thal might prove useful to favor
      non-amyloidogenic APP processing by enhancing alpha-secretase activity, thereby
      reducing the formation of amyloidogenic derivatives, and therefore are of
      potential therapeutic value in AD.

PMID- 12070142
TI  - Fasting and postprandial overproduction of intestinally derived lipoproteins in
      an animal model of insulin resistance. Evidence that chronic fructose feeding in
      the hamster is accompanied by enhanced intestinal de novo lipogenesis and ApoB48
      containing lipoprotein overproduction.
AB  - Insulin-resistant states are characterized by hypertriglyceridemia, predominantly
      because of overproduction of hepatic very low density lipoprotein particles. The
      additional contribution of intestinal lipoprotein overproduction to the
      dyslipidemia of insulin-resistant states has not been previously appreciated.
      Here, we have investigated intestinal lipoprotein production in a fructose-fed
      hamster model of insulin resistance previously documented to have whole body and
      hepatic insulin resistance, and hepatic very low density lipoprotein
      overproduction. Chronic fructose feeding for 3 weeks induced significant
      oversecretion of apolipoprotein B48 (apoB48)-containing lipoproteins in the
      fasting state and during steady state fat feeding, based on (a) in vivo Triton
      WR1339 studies of apoB48 production as well as (b) ex vivo pulse-chase labeling
      of intestinal enterocytes from fasted and fed hamsters. ApoB48 particle
      overproduction was accompanied by increased intracellular apoB48 stability,
      enhanced lipid synthesis, higher abundance of microsomal triglyceride transfer
      protein mass, and a significant shift toward the secretion of larger chylomicron
      like particles. ApoB48 particle overproduction was not observed with short-term
      fructose feeding or in vitro incubation of enterocytes with fructose. Secretion
      of intestinal apoB48 and triglyceride was closely linked to intestinal enterocyte
      de novo lipogenesis, which was up-regulated in fructose-fed hamsters. Inhibition
      of fatty acid synthesis by cerulenin, a fatty acid synthase inhibitor, resulted
      in a dose-dependent decrease in intestinal apoB48 secretion. Overall, these
      findings further suggest that intestinal overproduction of apoB48 lipoproteins
      should also be considered as a major contributor to the fasting and postprandial
      dyslipidemia observed in response to chronic fructose feeding and development of
      an insulin-resistant state.

PMID- 12070144
TI  - A procedure for detection and quantitation of cavity volumes proteins.
      Application to measure the strength of the hydrophobic driving force in protein
      folding.
AB  - Accurate identification of cavities is important in the study of protein
      structure, stability, design, and ligand binding. Identification and quantitation
      of cavities is a nontrivial problem because most cavities are connected to the
      protein exterior. We describe a computational procedure for quantitating cavity
      volumes and apply this to derive an estimate of the hydrophobic driving force in
      protein folding. A grid-based Monte Carlo procedure is used to position water
      molecules on the surface of a protein. A Voronoi procedure is used to identify
      and quantitate empty space within the solvated protein. Additional cavities not
      detected by other existing procedures can be identified. Most of these are close
      to surface concavities. Residue volumes for both the interior and the surface
      residues as well as cavity volumes are in good agreement with volumes calculated
      from fully hydrated protein structures obtained from molecular dynamic
      simulations. We show that the loss of stability because of cavity-creating
      mutations correlates better with cavity volumes determined by this procedure than
      with cavity volumes determined by other methods. Available structural and
      thermodynamic data for a number of cavity-containing mutants were analyzed to
      obtain estimates of 26.1 cal x mol(-1) x A(-3) and 18.5 cal x mol(-1) x A(-2) for
      the relative contributions of cavity formation and the hydrophobic effect to the
      observed stability changes. The present estimate for the hydrophobic driving
      force is at the lower end of estimates derived from model compound studies and
      considerably lower than previous estimates of approximately 50 cal x mol(-1) x A(
      2) derived from protein mutational data. In the absence of structural
      rearrangement, on average, deletion of a single methylene group is expected to
      result in losses in stability of 0.41 and 0.70 kcal x mol(-1) resulting from
      decrease in hydrophobicity and packing, respectively.

PMID- 12070145
TI  - Overexpression of apolipoprotein A-IV enhances lipid transport in newborn swine
      intestinal epithelial cells.
AB  - Apolipoprotein A-IV (apoA-IV) has myriad functions, including roles as a post
      prandial satiety factor and lipid antioxidant. ApoA-IV is expressed in mammalian
      small intestine and is up-regulated in response to lipid absorption. In newborn
      swine jejunum, a high fat diet acutely induces a 7-fold increase in apoA-IV
      expression. To determine whether apoA-IV plays a role in the transport of
      absorbed lipid, swine apoA-IV was overexpressed in a newborn swine enterocyte
      cell line, IPEC-1, followed by analysis of the expression of genes related to
      lipoprotein assembly and lipid transport, as well as quantitation of lipid
      synthesis and secretion. A full-length swine apoA-IV cDNA was cloned, sequenced,
      and inserted into a Vp and Rep gene-deficient adeno-associated viral vector,
      containing the cytomegalovirus immediate early promoter/enhancer and neomycin
      resistance gene, and was used to transfect IPEC-1 cells. Control cells were
      transfected with the same vector minus the apoA-IV insert. Using neomycin
      selection, apoA-IV-overexpressing (+AIV) and control (-AIV) clones were isolated
      for further study. Both undifferentiated (-D) and differentiated (+D) +AIV cells
      expressed 40- to 50-fold higher levels of apoA-IV mRNA and both intracellular and
      secreted apoA-IV protein compared with -AIV cells. Expression of other genes was
      not affected by apoA-IV overexpression in a manner that would contribute to
      enhanced lipid secretion. +D +AIV cells secreted 4.9-fold more labeled
      triacylglycerol (TG), 4.6-fold more labeled cholesteryl ester (CE), and 2-fold
      more labeled phospholipid (PL) as lipoproteins, mostly in the chylomicron/very
      low density lipoprotein (VLDL) density range. ApoA-IV overexpression in IPEC-1
      cells enhances basolateral TG, CE, and PL secretion in chylomicron/VLDL
      particles. This enhancement is not associated with up-regulation of other genes
      involved in lipid transport. ApoA-IV may play a role in facilitating enterocyte
      lipid transport, particularly in the neonate receiving a diet of high fat breast
      milk.

PMID- 12070146
TI  - The adenovirus E1A protein targets the SAGA but not the ADA transcriptional
      regulatory complex through multiple independent domains.
AB  - Expression of the adenovirus E1A protein in the simple eukaryote Saccharomyces
      cerevisiae inhibits growth. We tested four regions of E1A that alter growth and
      transcription in mammalian cells for their effects in yeast when expressed as
      fusions to the Gal4p DNA binding domain. Expression of the N-terminal/conserved
      region (CR) 1 or CR3, but not of the CR2 or the C-terminal portion of E1A,
      inhibited yeast growth. Growth inhibition was relieved by deletion of the genes
      encoding the yGcn5p, Ngg1p, or Spt7p components of the SAGA transcriptional
      regulatory complex, but not the Ahc1p component of the related ADA complex,
      indicating that the N-terminal/CR1 and CR3 regions of E1A target the SAGA complex
      independently. Expression of the pCAF acetyltransferase, a mammalian homologue of
      yGcn5p, also suppressed growth inhibition by either portion of E1A. Furthermore,
      the N-terminal 29 residues and the CR3 portion of E1A interacted independently
      with yGcn5p and pCAF in vitro. Thus, two separate regions of E1A target the
      yGcn5p component of the SAGA transcriptional activation complex. A subregion of
      the N-terminal/CR1 fragment spanning residues 30-69 within CR1 also inhibited
      yeast growth in a SAGA-dependent fashion. However, this region did not interact
      with yGcn5p or pCAF, suggesting that it makes a third contact with another SAGA
      component. Our results provide a new model system to elucidate mechanisms by
      which E1A and the SAGA complex regulate transcription and growth.

PMID- 12070147
TI  - Regulation of the Gts1p level by the ubiquitination system to maintain metabolic
      oscillations in the continuous culture of yeast.
AB  - Yeast cells exhibit sustained ultradian oscillations of energy metabolism in
      coupling with cell cycle and stress resistance oscillations in continuous
      culture. We have reported that the rhythmic expression of Gts1p is important for
      the maintenance of ultradian rhythms. Structurally, Gts1p contains sequence
      motifs similar to N-degron and the ubiquitin association domain, raising the
      possibility that the Gts1p level is regulated by degradation via ubiquitination.
      When the lysine residue at the putative ubiquitination site of the N-degron was
      substituted with arginine, both the protein level and half-life of mutant Gts1p
      increased. During continuous culture, the protein level of the mutant Gts1p was
      elevated and did not fluctuate, leading to the disappearance of metabolic
      oscillation within a day. Furthermore, using three Gts1ps containing mutations in
      the ubiquitin association domain, we showed that the lower the binding activity
      of the mutant Gts1ps for polyubiquitin in vitro, the higher the protein level in
      vivo. Expression of the mutant Gts1ps in the continuous culture resulted in an
      increase in Gts1p and early loss of the oscillation. Therefore, Gts1p is degraded
      through conjugation with ubiquitin, and the UBA domain promoted the degradation
      of ubiquitinated Gts1p, causing a fluctuation in protein level, which is required
      for the maintenance of metabolic oscillations.

PMID- 12070148
TI  - Pancreatic islet beta-cells transiently metabolize pyruvate.
AB  - Pancreatic beta-cell metabolism was followed during glucose and pyruvate
      stimulation of pancreatic islets using quantitative two-photon NAD(P)H imaging.
      The observed redox changes, spatially separated between the cytoplasm and
      mitochondria, were compared with whole islet insulin secretion. As expected, both
      NAD(P)H and insulin secretion showed sustained increases in response to glucose
      stimulation. In contrast, pyruvate caused a much lower NAD(P)H response and did
      not generate insulin secretion. Low pyruvate concentrations decreased cytoplasmic
      NAD(P)H without affecting mitochondrial NAD(P)H, whereas higher concentrations
      increased cytoplasmic and mitochondrial levels. However, the pyruvate-stimulated
      mitochondrial increase was transient and equilibrated to near-base-line levels.
      Inhibitors of the mitochondrial pyruvate-transporter and malate-aspartate shuttle
      were utilized to resolve the glucose- and pyruvate-stimulated NAD(P)H response
      mechanisms. These data showed that glucose-stimulated mitochondrial NAD(P)H and
      insulin secretion are independent of pyruvate transport but dependent on NAD(P)H
      shuttling. In contrast, the pyruvate-stimulated cytoplasmic NAD(P)H response was
      enhanced by both inhibitors. Surprisingly the malate-aspartate shuttle inhibitor
      enabled pyruvate-stimulated insulin secretion. These data support a model in
      which glycolysis plays a dominant role in glucose-stimulated insulin secretion.
      Based on these data, we propose a mechanism for glucose-stimulated insulin
      secretion that includes allosteric inhibition of tricarboxylic acid cycle enzymes
      and pH dependence of mitochondrial pyruvate transport.

PMID- 12070149
TI  - Peritoneal CD5+ B-1 cells have signaling properties similar to tolerant B cells.
AB  - CD5(+) B (or B-1) cells are the normal precursors of B cell chronic lymphocytic
      leukemia. They differ from conventional B (B-2) cells with respect to their
      phenotype and mitogenic responses and are often secretors of the natural
      polyreactive antibodies in the serum. The origin of B-1 cells remains
      controversial, and the relationship between B-1 cells and autoreactive B cells is
      unclear. Here, we compare the signaling pathways that are activated by the
      engagement of the B cell antigen receptor (BCR) in B-1 and B-2 cells. Stimulation
      of the BCR leads to the induced activation of the three major classes of mitogen
      activated protein kinases (MAPKs), ERK, JNK, and p38 MAPK, as well as the Akt
      kinase and the transcription factors nuclear factor of activated T cells (NF-AT)
      and NF-kappaB in B-2 cells. In contrast, B-1 cells have constitutive activation
      of ERK and NF-AT but exhibit delayed JNK and lack p38 MAPK and NF-kappaB
      induction upon BCR cross-linking. The lack of NF-kappaB activation in B-1 cells
      may be due to a lack of Akt activation in these cells. Furthermore, our study
      using specific inhibitors reveals that the extended survival of B-1 cells in
      culture is not due to the constitutive activation of ERK; nor is it due to Akt
      signaling or Bcl-x(L) up-regulation, since these are not induced in B-1 cells.
      The current findings of altered MAPK and NF-AT activation and lack of NF-kappaB
      induction in B-1 cells indicate that these cells have signaling properties
      similar to tolerant B cells that are chronically exposed to self-antigens.
      Indeed, BCR stimulation of B-1 cells does not lead to their full activation as
      indicated by their lack of maximal up-regulation of specific markers such as
      CD25, CD69, and CD86.

PMID- 12070150
TI  - The proto-oncogene c-myc acts through the cyclin-dependent kinase (Cdk) inhibitor
      p27(Kip1) to facilitate the activation of Cdk4/6 and early G(1) phase
      progression.
AB  - Progression through the early G(1) phase of the cell cycle requires mitogenic
      stimulation, which ultimately leads to the activation of cyclin-dependent kinases
      4 and 6 (Cdk4/6). Cdk4/6 activity is promoted by D-type cyclins and opposed by
      Cdk inhibitor proteins. Loss of c-myc proto-oncogene function results in a defect
      in the activation of Cdk4/6. c-myc(-/-) cells express elevated levels of the Cdk
      inhibitor p27(Kip1) and reduced levels of Cdk7, the catalytic subunit of Cdk
      activating kinase. We show here that in normal (c-myc(+/+)) cells, the majority
      of cyclin D-Cdk4/6 complexes are assembled with p27 and remain inactive during
      cell cycle progression; their function is presumably to sequester p27 from Cdk2
      complexes. A small fraction of Cdk4/6 protein was found in lower molecular mass
      catalytically active complexes. Conditional overexpression of p27 in c-myc(+/+)
      cells caused inhibition of Cdk4/6 activity and elicited defects in G(0)-to-S
      phase progression very similar to those seen in c-myc(-/-) cells. Overexpression
      of cyclin D1 in c-myc(-/-) cells rescued the defect in Cdk4/6 activity,
      indicating that the limiting factor is the number of cyclin D-Cdk4/6 complexes.
      Cdk-activating kinase did not rescue Cdk4/6 activity. We propose that the defect
      in Cdk4/6 activity in c-myc(-/-) cells is caused by the elevated levels of p27,
      which convert the low abundance activable cyclin D-Cdk4/6 complexes into
      unactivable complexes containing higher stoichiometries of p27. These
      observations establish p27 as a physiologically relevant regulator of cyclin D
      Cdk4/6 activity as well as mechanistically a target of c-Myc action and provide a
      model by which c-Myc influences the early-to-mid G(1) phase transition.

PMID- 12070152
TI  - Dominant negative effectors of heparin affin regulatory peptide (HARP) angiogenic
      and transforming activities.
AB  - Heparin affin regulatory peptide (HARP) is an heparin-binding growth factor,
      highly expressed in several primary human tumors and considered as a rate
      limiting angiogenic factor in tumor growth, invasion, and metastasis. Implication
      of this protein in carcinogenesis is linked to its mitogenic, angiogenic, and
      transforming activities. Recently, we have demonstrated that the C-terminal
      residues 111-136 of HARP are required for its mitogenic and transforming
      activities (Bernard-Pierrot, I., Delbe, J., Caruelle, D., Barritault, D., Courty,
      J., and Milhiet, P. E. (2001) J. Biol. Chem. 276, 12228-12234). In this paper,
      HARP deleted of its last 26 amino acids was shown to act as a dominant negative
      effector for its mitogenic, angiogenic, transforming, and tumor-formation
      activities by heterodimerizing with the wild type protein. Similarly, the
      synthetic corresponding peptide P111-136 displayed in vitro inhibition of wild
      type HARP activities, but in this case, the inhibition was mainly explained by
      the competition of the peptide with HARP for the binding to the extracellular
      domain of the high affinity ALK receptor.

PMID- 12070151
TI  - The activation of Rac1 by M3 muscarinic acetylcholine receptors involves the
      translocation of Rac1 and IQGAP1 to cell junctions and changes in the composition
      of protein complexes containing Rac1, IQGAP1, and actin.
AB  - The abilities of the M(3) muscarinic acetylcholine receptor (mAChR) and Rac1 to
      regulate similar cellular responses, including cadherin-mediated adhesion,
      prompted us to investigate Rac1 regulation by M(3) mAChR. We characterized
      changes in Rac1 induced by stimulating transfected M(3) mAChR in Chinese hamster
      ovary cells stably expressing hemagglutinin (HA)-tagged wild-type or mutant Rac1.
      mAChR activation converts endogenous Rac1 to the GTP-bound form in cells
      expressing HA-Rac1 but not in cells expressing dominant negative HA-Rac1(Asn-17)
      or constitutively active HA-Rac1(Val-12). The competitive binding of endogenous
      IQGAP1 by HA-Rac1(Val-12) may diminish the mAChR-mediated activation of
      endogenous Rac1. HA-Rac1 and HA-Rac1(Val-12), but not HA-Rac1(Asn-17), accumulate
      with IQGAP1 at cell junctions during mAChR-induced cell-cell compaction. Co
      localization studies suggest that Rac1 can accumulate at junctions without
      IQGAP1, but IQGAP1 cannot accumulate at junctions without Rac1. mAChR activation
      also induces GTP-independent changes in Rac1 because mAChR activation
      redistributes HA-Rac1(Asn-17), which does not bind GTP. Actin associates with
      complexes containing HA-Rac1 or HA-Rac1(Val-12) after prolonged mAChR activation.
      We also demonstrate that Rac1 participates in mAChR-induced cell-cell compaction
      and c-Jun phosphorylation. These results indicate that M(3) mAChR activation
      converts Rac1 to the GTP-bound form, alters interactions between Rac1, IQGAP1,
      and actin, and causes the junctional accumulation of Rac1 and IQGAP1.

PMID- 12070153
TI  - Identification of both positive and negative domains within the epidermal growth
      factor receptor COOH-terminal region for signal transducer and activator of
      transcription (STAT) activation.
AB  - The cytoplasmic region of human epidermal growth factor receptor (EGFR) contains
      an intrinsic tyrosine kinase (697-955) followed by a 231-residue-long COOH
      terminal tail (C-tail), which contains multiple tyrosine residues. To examine the
      role of the EGFR C-tail in signal transducer and activator of transcription
      (STAT) activation, a series of EGFR C-tail truncations were constructed.
      Transient transfection of 293 cells with EGFR lacking the C-tail, i.e.
      Y974DeltaEGFR or Y992DeltaEGFR, led to EGF-independent or constitutive STAT
      activation, whereas EGF-dependent STAT activation was restored with truncations
      made COOH-terminal to the next tyrosine residue, i.e. EGFR-Y1045Delta.
      Transfection with the-truncated form EGFR-Y954Delta resulted in the loss of STAT
      activation, suggesting that the sequence between Tyr(974) and Tyr(954) is
      essential for STAT activation. Phosphopeptide competition analysis revealed
      multiple tyrosine residues within the C-tail that can act as the docking sites
      for both Stat1 and Stat3. A region that negatively regulated STAT activation was
      also identified, extending from Tyr(1114) to Glu(1172), consistent with the
      ability of this region to recruit a suppressor of cytokine signaling factors
      SOCS1 and SOCS3. When cotransfected with the full-length EGFR, but not
      Y992DeltaEGFR, SOCS1 or SOCS3 inhibited STAT activation by EGF in 293 cells. This
      suggests that both SOCS1 and SOCS3 can negatively regulate EGFR activation,
      presumably by inducing ubiquitination-dependent EGFR degradation upon ligand
      binding. These findings may therefore offer clues to how the EGF receptor C-tail
      regulates STAT activity.

PMID- 12070154
TI  - Cells respond to and bind countin, a component of a multisubunit cell number
      counting factor.
AB  - In Dictyostelium discoideum counting factor (CF), a secreted approximately 450
      kDa complex of polypeptides, inhibits group and fruiting body size. When the gene
      encoding countin (a component of CF) was disrupted, cells formed large groups. We
      find that recombinant countin causes developing cells to form small groups, with
      an EC(50) of approximately 3 ng/ml, and affects cAMP signal transduction in the
      same manner as semipurified CF. Recombinant countin increases cell motility,
      decreases cell-cell adhesion, and regulates gene expression in a manner similar
      to the effect of CF. However, countin does not decrease adhesion or group size to
      the extent that semipurified CF does. A 1-min exposure of developing cells to
      countin causes an increase in F-actin polymerization and myosin phosphorylation
      and a decrease in myosin polymerization, suggesting that countin activates a
      rapid signal transduction pathway. (125)I-Labeled countin has countin
      bioactivity, and binding experiments suggest that vegetative and developing cells
      have approximately 53 cell-surface sites that bind countin with a K(D) of
      approximately 1.5 ng/ml or 60 pm. We hypothesize that countin regulates cell
      development through the same pathway as CF and that other proteins within the
      complex may modify the activity of countin and/or have independent size
      regulating activities.

PMID- 12070155
TI  - Natural truncation of the chemokine MIP-1 beta /CCL4 affects receptor specificity
      but not anti-HIV-1 activity.
AB  - Activated lymphocytes synthesize and secrete substantial amounts of the beta
      chemokines macrophage inflammatory protein (MIP)-1 alpha/CCL3 and MIP-1
      beta/CCL4, both of which inhibit infection of cells with human immunodeficiency
      virus type 1 (HIV-1). The native form of MIP-1 beta secreted by activated human
      peripheral blood lymphocytes (MIP-1 beta(3-69)) lacks the two NH(2)-terminal
      amino acids of the full-length protein. This truncated form of MIP-1 beta has now
      been affinity-purified from the culture supernatant of such cells, and its
      structure has been confirmed by mass spectrometry. Functional studies of the
      purified protein revealed that MIP-1 beta(3-69) retains the abilities to induce
      down-modulation of surface expression of the chemokine receptor CCR5 and to
      inhibit the CCR5-mediated entry of HIV-1 in T cells. Characterization of the
      chemokine receptor specificity of MIP-1 beta(3-69) showed that the truncated
      protein not only shares the ability of intact MIP-1 beta to induce Ca(2+)
      signaling through CCR5, but unlike the full-length protein, it also triggers a
      Ca(2+) response via CCR1 and CCR2b. These results demonstrate that NH(2)
      terminally truncated MIP-1 beta functions as a chemokine agonist with expanded
      receptor reactivity, which may represent an important mechanism for regulation of
      immune cell recruitment during inflammatory and antiviral responses.

PMID- 12070156
TI  - The unique pentagonal structure of an archaeal Rubisco is essential for its high
      thermostability.
AB  - We have previously determined the crystal structure of a novel pentagonal
      ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) from the
      hyperthermophilic archaeon, Thermococcus kodakaraensis KOD1. Here we have carried
      out biochemical studies to identify the necessities and/or advantages of this
      intriguing pentagonal structure. The structure indicated the presence of three
      neighboring residues (Glu-63, Arg-66, and Asp-69), participating in ionic
      interactions within unique dimer-dimer interfaces. We constructed three single
      mutant proteins (E63S, R66S, and D69S) and one triple mutant protein
      (E63S/R66S/D69S) by replacing the charged residues with serine. The wild type
      (WT) and all mutant proteins were purified and subjected to gel permeation
      chromatography at various temperatures. WT and D69S proteins were decameric at
      all temperatures examined between 30 and 90 degrees C. The majority of E63S and
      R66S were decamers at 30 degrees C but were found to gradually disassemble with
      the elevation in temperature. E63S/R66S/D69S was found in a dimeric form even at
      30 degrees C. An interesting correlation was found between the subunit assembly
      and thermostability of the proteins. Circular dichroism and differential scanning
      calorimetry analyses indicated that the denaturation temperatures of dimeric
      enzymes (E63S, R66S, and E63S/R66S/D69S) were approximately 95 degrees C, whereas
      those of the enzymes retaining a decameric structure (WT and D69S) were
      approximately 110 degrees C. Disassembly into tetramer or dimer units did not
      alter the slopes of the Arrhenius plots, indicating that the decameric structure
      had no effect on catalytic performance per se. The results indicate that the
      decameric assembly of Tk-Rubisco contributes to enhance the thermostability of
      the enzyme. Taking into account the growth temperature of strain KOD1 (65-100
      degrees C), the decameric structure of Tk-Rubisco can be considered essential for
      the stable presence of the enzyme in the host cells. This study provides an
      interesting example in which the thermostability of a protein can be enhanced by
      formation of a unique quaternary structure not found in mesophilic enzymes.

PMID- 12070157
TI  - Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes
      mediated by human cholesteryl ester transfer protein (CETP) in CETP
      transgenic/ApoCI-knocked out mice.
AB  - Transgenic mice expressing human cholesteryl ester transfer protein (HuCETPTg
      mice) were crossed with apolipoprotein CI-knocked out (apoCI-KO) mice. Although
      total cholesterol levels tended to be reduced as the result of CETP expression in
      HuCETPTg heterozygotes compared with C57BL6 control mice (-13%, not significant),
      a more pronounced decrease (-28%, p < 0.05) was observed when human CETP was
      expressed in an apoCI-deficient background (HuCETPTg/apoCI-KO mice). Gel
      permeation chromatography analysis revealed a significant, 6.1-fold rise (p <
      0.05) in the cholesteryl ester content of very low density lipoproteins in
      HuCETPTg/apoCI-KO mice compared with control mice, whereas the 2.7-fold increase
      in HuCETPTg mice did not reach the significance level in these experiments.
      Approximately 50% decreases in the cholesteryl ester content and cholesteryl
      ester to triglyceride ratio of high density lipoproteins (HDL) were observed in
      HuCETPTg/apoCI-KO mice compared with controls (p < 0.05 in both cases), with
      intermediate -20% changes in HuCETPTg mice. The cholesteryl ester depletion of
      HDL was accompanied with a significant reduction in their mean apparent diameter
      (8.68 +/- 0.04 nm in HuCETPTg/apoCI-KO mice versus 8.83 +/- 0.02 nm in control
      mice; p < 0.05), again with intermediate values in HuCETPTg mice (8.77 +/- 0.04
      nm). In vitro purified apoCI was able to inhibit cholesteryl ester exchange when
      added to either total plasma or reconstituted HDL-free mixtures, and
      coincidently, the specific activity of CETP was significantly increased in the
      apoCI-deficient state (173 +/- 75 pmol/microg/h in HuCETPTg/apoCI-KO mice versus
      72 +/- 19 pmol/microg/h in HuCETPTg, p < 0.05). Finally, HDL from apoCI-KO mice
      were shown to interact more readily with purified CETP than control HDL that
      differ only by their apoCI content. Overall, the present observations provide
      direct support for a potent specific inhibition of CETP by plasma apoCI in vivo.

PMID- 12070159
TI  - A model for constitutive lutropin receptor activation based on molecular
      simulation and engineered mutations in transmembrane helices 6 and 7.
AB  - Many naturally occurring and engineered mutations lead to constitutive activation
      of the G protein-coupled lutropin receptor (LHR), some of which also result in
      reduced ligand responsiveness. To elucidate the nature of interhelical
      interactions in this heptahelical receptor and changes thereof accompanying
      activation, we have utilized site-directed mutagenesis on transmembrane helices 6
      and 7 of rat LHR to prepare and characterize a number of single, double, and
      triple mutants. The potent constitutively activating mutants, D556(6.44)H and
      D556(6.44)Q, were combined with weaker activating mutants, N593(7.45)R and
      N597(7.49)Q, and the loss-of-responsiveness mutant, N593(7.45)A. The engineered
      mutants have also been simulated using a new receptor model based on the crystal
      structure of rhodopsin. The results suggest that constitutive LHR activation by
      mutations at Asp-556(6.44) is triggered by the breakage or weakening of the
      interaction found in the wild type receptor between Asp-556(6.44) and Asn
      593(7.45). Whereas this perturbation is unique to the activating mutations at Asp
      556(6.44), common features to all of the most active LHR mutants are the breakage
      of the charge-reinforced H-bonding interaction between Arg-442(3.50) and Asp
      542(6.30) and the increase in solvent accessibility of the cytosolic extensions
      of helices 3 and 6, which probably participate in the receptor-G protein
      interface. Asn-593(7.45) and Asn-597(7.49) also seem to be necessary for the high
      constitutive activities of D556(6.44)H and D556(6.44)Q and for full ligand
      responsiveness. The new theoretical model provides a foundation for further
      experimental work on the molecular mechanism(s) of receptor activation.

PMID- 12070158
TI  - Serine 577 is phosphorylated and negatively affects the tRNA binding and
      eIF2alpha kinase activities of GCN2.
AB  - Protein kinase GCN2 regulates translation initiation by phosphorylating
      eukaryotic initiation factor 2alpha (eIF2alpha), impeding general protein
      synthesis but specifically inducing translation of GCN4, a transcriptional
      activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. GCN2
      activity is stimulated in amino acid-deprived cells through binding of uncharged
      tRNA to a domain related to histidyl tRNA synthetase. We show that GCN2 is
      phosphorylated by another kinase on serine 577, located N-terminal to the kinase
      domain. Mutation of Ser-577 to alanine produced partial activation of GCN2 in
      nonstarved cells, increasing the level of phosphorylated eIF2alpha, derepressing
      GCN4 expression, and elevating the cellular levels of tryptophan and histidine.
      The Ala-577 mutation also increased the tRNA binding affinity of purified GCN2,
      which can account for the elevated kinase activity of GCN2-S577A in nonstarved
      cells where uncharged tRNA levels are low. Whereas Ser-577 remains phosphorylated
      in amino acid-starved cells, its dephosphorylation could mediate GCN2 activation
      in other stress or starvation conditions by lowering the threshold of uncharged
      tRNA required to activate the protein.

PMID- 12070160
TI  - Endocytic intermediates involved with the intracellular trafficking of a
      fluorescent cellular prion protein.
AB  - We have investigated the intracellular traffic of PrP(c), a
      glycosylphosphatidylinositol (GPI)-anchored protein implicated in spongiform
      encephalopathies. A fluorescent functional green fluorescent protein (GFP)-tagged
      version of PrP(c) is found at the cell surface and in intracellular compartments
      in SN56 cells. Confocal microscopy and organelle-specific markers suggest that
      the protein is found in both the Golgi and the recycling endosomal compartment.
      Perturbation of endocytosis with a dynamin I-K44A dominant-negative mutant
      altered the steady-state distribution of the GFP-PrP(c), leading to the
      accumulation of fluorescence in unfissioned endocytic intermediates. These pre
      endocytic intermediates did not seem to accumulate GFP-GPI, a minimum GPI
      anchored protein, suggesting that PrP(c) trafficking does not depend solely on
      the GPI anchor. We found that internalized GFP-PrP(c) accumulates in Rab5
      positive endosomes and that a Rab5 mutant alters the steady-state distribution of
      GFP-PrP(c) but not that of GFP-GPI between the plasma membrane and early
      endosomes. Therefore, we conclude that PrP(c) internalizes via a dynamin
      dependent endocytic pathway and that the protein is targeted to the recycling
      endosomal compartment via Rab5-positive early endosomes. These observations
      indicate that traffic of GFP-PrP(c) is not determined predominantly by the GPI
      anchor and that, different from other GPI-anchored proteins, PrP(c) is delivered
      to classic endosomes after internalization.

PMID- 12070161
TI  - Beta-amyloid enhances glial glutamate uptake activity and attenuates synaptic
      efficacy.
AB  - Although amyloid beta-protein (A beta) has long been implicated in the
      pathogenesis of Alzheimer's disease, little is known about the mechanism by which
      A beta causes dementia. A beta leads to neuronal cell death in vivo and in vitro,
      but recent evidence suggests that the property of the amnesic characteristic of
      Alzheimer's disease can be explained by a malfunction of synapses rather than a
      loss of neurons. Here we show that prolonged treatment with A beta augments the
      glutamate clearance ability of cultured astrocytes and induces a dramatic
      decrease in glutamatergic synaptic activity of neurons cocultured with the
      astrocytes. Biotinylation assay revealed that the enhancement of glutamate uptake
      activity was associated with an increase in cell-surface expression of GLAST, a
      subtype of glial glutamate transporters, without apparent changes in the total
      amount of GLAST. This phenomenon was blocked efficiently by actin-disrupting
      agents. Thus, A beta-induced actin-dependent GLAST redistribution and relevant
      synaptic malfunction may be a cellular basis for the amnesia of Alzheimer's
      disease.

PMID- 12070162
TI  - Neurosecretion competence. A comprehensive gene expression program identified in
      PC12 cells.
AB  - The phenotype of neurosecretory cells is characterized by clear vesicles and
      dense granules, both discharged by regulated exocytosis. However, these
      organelles are lacking completely in a few neurosecretion-incompetent clones of
      the pheochromocytoma PC12 line, in which other specific features are maintained
      (incompetent clones). In view of the heterogeneity of PC12 cells, a differential
      characterization of the incompetent phenotype based on the comparison of a single
      incompetent and a single wild-type clone would have been inconclusive. Therefore,
      we have compared two pairs of PC12 clones, studying in parallel the transcript
      levels of 4,200 genes and 19,000 express sequence tags (ESTs) by high density
      oligonucleotide arrays. After accurate data processing for quality control and
      filtration, a total of 755 transcripts, corresponding to 448 genes and 307 ESTs,
      was found consistently changed, with 46% up-regulated and 54% down-regulated in
      incompetent versus wild-type clones. Many but not all neurosecretion genes were
      profoundly down-regulated in incompetent cells. Expression of endocytosis genes
      was normal, whereas that of many nuclear and transcription factors, including
      some previously shown to play key roles in neurogenesis, was profoundly changed.
      Additional differences appeared in genes involved in signaling and metabolism.
      Taken together these results demonstrate for the first time that expression of
      neurosecretory vesicles and granules is part of a complex gene expression program
      that includes many other features that so far have not been recognized.

PMID- 12070163
TI  - Regulation of T cell receptor-induced activation of the Ras-ERK pathway by
      diacylglycerol kinase zeta.
AB  - T cell development in the thymus and activation of mature T cells in the
      periphery depend on signals stimulated by engagement of the T cell antigen
      receptor (TCR). Among the second messenger cascades initiated by TCR ligation
      include the phosphatidylinositol pathway where the membrane phospholipid,
      phosphatidylinositol 4,5-bisphosphate, is hydrolyzed to inositol 1,4,5
      trisphosphate and diacylglycerol (DAG). Inositol 1,4,5-trisphosphate signals a
      rise in intracellular free calcium, leading to translocation of nuclear factor of
      activated T cells into the nucleus. DAG activates RasGRP and protein kinase C
      theta. Because both RasGRP and protein kinase C theta are essential for thymocyte
      and T cell function, it is critical to understand how DAG is regulated. In this
      report, we demonstrate expression of DAG kinase zeta (DGKzeta, the enzyme that
      catalyzes the conversion of DAG to phosphatidic acid) in multiple lymphoid
      organs, with highest expression observed within the T cell compartment.
      Overexpression studies in Jurkat T cells indicate that DGKzeta interferes with
      TCR-induced Ras and ERK activation, AP-1 induction, and expression of the
      activation marker CD69. In contrast, TCR-stimulated calcium influx is not
      altered. Mutational analysis indicates that the kinase and DAG binding domains,
      but not the ankyrin repeats of DGKzeta, are required for its inhibitory effects.
      Collectively these studies demonstrate a potential role of DGKzeta to function as
      a selective negative regulator of DAG signaling on T cell activation and provide
      the first structure/function analysis of this enzyme in T cells.

PMID- 12070164
TI  - The coiled coil region (amino acids 129-250) of the tumor suppressor protein
      adenomatous polyposis coli (APC). Its structure and its interaction with
      chromosome maintenance region 1 (Crm-1).
AB  - The APC (adenomatous polyposis coli) tumor suppressor protein has many different
      intracellular functions including a nuclear export activity. Only little is known
      about the molecular architecture of the 2843-amino acid APC protein. Guided by
      secondary structure predictions we identified a fragment close to the N-terminal
      end, termed APC-(129-250), as a soluble and protease-resistant domain. We solved
      the crystal structure of APC-(129-250), which is monomeric and consists of three
      alpha-helices forming two separate antiparallel coiled coils. APC-(129-250)
      includes the nuclear export signal NES-(165-174) at the C-terminal end of the
      first helix. Surprisingly, the conserved hydrophobic amino acids of NES-(165-174)
      are buried in one of the coiled coils and are thus not accessible for interaction
      with other proteins. We demonstrate the direct interaction of APC-(129-250) with
      the nuclear export factor chromosome maintenance region 1 (Crm-1). This
      interaction is enhanced by the small GTPase Ran in its activated GTP-bound form
      and also by a double mutation in APC-(129-250), which deletes two amino acids
      forming two of the major interhelical interactions within the coiled coil. These
      observations hint to a regulatory mechanism of the APC nuclear export activity by
      NES masking.

PMID- 12070165
TI  - Identification of the proteoglycan binding site in apolipoprotein B48.
AB  - An initial event in atherosclerosis is the retention of lipoproteins within the
      intima of the vessel wall. Previously we identified Site B (residues 3359-3369)
      in apolipoprotein (apo) B100 as the proteoglycan binding sequence in low density
      lipoproteins (LDLs) and showed that the atherogenicity of apoB-containing
      lipoproteins is linked to their affinity for artery wall proteoglycans. However,
      both apoB100- and apoB48-containing lipoproteins are equally atherogenic even
      though Site B lies in the carboxyl-terminal half of apoB100 and is absent in
      apoB48. If binding to proteoglycans is a key step in atherogenesis, apoB48
      containing lipoproteins must bind to proteoglycans via other proteoglycan binding
      sites in the amino-terminal 48% of apoB. In vitro studies have identified five
      clusters of basic amino acids in delipidated apoB48 that bind negatively charged
      glycosaminoglycans. To determine which of these sites is functional on LDL
      particles, we analyzed the proteoglycan binding activity of recombinant human
      LDLs from transgenic mice or rat hepatoma cells. Substitution of neutral amino
      acids for the basic amino acids in Site B-Ib (residues 84-94) abolished the
      proteoglycan binding activity of recombinant apoB53. Carboxyl-truncated apoB80
      bound biglycan with higher affinity than apoB100 and apoB48. ApoB80 in which Site
      B was mutated had the same affinity for proteoglycans as apoB48. These data
      support the hypothesis that the carboxyl terminus of apoB100 "masks" Site B-Ib,
      the amino-terminal proteoglycan binding site, and that this site is exposed in
      carboxyl-truncated forms of apoB. The presence of a proteoglycan binding site in
      the amino-terminal region of apoB may explain why apoB48- and apoB100-containing
      lipoproteins are equally atherogenic.

PMID- 12070166
TI  - Molecular and spectroscopic analysis of the cytochrome cbb(3) oxidase from
      Pseudomonas stutzeri.
AB  - Cytochrome cbb(3) oxidase, a member of the heme-copper oxidase superfamily, is
      characterized by its high affinity for oxygen while retaining the ability to pump
      protons. These attributes are central to its proposed role in the microaerobic
      metabolism of proteobacteria. We have completed the first detailed spectroscopic
      characterization of a cytochrome cbb(3) oxidase, the enzyme purified from
      Pseudomonas stutzeri. A combination of UV-visible and magnetic CD spectroscopies
      clearly identified four low-spin hemes and the high-spin heme of the active site.
      This heme complement is in good agreement with our analysis of the primary
      sequence of the ccoNOPQ operon and biochemical analysis of the complex. Near-IR
      magnetic CD spectroscopy revealed the unexpected presence of a low-spin
      bishistidine-coordinated c-type heme in the complex. This was shown to be one of
      two c-type hemes in the CcoP subunit by separately expressing the subunit in
      Escherichia coli. Separate expression of CcoP also allowed us to unambiguously
      assign each of the signals associated with low-spin ferric hemes present in the X
      band EPR spectrum of the oxidized enzyme. This work both underpins future
      mechanistic studies on this distinctive class of bacterial oxidases and raises
      questions concerning the role of CcoP in electron delivery to the catalytic
      subunit.

PMID- 12070167
TI  - Solution NMR characterization of an unusual distal H-bond network in the active
      site of the cyanide-inhibited, human heme oxygenase complex of the symmetric
      substrate, 2,4-dimethyldeuterohemin.
AB  - The presence of variable static hemin orientational disorder about the alpha
      gamma-meso axis in the substrate complexes of mammalian heme oxygenase, together
      with the incomplete averaging of a second, dynamic disorder, for each hemin
      orientation, has led to NMR spectra with severe spectral overlap and loss of key
      two-dimensional correlations that seriously interfere with structural
      characterization in solution. We demonstrate that the symmetric substrate, 2,4
      dimethyldeuterohemin, yields a single solution species for which the dynamic
      disorder is sufficiently rapid to allow effective and informative (1)H NMR
      structural characterization. A much more extensive, effective, and definitive NMR
      characterization of the cyanide-inhibited, symmetric heme complex of human heme
      oxygenase shows that the active site structure, with some minor differences, is
      essentially the same as that for the native protohemin in solution and crystal. A
      unique distal network that involves particularly strong hydrogen bonds, as well
      as inter-aromatic contacts, is described that is proposed to stabilize the
      position of the catalytically critical distal helix Asp-140 carboxylate (Liu, Y.,
      Koenigs Lightning, L., Huang, H., Moenne-Loccoz, P., Schuller, D. J., Poulos, T.
      L., Loehr, T. M., and Ortiz de Montellano, P. R. (2000) J. Biol. Chem. 275, 34501
      34507). The potential role of this network in placing a water molecule to
      stabilize the hydroperoxy species and as a template for the condensation of the
      distal helix upon substrate binding are discussed.

PMID- 12070168
TI  - Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5
      hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel
      sequence motif.
AB  - A family of four closely related PDZ domain-containing membrane-associated
      guanylate kinase homologues (MAGUKs) is involved in the regulation of the amount
      and functional state of ionotropic glutamate receptors in excitatory synapses. To
      understand the mechanisms that determine the specificity of these interactions,
      we examined the structural basis of the highly selective association between the
      ionotropic GluR subunit GluR-A and synapse-associated protein 97 (SAP97). The C
      terminus of GluR-A bound to the PDZ domains of SAP97, but not to those of three
      related MAGUKs, PSD-93, PSD-95, and SAP102. Experiments with single PDZ domains
      indicated that the strongest contribution was by the second PDZ domain.
      Unexpectedly, mutation analysis of the GluR-A C terminus revealed that a
      tripeptide sequence SSG at position -9 to -11 plays an essential role in this
      binding, in addition to a C-terminal type I PDZ binding motif (leucine at C
      terminus and threonine at the -2 position). Analysis of the in vitro MAGUK
      binding properties of a GluR-D mutant with a one-residue deletion at the C
      terminus provides further support for the view that an SSG sequence located N
      terminally from a type I PDZ binding motif can mediate selective binding to SAP97
      and suggest the existence of a novel variation of the PDZ domain-peptide
      interaction.

PMID- 12070169
TI  - Differential roles of arrestin-2 interaction with clathrin and adaptor protein 2
      in G protein-coupled receptor trafficking.
AB  - The non-visual arrestins, arrestin-2 and arrestin-3, play a critical role in
      regulating the signaling and trafficking of many G protein-coupled receptors
      (GPCRs). Molecular insight into the role of arrestins in GPCR trafficking has
      suggested that arrestin interaction with clathrin, beta(2)-adaptin (the beta
      subunit of the adaptor protein AP2), and phosphoinositides contributes to this
      process. In the present study, we have attempted to better define the molecular
      basis and functional role of arrestin-2 interaction with clathrin and beta(2)
      adaptin. Site-directed mutagenesis revealed that the C-terminal region of
      arrestin-2 mediated beta(2)-adaptin and clathrin interaction with Phe-391 and Arg
      395 having an essential role in beta(2)-adaptin binding and LIELD (residues 376
      380) having an essential role in clathrin binding. Interestingly, arrestin-2
      R169E, an activated form of arrestin that binds to GPCRs in a phosphorylation
      independent manner, has significantly enhanced binding to beta(2)-adaptin and
      clathrin. This suggests that receptor-induced conformational changes in the C
      terminal tail of arrestin-2 will likely play a major role in mediating arrestin
      interaction with clathrin-coated pits. In an effort to clarify the role of these
      interactions in GPCR trafficking we generated arrestin mutants that were
      completely and selectively defective in either clathrin (arrestin-2-DeltaLIELD)
      or beta(2)-adaptin (arrestin-2-F391A) interaction. Analysis of these mutants in
      COS-1 cells revealed that arrestin/clathrin interaction was essential for agonist
      promoted internalization of the beta(2)-adrenergic receptor, while
      arrestin/beta(2)-adaptin interaction appeared less critical. Arrestin-2 mutants
      defective in both clathrin and beta(2)-adaptin binding functioned as effective
      dominant negatives in HEK293 cells and significantly attenuated beta(2)
      adrenergic receptor internalization. These mutants should prove useful in better
      defining the role of arrestins in mediating receptor trafficking.

PMID- 12070170
TI  - A single cell density-sensing factor stimulates distinct signal transduction
      pathways through two different receptors.
AB  - In Dictyostelium discoideum, cell density is monitored by levels of a secreted
      protein, conditioned medium factor (CMF). CMFR1 is a putative CMF receptor
      necessary for CMF-induced G protein-independent accumulation of the SP70 prespore
      protein but not for CMF-induced G protein-dependent inositol 1,4,5-trisphosphate
      production. Using recombinant fragments of CMF, we find that stimulation of the
      inositol 1,4,5-trisphosphate pathway requires amino acids 170-180, whereas SP70
      accumulation does not, corroborating a two-receptor model. Cells lacking CMFR1 do
      not aggregate, due to the lack of expression of several important early
      developmentally regulated genes, including gp80. Although many aspects of early
      developmental cAMP-stimulated signal transduction are mediated by CMF, CMFR1 is
      not essential for cAMP-stimulated cAMP and cGMP production or Ca(2+) uptake,
      suggesting the involvement of a second CMF receptor. Exogenous application of
      antibodies against either the region between a first and second or a second and
      third possible transmembrane domain of CMFR1 induces SP70 accumulation. Antibody-
      and CMF-induced gene expression can be inhibited by recombinant CMFR1
      corresponding to the region between the first and third potential transmembrane
      domains, indicating that this region is extracellular and probably contains the
      CMF binding site. These observations support a model where a one- or two
      transmembrane CMFR1 regulates gene expression and a G protein-coupled CMF
      receptor mediates cAR1 signal transduction.

PMID- 12070171
TI  - The APG8/12-activating enzyme APG7 is required for proper nutrient recycling and
      senescence in Arabidopsis thaliana.
AB  - The vacuole/lysosome serves an important recycling function during starvation and
      senescence in eukaryotes via a process called autophagy. Here bulk cytosolic
      constituents and organelles become sequestered in specialized autophagic
      vesicles, which then deliver their cargo to the vacuole for degradation. In
      yeasts, genetic screens have identified two novel post-translational modification
      pathways remarkably similar to ubiquitination that are required for autophagy.
      From searches of the Arabidopsis genome, we have identified gene families
      encoding proteins related to both the APG8 and -12 polypeptide tags and orthologs
      for all components required for their attachment. A single APG7 gene encodes the
      ATP-dependent activating enzyme that initiates both conjugation pathways.
      Phenotypic analysis of an APG7 disruption indicates that it is not essential for
      normal growth and development in Arabidopsis. However, the apg7-1 mutant is
      hypersensitive to nutrient limiting conditions and displays premature leaf
      senescence. mRNAs for both APG7 and APG8 preferentially accumulate as leaves
      senesce, suggesting that both conjugation pathways are up-regulated during the
      senescence syndrome. These findings show that the APG8/12 conjugation pathways
      have been conserved in plants and may have important roles in autophagic
      recycling, especially during situations that require substantial nitrogen and
      carbon mobilization.

PMID- 12070172
TI  - Insulin inhibits hepatocellular glucose production by utilizing liver-enriched
      transcriptional inhibitory protein to disrupt the association of CREB-binding
      protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene
      promoter.
AB  - Hormones regulate glucose homeostasis, in part, by controlling the expression of
      gluconeogenic enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK). Insulin
      and glucocorticoids reciprocally regulate PEPCK expression primarily at the level
      of gene transcription. We demonstrate here that glucocorticoids promote, whereas
      insulin disrupts, the association of CREB-binding protein (CBP) and RNA
      polymerase II with the hepatic PEPCK gene promoter in vivo. We also show that
      accessory factors, such as CCAAT/enhancer-binding protein beta (C/EBP beta), can
      recruit CBP to drive transcription. Insulin increases protein levels of liver
      enriched transcriptional inhibitory protein (LIP), an inhibitory form of C/EBP
      beta, in a phosphatidylinositol 3-kinase-dependent manner. LIP concomitantly
      replaces liver-enriched transcriptional activator protein on the PEPCK gene
      promoter, which can abrogate the recruitment of CBP and polymerase II,
      culminating in the repression of PEPCK expression and the attenuation of
      hepatocellular glucose production.

PMID- 12070174
TI  - Alteration of the C-terminal amino acid of tubulin specifically inhibits myogenic
      differentiation.
AB  - Detyrosination is an evolutionarily conserved post-translational modification of
      microtubule polymers that is known to be enhanced during early morphological
      differentiation of cultured myogenic cells (Gundersen, G. G., Khawaja, S., and
      Bulinski, J. C. (1989) J. Cell Biol. 109, 2275-2288). We proposed that altering
      the C terminus of alpha-tubulin by detyrosination plays a role in morphological
      differentiation. To test our hypothesis, we treated L6 myoblasts with 3
      nitrotyrosine (Eiserich, J. P., Estevez, A. G., Bamberg, T. V., Ye, Y. Z.,
      Chumley, P. H., Beckman, J. S., and Freeman, B. A. (1999) Proc. Natl. Acad. Sci.
      U. S. A. 96, 6365-6375), a nontoxic inhibitor that resulted in high level
      inhibition of microtubule detyrosination and low level incorporation of
      nitrotyrosine into microtubules. Even though microtubule stabilization or
      modification by acetylation still occurred normally, morphological
      differentiation was blocked; myoblasts neither elongated significantly nor fused.
      Nitrotyrosine treatment prevented synthesis or activation of markers of myogenic
      differentiation, including muscle-specific myosin, alpha-actin, integrin
      alpha(7), and myogenin. Consistent with this, myoblast integrin beta(1A) remained
      highly expressed. In contrast, the increase in beta-catenin level characteristic
      of early myogenesis was unaffected by treatment. These results show that the
      identity of the C-terminal residue of alpha-tubulin modulates microtubule
      activity, possibly because binding to or signaling from modified microtubules is
      required for the myogenic program.

PMID- 12070173
TI  - Ethanol-sensitive sites on the human dopamine transporter.
AB  - Previous studies have shown that ethanol enhanced [(3)H]dopamine uptake in
      Xenopus oocytes expressing the dopamine transporter (DAT). This increase in DAT
      activity was mirrored by an increase in the number of transporters expressed at
      the cell surface. In the present study, ethanol potentiated the function of DAT
      expressed in HeLa cells but inhibited the function of the related norepinephrine
      transporter (NET). Chimeras generated between DAT and NET were examined for
      ethanol sensitivity and demonstrated that a 76-amino acid region spanning
      transmembrane domains (TMD) 2 and 3 was essential for ethanol potentiation of DAT
      function. The second intracellular loop between TMD 2 and 3 of DAT, which differs
      from that of NET by four amino acids, was explored for possible sites of ethanol
      action. Site-directed mutagenesis was used to replace each of these residues in
      DAT with the corresponding residue in NET, and the resulting cRNA were expressed
      in Xenopus oocytes. We found that mutations G130T or I137F abolished ethanol
      potentiation of DAT function, whereas the mutations F123Y and L138F had no
      significant effect. These results identify novel sites in the second
      intracellular loop that are important for ethanol modulation of DAT activity.

PMID- 12070175
TI  - Functional knockout of the adenosine 5'-phosphosulfate reductase gene in
      Physcomitrella patens revives an old route of sulfate assimilation.
AB  - The reduction of adenosine 5'-phosphosulfate (APS) to sulfite catalyzed by
      adenosine 5'-phosphosulfate reductase is considered to be the key step of sulfate
      assimilation in higher plants. However, analogous to enteric bacteria, an
      alternative pathway of sulfate reduction via phosphoadenosine 5'-phosphosulfate
      (PAPS) was proposed. To date, the presence of the corresponding enzyme, PAPS
      reductase, could be neither confirmed nor excluded in plants. To find possible
      alternative routes of sulfate assimilation we disrupted the adenosine 5'
      phosphosulfate reductase single copy gene in Physcomitrella patens by homologous
      recombination. This resulted in complete loss of the correct transcript and
      enzymatic activity. Surprisingly, the knockout plants grew on sulfate as the sole
      sulfur source, and the concentration of thiols in the knockouts did not differ
      from the wild type plants. However, when exposed to a sublethal concentration of
      cadmium, the knockouts were more sensitive than wild type plants. When fed
      [(35)S]sulfate, the knockouts incorporated (35)S in thiols; the flux through
      sulfate reduction was approximately 50% lower than in the wild type plants. PAPS
      reductase activity could not be measured with thioredoxin as reductant, but a
      cDNA and a gene coding for this enzyme were detected in P. patens. The moss
      Physcomitrella patens is thus the first plant species wherein PAPS reductase was
      confirmed on the molecular level and also the first organism wherein both APS-
      and PAPS-dependent sulfate assimilation co-exist.

PMID- 12070176
TI  - Activation of retinoic acid receptor-dependent transcription by all-trans
      retinoic acid metabolites and isomers.
AB  - We have shown that four metabolites of all-trans-retinoic acid (ATRA) (4-oxo-, 4
      OH-, 18-OH-, and 5,6-epoxy-RA) can induce maturation of NB4 promyelocytic
      leukemia cells (Idres, N., Benoit, G., Flexor, M. A., Lanotte, M., and Chabot, G.
      G. (2001) Cancer Res. 61, 700-705). To better understand the mechanism of action
      of ATRA metabolites and isomers, we assessed their binding to retinoic acid
      receptors (RARs) and activation of RAR-mediated transcription via a retinoic acid
      response element (RARE). Competition binding experiments with tritiated ATRA
      showed that all metabolites could bind to RARs with variable affinity. For
      transactivation studies, COS-7 cells were cotransfected with RAR alpha, beta, or
      gamma expression vectors and the reporter plasmid RARE-tk-Luc, and the retinoid
      concentrations for half-maximal luciferase activity (EC(50)) were determined. All
      retinoids tested could activate the three RAR isotypes. The lowest EC(50) value
      for RAR alpha was with 9-cis-RA (13 nM), followed by 4-oxo-RA (33 nM), 5,6-epoxy
      RA (77 nM), 13-cis-RA (124 nM), 18-OH-RA (162 nM), ATRA (169 nM), and 4-OH-RA
      (791 nM). For RAR beta, the EC(50) values increased as follows: 4-oxo-RA (8 nM),
      ATRA (9 nM), 18-OH-RA (14 nM), 5,6-epoxy-RA (35 nM), 13-cis-RA (47 nM), 4-OH-RA
      (64 nM), and 9-cis-RA (173 nM). For RAR gamma the EC(50) values were: ATRA (2
      nM), 5,6-epoxy-RA (4 nM), 18-OH-RA (14 nM), 13-cis-RA (36 nM), 9-cis-RA (58 nM),
      4-oxo-RA (89 nM), and 4-OH-RA (94 nM). By comparing the -fold induction of
      luciferase activity, all retinoids tested were equipotent at transactivating RARE
      tk-Luc whatever the RAR considered. However, the best induction of the
      transcription was obtained for RAR alpha, which was 5-fold higher than for RAR
      beta and 10-fold higher than for RAR gamma. In conclusion, these data show that
      ATRA metabolites can bind to and activate the three RARs with variable relative
      affinity but with similar efficacy. These results suggest that ATRA metabolites
      may activate several signaling pathways and probably play an important role in
      cellular physiology and cancer therapy.

PMID- 12070177
TI  - Identification of a variant antioxidant response element in the promoter of the
      human glutamate-cysteine ligase modifier subunit gene. Revision of the ARE
      consensus sequence.
AB  - Constitutive and inducible expression of the gene encoding the modulator subunit
      of human glutamate-cysteine ligase (GCLM) is regulated by either of two regions
      of the promoter; an antioxidant response element (ARE) at -302:-291 and a 44-bp
      fragment (-346:-303) upstream of the ARE. This second region includes a consensus
      AP-1 site previously considered responsible for the enhancer activity of the
      upstream fragment. Deletion of a 165-bp fragment (-348:-183) including the ARE
      and upstream 44-bp fragment totally ablated t-butyl hydroquinone (tBHQ)
      inducibility of a GCLM promoter/luciferase transgene. Mutation analyses confirmed
      that both the ARE and the -346:-303 fragment could support induction following
      tBHQ exposure but demonstrated that induction in the latter case did not involve
      the AP-1 site at -341:-335. A region sharing significant homology with the
      consensus ARE sequence except for a single nucleotide mismatch at -330 (5'
      TTACnnnGCA-3' versus 5'-TGACnnnGCA-3') was identified at the 5'-end of the 44-bp
      fragment immediately adjacent to the AP-1 site. A G in this position has been
      considered an invariant requirement of functional ARE sequences. Mutation of T(
      330) to A (a substitution known to ablate ARE function) or C eliminated basal and
      inducible expression. Substitution of a G at -330 enhanced basal expression
      relative to the wild-type sequence, but induction following tBHQ exposure was
      comparable, indicating that either sequence (5'-TTACnnnGCA-3' versus 5'
      TGACnnnGCA-3') may function as an ARE, although the former sequence is less
      effective at directing basal expression. This possibility was confirmed by
      similar mutational analyses of the core sequence of hNQO1, a prototypic ARE.
      Electrophoretic mobility shift competition assays revealed that the 5'-TTACnnnGCA
      3' sequence could compete with the hNQO1 ARE for protein binding but was less
      effective than a similar probe containing the 5'-TGACnnnGCA-3' motif. Probes
      including the T(-330)A or T(-330)C mutations were ineffective. These results
      reveal that the GCLM promoter includes two functional AREs, one having a variant
      sequence. The results indicate that the consensus ARE sequence should be revised
      to 5'-RTKAYnnnGCR-3'.

PMID- 12070178
TI  - Cholesterol modulates the membrane binding and intracellular distribution of
      annexin 6.
AB  - Annexins are Ca(2+)- and phospholipid-binding proteins that are widely expressed
      in mammalian tissues and that bind to different cellular membranes. In recent
      years its role in membrane traffic has emerged as one of its predominant
      functions, but the regulation of its intracellular distribution still remains
      unclear. We demonstrated that annexin 6 translocates to the late endocytic
      compartment in low density lipoprotein-loaded CHO cells. This prompted us to
      investigate whether cholesterol, one of the major constituents of low density
      lipoprotein, could influence the membrane binding affinity and intracellular
      distribution of annexin 6. Treatment of crude membranes or early and late
      endosomal fractions with digitonin, a cholesterol-sequestering agent, displayed a
      strong reduction in the binding affinity of a novel EDTA-resistant and
      cholesterol-sensitive pool of annexin 6 proteins. In addition, U18666A-induced
      accumulation of cholesterol in the late endosomal compartment resulted in a
      significant increase of annexin 6 in these vesicles in vivo. This
      translocation/recruitment correlates with an increased membrane binding affinity
      of GST-annexin 6 to late endosomes of U18666A-treated cells in vitro. In
      conclusion, the present study shows that changes in the intracellular
      distribution and concentration of cholesterol in different subcellular
      compartments participate in the reorganization of intracellular pools of Ca(2+)
      dependent and -independent annexin 6.

PMID- 12070179
TI  - Biochemistry during the life and times of Hans Krebs and Fritz Lipmann.

PMID- 12070181
TI  - Waging war on physical inactivity: using modern molecular ammunition against an
      ancient enemy.
AB  - A hypothesis is presented based on a coalescence of anthropological estimations
      of Homo sapiens' phenotypes in the Late Paleolithic era 10,000 years ago, with
      Darwinian natural selection synergized with Neel's idea of the so-called thrifty
      gene. It is proposed that humans inherited genes that were evolved to support a
      physically active lifestyle. It is further postulated that physical inactivity in
      sedentary societies directly contributes to multiple chronic health disorders.
      Therefore, it is imperative to identify the underlying genetic and
      cellular/biochemical bases of why sedentary living produces chronic health
      conditions. This will allow society to improve its ability to effect beneficial
      lifestyle changes and hence improve the overall quality of living. To win the war
      against physical inactivity and the myriad of chronic health conditions produced
      because of physical inactivity, a multifactorial approach is needed, which
      includes successful preventive medicine, drug development, optimal target
      selection, and efficacious clinical therapy. All of these approaches require a
      thorough understanding of fundamental biology and how the dysregulated molecular
      circuitry caused by physical inactivity produces clinically overt disease. The
      purpose of this review is to summarize the vast armamentarium at our disposal in
      the form of the extensive scientific basis underlying how physical inactivity
      affects at least 20 of the most deadly chronic disorders. We hope that this
      information will provide readers with a starting point for developing additional
      strategies of their own in the ongoing war against inactivity-induced chronic
      health conditions.

PMID- 12070182
TI  - Cerebral cortical respiratory-related evoked potentials elicited by inspiratory
      occlusion in lambs.
AB  - Respiratory-related evoked potentials (RREP) elicited by inspiratory mechanical
      loads have been recorded in humans. Early RREP peaks were hypothesized to be
      generated by activation of neurons in the somatosensory cortex. An animal model
      was developed to test this hypothesis in chronically instrumented, awake,
      spontaneously breathing lambs. Electrocorticogram (ECoG) was recorded bilaterally
      with ball electrodes on the dural surface over the somatosensory region.
      Inspiratory occlusions were presented through a face mask or endotracheal tube as
      interruptions of inspiration. Occlusion-elicited evoked potentials were obtained
      by computer-signal averaging the ECoG activity. A short-latency positive peak was
      observed bilaterally in the averaged occlusion-elicited evoked potentials in all
      animals breathing with the facemask and 5 of 8 lambs with the endotracheal tube.
      Postmortem identification of the electrode location demonstrated that the ECoG
      was recorded in the caudal-lateral portion of the somatosensory cortex. These
      results demonstrate that inspiratory occlusion elicits an evoked potential in the
      somatosensory cortical region of awake, spontaneously breathing lambs. The lamb
      cortical RREP is similar to human RREP.

PMID- 12070183
TI  - Sequence variants in the FcepsilonRI alpha chain gene.
AB  - There is a relationship between IgE levels and expression of high-affinity IgE
      receptors (FcepsilonRI). Because the alpha chain is the only portion of the
      receptor that binds directly to IgE, we reasoned that sequence variants in the
      FcepsilonRI alpha gene may exist that alter these binding events. We screened all
      of the exons and the promoter region of the FcepsilonRI alpha chain gene with
      genomic DNA from 389 asthmatic and 341 normal control subjects for mutations by
      using single-stranded conformational polymorphism analysis. No nonsynonomous
      single nucleotide polymorphisms (SNPs) were identified in the coding region.
      Three SNPs were found in the promoter region: an A/C transversion at -770 from
      the translation start site; a G/A transition at -664; and a T/C transition at 
      335. No differences in allele frequencies were detected between asthmatic
      subjects and controls. Homozygosity for the C variant at locus -335 was more
      common in Caucasian asthmatic patients with IgE levels in the lower quartile than
      in the upper quartile (P = 0.032). An analysis of highly polymorphic SNPs
      indicated that this association is unlikely to be due to population substructure.
      We conclude that homozygosity for the C allele of FcepsilonRI alpha chain variant
      is associated with lower IgE levels.

PMID- 12070184
TI  - Luteal and follicular glucose fluxes during rest and exercise in 3-h
      postabsorptive women.
AB  - We examined the effects of exercise intensity and menstrual cycle phase on
      glucose flux rates during rest and exercise in rested and fed (3-h
      postabsorptive) women. Eight moderately active, eumenorrheic women were studied
      under conditions of rest (90 min) and exercise (60 min, leg ergometer cycling at
      45 and 65% peak oxygen consumption) during follicular and luteal phases. In both
      menstrual phases, an effect of exercise intensity was evident with glucose rates
      of appearance and disappearance and metabolic clearance rates: rest < 45%
      intensity < 65% intensity (P < 0.05). In addition, we observed no significant
      effect of menstrual phase on glucose rates of appearance and disappearance and
      metabolic clearance rate during rest or exercise at either intensity. These
      results are interpreted to mean that in women fed several hours before study 1)
      glucose flux is directly related to exercise intensity, 2) menstrual cycle phase
      does not alter glucose flux during rest and exercise, and 3) the subtle effects
      of endogenous ovarian hormones on glucose kinetics are subordinate to the much
      larger effects of exercise and recent carbohydrate nutrition.

PMID- 12070185
TI  - Detection of porcine oleic acid-induced acute lung injury using pulmonary
      acoustics.
AB  - To evaluate the utility of monitoring the sound-filtering characteristics of the
      respiratory system in the assessment of acute lung injury (ALI), we injected a
      multifrequency broadband sound signal into the airway of five anesthetized,
      intubated pigs, while recording transmitted sound over the trachea and on the
      chest wall. Oleic acid injections effected a severe lung injury predominantly in
      the dependent lung regions, increasing venous admixture from 6 +/- 1 to 54 +/- 8%
      (P < 0.05) and reducing dynamic respiratory system compliance from 19 +/- 0 to 12
      +/- 2 ml/cmH(2)O (P < 0.05). A two- to fivefold increase in sound transfer
      function amplitude was seen in the dependent (P < 0.05) and lateral (P < 0.05)
      lung regions; no change occurred in the nondependent areas. High within-subject
      correlations were found between the changes in dependent lung sound transmission
      and venous admixture (r = 0.82 +/- 0.07; range 0.74-0.90) and dynamic compliance
      (r = -0.87 +/- 0.05; -0.80 to -0.93). Our results indicate that the acoustic
      changes associated with oleic acid-induced lung injury allow monitoring of its
      severity and distribution.

PMID- 12070186
TI  - Effects of hyperthermia on cerebral blood flow and metabolism during prolonged
      exercise in humans.
AB  - The development of hyperthermia during prolonged exercise in humans is associated
      with various changes in the brain, but it is not known whether the cerebral
      metabolism or the global cerebral blood flow (gCBF) is affected. Eight endurance
      trained subjects completed two exercise bouts on a cycle ergometer. The gCBF and
      cerebral metabolic rates of oxygen, glucose, and lactate were determined with the
      Kety-Schmidt technique after 15 min of exercise when core temperature was similar
      across trials, and at the end of exercise, either when subjects remained
      normothermic (core temperature = 37.9 degrees C; control) or when severe
      hyperthermia had developed (core temperature = 39.5 degrees C; hyperthermia). The
      gCBF was similar after 15 min in the two trials, and it remained stable
      throughout control. In contrast, during hyperthermia gCBF decreased by 18% and
      was therefore lower in hyperthermia compared with control at the end of exercise
      (43 +/- 4 vs. 51 +/- 4 ml. 100 g(-1). min(-1); P < 0.05). Concomitant with the
      reduction in gCBF, there was a proportionally larger increase in the
      arteriovenous differences for oxygen and glucose, and the cerebral metabolic rate
      was therefore higher at the end of the hyperthermic trial compared with control.
      The hyperthermia-induced lowering of gCBF did not alter cerebral lactate release.
      The hyperthermia-induced reduction in exercise cerebral blood flow seems to
      relate to a concomitant 18% lowering of arterial carbon dioxide tension, whereas
      the higher cerebral metabolic rate of oxygen may be ascribed to a Q(10)
      (temperature) effect and/or the level of cerebral neuronal activity associated
      with increased exertion.

PMID- 12070187
TI  - Inhalation of warm and cold air does not influence brain stem or core temperature
      in normothermic humans.
AB  - The present study tested the hypothesis that inhalation rewarming provides a
      thermal increment to central neural structures adjacent to the nasopharyngeal
      region. Auditory-evoked brain stem responses of 14 subjects (7 men and 7 women)
      were monitored for 25 min while they inspired room air (24 degrees C) followed by
      hot air (41 degrees C) saturated with water vapor and cold dry air (-1 degrees
      C). The latencies of peaks I, III, and V and the interpeak latencies (IPLs) I
      III, III-V, and I-V were compared among the three conditions with a repeated
      measures ANOVA. Changes in IPLs are sensitive markers of changes in brain stem
      temperature. Tympanic temperature (T(ty)) was measured with an infrared tympanic
      thermometer. There were no significant differences in T(ty), peak latencies I,
      III, and V, and IPLs I-III, III-V, and I-V. The results indicate that inhalation
      of hot and cold air does not influence T(ty), nor does it influence the
      temperature of the brain stem. We conclude that inhalation rewarming is not
      capable of warming the vital central neural structures adjacent to the
      naropharynx.

PMID- 12070188
TI  - Age is independently related to muscle metabolic capacity in premenopausal women.
AB  - The purpose of this study was to determine whether muscle metabolic capacity was
      inversely related to age after adjusting for physical activity in sedentary
      premenopausal women. Eighty-three women (ages 23-47 yr) had their free-living,
      activity-related energy expenditure evaluated with doubly labeled water
      procedures, and room calorimeter determined sleeping energy expenditure. Maximum
      O(2) uptake and strength were evaluated in all subjects, whereas 31P-magnetic
      resonance spectroscopy determined metabolic economy during maximal exercise, and
      muscle biopsy maximal enzyme activity was evaluated in subsets of the sample (48
      and 18 subjects, respectively). Age was significantly related to whole body
      treadmill endurance time (r = -0.32), plantar flexion strength (r = -0.29),
      maximum O(2) uptake (r = -0.27), (31)P-magnetic resonance spectroscopy ADP
      recovery rate (r = -0.44), and anaerobic glycolytic capacity (r = -0.37), and
      muscle biopsy citrate synthase activity (r = -0.48), glyceraldehyde-3-phosphate
      dehydrogenase (r = -0.54), phosphofructokinase (r = -0.62), and phosphorylase (r
      = -0.58) activity even after adjusting for activity-related energy expenditure.
      These data suggest that, in sedentary premenopausal women, both oxidative and
      glycolytic muscle capacity decrease with age even when physical activity is taken
      into account.

PMID- 12070189
TI  - Effect of cold exposure on fuel utilization in humans: plasma glucose, muscle
      glycogen, and lipids.
AB  - The relative roles of circulatory glucose, muscle glycogen, and lipids in
      shivering thermogenesis are unclear. Using a combination of indirect calorimetry
      and stable isotope methodology ([U-13C]glucose ingestion), we have quantified the
      oxidation rates of these substrates in men acutely exposed to cold for 2 h
      (liquid conditioned suit perfused with 10 degrees C water). Cold exposure
      stimulated heat production by 2.6-fold and increased the oxidation of plasma
      glucose from 39.4 +/- 2.4 to 93.9 +/- 5.5 mg/min (+138%), of muscle glycogen from
      126.6 +/- 7.8 to 264.2 +/- 36.9 mg glucosyl units/min (+109%), and of lipids from
      46.9 +/- 3.2 to 176.5 +/- 17.3 mg/min (+376%). Despite the observed increase in
      plasma glucose oxidation, this fuel only supplied 10% of the energy for heat
      generation. The major source of carbohydrate was muscle glycogen (75% of all
      glucose oxidized), and lipids produced as much heat as all other fuels combined.
      During prolonged, low-intensity shivering, we conclude that total heat production
      is unequally shared among lipids (50%), muscle glycogen (30%), plasma glucose
      (10%), and proteins (10%). Therefore, future research should focus on lipids and
      muscle glycogen that provide most of the energy for heat production.

PMID- 12070190
TI  - Skin cooling maintains cerebral blood flow velocity and orthostatic tolerance
      during tilting in heated humans.
AB  - Orthostatic tolerance is reduced in the heat-stressed human. The purpose of this
      project was to identify whether skin-surface cooling improves orthostatic
      tolerance. Nine subjects were exposed to 10 min of 60 degrees head-up tilting in
      each of four conditions: normothermia (NT-tilt), heat stress (HT-tilt),
      normothermia plus skin-surface cooling 1 min before and throughout tilting (NT
      tilt(cool)), and heat stress plus skin-surface cooling 1 min before and
      throughout tilting (HT-tilt(cool)). Heating and cooling were accomplished by
      perfusing 46 and 15 degrees C water, respectively, though a tube-lined suit worn
      by each subject. During HT-tilt, four of nine subjects developed presyncopal
      symptoms resulting in the termination of the tilt test. In contrast, no subject
      experienced presyncopal symptoms during NT-tilt, NT-tilt(cool), or HT-tilt(cool).
      During the HT-tilt procedure, mean arterial blood pressure (MAP) and cerebral
      blood flow velocity (CBFV) decreased. However, during HT-tilt(cool), MAP, total
      peripheral resistance, and CBFV were significantly greater relative to HT-tilt
      (all P < 0.01). No differences were observed in calculated cerebral vascular
      resistance between the four conditions. These data suggest that skin-surface
      cooling prevents the fall in CBFV during upright tilting and improves orthostatic
      tolerance, presumably via maintenance of MAP. Hence, skin-surface cooling may be
      a potent countermeasure to protect against orthostatic intolerance observed in
      heat-stressed humans.

PMID- 12070191
TI  - Spinoreticular neurons that receive group III input are inhibited by MLR
      stimulation.
AB  - In decerebrate paralyzed cats, we examined the responses of 18 spinoreticular
      neurons to electrical stimulation of the mesencephalic locomotor region. The
      activity of each of the spinoreticular neurons was recorded extracellularly from
      laminae IV through VI of the L(7) and S(1) spinal cord. In addition, each of the
      18 spinoreticular neurons received group III afferent input from the tibial
      nerve. Spinoreticular projections were established for each of 18 neurons by
      antidromic invasion of the ventro lateral medulla at the P11 though P14 levels.
      The onset latencies and current thresholds for antidromic invasion from the
      ventro lateral medulla averaged 15.0 +/- 3.8 ms and 117 +/- 11 microA,
      respectively. Electrical stimulation of the mesencephalic locomotor region
      attenuated the spontaneous activity or the responses of each of the
      spinoreticular neurons to tibial nerve stimulation at currents that recruited
      group III afferents. Our data support the notion that thin-fiber muscle afferent
      input to the ventrolateral medulla is gated by a central command to exercise.

PMID- 12070193
TI  - beta-Adrenergic signaling and thyroid hormones affect HSP72 expression during
      heat acclimation.
AB  - Heat acclimation upregulates 72-kDa heat shock protein (HSP72) and predisposes to
      faster activation of the heat shock response (HSR). This study investigates the
      role played by beta-adrenergic signaling and/or plasma thyroxine level in
      eliciting these features by using rats undergoing 1) heat acclimation (AC; 34
      degrees C, 2 and 30 days); 2) AC with beta-adrenergic blockade; 3) AC-maintained
      euthyroid; 4) hypothyroid; 5) hyperthyroid; and 6) controls. The hsp72 mRNA (RT
      PCR) and HSP72 levels (Western blot) were measured before and after heat stress
      (2 h, 41 degrees C, rectal temperature monitored). beta-Adrenergic blockade
      during AC abolished HSP72 accumulation, without disrupting HSR. Low thyroxine
      blunted the HSR at posttranscriptional level, whereas thyroxine administration in
      hyperthyroid and AC-maintained euthyroid rats arrested heat stress-evoked hsp72
      transcription. We conclude that beta-adrenergic signaling contributes to the high
      HSP72 level characterizing the AC state. Thyroxine has two opposing effects: 1)
      direct repressive on rapid hsp72 transcription after heat stress; and 2) indirect
      stimulatory via beta-adrenergic signaling. Low thyroxine could account for
      diminished HSP72 synthesis via lower heat production and thermoregulatory set
      point.

PMID- 12070192
TI  - Anti-inflammatory agent, dexamethasone, does not affect exercise-induced arterial
      hypoxemia in Thoroughbreds.
AB  - In view of the suggestion that pulmonary injury-induced release of histamine
      and/or other chemical mediators from airway inflammatory and mast cells
      contribute to the exercise-induced arterial hypoxemia (EIAH) in human athletes,
      we examined the effects of pretreatment with a potent anti-inflammatory agent,
      dexamethasone, on EIAH and desaturation of hemoglobin in horses. Seven healthy,
      sound, exercise-trained Thoroughbreds were studied in the control (no
      medications) experiments, followed in 7 days by intravenous dexamethasone (0.11
      mg.kg(-1).day(-1) for 3 consecutive days) studies. Blood-gas measurements were
      made at rest and during incremental exercise leading to maximal exertion at 14
      m/s on a 3.5% uphill grade. Galloping at this workload induced pulmonary
      hemorrhage in all horses in both treatments, thereby indicating that stress
      failure of pulmonary capillaries had occurred. In both treatments, significant
      EIAH, desaturation of hemoglobin, hypercapnia, acidosis, and hyperthermia
      developed during maximal exercise, but significant differences between the
      control and dexamethasone treatments were not discerned. The failure of
      pretreatment with dexamethasone to significantly affect EIAH suggests that
      pulmonary injury-evoked airway inflammatory response may not play a major role in
      EIAH in racehorses. However, our observations in both treatments that EIAH
      developed quickly (being evident at 30 s of exertion) and that its severity
      remained unaffected by increasing exercise duration (to 120 s) suggest that EIAH
      has a functional basis, probably related to significant shortening of the transit
      time for blood in the pulmonary capillaries as cardiac output increases
      dramatically.

PMID- 12070195
TI  - Down training of the elderly soleus H reflex with the use of a spinally induced
      balance perturbation.
AB  - The purpose of this study was to determine the ability of the elderly central
      nervous system to modulate spinal reflex output to functionally decrease a
      spinally induced balance perturbation. In this case, the soleus H reflex was used
      as the source of perturbation. Therefore, decreasing (down training) of the
      soleus H reflex was necessary to counteract this perturbation and to better
      maintain postural control. In addition to assessing the effect of this
      perturbation on the H reflex, static postural stability was measured to evaluate
      possible functional effects. Ten healthy young subjects (age: 27.0 +/- 4.6 yr)
      and 10 healthy elderly subjects (age: 71.4 +/- 5.1 yr) participated in this
      study. Subjects underwent balance perturbation on 2 consecutive days. On day 1 of
      perturbation, significant down training of the soleus H reflex was demonstrated
      in both young (-20.4%) and elderly (-18.7%) subjects. On day 2 of perturbation,
      significant down training of the soleus H reflex was again demonstrated in both
      young (-24.6%) and elderly (-21.0%) subjects. Analysis of static stability after
      the 2 days of balance perturbation revealed a significant 10.1% decrease in the
      area of sway in elderly subjects. In conclusion, this study demonstrated that
      healthy, elderly subjects compared with young subjects were equally capable of
      down training the soleus H reflex in response to a balance perturbation.
      Furthermore, the improvement in static stability through balance training may
      provide further evidence that balance can be retrained and rehabilitated in
      subjects with decreased reflex function.

PMID- 12070194
TI  - Role of lung inflammatory mediators as a cause of exercise-induced arterial
      hypoxemia in young athletes.
AB  - We examined whether lung inflammatory mediators are increased during exercise and
      whether pharmacological blockade can prevent exercise-induced arterial hypoxemia
      (EIAH) in young athletes. Seventeen healthy athletes (9 men, 8 women; age 23 +/-
      3 yr) with varying degrees of EIAH completed maximal incremental treadmill
      exercise tests after administration of fexofenadine, zileuton, and nedocromil
      sodium or placebo in a randomized double-blind crossover study. Lung function,
      arterial blood gases, and inflammatory metabolites in plasma, urine, and induced
      sputum were assessed. Drug administration did not improve EIAH or gas exchange
      during exercise. At maximal exercise, oxygen saturation fell to 91.4 +/- 2.6%
      (drug trial) and 91.9 +/- 2.1% (placebo trial) and alveolar-arterial oxygen
      difference widened to 28.1 +/- 6.3 Torr (drug trial) and 29.3 +/- 5.7 Torr
      (placebo trial). Oxygen consumption, ventilation, and other exercise variables
      were similarly unaffected by drug treatment. Although plasma histamine increased
      with exercise, values did not differ between trials, and urinary leukotriene E(4)
      and 11beta-prostaglandin F(2alpha) levels were unchanged after exercise.
      Postexercise sputum revealed no significant changes in markers of inflammation.
      These results demonstrate that EIAH in young athletes is not attenuated with
      acute administration of drugs targeting histamine and bioactive lipids. We
      conclude that airway inflammation is of insufficient magnitude to cause
      impairments in gas exchange and does not appear to be linked to EIAH in healthy
      young athletes.

PMID- 12070196
TI  - Elevation in resting blood flow attenuates exercise hyperemia.
AB  - These experiments tested the hypothesis that elevating muscle blood flow before
      exercise would wash out vasoactive substances produced by muscle contraction and
      reduce the magnitude of exercise hyperemia and/or delay the response. In
      chronically instrumented dogs (n = 7), hindlimb blood flow was measured with
      chronically implanted flow probes during mild treadmill exercise. In an
      anesthetized preparation (n = 8), arterial and venous blood flows of a single
      hindlimb were obtained during 1-s tetanic contractions evoked by electrical
      stimulation of the cut sciatic nerve. Elevation of blood flow by intra-arterial
      infusion of adenosine attenuated the increase in flow during exercise and tetanic
      contraction by 48 and 47%, respectively. No delay was observed in the latency to
      peak flow. The attenuated hyperemic response to exercise or contraction is best
      explained by washout of vasoactive substance(s) produced by contracting muscle,
      but the residual response suggests that a metabolic mediator may not be the sole
      explanation for exercise hyperemia.

PMID- 12070197
TI  - Correlations using the NREM-REM sleep cycle frequency support distinct regulation
      mechanisms for REM and NREM sleep.
AB  - Polysomnograms of most homeothermic species distinguish two states, rapid eye
      movement (REM) and non-REM (NREM) sleep. These alternate several times during the
      night for reasons and following rules that remain poorly understood. It is
      unknown whether each state has its own function and regulation or whether they
      represent two facets of the same process. The present study compared the mean
      REM/NREM sleep ratio and the mean number of NREM-REM sleep cycles across 3
      consecutive nights. The rationale was that, if REM and NREM sleep are tightly
      associated, their ratio should be comparable whatever the cycle frequency in the
      night. Twenty-six healthy subjects of both sexes were recorded at their home for
      4 consecutive nights. The correlation between the REM/NREM sleep ratio and the
      number of cycles was highly significant. Of the two sleep components, REM sleep
      was associated to the number of cycles, whereas NREM sleep was not. This suggests
      that the relationship between REM sleep and NREM sleep is rather weak within
      cycles, does not support the concept of NREM-REM sleep cycles as miniature units
      of the sleep process, and favors the concept of distinct mechanisms of regulation
      for the two components.

PMID- 12070198
TI  - Lymphocyte apoptosis after exhaustive and moderate exercise.
AB  - Apoptosis or programmed cell death is a process of fundamental importance for
      regulation of the immune response. Several reasons suggest that apoptosis is
      involved in exercise-induced alterations of the immune system such as
      postexercise lymphocytopenia. Healthy volunteers performed two treadmill exercise
      tests; the first was performed at 80% maximal oxygen uptake until exhaustion
      (exhaustive exercise) and the second 2 wk later at 60% maximal oxygen uptake with
      the identical running time (moderate exercise). Blood samples were taken before,
      immediately after, and 1 h after the test. Lymphocytes were analyzed for
      apoptotic and necrotic cells by using FITC-labeled annexin V-antibodies and
      nuclear propidium iodide uptake, respectively. In addition, apoptotic/necrotic
      cells were measured after a 24-h incubation of lymphocytes in the presence of
      camptothecin or phytohemagglutinin. Finally, plasma membrane expression of CD95
      receptor and CD95-receptor ligand was investigated. Immediately after the
      exhaustive exercise, the percentage of apoptotic cells increased significantly,
      whereas it remained unchanged after the moderate exercise. Similar results were
      obtained after 24-h incubation of lymphocytes in medium alone or in the presence
      of camptothecin, but not with phytohemagglutinin. We found an upregulation of
      CD95-receptor expression after both exercise tests. However, only after
      exhaustive exercise a characteristic shift in CD95 expression profile toward
      cells with a high receptor density was observed. Expression of the CD95-receptor
      ligand remained unchanged after both exhaustive and moderate exercise. These
      results suggest that apoptosis may contribute to the regulation of the immune
      response after exhaustive exercise. Whether this mechanism can be regarded either
      as beneficial, i.e., deletion of autoreactive cells, or harmful, i.e.,
      suppression of the immune response, awaits further investigations.

PMID- 12070199
TI  - Influence of hyperpnea on airway surface fluid volume and osmolarity in normal
      humans.
AB  - To determine the effect of hyperpnea on the characteristics of periciliary
      liquid, we collected airway surface fluid (ASF) and measured its osmolarity in 11
      normal people while they breathed dry, frigid air (-17 +/- 1.2 degrees C) at
      minute ventilations (VE) of 10, 40, and 80 l/min through a heat exchanger. The
      ASF was collected at the fifth tracheal ring by absorption onto filter paper
      pledgets inserted via fiber-optic bronchoscopy. Hyperpnea had no influence on the
      amount of ASF recovered (ASF volume at a VE of 10 l/min = 12.0 +/- 2.0 microl; at
      80 l/min = 8.8 +/- 1.5 microl; P = 0.28) or its osmolarity (at a VE of 10, 40,
      and 80 l/min = 326 +/- 15, 323 +/- 11, and 337 +/- 12 mosM, respectively; P =
      0.65). These findings demonstrate that the tracheal mucosa of normal subjects
      does not dessicate during hyperpnea and that hypertonicity of the periciliary
      fluid does not develop even at high levels of ventilation.

PMID- 12070200
TI  - Dietary nucleotides prevent decrease in cellular immunity in ground-based
      microgravity analog.
AB  - Microgravity and stress of spaceflights result in immune dysfunction. The role of
      nutrition, especially nucleotide supplementation, has become an area of intensive
      research and significant interest in immunomodulation for maintenance of cellular
      immune responses. The studies presented here evaluate the plausibility of
      administering nucleotides to obviate immune dysfunction in an Earth-based in vivo
      analog of microgravity as studied in anti-orthostatic tail suspension (AOS) of
      mice. Mice were divided into three housing groups: group, isolation, and AOS.
      Mice were fed either control chow diet (CD), or RNA-, adenine-, or uracil
      supplemented CD for the 1-wk duration of the experiments. In AOS mice,
      supplemental nucleotides significantly increased in vivo lymph node proliferation
      and ex vivo lymphoproliferation response to alloantigen and mitogens,
      respectively, and interleukin-2 and interferon-gamma production. A lower
      corticosterone level was observed in uracil-supplemented CD compared with CD.
      These results suggest that exogenous nucleotide supplementation, especially
      uracil, of normal diet is beneficial in the maintenance and restoration of the
      immune response during the microgravity analog conditions.

PMID- 12070201
TI  - Effects of prior heavy exercise on VO(2) kinetics during heavy exercise are
      related to changes in muscle activity.
AB  - We hypothesized that the elevated primary O(2) uptake (VO(2)) amplitude during
      the second of two bouts of heavy cycle exercise would be accompanied by an
      increase in the integrated electromyogram (iEMG) measured from three leg muscles
      (gluteus maximus, vastus lateralis, and vastus medialis). Eight healthy men
      performed two 6-min bouts of heavy leg cycling (at 70% of the difference between
      the lactate threshold and peak VO(2)) separated by 12 min of recovery. The iEMG
      was measured throughout each exercise bout. The amplitude of the primary VO(2)
      response was increased after prior heavy leg exercise (from mean +/- SE 2.11 +/-
      0.12 to 2.44 +/- 0.10 l/min, P < 0.05) with no change in the time constant of the
      primary response (from 21.7 +/- 2.3 to 25.2 +/- 3.3 s), and the amplitude of the
      VO(2) slow component was reduced (from 0.79 +/- 0.08 to 0.40 +/- 0.08 l/min, P <
      0.05). The elevated primary VO(2) amplitude after leg cycling was accompanied by
      a 19% increase in the averaged iEMG of the three muscles in the first 2 min of
      exercise (491 +/- 108 vs. 604 +/- 151% increase above baseline values, P < 0.05),
      whereas mean power frequency was unchanged (80.1 +/- 0.9 vs. 80.6 +/- 1.0 Hz).
      The results of the present study indicate that the increased primary VO(2)
      amplitude observed during the second of two bouts of heavy exercise is related to
      a greater recruitment of motor units at the onset of exercise.

PMID- 12070202
TI  - Effect of aerobic and resistance exercise on central hemodynamic responses in
      severe chronic heart failure.
AB  - Exercise is now considered an important component of management in chronic heart
      failure (CHF), but little is known about central hemodynamic changes that occur
      during different exercise modalities in these patients. Seventeen patients
      (ejection fraction 25 +/- 2%) undertook brachial artery and right heart
      catheterization and oxygen consumption assessment at rest, during submaximal and
      peak cycling (Cyc), and during submaximal upper and lower limb resistance
      exercise. Cardiac output (CO) increased relative to baseline during peak Cyc (P <
      0.05) but did not change during submaximal Cyc or upper or lower limb exercise.
      Heart rate (HR) was lowest during upper limb exercise and progressively increased
      during lower limb exercise, submaximal Cyc, and peak Cyc, with significant
      differences between each of these (P < 0.01). Conversely, stroke volume (SV)
      decreased during submaximal Cyc and lower limb exercise and was lower during peak
      and submaximal Cyc and lower limb exercise than during upper limb exercise (P <
      0.05). CHF patients are dependent on increases in HR to increase CO during
      exercise when SV may decline. Resistance exercise, performed at appropriate
      intensity, induces a similar hemodynamic burden to aerobic exercise in patients
      with CHF.

PMID- 12070203
TI  - Alveolar hypercapnia augments pulmonary C-fiber responses to chemical stimulants:
      role of hydrogen ion.
AB  - To determine whether the excitabilities of pulmonary C fibers to chemical and
      mechanical stimuli are altered by CO(2)-induced acidosis, single-unit pulmonary C
      fiber activity was recorded in anesthetized, open-chest rats. Transient alveolar
      hypercapnia (HPC) was induced by administering CO(2)-enriched gas mixture (15%
      CO(2), balance air) via the respirator inlet for 30 s, which rapidly lowered the
      arterial blood pH from a baseline of 7.40 +/- 0.01 to 7.17 +/- 0.02. Alveolar HPC
      markedly increased the responses of these C-fiber afferents to several chemical
      stimulants. For example, the C-fiber response to right atrial injection of the
      same dose of capsaicin (0.25-1.0 microg/kg) was significantly increased from 3.07
      +/- 0.70 impulses/s at control to 8.48 +/- 1.52 impulses/s during HPC (n = 27; P
      < 0.05), and this enhanced response returned to control within approximately 10
      min after termination of HPC. Similarly, alveolar HPC also induced significant
      increases in the C-fiber responses to right atrial injections of phenylbiguanide
      (4-8 microg/kg) and adenosine (0.2 mg/kg). In contrast, HPC did not change the
      response of pulmonary C fibers to lung inflation. Furthermore, the peak response
      of these C fibers to capsaicin during HPC was greatly attenuated when the HPC
      induced acidosis was buffered by infusion of bicarbonate (1.36-1.82 mmol. kg(-1).
      min(-1) for 35 s). In conclusion, alveolar HPC augments the responses of these
      afferents to various chemical stimulants, and this potentiating effect of CO(2)
      is mediated through the action of hydrogen ions on the C-fiber sensory terminals.

PMID- 12070204
TI  - Ambient oxygen regulates epithelial metabolism and nitric oxide production in the
      human nose.
AB  - The effects of ambient O(2) tension on epithelial metabolism and nitric oxide
      (NO) production (VNO) in the nasal airway were examined in nine healthy
      volunteers. Nasal VNO, O(2) consumption (VO(2)), and CO(2) production (VCO(2))
      were measured during normoxia followed by gradual hypoxia from 21 to 0% O(2)
      concentration. Nasal VO(2), VCO(2), and respiratory quotient during normoxia were
      determined to be 1.19 +/- 0.04 ml/min, 1.60 +/- 0.04 ml/min, and 1.35 +/- 0.04,
      respectively. Hypoxia exposure to the nasal cavity significantly decreased both
      VCO(2) and VNO [VCO(2): 1.60 +/- 0.04 to 0.96 +/- 0.03 ml/min (P < 0.01), VNO:
      530 +/- 15 to 336 +/- 9 nl/min (P < 0.01)]. VNO was reduced commensurately with
      gradual decline in O(2) tension, and the apparent K(m) value for O(2) was
      determined to be 23.0 microM. These results indicate that the nasal epithelial
      cells exchange O(2) and CO(2) with ambient air in the course of their metabolism
      and that nasal epithelial cells can synthesize NO by using ambient O(2) as a
      substrate. We conclude that air-borne O(2) diffuses into the epithelium where it
      may be utilized for either cell metabolism or NO synthesis.

PMID- 12070205
TI  - Modeling the acute- and late-phase responses to peripheral airway cooling and
      desiccation.
AB  - Acute bronchoconstriction after isocapnic hyperpnea can be produced in most
      asthmatic individuals. However, the existence of a late-phase response is less
      certain. We used a canine model of isocapnic hyperpnea to test the hypothesis
      that this discrepancy is due to differences in the challenge threshold for the
      responses. Acute-phase and late-phase bronchoconstriction was measured in nine
      dogs after peripheral airway exposure to unconditioned air. Additionally,
      bronchoalveolar lavage fluid (BALF) was obtained during the late-phase response.
      The acute-phase response was a polynomial function with a decreasing slope at
      higher challenges, whereas the late-phase response suggested that a minimum
      threshold of challenge severity was needed to produce late-phase
      bronchoconstriction. BALF leukocyte and eicosanoid concentrations had linear
      relationships with challenge severity. Our data support the hypothesis that acute
      and late-phase posthyperpnea responses have different dose-response
      relationships, a fact that may explain the frequent lack of a late-phase
      response. However, our data suggest that mild inflammation can be induced with
      relatively lower challenge severity.

PMID- 12070206
TI  - Effects of respiratory muscle unloading on exercise-induced diaphragm fatigue.
AB  - We previously compared the effects of increased respiratory muscle work during
      whole body exercise and at rest on diaphragmatic fatigue and showed that the
      amount of diaphragmatic force output required to cause fatigue was reduced
      significantly during exercise (Babcock et al., J Appl Physiol 78: 1710, 1995). In
      this study, we use positive-pressure proportional assist ventilation (PAV) to
      unload the respiratory muscles during exercise to determine the effects of
      respiratory muscle work, per se, on exercise-induced diaphragmatic fatigue. After
      8-13 min of exercise to exhaustion under control conditions at 80-85% maximal
      oxygen consumption, bilateral phrenic nerve stimulation using single-twitch
      stimuli (1 Hz) and paired stimuli (10-100 Hz) showed that diaphragmatic pressure
      was reduced by 20-30% for up to 60 min after exercise. Usage of PAV during heavy
      exercise reduced the work of breathing by 40-50% and oxygen consumption by 10-15%
      below control. PAV prevented exercise-induced diaphragmatic fatigue as determined
      by bilateral phrenic nerve stimulation at all frequencies and times postexercise.
      Our study has confirmed that high- and low-frequency diaphragmatic fatigue result
      from heavy-intensity whole body exercise to exhaustion; furthermore, the data
      show that the workload endured by the respiratory muscles is a critical
      determinant of this exercise-induced diaphragmatic fatigue.

PMID- 12070207
TI  - Elevated IL-1beta contributes to antibody suppression produced by stress.
AB  - Acute stressor exposure can facilitate innate immunity and suppress acquired
      immunity. The present study further characterized the potentiating effect of
      stress on innate immunity, interleukin-1beta (IL-1beta), and demonstrated that
      stress-induced potentiation of innate immunity may contribute to the stress
      induced suppression of acquired immunity. The long-term effect of stress on IL
      1beta was measured by using an ex vivo approach. Sprague-Dawley rats were
      challenged with lipopolysaccharide (LPS) in vivo, and the IL-1beta response was
      measured in vitro. Splenocytes, mesenteric lymphocytes, and peritoneal cavity
      cells had a dose- and time-dependent ex vivo IL-1beta response to LPS. Rats that
      were exposed to inescapable shock (IS, 100 1.6 mA, 5-s tail shocks, 60-s
      intertrial interval) and challenged with a submaximal dose of LPS 4 days later
      had elevated IL-1beta measured ex vivo. To test whether the acute stress-induced
      elevation in IL-1beta contributes to the long-term suppression in acquired
      immunity, IL-1beta receptors were blocked for 24 h after stress. Serum anti
      keyhole limpet hemocyanin (KLH) immunoglobulin (Ig) was measured. In addition,
      the acute elevation (2 h post-IS) of splenic IL-1beta in the absence of antigen
      was verified. Interleukin-1 receptor antagonist prevented IS-induced suppression
      in anti-KLH Ig. These data support the hypothesis that stress-induced increases
      in innate immunity (i.e., IL-1beta) may contribute to stress-induced suppression
      in acquired immunity (i.e., anti-KLH Ig).

PMID- 12070208
TI  - Using animal data to improve prediction of human decompression risk following air
      saturation dives.
AB  - To plan for any future rescue of personnel in a disabled and pressurized
      submarine, the US Navy needs a method for predicting risk of decompression
      sickness under possible scenarios for crew recovery. Such scenarios include
      direct ascent from compressed air exposures with risks too high for ethical human
      experiments. Animal data, however, with their extensive range of exposure
      pressures and incidence of decompression sickness, could improve prediction of
      high-risk human exposures. Hill equation dose-response models were fit, by using
      maximum likelihood, to 898 air-saturation, direct-ascent dives from humans, pigs,
      and rats, both individually and combined. Combining the species allowed
      estimation of one, more precise Hill equation exponent (steepness parameter),
      thus increasing the precision associated with human risk predictions. These
      predictions agreed more closely with the observed data at 2 ATA, compared with a
      current, more general, US Navy model, although the confidence limits of both
      models overlapped those of the data. However, the greatest benefit of adding
      animal data was observed after removal of the highest risk human exposures,
      requiring the models to extrapolate.

PMID- 12070209
TI  - Dynamics of microvascular oxygen pressure in the rat diaphragm.
AB  - The relative amplitudes and rates of increase of muscle blood flow (and O(2)
      delivery) and O(2) uptake responses determine the O(2) pressure within the muscle
      microvasculature (Pm(O(2))) across the rest-to-contraction transition. Skeletal
      muscle function is a primary determinant of pulmonary O(2) uptake kinetics;
      however, it has never been determined whether the dynamics of muscle Pm(O(2)) are
      faster in a highly oxidative muscle [e.g., diaphragm (Dia), citrate synthase
      activity of 39 micromol. min(-1). g(-1)] compared with less oxidative muscles
      [e.g., spinotrapezius (Spino), citrate synthase activity of 14 micromol. min(-1).
      g(-1), male Sprague-Dawley rats; Delp MD and Duan C, J Appl Physiol 80: 261-270,
      1996]. Phosphorescence quenching techniques (porphyrin dendrimer, R2) were used
      to determine Pm(O(2)) across the transition to electrically stimulated
      contractions (1 Hz) within the rat Dia. After a delay of 10.4 +/- 1.3 (SE) s at
      the beginning of Dia contractions, Pm(O(2)) decreased close to monoexponentially
      from 42 +/- 2 to 27 +/- 3 Torr (P < 0.05) with an extremely fast time constant of
      7.1 +/- 1.1 s. Thus Dia Pm(O(2)) decreased with significantly (P < 0.05) faster
      kinetics than reported previously for the Spino muscle (delay, 19.2 +/- 2.8 s;
      time constant Pm(O(2)), 21.7 +/- 2.1 s; Behnke BJ, Kindig CA, Musch TI, Koga S,
      and Poole DC, Respir Physiol 126: 53-63, 2001). With the use of two specialized
      muscles with similar fiber-type composition but widely disparate oxidative
      capacities (Delp MD and Duan C, J Appl Physiol 80: 261-270, 1996), these data
      demonstrate that Pm(O(2)) kinetics are significantly faster in the highly
      oxidative Dia compared with the low-oxidative Spino muscle and that this effect
      is not dependent on muscle fiber-type composition.

PMID- 12070210
TI  - Measurement of gluconeogenesis in exercising men by mass isotopomer distribution
      analysis.
AB  - We evaluated the hypothesis that coordinated adjustments in absolute rates of
      gluconeogenesis (GNG(ab)) and hepatic glycogenolysis (Gly) would maintain
      euglycemia and match glucose production (GP) to peripheral utilization during
      rest and exercise. Specifically, we evaluated the extent to which gradations in
      exercise power output would affect the contribution of GNG(ab) to GP. For these
      purposes, we employed mass isotopomer distribution analysis (MIDA) and isotope
      dilution techniques on eight postabsorptive (PA) endurance-trained men during 90
      min of leg cycle ergometry at 45 and 65% peak O(2) consumption (VO(2 peak);
      moderate and hard intensities, respectively) and the preceding rest period. GP
      was constant in resting subjects, whereas the fraction from GNG (f(GNG))
      increased over time during rest (22.3 +/- 0.9% at 11.25 h PA vs. 25.6 +/- 0.9% at
      12.0 h PA, P < 0.05). In the transition from rest to exercise, GP increased in an
      intensity-dependent manner (rest, 2.0 +/- 0.1; 45%, 4.0 +/- 0.4; 65%, 5.84 +/-
      0.64 mg. kg(-1). min(-1), P < 0.05), although glucose rate of disappearance
      exceeded rate of appearance during the last 30 min of exercise at 65% VO(2 peak).
      Compared with rest, increases in GP were sustained by 92 and 135% increments in
      GNG(ab) during moderate- and hard-intensity exercises, respectively.
      Correspondingly, Gly (calculated as the difference between GP and MIDA-measured
      GNG(ab)) increased 100 and 203% over rest during the two exercise intensities.
      During moderate-intensity exercise, f(GNG) was the same as at rest; however,
      during the harder exercise f(GNG) decreased significantly to account for only 21%
      of GP. The highest sustained GNG(ab) observed in these trials on PA men was 1.24
      +/- 0.3 mg. kg(-1). min(-1). We conclude that, after an overnight fast, 1)
      absolute GNG rates increased with intensity of effort despite a reduced f(GNG) at
      65% VO(2 peak), 2) during exercise Gly is more responsible than GNG(ab) for
      maintaining GP, and 3) in 12-h fasted men, neither increased Gly or GNG(ab) nor
      was their combination able to maintain euglycemia during prolonged hard (65% VO(2
      peak)) exercise.

PMID- 12070211
TI  - Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic
      steroid administration.
AB  - Skeletal muscle is a target of anabolic steroid action; however, anabolic
      steroid's affect on aged skeletal muscle is not well understood. The effect of 4
      wk of nandrolone decanoate (ND) administration on hindlimb muscles of 5- and 25
      mo-old Fischer 344/Brown Norway rats was examined. ND (6 mg/kg body wt) was
      injected every 7th day for 4 wk. Controls received an oil injection. ND
      significantly reduced 25-mo-old rat perirenal fat pad mass by 30%. Soleus (Sol)
      and plantaris (Plan) muscle-to-body weight ratios were reduced in 25-mo-old rats.
      ND did not affect Sol or Plan muscle-to-body weight ratios at either age. Sol DNA
      concentration was reduced by 25% in 25-mo-old rats, and ND increased it to 12%
      greater than 5-mo-old rats. ND did not affect Plan DNA content. Sol androgen
      receptor (AR) protein in 25-mo-old rats was reduced to 35% of 5-mo-old values. ND
      increased AR protein by 900% in 25-mo-old rat Sol. Plan AR concentration was not
      affected by aging but was induced by ND in both age groups. Aging or ND treatment
      did not affect glucocorticoid receptor levels in either muscle. These data
      demonstrate that fast- and slow-twitch rat hindlimb muscles differ in their
      response to aging and ND therapy.

PMID- 12070212
TI  - Neutral and DEAE dextrans as tracers for assessing lung microvascular barrier
      permeability and integrity.
AB  - Steady-state lymph-to-plasma concentration ratios (L/Ps) of neutral dextrans,
      cationic DEAE dextrans, and endogenous proteins were determined under normal and
      increased permeability conditions in six unanesthetized yearling sheep prepared
      with chronic lung lymph fistulas. Fluorescent dextrans with radii ranging from 1
      to 30 nm were intravenously infused, and after 24 h, perilla ketone (PK) was
      given to alter permeability while the dextran infusion was maintained. Plasma and
      lymph samples were collected before and after PK administration and analyzed for
      dextran and protein concentrations after high-performance liquid chromatography
      size separation. Under both baseline and increased permeability conditions, DEAE
      dextrans had higher L/Ps than neutral dextrans of similar size but lower L/Ps
      than proteins of similar size. Comparison of L/Ps before and after PK revealed
      that the percentage change in permeability for neutral and DEAE dextrans was
      significantly larger than that for proteins. These results suggest that 1) the
      pulmonary microvascular barrier behaves as a net negative barrier, 2) some
      transport mechanisms for proteins and dextrans are different, and 3) neutral and
      cationic dextrans are more sensitive markers than proteins of the same size for
      assessing changes in pulmonary capillary permeability.

PMID- 12070213
TI  - Airway and tissue mechanics in a murine model of asthma: alveolar capsule vs.
      forced oscillations.
AB  - To better address the functional consequences of inflammation on bronchial
      responsiveness, we studied two groups of BALB/c mice: a nonimmunized control
      group (n = 8) and a group immunized and challenged with inhaled ovalbumin (n =
      8). An alveolar capsule (AC) measured airway resistance (Raw(AC)) and lung
      elastance (EL). A forced oscillation (FO) technique independently estimated
      airway resistance (Raw(FO)) and a parameter H(ti) related to tissue elastance.
      Ovalbumin-immunized and -challenged mice had increased numbers of eosinophils in
      bronchoalveolar lavage and increased responsiveness to methacholine (MCh).
      Corresponding parameters from the AC and FO techniques were correlated: Raw(AC)
      vs. Raw(FO) (r = 0.76) and EL vs. H(ti) (r = 0.88, P < 0.0001 in all cases). AC
      and FO techniques showed significant increases in tissue elastance in response to
      MCh but no significant increases in airway resistance. These results demonstrated
      that the AC and FO techniques yield essentially equivalent results in mice, even
      when the lung is inhomogeneous, and that the bronchoconstrictive responses to MCh
      and inflammation in mice are predominantly located in the lung periphery.

PMID- 12070214
TI  - Role of the autonomic nervous system in the reduced maximal cardiac output at
      altitude.
AB  - After acclimatization to high altitude, maximal exercise cardiac output (QT) is
      reduced. Possible contributing factors include 1) blood volume depletion, 2)
      increased blood viscosity, 3) myocardial hypoxia, 4) altered autonomic nervous
      system (ANS) function affecting maximal heart rate (HR), and 5) reduced flow
      demand from reduced muscle work capability. We tested the role of the ANS
      reduction of HR in this phenomenon in five normal subjects by separately blocking
      the sympathetic and parasympathetic arms of the ANS during maximal exercise after
      2-wk acclimatization at 3,800 m to alter maximal HR. We used intravenous doses of
      8.0 mg of propranolol and 0.8 mg of glycopyrrolate, respectively. At altitude,
      peak HR was 170 +/- 6 beats/min, reduced from 186 +/- 3 beats/min (P = 0.012) at
      sea level. Propranolol further reduced peak HR to 139 +/- 2 beats/min (P =
      0.001), whereas glycopyrrolate increased peak HR to sea level values, 184 +/- 3
      beats/min, confirming adequate dosing with each drug. In contrast, peak O(2)
      consumption, work rate, and QT were similar at altitude under all drug treatments
      [peak QT = 16.2 +/- 1.2 (control), 15.5 +/- 1.3 (propranolol), and 16.2 +/- 1.1
      l/min (glycopyrrolate)]. All QT results at altitude were lower than those at sea
      level (20.0 +/- 1.8 l/min in air). Therefore, this study suggests that, whereas
      the ANS may affect HR at altitude, peak QT is unaffected by ANS blockade. We
      conclude that the effect of altered ANS function on HR is not the cause of the
      reduced maximal QT at altitude.

PMID- 12070215
TI  - Altered frequency responses of sympathetic nerve discharge bursts after IL-1beta
      and mild hypothermia.
AB  - Although interleukin-1beta (IL-1beta) administration produces nonuniform changes
      in the level of sympathetic nerve discharge (SND), the effect of IL-1beta on the
      frequency-domain relationships between discharges in different sympathetic nerves
      is not known. Autospectral and coherence analyses were used to determine the
      effect of IL-1beta and mild hypothermia (60 min after IL-1beta, colonic
      temperature from 38 degrees C to 36 degrees C) on the relationships between renal
      interscapular brown adipose tissue (IBAT) and splenic-lumbar sympathetic nerve
      discharges in chloralose-anesthetized rats. The following observations were made.
      1) IL-1beta did not alter renal-IBAT coherence values in the 0- to 2-Hz frequency
      band or at the cardiac frequency (CF). 2) Peak coherence values relating splenic
      lumbar discharges at the CF were significantly increased after IL-1beta and
      during hypothermia. 3) Hypothermia after IL-1beta significantly reduced the
      coupling (0-2 Hz and CF) between renal-IBAT but not splenic-lumbar SND bursts. 4)
      Combining IL-1beta and mild hypothermia had a greater effect on renal-IBAT SND
      coherence values than did mild hypothermia alone. These data demonstrate
      functional plasticity in sympathetic neural circuits and suggest complex
      relationships between immune products and SND regulation.

PMID- 12070216
TI  - Hog barn dust extract stimulates IL-8 and IL-6 release in human bronchial
      epithelial cells via PKC activation.
AB  - Hog barn workers have an increased incidence of respiratory tract symptoms and
      demonstrate an increase in lung inflammatory mediators, including interleukin
      (IL)-8 and IL-6. Utilizing direct kinase assays for protein kinase C (PKC)
      activation, we demonstrated that dust from hog confinement facilities, or hog
      dust extract (HDE), augments PKC activity of human airway epithelial cells in
      vitro. A 5% dilution of HDE typically stimulates an approximately twofold
      increase in human bronchial epithelial cell (HBEC) PKC activity compared with
      control medium-treated cells. This increase in PKC is observed with 15 min of HDE
      treatment, and kinase activity reaches peak activity by 1-2 h of HDE treatment
      before returning to baseline PKC levels between 6 and 24 h. The classic PKC
      inhibitor, calphostin C, blocks HDE-stimulated PKC activity and associated IL-8
      and IL-6 release. Desensitization to HDE stimulation of PKC activation does not
      appear to occur because subsequent exposures to HDE after an initial exposure
      result in further augmentation of PKC. Detoxification of HDE with polymyxin B to
      remove endotoxin did not change PKC activation or IL-8 release, suggesting that
      endotoxin is not solely responsible for HDE augmentation of PKC. These data
      support the hypothesis that HDE exposure augments HBEC IL-8 and IL-6 release via
      a PKC-dependent pathway.

PMID- 12070217
TI  - Mechanisms of sympathoexcitation: single-unit analysis of muscle vasoconstrictor
      neurons in awake OSAS subjects.
AB  - In congestive heart failure (CHF), muscle sympathetic activity (MSNA) is greatly
      elevated, but our laboratory has shown that single muscle vasoconstrictor neurons
      primarily fire only once per cardiac interval, as in normal subjects (Elam M and
      Macefield VG. J Appl Physiol 91: 717-724, 2001; Macefield VG, Rundqvist B,
      Sverrisdottir YB, Wallin BG, and Elam M. Circulation 100: 1708-1713, 1999). In
      this study, we used patients with obstructive sleep apnea syndrome (OSAS) to test
      the hypothesis that this firing pattern is maintained in other states of
      sympathoexcitation. Unitary recordings were made from muscle vasoconstrictor
      neurons in eight awake OSAS patients. The average firing frequency of 12 units
      was 0.96 Hz and the firing probability 51%, similar to previous observations in
      CHF patients (0.98 Hz, 55%) but higher than in healthy subjects (0.40 Hz, 31%).
      However, the percentages of cardiac intervals in which neurons generated one,
      two, three, or four spikes were 59, 27, 10, and 3% in OSAS, compared with 71, 18,
      7, and 2% in CHF and 73, 18, 5, and 3% in healthy subjects. Thus the firing
      pattern is different in OSAS and CHF, leading to rejection of the hypothesis:
      although in both conditions individual neurons show an increase in firing
      probability, in OSAS patients they also fire more often within a cardiac
      interval. It is likely that differences may also be apparent in other states of
      sympathoexcitation.

PMID- 12070218
TI  - Segmental analysis of nasal cavity compliance by acoustic rhinometry.
AB  - To explore the determinants of possible collapse of the nasal valve region, a
      common cause of nasal obstruction, we evaluated the mechanical properties of the
      nasal wall. In this study, we determined the nasal cross-sectional area-to
      negative pressure ratio (nasal wall compliance) in the anterior part of the nose
      in six healthy subjects by measuring nasal area by acoustic rhinometry at
      pressures ranging from atmospheric pressure to a negative pressure of -10
      cmH(2)O. Measurements were performed at baseline and after nasal mucosal
      decongestion (oxymetazoline). At baseline, nasal wall compliance increased
      progressively from the nasal valve (0.031 +/- 0.016 cm2/cmH(2)O, mean +/- SD) to
      the anterior and medial part of the inferior turbinate (0.045 +/- 0.024
      cm2/cmH(2)O) and to the middle meatus region (0.056 +/- 0.029 cm2/cmH(2)O). After
      decongestant, compliances decreased and became similar in the three regions. On
      the basis of these results, we hypothesize that compliance of the nasal wall is
      partly related to mucosal blood volume and quantity of vascular tissue, which
      differ in the three regions, increasing from the nasal valve to the middle
      meatus.

PMID- 12070219
TI  - Developmental differences in pulmonary eNOS expression in response to chronic
      hypoxia in the rat.
AB  - Chronic hypoxia (CH) increases pulmonary endothelial nitric oxide synthase (eNOS)
      protein levels in adult rats but decreases eNOS protein levels in neonatal pigs.
      We hypothesized that this differing response to CH is due to developmental rather
      than species differences. Adult and neonatal rats were placed in either hypobaric
      hypoxia or normoxia for 2 wk. At that time, body weight, hematocrit, plasma
      nitrite/nitrate (NOx(-)), and right ventricular and total ventricular heart
      weights were measured. Percent pulmonary arterial wall area of 20-50 and 51-100
      microm arteries were also determined. Total lung protein extracts were assayed
      for eNOS levels by using immunoblot analysis. Compared with their respective
      normoxic controls, both adult and neonatal hypoxic groups demonstrated
      significantly decreased body weight, elevated hematocrit, and elevated right
      ventricular-to-total ventricular weight ratios. Both adult and neonatal hypoxic
      groups also demonstrated significantly larger percent pulmonary arterial wall
      area compared with their respective normoxic controls. Hypoxic adult pulmonary
      eNOS protein and plasma NOx(-) were significantly greater than levels found in
      normoxic adults. In contrast, hypoxic neonatal pulmonary eNOS protein and plasma
      NOx(-) were significantly less compared with normoxic neonates. We conclude that
      there is a developmental difference in eNOS expression and nitric oxide
      production in response to CH.

PMID- 12070220
TI  - Influence of acidosis and hypoxia on liver ischemia and reperfusion injury in an
      in vivo rat model.
AB  - The contribution of acidosis to the development of reperfusion injury is
      controversial. In this study, we examined the effects of respiratory acidosis and
      hypoxia in a frequently used in vivo liver ischemia and reperfusion (I/R) injury
      rat model. Rats were anesthetized with intraperitoneal anesthetics and subjected
      to partial liver ischemia (70%) for 60 min and subsequent reperfusion for 90 min
      under the following conditions: 1) no acidosis and normoxia, maintained by
      controlled ventilation; 2) acidosis and normoxia, maintained by passive supply
      with oxygen; 3) no acidosis and hypoxia, maintained by bicarbonate administration
      without respiratory support; and 4) acidosis and hypoxia, i.e., without
      respiratory support or pH correction. Changes in plasma aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured as
      parameters of hepatocellular injury, and bile secretion was monitored. AST and
      ALT levels were lowest in the ventilated rats and highest in the bicarbonate
      treated rats. No differences in bile secretion were found between groups. Our
      results suggest that respiratory acidosis significantly enhanced liver I/R injury
      under normoxic conditions, whereas respiratory acidosis significantly reduced
      liver I/R injury under hypoxic conditions.

PMID- 12070221
TI  - Assessment of functional series elastic stiffness of human dorsiflexors with fast
      controlled releases.
AB  - The series elastic stiffness (SES) of the human dorsiflexors was investigated in
      vivo with the fast controlled release method in 8 subjects. The maximum moment of
      a voluntary contraction (66 +/- 17 Nm) was significantly higher than the maximum
      moment with electrical stimulation of tibialis anterior (34 +/- 16 Nm). At an
      ankle moment of 34 Nm produced with either voluntary or electrical stimulation,
      we found a significantly different SES of 219 +/- 54 and 149 +/- 54 Nm. rad(-1),
      respectively. It is proposed that this is due to the fact that, during voluntary
      contraction, more elastic tissue parallel with each other is involved, because of
      coactivation of the extensor hallucis longus, extensor digitorum longus, and
      tibialis anterior. This shows that, for a functional assessment of the SES of the
      dorsiflexors, one has to include the toe extensors, which is possible with the
      fast controlled release method. Additionally, our results demonstrated that the
      SES of the human dorsiflexors at moment levels up to about isometric maximum did
      not reach an asymptote at which the stiffness is independent of moment, i.e., the
      series elastic component of the dorsiflexors is during daily activities loaded
      for the greatest part in the nonlinear part of the stress-strain function.

PMID- 12070222
TI  - CYP4A mRNA, protein, and product in rat lungs: novel localization in vascular
      endothelium.
AB  - The vasodilatory effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on lung
      arteries is opposite to the constrictor effect seen in cerebral and renal
      vessels. These observations raise questions about the cellular localization of 20
      HETE-forming isoforms in pulmonary arteries and other tissues. Using in situ
      hybridization, we demonstrate for the first time CYP4A (a family of cytochrome P
      450 enzymes catalyzing formation of 20-HETE from the substrate arachidonic acid)
      mRNA in pulmonary arterial endothelial and smooth muscle cells, bronchial smooth
      muscle and bronchial epithelial cells, type I epithelial cells, and macrophages
      in adult male rat lungs. Moreover, we detect CYP4A protein in rat pulmonary
      arteries and bronchi as well as cultured endothelial cells. Finally, we identify
      endogenously formed 20-HETE by using fluorescent HPLC techniques, as well as the
      capacity to convert arachidonic acid into 20-HETE in pulmonary arteries, bronchi,
      and endothelium. These data show that 20-HETE is an endogenous product of several
      pulmonary cell types and is localized to tissues that optimally position it to
      modulate physiological functions such as smooth muscle tone or electrolyte flux.

PMID- 12070223
TI  - Murine model of gastrointestinal ischemia associated with complement-dependent
      injury.
AB  - Gastrointestinal ischemia-reperfusion (I/R) injury is often associated with
      remote tissue injury. Complement activation plays an important role in local and
      remote tissue injury associated with gastrointestinal I/R. We developed a new
      murine model of gastrointestinal I/R that has complement-dependent local and
      remote tissue injury. Twenty, but not thirty, minutes of gastrointestinal
      ischemia followed by 3 h of reperfusion induced a significant loss of intestinal
      lactate dehydrogenase that was significantly prevented by a murine anti-murine C5
      monoclonal antibody. Anti-C5 also significantly decreased neutrophil infiltration
      into the gut and lung. Gastrointestinal I/R significantly increased pulmonary
      intercellular adhesion molecule-1 mRNA and protein expression that was
      significantly inhibited by anti-C5. Pulmonary macrophage inflammatory protein-2
      mRNA was significantly induced by gastrointestinal I/R and inhibited by anti-C5
      treatment. These data demonstrate that brief periods of murine gastrointestinal
      I/R activate complement, leading to tissue injury and neutrophil accumulation.
      Anti-C5 treatment attenuates tissue injury, neutrophil recruitment, and leukocyte
      adherence molecule and chemokine expression in the mouse. This model will be well
      suited to investigate the role of complement-mediated tissue injury and gene
      expression after gastrointestinal I/R.

PMID- 12070224
TI  - Fiber capillarization relative to mitochondrial volume in diaphragm of shrew.
AB  - The objective was to examine fiber capillarization in relation to fiber
      mitochondrial volume in the highly aerobic diaphragm of the shrew, the smallest
      mammal. The diaphragms of four common shrews [Sorex araneus; body mass, 8.2 +/-
      1.3 (SE) g] and four lesser shrews (Sorex minutus, 2.6 +/- 0.1 g) were perfusion
      fixed in situ, processed for electron microscopy, and analyzed by morphometry.
      Capillary length per fiber volume was extremely high, at values of 8,008 +/-
      1,054 and 12,332 +/- 625 mm(-2) in S. araneus and S. minutus, respectively (P =
      0.012), with no difference in capillary geometry between the two species. Fiber
      mitochondrial volume density was 28.5 +/- 2.3% (S. araneus) and 36.5 +/- 1.4% (S.
      minutus; P = 0.025), yielding capillary length per milliliter mitochondria values
      (S. araneus, 27.8 +/- 1.5 km; S. minutus, 33.9 +/- 2.2 km; P = 0.06) as high as
      in the flight muscle of the hummingbird and small bats. The size of the capillary
      fiber interface (i.e., capillary surface per fiber surface ratio) per fiber
      mitochondrial volume in shrew diaphragm was also as high as in bird and bat
      flight muscles, and it was about two times greater than in rat hindlimb muscle.
      Thus, whereas fiber capillary and mitochondrial volume densities decreased with
      increased body mass in S. araneus compared with S. minutus Soricinae shrews,
      fiber capillarization per milliliter mitochondria in both species was much higher
      than previously reported for shrew diaphragm, and it matched that of the
      intensely aerobic flight muscles of birds and mammals.

PMID- 12070225
TI  - Unilateral lower limb suspension does not mimic bed rest or spaceflight effects
      on human muscle fiber function.
AB  - We used Ca2+-activated skinned muscle fibers to test the hypothesis that
      unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle
      contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects
      before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of
      reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy
      chain (MHC) showed significant reductions in diameter, absolute and specific peak
      Ca2+-activated force, unloaded shortening velocity, and absolute and normalized
      peak power. Fibers obtained from the gastrocnemius were less affected by ULLS,
      particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced
      less absolute and specific peak force than did post-0 h fibers, suggesting that
      reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS
      primarily affects soleus over gastrocnemius fibers. However, in contrast to these
      other models, slow soleus fibers obtained after ULLS showed a decrease in
      unloaded shortening velocity and a greater reduction in specific force.

PMID- 12070226
TI  - Assessment of brachial artery blood flow across the cardiac cycle: retrograde
      flows during cycle ergometry.
AB  - We describe a novel software system that utilizes automated algorithms to perform
      edge detection and wall tracking of high-resolution B-mode arterial ultrasound
      images, combined with synchronized Doppler waveform envelope analysis, to
      calculate conduit arterial blood flow (BF) across the cardiac cycle. Furthermore,
      we describe changes in brachial arterial BF to the resting forearm during
      incremental cycle ergometry in eight subjects. During exercise, peak BF during
      the cardiac cycle increased at each workload (P < 0.001), because of increased
      velocity in the presence of unaltered cross-sectional area. In contrast, mean BF
      calculated across each cardiac cycle decreased at lower workloads before
      increasing at 100 and 160 W (P < 0.001). Differences in the pattern of peak and
      mean cardiac cycle flows were due to the influence of retrograde diastolic flow,
      which had a larger impact on mean flows at lower workloads. In conclusion, BF can
      be measured with high temporal resolution across the cardiac cycle in humans.
      Resting brachial arterial flow, including retrograde flow, increases during lower
      limb exercise.

PMID- 12070227
TI  - Invited review: intracellular signaling in contracting skeletal muscle.
AB  - Physical exercise is a significant stimulus for the regulation of multiple
      metabolic and transcriptional processes in skeletal muscle. For example, exercise
      increases skeletal muscle glucose uptake, and, after exercise, there are
      increases in the rates of both glucose uptake and glycogen synthesis. A single
      bout of exercise can also induce transient changes in skeletal muscle gene
      transcription and can alter rates of protein metabolism, both of which may be
      mechanisms for chronic adaptations to repeated bouts of exercise. A central issue
      in exercise biology is to elucidate the underlying molecular signaling mechanisms
      that regulate these important metabolic and transcriptional events in skeletal
      muscle. In this review, we summarize research from the past several years that
      has demonstrated that physical exercise can regulate multiple intracellular
      signaling cascades in skeletal muscle. It is now well established that physical
      exercise or muscle contractile activity can activate three of the mitogen
      activated protein kinase signaling pathways, including the extracellular signal
      regulated kinase 1 and 2, the c-Jun NH(2)-terminal kinase, and the p38. Exercise
      can also robustly increase activity of the AMP-activated protein kinase, as well
      as several additional molecules, including glycogen synthase kinase 3, Akt, and
      the p70 S6 kinase. A fundamental goal of signaling research is to determine the
      biological consequences of exercise-induced signaling through these molecules,
      and this review also provides an update of progress in this area.

PMID- 12070228
TI  - Invited review: effect of acute exercise on insulin signaling and action in
      humans.
AB  - After a single bout of exercise, insulin action is increased in the muscles that
      were active during exercise. The increased insulin action has been shown to
      involve glucose transport, glycogen synthesis, and glycogen synthase (GS)
      activation as well as amino acid transport. A major mechanism involved in
      increased insulin stimulation of glucose uptake after exercise seems to be the
      exercise-associated decrease in muscle glycogen content. Muscle glycogen content
      also plays a pivotal role for the activity of GS and for the ability of insulin
      to increase GS activity. Insulin signaling in human skeletal muscle is activated
      by physiological insulin concentrations, but the increase in insulin action after
      exercise does not seem to be related to increased insulin signaling [insulin
      receptor tyrosine kinase activity, insulin receptor substrate-1 (IRS-1) tyrosine
      phosphorylation (RS1), IRS-1-associated phosphatidylinositol 3-kinase activity,
      Akt phosphorylation (Ser(473)), glycogen synthase kinase 3 (GSK3) phosphorylation
      (Ser(21)), and GSK3alpha activity], as measured in muscle lysates. Furthermore,
      insulin signaling is also largely unaffected by exercise itself. This, however,
      does not preclude that exercise influences insulin signaling through changes in
      the spatial arrangement of the signaling compounds or by affecting unidentified
      signaling intermediates. Finally, 5'-AMP-activated protein kinase has recently
      entered the stage as a promising player in explaining at least a part of the
      mechanism by which exercise enhances insulin action.

PMID- 12070230
TI  - Selected contribution: acute cellular and molecular responses to resistance
      exercise.
AB  - Training protocols apply sequential bouts of resistance exercise (RE) to induce
      the cellular and molecular responses necessary to produce compensatory
      hypertrophy. This study was designed to 1) define the time course of selected
      cellular and molecular responses to a single bout of RE and 2) examine the
      effects of interbout rest intervals on the summation of these responses. Rat
      muscles were exposed to RE via stimulation of the sciatic nerve in vivo.
      Stimulated and control muscles were obtained at various time points post-RE and
      analyzed via Western blot and RT-PCR. A single bout of RE increased intracellular
      signaling (i.e., phosphorylations) and expression of mRNAs for insulin-like
      growth factor-I system components and myogenic markers (e.g., cyclin D1,
      myogenin). A rest interval of 48 h between RE bouts resulted in much greater
      summation of myogenic responses than 24- or 8-h rest intervals. This experimental
      approach should be useful for studying the regulatory mechanisms that control the
      hypertrophy response. These methods could also be used to compare and contrast
      different exercise parameters (e.g., concentric vs. eccentric, etc.).

PMID- 12070231
TI  - Reliability and accuracy of biomechanical measurements of the lower extremities.
AB  - The reliability of biomechanical measurements of the lower extremities, as they
      are commonly used in podiatric practice, was quantified by means of intraclass
      correlation coefficients (ICCs). This was done not only to evaluate interrater
      and intrarater reliability but also to provide an estimate for the accuracy of
      the measurements. The measurement protocol involved 30 asymptomatic subjects and
      five raters of varying experience. Each subject was measured twice by the same
      rater, with the retest immediately following the test. The study demonstrated
      that the interrater ICCs were quite low (< or =0.51), except for the measurements
      of relaxed calcaneal stance position and forefoot varus (both 0.61 and 0.62 for
      left and right, respectively). However, the intrarater ICCs were relatively high
      (>0.8) for most raters and measurement variables. Measurement accuracy was
      moderate between raters.

PMID- 12070232
TI  - Study of clinically suspected onychomycosis in a podiatric population.
AB  - Onychomycosis, by definition, is a mycotic infection of the keratinized tissue of
      the nail plate. Although it is commonly considered to be caused by one of the
      dermatotropic fungi, a variety of other organisms have been implicated as
      etiologic agents in the disease, including some bacteria and yeasts. When it is
      caused by a fungus, any or all of three types of organisms can be involved:
      dermatophytes, yeasts, and nondermatophyte organisms. The purpose of this study
      was to identify the microorganisms found in fungal cultures of clinically
      suspected onychomycosis in the patient population of the Foot Clinics of New York
      in New York City, the largest foot clinic in the world. Of the 1,800 medical
      charts reviewed, 214 had culture results, of which 120 were positive.
      Trichophyton rubrum was the most prevalent pathogen, found in 67% of positive
      cultures. The most remarkable risk factor was age, with 80% of affected
      individuals older than 35 years. False-negatives may account for the high
      percentage (44%) of negative cultures in this study.

PMID- 12070233
TI  - Relationship between proximal articular set angle and hallux abducto valgus.
AB  - A study of radiographs from 50 males and 50 females was undertaken to determine
      whether a relationship existed between the proximal articular set angle and the
      hallux abductus angle. Gender differences in the relationship were also
      investigated. The normal range for the proximal articular set angle was -2.6
      degrees to 8.6 degrees, with a mean of 5 degrees. There was no significant
      difference in the mean values between males and females. A positive linear
      correlation between the proximal articular set angle and hallux abducto valgus
      deformity was found (R(2) = 0.52), suggesting that an increased lateral tilt of
      the metatarsal head is one of the factors that lead to hallux abducto valgus
      deformity. The relationship between proximal articular set angle and hallux
      abducto valgus deformity was similar in males and females and did not account for
      the increased hallux deformity seen in females.

PMID- 12070234
TI  - Diabetic foot wound care algorithms.
AB  - The purpose of this article is to present reference guidelines to assist
      clinicians when treating diabetic patients with foot wounds. Diabetic patients
      with limb-threatening foot ulcers often have multiple coexisting medical
      conditions that frequently become impediments to the resolution of foot wounds.
      Each foot wound is unique and its etiology is multifactorial; therefore, each
      foot wound should be managed differently. The treatment algorithm presented in
      this article is divided into three categories: Algorithm I describes the
      treatment of septic foot wounds, which may be considered true podiatric surgical
      emergencies; Algorithm II describes the treatment of ischemic foot ulcers or
      gangrene with or without underlying osteomyelitis; and Algorithm III describes
      the treatment of neuropathic foot ulcers with or without underlying
      osteomyelitis.

PMID- 12070235
TI  - Treatment of scleroderma skin ulcers using becaplermin gel and hydrocolloid
      membrane.
AB  - Skin ulcers can be very painful and detrimental in patients with systemic
      sclerosis, or systemic scleroderma. A brief review of scleroderma skin ulcers is
      presented, as well as a case study that demonstrates the effectiveness of
      becaplermin gel supplemented by oral immunosuppressive agents in the treatment of
      ulcers resulting from systemic sclerosis. The time to healing (approximately 3
      months) was comparable to that associated with the oral agents and surgical
      interventions specifically designed to help heal scleroderma ulcers. Except for
      incisional biopsy, no surgical procedures were performed.

PMID- 12070236
TI  - Achilles tendon rupture as a result of oral steroid therapy.
AB  - Spontaneous Achilles tendon rupture associated with long-term oral steroid use is
      not uncommon, particularly in older patients who use these drugs daily to treat
      systemic diseases. Rupture often results in a large defect, which complicates
      surgical repair. The authors review Achilles tendon rupture associated with
      systemic and local steroid use and present a case of rupture due to chronic oral
      steroid use in a patient with Addison's disease.

PMID- 12070237
TI  - The association of hallux limitus with the accessory navicular.
AB  - Hallux limitus is one of the most prevalent, debilitating disorders of the first
      metatarsophalangeal joint, and it has many proposed etiologies. This article
      reviews these etiologies, focusing primarily on the pes planus foot. The pes
      planus foot type is often associated with symptomatic hallux limitus and the
      accessory navicular. This article discusses this correlation, although a causal
      relationship has not been proven. The prevalence and classification of the
      accessory navicular are also discussed. Clinical cases involving symptomatic
      hallux limitus occurring concomitantly with an accessory navicular are reviewed,
      including radiographic findings, symptoms, and surgical treatment.

PMID- 12070238
TI  - Prolotherapy in the treatment of foot problems.

PMID- 12070239
TI  - Idiopathic Flat-top Talus.

PMID- 12070240
TI  - Milestones in podiatric surgery.

PMID- 12070241
TI  - The p63 gene in EEC and other syndromes.
AB  - Several autosomal dominantly inherited human syndromes have recently been shown
      to result from mutations in the p63 gene. These syndromes have various
      combinations of limb malformations fitting the split hand-split foot spectrum,
      orofacial clefting, and ectodermal dysplasia. The p63 syndrome family includes
      the EEC syndrome, AEC syndrome, ADULT syndrome, limb-mammary syndrome, and non
      syndromic split hand/foot malformation. The pattern of heterozygous mutations is
      distinct for each of these syndromes. The functional effects on the p63 proteins
      also vary between syndromes. In all of these syndromes, the mutation appears to
      have both dominant negative and gain of function effects rather than causing a
      simple loss of function.

PMID- 12070242
TI  - Testing for osteogenesis imperfecta in cases of suspected non-accidental injury.
AB  - To evaluate if laboratory testing for osteogenesis imperfecta (OI) identifies
      children unrecognised by clinical examination in instances where non-accidental
      injury (NAI) is suspected as the likely cause of fracture, we carried out a
      retrospective review of available medical records and biochemical test results
      from 262 patients. Cultured fibroblasts were received for biochemical testing for
      OI from children in whom the diagnosis of NAI was suspected. Eleven of the
      samples had alterations in the amount or structure of type I collagen
      synthesised, consistent with the diagnosis of OI, and in 11 others we could not
      exclude OI. Referring physicians correctly identified children with OI in six of
      the 11 instances established by biochemical studies, did not identify OI by
      clinical examination in three, and there was inadequate clinical information to
      know in two others. Biochemical testing was inconclusive in 11 infants in whom
      the diagnosis of OI could not be excluded, none of whom were thought to be
      affected by the referring clinicians. Four children believed to have OI by
      clinical examination had normal biochemical studies, a false positive clinical
      diagnosis attributed, in large part, to the use of scleral hue (a feature that is
      age dependent) as a major diagnostic criterion. Given the inability to identify
      all children with OI by clinical examination in situations of suspected NAI,
      laboratory testing for OI (and other genetic predispositions for fractures) is a
      valuable adjunct in discerning the basis for fractures and may identify a small
      group of children with previously undiagnosed OI.

PMID- 12070243
TI  - Genetic mapping of a susceptibility locus for disc herniation and spastic
      paraplegia on 6q23.3-q24.1.
AB  - It has been suggested that a genetic factor(s) or a familial predisposition may
      contribute to the clinical manifestations of disc herniation; moreover, no
      genetic linkage between spinal disc herniation and spastic paraplegia has ever
      been described. A family with consanguineous parents and four of eight sibs
      affected by multiple disc herniations and spastic paraplegia was clinically and
      genetically analysed. Surgery caused partial improvement in all of them. After
      the exclusion of type II collagen and vitamin D receptor genes and the recessive
      loci for HSPs, a genome wide search was performed with about 500 fluorescent
      markers. Positive lod score values were obtained for chromosome 6q22.31-q24.1,
      with evidence of three homozygous intervals. The maximum multipoint lod score of
      3.28 was obtained in only one interval, between markers D6S1699 and D6S314. On
      the whole, a susceptibility locus for disc herniation and autosomal recessive
      spastic paraplegia was found on chromosome 6q23.3-q24.1. This is the first time
      that disc herniation and the associated neurological syndrome has been linked to
      a human chromosomal region.

PMID- 12070246
TI  - Association of an interleukin 1B gene polymorphism (-511) with Parkinson's
      disease in Finnish patients.

PMID- 12070244
TI  - A cryptic deletion of 2q35 including part of the PAX3 gene detected by breakpoint
      mapping in a child with autism and a de novo 2;8 translocation.
AB  - We report a de novo, apparently balanced (2;8)(q35;q21.2) translocation in a boy
      with developmental delay and autism. Cross species (colour) paint (Rx) and SKY
      FISH, forward and reverse chromosome painting, and FISH with subtelomeric probes
      were used to examine the patient's karyotype, but further rearrangements were not
      detected. FISH with region specific clones mapping near 2q35 and 8q21.2
      breakpoints and STS mapping performed on the isolated derivative chromosomes were
      used to refine the location of the breakpoints further. A cryptic deletion of
      between 4.23 and 4.41 Mb in extent and involving at least 13 complete genes or
      transcription units was found at the breakpoint on 2q35. The deletion includes
      the promoter and 5' untranslated region of the paired box 3 (PAX3) gene. The
      child has very mild dystopia canthorum which may be associated with the PAX3
      haploinsufficiency. The 8q21.2 breakpoint is within MMP16 which encodes matrix
      metalloproteinase 16. We postulate that the cryptic deletion and rearrangement
      are responsible for the patient's phenotype and that a gene (or genes)
      responsible for autism lies at 2q35 or 8q21.2. The results present a step towards
      identifying genes predisposing to autism.

PMID- 12070247
TI  - An investigation of ACE as a risk factor for dementia and cognitive decline in
      the general population.

PMID- 12070248
TI  - Change in the penetrance of founder BRCA1/2 mutations? A retrospective cohort
      study.

PMID- 12070250
TI  - What do women really want to know? Motives for attending familial breast cancer
      clinics.

PMID- 12070251
TI  - Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome.

PMID- 12070253
TI  - Mutation screening of the PKD1 transcript by RT-PCR.

PMID- 12070254
TI  - A novel 2 bp deletion in the TM4SF2 gene is associated with MRX58.

PMID- 12070255
TI  - Chromosome 2 aberrations in clinical cases characterised by high resolution
      multicolour banding and region specific FISH probes.

PMID- 12070256
TI  - Towards a suggestive facial dysmorphism in adenylosuccinate lyase deficiency?

PMID- 12070257
TI  - Prenatal detection of cystic fibrosis by ultrasonography: a retrospective study
      of more than 346 000 pregnancies.

PMID- 12070258
TI  - Attitudes of deaf and hard of hearing subjects towards genetic testing and
      prenatal diagnosis of hearing loss.

PMID- 12070259
TI  - A new case of Yq microdeletion transmitted from a normal father to two infertile
      sons.

PMID- 12070260
TI  - Klinefelter-like phenotype and primary infertility in a male with a paracentric
      Xq inversion.

PMID- 12070261
TI  - Mismatch repair gene analysis in Catalonian families with colorectal cancer.

PMID- 12070262
TI  - Mutation analysis in the candidate Mobius syndrome genes PGT and GATA2 on
      chromosome 3 and EGR2 on chromosome 10.

PMID- 12070263
TI  - Smith-Lemli-Opitz syndrome: carrier frequency and spectrum of DHCR7 mutations in
      Canada.

PMID- 12070264
TI  - Relationship between genotype and phenotype for the CFTR gene W846X mutation.

PMID- 12070265
TI  - SHOX point mutations and deletions in Leri-Weill dyschondrosteosis.

PMID- 12070266
TI  - Detection of pyruvate dehydrogenase E1 alpha-subunit deficiencies in females by
      immunohistochemical demonstration of mosaicism in cultured fibroblasts.
AB  - Deficiency of the E1 alpha-subunit of the pyruvate dehydrogenase (PDH) complex is
      an X-linked inborn error of metabolism and one of the major causes of lactic
      acidosis in children. Although most heterozygous females manifest symptoms of the
      disease, it is often difficult to establish the diagnosis as results based on
      measurement of total PDH activity, and E1 alpha-immunoreactive protein in patient
      fibroblasts may be ambiguous because of the variability in the pattern of X
      chromosome inactivation. We report the development of a set of monoclonal
      antibodies (MAbs) specific to four subunits of the PDH complex that can be used
      for detection of PDH E1 alpha deficiency. We also show that anti-E1 alpha and
      anti-E2 MAbs, when used in immunocytochemical analysis, can detect mosaicism in
      cell cultures from female patients in which as few as 2-5% of cells express the
      deficiency. This immunocytochemical approach, which is fast, reliable, and
      quantitative, will be particularly useful in identifying females with PDH E1
      alpha-subunit deficiency as a precursor to mutation analysis.

PMID- 12070267
TI  - Localization of urotensin-II immunoreactivity in normal human kidneys and renal
      carcinoma.
AB  - Human urotensin-II (U-II) is a cyclic 11-amino-acid residue peptide with a wide
      range of vasoactive properties dependent on the anatomic site and the species
      studied. The purpose of this study was to determine the localization of human U
      II in normal human kidneys and in renal carcinoma. Normal human kidneys (n=11)
      and eight cases of clear-cell carcinoma were immunostained with a polyclonal
      antibody to human U-II. In normal human kidneys, U-II was mostly present in the
      epithelial cells of tubules and ducts, with greater intensity in the distal
      convoluted tubules. Moderate U-II immunoreactivity was seen in the endothelial
      cells of renal capillaries, but only focal immunoreactivity was found in the
      endothelial cells of the glomeruli. No staining was found in the veins. All
      tumors expressed moderate U-II immunoreactivity in the cancer cells and
      vasculature. Here we demonstrate abundant expression of U-II in normal human
      kidneys and renal carcinoma. These findings suggest that the vasoactive and
      growth-mediator peptide U-II may contribute to the pathophysiology of the human
      renal system.

PMID- 12070268
TI  - Estimation of the total number of cholinergic neurons containing estrogen
      receptor-alpha in the rat basal forebrain.
AB  - This study was undertaken to estimate the total number of cholinergic cells and
      the percentage of cholinergic cells that contain estrogen receptor-alpha (ER
      alpha) in the rat basal forebrain. Double immunostaining for choline
      acetyltransferase (ChAT) and ER alpha was carried out on 50-microm-thick free
      floating sections. Because routine mounting method causes considerable flattening
      of the sections, we embedded immunostained sections in Durcupan, an epoxy resin
      known to cause virtually no shrinkage. When this procedure was used the section
      thickness was well preserved, individual cells could be clearly identified, and
      subcellular localization of ER alpha immunoreactivity was easy to verify. Cell
      counting in these sections revealed that the rat basal forebrain contains 26,390
      +/- 1097 (mean +/- SEM) cholinergic neurons. This comprises 9674 +/- 504 in the
      medial septum-vertical diagonal band of Broca, 9403 +/- 484 in the horizontal
      diagonal band of Broca, and 7312 +/- 281 in the nucleus basalis. In these nuclei,
      60%, 46%, and 14% of the cholinergic neurons were co-localized with ER alpha,
      respectively. We believe that our results are an improvement on existing data
      because of the better distinction of individual neurons that the Durcupan
      embedding method brings.

PMID- 12070269
TI  - Immunocytochemical localization of prohormone convertases PC1 and PC2 in the
      mouse thyroid gland and respiratory tract.
AB  - We examined immunocytochemical localization of the prohormone convertases, PC1
      and PC2, in the thyroid gland and respiratory tract of the adult mouse using the
      indirect enzyme- and immunogold-labeled antibody methods for light and electron
      microscopy, respectively. In the thyroid gland, PC1- and/or PC2-immunoreactive
      cells were cuboidal, scattered in the follicular epithelium and in the
      interfollicular spaces. When serial sections were immunostained with anti
      calcitonin, anti-PC1, anti-calcitonin-gene-related-peptide (CGRP), and anti-PC2
      sera, respectively, localization of both PC1 and PC2 was restricted to the
      calcitonin/CGRP-producing parafollicular cells. In the respiratory tract, only
      PC1 immunoreactivity was observed in the basal granulated neuroendocrine cells,
      which were scattered in the tracheal epithelium. Consecutive sections
      immunostained with anti-PC1 and anti-CGRP sera showed that a subpopulation of
      these PC1-immunoreactive cells contained CGRP. Double immunogold electron
      microscopy of the thyroid parafollicular cells revealed that calcitonin- and/or
      CGRP-immunopositive secretory granules were also labeled with both PC1 and PC2.
      These findings suggest that procalcitonin is proteolytically cleaved by PC2 alone
      or by PC2 together with PC1, and that the proCGRP is cleaved by PC1.

PMID- 12070270
TI  - Immunodetection of osteopontin at sites of resorption in the pulp of rat molars.
AB  - Osteopontin (OPN) has been proposed to act as a substrate for osteoclast adhesion
      during bone resorption. The aim of the present study was to examine the presence
      and distribution of OPN at sites of resorption in traumatized radicular pulp. The
      upper first molars of 6-week-old male Sprague-Dawley rats were luxated and then
      repositioned in the original sockets. The animals were sacrificed by intracardiac
      perfusion at 10 and 14 days after tooth reimplantation. The teeth were
      decalcified in EDTA and then processed for embedding in paraffin for
      histochemistry or LR White resin for immunocytochemistry. Odontoclasts were
      identified by their multinucleated morphology and expression of tartrate
      resistant acid phosphatase (TRAP). Osteopontin was immunolocalized using
      postembedding colloidal gold labeling with a chicken egg yolk anti-rat OPN
      antibody. After reimplantation of the teeth, TRAP-positive cells were present
      along the pulp dentin wall. Osteopontin was not consistently detected at exposed
      predentin/dentin surfaces. However, gold particles were often found at the margin
      of resorption lacunae. Labeling was also seen over the Golgi region and
      cytoplasmic vesicles of odontoclasts and of neutrophils and fibroblast-like
      cells. The results suggest that accumulation of OPN at the predentin/dentin
      surface is not a prerequisite for adhesion of odontoclasts to the wall substance
      and that recruited odontoclasts produce OPN locally to mediate cell and/or matrix
      events within the resorption lacuna.

PMID- 12070271
TI  - Induction of cyclo-oxygenase-2 expression in naturally occurring gastric ulcers.
AB  - Cyclo-oxygenase-2 (COX-2) is believed to participate in the repair of gastric
      ulcer. Like humans, pigs frequently develop gastric ulcers and thus represent an
      attractive animal model in which to study the repair process of naturally
      occurring gastric ulcers. However, expression of COX in the pig stomach has not
      been reported. The objectives of this study were to determine whether COX
      isoenzymes are expressed in porcine gastric ulcers and to characterize the
      porcine COX-2 cDNA. Normal stomachs (n=5) and those with gastric ulcers (n=35)
      were studied by immunohistochemistry and immunoblotting analysis. Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to isolate the complete
      porcine COX-2 cDNA. COX-1 staining was present in normal stomach and in ulcerated
      areas. No COX-2 was detected in normal stomach, but COX-2 was strongly expressed
      in the ulcerated area in 28/35 (80%) gastric ulcers (p<0.01). Immunoblotting
      analysis confirmed the restricted expression of COX-2 in the ulcerated areas. The
      porcine COX-2 cDNA was shown to code for a 604 amino acid protein that is 89%
      identical to human COX-2. These results provide the complete primary structure of
      porcine COX-2 and demonstrate for the first time that the enzyme is induced in
      naturally occurring porcine gastric ulcers.

PMID- 12070272
TI  - Upregulation of VEGF-A without angiogenesis in a mouse model of dilated
      cardiomyopathy caused by mitochondrial dysfunction.
AB  - Angiogenesis is implicated in a variety of human pathologies and may also play a
      role in the progression of heart failure. We have studied the expression of
      members of the vascular endothelial growth factor (VEGF) and the angiopoietin
      families and their receptors in mice lacking the mitochondrial transcription
      factor A. These mice lack functional respiratory chain activity in their myocytes
      and develop dilated cardiomyopathy (DCM) postnatally. We studied the hearts of
      the knockout mice by in situ hybridization, Western blotting analysis, and
      immunohistochemistry. VEGF-A mRNA and protein levels were elevated in the
      myocardium of the knockouts. Levels of the hypoxia inducible transcription factor
      1 alpha (HIF1 alpha) and of glyceraldehyde-3-phosphate dehydrogenase transcripts
      were also increased, whereas those of angiopoietin-1 and -2 were reduced. Despite
      the striking upregulation of VEGF-A, there was no increase in capillary density
      in the knockout hearts. This study suggests that a disturbance in angiogenesis
      may contribute to the pathogenesis of DCM.

PMID- 12070273
TI  - Localization of osteoprotegerin (OPG) on bone surfaces and cement lines in rat
      tibia.
AB  - Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor (TNF)
      receptor family, is an osteoclastogenesis inhibitory factor. We investigated the
      localization of OPG in rat tibia using a specific peptide antibody to clarify the
      role of OPG in bone remodeling. OPG reactivity was mainly seen on bone surfaces.
      In bone matrices, OPG was also localized on cartilage/bone interfaces and cement
      lines. However, labeling was scarcely detected in the region of contact between
      osteoclasts and stromal cells. Some osteoblasts and osteocytes showed weak
      labeling. Immunoreactivity was not seen in chondrocytes or osteoclasts.
      Immunoelectron microscopic observation revealed that OPG is localized on the bone
      surfaces under osteoclasts. These findings suggest that OPG derived from
      osteoblast lineage cells and/or serum may be concentrated on resorbed bone
      surfaces and subsequently on cement lines. OPG may play an important role in the
      prevention of excess bone resorption by inhibiting differentiation and activity
      of osteoclasts in bone remodeling.

PMID- 12070274
TI  - An immunohistochemical study of the rabbit suprapatella, a sesamoid
      fibrocartilage in the quadriceps tendon containing aggrecan.
AB  - The rabbit suprapatella is a sesamoid fibrocartilage in the deep surface of the
      tendon of vastus intermedius and an integral part of the knee joint. We report
      the presence of a variety of proteoglycans (aggrecan and versican),
      glycosaminoglycans (chondroitin 4 and 6 sulfate, dermatan sulfate, keratan
      sulfate) and glycoproteins (tenascin) in its extracellular matrix and the
      intermediate filament vimentin in the fibrocartilage cells. The most significant
      finding is the presence of aggrecan in the extracellular matrix, along with its
      associated link protein and several of its integral glycosaminoglycans. Aggrecan
      probably enables the suprapatella to withstand compression. Although it can be
      assumed that aggrecan metabolites detected in synovial fluid from some human
      joints are predominantly associated with articular hyaline cartilage, the
      presence of aggrecan in the rabbit suprapatella means that this cannot be assumed
      for all animal knee joints. We conclude that it is important for orthopedic
      researchers who use animal models for arthritis research to check for the
      presence of a suprapatella when joint fluid analyses are interpreted.

PMID- 12070275
TI  - c-Jun-like immunoreactivity in apoptosis is the result of a crossreaction with
      neoantigenic sites exposed by caspase-3-mediated proteolysis.
AB  - Previous reports in various cells and species have shown that apoptotic cells are
      specifically and strongly labeled by certain c-Jun/N-terminal antibodies, such as
      c-Jun/sc45. This kind of immunoreactivity is confined to the cytoplasm. It is not
      due to c-Jun but appears to be related to c-Jun-like neoepitopes generated during
      apoptosis. This study was planned to gain further information about c-Jun-like
      immunostaining during apoptosis and to evaluate these antibodies as possible
      tools for characterizing cell death. Most of the experiments were performed in
      chick embryo spinal cord. When the apoptotic c-Jun-like immunoreactivity and
      caspase-3 immunostaining patterns were compared, we found that both antibodies
      immunostained the same dying cells in a similar pattern. In contrast to TUNEL
      staining, which reveals a positive reaction in both apoptotic and necrotic dying
      cells, active caspase-3 and c-Jun/sc45 antibodies are more selective because they
      stained only apoptotic cells. When cytosolic extracts from normal tissues were
      digested in vitro with caspase-3, c-Jun/sc45 immunoreactivity was strongly
      induced in several proteins, as demonstrated by Western blotting. Similar results
      were found when normal tissue sections were treated with caspase-3. Our results
      show that c-Jun/sc45 antibodies react with neoepitopes generated from cell
      proteins cleaved by activated caspases during apoptosis. We conclude that c
      Jun/sc45 antibodies may be useful for detecting apoptosis. They can even be used
      in archival paraffin-embedded tissue samples.

PMID- 12070276
TI  - Temporal and spatial expression of a novel zinc finger transcription factor,
      AJ18, in developing murine skeletal tissues.
AB  - Bone morphogenetic proteins (BMPs) are characterized by their ability to induce
      osteoblastic differentiation. However, the mechanism of osteo-induction by BMPs
      has yet to be determined. Using differential display we previously identified
      AJ18, a zinc finger transcription factor, as an immediate-early response gene to
      BMP-7. AJ18 was shown to bind to the osteoblast-specific element2 (OSE2) and to
      modulate transactivation by Runx2, a master gene in osteoblastic differentiation.
      Here we describe the temporal and spatial expression of AJ18 in developing mouse
      tissues. AJ18 mRNA expression was observed in most tissues, except liver, and was
      generally highest early in embryonic development, decreasing markedly after
      parturition. Consistent with immunohistochemical analysis, AJ18 mRNA expression
      was highest in the brain, kidney, and bone of 17 dpc (days post coitum) embryos.
      In endochondral bones of embryonic and 4-week-old mice, immunostaining for AJ18
      was strong in the nuclei of proliferating and pre-hypertrophic chondrocytes, and
      osteoblasts, whereas there was low or no staining in hypertrophic chondrocytes.
      In teeth of embryonic and 4-week-old mice, nuclear staining was observed in
      precursor and mature ameloblasts, odontoblasts, and cementoblasts, respectively.
      In addition, in 4-week-old mice staining of AJ18 was observed within alveolar
      bone cells and periodontal ligament cells. In general, the spatial expression of
      AJ18 in skeletal and non-skeletal tissues of mouse embryos showed striking
      similarity to the expression of BMP-7 mRNA. Therefore, the expression of AJ18 is
      consistent with its perceived role as a transcriptional factor that regulates
      developmental processes downstream of BMP-7.

PMID- 12070277
TI  - Cellular pathway of plasmids vectorized by cholesterol-based cationic liposomes.
AB  - We investigated by transmission electron microscopy the cellular route in tumor
      MCF7 cells of DNA labeled with digoxigenin, carried by cationic liposomes (Lip+)
      prepared from TMAEC-Chol [3 beta(N-(N',N',N'-trimethylaminoethane)
      carbamoyl)cholesterol iodide] and TEAPC-Chol [3 beta(N-(N',N',N'
      triethylaminopropane)-carbamoyl)cholesterol iodide], two cholesterol-based
      cationic lipids containing a quaternary ammonium. In a previous work we showed
      the pathway of cationic lipid/plasmid complexes from the beginning of endocytosis
      until their entry into the perinuclear area. Beyond this limit, unlabeled
      exogenous plasmids cannot be distinguished with nuclear DNA. This work dealt with
      the cellular fate of cationic liposome-vectorized plasmids labeled with
      digoxigenin using an immunogold procedure. Early after the beginning of
      transfection (30 min, 1 hr, 5 hr), gold particles were observed only in the
      cytoplasm and in endosome-like vesicles, whereas after 24 hr gold particles were
      densely present in the nucleus. These results demonstrate the nuclear
      localization of plasmids vectorized by the cationic liposomes used. The results
      are discussed in comparison with transfection efficiency measurements.

PMID- 12070278
TI  - Tissue distribution of surfactant proteins A and D in the mouse.
AB  - Surfactant proteins A and D, collagen-like lectins (collectins), were first
      isolated from the lung. In the lung, SP-A and SP-D have roles in surfactant
      homeostasis and innate immunity. In this study we show that SP-A and SP-D mRNA
      can be detected in a significant number of non-pulmonary tissues but the proteins
      have a more limited distribution. SP-D protein was detected in lung, uterus,
      ovary, and lacrimal gland, whereas SP-A protein was detected only in the lung.
      The results suggest that SP-D participates in mucosal immunity throughout the
      body.

PMID- 12070279
TI  - Cytokine requirements for acute and Basal homeostatic proliferation of naive and
      memory CD8+ T cells.
AB  - Both naive and memory T cells undergo antigen-independent proliferation after
      transfer into a T cell-depleted environment (acute homeostatic proliferation),
      whereas only memory T cells slowly divide in a full T cell compartment (basal
      proliferation). We show, first, that naive and memory CD8+ T cells have different
      cytokine requirements for acute homeostatic proliferation. Interleukin (IL)-7
      receptor(R)alpha-mediated signals were obligatory for proliferation of naive T
      cells in lymphopenic hosts, whereas IL-15 did not influence their division.
      Memory T cells, on the other hand, could use either IL-7Ralpha- or IL-15-mediated
      signals for acute homeostatic proliferation: their proliferation was delayed when
      either IL-7Ralpha was blocked or IL-15 removed, but only when both signals were
      absent was proliferation ablated. Second, the cytokine requirements for basal and
      acute homeostatic proliferation of CD8+ memory T cells differ, as basal division
      of memory T cells was blocked completely in IL-15-deficient hosts. These data
      suggest a possible mechanism for the dearth of memory CD8+ T cells in IL-15- and
      IL-15Ralpha-deficient mice is their impaired basal proliferation. Our results
      show that naive and memory T lymphocytes differ in their cytokine dependence for
      acute homeostatic proliferation and that memory T lymphocytes have distinct
      requirements for proliferation in full versus empty compartments.

PMID- 12070280
TI  - Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory
      phenotype CD8+ cells but are not required for memory phenotype CD4+ cells.
AB  - The overall size and composition of the pool of naive and memory T cells are
      tightly regulated by homeostatic mechanisms. Recent work has shown that
      homeostasis of naive T cells is controlled by two factors, self-major
      histocompatibility complex (MHC)/peptide ligands and a cytokine, interleukin (IL)
      7. In particular, contact with these two factors is required for naive CD4+ and
      CD8+ cells to undergo "homeostatic" proliferation, i.e., proliferation induced as
      a consequence of severe T cell depletion. In contrast to naive T cells, the
      factors that drive memory T cells to undergo homeostatic proliferation are poorly
      understood. To address this issue, purified memory phenotype CD4+ and CD8+ cells
      from normal mice were adoptively transferred into various gene-knockout mice
      rendered T cell-deficient by sublethal irradiation. Three findings are reported.
      First, unlike naive T cells, homeostatic proliferation of memory T cells is
      largely MHC independent. Second, memory CD8+ cells can utilize either IL-7 or IL
      15 to undergo homeostatic proliferation; however, in the absence of both IL-7 and
      IL-15, homeostatic proliferation fails to occur. Third, unlike memory CD8+ cells,
      homeostatic proliferation of memory CD4+ cells is independent of IL-7 and IL-15
      (also IL-4). Thus, the homeostatic proliferation mechanisms that control memory
      CD8+ cells and memory CD4+ cells are quite distinct.

PMID- 12070281
TI  - Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of
      memory phenotype CD8+ T cells.
AB  - Transgenic (TG) mice expressing a high copy number of interleukin (IL)-7 cDNA
      under the control of the major histocomaptability complex (MHC) class II promoter
      display a 10-20-fold increase in total T cell numbers. Here, we show that the
      increase in T cell numbers in IL-7 TG mice is most apparent at the level of
      memory phenotype CD44hi CD122hi CD8+ cells. Based on studies with T cell receptor
      (TCR) TG mice crossed to IL-7 TG mice, increased levels of IL-7 may provide
      costimulation for TCR recognition of self-MHC ligands and thus cause naive CD8+
      cells to proliferate and differentiate into memory phenotype cells. In addition,
      a marked increase in CD44hi CD122hi CD8+ cells was found in IL-7 TG IL-15(-)
      mice. Since these cell are rare in normal IL-15(-) mice, the dependency of memory
      phenotype CD8+ cells on IL-15 can be overcome by overexpression of IL-7.

PMID- 12070282
TI  - Interleukin 15 is required for proliferative renewal of virus-specific memory CD8
      T cells.
AB  - The generation and efficient maintenance of antigen-specific memory T cells is
      essential for long-lasting immunological protection. In this study, we examined
      the role of interleukin (IL)-15 in the generation and maintenance of virus
      specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15
      receptor alpha chain. Both cytokine- and receptor-deficient mice made potent
      primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus
      (LCMV), effectively cleared the virus and generated a pool of antigen-specific
      memory CD8 T cells that were phenotypically and functionally similar to memory
      CD8 T cells present in IL-15(+/+) mice. However, longitudinal analysis revealed a
      slow attrition of virus-specific memory CD8 T cells in the absence of IL-15
      signals. This loss of CD8 T cells was due to a severe defect in the proliferative
      renewal of antigen-specific memory CD8 T cells in IL-15(-/-) mice. Taken
      together, these results show that IL-15 is not essential for the generation of
      memory CD8 T cells, but is required for homeostatic proliferation to maintain
      populations of memory cells over long periods of time.

PMID- 12070283
TI  - Mesenchymal stem cells in perichondrium express activated leukocyte cell adhesion
      molecule and participate in bone marrow formation.
AB  - Perichondrium in fetal limb is composed of undifferentiated mesenchymal cells.
      However, the multipotency of cells in this region and the role of perichondrium
      in bone marrow formation are not well understood. In this report, we purified and
      characterized perichondrial cells using a monoclonal antibody against activated
      leukocyte cell adhesion molecule (ALCAM) and investigated the role of
      perichondrial cells in hematopoietic bone marrow formation. ALCAM is expressed on
      hematopoietic cells, endothelial cells, bone marrow stromal cells, and
      mesenchymal stem cells and mediates homophilic (ALCAM-ALCAM)/heterophilic (ALCAM
      CD6) cell adhesion. Here we show by immunohistochemical staining that ALCAM is
      expressed in perichondrium. ALCAM+ perichondrial cells isolated by FACS exhibit
      the characteristics of mesenchymal stem cells. ALCAM+ cells can differentiate
      into osteoblasts, adipocytes, chondrocytes, and stromal cells, which can support
      osteoclastogenesis, hematopoiesis, and angiogenesis. Furthermore, the addition of
      ALCAM-Fc or CD6-Fc to the metatarsal culture, the invasion of the blood vessels
      to a cartilage was inhibited. Our findings indicate that ALCAM+ perichondrial
      cells participate in vascular invasion by recruiting osteoclasts and vessels.
      These findings suggest that perichondrium might serve as a stem cell reservoir
      and play an important role in the early development of a bone and bone marrow.

PMID- 12070284
TI  - Vaccination with heat-killed leishmania antigen or recombinant leishmanial
      protein and CpG oligodeoxynucleotides induces long-term memory CD4+ and CD8+ T
      cell responses and protection against leishmania major infection.
AB  - CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive
      cellular immune responses. In this report, the ability of CpG ODN to confer long
      term immunity and protection when used as a vaccine adjuvant with a clinical
      grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant
      leishmanial protein was studied. In two different mouse models of L. major
      infection, vaccination with ALM plus CpG ODN was able to control infection and
      markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6
      (B6) mice, respectively, up to 12 wk after immunization. Moreover, B6 mice
      immunized with ALM plus CpG ODNs were still protected against infectious
      challenge even 6 mo after vaccination. In terms of immune correlates of
      protection, ALM plus CpG ODN-vaccinated mice displayed L. major-specific T helper
      cell 1 and CD8+ responses. In addition, complete protection was markedly
      abrogated in mice depleted of CD8+ T cells at the time of vaccination. Similarly,
      mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long
      term protection that was dependent on CD8+ T cells in vivo. Together, these data
      demonstrate that CpG ODN, when used as a vaccine adjuvant with either a
      recombinant protein or heat-killed leishmanial antigen, can induce long-term
      protection against an intracellular infection in a CD8-dependent manner.

PMID- 12070285
TI  - Active immunization against the vascular endothelial growth factor receptor flk1
      inhibits tumor angiogenesis and metastasis.
AB  - The vascular endothelial growth factor (VEGF) receptor fetal liver kinase 1
      (flk1; VEGFR-2, KDR) is an endothelial cell-specific receptor tyrosine kinase
      that mediates physiological and pathological angiogenesis. We hypothesized that
      an active immunotherapy approach targeting flk1 may inhibit tumor angiogenesis
      and metastasis. To test this hypothesis, we first evaluated whether immune
      responses to flk1 could be elicited in mice by immunization with dendritic cells
      pulsed with a soluble flk1 protein (DC-flk1). This immunization generated flk1
      specific neutralizing antibody and CD8+ cytotoxic T cell responses, breaking
      tolerance to self-flk1 antigen. Tumor-induced angiogenesis was suppressed in
      immunized mice as measured in an alginate bead assay. Development of pulmonary
      metastases was strongly inhibited in DC-flk1-immunized mice challenged with B16
      melanoma or Lewis lung carcinoma cells. DC-flk1 immunization also significantly
      prolonged the survival of mice challenged with Lewis lung tumors. Thus, an active
      immunization strategy that targets an angiogenesis-related antigen on endothelium
      can inhibit angiogenesis and may be a useful approach for treating angiogenesis
      related diseases.

PMID- 12070286
TI  - Constitutive endocytosis and degradation of the pre-T cell receptor.
AB  - The pre-T cell receptor (TCR) signals constitutively in the absence of putative
      ligands on thymic stroma and signal transduction correlates with translocation of
      the pre-TCR into glycolipid-enriched microdomains (rafts) in the plasma membrane.
      Here, we show that the pre-TCR is constitutively routed to lysosomes after
      reaching the cell surface. The cell-autonomous down-regulation of the pre-TCR
      requires activation of the src-like kinase p56(lck), actin polymerization, and
      dynamin. Constitutive signaling and degradation represents a feature of the pre
      TCR because the gammadeltaTCR expressed in the same cell line does not exhibit
      these features. This is also evident by the observation that the protein
      adaptor/ubiquitin ligase c-Cbl is phosphorylated and selectively translocated
      into rafts in pre-TCR- but not gammadeltaTCR-expressing cells. A role of c-Cbl
      mediated ubiquitination in pre-TCR degradation is supported by the reduction of
      degradation through pharmacological inhibition of the proteasome and through a
      dominant-negative c-Cbl ubiquitin ligase as well as by increased pre-TCR surface
      expression on immature thymocytes in c-Cbl-deficient mice. The pre-TCR
      internalization contributes significantly to the low surface level of the
      receptor on developing T cells, and may in fact be a requirement for optimal pre
      TCR function.

PMID- 12070288
TI  - Targeted disruption of LIGHT causes defects in costimulatory T cell activation
      and reveals cooperation with lymphotoxin beta in mesenteric lymph node genesis.
AB  - The recently described tumor necrosis factor (TNF) family member LIGHT (herpes
      virus entry mediator [HVEM]-L/TNFSF14), a ligand for the lymphotoxin (LT)beta
      receptor, HVEM, and DcR3, was inactivated in the mouse. In contrast to mice
      deficient in any other member of the LT core family, LIGHT(-/-) mice develop
      intact lymphoid organs. Interestingly, a lower percentage of LIGHT(-/-)LTbeta(-/
      ) animals contain mesenteric lymph nodes as compared with LTbeta(-/-) mice,
      whereas the splenic microarchitecture of LIGHT(-/-)LTbeta(-/-) and LTbeta(-/-)
      mice shows a comparable state of disruption. This suggests the existance of an
      additional undiscovered ligand for the LTbeta receptor (LTbetaR) or a weak
      LTalpha(3)-LTbetaR interaction in vivo involved in the formation of secondary
      lymphoid organs. LIGHT acts synergistically with CD28 in skin allograft rejection
      in vivo. The underlying mechanism was identified in in vitro allogeneic MLR
      studies, showing a reduced cytotoxic T lymphocyte activity and cytokine
      production. Detailed analyses revealed that proliferative responses specifically
      of CD8+ T cells are impaired and interleukin 2 secretion of CD4+ T cells is
      defective in the absence of LIGHT. Furthermore, a reduced 3[H]-thymidine
      incorporation after T cell receptor stimulation was observed. This for the first
      time provides in vivo evidence for a cooperative role for LIGHT and LTbeta in
      lymphoid organogenesis and indicates important costimulatory functions for LIGHT
      in T cell activation.

PMID- 12070287
TI  - Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient
      mice.
AB  - The adaptor protein Lnk, and the closely related proteins APS and SH2B, form a
      subfamily of SH2 domain-containing proteins implicated in growth factor,
      cytokine, and immunoreceptor signaling. To elucidate the physiological function
      of Lnk, we derived Lnk-deficient mice. Lnk(-/-) mice are viable, but display
      marked changes in the hematopoietic compartment, including splenomegaly and
      abnormal lymphoid and myeloid homeostasis. The in vitro proliferative capacity
      and absolute numbers of hematopoietic progenitors from Lnk(-/-) mice are greatly
      increased, in part due to hypersensitivity to several cytokines. Moreover, an
      increased synergy between stem cell factor and either interleukin (IL)-3 or IL-7
      was observed in Lnk(-/-) cells. Furthermore, Lnk inactivation causes abnormal
      modulation of IL-3 and stem cell factor-mediated signaling pathways. Consistent
      with these results, we also show that Lnk is highly expressed in multipotent
      cells and committed precursors in the erythroid, megakaryocyte, and myeloid
      lineages. These data implicate Lnk as playing an important role in hematopoiesis
      and in the regulation of growth factor and cytokine receptor-mediated signaling.

PMID- 12070289
TI  - Transepithelial migration of Toxoplasma gondii is linked to parasite motility and
      virulence.
AB  - After oral ingestion, Toxoplasma gondii crosses the intestinal epithelium,
      disseminates into the deep tissues, and traverses biological barriers such as the
      placenta and the blood-brain barrier to reach sites where it causes severe
      pathology. To examine the cellular basis of these processes, migration of T.
      gondii was studied in vitro using polarized host cell monolayers and
      extracellular matrix. Transmigration required active parasite motility and the
      highly virulent type I strains consistently exhibited a superior migratory
      capacity than the nonvirulent type II and type III strains. Type I strain
      parasites also demonstrated a greater capacity for transmigration across mouse
      intestine ex vivo, and directly penetrated into the lamina propria and vascular
      endothelium. A subpopulation of virulent type I parasites exhibited a long
      distance migration (LDM) phenotype in vitro, that was not expressed by
      nonvirulent type II and type III strains. Cloning of parasites expressing the LDM
      phenotype resulted in substantial increase of migratory capacity in vitro and in
      vivo. The potential to up-regulate migratory capacity in T. gondii likely plays
      an important role in establishing new infections and in dissemination upon
      reactivation of chronic infections.

PMID- 12070290
TI  - Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of
      cytokine release.
AB  - We recently purified lipoteichoic acid (LTA) from Staphylococcus aureus to more
      than 99% purity by a novel preparation method and deduced its structure with the
      first nuclear magnetic resonance (NMR) of a complete LTA. In contrast to Gram
      negative lipopolysaccharides, this LTA requires the toll-like receptor (TLR)-2
      and not TLR-4 for cytokine induction in monocytes and macrophages. To elucidate
      the structure-function relationships for LTA from S. aureus, the lipid anchor was
      prepared by either acidic hydrolysis of native LTA or chemical synthesis
      (gentiobiosyl-sn-dimyristoylglycerol). Next, a complete LTA molecule with six
      glycerophosphate units carrying four alanine plus one N-acetyl-glucosamine
      substituent was synthesized, which displayed the same potency to activate
      monocytes as native LTA. However, 100-1,000 times higher concentrations of the
      lipid anchor were required for cytokine induction. It is worthy to note that
      replacing D-alanine with L-alanine blunted the effect indicating stereoselective
      recognition. The structure identification of this synthesized and biologically
      active LTA was proven by NMR and matrix-assisted laser desorption-ionization mass
      spectrometry. We concluded that the lipid anchor, with its fatty acids,
      represents an integral part of the immunostimulatory activity of LTA, but
      requires additional structural components on the polyglycerophosphate backbone.

PMID- 12070291
TI  - Identification of regulatory T cells in tolerated allografts.
AB  - Induction of transplantation tolerance with certain therapeutic nondepleting
      monoclonal antibodies can lead to a robust state of peripheral "dominant"
      tolerance. Regulatory CD4+ T cells, which mediate this form of "dominant"
      tolerance, can be isolated from spleens of tolerant animals. To determine whether
      there were any extra-lymphoid sites that might harbor regulatory T cells we
      sought their presence in tolerated skin allografts and in normal skin. When
      tolerated skin grafts are retransplanted onto T cell-depleted hosts, graft
      infiltrating T cells exit the graft and recolonize the new host. These colonizing
      T cells can be shown to contain members with regulatory function, as they can
      prevent nontolerant lymphocytes from rejecting fresh skin allografts, without
      hindrance of rejection of third party skin. Our results suggest that T cell
      suppression of graft rejection is an active process that operates beyond
      secondary lymphoid tissue, and involves the persistent presence of regulatory T
      cells at the site of the tolerated transplant.

PMID- 12070292
TI  - Protein kinase C beta controls nuclear factor kappaB activation in B cells
      through selective regulation of the IkappaB kinase alpha.
AB  - Activation of the nuclear factor (NF)-kappaB transcription complex by signals
      derived from the surface expressed B cell antigen receptor controls B cell
      development, survival, and antigenic responses. Activation of NF-kappaB is
      critically dependent on serine phosphorylation of the IkappaB protein by the
      multi-component IkappaB kinase (IKK) containing two catalytic subunits (IKKalpha
      and IKKbeta) and one regulatory subunit (IKKgamma). Using mice deficient for
      protein kinase C beta (PKCbeta) we show an essential role of PKCbeta in the
      phosphorylation of IKKalpha and the subsequent activation of NF-kappaB in B
      cells. Defective IKKalpha phosphorylation correlates with impaired B cell antigen
      receptor-mediated induction of the pro-survival protein Bcl-xL. Lack of IKKalpha
      phosphorylation and defective NF-kappaB induction in the absence of PKCbeta
      explains the similarity in immunodeficiencies caused by PKCbeta or IKKalpha
      ablation in B cells. Furthermore, the well established functional cooperation
      between the protein tyrosine kinase Bruton's tyrosine kinase (Btk), which
      regulates the activity of NF-kappaB and PKCbeta, suggests PKCbeta as a likely
      serine/threonine kinase component of the Btk-dependent NF-kappaB activating
      signal transduction chain downstream of the BCR.

PMID- 12070293
TI  - Inducing tumor immunity through the selective engagement of activating Fcgamma
      receptors on dendritic cells.
AB  - Induction of tumor-specific immunity requires that dendritic cells (DCs)
      efficiently capture and present tumor antigens to result in the expansion and
      activation of tumor-specific cytotoxic T cells. The transition from antigen
      capture to T cell stimulation requires a maturation signal; in its absence
      tolerance, rather than immunity may develop. While immune complexes (ICs) are
      able to enhance antigen capture, they can be poor at inducing DC maturation,
      naive T cell activation and protective immunity. We now demonstrate that
      interfering with the inhibitory signal delivered by FcgammaRIIB on DCs converts
      ICs to potent maturation agents and results in T cell activation. Applying this
      approach to immunization with DCs pulsed ex-vivo with ICs, we have generated
      antigen-specific CD8+ T cells in vivo and achieved efficient protective immunity
      in a murine melanoma model. These data imply that ICs may normally function to
      maintain tolerance through the binding to inhibitory FcgammaRs on DCs, but they
      can be converted to potent immunogenic stimuli by selective engagement of
      activating FcgammaRs. This mechanism suggests a novel approach to the development
      of tumor vaccines.

PMID- 12070295
TI  - New directions in vaccine research.

PMID- 12070294
TI  - Multiple choices: regulation of memory CD8 T cell generation and homeostasis by
      interleukin (IL)-7 and IL-15.

PMID- 12070296
TI  - Exploiting dendritic cells to improve vaccine efficacy.

PMID- 12070297
TI  - Optimizing hematopoietic recovery following bone marrow transplantation.

PMID- 12070298
TI  - Tissue plasminogen activator and seizures: a clot-buster's secret life.

PMID- 12070299
TI  - TGF-beta antagonists: why suppress a tumor suppressor?

PMID- 12070300
TI  - Cellular sensors of feast and famine.

PMID- 12070301
TI  - Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids
      and correct lipid trafficking in Niemann-Pick C cells.
AB  - We recently showed that human skin fibroblasts internalize fluorescent analogues
      of the glycosphingolipids lactosylceramide and globoside almost exclusively by a
      clathrin-independent mechanism involving caveolae. In contrast, a sphingomyelin
      analogue is internalized approximately equally via clathrin-dependent and
      caveolar routes. Here, we further characterized the caveolar pathway for
      glycosphingolipids, showing that Golgi targeting of sphingolipids internalized
      via caveolae required microtubules and phosphoinositol 3-kinases and was
      inhibited in cells expressing dominant-negative Rab7 and Rab9 constructs. In
      addition, overexpression of wild-type Rab7 or Rab9 (but not Rab11) in Niemann
      Pick type C (NP-C) lipid storage disease fibroblasts resulted in correction of
      lipid trafficking defects, including restoration of Golgi targeting of
      fluorescent lactosylceramide and endogenous GM(1) ganglioside, and a dramatic
      reduction in intracellular cholesterol stores. Our results demonstrate a role for
      Rab7 and Rab9 in the Golgi targeting of glycosphingolipids and suggest a new
      therapeutic approach for restoring normal lipid trafficking in NP-C cells.

PMID- 12070302
TI  - Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and
      metastases.
AB  - TGF-betas are potent inhibitors of epithelial cell proliferation. However, in
      established carcinomas, autocrine/paracrine TGF-beta interactions can enhance
      tumor cell viability and progression. Thus, we studied the effect of a soluble
      Fc:TGF-beta type II receptor fusion protein (Fc:TbetaRII) on transgenic and
      transplantable models of breast cancer metastases. Systemic administration of
      Fc:TbetaRII did not alter primary mammary tumor latency in MMTV-Polyomavirus
      middle T antigen transgenic mice. However, Fc:TbetaRII increased apoptosis in
      primary tumors, while reducing tumor cell motility, intravasation, and lung
      metastases. These effects correlated with inhibition of Akt activity and FKHRL1
      phosphorylation. Fc:TbetaRII also inhibited metastases from transplanted 4T1 and
      EMT-6 mammary tumors in syngeneic BALB/c mice. Tumor microvessel density in a
      mouse dorsal skin window chamber was unaffected by Fc:TbetaRII. Therefore,
      blockade of TGF-beta signaling may reduce tumor cell viability and migratory
      potential and represents a testable therapeutic approach against metastatic
      carcinomas.

PMID- 12070303
TI  - Enhanced ERK-1/2 activation in mice susceptible to coxsackievirus-induced
      myocarditis.
AB  - Group B coxsackieviral (CVB) infection commonly causes viral myocarditis. Mice
      are protected from CVB3 myocarditis by gene-targeted knockout of p56(Lck)(Lck),
      the Src family kinase (Src) essential for T cell activation. Extracellular signal
      regulated kinase 1 and 2 (ERK-1/2) can influence cell function downstream of Lck.
      Using T cell lines and neonatal cardiac myocytes we investigated the role of ERK
      1/2 in CVB3 infection. In Jurkat T cells ERK-1/2 is rapidly activated by CVB3;
      but, this response is absent in Lck-negative JCaM T cells. Inhibition of ERK-1/2
      with UO126 reduced CVB3 titers in Jurkat cells, but not in JCaM cells. In cardiac
      myocytes CVB3 activation of ERK-1/2 is blocked by the Src inhibitor PP2. In
      addition, viral production in myocytes is decreased by Src or ERK-1/2 inhibition.
      In vitro, in both immune and myocardial cells, ERK-1/2 is activated by CVB3
      downstream of Lck and other Src's and is necessary for efficient CVB3
      replication. In vivo, following CVB3 infection, ERK-1/2 activation is evident in
      the myocardium. ERK-1/2 activation is intense in the hearts of myocarditis
      susceptible A/J mice. In contrast, significantly less ERK-1/2 activation is found
      in the hearts of myocarditis-resistant C57BL/6 mice. Therefore, the ERK-1/2
      response to CVB3 infection may contribute to differential host susceptibility to
      viral myocarditis.

PMID- 12070304
TI  - Regulation of seizure spreading by neuroserpin and tissue-type plasminogen
      activator is plasminogen-independent.
AB  - Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase
      expressed in the CNS during events that require neuronal plasticity. In this
      study we demonstrate that endogenous tPA mediates the progression of kainic acid
      induced (KA-induced) seizures by promoting the synchronization of neuronal
      activity required for seizure spreading, and that, unlike KA-induced cell death,
      this activity is plasminogen-independent. Specifically, seizure induction by KA
      injection into the amygdala induces tPA activity and cell death in both
      hippocampi, and unilateral treatment of rats with neuroserpin, a natural
      inhibitor of tPA in the brain, enhances neuronal survival in both hippocampi.
      Inhibition of tPA within the hippocampus by neuroserpin treatment does not
      prevent seizure onset but instead markedly delays the progression of seizure
      activity in both rats and wild-type mice. In tPA-deficient mice, seizure
      progression is significantly delayed, and neuroserpin treatment does not further
      delay seizure spreading. In contrast, plasminogen-deficient mice show a pattern
      of seizure spreading and a response to neuroserpin that is similar to that of
      wild-type animals. These findings indicate that tPA acts on a substrate other
      than plasminogen and that the effects of neuroserpin on seizure progression and
      neuronal cell survival are mediated through the inhibition of tPA.

PMID- 12070305
TI  - Myeloerythroid-restricted progenitors are sufficient to confer radioprotection
      and provide the majority of day 8 CFU-S.
AB  - Whole-body irradiation at the minimal lethal dose causes bone marrow failure and
      death within 12-18 days. To identify the principal components of the
      hematopoietic system that are radioprotective, we transplanted lethally
      irradiated mice with purified progenitors: common myeloid progenitors (CMPs),
      megakaryocyte/erythrocyte-restricted progenitors (MEPs), or granulocyte/monocyte
      restricted progenitors (GMPs). Transplanted CMPs gave rise to cells both of the
      granulocyte/monocyte (GM) series and the megakaryocyte/erythrocyte series,
      whereas GMPs or MEPs showed reconstitution of only GM or ME cells, respectively.
      CMPs and MEPs but not GMPs protected mice in a dose-dependent manner, suggesting
      that erythrocytes, platelets, or both are the critical effectors of
      radioprotection. Accordingly, CMPs and MEPs formed robust colonies in recipient
      bone marrow and spleen, whereas GMPs formed small colonies that rapidly
      disappeared. Direct comparisons of spleen CFU (CFU-S) potentials among each
      progenitor subset showed that MEPs contain the vast majority of day 8 CFU-S
      activity, suggesting that day 8 CFU-S are the precursors of radioprotective cell
      subsets. All animals radioprotected for 30 days subsequently survived for at
      least 6 months post-transplant, and showed only host-derived hematopoiesis after
      30 days. These findings suggest that rare hematopoietic stem cells survive
      myeloablation that can eventually repopulate irradiated hosts if myeloerythroid
      restricted progenitors transiently rescue ablated animals through the critical
      window of bone marrow failure.

PMID- 12070306
TI  - APRIL modulates B and T cell immunity.
AB  - The TNF-like ligands APRIL and BLyS are close relatives and share the capacity to
      bind the receptors TACI and BCMA. BLyS has been shown to play an important role
      in B cell homeostasis and autoimmunity, but the biological role of APRIL remains
      less well defined. Analysis of T cells revealed an activation-dependent increase
      in APRIL mRNA expression. We therefore generated mice expressing APRIL as a
      transgene in T cells. These mice appeared normal and showed no signs of B cell
      hyperplasia. Transgenic T cells revealed a greatly enhanced survival in vitro as
      well as enhanced survival of staphylococcal enterotoxin B-reactive CD4+ T cells
      in vivo, which both directly correlate with elevated Bcl-2 levels. Analysis of
      humoral responses to T cell-dependent antigens in the transgenic mice indicated
      that APRIL affects only IgM but not IgG responses. In contrast, T cell
      independent type 2 (TI-2) humoral response was enhanced in APRIL transgenic mice.
      As TACI was previously reported to be indispensable for TI-2 antibody formation,
      these results suggest a role for APRIL/TACI interactions in the generation of
      this response. Taken together, our data indicate that APRIL is involved in the
      induction and/or maintenance of T and B cell responses.

PMID- 12070307
TI  - Identification of a biochemical link between energy intake and energy
      expenditure.
AB  - Obesity is the result of an imbalance between energy intake and energy
      expenditure. Using high-density DNA microarrays and Northern analyses, we
      demonstrated that the activation of a nutrient-sensing pathway, the hexosamine
      biosynthesis pathway (HBP), rapidly decreased the expression of a cluster of
      nuclear-encoded mitochondrial genes involved in skeletal muscle oxidative
      phosphorylation. Conversely, the expression of uncoupling protein-1 and of the
      same mitochondrial genes was increased in brown adipose tissue. Most important,
      these transcriptional changes were accompanied by a marked decrease in whole-body
      energy expenditure. Short-term overfeeding replicated this transcriptional
      pattern, suggesting that this adaptation to nutrient abundance occurs under
      physiological conditions. Thus, the activation of the HBP by nutrients represents
      a biochemical link between nutrient availability, mitochondrial proteins, and
      energy expenditure, and it is likely to play an important role in the regulation
      of energy balance.

PMID- 12070308
TI  - Lifetime exposure to a soluble TGF-beta antagonist protects mice against
      metastasis without adverse side effects.
AB  - TGF-betas play diverse and complex roles in many biological processes. In
      tumorigenesis, they can function either as tumor suppressors or as pro-oncogenic
      factors, depending on the stage of the disease. We have developed transgenic mice
      expressing a TGF-beta antagonist of the soluble type II TGF-beta receptor:Fc
      fusion protein class, under the regulation of the mammary-selective MMTV-LTR
      promoter/enhancer. Biologically significant levels of antagonist were detectable
      in the serum and most tissues of this mouse line. The mice were resistant to the
      development of metastases at multiple organ sites when compared with wild-type
      controls, both in a tail vein metastasis assay using isogenic melanoma cells and
      in crosses with the MMTV-neu transgenic mouse model of metastatic breast cancer.
      Importantly, metastasis from endogenous mammary tumors was suppressed without any
      enhancement of primary tumorigenesis. Furthermore, aged transgenic mice did not
      exhibit the severe pathology characteristic of TGF-beta null mice, despite
      lifetime exposure to the antagonist. The data suggest that in vivo the antagonist
      may selectively neutralize the undesirable TGF-beta associated with metastasis,
      while sparing the regulatory roles of TGF-betas in normal tissues. Thus this
      soluble TGF-beta antagonist has potential for long-term clinical use in the
      prevention of metastasis.

PMID- 12070309
TI  - Biotin dependency due to a defect in biotin transport.
AB  - We describe a 3-year-old boy with biotin dependency not caused by biotinidase,
      holocarboxylase synthetase, or nutritional biotin deficiency. We sought to define
      the mechanism of his biotin dependency. The child became acutely encephalopathic
      at age 18 months. Urinary organic acids indicated deficiency of several biotin
      dependent carboxylases. Symptoms improved rapidly following biotin
      supplementation. Serum biotinidase activity and Biotinidase gene sequence were
      normal. Activities of biotin-dependent carboxylases in PBMCs and cultured skin
      fibroblasts were normal, excluding biotin holocarboxylase synthetase deficiency.
      Despite extracellular biotin sufficiency, biotin withdrawal caused recurrent
      abnormal organic aciduria, indicating intracellular biotin deficiency. Biotin
      uptake rates into fresh PBMCs from the child and into his PBMCs transformed with
      Epstein Barr virus were about 10% of normal fresh and transformed control cells,
      respectively. For fresh and transformed PBMCs from his parents, biotin uptake
      rates were consistent with heterozygosity for an autosomal recessive genetic
      defect. Increased biotin breakdown was ruled out, as were artifacts of biotin
      supplementation and generalized defects in membrane permeability for biotin.
      These results provide evidence for a novel genetic defect in biotin transport.
      This child is the first known with this defect, which should now be included in
      the identified causes of biotin dependency.

PMID- 12070310
TI  - Estrogen alters thresholds for B cell apoptosis and activation.
AB  - Estrogen is thought to contribute to the increased frequency of autoimmune
      disorders occurring in females, but a molecular basis for its effects on
      autoimmunity remains to be elucidated. We have shown previously that estrogen
      leads to the survival and activation of autoreactive cells in the naive
      repertoire. To identify the molecular pathways involved in B cell tolerance, we
      sought to identify genes that are differentially regulated by estrogen in mouse B
      cells. Several genes involved in B cell activation and survival, including cd22,
      shp-1, bcl-2, and vcam-1, were upregulated by estrogen in B cells. We found that
      overexpression of CD22 and SHP-1 in B cells decreased B cell receptor signaling.
      Estrogen receptors alpha and beta are expressed on B cells and are functional,
      since they can directly upregulate expression of CD22, SHP-1, and Bcl-2. Estrogen
      treatment protected isolated primary B cells from B cell receptor-mediated
      apoptosis. These results suggest that estrogen induces a genetic program that
      alters survival and activation of B cells in a B cell-autonomous fashion and thus
      skews the naive immune system toward autoreactivity.

PMID- 12070311
TI  - Novel synthetic amino acid copolymers that inhibit autoantigen-specific T cell
      responses and suppress experimental autoimmune encephalomyelitis.
AB  - Copolymer 1 (Cop 1, Copaxone [Teva Marion Partners, Kansas City, Missouri, USA]),
      a random amino acid copolymer of tyrosine (Y), glutamic acid (E), alanine (A),
      and lysine (K), reduces the frequency of relapses by 30% in relapsing-remitting
      multiple sclerosis (MS) patients. In the present study, novel random four-amino
      acid copolymers, whose design was based on the nature of the anchor residues of
      the immunodominant epitope of myelin basic protein (MBP) 85-99 and of the binding
      pockets of MS-associated HLA-DR2 (DRB1*1501), have been synthesized by solid
      phase chemistry. Poly (Y, F, A, K) (YFAK) inhibited binding of the biotinylated
      MBP 86-100 epitope to HLA-DR2 molecules more efficiently than did either
      unlabeled MBP 85-99 or any other copolymer including Cop 1. Moreover, YFAK and
      poly (F, A, K) (FAK) were much more effective than Cop 1 in inhibition of MBP 85
      99-specific HLA-DR2-restricted T cell clones. Most importantly, these novel
      copolymers suppressed experimental autoimmune encephalomyelitis, induced in the
      susceptible SJL/J (H-2(s)) strain of mice with the encephalitogenic epitope PLP
      139-151, more efficiently than did Cop 1. Thus, random synthetic copolymers
      designed according to the binding motif of the human immunodominant epitope MBP
      85-99 and the binding pockets of HLA-DR2 might be more beneficial than Cop 1 in
      treatment of MS.

PMID- 12070312
TI  - Chemical-modification rescue assessed by mass spectrometry demonstrates that
      gamma-thia-lysine yields the same activity as lysine in aldolase.
AB  - The role of active site residues in fructose 1,6-bisphosphate aldolase is
      investigated by chemical-modification rescue. An active-site mutation, K107C, is
      constructed in a background where the four solvent-accessible cysteine residues
      are converted to alanine. The resulting mutant, tetK107C, when reacted with
      bromoethylamine (BrEA), shows a 40-fold increase in activity (to 80% that of wild
      type). Determination of the sites and their degree of modification using
      electrospray ionization Fourier transform mass spectrometry (ESI-FTMS) is
      developed, allowing correlation of activity after chemical modification rescue to
      the degree of modification. The stoichiometry of the reaction is 2.5
      aminoethylations per subunit, as measured by ESI-FTMS. Protein modification with
      a double-labeled mix (1:1) of natural abundance isotope (d(0)-BrEA) and 2
      bromoethyl-1,1,2,2-d4-amine hydrobromide (d(4)-BrEA), followed by dialysis and
      trypsin digestion, shows aminoethylated peptides as "twin peptides" separated by
      four mass units in ESI-FTMS analysis. Using this detection procedure under
      nondenaturing (native) conditions, C107 is aminoethylated, whereas the four
      buried thiols remain unlabeled. Aminoethylation of other residues is observed,
      and correlates with those peptides containing histidine, methionine, and/or the
      amino terminus. Quantification of the aminoethylation reaction is achieved by
      labeling with nondeuterated d(0)-BrEA under denaturing conditions following
      double labeling under native conditions. In addition to complete labeling all
      five thiols, the intensity of the d(0)-BrEA peak for C107 containing peptides
      increases, and the change in the d(0)/d(4) ratio between native and denaturing
      conditions shows 82 +/- 4.5% aminoethylation at C107. This correlation of
      modification with the recovered activity, indicates that gamma-thia-lysine
      replaces lysine in the catalytic mechanism. Kinetic constants measured for the
      rescued K107C mutant enzyme with the substrates fructose 1-phosphate and fructose
      1,6-bisphosphate are consistent with the role of the positively charged lysine
      binding to the C6-phosphate. ESI-FTMS, combined with this double-labeling
      procedure, allows precise identification of sites and measurement of degree of
      protein modification.

PMID- 12070313
TI  - Description of the topographical changes associated to the different stages of
      the DsbA catalytic cycle.
AB  - This paper provides a description of the surface topography of DsbA, the
      bacterial disulfide-bond forming enzyme, in the different phases of its catalytic
      cycle. Three representative states, that is, oxidized and reduced protein and a
      covalent complex mimicking the DsbA-substrate disulfide intermediate, have been
      investigated by a combination of limited proteolysis experiments and mass
      spectrometry methodologies. Protease-accessible sites are largely distributed in
      the oxidized form with a small predominance inside the thioredoxin domain.
      Proteolysis occurs even in secondary structure elements, revealing a significant
      mobility of the protein. Many cleavage sites disappear in the reduced form and
      most of the remaining ones appear with strongly reduced kinetics. The protein
      within the complex shows an intermediate behavior. This variation of flexibility
      in DsbA is probably the determining factor for the course of its catalytic cycle.
      In particular, the great mobility of the oxidized protein might facilitate the
      accommodation of its various substrates, whereas the increasing rigidity from the
      complexed to the reduced form could help the release of oxidized products. The
      formation of the complex between PID peptide and DsbA does not significantly
      protect the enzyme against proteolysis, reinforcing the results previously
      obtained by calorimetry concerning the weakness of their interaction. The few
      cleavage sites observed, however, are in favor of the presence of the peptide in
      the binding site postulated from crystallographic studies. As for the peptide
      itself, the proteolytic pattern and the protection effect exerted by DsbA could
      be explained by a preferential orientation within the binding site.

PMID- 12070314
TI  - Ca(2+) and membrane binding to annexin 3 modulate the structure and dynamics of
      its N terminus and domain III.
AB  - Annexin 3 (ANX A3) represents approximately 1% of the total protein of human
      neutrophils and promotes tight contact between membranes of isolated specific
      granules in vitro leading to their aggregation. Like for other annexins, the
      primary molecular events of the action of this protein is likely its binding to
      negatively charged phospholipid membranes in a Ca(2+)-dependent manner, via
      Ca(2+)-binding sites located on the convex side of the highly conserved core of
      the molecule. The conformation and dynamics of domain III can be affected by this
      process, as it was shown for other members of the family. The 20 amino-acid, N
      terminal segment of the protein also could be affected and also might play a role
      in the modulation of its binding to the membranes. The structure and dynamics of
      these two regions were investigated by fluorescence of the two tryptophan
      residues of the protein (respectively, W190 in domain III and W5 in the N
      terminal segment) in the wild type and in single-tryptophan mutants. By contrast
      to ANX A5, which shows a closed conformation and a buried W187 residue in the
      absence of Ca(2+), domain III of ANX A3 exhibits an open conformation and a
      widely solvent-accessible W190 residue in the same conditions. This is in
      agreement with the three-dimensional structure of the ANX A3-E231A mutant lacking
      the bidentate Ca(2+) ligand in domain III. Ca(2+) in the millimolar concentration
      range provokes nevertheless a large mobility increase of the W190 residue, while
      interaction with the membranes reduces it slightly. In the N-terminal region, the
      W5 residue, inserted in the central pore of the protein, is weakly accessible to
      the solvent and less mobile than W190. Its amplitude of rotation increases upon
      binding of Ca(2+) and returns to its original value when interacting with
      membranes. Ca(2+) concentration for half binding of the W5A mutant to negatively
      charged membranes is approximately 0.5 mM while it increases to approximately 1
      mM for the ANX A3 wild type and to approximately 3 mM for the W190 ANX A3 mutant.
      In addition to the expected perturbation of the W190 environment at the contact
      surface between the protein and the membrane bilayer, binding of the protein to
      Ca(2+) and to membranes modulates the flexibility of the ANX A3 hinge region at
      the opposite of this interface and might affect its membrane permeabilizing
      properties.

PMID- 12070315
TI  - Crystal structures of free, IMP-, and GMP-bound Escherichia coli hypoxanthine
      phosphoribosyltransferase.
AB  - Crystal structures have been determined for free Escherichia coli hypoxanthine
      phosphoribosyltransferase (HPRT) (2.9 A resolution) and for the enzyme in complex
      with the reaction products, inosine 5'-monophosphate (IMP) and guanosine 5'
      monophosphate (GMP) (2.8 A resolution). Of the known 6-oxopurine
      phosphoribosyltransferase (PRTase) structures, E. coli HPRT is most similar in
      structure to that of Tritrichomonas foetus HGXPRT, with a rmsd for 150 Calpha
      atoms of 1.0 A. Comparison of the free and product bound structures shows that
      the side chain of Phe156 and the polypeptide backbone in this vicinity move to
      bind IMP or GMP. A nonproline cis peptide bond, also found in some other 6
      oxopurine PRTases, is observed between Leu46 and Arg47 in both the free and
      complexed structures. For catalysis to occur, the 6-oxopurine PRTases have a
      requirement for divalent metal ion, usually Mg(2+) in vivo. In the free
      structure, a Mg(2+) is coordinated to the side chains of Glu103 and Asp104. This
      interaction may be important for stabilization of the enzyme before catalysis. E.
      coli HPRT is unique among the known 6-oxopurine PRTases in that it exhibits a
      marked preference for hypoxanthine as substrate over both xanthine and guanine.
      The structures suggest that its substrate specificity is due to the modes of
      binding of the bases. In E. coli HPRT, the carbonyl oxygen of Asp163 would likely
      form a hydrogen bond with the 2-exocyclic nitrogen of guanine (in the HPRT
      guanine-PRib-PP-Mg(2+) complex). However, hypoxanthine does not have a 2
      exocyclic atom and the HPRT-IMP structure suggests that hypoxanthine is likely to
      occupy a different position in the purine-binding pocket.

PMID- 12070316
TI  - Charge states rather than propensity for beta-structure determine enhanced
      fibrillogenesis in wild-type Alzheimer's beta-amyloid peptide compared to E22Q
      Dutch mutant.
AB  - The activity of the Alzheimer's amyloid beta-peptide is a sensitive function of
      the peptide's sequence. Increased fibril elongation rate of the E22Q Dutch mutant
      of the Alzheimer's amyloid beta-peptide relative to that of the wild-type peptide
      has been observed. The increased activity has been attributed to a larger
      propensity for the formation of beta structure in the monomeric E22Q mutant
      peptide in solution relative to the WT peptide. That hypothesis is tested using
      four nanosecond timescale simulations of the WT and Dutch mutant forms of the
      Abeta(10-35)-peptide in aqueous solution. The simulation results indicate that
      the propensity for formation of beta-structure is no greater in the E22Q mutant
      peptide than in the WT peptide. A significant measure of "flickering" of helical
      structure in the central hydrophobic cluster region of both the WT and mutant
      peptides is observed. The simulation results argue against the hypothesis that
      the Dutch mutation leads to a higher probability of formation of beta-structure
      in the monomeric peptide in aqueous solution. We propose that the greater
      stability of the solvated WT peptide relative to the E22Q mutant peptide leads to
      decreased fibril elongation rate in the former. Stability difference is due to
      the differing charge state of the two peptides. The other proposal leads to the
      prediction that the fibril elongation rates for the WT and the mutant E22Q should
      be similar under acid conditions.

PMID- 12070317
TI  - Nucleotide affinity for a stable phosphorylated intermediate of nucleoside
      diphosphate kinase.
AB  - Nucleoside diphosphate (NDP) kinase is transiently phosphorylated on a histidine
      of the active site during the catalytic cycle. In the presence of a nucleotide
      acceptor, the phosphohistidine bond is unstable and the phosphate is transferred
      to the acceptor in less than 1 msec. We describe the synthesis of an analog of
      the phosphoenzyme intermediate with an inactive mutant of NDP kinase in which the
      catalytic histidine is replaced by a cysteine. In two sequential disulfide
      exchange reactions, a thiophosphate group reacts with the thiol function of the
      cysteine that had previously reacted with dithionitrobenzoate (DTNB). The
      thiophosphoenzyme presents a 400,000-fold increased stability in the presence of
      NDPs compared with the phosphoenzyme. The binding of NDP is studied at the steady
      state and presteady state. Data were analyzed according to a bimolecular
      association model. For the first time, the true equilibrium dissociation
      constants of NDP for the analog of the phosphoenzyme are determined in the
      absence of phosphotransfer, allowing a better understanding of the catalytic
      mechanism of the enzyme.

PMID- 12070318
TI  - The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse.
AB  - ADP-ribosyltransferases including toxins secreted by Vibrio cholera, Pseudomonas
      aerurginosa, and other pathogenic bacteria inactivate the function of human
      target proteins by attaching ADP-ribose onto a critical amino acid residue. Cross
      species polymerase chain reaction (PCR) and database mining identified the
      orthologs of these ADP-ribosylating toxins in humans and the mouse. The human
      genome contains four functional toxin-related ADP-ribosyltransferase genes (ARTs)
      and two related intron-containing pseudogenes; the mouse has six functional
      orthologs. The human and mouse ART genes map to chromosomal regions with
      conserved linkage synteny. The individual ART genes reveal highly restricted
      expression patterns, which are largely conserved in humans and the mouse. We
      confirmed the predicted extracellular location of the ART proteins by expressing
      recombinant ARTs in insect cells. Two human and four mouse ARTs contain the
      active site motif (R-S-EXE) typical of arginine-specific ADP-ribosyltransferases
      and exhibit the predicted enzyme activities. Two other human ARTs and their
      murine orthologues deviate in the active site motif and lack detectable enzyme
      activity. Conceivably, these ARTs may have acquired a new specificity or
      function. The position-sensitive iterative database search program PSI-BLAST
      connected the mammalian ARTs with most known bacterial ADP-ribosylating toxins.
      In contrast, no related open reading frames occur in the four completed genomes
      of lower eucaryotes (yeast, worm, fly, and mustard weed). Interestingly, these
      organisms also lack genes for ADP-ribosylhydrolases, the enzymes that reverse
      protein ADP-ribosylation. This suggests that the two enzyme families that
      catalyze reversible mono-ADP-ribosylation either were lost from the genomes of
      these nonchordata eucaryotes or were subject to horizontal gene transfer between
      kingdoms.

PMID- 12070319
TI  - Equilibrium denaturation studies of the Escherichia coli factor for inversion
      stimulation: implications for in vivo function.
AB  - The Factor for Inversion Stimulation (FIS) is a dimeric DNA binding protein found
      in enteric bacteria that is involved in various cellular processes, including
      stimulation of certain specialized DNA recombination events and transcription
      regulation of a large number of genes. The intracellular FIS concentration, when
      cells are grown in rich media, varies dramatically during the early logarithmic
      growth phase. Its broad range of concentrations could potentially affect the
      nature of its quaternary structure, which in turn, could affect its ability to
      function in vivo. Thus, we examined the stability of FIS homodimers under a wide
      range of concentrations relevant to in vivo expression levels. Its urea-induced
      equilibrium denaturation was monitored by far- and near-UV circular dichroism
      (CD), tyrosine fluorescence, and tyrosine fluorescence anisotropy. The
      denaturation transitions obtained were concentration-dependent and showed similar
      midpoints (C(m)) and m values, suggesting a two-state denaturation process
      involving the native dimer and unfolded monomers (N(2) <--> 2U). The
      DeltaG(H(2)O) for the unfolding of FIS determined from global and individual
      curve fitting was 14.2 kcal/mole. At concentrations <9 microM, the FIS dimer
      began to dissociate, as noted by the change in CD signal and size-exclusion high
      pressure liquid chromatography retention times and peak width. The estimated
      dimer dissociation constant based on the CD and size-exclusion chromatography
      data is in the micromolar range, resulting in a DeltaG(H(2)O) of at least 5
      kcal/mole less than that calculated from the urea denaturation data. This
      discrepancy suggests a deviation from a two-state denaturation model, perhaps due
      to a marginally stable monomeric intermediate. These observations have
      implications for the stability and function of FIS in vivo.

PMID- 12070320
TI  - Modeling of denatured state for calculation of the electrostatic contribution to
      protein stability.
AB  - Existing models of the denatured state of proteins consider only one possible
      spatial distribution of protein charges and therefore are applicable to a limited
      number of cases. In this article, a more general framework for the modeling of
      the denatured state is proposed. It is based on the assumption that the
      titratable groups of an unfolded protein can adopt a quasi-random distribution
      restricted by the protein sequence. The model was applied for the calculations of
      electrostatic interactions in two proteins, barnase and N-terminal domain of the
      ribosomal protein L9. The calculated free energy of denaturation, DeltaG(pH),
      reproduces the experimental data better than the commonly used null approximation
      (NA). It was shown that the seemingly good agreement with experimental data
      obtained by NA originates from the compensatory effect between the pairwise
      electrostatic interactions and the desolvation energy of the individual sites. It
      was also found that the ionization properties of denatured proteins are
      influenced by the protein sequence.

PMID- 12070321
TI  - Factors contributing to decreased protein stability when aspartic acid residues
      are in beta-sheet regions.
AB  - Asp residues are significantly under represented in beta-sheet regions of
      proteins, especially in the middle of beta-strands, as found by a number of
      studies using statistical, modeling, or experimental methods. To further
      understand the reasons for this under representation of Asp, we prepared and
      analyzed mutants of a beta-domain. Two Gln residues of the immunoglobulin light
      chain variable domain (V(L)) of protein Len were replaced with Asp, and then the
      effects of these changes on protein stability and protein structure were studied.
      The replacement of Q38D, located at the end of a beta-strand, and that of Q89D,
      located in the middle of a beta-strand, reduced the stability of the parent
      immunoglobulin V(L) domain by 2.0 kcal/mol and 5.3 kcal/mol, respectively.
      Because the Q89D mutant of the wild-type V(L)-Len domain was too unstable to be
      expressed as a soluble protein, we prepared the Q89D mutant in a triple mutant
      background, V(L)-Len M4L/Y27dD/T94H, which was 4.2 kcal/mol more stable than the
      wild-type V(L)-Len domain. The structures of mutants V(L)-Len Q38D and V(L)-Len
      Q89D/M4L/Y27dD/T94H were determined by X-ray diffraction at 1.6 A resolution. We
      found no major perturbances in the structures of these Q-->D mutant proteins
      relative to structures of the parent proteins. The observed stability changes
      have to be accounted for by cumulative effects of the following several factors:
      (1) by changes in main-chain dihedral angles and in side-chain rotomers, (2) by
      close contacts between some atoms, and, most significantly, (3) by the
      unfavorable electrostatic interactions between the Asp side chain and the
      carbonyls of the main chain. We show that the Asn side chain, which is of similar
      size but neutral, is less destabilizing. The detrimental effect of Asp within a
      beta-sheet of an immunoglobulin-type domain can have very serious consequences. A
      somatic mutation of a beta-strand residue to Asp could prevent the expression of
      the domain both in vitro and in vivo, or it could contribute to the pathogenic
      potential of the protein in vivo.

PMID- 12070322
TI  - The dual role of a loop with low loop contact distance in folding and domain
      swapping.
AB  - Alpha helices, beta strands, and loops are the basic building blocks of protein
      structure. The folding kinetics of alpha helices and beta strands have been
      investigated extensively. However, little is known about the formation of loops.
      Experimental studies show that for some proteins, the formation of a single loop
      is the rate-determining step for folding, whereas for others, a loop (or turn)
      can misfold to serve as the hinge loop region for domain-swapped species.
      Computer simulations of an all-atom model of fragment B of Staphylococcal protein
      A found that the formation of a single loop initiates the dominant folding
      pathway. On the other hand, the stability analysis of intermediates suggests that
      the same loop is a likely candidate to serve as a hinge loop for domain swapping.
      To interpret the simulation result, we developed a simple structural parameter:
      the loop contact distance (LCD), or the sequence distance of contacting residues
      between a loop and the rest of the protein. The parameter is applied to a number
      of other proteins, including SH3 domains and prion protein. The results suggest
      that a locally interacting loop (low LCD) can either promote folding or serve as
      the hinge region for domain swapping. Thus, there is an intimate connection
      between folding and domain swapping, a possible cause of misfolding and
      aggregation.

PMID- 12070324
TI  - High-throughput screening of soluble recombinant proteins.
AB  - The aims of high-throughput (HTP) protein production systems are to obtain well
      expressed and highly soluble proteins, which are preferred candidates for use in
      structure-function studies. Here, we describe the development of an efficient and
      inexpensive method for parallel cloning, induction, and cell lysis to produce
      multiple fusion proteins in Escherichia coli using a 96-well format. Molecular
      cloning procedures, used in this HTP system, require no restriction digestion of
      the PCR products. All target genes can be directionally cloned into eight
      different fusion protein expression vectors using two universal restriction sites
      and with high efficiency (>95%). To screen for well-expressed soluble fusion
      protein, total cell lysates of bacteria culture ( approximately 1.5 mL) were
      subjected to high-speed centrifugation in a 96-tube format and analyzed by
      multiwell denaturing SDS-PAGE. Our results thus far show that 80% of the genes
      screened show high levels of expression of soluble products in at least one of
      the eight fusion protein constructs. The method is well suited for automation and
      is applicable for the production of large numbers of proteins for genome-wide
      analysis.

PMID- 12070323
TI  - In search for more accurate alignments in the twilight zone.
AB  - A major bottleneck in comparative modeling is the alignment quality; this is
      especially true for proteins whose distant relationships could be reliably
      recognized only by recent advances in fold recognition. The best algorithms excel
      in recognizing distant homologs but often produce incorrect alignments for over
      50% of protein pairs in large fold-prediction benchmarks. The alignments obtained
      by sequence-sequence or sequence-structure matching algorithms differ
      significantly from the structural alignments. To study this problem, we developed
      a simplified method to explicitly enumerate all possible alignments for a pair of
      proteins. This allowed us to estimate the number of significantly different
      alignments for a given scoring method that score better than the structural
      alignment. Using several examples of distantly related proteins, we show that for
      standard sequence-sequence alignment methods, the number of significantly
      different alignments is usually large, often about 10(10) alternatives. This
      distance decreases when the alignment method is improved, but the number is still
      too large for the brute force enumeration approach. More effective strategies
      were needed, so we evaluated and compared two well-known approaches for searching
      the space of suboptimal alignments. We combined their best features and produced
      a hybrid method, which yielded alignments that surpassed the original alignments
      for about 50% of protein pairs with minimal computational effort.

PMID- 12070325
TI  - Alpha-crystallin binds to the aggregation-prone molten-globule state of alkaline
      protease: implications for preventing irreversible thermal denaturation.
AB  - Alpha-crystallin, the major eye-lens protein with sequence homology with heat
      shock proteins (HSPs), acts like a molecular chaperone by suppressing the
      aggregation of damaged crystallins and proteins. To gain more insight into its
      chaperoning ability, we used a protease as the model system that is known to
      require a propeptide (intramolecular chaperone) for its proper folding. The
      protease ("N" state) from Conidiobolus macrosporus (NCIM 1298) unfolds at pH 2.0
      ("U" state) through a partially unfolded "I" state at pH 3.5 that undergoes
      transition to a molten globule-(MG) like "I(A)" state in the presence of 0.5 M
      sodium sulfate. The thermally-stressed I(A) state showed complete loss of
      structure and was prone to aggregation. Alpha-crystallin was able to bind to this
      state and suppress its aggregation, thereby preventing irreversible denaturation
      of the enzyme. The alpha-crystallin-bound I(A) state exhibited native-like
      secondary and tertiary structure showing the interaction of alpha-crystallin with
      the MG state of the protease. 8-Anilinonaphthalene sulphonate (ANS) binding
      studies revealed the involvement of hydrophobic interactions in the formation of
      the complex of alpha-crystallin and protease. Refolding of acid-denatured
      protease by dilution to pH 7.5 resulted in aggregation of the protein. Unfolding
      of the protease in the presence of alpha-crystallin and its subsequent refolding
      resulted in the generation of a near-native intermediate with partial secondary
      and tertiary structure. Our studies represent the first report of involvement of
      a molecular chaperone-like alpha-crystallin in the unfolding and refolding of a
      protease. Alpha-crystallin blocks the unfavorable pathways that lead to
      irreversible denaturation of the alkaline protease and keeps it in a near-native,
      folding-competent intermediate state.

PMID- 12070326
TI  - Efficient docking of peptides to proteins without prior knowledge of the binding
      site.
AB  - Reliability in docking of ligand molecules to proteins or other targets is an
      important challenge for molecular modeling. Applications of the docking technique
      include not only prediction of the binding mode of novel drugs, but also other
      problems like the study of protein-protein interactions. Here we present a study
      on the reliability of the results obtained with the popular AutoDock program. We
      have performed systematical studies to test the ability of AutoDock to reproduce
      eight different protein/ligand complexes for which the structure was known,
      without prior knowledge of the binding site. More specifically, we look at
      factors influencing the accuracy of the final structure, such as the number of
      torsional degrees of freedom in the ligand. We conclude that the Autodock program
      package is able to select the correct complexes based on the energy without prior
      knowledge of the binding site. We named this application blind docking, as the
      docking algorithm is not able to "see" the binding site but can still find it.
      The success of blind docking represents an important finding in the era of
      structural genomics.

PMID- 12070327
TI  - Probing metal ion binding and conformational properties of the colicin E9
      endonuclease by electrospray ionization time-of-flight mass spectrometry.
AB  - Nano-electrospray ionization time-of-flight mass spectrometry (ESI-MS) was used
      to study the conformational consequences of metal ion binding to the colicin E9
      endonuclease (E9 DNase) by taking advantage of the unique capability of ESI-MS to
      allow simultaneous assessment of conformational heterogeneity and metal ion
      binding. Alterations of charge state distributions on metal ion binding/release
      were correlated with spectral changes observed in far- and near-UV circular
      dichroism (CD) and intrinsic tryptophan fluorescence. In addition,
      hydrogen/deuterium (H/D) exchange experiments were used to probe structural
      integrity. The present study shows that ESI-MS is sensitive to changes of the
      thermodynamic stability of E9 DNase as a result of metal ion binding/release in a
      manner consistent with that deduced from proteolysis and calorimetric
      experiments. Interestingly, acid-induced release of the metal ion from the E9
      DNase causes dramatic conformational instability associated with a loss of fixed
      tertiary structure, but secondary structure is retained. Furthermore, ESI-MS
      enabled the direct observation of the noncovalent protein complex of E9 DNase
      bound to its cognate immunity protein Im9 in the presence and absence of Zn(2+).
      Gas-phase dissociation experiments of the deuterium-labeled binary and ternary
      complexes revealed that metal ion binding, not Im9, results in a dramatic
      exchange protection of E9 DNase in the complex. In addition, our metal ion
      binding studies and gas-phase dissociation experiments of the ternary E9 DNase
      Zn(2+)-Im9 complex have provided further evidence that electrostatic interactions
      govern the gas phase ion stability.

PMID- 12070329
TI  - Sulfate anion stabilization of native ribonuclease A both by anion binding and by
      the Hofmeister effect.
AB  - Data are reported for T(m), the temperature midpoint of the thermal unfolding
      curve, of ribonuclease A, versus pH (range 2-9) and salt concentration (range 0-1
      M) for two salts, Na(2)SO(4) and NaCl. The results show stabilization by sulfate
      via anion-specific binding in the concentration range 0-0.1 M and via the
      Hofmeister effect in the concentration range 0.1-1.0 M. The increase in T(m)
      caused by anion binding at 0.1 M sulfate is 20 degrees at pH 2 but only 1 degree
      at pH 9, where the net proton charge on the protein is near 0. The 10 degrees
      increase in T(m) between 0.1 and 1.0 M Na(2)SO(4), caused by the Hofmeister
      effect, is independent of pH. A striking property of the NaCl results is the
      absence of any significant stabilization by 0.1 M NaCl, which indicates that any
      Debye screening is small. pH-dependent stabilization is produced by 1 M NaCl: the
      increase in T(m) between 0 and 1.0 M is 14 degrees at pH 2 but only 1 degree at
      pH 9. The 14 degree increase at pH 2 may result from anion binding or from both
      binding and Debye screening. Taken together, the results for Na(2)SO(4) and NaCl
      show that native ribonuclease A is stabilized at low pH in the same manner as
      molten globule forms of cytochrome c and apomyoglobin, which are stabilized at
      low pH by low concentrations of sulfate but only by high concentrations of
      chloride.

PMID- 12070328
TI  - Comparison of protein fragments identified by limited proteolysis and by
      computational cutting of proteins.
AB  - Here we present a comparison between protein fragments produced by limited
      proteolysis and those identified by computational cutting based on the building
      block folding model. The principles upon which the two methods are based are
      different. Limited proteolysis of natively folded proteins occurs at flexible
      sites and never at the level of chain segments of regular secondary structure
      such as alpha-helices. Therefore, the targets for limited proteolysis are locally
      unfolded regions. In contrast, the computational cutting algorithm considers the
      compactness of the fragments, their nonpolar buried surface area, and their
      isolatedness, that is, the surface area which was buried prior to the cutting and
      becomes exposed subsequently. Despite the different criteria, there is an overall
      correspondence between sites or regions of limited proteolysis with those
      identified by computational cutting. The computational cutting method has been
      applied to several model proteins for which detailed limited proteolysis data are
      available, namely apomyoglobin, cytochrome c, ribonuclease A, alpha-lactalbumin,
      and thermolysin. As expected, more cuts are obtained computationally than
      experimentally and the agreement is better when a number of proteolytic enzymes
      are used. For example, cytochrome c is cleaved by thermolysin at 56-57, 45-46,
      and at 80-81, and by proteinase K at 48-49 and 50-51. Incubation of the
      noncovalent and native-like complex of cytochrome c fragments 1-56 and 57-104
      with proteinase K yielded the gapped protein species 1-48/57-104 and finally 1
      40/57-104. Computational cutting of cytochrome c reproduced the major
      experimental observations, with cuts at 47, 64-65 or 65-66 and 80-81 and an
      unstable 32-47 region not assigned to any building block. The next step, not
      addressed in this work, is to probe the ability of the generated fragments to
      fold independently. Since both the computational algorithm and limited
      proteolysis attempt to dissect the protein folding problem, the general agreement
      between the two procedures is gratifying. This consistency allows us to propose
      the use of limited proteolysis to produce protein fragments that can adopt an
      independent folding and, therefore, to study folding intermediates. The results
      of the present study appear to validate the building block folding model and are
      in line with the proposal that protein folding is a hierarchical process, where
      parts constituting local minima of energy fold first, with their subsequent
      association and mutual stabilization to finally yield the global fold.

PMID- 12070330
TI  - Structural basis for cyclodextrins' suppression of human growth hormone
      aggregation.
AB  - Many therapeutic proteins require storage at room temperature for extended
      periods of time. This can lead to aggregation and loss of function. Cyclodextrins
      (CDs) have been shown to function as aggregation suppressors for a wide range of
      proteins. Their potency is often ascribed to their affinity for aromatic amino
      acids, whose surface exposure would otherwise lead to protein association.
      However, no detailed structural studies are available. Here we investigate the
      interactions between human growth hormone (hGH) and different CDs at low pH.
      Although hGH aggregates readily at pH 2.5 in 1 M NaCl to form amorphous
      aggregates, the presence of 25 to 50 mM of various beta-CD derivatives is
      sufficient to completely avoid this. alpha- and gamma-CD are considerably less
      effective. Stopped-flow data on the aggregation reaction in the presence of beta
      CD are analyzed according to a minimalist association model to yield an apparent
      hGH-beta-CD dissociation constant of approximately 6 mM. This value is very
      similar to that obtained by simple fluorescence-based titration of hGH with beta
      CD. Nuclear magnetic resonance studies indicate that beta-CD leads to a more
      unfolded conformation of hGH at low pH and predominantly binds to the aromatic
      side-chains. This indicates that aromatic amino acids are important components of
      regions of residual structure that may form nuclei for aggregation.

PMID- 12070331
TI  - Characterization of Ejl, the cell-wall amidase coded by the pneumococcal
      bacteriophage Ej-1.
AB  - The Ejl amidase is coded by Ej-1, a temperate phage isolated from the atypical
      pneumococcus strain 101/87. Like all the pneumococcal cell-wall lysins, Ejl has a
      bimodular organization; the catalytic region is located in the N-terminal module,
      and the C-terminal module attaches the enzyme to the choline residues of the
      pneumococcal cell wall. The structural features of the Ejl amidase, its
      interaction with choline, and the structural changes accompanying the ligand
      binding have been characterized by CD and IR spectroscopies, differential
      scanning calorimetry, analytical ultracentrifugation, and FPLC. According to
      prediction and spectroscopic (CD and IR) results, Ejl would be composed of short
      beta-strands (ca. 36%) connected by long loops (ca. 17%), presenting only two
      well-predicted alpha-helices (ca. 12%) in the catalytic module. Its polypeptide
      chain folds into two cooperative domains, corresponding to the N- and C-terminal
      modules, and exhibits a monomer <--> dimer self-association equilibrium. Choline
      binding induces small rearrangements in Ejl secondary structure but enhances the
      amidase self-association by preferential binding to Ejl dimers and tetramers.
      Comparison of LytA, the major pneumococcal amidase, with Ejl shows that the
      sequence differences (15% divergence) strongly influence the amidase stability,
      the organization of the catalytic module in cooperative domains, and the self
      association state induced by choline. Moreover, the ligand affinity for the
      choline-binding locus involved in regulation of the amidase dimerization is
      reduced by a factor of 10 in Ejl. Present results evidence that sequence
      differences resulting from the natural variability found in the cell wall
      amidases coded by pneumococcus and its bacteriophages may significantly alter the
      protein structure and its attachment to the cell wall.

PMID- 12070332
TI  - Transmembrane signal transduction of the alpha(IIb)beta(3) integrin.
AB  - Integrins are composed of noncovalently bound dimers of an alpha- and a beta
      subunit. They play an important role in cell-matrix adhesion and signal
      transduction through the cell membrane. Signal transduction can be initiated by
      the binding of intracellular proteins to the integrin. Binding leads to a major
      conformational change. The change is passed on to the extracellular domain
      through the membrane. The affinity of the extracellular domain to certain ligands
      increases; thus at least two states exist, a low-affinity and a high-affinity
      state. The conformations and conformational changes of the transmembrane (TM)
      domain are the focus of our interest. We show by a global search of helix-helix
      interactions that the TM section of the family of integrins are capable of
      adopting a structure similar to the structure of the homodimeric TM protein
      Glycophorin A. For the alpha(IIb)beta(3) integrin, this structural motif
      represents the high-affinity state. A second conformation of the TM domain of
      alpha(IIb)beta(3) is identified as the low-affinity state by known mutational and
      nuclear magnetic resonance (NMR) studies. A transition between these two states
      was determined by molecular dynamics (MD) calculations. On the basis of these
      calculations, we propose a three-state mechanism.

PMID- 12070333
TI  - Properties of Bacillus cereus hemolysin II: a heptameric transmembrane pore.
AB  - The gene encoding hemolysin II (HlyII) was amplified from Bacillus cereus genomic
      DNA and a truncated mutant, HlyII(DeltaCT), was constructed lacking the 94 amino
      acid extension at the C terminus. The proteins were produced in an E. coli cell
      free in vitro transcription and translation system, and were shown to assemble
      into SDS-stable oligomers on rabbit erythrocyte membranes and liposomes. The
      hemolytic activity of HlyII was measured with rabbit erythrocytes yielding an
      HC(50) value of 1.64 ng mL(-1), which is over 15 times more potent than
      staphylococcal alpha-hemolysin. HlyII(DeltaCT) was about eight times less potent
      than HlyII in this assay. Limited proteolysis of the oligomers formed by HlyII
      and HlyII(DeltaCT) on red cell membranes showed that the C-terminal extension is
      sensitive to digestion, while HlyII(DeltaCT) is protease resistant and migrates
      with an electrophoretic mobility similar to that of digested HlyII. HlyII forms
      moderately anion selective, rectifying pores (I(+80)/I(-80) = 0.57, 1 M KCl, pH
      7.4) in planar lipid bilayers of diphytanoylphosphatidylcholine with a unitary
      conductance of 637 pS (1 M KCl, 5 mM HEPES, pH 7.4) and exhibits no gating over a
      wide range of applied potentials (-160 to +160 mV). In addition, it was
      demonstrated that HlyII forms a homoheptameric pore by using gel shift
      electrophoresis aided by a genetically encoded oligoaspartate tag. Although they
      share limited primary sequence identity (30%), these data confirm that HlyII is a
      structural and functional homolog of staphylococcal alpha-hemolysin.

PMID- 12070334
TI  - Interactions between PEG and type I soluble tumor necrosis factor receptor:
      modulation by pH and by PEGylation at the N terminus.
AB  - The effects of polyethylene glycol (PEG) on protein structure and the molecular
      details that regulate its association to polypeptides are largely unknown. These
      issues were addressed using type I soluble tumor necrosis factor receptor (sTNF
      RI) as a model system. Changes in solution viscosity established that a truncated
      form of sTNF-RI bound free PEG in a pH-dependent manner. Above pH 5.3, the
      viscosity escalated as the pH increased, while no effect occurred below pH 5.0.
      Conjugation of 2 kD, 5 kD, or 20 kD PEG to the N terminus attenuated the
      viscosity at the higher pH values. Tryptophan phosphorescence spectroscopy
      correlated changes in the protein structure about Trp-107, at the C terminus,
      with the pH-dependent and PEGylation-dependent attenuation of the viscosity. The
      results indicate that specific interactions between PEG and the truncated form of
      sTNF-RI are elicited by an increased flexibility of the truncated protein
      combined perhaps with removal of steric or charge barriers. Covalently bound PEG
      at the N terminus reduced the protein affinity for the free polymer and induced a
      more rigid and polar configuration around Trp-107. Deprotonation of His-105,
      which is perpendicular to Trp-107, was integral to the binding mechanism
      producing a pH-dependent switching mechanism. These findings stress the
      importance of surface charge and structural plasticity in determining
      macromolecular binding affinities and demonstrate the ability of conjugated PEG
      to modify the localized surface structure in proteins away from the site of
      conjugation.

PMID- 12070335
TI  - The neuropeptide Y monomer in solution is not folded in the pancreatic
      polypeptide fold.
AB  - Fluorescence-labelled analogs of NPY, a 36-amino acid peptide amide, were
      synthesized by solid-phase peptide synthesis and used for fluorescence-resonance
      energy transfer studies to investigate the conformation. Energy-transfer
      efficiency measurements in different media at the concentration of 10 microM are
      in agreement with a model of the NPY structure proposed by NMR studies (performed
      at millimolar concentration) in which the C-terminal part of the molecule adopts
      an alpha-helical conformation while the N-terminal part is flexible. According to
      this model, the alpha-helix is stabilized by intermolecular hydrophobic
      interactions because of the formation of dimers. The decrease of the peptide
      concentration causes a shift of the dimerization equilibrium toward the monomeric
      form. Energy-transfer efficiency measurements performed at lower concentrations
      do not support the hypothesis of the folding back of the N-terminal tail onto the
      C-terminal alpha-helix to yield the so-called "PP-fold" conformation. This
      structure is observed in the crystal structure of avian pancreatic polypeptide, a
      member of the NPY peptide hormone family, and it has been considered to be the
      bioactive one. Our results complete the structural characterization of NPY in
      solution at concentration ranges in which NMR experiments are not feasible.
      Furthermore, these results open the way to study the conformation of the receptor
      bound ligand.

PMID- 12070336
TI  - Correlation of protein functional properties in the crystal and in solution: the
      case study of T-state hemoglobin.
AB  - The relevance of three-dimensional structures of proteins, determined by X-ray
      crystallography, is an important issue that is becoming even more critical in
      light of the Structural Genomics Initiative. As a case study, a detailed
      comparison of functional properties of the T quaternary states of genetically or
      chemically modified human hemoglobins (Hbs) in solution and in the crystal was
      performed. Oxygen affinities of Hbs in crystals correlate with the rate constants
      of their initial combination with carbon monoxide (CO) in solution, indicating
      that changes in ligand affinity caused by the modifications are similarly
      observed in both physical states.

PMID- 12070337
TI  - Mapping the surface of Escherichia coli peptide deformylase by NMR with organic
      solvents.
AB  - Identifying potential ligand binding sites on a protein surface is an important
      first step for targeted structure-based drug discovery. While performing control
      experiments with Escherichia coli peptide deformylase (PDF), we noted that the
      organic solvents used to solubilize some ligands perturbed many of the same
      resonances in PDF as the small molecule inhibitors. To further explore this
      observation, we recorded (15)N HSQC spectra of E. coli peptide deformylase (PDF)
      in the presence of trace quantities of several simple organic solvents (acetone,
      DMSO, ethanol, isopropanol) and identified their sites of interaction from local
      perturbation of amide chemical shifts. Analysis of the protein surface structure
      revealed that the ligand-induced shift perturbations map to the active site and
      one additional surface pocket. The correlation between sites of solvent and
      inhibitor binding highlights the utility of organic solvents to rapidly and
      effectively validate and characterize binding sites on proteins prior to
      designing a drug discovery screen. Further, the solvent-induced perturbations
      have implications for the use of organic solvents to dissolve candidate ligands
      in NMR-based screens.

PMID- 12070338
TI  - Prediction of the membrane-spanning beta-strands of the major outer membrane
      protein of Chlamydia.
AB  - There is preliminary experimental evidence indicating that the major outer
      membrane protein (MOMP) of Chlamydia is a porin. We tested this hypothesis for
      the MOMP of the mouse pneumonitis serovar of Chlamydia trachomatis using two
      secondary structure prediction methods. First, an algorithm that calculates the
      mean hydrophobicity of one side of putative beta-strands predicted the positions
      of 16 transmembrane segments, a structure common to known porins. Second, outer
      loops typical of porins were assigned using an artificial neural network trained
      to predict the topology of bacterial outer-membrane proteins with a predominance
      of beta-strands. A topology model based on these results locates the four
      variable domains (VDs) of the MOMP on the outer loops and the five constant
      domains on beta-strands and the periplasmic turns. This model is consistent with
      genetic analysis and immunological and biochemical data that indicate the VDs are
      surface exposed. Furthermore, it shows significant homology with the consensus
      porin model of the program FORESST, which contrasts a proposed secondary
      structure against a data set of 349 proteins of known structure. Analysis of the
      MOMP of other chlamydial species corroborated our predicted model.

PMID- 12070339
TI  - The fibril_one on-line database: mutations, experimental conditions, and trends
      associated with amyloid fibril formation.
AB  - The association of amyloid fibril formation with a number of important diseases,
      and the extensive study of this process in vitro, has resulted in a large
      literature containing a vast amount of information about the fibril formation
      process. This includes mutations and experimental conditions that promote or
      protect against fibril formation. A database (fibril_one) was designed to hold
      information relating to the formation of fibrils. It was populated by extensive
      searches of the literature and other databases. A powerful World Wide Web query
      interface to the database was developed, enabling a simple and effective method
      to view amyloidogenic mutations associated with specific proteins. The Web
      interface was used to identify trends in the data. This revealed that mutations
      promoting fibril formation through altered folding tend to be associated with
      destabilization of the native fold. In particular, tendencies of mutations to
      disrupt the native secondary structure and packing in the hydrophobic core were
      discovered to be significant. Query access to the database is available freely on
      the World Wide Web at
      http://www.bioinformatics.leeds.ac.uk/group/online/fibril_one.

PMID- 12070341
TI  - Inverting dynamic force microscopy: from signals to time-resolved interaction
      forces.
AB  - Transient forces between nanoscale objects on surfaces govern friction, viscous
      flow, and plastic deformation, occur during manipulation of matter, or mediate
      the local wetting behavior of thin films. To resolve transient forces on the
      (sub) microsecond time and nanometer length scale, dynamic atomic force
      microscopy (AFM) offers largely unexploited potential. Full spectral analysis of
      the AFM signal completes dynamic AFM. Inverting the signal formation process, we
      measure the time course of the force effective at the sensing tip. This approach
      yields rich insight into processes at the tip and dispenses with a priori
      assumptions about the interaction, as it relies solely on measured data. Force
      measurements on silicon under ambient conditions demonstrate the distinct
      signature of the interaction and reveal that peak forces exceeding 200 nN are
      applied to the sample in a typical imaging situation. These forces are 2 orders
      of magnitude higher than those in covalent bonds.

PMID- 12070340
TI  - Blockade of vascular endothelial growth factor receptor-3 signaling inhibits
      fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea.
AB  - Vascular endothelial growth factor receptor-3 (VEGFR-3) is a major mediator of
      lymphangiogenesis. Recently, VEGFR-3 ligands, VEGF-C, and VEGF-D were reported to
      promote tumor lymphangiogenesis and lymphatic metastasis, and these processes
      were inhibited by blocking of the VEGFR-3-signaling pathway. Here, we have
      adapted the mouse corneal angiogenesis assay to study potential lymphangiogenic
      factors and inhibitors. Immunohistochemical analysis with lymphatic endothelial
      markers showed that VEGF-C induces lymphatic as well as blood vessel growth in
      the cornea. By contrast, VEGF induced angiogenesis but not lymphangiogenesis.
      Fibroblast growth factor-2 (FGF-2) stimulated both lymphangiogenesis and
      angiogenesis. FGF-2 up-regulated VEGF-C expression in vascular endothelial and
      perivascular cells. Furthermore, administration of blocking anti-VEGFR-3
      antibodies inhibited the FGF-2-induced lymphangiogenesis. These findings show
      that VEGFR-3 can mediate lymphangiogenesis induced by other growth factors.
      Because increased expression of FGF-2 and VEGF-C has been associated with
      lymphatic metastasis, our results provide a potential strategy for the inhibition
      of lymphatic metastasis in cancer therapy.

PMID- 12070342
TI  - Liquid-liquid separation in solutions of normal and sickle cell hemoglobin.
AB  - We show that in solutions of human hemoglobin (Hb)--oxy- and deoxy-Hb A or S--of
      near-physiological pH, ionic strength, and Hb concentration, liquid-liquid phase
      separation occurs reversibly and reproducibly at temperatures between 35 and 40
      degrees C. In solutions of deoxy-HbS, we demonstrate that the dense liquid
      droplets facilitate the nucleation of HbS polymers, whose formation is the
      primary pathogenic event for sickle cell anemia. In view of recent results that
      shifts of the liquid-liquid separation phase boundary can be achieved by nontoxic
      additives at molar concentrations up to 30 times lower than the protein
      concentrations, these findings open new avenues for the inhibition of the HbS
      polymerization.

PMID- 12070343
TI  - Ebselen: a substrate for human thioredoxin reductase strongly stimulating its
      hydroperoxide reductase activity and a superfast thioredoxin oxidant.
AB  - Ebselen [2-phenyl-1,2-benzisoselenazol-3(2H)-one], a seleno-organic compound with
      glutathione peroxidase-like activity is used in clinical trials against stroke.
      Human and bovine TrxR catalyzed the reduction of ebselen to ebselen selenol by
      NADPH with an apparent K(M)-value of 2.5 microM and a kcat of 588 min(-1). The
      addition of thioredoxin (Trx) stimulated the TrxR-catalyzed reduction of ebselen
      several-fold. This result was caused by a very fast oxidation of reduced Trx by
      ebselen with a rate constant in excess of 2 x 10(7) M(-1) s(-1). This rate is
      orders of magnitude faster than the reaction of dithiol Trx with insulin
      disulfides. Ebselen competed with disulfide substrates for reduction by Trx and,
      therefore, acted as an inhibitor of protein disulfide reduction by the Trx
      system. The inherent H2O2 reductase activity of mammalian TrxR dependent on its
      active-site selenocysteine residue was stimulated 10-fold by 2 microM ebselen and
      25-fold in the additional presence of 5 microM Trx. Furthermore, the apparent
      K(M)-value of TrxR for H2O2 was lowered 25-fold to about 100 microM. Our results
      demonstrate that ebselen is a TrxR peroxidase which, in the presence of Trx,
      acted as a mimic of a peroxiredoxin. The activity with TrxR and oxidation of
      reduced Trx offer mechanistic explanations for the in vivo effects of ebselen as
      an antioxidant and anti-inflammatory agent. Our results demonstrate that the
      mechanism of action of ebselen may be predominantly via the Trx system rather
      than via glutathione.

PMID- 12070344
TI  - Microsatellite evolution inferred from human-chimpanzee genomic sequence
      alignments.
AB  - Most studies of microsatellite evolution utilize long, highly mutable loci, which
      are unrepresentative of the majority of simple repeats in the human genome. Here
      we use an unbiased sample of 2,467 microsatellite loci derived from alignments of
      5.1 Mb of genomic sequence from human and chimpanzee to investigate the mutation
      process of tandemly repetitive DNA. The results indicate that the process of
      microsatellite evolution is highly heterogeneous, exhibiting differences between
      loci of different lengths and motif sizes and between species. We find a highly
      significant tendency for human dinucleotide repeats to be longer than their
      orthologues in chimpanzees, whereas the opposite trend is observed in
      mononucleotide repeat arrays. Furthermore, the rate of divergence between
      orthologues is significantly higher at longer loci, which also show significantly
      greater mutability per repeat number. These observations have important
      consequences for understanding the molecular mechanisms of microsatellite
      mutation and for the development of improved measures of genetic distance.

PMID- 12070345
TI  - Time-critical integration of formants for perception of communication calls in
      mice.
AB  - Brain mechanisms in humans group together acoustical frequency components both in
      the spectral and temporal domain, which leads to the perception of auditory
      objects and of streams of sound events that are of biological and communicative
      significance. At the perceptual level, behavioral data on mammals that clearly
      support the presence of common concepts for processing species-specific
      communication sounds are unavailable. Here, we synthesize 17 models of mouse pup
      wriggling calls, present them in sequences of four calls to the pups' mothers in
      a natural communication situation, and record the maternal response behavior. We
      show that the biological significance of a call sequence depends on grouping
      together three predominant frequency components (formants) to an acoustic object
      within a critical time window of about 30-ms lead or lag time of the first
      formant. Longer lead or lag times significantly reduce the maternal
      responsiveness. Central inhibition seems to be responsible for setting this time
      window, which is also found in numerous perceptual studies in humans. Further, a
      minimum of 100-ms simultaneous presence of the three formants is necessary for
      occurrence of response behavior. As in humans, onset-time asynchronies of
      formants and formant durations interact nonlinearly to influence the adequate
      perception of a stream of sounds. Together, these data point to common rules for
      time-critical spectral integration, perception of acoustical objects, and
      auditory streaming (perception of an acoustical Gestalt) in mice and humans.

PMID- 12070346
TI  - Contactless experiments on individual DNA molecules show no evidence for
      molecular wire behavior.
AB  - A fundamental requirement for a molecule to be considered a molecular wire (MW)
      is the ability to transport electrical charge with a reasonably low resistance.
      We have carried out two experiments that measure first, the charge transfer from
      an electrode to the molecule, and second, the dielectric response of the MW. The
      latter experiment requires no contacts to either end of the molecule. From our
      experiments we conclude that adsorbed individual DNA molecules have a resistivity
      similar to mica, glass, and silicon oxide substrates. Therefore adsorbed DNA is
      not a conductor, and it should not be considered as a viable candidate for MW
      applications. Parallel studies on other nanowires, including single-walled carbon
      nanotubes, showed conductivity as expected.

PMID- 12070347
TI  - Total arrest of spontaneous and evoked synaptic transmission but normal
      synaptogenesis in the absence of Munc13-mediated vesicle priming.
AB  - Synaptic vesicles must be primed to fusion competence before they can fuse with
      the plasma membrane in response to increased intracellular Ca2+ levels. The
      presynaptic active zone protein Munc13-1 is essential for priming of
      glutamatergic synaptic vesicles in hippocampal neurons. However, a small
      subpopulation of synapses in any given glutamatergic nerve cell as well as all
      gamma-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1.
      We show here that Munc13-2, the only Munc13 isoform coexpressed with Munc13-1 in
      hippocampus, is responsible for vesicle priming in Munc13-1 independent
      hippocampal synapses. Neurons lacking both Munc13-1 and Munc13-2 show neither
      evoked nor spontaneous release events, yet form normal numbers of synapses with
      typical ultrastructural features. Thus, the two Munc13 isoforms are completely
      redundant in GABAergic cells whereas glutamatergic neurons form two types of
      synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas
      the other type employs Munc13-2 as priming factor. We conclude that Munc13
      mediated vesicle priming is not a transmitter specific phenomenon but rather a
      general and essential feature of multiple fast neurotransmitter systems, and that
      synaptogenesis during development is not dependent on synaptic secretory
      activity.

PMID- 12070348
TI  - The aspartate-257 of presenilin 1 is indispensable for mouse development and
      production of beta-amyloid peptides through beta-catenin-independent mechanisms.
AB  - To differentiate multiple activities of presenilin 1 (PS1), we generated
      transgenic mice expressing two human PS1 alleles: one with the aspartate to
      alanine mutation at residue 257 (hPS1D257A) that impairs the proteolytic activity
      of PS1, and the other deleting amino acids 340-371 of the hydrophilic loop
      sequence (hPS1Deltacat) essential for beta-catenin interaction. We show here that
      although hPS1Deltacat is fully competent in rescuing the PS1-null lethal
      phenotype, hPS1D257A does not exhibit developmental activity. hPS1D257A also
      leads to the concurrent loss of the proteolytic processing of Notch and beta
      amyloid precursor protein (APP) and the generation of beta-amyloid peptides
      (Abeta). Further, by measuring the levels of endogenous Abeta(X-40) and Abeta(X
      42) in primary neuronal cultures, we confirmed the concept that PS1 is
      indispensable for the production of secreted Abeta.

PMID- 12070349
TI  - In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide
      based therapeutic substance class.
AB  - Spiegelmers are high-affinity l-enantiomeric oligonucleotide ligands that display
      high resistance to enzymatic degradation compared with d-oligonucleotides. The
      target binding properties of Spiegelmers can be designed by an in vitro-selection
      process starting from a random pool of oligonucleotides. Applying this method, a
      Spiegelmer with high affinity (K(D) = 20 nM) for the peptide hormone,
      gonadotropin-releasing hormone (GnRH) was isolated. The Spiegelmer acts as an
      antagonist to GnRH in Chinese hamster ovary cells stably expressing the human
      GnRH receptor, and its activity is unchanged by linking to 40-kDa polyethylene
      glycol. In a castrated rat model the Spiegelmer further demonstrated strong GnRH
      antagonist activity, which is more pronounced and persists longer with the
      polyethylene glycol-linked derivative. Furthermore, in rabbits the anti-GnRH
      Spiegelmer was shown to have a very low, possibly negligible immunogenic
      potential. These studies suggest that Spiegelmers could be of substantial
      interest in the development of new pharmaceutical approaches against GnRH and
      other targets.

PMID- 12070350
TI  - Reconstitution in yeast of the Arabidopsis SOS signaling pathway for Na+
      homeostasis.
AB  - The Arabidopsis thaliana SOS1 protein is a putative Na+/H+ antiporter that
      functions in Na+ extrusion and is essential for the NaCl tolerance of plants.
      sos1 mutant plants share phenotypic similarities with mutants lacking the protein
      kinase SOS2 and the Ca2+ sensor SOS3. To investigate whether the three SOS
      proteins function in the same response pathway, we have reconstituted the SOS
      system in yeast cells. Expression of SOS1 improved the Na+ tolerance of yeast
      mutants lacking endogenous Na+ transporters. Coexpression of SOS2 and SOS3
      dramatically increased SOS1-dependent Na+ tolerance, whereas SOS2 or SOS3
      individually had no effect. The SOS2/SOS3 kinase complex promoted the
      phosphorylation of SOS1. A constitutively active form of SOS2 phosphorylated SOS1
      in vitro independently of SOS3, but could not fully substitute for the SOS2/SOS3
      kinase complex for activation of SOS1 in vivo. Further, we show that SOS3
      recruits SOS2 to the plasma membrane. Although sos1 mutant plants display
      defective K+ uptake at low external concentrations, neither the unmodified nor
      the SOS2/SOS3-activated SOS1 protein showed K+ transport capacity in vivo,
      suggesting that the role of SOS1 on K+ uptake is indirect. Our results provide an
      example of functional reconstitution of a plant response pathway in a
      heterologous system and demonstrate that the SOS1 ion transporter, the SOS2
      protein kinase, and its associated Ca2+ sensor SOS3 constitute a functional
      module. We propose a model in which SOS3 activates and directs SOS2 to the plasma
      membrane for the stimulatory phosphorylation of the Na+ transporter SOS1.

PMID- 12070352
TI  - Design of protein struts for self-assembling nanoconstructs.
AB  - Bacteriophage T4 tail fibers have a quaternary structure of bent rigid rods, 3 x
      160 nm in size. The four proteins which make up these organelles are able to self
      assemble in an essentially irreversible manner. To use the self-assembly domains
      of these proteins as elements in construction of mesoscale structures, we must be
      able to rearrange these domains without affecting the self-assembly properties
      and add internal binding sites for other functional elements. Here we present
      results on several alterations of the P37 component of the T4 tail fiber that
      change its length and add novel protein sequences into the protein. One of these
      sequences is an antibody binding site that is used to inactivate phage carrying
      the modified gene.

PMID- 12070351
TI  - MHC class I-dependent Vgamma4+ pulmonary T cells regulate alpha beta T cell
      independent airway responsiveness.
AB  - Mice exposed to aerosolized ovalbumin (OVA) develop increased airway
      responsiveness when deficient in gammadelta T cells. This finding suggests that
      gammadelta T cells function as negative regulators. The regulatory influence of
      gammadelta T cells is evident after OVA-sensitization and -challenge, and after
      OVA-challenge alone, but not in untreated mice. With aerosolized Abs to target
      pulmonary T cells, we now demonstrate that negative regulation of airway
      responsiveness is mediated by a small subpopulation of pulmonary gammadelta T
      cells. These cells express Vgamma4 and depend in their function on the presence
      of IFN-gamma and MHC class I. Moreover, their effect can be demonstrated in the
      absence of alphabeta T cells. This novel type of negative regulation seems to
      precede the development of the adaptive, antigen-specific allergic response.

PMID- 12070354
TI  - Increased competition may promote species coexistence.
AB  - It is a mainstay of community ecology that local exclusion of species will result
      if competitive pressures become too large. The pattern of exclusion may be
      complicated, but the qualitative orthodoxy has changed little since the
      pioneering work of Lotka, Volterra, and Gause--no two species can occupy the same
      niche. Stated in a more precise form, the higher the intensity of interspecific
      competition in an assemblage of species, the fewer the number of species that can
      coexist in perpetuity. We suggest that this orthodoxy results from "linear"
      thinking, and that if the classical equations are formulated more realistically
      with attendant nonlinearities, the orthodoxy breaks down and higher levels of
      competition may actually increase the likelihood that species will avoid
      competitive exclusion. Furthermore, this increased probability of coexistence at
      higher levels of competition is accompanied by characteristic dynamic patterns:
      (i) at lower levels of competition, after all extinction events have occurred,
      remaining species follow irregular chaotic patterns; (ii) at higher levels of
      competition, when most species coexist, all species are entrained in a single
      large limit cycle; (iii) the transient behavior appears to correspond to a
      special case of chaos, uniform phase chaotic amplitude.

PMID- 12070353
TI  - A molecular mechanism of action of theophylline: Induction of histone deacetylase
      activity to decrease inflammatory gene expression.
AB  - The molecular mechanism for the anti-inflammatory action of theophylline is
      currently unknown, but low-dose theophylline is an effective add-on therapy to
      corticosteroids in controlling asthma. Corticosteroids act, at least in part, by
      recruitment of histone deacetylases (HDACs) to the site of active inflammatory
      gene transcription. They thereby inhibit the acetylation of core histones that is
      necessary for inflammatory gene transcription. We show both in vitro and in vivo
      that low-dose theophylline enhances HDAC activity in epithelial cells and
      macrophages. This increased HDAC activity is then available for corticosteroid
      recruitment and predicts a cooperative interaction between corticosteroids and
      theophylline. This mechanism occurs at therapeutic concentrations of theophylline
      and is dissociated from phosphodiesterase inhibition (the mechanism of
      bronchodilation) or the blockade of adenosine receptors, which are partially
      responsible for its side effects. Thus we have shown that low-dose theophylline
      exerts an anti-asthma effect through increasing activation of HDAC which is
      subsequently recruited by corticosteroids to suppress inflammatory genes.

PMID- 12070355
TI  - Barriers to drug discovery and development for Alzheimer disease.
AB  - Alzheimer disease (AD) is a neurodegenerative condition leading to progressive,
      irreversible loss of cognitive and behavioral function. Despite considerable
      investments in neuroscience research, only four drugs, all cholinesterase
      inhibitors, have been approved for the symptomatic management of AD in the United
      States. Although basically safe and modestly effective, these drugs are far from
      ideal, being neither universally efficacious nor disease modifying. AD exacts a
      considerable toll in direct medical costs, quality of life, and caregiver burden
      for persons and society. In addition to the obvious clinical benefit, therapeutic
      agents for AD and related dementias represent a considerable market opportunity
      for the pharmaceutical and biotechnology industries. There are currently 8-10
      million AD sufferers in the seven major pharmaceutical markets. The market will
      grow rapidly in coming decades, as the developed world experiences an enormous
      increase in its elderly population. Given the great need for new therapeutic
      agents to manage and prevent AD, the Institute for the Study of Aging and the
      Fidelity Foundation organized a workshop, "Barriers to the Discovery and
      Development of Drugs for Alzheimer's Disease," to examine ways to expedite drug
      discovery and development. The identified barriers and potential solutions will
      be discussed here and in the accompanying articles in more detail.

PMID- 12070356
TI  - Models and modeling systems in Alzheimer disease drug discovery.
AB  - The rapid pace of neurobiology research has increased the prospects of developing
      drugs to prevent neurodegenerative disorders. Although the goal of delaying the
      onset of brain disorders may be within the grasp of modern medicine, there are
      several critical barriers to progress. Among these is the lack of appropriate
      models and modeling systems for specific neurodegenerative diseases.
      Traditionally, in drug discovery, testing, and development, a combination of
      models is used. These include in vitro, in vivo, transgenic, and other animal
      models. However, each of these models has limitations. In this article, the
      author advocates the use of "in silico" modeling systems, which could complement
      currently available models and enable investigators to simulate alternative
      strategies to modulate neural function in a dynamic interactive mode. Advances in
      computer technology, including increasing speed and memory, and ready access to
      parallel processing systems have made it easier for investigators to develop
      databases for computer abstractions of neural function and dysfunction and to
      begin to develop prototypes for use in complex systems modeling environments.
      Multimodeling systems have been widely used in other areas of science to study
      emergent behavior of complex systems, such as the impact of atmospheric changes
      on weather, flight patterns of birds in a flock, and the behavior of traders in a
      commodities market. Adoption of such approaches should increase understanding of
      the complexities of signal transduction pathways in neural networks and
      accelerate the drug discovery process.

PMID- 12070357
TI  - Clinical trials in AD: are current formats and outcome measures adequate?
AB  - Great strides have been made in the measurement of outcomes and treatment
      efficacy in clinical trials of Alzheimer disease (AD) drugs during the past 25
      years. Several sensitive, reliable, and valid clinical outcome measures have been
      developed. The methodology, trial design, and outcome measures for demonstrating
      symptomatic benefits of an AD drug are now established. However, a greater
      challenge lies ahead. Major advances in fundamental knowledge about the
      pathophysiology of the disease and in animal models have transformed the focus of
      current efforts to developing and testing therapies that may actually slow
      disease progression, delay the onset of symptoms, and even ultimately prevent the
      disease. The long-duration trials that will likely be necessary to demonstrate an
      effect on disease progression will be costly and difficult. Proof-of-concept
      trials and subsequent long-term trials could gain power and efficiency from use
      of biologic markers of underlying disease severity, but currently available
      biologic markers are not ideal. A major barrier to such trials is their size and
      cost. One approach to reducing the cost would be to recruit "enriched" samples of
      subjects who are at greater risk of developing AD during the trial than the
      general, elderly population. The major effort required to screen and recruit
      large numbers of subjects for such trials also contributes to the cost. Probably
      the biggest problem currently is the enormous effort and cost of conducting
      periodic clinical evaluations to determine if subjects have declined or developed
      dementia. Research to develop more efficient assessment methods is clearly
      needed. Data acquisition over the Internet is potentially efficient and
      attractive and may become practical as Internet accessibility increases.

PMID- 12070358
TI  - Barriers to Alzheimer disease drug discovery and development in academia.
AB  - The drug discovery and the drug development processes represent a continuum of
      recursive activities that range from initial drug target identification to final
      Food and Drug Administration approval and marketing of a new therapeutic. Drug
      discovery, as its name implies, is more exploratory and less focused in many
      cases, whereas drug development has a clinically defined endpoint and a specific
      disease goal. Academia has historically made major contributions to this process
      at the early discovery phases. However, current trends in the organization of the
      pharmaceutical industry suggest an expanded role for academia in the near future.
      Megamergers among major pharmaceutical corporations indicate their movement
      toward a focus on end-stage clinical trials, manufacturing, and marketing. There
      has been a parallel increase in outsourcing of intermediate steps to specialty
      small pharmaceutical, biotechnology, and contract service companies. The new
      paradigm suggests that academia will play an increasingly important role at the
      proof-of-principle stage of basic and clinical drug discovery research, in
      training the future skilled work force, and in close partnerships with small
      pharmaceutical and biotechnology companies. However, academic drug discovery
      research faces a set of barriers to progress, the relative importance of which
      varies with the home institution and the details of the research area. These
      barriers fall into four general categories: (1) the historical administrative
      structure and environment of academia; (2) the structure and emphasis of peer
      review panels that control research funding by government and private agencies;
      (3) the organization and operation of the academic infrastructure; and (4) the
      structure and availability of specialized resources and information management.
      Selected examples of barriers to drug discovery and drug development research and
      training in academia are presented, as are some specific recommendations designed
      to minimize or circumvent these barriers. In some cases, precedents established
      by other disease-focused areas may be relevant to Alzheimer disease and related
      disorders, but the overall impact of any changes requires adaptation at the top
      of the administrative structures in academia and funding agencies to support and
      encourage cooperative efforts among faculty investigators.

PMID- 12070359
TI  - Barriers to Alzheimer disease drug discovery and development in the biotechnology
      industry.
AB  - The major barrier to Alzheimer disease (AD) drug discovery and development in the
      biotechnology industry is scale. Most biotechnology companies do not have the
      personnel or expertise to carry a drug from the bench to the market. Much effort
      in the industry has been directed toward the elucidation of molecular mechanisms
      of AD and the identification of new targets. Advances in biotechnology have
      generated new insights into disease mechanisms, increased the number of lead
      compounds, and accelerated biologic screening. The majority of costs associated
      with drug development are in clinical testing and development activities, many of
      which are driven by regulatory issues. For most biotechnology companies, the
      costs of such trials and the infrastructure necessary to support them are
      prohibitive. Another significant barrier is the definition of therapeutic benefit
      for AD drugs; Food and Drug Administration (FDA) precedent has established that a
      drug must show superiority to placebo on a performance-based test of cognition
      and a measure of global clinical function. This restrictive definition is biased
      toward drugs that enhance performance on memory-based tests. Newer AD drugs are
      targeted toward slowing disease progression; however, there is currently no
      accepted definition of what constitutes efficacy in disease progression. Despite
      these obstacles, the biotechnology industry has much to offer AD drug discovery
      and development. Biotechnology firms have already developed essential technology
      for AD drug development and will continue to do so. Biotechnology companies can
      move more quickly; of course, the trick is to move quickly in the right
      direction. Speed may offset some of the problems associated with lack of scale.
      Additionally, biotechnology companies can afford to address markets that may be
      too restricted for larger pharmaceutical companies. This advantage will have
      increasing importance, as therapies are developed to address subtypes of AD.

PMID- 12070360
TI  - Barriers to Alzheimer disease drug discovery and drug development in the
      pharmaceutical industry.
AB  - The drug development process in the pharmaceutical industry has evolved from
      separate programs, specific for each country, into one coordinated, global
      development scheme. As a result, such a development program must meet regulatory
      requirements for all countries in which approval for the new drug will be sought.
      Barriers to Alzheimer disease (AD) drug discovery and development in the
      pharmaceutical industry can be categorized as (1) regulatory, (2) logistical, and
      (3) drug development issues. Some of the regulatory barriers could be overcome by
      international harmonization of guidelines for the development of antidementia
      drugs. The logistical issues can be reduced through international collaboration
      in the conduct of clinical studies, and the developmental issues can be addressed
      by using an expedited drug development plan that not only can reduce the time but
      also the resources required to develop the drug.

PMID- 12070361
TI  - Elderly patients caught in a political argument.

PMID- 12070362
TI  - Judges and politicians want a patients' revolution.

PMID- 12070363
TI  - Nurse who used physical force on a patient to remove a call bell.

PMID- 12070364
TI  - Nutrition and the life cycle 4: the healthy diet for the adult.
AB  - The previous three articles in this series reviewed current nutritional advice to
      help maintain health during pregnancy (Vol 9(17): 1133-8), weaning (Vol 9(21):
      2205-16) and in childhood (Vol 10(1): 26-310. This article reviews current
      thinking on what constitutes a health diet for the individual who has left
      childhood behind, but has not yet encountered many of the changes associated with
      old age. Most people enjoy food, and also believe that a good diet will improve
      their health. This article aims to review current thinking on what constitutes a
      healthy diet for the adult.

PMID- 12070365
TI  - Contribution of multidisciplinary team to pain management.
AB  - A fundamental part of satisfactory acute pain management is the regular and
      objective assessment of the patient's pain. The responsibility for this ongoing
      assessment is generally incorporated into the nursing role. Given the
      multidisciplinary nature of modern health care it is contended that this
      assessment is not the sole obligation of nursing or medical staff and that any
      healthcare professional who is offering treatment of therapy to patients should
      incorporate pain assessment into their treatment plan. This article outlines a
      small research study that assesses the contribution that the multidisciplinary
      team (MDT) makes towards pain management and pain assessment in particular. It
      highlights the importance of pain assessment and the fact that management is a
      multidisciplinary issue.

PMID- 12070366
TI  - Development of clinical guidelines for the sedation of children.
AB  - Young children may be unwilling or unable to cooperate if they are required to
      remain motionless for a prolonged period of time. In the hospitalized child,
      investigative procedures perceived as painful or threatening may need the
      administration of a sedative. Clinical guidelines, within a large teaching
      hospital NHS trust in the North of England, were implemented in an attempt to
      reduce the diversity of the practices of healthcare professionals caring for the
      child requiring sedation. The guidelines were formulated by a multidisciplinary
      team and, in conjunction with active dissemination strategies, resulted in a
      change in practice that included: (1) improved communication and cooperation
      between departments, (2) implementation of starvation times before the
      administration of a sedative, and (3) the appropriate referrals to a senior
      paediatrician to seek advice if contraindications to sedation were identified.
      Audit was integral to the process, facilitating the comparison of actual practice
      with the standards developed from the guidelines and ensuring a continuous
      monitoring programme.

PMID- 12070367
TI  - Are we listening to children's views about their treatment?
AB  - This article examines how the recommendations of a recent report 'Listening to
      Children's Views: The Findings and Recommendations of Recent Research'
      (O'Quigley, 2000) can be used within the healthcare environment in order to
      obtain successfully children's views about their medical treatment. Sometimes,
      the treatment proposed is objected to by the child and, occasionally, the
      approval of the courts is sought in order to allow treatment to proceed. At times
      like this, the child's voice seems muted. These are exceptional cases, but every
      day children's nurses have to look after children of all ages and act as
      advocate, adviser, counsellor and nurse. Autonomy, confidentiality and cultural
      sensitivity are dominant themes in the O'Quigley report. Using these themes, this
      article examines how, and why, children's nurses should adopt these
      recommendations to help ensure that the voices of adolescent children, in
      particular, are both heard and listened to by decision makers.

PMID- 12070368
TI  - Relatives' perceptions of side rail use on the older person in hospital.
AB  - With an increasing emphasis on improving standards in the care of older people,
      the use of physical restraints has received growing attention in the nursing
      literature. Physical restraint use has been likened to abuse as it impedes the
      movement of a person, encourages dependence on staff and denies autonomy. Side
      rails (cot sides, bed rails) can be considered as a physical restrain device. The
      therapeutic use of restraint has not previously been adequately explained.
      Furthermore, there is a dearth of literature examining the personal experience of
      physical restraint use. The Family Interview Guide (Strumpf and Evans, 1988) was
      used to explore perceptions of nine relatives whose family had side rails used
      during their care in an older person ward. The findings of the study suggest that
      while families place value on the perceived safety function of side rails, they
      nonetheless have worries about their use. These pertain to the risk of patient
      entrapment and possible injury. Patients' relatives associated side rails with
      ritualized practice in gerontology and make suggestions for the re-design of side
      rails. The study also highlights the potential for increased family participation
      in the decision to use side rails.

PMID- 12070369
TI  - Legal aspects of consent 2: the different forms of consent.
AB  - Mary, following preoperative medication, was taken to theatre for a biopsy for
      possible breast cancer. When the theatre staff went through their checklist they
      could not find a consent form. The consultant surgeon said that he had seen her
      in the outpatients' department 2 weeks before and she had given a clear consent,
      not only for the biopsy but also for a radical mastectomy should the results show
      that to be necessary. He said that he had no problems with continuing the
      operation. The theatre sister was unsure of the legal position.

PMID- 12070370
TI  - Rosidal K: a short-stretch compression bandage system.
AB  - Management of venous leg ulcers account for a large proportion of the work of
      healthcare professionals, especially for those who are community based.
      Multilayer and long-stretch bandage systems have been used successfully for many
      years in venous leg ulcer management. Rosidal K, a short-stretch bandage, is now
      also becoming more widely accepted in this country as an effective and cost
      effective bandage system. This product focus looks at bandage systems and
      examines the research supporting the use of short-stretch bandages and Rosidal K.

PMID- 12070372
TI  - Confessions of nurses bring the profession into disrepute.

PMID- 12070371
TI  - New benchmarking toolkit reveals nursing's essence.

PMID- 12070373
TI  - Government must allow NHS managers to manage.

PMID- 12070375
TI  - A snapshot view of the impact of chronic pain on adolescents.
AB  - This study provides a snapshot view on the impact that chronic pain has on the
      daily functioning of a small group of adolescents (n = 10). Chronic, severe pain
      in childhood and adolescence is not common, but is increasingly recognized to
      occur and be worthy of treatment. Referrals come from a variety of sources
      including paediatric orthopaedic surgeons, paediatric rheumatologists, paediatric
      neurologists, child psychiatrists, and GPs. Examples of the types of conditions
      seen are complex regional pain syndromes, low back pain, pain caused by
      congenital or degenerative disease and chronic headaches. Additionally, chronic
      pain affects the well-being of the family as well as the adolescent. Many
      adolescents have been unable to attend school for months or years, and their
      educational and social development is impaired. The aim of treatment is to
      rehabilitate the adolescents within the context of their families and to return
      them to school and to participating in normal social activities within the limits
      of their condition.

PMID- 12070374
TI  - Nurse who caused an elderly patient stress and embarrassment.

PMID- 12070376
TI  - Enforcement of statutory duties for health and safety at work.

PMID- 12070377
TI  - Cardiorespiratory physical assessment for the acutely ill: 1.
AB  - This article, the first of two parts, aims to develop core cardiovascular and
      respiratory knowledge and to enhance practice for the practitioner caring for an
      acutely ill patient on a general ward setting. The second part will focus on
      advanced cardiorespiratory assessment. With increasing acuity of illness in
      general ward settings, patients' needs are becoming more complex in terms of
      their nursing and medical management. Nurses must be able to respond to subtle
      clinical signs and symptoms and act appropriately to ensure that a safe, patient
      focused environment is maintained and that the care delivered is evidence-based.
      By increasing knowledge of the theory and practice of nursing physical
      assessment, and the ensuing management, acutely ill patients nursed in general
      ward areas may be provided with timely and appropriate care and may avoid further
      deterioration and an intensive care admission. This article describes core
      physical assessment skills, the normal physiology of the cardiovascular system,
      and the management of cardiovascular and respiratory dysfunction.

PMID- 12070378
TI  - Assisting carers using the ACTION model for working with family carers.
AB  - This article is the first in a series of four that describes recent developments
      in Sweden aimed at promoting partnerships between older people, their families
      and formal service providers. The focus in this article is on the use of
      information and communication technology (ICT) to help family carers to be more
      prepared for their caregiving role. It is based upon the PREP (preparedness,
      enrichment and predictability) model of nursing intervention (Archbold et al,
      1995) which is applied in the context of a major ICT project called ACTION
      (Assisting Carers using Telematics Interventions to meet Older persons' Needs).
      The way in which ACTION has developed is briefly considered and the range of
      interventions used is described. Subsequent articles in the series reflect upon
      users' perceptions of the acceptability of the ACTION approach and a case study
      of the benefits of ACTION is also presented. Finally, the series concludes with
      an article which outlines the development of a call centre which is used to
      complement and augment the ACTION service.

PMID- 12070379
TI  - Paediatric continence in children with neuropathic bladders.
AB  - Over the last 8 years in Nottingham we have been developing a comprehensive
      teaching package for children requiring clean intermittent catheterization. Clean
      intermittent catheterization can be a traumatic procedure to undertake for both
      the child and carers. Our aim is to support the child from home to hospital
      providing a link service from our community colleagues through to the child's
      consultant. Over a number of years we have expanded our knowledge and care,
      writing information booklets and preparing photographic demonstrations of
      techniques and operations which some of our children require. We have now
      developed a communication network for schools, helping them to support these
      children in their daily life.

PMID- 12070380
TI  - Reflections on communicating with non-English-speaking patients.
AB  - Nursing patients who speak no English has ethical, legal and professional
      implications for patients, relatives and healthcare staff. Appropriate
      communication between a patient and members of the healthcare team demonstrates
      respect, and empowers the patient to make healthcare decisions. Without
      appropriate translation, the patient who speaks no English is extremely
      vulnerable. Healthcare professionals have a duty to provide appropriate care for
      all patients, irrespective of nationality and ability to speak English. Issues
      such as empowerment, advocacy and confidentiality need to be considered in
      relation to caring for non-English-speaking patients. The author of this article
      reflects on her lecturer exchange at the University of Barcelona, Spain, and how
      her limited ability to speak Spanish gave rise to considering the needs of non
      English-speaking patients in the medical directorate at the Royal London
      Hospital. This reflection gave rise to working with clinical and university
      colleagues in an attempt to improve communication with non-English-speaking
      patients, thus combining the author's role as a nurse, ethics lecturer and link
      lecturer. Working with clinical and university colleagues gave rise to the
      development of an advocacy/translation box file for use in clinical practice, and
      the formation of a staff-student liaison committee working party to review the
      possibility of student nurses becoming volunteer translators for non-English
      speaking patients.

PMID- 12070381
TI  - The InCare Retracted Penis Pouch: an alternative for incontinent men.
AB  - Urinary incontinence in men is a common problem in the community setting and
      within the acute hospital sectors, as well as for people with learning
      difficulties or those who have a mental illness. There are many causes of
      incontinence, some are the result of surgical intervention, as in post
      prostatectomy urinary incontinence, bladder dysfunction caused by a congenital
      abnormality where the ability to develop bladder control is affected, or as a
      side effect of tranquillizer or other medication. All patients with urinary
      incontinence episodes should have thorough investigation of this problem as it is
      often a sign or symptom of an underlying condition, such as an enlarged prostate,
      urethral stricture, or atomic or naturopathic bladder. Effective bladder voiding
      function must be established before the assessment for any urinary collection
      device. Advice on assessment and treatment modalities can be sought from local
      continence advisers or clinical nurse specialists

PMID- 12070382
TI  - All nurses should be able to provide first aid.

PMID- 12070383
TI  - Ambitious plans for people with learning disabilities.

PMID- 12070384
TI  - Nurses must now be the champions of older people.

PMID- 12070385
TI  - Nurse who failed to show respect for a deceased person.

PMID- 12070386
TI  - Helping patients to master correct inhaler techniques: nursing role.
AB  - The use of inhalers is widespread for asthma and conditions such as chronic
      obstructive pulmonary disease and yet many people have difficulties in mastering
      correct inhaler technique. Elderly people and children have specific problems
      with inhaler use and require both targeted and appropriate help in order to
      improve their inhaler technique and minimize waste of inhaled medication and
      therefore lack of therapeutic effect. Nurses need to be able to not only
      demonstrate correct inhaler technique themselves, but also identify what is going
      wrong and be knowledgeable concerning the various options available. Frequent
      assessment of inhaler technique needs to become a regular feature of health
      promotion for all patients using these devices.

PMID- 12070387
TI  - Philosophical and ethical issues in human organ transplantation.
AB  - Organ transplantation has moved over 30 years from being experimental and heroic
      to being the treatment of choice in many terminal diseases of vital organs, such
      as biliary atresis, which would require a liver transplant, or pulmonary
      fibrosis, which would require a heart/lung transplant. There are now many more
      older and chronically sick people than ever before (Hudak et al, 1998).
      Transplantation offers hope for an improved quality of life. All patients have a
      right to care, although there remains a dichotomy between the holistic model of
      care and the medical model. The UKCC's (1992) Code of Professional Conduct
      informs practice, and clauses 1 and 5 are of particular importance in relation to
      this client group. This article looks at some of the problems patients may
      develop pre- and post-transplant and the support required to overcome or minimize
      these problems. Implications for healthcare staff are considered.

PMID- 12070388
TI  - A falls risk-assessment tool in an elderly care environment.
AB  - Falls are a major cause of morbidity and mortality among older people. In an
      inpatient setting it has been suggested that the introduction of risk-assessment
      tools may be an important way of managing the issue. The study reported in this
      article was carried out in two stages. First, fall incidents were identified
      retrospectively using 'falls incident forms' and nursing notes, and the
      characteristics and management of patients who had fallen were compared with
      those who had not fallen. A risk-assessment tool and care plan were developed and
      evaluated prospectively. By analysing the data in stage one it was found that
      falls incidence reporting was poor and patients who had fallen had more evidence
      of previous falls than those who had not fallen. In stage two staff found the
      risk-assessment tool and care plan easy to complete; however, there was little
      documentation about whether any appropriate interventions, specific to the
      individuals' risk score, were carried out. Appropriate interventions identified
      on the risk-assessment tool were put into place inconsistently. As a result of
      this work the hospital has set up a multidisciplinary group to look at falls
      management.

PMID- 12070389
TI  - Successful ageing: keeping the 'person' in person-centred care.
AB  - This article, based on a paper given at the International Network for Studies
      Concerning Older Adults conference, Brazil, charts the emergence of notions of
      successful ageing, health-related quality of life and person-centred care which
      currently figure prominently in debates about health and social care. It argues
      that these developments reflect the importance given to autonomy and
      independence, values which potentially disadvantage the oldest and frailest
      members of society. It is suggested that there is a need for a more inclusive
      conceptualization of person-centred care, which recognizes the values of
      interdependence and reciprocity.

PMID- 12070390
TI  - Is smoking a cause of erectile dysfunction? A literature review.
AB  - Erectile dysfunction is common, and its prevalence increases with age owing to
      age-related diseases of vascular, hormonal, neurogenic and psychogenic factors. A
      literature review was undertaken to explore the impact of smoking on erectile
      dysfunction. The literature review of 18 studies revealed the detrimental effect
      of smoking on erectile function. Smokers were 1.5 times more likely to suffer
      erectile dysfunction than non-smokers. Men may be unaware of the effect of
      tobacco on erectile function. This literature review presents strong reasons for
      stopping smoking, and highlights the need for education within a comprehensive
      smoking cessation programme. All men should be offered smoking cessation
      treatment which includes nicotine replacement therapy and continued support.
      Randomized controlled trials are needed to explore the effect of smoking and
      smoking cessation on erectile dysfunction.

PMID- 12070392
TI  - 3M Cavilon Durable Barrier Cream in skin problem management.
AB  - Maintaining healthy intact skin is an important issue for many healthcare
      professions. Elderly patients are at particular risk from damage by moisture and
      mechanical forces such as pressure, friction and shear because of age-related
      skin changes. This product focus looks at the skin and describes the changes that
      occur in the older person. It also describes the second product in the 3M Health
      Care skin care range, Cavilon Durable Barrier Cream. This product follows on from
      and complements the success of Cavilon No Sting Barrier Film.

PMID- 12070391
TI  - Legal aspects of consent 3: the duty of care to inform.
AB  - Mrs Pearce was expecting her sixth child. The expected date of delivery was 13
      November 1991. On 27 November when she saw the consultant the baby had still not
      arrived. She begged the doctor to induce her or to carry out a caesarean. He
      preferred to let nature take its course, and explained to her the risks of
      induction and a caesarean section. The baby died in utero sometime between 2 and
      3 December. The delivery of a stillborn baby was induced on 4 December. She
      brought an action alleging that the consultant should have advised her of the
      increased risk of stillbirth as a result of the delay in delivery between 13
      November and 27 November (Pearce v United Bristol Healthcare NHS Trust, 1998).

PMID- 12070393
TI  - Health issues associated with rural communities.

PMID- 12070394
TI  - How do we make the NHS value our services?

PMID- 12070395
TI  - Pressure ulcer care: can we learn from poorer countries?

PMID- 12070396
TI  - Comparison of two skin care regimes for incontinence.
AB  - It is estimated that 30% of nursing home residents may be faecally incontinent,
      with those figures rising to 60% for patients in long-stay hospitals (Royal
      College of Physicians, 1995). Maintaining skin integrity for these patients can
      be complex. With little clinical information to support carers, choosing a skin
      care regime that maintains skin integrity for this high-risk group can be
      difficult. This study aims to compare two recognized skin care regimes, used in
      the cleansing of patients' skin following an episode of incontinence, and their
      impact on patients' skin integrity. A total of 93 patients were recruited to the
      trial from five care of the elderly or dependent service providers. The subjects
      were randomly allocated to either group A (soap and water; n = 49), or group B
      (Clinisan (Vernacare); n = 44). Initially, 33 patients in both groups started
      with healthy skin. However, the results of the final assessment identified only
      17 subjects in group A remaining healthy, compared with 27 in group B.

PMID- 12070397
TI  - Using a new foam dressing in the care of fungating wounds.
AB  - Fungating wounds may present with a number of unpleasant symptoms such as
      malodour, high levels of exudate and pain. The cosmetic appearance of the wound,
      along with these associated symptoms, can be a significant cause of distress to
      patients. As a result of the fact that fungating wounds rarely heal, their
      management is based on symptom control, promoting comfort and maintaining or
      improving the patient's quality of life. The treatment of these wounds is
      generally palliative in nature and often involves the use of dressings or other
      topical products to control symptoms. This case study details the use of a new
      hydropolymer foam dressing (Tielle Plus) in the management of a large fungating
      breast wound. The dressing was clinically and cost effective, nursing staff found
      it easy to use, and the patient found it very comfortable and less noticeable
      under her clothing.

PMID- 12070398
TI  - Treatment of pressure ulcers in a rehabilitation ward.
AB  - This article presents a case study of a patient transferred to a rehabilitation
      unit for elderly people. The aim of the article is to show that, with a dynamic
      and committed multidisciplinary team approach, the prevention and treatment of
      difficult pressure ulcers can be achieved in an ever increasingly frail elderly
      population. The article will discuss the methods used to treat and tackle the
      challenges that staff encounter when treating these patients.

PMID- 12070399
TI  - The importance of patients' nutritional status in wound healing.
AB  - Good nutritional status is essential for wound healing to take place. Ignoring
      nutritional status may compromise the patient's ability to heal and subsequently
      prolong the stages of wound healing. Glucose provides the body with its power
      source for wound healing and this give energy for angiogenesis and the deposition
      of new tissue. Therefore, it is vital that the body receives adequate amounts of
      glucose to provide additional energy for wound healing. Fatty acids are essential
      for cell structure and have an important role in the inflammatory process. Wound
      healing is dependent on good nutrition and the presence of suitable
      polyunsaturated fatty acids in the diet. Protein deficiency has been demonstrated
      to contribute to poor healing rates with reduced collagen formation and wound
      dehiscence. High exudate loss can result in a deficit of as much as 100g of
      protein in one day. This subsequently needs to be replaced with a high protein
      diet. Vitamins are also important in wound healing. Vitamin C deficiency
      contributes to fragile granulation tissue. There is a correlation between low
      serum albumin and body mass index (BMI) and the development of pressure ulcers.
      Also, low serum albumin and high Waterlow score have a positive association. The
      body automatically renews tissue while we are asleep but this does not mean that
      protein synthesis does not take place during our wakeful hours. Holistic
      assessment of nutrition and early detection of malnutrition are essential to
      promote effective wound healing.

PMID- 12070400
TI  - Prevention of pressure damage at the Queen's Medical Centre.
AB  - The Wound Management Policy Group is a sub-committee of the Nursing and Midwifery
      Development Group and has an important role at Queen's Medical Centre, both in
      providing support to the tissue viability clinical nurse specialist and in
      providing a multiprofessional perspective on the development and evaluation of
      policies, protocols, strategies and guidelines in all aspects of tissue
      viability. The four major recent projects are: the Nottingham Wound Care
      Formulary and wound management guidelines; the strategy for the prevention and
      management of pressure damage; the policy and procedure for obtaining pressure
      relieving equipment; and the development of group protocols. These projects are
      described below. The Wound Management Policy Group promotes the use of evidence
      based practice across Queen's Medical Centre to ensure the provision of high
      quality care in all aspects of wound management.

PMID- 12070401
TI  - Esprit HR: something safe to lie on.

PMID- 12070402
TI  - Reflections on wound care in Australia.

PMID- 12070403
TI  - New developments in the use of dressings on surgical wounds.

PMID- 12070404
TI  - [Is there still a need for liver biopsy in chronic hepatitis C?].

PMID- 12070405
TI  - [Perspectives in hepatology research].

PMID- 12070406
TI  - [Liver transplantation with cavoportal or renoportal anastomosis: a solution in
      cases of diffuse portal thrombosis].
AB  - OBJECTIVE: Liver transplantation was contraindicated in patients with diffuse
      thrombosis of the portal vein until the recent use of graft portal vein
      reperfusion with the caval flow or one of its tributaries. Long term results of
      these procedures are reported here. PATIENTS AND METHODS: Eight patients with
      diffuse portal vein thrombosis were transplanted by portal reperfusion via latero
      terminal anastomosis between the native caval vein and the graft portal vein (2
      patients) or termino-terminal between the native left renal vein and the graft
      portal vein (6 patients). RESULTS: Three patients died 3, 3 and 6 months
      following transplantation from intracerebral hemorrhage, cardiac arrest, and
      chronic rejection respectively. Three patients had complicated portal
      hypertension. Five patients were alive at home with a median follow-up of 9
      months (2 to 37 months) with normal liver and kinase functions. CONCLUSION:
      Portal reperfusion with the caval vein flow allows transplantation of patients
      with diffuse poral vein thrombosis. According to our experience and to the
      analysis of the literature, reno-portal anastomosis is preferable to cavo-portal
      reconstruction.

PMID- 12070407
TI  - [Natural history, prevention and treatment of hepatitis C virus after liver
      transplantation].

PMID- 12070408
TI  - [Is irritable bowel syndrome a latent form of celiac disease?].

PMID- 12070409
TI  - [Medical demography: the case of hepato-gastroenterology. Introduction to a
      debate].

PMID- 12070410
TI  - Effect of pantoprazole versus other proton pump inhibitors on 24-hour
      intragastric pH and basal acid output in Zollinger-Ellison syndrome.
AB  - AIM: In this open prospective study, the efficacy of pantoprazole in reducing
      gastric acid secretion in Zollinger-Ellison syndrome patients was compared to
      that obtained previously with other proton pump inhibitors. METHODS: Eleven male
      patients previously treated with omeprazole (n=7, mean dosage: 63 mg/day; range:
      20-100 mg/day) or lansoprazole (n=4, mean dosage: 75 mg/day; range: 30-120
      mg/day) were included. These patients underwent a 24-hour intragastric pH-metry,
      measurement of basal acid output and of serum gastrin first while receiving their
      usual therapy and second after 7 to 10 days of pantoprazole treatment at a mean
      dosage of 116 mg/day (range: 40-200 mg/day). Basal acid output was evaluated
      after each intragastric pH-metry, one hour before the next intake of proton pump
      inhibitor and a serum gastrin curve was determined according to 9 fixed time
      points. RESULTS: One patient dropped out before the second intragastric pH-metry
      due to an adverse event (varicella) unrelated to pantoprazole and was
      reinvestigated thereafter. The median 24-h intragastric pH with pantoprazole was
      not significantly different than that with the other proton pump inhibitors (5.3
      versus 4.6, respectively; P=0.90). Neither the median basal acid output values
      nor the median serum gastrin levels were significantly different between
      pantoprazole and the other proton pump inhibitors. CONCLUSION: In these patients
      with the Zollinger-Ellison syndrome, pantoprazole was well tolerated and equally
      effective to the other proton pump inhibitors in terms of antisecretory potency.

PMID- 12070411
TI  - [Value of endoscopic ultrasonography and somatostatin receptor scintigraphy in
      the preoperative localization of insulinomas and gastrinomas. Experience of 54
      cases].
AB  - AIM: The classic morphological techniques for the localization of insulinomas and
      gastrinomas are of limited value. Endoscopic ultrasonography and somatostatin
      receptor scintigraphy have shown high sensitivity for the detection of
      gastroenteropancreatic endocrine tumors. The aim of the study was to evaluate the
      sensitivity of endoscopic ultrasonography and that of somatostatin receptor
      scintigraphy in the localization of insulinomas and gastrinomas. PATIENTS AND
      METHODS: This retrospective study concerned 54 patients with insulinoma (n=29) or
      gastrinoma (n=26) operated on between March 1991 and March 2000 and who had at
      least one among the two tested examinations. Forty-two patients had scintigraphy
      (17 with insulinoma, 25 with gastrinoma), 47 had endoscopic ultrasonography (28
      with insulinoma, 17 with gastrinoma). One of the ten patients with MEN 1 had both
      tumors. All diagnosis were confirmed by histologic examination. RESULTS: The
      sensitivity of scintigraphy for the localization of insulinomas was 47%. There
      was one false positive. Sensitivity of endoscopic ultrasonography for insulinomas
      was 85%. The sensitivity of scintigraphy in the detection of gastrinomas was 65%
      for the tumors in the duodenopancreatic area, 20% for the tumors in the
      pancreatic tail and 71% for metastasis. The sensitivity of endoscopic
      ultrasonography was 46% for duodenal tumors, 75% for pancreatic tumors and 57%
      for lymph node metastasis. The combination of both localization studies increased
      sensitivity to 94%. CONCLUSION: Endoscopic ultrasonography and somatostatin
      receptor scintigraphy are the gold standard for localization of gastrinomas.
      Association of both examinations increases the sensitivity. Scintigraphy for the
      detection of insulinomas should be performed when endoscopic ultrasonography is
      negative.

PMID- 12070412
TI  - [Compared azathioprine efficacy in ulcerative colitis and in Crohn's disease].
AB  - AIM: To compare the 6-month efficacy and tolerance of azathioprine in 68 patients
      with steroid-resistant or steroid-dependent chronic ulcerative colitis (n=30) or
      Crohn's disease (n=38). METHODS: Clinical remission was defined as a Crohn's
      Disease Activity Index<150 for Crohn's disease and number of non-bloody
      stools<=3/day for ulcerative colitis, associated with prednisone requirement<=10
      mg/day. RESULTS: Seventy-three per cent of patients with ulcerative colitis had
      distal or left-sided colitis and 84% of patients with Crohn's disease had
      pancolitis. Azathioprine was discontinued early for side-effect in 8 (26.7%)
      patients with ulcerative colitis and in 8 (21.1%) patients with Crohn's disease
      (NS). In patients treated at least 6 months by azathioprine, clinical remission
      rates were 77.3% and 70% for chronic ulcerative colitis and Crohn's disease (NS).
      Complete corticosteroids weaning was obtained significantly more often in
      ulcerative colitis patients than in Crohn's disease patients (59.1% vs 30%;
      P<0.05). CONCLUSION: Azathioprine seems to be at least as effective and equally
      tolerated in steroid-resistant or steroid-dependent chronic ulcerative colitis or
      Crohn's disease patients.

PMID- 12070413
TI  - [Management of bowel obstruction in advanced abdominal or pelvic cancer].

PMID- 12070414
TI  - [Induced interstitial pneumonitis: role of pegylated interferon alpha 2b].
AB  - Pulmonary complications of alpha interferon are rare. We report two cases of lung
      complications in liver transplantation patients for HCV related cirrhosis. After
      switching from interferon alpha to pegylated interferon alpha 2b, one patient
      developed a BOOP (Bronchiolitis Obliterans Organizing Pneumonia) and the other
      severe interstitial pneumonitis. We discuss the causes of these rare pulmonary
      alpha-interferon induced complications and the different way to suggest that the
      pegylated interferon alpha 2b could be related to the risk of pulmonary toxicity
      of this treatment.

PMID- 12070415
TI  - [Buerger's disease or thromboangiitis obliterans revealed by an enteric ischemia.
      Case report and literature review].
AB  - Thromboangiitis obliterans or Buerger's disease is a rare arteritis affecting
      mainly young male smokers. Distal limb symptoms are well-known. Digestive
      manifestations, especially when inaugural, are less known and sometimes
      misdiagnosed. We report the case of a 37-year-old man who developed a large
      mesenteric infarct with diffuse ischemic colitis and ischemia in the hepatic
      artery field. Histopathological findings were consistent with thromboangiitis
      obliterans. Unexplained abdominal pain, even if inaugural, in young male smokers,
      should evoke the possibility of Buerger's disease.

PMID- 12070416
TI  - [Acute tubular necrosis with acute renal failure during the first month of
      treatment with 5-amino-salicylate (Pentasa(R))].
AB  - We report a case of acute tubular necrosis in a patient with Crohn's disease
      treated by 5-amino-salicylate (Pentasa(R)) since one month. Normalization of
      renal biological parameters occurred rapidly after treatment withdrawal. This
      case raises the question of the optimal modalities of monitoring of renal
      function during treatment with 5-amino-salicylate.

PMID- 12070417
TI  - [Subfulminant hepatitis associated with nimesulide treatment requiring liver
      transplantation].

PMID- 12070418
TI  - [Unexplained increase in aminotransferases and obstructive sleep apnea syndrome].

PMID- 12070419
TI  - [Helicobacter pylori and granulomatous gastritis].

PMID- 12070420
TI  - [Ileal duplication is an uncommon entity in adults].

PMID- 12070421
TI  - [Unintentional ingestion of 30%-formaldehyde in a hospital setting].

PMID- 12070422
TI  - [Laparoscopic colorectal surgery].

PMID- 12070423
TI  - Cyclic nitric oxide release by human granulocytes, and invertebrate ganglia and
      immunocytes: nano-technological enhancement of amperometric nitric oxide
      determination.
AB  - BACKGROUND: Various tissues from vertebrates and invertebrates respond to
      external signal molecules by rapid release of nitric oxide (NO) mediated by
      constitutive nitric oxide synthase. MATERIAL/METHODS: Invertebrate immunocytes
      were collected from maintained stock and human granulocytes were isolated from
      leukocyte-enriched blood obtained from the Long Island Blood Services. The
      invertebrate ganglionic tissue was either extracted or exposed for ex vivo and in
      vivo evaluation. Nitric oxide release was measured using a newly developed NO
      selective nanoprobe, exhibiting enhanced sensitivity. RESULTS: Evaluation of NO
      release from the pedal ganglia of the marine bivalve, Mytilus edulis,
      demonstrated in vitro release of NO that fluctuated from 969 to 1003 pM, with a
      mean change in NO of 35 pM/cycle and a mean cycle time of approximately 4
      minutes. Basal release of NO/cycle from the ganglia in vivo was increased
      significantly to approximately 65 pM (P<0.05) with an increase in cycle time to
      approximately 7 minutes. Exposure of the ganglia to morphine in vivo resulted in
      a significant increase in NO release and a lack of NO pulsations. The fluctuation
      in NO release from immunocytes of Mytilus edulis was approximately 27 pM per
      cycle with a cycle time of 4 minutes whereas human granulocytes release
      fluctuated approximately 23 pM with a cycle time of 6 minutes. CONCLUSIONS: These
      data demonstrate that basal release of NO from various tissues is released in a
      cyclic manner and the cycle time and magnitude is subject to regulation by
      external stimuli.

PMID- 12070424
TI  - Effect of anti-oxidants, free radical quenchers and cyclo-oxygenase inhibitor on
      benzo(a)pyrene-induced suppression of human lymphocyte mitogenesis in vitro.
AB  - BACKGROUND: Benzo(a)pyrene (BP) is a known carcinogen and immunosuppressor.
      Activation of BP to its reactive intermediates is cyclo-oxygenase (COX) dependent
      and occurs via a free radical dependent mechanism. The aim of this study was to
      know whether anti-oxidants, free radical quenchers and (COX) inhibitor,
      indomethacin, influence the suppression of human T cells induced by BP in vitro.
      MATERIAL/METHODS: Human lymphocytes, obtained from healthy human volunteers, were
      stimulated to proliferate using phytohaemagglutinin (PHA). The effect of vitamin
      E, SOD, catalase, mannitol, and COX-inhibitor, indomethacin, on BP-induced
      suppression of human T cell proliferation was evaluated. RESULTS: Except for
      catalase, a hydrogen peroxide (H2O2) radical quencher, none of the agents tested
      could inhibit BP-induced suppression of human T cell proliferation in vitro.
      CONCLUSIONS: BP-induced suppression of human T cell proliferation is probably,
      induced by increased production of H2O2. Prostaglandins and superoxide anion and
      hydroxyl radical do not seem to participate in BP-induced human T cell growth
      suppression.

PMID- 12070426
TI  - Chemoprotection profiles of sodium thiosulfate on methyl methanesulfonate-induced
      mutagenesis of bacteriophage T4.
AB  - BACKGROUND: The alkylation of nucleic acids is primarily responsible for chemical
      carcinogenesis. Even during disease treatment, several alkylating drugs interact
      with nucleic acids and cause severe toxic effects. Thus good chemoprotectants are
      necessary. For our study we chose a simple model organism, bacteriophage T4 (a
      nucleoprotenic particle), and alkylating agent methyl methanesulfonate (MMS) to
      study its lethal effects. Sodium thiosulfate (STS), used as a chemoprotectant,
      has been tested against alkylating drugs. MATERIAL/METHODS: Bacteriophage T4D(o)
      were exposed to different molarities of MMS for several pre-termination
      incubations. Alkylation reactions were stopped with different concentrations of
      STS at given pre-termination incubation periods and further incubated up to 24
      hours. The viability (survival frequency) of phage T4 was studied at various post
      termination intervals by plaque count assay. RESULTS: Our results show that the
      survival frequency is strongly influenced by MMS dosage and exposure time.
      However, the antidotal effect of STS on MMS-induced lethality directly
      corresponds to STS dosage. Survival frequencies with 1% quench solution were
      lower than with 5% quench solution at all molarities of MMS and at different pre-
      and post-termination periods. CONCLUSIONS: Our studies confirmed the role of STS
      in the cytoprotection of bacteriophage T4. In the presence of 1% STS, a moderate
      inhibition in cytotoxicity was observed, while 5% STS exhibited a significant
      inhibition against the cytotoxic activity of MMS, presumably due to a rapid
      covalent binding of the methyl group (carbocation - an electrophile) of MMS with
      the nucleophilic sulfur atom of STS.

PMID- 12070425
TI  - Effects of immunomodulators on acute Trypanosoma Cruzi infection in mice.
AB  - BACKGROUND: Patients who recover from acute trypanosomiasis may succumb to
      chronic Chagas' disease later in life due to age related immunosuppression,
      immune system disorders such as AIDS, or during periods of immunosuppressive
      therapy for organ transplantation. In this study, effects of immunomodulators
      with diverse properties were examined on the course of an acute and lethal
      Trypanosoma cruzi infection. MATERIAL/METHODS: ICR (Swiss) mice inoculated with
      Tulahuen (lethal) strain of T. cruzi were treated with 6 different
      immunomodulators and the course of infection was studied. RESULTS: Tacrolimus (FK
      506) and dexamethasone increased parasitemia in mice when compared to infected
      untreated animals. Mycophenolate mofetil (RS-61443) and recombinant interleukin
      15 (IL-15) treatment decreased the number of parasites but had no effect on
      animal survival. In contrast, compound L-685-818 (tacrolimus analog) and CD40
      ligand (CD40L), provided protection against lethal infection. Mice that survived
      initial infection were all protected against reinfection. CONCLUSIONS: This study
      demonstrates the dangers of immunosuppression with tacrolimus and dexamethasone
      in T. cruzi infected subjects. While mycophenolate did not exacerbate the
      infection, our data suggest potential therapeutic applications for L-685-818 and
      CD40 ligand in trypanosomiasis.

PMID- 12070427
TI  - Human leptin administered intraperitoneally stimulates natriuresis and decreases
      renal medullary Na+, K+-ATPase activity in the rat -- impaired effect in dietary
      induced obesity.
AB  - BACKGROUND: Leptin, produced by adipose tissue, apart from regulating food intake
      and energy expenditure, also has natriuretic activity. In this study we examined
      the effect of leptin on renal Na+, K+-ATPase responsible for active tubular
      sodium reabsorption, and compared the renal effects of leptin in lean and obese
      rats. MATERIAL/METHODS: Male Wistar rats were either kept on normal laboratory
      chow or made obese by a high-calorie diet. The animals were placed in metabolic
      cages and urine was collected in 2-hour periods. RESULTS: In lean animals, leptin
      (1 mg/kg i.p.) caused a 139.5% increase in urine output, a 112.4% increase in
      natriuresis, and a 57.2% increase in the fractional excretion of sodium, but had
      no effect on the glomerular filtration rate. Leptin at this dose decreased renal
      medullary Na+, K+-ATPase activity at 30 minutes, 1 hour and 2 hours by 31%, 34.3%
      and 21.2%, respectively. The effect of leptin on Na+, K+-ATPase at 1 hour was
      dose-dependent; the lowest dose inducing significant inhibition was 0.25 mg/kg.
      By contrast, leptin had no effect on either cortical Na+, K+-ATPase or the
      ouabain-resistant fraction of ATPase. In obese rats, leptin increased urine
      output by only 29.1% and natriuresis by 28.9%, and had no significant effect on
      medullary Na+, K+-ATPase. CONCLUSIONS: Leptin stimulates natriuresis primarily by
      inhibiting tubular sodium reabsorption. This effect is mediated, at least
      partially, by decreased Na+, K+-ATPase activity in the renal medulla, and is
      impaired in obese rats.

PMID- 12070428
TI  - Effect of ambroxol on ion transport -- a model study.
AB  - BACKGROUND: Effect on ambroxol on reflexive physiological reactions of isolated
      frog skin was studied with electrophysiological methods designed to assess ion
      currents occurring in epithelial tissues or organs. The experiments permitted to
      analyze an effect of ambroxol on regulatory mechanisms, which in turn influence
      the constant electrical potential defined as PD and reversible changes of this
      potential during mechanical stimulation (marked as dPD). A contribution of sodium
      and chloride ions transport to the value of transepithelial electrical potential
      of frog skin (before and after ambroxol administration) has been demonstrated
      using amiloride - a blocker of sodium ion transport and bumetanide - a blocker of
      chloride ion transport. MATERIAL/METHODS: The experimental material comprised 34
      fragments of hybrid frog (Rana esculenta L.), representing 14 specimens. The
      experiments involved measuring the transepithelial electrical potential (PD in
      mV) on an isolated frog skin placed in an Ussing apparatus. RESULTS: It has been
      demonstrated that ambroxol influences the processes of ion transport (dPD) which
      in turn depend on mechanical stimulation. The reaction of hyperpolarization
      decreased immediately after administration of ambroxol to the stimulating fluid,
      when transepithelial transport of sodium ion was maintained in the preparations
      studied. Consequently, no effect of ambroxol on the frog skin incubated with
      amiloride was recorded. CONCLUSIONS: It has been demonstrated, based on the
      experiments carried out in the present study, that ambroxol can modify processes
      of ion transport related to activation of sensory receptors. In particular, it
      can influence the stimulated transepithelial sodium ion transport in frog skin.

PMID- 12070429
TI  - Intervention in patients with pneumothorax immediately following CT-guided fine
      needle aspiration of pulmonary nodules.
AB  - BACKGROUND: The incidence of pneumothorax (PTX) as a complication of computerized
      tomography guided fine needle aspirates (CT-FNA) of solitary pulmonary nodules
      (SPN) varies from 8-61%. It has been suggested that the practice of obtaining a
      delayed chest radiograph in patients who have undergone CT-FNA of SPN is not cost
      effective and adds little information concerning lung expansion obtained by CT at
      the end of the procedure. It, however, is not known what percent of patients with
      a PTX present immediately after CT-FNA but do not require prompt chest tube
      placement will progress and require intervention later. MATERIAL/METHODS: One
      hundred-fifty-eight consecutive patients undergoing CT-FNA of SPN were included
      in the study. Immediately after CT-FNA each patient was reimaged with the CT
      scanner to check for PTX. Patients with a PTX immediately after CT-FNA were
      assessed as to whether intervention was undertaken or whether the PTX enlarged
      and/or required drainage at a later time. RESULTS: Thirty-eight patients
      developed a PTX while still on the CT scanner. Twenty-nine patients with an
      immediate PTX did not require drainage of their pleural space. Chest tube
      placement was required promptly after the CT-FNA in 4 patients. Five patients had
      their pleural space drained at a later time due to an increasing size of the PTX
      and/or the development of symptoms attributed to the PTX. CONCLUSIONS: These data
      suggest that patients who develop a PTX immediately after CT-FNA but who do not
      require prompt pleural space evacuation should be followed closely both
      clinically and radiographically.

PMID- 12070430
TI  - Dyspnea scales as a measure of health-related quality of life in patients with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common interstitial
      lung disease and is usually associated with a poor prognosis. IPF patients have a
      significant impairment in health-related quality of life (HRQL), both in terms of
      physical and psychological functioning. A substantial number of dyspnea scales
      are available to clinicians for clinical and research use. The objective of the
      present study was to investigate how some commonly used dyspnea scales correlate
      with measurements of HRQL in IPF patients. MATERIAL/METHODS: A group of 30
      patients with IPF who attended a specialized outpatient respiratory clinic were
      interviewed during a stable period of the disease. HRQL was assessed by the SF-36
      questionnaire. Dyspnea was measured by the baseline dyspnea index (BDI), Modified
      Medical Research Council Scale (MRC), Oxygen Cost Diagram (OCD), clinical element
      of the Clinical, Roentgenographic and Physiologic score (CRP), and a new dyspnea
      scale (NS) based on estimates of required oxygen consumption for usual
      activities. RESULTS: Patients showed impairments in all HRQL domains except the
      Pain Index. All dyspnea scales showed significant correlations with both physical
      and mental HRQL domains. The highest Spearman's coefficients between dyspnea
      ratings and SF-36 components were obtained using the BDI. CONCLUSIONS: Dyspnea
      ratings correlate with HRQL measurements in IPF patients. Dyspnea scales can be
      used as a measure of HRQL in special circumstances.

PMID- 12070431
TI  - Further arguments against including trisialo-Fe2-transferrin in carbohydrate
      deficient transferrin (CDT): a study on male alcoholics and hazardous drinkers.
AB  - BACKGROUND: We attempted to determine whether including trisialo-Fe2-transferrin
      in carbohydrate-deficient transferrin (CDT) affects the diagnostic accuracy of
      CDT as a marker of chronic excessive alcohol intake. MATERIAL/METHODS: The
      criterion standard tests for the diagnosis of alcoholism and alcohol intake were
      the Composite International Diagnostic Interview (CIDI) and the Timeline
      Followback (TLFB). The study groups (alcohol intake in each of the last 4 weeks
      before blood sampling) were comprised of 56 controls (< or = 280 g/week, no
      alcoholism), 54 hazardous drinkers (>280 g/week, no alcoholism), 63 alcoholics
      (>280 g/week, alcoholism diagnosis). CDT analysis was performed with %CDTri-TIA,
      which includes about 50% of trisialo-Fe2-transferrin in CDT, and ChronAlcoI.D,
      which excludes this transferrin isoform from CDT. RESULTS: Depending on the cut
      offs for the CDT/transferrin ratio (upper or lower limit of the test-specific
      borderlines) and on the patient group, the diagnostic sensitivity was 28.1%-72.3%
      for %CDTri-TIA, as opposed to 50.0%-82.5% for ChronAlcoI.D. The diagnostic
      accuracy was 62.8%-78.5% for %CDTri-TIA and 71.8%-86.6% for ChronAlcoI.D. The
      latter test consistently showed higher diagnostic sensitivity and accuracy than
      %CDTri-TIA. The diagnostic specificity was 85.7%-98.2% for %CDTri-TIA and 91.1%
      92.2% for ChronAlcoI.D. The areas under the ROC curve were 0.810%-0.885 for
      %CDTri-TIA and 0.867%-0.896 for ChronAlcoI.D. CONCLUSIONS: The present study and
      data from the literature indicate that including parts of trisialo-Fe2
      transferrin by the %CDTri-TIA test significantly reduces the diagnostic
      sensitivity and thus accuracy of CDT as a marker of chronic excessive alcohol
      use.

PMID- 12070432
TI  - Oxidative stress in the blood of patients with alcohol-related liver cirrhosis.
AB  - BACKGROUND: Ethanol may increase the production of reactive oxygen species (ROS)
      in the liver, which results in the development of alcoholic liver disease (ALD).
      Cytokine-activated blood leukocytes may also participate in this process. The aim
      of our study was to evaluate the oxidative stress level in the blood of patients
      with alcoholic liver cirrhosis. MATERIAL/METHODS: Blood neutrophils from 16
      patients with compensated alcoholic liver cirrhosis and 28 patients with
      decompensated were evaluated for their ability to produce superoxide anion and
      hydrogen peroxide spontaneously and after PMA induction, in comparison to
      controls (16 healthy persons). Serum catalase (CAT), superoxide dismutase (SOD)
      and glutathione peroxidase (GPx) activity were also measured in both groups of
      patients and in the controls. RESULTS: The neutrophils from patients with
      compensated liver cirrhosis spontaneously produced a normal level of O2*- and a
      high level of H2O2, but exhibited a defect in PMA-induced O2*- production. The
      neutrophils from patients with decompensated liver cirrhosis spontaneously
      produced more O2*- and H2O2 than the controls, but the PMA response was weak.
      There were no changes in the expression of GPx, but enhanced SOD activity was
      observed in the serum of patients with decompensated alcoholic liver cirrhosis.
      Increased CAT activity was detected only in serum from patients with compensated
      liver cirrhosis. CONCLUSIONS: These data point to oxidative stress in the blood
      of patients with decompensated alcoholic cirrhosis, since increased resting
      production of ROS in neutrophils was not accompanied by increased GPx and CAT
      activity in serum.

PMID- 12070433
TI  - Atherosclerosis risk factors in children and adolescents with or without family
      history of premature coronary artery disease.
AB  - BACKGROUND: Although coronary artery disease (CAD) becomes symptomatic much later
      in life, the early identification and modification of risk factors may reduce its
      later incidence. MATERIAL/METHODS: 100 subjects 2-18 years old, evenly divided by
      sex, were randomly selected from among children of patients suffering from
      premature myocardial infarction (<55 years); the controls were 100 age- and sex
      matched subjects without a similar family history. In the Pediatric Preventive
      Cardiology Clinic at the Isfahan Cardiovascular Research Center, the subjects
      completed a special questionnaire consisting of anthropometric data, blood
      pressure, skinfold thickness, rate of physical activity, and active or passive
      cigarette smoking. Fasting venous blood was analyzed for serum lipids,
      lipoproteins fibrinogen, and apolipoproteins A1 and B100. The data were analyzed
      with SPSS V6/win using the independent t-test, Kruskal-Wallis, chi-squared, and
      standard linear multiple regression tests. RESULTS: The data showed higher
      prevalence of some major and new risk factors in the experimental group than in
      the controls. The mean total cholesterol, LDL-C, TG, fibrinogen and Apo B100 were
      significantly higher in the experimental group, while the mean values of HDL-C
      and Apo A1 were significantly lower. The differences in terms of Body Mass Index,
      percentage body fat, rate of regular physical activity, and active and passive
      smoking were not significant between groups. CONCLUSIONS: Major and new CAD risk
      factors should be identified and modified as early as possible in children with
      high family risk by screening and health education at an early age.

PMID- 12070434
TI  - The renin-angiotensin-aldosterone system (RAAS) and its relation with calcium
      homeostasis in male obesity.
AB  - BACKGROUND: The aim of our study was to determine whether alterations of the
      vitamin D-endocrine system and the renin-angiotensin-aldosterone system occur in
      male obesity and influence each other. MATERIAL/METHODS: 32 obese male subjects
      and 21 age-matched healthy male subjects were enrolled in the study. The
      parameters measured included serum total calcium (Ca), ionized calcium, magnesium
      (Mg), phosphorus (P), 25-hydroxyvitamin D (25-OHD), supine and upright
      aldosterone and renin activity, and urinary calcium, magnesium, and phosphorus.
      RESULTS: Serum total Ca and ionized calcium were slightly, but not significantly
      lower in obese subjects compared to controls, whereas serum magnesium phosphorus
      and PTH levels were significantly higher in the obese subjects. Mean urinary
      calcium and Mg were not significantly different, while urinary P was
      significantly higher in obese subjects. Mean serum 25OHD was significantly lower
      in obese subjects. Supine and upright aldosterone and renin were unrelated to BMI
      or fat mass. Supine aldosterone correlated with serum total calcium, ionized
      calcium and supine renin activity, but not with other minerals, PTH or 25OHD,
      whereas upright aldosterone did not correlate with other parameters. Supine renin
      activity did not correlate with any parameters, whereas upright renin correlated
      with serum Mg and PTH. There were significant correlations between PTH and BMI or
      fat mass. Urinary Mg was also related to both BMI and fat mass. CONCLUSIONS: Male
      obesity is associated with increased serum Mg, P, PTH and urinary P and lower
      supine aldosterone and 25OHD, but unchanged serum and urinary Ca.

PMID- 12070435
TI  - Symptomatic annular pancreas in newborns.
AB  - BACKGROUND: The pancreas exhibits various types of anomalies, including aplasia,
      dysplasia, pancreatic cysts, duplication, and ectopia, of which the most common
      is annular pancreas. This study describes the characteristic features of 7 cases
      of annular pancreas diagnosed during exploration. MATERIAL/METHODS: Seven
      newborns undergoing surgery for annular pancreas from 1990 to 1998 were analyzed.
      The cases were evaluated according to birth weight, sex, symptoms, methods of
      diagnosis, associated anomalies, and surgical treatment modalities. RESULTS: The
      mean birth weight of the patients was 2385 +/- 1002 g, the mean gestational age
      was 37.5 +/- 3.1 weeks. Four patients (42.8%) had associated anomalies, including
      intestinal malrotation (42.8%), intrinsic duodenal obstruction (28.5%), trisomy
      21 karyotype (14.2%), cardiac malformation (14.2%), and Meckel's diverticulum
      (14.2%). Surgical treatment included duodenoduodenostomy (DD) in four patients
      and DD plus tapering enteroplasty (TE) plus placement of transanastomotic jejunal
      tube (TJT) in three patients. CONCLUSIONS: Infants with annular pancreas
      associated with duodenal obstruction are generally premature or small for their
      gestational age. The symptoms observed in annular pancreas are related not only
      to extrinsic compression of the ectopic tissue, but also the duodenal stenosis
      associated with this malformation. Annular pancreas is most commonly associated
      with intestinal malrotation. It does not correlate as strongly with trisomy 21
      karyotype as do the duodenal atresias, and oral feeding tolerance time is nearly
      the same between the DD and DD+TE+TJT groups.

PMID- 12070436
TI  - Extrahepatic bile duct injury during laparoscopic cholecystectomy -- own
      material.
AB  - BACKGROUND: Despite recognised advantages of laparoscopy, the damage of
      extrahepatic bile ducts during cholecystectomy is a subject of ongoing
      discussions, as such injuries are more frequent comparing with open surgery.
      MATERIAL/METHODS: The analysis included 6873 patients who underwent laparoscopic
      cholecystectomy. The study group comprised both the patients after elective
      surgery due to symptomatic cholelithiasis and patients after emergency procedures
      necessitated by acute cholecystitis. RESULTS: Common bile duct was damaged in 9
      patients. Five people had their main bile duct transected, in 2 people it was
      partial excision, and in the other 2 subjects - puncture damage with
      electrocoagulation took place. In seven cases, the damage was diagnosed still
      during laparoscopy and conversion to open surgery was performed. In two subjects
      the damage was diagnosed in postoperative period and it was subsequently
      confirmed by ERCP. Reconstructive surgery included: CBD suturing with interrupted
      stitches, end-to-end anastomosis over T-tube and Roux-en-Y bilioenteric
      anastomosis. Good postoperative outcome was obtained in 6 patients. One subject
      required repeated endoscopic dilatation and placement due to recurrent
      cholangitis. Two patients died due to upper gastrointestinal bleeding and
      multiple organ failure. CONCLUSIONS: Extrahepatic bile duct injury remains a
      dangerous complication following cholecystectomy. It is more likely to occur in
      case of anomalous anatomy of bile ducts, inflammatory or malignant infiltration
      and technical errors of an operating surgeon. It is very important to diagnose
      the damage early enough, preferably still during laparoscopy. Imaging
      investigations (ultrasound, ERCP, MRCP, cholangiography) may be helpful in
      establishing the diagnosis during the postoperative period.

PMID- 12070437
TI  - Apoptosis and pH of blasts in acute childhood leukemia.
AB  - BACKGROUND: The purpose of our study was to determine whether spontaneous and
      post-initial therapy apoptosis indexes (AI) and the intracellular pH of blasts
      have prognostic value in the treatment of children with acute leukemia.
      MATERIAL/METHODS: Blasts from 38 children with acute leukemia (31 with ALL and 7
      with AML) were tested for apoptotic index (Annexin V) and intracellular pH
      (SNARF). Of the ALL patients, 9 were low risk, 7 medium risk, and 15 high risk.
      Among the AML patients, 1 was low risk and 6 were high risk. Follow-up ranged
      from 6 to 120 weeks (median 60 weeks). RESULTS: The mean spontaneous AI was 19 +/
      16%. The pH of leukemic blasts before treatment varied between 6.6 and 7.9 (mean
      7.2 +/- 0.5). For patients < 10 years old, the markers for good prognosis were a
      WBC count below 50 x 10(3)/microml, good response to prednisone therapy at day 8,
      and remission at or before day 33. Univariate analysis showed that pH < 7 had
      favorable prognostic significance. Overall, the probability of EFS for patients
      with pH < 7 was 1.0, as opposed to 0.49 for those with pH > 7 (p=0.049, n=36).
      The probability of EFS for patients with AI below the median was not
      significantly different from those with AI above the median (0.4 vs 1.0, NS).
      CONCLUSIONS: The assessment of intracellular pH in blasts may be an important
      prognosticator for ALL patients. Children with low spontaneous AI or high pH of
      leukemic blasts appear to have an unfavorable prognosis.

PMID- 12070438
TI  - Pathological somatosensory evoked potentials in patients with hypertension: a
      contribution to the study of the pathophysiology of juvenile essential
      hypertension.
AB  - BACKGROUND: The role of factors influencing the cerebral regulation of blood
      pressure must be considered in the etiopathogenesis of essential hypertension The
      aim of our work was to explore the possibilities for differentiating certain
      clinical, functional and electrophysiological signs in young and adult
      hypertensives. This could help us to determine whether centrally active
      antihypertensive drugs may be more suitable than others. MATERIAL/METHODS: We
      examined somatosensory evoked potentials (latencies of wave deflections and
      amplitudes) in two groups of patients with essential hypertension. The first
      group consisted of 25 hypertensive patients aged 20 to 30 years with onset before
      age 20 (n=25). The second group consisted of 40 hypertensive patients aged 40 to
      60 years with onset after the age of 30. The results were compared with those
      obtained from age-correlated healthy controls. RESULTS: The most interesting
      changes were observed in the amplitudes of somatosensory evoked potentials in the
      group of juvenile patients with hypertension. The decrease in the amplitude of
      all wave deflections was very compact, consistent, and statistically significant
      even after repeated examinations. This finding raises the possibility of
      influence or damage to the peripheral afferentation of signals in juvenile
      patients, with hypertension as an expression of the reactions of brainstem
      structures. CONCLUSIONS: Our results suggest that afferent impulses and the
      reactivity of brainstem structures may play a role in the etiopathogenesis of
      hypertension.

PMID- 12070439
TI  - Incidence and molecular analysis of glucose-6-phosphate dehydrogenase deficiency
      in the province of Denizli, Turkey.
AB  - BACKGROUND: G6PD deficiency is a widespread abnormality of glucose-6-phosphate
      dehydrogenase, a red cell enzyme, which gives rise to hemolysis under oxidative
      stress. In Turkey, G6PD deficiency has a variable frequency in different regions.
      The prevalence and genotypes of G6PD deficiency are not known in Denizli province
      of the Aegean region of Turkey. Accordingly, this study was designed to
      investigate the prevalence of enzyme deficiency and the distribution of the
      Mediterranean mutation of G6PD in this region. MATERIAL/METHODS: A total of 1950
      students (918 females, 1032 males, ages between 14 and 17) were screened by the
      Fluorescent Spot Test, and the G6PD deficiency was confirmed by quantitative
      spectrophotometric assay. The G6PD deficient subjects were further analyzed by
      the PCR/RFLP technique to identify the presence of the 563 T Mediterranean
      mutation. RESULTS: 24 of the subjects were found to be deficient in this enzyme,
      a frequency of 1.23%. Of 24 deficient subjects, 19 (79%) had the 563 T
      Mediterranean mutation. CONCLUSIONS: The frequency of G6PD enzyme deficiency
      appears to be low compared with those found in the malaria-endemic Mediterranean
      region of Turkey. The molecular pathology of G6PD deficiency is related to the
      G6PD-563 T mutation in the Denizli region.

PMID- 12070440
TI  - Does the negative correlation found in breast cancer patients between plasma
      melatonin and insulin-like growth factor-I concentrations imply the existence of
      an additional mechanism of oncostatic melatonin influence involved in defense?
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) is probably involved in
      promoting both normal and neoplastic cell growth, neoplastic transformation
      processes, angiogenesis, and neoplasma progression. On the other hand, one
      possible mechanism of the oncostatic action of melatonin is its influence on the
      action and/or release of the growth factors that stimulate neoplastic cell
      growth. Quantitative changes in melatonin and IGF-I, as well as an imbalance
      between melatonin and IGF-I, may affect the growth of breast cancer cells and
      exacerbate the disease. The aim of our research was to study the interactions
      between plasma melatonin and IGF-I concentrations in pre-menopausal breast cancer
      patients. MATERIAL/METHODS: Our research involved 24 breast cancer patients (mean
      age 43 +/-6) with stage II breast cancer (Bloom and Richardson classification),
      confirmed by histological studies, and were 4 weeks after radical mastectomy. The
      control group consisted of 16 healthy women volunteers (mean age 44 +/- 5).
      RESULTS: No statistically significant relations were found between mean plasma
      melatonin and IGF-I concentrations in the two study groups. In the breast cancer
      group the correlation coefficient between IGF-I concentration in plasma and
      melatonin was r = -0.392 (p = 0.058). CONCLUSIONS: The negative correlation
      between the plasma melatonin and IGF-I concentrations in the breast cancer
      patients we studied could reach statistical significance in a larger population.
      The presence of such a negative correlation between plasma melatonin and IGF-I
      concentrations in patients with neoplastic disease may imply the existence of an
      additional defense mechanism based on the oncostatic influence of melatonin.

PMID- 12070441
TI  - Presentation of intracranial arachnoid cysts in children: correlation between
      localization and clinical symptoms.
AB  - BACKGROUND: The present study was performed in order to determine the most common
      neurological signs of arachnoid cysts (AC) in a pediatric population and to
      evaluate if there is a correlation between the localization of the cyst and the
      clinical characteristics. MATERIAL/METHODS: Forty-five AC patients were studied,
      aged 2-17 years, who were consecutively referred to the Department of
      Developmental Neurology at the Medical University of Gdansk between 1990-2001.
      RESULTS: We found that AC has a strong predilection to the temporal regions and
      was associated with epilepsy in 31% of the cases. The patient's main complaint,
      however, was headache (in 69% of cases). In 6 cases AC required surgical
      treatment, because of intracranial hypertension. The AC concomitant with epilepsy
      had a significant predilection to the left temporal region (92% of cases).
      CONCLUSIONS: The significance of this finding suggests the important role of the
      temporal lobe in the generation of epileptic activity; however, the association
      with the left cerebral hemisphere remains unclear. Although AC localized in the
      middle cerebral fossa are very often asymptomatic, in our opinion in many cases
      they may be the cause of, and have relationship with epilepsy and headaches in
      childhood and adolescence. For this reason MRI studies are necessary in any child
      with epilepsy and headaches of unclear etiology.

PMID- 12070443
TI  - Modulation of the susceptibility of intestinal bacteria to bacteriophages in
      response to Ag43 phase variation -- a hypothesis.
AB  - Escherichia coli is a Gram-negative bacterium which colonizes the intestinal
      tract of man and other animals. In addition to being a part of the normal
      bacterial flora of the human intestine, there are a number of enteropathogenic
      strains of E. coli which cause infections ranging in consequence from diarrhoea
      to colitis. Antigen 43 (Ag43) is the major phase-variable protein in the outer
      membrane of E. coli. One benefit for bacteria resulting from phase variation of
      surface antigens is usually ascribed to evasion of host defences. However,
      results of recent studies indicate that infection of E. coli by different
      bacteriophages is inhibited in the presence of certain bile salts and
      carbohydrates (components present in the human intestine but absent in standard
      bacteriological media) when cells are in the 'OFF' state for production of Ag43.
      The inhibition of bacteriophage development was found to be due to a significant
      impairment in the process of phage adsorption and evidence was presented for the
      binding of phage to Ag43. Here we present a hypothesis that in the case of Ag43,
      phase-variation might benefit the host bacterium by modulating the susceptibility
      to phage infection in the gut. If this hypothesis is true, it may have important
      implications not only for basic research but also for development of
      bacteriophage therapy, a re-discovered method of treatment of patients with
      infectious diseases.

PMID- 12070444
TI  - General model to describe the structure and dynamic balance between different
      human serum lipoproteins and its practical application.
AB  - BACKGROUND: Many dangerous diseases are associated with changes in the
      concentration of blood lipoproteins (LPs). Thus a fast and accurate method is
      needed to determine the composition of lipoprotein fractions in human serum.
      MATERIAL/METHODS: A comparison of 30 parameters characterizing different LPs in
      serum from 120 healthy donors and 102 multiple sclerosis patients was carried out
      using a unique algorithm developed to determine the concentrations of all the
      main lipids and apolipoproteins in each LP fraction and subfraction. Specially
      developed computer programs and the small-angle X-ray scattering (SAXS) method
      were used to analyze the literature and experimental data. RESULTS: A general
      mathematical model has been developed to describe the structure and equilibrium
      between various LPs, from high density to chylomicrons. All human serum LPs can
      be regarded as spherical particles, composed of a lipid hydrophobic spherical
      core consisting of triglycerides and cholesterol esters, and a hydrophilic shell
      of free cholesterol, phospholipids and apolipoproteins. We show for the first
      time that the distribution of components among various LP particles can be
      described by a system of five basic equations and two additional balance
      equations. The observed difference between control subjects and MS patients was
      found to be statistically significant in 23 parameters. CONCLUSIONS: In contrast
      to traditional methods the new method for analyzing human blood LPs is very
      simple and relatively quick.

PMID- 12070442
TI  - Case presentation of gastrinoma combined with gastric carcinoid with the longest
      survival record -- Zollinger-Ellison syndrome: pathophysiology, diagnosis and
      therapy.
AB  - BACKGROUND: Zollinger-Ellison syndrome is a very rare disease caused by tumor
      with gastrin producing cells accompanied by hypergastrinemia leading to gastric
      hypersecretion and peptic ulcers and their complications. CASE STUDY: Female case
      of gastrinoma (Zollinger-Ellison syndrome; Z-E) with a record of 38 yrs of
      survival. Acute gastro-duodenal ulcers started at 28 yr of age and Z-E was
      diagnosed by using gastrin assays. Basal and maximal acid outputs and ratio of
      basal/maximal outputs were away over normal limits. Because of ulcer recurrence
      and complications, patient was subjected to several gastric surgeries but refused
      total gastrectomy. She was also treated with many H2-receptor (R) antagonists and
      proton-pump inhibitors (PPI), each new drug being initially highly effective but
      then showing declining efficacy except when PPI, lansoprazole was used. The
      gastrin level rose in the course of disease from initial high value of 2000 pg/mL
      to the extreme 4500 ng/mL at present. During the last 2 yrs, metastasis mainly to
      liver developed and they were successfully treated by synthetic octapeptide
      derivative of somatostatin and, as a result, metastatis partly reduced and plasma
      gastrin drasticly decreased. Biopsy taken from liver metastasis showed the
      presence of typical gastrinoma cells with gastrin and chromogranin, while that
      from oxyntic mucosa revealed the ECL-cell hyperplasia with carcinoid tumors and
      unexpected gastric atrophy. CONCLUSIONS: This phenomenal case described in this
      article might be the new proven evidence needed by gastroenterologists to
      overturn the traditional treatment using total gastrectomy as a treatment of
      choice to the partial gastrectomy combined with proton pump inhibitors.

PMID- 12070446
TI  - The application of the Mancini technique as a diagnostic test in the CSF of
      tuberculous meningitis patients.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is still a serious cause of morbidity
      and mortality in developing nations, and the timing of treatment is the most
      crucial factor affecting the ultimate outcome. To establish a rapid diagnosis, we
      used Single Radial Immuno-Diffusion (SRID) to detect circulating mycobacterium
      antigen in the CSF of patients with clinically suspected TBM. MATERIAL/METHODS:
      Single radial immunodiffusion is the simplest of all immunotechniques for the
      quantitative determination of antigen or antibody. CSF was collected by standard
      lumbar puncture. Antiserum was raised against CSF from clinically suspected TBM
      patients by standard Immunization procedures. RESULTS: The developed protocol was
      tested with 73 CSF samples collected over a period of one year. The assay gave
      94% sensitivity for the detection of mycobacterium antigen in the CSF of patients
      with clinically suspected TBM. CONCLUSIONS: This study suggests that single
      radial immunodiffusion is useful for quantitative as well as qualitative
      determination of mycobacterium antigen. The developed technique is of potential
      value in the laboratory diagnosis of TBM.

PMID- 12070445
TI  - 18 F-Fluorodeoxyglucose triple-headed coincidence detection imaging in oncology:
      preliminary results and comparison with dedicated PET.
AB  - BACKGROUND: Dual head coincidence (DHC) imaging has been proposed as a valuable
      and cheaper alternative to oncological PET. The increased sensitivity of the
      recently-developed triple-headed gamma camera (THC) optimized for coincidence
      detection has not been either validated or compared to the sensitivity of a
      dedicated PET system in a clinical study. MATERIAL/METHODS: Differences in
      contrast-to-noise-ratio (CNR) between dedicated FDG PET, DHC and THC imaging were
      assessed using a hot sphere phantom. Twenty-two oncological patients were
      prospectively studied with consecutive whole body FDG PET and FDG THC imaging.
      The images were visually read by 2 experienced nuclear medicine specialists. The
      diagnostic sensitivity of FDG THC imaging was assessed using FDG PET as the
      imaging gold standard. Lesion size was determined using computed tomography or
      magnetic resonance imaging. RESULTS: The mean gain in CNR for THC as compared to
      DHC imaging was 35% (10-56%). Of 63 lesions, 58 (92%) on FDG PET were also
      detected with THC imaging. Considering only lesions smaller than 15 mm, the
      relative sensitivity was 86% (24/29). All lesions above 15 mm (n=34) were
      detected using THC imaging. CONCLUSIONS: The first clinical results for THC
      imaging are promising. The overall relative sensitivity in this limited series
      was 92%. Only a few lesions smaller than 15 mm were missed.

PMID- 12070447
TI  - Efficiency of CT-angiography in the diagnosis of intracranial aneurysms.
AB  - BACKGROUND: CT-angiography is a non-invasive method, alternative to cerebral
      angiography in the diagnosis of intracranial aneurysms. The aim of the study was
      the assessment of the efficiency of CT-angiography in a large material, which has
      been mostly verified with angiography and/or surgery. MATERIAL/METHODS: CT
      angiography was performed in 196 patients with intracranial bleeding. Seventy
      three (73) patients underwent also cerebral angiography (CA), 121 were operated
      on, 74 of them solely on the basis of CT-angiography. A spiral CT scanning (2 mm
      slices, 1-1.5 pitch, 1 mm-gap reconstruction) combined with an injection of 120
      mL of contrast medium (5 mL/sec) was used. Subsequently three-dimensional MIP
      reconstructions were received, supplemented in some cases with SSD, VRT and MPR.
      RESULTS: CT-angiography revealed 128 aneurysms in 106 patients, located mostly in
      anterior communicating, middle cerebral and internal carotid arteries. The size
      of most aneurysms was 6-10 mm, but nearly one-third of them did not exceed 5 mm.
      In the group of patients who underwent CA, there was only 1 false negative CT
      angiography result, while in 7 patients CT-angiography allowed for the diagnosis
      of small aneurysms which were not clearly visible on CA. CT-angiography was
      superior to CA in assessment of aneurysm morphology by 3 independent radiologists
      in 17 out of 22 cases. CT-angiography findings were confirmed during surgery in
      all 74 patients. CONCLUSIONS: CT-angiography is highly effective in the diagnosis
      of intracranial aneurysms and the evaluation of their morphology. In our opinion,
      in most cases, CT-angiography is precise enough to plan a surgical or
      endovascular procedure.

PMID- 12070448
TI  - MR in neurological syndromes of connective tissue diseases.
AB  - BACKGROUND: Neurological complications in the course of SLE are mostly associated
      with vascular changes. An important role in their pathogenesis is played by
      immune mechanisms. The aim of the study was to determine the value of modern
      imaging techniques, with special reference to selected MR sequences (FLAIR, DWI)
      in the diagnosis of cerebral changes in patients with neurological symptoms of
      SLE. MATERIAL/METHODS: Fifty patients with neurological symptoms of SLE underwent
      CT and MR of CNS in routine sequences. In 12 cases EPI DWI sequences were also
      performed. Serum levels of antinuclear, anti-native DNA and antiphospholipid
      antibodies were also determined. RESULTS: The changes in CNS were detected in 48
      patients in MR and in 42 patients in CT. Focal changes were observed in 29 cases,
      while atrophic changes were seen in the majority of subjects. In 10 cases, DWI
      showed changes typical for acute stroke. The extend and advancement of changes in
      CT and MR correlated with the severity of neurological symptoms; there was also a
      correlation between the changes and elevated levels of antiphospholipid
      antibodies. FLAIR was useful in the detection of gliosis and cortical scar, while
      DWI enabled us to detect acute ischaemic foci and to distinguish them from
      coexistent scars. CONCLUSIONS: MRI with FLAIR and DWI sequences enhances the
      sensitivity and specifity of neuroimaging techniques in the diagnosis of
      neuropsychiatric disease in SLE. There is a correlation between elevated titre of
      antiphospholipid antibodies and the presence of vascular changes in patients with
      neurological manifestations of SLE.

PMID- 12070449
TI  - Cardiotoxicity following different doses and schedules of 5-fluorouracil
      administration for malignancy -- a survey of 427 patients.
AB  - BACKGROUND: Although cardiotoxicity associated with 5-Fluorouracil (5-FU)
      administration is infrequent, there are case reports of acute coronary syndromes.
      We report on patients undergoing 5-FU chemotherapy who developed cardiac symptoms
      during its administration. MATERIAL/METHODS: In patients receiving 5-FU who
      experienced cardiac-related symptoms, ECG and serum cardiac enzyme determination
      were performed. If cardiotoxicity was detected, 5-FU infusion was interrupted,
      and the patients received sublingual nitrates and cardiac monitoring, while
      patients with more than 2-fold elevated enzyme levels were monitored in a
      coronary care unit for at least 72 hours. In cases of acute myocardial
      infarction, 5-FU was terminated. RESULTS: Of 427 patients entering the study, 17
      (4%) developed clinical symptoms and ECG abnormalities indicating 5-FU
      cardiotoxicity. Patients with continuous infusion (c.i.) of 5-FU had a higher
      incidence of cardiotoxicity (12/197, 6%) than the remaining (5/235, 2.1%)
      (p=0.067), but more toxicity was encountered in patients with c.i. of 5-FU+LV for
      24 hours for 5 days than in patients with the same regimen of 5-FU without LV
      (p<0.027) or patients with short 5-FU+LV administration (p=0.024). Seven of the
      17 patients with 5-FU cardiotoxicity had an acute myocardial infarction, 4
      developed ischemic changes, while 4 more patients had ECG abnormalities
      consistent with coronary vasospasm, of whom one subsequently died. CONCLUSIONS:
      The present study supports the toxic effect of 5-FU on myocardium, which is
      largely schedule-dependent. Considerable vigilance is required when using this
      drug, and its toxic effect on the coronary endothelium and myocardium merit
      further investigation.

PMID- 12070450
TI  - Salvage chemotherapy with the gemcitabine/docetaxel combination in non-small cell
      lung cancer: an overview of recent phase II studies.
AB  - BACKGROUND: Docetaxel has been the only single agent with proven activity and
      documented survival benefit in the second-line treatment of advanced/refractory
      non-small cell lung cancer (NSCLC). Combinations of docetaxel with other active
      agents in this setting, such as gemcitabine, besides their popularity as front
      line treatment, are currently being explored in an attempt to improve the results
      over single-agent docetaxel in relapsed/refractory NSCLC. MATERIAL/METHODS: Given
      the established activity of single-agent docetaxel in two recent large randomized
      phase III trials against best supportive care or versus single-agent Vinorelbine
      or Ifosfamide in patients with platinum pretreated NSCLC, and the proven activity
      of single-agent gemcitabine in this setting, combination regimens employing these
      two agents in various doses and schedules have recently been initiated.
      Adequately designed phase II studies using standard criteria of efficacy and
      safety, with peer-review based publication, were selected from the literature.
      RESULTS: The gemcitabine/docetaxel combination in various schedules with or
      without G-CSF support as salvage therapy of NSCLC pre-treated with
      platinum+paclitaxel-based regimens has been evaluated in four recently published
      phase II clinical studies, and has been shown to represent a tolerable and active
      regimen in this setting, yielding a 10-33% response rate, improvement of disease
      related symptoms, and meaningful median and 1-year survival figures in the range
      of 20-32%. Improvement of disease-related symptoms has outweighed toxicity in all
      these studies. CONCLUSIONS: Randomized studies are warranted, comparing the
      gemcitabine/docetaxel combination to single-agent gemcitabine or docetaxel, drugs
      currently recommended in the second-line treatment of advanced NSCLC.

PMID- 12070451
TI  - Stress-related diseases -- a potential role for nitric oxide.
AB  - Nitric oxide (NO) is involved in stress physiology and stress-related disease
      processes. Like stress, NO seems to be capable of principally exerting either
      beneficial or deleterious effects. The actual distinction depends on a multitude
      of factors. Moreover, NO counteracts norepinephrine (NE) activity and sympathetic
      responsivity. Thus, NO and the stress (patho)physiology are closely connected and
      molecular mechanisms or pathways may be shared under certain conditions. NO is
      involved in immunological, cardiovascular, and neurodegenerative diseases/ mental
      disorders. It represents a 'double-edged sword', since small quantities produced
      by constitutive enzymes may predominantly mediate physiological effects, whereas
      the expression of inducible NO synthases may lead to larger quantities of NO, a
      situation that may be associated with cytotoxic and detrimental effects of NO.
      The key step for normally useful physiological mechanisms becoming
      pathophysiological may be represented by the loss of balance, the loss of control
      over the different pathways induced. A failure to terminate or shift originally
      protective mechanisms may lead to a vicious cycle of disease-supporting
      pathophysiological pathways. CONCLUSIONS: Profound connections between stress and
      various disease processes exist. Thereby, common pathophysiological pathways in
      stress-related diseases have been described, and they involve stress hormone
      (cortisol, NE) and, in particular, NO activity. Thus, NO has detrimental
      capacities. However, NO not only exerts deleterious but also strongly
      ameliorating effects. The balance between both properties is crucial. Yet, nitric
      oxide involvement in stress-related diseases represents a common pathway, with
      various pathophysiological analogies, that may be accessible for strategies using
      stress management and relaxation response techniques.

PMID- 12070452
TI  - Hydrolysis of cortex peptidoglycan during bacterial spore germination.
AB  - Despite the most extreme dormancy and resistance properties among living systems,
      bacterial endospores retain an alert sensory mechanism to respond to the
      germinants and initiate germination. Although the molecular mechanism of the
      germination process is not completely described, current progress in the studies
      on the enzymes involved in the process gave us a somewhat clearer picture of the
      process of spore peptidoglycan (cortex) hydrolysis, a major biochemical event in
      germination. Germination-specific cortex-lytic enzymes require muramic acid d
      lactam in their substrates. At least two types of enzymes are involved in the
      germination process: a spore cortex-lytic enzyme (SCLE) and a cortical fragment
      lytic enzyme (CFLE). Except for their peptidoglycan-binding regions, the primary
      structures of SCLE and CFLE vary according species. Both enzymes differ in their
      hydrolytic bond-specificities and recognition of the substrates morphology. SCLE
      appears to initiate germination by uncrosslinking the intract cortex, and the
      CFLE further degrades the polysaccharide moiety of the SCLE-modified cortex. In
      vivo CFLE activity is likely regulated by its requirement for partially un
      crosslinked cortex, while SCLE requires activation process. Clostridium
      perfringens SCLE is activated by a germination-specific serine protease during
      germination, but the activation mechanism of SCLE in Bacillus species is unknown.
      Cortex-lytic enzymes are expressed at the early stage of sporulation but the
      compartment of expression depends on proteins. However, all enzymes are located
      outside the cortex layer in dormant spores, suggesting that the hydrolysis
      process initiates at the exterior side of the cortex. The assembly of the
      germination apparatus is also discussed.

PMID- 12070453
TI  - Wireless capsule endoscopy -- beyond the frontiers of flexible gastrointestinal
      endoscopy.
AB  - Wireless capsule endoscopy is currently the outstanding technical innovation in
      diagnostic gastrointestinal endoscopy. Especially for small bowel diseases this
      new technique offers several potential advantages compared to traditional
      diagnostic tools. Capsule endoscopy is a painless procedure that can be performed
      as an ambulatory endoscopic examination. First experimental studies proved the
      good tolerance of the capsule endoscopy and the possibility of a complete visual
      investigation of the small bowel. Clinical studies demonstrated possible fields
      of application: Obscure chronic or intermittent gastrointestinal blood loss and
      inflammatory bowel disease. The major risk of the procedure - intestinal
      obstruction by the capsule - may hinder its use in the diagnosis of polyps or
      tumors in the small bowel. In the next years it will be exciting to see whether
      capsule endoscopy will finally reach the clinical significance we expect at the
      moment. Possibly, the diagnostic algorithm for obscure gastrointestinal bleeding
      has to be changed in the future due to the abandonment of less effective
      procedures.

PMID- 12070455
TI  - Stress response proteins and renal ischemia.
AB  - Acute renal failure is a frequent clinical entity with an increasing incidence
      and an unacceptably high mortality, yet there is no specific treatment. The
      induction of stress response (heat shock) proteins (HSPs) is a highly conserved
      response that protects many cell types from diverse physiological and
      environmental stressors. Diverse HSP families of different sizes function as
      molecular chaperones that facilitate the folding of enzymes and other proteins
      into the functional conformation. After injury, HSPs are believed to facilitate
      the restoration of normal function by assisting in the refolding of denatured
      proteins and degradation of irreparably damaged proteins and toxic metabolites,
      limitation of aggregation of damaged peptides and aiding the appropriate folding
      of newly synthesized essential polypeptides. We have recently demonstrated
      protection from the functional deficits and histologic evidence of experimental
      ischemic renal injury with heat stress 6 hours but not 48 hours prior to the
      ischemic insult. Limitation of the induction of HSPs (either with a short period
      of hyperthermia or pharmacologically) attenuated the protection observed. Other
      investigators have demonstrated a correlation between the levels of HSP 25 and
      renal ischemic preconditioning in the mouse. Several pharmacologic agents have
      been shown to increase HSP expression. Enhancement of these endogenous protective
      mechanisms has potential benefit in human disease.

PMID- 12070454
TI  - Cardiovascular risk reduction in renal transplantation. Strategies for success.
AB  - One of the aims of transplantation is to restore the potential for a full life to
      individuals with ESRD. To obtain this strategies that allow better and longer
      allograft function and a reduction in adverse events that lead to premature death
      are required. To this end, the recommendations below showed reduce cardiovascular
      disease and help present and future transplant recipients live a full life.
      Focusing on traditional risk factors (hypertension, hyperlipidemia,
      discontinuation of smoking, and prevention and treatment of diabetes mellitus) in
      patients at risk and striving for the recommended targets will have the greatest
      clinical benefit. These strategies should begin in the pre-dialysis and dialysis
      phases in order to reduce the cumulative burden of disease. Failing this, early
      and hopefully pre-emptive transplantation should be the goal.

PMID- 12070456
TI  - Anti-viral drugs in continuous ambulatory peritoneal dialysis (CAPD).
AB  - The prevalence of HIV-positive subjects in dialysis (hemodialysis and peritoneal
      dialysis) population varies from 0.13 to 0.36% in italian and french studies,
      respectively. Most drugs used in HIV therapy are primarily excreted by the
      kidney. In patients with renal insufficiency, careful dosage adjustment is
      mandatory to optimize drug exposure and reduce the risk for adverse events. We
      review the impact of peritoneal dialysis on the pharmacokinetics of antiviral
      drugs, and discuss on the dosage recommendations needed to achieve efficacy and
      avoid toxicity in patients with end-stage renal disease undergoing continuous
      ambulatory peritoneal dialysis (CAPD).

PMID- 12070458
TI  - [Immunotherapy in the management of metastatic renal carcinoma].
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a relatively rare tumor representing 2
      3% of all neoplasias. Approximately 30% of patients diagnosed as having RCC
      present metastases: mean survival ranges between 6 and 10 months, whilst 10-20%
      present a 2-year survival rate. Treatment of patients with metastatic RCC is a
      difficult challenge. Hormones and chemotherapy, either alone or associated with
      surgical resection of the primary lesion have been used. In our experience, IL-2
      + IFN-a has been shown to be an encouraging form of treatment. METHODS: During
      the period between October 1997 and December 1999, 5 patients (3 males, 2
      females), mean age 52.5 years, with metastatic RCC, came to our attention. TC
      revealed a circumscribed area the margins of which were not well defined, in a
      mid-renal localization, positive inter aorta caval and obturator lymph nodes, but
      no lung, brain or hepatic involvement. Patients were submitted to nephrectomy and
      lymphadenectomy followed later by immunotherapy with IFN-alpha (3 Mil twice a
      week) + low dose IL-2 (1 Mil/m2/12 h): treatment was given for 4 consecutive
      weeks and then repeated every 3 weeks for 1 year. RESULTS: At 30 months' follow
      up all patients showed regression of the disease (100% of cases) and in none of
      the cases there was evidence of metastases. Only one patient (20%) presented side
      effects (nausea, vomiting, slight rise in temperature) all of which disappeared
      at the end of the first week of treatment. CONCLUSIONS: These results, even if on
      a limited number of patients and for a limited follow-up period, show that in
      some patients with metastatic renal cell carcinoma, treatment with IL-2 and IFN-a
      following nephrectomy and lymphadenectomy should be considered the therapy of
      choice.

PMID- 12070457
TI  - [Treatment of complications in hypospadias surgery: modern advancement].
AB  - BACKGROUND: With today's improved surgical techniques, complications in
      hypospadias surgery are seen less often, especially in distal form (1-5%).
      However, in proximal or complex hypospadias complications rate varied between 15
      and 57%. Corrective surgery is mandatory in maior complications (urethrocutaneous
      fistulas, persistent chorde, urethral strictures, superficial skin separation).
      The search for the innovative surgical procedures and the optimal urethral
      substitute continues because each tissue has its particular shortcomings and
      disadvantages. METHODS: At our hospital complications occurred in 25 ( 15%) of
      177 patients who underwent primary hypospadias repair between 1994 and 1998. 9
      patients required further surgery to repair the complications of previous
      hypospadias operations performed at other institutions. When local epithelial
      tissue was not available, different surgical procedures were performed, using
      bladder or buccal mucosa graft and free or vascularized tunica vaginalis flaps.
      RESULTS: Follow up ranged from 3 to 6 years: the cosmetic and functional results
      were excellent. Small fistulas occurred in 3 patients and were corrected
      successfully in a subsequent surgical procedure using a tunica vaginalis wrap.
      CONCLUSIONS: The concept of using tunica vaginalis in urethral reconstruction
      represent a recent innovation. This tissue is a valid alternative in cases of
      multiple failed repairs.

PMID- 12070459
TI  - [Pregnancy after kidney transplantation. Review of the international literature
      and presentation of personal case reports].
AB  - BACKGROUND: Advances in surgical techniques and immunosuppression have improved
      the results in organ transplantation. The quality of life in these patients is
      good in the most of cases and pregnancy, which means for them to resume a normal
      life, isn't an exceptional event, specially for kidney transplant recipients.
      METHODS: Retrospective data regarding pregnancies observed at the Dept. of
      Nephrology and Dialysis of the S. Giovanni Battista Hospital in Turin, have been
      collected to value the pregnancy frequency and outcome (complications,
      miscarriage, therapeutic abortion), the mother follow-up as a function of
      transplant rejection risk, the newborn conditions, their hematological and
      immunological situation, and the children follow-up. RESULTS: This study includes
      9 pregnancy (6 at term and 3 abortions), observed since 1987 in 6 kidney
      transplant recipients. Congenital malformations or immunological diseases have
      not been observed; according to the literature, there was a high frequency of
      preterm delivery and intrauterine grow retardation. Complications during
      pregnancy were observed in 5 cases (83.3%). CONCLUSIONS: The study confirms that
      kidney transplant recipients can carry a pregnancy through and give birth to
      healthy infants, but these pregnancies are to be regarded as being at high risk
      and require a multi-disciplinary approach.

PMID- 12070460
TI  - Iatrogenic bladder stone formation on absorbable suture 3-years after radical
      prostatectomy.
AB  - Vesical calculi formation on absorbable sutures is rare. The case of a 68-year
      old white man, who had formed a large bladder stone on absorbable suture 3 years
      after radical prostatectomy, is reported. Endoscopic lithotripsy of the bladder
      calculi was performed and the suture was removed.

PMID- 12070461
TI  - [Penile metastasis from bladder cancer. A case report].
AB  - Penile metastases from bladder cancer are unusual. A case of a man, 50 years old,
      with undifferentiated bladder carcinoma submitted to radical cystoprostatectomy
      and ileal conduit is presented. Twelve months after the primary diagnosis the
      patient presented metastases of the penis.

PMID- 12070462
TI  - Retroperitoneal lipoma. Unusual presentation with detrusor instability.
AB  - Retroperitoneal lipomas are a heterogeneous group of mesenchymal tumors. They are
      usually large and occur most frequently in the retroperitoneal, perineal and
      pelvic regions. Lipomas grow slowly surrounding the retroperitoneal and pelvic
      organs, with a displacement of bowel and vascular axis. A case of a 61-year-old
      male patient which referred urinary frequency, urgency and nocturia is presented.
      Urodynamics evidenced a detrusor instability in a low capacity bladder. CT scan
      demonstrated a bladder dome compression due to a huge retroperitoneal mass
      extending from the right hepatic lobe to the hypogastric region and the right
      thigh. Surgical complete resection was performed: histology demonstrated a lipoma
      with areas of well differentiated myxoid degeneration. After surgery the
      irritative urinary symptoms disappeared. This is the first case described in
      literature of detrusor instability due to bladder compression by retroperitoneal
      lipoma.

PMID- 12070463
TI  - [Hydatid cyst of the kidney. Case report].
AB  - The authors present a case of echinococcosis of the kidney that is interesting
      because of the uncommon site of localization; they illustrate their diagnostic
      and therapeutic approach to surgical and pharmacological management of the
      infection. Epidemiologically, hydatid cysts localized in the kidney occur far
      less often in northern Italy compared with the central-southern areas and the
      islands. However, echinococcosis should be suspected whenever symptoms include
      lumbar pain or swelling. Echography will reveal characteristic capsule and
      daughter cysts, while radiographic studies will often show a rim of calcification
      on the outline of the kidney. This information should be considered in
      conjunction with serologic tests (IgG-specific titers). If results to these tests
      are negative, abdominal computed tomography scans with contrast medium may be
      useful in demonstrating more details to establish diagnosis. Conservative
      (pericystectomy) or radical (nephrectomy) surgery is usually effective in curing
      the patient. Pharmacological therapy with albendazole can be a useful support in
      association with surgery or as an alternative single therapy in patients with
      other medical problems or spontaneous fistula formation that preclude surgery.

PMID- 12070464
TI  - [Daily short dialysis. First results in a group of patients in home dialysis
      training].
AB  - The preliminary data of a small group of voluntary patients in daily short
      dialysis according to Buoncristiani are reported. After only one month of therapy
      an increase of haemoglobin and of haematocrit was obtained so that it was
      possible to reduce the EPO dose. The arterial pressure was better controlled with
      a smaller dose of antihypertensive drugs, facilitated in one case by a marked
      reduction of the body weight. The improvement in well-being and libido has been
      better than expected. The good results achieved encourage to go on with this
      experience, reported in the literature as an advantageous method both from the
      theoretic and clinical point of view, despite some difficulties that have still
      to be minimised.

PMID- 12070465
TI  - [Treatment of post kidney transplantation erythrocytosis (PTE) with ACE
      inhibitors].
AB  - BACKGROUND: Post kidney transplantation erythrocytosis is a frequent complication
      in male subjects. In our experience, it occurs in approximately 20% of transplant
      patients receiving cyclosporine immunosuppression therapy. METHODS: Twenty-two
      patients with post kidney transplantation erythrocytosis were treated using ACE
      inhibitors (lisinopril) at a dose of 2-5-5 mg/day for a mean period of 15 months.
      Owing to the onset of collateral effects, 27% of these patients requested the
      conversion of ACE into angiotensin II receptor antagonists (AII). Twenty out of
      22 patients were male (90%). RESULTS: Treatment resulted in a 15% reduction of
      hematocrit values compared to basal levels, which remained stable over time. No
      collateral effects were recorded, either for the kidneys or in terms of
      hypotension. CONCLUSIONS: ACE-inhibitors (lisinopril) or alternatively the use of
      angiotensin II receptor antagonists, like Losartan, at low doses, is an effective
      and safe treatment for patients developing post-transplantation erythrocytosis
      (PTE).

PMID- 12070466
TI  - [Maxillary sinus lift in conjunction with endosseous implants. A long-term follow
      up scintigraphic study].
AB  - BACKGROUND: To evaluate the efficacy of bone scintigraphy in the long-term follow
      up of maxillary sinus lift by a mixture of bovine hydroxyapatite and autologous
      fibrin glue in conjunction with the insertion of endosseous implants. METHODS: A
      three-years follow-up study involved 18 surgical interventions performed on 14
      edentulous patients (4 F; 10 M; mean age 49 yrs) suffering from mono or bilateral
      severe distal maxillary resorbtion. The bone scintigraphy of the skull was
      performed before, 1-18 months and 36 months post-intervention. Perimplant bone
      metabolism was quantified by a parameter called M/V index, used to statistically
      compare normal, atrophic and regenerate maxillary bone. Conventional
      radiographies were performed every six months; CT dental-scan 12 months post
      intervention. RESULTS: Bone perimplant metabolism showed top values 1-4 months
      post-intervention (M/V%2-2.2); then it showed a decreasing trend and the lowest
      values 36 months post-intervention. M/V index in the atrophic (0.6) and normal
      (0.7) maxillary bone was lower (p<0.05) than in the new formed one (0.8).
      Radiologically a good integration of the dental implants was found in the new
      formed bone; the CT-measured average maxillary height was equal to 1 cm.
      CONCLUSIONS: The combination of several bioactive components in the mixture used
      didn't allow to detect the bone inductive role of the single products. Instead,
      quantitative bone scintigraphy confirmed its efficacy to gain important data
      about natural history of the endosseous implants and the value of the surgical
      technique. In particular we observed complete osseous integration of dental
      implants inserted in the mix of bovine hydroxyapatite and autologous fibrin glue
      is achieved 2-3 years after the intervention. After this period, possible
      pathological aspects suggest an early treatment to save the implants.

PMID- 12070467
TI  - [Stabilimetry and cranio-cervico-mandibular disorders].
AB  - BACKGROUND: Cranio-cervico-mandibular disorders can cause disturbances in
      posture. Stabilimetry measures spatio-temporal variations in the center of body
      pressure and evaluates the mechanisms of maintenance of balance. The study used a
      stabilimetric platform to evaluate posture changes in patients with cranio
      cervico-mandibular disorders before and after treatment for malocclusion.
      METHODS: Between February 1998 and December 2000, 60 patients with cranio-cervico
      mandibular disorders were recruited from the Dentistry Clinic of the University
      of Sassari. Each patient underwent two stabilimetric examinations (closed mouth
      with cotton wads inserted between the dental arches). The tests were conducted on
      a stabilimetric platform. Measurement of body posture load and sway were analyzed
      with a specific software program that correlated the vestibular, somatosensory
      and visual systems, and determined the role of each in postural control. RESULTS:
      The stabilimetric analysis showed that the adoption of the plaque allowed
      rebalance of the postural system, without affecting the visual system. After
      treatment, 64% of patients experienced remission of pain symptoms with orthotic
      therapy. CONCLUSIONS: The relationship between malocclusion and posture should be
      seen from a holistic standpoint in other to gain a global therapeutic outcome.

PMID- 12070468
TI  - Prevention and treatment of chemo- and radiotherapy-induced oral mucositis.
AB  - The administration of many chemo-radiotherapy regimens in patients with cancer
      may be complicated by toxicities that limit the clinicians' abilities to deliver
      the most effective doses of active agents. Oral mucositis is a major dose
      limiting toxic effect and the most important cause of morbidity in patients
      undergoing chemo-radiotherapy for head and neck cancers, in patients undergoing
      bone marrow transplantation and those receiving certain chemotherapeutic agents
      for a variety of human malignancies. The intent of this paper is to review
      preventive strategies and treatment approaches for patients with established oral
      mucositis. Many agents of differing mechanisms of action have been used in the
      prevention and treatment of oral mucositis induced by anticancer therapies.
      Currently, no intervention is completely successful at preventing or treating
      oral mucositis. The several solutions, drugs and methods used and studied in the
      prophylaxis and therapy of chemotherapy or radiotherapy-induced oral mucositis
      reflects the need of new, more efficient tools in the management of this
      complication. Current studies and our increasing understanding of the etiology
      and pathogenesis of oral mucositis will lead to new approaches to the management
      and improved quality of life for these patients.

PMID- 12070469
TI  - [Biofilms of the oral cavity. Formation, development and involvement in the onset
      of diseases related to bacterial plaque increase].
AB  - Biofilm is defined as a community of bacteria intimately associated with each
      other and included within an exopolymer matrix: this biological unit exhibits its
      own properties, quite different in comparison with those showed by the single
      species in planktonic form. The oral cavity appears as an open ecosystem, with a
      dynamic balance between the entrance of microrganisms, colonisation modalities
      and host defences aimed to their removal: to avoid elimination, bacteria need to
      adhere to either hard dental surfaces or epithelial surfaces. The oral biofilm
      formation and development, and the inside selection of specific microrganisms
      have been correlated with the most common oral pathologies, such as dental
      caries, periodontal disease and peri-implantitis. Many of these bacteria are
      usual saprophytes of the oral environment, that, in particular situations, can
      overcome and express their virulence factors: to better understand the mechanisms
      of these pathologies it's necessary to know the complex interactions between all
      the bacterial species inside the biofilm and host tissues and responses. The
      present paper is a review of the most significant studies on the biofilm
      development modalities, their correlations with either health or illness of the
      oral cavity, the bacterial co-aggregation strategies and the biofilm response to
      antimicrobial agents.

PMID- 12070470
TI  - [Histological and ultrastructural characteristics of jaw-closing muscles. A
      review].
AB  - The aim of this work is giving, through a wide literature review, a detailed
      analysis of the histological and ultrastructural characteristics that distinguish
      masseter and temporal muscles from the other skeletal muscles. Furthermore we'll
      explain the functional meanings of these differences. We developed the following
      points: fibre type composition and relative frequency of the various fibre types,
      fibre size, myosin composition, capillarization and age-related changes. With
      standard staining method for the myofibrillar ATPase, besides the two main fibre
      types, I and II, in the masticatory muscles a moderate share of IM fibres with
      intermediate stainability, which usually don't appear in adult skeletal muscles,
      are shown. The relative frequency of the various fibre types is also peculiar,
      with a prevalence of type I fibres in almost every portion of the masseter and
      temporal muscles, which therefore are functionally slow muscles. Another unusual
      characteristic is also the mean diameter of type I fibres, that are commonly
      larger than type II fibres. This finding suggests that masticatory muscles are
      adapted to carry out specially prolonged and fatiguing tasks. The findings about
      contractile protein patterns and the changes in myosin heavy chain composition
      during ageing are also relevant. The deep differences between jaw-closing and
      limb and trunk muscles are reviewed on the basis of their special functional
      activities.

PMID- 12070471
TI  - [Biology of periodontal regeneration: a review and a hypothesis for future
      researches].
AB  - Since the end of the seventies several studies have been carried out about the
      possibility of regeneration of periodontal osseous defects. The results of such
      researches supported by histological tests allowed to establish which surgical
      techniques could yield periodontal regeneration in a predictable way. In spite of
      a quite large diffusion of these sugical techniques in the treatment of
      periodontal osseous defects, some biological aspects of periodontal regeneration
      are still unknown. The most important among them is the origin and the
      differentiation pathway of the synthetic cells that shall provide for the
      reconstruction of the deep periodontium. Particularly, the phenotypic pattern and
      the origin of cementoblasts are not clear. Our researches focused on pericytes, a
      mesenchyma-derived cell population with remarkable differentiation capacities
      which have a microvascular location. We considered the hypothesis that pericytes
      could play an important role in regeneration of the alveolar bone, of the
      cementum and of the periodontal ligament. Should pericytes be actually the
      precursors of osteoblatsts, fibroblasts and cementoblasts involved in periodontal
      regeneration, new therapies, such as cultivated cells reimplantation or the
      targeted use of growth factors could be feasible. Future researches shall verify
      these observations.

PMID- 12070472
TI  - [Necrotizing sialometaplasia. A clinical case].
AB  - In the present study, a rare pathology, described for the first time in 1973 has
      been examined. In particular, the nosologic picture of the disease, the
      etiopathogenetic hypotheses, symptoms and diagnostic procedures reported in the
      literature have been analysed. The case of a man showing a neo-formation, in the
      midline region of the hard palate, that appeared only following ingestion of very
      hot food is examined. The surgical procedure is reported and discussed in detail,
      and the histopathological analysis showing a necrotizing sialometaplasia is
      reported. Prognosis and possible therapeutic approaches are also discussed.
      Finally, the attention has been focused on the histological similitary between
      this pathology and squamous cell carcinoma or epidermoid carcinomas.

PMID- 12070473
TI  - Unusual surgical approach in a bilateral case of mandibular buccal infected cyst.
AB  - In the new edition of WHO's "Histological typing of odontogenic tumors", the
      mandibular infected buccal cyst, that is associated with the lower first or
      second permanent molars, is considered a paradental cyst as well as the
      inflammatory collateral cyst, which is usually related to the lower third molar.
      The lesion occurs on the buccal and lateral aspects of the roots of mandibular
      molars with vital pulp, at the eruption time, in children aged between 6 and 10
      years. The inflammation is always present in these cysts and may have an
      important role in their pathogenesis because it stimulates hyperplasia and cystic
      change of the reduced enamel epithelium or the epithelial cell rests of Malassez.
      The authors report the case of a 7-year-old girl, in whom both first mandibular
      molars were affected by an infected buccal cyst. A different surgical approach
      was performed with marsupialization on the left side and cystectomy on the right
      side. The case reported here seems to be interesting because it is the second
      well documented case of bilateral mandibular infected cyst associated with
      unerupted molars and because the adopted treatment differs from the therapeutical
      approach suggested in the literature. A 6-year follow-up demonstrates a correct
      dental and bone evolution on both mandibular molar sides.

PMID- 12070475
TI  - Enhancing STD/HIV prevention among adolescents: the importance of parenteral
      monitoring.
AB  - The risk of acquiring sexually transmitted diseases (STDs) and HIV infection is
      one of the most significant and immediate risks to the health and well being of
      adolescents. One promising strategy to protect adolescents from STD/HIV infection
      is to promote parental monitoring. In this article, we first review selected
      observational studies that provide evidence supporting the value of parental
      monitoring in reducing adolescents' risk of STD/HIV acquisition. Subsequently, we
      discuss the potential implications of the research in regards to clinic- and
      community-based STD/HIV prevention programs for adolescents.

PMID- 12070474
TI  - [In vivo evaluation of carbon fiber posts].
AB  - BACKGROUND: The use of carbon fiber posts allows morpho-functional restoration of
      endodontically treated teeth with an assembly of materials of a modulus of
      elasticity similar to that of dentin. The study clinically evaluated the
      percentage of survival of dental elements treated and reconstructed with
      endocanal carbon fiber posts. METHODS: At the Dentistry Clinic of the University
      of Sassari 60 dental elements were selected from 46 subjects. The teeth, which
      had been treated endodontically with success for at least six months, were
      classified by parameters taken from the international literature and
      reconstructed using Tech 2000 carbon fiber posts and adhesive resinous systems
      recommended by the post manufacturer. RESULTS: The success rate was 98.4%. Almost
      half (49%) of the samples were single-rooted elements, 37.4% of the posts were
      1.2 mm in diameter; in 78.3% the opposing contact was with a natural tooth; 100%
      of the elements had a type A dental structure. CONCLUSIONS: Third generation
      posts are a valid alternative to metallic posts and improve the prognosis of the
      treated element. The carbon fiber posts fixed with the composite, forming a
      single unit with the dental element, thus improving mid-term RESULTS. The
      technique is easy to use under clinical conditions and can be performed in a
      single session. So far, the method has provided promising clinical results, as
      this study demonstrated.

PMID- 12070476
TI  - Diet quality, nutrient intake, weight status, and feeding environments of girls
      meeting or exceeding the American Academy of Pediatrics recommendations for total
      dietary fat.
AB  - The American Academy of Pediatrics (AAP) recommends that children consume no more
      than 30% but no less than 20% of energy as dietary fat intake, and this
      recommendation is accompanied by suggestions that fat calories should be replaced
      by eating more grain products, fruits, vegetables, low fat dairy products, beans,
      lean meat, poultry, fish, and other protein rich foods. In comparing diets of
      girls meeting this AAP recommendation with girls who consumed diets higher in
      fat, we noted that girls meeting recommendations had diets that came closer to
      meeting other dietary recommendations for several food groups and had higher
      intake of several key micronutrients. Dietary fat was also associated with body
      fat and weight status. Children's fat intake was also related to mothers' dietary
      fat intake, and nutrient intake patterns were similar for mothers and daughters.
      Finally, mothers of girls consuming higher fat diets reported using more
      restriction and pressure to eat in feeding their daughters. These findings
      provide additional support for the AAP recommendation to limit total dietary fat.
      Findings reveal that mothers' use of controlling feeding practices are not
      effective in fostering healthier diets among children, and that mothers' own
      eating may be more influential than their attempts to control children's intake.

PMID- 12070477
TI  - Angiopathy in children with diabetes.
AB  - Diabetic angiopathy includes those complications associated with chronic
      hyperglycaemia. The major long-term complications of diabetes can be categorized
      into two classes: macrovascular (i.e., cardiovascular complications) and
      microvascular (i.e., nephropathy, retinopathy, and neuropathy). Clinically
      evident diabetic vascular disease is rare in children and adolescents with type 1
      diabetes mellitus: however, the permanent threat of severe vascular organ disease
      within one or two decades, of early invalidity and limited life expectancy
      following long-term poor metabolic regulation (which is known to the health
      professional but only incompletely sensed by the young patient), forces the
      paediatrician to try to reach from the start the aim of normoglycaemia instead of
      merely somewhat reduced hyperglycaemia, normal lipid and amino acid patterns and
      near normal fluctuations of all metabolic parameters. With our present means of
      intervention, this goal is achieved only temporarily, if at all, necessitating
      immense permanent efforts by the patient and his or her family, including a
      greater responsibility (compared to that of his/her peers) for his/her everyday
      lifestyle. In this review natural history, risk factors and screening of diabetic
      microvascular and macrovascular complications will be described, with particular
      emphasis to the aspects of these complications in childhood and adolescence.
      Pediatric diabetologists, other health professionals and families of children
      must be aware of the risk of diabetic angiopathy (a Damocle's sword on the head
      of patients with diabetes) and try to do their best for preventing these
      complications.

PMID- 12070478
TI  - [Protein quality and quantity in infant formulas. A critical look].
AB  - The ideal quantity and quality of dietary proteins in milk formulas employed for
      infant nutrition is still a matter of controversy and debate. During the last
      years, there has been a tendency to lower the protein content in response to new
      estimations of protein requirements based on protein intakes and growth rates of
      breastfed infants. In most infant formulas the protein content is in the range of
      1.4-1.8 g/100 ml. The lower limit of this range appears to be adequate for the
      growth and metabolic needs of the healthy infant. The safety of a further
      reduction of this limit to 1.2 g/100 ml (~1.8 g/100 kcal), which has been
      recently proposed, needs additional scrutiny and observation. In addition, the
      real benefits of this choice have still to be proven. Adjustments for protein
      digestibility and quality have recently been introduced. The removal from the
      whey protein fraction of the glycomacropeptide (GMP), with a consequent reduction
      of excessive threonine intakes, is a novel approach and a further step in the
      development of infant formulas closer to the model of hu-man milk.

PMID- 12070479
TI  - [From informed to shared: the developing process of consent].
AB  - Based on the respect of the four well known ethical principles "autonomy, non
      maleficence, beneficence and justice", of clinical cognitive psychology, social
      psychology and bioethics, and in the light of moral values, we wish to comment
      the clinical problems involving informed consent for diagnostic procedures,
      treatment and research in pediatrics. Studies of the issues in attitudes and
      shared consent in the clinical management involving children, their parents and
      the therapeutic team are still limited. Our suggestion is to manage the process
      of informed consent as a negotiated "shared consent" originated from the
      cognitive social representation theory, and taking into consideration the
      evolutive characteristics of the cognitive processes in children and adolescents,
      the ego defence mechanisms, the coping behaviour activated in the relationship
      among the pediatric patient, his/her family and the physicians. Many parents told
      us that the informed consent process is helpful though often confusing.
      Satisfaction was not related to ethnicity or education level. They found
      discussions more helpful than the consent documents. The more difficult process
      concerned their understanding of the concept of randomisation and the request of
      their consent to this procedure. The model we suggest has also the aim to give
      adequate and honest informations to children and adolescents through a continuous
      dialogue with the physician, until this become a routine part of their life in
      hospital care, to avoid confusion, to satisfy any request and curiosity, to be
      honest and helpful with any answer. We strongly believe that medical students,
      and in particular pediatricians, must be trained on "communication" and that they
      need to acquire, in addition to their medical capability, a good knowledge on
      this topic, including ethics and relational aspects. In our opinion,
      pediatricians must become expert also in the following topics: "Problem-related
      Learning", "The Family System Health Model", "The Theory of Social
      Representations", "Gadamerian Hermeneutics", and "The Communicative Skills".

PMID- 12070480
TI  - Intermittent treatment with high dose nebulized beclomethasone for recurrent
      wheezing in infants due to upper respiratory tract infection.
AB  - BACKGROUND: To investigate if high dose inhaled beclomethasone dipropionate
      started early after upper respiratory tract infection (URTI) could reduce
      recurrent wheezing in infants. METHODS: Twenty-six ambulatory infants, 7-12
      months of age, with recurrent wheezing during upper respiratory tract infection
      participated. All experienced at least three wheezing attacks. Those with
      underlying lung or systemic disease were excluded. Infants were divided into two
      groups in an open unblinded manner, until 13 patients had been recruited for each
      group. The groups were similar in risk factors for recurrent wheezing. Four
      treatment periods of 5 days were planned for group 1. The dose regimen was
      nebulized beclomethasone 400 mg by mask tid for 5 days. Treatment was started at
      the very first sign of URTI prior to any sign of wheezing. Group 2 did not
      receive any preventive treatment and constituted the control group. Symptoms
      scores were recorded. The number of emergency room visits, hospital admissions
      and short courses with oral steroids was also noted. RESULTS: Twelve infants
      completed 48 treatment periods. Five visited the emergency room, only one during
      beclomethasone therapy. Six received oral steroids, two receiving beclomethasone.
      No patient was admitted to the hospital. Symptom scores were significantly lower
      during beclomethasone treatment (p<0.05). No apparent adverse events were
      reported. CONCLUSIONS: The infant with recurrent wheezing during URTI is a
      therapeutic challenge. Most of these infants have prodromal symptoms for about 24
      hours before wheezing starts. In the present study we observed favorable results,
      decrease in the number the child wheezed and the number of acute attacks, when
      high dose inhaled beclomethasone is administered during this critical time.

PMID- 12070481
TI  - Birthweight centiles in preterm infants. A new approach.
AB  - BACKGROUND: To analyze the birth weight of preterm infants developing a new
      methodology in order to efficiently collect data. METHODS: We have analyzed the
      birthweight of 2,482 preterm babies with a gestational age between 24 and 36
      weeks admitted to a Neonatal Intensive Care Unit from 1991 to 1998. The
      gestational age was determined from obstetric data. No selections were performed
      at the earlier stages of the study by excluding newborns with congenital defects,
      sepsis, intrauterine growth retardation or obstetric pathologies. More selective
      criteria were applied at the final stage by using statistical tests. The
      anomalous and extreme weights for every gestational age were identified with Box
      and Whisker graphs. The clinical records of these cases were analyzed and their
      characteristics described but these weights were excluded from the calculation of
      the percentiles. For each gestational age we evaluated if the weight distribution
      was assimilable to normal distribution by calculating the kurtosis, asymmetry by
      applying the Kolmogorov-Smirnov and Shapiro test. RESULTS: In the majority of
      cases we found a normal weight distribution. CONCLUSIONS: The proposed
      methodology seems useful in making data collection for preterm centiles
      calculation simpler. A study of the clinical characteristics of the SGA and LGA
      identified with the normal procedure or with the proposed method might be useful
      in validating our approach to the definition of the percentiles.

PMID- 12070482
TI  - [Influence of diet on lipoprotein profile in familial combined hyperlipidemia
      affected children].
AB  - BACKGROUND: Familial Combined Hyperlipidemia is an inherited disorder affecting
      cholesterol and triglycerides metabolism, well known myocardial infarction risk
      factors. The FCHL clinical presentation is usually silent until the third decade
      although children can be affected, and the more recent opinion is that precocious
      diagnosis is mandatory in preventing complications. Aim of this study is to
      examine the effectiveness of the diet therapy (Step-One-Diet) in a group of 13
      children affected by Familial Combined Hyperlipidemia. METHODS: The patients have
      been submitted to a normocaloric diet, 30% fat of the total caloric daily intake
      according with the Dietary Intervention Study in Children (Step-One-Diet). The
      patients then have been submitted to a two year-follow-up and lipoprotein levels
      (total cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B),
      nutritional status (macro- and micro-nutrients) as well as anthropometric data
      (height, weight, BMI) have been monitored. RESULTS: Results showed a 10% total
      cholesterol and 30% triglycerides decrease, Iron and Calcium intake show
      increased levels approaching to the normal ones after controlled diet, while
      cholesterol intake was correct on both regimen. The growth parameters show a
      decrease in weight only in two obese and two overweight patients. CONCLUSIONS:
      The present study confirmed the effectiveness and safety of the Step-One-Diet in
      children patients, allowing triglycerides normalization in 60% of the patients,
      and a 10% cholesterol decrease, in agreement with the complex genetic inheritance
      of the disease.

PMID- 12070483
TI  - Dog bites in children less than fourteen years old in Turin.
AB  - BACKGROUND: The purpose of this study was to describe the epidemiology of
      injuries caused by dog bites treated in the emergency department of OIRM from
      January 1, 1997 to December 31, 2000. METHODS: Data on dog's attacks were
      obtained from declaration forms filled in the emergency department. RESULTS: 253
      children were observed: 145 boys and 118 girls. The mean age was 6.4 years. The
      peak incidence was in children aged 3 to 8 years old. Fifty-six children (22.31%)
      required admission to the hospital. Thirty-five were younger than 5 years.
      Injuries to the face (29.48%), hands (14.55%), legs (9.33%) were more common. The
      prognosis was 5 (18.97%), 7 (21.74%) and 10 (16.6%) days. Twenty-five children
      had prognosis over fifteen days (9.88%). Children aged 5 or younger presented
      most face and hand lesions while children aged 6 to 14 years had most hand, legs
      and arms injuries. Tetanus and rabies prophylaxis were administered only in 4 and
      2 cases respectively, while immunoglobulin anti tetanus were administered in 5
      children. The great number of attacks occurred during the summer months, with a
      peak in June and July. CONCLUSIONS: More attention should be paid to the
      prevention of dog bites. Pediatricians should advice parents about the risks of
      interactions with dogs.

PMID- 12070484
TI  - [Loeffler syndrome and Mycoplasma pneumonitis. A case report].
AB  - We describe a clinical case of Loeffler syndrome occurred in a famale aged 13
      years. This syndrome is characterized by fleeting pulmonary infiltrates and blood
      eosinophilia until 70%. Patients usually are only mildly ill or asymptomatic and
      recovery occurs from few days to some months. Principle causes are: a) mycetes as
      Aspergillus; b) helmints as Toxocara, Ancylostoma, Trichinella, Ascaris,
      Strongyloides, Schistosoma; c) chemical agents such as penicillin, para
      aminosalycilic acid, hydralazine, nitrofurantoine, chlorpropamide. This girl came
      to our observation in good general conditions with murmur reduction on the thorax
      left side, marked peripheral eosinophilia (E 55% of 6100 white blood cell), right
      pulmonary infiltrate on RX and CT scan. One month before she had fever, treated
      with amoxycillin and clavulanic acid. Mantoux, Prick tests for main inhalant
      allergenes, ACE, repeated stools and seric investigations for parasites, mycetes
      and organisms, were negative except for IgM anti-Myco-plasma antibodies.
      Broncholavage showed marked eosinophilia. Smear didn't show any blast. The girl
      recovered in about 40 days (E 4.1% of 8500 WBC, RX negative). Our hypotesis is a
      causative role of amoxycillin in inducing the syndrome, even if this is a rare
      event, with an overlapping of a Mycoplasma infection.

PMID- 12070485
TI  - The child's awareness of the concept of mental disease. A case study.
AB  - In international literature not many papers discuss the comprehension of the
      mental disease concept by children and their ability to understand its behavioral
      and ethical consequences. A knowledge of this domain could be very important for
      health professionals and practitioners who have to cope with children abused by
      adult relatives with psychiatric illnesses. The case study of an 8 year-old girl
      describes a brief child training, projected to facilitate the recovery of the
      child mother relationship, through the child's comprehension of the concept of
      mental disease. The girl was initially assessed in a child psychiatric clinic
      after a period of hospitalization caused by a severe physical aggression
      committed by the mother during an acute schizophrenic episode (an attempt of
      homicide and suicide). Post Traumatic Stress Disorder (PTSD) and other
      psychopathologies were absent in the child. The training project included: 1) the
      achievement of a confidential relationship between the girl and the doctor, 2)
      the child's comprehension of the general concept of illness, 3) the child's
      comprehension of the concept of mental illness and the absence of responsibility
      relative to the bizarre and aggressive behavior of the psychiatric patient. After
      2 months of child training, the girl showed a partial but sufficient
      comprehension of the concept of mental illness. Hence, the girl successfully
      restored her relationship with the mother, without developing any
      psychopathological effects. This result was confirmed after one year.

PMID- 12070486
TI  - Guillain-Barre syndrome after varicella zoster virus infections. A case report.
AB  - The case of a 13 year-old patient affected by Guillain-Barre syndrome developed
      after varicella zoster virus infection is reported. Cerebrospinal fluid
      examination and motor and sensory conduction velocity were consistent with GBS.
      Antibodies against gangliosides GM1 were present; it is likely that some of these
      may play an important role in the pathogenesis of syndrome after varicella
      infection. The therapy was carried out with increasing high-doses of
      immunoglobulins, with full clinical recovery.

PMID- 12070487
TI  - Thyroid nodules.

PMID- 12070488
TI  - Hypoparathyroidism and pseudohypoparathyroidism.

PMID- 12070489
TI  - Hypothyroidism.

PMID- 12070490
TI  - Outcome of rotator cuff repair.
AB  - From 710 consecutive open rotator cuff repairs by a single surgeon, the results
      of 667 were available for detailed analysis. Patient-assessed outcomes and the
      ability to perform specific activities of daily living, employment, and
      recreation were correlated with independent nonstructural variables including
      age, sex, workers' compensation status, and revision surgery status. The study
      shows that patient self-assessment of satisfaction is very high, with 87.5% of
      all respondents pleased overall. Detailed assessment is provided of certain
      subgroups that are more likely to report worse results after surgery. These
      include patients on workers' compensation, those undergoing revision surgery, and
      those younger than 55 years of age. Information presented here may be useful
      during preoperative counseling for rotator cuff repairs, to ensure realistic
      patient expectations.

PMID- 12070491
TI  - Structural factors affecting the outcome of rotator cuff repair.
AB  - A retrospective review of 667 rotator cuff tears analyzed structural factors that
      might influence outcome. Tear size was not found to be an indicator of likely
      patient satisfaction, and concomitant rupture of the biceps tendon did not
      prejudice the outcome. In this first reported study of the influences of
      delamination disease and the surgical manner in which it is treated, it was found
      that at least when treated by interlaminar curettage before repair, cuff
      delamination did not appear to prejudice patient satisfaction. The study also
      found that tendon-to-tendon and tendon-to-bone repairs fared equally well, as
      judged by the criteria used here.

PMID- 12070492
TI  - A comparison of clinical estimation, ultrasonography, magnetic resonance imaging,
      and arthroscopy in determining the size of rotator cuff tears.
AB  - This prospective study was undertaken to compare the ability of clinical
      estimation, diagnostic ultrasonography, magnetic resonance imaging, and
      arthroscopy to estimate the size of rotator cuff tears. Estimates of rotator cuff
      tear size were compared with the findings at open operation in 33 consecutive
      patients with a presumptive diagnosis of rotator cuff tear. Arthroscopy estimates
      of rotator cuff tear size correlated best with actual tear size (Pearson
      correlation coefficient r = 0.92; P <.001). Magnetic resonance imaging (r = 0.74;
      P <.001) was similar to ultrasonography (r = 0.73; P <.001). Estimates of rotator
      cuff tear size after clinical assessment alone had weaker correlation
      coefficients (r = 0.41; P =.02) than the other methods. Each method
      underestimated rotator cuff tear size by 12%, 30%, 33%, and 38%, respectively. No
      method was able to determine the size of partial-thickness rotator cuff tears (r
      < 0.02).

PMID- 12070493
TI  - Treatment of acromioclavicular joint separation: suture or suture anchors?
AB  - This investigation compared the stability of 2 methods of fixation for
      acromioclavicular (AC) joint separations. A complete AC joint separation was
      simulated in 6 matched pairs of fresh-frozen human cadaveric shoulders. One
      specimen from each pair was repaired with two No. 5 nonabsorbable braided sutures
      passed around the base of the coracoid and the other with 2 suture anchors
      preloaded with the same suture material placed into the base of the coracoid
      process. The specimens were cyclically loaded for 10(4) cycles to simulate our
      early postoperative rehabilitation protocol for coracoclavicular repairs. Before
      cycling, the repairs had a mean superior laxity of 1.68 +/- 0.44 mm for the
      sutures alone and 1.23 +/- 0.31 mm for the suture anchors. After 10(4) cycles,
      the laxity was 1.32 +/- 0.59 mm and 1.33 +/- 0.94 mm, respectively. These
      differences were not statistically significant (P =.2). This study demonstrated
      that similar stability can be achieved for coracoclavicular fixation with suture
      anchors or with sutures placed around the base of the coracoid for the treatment
      of AC joint separations. The clinical relevance includes the following: (1) the
      potentially diminished risk of neurovascular injury with the use of suture
      anchors compared with the passage of sutures around the base of the coracoid and
      (2) the potentially reduced surgical time associated with the use of suture
      anchors.

PMID- 12070494
TI  - The role of arthroscopy for the problem shoulder arthroplasty.
AB  - Between 1995 and 2000, 29 patients who had excessive pain or limitation of motion
      after a shoulder arthroplasty underwent arthroscopy. Preoperative diagnoses of
      impingement syndrome in 10 patients (treated by arthroscopic subacromial
      decompression), large rotator cuff tear in 1, loose bodies in 1, unstable cuff
      arthropathy in 1, and septic arthritis in another were confirmed at arthroscopy.
      Of the 15 patients without a preoperative diagnosis, 7 had postarthroplasty
      capsular fibrosis, with 6 undergoing arthroscopic capsular release. A
      malpositioned glenoid component was found in 1 patient. Loose or worn components
      were found in 4 of the shoulders, impingement with a small partial-thickness cuff
      tear was identified in 1, a florid synovitis was present in another, and in 1 no
      abnormality could be found. The procedures were often hindered by limited access
      and reflection from the prosthesis. Arthroscopy after shoulder arthroplasty is
      useful for the diagnosis and treatment of pain and loss of motion in selected
      patients but can be technically challenging.

PMID- 12070495
TI  - An alternative portal for scapulothoracic arthroscopy.
AB  - Access to the superior angle of the scapula during scapulothoracic arthroscopy
      with current standard portals can be difficult. A safe, effective alternative
      portal for scapulothoracic arthroscopy, located superior to the scapula, is
      described, which enables easier resection of the superomedial angle for treatment
      of the snapping scapula.

PMID- 12070496
TI  - The effect of fibrin clot on healing rat supraspinatus tendon defects.
AB  - The possibility that fibrin clot, with its chemotactic and mitogenic factors,
      might improve the healing of a defect in the rat supraspinatus tendon was
      evaluated. Bilateral defects were surgically created in the rat supraspinatus
      tendon near the humeral insertion. One defect in each rat was filled with fibrin
      clot from a donor animal while the other side acted as a control. The tendons
      were evaluated at 3, 6, and 12 weeks. On histologic evaluation persistent defects
      were seen at all time points, whereas the healing tissue became less cellular
      with better collagen organization over time. Fibrin clot remained in the healing
      defects of treated shoulders at early time points. Biomechanically, there was
      improvement of properties over time, but they did not approach those of normal
      tendon by 12 weeks. There was no effect from addition of the fibrin clot except
      at 3 weeks, where it led to a decrease in material properties.

PMID- 12070497
TI  - Partial medial epicondylectomy for cubital tunnel syndrome: Outcome and
      complications.
AB  - The results of partial medial epicondylectomy for cubital tunnel syndrome were
      evaluated in 60 elbows of 54 patients. Preoperatively, 8 patients were grade I,
      24 grade IIA, 16 grade IIB, and 12 grade III according to the modified McGowan
      score (Goldberg BJ et al. JHand Surg [Am] 1989;14:182-8). Mean follow-up was 38.8
      months. Special emphasis was placed on evaluation of 5 commonly reported
      drawbacks: medial elbow pain was related to the end result (P <.01), nerve
      vulnerability/subluxation might contribute to pain (P <.05), loss of force
      (approximately 15%) had no clinical implication, and flexion contracture and
      valgus instability were present in only 1 elbow. Eighty-three percent of our
      patients were better according to the Wilson and Krout score,(22) with 75% having
      excellent and good results. An improvement of at least 1 McGowan grade was
      obtained in 88.3%. The chance for complete recovery was inversely related to the
      initial neuropathy grade, as is consistently found throughout the literature for
      all types of cubital tunnel surgery. Partial medial epicondylectomy is a valuable
      surgical procedure for treating grade I to IIB ulnar neuropathy.

PMID- 12070498
TI  - Bone destruction patterns of the rheumatoid elbow: a radiographic assessment of
      148 elbows at 15 years.
AB  - A cohort of 74 patients with rheumatoid arthritis (RA) was followed prospectively
      for 15 years. At the end of the study, 148 elbows were radiographed with standard
      methods. The bone destruction of the humerus was measured from the
      anteroposterior (AP) radiograph as the bone attrition of the trochlea (TM) and
      the capitellum (CM). The bone destruction of the ulna was measured from the AP
      radiograph as the width (WO) and from the lateral radiograph as the thickness
      (TO) of the olecranon. Moreover, elbow joint destruction was graded by the Larsen
      system on a scale of 0 to 5. The relation of bone destruction to Larsen grade of
      the elbows was examined. The mean TM of the nonaffected (Larsen grades 0 to 1, n
      = 73) joints was 17.5 mm (SD, 2.1 mm; range, 10-22 mm), whereas the mean of
      Larsen grade 3 to 5 joints (n = 26) was 11.5 mm (SD, 5.2 mm). The mean CM of the
      nonaffected joints was 19.6 mm (SD, 2.6 mm; range, 15-25 mm), and the
      corresponding mean of Larsen grade 3 to 5 joints 15.5 mm (SD, 4.5 mm). The mean
      TO of the nonaffected joints was 18.9 mm (SD, 1.5 mm; range, 17-23 mm), and the
      mean of Larsen grade 3 to 5 joints was 13.9 mm (SD, 4.1 mm). The mean WO of the
      nonaffected joints was 23.3 (SD, 2.4 mm; range, 18-28 mm), and the mean of Larsen
      grade 3 to 5 joints was 22.4 mm (SD, 6.2 mm). Spearman correlation coefficients
      between TM, CM, and TO and Larsen grade of the joint were -0.45 (95% CI, -0.31 to
      -0.57), -0.38 (95% CI, -0.23 to -0.51), and -0.46 (95% CI, -0.31 to -0.57),
      respectively. Bone destruction in both the humerus and the olecranon appears to
      be a late consequence of rheumatoid elbow involvement. Bone loss is always
      present in the situation of rheumatoid elbow replacement, and it is most
      remarkable in Larsen grade 5 joints; the risk of preoperative and intraoperative
      complications due to bone destruction is significantly increased in this group.

PMID- 12070499
TI  - A biomechanical study of stability of the elbow to valgus stress before and after
      reconstruction of the medial collateral ligament.
AB  - The purpose of this study was to assess the stability of the elbow to valgus
      loads after reconstruction of the anterior bundle of the medial collateral
      ligament (MCL). The MCL in 14 human cadaveric elbows was exposed with a muscle
      splitting approach. Each sample was secured in a materials test frame,5 N-m
      valgus moments were applied in 30 degrees, 60 degrees, 90 degrees, and 120
      degrees of flexion, and baseline stability was measured. This sequence was
      performed after the anterior bundle was sectioned and again after ligamentous
      reconstruction was done with the Jobe technique. At 30 degrees, 60 degrees, 90
      degrees, and 120 degrees of flexion, reconstruction reproduced an average of 99%,
      102%, 97%, and 89%, respectively, of the stability of the intact ligament. The
      only significant difference between intact and reconstructed samples was at 120
      degrees of flexion (P <.05). We concluded that this procedure reliably restores
      stability to a ruptured MCL throughout the flexion arc in the immediate
      postoperative period.

PMID- 12070500
TI  - Biomechanical evaluation of braces used for the treatment of epicondylitis.
AB  - The purpose of the study was to investigate the biomechanical effects of
      different types of braces that are used in the treatment of patients with
      epicondylitis radialis. Vibration and acceleration of the forearm and the elbow
      were measured with sensors taped to defined anatomic points on the skin surface.
      The impact-induced vibration of the racket-arm system was analyzed while the
      subjects were playing tennis. Different designed brace systems were investigated
      with respect to acceleration amplitudes and acceleration integrals. Clasp-based
      brace systems showed a slight reduction of acceleration amplitudes (-6%) and
      acceleration integrals (-8%). Braces with pads at the lateral epicondyle reduced
      acceleration amplitudes by 20% and acceleration integrals by 22%. Braces with
      pads placed at the forearm showed the highest reduction of acceleration
      amplitudes (-46%) and acceleration integrals (-42%). Overload of the wrist
      extensors, which is considered to be a major pathogenic factor in lateral
      epicondylitis, can be reduced by braces. There is a significant difference in the
      effects among different biomechanical principles of braces.

PMID- 12070501
TI  - Subclavian vein obstruction caused by an unreduced type II Salter Harris injury
      of the medial clavicular physis.

PMID- 12070502
TI  - Pigmented villonodular synovitis of the elbow in a 6-year-old girl.

PMID- 12070503
TI  - Compression of the brachial plexus in a patient with false aneurysm of the
      axillary artery as a result of anterior shoulder dislocation.

PMID- 12070504
TI  - The posterior subdeltoid approach: a modified access to the posterior
      glenohumeral joint.

PMID- 12070505
TI  - Nontraumatic osteonecrosis of the humeral head.
AB  - The humeral head is the second most common site for nontraumatic osteonecrosis
      after the femoral head, yet it has attracted relatively little attention.
      Osteonecrosis is associated with many conditions, such as corticosteroid use,
      sickle-cell disease, alcoholism, dysbarism (or caisson disease), Gaucher's
      disease, and other systemic conditions. The diagnosis is a clinical and
      radiographic one, the latter forming the basis for its staging. Treatment depends
      on the chronicity and severity of symptoms, as well as the degree of clinical and
      radiographic progression. Surgical treatment includes arthroscopic debridement
      and core decompression for early osteonecrosis and hemiarthroplasty or total
      shoulder arthroplasty for more advanced disease. This report reviews
      osteonecrosis of the humeral head, with an emphasis on current treatment options.

PMID- 12070506
TI  - The use of chairside silica coating for different dental applications: a clinical
      report.
AB  - This article describes an alternative approach to conditioning an alloy surface
      prior to veneering with composite. The procedure is based on silica coating and
      silanization of the alloy surface, which can be performed chairside.

PMID- 12070508
TI  - Incorporation of an ERA attachment for obturator framework design: a clinical
      report.
AB  - Swinglock framework designs have been used to retain obturators for some time.
      One of the problems with Swinglock designs has been loss of retention due to wear
      of the metal latch assembly. This clinical report describes the incorporation of
      an ERA attachment as the latch assembly of a Swinglock framework for an
      obturator. The premise behind this design was that wear would be at the expense
      of the nylon retention male component, which is easily interchangeable, rather
      than the metal component of the assembly. The life of the latch assembly,
      framework, and prosthesis would thereby be prolonged.

PMID- 12070507
TI  - Conversion of a complete denture to a provisional implant-supported, screw
      retained fixed prosthesis for immediate loading of a completely edentulous arch.
AB  - This article describes the fabrication of a provisional implant-supported, screw
      retained restoration for immediate loading of a completely edentulous arch. The
      technique can be applied to patients with partially edentulous arches as well.
      Until immediate loading of dental implants becomes a well-documented treatment
      modality, the described method should not be applied on a routine basis or
      without careful evaluation.

PMID- 12070509
TI  - Histologic evaluation of a hydroxyapatite onlay bone graft retrieved after 9
      years: a clinical report.
AB  - Because of the limited observations of published studies, the condition of
      hydroxyapatite after a long period of intraoral function remains a concern. This
      clinical report describes the histologic evaluation of a 9 year-old
      hydroxyapatite specimen retrieved from a human subject. The residual
      hydroxyapatite particles showed no sign of resorption, and tight contact with the
      surrounding bone was observed.

PMID- 12070510
TI  - Factors affecting the survival of implants placed in grafted maxillary sinuses: a
      clinical report.
AB  - Many factors affect the survival rate of osseointegrated implants placed in
      grafted maxillary sinuses. This clinical report describes the retrospective
      evaluation of 60 patients with 228 implants placed in 84 grafted maxillary
      sinuses at the Loma Linda University School of Dentistry. The factors used to
      determine the survival rates of these implants were implant type,
      simultaneous/delayed implant placement, pretreatment bone height, oral hygiene,
      and cigarette smoking habits. Out of the total 228 implants, 205 (89.9%) remained
      in function after a mean follow-up period of 41.6 months (range 0 to 60 months).
      A higher failure rate was associated with the use of non-threaded implants, poor
      oral hygiene, and smoking. This information may facilitate treatment planning and
      enhance communication between the dentist and patient regarding the risk/benefit
      ratio and outcomes of implants placed in grafted maxillary sinuses.

PMID- 12070511
TI  - Dietary intake in edentulous subjects with good and poor quality complete
      dentures.
AB  - STATEMENT OF PROBLEM: Previous studies in complete denture wearers evaluated the
      relationship between diet and measures of chewing, yet only isolated nutrient
      intake was considered. This limited information makes the assessment of overall
      diet quality and the planning of interventions difficult. PURPOSE: This study
      investigated the relationship of complete denture quality to masticatory
      performance, perceived ability to chew, and diet quality as measured by the
      Healthy Eating Index (HEI), an overall diet quality index. MATERIAL AND METHOD:
      The study population comprised 54 complete denture wearers. Data were obtained
      from clinical examinations, masticatory performance measurements, and 2 non
      consecutive 24-hour dietary recalls. (Masticatory performance data were not
      collected for 9 subjects because of time constraints, patient fatigue, or patient
      refusal. Statistical analysis showed no significant effect of their absence on
      the reported findings.) Based on a composite rating scale, subjects were divided
      into 3 denture quality groups described as good, medium, and poor. The outcome
      variables were the HEI and its components, plus selected nutrient and non
      nutrient intake. Explanatory variables were quality of complete dentures,
      masticatory performance, and reported chewing ability. Data were analyzed with
      Kruskal-Wallis tests, Mann-Whitney U-tests, and Fisher exact tests. Because a
      large number of dietary components were examined, results were considered
      significant at alpha=.01. RESULTS: Masticatory performance and perceived ability
      to chew were unrelated to diet quality. The good quality denture group had
      significantly better masticatory performance than the medium and poor quality
      groups, but the median HEI scores and dietary intakes were not significantly
      different among these 3 groups. Milk, vegetable, fruit, and grain intake scores
      were mainly responsible for the low overall HEI scores. CONCLUSION: In the
      population evaluated, complete denture quality, food comminution capacity, and
      perceived chewing ability were not related to diet quality. The majority of
      subjects had deficient diets regardless of the technical quality of their
      dentures.

PMID- 12070512
TI  - Tensile strength of type IV dental stones dried in a microwave oven.
AB  - STATEMENT OF PROBLEM: It is known that drying dental stones in a microwave oven
      can save time, but the strength of the material may be affected by different
      drying methods. PURPOSE: This study evaluated the diametral tensile strength
      (DTS) of 5 type IV gypsum products at different time intervals using microwave
      and air-drying methods. MATERIAL AND METHOD: . A total of 300 cylinder specimens
      were prepared from 5 type IV dental stones (Moldano, Amberok, Herastone, Shera
      Sockel, and Fujirock; n = 60 per stone) in accordance with the manufacturers'
      recommendations. Half of the specimens of each stone (n = 30) were dried in open
      air within a temperature range of 20 +/- 2 degrees C; the other half (n = 30)
      underwent initial setting in a silicone rubber mold in open air for 10 minutes
      and then were dried in a microwave oven for 10 minutes. Within these groups, 10
      specimens were tested under diametral compression at each of the following time
      periods: 30, 60, and 120 minutes after drying. Three-way analysis of variance and
      Scheffe's post hoc test were performed for statistical comparisons at a
      significance level of P<.05. RESULTS: At all time intervals, the diametral
      tensile strength values for dental stones dried in a microwave oven (mean 2.99
      MPa) were significantly higher (P<.01) than the values for specimens dried in
      open air (mean 2.53 MPa). CONCLUSION: Within the limitations of this study,
      microwave oven drying had a positive effect on the diametral tensile strength of
      5 type IV dental stones.

PMID- 12070513
TI  - Tooth structure removal associated with various preparation designs for anterior
      teeth.
AB  - STATEMENT OF PROBLEM: The conservation of sound tooth structure helps preserve
      tooth vitality and reduce postoperative sensitivity. Innovative preparation
      designs, like those for porcelain laminate veneers, are much less invasive than
      conventional complete-coverage crown preparations. However, no study has
      quantified the amount of tooth structure removed during these preparations.
      PURPOSE: The purpose of this study was to quantify and compare the amount of
      tooth structure removed when various innovative and conventional tooth
      preparation designs were completed on different teeth. MATERIAL AND METHOD: . A
      new comprehensive tooth preparation design classification system was introduced.
      Typodont resin teeth representing the maxillary left central incisor, maxillary
      left canine, and mandibular left central incisor were prepared with the following
      designs: partial (V1), traditional (V2), extended (V3), and complete (V4)
      porcelain laminate veneer preparations; resin-bonded retainer preparation with
      grooves (A1) and with wing/grooves (A2); all-ceramic crown preparation with 0.8
      mm axial reduction and tapering chamfer finish line (F1), all-ceramic crown
      preparation with 1.0 mm axial reduction and rounded shoulder finish line (F2),
      and metal-ceramic crown with 1.4 mm axial reduction and facial shoulder finish
      line (F3). After tooth preparations (10 per group), the crown was separated from
      the root at the CEJ. The removed coronal tooth structure was measured with
      gravimetric analysis. Means and standard deviations for tooth structure removal
      with different preparation designs were calculated and analyzed with analysis of
      variance at a significance level of P<.05. RESULTS: Significant differences in
      the amount of tooth structure removal were noted between preparation designs.
      Ceramic veneers and resin-bonded prosthesis retainers were the least invasive
      preparation designs, removing approximately 3% to 30% of the coronal tooth
      structure by weight. Approximately 63% to 72% of the coronal tooth structure was
      removed when teeth were prepared for all-ceramic and metal-ceramic crowns. For a
      single crown restoration, the tooth structure removal required for an F3
      preparation (metal-ceramic crown) was 4.3 times greater than for a V2 preparation
      (porcelain laminate veneer, facial surface only) and 2.4 times greater than for a
      V4 preparation (more extensive porcelain laminate veneer). CONCLUSION: Within the
      limitations of this study, tooth preparations for porcelain laminate veneers and
      resin-bonded prostheses required approximately one-quarter to one-half the amount
      of tooth reduction of conventional complete-coverage crowns.

PMID- 12070514
TI  - A clinical pilot study of the dimensional accuracy of double-arch and complete
      arch impressions.
AB  - STATEMENT OF PROBLEM: It has been suggested that articulated casts fabricated
      with the double-arch impression technique may have superior occlusal accuracy
      than those fabricated with a single complete-arch impression. However, lack of
      tray rigidity may lead to flexure of the impression/tray complex, resulting in
      inaccurate dies in the bucco-lingual dimension. PURPOSE: This clinical pilot
      study compared the dimensions of dies fabricated with 3 types of double-arch
      impressions to dies fabricated with the conventional complete-arch, custom tray
      method. MATERIAL AND METHODS: Thirty-five addition silicone impressions were made
      of cast metal copings cemented onto natural teeth prepared as complete-crown
      abutments. Four combinations of tray types and impression material viscosity were
      used: (1) complete-arch, custom acrylic trays loaded with heavy-bodied material;
      (2) double-arch, disposable plastic trays loaded with heavy-bodied material; (3)
      double-arch, disposable plastic trays loaded with putty material; and (4) double
      arch, reusable brass metal trays loaded with heavy-bodied material. Immediately
      prior to tray insertion, light-bodied impression material was syringed over all
      copings as a wash. The 4 copings were fabricated from cast gold and simulated
      metal-ceramic complete-crown thimbles with polished collars and had "projections"
      on the occlusal surfaces. The impressions were poured in type IV die-stone. Bucco
      lingual and inter-abutment dimensions were measured. The differences between the
      stone dimensions and cast metal control dimensions were calculated and converted
      to percent dimensional change. The data were analyzed with 1-way analysis of
      variance, Student t tests, and Mann-Whitney tests (P<.05). RESULTS: The plastic
      double-arch tray loaded with heavy-viscosity addition silicone and a low
      viscosity wash produced the least accurate combination inter- and intra-abutment
      dimensions. For this protocol, 1.17% mean dimensional change was recorded. This
      result was significantly different than that obtained for the other 3 impression
      methods tested. No significant differences were found between the complete-arch
      method and protocols in which putty was loaded in a plastic or metal tray.
      CONCLUSION: Within the limitations of this pilot study, the more rigid
      tray/impression material combinations more accurately replicated stone dies.

PMID- 12070515
TI  - Stress distribution of inlay-anchored adhesive fixed partial dentures: a finite
      element analysis of the influence of restorative materials and abutment
      preparation design.
AB  - STATEMENT OF PROBLEM: Indirect composite or ceramic fixed partial dentures (FPDs)
      have become an alternative to conventional metal-ceramic adhesive fixed partial
      dentures (AFPDs). Little information about the adequate restorative material and
      tooth preparation design for inlay-anchored AFPDs is available to the clinician.
      PURPOSE: The purposes of this simulation study were: (1) to use 2-dimensional
      finite element modeling to simulate stresses at the surface and interface of 3
      unit posterior AFPDs made with 6 different restorative materials, and (2) to
      investigate the influence of 3 different abutment preparation configurations on
      the stress distribution within the tooth/restoration complex. MATERIAL AND
      METHODS: A mesio-distal cross-section of a 3-unit AFPD was digitized and used to
      create 2-dimensional models of the periodontal membrane, supporting bone,
      different restorative materials (gold, alumina, zirconia, glass-ceramic,
      composite, and fiber-reinforced composite), and different abutment preparation
      configurations (interproximal slots vs. 2-surface [MO, DO] vs. 3-surface [MOD]).
      A simulated 50-N vertical occlusal load was applied to the standardized pontic
      element. The principal stress within the restorative materials, stresses at the
      tooth/restoration interface, and surface tangential stresses at the level of the
      pontic were calculated in MPa from the postprocessing files and compared to each
      other. RESULTS: All materials and tooth preparation design exhibited a similar
      stress pattern, with a definite compressive area at the occlusal side of the
      pontic, a tensile zone at the gingival portion of the pontic, and tensile stress
      peaks in the abutment/pontic connection areas. Among isotropic materials,
      standard non-reinforced composites exhibited better stress transfer and reduced
      tensile stresses at the adhesive interface than ceramics and gold. Optimized
      placement of the glass fibers within the composite resulted in similar stress
      distribution when tested in 2-surface abutment preparation configuration. There
      was no detectable influence of preparation design on the behavior of the pontic
      area. Among all 3 preparation designs, only the DO design exhibited almost pure
      compression at the interface. CONCLUSION: Within the limitations of this
      simulation experiment, the composite materials tested demonstrated a resilient
      component that favored stress transfer within the tooth/restoration complex.
      Their clinical use, however, may be contraindicated due to insufficient strength
      and fracture toughness. The addition of extremely tough fibers to composites
      represents the most promising combination. Clinical trials are required to ensure
      that veneering composite can survive under clinical conditions.

PMID- 12070516
TI  - Effect of splinting and interproximal contact tightness on load transfer by
      implant restorations.
AB  - STATEMENT OF PROBLEM: To circumvent the difficulty of achieving a passive
      framework fit, some authors have suggested that multiple adjacent implants be
      restored individually. This protocol requires that each unit be able to withstand
      mastication forces. Non-splinted restorations have numerous interproximal
      contacts that require adjustments prior to placement, with an unknown outcome
      relative to load transfer. PURPOSE: This in vitro simulation study examined the
      effect of splinting and interproximal contact tightness on passivity of fit and
      the load transfer characteristics of implant restorations. MATERIAL AND METHODS:
      A photoelastic model of a human partially edentulous left mandible with 3 screw
      type implants (3.75 x 10 mm) was fabricated. For non-splinted restorations,
      individual crowns were fabricated on 3 custom-milled titanium abutments. After
      the units were cemented, 5 levels of interproximal contact tightness were
      evaluated: open, ideal (8 microm shim stock drags without tearing), light (ideal
      +10 microm), medium (ideal + 50 microm), and heavy (ideal + 90 microm). For
      splinted restorations, five 3-unit fixed partial dentures were fabricated,
      internally adjusted with silicone disclosing material, and cemented to the model.
      Changes in stress distribution under simulated non-loaded and loaded conditions
      (6.8 kg) were analyzed with a polariscope. RESULTS: In the simulated alveolar
      structures, non-splinted restorations with heavier interproximal contacts were
      associated with increased tensile stresses between implants; occlusal loads
      tended to concentrate around the specific loaded implant. Splinted restorations
      shared the occlusal loads and distributed the stresses more evenly between the
      implants when force was applied. The load-sharing effect was most evident on the
      center implant but also was seen on the terminal abutments of the splinted
      restorations. CONCLUSION: The results of this in vitro study suggest that
      excessive contact tightness between individual crowns can lead to a non-passive
      situation. In this experiment, splinted restorations exhibited better load
      sharing than non-splinted restorations.

PMID- 12070517
TI  - Effect of connector design on the fracture resistance of all-ceramic fixed
      partial dentures.
AB  - STATEMENT OF PROBLEM: Fracture of all-ceramic fixed partial dentures (FPDs) tends
      to occur in the connector area. PURPOSE: The objective of this study was to test
      the hypothesis that the radii of curvature at the connector affects the fracture
      resistance of 3-unit FPDs. MATERIAL AND METHODS: With the use of a standardized
      silicone mold, 40 three-unit FPD wax patterns were fabricated with the same
      dimensions and divided into 4 groups of 10 specimens per group. Each pattern was
      modified at the connector areas of the occlusal embrasure (OE) and the gingival
      embrasure (GE); 2 wax carvers with radii of curvature at their tips of 0.90 mm
      and 0.25 mm were used. The dimensions of the connectors were standardized with an
      electronic caliper to 4 +/- 0.12 mm in height and 5 +/- 0.13 mm in width.
      Connector designs were as follows: Design I: OE and GE 0.90 mm; Design II: OE
      0.90 mm and GE 0.25 mm; Design III: OE 0.25 mm and GE 0.90 mm; and Design IV
      (control): OE and GE 0.25 mm. An experimental hot-pressed core ceramic was used
      to make the FPD frameworks, which were consequently cemented on epoxy dies with
      dual-polymerizing composite (Variolink II) and loaded to fracture in a universal
      testing machine at a crosshead speed of 0.5 mm/min. The failure load data were
      analyzed with analysis of variance (ANOVA; P=.05) and Duncan's test (alpha=.01).
      RESULTS: The mean failure loads and standard deviations were as follows: 943 +/-
      151 N for Design I; 746 +/- 106 N for Design II; 944 +/- 144 N for Design III;
      and 673 +/- 55 N for Design IV. ANOVA revealed a significant difference (P< or =
      .0001) between the mean failure loads of different connector designs. The mean
      loads to failure for Designs I and III were significantly higher than those for
      Designs II and IV (Duncan's test). CONCLUSION: Within the limitations of this
      study and for the experimental ceramic tested, as the radius at the gingival
      embrasure increased from 0.25 to 0.90 mm, the mean failure load increased by
      140%. The radius of curvature at the occlusal embrasure had only a minor effect
      on the fracture susceptibility of 3-unit FPDs.

PMID- 12070518
TI  - Macro design morphology of endosseous dental implants.
AB  - STATEMENT OF PROBLEM: The identification of dental implant bodies in patients
      without available records is a considerable problem due to increased patient
      mobility and to the large number of implant systems with different designs.
      PURPOSE: The purpose of this study was to document the designs of selected
      implants to help clinicians identify these implants from their radiographic
      images. MATERIAL AND METHODS: More than 50 implant manufacturers were contacted
      and asked to provide implants with dimensions as close as possible to 3.75 mm
      (diameter) x 10 mm (length). Forty-four implants were donated, separated into
      threaded and non-threaded categories, and further sorted into tapered and non
      tapered categories. The implants were examined visually, and features on the
      entire circumference and length of each implant were recorded and categorized as
      coronal, midbody, or apical. RESULTS: A series of tables describe the 44 implants
      according to coronal, midbody, and apical features. CONCLUSION: The results of
      this project offer dentists basic knowledge of the design of selected dental
      implants. Such knowledge can aid the radiographic identification of these
      implants.

PMID- 12070519
TI  - Radiographic identification of nonthreaded endosseous dental implants.
AB  - STATEMENT OF PROBLEM: The identification of dental implant bodies in patients
      without available records is a considerable problem due to increased patient
      mobility and to the large number of implant systems with different designs.
      PURPOSE: The purpose of this study was to document features that would help
      dentists identify non-threaded implant bodies from their radiographic images.
      MATERIAL AND METHODS: More than 50 implant manufacturers were contacted and asked
      to provide implants with dimensions as close as possible to 3.75 mm (diameter) x
      10 mm (length). Forty-four implants were donated, 16 of which were identified as
      non-threaded. Radiographs were made of these implants at 0 degrees, 30 degrees,
      60 degrees, and 90 degrees horizontal rotation combined with -20 degrees, -10
      degrees, 0 degrees, +10 degrees, and +20 degrees vertical inclination relative to
      the radiographic beam and film. A total of 20 images per implant were taken and
      examined to identify consistent, unique features that would aid in implant
      identification. At a 20 degrees vertical inclination, vital features of implants
      were distorted enough to be deemed unrecognizable. Therefore, only those
      observations made from radiographs between -10 degrees and +10 degrees vertical
      inclination were used for implant identification purposes. RESULTS: All implants
      could be recognized from radiographs made between -10 degrees and +10 degrees
      vertical inclination. A series of tables and flowcharts describe the implants
      according to their identifying features. CONCLUSION: Information from this study
      should help dentists identify non-threaded endosseous implants from their
      radiographic images.

PMID- 12070520
TI  - Radiographic identification of threaded endosseous dental implants.
AB  - STATEMENT OF PROBLEM: The identification of dental implant bodies in patients
      without available records is a considerable problem due to increased patient
      mobility and to the large number of implant systems with different designs.
      PURPOSE: The purpose of this study was to document features that would help
      dentists identify threaded implant bodies from their radiographic images.
      MATERIAL AND METHODS: More than 50 implant manufacturers were contacted and asked
      to provide implants with dimensions as close as possible to 3.75 mm (diameter) x
      10 mm (length). Forty-four implants were donated, 28 of which were identified as
      threaded. Radiographs were made of these implants at 0 degrees, 30 degrees, 60
      degrees, and 90 degrees horizontal rotation combined with -20 degrees, -10
      degrees, 0 degrees, +10 degrees, and +20 degrees vertical inclination relative to
      the radiographic beam and film. A total of 20 images per implant were taken and
      examined to identify consistent, unique features that would aid in implant
      identification. At a 20 degrees vertical inclination, vital features of implants
      were distorted enough to be deemed unrecognizable. Therefore, only those
      observations made from radiographs between -10 degrees and +10 degrees vertical
      inclination were used for implant identification purposes. RESULTS: All implants
      could be recognized from radiographs made between -10 degrees and +10 degrees
      vertical inclination. A series of tables and flowcharts describe the implants
      according to their identifying features. CONCLUSION: Information from this study
      should help dentists identify threaded endosseous implants from their
      radiographic images.

PMID- 12070521
TI  - A light-polymerized resin support tray as an aid for recording centric relation.
AB  - For patients who require complex fixed prosthodontic oral rehabilitation,
      recording an accurate centric relation is often a difficult procedure. A minimal
      number of abutment teeth or implants may not offer adequate support for the
      occlusal registration material. In the described technique, Triad tray material
      is used as an occlusal registration supporting tray. This procedure is accurate
      and convenient for the restorative dentist.

PMID- 12070522
TI  - Quick chairside diagnostic wax-up.

PMID- 12070524
TI  - Neuroprotective profile of enoxaparin, a low molecular weight heparin, in in vivo
      models of cerebral ischemia or traumatic brain injury in rats: a review.
AB  - The development of treatments for acute neurodegenerative diseases (stroke and
      brain trauma) has focused on (i) reestablishing blood flow to ischemic areas as
      quickly as possible (i.e. mainly antithrombotics or thrombolytics for stroke
      therapy) and (ii) on protecting neurons from cytotoxic events (i.e.
      neuroprotective therapies such as anti-excitotoxic or anti-inflammatory agents
      for stroke and neurotrauma therapies). This paper reviews the preclinical data
      for enoxaparin in in vivo models of ischemia and brain trauma in rats. Following
      a photothrombotic lesion in the rat, enoxaparin significantly reduced edema at 24
      h after lesion when the treatment was started up to 18 h after insult. Enoxaparin
      was also tested after an ischemic insult using the transient middle cerebral
      artery occlusion (tMCAO) model in the rat. Enoxaparin, 2 x 1.5 mg/kg i.v.,
      significantly reduced the lesion size and improved the neuroscore when the
      treatment was started up to 5 h after ischemia. Enoxaparin, administered at 5 h
      after insult, reduced cortical lesion size in a dose-dependent manner. In
      permanent MCAO, enoxaparin (5 and 24 h after insult) significantly reduced lesion
      size and improved neuroscore. A slight and reversible elevation of activated
      partial thromboplastin time (APTT) suggests that enoxaparin is neuroprotective at
      a non-hemorrhagic dose. Traumatic brain injury (TBI) is often accompanied by
      secondary ischemia due in part to edema-induced compression of blood vessels.
      When enoxaparin, at 0.5 mg/kg i.v. + 4 x 1 mg/kg s.c., was administered later
      than 30 h after TBI, it significantly reduced edema in hippocampus and parietal
      cortex. At one week after TBI the lesion size was significantly reduced and the
      neurological deficit significantly improved in enoxaparin treated animals.
      Finally, the cognitive impairment was significantly improved by enoxaparin at 48
      h to 2 weeks after TBI. The anticoagulant properties of unfractionated heparin
      and specifically enoxaparin can explain their anti-ischemic effects in
      experimental models. Furthermore, unfractionated heparin and specifically
      enoxaparin, have, in addition to anticoagulant, many other pharmacological
      effects (i.e. reduction of intracellular Ca2+ release; antioxidant effect; anti
      inflammatory or neurotrophic effects) that could act in synergy to explain the
      neuroprotective activity of enoxaparin in acute neurodegenerative diseases.
      Finally, we demonstrated, that in different in vivo models of acute
      neurodegenerative diseases, enoxaparin reduces brain edema and lesion size and
      improves motor and cognitive functional recovery with a large therapeutic window
      of opportunity (compatible with a clinical application). Taking into account
      these experimental data in models of ischemia and brain trauma, the clinical use
      of enoxaparin in acute neurodegenerative diseases warrants serious consideration.

PMID- 12070525
TI  - S 17092: a prolyl endopeptidase inhibitor as a potential therapeutic drug for
      memory impairment. Preclinical and clinical studies.
AB  - Any treatment that could positively modulate central neuropeptides levels would
      provide a promising therapeutic approach to the treatment of cognitive deficits
      associated with aging and/or neurodegenerative diseases. Therefore, based on the
      activity in rodents, S 17092 (2S,3aS,7aS)-1][(R,R)-2-phenylcyclopropyl]carbonyl]
      2-[(thiazolidin-3-yl)carbonyl]octahydro-1H-indole) has been selected as a potent
      inhibitor of cerebral prolyl-endopeptidase (PEP). By retarding the degradation of
      neuroactive peptides, S 17092 was successfully used in a variety of memory tasks.
      These tasks explored short-term, long-term, reference and working memory in aged
      mice, as well as in rodents and monkeys with chemically induced amnesia or
      spontaneous memory deficits. S 17092 has also been safely administered to humans,
      and showed a clear peripheral expression of its mechanism of action through its
      inhibitory effect upon PEP activity in plasma. S 17092 exhibited central effects,
      as evidenced by EEG recording in healthy volunteers, and could improve a delayed
      verbal memory task. Collectively, the preclinical and clinical effects of S 17092
      have suggested a promising role for this compound as an agent for the treatment
      of cognitive disorders associated with cerebral aging.

PMID- 12070526
TI  - CHF2819: pharmacological profile of a novel acetylcholinesterase inhibitor.
AB  - CHF2819 is a novel orally active acetylcholinesterase inhibitor (AChEI) developed
      for the treatment of Alzheimer's disease (AD). CHF2819 is a selective inhibitor
      of AChE, it is 115 times more potent against this enzyme than against
      butyrylcholinesterase (BuChE). Moreover, CHF2819 is more selective for inhibition
      of central (brain) AChE than peripheral (heart) AChE. In vivo CHF2819, 0.5, 1.5,
      and 4.5 mg/kg p.o., significantly and in dose-dependent manner increased
      acetylcholine (ACh) levels in hippocampus of young adult rats. Moreover, aging
      animals, with lower basal ACh levels than young adult rats, also exhibit a marked
      increase in hippocampal levels of this neurotransmitter after administration of
      CHF2819. At 1.5 mg/kg p.o. CHF2819 attenuated scopolamine-induced amnesia in a
      passive avoidance task. Furthermore, it decreased dopamine (DA) levels and
      increased extracellular levels of 5-hydroxytryptamine (5-HT) in the hippocampus,
      without modifying norepinephrine (NE) levels. By oral administration to young
      adult rats CHF2819 did not affect extracellular hippocampal levels of glutamate
      (Glu), aspartate (Asp), gamma-aminobutyric acid (GABA), taurine (Tau), arginine
      (Arg) or citrulline (Cit). Functional observational battery (FOB) screening
      demonstrated that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity,
      excitability, autonomic, neuromuscular, and sensorimotor domains, as well as
      physiological endpoints (body weight and temperature). CHF2819 induced, however,
      involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a
      dose-dependent manner. The neurochemical and behavioral profiles of CHF2819
      suggest that this orally active novel AChEI could be of clinical interest for the
      treatment of Alzheimer-type dementia associated with multiple neurotransmitter
      abnormalities in the brain. In particular, CHF2819 might be a useful therapeutic
      drug for AD patients with cognitive impairment accompanied by depression.

PMID- 12070527
TI  - Aniracetam: its novel therapeutic potential in cerebral dysfunctional disorders
      based on recent pharmacological discoveries.
AB  - Aniracetam is a pyrrolidinone-type cognition enhancer that has been clinically
      used in the treatment of behavioral and psychological symptoms of dementia
      following stroke and in Alzheimer's disease. New discoveries in the behavioral
      pharmacology, biochemistry and pharmacokinetics of aniracetam provided new
      indications for this drug in the treatment of various CNS disorders or disease
      states. This article reviews these new findings and describes the effects of
      aniracetam in various rodent models of mental function impairment or cerebral
      dysfunction. Also, several metabolites of aniracetam have been reported to affect
      learning and memory in animals. It is, therefore, conceivable that major
      metabolites of aniracetam contribute to its pharmacological effects. The animal
      models, used in pharmacological evaluation of aniracetam included models of
      hypoattention, hypovigilance-arousal, impulsiveness, hyperactivity, fear and
      anxiety, depression, impaired rapid-eye movement sleep, disturbed temporal
      regulation, behavioral performance, and bladder hyperactivity. These are models
      of clinical disorders or symptoms that may include personality disorders,
      anxiety, depression, posttraumatic stress disorder, attention
      deficit/hyperactivity disorder, autism, negative symptoms of schizophrenia, and
      sleep disorders. At present, there is no convincing evidence that promising
      effects of aniracetam in the animal models will guarantee its clinical efficacy.
      It is conceivable, however, that clinical trials will demonstrate beneficial
      effects of aniracetam in the above listed disease states. New findings regarding
      the mechanism of action of aniracetam, its central target sites, and its effects
      on signal transduction are also discussed in this review article.

PMID- 12070528
TI  - SB-258741: a 5-HT7 receptor antagonist of potential clinical interest.
AB  - Recently, a series of 5-HT7 receptor antagonists have been developed
      (24,29,36,68). Among them SB-258741, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4
      methylpiperidin-1-yl)ethyl]-pyrrolidine, (compound "13" in 36,37) was one of the
      most potent and specific compounds. Due to a lack of specific ligands the
      pharmacology of 5-HT7 receptor antagonists is still relatively unexplored. It has
      been suggested, however, that 5-HT7 receptor ligands could be useful in the
      therapy of various disorders such as sleep disorders, schizophrenia, depression,
      migraine, epilepsy, pain, or memory impairment. Many of these conceivable
      indications are not supported by pharmacological data. It is, therefore, of
      particular interest to review the data generated from studies of one of these
      most potent and specific 5-HT7 receptor antagonists, SB-258741, with a goal of
      testing the validity of the proposed clinical indications. In this review, the
      author describes pharmacology of this compound in order to define its potential
      clinical use. The available safety pharmacology data are discussed in an attempt
      to predict potential side effects of specific 5-HT7 receptor antagonists.

PMID- 12070529
TI  - (S)-3,5-DHPG: a review.
AB  - 3,5-dihydroxyphenylglycine (3,5-DHPG) was the first agonist shown to be group I
      metabotropic glutamate receptor selective with its agonist effects residing
      exclusively in the S-isomer. Some results suggest that (S)-3,5-DHPG may be a
      partial agonist of mGluR1a and mGluR5a in neurons and astrocytes. It has been
      reported that (S)-3,5-DHPG can, under certain conditions, interact with NMDA
      receptors. (S)-3,5-DHPG exerts different effects on second messengers in adult
      and neonatal tissues. It stimulates phosphoinositide hydrolysis in a dose
      dependent manner in both the adult and neonate hippocampus, inhibits stimulated
      cAMP levels in the adult and enhances the cAMP in the neonate. It is an effective
      antagonist of mGluRs linked to phospholipase D (PLD) in the adult and an agonist
      in the neonate brain or astrocyte cultures. (S)-3,5-DHPG induces elevation of
      [Ca2+]i and regulates multiple subtypes of Ca2+ channels. This agonist of group I
      mGluRs may modulate neurotransmitters release, reflecting the diversity of
      mechanisms involved. Depending on the dose, (S)-3,5-DHPG enhances or decreases
      excitatory postsynaptic potentials (EPSPs) and under appropriate conditions it
      can induce long-term depression (LTD) and long-term potentiation (LTP). Some
      studies suggested a therapeutic role for (S)-3,5-DHPG in neuronal injury,
      regulation of intestinal motility and secretion, learning and memory processes
      and in cardiovascular system. (S)-3,5-DHPG may be useful as a cognitive enhancing
      agent in memory impairment associated with ischemia or hypoxia. Recent
      investigations suggested possible beneficial effects of (S)-3,5-DHPG in
      Alzheimer's disease.

PMID- 12070531
TI  - Potential use of beta(3)-adrenoceptor antagonists in heart failure therapy.
AB  - Recently, a functional, negatively inotropic, beta(3)-adrenoceptor was
      characterized in the human heart. Several studies now suggest that this receptor
      might play an important role in the pathophysiology of heart failure, by
      counterbalancing the effects of a beta(1)- and beta(2)-stimulation. Therefore,
      this review summarizes the rationale and effects of beta-adrenergic blockade in
      chronic heart failure and specifically addresses the question of the potential
      use of beta(3)-adrenoceptor antagonists in the treatment of heart failure and
      other pathophysiological conditions associated with a decreased cardiac
      contractility.

PMID- 12070530
TI  - Endothelin antagonism with bosentan: current status and future perspectives.
AB  - Endothelin receptor antagonists have been proposed for the treatment of a variety
      of disorders in which the endothelins may act as pathogenic mediators, such as
      hypertension, congestive heart failure, and cerebral vasospasm. Bosentan is a
      nonpeptide competitive antagonist, which can be a good tool for studying the
      endothelin system. It is specific for the endothelin system and blocks the
      actions of endothelin at both mammalian receptors (A and B). Bosentan has
      recently moved into Phase III clinical trial. This review will attempt to
      overview the experimental and clinical effects of bosentan.

PMID- 12070532
TI  - Brain natriuretic peptide (nesiritide) in the treatment of heart failure.
AB  - Over the last decade brain natriuretic peptide (BNP) emerged as a cardiac hormone
      of clinical interest in diagnosis, prognosis and treatment of patients with Heart
      Failure (HF). The diagnostic potential of BNP is now well established both in
      patients with suspected HF as well as in patients with asymptomatic left
      ventricular systolic dysfunction. The prognostic information obtained from BNP
      levels in HF and acute myocardial infarction patients seems even more promising.
      Nesiritide is a synthetic peptide, homologous to endogenous BNP. It is a balanced
      vasodilator with diuretic and natriuretic properties. It decreases the elevated
      levels of neurohormones resulting from activation of the sympathetic and renin
      aldosterone systems in HF. The results of clinical trials involving more than
      2000 patients with decompensated HF are now available. In these trials nesiritide
      was administered by single or repeated bolus injections, as well as by sustained
      infusions. Nesiritide has been shown to produce a potent, dose-related
      vasodilator effect that is rapid in onset and sustained during infusion. Balanced
      vasodilation is reflected by decreases in systemic vascular resistance, pulmonary
      artery wedge pressure and right atrial pressure. No tachyphylaxis has been
      observed in these trials. Efficacy of nesiritide in the treatment of
      decompensated HF has been demonstrated. Trials comparing nesiritide with
      conventional treatment of decompensated HF showed that nesiritide compares
      favorably to standard agents. The safety profile has been excellent with a dose
      dependent hypotension as the major side effect. Ventricular arrhythmia was not
      more frequent in patients treated with nesiritide than with placebo. Thus,
      nesiritide appears to be useful as a first-line agent in the treatment of
      patients with decompensated HF.

PMID- 12070533
TI  - Fondaparinux, a synthetic pentasaccharide: the first in a new class of
      antithrombotic agents - the selective factor Xa inhibitors.
AB  - Despite currently available antithrombotic therapies, venous thromboembolism
      (VTE) remains a major cause of morbidity and mortality. Fondaparinux sodium
      (pentasaccharide), the first in a new class of antithrombotic agents developed
      for the prevention and treatment of VTE, inhibits thrombin generation by
      selectively inhibiting factor Xa. Fondaparinux exhibits complete bioavailability
      by the subcutaneous route and is rapidly absorbed, reaching its maximum
      concentration approximately 2 h post dosing. It has a terminal half-life of 13 to
      21 h, permitting once-daily dosing. Fondaparinux's reproducible linear
      pharmacokinetic profile exhibits minimal intrasubject and intersubject
      variability, suggesting that individual dose adjustments will not be required for
      the vast majority of the population and that there will be no need for routine
      hemostatic monitoring. At therapeutic concentrations (<2 mg/L), fondaparinux
      exhibits >94% binding to its target protein, antithrombin. Within this same
      concentration range there is no specific binding by fondaparinux to plasma
      proteins commonly involved in drug binding, indicating a low potential for drug
      drug interactions by protein displacement. Unlike antithrombotic agents prepared
      from animal extracts (heparins), fondaparinux is chemically synthesized; this
      leads to batch-to-batch consistency and the absence of potential risk of
      contamination problems. In recently completed phase III clinical trials in VTE
      prevention in major orthopedic surgery, fondaparinux showed significant
      superiority over the low-molecular-weight heparin enoxaparin, providing an
      overall >50% (P < 0.001) reduction in VTE risk without increasing clinically
      important bleeding. Additional clinical data support its potential benefits in
      other venous and arterial thrombotic disorders. In view of these collective
      findings, fondaparinux is expected to play a major role in the prevention and
      treatment of venous and arterial thrombotic disease.

PMID- 12070534
TI  - BQ-788, a selective endothelin ET(B) receptor antagonist.
AB  - We describe characteristics of a selective endothelin (ET) ET(B) receptor
      antagonist, BQ-788 [N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1
      methoxycarbonyltryptophanyl-D-norleucine], which is widely used to demonstrate
      the role of endogenous or exogenous ETs in vitro and in vivo. In vitro, BQ-788
      potently and competitively inhibited (125)I-labeled ET-1 binding to ET(B)
      receptors in human Girrardi heart cells (hGH) with an IC(50) of 1.2 nM, but only
      poorly inhibited the binding to ET A receptors in human neuroblastoma cell line
      SK-N-MC cells (IC(50), 1300 nM). In isolated rabbit pulmonary arteries, BQ-788
      showed no agonistic activity up to 10 microM and competitively inhibited the
      vasoconstriction induced by an ET(B)-selective agonist (pA(2), 8.4). BQ-788 also
      inhibited several bioactivities of ET-1, such as bronchoconstriction, cell
      proliferation, and clearance of perfused ET-1. Thus, it is confirmed that BQ-788
      is a potent, selective ET(B) receptor antagonist. In vivo, in conscious rats, BQ
      788, 3 mg/kg/h, i.v., completely inhibited a pharmacological dose of ET-1- or
      sarafotoxin6c (S6c) (0.5 nmol/kg, i.v.)-induced ET(B) receptor-mediated
      depressor, but not pressor responses. Furthermore, BQ-788 markedly increased the
      plasma concentration of ET-1, which is considered an index of potential ET(B)
      receptor blockade in vivo. In Dahl salt-sensitive hypertensive (DS) rats, BQ-788,
      3 mg/kg/h, i.v., increased blood pressure by about 20 mm Hg. It is reported that
      BQ-788 also inhibited ET-1-induced bronchoconstriction, tumor growth and
      lipopolysaccharide-induced organ failure. These data suggest that BQ-788 is a
      good tool for demonstrating the role of ET-1 and ET(B) receptor subtypes in
      physiological and/or pathophysiological conditions.

PMID- 12070535
TI  - Role of tissue factor pathway inhibitor in the regulation of tissue factor
      dependent blood coagulation.
AB  - Tissue factor pathway inhibitor (TFPI) is a multivalent, Kunitz-type plasma
      proteinase inhibitor that modulates tissue factor-dependent coagulation in vivo.
      TFPI possesses a peculiar two-step mechanism of action; it directly inhibits
      activated factor X and subsequently produces feedback inhibition of the factor
      VIIa/tissue factor catalytic complex in a factor Xa-dependent fashion. TFPI
      biochemistry and physiology have been extensively studied during the last decade.
      Its pathophysiologic role in thrombotic disorders has, however, only recently
      started to be unraveled. In particular, circulating plasma TFPI levels have been
      found to modulate the activity of the tissue factor-dependent coagulation
      cascade. In animal models, neutralization of circulating TFPI activity results in
      restoration of intravascular thrombus formation previously abolished by aspirin.
      In patients with acute myocardial infarction, TFPI plasma levels measured in
      blood samples obtained from the coronary sinus were significantly lower than
      those measured in blood obtained from the ascending aorta, indicating acute
      consumption of TFPI within the coronary circulation of patients with
      intracoronary thrombosis. Finally, recent data indicate that transfection of the
      arterial wall with the gene coding for TFPI is an effective therapeutic
      intervention to prevent intravascular thrombus formation. Taken together, these
      observations underline the pathophysiologic importance of TFPI in regulating the
      procoagulant activity of tissue factor and open new potential therapeutic
      approaches for the treatment of thrombotic disorders.

PMID- 12070536
TI  - Efonidipine hydrochloride: a dual blocker of L- and T-type ca(2+) channels.
AB  - T-type Ca(2+) channels have properties different from those of the L-type and are
      involved in cardiac pacemaking and regulation of blood flow, but not in
      myocardial contraction. Efonidipine is an antihypertensive and antianginal drug
      with dihydropyridine structure that was recently found to block both L- and T
      type Ca(2+) channels. In isolated myocardial and vascular preparations,
      efonidipine has potent negative chronotropic and vasodilator effects but only a
      weak negative inotropic effect. In experimental animals and patients, reduction
      of blood pressure by the drug was accompanied by no or minimum reflex tachycardia
      leading to improvement of myocardial oxygen balance and maintenance of cardiac
      output. Efonidipine increased glomerular filtration rate without increasing
      intraglomerular pressure. By relaxing both the afferent and efferent arterioles,
      efonidipine markedly reduced proteinuria. Thus, efonidipine, an L- and T-type
      dual Ca(2+) channel blocker, appears to have an ideal profile as an
      antihypertensive and antianginal drug with organ-protective effects in the heart
      and kidney.

PMID- 12070537
TI  - Ethical considerations in the prevention and management of genetic disorders with
      special emphasis on religious considerations.
AB  - Genetic diseases include not only single gene disorders, but multifactorial,
      somatic cell genetic disorders, mitochondrial and even chromosomal. One in 4
      adults will suffer from a multifactorial or a somatic cell genetic disease. The
      common diseases in the community have a hereditary component namely diabetes
      mellitus, hypertension, ischemic heart diseases and many types of cancer. Even
      monogenic diseases which affect a small number of the newborns (2%-3%), have a
      greater impact on childhood diseases up to age 15 years. Therefore, it is
      imperative to scrutinize the available methods of prevention and management of
      genetic disorders, their ethical implications, and since east Mediterranean
      region is mainly occupied by Arabs and muslims, religious considerations become
      of paramount importance. Islam differs from many other religions in providing a
      complete code of life, which encompasses the secular with spiritual, the mundane
      with the celestial and hence forms the basis of the ethical, moral and even
      juridical attitudes and laws towards any problem or situation. Islamic teachings
      carry a great deal of instructions for health promotion and disease prevention
      including hereditary and genetic disorders. This review discusses how the Islamic
      teachings play an important role in the prevention and management of genetic
      disorders and the type of ethical implications involved in such management namely
      premarital medical examination, the question of consanguinity, the genetic
      counseling, the question of preimplantation diagnosis, the question of abortion
      and the offering of alternative ways of reproduction.

PMID- 12070538
TI  - Thyroid disease and pregnancy.
AB  - Several important issues must be considered when thyroid disorders occur during
      pregnancy. These include establishing the diagnosis (including an understanding
      of the effect of pregnancy and its hormonal changes on the immune system in
      general and the thyroid function in particular) treatment and uneventful maternal
      and neonatal outcome. The evaluation and treatment of women with thyroid disease
      during pregnancy parallels that of nonpregnant women and men, but presents unique
      problems. In addition some types of thyroid disorders occur only during pregnancy
      and the postpartum period. Pregnancy complicated by some thyroid disorders is
      associated with an increased rate of complications to the mother as well as to
      the fetus. This review will seek to discuss the diagnosis, management of
      different thyroid disorders during pregnancy and the postpartum period.

PMID- 12070539
TI  - Pediatric living-related liver transplantation in Saudi Arabia.
AB  - OBJECTIVE: The purpose of this paper is to report our experience of the first 29
      consecutive living-related liver transplants in pediatric recipients and to
      demonstrate the feasibility of living-related liver transplantation in the Arab
      World. The first living-related liver transplantation in the Kingdom of Saudi
      Arabia was performed in November 1998 by Bassas et al following an appropriate
      period of multi-disciplinary preparation. METHODS: This study was carried out at
      the Armed Forces Hospital, Riyadh, Kingdom of Saudi Arabia, during the period
      November 1998 through to October 2001. A review of the data of the transplanted
      children and adult donors was carried out. The data recorded for recipients
      included age, sex, patient's weight, preoperative diagnosis, intraoperative
      surgical complications, graft size and weight, medical and surgical postoperative
      complications, immunosuppression, rejection and overall survival rate. Data
      recorded for the donors included age, sex and any postoperative complications.
      RESULTS: The most frequent indication for living-related liver transplantation in
      our series was metabolic liver disease. Post-operative complications included
      biliary leaks in 10% (N=3), vascular occlusion in 13% (N=4), acute cellular
      rejection in 38% (N=11), positive cytomegalovirus PP65 antigen in 38% (N=11),
      wound infection in 3.4% (N=one), and systemic infections in 14% (N=4). One urgent
      retransplantation was necessary due to thrombosis of the hepatic artery. Patient
      and graft survival rates are 96% and 93%. One patient, treated for acute liver
      failure, died 2 months post-transplant. CONCLUSION: Our experience has shown
      pediatric living-related liver transplantation to be a success whilst alleviating
      the need for sending Saudi patients overseas for treatment and providing a
      solution to organ shortages for pediatric patients. In general, this endeavor has
      broadened the spectrum of our experience in surgery, anesthetics, intensive care
      and pediatrics.

PMID- 12070540
TI  - Job satisfaction of nurses in Ministry of Health Hospitals in Riyadh, Saudi
      Arabia.
AB  - OBJECTIVE: To examine the magnitude and determinants of job satisfaction in
      nurses working in Ministry of Health hospitals Riyadh, Kingdom of Saudi Arabia.
      METHODS: A modified version of the Minnesota Job Satisfaction Questionnaire is
      used to survey 500 nurses in 9 Ministry of Health hospitals in Riyadh, Kingdom of
      Saudi Arabia. Three hundred and sixty six nurses from different nationalities
      responded to the questionnaire (response rate 73%). Data analysis consisted of
      descriptive statistics, t-tests, one way-analysis of variance, correlation
      analysis, and regression analysis RESULTS: Overall job satisfaction was found to
      be moderate. The most important determinants of job satisfaction are:
      Recognition, technical aspects of supervision, work conditions, utilization of
      skills, pay, and job advancement. No differences were found in overall job
      satisfaction according to gender, age, income, nationality, or marital status.
      Differences were found according to educational level. Also, job satisfaction is
      positively correlated with years of experience. CONCLUSION: The study has
      important implications for the way that Ministry of Health hospitals are managed
      and for its policies regarding several aspects of human resources including
      efficient and effective use of nursing manpower.

PMID- 12070541
TI  - Are women at an increased risk of gestational thyrotoxicosis?
AB  - OBJECTIVE: To evaluate the relative importance of thyroid hormones and human
      chorionic gonadotropin in relation to the risk of gestational thyrotoxicosis in
      Saudi women living in Jeddah, Kingdom of Saudi Arabia. METHODS: A prospective
      study was conducted on Saudi healthy pregnant women (N=406) at 12-15 weeks of
      gestation and compared with healthy non-pregnant controls (N=200). Maternal serum
      levels of free thyroxine free triiodothyronine, thyrotropin, human chorionic
      gonadotropin and free b-human chorionic gonadotropin together with urinary iodine
      excretion were determined. Analysis of variance was used to examine differences
      among the groups for different variables and the Bonferroni criterion was used
      when significance tests were made. RESULTS: Pregnant women were classified into 2
      groups according to the lower limit of serum thyrotropin levels in non-pregnant
      euthyroid controls at >= 0.3 mIU/L (Group one) or < 0.30 mIU/L (Group 2).
      Suppressed levels of serum thyrotropin (< 0.30 mIU/L) were found in 11.1% of
      pregnant women which was accompanied by significant increases in free thyroxine
      (P<0.001), free triiodothyronine (P < 0.05), human chorionic gonadotropin
      (P<0.001) and b-human chorionic gonadotropin (P<0.001). A significant negative
      correlation between serum levels of thyrotropin and that of human chorionic
      gonadotropin (r=-0.381, P<0.001) was observed. The relative risk of having a
      serum thyrotropin level of < 0.30 mIU/L was 4.89 (P<0.001) for the pregnant women
      examined as compared with non-pregnant controls. Approximately 5.6% of the women
      examined exhibited biochemical evidence of thyrotoxicosis. CONCLUSION: The
      results of the present study show that Saudi pregnant women are at risk of
      developing biochemical evidence of thyrotoxicosis during early gestation, and
      thus, are likely to be at greater risk of clinically evident gestational
      thyrotoxicosis and hyperemesis gravidarum. Genetically determined differences in
      the synthesis or metabolism of human chorionic gonadotropin isoforms, or both may
      contribute to this increased risk.

PMID- 12070542
TI  - Disseminated intravascular coagulation and massive obstetric hemorrhage.
      Management dilemma.
AB  - OBJECTIVE: The objective of this retrospective study is to reflect on our
      experience on an optimal management for major postpartum hemorrhage, which would
      prevent the occurrence and complications of disseminated intravascular
      coagulation and minimize maternal mortality and morbidity. METHODS: Ten cases out
      of the 30,000 of total deliveries of severe obstetric hemorrhage associated with
      disseminated intravascular coagulation were studied. This study was carried out
      over a 7 year period, October 1988 through to September 1995, at the Obstetric
      Unit, King Khalid University Teaching Hospital, Riyadh, Kingdom of Saudi Arabia.
      RESULTS: All of the 10 women received packed red blood cells, 8 had fresh frozen
      plasma, and 6 received platelet transfusion. The 10 cases developed disseminated
      intravascular coagulation following medical and surgical management, all women
      needed hysterectomy, 4 subtotal, 6 total, and 5 women had relaparotomy and pelvic
      packing. Two had bladder injuries. There was no maternal death. CONCLUSION: An
      early resort to hysterectomy when conservative measures fail, will minimize
      maternal morbidity and mortality. In case of continuous bleeding after
      hysterectomy, pelvic packing proved to be effective.

PMID- 12070544
TI  - Restorative proctocolectomy with ileal reservoir.
AB  - OBJECTIVE: Restoractive proctocolectomy with ileal reservoir is a procedure that
      eliminates mucosal disease of the colon and rectum yet it preserves fecal
      continence. It has become the operation of choice for most patients with chronic
      ulcerative colitis and familial adenomatous polyposis. METHODS: The study was
      carried out at Baghdad Teaching Hospital, Medical City, Baghdad, Iraq, during the
      period January 1988 through to January 2001, we carried out 30 cases of
      restoractive proctocolectomy with ileal reservoir. At the beginning we used the S
      pouch (3 cases), then the J pouch (8 cases), finally we shifted to the extended J
      pouch (19 cases) with improved results. RESULTS: Our surgical technique and the
      pre-operative and post-operative care improved, with more cases of restorative
      proctocolectomy with ileal reservoir carried out in our center. This is
      associated with a good progress in the functional results and a decrease in the
      early and late complications of the procedure. CONCLUSION: Restorative
      proctocolectomy with ileal reservoir is a major surgical procedure with many
      early and late complications, but if it is carried out in expert hands with
      careful selection of the patients it will give good results.

PMID- 12070543
TI  - The effect of metformin plus clomiphene citrate on ovulation and pregnancy rates
      in clomiphene-resistant women with polycystic ovary syndrome.
AB  - OBJECTIVE: To study the effect of metformin in combination with clomiphene
      citrate, as compared with placebo plus clomiphene citrate, on the ovulation and
      pregnancy rates in clomiphene citrate-resistant women with polycystic ovary
      syndrome. METHODS: This study was carried out at King Hussein Medical Center,
      Amman, Jordan, during the period January 2001 through to July 2001. Twenty-eight
      clomiphene citrate-resistant polycystic ovary syndrome women were evaluated
      prospectively for 6 treatment cycles by receiving metformin, 850mg twice daily
      throughout the cycle along with 50 mg clomiphene citrate, starting on day 5-9 of
      the same cycle (N=16), or by taking placebo with clomiphene citrate (N=12).
      During cycles 2-6, clomiphene citrate was added with increments of 50mg (up to
      200 mg/day) for both groups. Progesterone level on day 21 and 28 >5ng/dl was
      indicative of ovulation. RESULTS: A statistically significant increase in the
      rates of ovulation (68.6% versus 25%, p<0.05) and pregnancy (56.3% versus 16.6%,
      p<0.05) were observed in the metformin-clomiphene citrate group as compared with
      the placebo-clomiphene citrate controls. Insignificant increase in the rate of
      ovarian hyperstimulation was noted in the placebo-clomiphene citrate group.
      CONCLUSION: Metformin-clomiphene citrate regimen in resistant-clomiphene citrate
      polycystic ovary syndrome women significantly increases the ovulation and
      pregnancy rates, and decreases the occurrence of ovarian hyperstimulation
      syndrome.

PMID- 12070545
TI  - Rate and risk factors of surgical site infections with antibiotic prophylaxis.
AB  - OBJECTIVE: This study is aimed at determining the incidence of surgical site
      infections, with antibiotic use. Furthermore, to correlate infection with type of
      operations, length of intervention, number of stitches, pre-operative
      hospitalization, age and sex of the patient. METHODS: All Yemeni patients (N=601)
      who underwent surgical intervention, with preoperative antibiotic prophylaxis, at
      Al-Kuwait University Hospital, Sana'a, Republic of Yemen, during 1st August 2000
      through to 30th November 2000 were followed up until stitch removal or discharge.
      Data was registered in a spreadsheet and processed statistically by statistical
      package for social sciences 10.0. RESULTS: Overall incidence of surgical site
      infections was 2.2%, 0.5% in clean operation, 2.8% in clean contaminated, 9.1% in
      contaminated and 2.3% in dirty operations. Surgical site infections were found
      positively correlated with duration of operation (P=0.015) and number of stitches
      (P=0.017), but insignificantly associated with sex, age, type of operation and
      pre-operative hospitalization. CONCLUSION: In conclusion, surgical site
      infections, with antibiotic use, were found low. Higher number of stitches and
      longer duration of operation were the risk factors.

PMID- 12070546
TI  - Etiology of chronic diarrhea.
AB  - OBJECTIVE: The aim is to find the common causes of chronic diarrhea in our
      hospital, and to find out the most useful methods for diagnosis. METHODS: This
      study was carried out in the medical ward at Al-Yarmouk Teaching Hospital,
      Baghdad, Iraq, during the period January 1999 through to August 2000. Fifty
      inpatients with diarrhea for 4 weeks or more were evaluated by history, physical
      examination and investigations which included endoscopy with biopsy. RESULTS: The
      first cause of chronic diarrhea was ulcerative colitis (28%), the next was celiac
      disease (20%), followed equally by microscopical colitis (12%) and functional
      diarrhea (12%), amebiasis was the 5th cause (10%), followed by carcinoma of the
      colon (6%), Crohn's disease (2%), diabetic diarrhea (2%) and thyrotoxicosis (2%).
      Endoscopy (esophagoduodenoscopy, sigmoidoscopy and colonoscopy) with biopsy was
      the most useful method to diagnose >70% of the cases as ulcerative colitis,
      celiac disease, microscopic colitis, carcinoma of the colon and Crohn's disease.
      CONCLUSION: This study revealed the importance of history taking, physical
      examination, and judious and sequential use of investigations especially
      endoscopic procedures to discover the cause of chronic diarrhea. Chronic bloody
      diarrhea should raise the high possibility of ulcerative colitis. A considerable
      number of patients with chronic diarrhea in our study were discovered to have
      microscopical colitis.

PMID- 12070547
TI  - Sero-response to measles-mumps-rubella vaccine campaign in Saudi Arabia.
AB  - OBJECTIVE: To evaluate the measles-mumps-rubella vaccine campaign targeting
      primary school children in the Kingdom of Saudi Arabia during the months of
      January and February 2000. METHODS: Pre and post measles-mumps-rubella vaccine
      blood samples were collected from 54 children from the first grade and 96
      children from the 6th grade. Antibodies against measles, mumps and rubella were
      assayed using enzyme immunoassay and a backup test of plaque neutralization test.
      This assay was carried out at the Reference Center, Koch Institute, Berlin,
      Germany. RESULTS: When the backup test results were added, 96%-98% of children
      had protection level against measles before the campaign. It is interesting to
      notice that pre-vaccination measles mean titer and positivity rate with enzyme
      linked immunoassay in the first grade were significantly lower than the 6th
      grade. One hundred percent and 96.8% were positive for rubella antibody before
      the campaign, in the first and 6th grades. Seventy-seven percent and 67% were
      positive for mumps before the campaign, in the first and 6th grade. After the
      measles-mumps-rubella vaccine campaign, protection rate reached 100% for the 3
      antigens with a statistically significant boosting effect and increase in
      geometric mean of the titre. CONCLUSION: Measles-mumps-rubella vaccine campaign
      was effective in increasing protective levels and boosting antibodies against the
      3 targeted diseases which can prevent epidemics in the primary schools.

PMID- 12070548
TI  - Malaria parasitemia during delivery.
AB  - OBJECTIVE: The aim of this study is to investigate the impact of plasmodium
      falciparum infection in parturient women in Central Sudan where malaria
      transmission is mesoendemic. The purpose of this paper is to find out the
      prevalence of malaria parasitemia and the risk of anemia among parturient women
      and to suggest appropriate strategies to lower their prevalence rates. METHODS:
      This prospective study was conducted at Medani Teaching Hospital, Sudan, a
      tertiary regional referral center, during the period January 1997 through to
      December 1997. All cases were admitted during labor to the delivery room and were
      clinically suspected to have malaria. History, examination and investigations
      were carried out on all patients. RESULTS: The total number of patients enrolled
      in this study was 550, amounting to 14.9% of all women (N=3,687) who delivered
      during the study period. The prevalence of malaria parasitemia was 58.9% (N=550)
      while prevalence of anemia (defined as hemoglobulin <9.0 g/dl) was 24.1%. The
      mean hemoglobulin levels in patients with positive and negative malaria
      parasitemia was 9.72   1.62 and 9.85   1.60 g/dl. Statistically the difference in
      the mean hemoglobulin level was not significant, t=0.879, (P>0.05). A significant
      negative correlation between parasite count in maternal blood and hemoglobulin
      level of the mother, was observed, where r=-0.121 (P=0.032). Out of 17 (3.3%)
      patients who had used chloroquine tablets for prophylaxis, 11 patients still had
      positive parasitemia. Although there was a higher parasite count in those 11
      patients, statistically the difference was not significance where P> 0.05.
      CONCLUSION: The study documents a high prevalence of malaria parasitemia and
      anemia among the parturient women in Central Sudan. There were 533 pregnant women
      (97%) who did not use chloroquine tablets as chemoprophylaxis and 17 (3%) had
      prophylaxis. Eleven of the later (N=17) had positive parasitemia. In view of the
      high prevalence of parasitemia and anemia, and although the sample of patients
      who used chloroquine tablets for prophylaxis and had positive parasitemia is
      small (17 out of 550), a wide scale prophylaxis placebo-controlled trial is
      recommended to test the impact of prophylactic drugs in pregnancy and to measure
      the effect on the mother, and the neonate. The drug that proves to be effective
      as a prophylactic, should be an integral part of ante-natal care along with iron
      and folic acid as anti-anemic therapy. Moreover, prompt treatment of malaria
      infection with the appropriate anti-malarial drug, spray of insecticides and the
      use of insecticide-impregnated bed-nets and curtains for preventing malaria are
      recommended.

PMID- 12070549
TI  - Treatment of thoracolumbar fractures.
AB  - OBJECTIVE: To study the outcome of patients with thoracolumbar fracture treated
      surgically or conservatively at the Armed Forces Hospital, Riyadh, Kingdom of
      Saudi Arabia, between the year 1989 through to 1999. METHODS: The medical and
      surgical record of all patients diagnosed as having thoracolumbar fracture
      (thoracic 10-lumbar 12) between the years 1989 to 1999 were reviewed. The
      parameter studies included the personal patient data, type of fracture, mechanism
      and cause of injury and neurological affection. For the outcome, the method of
      treatment and recovery from neurological deficit, return to pre-injury activity
      and work as well as complications were noted. RESULTS: One hundred patients were
      treated for thoracolumbar fracture. Seventy two percent were related to motor
      vehicle accident, 37% had neurological deficit, 19 of them had complete lesion.
      Thoracic 12 Lumbar 1 constituted 63% of injury level. Forty-four patients were
      treated surgically whereas 56 had conservative treatment. At follow up, 17
      patients had complete recovery from neurological deficit while 6 had partial
      recovery and 14 had no recovery at all. No major complication has occurred due to
      method of treatment in both groups. CONCLUSION: Treatment of thoracolumbar
      fracture was carried out using both surgical and conservative methods. In our
      view, surgical treatment is indicated in cases of instability or removal of
      retropulsive fragment if there is neurological deficit or to correct deformity.
      For other cases conservative treatment was selected and gave satisfactory
      results.

PMID- 12070550
TI  - Surgically treated transitional cell carcinomas of the bladder. The role of
      radical surgery.
AB  - OBJECTIVE: To assess the treatment outcome and differentiate between the
      individual behavior of the tumor stages that were studied (Ta, T1, and T2a) with
      special reference to T2a tumors. METHODS: This study was carried out at Al
      Rasheed Military Hospital, Baghdad, Iraq, during a 12 year period. Fifty-six
      patients with Ta, T1, and T2a (superficial invasion of muscularis propria)
      transitional cell carcinomas of the bladder, have been retrospectively analyzed.
      They were treated surgically with either transurethral of the bladder tumor
      (N=45) or radical surgery (N=11). Tumors with frequent recurrences or mulifocal
      or extending to the ureter or vesical outlet were treated with radical surgery.
      No adjuvant intraveiscal chemotherapy or bacillus calmette-guerin therapy was
      practiced. RESULTS: All Ta tumors were controlled by transurethral of the bladder
      tumor treatment. Seventy-five percent of T1 tumors were controlled by
      transurethral of the bladder treatment and 25% qualified for radical surgery
      according to our criteria. Sixty percent of T2a tumors were controlled by
      transurethral of the bladder treatment and 40% warranted radical surgery. No
      stage progression occurred in Ta and T1 lesions, but 27% of T2a lesions
      (superficial invasion of muscularis propria) progressed to T2b (deep invasion of
      muscularis propria). All grade 2a lesions of all stages under study were
      controlled by transurethral of the bladder treatment. Of 6 patients with T2a
      grades 2b and 3 tumors, 5 patients (83%) qualified for radical surgery. No
      distant metastasis occurred during the observation period, which ranged from 4
      months to 12 years (mean 51 months). Seventy-five percent of all patients, 78% of
      the transurethral of the bladder treatment group and 64% of the radical surgery
      group are alive and free of disease for 5 years or more. CONCLUSION: Radical
      surgery is indicated for T1 and T2a bladder carcinomas if they were multifocal,
      or extending to the ureter or the vesical outlet or frequently recurring within
      the first year, specially if they were T1 tumors of grade 3 or T2a tumors of
      grades 2b and 3. Transurethral resection is justifiable for grades 1 and 2a, low
      risk T2a tumors.

PMID- 12070551
TI  - BRCA1 and BRCA2 mutations in breast cancer patients from Saudi Arabia.
AB  - OBJECTIVE: The aim of this pilot study was to screen the major segments of the
      BRCA1 and BRCA2 genes for disease-associated mutations in Arab and Asian women
      with breast cancer from the Kingdom of Saudi Arabia. METHODS: Deoxyribonucleic
      acid samples from 29 Arab women and 11 Asian women, with unilateral breast cancer
      were investigated for BRCA1 and BRCA2 mutations. For this purpose single strand
      conformation polymorphism and direct nucleotide sequencing techniques were
      employed. This study was carried out at King Fahad Hospital of the University, Al
      Khobar, Kingdom of Saudi Arabia, during the time frame March 2000 through to
      August 2001. RESULTS: One novel BRCA2 truncating mutation, the frame-shift
      mutation 2482delGACT, was uncovered in an Arab patient of Palestinian descent.
      This mutation is a 4-nucleotide deletion that creates a stop signal at codon 770
      of the BRCA2 transcript. The BRCA1 disease-associated mutation Arg841Trp was
      detected in another Arab patient from Egypt. The clinical presentation in the 2
      heterozygous carriers of these 2 mutations is described here. In addition the
      unclassified BRCA1 variant Phe486Leu combined with Asn550His, and the
      unclassified BRCA2 variant Asp1420Tyr, were identified in Arab patients. Five
      BRCA1 polymorphisms and 6 BRCA2 polymorphisms were detected at different allele
      frequencies in both mutation carriers and patients with normal genotype.
      CONCLUSION: We conclude that BRCA1 and BRCA2 mutations are likely to contribute
      to the pathogenesis of familial breast cancer in female patients from the Kingdom
      of Saudi Arabia.

PMID- 12070552
TI  - Do antibiotics decrease post-tonsillectomy morbidity?
AB  - OBJECTIVE: A tonsillectomy audit was carried out and compared with other studies,
      to emphasize the role of antibiotics. METHODS: This study was carried out at
      North West Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia, during the year
      January 1999 through to December 1999. This is a retrospective study of patients
      who had tonsillectomy with or with adenoidectomy, the topics audited included
      indication for surgery, grade of surgeon, method of surgery, length of hospital
      stay, complications and the use of postoperative antibiotics. RESULTS: A total of
      185 patients underwent tonsillectomy with or without adenoidectomy. The patients
      age ranged between 2 years to 53 years and the majority were children. In our
      audit we found no difference with regard to grade of surgeons, method of
      hemostasis in the outcome of surgery. Moreover, postoperative antibiotics had no
      role in pain control, postoperative fever, secondary hemorrhage or reduction in
      hospital stay. The administration of analgesics on the basis of, as required, had
      poor pain control. CONCLUSION: Post tonsillectomy antibiotics did not prove to
      have a role in minimizing postoperative morbidity. Moreover, analgesics given on
      the basis of as required had a limited value.

PMID- 12070553
TI  - Point prevalence of type B tympanogram in children.
AB  - OBJECTIVE: Otitis media with effusion is a common disease; it is primarily a
      disease of children. Otitis media with effusion was found as the most common
      cause of hearing impairment among children. The prevalence varied in different
      populations. Using otoscopy and tympanometry usually gives a valuable indication
      of the presence of otitis media with effusion. The aim of this study is to
      determine the point prevalence of type B tympanogram as a diagnostic and
      indication of the presence of otitis media with effusion. METHODS: This study was
      carried out during the period September 1997 through to May 2000. The study
      population consisted of 9540 children aged one year to 12 years from the 4
      provinces of the country. Otoscopic examination and audiologic assessment were
      carried out using Grason Stadler Incorporation 30-33. The tympanograms were
      divided into A, B, C one, and C2 groups. RESULTS: The point prevalence rate of
      type B tympanograms among children was 8.2%. The prevalence of otitis media with
      effusion was 7.5% CONCLUSION: This study indicates that tympanogram has a
      significant role in otis media effusion.

PMID- 12070554
TI  - Retroperitoneal fibrosis. Demographic, clinical and pathological findings.
AB  - OBJECTIVE: To describe the clinical characteristics of patients with
      retroperitoneal fibrosis including the etiopathogenesis, clinical features,
      diagnostic criteria and effective treatment of the disease. METHODS: This study
      was carried out at Princess Basma Teaching Hospital, Irbid, Jordan, during the
      year 2001. Records of 15 patients with retroperitoneal fibrosis were
      retrospectively reviewed. Demographic, clinical and pathological criteria was
      evaluated and analyzed. RESULTS: From 1990 to 2000, there were 15 patients seen
      with retroperitoneal fibrosis (10 men and 5 women; the mean age was 55.8 years,
      ranging between 39 years to 75 years). Nine cases were idiopathic and 6 were
      secondary. Risk factors of the idiopathic group were cigarette smoking (6
      patients) and arterial hypertension (4 patients). Etiologic factors of the
      secondary group were aortic abdominal aneurysm (3 cases including one following
      abdominal aortic surgery), radiation therapy for seminoma (one case), ergot
      derivative treatment (one case), retroperitoneal non-Hodgkin lymphoma (one case).
      Main presentations were abdominal or back pain, or both. Treatment performed was
      medical in 5 cases, medical and endourological in 3 cases and 7 patients received
      surgical treatment. Medical treatment induced remission in 3 patients, while
      endourological and surgical treatment resulted in complete recovery in 9 patients
      (including the 2 patients who failed medical treatment). In the remaining 3
      patients treatment failed and the disease relapsed. CONCLUSION: Awareness of this
      rare disorder is important to prevent misdiagnosis. Retroperitoneal fibrosis
      remains a difficult therapeutic challenge. Aggressive medical, endourological or
      surgical treatment, or both are equally good modalities for its treatment.

PMID- 12070555
TI  - An audit of oxygen therapy on the medical ward in 2 different hospitals in
      Central Saudi Arabia.
AB  - OBJECTIVE: To study the use of oxygen therapy on the medical wards in 2 hospitals
      in Riyadh, Kingdom of Saudi Arabia. One was academic, King Khalid University
      Hospital and the other a community hospital, Riyadh Medical Complex. METHODS:
      This study was carried out over a one year period, 6 April 2000 through to 6
      April 2001. Oxygen saturation was measured randomly by pulse oximetry in patients
      receiving oxygen therapy. Charts of the patients were inspected for relevant
      information related to oxygen therapy, including indications, dose, monitoring
      and documentation of the order. If oxygen saturation was >97% oxygen flow was
      reduced to maintain oxygen saturation between 92% and 94%. The potential savings
      by such reduction were calculated. RESULTS: A total of 108 patients were studied.
      The most frequent indications for oxygen therapy were hypoxemia and dyspnea.
      Arterial oxygen tension before starting oxygen was carried out for 78 patients
      (72.2%) and showed that the majority (60 patients, 76.9%) were hypoxemic arterial
      oxygen tension <= 65 mm Hg). The last documented arterial oxygen tension values
      after initiating oxygen were found in 79 patients (73.1%) and these were carried
      out at mean interval of 111 hours (range one-1200) before our assessment. Most
      patients (32 patients, 40.5%) had excessive values (>85 mmHg), 24 patients
      (30.4%) were hypoxemic (arterial oxygen tension <=65 mmHg) and only 23 patients
      (29.1%) had acceptable values (arterial oxygen tension > 65-85 mmHg). Our
      measurements also showed that arterial oxygen tension was excessive (>97%) in 59
      patients (54.6%), adequate (>=92%-97%) in 44 patients (40.7%), and only a
      minority (5 patients, 4.6%) were hypoxemic (<92%). Oxygen dose could be reduced
      in 31 patients (28.7%) by a mean of 42% (range 18%-66%) and stopped in 38
      patients (35%) while maintaining aterial oxygen tension between 92%-94%. Errors
      in oxygen prescription were more apparent in the non-academic setting (P<0.05%).
      CONCLUSION: Oxygen prescription was sub-optimal in both the academic and non
      academic setting. The study highlights the need to adopt and evaluate cost
      effective measures such as oxygen titration protocols using pulse oximetry, and
      physician education programs.

PMID- 12070556
TI  - Prevalence of mental illness among Saudi adult primary-care patients in Central
      Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of mental illness morbidity among Saudi
      adult primary care patients from Al-Kharj, Kingdom of Saudi Arabia. METHODS: This
      is a cross-sectional epidemiological study of the prevalence of mental illness
      morbidity in a randomly selected sample of 609 Saudi adult patients, aged from 15
      years to 65 years who attended Family and Community Medicine Clinic, Armed Forces
      Hospital, Al-Kharj, Kingdom of Saudi Arabia, from July 2000 to November 2000. The
      Rahim Anxiety-Depression Scale was used in the evaluation. RESULTS: In this
      study, 609 Saudi patients were screened. Their mean age   standard deviation was
      33.72   13.39. Of these, 46.6% were men and 53.4% were women. The prevalence of
      the minor mental illness morbidity was 18.2%, (30.5% when the sub-threshold
      mental illness are included). It was significantly higher in women (22.2%) than
      men (13.7%) with p-value=0.0073. The prevalence rate was high in the younger age
      group, (p<0.0001). In patients aged 15 years to 29 years it was 23.2%, and in
      those aged between 30 years and 44 years it was 17.8%, whereas, in patients aged
      45 years to 65 years the prevalence was 7.1%. Also, the rate was high in
      divorcees (40%) and widows (43.8%). The prevalence rate in patients with diabetes
      mellitus was 16% (p=0.562), with hypertension, 22.2% (p=0.303), and with
      bronchial asthma, 28.3% (p=0.008). Multiple logistic regression analysis showed
      that age, gender and bronchial asthma were associated with mental illness.
      CONCLUSION: Our study shows that one 3rd of primary health care patients have
      mental illness. Due to the high prevalence of mental illnesses among primary
      health care clinic attendants and screening for such problems by using Rahim
      Anxiety-Depression scale could be time consuming, exploring the psychiatric
      dimension and effect of diseases should be included during any consultation.

PMID- 12070558
TI  - Iatrogenic perforation of the esophagus.
AB  - Iatrogenic perforation of the esophagus occurs rarely, and is most frequently
      seen in preterm and low birth weight infants. This is a report of 2 cases of
      iatrogenic perforation of the esophagus, outlining aspects of diagnosis and
      management.

PMID- 12070557
TI  - A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin
      pharmacodynamics and kinetics in the treatment of patients with chronic ischemic
      heart failure.
AB  - OBJECTIVE: To evaluate the effect of an arteriolar dilator (diltiazem
      hydrochloride) versus a venodilator (isosorbide dinitrate) on digoxin kinetics
      and to estimate the efficacy and tolerability of these vasodilators when combined
      with digoxin for 10 days therapy in patients with congestive heart failure
      secondary to ischemic heart disease. METHODS: A double blind randomized cross
      over study was carried out to investigate the effect of an arteriolar dilator
      (diltiazem hydrochloride 180 mg/day orally) versus a venodilator (isosorbide
      dinitrate 30 mg/day orally) on digoxin kinetics (0.25 mg/day orally), after 10
      days therapy in patients with heart failure due to ischemic heart disease. Also,
      the effect of these drugs on blood pressure, heart rate, renal functions and
      serum electrolytes, and their efficacy and tolerability in combination with
      digoxin were studied. This study was carried out in the Department of Medicine,
      Main Alexandria University Hospital, Alexandria, Egypt, during the period May
      1999 through to May 2000. RESULTS: Diltiazem caused a significant increase in
      digoxin maximum serum concentration without significant change in time to reach
      maximum concentration and the apparent volume of distribution. The total digoxin
      clearance was significantly reduced and the elimination half life was prolonged.
      Subsequently the area under time-concentration curve and the steady-state digoxin
      level were increased, but were still within therapeutic margin. On the other hand
      isosorbide dinitrate significantly increased digoxin maximum serum concentration
      but without change in the other digoxin pharmacokinetic parameters. Isosorbide
      dinitrate, but not diltiazem, caused significant reduction in supine and standing
      blood pressure, while both drugs did not significantly alter pulse rate, renal
      functions, serum sodium potassium and electrocardiographic pattern. CONCLUSION:
      Patients who received diltiazem displayed a mean 51% increase in the area under
      the plasma concentration-time curve, 50% increase in mean steady state serum
      digoxin concentration, and 37% increase in peak serum digoxin concentration.
      While patients who received isosorbide dinitrate showed only a 15% increase in
      digoxin maximum serum concentration and no statistically significant change in
      mean steady state digoxin concentration or area under the plasma concentration
      time curve. The elimination half life during the diltiazem phase was prolonged by
      29% while there was no significant change with isosorbide dinitrate. Netiher
      diltiazem or isosorbide dinitrate significantly altered the time to reach maximum
      serum digoxin concentration. The addition of a vasodilator such as, diltiazem or
      isosorbid dinitrate to digoxin could significantly improve the symptoms and signs
      of heart failure compared to digoxin alone. They were well tolerated and without
      fear of electrolyte imbalance which potentiate digoxin toxicity.

PMID- 12070559
TI  - Acute pancreatitis complicated by spontaneous unilateral adrenal hemorrhage.
AB  - A 52-year-old lady with a history of hypertension, dilated cardiomyopathy and
      diabetes mellitus type 2, presented with severe upper abdominal pain and vomiting
      of 4 hours duration. Acute pancreatitis was diagnosed based on high serum amylase
      and an abdominal computerized tomography scan. On the 3rd day she developed
      fever, increasing abdominal pain and shortness of breath. A repeated computerized
      tomography scan showed severe pancreatic necrosis and right adrenal hemorrhage.

PMID- 12070561
TI  - Membranoproliferative glomerulonephritis due to Hepatitis C in renal allograft.
AB  - Membranoproliferative glomerulonephritis type 1 is an etiologically divergent
      disorder. Hepatitis C with or without cryoglobulinemia is considered one of the
      principal causes of de novo and post transplant membranoproliferative
      glomerulonephritis type 1. A 49-year-old male who underwent renal allograft for
      end stage renal disease developed proteinuria and positive hepatitis C serology
      during the post-transplant period. This was associated with moderate hepatic
      dysfunction, which necessitated both liver and renal biopsies. Features of both
      chronic active hepatitis and membranoproliferative glomerulonephritis type 1 were
      seen as a result of histological examination of both liver and renal biopsies.
      Ultra structural studies showing mesangial and membranous deposits which are
      characteristic of membranoproliferative glomerulonephritis have been observed.
      The case is reported with a review of pertinent medical literature.

PMID- 12070560
TI  - Malignant familial long QT syndrome.
AB  - We report a family with congenital long QT syndrome, an inherited disorder of
      myocardial repolarization in which affected individuals have prolongation of
      corrected QT interval on the electrocardiogram and a tendency to develop
      ventricular arrhythmia, leading to syncope, convulsion or sudden death. Our
      family is characterized by several affected members (11/16), early onset of
      symptoms, malignant course prior to diagnosis and good response to beta-blocker
      therapy. The genetic basis of long QT syndrome has been traced to defective
      proteins encoding cardiac ion channels. Diagnosis is based on an unexplained
      prolongation of QT interval >0.45 second in the presence of suggestive symptoms
      or evidence, or both of a familial pattern. Beta-adrenergic blocker therapy gives
      symptomatic relief in 80%-85% of patients. Precipitating factors like vigorous
      exercise especially swimming and exposure to significant emotional or auditory
      stimuli should be avoided. Occasional patients require in addition, a demand
      cardiac pacemaker, left cardiac sympathectomy or an implantable cardioverter
      defibrillator, or both. Regular follow up is mandatory even after subsidence of
      symptoms.

PMID- 12070562
TI  - Presacral fibroma in a young laborer presenting with chronic lumbago.
AB  - A 24-year-old patient had a long history of low backache. After examination he
      was found to have a presacral mass grossly displacing the rectum anteriorly.
      Surgical exploration revealed a large rounded mass (20x17x10cm) occupying the
      presacral space and adherent to the sacral promontory. The mass was totally
      excised. The histology was a benign fibroma. The patient persued an excellent
      post-operative course and has remained symptom free for one year now.

PMID- 12070563
TI  - Researcher's guide to health statistics.

PMID- 12070564
TI  - Controversial aspects in the management of perforated appendicitis in children.

PMID- 12070565
TI  - A survey of the reasons for vasectomy refusal in couples who have chosen
      tubectomy as their contraceptive method.

PMID- 12070566
TI  - Cecal vascule. An overlooked mechanism of cecal volvulus.

PMID- 12070567
TI  - Current trends in hormone replacement therapy.
AB  - As life span increases, more and more women live longer after the menopause, and
      see its long-term consequences. The menopause and climacteric have major
      consequences for the well being of most women, resulting in a variety of symptoms
      including vasomotor, psychological, sexual symptoms and increased risk of
      osteoporosis and atherosclerosis. Prevention of osteoporosis and reduction in
      cardiovascular risks are the long-term goals of post-menopausal hormone
      replacement therapy. Post-menopausal women who receive hormone replacement
      therapy have approximately half of the rate of coronary artery disease compared
      to those who do not take it. Similarly, estrogen replacement alone for 5 years
      results in 50% reduction in the risk of overall fracture and is a major factor in
      the prevention and management of osteoporosis. A wide range of estrogen
      preparations is available for administration by various routes. The choice
      depends on indications, side effects and convenience. Oral estrogen is the most
      commonly used preparation followed by transdermal preparation. Controversy still
      exists over the efficacy and safety of hormone replacement therapy among both the
      medical and lay authorities. There is overwhelming evidence that hormone
      replacement therapy improves the quality of life and reduces the morbidity and
      mortality by reversing the metabolic and pathological changes induced by the
      menopause. The benefits of hormone replacement therapy out weigh any increased
      risk of venous thromboembolism or breast, ovarian and endometrial cancers.

PMID- 12070568
TI  - Extrapulmonary tuberculosis, epidemiology and patterns in Saudi Arabia.
AB  - Annual incidence rates of extrapulmonary tuberculosis have been increasing over
      the last few years in the Kingdom of Saudi Arabia. True rates may even be higher
      due to incomplete reporting. Diagnosis of this condition requires high clinical
      suspicion, special diagnostic procedures, special staining, and culture media for
      acid fast bacilli. Delayed diagnosis results in increasing morbidity, mortality,
      and cost to the health care system. Particularly in areas of high endemicity of
      Mycobacterium tuberculosis, clinicians should be aware of the various forms of
      extrapulmonary tuberculosis. The available epidemiology and patterns of various
      forms of extrapulmonary tuberculosis in the Kingdom of Saudi Arabia are presented
      in this review.

PMID- 12070569
TI  - The status of cadaveric organ donation for liver transplantation in Saudi Arabia.
AB  - OBJECTIVE: Over the past 2 decades, liver transplantation has became the standard
      treatment of end stage liver disease. Organ shortage has been the main hindrance
      against the progress of liver transplantation in the Kingdom of Saudi Arabia.
      This paper reports the status of organ donation for liver transplantation in the
      Kingdom of Saudi Arabia and highlights the problems and the suggested solutions
      in relation to organ shortage. METHODS: All donors reported to the liver
      transplant program at the King Fahad National Guard Hospital, Riyadh, Kingdom of
      Saudi Arabia, from the Saudi Center of Organ Transplantation from January 1994
      through to June 1998 was retrospectively analyzed. Clinical and laboratory data
      were evaluated to decide on the suitability of organs for liver transplantation.
      RESULTS: Out of 216 donor offers only 100 were harvested and utilized (46%). Out
      of the remaining 116, 8 donors were declined based on bad clinical and laboratory
      data and the remaining 36 donors' livers were harvested but not used based on
      abnormal liver histology. This resulted in discarding more than 50% of the
      offered donors. The main reasons were related to poor donor maintenance and
      logistical delay. CONCLUSION: The number and quality of organs offered for liver
      transplantation in the Kingdom of Saudi Arabia over the past 6 years has been
      deteriorating with a negative impact on the liver transplant programs. Adopting
      new strategies is required to support the donor program in the Kingdom of Saudi
      Arabia. It is proposed that establishment of donor promotion offices in major
      hospitals can change the dismal picture of organ donation in the Kingdom of Saudi
      Arabia even at the current consent rate by better utilization of the available
      donors.

PMID- 12070571
TI  - The effect of magneto-treated blood autotransfusion on central hemodynamic values
      and cerebral circulation in patients with essential hypertension.
AB  - OBJECTIVE: The work was carried out to study the effect of magneto-treated blood
      autotransfusion on the values of central and cerebral hemodynamics in patients
      with essential hypertension. METHODS: Sixty-six patients with stage II essential
      hypertension aged 31-60 years who underwent magneto-treated blood autotransfusion
      were evaluated and treated, at the Cardiology Department, Hospital of Ministry of
      Internal Affairs of the Azerbaijan Republic, over a period of 8 years. The
      diagnosis was based on clinical examination and generally accepted criteria of
      essential hypertension stages proposed in 1978 by the World Health Organization.
      RESULTS: Sixty-six patients with stage II essential hypertension with stable drop
      in blood pressure, simultaneously showed a positive clinical effect. Central
      hemodynamic changes in the process of magneto-treated blood autotransfusion were
      different and depended on the initial state of circulation. High clinical effect
      showed the patients with hyperkinetic type of hemodynamics. Their blood pressure
      were significantly lower than the patients with hypokinetic type of circulation.
      CONCLUSION: Rheoencephalographic study demonstrated that magneto-treated blood
      autotransfusion possessed insignificant effect on cerebral hemodynamics, mainly
      expressed by the reduction of arterial blood flow tension in the patients with
      hypokinetic type of hemodynamics.

PMID- 12070570
TI  - Trends in the management of blunt liver trauma.
AB  - OBJECTIVE: Blunt liver trauma management has changed over the last 2 decades to
      include non-operative management as one of the standard approaches, particularly
      to those with minor liver injury. We reviewed the experience at a non-trauma
      hospital to identify trends in methods of evaluation and management of blunt
      liver trauma and discuss its outcome. METHODS: Medical records of 21 patients who
      sustained blunt liver trauma between June 1992 and July 1999 were retrospectively
      reviewed at King Fahad Military Medical Complex, Dhahran, Kingdom of Saudi
      Arabia. RESULTS: Thirty-three percent received non-operative management and
      recovered without complications. The rest received an operative management but in
      comparison had more severe liver injury scales, higher incidence of associated
      injuries, significantly greater blood transfusion requirements, longer hospital
      stay and a mortality rate of 67%. CONCLUSION: Non-operative management of blunt
      liver trauma is a valid effective option. It requires less blood transfusion and
      shorter hospital stay and is associated with a low complication rate. Severe
      liver injury can be associated with high mortality. Outcome can be significantly
      affected by both the severity of liver trauma and associated injuries
      particularly severe head injury. Management of the severely injured is expected
      to have a better outcome in a trauma centre.

PMID- 12070572
TI  - Efficacy and tolerability of valsartan in patients with mild to moderate
      essential hypertension.
AB  - OBJECTIVE: To assess the efficacy of valsartan in a different ethnic population
      than that studied in international trials. Also to compare the adverse
      experiences reported in this trial with those reported internationally. METHODS:
      A total of 2940 patients with newly diagnosed or established uncomplicated mild
      to-moderate essential hypertension participated in this open-label study. Each
      participating investigator was asked to enrol 12 patients, 10 on valsartan and 2,
      serving as controls, on any other anti-hypertensive. The control group included
      patients of similar clinical setting, disease severity, and overall health
      profile using alternative anti-hypertensive treatments was enrolled for tracking
      of patients receiving any anti-hypertensive other than valsartan. RESULTS: Both
      valsartan and the control medications showed a clear-cut antihypertensive effect.
      However, valsartan showed significantly better antihypertensive efficacy compared
      to the control group at the final visit. Twenty-four percent of patients in the
      control group compared to 3.9% in the valsartan group reported adverse
      experiences (P<0.001). Dizziness and headache were the most common treatment
      related reported adverse experiences. Dry cough was more commonly reported in the
      control group compared to patients in the valsartan group. CONCLUSION: Data from
      this study suggest, in line with data from international clinical studies, that
      valsartan is well tolerated and is at least as effective as other commonly used
      medications in the treatment of patients with mild to moderate hypertension.

PMID- 12070573
TI  - A pilot study of cardiac troponin I in patients with acute myocardial infarction
      and unstable angina.
AB  - OBJECTIVE: To assess the value of cardiac troponin I in the initial management of
      acute myocardial infarction and unstable angina, as well as the concordance
      between creatine phosphokinase-cardiac isoenzyme and cardiac troponin I. METHODS:
      We reviewed retrospectively the charts of 32 patients with acute myocardial
      infarction or unstable angina admitted to the Intensive Care Unit from the
      Emergency Room of King Khalid Military City Hospital, Hafar-Al-Batin, Kingdom of
      Saudi Arabia from April 1998 to September 2000. The time of admission to the
      intensive care unit, which corresponds to the beginning of thrombolytic therapy,
      the time when cardiac enzymes (creatine phosphokinase-cardiac isoenzyme and
      cardiac troponin I) are available as well as number of cardiac troponin I
      determinations before obtaining a significant positive result (>2ng/ml) and the
      delay between admission and the first significant positive result of cardiac
      troponin I, were evaluated. RESULTS: Sixteen patients had confirmed acute
      myocardial infarction based on the association of typical chest pain,
      electrocardiographic findings with ST segment elevation and significant increase
      of the ratio creatine phosphokinase-cardiac isoenzyme/creatine phosphokinase >
      10%. Sixteen patients had unstable angina and out of the 16 patients (81.25%)
      with acute myocardial infarction, 13 received thrombolytic therapy which was
      initiated on the basis of typical clinical history and electrocardiographic
      features, before the availability of cardiac enzymes. Troponin I was available in
      only 13 cases. The number of tests performed in these patients was 32. The first
      positive result of cardiac troponin I was available within a mean time of 16.66  
      20.8 hours from admission. The number of negative tests performed before
      obtaining a frank positive result was 9 in 12 patients. The number of positive
      tests after having obtained the first frank positive cardiac troponin I result
      was 10 in 12 patients. In all cases of cardiac troponin I, results were
      concordant with creatine phosphokinase-cardiac isoenzyme. In the 16 patients with
      unstable angina, only 11 patients had cardiac troponin I serum level. A total of
      21 tests were performed. In 9 patients 14 cardiac troponin I tests were < 2
      ng/ml. This was correlated with normal creatine phosphokinase-cardiac
      isoenzyme/creatine phosphokinase ratio. In 2 patients, 7 cardiac troponin I tests
      were positive. Both of them had significant increase of creatine phosphokinase
      cardiac isoenzyme/creatine phosphokinase ratio and electrocardiographic features
      of myocardial ischemia and were referred for urgent coronary angiography.
      CONCLUSION: Cardiac troponin I levels are not helpful in the initial management
      of patients with acute myocardial infarction. Thrombolytic therapy should be
      therefore instituted before the availability of cardiac troponin I results.
      However, cardiac troponin I results are concordant with creatine phosphokinase
      cardiac isoenzyme in retrospective confirmation of the diagnosis of acute
      myocardial infarction a few hours after onset. In patients with unstable angina,
      cardiac troponin I should be used mainly for risk stratification.

PMID- 12070574
TI  - Screening for congenital hypothyroidism.
AB  - OBJECTIVE: To review the screening program for congenital hypothyroidism in the
      Riyadh Al-Kharj Hospital Programme, Riyadh, Kingdom of Saudi Arabia, and to
      investigate the clinical and biochemical characteristics of affected infants.
      METHODS: The study was carried out from 1985 to 2000 in the Clinical Chemistry
      Division, Department of Pathology, Riyadh Armed Forces Hospital, Kingdom of Saudi
      Arabia. Laboratory data and case notes of infants diagnosed with congenital
      hypothyroidism were used to supply the relevant data and information. RESULTS:
      One hundred and twenty-one thousand, four hundred and four infants were screened
      over a period of nearly 15 years. The overall incidence of congenital
      hypothyroidism was 1:2759 live births with a female: male ratio of 1.8:1. The
      incidence in a rural satellite hospital was 1:1538. No seasonal variation was
      observed. Apart from jaundice, signs and symptoms of congenital hypothyroidism
      were rarely present in the neonatal period. The neonatal and maternal parameters
      of affected infants did not differ significantly from those of other infants. The
      predominant cause of congenital hypothyroidism was athyreosis (45%), followed by
      thyroid ectopia (24%) and dyshormonogenesis (17%). The mean age at the start of
      treatment of infants diagnosed in the screening program was 10.3 days.
      CONCLUSION: The screening program based on initial measurement of thyroid
      stimulating hormone in cord blood captures 97% of infants born in the Riyadh Al
      Kharj Hospital Programme. The incidence of congenital hypothyroidism was 1:2759
      live births with a female:male ratio of nearly 2:1. Congenital hypothyroidism
      infants had similar neonatal parameters as other infants. No seasonality in the
      incidence of congenital hypothyroidism was observed. In general, affected infants
      were started on thyroxine very soon after birth.

PMID- 12070575
TI  - Glycemic index of 3 varieties of dates.
AB  - OBJECTIVE: Dates are consumed worldwide and are a dietary staple for many Arabic
      people. The prevalence of type-2 diabetes mellitus is high in many developing
      communities, including many Arabic communities. The consumption of low glycemic
      index diets has been shown to have benefits for glycemic and lipid control. The
      purpose of this study was to determine and compare the glycemic indexes of 3
      varieties of commercially available dates. METHODS: The available carbohydrate
      content of the dates was determined by standard laboratory methods. Normal
      volunteer subjects were fed the commercially processed khalas, barhi, and bo
      ma'an dates. Glycemic indexes were calculated by standard methods. Results were
      calculated using means and standard deviations. Glycemic responses were compared
      by using paired t-tests. The study was performed at the Faculty of Medicine and
      Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates,
      between March 2000 and August 2001. RESULTS: The mean glycemic indexes of the
      dates were 35.5 for khalas, 49.7 for barhi and 30.5 for bo ma'an. There was a
      significant difference between the results for bo ma'an and for the other 2
      varieties. CONCLUSION: Dates can be classified as low glycemic index food items.
      There appears to be significant and unexplained differences in glycemic index
      between some date varieties. Nonetheless, the consumption of the 3 varieties of
      dates tested in this study may be of benefit in glycemic and lipid control of
      diabetic patients.

PMID- 12070576
TI  - Copper, zinc and magnesium levels in type-1 diabetes mellitus.
AB  - OBJECTIVE: Alterations in plasma concentrations of several trace elements have
      been reported to occur in type-1 diabetes mellitus. These micronutrients are
      suspected to have a role in pathogenesis and progression of the disease. METHODS:
      In a comparative analysis, the plasma concentration of copper, zinc and magnesium
      was estimated in 37 patients with type-1 diabetes mellitus and 25 healthy non
      diabetic subjects at Sher-i-Kashmir Institute of Medical Sciences, Srinagar,
      Kashmir, India. Trace elements were estimated using a GBC 902 double beam atomic
      absorption spectrophotometer. RESULTS: Mean plasma concentrations of copper and
      magnesium were comparable between diabetic patients and control subjects. Plasma
      zinc levels were significantly higher (P=0.022) in diabetic patients (17.78 0.6
      micromol/L) as compared to controls (15.80 0.75 micromol/L). Glycemic control and
      presence of microalbuminuria did not influence the plasma levels of copper, zinc
      and magnesium. CONCLUSION: Plasma zinc levels are significantly higher in type-1
      diabetes mellitus patients, while plasma copper and magnesium levels are not
      significantly altered. No effect of sex, glycemic control or presence of
      microalbuminuria could be demonstrated on plasma concentration of trace elements
      in type-1 diabetes mellitus patients.

PMID- 12070577
TI  - Conservative treatment of idiopathic detrusor instability in elderly women.
AB  - OBJECTIVE: The aim of this paper is to give an overview of the conservative
      treatment of idiopathic detrusor instability in elderly women. It describes the
      clinical and urodynamic features of the over-active bladder and the role of
      physiotherapy as well as the various physiotherapeutic techniques in the
      management of this condition. METHODS: This is a prospective, uncontrolled
      clinical trial in which 20 older women aged 55-75 years participated for 8 weeks
      duration. The study was started on April 2000 at King Fahad Hospital of the
      University, Kingdom of Saudi Arabia. Therapeutic modalities including bladder
      training, pelvic floor exercise and electrical stimulation were applied for all
      subjects. RESULTS: The first desire to void, maximum capacity, flow rate and
      voiding intervals was increased in its mean at the end of the study period
      (P<0.0001), while the means of residual volume and frequency of micturation had
      significantly decreased at the end of the study (P< 0.0001). CONCLUSION: The
      study shows that correctly taught pelvic floor exercise, combined with bladder
      training, electrical stimulation and restriction of fluids' intake are effective
      treatment modalities for the idiopathic detrusor instability in elderly women.

PMID- 12070578
TI  - A new method to aid complete lymphadenectomy in radical treatment of cancer of
      the cervix.
AB  - OBJECTIVE: A simple, new and not previously reported method to improve the
      complete ablation of the pelvic lymph nodes in the surgical treatment of cervical
      cancer is briefly reported. METHODS: Fourteen patients had been operated upon at
      Zahrawi Maternity Hospital, Damascus, Syria using radical Wertheim hysterectomy
      for surgical treatment. Five to 10 days prior to surgery, patients are given
      intramuscular iron injections that help easy visualization of the lymph nodes
      during operation. RESULTS: In all the 14 cases treated with this simple pre
      operative medication, pelvic lymph nodes were easily identified and completely
      removed. CONCLUSION: Pre-operative iron injections help in better identification
      of even the smallest pelvic lymph nodes and improve their complete removal.

PMID- 12070579
TI  - Frequency of neutrophil alloantigens by polymerase chain reaction.
AB  - OBJECTIVE: Neutrophil alloantigens are responsible for a number of immune
      clinical disorders such as neonatal alloimmune neutropenia, febrile transfusion
      reaction and transfusion related acute lung injury. Recent progress enabled
      typing of neutrophil antigens by deoxyribose nucleic acid based techniques. In
      this study we report for the first time the frequency distribution of human
      neutrophil antigen system-one in Saudis. METHODS: Blood samples were collected
      from 100 successive healthy Saudi male blood donors presenting to Regional
      Laboratory and Blood Bank, Dammam, Kingdom of Saudi Arabia in 1997. Human
      neutrophil antigen typing was carried out using polymerase chain reaction
      sequence specific primer method. RESULTS: Our results show that human neutrophil
      antigen system-one is highly polymorphic in this population and similar in its
      distribution to the Hispanic and Native Americans but different from the
      Caucasians, Indians and Africans. CONCLUSION: We found the polymerase chain
      reaction-sequence specific primer method to be a practical technique for
      neutrophil alloantigen typing. We recommend introducing this technology in
      tertiary care hospitals to allow easier diagnosis of immune neutropenias.

PMID- 12070581
TI  - Pattern of blood procurement, ordering and utilization in a University Hospital
      in Eastern Saudi Arabia.
AB  - OBJECTIVE: The main objectives of this study were to review blood procurement,
      ordering, utilization, and causes of discarding blood in a University hospital
      and provide recommendations for improvement. The study was also aimed at sheding
      light on the frequency of seropositivity for certain disease markers in blood
      donors. METHODS: This review comprised a retrospective 5-year analysis from
      January 1996 to December 2000 at King Fahad Hospital of the University, Al
      Khobar, Kingdom of Saudi Arabia. RESULTS: In this study, the most common donors
      were replacement (46%) and statutory donors (35%), while volunteer blood donors
      comprised a lower percentage (19%). There was a high crossmatch transfusion ratio
      (2.96:1) and similarly a high percentage of cancelled transfusions after
      crossmatching (66.2%). The 2 most commonly ordered blood components were packed
      red blood cells (45.7%) and random platelet concentrates (19.2%). The infective
      causes for discarding blood were: hepatitis B core antibody seropositivity
      (16.9%), hepatitis B surface antigen seropositivity (2.4%) followed by hepatitis
      C antibody seropositivity (1.5%), and rapid plasma reagin (serological test for
      syphilis) positivity (1%). The common non-infective causes of discarding blood in
      descending order or frequency were: expired unit shelf life (3.6%), positive
      donor antibody screen (0.7%), red blood cell morphological abnormalities (0.4%),
      and blood unit insufficient quantity (0.3%). Release of emergency uncrossmatched
      blood ranged at 0.6% during the study period. CONCLUSION: Performing blood bank
      internal audits and reviewing statistics are vital tools for a successful blood
      transfusion service. Implementing policies such as type and screen and the
      maximum surgical blood-ordering schedules will lead to monetary savings and more
      effective blood utilization. Drives for enhancement of volunteer blood donors are
      recommended.

PMID- 12070580
TI  - Clinical and laboratory features of congenital factor XIII deficiency.
AB  - OBJECTIVE: This is a retrospective analysis of the clinical and laboratory
      features of 17 cases of factor XIII deficiency that were followed in tertiary
      care hospitals in Riyadh, Kingdom of Saudi Arabia, over 20 years. Cases were
      referred to these hospitals from other health care centers in the country.
      METHODS: We performed a retrospective analysis of 17 cases of factor XIII
      deficiency comprising 11 males and 6 females, who were seen over a period of 20
      years (1978-1998) in Riyadh, Kingdom of Saudi Arabia. Data variables including
      age, sex, origin, clinical presentation, bleeding time, prothrombin time, partial
      thromboplastin time, factor XIII screening and assay, hemoglobin, and platelet
      count were collected and analyzed. The diagnosis of factor XIII deficiency was
      made by urea clot lysis test alone in one patient and urea clot lysis test in
      combination with factor XIII quantitative assay in 16 patients. RESULTS: Eleven
      patients were males and 6 were females. Median age at the time of diagnosis was 9
      years (3-29 years). Ten patients (59%) had a family history of excessive
      bleeding. Presenting symptoms included ecchymosis and recurrent hematomas in 12
      patients (71%), bleeding after circumcision in 6 male patients (55%), umbilical
      stump bleeding in 7 (41%), poor wound healing and keloids in 3 patients (18%),
      and intracranial bleeding in 3 patients (18%). Other manifestations included
      cephalohematoma, abortion, abruptio placenta, and intraperitoneal bleeding (one
      patient each). Laboratory evaluation revealed a normal prothrombin time, partial
      thromboplastin time, bleeding time and platelet count in all patients. Factor
      XIII screening test was positive in all 17 patients tested and assay for factors
      XIII was <0.06 U/ml in 16 patients tested. CONCLUSION: Our data confirms that
      factor XIII deficiency is a rare bleeding disorder characterized by variable
      bleeding manifestations but consistent laboratory findings. The occurrence of
      keloid in our patient group may reflect the poor quality of the clotting,
      associated with loss of tensile strength of fibrin polymers, caused by factor
      XIII deficiency and leading to abnormally large scar formation.

PMID- 12070582
TI  - Patterns of presentation of malaria in a tertiary care institute in Saudi Arabia.
AB  - OBJECTIVE: The occurrence of malaria in a non-endemic area is an exceptional
      event. Review of clinical experience at the King Faisal Specialist Hospital &
      Research Centre (a tertiary medical centre located in a non-endemic area)
      demonstrated a relatively frequent infection rate among patients. We therefore
      examined circumstances that could contribute to the high rate of occurrence
      observed. METHODS: We retrieved archived blood smears of patients diagnosed with
      malaria from the records of the Hematology Section of King Faisal Specialist
      Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia, followed by a review
      of the clinical records to extract demographic data, clinical presentations
      including history of proximate blood transfusion, and travel to, or residence in,
      areas endemic for malaria. RESULTS: There were 217 patients diagnosed with
      malaria between 1978 and 1999, (1398 to 1419 Hejira calendar) resulting in an
      average yearly frequency of 9.86 cases. Males were 2.6 times more frequently
      affected than females (p<0.001). The majority of patients were infected through
      natural means, either by residence in endemic areas (N=83) or by travel to one
      (N=90). A significant minority, 44 (20.3%), became infected through blood
      transfusion. The majority of blood transfusion-induced malaria occurred in
      patients who were immunocompromised for various reasons, mostly related to
      dysfunction of the hematopoietic system or to major surgical insult. The most
      frequently implicated organism was Plasmodium falciparum, accounting for 74.2% of
      cases, whilst Plasmodium vivax accounted for 25.4%. CONCLUSION: We demonstrate
      that patients presenting with malaria are more likely to be males who have been
      exposed during travel to endemic areas or through blood transfusion. In all
      cases, Plasmodium falciparum is the most likely organism to be implicated.

PMID- 12070583
TI  - Surgery and postoperative mebendazole in the treatment of hydatid disease.
AB  - OBJECTIVE: Surgery was virtually the only curative method for hydatid disease
      until the early 1970s when studies have shown the safety and effectiveness of
      benzomidazole compounds for the treatment of hydatid cysts. Our aim is to
      establish the outcome of chemotherapy in the postoperative period on secondary
      hydatid cyst. METHODS: Between 1987 to 1996 inclusive, all patients who were
      diagnosed with hepatic hydatid disease and who underwent surgery and received a
      post operative course of chemotherapy at Princess Basma Teaching Hospital, Irbid,
      North Jordan, were retrospectively reviewed with special referral to side effects
      of chemotherapy and recurrence rate of hydatid disease. RESULTS: There were 78
      patients (41 females, 37 males). All age groups were involved with an age range
      of 8-70 years. The main clinical presentation was upper abdominal discomfort,
      heaviness and mild pain. Ultrasonography and indirect hemagglutination test
      diagnosed more than 90% of cases. All patients were operated upon and received a
      postoperative prophylactic course of mebendazole. We reported a recurrence rate
      of less than 3%. Excessive loss of hair as a side effect to mebendazole therapy
      occurred in 2 young female patients. CONCLUSION: The postoperative prophylactic
      course of mebendazole is reliable, safe and with minor side effects and the
      recurrence rate of the disease was reduced to the lowest possible levels.

PMID- 12070584
TI  - Impaired renal function among children in Alexandria, Egypt.
AB  - OBJECTIVE: Impairment of renal function may occur as a result of a variety of
      conditions. Progression to chronic renal-disease may be prevented by early
      detection. This epidemiologic study aimed at revealing the predisposing factors
      and determinants for the development of impaired renal function among Egyptian
      children. METHODS: This is a case-control study conducted at Alexandria
      University Children's Hospital, Alexandria, Egypt. All cases below 12 years of
      age diagnosed with impaired renal function over a total duration of 6 months
      (October 1999 through to March 2000) were investigated. The primary study tool
      was a structured questionnaire, which focused on variables suspected to play a
      role in the impairment of renal function. For each patient, one control matched
      for age and sex was selected. RESULTS: Primary renal disease tends to account for
      a relatively small proportion of the etiologies of renal impairment in Egyptian
      children. Most of the cases encountered in this study suffered functional renal
      impairment secondary to severe dehydration or sepsis. Presence of congenital
      abnormalities of the gastrointestinal tract, heart or urinary tract, increased
      the possibility of suffering from impaired renal function approximately 9 times.
      Delays in seeking medical advice increased the risk substantially. CONCLUSION:
      Awareness of individuals at an increased risk, along with early diagnosis and
      adequate management of many predisposing conditions could prevent progression to
      more severe renal disease which has potentially devastating effects on every
      aspect of a childs' life.

PMID- 12070585
TI  - Articular chondrocalcinosis in Saudi Arabia.
AB  - OBJECTIVE: To investigate the prevalence of articular chondrocalcinosis in
      subjects aged 50 years and above in a radiographic survey through 14 primary care
      clinics in North Riyadh, Kingdom of Saudi Arabia. METHODS: Over a period of 7
      months extending from September 1998 to March 1999, 153 patients attending 14
      primary care clinics in North Riyadh, Kingdom of Saudi Arabia, were interviewed,
      examined and then requested to have radiographs of knees (anteroposterior and
      lateral), wrists and hands. The x-rays were read for the presence of
      chondrocalcinosis. RESULTS: One hundred and fifty three subjects over the age of
      50 years (90 males, 63 females) completed the requested x-rays. Six (3.9%) cases
      of articular chondrocalcinosis were identified in the whole age group (50-93).
      When age group above 60 are considered, the prevalence rises to 6.7%. CONCLUSION:
      We conclude that chondrocalcinosis is not rare in Kingdom of Saudi Arabia and
      increases with advancing age.

PMID- 12070586
TI  - Caries prevalence, severity and pattern in pre-school children.
AB  - OBJECTIVE: To determine the prevalence, severity and pattern of caries in
      preschool children of Al-Ahsa, Kingdom of Saudi Arabia. METHODS: Three hundred
      and twenty two randomly selected pre-school children were examined in
      kindergartens of Al-Ahsa, Kingdom of Saudi Arabia for dental caries using World
      Health Organization criteria for the diagnosis of caries. The study was completed
      in 2000. RESULTS: The mean decayed missing and filled teeth score in the 322 pre
      school children examined was 2.92 (standard deviation 3.51) with decay component
      as the major contributor in the decayed missing and filled teeth score. The
      difference between mean decayed missing and filled teeth scores was not
      significant in relation to gender, type of kindergarten (government or private)
      and area (urban or rural). The difference between mean decayed missing and filled
      teeth scores of 4-year-old and 5-year-old children was statistically significant.
      Of the 322 children examined, 202 (62.7%) were caries positive. There was no
      significant difference for caries prevalence in relation to gender, type of
      kindergarten and area. But, the difference in caries prevalence between various
      age groups was statistically significant. The mandibular first molars were the
      most carious teeth followed by mandibular 2nd molars and maxillary central
      incisors. The least affected teeth were mandibular central incisors. CONCLUSION:
      The mean decayed missing and filled teeth score and caries prevalence in the
      studied pre-school children is high as compared with children from developed
      countries. A major decay component indicates a high percentage of untreated
      caries. A high percentage of carious maxillary incisors indicate a nursing caries
      pattern.

PMID- 12070587
TI  - Use of antiplatelets and lipid lowering therapy in patients with peripheral
      vascular disease undergoing surgery [corrected].
AB  - OBJECTIVE: To investigate the use of antiplatelet and lipid lowering therapy
      among patients undergoing peripheral vascular surgery, and to compare their use
      with that reported among a similar population of patients in Canada. METHODS:
      Chart review of a cohort of 52 patients undergoing peripheral vascular surgery.
      The study was carried out at King Fahad National Guard Hospital, Kingdom of Saudi
      Arabia in May 2000. RESULTS: On discharge, less than 50% of the patients received
      any antiplatelet or antithrombotic medication. Only 13% of the patients received
      lipid-lowering therapy. Those findings parallel those of Canadian publications.
      CONCLUSION: Current literature supports the use of anti platelet and lipid
      lowering therapy among patients with peripheral vascular disease. In King Fahad
      Hopsital, National Guard, Kingdom of Saudi Arabia, the use of those beneficial
      interventions is likely sub-optimal. Factors other than randomized clinical trail
      derived evidence likely influence practice and behavior. Whether dissemination of
      evidence may change such a pattern of behavior requires further study.

PMID- 12070588
TI  - An unusual complication of sternal and clavicle osteomyelitis in a child with
      sickle cell disease.
AB  - We report an unusual child with sickle cell disease, in which osteomyelitis of
      the sternum and clavicle was diagnosed at the same time. The standard x-ray
      failed to demonstrate the lesion. Magnetic resonance imaging was very helpful in
      locating the site and degree of involvement. We recommend the use of magnetic
      resonance imaging to delineate such findings.

PMID- 12070589
TI  - Adult lead poisoning from a herbal medicine.
AB  - A 56-year-old Indian lady presented with one week history of abdominal pain,
      jaundice and chronic polyarthralgia. She had evidence of hemolytic anemia and
      hepatitis. Her blood lead level was high and a peripheral blood film showed dense
      basophilic stippling. It is believed that the lead toxicity was due to the use of
      Indian herbal medicine.

PMID- 12070590
TI  - Volvulus of the sigmoid colon in a child.
AB  - Sigmoid volvulus although a common cause of large bowel obstruction in the
      elderly, is considered rare in the pediatric age group. We report a case of
      sigmoid volvulus in a 10-year-old child with mental retardation and myopathy. The
      various predisposing factors for sigmoid volvulus in children are discussed, and
      the literature on the subject is also reviewed.

PMID- 12070591
TI  - The Middle-East connection of Wolman Disease.
AB  - The clinical, laboratory and cytological features of 2 Bahraini infants with
      Wolman's disease are described. While one of the cases showed the classical
      diagnostic features, the other case exhibited a few atypical features such as
      lack of adrenal calcification and unusual morphology of vacuolated marrow
      macrophages. Literature review shows that this disorder may not be rare in this
      region.

PMID- 12070592
TI  - Sandhoff disease (GM2 Gangliosidoses) in a premature patient with
      bronchopulmonary dysplasia.
AB  - We report a female premature infant with bronchopulmonary dysplasia and Sandhoff
      disease. The clue for diagnosis was the fundoscopy examination. We discuss this
      rare disease with unusual presentation of intrauterine growth retardation,
      premature delivery, and bronchopulmonary dysplasia.

PMID- 12070593
TI  - Hirschsprungs disease in Western Saudi Arabia.

PMID- 12070594
TI  - Necrotizing fasciitis.

PMID- 12070595
TI  - Telomere lengthening in telomerase-negative cells: the ends are coming together.
AB  - Telomeres are crucial for chromosomal stability and cell viability. Activation of
      telomerase, a specialized reverse transcriptase, is the predominant mechanism for
      maintaining telomere length and function in yeasts and human cells. Telomere
      maintenance is regarded as a key element in the immortalization of cells and
      hence in oncogenesis. Although more than 90% of all malignant tumors display
      telomerase activity, there appear to be alternatives to this mechanism.
      Alternative lengthening of telomeres (ALT) in the absence of telomerase has been
      described in various organisms and recently also in immortalized and transformed
      human cells. This article will discuss how ALT is detected and how it affects
      telomere morphology. It will review the frequency and relevance of ALT in in
      vitro immortalized cell lines, tumor-derived cell lines, and primary tumors. We
      have only begun to link mechanisms by means of which ALT may act in immortalized
      human cells to the growing knowledge about telomeres, and we can look forward to
      further fascinating insights into telomere biology. Our review will also
      emphasize recent advances in our understanding of the induction and repression of
      ALT and the demonstration of ALT in cancer cells in the light of new treatment
      strategies targeted against telomere maintenance mechanisms.

PMID- 12070596
TI  - Correlation between vascular endothelial growth factor, angiogenesis, and tumor
      associated macrophages in invasive ductal breast carcinoma.
AB  - Angiogenic and anti-angiogenic factors, secreted by tumor, inflammatory, and
      stromal cells play an important role in regulation of neovascularization. Among
      the most important of these is vascular endothelial growth factor (VEGF), a
      specific mitogen for endothelium, which increases vascular permeability and
      induces proteolytic enzymes necessary for vascular remodeling. Tumor-associated
      macrophages (TAMs) can express complex functions related to tumor biology,
      including growth, proliferative rate, stroma formation and dissolution, and
      neovascularization. The aim of this study was to define, using
      immunohistochemical analysis, the microvessel density (MVD), VEGF expression, and
      TAMs level in 97 human invasive ductal breast carcinomas not otherwise specified
      (NOS), investigate a possible relationship between them and then correlate their
      values with tumor grade, mitotic activity index (MAI), tumor size and lymph-node
      status. Statistical analysis showed a strong positive relationship between MVD
      and VEGF expression ( P<0.001). Furthermore, both MVD and VEGF expression were
      significantly correlated with tumor grade and lymph-node status, and TAMs
      infiltration with MAI. TAM level showed a significant positive connection with
      VEGF expression and MVD. These in situ observations suggest that VEGF stimulates
      angiogenesis in human invasive ductal breast carcinoma NOS and attracts
      macrophages to the tumor locus, which then may be involved in angiogenesis
      promotion. The expression of this angiogenic molecule, and MVD and TAM level, can
      provide additional prognostic significance and help in the identification of
      patients who need postoperative adjuvant therapy.

PMID- 12070597
TI  - Stromal expression of CD10 in invasive breast carcinoma: a new predictor of
      clinical outcome.
AB  - CD10 is a cell surface neutral endopeptidase that is not consistently expressed
      in the stromal cells of the normal breast. Expression of CD10 is sometimes
      observed in the stromal cells of invasive ductal carcinoma, but its clinical
      significance has never been studied. Immunohistochemical examination of CD10 was
      performed in 123 cases of breast cancer. The median follow-up period of all
      patients was 8.0 years, and univariate and multivariate analyses were performed
      to evaluate the prognostic significance of stromal CD10 expression. There was no
      staining in the stromal cells of 13 non-invasive ductal carcinomas or normal
      breast tissue. Of 110 invasive ductal carcinomas, 20 cases (18%) in which more
      than 10% of the stromal cells stained positive throughout the cancer tissue were
      judged "positive". The frequency of positive stromal staining was significantly
      higher in the cases with axillary lymph-node metastasis ( P=0.038), but there
      were no correlations between stromal CD10 expression and age, tumor size,
      histologic grade, or clinical stage. The patients whose tumors contained CD10
      positive stromal cells had a shorter metastasis-free interval ( P=0.0008).
      Univariate analysis demonstrated that patients with lymph-node metastasis also
      had a significantly shorter metastasis-free interval (metastasis vs no
      metastasis; P=0.0318). In the multivariate analysis, only CD10 remained a
      significant predictor for time to recurrence ( P=0.0059), and CD10 was the single
      significant prognostic factor for overall survival in the univariate analysis (
      P=0.0021). These results suggest that stromal expression of CD10 in breast cancer
      is an important novel prognostic factor.

PMID- 12070598
TI  - Expression of cyclo-oxygenase-2 in human tongue carcinoma and its precursor
      lesions.
AB  - The expression of Cox-2 protein was studied by immunohistochemistry in normal
      oral mucosa and in mucosa with various lesions of oral leukoplakia, including
      hyperplasia and dysplasia of squamous epithelium and frank invasive squamous
      carcinoma. A gradient of Cox-2 staining was found: the expression of Cox-2 was
      lowest in normal epithelium, somewhat increased in hyperplastic epithelium,
      further increased in dysplastic epithelium, and highest in invasive squamous cell
      carcinomas. The presence of Cox-2 in squamous cell carcinomas of the oral mucosa
      and its precursor lesions indicate that Cox-2 could participate in the
      carcinogenic process of these oral malignancies.

PMID- 12070599
TI  - Mixed mucinous-type and non-mucinous-type adenocarcinoma of the lung:
      immunohistochemical examination and K- ras gene mutation.
AB  - Mucinous-type adenocarcinoma and non-mucinous-type adenocarcinoma are known to be
      the representative histological subtypes of bronchioloalveolar carcinoma.
      Mucinous-type adenocarcinoma is also known to carry abnormalities of the K- ras
      gene at high frequency. However, the mixed subtype of the both mucinous-type and
      non-mucinous-type adenocarcinoma (mixed-type) has not been analyzed in detail,
      although its existence has been reported in a few papers. In this study we
      carried out immunohistochemical and molecular biological analyses of 15 examples
      of the mixed-type, in comparison with 11 cases of mucinous-type and 21 cases of
      non-mucinous-type adenocarcinoma. Immunohistochemically, lysozyme - one of the
      specific markers of mucinous-type adenocarcinoma - was not stained in the
      mucinous component of the mixed-type. K- ras gene mutations were detected only in
      mucinous-type (73%) and non-mucinous-type (10%) adenocarcinomas and not in either
      the mucinous or non-mucinous component of the mixed-type (0%). Therefore,
      although mixed-type adenocarcinomas consist of tumor cells showing both mucinous
      and non-mucinous morphology, the mucinous component of this type differs from
      mucinous-type adenocarcinoma in terms of immunohistochemical features and K- ras
      gene alteration.

PMID- 12070600
TI  - Numerical chromosomal aberrations in papillary renal cortical tumors:
      relationship with histopathologic features.
AB  - Previous studies have indicated that a combined trisomy of chromosomes 7 and 17
      is a constant finding in papillary renal cortical adenomas and that papillary
      renal cell carcinomas are marked by additional trisomies such as trisomy 12, 16,
      and 20. The aim of our study was to compare this cytogenetic classification of
      papillary renal cortical tumors with conventional histopathologic classification.
      We performed interphase cytogenetics with enumeration probes for chromosomes 7,
      12, 16, 17, and 20 on 41 papillary tumors found in 21 nephrectomy and 10 autopsy
      kidneys. A total of 38 tumors harbored gains of chromosomes 7 or 17, and most of
      these showed a trisomic signal distribution. The three tumors with normal copy
      numbers for chromosomes 7 and 17 were a papillary grade-2 carcinoma, a small
      adenoma (both with distinctive oxyphilic cytoplasm), and a papillary carcinoma
      with focally clear cells. Gains for chromosomes 12, 16, or 20 were found in 21
      tumors and were significantly associated with the presence of histologic criteria
      of malignancy ( P<0.0001). Histopathologic and cytogenetic features of malignancy
      were found in eight tumors smaller than 10 mm. There is a good agreement of
      cytogenetic and histopathologic criteria of malignancy in papillary renal cell
      tumors. Interphase cytogenetics might give useful additional information in cases
      of doubt or when only small biopsy specimens are available.

PMID- 12070601
TI  - Immunohistochemical and molecular analysis of p53, RB, and PTEN in malignant
      peripheral nerve sheath tumors.
AB  - The molecular basis of both sporadic and neurofibromatosis type 1 (NF1)
      associated malignant peripheral nerve sheath tumors (MPNSTs) is yet largely
      undetermined. Therefore, we analyzed a series of 12 MPNSTs - including two cases
      which arose in the setting of NF1 - for molecular alterations in the p53,
      retinoblastoma ( Rb), and PTEN tumor suppressor genes. Furthermore, the
      immunohistochemical expression of p53, RB, and PTEN protein was examined in these
      tumors. One mutation (8%), an A to T transversion leading to an amino acid
      exchange, was found in exon 5 of the p53 gene in a sporadic MPNST. In two other
      sporadic tumors (20%), loss of heterozygosity (LOH) of the p53 gene occurred.
      Nuclear overexpression of p53 protein was observed in ten tumors (83%). Loss of
      RB protein expression was seen in two MPNSTs (17%), and LOH of the Rb gene was
      detected in four tumors (44%), including the two NF1-associated MPNSTs, one of
      them showing concomitant loss of RB protein expression. No mutation in the PTEN
      gene was detected, and cytoplasmic immunoreactivity for the PTEN protein was
      maintained in eight MPNSTs (67%). We suggest that alterations in the p53 and RB
      pathway, both are essential in controlling the cell-cycle progression, are
      critical points in the tumorigenesis of sporadic and NF1-associated MPNSTs,
      whereas the PTEN gene seems to play no significant role in this process.

PMID- 12070602
TI  - Establishment and characterization of transplantable tumor line (KB) and cell
      lines (KB-P and KB-D8) from a rat thymus-derived dendritic cell sarcoma.
AB  - A transplantable tumor line (KB) was established in syngeneic rats from a
      naturally occurring sarcoma that had arisen in the thymus of a 24-month-old male
      F344 rat. Further, a cell line (KB-P) was induced from KB and a cloned cell line
      (KB-D8) was isolated from KB-P. The primary thymic tumor and KB tumors showed
      heterogeneous histological growth patterns such as sheet-like, ill-defined
      bundle, fascicular and interwoven fashions, consisting of spindle cells, oval
      cells and histiocytic large round cells. Immunohistochemically, neoplastic cells
      in KB tumors and KB-P and KB-D8 cultures reacted to vimentin and were labeled
      with antibodies of OX6 (for rat major histocompatibility complex class-II
      antigens), ED5 (for rat follicular dendritic cells; FDCs) and RED-1 (for
      interdigitating dendritic cells) in varying degrees, indicating that neoplastic
      cells exhibited the immunophenotypes of rat dendritic cells. In addition,
      neoplastic cells were immunoreactive to ED1 (for rat monocytes/macrophages) and
      ED2 (for rat tissue macrophages), and also showed positive reactions to
      histiocytic lysosomal enzymes such as acid phosphatase and non-specific esterase.
      Ultrastructurally, neoplastic cells had cell surface projections, cisterna-like
      structures and variously developed lysosomes in the cytoplasm. Based on these
      findings, the present tumor was regarded as dendritic cell-derived sarcoma
      capable of expressing macrophage-like and histiocytic nature. A reverse
      transcription polymerase chain reaction method revealed that the addition of
      lipopolysaccharide dose dependently increased the expression of mRNA of
      transforming growth factor-beta1, a proinflammatory factor, in KB-D8 cells. The
      transplantable line (KB) and cell lines (KB-P and KB-D8) may become useful tools
      for studying the histogenesis and pathobiological functions of dendritic cells.

PMID- 12070603
TI  - Leukotriene A(4)-hydrolase expression and leukotriene B(4) levels in chronic
      inflammation of bacterial origin: immunohistochemistry and reverse-phase high
      performance liquid chromatography analysis of oral mucosal epithelium.
AB  - Chronic inflammation of the oral epithelium of bacterial origin is associated
      with elevated leukotriene B(4) (LTB(4)) levels. We investigated leukotriene A(4)
      (LTA(4))-hydrolase expression and LTB(4) levels in oral epithelium in relation to
      the clinical disease manifestation and immunohistopathology and LTA(4)-hydrolase
      expression in cultured oral keratinocytes. In 11 patients, three different types
      of biopsy specimens of the oral mucosa tissues were examined. Each sample was
      divided, and one-half was analysed using immunohistochemistry with antibodies to
      LTA(4)-hydrolase, CD1a, CD3, CD19, macrophages/monocytes and granulocytes. The
      other half of the sample was homogenised and analysed using reverse-phase high
      performance liquid chromatography to determine LTB(4) levels. We found strong
      LTA(4)-hydrolase expression in basal cells of the oral epithelium from tissue
      samples that appeared clinically healthy; however, histologically a mild chronic
      inflammation was observed. In contrast, patients with symptoms of an inflammation
      of the oral mucosa showed only weak LTA(4)-hydrolase staining of the epithelial
      cell layers, but strong immunoreactivity in endothelial and invading inflammatory
      cells. LTB(4) levels were elevated in inflamed tissues compared with non-inflamed
      controls. Most significantly, there was a strong association between the
      immunohistochemical detection of the enzyme, LTB(4) levels, cellular infiltration
      and the clinical disease manifestations. In vitro experiments indicated that
      LTA(4)-hydrolase expression may be induced by bacterial contamination. This study
      suggests that LTA(4)-hydrolase expression and elevated LTB(4) levels in oral
      mucosal epithelium are integral parts of the induction and progression of chronic
      inflammatory reactions. Epithelial cells may participate in early stages of
      inflammation as a source of LTB(4).

PMID- 12070604
TI  - Ultrasonographic autopsy (echopsy): a new autopsy technique.
AB  - Autopsy has been one of the most important techniques for the development of
      modern medicine, mainly during the nineteenth century and the first half of last
      century. However, in the last few years, the number of autopsies performed in
      hospitals has dramatically decreased all over the world. This loss of interest
      can be attributed both to important advances in other diagnostic and therapeutic
      techniques and to the fear of malpractice suits. Several groups have tried to
      overcome this problem, developing different autopsy techniques, one of which is
      needle autopsy. Most authors using this technique have acknowledged that it is
      difficult to obtain material from certain organs and lesions, which makes its
      diagnostic reliability worse than that of conventional autopsy. To overcome this
      drawback, our team has recently developed a modification of needle autopsy,
      called ultrasonographic autopsy or echopsy, in which samples are obtained under
      ultrasonographic control. We report the results of the first 100 cases of echopsy
      performed in our hospital, comparing this technique with conventional autopsy
      performed on all the corpses. The concordance rate for the cause of death and the
      main pathological diagnosis between echopsy and classical autopsy was 83% in our
      series, which makes echopsy a feasible and reliable alternative to conventional
      autopsy in cases in which families refuse to give their consent for classical
      autopsy or in cases of infectious diseases.

PMID- 12070605
TI  - The significance of secondary neoplasms of the urinary and male genital tract.
AB  - Secondary neoplasms account for some 1.6-3.0% of solid malignancies encountered
      in surgical specimens from the genitourinary tract. At autopsy the proportion is
      higher, largely due to sampling bias. The peak incidence occurs around the
      seventh decade, and male and female incidences are approximately equal at all
      sites except the kidney, which shows a male preponderance owing to an excess of
      metastatic lung cancer. Adenocarcinomas are the most common histological type of
      secondary neoplasm and may be histologically and immunohistochemically
      indistinguishable from primary neoplasms arising from colonic-type epithelial
      metaplasia. Seeding of tumour along the urinary passages does not appear to be a
      significant mechanism of metastasis, and spread from one part of the
      genitourinary tract to another is uncommon. Clinical information and ancillary
      investigations are more helpful than special histological techniques in
      differential diagnosis.

PMID- 12070606
TI  - Immunohistochemical double-staining of renal allograft tissue: critical
      assessment of three different protocols.
AB  - Quantitative analyses of renal allograft tissue using immunohistochemical double
      staining could be a useful tool to extend the existing knowledge on renal
      allograft immunopathology. Due to technical reasons, this method has been only
      rarely applied in the past. The use of indirect immunohistochemistry for double
      staining bears the risk of nonspecific cross reactions between the two staining
      sequences. To date, various procedures have been refined to avoid such cross
      reactions. Here we assessed the validity of three different protocols for
      indirect immunohistochemical double-staining on frozen sections of renal
      transplant biopsies ( n=12). Both colocalized antigens and antigens with a non
      overlapping distribution were stained according to each of the three protocols.
      Differentiation between the two staining sequences was achieved by employing
      different colored substrates of alkaline phosphatase (protocol 1), different
      enzymes (peroxidase and alkaline phosphatase) together with the use of 3,3'
      diaminobenzidine-tetrahydrochloride substrate in the first staining sequence
      (protocol 2), or primary antibodies from different species (protocol 3).
      Sensitivity and specificity of each protocol were determined by quantitative
      comparison with control single-stainings of adjacent sections. Sensitivity of the
      first staining sequence was about 100% with each of the three protocols
      investigated. In the second staining sequence, sensitivities of protocols 1 (50%)
      and 2 (54-66%) were much lower than of protocol 3 (100%). Specificity of the
      second staining sequence was only 44% with protocol 1 compared with 98% with
      protocol 2 and 100% with protocol 3. In conclusion, protocols 1 and 2 are not
      recommended for quantitative double-staining analyses. In contrast, protocol 3
      provided maximum sensitivity and specificity, even for antigens that are
      colocalized on the same cell type. Thus, the use of primary antibodies from
      different species is by far the most reliable technique for quantitative double
      staining analyses in renal allograft tissue.

PMID- 12070607
TI  - Gastric-type adenocarcinoma of the duodenal second portion histogenetically
      associated with hyperplasia and gastric-foveolar metaplasia of Brunner's glands.
AB  - We report a case of a pedunculated polyp with a focus of gastric-type
      adenocarcinoma arising in the opposite side of the papilla Vater of the duodenal
      second portion. The carcinoma was surrounded by lobules of hyperplastic Brunner's
      glands. Immunohistochemically the carcinoma tissue showed both gastric foveolar
      type mucin ( MUC5AC) and pyloric/Brunner's gland-type mucin ( MUC6), in which
      proliferating cells positive for MIB-1 (Ki-67) were scattered diffusely. Most of
      the hyperplastic Brunner's glands were positive for MUC6, while cells toward the
      lumen in the superficial layer were positive for MUC5AC and MIB-1. This
      directional pattern of differentiation of Brunner's glands has recently been
      demonstrated by our group in the histogenetic course of gastric metaplasia
      originating directly from Brunner's glands. Therefore the present carcinoma is
      thought to have developed under induction of gastric-foveolar differentiation in
      a manner very similar to that of gastric metaplasia in hyperplastic Brunner's
      glands.

PMID- 12070608
TI  - Follicular dendritic cell sarcoma of the omentum.

PMID- 12070611
TI  - Differential expression of two MyoD genes in fast and slow muscles of gilthead
      seabream ( Sparus aurata).
AB  - Members of the myogenic regulatory gene family, including MyoD, Myf5, Myogenin
      and MRF4, are specifically expressed in myoblast and skeletal muscle cells and
      play important roles in regulating skeletal muscle development and growth. They
      are capable of converting a variety of non-muscle cells into myoblasts and
      myotubes. To better understand their roles in the development of fish muscles, we
      have isolated the MyoD genomic genes from gilthead seabream (Sparus aurata),
      analyzed the genomic structures, patterns of expression and the regulation of
      muscle-specific expression. We have demonstrated that seabream contain two
      distinct non-allelic MyoDgenes, MyoD1 and MyoD2. Sequence analysis revealed that
      these two MyoD genes shared a similar gene structure. Expression studies
      demonstrated that they exhibited overlapping but distinct patterns of expression
      in seabream embryos and adult slow and fast muscles. MyoD1 was expressed in
      adaxial cells that give rise to slow muscles, and lateral somitic cells that give
      rise to fast muscles. Similarly, MyoD2 was initially expressed in both slow and
      fast muscle precursors. However, MyoD2 expression gradually disappeared in the
      adaxial cells of 10- to 15-somite-stage embryos, whereas its expression in fast
      muscle precursor cells was maintained. In adult skeletal muscles, MyoD1 was
      expressed in both slow and fast muscles, whereas MyoD2 was specifically expressed
      in fast muscles. Treating seabream embryos with forskolin, a protein kinase A
      activator, inhibited MyoD1 expression in adaxial cells, while expression in fast
      muscle precursors was not affected. Promoter analysis demonstrated that both
      MyoD1 and MyoD2 promoters could drive green fluorescence protein expression in
      muscle cells of zebrafish embryos. Together, these data suggest that the two non
      allelic MyoD genes are functional in seabream and their expression is regulated
      differently in fast and slow muscles. Hedgehog signaling is required for
      induction of MyoDexpression in adaxial cells.

PMID- 12070612
TI  - The genetic control of arista lateral morphogenesis in Drosophila.
AB  - The sensory bristles and epidermal hairs of Drosophila have proven to be valuable
      model cell types for studying the role of the cytoskeleton in cellular
      morphogenesis. We have recently begun to use the arista laterals as a third model
      cell type. The laterals display a combination of bristle and hair characteristics
      and provide a system where we can compare the relative importance of specific
      genes and subcellular structures for the morphogenesis of different polarized
      cellular extensions. We have characterized the lateral phenotype of a collection
      of mutations selected because of their phenotypes in hairs and bristles. In many
      but not all ways the lateral phenotypes are similar to the hair and bristle
      phenotypes. We provide compelling genetic evidence for the importance of the
      actin cytoskeleton in lateral elongation, shaping and integrity. Our observations
      provide evidence that defects in actin bundling can destabilize laterals so that
      they split during growth. Temperature shift experiments suggest that a defect in
      lateral initiation can lead to subsequent splitting. These observations provide a
      link between multiple hair and lateral cells forming by both multiple initiation
      events and by the splitting of individual cellular extensions. We also found that
      mutations that lead to lateral splitting typically alter the stereotypic
      arrangement of actin filament bundles and microtubules in laterals.

PMID- 12070613
TI  - Drosophila Yurt is a new protein-4.1-like protein required for epithelial
      morphogenesis.
AB  - Proteins of the 4.1 family play a key role in the integrity of the cytoskeleton
      and in epithelial tissue movement, as shown by the disruption of the actin
      cytoskeleton in human erythrocytes caused by genetic loss of protein 4.1, and the
      failure of epithelial tissue migration during Drosophila embryogenesis caused by
      genetic loss of the 4.1 homolog Coracle. Here we report the genetic
      characterization of Yurt, a novel protein 4.1 family member in Drosophila that is
      associated with the plasma membrane of epithelial cells. Homozygous loss-of
      function mutations in the yurt gene cause failure of germ-band retraction, dorsal
      closure, and head involution, associated with degeneration of the amnioserosa and
      followed by embryonic lethality. A mammalian homolog of Yurt is up-regulated in
      metastatic melanoma cells. These novel cytoskeletal proteins appear to play
      important roles in epithelial cell movements and in the morphogenetic tissue
      changes that depend on them.

PMID- 12070615
TI  - cDNA cloning and distribution of XEXT1, the Xenopus homologue of EXT1.
AB  - Hereditary Multiple Exostosis (EXT) is an autosomal dominant disorder. Here, we
      have isolated XEXT1, a Xenopus homologue of EXT1, as an ovary-enriched cDNA
      clone. The 2,598-bp XEXT1 cDNA had a single open reading frame encoding 735 amino
      acids. Quantitative RT-PCR analysis showed that transcripts of XEXT1 were present
      maternally and consumed prior to gastrulation. Zygotic expression of XEXT1 was
      not detected during late embryogenesis. In adult organs, XEXT1 was expressed
      intensely in bone and lung. Whole-mount in situ hybridization showed that
      maternally transcribed XEXT1 mRNAs were stored in the animal hemisphere, and were
      localized in the center of the cell during cleavage stages.

PMID- 12070614
TI  - Oocyte and embryonic cytoskeletal defects caused by mutations in the Drosophila
      swallow gene.
AB  - The maternal effect gene swallow ( swa) of Drosophila is required for bicoid and
      htsN4 mRNA localization during oogenesis. Swallow is also required for
      additional, poorly understood, functions in early embryogenesis. We have examined
      the cytoskeleton in swa mutant oocytes and embryos by immunocytochemistry and
      confocal microscopy. Mid- and late-stage swaoocytes have defective cytoplasmic
      actin networks. Stage-10 oocytes have solid actin clumps and hollow actin spheres
      in the subcortical layer, and late-stage oocytes have uniformly distributed
      hollow actin spheres in the subcortical layer and in deeper cytoplasm. Swa
      preblastoderm embryos have uneven and irregularly distributed actin at the
      cortex, and defective subcortical actin networks that contain hollow and solid
      spheres. In swa syncytial blastoderm embryos, the abnormal actin cytoskeleton is
      associated with defects in nuclear distribution, migration and cleavage. Actin
      cytoskeletal defects correlate with spindle defects, suggesting that the abnormal
      organization of the actin cytoskeleton allows interaction of mitotic spindles,
      which induces defective nuclear divisions and loss of nuclei from the surface of
      the embryo.

PMID- 12070616
TI  - kuzbanian is required cell autonomously during Notch signalling in the Drosophila
      wing.
AB  - The kuzbanian gene encodes a metalloprotease of the ADAM family that is involved
      in Notch signalling. However, its precise role is a matter of controversy. While
      original reports concluded that kuz is required on the receiving side of the
      Notch signalling pathway, a more recent report suggests that Kuz is required on
      the signal-emitting side for the generation of an active secreted form of the
      ligand Delta. In this scenario, kuz should act cell non-autonomously. A third
      possibility is that Kuz is required on the signal-emitting as well as the
      receiving side. Here I present the clonal analysis of kuz in Drosophila wing. The
      results show that Kuz acts on the receiving side of the pathway and is not
      required for Delta signalling. This further confirms the hypothesis that Kuz is
      required for the release of the intracellular domain of Notch that transduces the
      signal to the nucleus. The presented results complement recent data that indicate
      that Kuz can perform the S2 proteolytic cleavage of the Notch receptor that is
      required for its activation.

PMID- 12070617
TI  - Heart rate is lower during ergometer rowing than during treadmill running.
AB  - This study evaluated whether the heart rate (HR) response to exercise depends on
      body position and on the active muscle mass. The HR response to ergometer rowing
      (sitting and using both arms and legs) was compared to treadmill running (upright
      exercise involving mainly the legs) using a progressive exercise intensity
      protocol in 55 healthy men [mean (SD) height 176 (5) cm, body mass 71 (6) kg, age
      21 (3) years]. During rowing HR was lower than during running at a blood lactate
      concentration of 2 mmol.l(-1) [145 (13) compared to 150 (11) beat.min(-1),
      P<0.05], 4 mmol.l(-1) [170 (10) compared to 177 (13) beat.min(-1), P<0.05], and 6
      mmol.l(-1) [182 (10) compared to 188 (10) beat.min(-1), P<0.05]. Also during
      maximal intensity rowing, HR was lower than during maximal intensity running [194
      (9) compared to 198 (11) beat.min(-1), P<0.05]. These results were accompanied by
      a higher maximal oxygen uptake during rowing than during running [rowing compared
      to running, 4.50 (0.5) and 4.35 (0.4) l.min(-1), respectively, P<0.01]. Thus, the
      oxygen pulse, as an index of the stroke volume of the heart, was higher during
      rowing than during running at any given intensity. The results suggest that
      compared to running, the seated position and/or the involvement of more muscles
      during rowing facilitate venous return and elicit a smaller HR response for the
      same relative exercise intensity.

PMID- 12070618
TI  - Hyperbaric oxygenation mitigates focal cerebral injury and reduces striatal
      dopamine release in a rat model of transient middle cerebral artery occlusion.
AB  - The usefulness of the administration of hyperbaric oxygen (HBO) in the treatment
      of acute focal cerebral ischemia remains debatable. A significant association
      exists between focal cerebral injury and an excessive release of extracellular
      dopamine (DA). In vivo microdialysis was used in the present study to examine the
      effect of HBO on DA release in the striatum during ischemia and reperfusion in
      rats. The histological changes occurring were also evaluated. Focal cerebral
      ischemia was induced by occlusion of the middle cerebral artery (MCA) using a
      surgically placed intraluminal filament. Control rats (n=8) were subjected to 1 h
      of ischemia, whilst the study rats (n=8) were in addition treated with HBO (2.8
      atmospheres of absolute pressure 100% O(2)) during ischemia. Both groups were
      returned to breathing room air at normal pressure during reperfusion.
      Microdialysis samples were continuously collected at 15 min intervals at 2
      microl.min(-1). The [mean (SE)] increase in release of striatal DA attained
      significance after 30 min of occlusion of MCA [170 (24)%], and continued to
      increase [268 (26)% at 45 min] reaching a peak level at 60 min [672 (59)%] before
      returning to the baseline level during the late reperfusion phase. There was no
      significant change in the level of DA in HBO treated rats during the period of
      ischemia. A significant reduction in edema and neuronal shrinkage were observed
      by histological examination in HBO treated rats when compared to the control
      rats. The results showed that HBO, when administered during ischemia, offered
      significant neuroprotection in our experimental model of transient focal cerebral
      ischemia in the rat. The mechanism seems to imply, at least in part, a reduced
      level of DA.

PMID- 12070619
TI  - Leptin reduction after endurance races differing in duration and energy
      expenditure.
AB  - Serum leptin concentrations are reduced in the presence of a negative energy
      balance. It has been demonstrated, however, that strenuous and prolonged
      exercise, which induces a marked negative energy balance, is not always followed
      by a reduction in serum leptin levels. We therefore analysed serum leptin
      concentrations before and after three endurance races, which differed in duration
      and energy expenditure (EE), with the aim of clarifying the relationship between
      the level of EE and the reduction in leptin levels. Forty-five males participated
      in one of three competitive endurance races, a half-marathon run [21.097 km,
      estimated EE 1,400 kcal (5,852 kJ)], a ski-alpinism race [about 45 km, estimated
      EE 5,000 kcal (20,900 kJ)], and an ultramarathon race [100 km, estimated EE 7,000
      kcal (29,269 kJ)]. Blood samples for analysis of serum leptin, and plasma free
      fatty acids (FFA) were collected before and after the races. Pre-race leptin
      values were significantly correlated with both body mass index and body fat mass
      ( r=0.672 and r=0.699, respectively; P<0.0001). After exercise, serum leptin
      levels decreased significantly in the ultramarathon [from 4.15 (0.63) microg/l to
      1.01 (0.15) microg/l; P<0.001] and in the ski-alpinism race [from 1.10 (0.28)
      microg/l to 0.62 (0.15) microg/l; P<0.01], but not in the half-marathon [from
      1.38 (0.40) microg/l to 1.20 (0.36) microg/l]. Plasma FFA were found to have
      significantly increased in all three of the races, showing a negative correlation
      with the percent reduction in leptin ( r=0.369, P<0.02). Our data indicate that
      only a prolonged endurance exercise involving a high EE can induce a marked
      reduction in circulating serum leptin levels.

PMID- 12070620
TI  - Effects of equivolume isometric training programs comprising medium or high
      resistance on muscle size and strength.
AB  - Isometric unilateral elbow extension training was conducted for 10 weeks (3 times
      per week) on 12 young adult men to investigate the effects of equivolume exercise
      programs with different combinations of intensity and duration on the
      morphological and functional aspects of the triceps brachii muscle. One group of
      6 subjects trained by developing maximal voluntary contraction (MVC) for 6 s per
      set with 12 sets per session (100%G), while the other group of 6 subjects trained
      at 60% of MVC for 30 s per set with 4 sets per session (60%G). Training
      significantly increased the muscle volume ( V(m)), fascicle pennation angle of
      the triceps brachii, and torque output during concentric and eccentric elbow
      extensions at three constant velocities of 0.52, 1.57, and 3.14 rad.s(-1) as well
      as under the training condition, with no significant differences in the relative
      gains between the two programs. However, 100%G showed significantly greater V(m)
      than 60%G after training, when V(m) before training was normalized. Thus, only
      60%G significantly increased the ratio of torque to V(m) developed in the
      eccentric actions at the three velocities and concentric action at 1.57 rad.s(
      1). The present results indicate that isometric training programs of medium
      resistance/long duration and high resistance/short duration produce different
      effects on V(m) and dynamic strength relative to V(m), even if the training
      volume is equalized between the two protocols.

PMID- 12070621
TI  - Effect of support stimulation on unloaded soleus in rat.
AB  - We studied the efficacy of plantar support in the prevention of atrophy in a
      disused soleus muscle during hindlimb suspension (HS). The 14-day investigation
      involved three groups of hindlimb-suspended male Wistar rats and a group of
      control rats (C). In all HS groups, the left hindlimbs (L) of the animals were
      left free. As for the right hindlimbs (R), they were either provided support by
      an adjustable platform (Sup), or immobilized at the ankle joint in a neutral
      position (Im), or both supported by the platform and immobilized (Sup+Im). Mass,
      cross-sectional area (CSA) and slow twitch (ST) fiber percentage (ST%) in the R
      soleus muscle were similar in the Sup and control groups. In the Sup+Im group,
      these parameters were significantly lower than in the Sup R and C groups.
      However, the CSA of ST fibers in the Sup+Im R soleus was significantly higher
      than in those hindlimbs that were left hanging free. Succinate dehydrogenase
      activity in ST fibers, and alpha-glycerophosphate dehydrogenase activity in fast
      twitch fibers had decreased in the Sup R as compared with the controls. The
      maximal rate of ADP-stimulated mitochondrial respiration was increased in the
      free-hanging Sup L hindlimb in comparison with the control. In conclusion, during
      HS: (1) hindlimb support prevents slow-to-fast fiber transformation and losses in
      muscle mass and fiber CSA, but brings about a decrease in metabolic enzyme
      activity, and (2) hindlimb plantar support attenuates but does not fully prevent
      ST fiber atrophy in the immobilized soleus.

PMID- 12070622
TI  - Can increased intra-abdominal pressure in humans be decoupled from trunk muscle
      co-contraction during steady state isometric exertions?
AB  - The purpose of the present study was to investigate whether increased intra
      abdominal pressure (IAP) can be achieved without elevating the overall trunk
      muscle co-contraction that causes increased spine compression force. Ten subjects
      performed isometric trunk flexion, extension, and lateral bending exertions while
      generating 0%, 40% and 80% of their maximal IAP or while co-contracting trunk
      muscles without consciously raising IAP. An additional three subjects performed a
      variety of ramp IAP, co-contraction and isometric exertion tasks while holding
      their breaths and while exhaling. An 18 degree-of-freedom, electromyogram (EMG)
      assisted biomechanical model was used to quantify trunk muscle co-contraction
      with calculations of spine compression force and stability. Spine stability and
      compression force increased proportionally with increased IAP regardless of
      whether the subjects intentionally generated IAP or consciously avoided it. This
      increase was accomplished with significantly greater co-contraction of 12 major
      trunk muscles. The EMG activation of all muscles was highly correlated with IAP
      and intra-thoracic pressure (ITP) ( r from 0.59 to 0.95). Activity of the
      thoracic erector spinae correlated the best with ITP ( r=0.81), which in turn was
      correlated with IAP ( r=0.91). It was not possible to co-contract trunk muscles
      without generating IAP and ITP, or conversely to generate IAP without trunk
      muscle co-contraction and increased ITP.

PMID- 12070623
TI  - Effect of exercise on blood pressure in rats with chronic NOS inhibition.
AB  - Regular training lowers blood pressure in hypertensive humans and other animals.
      We investigated the response to 4 weeks of treadmill exercise training in
      hypertensive male Wistar rats receiving the nitric oxide synthase inhibitor
      N(omega)-nitro- L-arginine methyl ester ( L-NAME). The rats were on either a
      short- (4 weeks) or long-term (10 weeks) L-NAME treatment protocol and were
      subjected to running exercise that started concomitantly in the short-term group
      and in the 6th week in the long-term group. Four weeks of exercise training
      induced a fall in mean arterial pressure in both the short- [mean (SEM) 137.6
      (4.0) mmHg] and long-term hypertensive groups [161.4 (2.3) mmHg] compared to
      their sedentary hypertensive controls [160.4 (3.3) mmHg and 176.8 (8.9) mmHg,
      respectively]. Exercise also increased muscle nitric oxide synthase activity in
      both of the trained hypertensive groups. Muscle nitrite levels were higher in the
      exercising short-term hypertensive group compared to both the sedentary control
      and the sedentary hypertensive groups, and were not different between the
      sedentary and exercising long-term hypertensive groups. Increased wall thickness
      of the aortic and mesenteric vessels was observed in the hypertensive groups, but
      was prevented in the exercising long-term hypertensive group. In rat, exercise
      reduces the elevated blood pressure in L-NAME-induced hypertension via increasing
      nitric oxide synthase activity. Changes in vessel structure with exercise
      training may also be involved in the blood-pressure-lowering effects.

PMID- 12070624
TI  - Effects of sprint exercise on oxidative stress in skeletal muscle and liver.
AB  - Although numerous studies have tested the effects of continuous exercise regimens
      on antioxidant defences, information on the effect of sprint exercise on the
      antioxidant defence system and lipid peroxidation levels of tissues is scant. The
      present study was designed to determine the effects of sprint exercise on the
      lipid peroxidation and antioxidant enzyme system in liver and skeletal muscle
      during the post-exercise recovery period in untrained mice. Mice performed 15
      bouts of exercise, each comprising running on a treadmill for 30 s at 35 m.min(
      1) and a 5 degrees slope, with a 10-s rest interval between bouts. They were then
      killed by cervical dislocation either immediately (0 h), 0.5 h, 3 h or 24 h after
      completion of the exercise. Their gastrocnemius muscle and liver tissues were
      quickly removed. It was found that blood lactate levels increased immediately
      after the exercise, but had returned to control levels by 0.5 h post-exercise.
      This exercise regimen had no effect on the activity of superoxide dismutase and
      glutathione peroxidase in these tissues. Levels of muscle thiobarbituric acid
      reactive substances (TBARS) had increased at 0.5 and 3 h post-exercise, and then
      returned to control levels by 24 h post-exercise. In conclusion, acute sprint
      exercise in mice resulted in an increase in TBARS levels in skeletal muscle; no
      change was observed in the liver. Antioxidant enzyme activities remained
      unaffected by acute sprint exercise in these tissues.

PMID- 12070625
TI  - Exercise-induced oxyhaemoglobin desaturation, ventilatory limitation and lung
      diffusing capacity in women during and after exercise.
AB  - Arterial haemoglobin saturation during exercise in healthy young women [eight
      subjects mean (SEM) age 20.8 (1.8) years] was measured to confirm the theory that
      young women experience exercise-induced arterial hypoxaemia (EIAH) at a lower
      relative percentage of maximal oxygen uptake (VO(2max)) than has been documented
      in their male counterparts. To determine if flow limitation [the percentage of
      the tidal volume ( V(T)) that met or exceeded the boundary established by
      multiple maximal expiratory manoeuvres] and/or post-exercise lung diffusing
      capacity are linked to EIAH in women, and to investigate the influence of
      exercise intensity and duration on post-exercise carbon monoxide lung diffusing
      capacity ( D(L, CO)), these parameters were measured during and after three
      exercise tests (incremental test until exhaustion, 5 km run and 5 km run with
      sprint). All subjects experienced physiologically significant EIAH (a fall of
      more than 3% in oxygen saturation of arterial blood from levels at rest) and
      seven subjects experienced flow limitation during the VO(2max) protocol [mean
      (SD) 12.2 (8.8)% of V(T)]. Even though there was no significant relationship
      between aerobic capacity and the degree of flow limitation ( r=0.33, P>0.05), the
      flow limitation was related to absolute ventilation in the subjects studied (
      r=0.82, P<0.05). There was no significant relationship between decrements in post
      exercise D(L, CO) and EIAH ( r=0.05, P>0.05), however there was a strong
      correlation between the extent of flow limitation (% of V(T)) and EIAH ( r=0.71).
      Significant decreases in D(L, CO) lasted for up to 16 h after each of the
      exercise tests ( P<0.05) and lasted for a further 8 h after the maximal test (
      P<0.05). Exercise intensity was the main contributing factor to the observed
      decreases in post-exercise D(L, CO) with the percentage of VO(2max) attained
      during the various tests being significantly related to the fall in D(L, CO) for
      1, 2, 3, 16 and 24 h after exercise ( P<0.05). As the appearance of flow
      limitation closely coincided with the appearance of EIAH, the results from the
      present study suggest that flow limitation is a contributing factor to EIAH in
      women although the exact mechanism remains unclear.

PMID- 12070626
TI  - Effect of moderate exercise on salivary immunoglobulin A and infection risk in
      humans.
AB  - The incidence of upper respiratory tract infections (URTI) and salivary
      immunoglobulin A concentrations [IgA(s)] of nine individuals were examined during
      12 weeks of moderate exercise training, and compared to ten sedentary controls.
      Changes in maximal oxygen uptake were assessed at initial, mid-point and final
      evaluations (T1-3), while changes in [IgA(s)] and salivary immunoglobulin
      concentration-salivary albumin concentration ratio ([IgA(s)]:[Alb(s)]) were
      monitored at T1 and T3. During the 12 week period, symptoms of URTI were self
      recorded daily. During the period of training the level of fitness significantly
      increased ( P<0.05) in the exercise group. The number of days recording symptoms
      of influenza, but not of cold, and total light URTI symptoms was significantly
      reduced in the exercise group during the last weeks of training. A significant
      increase in [IgA(s)] and in [IgA(s)]:[Alb(s)] was found in the exercise group
      after training. Both [IgA(s)] and [IgA(s)]:[Alb(s)] were significantly related to
      the number of days showing symptoms of influenza ( P<0.01) and the total number
      of days of sickness ( P<0.05). These data provide quantitative support for the
      belief that regular, moderate exercise results in an increased [IgA(s)] at rest
      and [IgA(s)]:[Alb(s)], which may contribute to a decreased risk of infection.

PMID- 12070627
TI  - Reproducibility of the blood lactate threshold, 4 mmol.l(-1) marker, heart rate
      and ratings of perceived exertion during incremental treadmill exercise in
      humans.
AB  - The aim of this study was to investigate the reproducibility of blood lactate
      measurements, heart rate (HR) and ratings of perceived exertion (RPE) during
      treadmill exercise at speeds corresponding to the lactate threshold ( v(Th,la)-)
      and a fixed blood lactate concentration of 4 mmol.l(-1)( v(la)-(,4)). Possible
      differences in reproducibility related to fitness levels were also investigated.
      A group of 20 men [mean (SD)] [age 20.5 (1.4) years] and 16 women [age 21.2 (0.9)
      years] took part in the study. The subjects performed two identical incremental
      exercise tests consisting of at least six 4 min stages. Blood lactate
      concentrations, HR and RPE were recorded at the end of each stage. Limits of
      agreement (LoA), correlation coefficients and 95% confidence intervals for the
      mean difference between tests were employed to investigate the level of agreement
      and reproducibility of blood lactate concentration, HR and RPE. For the group as
      a whole, the sample correlation coefficient for speed at v(Th,la)- was r=0.88,
      and was r=0.92 for the speed at v(la)-(,4). At v(Th,la) -, the correlation
      coefficients for the moderately fit and unfit were r=0.94 and r=0.36,
      respectively, and at v(la)-(,4) r=0.93 and r=0.68, respectively. The LoA for the
      moderately fit group indicated that a change of 1.62 km.h(-1) in v(Th,la)- would
      be necessary to be considered a change in training status. For HR and RPE,
      relationships between the tests were generally poor. The LoA suggested that
      changes in scores must be unacceptably large. These findings cast doubt on the
      sensitivity of testing for change of blood lactate concentration, HR and RPE in
      this population.

PMID- 12070628
TI  - Intra-abdominal pressure increases during exhausting back extension in humans.
AB  - The aim of this study was to investigate in humans the effect of maintained
      spinal load on the intra-abdominal pressure (IAP), low back kinematics and trunk
      muscle activity. This study consisted of two endurance tests for the low back
      muscles performed 3 weeks apart. Nine healthy subjects participated in the study.
      In the first test (upright-test), the subject had to pull with the back muscles
      at a constant force in an upright position, and in the second test (incline
      test), the subject had to resist a constant forward pulling force while standing
      with a 45 degrees inclination of the back in relation to vertical. The IAP, rate
      of perceived exertion and electromyogram (EMG) from the erector spinae,
      iliocostalis lumborum, rectus abdominus and the external and internal oblique
      muscles were measured using surface electrodes. There was no significant
      difference in endurance time between the two tests. Both tests showed a
      significant increase in EMG amplitude with time for all muscles except the
      erector spinae muscle. A decrease in the median frequency for the erector spinae
      muscle was found indicating fatigue, and since no increase in EMG amplitude was
      found a decrease in force output from the muscle must be assumed. The IAP
      increased significantly during both tests. There was a considerable variation
      between the subjects in the size of this development, but the pattern was the
      same for all subjects. In conclusion it was found that trunk extension until
      exhaustion initiates an increase in the activity of the abdominal muscles and an
      increase in the IAP as the low back muscles become fatigued.

PMID- 12070629
TI  - Autonomic control of the cardiovascular system during sleep in normal subjects.
AB  - The autonomic control of heart rate and blood pressure during sleep is
      controversial: although it has been reported that vagal activity is more often
      lower in rapid eye movement sleep (REM) than in other stages of sleep (non-REM,
      NREM), the opposite has also been described. Initially, it was reported that
      baroreflex sensitivity (BRS) increases during sleep (REM and NREM), but in later
      studies, this was only partially confirmed. We therefore studied autonomic
      control of the cardiovascular (CV) system during sleep in 12 normal adults. The
      spectral components of the heart rate R-R interval, blood pressure (BP), and BRS
      were computed at low (LF) and actual breathing frequency (high frequency, HF).
      Analysis of sleep stage and a cycle-by-cycle stage II analysis were performed. CV
      variability is affected largely by sleep-stage and sleep-cycle organisation: NREM
      and the last cycle exhibit the greatest vagal activity and the lowest sympathetic
      activity. BRS estimation for both the LF and HF bands confirmed previous results
      obtained by pharmacological and spontaneous slope methods: BRS is greater during
      sleep than during nocturnal wake periods, and further increased in REM. BRS is
      frequency dependent: in NREM, the higher value of HF BRS compared to LF BRS
      favours the HF control of BP variability, whereas higher BRS HF and LF components
      contribute to the strongest control in REM. BRS variability exhibits no
      significant pattern during the night. Our results suggest that both sleep-cycle
      organisation and BRS estimation in the LF and HF bands should be considered in
      sleep studies of autonomic CV control.

PMID- 12070630
TI  - Changes in skeletal muscle myosin heavy chain isoform content during congestive
      heart failure.
AB  - Recent investigations have suggested that changes in contractile protein
      expression contribute to reductions in skeletal muscle function during congestive
      heart failure (CHF). Myosin heavy chain (MHC), a major contractile protein, has
      been shown to undergo alterations in protein isoform expression during CHF. The
      purpose of this investigation was twofold: (1) to determine whether muscles of
      the same functional group undergo similar changes in MHC expression, and (2)
      determine whether the magnitude of alterations in MHC is related to the severity
      of CHF. Using the rat coronary ligation model, mild and severe forms of CHF were
      produced and muscles of the plantar flexor group were analyzed. Whole-muscle MHC
      isoform proportions were not altered in the soleus and white gastrocnemius
      muscle, however significant increases in the percentage of fast MHC isoforms (7
      9% increases in MHC IIx and IIb expression) were found in the red gastrocnemius
      muscle. In addition, there were significant proportional increases (8%) in MHC
      type IIb at the expense of MHC type IIx in the plantaris muscle. Many of the
      changes in the proportions of MHC isoforms were significantly correlated with
      indices of CHF severity. This indicates that changes in skeletal muscle MHC
      isoform expression are related to the severity of CHF and suggests that some
      peripheral skeletal muscles are more susceptible to shifts in MHC expression due
      to CHF. These changes in MHC isoform expression may contribute to alterations in
      the physiological performance of skeletal muscle and exercise capacity during
      CHF.

PMID- 12070631
TI  - Enhanced chemosensitivity after intermittent hypoxic exposure does not affect
      exercise ventilation at sea level.
AB  - The purpose of the present study was to test the hypothesis that the ventilatory
      response to exercise at sea level may increase after intermittent hypoxic
      exposure for 1 week, accompanied by an increase in hypoxic or hypercapnic
      ventilatory chemosensitivity. One group of eight subjects (hypoxic group) were
      decompressed in a chamber to 432 torr (where 1 torr=1.0 mmHg, simulating an
      altitude of 4,500 m) over a period of 30 min and maintained at that pressure for
      1 h daily for 7 days. Oxygen uptake and pulmonary ventilation (V(E)) were
      determined at 40%, 70%, and 100% of maximal oxygen uptake at sea level before
      (Pre) and after (Post) 1 week of daily exposures to hypoxia. The hypoxic
      ventilatory response (HVR) was determined using the isocapnic progressive hypoxic
      method as an index of ventilatory chemosensitivity to hypoxia, and the
      hypercapnic ventilatory response (HCVRSB) was measured by means of the single
      breath carbon dioxide method as an index of peripheral ventilatory
      chemosensitivity to hypercapnia. The same parameters were measured in another
      group of six subjects (control group). In the hypoxic group, resting HVR
      increased significantly ( P<0.05) after intermittent hypoxia and HCVRSB increased
      at Post, but the change was not statistically significant ( P=0.07). In contrast,
      no changes in HVR and HCVRSB were found in the control group. There were no
      changes in either V(E) or the ventilatory equivalent for oxygen during maximal
      and submaximal exercise at sea level throughout the experimental period in either
      group. These results suggest that the changes in resting hypoxic and peripheral
      hypercapnic chemosensitivities following short-term intermittent hypoxia have
      little effect on exercise ventilation at sea level.

PMID- 12070632
TI  - Critical review of the epidemiological literature on the potential cardiovascular
      effects of occupational carbon disulfide exposure.
AB  - OBJECTIVES: Occupational carbon disulfide (CS(2)) exposure has been associated
      with a variety of health effects since its introduction in the mid-19th century.
      Much of the epidemiological interest, especially since the 1960s, has focused on
      associations with cardiac effects. However, considerable differences in study
      approach, disease outcome, CS(2) exposure level, and control of confounding
      factors have produced mixed results and conclusions. This critical review
      presents a synthesis of the most relevant and best quality studies to better
      understand these associations. METHODS: Using specific criteria to assess
      methodological and scientific quality, we identified 37 studies with the
      potential to inform on at least one of the following questions: (1) Has a
      relationship between CS(2) exposure and coronary heart disease (CHD) mortality
      been reasonably demonstrated? If so, at what apparent exposure levels has it been
      observed? (2) Among studies of workers routinely exposed to CS(2) at levels
      greater than 20 ppm, have any health effects or indicators of CHD been observed
      consistently? (3) Among occupational groups exposed to CS(2) at levels less than
      20 ppm, have any health effects or indicators of CHD been observed consistently?
      RESULTS: Several CHD-related effects have been examined relative to various
      levels of occupational CS(2) exposure. Overall, there was remarkably little
      consistency of CHD effects observed, including CHD mortality. CONCLUSIONS:
      Although a physiological effect of CS(2) exposure on CHD is plausible, the
      epidemiological evidence for an association between CS(2) exposure and various
      cardiac risk indicators is mixed. The only somewhat consistent finding, of CS(2)
      exposure on total and/or LDL cholesterol level, may be due to residual
      confounding by other time-dependent risk factors. If real, however, it appears to
      be of small magnitude and uncertain clinical importance.

PMID- 12070633
TI  - External and internal dose in subjects occupationally exposed to ochratoxin A.
AB  - OBJECTIVES: Ochratoxin A (OA) is a ubiquitous mycotoxin that can contaminate
      foods, drinks, and animal feeds worldwide. Humans and animals can therefore
      absorb this toxin via the gastrointestinal tract after ingestion of contaminated
      products. OA is known to exert toxic effects, particularly on the renal system,
      and the International Agency for Research on Cancer (IARC) classified it as a
      "possible human carcinogen" (Group 2B). The measurement of OA serum levels is an
      effective method of evaluating internal doses. Inhalation of airborne OA can
      represent a source of additional exposure. We determined the levels of serum OA
      in workers exposed to airborne dust originating from the handling or processing
      of contaminated foods. METHODS: We carried out area and personal sampling for
      airborne OA determination in three industries where coffee, cocoa beans, and
      spices, foods highly susceptible to contamination, were being processed. OA
      levels in the serum of six healthy workers employed in these factories were
      measured in samples collected at the end of the work shift. RESULTS: Airborne OA
      measured in the three industries, both by personal and area sampling, ranged from
      < 0.003 to 8.15 ng/m(3), while the levels measured in the breathing zone of the
      six workers who agreed to biological monitoring varied from 0.006 to 0.087
      ng/m(3). OA serum levels ranged from 0.94 to 3.28 ng/ml, the latter values rather
      largely exceeding those of the control group (0.03 to 0.95 ng/ml). CONCLUSIONS:
      Our findings suggest that occupational exposure to this mycotoxin may represent a
      health risk for workers, especially if preventive and protection measures are not
      adopted in the workplaces. Airborne exposure levels can result in an increase of
      OA levels in serum, and this finding suggest that environmental and biological
      monitoring should be undertaken in workplaces where OA-contaminated products are
      handled or processed.

PMID- 12070634
TI  - Toluene, xylenes and xylene isomers in urine as biological indicators of low
      level exposure to each solvent; a comparative study.
AB  - OBJECTIVE: To examine if xylenes and xylene isomers in end-of-shift urine are
      good biological indicators of low-level exposure to each solvent, similarly to
      toluene in urine. METHODS: The study was conducted in the latter half of a
      working week. Furniture makers, 86 subjects in total (76 men and ten women),
      participated in the study in combination with 11 non-exposed subjects. Time
      weighted average (8-h TWA) exposures to mixtures of toluene (TOL-A), xylenes
      (XYLs-A), ethylbenzene (EB-A), acetone (ACE-A) etc. were monitored with diffusive
      samplers for lipophilic and hydrophilic solvents, respectively. Urine samples
      (i.e., TOL-U, XYLs-U, EB-U, ACE-U, etc.) were collected at the end of the shift
      and subjected to head-space gas chromatography analysis for each solvent. The
      exposure-excretion relationship was examined by simple as well as multiple
      regression analysis. RESULTS: The exposures to TOL and XYLs were around or below
      current occupational exposure limit levels. The exposures to other solvents
      [i.e., ACE, EB, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), etc.]
      were at substantially lower levels. The correlation of the TWA solvent exposure
      concentration with the concentration of the corresponding solvent in the end-of
      shift urine sample was close for TOL, and also almost equally close in the case
      of XYLs and each of the three XYL isomers. Whereas the slope of the regression
      line for XYLs was significantly less steep than that for TOL when compared on an
      equi-molar basis, there was no difference among the three XYL isomers. No
      confounding effects of age, sex and co-exposure to other solvents were detected.
      The observation confirms previous reports that TOL-U is a good marker of TOL
      vapor exposure, indicates that XYL-U is also a reliable marker of exposure to
      vapors of XYLs or any of the three XYL isomers, and suggests that estimation of
      exposure to vapors of XYLs (i.e., three isomers in combination) is possible by
      the determination of one of the XYL isomers in urine, once the proportion of the
      isomers in air is known. Possible association of water solubility with solvent
      levels in urine is discussed. CONCLUSIONS: Biological monitoring of exposure by
      means of analysis of end-of-shift urine for mother solvent is possible, not only
      in the case of TOL as previously reported, but also in cases of XYLs, either for
      three isomers in combination or separately.

PMID- 12070635
TI  - Reduced cognitive abilities in lead-exposed men.
AB  - OBJECTIVES: Since it is still controversial whether-low-to moderate long-term
      lead exposure below current threshold values causes neurobehavioural deficits in
      adults, we investigated executive functions of the prefrontal cortex, attention,
      and visuospatial and visuomotor functioning in lead-exposed subjects. METHODS:
      Forty-seven lead-exposed subjects with a mean blood lead (PbB) level of 30.8
      microg/100 ml and 53 non-lead-exposed aged-matched subjects (PbB: 4.32 microg/100
      ml) with the same socio-economic background were investigated. Both groups were
      also matched on verbal intelligence. Neuropsychological tests were done by the
      modified Wisconsin card sorting test, block design test, visual recognition test,
      simple reaction time, choice reaction and digit symbol substitution. Lead
      exposure was assessed by current and cumulative measures. RESULTS: While there
      were significant differences in the results of the Wisconsin, block design and
      visual recognition tests, no differences were found in simple reaction time,
      choice reaction and digit symbol substitution. Significant correlations existed
      between current exposure and cognitive deficits. No correlation was found between
      cumulative exposure measures and cognitive parameters. CONCLUSIONS: Our results
      show that PbB below 70 microg/100 ml reduce neurobehavioural abilities,
      particularly visuospatial abilities and executive functions referring to the
      prefrontal cortex. As neurobiological substrate of the prefrontal dysfunction,
      glutamatergic system disturbances are discussed.

PMID- 12070636
TI  - Changes in n-hexane toxicokinetics in short-term single exposure due to co
      exposure to methyl ethyl ketone in volunteers.
AB  - OBJECTIVES: Animal studies demonstrate that the formation of the neurotoxic
      metabolite, 2,5-hexanedione (HD) decreases during co-exposure to methyl ethyl
      ketone (MEK). The aim of the present study was to describe the influence of co
      exposure to MEK on n-hexane toxicokinetics in humans. METHODS: Four healthy male
      volunteers were exposed, on different occasions, to three different combinations
      of vapor of these solvents, namely: 50 ppm n-hexane alone, and in combination
      with 100 and 200 ppm MEK, for 2 h during light physical exercise (50 W).
      Arterialized capillary blood, venous blood, and urine were sampled at scheduled
      intervals before, during, and up to 24 h after the onset of the exposure. HD in
      venous blood and urine was analyzed by gas chromatography with electron capture
      detector after derivatization with O-(pentafluorobenzyl) hydroxylamine. RESULTS:
      Serum HD decreased with increasing exposure to MEK at 2 h after the onset of the
      exposure, from an average concentration of 2.2 micromol/l in the n-hexane-alone
      condition to 1.2 and 0.44 micromol/l in the 100 and 200-ppm MEK conditions,
      respectively. The area under the concentration-time curve of HD in venous blood
      and the concentration of HD at 2 and 4 h after the end of exposure decreased with
      increasing MEK. These results suggest that combined exposure to MEK and n-hexane
      at occupationally realistic levels depresses the metabolism of n-hexane in a dose
      dependent fashion. CONCLUSION: The internal exposure to the toxic metabolite of n
      hexane decreased with co-exposure to MEK in a dose-dependent fashion. Estimation
      of external exposure by HD in serum or urine could be confounded by the co
      exposure to MEK.

PMID- 12070637
TI  - Predictors of herbicide exposure in farm applicators.
AB  - OBJECTIVES: Most epidemiological studies of pesticides have used self-reports
      rather than quantitative measurements to assess exposures. The purpose of this
      study was to identify factors likely to affect exposure under actual field
      conditions and to measure the sensitivity and specificity of self-reported
      indications of exposure against urinary measures of herbicide exposure. METHODS:
      A sub-set of the participants in a retrospective cohort study of Ontario farm
      families volunteered for a pesticide exposure assessment study. Immediately
      prior, and subsequent to, handling the phenoxy-herbicides 2,4
      dichlorophenoxyacetic acid (2,4-D) or 4-chloro-2-methylphenoxyacetic acid (MCPA)
      for the first time during the season, 126 pesticide applicators provided pre
      exposure spot urine samples and a subsequent consecutive 24-h urine sample. At
      the same time, they completed a questionnaire on pesticide use and handling
      practices for the first day of pesticide application. RESULTS: Assuming that the
      presence of 2,4-D in the urine was a measure of true exposure and that
      questionnaire indications of 2,4-D use were the exposure classification subject
      to error, then the questionnaire's prediction of exposure had a sensitivity of
      56.7% and specificity of 86.4%. The comparable values for MCPA were sensitivity
      and specificity of 91.6% and 67.4%, respectively. In multivariate models, the
      variables pesticide formulation, protective clothing/gear, application equipment,
      handling practice, and personal hygiene practice were significant as predictors
      of urinary herbicide levels in the first 24 h after application (or spraying) had
      been initiated (adjusted R(2)=44% for MCPA and 39% for 2,4-D). CONCLUSIONS:
      Although similar domains of factors were associated with exposure in both models,
      the specific factors identified and the signs of the coefficients were
      sufficiently different between the final models for each herbicide that
      additional investigations appear to be warranted to determine the sources of the
      differences and assess the validity of the models and their ability to be
      generalised.

PMID- 12070638
TI  - Concepts in developing health-based indicators for ozone.
AB  - OBJECTIVES: The traditional manner to evaluate whether regulatory controls meet
      their public health goals of reducing adverse health effects associated with
      exposure to environmental pollutants is to compare measured concentrations of the
      target pollutant in the environment with a standard. A complementary approach is
      also to measure health-based indicators, e.g., changes in the prevalence of
      adverse health outcomes attributed to the pollutant. This manuscript presents the
      concepts of using asthma emergency room (ER) visits and hospital admission as
      potential health-based indicators for ozone. METHODS: The frequency of ER visits
      and hospital admissions for asthma in New Jersey in 1995 was compared with daily
      ozone concentrations, to establish the consistency of the relationship and the
      presence of potential confounders, and to establish whether routinely documented
      adverse outcomes in asthmatics could serve as health-based indicators. RESULTS: A
      mathematical model relating ER visits and hospital admissions of asthmatics to
      ozone concentration was developed for 1995, which was to be used as a baseline
      year within a health-based indicator program. A coherent relationship was found
      between same-day ambient air ozone concentrations and ER visits and 2-day time
      lagged ambient ozone and hospital admissions during 1995; pollen was identified
      as a confounder and the association between ER visits and ozone concentration was
      similar to that determined for 1986 to 1990. CONCLUSIONS: Sufficient databases
      exist for ER visits by asthmatics in Northern and Central New Jersey, and
      throughout the state for hospital admissions, for these health outcomes to be
      used as health-based indicators, complementing air-monitoring data in assessing
      whether improvements in public health are occurring because of reduction in
      emissions of precursors of ozone.

PMID- 12070639
TI  - Occupational relevance of positive standard patch-test results in employed
      persons with an initial report of an occupational skin disease.
AB  - OBJECTIVES: It is commonly accepted that the standard screening tray is an
      essential diagnostic test in patch testing supporting the diagnosis of contact
      dermatitis, the most common type of occupational skin disease (OSD). In this
      study standard patch-test results of employed persons with an initial report of
      an OSD were analyzed within 24 occupational groups. METHODS: An evaluation was
      made of employed persons recorded in the Register of Occupational Skin Diseases
      in Northern Bavaria (Berufskrankheitenregister Haut-Nordbayern; BKH-N) between
      1990 and 1999, catering for those standard screening tray allergens tested over
      the 10-year period. RESULTS: Nickel sulfate was the most common sensitizer
      (29.5%), showing occupational relevance in only 11% of the cases sensitized.
      Other common sensitizers were cobalt chloride (13.5%), p-phenylenediamine free
      base (10.7%), potassium dichromate (9.8%), fragrance mix (5.4%), thiuram mix
      (4.2%), balsam of Peru (4.0%), chloromethylisothiazolinone/methylisothiazolinone
      (4.0%), and formaldehyde (4.0%). The most occupationally relevant sensitizers
      were thiuram mix (71%), epoxy resin (67%), p-phenylenediamine free base (59%), p
      phenylenediamine-black-rubber mix/ N-isopropyl- N'-phenyl- p-phenylenediamine
      (53%), potassium dichromate (48%), formaldehyde (38%),
      chloromethylisothiazolinone/methylisothiazolinone (37%), and mercapto
      mix/mercaptobenzothiazole (35%). Occupational groups at risk of acquiring delayed
      type sensitization were, in particular, electroplaters, tile setters and terrazzo
      workers, construction and cement workers, solderers, wood processors, and leather
      and fur processors. CONCLUSIONS: The standard series contributes valuable
      information and asserts its position in clarifying the causes of OSDs. Based on
      the study results, the rate of occupationally relevant sensitization to each
      single allergen is demonstrated, and the difficulties in verifying the
      occupational relevance are discussed.

PMID- 12070640
TI  - Disturbed sleep-wake patterns during and after short-term international travel
      among academics attending conferences.
AB  - OBJECTIVES: To examine variations in sleep and wakefulness associated with
      international travel. METHODS: Ten academics in Japan were studied while
      traveling abroad to participate in conferences. Wrist activity and a daily log
      were recorded continuously for 1 week before, during, and for 1 week after
      travel. Destinations included the USA and Canada to the east (8 to 11-h time
      difference; mean stay of 6.8 days) and Europe to the west (7 to 8-h time
      difference; mean stay of 6.0 days). RESULTS: For eastward-traveling subjects, the
      total sleep time was shorter and the mean activity during sleep was greater at
      the destinations than before departure. These sleep disruptions persisted until
      the 2nd day after the subjects had returned home. The sleep patterns then
      recovered in a zigzag manner. No significant disruptions in the main sleep were
      found in westward travelers, although these subjects took a longer nap
      immediately after their return. The beginning and end of sleep occurred earlier
      until the 2nd day after the subjects had returned from eastward trips, but
      occurred later until the 5th day after return from westward trips. CONCLUSIONS:
      In academics, short-term international travel causes sleep disturbances both
      during and at home after eastward travel and a delay in the sleep timing at home
      after westward travel. Although the subjects in this study might be atypical of
      business travelers, the current data suggest that strategies are needed to
      facilitate recovery from disturbed sleep-wake patterns at home after travel,
      i.e., redesign of post-travel work schedules.

PMID- 12070641
TI  - Proteolytic enzyme sensitivity and decrease in respiratory function (a 10-year
      follow-up).
AB  - OBJECTIVES: In workers, sensitivity and occupational asthma are known to develop
      in reaction to the proteolytic enzymes used in the manufacture of detergents.
      This study was conducted to find out how this sensitivity to the proteolytic
      enzymes affects respiratory function, excluding occupational asthma. METHODS:
      Workers in the detergent industry ( n = 65) were divided into four groups
      according to their prick-test results, as follows: those positive for at least
      one enzyme (Lipolase, Savinase) (group I, n = 15); enzyme-negative cases (group
      II, n = 50); and from among these, enzyme-positive non-smoking cases (group Ia, n
      = 11); enzyme-negative non-smoking cases (group IIa, n = 32). Respiratory
      function tests for the last 10 years from the archives were assessed. For
      statistic analysis, average values were determined and the standard deviation
      calculated. For comparison of the groups, the Mann-Whitney U and Fischer Exact
      chi-square tests were used. RESULTS: The ratio of smokers, the cigarette burden,
      average age and the period of work were found to be similar between workers of
      groups I and II, and group Ia and group IIa ( P > 0.05). The average annual fall
      in the forced vital capacity (FVC) and the forced expiratory volume in the first
      second (FEV(1)) for the 10-year period was, respectively, found to be: group I,
      64.1 +/- 7.8 ml and 58.7 +/- 9.6 ml; group II, 38.7 +/- 6.4 ml and 43.7 +/- 8.2
      ml; group Ia, 60.7 +/- 8.1 ml and 56.1 +/- 10.2 ml; group IIa, 37.4 +/- 6.8 ml
      and 42.9 +/- 8.1 ml. The decrease in FVC and FEV(1) in group I compared with
      group II, and in group Ia compared with group IIa was statistically significant (
      P < 0.001). CONCLUSIONS: In this study, the observation that the FVC and FEV(1)
      of the workers were much lower than expected, especially among those sensitive to
      the enzymes, independently of occupational asthma and cigarette smoking, led to
      the conclusion that it could be due to sensitivity to the enzymes.

PMID- 12070642
TI  - Surgery of skeletal metastases.
AB  - During a period of 5 years, 74 female and 27 male patients with an average age of
      63.3 years underwent a total of 117 operations for the management of impending (
      n=41) or already existing ( n=76) pathologic fractures due to osseous metastases.
      The average stay in hospital was 17.8 days, and the average postoperative
      survival 15.8 months. The patients whose limbs were stabilized as a preventive
      measure were discharged 1.5 days earlier and survived surgery 5.9 months longer
      than the patients with pathologic fractures. The large percentage of female
      patients is due to the predominant role of mammary cancer (50%) and the
      comparatively long survival of patients after a primary diagnosis of this type of
      carcinoma. The other diagnoses involved were (in order of frequency): bronchial
      carcinoma (11%), hypernephroma (8%) and non-Hodgkin's lymphoma (8%). The
      metastases were mainly located at the proximal end or shaft of the femur (59.8%)
      and in the humerus (18.8%) so that in the majority of cases it was possible to
      implant weight-bearing prostheses or at least achieve enough stability to allow
      non-weight-bearing physiotherapy and thus early remobilization. The rate of
      systemic complications (excluding fatalities) was 14.5%. Local complications in
      the operated area occurred in 24.8% of cases. As a result, revision surgery was
      necessary in 10 cases (8.5%), and the fatality rate in hospital (6 weeks) was
      7.9%. In view of the advanced stage of the disease in most of the patients, some
      of them with polypathia, we see these results as a basis for the generous
      indication for preventive stabilization of osseous metastases. Except in some
      cases, the primary intention of this therapy is not to cure the disease or
      prolong life but to improve the quality of life remaining for these patients
      while keeping their stay in hospital as short as possible and the rate of
      complications at an acceptable level.

PMID- 12070643
TI  - Efficacy of primary wound cultures in long bone open extremity fractures: are
      they of any value?
AB  - The management of long bone open extremity fractures has included initial wound
      cultures, antibiotics, operative debridement, and fracture repair, if indicated.
      The value of initial wound cultures is unclear. We examined whether primary wound
      cultures predict which wounds will become infected, and whether bacterial growth
      on primary wound cultures correlates with bacteria cultured from infected wounds.
      This prospective study involved patients presenting to a regional trauma center.
      Before any interventions were performed, initial aerobic and anaerobic cultures
      of the wounds of 117 consecutive open extremity fractures grades I-III were
      obtained. The results of these cultures were correlated with the development of a
      wound infection, and if an infection occurred, the organism grown from the
      infected wound was compared with any organism grown from the primary wound
      cultures. Of the initial cultures, 76% (89/117) did not demonstrate any growth,
      while the other 24% (28/117) only grew skin flora. There were only 7 (6%) wound
      infections, and 71% (5/7) initially did not grow any organisms. Of the isolates
      that grew from the initial cultures, none were the organisms that eventually led
      to wound infections. The use of primary wound cultures in open extremity injuries
      has no value in the management of patients suffering long bone open extremity
      fractures.

PMID- 12070644
TI  - Femoral anatomy, computed tomography and computer-aided design of prosthetic
      implants.
AB  - Precise digital data of the internal femoral anatomy are necessary to develop new
      prosthetic implants with computer-aided design (CAD) techniques. Thirty human
      cadaveric femurs of central European origin were analysed by high precision
      computed tomography (CT) using thin slice and high resolution imaging. The CT
      data were image processed with thresholding to obtain a reconstruction of the
      cortical bone geometry. The CT threshold for cortical bone was optimized by
      comparison with saw cuts of macerated femurs. For each specimen a three
      dimensional (3D) model of the cortical femur was calculated by the CAD system
      based on the processed CT data. Virtual 3D models of the 30 femurs were used to
      adjust a hypothetical stem to the proximal femur anatomy by repeated virtual
      implantations. The CAD system allowed for evaluation of anatomical parameters
      after hip reconstruction, amount of bone removal, and cortical bone contact. The
      fit and fill of the stem could be tested before clinical application and implant
      related problems could be corrected.

PMID- 12070645
TI  - Influence of acid-citrate-dextrose anticoagulant on blood quality in
      retransfusion systems after total knee arthroplasty.
AB  - The influence of acid-citrate-dextrose (ACD) anticoagulant on the blood quality
      was assessed in this prospective, randomized, controlled study. The clinical
      consequences with regard to retransfusion of drainage blood following total knee
      arthroplasty were evaluated. After total knee arthroplasty, retransfusion was
      performed utilizing a "SureTrans" retransfusion system in 81 patients. In 42 of
      them, blood was collected adding an ACD anticoagulant (group A), while in the
      remaining 39 patients blood was collected without any additives (group B). Blood
      losses were retransfused over a 6-h period after attaching the retransfusion
      system to the patient of either group. Blood samples of the 6-h blood collection
      were taken and analysed for several blood quality parameters. Significant
      differences were found in the platelet count (61,200+/-16,700 microl(-1) in group
      A versus 70,100+/-21,600 microl(-1) in group B, p=0.042), the lactate
      concentration (4.09+/-0.86 mmol/l vs 4.82+/-0.83 mmol/l, p<0.001), the pH (6.96+/
      0.10 vs 7.18+/-0.06, p<0.001), as well as the protein content (5.44+/-0.57 g/dl
      vs 5.85+/-0.43 g/dl, p<0.001). These observed significant differences were,
      however, of no clinical relevance to the patients' treatment. Hemoglobin
      concentration, hematocrit, mean corpuscular volume (MCV), erythrocyte count,
      leukocyte count, concentration of free hemoglobin in the blood plasma (fHb),
      potassium concentration, lactate dehydrogenase (LDH), serotonin concentration,
      triglyceride concentration, free fatty acid concentration, and interleukin-6
      concentration did not differ significantly. This study indicates that the blood
      quality in retransfusion systems is not substantially influenced by adding ACD
      anticoagulant.

PMID- 12070646
TI  - Heterotopic ossification around distal femur after total knee arthroplasty.
AB  - Heterotopic ossification after total knee arthroplasty is not well recognized. We
      found heterotopic ossification around the distal femur in 10 (5%) of 221 knees
      after primary total knee arthroplasty and evaluated clinical findings as well as
      risk factors. The duration of follow-up ranged from 1 to 5 years. Most patients
      with heterotopic ossification showed clinical findings that were suspected of
      being early infection after surgery such as continuing low-grade fever and
      erythematous, warm, and swollen knees, whereas blood examinations were normal.
      Heterotopic ossification developed by a mean period of 5 weeks, and the size
      increased for a mean period of 9 weeks. The maximum size of the ossification was
      <5 cm in 9 knees and >5 cm in 1 knee. After that, the size decreased without any
      treatment in all knees, and the ossification finally disappeared in 2 knees.
      Osteoarthrosis and the presence of postoperative effusion were the significant
      risk factors in the development of heterotopic ossification. Although it is
      difficult to draw valid conclusions from our small study, heterotopic
      ossification at the distal femur after total knee arthroplasty needed no
      treatment and was not progressive, nor did it affect the short-term outcome in
      this study.

PMID- 12070648
TI  - Cobalt and chromium concentrations in patients with metal-on-metal and other
      cementless total hip arthroplasty.
AB  - We measured the cobalt and chromium concentrations in the serum and urine of 32
      patients with current designed metal-on-metal total hip arthroplasty and 43
      patients with conventional metal on ultrahigh molecular weight polyethylene
      (UHMWPE) cementless total hip arthroplasty. The results of our study showed that
      the serum and urine chromium concentrations increased in 37.5% and 90.6%,
      respectively, of 32 patients with well-fixed metal articulation (the mean values
      were 0.09 microg/dl and 2.2 microg/l, respectively) and also increased in 28.6%
      and 85.7%, respectively, of 7 patients who received metal-on-UHMWPE articulation
      with loosened acetabular component or stem made of Co/Cr alloy (the mean values
      were 0.06 microg/dl and 1.6 microg/l, respectively). On the other hand, the serum
      and urine cobalt concentrations were below the detection limit in all patients.

PMID- 12070647
TI  - Bone turnover during distraction osteogenesis in an experimental sheep model.
AB  - Biochemical serum markers of osteoblastic activity and collagen turnover were
      measured in a sheep model of distraction osteogenesis. Significant increases of
      the bone formation marker osteocalcin were found during the first part of the
      consolidation phase and peaked at a time point equalling the distraction phase.
      Collagen turnover parameters pyridinoline and the specific type I collagen marker
      desoxypyridinoline consistently increased during the distraction and
      consolidation phases. While pyridinoline peaked at a time point similar to
      osteocalcin, desoxypyridinoline increased to a later stage in consolidation,
      indicating continuous turnover of bone-specific type I collagen. The results
      indicate a characteristic pattern of osteoblast cellular activation during
      distraction osteogenesis with possible consequences for the timing of treatment.

PMID- 12070649
TI  - Transfemoral approach for revision total hip arthroplasty.
AB  - We performed revision total hip arthroplasty on 12 patients via the transfemoral
      approach because difficulty with surgery was anticipated preoperatively. The
      total hip score improved in all of the patients. Radiographically, there were no
      radiolucent lines around the acetabular and femoral components, but one hip still
      showed sinking of the stem by 2 cm. Although the transfemoral approach might seem
      very aggressive, this is actually a relatively simple method that allows rapid
      removal of the prosthesis and cleaning of the medullary canal.

PMID- 12070650
TI  - Bone remodelling along a titanium hip arthroplasty stem after resection of a
      chondrosarcoma.
AB  - Long-term anchorage of cementless total hip arthroplasty relies on a direct bone
      to implant bonding. Several factors including material properties and surface
      treatment determine the interfacial response of the host bone to a foreign
      material. In the case presented, a chondrosarcoma of the proximal femur required
      an extended extraperiosteal resection. Reconstruction was possible with a
      titanium-alloy revision stem. A bony remodelling of the proximal femur was
      observed along the surface of the stem.

PMID- 12070651
TI  - Distraction of hypertrophic nonunion of tibia with deformity using
      Ilizarov/Taylor Spatial Frame. Report of two cases.
AB  - Two cases of hypertrophic nonunion of the tibia with deformity for which
      distraction treatment using an Ilizarov/Taylor Spatial Frame (Smith & Nephew,
      Memphis, TN) are presented. This frame utilizes a computer program to help plan
      correction of the deformity.

PMID- 12070652
TI  - Japanese acrylic hemi-arthroplasty of the hip with a 45-year follow-up without
      revision.
AB  - We report the case of a patient who underwent acrylic hemi-arthroplasty of the
      hip and survived 45 years without revision. The patient had undergone hemi
      arthroplasty of the hip at the age of 17 years following failure of a previous
      hemi-arthroplasty at the age of 12 years. We saw her 45 years later and carried
      out physical examination, standard radiographs of the hip as well as computed
      tomography. In addition, we reviewed the literature concerning the acrylic
      prosthesis and discussed the reasons for long-term durability.

PMID- 12070653
TI  - Slipped capital femoral epiphysis in osteopetrosis: an unusual case.
AB  - We report on a 9-year-old boy who has type II autosomal dominant osteopetrosis
      associated with a chronic grade II slipped capital femoral epiphysis. He was
      treated with a single cannulated screw. This rare association has been reported
      only once.

PMID- 12070654
TI  - Ruptured abdominal aortic aneurysm associated with a psoas abscess.
AB  - A case of abdominal aortic aneurysm infected by Salmonella dublin is presented.
      Computed tomography (CT) revealed an abdominal aortic rupture associated with a
      psoas abscess. An axillo-femoral bypass was performed. The aneurysm and the psoas
      abscess were resected.

PMID- 12070655
TI  - Rare presentation of non-Hodgkin lymphoma of the thoracolumbar spine in pregnancy
      with 7 years' survival.
AB  - A rare, so far unpublished, case of non-Hodgkin lymphoma in 26-year-old pregnant
      woman is presented. As X ray examination and other investigations were avoided
      during her pregnancy, the discrete signs of spinal cord compression led to sudden
      severe neurological deterioration after delivery. This necessitated emergency
      decompression and stabilization of the spine. Acute surgical treatment resulted
      in complete functional recovery. It was followed by chemotherapy and
      radiotherapy, which led to disease-free survival 7 years after the surgery.
      Magnetic resonance imaging is the examination of choice when long-lasting back
      pain during pregnancy does not resolve with bed rest.

PMID- 12070656
TI  - Brodie's abscess of the proximal femoral epiphysis in an adult woman with
      systemic lupus erythematosus.
AB  - We report an unusual case of pathologically proved femoral head Brodie's abscess
      mimicking avascular necrosis of bone in a 51-year-old woman with a 2-year history
      of corticosteroid treatment for systemic lupus erythematosus. On plain
      radiographs, a rounded lucency and thin sclerotic margins together with
      subchondral collapse and a lytic region were observed in the femoral head. The
      histopathologic examination revealed a central abscess formation surrounded by
      fibrous tissue with the aggregation of neutrophils and plasma cells. To our
      knowledge, this is the first case report describing a Brodie's abscess which had
      developed within the proximal femoral epiphysis in an adult.

PMID- 12070657
TI  - Caspase-cleaved amyloid precursor protein and activated caspase-3 are co
      localized in the granules of granulovacuolar degeneration in Alzheimer's disease
      and Down's syndrome brain.
AB  - Granulovacuolar degeneration (GVD) is a diagnostic neuropathological feature of
      Alzheimer's disease (AD). In some neurons, apoptosis has been hypothesized to be
      a primary mechanism causing neuronal cell death in AD. In this study we
      investigated CA1 neurons with GVD in AD and Down's syndrome (DS) brain. We
      demonstrated that activated caspase-3 and a caspase-cleaved cleavage product of
      the amyloid precursor protein (cAPP) are co-localized in GVD granules, and that
      these same cells often show nuclear DNA damage. In contrast, activated caspase-8
      is present in the cytoplasm but not within the granules of GVD neurons. A caspase
      cleavage product of fodrin that accumulates in many AD and DS neurons is not
      present in GVD granules. These data support a role for the activation of
      apoptotic mechanisms in selective compartments exhibiting GVD.

PMID- 12070659
TI  - Brain stem lesions in the sudden infant death syndrome: variability in the
      hypoplasia of the arcuate nucleus.
AB  - In the present study we investigated quantitatively the incidence of hypoplasia
      of the arcuate nucleus (ARCn) of the medulla oblongata, reported earlier [Gozal
      D, Hathout GM, Kirlew KAT (1994) J Appl Physiol 76:207], as well as its
      distribution in 62 cases of sudden infant death syndrome (SIDS; mean age 14
      postnatal weeks, 39 male and 23 female) and 25 controls (mean age 16 postnatal
      weeks, 14 male and 11 female), using detailed histopathological and morphometric
      analyses performed on serial sections of medulla oblongata. The SIDS cases were
      divided into four subtypes: SIDS A (27 cases, 43%) with histologically well
      developed ARCn; SIDS B (16 cases, 26%) with severe bilateral hypoplasia along the
      whole length; SIDS C (11 cases, 18%) with partial bilateral hypoplasia, located
      mainly in the lateral portions of the caudal two thirds of the nucleus, and SIDS
      D (8 cases, 13%) with right monolateral hypoplasia of the ARCn. ARCn hypoplasia
      was detected in 56% of cases (35 cases). Three-dimensional volume reconstruction
      showed that in the SIDS A victims the mean volume was analogous to controls,
      whereas in the SIDS group with ARCn hypoplasia, severe or partial, the mean
      volume was significantly different from controls on both sides of the medulla
      oblongata (SIDS B group: P=0.003, P=0.002; SIDS C group: P=0.007, P=0.008). The
      mean ARCn volume in the SIDS D group was statistically significant only on the
      right side ( P=0.005). We also observed reduced neuron density of the ARCn,
      associated with a decrease in the total number of neurons over the whole length
      of the nucleus itself. On the basis of the morphometric results of neuronal
      population in the different portions of the ventrolateral medulla in SIDS cases,
      we hypothesized that infants without the full complement of neurons and neuropil
      (ARCn hypoplasia) are at risk for SIDS because they are unable to develop
      appropriate cardioventilatory control during this crucial developmental period.

PMID- 12070658
TI  - Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred.
AB  - Previous genetic analysis of the familial Parkinson's disease Contursi kindred
      led to the identification of an Ala53Thr pathogenic mutation in the alpha
      synuclein gene. We have re-examined one of the original brains from this kindred
      using new immunohistochemical reagents, thioflavin S staining and immunoelectron
      microscopy. Surprisingly, we uncovered a dense burden of alpha-synuclein neuritic
      pathology and rare Lewy bodies. Immunoelectron microscopy demonstrated fibrillar
      alpha-synuclein-immunoreactive aggregates. Unexpected tau neuritic and less
      frequent perikaryal inclusions were also observed. Some inclusions were comprised
      of both proteins with almost complete spatial disparity. We suggest that it is
      important to recognize that the neurodegenerative process caused by the Ala53Thr
      mutation in alpha-synuclein is not identical to that seen in typical idiopathic
      Parkinson's disease brains.

PMID- 12070660
TI  - Morphometrical reappraisal of motor neuron system of Pick's disease and
      amyotrophic lateral sclerosis with dementia.
AB  - The conventional concept of Pick's disease does not distinguish Pick's disease
      with Pick bodies (Pick body disease, PBD) from Pick's disease without Pick bodies
      [lobar atrophy without Pick bodies, LA-PB(-)]. Recently, intraneuronal ubiquitin
      positive inclusions (ub-inclusions), which are thought to be a hallmark of
      amyotrophic lateral sclerosis with dementia (ALS-D), have been found also in LA
      PB(-). We reconfirmed that ub-inclusions are consistently detected in LA-PB(-) as
      well as ALS-D. Subsequently, morphometric evaluation for involvement of the upper
      and lower motor neuron systems were performed in seven cases each of PBD, LA-PB(
      ), ALS-D and controls. As an indicator of upper motor neuron involvement, the
      total number of axons through the pyramis of the medulla oblongata was employed
      and for lower motor neuron involvement, the number of hypoglossal neurons per
      unit area was calculated. In LA-PB(-), axons of the pyramidal tract were
      significantly reduced in comparison to PBD and controls, while the lower motor
      neurons were preserved. Contrary to LA-PB(-), ALS-D revealed significant
      reduction of hypoglossal neurons but its pyramidal tract tends to be relatively
      preserved. These results seem to indicate that LA-PB(-) and ALS-D belong to the
      same spectrum and consist of subgroups with ub-inclusions and involvement of
      motor neuron system in common. The involvement of the upper motor neuron system
      is emphasized in LA-PB(-), while ALS-D accentuates the lower motor neuron system.
      However, the border between the two group is not always clear and there are
      patients who can not be definitively classified.

PMID- 12070662
TI  - Cellular distribution of proteolytic enzymes in the skeletal muscle of sarcoid
      myopathy.
AB  - To clarify the mechanism of muscle fiber destruction in sarcoid myopathy, muscle
      biopsy specimens were examined from patients with sarcoid myopathy, polymyositis,
      or dermatomyositis. In sarcoid myopathy, noncaseating granulomatous lesions were
      located in the perimysium or endomysium or both. Little fiber atrophy, caused by
      mechanical compression of the granuloma, was seen, and there was no evidence of
      ischemia-induced changes (i.e., perifascicular atrophy) due to microangiopathy in
      muscles. Immunoreactivity for membrane-associated cytoskeletal proteins such as
      dystrophin and merosin was detected homogeneously along the surface of many small
      granulomas in intrafascicular lesions. These granulomas showed a characteristic
      phenotypic cellular distribution: CD68(+) and CD4(+) cells were present in the
      center, and some CD8(+) cells were found at the periphery, indicating typical
      sarcoid granuloma formation in each muscle fiber. Strong expression of proteases
      such as cathepsin B, calpain II and ubiquitin-proteasome was observed in
      macrophages and epithelioid cells but not in lymphocytes in granulomas within
      muscle fibers or those in the endomysium or perimysium. The expression intensity
      was stronger in premature-stage granulomas than in late-stage granulomas. Weak
      expression of these proteases was detected mainly in some muscle fibers invaded
      by epithelioid cells and macrophages and in a few atrophic or necrotic fibers
      adjacent to inflammatory foci but not in fibers of fascicles without granuloma
      formation or in fibers in perifascicular areas. Our results suggest that muscle
      fiber destruction in sarcoid myopathy is caused mainly by direct invasion of
      granulomatous inflammatory cells into muscle fibers during the process of
      granuloma formation rather than by mechanical compression or ischemia.
      Furthermore, the proteases derived from epithelioid cells and macrophages may
      play an important role in muscle fiber destruction.

PMID- 12070661
TI  - Expression of ataxin-7 in CNS and non-CNS tissue of normal and SCA7 individuals.
AB  - Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder primarily
      affecting the cerebellum, brain stem and retina. The disease is caused by an
      expanded polyglutamine tract in the protein ataxin-7. In this study we analyzed
      the expression pattern of ataxin-7 in CNS and non-CNS tissue from three SCA7
      patients and age-matched controls. SCA7 is a rare autosomal dominant disorder,
      limiting the number of patients available for analysis. We therefore compiled
      data on ataxin-7 expression from all SCA7 patients (n=5) and controls (n=7)
      published to date, and compared with the results obtained in this study.
      Expression of ataxin-7 was found in neurons throughout the CNS and was highly
      abundant in Purkinje cells of the cerebellum, in regions of the hippocampus and
      in cerebral cortex. Ataxin-7 expression was not restricted to regions of
      pathology, and there were no apparent regional differences in ataxin-7 expression
      patterns between patients and controls. The subcellular distribution of ataxin-7
      was primarily nuclear in all brain regions studied. In cerebellar Purkinje cells,
      however, differences in subcellular distribution of ataxin-7 were observed
      between patients and controls of different ages. Here we provide an increased
      understanding of the distribution of ataxin-7, and the possible implication of
      subcellular localization of this protein on disease pathology is discussed.

PMID- 12070663
TI  - N(epsilon)-Carboxymethyllysine in diabetic and non-diabetic polyneuropathies.
AB  - Increased oxidative stress and advanced glycosylation are important factors in
      the development of diabetic neuropathy. In non-diabetic neuropathies their
      influence has not been investigated in detail so far. We studied the localisation
      of N(epsilon)-carboxymethyllysine (CML) - a biomarker for oxidative stress - by
      immunohistochemistry in sural nerve biopsies of 31 patients with different
      polyneuropathies [diabetic polyneuropathy (n=5), alcohol-associated
      polyneuropathy (n=4), vitamin B12-deficient polyneuropathy (n=6), chronic
      inflammatory demyelinating polyneuropathy (CIDP) (n=6), vasculitic neuropathy
      (n=6), Charcot-Marie-Tooth disease type I (CMT I) (n=4)] and 4 normal controls.
      CML was detected in the perineurium of patients with diabetic, alcohol
      associated, vitamin B12-deficient and vasculitic polyneuropathies. Epineurial,
      perineurial and endoneurial vessels were CML positive in diabetic, vitamin B12
      deficient and vasculitic polyneuropathies. CML was also found in mononuclear
      inflammatory cells in vasculitic neuropathy. In CIDP and normal controls there
      was only marginal perineurial CML deposition in 2/6 and 1/4 cases. In CMT I no
      CML was detected. Immunohistochemical results were confirmed by immunoblot. Our
      data suggest a role of oxidative stress in the pathogenesis not only of diabetic
      but also of alcohol-associated, vitamin B12-deficient and vasculitic
      polyneuropathies. It may be a minor pathogenetic factor in CIDP and may not be
      involved in CMT I. Underlying causes for increased oxidative stress may be an
      elevated production of reactive oxygen species and an impairment of antioxidative
      defences. Therefore, an antioxidative treatment should be considered in alcohol
      associated, vitamin B12-deficient and vasculitic polyneuropathy.

PMID- 12070664
TI  - Ballooned neurons in progressive supranuclear palsy are usually due to concurrent
      argyrophilic grain disease.
AB  - Progressive supranuclear palsy (PSP) is a sporadic multisystem neurodegenerative
      disorder that is one of the major causes of parkinsonism, which shares common
      biochemical and genetic features with corticobasal degeneration (CBD). Ballooned
      neurons (BN) are one of the histopathologic hallmarks of CBD and their presence
      is a neuropathologic feature that helps differentiate PSP from CBD, since BN are
      uncommon in PSP. There are, however, several reports in the literature of BN in
      PSP. BN are also a consistent finding in argyrophilic grain disease (AGD), where
      they are relatively confined to limbic structures, in particular the amygdala.
      Since AGD has been found with increased frequency in PSP, it is possible that
      cases of PSP with BN may represent co-existing AGD. In the present study, we
      investigated this possibility by studying the distribution and the density of BN
      with alphaB-crystallin immunostaining in 20 cases of PSP, including equal numbers
      of cases with and without co-existing AGD. In PSP cases with concurrent AGD, BN
      were consistently found in limbic areas, but in pure PSP cases, BN were rare,
      supporting the hypothesis that concurrent AGD may account for most cases of PSP
      with BN.

PMID- 12070665
TI  - Monoclonal antibody to stage-specific fetal brain 68-kDa glycoprotein (FGP68)
      revealed increased FGP68 expression in human primary brain tumors.
AB  - We have produced a novel rat IgG(2a) monoclonal antibody against a stage-specific
      fetal brain glycoprotein of 68 kDa (FGP68), and succeeded in applying it to
      staining paraffin sections. To gain some insight into the pathobiological
      significance of this FGP68, this monoclonal antibody was used in
      immunohistochemical studies to compare the expression of FGP68 and Ki-67 antigen
      (MIB-1) in 235 primary brain tumors. Approximately half of the glioblastomas
      multiforme (GBMs) (44/75) and anaplastic astrocytomas (9/17) as well as some
      astrocytomas (5/30), medulloblastomas (2/14) and primitive neuroectodermal tumors
      (2/10) had tumor cells that expressed FGP68; however, pilocytic astrocytomas
      (0/7), oligodendrogliomas (0/15), ependymomas (0/6), schwannomas (0/21),
      meningiomas (0/22) and pituitary adenomas (0/18) did not express FGP68. The
      values of the MIB-1 labeling index were statistically higher in GBMs (0.005<
      P<0.01, Wilcoxon rank-sum test) and anaplastic astrocytomas (0.025< P<0.05) that
      expressed FGP68 than in those that did not. Normal brain tissue from 20
      individuals aged 3-75 years was negative for FGP68 and MIB-1. We conclude that
      primary brain tumors express FGP68, one of the oncofetal proteins derived from
      fetal brain, and that FGP68 expression in certain brain tumor cells may depend,
      in part, on proliferation potential. Based on the possibility that the stage
      specific FGP68 plays an important role in brain embryogenesis, some of FGP68
      expressing tumor cells might phylogenetically revert to more primitive cells.

PMID- 12070666
TI  - Electron microscopic abnormalities of skeletal muscle in patients with collagen
      VI deficiency in Ullrich's disease.
AB  - By electron microscopy, we examined the skeletal muscle from two patients with
      Ullrich's disease. One patient had a deletion in the collagen VI alpha 2 gene.
      The muscle biopsy specimens showed no collagen VI immunoreaction, while the
      expression of collagen IV was increased. Collagen VI is a microfibrillar protein
      in the extracellular matrix with cell adhesive properties, and collagen IV is a
      principal component of the basal lamina. Electron microscopy revealed unevenness,
      extension, and folding of the muscle plasma membrane, and showed thickening and
      overproduction of the basal lamina. The data show that type VI collagen is
      certainly one of the important extracellular matrix components maintaining the
      structural integrity of skeletal muscle, and a defect of the collagen VI protein
      causes abnormalities of the muscle plasma membrane, dystrophic muscle changes,
      and up-regulation of collagen IV.

PMID- 12070667
TI  - Consensus neuropathological diagnosis of common dementia syndromes: testing and
      standardising the use of multiple diagnostic criteria.
AB  - The aim of this study was to assess the variation between neuropathologists in
      the diagnosis of common dementia syndromes when multiple published protocols are
      applied. Fourteen out of 18 Australian neuropathologists participated in
      diagnosing 20 cases (16 cases of dementia, 4 age-matched controls) using
      consensus diagnostic methods. Diagnostic criteria, clinical synopses and slides
      from multiple brain regions were sent to participants who were asked for case
      diagnoses. Diagnostic sensitivity, specificity, predictive value, accuracy and
      variability were determined using percentage agreement and kappa statistics.
      Using CERAD criteria, there was a high inter-rater agreement for cases with
      probable and definite Alzheimer's disease but low agreement for cases with
      possible Alzheimer's disease. Braak staging and the application of criteria for
      dementia with Lewy bodies also resulted in high inter-rater agreement. There was
      poor agreement for the diagnosis of frontotemporal dementia and for identifying
      small vessel disease. Participants rarely diagnosed more than one disease in any
      case. To improve efficiency when applying multiple diagnostic criteria, several
      simplifications were proposed and tested on 5 of the original 20 cases. Inter
      rater reliability for the diagnosis of Alzheimer's disease and dementia with Lewy
      bodies significantly improved. Further development of simple and accurate methods
      to identify small vessel lesions and diagnose frontotemporal dementia is
      warranted.

PMID- 12070668
TI  - Incidence of axonal injury in human brain tissue.
AB  - Diffuse axonal injury (DAI) is considered to be the morphological correlate of
      traumatic brain injury as seen in acceleration/deceleration trauma and is
      believed to be the main cause for a poor clinical outcome in the absence of
      detectable intracranial lesions. To estimate the overall incidence of DAI, and
      since most changes are only seen microscopically to rule out whether there is a
      high number of undetected cases, 450 non-selected human brains were examined.
      Samples from two brain areas (pons and cerebrum) were immunostained for beta
      amyloid-precursor-protein (betaAPP), and axonal damage was assessed
      microscopically. Axonal injury was detected in 12% of all cases, but only one
      third had a history of traumatic brain injury. The majority of the positive cases
      were associated with drug intoxication, chiefly due to opiates. betaAPP staining
      was positive in both pons and cerebrum to a much higher extent in intoxication
      than in trauma cases; the latter showing axonal damage mainly in the pons area.
      This may reflect a more generalized pathomechanism in the intoxication group as
      compared to more biomechanical mechanisms in the trauma group. The findings also
      show that various causes may produce diffuse axonal injury and suggest that
      traumatic brain injury is not the only and probably not even the main cause of
      the observed neuropathological changes. A correlation between axonal damage and
      age-related processes could not be shown.

PMID- 12070669
TI  - Extracellular matrix and the blood-brain barrier in glioblastoma multiforme:
      spatial segregation of tenascin and agrin.
AB  - The quality of the blood-brain barrier (BBB), represented mainly by endothelial
      tight junctions (TJ), is now believed to be dependent on the brain
      microenvironment and influenced by the basal lamina of the microvessels. In the
      highly vascularized glioblastoma multiforme (GBM), a dramatic increase in the
      permeability of blood vessels is observed but the nature of basal lamina
      involvement remains to be determined. Agrin, a heparan sulfate proteoglycan, is a
      component of the basal lamina of BBB microvessels, and growing evidence suggests
      that it may be important for the maintenance of the BBB. In the present study, we
      provide first evidence that agrin is absent from basal lamina of tumor vessels if
      the TJ molecules occludin, claudin-5 and claudin-1 were lacking in the
      endothelial cells. If agrin was expressed, occludin was always localized at the
      TJ, claudin-5 was frequently detected, whereas claudin-1 was absent from almost
      all vessels. Furthermore, despite a high variability of vascular phenotypes, the
      loss of agrin strongly correlated with the expression of tenascin, an
      extracellular matrix molecule which has been described previously to be absent in
      mature non-pathological brain tissue and to accumulate in the basal lamina of
      tumor vessels. These results support the view that in human GBM, BBB breakdown is
      reflected by the changes of the molecular compositions of both the endothelial TJ
      and the basal lamina.

PMID- 12070670
TI  - Calpain activation in neurodegenerative diseases: confocal immunofluorescence
      study with antibodies specifically recognizing the active form of calpain 2.
AB  - The calcium-activated protease calpain cleaves a variety of biologically
      important proteins and serves, therefore, as a key regulator of many cellular
      functions. Activation of both main isoforms, calpain 1 and calpain 2, was
      demonstrated previously in Alzheimer's disease. In this report, antibodies
      specifically recognizing the active form of calpain 2 were used to investigate
      calpain 2 activation in a broad range of neurodegenerative diseases, utilizing
      multiple-label confocal immunofluorescence imaging. With rare exceptions, the
      active form of calpain 2 was found in colocalization with hyperphosphorylated tau
      protein. Aggregates of mutated huntingtin, alpha-synuclein, or unidentified
      protein in motor neuron disease type of frontotemporal dementia were always
      negative. These findings indicate that calpain 2 activation is not a general
      response to protein aggregation. In tauopathies, more pathological inclusions
      were labeled for hyperphosphorylated tau than for activated calpain 2. The extent
      of colocalization varied in both a disease-specific and cell-type specific
      manner. The active form of calpain 2 was detected in 50-75% of tau
      neurofibrillary pathology in Alzheimer's disease, Alzheimer neurofibrillary
      changes and Down's syndrome, as well as in the accompanying Alzheimer-type tau
      pathology in diffuse Lewy bodies disease, progressive supranuclear palsy, and
      corticobasal degeneration. For glial cells, only 10-25% of tuft-shaped
      astrocytes, glial plaques, or coiled bodies contained activated calpain 2. The
      majority of Pick bodies were negative. The association of calpain 2 activation
      with hyperphosphorylated tau might be the result of an attempt by the calpain
      proteolytic system to degrade the tau protein aggregates. Alternatively, calpain
      2 could be directly involved in tau hyperphosphorylation by modulating protein
      kinase activities. Overall, these results provide evidence of the important role
      of the calpain proteolytic system in the pathogenesis of neurodegenerative
      diseases with tau neurofibrillary pathology.

PMID- 12070672
TI  - Dangers of the amyloid-beta vaccination.

PMID- 12070671
TI  - Expression of survivin, an inhibitor of apoptosis protein, in tumors of the
      nervous system.
AB  - Survivin is an inhibitor of apoptosis protein that blocks apoptosis by binding to
      caspases-3 and -7. It is highly expressed in less-differentiated embryonic cells
      and rapidly dividing tumors, but not in terminally differentiated adult tissues.
      Elevated survivin levels are found in malignant systemic tumors, and are
      associated with chemo-resistance, radiation resistance, and poor prognosis.
      However, expression of survivin in primary nervous system tumors has not been
      previously characterized. Immunohistochemistry using anti-human survivin antibody
      (SURV11-A) was performed on formalin-fixed, paraffin-embedded archival tissue
      from 112 primary central nervous system tumors. Survivin immunoreactivity was
      seen in most diffuse astrocytomas [WHO II (2/4), III (3/3), IV (9/10), giant-cell
      glioblastoma (1), and gliosarcoma (1)]. The intensity and degree of survivin
      expression showed trends with tumor grade, with glioblastomas having the highest
      positivity. Pilocytic astrocytomas (5) and pleomorphic xanthoastrocytoma (1) were
      positive to a lesser degree. In oligodendrogliomas (6) and mixed oligo
      astrocytomas [grade II (5), II-III (3), and III (7)], oligodendroglial elements
      appear to be negative compared to positive mini-gemistocytic oligodendrocytes.
      Ependymomas [grade II (6) and grade III (1)] were positive. Medulloblastomas (5)
      and retinoblastoma (1/4) showed focal positivity. All meningiomas [grade I (12),
      II (9), III (4), and grade I (3) and II (5) with frank brain invasion] were
      intensely positive. All schwannomas (11) and neurofibromas (6) were intensely
      positive. Thus, survivin is expressed in the majority of the primary nervous
      system tumors, particularly in glioblastomas, meningiomas, schwannomas and
      neurofibromas. Overexpression of survivin in meningiomas and benign peripheral
      nerve sheath tumors contrasts with previous reports relating it to rapid division
      and poor prognosis.

PMID- 12070673
TI  - Alternatives to the suspended Alzheimer's disease vaccine.

PMID- 12070674
TI  - A 7-day oral treatment of patients with active rheumatoid arthritis using the
      prostacyclin analog iloprost: cytokine modulation, safety, and clinical effects.
AB  - OBJECTIVE: The purpose of this study was to investigate the plasma levels of
      tumor necrosis factor (TNF)-alpha, its soluble p55 and p75 receptors, ex vivo
      lipopolysaccharide (LPS)-stimulated TNF-alpha production, and plasma levels of
      interleukin 6, interleukin 1, and interleukin 10 during a 7-day oral
      administration of iloprost in patients with active rheumatoid arthritis. METHODS:
      During oral 7-day administration of the prostacyclin analog iloprost, the plasma
      levels of TNF-alpha, soluble p55, and p75 TNF-alpha receptors, IL-1, IL-6, and IL
      10 and C-reactive protein (CRP) in serum were determined on days -1, 1, 3, 4, 6,
      and 8 and after a treatment-free follow-up on day 15. In addition, the ex vivo
      TNF-alpha production in whole blood under LPS-stimulated and -unstimulated
      conditions were measured. Fifteen patients with active rheumatoid arthritis and
      baseline TNF-alpha plasma levels of > or =2 pg/ml were included in independent
      groups receiving 50 microg, 100 microg, or 150 microg iloprost per day in
      addition to their conventional antirheumatic therapy. The respective dose was
      given once daily from days 1 to 3 and doubled from days 4 to 7. The tender and
      swollen joint count (28 joints) and the patients' assessments of pain severity
      and general feeling (10-cm visual analog scale) were performed on days -1, 4, and
      8 (end of treatment) and after a 7-day follow-up. RESULTS: The patients showed
      decreased TNF-alpha levels during iloprost administration. The decrease in the ex
      vivo LPS-stimulated TNF-alpha production and plasma levels of the p75 TNF
      receptor were found to be associated with a decrease in the number of tender
      joints. Additionally, IL-6 was downregulated. CONCLUSION: A 7-day oral
      administration of iloprost resulted in a change of in vivo and ex vivo cellular
      cytokine production, with reductions in TNF-alpha and p75 TNF receptor plasma
      levels. These changes were associated with clinical improvements in active
      rheumatoid arthritis.

PMID- 12070676
TI  - The effects of balneotherapy on fibromyalgia patients.
AB  - Fibromyalgia syndrome (FMS) is a very common rheumatological diagnosis. There are
      various treatment modalities. This study was planned to investigate the effects
      of balneotherapy in the treatment of FMS. A total of 42 primary fibromyalgia
      patients diagnosed according to American College of Rheumatology criteria were
      included in the study. Their ages ranged between 30 and 55 years. Patients were
      randomly assigned to two groups. None of them had had a cardiovascular disease
      before. Group 1 n=22) received 20-min bathing, once a day and five times per
      week. Patients participated in the study for 3 weeks (total of 15 sessions).
      Group 2 (n=20) was accepted as the control group. Patients were evaluated by the
      number of tender points, Visual Analogue Scale for pain, Beck's Depression Index
      for depression, and Fibromyalgia Impact Questionnaire for functional capacity.
      Measurements were assessed initially, after the therapy, and at the end of the
      6th month. In group 1, there were statistically significant differences in
      numbers of tender points, Visual Analogue scores, Beck's Depression Index, and
      Fibromyalgia Impact Questionnaire scores after the therapy program (P<0.001).
      Also, 6 months later in group 1, there was still an improvement in the number of
      tender points (P<0.001), Visual Analogue scores, and Fibromyalgia Impact
      Questionnaire (P<0.005). But there was not a statistical difference in Beck's
      Depression Index scores compared to the control group (P>0.05). Patients with FMS
      mostly complain about pain, anxiety, and the difficulty in daily living
      activities. This study shows that balneotherapy is effective and may be an
      alternative method in treating fibromyalgia patients.

PMID- 12070675
TI  - Expression of the anaphylatoxin receptor C5aR (CD88) by human articular
      chondrocytes.
AB  - Although the complement system is implicated in the inflammatory process in
      arthritic diseases, a direct interaction between chondrocytes and complement has
      not been demonstrated. In this study, we investigated expression of the C5a
      receptor (C5aR) on chondrocytes of cartilage from patients with rheumatoid
      arthritis (RA), osteoarthritis (OA), and bone fracture as normal controls by
      reverse transcriptase polymerase chain reaction (RT-PCR), flow cytometry, and
      immunohistochemistry. The RT-PCR detected mRNA for C5aR in most or all of the
      tested samples (73% in OA, 100% in RA, 89% in normal). The FACS analysis revealed
      different expression ratios between individuals varying from 0.7% to 77.1%;
      however, expression ratios of C5aR were significantly higher in RA than in
      controls (26.0% in RA, 9.0% in OA, 6.9% in normal). The expression of C5aR was
      upregulated significantly by addition of IL-1beta in RA and normal samples but
      not in OA. In addition, the C5aR-positive chondrocytes were confirmed by
      immunohistochemistry. In conclusion, expression of C5aR and the effect of IL
      1beta on the expression were different between RA and OA. The C5aR may contribute
      to chondrocyte metabolism and the pathogenesis of arthritis differently between
      in RA and OA.

PMID- 12070677
TI  - Folinic acid antagonizes methotrexate-induced differentiation of monocyte
      progenitors.
AB  - OBJECTIVE: The anti-inflammatory action of low-dose methoxetrate (MTX) in the
      treatment of rheumatoid arthritis (RA) appears to be partially impaired by folate
      supplementation. Here we investigated whether a folate excess impairs monocyte
      differentiation, a putative anti-inflammatory action of low-dose MTX. METHODS:
      Monocyte differentiation of U937 promonocytic cells was assessed by CD11b and
      CD14 immunostaining and fluorescent absorbent cell sorting (FACS) analysis. Cell
      proliferation and viability were determined by cell counts and trypan-blue
      staining, respectively. Nuclear apoptosis was assessed by 7-actinomycin staining.
      Cells were treated with 10(-10)-10(-6) M MTX in the presence or absence of
      folinic acid. Exposure to 1,25-OH-vitamine D(3) and TGF-beta served as a positive
      control of monocyte differentiation in U937 cells. RESULTS: Low-dose MTX-induced
      monocyte differentiation was marginal when compared with 1,25-OH-D(3) + TGF-beta
      treatment. Low-dose MTX inhibited cell proliferation, induced apoptosis, and
      reduced cell viability. All the antiproliferative, cytotoxic, and monocyte
      differentiating effects of MTX were completely reversed by folinic acid.
      CONCLUSIONS: Monocyte differentiation is part of the folate-dependent MTX
      actions.

PMID- 12070678
TI  - Prevalence of carpal tunnel syndrome in patients with fibromyalgia.
AB  - This study was planned to investigate the prevalence of carpal tunnel syndrome
      (CTS) in patients with fibromyalgia (FM) and the normal population. Paresthesia
      in the hands, sensory and motor deficits, and atrophy of the thenar muscles of 50
      patients with FM and 50 matched control subjects were evaluated. Tinel's and
      Phalen's signs and bilateral electrophysiological studies of the median nerves
      were performed. The differences between the groups in terms of paresthesia (13 FM
      patients, two control subjects, P<0.01) and sensory deficits (four FM patients, 0
      control subjects, P<0.05) were statistically significant. In the FM and the
      control groups, a total of five (10%) and two (4%) cases of CTS were documented
      electrophysiologically, respectively. However, the difference between the groups
      in CTS prevalence was not statistically significant ( P>0.05). In conclusion,
      paresthesias are a common symptom and associated condition of FM patients.
      Together with sensory deficits in the hands, they should remind the physician of
      the possibility of undiagnosed CTS.

PMID- 12070679
TI  - Soluble HLA in saliva of patients with autoimmune rheumatic diseases.
AB  - OBJECTIVES: The limited number of studies addressing the presence of soluble
      human leukocyte antigen (HLA) in body fluids such as tears, urine, sweat, and
      saliva are restricted to healthy subjects. In this study, we applied solid-phase
      enzyme-linked immunoassay to quantify soluble HLA class I (sHLA-I) and class II
      (sHLA-II) molecules in saliva and in selected serum samples obtained from
      patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and
      Sjogren's syndrome (SS). RESULTS: While saliva from normal subjects (n=35)
      contained levels of sHLA-I that were undetectable (n=7) or ranged from 9 ng/ml to
      70 ng/ml (30+/-3.7 ng/ml, n=28), sHLA-I among 38 patients with moderately active
      RA ( n=24) or SLE (n=14) were significantly elevated (222+/-81.4 ng/ml and 120+/
      27.3 ng/ml, respectively, P<0.0001). Intriguingly, sHLA-I levels were even higher
      in patients whose disease was regarded as active. Specifically, sHLA-I averaged
      683+/-189 ng/ml in patients with active RA (n=13) and 230+/-24.5 ng/ml in
      patients with active SLE (n=7). This was significantly higher than in patients
      with milder forms of these diseases (P<0.0001). All five subjects with SS had
      severe disease with high levels of sHLA-I (mean 486+/-86 ng/ml). The
      concentrations of saliva sHLA-II in the disease groups studied were comparable
      with levels found in normal controls. The sHLA-I in severe and mild states was
      investigated in purified serum and saliva from a patient with SS. While 44-kDa
      fragments of serum HLA-I were detectable in severe SS, they were undetectable in
      saliva HLA at any time; 35-37-kDa fragments of serum or saliva HLA-I were
      detected during both mild and severe disease. Interestingly, the 39-kDa fragment
      was detected in both body fluids during severe but not mild forms of SS.
      Similarly, the isoforms with the molecular masses 39 kDa and 44 kDa were mainly
      identified in the purified material obtained from serum of SLE patients.
      CONCLUSIONS: Collectively, our data suggest that the measurement of soluble HLA
      in body fluids can be of both diagnostic and prognostic value in the assessment
      of patients with autoimmune rheumatic disorders. The mechanism by which sHLA
      enters saliva is unclear, but they probably are not acquired from serum.

PMID- 12070680
TI  - Stress fractures in rheumatological practice: clinical significance and
      localizations.
AB  - The objective of this study was to analyze the clinical characteristics,
      associated disorders, and the most common sites of stress fractures in
      rheumatological patients. Over a 3-year period, 35 patients with 44 stress
      fractures were prospectively recruited from an outpatient rheumatological
      department (32 postmenopausal women and three men aged 47 to 86 years, mean 70+/
      10.6 years). Clinical diagnosis was established by compatible clinical and
      radiological data. In addition, previous skeletal fractures were recorded in all
      patients. Bone mass assessment was performed in 23 patients and spinal X-ray in
      21. The diagnosis of osteoporosis was defined by the presence of atraumatic
      vertebral fractures and/or densitometric criteria (lumbar or femoral bone mass <
      2.5 T score). The most frequent stress fractures were: pelvic ring (13 sacrum and
      eight pubic) and metatarsal (11 fractures), followed by tibia (seven fractures),
      calcaneus (three fractures), femur (one), and tarsal (one). Nine patients (26%)
      presented simultaneous stress fractures. Twenty-four patients (69%) suffered
      previous osteoporotic fractures, vertebral and Colles' fractures being the most
      frequent. Most of the evaluated patients (25 out of 30) had osteoporosis (83%).
      Six patients had associated disorders (glucocorticoids use in three patients,
      neurologic disorders in two, and rheumatoid arthritis in one). Except for the
      patient with a femur fracture which required internal fixation, no other clinical
      complications were observed after conservative treatment. In conclusion,
      fractures of the pelvic ring, especially sacrum, and metatarsal are the most
      frequent stress fractures in rheumatological practice. The association with
      osteoporosis and the history of prior low-trauma fractures are common in these
      patients.

PMID- 12070681
TI  - Poststreptococcal reactive arthritis in children: is it really a different entity
      from rheumatic fever?
AB  - Poststreptococcal reactive arthritis (PSRA) is an acute, nonsuppurative arthritis
      following documented streptococcal infections. Although most authors accepted it
      as a different entity, the differences from acute rheumatic fever (ARF) are not
      clear. To document and compare the clinical and laboratory characteristics of
      PSRA and ARF, 24 patients with PSRA and 20 with ARF were enrolled in the study.
      The latency period from upper respiratory tract infection was shorter in patients
      with PSRA ( P<0.01). However, 25% of the patients with ARF had also short (<10
      days) latency periods. Although symmetric and nonmigratory arthritis were more
      frequent in patients with PSRA, there was no significant difference for the
      distribution of mono-, oligo-, and polyarticular disease between PSRA and ARF
      patients. The frequency of small joint and hip involvement was also similar
      between the patient groups. Unresponsiveness of articular symptoms to salicylate
      therapy within 72 h was more frequent in patients with PSRA (P<0.001). However,
      in a substantial part of the patients with ARF (nine patients, 45%), joint
      symptoms also had no response during the first 72 h. Since there is a
      considerable overlap of symptoms, signs, and laboratory features of PSRA and ARF,
      a line between these two entities could not be easily drawn. We conclude that
      these two conditions are actually different presentations of the same disease.

PMID- 12070682
TI  - Circulating interleukin-6, soluble interleukin-2 receptors, tumor necrosis factor
      alpha, and interleukin-10 levels in juvenile chronic arthritis: correlations with
      soft tissue vascularity assessed by power Doppler sonography.
AB  - Nineteen patients with juvenile chronic arthritis (JCA), ten with systemic (s)
      JCA, and nine with polyarticular-onset (p)-JCA were examined for interleukin (IL)
      6, tumor necrosis factor (TNF)-alpha, IL-2R, and IL-10 levels. Power Doppler
      sonography (PDS) for the more affected knee was used in all of them to evaluate
      soft tissue vascularity. Serum levels of IL-6 were significantly higher in JCA
      patients than in controls (P<0.007). Patients with p-JCA showed higher levels of
      IL-6 than patients with s-JCA, and the difference was statistically
      nonsignificant. Serum IL-6 levels in all patients correlated significantly with
      the degree of vascularity detected by PDS (P<0.01). This correlation was more
      pronounced in p-JCA patients (P<0.01 in p-JCA vs P<0.05 in s-JCA). Serum levels
      of TNF-alpha were higher in patients with JCA than in controls (P<0.0001). Serum
      levels of TNF-alpha were significantly greater in patients with s-JCA than in p
      JCA (P=0.008). Soluble IL-2R levels were higher in patients with JCA than
      controls (P<0.0002). Serum levels of IL-2R correlated significantly with pannus
      thickness in p-JCA (P<0.01) and inversely with methoxetrate (MTX) duration in s
      JCA (P<0.05). Serum levels of IL-10 were significantly higher in JCA patients
      than in controls ( P<0.0008). Serum IL-10 levels in all patients correlated
      significantly inversely with hemoglobin levels (r=-0.50, P<0.05), total
      leukocytic count (TLC) (r=-0.58, P<0.01), and intra-articular steroid injection
      (r=+0.56, P<0.01). In s-JCA, IL-10 levels correlated significantly with MTX
      weekly dose ( P<0.05). In conclusion, a significant correlation of serum IL-6
      levels with the degree of knee joint vascularity was found, and this correlation
      was more pronounced in p-JCA, which may stress the role of IL-6 as an inducer of
      neoangiogenesis in JCA.

PMID- 12070683
TI  - Purification, characterization, and chemical modification of manganese peroxidase
      from Bjerkandera adusta UAMH 8258.
AB  - Ten strains of Bjerkandera adusta from the University of Alberta Microfungus
      Collection and Herbarium (UAMH) were compared for manganese peroxidase
      production. The enzyme from B. adusta UAMH 8258 was chosen for further study.
      After purification the enzyme showed a molecular weight of 43 kDa on 15% SDS
      PAGE, 36.6 kDa on matrix-assisted laser desorption ionization-time of flight mass
      spectrometry, and an isoelectric point of 3.55. The N-terminal amino acid
      sequence was determined to be VAXPDGVNTATNAAXXALFA, and the amino acid
      composition showed no tyrosine residues in the enzyme. Manganese peroxidase
      exhibited both Mn(II)-dependent (optimum pH 5) and Mn(II)-independent activity
      (optimum pH 3). The purified enzyme was chemically modified with cyanuric
      chloride-activated methoxypolyethylene glycol to enhance its surface
      hydrophobicity. The modified and native enzymes showed similar catalytic
      properties in the oxidation of Mn(II) and other substrates such as 2,6
      dimethoxylphenol, veratryl alcohol, guaiacol, and 2,2'-azino-bis(3
      ethylbenzthiazoline-6-sulfonate). However, the modified enzyme showed greater
      resistance to denaturation by hydrogen peroxide and stability to organic solvents
      such as acetonitrile, N,N-dimethylformamide, tetrahydrofuran, methanol, and
      ethanol. The PEG-modified enzyme also showed greater stability to higher
      temperatures and lower pH than the native enzyme. Thus, chemical modification of
      manganese peroxidase from B. adusta increases its potential usefulness for
      applied studies.

PMID- 12070684
TI  - Microbiological transformation of L-tyrosine to 3,4-dihydroxyphenyl L-alanine (L
      dopa) by a mutant strain of Aspergillus oryzae UV-7.
AB  - The present study deals with the microbiological transformation of L-tyrosine to
      3,4-dihydroxyphenyl L-alanine by a mutant strain of Aspergillus oryzae UV-7.
      Sixteen different mutant strains of Aspergillus oryzae (GCB-6) were isolated
      through UV-irradiation. These mutant strains were screened for the production of
      mold mycelia by submerged fermentation in 250-ml Erlenmeyer flasks. Of all the
      mutant strains examined, UV-7 gave maximum production of L-dopa (1.28 mg/ml). The
      reaction was carried out using mold mycelium as a source of enzyme tyrosinase in
      shake flasks. The maximum production of L-dopa was obtained when glucose (25
      mg/ml) was used as the carbon source and NH(4)Cl (3 mg/ml) was used as the
      nitrogen source. The optimum pH for mycelium development was 5.0; L-dopa
      production was maximum at pH 3.5 of the reaction mixture. The reaction by mold
      mycelium (75 mg/ml) was carried out under acidic conditions. Optimum temp, time,
      and L-tyrosine concentration were 55 degrees C, 60 min, and 3.0 mg/ml,
      respectively.

PMID- 12070685
TI  - Biosynthesis of the branched-chain amino acids in the cyanobacterium
      Synechocystis PCC6803: existence of compensatory pathways.
AB  - Complementation of an E. coli mutant auxotrophic for the branched-chain amino
      acids (BCAA)--valine, leucine, and isoleucine--by the ilvG gene ( slr2088) of the
      cyanobacterium Synechocystis PCC6803 indicates that this gene encodes an active
      alpha-acetohydroxy acid synthase. Differences of response of the recombinants to
      the addition of the essential amino acids suggested a lower specificity for the
      initial reaction of the valine/leucine chain than for the isoleucine one.
      Inactivation of ilvG in Synechocystis led to a leaky phenotype, suggesting a
      capacity to compensate the auxotrophies by other processes. This observation is
      discussed in view of the general difficulty of obtaining auxotrophs in
      cyanobacteria.

PMID- 12070686
TI  - Isolation and characterization of a chlorate-resistant mutant (Clo- R) of the
      symbiotic cyanobacterium Nostoc ANTH: heterocyst formation and N(2)-fixation in
      the presence of nitrate, and evidence for separate nitrate and nitrite transport
      systems.
AB  - Nostoc ANTH is a filamentous, heterocystous cyanobacterium capable of N(2)
      fixation in the absence of combined nitrogen. A chlorate-resistant mutant (Clo-
      R) of Nostoc ANTH was isolated that differentiates heterocysts and fixes N(2) in
      the presence of nitrate, but not in the presence of nitrite or ammonium. The
      mutant lacks nitrate uptake and thereby also lacks induction of nitrate reductase
      activity by nitrate. However, this mutant is able to transport and assimilate
      nitrite, indicating that there is a transport system for nitrite that is distinct
      from that for the nitrate. The lack of inhibitory effect of nitrate on N(2)
      fixation was owing to lack of nitrate uptake and not to lack of enzymes for its
      assimilation (nitrate reductase and glutamine synthetase) or the lack of an
      ammonium transport system for retention of ammonia. The mutant has potential for
      use as a biofertilizer supplementing chemical nitrate fertilizer in rice fields,
      without N(2)-fixation being adversely affected.

PMID- 12070687
TI  - In vitro adhesion to human cells by viable but nonculturable Enterococcus
      faecalis.
AB  - The ability of viable but nonculturable (VBNC) Enterococcus faecalis to adhere to
      Caco-2 and Girardi heart cultured cells and to urinary tract epithelial cells
      (ECs) was studied. Enterococci were harvested during the vegetative growth phase
      (early exponential and stationary), in the VBNC state, and after recovery of the
      ability to divide. VBNC bacteria maintained their adherence capability but the
      efficiency of attachment was reduced by about 50 to 70%, depending on the target
      cell employed. The decrease was transient, since enterococci that regained their
      culturability showed adherence values similar to those observed for actively
      growing cells. Analysis of the invasive properties of E. faecalis revealed that
      the VBNC state caused a decrease in the number of bacteria that entered the
      cultured HEK cells as a result of the reduction in the number of adhering
      bacteria. These results highlight the importance of studies of the VBNC
      phenomenon, with respect to both microbial survival in the environment and the
      impact on human health.

PMID- 12070688
TI  - Campylobacter fetus subspecies venerealis surface array protein from bovine
      isolates in Brazil.
AB  - The electrophoretic patterns of 31 Campylobacter fetus subspecies venerealis
      capsular Surface Array Protein (SAP) isolated from bovines in reproduction from
      different regions of Brazil were analyzed. The persistence of the bacteria in the
      reproductive tract of naturally infected bovines and the dynamic of SAP
      expression were also evaluated. Cervical mucous and prepucial aspirates from five
      animals naturally infected were cultured for isolation of Campylobacter fetus and
      the SAPs extracted from the bacteria isolated were analyzed by SDS-PAGE. Ten
      different patterns of SAP expression were demonstrated by the identification of
      proteins with molecular mass of 97, 100, 127, and 149 kDa, respectively. The most
      prevalent identified protein had a molecular mass of 100 kDa (41.9%). Taking into
      consideration the time during which the five animals were evaluated, it was
      possible to conclude that one of these animals persisted with the etiological
      agent up to 171 days. The five naturally infected bovines analyzed presented
      variation on their surface protein pattern during the period of this study. C.
      fetus subspecies venerealis persisted in the reproductive tract of naturally
      infected animals. In natural condition of infection C. fetus subspecies
      venerealis persisted in an intermittent condition and an alteration of the
      protein surface was shown.

PMID- 12070689
TI  - Two Copies of form I RuBisCO genes in Acidithiobacillus ferrooxidans ATCC 23270.
AB  - Acidithiobacillus ferrooxidans ATCC 23270 possesses two copies of form I ribulose
      bisphosphate carboxylase/oxygenase (RuBisCO). The nucleotide sequence identity
      between the two large and two small subunit peptides was 75% and 58%,
      respectively. It is proposed that the two copies resulted from lateral gene
      transfer.

PMID- 12070690
TI  - Exposure of Porphyromonas gingivalis to red light in the presence of the light
      activated antimicrobial agent toluidine blue decreases membrane fluidity.
AB  - Porphyromonas gingivalis, one of the etiological agents of periodontitis, can be
      killed by red light in the presence of toluidine blue. The purpose of this study
      was to determine whether this light-induced killing was accompanied by changes in
      the fluidity of the organism's cytoplasmic membrane. A suspension of the organism
      was exposed to red light in the presence of toluidine blue, and the membrane
      fluidity was monitored spectrofluorimetrically by using the membrane probe
      trimethylammonium diphenyl hexatriene. The fluidity of the organism's cytoplasmic
      membrane was found to decrease significantly during lethal photosensitization,
      and this was accompanied by membrane condensation and vacuolation of the cells.
      Although changes in membrane fluidity are often attributable to lipid
      peroxidation, malonaldehyde (a product of lipid peroxidation) was not detectable.
      The disruption of membrane functions associated with a decreased membrane
      fluidity may contribute to the bactericidal effect of light-activated toluidine
      blue.

PMID- 12070691
TI  - Cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer
      hydrolase from Acidovorax sp. strain SA1 and purification of the enzyme.
AB  - The gene of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase (i3HBOH)
      was cloned and sequenced from a poly(3-hydroxybutyrate) (PHB)-degrading
      bacterium, Acidovorax sp. strain SA1. The i3HBOH gene has 876 nucleotides
      corresponding to the deduced sequence of 292 amino acids. In this amino acid
      sequence, the general lipase box sequence (G-X(1)-S-X(2)-G) was found, whose
      serine residue was determined to the active sites serine by site-directed
      mutagenesis. An i3HBOH was purified to electrophoretical homogeneity from SA1.
      The molecular mass of the purified enzyme was estimated to be 32 kDa by SDS-PAGE.
      The N-terminal amino acid sequence of the purified enzyme corresponded to the
      deduced N-terminal amino acid sequence in the cloned i3HBOH gene. This is the
      first cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer
      hydrolase gene to date.

PMID- 12070692
TI  - Campylobacter coli pulsed field gel electrophoresis genotypic diversity among
      sows and piglets in a farrowing barn.
AB  - Genotypes of Campylobacter coli isolates from feces of three sows and rectal
      swabs of 17 piglets were examined by pulsed field gel electrophoresis (PFGE). All
      of the animals originated from a single farrowing barn of a farrow-to-finish
      swine operation. Five Campylobacter colonies were picked from a single agar plate
      for each sample after broth enrichment and growth on Campy-Cefex agar. Genotypes
      were examined by PFGE after genomic DNA digestion with SmaI and SacII restriction
      endonucleases. Twenty SmaI genotypes and 12 SacII genotypes were detected among
      99 Campylobacter coli isolates. There was no pattern of shared genotypes between
      sows and their respective piglets, nor between littermates. Results indicate that
      a high number of Campylobacter genotypes may coexist in related pigs from a
      single housing facility.

PMID- 12070693
TI  - Expression of the full-length and 3'-spliced cry1Ab gene in the 135-kDa crystal
      protein minus derivative of Bacillus thuringiensis subsp. kyushuensis.
AB  - Bacillus thuringiensis produces a 130-135-kDa insecticidal protein in the form of
      bipyramidal crystal which is toxic to lepidopteran larvae. Part of the C-terminal
      region of the native Cry1Ab was replaced by a heterologous sequence of Cry11Aa C
      terminus to get a 3'-spliced cry1Ab gene. The full-length cry1Ab and 3'-spliced
      cry1Ab, which were both cloned into the E. coli-B. thuringiensis shuttle
      expression vector pHZB1, were expressed in a 135-kDa crystal protein minus
      derivative of B. thuringiensis subsp. kyushuensis (4U1-Cry(-135)). The crystal
      shape of Cry1Ab proteins from both recombinants was regularly bipyramidal, while
      the crystal size of the intact Cry1Ab was approximately fivefold larger than the
      3'-spliced Cry1Ab. In addition, these two kinds of Cry1Ab proteins had similar
      toxicity against Argyrogramma agnata larvae.

PMID- 12070694
TI  - Phylogenetic analysis of Bacillus thuringiensis based on PCR amplified fragment
      polymorphisms of flagellin genes.
AB  - Phylogenetic analysis of 35 strains of Bacillus thuringiensis was performed based
      on PCR amplified fragment polymorphisms of flagellin genes (PCR-AFPF). From
      coefficient matrix, the genetic distance coefficient D among them ranged from
      0.14286 to 0.81818. Ten clusters were divided by the taxonomic threshold of 0.42
      from the UPGMA dendrogram, demonstrating that the genetic dissimilarities existed
      among 35 strains of B. thuringiensis corresponding to 35 different serovars. This
      method could provide a fast, convenient and accurate way to classify all
      subspecies of B. thuringiensis including strains that can not be classified using
      the H-antigen method.

PMID- 12070695
TI  - Thermophilic protease-producing Geobacillus from Buranga hot springs in Western
      Uganda.
AB  - Two proteolytic thermophilic aerobic bacterial strains, PA-9 and PA-5, were
      isolated from Buranga hot springs in western Uganda. The cells were rods,
      approximately 10-12 microm in length and 3 microm in width. Isolate PA-9 grew at
      between 38 degrees C and 68 degrees C (optimum, 62 degrees C), and PA-5 grew at
      between 37 degrees C and 72 degrees C (optimum, 60 degrees C). Both isolates grew
      optimally at pH 7.5-8.5. Their 16S rRNA gene sequences indicated that they belong
      to the newly described genus Geobacillus. Zymogram analysis of the crude enzyme
      extracts revealed the presence of two extracellular proteases for isolate PA-5,
      and at least eight for isolate PA-9. The optimum temperature and pH for casein
      degrading activity were 70 degrees C, pH 6.5 for isolate PA-9, but caseinolytic
      activity could also be observed at 2 degrees C. In the case of isolate PA-5,
      optimal activity was observed over a temperature and pH range of 50-70 degrees C
      and pH 5-10, respectively.

PMID- 12070710
TI  - The role of CD8(+) T cells in immune responses to colorectal cancer.
AB  - Cytotoxic T lymphocytes (CTL) are essential effectors of the cell-mediated immune
      response. The ability of CTL to specifically recognise and lyse malignant cells
      expressing the relevant surface antigens under optimal in vitro conditions
      justifies attempts to boost their number and activity through various forms of
      immunotherapy. Considering the high prevalence of colorectal cancer and poor
      survival rates for patients with advanced-stage disease, the development of new
      protocols based on CTL stimulation represents a genuine and promising treatment
      option. Significant advances in recombinant DNA technology and molecular biology
      have led to the identification of a number of tumour-associated antigens (TAA).
      These have served as vaccine constituents and/or stimuli for obtaining CTL used
      for adoptive immunotherapy after in vitro stimulation and expansion. The present
      review describes the properties and functions of CTL as effectors of the immune
      response against tumours, and summarises the known TAA recognised by CTL and the
      current status of CTL-related immunotherapeutic interventions in colorectal
      cancer patients.

PMID- 12070711
TI  - Interferon-alpha (Intron A) upregulates urokinase-type plasminogen activator
      receptor gene expression.
AB  - The regulation of urokinase plasminogen activator receptor (uPAR) gene expression
      by interferon-alpha (IFN-alpha, or Intron A) and interferon-gamma (IFN-gamma) was
      studied in a HCT116 colon cancer cell line. uPAR mRNA levels were increased in a
      dose- and time-dependent manner in cells stimulated with IFN-alpha or IFN-gamma.
      uPAR protein levels reflected IFN-alpha and IFN-gamma induction of uPAR mRNA
      production. Cycloheximide, a protein synthesis inhibitor, also induced uPAR mRNA
      accumulation either alone or in combination with IFN-alpha or IFN-gamma,
      suggesting that the effect on uPAR mRNA levels activated by IFN-alpha or IFN
      gamma does not require de novo protein synthesis. Both sodium butyrate and
      amiloride inhibited the uPAR mRNA levels induced by IFN-alpha or IFN-gamma. These
      results may provide useful information for the treatment of patients receiving
      IFN-alpha or IFN-gamma.

PMID- 12070712
TI  - Treatment with GM-CSF and IL-2 in patients with metastatic colorectal carcinoma
      induced high serum levels of neopterin and sIL-2R, an indicator of immune
      suppression.
AB  - Cytokines may enhance the effect of therapeutic monoclonal antibodies (mAb).
      Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL
      2) have been shown to increase ADCC levels. GM-CSF may augment the induction of
      an idiotypic network response (anti-tumour immunity). The clinical anti-tumour
      effect of a combination of mouse mAb17-1A-1A [anti-colorectal carcinoma (CRC)],
      and GM-CSF was, however, not enhanced by the addition of IL-2. In the present
      study, some immune functions considered to be involved in mAb-mediated tumour
      cell killing were analysed in patients receiving GM-CSF and GM-CSF/IL-2
      respectively together with the mAb17-1A-1A. Ten patients received mAb17-1A and GM
      CSF, and ten patients mAb17-1A with GM-CSF and IL-2. During a 10- day cytokine
      treatment period, a significantly higher increase in white blood cell counts was
      noted in the GM-CSF/IL-2 treatment group as compared to GM-CSF-treated patients.
      In the GM-CSF/IL-2 group, significantly higher serum concentrations of neopterin
      and soluble IL-2 receptor (sIL-2R) respectively were induced as compared to GM
      CSF-treated patients. However, the ADCC of peripheral blood mononuclear cells
      (PBMC) against a CRC cell line was significantly higher in the GM-CSF group than
      in the GM-CSF/IL-2 group. The frequencies of patients developing human anti-mouse
      antibodies (HAMA) and anti-idiotypic antibodies were the same in both groups,
      while serum concentrations were significantly lower in the GM-CSF/IL-2 group as
      compared to the GM-CSF group. GM-CSF/IL-2 therapy seems to induce an immune
      suppressive stage compared to GM-CSF alone affecting cytotoxic mononuclear cells
      and B cells, which might be mediated through the neopterin metabolic pathway or
      other inducible immune suppressive factors such as reactive oxygen and nitrogen
      intermediates.

PMID- 12070713
TI  - Induction of Tc2 cells with specificity for prostate-specific antigen from
      patients with hormone-refractory prostate cancer.
AB  - Prostate-specific antigen (PSA) is a potentially useful antigen for targeted T
      cell immunotherapy of prostate cancer (CaP). Our laboratory has identified a
      synthetic nonamer peptide (PSA 146-154) homologue of PSA, which binds to the
      prevalent human leukocyte antigen, HLA-A2, and elicits specific cytotoxic T
      lymphocyte (CTL) responses from normal individuals of the HLA-A2 phenotype. In
      the present study, we report on the induction of CTL from peripheral blood
      mononuclear cells (PBMC) of patients with hormone-refractory CaP, which exhibit
      the same specificity. T-cell lines were established from two patients by
      stimulation of PBMC with PSA 146-154 peptide in vitro. The T-cell lines exhibited
      specific cytolytic activity against T2 cells pulsed with PSA 146-154 peptide, but
      not a control HLA-A2 binding peptide (HIV-RT 476-484) via chromium release assay
      (CRA). The T-cell lines also showed PSA 146-154 peptide-specific IL-4 responses,
      but no detectable interferon-gamma (IFN-gamma) responses via enzyme-linked immuno
      spot assays. Magnetic immuno-selection studies of one of the T-cell lines
      demonstrated that both cytolytic and interleukin-4 (IL-4) responses were mediated
      by CD8(+), but not by CD4(+) T cells. This Tc2 line was further characterized for
      the ability to recognize endogenously processed PSA epitopes. The line
      specifically secreted IL-4 in response to HLA-A2(+) target cells transfected to
      express PSA and specifically lysed the PSA(+) target cells, but not control
      transfected cells. The results indicate that the PSA 146-154 peptide emulates a
      naturally processed and presented peptide epitope of PSA that is within the T
      cell repertoire of HLA-A2(+)patients with CaP.

PMID- 12070714
TI  - Prediction of an HLA-DR-binding peptide derived from Wilms' tumour 1 protein and
      demonstration of in vitro immunogenicity of WT1(124-138)-pulsed dendritic cells
      generated according to an optimised protocol.
AB  - The Wilms' tumour 1 (WT1) protein is over-expressed in several types of cancer
      including leukaemias and might therefore constitute a novel target for
      immunotherapy. Recently, human leucocyte antigen (HLA) class I-binding WT1
      peptides have been identified and shown to stimulate CD8(+) T cells in vitro. For
      maximal CD8 cell efficacy, CD4(+) helper T cells responding to major
      histocompatibility complex (MHC) class II-binding epitopes are required. Here, we
      report that scanning the WT1 protein sequence using an evidence-based predictive
      computer algorithm (SYFPEITHI) yielded a peptide WT1(124-138) predicted to bind
      the HLA-DRB1*0401 molecule with high affinity. Moreover, synthetic WT1(124-138)
      peptide-pulsed dendritic cells (DC), generated according to a protocol optimised
      in the present study, sensitised T cells in vitro to proliferate and secrete
      interferon-gamma (IFN-gamma) when rechallenged with specific peptide-pulsed DC,
      but not with peripheral blood mononuclear cells (PBMC). These results suggest
      that the WT1 protein may yield epitopes immunogenic to CD4 as well as CD8 T
      cells, and therefore constitute a novel potential target for specific
      immunotherapy.

PMID- 12070716
TI  - Is the presence of interleukin-2 receptor alpha in the serum of colorectal liver
      metastases patients derived from hepatic natural killer cells?

PMID- 12070715
TI  - Frequent detection of anti-recoverin cytotoxic T-lymphocyte precursors in
      peripheral blood of cancer patients by using an HLA-A24-recoverin tetramer.
AB  - Recoverin is a photoreceptor-specific calcium binding protein that is only
      expressed in the retina in normal tissues. Aberrant expression of recoverin,
      however, has been observed in several cancer tissues and may cause a very rare
      autoimmune disease, cancer-associated retinopathy (CAR). It has been suggested
      that CAR-positive cancer patients have a more favorable prognosis than CAR
      negative cancer patients. To estimate the status of recoverin-specific T cells in
      such cancer patients, we generated an HLA-A24-recoverin peptide tetramer. By use
      of the tetramer, we could directly assess the frequency of CTL precursors (CTLp)
      of 20 HLA-A24(+) cancer patients with ten colon, six stomach and four breast
      cancers, and seven healthy individuals. Four cancer patients showed a CTLp
      frequency higher than 0.9%. Seven cancer patients including the former four
      patients and two healthy individuals showed specific anti-recoverin cytotoxic
      responses in an HLA-A24-restricted manner after in vitro stimulation with the
      recoverin peptide. Moreover, five cancer patients analyzed in an independent
      experiment using different peripheral blood mononuclear cells (PBMC) samples
      showed similar CTLp and cytotoxic T lymphocyte (CTL) frequencies and cytotoxic
      responses, suggesting that the CTLp frequency analyzed by the tetramer and the
      cytotoxic response may have a good correlation. Thus, we hypothesize that anti
      recoverin CTLp may exist in some cancer patients, and that anti-recoverin CTL may
      be readily induced.

PMID- 12070718
TI  - Factors related to the magnitude of T2* MR signal changes during functional
      imaging.
AB  - Our aim was to determine whether age, sex, the degree of weakness,
      anticonvulsants, the histology of the underlying lesion(s), the presence of
      oedema or the distance of the lesion from the motor region have an impact on the
      blood oxygenation level-dependent (BOLD) signal strength and therefore on the
      validity of functional MRI (fMRI). We studied 98 patients with masses near the
      central region imaged for surgical planning at 1.5 tesla, employing a BOLD
      sequence during a motor task. We calculated percentage signal change in the
      primary motor cortex between rest and activation and carried out multiple linear
      regression to examine the impact of the above factors on signal strength. Using a
      stepwise analysis strategy, the distance of the lesion from the motor region had
      the strongest influence (r=0.653, P<0.001). The factor with largest uncorrelated
      additional impact on signal change was the presence of oedema. Both predictors
      together formed a highly significant multiple r=0.739 ( P<0.001). No other
      predictive factor was identified (all P>0.20). Disturbances of cerebral blood
      flow and metabolism induced by the tumour were presumed to be the causes of a
      decrease in signal in the adjacent cortex.

PMID- 12070719
TI  - Determination of hemisphere dominance for language: comparison of frontal and
      temporal fMRI activation with intracarotid amytal testing.
AB  - The reliability of frontal and temporal fMRI activations for the determination of
      hemisphere language dominance was evaluated in comparison with intracarotid
      amytal testing (IAT). Twenty-two patients were studied by IAT (bilateral in 13,
      unilateral in 9 patients) and fMRI using a paradigm requiring semantic decisions.
      Global and regional (frontal and temporoparietal) lateralisation indices (LI)
      were calculated from the number of activated (r>0.4) voxels in both hemispheres.
      Frontolateral activations associated with the language task were seen in all
      patients, temporoparietal activations in 20 of 22. Regional LI corresponded
      better with IAT results than global LI. Frontolateral LI were consistent with IAT
      in all patients with bilateral IAT (including three patients with right dominant
      and one patient with bilateral language representation) and were not conflicting
      in any of the patients with unilateral IAT. Temporoparietal LI were discordant
      with IAT in two patients with atypical language representation. In the
      determination of hemisphere dominance for language, regional analysis of fMRI
      activation is superior to global analysis. In cases with clear-cut fMRI
      lateralisation, i.e. consistent lateralised activation of frontal and
      temporoparietal language zones, IAT may be unnecessary. FMRI should be performed
      prior to IAT in all patients going to be operated in brain regions potentially
      involved in language.

PMID- 12070720
TI  - Diffusion and perfusion MRI for the localisation of epileptogenic foci in drug
      resistant epilepsy.
AB  - Drug-resistant epilepsy is an important clinical challenge, both diagnostically
      and therapeutically. More and more surgical options are being considered, but
      precise presurgical assessment is necessary. We prospectively studied eight
      patients with drug-resistant epilepsy, who underwent clinical examination, single
      photon emission computed tomography (SPECT) and interictal MRI, including
      diffusion- and perfusion-weighted echoplanar sequences. Lesions suspected on
      SPECT of being epileptogenic showed mild hypoperfusion, while the diffusion
      weighted MRI (DWI) revealed increased apparent diffusion coefficients relative to
      the other side. However, these abnormalities were not visible on the
      corresponding maps. We showed that DWI and perfusion-weighted MRI could be used
      confirm the characteristics and site of an epileptogenic area in patients with
      drug-resistant epilepsy.

PMID- 12070721
TI  - Diffusion-weighted magnetic resonance imaging of dural sinus thrombosis.
AB  - Magnetic resonance imaging (MRI) is useful to diagnose dural sinus thrombosis.
      However, the representative appearance of dural sinus thrombosis on diffusion
      weighted MRI has not been established. This study was aimed at determining
      whether cytotoxic or vasogenic edema is more predominant in the affected cerebral
      parenchyma and assessing the time courses and prognosis of dural sinus thrombosis
      lesion. The studies on sixteen patients with dural sinus thrombosis who underwent
      diffusion-weighted MRI were retrospectively reviewed. The diagnosis was confirmed
      by digital subtraction angiography in 11 patients and magnetic resonance
      angiography in five patients. Diffusion-weighted images with echo-planar imaging
      were obtained using two or three b values, with the highest b value of up to
      1,000 s/mm(2). A region of interest was placed on an area of abnormal signal
      intensity to calculate apparent diffusion coefficients (ADCs). Nine of the 16
      patients had lesions with an increased ADC, whereas, three of these nine patients
      also had lesions with a decreased ADC. Among 11 patients who underwent initial
      MRI within 7 days of their last episode, eight had lesions with an increased ADC,
      of whom three had lesions mixed with both decreased and increased ADC areas.
      Follow-up studies of these three patients revealed the development of hemorrhagic
      infarction in two and subcortical hemorrhage in one. Vasogenic edema develops
      more predominantly and earlier in dural sinus thrombosis, though cytotoxic edema
      was also associated with the pathological changes in the early phase. Decrease of
      ADC value is presumed to reflect severe pathological conditions and indicate
      possible future development of infarction or hemorrhage.

PMID- 12070722
TI  - Concentric structure of thalamic lesions in acute necrotizing encephalopathy.
AB  - Acute necrotizing encephalopathy of childhood (ANE) is characterized by multiple,
      symmetrical brain lesions affecting the bilateral thalami, putamina and cerebral
      white matter, which often show a concentric structure on CT and MRI. To reveal
      the pathological substrate of this finding, comparison was made between CT and
      necropsy findings of three fatal cases of ANE. Cranial CT demonstrated a
      concentric structure of the thalamocerebral lesions in one patient who died 3.5
      days after the onset of encephalopathy, but not in the other two patients who
      died within 30 h. Neuropathological examination of postmortem brains revealed
      laminar changes of vascular and parenchymal pathology in all the cases. Excessive
      permeability of blood vessels and resultant vasogenic edema became more prominent
      with increasing depth from the cerebral surface. The deep portion of the lesions
      showed severe perivascular hemorrhage, accounting for the central high density on
      the CT images of one patient.

PMID- 12070723
TI  - Myelopathy and sciatica induced by an extradural S1 root haemangioblastoma.
AB  - Haemangioblastomas are vascular tumours which mainly involve the central nervous
      system and retina, often in the setting of von Hippel-Lindau disease.
      Haemangioblastomas occurring outside the central nervous system are uncommon.
      Wherever it is, recognising this tumour prior to surgery is desirable, as
      preoperative embolisation may be considered. We report the clinical, imaging and
      pathological features of a sporadic sacral root haemangioblastoma in a 58-year
      old man with chronic sciatica and myelopathy. The diagnosis was questioned
      preoperatively because an enlarged sacral foramen, seen to be filled by a highly
      vascular, enhancing mass and dilated vessels. Myelopathy was attributed to the
      presumed high venous pressure resulting from increased flow in veins draining the
      vascular tumour. Microneurosurgical excision was performed after endovascular
      embolisation and led to persistent clinical improvement.

PMID- 12070724
TI  - Diffusion-weighted MRI of maple syrup urine disease encephalopathy.
AB  - We report the case of a newborn child with maple syrup urine disease (MSUD),
      diagnosed at 10 days of life. Diffusion-weighted echoplanar MRI showed marked
      hyperintensity of the cerebellar white matter, the brainstem, the cerebral
      peduncles, the thalami, the dorsal limb of the internal capsule and the centrum
      semiovale, while conventional dual-echo sequence evidenced only a weak diffuse T2
      hyperintensity in the cerebellar white matter and in the dorsal brainstem. The
      apparent diffusion coefficient (ADC) of these regions was markedly (>80%)
      decreased. Therefore, in agreement with current hypotheses on MSUD pathogenesis,
      MSUD oedema proves to be a cytotoxic oedema. Diffusion-weighted MRI may be a
      valuable tool, more sensitive than conventional spin-echo techniques, to assess
      the extent and progression of cytotoxicity in MSUD, as well as the effectiveness
      of the therapeutic interventions.

PMID- 12070725
TI  - Combined stent implantation and embolization with liquid 2-polyhydroxyethyl
      methacrylate for treatment of experimental canine wide-necked aneurysms.
AB  - The purpose of the study was the evaluation of 2-polyhydroxyethyl methacrylate (2
      P-HEMA) for endovascular liquid embolization of experimental side-wall aneurysms
      following stent protection in a canine model. The swelling behaviour and
      polymerization characteristics of 2-P-HEMA in different solutions were
      investigated in vitro. Different methods for applications were tested in a latex
      aneurysm model under pulsatile flow conditions. Twenty broad-based carotid side
      wall aneurysms were microsurgically produced in five dogs. Four weeks after
      surgery self-expandable nitinol stents were placed, covering the orifice of the
      aneurysms. 2-P-HEMA was injected via a microcatheter, which was positioned
      through the meshwork of the stent. Control angiography was performed immediately
      after treatment and after 1, 6 and 9 months. In-vivo stent placement succeeded in
      all but one case. Two aneurysms occluded spontaneously after stent placement.
      Combined embolization of 17 aneurysms using a stent and 2-P-HEMA was performed.
      Eleven aneurysms could be primarily completely occluded (65%). A small remaining
      neck was evident in six aneurysms. Efflux of 2-P-HEMA during the process of
      embolization was observed in seven aneurysms, due to an excess volume of 2-P
      HEMA. The excessive 2-P-HEMA led to significant vessel stenosis in two cases. Two
      carotid arteries (three treated aneurysms) occluded after 1 month, due to
      insufficient anticoagulation management. Histological examination of embolized
      aneurysms revealed no foreign-body or inflammatory reaction. A smooth neo-intimal
      layer covered the stented vessel segment. Liquid embolization of side-wall
      aneurysms with 2-P-HEMA is technically feasible. Embolotherapy of aneurysms with
      liquid agents still has the risk that embolic material will exit even when it is
      stent-protected. To avoid this problem, stents with smaller strut diameter and/or
      additional balloon-protection are required. The inert 2-P-HEMA seems to be a
      promising agent for combining techniques of aneurysm treatment.

PMID- 12070726
TI  - Intensive care management of patients with severe intracerebral haemorrhage after
      endovascular treatment of brain arteriovenous malformations.
AB  - We studied the impact of emergency neurosurgery and intensive care on the outcome
      for patients with severe intracerebral haemorrhage after endovascular treatment
      of brain arteriovenous malformations (AVMs). We reviewed the case notes of 18
      patients with severe haemorrhage after embolisation of a brain AVM between 1986
      and 2001. During this period the treatment changed: before 1993, these patients
      were not surgically treated, and they died, while after 1994, all patients
      underwent emergency surgery. We established a standardised protocol for emergency
      treatment and intensive care in May 1998, and emergency surgery was performed as
      soon as possible after the onset of symptoms of haemorrhage. Postoperative
      intensive care was according to a standardised regime. During these 15 years, 24
      out of 605 patients undergoing 1066 interventions had a haemorrhage during or
      after the procedure, of which 18 were severe (3% of patients, 1.7% of
      interventions). All patients had a severe clinical deficit (mean Glasgow coma
      scale 4.2); eight had uni- or bilateral mydriasis. From 1989 to April 1998 four
      (31%) of 13 patients died, one (7.5%) remained in a vegetative state and eight
      (61.5%) made a good recovery. All five patients treated between 1998 and 2001 had
      a favourable outcome. The mean time from onset of the symptoms of haemorrhage to
      reaching the operation room was 129 min between 1989 and 1998 and 24 min between
      1998 and 2001. Standardised emergency treatment and intensive care with early
      resuscitation, minimal radiological exploration before rapid surgery improved the
      outcome. A short time between the onset of the symptoms of haemorrhage and
      evacuation of the haematoma may be the most important factor for a favourable
      outcome.

PMID- 12070727
TI  - Patient and occupational dose in neurointerventional procedures.
AB  - Neurointerventional procedures can involve very high doses of radiation to the
      patient. Our purpose was to quantify the exposure of patients and workers during
      such procedures, and to use the data for optimisation. We monitored the coiling
      of 27 aneurysms, and embolisation of four arteriovenous malformations. We
      measured entrance doses at the skull of the patient using thermoluminescent
      dosemeters. An observer logged the dose-area product (DAP), fluoroscopy time and
      characteristics of the digital angiographic and fluoroscopic projections. We also
      measured entrance doses to the workers at the glabella, neck, arms, hands and
      legs. The highest patient entrance dose was 2.3 Gy, the average maximum entrance
      dose 0.9+/-0.5 Gy. The effective dose to the patient was estimated as 14.0+/-8.1
      mSv. Other average values were: DAP 228+/-131 Gy cm(2), fluoroscopy time 34.8+/
      12.6 min, number of angiographic series 19.3+/-9.4 and number of frames 267+/
      143. The highest operator entrance dose was observed on the left leg (235+/-174
      microGy). The effective dose to the operator, wearing a 0.35 mm lead equivalent
      apron, was 6.7+/-4.6 microSv. Thus, even the highest patient entrance dose was in
      the lower part of the range in which nonstochastic effects might arise.
      Nevertheless, we are trying to reduce patient exposure by optimising machine
      settings and clinical protocols, and by informing the operator when the total DAP
      reaches a defined threshold. The contribution of neurointerventional procedures
      to occupational dose was very small.

PMID- 12070741
TI  - The vestibulo-ocular reflex in three dimensions.
AB  - The purpose of this paper is to review the kinematics and dynamics of the
      vestibulo-ocular reflex (VOR) in three dimensions. We give a brief, didactic
      tutorial on vectors and matrices and their importance as representational schemes
      for describing the kinematics and dynamics of the angular and linear
      accelerations that activate the vestibular system. We show how the vectors
      associated with angular and linear head accelerations are transformed by the
      peripheral and central vestibular systems to drive the oculomotor system to
      produce eye movements in three-dimensional space. We also review critical
      questions and controversies related to the compensatory and orientation behavior
      of the VOR. One such question is how the central vestibular system distinguishes
      tilts of the head, which generate interaural linear acceleration from
      translations along the interaural axis. Another question is how the velocity
      position integrator is implemented centrally. The review has been placed in the
      context of a model that explains the behavior of the VOR in three dimensions.
      Model processes have been related to peripheral and central neural behavior in
      order to gain insight into the nature of the three-dimensional organization and
      the controversial questions that are addressed.

PMID- 12070742
TI  - Grip and load force coupling during discrete vertical arm movements with a
      grasped object in cerebellar atrophy.
AB  - Control of isometric grip forces during manipulation of objects is an essential
      feature of all skilled manual performances. Recent studies suggested that the
      anticipation of movement-induced loads may be a cerebellar function. We analysed
      grip force adjustments to fluctuations of inertial loads during discrete vertical
      movements with a grasped object in five patients with cerebellar atrophy and five
      healthy control subjects. Normally grip force is precisely adapted to the load
      fluctuations, in particular to the maximum load force, which occurs early in
      upward and late in downward movements. Both groups produced similar accelerations
      of the grasped object and consequently similar maximum loads. However, cerebellar
      patients established increased static grip forces during stationary holding of
      the object and increased force ratios between grip and load force at the time of
      maximum acceleration. These findings are congruent with earlier studies analysing
      grip and load force coupling in patients with cerebellar lesions. In contrast to
      earlier studies, we found no significant differences in the timing of grip force
      onset and grip force maximum relative to the onset of movement and maximum
      acceleration, respectively, between normal controls and four of five cerebellar
      patients. However, a regression analysis between grip and load forces during the
      load increase and decrease phases of the movement suggested deficits in the close
      temporospatial coupling between the two forces in all cerebellar patients. Our
      findings give further support to the notion that the cerebellum plays a crucial
      role in the forward control of grip force magnitude and timing during voluntary
      object manipulation. Compared to earlier studies, the increase in grip forces may
      be interpreted as a general control strategy to compensate for motor deficits,
      whereas impairments of temporal grip force regulation may occur at different
      degrees of dysfunction during the progression of cerebellar atrophy.

PMID- 12070744
TI  - Dynamic and predictive links between touch and vision.
AB  - We investigated crossmodal links between vision and touch for moving objects. In
      experiment 1, observers discriminated visual targets presented randomly at one of
      five locations on their forearm. Tactile pulses simulating motion along the
      forearm preceded visual targets. At short tactile-visual ISIs, discriminations
      were more rapid when the final tactile pulse and visual target were at the same
      location. At longer ISIs, discriminations were more rapid when the visual target
      was offset in the motion direction and were slower for offsets opposite to the
      motion direction. In experiment 2, speeded tactile discriminations at one of
      three random locations on the forearm were preceded by a visually simulated
      approaching object. Discriminations were more rapid when the object approached
      the location of the tactile stimulation and discrimination performance was
      dependent on the approaching object's time to contact. These results demonstrate
      dynamic links in the spatial mapping between vision and touch.

PMID- 12070743
TI  - Afferent mechanisms for the reflex response to imposed ankle movement in chronic
      spinal cord injury.
AB  - We have reported earlier that externally imposed ankle movements trigger ankle
      and hip flexion reflexes in individuals with spinal cord injury (SCI). In order
      to examine the afferent mechanisms underlying these movement-triggered reflexes,
      controlled ankle movements were imposed in 17 SCI subjects. In 13 of these
      subjects, reflex torques were recorded at the hip, knee and ankle in response to
      5 ankle movement ranges, and 4 movement speeds. Subjects were tested using both
      ankle plantarflexion and dorsiflexion movements. The principal outcome measure,
      peak hip flexion torque of the induced reflexes, was used for comparing the
      effects of movement range and speed on the reflex response. We found that
      movement-triggered reflexes were sensitive to the angular range of ankle
      deflection, but insensitive to the velocity of the movement. Movement amplitudes
      sufficient to trigger hip and ankle flexion were routinely associated with
      increases in ankle passive force, suggesting that force-sensitive receptors
      participated in the reflex response. However, increases in angular range also
      corresponded to increases in muscle length, making it difficult to distinguish
      whether the response was triggered by a load-sensitive receptor (e.g., Golgi
      tendon organ or muscle free nerve ending) or a position-sensitive receptor
      responsive to absolute ankle angle (e.g., muscle spindle secondary afferent). The
      absence of velocity dependence of the reflex suggested that spindle Ia afferents
      were not major contributors. These results suggest movement-triggered reflexes
      originate in muscle receptors that are sensitive to either absolute muscle
      length, to muscle force or to both. Although receptors that are sensitive to
      absolute muscle length cannot be excluded with certainty, the finding that reflex
      responses require that ankle movements elicit an increase in passive force argues
      for a prominent role of nonspindle mechanoreceptors, such as group III/IV muscle
      afferents. These afferents are activated preferentially as muscles are stretched
      to near maximum length, and they appear to have potent reflex effects in spinal
      cord injury.

PMID- 12070745
TI  - Displaced retinal ganglion cells project to the accessory optic system in the
      chameleon ( Chamaeleo calyptratus).
AB  - Retinal ganglion cells were successfully labelled in the chameleon by retrograde
      axonal transport of dextran amines that were applied to the nucleus of the basal
      optic root (nBOR) in an in vitro preparation. Labelled ganglion cells were
      restricted to the contralateral eye. Many cells were completely stained including
      their dendritic trees. With few exceptions, all cells had displaced somata that
      were located at the inner margin of the inner nuclear layer. The labelled
      ganglion cells had two to six primary dendrites that branched frequently and
      formed large unistratified dendritic trees within sublamina 1 of the inner
      plexiform layer. There was extensive overlap of the dendritic trees of
      neighbouring cells leading to an estimated coverage factor of 2-4. The dendritic
      field areas varied in size according to the retinal position of the cells and
      were highest in the central retina around the fovea with a maximum of 0.14 mm(2)
      and reached a second maximum at the retinal margin with values of 0.08-0.1 mm(2).
      The smallest dendritic areas (0.04-0.06 mm(2)) were measured midway between the
      fovea and retinal margin. The size of the soma area was not correlated to the
      dendritic field size and increased from 100 to 150 microm(2) near the fovea to
      150-300 microm(2) at the retinal margin. There was no evidence for a retinotopic
      organisation of ganglion cell fibres within the nBOR. All cells were of uniform
      morphology that was identical to the type of nBOR-projecting displaced ganglion
      cell (DGC) described previously for the bird retina. Similar to birds, the
      labelled DGCs were the only source of retinal projection to the nBOR. A small
      fraction of cells had orthotopic somata located in the ganglion cell layer but
      were otherwise identical to the labelled DGCs. The similarity of chameleon nBOR
      projecting ganglion cells to those described in avian retinas mirrors the close
      phylogenetic relationship of birds and lizards.

PMID- 12070746
TI  - Atypical on-, off- and neutral cells in the rostral ventromedial medulla
      oblongata in rat.
AB  - It is generally assumed that the response pattern of on-, off- and neutral cells
      in the rostral ventromedial medulla (RVM) to noxious stimulation is independent
      of stimulation site. But recent studies have shown that a remarkable number of
      RVM neurons do not have whole-body receptive fields. These so-called atypical
      neurons were extracellularly recorded in lightly anaesthetized rats. The
      receptive fields to noxious thermal and mechanical stimulation applied to the
      tail, the extremities and the craniofacial region were determined in 57 RVM
      neurons. In 24 atypical off-cells, 12 on-cells and 21 neutral cells, the response
      pattern evoked by noxious pinch to the nose, forehead and ear most frequently
      differed from the responses to noxious tail heat. The modulatory effects of
      intravenously administered morphine were examined in 21 cells. In contrast to the
      general assumption that morphine activates off-cells, inhibits on-cells and has
      no effect on neutral cells, in atypical RVM neurons 5 of 6 off-cells, 2 of 6 on
      cells and 5 out 9 neutral cells showed a different response pattern to systemical
      administration of morphine. The results show that a RVM cell classification that
      is exclusively based on the behaviour to noxious tail heat can neither
      sufficiently predict the response pattern to different noxious stimuli,
      especially in the craniofacial region, nor reliably predict the modulatory effect
      of morphine in RVM neurons. The fact that the neutral cells responded in an off
      or on manner to noxious stimulation different from noxious tail heat and that
      morphine modulated activity in many neutral cells suggests that these cells are
      probably subtypes of on- and off-cells.

PMID- 12070747
TI  - Effort-induced mirror movements. A study of transcallosal inhibition in humans.
AB  - During sustained, fatiguing maximal voluntary contraction of muscles of one hand,
      muscles of the other hand gradually become activated also. Such effort-induced
      mirror movements indicate a decreased ability of the central nervous system (CNS)
      to selectively control individual muscles. We studied whether altered
      transcallosal inhibition (TCI) contributed to this phenomenon. TCI was determined
      in ten healthy subjects by measuring the ipsilateral silent period (iSP) and the
      contralateral silent period (cSP) during a sustained contraction of the abductor
      digiti minimi, induced by focal unihemispheric ipsilateral transcranial magnetic
      stimulation. Mirror movements occurred in all subjects in response to the effort.
      There was a bilateral increase in cSPs and a parallel increase in the iSP in the
      contralateral working muscle. In contrast, the iSP in the mirroring muscle
      remained unchanged, explained by a balance of increased crossed pyramidal
      inhibition (cSP) and decreased transcallosal inhibition. In finely tuned
      unimanual movements, mirroring activity of the contralateral hand is suppressed
      by TCI originating in the working hemisphere. During sustained, effortful
      contractions, the outflow of the contralateral hemisphere is increased due to
      reduced TCI. Effort-induced mirror contractions are thus the result of
      disinhibition of contralateral crossed projections rather than disinhibition of
      ipsilateral uncrossed pathways.

PMID- 12070748
TI  - Effect of mild hypothermia on energy state recovery following transient forebrain
      ischemia in the gerbil.
AB  - A transient (lasting for 15 min) bilateral carotid artery occlusion model was
      created by using male Mongolian gerbils ( n=20, weight 50-60 g). The animals were
      divided into a group with mild hypothermia (34 degrees C, n=10) and a
      normothermic group (37 degrees C, n=10). High-energy phosphate metabolism (ATP,
      PCr, Pi) and intracellular pH were sequentially measured using (31)P-MRS during
      ischemia and after reperfusion for 1 week. The same animals were also subjected
      to a histopathological evaluation. During ischemia, there were no statistically
      significant differences between the two groups in the quantities of the
      metabolites. However, after reperfusion the rate of metabolic recovery by the
      mildly hypothermic (MH) group was significantly higher (by 10-20%) than the
      normothermic (NT) group. The intracellular pH decreased about 0.4 in both groups
      after ischemia; and after reperfusion the intracellular pH of the MH group
      returned to baseline levels faster than in the NT group. One week after ischemia,
      energy metabolism gradually decreased about 10-20% in both groups. In the
      histopathological evaluation, pyramidal cell damage in the hippocampus was 33% on
      average in the MH group and 79% in the NT group. The neuronal damage to the
      cerebral cortex was 26% in the MH group and 61% in the NT group. Astrocyte
      reactivity in the hippocampus and cerebral cortex was 2.9% and 1.1% in the MH
      group and 9.7% and 5.2% in the NT group. The results of this experiment indicate
      that the protective effect of mild hypothermia is due to the high recovery rate
      of ATP and PCr and the prevention of a secondary decline in high phosphate
      energy.

PMID- 12070749
TI  - Parietal inputs to dorsal versus ventral premotor areas in the macaque monkey:
      evidence for largely segregated visuomotor pathways.
AB  - The lateral premotor cortex plays a crucial role in visually guided limb
      movements. Visual information may reach this cortical region from the parietal
      cortex, the highest stage in the dorsal visual stream. Anatomical studies
      indicate that the parietal projections to the dorsal (PMd) and ventral (PMv)
      premotor areas arise from separate parietal regions, supporting the notion of
      parallel visuomotor pathways. We tested the degree of segregation of these
      pathways by injecting retrograde tracers into PMd and PMv in the same monkeys,
      under physiological control. Eleven injections were made in four animals, and the
      analysis of retrograde labelling revealed that parietal cells projecting to PMd
      and those projecting to PMv are largely segregated. The strongest projections to
      PMd arise from the superior parietal lobule, including the medial intraparietal
      area (MIP), PEc and PGm, and the parieto-occipital area. These areas were devoid
      of labelling following injections into PMv, which receives its major projections
      from the anterior intraparietal area (AIP), area PEip, the anterior portion of
      the inferior parietal gyrus (area 7b), and the somatosensory areas. In addition
      to their strong projections to PMv, areas 7b and PEip send minor projections to
      PMd as well. Additional projections to PMd arise from the ventral intraparietal
      area and the inferior parietal lobule. The present findings are direct anatomical
      evidence for largely segregated visuomotor pathways linking parietal cortex with
      PMd and PMv.

PMID- 12070750
TI  - Predictive responses of periarcuate pursuit neurons to visual target motion.
AB  - The smooth pursuit eye movement system uses retinal information about the image
      slip-velocity of the target in order to match the eye-velocity-in-space (i.e.,
      gaze-velocity) to the actual target velocity. To maintain the target image on the
      fovea during smooth gaze tracking, and to compensate for the long delays involved
      in processing visual motion information and/or eye velocity commands, the pursuit
      system must use prediction. We have shown recently that both retinal image-slip
      velocity and gaze-velocity signals are coded in the discharge of single pursuit
      related neurons in the simian periarcuate cortex. To understand how periarcuate
      pursuit neurons are involved in predictive smooth pursuit, we examined the
      discharge characteristics of these neurons in trained Japanese macaques. When a
      stationary target abruptly moved sinusoidally along the preferred direction at
      0.5 Hz, the response delays of pursuit cells seen at the onset of target motion
      were compensated in succeeding cycles. The monkeys were also required to continue
      smooth pursuit of a sinusoidally moving target while it was blanked for about
      half of a cycle at 0.5 Hz. This blanking was applied before cell activity
      normally increased and before the target changed direction. Normalized mean gain
      of the cells' responses (re control value without blanking) decreased to 0.81(+/
      0.67 SD), whereas normalized mean gain of the eye movement (eye gain) decreased
      to 0.65 (+/-0.16 SD). A majority (75%) of pursuit neurons discharged
      appropriately up to 500 ms after target blanking even though eye velocity
      decreased sharply, suggesting a dissociation of the activity of those pursuit
      neurons and eye velocity. To examine whether pursuit cell responses contain a
      predictive component that anticipates visual input, the monkeys were required to
      fixate a stationary target while a second test laser spot was moved sinusoidally.
      A majority (68%) of pursuit cells tested responded to the second target motion.
      When the second spot moved abruptly along the preferred direction, the response
      delays clearly seen at the onset of sinusoidal target motion were compensated in
      succeeding cycles. Blanking (400-600 ms) was also applied during sinusoidal
      motion at 1 Hz before the test spot changed its direction and before pursuit
      neurons normally increased their activity. Preferred directions were similar to
      those calculated for target motion (normalized mean gain=0.72). Similar responses
      were also evoked even if the second spot was flashed as it moved. Since the
      monkeys fixated the stationary spot well, such flashed stimuli should not induce
      significant retinal slip. These results taken together suggest that the
      prediction-related activity of periarcuate pursuit neurons contains extracted
      visual components that reflect direction and speed of the reconstructed target
      image, signals sufficient for estimating target motion. We suggest that many
      periarcuate pursuit neurons convey this information to generate appropriate
      smooth pursuit eye movements.

PMID- 12070751
TI  - Effects of methylphenidate on saccadic responses in patients with ADHD.
AB  - This study examined the effects of methylphenidate on different measures of
      saccade control, using a repeated measurement design, and the experimental and
      statistical control of practice effects. Twenty-seven boys with ADHD (mean age
      12.6 years, range 10-15 years) were randomly assigned to two testing order
      conditions (first on-, second off-medication versus first off-, second on
      medication) and accomplished the pro-saccadic overlap and the anti-saccadic 200
      ms gap tasks (200 trials each). Methylphenidate was found to reduce pro- and anti
      saccadic reaction times, error correction times, and the proportion of direction
      errors during the anti-saccade task. Furthermore, the drug augmented the
      proportions of express saccades and error corrections. Overlain practice effects
      were found for most of these measures. Our results suggest a weakening of the
      fixation, and a strengthening of the "voluntary" system of saccade control by
      methylphenidate.

PMID- 12070752
TI  - A comparison of postactivation depression of synaptic actions evoked by different
      afferents and at different locations in the feline spinal cord.
AB  - Postactivation depression of synaptic actions of group I and II muscle afferents
      and low threshold cutaneous afferents was compared with depression of actions of
      group Ia afferents on alpha-motoneurones in cats deeply anaesthetised with
      pentobarbital and alpha-chloralose. The depression was analysed on field
      potentials (population EPSPs). The degree of depression was evaluated by
      analysing changes in the monosynaptic components of the field potentials, in
      areas within 0.4- to 0.6-ms-long time windows from their onset. When intervals
      between successive stimuli used to evoke field potentials were reduced from 10 s
      to 0.4 s, the potentials evoked by Ia afferents in motor nuclei were depressed as
      described previously. Field potentials evoked by group II afferents and cutaneous
      afferents in the dorsal horn were similarly depressed. In contrast, monosynaptic
      components of field potentials evoked in the intermediate zone, by group I or II
      afferents, were only marginally affected. Postactivation depression of synaptic
      actions of group I afferents in the intermediate zone was not enhanced when test
      stimuli were applied 30-40 ms after a train of four conditioning stimuli. These
      observations indicate that the degree of postactivation depression may differ
      depending on the type of afferent. In addition, if postactivation depression
      depends on intrinsic properties of afferent terminals, differences in the degree
      of depression of postsynaptic potentials evoked by the same group of afferents at
      different locations may indicate that properties of terminals contacting
      different neurones may differ.

PMID- 12070753
TI  - Coding of disparity information in extrastriate cortex of the cat.
AB  - We have used information theory to analyse the responses of neurons in area 21a
      of the cat to disparity stimuli. Visual stimuli consisted of drifting sinusoidal
      gratings presented simultaneously to each eye. The relative spatial phase of the
      gratings varied between stimulus periods in a pseudo-random sequence of 45
      degrees increments that covered the full 360 degrees. The mean information
      content of the responses of all neurons across all phases was 0.72 bits (+/-0.10,
      SE, n=29). The information conveyed by each neuron was well correlated with the
      extent to which the interocular phase difference modulated the response of the
      cell. However, information content was not simply related to firing rate, as
      there was usually significant information content in the neuronal responses to
      phase differences that elicited the minimum firing rate. In general, burst
      responses (impulse intervals <4 ms) did not convey more information than that
      conveyed by the total response. The contribution to the cumulative information of
      the response in successive 100-ms segments decreased over the course of the 1-s
      stimulus. The ratio of information transmitted at 200 ms to that transmitted over
      the full second had a median of 0.30 while the ratio of 500 ms to 1 s was 0.68.

PMID- 12070754
TI  - DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer.
AB  - DM235 (sunifiram), a new compound structurally related to piracetam, prevented
      the amnesia induced by scopolamine (1.5 mg kg(-1) i.p.), after intraperitoneal
      (0.001-0.1 mg kg(-1)) or oral (0.01-0.1 mg kg(-1)) administration, as shown by a
      passive avoidance test in mice. The antiamnesic effect of DM235 was comparable to
      that of well-known nootropic drugs such as piracetam (30-100 mg kg(-1) i.p.),
      aniracetam (100 mg kg(-1) p.o.) or rolipram (30 mg kg(-1) p.o.). DM235 also
      prevented mecamylamine (20 mg kg(-1) i.p.)-, baclofen (2 mg kg(-1) i.p.)- and
      clonidine (0.125 mg kg(-1) i.p.)-induced amnesia in the same test. In the Morris
      water maze test with rats, scopolamine (0.8 mg kg(-1) i.p.) inhibited the
      reduction of escape latency in both acquisition and retention/retraining tests.
      DM235 (0.1 mg kg(-1) i.p.), 20 min before each daily acquisition training,
      prevented the scopolamine-induced memory impairment. DM235 (1 mg kg(-1) i.p.)
      also reduced the duration of pentobarbitone-induced hypnosis in mice without
      modifying the induction time of hypnosis. At the highest effective doses, the
      investigated compound neither impaired motor coordination (rota-rod test), nor
      modified spontaneous motility and inspection activity (Animex and hole board
      tests). These results indicate that DM235, a compound structurally related to
      piracetam, is a novel nootropic endowed with the capability to prevent cognitive
      deficits at very low doses. Indeed, its potency is about 1,000 times higher than
      that of the most active piracetam-like compounds.

PMID- 12070755
TI  - The neurotensin receptor antagonist SR 142948A blocks the efflux of dopamine
      evoked in nucleus accumbens by neurotensin ejection into the ventral tegmental
      area.
AB  - The neuropeptide neurotensin (NT) exerts a wide range of central and peripheral
      effects. In particular, ejection of NT (10(-7) M, 65 nl) into the ventral
      tegmental area (VTA) in anaesthetised rats pre-treated with pargyline increases
      the dopamine (DA) efflux within the nucleus accumbens (NAcc) as measured by
      differential pulse amperometry (DPA) combined with carbon fibre electrodes.
      However, this effect is not blocked by systemic pre-treatment with the potent and
      selective non-peptide NT receptor antagonists SR 48692 and SR 142948A, at any
      dose studied. The present study was designed to determine the ability of these NT
      receptor antagonists to block the increase in DA efflux evoked within the NAcc
      when they are locally applied with the peptide into the VTA. The competitive N
      methyl- D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid
      (AP-5), applied into the VTA 1 min before NMDA, blocked the effect of NMDA on DA
      efflux concentration and volume dependently, thus demonstrating the suitability
      of our experimental procedure for characterizing both an agonist and an
      antagonist specific for receptors present on mesencephalic dopaminergic neurons
      and involved in the regulation of DA efflux within the NAcc. Intra-VTA
      application of SR 142948A blocked the NT-evoked increase in DA efflux within the
      NAcc dose dependently whereas SR 48692, at the concentration used, was inactive.
      These results suggest that NT regulates mesencephalic dopaminergic activity
      through NT receptors sensitive to SR 142948A, but possibly not to SR 48692.

PMID- 12070756
TI  - Effects of prodelphinidins isolated from Ribes nigrum on chondrocyte metabolism
      and COX activity.
AB  - Articular diseases, such as osteoarthritis, is the clinical expression of the
      loss of cartilage function. COX inhibitors are widely used in the treatment of
      such pathologies for their beneficial effects on inflammation but often produce a
      negative activity on cartilage synthesis. In this study, we determined the effect
      of different prodelphinidins, the major compounds isolated from Ribes nigrum
      leaves, on the proteoglycans (PGs), type II collagen (coll. II) and prostaglandin
      E(2) (PGE(2)) production by differentiated human chondrocytes cultivated in long
      term (12 days) and in clusters as well as their inhibition potential on COX-1 and
      COX-2 in vitro. Gallocatechin trimer (GC-GC-GC) showed the higher stimulation of
      PGs and coll. II production (1 microg ml(-1)) and the synthesis of PGE(2) was
      significantly reduced by gallocatechin dimer (GC-GC), gallocatechin
      epigallocatechin (GC-EGC) and GC-GC-GC at 10 and 100 microg ml(-1). The
      inhibition of PGE(2) synthesis was confirmed by the in vitro test on purified COX
      enzymes, showing the selectivity of prodelphinidins on COX-2. However, the
      prodelphinidins had no effects on COX activity in the whole blood assay. Our
      studies suggest that the prodelphinidins fractions from R. nigrum may be useful
      as an additive agent in the prevention of osteoarthritis.

PMID- 12070757
TI  - Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)amide analogues. 1.
      In vitro studies.
AB  - Phe(4) in the nociceptin (NC) sequence has been identified as the most critical
      residue for receptor interaction. In the present study, we investigated the
      pharmacological activity of a series of NC(1-13)NH(2) analogues, in which the
      hydrogen atom in the para position of Phe(4) was substituted with F, NO(2), CN,
      Cl, Br, I, CH(3), OH or NH(2). In receptor binding studies, performed using CHO
      cells expressing the recombinant human NC receptor (CHO(hOP4)) and in rat
      cerebral cortex membranes, [(pF)Phe(4)]NC(1-13)NH(2), [(pNO(2))Phe(4)]NC(1
      13)NH(2), and [(pCN)Phe(4)]NC(1-13)NH(2) displayed higher affinity than NC(1
      13)NH(2). The affinity of [(pCl)Phe(4)]NC(1-13)NH(2) was essentially identical to
      that of NC(1-13)NH(2), while the remaining compounds displayed reduced affinity.
      In a series of functional assays (stimulation of GTPgammaS binding in
      CHO(hOP4)cells and rat cerebral cortex membranes and inhibition of cAMP
      accumulation in CHO(hOP4) cells), the para substituted analogues behaved as full
      agonists (with the exception of [(pOH)Phe(4)]NC(1-13)NH(2) which acted as a
      partial agonist in the GTPgammaS binding assays) with the following rank order
      potency:[(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2) were either
      inactive or displayed micromolar potencies in cAMP accumulation experiments
      performed on cells expressing classical opioid receptors. All compounds were full
      agonists in isolated tissues from various species (guinea pig ileum, mouse colon
      and mouse/rat vas deferens) with the exception of [(pOH)Phe(4)]NC(1-13)NH(2)
      which displayed partial agonist/weak antagonist activities. The rank order of
      potency was similar to that found in the other assays. The effects of all
      analogues were not modified by naloxone. The selective OP(4) receptor antagonist
      [Nphe(1)]NC(1-13)NH(2), tested in all preparations against one or both of the
      highly potent derivatives [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1
      13)NH(2), showed pA(2) values similar to those found against NC, the pA(2) in the
      GTPgammaS binding/rat cerebral cortex assay being much higher (ca. 7.5) than in
      the other functional assays (ca. 6). This study further supports the notion that
      Phe(4) of NC is the critical residue for receptor occupation and activation.
      Moreover, as part of this study, we have identified two novel, highly potent and
      selective agonists for the OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and
      [(pNO(2))Phe(4)]NC(1-13)NH(2).

PMID- 12070758
TI  - Pharmacological characterisation of [(pX)Phe4]nociceptin(1-13)NH2 analogues. 2.
      In vivo studies.
AB  - As part of a structure-activity study focused on the Phe(4) residue of nociceptin
      (NC) (1-13)NH(2), we identified two highly potent and selective agonists for the
      OP(4) receptor, [(pF)Phe(4)]NC(1-13)NH(2) and [(pNO(2))Phe(4)]NC(1-13)NH(2),
      whose in vitro pharmacological profiles have been described in the companion
      paper. In the present study, we investigated the actions of [(pF)Phe(4)]NC(1
      13)NH(2) and compared it with those of NC(1-13)NH(2) in a battery of vivo assays.
      In the locomotor activity test in mice, 1 nmol NC(1-13)NH(2) given
      intracerebroventricularly (i.c.v.) caused a significant decrease (about 70%
      inhibition) in activity for the first 15 min following injection;
      [(pF)Phe(4)]NC(1-13)NH(2), at the same dose, exerted a similar inhibitory effect
      that continued until the end of the observation period (30 min). This effect was
      prevented by the selective OP(4) receptor antagonist [Nphe(1)]NC(1-13)NH(2) (10
      nmol, i.c.v.). In the tail-withdrawal assay in mice, [(pF)Phe(4)]NC(1-13)NH(2)
      mimicked the effects of NC(1-13)NH(2) producing pronociceptive and antimorphine
      effects following i.c.v. administration. In both experimental paradigms, the
      actions of [(pF)Phe(4)]NC(1-13)NH(2) were longer lasting (>60 min) compared to
      those of NC(1-13)NH(2) (ca. 30 min). In unanaesthetised normotensive mice, bolus
      intravenous (i.v.) injection of 100 nmol/kg of [(pF)Phe(4)]NC(1-13)NH(2)
      decreased mean blood pressure and heart rate; these effects were longer lasting
      than those elicited by the same dose of NC(1-13)NH(2). I.c.v. administration of
      [(pF)Phe(4)]NC(1-13)NH(2) dose-dependently stimulated feeding in rats, and was
      about tenfold more potent than NC(1-13)NH(2).Collectively, the present data
      demonstrate that, in a variety of in vivo assays, NC(1-13)NH(2) and
      [(pF)Phe(4)]NC(1-13)NH(2) mimicked the actions of NC. [(pF)Phe(4)]NC(1-13)NH(2)
      was more potent and its in vivo effects were longer lasting than those of NC(1
      13)NH(2) and NC.

PMID- 12070760
TI  - Failure to detect in vivo inverse agonism of the 5-HT(1B) receptor antagonist SB
      224289 in 5-HT-depleted guinea-pigs.
AB  - The possibility that 5-HT(1B) receptors display constitutive activity in vivo,
      i.e. have a basal agonist-independent activity, was examined in guinea-pigs
      depleted of endogenous brain 5-HT by pre-treatment with reserpine. Under these
      conditions (5 mg/kg s.c. reserpine 24 h before the experiment), hypothalamic 5-HT
      concentration was reduced by more than 97%. In reserpine-treated animals, 5-HT
      synthesis [measured as the accumulation of 5-hydroxytryptophan (5-HTP) after
      inhibition of the aromatic amino acid decarboxylase with m-hydroxybenzylhydrazine
      dihydrochloride (NSD 1015, 100 mg/kg s.c.)] was similar to that in non-treated
      guinea-pigs. The formation of 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by
      reserpine treatment. The 5-HT(1B/1D) receptor agonist 3-( N-methylpyrrolidin-2- R
      ylmethyl)-5-(3-nitropyrid-2-ylamino)-1 H-indole (CP-135,807) decreased 5-HT
      synthesis and 5-HIAA formation to the same extent in reserpine-treated and naive
      animals showing that the terminal 5-HT(1B) autoreceptors were functionally active
      during reserpine treatment. The 5-HT(1B) inverse agonist 1'-methyl-5-([2'-methyl
      4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl)-4-yl]carbonyl)-2,3,6,7
      tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] hydrochloride (SB-224289, 4
      mg/kg s.c.), which in naive guinea-pigs significantly enhanced 5-HIAA formation
      and tended to enhance 5-HT synthesis, had no effect in the reserpine-treated
      animals. Likewise, SB-224289 did not change the rectal temperature in reserpine
      treated guinea-pigs although the agonist CP-135,807 had a significant hypothermic
      effect in these animals. It is concluded that no constitutive activity of 5
      HT(1B) autoreceptors (5-HIAA formation) or 5-HT(1B) heteroreceptors (rectal
      temperature) could be detected under the in vivo experimental conditions used.

PMID- 12070759
TI  - Inhibition of transport function and desipramine binding at the human
      noradrenaline transporter by N-ethylmaleimide and protection by substrate
      analogs.
AB  - N-ethylmaleimide (NEM) inhibits [(3)H]desipramine binding and [(3)H]noradrenaline
      uptake at the rat noradrenaline transporter (rNET) by covalently modifying
      cysteine residues. We report here that NEM also inhibits [(3)H]desipramine
      binding and [(3)H]noradrenaline uptake at the cloned human noradrenaline
      transporter (hNET) stably expressed in C6 glial cells. The IC(50) for NEM
      inhibition of [(3)H]noradrenaline uptake was 43.6+/-5.5 microM. We tested several
      compounds for their abilities to inhibit [(3)H]noradrenaline uptake via the hNET
      and for their abilities to protect against NEM inactivation of [(3)H]desipramine
      binding. We found that the substrate analogs bupropion, 3-bromomethcathinone, and
      4-bromomethcathinone all inhibit uptake at the hNET with IC(50) values of 1370+/
      140, 158+/-20, and 453+/-30 nM, respectively. These compounds as well as
      methamphetamine, methcathinone, and desipramine also protected the hNET from NEM
      inactivation of [(3)H]desipramine binding. The ability of substrate analogs and
      desipramine to protect the [(3)H]desipramine binding site is consistent with the
      hypothesis that the desipramine binding site and the substrate binding site are
      mutually exclusive. It also supports the use of structure-activity relationships
      derived from substrate analogs in the rational design of hNET uptake inhibitors.
      The hNET contains 10 cysteine residues whereas the rNET contains 12 cysteine
      residues. Since the hNET and the rNET are both inhibited by NEM, and because the
      NEM inhibition is protectable by desipramine and substrate analogs, we conclude
      that the two additional cysteine residues (C28 and C447) present in the rNET are
      not likely to be involved in desipramine binding or uptake function.

PMID- 12070761
TI  - Signalling components involved in the coupling of alpha 1-adrenoceptors to
      phospholipase D in neonatal rat cardiac myocytes.
AB  - Activation of phospholipase D (PLD) is assumed to be one major pathway by which
      alpha(1)-adrenoceptors (alpha(1)ARs) induce hypertrophic responses in cardiac
      myocytes. Heterotrimeric G proteins, protein kinase C (PKC) isoforms, protein
      tyrosine kinases, monomeric GTPases of the ADP-ribosylation factor (ARF) and Rho
      families, and as important cofactor phosphatidylinositol 4,5-bisphosphate
      (PIP(2)) seem to participate in the G protein-coupled receptor dependent
      regulation of PLD. We therefore studied the role of these components in the
      coupling of alpha(1)ARs to PLD in neonatal rat cardiac myocytes (NRCM).
      Stimulation of alpha(1)ARs, most likely of the alpha(1A) subtype, by
      noradrenaline increased PLD activity three- to fourfold concomitant with the
      stimulation of phospholipase C (PLC). In contrast, the partial agonist
      phenylephrine stimulated PLC, but failed to increase PLD activity. The PLC and
      PLD responses were pertussis toxin insensitive and treatment of the cells with
      the G(q)-activating toxin of Pasteurella multocida stimulated both phospholipases
      about fourfold. Over-expression of the G(q)-and G(i)-type-specific regulator of G
      protein signalling RGS4 blunted alpha(1)AR-induced PLC and PLD stimulation. Ro 31
      8220, known to inhibit Ca(2+)-dependent and -independent PKC isoforms, strongly
      inhibited PLD activity, whereas Go 6976, known to inhibit preferentially Ca(2+)
      dependent PKC isozymes, was without effect. The ARF signalling inhibitor
      brefeldin A, protein tyrosine kinase inhibitors and the Rho-inactivating toxin B
      of Clostridium difficile blunted alpha(1)AR-induced PLD stimulation and largely
      reduced the cellular PIP(2) content. In membranes of toxin B-treated NCRM, PLD
      activity was similarly reduced, but was fully restored by addition of exogenous
      PIP(2). We conclude, that alpha(1A)ARs stimulate PLD activity via a G(q/11)
      PLCbeta-novel PKC isoform-dependent pathway in NRCM. ARF and Rho GTPases as well
      as protein tyrosine kinases contribute to PLD stimulation in NRCM, most likely by
      regulating the supply of PIP(2).

PMID- 12070762
TI  - Peripherally applied candesartan inhibits central responses to angiotensin II in
      conscious rats.
AB  - In the brain, angiotensin II (Ang II) induces various effects such as blood
      pressure increase, the release of arginine vasopressin (AVP) and drinking
      behaviour. In the present study, we investigated the ability of the angiotensin
      II type-I (AT(1)) receptor antagonist, candesartan, administered peripherally, to
      block the central effects of Ang II. Experiments were performed in conscious rats
      instrumented with an intracerebroventricular (i.c.v.) cannula or a guide cannula
      into the paraventricular nucleus (PVN) and arterial and femoral catheters.
      Candesartan was administered intravenously (i.v.) at doses of 0.01, 0.1, 1 or 10
      mg/kg. Controls received vehicle (0.05 N Na(2)CO(3)). The drinking response (
      n=10-11 per group), the pressor response ( n=7-8) and the release of AVP into the
      circulation ( n=10-11) following i.c.v. Ang II (100 ng) were measured 0.5, 2, 4
      and 24 h following i.v. drug application. Candesartan inhibited the central
      responses to i.c.v. injected Ang II dose- and time-dependently. At the highest
      dose (10 mg/kg), the drinking and pressor responses and the release of AVP in
      response to i.c.v. Ang II were completely blocked at 4 h and still markedly
      inhibited 24 h after the antagonist application (by 85%, 48% and 86%,
      respectively). The lowest dose of the antagonist was without effect. In a further
      experiment, the release of AVP induced by microinjection of Ang II (100 ng) into
      the PVN was determined before and 4 h after administration of vehicle or
      candesartan (1 mg/kg, i.v.). Candesartan completely blocked the AVP release into
      the circulation induced by Ang II microinjection into the PVN. Our results
      demonstrate that candesartan administered peripherally effectively inhibits
      responses mediated by AT(1) receptors localised in periventricular brain regions
      as well as inside the blood-brain-barrier.

PMID- 12070763
TI  - Trehalose degradation and glucose efflux precede cell ejection during germination
      of heat-resistant ascospores of Talaromyces macrosporus.
AB  - Talaromyces macrosporus forms ascospores that survive pasteurization treatments.
      Ascospores were dense (1.3 g ml(-1)), relatively dry [0.6 g H(2)O (g dry weight)(
      1)] and packed with trehalose (9-17% fresh weight). Trehalose was degraded to
      glucose monomers between 30 and 100 min after heat activation of the spores. The
      maximal activity of trehalase was calculated as 400-520 nmol glucose formed min(
      1) (mg protein)(-1) as judged by measurements of the trehalose content of spores
      during germination. During early germination, glucose was released from the cell
      (10% of the cell weight or more). The intracellular concentration of glucose only
      peaked briefly. After 160-200 min, the protoplast encompassed by the inner cell
      wall was ejected through the outer cell wall in a very quick process.
      Subsequently, respiration of spores increased strongly. The data suggested that
      trehalose is primarily present for the protection of cell components as glucose
      is released from the cell. Then, an impenetrable outer cell wall is shed before
      metabolic activity increases.

PMID- 12070764
TI  - Isolation of an anaerobic intestinal bacterium capable of cleaving the C-ring of
      the isoflavonoid daidzein.
AB  - Colonic bacteria were screened for bacteria involved in the conversion of
      phytoestrogens. A gram-positive anaerobic bacterium, strain HGH 136, capable of
      conversion of the isoflavonoid daidzein, was isolated and identified as a
      Clostridium sp. The bacterium cleaved the C-ring of daidzein to produce O
      demethylangolensin ( O-Dma). This compound was identified by comparison of the
      HPLC retention time and UV spectrum of the metabolite with chemically synthesized
      O-Dma. The identity of the metabolite was confirmed by liquid chromatography-mass
      spectrometry and NMR using synthetic O-Dma as a standard. The bacterium incubated
      with synthetic dihydrodaidzein also produced O-Dma. After 3 days of incubation,
      28% of added daidzein and 12% of added dihydrodaidzein were converted to O-Dma.
      This is the first study in which an anaerobic bacterium involved in the ring
      cleavage of daidzein to produce O-Dma has been identified.

PMID- 12070766
TI  - Phylogenetic and metabolic diversity of bacteria degrading aromatic compounds
      under denitrifying conditions, and description of Thauera phenylacetica sp. nov.,
      Thauera aminoaromaticasp. nov., and Azoarcus buckelii sp. nov.
AB  - Six strains of denitrifying bacteria isolated from various oxic and anoxic
      habitats on different monocyclic aromatic substrates were characterized by
      sequencing 16S rRNA genes, determining physiological and morphological traits,
      and DNA-DNA hybridization. According to these criteria, strains S100, SP and
      LG356 were identified as members of Thauera aromatica. Strains B5-1 and B5-2 were
      tentatively affiliated to the species Azoarcus tolulyticus. Strains B4P and S2
      were only distantly related to each other and to other described Thauera species.
      These two strains are proposed as the type strains of two new species, Thauera
      phenylacetica sp. nov. and Thauera aminoaromaticasp. nov., respectively. By 16S
      rRNA gene analysis, strain U120 was highly related to the type strains of
      Azoarcus evansii and Azoarcus anaerobius, whereas corresponding DNA-DNA
      reassociation values indicated only a low degree of genomic relatedness. Based
      upon a low DNA similarity value and the presence of distinguishing physiological
      properties, strain U120 is proposed as the type strain of a new species, Azoarcus
      buckelii sp. nov. Almost all of the new isolates were obtained with different
      substrates. The highly varied substrate spectra of the isolates indicates that an
      even higher diversity of denitrifying bacteria degrading aromatic compounds would
      be discovered in the different habitats by using a larger spectrum of aromatic
      substrates for enrichment and isolation.

PMID- 12070765
TI  - TfdD(II), one of the two chloromuconate cycloisomerases of Ralstonia eutropha
      JMP134 (pJP4), cannot efficiently convert 2-chloro- cis, cis-muconate to trans
      dienelactone to allow growth on 3-chlorobenzoate.
AB  - Ralstonia eutropha JMP134 (pJP4) harbors two functional gene clusters for the
      degradation of chlorocatechols, i.e. tfdCDEF (in short: tfd (I)) and tfdD (II) C
      (II) E (II) F (II) (in short: tfd (II)), which are both present on the catabolic
      plasmid pJP4. In this study, we compared the function of both gene clusters for
      degradation of chlorocatechols by constructing isolated and hybrid tfd (I)- tfd
      (II) clusters on plasmids in R. eutropha, by activity assays of Tfd enzymes, and
      by HPLC/MS of individual enzymatic catalytic steps in chlorocatechol conversion.
      R. eutropha containing the tfd (II) cluster alone or hybrid tfd-clusters with
      tfdD (II) as sole gene for chloromuconate cycloisomerase were impaired in growth
      on 3-chlorobenzoate, in contrast to R. eutrophaharboring the complete tfd (I)
      cluster. Enzyme activities for TfdD(II) and for TfdE(II) were very low in R.
      eutropha when induced with 3-chlorobenzoate. By contrast, a relatively high
      enzyme activity was found for TfdF(II). Spectral conversion assays with extracts
      from R. eutropha strains expressing tfdD (II) all showed accumulation of a
      compound with a similar UV spectrum as 2-chloro- cis,cis-muconate from 3
      chlorocatechol. HPLC analysis of in vitro assays in which each individual step in
      3-chlorocatechol conversion was reproduced by sequentially adding cell extracts
      of an Escherichia coli expressing one Tfd enzyme only demonstrated that TfdD(II)
      was unable to cause conversion of 2-chloro- cis,cis-muconate. No accumulation of
      intermediates was observed with 4-chlorocatechol. From these results, we conclude
      that at least TfdD(II) is a bottleneck in conversion of 3-chlorocatechol and,
      therefore, in efficient metabolism of 3-chlorobenzoate. This study showed the
      subtle functional and expression differences between similar enzymes of the tfd
      encoded pathway and demonstrated that extreme care has to be taken when inferring
      functionality from sequence data alone.

PMID- 12070767
TI  - Involvement of the Sinorhizobium meliloti leuA gene in activation of nodulation
      genes by NodD1 and luteolin.
AB  - The role of leucine biosynthesis by Sinorhizobium meliloti in the establishment
      of nitrogen-fixing symbiosis with alfalfa ( Medicago sativa) was investigated.
      The leuA gene from S. meliloti, encoding alpha-isopropylmalate synthase, which
      catalyses the first specific step in the leucine biosynthetic pathway, was
      characterized. S. melilotiLeuA(-) mutants were Leu auxotrophs and lacked alpha
      isopropylmalate synthase activity. In addition, leuA auxotrophs were unable to
      nodulate alfalfa. Alfalfa roots did not seem to secrete enough leucine to support
      growth of leucine auxotrophs in the rhizosphere. Thus, this growth limitation
      probably imposes the inability to initiate symbiosis. However, in addition to the
      leucine auxotrophy, leuA strains were impaired in activation of nodulation genes
      by the transcriptional activator NodD1 in response to the plant flavone luteolin.
      By contrast, nod gene activation by NodD3, which does not involve plant-derived
      inducers, was unaffected. Our results suggest that a leucine-related metabolic
      intermediate may be involved in activation of nodulation genes by NodD1 and
      luteolin. This kind of control could be of relevance as a way to link bacterial
      physiological status to the response to plant signals and initiation of
      symbiosis.

PMID- 12070768
TI  - Characterization of Porphyrobacter sanguineus sp. nov., an aerobic
      bacteriochlorophyll-containing bacterium capable of degrading biphenyl and
      dibenzofuran.
AB  - Three strains of " Agrobacterium sanguineum", an aerobic marine bacterial species
      described previously, were re-characterized from phylogenetic and taxonomic
      viewpoints. 16S rDNA sequence comparisons showed that the " A. sanguineum"
      strains belong to the alpha-4 subgroup of alpha-Proteobacteria, with members of
      the genera Erythromicrobium and Porphyrobacter as their closest relatives. DNA
      DNA hybridization studies indicated that the " A. sanguineum" strains were
      distinguishable from any previously known species of these genera.
      Bacteriochlorophyll a, monosaccharide-type glycosphingolipids, 2-OH fatty acids
      of C14:0, C15:0, C16:0, and C16:1, and ubiquinone-10 were detected in the " A.
      sanguineum" strains. The G+C of the DNA was 63.8-64.0 mol%. Two of the " A.
      sanguineum" strains, IAM 12620 (=ATCC 25659) and ATCC 25661, were able to grow
      with biphenyl and dibenzofuran as sole carbon source in the presence of 0.05%
      yeast extract. The medium in these cultures turned yellowish-orange at the
      exponential phase of growth due to the release of soluble chromogenic
      metabolites. The remaining " A. sanguineum" strain, ATCC 25660, and all test
      strains of Erythromicrobium and Porphyrobacter neither grew nor produced yellow
      orange pigment with biphenyl or dibenzofuran. In PCR experiments, bphA1 gene,
      coding for the large subunit protein of biphenyl dioxygenase, was detected in "
      A. sanguineum" IAM 12620 and ATCC 25661. Based on these results, we propose
      classifying " A. sanguineum" IAM 12620 and ATCC 25661 as a new species of the
      genus Porphyrobacter with the name Porphyrobacter sanguineus sp. nov.

PMID- 12070769
TI  - Cysteine-mediated electron transfer in syntrophic acetate oxidation by cocultures
      of Geobacter sulfurreducens and Wolinella succinogenes.
AB  - Syntrophic cocultures of Geobacter sulfurreducens and Wolinella succinogenes
      oxidize acetate with nitrate as terminal electron acceptor. It has been
      postulated earlier that electrons are transferred in these cocultures not via
      hydrogen, but via a different carrier, e.g., a small c-type cytochrome that is
      detected in the supernatant of growing cultures. In the present study, L 
      cysteine, which was provided as a reducing agent, was found to mediate the
      electron transfer between the two partners. Low concentrations of L -cysteine or
      L -cystine (10-100 microM) supported syntrophic growth, and no acetate oxidation
      was observed in the absence of cysteine or cystine. Cell suspensions of G.
      sulfurreducens or coculture cell suspensions reduced cystine to cysteine, and
      suspensions of W. succinogenes or coculture suspensions oxidized cysteine with
      nitrate, as measured by the formation or depletion of free thiol groups. Added
      cysteine was rapidly oxidized by the coculture during growth, but the formed
      cystine was not entirely rereduced even under acceptor-limited conditions. The
      redox potential prevailing in acetate-oxidizing cocultures was -160 to -230 mV.
      Sulfide at low concentrations supported syntrophic growth as well and could
      replace cysteine. Neither growth nor acetate degradation was found with D
      cysteine, homocysteine, cysteamine, 3-mercaptopropionate, dithiothreithol,
      thioglycolate, glutathione, coenzyme M, dimethylsulfoxide, trimethylamine- N
      oxide, anthraquinone-2,6-disulfonate, or ascorbate.

PMID- 12070770
TI  - Intracellular localization of the particulate methane monooxygenase and methanol
      dehydrogenase in Methylomicrobium album BG8.
AB  - The methanotrophic bacterium Methylomicrobium album BG8 uses methane as a sole
      source of carbon and energy. This bacterium forms an extensive intracytoplasmic
      membrane. The first enzymes of the methane oxidation pathway are the membrane
      bound particulate methane monooxygenase and the periplasmic methanol
      dehydrogenase. Immunoelectron microscopy with specific antibodies was used to
      localize these enzymes to the intracytoplasmic membrane.

PMID- 12070771
TI  - Aciduric Proteobacteria isolated from pH 2.9 soil.
AB  - Acidic (pH 2.9) soil was used as an inoculum to culture heterotrophic bacteria at
      pH values of 3-4. Four isolates were obtained; on the basis of 16S rDNA sequence,
      they were shown to be members of the beta- and gamma-Proteobacteria. The three
      isolates that were most closely related to Burkholderia spp. had simple
      nutritional requirements and could grow in glucose-mineral salts media; two of
      these used a broad array of organic substrates. The 16S rDNA sequence of the
      fourth isolate was most similar (96%) to Frateuria aurantia. The isolates were
      aciduric rather than acidophilic; their pH ranges for growth were approximately
      3.5-8. Unlike many bacteria whose acid tolerance represents the capacity to
      survive acid exposure, these microorganisms carried out exponential growth at
      pH<4 and their growth rates at pH 3.9 ranged from 60 to 98% of those found at pH
      7. The cell yields on glucose of two strains were identical at pH 4 and pH 7. The
      acidic soils appeared to contain a very diverse bacterial community as assessed
      by denaturing gradient gel electrophoresis fingerprinting of PCR amplicons of a
      portion of the 16S rDNA gene. Electronic supplementary material to this paper can
      be obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00203-002-0427-1.

PMID- 12070772
TI  - Purification and characterization of an NADH oxidase from Eubacterium ramulus.
AB  - An NADH oxidase from the strictly anaerobic Eubacterium ramuluswas purified to
      homogeneity. The enzyme is composed of two types of subunits with molecular
      masses of 40 and 30 kDa. The molecular mass of the native enzyme is 450 kDa
      according to gel filtration and PAGE analysis. Six to eight mol of FAD were found
      per mol of native enzyme. The NADH-specific enzyme was inhibited by N
      bromosuccinimide and sulfhydryl reagents such as N-ethylmaleimide, CuCl(2) or
      ZnCl(2). The physiological function of the purified enzyme is unclear, but the
      demonstration of NADH-dependent O(2)-consumption suggests that it plays a role in
      the scavenging of oxygen.

PMID- 12070774
TI  - How RAGE turns in rage.

PMID- 12070775
TI  - Genetic dissection of host immune response.

PMID- 12070776
TI  - RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response.
AB  - The receptor for advanced glycation end products (RAGE) and its proinflammatory
      S100/calgranulin ligands are enriched in joints of subjects with rheumatoid
      arthritis (RA) and amplify the immune/inflammatory response. In a model of
      inflammatory arthritis, blockade of RAGE in mice immunized and challenged with
      bovine type II collagen suppressed clinical and histologic evidence of arthritis,
      in parallel with diminished levels of TNF-alpha, IL-6, and matrix
      metalloproteinases (MMP) 3, 9 and 13 in affected tissues. Allelic variation
      within key domains of RAGE may influence these proinflammatory mechanisms,
      thereby predisposing individuals to heightened inflammatory responses. A
      polymorphism of the RAGE gene within the ligand-binding domain of the receptor
      has been identified, consisting of a glycine to serine change at position 82.
      Cells bearing the RAGE 82S allele displayed enhanced binding and cytokine/MMP
      generation following ligation by a prototypic S100/calgranulin compared with
      cells expressing the RAGE 82G allele. In human subjects, a case-control study
      demonstrated an increased prevalence of the 82S allele in patients with RA
      compared with control subjects. These data suggest that RAGE 82S upregulates the
      inflammatory response upon engagement of S100/calgranulins, and, thereby, may
      contribute to enhanced proinflammatory mechanisms in immune/inflammatory
      diseases.

PMID- 12070777
TI  - Tyrosine 759 of the cytokine receptor gp130 is involved in Listeria monocytogenes
      susceptibility.
AB  - Interleukin-6 family cytokines have been implicated in adaptive and innate
      immunity, hematopoiesis, and inflammation. This cytokine family shares a signal
      transducing receptor subunit called gp130. gp130(F759/F759) knockin mice carry a
      point mutation at the SHP2-binding site of gp130 due to the replacement of
      tyrosine-759 (Y759 for human gp130) with phenylalanine (F). To explore the effect
      of this point mutation on the host response to bacterial infection,
      gp130(F759/F759) knockin mice were infected with Listeria monocytogenes.
      gp130(F759/F759) knockin mice began to die at 3 to 4 days post infection (p.i.)
      and showed higher mortality than did controls. Listeria titers at 3 days p.i. in
      the peritoneal cavity, spleen, and liver were significantly higher in
      gp130(F759/F759)knockin mice than in controls. Nitric oxide production,
      upregulation of the mRNA levels of a variety of cytokines, and listericidal
      activity in gp130(F759/F759) macrophages were unchanged. However,
      gp130(F759/F759) knockin mice displayed significantly lower levels of interferon
      (IFN)gamma in serum and in the culture supernatant from peritoneal exudate cells
      and splenocytes, in response to Listeria infection. These results suggest that
      the Y759 point mutation in gp130 attenuates the early phase of defense against
      Listeria infection, possibly owing to insufficient elevation of IFNgamma levels,
      and thus gp130 is a possible candidate gene for Listeria susceptibility.

PMID- 12070778
TI  - Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and
      DBA/2.
AB  - The ratio of CD4 T cells to CD8 T cells (CD4:CD8 ratio) varies over two-fold
      between C57BL/6 and DBA/2 mice for both T cell precursors in the thymus and
      mature T cells in the periphery. Correlation analysis of the CD4:CD8 ratio in
      thymic precursors vs peripheral T cells in F2 and backcross mice found that
      thymic precursor ratios are inherited independently from those in the periphery,
      indicating that the CD4:CD8 ratios in these populations are affected by distinct
      genetic mechanisms. A genome scan of progeny in the phenotypic extremes
      identified three quantitative trait loci (QTLs). Trmq1 (for T cell ratio modifier
      QTL 1) was detected in the telomeric end of c6 (peak marker D6Mit15 at 74 cM) and
      had a maximum LOD score of 4.6. Trmq2, in the telomeric half of c2, peaked at
      D2MIT483 and had a maximum LOD score of 3.41. Both of these QTLs impacted the
      CD4:CD8 ratios in peripheral T cells and had no impact on variation in this ratio
      among thymic precursors. However, heterozygosity for the H2 complex was
      suggestively associated (LOD score of 2.43) with increases in CD4 T cells among T
      cell precursors in the thymus. All of these QTLs were affected by epistatic
      interactions, indicating that additional modifiers in the B6 and DBA/2 genomes
      modulate this phenotype.

PMID- 12070779
TI  - Polymorphisms in the Il12b gene affect structure and expression of IL-12 in NOD
      and other autoimmune-prone mouse strains.
AB  - Interleukin (Il)-12 is a heterodimeric cytokine composed of 35 and 40 kD chains
      that plays a key role in the induction of Th1 cells, a T cell subset involved in
      many autoimmune diseases. We report here the cDNA sequence encoding the IL-12 p40
      subunit from the autoimmune-prone non-obese diabetic (NOD) mouse, which
      spontaneously develops type 1 diabetes. Compared with the C57BL/6 sequence, there
      are two base changes that lead to amino acid replacements. Other autoimmune-prone
      strains, but not the diabetes-resistant NOR strain, share the same allele as NOD.
      We found both trans- and cis- allele-dependent effects on levels of basal and
      induced IL-12p40 expression. Furthermore, we show that one of these changes
      results in a structural change in the p40 molecule, as evidenced by the failure
      of a monoclonal antibody to bind NOD IL-12. These findings have implications for
      the predisposition to autoimmune responses in NOD and other autoimmune-prone
      mouse strains.

PMID- 12070780
TI  - The CD23a and CD23b proximal promoters display different sensitivities to
      exogenous stimuli in B lymphocytes.
AB  - The single human CD23 gene encodes two protein products differing by six or seven
      amino acids in the extreme N-terminal cytoplasmic domain. The patterns of
      expression of CD23a and CD23b transcripts differs as a function of cell type and
      cell stimulation, with expression of CD23a being largely restricted to B cells
      and CD23b synthesis being inducible in a variety of haematopoietic cells by a
      range of exogenous stimuli. In this study, short defined sequences of the CD23a
      and CD23b proximal promoter regions were used to drive expression of exogenous
      reporter genes in transiently-transfected B cells exposed to a range of cellular
      stimuli. The CD23a promoter was activated only by IL-4, whereas the CD23b
      promoter was stimulated not only by IL-4, but also by stimulation with anti-mu,
      and anti-CD40. Deletion mutant analysis illustrated that of the two putative
      STAT6 binding sites present in the CD23a proximal promoter, deletion of the first
      site abrogated IL-4-driven transcriptional activation. Conversely, deletion of
      both STAT6 binding sites in the CD23b promoter was required before IL-4
      sensitivity was lost. When the same CD23b promoter mutants were studied in the
      context of anti-CD40 and anti-mu stimulation of transfected cells, deletion of
      the NF-kappaB site abrogated anti-CD40-driven transcriptional activation, but not
      anti-mu-mediated effects which required additional deletion of putative AP1 sites
      lying close to the CD23b initiator methionine codon. The data of this report are
      consistent with the interpretation that the upstream regions of the CD23a and
      CD23b isoform coding sequences show distinct sensitivities to agents which induce
      CD23 protein expression at the plasma membrane, and that transcriptional
      activation by discrete stimuli reflects activation of particular transcriptional
      regulatory factors.

PMID- 12070781
TI  - A single nucleotide polymorphism in the proximal IFN-gamma promoter alters
      control of gene transcription.
AB  - Interferon-gamma (IFN-gamma) is an important cytokine that regulates cellular
      immune responses to intracellular pathogens and neoplasia. Regulation of IFN
      gamma expression is stringently controlled at the transcriptional level. In this
      report we describe two novel single nucleotide polymorphisms (SNPs); one, at -179
      in the promoter, occurs in 4% of African Americans. This SNP represents a
      guanidine to thymidine transition and creates a potential AP-1 binding element.
      Electrophoretic mobility shift analysis reveals a unique complex binding to an
      oligonucleotide containing the variant -179T but not to the -179G using nuclear
      extracts from human peripheral blood T cells. In reporter gene assays, T cell
      lines transfected with the variant -204(179T) IFN-gamma promoter show a six to 13
      fold induction of luciferase activity in response to TNF-alpha over the common 
      204(179G) construct. The -179T allele identified in the proximal IFN-gamma
      promoter confers TNF-alpha inducibility and may prove important in human immune
      disorders and responsiveness to pathogens.

PMID- 12070782
TI  - A functional promoter polymorphism in the macrophage migration inhibitory factor
      (MIF) gene associated with disease severity in rheumatoid arthritis.
AB  - The macrophage migration inhibitory factor (MIF) is a potent pro-inflammatory
      cytokine and regulates the anti-inflammator effects of glucocorticoids. An
      important role for MIF within the cytokine cascade is to act in concert with
      endogenous glucocorticoids to control the set-point and magnitude of the
      inflammatory response. Elevated expression of MIF in the circulation and in the
      synovial joint has been documented in rheumatoid arthritis. MIF also has been
      linked to the development of joint damage and disease pathology in experimental
      animal models. We describe herein a novel CATT-tetranucleotide repeat
      polymorphism at position -794 of the human Mif gene and show that it functionally
      affects the activity of the MIF promoter in gene reporter assays. We describe
      four genotypes which comprise 5, 6, 7, or 8-CATT repeat units and show that the 5
      CATT allele has the lowest level of basal and stimulated MIF promoter activity in
      vitro. The presence of the low expressing, 5-CATT repeat allele correlated with
      low disease severity in a cohort of rheumatoid arthritis patients.

PMID- 12070783
TI  - Sticky and promiscuous plasma proteins maintain the equilibrium between bleeding
      and thrombosis.
AB  - A vascular fissure requires a patch that must be provided by constituents of the
      cellular and fluid phases of flowing blood. The principal components involved in
      primary haemostasis are platelets, collagen and von Willebrand factor (vWF).
      Platelets, the cellular elements of the patch, are inert until they encounter
      conditions that trigger their activation. Platelet adhesion and aggregation at
      the site of vascular injury lead to the formation of a platelet plug and to a
      local activation of the coagulation cascade. The resulting final product of blood
      coagulation is a fibrin network that stabilises the primary platelet plug. Most
      coagulation factors are zymogens of serine proteases. They are converted from an
      inactive form to an active enzyme by limited proteolytic cleavage of one or a few
      peptide bonds. The coagulation reactions must become extinguished as soon as the
      patch in the injured blood vessel has been established. Several inhibitors,
      present in excess in plasma, neutralise the surplus of remaining proteases, and
      the fibrinolytic system dissolves the plug after the surrounding tissue has been
      repaired. In fulfilling their function to control the fluidity and integrity of
      the vascular system, the plasmatic and cellular haemostatic players undergo
      multiple interactions of two kinds: they recognize and bind, often irreversibly,
      to several partners which are present in their immediate environment. On the
      other hand, some haemostatic factors, such as fibrinogen and von Willebrand
      factor, enhance their stickiness by polymerisation of identical subunits carrying
      multiple adhesive sites. Several haemostatic plasma proteins and their cellular
      surface receptors are involved in or may be affected by other homeostatic
      systems, such as immune response, complement activation, cytokine release, cell
      proliferation, growth and differentiation. These diverse functions are only
      possible because of the modular structure of participating proteins. In the
      process of evolution a series of structural modules have been incorporated into
      protein molecules as their integral domains by exon duplication and shuffling.
      Owing to variable conformations of the resulting multi-domain proteins, the same
      modules may perform different tasks and be recognized only by specific ligands,
      thus controlling the delicately balanced system of haemostasis.

PMID- 12070784
TI  - DNR orders at a tertiary care hospital--are they appropriate?
AB  - QUESTIONS UNDER STUDY: There are no established recommendations in Switzerland on
      when, how and for what patients DNR orders should be written. Moreover, little is
      known about current attitudes, patients' preferences, patients' involvement in
      decision-making and the adequacy of such decisions. The study was conducted in a
      Swiss tertiary care hospital to investigate the epidemiology, manner of
      application and appropriateness of DNR orders. METHODS: We performed
      retrospective chart review of all patients admitted to the department of general
      internal medicine of a Swiss tertiary care university hospital during four
      randomly selected months of the year 1998 (group 1) as well as of all patients
      who died in the department during 1998 (group 2). We assessed the frequency of
      DNR orders on admission and before death, their association with age, sex,
      diagnostic category, comorbidity and physical/social dependence, and the
      frequency of patient and/or family involvement in decision-making. RESULTS: On
      admission, a DNR order was written for 15% of all hospitalised patients and 54%
      of the patients dying during the observation period; 93% of patients ultimately
      dying were the subject of DNR orders before death. There was a significant
      association between DNR orders and patients' age (p <0.001), physical and/or
      social dependence (p <0.001) and the admission diagnoses malignancy (p <0.001) or
      acute stroke (p <0.005). Cardiovascular disease was in inverse ratio to DNR
      orders (p <0.001). Only 6% of either patients or families were reportedly
      involved in decisions in the overall group, whereas this was the case in 58% of
      patients who died in hospital. CONCLUSIONS: The frequency of DNR orders on
      admission was rather high. Referring to pre-arrest morbidity, DNR orders were
      often inappropriate on hospital admission but usually became so during hospital
      stay. After exclusion of confounding factors, age was the main independent factor
      for DNR orders. Patient and/or surrogate involvement in decision-making for DNR
      orders was low, thereby raising important ethical issues such as patient
      autonomy. An urgent national discussion on the topic is needed.

PMID- 12070785
TI  - Screening and treatment for latent tuberculosis infection among asylum seekers
      entering Switzerland.
AB  - AIM OF THE STUDY: To evaluate the compliance of doctors and patients with the
      current recommendations for screening and preventive treatment of immigrants with
      a positive tuberculin skin test (TST) suggestive of latent tuberculosis infection
      (LTBI). METHODS: Retrospective cohort study of all asylum seekers entering
      Switzerland between 1 January 1993 and 31 December 1993 and assigned to the
      cantons of Aargau, Fribourg, Geneva, Neuchatel, Valais and Vaud, who underwent a
      TST at the border. The medical documents of all individuals with a TST size
      suggestive of LTBI (> or = 10 mm in children <15 years, > or = 18 mm in young
      adults aged 15-25 years) were reviewed for final diagnosis, therapeutic decision,
      compliance with treatment if prescribed, and notification for tuberculosis within
      the next 3 years. RESULTS: Among 2515 asylum seekers, 172 had a positive TST
      suggestive of LTBI. The documents of 93 persons were available. The final
      diagnosis was LTBI in 71 cases, possible tuberculosis in 10 cases, an effect of
      BCG immunisation in 10 cases, and other diagnoses in 2 cases. Among 82
      individuals with normal chest X-ray or no radiological examination, only 37 (46%)
      received a preventive treatment and one a full course of antituberculosis drugs.
      Among 11 persons with an abnormal chest X-ray, 2 received a full course of
      antituberculosis drugs, 7 a preventive therapy and 2 had no treatment prescribed.
      Among the 44 subjects in whom a preventive treatment was prescribed, 30 adhered
      to the treatment regimen. One case (without prescribed treatment) was notified
      for tuberculosis two years after entry. CONCLUSIONS: Compliance of doctors and
      patients with current recommendations for examination and treatment of immigrants
      with a TST suggestive of LTBI is unsatisfactory. New guidelines are needed to
      provide a clearer definition of the indications and explain the benefits of
      treating LTBI.

PMID- 12070786
TI  - Are internists in an non-prescriptive setting favourable to guidelines? A survey
      in a Department of Internal Medicine in Switzerland.
AB  - A cross-sectional anonymous postal survey was carried out in a Department of
      Internal Medicine in order to assess physicians' knowledge about and attitudes
      towards clinical practice guidelines and to evaluate the role of age in
      determining their use and opinions. The study took place in a Swiss University
      Hospital where exposure to guidelines had been limited. The questionnaire was
      sent to the 174 physicians of the Department. The response rate was 67%
      (116/174). The spontaneous definitions of guidelines were heterogeneous and
      referred to information of uncertain validity. Most participants, especially the
      younger groups of junior and senior residents, reported using guidelines and were
      favourable to their development. Less favourable attitudes were observed among
      senior staff physicians and consultants. For instance, the latter more often held
      the opinion that guidelines are too rigid to apply to individual patients, were
      likely to decrease physician reimbursement and to hamper research (respectively,
      32% vs 24%, 50% vs 31% and 18% vs 7% when compared with the opinions of
      residents). In conclusion, in a non-prescriptive hospital setting, where the
      development, dissemination and implementation of guidelines are emerging, the
      concept of 'guideline' was heterogeneous. Despite generally positive attitudes
      towards guidelines, the opinion of senior staff physicians constitute a barrier
      to their dissemination and implementation.

PMID- 12070787
TI  - Bronchial provocation tests: the rationale for using inhaled mannitol as a test
      for airway hyperresponsiveness.
AB  - The use of histamine and methacholine is well established for identifying airway
      hyperresponsiveness (AHR) but the AHR to these agents is not specific for asthma
      diagnosis. Further, these agents do not identify or exclude exercise-induced
      asthma (EIA) so they are inappropriate for some occupational and sporting
      assessments. Measurement of AHR by pharmacological agents has other limitations
      in that a positive response does not necessarily identify a person who will
      respond to inhaled steroids and responses do not differentiate between doses of
      steroids. As most asthmatics remain hyperresponsive to these agents after
      treatment they have not been useful for guiding steroid dose reduction. Bronchial
      provocation tests (BPTs) with physical stimuli such as exercise, eucapnic
      voluntary hyperpnea and hypertonic saline have provided useful information on
      presence and severity of asthma and EIA. These tests however, can be time
      consuming and require more resources compared with the pharmacological tests. To
      simplify testing, a challenge has been developed that uses a dry powder of
      mannitol administered from a simple hand-held device. The mannitol is given in
      increasing doses from capsules containing from 5 mg to 40 mg. Mannitol
      responsiveness identifies people with EIA and those who will respond to inhaled
      steroids. Mannitol responsiveness is reduced following treatment with inhaled
      steroids, and some subjects become unresponsive within 6 to 8 weeks.
      Responsiveness to mannitol can be used to predict risk of exacerbation during
      back titration of steroids. Should this BPT become more readily available it
      would be the first to provide a common operating standard for use in the
      laboratory, office, or field.

PMID- 12070788
TI  - Impaired sensorimotor gating in schizophrenia with deficit and with nondeficit
      syndrome.
AB  - QUESTIONS UNDER STUDY: Prepulse inhibition (PPI) is the normal suppression of the
      startle reflex when the intense startling stimulus is preceded by a barely
      detectable prepulse. PPI has been proposed to reflect a measure of sensorimotor
      gating or filtering. Deficits in PPI has been found in schizophrenia in various
      prepulse conditions. The aim of this study was to investigate whether deficits in
      particular prepulse conditions relate to psychopathological syndromes. METHODS:
      Schizophrenia was subgrouped into patients with deficit and with nondeficit
      syndrome using the schedule of Kirkpatrick. Schizophrenia with deficit syndrome
      (N = 46), schizophrenia with nondeficit syndrome (N = 21), and controls (N = 44)
      were compared in an acoustic startle paradigm assessing PPI (30, 60, 120, 240 and
      2000 ms interstimulus intervals). A mixed ANOVA was used to analyse the PPI-data.
      RESULTS: Schizophrenia with deficit syndrome showed a PPI-deficit in the 60 ms
      prepulse condition and a reduced facilitation in the 2000 ms prepulse condition,
      whereas PPI in patients with nondeficit syndrome was impaired in the 240 ms
      prepulse condition. CONCLUSIONS: The different patterns of PPI in deficit and
      nondeficit patients appear to relate to the heterogeneity of schizophrenia. Thus,
      this study may explain the various findings in previous PPI studies in the field
      of schizophrenia.

PMID- 12070789
TI  - Psychosomatic liaison service in medicine - need for psychotherapeutic
      interventions and their realisation.
AB  - QUESTIONS UNDER STUDY: The aim of the study was to evaluate the need for
      psychotherapeutic interventions and their realisation within the framework of the
      psychosomatic liaison service. Apart from establishing the diagnosis of
      psychosocial distress and mental disorders, we assessed the motivation of the
      patients for psychotherapy. METHODS: 62 consecutive patients admitted to the
      Department of Medicine (Gastroenterology and Hepatology) Freiburg University
      Hospital, Freiburg, Germany, underwent standardised psychodiagnostic interviews
      and completed psychometric self-rating tests to identify mental disorders,
      psychosocial distress, and motivation for psychotherapy. In addition, the
      patients' need for psychotherapeutic treatment was rated by the liaison
      therapist. RESULTS: Using ICD 10-criteria, mental disorders were diagnosed in two
      thirds of the patients; most frequent were adjustment disorders, affective
      disorders, and disorders resulting from alcohol use. One third of the patients
      reported signs of psychological distress; half of them were interested in
      psychotherapy. A need for psychotherapeutic interventions, based on motivation of
      the patients and on expert estimate, was found in approximately one third of the
      patients. 36% received actual psychotherapy. CONCLUSIONS: Our study suggests that
      - in the patient population studied - the patients' motivation ought to be taken
      into consideration more strongly when evaluating the need for psychotherapy in
      clinical practice and further research.

PMID- 12070791
TI  - [To our readers].

PMID- 12070790
TI  - Organic dust exposure in dairy farmers in an alpine region.
AB  - OBJECTIVES: Epidemological studies suggest that farmers are at an increased risk
      for chronic obstructive pulmonary disease because of exposure to organic dust. We
      assessed the proportion of farmers among patients with end stage lung disease and
      we measured the seasonal exposure of dairy farmers to organic dust in a rural
      alpine region in Switzerland. METHODS: Six dairy farms of different sizes and
      infrastructures were chosen for measurements of organic dust (PM10 = particles
      with a 50% cut-off aerodynamic diameter of 10 gm). Indoor measurements were
      performed during 3-5 days at each farm in late winter, summer and early winter of
      one year. RESULTS: 17 measurements of organic dust were carried out on 6
      different farms. The concentrations of PM10 ranged from 109-2207 microg/m3 for
      daily barn activities in winter months and from 76-4862 microg/m3 for hay storage
      in summertime. Exposure depended on farm infrastructure and season. It was higher
      in smaller and older cattle buildings and during the late winter months. The
      farmers were exposed to the measured amount of organic dust (PM10) for 5 to 6
      hours per day during the winter (approximately 900-1260 hours/year). CONCLUSIONS:
      The study confirms a moderate to high exposure to organic dust (PM10) in these
      farmers, which, together with epidemiological data, suggests that such exposure
      over many years could be a major risk factor for the development of chronic
      obstructive pulmonary disease in dairy farmers.

PMID- 12070792
TI  - [The overweight and underweight girl: from findings to prevention].
AB  - Both preponderance as well as underweight normally starts in childhood and
      puberty and hurt the fate of young women mostly a life long. Weight and fat
      tissue as an energy storage regulates through the hormone Leptin appetite, food
      intake and therefore the energy reserves. With this hormone exist a common
      pathophysiological regulation unit, which causes in case of preponderance an
      increased, in case of underweight a decreased cyclus activity. Besides short term
      influences (like the development of the PCO-syndrome and/or fatigue fractures)
      the long-term consequences especially the accumulation of the visceral fat, the
      cardio-vascular diseases, metabolic syndrome, type-II-diabetes, mammary- and
      endometrial carcinoma play a special role. On the other hand chronic underweight
      very frequently leads through chronic estrogen defect to osteopenia, osteoporosis
      and therefore to cyclus disturbances, sterility and osteoporosis. A simple
      finding like weight, has thus an important predictive quality for later illnesses
      and their prevention.

PMID- 12070793
TI  - [Quality of life: a new topic in medicine?].

PMID- 12070794
TI  - [Clinics online - strong lights cast deep shadows. How to shape profitable
      intensive hospital presentation with service design via internet].

PMID- 12070795
TI  - [Reliability of the Menopause Rating Scale (MRS): Investigation in the German
      population].
AB  - The Menopause Rating Scale (MRS) is a well accepted instrument to measure the
      severity of menopausal symptoms. As yet, however, investigations had not
      specifically been directed towards short-term test-retest reliability of the
      scale. The MRS was twice applied in a random sample of 45-65 years aged women of
      the German Cohort Study of Women's Health with a distance between the
      measurements of 14 days. The response rate in the sample was 70 %. The
      correlation coefficient (Pearson) of the sum-score of the two measurements was r
      = 0.82. The high repeatability of the test results confirms our clinical
      experience and emphasizes excellent practical applicability. The MRS can be
      recommended for the clinical practice as a reliable scale both for the
      measurement and long-term surveillance of menopausal complaint dynamics.

PMID- 12070796
TI  - [First experiences with human blastocyst culture after IVF/ICSI under the
      conditions of the German embryo protection law].
AB  - OBJECTIVE: Due to the improvements in human embryo culture in the recent years,
      it is now possible to transfer embryos five days after oocyte retrieval and IVF
      or ICSI at the blastocyst stage with favorable implantation rates. In Germany it
      is illegal to cultivate more than 3 embryos, therefore the selection has to be
      done at the pronuclear stage. There we report our experiences of human blastocyst
      culture in a routine IVF/ICSI programme under the conditions of the German Embryo
      Protection Law. MATERIALS AND METHODS: The data of 100 couples undergoing the IVF
      ICSI programme at the University Clinic of Wurzburg were analysed prospectively.
      14-18 hours after insemination or micro-injection two or three zygotes with the
      best pronuclear development were selected for further cultivation. Fertilized
      oocytes were cultured in sequential media and were then transferred into the
      uterus 5 days after oocyte recovery. The blastocysts were graded from 1-8.
      RESULTS: In 100 cycles a total of 859 oocytes were collected, of whom 663 were
      fertilized and reached the pronuclear stage (median fertilization rate 88.9 %).
      251 zygotes were selected at the PN stage. 51 % of the selected zygotes achieved
      the blastocyst stage after 5 days (grade 1-5), 28 % were morulae (grade 6-7) and
      21 % of the embryos arrested in their development (grade 8). The clinical
      pregnancy rate was 26 %. Women who conceived had a significant better development
      of blastocysts on day 5 (grade 4 versus grade 6, P < 0.01) than those not
      achieving pregnancy. CONCLUSIONS: In summary, under the current legal conditions
      in Germany, blastocyst culture cannot improve pregnancy rates as the rate of
      arrested embryos of over 20 % limits the chances of implantation.

PMID- 12070797
TI  - [Fears of pregnant women if prenatal examination yields or does not yield any
      findings].
AB  - OBJECTIVE: Besides a medical point of view, prenatal diagnosis also has
      psychological effects on the pregnant woman. We studied the state of anxiety
      before and after prenatal examination with unsuspicious and suspicious prenatal
      findings. MATERIAL AND METHODS: In a consecutive sample of 332 pregnant women
      presenting between the 12th and 21st week of gestation for prenatal malformation
      scan (level three reference centre, Unit for Prenatal Medicine, Department of
      Obstetrics and Gynaecology, Medical University of Lubeck) we ascertained state
      and trait anxiety (Spielberger) before prenatal examination and state anxiety
      after prenatal examination with unsuspicious and suspicious findings. RESULTS: In
      the sample of N = 332 pregnant women prenatal examination showed a suspicious
      finding in 37 fetuses (11.1 %) and an unsuspicious finding in 295 fetuses (88.9
      %). Before prenatal examination there is no difference (Mann-Whitney-Test, P =
      0.286) between the group with negative results and the pregnant women with a
      positive result for the trait anxiety scale; however, there is a significant
      difference (Mann-Whitney-Test, P = 0.014*) for the scale of state anxiety. After
      prenatal examination the evaluation of the state anxiety questionnaire shows a
      significant (Mann-Whitney-Test, P = 0.000*) difference between pregnant women
      with an unsuspicious finding and pregnant women with a suspicious finding. State
      anxiety is significantly reduced after examination if the prenatal scan is
      unsuspicious (Wilcoxon-Test, P = 0.000*), but there is no significant difference
      between pre-and post-examination anxiety if there is a positive finding (Wilcoxon
      Test, P = 0.399). Evaluating aspects of anxiety as regards content, it can be
      demonstrated that before prenatal examination the pregnant women are just as much
      afraid of a malformation being detected as of it being missed. CONCLUSIONS:
      Suspecting or knowing about a malformation of the unborn means a complex process
      of coping and an intense psychosocial strain for a pregnant woman. Besides the
      fear of a detected malformation the pregnant women state equal fear of a
      malformation being missed. In contrast to this the immediate feedback of a
      negative finding during ultrasound examination leads to a significant reduction
      of anxiety and to an emotional relief for the pregnant woman.

PMID- 12070798
TI  - [Expression of c-erbB-2 and topoisomerase II alpha in relation to chemoresistance
      in ovarian cancer].
AB  - In the present study, we examined die role of c-erbB-2 for chemoresistance in
      ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated
      with a shorter survival of patients with primary ovarian cancer (P = 0.0001, N =
      77) and was an independent prognostic factor in the proportional-hazard model (P
      = 0.035). A significant association between expression of c-erbB-2 mRNA und
      survival was obtained for the subgroup of patients who received a standard
      chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003). In
      addition, the application of a standard chemotherapy improved the survival of
      patients with relatively low c-erbB-2 expression (P = 0.013), but not of patients
      with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA
      correlated with expression of topoisomerase IIalpha mRNA determined by a reverse
      semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 und
      topoisomerase IIbeta mRNA dit not correlate (P = 0.221). The data suggest that
      topoisomerase IIalpha, which correlates with c-erbB-2 expression, contributes to
      the resistance of c-erbB-2-overexpressing carcinomas.

PMID- 12070799
TI  - Unrecognized cervical pregnancy treated by suction curettage and cervicovaginal
      tamponade.
AB  - The authors presented a case of a 30-year tertigravidar women with unrecognized
      cervical pregnancy, treated by suction curettage and cervicovaginal tamponade. In
      our case of unrecognized cervical pregnancy, during hysterometry and cervical
      dilatation occured uterine bleeding and clinical pictures of obstetrics
      hemorrhagic shock, so we continued with suction curettage and cervicovaginal
      tamponade as a urgent procedure which turned out as a final. Medicamentous
      chemotherapy of the cervical pregnancy (methotrexat) was not used, because after
      described procedure beta-HCG lytic decreased and without colour-Doppler
      visualization of local cervical trophoblastic vascularisation.

PMID- 12070801
TI  - Veterinary clinical pathology in industry: 2000 to 2020.

PMID- 12070802
TI  - Mechanism-based diagnostic reasoning: thoughts on teaching introductory clinical
      pathology.
AB  - Teaching introductory clinical pathology to veterinary students is a challenging
      endeavor that requires a shift in learning strategies from rote memorization to
      diagnostic reasoning. Educational research has identified discrete cognitive
      stages required to achieve the automated, unconscious thinking process used by
      experts. Building on this knowledge, we developed a case-based approach to
      clinical pathology instruction that actively engages students in the learning
      process and links performance with positive reward. Simulated cases provide
      context and create a structure, or "schema", which enhances the learning process
      by enabling students to synthesize facts and link them with their causal
      mechanism to reach a defensible diagnostic conclusion. Web-based tools, including
      the "Problem List Generator" and tutorials, have been developed to facilitate
      this process. Through the collaborative Biomedical Informatics Research Group, we
      are working to further develop and evaluate Web-based instructional tools and new
      educational methods, to clarify the diagnostic reasoning processes used by
      experienced clinical pathologists, and, ultimately, to better educate our future
      students to be effective diagnosticians.

PMID- 12070803
TI  - Discriminant and multiple regression analysis of anemia and opportunistic
      infection in Fell pony foals.
AB  - A condition resembling acquired immunodeficiency with anemia has been described
      in British Fell pony foals. The pathogenesis is unknown. The present study
      involved 322 foals of which 164 were of Fell breed and 12 were affected.
      Discriminant and multiple regression analyses were used to test the results of
      all clinical pathology parameters from these foals for statistical association
      with (1) breed origin and (2) presence of disease. Only hematocrit associated
      significantly with presence of disease. However, significant associations were
      found with Fell breed origin, including serum albumin concentration and
      lymphocyte count. The unexpected discovery of sporadic lymphocytosis in the breed
      indicates the value of this kind of analysis and may be evidence that Fell foal
      immunodeficiency is associated with retroviral infection.

PMID- 12070804
TI  - A mass in the spinal column of a dog.

PMID- 12070805
TI  - Idiopathic localized eosinophilic synovitis in a cat.
AB  - A 4-year-old male castrated Seal Point Himalayan cat was presented for evaluation
      of right thoracic limb lameness of 6 weeks duration. Synovial fluid analysis of
      the swollen right carpal joint revealed a mixed cell synovitis, with a total
      nucleated cell count of 13,200/microliter and 34% eosinophils. A diagnosis of
      idiopathic localized eosinophilic arthritis was made. Additional clinical and
      diagnostic findings included mild lymphadenopathy with lymphoid hyperplasia and
      an antinuclear antibody titer of 1:320. Lack of multisystem involvement made
      systemic lupus erythematosis unlikely. Immunosuppressive therapy with oral
      prednisone alleviated the lameness. Eosinophilic synovitis has not previously
      been reported in cats. An immune-mediated mechanism was likely in this case;
      however, the exact etiology remains unknown.

PMID- 12070806
TI  - Gastric lavage from a Madagascar tree boa (Sanzinia madagascarensis).

PMID- 12070800
TI  - A comprehensive analysis of recently integrated human Ta L1 elements.
AB  - The Ta (transcribed, subset a) subfamily of L1 LINEs (long interspersed elements)
      is characterized by a 3-bp ACA sequence in the 3' untranslated region and
      contains approximately 520 members in the human genome. Here, we have extracted
      468 Ta L1Hs (L1 human specific) elements from the draft human genomic sequence
      and screened individual elements using polymerase-chain-reaction (PCR) assays to
      determine their phylogenetic origin and levels of human genomic diversity. One
      hundred twenty-four of the elements amenable to complete sequence analysis were
      full length ( approximately 6 kb) and have apparently escaped any 5' truncation.
      Forty-four of these full-length elements have two intact open reading frames and
      may be capable of retrotransposition. Sequence analysis of the Ta L1 elements
      showed a low level of nucleotide divergence with an estimated age of 1.99 million
      years, suggesting that expansion of the L1 Ta subfamily occurred after the
      divergence of humans and African apes. A total of 262 Ta L1 elements were
      screened with PCR-based assays to determine their phylogenetic origin and the
      level of human genomic variation associated with each element. All of the Ta L1
      elements analyzed by PCR were absent from the orthologous positions in nonhuman
      primate genomes, except for a single element (L1HS72) that was also present in
      the common (Pan troglodytes) and pygmy (P. paniscus) chimpanzee genomes. Sequence
      analysis revealed that this single exception is the product of a gene conversion
      event involving an older preexisting L1 element. One hundred fifteen (45%) of the
      Ta L1 elements were polymorphic with respect to insertion presence or absence and
      will serve as identical-by-descent markers for the study of human evolution.

PMID- 12070807
TI  - Flow cytometric evaluation of canine bone marrow differential cell counts.
AB  - Three flow cytometric techniques were evaluated for determination of differential
      cell counts on canine clinical bone marrow specimens. Techniques included
      staining bone marrow specimens with 2'7'-dichlorofluorescein (DCF) or 3,3'
      dihexyloxacarbocyanine iodide (DiOC6) and evaluation of forward-angle light
      scatter vs. side-angle light scatter plots. Flow cytometric evaluation of bone
      marrow cells stained with DCF failed to separate bone marrow cells into distinct
      cell populations. Staining with DiOC6 resulted in separation of bone marrow cells
      into populations of mature and immature erythroid cells, mature and immature
      myeloid cells, and lymphocytes. The scatter plot method resulted in
      identification of mature and immature erythroid cells, immature myeloid cells,
      metamyelocytes, and bands and segmenters. Lymphocytes could not be differentiated
      from mature erythroid cells by the scatter plot method. When the results of the
      DiOC6 method and the scatter plot method were compared with manual bone marrow
      differential cell counts, the scatter plot method had more similar mean values
      and higher correlation coefficients. The scatter plot method has the potential of
      providing rapid semiquantitative assessment of bone marrow differential cell
      counts in dogs for specimens that contain low numbers of lymphocytes.

PMID- 12070808
TI  - A good prognosis for the future of laboratory diagnostics.

PMID- 12070810
TI  - Laryngopharyngeal mass in a dog with upper airway obstruction.

PMID- 12070809
TI  - Immunohistochemical characterization of estrogen and progesterone receptors in
      lymphoma of horses.
AB  - Immunohistochemical techniques were used to examine 29 cases of equine lymphoma
      for estrogen receptor (ER) and progesterone receptor (PR) expression. The
      lymphomas examined included T-cell-rich large B-cell lymphomas, B-cell neoplasms,
      and T-cell lymphomas. The individual cases were also classified according to the
      anatomic location of the tumors. One normal equine lymph node was also examined
      for ER and PR expression. All of the cases of equine lymphoma and the normal
      lymph node were negative for Er. A total of 16/29 (55%) PR-positive lymphomas
      were identified. Seven of the 12 (58%) T-cell-rich large B-cell lymphomas were
      positive, 7/11 (64%) B-cell tumors were positive, and 2/6 (33%) T-cell neoplasms
      were positive. Anatomically, 6/9 (66%) subcutaneous lymphomas were PR positive,
      3/5 (60%) intrathoracic lymphomas were positive, 1/4 (25%) intra-abdominal
      lymphomas were positive, 2/5 (40%) intra-abdominal/intrathoracic lymphomas were
      positive, 1/2 (50%) upper airway lymphomas were positive, and 3/3 (100%) splenic
      lymphomas were positive. One case involving abdominal and thoracic tumors and
      leukemia was negative for PR expression. The normal lymph node contained a low
      percentage (1.9%) of PR-positive lymphocytes. The presence of PR in neoplastic
      equine lymphoid tissue indicates that these tumors may be responsive to serum
      progesterone. Also, identification of PR-positive cells in the normal lymph node
      suggests that PR may be constitutively expressed in normal equine lymphocytes.
      Further studies are needed to quantify PR levels in normal and malignant equine
      lymphoid tissue and to determine the usefulness of either progestin or
      antiprogestin drugs in the management of equine lymphoma.

PMID- 12070811
TI  - Validation of an immunoturbidimetric D-dimer assay in canine citrated plasma.
AB  - D-dimer is a neoantigen formed when thrombin initiates the transformation of
      fibrinogen to fibrin; it is derived from plasmin digestion of cross-linked
      fibrin. In human medicine, the usefulness of this analyte in diagnosing
      disseminated intravascular coagulation (DIC) has been assessed in patients
      fulfilling the clinical and laboratory requirements for this disorder. In canine
      medicine, the use of D-dimer is relatively new. Detailed studies are needed to
      understand the relationship between D-dimer concentration in plasma and DIC
      status in dogs. We validated a D-dimer immunoturbidimetric assay (Tina-quant [a]
      D-Dimer, Boehringer Mannheim) in canine citrated plasma samples. Intra-assay and
      interassay variability (coefficient of variation) was 5.63% and 8.82%,
      respectively. The assay was linear, using 2 samples with low and high D-dimer
      concentrations (r=.996 and.998). Accuracy was 102.2% and 95.7% based on a
      recovery study in which 2 samples were assessed. Reference values for D-dimer
      were established using 70 healthy dogs that were assessed clinically and
      evaluated on the basis of a complete laboratory workup. The reference range was
      set between 0.02 and 0.28 microgram/mL (chi-square test for normal distribution,
      P>.05).

PMID- 12070812
TI  - Pleural effusion in a dog.

PMID- 12070813
TI  - Bone marrow aspirate from a dog with anemia and thrombocytopenia.

PMID- 12070814
TI  - Hematologic evaluation of normal and anemic lambs with the Technicon H*1 using
      EDTA or heparin as anticoagulants.
AB  - A study was performed to evaluate blood from young lambs using the Technicon H*1
      hematology analyzer, with emphasis on RBC parameters, comparison of tripotassium
      EDTA and heparin, and the effects of storage on heparinized blood. Blood samples
      from lambs 2 days to 18 weeks of age were analyzed within 6 hours, revealing a
      high precision, except for WBC counts in heparinized blood. The HCT values
      estimated by the H*1 correlated well (r(2)=.90) with those obtained by the
      microhemotocrit method. Mean hematologic values obtained for heparinized blood
      differed by up to 4% from values obtained from blood collected into EDTA. WBC
      counts decreased 8.5% in heparinized blood stored at 4 degrees C for 1 day, but
      differences observed in RBC counts were </= 2%. Problems occurred when analyzing
      blood from young lambs with low hemoglobin values because the H*1 incorrectly
      counted microcytes with volumes of < 10 fL as platelets. When the necessary
      corrections were performed, the H*1 was useful for analyzing RBC parameters in
      lamb blood collected both into EDTA and into heparin.

PMID- 12070815
TI  - Mixed venous and arterial blood in bovine coccygeal vessel samples for blood gas
      analysis.
AB  - Bovine coccygeal (median, caudal) vessel samples are not always venous in origin
      but may be arterial or a mixture of venous and arterial blood. Results of blood
      gas analysis of blood samples collected from 39 cows were consistent with typical
      venous, mixed venous-arterial, or typical arterial blood. This observation was
      made while establishing reference intervals for a new blood gas instrument. The
      pO2 and the oxygen saturation of hemoglobin (S02) were most reflective of the
      amount of arterial blood contamination in the sample, but pCO2 and pH also were
      altered. The pO2 values ranged from 21 to 127 mm Hg, and SO2 ranged from 35% to
      100%. The mean pCO2 in venous type samples was 46.3 mm Hg compared to 36.7 mm Hg
      in arterial type samples. The mean pH in venous type samples was 7.42 compared to
      7.47 in arterial type samples.

PMID- 12070816
TI  - Hematology and plasma chemistry reference intervals for cultured tilapia
      (Oreochromis hybrid).
AB  - Tilapia are a commonly aquacultured fish yet little is known about their normal
      physiology and response to disease. In this study we determined the results of
      complete hematologic (n=40) and plasma biochemical profiles (n=63) in production
      tilapia (Oreochromis hybrids). The fish were raised in recirculating systems with
      a high stocking density (120 g/L), and were in the middle of a 15-month
      production cycle. Blood was analyzed using standard techniques, and reference
      intervals were determined using nonparametric methods. Non-production tilapia
      (n=15) from low-density tanks (4 g/L) also were sampled; the clinical chemistry
      results were compared to reference intervals from the fish raised in high-density
      tanks. Differences were noted in plasma protein, calcium and phosphorus
      concentrations, such that reference intervals for high-density production tilapia
      were not applicable to fish raised under different environmental and management
      conditions.

PMID- 12070817
TI  - Popliteal lymph node aspirate from a dog with a maxillary mass.

PMID- 12070818
TI  - Effect of temperature, storage time, and sample type on sorbitol dehydrogenase
      activity in llama serum and plasma.
AB  - Serum and heparinized plasma samples were collected from 11 adult, clinically
      healthy llamas. Aliquots were assayed for sorbitol dehydrogenase (SDH) activity
      after storage at room temperature (20 degrees C), 4 degrees C, or -20 degrees C
      for defined time intervals up to 1 week postcollection. Sorbitol dehydrogenase
      activity in all samples was within reference intervals for our laboratory. No
      difference was found between serum and plasma SDH activity when measured
      immediately (within 1 hour) after collection. Sorbitol dehydrogenase activity
      decreased to 79% of initial activity by 24 hours in serum stored at room
      temperature; plasma had 94% of initial SDH activity under the same conditions.
      Sorbitol dehydrogenase activity was stable in both plasma and serum stored for up
      to 1 week at 4 degrees C or -20 degrees C. With the exception of serum stored at
      20 degrees C for > 8 hours, in vitro stability of llama SDH was adequate or its
      use in diagnostic testing.

PMID- 12070819
TI  - Mediastinal mass in a dog with syncope and abdominal distension.

PMID- 12070820
TI  - Effect of specimen collection and storage on blood glucose and lactate
      concentrations in healthy, hyperthyroid and diabetic cats.
AB  - The objective of this study was to compare and investigate differences in glucose
      and lactate concentrations in sodium fluoride/potassium oxalate (NaF/Ox) plasma
      and serum in healthy cats and cats with metabolic disease. Glucose and lactate
      concentrations were determined in routinely processed serum and NaF/Ox plasma
      obtained from healthy (n=30), hyperthyroid (n=27) and diabetic (n=30) cats, and
      in samples from 6 healthy cats stored at 25 degrees C or 4 degrees C for 0, 1, 2,
      4, or 8 hours. The packed cell volume (PCV) of blood collected in NaF/Ox was
      compared with that of blood collected in EDTA. Mean glucose concentration was
      significantly (P<.05) lower in NaF/Ox plasma than in serum in all groups of cats,
      by 0.7-2.5 mmol/L (11-45 mg/dL); the difference was greater in hyperthyroid and
      diabetic cats. In vitro, only serum stored on the clot for >/= 1 hour at 25
      degrees C had significantly lower glucose and higher lactate concentrations. The
      PCV of NaF/Ox-anticoagulated blood was lower that that of EDTA-anticoagulated
      blood, by 7.0% +/- 1.4% (P<.01). In conclusion, collection of feline blood in
      NaF/Ox was necessary to prevent in vitro increases in lactate concentration;
      however, NaF/Ox artifactually decreased plasma glucose concentration because of
      RBC shrinkage. The PCV should not be determined on blood collected in NaF/Ox.

PMID- 12070821
TI  - A comparison of the cytologic and histologic features of meningiomas in four
      dogs.
AB  - The cytologic and histologic features of 2 intracranial and 2 spinal
      (extramedullary cervical) canine meningiomas were compared. Cerebrospinal fluid
      analysis in 2 cases revealed mild, mixed cell pleocytosis, primarily composed of
      small lymphocytes and monocytoid cells, with a moderate increase in total protein
      concentration. Cytologic features suggestive of meningioma included cells with
      both epithelial and mesenchymal characteristics and a tendency towards cell
      clustering. Tumor location also was useful in making a diagnosis. The 4
      meningiomas differed histologically from one another, and included angioblastic,
      psammomatous, meningotheliomatous, and microcystic anaplastic types, which
      conformed to a classification scheme for human meningiomas. The classification
      scheme could not be applied to cytologic specimens.

PMID- 12070823
TI  - Aspirate of an elbow mass in a Beagle dog.

PMID- 12070822
TI  - Clinical assessment of acid-base status: comparison of the Henderson-Hasselbalch
      and strong ion approaches.
AB  - The traditional approach for clinically assessing acid-base status uses the
      Henderson-Hasselbalch equation to categorize 4 primary acid-base disturbances:
      respiratory acidosis (increased PCO2), respiratory alkalosis (decreased PCO2),
      metabolic acidosis (decreased extracellular base excess or actual HCO3-
      concentration), and metabolic alkalosis (increased extracellular base excess or
      actual HCO3- concentration). The anion gap is calculated to detect unidentified
      anions in plasma. This approach works well clinically and is recommended for use
      whenever serum total protein, albumin, and phosphate concentrations are
      approximately normal. However, because the Henderson-Hasselbalch approach is more
      descriptive than mechanistic, when these concentrations are markedly abnormal the
      Henderson-Hasselbalch equation frequently provides erroneous information as to
      the cause of an acid-base disturbance. The new quantitive physicochemical
      approach to evaluating acid-base balance uses the simplified strong ion model to
      categorize 6 primary acid-base disturbances: respiratory acidosis (increased
      PCO2), respiratory alkalosis (decreased PCO2), strong ion acidosis (decreased
      strong ion difference), strong ion alkalosis (increased strong ion difference),
      nonvolatile buffer ion acidosis (increased plasma concentrations of albumin,
      globulins, or phosphate), and nonvolatile buffer ion alkalosis (decreased plasma
      concentrations of albumin, globulins, or phosphate). The strong ion gap is
      calculated to detect unidentified anions in plasma. The simplified strong ion
      approach works well clinically and is recommended for use whenever serum total
      protein, albumin, or phosphate concentrations are markedly abnormal. The
      simplified strong ion approach is mechanistic and is therefore well suited for
      describing the cause of any acid-base disturbance.

PMID- 12070824
TI  - Validation of the Coulter AcT Diff hematology analyzer for analysis of blood of
      common domestic animals.
AB  - The objective of this study was to compare and assess the agreement between the
      Coulter AcT Diff hematology analyzer (CAD) and the Bayer Technicon H1 (H1) using
      blood samples from 391 animals of 4 species. The H1 has been used in veterinary
      laboratories for many years. Recently, Coulter modified the CAD and added
      veterinary software for hematologic analysis of feline, canine, and equine
      samples. A comparison of hemograms from dogs, cats, horses, and cattle was made
      using EDTA-anticoagulated blood samples. Both instruments were calibrated using
      human blood products. Performance characteristics were excellent for most values.
      The exceptions were MCV in canine samples (concordance correlation of.710),
      platelet counts for feline and equine samples (.258 and.740, respectively),
      feline and bovine WBC counts (.863 and.857, respectively), and bovine hemoglobin
      (.876).

PMID- 12070825
TI  - Lymph node aspirate from a 4-month-old Mastiff with weight loss, lymphadenopathy,
      and pyrexia.

PMID- 12070827
TI  - Non-albicans Candida infections in patients with hematologic malignancies.
AB  - The epidemiology of invasive Candida infections is characterized by a recent
      decline in Candida albicans and C. tropicalis with a concomitant increase in the
      incidence of non-albicans Candida species such as C. glabrata and C. krusei, a
      phenomenon at least partly ascribed to triazole use. Of particular concern is the
      recognition that these organisms are multiresistant, adding a new dimension to
      the challenge of management. C. lusitaniae, though uncommon, mainly presents as
      breakthrough fungemias in patients on antifungal therapy. C. parapsilosis, an
      organism of relatively low virulence, plays an increasing role because of its
      ability to cause intravenous line and hyperalimentation fluid colonization.
      Emergence of azole-resistant (relative or absolute) Candida species is being met
      by a new class of antifungal agents namely the echinocandins and a new generation
      of broad-spectrum triazole agents. This article addresses the biology,
      epidemiology, prognostic factors, and management of an emerging group of
      pathogens such as non-albicans Candida.

PMID- 12070828
TI  - Invasive Aspergillus infections in hematologic malignancy patients.
AB  - The incidence of invasive Aspergillus (IA) infections in patients with
      hematologic malignancies continues to increase. The most common species include
      Aspergillus fumigatus (approximately 90% of cases), A. flavus, A. niger, A.
      terreus, and A. nidulans. Most infections involve the pulmonary parenchyma,
      though systemic dissemination of the fungus from a primary pulmonary focus or the
      paranasal sinuses after hyphal invasion into blood vessels is frequent. Early
      diagnosis and initiation of appropriate antifungal therapy has been shown to
      improve the prognosis of patients afflicted with this condition. The definitive
      diagnosis of IA is based on showing the hyphal invasion in tissue specimens
      together with a positive culture for Aspergillus species from the same specimen.
      The detection of circulating fungal antigens and DNA seems to be a promising,
      rapid, and sensitive diagnostic tool for early diagnosis of aspergillosis. The
      current antifungals available for the treatment of IA include amphotericin B
      deoxycholate and lipid formulations, itraconazole and caspofungin acetate. New
      investigational antifungal drugs include the triazoles voriconazole, posaconazole
      and ravuconazole, liposomal nystatin, and 2 echinocandin derivatives
      (anidulafungin [VER-002] and micafungin [FK463]). Preventive measures include
      reduction of environmental exposure of patients from sources of infection and
      anti-fungal prophylaxis. Specialized air-handling systems capable of excluding
      Aspergillus spores, such as high-efficiency particulate air (HEPA) filtration
      with or without laminar air flow ventilation has proven to be very efficacious.
      Targeted antifungal prophylaxis for hematologic patients who are at high risk for
      developing invasive fungal infections is not currently standardized.

PMID- 12070829
TI  - Endemic mycoses in patients with hematologic malignancies.
AB  - Histoplasmosis, blastomycosis, and coccidioidomycosis are uncommon, but often
      life-threatening infections in patients who have hematologic malignancies.
      Disease occurs either as a result of new infection after an environmental
      exposure or as a result of reactivation of a remote infection. Among patients who
      have hematologic malignancies, the greatest risk appears to be in those who have
      cellular immune deficiencies. Severe pulmonary infection and widespread
      disseminated infection are the most common manifestations of these infections in
      patients with hematologic malignancies. Early diagnosis is best accomplished by
      tissue biopsy with histopathologic evaluation for the distinctive tissue forms
      characteristic of these fungi; confirmation by growth in culture is essential,
      but slow for histoplasmosis and blastomycosis. Initial treatment in the
      immunosuppressed host should almost always be with amphotericin B rather than an
      azole. Azole antifungal agents can be used in those patients who respond quickly
      to amphotericin B and for those requiring long-term suppressive therapy.

PMID- 12070830
TI  - Emerging fungal pathogens in patients with hematologic malignancies and
      marrow/stem-cell transplant recipients.
AB  - Fungal infections are a major cause of morbidity and mortality among patients
      with hematologic malignancies and recipients of bone-marrow/hematopoietic stem
      cell transplants. Although Candida and Aspergillus species remain the most common
      fungal pathogens, multiple unusual fungal pathogens are being increasingly
      recognized as a cause of infection in these patients. Many of these rare fungal
      infections have a characteristic clinical disease spectrum. Early diagnosis and
      prompt treatment of these infections is the key to a successful outcome. In this
      article, we summarize the epidemiology, pathogenesis, clinical features, and
      approach to the management of infections caused by Fusarium, Zygomycetes,
      Scedosporium, Trichosporon, Malassezia, Alternaria, Paecilomyces, and
      Penicillium.

PMID- 12070831
TI  - Pneumonia caused by herpesviruses in recipients of hematopoietic cell
      transplants.
AB  - Viral pulmonary infections are a major cause of morbidity and mortality in
      recipients of hematopoietic cell transplantation. Members of the herpesviruses
      cytomegalovirus, herpes simplex virus, varicella zoster virus, Epstein-Barr
      virus, as well as some of the more recently described herpesviruses such as HHV-6
      and HHV-8-are frequently implicated in causing pulmonary infection in this
      population. Advances in diagnostic techniques and the use of preventive or
      preemptive therapies have altered the epidemiology of infections caused by some
      of the herpesviruses; however, these viruses continue to be a significant cause
      of morbidity and mortality in hematopoietic cell transplantation. This article
      provides an overview of pulmonary herpesvirus infections that occur after
      hematopoietic cell transplantation, with an emphasis on new developments in
      epidemiology, diagnosis, prophylaxis, and treatment.

PMID- 12070832
TI  - Immune reconstitution after hematopoietic stem-cell transplantation and its
      influence on respiratory infections.
AB  - Hematopoietic stem-cell transplantation has evolved as the best therapeutic
      option for many patients with hematologic malignancy, and it is becoming more
      common as a treatment for metabolic and autoimmune disorders. The conditioning
      regimen given before transplantation virtually eliminates all pre-existing
      immunity, and the resulting immune deficits leave the host susceptible to a
      variety of respiratory infections, many of which carry significant morbidity and
      mortality. These deficits resolve over time with re-constitution of the immune
      system. However, the major arms of the immune response mature along different,
      but predictable, patterns depending on the underlying disorder, the source of
      stem cells used, and the presence of complications such as graft-versus-host
      disease. The immune deficit present at specific times posttransplant can assist
      in determining the most likely organisms to cause infection. This article
      outlines the recovery of immunity posttransplant, the most common pulmonary
      infectious complications, the noninfectious complications that mimic infection,
      and outlines appropriate preventive strategies in this group of markedly
      immunosuppressed patients.

PMID- 12070833
TI  - New antifungal agents.
AB  - Treatment of fungal infections is an area of increasing concern. This is because
      of the complexity of underlying illness in affected patients as well as the
      limited number of antifungal agents available for use. Current strategies focus
      on prevention of these infections in patients at high risk; however, this has the
      potential to lead to the emergence of clinically resistant pathogens and
      superinfections in these patient populations. Future efforts need to focus on
      earlier diagnosis and more targeted prophylaxis strategies to limit unnecessary
      use of these potentially toxic pharmaceuticals. Of equal importance is the
      development of new therapeutic options that provide viable alternatives for
      practitioners as well as optimal administration of currently available agents.
      Recent work in this area has yielded a handful of new agents that provide the
      first step in improving efficacy in these severely immunosuppressed patients, but
      outcomes still remain suboptimal for many patients suffering from severe fungal
      infections and/or serious underlying diseases. Clinical antifungal drug
      resistance must be controlled by improving a series of antifungal therapeutic
      strategies.

PMID- 12070834
TI  - Diagnostic methodologies for invasive fungal infections in hematopoietic stem
      cell transplant recipients.
AB  - Hematopoeitic stem cell transplantation (HSCT) is now a well-established
      treatment modality for a variety of solid tumors and hematologic malignancies.
      However, pulmonary complications, especially invasive fungal infections, are
      still a major cause of morbidity and mortality in this population. Successful
      management of invasive fungal infection depends on early diagnosis, prompt
      initiation of appropriate anti-fungal therapy, and return of immuno-competence.
      Appropriate timing of imaging studies and the use of invasive procedures can be
      lifesaving. Newly developed noninvasive diagnostic techniques allow for earlier
      recognition of fungal infection and hence earlier treatment. Identifying patients
      at risk for fungal infections (ie, prolonged neutropenia), and when infection is
      suspected, using appropriate diagnostic modalities, leads to effective
      prophylactic and earlier empiric therapy.

PMID- 12070835
TI  - State-of-the-art review of pulmonary fungal infections.
AB  - The endemic mycoses are restricted geographically based on environmental and
      other factors that favor the growth of these organisms in the soil.
      Histoplasmosis and blastomycosis mostly afflict patients in the Mississippi and
      Ohio River Valleys whereas coccidioidomycosis occurs primarily in the desert
      southwest United States. Cryptococcosis also may present as pulmonary disease,
      particularly in persons with cellular immune impairment. These mycoses are
      increasing in importance as causes for opportunistic disease in immunocompromised
      patients, especially those with acquired immune deficiency syndrome (AIDS).
      Aspergillus is a common cause of serious invasive fungal infection in
      granulocytopenic patients, and may cause lung infection in persons with
      preexisting pulmonary diseases or atopy. Infections with less virulent fungi,
      such as Trichosporon, Fusarium, Alternaria, Pseudallescheria, and dematiaceous
      fungi, are being recognized more frequently. The lung is the portal of entry for
      most of these pathogens, and often is prominently involved in the clinical
      syndrome. This article focuses on the recognition, diagnosis, and management of
      these important pulmonary mycoses.

PMID- 12070836
TI  - [Doppler study of gluteal arteries. A useful tool for excluding gluteal arterial
      pathology snd an important adjunct to lower limb Doppler studies].
AB  - PURPOSE: 1) To determine the negative predictive value (VPN) of duplex scan in
      patients complaining of buttock or hip pain and thereby to distinguish vascular
      claudication from other musculoskeletal or neurological diseases. 2) To show its
      complementarity in doppler investigation of lower limb arteries. MATERIALS AND
      METHODS: Prospective study by duplex scan and arteriography of 60 gluteal
      arteries in 30 consecutive patients referred to check up for lower limb
      arteriopathy or sexual impotence. Duplex scan was performed by posterior
      approach. Correlation between doppler ultrasound and arteriography was studied.
      RESULTS: The study of normal arteries was possible in all cases and only one
      normal gluteal artery could not be detected in a diabetic overweight patient. On
      60 arteries, sensitivity of duplex was 100 percent, specificity 96 percent and
      VPN 100 percent. Significant obstructive lesions were always associated with
      pathological velocimetric waveform or were not detected. CONCLUSIONS: Buttock
      claudication can appear like a typical vascular claudication or mimic
      neurological or musculoskeletal diseases. It is very useful to rule out a
      vascular causality responsible for buttock or hip pain by simple, non-invasive
      and cheap exploration. A normal doppler ultrasound of gluteal arteries can rule
      out vascular disease responsible for buttock or hip pain thereby avoiding
      arteriography. The strategy of diagnostic or therapy can be modified by such
      additional information as shown in two case reports.

PMID- 12070837
TI  - [Current aspects of cerebral protection in carotid surgery: update].
AB  - The goal of cerebral protection in carotid surgery is to reduce postoperative
      central neurological complications and thus reduce morbidity-mortality of carotid
      endarterectomy. With improving understanding of the mechanism leading to
      neurological complications, means of achieving cerebral protection have been
      developed. Preoperative evaluation of the ischemic risk is based on the
      neurological examination and on computed tomography and magnetic resonance
      imaging findings. The possibilities of arterial supply during carotid cross
      clamping can be recognized with the help of arteriography, transcranial Doppler
      or angio-MRI. Selective or systematic use of an intraluminal shunt and
      preoperative heparin therapy are the main methods used for cerebral protection.
      The risk of early postoperative stroke can also be reduced by careful
      preoperative anatomic control to detect any technical failure. Discussion on the
      usefulness of monitoring cerebral function during the procedure is closely
      related to the experience of the surgical team. The only method currently
      accepted by all surgeons is the use of stents during carotid angioplasty to
      achieve cerebral protection.

PMID- 12070838
TI  - ["Vein School." A program of education for chronic venous insufficiency patients
      at the La Lechere Hotspring].
AB  - Chronic venous insufficiency is a frequent and invalidating condition, which also
      represents an important socio-economical burden. As it is a chronic disease with
      no effective curative therapy, the preventive and educational means are of
      particular interest. The present health policy insists on the education given to
      patients suffering from chronic disease, but contrasting with other chronic
      conditions (diabetes, asthma, chronic back pain), to our knowledge, there is no
      published structured educational training programme dedicated to people suffering
      from CVI. Such an educational programme was developed at the spa resort of La
      Lechere (Savoie, France), which is specialized in the treatment of CVI. Proposed
      to voluntary patients taking the waters and driven by a multidisciplinary team
      (doctors, nurses, pharmacists), the objective was to promote a better knowledge
      in venous disease by the patients and to make them adopt a more active behaviour
      in their treatment. Three topics were approached in interactive work-groups using
      a problem solving teaching technique: "anatomy and physiology of the circulatory
      system", "venous diseases", "practical aspects life with compression stockings".
      Comparison of pre and post-teaching evaluations was performed in 149 unselected
      patients, allowing a short-term appraisal of the knowledge improvement. It showed
      a 25 to 40% increase in right answers according to the tested topic. Further
      evaluation of long term beneficial effects is needed. However, the high interest
      of patients regarding this teaching method and the content of the programme
      provides good expectations regarding a real beneficial effect on health and
      quality of life.

PMID- 12070839
TI  - [Adult Still's disease: study of a series of 11 cases].
AB  - Adult Still's disease is a systemic disease of unknown etiology. We report a
      retrospective study of 11 cases (9 females and 2 males) of adult Still's disease
      collected during 25 years. The mean age was 36 years. Fever, arthritis and skin
      rash was constant. Adenopathies and splenomegaly were observed in 2 patients. The
      laboratory findings was characterized by a constant inflammatory syndrome and
      leucocytosis. Hypertransaminasemia and hyperferritinemia were observed
      respectively in 7 cases and 3 cases. Corticosteroids were prescribed in all
      patients. Methotrexate was administered in 3 patients. Outcome was favorable in
      10 cases, death incurred in one patient, secondary to acute hepatitis.

PMID- 12070840
TI  - [Aneurysm and axillary crutches].
AB  - Axillary crutches may injure the axillary artery. A 65-year-old woman with a leg
      length discrepancy of 30 cm subsequent to childhood poliomyelitis was seen for
      subacute ischemia of the right upper limb. Axillary aneurysm with thrombosis due
      to chronic use of axillary crutches was diagnosed after clinical examinations and
      surgery. Resection-graft of the aneurysm and thrombectomy was performed and
      restored patency. Axillary crutches may cause arterial stenosis or aneurysms.
      Aneurysms may be complicated by acute thrombosis, chronic or acute distal
      embolization, or axillary mass formation. Besides not using axillary crutches,
      surgical treatment of crutch-induced axillary aneurysm must be performed before
      sometimes definitive sequelae develop.

PMID- 12070841
TI  - [Effort-induced phlebitis of the arm].

PMID- 12070842
TI  - [Cannabis-related arterial diseases].

PMID- 12070843
TI  - [Management of atherosclerotic renal artery stenoses].
AB  - Patients with atherosclerotic renal artery stenosis may develop hypertension,
      recurrent pulmonary edema and chronic renal failure, but have a much higher risk
      of dying from stroke or myocardial infarction than of progressing to end-stage
      renal disease. Indeed, atherosclerotic renal artery stenosis typically occurs in
      high risk patients with coexistent vascular disease elsewhere. Recent controlled
      trials comparing medication to revascularization have shown that only a minority
      of such patients can expect hypertension cure, whereas the results of trials
      designed to document the ability of revascularization to prevent progressive
      renal failure are not yet available. Revascularization should be undertaken in
      patients with atherosclerotic renal artery stenosis and resistant hypertension or
      heart failure, and probably in those with rapidly deteriorating renal function or
      with an increase in plasma creatinine levels during angiotensin-converting enzyme
      inhibition, especially if their renal resistance--index before revascularization
      is less than 80. With or without revascularization, medical therapy using
      antihypertensive agents, statins and aspirin is necessary in almost all cases.

PMID- 12070844
TI  - [Diagnosis and therapy of sleep disorders. Early assessment--prompt treatment].
AB  - Effective medications, as well as other effective options, are available for the
      treatment of insomnia. Since many patients do not inform their family doctors
      that they have sleep-related problems, the physician should himself question his
      patients on this point, with the aim of initiating specific treatment early
      enough to prevent such a condition becoming chronic.

PMID- 12070845
TI  - [Diagnosis and therapy of depression in general practice. The family physician is
      the primary provider].
AB  - Depression is one of the conditions with which the family doctor in particular is
      likely to be confronted. This illness which owing to the suicide risk is
      potentially fatal, is still often not recognized and consequently not treated
      appropriately. In acute and long-term treatment, considerable importance attaches
      to the prescription of a suitable antidepressant. The latest serotonin- and/or
      noradrenaline-selective antidepressants have advantages in terms of tolerability.
      The therapeutic measures with proven efficacy include cognitive-behavioral
      treatment and interpersonal psychotherapy.

PMID- 12070846
TI  - [Dementing disorders. What benefits do the new anti-dementia drugs have?].
AB  - A critical analysis of the latest studies and meta-analyses dealing with
      antidementia agents, show that the efficacy of donepezil, galantamine, ginkgo
      biloba EGb 761, memantine, rivastigmine and tacrine in Alzheimer's disease is
      adequately confirmed. With the exception of tacrine, none of these substances are
      commonly associated with severe side effects. In the case of vascular dementia,
      the efficacy of ginkgo biloba EGb 761 and memantine has been demonstrated.
      Studies on the effectiveness of the cholinesterase inhibitors for this indication
      have been initiated. Antidementia agents can delay progression of the disease by
      about 6 to 12 months. Further studies are needed to confirm evidence of a
      prophylactic effect and a synergistic action of combinations.

PMID- 12070847
TI  - [The epileptic patient in general practice. What the family physician must attend
      to].
AB  - Some 25% of patients with epilepsy are under the sole care of their family
      doctors. Treatment is applied in accordance with clear guidelines. The leading
      aim of therapy is always freedom from seizures. The gold standard is monotherapy,
      with combination treatment taking second place. In focal epilepsy, the drug of
      first choice is still carbamazepine, and in generalized epilepsy valproic acid.
      The use of the new antiepileptics should be given careful consideration, not
      least on account of their high price. Switch-over from a proprietary to a generic
      drug may be associated with the problem of differences in bioavailability.
      Routine monitoring of serum levels is not useful, but is always necessary when a
      seizure occurs unexpectedly. On account of their disease, many people with
      epilepsy are discriminated against. Questions regarding the advisability of
      having children or driving a car, should, however, not automatically elicit a
      negative response.

PMID- 12070848
TI  - [Dopaminergic agents, COMT inhibitors or amantadine? Proper treatment for your
      Parkinson patient].
AB  - Over the last six years, eight new substances for the treatment of idiopathic
      parkinsonism (IP) have been approved for use: four oral and one parenteral
      dopamine agonist (apomorphine), two COMT-inhibitors and budipine. The old drug
      amantadine has experienced a renaissance in the treatment of a complication
      occurring during long-term treatment of IP, namely levodopa-induced dyskinesia.
      Deep brain stimulation with programmable pulse generators and stereotactically
      implanted electrodes are increasingly being used in patients with severe on-off
      phases and levodopa dyskinesia. The treatment of Parkinson's disease unresponsive
      to dopaminergic substances and that associated with dementia remains
      problematical. In combinations of parkinsonism and dementia, the cholinesterase
      inhibitors are being used in particular for Lewy body dementia.

PMID- 12070849
TI  - [Managing the attacks, preventing headache. Migraine therapy in 2002].
AB  - At the heart of every migraine treatment concept is the management of the acute
      attack with effective medication. Here, the triptans have been progressively
      replacing the ergot alkaloids with their unsatisfactory relationship between
      effect and side effects. Prophylactic medication is indicated when, despite every
      non-pharmaceutic measure, migraine attacks occur on seven or more days in a
      month. The beta receptor blockers metoprolol and propranolol have so far been
      considered the substances of first choice, but in practice there is now a trend
      towards substances with a lower potential for side effects. The article provides
      an up-to-date overview of the efficacy and tolerability of the various migraine
      prophylactics.

PMID- 12070850
TI  - [Modern pain therapy in general practice. "Pain is what the patient perceives as
      pain"].
AB  - Virtually one person in two is afflicted by pain. In many cases its management,
      in particular the chronic form, is anything but appropriate to the patient's
      actual needs. Adequate pain treatment begins with the acceptance of the patient's
      perception of pain. Pain must be differentiated not only by its cause, nature and
      intensity, but also by psychosocial factors (unemployment, poverty). Within the
      framework of a comprehensive communicative interchange between physician and
      patient, self-medication and explanation models offered by the patient, must be
      considered. An important task for the general practitioner is to appreciate the
      "plastic phase" of pain, in which pain memory begins to develop, so as to
      initiate effective analgesia early on. For this purpose, it is essential that the
      physician be familiar with the interfaces with specialists, as also with the WHO
      stepped schema, in particular the indication for powerful stage III analgesics,
      and with the possible need for accompanying medication.

PMID- 12070851
TI  - [Multiple sclerosis. Therapeutic nihilism is the wrong approach here].
AB  - The standard treatment for acute multiple sclerosis relapses continues to be the
      intravenous administration of high-dose methylprednisolone. For prophylactic
      purposes, immunomodulatory therapy with interferon beta or glatiramer acetate,
      immunoglobulins or azathioprine. Studies have shown that interferon beta not only
      reduces the frequency of relapses by one-third, but also significantly delays the
      second relapse, provided it is administrated early, that is, immediately
      following the first relapse. The reduction in the patient's quality of life
      caused by the illness can be appreciably improved by a whole series of
      symptomatic treatments. The ideal situation is a cooperative effort by an
      interdisciplinary team.

PMID- 12070852
TI  - [New meta-analysis of triptanes. Concrete help, so the choice doesn't become
      overwhelming].

PMID- 12070853
TI  - [Good ruler for assessing effectiveness. Pain free with only one tablet].

PMID- 12070854
TI  - [Behavior therapy and antidepressive drugs. What helps with anxiety?].
AB  - Up to 25% of patients seen in the doctor's office are suffering from some sort of
      anxiety disorder. In accordance with the ICD-10 classification, such disorders
      include panic disorders with or without agoraphobia, generalized anxiety
      disorders, social phobia, specific phobia and mixed forms comprising anxiety and
      depression. Comorbidity with other anxiety disorders and depression is common.
      Symptoms reported by affected patients may suggest organic disease, which first
      must be excluded. All patients with severe persistent anxiety states require
      psychotherapeutic measures (cognitive behavioral treatment, exposure treatment).
      Selective serotonin reuptake inhibitors are the medication of first choice in
      anxiety disorders and comorbid depression.

PMID- 12070855
TI  - [Psychotherapy and drugs. Conquering panic].
AB  - The panic disorder with a lifetime prevalence of estimated 3.5% is an important
      psychiatric disorder of common comorbidity and long term course. The adequate
      diagnosis is rare, the common therapeutic strategies are not sufficient. Besides
      behaviour therapy the therapy with SSRIs provides a 60% remission within a few
      weeks for an uncomplicated panic disorder.

PMID- 12070856
TI  - [Pain risk factor. Preventing memory of pain].

PMID- 12070857
TI  - [Staged pain therapy plan. Opioid patch for chronic pain].

PMID- 12070858
TI  - [Better prognosis due to new treatment approaches. Therapy of schizophrenia in
      2002].
AB  - Schizophrenia is a mental illness that is often chronic and can severely
      compromise day-to-day life. In Germany, some 800,000 people--that is, almost 1%
      of the population--will suffer from schizophrenia during the course of their
      lives. In almost 50% of schizophrenics treatment is virtually exclusively in the
      hands of their family doctors. For this reason, thorough familiarity with the
      diagnosis and treatment of this condition, in particular with more recent
      therapeutic options is essential for the family doctor. Despite the fact that the
      disease often remains chronic, the prognosis has been considerably improved by
      the introduction of new therapeutic approaches.

PMID- 12070859
TI  - [Erectile dysfunction. Breaking through the silence].

PMID- 12070860
TI  - [Experiences with apomorphine SL in studies: tolerated therapy--even in problem
      patients].

PMID- 12070861
TI  - [The myocardial infarct patient. Screening for depression and treatment].

PMID- 12070862
TI  - [Long-term interferon therapy. Effectiveness in multiple sclerosis continues].

PMID- 12070863
TI  - [Atypical neuroleptics--a heterogenous group. Valuable option in acute
      psychoses].

PMID- 12070864
TI  - [Centrally acting analgesic against fibromyalgia. The body's own pain control is
      activated].

PMID- 12070865
TI  - [Multiple sclerosis. Not only gait, but thinking is also affected].

PMID- 12070866
TI  - [General practice study with atypical neuroleptics. Differences in tolerance].

PMID- 12070867
TI  - [St. John's Wort for depression. 900 mg per day should an effective dose].

PMID- 12070868
TI  - [Non-steroidal anti-inflammatory drugs with new characteristics. Rapid help in
      migraine].

PMID- 12070869
TI  - [Dopamine agonist is effective in Parkinson disease not only against tremor.
      Depression is also improved].

PMID- 12070870
TI  - [New immunomodulator for multiple sclerosis patients. 30% fewer relapse rates].

PMID- 12070871
TI  - [Controlling migraine with highly effective triptanes. Lowers rate of drug use].

PMID- 12070872
TI  - [Exercising caution in choice of psychotropic drugs. Avoid drug-induced weight
      gain].

PMID- 12070873
TI  - Stammering and therapy views of people who stammer.
AB  - This study used a postal questionnaire to seek the views of adults who stammer
      concerning the effect of stammering on their lives, the speech and language
      therapy and other remedies they have tried, and their hopes for speech and
      language therapy in the future. The 332 returned questionnaires indicated that
      stammering had the greatest adverse effect on school life and occupation. Speech
      and language therapy had been helpful to many, but the nature of the benefits and
      specific therapies used were not cited in many responses. An emergent theme in
      unhelpful therapy was the dissatisfaction that arises when individual needs are
      not met. In the future, people want help in controlling stammering and in
      developing coping strategies. The desire for timely and effective therapy for
      children, ongoing help and for group or intensive work has implications for
      service organization and therapist's skills. The survey highlights the need for
      therapists and clients to negotiate therapy aims and procedures that are clearly
      defined, appropriate to individual needs, achievable, and, if possible, recorded
      and measured. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to
      list (1) the areas most and least affected by stammering, (2) the therapy
      approaches respondents had found helpful, and (3) other remedies that tried to
      help stammering.

PMID- 12070874
TI  - A personal construct psychology view of relapse: indications for a narrative
      therapy component to stuttering treatment.
AB  - Relapse following treatment for stuttering is a common problem for many clients.
      It has often been suggested that one factor contributing to relapse is the
      client's difficulty in adjusting to a new role as a fluent speaker. In this
      tutorial article, we first present a personal construct view of relapse, which
      suggests that this difficulty may be addressed by increasing the meaningfulness
      of the fluent speaker role for the speaker. Section 3 proposes that post
      treatment success for persons who stutter may be facilitated by the use of a
      narrative approach to counseling in which the meaningfulness of the fluent
      speaker role is elaborated. In this approach, clients are guided through a
      process of deconstructing their stuttering-dominated personal narrative, followed
      by the reconstruction of an alternative narrative that is more compatible with
      being a fluent speaker. EDUCATIONAL OBJECTIVES: The reader will (1) learn about a
      personal construct psychology perspective on resistance and relapse in stuttering
      therapy, (2) be able to describe a narrative approach to counseling for people
      who stutter that is directed toward the long-term maintenance of fluent speech
      and the steps of deconstruction of the dominant stuttering narrative and
      reconstruction of a new, more fluent personal narrative, and (3) be able to
      prepare a series of narrative interview questions with which to engage clients in
      conversations that may facilitate the deconstruction and reconstruction
      processes.

PMID- 12070875
TI  - Academic and clinical education in fluency disorders: an update.
AB  - This paper presents a survey of the academic and clinical education in fluency
      disorders provided by American Speech-Language-Hearing Association (ASHA)
      accredited training programs. Respondents were 159 programs (out of 256, return
      rate = 67.4%) that completed a questionnaire seeking information about the
      courses and clinical experiences they require, the expertise of their faculty and
      supervisors, changes following the 1993 modification of training requirements for
      the ASHA certificate of clinical competence (CCC), and preliminary plans for
      changes in preparation for the 2005 standards. Results, which supplement findings
      from an earlier survey distributed in 1997 (Yaruss, 1999), indicated that nearly
      one-quarter of programs allow students to graduate without coursework in fluency
      disorders, and nearly two-thirds allow students to graduate without clinical
      practicum experiences. Findings suggest a trend toward fewer required classes
      taught by less experienced faculty, fewer clinical hours guided by less
      experienced supervisors, and a greater likelihood that students will graduate
      without any academic or clinical education in fluency disorders. Given the
      repeated finding that many speech-language pathologists are uncomfortable working
      with people who stutter, as well as ASHA's apparent de-emphasis of fluency
      disorders within the increasing scope of practice in the field of speech-language
      pathology, these results are a cause for concern about the future of fluency
      disorders. EDUCATIONAL OBJECTIVES: The reader will learn about (1) the coursework
      and clinical practicum experiences that are currently required for students in
      ASHA-accredited training programs; (2) trends indicating a reduction in training
      requirements for fluency disorders; and (3) ways of improving these requirements.

PMID- 12070876
TI  - Evaluating rate, accuracy, and fluency of young children's diadochokinetic
      productions: a preliminary investigation.
AB  - Diadochokinetic (DDK) rates are commonly assessed in children with speech
      language disorders, even though the implications of fast or slow DDK rates are
      not clear. This study explored the possibility that the accuracy and fluency of
      DDK productions may provide a meaningful supplement to traditional measures of
      DDK rate. Participants were 15 boys, age 3-7, with normal speech-language
      development, who were asked to produce "puh-tuh-kuh" or "pattycake" in a standard
      DDK task. Analyses revealed that normally developing children produce frequent
      articulation errors but few disfluencies during DDK tasks. Errors and
      disfluencies did not affect DDK rate, suggesting that the rate of DDKs may be a
      relatively insensitive measure of children's speaking abilities. Although an
      expected correlation was found between age and overall DDK rate, no correlations
      were found between age and the frequency of articulation errors or speech
      disfluencies. Findings suggest that measures of DDK accuracy and fluency may
      provide information about children's speech development that is independent of
      age and may be more closely related to oral motor development than rate. Overall,
      results underscore concerns with the interpretation of DDK rate and highlight
      ways that rate measures might be supplemented with measurement of accuracy and
      fluency in the evaluation of children's speaking abilities. EDUCATIONAL
      OBJECTIVES: The reader will learn about a technique that may facilitate the
      evaluation of young children's oral DDK abilities. The reader will learn about
      the frequency and type of errors children produce on DDKs and how this
      information can be used in the assessment of children's oral motor abilities.

PMID- 12070877
TI  - Richard R. Martin--an appreciation of his career.

PMID- 12070878
TI  - Linkage and association. The transmission/disequilibrium test for QTLs.

PMID- 12070879
TI  - Parametric linkage analysis.

PMID- 12070880
TI  - Joint linkage and segregation analysis using Markov chain Monte Carlo methods.

PMID- 12070881
TI  - Approaches to the analysis of QTL data in mice, using the nonobese diabetic mouse
      as an example.

PMID- 12070882
TI  - Experimental designs for QTL fine mapping in rodents.

PMID- 12070883
TI  - Approaches to the analysis of complex quantitative phenotypes and marker map
      construction based on the analysis of rat models of hypertension.

PMID- 12070884
TI  - A case study of QTL analysis in a mouse model of asthma.

PMID- 12070885
TI  - QTL analysis in plants.

PMID- 12070886
TI  - Association studies.

PMID- 12070887
TI  - QTL analysis in livestock.

PMID- 12070888
TI  - Nonparametric linkage analysis. I. Haseman-Elston.

PMID- 12070889
TI  - Nonparametric linkage analysis. II. Variance components.

PMID- 12070890
TI  - [Sustained development of the Mexican College of Allergy, Asthma, and Clinical
      Immunology].

PMID- 12070891
TI  - [Psychological profile of the pediatric asthma patient].
AB  - BACKGROUND: When a child develops asthma symptoms, several changes in his/her
      behavior, in his/her family and in his/her social environment begin. OBJECTIVE:
      To identify the most frequent personality traits and psychological disturbances
      in asthmatic children and adolescents. MATERIAL AND METHODS: A transversal,
      observational and descriptive study was performed on 85 asthmatic children and
      adolescents ages from 5 to 18 years old that attended a questionnaire, and a
      graphic test on 77 of those children, which consisted on drawing two pictures.
      Such pictures were analyzed by a psychotherapist to determine the personality
      traits and the psychological disturbance present in these individuals. RESULTS:
      All the children answered positively at least one of the questions which detect
      data related to depression in the questionnaire, being the more frequent: easy
      anger (40%), insomnia (29%), sadness (15%), auto-aggression or suicide ideas
      (11%) and loss of appetite (6%). According to graphic test interpretation, 39% of
      children showed a depression disturbance, 29% adaptation disturbance with
      depression symptoms, and 12% an adaptation disturbance. In addition, we found
      that 2 children were victim of abuse and negligence into their families.
      CONCLUSION: The 100% of the evaluated asthmatic children and adolescents, showed
      data related to depression presence.

PMID- 12070892
TI  - [Griscelli syndrome in a Mexican girl].
AB  - Griscelli syndrome is an infrequent disease first described in 1978. It is
      inherited in autosomal recessive form, and is distinguished by partial albinism,
      pigmentation dilution, cellular immunodeficiency, neurological involvement and
      uncontrolled phases of macrophage and lymphocyte activation. We report the case
      of a female child who started with ataxic gait when she was 23 months old. At
      physical examination a phenotype with brown skin and silvery gray hair, eyebrows
      and eyelashes was observed. Neurological evolution was with remissions and
      exacerbations, with cerebellar and, finally, bulbar compromise.

PMID- 12070893
TI  - [Fungal spores in the environment of the asthmatic patient in a semi-desert area
      of Mexico].
AB  - OBJECTIVE: To analyze the frequency and type of fungal spores in the habitat of
      sensitized asthmatic patients, its relationship with skin test reactivity to
      fungi and indoor factors favoring the fungi development. MATERIAL AND METHODS:
      Indoor airborne fungi were collected from the houses of 85 patients using fungal
      culture methods and adherent cover glasses. Data were analyzed as a cross
      sectional study. RESULTS: The prevalence of positive fungi skin test reactivity
      was 22%, the main reactivity was for Aspergillus (54%), Alternaria (51%) and
      Monilia (48%), and most frequent cultured fungi were: Cladosporium (76%),
      Alternaria (57.5%) and Aspergillus (51.3%). Another molds (Dreshlera,
      Rhodotorula) not included in the skin test reactivity panel nor immunotherapy
      plans were cultured. The fungus spores mean concentration was 1788/m3 +/- 1637
      (930 to 10,230/m3) without qualitative or quantitative differences when several
      house areas were compared. The association of skin reactivity and indoor exposure
      were significant only for Aspergillus (RR 3.14, 95% CI 1.77-5.58). The use of
      ventilation-air-conditioning systems (42%), personal humidifier or nebulizers
      (43%), dampness inside the houses were important characteristics. CONCLUSIONS:
      Indoor fungus pollution is also important in semi-desert areas, due to high
      prevalence of many factors that contribute for its development and proliferation.

PMID- 12070894
TI  - [Allergic rhinitis and ashtma: 2 illnesses. The same disease?].
AB  - Disturbances of the upper and lower airways frequently coexist, and the
      association between allergic rhinitis and asthma is an example of that. The
      relationship between allergic rhinitis and asthma probably occurs because both,
      nasal and bronchial mucosas are elements of a "united airway", and on the other
      hand, allergic rhinitis and asthma are manifestations of a common allergic
      disease. Allergic rhinitis and asthma are not only statistically associated, but
      have pathophysiological and clinical similarities. Allergic rhinitis is itself a
      risk factor for the development of asthma, but additionally may confound the
      diagnosis of asthma and may exacerbate coexisting asthma. The management of
      allergic rhinitis, mainly with the use of intranasal corticosteroids, improve
      asthma symptoms and lung function in asthmatic patients. Several mechanisms have
      been proposed to link the nose and bronchi, which include: postnasal drip of
      inflammatory cells and pro-inflammatory molecules; a possible nasobronchial
      neural reflex; an increased exposure of the lower airways to dry and cold air as
      well as aeroallergens because the mouth breathing secondary to nasal obstruction;
      and an increased susceptibility to rhinovirus infection secondary to an increased
      ICAM-1 expression in the nasal mucosa of patients with allergic rhinitis. A
      better understanding of the rhinitis-asthma relationship nature might allow the
      creation of better strategies for the integral treatment of patients with these
      diseases.

PMID- 12070895
TI  - [Errors in the technique of using measured-dose inhalers in asthmatic children
      and adolescents].
AB  - BACKGROUND: The MDI's are widely used in the treatment of asthma and are
      relatively easy to use. The response to this medicament is influenced by several
      facts that include the physical characteristics of the container and the
      technique used by the patient. OBJECTIVE: To identify the mistakes made by
      asthmatic children and teenagers in the use of the MDI's. MATERIAL AND METHODS:
      This paper was a descriptive and observational study in 57 asthmatic patients who
      were between 5 to 17 years. For the evaluation of the inhalation technique we
      used a placebo without a spacer. There are 5 steps for the correct use of the
      inhaled medications: 1) opening, 2) agitation, 3) coordination between inhalation
      and the shoot of the MDI's, 4) a deep breath and holding it for at lest 6
      seconds. RESULTS: 20 of the 57 patients (35%) followed all the steps correctly.
      The most frequent mistake was to take the deep breath, which was perform only by
      20 (35%) out of the children. The second mistake we found in this study was the
      up holding inspiration at least for 6 seconds, which was done properly only by 31
      patients (54%). CONCLUSIONS: The implantation of inhaled therapy programs
      directed and performed by specialists is recommended.

PMID- 12070896
TI  - [Microbiological monitoring of mussels and clams collected from the shellfish
      growing marine areas in Rimini Province].
AB  - A 5 years survey (1996-2000) was performed on the microbiological quality of
      shellfish (mussels and clams) collected from authorized shellfish-growing area of
      the North Adriatic Sea (province of Rimini). 7.0% of mussel samples (33/474) and
      21.9% of clam samples (218/996) exceeded the legal limits for faecal indicators
      (Dlgs 530/92). The faecal contamination of shellfish was related to the organic
      pollution arriving from inland surface waters. In fact shellfish harvested near
      the coast were more contaminated, as well as shellfish grown in the surface
      layers of the open sea, where the fresh waters of the streams tend to stratify.
      Faecal contamination was also directly correlated with rainfall, probably because
      the atmospheric precipitation, increasing the flow of the streams, favoured the
      transport of organic substances and micro-organisms deriving from the soil
      washing and the municipal sewage effluents. Furthermore, when rainfall was
      particularly plentiful, sewage inflow could also exceed the hydraulic capacity of
      the treatment plants; thus making necessary to discharge untreated waste directly
      into surface waters. Salmonellae were found in 0.7% of clam samples. Although
      this percentage is very low, it shows that pathogenic micro-organisms are present
      in this area of sea. This finding, together with the high variability of
      shellfish pollution due to occasional factors as rainfall, emphasise the
      importance of the systematic monitoring of the microbiological quality of
      shellfish.

PMID- 12070897
TI  - [Epidemiology of Cesarean section and birth surveillance].
AB  - The authors studied the incidence and the determinants of cesarean section in ASL
      Naples 4. In addition while they analysed the reliability and completeness of
      birth certificates in order to verify their accuracy for statistical and
      epidemiological purposes. The results show an increase of cesarean section higher
      than national mean (from 1997 to 2000: 44.5-54.9%), rarely justified by real risk
      conditions. 41.1% of vertex deliveries required cesarean section. The most
      frequent indications were repeated cesarean section (40.6%) and fetal problems
      (39.3%) in the multiparous; fetal dystocia (27.8%) and fetal distress (17.1%) in
      the primiparous. The quality of the compilation of the certificates was
      unsatisfactory for completeness and reliability. Indeed, 14.9% of 1997 birth
      certificates and more than 70% in the following years did not reach the
      epidemiological services of ASL; moreover, the comparison with clinical records
      proved that 46.9% of presentations resulted abnormal on clinical records were
      vertex on the birth certificates.

PMID- 12070898
TI  - [Opportunity for development of laparoscopic procedures in the hospital setting:
      costs and benefits for the surgical unit].
AB  - Physician are induced, by technical development, to demand new devices and
      instruments and to introduce new method for diagnosis and treatment. In order to
      do a right economic planning in public health, it's necessary to evaluate costs
      of technologies, because sometimes there isn't neither a right plan for
      acquisition nor an efficient control system. One the most stressed medical branch
      by innovative technologies is the surgery, in particular after the coming of
      laparoscopic surgery. The will to do, in every way laparoscopic approach, induces
      to evaluate costs of this surgery, specially cholecystectomy, that is identified
      by four specific DRGs. In this paper we compare laparotomic versus laparoscopic
      cholecystectomy in terms of costs and length of stay; the break-even analysis has
      been performed to determine the number of laparoscopic operations necessary to
      balance the costs.

PMID- 12070899
TI  - [Relationship between the university and the National Health Services: the
      experience in northern Italy].
AB  - The paper summarises the results of the experiences presented at the "Meeting on
      Public Health in Northern Regions" held in Milan. Despite the differences seen at
      local level the importance of interaction between "academic" expertise and field
      attachment is seen as crucial. Actual legislation pushes toward considering the
      academic role as a result of the development of teaching, research, health care
      skills. The paper consider that also a public health doctor in practising should
      see his role as the result of a mix of "health care, research and teaching"
      abilities so that a harmonisation looks possible in so far as they know each
      other and work for the same objectives although in a different context. On the
      other hand, the University should perceive itself as service given to a
      community. So, in conclusion, if politics means the common interest in the public
      affairs this fourth dimension should join the three considered above in general
      terms and particularly in the field of Public Health Medicine.

PMID- 12070900
TI  - [Social and health services needs in a sample of elderly people in Catanzaro].
AB  - The aim of this study is to analyze the general health state conditions of older
      people living in Catanzaro, using a multidimensional assessment instrument to
      determine their social and health needs. To this purpose, a sample of 544
      individuals (344 women and 210 men) older than 65 years of age (mean age = 75.3)
      was selected from the general population. All subjects were administered the OARS
      (Older Americans Resources and Services) questionnaire that evaluates five areas:
      physical health, mental health, social resources, economic resources and
      Activities of Daily Living (ADL). The percentage of subjects with score 3 or more
      in each area, and therefore identified as partially or totally dependent, is
      higher in the area of physical health (17.9%) and ADL (16.6%). About 65% of the
      sample is not disabled in any of the different areas, while 8% is dependent in 3
      or more areas. These subjects are partially or totally dependent elderly people,
      who stay at their own house in precarious conditions, and are able to remain
      there only because they are helped by informal caregivers. Probably these people
      are those for whom any domiciliary help is necessary and more urgent in order to
      support the existing stability and to avoid institutionalization.

PMID- 12070901
TI  - [Sexually transmitted diseases: epidemiological and social aspects].
AB  - STDs represent a major public health problem for two reasons: their serious
      sequelae and the facts that they facilitate transmission of HIV. This article
      presents WHO estimates new cases of some of curable STDs, and italian data from
      national reporting system (published from ISTAT and ISS). The number of new
      reported cases decreases in Italy, but reported cases are not all cases. People
      with STDs tend not to seek treatment or to self-medicate, this behaviour is
      common in youths. In many cases STDs are asymptomatic in both sexes, particularly
      in women. Women are also much more vulnerable biologically, culturally,
      socioeconomically. There is also a lack of notification by physicians. Important
      social determinants of STDs diffusion are migration and travels. Prevention and
      control of STDs need collaboration between medical disciplines: gynaecology,
      urology, dermo-venerology, microbiology, epidemiology, public health.
      Contributions of nurses, laboratory technician and social workers are also
      required. The role of public health specialists in the prevention is strictly
      related to health education. Health education will promote responsible sexual
      behaviour and early recourse to health services by people with STDs and their
      sexual partners.

PMID- 12070902
TI  - [Tobacco habits in a cohort of 4,135 adolescents attending high school in
      northern Italy. Results of a multicenter study].
AB  - Assuming that adolescence--a high risk age as far as this behavior is concerned-
      is the crucial stage for prevention procedures, we don't know much about Italian
      adolescents' tobacco related behaviors, regardless of the fact that tobacco
      smoking is one of the most relevant problems of Public Health. The goal of this
      research has been assessing, through a multicentric study using an anonymous
      questionnaire, how spread is this behavior among 4135 students attending high
      school in five different areas of Northern Italy. The research points out a
      remarkable spreading of the phenomenon and suggests to anticipate prevention
      procedures during compulsory education, taking in account gender features.

PMID- 12070903
TI  - [Epidemiology of accidents related to sea-swimming in the Tuscany Region using a
      health-promotion strategy. Preliminary report].
AB  - In the summer season 1999 an integrated epidemiological surveillance system
      (involving mobile emergency medical services, first aid and tourist stations,
      hyperbaric medical centres, bathing attendants) of sea-bathing-related accidents
      was set up on the coasts of Tuscany, central Italy, aimed at health promotion and
      education. The pilot phase allowed to collect a first set of information on
      periods and time with highest incidence of events, type of assistance delivered,
      kind of accident (trauma or illness) and seriousness of the event as codified by
      emergency medical services. The pilot experience also pointed out the changes to
      detection tools needed in order to obtain more precise and comparable data. Such
      corrections, introduced during the summer season 2000, could contribute to the
      creation of a model with potential applications in other Italian and European
      coastal regions.

PMID- 12070905
TI  - Antifungal effect of Australian tea tree oil on Malassezia pachydermatis isolated
      from canines suffering from cutaneous skin disease.
AB  - The lipophilic yeast Malassezia pachydermatis is part of the normal skin flora of
      most warm-blooded organisms. In a number of surveys it could be demonstrated that
      this yeast species might be involved in different skin diseases like seborrhoeic
      dermatitis, especially in dogs and cats. In order to look for an alternative
      therapeutic agent to the commonly used antimycotic and antiseptic synthetic
      substances the in vitro activity of Australian tea tree oil, the essential oil of
      Melaleuca alternifolia, against several strains of Malassezia pachydermatis was
      examined. All tested strains showed remarkably high susceptibility to tea tree
      oil. With these results the excellent antibacterial activity of tea tree oil is
      extended to a new group of fungal pathogens colonizing mainly mammals' skin.
      During the last ten years there was an increasing popularity of tea tree oil
      containing human health care products. The presented data open up new horizons
      for this essential oil as a promising alternative agent for topical use in
      veterinary medicine as well.

PMID- 12070904
TI  - [Survey of the presence of bacterial pathogens in foods sold at retail stores in
      the city of Cassino].
AB  - The presence of bacterial food pathogens was evaluated in 154 food samples
      collected from supermarkets and butchers in the city of Cassino (South-Central
      Italy). Food pathogens were identified in 17.5% of the total food samples. In the
      raw meat samples, 24.6% tested positives for Listeria monocytogenes, 4.3% for
      Salmonella and 2.9% for Escherichia coli O157. Y. enterocolitica, only
      investigated in pork meat, was identified in 7.4% of the samples. In poultry, L.
      monocytogenes was identified in 55% of the samples.

PMID- 12070907
TI  - [Unilateral laparoscopic cryptorchidectomy in a llama].
AB  - Cryptorchism is an inherited congenital abnormality characterized by the failure
      of one or both testes to descend into the scrotum. Diagnosis can be difficult if
      the retained testicular tissue cannot be localized during clinical examination
      and the history of the animal is unknown, or if the animal shows persistent male
      behaviour despite the history of successful previous castration. The present case
      report describes the history of a cryptorchid Lama and the techniques of general
      anesthesia and laparoscopic cryptorchidectomy advocated.

PMID- 12070906
TI  - Phytotherapy of chronic dermatitis and pruritus of dogs with a topical
      preparation containing tea tree oil (Bogaskin).
AB  - Localised dermatitis, for example unspecific eczema or skinfold pyoderma, is a
      very common diagnosis in dogs. Typical and impressive complaints are pruritus,
      erythema, erosion and oozing surface. With respect to the underlying disease
      dermatological treatment is indicated, usually based on antimicrobial and
      antipruriginous active substances, it can include transient glucocorticoids. An
      effective and safe alternative might be a phytotherapeutic topical preparation
      containing tea tree oil. Tea tree oil exerts both antimicrobial and
      antipruriginous effects. In an open multicenter study efficacy and safety of a
      standardized 10% tea tree oil cream applied thinly and twice daily for 4 weeks
      was tested in 53 dogs with chronic dermatitis, particularly non-specific eczema,
      allergic dermatitis, interdigital pyoderma, acral lick dermatitis and skinfold
      pyoderma. Analysis of efficacy assessed by investigating veterinarians showed a
      good or very good response to treatment for 82% of the dogs, significant at a 5%
      level (p = 0.05). At the end of the study a strong and significant reduction (p =
      0.001) as well as disappearance of major symptoms were observed. Only two adverse
      events (local reactions) possibly related to tea tree oil occurred during
      therapy. Consequently the tested study medication (Bogaskin) can be considered an
      alternative for uncomplicated and localised dermatitis in dogs. Bogaskin might
      allow reduction of other pharmaceutical products, perhaps even replace standard
      therapy.

PMID- 12070908
TI  - [Cardiac hemangiosarcoma in a dog].
AB  - The case of a 11 year-old mix breed dog is being described. It initially
      presented for watery diarrhea and inappetence. During the diagnostic workup, the
      dog developed a sustained ventricular tachycardia. Echocardiography showed a mass
      extending from the wall of the right ventricle which filled up the ventricle
      almost completely. Histopathologic examination of the mass after euthanasia of
      the dog revealed a hemangiosarcoma.

PMID- 12070909
TI  - [Development of ideas about nervous system signaling for the last quarter of the
      century].

PMID- 12070910
TI  - [Associated with DNA polymerases and autonomic 3'-5'-exonucleases from
      invertebrates, protozoa and bacteria].

PMID- 12070911
TI  - [The influence of population factors on phospholipid content of different tissues
      in lemmings Microtus oeconomus in their natural habitat].

PMID- 12070912
TI  - [Regulation of functional activity of adenylate cyclase signal system by
      synthetic spiral peptides in cultured fibroblasts of mice strain L (subspecies
      LSM)].

PMID- 12070913
TI  - [Changes in the spectrum of digestive proteases in rat postnatal development ].

PMID- 12070914
TI  - [Membrane and soluble isoforms of intestinal ferments of young rats, whose
      mothers were on low protein diet during pregnancy and lactation].

PMID- 12070916
TI  - [NO-dependent glutamate regulation of serotoninergic system activity of grape
      snail Helix lucorum].

PMID- 12070915
TI  - [Influence of malnutrition during lactation on biochemical blood parameters of
      Greenland seal Phoca groenlandica pups].

PMID- 12070918
TI  - [Influence of thyroid hormones on memory imprinting of chemical signals in early
      development of sturgeon Acipenser gueldenstaedti].

PMID- 12070917
TI  - [The role of non-NMDA receptors in the associative learning process of the
      honeybee Apis mellifera].

PMID- 12070919
TI  - [The study of cardiotonic action of green frog poison Bufo viridis].

PMID- 12070920
TI  - [Morphologic-functional characteristics of neurosecretory cells from preoptic
      nucleus of frog Rana temporaria after hypophysectomy and vasotocin injections].

PMID- 12070921
TI  - [The influence of avoidable and unavoidable stress on the level of catecholamines
      in adrenal glands and corticosterone in the plasma in young and old rats].

PMID- 12070922
TI  - [The influence of modulators on the membrane digestion process in Siberian
      sturgeon Acipenser baeri].

PMID- 12070923
TI  - [Glycogen phosphorylase activation by glycogen phosphorylase kinases: dependence
      on ATP concentration and species specificity of enzymes].

PMID- 12070924
TI  - [The role of nitric oxide in rat postnatal resistance to neurotoxic action of
      hyperbaric oxygen].

PMID- 12070925
TI  - [Treatment protocol for cervical carcinoma].
AB  - INTRODUCTION: Cervical cancer is the second most common cancer in women worldwide
      and the second cause of cancer death among women. About 95% (90% in developed
      countries) of invasive carcinomas are of squamous types, and 5% (10% in developed
      countries) are adenocarcinomas. FIGO classification of cervical carcinomas, based
      on clinical staging and prognostic factor dictate therapeutic procedures and help
      in designing treatment protocols. THERAPEUTIC MODALITIES: Surgical therapy
      includes conization, radical hysterectomy with pelvic lymphadenectomy and
      palliative operation--urinary diversion and colostomy. Radiotherapy,
      brachytherapy and teletherapy are most recently combined with chemotherapy as
      concurrent chemoradiation. DISCUSSION AND CONCLUSION: No change in therapeutic
      modalities will ever decrease mortality rate of cervical carcinoma as much as
      education, prevention and early screening. The 5-year survival for locally
      advanced disease has not improved during the last 40 years as a result of failure
      to deliver therapy to the paraaortic region. Paraaortic lymph nodes should be
      evaluated before therapy planning by different imaging procedures, or more
      exactly by surgical staging: laparoscopy or laparotomy. Radical operations of
      cervical carcinoma should be performed by experienced surgeons, educated for this
      type of operation, with sufficient number of cases.

PMID- 12070926
TI  - [Topical agents used in the treatment of burns].
AB  - INTRODUCTION: Understanding of fluid shifts and recognition of the importance of
      early and appropriate fluid replacement therapy have significantly reduced
      mortality in the early postburn period. After the burn patient successfully
      passes the resuscitation period, the burn wound represents the greatest threat to
      survival. HISTORY: Since the dawn of civilization, man has been trying to find an
      agent which would help burn wounds heal, and at the same time, not harm general
      condition of the injured. It was not until the XX century, after the discovery of
      antibiotics, when this condition was fulfilled. In 1968, combining silver and
      sulfadiazine, Fox made silver-sulphadiazine, which is a 1% hydrosoluble cream and
      a superior agent in topical treatment of burns today. CURRENT TOPICAL AGENTS:
      None of the topical antimicrobial agents available today, alone or combined, have
      the characteristics of ideal prophylactic agents, but they eliminate colonization
      of burn wound, and invasive infections are infrequent. With an excellent spectrum
      of activity, low toxicity, and ease of application with minimal pain, silver
      sulfadiazine is still the most frequently used topical agent. CONCLUSION: The
      incidence of invasive infections and overall mortality have been significantly
      reduced after introduction of topical burn wound antimicrobial agents into
      practice. In most burn patients the drug of choice for prophylaxis is silver
      sulfadiazine. Other agents may be useful in certain clinical situations.

PMID- 12070927
TI  - [Anthrax--the past, present and future].
AB  - HISTORY: Anthrax has been known since ancient times. Besides some references in
      the Old Testament, there is evidence of plagues in ancient Egypt, as well as
      descriptions of the disease by the Roman poet Virgil. ETIOLOGY: Anthrax is caused
      by Bacillus anthracis, unmovable, aerobic, gram-positive rods. It forms spores,
      which can survive for years in the environment. PATHOGENESIS: Capsular
      polypeptide and anthrax toxin are the principal virulence factors of Bacillus
      anthracis. Anthrax toxin consists of three proteins called protective antigen,
      edema factor, and lethal factor. It is thought that the inflammatory mediator-
      lethal factor is stored within the macrophage during the early stage of
      infection. It is rapidly released in large amounts into the blood stream and once
      the threshold for lysis is reached, it may be the cause of sudden death.
      EPIDEMIOLOGY: Grass-eating animals are usually infected by the bacilli from grass
      and ground. The disease is transmitted to people by contact with the sick animals
      or their products, such as wool, skin, meat etc. CLINICAL FEATURES: Two clinical
      forms exist: outer--cutaneous and inner, including inhalation and
      gastrointestinal anthrax. While cutaneous anthrax is easily cured, the inner
      forms have high mortality rates. DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS: The
      diagnosis is easily established in cutaneous cases, characterized by black
      eschar. Severe intoxication and collapse during the course of bronchopneumonia or
      hemorrhagic enteritis should arise suspicion of anthrax. THERAPY: Hospitalization
      of patients is mandatory. Bacillus anthracis is susceptible to a number of
      antibiotics, including penicillin, erythromycin, tetracyclines, cephalosporins
      etc. PREVENTION: General veterinary prevention including vaccination of livestock
      and control of products is very important. The vaccine consists of anthrax
      bacillus that is attenuated. The endangered population, such as animal workers
      and military personnel should be vaccinated. Annual schedule of booster
      immunization must be maintained. ANTHRAX AS A BIOLOGICAL WEAPON: Anthrax has been
      developed as a weapon of mass destruction since World War I. During accidental
      release from a biological warfare factory in the former Soviet Union, 68 people
      died. The ease of laboratory production and its dissemination via aerosol led to
      its adoption by terrorists, as shown by recent happenings in the USA. CONCLUSION:
      A good knowledge of anthrax, its transmission and potentials as a biological
      weapon is essential for timely prevention and protection.

PMID- 12070928
TI  - [Endometriosis and infertility].
AB  - INTRODUCTION: Endometriosis is frequent in infertile women, but the relation
      between these two conditions has still remained unclear. Our intention was to
      present the pathogenesis of endometriosis, mechanism of the associated
      infertility and a rational approach to treatment of this frequent medical
      problem. PATHOGENESIS OF ENDOMETRIOSIS: The peritoneal form is most probably
      generated by implantation of the endometrium by menstrual reflux. Endometriomas
      are most probably formed by invagination and metaplasia of the ovarian
      mesothelium or by metaplasia of the epithelium of inclusion cysts. Adenomyosis of
      the rectovaginal septum develops from embryonic remnants of the Mullerian ducts.
      DIAGNOSIS: Laparoscopy is a method of choice which provides safe diagnosis,
      estimation of the disease and is an optimal method of treatment. PATHOGENESIS AND
      THERAPY OF INFERTILITY: The relation between mild forms of disease (Stage I and
      II) and infertility has remained unclear. Surgical removal of ectopic foci does
      not affect female fertility. The expectant treatment during one to four years has
      been followed by pregnancy in 50% of patients. In patients with III and IV stage
      disease, there is a frequent mechanical cause of infertility. Expectant treatment
      was followed by 25% incidence of pregnancy in patients with stage III disease and
      0% in patients with stage IV endometriosis. Surgical reconstruction of normal
      anatomical relations resulted in pregnancy in 40-60% of patients. Administration
      of any drug therapy, either single or combined with surgical treatment does not
      increase the fertility rate. Methods of assisted reproduction are alternative
      approaches to treatment and they have to be administered after unsuccessful
      surgical treatment. Pretreatment with GnRH agonists increases the efficacy of in
      vitro fertilization.

PMID- 12070929
TI  - [Wall tension or stress in ischemic heart disease].
AB  - INTRODUCTION: Wall stress or wall tension is a conception derived from physics
      (Laplace's law) and represents the systolic force or work per surface unit. It is
      the systolic force made by myocardial tissues. Stress increase indicates
      enlargement of the left ventricle or increase of intracavitary pressure. MATERIAL
      AND METHODS: This investigation included 170 subjects; control group consisted of
      50 patients (pts) with normal coronary angiographic finding without valvular
      anomalies and the examination group included 120 pts with coronary disease.
      Transthoracic echocardiography was performed in the left lateral position using
      computerized Hewlett Packard SONOS 1000 apparatus. Invasive hemodynamic procedure
      was performed using GENERAL ELETRICS CGR 300. Meridional and equatorial systolic
      and diastolic stress were calculated according to Grossman formula. RESULTS: The
      meridional end-diastolic equatorial stress was 18.55 +/- 12.12 dyn/cm2 x 10(3) in
      the control group, while in coronary patients it was 28.15 +/- 13.42 dyn/cm2 x
      10(3). In healthy persons the meridional end-systolic stress established by
      echocardiography was 190.37 +/- 23.15 dyn/cm2 x 10(3), while in coronary patients
      203.82 +/- 17.88 dyn/cm2 x 10(3). End-diastolic equatorial stress was 34.32 +/-
      17.18 dyn/cm2 x 10(3) in the control group and 46.13 +/- 17.82 dyn/cm2 x 10(3) in
      coronary patients. Systolic equatorial stress in the control group was 357.42 +/-
      32.15 dyn/cm2 x 10(3) and in coronary patients 385.34 +/- 35.72 dyn/cm2 x 10(3).
      The same parameters determined by invasive hemodynamic procedure were slightly
      higher, but without statistical significance in relation to the values determined
      by echocardiography (P > 0.05). CONCLUSION: Values of equatorial and particularly
      meridional stress were higher in coronary patients in relations to healthy
      persons, but without significant difference. The correlation coefficients of all
      investigated parameters established by noninvasive 2D echocardiography and
      invasive hemodynamic procedure were in one domain of medium high and high values.
      Meridional stress increases in coronary patients, equatorial in hypertensive
      patients or valvular anomalies with severe myocardial hypertrophy. In regard to
      high correlation between these two techniques, echocardiography may be considered
      a highly reliable method in evaluation of wall tension.

PMID- 12070930
TI  - Concentrating ability of the kidneys in proteinuric patients.
AB  - Proteinuria causes damage to renal tubulointerstitum. The study included 50
      patients (24 males and 26 females), mean age 46.50 +/- 13.08 years, with average
      endogenous creatinine clearance 87.29 +/- 31.17 ml/min. Regarding level of
      glomerular proteinuria patients were divided into three groups. The first group,
      with proteinuria less than 0.3 g/24 h, included 19 patients (7 male and 12
      female), average age 45.12 +/- 13.28 years and mean clearance of endogenous
      creatinine 94.27 +/- 34.70 ml/min. The second group, with proteinuria between 0.3
      and 3.0 g/24 h, comprised 18 patients (8 male and 10 female), mean age 45.39 +/-
      12.64 years, and with mean clearance of endogenous creatinine 90.07 +/- 31.89
      ml/min. The third group consisted of 13 patients (9 male and 4 female) with
      proteinuria values higher than 3.0 g/24 h, average age 50.08 +/- 13.73 years and
      mean endogenous creatinine clearance 73.25 +/- 20.44 ml/min. In order to assess
      the concentrating ability of the kidneys we investigated: urine osmolality,
      osmolar concentration index, fractional osmolar excretion, fractional urea
      excretion and free water clearance. Results were statistically analyzed using
      Student t test, Mann-Whitney U test and chi 2 test. Proteinuria leads to
      deterioration of concentrating ability of the kidneys.

PMID- 12070931
TI  - [Acute cholecystitis--early or delayed cholecystectomy].
AB  - INTRODUCTION: In our population biliary tract diseases are the most frequent
      surgical entity. If the diagnosis of acute cholecystitis is relatively clear and
      the time from onset of the disease does not exceed 72 hours, early
      cholecystectomy is recommended. The aim of this prospective study was to use
      certain analytical procedures in order to compare early and late results of early
      and delayed cholecystectomy. MATERIAL AND METHODS: 240 patients were divided into
      two groups: Group I: patients treated by early cholecystectomy and Group II:
      patients treated by delayed cholecystectomy. We compared the following:
      intraoperative findings, postoperative morbidity and mortality, complications,
      average number of patient-days and histopathological changes. RESULTS: During the
      investigated period (1998-1999), 599 (35.95%) patients with acute and 1.067
      (64.05%) patients with chronic cholecystitis were treated at the Clinic of
      Abdominal and Endocrine Surgery of the Clinical Center Novi Sad. Out of 599
      patients with acute cholecystitis, 489 (81.63%) patients underwent surgery,
      whereas 110 (18.37%) were treated conservatively. In regard to chronic
      cholecystitis, 963 (90.25%) patients were surgically treated, and 104 (9.75%)
      patients were conservatively treated. All patients from Group I were operated
      within 24-48 hours from onset of the disease or during 24 hours of
      hospitalization. They were hospitalized due to signs of cholecystitis for the
      first time, whereas this was the second hospitalization for all patients from
      Group II, 42 +/- 2.3 days after first hospitalization on average. Regarding sick
      leave in Group I patients it was calculated as follows: hospital days + home
      treatment and it made 32 +/- 3.7 days. In Group II it was calculated as follows:
      first hospitalization + home treatment + second hospitalization + home treatment
      making 53 +/- 6.7 days. CONCLUSIONS: The number and type of early and late
      complications in Group II patients justifies early cholecystectomy; in acute
      cholecystitis, cholecystectomy should be performed within 24-48 hours from the
      onset of the disease; in regard to late, early cholecystectomies are
      characterized by significantly shorter period of recovery and sick leave.

PMID- 12070932
TI  - [Osteosynthesis with Kirschner wires in the treatment of dislocation fractures of
      the forearm in children].
AB  - INTRODUCTION: Forearm fractures make 13-18% of all injuries of the upper
      extremities in children. Most of them are older than 6 years. The degree of
      tolerance is different but children younger than 8 years can tolerate 15-20
      degrees of angulation, 45 degrees of inadequate rotation and total displacement.
      Older children can tolerate angulation of 10 degrees, 30 degrees of inadequate
      rotation and complete dislocation. MATERIAL AND METHODS: Over a period of five
      years (1995-2000) 54 children with forearm fractures (22 stable and 32 unstable
      fractures) were treated at the Pediatric Surgery Clinic in Novi Sad. Closed
      reduction and percutaneous pinning were treatments of choice in 19 patients with
      unstable fractures: 7 kids with only radius pinning, three kids with isolated
      ulnar fixation, 9 kids with pinning of both bones. Open reposition and fixation
      with Kirschner wires was done in 13 kids. RESULTS: In the group of 22 children
      with stable fractures results were excellent in 17 (77%), good in 4 (18.5%), and
      satisfactory in one child (4.5%). In the group of 32 children with unstable
      fractures excellent results were noted in 24 (75%), good in 4 (12.5%),
      satisfactory in 3 (9.4%) and unsatisfactory in one child (3.1%). DISCUSSION: A
      large number of forearm fractures in children can be treated with manual
      reduction and plaster immobilisation into a tolerable position. However, in
      unstable fractures the method of choice is manual reduction with percutaneous
      pinning. Some authors prefer fixation of both bones, others fix only one.
      CONCLUSIONS: Based on our experience it is concluded that orthopedic reposition
      and percutaneous pinning of unstable forearm fractures in children is very easy
      to perform, duration of intramedullar fixation is relatively short, removal of
      pins is also very easy without anesthesia and it requires short period of plaster
      immobilisation. This provides faster rehabilitation and improves quality of life.

PMID- 12070933
TI  - [Chlamydia trachomatis--a possible cause of premature labor].
AB  - INTRODUCTION: The aim of this study was to investigate the incidence of
      urogenital infection with Chlamydia trachomatis in patients with preterm delivery
      in relation to those with term delivery. MATERIAL AND METHODS: The investigation
      included a random sample of 116 parturients. Direct immunofluorescence (DIF) test
      was used to diagnose Chlamydia trachomatis. RESULTS: In the investigated group (N
      = 53), positive finding of Chlamydia trachomatis in the urogenital tract was
      established in 6 (11.32%) patients in cervix and in 5 (9.43%) patients in the
      urethra, whereas in the control group there were 3 (4.76%) positive findings in
      the cervix and 1 (1.59%) in the urethra. The control group included patients with
      term delivery (N = 63). DISCUSSION AND CONCLUSION: Results of investigation point
      to the necessity of diagnostics and treatment of Chlamydia trachomatis in
      prevention of preterm delivery, particularly in women with previous unsuccessful
      pregnancies.

PMID- 12070934
TI  - [Treatment of pulmonary embolism and prevention of recurrence by placement of a
      vena cava filter in deep venous thrombosis: case report].
AB  - INTRODUCTION: In patients with pulmonary thromboembolism it is crucial to suspect
      the disease, establish the diagnosis and initiate anticoagulation treatment as
      early as possible in order to prevent relapses, which may be fatal. Deep venous
      thrombosis of lower extremities is the most common site of origin, which
      initially may remain obscure. CASE REPORT: Two weeks prior to admission the
      patient had right-sided chest pain accompanied with dyspnea, interpreted and
      treated as pleuropneumonia. Pulmonary thromboembolism was suspected due to
      clinical symptoms, chest X-ray, elevated enzyme levels findings, blood gas
      analysis with hypoxemia and ECG with right heart overload. The diagnosis of
      pulmonary thromboembolism confirmed by lung scintigraphy presented with perfusion
      defects. After twenty days of heparin therapy, the patient developed left leg
      edema. Ultrasound screening confirmed bilateral iliacfemoral popliteal vein
      thrombosis of iliacofemoropopliteal veins bilaterally. Phlebography performed via
      jugular vein disclosed thrombotic material in the right common iliac vein, as
      well as in the vena cava inferior. In the course of the procedure vena cava
      filter has been placed. DISCUSSION: Although the patient was receiving
      anticoagulation heparin therapy, he developed pulmonary thromboembolism relapse
      and deep venous thrombosis. In our patient, vena cava filter placement was aimed
      at preventing pulmonary thromboembolism relapse. Since a deficit of S protein was
      also established, the patient is unfortunately likely to develop thrombosis at
      other sites as well. CONCLUSION: In our patient pulmonary thromboembolism was a
      consequence of deep venous thrombosis, and the diagnosis was established by
      ultrasound screening of the lower extremities and confirmed by phlebography.
      During phlebography vena cava filter was placed in order to prevent pulmonary
      thromboembolism.

PMID- 12070936
TI  - [Hypertriglyceridemia and the atherogenic lipoprotein phenotype (triglycerides
      and atherosclerosis)].

PMID- 12070935
TI  - [20 years' of the Psychiatric Section of the Serbian Medical Society-Society of
      Physicians of Vojvodina (1982-2001)].
AB  - INTRODUCTION: Psychiatry Section of the Society of Physicians of Vojvodina (SPV)
      was founded in 1982, after the Neuropsychiatry Section of SPV was divided into
      Neurology Section and Psychiatry Section. Since then, it has a presidency, a
      president and a secretary appointed by its assembly for a two-year period.
      FOUNDATION: In the first part of the paper authors described the period when the
      Section was founded, places where its main office was, its meetings, topics and
      lecturers as well as activities of Psychiatry Section members during the
      abovementioned period. MEMBERSHIP: The second part of the paper deals with
      personal, professional and academic biographies of all former presidents of the
      Section. The first president of Psychiatry Section was Prof. Dr. Stojan Vuckovic
      and from 1982 to 1984 its office was in Novi Sad, whereas from 1984-1986 it was
      in Sombor with Dr. Stevan M. Cicovacki as president and Dr. Panta Lazic as
      secretary. From 1986-1988 the Section's office was moved from Sombor to Subotica.
      Its president was Dr. Pal Ungar and Dr. Istvan Sic the secretary. From 1988-1990
      the Section's office was moved to Senta. The new president was Dr. Milorad
      Curcic, and Dr. Katalin Kis-Kovac the secretary. In 1990 Sombor was again
      appointed to be the seat of the Section, and Dr. Ljiljana Ril was its president
      till 1992 with Dr. Sasa Mesterovic as secretary. In May 1992, the main office was
      moved to Vrsac and stayed there till 2000. The Section's president was Dr. Milan
      Beslin, and Dr. Ljiljana Mihajlovski the secretary. Senta was again appointed to
      be the seat of Psychiatry Section in 2000, with Dr. Milorad Curcic as its
      president and Dr. Josip Dadasovic as secretary. At the election assembly of the
      Psychiatry Section held on October 25, 2001 in Kikinda, presidential and
      secretarial mandates were prolonged, so the seat of the Section stays in Senta
      for the next two years. Apart from biographies, this paper also contains photos
      of all presidents of the Section.

PMID- 12070937
TI  - Antiphospholipid syndrome accompanying systemic lupus erythematosus.
AB  - The aim of the study was the assessment of the prevalence of antiphospholipid
      syndrome (APS) in patients with systemic lupus erythematosus (SLE). 72 patients
      with SLE had been investigated, 66 females and six males, aged 17 to 70 years,
      average 37.03. The presence of APA was determined using both ELISA assay for
      antiphospholipid antibodies, ASSERACHROM APA by Diagnostica Stago and clotting
      tests for lupus anticoagulant: activated partial thromboplastin time (aPTT),
      tissue thromboplastin inhibition test (TTI) and dilute Russell viper venom time
      (dRVVT). Antiphospholipid antibodies have been found in 24 patients (33.44%), 10
      of them were with positive lupus anticoagulant tests, 6 of them were with
      positive ELISA test, while 8 of them had positive coagulation and immunological
      tests. Clinical manifestations that could be related to antiphospholipid syndrome
      were present in 22 patients (30.5%). The most common were thrombotic
      complications in 16 patients (22.25), recurrent spontaneous abortions in 7
      patients (9.7%) and thrombocytopenia in 1 patient (1.39%). Presence of
      antiphospholipid syndrome was determined in 15 patients (20.83%). We can conclude
      that there is a significant correlation between presence of antiphospholipid
      antibodies and both thrombotic events and recurrent spontaneous abortions in SLE
      patients. Occurrence of thrombotic complications is in direct correlation with
      the level of antiphospholipid antibodies.

PMID- 12070938
TI  - [A sense of responsibility in health personnel as a cause of work-related
      stress].
AB  - INTRODUCTION: Job stress is a great problem in developed countries of the world,
      but in Yugoslavia, it is increased due to additional reasons associated with
      economic crisis in the society. Health services and health workers are in
      particularly difficult conditions. The aim of this paper was to examine sources
      and causes of job stress in health workers. MATERIAL AND METHODS: The research
      was undertaken among health workers treated at Health Centre "Hospital" in Novi
      Sad. The study group included health workers--doctors, nurses and laboratory
      workers, and the control group included the rest of non-medical staff. Adapted
      Siegrist questionnaire was used. Three factors were examined: extrinsic efforts
      (disturbances at work, sense of great job responsibility and the need for
      overtime work); intrinsinc efforts (major criticism, thinking about the job from
      the early morning, getting nervous because of minor problems, discontentment
      because of unsolved problems at work, relaxation at home and so on), and low
      reward (respect from the superiors and colleagues, support and security at
      workplace). Answers were scored indicating intensity (high, moderate, low, not at
      all). Statistic analysis included testing the level of significance in health
      workers in relation to non-medical staff (t test and Fisher's exact test).
      RESULTS: Applying the scoring system it has been established that health workers
      are exposed to greater job stress, great sense of very high job responsibility
      and frequent overtime work (p < 0.001) than the control group. In regard to
      answers from the second group--intrinsic effort and low reward, there was no
      statistiscal significance between the study and control group. Generally, high
      level of risk factors was established, especially presence of one or more risk
      factors. DISCUSSION: Job stress increases absenteeism, reduces work productivity,
      causes higher expenses of medical treatment, rehabilitation and staff retraining.
      It is of great importance to identify factors which cause job dissatisfaction in
      order to decrease them to the lowest level. CONCLUSION: High sense of
      responsibility in health workers is a course of job stress.

PMID- 12070939
TI  - [Molecular evidence of regression in evolution of metazoa].
AB  - Molecular data permit to construct phylogenetic trees independently of
      morphological characters. It allows to consider their evolution without the
      frames of a priori hypothesis of regularities of morphological evolution and
      independently of palaeontological data. Cladistic analysis of elements of
      secondary structure of varible areas V7 and V2 in 18S rRNA with different
      Protozoa as "external" groups shows that Bilateria + Cnidaria are monophyletic,
      Ctenophora and Porifera are early derivatives of Metazoa, Trichoplax (Placozoa)
      is a form related to Cnidaria, while Rhombozoa, Orthonectida and Myxozoa were
      branched within Bilateria. Morphological reduction with losses of any organs and
      tissues took place many times in early evolution of Metazoa and Bilateria not
      only in parasitic species. It occurred both at early and late stages of embryonic
      development and differentiation. Two alternative scenario of morphological
      degeneration in Trichoplax and the way of their testing are suggested. The
      similarity of Ctenophora and Calcarea is discussed. Meridional or oblique
      position of the third cleavage furrow of ovule can be considered as an evidence
      of their origin from common ancestor.

PMID- 12070940
TI  - [A case of tongueworms (Pentastomida): a specific problem in context of the
      modern phylogenetics].
AB  - A short essay on anatomy, ultrastructure and larval development, life cycles,
      classification, palaeontology and phylogenetic relationships of Pentastomida is
      given. Currently, the Pentastomida are usually placed within Crustacea, as sister
      group of Branchiura (Crustacea, Maxillopoda). The grounds are striking
      similarities in ultrastructures of spermatozoa and congruence in the 18S rRNA
      nucleotide sequence. Both taxa are however sharply disparate in all other
      characters concerning morphology, embryology, life cycles and geological history.
      A direct introduction of Pentastomida in the system of Crustacea implies an
      unjustified inflation of the taxonomic diagnosis of the latter group; hence it is
      unacceptable. Two alternative hypotheses are suggested as tentative phylogenetic
      relationships to be tested. Each hypothesis infers however a very complex and
      unlikely evolutionary scenario. 1) Pentastomida and Branchiura are true sister
      groups as justified by coincidence in spermatozoan ultrastructure and sequence of
      ribosomal RNA. Since their divergence, the evolutions of pentastomids and
      branchiurans ran in different milieus, in different shapes and with different
      rates. To present time, the pentastomids lost nearly all characters of
      maxillopods and crustaceans as well as majority of anthropod features. 2)
      Pentastomida and Branchiura are not close related. The similarity in
      ultrastructural details of spermatozoa may be occasional or resulted from
      convergent evolution with unknown factors. Coincidence in nucleotide sequences or
      ribosomal RNA should be reexamined and tested with other pentastomid species. The
      second hypothesis seems to be more likely.

PMID- 12070941
TI  - [On similarities and differences between morphological concepts of Linnaeus and
      Goethe].
AB  - Analysis of C. Linnaeus' and J.W. Goethe's morphological ideas shows that they
      both deal with structure of object under study however Linnaeus understood it
      perceptive structure while Goethe as its proper structure. Perceptive structure
      is an image (Gestalt) formed in observer's mind and recognized by the
      discriminating traits. The proper object structure is composed of its
      morphological elements, that can be distinguished only by a special study of
      their transformations. Notion of the plants modular construction originated
      within Goethe's ideas about plant morphology. We cannot expect any remarkable
      advances in modular theory as well in the descriptive and constructive morphology
      until conceptual differences between these two approaches will be understood.

PMID- 12070942
TI  - [Once again about "Gregg paradox" and its solution].
AB  - "Gregg paradox" means that monotypical groups containing the same species (or
      groups of species) will be equal each other although systematics considers them
      as different taxa. Thus if the order of placental mammalia Tubilidentata includes
      one species aardvark Orycteropus after, the order itself, its single family
      Orycteropodiaceae, single genus of the family Orycteropus and the single species
      Orycteropus after can be considered as equal to each other. To solve this
      disagreement the author asserts that taxa of any level can be regarded as an
      individual according to the taxa of higher rank. Possibility of such
      interpretation was already suggested by Georg Cantor (1985). He supposed that a
      set (class) can be regarded as unity by itself. In this case connections between
      taxa of different levels can be realized by Peano ratio of intrasitive
      conformities. In this model a genus will consist of species but not individuals,
      a type--of classes, etc. Thus, if a taxon x as an individual is an element of
      taxon y, and taxon y as an individual is an element of taxon z, then z according
      to x will be not only logical class, but class of classes and, hence we could not
      consider x as an element of z, because the latter consists of indecomposable
      individual-class y or some similar classes. In this situation "Gregg paradox"
      does not arise.

PMID- 12070943
TI  - [Energy balance of a plant under normal and unfavourable conditions].
AB  - Two main components of plant energy balance are analyzed--photosynthesis and dark
      respiration. Different plant species, growing in optimal conditions and differing
      in photosynthetic metabolism, productivity and potential resistance to stress,
      have constant ratio between total dark respiration and grossphotosynthesis. The
      ratio about 38-40% at the phase of active growth. This value reflect plant state,
      when income (assimilation) is maximized, and expense (total oxidation) is
      minimized. Intensities of dark respiration of plants in darkness and light are
      similar despite the fact that the plants have considerable differences: 1)
      different carbon sources--young assimilates in light and reserve ones in the
      dark; 2) biochemical modifications (or inhibition) of some stages of dark
      respiration in light; 3) intensification of alternative respiration in
      unfavourable conditions differing in dark and light variants. Ratio between
      intensity of dark respiration and photosynthesis increases in plants growing in
      unfavourable conditions. This increase is more considerable in plants that are
      less resistant to the given stress. Characters of energy balance can be used for
      estimation of physiological status of plants, prediction of resistance and
      potential productivity at seedling stage.

PMID- 12070944
TI  - [The problem of durable resistance of plants to different pests].
AB  - Different hypotheses concerning durable plant resistance against different pest
      were tested: 1) resistance is weak and polygenetically controlled; 2) resistance
      depends on "residual effect" of oligogenes that were overcome by pests. Contrast
      pair of plants and pests were used in experiments: wheat, barley--facultative
      parasite Bipolaris sorokiniana Shoem., wheat--obligate parasite Puccinia
      recondita Rob. ex Desm., sorghum--greenbug Schizaphis graminum Rond. Differential
      interaction between parasite and host plant resulted in their increased
      compatibility under long reproduction of parasite on resistant varieties were
      regarded as criteria of quick overcoming of resistance. The results did not
      support any hypothesis. The rate of adaptation of B. sorokiniana to the resistant
      varieties of wheat and barley did not depend on the level of resistance
      expression (weak, moderate or strong) and genetic control (oligogenic, polygenic
      or cytoplasmatic). It was shown by hybridological analysis that "residual effect"
      of oligogenes of sorghum resistance against greenbug depended on small resistance
      genes, that can be independent or weakly connected with marker oligogene. These
      data allows to doubt in phenomenon of "residual effect" of oligogenes. It was
      shown that non specific pathogenicity of parasitic fungi increased during their
      reproductions on sensitive varieties of plants. Thus, cultivation of sensitive
      varieties causes damage of crop culture non only because of their own losses, but
      also by increasing the infection of moderately resistant varieties.

PMID- 12070945
TI  - [Natural toxins in inter- and intraspecies interaction of human being (elements
      of ethnotoxinology)].
AB  - The author considers the application of natural toxins as arrow poison by Homo
      sapiens from ancient time till today for hunting and ethnic wars on the example
      of natives of Asia, Africa, South America and Oceania. Geographic isolation was
      important determining the spectrum of natural toxin sources and the methods of
      their application. Cellular and molecular mechanisms of arrow poisons effects are
      considered in biogeographical context: aconitin and strychnin in Asia,
      diamphotoxin in Africa, indole alcaloids of plants and steroid alcaloids of
      amphibian in Central and South America, palytoxin in Oceania islands. High
      efficiency and selective effect of natural toxins allow to use them as molecular
      markers in current studies of functional membrane architecture and cellular
      structures. Great differences in pace of civilization development leads to the co
      existence at the beginning of the XXI century ethnic groups that use natural
      toxins as arrow poison and human beings that use the same toxins in fundamental
      and applied investigations within international scientific society.

PMID- 12070946
TI  - Human immunodeficiency virus infection in children hospitalised with
      tuberculosis.
AB  - The impact of HIV infection on clinical presentation and outcome of tuberculosis
      (TB) was studied in children hospitalised at the Brooklyn Hospital for Chest
      Diseases (BCH), Cape Town over the 2-year period January 1998 to December 1999.
      Clinical data were extracted from a prospectively compiled patient register. Of
      261 children with TB, 114 (median age 24 mths) were not HIV-infected and 36
      (median age 23 mths) were HIV-infected. The HIV status of 111 children (median
      age 37 mths) was not determined. Pulmonary TB with or without extrapulmonary TB
      occurred in 97 (85%) children who were not HIV-infected, 35 (97%) HIV-infected
      children and 87 (78%) of those not tested (p = 0.025). A tuberculin reaction > or
      = 15 mm was elicited in ten (31%) of 32 HIV-infected children, 76 (72%) of 106
      non-HIV-infected and 62 (71%) of those not tested (p < 0.001). Mycobacterium
      tuberculosis was cultured from 116 (49%) of 238 children and drug sensitivity was
      evaluated in 79. Nine isolates (11%) were resistant to isoniazid (INH) and 11
      (14%) to INH and rifampicin (RMP). Two HIV-infected children treated previously
      in BCH for drug-sensitive TB were re-admitted with INH and RMP resistance. Two
      (2%) non-HIV-infected children, six (17%) HIV-infected children and one (1%)
      child with undetermined HIV status died (p < 0.001).

PMID- 12070947
TI  - The post-mortem pathology of HIV-1-infected African children.
AB  - A retrospective review of autopsy findings and medical records in 33 HIV-infected
      children living in a Kenyan orphanage is described. Their ages ranged from 1
      month to 18 years and median age at death was 71 months (range 7-156).
      Respiratory disorders were probably the primary cause of death in 21 (64%), in 19
      (90%) of whom pyogenic parenchymal lung disease was detected. A presumptive
      clinical diagnosis of pulmonary tuberculosis had been made in 14 (67%); these
      children also had a history of recurrent acute lower respiratory tract infections
      (more than four infections/year). At autopsy, however, only one case of
      tuberculosis was identified (disseminated disease). Pneumocystis carinii
      pneumonia was not identified. Primary bacterial meningitis was detected in 33%.
      The associated findings included disseminated Kaposi sarcoma in two children and
      cryptococcal meningitis in one child. It is concluded that pyogenic infections
      are common causes of morbidity and mortality in HIV-1-infected African children.
      Management should include prompt treatment and, if indicated, prophylaxis for
      recurrent bacterial infections, and early evaluation and treatment of pulmonary
      tuberculosis.

PMID- 12070948
TI  - Community-based dietary phytate reduction and its effect on iron status in
      Malawian children.
AB  - This study describes a community-based method used in rural Malawi to remove
      dietary phytate, an inhibitor of iron absorption, and notes an improvement in the
      iron status of ten children who participated in the trial. Phytate was removed by
      soaking maize flour in excess water with phytase and decanting the water before
      cooking the flour. Iron status, as measured by soluble transferrin receptor and
      zinc protoporphyrin, was improved but not normal.

PMID- 12070949
TI  - Overweight and risk of overweight in schoolchildren in the city of Rio de
      Janeiro, Brazil: prevalence and characteristics.
AB  - The association of overweight and risk of overweight with socio-economic and
      demographic variables was investigated among schoolchildren in the city of Rio de
      Janeiro, Brazil between 1995 and 1996. Data were obtained by direct interview and
      physical examination of boys and girls aged between 6 and 11 years in a two
      stage, random sample, population-based survey. Univariate analysis was performed
      on the association between socio-economic and demographic predictors of
      overweight/risk of overweight and the dependent variables, i.e. body mass index
      (BMI), triceps skinfold and subscapular skinfold. Based on this analysis,
      logistic regression models were developed. The prevalence of overweight and risk
      of overweight was 37.8% in girls and 36.4% in boys. For the BMI model, the
      variables retained were age and number of persons per household; for the triceps
      skinfold model, the variables were age, gender and area of residence; and age,
      gender and persons/household were the variables for the subscapular skinfold
      model. The results suggest that both BMI and skinfold indicators should be used
      to assess overweight/risk of overweight and that public health programmes for
      schoolchildren should be developed to combat the alarming increase in obesity.

PMID- 12070950
TI  - Management of meningitis in children with oral fluid restriction or intravenous
      fluid at maintenance volumes: a randomised trial.
AB  - A multi-centre randomised open trial was done to determine whether moderate oral
      fluid restriction or intravenous fluid at full maintenance volumes would result
      in a better outcome for children with bacterial meningitis in Papua New Guinea,
      and what clinical signs could guide fluid management. Children with clinical
      signs and cerebrospinal fluid suggestive of bacterial meningitis received either
      breast milk by nasogastric tube at 60% of normal maintenance volumes (n = 172) or
      intravenous half-normal saline and 5% dextrose at 100% of normal maintenance
      volumes (n = 174) for the 1st 48 hrs of treatment. An adverse outcome was death
      or severe neurological sequelae, and a good outcome was defined as intact
      survival or survival with at worst mild-to-moderate neurological sequelae. The
      probability of an adverse outcome was 24.7% in the intravenous group and 33.1% in
      the oral-restricted group, but the difference was not statistically significant
      (RR 0.75, 0.53-1.04, p = 0.08). Sunken eyes or reduced skin turgor at
      presentation were risk factors for an adverse outcome (OR 5.70, 95% CI 2.87
      11.29) and were most strongly associated with adverse outcome in the fluid
      restricted group. Eyelid oedema during treatment was also a risk factor for an
      adverse outcome (OR 2.54, 95% CI 1.36-4.75) and eyelid oedema was much more
      common in the intravenous group (26%) than in the restricted group (5%). For many
      children with bacterial meningitis in less developed countries, moderate fluid
      restriction is unnecessary and will be harmful; a normal state of hydration
      should be achieved but over-hydration should be avoided. Giving 100% of normal
      maintenance fluids, especially with intravenous hypotonic fluid, will lead to
      oedema in up to one quarter of children with bacterial meningitis. If additional
      intravenous fluids are required for children with meningitis, an isotonic
      solution should be used.

PMID- 12070951
TI  - Decline in the frequency of Burkitt's lymphoma relative to other childhood
      malignancies in Ibadan, Nigeria.
AB  - Burkitt's lymphoma is the commonest childhood malignancy in tropical Africa and
      the predisposing factors include malaria and infection with the Epstein-Barr
      virus. Recent studies suggest that the prevalence of this neoplasm is declining
      in this environment. The present study was undertaken to investigate whether
      there is a real decrease in the occurrence of Burkitt's lymphoma. We analysed 665
      cases of childhood malignancies reported in the Ibadan Cancer Registry between
      1991 and 1999. Burkitt's lymphoma and retinoblastoma remained the two commonest
      specific childhood malignancies, accounting for 19.4% and 17.9% of all childhood
      cancers, respectively. However, this represents a significant decline in the
      relative frequency of Burkitt's lymphoma when compared with similar surveys for
      the periods 1960 to 1972 and 1973 to 1990 when Burkitt's lymphoma accounted for
      51.5% and 37.1%, respectively, of all childhood malignancies. In Ibadan, it seems
      that what appeared to be minor changes might actually be a real decline in the
      incidence of Burkitt's lymphoma and that it might be partly ascribed to improved
      living conditions and greater control of malaria.

PMID- 12070952
TI  - Retrospective comparison of management of gastro-enteritis in hospitalised
      children.
AB  - In Hong Kong, bacterial pathogens, the majority of them Salmonellae, cause
      approximately one-third of paediatric admissions for diarrhoea. This study
      retrospectively reviewed inpatient gastro-enteritis management, with particular
      focus on antibiotic use. Antibiotics are generally recommended for Salmonella
      gastro-enteritis in infants under 3 months of age but not for older infants and
      children unless they are so toxic that bacteraemia is suspected. Three groups of
      children admitted with acute gastro-enteritis were randomly identified from a
      computerised discharge database. Based on pathological reports held in the case
      records department, the final groups for analysis were Salmonella (n = 86),
      rotavirus (n = 55) and non-specified (n = 126). Epi Info version 6 (CDC, Atlanta)
      was used for data entry and analysis. Compared with a combined rotavirus/non
      specified group, the Salmonella group were significantly more likely to have
      blood (OR 6.1, 95% CI 3.2-11.7, p < 0.0001) and mucus (OR 4.8, 95% CI 2.6-8.9, p
      < 0.0001) in the stool, fever during admission (OR 3.6, 95% CI 1.6-8.4, p =
      0.001), more stools per day (median 6.2 vs 4.2, p < 0.0001), a longer stay in
      hospital (median 3.4 vs 2 days, p < 0.0001) and to be younger (median 7.1 vs 14.6
      mths, p < 0.0001). The Salmonella group were more likely to have been given
      antibiotics (38% vs 15%, OR 3.6, 95% CI 1.9-6.9, p < 0.0001) but age did not
      influence the likelihood that antibiotics would be given.

PMID- 12070953
TI  - Anorexia nervosa in early adolescence in Sri Lanka.
AB  - We report four cases of anorexia nervosa (AN) seen over a period of 5 months in
      the psychiatry unit of a general hospital. The report is unusual because two of
      the patients were male, all were between 13 and 15 years of age and AN is thought
      to be rare in Sri Lanka. All four patients had features typical of AN. There are
      implications for clinical practice in Sri Lanka if the prevalence of AN is rising
      because all these patients presented to psychiatrists late in their illness, some
      in an advanced state of weight loss.

PMID- 12070954
TI  - Congenital tuberculosis associated with maternal asymptomatic endometrial
      tuberculosis.
AB  - This is a report of a 4-month-old baby girl who presented with respiratory
      distress, bronchopneumonia, marasmus and hepatosplenomegaly and proved to have
      congenital tuberculosis on the basis of a strongly positive Mantoux test and
      liver biopsy findings. Endometrial biopsy in the asymptomatic mother confirmed
      the source of infection and the perinatal onset of illness. The age range of
      previously reported cases of congenital tuberculosis is 1-84 days and this case
      would appear to be the latest presentation of congenital tuberculosis in the
      literature.

PMID- 12070955
TI  - Typhoidal focal suppurative lymphatic abscess.
AB  - We describe a submandibular suppurative lymphatic abscess caused by Salmonella
      typhi in an 8-year-old child. The diagnosis was confirmed by repeated isolation
      of S. typhi from the abscess. A literature search found no previous report of a
      similar nature and this therefore seems to be the first case report of focal
      suppurative typhoidal lymphatic abscess. The child responded to cephalexin and
      surgical drainage.

PMID- 12070956
TI  - Mycetoma of the sole.
AB  - We report a case of mycetoma of the sole of the foot in a 10-year-old caused by
      Nocardia brasiliensis. It was treated successfully with a combination of
      trimethoprim-sulfamethoxazole, dapsone and rifampicin.

PMID- 12070957
TI  - Severe congenital rickets secondary to maternal hypovitaminosis D: a case report.
AB  - We report a full-term baby boy who presented soon after birth with severe
      congenital rickets. Maternal and neonatal vitamin D levels were very low and the
      infant responded well to oral vitamin D. Transient secondary hyperparathyroidism
      normalised on treatment. The mother's vitamin D deficiency was attributed to the
      region's cultural dress code which prevents exposure to sunlight. There has not
      been a previous report of severe congenital rickets from this region.

PMID- 12070958
TI  - Urinary tract pathogens and their antimicrobial sensitivity patterns in children.

PMID- 12070959
TI  - [Effect of different concentrations of heavy metal ions on the normal physical
      and chemical characteristics of the hemolymph of Palanorbarius purpura (Mollusca:
      Bulinidae) in the norm and during a trematode infection].
AB  - Short-term simultaneous effect of high concentrations (LC25, LC50, LC75) of heavy
      metal ions. (Cu2+, Zn2+, Cd2+ and Pb2+) and infection with trematode partenites
      Echinoparyphium aconiatum onto haemolymph of mollusk has been investigated. It
      was noted that low doses of toxicant (2.5 and 10 maximum admitted concentrations)
      have variable effect. In infected molluscs the concentration of haemoglobin
      decreases, while in intact ones it increases. In relation to this index, it was
      found, that the ion Cu2+ is highly toxic, Zn2+ and Cd(2+)--toxic, Pb(2+)-
      moderately toxic.

PMID- 12070960
TI  - [Revision of Aploparaksis crassirostris and A. sinensis (Cestoda:
      Hymenolepididae)].
AB  - Based on the examination of specimens of Apoloparaksis crassirostris deposited in
      the Museum of Zoology in Copenhagen and the Museum of Natural History in Geneva
      and cestode material from other collections, we have carried out the revision of
      this species, designated the lectotype and paralectotypes, made its
      redescriptions, enumerated synonyms, showed the only host of this species in the
      snipe Gallinago gallinago, and more precisely mapped the distribution range of
      the parasite. The investigation of the type series of A. sinensis, the parasite
      of the woodcock Scolopax rusticola, deposited in the Museum of Natural History in
      Geneva, confirmed the validity of this species, earlier considered as synonym of
      A. crassirostris. The lectotype and paralectotypes of A. sinensis were
      designated. Some data on its life cycle have been obtained. It was also found by
      the experimental invasion that five species of oligochaetes of the family
      Lumbricidae are intermediate hosts. The metacestodes of this species belongs to
      the tailed diplocyst modification and posesses a characteristic feature, the
      bifurcation of tail.

PMID- 12070961
TI  - [Invasion of fish with leeches (Fam. Piscicolidae) in reservoirs of the Volga
      river].
AB  - It is shown for the first time that during 50 years of the Rybinsk reservoir's
      existence the abundance of parasite leeches (Piscicolidae) has increased, and the
      species composition has become richer. In 70 the leech Caspiobdella fadejewi
      (Epstein) was registered here as a mass species. This species became a real
      competitor to Piscicola geometra (L.) inhabiting the Volga river in all times. In
      early '90s the leech Acipenserobdella volgensis (Zykoff) appeared in the Rybinsk
      reservoir. Till 1987 this species was not found to the north from the Kuibyschev
      reservoir. An increase in number of fish leeches and an extension of their
      specific composition occurred not only in the Rybinsk reservoir but in the other
      reservoirs of the Volga cascade as well.

PMID- 12070962
TI  - [Ectoparasite infection of some fish species in lake Pleshcheev].
AB  - Ectoparasites have been investigated on gills of the ruff, perch, white bream,
      roach, bream, ide, and European cisco from the Pleshcheevo lake. 13 parasite
      species were found: Dactylogyrus falcatus, D. distinguendus, D. cornoides, D.
      cornu, D. sphyrna, D. robustus, D. amphibothrium, Ancyrocephalus paradoxus,
      Argulus foliaceus, Ergasilus sieboldi, Achtheres percarum, Ancyrocephalus percae,
      and Rhipidocotyle companula. A reliable negative correlation between the number
      of monogeneans An. paradoxus and the copepods Ac. percarum on the perch. D.
      falcatus, the specific monogenean of the bream, was found on the roach. The
      comparison of the obtained data with those of 1939 has shown the decrease of
      oxyphilic copepods E. seiboldi, that prove the increasing eutrophication.

PMID- 12070963
TI  - [Dactylogyrids (Monogenea: Dactylogyridea) with an unusual number of anchors,
      their origin and phylogenetic significance. Reference data].
AB  - It is considered that in Anacanthorinae, Markewitschiana and Pseudacolpenteron
      pavlovskii (Dactylogyridae s. s.) the anchors are absent originally. In the other
      dactylogyrids (s. l.) without anchors (Pseudacolpenteron ignotus; Acolpenteron;
      Anonchohaptor-Icelanchohaptor; Kritskyia-Telethecium-Pavanelliela) these
      structures are lost. In related genera Rhinoxenus and Nanotrema the dorsal pair
      of anchors is transformed into the "spikes"; in Heteronchocleidinae there is one
      anchor; in Trinigyrus and Schilbetrematoides are two anchors; and in Urogyrus
      three anchors are reduced. But in Rhinonaster, Cacatyocotyle, Callceostomella,
      Neocalseostoma elongatum and Pseudodactylogyridae the presence of one pair of
      ventral "peduncular" or "haptoral" anchors appear to be the original state. For
      Anacanthorinae and Dactylogyridae s. s. the presence of 18-16 hooks, original
      lacking of anchors, appearance of one pair of them, evolutionary development and
      subsequent reduction of these structures are characteristic. In the dactylogyrids
      (s. l.) having two pairs of anchors and 14 hooks, one pair of the anchors is
      present originally, then usually the second dorsal pair grows up, and finally,
      the reduction of a part of anchors or all the anchors is possible. In the 16
      hooked dactylogyrids (s. l.) having two pairs of anchors (Tetraonchinea,
      Amphibdellainea, Neodactylodiscinea) the original lacking or reduction of the
      anchors is not reported. The author considers, that it is unwarranted to unite
      all dactylogyrids (s. l.) without anchors into the superorder Ananchorea
      Malmberg, 1990 or to postulate the original presence of the two pairs of ventral
      anchors in this group. It is also impossible to unit all dactylogyrids (s. l.)
      having 0-4 anchors and 18-14 hooks into Dactylogyridae sensu Boeger et Kritsky,
      1993.

PMID- 12070964
TI  - [Effect of the parasitic dinoflagellate Ellobiopsis chattoni (Protozoa:
      Mastigophora) on the winter mortality of the calanoid copepod Calanus
      finmarchicus (Crustacea: Copepoda) in the Norwegian Sea].
AB  - We studied the effects of the parasitic dinoflagellate Ellobiopsis chattoni on
      the winter mortality of natural population of the calanoid copepod Calanus
      finmarchicus in the Norwegian Sea (materials was collected in March-April 1989
      and September 1990). Dinoflagellate infection occurred during autumn (the
      infection rates of copepods with E. chattoni was 15%, as average). Average
      mortality rate in C. finmarchicus was about 0.08% per day, or about one-tenth of
      total mortality in winter period.

PMID- 12070965
TI  - [Repeated finding of the North American ciliate Ambiphrya ameiuri (Peritricha:
      Scyphidae) in the Rybinsk reservoir].
AB  - The first case of a mass infection of fish fry with the ciliate Ambiphrya ameiuri
      (Thompson e. a., 1946) was found during the summer of 1989 in one of spawning
      zones of the Rybinsk reservoir. In June-July of 2000 after the ten-year interval,
      the second case of infection with this parasite in the first-year roach Rutilus
      rutilus has been observed. The prevalence of A. ameiuri was very low. Nine other
      species of ciliates forming the ectoparasite community were also observed.
      Parasites were disposed mostly on a surface fish bodies, gills and more densely
      on fins.

PMID- 12070966
TI  - [Myxosporidian fauna from Gadidae in the Far East Sea].
AB  - The myxosporidian fauna of the Gadidae from Far Eastern seas have been
      investigated. 7 species of myxosporidians of two families have been found
      Redescriptions of myxosporidian species are given.

PMID- 12070967
TI  - [Some aspects and perspectives of factor prognosis for the epidemic manifestation
      of tick-borne encephalitis based on a multidimensional analysis of temporal
      rows].
AB  - A method of factor temporal prognosis for the epidemic manifestation of the tick
      borne encephalitis foci has been elaborated, based on recognized critical levels
      of infection. High reliability of possible prognoses and obvious perspectives of
      the proposed method are noted.

PMID- 12070969
TI  - Perceptions of influenza and influenza vaccination in patients attending hospital
      outpatient clinics.
AB  - Influenza remains a major cause of morbidity and disruption to health services
      during winter. Annual vaccination of risk groups is the mainstay of influenza
      management policy. Despite much national publicity, vaccine uptake remains below
      desired levels. We investigated the perceptions of influenzal illness and
      opinions on vaccination in hospital outpatients attending clinics associated with
      risk and non-risk (i.e. control) morbidities. There were 270 recruited patients
      in risk groups: 90 each from diabetic, respiratory and cardiac clinics and equal
      numbers in three age groups (40-49, 50-59, 60-69 years). Equal numbers of
      controls were recruited from colorectal, fracture and dermatology clinics. The
      perceptions of influenza and knowledge of the preventive value of vaccination
      were fairly accurate in both groups. Fewer people in both groups had been
      vaccinated than had been specifically advised to be vaccinated. Advice for
      vaccination had been received by fewer people attending the cardiac clinic than
      the other two risk associated clinics. More use could be made of the health
      education opportunity afforded by attendance at hospital outpatient clinics.

PMID- 12070968
TI  - [Ultrastructure of epithelium and ciliary receptors in the parasitic turbellarian
      Urastoma cyprinae (Turbellaria, "Prolecithophora") and position of the species
      within Platyhelminthes].
AB  - Ultrastructure of the epithelium of adult and juvenile Urastoma cyprinae has been
      studied. The epithelium of both adult and juvenile worms is cellular, ciliated
      and bears numerous microvilli. The cytoplasm is rich in large, numerous
      epitheliosomes of two types--electron-dense and with fibrillated content (fig. 1,
      a, [symbol: see text]; 2, a-[symbol: see text]). Besides large secrete granules
      small membrane-bounded vesicles were observed (fig. 2, a-[symbol: see text]). In
      juvenile worms the dense epitheliosomes are less abundant and the fibrillated
      content in the second type of granules has a different structure: the fibrils are
      very thin and more densely packed forming the structures of the less electron
      density (fig. 3, a, [symbol: see text], [symbol: see text] 1). The membrane
      bounded vesicles in the epithelium of juvenile worms were not observed. All types
      of secrete are ejected by exocytosis (fig. 2, [symbol: see text]; 3, [symbol: see
      text], [symbol: see text]). The ultrastructure of the epithelium in juvenile U.
      cyprinae is strongly similar to that in parasitic turbellarian Kronborgia,
      especially to the epithelium in a male and a larva. The basal lamina consists of
      tree layers and forms numerous deep infoldings into the epithelium (fig. 1, a; 2,
      a; 3, a, [symbol: see text], [symbol: see text]). The basement membrane projects
      deep and numerous invaginations into the epithelium which may almost reach the
      apical membrane (fig. 1, a; 2, a, [symbol: see text], [symbol: see text]; 3,
      [symbol: see text]). Mitochondria are large and situated mainly near the
      projections of the basement membrane (fig. 2, [symbol: see text]-[symbol: see
      text]; 3, [symbol: see text]). Such ultrastructure implies an intensive process
      of the transmembrane transfer of the dissolved organic substances from the sea
      water. The same structures were found in the epithelium of Kronborgia. Uptake of
      organic compounds through the epithelium in the common ancestors of Urastoma and
      Kronborgia could be the preadaptation to the endoparasitic mode of life in
      Fecampiida. The differencies in ultrastructure of epithelium in U. cyprinae from
      the White Sea and from Mediterranean Sea (Noury-Srairi e. a., 1990) may be
      explained by the differences in the method of fixation or by the parasitizing the
      another host--the mollusk Mytilus galloprovincialis. The ciliary receptors of
      five types were revealed in U. cyprinae (fig. 3, e, [symbol: see text]; 4; 5; 6).
      They differ in the shape and length of the ciliary rootlets and in the content of
      the nerve processes. All receptors lack of the real collars typical for the
      receptors of Neodermata. Urastoma is most close to the Neodermata amond parasitic
      turbellarians studied thus far, and the absence of collars in receptors of this
      species testifies that the collars are the veritable synapomorphy of the
      Neodermata. The diversity in the ultrastructure and possible functions of
      receptors correspond to the complicated adaptations of this species. The modern
      molecular data as well as the ultrastructural evidence attest that parasitic
      turbellarians of the genera Urastoma, Genostoma and Ichthyophaga are relatives
      and cannot be included in any turbellarian order known. Therefore Urastoma,
      Genostoma and Ichthyophaga have been erected in the separate order Urastomida
      ord. nov. The diagnosis of the new order is given.

PMID- 12070970
TI  - Local surveillance of influenza in the United Kingdom: from sentinel general
      practices to sentinel cities?
AB  - Surveillance of influenza in England and Wales utilises a disparate geographical
      network of general practices to provide clinical data in the form of weekly
      consultation rates for influenza and 'influenza-like illness'. This network
      accurately detects and monitors seasonal influenza activity at national and supra
      regional levels. Localised regional and sub-regional epidemics are less easily
      detected. We describe a localised epidemic of influenza affecting a deprived
      urban community in the North West of England that was detected by a close knit
      network of general practices participating in the surveillance of communicable
      diseases as part of a primary care health needs assessment initiative.

PMID- 12070971
TI  - Getting ahead of the curve while shifting the balance of power--a CCDC's view.

PMID- 12070974
TI  - Survey of public health laboratory protocols for reporting the antibiotic
      susceptibility of urinary isolates submitted from general practice.
AB  - This study set out to investigate the variation in laboratory reports of the
      antibiotic susceptibility of urinary isolates from specimens received from
      primary care. A questionnaire survey was conducted across Public Health
      laboratories in England and Wales, and 38 out of 47 questionnaires were returned.
      Seventy-nine percent of laboratories had community antibiotic guidelines for the
      management of urinary tract infections, and trimethoprim was the most common
      first-line antibiotic recommendation. Trimethoprim and nitrofurantoin were the
      most commonly tested antibiotics, and the oral cephalosporins were the most
      frequent second-line antibiotics tested. A wide variation in reporting was
      demonstrated, with 47% of laboratories reporting on the combination of
      trimethoprim, amoxycilline and an oral cephalosporin. In view of the increasing
      concern about antibiotic prescribing in the community, it may be useful to review
      local laboratory policies so that antibiotic susceptibility reporting is
      consistent with primary care antibiotic guidance.

PMID- 12070973
TI  - Audit of suspected meningitis in a district in 1996-1997 and in 1999.
AB  - The Public Health Laboratory Service has published guidance outlining appropriate
      investigations and public health action to control the spread of meningococcal
      disease. We investigated compliance with this guidance in audits of suspected
      meningitis cases in our district notified to the public health department between
      January 1996 and December 1997, and in 1999. The total number of suspected
      meningitis cases in 1996-7 and in 1999 were 58 and 34 respectively. Meningococcal
      disease was suspected in 49 and 28 patients respectively, and for 58 (75.3%) of
      these case notes were found. Rash was more often a presenting sign in 1999. The
      second audit also showed a non-significant reduction in the proportion of
      patients given penicillin before hospital admission (22.4% vs. 7.1%, p = 0.12),
      and in CSF microscopy requests (31% vs. 17.6%, p < 0.5). Requests for
      meningococcal investigation by blood culture (77.5% vs. 79.4%, p < 0.5) blood PCR
      (34.5% vs. 64.7%, p < 0.001) and throat swab (25.9% vs. 55.9%, p < 0.005) were
      increased. Notifications of cases to the public health department within 24 hours
      of admission were also increased slightly (42.8% vs. 52.9%; p < 0.5). Changes in
      clinical practice can be achieved through guidelines, audit and feedback. The
      importance of parenteral penicillin administration prior to hospital admission,
      appropriate investigations and prompt public health notification should be re
      emphasised.

PMID- 12070975
TI  - What is needed on a laboratory test request form?
AB  - In the development of a screening programme for genital tract Chlamydia
      trachomatis infection, a modified test request form was devised and used
      successfully both to request the test, to collect data and to inform patients.
      Our examination of the practicalities and ethical and confidentiality issues
      involved in making a request for a laboratory test to assist clinical diagnosis
      or management, resulted in the introduction of extra features that we had not
      previously seen used in the design of request forms. Coded response boxes can
      have adjacent questions attached as a perforated strip. Removal of this question
      strip leaves a completed form with no explicit sensitive data (figure 2). A
      detachable information sheet for patients can also be incorporated into the
      request form (figure 1). The design of a request form raises issues that do not
      appear to have been widely or formally debated.

PMID- 12070972
TI  - Incidence of Pseudomonas aeruginosa in recreational and hydrotherapy pools.
AB  - Pseudomonas aeruginosa remains an important agent of opportunistic infection in
      patients, particularly those with respiratory complications and burns. One
      natural niche of this organism is water and water-associated facilities, hence
      the aim of this study was to examine specimens from recreational and hydrotherapy
      pools in Northern Ireland over a two-year period. Water specimens (n = 3,510)
      were obtained from three amenity categories, namely, 13 hydrotherapy pools
      (specimen number [n] = 323), 51 Jacuzzis/spas (n = 1,397) and 68 swimming pools
      (n = 1,790). Specimens (100 ml) were filtered through a cellulose acetate (0.45
      micron pore size) gridded filter and the membrane was placed on Pseudomonas CFC
      agar (Oxoid CM559 + SR103) and incubated at 37 degrees C for 48 +/- 2 h. Colonies
      that clearly showed pyocyanin production or met other identification criteria
      were considered P. aeruginosa. Of the amenities examined 4/13 hydrotherapy pools
      (30.8%), 37/51 Jacuzzis/spas (72.5%) and 26/68 swimming pools (38.2%) were
      positive for P. aeruginosa. The most heavily contaminated amenity category was
      the Jacuzzi/spa, where 34.7% and 12% of private and public sites respectively
      were positive for P. aeruginosa at a level of greater than 1,000 cfu 100 ml-1.
      Approximately twice as many samples were positive in private Jacuzzis/spas
      compared to publicly operated facilities. There was a similar trend with respect
      to public and private hydrotherapy pools, though bacterial counts did not exceed
      1,000 cfu 100 ml-1. Recreational and therapeutic amenities involving the use of
      water may be a potential source of P. aeruginosa for susceptible patient groups,
      including patients with cystic fibrosis and bronchiectasis. This may vary
      depending on amenity type and public/private ownership of such amenities.

PMID- 12070976
TI  - Sexual health and HIV positive individuals: emerging lessons from the recent
      outbreaks of infectious syphilis in England.

PMID- 12070977
TI  - Practical lessons from the management of an outbreak of small round structured
      virus (Norwalk-like virus) gastroenteritis.
AB  - An outbreak of viral gastroenteritis caused illness in 92 people during October
      2000. All the cases had an association with one hotel and 80% of cases identified
      had attended one of two buffet meals on 18th October 2000. Cohort analysis did
      not implicate any particular foodstuff in this outbreak. All bacteriological
      tests on food samples were negative. Small round structured virus (SRSV)/Norwalk
      like virus (NLV) particles were seen by electron microscopy in 6 out of 27 stool
      samples submitted for analysis. This paper describes the outbreak and in
      particular the lessons learned from the management and control of it. These
      include practical points with regard to the outbreak control team, liaison with
      the microbiology laboratory, handling data, agreeing a case definition, and
      occupational health issues. All can be applied elsewhere by those responsible for
      managing outbreaks at a local level.

PMID- 12070978
TI  - Outbreak of tuberculosis at a Newcastle public house: the role and effectiveness
      of contact screening.
AB  - We report an outbreak of tuberculosis (TB) that originated in a public house,
      involving 12 cases. The presumed index case was a regular patron. Initial
      screening of close contacts identified no further cases. Six cases of TB then
      presented symptomatically among other regular patrons. Contact screening was
      extended to include all regular patrons and bar staff. In total, 110 individuals
      were screened. One case was detected and three children were placed on
      chemoprophylaxis. Transmission of M. tuberculosis between patrons of a public
      house may cause community outbreaks of TB. Where cases present outside a close
      contact screening program, extended contact screening must be considered.

PMID- 12070979
TI  - Outbreak of Vero cytotoxin-producing Escherichia coli O157 in a child day care
      facility.
AB  - In December 1998, an outbreak of Vero cytotoxin-producing Escherichia coli (VTEC)
      O157 in a creche affected ten out of 45 children and one out of five staff
      members. Eight cases were symptomatic and three were asymptomatic. There were two
      asymptomatic adult family contacts of child cases. All specimens were identified
      as VTEC O157:H7, phage type 32. None of the cases were seriously ill and none
      developed haemolytic uraemic syndrome (HUS). One child continued to excrete the
      organism for 14 weeks. The origin of the outbreak was not found but
      epidemiological investigation was suggestive of person-to-person spread. All
      children and staff were screened and excluded from the creche until
      microbiological clearance was obtained. An inspection of the creche revealed
      overcrowding and inadequacies in cleaning and in the food preparation facilities.
      These problems were remedied before children were re-admitted to the creche. This
      outbreak demonstrates the ease with which VTEC O157 can be transmitted between
      small children. Two specific features of this outbreak were notable: (1) the mild
      self-limiting nature of the illness and (2) the prolonged shedding of the
      bacterium by one child.

PMID- 12070980
TI  - Guidelines on the management of, and exposure to, rash illness in pregnancy
      (including consideration of relevant antibody screening programmes in pregnancy).
AB  - These guidelines, produced by the Public Health Laboratory Service (PHLS) aim to
      help decision making in the investigation and management of pregnant women who
      have 'a rash compatible with a systemic viral illness', or who have contact with
      a person with such an illness. They address particularly rubella, parvovirus B19,
      and varicella-zoster virus infection, but consider other infective causes of rash
      illness in the United Kingdom. The guidelines give the magnitude and degrees of
      risk to the fetus in terms of outcomes for the gestation at which maternal
      infection occurs. Recent changes in epidemiology and management lead to the
      following specific advice, which both updates and re-affirms established
      guidelines. All pregnant women with a non-vesicular rash illness should be
      investigated simultaneously for rubella and parvovirus B19 infection. All
      pregnant women who have had significant contact with a person suffering from a
      non-vesicular illness should be investigated for asymptomatic parvovirus B19
      infection, and for asymptomatic rubella infection unless there is satisfactory
      evidence of past rubella infection (vaccine or natural infection). A significant
      contact is defined as being in the same room for over 15 minutes, or face-to-face
      contact. Specific investigation to detect asymptomatic rubella reinfection is not
      advised. It is essential to confirm by adequate laboratory investigation all
      cases of possible rubella and parvovirus B19 infection in pregnancy. Management
      of proven rubella in pregnancy should be based on established risks of adverse
      outcome. Women with proven parvovirus B19 infection in the first 20 weeks of
      pregnancy should be followed by regular, ultrasound scanning, and referred to
      Regional Units of Fetal Medicine if hydrops fetalis is detected. Parvovirus B19
      antibody screening in pregnancy is not advised, and consensus has been reached on
      the procedures to be followed for rubella antibody screening, including the
      concentration of antibody that reflects past infection. Oral antiviral treatment
      (aciclovir) is advised with informed consent for pregnant women who present
      within 24 hours of onset of varicella. Referral to hospital and intravenous
      antiviral treatment is indicated for pregnant women with complications and/or
      risk factors, or whose illness continues for six days or more. Pregnant women
      exposed to varicella or herpes zoster can be reassured as to their protection if
      they themselves have a history of varicella or herpes zoster. If this history is
      uncertain or not known, susceptibility should be tested, and varicellazoster
      immunoglobulin (VZIG) offered to those found susceptible if within 10 days of
      first exposure. Infants whose mothers develop varicella 7 days before to 7 days
      after delivery should be given VZIG, and aciclovir if onset was 4 days before to
      2 days after delivery.

PMID- 12070981
TI  - Impact of infections on primary care--greater than expected.
AB  - Though infection has declined as a cause of death it consumes a major proportion
      of primary care resources, and because of antibiotic resistance is increasingly
      important. We examined the burden of illness attributable to infection in primary
      care by analysing data from the fourth practice-based national morbidity survey
      which monitored all consultations by diagnosis in 470,000 persons over a 12 month
      period from September 1991 to August 1992. Rates of persons consulting, new
      episodes of illness and consultations were calculated according to the list of
      infections published by Wilson and Bhopal (W&B list), and as amended by the
      Communicable Disease Surveillance Centre (CDSC list); selected comparisons were
      made with national data on hospital derived finished consultant episodes and
      deaths. Forty-one percent of all registered persons consulted on at least one
      occasion during the year for infection (estimated by either list). Infections
      accounted for 40% of all new episodes of illness and 29% of all consultations;
      respiratory infections accounted for approximately half the infection total. New
      episode rates were highest in children aged less than 1 year and lowest in males
      25-54 years and females 55-64 years. Except in infancy, rates were higher in
      females. There were 734 episodes of infection annually per 1,000 population
      reported in general practice compared with 20 per 1,000 finished consultant
      episodes. The average episode of infection prompted 1.2 general practice
      consultations. Improved management through more precise diagnosis by near patient
      tests is desirable, but is unlikely to be obtained cost effectively if
      consultation numbers or the time spent is substantially increased. These results
      emphasise the importance of adequate training for general practitioners in the
      natural history, epidemiology, diagnosis and treatment (pharmacology) of
      infection.

PMID- 12070982
TI  - Congenital syphilis following negative antenatal screening.
AB  - We report a case of severe early congenital syphilis in the infant of a mother
      who acquired syphilis in mid pregnancy. The mother had received full antenatal
      care including serological screening for syphilis. Congenital syphilis is re
      emerging in a number of industrialised countries and this report demonstrates
      that some of the most serious cases cannot be prevented by routine antenatal
      screening.

PMID- 12070983
TI  - A case of meningococcal disease in a schoolgirl previously given meningococcal C
      vaccine.

PMID- 12070984
TI  - Wild rabbits--a novel vector for Vero cytotoxigenic Escherichia coli (VTEC) O157.

PMID- 12070986
TI  - One hundred years of virology: a chief's perspective.
AB  - The ubiquitous nature of viruses has had its impact throughout the living world.
      Virus disease can be found in higher animals, birds, plants, arthropods, protozoa
      and bacteria. Viruses are no modern phenomenon, although it is only in the last
      50 or so years that a fuller knowledge of their biological, chemical and physical
      properties has emerged. This short account recalls the development of human
      virology in particular, from the first discovery of a 'filterable virus' in 1892
      to the spectacular technological breakthroughs during the 1950's and 1960's,
      leading to the molecular virology of today. This account was written to accompany
      an exhibition of artefacts displayed during the IBMS Congress in Birmingham in
      September 2001.

PMID- 12070985
TI  - Biotech versus bioterror.

PMID- 12070987
TI  - The underlying causes of accidents.
AB  - Many theories about the causation of accidents have developed over years, some of
      which are very complex. Often, multiple causes can be identified. Often, too, it
      is tempting to deal with the most obvious ones and ignore the others, which may
      be more difficult to address. Using a fairly straightforward approach, the causes
      of accidents can be divided in two main types, 'immediate' or 'primary', and
      'indirect' or 'secondary'.

PMID- 12070988
TI  - Analysis of basement membrane self-assembly and cellular interactions with native
      and recombinant glycoproteins.

PMID- 12070989
TI  - Matrix and meaning.

PMID- 12070990
TI  - Preparation and analysis of synthetic multicomponent extracellular matrix.

PMID- 12070992
TI  - Cell-matrix adhesion research and the development of biotherapeutics.

PMID- 12070991
TI  - Analysis of matrix dynamics by atomic force microscopy.

PMID- 12070993
TI  - Analysis of matrix degradation.

PMID- 12070995
TI  - Purification of integrins and characterization of integrin-associated proteins.

PMID- 12070994
TI  - Expression cloning strategies for the identification of adhesion molecules.

PMID- 12070996
TI  - Methods for analysis of the integrin ligand binding event.

PMID- 12070997
TI  - Intracellular coupling of adhesion receptors: molecular proximity measurements.

PMID- 12070998
TI  - Detection and purification of instructive extracellular matrix components with
      monoclonal antibody technologies.
AB  - Historically, Mabs have been one of the most productive and reliable methods for
      the identification of adhesion receptors and adhesive ECM ligands. In large part,
      this is because Mabs can identify the function of the adhesion components within
      the context of the complex ECM or the cell surface. There are now many isoforms
      of laminin, collagen, and other ECM components that have been identified by
      molecular and Mab approaches. It is not clear when and where these isoforms are
      expressed at the protein level, nor what unique functions each ECM isoform may
      serve within the context of tissue. Undoubtedly, specific in vitro assays in
      combination with specific Mabs will help illuminate the instructive roles of ECM
      components for reporter cells within in vitro models and tissue. Delineation of
      cell responses to the instructive ECM will require additional high-resolution
      technologies including DNA microarrays and targeted disruption of ECM components.

PMID- 12070999
TI  - Functional analysis of cell adhesion: quantitation of cell-matrix attachment.

PMID- 12071000
TI  - Measurements of glycosaminoglycan-based cell interactions.

PMID- 12071001
TI  - Methods in cell-matrix adhesion. Introduction.

PMID- 12071002
TI  - Applications of adhesion molecule gene knockout cell lines.
AB  - Cell lines derived from mice carrying targeted mutations in adhesion or ECM
      genes, and ES cell lines homozygous for mutations in these genes, have proved to
      be valuable tools to examine the functions of these molecules in development, and
      at a molecular level by in vitro experimentation. In many cases, the development
      of cell lines has exposed novel phenotypes not apparent from in vivo
      observations, possibly because the in vitro system under observation is more
      dependent on a specific molecule than is an entire organ or organism. These cell
      lines should continue to provide interesting model systems to study the molecular
      function of adhesion receptors.

PMID- 12071003
TI  - Flexible polyacrylamide substrata for the analysis of mechanical interactions at
      cell-substratum adhesions.
AB  - We have described a powerful tool for the study of mechanical interactions
      between cells and their physical environment. Although the approach has already
      been used in a variety of ways to measure traction forces and to characterize
      active and passive responses of cultured cells to mechanical stimulation, it can
      be extended easily and combined with other microscopic approaches, including
      fluorescent analog imaging (Beningo et al., 2001), photobleaching, calcium
      imaging, micromanipulation, and electrophysiology. This method will be
      particularly useful for studying the functions of various components at focal
      adhesions, and the effects of mechanical forces on focal adhesion-mediated signal
      transduction. In addition, the method can be extended to a 3D setting, e.g., by
      sandwiching cultured cells between two layers of polyacrylamide to create an
      environment mimicking that in the tissue of a multicellular organism. Whereas
      chemical interactions between cells and the environment have been investigated
      extensively, many important questions remain as to the role of physical forces in
      cellular functions and the interplay between chemical and physical mechanisms of
      communication. The present approach, as well as other approaches capable of
      probing physical interactions, should fill in this important gap in the near
      future.

PMID- 12071004
TI  - Cell migration in slice cultures.

PMID- 12071005
TI  - Application of cell adhesion to study signaling networks.

PMID- 12071006
TI  - Use of micropatterned adhesive surfaces for control of cell behavior.

PMID- 12071007
TI  - Adenoviral-mediated gene transfer in two-dimensional and three-dimensional
      cultures of mammary epithelial cells.

PMID- 12071008
TI  - Isolation and purification of proteoglycans.

PMID- 12071009
TI  - Expression of recombinant matrix components using baculoviruses.

PMID- 12071010
TI  - Cell-matrix interactions: the view from the outside.

PMID- 12071011
TI  - Heparan sulfate-growth factor interactions.

PMID- 12071012
TI  - [A 59-year-old woman surgically treated for angiocholangitis].

PMID- 12071013
TI  - [The 16th Days of the French Society of Digestive Surgery. Toulouse, December 6
      7, 2001].

PMID- 12071015
TI  - [Re: "Pancreatic excision for chronic pancreatitis and cancer: its foundation for
      "factual" surgery. Published in the Journal de Chirurgie 2001; 138:325-335].

PMID- 12071014
TI  - [Right colonic cystic pneumatosis disclosed by pneumoperitoneum].

PMID- 12071016
TI  - [Few grafts, many patients: organ transplantation imposes a double duty of
      efficiency and equity].

PMID- 12071017
TI  - [Diagnostic and therapeutic management of digestive caustic burns].
AB  - Caustic burns of the upper gastrointestinal tract are a common emergency. Outcome
      is generally favorable. Endoscopic fiberoptic examination is the most accurate
      exam for evaluation of the extent of corrosive injuries. In case of severe
      caustic burns, surgical intervention allows removal of necrotic tissues, and
      prevent the extent of burns to the adjacent organs. Blunt esophageal stripping,
      combined with total gastrectomy is then the intervention of choice. Superficial
      burns usually recover without sequela, or with esophageal or gastric stenosis.
      Secondary coloplasty is advocated for treatment of failure of endoscopic
      dilatations, and for digestive reconstruction after initial esophagogastrectomy.

PMID- 12071018
TI  - [Vascular clamping in hepatic surgery].
AB  - Outcome of hepatectomy procedures depends greatly on proper control of
      intraoperative bleeding. We detail here the different techniques for vascular
      clamping, discussing their different indications. Four parameters can be used to
      define clamping: the zone of application: separate control of arterial or glisson
      pedicles and portal veins (pedicles, selective hilar, suprahilar and intrahilar
      clamps), suprahepatic veins or vena cava; selectivity: partial or total clamp of
      hepatic blood supply; duration, continuous or intermittent; association measures
      to favor tolerance to ischemia (cooling, preservation fluid) or to limit
      downstream consequences (extracorporal circulation, derivation). The optimal
      clamp depends on the localization of the lesion and its relations with the great
      vessels, presence of liver disease, and the patient's general and cardiovascular
      status as well as the experience of the operator and the anesthesist. The goal is
      to use clamp as sparingly as possible, favoring selective clamps to avoid
      ischemia.

PMID- 12071019
TI  - [Surgical hand washing].
AB  - Hand washing is required to prevent nosocomial infection. We reviewed the
      literature, analyzing controlled randomized trials providing the best level of
      evidence. The different products and techniques evaluated in these trials are
      detailed. Compliance with hand washing protocols is also discussed.

PMID- 12071020
TI  - [Surgical treatment of total rectal prolapse with rectal fixation (Orr-Loygue
      technique)].

PMID- 12071021
TI  - [Shouldice].

PMID- 12071022
TI  - [Management of spermatic cord torsion].

PMID- 12071023
TI  - [Unusual spontaneous fistula].

PMID- 12071024
TI  - [Value of radiotherapy and chemotherapy in treatment of operable cancers of the
      esophagus].
AB  - Radiotherapy and chemotherapy have been used for more than twenty years as
      adjuvant treatment of operable cancer of the esophagus. The palliative effect of
      adjuvant (or neoadjuvant) radio- and/or chemotherapy has been demonstrated in
      numerous randomized trials. The purpose of this review is to present the
      principal randomized trials conducted in the treatment of operable cancer of the
      esophagus. Alone, radiotherapy does not significantly improve survival in
      patients with operable cancer of the esophagus, irrespective of the pre- or
      postoperative timing (three trials and one meta-analysis for preoperative, three
      trials for postoperative, and one trial for pre- and postoperative radiotherapy).
      Likewise, alone chemotherapy does not significantly improve survival whether
      given preoperatively (four trials), postoperatively (two trials) or pre- and
      postoperatively (one trial). Radiochemotherapy combinations appear to provide
      more hope, but preliminary results are insufficient to draw a clear conclusion.
      Nevertheless, trial comparing radiotherapy results with chemotherapy, conducted
      pre- or postoperatively (four trials) appear to demonstrate a significant effect
      of chemotherapy. The two trials using neoadjuvant therapy have been conducted on
      patients with adenocarcinomas of the cardia and/or the lower esophagus and have
      demonstrated very encouraging results for a small number of patients. Finally,
      the Herslovic trial, while conducted in patients who were initially inoperable,
      is the only one which has demonstrated superiority of radiochemotherapy over
      radiotherapy alone. In conclusion, there is still much room for improvement in
      survival using combined radio- and chemotherapy with different forms (new agents,
      new associations) and treatment modes (pre- and postoperative or postoperative
      alone). Despite the wide use of radiotherapy and chemotherapy for cancer of the
      esophagus, it must be recalled that surgical resection remains the method
      providing the best chances of survival.

PMID- 12071025
TI  - [Left lobectomy by laparoscopy].

PMID- 12071026
TI  - [Choledocho-duodenal anastomosis with celioscopy].

PMID- 12071027
TI  - [Mechanical digestive tract suture. 12: Circular anastomosis].

PMID- 12071028
TI  - [Retroperitoneal cystic lymphangioma].

PMID- 12071030
TI  - [Training of residents in surgery: need for contractual agreement].

PMID- 12071029
TI  - [57-year-old woman presenting with "nodules" of the liver].

PMID- 12071031
TI  - [Radiologic pneumoperitoneum without perforation of a hollow viscus].
AB  - About 10% of the radiological pneumoperitoneums occur without hollow viscus
      perforation. Pseudopneumoperitoneum is defined when the subphrenic lucency does
      not correspond to free intraperitoneal air: subphrenic fat pad, linear lung
      atelectasis, abnormal subphrenic shape, Chilaiditi syndrome or subphrenic
      abscess. True pneumoperitoneum without hollow viscus perforation may result from
      diffusion of thorax-derived air through a phrenic defect or along sheaths of
      mediastinal blood vessels. The female genital tract represents another route for
      intraperitoneal air penetration. Other etiologies include iatrogenic
      pneumoperitoneum (after abdominal surgery and digestive endoscopy) and
      pneumatosis cystoides intestinalis, when the subserous intraparietal gaseous
      bubbles rupture into the peritoneal cavity.

PMID- 12071032
TI  - [Is the non-university hospital a place for training residents in surgery?].

PMID- 12071033
TI  - [University and non-university hospital centers: residency in surgery needs
      both].

PMID- 12071034
TI  - [Congress of the American College of Surgeons. New Orleans, 7-12 October 2001].

PMID- 12071036
TI  - [Corticotherapy for asthma in the child].
AB  - Corticosteriods have a puissant anti-inflammatory action and enjoyment a central
      role in the treatment for childhood asthma. Systemic steroids are used in
      resistant bronchodilatator exacerbations of asthma. Usually steroids are given
      for short courses, rarely for long term in severe asthma with high risk of side
      effects. Inhaled corticosteroids have'nt changed the treatment for childhood
      asthma and are recommanded in persistent asthma. Inhaled steroids are well
      tolerant even at high doses, but it must always research the minimal effective
      dose. The aim of steroid's treatment is controlling asthma with minimal side
      effects to give a normal life to the asthmatic children.

PMID- 12071037
TI  - [Tunisian health profile: present state and trends].
AB  - We will try to value the Tunisian Health Profile, its present state and its
      tendencies. Data have been collected by various sources, in particular
      international and national organism. The total fertility rate passed from 8 in
      1966 to 2.01 in 1999. Besides a light ageing of the population is started (9% of
      the population are aged of more than 60 years in 1999). Death rates recorded a
      decrease, mainly of the infantile mortality (140%@1000 in 1966 against 24.7%@1000
      in 1999) and the maternal mortality (68.9 per 100,000 living births in 1994
      against 220 in 1980-1984). The life expectancy at birth passed from 51 years in
      1966 to 72.4 years in 1999. According the morbidity we attend the receding of the
      majority of transmitted diseases. Resources injected in the system of cares also
      evolved: The medical density passed from 1 per 6700 inhabitants in 1966 to 1 per
      1300 in 1999. Tunisia recorded the most elevated scores for the preventive
      activities in particular at the vaccinal coverage. The global evolution of the
      Tunisian health profile is marked by the epidemiological transition buy which
      pass the country currently. This phase is delicate because it's generating of a
      growth of care expenses. Decision-makers must be careful to consider advantage
      priorities and the profitability of the investments.

PMID- 12071038
TI  - [Esophagogastroduodenitis in the newborn. Report of 90 cases].
AB  - Oesophagogastroduodenitis (OGD) is a frequent situation in the newborn and run a
      benign course. Ninety cases of OGD were studied. Diagnosis was established by
      endoscopy. Presenting symptoms are dominated by gastrointestinal bleeding (70
      percent of cases). Oesophagitis and/or gastritis were observed in all cases,
      associated with duodenitis in 34.5 percent of cases. Evolution was good with
      complete recovery of the symptoms and healing of mucosal lesions in 74.4 percent
      of controlled patients. Pathogenesis of neonatal OGD remains undetermined.

PMID- 12071039
TI  - [Mortality in cirrhosis: prevalence, causes, and predictive factors].
AB  - To determine the global mortality rate during cirrhosis, to point out its
      principal causes and to look for factors associated with a higher death risk in
      cirrhotic patients. We carried out a retrospective study on patients hospitalized
      for cirrhosis during a seven-year period. We indicated the number of deceased
      patients, as well as the cause and the time interval for death. Age, sex, Child's
      score, etiology and the state of the cirrhosis were considered in a univariate
      and a multivariate analysis to look for mortality predictive factors. 109
      patients (49 males, 60 females) of average age 57 years (15-87) were studied. The
      average follow-up interval was 30 months (1-96). The global mortality rate was
      24%, with a five-year survival rate of 66%. In univariate analysis, mortality was
      more frequent in the following cases: presence of an initial complication (p <
      0.001), Child C cirrhosis (p = 0.02) and post-hepatitic B cirrhosis (p = 0.004).
      In multivariate analysis, only B viral etiology (five-year survival rate of 48%,
      p = 0.002) and the existence of an initial complication (five-year survival rate
      of 30%, p < 0.001) were independently associated with a higher mortality risk.
      Our study showed that cirrhosis is associated with an important mortality. Our
      results confirm the poor prognosis of a cirrhosis revealed by an inaugural
      complication and suggests that post-hepatitic B cirrhosis is more severe than
      post-hepatitic C cirrhosis.

PMID- 12071040
TI  - [Multidrug resistance in Klebsiella pneumoniae: multicenter study].
AB  - The extensive use of broad spectrum antibiotics, especially the third generation
      cephalosporins (C3G), was followed by the emergence of newer plasmid mediated
      betalactamases called extended spectrum betalactamases (ESBLs). To assess the
      impact of K. pneumoniae resistant to 3GC in Tunisia, this study was conducted in
      3 teaching hospitals. A total of 1110 strains of K pneumoniae was collected. The
      antibiotics susceptibilities were tested by diffusion method using Mueller-Hinton
      agar. The quality control was regularly performed. I ESBLs producing solates were
      detected using the double-disc synergy test. Data analysis was done using the
      Whonet 4 software. 23.6% K. pneumoniae isolates showed phenotype pattern of ESBLs
      producers. The double-disc synergy test was positive in 75% of the cases. These
      isolates were recovered from hospitalized patients in different wards but mainly
      from pediatrics (23.6%), medicine (23.2%), surgery (22.9%), intensive care units
      (11%) and neonatology (11%). 54% were isolated from urines, 22% from blood
      cultures. These isolates remained susceptible to imipenem (100%) and most of them
      to cefoxitin (96.4%) but all had associated resistance to aminoglycosides,
      quinolones and trimethoprim-sulfamethoxazole. The prevalence of multidrug
      resistant K. pneumoniae is high. This resistance can be minimized by the
      implementation of infection control measures including handwashing and isolation
      procedures.

PMID- 12071041
TI  - [Frequency of Pneumocystis carinii pneumonia in HIV-infected patients in
      Tunisia].
AB  - In Tunisia, as in most african countries, Pneumocystis carinii pneumonia (PCP) is
      considered to be rare in HIV-infected patients. Frequencies of 8.6% and 21% have
      been reported. We examined 27 broncho-alveolar lavage specimens collected from
      HIV-infected tunisian individuals with respiratory symptoms over 4 years (1994
      1997), by cyto centrifugation, Giemsa and Gomori-Grocott stain. Pneumocystis
      carinii (P carinii) was present in 9 cases, accounting for 33.3% of all
      specimens. Investigation of the reasons for the differences between african
      reports is necessary to establish appropriate therapeutic management. Technical
      difficulties of direct recognition of P carinii and selection bias may account
      for differences between african reports. However, differences still remain
      between the frequencies recorded in Africa and in other parts of the world, and
      recent advances seems to correlate this with geographical biodiversity of human
      derived strains of P carinii and with differences in host ethnic background.

PMID- 12071042
TI  - [Non-traumatic paraplegia at the campus teaching hospital of Lome. Report of 243
      cases].
AB  - To ascertain the aetiology, of non traumatic paraplegia retrospective survey,
      concerning 2396 patients hospitalised from January 1st 1995 to December 31st
      1999, was done. Two hundred forty three cases were founded after investigation.
      The frequency of non traumatic paraplegia was 10.14%. Peripheral motor neuron's
      causes were 48.97% (119 cases). In this group, tropical neuromyelopathies were
      the commonest 65.54% (78 cases) while Guillain Barre syndrome was 3.36% (4
      cases). Bones, epidural et meningeal (envelope) causes were 38.68% (94 cases). In
      this group, tuberculosis was 17 cases, tumour 36 cases. Central motor neuron
      causes were 9.46% (23 cases) with HIV myelitis 13 cases, tumour 3 cases,
      degenerative conditions 6 cases. It is concluded that the major causes of non
      traumatic paraplegia in Lome are similar to that reported from sub sahara
      countries with tropical neuromyelopathies, tumours, tuberculosis and HIV
      myelitis.

PMID- 12071043
TI  - [Actinomycosis: report of 21 cases. Experience of the Anatomy and Cytopathologic
      Pathology Laboratory of the Rabta Hospital].
AB  - Actinomycosis is a chronic suppurative granulomatous disease caused by an
      anaerobic Gram positive germ, Actinomyces. From 1994 to 1999, 21 cases of
      actinomycosis have been diagnosed in our laboratory. The main localisations were
      cervicofacial and gynecologic the diagnosis relies on histopathologic examination
      that shows actinomycosic granules.

PMID- 12071045
TI  - [Treatment of inguinal hernia under local anesthesia at the Central University
      Hospital of Lome].
AB  - In our search study, we were allowed to do 74 operations of inguinal hernia (71
      indirect and 3 femoral hernia). All these patients were operated under local
      anaesthesia with zylocaine 2%. The dose was between 4 to 40 ml. After surgery,
      the patients were hospitalised for different times beginning from 3 hours up to
      28 days. The post operative care was done in the out clinics. 53 of our patients
      left in the same day of the operation (71.62%); 3 the second day of the operation
      (4.05%); 7 after 72 hours (9.45%). Eleven patients were afraid and refused to
      leave there beds using some medical causes (14.86%). The for home of some
      patients was also the cause of passing long time in the hospital. No surgied
      complications were detected. The single death registered in our serie was not due
      to this method of anaesthesia. It was a hypertensive patient with severe cardiac
      insufficiency refused by general anaesthesia. Not single anomaly was noticed by
      the monitor during operation, also the electrocardiogram didn't change during
      injection. The death was on the 3rd day post-operative and was bind to the
      previous cardiac condition of the patient (autopsy was not practical). We must
      put in mind this line of treatment which minimises complications for the
      resolution of insufficient materials and instruments.

PMID- 12071044
TI  - [Mycosis fungoides. Study of a series of 11 Tunisian cases].
AB  - Mycosis fungoides is an epidermotropic cutaneous T lymphoma. It's a non
      Hodgkinian lymphoma. We report the results of a retrospective review of 11
      mycosis fungoide seen during 22 years. The frequency of MF was about 39.3% among
      all cutaneous lymphoma. Six patients were male and 5 were female; the mean age
      was about 56 years. Mean delay between diagnostic and the first manifestation was
      about 25 months. All patients had the progressive form: 4 had infiltrate plaques
      and 7 were at the tumoral phase. Lymph nodes and medullar metastases were noted
      respectively in 1 and 2 cases. Treatment was mono or polychemotherapy associated
      in 6 cases with topical drug. Three patients died of their diseases According to
      our experience and after reviewed the literature, we notice that our patients are
      slightly younger without male predominance. The diagnostic was done tardily and
      this may explain the pejorative prognostic.

PMID- 12071046
TI  - [Uterine rupture: report of 41 cases].
AB  - To establish the epidemiological profile, of patients who presented a uterine
      rupture, as well as the obstetrical follow up, the neonatal outcome and the
      prognosis factors. A retrospective study of 41 cases of uterine rupture treated
      in the maternity center of Tunis during a 5-year period. The frequency of uterine
      rupture was 1.38%@1000 of births. Rupture in scarred uterus was found in 58.5% of
      the cases against 41.5% in sain uterus. Three risk factors were statistically
      significant in our series: cesarian section, multiparity and high fetal weight.
      Uterine rupture is a medico-surgical emergency causing materno-fetal morbidity
      and mortality.

PMID- 12071047
TI  - [Struma ovarii. Report of a malignant and a benign case].
AB  - Struma ovarii is a rare type of ovarian teratoma, composed entirely or in part of
      thyroid tissue. Malignant Struma ovarii were exceptional. We report one benign
      and one malignant cases of Struma ovarii. We insist upon their rarety and the
      difficulty of preoperatory diagnosis. Prognosis is good after surgery.

PMID- 12071048
TI  - [Quality of life in oncology].
AB  - The measure of the quality of life in cancerology appears more and more as a
      fundamental criteria in the evaluation of therapeutic results. The study of the
      quality of life obeys three types of aims: descriptive, correlational and
      explanatory, and therapeutic. For evaluation, scales for quality of life were
      introduced, these scales use a quotation technique with the help of
      questionnaires or linear analog self assessment. Questionnaires represent the
      mostly used method. They are composed of several questions or items having
      predetermined answers for which the patient should check or circle the choice
      corresponding best to his state. To be useable, a questionnaire must satisfy
      certain criteria of quality: reliability, validity and sensitivity. In spite of
      the remarkable progress during recent years in the evaluation of the quality of
      cancerous patient life, there still exists some conceptual and practical problems
      that are not yet solved.

PMID- 12071049
TI  - [Effect of thermal acclimation on the expression of gene coding for lactate
      dehydrogenase A4 in loach skeletal muscle].
AB  - Acclimation of Misgurnus fossilis to 5 and 18 degrees C induced considerable
      changes in LDH-A gene expression in white skeletal muscle. Qualities of total and
      messenger RNA isolated from weighted portions of muscle are considerably higher
      after acclimation to 18 degrees C as compared to 5 degrees C. However, a PCR
      assay of cDNA synthesized from these mRNA and equalized by optical density
      demonstrated that the level of LDH-A gene expression was indistinguishable for
      high and low acclimation temperatures, while expression of other genes
      (glyceraldehyde-3-phosphate dehydrogenase and alpha-actin) considerably increased
      at 18 degrees C as compared to 5 degrees C. The specific enzymatic activity of
      LDH from white skeletal muscle of the fish acclimated to low temperature is by
      20% higher than that for high-temperature acclimation. Structural analysis of the
      PCR products synthesized on cDNA-5 degrees C and cDNA-18 degrees C has revealed
      no differences. However, there are indirect indications of the differences in the
      C-thermal region of the LDH-A molecule. Northern hybridization reveals the
      differences at the RNA level: one (1400 bp) or two (about 1600 and 1400 bp)
      hybridization signals have been found in mRNA-5 degrees C and mRNA-18 degrees C,
      respectively. The presence of two fractions in the mRNA-18 degrees C indicates
      alternative splicing.

PMID- 12071050
TI  - [Antimicrobial activity of myeloperoxidase from neutrophil peroxisome].
AB  - Myeloperoxidase plays the key role in antimicrobial oxygen-dependent activity of
      neutrophils. This heme-containing enzyme catalyzes HOCl formation from H2O2 and
      Cl-. HOCl is a strong oxidation agent produced at the significant level by
      neutrophils. Myeloperoxidase easily oxidizes thiocyanate to hypothiocyanate and
      Br- to HOBr, which are involved in protective reactions. Myeloperoxidase reacts
      quickly with nitric oxide and peroxynitrite in inflammation foci. All these
      reactions affect neutrophil-induced oxidative stress.

PMID- 12071051
TI  - [Changes in macro- and micro element composition in the organs of irradiated
      animals].
AB  - We studied the content of Al, Cd, Co, Cu, Fe, Mg, Mn, P, Pb, S, and Zn in the
      liver, kidneys, lungs, and spleen of mice with total radiation dose of 7.5 Gy
      using atomic emission spectral analysis with an inductively coupled argon plasma.
      The qualitative content of macro- and microelements and coordination between
      their concentrations statistically determined from coefficients of linear
      correlation differ between the tissues of the irradiated and control animals.
      Radiation damage decreases phosphorus content in all studied organisms and is a
      marker of disturbed conjugated oxidative phosphorylation. The most significant
      radiation-induced disturbance of macro- and microelement balance was detected in
      the spleen; it features decreased content of phosphorus, magnesium, and cobalt,
      as well as increased content of zinc and aluminum and considerably increased iron
      content. The revealed macro- and microelements disbalance in spleen, liver,
      kidneys, and lungs can be considered as a test for primary biological response to
      radiation damage.

PMID- 12071052
TI  - [Responses of Seidlitzia rosmarinus to salt stress].
AB  - The responses of the salt-accumulating halophyte Seidlitzia rosmarinus to salt
      stress (500 mM NaCI) were studied. Observations were carried out over the span of
      72 h. Three phases of responses were identified. Parallel observations of
      physiological parameters and cell ultrastructure allowed us to conclude that S.
      rosmarinus is capable of resisting salt stress owing to changes in its
      osmoregulatory systems (ions or organic osmolytes). In addition, these
      observations showed that salt ions are localized in the central vacuole of leaf
      cells (via pinocytosis) and also in small cytoplasmic vacuoles of leaf and root
      cells.

PMID- 12071053
TI  - [Contradictions in modern data on the structure and function of dog hepatoid
      circumanal glands].
AB  - Since the 1950s, an erroneous viewpoint has gained a foothold in the special and
      reference literature that dog hepatoid circumanal glands have an abortive nature,
      lack efferent ducts, and show no signs of secretory activity. Nevertheless, most
      modern researchers indicate that these glands are actively functioning structures
      differentiated to exercise some function according to their histological pattern;
      however, no one has managed to define this function. The latest international
      publication (Atoji et al., 1998) considers dog circumanal hepatoid glands as a
      "circumanal body" similar to epidermis rather than glands. We discuss strong and
      weak points of the data on dogs hepatoid circumanal glands published in 1950s
      1990s in comparison with those obtained in our purposeful long-term investigation
      of various hepatoid glands. We strongly disagree with the viewpoint of Atoji et
      al. (1998); hepatoid circumanal glands of dog and other canids should be
      considered as odor glands, their abundant protein secretion covers the skin
      surface in the circumanal region, it is preserved on fecal marks, and its smell
      is perceived during mutual nosing of the anal region.

PMID- 12071054
TI  - [Architectonic and diagnostic significance of hair cuticle].
AB  - Guard hair and spine architectonic were studied in 345 mammalian species using
      scanning electron microscopy. Comparative morphological analysis of the author's
      and published data was performed to systematize the available information.
      Original terminology and classification of the main hair cuticle patterns have
      been proposed. The hair cuticle structure patterns, their adaptability, and value
      for taxon identification are discussed.

PMID- 12071056
TI  - [On temporal dynamics of morphological variations in the Black sea mussel Mytilus
      galloprovincialis lam].
AB  - Temporal variations in morphological characters of the shells were studied in 12
      samples of mussels M. galloprovincialis Lam. from the Black Sea commercial
      collectors that belong to different generations. The samples were shown to be
      diverse in every studied character and the degree of characters' variability in
      the samples was different. The morphological diversity of samples diminished with
      age. Different generations from the same habitat had specific features of age
      related variability expressed as different rates of age-related changes and
      direction and degree of variability. This effect is considered as an index of the
      influence of ecological conditions on the shell growth and formation.

PMID- 12071055
TI  - [Acoustic analysis of signals in mammals].
AB  - Spectral-prosodic characteristics of signals were analyzed synchronously with the
      main frequency for 32 mammals and one reptile using a KAZ-01 complex sound
      analyzer. The method of phoneme analysis was adapted for analysis of the signals.
      The main features of signaling in mammals have been revealed, which differed from
      those in birds and humans: low frequency range, low fundamental frequency, small
      number of local maxima, small frequency distance between them, and a significant
      amount of local maxima with zero energy.

PMID- 12071057
TI  - [Physiological and biochemical adaptations to respiration of hemoglobin
      containing hydrobionts].
AB  - Hemoglobin content in hemolymph of mollusks, crustaceans, and insect larvae, as
      well as in polychaete blood, is analyzed in the context of their respiratory
      conditions. The total supply of hydrobionts with respiratory pigment, as well as
      buffer capacity of hemolymph under normal and unfavorable conditions, is
      comparatively evaluated. The functions and properties of invertebrate hemoglobins
      are discussed.

PMID- 12071058
TI  - [Effect of dermorphin analogs on thermoregulation of rats under various thermal
      conditions].
AB  - We studied the influence of dermorphin (dermorphin) analogs with stereochemical
      modification of the amino acid residue proline in position 6 (Pro6), Tyr-D-Ala
      Phe-Gly-Tyr-Hyp-Ser-NH2, Tyr-D-Ala-Phe-Gly-Tyr-[D-Pro]-Ser-NH2, Tyr-D-Ala-Phe-Gly
      Tyr-[dehydro-Pro]-Ser-NH2, and Tyr-D-Ala-Phe-Gly-Tyr-[D-dehydro-Pro]-Ser-NH2,
      after their intraperitoneal injection at 0.5 mg/kg dose in the cold (4-7 degrees
      C), thermoneutral (27-28 degrees C), and hot (31-33 degrees C) environment.
      Stereochemical modifications of amino acid residue Pro6 proved to induce specific
      changes in the thermoregulatory effect of the peptide. Substitution of DPro6 for
      Pro6 has the most dramatic consequences: it considerably attenuates the
      thermoregulatory effect of dermorphin in the cold environment, cancels it in the
      hot environment, and inverts the dermorphin-specific thermoregulatory response in
      thermoneutral conditions. The data obtained indicate the important role of Pro6
      residue in realization of this physiological activity of dermorphins.

PMID- 12071060
TI  - [Heterogeneity and polymorphism of functionally specialized blood proteins in
      migratory fish: case study of the North Caspian population of the Russian
      sturgeon during sea and river periods of life. 1. Albumins].
AB  - A comparative study of the levels of heterogeneity and polymorphism of albumins,
      the most important functionally specialized blood proteins, has been carried out.
      The albumin system of Russian sturgeon undergoes distinct changes while the fish
      change habitat during the spawning migration from sea to river. They are
      expressed as an increased level of heterogeneity, an increased content of serum
      albumins in fish during the river period of life as compared to the sea period,
      and an increased share of a slow component of albuminograms. These changes
      suggest a significant role of the blood albumin system in adaptation of the
      Caspian sturgeon migratory species to fresh water life conditions.

PMID- 12071059
TI  - [Photosynthesis and oxygenation of the earth's atmosphere].
AB  - Based on the contemporary data concerning photosynthesis as a global
      biogeochemical mechanism of solar energy utilization and organic matter and
      oxygen production, the formation of photosynthesis in the Proterozoic is
      considered, as well as its role in transformation of the pre-Proterozoic oceanic
      hydrosphere and the Earth's atmosphere from a reduced to an oxidized state.
      Photosynthesis is considered the longest stage of organic world evolution. The
      problem of production of "excessive" oxygen is considered, which entered and is
      entering the atmosphere through the oceanic hydrosphere and determines the
      process of its organization.

PMID- 12071061
TI  - [Changes in the spatial structure of the destruction process under the conditions
      of atmospheric pollution of forest ecosystems].
AB  - Contamination of the southern taiga forests (Middle Urals) by discharges from
      cooper smelters (heavy metals combined with SO2) not only decreases the mean rate
      of decomposition of pure cellulose, but also radically changes the spatial
      structure of the destruction process. Heterogeneity of distribution of the
      destruction rate is sharply increased near the source of discharge due to
      differentiation of the space into microregions with high and low destruction
      rates. The characteristic size of spatial heterogeneity amounts to several tens
      of centimeters and the distribution of microregions with a high rate is
      accidental within several tens of meters. A hypothesis has been put forward that
      the described changes in the spatial structure of the destruction process are
      related, above all, to disturbed colonization of the substrate by soil
      myxomycetes.

PMID- 12071062
TI  - [ATP content in cryopreserved sperm of Siberian white cranes Grus leucogeranus
      (Aves: Gruiformes)].
AB  - ATP contents were studied in the native and cryoconserved sperm of Siberian white
      cranes Grus leucogeranus using bioluminescence analysis. The ATP content in
      freshly obtained spermatozoa was 12.7 nmol/10(8) cells. No ATP was found in the
      seminal plasma. In the process of freezing-thawing, the ATP concentration in the
      spermatozoa decreased by 30%. The differences in the dynamics of ATP content
      during cryoconservation of sperm of white cranes and other birds and mammals are
      discussed.

PMID- 12071063
TI  - Clinico-pathological features of breast cancer in Pakistan.
AB  - OBJECTIVE: To obtain information about presenting features of women with breast
      cancer in Pakistan, to compare these data with information on patients with
      breast cancer in the United States and to highlight the differences. METHODS:
      Patients referred to the National Cancer Institute, Karachi, Pakistan between
      January 1, 1994 and February 28, 1999 who had been recently diagnosed with breast
      cancer were prospectively evaluated. A printed questionnaire was used as an
      interview guide. Information was obtained about demographic features/clinical
      characteristics, stage of the disease and previous therapy. RESULTS: Five-hundred
      sixty-six patients were evaluated. Mean age was 47.7 +/- 11.8 years. Risk factors
      for breast cancer were observed in a minority. Mean number of pregnancies was
      4.4. Eighteen percent had positive family history mostly in first-degree (64%)
      relatives. The vast majority (93%) discovered the lump accidentally. Average size
      was 5.7 +/- 2.3 cm. Over half had used unconventional therapies before receiving
      standard medical care. Most patients had undergone modified radical mastectomy
      and only 5% had conservative surgery done. Almost one third had locally-advanced
      disease. Seventeen percent had metastases at the time of diagnosis. CONCLUSION:
      Despite significant advances made in cancer care in the United States, patients
      in Pakistan still present at an advanced stage. Antecedent use of unconventional
      therapies before seeking any medical advice is widespread. There is a great need
      for public education to enhance awareness about cancer and other health habits.

PMID- 12071064
TI  - Epidermal growth factor receptor (EGFR) as a prognostic marker: an
      immunohistochemical study on 315 consecutive breast carcinoma patients.
AB  - OBJECTIVE: To assess the independent and interdependent prognostic value of
      epidermal growth factor receptor (EGFR) in carcinoma of breast in female
      population. The Type 1 family of growth factor receptors includes epidermal
      growth factor receptor (EGFR also known as EGFR1). METHODS: The expression of
      EGFR protein was analysed immunohistochemically on 315 tumour specimens of
      infiltrating ductal carcinoma of breast. These patients also had axillary lymph
      nodes sampling. RESULTS: Overexpression and/or amplification of EGFR was observed
      in 70 (22.00%) tumours. Eleven (16%) were grade I, 43 (61%) grade II and 16 (23%)
      grade III tumours. Axillary lymph node metastasis had significant correlation
      with intensified positivity of EGFR (p < 0.05). Significant number of EGFR
      positive patients developed local recurrence and distant metastases to brain,
      liver and bone (p < 0.05). EGFR positivity showed significant correlation with
      the disease free and overall survival (p < 0.05). At a median follow-up of 48 (4
      years) months in EGFR positive patients, the overall survival was 3.39 years and
      disease free survival was 2.86 years. EGFR negative tumour patients showed a
      better survival. In this group the overall survival was 4.62 years and the
      disease free survival was 4 years. CONCLUSION: EGFR analysis can be a useful
      indicator for the selection of patients who are at the high risk, for hormonal
      therapy decisions and can be useful as a target for new treatment modalities.

PMID- 12071065
TI  - Predictors of mortality in brain abscess.
AB  - OBJECTIVE: Brain abscess carries significant morbidity and mortality. Our
      objective was to elucidate the clinical presentation of brain abscess and to
      assess predictors of mortality in these patients. METHODS: All patients with a
      brain abscess presenting to the Aga Khan University Hospital, a tertiary care
      referral center in Karachi, Pakistan, were studied retrospectively. Statistical
      analysis involved univariate analysis and a logistic regression model. RESULTS:
      Among the 66 patients analyzed, a distant metastatic focus of infection was the
      most commonly identified predisposing factor (29%). Otogenic infection was the
      commonest contiguous source and sinusitis was noticeably absent. Multiple
      abscesses were frequent (35%). Streptococci were the most common isolates (39%).
      Lumbar puncture was performed in 44% and steroids administered in 33%. Treatment
      was surgical in 58%. Most comatose patients were treated conservatively. Overall
      mortality was 29%. Univariate analysis identified comatose presentation and
      identification of a distant focus of infection as predictors of mortality. The
      logistic regression model, however, identified a distant focus of infection as
      the only independent predictor. CONCLUSION: Age greater than 30 years,
      corticosteroid use, multiple abscesses, performance of lumbar puncture and
      conservative management had no affect on outcome.

PMID- 12071066
TI  - All seizures are not epilepsy: many have a cardiovascular cause.
AB  - OBJECTIVES: The aim of this study was to investigate the value of cardiovascular
      tests to diagnose convulsive syncope in children with apparent treatment
      resistant epilepsy and to assess the extent of misdiagnosis of epilepsy in
      children. BACKGROUND: Adult studies have shown that up to 35% of epileptics may
      have been misdiagnosed. These patients may have cardiovascular syncope, with
      abnormal movements due to cerebral hypoxia, which may be difficult to
      differentiate from epilepsy. Studies in children are lacking. METHODS: Thirty-one
      children (12 male, mean age 10.07 +/- 5 years [range 4 to 17]) who were
      previously diagnosed with epilepsy were studied. Inclusion criteria were
      continued attacks despite adequate anticonvulsant drug treatment (n = 17) or
      possible epilepsy on the basis of clinical grounds (n = 14). Each patient
      underwent a 12-lead electrocardiogram (ECG), an orthostatic test and carotid
      sinus massage during continuous ECG and blood pressure monitoring. Ten patients
      had Holter monitoring. RESULTS: An alternative diagnosis was found in 19 patients
      (61.3%), including 8 (47%) of 17 patients taking anticonvulsant medications. Nine
      patients (29%) developed profound hypotension or bradycardia during orthostatic
      test, confirming the diagnosis of vasovagal syncope. Seven patients (22.5%) had
      long Q-T syndrome (LQTS). Two (6.4%) had significant ECG pauses during carotid
      sinus massage. In these two patients episodes of prolonged bradycardia correlated
      precisely with seizures by Holter recording, was noted. One patient (3.2%)
      developed psychogenic symptoms during the orthostatic test. CONCLUSION: A simple,
      non-invasive cardiovascular evaluation may identify an alternative diagnosis in
      many children with apparent epilepsy and should be considered early in the
      management of children with convulsive episodes.

PMID- 12071067
TI  - Utilising field assignments in survey methodology course at Ziauddin Medical
      University, Karachi.
AB  - OBJECTIVE: To describe the teaching-learning strategy employed in the module of
      Survey Methodology for undergraduate medical students at Ziauddin Medical
      University. SETTING: Medical students of Ziauddin Medical University, Clifton,
      Karachi. METHODS: The objectives of the Survey Methodology course were developed
      so that a student would be able to design and conduct a small survey
      independently. For this purpose the students were required to participate in a
      census survey of a squatter settlement. The questionnaire for the survey was
      developed with the students, which included the demographic information of the
      households. It was discussed and pretested with the medical students. The
      students edited and entered the data on computer using Epi-Info. They were
      trained in sampling methods, data collection, data editing and entry through
      lectures and small group sessions. At the end of the course, students filled the
      course evaluation form. RESULTS: Out of 117 students who responded, 63% found the
      course to be useful. Small group sessions were regarded as the most helpful
      teaching strategy by 91% of the students. Majority (74%) of the students
      recommended that field visits should be a part of teaching strategy. CONCLUSION:
      The Survey Methodology course reinforces the importance and practical application
      of research methods. The students appreciate the course especially the small
      group sessions and the field visits.

PMID- 12071068
TI  - Therapeutic re-appraisal of multiple drug resistant Salmonella typhi (MDRST) in
      Pakistani children.
AB  - BACKGROUND: The emergence of multi drug-resistant Salmonella typhi (MDRST) in
      many developing countries including Pakistan, has led to a search for suitable
      alternatives to conventional therapy. Quinolones have been found to be an
      effective alternative for the treatment of MDRST, in adults as well as in
      children. METHODS: The efficacy of various therapeutic regimens currently used
      for the treatment of Typhoid was analysed. Children 1 month to 12 years of age
      admitted to the Children's Hospital from 1990 to 1993 with fever and Salmonella
      typhi isolated from blood cultures were included in this retrospective analysis.
      RESULTS: The cumulative prevalence of Multiple Drug Resistant Salmonella typhi
      (MDRST) was 67.2%. Only 32.8% of isolated Salmonella typhi were susceptible to
      chloramphenicol and amoxicillin. The cumulative cure rate with conventional
      therapy (chloramphenicol or amoxicillin) was 47.4% and 53.6% children needed a
      change of therapy. The average hospital stay for the non-responders to
      conventional therapy was 9.2 days as compared to 7.7 days for the responders. The
      average hospital stay of the patients treated with a third generation
      cephalosporin was 12.7 days. Patients treated with ofloxacin, a flouroquinolone
      drug, did not need a change of therapy. The average hospital stay of the patients
      treated with flouroquinolones was 6.2 days. CONCLUSION: There was a high
      prevalence of multiple drug resistant typhoid fever in hospitalized children,
      leading to a high failure rate with conventional therapy. This resulted in
      frequent change of therapy, delayed defervesence and prolonged hospital stay. The
      flouroquinolones were found to be the most effective drug against MDRST.

PMID- 12071070
TI  - Palliative medicine: an emerging discipline.

PMID- 12071069
TI  - Efficacy of CHO cell derived hepatitis B vaccine in children and adults.

PMID- 12071072
TI  - View box case--3. Hepatic hemangioma.

PMID- 12071071
TI  - Mucosa associated lymphoid tissue lymphoma (Maltoma) in patients with cold nodule
      thyroid.

PMID- 12071073
TI  - The effect of simvastatin on diabetic dyslipidemia.

PMID- 12071074
TI  - The need for new hepatitis B vaccines.

PMID- 12071075
TI  - Prevalence of HIV, hepatitis B and C amongst health workers of Civil Hospital
      Karachi.
AB  - OBJECTIVE: To determine the prevalence of HIV, Hepatitis B (HBV) and Hepatitis C
      (HCV) amongst the health workers of Civil Hospital Karachi (CHK). MATERIAL AND
      METHODS: Prospective study. A precoded Proforma was filled out which included
      questions regarding the knowledge, attitude and practices (KAP) of HIV, HBV and
      HCV. SETTING: Departments of a tertiary health care facility at CHK. Antibodies
      to HIV, HCV and Hepatitis B surface antigen (HBsAg) were done using enzymes
      linked immunabsorbant assay [ELISA]. RESULTS: Uptake of screening was 98% to
      those offered. The prevalence was 5-6% for antibodies to HCV, 2.4% for HBsAg,
      while none of those studied had antibodies to HIV. CONCLUSION: Our results show
      the prevalence of antibodies to HCV in health workers are 20 folds higher than
      health workers in the developed countries. Similarly, the prevalence of HBV
      although not as high as HCV is significant. Seroprevalence of HIV does not exist
      in this group. We need to ensure better training; regulations regarding
      preventive and safety measures also need to be enforced.

PMID- 12071076
TI  - Health sector reform in Pakistan: why is it needed?
AB  - OBJECTIVE: The health care system in Pakistan is beset with numerous problems-
      structural fragmentation, gender insensitivity, resource scarcity, inefficiency
      and lack of accessibility and utilization. Moreover, Pakistan is faced with a
      precarious economic situation, burdened by heavy external debt and faltering
      productivity and growing poverty. These circumstances, on the one hand,
      underscore the need for innovative health sector reform and, on the other,
      indicate the complexity of the task involved. The recently announced Devolution
      Plan of the Government of Pakistan (GOP) that seeks to introduce elected district
      level local bodies, offers an opportunity to assess the existing publicly funded
      health care system and introduce far-reaching reforms to make it more efficient
      and effective. STUDY DESIGN: Based on a critical analysis of secondary data from
      the public domain as well as from various research projects undertaken by the Aga
      Khan University, the paper intends to present convincing arguments for
      fundamental health sector reform in Pakistan. PRINCIPLE CONCLUSIONS: (a) All
      factors point to the need for a fundamental reform of the health sector in
      Pakistan; and (b) the Devolution Plan presents an unique opportunity that must be
      seized to reshape the health care system and make it more efficient and
      effective.

PMID- 12071077
TI  - [Your ultrasound diagnosis? Acute colitis, most likely of infectious etiology].

PMID- 12071078
TI  - [Helicobacter pylori--2002].
AB  - Treatment recommendations for H. pylori infection are peptic ulcer disease, MALT
      lymphoma, atrophic gastritis and following gastric cancer resection as well as
      first degree relatives of gastric cancer patients. Advisable situations are
      functional dyspepsia, before introduction of NSAID's or intended long-term proton
      pump inhibitor treatment. It is thought that eradication therapy is not
      associated with gastro-esophageal reflux disease and does not enhance NSAID
      induced peptic ulcer healing. Therapy should be given as a package which
      considers first and second line eradication therapies together; in uncomplicated
      duodenal ulcer patients, eradication therapy does not need to be followed by
      further antisecretory treatment. First line therapy should be with triple therapy
      using a proton pump inhibitor (PPI), combined with clarithromycin and
      amoxycilline or metronidazole. Second-line therapy should use a quadruple therapy
      with a PPI, bismuth, metronidazole and tetracycline. Where bismuth is not
      available, second line therapy should be with a PPI triple therapy. If second
      line quadruple therapy fails in primary care, patients should be referred to the
      specialist and handled on a case by case basis. Successful eradication should
      always be confirmed by urea breath test (UBT), or endoscopy-based tests if
      endoscopy is clinically indicated. Stool antigen test is the alternative if UBT
      is not available. A 'test and treat' approach based on non-invasive testing can
      be offered to adult patients presenting in primary care with persistent dyspepsia
      under the age of 45 years (the age cut-off may vary locally), having excluded
      those with predominantly gastroesophageal reflux disease (GERD) symptoms, NSAID
      users, and patients with alarm symptoms.

PMID- 12071079
TI  - [Diagnosis of gastroesophageal reflux].
AB  - Around 10-20% of the population suffer from the hallmark symptoms of heartburn,
      regurgitation, sour burping and retrosternal pain. Based on their characteristic
      medical history alone, such patients can usually be presumed to have
      gastroesophageal reflux disease (GERD). In around 30-50% of them, the endoscopic
      examination will reveal the typical erosions and ulcerations in the esophagus. In
      addition to the clinical symptoms, endoscopy plays a central role in diagnosing
      GERD. An endoscopy is always indicated whenever these warnings symptoms are
      present. In patients with persistent reflux problems, endoscopy is indicated to
      diagnose erosive reflux esophagitis. This procedure should include a routine
      biopsy taken distal to the Z-line to enable histological detection of the
      metaplasia associated with Barrett's esophagus. Although the majority of patients
      exhibit the classical symptoms and respond to acid suppression therapy, endoscopy
      may not find erosions (non-erosive reflux disease NERD). In these cases, further
      diagnostic steps must be taken to verify the diagnosis of gastroesophageal reflux
      disease. There are patients, moreover, who exhibit unclear, uncharacteristic
      reflux symptoms, such as respiratory diseases with bronchial asthma, chronic
      bronchitis, chronic cough or ENT problems like posterior laryngitis and globus
      sensation (a lump in the throat). In these uncertain cases and in patients with
      NERD, 24-hour pH monitoring can verify and objectify and acid gastroesophageal
      reflux. An association can then be made between acid reflux and symptomatology.
      As an alternative, trial therapy with a proton pump inhibitor can help identify
      patients who have acid-related problems and symptoms. Other functional tests such
      as radiographic examination, manometry or scintigraphy are less well suited, if
      at all, for primary diagnostics of gastroesophageal reflux disease.

PMID- 12071080
TI  - [Reflux disease: conservative therapy].
AB  - Gastroesophageal reflux disease--one of the most common gastroenterological
      disorders--is characterized by reflux symptoms (occasionally respiratory symptoms
      or laryngeal complaints) and/or mucosal lesions. Improvement of symptoms and thus
      of the quality of life, prevention of relapse and of complications are the most
      important aims of short and long term treatment. Proton pump inhibitors are
      superior to histamine receptor antagonists and are the treatment of choice.
      Relapses occur in about 75% of patients within one year after stopping of acute
      treatment. The treatment strategy depends on the severity of symptoms and
      esophageal lesions. Patients with mild esophagitis or endoscopic negative disease
      can be treated with proton pump inhibitors on demand. In severe and complicated
      cases, the uninterrupted long-term use of proton pump inhibitors is indicated. In
      these cases laparoscopic fundoplication could be a possible--albeit problematic-
      alternative. New endoscopic interventional therapies should only be used in
      controlled studies. Their role in the treatment of GERD will only be known in a
      few years when adequately controlled long term studies will be available.

PMID- 12071081
TI  - [Surgical therapy of gastroesophageal reflux].

PMID- 12071083
TI  - [Speech recognition in clinical routine, a pilot trial at the Zurich University
      Hospital].
AB  - Two systems for continuous German speech recognition were evaluated in pilot
      installations in a Department of Medicine. Word recognition accuracies of 92-94%
      were achieved one month after implementation. For standardized text the
      performance increased to 97%. Speech recognition proved to be economical for
      physicians when producing short reports, whereas for comprehensive discharge
      summaries no significant time savings were observed. All reports could be made
      available much faster by using speech recognition. However, some particle
      difficulties may still limit the success of comprehensive installations in
      clinical settings. Adequate hardware, appropriate choice of areas of application,
      reasonably quiet working conditions and well motivated users are essential for
      successful implementations.

PMID- 12071082
TI  - [Gastroesophageal reflux].

PMID- 12071084
TI  - [Medicamentous kidney protection in type 2 diabetic patients--is cheaper also
      more economical? A model calculation for Swiss health care].
AB  - Impaired renal function occurs in about 50% of patients suffering from type 2
      diabetes, and diabetic nephropathy has become the leading cause of endstage renal
      disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the
      most effective way to slow progression of diabetic nephropathy. Recent meta
      analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non
      dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective
      effects which go beyond the effect of blood pressure reduction. This has lately
      been confirmed by a prospective trial in comparison to the betablocker atenolol.
      Based on these data, demographics of the Swiss population, literature data on
      mortality rates of type 2 diabetics with impaired renal function and studies on
      true costs of antihypertensives, we calculated the costs of a longterm
      intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients
      with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was
      based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the
      betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas
      faster loss of renal function over time increased mortality rate and thus reduced
      the number of patients to be treated. Nevertheless, due to the fact that patients
      reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with
      costs of 316 millions of Swiss francs turned out to be much more expensive than
      the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss
      francs, respectively. Thus, low acquisition cost is not necessarily the only
      important determinant of overall costs of drug therapy.

PMID- 12071086
TI  - [Fatigue, weight loss and decline in general health in a young patient. Addison
      disease].

PMID- 12071085
TI  - [Molecular structure of human chorionic gonadotropin: new functions in
      immunology, endocrinology and oncology].

PMID- 12071087
TI  - [Bright disease: the first kidney disease].

PMID- 12071088
TI  - [What is your diagnosis? Bilateral sacroiliac gap phenomenon confirmed by CT
      scan].

PMID- 12071089
TI  - [Barrett esophagus--esophageal carcinoma: diagnosis].
AB  - The Barrett esophagus as the premalignent lesion for adenocarcinoma of the
      esophagus and the esophagogastric junction is of widespread interest. Endoscopy
      and histology are the diagnostic basis. Methylen blue staining and high
      resolution endoscopes facilitate the diagnosis of Barrett esophagus. Use of a
      high resolution endoluminal ultrasound probe and optical coherence tomography are
      new methods for evaluating the local depth invasion of the Barrett mucosa.
      Accurate pretherapy staging for esophageal carcinoma is important for a stage-
      directed therapy. After endoscopy and histology the endoscopic ultrasound is the
      method of choice for local regional staging of esophageal carcinoma. Computed
      tomography and positron emission tomography were shown to be especially useful in
      detection of distant metastases.

PMID- 12071091
TI  - [Barrett esophagus--esophageal carcinoma: surgical therapy].
AB  - Barrett's oesophagus is an acquired condition that occurs as a consequence of
      gastrooesophageal reflux. Continuous exposure of the Barrett's epithelium to
      gastric juice may lead from a low-grade to a high-grade dysplasia and
      subsequently to an invasive adenocarcinoma. Therefore, the first goal of
      treatment for patients with Barrett's oesophagus is the prevention of reflux to
      eliminate the risk of a progression to dyplasia and cancer. In contrast to
      medical treatment antireflux surgery restores the low oesophageal sphincter,
      abolishes reflux of gastric contents into the oesophagus and ends the repetitive
      injury to both the metaplastic and normal oesophageal mucosa. In case of
      Barrett's carcinoma of the distal oesophagus a radical transhiatal oesophagectomy
      with systematic abdominal and mediastinal lymph node dissection is the procedure
      of choice. After forming a gastric tube the reconstruction is done by a
      transposition of stomach through the posterior mediastinum and a cervical
      anastomosis. Because of substantial complications and long-term side effects the
      need for extensive resection in patients with early tumour stage (pT1) is
      questionable. Therefore, a limited resection of distal oesophagus and proximal
      stomach with two-field lymphadenectomy and jejunal interposition is an attractive
      alternative in early Barrett's carcinoma providing a low morbidity and mortality
      and resulting in a 90% chance of cure in patients without lymph node metastasis.

PMID- 12071090
TI  - [Barrett esophagus--esophageal carcinoma: conservative therapy and observation].
AB  - Chronic acid reflux is strongly associated with cancer of the esophagogastric
      junction and the main reason for the development of specialised intestinalised
      metaplasia in the esophagus (Barrett's esophagus). Endoscopic surveillance,
      therefore, is mandatory for long-segment Barrett's esophagus as well as short
      segment Barrett's. Videoendoscopy with four quadrant random biopsies are standard
      and new diagnostic tools like chromoendoscopy with methylene blue, magnifying
      endoscopy or fluorescence detection may turn out to be helpful. Differential
      surveillance strategies according to the recommendations of the American College
      of Gastroenterology and the Deutschen Gesellschaft fur Verdauungs- und
      Stoffwechselerkrankungen should be performed for medical and cost-efficiency
      reasons. Local endoscopic therapy of early cancer and high-grade dysplasia in
      Barrett's esophagus comprises three different methods: endoscopic mucosal
      resection (EMR), semiselective, athermal photodynamic therapy (PDT) and thermal
      techniques such as KTP- or Nd:YAG-laser and argon-plasma coagulation. All
      endoscopic methods have low morbidity and mortality rates compared to esophageal
      resection and therefore are an attractive alternative treatment option.
      Endoscopic mucosal resection is the treatment of choice for all localizable and
      circumscribed lesions, because the resected specimen can be classified with
      regard to the histopathological grading, complete resection and submucosal
      involvement, especially in view of patients who are surgical candidates. PDT is
      the best local treatment option for multifocal, not localizable or large
      superficial lesions, as large areas can be treated in a single therapeutic
      session. Thermal procedure are mainly auxiliary methods for the optimization of
      EMR or PDT. The shortterm and intermediate results of our studies appear to be
      promising in view of the high complete local remission rates in combination with
      the low morbidity and mortality.

PMID- 12071092
TI  - [Percutaneous endoscopic gastrostomy (PEG)].
AB  - Percutaneous endoscopic gastrostomy (PEG), although a standard method for long
      time enteral nutrition, still leaves uncertainty about details in indication,
      technique and complications. Based on own experiences (approximately 1000 PEG's
      and 170 EPJ's in the last 10 years) these topics are discussed. As new
      indications the PEG for decompression in chronic intestinal obstruction and the
      questionable relative contraindications ascites, peritoneal carcinosis and Morbus
      Crohn are discussed. The common thread-pull through-technique is recommended in a
      slightly modified variation, according to direct puncture techniques of small
      intestine: the cannulas inserted in the intestine are fixed by an endoscopic
      alligator forceps, thus facilitating precise puncture and raising safety for the
      patient due to avoidance of dislocation. As complications local infections,
      implantation metastases and the buried bumper syndrome have to be mentioned and
      avoided. Alternative methods for PEG and different exchange systems for more
      comfort for the patients are discussed finally.

PMID- 12071093
TI  - [Yearly changes in antibacterial activities of cefozopran against various
      clinical isolates between 1996 and 2000--I. Gram-positive bacteria].
AB  - The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems,
      against various clinical isolates obtained between 1996 and 2000 were yearly
      evaluated and compared with those of other cephems, oxacephems, carbapenems, and
      penicillins. Fifteen species, 1,062 strains, of Gram-positive bacteria were
      isolated from the clinical materials annually collected from January to December,
      and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 127),
      methicillin-resistant Staphylococcus aureus (MRSA; n = 123), Staphylococcus
      epidermidis (n = 104), Staphylococcus haemolyticus (n = 58), Streptococcus
      pyogenes (n = 100), Streptococcus agalactiae (n = 50), Streptococcus pneumoniae
      (n = 125), Enterococcus faecalis (n = 150), Enterococcus faecium (n = 50),
      Enterococcus avium (n = 50), and Peptostreptococcus spp. (P. anaerobius, P.
      asaccharolyticus, P. magnus, P. micros, P. prevotii; n = 125). CZOP possessed
      stable antibacterial activities against all strains tested throughout 5 years.
      The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while
      against S. pneumoniae and Peptostreptococcus spp., tended to increase year by
      year. However, the MIC90 just changed a little and were consistent with the
      results from the studies performed until the new drug application approval.
      Increases in the MIC90 against S. pneumoniae were also observed with cefpirome
      (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and
      imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also
      observed with ceftazidime (CAZ), CPR, CFPM, FMOX, SBT/CPZ, and IPM. The decreases
      in the sensitivities were not always considered to depend upon generation of
      resistant bacteria because the annual MIC range of each antibacterial agent was
      almost generally wide every year and the annual sensitivity of each strain to the
      agents extremely varied. In conclusion, the annual antibacterial activities of
      CZOP against the Gram-positive bacteria did not considerably change. It,
      therefore, was suggested that CZOP had maintained high antibacterial activity
      during 5 years of post-marketing.

PMID- 12071094
TI  - [Yearly changes in antibacterial activities of cefozopran against various
      clinical isolates between 1996 and 2000--II. Gram-negative bacteria].
AB  - The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems,
      against various clinical isolates obtained between 1996 and 2000 were yearly
      evaluated and compared with those of other cephems, oxacephems, and carbapenems.
      Thirty-two species 2,697 strains of Gram-negative bacteria were isolated from the
      clinical materials annually collected from January to December, and consisted of
      Moraxella subgenus Branhamella catarrhalis (n = 125), Escherichia coli (n = 250),
      Citrobacter freundii (n = 153), Citrobacter koseri (n = 97), Klebsiella
      pneumoniae (n = 150), Klebsiella oxytoca (n = 100), Enterobacter aerogenes (n =
      50), Enterobacter cloacae (n = 125), Serratia marcescens (n = 153), Proteus
      mirabillis (n = 103), Proteus vulgaris (n = 77), Morganella morganii (n = 141),
      Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii; n = 154),
      Pseudomonas aeruginosa (n = 211), Pseudomonas putida (n = 49), Burkholderia
      cepacia (n = 102), Stenotrophomonas maltophilia (n = 101), Haemophilus influenzae
      (n = 210), Acinetobactor baumannii (n = 63), Acinetobactor Iwoffii (n = 30),
      Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus,
      B. thetaiotaomicron; n = 129), and Prevotella spp. (P. melaninogenica, P.
      intermedia, P. bivia, P. oralis, P. denticola; n = 124). CZOP possessed stable
      antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C.
      koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P.
      mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A.
      lowffii throughout 5 years. The MIC90 of CZOP against those strains were
      consistent with those obtained from the studies performed until the new drug
      application approval. On the other hand, the MIC90 of CZOP against H. influenzae
      yearly obviously increased with approximately 65-time difference during study
      period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also
      yearly tended to rise. The present results demonstrated that CZOP had maintained
      the antibacterial activity against almost Gram-negative strains tested. However,
      the decrease in the antibacterial activity of CZOP against H. influenzae was
      suggested.

PMID- 12071095
TI  - [Antimicrobial activity of carbapenems and the combined effect with
      aminoglycoside against recent clinical isolates of Pseudomonas aeruginosa].
AB  - The carbapenem susceptibility of 32 strains of Pseudomonas aeruginosa recently
      isolated in Kakogawa municipal hospital was investigated. The MIC ranges of
      imipenem, panipenem, and meropenem were 0.25-16 mg/L, 0.5-16 mg/L, and < 0.03-4
      mg/L, respectively, and meropenem showed the highest antipseudomonal activity
      among the three carbapenems tested. In the analysis based on the MIC interpretive
      standards established by NCCLS, the resistance rates of test strains for
      imipenem, panipenem, and meropenem were 6.3%, 15.6%, and 0%, respectively. We
      also investigated the in vitro combined effect of imipenem or meropenem with
      amikacin against another 20 isolates of P. aeruginosa by checkerboard titration
      assay. Antagonism (minimum FIC index > 2) was not observed in any combinations
      against all strains tested. Super-additive effects (minimum FIC index < 1) in the
      combination of imipenem and amikacin were observed in eight (40%) strains tested.
      In contrast, in the combination of meropenem and amikacin, super-additive effects
      were observed in 14 isolates (70%). These results suggested that meropenem is
      superior to imipenem in combined effect with amikacin against P. aeruginosa. In
      conclusion, meropenem showed higher antipseudomonal activities than other
      carbapenems tested in both conditions, alone and in combination with amikacin.
      With regard to the clinical efficacy and prevention of antibiotic resistance,
      meropenem monotherapy or combination therapy with aminoglycoside is the most
      superior treatment for pseudomonal infections, and the findings in this study
      suggest that meropenem is still clinically very useful.

PMID- 12071096
TI  - [Rapid bactericidal activities of carbapenems against Pseudomonas aeruginosa in
      simulating human plasma concentrations].
AB  - The rapid bactericidal activities of panipenem (PAPM), imipenem (IPM), and
      meropenem (MEPM) against Pseudomonas aeruginosa were investigated by using in
      vitro pharmacodynamic model simulating the human plasma concentrations after
      intravenous drip infusion at 500 mg for 0.5 hours. Against P. aeruginosa PAO1,
      PAPM and IPM showed rapider reduction in viable cell counts than MEPM at 0.5
      hours after exposure. All drugs showed more than 3 log10 reduction in viable cell
      counts at 2 hours after exposure and bacterial regrowth was not observed
      throughout 6 hours. The initial bactericidal activities of the drugs against 4
      clinical isolates within 1 hour after exposure were also investigated by the same
      method. Against P. aeruginosa strain 12,475, the 3 drugs showed similar initial
      bactericidal activity but PAPM and IPM showed stronger initial bactericidal
      activity than MEPM against the other strains as did against P. aeruginosa PAO1.
      The morphological change of a strain 12,489, for which the initial bactericidal
      activities were different largely, after 0.5 hours exposure to simulated drug
      concentrations was investigated by scanning electron microscope. PAPM and IPM
      induced morphological changes in most of the cells and cell lysis and bulge
      formation. On the other hand, MEPM induced changes of the surface structure of
      cells and slightly elongated cells, but not cell lysis.

PMID- 12071097
TI  - [Changes of antibody titers during antimicrobial therapy including levofloxacin
      for Chlamydia infections in the obstetrics and gynecology field].
AB  - During the 6 years from May 1995, Chlamydia antibody titers were measured in
      nonpregnant and pregnant women. In positive patients, changes of the antibody
      titer during treatment as well as the transplacental passage of antibodies into
      cord blood were investigated. 1) Chlamydia antibody-positive patients (n = 45)
      received the following therapy and changes of the IgA and IgG antibody titers
      during treatment were investigated: Levofloxacin alone at 300 mg/day for 14 days
      (n = 29), additional clarithromycin at 400 mg/day for 14 days (n = 10),
      additional azithromycin at 500 mg/day for 3 days (n = 3), clarithromycin alone at
      400 mg/day for 14 days (n = 3). These patients were classified into four groups
      depending on either they were positive for both IgA and IgG (groups A-C) or were
      only positive for IgA or IgG (group D). Clearance of antibodies over time tended
      to be faster for IgA than IgG, but 25/38 (65.8%) showed negative for both
      antibodies after 6 years. 2) Antibody-positive women who were about 16 weeks
      pregnant (n = 61) were treated with clarithromycin (400 mg/day for 14 days) and
      the cord blood antibody titer was measured at the term of delivery. Cord blood
      IgA was not detected and IgG was strongly correlated with the maternal blood
      level (r = 0.945).

PMID- 12071098
TI  - Preventive effect of TAK-751S on complications of hemorrhagic colitis (results of
      clinical study of TAK-751S).
AB  - BACKGROUND: The effective therapy for hemolytic uremic syndrome and
      encephalopathy caused by enterohemorrhagic Escherichia coli have not been
      established. Great attention has been drawn to the results of the clinical study
      of TAK-751S, performed in Canada. In Japan, a nationwide clinical study of TAK
      751S had been performed since 1997 to investigate the preventive effect on the
      onset of HUS and the safety. METHODS: TAK-751S was administered in daily doses of
      500 mg/kg for one week to 128 pediatric patients with colitis who were suspected
      of enterohemorrhagic Escherichia coli (EHEC) infection. RESULTS: 1. TAK-751S was
      confirmed to absorb Shiga toxin (Stx) existing inside the human intestine and to
      excrete Stx out of the body. 2. The incidence of HUS is 5.9% (4/68) and a
      tendency to inhibit the onset of HUS was observed as compared with the historical
      control. The complications of central neuropathy such as encephalopathy were
      observed in 3 of these patients with HUS. 3. Mild "sweating" and "nausea" were
      observed. There were 13 mild non-specific abnormalities of laboratory test values
      in 8 patients. CONCLUSIONS: From these results, it was clarified that TAK-751S
      absorbed and removed free Stx in the intestinal tract of pediatric patients with
      EHEC infection. The test drug could not inhibit the onset of HUS completely, but
      since HUS occurred within 48 hours after the start of administration in 3 of the
      4 patients with onset of HUS, TAK-751S is a safe drug for pediatric patients with
      EHEC infection in which the preventive effect on HUS and encephalopathy are
      expected when it can be given from an early stage of the diseases. Furthermore,
      these results suggest that importance of rapid diagnosis of HUS.

PMID- 12071099
TI  - Psychiatrists' perception of psychiatric commitment.

PMID- 12071100
TI  - Impact of overcrowding and legislational change on the incidence of suicide in
      custody experiences in Austria, 1967-1996.

PMID- 12071101
TI  - Psychiatric symptoms, history of victimization, and violent behavior among
      incarcerated female felons: an American perspective.

PMID- 12071102
TI  - The critical perspective in psychological jurisprudence theoretical advances and
      epistemological assumptions.
AB  - The critical perspectives of psychological jurisprudence identified above, along
      with their corresponding epistemological assumptions, reflect a radical agenda
      for change at the law-psychology divide. Although not exhaustively reviewed, the
      individual theories represent different approaches by which structural reform can
      be enacted and citizen well-being can therefore be realized. Collectively, the
      critical perspectives and their attending presuppositions challenge conventional
      wisdom about prospects for transforming (i.e., humanizing) the legal apparatus. I
      submit that the future viability of the law-psychology movement, and its overall
      utility for society, considerably depends on its capacity to facilitate and
      secure such widespread change. By focusing on critical theoretical inquiry, this
      article makes painfully clear that much of what is wrong with the legal system,
      especially in its interactions with and interpretations of people, cannot be
      amended or solved through it. Indeed, as Roesch (1995) observed, "changes in the
      justice system will never be sufficient to create a just society, nor will within
      system changes by themselves ever have much of an impact on individuals who come
      into conflict with the law" (p. 3). I agree. Accordingly, it is time to move on
      and, where necessary, to look elsewhere for guidance. The radical agenda in
      psychological jurisprudence represents a provocative strategy, providing a
      meaningful basis for critique and a sustainable basis for reform. Both are
      integral to the call for justice embodied in the founding of the AP-LS decades
      ago. Realizing this challenge, however, remains an unfulfilled dream. Thus, the
      task that awaits is to apply the insights of critical psychological jurisprudence
      to relevant areas of research and policy. I submit that the academy can ill
      afford to dismiss this task. Indeed, in the final analysis, to do so would not
      only defer prospects for justice but would destroy its very possibility,
      especially for citizens disillusioned by the status quo and desperate for change
      that makes a difference.

PMID- 12071103
TI  - Primary erotic preference in a group of child molesters.

PMID- 12071104
TI  - Weapon focus in sexual assault memories of prostitutes.

PMID- 12071105
TI  - Paternalism and autonomy: a presentation of a Nordic study on the use of coercion
      in the mental health care system.

PMID- 12071106
TI  - Schwannoma of the seminal vesicle.
AB  - A 79-year-old man presented with a history of nocturia. On rectal examination a
      solid mass above the prostate gland was discovered. Computerized tomography (CT)
      and ultrasound (US) showed that the mass was solid and was arising from the
      seminal vesicle. After a needle biopsy, pathology and immunocytochemistry
      confirmed the mass to be Schwannoma. Tumors of the seminal vesicle are rare. To
      our knowledge Schwannoma of the seminal vesicle has not been described before.

PMID- 12071107
TI  - Fatal case of inhalational anthrax mimicking intra-abdominal sepsis.
AB  - In this report, we discuss the second fatal case of inhalational anthrax related
      to the use of Bacillus anthracis spores as a biological weapon in the United
      States. This case highlights two of the major characteristics of inhalational
      anthrax: the fulminating nature of the infection and the difficulty of promptly
      establishing a diagnosis. In the patient discussed here, gastrointestinal
      symptoms and findings were so impressive that the patient was thought to have a
      primary intra-abdominal condition. In the current situation, in which
      bioterrorism is a real threat, any patient presenting with a flulike or
      gastrointestinal illness should be queried about their occupation. Anyone with
      evidence of systemic disease who resides or works in a geographical region where
      anthrax cases are occurring should be treated until the diagnosis of anthrax is
      excluded. In the United States, the group that is at high risk for anthrax has
      shifted from rural farm workers to city dwellers, especially postal workers and
      public figures.

PMID- 12071108
TI  - Nateglinide, a new agent for postprandial glucose control in type 2 diabetes.

PMID- 12071109
TI  - Problem and pathological gambling.

PMID- 12071110
TI  - Professionalism and trust.

PMID- 12071111
TI  - Primary-care physicians' premiums.

PMID- 12071112
TI  - Milk fever control principles: a review.
AB  - Three main preventive principles against milk fever were evaluated in this
      literature review, and the efficacy of each principle was estimated from the
      results of controlled investigations. Oral calcium drenching around calving
      apparently has a mean efficacy of 50%-60% in terms of milk fever prevention as
      well as prevention of milk fever relapse after intravenous treatment with calcium
      solutions. However, some drenches have been shown to cause lesions in the
      forestomacs. When using the DCAD (dietary cation-anion difference) principle,
      feeding rations with a negative DCAD (measured as (Na + K)-(Cl + S))
      significantly reduce the milk fever incidence. Calculating the relative risk (RR)
      of developing milk fever from controlled experiments results in a mean RR between
      0.19 and 0.35 when rations with a negative versus positive DCAD are compared. The
      main drawback from the DCAD principle is a palatability problem. The principle of
      feeding rations low in calcium is highly efficient in milk fever prevention
      provided the calcium intake in the dry period is kept below 20 g per day.
      Calculating the relative risk (RR) of developing milk fever from controlled
      experiments results in a very low mean RR (between 0 and 0.20) (daily calcium
      intake below versus above 20 g/d). The main problem in implementing the low-Ca
      principle is difficulties in formulating rations sufficiently low in calcium when
      using commonly available feeds. The use of large doses of vitamin D metabolites
      and analogues for milk fever prevention is controversial. Due to toxicity
      problems and an almost total lack of recent studies on the subject this principle
      is not described in detail. A few management related issues were discussed
      briefly, and the following conclusions were made: It is important to supply the
      periparturient cow with sufficient magnesium to fulfil its needs, and to prevent
      the dry cows from being too fat. Available information on the influence of
      carbohydrate intake, and on the effect of the length of the dry period and
      prepartum milking, is at present insufficient to include these factors in control
      programmes.

PMID- 12071113
TI  - Comparisons of sampling procedures and time of sampling for the detection of
      Salmonella in Danish infected chicken flocks raised in floor systems.
AB  - Bacteriological follow-up samples were taken from 41 chicken (Gallus gallus)
      flocks in floor systems, where Salmonella enterica (Salmonella) had been detected
      either directly in bacteriological samples or indirectly by serological samples.
      Three types of follow-up samples were compared to each other within each flock:
      1) 5 pairs of socks, analysed as 5 samples, 2) 2 pairs of socks, analysed as one
      sample, and 3) 60 faecal samples, analysed as one pooled sample. Agreement
      between sampling methods was evaluated by the following statistical tests:
      'Kappa', 'The adjusted rand', McNemar's test for marginal symmetry, Proportion of
      agreement P0, P+, P-, and Odds Ratio. The highest agreement was found between the
      2 types of sock sampling, while the lowest agreement was found by comparing 60
      faecal samples with 5 pairs of socks. Two pairs of socks analysed as one pool
      appeared to be just as effective in detecting S. enterica as the 60 faecal
      samples. In broiler flocks, 5 pairs of socks were used both in the routine
      samples taken at about 3 weeks of age for the establishment of infection of the
      flock, and as one of the follow-up samples taken shortly before slaughter age,
      which means that the only notable differences between the 2 sampling rounds were
      the age of the broilers and of their litter. S. enterica was detected more
      frequently in samples from broilers about 3 weeks old, than in similar samples
      taken from broilers a few days prior to slaughter at ca. 33-40 days of age.

PMID- 12071114
TI  - Antimicrobial susceptibility of udder pathogens isolated from dairy herds in the
      west littoral region of Uruguay.
AB  - A total of 522 strains belonging to streptococci, enterococci and staphylococci
      isolated from sub-clinical and clinical cases of bovine mastitis from the west
      littoral region of Uruguay were analysed for their susceptibility to several
      antimicrobial agents. The susceptibility patterns were studied by agar disk
      diffusion methods (ADDM) and broth micro-dilution to determine the minimum
      inhibitory concentration (MIC). The concentration that inhibits 90% (MIC90) of
      the analysed strains reported in micrograms per millilitre, for Staphylococcus
      aureus were > 8, 8, < or = 0.5, < or = 4, < or = 1, < or = 0.5, > 64, < or =
      0.25, 0.5, < or = 1 and < or = 1 to penicillin, ampicillin, oxacillin,
      cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin,
      trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase
      negative staphylococci (CNS) had different values for penicillin (4) and
      ampicillin (2), while the other antimicrobial agents had the same MIC90 values as
      reported for S. aureus. The MIC90 values for streptococci were 0.12, 0.25, < or =
      4, 16, < or = 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin,
      erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC90
      for enterococci were 4, 4, 4, < or = 0.5, 2, > 8 for penicillin, ampicillin,
      gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole,
      respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to
      penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the
      streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43
      enteroccocal strains were resistant. Non significant statistical differences were
      found between the results obtained by ADDM and broth micro-dilution for
      classifying bacterial isolates as susceptible or resistant according to the
      National Committee of Clinical Laboratory Standards.

PMID- 12071115
TI  - Salmonella in sheep in Iceland.
AB  - In 1995 several outbreaks of food poisoning in humans occurred in Iceland, that
      were traced to salmonella contamination of singed sheep heads. This prompted us
      to study the prevalence of salmonella infection in sheep and to trace where and
      how infection might have occurred. Faecal, intestinal contents and tonsillar
      samples were collected in the spring and autumn from sheep on 50 farms in the
      southwestern part of the country, where salmonellosis had been detected and from
      5 farms in the northwestern part of the country. All faecal samples from the
      southwest were negative, whereas samples from 3 farms obtained in the autumn in
      the northwest were positive. Tonsillae taken in the autumn were positive in sheep
      from 3 farms in the southwest and 2 in the northwest. Our results show that
      salmonella infection is rare in Icelandic sheep but healthy carriers my harbour
      the bacteria in tonsillae. Salmonella was not detected in drainage from
      slaughterhouses nor in singed sheep heads.

PMID- 12071117
TI  - Case report on abnormal progesterone pattern in a mare showing oestrus during the
      breeding season.

PMID- 12071116
TI  - Influence of boar and semen parameters on motility and acrosome integrity in
      liquid boar semen stored for five days.
AB  - Ninety ejaculates from a total of 76 AI boars were extended in Beltsville Thawing
      Solution (BTS). Boar identity, breed, weight of the ejaculate and sperm
      concentration were registered. Motility and acrosome integrity were assessed
      after storage at 16-18 degrees C for 6, 30, 54, 78, and 102 h. Storage time had a
      significant influence on both motility (p < 0.01) and acrosome integrity (p <
      0.001). The Least Square Means for percentage of motility showed a small decline
      from 79.8% after 6 h of storage to 78.4% at 102 h. Motility at 78 and 102 h was
      significantly different from motility at 6 h (p < 0.05). The percentage of sperm
      cells with normal acrosomes declined throughout the experiment. The Least Square
      Means for 6, 30, 54, 78, and 102 h of storage were 93.9%, 90.6%, 88.0%, 84.8%,
      and 78.2%, respectively. The decrease in acrosome integrity from one storage time
      to the next was highly significant throughout the trial (p < 0.001). There was a
      significant influence of boar (p < 0.001) and sperm concentration (p < 0.01) on
      motility, while acrosome integrity was affected only by boar (p < 0.001). Breed
      of the boars and weight of the ejaculate did not influence the dependent
      variables.

PMID- 12071118
TI  - The National Nursing Home Survey: 1999 summary.
AB  - OBJECTIVE: This report presents estimates of nursing homes and their current
      residents and discharges in the United States. The data are summarized by
      characteristics of facilities such as information about Medicare and Medicaid
      certification, bed size, type of ownership, services provided, and per diem
      rates. Data are also summarized by characteristics of current residents and
      discharges such as demographic and resident characteristics, health and
      functional status, services provided, primary diagnosis, and all-listed
      diagnoses. METHODS: Estimates in this report are from the 1999 National Nursing
      Home Survey (NNHS), the sixth in a series of surveys. This nationwide sample
      survey was conducted by the National Center for Health Statistics, Centers for
      Disease Control and Prevention, from July through December 1999. RESULTS: About
      1.6 million current residents and 2.5 million discharges received nursing home
      care during 1999. About two-thirds (67 percent) of nursing homes are proprietary
      (for profit) and are located in the Midwest and South. There were 1.5 million
      full-time equivalent (FTE) employees providing health-related services to
      residents. Ninety percent of current residents were age 65 years or over, 72
      percent were female, and 57 percent were widowed. Nearly half (46 percent) of
      current residents were admitted from a hospital. The average length of time since
      admission for current residents was 892 days. Most nursing home discharges were
      female (62 percent) and 88 percent were age 65 years and over. The main reasons
      for most discharges were admission to a hospital (29 percent) and death (24
      percent). The average length of stay for a discharge was 272 days.

PMID- 12071119
TI  - [NSAIDs and the PPAR-gamma receptor].

PMID- 12071120
TI  - [Gene therapy--the method of the future for causal treatment of diabetes?].

PMID- 12071121
TI  - [Chance and calculated development! The history of oral antidiabetics].

PMID- 12071122
TI  - [The chemotherapeutic use of antidiabetics. Sulfonylurea compounds and glinides].

PMID- 12071123
TI  - [Therapeutic renaissance. Biguanides in type-2 diabetes: metformin].

PMID- 12071124
TI  - [Reducing postprandial glucose levels. Glucosidase antagonists].

PMID- 12071125
TI  - [Against insulin resistance. Insulin sensitizers].

PMID- 12071126
TI  - [A therapeutic option for type-2 diabetes. The incretion hormone GLP-1].

PMID- 12071127
TI  - [Weight reduction. Antiobesity drug treatment in type-2 diabetics].

PMID- 12071129
TI  - [New guidelines for nutrition in diabetics. Diet in change].

PMID- 12071128
TI  - [What are the costs of type-2 diabetes? Pharmacoeconomics].

PMID- 12071130
TI  - [Quality control in drugs--an international function].

PMID- 12071131
TI  - [DPhG--Foundation for Promotion of Young Scientific Talent. The awarding of
      stipends for promotion of young scientists in the field of pharmacy].

PMID- 12071132
TI  - [From intensive care to palliative care].

PMID- 12071133
TI  - [Giving birth at death: dying at a palliative care home. Witness account].

PMID- 12071134
TI  - [Spiritual management of patients: neutrality does not exist].

PMID- 12071135
TI  - [Evaluation of the impact of clinical training on palliative care].

PMID- 12071136
TI  - [Medication at the end of life, practice in Rive Neuve between knowledge and
      ignorance].

PMID- 12071137
TI  - [Depression in palliative care: how to identify it, detect it, and treat it].
AB  - Psychological symptoms are frequently observed in palliative care, such as
      anxiety, mood disorders, depression and death request. However, these symptoms
      are considered most of the time as a natural and emotional process of any
      terminally ill patient. This may result in under-diagnosis and under-treatment.
      Recognition early detection of depressive symptoms is necessary to achieve an
      efficient management. Better information and key skill training should thus be
      implemented together with screening in order to help depressive patients and
      their relatives during dying and mourning processes.

PMID- 12071138
TI  - [Alcohol and psychiatric crisis: motivation during the crisis].

PMID- 12071139
TI  - [Audiometric test in middle-school].

PMID- 12071140
TI  - [In vitro hepatitis C. Elimination of lipoproteins associated with cells: an
      important stage to obtain an efficient infection of human hepatocytes by the
      hepatitis C virus].

PMID- 12071141
TI  - [Company at the end of life: position of the Suisse Alzheimer Association
      (summary)].

PMID- 12071142
TI  - [Position of the cantonal Commission of ethics regarding assisted suicide in the
      EMS].

PMID- 12071143
TI  - [Magnet-retained orbital-zygomatic prosthesis--a case report].

PMID- 12071144
TI  - [Evaluation of oral therapy methods in the treatment of snoring and obstructive
      sleep apnea].

PMID- 12071145
TI  - In Memoriam. Inge Edler: the father of echocardiography.

PMID- 12071146
TI  - Inge Edler and the origins of clinical echocardiography.

PMID- 12071147
TI  - The sky's the limit.

PMID- 12071148
TI  - Giver us a clue on PREP.

PMID- 12071149
TI  - Think it over.

PMID- 12071150
TI  - Putting the money where the mouse is.

PMID- 12071151
TI  - Freedom with the net.

PMID- 12071152
TI  - [Abstracts of the XXVI Francophone Meeting of Digestive Pathology. Nantes,
      France, 23-27 March 2002].

PMID- 12071153
TI  - Peri-partum changes in the intraepithelial lymphocyte population of sheep
      interplacentomal endometrium.
AB  - PROBLEM: Previous studies have shown that the proportion of gammadeltaTCR+ large
      granulated lymphocytes (LGLs) increased markedly during pregnancy and declined
      dramatically by 2 days after parturition in sheep interplacentomal uterine
      epithelium. In the present study, the distribution, dynamics and fate of these
      cells, just before, during and immediately after parturition are described.
      METHODS OF STUDY: Interplacentomal tissues were collected at 140 days postcoitus
      (dpc), 148 dpc, during parturition, 1-2 hr postpartum, 1 day postpartum (dpp) and
      3 dpp, and were studied using light and electron microscopy, and immuno
      histochemistry. Uterine washings were collected at 148 dpc and examined for the
      presence of LGLs. Semi-thin Araldite sections taken at different stages were used
      to quantify the intraepithelial LGLs, non-granulated lymphocytes (NGLs) and
      apoptotic cells, whereas frozen sections were used to quantify CD45R+, CD8+ and
      gammadeltaTCR+ intraepithelial lymphocytes (IELs). RESULTS: A dramatic decline in
      the proportion of IELs in the luminal epithelium during parturition was observed,
      mainly because of the decline in CD45R+, CD8+ and gammadeltaTCR+ IELs. There was
      also a significant decline in the number of granules/ LGL at parturition. This
      was accompanied by the presence of apoptotic cells of which some were LGLs. The
      proportions of IELs, LGLs and apoptotic cells markedly increased at 3 dpp. LGLs
      were found both in uterine washings at 148 dpc and in the uterine lumen at 3 dpp.
      Apoptosis of glandular epithelial cells was also evident at parturition and
      markedly increased at 1 dpp. CONCLUSIONS: Our results demonstrated that the
      dramatic decline in the proportion of gammadeltaTCR+ LGLs at parturition was
      because of de-granulation, apoptosis and migration of these cells into the
      uterine lumen.

PMID- 12071154
TI  - Vitamin D receptor genotypes are not associated with clinical response to
      calcipotriol in Korean psoriasis patients.
AB  - Conflicting results have been reported on the association between BsmI
      restriction fragment length polymorphism (RFLP) at the vitamin D receptor gene
      (VDR) locus and the clinical response of psoriasis patients to calcitriol or
      calcipotriol therapy. We evaluated RFLPs of the VDR gene by analyzing the
      restriction pattern of polymerase chain reaction products in 55 Korean psoriasis
      patients receiving topical calcipotriol therapy, and evaluated the clinical
      response. Of the 55 patients, 43 completed the 8-week treatment protocol, and the
      response was evaluated as excellent in 9 patients, good in 20, and poor in 14.
      Thus, in our 43 patients BsmI and ApaI polymorphism in the VDR gene did not
      correlate with response to calcipotriol. The marked predominance of the b allele
      in the Korean population precludes the possibility that BsmI polymorphism is
      associated with clinical response to calcipotriol. The pattern of prevalence of
      the VDR genotypes in the Korean population is very different from that in Western
      populations. There were no differences in VDR genotype between controls and
      psoriasis patients at the BsmI site, but there were significant difference in
      terms of ApaI RFLP as previously reported. In conclusion, polymorphism analysis
      of the VDR gene with BsmI and ApaI restriction enzymes in psoriasis patients was
      not helpful in predicting clinical response to calcipotriol.

PMID- 12071155
TI  - Tight junction proteins: a novel class of integral membrane proteins. Expression
      in human epidermis and in HaCaT keratinocytes.
AB  - Tight junction proteins comprise a novel group of integral membrane proteins
      necessary for cell-to-cell contacts and responsible for the barrier function in
      epithelial and endothelial cells in various tissues. The tight junction membrane
      domain contains at least three distinct proteins, named occludin, claudin and
      junctional adhesion molecule. Claudins are products of a gene family consisting
      of more than 20 members. We investigated mRNA expression of occludin and 13
      different claudins in neonatal foreskin, adult skin and cultivated HaCaT
      keratinocytes by the Northern blot technique, and performed immunohistochemical
      staining of adult skin for occludin, claudin 1 and claudin 2. Occludin, claudin 1
      and claudin 3 mRNAs were expressed in human neonatal and adult keratinocytes as
      well as in HaCaT keratinocytes. All other tested claudins were negative.
      Immunohistochemical staining of adult skin was positive for occludin in the
      intercellular space of the granular layer, and for claudin 1 in the inter
      cellular space of the spinosum layer and basal layer, but negative for claudin 2
      in all skin layers. Claudin 1 was also positive in the outer root sheath of hair
      follicles. Our results indicate that occludin, claudin 1 and claudin 3 are
      involved in cell-to-cell contacts between keratinocytes in human epidermis,
      although their functional importance remains unknown.

PMID- 12071157
TI  - Guidelines on how to assess the validity of results presented in subgroup
      analysis of clinical trials.
AB  - In observational studies, identification of associations within particular
      subgroups is the usual method of investigation. As an exploratory method, it is
      the bread and butter of epidemiological research. Nearly everything that has been
      learned in epidemiology has been derived from the analysis of subgroups. In a
      randomized clinical trial, the entire purpose is the comparison of the test
      subjects and the controls, and when there is particular interest in the results
      of treatment in a certain section of trial participants, a subgroup analysis is
      performed. These subgroups are examined to see if they are liable to a greater
      benefit or risk from treatment. Thus, analyzing patient subsets is a natural part
      of the process of improving therapeutic knowledge through clinical trials.
      Nevertheless, the reliability of subgroup analysis can often be poor because of
      problems of multiplicity and limitations in the numbers of patients studied. The
      naive interpretation of the results of such examinations is a cause of great
      confusion in the therapeutic literature. We emphasize the need for readers to be
      aware that inferences based on comparisons between subgroups in randomized
      clinical trials should be approached more cautiously than those based on the main
      comparison. That is, subgroup analysis results derived from a sound clinical
      trial are not necessarily valid; one must not jump to conclusions and accept the
      validity of subgroup analysis results without an appropriate judgment.

PMID- 12071158
TI  - Monitored transtracheal jet ventilation using a triple lumen central venous
      catheter.
AB  - Two patients with nasopharyngeal carcinoma, radiotherapy treatment and
      'difficult' airways were anaesthetised for oral surgery. A triple lumen central
      venous catheter was inserted through the cricoid membrane and transtracheal jet
      ventilation with an AMS 1000 jet ventilator was performed via the distal lumen.
      The middle and proximal lumens were connected to an airway pressure monitor and a
      capnograph, enabling breath-by-breath monitoring of ventilation.

PMID- 12071156
TI  - Characterization of the inflammatory infiltrate and expression of endothelial
      cell adhesion molecules in lupus erythematosus tumidus.
AB  - Lupus erythematosus tumidus (LET) is a disease with characteristic clinical and
      histopathologic features that has not always been considered a subset of
      cutaneous lupus erythematosus (CLE). Although LET was first mentioned in the
      literature in 1930, it has rarely been documented, and immunohistochemical
      studies have never been performed. The aim of the present study was to
      characterize the inflammatory infiltrate and to analyze the expression of
      endothelial cell adhesion molecules in skin specimens from patients with LET and
      to compare the results with those from patients with other variants of CLE, such
      as discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus
      (SCLE). Cryostat sections of lesional skin specimens from ten patients with LET
      demonstrated an infiltrate composed of more than 75% CD4+, CD8+, and HLA-DR+
      cells. Interestingly, CD45RO+ cells, in contrast to CD45RA+ cells, were the
      prevailing inflammatory cell population. Compared with skin specimens from
      patients with DLE and SCLE, the mean expression of CD4+ and CD8+ cells was higher
      (but not significantly so) in LET, and no differences were observed with the
      other three antibodies. Furthermore, in contrast to controls, intercellular
      adhesion molecule-1, vascular adhesion molecule-1, E-selectin, and P-selectin
      showed the same expression pattern in skin specimens from patients with DLE,
      SCLE, and LET. In conclusion, the inflammatory infiltrate of LET primarily
      consists of CD4+/CD8+ lymphocytes. Furthermore, expression of endothelial cell
      adhesion molecules was equally upregulated in LET compared with the expression in
      DLE and SCLE, suggesting a similar immunopathomechanism of these subtypes of CLE.

PMID- 12071159
TI  - An unusual case of stridor after thyroidectomy.
AB  - Twelve days after subtotal thyroidectomy, an air pocket developed in a patient's
      neck. The pressure in this pocket had gradually increased as small amounts of
      air, probably associated with coughing, came out of a tiny hole in the trachea to
      form a pneumocoele. This produced limited surgical emphysema, causing venous
      congestion and oedema of the soft tissues of the larynx, which in turn led to
      increasing airway obstruction. We believe that this is the first reported case of
      a pneumocoele that gradually increased in size, causing airway obstruction that
      was almost certainly due to secondary laryngeal oedema.

PMID- 12071160
TI  - A survey of physicians' attitudes to transfusion practice in critically ill
      patients in the UK.
AB  - This study aimed to examine the attitudes of intensivists and haematologists to
      the use of blood and blood products using a scenario-based postal questionnaire.
      One hundred and sixty-two intensivists and 77 haematologists responded to the
      survey. In four scenarios, the baseline haemoglobin thresholds for red cell
      transfusion ranged from 6 to 12 g.dl(-1). There was significant variation between
      scenarios (p <0.005). Increasing age, high Acute Physiology and Chronic Health
      Status II score, surgery, acute respiratory distress syndrome, septic shock and
      lactic acidosis significantly (p <0.005) modified the transfusion threshold.
      There were greater variations in the baseline threshold for platelet transfusion.
      The majority of respondents (72.3%) selected a baseline haemoglobin threshold
      between 9 and 10 g.dl(-1). The thresholds for platelet transfusion were far less
      consistent.

PMID- 12071161
TI  - Palliative care and pain management 1.

PMID- 12071162
TI  - Palliative care and pain management 2.

PMID- 12071163
TI  - Keep calf compression in the Lloyd-Davies position.

PMID- 12071164
TI  - Peri-operative fluid management in the elderly patient.

PMID- 12071165
TI  - House officers and the sick ward patient.

PMID- 12071166
TI  - New Deal and manpower requirements--a simplified formula.

PMID- 12071167
TI  - Useless ritual?

PMID- 12071168
TI  - Predicting difficult intubation 1.

PMID- 12071169
TI  - The value of airway assessment.

PMID- 12071170
TI  - Oral aphthous ulcers after difficult intubation in a patient with Behcet's
      disease.

PMID- 12071171
TI  - Sevoflurane vs. isoflurane: a clinical comparison in a day surgery.

PMID- 12071172
TI  - Anaesthesia and the oral contraceptive pill.

PMID- 12071173
TI  - Cannabis abuse and laryngospasm.

PMID- 12071174
TI  - An unusual case of thrombocytopaenia.

PMID- 12071175
TI  - Yes, for updating the guidelines for day case surgery; and please stick to it.

PMID- 12071176
TI  - Pulmonary oedema in fit patients of African origin 1.

PMID- 12071177
TI  - Swearing--another means of assessing ease of intubation!

PMID- 12071178
TI  - Pulmonary oedema in fit patients of African origin 2.

PMID- 12071180
TI  - The moral and ethical quandry of embryonic stem cell research.

PMID- 12071179
TI  - Tattoo medi-alert.

PMID- 12071181
TI  - Update from Seattle: the 9th Annual Retrovirus Conference.

PMID- 12071183
TI  - Perinatal HIV prevention aims for elimination.

PMID- 12071182
TI  - Policy watch. Good news, bad news.

PMID- 12071184
TI  - The switching spiral: a triumph of hope over benefit?

PMID- 12071185
TI  - Achieving adherence with antiretroviral medications for pediatric HIV disease.
AB  - Factors influencing antiretroviral adherence for 42 HIV-positive children were
      elicited from primary caregivers, and the perspectives of families and clinicians
      regarding success with adherence were compared. Interviews in preferred language
      (Spanish or English), chart reviews, and visual analogue scales (VAS) were used.
      Adherence was high by traditional markers of prescriptions filled (100%), doses
      reported taken (97%), and appointments kept (88%). Clinicians estimated slightly
      but not significantly lower adherence than did families using the VAS. Sixty-four
      percent of families reported barriers to adherence, and 30% reported strategies
      that differ from those in the general adherence literature. Adherence strategies
      devised by families depended heavily on family support and resolution of
      disclosure issues in the household.

PMID- 12071186
TI  - Editorial comment: challenges to pediatric adherence to antiretroviral
      medications.

PMID- 12071187
TI  - Condyloma acuminatum presenting as a dorsal tongue lesion in a patient with AIDS.
AB  - Oral lesions have been recognized as a prominent feature of HIV infection and
      AIDS since the beginning of the epidemic. This report describes the case of a man
      with advanced AIDS and a nonpainful but enlarging dorsal tongue soft tissue
      growth of 6 months' duration. Incisional biopsy showed a red, papillary lesion
      with koilocytosis consistent with condyloma acuminatum. In situ hybridization and
      molecular techniques were used to identify human papillomavirus (HPV)-31
      sequences in warty tissue. Eighteen months later, the lesion recurred and was
      reexcised without complication. This case is reported to illustrate that venereal
      transmission may not be as important in warts of the oral cavity as in HIV
      associated anogenital warts, because warts of the oral cavity are rarely
      associated with HPV types 6, 11, 16, and 18. Instead, they may be present as a
      result of activation of latent HPV infection or perhaps autoinfection from skin
      and facial lesions. The carcinogenic potential of oral warts in HIV disease is
      undefined, as is the role of antiretroviral therapy in controlling HPV-associated
      oral lesions.

PMID- 12071188
TI  - Nevirapine-associated toxicity.

PMID- 12071190
TI  - Pat West: thinking ahead of the curve.

PMID- 12071189
TI  - Editorial comment: issues with HIV and oral human papillomavirus infections.

PMID- 12071191
TI  - An article of change.

PMID- 12071192
TI  - SANE (sexual assault nurse examiner) programs have benefits you can't ignore.

PMID- 12071193
TI  - [Report from the XVII general meeting of members from the Polish Biochemical
      Society].

PMID- 12071194
TI  - [Treatment outcome after surgical management of osseous breast carcinoma
      metastases. Preventive stabilization vs. management after pathological fracture].
AB  - AIM OF THE STUDY, METHOD: The advantages of a prophylactic care of fracture
      endangered, osseous metastasis of the mammary cancer stand opposite to the
      perioperative risk and to conservative alternatives. As a pathologic fracture
      cannot surely be excluded while performing a conservative proceeding, a
      retrospective trial was set up to compare the results of treatment after a
      pathologic fracture (n = 35) with those undergoing a prophylactic attendance (n =
      44). RESULTS: The intraoperative, cardio-pulmonary complications were distributed
      in balance totally amounting to 20.3% (n = 16). Intraoperative complications
      concerning surgical procedure (n = 3) exclusively occurred within the fracture
      group. Generally, postoperative complications arose in 20.3% (n = 16) of all
      cases, in which the patients belonging to the fracture group were increasingly
      afflicted [28.6% (n = 11/35) vs. 11.4% (n = 5/44); p < 0.02]. While there were no
      differences between both groups concerning the postoperative, surgery-technical
      complications, significantly more patients (91.8% [n = 40/44]) of the
      prophylactic-care group achieved a complete postoperative usability of the
      operated area than in the fracture-group [74.3% (n = 26/35)] (p < 0.05). The
      average survival time tended to be longer within the prophylactic-care group
      [19.3 +/- 15.6 month (prophylactic-care group) vs. 15.0 +/- 16.9 month (fracture
      group)]. CONCLUSIONS: The prophylactic treatment of fracture endangered, osseous
      metastasis of the mammary cancer leads to reduction of the general, postoperative
      complications compared to the patients with a pathologic fracture. Further, those
      patients have a better chance to recover full mobility after surgery. Considering
      the long survival time after the incidence of osseous metastasis at the mammary
      cancer a prophylactic treatment represents the method of first choice compared
      with the conservative treatment which persistently contains the risk of
      fracturing.

PMID- 12071196
TI  - Non-ionizing radiation, Part 1: static and extremely low-frequency (ELF) electric
      and magnetic fields.

PMID- 12071197
TI  - Abstracts of the 54th Annual Meeting of the American Association of Clinical
      Chemistry. Orlando, Florida, USA. July 28-August 1, 2002.

PMID- 12071198
TI  - Abstracts of the 3rd World Conference on Neurorehabilitation. April 2-6, 2002.
      Venice, Italy.

PMID- 12071199
TI  - Ethics in journalism.

PMID- 12071201
TI  - Abstracts of the 25th Annual Conference on Shock. Big Sky, Montana, USA. June 8
      11, 2002.

PMID- 12071200
TI  - Abstracts of the 16th Congress of the European Sleep Research Society. 3-7 June
      2002. Reykjavik, Iceland.

PMID- 12071202
TI  - Chemical castration of sex offenders: "a shot in the arm" towards rehabilitation.

PMID- 12071203
TI  - Understanding the issues of organ and tissue donation, allocation and payment.

PMID- 12071204
TI  - Confidentiality and right to privacy issues in mental health managed care.

PMID- 12071205
TI  - Facing the limits on uses of medical and peer review information: are high
      technology and confidentiality on a collision course?

PMID- 12071206
TI  - The role of nonlinear dynamics of the syrinx in the vocalizations of a songbird.
AB  - Birdsong is characterized by the modulation of sound properties over a wide image
      of timescales. Understanding the mechanisms by which the brain organizes this
      complex temporal behaviour is a central motivation in the study of the song
      control and learning system. Here we present evidence that, in addition to
      central neural control, a further level of temporal organization is provided by
      nonlinear oscillatory dynamics that are intrinsic to the avian vocal organ. A
      detailed temporal and spectral examination of song of the zebra finch
      (Taeniopygia guttata) reveals a class of rapid song modulations that are
      consistent with transitions in the dynamical state of the syrinx. Furthermore, in
      vitro experiments show that the syrinx can produce a sequence of oscillatory
      states that are both spectrally and temporally complex in response to the slow
      variation of respiratory or syringeal parameters. As a consequence, simple
      variations in a small number of neural signals can result in a complex acoustic
      sequence.

PMID- 12071207
TI  - The proposed model surrogate parenthood act: a legislative response to the
      challenges of reproductive technology.
AB  - In this Article, Manus proposes a Model Surrogate Parenthood Act. He examines the
      medical and scientific history of surrogacy and reviews the jurisprudence in the
      area, specifically the constitutional relationship between procreation rights and
      surrogacy. The author asserts that surrogate motherhood cannot be, and indeed,
      should not be, eradicated through legislation criminalizing it. The proposed
      Model Act, presented here in its entirety, attempts to reduce the problems
      inherent in the concept of surrogate parenthood by putting the process under
      strict court supervision and by zealously protecting the rights of the surrogate
      mother and the child to be conceived.

PMID- 12071208
TI  - Stumbling toward equity: the role of government in kidney transplantation.
AB  - In Mortal Peril, Professor Epstein is critical of the current, regulated system
      for organ donation and suggests that a market for organ tissue would better meet
      the needs of patients. In this response to Professor Epstein, Professor Laura
      Dooley and Dr. Robert Gaston pair their skills to attack Professor Epstein's
      analysis. As they have done on several other occasions, Professors Dooley and
      Gaston argue that the kidney donation and transplantation arena is fraught with
      racial inequity, and that Professor Epstein's proposal for a market in kidneys
      will exacerbate this inequity. The authors maintain that to prevent the poor from
      being excluded from transplants, the government plays a critical (if imperfect)
      role in the allocation of these scarce resources. Furthermore, government
      intervention is acceptable to correct past discrimination because there is
      scientific evidence that the disproportionate incidence of kidney failure in
      African Americans is related to the evolutionary pressures of slave trading and
      slavery. Professors Dooley and Gaston also defend their previous efforts to
      change the government system of allocation and characterize the government's
      willingness to adopt their recommendations as an appropriate response to
      scientific research rather than a governmental susceptibility to lobbying from
      special interest groups. Finally, the authors criticize Professor Epstein's
      argument that dialysis is a viable alternative to transplantation because there
      are significant differences in "quality of life, morbidity and survival."
      Professors Dooley and Gaston conclude that government intervention is necessary
      for maintaining the equity in kidney transplantation that a market system would
      not.

PMID- 12071209
TI  - Determining health care rights from behind a veil of ignorance.
AB  - Should our society establish positive rights to health care that each citizen
      could claim, as many health policy analysts believe? Or should it provide only
      background rules of contract and property law and leave the provision of health
      care to the free market, as Richard Epstein advocates in Mortal Peril? In this
      article, Professor Korobkin argues that this question should be addressed from
      the Rawlsian "veil of ignorance" perspective. That is, the question should be
      answered by asking what kind of society would individuals agree to form if they
      had no knowledge of their individual skills or endowments; if they did not know
      whether they were rich or poor, healthy or sick, weak or strong. Professor
      Korobkin contends that individuals behind such a veil of ignorance would balance
      their inherent risk aversion (which favors a safety net of "rights") against the
      inefficient incentives created by rights regimes that would reduce net social
      wealth (which favors a free market). Whether they would choose to establish
      rights to health care or not is ultimately an empirical question that turns on
      how inefficient any particular right would be. The question thus requires a case
      by-case analysis of proposed rights. The article then considers the policy issues
      of (1) community rating of private health insurance and (2) the mandated
      provision of emergency medical care. It concludes that in these cases the
      inefficient incentives created by establishing rights are probably smaller and/or
      controllable enough to lead individuals behind the veil of ignorance to favor a
      regime of positive rights.

PMID- 12071210
TI  - The alleged distinction between euthanasia and the withdrawal of life-sustaining
      treatment: conceptually incoherent and impossible to maintain.
AB  - Richard Epstein, in his book Mortal Peril, supports euthanasia and assisted
      suicide and rejects the distinction between them and withdrawal treatment. In
      this essay, Professor Orentlicher argues that Epstein is correct in finding no
      meaningful moral distinction between euthanasia and treatment withdrawal,
      examines the reasons why the distinction has persisted in American jurisprudence,
      and explains why the distinction has eroded. Epstein also concludes in his book
      that there is no constitutional right to euthanasia or assisted suicide.
      Professor Orentlicher's response is that constitutionality is not the appropriate
      inquiry; rather, the better question is whether to recognize a right to assisted
      suicide once a right to euthanasia in the form of terminal sedation already
      exists. He answers this question in the affirmative, arguing that assisted
      suicide enhances patient welfare and reduces risks of abuse in a world with
      euthanasia.

PMID- 12071211
TI  - Living dangerously: a defense of Mortal Peril.
AB  - As one of the most controversial writers of our time, just the name Richard
      Epstein draws immediate attention from all sectors of academia. But if the
      hallmark of great ideas is the criticism they engender, Professor Epstein's words
      and thoughts are powerful indeed. In Mortal Peril, Professor Epstein outlined a
      fundamental shift in thinking that he claimed needed to occur before any
      discussion of health care could take place. The final consensus of the validity
      of Professor Epstein's views may still be a matter for history to judge, but in
      many ways, he has already won; with the strength of his logic and convictions, he
      has forced other scholars to address his concerns, and in doing so, he has
      refocused the debate on health care. At the symposium, Professor Epstein proved
      his indisputable eloquence and debating skill in answering and refuting the
      various points made by his many critics. Now, in writing, he thoughtfully
      considers and analyzes the views submitted by his colleagues, and solidifies the
      ideas that first found their expression in Mortal Peril.

PMID- 12071212
TI  - Regulating choice: a constitutional law response to Professor John A. Robertson's
      Children of Choice.

PMID- 12071213
TI  - Products of the will: Robertson's Children of Choice.

PMID- 12071214
TI  - Children of Choice: whose children? At what cost?

PMID- 12071215
TI  - Children of Choice: a doctor's perspective.

PMID- 12071216
TI  - Managed care, autonomy, and decisionmaking at the end of life.

PMID- 12071217
TI  - Physicians as advocates.

PMID- 12071218
TI  - Toward a systemic theory of informed consent in managed care.

PMID- 12071219
TI  - HIV, the ADA, and the duty to treat.

PMID- 12071220
TI  - Access to health care for individuals with hearing impairments.

PMID- 12071221
TI  - The Americans with Disabilities Act and managed care.

PMID- 12071222
TI  - "Their promises of paradise": will Olmstead v. L.C. resuscitate the
      constitutional "least restrictive alternative" principle in mental disability
      law?

PMID- 12071223
TI  - Dendrimers.

PMID- 12071224
TI  - Core and periphery functionalized dendrimers for transition metal catalysis; a
      covalent and a non-covalent approach.
AB  - Dendrimers are well-defined hyperbranched macromolecules with characteristic
      globular structures for the larger systems. The recent impressive strides in
      synthetic procedures increased the accessibility of functionalized dendrimers at
      a practicable scale, resulting in a rapid development of dendrimer chemistry.
      Dendrimers have inspired many chemists to develop new materials and several
      applications have been explored, catalysis being one of them. The position of the
      catalytic site(s) as well as the spatial separation of the catalysts within the
      dendritic framework is of crucial importance. Dendrimers that are functionalized
      with transition metals in the core can potentially mimic properties of enzymes,
      their efficient natural counterparts, whereas the surface-functionalized systems
      have been proposed to fill the gap between homogeneous and heterogeneous
      catalysis. We prepared both core- and periphery-functionalized dendritic
      catalysts that are sufficiently large to enable separation by modern
      nanofiltration techniques. Here we review our recent findings using these
      promising novel transition metal-functionalized dendrimers as catalysts in
      several reactions. We will discuss some of the consequences of the
      architecturally different systems that have been studied and will elaborate on a
      novel non-covalent strategy of dendrimer functionalization.

PMID- 12071225
TI  - Dendritic supports in organic synthesis.
AB  - An overview is presented of the recent developments in the use of dendritic
      supports in organic synthesis. Examples are presented of the application of
      dendritic supports in both liquid- and solid-phase organic synthesis. In liquid
      phase synthesis, soluble dendrimers are used as the substrate support, while in
      solid-phase synthesis, 'dendronized' insoluble resins are used for this purpose.
      Selected examples of the synthesis of compound libraries on dendritic supports
      via combinatorial techniques are discussed.

PMID- 12071226
TI  - Peptide dendrimers: applications and synthesis.
AB  - Peptide dendrimers are radial or wedge-like branched macromolecules consisting of
      a peptidyl branching core and/or covalently attached surface functional units.
      The multimeric nature of these constructs, the unambiguous composition and ease
      of production make this type of dendrimer well suited to various biotechnological
      and biochemical applications. Applications include use as biomedical diagnostic
      reagents, protein mimetics, anticancer and antiviral agents, vaccines and drug
      and gene delivery vehicles. This review focuses on the different types of peptide
      dendrimers currently in use and the synthetic methods commonly employed to
      generate peptide dendrimers ranging from stepwise solid-phase synthesis to
      chemoselective and orthogonal ligation.

PMID- 12071227
TI  - Design and synthesis of glycodendrimers.
AB  - Multivalent neoglycoconjugates with well-defined structures have considerable
      potential as inhibitors of cell surface protein-carbohydrate interactions and as
      tools for studying such recognition processes in vitro. In this review, we
      outline strategies and synthetic methods for making one such class of
      neoglycoconjugates based on dendrimers--the so-called glycodendrimers.
      Glycodendrimers can be classified as: (i) carbohydrate-coated; (ii) carbohydrate
      centered; and (iii) fully carbohydrate-based. Approaches to their construction
      have included both the modification of commercially available dendrimers and de
      novo dendrimer synthesis. Examples from the authors' and other laboratories are
      drawn upon to illustrate design considerations and the application of dendritic
      synthetic principles--including divergent and convergent syntheses--for making
      glycodendrimers. Key coupling reactions for the synthesis of glycodendrimers
      include: amide and thiourea formation; glycosylation; photoaddition to allyl
      ethers; and reductive amination. The advantages and disadvantages of using
      protected and unprotected saccharide building blocks and potential applications
      for glycodendrimers in both biotechnology and materials science are also
      discussed.

PMID- 12071228
TI  - Dendritic polyglycerol: a new versatile biocompatible-material.
AB  - Polyglycerol represents the first hyperbranched polymer that can be prepared in a
      controlled synthesis. It is characterized by the combination of a stable,
      biocompatible polyether scaffold, high-end group functionality and a compact,
      well-defined dendrimer-like architecture. These characteristics can be used to
      generate new materials properties and for biomedical applications to molecularly
      amplify or multiply effects or to create extremely high local concentrations of
      drugs, molecular labels, or probe moieties. Therefore, dendritic polyglycerols
      are expected to lead to new strategies for 'molecular medicine'. In this brief
      summary, the current state of the art in polyglycerol research is given, focusing
      on applications in life sciences.

PMID- 12071229
TI  - Design, functional evaluation and biomedical applications of carbohydrate
      dendrimers (glycodendrimers).
AB  - Receptors for carbohydrates of the lectin type are multisubunit and multivalent
      proteins with many important biological functions. In order to put their unique
      biological activities into use in biotechnology and biomedicine, efficient
      carbohydrate ligands of the glycodendrimer type have been constructed. Although
      these compounds may be branched into the multiple generations, structures bearing
      four to 16 terminal carbohydrate substituents have proved to be efficient ligands
      in most lectin systems. These compounds are rapidly finding important practical
      applications as antitumor and antiinfective compounds.

PMID- 12071230
TI  - Glycodendrimers: novel glycotope isosteres unmasking sugar coding. case study
      with T-antigen markers from breast cancer MUC1 glycoprotein.
AB  - Glycodendrimers are relatively novel synthetic biomacromolecules that are made of
      biologically relevant carbohydrate ligands constructed at the periphery of a wide
      range of highly functionalized and repetitive scaffolds having varied molecular
      weights and structures. They were aimed to fill the gap between glycopolymers,
      having generally dispersed higher molecular weight, and small glycoclusters, in
      the study of multivalent carbohydrate protein interactions. In a way,
      glycodendrimers, with their spheroidal or dendritic (wedge) type structures, were
      initially designed as bioisosteres of cell surface multiantennary glycans. Taken
      as a curiosity and elegant molecules at their beginning, they are now considered
      as potent inhibitors of microbial adhesins. They have also been shown to play
      some roles in signal transduction and in receptor cross-linking. This brief
      report will describe advances that have been made toward the syntheses of a range
      of glycodendrimers bearing the immunodominant T-antigen disaccharide [beta-D-Gal
      (1-3)-alpha-D-GalNAc] found on malignant cells of carcinomas, particularly
      related to breast cancer. This antigen, usually cryptic on healthy tissues, is
      greatly increased on cancer cells as a result of aberrant glycosylation. It is
      considered to be an important cancer marker. The high incidence of these
      carcinomas to invade other tissues such as lymph nodes, lung, and liver by
      metastasis was one of the arguments raised to generate T-antigen dendrimers that
      might have the potential to block the receptor sites following surgery. The
      synthesis of the T-antigen disaccharide will be briefly described, followed by
      the elaboration of neoglycoproteins and glycopolymers used to raise monoclonal
      antibodies against the T-antigen and for screening purpose, respectively.
      Scaffolds made of poly(amidoamine) (PAMAM), poly(propylene imine), N,N'
      bis(acrylamido)acetic acid, and finally hyperbranched L-lysine were used to
      construct relatively small glycodendrimers bearing T-antigen moieties. Few
      glycodendrimers were also linked to fluorescein and biotin probes to generate
      ligands that can be used to detect T-Ag receptor sites.

PMID- 12071231
TI  - Molecular dynamics simulations of glycoclusters and glycodendrimers.
AB  - Protein-carbohydrate recognition plays a crucial role in a wide range of
      biological processes, required both for normal physiological functions and the
      onset of disease. Nature uses multivalency in carbohydrate-protein interactions
      as a strategy to overcome the low affinity found for singular binding of an
      individual saccharide epitope to a single carbohydrate recognition domain of a
      lectin. To mimic the complex multi-branched oligosaccharides found in
      glycoconjugates, which form the structural basis of multivalent carbohydrate
      protein interactions, so-called glycoclusters and glycodendrimers have been
      designed to serve as high-affinity ligands of the respective receptor proteins.
      To allow a rational design of glycodendrimer-type molecules with regard to the
      receptor structures involved in carbohydrate recognition, a deeper knowledge of
      the dynamics of such molecules is desirable. Most glycodendrimers have to be
      considered highly flexible molecules with their conformational preferences most
      difficult to elucidate by experimental methods. Longtime molecular dynamics (MD)
      simulations with inclusion of explicit solvent molecules are suited to explore
      the conformational space accessible to glycodendrimers. Here, a detailed
      geometric and conformational analysis of 15 glycodendrimers and glycoclusters has
      been accomplished, which differ with regard to their core moieties, spacer
      characteristics and the type of terminal carbohydrate units. It is shown that the
      accessible conformational space depends strongly on the structural features of
      the core and spacer moieties and even on the type of terminating sugars. The
      obtained knowledge about possible spatial distributions of the sugar epitopes
      exposed on the investigated hyperbranched neoglycoconjugates is detailed for all
      examples and forms important information for the interpretation and prediction of
      affinity data, which can be deduced from biological testing of these multivalent
      neoglycoconjugates.

PMID- 12071232
TI  - Gene transfer into eukaryotic cells using activated polyamidoamine dendrimers.
AB  - The development of efficient methods to transfer genes into eukaryotic cells is
      important for molecular biotechnology. A number of different technologies to
      mediate gene transfer have been developed over the last 35 years, but most have
      drawbacks such as cytotoxicity, low efficiency and/or restricted applicability.
      Activated polyamidoamine (PAMAM)-dendrimers provide a new technology for gene
      transfer that offers significant advantages over classical methods. Reagents
      based on this technology provide high gene transfer efficiencies, minimal
      cytotoxicity, and can be used with a broad range of cell types. This technology
      could also be useful for in vivo gene transfer in gene therapy applications.

PMID- 12071233
TI  - End-of-life decisions in The Netherlands.

PMID- 12071234
TI  - Airway management by physicians wearing anti-chemical warfare gear: comparison
      between laryngeal mask airway and endotracheal intubation.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the ease with which successful insertion of
      a laryngeal mask airway can be performed in comparison with endotracheal
      intubation by medical personnel wearing chemical protective equipment. METHODS:
      Anaesthetists and non-anaesthetists (each n = 20) participated in the prospective
      comparative trial in an animal laboratory. The time and success rates of
      laryngeal mask airway vs. endotracheal tube insertions were measured as performed
      on anaesthetized monkeys. RESULTS: The results showed that the laryngeal mask
      airway was inserted more rapidly than the endotracheal tube by both groups (3.6 s
      and 28.6 s, P < 0.0001). Failed intubation occurred in 35% (anaesthetists) vs.
      55% (non-anaesthetists) (P = 0.17). CONCLUSIONS: In view of the 100% success rate
      of insertion even in unfavourable conditions, the possible role of the laryngeal
      mask airway in the scenario of a toxic mass casualty event should be considered.

PMID- 12071235
TI  - Iontophoretically applied lidocaine and the prevention of pain associated with
      the injection of intravenous propofol: a comparison with intravenous lidocaine.
AB  - BACKGROUND AND OBJECTIVE: Pain following the injection of propofol is a common
      problem. It is often treated by the coadministration of intravenous lidocaine.
      Iontophoresis, which facilitates the delivery of charged molecules such as
      lidocaine to body tissues, may be a practical alternative to lessen the pain.
      METHODS: The iontophoretic application of lidocaine was compared with intravenous
      lidocaine to assess the relative efficacy of reducing pain during propofol
      administration. RESULTS: The incidence rate of moderate or severe pain was
      significantly greater in the iontophoresis group (26.7 compared with 6.9% in the
      intravenous lidocaine group) (P < 0.05). CONCLUSIONS: The iontophoretic
      administration of lidocaine 60 mg does not compare favourably with lidocaine 40
      mg mixed with propofol for the reduction of pain on administration of propofol.

PMID- 12071236
TI  - Ketamine and the inhibition of albumin extravasation in chemical peritonitis in
      rat.
AB  - BACKGROUND AND OBJECTIVE: It was previously reported that topical ketamine
      inhibits albumin extravasation in a rat chemical peritonitis model. Using the
      same model, the present study investigated whether intravenous ketamine inhibited
      this extravasation. METHODS: Twenty-four rats anaesthetized with pentobarbital
      (75 mg kg(-1)) were randomly assigned to two groups: ketamine and a 0.9% NaCl
      (saline) group (n = 12 each). Ketamine 1% or saline 0.1 mL kg(-1) min(-1) was
      given intravenously for 60 min to the respective group. After the abdomen had
      been opened, peritonitis was elicited by topically applying a filter paper
      containing 0.02 M HCl 0.07 mL onto the surface of the appendix or caecum for 5
      min. Fifteen minutes after removal of the filter paper, Evans' blue dye (50 mg
      kg(-1)) was injected intravenously. The extravasated dye was colorimetrically
      quantified by a spectrophotometer at 620 nm. RESULTS: The infusion of ketamine
      significantly reduced Evans' blue extravasation: 5.26 (range 4.18-6.34) microg
      per 100 mg tissue compared with the saline group control: 6.81 (5.93-7.69) microg
      per 100 mg tissue (P < 0.05). CONCLUSIONS: It is suggested that ketamine
      anaesthesia may reduce albumin extravasation in inflammatory tissues.

PMID- 12071237
TI  - Propofol in rats: testing for nonlinear pharmacokinetics and modelling acute
      tolerance to EEG effects.
AB  - BACKGROUND AND OBJECTIVE: Pharmacokinetics of propofol in rats have usually been
      described using linear models. Furthermore, there are only a few investigations
      for a pharmacodynamic model of the electroencephalographic effects of propofol in
      rats. We investigated pharmacokinetics and pharmacodynamics of propofol in rats
      with special regard to linearity in pharmacokinetics and development of
      tolerance. METHODS: Twelve adult male Sprague-Dawley rats received propofol in
      three successive infusion periods of 30 min each with infusion rates of 0.5, 1
      and 0.5 mg kg(-1) min(-1). Propofol plasma concentrations were determined from
      arterial blood samples. Pharmacokinetics were tested for linearity using the
      ratio of the concentrations at the end of the first and second infusion interval
      as a model independent criterion. Several linear and nonlinear models were
      investigated with population pharmacokinetic analysis. Pharmacodynamics were
      analysed using the median frequency of the electroencephalographic power spectrum
      as a quantitative measure of the hypnotic effect. RESULTS: Pharmacokinetics were
      found to be nonlinear and were best described by a two-compartment model with
      Michaelis-Menten elimination (Vm = 2.17 microg mL(-1) min(-1), Km = 2.65 microg
      mL(-1), k12 = 0.30 min(-1), k21 0.063 min(-1), Vc = 0.13 L). Acute tolerance to
      the electroencephalographic effect of propofol was observed. The hypnotic effect
      was best described by a sigmoid Emax model (E0 = 17.8 Hz, Emax = 17.7 Hz, EC50 =
      4.1 microg mL(-1), gamma = 2.3, ke0 = 0.36 min(-1)) with competitive antagonism
      of propofol and a hypothetical drug in an additional tolerance compartment.
      CONCLUSIONS: For the applied infusion scheme, propofol pharmacokinetics in rats
      were nonlinear and a development of tolerance to the electroencephalographic
      effect of propofol was observed during an infusion time of 90 min.

PMID- 12071238
TI  - Subcutaneous epinephrine administration decreases lower oesophageal sphincter
      pressure and gastro-oesophageal pressure gradient in children under general
      anaesthesia.
AB  - BACKGROUND AND OBJECTIVE: Children are vulnerable to regurgitation with a
      relatively high incidence of aspiration during general anaesthesia which is
      attributed to the high intragastric pressure, a short oesophagus, an immature
      laryngeal reflex and incomplete lower oesophageal sphincter muscle function.
      Subcutaneous administration of epinephrine is generally used in surgery to
      decrease bleeding due to local vasoconstriction. The effect of epinephrine on the
      sphincter muscle tone was investigated during general anaesthesia in children.
      METHODS: Ten children scheduled for skin graft or plastic surgery of the ear were
      studied. A gastrointestinal pressure sensor was inserted nasally, and the
      intraluminal pressures of the lower oesophagus, lower oesophageal sphincter and
      stomach were monitored under sevoflurane, nitrous oxide anaesthesia. The effect
      of epinephrine on the lower oesophageal sphincter muscle tone was measured.
      RESULTS: The resting pressure of the lower oesophageal sphincter muscle tone
      significantly decreased from 4.56 +/- 1.85 to 3.79 +/- 1.11 kPa after 3 microg
      kg(-1) epinephrine for 4 min. The barrier pressure is the difference between the
      lower oesophageal sphincter and intragastric pressure, and that decreased to 1.23
      +/- 1.17 kPa from the 2.07 +/- 1.77 kPa resting level. The observations implied
      that epinephrine had a long-lasting relaxing effect on lower oesophageal
      sphincter muscle in children. CONCLUSIONS: The observations may give some
      explanation about the mechanism of gastro-oesophageal reflux during general
      anaesthesia, especially in the participation of the adrenergic receptors.

PMID- 12071239
TI  - Alcohol-associated admissions to an adult intensive care unit: an audit.
AB  - BACKGROUND AND OBJECTIVE: Excessive alcohol consumption is a major cause for
      premature death and preventable ill health in the whole population. We set out to
      audit admissions to the intensive care unit (ICU) of our large teaching hospital
      with respect to alcohol-related admissions. METHODS: A prospective audit was
      conducted into alcohol-associated admissions to our university hospital adult ICU
      over 12 months. The following data were collected for each patient admitted: age,
      gender, diagnosis and amount of alcohol consumption, APACHE II score, and the
      probability of death. RESULTS: Patients with definite alcohol consumption
      constituted 39.1% (124 patients) of all admissions (317 patients) to the ICU. In
      Group 1 (89 patients), the admission was directly associated with alcohol
      consumption, which included heavy alcohol consumption. Group 2 (35 patients)
      consisted of 'social drinkers'; and Group 3 was composed of patients who denied
      any alcohol intake. Group 1 had a high median APACHE II score of 19 (range 4-35)
      and a significantly higher mortality rate (41.6%) than Group 3 (18.4%, P < 0.001)
      or the entire sample studied (23.7%, P < 0.001). The results also demonstrated an
      incidence of pneumonia of 29.2% (26 patients) in alcohol-associated admissions
      compared with 22.8% (eight patients) in Group 2 and 21.8% (19 patients) in Group
      3. Trauma admissions amounted to 11.4% of the patients studied (24/211 patients),
      17 (70.8%) of whom were directly associated with alcohol and it included 11
      pedestrians. CONCLUSIONS: Alcohol may play a major role in the admission and
      mortality of ICU patients. Further investigations are warranted because our
      sample size is so small.

PMID- 12071240
TI  - Bilateral paravertebral somatic nerve block for ventral hernia repair.
AB  - BACKGROUND AND OBJECTIVE: Unilateral paravertebral nerve blockade has been
      reported to produce excellent afferent nerve block, reduce the incidence of
      postoperative nausea and vomiting, and reduce hospital stay following inguinal
      hernia repair. The aim was to compare the use of bilateral paravertebral blocks
      to regular general anaesthesia for ventral hernia repair. METHODS: Sixty patients
      were prospectively allocated to receive either bilateral paravertebral nerve
      blockade (midazolam for block; supplemented with light intraoperative sedation if
      needed) or general anaesthesia for ventral hernia repair. The end-points of the
      study were length of hospital stay, postoperative analgesia (visual analogue
      scale, supplemental opioid requirement) and incidence of postoperative nausea and
      vomiting. RESULTS: The duration of hospital stay was observed to be shorter in
      patients handled with bilateral paravertebral nerve blockade (2.3 [SD 1.3] days)
      compared with patients receiving general anaesthesia (4.1 (3.0) days).
      Paravertebral analgesia resulted in both lower visual analogue scores and a
      significantly reduced need for supplemental opioid administration during the
      first 48 h postoperatively compared with general anaesthesia (P < 0.001). The
      rate of postoperative nausea and vomiting in the paravertebral nerve blockade
      group was only 3.3%, while 26.7% of patients in the general anaesthesia group
      suffered from postoperative nausea and vomiting (P < 0.05). Paravertebral nerve
      blockade was associated with good patient acceptance in 90% of patients.
      CONCLUSIONS: Bilateral paravertebral blockade combined with light intravenous
      sedation was superior to general anaesthesia for ventral hernia repair.
      Paravertebral blockade was associated with shorter hospital stay, improved
      analgesia and less postoperative nausea and vomiting. It is suggested that this
      technique deserves more widespread use in patients undergoing ventral hernia
      repair.

PMID- 12071241
TI  - Cuffed oropharyngeal airway as a suitable alternative to the laryngeal mask
      airway for minor outpatient surgery.
AB  - BACKGROUND AND OBJECTIVE: To compare the application of the cuffed oropharyngeal
      airway and the laryngeal mask airway on anaesthetized adult patients undergoing
      minor outpatient surgery. METHODS: One hundred patients received intravenous
      fentanyl, propofol and N20 for the induction and maintenance of anaesthesia. The
      patients were randomly divided into two groups: a cuffed oropharyngeal airway
      group (n = 50) and a laryngeal mask airway group (n = 50). After insertion of the
      device, fibreoptic laryngoscopy was attempted and the degree of success scored.
      We then compared the first application success rate of both procedures while
      judging airway intervention requirement, fibreoptic scores, adverse airway events
      and haemodynamic tolerance. RESULTS: Both devices had an almost similar first
      time placement rate (cuffed oropharyngeal airway 84% versus laryngeal mask airway
      96%). The cuffed oropharyngeal airway required a higher number of airway
      interventions (P < 0.001). The laryngeal mask airway had a significantly better
      fibreoptic view compared with the cuffed oropharyngeal airway (P < 0.001).
      However, the number of adverse airway events was lower in the cuffed
      oropharyngeal airway group; there were no significant differences in adverse
      events and haemodynamic variables between the said two groups. CONCLUSIONS: The
      results suggest that the cuffed oropharyngeal airway was an effective alternative
      airway in spontaneously breathing patients during short procedures.

PMID- 12071242
TI  - Use of hyperbaric oxygen for hepatic artery thrombosis following adult orthotopic
      liver transplantation.

PMID- 12071244
TI  - Multicompartment block in a parturient undergoing urgent Caesarean section.

PMID- 12071243
TI  - Venous gas embolism during liver surgery with argon-enhanced coagulation.

PMID- 12071245
TI  - Minor haemodynamic responses in coronary bypass patients following tracheal
      intubation using either a lightwand device (Trachlight) or direct laryngoscopy.

PMID- 12071246
TI  - Software sensor for on-line estimation of the microbial activity in activated
      sludge systems.
AB  - This paper considers the design of a software sensor (or soft-sensor) for the on
      line estimation of the biological activities of a colony of aerobic micro
      organisms acting on activated sludge processes, where the carbonaceous waste
      degradation and nitrification processes are taken into account. These
      bioactivities are intimately related to the dissolved oxygen concentration. Two
      factors that affect the dynamics of the dissolved oxygen are the respiration rate
      or the oxygen uptake rate (OUR) and the oxygen transfer function (K(l)a). These
      items are challenging topics for the application of recursive identification due
      the nonlinear characteristic of the oxygen transfer function, and to the time
      varying feature of the respiration rate. In this work, OUR and the oxygen
      transfer function are estimated through a software sensor, which is based on a
      modified version of the discrete extended Kalman filter. Numerical simulations
      are carried out in a predenitrifying activated sludge process benchmark and the
      obtained results demonstrate the applicability and efficiency of the proposed
      methodology, which should provide a valuable tool to supervise and control
      activated sludge processes.

PMID- 12071247
TI  - High frequency testing of rubber mounts.
AB  - Rubber and fluid-filled rubber engine mounts are commonly used in automotive and
      aerospace applications to provide reduced cabin noise and vibration, and/or
      motion accommodations. In certain applications, the rubber mount may operate at
      frequencies as high as 5000 Hz. Therefore, dynamic stiffness of the mount needs
      to be known in this frequency range. Commercial high frequency test machines are
      practically nonexistent, and the best high frequency test machine on the market
      is only capable of frequencies as high as 1000 Hz. In this paper, a high
      frequency test machine is described that allows test engineers to study the high
      frequency performance of rubber mounts at frequencies up to 5000 Hz.

PMID- 12071248
TI  - Detection of abrupt change and applications in sensor decalibration monitoring.
AB  - The primary objective of fault detection is to detect abrupt undesirable changes
      in a process at an early stage. This early detection has a potential of
      preventing loss of production and equipment damage due to these undesirable
      changes, thus reducing process downtime. This paper details the implementation of
      some parametric fault detection techniques for sensor decalibration monitoring. A
      parametric fault detection approach that is handled in depth in this paper is the
      local approach. This approach developed by Benveniste, Basseville, and
      Moustakides [Benveniste, A., Basseville, M., and Moustakides, G., The asymptotic
      local approach to change detection and model validation. IEEE Trans. Autom.
      Control AC-32 (7), 583-592 (1987)] offers a computationally inexpensive way to
      attain the objective of monitoring changes in model parameters. However, the
      algorithm in its original formulation is not applicable to certain processes such
      as sensors. Therefore, the local approach is coupled with other estimation
      algorithms such as the input independent Kalman filter to derive a robust sensor
      decalibration monitoring algorithm. The proposed fault detection algorithm is
      applied to a pilot scale process for evaluation of its performance.

PMID- 12071249
TI  - A statistically based filter.
AB  - A simple procedure is developed that uses concepts from statistical process
      control to filter noise from a process variable. Code is presented for the
      algorithm, and it is experimentally demonstrated on a pilot-scale process for
      which both noise and level change significantly and frequently.

PMID- 12071250
TI  - From linear to nonlinear control means: a practical progression.
AB  - With the rapid advance of digital control hardware, it is time to take the simple
      but effective proportional-integral-derivative (PID) control technology to the
      next level of performance and robustness. For this purpose, a nonlinear PID and
      active disturbance rejection framework are introduced in this paper. It
      complements the existing theory in that (1) it actively and systematically
      explores the use of nonlinear control mechanisms for better performance, even for
      linear plants; (2) it represents a control strategy that is rather independent of
      mathematical models of the plants, thus achieving inherent robustness and
      reducing design complexity. Stability analysis, as well as software/hardware test
      results, are presented. It is evident that the proposed framework lends itself
      well in seeking innovative solutions to practical problems while maintaining the
      simplicity and the intuitiveness of the existing technology.

PMID- 12071251
TI  - Robustness of discrete-time state feedback control systems.
AB  - This paper presents stability robustness results for linear multivariable
      discrete-time systems with uncertainties. Robust stability of the full-state
      feedback linear quadratic regulator in the presence of perturbations of the
      system parameters is investigated. These results are based on recently developed
      bounds on structured perturbations of a stable linear discrete-time system. The
      paper applies these results to a paper-machine head box system example.

PMID- 12071252
TI  - Grouped-neural network modeling for model predictive control.
AB  - A group of feed-forward neural networks (NNs), each providing the prediction of
      an individual process output at a future step, is used as the dynamic prediction
      model for the model-based predictive control (MPC) scheme in the proposed work.
      These NNs are parallel (independent) rather than cascaded--they are trained and
      implemented in parallel. Therefore, the complexity and effort in the training
      stage is decreased and compounded error propagation is eliminated from the
      prediction. A new strategy of compensating for the process-model mismatch under
      this grouped-NN model structure is also developed. Effectiveness of the scheme as
      a general nonlinear MPC is demonstrated by simulation results.

PMID- 12071253
TI  - Experimental investigation of subspace identification and LQ control of a
      pressure tank.
AB  - Many control studies of complex processes are limited to simulation studies.
      However, many real processes exhibit peculiarities and nonlinearities that are
      difficult to model. Also some control designs are difficult to implement online
      in practice. Because of the recent availability of economical real time software,
      more complex control algorithms will see real time testing and implementation. In
      spite of this, many compromises are often necessary when the final control is
      implemented. This paper follows the identification (using subspace methods) and
      real time linear quadratic control of a pressure tank system and points to some
      of the compromises in identification and control design that are often necessary.
      A multivariate control is implemented on a pressure tank process with rather good
      results in spite of these compromises.

PMID- 12071254
TI  - A study of control strategy for the bin system with tube mill in the coal fired
      power station.
AB  - The pulverized coal systems with tube mills are widely used in coal fired power
      plants. As there are many controlled variables and disturbances in this system,
      and startup and shutdown of the system is frequent and the dynamic characteristic
      of the controlled plant is also extraordinary, the automatic control system for
      this kind of pulverized coal system is not ideally implemented for long. The
      authors of this paper investigated and tested a pulverized coal system with tube
      mill in Nanjing Thermal Power Station, and based on various different controlled
      plants and control objectives, proposed rather independent control subsystems.
      These subsystems can organize a whole automatic control system of pulverized coal
      system that can be used in different conditions. The control system presented in
      this paper has worked well since it was put into operation in May 1998, and good
      economic benefits have been acquired.

PMID- 12071255
TI  - Identification and robust control of an experimental servo motor.
AB  - In this work, the design of a robust controller for an experimental laboratory
      scale position control system based on a dc motor drive as well as the
      corresponding identification and robust stability analysis are presented. In
      order to carry out the robust design procedure, first, a classic closed-loop
      identification technique is applied and then, the parametrization by internal
      model control is used. The model uncertainty is evaluated under both parametric
      and global representation. For the latter case, an interesting discussion about
      the conservativeness of this description is presented by means of a comparison
      between the uncertainty disk and the critical perturbation radius approaches.
      Finally, conclusions about the performance of the experimental system with the
      robust controller are discussed using comparative graphics of the controlled
      variable and the Nyquist stability margin as a robustness measurement.

PMID- 12071256
TI  - A fuzzy-logic antiswing controller for three-dimensional overhead cranes.
AB  - In this paper, a new fuzzy antiswing control scheme is proposed for a three
      dimensional overhead crane. The proposed control consists of a position servo
      control and a fuzzy-logic control. The position servo control is used to control
      crane position and rope length, and the fuzzy-logic control is used to suppress
      load swing. The proposed control guarantees not only prompt suppression of load
      swing but also accurate control of crane position and rope length for
      simultaneous travel, traverse, and hoisting motions of the crane. Furthermore,
      the proposed control provides practical gain tuning criteria for easy
      application. The effectiveness of the proposed control is shown by experiments
      with a three-dimensional prototype overhead crane.

PMID- 12071257
TI  - Batch control system project for a pharmaceutical plant.
AB  - This paper describes a case study of a control system design for a batch
      pharmaceutical process. The ISA standard S88.01 batch control models and
      terminology were used as the main guidelines for the implementation. As the S88
      is not a guide for how to apply the definitions/structures, etc., one of the main
      goals of our work was to create a methodology for decomposition of functional
      requirements in terms of S88 models and structures. This methodology was tested
      on a real problem, described in the case study. Also presented are some remarks
      on project methodology and Food and Drug Administration validation.

PMID- 12071259
TI  - Workflow management with systems approach: anticipated and ad-hoc workflow for
      scientific applications [ISA Trans. 39, 153-167 (2000)].

PMID- 12071258
TI  - An intelligent system for multivariate statistical process monitoring and
      diagnosis.
AB  - A knowledge-based system (KBS) was designed for automated system identification,
      process monitoring, and diagnosis of sensor faults. The real-time KBS consists of
      a supervisory system using G2 KBS development software linked with external
      statistical modules for system identification and sensor fault diagnosis. The
      various statistical techniques were prototyped in MATLAB, converted to ANSI C
      code, and linked with the G2 Standard Interface. The KBS automatically performs
      all operations of data collection, identification, monitoring, and sensor fault
      diagnosis with little or no input from the user. Navigation throughout the KBS is
      via menu buttons on each user-accessible screen. Selected process variables are
      displayed on charts showing the history of the variables over a period of time.
      Multivariate statistical tests and contribution plots are also shown graphically.
      The KBS was evaluated using simulation studies with a polymerization reactor
      through a nonlinear dynamic model. Both normal operation conditions as well as
      conditions of process disturbances were observed to evaluate the KBS performance.
      Specific user-defined disturbances were added to the simulation, and the KBS
      correctly diagnosed both process and sensor faults when present.

PMID- 12071260
TI  - Application of type synthesis theory to the redesign of a complex surgical
      instrument.
AB  - Surgical instruments consist of basic mechanical components such as gears, links,
      pivots, sliders, etc., which are common in mechanical design. This paper
      describes the application of a method in the analysis and design of complex
      surgical instruments such as those employed in laparoscopic surgery. This is
      believed to be the first application of type synthesis theory to a complex
      medical instrument. Type synthesis is a methodology that can be applied during
      the conceptual phase of mechanical design. A handle assembly from a patented
      laparoscopic surgical stapler is used to illustrate the application of the design
      method developed. Type synthesis is applied on specific subsystems of the
      mechanism within the handle assembly where alternative design concepts are
      generated. Chosen concepts are then combined to form a new conceptual design for
      the handle assembly. The new handle assembly is improved because it has fewer
      number of parts, is a simpler design and is easier to assemble. Surgical
      instrument designers may use the methodology presented here to analyze the
      mechanical subsystems within complex instruments and to create new options that
      may offer improvements to the original design.

PMID- 12071261
TI  - A finite element model of the human knee joint for the study of tibio-femoral
      contact.
AB  - As a step towards developing a finite element model of the knee that can be used
      to study how the variables associated with a meniscal replacement affect tibio
      femoral contact, the goals of this study were 1) to develop a geometrically
      accurate three-dimensional solid model of the knee joint with special attention
      given to the menisci and articular cartilage, 2) to determine to what extent bony
      deformations affect contact behavior, and 3) to determine whether constraining
      rotations other than flexion/extension affects the contact behavior of the joint
      during compressive loading. The model included both the cortical and trabecular
      bone of the femur and tibia, articular cartilage of the femoral condyles and
      tibial plateau, both the medial and lateral menisci with their horn attachments,
      the transverse ligament, the anterior cruciate ligament, and the medial
      collateral ligament. The solid models for the menisci and articular cartilage
      were created from surface scans provided by a noncontacting, laser-based, three
      dimensional coordinate digitizing system with an root mean squared error (RMSE)
      of less than 8 microns. Solid models of both the tibia and femur were created
      from CT images, except for the most proximal surface of the tibia and most distal
      surface of the femur which were created with the three-dimensional coordinate
      digitizing system. The constitutive relation of the menisci treated the tissue as
      transversely isotropic and linearly elastic. Under the application of an 800 N
      compressive load at 0 degrees of flexion, six contact variables in each
      compartment (ie., medial and lateral) were computed including maximum pressure,
      mean pressure, contact area, total contact force, and coordinates of the center
      of pressure. Convergence of the finite element solution was studied using three
      mesh sizes ranging from an average element size of 5 mm by 5 mm to 1 mm by 1 mm.
      The solution was considered converged for an average element size of 2 mm by 2
      mm. Using this mesh size, finite element solutions for rigid versus deformable
      bones indicated that none of the contact variables changed by more than 2% when
      the femur and tibia were treated as rigid. However, differences in contact
      variables as large as 19% occurred when rotations other than flexion/extension
      were constrained. The largest difference was in the maximum pressure. Among the
      principal conclusions of the study are that accurate finite element solutions of
      tibio-femoral contact behavior can be obtained by treating the bones as rigid.
      However, unrealistic constraints on rotations other than flexion/extension can
      result in relatively large errors in contact variables.

PMID- 12071262
TI  - A biomechanical model of the foot: the role of muscles, tendons, and ligaments.
AB  - A biomechanical model of the foot is developed and analyzed to determine the
      distribution of support under the metatarsal heads, the tension in the plantar
      aponeurosis, and the bending moment at each of the joints of the foot. This model
      is an extension of our earlier work to include the role of muscles, tendons, and
      ligaments. Two cases are presented: in the first the center of gravity of the
      body is over the mid foot, and in the second, the center of gravity is anterior,
      over the metatarsals, and no support is provided by the heel. The model shows the
      extent to which the muscles reduce the force in the supporting ligaments at each
      of the joints and decrease the tension in the plantar aponeurosis, and that this
      effect is more pronounced when the center of gravity of the body is moved
      forward.

PMID- 12071263
TI  - Noninvasive measurement of time-varying three-dimensional relative pressure
      fields within the human heart.
AB  - Understanding cardiac blood flow patterns is important in the assessment of
      cardiovascular function. Three-dimensional flow and relative pressure fields
      within the human left ventricle are demonstrated by combining velocity
      measurements with computational fluid mechanics methods. The velocity field
      throughout the left atrium and ventricle of a normal human heart is measured
      using time-resolved three-dimensional phase-contrast MRI. Subsequently, the time
      resolved three-dimensional relative pressure is calculated from this velocity
      field using the pressure Poisson equation. Noninvasive simultaneous assessment of
      cardiac pressure and flow phenomena is an important new tool for studying cardiac
      fluid dynamics.

PMID- 12071264
TI  - A modeling study of partial ACL injury: simulated KT-2000 arthrometer tests.
AB  - A partial ACL injury may involve different levels of fiber disruption, orfibers
      may sustain microscopic changes in their structure without gross disruption,
      resulting in a change in ligament function. The effect of partial ACL tears on
      the mechanical and functional stability of the knee has not been well documented,
      in part because of diagnostic difficulties. A computer model of the knee in the
      sagittal plane was used in this study to simulate tests using the KT-2000 Knee
      Arthrometer, which quantifies Lachman's test for ACL injury. A variety of partial
      ACL anterior and posterior bundle injuries were simulated. Anterior and posterior
      bundle injuries were subdivided into four different simulated injury levels: mild
      (one-half tear of the bundle), moderate (complete tear of the bundle), severe
      (complete tear of the bundle and tear of one-half of the other bundle), and more
      severe (severe injury plus an additional elongation of the other bundle
      represented by 5% increases of its initial strain). Force-displacement results
      obtained from simulated KT-2000 knee arthrometer tests depended on the level of
      injury. Mild and moderate injuries produced only small change in the anterior
      tibial translation--at different force levels. Severe injury produced increased
      anterior tibial translation depending on which bundle was completely ruptured.
      The compliance index defined as the ratio of the displacement and the force
      within 68 N and 90 N anterior drawer forces, the stiffness, and the rate of
      change of stiffness of the anterior force-displacement were found to be better at
      predicting partial ACL ruptures than simple differences in anterior tibial
      translation. It was possible in the model results to discriminate knees with
      various levels of partial ACL injuries using the first and second derivatives of
      the force-displacement curve.

PMID- 12071265
TI  - Measurement of distribution of maximum index-fingertip force in all directions at
      fingertip in flexion/extension plane.
AB  - The purpose of the present study is to investigate whether distribution patterns
      of the maximum fingertip force in all directions from 0 deg to 360 deg around the
      index fingertip are the same among subjects. Distributions of the maximum index
      fingertip force were measured at four finger postures for five subjects (healthy
      males, ages 21 to 25). It became apparent that distribution patterns of the
      fingertip force were very similar among subjects, through the application of an
      analysis of variance (level of significance: 5%) to the measurement results. In
      the production of the maximum fingertip force, Valero-Cuevas et al. [1998, 2000]
      reported that patterns of control signals for driving muscle forces were common
      among subjects. The results of the present study indicate that patterns of
      maximum fingertip force are also similar among subjects. Therefore, the
      possibility is high that the static transfer characteristic for index fingers
      from input (i.e., control signals to muscles) to output (ie., the maximum
      fingertip force) is also common among subjects.

PMID- 12071266
TI  - Effects of cyclic pressure on bone marrow cell cultures.
AB  - The present in-vitro study used bone marrow cell cultures and investigated the
      effects of cyclic pressure on osteoclastic bone resorption. Compared to control
      (cells maintained under static conditions), the number of tartrate resistant acid
      phosphatase (TRAP)-positive, osteoclastic cells was significantly (p<0.05) lower
      when, immediately upon harvesting, bone marrow cells were exposed to cyclic
      pressure (10-40 kPa at 1.0 Hz). In contrast, once precursors in bone marrow cells
      differentiated into osteoclastic cells under static culture conditions for 7
      days, subsequent exposure to the cyclic pressure of interest to the present study
      did not affect the number of osteoclastic cells. Most important, exposure of bone
      marrow cells to cyclic pressure for 1 h daily for 7 consecutive days resulted in
      significantly (p<0.05) lower osteoclastic bone resorption and in lowered mRNA
      expression for interleukin-1 (IL-1) and tumor necrosisfactor-a (TNF-a), cytokines
      that are known activators of osteoclast function. In addition to unique
      contributions to osteoclast physiology, the present study provided new evidence
      of a correlation between mechanical loading and bone homeostasis as well as
      insight into the molecular mechanisms of bone adaptation to mechanical loading,
      namely cytokine-mediated control of osteoclast functions.

PMID- 12071267
TI  - Experimental and biphasic FEM determinations of the material properties and
      hydraulic permeability of the meniscus in tension.
AB  - Tensile tests and biphasic finite element modeling were used to determine a set
      of transversely isotropic properties for the meniscus, including the hydraulic
      permeability coefficients and solid matrix properties. Stress-relaxation tests
      were conducted on planar samples of canine meniscus samples of different
      orientations, and the solid matrix properties were determined from equilibrium
      data. A 3-D linear biphasic and tranversely isotropic finite element model was
      developed to model the stress-relaxation behavior of the samples in tension, and
      optimization was used to determine the permeability coefficients, k1 and k2,
      governing fluid flow parallel and perpendicular to the collagen fibers,
      respectively. The collagen fibrillar orientation was observed to have an effect
      on the Young's moduli (E1=67.8 MPa, E2=11.1 MPa) and Poisson's ratios (v12=2.13,
      v21 =1.50, v23=1.02). However, a significant effect of anisotropy on permeability
      was not detected (k1 =0.09x10(-16) m4/Ns, k2=0.10x10(-16) m4/Ns). The low
      permeability values determined in this study provide insight into the extent of
      fluid pressurization in the meniscus and will impact modeling predictions of load
      support in the meniscus.

PMID- 12071268
TI  - Damaged-bone adaptation under steady homogeneous stress.
AB  - In this work an extension of the adaptive-elasticity theory is proposed in order
      to include the contribution of bone microdamage as a stimulus. Some aspects of
      damaged-bone tissue adaptation, brought about by a change of the daily loading
      history, are investigated. In particular, under the assumption of a small strain
      approximation and isothermal conditions, the solution of the remodeling rate
      equation for steady homogeneous stress is discussed and the damage effect upon
      the remodeling time constant is shown. The result is both theoretical and
      numerical, based on a recent theory of internal damaged-bone remodeling (Ramtani,
      S., and Zidi, M., 1999, "Damaged-Bone Remodeling Theory: Thermodynamical
      Approach, " Mechanics Research Communications, Vol. 26, pp. 701-708. Ramtani, S.,
      and Zidi, M., 2001, "A Theoretical Model of the Effect of Continum Damage on a
      Bone Adaption Model," Journal of Biomechanics, Vol. 34, pp. 471-479) and
      motivated by the works of Cowin, S. C., and Hegedus, D. M., 1976, "Bone
      Remodeling I: Theory and Adaptive Elasticity," Journal of Elasticity, Vol. 6, pp.
      471-479 and Hegedus, D. H., and Cowin, S. C., 1976, "Bone Remodeling II: Small
      Strain Adaptive Elasticity," Journal of Elasticity, Vol. 6, pp. 337-352.

PMID- 12071269
TI  - End-of-life treatment decisions in long-term care.

PMID- 12071270
TI  - Decreasing aggressive, agitated, or disruptive behavior: perticipation in a
      behavior management unit.
AB  - A 32-bed Behavior Management Unit was opened in a long-term care facility to care
      for dementia patients who exhibit aggressive, agitated, or disruptive (AAD)
      behaviors. The purpose of the study was to evaluate the effectiveness of the
      Behavior Management Program (BMP) in decreasing such behaviors. The sample
      consisted of all patients (N = 32) who resided in the unit for at least 3 months.
      The Nursing Home Behavior Problem Scale (NHBPS) was used to collect data.
      Hypothesis 1, predicting participation in the BMP would decrease the total number
      of AAD behaviors was supported, with a significant decrease from the baseline to
      6-month measurements. Hypothesis 2, predicting participation in the BMP would
      decrease the frequency of occurrence of specific AAD behaviors was supported,
      with 7 behaviors being significantly reduced by 6 months. Nurses in long-term
      care often treat patients with AAD behavior. Because staff members on general
      long-term care units and even in dementia units may not be experts in caring for
      patients with AAD behaviors, the implications of this study might be helpful. The
      interventions that were effective in reducing AAD behaviors included verbal
      distraction, time-outs, activity diversion, getting to know the patient well, and
      managing the environment.

PMID- 12071271
TI  - Burnout: nothing to laugh at.

PMID- 12071272
TI  - Synergism of frail rural elderly couples: influencing interdependent
      independence.
AB  - In this phenomenological study, a purposive sample of 19 frail rural elderly
      couples were interviewed as dyads to identify programs, services, and
      relationships perceived by the couples as beneficial to their ability to continue
      to live independently in the community. Communication between the partners, and
      roles and relationships were observed and discussed. Findings showed that
      mutually supportive dyads generated a synergism or energy that acted as a vital
      resource to couples. Research results led to the development of a continuum of
      spousal relationships and a trajectory of couple communication. Support to the
      couple as a unit, to the couple relationship, and to address the couple's needs
      may be strategic foci for nurses in their delivery of care and their involvement
      in planning programs and developing policy.

PMID- 12071273
TI  - Testing the effect of the WALC intervention on exercise adherence in older
      adults.
AB  - The purpose of this study was to test the feasibility of the WALC intervention
      (Walk; Address pain, fear, fatigue during exercise; Learn about exercise; Cue by
      self-modeling), and determine its effects on self-efficacy and outcome
      expectations, exercise activity and free living activity, physical and mental
      health status, and falls and fall-related injuries. A total of 17 sedentary older
      women with a mean age of 88 +/- 3.7 years were randomly assigned to receive
      either the WALC intervention or routine care. Ninety percent of those in the
      treatment group initiated and engaged in a regular exercise program during the 6
      months of the study. There was a statistically significant difference in self
      efficacy expectations, exercise behavior, and overall activity between the two
      groups. Those in the treatment group had stronger self-efficacy expectations
      related to exercise; engaged in more exercise and more free living activity; and
      although not statistically significant, had stronger outcome expectations
      following exposure to the WALC intervention when compared with those who received
      routine care. To help older adults initiate and adhere to an exercise program,
      nurses can easily implement the WALC intervention in a variety of settings.

PMID- 12071276
TI  - Comprehensive geriatric assessment: exploring clients' and caregivers'
      perceptions of the assessment process and outcomes.

PMID- 12071274
TI  - Have you had your moss today?

PMID- 12071277
TI  - Developing a methodology for an inverse quantitative structure-activity
      relationship using the signature molecular descriptor.
AB  - The concept of signature as a molecular descriptor is introduced and various
      topological indices used in quantitative structure-activity relationships (QSARs)
      are expressed as functions of the new descriptor. The effectiveness of signature
      versus commonly used descriptors in QSAR analysis is demonstrated by correlating
      the activities of 121 HIV-1 protease inhibitors. Our approach to the inverse-QSAR
      problem consists of first finding the optimum sets of descriptor values best
      matching a target activity and then generating a focused library of candidate
      structures from the solution set of descriptor values. Both steps are facilitated
      by the use of signature.

PMID- 12071278
TI  - Methods for compound selection focused on hits and application in drug discovery.
AB  - In the context of virtual screening calculations, a multiple fingerprint-based
      metric is applied to generate focused compound libraries by database searching.
      Different fingerprints are used to facilitate a similarity step for database
      mining, followed by a diversity step to assemble the final library. The method is
      applied, for example, to build libraries of limited size for hit-to-lead
      development efforts. In studies designed to inhibit a therapeutically relevant
      protein-protein interaction, small molecular hits were initially obtained by
      combined fingerprint- and structure-based virtual screening and used for the
      design of focused libraries. We review the applied virtual screening approach and
      report the statistics and results of screening as well as focused library design.
      While the structures of lead compounds cannot be disclosed, the analysis is
      thought to provide an example of the interplay of different methods applied in
      practical lead identification.

PMID- 12071279
TI  - Dbtop: topomer similarity searching of conventional structure databases.
AB  - A new topomer-based method for 3D searching of conventional structural databases
      is described, according to which 3D molecular structures are compared as sets of
      fragments or topomers, in single rule-generated conformations oriented by
      superposition of their fragmentation bonds. A topomer is characterized by its
      CoMFA-like steric shape and now also by its pharmacophoric features, in some
      novel ways that are detailed and discussed. To illustrate the behavior of topomer
      similarity searching, a new dbtop program was used to generate a topomer distance
      matrix for a diverse set of 26 PDE4 inhibitors and 15 serotonin receptor
      modulators. With the best of three parameter settings tried, within the 210
      shortest topomer distances (of 1460), 94.7% involved pairs of compounds having
      the same biological activity, and the nearest neighbor to every compound also
      shared its activity. The standard similarity metric, Tanimoto coefficients of "2D
      fingerprints", could achieve a similar selectivity performance only for the 108
      shortest distances, and three Tanimoto nearest neighbors had a different
      biological activity. Topomer similarity also allowed "lead-hopping" among 22 of
      the 26 PDE4 inhibitors, notably between rolipram and cipamfylline, while 2D
      fingerprints" Tanimotos recognized similarity only within generally recognized
      structural classes. In 370 searches of authentic high-throughput screening (HTS)
      data sets, the typical topomer similarity search rate was about 200 structures
      per s.

PMID- 12071280
TI  - Structure-based combinatorial library design: methodologies and applications.
AB  - Rational design of small focused libraries that are biased toward specific
      therapeutic targets is currently at the forefront of combinatorial library
      design. Various structure-based design strategies can be implemented in focused
      library design when the 3D structure of the target is available through X-ray or
      NMR determination. This review discusses the major methods and programs
      specifically developed for the purpose of designing combinatorial libraries under
      the constraint of the binding site of a biological target, with emphasis on their
      advantages and disadvantages. Examples of the successful application of these
      methodologies are highlighted, demonstrating their performances within the
      practical drug discovery process.

PMID- 12071282
TI  - Subcellular pharmacokinetics and its potential for library focusing.
AB  - Subcellular pharmacokinetics (SP) optimizes biology-related factors in the design
      of libraries for high throughput screening by defining comparatively narrow
      ranges of properties (lipophilicity, amphiphilicity, acidity, reactivity, 3D
      structural features) of the included compounds. The focusing ensures appropriate
      absorption, distribution, metabolism, excretion, and toxicity (ADMET) in those
      test biosystems, which are more complex than isolated receptors, and in humans.
      The SP deploys conceptual models that include transport and accumulation in a
      series of membranes, protein binding, hydrolysis, and other reactions with cell
      constituents. The kinetics of drug disposition is described as a non-linear
      disposition function of drug structure and properties. The SP capabilities are
      illustrated here using a model-based quantitative structure-activity relationship
      of toxicity of phenolic compounds against Tetrahymena pyriformis as dependent on
      lipophilicity and acidity. The resulting SP models clearly outperform empirical
      models in predictive ability outside the parameter space, as revealed by the
      leave-extremes-out cross-validation technique with omission of compounds beyond
      pre-defined lipophilicity and acidity ranges. The SP models do not change
      substantially if the parameters space is shrunk within some limits. In contrast,
      the shapes of empirical models vary widely depending upon the fraction of the
      data set used for their optimization. Once calibrated for a given biosystem, the
      SP models provide a detailed recipe for tailoring the drug properties to ensure
      optimum ADMET. The focusing is more accurate than with traditional empirical QSAR
      studies, assessment of drug-likeness, or the rules for identification of
      compounds with permeability problems.

PMID- 12071281
TI  - Coupling structure-based design with combinatorial chemistry: application of
      active site derived pharmacophores with informative library design.
AB  - Protein structural information is combined with combinatorial library design in
      the following protocol. Active site maps are generated from protein structures.
      All possible 2-, 3- and 4-point pharmacophores are enumerated from the active
      site map and encoded as bit strings. The pharmacophores define a design space
      that can be used to select compounds using an informative library design tool.
      The method was evaluated against a collection of compounds assayed previously
      against a cyclin-dependent kinase target, CDK-2, starting with 23 X-ray co
      crystal structures. Performance was assessed based on the number of active
      scaffolds selected after four rounds of iterative informative library design. The
      method selects compounds from 12 out of the 15 active scaffolds from the CDK-2
      library and outperforms a two-dimensional similarity search and docking
      calculations.

PMID- 12071283
TI  - Designing focused libraries using MoSELECT.
AB  - When designing a combinatorial library it is usually desirable to optimise
      multiple properties of the library simultaneously and often the properties are in
      competition with one another. For example, a library that is designed to be
      focused around a given target molecule should ideally have minimum cost and also
      contain molecules that are bioavailable. In this paper, we describe the program
      MoSELECT for multiobjective library design that is based on a multiobjective
      genetic algorithm (MOGA). MoSELECT searches the product-space of a virtual
      combinatorial library to generate a family of equivalent solutions where each
      solution represents a combinatorial subset of the virtual library optimised over
      multiple objectives. The family of solutions allows the relationships between the
      objectives to be explored and thus enables the library designer to make an
      informed choice on an appropriate compromise solution. Experiments are reported
      where MoSELECT has been applied to the design of various focused libraries.

PMID- 12071284
TI  - Differential laws of left ventricular isovolumic pressure fall.
AB  - An attempt has been made to test for a reliable method of characterizing the
      isovolumic left ventricular pressure fall in isolated ejecting hearts by one or
      two time constants, tau. Alternative nonlinear regression models (three- and four
      parametric exponential, logistic, and power function), based upon the common
      differential law dp(t)/dt = - [p(t)-P ]/ tau(t) are compared in isolated ejecting
      rat, guinea pig, and ferret hearts. Intraventricular pressure fall data are taken
      from an isovolumic standard interval and from a subinterval of the latter,
      determined data-dependently by a statistical procedure. Extending the three
      parametric exponential fitting function to four-parametric models reduces
      regression errors by about 20-30%. No remarkable advantage of a particular four
      parametric model over the other was revealed. Enhanced relaxation, induced by
      isoprenaline, is more sensitively indicated by the asymptotic logistic time
      constant than by the usual exponential. If early and late parts of the isovolumic
      pressure fall are discarded by selecting a subinterval of the isovolumic phase,
      tau remains fairly constant in that central pressure fall region. Physiological
      considerations point to the logistic model as an advantageous method to cover
      lusitropic changes by an early and a late tau. Alternatively, identifying a
      central isovolumic relaxation interval facilitates the calculation of a single
      ("central") tau; there is no statistical justification in this case to extend the
      three-parametric exponential further to reduce regression errors.

PMID- 12071285
TI  - Rare variant of apolipoprotein E (Arg136-->Cys) in a subject with normal lipid
      values.
AB  - During the screening of apolipoprotein (apo) E gene polymorphism with PCR and
      subsequent restriction analysis, we have identified a female carrier with a
      mutant allele Arg136-->Cys. This proband had normal lipid parameters and no
      history of coronary artery disease (CAD). We did not confirm the previously
      described connection between apo E Arg136-->Cys mutation and elevated lipid
      levels. In the case of this mutation, other factors (environmental and/or
      genetic) are important for the development of lipid metabolism disorders.

PMID- 12071286
TI  - Mismatch of local blood flow and oxidative metabolism in stunned myocardium.
AB  - Myocardial blood flow is spatially heterogeneous, reflecting nonuniform oxygen
      supply. Also, myocardial oxidative metabolism is spatially heterogeneous. The
      effects of acute ischemia and reperfusion on the relationship between local
      myocardial blood flow (LMF) and oxidative metabolism are still unknown. LMF was
      measured in isolated, blood-perfused rabbit hearts using colored microspheres and
      oxidation water labeled with 18O2 (H2(18)O). Three protocols were performed: 18O2
      perfusion during normoxia (N; n=7), during early reperfusion (ER; 10 min, n=6),
      and late reperfusion (LR; 40 min, n=6) following 20 min no-flow ischemia. LMF and
      local H2(18)O residues were determined within defined myocardial samples (105+/
      15 mg). For interindividual comparison, values were normalized to the mean of the
      individual experiment and expressed as percentages. LMF ranged from 18 to 193%
      (N), 12 to 250% (ER), and 11 to 180% (LR). The H2(18)O tissue residue ranged from
      63 to 132% (N), 73 to 142% (ER) and 32 to 148% (LR). The correlation between LMF
      and local oxidative metabolism during N (r=0.77; n=56) was lost in the
      postischemic heart during ER and LR. LMF during N and ER were only weakly
      correlated (r=0.24; n=48), whereas LMF during N and LR correlated well (r=0.87;
      n=48). It is concluded that the heterogeneous LMF pattern at baseline is
      maintained in the stunned myocardium whereas that of local oxidative metabolism
      is not. Apart from the established mechanisms underlying myocardial stunning, a
      mismatch between local flow and oxidative metabolism might also contribute.

PMID- 12071287
TI  - Captopril fails to reverse hypertrophy of the left ventricle induced by aortic
      insufficiency in rabbits.
AB  - Angiotensin converting enzyme (ACE) inhibition has been reported to induce
      regression of hypertrophy in several models of hemodynamic pressure overload. The
      aim of the present study was to determine whether the ACE inhibitor captopril can
      reduce hypertrophy of the left ventricle induced by a chronic volume overload and
      modify collagen composition of the hypertrophied myocardium. Rabbits with four
      months lasting aortic insufficiency were divided into two groups: treated with
      captopril (20 mg/kg/day) for five weeks and treated with placebo. The respective
      control groups were represented by sham-operated animals. Aortic insufficiency
      induced a decrease of diastolic pressure, an increase of systolic and pulse
      pressure, hypertrophy of the left and right ventricle, and an increase of
      hydroxyproline content in the left ventricle without a change of hydroxyproline
      concentrations in either ventricle. Captopril treatment further enhanced pulse
      pressure by decreasing diastolic blood pressure. Hypertrophy of the left
      ventricle, hydroxyproline content and concentration in both ventricles were
      unaffected by captopril treatment. It is concluded that ACE inhibition did not
      reverse the left ventricular hypertrophy developed as a result of overload
      induced by aortic insufficiency. We suggest that mechanisms different from
      activation of the renin-angiotensin system may play a decisive role in the
      maintenance of hypertrophy in this particular model of volume hemodynamic
      overload.

PMID- 12071288
TI  - Myofibrillar creatine kinase activity inferred from a 3D model.
AB  - Myofibrillar creatine kinase (CK) that buffers ATP during fluctuating muscle
      energy metabolism has been selected for studies of conformational changes
      underlying the cellular control of enzyme activity. The force field was computed
      for three energetic states, namely for the substrate-free CK molecule, for the
      molecule conjugated with the MgATP complex, and for the molecule conjugated with
      the pair of reactants MgATP-creatine. Without its substrates, the enzyme molecule
      assumes an inactive "open" form. Upon binding of the MgATP complex, the CK
      molecule takes up a reactive "closed" conformation. Subsequent binding of
      creatine yields a nonreactive "intermediary" conformation. Acid-base catalysis is
      considered to be the basic principle for the reversible transfer of the
      phosphoryl group between the substrates. The results indicate that the substrate
      induced energy minimizing conformational changes do not represent a sufficient
      condition for CK activity and that some other essential component of
      physiological control at the cellular level is involved in the transition from
      the intermediary to the closed structure of the molecule.

PMID- 12071289
TI  - Transepithelial potential in mesonephric nephrons of 7-day-old chick embryos in
      relation to the histochemically detected sodium pump.
AB  - In order to obtain basic information on the transport properties of
      differentiating embryonic nephrons, we examined the 7-day-old chick mesonephros
      by measuring the transtubular epithelial potential difference (TPD) and by
      histochemical detection of Na,K-ATPase activity. TPD as an indicator of the
      electrogenic transport was measured in individual segments of superficial
      nephrons in vivo. Their electric polarity was always lumen-negative. TPD was
      reduced by addition of 10 mM KCN applied to the mesonephric nephrons from the
      outside. In the proximal tubules, TPD was significantly lower (mean+/-SD: -1.0+/
      0.5 mV) than in the distal and collecting tubules (-2.2+/-1.0 mV, p< or =0.05).
      Activity of the sodium pump was evaluated histochemically by detection of ouabain
      sensitive potassium-dependent p-nitrophenyl phosphatase in cryostat sections of
      the mesonephros. The enzyme activity was demonstrated only in distal tubules and
      in the collecting ducts, but not in the proximal tubules. These findings have
      revealed significant differences between embryonic nephron segments: the distal
      tubule, in contrast to the proximal one, is supplied by the sodium pump and is
      able to generate higher TPD. Therefore, we consider that it is only the distal
      nephron, which possesses the ability of active transport.

PMID- 12071290
TI  - Multinuclear NMR studies of an actively dividing artificial tumor.
AB  - Growth of the A549 cell line in a perfusion system suitable for use in a magnetic
      resonance study has been characterized and shown to be stable physiologically and
      hence appropriate for serial observations. Several methods of monitoring cell
      growth were compared to assess the behavior of the cells in this system.
      Comparison between NMR metabolite data and cell growth via cell counting showed
      that 31P NMR signals accurately reported cell doubling time. In contrast to most
      NMR cell culture systems, viable cells can be recovered from the perfusion system
      after the NMR measurements for further biochemical studies. These data further
      suggest that this system will be useful for studying the physiology and
      biochemistry of exponentially growing cells for at least two days in NMR tube
      culture.

PMID- 12071291
TI  - Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor
      patients.
AB  - The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in
      intron 6 (p53 MspI) have been suggested to be associated with the genetically
      determined susceptibility in diverse types of human cancer. In our hospital-based
      case-control study, we examined the allele and genotype incidence of these
      polymorphisms as well as their haplotype combinations in 60 brain tumor patients
      (27 males and 33 females) and 183 controls without malignancies. The genotype
      characteristics were determined by the PCR-based RFLP method using DNA extracted
      from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI
      polymorphisms are not associated with increased risk of brain tumors. Thus, we
      conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor
      suppressor gene p53 do not represent genetic determinants of susceptibility to
      brain tumors.

PMID- 12071292
TI  - Model of visually evoked cortical potentials.
AB  - The pattern-reversal (P-VEPs) and the motion-onset (M-VEPs) of visual evoked
      potentials were modeled by means of three damped oscillators (O1, O2, O3) of
      identical construction. The O1, assumed to simulate the response of primary
      visual area (V1), was driven by the firing density of the lateral geniculate
      nuclei. 01 contributed mainly to the N75 and P100 peaks of the P-VEPs. The O2,
      driven by the O1 output, mimics the activity of V2, V3a, and MT. It contributed
      to the negative peak N145 of the P-VEPs or to the N160 in the M-VEPs. The O3 was
      suggested to model late slow processes probably of an attentive origin. The model
      parameters were set by optimization to follow the P-VEPs and M-VEPs obtained as a
      grand average of four young volunteers (Pz - A2 lead). The evoked potentials were
      described with normalized root mean square error lower than 13%.

PMID- 12071293
TI  - Functional cross-talk of Ca2+-mobilizing endothelin receptors in C6 glioma cells.
AB  - There are conflicting results concerning the receptor subtype(s) involved in
      calcium-mediated endothelin signaling in the glial cells. In order to elucidate
      the role of endothelin A and B receptors in these processes, we have studied the
      effect of a complex spectrum of endothelin receptor ligands on intracellular
      calcium concentration changes in proliferating and differentiated C6 rat glioma
      cells. Cell differentiation was induced by dibutyryl-cAMP and assessed by the
      glial fibrillar acidic protein content. Intracellular calcium changes were
      measured in cell suspensions using fluorescent probe Fura-2. The specific
      endothelin B receptor agonists sarafotoxin S6c and IRL-1620 did not influence the
      intracellular calcium concentration. However, calcium changes induced by
      endothelin-1 and especially by endothelin-3 after the pretreatment of cells with
      one of these endothelin B receptor specific agonists were significantly enhanced
      even above the values attained by the highest effective endothelin concentrations
      alone. Such endothelin B-receptor ligand-induced sensitization of calcium
      signaling was not observed in differentiated C6 cells. Moreover, endothelin
      induced calcium oscillations in differentiated C6 cells were less inhibited by BQ
      123 and BQ-788 than in their proliferating counterparts. In conclusion, the
      specific activation of endothelin B receptor in C6 rat glioma cells does not
      affect intracellular calcium per se, but probably does so through interaction
      with the endothelin A receptor. The pattern and/or functional parameters of
      endothelin receptors in C6 rat glioma cells are modified by cell differentiation.

PMID- 12071294
TI  - Influence of photoperiod on the behavioral response to olfactory stimulation in
      the snail Helix pomatia L.
AB  - An ethanol vapor concentration of 1.6 mmol/l was used to test the diurnal
      variations of the olfactory response in two groups of snails, which were adapted
      to different light-dark cycles. The results revealed that the olfactory
      sensitivity to stimulation with ethanol was significantly increased during the
      day-time, which corresponds to the scotophase of the light-dark cycle, to which
      the animals had been adapted (chi2-test, P < 0.01).

PMID- 12071295
TI  - Association of obesity, diabetes, serum lipids and blood pressure regulates
      insulin action.
AB  - Insulin resistance is present in patients with Type 2 diabetes mellitus as well
      as in obese patients without diabetes. The aim of our study was to compare
      insulin action in diabetic and control persons with or without obesity and to
      evaluate the influence of serum cholesterol, serum triglyceride and blood
      pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic
      patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg x
      m(-2), and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique
      was performed at an insulin infusion rate of 1 mU x kg(-1) x min(-1) during 120
      min. We evaluated the metabolic clearance rate of glucose (MCR(G), ml x kg(-1) x
      min(-1)) as the most important indicator of insulin action by isoglycemic clamp.
      The Pearson's correlation and multiple regression models were used to compare
      studied factors with the insulin action. We found following predictors of insulin
      resistance expressed in the relationship with MCR(G): BMI (r = -0.68, p<0.001),
      plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55,
      p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38,
      p<0.01). From the multiple regression analysis we conclude that obesity may have
      even greater influence on the insulin action than diabetes mellitus itself.

PMID- 12071296
TI  - Unexpected inverse relationship between insulin resistance and serum homocysteine
      in healthy subjects.
AB  - Mild hyperhomocysteinemia has been established as a new independent risk factor
      for atherosclerosis and thrombosis. The metabolic syndrome of insulin resistance
      is associated with a high risk of coronary heart disease. Our objective was to
      determine if any relationship exists between the metabolic syndrome of insulin
      resistance in non-diabetic subjects and total serum homocysteine levels. Sixty
      six healthy volunteers (33 males and 33 females) were selected from the
      population of Pilsen. Insulin resistance was measured by the Insulin Suppression
      Test using Octreotide. Steady-state plasma glucose concentrations at the end of
      the test period provided a quantitative measure of insulin resistance. Serum
      homocysteine level was estimated by high-pressure liquid chromatography. Serum
      folate and vitamin B12 were estimated using commercial kits on an Abbott IMx
      analyzer. All other laboratory tests were performed by standard methods in a
      routine biochemical laboratory. Subjects with the highest tertile of steady-state
      plasma glucose showed a significantly higher body mass index, blood pressure,
      fasting plasma triglyceride levels, plasminogen activator inhibitor-1 and lower
      HDL-cholesterol, i.e. an insulin resistance pattern. These subjects had
      significantly lower serum homocysteine levels compared with non-insulin resistant
      subjects. The negative association of insulin resistance and serum homocysteine
      was unexpected. The contribution of plasma folate levels to serum homocysteine
      levels and serum creatinine was significantly negative and positive,
      respectively.

PMID- 12071297
TI  - The effect of an acute fat load on endothelial function after different dietary
      regimens in young healthy volunteers.
AB  - Attention has recently been focused on endothelial function after a single high
      fat meal, i.e. on the anticipated direct atherogenic effect of triglyceride-rich
      lipoproteins. Our study was designed to investigate the effect of a low-fat diet
      given for four weeks followed by a high-fat diet for another four weeks. At the
      end of each dietary period, a noninvasive ultrasound investigation of endothelial
      function of the brachial artery was performed along with laboratory tests.
      Endothelial function was measured immediately before the dietary load and after
      three and six hours in 11 healthy volunteers. The results were expressed as
      percentage of the changes in artery diameter at rest and during hyperemia; the
      data were processed using computer technology. When compared to the low-fat
      regimen, the total cholesterol content rose after the high-fat diet from 4.28
      mmol/l to 5.15 mmol/l (p<0.05) in the whole group of volunteers. There was no
      difference between both dietary regimens in baseline triglycerides. The brachial
      artery dilatation under basal conditions was 5.26+/-2.88 mm after the high-fat
      diet compared with the value of 3.13+/-3.01 mm (p<0.05) after the low-fat diet.
      When measured individually endothelial function in the whole group of volunteers
      in the course of the day, the degree of arterial dilatation after one month on
      low-fat diet was 3.13+/-3.0%, 3.88+/-2.5% and 5.23+/-3.3% at single measurement.
      When comparing arterial dilatation at two closest measurements, a non-significant
      trend, p>0.05 was seen in either case. The following values were obtained after
      one month on the high-fat diet: 5.26+/-2.9%, 4.47+/-1.7%, and 6.2+/-3.6%; again
      showing a non-significant trend of p>0.05. In this study, a single high-fat meal
      at the different dietary regimen did not significantly influence the
      vasoreactivity of the brachial artery in young volunteers.

PMID- 12071298
TI  - The application of biotechnology to nutrition: an overview.
AB  - Crop biotechnology is being used in two major ways to enhance human nutrition: to
      improve global food security by making more food available, especially locally
      grown and familiar foods in the developing world, and by enhancing the
      nutritional composition of foods that would interest both the developed and
      developing worlds. Since the first commercialized products of biotechnology are
      major commodity crops grown primarily in the US, Canada and Argentina (soybeans,
      corn, canola and cotton), there is concern about whether and when crop
      biotechnology will help the developing world. There are, however, several on
      going projects in Africa, SE Asia and Latin America where crop biotechnology is
      being used to enhance locally grown crops. The expectation is that genetically
      improved crops, e.g., those able to resist local pests, will allow even small
      scale farmers to grow more crops using fewer inputs and in an environmentally
      sustainable manner. Furthermore, there are numerous on-going projects to enhance
      the nutritional or health value of foods via transgene technology. A few of these
      projects are described in this article.

PMID- 12071299
TI  - The evolution of modern agriculture and its future with biotechnology.
AB  - Since the dawn of agriculture, humans have been manipulating crops to enhance
      their quality and yield. Via conventional breeding, seed producers have developed
      the modern corn hybrids and wheat commonly grown today. Newer techniques, such as
      radiation breeding, enhanced the seed producers' ability to develop new traits in
      crops. Then in the 1980's-1990's, scientists began applying genetic engineering
      techniques to improve crop quality and yield. In contrast to earlier breeding
      methods, these techniques raised questions about their safety to consumers and
      the environment. This paper provides an overview of the kinds of genetically
      modified crops developed and marketed to date and the value they provide farmers
      and consumers. The safety assessment process required for these crops is
      contrasted with the lack of a formal process required for traditionally bred
      crops. While European consumers have expressed concern about foods and animal
      feeds containing ingredients from genetically modified crops, Americans have
      largely been unconcerned or unaware of the presence of genetically modified foods
      on the market. This difference in attitude is reflected in Europe's decision to
      label foods containing genetically modified ingredients while no such labeling is
      required in the U.S. In the future, genetic modification will produce a variety
      of new products with enhanced nutritional or quality attributes.

PMID- 12071300
TI  - Food safety evaluation of crops produced through biotechnology.
AB  - Agricultural biotechnology has been widely adopted in agriculture but is also the
      focus of controversy. Questions have arisen regarding food and environmental
      safety. In the US, responsibility for ensuring agricultural and environmental
      safety is delegated to the USDA and EPA, respectively. The FDA has primary
      responsibility for food safety, with the exception that the EPA has
      responsibility for the safety of proteins in plants associated with insect
      defense mechanisms. The food safety assessment, whether performed by the FDA or
      the EPA, requires evaluation of the safety of 1) the newly added DNA, 2) the
      safety of the newly introduced gene product and 3) the overall safety of the
      balance of the food. A paradigm called "Substantial Equivalence" guides the
      assessment. The principal food safety issues for new varieties crops are 1)
      potential toxicity of the newly introduced protein(s), 2) potential changes in
      allergenicity, 3) changes in nutrient composition, 4) unintended effects giving
      rise to allergenicity or toxicity and 5) the safety of antibiotic resistance
      marker-encoded proteins included with the transgene. All of these must be taken
      in the context of the predicted range of dietary exposures. The evaluation seeks
      to establish that there is a "reasonable likelihood of safety" and that new
      varieties are as safe as or safer than crops produced by traditional methods.
      Indeed, after extensive safety testing and some five years of experience with
      such crops in the marketplace, there is not a single report that would lead an
      expert food scientist to question the safety of such transgenic crops now in use.

PMID- 12071301
TI  - The impact of consumer food biotechnology training on knowledge and attitude.
AB  - OBJECTIVE: Consumer education is an important aspect in the adoption of any new
      technology. The objective of this work was to determine whether consumer's
      knowledge and attitudes would be influenced by a face-to-face presentation
      involving food biotechnology. MATERIALS AND METHODS: Participants (576) were
      requested to complete a pre-test prior to receiving a 45-80 minute presentation,
      which was then followed by a post-test. Participants included members from a
      community organization, undergraduate and graduate college students and
      cooperative extension educators (county agents). RESULTS: Following training, 98%
      to 99% correctly indicated that fruits and vegetables contain chromosomes and
      that foods from biotech crops were currently sold in grocery stores. Prior to
      training, only 31% felt that these crops were properly regulated by federal
      agencies, and only 25% were confident that bioengineering was unlikely to make an
      existing food allergenic. Following training, 83% felt that these crops were
      properly regulated, and 63% believed that biotechnology was unlikely to add new
      allergens to our food supply. In addition, 90% of those trained would eat or
      serve genetically-modified foods to their family, and 90% believed that they or
      their family would benefit from genetically-modified foods within the next five
      years. CONCLUSIONS: It is apparent from these results that when provided sound,
      science-based information, participants are more accepting of this technology and
      the regulatory process.

PMID- 12071302
TI  - Enhancing mineral content in plant food products.
AB  - Plant foods can serve as dietary sources of all essential minerals required by
      humans. Unfortunately, mineral concentrations are low in some plants, especially
      many staple food crops; thus, efforts are underway to increase the mineral
      content of these foods as a means to ensure adequate attainment of dietary
      minerals in all individuals. While these efforts have included classical breeding
      approaches in the past, it is clear that future progress can be made by utilizing
      the tools of biotechnology to effect directed changes in plant mineral status.
      Reviewed are the short- and long-distance mineral transport mechanisms
      responsible for the root acquisition and whole-plant partitioning of mineral ions
      in crop plants. This background is used to discuss different transgenic
      strategies with the potential to enhance mineral content in vegetative and/or
      reproductive tissues. Due to various constraints imposed by plant transport
      systems on whole-plant mineral movement, it is argued that modifications designed
      to increase the supply of minerals to edible organs should have the highest
      chance for success. Examples of previous efforts to manipulate plant mineral
      nutrition through the introduction of novel transgenes are presented to
      demonstrate the utility of these approaches.

PMID- 12071303
TI  - Fighting iron deficiency anemia with iron-rich rice.
AB  - OBJECTIVE: Iron deficiency is estimated to affect about 30% of the world
      population. Iron supplementation in the form of tablets and food fortification
      has not been successful in developing countries, and iron deficiency is still the
      most important deficiency related to malnutrition. Here we present experiments
      that aim to increase the iron content in rice endosperm and to improve its
      absorption in the human intestine by means of genetic engineering. METHODS: We
      first introduced a ferritin gene from Phaseolus vulgaris into rice grains,
      increasing their iron content up to twofold. To increase iron bioavailability, we
      introduced a thermo-tolerant phytase from Aspergillus fumigatus into the rice
      endosperm. In addition, as cysteine peptides are considered major enhancers of
      iron absorption, we over-expressed the endogenous cysteine-rich metallothionein
      like protein. RESULTS: The content of cysteine residues increased about sevenfold
      and the phytase level in the grains about one hundred and thirtyfold, giving a
      phytase activity sufficient to completely degrade phytic acid in a simulated
      digestion experiment. CONCLUSIONS: This rice, with higher iron content, rich in
      phytase and cysteine-peptide has a great potential to substantially improve iron
      nutrition in those populations where iron deficiency is so widely spread.

PMID- 12071304
TI  - Enhancement of vitamin E levels in corn.
AB  - Vitamin E is the common name that describes eight naturally occurring compounds
      possessing alpha-tocopherol activity. These eight vitamin E compounds are
      collectively termed tocols, and all have antioxidant activity. There is natural
      variation among different corn breeding lines for levels of tocols. The two
      predominant isomers present in corn grain are gamma-tocopherol and alpha
      tocopherol. Alpha-tocopherol is considered more desirable for human and animal
      consumption because it has higher biological activity than gamma-tocopherol. Most
      corn breeding lines naturally have much more gamma-tocopherol than alpha
      tocopherol. Therefore a breeding goal is to increase levels of alpha-tocopherol
      relative to gamma-tocopherol. However, recent research suggests that gamma
      tocopherol and compounds metabolized from it have properties important to human
      health that are unique from properties of alpha-tocopherol. Therefore it may be
      desirable to not only increase levels of alpha-tocopherol in corn grain, but also
      levels of gamma-tocopherol. Determination of levels of tocopherols in corn grain
      is very laborious, requires HPLC analysis and is too time consuming for use in
      routine commercial corn breeding programs. Therefore we are performing
      biotechnology enabled molecular marker mapping of chromosomal regions with genes
      that control levels and ratios of alpha- and gamma-tocopherol. Breeders can use
      molecular markers we have identified to expediently select for desirable alleles
      of genes that will improve levels of alpha- and gamma-tocopherol in corn grain,
      without having to perform laborious HPLC assays. Another biotechnology strategy
      we have initiated is genetic transformation of corn with the gamma-tocopherol
      methyl transferase gene to enhance conversion of gamma-tocopherol to alpha
      tocopherol and thus increase levels of alpha-tocopherol. This transgenic strategy
      has been demonstrated in the model plant Arabidopsis, and we are now applying
      this approach to corn.

PMID- 12071305
TI  - Increased production of nutriments by genetically engineered crops.
AB  - Plants are the basis of human nutrition and have been selected and improved to
      assure this purpose. Nowadays, new technologies such as genetic engineering and
      genomics approaches allow further improvement of plants. We describe here three
      examples for which these techniques have been employed. We introduced the first
      enzyme involved in fructan synthesis, the sucrose sucrose fructosyltransferase
      (isolated from Jerusalem artichoke), into sugar beet. The transgenic sugar beet
      showed a dramatic change in the nature of the accumulated sugar, 90% of the
      sucrose being converted into fructan. The use of transgenic sugar beet for the
      production and isolation of fructans will result in a more efficient plant
      production system of fructans and should promote their use in human food. The
      second example shows how the over-expression of the key enzyme of flavonoid
      biosynthesis could increase anti-oxidant levels in tomato. Introduction of a
      highly expressed chalcone isomerase led to a seventyfold increase of the amount
      of quercetin glucoside, which is a strong anti-oxidant in tomato. We were also
      able to modify the essential amino acid content of potato in order to increase
      its nutritional value. The introduction of a feedback insensitive bacterial gene
      involved in biosynthesis of aspartate family amino acids led to a sixfold
      increase of the lysine content. Because the use of a bacterial gene could appear
      to be controversial, we also introduced a mutated form of the plant key enzyme of
      lysine biosynthesis (dihydrodipicolinate synthase) in potato. This modification
      led to a 15 times increase of the lysine content of potato. This increase of the
      essential amino acid lysine influences the nutritional value of potato, which
      normally has low levels of several essential amino acids. These three examples
      show how the metabolism of primary constituents of the plant cell such as sugar
      or amino acids, but also of secondary metabolites such as flavonoids, can be
      modified by genetic engineering. Producing fructan, a soluble fiber, increasing
      the level of flavonoids, an antioxidant, in tomato or increasing the level of
      essential amino acids in potato are all clear examples of plant genetic
      modifications with possible positive effects on human nutrition.

PMID- 12071306
TI  - High-oleic and high-stearic cottonseed oils: nutritionally improved cooking oils
      developed using gene silencing.
AB  - Gene technology and plant breeding are combining to provide powerful means for
      modifying the composition of oilseeds to improve their nutritional value and
      provide the functional properties required for various food oil applications.
      Major alterations in the proportions of individual fatty acids have been achieved
      in a range of oilseeds using conventional selection, induced mutation and, more
      recently, post-transcriptional gene silencing (PTGS). In particular, a number of
      high-oleic oils have been developed in order to provide high-stability cooking
      oils. These oils provide the opportunity to replace the current widespread use of
      saturated fats and hydrogenated oils that contribute significantly to increased
      risk of cardiovascular disease due to the effect of saturated and trans-fatty
      acids on elevating LDL cholesterol in the bloodstream. Similarly, oils with
      increased stearic acid content are being developed to enable the production of
      solid fats without the need for hydrogenation. We have recently applied hpRNA
      mediated PTGS in cotton to down-regulate key fatty acid desaturase genes and
      develop nutritionally-improved high-oleic (HO) and high-stearic (HS) cottonseed
      oils (CSOs). Silencing of the ghFAD2-1 delta12-desaturase gene raised oleic acid
      content from 13% to 78% and silencing of the ghSAD-1 delta9-desaturase gene
      substantially increased stearic acid from the normal level of 2% to as high as
      40%. Additionally, palmitic acid was significantly lowered from 26% to 15% in
      both HO and HS lines. Intercrossing the HS and HO lines resulted in a wide range
      of unique intermediate combinations of palmitic, stearic, oleic and linoleic
      contents. The oxidative stability, flavor characteristics and physical properties
      of these novel CSOs are currently being evaluated by food technologists.

PMID- 12071308
TI  - Expression of human milk proteins in plants.
AB  - Human milk proteins are believed to have a multitude of biological activities
      benefiting the newborn infant. Such functions include antibacterial and antiviral
      activities, enhancement of the immune system and increased nutrient absorption.
      To date, only breast-fed infants have been exposed to these proteins. However, by
      using genetic engineering it is now possible to express these proteins in plants,
      such as rice, at very high levels. Recombinant human milk proteins can
      subsequently be added to infant formula and baby foods. Prior to such addition,
      safety tests and efficacy trials need to be conducted. The safety tests will
      initially be done in rats and then in humans. The efficacy trials should also
      evaluate stability against heat treatment (processing), pH (stomach conditions)
      and proteolytic enzymes (digestion). To date, we have expressed recombinant human
      lactoferrin, lysozyme and alpha1-antitrypsin in rice at very high expression
      levels. These recombinant proteins showed a stability and activities similar to
      those of the native milk proteins, suggesting that they may be able to exert
      biological activities in infants when added to formula or baby foods.

PMID- 12071307
TI  - Foods as production and delivery vehicles for human vaccines.
AB  - Vaccination is a great asset for eradication of infectious diseases in humans and
      animals. With the prevalence of antibiotic resistant bacterial strains and an
      alarming increase in new and re-emerging pathogens, the need for vaccination
      continues to be a high priority for mammalian diseases. In the last several
      years, a novel approach for developing improved mucosal subunit vaccines has
      emerged by exploiting the use of genetically modified plants. It has been
      demonstrated that plant-derived antigens are functionally similar to conventional
      vaccines and can induce neutralizing antibodies in mammalian hosts. Using
      genetically engineered plants for the production of immunogenic peptides also
      provides a new approach for the delivery of a plant-based subunit vaccine, i.e.,
      oral delivery, provided these immunogenic peptides are expressed in an edible
      part of the plant, such as grain or fruit. Thus, food crops can play a
      significant new role in promoting human health by serving as vehicles for both
      production and delivery of vaccines.

PMID- 12071309
TI  - Association of periphytic diatom species of artificial substrate in lotic
      environments in the Arroio Sampaio Basin, RS, Brazil: relationships with abiotic
      variables.
AB  - Associations of diatom species were identified, in the Arroio Sampaio Basin, Rio
      Grande do Sul, Brazil, based on monthly samplings over a year along Arroio
      Sampaio and its main tributaries, using polyamide thread as an artificial
      substrate. The species groupings showed four different environments: medium-lower
      course of Arroio Sampaio; and lower course of Arroio Teresinha; upper course of
      Arroio Sampaio; and lower course of Arroio Duvidosa. Among the physical and
      chemical variables measured, water pollution, particularly organic contamination
      and eutrophication, measured from BOD, and total phosphate concentration,
      respectively, appeared to be one of the most important environmental factors
      determining the composition and structure of species associations in the area
      studied.

PMID- 12071310
TI  - Temporal and spatial patterns on serra, Scomberomorus brasiliensis (Teleostei,
      Scombridae), catches from the fisheries on the Maranhao coast, Brazil.
AB  - The displacement pattern of the serra, Scomberomorus brasiliensis, in North
      eastern Brazil was analyzed from landing data recorded form the fleet fishing
      serra. Serra fishery has two seasons: from Septemer to February (demersal species
      plus serra), and from March to August (almost only large amounts of serra). S.
      brasilienisis relative abundance increases similarly along the coast from March.
      but decreases first on the West coast from June. Records indicate that serra is
      near the coast at least until September/October in Eastern grounds. From October
      to March (strongest spawning season) there is no record of shoals on the coast.
      We concluded that the Maranhao coast is just a part of the migration circuit of
      S. brasilienisis that may exceed 300 nautical miles.

PMID- 12071311
TI  - The effect of hypoxia and recuperation on carbohydrate metabolism in pacu
      (Piaractus mesopotamicus).
AB  - A study of the hematological parameters, glycogen, glucose, and lactate, and the
      activity of malate and lactate dehydrogenases was carried out in blood and
      tissues of fishes submitted to two, four, and six hours of hypoxia and
      recuperation. Only after 4 h of hypoxia was there a drop in liver glucose. Alter
      16 h, a drop in lactate and a rise in glucose in practically all tissues signaled
      a recuperation of the metabolism, probably due to ASR (aerial surface
      respiration). Lactate formed during hypoxia was canalized to heart and brain for
      oxidation and used for neoglucogenesis. There were no changes in hematological
      parameters nore in the activity of malate and lactate dehydrogenases during
      normoxia and hypoxia, which suggest that these adaptive mechanisms may not be
      involved during hypoxia. Glycogen concentrations did not show variation during
      hypoxia either.

PMID- 12071312
TI  - Nutritional status response of daphnia laevis and Moina micrura from a tropical
      reservoir to different algal diets: Scenedesmus quadricauda and Ankistrodesmus
      gracilis.
AB  - The accumulation of lipid reserves was investigated in two common cladoceran
      species typical of neotropical freshwaters. Experiments were performed in order
      to measure differential accumulation of lipid reserves in response to two algal
      diets, S. quadricauda and A. gracilis. The larger D. laevis fed with the
      Ankistrodesmus diet accumulated a higher amount of total lipids. The average
      lipid content for both diets was 1.1% and 22.1% dry weight for Scenedesmus and
      Ankistrodemsus, respectively. This difference was found to be highly significant.
      The superior nutritional quality of A. gracilis was confirmed by the experiments
      using the smaller Moina micrura. This cladoceran accumulated 11.4% and 19.9% of
      the average dry weight of lipids from Scenedesmus and Ankistrodesmus,
      respectively. The study also found that most lipid reserves are concentrated as
      triacylglycerols in both cladocerans. The relative contribution of this class of
      lipids also varied according to the diet. For Daphnia, for instance, the average
      triacylglycerol levels varied from 6.2 to 11.0 with the Scenedesmus and
      Ankistrodesnus diets, respectively.

PMID- 12071313
TI  - Distribution of fish assemblages in Lajes reservoir, Rio de Janeiro, Brazil.
AB  - Spatial distribution of fish assemblages in Lajes Reservoir, a 30 km2 impoundment
      in Rio de Janeiro State (Lat. 22 degrees 42'-22 degrees 50'S; Long. 43 degrees
      53'-44 degrees 05'W) was assessed to detect patterns of available habitat use by
      the fish. A standardized monthly sampling program was carried out from January to
      December 1994 at three zones of the reservoir (upper, near tributary mouths;
      middle; and lower, near the dam). Fishes were caught by gillnets, (50 m long, 3 m
      height), with mesh ranging having from 25 to 45 mm between knots, submerged
      during 12 hours. A total of 5,089 fishes were collected comprising 15 species, 14
      genera and 9 families. Loricariichthys spixii, Astyanax bimaculatus,
      Parauchenipterus striatulus. Astyanax fasciatus parahybae, Oligosarchus hepsetus,
      Rhamdia parahybace, Hypostomus affinis. and Geophagus brasiliensis were the most
      abundant species, each contributing above 1% of the total number. Loricariichthys
      spixii was the dominant species, contributing over 80% of total number and
      biomass. Fish abundance, number of species, and biomass were higher in the upper
      zone, but differences from this overall pattern were shown by some species.
      Loricariichthys spixii and Rhamdia parahybae were more abundant in the upper
      zone, while all other species showed no differences in their abundance among the
      zones. Seasonal environmental variables of temperature, pH, transparency, and
      water level did not show a clear association with fish occurrence. Most fish used
      the different zones of the reservoir with no clear sign of spatial separation.
      High dominance of L. spixii. reduced abundance of reolific species Leporinus
      copelandii and Cyphocharax gilberti, and presence of introduced species such as
      Cichla monoculus and Tilapia rendallalli are indications of antropic effects in
      the fish community.

PMID- 12071314
TI  - Short-term variability of copepod abundance in Jurumirim Reservoir, Sao Paulo,
      Brazil.
AB  - Short-term variability in composition and abundance of copepod populations were
      studied during the dry (winter) and rainy (summer) seasons, at the dam region of
      Jurumirim Reservoir, Sao Paulo, Brazil. An intensive sampling program was carried
      out during 30 days in each period of the year. Samples and measurements were
      taken every other day at 0, 5, 10, 15, 20 and 25 m depths. The relationship
      between variability of the populations and some environmental factors was
      analyzed. The main species were: Argyrodiaptomus furcatus (Sars), Notodiaptomus
      iheringi (Wright), Mesocyclops longisetus (Thiebaud), Thermocyclops decipiens
      (Fischer), and T. minutus (Lowndes). Thermocyclops minutus was the most abundant
      species in dry season and its abundance varied significantly between sampling
      days. A large increase in abundance of calanoids occurred during the rainy
      season. This increase was correlated with higher temperature values. At that
      time, Notodiaptomus iheringi was dominant. This species showed significant short
      term variations in abundance in both dry and rainy seasons. Significant variation
      in density of populations within the same sampling period might result from
      either the dispersion pattern of the populations or continuous substitution of
      the water masses. Significant correlation was observed between copepod abundance
      and temperature, especially for species of calanoids and there was also some
      correlations between densities of particular species of copepods and some
      phytoplankton taxa, mainly during the dry season. As for vertical distribution,
      most organisms were found between the surface and 15 m deep. During the rainy
      season, there was some evidence of the occurrence of spatial segregation between
      species of cyclopoids and calanoids, with the cyclopoids in a deeper position
      within the water column.

PMID- 12071315
TI  - What is so special about mangroves?
AB  - The title question of this short paper has been addressed to me countless times
      by persons from all walks of life. The paper is a concise answer to the question;
      it might go halfway towards satisfying the questioners, but not more than
      halfway. This paper identifies the uniqueness of mangrove ecosystems in that they
      are created and sustained by a small number of rooted vascular plants in the
      intertidal area of the tropics. In addition to being a marginal ecosystem, a
      mangrove is unique in that, as an ecosystem it has various interactions with
      other ecosystems, both adjoining and remote in space and time. Another unique
      feature of mangroves is that, unlike most marginal ecosystems, they are highly
      productive and dynamic. Healthy mangrove ecosystems also have the peculiar
      ability to immobilize heavy metals.

PMID- 12071316
TI  - Soil temperature and diapause maintenance in eggs of the spittlebug, Deois
      flavopicta (Hemiptera: Cercopidae).
AB  - Diapausing eggs of the neotropical pasture pest, Deois flavopicta (Stal)
      (Hemiptera: Cercopidae), were exposed to low overnight temperatures that
      simulated field conditions during the dry season (23/12, 23/15 and 23/18 degrees
      C day/night), for different periods (0-60 days). After treatment, eggs were kept
      at 28 degrees C and contact water (100% humidity) until hatching. A group of
      diapausing eggs were kept all the time under this last condition as a control
      treatment. Time for hatching (in degree-days) was reduced with decrease in low
      overnight temperature and increase of exposure time to these cold shocks,
      although there was no interaction between the factors. Regression of exposure
      time to cold shock influencing the expected mean hatching time produced
      independent equations for temperatures below 18 degrees C and 15 degrees C. We
      constructed a model that simulates the expected proportion of the population
      hatching after the beginning of rainy season based on regression equations to
      mean hatching time and associated standard deviation. The simulation generated
      for the model correlated significantly with nymphal population observed in the
      field. These results showed that overnight soil temperatures below 18 degrees C,
      as occurs in Central and South-eastern Brazil between May and August, shorten the
      period of diapause, increase quiescent eggs in the soil, and may have synchronize
      population hatching.

PMID- 12071317
TI  - Astyanax fasciatus as bioindicator of water pollution of Rio dos Sinos, RS,
      Brazil.
AB  - The effects of an increasing downriver pollution gradient on the reproductive
      system of Astyanax fasciatus were investigated in the Rio dos Sinos, RS. The
      comparison of mean oocyte diameters, gonadal indices and gonado-somatic
      relationships of specimens captured in polluted areas with individuals from
      unpolluted reference sites revealed a significant decrease of these parameters
      with increasing water pollution. High loads of organic and industrial sewage are
      considered responsible for these effects. Condition factors showed an inverse
      relationship, and increased significantly in down-river polluted areas. The
      declining gonadal indices showed that energy was allocated to somatic growth. The
      results of the study recommend the use of A. fasciatus in biomonitoring essays.

PMID- 12071318
TI  - Population biology of Parides anchises nephalion (Papilionidae) in a coastal site
      in Southeast Brazil.
AB  - A population of Parides anchises nephalion was studied during seven months in SE
      Brazil. The population size was about 10-20 individuals (with theoretical maximum
      near 60 individuals), with small variations in some months. Sex ratio was male
      biased, with males dominating in all months. The age structure was not stable,
      with an increase in new individuals before the population peak in December. The
      residence time was 14.1 +/- 8.2 days for males and 9.0 +/- 3.6 for females, with
      maximum registered of 30 days. Males can travel distances of up to 400 m, but
      most individuals were always recaptured in the same site. The mean forewing
      length was greater in females. The population features agree with those found in
      other species of Parities in other neotropical sites.

PMID- 12071319
TI  - Community of male Euglossini bees (Hymenoptera: Apidae) in a secondary forest,
      Alcantara, MA, Brazil.
AB  - From September, 92 to August, 93 bee sampling was done in a secondary forest near
      the Pepital River, in Alcantara, MA, in order to study the local Euglossini
      fauna. Five aromatic compounds were used: eucaliptol, eugenol, methyl salicylate,
      vanillin, and benzoate. Four hundred sixty-seven male Euglossini bees were
      captured, distributed in 4 genus and 19 species. Euglossa was the most abundant
      and with high diversity (302 specimens and 14 species), followed by Eulaema (121;
      3), Eufriesea (41; 1), and Exaerete (3; 1). The species which more frequently
      visited the bait were Euglossa piliventris (141 specimens; 30.19%), Euglossa
      cingulata (113; 24.21%), Euglossa ignita (45; 9.64%), Eufrieseapulchra (41;
      8.78%), and Euglossa gaianii (33; 7.07%) corresponding to 79.88% of the sampling
      universe. The bees were active throughout the year, however during the rainy
      season more activity and diversity were observed. The most attractive essence was
      eucaliptol (44.32% specimens and 84.21% species). In spite of this study having
      been done in a forest fragment, a secondary vegetation area smaller than other
      areas studied in Maranhao, it showed a significant diversity rate. This result
      reinforces the importance of fragments in the conservation of local bee
      communities.

PMID- 12071320
TI  - Piscinoodinium pillulare (Schaperclaus, 1954) Lom, 1981 (Dinoflagellida)
      infection in cultivated freshwater fish from the northeast region of Sao Paulo
      State, Brazil. Parasitological and pathological aspects.
AB  - The Aquaculture Center of Unesp, Jaboticabal, SP, Brazil, received fishes for
      diagnosis from fish farmers reporting fish crowding at pond edges and in water
      inlets. Fifty-three out of 194 cases showed round to oval, immobile whitish
      structures, measuring up to 162 microm diameter, identified as the dinoflagellate
      Piscinoodinium pillulare. In 34 diagnosed cases the parasites were present in the
      gills, in 2 on body surface, and 9 in both. Thirty-one out of 53 were tambacu
      hybrids hosts; 7, Piaractus mesopotamicus; 6, Colossoma macropomum; 5, Leporinus
      macrocephalus; 3, Oreochromis niloticus; and 1, Prochilodus lineatus. Fish showed
      increased mucous production on body surface and gills, while ecchymosis in the
      caudal peduncle and operculum was present. The gills also showed paleness,
      congestion, and petechiae. Histopathology presented a great number of trophonts
      situated between secondary lamellae, fixed to or detached from the epithelium.
      Primary lamellae presented interstitial hemorrhages, severe hyperplasia of the
      epithelium, goblet cells, and mononuclear infiltrates. The present work is the
      first report of P pillulare in Brazil and emphasizes the importance of this
      dinoflagellate which caused significant economic losses from 1995 through 1997.

PMID- 12071321
TI  - African dung beetle Onthophagus gazella Fabricius (Coleoptera: Scarabaeidae)
      esterase isozymes.
AB  - African beetles Onthophagus gazella from both sexes were analyzed by
      electrophoresis for an investigation of esterase isozymes using alpha-naphthyl
      propionate and methylumbelliferyl propionate as substrates. Only one of the
      esterases (Est. 6) reacted with one of the substrates (alpha-naphthyl
      propionate). Six areas of activity were found, two of them being polymorphic
      (Est. 3 and Est. 4). For presence of Est. 3, 337 individuals were analyzed,
      including descendants of 32 controlled crossings: two alleles were identified,
      whose frequencies are Est. 3A = 0.447 and Est. 3B = 0.553. The population is in
      equilibrium for this locus (qui-square = 4.18; 0.2 > P > 0.1). For Est. 4, 338
      individuals, descendants of 32 controlled crossings, were analysed. In this case,
      three alleles were identified whose frequencies are: Est. 4A = 0.277; Est. 4B =
      0.661; and Est. 4C = 0.062. The population is not in equilibrium for this locus
      (qui-square = 40.259; p < 0.001). Two esterases were detected only in the pupal
      stage and another one in larvae. Of the 23 loci analyzed in these insects up to
      now, 3 are polymorphic (13%), which indicates very low variability in the
      population here studied.

PMID- 12071322
TI  - Diet of eared doves (Zenaida auriculata, Aves, Columbidae) in a sugar-cane colony
      in South-eastern Brazil.
AB  - Farmers in the Paranapanema Valley (Sao Paulo, Brazil) have reported problems
      with flocks of Eared Doves (Zenaida auriculata) eating sprouting soybeans. In
      this region these birds breed colonially in sugar-cane, and eat four crop seeds,
      using 70% of the dry weight, in the following order of importance: maize, wheat,
      rice, and soybeans. Three weeds (Euphorbia heterophylla, Brachiaria plantaginea,
      and Commelina benghalensis) were important. This information suggests that the
      doves adapted particularly well to the landscape created by the agricultural
      practices in the region, exploiting many available foods.

PMID- 12071323
TI  - Biology of Anicla infecta (Ochsenheimer, 1816) (Lepidoptera, Noctuidae,
      Noctuinae), under laboratory conditions.
AB  - Larvae of Anicla infecta (Ochsenheimer, 1816) (Noctuidae) feed upon many grasses
      and may be harmful to cereals and fodder of economic importance. This study was
      developed aiming to contribute to knowledge of the biology of this species. The
      rearing was done in an environmental chamber with the following settings:
      temperature of 25 +/- 1 degrees C; relative humidity of 70% +/- 10%, and
      photoperiod of L14:D10. The larvae fed on ryegrass, Lolium multiflorum Lam. The
      results express the mean and standard error for the length of every stage in
      days. For each stage we observed the following time of development: egg 3.2 +/-
      0.09; larvae 18.7 +/- 0.07; pre-pupae 3.3 +/- 0.04; pupae 12.6 +/- 0.14; and
      adult longevity was 12.1 +/- 1.03. Also the pre-egg-laying period was 4.4 +/-
      0.59; the egg-laying period was 8.1 +/- 0.84; and the post-egg-laying period was
      0.3 +/- 0.14. The mean number of egg-laying cycles per female was 6.7 +/- 0.73;
      that of eggs per cycle was 77.5 +/- 4.37; and total eggs per female was 521.4 +/-
      47.36.

PMID- 12071324
TI  - Genetic variability and social structure of Colonies in Acromyrmex heyeri and A.
      striatus (Hymenoptera: Formicidae).
AB  - The breeding structure of both colony and population of social insects can be
      examined by genetic analysis. Colonies of the leaf-cutting ants Acromyrmex heyeri
      and A. striatus (Myrmicinae, Attini) were thus analyzed for isoenzyme systems
      MDH, a-GPDH, and AMY to describe genotype variability and social structure. A
      total of five loci were investigated (three for amylase and one for each other
      system). Ninety-seven colonies of A. heyeri and 103 of A. striatus were sampled
      in different localities in Southern Brazil (State of Rio Grande do Sul). The
      genotypes found show the occurrence of monogyny and polygyny associated or not
      with polyandry, which indicates that the social organization is colony-specific.
      The polygyny and polyandry observed are likely to be responsible for the great
      genotypic diversity of the colonies. The average inbreeding coefficient per
      colony was higher in A. striatus than in A. heyeri, which may reflect the
      different patterns of production of sexual individuals and nuptial flight of
      those two species.

PMID- 12071325
TI  - The effect of treatment with melatonin upon the ultrastructure of the mouse
      pineal gland: a quantitative study.
AB  - In order to evaluate melatonin implication in the regulating of its own secretory
      process by pinealocytes, we used morphometric techniques for transmission
      electron microscopy. In mice treated with 100 mg of melatonin (N-acetyl-5-methoxy
      tryptamine) by daily subcutaneous injection, we observed a decrease in number and
      volumetric density of lysosomes. Our results showed that melatonin influences the
      secretory activity of pinealocytes and participates in a complex secretory
      regulating mechanism.

PMID- 12071326
TI  - Androlaelaps marmosops (Acari: Laelapidae), a new species associated with the
      mouse opossum, Marmosops incanus (Lund, 1840) in the Atlantic forest of Rio De
      Janeiro State, Brazil.
AB  - Androlaelaps marmosops, a new species of laelapid mite, is described from the
      pelage of the mouse opossum, Marmosops incanus (Lund, 1840) (Mammalia:
      Didelphidae), in two areas of Atlantic Forest of Rio de Janeiro State.
      Measurements and illustrations are included for females only.

PMID- 12071327
TI  - Notes on the coati, Nasua nasua (Carnivora: Procyonidae) in an Atlantic forest
      area.
AB  - Although Nasua nasua is broadly distributed geographically and relatively common,
      it is still little studied. This paper reports observations of coatis in an
      Atlantic Forest area, the Parque Estadual Carlos Botelho (PECB) in Sao Paulo
      State, Brazil. The social structure of coatis at PECB seems to be the same
      related in the literature. The mating season appears to be August-September and
      the pups are born in October-November. Coatis are mainly arboreal at the PECB,
      contrasting with habits reported in the data from other areas. This preference
      for the arboreal stratum no doubt is related to their foraging in epiphytic
      bromeliads, which occurred in 90.6% of the instances in which they were observed
      feeding. Bromeliads are a rich food source much more common in the Atlantic
      Forest than in other areas where coatis have been observed. This result suggests
      that this species is able to adjust its foraging and strata preferences to
      different environments without changing its basic social structure.

PMID- 12071328
TI  - Effect of arbuscular mycorrhizal fungi and soil phosphorus level on expression of
      protein and activity of peroxidase on passion fruit roots.
AB  - The effects of mycorrhizal inoculation and increasing soil P levels on the
      expression of total proteins and peroxidase activity on passion fruit roots were
      evaluated. The experimental design was entirely at random, with four treatments
      of inoculation (a--control; b--Gigaspora albida; c--Scutellospora heterogama; d-
      mixture of G. albida, G. margarita, S. heterogama, and Glomus clarum) x three
      levels of soil P (4, 11, and 30 mg/dm3 of soil), each with three replicates.
      Plants were harvested 70 days after inoculation, when root colonization, shoot P
      level, protein content, and enzymatic activity of peroxidase (PAGE--7%) on root
      extract were evaluated. Regarding protein, there was no significant difference
      among the treatments, except between those roots receiving mixed inoculum and 11
      mg P/dm3 of soil. Effect of P on protein concentration, when compared with the
      inoculation effect was observed. For peroxidase, there was an eletrophoretic band
      common to all treatments (rf: 0.43) and another that was absent only in
      noncolonized plants, grown in soil with lower P (rf: 0.46). Mycorrhizal specific
      bands were not present but a small decrease of intensity of bands in noncolonized
      plants was observed. Conversely, the control roots presented a single band (rf:
      0.33) not observed in the other extracts, that may demonstrate an inhibitory
      effect of AMF on some host activities. The data showed the influence of P level
      in soil on the protein expression of roots, suggesting the influence of this
      nutrient on root genetic expression as well as on the mechanisms of symbiotic
      control/recognition.

PMID- 12071329
TI  - First record of Alona setigera Brehm (Cladocera, Chydoridae) in the neotropical
      region.

PMID- 12071330
TI  - The occurrence of phoenicopterus chilensis Molina (Aves, Phoenicopteridae) in Sao
      Paulo State reservoirs.

PMID- 12071331
TI  - Enteric nerves and diarrhoea.
AB  - This review article discusses the importance of the enteric nervous system for
      the fluid and electrolyte secretion evoked by luminal secretagogues in the small
      intestine. The first part of the review summarizes observations on augmented
      secretion caused by cholera toxin, which has been the subject of extensive
      studies in the past. The latter part reviews studies of the participation of the
      enteric nervous system in other secretory states of the gut. The involvement of
      the enteric nervous system in the pathophysiology of intestinal secretory states
      opens up potential new sites of actions for drugs in the treatment of diarrhoea.
      This is discussed in the final part of this review.

PMID- 12071332
TI  - Effects of epomediol on ethinyloestradiol-induced changes in glutathione
      homeostasis in the rat.
AB  - Epomediol is a synthetic terpenoid compound that has been reported to reduce
      ethinyloestradiol-induced cholestasis. The choleretic action of epomediol is
      related to an increase in both the bile acid-dependent and independent fractions
      of bile flow, but the role of glutathione metabolism and transport is still
      unknown. This study was aimed to evaluate if changes in glutathione homeostasis
      could contribute to the beneficial effects of epomediol in rats with
      ethinyloestradiol-induced cholestasis. When compared to control animals,
      ethinyloestradiol treatment resulted in a significant decrease in the liver
      concentration of reduced (GSH) and oxidized glutathione. Both GSH and oxidized
      glutathione concentrations returned to normal in animals receiving
      ethinyloestradiol plus epomediol. Ethinyloestradiol administration induced a
      significant decrease in plasma and renal GSH and the tripeptide was almost absent
      from bile. Combined treatment with epomediol plus ethinyloestradiol normalised
      renal GSH and both biliary and liver cysteine were significantly increased. Liver
      and kidney gamma-glutamyltranspeptidase activities were higher in rats receiving
      ethinyloestradiol and still remained elevated in animals with the combined
      treatment. Liver gamma-glutamylcysteine synthetase activity rose significantly by
      administration of ethinyloestradiol plus epomediol but the corresponding mRNA
      levels were not modified. Changes in glutathione homeostasis and higher biliary
      levels of GSH amino acid constituents could contribute to the beneficial effects
      of epomediol in rats with ethinyloestradiol-induced cholestasis.

PMID- 12071333
TI  - In vitro metabolism of two heterocyclic amines, 2-amino-9H-pyrido[2,3-b]indole
      (A(alpha)C) and 2-amino-3-methyl-9H-pyridol2,3-b]indole (MeA(alpha)C) in human
      and rat hepatic microsomes.
AB  - 2-Amino-9H-pyrido[2,3-b]indole (A(alpha)C) and 2-amino-3-methyl-9H-pyrido[2,3
      b]indole (MeA(alpha)C) are two mutagenic and carcinogenic heterocyclic amines
      formed during ordinary cooking. In this study, we have investigated the in vitro
      metabolism of tritium-labelled A(alpha)C and MeA(alpha)C in hepatic microsomes
      from human pools, rats induced with polychlorinated biphenyl (PCB) (Aroclor 1254)
      and control rats. The microsomes were incubated with A(alpha)C and MeAaC and the
      detoxified and activated metabolites of A(alpha)C and MeA(alpha)C were separated
      and characterised by HPLC-MS. A(alpha)C is metabolised to two major and three
      minor detoxified metabolites, while MeA(alpha)C is metabolised to three major and
      one minor detoxified metabolites. Some A(alpha)C and MeA(alpha)C are activated by
      oxidation to the reactive metabolites N2-OH-A(alpha)C and N2-OH-MeA(alpha)C,
      respectively. These reactive N2-OH-metabolites react partially in the incubation
      system with formation of protein adducts, dimers and the parent compound by
      reduction of the N2-OH-metabolites. The distribution between the detoxified and
      activated metabolites in the different types of hepatic microsomes showed same
      pattern for both A(alpha)C and MeA(alpha)C. In PCB-induced rat microsomes, the
      major part of the metabolites are detoxified, only a little amount is activated.
      In control rat microsomes there is a fifty-fifty distribution between
      detoxification and activation, while the major part of the metabolites from the
      human microsomes are activated and reacts to form dimers and protein adducts.
      These data show that, in human hepatic microsomes compared to rat hepatic
      microsomes, a major part of A(alpha)C and MeA(alpha)C are metabolically activated
      to the reactive N2-OH-A(alpha)C and N2-OH-MeA(alpha)C.

PMID- 12071334
TI  - Altered pharmacokinetics and metabolism of valproate after replacement of
      conventional valproate with the slow-release formulation in epileptic patients.
AB  - Altered metabolism of valproate has been suggested as the mechanism of
      teratogenicity and hepatotoxicity of valproate. This study aimed at examining
      whether pharmacokinetics of a slow-release formulation of valproate affects
      valproate metabolism. Thirty-one epileptic patients were treated with fixed-doses
      of conventional valproate for at least 2 months. Thereafter, the drug was
      replaced with the same doses of slow-release formulation of valproate for 2
      months. Blood samplings for determination of valproate and its metabolites by gas
      chromatography-mass spectrometry were performed at three time-points (just before
      morning dose and at 1 and 5 hr after morning dose) during both treatment phases.
      There was a significant difference (P < 0.005) in the mean serum concentration
      (+/- S.D.) of valproate after 1 hr between conventional valproate (63.1 +/- 27.9
      microg/ml) and slow-release formulation of valproate (45.7 +/- 19.5 microg/ml).
      Mean serum concentrations (+/- S.D.) of 4-en and hydroxy metabolites after 5 hr
      were significantly reduced after replacement with slow-release formulation of
      valproate (4-en: 29.5 +/- 14.0-->23.0 +/- 15.3 ng/ml, 3-OH: 488.5 +/- 234.0-
      >419.6 +/- 171.1 ng/ml, 4-OH: 404.3 +/- 124.7-->342.8 +/- 147.6 ng/ml, 5-OH:
      102.8 +/- 54.4-->81.0 +/- 43.6 ng/ml). The present study suggests that smaller
      diurnal fluctuations in valproate concentrations during treatment with slow
      release formulation of valproate result in decreased formations of minor
      metabolites including 4-en, the most toxic metabolite.

PMID- 12071335
TI  - Suppression of immunoreactive macrophages in atheromatous lesions of rabbits by
      clodronate.
AB  - Bisphosphonates inhibit the development of experimental atherosclerosis and
      decrease the intima-media thickness of human carotid artery. Since arterial
      macrophages have a key role in atherogenesis, we studied whether clodronate, an
      antiatherogenic bisphosphonate, will suppress the appearance of macrophages
      generated by atheromatous process in the rabbit aorta. The atherosclerosis was
      caused in rabbits by means of a high-cholesterol (1%) diet, and the animals were
      treated simultaneously with saline (n = 11) or 25 mg/kg of clodronate disodium
      (n= 12) intravenously twice a week for 6 to 12 weeks. The cholesterol diet for 6
      weeks caused no visible atheromatous plaques in the aorta, but feeding for 6 more
      weeks produced progressively atheromatous lesions. Immunohistochemistry with
      specific antimacrophage antibody showed an intensive accumulation of macrophages
      in the subendothelial layer of the aorta in cholesterol-fed rabbits treated with
      saline or clodronate for 6 weeks. In the aorta of rabbits treated with
      cholesterol diet + saline for 12 weeks, the area of immunoreactive macrophages
      extended from the internal elastic lamina up to the luminal surface of the aorta.
      However, far less immunoreactive macrophages were present in the atheromatous
      regions of the aorta of rabbits medicated with clodronate for 12 weeks; in the
      clodronate-treated animals the macrophages were located closer to the luminal
      surface of the aorta than in controls on saline. No atheromatous lesions and
      macrophages appeared in the aorta of rabbits on standard diet (n = 7). The
      results suggest that clodronate suppresses the appearance of cholesterol
      phagocyting macrophages in arterial walls during atherogenesis.

PMID- 12071337
TI  - Acinar distribution of rat liver arylamine N-acetyltransferase: effect of chronic
      ethanol and endotoxin exposure.
AB  - The expression of most drug-metabolising enzymes is highest in the perivenous
      region of the liver, where drug-induced damage is commonly initiated. Arylamine N
      acetyltransferase plays an important role in activation or detoxification of many
      drugs, carcinogens, pesticides and other xenobiotics, but its acinar distribution
      is unknown. In this study we have analysed the activity of N-acetyltransferase in
      cell lysates obtained from the periportal or perivenous region by digitonin
      treatment during in situ liver perfusion. Livers from control animals were
      compared with rats chronically exposed either to ethanol by liquid diet or to
      lipopolysaccharide (endotoxin) by intravenous administration. The activity of N
      acetyltransferase in the perivenous region was slightly (+ 20%) higher than in
      the periportal region. Although chronic ethanol exposure did not change total
      activity, the acinar distribution was reversed to a higher activity in the
      periportal region. In contrast, chronic endotoxin significantly increased N
      acetyltransferase activity, but did not affect the acinar distribution. This
      increase was counteracted by simultaneous ethanol treatment. N-Acetyltransferase
      activity in perivenous lysates was significantly reduced after the co
      administration of ethanol and endotoxin compared to that after endotoxin alone.
      Thus, the perivenous zonation of liver N-acetyltransferase is moderate compared
      to other transferases or P450 isozymes, and the cellular capacity for N
      acetylation in the perivenous region, where xenobiotic activation to reactive
      intermediates dominates, may be insufficient.

PMID- 12071336
TI  - Cytochrome P450 enzymes contributing to demethylation of maprotiline in man.
AB  - From case reports of patients treated with the tetracyclic antidepressant drug
      maprotiline, it appears that this drug is subject to polymorphic metabolism.
      Thus, we studied formation of the major maprotiline metabolite
      desmethylmaprotiline to identify the human cytochrome P-450 enzymes (CYP)
      involved. In incubations with human liver microsomes from two different donors,
      the substrate maprotiline was used at five different concentrations (5 to 500
      microM). For selective inhibition of CYPs, quinidine (0.5-50 microM; CYP2D6),
      furafylline (0.3-30 microM; CYP1A2), ketoconazole (0.2-20 microM; CYP3A4),
      mephenytoin (20-200 microM; CYP2C19), chlorzoxazone (1-100 microM; CYP2E1),
      sulphaphenazole (0.2-100 microM; CYP2C9) and coumarin (0.2-100 microM; CYP2A6)
      were used. Desmethylmaprotiline concentrations were measured by HPLC, and enzyme
      kinetic parameters were estimated using extended Michaelis-Menten equations with
      non-linear regression. Relevant inhibition of the desmethylmaprotiline formation
      rate was observed in incubations with quinidine, furafylline and ketoconazole
      only. Formation rates of desmethylmaprotiline were consistent with a two enzyme
      model with a high (K(M)=71 and 84 microM) and a low (K(M)=531 and 426 microM)
      affinity site for maprotiline in the two samples, respectively. The high affinity
      site was competitively inhibited by quinidine (K(i,nc) 0.13 and 0.61 microM), the
      low-affinity site was non-competitively inhibited by furafylline (K(i,nc) 0.11
      and 1.3 microM). Thus it appears that CYP2D6 and CYPIA2 contribute to maprotiline
      demethylation. Based on the parameters obtained, for plasma concentrations of 1
      microM 83% (mean) of desmethylmaprotiline formation in vivo is expected to be
      mediated by CYP2D6 while 17% only may be attributed to CYPIA2 activity.

PMID- 12071338
TI  - Diabetes and elimination of antipyrine in man: an analysis of 298 patients
      classified by type of diabetes, age, sex, duration of disease and liver
      involvement.
AB  - Effects of diabetes on hepatic drug metabolism in man has not yet been adequately
      clarified. Two hundred ninety-eight diabetic patients, classified by type of the
      disease, age, gender, duration of therapy and liver involvement, were
      investigated. The antipyrine plasma clearance rate and cytochrome P450 content
      determinations in liver biopsies of subjects with diagnostic liver biopsy were
      used as indices of hepatic drug metabolising capacity. Drug metabolism was
      reduced as a function of age. Antipyrine elimination rate was dependent on the
      type of diabetes (type 1 versus type 2) and gender. Untreated type 1 patients
      eliminated antipyrine rapidly and insulin treatment normalised antipyrine
      elimination (clearance rates 89.5 +/- 20.3 versus 58.8 +/- 17.2 ml/min.;
      P<0.001). Males aged 16-59 years, but not over 60, who responded insufficiently
      to insulin therapy, had a rapid antipyrine elimination, which could be normalised
      by readjustment of insulin administration. Women with insufficient glucose
      control on insulin therapy had antipyrine elimination rate comparable to
      controls. Among type 2 diabetic patients, women metabolised antipyrine normally,
      but men over 40 years of age showed a reduced antipyrine metabolism. IN
      CONCLUSION: Drug metabolism in diabetes is affected by the type of disease,
      therapy and its effectiveness, and age and gender of the patients. These factors
      should be taken into account when evaluating overall drug metabolism in diabetic
      patients. This is especially important when investigating pharmacokinetics of new
      drugs for diabetic patients at different phases of the disease.

PMID- 12071339
TI  - Clomipramine induces the opening of Na+ channels in the frog skin epithelium.
AB  - This paper studies the effect of clomipramine on the electrical parameters of the
      frog skin epithelium. We have found that clomipramine induces: 1) an increase in
      short circuit current that is equivalent to an increase in net Na+ flux, 2) an
      increase in total transepithelial conductance, 3) a depolarisation of the apical
      barrier, and 4) a decrease in the fractional resistance of the apical membrane.
      These results suggest that clomipramine promotes an increase in the sodium
      permeability of the apical barrier by increasing either the concentration of
      amiloride-sensitive Na+ channels or by increasing their individual conductance.
      Using kinetic models, values for the affinity constants for clomipramine and
      amiloride were estimated (K(Clo)=(18.l +/- l.04) x l0(-6) M; K(Amil) = 56 x 10(
      8) M). Identical studies were performed for eel intestinal epithelium and no
      significant changes on the short circuit current were observed.

PMID- 12071340
TI  - A mouse model for the study of factors affecting angiogenesis.

PMID- 12071341
TI  - Inter-laboratory validation of procedures for measuring 8-oxo-7,8
      dihydroguanine/8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA.
AB  - The aim of ESCODD, a European Commission funded Concerted Action, is to improve
      the precision and accuracy of methods for measuring 8-oxo-7,8-dihydroguanine (8
      oxoGua) or the nucleoside (8-oxodG). On two occasions, participating laboratories
      received samples of different concentrations of 8-oxodG for analysis. About half
      the results returned (for 8-oxodG) were within 20% of the median values.
      Coefficients of variation (for three identical samples) were commonly around 10%.
      A sample of calf thymus DNA was sent, dry, to all laboratories. Analysis of 8
      oxoGua/8-oxodG in this sample was a test of hydrolysis methods. Almost half the
      reported results were within 20% of the median value, and half obtained a CVof
      less than 10%. In order to test sensitivity, as well as precision, DNA was
      treated with photosensitiser and light to introduce increasing amounts of 8
      oxoGua and samples were sent to members. Median values calculated from all
      returned results were 45.6 (untreated), 53.9, 60.4 and 65.6 8-oxoGua/10(6) Gua;
      only seven laboratories detected the increase over the whole range, while all but
      one detected a dose response over two concentration intervals. Results in this
      trial reflect a continuing improvement in precision and accuracy. The next
      challenge will be the analysis of 8-oxodG in DNA isolated from cells or tissue,
      where the concentration is much lower than in calf thymus DNA.

PMID- 12071342
TI  - Urinary levels of 8-hydroxydeoxyguanosine as a marker of oxidative damage in road
      cycling.
AB  - We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of eight
      professional cyclists during a 4-day and a 3-week stage races. Monitoring of
      heart rates was used to establish zones corresponding to different intensities of
      exercise. The urinary 8-OHdG excretion, expressed by body weight, increased
      significantly in the first day or the first week of each race, respectively, and
      did not show further increases thereafter. Maximum 8-OHdG levels were reached in
      parallel to longer times spent at high intensities of exercise. Urinary excretion
      of creatinine increased with exercise, and changes in 8-OHdG levels were not
      detected when corrected by creatinine excretion. Serum glutathione concentrations
      did not change significantly at any point during exercise. We conclude that road
      cycling courses with an oxidative damage to DNA, which is sustained as long as
      the exercise is repeated. Both adaptation of antioxidant defenses and a decreased
      capacity to maintain a high intensity of effort may contribute to explain the
      absence of progressive increases in 8-OHdG excretion. The results of this study
      also confirm that the correction procedure using the amount of creatinine
      excreted should not be used when studying effects of exercise on urinary 8-OHdG.

PMID- 12071343
TI  - Protective effects of cimetidine on radiation-induced micronuclei and apoptosis
      in human peripheral blood lymphocytes.
AB  - The radioprotective effects of cimetidine, which has been used clinically as an
      antagonist of H2 receptor, on radiation-induced micronuclei and apoptosis in
      human peripheral blood lymphocytes (PBL) prepared from healthy donors were
      studied. Cells were treated with cimetidine before or after X-irradiation, and
      then cytokinesis-blocked micronucleus assay and flow cytometry for measurement of
      phosphatidylserine externalization were utilized to evaluate the radiation
      induced cytogenetic damage and apoptosis. The protective effect of preirradiation
      treatment of cimetidine on radiation-induced micronuclei was dependent on the
      concentration. The maximum protection rates of cimetidine (1 mM) on frequencies
      of micronuclei were 38.8 and 30.2% for cells treated before and after X
      irradiation (5 Gy), respectively. Protective effects of pre- and post-irradiation
      treatment with cimetidine on radiation-induced early apoptosis and decreased
      activity of caspase-3 were observed. A study of electron paramagnetic resonance
      spin trapping with 5,5'-dimethyl-1-N-oxide revealed that the rate constant of
      cimetidine with radiation-induced OH radicals is about 4.5 x 10(9) l/mol/s.
      Cimetidine did not significantly increase the intracellular concentration of
      glutathione. These results suggest that cimetidine suppresses radiation-induced
      micronuclei and apoptosis via OH radical scavenging and an intracellular
      antioxidation mechanism. Cimetidine appears to be a useful candidate for the
      future development of post-irradiation radioprotectors.

PMID- 12071344
TI  - Plasma carotenoid and malondialdehyde levels in ischemic stroke patients:
      relationship to early outcome.
AB  - An association between ischemic stroke and increased oxidative stress has been
      suggested from animal studies. However, there is a lack of evidence with respect
      to this association in humans. Here, the time course of plasma levels of six
      carotenoids, which are lipophilic micronutrients with antioxidant properties, as
      well as of malondialdehyde (MDA), a marker of lipid peroxidation, was followed in
      ischemic stroke patients. Plasma levels of lutein, zeaxanthin, beta
      cryptoxanthin, lycopene, alpha- and beta-carotene, as well as MDA were measured
      by high-performance liquid chromatography in 28 subjects (19 men and nine women
      aged 76.9+/-8.7 years) with an acute ischemic stroke of recent onset (<24h) on
      admission, after 6 and 24 h, and on days 3, 5, and 7. Carotenoid and MDA levels
      in patients on admission were compared with those of age- and sex-matched
      controls. Plasma levels of lutein, lycopene, alpha- and beta-carotene were
      significantly lower and levels of MDA were significantly higher in patients in
      comparison with controls. Significantly higher levels of MDA and lower levels of
      lutein were found in patients with a poor early-outcome (functional decline)
      after ischemic stroke as compared to patients who remained functionally stable.
      These findings suggest that the majority of plasma carotenoids are lowered
      immediately after an ischemic stroke, perhaps as a result of increased oxidative
      stress, as indicated by a concomitant rise in MDA concentrations. Among the
      carotenoids, only lutein plasma changes are associated with a poor early-outcome.

PMID- 12071345
TI  - Liver necrosis induced by acute intraperitoneal ethanol administration in aged
      rats.
AB  - It is generally agreed that the deleterious pathophysiological effects of ethanol
      are caused, at least partially by an increase in free radical production.
      However, little attention has been directed to the effects of ethanol upon
      elderly organisms. Male Wistar rats at ages 3, 6, 12, 18 and 24 months were
      treated either with a single i.p. dose of 35% ethanol (v/v) at 3 g ethanol/kg
      body weight or an isovolumetric amount of 0.9% saline solution. We then assessed
      the plasma levels of transaminases and hepatic levels of oxidative stress-related
      parameters, followed by liver histological evaluation. The younger rats (3 months
      old) were not affected by the treatment with ethanol with respect to any of the
      studied parameters except for a lowering of total hepatic GSH and an increase in
      hepatic thiobarbituric acid reactants (TBARS) formation, while animals older than
      3 months were increasingly more affected by the treatment. Acute ethanol
      treatment elicited the similar responses to those in the 3 months-old group, plus
      a decrease in the hepatic and plasma levels of beta-carotene and the plasma level
      of alpha-tocopherol, as well as an increase in the activity of plasma
      transaminases. In the 12,18 and 24 months old groups, there was increasing liver
      necrosis. These findings suggest that liver damage induced by acute ethanol
      administration in elderly rats may involve a lack of antioxidants.

PMID- 12071346
TI  - Lysozyme modification by the fenton reaction and gamma radiation.
AB  - A comparative study was performed on lysozyme modification after exposure to
      Fenton reagent (Fe(II)/H2 O2) or hydroxyl radicals produced by y radiation. The
      conditions were adjusted to obtain, with both systems, a 50% loss of activity of
      the modified ensemble. Gamma radiation modified almost all types of amino acid
      residues in the enzyme, with little specificity. The modification order was Tyr >
      Met = Cys > Lys > Ile + Leu > Gly > Pro = Phe > Thr + Ala > Trp = Ser > Arg > Asp
      + Glu, with 42 mol of modified residues per initial mole of native enzyme. In
      contrast, when the enzyme was exposed to the Fenton reaction, only some types of
      amino acids were modified. Furthermore, a smaller number of residues (13.5) were
      damaged per initial mole of enzyme. The order of the modified residues was Tyr >
      Cys > Trp > Met His > Ile + Leu > Val > Arg. These results demonstrate that the
      modifications elicited by these two free radical sources follow different
      mechanisms. An intramolecular free radical chain reaction is proposed to play a
      dominant role in the oxidative modification of the protein promoted by gamma
      radiation.

PMID- 12071347
TI  - Roles of bioavailable iron and calcium in coal dust-induced oxidative stress:
      possible implications in coal workers' lung disease.
AB  - Marked regional differences in prevalence of pneumoconiosis are apparent in the
      US despite comparable dust exposure. In the present study, we examined the
      ability of 28 coal samples to release bioavailable iron (BAI) and calcium, as
      well as other metals such as Cr, Ni, Cu, and Co, from three coal mine regions in
      Utah (UT), West Virginia (WV), and Pennsylvania (PA), respectively. BAI is
      defined as iron (both Fe2+ and Fe3+) released by the coals in 10 mM phosphate
      solution, pH 4.5, which mimics conditions of the phagolysosomes in cells. We
      found that coals from the UT, WV, and PA regions released average levels of BAI
      of 9.6, 4658.8, and 12149 parts per million (ppm, w/w), respectively, which
      correlated well with the prevalence of pneumoconiosis from that region
      (correlation coefficient r = 0.92). The low levels of BAI in the UT coals were
      due to the presence of calcite (CaCO3), which was shown to be preferentially acid
      solubilized before iron compounds. Release of iron by two coal samples from the
      PA and UT regions was further examined in vitro in human lung epithelial A549
      cells. We found that the coal from PA, with a high prevalence of pneumoconiosis,
      released BAI in a dose-dependent manner, both in tissue culture media and in A549
      cells. At 2 microg/cm2, levels of lipid peroxidation induced by the PA coal were
      increased 112% over control cells at 24 h treatment, and were sustained at this
      level for 3 days. The coal from UT, with a low prevalence of pneumoconiosis,
      induced a marginal increase in cellular iron at 5 and 10 microg/cm2 treatments
      and had no effect on lipid peroxidation. Calcium levels in the cells treated with
      the PA and UT coals were 8.6 and 11.5 micromoles/10(6) cells, respectively, and
      were significantly higher than that in the controls (5.3 micromoles/10(6) cells)
      [corrected]. Our results suggest that the differences in the BAI content in the
      coals may be responsible for the observed regional differences in the prevalence
      of pneumoconiosis. Therefore, BAI may be a useful characteristic of coal for
      predicting coal's toxicity.

PMID- 12071348
TI  - Increase in oxidative damage to lipids and proteins in skeletal muscle of uremic
      patients.
AB  - Muscle weakness and reduced exercise capacity are frequent complaints of patients
      with chronic uremia. Several lines of evidence have suggested that chronic uremia
      result in a state of increased oxidative stress. Reactive oxygen species (ROS)
      and free radicals are capable of damaging lipids and proteins but it remains
      unclear whether oxidative damage plays a role in the skeletal myopathy commonly
      seen in chronic uremia. In this cross-sectional study, we compared the levels of
      oxidative damage to proteins and lipids of skeletal muscle from 40 chronic uremic
      patients and 20 age- and sex-matched healthy subjects. Protein carbonyls were
      determined by a spectrophotometric method to assess the oxidative damage to
      proteins. Our results showed that the mean content of protein carbonyls in
      skeletal muscles was significantly elevated in the hemodialysis patients (3.78+/
      0.14 nmol of 2,4-dinitrophenyl-hydrazone per mg of protein) as compared to
      healthy controls (2.97+/-0.28 nmol per mg of protein, p = 0.017 vs normal
      controls). In addition, we found that the mean malondialdehyde (MDA) level was
      also significantly increased in the uremic patients compared to healthy controls.
      Further analysis revealed that there was an age-dependent increase in both
      oxidative damages in these patients. Regression analysis between plasma protein
      carbonyl and MDA levels showed a significant correlation between these two
      parameters (r = 0.43, p = 0.002). The finding of increased oxidative damage to
      protein and lipids provide support that oxidative damage may play a role in the
      pathogenesis of skeletal myopathy in chronic uremic patients on hemodialysis.

PMID- 12071350
TI  - A novel method using 8-hydroperoxy-2'-deoxyguanosine formation for evaluating
      antioxidative potency.
AB  - Degenerative diseases such as cancer are induced by oxidative genetic damage.
      Antioxidants can scavenge reactive oxygen species, but to prevent disease, they
      must do so quickly, before the DNA bases are damaged. In the present study, a
      novel method was established for evaluating the potency of antioxidants employing
      2'-deoxyguanosine as a target and 2,2'-azobis(2-amidino-propane) dihydrochloride
      as a reactive oxygen generator. The reaction formed one product linearly with
      time. This product was a novel 8-hydroperoxy-2'-deoxyguanosine (8-OOHdG). Using
      this system, 81 antioxidants occurring in our diet were assayed for activity to
      suppress the formation of 8-OOHdG by high-performance liquid chromatography
      (HPLC). The system was useful for the evaluation of antioxidative potency,
      compared to another method utilizing 1,1-diphenyl-2-picrylhydrazyl (DPPH).
      Further, it was enabled to examine the synergism of antioxidants. The formation
      of 8-OOHdG started only after the antioxidants had been consumed. Ascorbic acid,
      quercetin, and epigallocatechin gallate together delayed the formation by the sum
      total of the delay times of each factor alone. The proposed method is simple and
      easy, and can evaluate which dietary antioxidants inhibit reactive oxygen species
      more quickly than the DNA bases are damaged.

PMID- 12071349
TI  - Glial fibrillary acidic protein is greatly modified by oxidative stress in
      aceruloplasminemia brain.
AB  - Aceruloplasminemia is an autosomal recessive disorder of iron metabolism caused
      by mutations in the ceruloplasmin (Cp) gene. The neuropathological hallmark of
      this disease is intracellular iron overload, which is thought to lead to neuronal
      cell death through increased oxidative stress. We evaluated and characterized
      protein oxidation in the brain of a patient with this disease. The protein
      carbonyl content in the cerebral cortex of the patient was elevated compared to
      controls. Furthermore, peptide mass fingerprinting and partial amino acid
      sequencing identified glial fibrillary acidic protein (GFAP) as the major
      carbonylated protein in the cerebral cortex of the patient. In conjunction with
      the facts that Cp mainly localizes to astrocytes in the central nervous system
      and that astrocytes are loaded with much more iron than neurons in the cerebral
      cortex, our findings indicate that Cp deficiency may primarily damage astrocytes.
      We speculate that the dysfunction of astrocytes may be causatively related to
      neuronal cell loss in aceruloplasminemia.

PMID- 12071351
TI  - Photoactivation of phthalocyanine-loaded low density lipoproteins induces a local
      oxidative stress that propagates to human erythrocytes: protection by caffeic
      acid.
AB  - Toxic effects imposed to human erythrocytes by low density lipoproteins carrying
      phthalocyanines used in photodynamic therapy (PDT) of tumors are described. This
      study was aimed at evaluating cytotoxic effects induced by reactive species
      produced locally in photosensitizer-loaded lipoproteins and further transferred
      to the cells. The experimental set up designed to examine these interactions
      starts with the loading of human plasma with the photosensitizer, the subsequent
      rapid purification and dialysis of the LDL fraction and incubation with human
      erythrocytes. This experimental model was assessed by following leakage of
      endogenous K+ from cells, electrochemical detection of oxygen, spectroscopic
      determination of conjugated dienes, phthalocyanine, SH groups and hemoglobin,
      analysis of fatty acids by gas chromatography and identification of a-tocopherol
      by HPLC. Photosensitizer-loaded lipoproteins become more susceptible to
      oxidation, exhibiting shorter lag phases of lipid oxidation, higher rates of
      oxidation and increased loss of endogenous alpha-tocopherol when challenged with
      peroxyl radicals and copper, as compared with native lipoproteins from the same
      plasma sample. Incubation of photosensitized lipoproteins with erythrocytes under
      light (>560 nm) results in a sigmoidal efflux of K+ followed by hemolysis. The
      phenolic antioxidant caffeic acid inhibits lipoprotein oxidation induced by
      peroxyl radicals, either in native or photosensitizer-loaded fractions, delays
      hemolysis of erythrocytes and partially prevents membrane loss of SH groups in
      ghosts, but not the efflux of K+. Mechanistically, a chain lipid peroxidation
      reaction does not participate in the toxic effects to cells but a specific pool
      of membrane SH groups sensitive to caffeic acid is likely to be involved. This
      study suggests that an oxidative stress occurring locally in phthalocyanine
      loaded low density lipoproteins may further induce cytotoxic effects by targeting
      specific SH groups at the cell membrane level. The physiological relevance of
      these findings and the beneficial use of antioxidants are discussed in the
      context of PDT.

PMID- 12071352
TI  - Antioxidant and pro-oxidant effect of the thiolic compounds N-acetyl-L-cysteine
      and glutathione against free radical-induced lipid peroxidation.
AB  - The antioxidant ability of thiol compounds has been the subject of much of the
      current research about oxidative stress. The direct scavenging of hydroxyl
      radicals by thiols has been suggested as their protection mechanisms.
      Nevertheless, the interaction of thiols with reactive radicals can generate thiyl
      radicals, which, in turn, may impart a pro-oxidant function. The purpose of this
      study has been to establish the effect of the thiol compounds N-acetyl-L-cysteine
      (NAC) and glutathione (GSH) against the peroxidative processes involving membrane
      lipids. The results obtained support the ability of NAC and GSH to suppress the
      2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH)-dependent or to enhance the
      Fe2+/H2O2-dependent oxidative actions. The evaluation of thiobarbituric acid
      reactive substances (TBARS) production, the study of the influence of oxidants on
      membrane fluidity and the measurements of the changes in the fluorescence of
      bilayer probes, such as 3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid
      (DPH-PA), have shown the antioxidant and pro-oxidant effects of both NAC and GSH.
      Also their dependence on the nature of the radicals generated by the oxidative
      systems used has been shown. The use of ESR spectroscopy has allowed us to
      establish the ability of these compounds to scavenge the AAPH-derived radicals,
      to determine the formation of thiyl radicals in the iron-mediated oxidation and
      to evaluate the enhanced production of hydroxyl radicals by NAC and GSH.

PMID- 12071353
TI  - Serum malondialdehyde correlates with therapeutic efficiency of high activity
      antiretroviral therapies (HAART) in HIV-1 infected children.
AB  - Serum malondialdehyde (MDA) levels are increased in human immunodeficiency virus
      (HIV)-infected children, as it happens also in infected adult individuals.
      Introduction of high activity antiretroviral therapy (HAART) has promoted an
      intense decline in morbidity and mortality of these patients. Here we present
      data on the effect of HAART on serum MDA of HIV+ children and compare them with
      levels prior to HAART. MDA levels reflect, as other markers do, the HAART-induced
      clinical improvement and probably also the pro-oxidant/antioxidant side effects
      of the different drugs used. The results herein allow the proposal of including
      serum MDA levels as an additional parameter for the clinical management of HIV+
      children.

PMID- 12071355
TI  - Melatonin prevents cyclosporine-induced nephrotoxicity in isolated and perfused
      rat kidney.
AB  - Cyclosporine A (CsA) is a potent and effective immunosuppressive agent, but its
      action is frequently accompanied by severe renal toxicity. The precise mechanism
      by which CsA causes renal injury is not known. Reactive oxygen species (ROS) have
      been shown to play a role, since CsA-induced renal lipid peroxidation is
      attenuated in vivo and in vitro by the concomitant administration of antioxidants
      such as vitamin E. We show here the effect of the antioxidant melatonin (MLT), a
      hormone produced by the pineal gland during the dark phase of the circadian
      cycle, in a model of CsA nephrotoxicity in the isolated and perfused rat kidney.
      Kidneys isolated from rats were divided into seven groups. At the end of
      perfusion, malondialdehyde and 4-hydroxyalkenals (MDA + 4-HDA), metabolites of
      nitric oxide NO2- + NO3- were measured and histopathological examination was
      performed. CsA treatment induced a significant increase in MDA + 4-HDA while not
      affecting the nitric oxide metabolite level. MLT remarkably prevented glomerular
      collapse and tubular damage as revealed by morphometric analysis. Our study
      suggests that lipid peroxidation is an early important event in the pathogenesis
      of CsA nephrotoxicity and that MLT is able to protect kidneys from CsA at a
      relatively low concentration.

PMID- 12071354
TI  - PGE1 protection against apoptosis induced by D-galactosamine is not related to
      the modulation of intracellular free radical production in primary culture of rat
      hepatocytes.
AB  - D-galactosamine (D-GalN) toxicity is a useful experimental model of liver failure
      in human. It has been previously observed that PGE1 treatment reduced necrosis
      and apoptosis induced by D-GalN in rats. Primary cultured rat hepatocytes were
      used to evaluate if intracellular oxidative stress was involved during the
      induction of apoptosis and necrosis by D-GalN (0-40mM). Also, the present study
      investigated if PGE1 (1 microM) was equally potent reducing both types of cell
      death. The presence of hypodiploid cells, DNA fragmentation and caspase-3
      activation were used as a marker of hepatocyte apoptosis. Necrosis was measured
      by lactate dehydrogenase (LDH) release. Oxidative stress was evaluated by the
      intracellular production of hydrogen peroxide (H2O2), the disturbances on the
      mitochondrial transmembrane potential (MTP), thiobarbituric-reacting substances
      (TBARS) release and the GSH/GSSG ratio. Data showed that intermediate range of D
      GalN concentrations (2.5-10mM) induced apoptosis in association with a moderate
      oxidative stress. High D-GalN concentration (40 mM) induced a reduction of all
      parameters associated with apoptosis and enhanced all those related to necrosis
      and intracellular oxidative stress, including a reduction of GSH/GSSG ratio and
      MTP in comparison with D-GalN (2.5-10 mM)-treated cells. Although PGE1 reduced
      apoptosis induced by D-GalN, it was not able to reduce the oxidative stress and
      cell necrosis induced by the hepatotoxin in spite to its ability to abolish the
      GSH depletion.

PMID- 12071357
TI  - Infant death and childhood cancer reductions after nuclear plant closings in the
      United States.
AB  - Subsequent to 1987, 8 U.S. nuclear plants located at least 113 km from other
      reactors ceased operations. Strontium-90 levels in local milk declined sharply
      after closings, as did deaths among infants who had lived downwind and within 64
      km of each plant. These reductions occurred during the first 2 yr that followed
      closing of the plants, were sustained for at least 6 yr, and were especially
      pronounced for birth defects. Trends in infant deaths in proximate areas not
      downwind, and more than 64 km from the closed plants, were not different from the
      national patterns. In proximate areas for which data were available, cancer
      incidence in children younger than 5 yr of age fell significantly after the
      shutdowns. Changes in health following nuclear reactor closings may help
      elucidate the relationship between low-dose radiation exposure and disease.

PMID- 12071356
TI  - The 1997 haze disaster in Indonesia: its air quality and health effects.
AB  - In this study, the authors assessed air quality and health effects of the 1997
      haze disaster in Indonesia. The authors measured carbon monoxide, carbon dioxide,
      sulfur dioxide, nitrogen dioxide, ozone, particulate matter with diameters less
      than or equal to 10 microm, inorganic ions, and polycyclic aromatic hydrocarbons.
      The authors also interviewed 543 people and conducted lung-function tests and
      determined spirometric values for these individuals. Concentrations of carbon
      monoxide and particulate matter with diameters less than or equal to 10 microm
      reached "very unhealthy" and "hazardous" levels, as defined by the Pollution
      Standards Index. Concentrations of the polycyclic aromatic hydrocarbons were 6-14
      times higher than levels in the unaffected area. More than 90% of the respondents
      had respiratory symptoms, and elderly individuals suffered a serious
      deterioration of overall health. In multivariate analysis, the authors determined
      that gender, history of asthma, and frequency of wearing a mask were associated
      with severity of respiratory problems. The results of our study demonstrate the
      need for special care of the elderly and for care of those with a history of
      asthma. In addition, the use of a proper mask may afford protection.

PMID- 12071358
TI  - Melanoma incidence and frequency modulation (FM) broadcasting.
AB  - The incidence of melanoma has been increasing steadily in many countries since
      1960, but the underlying mechanism causing this increase remains elusive. The
      incidence of melanoma has been linked to the distance to frequency modulation
      (FM) broadcasting towers. In the current study, the authors sought to determine
      if there was also a related link on a larger scale for entire countries. Exposure
      time-specific incidence was extracted from exposure and incidence data from 4
      different countries, and this was compared with reported age-specific incidence
      of melanoma. Geographic differences in melanoma incidence were compared with the
      magnitude of this environmental stress. The exposure-time-specific incidence from
      all 4 countries became almost identical, and they were approximately equal to the
      reported age-specific incidence of melanoma. A correlation between melanoma
      incidence and the number of locally receivable FM transmitters was found. The
      authors concluded that melanoma is associated with exposure to FM broadcasting.

PMID- 12071359
TI  - Air pollution and hospital emergency room admissions for chronic obstructive
      pulmonary disease in Valencia, Spain.
AB  - The short-term relationship between levels of air pollution and emergency room
      admissions for chronic obstructive pulmonary disease was assessed in Valencia,
      Spain. The design was an ecological time-series study in which daily variation in
      air pollution was related to emergency chronic obstructive pulmonary disease
      visits to one of the city's hospitals. The pollutants under investigation were
      Black Smoke, sulfur dioxide, nitrogen dioxide, carbon monoxide, and ozone. The
      degree of association was analyzed with Poisson autoregressive regression, for
      which trend, seasonal patterns, temperature, humidity, days of the week, and
      incidence of influenza were controlled. Increases of 10 microg/m3 in ozone levels
      (lag 5) and of 1 mg/m3 in carbon monoxide (lag 1) were associated with increases
      of 6.1% (95% confidence interval [CI] = 2.2%, 10.1%) and of 3.9% (95% CI = 1.4%,
      6.6%), respectively, in the expected chronic obstructive pulmonary disease cases.
      There was no significant association for the remainder of the pollutants. The
      described effects persisted even when the authors used models of differing
      specifications and when generalized additive models were used. The authors
      concluded that the results of this investigation, together with results of
      earlier research, demonstrate the significant effect of pollution on various
      health indicaors within Valencia.

PMID- 12071360
TI  - Correlation between asthma and climate in the European Community Respiratory
      Health Survey.
AB  - The European Community Respiratory Health Survey, performed during 1991-1993,
      found a remarkable geographical variability in the prevalence of asthma and
      asthma-like symptoms in individuals aged 20-44 yr. The highest values occurred in
      the English-speaking centers. In the present investigation, the ecological
      relationship between climate and symptom prevalence was evaluated in the 48
      centers of the European Community Respiratory Health Survey. Meteorological
      variables were derived from the Global Historical Climatology Network and were
      averaged over an 11-yr period (i.e., 1980-1990). Respiratory symptom prevalence
      was directly related to temperature in the coldest month and was related
      inversely to the temperature in the hottest month. Warm winters and cool summers
      are features of oceanic climate found in most English-speaking centers of the
      European Community Respiratory Health Survey (i.e., England, New Zealand, and
      Oregon). In conclusion, climate can account for significant geographic
      variability in respiratory symptom prevalence.

PMID- 12071361
TI  - Diesel particles are taken up by alveolar type II tumor cells and alter cytokines
      secretion.
AB  - Diesel exhaust particles can reach the alveolar space and interact with alveolar
      type II cells. The authors investigated whether diesel exhaust particles lead to
      an internalization process and alter the production of proinflammatory cytokines,
      such as interleukin-8 and granulocyte macrophage-colony-stimulating factor by
      human alveolar type II cells. Cells from the human lung epithelial cell line A
      549 were incubated with diesel exhaust particles or with inert particles for
      different periods of time. Phagocytosis was studied with electron microscopic
      analysis and flow cytometry. Cytokines were quantified in supernatants with
      enzyme-linked immunosorbent assay. Both diesel exhaust particles and inert
      particles were similarly engulfed by alveolar type II cells. Diesel exhaust
      particles induced a dose- and a time-dependent increase in granulocyte macrophage
      colony-stimulating factor release and a transient inhibition of interleukin-8
      release, but inert particles did not. Diesel exhaust particles were taken up by
      alveolar type II cells, and they altered cytokine production. Alveolar type II
      cells, therefore, may represent a target site for the deleterious effects of
      diesel exhaust particles.

PMID- 12071362
TI  - Evidence for a deployment-related Gulf War syndrome by factor analysis.
AB  - To identify a syndrome unique to Gulf War veterans, the authors applied an
      exploratory factor analysis to the 47-symptom correlation matrix of 10,423 Gulf
      War and 8,960 non-Gulf War veteran respondents. A separate factor analysis was
      performed for Gulf War and non-Gulf War veterans, and the resulting 6 factors
      were compared between the 2 groups. Five of the factors were very similar in the
      2 groups; however, 1 of the factors in the Gulf War group, but not the non-Gulf
      War group, contained a cluster of symptoms consistent with neurological
      impairment. Symptoms specific to this factor were blurred vision, loss of
      balance/dizziness, tremors/shaking, and speech difficulty. The Gulf War veterans
      who had all of the aforementioned symptoms (n = 277) also reported exposures to
      several putative risk factors at a rate 3 or more times higher than other Gulf
      War veterans. This finding suggests a possible syndrome related to Gulf War
      deployment, which requires objective supporting clinical evidence.

PMID- 12071363
TI  - Cadmium levels in the lung, liver, kidney cortex, and urine samples from
      Australians without occupational exposure to metals.
AB  - The authors undertook this study to assess levels of cadmium exposure in the
      general population. Samples of lung, liver, and kidney were obtained from 61
      cadavers (43 males, 18 females; 2-89 yr of age, mean age = 38.5 yr) who died from
      accidental causes and who were subject to postmortem examinations at the John
      Tonge Centre for Forensic Sciences, Queensland Health Scientific Services,
      Brisbane, Australia, in 1997 and 1998. Samples of bladder urine were also
      obtained from 22 cadavers. Tissue and urine samples were analyzed for cadmium,
      zinc, and copper with inductively coupled plasm (ICP) mass spectrometry. The
      overall mean values for cadmium in the lung, liver, and kidney cortex samples
      were 0.13, 0.95, and 15.45 microg/gm wet tissue weight. The average renal cadmium
      level in subjects with high lung-cadmium levels (n = 13) was 6 microg/gm wet
      tissue weight higher than that of similarly aged subjects who had medium lung
      cadmium levels (n = 30). In females, the average level of cadmium in the liver
      was 74% greater than in males, and the average liver cadmium in females with high
      lung-cadmium levels was 100% higher than in males in the same age range who had
      the same high lung-cadmium levels. Renal cadmium accumulation tended to be
      greater in females than in males who were in the same age range and who had
      similar lung-cadmium levels, a result that suggested that there was a higher
      absorption rate of cadmium in females. The mean value for a urinary cadmium
      excretion of 2.30 microg/gm creatinine was found in a subset of samples that had
      a mean age of 39 yr and a renal cortex cadmium concentration of 18.6 microg/gm
      wet tissue weight. Urinary cadmium excretion rates were correlated more strongly
      with lung and kidney cadmium content than with age or liver cadmium levels. The
      results suggest that urinary cadmium excretion may be increased in smokers and
      could provide some estimate of body cadmium burdens in future Australian
      epidemiological studies.

PMID- 12071364
TI  - Janus revisited, molds again.

PMID- 12071365
TI  - Suspended onion particles and potential corneal injury in onion harvesters.
AB  - The authors suspected that suspended onion particles contributed to corneal
      ulcers in onion harvesters in southern Taiwan. In the present study, the authors
      used manikins to study suspended onion particles in fields in an effort to
      simulate typical conditions experienced by onion harvesters. An animal eye
      exposure simulation study was also performed by the authors, who impacted
      suspended soil grains or onion particles onto the corneas of guinea pigs via
      aerosol generated from the Palas dispersion nozzle. The average size of 25.9 pm
      for suspended particles collected during the digging of onions was the largest
      one of those for various harvesting activities. Some onion skin flakes were found
      in samples obtained from gathering and packing activities; the typical flake size
      was approximately 3.5 x 2.5 mm2. The results of the animal study indicated that
      the size of soil grains has a demonstrable effect on the severity of corneal
      injury (p = .009). With respect to onion skin flakes, wind velocity was also
      associated significantly with the occurrence of corneal injury (p = .0004). A
      wind velocity threshold of 7 m/sec is recommended for the maintenance of safety,
      and if the wind speed exceeds this threshold level, workers should not engage in
      harvesting activities. Furthermore, use of appropriately designed goggles is
      necessary for the protection of onion harvesters who work in high-wind
      conditions.

PMID- 12071366
TI  - Concentration of metals and other elements in the hair of Easter Islanders.

PMID- 12071368
TI  - Reflections on science III. A lifetime of looking.

PMID- 12071367
TI  - Thyrotoxicosis among Hanford, Washington, Downwinders: a community-based health
      survey.
AB  - Sixty cases of thyrotoxicosis (including hyperthyroidism, Graves' disease, and
      toxic goiter), an unexpectedly large number compared with general population
      data, were reported in a voluntary health survey that included a period of
      approximately 50 yr, with 801 self-defined "Downwinders" who had lived near the
      Hanford, Washington, nuclear facility. In another self-selected group of medical
      patients (n = 423) who were examined over the same time period, only 2 cases of
      thyrotoxicosis were identified. Evidence is presented that suggests that the
      effects of bias from self-selection likely did not account for the magnitude of
      the apparent excess of thyrotoxicosis cases in the present study population. The
      findings are consistent with those of other studies, as well as with the
      hypothesis of an association of thyrotoxicosis with exposures to radioiodine.

PMID- 12071369
TI  - Mesiodistal size of deciduous teeth in subjects with unilateral cleft lip and
      palate.
AB  - The aim of this study was to investigate whether there was an association between
      presence of a cleft and reduced size of deciduous tooth on the cleft side. In
      this investigation, 58 study models of patients with unilateral cleft lip and
      palate with deciduous dentition were analyzed. The largest mesiodistal dimension
      of deciduous teeth was measured by a sliding caliper. The size of the same teeth
      on the side of the cleft and on the non-cleft side was compared. The results of
      the investigation were statistically analyzed. A difference between the genders
      was found. In the sample of boys the lateral deciduous incisor and the second
      deciduous molars on the cleft side were smaller than those on the non-cleft side,
      while in girls the central and lateral deciduous incisors were smaller on the
      cleft side than on the non-cleft side. It was concluded that the presence of a
      unilateral cleft lip and palate was associated with smaller tooth size.

PMID- 12071370
TI  - Immunolocalization of urokinase and its receptor in prematurely fused cranial
      sutures of infants.
AB  - In cranial sutural samples derived from five children with premature cranial
      suture fusion we have performed immunostaining for the urokinase plasminogen
      activator (uPA) and urokinase receptor (uPAR). We have found a strong reactivity
      for cell- or matrix-bound uPA and uPAR in the sutural connective tissue and
      associated with the osteoblasts and osteocytes lining the calvarial bone. The
      sutural tissue itself showed a banding with different intensity of urokinase and
      uPAR staining concerning connective tissue. It is proposed that the components of
      the plasminogen activating system are involved in tissue turnover of sutural
      tissue and in sutural growth.

PMID- 12071372
TI  - Orthodontic education and the Board certification process.

PMID- 12071371
TI  - A longitudinal evaluation of pulpal pain during orthodontic tooth movement.
AB  - OBJECTIVES: To examine the longitudinal changes in pulpal sensitivity to
      electrical stimulation and the relationship to pulpal sensitivity as measured by
      electrical stimulation and subjective reports of tooth pain after archwire
      insertion. DESIGN: Non-randomized, prospective trial, with matched controls.
      SETTING AND SAMPLE POPULATION: Regional Clinical Dental Research Center at the
      University of Washington School of Dentistry. Eighteen adult subjects of age 13
      37 years. Nine experimental subjects planned for orthodontic treatment. Nine
      control subjects matched for gender and age who did not have orthodontic
      treatment. EXPERIMENTAL VARIABLE: Fixed orthodontic appliances and initial
      archwire placement in experimental subjects compared with 'no treatment' control
      subjects. OUTCOME MEASURE: Subjective assessments of orthodontic tooth pain were
      made using visual analogue scales. Electrically evoked detection and pain
      thresholds were determined using a computer-controlled tooth stimulator. Data
      were gathered at five time points: after bracket placement (baseline), 1 h after
      placement of initial archwires, 1 day after archwire placement, 1 week after
      archwire placement, and 1 month after archwire placement. Comparable time
      intervals were used for the 'no treatment' control subjects. RESULTS: Subjective
      ratings of treatment-evoked tooth pain in the experimental group were the
      greatest at the post-archwire day 1 observation and progressively decreased for
      the remaining observations. Control subjects reported little pain at any of these
      observation times. The detection and pain threshold changes from baseline showed
      no statistical differences over time or between groups. While not statistically
      significant, a trend was noted where reports of greater orthodontic tooth pain
      were associated with increased sensitivity to electrical stimulation (i.e. lower
      detection and pain thresholds). CONCLUSION: Orthodontic patients experience
      significant pain and discomfort 1 day after initial archwire placement (i.e.
      activation). Future research should investigate whether self-reports of treatment
      evoked tooth pain intensity are associated with pulpal sensitivity.

PMID- 12071373
TI  - Morphospatial analysis of soft-tissue profile in patients with Class II Division
      1 malocclusion treated using twin block appliances: geometric morphometrics.
AB  - OBJECTIVES: To study soft-tissue profile changes in patients treated with twin
      block appliances (TBA) for the correction of Class II division 1 malocclusion.
      The null hypothesis is that soft-tissue profiles do not show any significant
      improvements associated with TBA treatment. DESIGN: Longitudinal, retrospective.
      SETTING AND SAMPLE POPULATION: Scotland, UK, using lateral cephalographs of 46
      consecutive, prepubertal children (aged 9-11 years) and 55 adolescents (aged 12
      14 years) obtained from an orthodontic practice. EXPERIMENTAL VARIABLE: The
      prepubertal children underwent = 13 months of TBA treatment, while the
      adolescents underwent = 22 months of treatment. OUTCOME MEASURES: Configurations
      of 13 digitized homologous landmarks of pre- and post-treatment soft-tissue
      facial profiles were compared using cephalometry, Euclidean distance matrix
      analysis (EDMA) and thin plate spline (TPS) analysis. RESULTS: Cephalometry
      showed that height increases associated with the TBA were in the labiomental
      areas, and the most significant height decreases were seen in the lip regions.
      The results of EDMA also indicated significant changes (P < 0.05). The distance
      between the lips decreased by >5%, with increases in length in the labiomental
      region. The TPS analysis showed the soft-tissues of the mandibular complex being
      displaced anteroinferiorly, with anterior displacement of the landmarks of the
      lip region. These changes showed that the lips were brought into closer proximity
      with each other, permitting a functional oral seal. Moreover, the labiomental
      groove became less pronounced, reflecting the underlying dento-alveolar
      correction. CONCLUSION: Demonstrable improvements in soft-tissue facial profile
      may be associated with TBA treatment.

PMID- 12071374
TI  - Transforming growth factor-beta3 (Tgf-beta3) down-regulates Tgf-beta3 receptor
      type I (Tbetar-I) during rescue of cranial sutures from osseous obliteration.
AB  - Appropriate biochemical regulation of intramembranous bone growth from sutures is
      necessary to achieve correct craniofacial morphology. Failure to form sutures
      (agenesis) or to maintain sutures in their unossified state (craniosynostosis)
      can result in severe facial dysmorphology. Several factors such as Twist, Msx2,
      fibroblast growth factors (Fgfs), bone morphogenetic proteins (Bmps) and
      transforming growth factors-beta (Tgf-betas) regulate suture patency, likely by
      interacting with one another. Tgf-beta2 and Tgf-beta3 use the same cell surface
      receptors, yet have opposite effects on suture patency, cellular proliferation
      and apoptosis within the suture. One possible mechanism by which Tgf-beta3
      rescues sutures from obliteration is by regulating the ability of suture cells to
      respond to Tgf-beta2. As Tgf-beta3 does not regulate protein levels of Tgf-beta2
      in sutures, Tgf-beta3 could regulate tissue responsiveness to Tgf-beta2 by
      regulating Tgf-beta2 access to receptors. Tgf-beta3 is a more potent competitor
      than Tgf-beta2 for cell surface receptors, so it is proposed that Tgf-beta3 binds
      to and down-regulates Tgf-beta receptor type I (Tbetar-I) expression by suture
      cells. This down-regulation would limit the ability of cells to respond to all
      Tgf-betas, including Tgf-beta2. To test this hypothesis, an in vitro culture
      model was used in which fetal rat sutures either remain patent or are induced to
      fuse when cultured in the presence or absence of dura mater, respectively. Tgf
      beta3 was added to cultured calvaria and changes in the number of receptor
      positive cells within the suture were established. Data were compared with that
      seen in control sutures and in normal sutures in vivo. It was found that the
      numbers of cells expressing Tbetar-I within the suture matrix increased over time
      in sutures remaining patent. Osteoblastic cells lining the bone fronts on either
      side of sutures were Tbetar-I positive during early morphogenesis, but these
      numbers declined as sutures fused, both in vivo and in vitro. Addition of Tgf
      beta3 to calvaria in culture decreased the number of Tbetar-I expressing cells in
      both fusing and non-fusing sutures, with dramatic decreases in the numbers of
      osteoblasts expressing Tbetar-I.

PMID- 12071375
TI  - Regional size differences in four commonly used cephalometric atlases: the Ann
      Arbor, Cleveland (Bolton), London (UK), and Philadelphia atlases compared.
AB  - OBJECTIVE: To explore regional influence on size in roentgenocephalometric
      atlases. DESIGN: Comparisons of the size of 10 linear distances in four atlases
      from geographically different regions, i.e. Ann Arbor Michigan, Cleveland Ohio,
      Philadelphia Pennsylvania and London, UK. DISTANCES COMPARED: anterior cranial
      base length (S-N), posterior cranial base length (S-Ba), total face height (N
      Me), upper face height (N-ANS), lower face height (ANS-Me), mandibular diagonal
      (Ar-Gn), corpus length (Go-Pg), ramus height (Ar-Go), maxillary length (SNP-SNA),
      posterior face height (S-Go). RESULTS: Correction for enlargement appeared to be
      a necessity before distances could be compared. After correction for enlargement,
      the anterior cranial base was longest in Ann Arbor, lower face height smallest in
      Cleveland (Bolton standards) and the maxilla was shortest in Philadelphia.
      CONCLUSION: Regional size variance in cephalometric data cannot be ignored.

PMID- 12071376
TI  - A less-invasive approach with orthodontic treatment in Beckwith-Wiedemann
      patients.
AB  - The Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder, linked to an
      alteration on the short arm of chromosome 11 that comprises multiple congenital
      anomalies. Macroglossia is the predominant finding, with subsequent protrusion of
      dentoalveolar structures, which results in a protruding mandible, anterior open
      bite, abnormally obtuse gonial angle and increased mandibular length. A less
      invasive treatment with orthopaedic appliances in a patient with early tongue
      reduction is presented. This work summarizes the oral signs linked to
      macroglossia, and highlights the influence of macroglossia on mandibular growth
      structures. In our opinion, glossotomy could be carried out in the paediatric
      patient as a preventive measure in that it curbs the tongue's influence on
      skeletal growth and dramatically reduces the duration and extensiveness of
      subsequent treatment.

PMID- 12071377
TI  - Pharmacology and midwifery are not mutually exclusive.

PMID- 12071378
TI  - Pharmaceutical therapy in midwifery practice: a culturally competent approach.
AB  - The profession of midwifery can be part of the solution in America's quest for a
      culturally sensitive and competent health care system. Midwives who are familiar
      with a variety of health-related cultural beliefs and practice culturally
      sensitive inquiry, particularly when using pharmaceutical therapies, can
      effectively understand and respond to the cultural complexities that impact a
      client's health. This article describes needed cultural competencies, reviews a
      variety of health-related cultural beliefs, and relates how these beliefs impact
      the use and acceptability of pharmaceutical therapies. Specific examples related
      to culturally sensitive inquiry are discussed along with recommendations.

PMID- 12071379
TI  - Estrogen: physiology, pharmacology, and formulations for replacement therapy.
AB  - Estrogen is the central component in 6 of the 100 most widely prescribed
      medications in the United States today. This steroid has several therapeutic uses
      including contraceptive applications, treatment of menopausal symptoms, and the
      prevention of osteoporosis. A wide variety of estrogen replacement therapy (ERT)
      and estrogen plus progestational hormonal replacement therapy (HRT) preparations
      are available. In addition, there are an increasing number of products with
      estrogenic properties that are being promoted as alternatives to drugs containing
      estrogen, such as phytoestrogens and selective estrogen receptor modifiers
      (SERMs). This article reviews the physiology of estrogenic effects, estrogen
      metabolism, and the pharmacokinetics of marketed preparations.

PMID- 12071381
TI  - Progestin contraceptives.
AB  - Progestin contraceptives offer unique advantages, allowing the clinician to
      tailor optimum regimens for selected women. This article reviews the various
      progestational drugs, regimens, and delivery systems available presently and in
      development, with reference to the clinical benefits and limitations of each
      method.

PMID- 12071380
TI  - Contraceptive applications of estrogen.
AB  - Estrogens are a primary component of several contraceptive methods: combined oral
      contraceptive pills, a combined injectable contraceptive, the combined
      contraceptive vaginal ring, the combination transdermal contraceptive patch, and
      combined emergency contraceptive pills. Contraceptive formulations that contain
      estrogen are referred to as combined contraceptives because they also contain
      some form of progestin. This article reviews the contraceptive methods containing
      estrogen, beginning with a discussion of combined oral contraceptive pills.
      Formulations and clinical management, mechanisms of action, noncontraceptive
      benefits of use, therapeutic uses in addition to contraception, side effects,
      contraindications to use, and drug-drug interactions are described. Information
      follows about the newer combined contraceptive products including the injection,
      vaginal ring, and patch. Finally, combined emergency contraceptive pills are
      reviewed. Thorough knowledge of the contraceptive methods containing estrogen
      enables clinicians to provide expert care for women using these products.

PMID- 12071382
TI  - Pharmacologic management of common lower respiratory tract disorders in women.
AB  - In a primary care setting, midwives collaboratively manage common lower
      respiratory conditions that require pharmacologic therapy. Current knowledge
      about the indications, use, adverse effects, and potential side effects of these
      medications is essential. This article reviews the drugs most frequently used for
      the outpatient treatment of asthma, tuberculosis, pneumonia, and bronchitis
      (acute and chronic) in adults. Recommendations from the Centers for Disease
      Control and Prevention guidelines and professional societies are presented. Drug
      pharmacology and adverse effects are discussed in detail.

PMID- 12071384
TI  - Nutriceuticals and cardiovascular health in women.
AB  - This article examines the evidence on use of nutriceuticals for promotion of
      cardiovascular health in women. Studies elucidating mechanism of action,
      physiologic effects of antioxidant vitamins, carotenoids, flavonoids, and garlic
      are presented. Emerging evidence for the impact of homocysteine on cardiovascular
      risk factors and events and evidence for the impact of different types of fats on
      cardiovascular markers are reviewed. The effects of a heart-healthy diet are
      supported in this review of research on nutriceuticals. Primary prevention of
      cardiovascular disease in women is clearly efficacious, and this article
      summarizes information to be shared with women about nutriceuticals and diet to
      better enable decisions they can adopt to promote cardiovascular health.

PMID- 12071383
TI  - Antiviral agents in women's health: pharmacotherapeutics of treating influenza
      and herpes.
AB  - This article updates the practitioner on the pharmacology of antiviral agents.
      The mechanism of action of the six different classifications of antiviral agents
      is described. Because influenza and herpes are the viral infections that are most
      frequently treated in clinical practice, the pharmacotherapeutics of common
      antiviral agents for these infections are described. This includes
      pharmacokinetics, adverse effects, preparations, and dosages. Other
      recommendations related to prescribing and client education surrounding each of
      the pharmaceutical agents is reviewed.

PMID- 12071385
TI  - Clinical bulletin no. 6--January 2002. Abnormal and dysfunctional uterine
      bleeding.

PMID- 12071387
TI  - Management of the third stage of labor: an evidence-based approach.

PMID- 12071386
TI  - Management of the third stage of labor: an evidence-based approach.

PMID- 12071388
TI  - National Abortion Federation (NAF) advertisement for Early Options education
      modules.

PMID- 12071389
TI  - National Abortion Federation (NAF) advertisement for Early Options education
      modules.

PMID- 12071391
TI  - A Wise Birth revisited.

PMID- 12071390
TI  - National Abortion Federation (NAF) advertisement for Early Options education
      modules.

PMID- 12071392
TI  - Evaluation of a shared-work program for reducing assistance provided to supported
      workers with severe multiple disabilities.
AB  - Concern has been expressed recently regarding the need to enhance the performance
      of individuals with highly significant disabilities in community-based, supported
      jobs. We evaluated a shared-work program for reducing job coach assistance
      provided to three workers with severe multiple disabilities in a publishing
      company. Following systematic observations of the assistance provided as each
      worker worked on entire job tasks, steps comprising the tasks were then re
      assigned across workers. The re-assignment involved assigning each worker only
      those task steps for which the respective worker received the least amount of
      assistance (e.g., re-assigning steps that a worker could not complete due to
      physical disabilities), and ensuring the entire tasks were still completed by
      combining steps performed by all three workers. The shared-work program was
      accompanied by reductions in job coach assistance provided to each worker. Work
      productivity of the supported workers initially decreased but then increased to a
      level equivalent to the higher ranges of baseline productivity. These results
      suggested that the shared-work program appears to represent a viable means of
      enhancing supported work performance of people with severe multiple disabilities
      in some types of community jobs. Future research needs discussed focus on
      evaluating shared-work approaches with other jobs, and developing additional
      community work models specifically for people with highly significant
      disabilities.

PMID- 12071393
TI  - Stability of measures of the home environment for families of children with
      severe disabilities.
AB  - The stability of home environment in families of children with severe
      disabilities was investigated. Sixty-four families were assessed at three time
      points regarding aspects of their home environment. Family environment scale,
      home quality rating scale (HQRS) and home observation for measurement of the
      environment scores were collected at 7 and 9 years after the initial assessment.
      A remarkable degree of stability was observed, particularly for the FES. The
      median change score was zero for most subscales; no correlations differed
      significantly between the 7- and 9-year retests. A repeated measures MANOVA found
      a significant change in scores over time for only one subscale of the HQRS but
      none of the 10 FES subscales. Results suggest that, for the FES, administration
      of these measures every 2 years, perhaps less often, would be sufficient in
      longitudinal studies of this population. Internal consistency reliability of the
      FES was lower for these families than in the standardization samples, emphasizing
      the need to validate measures used with special populations.

PMID- 12071394
TI  - Treatment of automatically reinforced object mouthing with noncontingent
      reinforcement and response blocking: experimental analysis and social validation.
AB  - A brief functional analysis indicated the object mouthing of a young girl
      diagnosed with autism was maintained independent of social consequences. Separate
      and combined effects of response blocking and noncontingent reinforcement (with
      preferred stimuli) were then evaluated as treatments for object mouthing.
      Although both interventions were unsuccessful when implemented separately,
      combining them resulted in generalized reductions that were socially valid.

PMID- 12071395
TI  - Factor analysis and norms for parent ratings on the Aberrant Behavior Checklist
      Community for young people in special education.
AB  - The parents of 601 children and adolescents, responding to a mail survey, rated
      their children on the Aberrant Behavior Checklist-Community (ABC-C). Factor
      analysis of ABC-C ratings revealed a factor structure that was similar to the
      original ABC but without the fifth factor (Inappropriate Speech). Coefficients of
      congruence were moderate to large for the four-factor model, and alpha
      coefficients were moderate to high when the original item assignment was imposed.
      Confirmatory factor analysis indicated a modest level of fit with the traditional
      method of scoring the ABC and acceptable fit when the items were coded for
      occurrence (0 or 1). Analysis of subject variables revealed main effects for
      gender on one subscale (Hyperactivity), main effects for age on two subscales
      (Irritability; Hyperactivity), and one main effect for classroom assignment on
      the Stereotypic Behavior subscale. Normative data for parent ratings were
      presented by age and gender combined, gender alone, and age alone. With some
      qualifications, the ABC-C appears to be valid for assessing children in special
      educational settings, although further research is needed on the ABC's factor
      structure in this population.

PMID- 12071396
TI  - The effects of interpolated reinforcement on resistance to extinction in children
      diagnosed with autism: a preliminary investigation.
AB  - Studies on the "interpolation of reinforcement" effect (IRE) suggest that
      switching from an intermittent (INT) to a continuous (CRF) reinforcement schedule
      may result in less resistance to extinction than if extinction had followed INT
      alone. The finding has been examined with both human and animal participants
      using both free- and restricted-operant research preparations with equivocal
      results. In the present study, the IRE was examined in four young children
      diagnosed with autism using a free-operant preparation. Participants were matched
      into pairs and were exposed, in a counterbalanced order, to extinction following
      CRF "interpolated" between INT and extinction, and to extinction following INT
      alone. Resistance to extinction was examined by comparing the number of responses
      emitted during extinction and the number of sessions required to reach an
      extinction criterion. Responding may be less resistant to extinction following
      interpolated CRF reinforcement than following INT alone. Methodological
      refinements necessary for more conclusively demonstrating the IRE are discussed.

PMID- 12071397
TI  - Progress and outcomes for children with autism receiving parent-managed intensive
      interventions.
AB  - Parent-managed behavioral interventions for young children with autism are under
      researched. We analysed data from 66 children served by 25 different early
      intervention consultants. After a mean of 31.6 months of intervention, IQ scores
      had not changed (N = 22). Vineland adaptive behavior scores had increased
      significantly by 8.9 points (N = 21). No children aged >72 months attained normal
      functioning, i.e., IQ > 85 and unassisted mainstream school placement (N = 42).
      Progress for 60 children across 12 months was found for mental age (5.4 months),
      adaptive behavior (9.7 months), and language (5.1 months). The interventions did
      not reproduce results from clinic-based professionally directed programs. The
      effectiveness of the parent-managed intervention model as it has developed and
      the adequacy of professional services in that model are discussed.

PMID- 12071398
TI  - Sequential estimation in line transect surveys.
AB  - This article considers using sequential procedures to determine the amount of
      survey effort required in a line transect survey in order to achieve a certain
      precision level in estimating the abundance of a biological population.
      Sequential procedures are constructed for both parametric and nonparametric
      animal abundance estimators. The criterion used to derive the stopping rules is
      the width of confidence intervals for the animal abundance. For each estimator
      considered, we develop stopping rules based on the asymptotic distributions and
      the bootstrap. A sequential analysis on an aerial survey of the southern bluefin
      tuna indicates substantial saving of survey effort can be made by employment of
      the proposed sequential procedures. This savings of survey effort is also
      observed in a simulation study designed to evaluate the empirical performance of
      the proposed sequential procedures.

PMID- 12071399
TI  - Spatial modeling of wetland condition in the U.S. Prairie Pothole Region.
AB  - We propose a spatial modeling framework for wetland data produced from a remote
      sensing-based waterfowl habitat survey conducted in the U.S. Prairie Pothole
      Region (PPR). The data produced from this survey consist of the area containing
      water on many thousands of wetland basins (i.e., prairie potholes). We propose a
      two-state model containing wet and dry states. This model provides a concise
      description of wet probability, i.e., the probability that a basin contains
      water, and the amount of water contained in wet basins. The two model components
      are spatially linked through a common latent effect, which is assumed to be
      spatially correlated. Model fitting and prediction is carried out using Markov
      chain Monte Carlo methods. The model primarily facilitates mapping of habitat
      conditions, which is useful in varied monitoring and assessment capacities. More
      importantly, the predictive capability of the model provides a rigorous
      statistical framework for directing management and conservation activities by
      enabling characterization of habitat structure at any point on the landscape.

PMID- 12071400
TI  - Bayesian prediction of spatial count data using generalized linear mixed models.
AB  - Spatial weed count data are modeled and predicted using a generalized linear
      mixed model combined with a Bayesian approach and Markov chain Monte Carlo.
      Informative priors for a data set with sparse sampling are elicited using a
      previously collected data set with extensive sampling. Furthermore, we
      demonstrate that so-called Langevin-Hastings updates are useful for efficient
      simulation of the posterior distributions, and we discuss computational issues
      concerning prediction.

PMID- 12071401
TI  - Modeling spatial survival data using semiparametric frailty models.
AB  - We propose a new class of semiparametric frailty models for spatially correlated
      survival data. Specifically, we extend the ordinary frailty models by allowing
      random effects accommodating spatial correlations to enter into the baseline
      hazard function multiplicatively. We prove identifiability of the models and give
      sufficient regularity conditions. We propose drawing inference based on a
      marginal rank likelihood. No parametric forms of the baseline hazard need to be
      assumed in this semiparametric approach. Monte Carlo simulations and the Laplace
      approach are used to tackle the intractable integral in the likelihood function.
      Different spatial covariance structures are explored in simulations and the
      proposed methods are applied to the East Boston Asthma Study to detect prognostic
      factors leading to childhood asthma.

PMID- 12071402
TI  - Analysis of failure time data with dependent interval censoring.
AB  - This article develops a method for the analysis of screening data for which the
      chance of being screened is dependent on the event of interest (informative
      censoring). Because not all subjects make all screening visits, the data on the
      failure of interest is interval censored. We propose a model that will properly
      adjust for the dependence to obtain an unbiased estimate of the nonparametric
      failure time function, and we provide an extension for applying the method for
      estimation of the regression parameters from a (discrete time) proportional
      hazards regression model. The method is applied on a data set from an
      observational study of cytomegalovirus shedding in a population of HIV-infected
      subjects who participated in a trial conducted by the AIDS Clinical Trials Group.

PMID- 12071403
TI  - Survival analysis with time-varying regression effects using a tree-based
      approach.
AB  - Nonproportional hazards often arise in survival analysis, as is evident in the
      data from the International Non-Hodgkin's Lymphoma Prognostic Factors Project. A
      tree-based method to handle such survival data is developed for the assessment
      and estimation of time-dependent regression effects under a Cox-type model. The
      tree method approximates the time-varying regression effects as piecewise
      constants and is designed to estimate change points in the regression parameters.
      A fast algorithm that relies on maximized score statistics is used in recursive
      segmentation of the time axis. Following the segmentation, a pruning algorithm
      with optimal properties similar to those of classification and regression trees
      (CART) is used to determine a sparse segmentation. Bootstrap resampling is used
      in correcting for overoptimism due to split point optimization. The piecewise
      constant model is often more suitable for clinical interpretation of the
      regression parameters than the more flexible spline models. The utility of the
      algorithm is shown on the lymphoma data, where we further develop the published
      International Risk Index into a time-varying risk index for non-Hodgkin's
      lymphoma.

PMID- 12071404
TI  - Modeling multivariate survival data by a semiparametric random effects
      proportional odds model.
AB  - In this article, the focus is on the analysis of multivariate survival time data
      with various types of dependence structures. Examples of multivariate survival
      data include clustered data and repeated measurements from the same subject, such
      as the interrecurrence times of cancer tumors. A random effect semiparametric
      proportional odds model is proposed as an alternative to the proportional hazards
      model. The distribution of the random effects is assumed to be multivariate
      normal and the random effect is assumed to act additively to the baseline log
      odds function. This class of models, which includes the usual shared random
      effects model, the additive variance components model, and the dynamic random
      effects model as special cases, is highly flexible and is capable of modeling a
      wide range of multivariate survival data. A unified estimation procedure is
      proposed to estimate the regression and dependence parameters simultaneously by
      means of a marginal-likelihood approach. Unlike the fully parametric case, the
      regression parameter estimate is not sensitive to the choice of correlation
      structure of the random effects. The marginal likelihood is approximated by the
      Monte Carlo method. Simulation studies are carried out to investigate the
      performance of the proposed method. The proposed method is applied to two well
      known data sets, including clustered data and recurrent event times data.

PMID- 12071405
TI  - A semiparametric model for the analysis of recurrent-event panel data.
AB  - In many longitudinal studies, interest focuses on the occurrence rate of some
      phenomenon for the subjects in the study. When the phenomenon is nonterminating
      and possibly recurring, the result is a recurrent-event data set. Examples
      include epileptic seizures and recurrent cancers. When the recurring event is
      detectable only by an expensive or invasive examination, only the number of
      events occurring between follow-up times may be available. This article presents
      a semiparametric model for such data, based on a multiplicative intensity model
      paired with a fully flexible nonparametric baseline intensity function. A random
      subject-specific effect is included in the intensity model to account for the
      overdispersion frequently displayed in count data. Estimators are determined from
      quasi-likelihood estimating functions. Because only first- and second-moment
      assumptions are required for quasi-likelihood, the method is more robust than
      those based on the specification of a full parametric likelihood. Consistency of
      the estimators depends only on the assumption of the proportional intensity
      model. The semiparametric estimators are shown to be highly efficient compared
      with the usual parametric estimators. As with semiparametric methods in survival
      analysis, the method provides useful diagnostics for specific parametric models,
      including a quasi-score statistic for testing specific baseline intensity
      functions. The techniques are used to analyze cancer recurrences and a pheromone
      based mating disruption experiment in moths. A simulation study confirms that,
      for many practical situations, the estimators possess appropriate small-sample
      characteristics.

PMID- 12071406
TI  - Analysis of clustered binary outcomes using within-cluster paired resampling.
AB  - Conditional logistic regression (CLR) is useful for analyzing clustered binary
      outcome data when interest lies in estimating a cluster-specific exposure
      parameter while treating the dependency arising from random cluster effects as a
      nuisance. CLR aggregates unmeasured cluster-specific factors into a cluster
      specific baseline risk and is invalid in the presence of unmodeled heterogeneous
      covariate effects or within-cluster dependency. We propose an alternative,
      resampling-based method for analyzing clustered binary outcome data, within
      cluster paired resampling (WCPR), which allows for within-cluster dependency not
      solely due to baseline heterogeneity. For example, dependency may be in part
      caused by heterogeneity in response to an exposure across clusters due to
      unmeasured cofactors. When both CLR and WCPR are valid, our simulations suggest
      that the two methods perform comparably. When CLR is invalid, WCPR continues to
      have good operating characteristics. For illustration, we apply both WCPR and CLR
      to a periodontal data set where there is heterogeneity in response to exposure
      across clusters.

PMID- 12071407
TI  - Marginalized transition models and likelihood inference for longitudinal
      categorical data.
AB  - Marginal generalized linear models are now frequently used for the analysis of
      longitudinal data. Semiparametric inference for marginal models was introduced by
      Liang and Zeger (1986, Biometrics 73, 13-22). This article develops a general
      parametric class of serial dependence models that permits likelihood-based
      marginal regression analysis of binary response data. The methods naturally
      extend the first-order Markov models of Azzalini (1994, Biometrika 81, 767-775)
      and prove computationally feasible for long series.

PMID- 12071408
TI  - Random effects logistic regression analysis with auxiliary covariates.
AB  - We study a semiparametric estimation method for the random effects logistic
      regression when there is auxiliary covariate information about the main exposure
      variable. We extend the semiparametric estimator of Pepe and Fleming (1991,
      Journal of the American Statistical Association 86, 108-113) to the random
      effects model using the best linear unbiased prediction approach of Henderson
      (1975, Biometrics 31, 423-448). The method can be used to handle the missing
      covariate or mismeasured covariate data problems in a variety of real
      applications. Simulation study results show that the proposed method outperforms
      the existing methods. We analyzed a data set from the Collaborative Perinatal
      Project using the proposed method and found that the use of DDT increases the
      risk of preterm births among U.S. children.

PMID- 12071409
TI  - Robust inference for event probabilities with non-Markov event data.
AB  - Multistate event data, in which a single subject is at risk for multiple events,
      is common in biomedical applications. This article considers nonparametric
      estimation of the vector of probabilities of state membership at time t.
      Estimators, derived under the Markov assumption, have been shown (Datta and
      Satten, 2001, Statistics and Probability Letters 55, 403-411) to be consistent
      for data that is non-Markov. Inference, however, must take into account possibly
      non-Markov transitions when constructing confidence bands for event curves. We
      develop robust confidence bands for these curves, evaluate them via simulation,
      and illustrate the method on two datasets.

PMID- 12071410
TI  - Methods for analyzing the spatial distribution of chiasmata during meiosis based
      on recombination data.
AB  - Using genetic recombination data to make inferences about chiasmata on the tetrad
      during meiosis is a classic problem dating back to Weinstein's paper in 1936
      (Genetics 21, 155-199). In the last few years, Weinstein's methods have been
      revived and applied to new problems, but a number of important statistical issues
      remain unresolved. Recently, we developed improved statistical methods for
      studying the frequency distribution of the number of chiasmata (Yu and Feingold,
      2001, Biometrics 57, 427-434). In the current article, we develop methods for the
      complementary issue of studying the spatial distribution of chiasmata. Somewhat
      different statistical approaches are needed for the spatial problem than for the
      frequency problem because different scientific questions are of interest. We
      explore the properties of the maximum likelihood estimate (MLE) for chiasma
      spatial distributions and propose improvements to the estimation procedures. We
      develop a class of statistical tests for comparing chiasma patterns in tetrads
      that have undergone normal meiosis and tetrads that have had a nondisjunction
      event. Finally, we propose an EM algorithm to find the MLE when the observed data
      is ambiguous, as is often the case in human datasets. We apply our improved
      methods to reanalyze a dataset from the literature studying the association
      between crossover location and meiotic nondisjunction of chromosome 21.

PMID- 12071411
TI  - Variable selection in high-dimensional multivariate binary data with application
      to the analysis of microbial community DNA fingerprints.
AB  - In order to understand the relevance of microbial communities on crop
      productivity, the identification and characterization of the rhizosphere soil
      microbial community is necessary. Characteristic profiles of the microbial
      communities are obtained by denaturing gradient gel electrophoresis (DGGE) of
      polymerase chain reaction (PCR) amplified 16S rDNA from soil extracted DNA. These
      characteristic profiles, commonly called community DNA fingerprints, can be
      represented in the form of high-dimensional binary vectors. We address the
      problem of modeling and variable selection in high-dimensional multivariate
      binary data and present an application of our methodology in the context of a
      controlled agricultural experiment.

PMID- 12071412
TI  - A generalized discriminant rule when training population and test population
      differ on their descriptive parameters.
AB  - Standard discriminant analysis methods make the assumption that both the labeled
      sample used to estimate the discriminant rule and the nonlabeled sample on which
      this rule is applied arise from the same population. In this work, we consider
      the case where the two populations are slightly different. In the multinormal
      context, we establish that both populations are linked through linear mapping.
      Estimation of the nonlabeled sample discriminant rule is then obtained by
      estimating parameters of this linear relationship. Several models describing this
      relationship are proposed and associated estimated parameters are given. An
      experimental illustration is also provided in which sex of birds that differ
      morphometrically over their geographical range is to be deterrmined and a
      comparison with the standard allocation rule is performed. Extension to a
      partially labeled sample is also discussed.

PMID- 12071413
TI  - Testing trend for count data with extra-Poisson variability.
AB  - Trend tests for monotone trend or umbrella trend (monotone upward changing to
      monotone downward or vise versa) in count data are proposed when the data exhibit
      extra-Poisson variability. The proposed tests, which are called the GS1 test and
      the GS2 test, are constructed by applying an orthonormal score vector to a
      generalized score test under an rth-order log-linear model. These tests are
      compared by simulation with the Cochran-Armitage test and the quasi-likelihood
      test of Piegorsch and Bailer (1997, Statistics for Environmental Biology and
      Toxicology). It is shown that the Cochran-Armitage test should not be used under
      the existence of extra-Poisson variability; that, for detecting monotone trend,
      the GS1 test is superior to the others; and that the GS2 test has high power to
      detect an umbrella response.

PMID- 12071414
TI  - Age-adjusted exact trend tests in the event of rare occurrences.
AB  - Preclinical animal carcinogenicity studies are usually concerned with testing the
      statistical significance of a dose-response relationship. When the response
      consists of a rare event such as the development of a certain type of tumor,
      exact statistical methods are often employed. The exact randomization trend test
      based on the multivariate hypergeometric distribution is less powerful in the
      presence of treatment-related risks other than the specified response.
      Particularly, the loss of power becomes more pronounced when competing risks
      cause progressively higher mortality rates with increasing dose, which is usual
      in practice. An age-adjusted form of the randomization test is proposed to adjust
      for this effect. Permutational distribution for Peto's cause-of-death (COD) test
      is also explored and compared with its asymptotic counterpart by simulation. The
      use of COD information has been a controversial issue due to the subjectivity in
      the pathologists' determinations as well as for economic reasons. The proposed
      age-adjusted exact test does not require COD, and it is shown to compare
      favorably to the COD tests via an extensive Monte Carlo simulation. Applications
      of the methods to two real data sets are included.

PMID- 12071415
TI  - A semiparametric empirical likelihood method for data from an outcome-dependent
      sampling scheme with a continuous outcome.
AB  - Outcome-dependent sampling (ODS) schemes can be a cost effective way to enhance
      study efficiency. The case-control design has been widely used in epidemiologic
      studies. However, when the outcome is measured on a continuous scale,
      dichotomizing the outcome could lead to a loss of efficiency. Recent
      epidemiologic studies have used ODS sampling schemes where, in addition to an
      overall random sample, there are also a number of supplemental samples that are
      collected based on a continuous outcome variable. We consider a semiparametric
      empirical likelihood inference procedure in which the underlying distribution of
      covariates is treated as a nuisance parameter and is left unspecified. The
      proposed estimator has asymptotic normality properties. The likelihood ratio
      statistic using the semiparametric empirical likelihood function has Wilks-type
      properties in that, under the null, it follows a chi-square distribution
      asymptotically and is independent of the nuisance parameters. Our simulation
      results indicate that, for data obtained using an ODS design, the semiparametric
      empirical likelihood estimator is more efficient than conditional likelihood and
      probability weighted pseudolikelihood estimators and that ODS designs (along with
      the proposed estimator) can produce more efficient estimates than simple random
      sample designs of the same size. We apply the proposed method to analyze a data
      set from the Collaborative Perinatal Project (CPP), an ongoing environmental
      epidemiologic study, to assess the relationship between maternal polychlorinated
      biphenyl (PCB) level and children's IQ test performance.

PMID- 12071416
TI  - A general approach to confidence regions for optimal factor levels of response
      surfaces.
AB  - For a response surface experiment, an approximate hypothesis test and an
      associated confidence region is proposed for the minimizing (or maximizing)
      factor-level configuration. Carter et al. (1982, Cancer Research 42, 2963-2971)
      show that confidence regions for optimal conditions provide a way to make
      decisions about therapeutic synergism. The response surface may be constrained to
      be within a specified, bounded region. These constraint regions can be quite
      general. This allows for more realistic constraint modeling and a wide degree of
      applicability, including constraints occurring in mixture experiments. The usual
      assumption of a quadratic model is also generalized to include any regression
      model that is linear in the model parameters. An intimate connection is
      established between this confidence region and the Box-Hunter (1954, Biometrika
      41, 190-199) confidence region for a stationary point. As a byproduct, this
      methodology also provides a way to construct a confidence interval for the
      difference between the optimal mean response and the mean response at a specified
      factor-level configuration. The application of this confidence region is
      illustrated with two examples. Extensive simulations indicate that this
      confidence region has good coverage properties.

PMID- 12071418
TI  - A modification of Peto's nonparametric estimation of survival curves for interval
      censored data.
AB  - Peto (1973, Applied Statistics, 22, 86-91) gave a nonparametric generalized
      maximum-likelihood estimate of the survival function for interval-censored data.
      His method has a tendency to concentrate probability masses at the endpoints of
      the intervals, even for the ordinary grouped data, instead of spreading them
      through the intervals, as one might expect them to be in the underlying
      distribution. We describe a modification that overcomes this. The new estimate
      reduces to the standard binomial estimate when applied to grouped data. It also
      reduces to the Kaplan-Meier estimate when applied to survival data that consist
      of only exact or right-censored observations. Both estimates are maximum
      likelihood estimates but are based on different interpretations of the endpoints
      of the intervals.

PMID- 12071417
TI  - Self-designing two-stage trials to minimize expected costs.
AB  - In the design of clinical trials, the sample size for the trial is traditionally
      calculated from estimates of parameters of interest, such as the mean treatment
      effect, which can often be inaccurate. However, recalculation of the sample size
      based on an estimate of the parameter of interest that uses accumulating data
      from the trial can lead to inflation of the overall Type I error rate of the
      trial. The self-designing method of Fisher, also known as the variance-spending
      method, allows the use of all accumulating data in a sequential trial (including
      the estimated treatment effect) in determining the sample size for the next stage
      of the trial without inflating the Type I error rate. We propose a self-designing
      group sequential procedure to minimize the expected total cost of a trial. Cost
      is an important parameter to consider in the statistical design of clinical
      trials due to limited financial resources. Using Bayesian decision theory on the
      accumulating data, the design specifies sequentially the optimal sample size and
      proportion of the test statistic's variance needed for each stage of a trial to
      minimize the expected cost of the trial. The optimality is with respect to a
      prior distribution on the parameter of interest. Results are presented for a
      simple two-stage trial. This method can extend to nonmonetary costs, such as
      ethical costs or quality-adjusted life years.

PMID- 12071419
TI  - Generalized additive models with interval-censored data and time-varying
      covariates: application to human immunodeficiency virus infection in
      hemophiliacs.
AB  - We describe a method for extending smooth nonparametric modeling methods to time
      to-event data where the event may be known only to lie within a window of time.
      Maximum penalized likelihood is used to fit a discrete proportional hazards model
      that also models the baseline hazard, and left-truncation and time-varying
      covariates are accommodated. The implementation follows generalized additive
      modeling conventions, allowing both parametric and smooth terms and specifying
      the amount of smoothness in terms of the effective degrees of freedom. We
      illustrate the method on a well-known interval-censored data set on time of human
      immunodeficiency virus infection in a multicenter study of hemophiliacs. The
      ability to examine time-varying covariates, not available with previous methods,
      allows detection and modeling of nonproportional hazards and use of a time
      varying covariate that fits the data better and is more plausible than a fixed
      alternative.

PMID- 12071420
TI  - Semiparametric maximum likelihood for nonlinear regression with measurement
      errors.
AB  - This article demonstrates semiparametric maximum likelihood estimation of a
      nonlinear growth model for fish lengths using imprecisely measured ages. Data on
      the species corvina reina, found in the Gulf of Nicoya, Costa Rica, consist of
      lengths and imprecise ages for 168 fish and precise ages for a subset of 16 fish.
      The statistical problem may therefore be classified as nonlinear errors-in
      variables regression with internal validation data. Inferential techniques are
      based on ideas extracted from several previous works on semiparametric maximum
      likelihood for errors-in-variables problems. The illustration of the example
      clarifies practical aspects of the associated computational, inferential, and
      data analytic techniques.

PMID- 12071421
TI  - A simple Bayesian analysis of misclassified binary data with a validation
      substudy.
AB  - A two-stage Bayesian method is presented for analyzing case-control studies in
      which a binary variable is sometimes measured with error but the correct values
      of the variable are known for a random subset of the study group. The first stage
      of the method is analytically tractable and MCMC methods are used for the second
      stage. The posterior distribution from the first stage becomes the prior
      distribution for the second stage, thus transferring all relevant information
      between the stages. The method makes few distributional assumptions and requires
      no asymptotic approximations. It is computationally fast and can be run using
      standard software. It is applied to two data sets that have been analyzed by
      other methods, and results are compared.

PMID- 12071422
TI  - Determination of the unknown age at first capture of western rock lobsters
      (Panulirus cygnus) by random effects model.
AB  - We propose a method for fitting growth curves to multiple recapture data of
      lobsters when the age at first capture is unknown. The von Bertalanffy growth
      curve is used to model the growth. To account for individual variability, the
      unknown age in logarithmic scale of a lobster at first capture, the individual
      asymptotic size, and the individual growth coefficient of its carapace length are
      modeled as random effects with a trivariate normal distribution. Unlike
      previously suggested models, the present model permits correlation between the
      growth coefficient and the age at first capture and can be fitted readily using
      existing software. The error structures between consecutive recaptures of a
      lobster are assumed to be a first-order autoregressive process with unequally
      spaced time points. A comparison between this model and the Fabens growth
      equation is given. The proposed method is a flexible method and can be applied to
      fit different growth equations when the age at first capture is unknown.

PMID- 12071423
TI  - Likelihood analysis for the ratio of means of two independent log-normal
      distributions.
AB  - Existing methods for comparing the means of two independent skewed log-normal
      distributions do not perform well in a range of small-sample settings such as a
      small-sample bioavailability study. In this article, we propose two likelihood
      based approaches-the signed log-likelihood ratio statistic and modified signed
      log-likelihood ratio statistic-for inference about the ratio of means of two
      independent log-normal distributions. More specifically, we focus on obtaining p
      values for testing the equality of means and also constructing confidence
      intervals for the ratio of means. The performance of the proposed methods is
      assessed through simulation studies that show that the modified signed log
      likelihood ratio statistic is nearly an exact approach even for very small
      samples. The methods are also applied to two real-life examples.

PMID- 12071424
TI  - An application of population kinetics analysis to estimate pharmacokinetic
      parameters of sodium tungstate after multiple-dose during preclinical studies in
      rats.
AB  - The purpose of this study was to use a population approach in the preclinical
      development program of sodium tungstate in the rat in order i) to compute
      individual pharmacokinetic parameters of this compound after repeated oral
      administrations, until the 4-week toxicology study, using an empirical Bayes
      methodology; and ii) to study the influence of the administered dose, of the
      gender and of the duration of treatment on the pharmacokinetic parameters. Four
      studies were used representing a mixture of single intravenous administration and
      multiple oral administrations. The treatment duration ranged from 7 to 28 days.
      Intravenous dose was 9 mg/kg; three different oral doses were tested, 50, 100 and
      200 mg/kg/day. Plasma concentration profiles versus time were compatible with a
      two-compartment model. A significant gender effect was found on bioavailability.
      The duration of treatment and the administered dose did not significantly explain
      part of the interindividual variability of pharmacokinetic parameters. The
      absorption of tungsten was rapid (1-3 hr). Total plasma clearance and elimination
      half-life averaged 2.8 ml/min/kg and 3.04 hr in males, and 3 ml/min/kg and 2.74
      hr in females. The bioavailability was on an average 70%; being significantly
      higher in females than in males (0.78 versus 0.61). This compartmental approach
      should be considered as complementary to the usual non-compartmental approach
      used for analysis of preclinical data and should be a valuable tool to
      characterise the pharacokinetic/pharmacodynamic behaviour of a drug.

PMID- 12071425
TI  - Phyllodulcin, a constituent of "Amacha", inhibits phosphodiesterase in bovine
      adrenocortical cells.

PMID- 12071426
TI  - Modulation of fluoride toxicity in rats by calcium carbonate and by withdrawal of
      fluoride exposure.
AB  - In order to assess the effect of calcium on the toxic effects of fluoride, adult
      female Wistar rats were treated with sodium fluoride (NaF, 500 ppm in drinking
      water) alone or in combination with calcium carbonate (CaCO3, 50 mg/ kg by oral
      intubation) daily for 60 days. Food, water and fluoride intake were measured
      daily for 60 days. Body weight gain, exploratory motor activity, rota-rod motor
      coordination, dental structure, activities of acetylcholinesterase (AchE, brain
      and skeletal muscle) and Na+ K+ ATPase (erythrocyte membrane and skeletal muscle)
      and the concentrations of protein (serum and skeletal muscle), calcium (serum)
      and fluoride (serum) were determined in these animals 24 hr after the last
      treatment. The same parameters were tested in another group, 60 days after
      withdrawal of NaF exposure (500 ppm in drinking water daily for 60 days). NaF
      treatment decreased food and water intake, reduced body-weight gain and impaired
      exploratory motor activity and rota-rod performance. Dental lesions, inhibition
      of the activities of AchE and N+ K+ ATPase and a decrease in the concentration of
      protein, and serum calcium were also observed in these animals. These effects
      were accompanied by a marked elevation of fluoride concentration in the serum.
      CaCO3 decreased the concentration of fluoride in the serum of NaF-treated
      animals. A decrease in serum fluoride concentration was found also after NaF
      withdrawal. A prevention of locomotor behavioural, biochemical and dental
      toxicities of fluoride was observed both in these groups. It is concluded that
      the dose of CaCO3 used in the present study has a potential to prevent the
      toxicity of fluoride by maintaining serum fluoride at a less toxic level.
      Further, the toxic effects of fluoride are reversible if its exposure is
      withdrawn for 2 months.

PMID- 12071427
TI  - In utero exposure to diethylstilboestrol or 4-n-nonylphenol in rats: number of
      sertoli cells, diameter and length of seminiferous tubules estimated by
      stereological methods.
AB  - The effects on testis weight and histopathology were studied in 11-day-old male
      Wistar rats after prenatal exposure to peanut oil (control), diethylstilboestrol
      30 microg/kg b.wt./day, or 4-n-nonylphenol 75 mg/kg b.wt./day from gestational
      day 11 to 18. Additionally, the diameter and length of seminiferous tubules, and
      the number of Sertoli cells were investigated with stereological methods. Such
      unbiased methods have not previously been applied on testis diameter and length
      or on Sertoli cell number of 11-day-old rats. In the control group, the mean
      length of the seminiferous tubule was 3.0 m+/-0.6, the mean diameter of the
      seminiferous tubule was 83 microm+/-6, and the mean number of Sertoli cells was
      26.1x10(6)+/-4.6. No differences in testis weight, histopathology, or length or
      diameter of the seminiferous tubules were observed in the diethylstilboestrol and
      nonylphenol exposed groups when compared to the control group. In the
      diethylstilboestrol-treated group, a statistically significant decrease in the
      number of Sertoli cells was observed (P<0.01) when compared to the control group,
      whereas nonylphenol had no effect. The result suggests that diethylstilboestrol
      decreases Sertoli cell proliferation in the foetal testis and furthermore
      indicate that oestrogens may pose a risk to the reproductive capacity in
      sensitive species, including man.

PMID- 12071429
TI  - Effects of rhIGF-I and insulin-induced hypoglycaemia on cardiovascular parameters
      recorded with telemetry in the conscious dog.
AB  - Using telemetry, the effects on cardiovascular parameters after single
      intravenous administration (0.5 mg/kg) of recombinant human insulin-like growth
      factor-I (rhIGF-I) were studied in conscious and unrestrained dogs. Insulin (1.1
      IU/kg) was used as a reference compound. Telemetry transmitters were implanted
      subcutaneously with a pressure catheter in the femoral artery and electrodes for
      ECG subcutaneously. Cardiovascular effects and changes in blood glucose levels
      induced with rhlGF-I were similar to those induced with insulin. Heart rate
      increased continuously for about 90 min. after treatment, regardless of compound.
      Thereafter, heart rate slowly decreased but did not fully reach predose values 4
      hr after treatment. Both systolic and diastolic blood pressure decreased
      continuously for about 90 min. and remained low for up to 4 hr after treatment.
      Treatment with rhIGF-I or insulin did not influence dp/dt values. Treatment with
      glucose intravenously to abolish the rhIGF-I-induced hypoglycaemia reduced the
      heart rate, but caused a substantial increase in dp/dt and a slight increase in
      blood pressure. RhIGF-I and insulin induced an almost identical onset and degree
      of hypoglycaemia. Blood glucose reached a minimum level 1 hr after treatment and
      was almost returned to normal 4 hr after treatment. There was an increase in the
      amplitude of the T-waves, though this effect occurred earlier and was longer
      lasting with insulin than with rhIGF-I. After 4 hr, the T-wave amplitude was
      normal with rhIGF-I but remained high with insulin. These T-wave effects were
      probably due to an increase in the transport of potassium or calcium since they
      decreased in plasma. This suggests that the effects of rhIGF-I and insulin are
      highly comparable and that the cardiovascular changes induced by rhIGF-I are
      likely caused by its insulin-like activity. As shown by the recorded
      cardiovascular responses induced by rhIGF-1 and insulin, the telemetric recording
      system makes it possible to evaluate the effects of different drugs in a
      continuous way that is not possible with conventional techniques. This new
      telemetric technique can be of significant importance in the process of future
      drug development.

PMID- 12071428
TI  - Inactivation of creatine kinase induced by stilbene derivatives.
AB  - Compounds acting as antioxidants to lipids often have a prooxidant effect on DNA
      or protein. In this study, inactivation of creatine kinase was examined as an
      indicator of protein damage induced by antioxidative stilbene derivatives,
      including diethylstilboestrol, resveratrol and tamoxifen, with horseradish
      peroxidase and hydrogen peroxide (horseradish peroxidase-H2O2).
      Diethylstilboestrol and resveratrol, but not tamoxifen, rapidly inactivated
      creatine kinase. Also, creatine kinase in heart homogenate was inactivated by
      diethylstilboestrol and resveratrol. Tamoxifen, which has no phenolic hydroxyl
      groups in its structure, was about 10 times less active in protecting lipids and
      creatine kinase than diethylstilboestrol and resveratrol, suggesting that
      phenolic hydroxyl groups in diethylstilboestrol and resveratrol of stilbene
      derivatives are anti- and pro-oxidative. Absorption spectra of these stilbene
      derivatives rapidly changed during the reaction with horseradish peroxidase-H202.
      Diethylstilboestrol and resveratrol free radicals emitted electron spin resonance
      signals and creatine kinase effectively diminished the electron spin resonance
      signals. These results suggest that free radicals of diethylstilboestrol and
      resveratrol formed through reaction with horseradish peroxidase-H202 inactivated
      creatine kinase. Presumably, oxidation of essential cysteine and tryptophan
      residues lead to inactivation of creatine kinase. Other enzymes, including
      alcohol dehydrogenase and cholinesterase, were also sharply inhibited by
      diethylstilboestrol and resveratrol with horseradish peroxidase-H202. Free
      radicals of diethylstilboestrol and resveratrol seem to mediate between anti- and
      prooxidative actions.

PMID- 12071430
TI  - Evaluation of dextromethorphan N-demethylation activity as a biomarker for
      cytochrome P450 3A activity in man.
AB  - The present study evaluates the usefulness of dextromethorphan N-demethylation
      activity indices to reflect cytochrome P450 (CYP) 3A activity in man. Indices of
      dextromethorphan N-demethylation activity were categorized as N1=3
      methoxymorphinan/dextromethorphan, N2=3-hydroxymorphinan/dextrorphan, N3=(3
      methoxymorphinan + 3-hydroxymorphinan)/(dextromethorphan + dextrorphan). Two mg
      of midazolam were administered orally to 22 Japanese male volunteers, and
      midazolam clearance determined. Thirty mg of dextromethorphan were also orally
      administered to these volunteers and N1, N2 and N3 indices determined by 12 hr
      urine collection. Results showed N2 and N3 were highly correlated (r>0.99,
      P<0.001), and significantly correlated to oral midazolam clearance (r=0.45,
      P<0.05); suggesting that N2 and N3 are more suitable than N, when using
      dextromethorphan as an index of individual CYP3A activity.

PMID- 12071431
TI  - Lithium inhibits the development of physical dependence to clonidine in mice.
AB  - Based on our previous finding that chronic lithium treatment reduced naloxone
      precipitated withdrawal syndrome in morphine-treated mice, the effect of chronic
      lithium treatment was evaluated on the development of dependence to clonidine.
      Dependence was induced by injection of either morphine (50, 50 and 75 mg/kg,
      intraperitoneally with 3 hr interval for 3 consecutive days), or clonidine (2
      mg/kg/day, intraperitoneally for 10 days). Naloxone (4 mg/kg, intraperitoneally)
      precipitated withdrawal signs in both morphine- and clonidine-treated mice.
      Yohimbine (5 mg/kg, intraperitoneally) precipitated withdrawal signs in the
      clonidine-treated mice, similar to morphine withdrawal signs; but failed to
      precipitate any significant sign in the morphine-treated mice. Coadministration
      of lithium was carried out by adding lithium chloride to drinking water (600 mg/l
      for 20 days; 10 days before the beginning of clonidine administration and 17 days
      before the administration of morphine to allow the lithium concentration to reach
      steady-state). The results indicated that chronic lithium administration
      significantly attenuated the withdrawal signs, precipitated either by yohimbine
      or naloxone, in clonidine-treated mice. As a conclusion, clonidine withdrawal
      signs are very similar to opioid withdrawal signs, and lithium is able to prevent
      the development of physical dependence to clonidine.

PMID- 12071432
TI  - Blockade of spinal dopamine D2 receptors enhances the pressor effect of
      intravenous quinpirole in normotensive, conscious rats.
AB  - The present investigation was undertaken to examine whether in conscious intact
      rats blockade of spinal dopamine D2 receptors enhances the pressor effect of
      intravenous quinpirole. In saline-pretreated rats, intravenous quinpirole (1
      mg/kg) induced a significant pressor effect, which reached a maximum (17.71+/
      0.60 mmHg) within the first min. after injection. Pretreatment with intravenous
      (0.5 mg/kg) or intrathecal (40 microg/rat at T9-T10) domperidone, a dopamine D2
      receptor antagonist that does not cross the blood-brain barrier, significantly
      enhanced the maximal pressor response to quinpirole (25.60+/-1.52 and 24.00+/
      1.72 mmHg, respectively). The pressor effect of quinpirole was also significantly
      enhanced after combined pretreatment with intravenous and intrathecal
      domperidone, and its maximum (31.60+/-2.31 mmHg) was significantly higher than
      that recorded in animals pretreated with intrathecal or intravenous domperidone
      alone. Intravenous pretreatment with metoclopramide (5 mg/kg) fully abolished the
      quinpirole-induced pressor effect. These results show that in conscious intact
      rats, blockade of spinal dopamine D2 receptors enhances the pressor response to
      systemic quinpirole, suggesting that this agonist can decrease blood pressure
      through a spinal dopaminergic mechanism. Thus, our previous hypothesis that the
      entire effect of intravenous quinpirole on blood pressure in conscious rats can
      be composed of a central pressor action, a peripheral sympathoinhibitory
      depressor effect and also a spinal depressor effect is strongly supported by the
      present findings.

PMID- 12071433
TI  - Genetic immunization maps T cell (auto)immune responses to self antigens
      homologous to exogenous proteins.
AB  - Genetic immunization represents a new tool for investigating physiological and
      pathological immune responses. Here we used genetic immunization with naked DNA
      to study the immune relevance of aminoacid sequence homologies by evaluating the
      outcome of immunization to a viral protein homologous to an HLA molecule. The
      viral protein was Balf2, a protein of Epstein-Barr virus (EBV) that shares
      aminoacid sequence homology with the HLA allele DRB1*0801. After genetic
      immunization of BALB/c mice with a construct encoding Balf2, we analyzed T cell
      responses of immunized mice. We found that cross-reactive proliferative and
      cytotoxic responses were raised to the homologous sequence as expressed by HLA
      DRB1*0801. Furthermore, preferential secretion of Th1-type pro-inflammatory
      cytokines occurred. This strategy can allow rapid screening of interactive immune
      networks involving aminoacid sequence homologies between organisms.

PMID- 12071434
TI  - Autologous mixed lymphocyte responses in experimentally-induced arthritis of the
      Lewis rat.
AB  - Lewis rats develop immune-mediated arthritis following injection with a variety
      of agents including bovine type II collagen (bCII), mycobacteria, muramyl
      dipeptide and CP20961. Since susceptibility to experimentally-induced arthritis
      has been linked to the genes encoding the major histocompatibility complex, it is
      hypothesized that antigen presentation to autoreactive T-cells is a critical
      event in the pathogenesis of disease. T-cells, isolated from Lewis rats immunized
      with bCII or mycobacteria, were co-cultured with splenic or thymic antigen
      presenting cells (APC) and proliferative responses to antigen were assessed by 3H
      thymidine incorporation. T-cell proliferation was observed upon culture with APC
      without requiring the addition of antigen. T-cells from rats injected with non
      immunogenic adjuvants also demonstrated an increased autologous MLR compared to T
      cells from non-injected animals. In contrast, T-cells from animals immunized with
      non-arthritogenic antigens, including ovalbumin or tetanus toxoid, proliferated
      only when co-cultured with specific antigen-pulsed APC. These results suggest
      that immunization with arthritogens activates a population of self-reactive T
      cells, which respond in an autologous MLR. We propose that these autoreactive T
      cells recognize endogenously-derived self peptides rather than peptides derived
      from a joint autoantigen.

PMID- 12071435
TI  - Construction and characterization of a single-chain antibody fragment derived
      from thymus of a patient with myasthenia gravis.
AB  - Pathogenic anti-acetylcholine receptor (AChR) antibodies in myasthenia gravis
      (MG) and the corresponding animal model, experimental autoimmune myasthenia
      gravis (EAMG), principally recognize the main immunogenic region (MIR) of the
      AChR. Bivalent anti-MIR antibodies binding to the alpha-subunits of AChR result
      in AChR loss by antigenic modulation and complement activation. Monovalent Fab
      and single-chain variable fragments (scFv) of pathogenic anti-AChR antibodies can
      interfere with AChR binding of the pathogenic antibodies. In the present study,
      scFv637 was constructed from its parental Fab637, previously isolated from a
      thymus-derived phage display library with specificity toward anti-MIR of human
      AChR (hAChR), by PCR amplification. Bacterial produced scFv637 was able to bind
      to hAChR in standard precipitation radioimmunoassay (RIA). ScFv637 also bound to
      monkey AChR in situ on monkey neuromuscular junctions as showed in
      immunohistochemical staining. Furthermore, scFv637 was capable of inhibiting the
      binding of its intact IgG637 and anti-MIR mAb35 binding to hAChR up to 32.9 and
      73.0%, respectively demonstrated in a competitive ELISA, and of MG patient sera
      from up to 45.5% in a competitive RIA. Therefore, scFv637, easier for
      manipulation in improvement of affinity and stability compared with its parental
      Fab637, may serve as an alternative candidate for specific immunotherapy in MG.

PMID- 12071436
TI  - Clinical significance of positive immunoblotting but negative immunofluorescence
      for antimitochondrial antibodies in patients with liver diseases other than
      primary biliary cirrhosis.
AB  - The serum reaction to anti-2-oxo-acid dehydrogenase complex (2-OADC) enzymes, the
      antigens recognized by antimitochondrial antibodies (AMA), can be detected by
      immunoblotting in patients with liver diseases other than primary biliary
      cirrhosis (PBC), who are negative for AMA by conventional indirect
      immunofluorescence. Whether the presence of anti-2-OADC is related to PBC or
      represents preclinical PBC in such patients is obscure at present. We examined
      the immunoreactivity of AMA by immunofluorescense, immunoblotting, and enzyme
      inhibition assay in serum samples from 59 patients with liver diseases other than
      PBC and 71 healthy subjects. We also examined the clinical course of the patients
      in whom a positive result was obtained to elucidate whether such reaction was a
      "true" or "false" phenomenon. None of the 130 sera was positive for AMA by
      indirect immunofluorescence or for anti-pyruvate dehydrogenase complex (PDC) by
      enzyme inhibition assay. However, seven of 71 (10%) sera from healthy subjects
      contained weak IgG class antibody to PDC-E2 (four sera) or E2 subunit of branched
      chain oxo-acid dehydrogenase complex (BCOADC-E2) (three sera). Of the 59 sera
      from patients with liver diseases other than PBC, four (7%) reacted against 2
      OADC by immunoblotting. Of these, three sera were from patients with chronic
      hepatitis C virus (HCV) infection, and contained IgG class autoantibody to BCOADC
      E2. The serum reactivity to BCOADC-E2 detected by immunoblotting in these three
      patients diminished after absorption with recombinant BCOADC-E2 fusion protein.
      During the 3-5 year follow-up period, AMA by immunofluorescence and anti-PDC
      activity by enzyme inhibition assay were always negative in these three patients.
      The other one serum was from patient with alcoholic cirrhosis, and contained IgM
      class autoantibody to E3 binding protein (E3-BP). This patient did not develop
      PBC during the following 2 years. Our results showed that anti-2-OADC antibodies
      could be detected in some patients with liver diseases other than PBC, and even
      in healthy individuals. The clinical significance of the presence of these serum
      reactions is obscure at this stage, but the production of anti-BCOADC-E2 may be
      linked to the presence of HCV in certain patients. Further prospective studies of
      larger population should clarify whether anti-2-OADC reaction can precede the
      clinical development of PBC.

PMID- 12071437
TI  - Prophylactic insulin treatment of diabetes-prone BB/OK rats by application of a
      sustained release insulin implant.
AB  - Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to
      prophylactic insulin treatment by means of a single subcutaneous application of a
      sustained release insulin implant. The single application of a sustained release
      insulin implant decreased the incidence of diabetes or delayed the onset of the
      disease in BB/OK rats of all treatment groups. Prophylactic insulin
      administration caused a transient hypoglycemic period accompanied by an
      inhibition of glucose stimulated insulin secretion and a decrease of the insulin
      content of Langerhans' islets as detectable in vitro. Compared to islets of
      normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats
      within 7-21 days after the insulin application at 45 days of age displayed a
      decreased susceptibility of the cells to complement-dependent cytotoxicity of the
      monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic
      effect of the ICSA M3aG8. The appearance of complement-dependent antibody
      mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum
      regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected
      by insulin prophylaxis and was detectable during hypoglycemia as well as in the
      subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be
      protected from diabetes by a single application of a sustained release insulin
      implant. Insulin and/or hypoglycemia seem to influence the expression of cell
      surface antigens, thus render the islets of Langerhans less vulnerable to immune
      cytolysis, whereas the appearance of humoral immunological abnormalites is not
      affected.

PMID- 12071438
TI  - Sequencing of the second exon of the MHC class II DQ6 alleles in patients with
      type 1 diabetes.
AB  - The MHC class II molecule DQ6 is strongly associated with protection from type 1
      diabetes. A small number of diabetic subjects have been typed as positive for
      DQ6, but it has been suggested that these individuals may possess a mutant form
      of the molecule, which is structurally altered in such a way as to abrogate its
      protective effect. In order to test this hypothesis, eight diabetic individuals
      positive for DQ6 were investigated. The second exons of the alleles encoding DQ6,
      DQA1*0102 and DQB1*0602, were sequenced using fluorescently labelled
      dideoxynucleotides. No mutations were found. This suggests that all the subjects
      possessed the "wild-type" second exons of the DQ6 alleles and, hence, that the
      protective effect associated with the antigen-binding domain of DQ6 is not
      absolute.

PMID- 12071439
TI  - Autoantibodies in neuropsychiatric lupus.
AB  - The American College of Rheumatology presented a consensus document in 1999
      proposing the classification of 19 different syndromes defined by neurological
      and psychiatric manifestations of systemic lupus erythematosus (SLE). The
      detection of autoantibodies in patient's serum or cerebrospinal fluid has not
      been used as diagnostic markers for the proposed neuropsychiatric lupus
      classifications as their disease associations remain highly contentious.
      Autoantibodies detected in the serum and/or cerebrospinal fluid, that have been
      reported to segregate with patients presenting with neuropsychiatric lupus
      include: (1) anti-neuronal antibodies, (2) brain-lymphocyte cross-reactive
      antibodies, (3) anti-ribosomal P antibodies, (4) anti-phospholipid antibodies and
      (5) anti-ganglioside antibodies. Tests for anti-neuronal, anti-brain-lymphocyte
      cross-reactive and anti-ganglioside antibodies remain highly specialized whereas
      tests for ribosomal P antibodies and for antiphospholipid antibodies are
      currently routinely available in most diagnostic laboratories. Anti-ribosomal
      antibodies segregate with SLE. Antiphospholipid P antibodies are markers for the
      antiphospholipid syndrome. This syndrome may be associated with another disease,
      commonly SLE. In this setting, neuropsychiatric manifestations in SLE may arise
      as a consequence of thrombotic episodes involving the cerebral vasculature. There
      is a pressing need for antibodies to ribosomal P and to phospholipids to be
      standardized for routine diagnostic application. We conclude that the search for
      specific antibody marker(s) that can be applied for the routine laboratory
      diagnosis for neuropsychiatric lupus remains elusive.

PMID- 12071440
TI  - Production of non-pathogenic human monoclonal antibodies to desmoglein 3 from
      pemphigus vulgaris patient.
AB  - Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous disease
      associated with production of IgG autoantibodies to desmoglein 3, a 130 kDa
      epidermal protein. To further characterize the epitope(s) of pemphigus vulgaris
      antigen we established two human-human hybridoma by fusion of the peripheral
      blood mononuclear cells with a human and mouse heterohybridoma. These hybridomas
      designated as MAb Dsg-3: 06 and MAb Dsg-3: 10 and stable in culture and
      demonstrated yield of monoclonal antibodies specific for pemphigus vulgaris.
      Immunofluorescence, immunoblot, ELISA assays demonstrated that both the
      monoclonal antibodies bind to the intercellular cement substance and to 130 kDa
      protein present in the skin and specifically binds to recombinant desmoglein 3
      protein, but not to desmoglein 1 protein. The IgG subclass distribution study
      demonstrated that both the antibodies are of IgG1 subclass in nature. Both the
      antibodies were non-pathogenic as demonstrated in vitro by their inability to
      produce acantholysis in normal human skin in organ culture or in vivo by the
      induction of disease in neonatal BALB/c mice. The relevance and value of these
      monoclonal antibodies in the pathogenesis of pemphigus vulgaris is discussed.

PMID- 12071441
TI  - Antibodies to blood group antigens mimic pemphigus staining patterns: a useful
      reminder.
AB  - Pemphigus is a clinically important autoimmune skin disease characterised by
      intercellular substance antibodies, detected by indirect immunofluorescence on
      monkey oesphagus tissue. It has been observed that anti-A and anti-B blood group
      antibodies can produce staining patterns similar to that seen in pemphigus, yet
      this potential problem is not well recognised. We have demonstrated false
      positive pemphigus staining with blood group O sera and describe features by
      fluorescence and confocal microscopy, which may be useful in distinguishing true
      from false positive pemphigus staining.

PMID- 12071442
TI  - Levels of MCP-1 and GM-CSF mRNA correlated with inflammatory cytokines mRNA
      levels in experimental autoimmune myocarditis in rats.
AB  - Infiltration of monocytes and T cells is known to be an essential trigger for the
      progression of experimental autoimmune myocarditis (EAM) in rats. Monocyte
      chemotactic protein-1 (MCP-1) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) were shown to mediate the migration of monocytes and T cells into
      inflammatory sites and to proliferate monocytes. Thus, we evaluated levels of MCP
      1 and GM-CSF mRNA in the myocardium of EAM in rats using a real time quantitative
      PCR method. We also examined the correlation of MCP-1 or GM-CSF mRNA levels with
      those of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) in the same lesion. Levels
      of MCP-1, GM-CSF, TNF-alpha, IL-1beta and IL-6 mRNA increased with the
      progression of myocarditis which was accompanied by the accumulation of ED-1
      positive cells. The MCP-1 and GM-CSF mRNA levels were positively correlated with
      TNF-alpha, IL-1beta and IL-6 mRNA levels in the same lesion of EAM. We also
      demonstrated that serum MCP-1 concentrations were increased during the active
      stage of EAM, and were correlated with MCP-1 mRNA levels in the myocardium of
      each rat. These findings suggest that elevated MCP-1 and GM-CSF may associate
      with the migration and proliferation of monocytes/macrophages in EAM. Thus, MCP-1
      and GM-CSF may play an important role in the progression of EAM.

PMID- 12071443
TI  - Complications of biliary T-tubes.

PMID- 12071444
TI  - Primary hyperparathyroidism is a surgical condition.

PMID- 12071445
TI  - Assessment of myocardial injury by troponin T in off-pump coronary artery
      grafting and conventional coronary artery graft surgery.

PMID- 12071446
TI  - Poisons and handwork: interactions between surgeons and medical oncologists.

PMID- 12071447
TI  - Complications of biliary T-tubes after choledochotomy.
AB  - BACKGROUND: Traditional management of choledocholithiasis has been supraduodenal
      choledochotomy, duct exploration and insertion of a T-tube. This study reviews
      the complications associated with T-tube use and assesses whether laparoscopic
      procedures are associated with an increase in complications relating to T-tube
      use. METHODS: Case records from two large public hospitals in New South Wales
      (Australia) were analysed retrospectively for a 10-year period using a
      standardized data collection form. Morbidity, mortality and potential factors
      influencing the complication rate after choledochotomy and T-tube insertion were
      recorded. All complications were reviewed by an experienced biliary surgeon.
      RESULTS: T-tubes were inserted in 274 patients, with 42 patients (15.3%)
      experiencing a total of 60 complications relating to T-tube use. Morbidity
      occurring while the tube was in situ included fluid and electrolyte disturbance
      (five patients), sepsis (10 patients), premature dislodgement (three patients)
      and bile leakage (six patients). Complications resulting after planned tube
      removal included localized pain (13 patients), biliary peritonitis (seven
      patients), a prolonged biliary fistula (seven patients) and a late bile duct
      stricture (one patient). T-tube complications resulted in a prolonged hospital
      stay (19 days vs 13 days, P = 0.005), 10 additional abdominal operations and two
      deaths. Complications related to T-tubes were constant over the study period and
      were similar between laparoscopic and open cases (13.8% vs 15.5%, P = 0.81).
      CONCLUSIONS: Although this retrospective review is likely to have underestimated
      the incidence of T-tube complications, it has demonstrated significant morbidity
      associated with T-tube use. The incidence of these complications has been
      constant and is unrelated to a laparoscopic approach.

PMID- 12071448
TI  - Pattern of management of common bile duct stones in the laparoscopic era: a NSW
      survey.
AB  - BACKGROUND: The management of common bile duct (CBD) stones in the laparoscopic
      era remains controversial with various management strategies employed by
      surgeons. The aim of this study was to ascertain the common practice across a
      single Australian state, and to see if a 'best practice' for CBD stone management
      could be established. METHODS: A questionnaire was sent to 390 general surgeons
      in New South Wales in April 1999. Data collected included the type of practice,
      number of cholecystectomies performed, preoperative markers of CBD stones,
      indications for preoperative endoscopic retrograde cholangiopancreatography
      (ERCP), use of operative cholangiography (OC) and the management of CBD stones
      found on OC. RESULTS: The questionnaire was returned by 223 (57%) surgeons. Fifty
      four (14%) of these respondents were excluded as they did not perform
      laparoscopic cholecystectomy, leaving 169 (43%) respondents for analysis. The
      preoperative indicators for CBD stones were ranked as: jaundice > dilated CBD on
      ultrasound > serum bilirubin > serum alkaline phosphatase/alanine
      aminotransferase > previous biliary pancreatitis. Preoperative ERCP would be
      performed by 88% for persistent jaundice or cholangitis, 33% for elevated liver
      function test, 25% for dilated CBD and 24% for biliary pancreatitis. Operative
      cholangiography is routinely performed by 67%, selectively by 29% and never by
      4%. If CBD stones are encountered 47% would attempt laparoscopic clearance via
      the cystic duct or choledochotomy; however, 72% replied that they would use
      postoperative ERCP as part of their usual strategy for the management of CBD
      stones. CONCLUSIONS: There was no clear common pattern for the management of
      suspected or proven CBD stones. There were three management issues in which there
      was a 'common practice'. These were: (i) the use of preoperative ERCP for
      patients with persistent jaundice or cholangitis; and the routine use of (ii) OC
      and (iii) postoperative ERCP to clear the CBD, assuming other methods had failed.

PMID- 12071449
TI  - Selective use of preoperative endoscopic retrograde cholangiopancreatography in
      the era of laparoscopic cholecystectomy.
AB  - BACKGROUND: The use of endoscopic retrograde cholangiopancreatography (ERCP) in
      the management of suspected common bile duct (CBD) stones prior to laparoscopic
      cholecystectomy is common. The associated morbidity can be significant. The
      present study determines significant predictors of CBD stones and improves the
      selection of patients for preoperative ERCP. METHODS: All preoperative ERCP for
      suspected CBD stones in the year 1998 were studied retrospectively. Univariate
      and multivariate analyses of a number of clinical, biochemical and radiological
      variables were carried out to determine the best predictors of CBD stones.
      RESULTS: A total of 112 patients had successful preoperative ERCP. Sixty-one per
      cent of these were negative for stones and the morbidity was 9%. Univariate
      analysis revealed the following variables as predictors: cholangitis (P = 0.006),
      abnormal serum bilirubin > or = 3 days (P = 0.002), serum alkaline phosphatase >
      or = 130 U/L (P = 0.002), deranged liver function tests (P = < 0.001) and CBD
      diameter > or = 8 mm (P = 0.009) with positive predictive values of 80%, 68%,
      49%, 38% and 52%, respectively. Multivariate analysis revealed the model with the
      best ability to discriminate for CBD stones (P = 0.0005) was cholangitis,
      abnormal serum bilirubin for > or = 3 days and CBD diameter > or = 8 mm. The best
      predictors from this study had a sensitivity of 80% and a specificity of 27%.
      CONCLUSIONS: The predictors of CBD stones are imprecise. Until laparoscopic
      exploration of CBD becomes widely available, ERCP prior to cholecystectomy will
      remain popular. The use of stricter selection criteria can reduce the number of
      negative preoperative ERCP.

PMID- 12071450
TI  - Australian audit for the endoluminal repair of abdominal aortic aneurysm: the
      first 12 months.
AB  - BACKGROUND: The Australian Safety and Efficacy Register for New Interventional
      Procedures - Surgical (ASERNIP-S) was contracted by the Commonwealth Department
      of Health and Aged Care to audit the procedure of endoluminal repair of abdominal
      aortic aneurysm. The purpose of the audit was to examine the safety and efficacy
      of the endoluminal graft (ELG) and, where possible, compare it to the open
      procedure. The first 12 months of data collection has now been completed. An
      overview of these results and some of the problems associated with the
      establishment of this audit are given. METHODS: The administrative infrastructure
      to support the audit is based at the ASERNIP-S office in Adelaide. To achieve
      high compliance rates, regular contact was maintained with surgeons. A reference
      group of senior vascular surgeons was established to provide expert support to
      the audit. RESULTS: By December 2000, ASERNIP-S had collected data on
      approximately 85% of privately performed ELG procedures during the first year of
      the audit. The early mortality rate was 1.3% in the endoluminal group compared to
      2.6% in the open group. The rate of procedural complications was 15% in both
      groups, but the percentage of systemic complications was higher following the
      open repair. Aneurysm size and the number of pre-existing conditions had a
      statistically significant relationship to the variation in the number of
      complications for ELG patients. CONCLUSIONS: Good compliance has been obtained
      from vascular surgeons for submission of the operative data sets. ASERNIP-S aims
      to follow this group of patients closely to assess the medium to long-term
      durability of this procedure.

PMID- 12071451
TI  - Proximal femoral osteotomy for the treatment of hip arthritis in young adults.
AB  - BACKGROUND: The outcome of proximal femoral osteotomy for hip arthritis in young
      adults performed at the Wellington Hospital (Wellington, New Zealand) was
      reviewed. METHODS: Seventeen patients underwent 21 proximal femoral osteotomies
      for the treatment of hip arthritis at Wellington Hospital between 1992 and 1999.
      Thirteen patients (17 hips) were contacted and were able to complete a
      questionnaire form specific for hip pain and function. RESULTS: There was a
      response rate of 76.5% (13 out of a possible 17 patients undergoing proximal
      femoral osteotomy) at a mean 3 years 4 months postoperatively. Of these, one
      patient has had a total hip joint replacement and one patient is currently on the
      waiting list for a total hip joint replacement. Three other patients (three hips)
      report moderate or severe hip pain. The remaining eight patients (12 hips) report
      having mild or no hip pain. Questionnaire results show a postoperative decrease
      in hip pain in most patients. Hip function as assessed by the questionnaire was
      essentially unchanged. CONCLUSIONS: Proximal femoral osteotomy is a satisfactory
      option for young patients with degenerative hip arthritis. The operation is only
      likely to be useful in the treatment of pain.

PMID- 12071452
TI  - Primary hyperparathyroidism: referral patterns and outcomes of surgery.
AB  - BACKGROUND: Parathyroidectomy has long been established as an effective treatment
      for primary hyperparathyroidism (HPT). METHODS: A 15-year retrospective audit was
      made by surgeons at North Shore Hospital, Auckland, of 33 patients with primary
      HPT who had parathyroidectomy. RESULTS: There were 22 females and 11 males,
      ranging in age from 18 to 77 years (median 63 years). Initial diagnosis was
      predominantly by a general practitioner (72%), who invariably referred to a
      physician. Referral to surgery was made by general physicians (55%),
      endocrinologists (33%) and geriatricians (6%). Delay between diagnosis and
      referral for surgery ranged from 8 days to 10 years (median 7 months), and
      exceeded 2 years in 24% of patients. Twenty-eight (85%) were symptomatic: 13
      (39%) had renal symptoms, 13 (39%) had bone disease, 10 (31%) had
      gastrointestinal complaints, seven (21%) had psychiatric illnesses and six (18%)
      had fatigue. The high incidence of symptoms was matched by high biochemical
      values (mean serum calcium level 2.97 mmol/L), and large parathyroid glands (mean
      weight 2001 mg). Twenty-nine patients (88%) had single adenomas, two (6%) had
      chief cell hyperplasia and two (6%) had carcinoma. Thirty-one (94%) were cured of
      their primary HPT. CONCLUSIONS: Parathyroidectomy is a safe and effective
      treatment for primary HPT but depends upon referral from non-surgical clinicians.
      A large proportion of patients have long delays before their surgery, and the
      group selected for surgery is referred with severe disease.

PMID- 12071453
TI  - When exactly can carpal tunnel syndrome be considered work-related?
AB  - BACKGROUND: Carpal tunnel syndrome (CTS), compression of the median nerve at the
      wrist, is the most frequently encountered peripheral entrapment neuropathy.
      Whilst rates of all other work-related conditions have declined, the number of
      work-related musculoskeletal disorders (which include CTS) has not changed for
      the past 9 years in the USA. Median days off work are also highest for CTS: 27
      compared to 20 for fractures and 18 for amputations. This results in enormous
      Workers Compensation and other costs to the community. Awareness of CTS as a
      disorder associated with repeated trauma at work is now so widespread amongst
      workers that many have diagnosed themselves before being medically assessed,
      often by means of the Internet. Surprisingly, however, a definite causal
      relationship has not yet been established for most occupations. Although the
      quality of research in this area is generally poor, CTS research studies are
      being used as the basis for acceptance of Workers Compensation claims,
      substantial expensive ergonomic workplace change and even workplace closures. The
      fact that the incidence of work-related musculoskeletal disorders has not changed
      despite these latter measures would suggest that a causal relationship is not
      proven and that some resources are being misdirected in CTS prevention and
      treatment. METHOD: A literature review of 64 articles on CTS was conducted. This
      included those articles most frequently cited as demonstrating the relationship
      between CTS and work. RESULTS: Primary risk factors in the development of CTS
      are: being a woman of menopausal age, obesity or lack of fitness, diabetes or
      having a family history of diabetes, osteoarthritis of the carpometacarpal joint
      of the thumb, smoking, and lifetime alcohol intake. In most cases, work acts as
      the 'last straw' in CTS causation. CONCLUSION: Except in the case of work that
      involves very cold temperatures (possibly in conjunction with load and
      repetition) such as butchery, work is less likely than demographic and disease
      related variables to cause CTS. To label other types of work as having caused
      CTS, therefore, would result in inappropriate allocation of resources. It would
      also relieve individuals of the responsibility of addressing correctable
      lifestyle factors and treatable illnesses such as obesity, diabetes, smoking and
      increased alcohol intake which may have contributed to their CTS more that their
      work. This results in both avoidable long-term health effects and ongoing costs
      to the community.

PMID- 12071454
TI  - 131I lipiodol therapy for unresectable hepatocellular carcinoma.
AB  - BACKGROUND: More than 80% of hepatocellular carcinoma tumours (HCC) are
      unresectable at presentation because of the multicentric nature of the disease or
      the severity of liver disease. Arterially administered lipiodol is preferentially
      retained by HCC and has been used as a vehicle for delivery of therapeutic agents
      to the tumour. The aim of this phase I study is to present the experience with
      131I-labelled lipiodol in the treatment of unresectable HCC. METHODS: 131Iodine
      lipiodol treatment was administered to 12 patients with unresectable HCC between
      1994 and 1999. The outcome of treatment in these patients was evaluated for
      survival, clinical tolerance, liver function tests, alpha-fetoprotein (AFP)
      levels and changes in tumour size on computed tomography (CT) scans. RESULTS: Ten
      of the 12 patients received more than one 131I treatment. Five patients had
      treatment for post-resection recurrence. Serum AFP levels dropped initially in
      five of the seven patients with elevated values. Tumour size, evaluated by CT
      scans at 3 months, decreased in six patients and remained stable in the rest,
      except one patient in whom both the AFP level and tumour size had increased.
      Using life table analysis, the 50% survival was 19 months. CONCLUSIONS: Intra
      arterial 131I treatment was very well tolerated. A reduction in AFP levels and
      tumour size occurred in half of the patients and resulted in a 50% probability of
      survival of 19 months. Further examination of the value of this treatment in
      phase II and III studies is required.

PMID- 12071455
TI  - Push enteroscopy: a single centre experience and review of published series.
AB  - BACKGROUND: To assess the efficacy of push enteroscopy in a single tertiary
      hospital and review the available literature to assess the overall diagnostic
      yield of push enteroscopy. METHODS: Review of a database on push enteroscopy in a
      tertiary hospital from 1997 to 1999. This included 100 consecutive patients who
      underwent push enteroscopy. Review of all large published series on push
      enteroscopy to date to obtain an overall diagnostic yield. RESULTS: The
      diagnostic yield for patients with gastrointestinal (GI) bleeding was 47% and for
      patients with suspected small bowel disease was 33%. Angiodysplasia was the most
      common diagnosis in patients with GI blood loss. Patients with active GI bleeding
      had a higher diagnostic yield. The procedure was tolerated well and no
      complications occurred. Review of the literature showed an overall diagnostic
      yield of 44% (498 of 1 136 patients) for patients with GI blood loss and 38% (108
      of 286 patients) for suspected small bowel disease. CONCLUSIONS: Push enteroscopy
      has a good diagnostic yield and is valuable in patients with GI blood loss and
      suspected small bowel disease.

PMID- 12071456
TI  - Incomplete excision of basal cell carcinomas: a retrospective audit.
AB  - BACKGROUND: The reported rates of incomplete excision of basal cell carcinoma
      (BCC) vary widely (5-25%) among centres around the world. Incomplete excision of
      skin malignancy is one of the 57 clinical indicators developed by the Royal
      Australasian College of Surgeons and the Australian Council on Healthcare
      Standards to act as a measure of the standard of surgical care. The study aims to
      determine the rate of incomplete excision of BCC at a major cancer centre.
      METHODS: Computerized data and patients' records were reviewed. From January 1997
      to June 2000, a total of 3558 BCC were surgically excised with curative intent,
      of which 223 were reported to have been removed incompletely. RESULTS: The
      overall rate of incomplete excision was 6.3%. CONCLUSIONS: Given the limitations
      of a retrospective audit and reliability of the data, this result nevertheless
      compares favourably with reported figures in the literature.

PMID- 12071457
TI  - Increased incidence of benign breast disease in female renal transplant patients
      receiving cyclosporin.
AB  - BACKGROUND: Unlike other cancers, breast cancer does not occur at increased
      frequency in renal transplant patients but fibroadenomata may be more common as a
      result of exposure to cyclosporin. In order to determine the incidence of benign
      breast disease in renal transplant patients at Monash Medical Centre, current
      female patients were studied. METHODS: The study was divided into two parts: (i)
      a retrospective review of those who presented with clinically detectable breast
      lumps; and (ii) mammographic screening of current female transplant patients who
      had been transplanted for more than 1 year. RESULTS: In the retrospective study
      there were 11 patients with 16 breast lumps among a total of 85 patients. All
      were confirmed by biopsy. The mean age at diagnosis of breast lumps was 41.5
      years (range 25-70 years). The mean time to presentation was 3.5 years after
      transplantation. Nine out of 11 patients had benign breast disease including
      fibroadenoma (six patients), fibrocystic disease (two patients) and intraductal
      papillomatosis (one patient). Two patients had breast cancer. Five of the
      patients with fibroadenoma had multiple lumps and a recurrent course. All
      patients with fibroadenomata had received cyclosporin. In the second part, 54
      patients were further screened. The mean duration of transplantation was 6.4
      years (range 1.25-18.5 years). Eighty-seven per cent of the patients had received
      cyclosporin, and 80% had a negative (normal) study. Seven of 54 had abnormalities
      including cysts and calcification, of whom two patients had fibroadenomata. Four
      patients had 'dense mammograms', all of whom received cyclosporin as a part of
      their immunosuppression. No breast cancer was detected during the study.
      CONCLUSION: The incidence of benign breast disease in the female transplant
      patients studied was far greater then the general population. The increase in
      fibroadenomata, in particular, may relate to the use of cyclosporin.

PMID- 12071458
TI  - Management of the acute scrotum in children.
AB  - BACKGROUND: The study investigates the hypothesis that testicular torsion is over
      diagnosed by emergency department (ED) doctors. Diagnoses made by ED doctors are
      compared with those made by a surgical registrar or specialist and the review
      outcome by a surgical registrar or specialist on diagnosis and management is
      evaluated. METHODS: Medical records of all boys up to the age of 14 years who
      presented with an acute scrotum to the ED at The Canberra Hospital between
      October 1995 and October 2000 were retrospectively reviewed. RESULTS: A total of
      182 boys presented to the ED on 190 occasions; mean age of presentation was 10.1
      years and mean time from onset of pain to presentation was 27.6 h. Ninety (47.4%)
      patients had a torted testicular appendage, 23 (12.1%) had testicular torsion and
      12 (6.3%) had epididymitis or orchitis. Eighty-one patients underwent surgery, in
      whom 61 were excluded from having testicular torsion. Testicular torsion was
      suspected by ED doctors in 57.5% of patients, by registrars in 35.4% and by
      specialists in 17.7%. Overall, the correct diagnosis was made by ED doctors in
      39% of patients, by registrars in 53% and by specialists in 76%. CONCLUSIONS:
      Less experienced examiners suspect testicular torsion more frequently than
      surgical registrars or specialists. Review of the patient by an experienced
      examiner should allow for more accurate initial diagnoses and spare some children
      unnecessary surgical procedures.

PMID- 12071459
TI  - Intestinal adaptation in short bowel syndrome.
AB  - Regaining enteral autonomy after extensive small bowel resection is dependent on
      intestinal adaptation. This adaptational process is characterized by hyperplastic
      growth of the remaining gut, which is accompanied by both an increase of cell
      division at the level of the crypt cells and by an increased rate of programmed
      cell death (apoptosis). Apart from the absorptive function, the small bowel also
      has a barrier function and plays an important role in interorgan metabolism.
      Also, these functions are greatly affected by a massive intestinal resection and
      subsequent recovery by intestinal adaptation. This review aims to give an
      overview of the debilitating effects of massive intestinal resection on gut
      function and subsequently discusses intestinal adaptation and possible factors
      stimulating adaptation.

PMID- 12071460
TI  - Importance of the external laryngeal nerve in thyroid surgery.

PMID- 12071462
TI  - Blunt trauma to the spleen.

PMID- 12071461
TI  - Editorial: the 'neglected' nerve in thyroid surgery--the case for routine
      identification of the external laryngeal nerve.

PMID- 12071463
TI  - Skin wrinkling for the assessment of sympathetic function in the limbs.

PMID- 12071464
TI  - Oesophageal leiomyoma: a case report.

PMID- 12071465
TI  - Intracranial dislocation of the mandibular condyle.

PMID- 12071466
TI  - Metastatic lung cancer causing bowel perforations: spontaneous or chemotherapy
      related?

PMID- 12071467
TI  - Effects of pinealectomy and melatonin on the retrograde degeneration of retinal
      ganglion cells in a novel model of intraorbital optic nerve transection in mice.
AB  - The effects of pinealectomy and of intraperitoneally administered melatonin on
      the retrograde degeneration of retinal ganglion cells (RGCs) were examined in a
      novel model of optic nerve (ON) transection in C57BL/16J mice. RGCs were
      prelabeled with the fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethyl
      indocarbocyanine perchlorate (Di-I), and the ON was cut inside the orbital cavity
      7 days later. The degree of RGC injury was assessed by counting viable Di-I
      labeled RGCs in various locations of the retina. In unlesioned control eyes, a
      mean ganglion cell density of 1,891 +/- 30/mm2 (mean +/- S.E.M.) was determined.
      The cell density markedly declined at 14 days after axotomy (295 +/- 9 cells/mm2;
      15.6% of contralateral). Sham-pinealectomy did not influence the density of RGCs
      at 14 days after ON transection (382 +/- 37 cells/mm2). In pinealectomized
      animals, on the other hand, the RGC number was significantly reduced as compared
      with untreated and sham-pinealectomized animals (91 +/- 33 RGCs/mm2). The effect
      of pinealectomy was reversed after i.p. administration of melatonin (4 mg/kg bw
      bolus followed by continuous infusion of 8 mg/kg bw/day) (286 +/- 27 cells/mm2).
      In nonpinealectomized animals, on the contrary, i.p. melatonin did not influence
      the RGC density (344 +/- 20 cells/mm2). The present results suggest that
      endogenous melatonin prevents the delayed degeneration of adult central nervous
      system (CNS) neurons in vivo, and that exogenous substitution of melatonin may be
      useful to protect injured neurons against cell death under conditions of
      melatonin deficiency, e.g. in the aged brain, when melatonin synthesis and
      secretion have decreased.

PMID- 12071468
TI  - Modulation of intracellular calcium and calmodulin by melatonin in MCF-7 human
      breast cancer cells.
AB  - The pineal hormone, melatonin, has been shown to inhibit the proliferation of the
      estrogen receptor alpha (ERalpha)-positive macrophage chemotactic factor (MCF)-7
      human breast cancer cells. Previous studies from other systems indicate that
      melatonin modulates the calcium (Ca2+)/calmodulin (CaM) signaling pathway either
      by changing intracellular calcium concentration ([Ca2+]i) via activation of its G
      protein coupled membrane receptors, or through a direct interaction with CaM. In
      this study, although melatonin alone had no effect on basal [Ca2+]i in MCF-7
      cells, it significantly enhanced the elevation of [Ca2+]i induction by
      extracellular adenosine triphosphate (ATP), which increases [Ca2+]i via the G
      protein-coupled P2y-purinoceptor and the phospholipase C (PLC) pathway.
      Pretreatment of MCF-7 cells with 10(-7) M melatonin increased the 10(-5) M ATP
      induced [Ca2+]i peak change from 79.4 +/- 11.6 nM to 146.2 +/- 22.3 nM.
      Furthermore, without changing total cellular CaM levels, melatonin markedly
      increased the amount of membrane-bound CaM to 237 and 162% of control levels
      after I and 6 hr of treatment, respectively. Cytosolic CaM levels were also
      elevated to 172% of control after 6 hr of melatonin treatment. Correlative growth
      studies demonstrated that ATP (10(-5) M) can stimulate MCF-7 cell growth, that
      melatonin can suppress MCF-7 cell proliferation, but that pretreatment of MCF-7
      cells with melatonin followed by ATP(10(-5) M), like 10(-4) M ATP can further
      suppress MCF-7 cell proliferation; this indicates that melatonin's potentiation
      of ATP induced [Ca2+]i may be above the threshold for cell growth. Given the
      important role of [Ca2+]i and CaM in tumor cell homeostasis and proliferation and
      melatonin's modulation of [Ca2+]i, melatonin's effects on the Ca2+/CaM signaling
      pathway may play an important role in mediating the growth-inhibitory effect of
      melatonin on MCF-7 human breast cancer cells.

PMID- 12071469
TI  - The protective effect of melatonin on renal ischemia-reperfusion injury in the
      rat.
AB  - Oxygen free radicals are considered to be important components involved in the
      pathophysiological tissue alterations observed during ischemia-reperfusion (I/R).
      In this study, we investigated the putative protective effects of melatonin
      treatment on renal I/R injury. Wistar albino rats were unilaterally
      nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 1,
      3, 6, 24, 48 hr or 1 wk of reperfusion. Melatonin (10 mg/kg, s.c.) or vehicle was
      administered twice, 15 min prior to ischemia and immediately before the
      reperfusion period. At the end of the reperfusion periods, rats were decapitated.
      Kidney samples were taken for histological examination or the determination of
      renal malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO)
      activity and protein oxidation (PO). Serum creatinine and blood urea nitrogen
      (BUN) concentrations were measured for the evaluation of renal function. The
      results revealed that I/R induced nephrotoxicity, as evidenced by increases in
      BUN and creatinine levels at each time point, was reversed by melatonin
      treatment. The decrease in GSH and increases in MDA, MPO and PO induced by I/R
      indicated that renal injury involves free radical formation. As melatonin
      administration reversed these oxidant responses, improved renal function and
      microscopic damage, it seems likely that melatonin protects kidney tissue against
      oxidative damage.

PMID- 12071470
TI  - Melatonin attenuates the neuronal NADPH-d/NOS expression in the nodose ganglion
      of acute hypoxic rats.
AB  - Excessive production of nitric oxide (NO) may play a detrimental role in the
      process of hypoxia-related neuropathology. This study explored whether treatment
      with melatonin would attenuate the neuropathological changes in the vagal ganglia
      following a severe hypoxic insult. Thirty minutes prior to hypoxia treatment,
      young adult rats were pre-treated with melatonin at 5. 25 or 100 mg/kg injected
      intraperitoneally. Hypoxia was achieved by subjecting the rats to a barometric
      pressure of 0.2 atm (PO2 = 43 Torr) for 4 hr in an altitude chamber. Nicotinamine
      adenine dinucleotide phosphatediaphorase (NADPH-d) histochemistry combined with
      the neuronal nitric oxide synthase (nNOS) immunohistochemistry were used to
      detect the NADPH-d/nNOS reactivity in the nodose ganglion (NG) at various time
      points following the hypoxic exposure. In normal untreated rats, about 43% of the
      neurons in the NG displayed NADPH-d/nNOS reactivity. Following hypoxic exposure,
      both the percentage and the staining intensity of NADPH-d/nNOS positive neurons
      in the NG were markedly increased, but these were reduced in longer surviving
      animals. Quantitative analysis of cell counts revealed that about 17% of the
      neurons died at 14 days after hypoxia treatment. However, in hypoxic rats given
      different doses of melatonin pretreatment, neuronal death as well as the
      frequency and staining intensity of NADPH-d/nNOS reactivity of the nodose neurons
      were significantly decreased. The effect of melatonin on neuronal survival and
      NADPH-d/ nNOS expression was dose-dependent. It is therefore suggested that
      melatonin exerts a neuroprotective effect and may serve as a potential
      therapeutic strategy for prevention and/or reducing the susceptibility of nodose
      neurons to NO-mediated hypoxic neuropathy.

PMID- 12071471
TI  - First cloning and functional characterization of a melatonin receptor in fish
      brain: a novel one?
AB  - Melatonin, a neuroendocrine transducer of photoperiod, influences a number of
      physiological functions and behaviors through specific seven transmembrane
      domains receptors. We report here the first full-length cloning and functional
      characterization of a melatonin receptor (P2.6) in a fish, the pike (Teleost).
      P2.6 encodes a protein that is approximately 80% identical to melatonin receptors
      previously isolated partially in non-mammals and classified as members of the
      Mel(1b) subtype; but, it shares only 61% identity with the full-length human
      Mel(1b) melatonin receptor (hMT2). Expression of P2.6 results in ligand binding
      characteristics similar to that described for endogenous melatonin receptors.
      Selective antagonists of the hMT2 (4-phenyl-2-propionamidotetraline and
      luzindole) were poor competitors of 2-[125I]iodomelatonin binding to the
      recombinant receptor. In Chinese hamster ovary cells expressing both the cystic
      fibrosis transmembrane conductance regulator chloride channel and P2.6 receptor,
      melatonin counteracted the forskolin induced activation of the channel. The
      results are best explained by a selective inhibition of the adenylyl cyclase. By
      reverse transcription-polymerase chain reaction, P2.6 mRNA appeared expressed in
      the optic tectum and, to lesser extent, in the retina and pituitary. In
      conclusion, these results, together with those of a phylogenetic analysis,
      suggest that P2.6 might belong to a distinct subtype group within the vertebrate
      melatonin receptor family.

PMID- 12071472
TI  - The protective effects of melatonin from oxidative damage induced by amyloid beta
      peptide 25-35 in middle-aged rats.
AB  - This work investigated the ability of melatonin to prevent oxidative damage in
      brain tissue induced by injection of beta-amyloid peptide 25-35 (Abeta25-35) in
      middle-aged rats. The Morris water maze was used to evaluate the cognitive
      function of the rats. Thiobarbituric acid-reactive substances and antioxidative
      enzymes (superoxide dismutase and glutathione peroxidase) activities were
      measured. It was found that injection of (Abeta25-35) (20 microg) into the rat
      hippocampus caused an increase in the latency (the time to find the platform),
      the total swimming distance to the platform, and the starting angles in (Abeta25
      35)-treated rats. Furthermore, a significant rise in lipid peroxidation and
      decrease in antioxidative enzyme activities in brain tissue were found. Melatonin
      (0.1, 1, and 10 mg/kg, i.g. x 10 days) improved the spatial resolution of amnesic
      rats in the Morris water maze test. Meanwhile, melatonin antagonized the lipid
      peroxidation in both the mitochondria (P < 0.01) at the doses of 0.1, 1.0, and 10
      mg/kg and in the cytoplasm at the doses of 0.1 and 1.0 mg/kg. Also in the amnesic
      rats, melatonin (0.1, 1.0, and 10 mg/kg. i.g. x 10 days) stimulated the
      antioxidative enzyme activities. The results show that melatonin effectively
      reduced lipid peroxidation and enhanced the antioxidative enzyme activities in
      Abeta(25-35)-treated rats, which may contribute to the improvement of rats'
      learning and memory impaired by Abeta(25-35).

PMID- 12071473
TI  - Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro?
AB  - Melatonin inhibits proliferation of the estrogen-responsive MCF-7 human breast
      cancer cells. The objective of this work was to assess whether melatonin not only
      regulates MCF-7 cell proliferation but also induces apoptosis. In this experiment
      we used 1,25-dihydroxycholecalciferol (D3) as a positive control because it
      inhibits MCF-7 cell proliferation and induces apoptosis. MCF-7 cells were
      cultured with either I nM melatonin, 100 nM D3 or its diluent to determine their
      effects on cell proliferation, cell viability, cell-cycle phase distribution,
      population of apoptotic cells, and expression of p53, p21WAF1, bcl-2, bcl-X(L)
      and bax proteins. After 24 or 48 hr of incubation, both melatonin and D3
      treatment significantly decreased the number of viable cells in relation to the
      controls, although no differences in cell viability were observed between the
      treatments. The incidence of apoptosis, measured as the population of cells
      falling in the sub-G1 region of the DNA histogram, or by the TUNEL reaction, was
      similar in melatonin-treated and control cells whereas, as expected, apoptosis
      was higher among cells treated with D3 than in controls. The expression of p53
      and p21WAF1 proteins significantly increased after 24 or 48 hr of incubation with
      either melatonin or D3. No significant changes in bcl-2, bcl-XL and bax mRNAs
      were detected after treatment with melatonin whereas in D3-treated cells, a
      significant drop in bcl-XL was observed. These data support the hypothesis that
      melatonin reduces MCF-7 cell proliferation by modulating cell-cycle length
      through the control of the p53-p21 pathway, but without clearly inducing
      apoptosis.

PMID- 12071475
TI  - The conference on the epidemiology of medical devices in women.

PMID- 12071474
TI  - 2[125I]Iodomelatonin binding sites in guinea pig platelets.
AB  - Using 2[125I]iodomelatonin as the radioligand, we characterized
      2[125I]iodomelatonin binding sites in guinea pig platelet membrane preparations.
      Saturation radioreceptor studies indicated that these 2[125I]iodomelatonin
      binding sites were of picomolar affinity and femtomolar density. The dissociation
      constant (Kd) and maximum number of receptor sites (Bmax) were 42.5 +/- 1.79 pM
      and 11.8 +/- 0.8 fmol/mg protein (n = 6), respectively. 2[125I]Iodomelatonin
      competition studies with indoles or drugs indicate the following rank order of
      potency: 2-iodomelatonin > melatonin > 6-chloromelatonin > 6-hydroxymelatonin > N
      acetylserotonin > 5-methoxytryptophol, whereas serotonin and its analogs had less
      than 20% inhibition at 0.1 mM. Guanosine 5'-O-(3-thiotriphosphate) significantly
      increased the Kd by twofold suggesting that these binding sites are coupled to
      the guanine nucleotide binding proteins. Immunoblotting studies using anti-MT(1)
      IgG demonstrated one peptide blockable band with an apparent molecular mass of 37
      kDa. Melatonin had no effect on prostacyclin or forskolin-stimulated
      intracellular 3',5'-cyclic adenosine monophosphate accumulation. A diurnal
      variation in binding density, which was abolished after the animals were adapted
      to constant light conditions, was observed. Age related studies demonstrated that
      Bmax increased as the animal matured. Physiological melatonin concentrations
      potentiated whereas those at pharmacological levels inhibited adenosine
      diphosphate- or arachidonic acid-stimulated platelet aggregation. Our study
      demonstrated G-protein coupled, saturable, reversible and highly specific
      picomolar affinity 2[125I]iodomelatonin binding sites in guinea pig platelets.
      Pharmocological and physiological data indicate that they may be different from
      the nanomolar [3H]melatonin binding sites in human platelets previously reported.

PMID- 12071476
TI  - Data sources: use in the epidemiologic study of medical devices.
AB  - Medical device epidemiology is the study of the prevalence and incidence of use,
      effectiveness, and adverse events associated with medical devices in a
      population. The identification of large data sources with medical device data
      provides a large population for epidemiologic studies. Two challenges in medical
      device epidemiology are the ability to find data on the specific device and the
      exposure of a patient to that device. This paper identifies data sources both
      from the govenment and from the private sector that can be used for epidemiologic
      studies of medical devices and, to a limited degree, studies of medical devices
      in women. Each source provides data for different types of devices and in
      differing specificity. The paper also discusses briefly the strengths and
      weaknesses of each data source. More data sources are needed to enhance the study
      of medical device epidemiology. Additional efforts and focus are needed to
      enhance the ability to study medical devices in women.

PMID- 12071477
TI  - Home and point-of-care pregnancy tests: a review of the technology.

PMID- 12071478
TI  - The safety of prenatal ultrasound exposure in human studies.
AB  - Diagnostic ultrasound use in obstetrics has been growing rapidly to become an
      integral part of prenatal care today. The high proportion of exposure to prenatal
      ultrasound highlights the public health significance of routine ultrasound use. A
      majority of epidemiologic studies tends to support the safety of diagnostic
      ultrasound use during pregnancy. However, there have been some reports that there
      may be a relation between prenatal ultrasound exposure and adverse outcome. Some
      of the reported effects include growth restriction, delayed speech, dyslexia, and
      non-right-handedness associated with ultrasound exposure. Continued research is
      needed to evaluate the potential adverse effects of ultrasound exposure during
      pregnancy. These studies should measure the acoustic output, exposure time,
      number of exposures per subject, and the timing during the pregnancy when
      exposure(s) occurred, while controlling for potential confounding variables such
      as sociodemographic, medical, and obstetric risk factors. We recommend that a new
      consensus development conference be held to gather the needed data and provide
      guidelines for the future research needs, as well as respond to the rapid
      advances in this technology.

PMID- 12071479
TI  - Introduction to and update of "cost effectiveness in new technology in cervix
      cancer screening".

PMID- 12071480
TI  - Cost effectiveness in new technology in cervix cancer screening.
AB  - The new techniques in cervix cancer screening are reviewed. Literature relevant
      to the performance and cost effectiveness of these technologies is reviewed.
      Literature relevant to cost effectiveness of other techniques used for cervix
      cancer screening is reviewed. Prospective trials of competing technology are
      proposed to resolve the question utilizing contemporaneous methods of assessing
      cost effectiveness.

PMID- 12071481
TI  - The primary screening clinical trials of the TriPath AutoPap System.
AB  - The AutoPap Primary Screening System has been approved recently by the United
      States Food and Drug Administration for the initial screening and quality control
      of non-"high-risk" conventional cervical cytology slides. A prospective clinical
      trial using the device compared its performance in terms of sensitivity and
      specificity for abnormality detection with the current standard of practice,
      which is represented by initial manual screening and 10% random quality control
      rescreening. The study showed statistically superior abnormality detection
      sensitivity by the AutoPap System. In addition, specificity of diagnosis was also
      improved. Equivalent performance was noted for categorization of slide adequacy
      and detection of infectious organisms and benign cellular changes. Use of the
      AutoPap System therefore has the potential to improve the accuracy of cervical
      cytologic examinations as well as to make a positive impact on the productivity
      of cytology laboratory personnel.

PMID- 12071483
TI  - New-device angioplasty in women: outcomes of planned and unplanned use.
AB  - New interventional devices for treatment of coronary artery disease are used in
      planned mode for the definitive treatment of lesions with particular morphology,
      and in unplanned mode after failure or suboptimal conventional balloon
      angioplasty. This report from the New Approaches to Coronary Intervention
      Registry describes the baseline characteristics and short- and long-term outcomes
      of men (N = 840) and women (N = 721) treated with one of seven new devices in
      planned and unplanned modes. For both planned and unplanned attempts, women were
      older than the men by approximately 5 years and were more likely to have diabetes
      (25% vs 16%) and hypertension (64% vs 46%). Lesions treated with planned new
      devices were more frequently in the right coronary artery in women and in an
      ostial location. There were few differences seen in the lesions treated with
      unplanned devices. In-hospital success was good for all groups, although men with
      unplanned attempts fared somewhat less well than the women (procedural success
      90% for women vs 79% for men). At 1 year, the combination endpoint of death/Q
      wave myocardial infarction/repeat revascularization was 32% for women vs 49% for
      men in the unplanned group, and 32% vs 38% in the planned group.

PMID- 12071482
TI  - Epidemiology of silicone-gel breast implants.
AB  - Silicone breast implants have been marketed in the United States since 1963.
      Questions remain unanswered on the safety of these medical devices despite their
      popularity and availability. In 1992, the Food and Drug Administration restricted
      the availability of silicone-gel breast implants to women requiring them for
      reconstruction after breast cancer or for other medical indications. Inflatable
      saline breast implants have remained available for either reconstruction or for
      cosmetic augmentation while manufacturers completed studies addressing issues of
      safety and effectiveness. The Food and Drug Administration (FDA) has less concern
      today regarding a putative association between breast implants and autoimmune
      disease because of epidemiologic studies that have indicated that there is not a
      large increase in risk for connective tissue disease in women with breast
      implants. These studies have not ruled out a small increase in risk of connective
      tissue disease to these women nor have they addressed the issue of an atypical
      syndrome related to silicone. The FDA has continuing concerns over local
      complications that are related to breast implants. The current review provides a
      brief discussion of the regulatory history of silicone implants and of FDA
      concerns over breast implants, implant prevalence, studies of systemic and local
      complications related to breast implants, and a brief description of the FDA
      study of silicone-gel breast implant rupture.

PMID- 12071485
TI  - Biobehavioral mechanisms of work-related upper extremity disorders: a new agenda
      for research and practice.
AB  - BACKGROUND: Epidemiological studies provide support for the role of
      organizational and individual psychosocial stressors in work-related upper
      extremity disorders (WRUEDs). Despite this evidence, the biological plausibility
      of a relationship between exposure to various psychosocial and work
      organizational stressors and WRUEDs remains unclear METHODS: The Georgetown
      Symposium on Biobehavioral Mechanisms of Work-Related Upper Extremity Disorders
      was held in Washington D.C. on November 6-7, 2000 to improve the understanding of
      potential biobehavioral mechanisms, identify future areas for research and
      discuss the implications of this body of knowledge for intervention. This meeting
      involved presentations and discussions by researchers and clinicians from a
      number of disciplines (epidemiology, occupational medicine, rheumatology,
      orthopedics, surgery, internal medicine, psychoneuroimmunology, occupational
      health psychology, behavioral medicine, psychophysiology and experimental and
      organizational psychology). RESULTS: The symposium generated several papers
      addressing the following topics: definitions and job stress models;
      epidemiological foundations; musculoskeletal and biomechanical models; central
      nervous system models of recurrent and persistent clinical pain; psychophysiology
      of work; and implications for intervention. These papers comprise this special
      issue. DISCUSSION: The present paper summarizes the various contributions to this
      special issue and provides direction for future research on potential
      biobehavioral pathways.

PMID- 12071484
TI  - New-device angioplasty in women: clinical outcome and predictors in a 7,372
      patient registry.
AB  - BACKGROUND: Female gender has been identified as an independent predictor of
      early complications and mortality after conventional balloon angioplasty. To gain
      insight into the outcome of women after new-device angioplasty, we reviewed the
      early and late clinical outcome of 7,372 patients undergoing new-device
      angioplasty between 1991 and 1996 at the Washington Hospital Center. METHODS:
      Patients (2,077 women and 5,295 men) with native coronary artery (82.5%) or
      saphenous vein graft lesions undergoing new-device angioplasty were included in
      the study. In-hospital and 1-year major adverse cardiac events (MACE), including
      death, myocardial infarction, and target lesion revascularization (TLR), were
      recorded and compared on the basis of gender. Multivariable logistic regression
      analysis was performed to identify predictors of in-hospital and late mortality,
      follow-up MACE, and TLR. RESULTS: Women had more baseline comorbid risk factors
      and smaller reference vessel size compared with men. Women had a higher in
      hospital cardiac mortality (1.39% vs 0.66%, P = 0.002), TLR (2.78% vs 1.81%, P =
      0.008), and congestive heart failure (4.18% vs 2.29%, P < 0.001) compared with
      men. Overall in-hospital MACE tended to be higher among women (4.2% vs 3.3%, P =
      0.074). Women had a higher 1-year mortality rate (4.39% vs 3.26%, P = 0.018), but
      a lower follow-up TLR (15.0% vs 18.1%, P = 0.001) and a lower overall MACE rate
      (29.2% vs 32.7%, P = 0.007) compared with men. Female gender was an independent
      predictor of in-hospital mortality (odds ratio 2.28, P = 0.02), but not late
      mortality. CONCLUSIONS: Although female gender appears to carry an inherent risk
      of in-hospital mortality after new-device angioplasty, the procedural success and
      mortality rates are favorable compared with those associated with balloon
      angioplasty series. The long-term clinical outcome of women after new-device
      angioplasty is excellent. The use of new devices is a safe and effective
      alternative strategy for the treatment of women with ischemic coronary artery
      disease. Device-specific outcomes, including stents, will require further
      evaluation.

PMID- 12071486
TI  - Occupational stress and work-related upper extremity disorders: concepts and
      models.
AB  - BACKGROUND: While research has suggested that interventions targeted at
      occupational stress (job stress) factors may improve clinical and work outcomes
      related to work-related musculoskeletal disorders, the emerging hypotheses
      relating occupational stress to work-related upper extremity disorders (WRUEDs)
      are not particularly well known among occupational health providers and
      researchers. METHODS: Generic job stress and health models and multivariable
      models of WRUEDs were described and evaluated. RESULTS: Models on occupational
      stress and health/WRUEDs offer unique perspectives on the role of occupational
      stressors on WRUEDs. However, the limited support for the structure and proposed
      mechanisms of these models suggest that investigations examining and validating
      proposed biobehavioral pathways are still needed. DISCUSSION: Difficulties in
      conceptualizing occupational stress have, in the past, hindered its systematic
      incorporation into occupational health research and prevention/intervention
      strategies. The present paper provides a common basis for researchers and
      practitioners with diverse backgrounds to understand job stress and its relation
      to WRUEDs in order to enhance future efforts. Given the present limitations in
      the field and the need for comprehensive approaches to WRUEDs, there is great
      potential for occupational health researchers and clinicians to advance knowledge
      in this area.

PMID- 12071488
TI  - Multilevel nerve compression and muscle imbalance in work-related neuromuscular
      disorders.
AB  - BACKGROUND: Work-related upper limb disorders have come under increasing scrutiny
      and become a frustrating problem. METHODS: A unifying hypothesis to explain the
      multiplicity of symptoms with work related neuromuscular disorders is outlined.
      This multifactorial problem includes physical, individual, and psychosocial
      factors. Abnormal postures and positions may compress nerves or may alter muscle
      length resulting in secondary compressive forces on nerves or in muscle
      imbalances. Evaluation should identify all nerve compression levels and muscle
      imbalance in the arm and cervicoscapular region. Management must include patient
      education, postural correction, and an exercise program to address the multiple
      nerve compression levels and muscle imbalance. RESULTS AND CONCLUSIONS: The
      etiology of work related neuromusculoskeletal disorders is multifactorial and
      successful management must address all contributing factors. Appropriate
      conservative management will relieve symptoms in most patients. Surgery should be
      reserved for those few patients with evidence of a specific diagnosis who have
      failed conservative management.

PMID- 12071487
TI  - Are psychosocial factors, risk factors for symptoms and signs of the shoulder,
      elbow, or hand/wrist?: A review of the epidemiological literature.
AB  - BACKGROUND: In 1993, an extensive review on the role of psychosocial factors in
      the development of musculoskeletal problems was published by Bongers et al
      (1993). Since then, additional reviews on this topic have been published;
      however, none of these focussed on upper limb problems. METHODS: In this
      systematic review, the methodological quality of all studies was assessed and
      levels of evidence were apriori defined. RESULTS: The large majority of the
      studies reported an association between at least one work-related psychosocial
      factor and adverse upper extremity symptoms or signs. High-perceived job stress
      was consistently associated with all upper extremity problems (UEP) in high and
      lower quality studies. Although not often studied, non-work-related stress was
      also consistently associated with UEP. In addition, there was some evidence for a
      relationship between high job demands and UEP, although the results did not meet
      the pre-set criterion for consistency. CONCLUSIONS: High job stress and non-work
      related stress reactions are consistently associated with UEP. In addition, high
      job demands is also in most studies associated with these disorders. Firm
      conclusions on the role of these factors in the etiology of UEP are not possible
      due to the cross-sectional nature of most studies.

PMID- 12071489
TI  - Biomechanical models for the pathogenesis of specific distal upper extremity
      disorders.
AB  - BACKGROUND: Knowledge of the pathogenesis of most disorders that occur in the
      distal upper extremity is generally lacking. The individual roles of postulated
      etiologic factors, such as biomechanical or psychosocial exposures, are poorly
      understood and their potential interactions even less so. This article proposes
      biomechanical or physiological models of pathogenesis for specific distal upper
      extremity disorders. METHODS: Tendon entrapment of the dorsal wrist compartments
      (tenosynovitis), peritendinitis, lateral epicondylitis, and carpal tunnel
      syndrome are common specific neuromusculoskeletal disorders of the upper
      extremities observed among workers. The normal anatomy and function of the
      targeted structures is considered the initial state; their pathology is
      considered the final state. Using biomechanical or physiological principles
      combined with clinical observations and experimental studies, pathways leading
      from the initial state to the final state are proposed. Each model defined a
      critical biomechanical or physiological attribute that was considered to best
      characterize 'dose.' Two temporal patterns of exposure (duration vs. repetition)
      were used to characterize 'dosage.' The roles of long-term exposure vs.
      unaccustomed work were mentioned, but not incorporated into the models. RESULTS:
      Compressive force transmitted to the extensor retinaculum was considered the
      critical factor in the model for tendon entrapment at the dorsal wrist
      compartments. Two models were proposed for lateral epicondylitis. One emphasized
      the role of eccentric exertions; the other emphasized contact pressure from the
      radial head. The model for peritendinitis relied on localized muscle fatigue.
      Seven plausible models were presented for carpal tunnel syndrome. CONCLUSIONS: It
      is possible to propose biologically plausible models of pathogenesis that are
      both coherent with current knowledge of tissue responses and consistent with
      clinical observations; however, more than one model was plausible for some
      conditions. Additional research is needed to determine which, if any, of the
      proposed models might be correct. Such models may be useful to health care
      providers and ergonomists in the context of primary, secondary, or tertiary
      prevention.

PMID- 12071490
TI  - Relationship between stress and pain in work-related upper extremity disorders:
      the hidden role of chronic multisymptom illnesses.
AB  - BACKGROUND: Pain and fatigue are commonly associated with work-related upper
      extremity disorders. Occasionally these symptoms persist beyond a reasonable
      healing period. One potential explanation for prolonged symptom expression is the
      concurrent development of a stress-mediated illness or CMI (Chronic Multi-Symptom
      Illness). In such a scenario, the chronic regional pain and other symptoms that
      the individual is experiencing would be attributable to the CMI rather than to
      tissue damage or a biomechanical dysfunction of the upper-extremity. METHODS:
      This article critically reviews the case definitions of the new class of CMI
      disorders and evaluates the existing evidence supporting centrally mediated
      physiological changes (e.g., sensory hypervigilance, dysautonomia) that manifest
      as symptoms of pain and fatigue in some individuals experiencing chronic
      stressors. RESULTS: While explanations for prolonged pain and fatigue have
      historically focused on mechanisms involving peripheral pathology or psychiatric
      explanations, ample evidences support the role of altered Central Nervous System
      function in accounting for symptom manifestation in CMI. CONCLUSIONS: A model is
      presented that unites seemingly disparate findings across numerous investigations
      and provides a framework for understanding how genetics, triggering events,
      stressors, and early life events can affect CNS activity. Resultant symptom
      expression (e.g., pain and fatigue) from central dysregulation would be expected
      to occur in a subset of individuals in the population, including a subset of
      individuals with work-related upper extremity disorders. Thus when symptoms such
      as pain and fatigue persist beyond a reasonable period, consideration of CMI and
      associated assessment and interventions focused on central mechanisms may be
      worthwhile.

PMID- 12071491
TI  - Psychophysiology of work: stress, gender, endocrine response, and work-related
      upper extremity disorders.
AB  - BACKGROUND: Mental stress may induce muscle tension and has been proposed to
      contribute to the development of work related upper extremity disorders (WRUEDs)
      by driving low threshold motor units into degenerative processes by overload.
      METHODS AND RESULTS: Measurements of perceived stress, catecholamines, blood
      pressure, and heart rate are associated with stress induced elevation of
      trapezius electromyographic activity. In repetitive tasks, where WRUEDs are
      common, psychophysiological arousal is generally high both during and after work.
      A possible explanation of the high prevalence of WRUEDs among women could be that
      women often are performing repetitive tasks and are exposed to additional stress
      from unpaid work. CONCLUSIONS: It is concluded that both physical and
      psychosocial work conditions may contribute to WRUEDs by inducing physiological
      stress and muscle tension.

PMID- 12071492
TI  - Daytime trapezius muscle activity and shoulder-neck pain of service workers with
      work stress and low biomechanical exposure.
AB  - AIM: The study aims to look for an association between trapezius muscle activity
      and shoulder-neck pain in work situations characterized by work stress and low
      biomechanical exposure. METHODS: Female subjects (n = 93) were recruited from
      four occupational groups: health care, shop assistants, banking, and university
      secretaries. Thirty-eight workers were interviewed and classified as pain
      afflicted by their shoulder-neck pain score in the last 6 months; 55 were pain
      free. Shoulder-neck pain, bodily state of tension and fatigue, and subjective
      exposure assessments were monitored by repeated hourly measurements over 24 hr.
      Trapezius muscle activity was recorded bilaterally by surface EMG. RESULTS:
      Shoulder-neck pain, perceived tension, work stress ("stressful environment"), and
      mental fatigue was augmented over the workday and reduced leisure time. Physical
      fatigue was low and stable. Thus, work stress appeared to be the dominant
      exposure associated with shoulder-neck pain. Muscle activity was low and similar
      for pain-afflicted and pain-free subjects during working hours. It was unchanged
      from work to leisure for the pain-afflicted workers and was significantly reduced
      for the pain-free group. CONCLUSIONS: Stress-induced shoulder and neck pain is
      not necessarily associated with elevated trapezius muscle activity, but pain-free
      workers may benefit from better muscle relaxation in leisure.

PMID- 12071493
TI  - Forearm EMG response activity during motor performance in individuals prone to
      increased stress reactivity.
AB  - BACKGROUND: Work-related Upper Extremity Disorders (WRUEDs) are conceived of as a
      multifactorial syndrome caused by the effects of excessive repetitive motions,
      sustained static postures, and muscular stiffness. Our aim is to test an
      etiological model derived from a theory by Van Galen and Van Huygevoort [2000]
      Biol Psychol 51:151-171. The theory holds that physical, emotional, and
      psychosocial stressors enhance muscular stiffness as a compensatory filtering of
      impoverished signal-to-noise ratios in the motor system. High individual levels
      of arousal, as measured by Spielberger et al. [1970], State and Trait Anxiety
      Test would further enhance a subject's predisposition to react with stiffness
      responses in conditions of stress. METHODS: Ten participants with a high- and 10
      with a low trait-anxiety score performed a computer task involving series of fast
      but well-dosed accelerations of the forearm along the surface of a digitizer. To
      induce cognitive stress a tone had to be remembered simultaneously with the
      aiming task. Pen-tip displacements and surface electromyographic (EMG) signals
      were recorded from four forearm muscles. RESULTS: Memory load did not affect
      error rates but produced shorter reaction times and prolonged movement times. EMG
      data show that under stress overall levels of neuromotor activation were
      enhanced. High-anxious participants exhibited higher cocontraction levels than
      low-anxious participants. CONCLUSIONS: The findings support the view that stress
      and muscular tension are closely related and may provide a clue to the origin of
      WRUEDs.

PMID- 12071494
TI  - A hyperventilation theory of job stress and musculoskeletal disorders.
AB  - BACKGROUND: There is evidence of a link between job stress and upper extremity
      work-related musculoskeletal disorders. However, the biobehavioral mechanisms by
      which psychosocial stress factors contribute to the development of
      musculoskeletal disorders are uncertain. METHODS: Based on established principles
      of breathing and job stress and the relevant empirical literatures, a
      hyperventilation theory of job stress and work-related musculoskeletal disorders
      was developed. RESULTS: Hyperventilation (overbreathing) refers to a drop in
      arterial CO2 caused by ventilation that exceeds metabolic demands for O2.
      Excessive loss of CO2 (increase in rate of flow of CO2 from cells to longs) that
      results from hyperventilation produces a rise in blood pH (i.e., respiratory
      alkalosis). This disruption in the acid-base equilibrium triggers a chain of
      systemic physiological reactions that have adverse implications for
      musculoskeletal health, including increased muscle tension, muscle spasm,
      amplified response to catecholamines, and muscle ischemia and hypoxia.
      Hyperventilation is often characterized by a shift from a diaphragmatic to a
      thoracic breathing pattern, which imposes biomechanical stress on the
      neck/shoulder region due to the ancillary recruitment of sternocelidomastoid,
      scalene, and trapezius muscles in support of thoraci breathing. CONCLUSIONS: A
      hyperventilation theory provides an innovative framework for understanding how
      job stress contributes to pathophysiological processes that increase the risk of
      work-related musculoskeletal disorders. With respect to the control of these
      disorders, a hyperventilation theory has important implications for establishing
      effective work organization interventions and individual stress-management
      methods. In this regard, breathing is a biobehavioral metric for assessing
      whether psychosocial aspects of work organization are in balance with a worker's
      needs and resources. A hyperventilation theory also provides a unique rationale
      for coping with job stress and musculoskeletal discomfort through breathing
      training, light physical exercise, and rest breaks.

PMID- 12071495
TI  - Early identification and intervention in the prevention of musculoskeletal pain.
AB  - BACKGROUND: A large number of people suffer from upper extremity disorders, but a
      few apparently consume the majority of the resources. Early interventions are
      badly needed to prevent the development of persistent disability. Since
      psychological factors are central in the development of a chronic problem these
      might be utilized in this endeavor. METHODS: A series of studies are described
      where a screening procedure based on psychological risk factors was employed to
      help identify people at risk for developing long-term work disability. The
      utility of a cognitive-behavioral group intervention that focuses on coping
      strategies as prevention was assessed in three randomized-controlled studies
      where participants had low, medium, and high risk, respectively. RESULTS: The
      study with low risk showed no significant difference between the groups, while
      the studies with medium- and high-risk populations demonstrated significantly
      lower work disability than control groups receiving treatment as usual.
      CONCLUSIONS: It appears to be feasible to identify patients with high levels of
      risk and to subsequently lower the risk for work disability by administering a
      cognitive-behavioral intervention focusing on psychological aspects of the pain
      problem.

PMID- 12071496
TI  - Stress and work-related upper extremity disorders: implications for prevention
      and management.
AB  - BACKGROUND: A causal link between stress and work-related musculoskeletal
      disorders of the upper extremities (WRUEDs) has been established, but there is
      less evidence for a beneficial effect of stress reduction interventions on WRUED
      symptoms and incidence. METHODS: Searches of Medline, Ergonomics Abstracts, and
      Psychlit from 1990 to 2001 identified studies that either targeted stress and
      measured WRUED outcomes, or described other interventions with both stress and
      WRUED outcomes. RESULTS: Workplace interventions, including discrete improvements
      in technology, work organization and ergonomics, and more comprehensive
      approaches can reduce levels of stress. In a few studies, these interventions
      have been associated with decreases in WRUED symptoms. Similar effects are noted
      in stress-related interventions targeting individuals before WRUEDs have
      appeared, and at several stages of these conditions. CONCLUSIONS: Health care
      providers can recognize stress-WRUED interactions through careful, directed
      inquiry. Both individual as well as workplace-targeted interventions, delivered
      in the primary care setting or workplace, may be helpful. Future research
      priorities include prospective studies of well-defined interventions, with ample
      measures of subject, intervention and workplace characteristics that can impact
      outcomes, and adequate follow-up to determine sustained effects.

PMID- 12071497
TI  - Environmental justice, local knowledge, and risk: the discourse of a community
      based cumulative exposure assessment.
AB  - While risk assessment continues to drive most environmental management decision
      making, its methods and assumptions have been criticized for, among other things,
      perpetuating environmental injustice. The justice challenges to risk assessment
      claim that the process ignores the unique and multiple hazards facing low-income
      and people of color communities and simultaneously excludes the local, non-expert
      knowledge which could help capture these unique hazards from the assessment
      discourse. This paper highlights some of these challenges to conventional risk
      assessment and suggests that traditional models of risk characterization will
      continue to ignore the environmental justice challenges until cumulative hazards
      and local knowledge are meaningfully brought into the assessment process. We ask
      whether a shift from risk to exposure assessment might enable environmental
      managers to respond to the environmental justice critiques. We review the US
      EPA's first community-based Cumulative Exposure Project, piloted in Brooklyn, NY,
      and highlight to what extent this process addressed the risk assessment critiques
      raised by environmental justice advocates. We suggest that a shift from risk to
      exposure assessment can provide an opportunity for local knowledge to both
      improve the technical assessment and its democratic nature and may ultimately
      allow environmental managers to better address environmental justice concerns in
      decision-making.

PMID- 12071498
TI  - Public support for ecosystem restoration in the Hudson River Valley, USA.
AB  - We applied the Theory of Planned Behavior to help understand the relationships
      between environmental beliefs, support for ecosystem restoration actions, and
      willingness to pay (WTP) for restoration and protection goals in the Hudson River
      estuary, New York State, USA. We conducted a mail survey with 3,000 randomly
      chosen local residents of the Hudson River estuary in the fall of 1999. As
      hypothesized, the broad ecosystem restoration goals of the Hudson River Estuary
      Action Plan were more strongly supported than the corresponding specific
      implementation actions. We found that beliefs and past behavior were better
      explanatory variables than sociodemographic characteristics for explaining
      people's support for ecosystem restoration actions and WTP for restoration and
      protection goals. Because ecosystem restoration goals appear to be more generally
      acceptable than specific restoration actions, proponents of restoration programs
      should not become complacent about the need for active public outreach and
      involvement even if initial restoration program discussions have been low in
      controversy. Efforts to assess and foster support for ecosystem restoration
      should be targeted toward audiences identified on the basis of beliefs and past
      behaviors rather than on sociodemographic characteristics.

PMID- 12071499
TI  - Post-project appraisals in adaptive management of river channel restoration.
AB  - Post-project appraisals (PPAs) can evaluate river restoration schemes in relation
      to their compliance with design, their short-term performance attainment, and
      their longer-term geomorphological compatibility with the catchment hydrology and
      sediment transport processes. PPAs provide the basis for communicating the
      results of one restoration scheme to another, thereby improving future
      restoration designs. They also supply essential performance feedback needed for
      adaptive management, in which management actions are treated as experiments. PPAs
      allow river restoration success to be defined both in terms of the scheme
      attaining its performance objectives and in providing a significant learning
      experience. Different levels of investment in PPA, in terms of pre-project data
      and follow-up information, bring with them different degrees of understanding and
      tbus different abilities to gauge both types of success. We present four case
      studies to illustrate how the commitment to PPA has determined the understanding
      achieved in each case. In Moore's Gulch (California, USA), understanding was
      severely constrained by the lack of pre-project data and post-implementation
      monitoring. Pre-project data existed for the Kitswell Brook (Hertfordshire, UK),
      but the monitoring consisted only of one site visit and thus the understanding
      achieved is related primarily to design compliance issues. The monitoring
      undertaken for Deep Run (Maryland, USA) and the River Idle (Nottinghamshire, UK)
      enabled some understanding of the short-term performance of each scheme. The
      transferable understanding gained from each case study is used to develop an
      illustrative five-fold classification of geomorphological PPAs (full, medium
      term, short-term, one-shot, and remains) according to their potential as learning
      experiences. The learning experience is central to adaptive management but rarely
      articulated in the literature. Here, we gauge the potential via superimposition
      onto a previous schematic representation of the adaptive management process by
      Haney and Power (1996). Using PPAs wisely can lead to cutting-edge, complex
      solutions to river restoration challenges.

PMID- 12071500
TI  - Procedures for ensuring community involvement in multijurisdictional river
      basins: a comparison of the Murray-Darling and Mekong river basins.
AB  - Community involvement is fundamental to the management of multijurisdictional
      river basins but, in practice, is very difficult to achieve. The Murray-Darling
      basin, in Australia, and the Mekong River basin in Southeast Asia are both
      cooperatively managed multijurisdictional river basins where the management
      authorities have expressed an aim of community involvement. In the Murray-Darling
      basin vigorous efforts have promoted a culture of community consultation
      throughout each of the state jurisdictions involved, although true participation
      has not necessarily been achieved. In the Mekong basin the community is much more
      diverse and the successes so far have been largely at the local level, involving
      action in subsections of the basin. These case studies suggest that community
      involvement in the form of community consultation across large
      multijurisdictional river basins is achievable, but more comprehensive
      participation is not necessarily possible.

PMID- 12071501
TI  - The effect of environmental conditions on the ability of a constructed wetland to
      disinfect municipal wastewaters.
AB  - Constructed wetlands are widely used all over the world for the treatment of
      municipal wastewaters, which are characterized by high concentrations of
      pathogens. The objectives of this study were (1) to study the effect of solar
      radiation and temperature on the ability of a constructed wetland to reduce the
      concentration of total coliforms (TC), and (2) to evaluate the relationship
      between the presence of Salmonella spp. in the outflow and the concentration of
      TC. The results of this study showed that under Mediterranean environmental
      conditions, the percentage reduction in coliforms was lower during winter
      compared to all other seasons. Maximum removal of coliforms was achieved under
      conditions of high solar radiation and temperature. In addition, solar radiation
      was found to play a greater role in coliform die-off at low temperatures than at
      high temperatures. Finally, it was found that the probability of Salmonella spp.
      appearance in the outflow of the wetland was related to the concentration of TC.
      The increase in coliform bacteria in the effluents also increased the chances of
      Salmonella appearance. The risk of Salmonella spp. appearance in the outflow is
      minimized when the concentration of TC is below 10(2)/100 mL.

PMID- 12071502
TI  - Macroinvertebrate and fish populations in a restored impounded salt marsh 21
      years after the reestablishment of tidal flooding.
AB  - During the last two decades, the State of Connecticut has restored tidal flow to
      many impounded salt marshes. One of the first of these and the one most
      extensively studied is Impoundment One in the Barn Island Wildlife Management
      Area in Stonington, Connecticut. In 1990, twelve years after the re-establishment
      of tidal flooding, the density of the marsh snail Melampus bidentatus, the
      numerically dominant macroinvertebrate of the high marsh, in Impoundment One was
      about half that in reference marshes below the breached impoundment dike. By 1999
      the densities of Melampus above and below the dike were not significantly
      different, but the shell-free biomass was greater above the dike as a result of
      the somewhat larger number and size of the snails there. Twenty-one years after
      the renewal of tidal flooding, three marsh macroinvertebrates (the amphipods
      Orchestia grillus and Uhlorchestia spartinophila and the mussel Geukensia
      demissa) were significantly less abundant in the previously impounded marsh than
      in the reference marshes, whereas another amphipod (Gammarus palustris) was more
      abundant above the breached dike where conditions appeared to be somewhat wetter.
      In 1991 the fish assemblage in a mosquito-control ditch in Impoundment One was
      similar to that in a ditch below the breached dike; however, the common mummichog
      Fundulus heteroclitus appeared to be less abundant in the restoring marsh. By
      1999 the number of mummichogs caught in ditches was significantly greater in
      Impoundment One than in the reference marsh, but the numbers of mummichogs
      trapped along the tidal creek were comparable above and below the dike. The
      results obtained in this study and those of other restoring marshes at Barn
      Island indicate the full recovery of certain animal populations following the
      reintroduction of tidal flow to impounded marshes may require up to two or more
      decades. Furthermore, not only do different species recover at different rates on
      a single marsh, but the time required for the recovery of a particular species
      may vary widely from marsh to marsh, often independently of other species.

PMID- 12071503
TI  - A GIS-based approach for assessing the regional conservation status of genetic
      diversity: an example from the southern Appalachians.
AB  - Conserving genetic diversity requires an assessment of the distribution of
      genetic variants in relation to patterns of land use and environmental variation
      at a regional scale. This assessment requires a novel approach to integrating and
      analyzing the genetic and environmental data across spatial scales. To explore
      the integration of genetic data with other geospatial data sets, we developed a
      GIS-based approach for examining patterns of genetic diversity for several
      species of salamanders in southern Appalachians. The genetic data, from allozyme
      surveys in the genetics literature, were integrated into a GIS database along
      with related attributes including population identifications and spatial
      locations. Using existing geospatial data, we classified sample locations as
      being either protected from anthropogenic disturbance (e.g., National Parks,
      Wilderness Areas) or as unprotected (e.g., private lands, multiple-use lands in
      National Forests). We used multidimensional scaling of allelic frequencies and
      contributions of populations to interpopulation differences in allelic richness
      to determine which populations had genetic characteristics most different from
      other populations in the sample. Measures of genetic differentiation were
      integrated into the GIS database to facilitate spatial analysis and visualization
      of the indices in relation to land use. This approach was useful for both
      identification of populations with components of genetic variation that were not
      well represented at protected sites and for identifying areas of species
      distributions where more genetic sampling would be necessary to make informed
      management decisions. Our approach could be readily adapted for use by managers
      and geneticists working with other species and types of genetic markers.

PMID- 12071504
TI  - Fuzzy assessment of land suitability for scientific research reserves.
AB  - Evaluating the characteristics of a set of sites as potential scientific research
      reserves is an example of land suitability assessment. Suitability in this case
      is based upon multiple criteria, many of which can be linguistically imprecise
      and often incompatible. Fuzzy logic is a useful method for characterizing
      imprecise suitability criteria and for combining criteria into an overall
      suitability rating. The Ecosystem Management Decision Support software combined a
      fuzzy logic knowledge base we developed to represent the assessment problem with
      a GIS database providing site-specific data for the assessment. Assessment of
      sites as a potential natural reserve for the new University of California campus
      at Merced demonstrates the benefits of fuzzy suitability assessment. The study
      was conducted in three stages of successively smaller assessment regions with
      increasingly fine spatial resolution and specificity of criteria. Several sites
      were identified that best satisfy the suitability criteria for a reserve to
      represent vernal pool habitat.

PMID- 12071505
TI  - Tijuana childhood lead risk assessment revisited: validating a GIS model with
      environmental data.
AB  - The objective of this research was to determine the spatial distributions of
      childhood lead poisoning and soil lead contamination in urban Tijuana. The Bocco
      Sanchez model of point-source emissions was evaluated in terms of validity and
      reliability. We compared the model's predicted vulnerable populations with
      observed cases of childhood lead poisoning in Tijuana, identified fixed point
      sources in the field, and analyzed 76 soil samples from 14 sites. The soil lead
      results were compared to the blood lead analyses performed on Tijuana children
      whose blood lead levels were > or =10 microg/dL, who reported that they did not
      use lead-glazed ceramics for cooking or storing food (n = 63). Using GIS,
      predicted vs observed risk areas were assessed by examining spatial patterns,
      including the distribution of cases per designated risk area. Chi-square analysis
      of expected vs observed values did not differ significantly at the p = 0.02
      level, showing that the model was strikingly accurate in predicting the
      distribution of subjects with elevated blood lead. Results reveal that while
      point sources are significant, other sources of lead exposure are also important.
      The relative public health risk from exposure to lead in an urban setting may be
      assessed by distinguishing among sources of exposure and associating
      concentrations to blood lead levels. The results represent an iterative approach
      in environmental health research by linking environmental and human biomarker
      lead concentrations and using these results to validate an environmental model of
      risk to lead exposure.

PMID- 12071506
TI  - Assessing vulnerability to invasion by nonnative plant species at multiple
      spatial scales.
AB  - Basic information on where nonnative plant species have successfully invaded is
      lacking. We assessed the vulnerability of 22 vegetation types (25 sets of four
      plots in nine study areas) to nonnative plant invasions in the north-central
      United States. In general, habitats with high native species richness were more
      heavily invaded than species-poor habitats, low-elevation areas were more invaded
      than high-elevation areas, and riparian zones were more invaded than nearby
      upland sites. For the 100 1000-m2 plots (across all vegetation types), 50% of the
      variation in nonnative species richness was explained by longitude, latitude,
      native plant species richness, soil total percentage nitrogen, and mean maximum
      July temperature (n = 100 plots; P < 0.001). At the vegetation-type scale (n = 25
      sets of four 1000-m2 plots/type), 64% of the variation in nonnative species
      richness was explained by native plant species richness, elevation, and October
      to June precipitation (P < 0.001). The foliar cover of nonnative species (log)
      was strongly positively correlated with the nonnative species richness at the
      plot scale (r = 0.77, P < 0.001) and vegetation-type scale (r = 0.83, P < 0.001).
      We concluded that, at the vegetation-type and regional scales in the north
      central United States, (1) vegetation types rich in native species are often
      highly vulnerable to invasion by nonnative plant species; (2) where several
      nonnative species become established, nonnative species cover can substantially
      increase; (3) the attributes that maintain high native plant species richness
      (high light, water, nitrogen, and temperatures) also help maintain nonnative
      plant species richness; and (4) more care must be taken to preserve native
      species diversity in highly vulnerable habitats.

PMID- 12071507
TI  - Public involvement in environmental assessment: the case of the nonparticipant.
AB  - Public involvement is recognized by legislators, practitioners, academics,
      nongovernment organizations and, most importantly, affected communities, as a
      fundamental component of environmental assessment (EA) processes. Experience with
      public involvement in EA has proven, however, that despite good intentions, there
      are formidable barriers to participation. This paper examines this issue, largely
      through a case study of a new Can$120 million hog processing facility in Brandon,
      Canada. Primary data were collected in three phases, using multiple
      methodological techniques, including document review, qualitative interviews, and
      a mail questionnaire. Results included a diverse list of barriers to involvement,
      grouped into two primary categories: structural and individual. A significant
      structural barrier was a belief that becoming involved would not make a
      difference as the ultimate decision in the case was a foregone conclusion. An
      important individual barrier was that people did not know about the EA. Finally,
      the results indicated that lack of interest was not an important reason for
      nonparticipation.

PMID- 12071508
TI  - Cell pathology in bipolar disorder.
AB  - OBJECTIVES: The objective of this paper is to review findings of morphometric
      postmortem studies conducted on tissues from subjects with bipolar disorder (BPD)
      to demonstrate that impairments of cell morphology and resilience may underlie
      the neurobiology of BPD. METHODS: Reports of alterations in number, density and
      size of neurons and glial cells in BPD are reviewed. Owing to the low number of
      postmortem studies on cellular pathology in BPD, abstracts of recent symposia are
      also discussed. RESULTS AND CONCLUSIONS: In BPD. significant reductions in the
      volume of several brain regions, as well as region- and layer-specific reductions
      in the number, density and/or size of neurons and glial cells have been
      demonstrated. Moreover, the results of recent clinical and preclinical studies
      investigating the molecular and cellular targets of mood stabilizing and
      antidepressant medications provide intriguing possibilities that impairments in
      neuroplasticity and cellular resilience may underlie the neurobiology of BPD.
      Future studies will likely examine the role of both genetic and environmental
      factors in the pathogenesis and cellular changes in BPD.

PMID- 12071509
TI  - Stress and depression: possible links to neuron death in the hippocampus.
AB  - Recent intriguing reports have shown an association between major depression and
      selective and persistent loss of hippocampal volume, prompting considerable
      speculation as to its underlying causes. In this paper we focus on the hypothesis
      that overt hippocampal neuron death could cause this loss and review current
      knowledge about how hippocampal neurons die during insults. We discuss (a) the
      trafficking of glutamate and calcium during insults; (b) oxygen radical
      generation and programmed cell death occurring during insults; (c) neuronal
      defenses against insults; (d) the role of energy availability in modulating the
      extent of neuron loss following such insults. The subtypes of depression
      associated with hippocampal atrophy typically involve significant hypersecretion
      of glucocorticoids, the adrenal steroids secreted during stress. These steroids
      have a variety of adverse affects, direct and indirect, in the hippocampus. Thus
      glucocorticoids may play a contributing role toward neuron death. We further
      discuss how glucocorticoids cause or exacerbate cellular changes associated with
      hippocampal neuron loss in the context of the events listed above.

PMID- 12071510
TI  - Neuroprotective effects of lithium in cultured cells and animal models of
      diseases.
AB  - Lithium, the major drug used to treat manic depressive illness, robustly protects
      cultured rat brain neurons from glutamate excitotoxicity mediated by N-methyl-D
      aspartate (NMDA) receptors. The lithium neuroprotection against glutamate
      excitotoxiciy is long-lasting, requires long-term pretreatment and occurs at
      therapeutic concentrations of this drug. The neuroprotective mcchanisms involve
      inactivation of NMDA receptors, decreased expression of pro-apoptotic proteins,
      p53 and Bax, enhanced expression of the cytoprotective protein, Bcl-2, and
      activation of the cell survival kinase, Akt. In addition, lithium pretreatment
      suppresses glutamate-induced loss of the activities of Akt, cyclic AMP-response
      element binding protein (CREB), c-Jun - N-terminal kinase (JNK) and p38 kinase.
      Lithium also reduces brain damage in animal models of neurodegenerative diseases
      in which excitotoxicity has been implicated. In the rat model of stroke using
      middle cerebral artery occlusion, lithium markedly reduces neurologic deficits
      and decreases brain infarct volume even when administered after the onset of
      ischemia. In a rat Huntington's disease model, lithium significantly reduces
      brain lesions resulting from intrastriatal infusion of quinolinic acid, an
      excitotoxin. Our results suggest that lithium might have utility in the treatment
      of neurodegenerative disorders in addition to its common use for the treatment of
      bipolar depressive patients.

PMID- 12071511
TI  - Glycogen synthase kinase-3beta, mood stabilizers, and neuroprotection.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a central component in many
      critical intracellular signaling mechanisms. These include the
      phosphatidylinositol 3-kinase/Akt cell survival pathway, which inhibits GSK-3beta
      activity. GSK-3beta itself inhibits the activation of several transcription
      factors, which are important cell survival factors, such as heat shock factor 1.
      These factors likely contribute to the recent revelation that GSK-3beta is a pro
      apoptotic enzyme. Recently, lithium has been identified as a selective and direct
      inhibitor of GSK-3beta. Based on these findings, we have proposed that part of
      the neuroprotectant properties of lithium is due to its ability to inhibit GSK
      3beta, and thus block the facilitation of apoptosis produced by GSK-3beta. Since
      several anticonvulsants recently have been shown to be effective mood
      stabilizers, we examined if these agents are capable of protecting cells from GSK
      3beta-facilitated apoptosis. In addition to lithium, both valproic acid and
      lamotrigine, but not carbamazepine, provided protection from GSK-3beta
      facilitated apoptosis in human neuroblastoma SH-SY5Y cells. These results
      demonstrate that several drugs therapeutic for bipolar disorder can provide
      neuroprotection by inhibiting the pro-apoptotic effects of GSK-3beta, providing
      new evidence that dysregulation of GSK-3beta may contribute to the
      pathophysiology of bipolar disorder.

PMID- 12071512
TI  - Regulation of ER stress proteins by valproate: therapeutic implications.
AB  - OBJECTIVES: This paper reviews results of our studies examining the regulation of
      endoplasmic reticulum (ER) stress proteins by valproate (VPA). and discusses the
      possible implications in bipolar disorder. METHODS: Our previous studies in the
      field are reviewed along with relevant literature. RESULTS: Using differential
      display PCR, we identified GRP78 as a VPA-regulated gene in rat cerebral cortex.
      We also showed that other members of the ER stress proteins family, GRP94 and
      calreticulin, are also upregulated by VPA. Immunohistochemistry identified that
      ER stress proteins are increased in frontal and parietal cortex, as well as
      regions of the hippocampus in rat brain following chronic treatment with VPA.
      CONCLUSIONS: Regulation of ER stress proteins by VPA may prove to be important to
      the mechanism of action of the drug. The neuroprotective role of these proteins
      may also prove to be involved in the pathophysiology of bipolar disorder.

PMID- 12071513
TI  - Volumetric MRI studies of mood disorders: do they distinguish unipolar and
      bipolar disorder?
AB  - The authors reviewed magnetic resonance imaging volumetric imaging results in
      major mood disorders, particularly comparing similarities and differences from
      studies of bipolar disorder and unipolar major depression. Abnormalities of
      cerebral brain regions appear inconsistently in mood disorders and, when present,
      typically consist of decreased frontal or prefrontal cortical volumes in both
      unipolar depression and bipolar disorder. In contrast, subcortical and medial
      temporal abnormalities are more commonly observed and are different between these
      two major classes of affective illness. Specifically, whereas structural
      enlargement of the basal ganglia and amygdala have been observed in bipolar
      disorder, in unipolar depression, these structures appear to be smaller in
      patients than healthy subjects. These findings suggest that affective illnesses
      may share in common an underdeveloped or atrophied prefrontal region, leading to
      loss of cortical modulation of limbic emotional networks. The effect of this loss
      results in unipolar depression or cycling (mania with depression) depending on
      the abnormalities of the subcortical structures involved. The cerebellum may also
      play a role in the presentation of mood disorders. This hypothesis remains
      speculative as much more research is needed to specifically examine how
      morphometric brain abnormalities translate into the neurophysiologic deficits
      that produce mood disorders.

PMID- 12071514
TI  - Volumetric brain imaging findings in mood disorders.
AB  - Volumetric neuroimaging is increasingly being used by researchers of affective
      disorders to assess potential involvement of different brain structures in mood
      regulation and to test neuroanatomic models of mood disorders. In unipolar
      depression, findings suggest abnormalities in the frontal lobe (particularly the
      subgenual prefrontal cortex), basal ganglia (particularly the caudate and
      putamen), cerebellum, and hippocampus/amygdala complex. In bipolar disorder,
      abnormalities in the third ventricle, frontal lobe, cerebellum, and possibly the
      temporal lobe are noted. We review the findings for the various regions of the
      brain, and discuss the implications on the understanding of mood disorders.
      Directions for future research in volumetric imaging is then discussed.

PMID- 12071515
TI  - Evaluation of sialyl Lewis(a), sialyl Lewis(x), and sialyl Tn antigens expression
      levels as predictors of recurrence after curative surgery in node-negative
      colorectal cancer patients.
AB  - This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x
      )(Le(x)), or sialyl Tn antigen expression could identify a subset of node
      negative colorectal cancer patients that are at high risk for recurrence after
      curative surgery. Tumor tissue samples from 90 patients with node-negative
      colorectal cancer, who had undergone surgical resection, were analyzed
      immunohistochemically for the expression of each antigen. Patients were
      classified as having low or high antigen expression depending on whether more or
      less than 40% of the field showed positive staining. The main outcome measure for
      each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl
      Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas,
      respectively. The median follow-up was 83.5 months. Patients with high sialyl
      Le(x) expression had shorter disease-free intervals than those with low sialyl
      Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn
      antigens did not show a significant relationship with disease-free survival.
      Cox's regression analysis revealed that sialyl Le(x) expression was an
      independent predictor for disease-free survival, separate from T factor or tumor
      location. High sialyl Le(x) expression may be useful in identifying a subset of
      node-negative colorectal cancer patients who are at high risk for recurrence.

PMID- 12071516
TI  - Effect of Withania somnifera on CTL activity.
AB  - The stimulatory effect of Withania somnifera on cytotoxic T lymphocytes was
      determined in Balb/C mice by the Winn's Neutralization assay using CTL sensitive
      EL4 thymoma cells as target cells. Withania somnifera showed a significant
      increase in CTL production both in vivo as well as in vitro. The survival time of
      E14 cells alone in treated animals was only 21 days and in the Withania extract
      treated group was 45 days with a percentage increase in life span (% ILS) of
      114.28%. The survival rate of animals administered with EL4 cells (target) which
      were incubated with alloimmunized spleen cells (effector) from normal Balb/c mice
      was 33 days (% ILS 57.14%) and when this group was treated with Withania extract
      (20 mg/dose/animal i.p. for 10 days) their life span was increased to 53 days (%
      ILS 152.38%). The survival days of animals after the administration of EL4 cells
      incubated with alloimmunized spleen cells (effector) from Withania treated
      animals was 48 days (% ILS 118.18%) and when these animals continued with the
      Withania treatment their life span increased to 61 days (%ILS 177.27%). There was
      a significant increase in life span when animals were treated with EL4 cells
      incubated with effector cells generated by mixed lymphocyte culture of Balb/c
      mice and C57BL/6 mice in the presence (172.73%) and absence of Withania extract
      (59.09%). These studies indicate that Withania somnifera could stimulate the
      generation of cytotoxic T lymphocyte and it may reduce tumour growth.

PMID- 12071517
TI  - Genetic polymorphisms of cytochrome P450 1A1 and risk of gallbladder cancer.
AB  - The relation between cytochrome P4501A1 (CYP1A1) gene polymorphisms and the risk
      of gallbladder cancer was examined. To clarify individual differences in
      susceptibility to gallbladder carcinogenesis, we investigated the frequency of
      the Mspl and Ile-Val polymorphisms of the CYP1A1 gene, in 52 patients with
      gallbladder cancer (32 females, 20 males) and 104 healthy controls (64 females,
      40 males). We then examined the relationship between the CYP1A1 polymorphisms and
      the development of gallbladder cancer in members of both sexes. A statistical
      difference in the frequencies of the MspI and Ile-Val polymorphisms or their
      alleles (ml, m2 and Ile, Val) was not observed in the male patients and controls.
      Among females, however, the frequencies of genotypes C and Ile/Val were
      significantly higher (p < 0.05) in the patients than in their controls. Moreover,
      the frequency of the hetero genotype Ile/Val was statistically higher (p < 0.05)
      in the female patients than in the male patients. This study demonstrated a
      significant over-representation of genotypes C and Ile/Val in female patients
      with gallbladder cancer. Females with genotypes C and/or Ile/Val may have a high
      genetic susceptibility to the development of gallbladder cancer.

PMID- 12071518
TI  - Clinical significance of vascular endothelial growth factor expression in gastric
      cancer.
AB  - Vascular endothelial growth factor (VEGF) is an angiogenic factor in human cancer
      tissue. To clarify the clinical significance of this factor, we investigated the
      VEGF expression in early and advanced gastric cancer. This study included
      analysis of data on 243 patients with gastric cancer, including 118 in the early
      stage and 125 in the advanced stage. VEGF was immunohistochemically stained. Of
      243 tumors, 102 (42%) were VEGF-positive. The VEGF-positive gastric cancers were
      larger, more invasive, and classified in the more advanced stage than VEGF
      negative ones. Patients with VEGF-positive cancers had significantly lower
      survival rates than did those with negative ones, both in early and advanced
      stages (P < 0.05, P < 0.01, respectively). The VEGF-positive isolates had more
      hematogenous metastases than VEGF-negative ones. Multivariate analysis revealed
      VEGF to be an independent prognostic factor and independent risk factor for liver
      metastasis. The VEGF expression in cancer cells can serve as a pertinent
      prognostic indicator both in early and advanced gastric cancer.

PMID- 12071519
TI  - Preferential transcription of a gene for alpha amylase in the carcinoid tumor of
      African rodent Mastomys natalensis.
AB  - The carcinoid tumor in Mastomys natalensis provides a useful animal model of
      tumorigenesis. We investigated preferentially transcribed genes in this carcinoid
      tumor by differential hybridization. Fourteen clones corresponding to high levels
      of transcription were isolated from a cDNA library. Sequencing analysis and a
      homology search revealed that the clones corresponded to genes for chromogranin
      and alpha-amylase. High-level transcription of a gene for alpha-amylase gene in
      Mastomys carcinoid tumor was confirmed by Northern blotting analysis.
      Furthermore, Western blotting analysis confirmed the expression of alpha-amylase
      in tumors at the protein level. Immunohistochemical staining revealed alpha
      amylase in the cytoplasm of Mastomys carcinoid tumors. Our results demonstrated
      that an exocrine enzyme 'amylase' could be produced ectopically by a neuroen
      docrine tumor.

PMID- 12071520
TI  - A long-standing cystic lymph-node metastasis from occult thyroid carcinoma.
AB  - Here we report the case of a patient with a soft tissue mass of the neck. For
      more than 10 years it was thought to be a branchial cyst and was later diagnosed
      to be a cystic lymph node metastasis from an occult thyroid carcinoma.

PMID- 12071521
TI  - Solitary bone plasmacytoma in a young patient.
AB  - Plasma cell disorder, a disease of the elderly, is extremely rare in those below
      30 years of age. A young 18 year old patient with solitary plasmacytoma is
      described in this case report.

PMID- 12071522
TI  - Familial asynchronous bilateral primary male breast carcinoma.

PMID- 12071523
TI  - Transhiatal surgical resection for adenocarcinoma of the cardia.
AB  - Aim of this study is to define feasibility and effectiveness of the transhiatal
      esophagogastric resection in cardia adenocarcinoma. From 1981 to 2001, we
      submitted to surgery 85 patients affected by cardia adenocarcinoma. Since 1994,
      34 patients, in consideration of clinical, anatomosurgical (Siewert II-III) and
      pathologic (T1-3, cN mediastinal negative) findings, underwent transhiatal
      esophagogastric resection according to Pinotti's technique. This consisted in the
      midline opening of the central tendon of the diaphragm, ligature and section of
      the left inferior phrenic vessels, exposure and anterior retraction of the
      pericardium. The approach allowed in all cases a satisfactory esophageal
      mobilization and a good dissection of the inferior mediastinal structures
      avoiding thoracotomy. Postoperative complications were observed in 8 patients
      (24%). In 4 cases the complications were medical (11.8%) and in 4 cases surgical
      (11.8%). Death occurred in 4 cases (11.8%): in 3 patients (8.8%) for local
      complications (2 anastomotic leaks and 1 hemorrage) and in 1 (2.9%) for cardiac
      failure. The 26 non complicated cases had an uneventful postoperative course and
      were discharged 12 days after surgery. Middle and long term results were
      evaluated in terms of locoregional recurrence rate and actuarial survival. At 1
      and 2 years locoregional recurrence occurred in 8.8% and 11.8% of cases
      respectively. Five-year overall survival was 22.5%. In selected cases (Siewert
      type II-III, T1-3 tumors with clinically negative mediastinal lymphnodes) the
      procedure in study appears technically feasible, it provides a satisfactory
      volume of esophageal exeresis and an adequate extension of mediastinal
      lymphadenectomy, representing a safe and effective alternative to thoracotomy in
      cardia cancer surgery.

PMID- 12071524
TI  - beta-Catenin alteration in cancer of the ampulla of Vater.
AB  - To investigate the contribution of beta-catenin to the development of carcinoma
      of the ampulla of Vater, genetic alterations of beta-catenin gene, CTNNB-1 were
      searched. Mutational analysis of exon3 in CTNNB-1, which encodes the
      serine/threonine residues for GSK-3beta phosphorylation sites, was performed on
      21 cases of carcinoma of the ampulla of Vater, by means of polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) followed by
      nucleotide sequencing. We found one deleted mutation at codon 32 to approximately
      65 in one case of carcinoma of the ampulla of Vater. We also analyzed subcellular
      localization of beta-catenin protein in all cases immunohistochemically, and
      confirmed its accumulation in the nucleus in four cases including in a CTNNB-1
      mutated one. This is the first study to show CTNNB-1 mutation and beta-catenin
      expression in carcinoma of the ampulla of Vater. These results suggested that
      abnormal Wnt-wingless signaling and in particular beta-catenin alteration caused
      accumulation of beta-catenin, which might partially contribute to the development
      of carcinoma of the ampulla of Vater.

PMID- 12071525
TI  - Is suprahyoid dissection a diagnostic operation in lower lip carcinoma?
AB  - Carcinoma of the lower lip can be treated primarily by surgical procedures. One
      of the most prominent characteristics of the tumor is that it can metastasize to
      submental and submandibular lymph nodes. For that reason, bilateral suprahyoid
      dissection with surgical treatment of the primary lesion is a diagnostic approach
      for some investigators and therapeutic for others. We evaluated whether bilateral
      suprahyoid dissection is a diagnostic approach in lower lip cancer or not.
      Prophylactic suprahyoid dissection had been performed in 53 patients who had been
      operated for squamous cell carcinoma of the lower lip in Ankara Oncology
      Hospital. Four of the cases were female and 49 male. The median age was 62. Forty
      five out of 53 cases had T2 lesions and in the remaining 8 had T3 lesions. All
      patients were clinically node negative. In the dissection material, lymph node
      metastasis were present in 8 out of the 45 cases who had T2 tumors (17,7 %) and
      in 2 out of the 8 cases who had T3 tumors (25%). Three of the 10 cases who had
      regional lymph node metastasis underwent radiotherapy after surgery. Seven of
      them did not receive radiotherapy. Thirty-nine patients had regular follow-up for
      a median of 4.5 years. During this period, none of the patients had regional
      recurrence in cervical lymph nodes. According to these data, we conclude that
      bilateral suprahyoid dissection is both a diagnostic and a therapeutic approach
      in T2, T3 and clinically N0 lower lip tumors.

PMID- 12071526
TI  - Microsatellite alterations in non-small cell lung cancer.
AB  - Genetic alterations at 12 dinucleotide repeat loci located on human chromosomes
      2, 3, 12, and 17 have been analyzed in non-small cell lung cancer from Thai
      patients. Seventeen out of 30 cases (57%) harbored the microsatellite
      alterations. Of the 30 cases, 19 patients had a history of tobacco smoking, of
      whom 14 (74%) were in the group with microsatellite alterations, whereas 3 out of
      11 non-smokers (26%) had these alterations. The frequency of microsatellite
      alterations among smokers was significantly higher than it was in non-smokers (P
      = 0.01 Fisher's exact test; odds ratio; 7.47).

PMID- 12071527
TI  - Indication of hysteroscopy in tamoxifen treated breast cancer patients.
AB  - The aim of this study was to indicate the patients treated with tamoxifen for
      breast cancer in which hysteroscopy with biopsy should be considered mandatory.
      414 breast cancer patients who underwent hysteroscopy with bioptic evaluation
      were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen
      daily as adjuvant therapy for six up to a hundred months. Of the remaining 80
      control patients, which had not received tamoxifen, 30 were in premenopause
      (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients
      were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal
      (Group IIB = 262 patients) groups. All patients were further classified in
      asymptomatic or symptomatic groups considering whether uterine bleeding was
      absent or present. The evaluation of the endometrial mucosa was performed by
      office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant
      lesions were found in 7.8% of the cases. The incidence of premalignant and
      malignant lesions in IIB patients treated for longer than 3 years (11.7%) was
      higher than that observed in IIB patients treated for less than 3 years (1.3%).
      There was a significant difference in terms of endometrial pathology between
      Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%)
      and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no
      cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women,
      2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of
      endometrial cancer were observed in Group IIB and had a diagnosis of poor
      prognosis. In conclusion the hysteroscopy with biopsy should be considered the
      first diagnostic procedure to perform in tamoxifen-treated postmenopausal
      patients presenting uterine bleeding and in postmenopausal women treated for
      longer than 3 years. In premenopause, hysteroscopy should be proposed to women
      with ultrasonographic abnormalities and/or with uterine bleeding to patients at
      high risk for endometrial cancer.

PMID- 12071528
TI  - Non-small-cell lung cancer with nonfamilial diffuse palmoplantar keratoderma.
AB  - Palmoplantar keratoderma (PPK) is a congenital or acquired disorder characterized
      by the abnormal thickening of the skin of the palms and soles. The thickening can
      present as a diffuse, focal or punctate pattern. It has been reported to be
      associated with internal malignancies such as lung and esophageal carcinomas.
      When PPK is associated with malignancy the prognosis is poor. Patients with these
      conditions should undergo frequent medical examinations, which should include
      chest radiography and cytologic examination of the sputum. The present patient is
      a 47-year-old-man with PPK who suffered from metastatic non-small-cell carcinoma
      of the lung.

PMID- 12071529
TI  - Diagnostic approach of effusion cytology using computerized image analysis.
AB  - The objective of this study is to investigate whether image cytometry is a
      sensitive and specific method for the differential diagnosis of equivocal cells
      in routine cytology of effusion smears. One hundred four effusion smears were
      studied from routine cytologic material. Cytologically 56 (53.8%) of the smears
      were classified as malignant, 26 (24%) as suspicious and 22 (21.1%) as benign.
      Two morphometric variables (nuclear major axis length and nuclear area) of the
      nuclei were measured by an image analysis system. Higher values for the area were
      found for malignant rather than benign and suspicious cells (p < 0.0005 and p <
      0.005 respectively). The same result was extracted for the nuclear major axis
      length values (p < 0.0005 and p < 0.0005 respectively). Values of nuclear major
      axis length and nuclear area didn't differ significantly between benign and
      suspicious cells (p = 0.071 and p = 0.066 respectively). The results show that
      the range of the values for suspicious cells is closer to the range of the benign
      cells. Cytomorphometry of the effusion smear cells may provide important
      information for the differentiation of atypical mesothelial cells from malignant
      adenocarcinoma cells.

PMID- 12071530
TI  - Laryngeal endocrinomas (carcinoids and relevant neoplasms): analysis of 278
      reported cases.
AB  - This study was carried out to provide extensive information obtained from
      statistical analysis of laryngeal endocrinomas for the use of investigators
      working in this particular research field. A total of 278 patients with both
      typical and atypical varieties of carcinoids, and with small/oat cell carcinomas
      (SCC/OCC) exhibiting a confirmed endocrine nature were statistically evaluated,
      and the significance in various clinicopathologic aspects among these three types
      of such endocrine neoplasms of the larynx was compared. A statistically
      significant difference between two groups of typical carcinoid and atypical
      variety was evident only in a few items such as rates of metastases, positive
      CEA, and multisecretory activity, while a significant difference between the
      carcinoid groups and SCC/OCC group was demonstrated in numerous areas, among
      others, e.g. 1) in the overall rates of metastases and at the sites of
      involvement, 2) in Grimelius argyrophilia, 3) in immunohistochemical
      demonstration of positive chromogranin, CEA, calcitonin and multisecretory
      activity, and 4) in the 5-year survival rates. Such a definite difference between
      the carcinoid groups and SCC/OCC group suggested an apparently different
      characteristic nature present between these two series of neoplasms. The
      necessity of an international agreement regarding diagnostic criteria for typical
      carcinoids and atypical varieties was in particular emphasized from a viewpoint
      of an exceptionally high incidence of laryngeal atypical carcinoids in comparison
      to such neoplasms in other organs.

PMID- 12071531
TI  - Correlation of tumor growth index with early treatment response in cervical
      carcinoma.
AB  - Despite the recent progress in the management of cervical carcinoma, treatment
      failure is quite common and therefore it is necessary to identify predicting
      factors for tumor response. It is known that both cell proliferation and
      apoptosis determine the tumor growth index (TGI) which reflects the overall
      contribution of gene defects. Here we explored whether the TGI index could be a
      better predictor of response in comparison to cell proliferation or apoptosis as
      separate phenomena. Twenty-five patients with cervical carcinoma treated with
      radiation alone or neoadjuvant chemotherapy plus surgery were analyzed. Cell
      proliferation and apoptosis determined by PCNA immunohistochemical expression and
      tumor nucleosomes by ELISA, respectively, were used to calculate the TGI, which
      was analyzed with regard to early tumor response. Our results show that most
      patients with a negative TGI had early response suggesting increased tumor
      sensitivity(p = 0.0186). On the other hand, patients with a positive TGI were
      more resistant to treatment. TGI was not related to age, clinical stage or tumor
      size. In conclusion, the results of this study show that the determination of the
      TGI, but no cell proliferation or apoptosis, as separate events, is able to
      predict an early treatment response to either radiation or chemotherapy in
      cervical carcinoma.

PMID- 12071533
TI  - Contribution of HPLC mass screening for neuroblastoma to a decrease in mortality.
AB  - The aim of this study is the estimation of the contribution of HPLC mass
      screening for neuroblastoma to the decrease in deaths due to this disease. The
      mortality rates of malignant neoplasms of the adrenal glands (ICD 9, 1940; ICD
      10, C74; virtually all the cases of these codes are neuroblastoma during
      childhood) at 1-4 years of age in cohorts born in 1979-1984, 1985-1988, and 1989
      1992 in the whole of Japan were calculated, using data obtained from the Ministry
      of Health and Welfare. The numbers of infants screened by HPLC in the cohorts
      were estimated through the reports of the Ministry of Health and Welfare and the
      database of the Japanese Society for Mass-screening. The mortality of the cohort
      born in 1989-1992, in which 77.8% of the live births were screened by HPLC, was
      1.73 per 100,000 live births. This is about half of that (3.26) of the cohort
      born in 1979-1984, in which few infants were screened. On the assumption that
      cases of the 1985-1988 and 1989-1992 cohorts died according to the mortality rate
      of the 1979-1984 cohort, the expected numbers of deaths were estimated; that for
      the 1985-1988 cohort was 178.51 (of them, that for the infants screened by HPLC
      was 39.65), and that for the 1989-1992 cohort was 159.78 (of them, that for the
      infants screened by HPLC was 124.33). The observed numbers of deaths were 145 and
      85, respectively. Assuming that non-HPLC methods have no effects and using 2
      unknown quantities x (contribution of HPLC) and y (other factors), simultaneous
      equations (1) 178.51 - 39.65x - 178.51y = 145 and (2) 159.78 - 124.33x - 159.78y
      = 85 were made. Solving them, x = 0.5041 and y = 0.0757 were obtained. In
      conclusion HPLC screening targeting infants aged 6 months reduces death of
      adrenal neuroblastomas at 1-4 years of age by about 50%.

PMID- 12071532
TI  - Re-expression of the cadherin-catenin complex in lymph nodes with metastasis in
      advanced gastric cancer: the relationship with patient survival.
AB  - The cadherin-catenin complex has been recognized as an important factor
      associated with tumor metastasis. However, the clinical significance of the
      expression of adhesion molecules in lymph nodes with metastasis remains unclear.
      The aim of this study was to investigate the clinical significance of the re
      expression of the cadherin-catenin complex in metastatic lymph nodes in patients
      with advanced gastric cancer. Immunohistochemical expression of E-cadherin, alpha
      and beta-catenin were analyzed in 96 primary gastric cancers with serosal
      invasion and in 79 lymph nodes with metastasis. The expression levels of these
      adhesion molecules in primary tumors and lymph nodes with metastasis were
      compared. Ninety-four out of 96 primary tumors (98%) showed reduced expression of
      adhesion molecules. Out of 79 cases with lymph node metastasis, increased
      expression of one or more adhesion molecules in metastatic foci as compared with
      primary tumors was detected in 52 cases (66%). Re-expression of adhesion
      molecules in metastatic lymph nodes was detected in a more advanced stage. The
      overall 5-year survival rate of the 52 patients who had lymph nodes with
      metastasis with re-expression of adhesion molecules (8%) was significantly poorer
      than that of the 27 who had lymph nodes with metastasis without re-expression of
      adhesion molecules (33%, P = 0.0012). The re-expression of the cadherin-catenin
      complex in lymph nodes with metastasis may play an important role in the growth
      of cancer cells in metastatic foci. A comparison of the expression patterns of
      adhesion molecules between the primary tumor and metastatic lymph nodes may
      provide new prognostic information for patients with advanced gastric cancer.

PMID- 12071534
TI  - Multifactorial analysis of survival and recurrences in differentiated thyroid
      cancer. Comparative evaluation of usefulness of AGES, MACIS, and risk group
      scores in Mexican population.
AB  - Many risk factors have been identified in differentiated thyroid cancer, with
      them, some prognostic scores have been designed to asign the risk of recurrence
      and survival. In Mexican population, this type of study is scarce. This is a
      retrospective review of 180 patients with differentiated thyroid cancer
      completely treated at the Hospital de Oncologia, IMSS, in Mexico City from 1980
      to 1990. All prognostic factors were analyzed and a score obtained either by the
      method of AGES, MACIS, or SKMH. Correlation of recurrences and survival was
      carried out according to score or risk assignment. There was a predominance of
      females (4.8:1), 48% had metastatic cervical nodes, median tumor size was 4 cm,
      16% had multiple macroscopic thyroid tumors, in 12% resection was incomplete, 96%
      were papillary, and 4% follicular cancers. According to AGES, 46% were high risk
      patients, 49.4% with MACIS and 45.5% with SKMH, respectively. Median follow-up
      was 8.3 years. There were 67 (37%) recurrences. Ten-year overall survival was
      89.4% and disease-free survival was 79.2%. There was no statistical significant
      difference of survival of AGES until the score reached 6 or more or the MACIS
      score reached 8 or more. Cox multivariate model showed that above the age of 45,
      tumor size of 5 cm or more, follicular histology, multiple macroscopic thyroid
      tumors, and extracapsular node invasion affected ten-year survival. In
      conclusions our patients are diagnosed at more advanced stages than patients in
      the U.S. or European countries. Nearly one half of our patients belonged to the
      high-risk group. This study confirms that patients over the age of 45, tumor size
      > 5 cm, and follicular histology are adverse prognostic factors and report that
      extracapsular node invasion and multiple macroscopic thyroid tumors are also
      adverse prognostic factors. In Mexican population, with 50% of high-risk
      patients, AGES and MACIS scores reached statistical differences with higher
      qualifications than observed in the U.S.

PMID- 12071535
TI  - Evaluation of naphthal-NU, a 2-chloroethylnitrosourea derivative of
      naphthalimide, as a mixed-function anticancer agent.
AB  - Naphthal-NU, 2-[2-[3-(2-chloroethyl)-3-nitrosoureido]ethyl]-1H
      benz[de]isoquinoline-1,3-dione (Compound 1) has been synthesized as a rationally
      designed new mixed-function anticancer agent from 1,8-naphthalic anhydride. Its
      chemical alkylating activity compared with CCNU as standard compound indicated
      that it possesses greater alkylating activity than the latter. Its antitumour
      efficacy was assessed in vivo in two murine ascites tumours namely Sarcoma-180 (S
      180) and Ehrlich ascites carcinoma (EAC) by measuring the increase in median
      survival times (MST) of drug treated (T) over untreated control (C) mice. Three
      clinical drugs namely CCNU (lomustine), endoxan (cyclophosphamide) and 5
      fluorouracil (5-FU) were used as positive controls for comparison. Compound 1 has
      displayed excellent and reproducible antitumoural activity having curative
      effects in these tumours comparable with CCNU and 5-FU. It has also significantly
      increased the life span of mice bearing highly advanced tumour for 10 days before
      the drug challenge. Its toxicity was also assessed in vivo in normal and in S-180
      bearing mice by measuring drug-induced changes in hematological parameters,
      femoral bone marrow and splenic cellularity sequentially on days 9, 15 and 21
      following drug treatment at the optimum dose of 50 mg/kg from day 1 to 7. The
      results indicated that the compound did not adversely affect hematopoiesis. Drug
      induced hepatotoxicity and nephrotoxicity were also evaluated at its optimum dose
      on those days but no such toxicities were detected. It was further screened in
      vitro in 6 different human tumour cell lines but no significant activity was
      observed in those lines.

PMID- 12071536
TI  - Sheep form of leucocyte function antigen-3 (T11TS) exerts immunostimulatory and
      anti-tumor activity against experimental brain tumor. A new approach to
      biological response modifier therapy.
AB  - In order to establish the mechanism(s) of immunomodulatory and anti-tumor
      properties of sheep erythrocytes (SRBC), the T11 target structure (T11TS) or CD58
      molecule as a pertinent component of SRBC was isolated, purified and finally
      administered in rats with experimentally induced brain tumor. Results showed
      inhibition and/or abrogation of tumor growth. Subsequent studies on cellular
      immunity also revealed potentiation of lymphocytes and PMNs at peripheral level.
      Presence of activated lymphocytes as revealed through flowcytometric analysis of
      CD25 expression evidenced infiltration of activated lymphocytes in the brain
      tumor tissues. The analysis of data suggests that T11TS or sheep form of LFA3 is
      capable of inhibiting/preventing tumor growth in rat brain by way of
      immunopotentiation (CMI) at the peripheral immune system and thereby facilitating
      infiltration of the activated lymphocytes into the brain cavity through the blood
      brain barrier.

PMID- 12071537
TI  - Incidence of sleep apnea in a presumably healthy working population: a
      significant relationship with excessive daytime sleepiness.
AB  - Seventy-eight workers, drawn from a population of 1502 presumably healthy working
      men who were interviewed about sleep habits and sleep disorders, underwent
      polygraphic recordings for at least 1 night. A significant association was found
      between the complaint of excessive daytime sleepiness and the incidence of sleep
      apnea. Workers with more than 10 apneas per hour of sleep complained
      significantly more about loud snoring, hypermotility in sleep, and frequent
      headaches. They had significantly more ENT findings and hypertension.

PMID- 12071538
TI  - Sleep apnea in the presumably healthy working population--revisited.

PMID- 12071539
TI  - Functional role for cannabinoids in respiratory stability during sleep.
AB  - STUDY OBJECTIVES: Serotonin, acting in the peripheral nervous system, can
      exacerbate sleep-related apnea, and systemically administered serotonin
      antagonists reduce sleep-disordered respiration in rats and bulldogs. Because
      cannabinoid receptor agonists are known to inhibit the excitatory effects of
      serotonin on nodose ganglion cells, we examined the effects of endogenous
      (oleamide) and exogenous (delta9-tetrahydrocannabinol; delta9THC) cannabimimetic
      agents on sleep-related apnea. DESIGN: Sleep architecture, respiratory pattern,
      and apnea expression in rats were assessed by polysomnography. A repeated
      measures, within-subjects, fully nested crossover design was used in which each
      animal was recorded on exactly 12 occasions. PARTICIPANTS: Eleven adult male
      Sprague-Dawley rats were instrumented for chronic polysomnography. INTERVENTIONS:
      Animals were recorded following intraperitoneal injection of various doses of
      delta9THC, oleamide, and serotonin, alone and in combination. MEASUREMENTS AND
      RESULTS: Our data show that delta9THC and oleamide each stabilized respiration
      during all sleep stages. With delta9THC, apnea index decreased by 42% (F=2.63;
      p=0.04) and 58% (F=2.68; p=0.04) in NREM and REM sleep, respectively. Oleamide
      produced equivalent apnea suppression. This observation suggests an important
      role for endocannabinoids in maintaining autonomic stability during sleep.
      Oleamide and delta9THC blocked serotonin-induced exacerbation of sleep apnea
      (p<0.05 for each), suggesting that inhibitory coupling between cannabinoids and
      serotonin receptors in the peripheral nervous system may act on apnea expression.
      CONCLUSIONS: This study demonstrates potent suppression of sleep-related apnea by
      both exogenous and endogenous cannabinoids. These findings are of relevance to
      the pathogenesis and pharmacological treatment of sleep-related breathing
      disorders.

PMID- 12071540
TI  - "Functional role for cannabinoids in respiratory stability during sleep" by D.W.
      Carley, et al.

PMID- 12071541
TI  - Procedural skill learning in obstructive sleep apnea syndrome.
AB  - STUDY OBJECTIVES: To better characterize the cognitive deficits observed in
      obstructive sleep apnea syndrome (OSAS) by examining procedural skill learning
      abilities. DESIGN: Procedural skill learning was assessed using Mirror Tracing
      and Rotary Pursuit skill learning tasks. Subjects also completed a comprehensive
      neuropsychological test battery. SETTING: Cognitive testing was performed during
      the day following the second of two consecutive nights during which sleep and
      respiratory variables were recorded. PARTICIPANTS: Two groups (28 OSAS patients
      and 18 normal controls) with equivalent mean age and education levels.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: No significant differences in
      learning rates were observed between the groups on the Rotary Pursuit Task. On
      the Mirror Tracing Task, overall learning of the skill and transfer to a new
      figure or to the reverse tracing direction was similar in the OSAS and NC groups.
      However, there was a subgroup of OSAS subjects (n=11) who showed marked
      difficulties in the initial acquisition of the Mirror Tracing Task. This
      subgroup's performance was no longer significantly different from that of
      controls and OSAS subjects without initial adaptation difficulty in the
      subsequent trials. Performance of subjects who had difficulty with initial
      adaptation on the Mirror Tracing was also significantly lower on tests of frontal
      executive function, but not on episodic memory tests. Sleep and respiratory
      variables did not distinguish between the two subgroups of OSAS patients.
      However, none of the young OSAS subjects (<40 years) presented this deficit.
      CONCLUSION: Results indicate that contrary to this study's hypothesis, OSAS
      patients did not show procedural skill learning deficits. A subgroup of OSAS
      patients, however, did show deficits in initial skill adaptation and difficulties
      on other neuropsychological tests. Frontal dysfunction and decrement in
      psychomotor efficiency and vigilance appeared to be the most consistent
      explanation for characterizing the profile of neuropsychological test results
      among the OSAS patients.

PMID- 12071542
TI  - Gender and obstructive sleep apnea syndrome, part 1: Clinical features.
AB  - In the two decades after obstructive sleep apnea syndrome (OSAS) was described,
      it was considered a disease primarily of males. As a result, for many years,
      epidemiologic studies of the general population examining the prevalence of OSAS
      included only males and investigators examined almost exclusively males in their
      pathophysiologic studies. It has been widely recognized that OSAS in women is not
      as rare as it was originally believed. Whereas early studies of clinic
      populations suggested that females made up about 10% or less of OSAS cases, later
      studies of the general population suggest that about a third of all cases are
      females. This suggests that there may be clinical under-recognition of OSAS in
      females. We explore the reasons for the male predominance of OSAS, and the
      clinical under-recognition in females by examining differences in clinical
      presentation and polysomnography findings between male and female patients.

PMID- 12071543
TI  - Sleep behavior of South African adolescents.
AB  - STUDY OBJECTIVES: To survey a large group of South African adolescents about
      their sleep behavior, daytime behaviors, and morning alertness as compared to
      those of other teenagers worldwide. DESIGN: Subjects completed a questionnaire
      about their sleep habits and daytime behaviors on the previous day, and
      subjective morning alertness at the time of completing the questionnaire.
      SETTING: Four secondary schools in Johannesburg, South Africa on mid-week
      mornings. PARTICIPANTS: 825 secondary school students volunteered for this study.
      INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The students, (16+/-1 years), 61%
      female, reported significantly less time in bed (p<0.001) on a school night
      (453+/-70 minutes), compared to weekend nights (476+/-128 minutes). On the school
      night, they reported a mean sleep onset latency of 17 minutes, with 45% of the
      sample falling asleep in less than ten minutes. Short sleep onset latency and
      short in-bed wakefulness both were positively related to a high sleep efficiency
      and subjective sleep quality. On the previous day, 72% of the adolescents had
      consumed caffeinated beverages and 56% had exercised, but these behaviors did not
      significantly influence their nighttime sleep. The majority (77%) of students had
      napped the previous day and 8% had taken medication to fall asleep that night.
      40% of the students felt that they could fall asleep mid-morning, if given the
      chance, but their sleepiness was independent of their nighttime sleep quality or
      duration. CONCLUSIONS: Similarly to teenagers around the world, South African
      adolescents get insufficient sleep during the week, which they attempt to
      compensate for on the weekends. A large proportion of the students are also
      sleepy during the school day, which may influence their academic performance.

PMID- 12071544
TI  - Residential exposure to power frequency magnetic field and sleep disorders among
      women in an urban community of northern Taiwan.
AB  - STUDY OBJECTIVES: To investigate relationships between residential exposure to
      power frequency magnetic field and sleep initiation and maintenance disorders
      (SIAMD). DESIGN: A cross-sectional design conducted in an urban town of northern
      Taiwan in 1995-1996. SETTING/PATIENTS: A total of 5,078 married women aged 20-59.
      INTERVENTIONS: N/A. MEASUREMENTS: The residential magnetic field intensity was
      assessed using EMDEX II dosimeters. Trained interviewees collected self-reported
      information on SIAMD and other covariates. Three type-specific SIAMD were
      analyzed for associations with background, bedroom, and overall residential
      exposures. RESULTS: The prevalence rates of difficulty initiating sleep (DIS),
      difficulty maintaining sleep (DMS), and early morning awakening (EMA) were 29.5%,
      38.17%, and 26.02%, respectively. The DIS prevalence was significantly associated
      with bedroom magnetic field exposure of 2 miliGauss (mG) (odds ratio (OR)=1.20,
      95% confidence interval (CI)=1.02-1.40). The DMS prevalence was significantly
      higher for women with background exposure of 2 mG (OR=1.28, 95% CI=1.04-1.56). An
      elevated EMA prevalence was also significantly associated with all of the three
      exposure measures with excess risks ranging from 28% for overall exposure to 65%
      for background exposure. When magnetic field strength was analyzed as a
      continuous variable, background exposure, but not overall or bedroom exposure,
      showed a small but significant association with DMS and EMA (OR=1.05 per 1 mG
      increase, 95% CI=1.02-1.09). CONCLUSIONS: There is a modest association between
      residential exposures to elevated magnetic field intensity and insomnia
      complaints in women.

PMID- 12071545
TI  - Secondary narcolepsy in children with brain tumors.
AB  - We report two cases of children with disabling daytime sleepiness associated with
      suprasellar tumors and hypothalamic obesity. Multiple sleep latency testing
      demonstrated features consistent with severe narcolepsy, with sleep latencies of
      0.25 and 0.75 minutes, and REM latencies of 2.1 and 1.5 minutes, respectively. An
      additional patient with hypothalamic damage secondary to a brain tumor, who was
      thought to be in a vegetative state, had features of narcolepsy on
      polysomnography. All children responded well to treatment with stimulants. We
      speculate that secondary narcolepsy associated with hypothalamic tumors is due to
      damage or loss of hypothalamic hypocretin-containing neurons. In view of the good
      response to treatment, we recommend that all children with excessive daytime
      sleepiness and hypothalamic damage be evaluated for narcolepsy.

PMID- 12071546
TI  - HLA and hypocretin studies in Korean patients with narcolepsy.
AB  - STUDY OBJECTIVES: Very few studies have evaluated narcolepsy in Asian countries,
      outside of Japan. Our goal was to study narcolepsy at the genetic, clinical and
      pathophysiological level in Korea. DESIGN: Prospective study of consecutive
      patients and age matched controls. Clinical data ascertained from the Stanford
      Sleep Inventory, Polysomnography and MSLT data, as well as clinical notes. High
      resolution DRB1 and DQB1 typing in all subjects and studies of CSF hypocretin-1
      was also evaluated in a subset of patients. PARTICIPANTS AND SETTING: 20 patients
      diagnosed at St. Vincent and Korea University Hospitals (Seoul, Korea). 21 Korean
      control subjects. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: For narcoleptic
      subjects, mean age was 28.2 years old and 45% were female. Mean BMI was 23.9+/
      3.4 kg/m2, a significantly higher value than that expected in an age- and sex
      matched sample (p<0.01). All patients had sleepiness and cataplexy while the
      prevalence of other symptoms ranged from 60-75%. All but 2 subjects were HLA-DR15
      (DR2), DQB1*0602 positive (90%). This high DQB1*0602 percentage compared with 24%
      DQB1*0602 positivity in 21 control Koreans. Protective effects were observed for
      the DQB1*0601 and DRB1*0406 alleles, Hypocretin (orexin) CSF studies were also
      performed in 6 cataplectic subjects, all of which had undetectable CSF hypocretin
      levels. Two of these subjects had started narcolepsy less than 1 year before
      analysis yet had undetectable hypocretin levels. CONCLUSION: These results
      illustrate the similarity of narcolepsy-cataplexy in Korea in comparisons with
      other more studied populations. We also identified a new potential HLA protective
      subtype, HLA-DRB1*0406.

PMID- 12071547
TI  - A distinctive interaction between memory and chronic daytime somnolence in
      asymptomatic APOE e4 homozygotes.
AB  - STUDY OBJECTIVES: To correlate memory measures with a trait measure of chronic
      daytime somnolence in cognitively normal individuals with different gene doses of
      the apolipoprotein E (APOE) e4 allele, a common Alzheimer's disease
      susceptibility gene. DESIGN: Cross-sectional, exploratory study of cognitive
      abilities in APOE e4 homozygotes (HMZ) (n=42), heterozygotes (HTZ), (n=42) and
      noncarriers (NC) (n=42) who are matched for age, gender, educational level, and
      family history of dementia. SETTING: Tertiary care academic medical center.
      PARTICIPANTS: Cognitively normal residents of Maricopa County, Arizona who are 30
      70 years of age, genotyped for APOE, and have no history of a sleep disorder
      INTERVENTIONS: N/A. MEASUREMENTS: Epworth Sleepiness Scale (ESS) and a battery of
      neuropsychological tests RESULTS: Age, education, gender, and insomnia complaints
      did not significantly differ among groups. Despite normal baseline memory scores,
      memory declined with increasing ESS on all eight memory measures in the HMZ, two
      of eight in the HTZ, and one of eight in the NC. Differences between HMZ and NC
      on the slope of memory decline with increasing ESS reached statistical
      significance on two verbal memory measures, AVLT Long-Term Memory (p=0.048) and
      Percent Delayed Recall (p=0.035). CONCLUSIONS: Chronic daytime somnolence is
      associated with a distinctive decline in verbal memory in cognitively normal APOE
      e4 HMZ, a group at particularly high risk of Alzheimer's disease. Additional
      studies are needed to confirm these exploratory findings and to determine the
      effects of acute somnolence on cognition in these genetic subgroups.

PMID- 12071548
TI  - Cardiovascular and autonomic response to environmental noise during sleep in
      night shift workers.
AB  - Polysomnograph, beat-by-beat heart rate and blood pressure were monitored in
      night shift workers exposed to environmental and laboratory noise events during
      day sleep. The study was carried out in a sleep laboratory. Subjects were nine
      young, healthy female night shift workers. Recorded noises from trucks, civilian
      aircraft, low altitude military aircraft and tones were presented at 55, 65, and
      75 L(Amax). Sleep stage, heart rate, and systolic and diastolic blood pressures
      before and immediately after onset of noise events were compared. Spectral
      analyses of heart rate and blood pressure variabilities were used to compare
      sympathetic and parasympathetic nervous tone in 10-min. intervals containing
      noise and quiet. Heart rate was responsive to noise level but not noise type.
      Blood pressure increased primarily to sounds of sudden onset. Noise-induced
      awakening and alpha EEG responses were related to BP increase. Increase in HR was
      greatest when subjects were awakened by noise or already awake. Spectral analysis
      of BP variabilities indicated increased sympathetic vascular tone due to noise.
      Similar analyses of HR data indicated no noise effect. No habituation to noise
      was apparent over three consecutive sleep sessions. It was concluded that over
      the range of noise levels used, heart rate responds to noise level during sleep;
      blood pressure to sounds of sudden onset. Spectral analysis of blood pressure
      variabilities is a sensitive measure of autonomic nervous response to
      environmental noise and should also be studied in subjects sleeping at home.

PMID- 12071549
TI  - Rural aging: a global challenge. Keynote address, June 7, 2000.

PMID- 12071550
TI  - Preparing for the new world of longevity. Keynote address, June 8, 2000.

PMID- 12071551
TI  - Meeting the challenge of aging in the 21st century. Keynote address, June 9,
      2000.

PMID- 12071552
TI  - Rural aging: reduction of existing inequities. Keynote address, June 10, 2000.

PMID- 12071554
TI  - Demographic and health issues in rural aging: a global perspective.
AB  - The world is witnessing unprecedented changes in population structure, so that
      both the absolute number and proportion of older people are increasing worldwide.
      For many developing countries, rapid population aging and the phenomenon of a
      "double burden" of both infectious disease and emerging chronic diseases
      represent a major challenge. Many of those who will contribute to these
      extraordinary transitions will live in rural areas. Many countries, especially
      the poorest, still have a huge burden of infectious diseases, including
      increasing rates of HIV/AIDS along with a growing problem of chronic diseases. A
      number of critical policy considerations come to the fore in examining issues
      associated with rural aging, including: the need for rural development policies
      that take account of population aging and the needs of older people; improved
      coordination and integration of public health and care services in rural areas;
      support for nongovernmental organizations and community group efforts; and
      greater use of new technologies for communication. The year 1999 was pivotal for
      aging in terms of perceptions, attitudes, public action, better research and
      knowledge, and improved policy decisions that will benefit all of society into
      this new century. The Second United Nations World Assembly to be held in Madrid
      in April 2002 will provide further opportunity to build upon this progress and in
      the formulation of a new International Plan of Action on Aging to point the way
      for decisive action on positive policy and program initiatives for the future.

PMID- 12071553
TI  - Urban and rural dimensions of global population aging: an overview.
AB  - In keeping with the worldwide pattern of increased urbanization, the elderly
      population has become more concentrated in urban areas during the past 50 years.
      In developed countries as a whole, an estimated 73 percent of people aged 65 or
      over lived in urban areas in 1990, a figure that is projected to reach 80 percent
      by the year 2015. In developing nations, which are still predominantly rural,
      just over one-third of people aged 65 or over lived in urban areas in 1990,
      projected to exceed one-half by 2015. This article provides an overview of global
      data on urban elders, examines extant data on gender balances and migration
      patterns, and considers the importance of subnational urban/rural differences and
      whether rural elderly are disadvantaged relative to their urban counterparts.

PMID- 12071555
TI  - Health status of the rural elderly.
AB  - An enormous proportion of the worlds elderly live in rural areas and show wide
      variations in health status. Many, particularly those in the developing
      countries, are vulnerable to greater socioeconomic and health marginalization
      mainly due to inadequate provision of services and economic deprivation. As with
      the urban elderly, locomotor, visual and hearing disabilities, as well as life
      threatening conditions of coronary heart disease, diabetes and hypertension are
      common among rural elders also. Infections continue to take a heavy toll in many
      parts of the world. Higher prevalence of health and functioning impairments and
      of risk factors like sedentarism and current smoking have been reported for the
      rural elderly in developed countries like the United States, where less frequent
      use of certain preventive services also has been observed among the rural
      elderly. The positive association of well-being and health with variables such as
      living with family, having children, and community involvement, which has been
      reported from developing countries like Ghana and India, supports the usefulness
      of the time-honored value of joint family systems and lifelong social and
      physical activity--all known to foster healthy aging. Such traditional virtues
      therefore need to be preserved and strengthened. Effective geriatric health care
      services need to stress a community approach to primary health care, with
      provision of support and training for both family caregivers and professionals.
      In addition, emphasis on health promotion, cost-effective indigenous systems of
      medicine and gender-sensitive programs is needed.

PMID- 12071556
TI  - Rural bioethical issues of the elderly: how do they differ from urban ones?
AB  - Typical ethical issues in health care for the elderly include decision making for
      elderly patients with and without capacity, advance directives, the use of life
      sustaining technologies, and questions of access to services and justice.
      Obviously the same issues are relevant for elderly patients in rural settings.
      But the unique features of rural living add another dimension to ethical
      discourse and the care of patients, namely the primary importance of
      relationships. Rural bioethics is based on an ethic of familiarity, which alters
      our attention to such issues as confidentiality, multiple relationships, scope of
      practice, and access issues. The following article briefly outlines the unique
      features of rural bioethics and provides a case analysis.

PMID- 12071557
TI  - Training to provide for healthy rural aging.
AB  - More than 60 percent of the worlds aged population is in developing countries,
      the majority living in rural and remote areas. Resources in these areas are
      scarce and there is a lack of services and programs, especially in the areas of
      health, housing and social welfare. The most serious deficiency faced by many
      countries in meeting the challenges of population aging is the pronounced
      scarcity of trained caregivers. Little attention has been given to developing
      effective training policies and programs. Most of the people providing a service
      to older people lack basic training and this is more so in rural and remote
      areas. The processes for extending healthy aging and postponing the onset of
      chronic diseases and disabling conditions exist already. Unfortunately, these
      processes are not disseminated in appropriate ways. It is therefore imperative to
      disseminate this information by training people at the grass roots level to reach
      the most vulnerable and isolated older people. Primary care workers should have
      the necessary skills, knowledge and techniques to facilitate good care of older
      people in their environment. This article reviews and analyzes attempts being
      made by a number of countries to meet this need. Though the basic issues dealt
      with are often the same, the approach used differs.

PMID- 12071558
TI  - Community-based rehabilitation: better quality of life for older rural people
      with disabilities.
AB  - This article describes various categories of disability occurring in old age and
      goals that rehabilitation aims to achieve. It suggests that in rural areas these
      goals could be attained through application of rehabilitation care on a community
      level, provision of appropriate assistive technology and adaptation of the
      immediate environment.

PMID- 12071559
TI  - Long-term care in rural West Virginia: managed care and future roles for the
      aging network.
AB  - The managed care movement emphasizes the rationalization of health care delivery
      through fixed price or capitation of service and the utilization of a preferred
      physician or health gatekeeper. These features are advanced as measures of cost
      control in health care delivery. This approach presents the aging network,
      established under the Older Americans Act, with a number of daunting challenges
      which are particularly acute to service providers in rural areas. How this
      network responds will determine its future efficacy in the delivery of health and
      long-term care services. This article examines these concerns among eight rurally
      based senior centers and two Area Agencies on Aging in Southern West Virginia.
      Issues of management capacity, present and future positioning, and receptivity to
      managed care are emphasized. These providers stand on the strengths of a long
      tradition of serving clients, knowledge of their needs and face-to-face
      interactions with them--capabilities managed care organizations do not have.
      However, little outreach to managed care in these areas has occurred.

PMID- 12071560
TI  - Finding and using rural aging data: an international perspective.
AB  - This article reports on a workshop in which participants identified sources of
      data on rural aging. Such sources are typically part of larger data collection
      efforts or special aging studies with large rural components. Finding and using
      data on rural aging are not only two different processes but they also face
      somewhat different obstacles and the solutions are likewise different. The
      workshop addressed both of these issues. Participants shared many innovative and
      creative means for collecting, finding and adapting more general data sources,
      and analyzing and using these data, to further our understanding of rural aging
      phenomena.

PMID- 12071561
TI  - Access and issues of equity in remote/rural areas.
AB  - This article reports on a workshop in which the major focus was a review of the
      barriers that prevent access to the array of community-based services available
      to the rural elderly. The demographics of the elderly were outlined and key
      components of the service system described. Attention was given to access
      hospital-based care, the closing of hospitals and the reasons for bypassing rural
      hospitals for those in large towns or cities. Special emphasis also was given to
      mental health services and their uneven accessibility. A review of the policy
      implications closed the workshop.

PMID- 12071562
TI  - Vision, visual needs, and quality of life of older people in rural environments:
      a report and synthesis of a meeting.
AB  - Vision as an aspect of rural aging was a major portion of the First International
      Conference on Rural Aging. Various perspectives on the relationship of vision to
      rural aging were presented in two symposia, two paper sessions, one workshop and
      the poster session (a total of 28 presentations). In summarizing this rich and
      varied material, the author emphasizes that: (a) vision is important to
      maintaining a healthy, active life as one ages; (b) impaired vision is generally
      preventable or treatable; (c) well-designed community programs can assist in
      prevention and treatment; and (d) assessing the effects of these programs
      requires evaluation of patients' quality of life. More research is needed to
      refine strategies for creating, maintaining and evaluating community-based eye
      care programs and integrating them with existing public health or other community
      programs.

PMID- 12071564
TI  - Telepsychiatry: challenges in rural aging.
AB  - A significant health care dilemma for older individuals living in rural areas is
      that at a time in life when there is, predictably, a greater need for medical
      services, the ability to access those limited services is markedly reduced.
      Telepsychiatry presents an innovative and cost-effective strategy for the
      provision of improved local access to quality mental health services for the
      underserved rural elderly. Telepsychiatry has demonstrated the potential to
      improve access to mental health services, provide those services in an affordable
      and cost-effective manner and deliver those services at a quality nearly equal to
      traditional face-to-face services. Advances in telepsychiatry technology allow a
      core group of skilled mental health providers in a central location to provide
      timely local access to quality services for the rural elderly over a broad
      geographic area.

PMID- 12071563
TI  - The public health perspective in health promotion and disability prevention for
      older adults: the role of the Centers for Disease Control and Prevention.
AB  - As the United States federal public health agency, the role of the Centers for
      Disease Control and Prevention (CDC) in health promotion and disability
      prevention with older adults encompasses research, surveillance and program
      activities in aging. This article characterizes the objectives and context of
      prevention in later life and summarizes CDCs functions, collaborative
      partnerships with public health agencies and other organizations, and range of
      activities in older adult health. As a major focus of these efforts, chronic
      disease risk reduction is examined through CDC's efforts in the area of physical
      activity; a longitudinal investigation of osteoarthritis in an older biracial
      rural population; and chronic illness self-management programs as a prototype for
      secondary prevention. Other CDC activities highlighted include addressing the
      burden of vaccine-preventable diseases through CDC-funded programs to improve
      immunization coverage in older adults, and falls prevention interventions and
      resources. Future directions in aging at CDC are also outlined.

PMID- 12071565
TI  - Social services for the elderly based on the new rurality: the Japanese
      experience.
AB  - Since the 1920s, Japan has changed from being a relatively youthful society, with
      an average age of about 26, to an elderly society with an average age of over 40
      (Fordyce, 1999). The number of elderly is rising and the number of births is
      falling. Concurrently, the health and infrastructure needs of many of the retired
      elderly are increasing while, for the same retirees, their contribution to
      productivity and revenue is diminishing (Fordyce, 1999). As the population ages,
      inevitably the burdens of taxes, pensions, public medical insurance and social
      services have been rapidly increasing. To meet the challenges of these changes in
      population structure, Japan has established policies such as the Gold Plan and
      the Public Long-term Care Insurance Program and it has expanded social services
      into rural agricultural areas. This article examines those policies and the care
      services and productive aging programs that have developed due to population
      aging and new rural patterns in Japan.

PMID- 12071566
TI  - Conclusions and recommendations for policies on rural aging in the first decades
      of the 21st century.
AB  - The 2000 Forum on Rural Aging: Policy Debates was one of the main tracks of the
      first International Conference on Rural Aging held in Charleston, WVa., in June
      2000. The 2000 Forum was a follow-up to the Expert Group Meeting on Rural Aging,
      which met at Shepherdstown, WVa., in May 1999. That group considered policy
      implications of the 1999 International Year of Older Persons for rural aging in
      four key areas: the situation of older people, multigenerational relationships,
      lifelong development, and the development and aging of rural populations. As a
      direct follow-up of the Shepherdstown Expert Group Meeting, the 2000 Forum on
      Rural Aging formulated the Conclusions and Recommendations for Policies on Rural
      Aging through a series of working groups. The Conclusions and Recommendations
      were endorsed by the Conference Plenary Session on June 11, 2000. The Draft
      Recommendations for Policies on Rural Aging were availablefor comments on the
      Internet in the remaining part of the year 2000. Many comments were received.
      Hana Hermanova and Sally Richardson incorporated the comments into the finalized
      version.

PMID- 12071567
TI  - Public awareness of stuttering in Shanghai, China.
AB  - This study reports the results of an investigation of knowledge and public
      awareness of stuttering among laypersons in Shanghai, China. A total number of
      1968 respondents answered a questionnaire including questions about prevalence,
      onset, gender distribution and occurrence in different cultures, cause,
      treatment, intelligence and heredity of stuttering. Stuttering appears to be a
      disorder that most people in the Shanghai area are familiar with, and for several
      aspects a considerable number of respondents held views that are in line with
      current knowledge about stuttering. For some aspects though knowledge is limited,
      indicating a need for disseminating scientific information on stuttering. The
      results of the present study are compared with a similar Belgium study.

PMID- 12071568
TI  - Prosodic variation across sampling tasks in normal and dysarthric speakers.
AB  - Speech assessments are commonly based on structured elicitation tasks. Despite
      the value of these tasks, the extent to which their results are a valid
      reflection of natural speech performance is being increasingly questioned. This
      is particularly warranted in the light of research findings indicating
      significant differences in normal speech behaviour across sampling tasks. There
      is, however, a paucity of research into how disordered speakers' performance
      varies across elicitation tasks. This study investigated ten prosodic parameters
      in structured and unstructured speech tasks (reading and conversation) in 12
      dysarthric and 12 control subjects. The results suggest that the nature of
      sampling task affected dysarthric speakers differently to the control group. The
      implications of these findings for the assessment of disordered speakers are
      addressed.

PMID- 12071569
TI  - Tongue-to-palate contact patterns and variability of four English consonants in
      an /i/ vowel environment.
AB  - Minimal data exist describing tongue-to-palate contact patterns and their
      variability in normal speakers of English. Consequently, the aims of the present
      study were to examine, using a comprehensive profile of data analysis, tongue-to
      palate contact patterns and their variability in a group of ten normal speakers
      of English using the Reading Electropalatography3 (EPG3) system. Each speaker
      produced ten repetitions of the target words tea, leap, sea, and key following
      the carrier phrase 'I saw a ...'. Results revealed that the contact patterns
      produced exhibited similar characteristics to those described in earlier
      research. Additionally, the lateral approximant /i/ exhibited the highest degree
      of intra-subject variability with the alveolar fricative /s/ exhibiting the
      least. The results of this study are discussed in relation to existing normative
      data.

PMID- 12071570
TI  - A simple subspace approach for speech denoising.
AB  - For pathological voices, hoarseness is mainly due to airflow turbulence in the
      vocal tract and is often referred to as noise. This paper focuses on the
      enhancement of speech signals that are supposedly degraded by additive white
      noise. Speech enhancement is performed in the time-domain, by means of a fast and
      reliable subspace approach. A low-order singular value decomposition (SVD) allows
      separating the signal and the noise contribution in subsequent data frames of the
      analysed speech signal. The noise component is thus removed from the signal and
      the filtered signal is reconstructed along the directions spanned by the
      eigenvectors associated with the signal subspace eigenvalues only, thus giving
      enhanced voice quality. This approach was tested on synthetic data, showing
      higher performance in terms of increased SNR when compared with linear prediction
      (LP) filtering. It was also successfully applied to real data, from hoarse voices
      of patients that had undergone partial cordectomisation. The simple structure of
      the proposed technique allows a real-time implementation, suitable for portable
      device realisation, as an aid to dysphonic speakers. It could be useful for
      reducing the effort in speaking, which is closely related to social problems due
      to awkwardness of voice.

PMID- 12071571
TI  - Critical issues in benchmark calculations from continuous data.
AB  - The benchmark dose (BMD) is a dose that causes a specified low level of
      additional risk and is estimated using a statistical dose-response analysis.
      Regulatory agencies are using a statistical lower bound on the BMD in the place
      of the NOAEL for establishing exposure limits. However, there are still several
      issues regarding the BMD for which no clear consensus has emerged, particularly
      with respect to calculation of BMD from continuous response data. These include:
      (1) how to define the BMD from continuous data so that they are comparable to BMD
      derived from binary data, (2) what dose-response models and levels of additional
      risk should be used to calculate the BMD. The "hybrid" approach (Gaylor and
      Slikker, 1990; Crump, 1995) expresses the BMD from continuous data in terms that
      are directly comparable to those obtained using binary data. Several features of
      the hybrid approach are examined, with the emphasis on application to
      epidemiological data. The effect on the BMD of converting continuous data to
      binary form is quantified. Model uncertainty is explored, and the need for
      controlling this uncertainty by restricting the class of allowable models is
      demonstrated. Control data, which are often not available in epidemiological
      studies, are shown to have a limited effect upon the BMD so long as the model for
      the mean response is linear or convex. Such models are also biologically
      plausible, at least at low doses. Based on these and other considerations,
      suggestions are made for selecting a model for applying the hybrid approach and
      for selecting the level of additional risk on which to base the BMD.

PMID- 12071572
TI  - Benzene and leukemia.

PMID- 12071573
TI  - The retinoid signaling system--a target in dioxin toxicity.
AB  - This review summarizes the available data on the effects of dioxins on retinoid
      levels, retinoid-related enzyme activities, and toxicological endpoints that have
      been correlated to retinoid effects. Similarities between dioxin toxicity and
      retinoid deficiency as well as retinoid excess are pointed out. Several possible
      levels of interaction between the dioxin and the retinoid signaling pathways are
      discussed, including the involvement of the Ah receptor, altered retinoic acid
      homeostasis, and an altered set point for retinoid storage. A hypothesis for the
      effect of dioxins on retinoids is suggested. In this hypothesis, comprising two
      cascades of effects on the molecular level, the effect of dioxins on retinoic
      acid levels is central.

PMID- 12071574
TI  - IgA-antitissue transglutaminase: validation of a commercial assay for diagnosing
      coeliac disease.
AB  - We have evaluated a commercial assay for serum IgA class antibodies to tissue
      transglutaminase, the enzyme identified as the major endomysial autoantigen in
      coeliac disease (CD). Sera were available from 130 adults diagnosed with CD in
      Southern Derbyshire between 01 01 97 and 31 12 99. Sera from 100 patients without
      villous atrophy on small intestinal biopsy were controls. The ability of the
      assay to detect abnormally low total IgA levels was assessed using sera from 18
      subjects with IgA deficiency. Sensitivity and specificity of this IgA-anti tissue
      transglutaminase (tTGA) assay (86.2%, 91.0%) were inferior to endomysial antibody
      (EMA; 93.8%, 100%). tTGA has significantly higher sensitivity than IgA
      antigliadin (76.2%). tTGA was appropriately undetectable (<0.03 U/mL) in 17 of 18
      subjects with selective IgA deficiency. The high likelihood ratio (35) for tTGA
      at levels >9.0 U/mL and methodological advantages over EMA suggest that tTGA
      could be used as a first line diagnostic test for CD. At tTGA levels of 4-9 U/mL,
      use of EMA as a second line test would improve specificity.

PMID- 12071575
TI  - Platelet membrane glycoproteins in haemostasis.
AB  - Platelets play a critical role in both primary and secondary haemostasis. In
      primary haemostasis, specialised glycoprotein receptors enable platelets to
      adhere to proteins that are exposed in areas of vascular damage. The process of
      adhesion, and/or the interaction of soluble agonists with receptors on the
      platelet, activates the platelets, which are then able to aggregate together.
      This aggregation creates a platelet plug that seals the breach in the vessel wall
      and prevents excess blood loss. Activated platelets then facilitate secondary
      haemostasis, the formation of a fibrin clot, by carrying coagulation factors and
      providing a catalytic surface for the major interactions of the coagulation
      cascade. This review briefly describes the adhesion, activation and aggregation
      of platelets; their role in blood coagulation and clot retraction; and how they
      may be inhibited in order to prevent thrombosis in at-risk patients.

PMID- 12071576
TI  - Detection of procalcitonin (PCT) in healthy controls and patients with local
      infection by a sensitive ILMA.
AB  - BACKGROUND: Procalcitonin (PCT) is an established marker for severe systemic
      bacterial infection and sepsis. So far the relevance of PCT in healthy
      individuals or patients with local infections is unclear due to the lack of
      highly sensitive assays. The aim of our study was the characterization of a new
      sensitive PCT assay, the establishment of reference values and the assessment of
      diagnostic accuracy. METHODS: We assessed PCT values in 522 patients with
      different infectious and non infectious conditions and 410 healthy controls by a
      new coated tube sandwich chemiluminescence assay B.R.A.H.M.S ProCa-S (2 step
      assay, time to result 2.5 hours). RESULTS: The lower detection limit was 6.0
      ng/L, with a functional assay sensitivity below 7 ng/L. Samples above 250 ng/L
      gave excellent correlation to the LUMItest PCT (r = 0.98, p < 0.0001). There was
      no high dose hook effect up to a concentration of 21,300 ng/L. The 410 healthy
      controls had a median concentration of 12.7 ng/L (95% CI: 12.6-14.7 ng/L). 65
      controls had non-detectable PCT values (defined as 5 ng/L). The 2.5th percentile
      of the normal population was 5 ng/L and the 97.5th percentile was 46.7 ng/L. ROC
      plot analysis resulted in an area under the curve (AUC) of 0.90. The optimal
      decision threshold was at 50 ng/L, with a sensitivity for infection of 77.8% and
      a specificity of 98.5% (positive predictive value 97.7%, negative predictive
      value 84.9%). There was a highly significant (p < 0.0001) difference in the PCT
      median between healthy individuals and patients with infections (e.g. pneumonia,
      peritonitis) but not non-infectious controls (e.g. pregnancy, autoimmune
      disease). CONCLUSIONS: The new PCT assay is 30 times more sensitive than the
      established routine assay LUMItest PCT, thus allowing for the first time PCT
      detection in healthy individuals. First results indicate that the assay is
      suitable to differentiate local bacterial infections from other non-infectious
      diseases.

PMID- 12071577
TI  - Clinical aspects of Rh genotyping.
AB  - The Rh antigens are encoded by the RHD and RHCE genes. In RhD negative
      individuals the RHD gene is absent or grossly deleted. Routinely, Rh typing is
      performed by haemagglutination. However, there are some clinical situations in
      which serological techniques are not suitable for determining the red blood cell
      phenotype accurately. Most anti-D sera may not agglutinate erythrocytes
      possessing a reduced expression of the D antigen. In these cases, DNA-based
      analyses may be better than serological typing to infer the appropriate
      phenotype. Agglutination methods are also of limited use for determining the red
      blood cell phenotype of a foetus at risk of haemolytic disease of the newborn.
      Molecular RHD typing using amniocytes or DNA obtained from maternal plasma may
      obviate the need of amniocenteses during pregnancy when the foetus is RhD
      negative, thus providing an important tool in managing possible sensitization by
      foetal erythrocytes. Classical haemagglutination has limitation in patients with
      autoimmune haemolytic anaemia. Erythrocytes coated with IgG cannot be accurately
      typed for red blood cell antigens, particularly when directly agglutinating
      antibodies are not available or IgG removal by chemical treatment is
      insufficient. Molecular genotyping is very important for determination of the
      true blood group antigens of these patients. RHD genotyping with a specificity
      and sensitivity comparable to serologic methods is of practical importance to
      overcome the limitations of serology and, in addition, to improve the currently
      possible resolution.

PMID- 12071578
TI  - Residual risk of HIV-1 transmission: the case of a seroconverter.
AB  - In the present report we describe the case of a repeat blood donor infected with
      HIV-1. In January 2000 the donor was found to be repeatedly reactive to HIV1/2
      antibodies and HIV-1 RNA screening tests. The donation was confirmed to be HIV-1
      positive by Western blot. During the post-test counselling session, the donor
      reported a risk sexual behaviour denied during the pre-donation interview, and he
      recalled that in May 1998 he had undergone a check-up including the test for the
      detection of HIV1/2 antibodies, which was negative. This check-up was dated four
      months the next to the donor's previous donation in January 1998, which had been
      found HIV1/2 antibody negative, too. Serum and plasma specimens, properly stored
      at -80 degrees C, were available at the hospital where the donor had undergone
      the HIV antibody test in May 1998. Thus, the specimens dated May 1998 and the
      specimen of the last donation in January 2000 were investigated again by using
      the most sensitive tests currently available in the setting of donation
      screening. On the whole, the results suggest that in May 1998 the donor was in
      the pre-seroconversion period for HIV-1 infection. The case reported here
      stresses that a residual risk for HIV transmission through blood products still
      relies on the possibility that an individual may be accepted as blood donor
      during the asymptomatic pre-seroconversion window period of HIV-1 infection.
      Actually, this phase of the infection cannot be detected by the routine
      antibody/antigen-based HIV1/2 screening tests but only by using more sensitive
      techniques such as genomic screening.

PMID- 12071579
TI  - Anti-inflammatory and antithrombotic effects of statins in the management of
      coronary artery disease.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), a potent
      class of cholesterol-lowering drugs, exert a number of pleiotropic effects,
      including anti-inflammatory and antithrombotic properties. Evidence is now
      accumulating that these effects are not related to the reduction in lipid levels.
      In vitro studies, supported recently by in vivo data, indicate that treatment
      with statins results in a significant decrease in the levels of inflammation
      markers, such as C-reactive protein, interleukin 6, and tumor necrosis factor
      alpha, which appear to be predictors of acute coronary events and help stratify
      cardiovascular risk. Up to now, only high-sensitive C-reactive protein testing
      has the potential to become an adjunctive method to assess the risk of coronary
      events in low- and high-risk individuals. Statins can also inhibit tissue factor
      expression, leading to impaired activation of the blood coagulation cascade, as
      evidenced by a decrease in thrombin generation in vivo. Interrelated inhibition
      of inflammation and thrombosis induced by statins is believed to largely
      contribute to clinical benefits from statin therapy, regardless of cholesterol
      levels. Further studies will answer the question whether markers of inflammation,
      other than C-reactive protein and possibly indices of thrombin formation, might
      improve cardiovascular risk stratification.

PMID- 12071580
TI  - Human cytomegalovirus salivary antibodies as related to stress.
AB  - Human cytomegalovirus (HCMV) is prevalent in 50-80% of the population worldwide.
      After primary infection it remains in a latent state until reactivation.
      Stressful events induce the release of corticosteroids which activate HCMV. The
      effect of examination stress on HCMV reactivation among first year female
      students was studied by detecting the values of HCMV specific salivary IgG and
      IgA antibodies before, during and after two important examinations. Hepatitis A
      virus (HAV) salivary antibodies served as a non-latent virus control. A
      statistically significant increase in the level of HCMV specific IgG and IgA
      antibodies was detected in saliva samples collected during the two examinations,
      as compared with the samples collected one month before them and two weeks after
      the grades were posted (p<0.05), whereas HAV antibody levels did not change
      significantly.

PMID- 12071581
TI  - Influence of endurance exercise (triathlon) on circulating transferrin receptors
      and other indicators of iron status in female athletes.
AB  - Numerous reports have described a poor iron status in female endurance athletes.
      However, the traditionally applied indicators of iron status (hemoglobin,
      ferritin, transferrin) may not truly reflect the iron status. Therefore we
      studied the newly developed soluble transferrin receptor and other indicators of
      iron status in twelve female endurance athletes before and after a triathlon
      race. Resting values showed a poor iron status in the participants of the race.
      Serum TfR concentration increased slightly after the race. However, if the values
      are corrected for hemoconcentration no change could be found. Hemoglobin, serum
      ferritin and transferrin values were increased after the race.

PMID- 12071582
TI  - Evaluation of an improved immunoturbidimetic assay for serum C-reactive protein
      on a COBAS INTEGRA 400 Analyzer.
AB  - Recent studies have shown that C-reactive protein (CRP) can be used as a
      prognostic risk marker of cardiovascular disease. This new clinical indication
      requires accurate and precise measurement of CRP at low concentrations (<5 mg/L).
      We evaluated the analytical performance of an improved CRP immunoturbidimetric
      method (CRPLX from Roche Diagnostics) on a COBAS INTEGRA 400 analyzer. The assay
      is simple and rapid to perform with low sample volume (2.5 microl). The limit of
      detection is 0.26 mg/L, with a working range extending to 194 mg/l. The method
      shows low imprecision in the whole dynamic range, with a day-to-day coefficient
      of variation of 10% at a CRP concentration of 0.66 mg/L. There is no interference
      by bilirubin, hemoglobin, triglycerides and rheumatoid factor up to high
      concentrations. It compares well with a high sensitivity nephelometric assay,
      widely used as reference method, and with a classical turbidimetric assay. We
      conclude that this CRP assay offers to the clinical laboratory an efficient and
      reliable alternative tohigh sensitivity immunoassays in the new CRP applications.

PMID- 12071583
TI  - Use of the anti-endomysial antibody test to diagnose coeliac disease in clinical
      practice.
AB  - BACKGROUND: Guidelines suggest that duodenal biopsies should be taken in patients
      with iron deficiency anaemia. OBJECTIVE: To examine anti-endomysial antibody
      (anti-EMA) and duodenal biopsy testing in Portsmouth, UK. To evaluate if the
      current pathology workload can be reduced by anti-EMA replacing some duodenal
      biopsies. To determine to what extent doctors in Portsmouth are confirming a
      positive anti-EMA test by small bowel biopsy. DESIGN: Patients' records were
      examined firstly from whom duodenal biopsies were taken between April 1999 and
      September 2000, and secondly who had anti-EMA tested between December 1999 and
      September 2000. SETTING: Queen Alexandra Hospital, UK. District General Hospital.
      Medical Outpatients Department. RESULTS: In the first group, of 354 patients
      undergoing duodenal biopsy, 108 patients had anti-EMA tested. Of these 108
      patients, 25 had positive IgA anti-EMA and 83 had negative IgA anti-EMA. Of these
      83 patients who had negative IgA EMA, 8 patients had a duodenal biopsy suggestive
      of Coeliac Disease. 4 of these 8 patients were on gluten free diets at the time
      of anti-EMA testing so were excluded. 1 of the 4 patients who had a duodenal
      biopsy indicative of Coeliac Disease had a positive IgG anti-EMA despite negative
      IgA anti-EMA. Therefore 3 false negative IgG anti-EMA were ultimately identified
      giving a sensitivity of 89% and a specificity of 100%. On follow up one has
      subsequently been found to have T-cell lymphoma; if this patient is taken into
      account the sensitivity of anti-EMA increases to 93%. In the second group; 1450
      patients had anti-EMA tested. Of the 67 positive anti-EMA tests in this group
      only 12 had a duodenal biopsy. CONCLUSIONS: Many patients who have been tested
      for anti-EMA are not offered duodenal biopsy in Portsmouth despite current
      British Society of Gastroenterology (BSG) guidelines, although it should be noted
      that the BSG guidelines on iron-deficiency anaemia recommend using anti-EMA
      without histology to exclude Coeliac Disease in menstruating women (biopsy would
      still be recommended if anti-EMA were positive). Our study has found a high
      sensitivity and specificity of anti-EMA; there may therefore be some
      circumstances where duodenal biopsy is unnecessary in the investigation of
      Coeliac Disease. Patients with suspected Coeliac Disease and negative anti-EMA
      should be evaluated for other causes of villous atrophy.

PMID- 12071584
TI  - Impact of laboratory testing on DRG coding and reimbursement--results of a data
      base research.
AB  - We filed an Australian data base with about 7 million well-documented clinical
      cases for comorbidities, which can be proven, supported or excluded by laboratory
      testing and which have an impact on DRG reimbursement. The result was a list of
      123 DRGs being shifted to a higher severity level by documenting one out of 157
      complications. For better visualization of the more than 4,000 combinations, we
      developed a computer program, which allows the laboratory to develop its own
      diagnostic pathways for these complications in a simple Excel format.

PMID- 12071585
TI  - Pharmacogenetics and the future of medical practice.
AB  - Pharmacogenetics, in the different scenarios included in this term, will
      represent an important new avenue towards understanding disease pathology and
      drug action, and will offer new opportunities of stratifying patients to achieve
      optimal treatment success. As such, it represents a logical, consequent step in
      the history of medicine--evolution, rather than revolution. Its implementation
      will take time, and will not apply to all diseases and all treatments equally. If
      society finds ways to sanction the proper use of this information, thus allowing
      and protecting its unencumbered use for the patient's benefit, important progress
      in health care will be made.

PMID- 12071586
TI  - Rat renal function four days after bile-duct ligation: effects of indomethacin
      and vasoactive agents.
AB  - The purpose of this study was to assess the effects of the cyclooxygenase
      inhibitor, indomethacin, and some vasoactive agents on the renal functional
      parameters during the early liver injury induced by four days bile duct ligation
      (BDL). Wistar rats with four days-BDL and control-sham operated were used. Renal
      function was measured in anesthetized rat treated with a single dose of
      indomethacin (control, 0.3, 1.0, 3.0 mg/kg b.w.; i.v.) one hour before clearance
      studies. Sulindac effects were also evaluated (5 mg/kg b.w., i.p). Isolated rat
      kidney preparations from control and BDL donor rats were used to study renal
      vascular response to noradrenaline, carbachol or sodium nitroprusside. The bile
      duct ligation promoted a diminished renal cortical plasma flow (RCPF) on the
      fourth day post surgery accompanied with a diminution in the glomerular
      filtration rate (GFR), increased filtration fraction and increased fractional
      excretion of water and sodium. Indomethacin 0.3 mg/kg induced an increase in GFR
      and RCPF, maintaining the high filtration fraction in BDL rats. The other doses
      did not alter these parameters as compared with bile duct ligated rats without
      treatment, but indomethacin 3 mg/kg caused a significant increase in filtration
      fraction. Indomethacin induced dose-dependent diminution in natriuresis in sham
      and BDL groups. Sulindac did not modify hemodynamic parameters, but induced
      antinatriuresis and antidiuresis in both experimental groups. Maximal vascular
      responses to noradrenaline measured in isolated rat kidneys were statistically
      diminished in BDL-rats as compared with controls (C, n=7; 35.0+/-2.3 mmHg ml(-1)
      min; BDL-rats, n=5; 23.8+/-0.7 mmHg ml(-1) min; p<0.02), without changes in EC15.
      Maximal relaxation induced by sodium nitroprusside in the phenylephrine (PHE)-pre
      constricted renal vasculature in control preparations did not differ from that
      observed in BDL group (C: n=6; 49.5+/-2.3%). Values of EC50 were 1.26+/-0.07
      microM (n=6) in control preparations and 0.34+/-0.03 microM (n=4) in kidneys from
      BDL-rats (p<0.001). Carbachol induced a biphasic relaxation of PHE-pre
      constricted renal vasculature. No differences in maximal responses were found.
      EC50 value of the second phase in BDL group was significantly decreased compared
      to control preparations (C: n=6, 0.47+/-0.05 microM; BDL: n=6, 0.22+/-0.03 microM
      p<0.001). The present results show that the altered renal function after a short
      time post bile duct ligation is determined, at least in part, by increased
      release of arachidonic derivatives in vascular bed and tubular cells. At this
      stage of liver injury, the alteration in the renal vascular response to different
      vasoactive agents is remarkable.

PMID- 12071587
TI  - Acute uremia in rats: feeding sucrose overnight is preferable to starvation.
AB  - Some experiments on uremia in rats may require an overnight fast in order to
      empty the gastrointestinal tract, or for other reasons. Previous investigation of
      normal rats showed that an overnight fast is not completely innocuous and that
      feeding pure sucrose is a valuable alternative. In the present study, anephric
      uremic rats were fasted or fed sucrose for 20 h. Sucrose feeding resulted in
      lower serum urea values and less loss of liver weight. Therefore, feeding sucrose
      overnight is preferable to starvation in uremic rats, as in normal rats.

PMID- 12071588
TI  - Inhibitory effect of murine kidney extracts on mast cells derived from human
      umbilical cord blood.
AB  - We examined the effect of aqueous murine kidney extract (MKE) on the growth of
      mast cells prepared from the liquid culture of human umbilical cord blood CD34+
      cells in the presence of a combination of recombinant human stem cell factor
      (SCF) and interleukin-6 (IL-6). Cultured cells were mature mast cells that
      expressed CD117 antigen on their surface, a specific marker for human mast cell,
      and they contained 6.53 pg histamine per cell. Adding MKE resulted in a 53%
      inhibition of mast cell growth and a 40% decrease in histamine content in mast
      cells in a serum-free liquid culture stimulated by SCF and IL-6. The inhibitory
      molecule for the growth of human mature mast cells was estimated at about 30 kDa
      of protein from gel-filtration HPLC. This fraction also inhibited the growth of
      murine peritoneal cells-derived mast cells. These results suggest that MKE
      contains regulator(s) that suppress the growth of mast cells and histamine
      synthesis. and that act beyond species specificity.

PMID- 12071589
TI  - Different patterns of renal cell killing after warm and cold ischemia.
AB  - Kidneys preserved for transplantation surgery sustain injuries caused by cold
      ischemia during storage. Additionally, kidneys harvested from non-heart-beating
      donors encounter the stress of warm ischemia. The aim of this study was to
      determine the specific cell types losing viability after warm and cold ischemia.
      In warm ischemia studies, the pedicles of left kidneys of Lewis rats were cross
      clamped for up to 90 min. In cold ischemia studies, kidneys were flushed with
      cold University of Wisconsin solution and stored up to 48h at 0-1 degrees C.
      After warm or cold ischemia, kidneys were perfused via the renal arteries with
      Krebs-Henseleit bicarbonate (KHB) buffer at 37 degrees C, followed by trypan blue
      to label the nuclei of nonviable cells. Warm ischemia for 90 min caused renal
      failure and led to injury of proximal tubular cells, e.g., loss of brush borders,
      cast formation and trypan blue labeling. Cold ischemia for 48 h also caused renal
      failure but, unlike warm ischemia, caused trypan blue labeling of glomerular
      podocytes and peritubular endothelial cells. In warm ischemia-induced injury,
      electron microscopy showed shedding of microvilli and marked swelling of proximal
      tubular cells, microvilli and mitochondria. In cold ischemia-induced injury,
      podocytes were blebbed and swollen, and their pedicels were detached from the
      basement membrane, but disruption in proximal tubules was milder. In conclusion,
      warm ischemia triggers injury primarily to proximal tubular cells, whereas cold
      ischemia damages glomerular podocytes and peritubular endothelial cells in
      addition to proximal tubules.

PMID- 12071590
TI  - Long-term intravenous calcitriol in secondary hyperparathyroidism: the role of
      technetium-99m-MIBI scintigraphy in predicting the response to treatment.
AB  - BACKGROUND: Despite the effectiveness of intravenous calcitriol in suppressing
      parathyroid hormone secretion in patients with uremic hyperparathyroidism, 50% of
      the patients remain refractory to this treatment. There are conflicting reports
      regarding the factors that can predict the response to treatment. Technetium-99m
      MIBI scintigraphy was found to be correlated with functional activity of the
      parathyroid gland. METHODS: We, retrospectively, evaluated 16 chronic
      hemodialysis patients, who were maintained on i.v. calcitriol for 36 months or
      longer, and who had MIBI scan either at the start of, or within the first 6
      months of starting calcitriol. Nine patients had a positive uptake (+ve group),
      and 7 patients had a negative uptake (-ve group). All patients had an elevated
      iPTH (iPTH > 300 pg/ml) at the start of treatment. RESULTS: The percentage
      reduction of iPTH in the (-ve) and the (+ve) groups was 65% versus 45% at 12
      months, and 65% versus 10% at 36 months respectively. In long-term follow-up of
      36 months, all the patients in the (-ve) group responded to calcitriol; while 8
      of the 9 patients (89%) in the (+ve) group didn't respond. The difference in
      response between the 2 groups was statistically significant (p<0.001).
      CONCLUSION: We conclude that MIBI scan is a reliable technique in predicting the
      response to treatment with i.v. calcitriol in patients with secondary
      hyperparathyroidism.

PMID- 12071591
TI  - Left ventricular hypertrophy is a risk factor independent of hypertension in
      survival of hemodialyzed patients.
AB  - Hemodialysis patients have low 5-year survival rates of approximately 60%, and
      the most common cause of death is cardiovascular diseases. Their population may
      be considered, therefore, as an accelerated model in analyzing the risk factors
      for cardiovascular diseases. We previously reported the role of blood pressure,
      one of the most important risk factors for cardiovascular diseases, in
      determining the prognosis of hemodialysis patients. In this study, we examined
      the effect of cardiomegaly detected on chest roentgenogram or electrocardiogram
      before initiating hemodialysis therapy on survival after introduction to
      maintenance hemodialysis. One hundred and sixty hemodialysis patients who had no
      history of ischemic heart disease or arrhythmia were followed up for 88.9 +/- 4.0
      months, among whom 69 died. Heart enlargement, defined on chest roentgenogram,
      was detected in 104 patients, and left ventricular hypertrophy, defined on
      electrocardiogram, was detected in 105 patients. The presence of either finding
      shortened their survival. However, Cox's proportional hazards model and logistic
      multiple regression analysis identified only left ventricular hypertrophy as one
      of the significant determinants for survival, but heart enlargement was not
      independent. Correction of systolic hypertension on the maintenance phase had no
      significant favorable effect on survival in patients with left ventricular
      hypertrophy, while it improved in those with heart enlargement. This finding,
      together with those above from Cox's model and logistic analysis strongly
      suggests that risk from left ventricular hypertrophy is independent of, but one
      from heart enlargement is dependent on hypertension.

PMID- 12071592
TI  - Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in
      hemodialysis, chronic ambulatory peritoneal dialysis and post-transplant
      patients.
AB  - Serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) apo(a)
      phenotypes were determined in 81 hemodialysis (HD) patients, 37 chronic
      ambulatory peritoneal dialysis (CAPD) patients, 25 post-transplant patients and
      99 healthy subjects as the reference group. The CAPD patients had significantly
      higher serum Lp(a) concentration than HD patients, but both had significantly
      increased Lp(a) levels as compared with the reference group and post-transplant
      patients. When all studied groups were divided into two subgroups with at least
      one low molecular weight (LMW) isoform and with only one high molecular weight
      (HMW) isoform, they presented a similar distribution. (Pearson's chi-squared =
      2,78; df = 3; p = NS). The median serum Lp(a) levels were significantly increased
      with HMW class versus the reference group and post-transplant patients. In CAPD
      patients, the LMW phenotypes showed significantly increased median serum Lp(a)
      concentrations versus the reference group, but they were not statistically
      elevated in HD patients. In the post-transplant patients, LMW and HMW phenotypes
      did not differ as compared to the reference group. The elevated Lp(a) levels in
      HD and CAPD groups were explained by apo(a) type-specific, but not by differences
      in, isoform frequencies. We conclude that HD and CAPD patients had increased
      Lp(a) levels compared with the reference group, whereas elevated Lp(a)
      concentrations were observed mainly in patients with HMW apo(a) phenotypes.
      Patients after renal transplantation showed a correction of Lp(a) levels mainly
      in HMW phenotypes. The LMW status corresponding to high Lp(a) levels and apo(a)
      isoforms could be used together with Lp(a) levels with other risk factors to
      assess in uremic patients the predisposition to coronary artery disease.

PMID- 12071593
TI  - Predialysis management and predictors for early mortality in uremic patients who
      die within one year after initiation of dialysis therapy.
AB  - Despite improvements in dialysis therapy, the mortality rate of patients with end
      stage renal disease (ESRD) has remained high. A relatively high proportion of
      uremic patients dies within one year after the initiation of dialysis treatment.
      The aim of this study was to evaluate predictors for this early mortality in
      patients with ESRD. A total of 66 uremic patients were included in the study.
      Patients were divided in those who survived < 1 year (n = 17) and those who
      survived > or = 1 year (n = 49). We compared the prevalence of diabetes and
      hypertension and of vascular diseases as well as the prevalence of heart
      insufficiency (EF < 30%) and left ventricular hypertrophy (LVH). Additionally, we
      estimated the laboratory parameters serum creatinine, creatinine clearance, BUN,
      cholesterol, triglycerides, fibrinogen, serum protein, serum albumin and
      hemoglobin, and evaluated the indications for the initiation of dialysis therapy
      in both patient groups. The patients with survival < 1 year were significantly
      older (64+/-12 vs. 54+/-14 years, p<0.01) and showed a lower BMI (22+/-3 vs. 25+/
      3, p<0.01) than those who survived > 1 year. The prevalence of diabetes (70% vs.
      31%, p<0.05), cardiac insufficiency (70% vs. 16%, p<0.025), cardiovascular
      disease (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%,
      p<0.05) was significantly higher in the patients with early mortality. The
      prevalence of hypertension was similar in both groups, however, the prevalence of
      LVH was significantly higher in the patients who survived < 1 year (88% vs. 37%,
      p<0.05). Laboratory parameters were not significantly different in the two groups
      of patients, with the exception of serum albumin, which was significantly lower
      in the patients with early mortality (3.5+/-0.6 vs. 3.9+/-0.4 g/l, p<0.02).
      Hyperhydration was the most common indication for the start of dialysis in
      patients with early mortality (59% vs. 13%, p<0.025). Cardiac insufficiency was
      the most common cause of death in these subjects (n = 10, 59%). Six individuals
      (12%) died within four weeks after initiating dialysis therapy. Thus, there are
      several predictors for early mortality in end-stage renal disease patients,
      including high age, low BMI, the presence of diabetes, coronary heart disease,
      heart insufficiency and LVH, as well as low serum albumin levels. A relatively
      high percentage of patients die shortly after the start of dialysis therapy.
      Heart insufficiency is the most common cause of early death in these patients.

PMID- 12071594
TI  - Twenty-four hour blood pressure profile and left ventricular hypertrophy early
      after renal transplantation.
AB  - BACKGROUND: Left ventricular hypertrophy is common in renal transplant patients
      but the factors influencing its development remain to be determined. The present
      investigation was conducted to study the effect of blood pressure load on the
      left ventricular mass of recently transplanted patients using 24-h ambulatory
      blood pressure monitoring (ABPM). METHODS: We studied 30 renal transplant (RT)
      patients (36.1+/-13.7 years old, 11 males, 26 Whites, 4 diabetics, 15 under
      antihypertensive medication, 21 recipients of cadaver donors, and all treated
      with steroids, cyclosporin and azathioprine and with adequate (serum creatinine <
      1.8 mg/100 ml) renal function). The median duration of dialysis treatment before
      transplant was 37 months, and the studies were performed during the first 40 days
      post-transplantation. Blood pressure was measured after a 15-min rest (casual
      blood pressure) and during a 24-h period with a SpaceLabs apparatus.
      Echocardiograms were obtained from all patients. RESULTS: Mean left ventricular
      mass index (LVMI) was 153+/-44 g/m2; casual systolic and diastolic BP (mmHg) was
      152+/-25 and 92+/-13, whereas systolic and diastolic 24-h BP was 133+/-12 and
      85+/-8, respectively. The systolic sleeping BP/awake systolic BP (SSBP/ASBP)
      ratio was 0.94+/-0.07, and 73% of the patients did not show a significant (>10%)
      fall of systolic blood pressure during sleep. Multivariate analysis showed that
      awake systolic blood pressure was the only variable that independently influenced
      LVMI after adjusting for confounding factors (regression coefficient = 0.49, p =
      0.01). Casual systolic and diastolic BP, sleeping systolic and diastolic blood
      pressure, 24-h heart rate, age, race, gender, smoking, body mass index, duration
      of dialysis, diabetes, antihypertensive and immunosuppressive drugs and levels of
      hematocrit, creatinine and serum lipids did not correlate with LVMI. CONCLUSION:
      The data indicate that left ventricular hypertrophy during the early post
      transplant period is mainly influenced by awake blood pressure load. They also
      suggest that ABPM may be more useful in the diagnosis and management of post
      transplant hypertension than casual BP. The findings emphasize the importance of
      rigid blood pressure control in renal transplant recipients.

PMID- 12071595
TI  - Homocysteine and vascular access thrombosis in hemodialysis patients.
AB  - BACKGROUND: Vascular access remains the Achilles' heel of successful
      hemodialysis, and thrombosis is the leading cause of vascular access failure.
      Hyperhomocystinemia is common in hemodialysis patients and is associated with
      venous and arterial thrombosis in patients without end-stage renal disease.
      SUBJECTS AND METHODS: In the study, 65 hemodialysis patients with native
      arteriovenous fistula were included. Two groups of patients were defined: group A
      including 45 patients with their vascular access either never or only once
      thrombosed, and group B including 20 patients with two or more thromboses of
      their vascular access. We determined serum concentrations of total homocysteine
      (immunoassay, Abbott) in our patients. RESULTS: In 63 (96.9%) patients,
      hyperhomocystinemia was presented. There was no statistically significant
      difference between group A and B regarding age, gender and duration of
      hemodialysis treatment. Total homocysteine concentrations were higher in group A
      (42.1 +/- 18.6 micromol/l) than in group B (36.1 +/- 18.1 micromol/l) patients
      but the difference was small and not statistically significant. CONCLUSION: We
      found no significant differences in total homocysteine concentrations between
      group A (thrombosis non-prone) and group B (thrombosis prone) patients. Our
      results suggest that thrombosis of native arteriovenous fistulas may not be
      caused by hyperhomocystinemia in these patients.

PMID- 12071596
TI  - Acute renal failure in the elderly: a five-year experience.

PMID- 12071597
TI  - Acute renal failure from spontaneous acute tumor lysis syndrome: a case report
      and review.
AB  - Acute tumor lysis syndrome (ATLS), a condition which results from a rapid
      destruction of tumor cells with massive release of cellular breakdown products,
      has been well described. However, only a few cases of spontaneous ATLS have been
      reported in the literature. Acute renal failure (ARF) from spontaneous ATLS has
      been reported only in three patients who were diagnosed to have Burkitt's
      lymphoma, adenocarcinoma, and acute myeloid leukemia. We report a similar case of
      a patient with non-Hodgkin's lymphoma, who developed ARF from spontaneous ATLS.
      ARF can complicate the clinical course of spontaneous ATLS. Since only one
      patient survived, patients who develop ARF from spontaneous ATLS have a poor
      outcome. This paper illustrates the need to anticipate the development of ARF,
      despite aggressive therapy, in a patient with spontaneous ATLS. Prospective
      studies on renal function prior to and during therapy are required in order to
      develop a clinical profile reliably detecting patients at risk for developing
      renal failure and subsequent complication.

PMID- 12071598
TI  - Large atrial septal aneurysm and delayed improvement of renal failure due to
      nephrotoxic drugs (and hemodialysis) in a diabetic patient.
AB  - Atrial septal aneurysm (ASA) is a well known morphologic abnormality and has been
      largely investigated with both transthoracic (TTE) and/or transesophageal
      echocardiography (TEE). Its association with other congenital and acquired heart
      diseases and midsystolic clicks has been reported. ASA also may be associated
      with an increased risk of embolic events. In many cases, it is an incidental
      finding. We describe a patient with acute renal failure associated with
      nephrotoxic drugs and ASA suggesting endocarditis.

PMID- 12071599
TI  - Spontaneous resolution of extensive periarticular metastatic calcification after
      renal transplant in a case of end stage renal disease.

PMID- 12071601
TI  - Controlled space closure with a statically determinate retraction system.
AB  - We designed a variant of a cantilever spring, the statically determinate
      retraction system, and studied its mechanical characteristics. This novel system
      consisted of a single-force cantilever arm made of 0.017 x 0.025-inch titanium
      molybdenum alloy wire for active retraction and a passive rigid stabilizing unit.
      Since the active component for space closure is a cantilever, it is simple to
      measure the force system of the spring with a force gauge (ie, the system is a
      statically determinate system). A torque tester apparatus was used to examine the
      property of this retraction spring with a helix at the posterior and a simple
      bend at the anterior. Both a standard shape and modified shapes of the spring
      were studied. At full activation, the standard spring delivered 163 g with a load
      deflection rate of six g/mm. When the magnitude of the anterior bend of the
      spring was increased, the horizontal component of the force increased more than
      the vertical component. In contrast, when the posterior bend of the spring
      increased, the vertical component of the force increased more than the horizontal
      component. A clinical case presented here clearly demonstrates the versatility
      and applicability of the spring.

PMID- 12071600
TI  - Low-dose intravenous iron administration in chronic hemodialysis patients treated
      with recombinant human erythropoietin.
AB  - We conducted a prospective study to determine the effect of intravenous low-dose
      iron administration in chronic hemodialysis patients treated with recombinant
      human erythropoietin (rHuEPO). Sixteen hemodialysis patients (8 males and 8
      females; mean age 63.1+/-9.8 years) on maintenance rHuEPO therapy were included
      in the study. Patients with <100 ng/ml of ferritin received 50 mg iron during
      every hemodialysis session. Patients with 100-200 ng/ml of ferritin were given 50
      mg iron fortnightly. Iron was not supplemented in patients with ferritin levels
      >200 ng/ml. Mean hematocrit, serum iron levels and transferrin saturations were
      significantly higher at 6 and 12 months. There was a significant reduction in
      weekly rHuEPO doses between the start and the 6th and 12th months. Our study
      shows intravenous iron administration of 100 mg/month may be sufficient to
      achieve a satisfactory iron status in dialysis patients on maintenance rHuEPO
      therapy.

PMID- 12071602
TI  - Effect of a fluoride-releasing self-etch acidic primer on the shear bond strength
      of orthodontic brackets.
AB  - Conventional adhesive systems use three different agents--an enamel conditioner,
      a primer solution, and an adhesive resin--during the bonding of orthodontic
      brackets to enamel. A unique characteristic of some new bonding systems in
      operative dentistry is that they combine the conditioning and priming agents into
      a single application. Combining conditioning and priming saves time and should be
      more cost-effective to the clinician and indirectly to the patient. The purpose
      of this study was to assess and compare the effects of self-etching primers,
      including a fluoride-releasing primer, on the shear bond strength of orthodontic
      brackets. The brackets were bonded to extracted human teeth according to one of
      four protocols. In group 1 (control), teeth were etched with 37% phosphoric acid;
      after the sealant was applied, the brackets were bonded with Transbond XT (3M
      Unitek, Monrovia, Calif) and light cured for 20 seconds. In group 2, a self-etch
      acidic primer (3M ESPE, St Paul, Minn) was applied as suggested by the
      manufacturer, and the brackets were then bonded with Transbond XT as in the first
      group. In group 3, an experimental self-etch primer EXL #547 (3M ESPE) was
      applied to the teeth as suggested by the manufacturer, and the brackets were then
      bonded as in groups 1 and 2. In group 4, a fluoride-releasing self-etch primer,
      One-Up Bond F (J. Mortia, USA Inc. Irvine, Calif) that also has a novel dye
      sensitized photo polymerization initiator system was applied as suggested by the
      manufacturer, and the brackets were then bonded as in the other groups. The
      present in vitro findings indicated that the shear bond strengths of the four
      groups were significantly different (P = .001). Duncan multiple range tests
      indicated that One-Up Bond F (mean +/- SD strength, 5.1+/-2.5 MPa) and Prompt L
      Pop (strength, 7.1+/-4.4 MPa) had significantly lower shear bond strengths than
      both the EXL #547 self-etch primer (strength, 9.7+/-3.7 MPa) or the phosphoric
      acid etch and the conventional adhesive system (strength, 10.4+/-2.8 MPa).

PMID- 12071603
TI  - A cephalometric study of the Class II correction effects of the Eureka Spring.
AB  - The effect of the Eureka Spring (ES) appliance was investigated on 37
      consecutively treated, noncompliant patients with bilateral Class II
      malocclusions. Lateral cephalographs were taken at the start of orthodontic
      treatment (T1), at insertion of the ES (T2), and at removal of the ES (T3). The
      average treatment interval between T2 and T3 was four months. The Class II
      correction occurred almost entirely by dentoalveolar movement and was almost
      equally distributed between the maxillary and mandibular dentitions. The rate of
      molar correction was 0.7 mm/mo. There was no change in anterior face height,
      mandibular plane angle, palatal plane angle, or gonial angle with treatment.
      There was a 2 degrees change in the occlusal plane resulting from intrusion of
      the maxillary molar and the mandibular incisor. Based on the results in this
      sample, the ES appliance was very effective in correcting Class II malocclusions
      in noncompliant patients without increasing the vertical dimension.

PMID- 12071604
TI  - The role of nitric oxide in orthodontic tooth movement in rats.
AB  - Nitric oxide (NO) is involved in second messenger formation, osteoblast and
      osteoclast function, and pulpal blood flow. This raises the question of whether
      or not altered NO production interferes with orthodontic tooth movement (OTM) by
      influencing the bone remodeling cycle. To investigate the role of NO in OTM, a
      rat model was established and 48 rats were divided into four study groups of 12
      rats each. A 5 mm nickel-titanium closed-coil spring was ligated between the
      right maxillary incisor and first molar of each rat to deliver an initial force
      of 60 g. A saline group received subperiosteal injections of normal saline (50
      microL/kg), an L-arginine (L-arg) group received L-arginine (NO precursor)
      injections (200 mg/kg), and a, L-NAME group received N(G)-nitro-L-arginine methyl
      ester (nitric oxide synthase inhibitor)(10 mg/kg) injections. All injections were
      given in the upper right first molar mucosa from the first through the 11th day
      of force application at 48-hour intervals. A control group received no
      injections. Tooth movement measurements were done at the time of injections.
      Animals were sacrificed 13 days after appliance insertion and final OTMs were
      measured at the time of sacrifice. From the third day till the end of the
      experiment, the L-arg group showed a significant increase in tooth movements,
      whereas the L-NAME group showed a significant decrease in tooth movements
      compared to the control and saline group (P < .001). Histopathologic studies
      revealed that the number of osteoclasts was significantly higher in the L-arg
      group smears, while the number of osteoclasts in the L-NAME group was
      significantly lower as compared to the control group (P < .001). Scanning
      electron microscope analysis showed that the force-induced root resorption in the
      L-arg group was less than the control group. This study suggests a role for NO in
      the bone remodeling cycle.

PMID- 12071605
TI  - New regression equations for predicting the size of unerupted canines and
      premolars in a contemporary population.
AB  - The determination of a tooth-size to arch-length discrepancy in the mixed
      dentition requires an accurate prediction of the mesiodistal widths of the
      unerupted permanent teeth. This is an essential factor in treatment planning. The
      aim of this study was to validate Tanaka and Johnston's analysis on 600 Syrian
      patients aged 14-22 years. Tanaka and Johnston's tables, equations, and
      approximations were modified in order to improve the accuracy of the prediction.
      The correlation coefficients found between the size of the permanent mandibular
      central incisors and maxillary first molars (31, 41, 16, and 26) and the
      maxillary and mandibular canines and premolars were high (r = .72 and .74,
      respectively). New, more accurate prediction tables applicable at earlier ages,
      and new regression equations were constructed. In addition, new easier
      approximations were developed to allow the prediction of the size of the
      unerupted maxillary canines and premolars by adding 6 mm to the half-widths of
      teeth 31, 41, 16, and 26. The analogous prediction of the size of the unerupted
      mandibular canines and premolars was obtained by adding 5.5 mm to the half-widths
      of same teeth, 31, 41, 16, and 26.

PMID- 12071606
TI  - In vivo aging of orthodontic alloys: implications for corrosion potential, nickel
      release, and biocompatibility.
AB  - Despite the large number of studies investigating nickel release from orthodontic
      stainless steel and nickel-titanium alloys, there is a lack of conclusive
      evidence with respect to the composition and kinetics of the corrosive products
      released. The objective of this review is to address the critical issues of
      corrosion potential and nickel leaching from alloys by investigating the effect
      of intraoral conditions on the surface reactivity of the materials. After an
      overview of fundamentals of metallurgical structure of orthodontic alloys, we
      provide an analysis of corrosion processes occurring in vivo. We present recent
      evidence suggesting the formation of a proteinaceous biofilm on retrieved
      orthodontic materials that later undergoes calcification. We illustrate the
      vastly irrelevant surface structure of in vivo- vs in vitro-aged alloys and
      discuss the potential implications of this pattern in the reactivity of the
      materials. Finally, we present a comprehensive review of the issue of nickel
      release, based on three perspectives: its biologic effects, the methods used for
      studying its release, and nickel-induced hypersensitivity in orthodontic
      patients.

PMID- 12071607
TI  - Correlation between mandibular central incisor proclination and gingival
      recession during fixed appliance therapy.
AB  - The purpose of this study was to determine whether proclination of mandibular
      central incisors during fixed appliance therapy results in gingival recession.
      Complete records of 67 patients (39 female and 28 male patients; mean age, 16.4
      years; age range, 10-45 years) were used in this retrospective case-control
      study. Using pretreatment and posttreatment lateral cephalograms, the change in
      mandibular central incisor inclination was measured to divide the patients into
      an experimental group (proclination) and a control group (no proclination).
      Changes in clinical crown length were determined from pretreatment and
      posttreatment study models, and changes in gingival recession were determined
      from intraoral slides. Eight of the 67 patients exhibited a measurable increase
      in gingival recession of at least 0.5 mm, and 27 patients had an increase in
      clinical crown length of at least 0.5 mm. Statistical analyses showed no
      correlation between mandibular central incisor proclination and gingival
      recession or clinical crown length. A t-test analysis showed no statistically
      significant difference in gingival recession or change in clinical crown length
      between patients whose mandibular central incisors were proclined and those whose
      incisors were not proclined. Multiple regression analysis demonstrated that age,
      sex, race, treatment duration, extraction, treatment type, Angle classification,
      and proclination were not related to gingival recession or change in clinical
      crown length of mandibular central incisors. We conclude that the degree of
      proclination of mandibular central incisors during fixed appliance therapy was
      not correlated to gingival recession in this sample.

PMID- 12071608
TI  - Longitudinal cephalometric changes in incisor position, overjet, and overbite
      between 10 and 14 years of age.
AB  - The purpose of this study was to evaluate the longitudinal growth changes in the
      incisor position, overjet, and overbite between 10 and 14 years of age. Serial
      cephalometric radiographs of 63 subjects (31 boys and 32 girls) were taken at the
      ages of 10, 11, 12, and 14. The effects of age and gender on the incisor
      positions, overjet, and overbite were investigated by means of variance analysis
      and least square difference (LSD) tests. The results show that the measurements
      of overbite, upper incisor-NA (mm), lower incisor-NB (mm), upper incisor-NA
      (angle), and the interincisal angle were affected by age. The results also show
      that the measurements of overbite, upper incisor-NA (mm), upper incisor-NA
      (angle) and upper incisor-SN (angle) were affected by gender.

PMID- 12071609
TI  - Pathognomonic cephalometric characteristics of Angle Class II Division 2
      malocclusion.
AB  - The Class II division 2 (Class II/2) malocclusion as originally defined by E.H.
      Angle is relatively rare. The orthodontic literature does not agree on the
      skeletal characteristics of this malocclusion. Several researchers claim that it
      is characterized by an orthognathic facial pattern and that the malocclusion is
      dentoalveolar per se. Others claim that the Class II/2 malocclusion has unique
      skeletal and dentoalveolar characteristics. The present study describes the
      skeletal and dentoalveolar cephalometric characteristics of 50 patients
      clinically diagnosed as having Class II/2 malocclusion according to Angle's
      original criteria. The study compares the findings with those of both a control
      group of 54 subjects with Class II division I (Class II/1) malocclusion and a
      second control group of 34 subjects with Class I (Class I) malocclusion. The
      findings demonstrate definite skeletal and dentoalveolar patterns with the
      following characteristics: (1) the maxilla is orthognathic, (2) the mandible has
      relatively short and retrognathic parameters, (3) the chin is relatively
      prominent, (4) the facial pattern is hypodivergent, (5) the upper central
      incisors are retroclined, and (6) the overbite is deep. The results demonstrate
      that, in a sagittal direction, the entity of Angle Class II/2 malocclusion might
      actually be located between the Angle Class I and the Angle Class II/1
      malocclusions. with unique vertical skeletal characteristics.

PMID- 12071610
TI  - Changes in articular eminence inclination during the craniofacial growth period.
AB  - The articular eminence of the temporomandibular joint dictates the path and type
      of condylar-disk complex movement. It has been suggested that a steep articular
      eminence inclination may predispose to temporomandibular joint dysfunction. When
      using functional appliances in orthodontic therapy, the bite registration is
      greatly affected by the articular eminence inclination. Furthermore, the
      articular eminence morphology has been related to specific facial types.
      Knowledge of how the articular eminence inclination behaves during the
      craniofacial growth period could help establish more biological treatment
      modalities. We took silicone impressions of both left and right articular fossae
      from 90 dried skulls. This sample consisted of three equal subgroups of skulls,
      each group presenting a deciduous, mixed, or permanent dentition. After the
      impression had set, they were removed and cut into sagittal sections 2.5 mm
      thick. The three middle sections were photocopied and enlarged by 200%. The
      inclination of each section was calculated trigonometrically, and the mean value
      was assigned to the inclination of the respective eminence. The data indicated
      that the inclination of the articular eminence changes rapidly until the
      completion of deciduous dentition, attaining more or less 45% of its adult value.
      By the age of 10 years, it was 70%-72% completed, and by the age of 20 years, it
      was 90%-94% completed. In conclusion, normally, the articular eminence
      inclination shows a symmetrical growth pattern, and it grows at a very rapid
      rate, attaining almost half of its adult value by the age of two years.

PMID- 12071611
TI  - Correction of severe vertical maxillary excess with anterior open bite and
      transverse maxillary deficiency.
AB  - Patients requiring correction of large anterior open bites have historically been
      among the most challenging treatments for orthodontists. Adding to that
      fundamental challenge for the adult patient in this case was vertical maxillary
      excess, a severe transverse maxillary deficiency as well as an arch length
      inadequacy, even though the patient had prior orthodontic treatment. The prior
      orthodontist had included arch expansion and extracted four first bicuspids,
      which limited current treatment options. Various treatment modalities that have
      traditionally been used to correct transverse maxillary deficiency and the
      accompanying arch length inadequacy include extractions, labial and buccal dental
      tipping, segmental maxillary osteotomies, and rapid maxillary expansion with or
      without surgical assistance. Transverse maxillary distraction osteogenesis is a
      modification (ie, using a latency period and specific rate and rhythm of
      distraction) of the surgically assisted rapid maxillary expansion technique
      developed 25 years ago. This case demonstrates the relationship of transverse
      maxillary deficiency as well as vertical maxillary excess to apertognathia.
      Considerations regarding the use of segmental maxillary osteotomy vs transverse
      distraction osteogenesis are discussed. This case report illustrates the benefit
      of a team approach using transverse maxillary distraction osteogenesis, effective
      orthodontic mechanics, and orthognathic surgery to correct a severe dentofacial
      deformity.

PMID- 12071612
TI  - An orthodontic case of transposition of the upper right canine and first
      premolar.
AB  - Tooth transposition is a rare and severe positional anomaly that may create many
      orthodontic problems from both esthetic and functional points of view. In this
      report, we describe a case of the orthodontic management of a transposition of
      the upper canine and premolar with congenital absence of the upper lateral
      incisor. The patient was treated with a multibracket appliance and the extraction
      of three premolars, and treatment was completed without a need for any prosthetic
      replacement.

PMID- 12071613
TI  - Ethics and economics.

PMID- 12071614
TI  - Optimal shifted estimates of human-observer templates in two-alternative forced
      choice experiments.
AB  - For performing simple detection and discrimination tasks in image noise, human
      observers are often modeled by a cross-correlation between the image and an
      observer template followed by the injection of the observer's internal noise.
      This paper is concerned with estimating this template using the two-alternative
      forced-choice (2AFC) experimental paradigm. The basic idea behind the estimation
      procedure is to average the noise fields of the images used in a 2AFC experiment
      with a weight that depends on whether the observer got the trial correct or
      incorrect. We describe a method that produces unbiased estimates of the observer
      template up to a constant of proportionality under the linear cross-correlation
      model. The method proposed here is different from some previous methods in the
      way it assigns weights to the noise fields and we show that the resulting errors
      in the estimated template are minimized. We also propose and validate a formula
      for approximating the error covariance associated with the template estimates.

PMID- 12071615
TI  - Objective comparison of quantitative imaging modalities without the use of a gold
      standard.
AB  - Imaging is often used for the purpose of estimating the value of some parameter
      of interest. For example, a cardiologist may measure the ejection fraction (EF)
      of the heart in order to know how much blood is being pumped out of the heart on
      each stroke. In clinical practice, however, it is difficult to evaluate an
      estimation method because the gold standard is not known, e.g., a cardiologist
      does not know the true EF of a patient. Thus, researchers have often evaluated an
      estimation method by plotting its results against the results of another (more
      accepted) estimation method, which amounts to using one set of estimates as the
      pseudogold standard. In this paper, we present a maximum-likelihood approach for
      evaluating and comparing different estimation methods without the use of a gold
      standard with specific emphasis on the problem of evaluating EF estimation
      methods. Results of numerous simulation studies will be presented and indicate
      that the method can precisely and accurately estimate the parameters of a
      regression line without a gold standard, i.e., without the x axis.

PMID- 12071616
TI  - Consistent landmark and intensity-based image registration.
AB  - Two new consistent image registration algorithms are presented: one is based on
      matching corresponding landmarks and the other is based on matching both landmark
      and intensity information. The consistent landmark and intensity registration
      algorithm produces good correspondences between images near landmark locations by
      matching corresponding landmarks and away from landmark locations by matching the
      image intensities. In contrast to similar unidirectional algorithms, these new
      consistent algorithms jointly estimate the forward and reverse transformation
      between two images while minimizing the inverse consistency error-the error
      between the forward (reverse) transformation and the inverse of the the reverse
      (forward) transformation. This reduces the ambiguous correspondence between the
      forward and reverse transformations associated with large inverse consistency
      errors. In both algorithms a thin-plate spline (TPS) model is used to regularize
      the estimated transformations. Two-dimensional (2-D) examples are presented that
      show the inverse consistency error produced by the traditional unidirectional
      landmark TPS algorithm can be relatively large and that this error is minimized
      using the consistent landmark algorithm. Results using 2-D magnetic resonance
      imaging data are presented that demonstrate that using landmark and intensity
      information together produce better correspondence between medical images than
      using either landmarks or intensity information alone.

PMID- 12071617
TI  - Local frequency representations for robust multimodal image registration.
AB  - Automatic registration of multimodal images involves algorithmically estimating
      the coordinate transformation required to align the data sets. Most existing
      methods in the literature are unable to cope with registration of image pairs
      with large nonoverlapping field of view (FOV). We propose a robust algorithm,
      based on matching dominant local frequency image representations, which can cope
      with image pairs with large nonoverlapping FOV. The local frequency
      representation naturally allows for processing the data at different
      scales/resolutions, a very desirable property from a computational efficiency
      view point. Our algorithm involves minimizing-over all rigid/affine
      transformations--the integral of the squared error (ISE or L2 E) between a
      Gaussian model of the residual and its true density function. The residual here
      refers to the difference between the local frequency representations of the
      transformed (by an unknown transformation) source and target data. We present
      implementation results for image data sets, which are misaligned magnetic
      resonance (MR) brain scans obtained using different image acquisition protocols
      as well as misaligned MR-computed tomography scans. We experimently show that our
      L2E-based scheme yields better accuracy over the normalized mutual information.

PMID- 12071618
TI  - What is the best similarity measure for motion correction in fMRI time series?
AB  - It has been shown that the difference of squares cost function used by standard
      realignment packages (SPM and AIR) can lead to the detection of spurious
      activations, because the motion parameter estimations are biased by the activated
      areas. Therefore, this paper describes several experiments aiming at selecting a
      better similarity measure to drive functional magnetic resonance image
      registration. The behaviors of the Geman-McClure (GM) estimator, of the
      correlation ratio, and of the mutual information (MI) relative to activated areas
      are studied using simulated time series and actual data stemming from a 3T
      magnet. It is shown that these methods are more robust than the usual difference
      of squares measure. The results suggest also that the measures built from robust
      metrics like the GM estimator may be the best choice, while MI is also an
      interesting solution. Some more work, however, is required to compare the various
      robust metrics proposed in the literature.

PMID- 12071619
TI  - Using replicator dynamics for analyzing fMRI data of the human brain.
AB  - The understanding of brain networks becomes increasingly the focus of current
      research. In the context of functional magnetic resonance imagery (fMRI) data of
      the human brain, networks have been mostly detected using standard clustering
      approaches. In this work, we present a new method of detecting functional
      networks using fMRI data. The novelty of this method is that these networks have
      the property that every network member is closely connected with every other
      member. This definition might to be better suited to model important aspects of
      brain activity than standard cluster definitions. The algorithm that we present
      here is based on a concept from theoretical biology called "replicator dynamics."

PMID- 12071620
TI  - Spatiotemporal forward solution of the EEG and MEG using network modeling.
AB  - Dynamic systems have proven to be well suited to describe a broad spectrum of
      human coordination behavior such synchronization with auditory stimuli.
      Simultaneous measurements of the spatiotemporal dynamics of
      electroencephalographic (EEG) and magnetoencephalographic (MEG) data reveals that
      the dynamics of the brain signals is highly ordered and also accessible by
      dynamic systems theory. However, models of EEG and MEG dynamics have typically
      been formulated only in terms of phenomenological modeling such as fixed-current
      dipoles or spatial EEG and MEG patterns. In this paper, it is our goal to connect
      three levels of organization, that is the level of coordination behavior, the
      level of patterns observed in the EEG and MEG and the level of neuronal network
      dynamics. To do so, we develop a methodological framework, which defines the
      spatiotemporal dynamics of neural ensembles, the neural field, on a sphere in
      three dimensions. Using magnetic resonance imaging we map the neural field
      dynamics from the sphere onto the folded cortical surface of a hemisphere. The
      neural field represents the current flow perpendicular to the cortex and, thus,
      allows for the calculation of the electric potentials on the surface of the skull
      and the magnetic fields outside the skull to be measured by EEG and MEG,
      respectively. For demonstration of the dynamics, we present the propagation of
      activation at a single cortical site resulting from a transient input. Finally, a
      mapping between finger movement profile and EEG/MEG patterns is obtained using
      Volterra integrals.

PMID- 12071621
TI  - Estimating distributed anatomical connectivity using fast marching methods and
      diffusion tensor imaging.
AB  - A method is presented for determining paths of anatomical connection between
      regions of the brain using magnetic resonance diffusion tensor information. Level
      set theory, applied using fast marching methods, is used to generate three
      dimensional time of arrival maps, from which connection paths between brain
      regions may be identified. The method is demonstrated in the normal brain and it
      is shown that major white matter tracts may be elucidated and that multiple
      connections and tract branching are allowed. Maps of connectivity between brain
      regions are also determined. Four options are described for estimating the degree
      of connectivity between regions.

PMID- 12071622
TI  - Using a statistical shape model to extract sulcal curves on the outer cortex of
      the human brain.
AB  - A method for automated segmentation of major cortical sulci on the outer brain
      boundary is presented, with emphasis on automatically determining point
      correspondence and on labeling cortical regions. The method is formulated in a
      general optimization framework defined on the unit sphere, which serves as
      parametric domain for convoluted surfaces of spherical topology. A statistical
      shape model, which includes a network of deformable curves on the unit sphere,
      seeks geometric features such as high curvature regions and labels such features
      via a deformation process that is confined within a spherical map of the outer
      brain boundary. The limitations of the customary spherical coordinate system,
      which include discontinuities at the poles and nonuniform sampling, are overcome
      by defining the statistical prior of shape variation in terms of projections of
      landmark points onto corresponding tangent planes of the sphere. The method is
      tested against and shown to be as accurate as manually defined segmentations.

PMID- 12071623
TI  - A minimum description length approach to statistical shape modeling.
AB  - We describe a method for automatically building statistical shape models from a
      training set of example boundaries/surfaces. These models show considerable
      promise as a basis for segmenting and interpreting images. One of the drawbacks
      of the approach is, however, the need to establish a set of dense correspondences
      between all members of a set of training shapes. Often this is achieved by
      locating a set of "landmarks" manually on each training image, which is time
      consuming and subjective in two dimensions and almost impossible in three
      dimensions. We describe how shape models can be built automatically by posing the
      correspondence problem as one of finding the parameterization for each shape in
      the training set. We select the set of parameterizations that build the "best"
      model. We define "best" as that which minimizes the description length of the
      training set, arguing that this leads to models with good compactness,
      specificity and generalization ability. We show how a set of shape
      parameterizations can be represented and manipulated in order to build a minimum
      description length model. Results are given for several different training sets
      of two-dimensional boundaries, showing that the proposed method constructs better
      models than other approaches including manual landmarking-the current gold
      standard. We also show that the method can be extended straightforwardly to three
      dimensions.

PMID- 12071624
TI  - Multiscale deformable model segmentation and statistical shape analysis using
      medial descriptions.
AB  - This paper presents a multiscale framework based on a medial representation for
      the segmentation and shape characterization of anatomical objects in medical
      imagery. The segmentation procedure is based on a Bayesian deformable templates
      methodology in which the prior information about the geometry and shape of
      anatomical objects is incorporated via the construction of exemplary templates.
      The anatomical variability is accommodated in the Bayesian framework by defining
      probabilistic transformations on these templates. The transformations, thus,
      defined are parameterized directly in terms of natural shape operations, such as
      growth and bending, and their locations. A preliminary validation study of the
      segmentation procedure is presented. We also present a novel statistical shape
      analysis approach based on the medial descriptions that examines shape via
      separate intuitive categories, such as global variability at the coarse scale and
      localized variability at the fine scale. We show that the method can be used to
      statistically describe shape variability in intuitive terms such as growing and
      bending.

PMID- 12071626
TI  - Fool-proof adhesives?

PMID- 12071625
TI  - The nanoleakage phenomenon: influence of moist vs dry bonding.
AB  - PURPOSE: To assess the degree of nanoleakage of Class V preparations restored
      with three bonding agents using wet and dry bonding. MATERIALS AND METHODS:
      Standardized Class V cavities were prepared in 66 human molars with cervical
      margins located in dentin. The composite was placed using one of three different
      dentin bonding agents with a moist or dry bonding technique (n = 11 per group).
      The teeth were stored in a 1% rhodamin-B solution for 24 h at 20 degrees C, then
      rinsed with water, embedded in methacrylate, and sectioned parallel to the long
      axis of the tooth, separating the restorations into two parts. A confocal laser
      scanning microscope (CLSM) was used to visualize the layer 10 microm under the
      prepared surface of the section. The lengths of the dye-penetrated pathways were
      measured, representing the amount of nanoleakage. RESULTS: Differences in
      nanoleakage between the tested materials were proven to be statistically
      significant. The effect of drying had a significant influence on both the acetone
      based and the ethanol-based material, but not on the water-based bonding resin.
      CONCLUSION: Dentin drying may have an influence on nanoleakage, depending upon
      the nature of the individual bonding agent.

PMID- 12071627
TI  - The in vitro dentin bond strengths of two adhesive systems in class I cavities of
      human molars.
AB  - PURPOSE: The purpose of this study was to evaluate the in vitro dentin bond
      strengths of two dentin bonding systems in Class I cavities following fatigue
      load cycling (FLC) with thermal cycling (TC). MATERIALS AND METHODS: Class I
      cavities were prepared in 12 human molars and restored with either Clearfil SE
      Bond (SE) and Clearfil AP-X resin composite (AP-X) or Single Bond (SB)/AP-X
      according to the manufacturers' instructions. After water storage for 1 week,
      untreated controls and test samples were subjected to 50,000 FLC with TC from 5
      degrees C to 55 degrees C for 625 cycles and stored in water for 1 week.
      Microtensile bond strength (MTBS) tests were measured on the floor of the
      cavities at a crosshead speed of 1 mm/min. Data were statistically analyzed using
      one- and two-way ANOVA and Fisher's PLSD test at a 5% level of significance.
      RESULTS: The MPa results were: SE 30.5+/-12.8 (control) and 23.2+/-10.8 (50,000
      FLC); SB 5.1+/-9.2 (control) and 4.7+/-5.7 (50,000 FLC). Bond strengths were not
      statistically significantly affected by FLC (p > 0.05); however, they were
      influenced by the bonding system (p < 0.05). The MTBS of SE was significantly
      higher than that of SB (p < 0.05) under FLC and TC test conditions. Over half of
      the SB specimens debonded during sample preparation, showing blister-like
      structures, suggesting that an over-wet phenomenon occurred on the cavity floor.
      CONCLUSION: SE produced excellent dentin bonds that were much stronger than those
      produced by SB, which was shown to be a technique-sensitive bonding system.

PMID- 12071628
TI  - Depth of cure efficacy of high-power curing devices vs traditional halogen lamps.
AB  - PURPOSE: To determine the depth of cure resulting from three different curing
      devices in a photoactivated microhybrid composite through high-performance liquid
      chromatography (HPLC) analysis of leachable monomers. MATERIALS AND METHODS:
      Three different curing units, a halogen lamp (Heliolux, Vivadent), a xenon lamp
      (Kreative Kuring, Allyn Welch), and a plasma-arc lamp (Apollo 95, DMDS) were
      investigated using a universal microhybrid composite (P 60, 3M) as the test
      material. To assess the effect of curing device variation, a flexural strength
      test was performed. In addition, samples of composite were prepared and cured "in
      contact" (0 mm between the sample surface and light-guide tip) and through a
      specific thickness of composite (1, 2, or 3 mm). The monomers (bis-GMA and UDMA)
      eluted from the samples were detected by HPLC. RESULTS: No significant
      differences were found in the mechanical properties of composite cured with
      different light sources. In contrast, the concentration of eluted monomers (bis
      GMA, UDMA) at a depth of 2 mm and more was significantly higher for the specimens
      cured with the high-power curing devices than those cured with the traditional
      halogen lamp. CONCLUSION: Under these experimental conditions, high-power curing
      devices were shown to be inferior in the deep polymerization of resin composite
      when compared to a traditional halogen lamp.

PMID- 12071630
TI  - The influence of hygroscopic expansion of resin-based restorative materials on
      artificial gap reduction.
AB  - PURPOSE: This study compared the effect of water sorption on the extent of
      marginal gap reduction in two resin-modified glass-ionomer cements (RMGICs), two
      giomers, two compomers, and two resin composites over a twelve-week storage
      period. MATERIALS AND METHODS: Artificial gaps were created in 160 borosilicate
      glass cylinders. One-half of the internal surface of each cylinder was blocked
      out with wax and the other half was sandblasted. The bonding surface was further
      treated with 4% hydrofluoric acid, rinsed, and then coated with silane. After
      removal of the wax, one coat of dentin adhesive was applied to the silane-treated
      surface of the cylinder, briefly air dried and light cured. Eight light-cured
      restorative materials were placed incrementally: Vitremer (V), Fuji II LC (FJ),
      Beautifil (B), Reactmer Paste (R), Compoglass F (C), F2000 (F), Filtek Z250 (Z),
      and Tetric-Ceram (T). For each material, ten specimens were stored in deionized
      water (W), and ten (control) in nonaqueous silicone fluid (O) at 37 degrees C.
      The dimension of the same maximum gap created in each specimen was repeatedly
      measured at 0, 1, 2, 4, 6, 8, 10, and 12 weeks. RESULTS: R-W exhibited extensive
      hygroscopic expansion that resulted in cracking of 40% of glass cylinders after
      the 2nd week and 70% after the 4th week. One-way ANOVA of the other seven water
      groups showed significant differences (p < 0.001) among gap widths measured at
      different time intervals in V-W, FJ-W, C-W, F-W. Both RMGICs had the most
      significant gap reduction during the first week (p < 0.001). Both compomers
      exhibited delayed water-sorption characteristics, with more significant gap
      reduction observed in C-W. B-W was similar to the two resin composites Z-W and T
      W and exhibited the least gap reduction. After the first week, there were no
      significant differences in the percentage reduction in marginal gaps for any of
      the groups (p > 0.05). CONCLUSION: Marginal gap reduction that results from water
      sorption is more extensive and rapid in RMG-ICs, followed by compomers, whereas
      composites are relatively stable. Reactmer Paste exhibits rapid and extensive
      expansion and should probably be avoided in tooth preparations that involve thin
      unsupported enamel.

PMID- 12071631
TI  - Are adhesive technologies needed to support ceramics? An assessment of the
      current evidence.
AB  - Despite large variations in the reported fracture strengths of dispersion
      strengthened, glass infiltrated, castable, pressable and machinable ceramics
      utilised for the construction of all-ceramic crowns, the annual clinical failure
      rate reported for these materials in the dental literature is remarkably
      consistent at ca 3%. These results emphasise that there may be little correlation
      between the average fracture strength and resultant clinical performance.
      Consequently, if ceramics are to be used for dental applications, then clearly
      more detailed information on the statistical variations in strength combined with
      the influence of cementation media are required. The effect of adhesive
      technology has been examined in laboratory and clinical studies. The laboratory
      studies focused on the effect of cement lute on crown performance, whilst surface
      degradation and strengthening effects with different systems were examined
      utilising conventional materials science techniques. Clinical studies focused on
      the failure rates of conventionally luted and adhesively luted crowns and inlays.
      There would appear to be evidence from clinical studies that crowns luted with a
      resin cement and with the placement procedure incorporating a dentine bonding
      stage have enhanced rates of survival. It is therefore concluded that the
      available research strongly suggests that the use of resin as a luting material
      for ceramic restorations is indicated, given the research from three differing
      sources - laboratory fracture studies comparing restorations luted with resin vs
      other materials, clinical studies, and laboratory studies examining the surface
      sealing/strengthening effect of resin on ceramic. Laboratory studies also confirm
      the enhanced resistance to fracture of crowns cemented with an adhesive
      procedure.

PMID- 12071629
TI  - Durability of the dual-cure resin cement/ceramic bond with different curing
      strategies.
AB  - PURPOSE: To evaluate the effects of different curing strategies on the durability
      of the dual-cure resin cement/ceramic bond. MATERIALS AND METHODS: Machinable
      ceramic blanks were cut into pairs of 3-mm-thick slices, which were then polished
      using wet 600-grit SiC paper. The slices were silanated using one of two ceramic
      priming systems: (1) Tokuso Ceramic Primer (TCP), and (2) K-etchant/Clearfil
      Liner Bond 2V Primer (LB2V)/Porcelain Bond Activator (PBA), and bonded with one
      of two dual-cure resin cements (Bistite II, Panavia F), to make four experimental
      groups. Each group was subjected to one of three curing strategies: (1) no light,
      (2) 20 s light exposure from one direction, and (3) 20 s light exposure from each
      of six directions. After 24 h water storage at 37 degrees C, 0.7-mm-thick slabs
      were produced by serially sectioning perpendicular to the bonded interface.
      Immediately thereafter, and after one and six weeks of water storage, two slabs
      were randomly selected and sliced into beams for the microtensile bond strength
      (microTBS) test. Data were evaluated using Kruskal-Wallis and Wilcoxon rank tests
      (p < 0.05), and failure modes determined using a laser-scanning confocal
      microscope. RESULTS: After priming with TCP, microTBS of Bistite II significantly
      increased over time when exposed to light, whereas the microTBS of the no-light
      group significantly decreased over time (p < 0.05). After priming with TCP,
      microTBS of Panavia F increased over time, and after 6 weeks water storage, there
      were no significant differences in microTBS between the no-light and light
      exposed groups (p > 0.05). Increases in microTBS were associated with increases
      in the number of cohesive failures in resin cement. After phosphoric acid
      treatment, priming with LB2V/PBA, and light exposure, microTBS of Bistite II
      remained stable, whereas that of Panavia F significantly reduced over time (p <
      0.05). The microTBS of no-light LB2V/PBA groups reduced significantly over time
      (p < 0.05). CONCLUSION: The durability of the dual-cure resin cement/ceramic bond
      depends upon the multicomponent ceramic primer and the amount of light received
      by the resin cement.

PMID- 12071632
TI  - Mechanical properties and bond strength of glass-ionomer cements.
AB  - PURPOSE: The objective of this study was to evaluate the mechanical properties
      and bond strength of glass-ionomer cements (GICs) and resin-modified GICs (RM
      GICs) that are indicated as restorative materials for the Atraumatic Restorative
      Treatment (ART) technique. MATERIALS AND METHODS: Fifteen disk specimens for the
      diametral tensile strength (DTS) test and fifteen cylindrical specimens for the
      compressive strength (CS) test were made of each GIC: Ketac-Fil, Ketac-Molar
      (ESPE), Fuji IX and Fuji PLUS (GC). Forty human molars were sectioned and
      embedded in resin with either buccal or lingual surfaces exposed for the tensile
      bond strength (TBS) test. The surface was ground until a flattened area of enamel
      or dentin was obtained. After conditioning, inverted truncated cones of GICs were
      prepared on the flat tooth surfaces. The powder:liquid ratio of Fuji PLUS was
      adjusted for restorative purposes. Prior to testing, specimens were stored for 24
      h (TBS test) and for 1 h, 24 h, and 7 days (CS and DTS tests) in deionized water
      at 37 degrees C. They were then loaded at a crosshead speed of 1.0 mm/min for CS
      and 0.5 mm/min for DTS and TBS tests until failure occurred. The data were
      submitted to two-way ANOVA at 0.05 level of significance, followed by a Tukey
      Kramer test for multiple comparisons. RESULTS: The mean CS values ranged from
      90.27 to 170.73 MPa and DTS means from 6.21 to 22.32, with test periods from 1 h
      to 7 days. The means for TBS ranged from 4.90 to 11.36 MPa and from 2.52 to 5.55
      MPa in enamel and dentin, respectively. No differences were found between
      materials with the CS test except at 1 hour. The resin-modified GIC (RM-GIC) had
      the highest DTS, with no changes between the test periods, and the highest TBS
      for both enamel and dentin. CONCLUSION: Among the GICs tested, RM-GIC showed
      higher values of DTS and TBS.

PMID- 12071633
TI  - Cell proliferation and tumors of the central nervous system. Part 1: Evaluation
      of mitotic activity.
AB  - Evaluation of cell proliferation has been long recognized in pathology as a
      mainstay of diagnosis and important in the prognostication of a variety of
      neoplasms. Routine light microscopic evaluation of mitotic activity has long
      served as a reasonable assessment of cell proliferation. Counting mitotic figures
      has the advantage of being inexpensive and relatively quick. The main objections
      leveled against utilization of mitosis counts in diagnostic decision making are
      related to the instability of mitotic figures due to prefixation and fixation
      issues and problems with interobserver reproducibility of counts. This paper
      reviews factors that affect the identification of mitotic figures and the
      determination of mitosis counts. The role mitosis evaluation plays in the
      evaluation of certain neoplasms of the central nervous system is discussed.

PMID- 12071634
TI  - Cytoarchitectural abnormalities in hippocampal sclerosis.
AB  - Hippocampal sclerosis (HS) is the most common pathological substrate for temporal
      lobe epilepsy with a characteristic pattern of loss of principle neurons
      primarily in CA1 and hilar subfields. Other cytoarchitectural abnormalities have
      been identified in human HS specimens, including dispersion of dentate granule
      cells and cytoskeletal abnormalities in residual hilar cells. The incidence of
      these features, their relationship to the severity of HS and potential indication
      of underlying hippocampal maldevelopment is unverified. In a series of 183
      hippocampectomies we identified classical HS (grades 3 and 4) in 90% of
      specimens, granule cell disorganization or severe dispersion in 40% of cases with
      a bilaminar pattern in 10%, and cytoskeletal abnormalities in hilar cells in 55%
      of cases. The severity of granule cell disorganization correlated closely with
      the degree of hippocampal neuronal loss but not with the age at first seizure or
      a history of a precipitating event for epilepsy such as prolonged febrile
      seizures. These findings suggest that granule cell disorganization is closely
      linked with the progression of HS rather than a hallmark of impaired hippocampal
      maturation. Furthermore, stereological quantitation of granule cells showed
      evidence of cell loss but greater numbers in regions of maximal dispersion, which
      may indicate enhanced neurogenesis of these cells. Quantitation of reelin-and
      calretinin-positive Cajal-Retzius cells in the dentate gyrus molecular layer in
      26 cases showed no correlation between the number of these cells and the severity
      of granule cell dispersion, but increased numbers of these cells were present in
      HS with respect to control groups. Although a role for Cajal-Retzius cells is
      therefore not implicated in the mechanism of granule cell disorganization, their
      excess number may be indicative of underlying hippocampal maldevelopment in HS.

PMID- 12071636
TI  - Hypomethylated X chromosome gain and rare isochromosome 12p in diverse
      intracranial germ cell tumors.
AB  - Twenty-five primary intracranial germ cell tumors (11 germinomas, 5 teratomas, 5
      mixed teratomas-germinomas. 1 mixed choriocarcinoma-teratoma, 1 yolk sac tumor, 1
      mixed yolk sac tumor-teratoma, and 1embryonal carcinoma; from 24 males and 1
      female) were studied by fluorescence in situ hybridization with probes to the X
      and Y chromosomes, chromosome 12p, the CDKN2A/p16 gene, and chromosome 13q-loci
      previously noted to be altered in either intracranial or systemic germ cell
      tumors. An increased number of X chromosomes, typically 1 extra copy, was
      observed in 23 of 25 cases (92%), with methylation-sensitive PCR demonstrating
      that the additional X chromosomes were hypomethylated in 13 of 16 (81%) studied
      tumors. Five cases (20%) had increased copy numbers of 12p (including tumors with
      isochromosome 12p), and 3 (12%) had 13q loss. No tumors had CDKN2A/p16 deletion
      or mutation, and 16 of 25 (64%) were positive for p16 expression by
      immunohistochemistry. Genetic alterations such as isochromosome 12p, 13q loss and
      CDKN2A/p16 are therefore not common in intracranial germ cell tumors. However,
      gains of hypomethylated, active X chromosomes occur in nearly all intracranial
      germ cell tumors, regardless of histological subtype. Along with the observed
      male predominance of intracranial germ cell tumors and the predisposition in
      Klinefelter syndrome patients for these lesions, the data argue strongly that sex
      chromosome aberrations, rather than isochromosome 12p, are integral to
      intracranial germ cell tumorigenesis

PMID- 12071635
TI  - Disorganization of the desmin cytoskeleton and mitochondrial dysfunction in
      plectin-related epidermolysis bullosa simplex with muscular dystrophy.
AB  - Mutations of the human plectin gene (Plec1) cause autosomal recessive
      epidermolysis bullosa simplex with muscular dystrophy (EBS-MD). Here, we report
      on molecular mechanisms leading to severe dystrophic muscle alterations in EBS
      MD. Analysis of a 25-yr-old EBS-MD patient carrying a novel homozygous 16-bp
      insertion mutation (13803ins16/13803ins16) close to the intermediate filament
      (IF) binding site of plectin showed severe disorganization of the myogenic IF
      cytoskeleton. Intermyofibrillar and subsarcolemmal accumulations of assembled but
      highly unordered desmin filaments may be attributed to impaired desmin binding
      capability of the mutant plectin. This IF pathology was also associated with
      severe mitochondrial dysfunction, suggesting that the muscle pathology of EBS-MD
      caused by IF disorganization leads not only to defects in mechanical force
      transduction but also to metabolic dysfunction. Beyond EBS-MD, our data may
      contribute to the understanding of other myopathies characterized by sarcoplasmic
      IF accumulations such as desminopathies or alpha-B-crystallinopathies.

PMID- 12071637
TI  - VCAM-1-positive microglia target oligodendrocytes at the border of multiple
      sclerosis lesions.
AB  - The distribution and lineage of vascular cell adhesion molecule-1 (VCAM-1)
      positive cells was investigated in 43 lesions from the brain tissue of patients
      with multiple sclerosis (MS). Numerous VCAM-1-positive macrophages/microglia were
      detected at the edges of MS lesions. Quantitative analysis of 6 active, 7 chronic
      active, and 4 chronic inactive MS lesions identified most VCAM-1-positive cells
      at the actively demyelinating borders of active (102/mm3) and chronic active
      (29/mm3) lesions, but rarely in chronic inactive lesions (4/mm3). Further,
      approximately 17% of the VCAM-1-positive cells closely apposed or surrounded
      oligodendrocyte perikarya at the edges of active and chronic active lesions that
      were sites of ongoing demyelination. Endothelial cells were VCAM-1-negative in
      both lesion and non-lesion MS brain tissue. This report is the first to document
      direct microglial interaction with oligodendrocytes in MS.

PMID- 12071638
TI  - Argyrophilic grain disease is a sporadic 4-repeat tauopathy.
AB  - Argyrophilic grain disease (AGD) was first reported as an adult-onset dementia,
      but recent studies have emphasized personality change, emotional imbalance, and
      memory problems as clinical features of AGD. AGD is characterized by spindle- or
      comma-shaped argyrophilic grains in the neuropil of entorhinal cortex,
      hippocampus, and amygdala. Immunohistochemistry with monoclonal antibodies
      specific to tau isoforms with four (4R) or three (3R) repeats in the microtubule
      binding domain showed immunostaining of grains with 4R, but not 3R, tau
      antibodies, suggesting that AGD was a 4R tauopathy. The tau isoform composition
      of AGD was confirmed with densitometric analysis of Western blots of sarkosyl
      insoluble tau from the medial temporal lobe of AGD brains with a range of
      concurrent neurofibrillary pathology and compared with Alzheimer controls. The
      4R/3R ratio was 1 or less for Alzheimer disease; the 4R/3R ratio was more than 1
      for AGD, decreasing with increasing neurofibrillary pathology and demonstrating
      that insoluble tau in AGD was enriched in 4R tau. The frequency of the extended
      tau haplotype was not different in AGD compared to other sporadic 4R tauopathies,
      progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD).
      Furthermore, AGD occurred in PSP and CBD more frequently than in dementia
      controls, including Alzheimer disease. These results suggest that AGD, PSP and
      CBD are 4R tauopathies that share common pathologic, biochemical, and genetic
      characteristics.

PMID- 12071639
TI  - Colocalization and fluorescence resonance energy transfer between cdk5 and AT8
      suggests a close association in pre-neurofibrillary tangles and neurofibrillary
      tangles.
AB  - Cyclin-dependent kinase 5 (cdk5) is a serine/threonine kinase that, when
      activated, induces neurite outgrowth. Recent in vitro studies have shown that
      cdk5 phosphorylates tau at serine 199, serine 202, and threonine 205 and that
      p25, an activator of cdk5, is increased in Alzheimer disease (AD). Since tau is
      hyperphosphorylated at these sites in neurofibrillary tangles, we examined brain
      tissue from patients with AD and normal elderly control cases to determine
      whether cdk5 and these phosphoepitopes colocalize in neurofibrillary tangles.
      Adjacent temporal lobe sections were double immunostained with a polyclonal anti
      cdk5 and monoclonal AT8 (which recognizes phosphorylated serine 199, serine 202,
      and threonine 205 in tau) antibodies. A subset of AT8 phosphotau-positive neurons
      was immunoreactive for cdk5 in entorhinal (area 28) and perirhinal (area 35)
      cortices and CA1 of the hippocampus. We assessed the ratio of cdk5-positive cells
      to AT8-positive cells and found that there is a higher degree of colocalization
      in pre-neurofibrillary tangles as opposed to intraneuronal and extraneuronal
      neurofibrillary tangles. We further examined colocalization using fluorescence
      resonance energy transfer. This suggests a close, stable intermolecular
      association between cdk5 and phosphorylated tau, consistent with phosphorylation
      of tau by cdk5 in AD brain.

PMID- 12071640
TI  - Neuromuscular pathology in hereditary gelsolin amyloidosis.
AB  - Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder
      reported worldwide in kindreds with a G654A or G654T gelsolin gene mutation. The
      clinically characteristic peripheral nerve involvement has been poorly
      characterized morphologically, and its pathogenesis remains unknown. We studied
      peripheral nerve and skeletal muscle biopsy or autopsy specimens of 35 patients
      with a G654A gelsolin gene mutation. Histological, immunohistochemical, and
      electron microscopic studies showed consistent deposition of gelsolin amyloid
      (AGel), particularly in the vascular walls and perineurial sheaths. Nerve roots
      were more severely affected than distal nerves. The amyloid deposits also
      displayed variable immunoreactivity for apolipoprotein E, amyloid P component,
      cystatin C, and alpha-smooth muscle actin. Sural nerve morphometry showed
      preferential age-related large myelinated nerve fiber loss and reduction of
      myelin sheath cross-sectional area. There was evidence of denervation atrophy and
      fiber type grouping in skeletal muscle. Our study shows that marked proximal
      nerve involvement with AGel angiopathy is an essential feature of AGel
      amyloidosis. The preferential large fiber loss, not generally seen in amyloid
      neuropathy, may be caused by ischemia due to AGel angiopathy. Deficient actin
      modulation by variant gelsolin in neurons and Schwann cells, however, may alter
      axonal transport and myelination and contribute to AGel polyneuropathy.

PMID- 12071641
TI  - Purification and characterization of the common yolk protein, vitellin, from the
      estuarine amphipod Leptocheirus plumulosus.
AB  - Vitellin is a major yolk protein that plays a significant role in the embryonic
      development of crustacean embryos. This protein was rapidly purified from embryos
      of the estuarine amphipod, Leptocheirus plumulosus, by subjecting the crude
      protein homogenate to high affinity column chromatography. SDS-PAGE revealed a
      single band with an approximate molecular weight of 200,000 daltons. Vitellin was
      characterized by SDS-PAGE techniques and amino acid composition analysis. L.
      plumulosus vitellin is a lipoglycophosphoprotein with serine, glutamic
      acid/glutamine, alanine, and aspartic acid/asparagine accounting for almost 66%
      of all amino acid residues. Polyclonal antibodies were raised against L.
      plumulosus vitellin and antibody reactivity was verified by dot-blotting and
      immuno-fluorescence confocal microscopy. These antibodies are specific for
      purified vitellin and show little cross-reactivity with other embryonic proteins.

PMID- 12071642
TI  - Synthesis and immunological effect of thymic humoral factor-gamma-2 analogues.
AB  - Nine analogues of thymic humoral factor (THF)-gamma-2 were prepared by the solid
      phase method, and their in vitro restoring effect on the impaired blastogenic
      response of phytohemagglutinin(PHA)-stimulated T-lymphocytes of uremic patients
      with infectious diseases were examined. The results were as follows: [Arg6]-THF
      gamma-2 exhibited higher restoring activity than that of our synthetic THF-gamma
      2. [Sar4]-, [Val1]-, [Arg3]-, [Gly5]-, and [Asn3]-THF-gamma-2 were also active
      but less potent than that of our synthetic THF-gamma-2. Three other peptides,
      [beta-Ala4]-, [Arg2]-, and [Gln2]-THF-gamma-2, did not show any restoring
      activity on the impaired blastogenic response of uremic patients with infectious
      disease.

PMID- 12071643
TI  - An enzymatic method for removal of phenol from industrial effluent.
AB  - Phenols in an aqueous solution were removed after treatment with peroxidase in
      the presence of hydrogen peroxide. Phenols occur in wastewater of a number of
      industries, such as high temperature coal conversion, petroleum refining, resin
      and plastic, wood and dye industries, etc. It can be toxic when present at
      elevated levels and is known to be carcinogeneous. Thus, removal of such compound
      from these industrial effluents is of great importance. An enzymatic method for
      removal of phenols from industrial wastewater, using turnip peroxidase, has been
      developed. Phenol-containing industrial wastewater was treated with immobilized
      turnip peroxidase in the presence of hydrogen peroxide. In the reaction, a number
      of phenols are oxidized to form the corresponding free radicals in the presence
      of hydrogen peroxide as an oxidant. Free radicals polymerize to form substances
      that are less soluble in water than the original substances. The precipitates
      were removed by conventional methods and residual phenol was estimated. The
      present report describes the immobilization of turnip peroxidase on silica via
      covalent coupling, and its utility in phenol removal. A comparative study was
      also carried out with other immobilization techniques, viz., calcium alginate
      entrapment, polyacrylamide gel entrapment, etc. Peroxidase, covalently bound to
      silica, showed 95% removal of phenol, whereas naphthol was removed up to 99%.

PMID- 12071644
TI  - Bienzymatic amperometric sensor for protein assay in milk.
AB  - A new bienzymatic amperometric sensor is proposed for the assay of the protein
      content of milk. The sensor is based on two enzymes: carboxypeptidase A and L
      amino acid oxidase. The response characteristics obtained for this sensor
      (detection limit of 1.5 micromol/L, linear concentration range between 1.8 and
      2.8 micromol/L), as well as high selectivity over possible interferences from
      milk, made it applicable as a detector in flow injection analysis (FIA). The
      response characteristics obtained in the non-equilibrium conditions (FIA system)
      are: detection limit of 1.5 micromol/L and linear concentration range between 2
      and 3.5 micromol/L. Without FIA, the average recovery of proteins from milk and
      milk products is 99.06 +/- 0.07% and, by utilization of FIA, it increased to
      99.73 +/- 0.03. The sensor proved a good reliability for the assay of proteins in
      milk and milk products.

PMID- 12071645
TI  - Purification of lactoperoxidase from creek-water buffalo milk and investigation
      of kinetic and antibacterial properties.
AB  - Water buffalo lactoperoxidase (WBLP) was purified with Amberlite CG 50 H+ resin,
      CM Sephadex C-50 ion-exchange chromatography, and Sephadex G-100 gel filtration
      chromatography from skim milk. All purification steps of the WBLP were shown with
      SDS-PAGE and Rz (A412/A280) controlled the purification degree of the enzyme. Rz
      value for the purified WBLP was 0.8. To determine purification steps and kinetic
      properties, the activity of enzyme was measured by using 2,2-azino-bis-(3
      ethylbenzthiazoline-6 sulfonic acid) diammonium salt (ABTS) as a choromogenic
      substrate at pH=6. Km, Vmax, optimum pH, and optimum temperature for the WBLP
      were found by means of graphics for ABTS as substrates. Optimum pH and optimum
      temperature of the WBLP were 6 and 60 degrees C, respectively. Km value at
      optimum pH and optimum temperature for the WBLP was 0.82 mM. Vmax value at
      optimum pH and optimum temperature was 13.7 micromol/mL x min. Km value at
      optimum pH and 25 degrees C for the WBLP was 0.77 mM. Vmax value at optimum pH
      and 25 degrees C was 4.83 micromol/mL x min. The purified WBLP was found to have
      high antibacterial activity in a thiocynate-H2O2 medium for some pathogenic
      bacteria, such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeruginose, Shigella sonnei, Staphylococcus saphrophyticus, Staphylococcus
      epidermidis, and Shigella dysenteriae and compared with well known antibacterial
      substances such as tetracycline, penicillin, and netilmicine.

PMID- 12071646
TI  - dUTPase from Escherichia coli; high-level expression and one-step purification.
AB  - The dut gene, which encodes Escherichia coli deoxyuridine 5'-triphosphate
      nucleotidohydrolase (dUTPase), has been recloned to increase overexpression of
      the enzyme and to enable simplification of the purification protocol into a one
      step procedure. The gene was cloned into the vector pET-3a and expressed in E.
      coli BL21(DE3) pLysS under the control of a bacteriophage T7 promotor. Induction
      results in production of dUTPase corresponding to 60% of the extracted protein.
      Phosphocellulose chromatography at low pH was utilised for one-step purification,
      resulting in a homogenous preparation of the recombinant protein with a highly
      specific activity. The yield of purified enzyme is 500 mg per litre of bacterial
      culture, a significant increase compared to previously employed methods.

PMID- 12071647
TI  - Purification and investigation of some kinetic properties of glucose-6-phosphate
      dehydrogenase from parsley (Petroselinum hortense) leaves.
AB  - In this study, glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+
      oxidoreductase, EC 1.1.1.49; G6PD) was purified from parsley (Petroselinum
      hortense) leaves, and analysis of the kinetic behavior and some properties of the
      enzyme were investigated. The purification consisted of three steps: preparation
      of homogenate, ammonium sulfate fractionation, and DEAE-Sephadex A50 ion exchange
      chromatography. The enzyme was obtained with a yield of 8.79% and had a specific
      activity of 2.146 U (mg protein)(-1). The overall purification was about 58-fold.
      Temperature of +4 degrees C was maintained during the purification process.
      Enzyme activity was spectrophotometrically measured according to the Beutler
      method, at 340 nm. In order to control the purification of enzyme, SDS
      polyacrylamide gel electrophoresis was carried out in 4% and 10% acrylamide for
      stacking and running gel, respectively. SDS-polyacrylamide gel electrophoresis
      showed a single band for enzyme. The molecular weight was found to be 77.6 kDa by
      Sephadex G-150 gel filtration chromatography. A protein band corresponding to a
      molecular weight of 79.3 kDa was obtained on SDS-polyacrylamide gel
      electrophoresis. For the enzymes, the stable pH, optimum pH, and optimum
      temperature were found to be 6.0, 8.0, and 60 degrees C, respectively. Moreover,
      KM and Vmax values for NADP+ and G6-P at optimum pH and 25 degrees C were
      determined by means of Lineweaver-Burk graphs. Additionally, effects of
      streptomycin sulfate and tetracycline antibiotics were investigated for the
      enzyme activity of glucose-6-phosphate dehydrogenase in vitro.

PMID- 12071649
TI  - Classification of environmental pollutants for global mobility potential.
AB  - The environmental behaviour of global organic contaminants is known to be
      controlled by the physico-chemical properties of the compounds themselves. The
      principal component analysis of some physico-chemical properties, particularly
      relevant in determining mobility potential (vapour pressure, Henry's law
      constant, water solubility, K(OW), K(OA) and melting point) allows a multivariate
      approach to a ranking of organic pollutants according to their intrinsic tendency
      towards mobility, and the definition of four a priori mobility classes for
      screening purposes. Quantitative structure-property relationships (QSPRs) were
      used to predict missing values for octanol/air partition coefficients. Finally, a
      classification method employing theoretical molecular descriptors was used to
      assign studied chemicals to four mobility classes. The proposed approach
      assesses, directly and simply, a pollutant's inherent tendency towards mobility
      using only knowledge of the pollutant's molecular structure; the approach is
      particularly useful for a preliminary screening and the prioritisation of organic
      pollutants of emerging environmental concern.

PMID- 12071648
TI  - Co-overexpression of folding modulators improves the solubility of the
      recombinant guinea pig liver transglutaminase expressed in Escherichia coli.
AB  - Transglutaminases (EC 2.3.2.13) catalyze the formation of epsilon-(gamma
      glutamyl)lysine cross-links and the substitution of primary amines for the gamma
      carboxamide groups of protein bound glutamine residues, and are involved in many
      biological phenomena. Transglutaminase reactions are also applicable in applied
      enzymology. Here, we established an expression system of recombinant mammalian
      tissue-type transglutaminase with high productivity. Overexpression of guinea pig
      liver transglutaminase in Escherichia coli, using a plasmid pET21-d, mostly
      resulted in the accumulation of insoluble and inactive enzyme protein. By the
      expression culture at lower temperatures (25 and 18 degrees C), however, a
      fraction of the soluble and active enzyme protein slightly increased. Co
      overexpression of a molecular chaperone system (DnaK-DnaJ-GrpE) and/or a folding
      catalyst (trigger factor) improved the solubility of the recombinant enzyme
      produced in E. coli cells. The specific activity, the affinity to the amine
      substrate, and the sensitivity to the calcium activation and GTP inhibition of
      the purified soluble recombinant enzyme were lower than those of the natural
      liver enzyme. These results indicated that co-overexpression of folding
      modulators tested improved the solubility of the overproduced recombinant
      mammalian tissue-type transglutaminase, but the catalytic properties of the
      soluble recombinant enzyme were not exactly the same as those of the natural
      enzyme.

PMID- 12071650
TI  - Steric and electrostatic effects in dye-cellulose interactions by the MTD and
      CoMFA approaches.
AB  - This paper presents the application of the MTD (minimal steric difference)
      analysis and CoMFA (comparative molecular field analysis) to series of
      anthraquinone vat, mono and disazo and disperses dyes with known affinities for
      cellulose fiber. A comparison of the results demonstrates that these methods
      usually agree with the prediction of structural features favorable for dyeing. A
      series of n = 49 anthraquinone vat dyes was studied by MTD with r2 between 0.903
      and 0.941 and r2CV values in the range of 0.827-0.878. For CoMFA, r2 = 0.992,
      r2CV = 0.841 were obtained; the CoMFA field is in rather good agreement with
      vertex attributions, by MTD for attractive and repulsive vertices. Anionic disazo
      dyes were studied by the CoMFA method (n = 21, r2 = 0.999, r2CV = 0.703). Monoazo
      dyes (several series) were studied by CoMFA and MTD. The effect of lipophilicity
      on dye fiber affinity was, also, studied for these dyes. Disperse dye adsorption
      was analyzed by MTD and CoMFA (n = 27, r2 = 0.925, r2CV = 0.776). Conclusions
      refer to the effect of structural features of dye molecules upon adsorption on
      cellulose fibers.

PMID- 12071651
TI  - Adenosine A2A receptor agonists: CoMFA-based selection of the most predictive
      conformation.
AB  - A step-wise comparative molecular field analysis (CoMFA)-based procedure was
      applied to a series of 51 2-oxyadenosines in order to select the most predictive
      conformation for binding to A2A adenosine receptor (AR). The highest correlation
      and predictive power were found for conformers with side chain at 2nd position
      oriented in the direction opposite to the exocyclic amino group on the adenine
      ring (torsion N1C2OR = 120 degrees) and fully extended. The interaction of ligand
      and receptor is under steric and electrostatic control. The steric contribution
      is of a greater importance for the predictivity than the electrostatic one.
      Hydrophobicity of the compounds investigated does not affect significantly either
      the affinity to A2A AR, nor the predictivity of the models.

PMID- 12071652
TI  - A theoretical study of model lipid monolayers.
AB  - Studies of pure phospholipid monolayers or various well defined lipid mixtures
      have greatly contributed to the current knowledge of the relationship between
      monolayer composition and its properties and to understand how their
      physicochemical properties, e.g. refraction, polarization, are controlled by
      structural variations at the molecular level. Therefore, an attempt was made to
      investigate model lipid molecules adsorbed on the air/water interface. Semi
      empirical (AM1) quantum chemical calculations were performed for several clusters
      and were compared with experimental data. The optimized acidic molecules show a
      marked tendency to group forming domains. An increase in the number of surfactant
      molecules in the cluster leads to a decrease in the effective headgroup area. On
      the other hand, the area grows with the increase of the degree of ionization.
      Both relations are in accordance with the experimental trends and the
      electrostatic theory. The employed theoretical approach proves to be applicable
      to the study of monolayers, thus providing a reliable description at molecular
      level of the traditionally phenomenological investigations in the field.

PMID- 12071653
TI  - Theoretical study of fast repair of DNA damage by cistanoside C and analogs:
      mechanism and docking.
AB  - Experiments show that the natural substances phenylpropanoid glycosides (PPGs)
      extracted from pelicularis spicata are capable of repairing DNA damaged by oxygen
      radicals. Based on kinetic measurements and experiments on tumor cells, a
      theoretical study of the interaction between PPG molecules and isolated DNA
      bases, as well as a DNA fragment has been performed. An interaction mechanism
      reported early has been refined. The docking calculations performed using
      junction minimization of nucleic acids (JUMNA) software showed that the PPG
      molecules can be docked into the minor groove of DNA and form complexes with the
      geometry suitable for an electron transfer between guanine radical and the
      ligand. Such complexes can be formed without major distortions of DNA structure
      and are further stabilized by the interaction with the rhamnosyl side-groups.

PMID- 12071654
TI  - Prediction of acute toxicity of chemicals in mixtures: worms Tubifex tubifex and
      gas/liquid distribution.
AB  - The aim of this contribution is to support our proposal of the procedure for
      predicting acute toxicity of binary mixtures by QSAR analysis techniques. The
      changes of a mixture composition are described by molar ratio R and visualized in
      the R-plot (QCAR--quantitative composition-activity relationships). The approach
      was inspired by Rault and Dalton's laws, their positive and negative deviations
      in the behavior of a mixture of real gases, by Loewe and Muischnek isoboles and
      by the Finney test of additivity. Acute toxicity was determined by the laboratory
      test with woms Tubifex tubifex. The additivity of the acute toxicity in the
      binary mixture benzene + nitrobenzene was confirmed and a new interaction is
      described: "mixed interaction" with the binary mixture aniline + ethanol. The
      "mixed interaction" means that depending on mixture composition, both
      potentiation and inhibition can occur. As the first physicochemical descriptor of
      the changes caused by the changing composition of binary mixtures, the gas/liquid
      equilibrium was studied and a composition of the gaseous phase was determined by
      a gas chromatographic method. The method for determination of concentrations in
      the gaseous phase was described. The gaseous phase composition of benzene +
      nitrobenzene. benzene + ethanol, benzene + aniline and ethanol + aniline mixtures
      was analyzed. It was found that if the concentrations of the mixture's components
      in the gaseous phase behave nonideally (they are not additive), the acute
      toxicity of the same mixture is not additive as well. Another descriptor to
      distinguish between potentiation and inhibition will be, however, necessary. The
      properties, both gaseous phase composition and the acute toxicity, of the benzene
      + nitrobenzene mixture are additive. In mixtures with the mixed interaction, the
      R-plot of the composition of the gaseous phase is complex with a large variation
      of results.

PMID- 12071655
TI  - Dissolved organic carbon--contaminant interaction descriptors found by 3D force
      field calculations.
AB  - Enthalpies of transfer at 300 K of various partitioning processes were calculated
      in order to study the suitability of 3D force fields for the calculation of
      partitioning constants. A 3D fulvic acid (FA) model of dissolved organic carbon
      (DOC) was built in a MM+ force field using AMI atomic charges and geometrical
      optimization (GO). 3,5-Dichlorobiphenyl (PCB14), 4,4'-dichlorobiphenyl (PCB15),
      1,1,1-trichloro-2,2-bis-(4-chlorophenyl)-ethane (PPDDT) and 2-chloro-4-ethylamino
      6-isopropylamino-s-triazine (Atrazine) were inserted into different sites and
      their interaction energies with FA were calculated. Energies of hydration were
      calculated and subtracted from FA-contaminant interactions of selected sites. The
      resulting values for the enthalpies of transfer from water to DOC were 2.8, -1.4,
      -6.4 and 0.0 kcal/mol for PCB 14, PCB15, PPDDT and Atrazine, respectively. The
      value of PPDDT compared favorably with the experimental value of -5.0 kcal/mol.
      Prior to this, the method was studied by the calculation of the enthalpies of
      vaporization and aqueous solution using various force fields. In the MM + force
      field GO predicted enthalpies of vaporization deviated by +0.7 (PCB14), +3.6
      (PCB15) and -0.7 (PPDDT)kcal/mol from experimental data, whereas enthalpies of
      aqueous solution deviated by -3.6 (PCB14), +5.8 (PCB15) and +3.7 (PPDDT)
      kcal/mol. Only for PCB14 the wrong sign of this enthalpy value was predicted.
      Potential advantages and limitations of the approach were discussed.

PMID- 12071656
TI  - Structure-water solubility modeling of aliphatic alcohols using the weighted path
      numbers.
AB  - The structure-water solubility modeling of aliphatic alcohols was performed using
      the weighted path numbers. Aliphatic alcohols were represented by weighted trees.
      The weight of the edge representing C-O bond was taken to be x, while the weights
      of C-C bonds were taken to be all equal to one. Four (one-, two-, three- and four
      descriptor) models with weighted path numbers were considered. They were compared
      with models based on surface areas of aliphatic alcohols, models based on the
      vertex-connectivity indices for the corresponding alkanes, models based on
      orthogonal valence vertex-connectivity indices, models based on valence vertex-
      and edge-connectivity indices with optimum exponents and models based on weighted
      line graphs. The main result of this comparative study is that the models based
      on two, three, or four weighted path numbers posses the best statistical
      characteristics of all models considered in this paper. In addition, the
      predictive performance of these models was also tested using the training/test
      set partition. Very good and stable predictions for 19 test set compounds were
      obtained. For this data set we find, in all performed tests of models, that
      optimum x values are in the range 3.0-4.0. This result supports views about the
      potential of the weighted path numbers for deriving high quality structure
      property models.

PMID- 12071657
TI  - A new scheme for electronegativity equalization as a source of electronic
      descriptors: application to chemical reactivity.
AB  - Recently, we have proposed a new unconventional scheme of electronegativity
      equalization. We assume that atomic electronegativities are equalized in a
      molecule in the same manner as electrical potentials in the nodes of a closed
      electrical network, with the molecule being represented by a molecular graph
      (MG). Computational procedure includes several operations over the matrices
      associated with MG. The only parameter used is the atomic electronegativity (EN).
      The method is very fast and easy-to-implement. With the help of the method one
      can generate a family of electronic descriptors (equalized or "effective" ENs and
      atomic charges) which are applicable to the treatment of some types of chemical
      reactivity. Quite good correlations of the descriptors obtained are observed for
      such thermodynamic and kinetic data as proton affinity and Taft's inductive
      sigma* constants. The EN equalization scheme suggested can be used as an
      independent tool for molecular electrostatics modeling, or can be implemented
      into an integrated QSAR software.

PMID- 12071658
TI  - Probabilistic assessment of biodegradability based on metabolic pathways: catabol
      system.
AB  - A novel mechanistic modeling approach has been developed that assesses chemical
      biodegradability in a quantitative manner. It is an expert system predicting
      biotransformation pathway working together with a probabilistic model that
      calculates probabilities of the individual transformations. The expert system
      contains a library of hierarchically ordered individual transformations and
      matching substructure engine. The hierarchy in the expert system was set
      according to the descending order of the individual transformation probabilities.
      The integrated principal catabolic steps are derived from set of metabolic
      pathways predicted for each chemical from the training set and encompass more
      than one real biodegradation step to improve the speed of predictions. In the
      current work, we modeled O2 yield during OECD 302 C (MITI I) test. MITI-I
      database of 532 chemicals was used as a training set. To make biodegradability
      predictions, the model only needs structure of a chemical. The output is given as
      percentage of theoretical biological oxygen demand (BOD). The model allows for
      identifying potentially persistent catabolic intermediates and their molar
      amounts. The data in the training set agreed well with the calculated BODs (r2 =
      0.90) in the entire range i.e. a good fit was observed for readily, intermediate
      and difficult to degrade chemicals. After introducing 60% ThOD as a cut off value
      the model predicted correctly 98% ready biodegradable structures and 96% not
      ready biodegradable structures. Crossvalidation by four times leaving 25% of data
      resulted in Q2 = 0.88 between observed and predicted values. Presented approach
      and obtained results were used to develop computer software for biodegradability
      prediction CATABOL.

PMID- 12071659
TI  - The effect of precision of molecular orbital descriptors on toxicity modeling of
      selected pyridines.
AB  - The response-surface approach to QSARs attempts to model toxic potency of diverse
      groups of chemicals while avoiding problems associated with the identification of
      the mechanism of toxic action or specific chemical class often associated with
      other approaches. However, while hydrophobicity-dependent, simple regression
      QSARs derived for congeneric series of organic compounds typically have
      coefficients of determination greater than 0.90, more heterogeneous multiple
      regression QSARs exhibit typically 10-15% more unexplained variability. One
      difference between these approaches is the use of a quantum chemical (QC)
      descriptor, particularly molecular orbital (MO) energy values such as the energy
      of the lowest unoccupied molecular orbital (E(LUMO)). The reduced statistical fit
      exhibited by QSAR models, which include these QC-MO descriptors, could be a
      result of the variability inherent in the calculation of these descriptors. The
      present investigation with a structurally and mechanistically diverse set of
      pyridines revealed that variability is associated with the calculation of the MO
      descriptor E(LUMO) both between selected Hamiltonians and selected software
      packages. However, this variability in no way affects the statistical
      significance of QSARs for toxicity using these values. Specifically, the E(LUMO)
      values calculated with the PM3 and AM1 Hamiltonians in the two software packages
      were highly related. There was no relationship between molecular complexity or
      chemical reactivity and increased differences in individual ELUMO values as
      described by the standard errors of the mean. Although nine appeared to be the
      number of calculations, which best minimizes the standard error in energy values
      relative to computational costs; this minimization did not alter the statistics
      of the QSARs derived with single vs. mean E(LUMO) values. While the energy of the
      highest occupied molecular orbital (E(HOMO)) values were not used in the modeling
      of toxicity, a comparison of these values revealed greater variability between
      the Hamiltonians and software packages than observed for ELUMO values.
      Examination of the magnitudes of standard error of the E(HOMO) values in
      connection to structural features or reactivity likewise revealed no trends.

PMID- 12071660
TI  - Charged partial surface area (CPSA) descriptors QSAR applications.
AB  - The charged partial surface area, or CPSA descriptors were originally designed
      for use in structure-physical relationship studies to capture information about
      the features of molecules responsible for polar intermolecular interactions.
      Since their development, they have found applications in a broad variety of both
      structure-property and structure-activity relationship studies. In the present
      work, the CPSA descriptors are examined in more detail, evaluating their
      characteristics with regard to conformational dependence, sources of partial
      atomic charges, utility of whole molecule and substructure varieties, and the
      inclusion or exclusion of explicit hydrogens. Additionally, an examination of the
      physical interpretation that can be derived from structure-activity relationships
      that incorporate the CPSA descriptors is made. Most recently, the CPSA
      descriptors have been found to be practically useful in the study of acute
      aquatic toxicity where they appear to provide an alternative to LUMO energy level
      measures for describing global and local electrophilicity in cases of non
      covalent molecular interactions. A second example illustrates the ability of the
      CPSA descriptors to discriminate agonists and antagonists among compounds that
      bind strongly at the estrogen receptor. While measures of global and local
      nucleophilicity and interatomic distances are required to explain receptor
      binding, volumetric parameters, such as CPSAs, were found to be necessary to
      provide separation between reactivity patterns for agonists and antagonists, all
      having high binding affinity to estrogen receptor.

PMID- 12071661
TI  - A reactivity pattern for discrimination of ER agonism and antagonism based on 3-D
      molecular attributes.
AB  - Various models have been developed to predict the relative binding affinity (RBA)
      of chemicals to estrogen receptors (ER). These models can be used to prioritize
      chemicals for further tiered biological testing to assess the potential for
      endocrine disruption. One shortcoming of models predicting RBA has been the
      inability to distinguish potential receptor antagonism from agonism, and hence in
      vivo response. It has been suggested that steroid receptor antagonists are less
      compact than agonists; thus, ER binding of antagonists may prohibit proper
      alignment of receptor protein helices preventing subsequent transactivation. The
      current study tests the theory of chemical bulk as a defining parameter of
      antagonism by employing a 3-D structural approach for development of reactivity
      patterns for ER antagonists and agonists. Using a dataset of 23 potent ER ligands
      (16 agonists, 7 antagonists), molecular parameters previously found to be
      associated with ER binding affinity, namely global (E(HOMO)) and local (donor
      delocalizabilities and charges) electron donating ability of electronegative
      sites and steric distances between those sites, were found insufficient to
      discriminate ER antagonists from agonists. However, parameters related to
      molecular bulk, including solvent accessible surface and negatively charged Van
      der Waal's surface, provided reactivity patterns that were 100% successful in
      discriminating antagonists from agonists in the limited data set tested. The
      model also shows potential to discriminate pure antagonists from partial
      agonist/antagonist structures. Using this exploratory model it is possible to
      predict additional chemicals for their ability to bind but inactivate the ER,
      providing a further tool for hypothesis testing to elucidate chemical structural
      characteristics associated with estrogenicity and anti-estrogenicity.

PMID- 12071662
TI  - Reactivity profiles of ligands of mammalian retinoic acid receptors: a
      preliminary COREPA analysis.
AB  - Retinoic acid and associated derivatives comprise a class of endogenous hormones
      that bind to and activate different families of retinoic acid receptors (RARs,
      RXRs), and control many aspects of vertebrate development. Identification of
      potential RAR and RXR ligands is of interest both from a pharmaceutical and
      toxicological perspective. The recently developed COREPA (COmmon REactivity
      PAttern) algorithm was used to establish reactivity profiles for a limited data
      set of retinoid receptor ligands in terms of activation of three RARs (alpha,
      beta, gamma) and an RXR (alpha). Conformational analysis of a training set of
      retinoids and related analogues in terms of thermodynamic stability of conformers
      and rotational barriers showed that these chemicals tend to be quite flexible.
      This flexibility, and the observation that relatively small energy differences
      between conformers can result in significant variations in electronic structure,
      highlighted the necessity of considering all energetically reasonable conformers
      in defining common reactivity profiles. The derived reactivity patterns for three
      different subclasses of the RAR (alpha, beta, gamma) were similar in terms of
      their global electrophilicity (nucleophilicity) and steric parameters. However,
      the profile of active chemicals with respect to interaction with the RXR-alpha
      differed qualitatively from that of the RARs. Variations in reactivity profiles
      for the RAR versus RXR families would be consistent with established differences
      in their affinity for endogenous retinoids, likely reflecting functional
      differences in the receptors.

PMID- 12071664
TI  - Fischer 344 and wistar rats differ in anxiety and habituation but not in water
      maze performance.
AB  - The fact that various neuropharmacological substances have anxiolytic as well as
      amnesic effects suggests that neuronal mechanisms of anxiety and learning/memory
      closely interact. Hence, we hypothesized that differences in anxiety-related
      behavior could be accompanied with differences in cognition or habituation. Two
      rat strains with different levels of anxiety, more anxious Fischer 344 rats by
      Charles River (FC) and less anxious Wistar rats by Winkelmann (WW), were tested
      in the Morris water maze task and an open field test for habituation learning.
      Additionally, we investigated the effect of different light intensities on the
      performance in the Morris water maze and the elevated plus maze. The results of
      the water maze task indicate that differences in anxiety-related behavior do not
      go along with differences in this performance of learning/memory. Moreover, the
      test was not affected by different light intensities. In contrast, illumination
      did affect performance in the elevated plus maze test, wherein dim light provoked
      an anxiolytic effect in both rat strains. The findings that neither different
      baseline levels of anxiety nor fear modulating light conditions were accompanied
      by changes in the performance of rats in the Morris water maze led us to the
      suggestion that there is no connection between anxiety and learning/memory in
      this task. Contrarily, anxiety might be associated with habituation learning in
      the open field test, shown by the superior habituation of the anxious FC rats in
      comparison to the less anxious WW rats. In sum, these results indicate that
      anxiety and learning/memory seem to be independently regulated behaviors, whereas
      habituation might be more closely correlated with anxiety. Nevertheless, a
      general statement about the relation between emotionality and learning/memory
      mechanisms would be premature and the link between behaviors remains to be
      clarified.

PMID- 12071663
TI  - Effects of hippocampal injections of a novel ligand selective for the alpha 5
      beta 2 gamma 2 subunits of the GABA/benzodiazepine receptor on Pavlovian
      conditioning.
AB  - Benzodiazepine pharmacology has led to greater insight into the neural mechanisms
      underlying learning and anxiety. The synthesis of new compounds capable of
      modulating responses produced by these receptors has been made possible by the
      development of an isoform model of the GABA(A)/benzodiazepine receptor complex.
      In the current experiment, rats were pretreated with several concentrations of
      the novel ligand RY024 (an alpha 5 beta 2 gamma 2 -selective benzodiazepine
      receptor inverse agonist) in the hippocampus and were trained in a Pavlovian fear
      conditioning paradigm. RY024 independently produced fear-related behavior prior
      to training and, at the highest concentration, decreased the strength of
      conditioning observed 24 h after training. These data provide further evidence
      for the involvement of hippocampal GABA(A)/benzodiazepine receptors in learning
      and anxiety.

PMID- 12071665
TI  - Context extinction and associative learning in Lymnaea.
AB  - Aerial respiratory behavior in the pond snail Lymnaea was operantly conditioned
      so that snails learned not to perform aerial respiration in a hypoxic
      environment. Snails were trained in either the standard context (no food odorant)
      or a carrot (food-odorant) context. An operant training procedure of two 45-min
      training sessions with a 1-h interval between the sessions followed by a third 45
      min training session 18 h later was sufficient to produce associative learning
      and long-term memory (LTM) that persisted for at least 5 days. If, however,
      following the third operant training session snails received three 45-min
      extinction training sessions, with each extinction session separated by at least
      a 1-h interval, LTM was not observed when tested the following day. That is, the
      memory was extinguished. Extinction, however, did not occur if the context of the
      extinction training was different from the context of the associative training.
      That is, in the snails trained in the standard context, extinction did not occur
      if the extinction training sessions were performed in the food-odorant context
      and vice versa.

PMID- 12071666
TI  - Laminar-dependent dendritic spine alterations in the motor cortex of adult rats
      following callosal transection and forced forelimb use.
AB  - Previously, the authors found that partial denervation of the motor cortex in
      adult animals can enhance this region's neuronal growth response to relevant
      behavioral change. Rats with partial corpus callosum transections that were
      forced to rely on one forelimb for 18 days had increased dendritic arborization
      of layer V pyramidal neurons in the opposite motor cortex compared to controls.
      This was not found as a result of denervation alone or of forced forelimb use
      alone. However, it seemed possible that each independent manipulation (i.e.,
      forced forelimb use alone and callosal transections alone) resulted in neural
      structural alterations that were simply not revealed in measurements of dendritic
      branch number and/or not inclusive of layer V dendrites. This possibility was
      assessed in the current study with a reexamination of the Golgi-Cox impregnated
      tissue generated in the previous study. Tissue was quantified from rats that
      received either partial transections of the rostral two-thirds of the corpus
      callosum (CCX) or sham operations (Sham) followed either by 18 days of forced use
      of one forelimb (Use) or unrestricted use of both forelimbs (Cont). Measurements
      of apical and basilar dendrites from pyramidal neurons of layer II/III and layer
      V were performed to detect spine addition resulting from either increased spine
      density or the addition of dendritic material. As hypothesized, significant spine
      addition was found following forced forelimb use alone (Sham+Use) and callosal
      transections alone (CCX+Cont). However, forced use primarily increased spines on
      layer II/III pyramidal neurons, whereas callosal transections primarily increased
      dendritic spines on layer V pyramidal neurons in comparison to Sham+Cont. A much
      more robust increase in layer V dendritic spines was found in animals with the
      combination of forced forelimb use and denervation (CCX+Use). In contrast to the
      effects of forced use alone, however, CCX+Use rats failed to show major net
      increases in spines on layer II/III neurons. These results indicate that while
      callosal denervation may greatly enhance the neuronal growth and synaptogenic
      response to behavioral change in layer V, it may also limit spine addition
      associated with forced forelimb use in layer II/III of the motor cortex.

PMID- 12071668
TI  - Hippocampus lesions impair landmark array spatial learning in homing pigeons: a
      laboratory study.
AB  - Hippocampal (HF)-lesioned pigeons display impaired homing ability when flying
      over familiar terrain, where they are presumably relying on a map-like
      representation of familiar landmarks to navigate. However, research carried out
      in the field precludes a direct test of whether hippocampal lesions compromise
      the ability of homing pigeons to navigate by familiar landmarks. To examine more
      thoroughly the relationship between hippocampus and landmark spatial learning,
      control, neostriatum-lesioned, and HF-lesioned homing pigeons were trained on two
      open field, laboratory, conditional discrimination tasks. One was a visual
      landmark array task, and the other was a room color discrimination task. For the
      tasks, the correct of three differently colored food bowls was determined by the
      spatial relationship among a group of five landmarks and room color,
      respectively. Intact control birds successfully learned both tasks, while
      neostriatum-lesioned birds successfully learned the landmark array task-the only
      task on which they were trained. By contrast, HF-lesioned birds successfully
      learned the room color task but were unable to learn the landmark array task. The
      data support the hypothesis that homing performance deficits observed in the
      field following hippocampal lesions are in part a consequence of an impairment in
      the ability of lesioned pigeons to use familiar visual landmarks for navigation.

PMID- 12071667
TI  - Associative learning acquisition and retention depends on developmental stage in
      Lymnaea stagnalis.
AB  - Associative learning dependent on visual and vestibular sensory neurons and the
      underlying cellular mechanisms have been well characterized in Hermissenda but
      not yet in Lymnaea. Three days of conditioning with paired presentations of a
      light flash (conditional stimulus: CS) and orbital rotation (unconditional
      stimulus: UCS) in intact Lymnaea stagnalis results in a whole-body withdrawal
      response (WBWR) to the CS. In the current study, we examined the optimal stimulus
      conditions for associative learning, including developmental stage, number of
      stimuli, interstimulus interval, and intertrial interval. Animals with a shell
      length longer than 18 mm (sexually mature) acquired and retained the associative
      memory, while younger ones having a shell length shorter than 15 mm acquired but
      did not retain the memory to the following day. For mature animals, 10 paired
      presentations of the CS and UCS presented every 2 min were sufficient for the
      induction of a WBWR to the CS. Furthermore, animals conditioned with the UCS
      presented simultaneously with the last 2 s of the CS also exhibited a significant
      WBWR in response to the CS. Blind animals did not acquire the associative memory,
      suggesting that ocular photoreceptors, and not dermal photoreceptors, detected
      the CS. These results show that maturity was key to retention of associative
      learning.

PMID- 12071669
TI  - A room with a view and a polarizing cue: individual differences in the stimulus
      control of place navigation and passive latent learning in the water maze.
AB  - We investigated individual differences in the stimulus control of navigational
      behavior in the water maze by comparing measures of place learning in one
      environment to measures of latent learning (via passive placement on the goal
      platform) in a novel environment. In the first experiment, 12 rats were trained
      to find a slightly submerged hidden platform at a fixed location in room A for 10
      days (4 trials/day). Fast and slow place learners were identified by their mean
      escape latency and cumulative distance to the goal during acquisition. The same
      animals were then given a 2-min passive placement on the submerged platform in
      room B. Latent learning was assessed by the animal's escape latency on a single
      swim trial immediately following the placement in room B. The results showed that
      the good latent learners in room B were not necessarily the fast place learners
      in room A. This weak correlation may be related to the fact that some rats swam
      near the area in room B that corresponded to the former goal location in room A
      relative to a common polarizing cue (i.e., the door/entrance to both rooms). When
      the view of the door was blocked in a second experiment a significant positive
      correlation between place acquisition and the latent learning test was obtained,
      although escape performance following passive placement was not improved. These
      findings suggest that while place navigation and latent learning via passive
      placement may involve some common cognitive-spatial function, other associative
      (S-S and/or S-R) processes that occur during place navigation/active movement may
      be required for animals to exhibit truly accurate navigational behavior
      characteristic of asymptotic escape performance in the water maze. Additional
      implications for neurobiological studies using a procedural pretraining design
      are discussed.

PMID- 12071670
TI  - Muscimol diffusion after intracerebral microinjections: a reevaluation based on
      electrophysiological and autoradiographic quantifications.
AB  - Intracerebral muscimol injection is widely used to inactivate discrete brain
      structures during behavioral tasks. However, little effort has been made to
      quantify the extent of muscimol diffusion. The authors report here
      electrophysiological and autoradiographic results obtained after muscimol
      injection (1 microg/microl) either into the nucleus basalis magnocellularis (0.1
      0.4 microl) or into the thalamic reticular nucleus (RE, 0.05-0.1 microl). In 52
      rats, multiunit recordings were collected either in the RE or in the auditory
      thalamus during the 2 h following muscimol injection. Decreases in neuronal
      activity were observed up to 3 mm from the injection site; their time of
      occurrence was a function of the distance between the injection and recording
      sites. Because these decreases cannot be explained by physiological effects, they
      likely reflected muscimol diffusion up to the recording sites. Autoradiographic
      studies involved 25 rats and different experimental conditions. Optical density
      (OD) measures indicated that after a survival time of 15 min, a 0.05 microl
      injection produced a labeled area of 5.25 mm(2) at the injection site and a
      rostrocaudal labeling of 1.7 mm. Increasing the survival time to 60 min, or
      increasing the injected volume to 0.1 microl, systematically led to a larger
      labeled area at the injection site (8-12 mm(2)) and to a larger rostrocaudal
      diffusion (2.0-2.5 mm). Direct quantifications of radioactivity by a high
      resolution radioimager validated the OD measures and even indicated a larger
      muscimol diffusion (up to 3.25 mm). Thus, these data point out that muscimol
      diffusion after intracerebral microinjection is larger than usually supposed. The
      relationships between these results and those obtained in behavioral studies are
      discussed.

PMID- 12071671
TI  - Antibody to amyloid beta protein alleviates impaired acquisition, retention, and
      memory processing in SAMP8 mice.
AB  - SAMP8 (senescence-accelerated mouse, P8 strain) mice overproduce amyloid
      precursor protein and beta-amyloid and have learning and memory deficits.
      Preliminary data have indicated that overproduction of beta-amyloid plays a role
      in the pathogenesis of acquisition and retention deficits in SAMP8 mice. In the
      studies reported here, the authors examined the effects of polyclonal and
      monoclonal antibodies to beta-amyloid on acquisition and retention in an aversive
      T-maze testing paradigm when injected intracerebroventricularly (ICV) into 12
      month SAMP8/TaJF mice. Both the polyclonal and monoclonal antibodies improved
      acquisition and retention when injected ICV 1 to 14 days prior to acquisition
      testing. Injection of all three antibodies intrahippocampally immediately
      following training improved retention on the T-maze when mice were tested 7 days
      later. The authors next studied the effect of monoclonal beta-amyloid antibody
      injected 48 h prior to training on the effect on retention in the T-maze of drugs
      modulating classical neurotransmitters. Arecoline and glutamate were injected
      directly into the hippocampus, and ketanserin, methiothepen, bicuculline, and OH
      saclofen were injected into the septum. Previously, the authors have found that
      the doses of these drugs required to improve retention are markedly altered in 12
      month SAMP8/TkJF mice compared to 4-month P8 mice. In these studies, it was
      demonstrated that antibody to beta-amyloid resulted in these drugs improving
      retention at doses that improved memory in 4-month SAMP8/TaJF mice. Based on
      these findings, we conclude that beta-amyloid overproduction is at least in part
      responsible for the acquisition and memory deficits in 12-month-old SAMP8/TaJF
      mice. Antibody to beta-amyloid restores the retention response to
      neurotransmitter manipulation to that seen in 4-month-old mice. beta-amyloid
      appears to play a key role in the loss of acquisition and retention seen in
      SAMP8/TaJF mice.

PMID- 12071672
TI  - Place learning in scopolamine-treated rats: the roles of distal cues and
      catecholaminergic mediation.
AB  - Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists
      impair place learning in a water maze by interfering with the processing of
      distal, visual cues. Extramaze cues were offered to rats in the form of
      geometrical patterns arranged on the inner circumference of a curtain surrounding
      the water maze. In Experiment 1 the animals were offered both the distal cues and
      proximal cues in the form of pingpong balls in fixed positions on the surface of
      the water while only distal cues were present in Experiment 2. Animals were
      injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to
      the daily place learning sessions. Upon reaching criterion level performance the
      animals were tested on "rotation" sessions on which the distal cues were
      displaced. The outcome of such "rotations" demonstrated that-regardless of the
      presence or absence of proximal cues-scopolamine-treated rats relied at least as
      much as normal animals on the distal cues. The acquisition phase of both
      Experiments 1 and 2 demonstrated an almost complete lack of scopolamine
      associated impairment in acquisition and performance of the place learning task.
      In Experiment 3 (when scopolamine was no longer administered) the subjects of
      Experiment 2 were exposed to a series of pharmacological "challenges" of their
      place learning performance and eventually to surgical ablation of the
      anteromedial prefrontal cortex. The outcome of the pharmacological challenges and
      the postoperative test of task performance demonstrated that the place learning
      performance of animals which had acquired the task under scopolamine was mediated
      by a neural substrate dissimilar to the substrate of task performance in normal
      animals. Rats acquiring the task while deprived of the cholinergic system
      demonstrated above-normal contributions to task mediation from catecholaminergic
      probably dopaminergic-mechanisms and tentative results pointed to a "shift"
      toward prefrontal task mediation.

PMID- 12071673
TI  - Low body temperature, time dilation, and long-trace conditioned flavor aversion
      in rats.
AB  - Conditioned flavor aversion was examined in Wistar-derived albino rats that were
      immersed in cold water for 0, 2.5, 5, or 10 min immediately following 10-min
      exposure to a.1% saccharin solution and given an intraperitoneal (i.p.) injection
      of 0.15 M lithium chloride (LiCl) either 90, 135, 180, or 225 min later. Cold
      water immersion for 2.5, 5, and 10 min led to body temperature decreases of
      approximately 4.5, 7, and 10 degrees C, respectively. Rats whose body
      temperatures were not reduced (0 min immersion) showed no saccharin aversion when
      the LiCl was delayed 90 min. Rats whose body temperatures were reduced 4.5, 7,
      and 10 degrees C displayed conditioned aversions at LiCl delays up to 135, 180,
      and 225 min, respectively. These results were interpreted in terms of a cold
      induced slowing of a biochemical clock that may uniquely govern specific timing
      processes involved in associative learning over long delays, such as long-trace
      conditioned flavor aversion, learned safety, and certain types of learning that
      involve an extensive time lapse (e.g., extinction of fear).

PMID- 12071674
TI  - Effects of pretraining intrastriatal administration of p-chloroamphetamine on
      inhibitory avoidance.
AB  - Pretraining systemic administration of p-chloroamphetamine (PCA) consistently
      produces retention deficits of inhibitory avoidance. This drug causes a
      widespread acute release of serotonin from cerebral neuronal terminals, but it is
      not known where in the brain PCA exerts its disruptive cognitive effects. The
      present experiment was aimed at determining whether the striatum is a site of
      action of this drug. PCA (5 microg) was infused, bilaterally, into the striatum
      of rats at 30, 15, or 5 min before training of inhibitory avoidance, and
      retention of the task was measured 24 h later. An inversely related time
      dependent deficit was found. Together with the results from appropriate control
      groups, this result strongly suggest that systemic PCA produces its reported
      cognitive effects, at least in part, through its pharmacological action within
      the striatum.

PMID- 12071675
TI  - A role for olfaction in object recognition by normal and hippocampal-damaged
      rats.
AB  - To examine how olfactory and visual factors affect object discriminations in rats
      with and without hippocampus damage, the authors trained Long-Evans rats on
      simple object discriminations. They then examined how these discriminations were
      affected by rotations of the objects, by coating the objects in a transparent
      acrylic coating, or by both rotating and coating the objects in acrylic. The rats
      displayed no impairments when the objects were only sprayed in acrylic, and they
      displayed minor impairments when the objects were rotated. However, when the
      objects were both rotated and acrylic coated, the rats displayed severe
      impairments. This suggests that the rats are solving the rotated-only phase based
      on surface features of the objects (probably odor) and not based on the visual
      information. Such species' biases for obtaining object information are important
      factors to consider when designing and interpreting visual memory experiments
      across species. There was no difference in performance between the rats with
      hippocampus damage and the sham rats, and this is consistent with the literature
      on similar tasks.

PMID- 12071676
TI  - Inhibition of monoADP-ribosylation prevents long-term memory consolidation of a
      single-trial passive avoidance task in the day-old chick.
AB  - The cytosolic posttranslational protein-modifying mechanism of monoADP
      ribosylation has been implicated in long-term potentiation, a synaptic model of
      memory formation. The current study investigated the effect of inhibiting
      mono(ADP-ribosyl) transferase on memory for the passive avoidance task in day-old
      chicks (white Leghorn-black Australorp). Various doses of novobiocin or menadione
      sodium bisulfite were administered intracranially at different times before or
      after training. Control chicks were administered saline at matched times.
      Novobiocin (650 microM) or menadione sodium bisulfite (250 microM) administered
      between 5.0 min pretraining and 2.5 min posttraining was found to cause a
      persistent loss of retention from 120 min posttraining. These data provide the
      first demonstration that monoADP-ribosylation is required for the maintenance of
      long-term memory. Furthermore, the temporal characteristics of the memory loss
      caused by monoADP-ribosylation inhibition appears to exclude this mechanism as a
      downstream effect of the well-established nitric oxide activity previously shown
      to occur within 40 min of passive avoidance training.

PMID- 12071677
TI  - Migration of Salmonella typhimurium --harboring bone marrow--derived dendritic
      cells towards the chemokines CCL19 and CCL21.
AB  - Macrophages are considered as main cellular target encountered by the facultative
      intracellular bacterium Salmonella typhimurium. However, in orally infected mice
      these pathogens are first internalized by dendritic cells (DCs) that are located
      in the subepithelial dome of Peyer's patches. Moreover, DCs can penetrate the
      intestinal epithelium to sample bacteria. Here, we examined the interaction of
      Salmonella with bone marrow-derived DCs (BM-DCs). In order to study the role of
      DCs as vehicles for the dissemination of Salmonella, an in vitro model was
      established. In this model, Salmonella -activated BM-DCs enhanced surface
      expression of MHC class II and co-stimulatory molecules. We found that, upon
      maturation, BM-DCs upregulated chemokine receptor 7 (CCR7) mRNA and surface
      molecule expression. Salmonella -exposed DCs as well as mature DCs, but not
      immature DCs, were recruited towards the CC chemokines CCL19 and CCL21, two
      ligands of CCR7. The maturation process of DCs did neither require bacterial
      internalization nor viability. About one third of the migrated BM-DCs harbored
      intracellular bacteria, whereas the remaining two third did not contain bacteria.
      Salmonella, but not an apathogenic E. coli laboratory strain was capable to
      survive within BM-DCs. Taken together, our data implicate that DCs are first
      activated and subsequently utilized as carriers by Salmonella.

PMID- 12071678
TI  - Inhibition of in vitro cell adherence of Clostridium difficile by Saccharomyces
      boulardii.
AB  - The influence on the adherence of Clostridium difficile to Vero cells of the
      yeast Saccharomyces boulardii, the yeast fractions (cytoplasm and cell wall) and
      the culture supernatant was investigated in vitro. C. difficile adherence was
      significantly inhibited when bacteria were pre-incubated with the whole yeast and
      the cell wall fraction; this adherence inhibition was dose-dependent. The cell
      wall fraction also acts upon the target cultured cells inasmuch as the level of
      adherence was significantly decreased when Vero cells were preincubated with it.
      The same experiments carried out in the presence of an inhibitor of serine
      proteases resulted in no inhibition of bacterial adherence. These results suggest
      that the yeast could inhibit adherence of C. difficile to cells thanks to its
      proteolytic activity but also through steric hindrance.

PMID- 12071679
TI  - Anti-V antigen antibody protects macrophages from Yersinia pestis -induced cell
      death and promotes phagocytosis.
AB  - The pathogenic Yersinia spp. harbor a common plasmid (pYV) essential for
      virulence. The plasmid encodes a type III secretion system that functions to
      translocate Yersinia outer proteins (Yops) into the host cytosol. Within the host
      cell, the Yops act to inhibit phagocytosis and induce apoptosis. One of the
      plasmid-encoded proteins, virulence antigen (V), is a major protective immunogen
      that is involved in Yop translocation. Yersinia pestis, like the enteric Yersinia
      spp., was both resistant to phagocytosis by and cytotoxic for J774.A1, a murine
      macrophage cell line. Both of these activities were dependent on culture of the
      bacteria at 37 degrees C for 1.5-2 h before infection. However, extending the
      preculture period at 37 degrees C to 24 h, which induced formation of a capsule,
      completely blocked cytotoxicity. Treating the bacteria with either rabbit
      polyclonal anti-V antibodies (R anti-V) or monoclonal antibody (MAb) 7.3,
      antibodies specific for V and protective against plague in vivo, protected
      J774.A1 cells from Y. pestis -induced cell death and also reversed the inhibition
      of phagocytosis. Whereas protection against cell cytotoxicity was afforded by the
      F(ab')(2) portion of R anti-V, the ability of anti-V to induce uptake of Y.
      pestis appeared to be dependent on the Fc portion of the Ab. The protective
      epitope(s) recognized by R anti-V was contained in the central region of Y.
      pestis V (aa 135-275) and were partially cross reactive with Y.
      pseudotuberculosis and Y. enterocolitica serotype 08 V antigens.

PMID- 12071680
TI  - Brucella abortus siderophore 2,3-dihydroxybenzoic acid (DHBA) facilitates
      intracellular survival of the bacteria.
AB  - Siderophores are low molecular weight molecules that allow bacteria to acquire
      iron from host cell proteins. 2,3-dihydroxybenzoic acid (DHBA) is the only known
      siderophore produced by the intracellular pathogen Brucella abortus. Here its
      role in virulence was assessed by evaluating the ability of a mutant with a
      disruption of the entC gene to survive and replicate in vitro in murine and
      bovine cells and in vivo in resistant and susceptible murine hosts. It was
      hypothesized that DHBA is vital for bacterial virulence by its ability to chelate
      intracellular iron thereby preventing generation of anti-bacterial hydroxyl
      radicals via the Haber-Weiss reaction, to scavenge reactive oxygen intermediates
      and for acquisition of iron needed for nutritional purposes. The data showed DHBA
      played a significant role for bacterial survival in host cells after infection
      including in murine macrophages cultured in the presence and absence of exogenous
      interferon-gamma (IFN-gamma) and in bovine trophoblasts supplemented with
      erythritol. In severely iron-depleted conditions, DHBA was also found to be
      essential for growth in murine macrophages. Despite these deficiencies, the
      absence of DHBA had no long-term significant effect on the number of CFU
      recovered in vivo from either the Brucella-resistant C57BL/6 mice or Brucella
      susceptible IFN-gamma knock-out C57BL/6 mice.

PMID- 12071681
TI  - Identification of a general secretory pathway in a human isolate of Burkholderia
      vietnamiensis (formerly B. cepacia complex genomovar V) that is required for the
      secretion of hemolysin and phospholipase C activities.
AB  - Members of the Burkholderia cepacia complex can secrete proteases, lipases, and
      hemolysins. We report in this study the identification of a general secretory
      pathway present in a B. vietnamiensis (formerly genomovar V) clinical isolate,
      which is required for the efficient secretion of phospholipase C and hemolysin
      activities. Southern blot hybridization experiments revealed that this general
      secretion pathway is highly conserved among the different genomovars of the B.
      cepacia complex and is homologous to a similar system described in B.
      pseudomallei. We also show that this pathway appears not to be necessary for
      intracellular survival of B. vietnamiensis within Acanthamoeba polyphaga.

PMID- 12071682
TI  - Protection for the good: subcategorization reduces hedonic contrast.
AB  - Stimuli are rated less "good" when compared to very good context stimuli than
      when presented alone or compared to less good context stimuli. This diminution in
      rating is hedonic contrast. In two studies, degree of hedonic contrast depended
      on subjects' categorization of stimuli. Subjects were surveyed about their liking
      of gourmet and ordinary coffees (Study 1) and specialty and regular beers (Study
      2). In Study 1, contrast was substantially smaller for subjects who regarded the
      coffees as belonging to different categories than for subjects having a common
      category for both sorts of coffees. The analogous phenomenon was found in Study
      2, comparing subjects who subcategorized beers to subjects who had a common
      category for both sorts of beers. Contrast is greatest for stimuli in a common
      category.

PMID- 12071683
TI  - Influence of environmental temperatures during gestation and at birth on eating
      characteristics in adolescence: a replication and extension study.
AB  - Past research has shown a season of birth effect in clinical subjects with eating
      disorders. Studies also indicate a similar effect of environmental temperatures
      in non-clinical subjects, as well as effects of environmental temperatures during
      the three trimesters of gestation. These two studies aimed to replicate and
      extend those findings. The participants were adolescents (ages 15-19 years) who
      attended public schools in a mid-Atlantic US city. They completed the relevant
      scales of the Eating Disorder Inventory (N=578) and the Three Factor Eating
      Questionnaire (N=191). Correlational analyses were employed to study the
      relationship of environmental temperatures during pregnancy (the three trimesters
      of intrauterine development and at birth) with eating characteristics. The
      results of the previous studies were broadly replicated in Study 1, but Study 2
      revealed a difference in the pattern of associations according to the measure
      used. This contrast indicates that the way in which one conceptualizes eating
      pathology is of critical importance in understanding the long-term impact upon
      eating patterns of environmental temperature during the intrauterine period.
      Possible theoretical bases for these findings are discussed.

PMID- 12071684
TI  - Public perception of a range of potential food risks in the United Kingdom.
AB  - This study aimed to use a standard questionnaire to obtain a nationally
      representative sample of opinions on a range of potential food risks.
      Participants were a national sample of 1182 subjects selected using three
      different approaches: random and sentinel postal samples and a telephone survey.
      A modified psychometric questionnaire (the Perceived Food Risk Index) was
      administered to subjects on three occasions, spanning five time-points. Baseline
      data collection was undertaken from October to December 1998 (phase 1). The
      second wave of data collection was undertaken over three time-points in February,
      April and July 1999 (one-third of respondents to phase 1 at each time-point -
      data combined as phase 2), and the final phase of data collection was between
      October and December 1999 (phase 3). Principal components analysis was used to
      assess the intercorrelations between the items on the questionnaire. Two main
      components were identified as 'dread' and 'knowledge'. Saturated fats were
      perceived as the least dreaded and the most known of the potential risks
      considered, while bovine spongiform encephalopathy and Salmonella were the risks
      dreaded the most. There was a slight perception that the potential risks had
      become more known over the year, especially for growth hormones. This study has
      raised a number of important issues for risk communicators. Despite current
      policy aimed at reducing fat intake, this will be difficult to achieve at a
      population level since people are not worried about its impact, yet food safety
      continues to be a significant concern to the public.

PMID- 12071685
TI  - Source of food safety information: whom do adolescents trust?

PMID- 12071686
TI  - Relation between PROP (6-n-propylthiouracil) taster status, taste anatomy and
      dietary intake measures for young men and women.
AB  - Previous studies have related 6-n-propylthiouracil (PROP) taster status to
      preference for, and consumption of various (bitter-tasting) foods recognized for
      their cancer-preventive properties. The aim of this study was to examine PROP
      taster status in relation to general measures of dietary intake as well as the
      consumption of specific food groups. College students (n=183) were classified as
      non-tasters (n=49), medium tasters (n=89) and supertasters (n=45) of PROP based
      on intensity ratings of NaCl and PROP solutions. Dietary intake measures were
      derived from a food frequency questionnaire and body mass indices (BMI) were
      derived from self-reported height and weight. Supertasters had higher fungiform
      papillae counts on the anterior tongue than tasters and non-tasters, yet the
      distributions of papillae counts overlapped across PROP taster groups. No
      significant differences were found for BMI values and energy intake among taster
      groups. PROP-tasting women derived a greater percentage of their dietary energy
      from fat, and consumed less fruit than non-tasters. PROP supertasters did not
      differ from tasters and non-tasters in intake of bitter fruits, vegetables or
      beverages except for a lesser intake of green salad. The hypothesis that PROP
      supertasters, through heightened sensitivity to, and avoidance of, bitter-tasting
      fruits, vegetables and other foods with antioxidant properties, may therefore be
      at increased risk for diet-linked diseases such as cancer, is not supported by
      these findings.

PMID- 12071687
TI  - "You will eat all of that!": a retrospective analysis of forced consumption
      episodes.
AB  - The present research was initiated to examine the prevalence of forced
      consumption and its role in subsequent food rejection. A forced consumption
      episode was defined as a situation where Person(s) A forced or demanded Person B
      to consume a specific substance against Person B's will. An initial survey of 407
      college students revealed that over 69% of them had experienced at least one
      forced consumption episode. One hundred forty individuals completed a follow-up
      questionnaire exploring various characteristics of their most memorable forced
      consumption scenario. Specifically, the most common type of forced consumption
      (76%) involved an authority figure (e.g. parent, teacher) forcing a child to
      consume a novel, disliked, or aversive food. In this authority figure scenario,
      respondents recalled the episode as involving interpersonal conflict and negative
      affect, and identified the most aversive aspects of this scenario as lack of
      control and feelings of helplessness. Furthermore, most respondents (72%)
      reported that they would not willingly eat the target food today. In sum, the
      forced consumption episode appears to be a unique situation in which distasteful
      food combines with interpersonal conflict to result in long-lasting food
      rejection.

PMID- 12071688
TI  - Effects of chronic amphetamine on the appetitive and consummatory phases of
      feeding.

PMID- 12071690
TI  - Chewing gum selectively improves aspects of memory in healthy volunteers.

PMID- 12071689
TI  - Habituation of responding for food in humans.
AB  - Habituation to repeated food stimuli has been demonstrated in various response
      systems across animals and humans. Patterns of responding to obtain food
      demonstrate many empirical characteristics of habituation, and the purpose of the
      present study was to determine whether motivated responding for food in humans
      follows an habituation pattern. Thirty-five nonobese men were randomized to
      groups in which they responded to gain access to repeated presentations of the
      same food or presentations of a variety of isocaloric food. Subjective ratings of
      food liking and hunger were assessed. Consistent with habituation theory,
      participants working for one type of food demonstrated a more rapid decrease in
      responding for food and in ratings of liking of the repeatedly presented food
      than participants working for varied foods. All participants showed similar
      reductions of hunger and resumed responding for a novel food stimulus. This study
      documents that motivated responding for food in human shares characteristics of
      an habituation process.

PMID- 12071691
TI  - How visibility and convenience influence candy consumption.

PMID- 12071692
TI  - High throughput methods for gene cloning and expression.
AB  - We outline a high throughput process for the production of bacterial expression
      clones using automated liquid handlers. The protocol consists of a series of
      interlinked methods representing liquid manipulations or incubations on various
      stations of the automation system. The methods employ the ligation-independent
      cloning approach that enables the simultaneous production of plasmids for
      different expression systems. The current cloning protocol spans 3 days with a
      linear throughput of 400 targets per production run. This automated approach
      enables the production of large numbers of bacterial expression clones and
      ultimately purified proteins. Although they were developed for structural
      genomics, these molecular protocols can also be applied in high throughput
      strategies such as those used for site-specific mutagenesis or protein
      interaction studies.

PMID- 12071693
TI  - A new vector for high-throughput, ligation-independent cloning encoding a tobacco
      etch virus protease cleavage site.
AB  - To establish high-throughput methods for protein crystallography, all aspects of
      the production and analysis of protein crystals must be accelerated. Automated,
      plate-based methods for cloning, expression, and evaluation of target proteins
      will help researchers investigate the vast numbers of proteins now available from
      sequenced genomes. Ligation-independent cloning (LIC) is well suited to robotic
      cloning and expression, but few LIC vectors are available commercially. We have
      developed a new LIC vector, pMCSG7, that incorporates the tobacco etch virus
      (TEV) protease cleavage site into the leader sequence. This protease is highly
      specific and functions under a wide range of conditions. The new vector
      incorporates an N-terminal his-tag followed by the TEV protease recognition site
      and a SspI restriction site used for LIC. The vector functioned as expected,
      giving high cloning efficiencies and strong expression of proteins. Purification
      and cleavage of a target protein showed that the his-tag and the TEV cleavage
      site function properly. The protein was purified and cleaved under different
      conditions to simulate both plate-based screening methods and large-scale
      purifications for crystal production. The vector also includes a pair of
      adjacent, unique restriction sites that will allow insertion of additional
      modules between the his-tag and the cleavage site of the leader sequence to
      generate a family of vectors suitable for high-throughput production of proteins.

PMID- 12071694
TI  - Expression and purification of the recombinant enteropathogenic Escherichia coli
      vaccine candidates BfpA and EspB.
AB  - BfpA, the structural repeating protein subunit A of the bundle-forming pilus and
      EspB, a type-III-secreted pore-forming protein of enteropathogenic Escherichia
      coli (EPEC), both virulence factors central for EPEC pathogenesis, were
      overexpressed in E. coli DH5alpha and M15 laboratory strains, respectively, using
      the pQE-30 cloning expression system, as chimeric fusions to a NH(2)-terminal
      histidine hexapeptide (His(6)-tag) sequence. After isopropyl beta-d
      thiogalactoside induction, the expression levels achieved were 11 and 40% of
      total soluble protein for BfpA and EspB, respectively. The His(6)-tagged
      recombinant proteins were purified (up to 98% homogeneity) by Ni-agarose affinity
      chromatography and produced yields varying from 0.65 to 3.1 mg of recombinant
      protein per gram of wet weight cells. The immunogenicity and antigenicity of the
      final products were tested in rabbits and using fecal specimens obtained from
      children suffering from acute watery diarrhea, respectively. The recombinant
      products correspond to antigenically authentic protein standards, useful in
      future epidemiological and neonatal vaccinology studies.

PMID- 12071695
TI  - In vitro assembly, purification, and crystallization of the rab geranylgeranyl
      transferase:substrate complex.
AB  - Posttranslational modification with the geranygeranyl moiety is essential for the
      ability of Rab GTPases to control processes of membrane docking and fusion. This
      modification is conferred by Rab geranylgeranyltransferase (RabGGTase), which
      catalyzes the transfer of two 20-carbon geranylgeranyl groups from geranylgeranyl
      pyrophosphate onto C-terminal cysteine residues of Rab proteins. The enzyme
      consists of a catalytic alpha/beta heterodimer and an accessory protein termed
      Rab escort protein (REP-1) that delivers the newly prenylated Rab proteins to
      their target membrane. In order to understand the structural basis of Rab
      prenylation, we have investigated in vitro assembly and crystallization of the
      RabGGTase:REP-1:Rab complex. In order to ensure maximal stability of the ternary
      complex, we generated its monoprenylated form, which corresponds to a reaction
      intermediate and displays the highest affinity between the components. This was
      achieved by expressing the individual components in baculovirus and Escherichia
      coli systems with subsequent purification followed by in vitro monoprenylation of
      Rab7 with immobilized recombinant RabGGTase. Purified monoprenylated REP-1:Rab7
      was complexed with recombinant RabGGTase and crystallized in hanging drops. The
      crystals obtained initially diffract to 8 A on an in-house X-ray source.

PMID- 12071696
TI  - Optimization of baculovirus-mediated expression and purification of hexahistidine
      tagged murine DNA (cytosine-C5)-methyltransferase-1 in Spodoptera frugiperda 9
      cells.
AB  - Enzymatic DNA methylation of carbon 5 of cytosines is an epigenetic modification
      that plays a role in regulating gene expression, differentiation, and
      tumorigenesis. DNA (cytosine-C5)-methyltransferase-1 is the enzyme responsible
      for maintaining established methylation patterns during replication in mammalian
      cells. It is composed of a large ( approximately 1100 amino acids (a.a.)) amino
      terminal region containing many putative regulatory domains and a smaller (
      approximately 500 a.a.) carboxy-terminal region containing conserved, catalytic
      domains. In this study, murine DNA (cytosine C5)-methyltransferase-1, fused to an
      amino-terminal hexahistidine tag, was expressed by infecting Spodoptera
      frugiperda cells for 46 h with a recombinant baculovirus carrying the DNA
      (cytosine-C5)-methyltransferase-1 cDNA. A total of 3 x 10(8) infected S.
      frugiperda cells yielded approximately 1 mg of full-length, hexahistidine-tagged
      DNA (cytosine-C5)-methyltransferase-1, which was purified approximately 450-fold
      from RNase-treated S. frugiperda cell extracts by nickel affinity chromatography.
      The characterization of hexahistidine-tagged DNA (cytosine-C5)-methyltransferase
      1 through DNA methylation and inhibitor-binding assays indicated that the
      purified enzyme had at least a 30-fold higher catalytic efficiency with
      hemimethylated double-stranded oligodeoxyribonucleotide substrates than
      unmethylated substrates and was most active with small oligodeoxyribonucleotide
      substrates with a capacity for forming stem-loop structures. The expression and
      purification procedures reported here differ significantly from the original
      reports of baculovirus-mediated hexahistidine-tagged DNA (cytosine-C5)
      methyltransferase-1 expression and purification by nickel affinity chromatography
      and provide a consistent yield of active enzyme.

PMID- 12071698
TI  - Purification of alpha-sarcin and an antifungal protein from mold (Aspergillus
      giganteus) by chitin affinity chromatography.
AB  - A simple method for preparation of alpha-sarcin and an antifungal protein (AFP)
      from mold (Aspergillus giganteus MDH 18894) has been developed. alpha-Sarcin and
      AFP were purified simultaneously by chitin affinity column chromatography and gel
      filtration. By this method, 4.5 mg of pure alpha-sarcin and 6.9 mg of pure AFP
      were obtained from 2 liters of culture medium. Compared with other purification
      methods such as ion-exchange column chromatography, this procedure was very
      simple and specific. The purified alpha-sarcin and AFP were homogeneous as
      characterized by SDS-polyacrylamide gel electrophoresis. Both alpha-sarcin and
      AFP exhibited the binding activity to generated chitin. Soluble glycochitin
      decreased the intensity of fluorescence of alpha-sarcin and made the lambda(em)m
      shift from 340 to 347 nm. Titration of alpha-sarcin with N-bromosuccinimide under
      native conditions revealed that two tryptophans (Trps) were all located in the
      core part of alpha-sarcin molecule. This indicated that Trps were not involved in
      the binding of alpha-sarcin to chitin. Glycochitin in the culture medium
      increased the expression of alpha-sarcin, while it had no effect on the
      expression of AFP. Unlike other ligands such as Cibacron blue for the affinity
      purification of alpha-sarcin and AFP, glycochitin increased the nuclease activity
      of alpha-sarcin.

PMID- 12071697
TI  - Expression, characterization, and purification of recombinant porcine lactoferrin
      in Pichia pastoris.
AB  - Recombinant porcine lactoferrin (rPLF) was synthesized in Pichia pastoris using a
      constitutive promoter from the glyceraldehyde-3-phosphate dehydrogenase gene.
      Strains expressing rPLF with its own signal sequence or with that from the yeast
      alpha-mating factor (alpha-MF) were able to produce and secrete rPLF, but levels
      were consistently higher using alpha-MF constructs. In contrast, P. pastoris
      strains that expressed rPLF without a signal sequence produced the protein in an
      insoluble intracellular form. Increasing the initial pH of shake-flask culture
      medium from 6.0 to 7.0 or adding ferric ions to the medium (to 100 microM)
      resulted in significant improvements in expression of rPLF from P. pastoris.
      Expression levels (approximately 12 mg/L) were much higher than those observed
      from Saccharomyces cerevisiae strains (1-2 mg/L). P. pastoris-secreted rPLF was
      isolated and purified via a one-step simple procedure using a heparin column. The
      molecular size (78 kDa), isoelectric point (8.8-9.0), N-terminal amino acid
      sequence, and iron-binding capability of rPLF were each similar to that of native
      milk PLF.

PMID- 12071699
TI  - Crocodilian tau-crystallin: overexpression, purification, and characterization.
AB  - tau-Crystallin is a taxon-restricted crystallin found in eye lenses of reptiles
      and a few avian species but presumably absent in mammals. The level of tau
      crystallin in the lens varies among different species. In the crocodile lens, it
      is the least abundant crystallin and is present in trace amounts. We present a
      method for cloning, overexpression, and purification of crocodilian tau
      crystallin utilizing a combination of gel filtration and ion-exchange
      chromatography yielding an extremely purified protein. The protein gets profusely
      expressed resulting in a fairly high yield and exists as a monomeric entity of
      47.5 kDa molecular mass. The recombinant tau-crystallin exists in a properly
      folded native state as probed by circular dichroism and fluorescence spectroscopy
      and exhibits enolase activity.

PMID- 12071700
TI  - Purification and characterization of recombinant Plasmodium falciparum
      adenylosuccinate synthetase expressed in Escherichia coli.
AB  - Most parasitic protozoa lack the de novo purine biosynthetic pathway and rely
      exclusively on the salvage pathway for their purine nucleotide requirements.
      Enzymes of the salvage pathway are, therefore, candidate drug targets. We have
      cloned the Plasmodium falciparum adenylosuccinate synthetase gene. In the
      parasite, adenylosuccinate synthetase is involved in the synthesis of AMP from
      IMP formed during the salvage of the purine base, hypoxanthine. The gene was
      shown to code for a functionally active protein by functional complementation in
      a purA mutant strain of Escherichia coli, H1238. This paper reports the
      conditions for hyperexpression of the recombinant protein in E. coli BL21(DE3)
      and purification of the protein to homogeneity. The enzyme was found to require
      the presence of dithiothreitol during the entire course of the purification for
      activity. Glycerol and EDTA were found to stabilize enzyme activity during
      storage. The specific activity of the purified protein was 1143.6 +/- 36.8
      mUnits/mg. The K(M)s for the three substrates, GTP, IMP, and aspartate, were
      found to be 4.8 microM, 22.8 microM, and 1.4 mM, respectively. The enzyme was a
      dimer on gel filtration in buffers of low ionic strength but equilibrated between
      a monomer and a dimer in buffers of increased ionic strength.

PMID- 12071701
TI  - Expression of recombinant human betaine: homocysteine S-methyltransferase for x
      ray crystallographic studies and further characterization of interaction with S
      adenosylmethionine.
AB  - Elevated homocysteine as a result of dysfunctional metabolic enzymes is an
      independent risk factor for arteriosclerosis. Betaine:homocysteine S
      methyltransferase (BHMT) (EC 2.1.1.5) is an important enzyme in the pathway of
      homocysteine metabolism in that it recycles methionine from homocysteine and
      nonfolate methyl donors. To initiate X-ray crystallographic structural studies,
      we created a BHMT expression construct for use in Escherichia coli that has a
      polyhistidine purification tag with no extraneous protein, usually found in
      commercial vectors, between the tag and protein sequence. The extra amino acids
      can hinder the crystallization process. A modified pET28b vector was designed to
      produce N-terminal polyhistidine-tagged proteins with a simple construction
      scheme having broad applicability because of the use of rare SapI cloning sites.
      BHMT expressed using this vector could be rapidly purified using metal chelate
      chromatography. Gel exclusion chromatography analysis showed that recombinant
      polyhistidine-tagged human BHMT is a tetramer. S-Adenosylmethionine (SAMe) has no
      effect on the recombinant BHMT's ability to methylate homocysteine nor does the
      enzyme appear to bind SAMe when examined by microcalorimetry.

PMID- 12071702
TI  - Expression and purification of two hydrophobic double-spanning membrane proteins
      derived from the cystic fibrosis transmembrane conductance regulator.
AB  - We describe a rapid method for the expression and purification of two hydrophobic
      protein constructs derived from the membrane domain of the cystic fibrosis
      transmembrane conductance regulator (CFTR), the protein associated with cystic
      fibrosis. The proteins have no sequence homology but are both predicted to
      contain two membrane-spanning segments. The protocol involves the expression of
      CFTR constructs as thioredoxin fusion proteins in Escherichia coli, followed by
      partial purification by affinity chromatography, removal of the thioredoxin
      moiety by proteolytic cleavage in the presence of detergent, and final
      purification by reversed-phase high-performance liquid chromatography. The method
      yields milligram amounts of purified constructs that spontaneously insert into
      detergent micelles in alpha-helical conformation. We predict that this protocol
      will be applicable to a variety of proteins of similar size and hydrophobicity.

PMID- 12071703
TI  - Large-scale purification and characterization of malaria vaccine candidate
      antigen Pvs25H for use in clinical trials.
AB  - The budding yeast Saccharomyces cerevisiae has been used to express the
      recombinant protein Pvs25H, currently the only candidate transmission-blocking
      vaccine against Plasmodium vivax malaria. This molecule contains four epidermal
      growth factor-like domains and is expressed as at least two stable monomeric
      forms with different physicochemical properties. Pvs25H-A is apparently
      homogeneous and seems to have a correct disulfide bond structure. By contrast,
      Pvs25H-B is produced as a heterogeneous population of molecules, some of which
      are associated with an as yet unidentified chromophore, and it contains both
      internal and N-terminal cleavages. We report here a procedure for successfully
      separating these two forms with a process suitable for clinical production of
      this antigen.

PMID- 12071704
TI  - Large-scale expression and purification of high-molecular-weight glutenin
      subunits.
AB  - The high-molecular-weight glutenin subunits (HMW-GSs) are considered to be one of
      the most important components of wheat gluten, contributing to the unique
      viscoelastic properties of wheat dough. The HMW-GSs are highly homologous in
      sequence and structure and a mixture of subunits is usually present in wheat
      flours. Consequently, it is difficult to purify these proteins separately in
      appreciable amounts. Expression in heterologous systems provides a clear
      opportunity to produce large amounts of single HMW-GS proteins, amounts (up to
      100 mg) which are required for in vitro analysis of these proteins. However,
      since the first expression studies of HMW-GSs, over 10 years ago, this technology
      has not been widely utilized. Previous studies have been analytical or small
      scale (5-100 ml) and in most cases only partial purity was obtained. In the
      present paper, we describe in detail the expression of the HMW-GSs Glu1-Dx2, Dx5,
      Dy10, and Dy12 for the first time on a large scale, producing up to 100 mg of
      target protein from a 2-liter bacterial culture, using a Biostat fermenter. Our
      results include optimization of expression conditions to increase yield and
      stability of proteins. Results also include localization, differences between x-
      and y-type expression and small-scale versus large-scale expression. We also
      developed a large-scale purification procedure. The bacterially expressed
      proteins have the same molecular weight on SDS-PAGE and the same retention times
      on RP-HPLC as their native counterparts extracted from flour. Functionality
      tests, on the bacterially produced proteins, have shown a clear correlation with
      the equivalent native proteins from flour. These results provide a clear
      opportunity to produce protein in amounts necessary for more detailed studies of
      the structure and function of the HMW-GSs and glutenin polymers on dough
      development and quality.

PMID- 12071705
TI  - Expression, refolding, purification, molecular characterization, crystallization,
      and preliminary X-ray analysis of the receptor binding domain of human B7-2.
AB  - The cell-mediated immune response involves a series of specific molecular
      interactions between cell surface molecules on T cells and antigen-presenting
      cells. Of particular importance for the regulation of T cell activity is the
      interaction of the B7 isoforms, B7-1 and B7-2, with the T cell surface
      costimulatory receptors, CD28 and CTLA-4. The binding of CD28 by B7-1/B7-2
      results in an enhancement of T cell responses initiated by the interaction
      between a clonotypic T cell receptor and its specific, antigenic MHC-peptide
      complex, whereas the subsequent engagement of CTLA-4 by B7-1/B7-2 leads to a down
      regulation of the response. Here we report the expression, refolding,
      purification, characterization, and crystallization of the receptor-binding
      domain of human B7-2. The receptor-binding domain of human B7-2 was overexpressed
      in Escherichia coli as inclusion bodies, solubilized in 6 M guanidine
      hydrochloride, and then refolded in vitro by rapid dilution into a renaturing
      buffer. Refolded B7-2 was subsequently purified to homogeneity by anion-exchange
      chromatography. Gel-filtration chromatography and native PAGE analysis showed
      that the receptor-binding domain of B7-2 is exclusively monomeric in solution.
      Purified B7-2 binds tightly to bacterially expressed monomeric and disulfide
      linked homodimeric human CTLA-4 as shown by gel-filtration chromatography and
      native PAGE. This suggests that glycosylation is not important for the proper
      folding of the receptor-binding domain of B7-2 nor for its binding to CTLA-4. In
      addition, these results suggest that refolded B7-2 is biologically active and may
      be a useful therapeutic and experimental reagent for regulating T cell activity.
      Refolded and purified B7-2 was crystallized by the hanging-drop vapor diffusion
      method, allowing for the initiation of an X-ray crystallographic study.

PMID- 12071706
TI  - Rescue of intracellularly trapped lutropin receptor exodomain by endodomain and
      reconstitution of a functional membrane receptor: interaction between exo- and
      endodomains.
AB  - The lutropin receptor consists of an extracellular N-terminal half and a membrane
      associated C-terminal half. hCG initially binds the exodomain with a high
      affinity and the resulting complex is thought to interact with the endodomain
      through a secondary contact generating a hormonal signal. Therefore, the
      exodomain and endodomain are likely to associate directly or indirectly with each
      other, but lack of fruitful materials and technology has hampered knowledge about
      their physical relationship and contact sites. In this work, we engineered a
      double-recombinant (separate exodomain and endodomain) baculovirus system
      successfully expressing on the surface of insect cells high levels of split LH
      receptor, binding the hormone with high affinity and inducing cAMP synthesis. In
      contrast, the exodomain and endodomain expressed separately were mostly trapped
      in cells. Our data indicate that the exodomain and endodomain are disulfide
      linked in the split receptor. When the disulfide links were reduced, the split
      receptor still induced cAMP up to 60%, which raises the intriguing possibility of
      a residual induction activity of the endodomain in the absence of high-affinity
      ligand binding. Our results also underscore that the targeting and transport of
      the LH receptor to plasma membrane require both domains, whereas each domain is
      independently sufficient for folding. The expression level of functional lutropin
      receptors is the highest ever reported. Our system may also be useful for future
      studies requiring a high amount of soluble secreted exodomain.

PMID- 12071707
TI  - Bacterial expression of a natively folded extracellular domain fusion protein of
      the hFSH receptor in the cytoplasm of Escherichia coli.
AB  - We have expressed the extracellular domain of the hFSH receptor as a fusion
      protein with thioredoxin in the cytoplasm of an Escherichia coli strain that
      contains mutations in both the thioredoxin reductase and the glutathione
      reductase genes. The chimeric protein isolated following induction of expression
      was purified in a soluble form and binds hFSH with an affinity approximating that
      of native receptor. This truncated form of the receptor displays the same
      specificity as intact receptor and does not bind hCG. The protein is expressed at
      levels that exceed 5 mg/L in the bacterial cytoplasm. Expression of the properly
      folded extracellular domain of the hFSH receptor in the cytoplasm of E. coli
      allows the facile and economical purification of large quantities of material.
      This will facilitate the determination of the structure of the hormone-binding
      domain of this glycoprotein receptor as well as the production of epitope
      specific antibodies.

PMID- 12071708
TI  - A rapid selective extraction procedure for the outer membrane protein (OmpF) from
      Escherichia coli.
AB  - Porins are essential pore-forming proteins found in the outer membrane of several
      gram-negative bacteria. Investigating the relationships between molecular
      structure and function involves an extremely time-consuming and labor-intensive
      purification procedure. We report a method for rapid extraction of the outer
      membrane protein, OmpF, from freeze-dried Escherichia coli cells using valeric
      acid, alleviating the effort and time in sample preparation. Extraction results
      in a highly enriched fraction containing OmpF as 76% of the total protein
      content. The apparent molecular mass determined by SDS-PAGE mobility was 38,900,
      similar to that of the monomeric form of OmpF. N-terminal sequencing yielded 23
      amino acids with 100% identity to the published OmpF sequence. The trimeric form
      of OmpF was observed in unheated samples run on SDS-PAGE and analysis of these
      samples by periodic acid/silver staining revealed the presence of unbound
      lipopolysaccharides. Furthermore, this method should prove useful for isolating
      other outer membrane proteins.

PMID- 12071709
TI  - Refolding and purification of recombinant human PDE7A expressed in Escherichia
      coli as inclusion bodies.
AB  - We have investigated the refolding and purification of the catalytic domain of
      human 3',5'-cyclic nucleotide phosphodiesterase 7A1 (PDE7A1) expressed in
      Escherichia coli. A cDNA encoding an N-terminal-truncated PDE7A1(147-482-His) was
      amplified by RT-PCR from human peripheral blood cells and inserted into the
      vector pET21-C for bacterial expression of the enzyme fused to a C-terminal His
      tag. The PDE was found to be expressed in the form of inclusion bodies which
      could be refolded to an active enzyme in buffer containing high concentrations of
      arginine hydrochloride, ethylene glycol, and magnesium chloride at pH 8.5. The
      PDE7A1(147-482-His) construct could be purified after dialysis and concentration
      steps by either Zn2+-IDA-Sepharose chromatography or ResourceQ ion-exchange
      chromatography to homogeneity. In comparison to the metal-chelate column, the
      ResourceQ purification resulted in a distinctly better yield and enrichment of
      the protein. Both the Vmax (0.46 micromol. min(-1). mg(-1) ) and the K(m) (0.1
      microM) of the purified enzyme were found to be comparable with published data
      for native or recombinant catalytically active expressed PDE7A1. Using SDS/PAGE,
      a molecular mass of 39 kDa was determined (theoretical value 38.783 kDa). As
      known from several other mammalian PDEs, size-exclusion chromatography using
      refolded PDE7A1(147-482-His) indicated the formation of dimers. The purified
      enzyme was soluble at concentrations up to 100 microg/ml. A further increase of
      protein concentration resulted, however, in precipitation of the enzyme.

PMID- 12071710
TI  - Purification and biochemical characterization of the ErmSF macrolide-lincosamide
      streptogramin B resistance factor protein expressed as a hexahistidine-tagged
      protein in Escherichia coli.
AB  - The erm proteins confer resistance to the MLS (macrolide-lincosamide
      streptogramin B) antibiotics in various microorganisms, including pathogens,
      through dimethylation of a single adenine residue (A2085: Bacillus subtilis
      coordinate) of the 23S rRNA to reduce the affinity of antibiotics, thereby
      enabling the cells to escape from the antibiotics' action, and this mechanism is
      predominantly adopted by microorganisms resistant to MLS antibiotics. ErmSF
      methyltransferase is one of the four gene products synthesized by Streptomyces
      fradiae NRRL 2338 to be resistant to its autogenous antibiotic, tylosin. In order
      to have a convenient source for the purification of milligram amounts, we
      expressed ErmSF in Escherichia coli using a T7 promoter-driven expression vector
      system, pET 23b, and the protein was expressed with a carboxy-terminal addition
      of six histidine residues in order to facilitate purification. Expression at 22
      degrees C reduced the formation of insoluble aggregate, inclusion body, and
      resulted in accumulation of soluble hexahistidine-ErmSF up to 30% of total cell
      protein after 18 h. Metal-chelation chromatography yielded 126 mg of
      hexahistidine-ErmSF per liter of culture with a purity slightly greater than 95%.
      To examine the function of ErmSF in vivo and in vitro, its activity in E. coli
      (antibiotic susceptibility assay) andin vitro methyltransferase activity using in
      vitro-produced B. subtilis domain V, 434-, 257-, and 243-nt RNAs were
      investigated. The ErmSF in E. coli conferred resistance to erythromycin, whereas
      E. coli harboring an empty vector, pET23b, was susceptible. The purified
      recombinant protein successfully methylated domain V of 23S rRNA, which is known
      to contain all of the substrate elements recognized and to be methylated by erm
      proteins. However, the truncated substrates were methylated with decreased
      efficiencies. Almost all of domain V was monomethylated with less than 0.2 pM S
      [methyl-(3)H]adenosylmethionine concentration. The roles of three structurally
      divided regions of domain V in recognition and methylation by ErmSF are proposed
      through kinetic studies using RNA substrates, in which each region is deleted,
      under the monomethylation condition.

PMID- 12071711
TI  - Expression and production of recombinant human interleukin-2 in potato plants.
AB  - Interleukin-2 is a pharmacologically important cytokine secreted by T
      lymphocytes. Recombinant interleukin-2 has been produced and found to be useful
      for many medical applications. Mass production of recombinant interleukin-2 will
      be prerequisite for a wider application of this molecule. In this study we
      investigated the possibility of using potato tubers for the production of
      recombinant human interleukin-2 in large quantity. A binary vector carrying the
      human interleukin-2 gene under a potato tuber-specific promoter (patatin
      promoter) was constructed. Several potato transformants expressing the human
      interleukin-2 gene were generated by Agrobacterium-mediated transformation.
      Expression of the human interleukin-2 gene was confirmed by Northern blotting and
      the protein level was determined by Western blot analyses. A bioassay revealed
      that human interleukin-2 expressed in the potato tuber supported proliferation of
      interleukin-2-dependent cells, CTLL-2. We found that the recombinant protein in
      the 2-week-old microtuber has the highest activity (115 units per gram of
      microtuber) and estimated that an average yield for a potato (average 200 g per
      potato) was 23,000 units of rhIL-2 activity. The results suggest that the potato
      tuber is an excellent system for the mass production of biologically active human
      interleukin-2.

PMID- 12071712
TI  - Bacterial expression and in vitro refolding of a single-chain fv antibody
      specific for human plasma apolipoprotein B-100.
AB  - From the cloned heavy and light chains of a murine monoclonal antibody (mAbB23)
      which is specific for human apolipoprotein (apo) B-100 of plasma low-density
      lipoproteins, a vector was designed for expression of a single-chain antibody
      (scFv) of mAbB23 in Escherichia coli. The expression vector was constructed so
      that the scFv gene (V(L)-linker-V(H)) was expressed under the control of the T7
      promoter. The inclusion body of scFv was isolated from E. coli lysate and
      solubilized in 6 M guanidine-hydrochloride without reducing agents, followed by
      refolding through slow dilution into refolding buffer. After complete removal of
      the remaining denaturant by dialysis, the soluble scFv was purified through an
      apo B-100-coupled affinity column, and an active fraction, which had an antigen
      binding activity comparable with that of native Fab, was easily obtained. The
      expression and in vitro refolding of scFv resulted in production of an active
      molecule in a yield of 15-20 mg per 1-liter flask cultivation.

PMID- 12071713
TI  - Chromatographic methods for the isolation of, and refolding of proteins from,
      Escherichia coli inclusion bodies.
AB  - New methods for the chromatographic isolation of inclusion bodies directly from
      crude Escherichia coli homogenates and for the refolding of denatured protein are
      presented. The traditional method of differential centrifugation for the
      isolation of purified inclusion bodies is replaced by a single gel-filtration
      step. The principle is that the exclusion limit of the gel particles is chosen
      such that only the inclusion bodies are excluded, i.e., all other components of
      the crude homogenate penetrate the gel under the conditions selected. In the
      novel column refolding process, a decreasing gradient of denaturant (urea or Gu
      HCl), combined with an increasing pH gradient, is introduced into a gel
      filtration column packed with a gel medium that has an exclusion limit lower than
      the molecular mass of the protein to be refolded. A limited sample volume of the
      protein, dissolved in the highest denaturant concentration at the lowest pH of
      the selected gradient combination, is applied to the column. During the course of
      elution, the zone of denatured protein moves down the column at a speed
      approximately threefold higher than that of the denaturant. This means that the
      protein sample will gradually pass through areas of increasingly lower denaturant
      concentrations and higher pH, which promotes refolding into the native
      conformation. The shape and slope of the gradients, as well as the flow rate,
      will influence the refolding rate and can be adjusted for different protein
      samples. The principle is illustrated using a denatured recombinant scFv fusion
      protein obtained from E. coli inclusion bodies.

PMID- 12071714
TI  - The interaction of recombinant decorin with alpha2HS-glycoprotein-implications
      for structural and functional investigations.
AB  - Isolated protein preparations of the small leucine-rich proteoglycans (SLRPs)
      associated with mineralized tissues have provided important information in
      understanding their structural and functional interactions within extracellular
      matrices and their potential roles in mineralization. Two important SLRPs,
      decorin and biglycan, copurify following extraction and purification from
      mineralized tissues using standard procedures, and to overcome this problem
      decorin was synthesized within a mammalian expression system to obtain pure
      preparations. The expressed protein was purified from the culture medium using
      anion-exchange chromatography, and characterization confirmed the presence of a
      decorin-rich fraction. However, N-terminal sequencing revealed the additional
      presence of alpha2HS-glycoprotein (alpha2HSG), representing approximately 35% of
      the total purified fraction. The decorin-rich fraction was subjected to selected
      further purification techniques to separate decorin from alpha2HSG. Application
      of the sample at a low concentration (1 mg/ml) to a second anion-exchange
      procedure and elution over an expanded sodium chloride gradient resulted in a
      high degree of purity (98%), with a single protein isolate demonstrable by SDS
      PAGE. Electroelution achieved partial purification ( approximately 89%), but
      immunoprecipitation with antibodies against the glycosaminoglycan chain and the
      polyhistidine tag failed to separate the two proteins. This study suggests there
      is a strong interaction between recombinantly produced decorin and alpha2 HSG and
      highlights the importance of the purification technique to the application of
      recombinantly produced proteins or those that have been extracted from
      mineralized tissues for use in structural and functional interactions.

PMID- 12071715
TI  - Expression and purification of aspartate beta-semialdehyde dehydrogenase from
      infectious microorganisms.
AB  - l-Aspartate-beta-semialdehyde dehydrogenase (ASA DH) lies at the first branch
      point in the aspartate metabolic pathway that leads to the formation of the amino
      acids lysine, isoleucine, methionine, and threonine in most plants, bacteria, and
      fungi. Since the aspartate pathway is not found in humans, but is necessary for
      bacterial cell wall biosynthesis, the enzymes in this pathway are potential
      targets for the development of new antibiotics. The asd gene that encodes for ASA
      DH has been obtained from several infectious organisms and ligated into a pET
      expression vector. ASA DHs from Haemophilus influenza, Pseudomonas aeruginosa,
      and Vibrio cholerae were expressed as soluble proteins in Escherichia coli, while
      ASA DH from Helicobacter pylori was obtained primarily as inclusion bodies. The
      V. cholerae genome contains two asd genes. Both enzymes have been expressed and
      purified, and each displays significant ASA DH activity. The purification of
      highly active ASA DH from each of these organisms has been achieved for the first
      time, in greater than 95% purity and high overall yield. Kinetic parameters have
      been determined for each purified enzyme, and the values have been compared to
      those of E. coli ASA DH.

PMID- 12071716
TI  - Expression and affinity purification of recombinant proteins from plants.
AB  - With recent advances in plant biotechnology, transgenic plants have been targeted
      as an inexpensive means for the mass production of proteins for biopharmaceutical
      and industrial uses. However, the current plant purification techniques lack a
      generally applicable, economic, large-scale strategy. In this study, we
      demonstrate the purification of a model protein, beta-glucuronidase (GUS), by
      employing the protein calmodulin (CaM) as an affinity tag. In the proposed
      system, CaM is fused to GUS. In the presence of calcium, the calmodulin fusion
      protein binds specifically to a phenothiazine-modified surface of an affinity
      column. When calcium is removed with a complexing agent, e.g., EDTA, calmodulin
      undergoes a conformational change allowing the dissociation of the calmodulin
      phenothiazine complex and, therefore, permitting the elution of the GUS-CaM
      fusion protein. The advantages of this approach are the fast, efficient, and
      economical isolation of the target protein under mild elution conditions, thus
      preserving the activity of the target protein. Two types of transformation
      methods were used in this study, namely, the Agrobacterium-mediated system and
      the viral-vector-mediated transformation system.

PMID- 12071717
TI  - Cloning, overexpression, purification, and matrix-assisted refolding of DevS (Rv
      3132c) histidine protein kinase of Mycobacterium tuberculosis.
AB  - The devR-devS (Rv 3133c-Rv 3132c) two-component system of Mycobacterium
      tuberculosis was identified in our laboratory by RNA subtractive hybridization.
      This genetic system was predicted to encode a response regulator and histidine
      protein kinase, respectively. The putative histidine kinase protein DevS was
      overexpressed to high levels in Escherichia coli as a fusion protein with a
      hexahistidine tag, His(6)-DevS201, in the form of inclusion bodies. Here we
      report a "redox-based" method of matrix-bound renaturation of DevS protein. The
      refolded protein was biochemically active in an autophosphorylation reaction
      characteristic of histidine kinases and was suitable for the generation of
      polyclonal antibodies and as an antigen in ELISA.

PMID- 12071718
TI  - A smart adhesive joint: entropic control of adhesion at a polymer/metal
      interface.
AB  - The study of adhesion has a long and rich history, with theory, experiments, and
      applications bridging numerous disciplines, including physics, chemistry,
      engineering, and medicine. This diverse interest has led to the development of a
      large number of methods for both enhancing and inhibiting adhesion at specific
      interfaces of interest. We report herein "smart" adhesion at a polymer/metal
      (oxide) interface that responds reversibly to changes in temperature by
      increasing or decreasing in magnitude. The temperature dependence in this system
      arises from the rubber elasticity of the polymer, 1,4-polybutadiene, and mirrors
      the interfacial behavior of the same polymer against water. Such systems offer
      unique opportunities for designing responsive materials whose properties can be
      actively controlled.

PMID- 12071719
TI  - Synthesis of novel quaternary amino acids using molybdenum-catalyzed asymmetric
      allylic alkylation.
AB  - The Mo-catalyzed asymmetric allylic alkylation using azlactones provides
      extraordinary levels of selectivity. Thus, a wide range of cinnamyl-type
      substrates react with 2-methyl and 2-benzyl azlactones to give only the product
      resulting from attack at the more substituted carbon. Using other alkyl
      substituents such as 2-methylthioethyl, isobutyl, allyl, and isopropyl provides
      products that still retain excellent regioselectivity but small quantities of the
      linear product are also observed. In all cases, excellent diastereo- and
      enantioselectivity of the branched alkylated product are observed. This new
      asymmetric reaction provides ready access to unusual quarternary amino acids,
      important building blocks for biological applications. The reactions complements
      the Pd AAA wherein the cinnamyl substrate leads to only the product of attack at
      the primary terminus of the allyl moiety.

PMID- 12071720
TI  - Design and synthesis of biotin chain-terminated glycopolymers for surface
      glycoengineering.
AB  - Biotin chain-terminated glycopolymers were generated by cyanoxyl-mediated free
      radical polymerization using a biotin-derivatized arylamine initiator with high
      conversion (75%) and low polydispersity (1.30). Streptavidin-biotinylated
      glycopolymer binding was verified by SDS-PAGE gel shift assay and patterned
      glycocalyx-mimetic surfaces successfully fabricated.

PMID- 12071721
TI  - Characterization and reactions of previously elusive 17-electron cations:
      electrochemical oxidations of (C(6)H(6))Cr(CO)(3) and (C(5)H(5))Co(CO)(2) in the
      presence of [B(C(6)F(5))(4)](-).
AB  - The electrochemical oxidations of (C6H6)Cr(CO)3, 1, and (C5H5)Co(CO)2, 2, when
      carried out in CH2Cl2/[NBu4][B(C6F5)4], allow the physical or chemical
      characterization of the 17-electron cations 1+ and 2+ at room temperature. The
      generation of 1+ on a synthetic time scale permits an electrochemical "switch"
      process involving facile substitution of CO by PPh3 as a route to
      (C6H6)Cr(CO)2PPh3. The radical 2+ undergoes a second-order reaction to give a
      product assigned as the metal-metal bonded dimer dication [Cp2Co2(CO)4]2+. The
      new anodic chemistry of these often-studied 18-electron compounds is made
      possible by increases in the solubility and thermal stability of the cation
      radicals in media containing the poorly nucleophilic anion [B(C6F5)4]-, TFAB.

PMID- 12071722
TI  - Use of medium effects to tune the Delta E(1/2) values of bimetallic and
      oligometallic compounds.
AB  - The redox potentials of bis(fulvalene)dinickel, 1, and the
      tetrakis(ferrocenyl)nickel dithiolene complex 2 have been measured in a variety
      of nonaqueous electrolytes. The difference in E1/2 values of the two successive
      one-electron oxidations of 1 (i.e., DeltaE1/2 values) increased from a low of 212
      mV in anisole/[NBu4]Cl to a high of 850 mV in CH2Cl2-Na[B(C6H3(CF3)2)4],
      reflecting an increase of over 1010 in the comproportionation constant (Kcomp =
      [1+]2/[1][12+]). Six reversible one-electron processes are possible for compound
      2, the four oxidations arising from the ferrocenyl substituents, and the two
      reductions arising from the Ni dithiolene moiety. The E1/2 spreads of the four
      oxidation waves and the two reduction waves are both highly sensitive to medium
      effects. For both 1 and 2, the largest DeltaE1/2 values for cationic products are
      found in solvents of low polarity and donor strength containing electrolyte salts
      having large anions and small cations. Conversely, the smallest DeltaE1/2 values
      for anionic products are found under these conditions, culminating in the
      observation of a single two-electron reduction wave for 2/22- in CH2Cl2
      Na[B(C6H3(CF3)2)4]. A combination of solvation and ion-pairing effects must be
      considered, and may be used to advantage, when using DeltaE1/2 values as a
      measure of electronic interactions between redox centers in compounds containing
      two or more electron-transfer sites.

PMID- 12071723
TI  - Observation of azo chromophore fluorescence and phosphorescence emissions from
      DBH by applying exclusively the orbital confinement effect in siliceous zeolites
      devoid of charge-balancing cations.
AB  - The molecular orbital (MO) confinement theory predicts that the HOMO and LUMO of
      an organic guest may become distorted when the dimensions of the host cavity
      approach closely those of the MO (Corma, A.; Garcia, H.; Sastre, G.; Viruela, P.
      M. J. Phys. Chem. B 1997, 101, 4575-4582). Generally, quantum chemical
      calculations assume that the MO extends over all the space. However, the fact
      that a molecule is confined within a restricted cavity might impose certain
      limits to its MO. In agreement with this theory, we have observed for the first
      time the phosphorescence emission from 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH)
      upon incorporation in zeolites devoid of charge-balancing cations, even at room
      temperature. This observation may be rationalized on the basis of two possible
      effects: (i) Decrease of the HOMO-LUMO gap induced by confinement of the azo np*
      chromophore favors ISC, and (ii) inhibition of radiationless deactivation pathway
      by the immobilization of DBH within the zeolite host favors long lifetimes.

PMID- 12071725
TI  - Quantum dynamics of hydride transfer catalyzed by bimetallic electrophilic
      catalysis: synchronous motion of Mg(2+) and H(-) in xylose isomerase.
AB  - Xylose isomerase exhibits a bridged-bimetallic active-site motif in which the
      substrate is bound to two metals connected by a glutamate bridge, and X-ray
      crystallographic studies suggest that metal movement is involved in the hydride
      transfer rate-controlling catalytic step. Here we report classical/quantal
      dynamical simulations of this step that provide new insight into the metal
      motion. The potential energy surface is calculated by treating xylose with
      semiempirical molecular orbital theory augmented by a simple valence bond
      potential and the rest of the system by molecular mechanics. The rate constant
      for the hydride-transfer step was calculated by ensemble-averaged dynamical
      simulations including both variational transition-state theory for determination
      of the statistically averaged dynamical bottleneck and optimized multidimensional
      tunneling calculations. The dynamics calculations include 25 317 atoms, with
      quantized vibrational free energy in 89 active-site degrees of freedom, and with
      32 atoms moving through static secondary zone transition-state configurations in
      the quantum tunneling simulation. Our simulations show that the average Mg-Mg
      distance R increases monotonically as a function of the hydride-transfer progress
      variable z. The range of the average R along the reaction path is consistent with
      the X-ray structure, thus providing a dynamical demonstration of the postulated
      role of Mg in catalysis. We also predicted the primary deuterium kinetic isotope
      effect (KIE) for the chemical step. We calculated a KIE of 3.8 for xylose at 298
      K, which is consistent with somewhat smaller experimentally observed KIEs for
      glucose substrate at higher temperatures. More than half of our KIE is due to
      tunneling; neglecting quantum effects on the reaction coordinate reduces the
      calculated KIE to 1.8.

PMID- 12071724
TI  - Coordination-driven self-assembly: solids with bidirectional porosity.
AB  - Coordination-driven self-assembly reactions have been used in the preparation of
      a variety of discrete supramolecular species, some of which have shown promise as
      synthetic receptors. Many highly ordered coordination polymers and porous
      networks have been prepared in a similar fashion. While a few of these solids are
      capable of the uptake of small organic molecules in the resultant molecular
      channels, the formation of truly porous structures has frequently been thwarted
      by lattice interpenetration. A strategy for the formation of porous solids that
      may circumvent this problem is based on the covalent construction of nanoscale
      macrocycles which, when eclipsed in the solid state, may lead to porous, tubular
      assemblies. We have incorporated these concepts toward the realization of a
      bidirectionally porous solid. The metal-directed, self-assembly of a conjugated,
      macrocyclic ligand provides a discrete, supramolecular entity in solution and the
      solid state. X-ray crystallographic analysis establishes that this assembly packs
      such that bidirectional channels are realized, and the incorporation of only
      ClCH2CH2Cl into the crystal lattice demonstrates that these channels are
      potentially suitable for the selective uptake of small organic guests.

PMID- 12071726
TI  - Trehalose glass-facilitated thermal reduction of metmyoglobin and methemoglobin.
AB  - The reduction of ferric derivatives of hemeproteins in solution typically
      requires moderate to strong reducing agents. Reducing sugars are not adequate to
      reduce ferric myoglobins or hemoglobins under solution conditions favorable to
      protein stability. We find that embedding aquo-met derivatives of horse myoglobin
      and human adult hemoglobin in a glucose-doped glassy matrix derived from
      trehalose facilitates an efficient thermally initiated reduction that yields a
      five-coordinate high-spin ferrous heme. The trehalose glass plays a central role
      by stabilizing the reduction-prone bis-histidine heme (hemichrome) intermediate
      under the high-temperature conditions that favor the open reducing form of
      glucose. Due to glass-imposed limitations on conformational reorganization, this
      process has clear applications in biophysics where it can be used to generate
      nonequilibrium ferrous derivatives having the initial conformation of the aquo
      met derivative. Since the glassy matrix can be redissolved to release the
      embedded protein, this technique is not only a basis for a relatively benign
      method of reducing hemoglobin-based blood substitutes that have undergone
      autoxidation during storage but may also be a way to reactivate stored proteins
      that have undergone oxidation.

PMID- 12071727
TI  - Base flipping in DNA: pathways and energetics studied with molecular dynamic
      simulations.
AB  - Carrying out chemistry on the bases of DNA, necessary for biological processes
      such as methylation or repair, requires flipping the base into an accessible
      position. In this work, molecular dynamics simulations are used to generate a
      free energy profile for flipping a cytosine base out of its helical stack in
      double-stranded DNA. The results shed light on the mechanics of this process by
      comparing routes for base flipping via the minor and major grooves.

PMID- 12071728
TI  - Sugar acetates as novel, renewable CO(2)-philes.
AB  - Acetylation of carbohydrates is proposed as a method for the synthesis of
      inexpensive CO2-philes that can easily be modified for a wide variety of green
      chemistry applications in liquid and supercritical CO2. The deliquescence of
      peracetylated sugars in contact with CO2 is reported in this communication as
      well as the unparalleled solubility of these compounds in supercritical CO2.

PMID- 12071729
TI  - Exceptional kinetic propensity of hydroxymethyl phosphanes toward Rh(III)
      stabilization in water.
AB  - The reactions of (HOCH2)2P(C6H4)P(CH2OH)2 (HMPB) and P(CH2OH)3 (THP) with
      RhCl3.xH2O in aqueous media gave water-soluble complexes cis-[RhCl2{eta2
      (HOCH2)2P(C6H4)P(CH2OH)2}2]Cl (3) and fac-[RhCl3(P(CH2OH)3)3] (4) respectively in
      good yields, X-ray crystal structures of 3 and 4 confirmed their molecular
      constitution. These reactions provide the first examples demonstrating the
      kinetic propensity of hydroxymethyl phosphanes to stabilize Rh in +3 oxidation
      state in water.

PMID- 12071730
TI  - Fapy.dG instructs Klenow exo(-) to misincorporate deoxyadenosine.
AB  - The effects of Fapy.dG (N-(2-deoxy-alpha,beta-d-erythropentofuranosyl)-N-(2,6
      diamino-4-hydroxy-5-formamidopyrimidine)) on the activity of Klenow exo- have
      been determined by using oligonucleotide substrates containing the lesion at a
      defined site. Fapy.dG inhibits primer polymerization at two positions: nucleotide
      incorporation opposite the lesion and extension one nucleotide past the lesion.
      Klenow exo- is inhibited less by Fapy.dG than by its analogue, MeFapy.dG. Fapy.dG
      instructs the polymerase to misincorporate deoxyadenosine opposite itself 20
      times more frequently than does dG. Extension of the primer containing the
      Fapy.dG:dA base pair is only slightly less efficient than when dC is opposite the
      lesion. Overall, Fapy.dG increases the probability that Klenow exo- will make a
      mistake during replication approximately 80-million fold compared to a template
      containing the native nucleotide, dG.

PMID- 12071731
TI  - Infrared spectrum of the novel electron-deficient BH(4) radical in solid neon.
AB  - Laser-ablated boron reacts with hydrogen on condensation in excess neon to give
      BH4 radical, BH4- anion, and B2H6 as the major products. Identifications are
      based on 10B and D substitution, DFT frequency calculations, and comparison to
      previous spectra. Infrared spectra of BH4 support the C2v structure deduced from
      previous ESR spectra and theoretical calculations with two normal B-H bonds and
      two long B-H bonds for this novel electron-deficient radical. NBO analysis
      suggests that the two long B-H bonds and the H- -H bond are one-electron bonds.

PMID- 12071732
TI  - Living alternating copolymerization of N-alkylaziridines and carbon monoxide as a
      route for synthesis of poly-beta-peptoids.
AB  - The title copolymerization catalyzed by BnCOCo(CO)4 affords poly-beta-alanoids in
      excellent yields and selectivity. The poly-beta-alanoids have narrow molecular
      weight distributions, controllable molecular weights, and definite end groups.

PMID- 12071733
TI  - Conformation and absolute configuration of nocathiacin I determined by NMR
      spectroscopy and chiral capillary electrophoresis.
AB  - Nocathiacin I (BMS-249524) is a highly cross-linked thiazolyl peptide that
      displays potent activity against Gram-positive bacteria, including a number of
      antibiotic-resistant strains. This natural product contains 10 chiral centers.
      NMR studies have been performed to characterize the solution structure of
      nocathiacin I. A uniformly 13C,15N-labeled sample was used to obtain NMR
      assignments. Restrained simulated annealing calculations were performed by using
      accurately determined NOE distance restraints. All of the chiral centers were
      allowed to float during the simulated annealing protocol. Two clusters of
      structures were obtained that satisfy the NOE restraints very well and that are
      reasonably consistent with vicinal J-coupling constants. Within each cluster, all
      10 chiral centers are uniquely defined. The two clusters are effectively mirror
      images of each other: all chiral centers that have the R(S) configuration in one
      cluster have the S(R) configuration in the other. The single threonine residue in
      nocathiacin I was subsequently determined to be l-threonine by chiral capillary
      electrophoresis, allowing the absolute configurations of all 10 chiral centers to
      be defined.

PMID- 12071734
TI  - Rational design to block amino acid editing of a tRNA synthetase.
AB  - Investigations in chemical biology have focused on the synthesis of custom
      designed proteins with site-specific incorporation of novel amino acids. Their
      success requires stable production of misacylated tRNAs. Utilization of aminoacyl
      tRNA synthetases has been hindered because of enzyme molecular recognition
      mechanisms that ensure high fidelity of protein synthesis. Leucyl-tRNA synthetase
      naturally misaminoacylates chemically diverse standard and nonstandard amino
      acids, but contains a separate amino acid editing active site to hydrolyze
      incorrectly mischarged tRNAs. In this work, a rational mutagenesis design to
      block enzyme editing is described and involves substitution of bulky amino acids
      into the amino acid binding pocket of the hydrolytic active site. These
      engineered enzymes stably misacylated isoleucine to tRNALeu. The use of these
      mutant leucyl-tRNA synthetases has the potential to produce pools of mischarged
      tRNAs that are linked to nonstandard amino acids for in vitro translation. In
      addition, since many of the leucyl-tRNA synthetases do not interact with or rely
      upon the tRNA anticodon for identity, these enzymes may offer an excellent
      scaffold for the development of orthogonal tRNA synthetase/tRNA pairs that can
      potentially be used to customize protein synthesis.

PMID- 12071735
TI  - Connectivity of features in microlens array reduction photolithography:
      generation of various patterns with a single photomask.
AB  - Microlens array photolithography (MAP) is a technique in which arrays of
      microlenses positioned close to photoresist reduce cm-sized figures on photomasks
      and form mum-scale images in the photoresist. This work demonstrates that MAP,
      using a single photomask, can generate patterns having different symmetries and
      periodicities from that of the lens array. This capability of MAP depends on (i)
      the connectivity between the images produced by individual microlenses and (ii)
      the orientation of the photomask relative to the lens array prior to exposure. By
      changing this orientation, MAP, using a single mask and a single array of
      microlenses, could be used to generate patterns that (i) are separated from each
      other, (ii) overlap with each other, (iii) are 2D chiral, and thus different from
      both the lens array and the mask in symmetry, (iv) have a symmetry reduced from
      that of the lens array, or (v) have a smaller unit cell and smaller pitch than
      that of the lens array.

PMID- 12071736
TI  - Correlated electrons in the Eu-exchanged Preyssler anion [EuP(5)W(30)O(110)](n-).
AB  - The Eu-encrypted Preyssler anion, [EuP5W30O110]n-, demonstrates unusual
      electronic properties as a function of applied potenial. The Preyssler anion
      itself, when exchanged with a nonredox active trivalent ion such as La3+, is
      electroactive in acidic solution, reversibly accepting up to 10 electrons under
      reducing conditions. Encrypted Eu, which is trivalent at rest potential, is
      reduced concomitantly with the framework. The details of this reduction are
      probed with Eu L3-XANES, coulometry, and magnetic susceptibility. The results are
      interpreted in terms of a bonding interaction between the Eu f-states and the W-O
      framework band, facilitated by the crossing of the framework Fermi level with the
      localized states. Such behavior has been previously observed in intermediate
      valent and correlated-electron systems. The observation of such behavior in an
      isolated cluster opens the door for new avenues of research into correlated
      electron behavior.

PMID- 12071737
TI  - A new synthetic route to boron-10 enriched pentaborane(9) from boric acid and its
      conversion to anti-(10)B(18)H(22).
AB  - Boron-10 enriched boric acid, H310BO3, was converted to the corresponding sodium
      borohydride, Na10BH4, in essentially quantitative yields, by using slightly
      modified literature methods involving the formation of butyl borate, (n-OBu)310B,
      first and then reacting it with NaH in mineral oil. The oxidation reaction of
      Na10BH4 with I2 in diglyme and subsequent addition/purification in dioxane gave
      Na[10B3H8]0.3(C4H8O2) that reacted further with NiCl2 in either anhydrous benzene
      or heavy mineral oil at 110 degrees C to produce the corresponding 10B5H9 as the
      first isolated 10B-enriched liquid boron hydride in a laboratory environment.
      Treatment of this 10B5H9 with NaH or t-BuLi in 2:1 molar ratio underwent a cage
      expansion reaction to produce the [M]10B9H14 that undergoes a redox reaction in
      situ with anhydrous NiCl2 in n-hexane to yield the corresponding fused cage anti
      10B18H22 as the only solid borane product in 42% yield, thus establishing new
      synthetic routes for the preparation of 10B-enriched polyhedral boranes.

PMID- 12071738
TI  - Solution and biologically relevant conformations of enantiomeric 11-cis-locked
      cyclopropyl retinals.
AB  - To gain information on the conformation of the 11-cis-retinylidene chromophore
      bound to bovine opsin, the enantiomeric pair (2a and 2b) of 11-cis-locked
      bicyclo[5.1.0]octyl retinal (retCPr) 2 was prepared and its conformation was
      investigated by NMR, geometry optimization, and CD calculations. This compound is
      also of interest since it contains a unique moiety in which a chiral cyclopropyl
      group is flanked by triene and enal chromophores, and hence would clarify the
      little-known chiroptical contribution of a cyclopropyl ring linked to polyene
      systems. NMR revealed that the seven-membered ring of retCPr adopts a twist chair
      conformation. The NMR-derived structure constraints were then used for optimizing
      the geometry of 2 with molecular mechanics and ab initio methods. This revealed
      that enantiomer 2a with a 11 beta,12 beta-cyclopropyl group exists as two
      populations of diastereomers depending on the twist around the 6-s bond; however,
      the sense of twist around the 12-s is positive in both rotamers. The theoretical
      Boltzmann-weighted CD obtained with the pi-SCF-CI-DV MO method and experimental
      spectra were consistent, thus suggesting that the conjugative effect of the
      cyclopropyl moiety is minimal. It was found that only the beta-cyclopropyl
      enantiomer 2a, but not the alpha-enantiomer 2b, binds to opsin. This observation,
      together with earlier retinal analogues incorporation results, led to the
      conclusion that the chromophore sinks into the N-terminal of the opsin receptor
      from the side of the 4-methylene and 15-aldehyde, and that the binding cleft
      accommodates 11-cis-retinal with a slightly positive twist around C12/C13. A
      reinterpretation of the previously published negative CD couplet of 11,12
      dihydrorhodopsin also leads to a chromophoric C12/C13 twist conformation with the
      13-Me in front as in 1b. Such a conformation for the chromophore accounts for
      both the observed biostereoselectivity of retCPr 2a and the observed negative
      couplet of 11,12-dihydro-Rh7.

PMID- 12071739
TI  - The mechanism of cis-trans isomerization of prolyl peptides by cyclophilin.
AB  - The mechanism of cis-trans isomerization of prolyl peptides catalyzed by
      cyclophilin (CyP) was studied computationally via molecular dynamics (MD)
      simulations of the transition state (TS) and the cis and trans forms of the
      ground state (GS), when bound to CyP and when free in aqueous solution. The MD
      simulations include four enzyme-bound species of tetrapeptide (Suc-Ala-XC([double
      bond]O)-NPro-Phe-pNA; X = Gly, Trp, Ala, and Leu). In water, the prolyl amide
      bond is favorably planar with the presence of conformers exhibiting +/-20 degrees
      twist of the C-N dihedral. In the active site a hydrogen bond between the cis
      prolyl amide carbonyl O and the backbone amide N-H of Asn102 retains the 20
      degrees twist of the C-N dihedral. The TS structure is characterized by a 90
      degrees twist of the amide C-N bond and a more favorable interaction with Asn102
      due to the shorter distance between Asn102(HN) and the amide carbonyl O. The
      conformational change of cis --> TS also involves pyramidalization of the amide
      N, which results in the formation of a hydrogen bond between the amide N and the
      guanidino group of Arg55. Both Asn102 and Arg55 are held in the same position in
      CyP.cis-isomer as in CyP.TS. In the ligand-free CyP the Arg55 guanidino group is
      highly disorganized and Asn102 is displaced 1 A from the position in the ligand
      bound CyP. Thus, the organization of Arg55 and Asn102 occurs upon substrate
      binding. The geometrical complimentarity of the organized enzyme structure to the
      TS structure is a result of preferential binding of the proline N and the amide
      carbonyl of the TS compared to that of GS. However, the N-terminal part (Suc-Ala)
      becomes repositioned in the TS such that two hydrogen bonds disappear, one
      hydrogen bond appears and two other hydrogen bonds becomes weaker on the
      conversion of CyP.cis to CyP.TS. During this conversion, total hydrophobic
      contact between enzyme and the peptide is preserved. Thus, the interaction
      energies of GS and TS with enzyme are, as a whole, much alike. This does not
      support the contention that TS is bound more tightly than GS by K(m)/K(TS) =
      10(6) in the cis --> trans reaction. Repositioning of the N-terminal part of the
      peptide on CyP.TS formation becomes more pronounced when the substrate X residue
      is changed from Gly < Trp < Ala < Leu. We propose that the larger turning of the
      N-terminus is responsible for the larger value of the experimentally observed
      Delta S(++) and Delta H(++), which sum up to little change in Delta G(++). The
      positioning of the Arg55 and the degree of 20 degrees twist of the amide C-N bond
      are considered as criteria for Near Attack Conformers (NACs) in cis-trans
      isomerization. NACs account for approximately 30% of the total GS populations of
      the cis-isomer. Similar NAC populations were observed with four different
      substrates. This is consistent with the insensitivity of enzymatic activity to
      the nature of the X residue. Also, the NAC population in CyP.trans-AAPF was
      comparable to that in CyP.cis-AAPF, in accord with similar experimentally
      measured rates of the cis --> trans and trans --> cis reaction in CyP. These
      NACs, found in CyP.cis and CyP.trans, resemble only one of the four possible TS
      configurations in the water reaction. The identity of this TS structure (syn/exo)
      is in accord with experimentally determined KIE values in the enzymatic reaction.
      However, the geometry of the active site was also complementary to another TS
      structure (anti/exo) that was not detected in the active site by the same KIE
      measurements, implying that the geometrical fitness of the TS cannot be a single
      determining factor for enzymatic reactions.

PMID- 12071740
TI  - Hybridization and enzymatic extension of au nanoparticle-bound oligonucleotides.
AB  - We have investigated the impact of steric effects on the hybridization and
      enzymatic extension of oligonucleotides bound to 12-nm colloidal Au particles. In
      these experiments, a nanoparticle-bound 12-mer sequence is hybridized either to
      its solution phase 12-mer complement or to an 88-mer template sequence. The
      particle-bound oligonucleotide serves as a primer for enzymatic extension
      reactions, in which covalent incorporation of nucleotides to form the complement
      of the template is achieved by the action of DNA polymerase. Primers were
      attached via-C(6)H(12)SH, -C(12)H(24)SH, and -TTACAATC(6)H(12)SH linkers attached
      at the 5' end. Primer coverage on the nanoparticles was varied by dilution with
      (5')HSC(6)H(12)AAA AAA(3'). Hybridization efficiencies were determined as a
      function of linker length, primer coverage, complement length (12-mer vs 88-mer),
      and primer:complement concentration ratio. In all cases, hybridization for the 88
      mer was less efficient than for the 12-mer. Low primer surface coverage, greater
      particle-primer separation, and higher primer:complement ratios led to optimal
      hybridization. Hybridization efficiencies as high as 98% and 75% were observed
      for the 12-mer and 88-mer, respectively. Enzymatic extension of particle-bound
      primers was observed under all conditions tested; however, the efficiency of the
      reaction was strongly affected by linker length and primer coverage. Extension of
      primers attached by the longest linker was as efficient as the solution-phase
      reaction.

PMID- 12071741
TI  - Mimicry of host-defense peptides by unnatural oligomers: antimicrobial beta
      peptides.
AB  - We have designed beta-amino acid oligomers that are helical, cationic, and
      amphiphilic with the intention of mimicking the biological activity of
      amphiphilic, cationic alpha-helical antimicrobial peptides found in nature (e.g.,
      magainins). We have previously identified a 17-residue beta-peptide (called beta
      17) with antibiotic activity similar to that of a magainin derivative against
      four bacterial species, including two clinical isolates that are resistant to
      common antibiotics. This beta-peptide displays very low hemolytic activity
      against human red blood cells, which indicates selectivity for bacterial cells
      over mammalian cells. Here we examine some of the factors important for activity
      in this class of beta-peptides. An amphiphilic helix is necessary, because a
      nonamphiphilic isomer proved to be inactive. The ratio of cationic to hydrophobic
      residues is also important. Active beta-peptides induce the leakage of beta
      galactosidase from treated Bacillus subtilis cells, as do alpha-helical
      antibiotic peptides, and this similarity suggests that the beta-peptide mode of
      action involves disruption of microbial membranes. This class of beta-peptides is
      not degraded by proteases, which bodes well for biological applications.

PMID- 12071742
TI  - Thermodynamics of cationic lipid binding to DNA and DNA condensation: roles of
      electrostatics and hydrophobicity.
AB  - Alkylammonium binding to DNA was studied by isothermal titration calorimetry.
      Experimental data, obtained as functions of alkyl chain length, salt
      concentration, DNA concentration, and temperature, provided a detailed
      thermodynamic description of lipid-DNA binding reactions leading to DNA
      condensation. Lipid binding, counterion displacement, and DNA condensation were
      highly cooperative processes, driven by a large increase in entropy and opposed
      by a relatively small endothermic enthalpy at room temperature. Large negative
      heat capacity change indicated a contribution from hydrophobic interactions
      between aliphatic tails. An approximation of lipid-DNA binding as dominated by
      two factors-ionic and hydrophobic interactions-yielded a model that was
      consistent with experimental data. Chemical group contributions to the energetics
      of binding were determined and could be used to predict energetics of other lipid
      binding to DNA. Electrostatic and hydrophobic contributions to Gibbs free energy,
      enthalpy, entropy, and heat capacity could be distinguished by applying
      additivity principles. Binding of lipids with two, three, and four aliphatic
      tails was investigated and compared to single-tailed lipid binding. Structurally,
      the model suggests that lipid cationic headgroups and aliphatic tails distribute
      evenly and lay down on DNA surface without the formation of micelles.

PMID- 12071743
TI  - C2-hydroxyglycosylation with glycal donors. Probing the mechanism of sulfonium
      mediated oxygen transfer to glycal enol ethers.
AB  - The C2-hydroxyglycosylation reaction employing the reagent combination of a
      diaryl sulfoxide and triflic anhydride offers a novel method for glycal assembly
      whereby a hydroxyl functionality is stereoselectively installed at the C2
      position of a glycal donor with concomitant glycosylation of a nucleophilic
      acceptor. Mechanistic investigations into this reaction revealed a novel process
      for sulfonium-mediated oxidation of glycal enol ethers in which the sulfoxide
      oxygen atom is stereoselectively transferred to the C2-position of the glycal.
      (18)O-labeling studies revealed that the S-to-C2 oxygen-transfer process involves
      initial formation of a C1[bond]O linkage followed by O-migration to C2, leading
      to the generation of an intermediate glycosyl 1,2-anhydropyranoside that serves
      as an in situ glycosylating agent. These findings are consistent with the initial
      formation of a C2-sulfonium[bond]C1-oxosulfonium pyranosyl species upon
      activation of the glycal donor with Aryl(2)SO x Tf(2)O.

PMID- 12071744
TI  - Gas-phase concentration, purification, and identification of whole proteins from
      complex mixtures.
AB  - Five proteins present in a relatively complex mixture derived from a whole cell
      lysate fraction of E. coli have been concentrated, purified, and dissociated in
      the gas phase, using a quadrupole ion trap mass spectrometer. Concentration of
      intact protein ions was effected using gas-phase ion/ion proton-transfer
      reactions in conjunction with mass-to-charge dependent ion "parking" to
      accumulate protein ions initially dispersed over a range of charge states into a
      single lower charge state. Sequential ion isolation events interspersed with
      additional ion parking ion/ion reaction periods were used to "charge-state
      purify" the protein ion of interest. Five of the most abundant protein components
      present in the mixture were subjected to this concentration/purification
      procedure and then dissociated by collisional activation of their intact multiply
      charged precursor ions. Four of the five proteins were subsequently identified by
      matching the uninterpreted product ion spectra against a partially annotated
      protein sequence database, coupled with a novel scoring scheme weighted for the
      relative abundances of the experimentally observed product ions and the frequency
      of fragmentations occurring at preferential cleavage sites. The identification of
      these proteins illustrates the potential of this "top-down" protein
      identification approach to reduce the reliance on condensed-phase chemistries and
      extensive separations for complex protein mixture analysis.

PMID- 12071746
TI  - Formation of vinyl halides via a ruthenium-catalyzed three-component coupling.
AB  - The ruthenium-catalyzed three-component coupling of an alkyne, an enone, and
      halide ion to form E- or Z-vinyl halides has been investigated. Through
      systematic optimization experiments, the conditions effecting the olefin
      selectivity were examined. In general, more polar solvents such as DMF favored
      the formation of the E-isomer, and less polar solvents such as acetone favored
      formation of the Z-isomer. The optimized conditions for the formation of E-vinyl
      chlorides were found to be the use of cyclopentadienyl ruthenium (II)
      cyclooctadiene chloride, stannic chloride pentahydrate as a cocatalyst, and for a
      chloride source, either ammonium chloride in DMF/water mixtures or
      tetramethylammonium chloride in DMF. A range of several other ruthenium (II)
      catalysts was also shown to be effective. A wide variety of vinyl chlorides could
      be formed under these conditions. Substrates with tethered alcohols or ketones
      either five or six carbons from the alkyne portion gave instead diketone or
      cyclohexenone products. For formation of vinyl bromides, a catalyst system
      involving the use of cyclopentadienylruthenium (II) tris(acetonitrile)
      hexafluorophosphate with stannic bromide as a cocatalyst was found to be most
      effective. The use of ammonium bromide in DMF/acetone mixtures was optimal for
      the synthesis of E-vinyl bromides, and the use of lithium bromide in acetone was
      optimal for formation of the corresponding Z-isomer. Under either set of
      conditions, a wide range of vinyl bromides could be formed. When alkynes with
      propargylic substituents are used, enhanced selectivity for formation of the Z
      isomer is observed. When aryl acetylenes are used as the coupling partners,
      complete selectivity for the Z-isomer is obtained. A mechanism involving a cis or
      trans halometalation is invoked to explain formation of the observed products.
      The vinyl halides have been shown to be precursors to alpha-hydroxy ketones and
      cyclopentenones, and as coupling partners in Suzuki-type reactions.

PMID- 12071747
TI  - Electrostatic modulation by ionic aggregates: charge transfer transitions in
      solutions of lithium perchlorate-diethyl ether.
AB  - The ionic environment within solutions of lithium perchlorate-diethyl ether
      (LPDE) was probed by utilizing the extraordinary spectral shifts these media
      impart on various nitroanilines at 25 degrees C. These compounds all have UV
      visible spectra that are sensitive to the polarity of the medium and the
      nitroanilines investigated all exhibited varying degrees of solvatochromatic
      behavior in LPDE solutions. In all cases, the low-energy absorbance band
      exhibited a dependence upon LiClO(4) concentration throughout the entire
      solubility range investigated. For 4-nitroaniline and N,N-dimethyl-4-nitroaniline
      bathochromic shifts of 51.3 and 62.0 nm, respectively, were observed on going
      from pure ether to a 5.7 M LPDE solution, corresponding to a stabilization of
      10.55 and 11.13 kcal mol(-1), respectively, for this transition. Thus, as the
      medium changes from diethyl ether to one containing ionic clusters of lithium
      perchlorate-diethyl ether, less energy is required to transfer the molecules from
      their ground states to their first excited states. For 2,6-dibromo- and 2,6
      diiodo-4-nitroaniline smaller red shifts of 19.0 and 9.0 nm, respectively, were
      noted over the same concentration range of LPDE, resulting in stabilizations of
      4.45 and 2.11 kcal mol(-1), respectively. Analysis of the observed molar
      transition energies indicates that for 4-nitroaniline and N,N-dimethyl-4
      nitroaniline the stabilization of the zwitterionic excited states of such push
      pull molecules is on the order of 2.0 kcal mol(-1) per mol of added salt.
      Furthermore, such stabilization is independent of the composition of the media.
      Thus these compounds can act as solvent polarity indicators for LPDE solutions
      throughout the entire solubility range of LiClO(4) in diethyl ether. As such,
      linear relationships are seen between the E(T) values of 4-nitroaniline and N,N
      dimethyl-4-nitroaniline and the log of the second-order rate constants for the
      [4+2] cycloaddition reaction of 9,10-dimethylanthracene and acrylonitrile in
      LPDE. We also observe linear relationships between the E(T) values of 4
      nitroaniline and N,N-dimethyl-4-nitroaniline and the keto-enol ratio of
      acetylacetone in LPDE.

PMID- 12071745
TI  - Silicon-based metalloprotease inhibitors: synthesis and evaluation of silanol and
      silanediol peptide analogues as inhibitors of angiotensin-converting enzyme.
AB  - Silanols are best known as unstable precursors of siloxane (silicone) polymers,
      substances generally considered stable and inert, but have the potential to mimic
      a hydrated carbonyl and inhibit protease enzymes. While previous testing of
      simple silanediol and silanetriol species as inhibitors of hydrolase enzymes
      found them ineffective, this study reports polypeptide mimics with a central
      methylsilanol [SiMeOH] or silanediol [Si(OH)(2)] group and their assessment as
      effective transition state analogue inhibitors of the well-studied
      metalloprotease angiotensin-converting enzyme (ACE). Central to the synthesis
      strategy, phenylsilanes were employed as acid-hydrolyzable precursors of the
      silanol group. The N-benzoyl Leu-[SiMeOH]-Gly benzyl amides proved to be stable
      and readily characterized. In contrast, the Leu-[Si(OH)(2)]-Gly structure was
      difficult to characterize, possibly because of self-association. Capping the
      silanediol with chlorotrimethylsilane gave a well-defined trisiloxane,
      demonstrating that the silanediol was monomeric. The Leu-[Si]-Gly structures were
      converted to Leu-[Si]-Ala analogues by enolate alkylation. Coupling of the
      silanol precursors with proline tert-butyl ester gave N-benzoyl Leu-[Si]-Gly-Pro
      and N-benzoyl Leu-[Si]-Ala-Pro tripeptide analogues. Treatment of these with
      triflic acid formed the corresponding methylsilanols and silanediols, all of
      which were monomeric. The silanediol tripeptide mimics inhibited ACE with IC(50)
      values as low as 14 nM. Methylsilanols, in contrast, were poor inhibitors, with
      IC(50) values above 3000 nM. These data, including comparisons with inhibition
      data from carbon analogues, are consistent with binding of the silanediols by
      chelation of the ACE active site zinc, whereas the methylsilanols ligate poorly.

PMID- 12071748
TI  - Cycloaddition reactions of dihapto-coordinated furans.
AB  - Complexes of the type [TpRe(CO)(L)(eta(2)-furan)], where Tp =
      hydridotris(pyrazolyl)borate and L = PMe(3) (1) or (t)BuNC (2), undergo dipolar
      cycloadditions with TCNE (tetracyanoethylene) to afford 7-oxabicycloheptene
      complexes 3 and 4, respectively. The corresponding 2-methylfuran complexes (5 and
      7) for these L ligands give similar methyloxabicycloheptene complexes (6 and 8),
      with a diastereomer ratio >20:1 for 8. For L = N-methylimidazole (MeIm, 9), TCNE
      oxidizes the complex, but cycloadditions can be achieved with DMAD (dimethyl
      acetylenedicarboxylate) as the electrophile. Three complexes are observed: one in
      which DMAD undergoes a cycloaddition with the carbonyl ylide form of the complex
      (10C), and two complexes that are coordination diastereomers where DMAD has
      undergone a formal [2+2] cycloaddition with the uncoordinated double bond of the
      4,5-eta(2)-furan ligand (10B and 10A). With the imidazole complex of 2
      methylfuran (11), only the [2+2] products (12B and 12A) are observed. In the case
      of the 2,5-dimethylfuran complex (L = MeIm, 13), which is formed as a single
      coordination diastereomer, only one [2+2] product is observed (14), the structure
      of which was confirmed by X-ray crystallography. Oxidative decomplexation of 14
      results in liberation of the free oxabicyclo[3.2.0]heptadiene 15, which can be
      thermally converted to the corresponding oxepin 16 in 70% yield.

PMID- 12071749
TI  - Toward computing relative configurations: 16-epi-latrunculin B, a new
      stereoisomer of the actin polymerization inhibitor latrunculin B.
AB  - The title compound, 16-epi-latrunculin B (3), has been isolated from the sponge
      Negombata magnifica collected from the Red Sea near Hurghada, Egypt. This new
      natural product was determined to be an epimer of latrunculin B (1), which was
      found in the same sponge collection. The structure of 3 was initially deduced
      from proton and carbon NMR chemical shift trends and proton-proton nuclear
      Overhauser effect experiments. The cytotoxicity (murine tumor and normal cell
      lines) and antiviral (HSV-1) properties of 3 and 1 were determined. A
      computational study applicable to this class of stereochemical problems was then
      investigated. Specifically, the complete set of vicinal and allylic coupling
      constants was calculated for each of the four diastereomers whose configurations
      differed at C(8) and C(16). These computed J's were then compared with the
      experimental J values (28 in number) determined for 1 and 3. This analysis
      resulted in the same assignment of relative configuration for compound 3 reached
      using the more classical methods. The validity of the method is established by
      the fact that the 28 computed coupling constants for (known) 1 and (newly
      determined) 3 varied from the experimental J values with an average of just 0.57
      and 0.53 Hz, respectively. This strategy represents a general, powerful, and
      readily adoptable tool for determining the relative configuration of complex
      molecules.

PMID- 12071750
TI  - Selective substitution of corroles: nitration, hydroformylation, and
      chlorosulfonation.
AB  - This work demonstrates the feasibility and power of electrophilic substitution on
      the peripheral carbon atoms of triarylcorroles as a synthetic tool to new
      derivatives. The large difference in the reactivity of the various carbon atoms
      on the macrocycle was shown to be of electronic rather than steric origin. A
      careful choice of reagents and a delicate control of reaction conditions allowed
      the selective syntheses of novel derivatives, in all of which substitution took
      place selectively in only the directly joined pyrrole rings of the macrocycle.
      This was proven by a combination of X-ray crystallography of the various products
      and detailed analysis of their NMR spectra.

PMID- 12071752
TI  - Structural chemistry of arachno-nonaboranes.
AB  - Single-crystal conventional-tube and synchrotron X-ray diffraction studies of the
      anions in [NMe(4)][arachno-B(9)H(12)-4,8-Br(2)] 1 and K[arachno-B(9)H(14)] 2, and
      also of the series of adducts [arachno-B(9)H(13)-4-L], where L is P(CCH)(3) (3),
      NHEt(2) (4), NC(5)H(5) (5), or NH(2)CH(2)Ph (6), are reported. Structural studies
      of 1-6, determined at low temperatures, located all atoms, including bridging and
      endo-terminal hydrogen atoms. The basic boron-hydride clusters of these, and of
      all the other known species with the arachno nine-vertex i-nonanborane geometry
      reported in the literature, are isostructural and feature three bridging and two
      endo-terminal hydrogen atoms on the open face. This arrangement is different from
      that previously reported for Cs[arachno-B(9)H(14)] 7 and for [arachno-B(9)H(13)-4
      (NCMe)] 9. However, a new X-ray diffraction data set and refinement
      experimentally confirm the [3 x mu-H, 2 x endo] arrangement for 9 also. The
      experimental results for 1-6 support recently reported calculations for
      [B(9)H(14)](-), which predict both the structures and the (11)B NMR chemical
      shifts. These conclusions are also supported by calculations for 3, 4, and 9 and
      also for the [arachno-B(9)H(13)-4-(NCS)](-) anion in [NMe(4)][B(9)H(13)(NCS)] 8.

PMID- 12071751
TI  - A general and efficient copper catalyst for the amidation of aryl halides.
AB  - An experimentally simple and inexpensive catalyst system was developed for the
      amidation of aryl halides by using 0.2-10 mol % of CuI, 5-20 mol % of a 1,2
      diamine ligand, and K(3)PO(4), K(2)CO(3), or Cs(2)CO(3) as base. Catalyst systems
      based on N,N'-dimethylethylenediamine or trans-N,N'-dimethyl-1,2
      cyclohexanediamine were found to be the most active even though several other 1,2
      diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and
      in some cases even aryl chlorides can be efficiently amidated. A variety of
      functional groups are tolerated in the reaction, including many that are not
      compatible with Pd-catalyzed amidation or amination methodology.

PMID- 12071753
TI  - Cross-coupling reaction of alpha-chloroketones and organotin enolates catalyzed
      by zinc halides for synthesis of gamma-diketones.
AB  - The reaction of tin enolates 1 with alpha-chloro- or bromoketones 2 gave gamma
      diketones (1,4-diketones) 3 catalyzed by zinc halides. In contrast to the
      exclusive formation of 1,4-diketones 3 under catalytic conditions, uncatalyzed
      reaction of 1 with 2 gave aldol-type products 4 through carbonyl attack. NMR
      study indicates that the catalyzed reaction includes precondensation between tin
      enolates and alpha-haloketones providing an aldol-type species and their
      rearrangement of the oxoalkyl group with leaving halogen to produce 1,4
      diketones. The catalyst, zinc halides, plays an important role in each step. The
      carbonyl attack for precondensation is accelerated by the catalyst as Lewis acid
      and the intermediate zincate promotes the rearrangement by releasing oxygen and
      bonding with halogen. Various types of tin enolates and alpha-chloro- and
      bromoketones were applied to the zinc-catalyzed cross-coupling. On the other
      hand, the allylic halides, which have no carbonyl moiety, were inert to the zinc
      catalyzed coupling with tin enolates. The copper halides showed high catalytic
      activity for the coupling between tin enolates 1 and organic halides 7 to give
      gamma,delta-unsaturated ketones 8 and/or 9. The reaction with even chlorides
      proceeded effectively by the catalytic system.

PMID- 12071754
TI  - Macromolecular chirality induction on optically inactive poly(4-carboxyphenyl
      isocyanide) with chiral amines: a dynamic conformational transition of
      poly(phenyl isocyanide) derivatives.
AB  - Optically active polyisocyanides (poly(iminomethylenes)) have been prepared with
      much interest in developing new functional materials. Polyisocyanides have been
      considered to have a stable 4(1) helical conformation even in solution when they
      have a bulky side group. However, the conformational characteristics of
      poly(phenyl isocyanide) (PPI) derivatives are still under debate. We now report
      that an optically inactive PPI derivative, poly(4-carboxyphenyl isocyanide) (poly
      1), shows optical activity in the polymer backbone induced by external, chiral
      stimuli through acid-base interactions under thermodynamic control and exhibits
      induced circular dichroism (ICD) in the UV-visible region in DMSO. The ICD
      intensities of the poly-1-chiral amine complexes in DMSO gradually increased with
      time, and, in one case, the value reached 3 times that of the original value
      after 2 months at 30 degrees C. The conformational changes also occurred very
      slowly for poly-1 alone and its ethyl ester with time on the basis of (1)H NMR
      spectroscopic analysis. These results indicate that PPIs bearing a less bulky
      substituent may not have a 4(1) helical conformation but have a different type of
      prochiral conformation, for instance, an s-trans (zigzag) structure which may
      transform to a dynamic, one-handed helical conformation when the PPIs have a
      functional group capable of interacting with chiral compounds. The mechanism of
      helicity induction on poly-1 through a dynamic conformational transition is
      discussed on the basis of the above results together with molecular dynamic
      simulation results for PPI.

PMID- 12071756
TI  - The solute-solvent system: solvent constraints on the conformational dynamics of
      acetylcholine.
AB  - The objective of this study was to determine if and how a solvent influences
      internal motions in a solute molecule. Acetylcholine was chosen as the object of
      study given its interesting molecular structure and major biological
      significance. Molecular dynamics simulations were carried out in the vacuum (10
      ns), water (5 ns), methanol (5 ns), and octanol (1.5 ns). Seven clusters of
      conformers were identified, namely, +g+g, -g-g, +gt, -gt, t+g, t-g, and tt, where
      the gauche and trans labels refer to the dihedral angles tau(2) and tau(3),
      respectively. As expected, the relative proportion of these conformational
      clusters was highly solvent-dependent and corresponded to a progressive loss of
      conformational freedom with increasing molecular weight of the solvent. More
      importantly, the conformational clusters were used to calculate instantaneous and
      median angular velocity (omega and omega(M), respectively) and instantaneous and
      median angular acceleration (alpha and alpha(M), respectively). Angular velocity
      and angular acceleration were both found to decrease markedly with increasing
      molecular weight of the solvent, i.e., vacuum (epsilon = 1) > water > methanol >
      octanol. The decrease from the vacuum to octanol was approximately 40% for tau(2)
      and approximately 60% for tau(3). Such solvent-dependent constraints on a
      solute's internal motions may be biologically and pharmacologically relevant.

PMID- 12071755
TI  - The Mn cluster in the S(0) state of the oxygen-evolving complex of photosystem II
      studied by EXAFS spectroscopy: are there three Di-mu-oxo-bridged Mn(2) moieties
      in the tetranuclear Mn complex?
AB  - A key component required for an understanding of the mechanism of the evolution
      of molecular oxygen by the photosynthetic oxygen-evolving complex (OEC) in
      photosystem II (PS II) is the knowledge of the structures of the Mn cluster in
      the OEC in each of its intermediate redox states, or S-states. In this paper, we
      report the first detailed structural characterization using Mn extended X-ray
      absorption fine structure (EXAFS) spectroscopy of the Mn cluster of the OEC in
      the S(0) state, which exists immediately after the release of molecular oxygen.
      On the basis of the EXAFS spectroscopic results, the most likely interpretation
      is that one of the di-mu-oxo-bridged Mn-Mn moieties in the OEC has increased in
      distance from 2.7 A in the dark-stable S(1) state to 2.85 A in the S(0) state.
      Furthermore, curve fitting of the distance heterogeneity present in the EXAFS
      data from the S(0) state leads to the intriguing possibility that three di-mu-oxo
      bridged Mn-Mn moieties may exist in the OEC instead of the two di-mu-oxo-bridged
      Mn-Mn moieties that are widely used in proposed structural models for the OEC.
      This possibility is developed using novel structural models for the Mn cluster in
      the OEC which are consistent with the structural information available from EXAFS
      and the recent X-ray crystallographic structure of PS II at 3.8 A resolution.

PMID- 12071757
TI  - Diheteroarylethenes as thermally stable photoswitchable acceptors in photochromic
      fluorescence resonance energy transfer (pcFRET).
AB  - We have employed diheteroarylethenes as acceptors for photochromic FRET (pcFRET),
      a technique introduced for the quantitative determination of fluorescence
      resonance energy transfer (FRET). In pcFRET, the fluorescent emission of the
      donor is modulated by cyclical transformations of a photochromic acceptor. Light
      induces a reversible change in the structure and, concomitantly, in the
      absorption properties of the acceptor. Only the closed forms of the selected
      diheteroarylethenes 2a and 2b have an absorption band overlapping the emission
      band of the donor, 1. The corresponding variation in the overlap integral (and
      thus critical transfer distance R(o)) between the two states provides the means
      for reversibly switching the process of FRET on and off, allowing direct and
      repeated evaluation of the relative changes in the donor fluorescence quantum
      yield. The diheteroarylethenes demonstrate excellent stability in aqueous media,
      an absence of thermal back reactions, and negligible fatigue. The equilibration
      of these systems after exposure to near-UV or visible light follows simple
      monoexponential kinetics. We developed a general conceptual scheme for such
      coupled photochromic-FRET reactions, allowing quantitative interpretations of the
      photostationary and kinetic data, from which the quantum yields for the
      cyclization and cycloreversion reactions of the photochromic acceptor were
      calculated.

PMID- 12071758
TI  - Improper or classical hydrogen bonding? A comparative cryosolutions infrared
      study of the complexes of HCClF(2), HCCl(2)F, and HCCl(3) with dimethyl ether.
AB  - Complexes of haloforms of the type HCCl(n)F(3-)(n) (n = 1-3) with dimethyl ether
      have been studied in liquid argon and liquid krypton, using infrared
      spectroscopy. For the haloform C[bond]H stretching mode, the complexation causes
      blue shifts of 10.6 and 4.8 cm(-1) for HCClF(2) and HCCl(2)F, respectively, while
      for HCCl(3) a red shift of 8.3 cm(-1) is observed. The ratio of the band areas of
      the haloform C[bond]H stretching in complex and monomer was determined to be
      0.86(4) for HCClF(2), 33(3) for HCCl(2)F, and 56(3) for HCCl(3). These
      observations, combined with those for the HCF(3) complex with the same ether (J.
      Am. Chem. Soc. 2001, 123, 12290), have been analyzed using ab initio calculations
      at the MP2[double bond]FC/6-31G(d) level, and using some recent models for
      improper hydrogen bonding. Ab initio calculations on the haloforms embedded in a
      homogeneous electric field to model the influence of the ether suggest that the
      complexation shift of the haloform C[bond]H stretching is largely explained by
      the electric field effect induced by the electron donor in the proton donor. The
      model calculations also show that the electric field effect accounts for the
      observed intensity changes of the haloform C[bond]H stretches.

PMID- 12071759
TI  - Coadsorption of CO and O(2) on selected gold clusters: evidence for efficient
      room-temperature CO(2) generation.
AB  - Spurred by the recent demonstrations of the size- and support-dependent
      reactivity of supported gold clusters, here we present results on the
      coadsorption of CO and O(2) on selected anionic gold clusters, Au(N)(-), in the
      gas phase. O(2) adsorbs in a binary (0,1) fashion as a one-electron acceptor on
      the Au(N)()(-) clusters, with even-N clusters showing varying reactivity toward
      O(2) adsorption, while odd-N clusters show no evidence of reactivity. CO shows a
      highly size-dependent reactivity for Au(N)(-) sizes from N = 4 to 19, but no
      adsorption on the gold dimer or trimer. When the gold clusters are exposed to
      both reactants, either simultaneously or sequentially, interesting effects have
      been observed. While the same rules pertaining to individual O(2) or CO
      adsorption continue to apply, the preadsorption of one reactant on a cluster may
      lead to the increased reactivity of the cluster to the other reactant. Thus, the
      adsorbates are not competing for bonding sites (competitive coadsorption), but,
      instead, aid in the adsorption of one another (cooperative coadsorption). New
      peaks also arise in the mass spectrum of Au(6)(-) under CO and O(2) coadsorption
      conditions, which can be attributed to the loss of a CO(2) molecule (or
      molecules). By studying the relative amount of reaction, and relating it to the
      reaction time, it is found that the gas-phase Au(6) anion is capable of oxidizing
      CO at a rate 100 times that reported for commercial or model gold catalysts.

PMID- 12071761
TI  - CP/MAS (13)C NMR study of cellulose and cellulose derivatives. 2. Complete
      assignment of the (13)C resonance for the ring carbons of cellulose triacetate
      polymorphs.
AB  - Complex ring (13)C resonance lines of the cross-polarization/magic angle spinning
      (CP/MAS) (13)C NMR spectra of cellulose triacetate (CTA) I and CTA II were
      completely assigned, for the first time, by (13)C-enriched CTA allomorphs. The
      (13)C-enriched CTA I was prepared by heterogeneous acetylation of bacterial
      cellulose which was biosynthesized by Acetobacter xylinum (A. xylinum) ATCC10245
      from culture medium containing D-(2-(13)C)-, D-(3-(13)C)-, or D-(5-(13)C)glucose
      as a carbon source, while CTA II samples were obtained by solution acetylation of
      the (13)C-enriched bacterial celluloses. From comparison of the spectra of normal
      CTA prepared from ramie with those of the enriched CTA samples, it was revealed
      that all carbons composed of CTA I appeared as a singlet, while those of CTA II
      except for C1 were shown as equal-intensity doublets in the CP/MAS (13)C NMR
      spectrum. This finding suggests that CTA I is made up of one kind of
      glucopyranose residue while there are two magnetically inequivalent sites in the
      unit cell of CTA II in the same population.

PMID- 12071760
TI  - CP/MAS (13)C NMR study of cellulose and cellulose derivatives. 1. Complete
      assignment of the CP/MAS (13)C NMR spectrum of the native cellulose.
AB  - The precise assignments of cross polarization/magic angle spinning (CP/MAS) (13)C
      NMR spectra of cellulose I(alpha) and I(beta) were performed by using (13)C
      labeled cellulose biosynthesized by Acetobacter xylinum (A. xylinum) ATCC10245
      strain from culture medium containing D-[1,3-(13)C]glycerol or D-[2-(13)C]glucose
      as a carbon source. On the CP/MAS (13)C NMR spectrum of cellulose from D-[1,3
      (13)C]glycerol, the introduced (13)C labeling were observed at C1, C3, C4, and C6
      of the biosynthesized cellulose. In the case of cellulose biosynthesized from D
      [2-(13)C]glucose, the transitions of (13)C labeling to C1, C3, and C5 from C2
      were observed. With the quantitative analysis of the (13)C transition ratio and
      comparing the CP/MAS (13)C NMR spectrum of the Cladophora cellulose with those of
      the (13)C labeled celluloses, the assignments of the cluster of resonances which
      belong to C2, C3, and C5 of cellulose, which have not been assigned before, were
      performed. As a result, all carbons of cellulose I(alpha) and I(beta) except for
      C1 and C6 of cellulose I(alpha) and C2 of cellulose I(beta) were shown in equal
      intensity of doublet in the CP/MAS spectrum of the native cellulose, which
      suggests that two inequivalent glucopyranose residues were contained in the unit
      cells of both cellulose I(alpha) and I(beta) allomorphs.

PMID- 12071762
TI  - Stochastic simulations of polymer growth and isomerization in the polymerization
      of propylene catalyzed by Pd-based diimine catalysts.
AB  - A model is presented that employs a stochastic approach to the simulation of
      polyolefin chain growth and isomerization. The model is applied to propylene
      polymerization catalyzed by Pd-based diimine catalysts. The stochastic approach
      links the microscopic (quantum chemical) approach with modeling of the
      macroscopic systems. The DFT calculated energies of the elementary reactions and
      their barriers have been used as input parameters for the simulations. The
      influence of the catalyst's steric bulk, as well as polymerization temperature
      and olefin pressure on the polymer branching and its microstructure, is
      discussed. The results are in good agreement with available experimental data. In
      the propylene polymerization catalyzed by Pd(II) complexes with methyl backbone-
      and -Ph-(i)Pr(2) imine substituents a number of branches of 238 branches/1000 C
      have been obtained. An increase in polymerization temperature leads to a decrease
      in the number of branches. Change in olefin pressure does not affect the global
      number of branches, while it strongly affects the polymer microstructure, leading
      to hyperbranched structures at low pressures. Further, the simulations confirm
      the experimental interpretation of the mechanistic details for this process: (1)
      both 1,2- and 2,1-insertion happen with the ratio of ca. 7:3; (2) there are no
      insertions at the secondary carbons; and (3) most of the 2,1-insertions are
      followed by a chain straightening isomerization. Thus, for this catalyst the
      total number of branches is controlled exclusively by the 1,2-/2,1-insertion
      ratio. For the catalysts with different substituents the branching can be
      controlled by a 1,2-/2,1-insertion ratio as well as the fraction of the
      insertions at the secondary carbons. The results of the present studies
      demonstrate that a stochastic approach can be successfully used to model the
      polyolefin microstructures and their catalyst, temperature, and pressure
      dependence. Further, it can also facilitate interpretation of the experimental
      results, and can be used to draw general conclusions about the influence of the
      specific elementary reaction barriers on the polymer structures; this can be
      helpful for a rational design of the catalysts producing a desired
      microstructure.

PMID- 12071763
TI  - Theoretical and electrochemical analysis of dissociative electron transfers
      proceeding through formation of loose radical anion species: reduction of
      symmetrical and unsymmetrical disulfides.
AB  - The dissociative reduction of a series of symmetrical (RSSR, R = H, Me, t-Bu, Ph)
      and unsymmetrical disulfides (RSSR', R = H, R' = Me and R = Ph, R' = Me, t-Bu)
      was studied theoretically, by MO ab initio calculations and, for five of them,
      also experimentally, by convolution voltammetry in N,N-dimethylformamide. The
      reduction is dissociative but proceeds by a stepwise mechanism entailing the
      formation of the radical anion species. The electrochemical data led to estimated
      large intrinsic barriers, in agreement with an unusually large structural
      modification undergone by the disulfide molecules upon electron transfer. The
      theoretical results refer to MP2/3-21G*//MP2/3-21G*, MP2/3-21*G*//MP2/3-21G*, CBS
      4M, and G2(MP2), the latter approach being used only for the molecules of small
      molecular complexity. A loose radical-anion intermediate was localized and the
      dissociation pattern for the relevant bonds analyzed. For all compounds, the best
      fragmentation pathway in solution is cleavage of the S-S bond. In addition, S-S
      bond elongation is the major structural modification undergone by the disulfide
      molecule on its way to the radical anion and eventually to the fragmentation
      products. The calculated energy of activation for the initial electron transfer
      was estimated from the crossing of the energy profiles of the neutral molecule
      and its radical anion (in the form of Morse-like potentials) as a function of the
      S-S bond length coordinate. The inner intrinsic barrier obtained in this way is
      in good agreement with that determined by convolution voltammetry, once the
      solvent effect is taken into account.

PMID- 12071764
TI  - Excited state proton transfer in reverse micelles.
AB  - The aqueous phase of water/AOT reversed micelles having varying diameters was
      probed by a single free diffusing proton that was released form a hydrophilic
      photoacid molecule (2-naphthol-6,8-disulfonate). The fluorescence decay signals
      were reconstructed through the geminate recombination algorithm, accounting for
      the reversible nature of the proton-transfer reactions at the surface of the
      excited molecule and at the water/detergent interface. The radial diffusion of
      the proton inside the aqueous phase was calculated accounting for both the
      entropy of dilution and the total electrostatic energy of the ion pair,
      consisting of the pair-energy and self-energy of the ions. The analysis implied
      that micellar surface must be modeled with atomic resolution, assuming that the
      sulfono residue protrudes above the water/hydrocarbon interface by approximately
      2 A. The analysis of the fluorescence decay curves implies that the molecule is
      located in a solvent with physical-chemical properties very similar to bulk
      water, except for the dielectric constant. For reversed micelles with r(max) > or
      = 16 A, the dielectric constant of the aqueous phase was approximately 70 and for
      smaller micelles, where approximately 60% of the water molecule is in contact
      with the van der Waals surface of the micelle, it is as low as 60. This reduction
      is a reflection of the increased fraction of water molecule that is in close
      interaction with the micelle surface.

PMID- 12071765
TI  - Formation and decomposition of N,N,N-trimethylanilinium cations on zeolite H-Y
      investigated by in situ stopped-flow MAS NMR spectroscopy.
AB  - Methylation of aniline by methanol on zeolite H-Y has been investigated by in
      situ (13)C MAS NMR spectroscopy under flow conditions. The in situ (13)C
      continuous-flow (CF) MAS NMR experiments were performed at reaction temperatures
      between 473 and 523 K, molar methanol-to-aniline ratios of 1:1 to 4:1, and
      modified residence times of (13)CH(3)OH between 20 and 100 (g x h)/mol. The
      methylation reaction was shown to start at 473 K. N,N,N-Trimethylanilinium
      cations causing a (13)C NMR signal at 58 ppm constitute the major product on the
      catalyst surface. Small amounts of protonated N-methylaniline ([PhNH(2)CH(3)](+))
      and N,N-dimethylaniline ([PhNH(CH(3))(2)](+)) were also observed at ca. 39 and 48
      ppm, respectively. After increase of the temperature to 523 K, the contents of
      N,N-dimethylanilinium cations and ring-alkylated reaction products strongly
      increased, accompanied by a decrease of the amount of N,N,N-trimethylanilinium
      cations. With application of the in situ stopped-flow (SF) MAS NMR technique, the
      decomposition of N,N,N-trimethylanilinium cations on zeolite H-Y to N,N
      dimethylanilinium and N-methylanilinium cations was investigated to gain a deeper
      insight into the reaction mechanism. The results obtained allow the proposal of a
      mechanism consisting of three steps: (i) the conversion of methanol to surface
      methoxy groups and dimethyl ether (DME); (ii) the alkylation of aniline with
      methanol, methoxy groups, or DME leading to an equilibrium mixture of N,N,N
      trimethylanilinium, N,N-dimethylanilinium, and N-methylanilinium cations attached
      to the zeolite surface; (iii) the deprotonation of N,N-dimethylanilinium and N
      methylanilinium cations causing the formation of N,N-dimethylaniline (NNDMA) and
      N-methylaniline (NMA) in the gas phase, respectively. The chemical equilibrium
      between the anilinium cations carrying different numbers of methyl groups is
      suggested to play a key role for the products distribution in the gas phase.

PMID- 12071766
TI  - First gas-phase detection of dimethylstannylene and time-resolved study of some
      of its reactions.
AB  - Using a laser flash photolysis/laser probe technique, we report the observation
      of strong absorption signals in the wavelength region 450-520 nm (highest
      intensity at 514.5 nm) from four potential precursors of dimethylstannylene,
      SnMe(2), subjected to 193 nm UV pulses. From GC analyses of the gaseous products,
      combined with quantum chemical excited state CIS and TD calculations, we can
      attribute these absorptions largely to SnMe(2), with SnMe(4) as the cleanest
      source of the species. Kinetic studies have been carried out by time-resolved
      monitoring of SnMe(2). Rate constants have been measured for its reactions with
      1,3-C(4)H(6), MeC[triple bond]CMe, MeOH, 1-C(4)H(9)Br, HCl, and SO(2). No
      evidence could be found for reaction of SnMe(2) with C(2)H(4), C(3)H(8),
      Me(3)SiH, GeH(4), Me(2)GeH(2), or N(2)O. Limits of less than 10(-13) cm(3)
      molecule(-1) s(-1) were set for the rate constants for these latter reactions.
      These measurements showed that SnMe(2) does not insert readily into C-H, Si-H, Ge
      H, C-C, Si-C, or Ge-C bonds. It is also unreactive with alkenes although not with
      dienes or alkynes. It is selectively reactive with lone pair donor molecules. The
      possible mechanisms of these reactions are discussed. These results represent the
      first visible absorption spectrum and rate constants for any organo-stannylene in
      the gas phase.

PMID- 12071767
TI  - From sulfoxide precursors to model oligomers of conducting polymers.
AB  - The gas-phase internal elimination (E(i)) reaction of the sulfoxide (-SO-CH(3))
      precursors of ethylene and model oligomers of PPV and PITN has been investigated
      by means of Hartree-Fock, Moller-Plesset (second and fourth order), and Density
      Functional Theory (B3LYP, MPW1K) calculations. Considerable differences between
      the obtained ground state and transition state geometries and the calculated
      activation energies are observed from one approach to the other, justifying first
      a careful calibration against the results of a benchmark CCSD(T) study of the
      E(i) reaction leading to ethylene. In comparison with the CCSD(T) results, as
      well as with available experimental data, DFT calculations along with the MPW1K
      functional are found to be a very appropriate choice for describing the E(i)
      pathway. The leading conformations of the precursors, the relevant transition
      state structures, and the energy barriers encountered along the lowest energy
      path to unsubstituted, alpha and beta chloro-, methoxy-, and cyano-substituted
      ethylene, styrene, stilbene in its cis and trans forms, and at last trans
      biisothianaphthene have therefore been identified and characterized in detail
      employing DFT (MPW1K). Depending on the substituents attached to the C(alpha) and
      C(beta) atoms, different reaction mechanisms are observed.

PMID- 12071769
TI  - Theoretical study of rhodium(III)-catalyzed hydrogenation of carbon dioxide into
      formic acid. Significant differences in reactivity among rhodium(III),
      rhodium(I), and ruthenium(II) complexes.
AB  - The title reaction was theoretically investigated, where cis
      [RhH(2)(PH(3))(3)](+) and cis-[RhH(2)(PH(3))(2)(H(2)O)](+) were adopted as models
      of the catalyst. The first step of the catalytic cycle is the CO(2) insertion
      into the Rh(III)-H bond, of which the activation barrier (E(a)) is 47.2 and 28.4
      kcal/mol in cis-[RhH(2)(PH(3))(3)](+) and cis-[RhH(2)(PH(3))(2)(H(2)O)](+),
      respectively, where DFT(B3LYP)-calculated E(a) values (kcal/mol unit) are given
      hereafter. These results indicate that an active species is not cis
      [RhH(2)(PH(3))(3)](+) but cis-[RhH(2)(PH(3))(2)(H(2)O)](+). After the CO(2)
      insertion, two reaction courses are possible. In one course, the reaction
      proceeds through isomerization (E(a) = 2.8) of [RhH(eta(1)-
      OCOH)(PH(3))(2)(H(2)O)(2)](+), five-centered H-OCOH reductive elimination (E(a) =
      2.7), and oxidative addition of H(2) to [Rh(PH(3))(2)(H(2)O)(2)](+) (E(a) = 5.8).
      In the other one, the reaction proceeds through isomerization of [RhH(eta(1)
      OCOH)(PH(3))(2)(H(2)O)(H(2))](+) (E(a) = 5.9) and six-centered sigma-bond
      metathesis of [RhH(eta(1)-OCOH)(PH(3))(2)(H(2)O)](+) with H(2) (no barrier).
      RhH(PH(3))(2)-catalyzed hydrogenation of CO(2) proceeds through CO(2) insertion
      (E(a) = 1.6) and either the isomerization of Rh(eta(1)-OCOH)(PH(3))(2)(H(2))
      (E(a) = 6.1) followed by the six-centered sigma-bond metathesis (E(a) = 0.3) or
      H(2) oxidative addition to Rh(eta(1)-OCOH)(PH(3))(2) (E(a) = 7.3) followed by
      isomerization of RhH(2)(eta(1)-OCOH)(PH(3))(2) (E(a) = 6.2) and the five-centered
      H-OCOH reductive elimination (E(a) = 1.9). From these results and our previous
      results of RuH(2)(PH(3))(4)-catalyzed hydrogenation of CO(2) (J. Am. Chem. Soc.
      2000, 122, 3867), detailed discussion is presented concerning differences among
      Rh(III), Rh(I), and Ru(II) complexes.

PMID- 12071768
TI  - Reactivity of phosphate monoester monoanions in aqueous solution. 1. Quantum
      mechanical calculations support the existence of "anionic zwitterion"
      MeO(+)(H)PO(3)(2-) as a key intermediate in the dissociative hydrolysis of the
      methyl phosphate anion.
AB  - The dissociative hydrolysis reaction of the methyl phosphate monoanion has been
      studied for the reactant species CH(3)OPO(3)H(-) (1) and CH(3)OPO(3)H(-) x H(2)O
      (1a) in the gas and aqueous phases by density functional theory (B3LYP)
      calculations. Nonspecific solvation effects were taken into account with the
      polarizable continuum model PCM either by solvating the gas-phase reaction paths
      or by performing geometry searches directly in the presence of the solvation
      correction. In agreement with previous theoretical studies, our gas-phase
      calculations indicate that proton transfer to the methoxy group of 1 is concerted
      with P-O bond cleavage. In contrast, optimizations performed with the PCM
      solvation model establish the existence of the tautomeric form
      CH(3)O(+)(H)PO(3)(2-) (2) as an intermediate, indicating that proton transfer and
      P-O bond cleavage become uncoupled in aqueous solution. The dissociative pathway
      of 1a is energetically favored over the dissociative pathway of 1 only when the
      added water molecule plays an active catalytic role in the prototropic
      rearrangement 1 <--> 2. In that case, it is found that the collapse (via P-O bond
      cleavage) of the hydrated zwitterionic form CH(3)O(+)(H)PO(3)(2-) x H(2)O (2a) is
      rate-determining. This collapse may occur by a stepwise mechanism through a very
      short-lived metaphosphate intermediate (PO(3)(-)), or by a concerted S(N)2-like
      displacement through a loose metaphosphate-like transition state. The present
      calculations do not allow a distinction to be made between these two
      alternatives, which are both in excellent agreement with experiment. The present
      study also reveals that PO(3)(-) reacts selectively with CH(3)OH and H(2)O
      nucleophiles in aqueous solution. However, the observed selectivity of
      metaphosphate is governed by solvation effects, not nucleophilicity (water being
      much more effective than methanol in capturing PO(3)(-)). This arises from a
      better solvation of the addition product H(2)O(+)PO(3)(2-) as compared to
      CH(3)O(+)(H)PO(3)(2-).

PMID- 12071770
TI  - Epitaxial electrodeposition of Fe(3)O(4) thin films on the low-index planes of
      gold.
AB  - Half-metallic ferrimagnetic materials such as Fe(3)O(4) are of interest for use
      in spintronic devices. These devices exploit both the spin and charge of an
      electron in spin-dependent charge transport. Epitaxial thin films of Fe(3)O(4)
      have been grown on the three low-index planes of gold by electrodeposition. On
      Au(110), a [110] Fe(3)O(4) orientation that is aligned with the underlying
      Au(110) substrate is observed. Thin films on Au(100) grow with three different
      orientations: [100], [111], and [511]. On Au(111), both [111] and [511]
      orientations of Fe(3)O(4) are observed. The [511] orientations are the result of
      twinning on [111] planes. A polarization value of approximately -40% at the Fermi
      level was measured by spin-polarized photoemission at room temperature for a thin
      film on Au(111).

PMID- 12071771
TI  - Homoleptic tetrahydrometalate anions MH(4)(-) (M = Sc, Y, La). Matrix infrared
      spectra and DFT calculations.
AB  - Laser-ablated Sc, Y, and La atoms react with molecular hydrogen upon condensation
      in excess argon, neon, and deuterium to produce the metal dihydride molecules and
      dihydrogen complexes MH(2) and (H(2))MH(2). The homoleptic tetrahydrometalate
      anions ScH(4)(-), YH(4)(-), and LaH(4)(-) are formed by electron capture and
      identified by isotopic substitution (D(2), HD, and H(2) + D(2) mixtures). Doping
      with CCl(4) to serve as an electron trap virtually eliminates the anion bands,
      and further supports the anion identifications. The observed vibrational
      frequencies are in agreement with the results of density functional theory
      calculations, which predict electron affinities in the 2.8-2.4 eV range for the
      (H(2))ScH(2), (H(2))YH(2), and (H(2))LaH(2) complexes, and indicate high
      stability for the MH(4)(-) (M = Sc, La, Y) anions and suggest the promise of
      synthesis on a larger scale for use as reducing agents.

PMID- 12071772
TI  - Photodissociation dynamics of various conformers of iodobutane isomer ions
      prepared selectively by vacuum ultraviolet mass-analyzed threshold ionization.
AB  - Various conformers of 1-C(4)H(9)I(+*), 2-C(4)H(9)I(+*), and i-C(4)H(9)I(+*) were
      prepared selectively by mass-analyzed threshold ionization with coherent vacuum
      ultraviolet radiation. Conformer-selective photodissociation of these ions was
      studied in the 560-730 nm spectral region, which corresponds to excitation to the
      first excited electronic state. Rapid dissociation was observed as manifested by
      noticeable laser polarization dependence of the product signals. In particular,
      photodissociation of i-C(4)H(9)I(+*) was found to be conformer specific,
      occurring without interconversion between conformers. The product's asymptote
      energies estimated from the experimental data were compared with the reaction
      enthalpies at 0 K to get information on the structures and states of products. It
      was found that a simple S(N)2-type mechanism deduced from the previous study of 1
      C(3)H(7)I(+*) was compatible with the present observations. Validity of the
      widely adopted postulate in stereochemistry that different conformations can be
      gateways to different reactions has been demonstrated in the gas phase.

PMID- 12071773
TI  - Manipulating the production and recombination of electrons during electron
      transfer: Femtosecond control of the charge-transfer-to-solvent (CTTS) dynamics
      of the sodium anion.
AB  - The scavenging of a solvated electron represents the simplest possible electron
      transfer (ET) reaction. In this work, we show how a sequence of femtosecond laser
      pulses can be used to manipulate an ET reaction that has only electronic degrees
      of freedom: the scavenging of a solvated electron by a single atom in solution.
      Solvated electrons in tetrahydrofuran are created via photodetachment using the
      charge-transfer-to-solvent (CTTS) transition of sodide (Na(-)). The CTTS process
      ejects electrons to well-defined distances, leading to three possible initial
      geometries for the back ET reaction between the solvated electrons and their
      geminate sodium atom partners (Na(0)). Electrons that are ejected within the same
      solvent cavity as the sodium atom (immediate contact pairs) undergo back ET in
      approximately 1 ps. Electrons ejected one solvent shell away from the Na(0)
      (solvent-separated contact pairs) take hundreds of picoseconds to undergo back
      ET. Electrons ejected more than one solvent shell from the sodium atom (free
      solvated electrons) do not recombine on subnanosecond time scales. We manipulate
      the back ET reaction for each of these geometries by applying a "re-excitation"
      pulse to promote the localized solvated electron ground state into a highly
      delocalized excited-state wave function in the fluid's conduction band. We find
      that re-excitation of electrons in immediate contact pairs suppresses the back ET
      reaction. The kinetics at different probe wavelengths and in different solvents
      suggest that the recombination is suppressed because the excited electrons can
      relocalize into different solvent cavities upon relaxation to the ground state.
      Roughly one-third of the re-excited electrons do not collapse back into their
      original solvent cavities, and of these, the majority relocalize into a cavity
      one solvent shell away. In contrast to the behavior of the immediate pair
      electrons, re-excitation of electrons in solvent-separated contact pairs leads to
      an early time enhancement of the back ET reaction, followed by a longer-time
      recombination suppression. The recombination enhancement results from the
      improved overlap between the electron and the Na(0) one solvent shell away due to
      the delocalization of the wave function upon re-excitation. Once the excited
      state decays, however, the enhanced back ET is shut off, and some of the re
      excited electrons relocalize even farther from their geminate partners, leading
      to a long-time suppression of the recombination; the rates for recombination
      enhancement and relocalization are comparable. Enhanced recombination is still
      observed even when the re-excitation pulse is applied hundreds of picoseconds
      after the initial CTTS photodetachment, verifying that solvent-separated contact
      pairs are long-lived, metastable entities. Taken together, all these results,
      combined with the simplicity and convenient spectroscopy of the sodide CTTS
      system, allow for an unprecedented degree of control that is a significant step
      toward building a full molecular-level picture of condensed-phase ET reactions.

PMID- 12071774
TI  - Use of screening algorithms and computer systems to efficiently signal higher
      than-expected combinations of drugs and events in the US FDA's spontaneous
      reports database.
AB  - Since 1998, the US Food and Drug Administration (FDA) has been exploring new
      automated and rapid Bayesian data mining techniques. These techniques have been
      used to systematically screen the FDA's huge MedWatch database of voluntary
      reports of adverse drug events for possible events of concern. The data mining
      method currently being used is the Multi-Item Gamma Poisson Shrinker (MGPS)
      program that replaced the Gamma Poisson Shrinker (GPS) program we originally used
      with the legacy database. The MGPS algorithm, the technical aspects of which are
      summarised in this paper, computes signal scores for pairs, and for higher-order
      (e.g. triplet, quadruplet) combinations of drugs and events that are
      significantly more frequent than their pair-wise associations would predict. MGPS
      generates consistent, redundant, and replicable signals while minimising random
      patterns. Signals are generated without using external exposure data, adverse
      event background information, or medical information on adverse drug reactions.
      The MGPS interface streamlines multiple input-output processes that previously
      had been manually integrated. The system, however, cannot distinguish between
      already-known associations and new associations, so the reviewers must filter
      these events. In addition to detecting possible serious single-drug adverse event
      problems, MGPS is currently being evaluated to detect possible synergistic
      interactions between drugs (drug interactions) and adverse events (syndromes),
      and to detect differences among subgroups defined by gender and by age, such as
      paediatrics and geriatrics. In the current data, only 3.4% of all 1.2 million
      drug-event pairs ever reported (with frequencies > or = 1) generate signals
      [lower 95% confidence interval limit of the adjusted ratios of the observed
      counts over expected (O/E) counts (denoted EB05) of > or = 2]. The total
      frequency count that contributed to signals comprised 23% (2.4 million) of the
      total number, 10.4 million of drug-event pairs reported, greatly facilitating a
      more focused follow-up and evaluation. The algorithm provides an objective,
      systematic view of the data alerting reviewers to critically important, new
      safety signals. The study of signals detected by current methods, signals stored
      in the Center for Drug Evaluation and Research's Monitoring Adverse Reports
      Tracking System, and the signals regarding cerivastatin, a cholesterol-lowering
      drug voluntarily withdrawn from the market in August 2001, exemplify the
      potential of data mining to improve early signal detection. The operating
      characteristics of data mining in detecting early safety signals, exemplified by
      studying a drug recently well characterised by large clinical trials confirms our
      experience that the signals generated by data mining have high enough specificity
      to deserve further investigation. The application of these tools may ultimately
      improve usage recommendations.

PMID- 12071775
TI  - A data mining approach for signal detection and analysis.
AB  - The WHO database contains over 2.5 million case reports, analysis of this data
      set is performed with the intention of signal detection. This paper presents an
      overview of the quantitative method used to highlight dependencies in this data
      set. The method Bayesian confidence propagation neural network (BCPNN) is used to
      highlight dependencies in the data set. The method uses Bayesian statistics
      implemented in a neural network architecture to analyse all reported drug adverse
      reaction combinations. This method is now in routine use for drug adverse
      reaction signal detection. Also this approach has been extended to highlight drug
      group effects and look for higher order dependencies in the WHO data.
      Quantitatively unexpectedly strong relationships in the data are highlighted
      relative to general reporting of suspected adverse effects; these associations
      are then clinically assessed.

PMID- 12071776
TI  - From pharmacovigilance to pharmacoperformance.
AB  - The pharmaceutical industry is going through a period of enormous upheaval, as
      new sciences, technologies and commercial pressures reshape the way in which it
      performs research and development. PwC Consulting estimates that the top 20
      companies will each need to launch between four and six times the number of drugs
      they currently produce, as well as improving the quality of those drugs, merely
      to maintain shareholder returns. This has huge implications for pharmacovigilance
      departments. More drugs means more trials, more patients and -- of course -- more
      safety reports for evaluation. The pharmacovigilance teams in most big companies
      are ill prepared for this transition being already stretched to the limit. But as
      demand for patients to participate in clinical trials increases -- with shorter
      development times, higher success rates in discovery and greater productivity --
      so companies with a poor reputation for safety will suffer. What is it then that
      companies should be doing to remain compliant and be seen to be safe in the eyes
      of the consumer? Can pharmacoepidemiology support both molecules in the
      marketplace as well as those in research and development and what is really
      needed to enable this? Key to success will be the ability to capture, analyse and
      evaluate data (from disparate sources) in real time and to make rapid decisions
      on the appropriate course of action. Putting better structures, processes and
      technological platforms in place to cope with a big increase in throughput is
      only a short-term solution yet is it enough to fulfil the objective in the long
      term of ensuring compliance and patient safety?

PMID- 12071777
TI  - Good pharmacovigilance practices: technology enabled.
AB  - The assessment of spontaneous reports is most effective it is conducted within a
      defined and rigorous process. The framework for good pharmacovigilance process
      (GPVP) is proposed as a subset of good postmarketing surveillance process
      (GPMSP), a functional structure for both a public health and corporate risk
      management strategy. GPVP has good practices that implement each step within a
      defined process. These practices are designed to efficiently and effectively
      detect and alert the drug safety professional to new and potentially important
      information on drug-associated adverse reactions. These practices are enabled by
      applied technology designed specifically for the review and assessment of
      spontaneous reports. Specific practices include rules-based triage, active query
      prompts for severe organ insults, contextual single case evaluation, statistical
      proportionality and correlational checks, case-series analyses, and templates for
      signal work-up and interpretation. These practices and the overall GPVP are
      supported by state-of-the-art web-based systems with powerful analytical engines,
      workflow and audit trials to allow validated systems support for valid drug
      safety signalling efforts. It is also important to understand that a process has
      a defined set of steps and any one cannot stand independently. Specifically,
      advanced use of technical alerting methods in isolation can mislead and allow one
      to misunderstand priorities and relative value. In the end, pharmacovigilance is
      a clinical art and a component process to the science of pharmacoepidemiology and
      risk management.

PMID- 12071778
TI  - Statistical techniques for signal generation: the Australian experience.
AB  - National voluntary reporting systems generate large volumes of clinical data
      pertinent to drug safety. Currently descriptive statistical techniques are used
      to assist in the detection of drug safety 'signals'. Australian data have been
      coded according to guidelines formulated almost 30 years ago and which have
      resulted in many drugs which are not associated with an adverse drug reaction or
      'innocent bystander' drugs being recorded as 'suspected' in individual reports.
      In this paper we explore the application of an iterative probability filtering
      algorithm titled 'PROFILE'. This serves to identify the 'signals' and remove the
      'innocent bystander' drugs, thus providing a clearer view of the drugs most
      likely to have caused the reactions. Reaction terms analysed include neutropenia,
      agranulocytosis, hypotension, hypertension, myocardial infarction, neuroleptic
      malignant syndrome, and rectal haemorrhage. In this version of PROFILE, Fishers
      exact test has been used as the statistical tool but other methods could be used
      in future. Advantages and limitations of the method and its assumptions are
      discussed together with the rationale underlying the method and suggestions for
      further enhancements.

PMID- 12071779
TI  - Automated signal generation in prescription-event monitoring.
AB  - Signal generation is a method of highlighting potential safety issues in a drug
      that then need to be investigated further. Previously automated signal generation
      has mainly been applied to spontaneous reporting systems. The Drug Safety
      Research Unit (DSRU) performs observational postmarketing studies on selected
      newly marketed medicines in England using a method known as prescription-event
      monitoring (PEM). The DSRU has investigated automated procedures for the
      generation of signals using the event data from PEM studies. Proportional
      reporting ratios (PRRs) and incidence rate ratios (IRRs) were studied as possible
      tools for signal generation in PEM data. The PEM database contains 78 completed
      studies of drugs prescribed in primary care from a variety of therapeutic
      classes. Retrospective studies were carried out to identify the implications of
      changing the comparator group of drugs, along with analysing the results at
      different levels in the DSRU's hierarchical dictionary and performing signal
      generation after 30 and 180 days of observation since starting the drug.
      Automated signal generation is a useful hypothesis generating method that is
      likely to prove to be useful both in clinical trials and postmarketing studies.
      PRRs are simple to apply and do not require a denominator. IRRs take into account
      the time subjects were exposed to the drug prior to the event of interest, and
      offers a useful, and more in depth look into the data. However, with both methods
      it is important to perform signal generation at multiple levels in the dictionary
      and with careful selection of the comparator group.

PMID- 12071780
TI  - Signal generation in the New Zealand Intensive Medicines Monitoring Programme: a
      combined clinical and statistical approach.
AB  - The New Zealand Intensive Medicines Monitoring Programme (IMMP) undertakes
      prospective observational cohort studies on selected new drugs in the early
      postmarketing period using prescription-event monitoring (PEM) methodology with
      the purpose of identifying signals of previously unrecognised ADRs and
      establishing risk profiles for each drug. Events are reviewed by a physician and
      a relationship is established between each event and the drug. The events are
      then sorted into reactions and incidents. The latter are used to assist signal
      detection and control for bias. Rates for reports, reactions and incidents are
      used to assess the adequacy of reporting, signal detection and identification of
      confounders. Most signals are identified by clinical evaluation of the reports at
      a stage when statistical analyses are unlikely to have the power to detect them
      with confidence. The incident group is used for signal detection and controlling
      for bias. A low reporting rate indicates that certain types of event are unlikely
      to be reported. A systematic review of the original case reports at the site of
      collection provides the best opportunity for early signal detection. More
      resources need to be invested in the training and support of clinical evaluators.
      Categorising events into reactions and incidents gives added value to the data.
      Rates of reporting should be quoted with the results of cohort studies to
      facilitate assessment of their power to detect new signals.

PMID- 12071781
TI  - Prescription-event monitoring in Japan (J-PEM).
AB  - In prescription-event monitoring in Japan (J-PEM), patients are identified by
      prescriptions in individual pharmacies where drugs are dispensed. The methodology
      is somewhat different to that used by the Drug Safety Research Unit in the UK, in
      that two questionnaires, one to the pharmacist and the other to the doctor are
      sent for each patient and the method of concurrent control is employed in J-PEM.
      In the data analysis, the list of events reported as a suspected reaction or a
      reason for stopping the drug is made to generate a signal. In addition, a signal
      may be generated for some events with the statistically significant difference of
      crude rates followed by the regression analysis or a follow-up study. In J-PEM,
      Medical Dictionary for Regulatory Activities (MedDRA) terminology is used for
      data entry and data analysis. Lowest level terms (LLTs) in MedDRA are used in
      data entry while a signal is generated using preferred terms (PTs). However, to
      generate a signal effectively, some PTs may be grouped as one term. In addition,
      if two terms are so similar, it may be instructed that one of those two terms is
      normally selected in data entry to avoid confusion. Many more PEM studies could
      be undertaken to determine if MedDRA can be used for effective signal generation,
      but the usefulness of MedDRA in J-PEM is still to be determined.

PMID- 12071782
TI  - Effects of coding dictionary on signal generation: a consideration of use of
      MedDRA compared with WHO-ART.
AB  - To support signal generation a terminology should facilitate recognition of
      medical conditions by using terms which represent unique concepts, providing
      appropriate, homogeneous grouping of related terms. It should allow intuitive or
      mathematical identification of adverse events reaching a threshold frequency or
      with disproportionate incidence, permit identification of important events which
      are commonly drug-related, and support recognition of new syndromes. It is
      probable that the Medical Dictionary for Regulatory Activities (MedDRA) preferred
      terms (PTs) or high level terms (HLTs) will be used to represent adverse events
      for the purposes of signal generation. A comparison with 315 WHO Adverse Reaction
      Terminology (WHO-ART) PTs showed that for about 72% of WHO-ART PTs, there were
      one or two corresponding MedDRA PTs. However, there were instances where there
      were many MedDRA PTs corresponding to single WHO-ART PTs. In many cases, MedDRA
      HLTs grouped large numbers of PTs and sometimes there could be problems when a
      single HLT comprises PTs which represent very different medical concepts, or
      conditions which differ greatly in their clinical importance. Further studies are
      needed to compare the way in which identical data sets coded with MedDRA and with
      other terminologies actually function in generating and exploring signals using
      the same methods of detection and evaluation.

PMID- 12071783
TI  - Use of measures of disproportionality in pharmacovigilance: three Dutch examples.
AB  - Spontaneous reporting systems for suspected adverse drug reactions (ADRs) remain
      a cornerstone of pharmacovigilance. In The Netherlands 'the Netherlands
      Pharmacovigilance Foundation Lareb' maintains such a system. A primary aim in
      pharmacovigilance is the timely detection of either new ADRs or a change of the
      frequency of ADRs that are already known to be associated with the drugs
      involved, i.e. signal detection. Adequate signal detection solely based on the
      human intellect (case by case analysis or qualitative signal detection) is
      becoming time consuming given the increasingly large number of data, as well as
      less effective, especially in more complex associations such as drug-drug
      interactions, syndromes and when various covariates are involved. In quantitative
      signal detection measures that express the extent in which combinations of
      drug(s) and clinical event(s) are disproportionately present in the database of
      reported suspected ADRs are used to reveal associations of interest. Although the
      rationale and the methodology of the various quantitative approaches differ, they
      all share the characteristic that they express to what extent the number of
      observed cases differs from the number of expected cases. In this paper three
      Dutch examples are described in which a measure of disproportionality is used in
      quantitative signal detection in pharmacovigilance: (i) the association between
      antidepressant drugs and the occurrence of non-puerpural lactation as an example
      of an association between a single drug and a single event; (ii) the onset or
      worsening of congestive heart failure associated with the combined use of
      nonsteroidal anti-inflammatory drugs and diuretics as an example of an
      association between two drugs and a single event (drug-drug interaction); and the
      (iii) (co)-occurrence of fever, urticaria and arthralgia and the use of
      terbinafine as an example of an association between a single drug and multiple
      events (syndrome). We conclude that the use of quantitative measures in addition
      to qualitative analysis is a step forward in signal detection in
      pharmacovigilance. More research is necessary into the performance of these
      approaches, especially its predictive value, its robustness as well as into
      further extensions of the methodology.

PMID- 12071784
TI  - Signal selection and follow-up in pharmacovigilance.
AB  - The detection of unknown and unexpected connections between drug exposure and
      adverse events is one of the major challenges of pharmacovigilance. For the
      identification of possible connections in large databases, automated statistical
      systems have been introduced with promising results. From the large numbers of
      associations so produced, the human mind has to identify signals that are likely
      to be important, in need of further assessment and follow-up and that may require
      regulatory action. Such decisions are based on a variety of clinical,
      epidemiological, pharmacological and regulatory criteria. Likewise, there are a
      number of criteria that underlie the subsequent evaluation of such signals. A
      good understanding of the logic underlying these processes fosters rational
      pharmacovigilance and efficient drug regulation. In the future a combination of
      quantitative and qualitative criteria may be incorporated in automated signal
      detection.

PMID- 12071785
TI  - Causal association in pharmacovigilance and pharmacoepidemiology: thoughts on the
      application of the Austin Bradford-Hill criteria.
AB  - The methods used for the evaluation of drug safety signals (including major
      signals leading to withdrawal of products from the market) are inconsistent and
      sometimes of poor quality. While the assessment of the safety of medicines needs
      to consider specific issues such as drug interactions and variation in
      compliance, the general principles, which are used to study environmental
      hazards, can be applied for this purpose. The criteria proposed by Sir Austin
      Bradford-Hill more than 35 years ago for attributing disease causation to
      environmental factors have been used widely in epidemiology, are applicable to
      pharmacovigilance and pharmacoepidemiology. The Austin Bradford-Hill criteria
      include strength, consistency, specificity, temporality, biological gradient,
      plausibility, coherence, experimental evidence and analogy. The paper reviews
      each of these criteria with emphasis on pharmacovigilance and
      pharmacoepidemiology and with some examples. The application of the Austin
      Bradford-Hill criteria to the evaluation of causal association in
      pharmacovigilance and pharmacoepidemiology is very useful. However, it requires
      understanding of the limitations of the data, such as, under-reporting, poor
      quality of information from third parties and misclassification. Further work is
      required to develop strategies to handle these limitations.

PMID- 12071787
TI  - Facial clefting and psychiatric diseases: a follow-up of the Danish 1936-1987
      Facial Cleft cohort.
AB  - OBJECTIVE: This study assesses whether patients with facial cleft have an
      increased risk of psychiatric diseases. DESIGN: Through the Danish Facial Cleft
      Database, patients with facial cleft born between 1936 and 1987 in Denmark were
      identified, and the admission pattern for these patients with facial cleft was
      available for the period 1969 through 1993 through the Danish Psychiatric Central
      Registry. PARTICIPANTS: A total of 6,462 patients with facial cleft followed up
      for a total of 127,068 person-years. MAIN OUTCOME MEASURES Hospitalization for
      psychiatric diseases. The expected number of admissions for the cleft population
      was calculated by multiplication of the observed person-years with admission
      rates for Denmark stratified for sex, 1-year age group, and 1-year calendar
      period. RESULTS: A total of 284 patients with facial cleft (4.4%) were
      hospitalized for psychiatric diseases. The relative risk of hospitalization was
      1.65 (95% confidence interval 1.3 to 2.0) for patients with isolated cleft palate
      (CP) and 1.15 (95% confidence interval 0.99 to 1.29) for patients with cleft lip
      +/- cleft palate (CL[P]). The overall risk estimates were above unity for both CP
      and CL(P) in all major diagnosis groups, neurosis and autism (for CL[P]) being
      the only exceptions. The excess risk was not accounted for by patients with known
      associated anomalies/syndromes. CONCLUSION: The risk of hospitalized mental
      disorders in general is increased in patients with CP but not to any substantial
      degree in patients with CL(P). Both groups had an increased risk of mental
      retardation and substance abuse, but the risk for schizophrenia or bipolar
      illness was not statistically significantly increased, compared with the
      background population. Further, our data provide no evidence that the
      psychosocial stressors associated with CL(P) and its treatment have any
      substantial impact on the risk for hospitalized mental illness.

PMID- 12071786
TI  - A comparison of three methods of repairing the hard palate.
AB  - OBJECTIVE: To compare growth, speech, and nasal symmetry outcomes of three
      methods of hard palate repair. PATIENTS: Consecutive available records of
      children born with unilateral bony complete cleft lip and palate over the period
      1972 to 1992. INTERVENTIONS: Identical management of lip, nose, alveolus, and
      soft palate. Hard palate repair by Cuthbert Veau (CV) from 1972 to 1981, von
      Langenbeck (vL) from 1982 to 1989, or medial Langenbeck (ML) from 1989 to 1991.
      OUTCOME MEASURES: For growth: GOSLON yardstick or 5-year model index. For speech:
      articulation test. Nasal anemometry. For nasal symmetry: Coghlan computer-based
      assessment. All these measures were developed during the period of data
      collection but not for this project. RESULTS: There was a strong trend toward
      more favorable anteroposterior maxillary growth with the change from CV to vL to
      ML techniques. This fell short of statistical significance because of the small
      sample size. There was a significant reduction in cleft-related articulation
      faults (p =.01) considered to be related to improved arch form. In the absence of
      improved rates of velopharyngeal insufficiency or nasal symmetry, increased
      surgical experience was discounted as a significant contribution to improved
      growth and articulation outcomes. CONCLUSIONS: Reduced periosteal undermining and
      residual exposed palatal shelf from CV to vL to ML improved incisor relationships
      and articulation.

PMID- 12071788
TI  - Speech outcomes in isolated cleft palate: impact of cleft extent and additional
      malformations.
AB  - OBJECTIVE: The purpose of the study was to study the speech outcome in a series
      of 5-year-old children born with an isolated cleft palate and compare the speech
      with that of noncleft children and to study the impact of cleft extent and
      additional malformation on the speech outcome. DESIGN: A cross-sectional
      retrospective study. SETTING: A university hospital serving a population of 1.5
      million inhabitants. SUBJECTS: Fifty-one patients with an isolated cleft palate;
      22 of these had additional malformations. Thirteen noncleft children served as a
      reference group. INTERVENTIONS: A primary soft palate repair at a mean of 8
      months of age and a hard palate closure at a mean age of 4 years and 2 months if
      the cleft extended into the hard palate. MAIN OUTCOME MEASURES: Perceptual
      judgment of seven speech variables assessed on a five-point scale by three
      experienced speech pathologists. RESULTS: The cleft palate group had
      significantly higher frequency of speech symptoms related to velopharyngeal
      function than the reference group. There were, however, no significant
      differences in speech outcome between the subgroup with a nonsyndromic cleft and
      the reference group. Cleft extent had a significant impact on the variable
      retracted oral articulation while the presence of additional malformations had a
      significant impact on several variables related to velopharyngeal function and
      articulation errors. CONCLUSION: Children with a cleft in the soft palate only,
      with no additional malformations, had satisfactory speech, while children with a
      cleft palate accompanied by additional malformations or as a part of a syndrome
      should be considered to be at risk for speech problems.

PMID- 12071789
TI  - Perceptual evaluation of speech and velopharyngeal function in children with and
      without cleft palate and the relationship to nasal airflow patterns.
AB  - OBJECTIVES: The aim was to study the relationship between perceptual evaluation
      of speech variables related to velopharyngeal function and the pattern of nasal
      airflow during the velopharyngeal closing phase in speech in children with and
      without cleft palate. PARTICIPANTS: Fourteen children with cleft lip and palate
      or cleft palate only and 15 controls aged 7 and 10 years. All were native Swedish
      speakers. METHOD: Three experienced listeners performed a blinded perceptual
      speech evaluation. Nasal airflow was transduced with a pneumotachograph attached
      to a nasal mask. The duration from peak to 5% nasal airflow, maximum flow
      declination rate, and nasal airflow at selected points in time during the
      transition from nasal to stop consonants in bilabial and velar articulatory
      positions in sentences were estimated. The analysis was focused on the perceptual
      ratings of "velopharyngeal function" and "hypernasality." RESULTS: A strong
      association was found between ratings of "velopharyngeal function" and
      "hypernasality" and the pattern of nasal airflow during the bilabial nasal-to
      stop combination /mp/. Both the sensitivity and specificity were 1.00 for the
      bilabial temporal airflow measure in relation to ratings of "velopharyngeal
      function." The nasal airflow rate during /p/ in /mp/ had a sensitivity of 1.00
      and specificity of 0.92 to 0.96 in relation to ratings of "hypernasality."
      CONCLUSION: Assessment of the nasal airflow dynamics during the velopharyngeal
      closing phase in speech presents quantitative, objective data that appear to
      distinguish between perceptually normal and deviant velopharyngeal function with
      high sensitivity and specificity.

PMID- 12071790
TI  - Constriction of the maxillary dental arch by mucoperiosteal denudation of the
      palate.
AB  - OBJECTIVE: This study examined the influence of two factors in the constriction
      of the maxillary dental arch by mucoperiosteal denudation of the palate: (1)
      inhibition of lateral growth and (2) medial inclination of teeth. METHOD: Thirty
      five male 20-day-old Wistar rats were divided into experimental and control
      groups. The experimental group had bilateral mucoperiosteum excised in the
      lateral one third of the palate. Methyl methacrylate resin-embedded frontal
      sections were prepared from both groups after alternate weekly injections of
      tetracycline and calcein in the dorsal subcutaneous area. The sections were
      observed and photographed under either a confocal laser scanning microscope, a
      fluorescence microscope, or both. Chronological changes in lateral palatal
      growth, maxillary dental arch width, and inclination of the upper first molars
      were examined up to 8 weeks after the operation. Paraffin-embedded frontal
      sections were also made and stained with Elastica van Gieson stain. RESULTS: The
      scar tissue formed on the rat palate by the mucoperiosteal denudation was tightly
      connected to the palatal bone and teeth. The intervals between the labeling lines
      of the experimental group were less definite during the first 2 weeks after the
      operation. Increments of palatal and maxillary dental arch widths were smaller in
      the experimental group than in the control group. The upper first molars in the
      control group gradually inclined laterally, whereas those in the experimental
      group inclined medially with age. CONCLUSION: Medial inclination of teeth is a
      stronger influence than inhibition of lateral growth on constriction of the rat
      maxillary dental arch.

PMID- 12071791
TI  - Temporal characteristics of aerodynamic segments in the speech of children and
      adults.
AB  - OBJECTIVES: The primary purpose of this study was to determine the temporal
      characteristics of aerodynamic segments in the normal speech of children and
      adults without cleft palate. A secondary objective was to determine the within
      speaker variability of the segments. METHOD: Speakers consisted of 46 children
      aged 6 to 8 years, 41 older children aged 11 to 12 years, and 41 adults aged 18
      to 37 years (total n = 128) who repeated the word "hamper" during continuous
      utterances. The pressure-flow method was used to determine the duration of six
      segments of the oral air pressure and nasal airflow pulses associated with the
      /mp/ sequence. Descriptive statistics, including coefficients of variation (COV),
      were computed for each segment as a function of age and sex of the speakers.
      Analysis of variance (ANOVA) procedures were used to determine the effects of
      age, sex, or both on the temporal variables. RESULTS: ANOVAs indicated
      statistically significant main effects (p <.008) for age on five of the six
      temporal measures and for sex on three of the six measures. Five of the six COVs
      were also statistically significant for age. There were no statistically
      significant interactions between speaker age and sex for any measure.
      CONCLUSIONS: The results indicate distinct patterns of timing for aerodynamic
      segments of speech produced by children and adults. Overall, adults exhibited
      less temporal variability than children. The generally longer and more variable
      segments produced by children suggest diagnostic and treatment implications
      relative to speakers with velopharyngeal dysfunction.

PMID- 12071792
TI  - A histological study on experimental tooth movement into bone induced by
      recombinant human bone morphogenetic protein-2 in beagle dogs.
AB  - OBJECTIVE: The purpose of this preliminary study was to examine experimental
      tooth movement into newly generated bone induced by recombinant human bone
      morphogenetic protein-2 (rhBMP-2). METHOD: After extraction of the maxillary
      first premolars, bone defects were surgically created in eight adult beagle dogs
      using a 5-mm-diameter trepan bar. According to which material was grafted into
      the bone defects, animals were divided into the following four groups: (1) the
      rhBMP-2 group in which rhBMP-2 with a poly[ D,L-(lactide-co-glycolide)]/gelatin
      sponge complex was implanted; (2) the spongiosa group in which spongiosa from the
      tibia was grafted; (3) the nongrafted group in which no material was embedded;
      and (4) the control group in which only tooth extraction was performed. The
      osteoinductive activity of rhBMP-2 and tooth movement into the newly generated
      bone were examined by histological and morphometric comparisons of each group.
      RESULTS: Considerable new bone formation was observed at the grafted site both in
      the rhBMP-2 and in the spongiosa groups. The area of generated bone in the rhBMP
      2 group was significantly greater than that in the spongiosa group. Newly
      generated bone, in both the rhBMP-2 and spongisosa groups, showed a similar
      histological response to orthodontic force as in normal alveolar bone in the
      control group. However, root resorption occurred on the pressure side in the
      rhBMP-2 group. CONCLUSION: These results indicated that rhBMP-2 might constitute
      an alternative material to autogeneous bone grafting for alveolar cleft defects.
      Further studies regarding tooth movement into generated bone induced by rhBMP-2
      are suggested.

PMID- 12071793
TI  - Tooth eruption into the newly generated bone induced by recombinant human bone
      morphogenetic protein-2.
AB  - OBJECTIVE: The purpose of this study was to observe tooth eruption pattern into
      the newly generated bone induced by recombinant human bone morphogenetic protein
      2 (rhBMP-2). METHOD: Three 12-week-old beagle dogs were used. Following wound
      healing of the extracted maxillary third deciduous incisor at the age of 13
      weeks, a resection of maxillary alveolar bone (8 mm by 8 mm by 8 mm) was carried
      out, accompanied by extraction of the maxillary second incisor tooth germ. The
      rhBMP-2 (5 microgram/100 microL or 10 microgram/100 microL) was implanted in the
      resected area. A group that was not implanted after resection and a nonresected
      group were used as controls. Serial changes of the eruption pattern of the
      maxillary third incisor in the implanted area were observed radiographically.
      Oxytetracycline and calcein were employed as bone markers. Nine weeks after the
      implantation, the animals were sacrificed. The samples were observed
      histologically and analyzed using peripheral quantitative computerized tomography
      to acquire the bone mineral density (BMD). RESULTS: In the rhBMP-2 (5
      microgram/100 microL)-treated group, histological findings and the BMD of the
      newly generated bone were almost same as in the nonresected group. The maxillary
      third incisor erupted through the implanted area. However, in the rhBMP-2 (10
      microgram/100 microL)-treated group, more osteoinductive activity and
      significantly higher BMD were observed in the newly generated bone. The maxillary
      third incisor erupted mesially so as to avoid this implanted area. CONCLUSION:
      Results showed that bone remodeling and tooth eruption through the newly
      generated bone appear to be dose dependent. Accordingly, proper dosage of rhBMP-2
      should be determined for successful clinical application.

PMID- 12071794
TI  - Upper lip fistulas: three new cases.
AB  - OBJECTIVE: We present three new cases of congenital upper lip fistula. Two of
      them were located in the philtrum midline, one of which was associated to a
      double maxillary frenulum, a medial lip cleft, and a medial cleft of the
      primitive palate. The other was located in the left side of the vermilion. All
      three patients had clear fluid discharge through the fistulous orifice without
      pain. Two of them had a history of recurrent swelling of the philtrum area.
      CONCLUSIONS: A simple surgical excision is the treatment of choice in these
      cases, in which the anatomy is preserved; this fact is more consistent with a
      completed but aberrant development than with focal dysgenesis.

PMID- 12071795
TI  - Gross unilateral abnormalities of the velum and pharynx.
AB  - OBJECTIVE: Velopharyngeal incompetence because of gross unilateral velopharyngeal
      hypoplasia is rare, particularly in patients with no significant hemifacial
      microsomia or facial asymmetry. We describe the abnormal anatomy and treatment of
      three patients with gross congenital velopharyngeal asymmetry. RESULTS AND
      CONCLUSIONS: Following surgery, all three patients showed a good improvement in
      velopharyngeal function and speech. Nasendoscopy and lateral videofluoroscopy
      were important in confirming the abnormal anatomy and pathology and in evaluating
      the degree of movement of the affected side of the velum and pharyngeal walls as
      well as the size and location of the defect. Muscles from the normal side were
      radically dissected and mobilized across the midline to reconstruct the
      hypoplastic hemivelum. Mucosal lengthening was achieved by suturing the normal
      mucosa to the mucosa of the hypoplastic hemivelum and the lateral pharyngeal wall
      or by insetting a posterolateral pharyngeal flap (modified Moore pharyngoplasty)
      into the nasal surface of the hypoplastic side.

PMID- 12071796
TI  - Extensive facial clefting in a patient with Goltz syndrome: multidisciplinary
      treatment of a previously unreported association.
AB  - OBJECTIVE: Goltz syndrome is a rare, X-linked dominant, multisystem disorder
      found almost exclusively in female patients. Although the cutaneous features
      predominate in most reports, characteristic abnormalities are also frequently
      present in the musculoskeletal system and facial region. We report a female
      infant born with a severe form of Goltz syndrome that included an extremely wide
      facial cleft, an abnormality not previously reported in a patient with this
      disorder. Her management demonstrates the advantages of a multidisciplinary
      approach to effectively care for patients with severe craniofacial abnormalities.

PMID- 12071797
TI  - An alternative, simple device for preventing obstruction of the endotracheal
      tube.

PMID- 12071798
TI  - Radiation research society 1952-2002. Physics as an element of radiation
      research.
AB  - Since its inception in 1954, Radiation Research has published an estimated total
      of about 8700 scientific articles up to August 2001, about 520, or roughly 6%, of
      which are primarily related to physics. This average of about 11 articles per
      year indicates steadily continuing contributions by physicists, though there are
      appreciable fluctuations from year to year. These works of physicists concern
      radiation sources, dosimetry, instrumentation for measurements of radiation
      effects, fundamentals of radiation physics, mechanisms of radiation actions, and
      applications. In this review, we have selected some notable accomplishments for
      discussion and present an outlook for the future.

PMID- 12071799
TI  - Electron spectra and the RBE of X rays.
AB  - For an assessment of the possible difference in effectiveness between mammography
      X rays and conventional X rays, the energy and LET spectra of the released
      electrons are examined. At photon energies below 20 keV and above 100 keV, the
      energy of the electrons increases with increasing photon energy, which implies
      that higher-energy photons produce less densely ionizing radiation and are
      therefore somewhat less effective per unit dose. However, in the intermediate
      energy range from 20 keV to 100 keV-the range that is relevant to medical
      diagnostics-the change from the photoelectric effect to the Compton effect causes
      a transient decrease of electron energies. The ionization density is therefore
      similar for 200 kVp X rays and 30 kVp mammography X rays, and the distributions
      of dose in LET suggest an RBE of 30 kVp mammography X rays compared to 200 kVp X
      rays of up to 1.3. This is in line with an earlier assessment by Brenner and
      Amols in terms of microdosimetric data, but it is strongly at variance with a
      recent claim that X rays for mammography are about four times more effective at
      small doses than conventional X rays and that they cause a correspondingly
      greater risk for breast cancer. Since LET need not be the only relevant factor,
      general response functions are examined here that specify-at low dose-the effect
      per electron of initial energy E and account, for example, for a particular role
      of the electron range. It is shown that, with any response per electron track
      that is a nondecreasing function of its starting energy, the low-dose RBE of the
      mammography X rays relative to the 200 kVp X rays must be substantially less than
      2. The Auger electron that accompanies most photoelectrons, but only a minority
      of the Compton electrons, may increase the effectiveness of the mammography X
      rays somewhat, but it cannot explain the reported high values of the RBE.

PMID- 12071800
TI  - Alteration of protein structure induced by low-energy (<18 eV) electrons. I. The
      peptide and disulfide bridges.
AB  - We present measurements of low-energy (<18 eV) electron-stimulated desorption of
      anions from acetamide (CH(3)CONH(2)) and dimethyl disulfide [DMDS: (CH(3)S)(2)]
      films. Electron irradiation of physisorbed CH(3)CONH(2) produces H(-), CH(3)(-)
      and O(-) anions, whereas the H(-), CH(2)(-), CH(3)(-), S(-), SH(-) and SCH(3)(-)
      anions are observed to desorb from the DMDS film. Below 12 eV, the dependence of
      the anion yields on the incident electron energy exhibits structures that
      indicate that a resonant process (i.e. dissociative electron attachment) is
      responsible for molecular fragmentation. Within the range of 1-18 eV, it is found
      that (1.7 and 1.4) x 10(7) H(-) ions/incident electron and (7.8 x 10(-11) and 4.3
      x 10(-8)) of the other ions/incident electron are desorbed from acetamide and
      DMDS films, respectively. These results suggest that, within proteins, the
      disulfide bond is more sensitive to low-energy electron attack than the peptide
      bond. In biological cells, some proteins interact closely with nucleic acid.
      Therefore, the observed fragments, when produced from secondary low-energy
      electrons generated by high-energy radiation, not only may denature proteins, but
      may also induce reactions with the nearby nucleic acid and damage DNA.

PMID- 12071802
TI  - Dose responses for chromosome aberrations produced in noncycling primary human
      fibroblasts by alpha particles, and by gamma rays delivered at sublimiting low
      dose rates.
AB  - As the total dose of X or gamma rays is delivered at lower and lower rates, the
      yield of chromosome aberrations progressively diminishes. Simultaneously, the
      shape of the dose response changes from one exhibiting pronounced upward
      curvature at high dose rates to one approaching linearity at low dose rates.
      Although the maximum sparing effect caused by lowering the dose rate can be
      predicted from classical cytogenetic theory, it has yet to be verified
      experimentally. Here, noncycling normal human fibroblasts were exposed to graded
      doses of (137)Cs gamma rays at chronic dose rates of 6.3 and 2.8 cGy h(-1), dose
      rates that we reasoned should be lower than those required to achieve maximal
      sparing. This was indeed shown to be the case, after it was determined that the
      two chronic dose rates produced identical linear dose responses of 0.05 total
      aberrations per cell Gy(-1). Consistent with cytogenetic theory, this value was
      statistically indistinguishable from the linear coefficient derived from a fit to
      aberration frequencies produced by high-dose-rate exposure. Exposure to (238)Pu
      alpha particles also produced a linear dose response for total aberrations, whose
      slope-with respect to (137)Cs gamma rays as a reference radiation-implied a
      maximum RBE of 35 +/- 2.

PMID- 12071801
TI  - Spatial distribution and yield of DNA double-strand breaks induced by 3-7 MeV
      helium ions in human fibroblasts.
AB  - Accelerated helium ions with mean energies at the target location of 3-7 MeV were
      used to simulate alpha-particle radiation from radon daughters. The experimental
      setup and calibration procedure allowed determination of the helium-ion energy
      distribution and dose in the nuclei of irradiated cells. Using this system, the
      induction of DNA double-strand breaks and their spatial distributions along DNA
      were studied in irradiated human fibroblasts. It was found that the apparent
      number of double-strand breaks as measured by a standard pulsed-field gel assay
      (FAR assay) decreased with increasing LET in the range 67-120 keV/microm
      (corresponding to the energy of 7-3 MeV). On the other hand, the generation of
      small and intermediate-size DNA fragments (0.1-100 kbp) increased with LET,
      indicating an increased intratrack long-range clustering of breaks. The fragment
      size distribution was measured in several size classes down to the smallest class
      of 0.1-2 kbp. When the clustering was taken into account, the actual number of
      DNA double-strand breaks (separated by at least 0.1 kbp) could be calculated and
      was found to be in the range 0.010-0.012 breaks/Mbp Gy(-1). This is two- to
      threefold higher than the apparent yield obtained by the FAR assay. The measured
      yield of double-strand breaks as a function of LET is compared with theoretical
      Monte Carlo calculations that simulate the track structure of energy depositions
      from helium ions as they interact with the 30-nm chromatin fiber. When the
      calculation is performed to include fragments larger than 0.1 kbp (to correspond
      to the experimental measurements), there is good agreement between experiment and
      theory.

PMID- 12071803
TI  - Microdistribution of alpha particles in pathological sections of tissues from
      thorotrast patients detected by imaging plate autoradiography.
AB  - Thorotrast is a colloidal suspension of radioactive (232)ThO(2) that naturally
      emits alpha particles (90%), beta particles and gamma rays (10%). Thorotrast was
      used as a radiographic contrast agent in the 1930s-1950s; it caused liver cancer
      several decades after injection because of its life-long deposition and exposure.
      Determination of the amount and the distribution of radioactive thorium are
      essential for assessment of radiation risks. We visualized alpha particles on
      ordinary archival tissue sections using an imaging plate and a BAS5000 image
      analyzer. Furthermore, we confirmed that the imaging system is sensitive enough
      to detect alpha particles and accurate in measuring the total amount of thorium
      deposited in the organ from a single tissue section. This method revealed that
      the amount of thorium deposited in tumor tissue is correlated to that in non
      tumor tissue. Thorotrast deposition was not associated with DNA damage determined
      by histochemistry. In combination with histological findings, it is suggested
      that radioactive thorium always migrates within the deposited organs by
      macrophages, and that the organs are evenly exposed to alpha particles.

PMID- 12071804
TI  - Solid cancer risk coefficient for fast neutrons in terms of effective dose.
AB  - Cancer mortality risk coefficients for neutrons have recently been assessed by a
      procedure that postulates for the neutrons a linear dose dependence, invokes the
      excess risk of the A-bomb survivors at a gamma-ray dose D(1) of 1 Gy, and assumes
      a neutron RBE as a function of D(1) between 20 and 50. The excess relative risk
      (ERR) of 0.008/mGy has been obtained for R(1) = 20 and 0.016/mGy for R(1) = 50.
      To compare these results to the current ICRP nominal risk coefficient for solid
      cancer mortality (0.045/Sv for a population of all ages; 0.036/Sv for a working
      population), the ERR is translated into lifetime attributable risk and is then
      related to effective dose. The conversion is not trivial, because the neutron
      effective dose has been defined by ICRP not as a weighted genuine neutron dose
      (neutron kerma), but as a weighted dose that includes the dose from gamma rays
      that are induced by neutrons in the body. If this is accounted for, the solid
      cancer mortality risk for a working population is found to agree with the ICRP
      nominal risk coefficient for neutrons in their most effective energy range, 0.2
      MeV to 0.5 MeV. In radiation protection practice, there is an added level of
      safety, because the effective dose, E, is-for monitoring purposes-assessed in
      terms of the operational quantity H*, which overestimates E substantially for
      neutrons between 0.01 MeV and 2 MeV.

PMID- 12071805
TI  - Cytogenetic analysis of radiation-induced leukemia in Trp53-deficient C3H/He
      mice.
AB  - C3H/He mice develop acute myeloid leukemia (AML) after whole-body irradiation,
      but the strain becomes highly susceptible to stem cell leukemia (SCL) when a null
      mutation is introduced into the Trp53 gene. To examine the etiology of SCL and
      the influence of chromosomal instability on leukemogenesis, 12 SCLs and two AMLs
      arising from Trp53-deficient C3H/He mice were investigated cytogenetically. Each
      SCL demonstrated cell-to-cell variation in the number and structural integrity of
      their chromosomes, indicating chromosomal instability. Typical deletion of
      chromosome 2 was observed in the two AML cases, while most SCL cells did not
      display this aberration. Deletions and rearrangements of chromosome 11 were
      noticeable in SCLs from Trp53 heterozygotes but not in AMLs. Analysis of loss of
      heterozygosity revealed that aberrations involving chromosome 11 in SCLs resulted
      in loss of the wild-type Trp53 allele. These results suggest that loss of Trp53
      function triggers the tumorigenic process leading toward SCL through the
      induction of chromosomal instability, and that SCL and AML are distinct varieties
      of leukemia.

PMID- 12071806
TI  - The genetic control of chemically and radiation-induced skin tumorigenesis: a
      study with carcinogenesis-susceptible and carcinogenesis-resistant mice.
AB  - Outbred carcinogenesis-resistant (Car-R) and carcinogenesis-susceptible (Car-S)
      mouse lines were generated by phenotypic selection for resistance or
      susceptibility to two-stage skin carcinogenesis. These two Car mouse lines differ
      by >100-fold in susceptibility. In the present study, we tested the hypothesis
      that a subset of genetic loci responsible for susceptibility or resistance to
      chemical skin tumorigenesis may also be involved in radiation-induced skin
      tumorigenesis. Skin tumorigenesis was tested in groups of Car-S/R mice after X
      ray initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. We found
      that ionizing radiation can initiate skin tumors in Car-S mice but not in Car-R
      mice. In Car-S mice, the most effective radiation doses (6 and 10 Gy given in
      four fractions) gave a threefold increase in tumor multiplicity and a twofold
      increase in tumor incidence compared to a TPA-only control group. We performed a
      molecular analysis of Hras gene mutations in skin tumors of Car-S mice induced by
      X-ray initiation/TPA promotion or by TPA promotion alone. The most notable
      difference emerging from the comparison of these mutation patterns is the high
      incidence ( approximately 50%) of papillomas lacking Hras gene mutations in X-ray
      initiated/TPA-promoted papillomas compared to 13% in papillomas induced by TPA
      alone, suggesting that lack of Hras gene mutations is a consistent feature of
      radiation-induced papillomas.

PMID- 12071807
TI  - 7-Hydroxystaurosporine (UCN-01) preferentially sensitizes cells with a disrupted
      TP53 to gamma radiation in lung cancer cell lines.
AB  - Mutations in TP53 occur in more than 50% of the lung cancer patients and are
      associated with an increased resistance to chemotherapy and radiotherapy. The
      human lung adenocarcinoma cell lines A549 and LXSN contain a wild-type TP53 and
      were growth arrested at both the G(1)- and G(2)-phase checkpoints after
      irradiation. However, a TP53-disrupted cell line, E6, was arrested only at the
      G(2)-phase checkpoint. UCN-01 (7-hydroxystaurosporine), a CHEK1 inhibitor that
      abrogates the G(2) block, has been reported to enhance radiation toxicity in
      human lymphoma and colon cancer cell lines. In this study, UCN-01 preferentially
      enhanced the radiosensitivity of the TP53-disrupted E6 cells compared to the TP53
      wild-type cells. This effect was more pronounced in cells synchronized in early
      G(1) phase, where the E6 cells showed a higher resistance to radiation in the
      absence of drug. These results indicate that the combination of UCN-01 and
      radiation can more specifically target resistant TP53 mutated cancer cells and
      spare TP53 wild-type normal cells.

PMID- 12071808
TI  - Carbogen breathing after irradiation enhances the effectiveness of tirapazamine
      in SiHa tumors but not SCCVII tumors in mice.
AB  - The penetration of anticancer agents into tumor tissue has recently attracted
      considerable attention. This study examines the effect of carbogen breathing on
      the antitumor activity of tirapazamine combined with radiation. Our hypothesis is
      based on the observation that the diffusion of tirapazamine through tissue is
      dependent on oxygen tension. We postulated that carbogen breathing might enhance
      the ability of tirapazamine to diffuse to hypoxic cells located distal to
      functional blood vessels in tumors. We first determined that carbogen breathing
      caused no significant change in the pharmacokinetics of tirapazamine, suggesting
      that any effect of carbogen breathing on the activity of tirapazamine is not
      attributable to modulation of pharmacokinetics. Cell survival in SCCVII and SiHa
      tumors after 10 Gy X rays alone was similar. However, when tirapazamine was
      administered 30 min after radiation treatment under air-breathing conditions,
      cell killing was greater in SCCVII tumors compared to SiHa tumors. Carbogen
      breathing during the exposure to tirapazamine did not change the cell survival in
      SCCVII tumors, but it enhanced cell killing in the SiHa tumors. Interestingly,
      carbogen breathing during radiation treatment produced greater cell killing in
      the SiHa tumors than in the SCCVII tumors. The vascular architecture and type of
      hypoxia in the two tumors probably underlie the differences in the responses of
      the two tumors. These findings suggest that the effectiveness of tirapazamine and
      other hypoxic cytotoxins may be dependent on tumor type.

PMID- 12071809
TI  - Delayed cytoprotection after enhancement of Sod2 (MnSOD) gene expression in SA-NH
      mouse sarcoma cells exposed to WR-1065, the active metabolite of amifostine.
AB  - SA-NH mouse sarcoma cells were grown to confluence and then exposed to either 40
      microM or 4 mM of WR-1065, i.e. the active thiol form of amifostine, for 30 min
      and then washed. Total RNA and protein were isolated at various times up to 24 h
      after exposure. Both concentrations of WR-1065 were equally effective in
      affecting Sod2 (also known as MnSOD) gene expression and protein levels. Northern
      blot analysis using a mouse cDNA probe revealed three Sod2 transcripts of 1, 4
      and 6 kb. Expression of both the 4- and 6-kb transcripts increased by 20 and 60%,
      respectively, and remained elevated over a period of 4 to 20 h. Sod2 protein
      levels, as determined by Western blot analysis, increased 15-fold over background
      control levels over the same interval. Sod2 protein was evaluated using activity
      gels and was found to be active. SA-NH cells were irradiated with X rays either
      in the presence of 40 microM or 4 mM WR-1065 or 24 h later after its removal,
      when Sod2 protein levels were most elevated. No protection was observed for cells
      irradiated in the presence of 40 microM WR-1065. In contrast, survival after a
      dose of 2 Gy was elevated 1.27-, 1.14- and 1.20-fold in SA-NH cells irradiated in
      the presence of 4 mM WR-1065 or 24 h after exposure of the cells to 40 microM and
      4 mM WR-1065, respectively. The increased survival levels observed 24 h after
      exposure to WR-1065 represents a delayed radioprotective effect of WR-1065 and
      corresponds to the time at which Sod2 protein levels are most elevated. These
      data demonstrate a novel mechanism for radioprotection by WR-1065 and suggest a
      new potential concern regarding the issue of tumor protection.

PMID- 12071810
TI  - Antimutagenicity of WR-1065 in L5178Y cells exposed to accelerated (56)Fe ions.
AB  - The ability of the aminothiol WR-1065 [N-(2-mercaptoethyl)-1,3-diaminopropane] to
      protect L5178Y (LY) cells against the cytotoxic and mutagenic effects of exposure
      to accelerated (56)Fe ions (1.08 GeV/nucleon) was determined. It was found that
      while WR-1065 reduced the mutagenicity in both cell lines when it was present
      during the irradiation, the addition of WR-1065 after the exposure had no effect
      on the mutagenicity of the radiation in either cell line. No marked protection
      against the cytotoxic effects of exposure to (56)Fe ions was provided by WR-1065
      when added either during or after irradiation in either cell line. We reported
      previously that WR-1065 protected the LY-S1 and LY-SR1 cell lines against both
      the cytotoxicity and mutagenicity of X radiation when present during exposure,
      but that its protection when administered after exposure was limited to the
      mutagenic effects in the radiation-hypersensitive cell line, LY-S1. The results
      indicate that the mechanisms involved differ in the protection against cytotoxic
      compared to mutagenic effects and in the protection against damage caused by
      accelerated (56)Fe ions compared to X radiation.

PMID- 12071811
TI  - Intensity-modulated radiation therapy.
AB  - Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical
      means of tightly focusing the radiation dose around a cancer. As with
      stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on
      the target. The potential for total dose escalation and for escalation of daily
      fraction size to the gross cancer is exciting. The excitement, however, has
      greatly overshadowed a range of radiobiological and clinical concerns.

PMID- 12071812
TI  - Report on an interagency workshop on the radiobiology of nuclear terrorism.
      Molecular and cellular biology dose (1-10 Sv) radiation and potential mechanisms
      of radiation protection (Bethesda, Maryland, December 17-18, 2001).
AB  - The events of September 11, 2001 have focused attention on the possibility of
      nuclear terrorism, and 1-10 Sv is arguably the dose range of biological interest,
      since doses in this range both pose a risk of acute effects and are potentially
      survivable. Because of this interest, a coalition of U.S. government agencies
      (NCI, DOD, DOE) and the Radiation Research Society convened a workshop in
      December 2001 "to focus on molecular, cellular and tissue changes that occur [at
      doses of 1-10 Sv] and potential mechanisms of radioprotection". A draft report of
      this workshop was posted on the NCI website in February 2002. According to the
      draft, the workshop was also intended to "determine the research opportunities
      and resources required [and] develop a research-action plan for further
      discussion and implementation." Injuries after exposure to ionizing radiation are
      important to patients with cancer and to populations potentially subject to
      accidental or intentional exposure. In these populations, partial- or whole-body
      exposures in the range of 1-10 Sv are possible. The consequences of exposure of
      limited tissue volumes to doses above 10 Sv have been researched because of their
      applicability to cancer therapy, while exposure to doses below 1 Sv has been
      researched because of nuclear fallout and space exploration issues. Except for
      research aimed at protection of members of the armed forces, the intervening dose
      range has received relatively little attention. The workshop participants
      concluded that although we currently have only a limited ability to deal with the
      consequences of radiation exposures in this range, focused research would have
      the potential of rapidly expanding such capabilities.

PMID- 12071813
TI  - Infantile hemangioma: clinical resolution with 5% imiquimod cream.

PMID- 12071816
TI  - Necrotizing fasciitis: report of 39 pediatric cases.
AB  - BACKGROUND: Necrotizing fasciitis (NF) is a severe, life-threatening soft tissue
      infection. General features and risk factors for fatal outcome in children are
      not well known. OBJECTIVE: To characterize the features of NF in children and the
      risk factors for fatal outcome. DESIGN: Retrospective, comparative,
      observational, and longitudinal trial. SETTING: Dermatology department of a
      tertiary care pediatric hospital. PATIENTS: All patients with clinical and/or
      histopathological diagnosis of NF seen from January 1, 1971, through December 31,
      2000. MAIN OUTCOME VARIABLES: Incidence, age, sex, number and location of
      lesions, preexisting conditions, initiating factors, clinical and laboratory
      features, diagnosis at admission, treatment, evolution, sequelae, and risk
      factors for fatal outcome. RESULTS: We examined 39 patients with NF (0.018% of
      all hospitalized patients). Twenty-one patients (54%) were boys. Mean age was 4.4
      years. Single lesions were seen in 30 (77%) of patients, with 21(54%) in
      extremities. The most frequent preexisting condition was malnutrition in 14
      patients (36%). The most frequent initiating factor was varicella in 13 patients
      (33%). Diagnosis of NF at admission was made in 11 patients (28%). Bacterial
      isolations in 24 patients (62%) were polymicrobial in 17 (71%). Pseudomonas
      aeruginosa was the most frequently isolated bacteria; gram-negative isolates, the
      most frequently associated bacteria. Complications were present in 33 patients
      (85%), mortality in 7 (18%), and sequelae in 29 (91%) of 32 surviving patients.
      The significant risk factor related to a fatal outcome was immunosuppression.
      CONCLUSIONS: Necrotizing fasciitis in children is frequently misdiagnosed, and
      several features differ from those of NF in adults. Immunosuppression was the
      main factor related to death. Early surgical debridement and antibiotics were the
      most important therapeutic measures.

PMID- 12071815
TI  - Routine vs extensive malignancy search for adult dermatomyositis and
      polymyositis: a study of 40 patients.
AB  - OBJECTIVE: To identify potential risk factors and the yield of routine screens
      for early detection of malignancy associated with dermatomyositis (DM) and
      polymyositis (PM). DESIGN: Retrospective study of malignancies in all patients
      with DM or PM followed up between the years 1981 and 2000 and a review of the
      relationship of DM and PM to malignancy, the usefulness of various tests or
      examinations for malignancy search, and the patients' course. SETTING:
      Departments of internal medicine and dermatology in a teaching hospital.
      PATIENTS: Forty consecutive adult patients with DM (33 cases) or PM (7 cases).
      MAIN OUTCOME MEASURES: (1) Rate of false-negative results of routine workup and
      yield (percentage of positive results) of blind malignancy search and (2)
      comparison of 16 characteristics in patients with malignancy vs those without.
      RESULTS: Malignancy occurred in 16 patients: 13 with DM and 3 with PM. In all
      cases, the diagnosis of malignancy was made concurrently with or shortly after
      the diagnosis of DM or PM. Factors associated with malignancy were recruitment in
      the internal medicine department (P =.02), constitutional symptoms (P<.01), a
      rapid onset of DM or PM (P =.02), the lack of Raynaud phenomenon (P<.01), and a
      higher mean erythrocyte sedimentation rate (P<.01) and creatine kinase level
      (P<.01). Initial routine search failed to discover 4 malignancies, 3 of which
      were discovered at an advanced stage by more extensive investigations. The
      positive result yield of blind malignancy search was only 13% (11 of 87), but
      reached 28% (5 of 18) for blind abdominal-pelvic and thoracic computed
      tomographic scans. CONCLUSION: Extensive search for malignancy, particularly
      computed tomographic scans, may be warranted in at least a subset of patients
      with DM or PM and risk factors of malignancy.

PMID- 12071817
TI  - Risk factors for lethal outcome in patients with bullous pemphigoid: low serum
      albumin level, high dosage of glucocorticosteroids, and old age.
AB  - BACKGROUND: Although bullous pemphigoid (BP) is the most frequent autoimmune
      bullous disease and is associated with a considerable case-fatality rate, little
      is known about factors that influence its prognosis. OBJECTIVE: To identify
      prognostic factors for lethal outcome in the first year after the initial
      hospitalization in patients with BP. DESIGN: A multicenter retrospective cohort
      study. SETTING: Seven dermatologic university hospitals in Germany. PARTICIPANTS:
      A total of 369 patients diagnosed as having BP between January 1, 1987, and
      December 31, 1997. STATISTICS: Univariate (Kaplan-Meier) and multivariate (Cox
      regression) analysis. RESULTS: Of the 369 patients with BP, 209 (57%) died, 106
      (29%) within the first year after hospitalization. Fifty-four percent were women.
      The mean +/- SD age at entry was 77.3 +/- 11.1 years. The patients with BP were
      followed up to 10.5 years, with a median time of 1.8 years to death or interview
      (25th and 75th quartiles, 0.5 and 4.0 years). The major risk factors for lethal
      outcome in the first year after hospitalization were an increased age, with a
      multivariate risk estimate of 3.2 (95% confidence interval [CI], 1.9-5.2) for age
      greater than 80.4 years (median); a daily glucocorticosteroid dosage of more than
      37 mg (75th quartile) at discharge, with a multivariate risk estimate of 2.5 (95%
      CI, 1.5-4.3); serum albumin levels of 3.6 g/dL or less (25th quartile), with a
      multivariate risk estimate of 2.6 (95% CI, 1.5-4.4); and an erythrocyte
      sedimentation rate greater than 30 mm/h (75th quartile), with a multivariate risk
      estimate of 1.7 (95% CI, 1.1-2.8). CONCLUSIONS: There is a considerable case
      fatality rate in patients with BP. Older patients who require a higher dosage of
      oral glucocorticosteroids at hospital discharge and who have low serum albumin
      levels are at greater risk of death within the first year after hospitalization.
      These prognostic factors should be considered in the care of patients with BP as
      well as in the design of future clinical trials.

PMID- 12071818
TI  - The mechanical properties of skin in osteogenesis imperfecta.
AB  - BACKGROUND: Skin mechanics may be affected by several dermatological and systemic
      conditions. The skin can act as a marker of generalized disease. Osteogenesis
      imperfecta (OI) is a heritable disorder characterized by fragile bones caused by
      a generalized disorder of collagen. The dermis has a relative increase of
      argyrophil and elastic fibers and a deficiency of adult collagen. The collagen
      defect is well described, but functional changes in tissue mechanics have not
      been studied in the skin. The functional changes may reflect general changes and
      may give insight into the pathogenesis of clinical problems in these patients.
      OBJECTIVE: To examine skin mechanics (elasticity, distensibility, and hysteresis)
      in patients with OI. METHODS: Ten patients with OI (mean +/- SD age, 45.9 +/-
      11.5 years) and 24 age-matched control subjects (mean +/- SD age, 43.3 +/- 13.8
      years) were studied. The suction cup technique was used (Dermaflex; Cortex
      Technology, Hadsund, Denmark). RESULTS: Significant differences between the
      patients and controls were found in all measurements (P<.002). Skin elasticity
      was decreased in patients vs controls (55.5% [range, 50.9%-60.1%] vs 73.8%
      [range, 70.3%-77.2%]). Similarly, distensibility was decreased (2.10 mm [range,
      1.85-2.35 mm] vs 2.50 mm [range, 2.37-2.63 mm]), as was hysteresis (0.19 mm
      [range, 0.15-0.23 mm] vs 0.28 mm [range, 0.27-0.30 mm]). CONCLUSIONS: The skin of
      patients with OI is more stiff and less elastic than normal skin. It is
      speculated that similar differences may be found in other tissues in patients
      with OI. The results potentially offer a quantitative standardized measure of OI,
      which may further our understanding of the underlying physical problems of these
      patients, provide better case definitions, and assist in predicting the prognosis
      of patients with OI.

PMID- 12071819
TI  - Mediation of alopecia areata by cooperation between CD4+ and CD8+ T lymphocytes:
      transfer to human scalp explants on Prkdc(scid) mice.
AB  - OBJECTIVE: To determine the role of CD4+ and CD8+ T lymphocytes in the
      pathogenesis of alopecia areata. DESIGN: Relapse of alopecia areata was induced
      in autologous human scalp grafts on Prkdc(scid) mice by injection of activated T
      lymphocytes derived from lesional skin. CD4+ and CD8+ T cells were separated by
      magnetic beads before injection. SETTING: University-based dermatology practice.
      PARTICIPANTS: Eleven patients with either alopecia totalis or severe alopecia
      areata. MAIN OUTCOME MEASURES: Hair regrowth, hair loss, and immunohistochemical
      findings of scalp explants. INTERVENTION: Transfer of scalp T cells to autologous
      lesional scalp explants on Prkdc(scid) mice. RESULTS: Injection of unseparated T
      cells and mixed CD4+ plus CD8+ T cells resulted in significant hair loss (P<.01)
      in 5 of 5 experiments. However, injection of purified CD4+ or CD8+ T cells alone
      did not result in reproducible hair loss. CD4+ and CD8+ T cells induced
      follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and
      HLA-A, HLA-B, and HLA-C after injection into scalp grafts. CONCLUSIONS: CD4+ and
      CD8+ T cells have a role in the pathogenesis of alopecia areata. It is
      hypothesized that CD8+ T cells act as the effector cells, with CD4+ T cell help.
      It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with
      alopecia areata. Therapeutic manipulations that interfere with CD8+ activity
      should be examined.

PMID- 12071820
TI  - Sclerodermatous graft-vs-host disease: clinical and pathological study of 17
      patients.
AB  - OBJECTIVE: To collect and review all cases of sclerodermatous chronic graft-vs
      host disease from January 1, 1982, through December 31, 2000. SETTING: University
      hospital in Madrid, Spain. PATIENTS: During the study period, 493 allogenic bone
      marrow transplantations were performed. Sclerotic lesions developed in 17
      patients. RESULTS: Sclerotic lesions appeared after a mean of 529 days.
      Previously, 10 (59%) of 17 patients showed a leopard-skin eruption. Sclerosis was
      generalized in 12 patients and localized in 5. Nine patients presented with
      rippling of the skin and 8 with lichen sclerosus lesions. We found no anti-Scl-70
      or anti-centromere antibodies. Results of histological analysis showed pandermal
      or deep-dermal sclerosis, slight vacuolar degeneration of the basal cell layer,
      and follicular damage with follicular plugs. In 6 (50%) of the 12 patients with
      evaluable biopsy specimens, septal panniculitis was found. Squamous
      syringometaplasia and mucin deposits were also detected. Treatment with high
      doses of prednisone and azathioprine helped in 8 of 9 patients. In 12 patients,
      sclerosis disappeared after 487 days. CONCLUSIONS: Leopard-skin eruption,
      follicular involvement, ripply skin, and lichen sclerosus lesions have been
      described poorly or not at all in sclerodermatous graft-vs-host disease. The
      presence of lichen sclerosus, morphea, septal fibrosis, and fasciitis suggests
      that the sclerosis can start at and affect any level of the skin. Treatment with
      prednisone and azathioprine seems to halt the process. Most patients have a good
      prognosis with treatment. Although most lesions disappear, small areas of
      fibrosis may remain that do not produce any physical or functional impairment.

PMID- 12071822
TI  - Curettage of giant congenital melanocytic nevi in neonates: a decade later.
AB  - BACKGROUND: Currently, there is tremendous uncertainty regarding how giant
      congenital melanocytic nevi (GCMN) should be treated. Our approach to patients
      with GCMN is based on 2 main considerations: (1) obtain an acceptable cosmetic
      result to decrease the psychosocial inconvenience to the patient, and (2) attempt
      to minimize the risk of malignancy. For the past 10 years we have treated GCMN by
      curettage in the neonatal period. We report our experience and results.
      OBSERVATIONS: Sixteen neonates with GCMN were treated by curettage between 1990
      and 2000. Biopsy specimens were obtained and the patients received close clinical
      follow-up. In most patients cosmetic and functional results were good, and, to
      date, no melanoma has been observed in this series. CONCLUSIONS: Curettage offers
      an adequate alternative to surgical excision when performed during the first 2
      weeks of life. Patients and parents are pleased with the cosmetic and functional
      results and thereby suffer less from the psychosocial inconvenience caused by
      these lesions. Careful long-term follow-up of these children is essential to
      monitor final cosmetic outcome and reduce the potential for malignancy.

PMID- 12071821
TI  - Age-related prevalence and antibiotic resistance of pathogenic staphylococci and
      streptococci in children with infected atopic dermatitis at a single-specialty
      center.
AB  - BACKGROUND: Skin staphylococci and streptococci are known to exacerbate atopic
      dermatitis, but the prevalence changes that occur with age are unknown. This
      study examined the age-related prevalence and antibiotic resistance of these
      pathogenic bacteria in children with atopic dermatitis and suspected skin
      infections. OBSERVATIONS: Medical records of 150 children with atopic dermatitis
      referred to a regional center, who had skin swabs taken for suspected infection,
      were studied retrospectively. All patients carried Staphylococcus aureus. The
      prevalence of methicillin sodium-resistant (P =.05) and fusidic acid-resistant (P
      =.001) S aureus tripled from infancy to school age. Lancefield groups A and G
      streptococci were the other pathogens found. The prevalence of group A
      streptococci was highest in children aged 3 to 6 (53%), compared with 11% of
      infants and 21% of patients aged 9 to 16 (P =.002). CONCLUSIONS: Significant
      differences in the age-related prevalence of group A streptococci skin carriage
      and antibiotic resistance of S aureus isolates occurred in this group of children
      with atopic dermatitis and suspected skin infections. Skin swabs to determine
      bacterial type and antibiotic sensitivities provide an important guide to
      antibiotic prescribing in these children.

PMID- 12071823
TI  - Ultrastructural aspects of mucosas in endemic pemphigus foliaceus.
AB  - OBJECTIVE: To investigate whether ultrastructural changes present in clinically
      normal oral mucosa could occur in the mucosas of patients with endemic pemphigus
      foliaceus (EPF) or fogo selvagem (wildfire). PATIENTS: Surgical biopsy specimens
      were taken from the foreskin of 8 patients with EPF and 3 control subjects, the
      uterine cervix and vaginal wall of 9 patients with EPF and 2 controls, and the
      oral mucosa of 5 patients with EPF and 4 controls. The patients received a
      clinical and histopathologic diagnosis of EPF and all had clinically normal oral
      and genital mucosas. RESULTS: In the patients with EPF, widening of the
      intercellular spaces and distended, elongated cytoplasmic projections, the tips
      of which contained desmosomes and were sometimes disassembled, were evident in
      all 4 regions studied. At the periphery of the spinous cells, cytoplasmic
      vesicles apparently containing intact or fragments of desmosomes or half
      desmosomes were seen. CONCLUSIONS: The ultrastructural lesions found in the
      mucosas studied are similar to those previously described in the literature for
      the oral mucosa of patients with EPF. In the cases of EPF, even though the
      desmosomal changes occurred in all epithelial layers, blisters did not occur in
      the mucosas by possible coexpression of desmoglein 1 and desmoglein 3.

PMID- 12071825
TI  - The global dermatological village in Paris.

PMID- 12071824
TI  - Description of a new mutation in hepatoerythropoietic porphyria and prenatal
      exclusion of a homozygous fetus.
AB  - BACKGROUND: Hepatoerythropoietic porphyria (HEP) is usually a severe form of
      cutaneous porphyria, characterized biochemically by an increased urinary
      excretion of polycarboxylated porphyrins. The disease is the result of a profound
      deficiency (<10% of normal activity) of uroporphyrinogen decarboxylase (UROD)
      activity. Hepatoerythropoietic porphyria is inherited as an autosomal recessive
      trait, whereas familial porphyria cutanea tarda is dominant. At least 30
      different mutations of the UROD gene have been identified in patients with HEP
      and familial porphyria cutanea tarda, with 1 predominant missense mutation
      (glycine-to-glutamic acid substitution at codon 281) in Spanish patients with
      HEP. OBSERVATION: A 5-year-old patient with first-degree-related parents
      presented with HEP and mild symptomatology. We found low levels of UROD enzymatic
      activity and a new homozygous mutation of the UROD gene, a phenylanine-to-leucine
      substitution at codon 46 (F46L). Both parents were healthy carriers of the
      mutation. The mother had reduced UROD activity (50% of normal), whereas the
      father had normal UROD activity. Prokaryotic expression of the F46L mutation
      using a pGEX vector has been used to confirm the deleterious effect of the
      mutation. When the mother started a new pregnancy, a prenatal study showed the
      absence of F46L mutation in the fetus and no accumulation of porphyrins in the
      amniotic fluid. CONCLUSIONS: A new mutation in the UROD gene causes a mild HEP
      phenotype. A normal UROD enzymatic activity was observed in the father, despite
      the presence of the heterozygous mutation. To our knowledge, this observation is
      the first description of a prenatal exclusion of HEP.

PMID- 12071827
TI  - When and how should the patient with dermatomyositis or amyopathic
      dermatomyositis be assessed for possible cancer?

PMID- 12071828
TI  - Painful linear nodules.

PMID- 12071829
TI  - Painful plaques on the soles of an HIV-positive man.

PMID- 12071830
TI  - Verrucous plaque in a cardiac transplant recipient.

PMID- 12071831
TI  - Multiple papules on the legs of a woman.

PMID- 12071832
TI  - Pyloric stenosis and pyloric atresia: the same pathogenesis?

PMID- 12071833
TI  - Saline Spa water and UV-B for psoriasis.

PMID- 12071834
TI  - A 10-year-old in situ melanoma?

PMID- 12071835
TI  - Radiotherapy for lentigo maligna.

PMID- 12071836
TI  - Angiolymphoid hyperplasia with eosinophilia associated with anomalous dilatation
      of occipital artery: IL-5 and VEGF expression of lesional mast cells.

PMID- 12071837
TI  - Evaluation of the ability of patients to identify enlarging melanocytic nevi.

PMID- 12071838
TI  - A kinetic model of the co-operative binding of calcium and ADP to scallop
      (Argopecten irradians) heavy meromyosin.
AB  - Analysis of the kinetics of ATP and ADP binding to scallop (Argopecten irradians)
      heavy meromyosin (HMM) showed that the only calcium-dependent process is the rate
      of ADP release. At physiological ionic strength calcium accelerated ADP release
      about 20-fold. Notably in the absence of calcium only one ADP bound HMM, with an
      affinity of 0.5-1 microM. The second nucleotide site remained unoccupied at up to
      50 microM ADP yet could bind ATP rapidly. The calcium dependence of ADP-release
      rates showed that calcium binds co-operatively to scallop HMM with an affinity of
      0.78 microM and a Hill coefficient of 1.9. Detailed interpretation of the data
      suggests that HMM exists in equilibrium between the on and off states and that
      calcium and ADP modulate the equilibrium between the two states. The on state is
      favoured in the presence of calcium and in the absence of both calcium and
      nucleotide. The off state is favoured by ADP (or ADP * P(i)) in the absence of
      calcium. A detailed co-operative model of the interaction of ADP and calcium with
      HMM is presented.

PMID- 12071840
TI  - New insights into heparin binding to vitronectin: studies with monoclonal
      antibodies.
AB  - Vitronectin is a plasma glycoprotein that binds to a variety of ligands. There is
      considerable debate regarding the dependency of these binding interactions upon
      the conformational status of vitronectin, the role of multimerization and how the
      binding of different ligands can change vitronectin's conformational state. We
      have developed a method of capturing vitronectin directly from fresh plasma using
      solid-phase monoclonal antibodies. Various biotin-labelled secondary monoclonal
      antibodies were used to quantify the bound vitronectin and to measure its degree
      of denaturation. Using these tools we demonstrated that one monoclonal antibody
      partially denatured vitronectin without direct multimerization. Treatment of
      vitronectin in plasma with soluble heparin produced a similar degree of
      denaturation. These results led to a proposed adaptation of the
      unfolding/refolding pathways for chemically denatured vitronectin originally
      presented by Zhuang and co-workers in 1996 [Zhuang, Blackburn and Peterson (1996)
      J. Biol. Chem. 271, 14323-14332 and Zhuang, Li, Williams, Wagner, Seiffert and
      Peterson (1996) J. Biol. Chem. 271, 14333-14343]. The adapted version allows for
      the production of a more stable partially unfolded intermediate, resulting from
      the binding of particular ligands. We also demonstrated that the avidity of
      heparin binding to vitronectin is governed by both the conformational state of
      the monomer and multimerization of the molecule.

PMID- 12071839
TI  - Activation of protein kinase CK2 is an early step in the ultraviolet B-mediated
      increase in interstitial collagenase (matrix metalloproteinase-1; MMP-1) and
      stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts.
AB  - Enhanced expression of matrix metalloproteinase (MMP)-1/interstitial collagenase
      and MMP-3/stromelysin-1 in skin fibroblasts and subsequent damage of dermal
      connective tissue in the context of sun-induced premature aging and skin tumour
      progression is causally linked to UVB irradiation. Here, we were interested in
      identifying components of the complex signal-transduction pathway underlying UVB
      mediated up-regulation of these delayed UV-responsive genes and focused on
      components maximally activated early after irradiation. A 2.3-fold increase in
      protein kinase CK2 activity was measured at 20-40 min after low-dose UVB
      irradiation (at 10 mJ/cm2) of dermal fibroblasts. This UVB-mediated increase in
      CK2 activity was abrogated by pharmacological approaches using non-toxic
      concentrations of the CK2 inhibitor 5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole (DRB). Preincubation of fibroblasts with DRB prior to
      UVB irradiation lowered MMP-1 by 49-69% and MMP-3 protein levels by 55-63%
      compared with UVB-irradiated controls. By contrast, the CK2 inhibitor did not
      affect the UVB-triggered transcription of MMPs. Furthermore, UVB irradiation of
      fibroblasts overexpressing a kinase-inactive mutant of CK2 (CK2alpha-K68A-HA)
      resulted in lowering of the protein levels of MMP-1 by 25% and MMP-3 by 22%
      compared with irradiated fibroblasts transfected with the vector control. This
      reduction in MMP protein levels correlated with the transfection efficiency.
      Taken together, we describe a novel aspect of protein kinase CK2, namely its
      inducible activity by UVB irradiation, and provide evidence that CK2 is an early
      mediator of the UVB-dependent up-regulation of MMP-1 and MMP-3 translation,
      whereas their major tissue inhibitor of matrix metalloproteinase-1 is not
      affected by CK2.

PMID- 12071841
TI  - Biochemical identification of a neutral sphingomyelinase 1 (NSM1)-like enzyme as
      the major NSM activity in the DT40 B-cell line: absence of a role in the
      apoptotic response to endoplasmic reticulum stress.
AB  - DT40 cells have approx. 10-fold higher Mg2+-dependent neutral sphingomyelinase
      (NSM) activity in comparison with other B-cell lines and contain very low acidic
      sphingomyelinase activity. Purification of this activity from DT40 cell membranes
      suggested the presence of one major NSM isoform. Although complete purification
      of this isoform could not be achieved, partially purified fractions were examined
      further with regard to the known characteristics of previously partially purified
      NSMs and the two cloned enzymes exhibiting in vitro NSM activity (NSM1 and NSM2).
      For a direct comparative study, highly purified brain preparations, purified NSM1
      protein and Bacillus cereus enzyme were used. Analysis of the enzymic properties
      of the partially purified DT40 NSM, such as cation dependence, substrate
      specificity, redox regulation and stimulation by phosphatidylserine, together
      with the localization of this enzyme to the endoplasmic reticulum (ER), suggested
      that this NSM from DT40 cells corresponds to NSM1. Further studies aimed to
      correlate presence of the high levels of this NSM1-like activity in DT40 cells
      with the ability of these cells to accumulate ceramide and undergo apoptosis.
      When DT40 cells were stimulated to apoptose by a variety of agents, including the
      ER stress, an increase in endogenous ceramide levels was observed. However, these
      responses were not enhanced compared with another B-cell line (Nalm-6),
      characterized by low sphingomyelinase activity. In addition, DT40 cells were not
      more susceptible to ceramide accumulation and apoptosis when exposed to the ER
      stress compared with other apoptotic agents. Inhibition of de novo synthesis of
      ceramide partially inhibited its accumulation, indicating that the ceramide
      production in DT40 cells could be complex and, under some conditions, could
      involve both sphingomyelin hydrolysis and ceramide synthesis.

PMID- 12071842
TI  - Lipid-restricted recognition of mycobacterial lipoglycans by human pulmonary
      surfactant protein A: a surface-plasmon-resonance study.
AB  - The human pulmonary surfactant protein A (hSP-A), a member of the mammalian
      collectin family, is thought to play a key defensive role against airborne
      invading pulmonary pathogens, among which is Mycobacterium tuberculosis, the
      aetiologic agent of tuberculosis. hSP-A has been shown to promote the uptake and
      the phagocytosis of pathogenic bacilli through the recognition and the binding of
      carbohydrate motifs on the invading pathogen surface. Recently we identified
      lipomannan and mannosylated lipoarabinomannan (ManLAM), two major mycobacterial
      cell-wall lipoglycans, as potential ligands for binding of hSP-A. We demonstrated
      that both the terminal mannose residues and the fatty acids are critical for
      binding, whereas the inner arabinosyl and mannosyl domains do not participate. In
      the present study we developed a surface-plasmon-resonance assay to analyse the
      molecular basis for the recognition of ManLAM by hSP-A and to try to define
      further the role of the lipidic aglycone moiety. Binding of ManLAM to immobilized
      hSP-A was consistent with the simplest one-to-one interaction model involving a
      single class of carbohydrate-binding site. This observation strongly suggests
      that the lipid moiety of ManLAM does not directly interact with hSP-A, but is
      rather responsible for the macromolecular organization of the lipoglycan, which
      may be necessary for efficient recognition of the terminal mannosyl epitopes. The
      indirect, structural role of the lipoglycan lipidic component is further
      supported by the complete lack of interaction with hSP-A in the presence of a low
      concentration of mild detergent.

PMID- 12071843
TI  - Biochemical and molecular characterization of two cytidine deaminases in the
      nematode Caenorhabditis elegans.
AB  - Two cytidine deaminases (CDDs) from the free-living nematode Caenorhabditis
      elegans have been cloned and characterized. Both Ce-CDD-1 and Ce-CDD-2 are
      authentic deaminases and both exhibit RNA-binding activity towards AU-rich
      templates. In order to study their temporal and spatial expression patterns in
      the worm, reporter gene constructs were made using approx. 2 kb of upstream
      sequence. Transfection of C. elegans revealed that both genes localized to the
      cells of the intestine, although their temporal expression patterns were
      different. Expression of Ce-cdd-1 peaked in the early larval stages, whereas Ce
      cdd-2 was expressed in all life cycle stages examined. RNA-interference (RNAi)
      assays were performed for both genes, either alone or in combination, but only
      cdd-2 RNAi produced a consistent visible phenotype. A proportion of eggs laid
      from these worms were swollen and distorted in shape.

PMID- 12071844
TI  - The peroxisomal transporter gene ANT1 is regulated by a deviant oleate response
      element (ORE): characterization of the signal for fatty acid induction.
AB  - Saccharomyces cerevisiae ANT1/YPR128c encodes the peroxisomal adenine nucleotide
      transporter that provides ATP for intra-peroxisomal activation of medium-chain
      fatty acids. A lacZ reporter construct comprising the ANT1 promoter was shown to
      be comparatively more highly expressed in a wild-type strain grown on oleic acid,
      a long-chain fatty acid, than in pip2Delta(oaf1)Delta mutant cells that are
      defective in fatty acid induction. The ANT1 promoter was demonstrated to contain
      a deviant oleate response element (ORE) that could bind the Pip2p-Oaf1p
      transcription factor and confer activation on a basal CYC1-lacZ reporter gene.
      Expression of Ant1p as well as other enzymes whose genes are known to be
      regulated by a canonical ORE was found to be increased in cells grown on lauric
      acid, a medium-chain fatty acid. We concluded that the signal for induction does
      not differentiate between long- and medium-chain fatty acids. This signal was
      independent of beta-oxidation or the biogenesis of the peroxisomal compartment
      where this process occurs, since a pox1Delta strain blocked in the first and rate
      limiting step of beta-oxidation as well as various pex mutant cells devoid of
      intact peroxisomes produced sufficient amounts of Pip2p-Oaf1p for binding OREs in
      vitro and for expressing an ORE-driven reporter gene. The signal's durability was
      shown to be related to the concentration of fatty acids in the medium, since a
      pex6Delta strain expressed an ORE-driven reporter gene at high levels for a
      longer period than did isogenic wild-type cells. Generation of the signal was
      also independent of protein synthesis, as demonstrated by cycloheximide
      treatment.

PMID- 12071845
TI  - The chitinase 3-like protein human cartilage glycoprotein 39 (HC-gp39) stimulates
      proliferation of human connective-tissue cells and activates both extracellular
      signal-regulated kinase- and protein kinase B-mediated signalling pathways.
AB  - Human cartilage glycoprotein 39 (HC-gp39) is a glycoprotein secreted by articular
      chondrocytes, synoviocytes and macrophages. Increased levels of HC-gp39 have been
      demonstrated in synovial fluids of patients with rheumatoid or osteoarthritis.
      The increased secretion of HC-gp39 under physiological and pathological
      conditions with elevated connective-tissue turnover suggests its involvement in
      the homoeostasis of these tissues. We report here that HC-gp39 promotes the
      growth of human synovial cells as well as skin and fetal lung fibroblasts. A dose
      dependent growth stimulation was observed when each of the fibroblastic cell
      lines was exposed to HC-gp39 in a concentration range from 0.1 to 2 nM, which is
      similar to the effective dose of the well-characterized mitogen, insulin-like
      growth factor-1. At suboptimal concentrations, the two growth factors work in a
      synergistic fashion. The use of selective inhibitors of the mitogen-activated
      protein kinase and the protein kinase B (AKT) signalling pathways indicates that
      both are involved in mediating the mitogenic response to HC-gp39. Phosphorylation
      of both extracellular signal-regulated kinases 1/2 and AKT occurred in a dose-
      and time-dependent fashion upon addition of HC-gp39. Activation of these
      signalling pathways could also be demonstrated in human chondrocytes. Thus HC
      gp39 initiates a signalling cascade in connective-tissue cells which leads to
      increased cell proliferation, suggesting that this protein could play a major
      role in the pathological conditions leading to tissue fibrosis.

PMID- 12071846
TI  - Regulation of phagosomal iron release from murine macrophages by nitric oxide.
AB  - The role of NO in macrophage iron turnover was studied in macrophages from
      inducible nitric oxide synthase (iNOS)-deficient mice. Interferon
      gamma/lipopolysaccharide (IFNgamma/LPS)-activated bone marrow-derived macrophages
      from iNOS-deficient mice, following phagocytosis of 59Fe-labelled transferrin
      anti-transferrin immune complexes, showed reduced iron release compared with
      cells from wild-type iNOS littermates. Uptake of the complexes by macrophages was
      similar in iNOS-deficient and wild-type mice. Ferritin was up-regulated by
      IFNgamma/LPS treatment, but NO exercised a modest opposing down-regulatory
      effect. No effect of iNOS deficiency was seen when iron was taken up from iron
      citrate, which enters via a non-phagocytic route. These results suggest that NO
      plays a key role in regulating iron turnover in macrophages acquiring iron by
      phagocytosis of erythrocytes or cell debris, and thus the supply to peripheral
      tissues, such as to the bone marrow for erythropoiesis.

PMID- 12071847
TI  - UVB-mediated activation of p38 mitogen-activated protein kinase enhances
      resistance of normal human keratinocytes to apoptosis by stabilizing cytoplasmic
      p53.
AB  - Human keratinocytes respond to UV rays by developing a fast adaptive response
      that contributes to maintaining their functions and survival. We investigated the
      role of the mitogen-activated protein kinase pathways in transducing the UV
      signals in normal human keratinocytes. We found that UVA, UVB or UVC induced a
      marked and persistent activation of p38, whereas c-Jun N-terminal kinase or
      extracellular signal-regulated kinase were less or not activated respectively.
      Inhibition of p38 activity by expression of a dominant-negative mutant of p38 or
      with SB203580 impaired cell viability and led to an increase in UVB-induced
      apoptosis. This sensitization to apoptosis was independent of caspase activities.
      Inhibition of p38 did not sensitize transformed HaCaT keratinocytes to UVB
      induced apoptosis. In normal keratinocytes, expression of a dominant-negative
      mutant of p53 increased UVB-induced cell death, pointing to a role for p53. In
      these cells, UVB triggered a p38-dependent phosphorylation of p53 on Ser-15. This
      phosphorylation was associated with an SB203580-sensitive accumulation of p53,
      even in the presence of a serine phosphatase inhibitor. Accumulated p53 was
      localized mainly in the cytoplasm, independently of CRM1 nuclear export. In HaCaT
      cells, p53 was localized exclusively in the nucleus and its distribution and
      level were not affected by UVB or p38 inhibition. However, UVB induced an
      SB203580-insensitive phosphorylation on Ser-15 of mutated p53. Overall, our
      results suggest that, in normal human keratinocytes, protection against UVB
      depends on p38-mediated phosphorylation and stabilization of p53 and is tightly
      associated with the cytoplasmic sequestration of wild-type p53. We conclude that
      the p38/p53 pathway plays a key role in the adaptive response of normal human
      keratinocytes against UV stress.

PMID- 12071848
TI  - Leukotriene D4 induces association of active RhoA with phospholipase C-gamma1 in
      intestinal epithelial cells.
AB  - It has been previously suggested that leukotriene-induced Ca2+ signalling is
      mediated through a Rho-dependent process, but neither direct activation of Rho
      nor a mechanism underlying such signalling has been reported. Accordingly, we
      used the Rhotekin binding assay to assess RhoA activation in intestinal
      epithelial cells and observed that RhoA was activated by leukotriene D4 (LTD4).
      We also found that, within 15 s, activation of RhoA by LTD4 led to an increased
      association of RhoA with G-protein betagamma (Gbetagamma) and phospholipase C
      gamma1 (PLC-gamma1) in the plasma membrane, as evidenced by the results of co
      immunoprecipitation, glutathione S-transferase (GST) pulldown assays, and
      confocal microscopy. Amounts of RhoA increased in both Gbeta and PLC-gamma1
      immunoprecipitates within 15 s of LTD4 treatment. An interaction between RhoA,
      Gbetagamma and PLC-gamma1 is supported by our finding that a GST fusion protein
      of constitutively active RhoA (GST-RhoAV14) precipitated Gbetagamma and PLC
      gamma1 from cell lysates in an agonist-dependent manner. Such an association is
      also substantiated by our confocal immunofluorescence results, which revealed
      that LTD4 induction increased co-localization of constitutively active RhoA and
      PLC-gamma1 to the plasma membrane of cells transfected with enhanced green
      fluorescent protein L63RhoA. Furthermore, microinjection of neutralizing RhoA
      antibodies, but not control antibodies, significantly reduced LTD4-induced Ca2+
      mobilization. Our results are the first to demonstrate a LTD4-induced activation
      of RhoA and more importantly its association with PLC-gamma1, which are essential
      for the PLC-gamma1-mediated calcium mobilization.

PMID- 12071849
TI  - Fluorescently labelled bovine acyl-CoA-binding protein acting as an acyl-CoA
      sensor: interaction with CoA and acyl-CoA esters and its use in measuring free
      acyl-CoA esters and non-esterified fatty acids.
AB  - Long-chain acyl-CoA esters are key metabolites in lipid synthesis and beta
      oxidation but, at the same time, are important regulators of intermediate
      metabolism, insulin secretion, vesicular trafficking and gene expression. Key
      tools in studying the regulatory functions of acyl-CoA esters are reliable
      methods for the determination of free acyl-CoA concentrations. No such method is
      presently available. In the present study, we describe the synthesis of two acyl
      CoA sensors for measuring free acyl-CoA concentrations using acyl-CoA-binding
      protein as a scaffold. Met24 and Ala53 of bovine acyl-CoA-binding protein were
      replaced by cysteine residues, which were covalently modified with 6-bromoacetyl
      2-dimethylaminonaphthalene to make the two fluorescent acyl-CoA indicators
      (FACIs) FACI-24 and FACI-53. FACI-24 and FACI-53 showed fluorescence emission
      maximum at 510 and 525 nm respectively, in the absence of ligand (excitation 387
      nm). Titration of FACI-24 and FACI-53 with hexadecanoyl-CoA and dodecanoyl-CoA
      increased the fluorescence yield 5.5-and 4.7-fold at 460 and 495 nm respectively.
      FACI-24 exhibited a high, and similar increase in, fluorescence yield at 460 nm
      upon binding of C14-C20 saturated and unsaturated acyl-CoA esters. Both
      indicators bind long-chain (>C14) acyl-CoA esters with high specificity and
      affinity (K(d)=0.6-1.7 nM). FACI-53 showed a high fluorescence yield for C8-C12
      acyl chains. It is shown that FACI-24 acts as a sensitive acyl-CoA sensor for
      measuring the concentration of free acyl-CoA, acyl-CoA synthetase activity and
      the concentrations of free fatty acids after conversion of the fatty acid into
      their respective acyl-CoA esters.

PMID- 12071850
TI  - Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human.
AB  - Synaptotagmin VII (Syt VII) has been proposed to regulate several different types
      of Ca2+-dependent exocytosis, but its subcellular localization (lysosome or
      plasma membrane) and the number of alternative splicing isoforms of Syt VII
      (single or multiple forms) are matters of controversy. In the present study, we
      show by reverse transcriptase-PCR analysis that mouse Syt VII has one major
      isoform (Syt VIIalpha), the original Syt VII, and two minor isoforms (Syt VIIbeta
      and Syt VIIgamma), which contain unique insertions (of 44 and 116 amino acids
      respectively) in the spacer domain between the transmembrane and C2 domains of
      Syt VIIalpha. Similar results were obtained with respect to rat and human Syt VII
      mRNA expression. An antibody against the N-terminal domain of mouse Syt VII [anti
      (Syt VII-N)], which specifically recognized recombinant Syt VII but not other Syt
      isoforms expressed in COS-7 cells, recognized two major, closely co-migrating
      bands (p58 and p60) and minor bands of approx. 65 kDa in mouse brain.
      Immunoaffinity purification of proteins that bind the anti-(Syt VII-N) antibody,
      and peptide sequence analysis revealed that: (i) the major p58 and p60 bands are
      identified as adenylate cyclase-associated protein 2; (ii) actin-binding protein
      is localized at the plasma membrane; and (iii) Syt VIIalpha (65 kDa) is the major
      Syt VII isoform, but with a much lower expression level than previously thought.
      It was also shown that FLAG-Syt VII-green-fluorescence-protein fusion protein
      stably expressed in PC12 cells is localized in the perinuclear region (co
      localization with TGN38 protein, even after brefeldin A treatment) and in the
      tips of neurites (co-localization with Syt I), and not in the plasma membrane.

PMID- 12071851
TI  - Decreased activity and enhanced nuclear export of CCAAT-enhancer-binding protein
      beta during inhibition of adipogenesis by ceramide.
AB  - To identify novel molecular mechanisms by which ceramide regulates cell
      differentiation, we examined its effect on adipogenesis of 3T3-L1 preadipocytes.
      Hormonal stimulation of 3T3-L1 preadipocytes induced formation of triacylglycerol
      laden adipocytes over 7 days; in part, via the co-ordinated action of CCAAT
      enhancer-binding proteins alpha, beta and delta (C/EBP-alpha, -beta and -delta)
      and peroxisome-proliferator-activated receptor gamma (PPARgamma). The addition of
      exogenous N-acetylsphingosine (C2-ceramide) or increasing endogenous ceramide
      levels inhibited the expression of C/EBPalpha and PPARgamma, and blocked
      adipocyte development. C2-ceramide did not decrease the cellular expression of
      C/EBPbeta, which is required for expression of C/EBPalpha and PPARgamma, but
      significantly blocked its transcriptional activity from a promoter construct
      after 24 h. The ceramide-induced decrease in the transcriptional activity of
      C/EBPbeta correlated with a strong decrease in its phosphorylation, DNA-binding
      ability and nuclear localization at 24 h. However, ceramide did not change the
      nuclear level of C/EBPbeta after a period of 4 or 16 h, suggesting that it was
      not affecting nuclear import. CRM1 (more recently named 'exportin-1') is a
      nuclear membrane protein that regulates protein export from the nucleus by
      binding to a specific nuclear export sequence. Leptomycin B is an inhibitor of
      CRM1/exportin-1, and reversed the ceramide-induced decrease in nuclear C/EBPbeta
      at 24 h. Taken together, these data support the hypothesis that ceramide may
      inhibit adipogenesis, at least in part, by enhancing dephosphorylation and
      premature nuclear export of C/EBPbeta at a time when its maximal transcriptional
      activity is required to drive adipogenesis.

PMID- 12071852
TI  - An intron-containing glycoside hydrolase family 9 cellulase gene encodes the
      dominant 90 kDa component of the cellulosome of the anaerobic fungus Piromyces
      sp. strain E2.
AB  - The cellulosome produced by Piromyces sp. strain E2 during growth on filter paper
      was purified by using an optimized cellulose-affinity method consisting of steps
      of EDTA washing of the cellulose-bound protein followed by elution with water.
      Three dominant proteins were identified in the cellulosome preparation, with
      molecular masses of 55, 80 and 90 kDa. Treatment of cellulose-bound cellulosome
      with a number of denaturing agents was also tested. Incubation with 0.5% (w/v)
      SDS or 8 M urea released most cellulosomal proteins, while leaving the greater
      fraction of the 80, 90 and 170 kDa components. To investigate the major 90 kDa
      cellulosome protein further, the corresponding gene, cel9A, was isolated, using
      immunoscreening and N-terminal sequencing. Inspection of the cel9A genomic
      organization revealed the presence of four introns, allowing the construction of
      a consensus for introns in anaerobic fungi. The 2800 bp cDNA clone contained an
      open reading frame of 2334 bp encoding a 757-residue extracellular protein. Cel9A
      includes a 445-residue glycoside hydrolase family 9 catalytic domain, and so is
      the first fungal representative of this large family. Both modelling of the
      catalytic domain as well as the activity measured with low level expression in
      Escherichia coli indicated that Cel9A is an endoglucanase. The catalytic domain
      is succeeded by a putative beta-sheet module of 160 amino acids with unknown
      function, followed by a threonine-rich linker and three fungal docking domains.
      Homology modelling of the Cel9A dockerins suggested that the cysteine residues
      present are all involved in disulphide bridges. The results presented here are
      used to discuss evolution of glycoside hydrolase family 9 enzymes.

PMID- 12071853
TI  - Isolation and characterization of the monkey UGT2B30 gene that encodes a uridine
      diphosphate-glucuronosyltransferase enzyme active on mineralocorticoid,
      glucocorticoid, androgen and oestrogen hormones.
AB  - The present study reports the genomic organization and the characterization of a
      novel cynomolgus monkey UDP-glucuronosyltransferase (UGT) enzyme, UGT2B30. UGT
      enzymes are microsomal proteins that catalyse the transfer of the glucuronosyl
      group from UDP-glucuronic acid (UDPGA) to a wide variety of lipophilic compounds,
      namely hormonal steroids. The 15 kb UGT2B30 gene amplified by PCR showed a
      genomic organization similar to those encoding UGT2B human enzymes. The cDNA
      encoding UGT2B30 was isolated from a cynomolgus monkey prostate cDNA library, and
      the deduced amino acid sequence showed an identity of 94% with UGT2B19, a monkey
      isoform previously characterized. Stable expression of UGT2B30 protein in human
      kidney 293 (HK293) cells was assessed by Western-blot analysis and its
      conjugating activity was screened using 39 potential substrates. The UGT2B30
      enzyme is active on many compounds of different classes, including testosterone,
      dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol, androsterone,
      oestradiol, tetrahydroaldosterone and tetrahydrocortisone, with glucuronidation
      efficiencies (V(max)/K(m) ratios) ranging from 0.6 to 8.8 microl x min(-1) x mg
      of protein(-1). Reverse-transcriptase-PCR analysis revealed that the UGT2B30
      transcript is expressed in several tissues, including prostate, testis, mammary
      gland, kidney, adrenals and intestine. The relative activity of UGT2B30 in
      comparison with other simian UGT2B isoforms, as well as its large variety of
      substrates, strongly suggest that this enzyme is essential to inactivation of
      several steroids.

PMID- 12071854
TI  - Transport of phosphatidylserine via MDR1 (multidrug resistance 1)P-glycoprotein
      in a human gastric carcinoma cell line.
AB  - The ATP-binding cassette transporter multidrug resistance 1 P-glycoprotein (MDR1
      Pgp) has been implicated with the transport of lipids from the inner to the outer
      leaflet of the plasma membrane. While this has been unambigously shown for the
      fluorescent lipid analogues [N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoyl
      (C6-NBD)-phosphatidylcholine, -phosphatidylethanolamine, -sphingomyelin and 
      glucosylceramide, by using a novel approach we have now found significantly
      increased outward transport also for C6-NBD-phosphatidylserine (C6-NBD-PS) in
      EPG85-257 human gastric carcinoma cells overexpressing MDR1 (coding for MDR1
      Pgp). The increased transport of C6-NBD-PS is mediated by MDR1 Pgp, shown by
      transport reduction nearly to the level of controls in the presence of MDR1 Pgp
      inhibitors [PSC 833, cyclosporin A and dexniguldipine hydrochloride (Dex)].
      Addition of MK 571, a specific inhibitor of the MDR protein MRP1, does not
      decrease transport in either of the two cell lines. The plasma-membrane
      association of FITC-annexin V, a fluorescent protein conjugate binding PS, is
      significantly increased in MDR1-overexpressing cells as compared with controls,
      and can be reduced by an MDR1 Pgp inhibitor. This suggests that MDR1 Pgp
      transports endogenous PS, the lipid exhibiting the most pronounced transverse
      asymmetry in the plasma membrane.

PMID- 12071856
TI  - In vitro selection of fibronectin gain-of-function mutations.
AB  - Directed protein evolution, which employs a combination of random mutagenesis,
      phage display, and in vitro selection, was used to identify second-site
      suppressors of the fibronectin (Fn) cell binding domain mutation Asp1495Ala
      (RGA). The mutations in the Fn 9th (3fn9) and 10th (3fn10) type III repeats
      obtained after selection on purified integrins alphaIIbbeta3(D119Y) and
      alpha5beta1 are reported. The 3fn9-10(D1495A) phage with substitution mutations
      at Asp1418, which is located within the linker region between 3fn9 and 3fn10,
      enhanced binding to the integrins alphaIIbbeta3 and alpha5beta1, but not
      alphavbeta3. The substitution mutations identified at residue Asp1418 were
      introduced into the native recombinant 3fn9-10 sequence and found to augment
      binding to alphaIIbbeta3, demonstrating that the observed gain-of-function
      phenotype was independent of the multivalent character of the phage. These
      results support the following conclusions. First, regions of Fn in addition to
      the RGD loop are in close proximity to alphaIIbbeta3 and alpha5beta1 and are
      capable of participating in the binding to these integrins. Secondly, the
      conformational relationship between the 3fn9 and 3fn10 modules may be an
      important factor in the binding of Fn to these two integrins. Thirdly, other
      altered properties of Fn-integrin interactions, such as integrin specificity, may
      also be selected. This is the first description of Fn mutations that augment
      binding to integrins. The ability to select for particular phenotypes in vitro
      and the subsequent characterization of these mutations should further our
      understanding of the molecular details involved in the association of integrins
      and their ligands. Additionally, these higher-affinity 3fn9-10 ligands provide a
      starting point for further in vitro evolution and engineering of integrin
      specific modules.

PMID- 12071855
TI  - Ferritin binds to light chain of human H-kininogen and inhibits kallikrein
      mediated bradykinin release.
AB  - Ferritin is an iron-storage protein that exists in both intracellular and
      extracellular compartments. We have previously identified H-kininogen (high
      molecular-weight kininogen) as a ferritin-binding protein [Torti and Torti (1998)
      J. Biol. Chem. 273, 13630-13635]. H-Kininogen is a precursor of the potent pro
      inflammatory peptide bradykinin, which is released from H-kininogen following
      cleavage of H-kininogen by the serine protease kallikrein. In this report, we
      demonstrate that binding of ferritin to H-kininogen occurs via the modified light
      chain of H-kininogen, and that ferritin binds preferentially to activated H
      kininogen. We further demonstrate that binding of ferritin to H-kininogen retards
      the proteolytic cleavage of H-kininogen by kallikrein and its subsequent release
      of bradykinin from H-kininogen. Ferritin does not interfere with the ability of
      kallikrein to digest a synthetic substrate, suggesting that ferritin specifically
      impedes the ability of kallikrein to digest H-kininogen, perhaps by steric
      hindrance. Based on these results, we propose a model of sequential H-kininogen
      cleavage and ferritin binding. These results are consistent with the hypothesis
      that the binding of ferritin to H-kininogen may serve to modulate bradykinin
      release.

PMID- 12071857
TI  - Role of alphaArg145 and betaArg263 in the active site of penicillin acylase of
      Escherichia coli.
AB  - The active site of penicillin acylase of Escherichia coli contains two conserved
      arginine residues. The function of these arginines, alphaArg145 and betaArg263,
      was studied by site-directed mutagenesis and kinetic analysis of the mutant
      enzymes. The mutants alphaArg145-->Leu (alphaArg145Leu), alphaArg145Cys and
      alphaArg145Lys were normally processed and exported to the periplasm, whereas
      expression of the mutants betaArg263Leu, betaArg263Asn and betaArg263Lys yielded
      large amounts of precursor protein in the periplasm, indicating that betaArg263
      is crucial for efficient processing of the enzyme. Either modification of both
      arginine residues by 2,3-butanedione or replacement by site-directed mutagenesis
      yielded enzymes with a decreased specificity (kcat/K(m)) for 2-nitro-5
      [(phenylacetyl)amino]benzoic acid, indicating that both residues are important in
      catalysis. Compared with the wild type, the alphaArg145 mutants exhibited a 3-6
      fold-increased preference for 6-aminopenicillanic acid as the deacylating
      nucleophile compared with water. Analysis of the steady-state parameters of these
      mutants for the hydrolysis of penicillin G and phenylacetamide indicated that
      destabilization of the Michaelis-Menten complex accounts for the improved
      activity with beta-lactam substrates. Analysis of pH-activity profiles of wild
      type enzyme and the betaArg263Lys mutant showed that betaArg263 has to be
      positively charged for catalysis, but is not involved in substrate binding. The
      results provide an insight into the catalytic mechanism of penicillin acylase, in
      which alphaArg145 is involved in binding of beta-lactam substrates and betaArg263
      is important both for stabilizing the transition state in the reaction and for
      correct processing of the precursor protein.

PMID- 12071858
TI  - The hyaluronan lyase of Streptococcus pyogenes bacteriophage H4489A.
AB  - Many pathogenic streptococci produce extracellular hyaluronan lyases which are
      thought to aid the spread of the organism in host tissues. In addition, several
      phages of group A streptococci are known to synthesize a bound form of
      hyaluronidase. It has been suggested that the function of this hyaluronidase is
      to facilitate penetration of the hyaluronan capsule by phage and thus to gain
      access for the phage to the cell surface of the host streptococcus [Hynes,
      Hancock and Ferretti (1995) Infect. Immun. 63, 3015-3020]. In the present work,
      the hyaluronidase of Streptococcus pyogenes bacteriophage H4489A, expressed in E.
      coli, has been purified and characterized. The enzyme was shown to be a lyase
      with a distributive action pathway. Unlike most bacterial hyaluronidases that
      have been characterized, the phage enzyme was found to specifically cleave
      hyaluronan, which adds credence to the view that its function is to digest the
      hyaluronan capsule of the host organism. This bacteriophage lyase may provide a
      practical alternative to the lyase from Streptomyces hyalurolyticus as a reagent
      for the specific cleavage of hyaluronan.

PMID- 12071859
TI  - A mammalian Rho-specific guanine-nucleotide exchange factor (p164-RhoGEF) without
      a pleckstrin homology domain.
AB  - Rho GTPases, which are activated by specific guanine-nucleotide exchange factors
      (GEFs), play pivotal roles in several cellular functions. We identified a
      recently cloned human cDNA, namely KIAA0337, encoding a protein containing 1510
      amino acids (p164). It contains a RhoGEF-specific Dbl homology (DH) domain but
      lacks their typical pleckstrin homology domain. The expression of the mRNA
      encoding p164 was found to be at least 4-fold higher in the heart than in other
      tissues. Recombinant p164 interacted with and induced GDP/GTP exchange at RhoA
      but not at Rac1 or Cdc42. p164-DeltaC and p164-DeltaN are p164 mutants that are
      truncated at the C- and N-termini respectively but contain the DH domain. In
      contrast with the full-length p164, expression of p164-DeltaC and p164-DeltaN
      strongly induced actin stress fibre formation and activated serum response factor
      mediated and Rho-dependent gene transcription. Interestingly, p164-DeltaN2, a
      mutant containing the C-terminus but having a defective DH domain, bound to p164
      DeltaC and suppressed the p164-DeltaC-induced gene transcription. Overexpression
      of the full-length p164 inhibited M(3) muscarinic receptor-induced gene
      transcription, whereas co-expression with Gbeta(1)gamma(2) dimers induced
      transcriptional activity. It is concluded that p164-RhoGEF is a Rho-specific GEF
      with novel structural and regulatory properties and predominant expression in the
      heart. Apparently, its N- and C-termini interact with each other, thereby
      inhibiting its GEF activity.

PMID- 12071860
TI  - Endoplasmic reticulum resident proteins of normal human dermal fibroblasts are
      the major targets for oxidative stress induced by hydrogen peroxide.
AB  - The membrane-permeable fluorescein-labelled tyramine conjugate (acetylTyrFluo)
      was used to identify the proteins of normal human dermal fibroblasts most
      susceptible to oxidation by hydrogen peroxide [Van der Vlies, Wirtz and Pap
      (2001) Biochemistry 40, 7783-7788]. By exposing the cells to H(2)O(2) (0.1 mM for
      10 min), TyrFluo was covalently linked to target proteins. TyrFluo-labelled and
      [(35)S]Met-labelled cell lysates were mixed and subjected to two-dimensional
      PAGE. After Western blotting the (35)S-labelled proteins were visualized by
      autoradiography and the TyrFluo-labelled proteins by using anti-fluorescein
      antibody. The TyrFluo-labelled proteins were matched with the (35)S-labelled
      proteins and identified by comparison with our mastermap of proteins. Protein
      disulphide isomerase (PDI), IgG-binding protein (BiP), calnexin, endoplasmin and
      glucose-regulated protein 58 (endoplasmic reticulum protein 57/GRP58) were
      identified as targets of oxidation. All these proteins reside in the endoplasmic
      reticulum and are part of the protein folding machinery. In agreement, confocal
      laser scanning microscopy showed co-localization of TyrFluo-labelled proteins and
      the KDEL receptor ERD-2, a marker for the endoplasmic reticulum.

PMID- 12071861
TI  - Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that
      associate with the Golgi apparatus define a distinct subclass of aldo-keto
      reductase 7 family proteins.
AB  - The aldo-keto reductase (AKR) 7 family is composed of the dimeric aflatoxin B(1)
      aldehyde reductase (AFAR) isoenzymes. In the rat, two AFAR subunits exist,
      designated rAFAR1 and rAFAR2. Herein, we report the molecular cloning of rAFAR2,
      showing that it shares 76% sequence identity with rAFAR1. By contrast with
      rAFAR1, which comprises 327 amino acids, rAFAR2 contains 367 amino acids. The 40
      extra residues in rAFAR2 are located at the N-terminus of the polypeptide as an
      Arg-rich domain that may form an amphipathic alpha-helical structure. Protein
      purification and Western blotting have shown that the two AFAR subunits are found
      in rat liver extracts as both homodimers and as a heterodimer. Reductase activity
      in rat liver towards 2-carboxybenzaldehyde (CBA) was resolved by anion-exchange
      chromatography into three peaks containing rAFAR1-1, rAFAR1-2 and rAFAR2-2
      dimers. These isoenzymes are functionally distinct; with NADPH as cofactor,
      rAFAR1-1 has a low K(m) and high activity with CBA, whereas rAFAR2-2 exhibits a
      low K(m) and high activity towards succinic semialdehyde. These data suggest that
      rAFAR1-1 is a detoxication enzyme, while rAFAR2-2 serves to synthesize the
      endogenous neuromodulator gamma-hydroxybutyrate (GHB). Subcellular fractionation
      of liver extracts showed that rAFAR1-1 was recovered in the cytosol whereas
      rAFAR2-2 was associated with the Golgi apparatus. The distinct subcellular
      localization of the rAFAR1 and rAFAR2 subunits was confirmed by
      immunocytochemistry in H4IIE cells. Association of rAFAR2-2 with the Golgi
      apparatus presumably facilitates secretion of GHB, and the novel N-terminal
      domain may either determine the targeting of the enzyme to the Golgi or regulate
      the secretory process. A murine AKR protein of 367 residues has been identified
      in expressed sequence tag databases that shares 91% sequence identity with rAFAR2
      and contains the Arg-rich extended N-terminus of 40 amino acids. Further
      bioinformatic evidence is presented that full-length human AKR7A2 is composed of
      359 amino acids and also possesses an additional N-terminal domain. On the basis
      of these observations, we conclude that AKR7 proteins can be divided into two
      subfamilies, one of which is a Golgi-associated GHB synthase with a unique,
      previously unrecognized, N-terminal domain that is absent from other AKR
      proteins.

PMID- 12071863
TI  - Anterior lens capsule disruption and suspected malignant glaucoma in a dog.
AB  - A Boston Terrier puppy presented with a full-thickness peripheral corneal defect,
      iris prolapse and anterior lens capsule tear in the left eye (OS).
      Phacofragmentation and primary repair of the corneal laceration was performed. At
      surgery, subluxation of the lens was also apparent. One day postoperative, there
      was severe corneal edema, diffuse hyphema, an intraocular pressure (IOP) of 65
      mmHg and a small amount of vitreous that protruded from the corneal incision OS.
      Malignant glaucoma or pupillary block glaucoma were suspected. Intravenous
      mannitol was administered preoperatively and had no effect. An anterior
      vitrectomy was performed on the vitreous within the anterior chamber and pupil.
      One day postoperative the IOP was 16 mmHg in the right eye (OD) and 20 mmHg OS.
      Postoperative iridocyclitis was managed medically, and additional elevations in
      IOP were not recorded. Resolution of the elevated IOP following anterior
      vitrectomy was supportive of pupillary block or malignant glaucoma. Vision
      returned 3 weeks after the initial surgery. Two years after the initial injury,
      the eye is visual and comfortable with infrequent topical anti-inflammatory
      therapy.

PMID- 12071862
TI  - Effects of L- and D-REKR amino acid-containing peptides on HIV and SIV envelope
      glycoprotein precursor maturation and HIV and SIV replication.
AB  - The aim of the present study was to evaluate the capacity of synthetic l- and d
      peptides encompassing the HIV-1(BRU) gp160 REKR cleavage site to interfere with
      HIV and simian immuno-deficiency virus (SIV) replication and maturation of the
      envelope glycoprotein (Env) precursors. To facilitate their penetration into
      cells, a decanoyl (dec) group was added at the N-terminus. The sequences
      synthesized included dec5d or dec5l (decREKRV), dec9d or dec9l (decRVVQREKRV) and
      dec14d or dec14l (TKAKRRVVQREKRV). The peptide dec14d was also prepared with a
      chloromethane (cmk) group as C-terminus. Because l-peptides exhibit significant
      cytotoxicity starting at 35 microM, further characterization was conducted mostly
      with d-peptides, which exhibited no cytotoxicity at concentrations higher than 70
      microM. The data show that only dec14d and dec14dcmk could inhibit HIV-1(BRU),
      HIV-2(ROD) and SIV(mac251) replication and their syncytium-inducing capacities.
      Whereas peptides dec5d and dec9d were inactive, dec14dcmk was at least twice as
      active as peptide dec14d. At the molecular level, our data show a direct
      correlation between anti-viral activity and the ability of the peptides to
      interfere with maturation of the Env precursors. Furthermore, we show that when
      tested in vitro the dec14d peptide inhibited PC7 with an inhibition constant
      K(i)=4.6 microM, whereas the peptide dec14l preferentially inhibited furin with a
      K(i)=28 microM. The fact that PC7 and furin are the major prohormone convertases
      reported to be expressed in T4 lymphocytes, the principal cell targets of HIV,
      suggests that they are involved in the maturation of HIV and SIV Env precursors.

PMID- 12071864
TI  - Technical issues in electrodiagnostic recording.
AB  - Electroretinogram (ERG) and visual-evoked potentials (VEPs) are used in
      veterinary ophthalmology to assess the functional integrity of the retina and the
      central visual pathway. The interpretation of altered electrophysiologic
      potentials in diseases can be of great diagnostic value, although it is important
      to be aware of technical factors and the limitations of these techniques which
      may result in over-interpretation and misinterpretation of the recordings, such
      that they are similar to those found in disease-related electrophysiologic
      changes. The recorded potentials represent the differences in voltage between the
      active and reference electrodes. The ground electrode serves as zero. A
      differential or instrumentation amplifier selectively amplifies signals of
      interest while rejecting noise. Differences between inputs are amplified, whereas
      common signals are rejected in a process called common mode rejection (CMR). In
      order for CMR to be most effective in reducing noise, the electrode impedances
      should be balanced. Filters are part of the differential amplifier as they remove
      unwanted noise of a certain frequency. The frequency bandwidth, or passband, is
      the range of frequencies between low- and high-frequency filter settings that are
      not filtered out. Major sources of noise that cause interpretation artifacts are
      power lines, amplifier noise, physiologic activity, electrochemical electrode
      noise and circular grounds. Noise reduction is achieved with high amplifier input
      impedance, balanced electrode impedances, CMR, filters and signal averaging.
      Maintaining electrodes in good condition, achieving proper contact between
      electrode and animal, and keeping electrode leads short aid in achieving noise
      reduction.

PMID- 12071865
TI  - Causes of uveitis in dogs: 102 cases (1989-2000).
AB  - Uveitis is one of the most common ocular diseases and one of the most common
      causes of blindness in dogs. The purpose of this retrospective study was to
      correlate the signalment, history, clinical signs and ophthalmic findings of dogs
      with uveitis with the underlying etiology. We conducted a retrospective study of
      102 dogs presented to the NCSU-VTH from 1989 to 2000 with clinical signs of
      uveitis. Medical records of dogs presented for uveitis were reviewed. Dogs were
      included in the study only if a complete diagnostic work-up database was
      collected, if sufficient follow-up was documented, and if the uveitis was not
      secondary to trauma or a hypermature cataract. The mean age +/- SD of all dogs in
      this study was 6.2 +/- 3.6 years. There were 33 intact and 16 castrated males,
      and 14 intact and 27 neutered females. Fourteen breeds were represented, with the
      Golden Retriever (n = 14) most common. Fifty-nine dogs (58%) were diagnosed with
      idiopathic/immune-mediated uveitis, neoplasia was diagnosed in 25 dogs (24.5%)
      and 18 dogs (17.6%) were diagnosed with infectious causes of uveitis. Aqueous
      flare was the most common clinical sign, occurring in 88 dogs (86%). The most
      common infectious organisms associated with uveitis in the dogs of this study
      were Ehrlichia canis (n = 7). Lymphosarcoma (n = 17) was the most common
      neoplasm. In approximately 60% of dogs presenting for uveitis an underlying cause
      was not found, and a diagnosis of immune-mediated or idiopathic uveitis was made.
      However, approximately 25% of dogs had ocular and/or systemic neoplasia (with 17%
      of cases having lymphosarcoma) and 18% with an underlying infectious cause for
      uveitis. Because of the high percentage of systemic disease associated with
      uveitis in dogs, extensive diagnostic testing is recommended before instituting
      symptomatic anti-inflammatory therapy.

PMID- 12071866
TI  - Aqueous misdirection and ciliary block (malignant) glaucoma after cataract
      removal in a llama.
AB  - Ciliary block (malignant) glaucoma is caused by the posterior flow of aqueous
      humor into or behind the vitreous. It is a rare complication of anterior segment
      surgery in humans. This is a report of ciliary block glaucoma occurring as a
      postoperative complication of cataract surgery in a llama. Medical management was
      ineffective in lowering intraocular pressure (IOP). Posterior capsulotomy and
      anterior hyaloid disruption with a 22-gauge needle, in addition to medical
      management maintained IOP in the normal range until anterior vitrectomy could be
      performed. After vitrectomy, glaucoma resolved and medical treatment was no
      longer necessary.

PMID- 12071867
TI  - An improved DNA-based test for detection of the codon 616 mutation in the alpha
      cyclic GMP phosphodiesterase gene that causes progressive retinal atrophy in the
      Cardigan Welsh Corgi.
AB  - The aim of the study was to develop an improved test to detect the codon 616 gene
      mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive
      retinal atrophy in the Cardigan Welsh Corgi. We studied 10 control dogs of known
      genotype at codon 616 of the alpha cyclic GMP phosphodiesterase gene and 80
      Cardigan Welsh Corgis of unknown genotype. A polymerase chain reaction (PCR)
      utilizing a mismatched primer was designed so that it introduced a HinfI
      restriction enzyme digestion site into the PCR product only if the normal gene
      sequence was present, the restriction site was not introduced if the codon 616
      mutation was present. An additional HinfI site present in the amplified section
      from both normal and mutant alleles acted as a positive control for restriction
      enzyme digestion. The PCR reliably amplified a portion of the alpha cyclic GMP
      phosphodiesterase gene spanning the codon 616 mutation site. Restriction enzyme
      digestion with HinfI and analysis on a suitable agarose gel reliably ascertained
      the genotype of the control dogs and was used to identify the genotype of a
      further 80 test dogs. An improved DNA-based test for detection of the codon 616
      mutation in the alpha cyclic GMP phosphodiesterase gene that causes progressive
      retinal atrophy in the Cardigan Welsh Corgi has been designed. This overcomes
      potential problems that could be associated with allele-specific PCR tests such
      as that used previously in a diagnostic test for this gene mutation.

PMID- 12071868
TI  - Effects of topical 0.5% tropicamide on intraocular pressure in normal cats.
AB  - The objective of the study was to determine the effect of topical 0.5%
      tropicamide on intraocular pressure (IOP) in normotensive feline eyes. IOP was
      measured bilaterally in 70 clinically healthy cats and gonioscopy (and
      goniophotography) was performed. Thereafter, 50 cats were treated unilaterally
      with one drop of 0.5% tropicamide. The contralateral, left eye served as a
      control. In the placebo group consisting of 20 cats, one drop of physiologic
      saline solution was administered to the right eye. In all cats, IOP of both eyes
      was measured 30, 60 and 90 min after topical administration. After unilateral
      tropicamide application, IOP increased significantly both in the right and in the
      left eye. Maximum average IOP increase was observed at the control measurement
      performed 90 min after treatment, with an elevation of 3.8 +/- 4.2 mmHg in the
      right eye and 3.5 +/- 3.6 mmHg in the left eye. Maximum IOP increase after
      treatment was 18.0 mmHg in the treated eye and 17.0 mmHg in the left eye.
      Measurements made at 60 min after treatment revealed a significantly higher
      increase in IOP in the right eye as compared to the left eye (P60 < 0.05),
      whereas the differences between right and left eye in IOP increase were not
      significant at 30 and 90 min after mydriatic application (P30 = 0.123; P90 =
      0.305). Although tropicamide-induced mydriasis was observed in the treated eye,
      the contralateral eye did not show any changes in pupillary function at any time.
      With increasing age of the cats, IOP increase was found to be more moderate,
      whereas the gender of the cats did not have any significant influence on IOP
      changes. In the 20 cats in the placebo group, no significant changes in IOP were
      observed. We conclude that topical 0.5% tropicamide causes a significant
      elevation of IOP in the treated and untreated eye in normal cats.

PMID- 12071869
TI  - Canine choroidal melanoma with metastases.
AB  - A 3-year-old-female, spayed Golden Retriever was examined for a unilateral
      retinal detachment with exophthalmos. Ultrasonographically, a mass was detected
      with intra- and extraocular extension. The orbit was exenterated and the dog
      recovered uneventfully. Histopathologic diagnosis was a primary choroidal
      melanoma with orbital extension, however, the behavioral and cytologic features
      were benign. Routine examinations postsurgically were nonremarkable. Twenty-one
      months after surgery the dog was euthanized for respiratory collapse with
      radiographic signs of metastasis. Necropsy revealed black lesions in the lung and
      liver. Histopathologic diagnosis was metastatic melanoma with morphology and
      behavior identical to the primary choroidal melanoma. This is the first
      definitive case of a canine choroidal melanoma with metastasis.

PMID- 12071870
TI  - Subconjunctival filariasis due to Onchocerca sp. in dogs: report of 23 cases in
      Greece.
AB  - In the present study, we describe a series of 23 cases of ocular subconjunctival
      parasitic granulomas in dogs, admitted to the Clinic of Surgery, Faculty of
      Veterinary Medicine of the Aristotle University of Thessaloniki, Greece, between
      1997 and 2000. The ophthalmic manifestations in all animals were periorbital
      swelling, discomfort, photophobia, conjunctival congestion, and discharge. A more
      detailed examination revealed the presence of periocular masses (nodules) on the
      subconjunctival bulbar space. Granulomatous or cyst-like formations were
      extracted surgically, and were found to contain thread-like nematode parasites. A
      histologic and parasitologic examination of tissues and parasites was carried
      out. Diagnosis of parasitic granulomas was made and the parasite was identified
      as Onchocerca sp. This is the largest series of cases reported of aberrant
      Onchocerca infections in dogs coming from one geographic location.

PMID- 12071871
TI  - Effects of anti-inflammatory drugs and preservatives on morphologic
      characteristics and migration of canine corneal epithelial cells in tissue
      culture.
AB  - OBJECTIVE: To determine the effects of commonly used ophthalmic corticosteroids,
      suprofen, polysulfated glycosaminoglycan and preservatives on morphologic
      characteristics and migration of canine corneal epithelium grown in cell culture.
      ANIMALS STUDIED: Corneal epithelial cells harvested from the corneas of
      euthanized dogs were propagated in cell culture. PROCEDURES: Canine corneal
      epithelium was grown in tissue culture. The cells were treated with different
      corticosteroids, polysulfated glycosaminoglycan, suprofen or preservatives at
      different concentrations after a defect was created in the monolayer. Cellular
      morphologic characteristics and closure of the defect were compared between test
      drugs and controls. RESULTS: Morphologically the cells treated with dexamethasone
      were essentially the same as controls. Prednisolone and hydrocortisone caused
      rounding and shrinkage of the cells. Both suprofen and polysulfated
      glycosaminoglycan caused no apparent changes in morphologic characteristics at
      the lowest concentrations tested, but at higher concentrations there was a
      concentration-dependent degree of rounding and shrinkage. Benzylkonium chloride
      and thimerosal caused rounding and shrinkage of all the cells at all
      concentrations tested. Dexamethasone, hydrocortisone, and suprofen did not
      inhibit epithelial migration over the defects at the lowest concentrations
      tested. All other drugs and concentrations inhibited cellular migration.
      CONCLUSION: Dexamethasone affected the morphologic characteristics and migration
      of corneal epithelial cells less than hydrocortisone and prednisolone; therefore,
      dexamethasone may be the drug of choice when a corticosteroid is indicated and an
      epithelial defect is present. Suprofen and polysulfated glycosaminoglycan caused
      a concentration-dependent effect on morphologic characteristics and migration.
      The preservatives caused severe changes and inhibited migration of the canine
      corneal epithelial cells at all concentrations and may therefore contribute to
      poor epithelialization of ulcers treated with preservative-containing drugs.

PMID- 12071872
TI  - Bilateral proliferative keratitis in a Domestic Long-haired cat.
AB  - A 9-year-old, female spayed, Domestic Long-haired cat was presented with
      bilateral, progressive, pink-white corneal opacities. The referring veterinarian
      had diagnosed feline herpesvirus-1 (FHV-1) keratitis though diagnostics for FHV-1
      had not been performed and treatment with antibiotics and antivirals did not
      improve the condition. Histopathology showed neutrophils, plasma cells and
      lymphocytes, but no eosinophils or mast cells. Routine diagnostics did not find
      an underlying cause, but Southern blot analysis for FHV-1 was positive. The cat
      responded to topical corticosteroids and cyclosporine when used consistently.

PMID- 12071873
TI  - Study of five cell salvage machines in coronary artery surgery.
AB  - We evaluated the effectiveness, ease of use and safety of five machines for blood
      salvage during coronary artery surgery. All were equally effective in
      concentrating red cells. We measured haemoglobin, packed cell volume, free
      haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin
      complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d
      dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed
      cell suspensions and in a unit of bank blood prepared for each patient. All
      machines were equally safe and easy to use and were equally effective in removing
      heparin and the physiological components measured. There were no adverse effects
      on patients. Clotting factors are severely depleted both in salvaged blood, even
      before washing, and in bank blood. Cell savers are a valuable adjunct to coronary
      artery surgery, but careful monitoring of coagulation is required when the
      volumes of either bank blood or salvaged blood are large.

PMID- 12071874
TI  - Limited efficacy of universal leucodepletion in reducing the incidence of febrile
      nonhaemolytic reactions in red cell transfusions.
AB  - This article demonstrates a 62% reduction in the number of febrile nonhaemolytic
      transfusion reactions (FNHTRs) and 50% reduction in febrile reaction rate
      associated with red cell transfusions following graded introduction of universal
      leucodepletion. Though this is a statistically significant reduction (P = 0.009),
      it shows limited efficacy in abrogating this complication. We also found a
      reduction in the proportion of cases of FNHTRs with lymphocytotoxic antibodies
      over the period studied from 54% in 1998, 28% in 1999 to 23% in 2000. This
      corresponds to a relative increase in the number of febrile reactions without
      human leucocyte antigen (HLA) antibodies following full implementation of
      universal leucodepletion, as the total number of reported reactions actually fell
      considerably during the period. The increase in the number of cases without HLA
      antibodies was directly proportional to the increase in the number of
      leucodepleted units used.

PMID- 12071875
TI  - National audit of citrate toxicity in plateletpheresis donors.
AB  - Citrate toxicity complicating plateletpheresis is not uncommon. However, the
      scale and severity of the problem have never been formally addressed. In order to
      answer these questions we undertook a national audit of 13 070-platelet
      procedures throughout 17 apheresis centres in England over a 3-month period from
      1 April to 30 June 2000. A standard form was distributed to each centre to record
      the symptoms/signs of citrate toxicity which were then graded (grades 1-5)
      according to their severity. The following variables were studied to determine
      whether they influenced the frequency and severity of citrate toxicity: 1. The
      type of manufacturer's cell separator used (Cobe Spectra, Haemonetics, Baxter
      Amicus and Trima). 2 The type of procedure: single needle, dual needle, single,
      double or triple dose. 3 The way in which donors were instructed to report
      symptoms of citrate toxicity. OUTCOME: Plateletpheresis is a relatively safe
      procedure provided that donors who experience severe reactions receive
      appropriate treatment. The incidence of severe citrate toxicity (0.03%
      procedures) is comparable to that of severe faints following whole blood
      donation, indicating a comparable margin of safety. Donors should be warned of
      the symptoms of citrate toxicity at their first attendance only. More frequent
      reminders encourage donors to over-report symptoms of mild citrate toxicity.

PMID- 12071876
TI  - Heparin-induced thrombocytopenia: detection of antiheparin/PF4 antibodies by
      means of heparin/PF4-coated beads and flow cytometry.
AB  - A total of 70 serum samples from heparin-induced thrombocytopenia (HIT II)
      patients, non-HIT patients and healthy subjects, respectively, were studied for
      the presence of antiheparin/PF4 antibodies. Two enzyme-linked immunosorbent assay
      (ELISA) assays were compared with the particle gel immunoassay (PaGIA). Beads of
      the PaGIA kit were also used to evaluate the feasibility of flow cytometric
      detection of antiheparin/PF4 antibodies in patient samples. Experiments have
      shown that all samples found positive by ELISA and PaGIA, were also positive when
      analysed by flow cytometry by an indirect test using the high-density particles
      coated with heparin/PF4 complexes and a second step fluorescein isothiocyanate
      (FITC) antihuman immunoglobulin (Ig)G reagent. The procedure was easy to perform,
      repetitive and beads were promptly visualized by physical parameters, with a very
      low background. In conclusion, the results of this study suggest that flow
      cytometry is a reliable method for the detection of antiheparin/PF4 antibodies.

PMID- 12071877
TI  - Gene frequencies of human platelet antigens 1-5 in indigenous Australians in
      Western Australia.
AB  - The frequencies of human platelet antigen (HPA) systems vary between different
      racial groups; however, HPA frequency data for some racial groups are still
      incomplete. We report the distribution of HPA 1-5 systems in Australian
      Aborigines from a remote community in the north-west of Australia and compare our
      findings with HPA observed in a Western Australian blood donor population. Using
      a polymerase chain reaction (PCR) with sequence-specific primers, 185 indigenous
      Australians and 1000 Western Australian blood donors were genotyped for each of
      the HPA 1-5 systems. Comparison of gene frequencies of alleles from HPA-1, -2, -3
      and -5 systems showed significant differences between Aboriginal people and
      Western Australian blood donors (P < 0.001). In particular, the frequency of HPA
      3b (0.068) in the Australian Aboriginals, from this study, was one of the lowest
      reported, whilst the frequency of HPA-5b (0.246) was one of the highest for this
      allele. Gene frequencies were similar to those reported for central Australian
      Aborigines but with no other ethnic group. In conclusion, this study confirms
      significant differences in HPA distributions between indigenous Australians,
      Australian blood donors and other racial groups. These results indicate a higher
      potential risk of alloimmunization to HPA-1, -2 and -3 in Australian Aborigines
      receiving transfusion therapy from a Caucasian blood donor population, thereby
      having practical implications for transfusion and pregnancy risks in people of
      Aboriginal origin.

PMID- 12071878
TI  - In vitro RBC exposure to Plasmodium falciparum has no effect on RBC antigen
      expression.
AB  - Severe malarial anaemia is a leading cause of death in African children younger
      than 3 years of age who are infected with Plasmodium falciparum. The pathogenesis
      of this anaemia is not understood. The purpose of this study was to determine if
      P. falciparum induces changes in RBC membranes that contribute to the immune
      destruction of RBCs. RBCs were collected from healthy subjects and tested using
      standard haemagglutination assays for 45 antigens representing 21 blood group
      systems/collections before and after exposure to P. falciparum, strain FVO.
      Lectins were used to determine whether crypt or neoantigens were expressed on the
      RBC membrane. Polybrene was used to detect changes in sialic acid. RBCs were
      cultured in vitro with and without the parasite, and blinded serologic studies
      were completed. CD35 (complement receptor 1), CD55 (decay-accelerating factor),
      CD59 (membrane inhibitor of reactive lysis) and CD47 (integrin-associated
      protein) flow cytometric assays were compared for infected and uninfected RBCs.
      The percentage of parasitaemia was determined using Giemsa-stained thin blood
      films. Two (Ch, Lub) of the 45 antigens had differing strengths of agglutination
      between infected and uninfected RBCs, but these differences were resolved with a
      second source of antisera. Forty-three antigens showed no significant differences
      in the strength of agglutination between the infected and uninfected RBCs. Lectin
      and polybrene testing showed no differences. CD35, CD55, CD59 and CD47 levels
      showed no significant differences. P. falciparum does not appear to alter the
      expression of classified immunogenic antigens on the RBC membrane in this in
      vitro system. The pathogenesis of the haemolytic episode that occurs in these
      children remains unclear.

PMID- 12071879
TI  - Clinical significance of anti-G.

PMID- 12071880
TI  - Platelet chemokines.

PMID- 12071884
TI  - Scanning electron microscopic changes of the canine uterine luminal surface
      during oestrus and late metoestrus.
AB  - In this study the endometrial morphology of four dogs in oestrus and 10 dogs in
      late metoestrus was investigated with scanning electron microscopy. In early
      oestrus the cells were slightly convex with fairly long microvilli and cell
      boundaries that were apparent but situated on a deeper level than the cell
      surface. In late oestrus the cells were clearly convex with long and numerous
      microvilli masking the cell boundaries. At the beginning of late metoestrus the
      cells became less convex with many but short microvilli and prominent but lower
      situated cell boundaries. At the end of late metoestrus the cells were flat with
      very short microvilli and protruding cell borders. These morphological findings
      were correlated with the cyclic variations of the steroid hormone levels.

PMID- 12071885
TI  - Assessment of different sperm quality parameters to predict in vitro fertility of
      bulls.
AB  - Frozen-thawed semen from six bulls with high (> 60%) and low (20-35%) in vitro
      fertility was used for studying the predictive value of simple sperm quality
      tests with respect to in vitro fertilization (IVF) outcome as assessed by
      pronucleus (PN) formation ability. Sperm quality parameters, such as sperm
      concentration, motility, progressive motility, live-dead sperm ratio, morphology,
      membrane integrity, mitochondrial activity and acrosomal status were analysed
      using both conventional and automatic techniques at three time points during the
      IVF process, namely after sperm thawing, Percoll differential gradient
      centrifugation and IVF. Associations between the sperm quality parameters before
      and after IVF, and PN formation ability were assessed by using linear regression
      analyses. The percentages of motility, progressive motility and normal morphology
      determined after sperm thawing, and the percentage of live spermatozoa assessed
      after Percoll preparation by using nigrosin-eosin (N-E) staining showed a good
      correlation with PN formation ability, but the regression parameters were
      borderline not significant. These parameters formed the most reliable basis for
      predicting IVF outcome. After IVF, the percentage of live spermatozoa determined
      by using N-E staining was the only sperm quality parameter showing a significant
      association with the PN formation ability of a given bull. This sperm quality
      test can be used as a non-invasive method to estimate the PN formation ability of
      oocytes which are further cultured to assess embryonic development.

PMID- 12071886
TI  - Embryonic signals and survival.
AB  - The objective of this review is to give an overview of the signaling mechanisms
      between the conceptus and the mother before implantation. The interactions
      between the embryo and uterus are complex and essential for normal embryo
      development and implantation. Problems in the signaling mechanisms are thought to
      play a significant role in early embryonic mortality since a high rate of
      embryonic morality occurs during this period. This review will focus on the
      mechanisms involved in the development of the conceptus and the prevention of
      luteolysis. It is based primarily on what is known in ruminants but also refers
      to work in other species such as the mouse and primates.

PMID- 12071887
TI  - Formation of a reservoir of sperm in the oviduct.
AB  - A reservoir of sperm in the initial segment of the oviduct has been found in
      several species of domestic and laboratory mammals. Evidently, the reservoir
      serves to ensure successful fertilization by providing the appropriate number of
      sperm in the appropriate physiological state for fertilizing oocytes soon after
      they enter the oviduct. Recent evidence indicates that sperm are trapped in the
      reservoir by binding to specific carbohydrate moieties on the surface of the
      mucosal epithelium of the oviduct. A bovine seminal plasma protein has been
      identified that associates with sperm and confers on them the capacity to bind to
      the carbohydrate moiety.

PMID- 12071888
TI  - Function of the cumulus oophorus before and during mammalian fertilization.
AB  - CONTENTS: Fertilization encompasses a series of different steps which have to be
      performed in a well-orchestrated way to create a new individual. They include
      sperm capacitation, sperm binding and penetration of the zona pellucida,
      traversing the perivitelline space, binding and fusion with the oolemma,
      activation of the oocyte and decondensation of the sperm head to form the male
      pronucleus. In most mammalian species, cumulus cells surround the oocyte at the
      time of fertilization. Removal of the cumulus oophorus at this point of time
      often leads to a drop in fertilization rates. It is not yet known how cumulus
      cells interact with the oocyte or with spermatozoa to promote fertilization.
      There are different possibilities: 1 cumulus cells cause mechanical entrapment of
      spermatozoa and guide hyperactivated spermatozoa towards the oocyte, while
      preventing abnormal spermatozoa to enter the cumulus matrix; 2 cumulus cells
      create a micro-environment for the spermatozoa which favours their capacitation
      and penetration into the oocyte; 3 cumulus cells prevent changes in the oocyte
      which are unfavourable for normal fertilization; these changes can be located in
      the zona pellucida or in the cytoplasm. In this review, studies in several
      species are listed to prove the importance of these three cumulus cell functions
      and the current lines of research are highlighted. Moreover, different ways to
      improve in vitro fertilization of bovine cumulus-denuded oocytes are discussed.

PMID- 12071889
TI  - Is mechanically induced cystic endometrial hyperplasia (CEH) a suitable model for
      study of spontaneously occurring CEH in the uterus of the bitch?
AB  - CONTENTS: Cystic endometrial hyperplasia (CEH) was experimentally reproduced by
      the intraluminal insertion of a silk wire in the uterus of metestral bitches to
      obtain a model for the study of spontaneously occurring CEH in the bitch. This
      mechanically reproduced CEH corresponded histologically very well to
      spontaneously occurring CEH. With respect to sex hormone receptor expressions,
      however, there was no similarity. In the mechanically induced CEH, progesterone
      receptor expression was reduced in the epithelial cells (surface epithelium and
      endometrial glands) and slightly increased in the stromal fibroblasts and
      myometrium as compared with the normal metestrus uterus. The oestrogen receptor
      expression in mechanically induced CEH was reduced in the epithelial cells
      (surface epithelium and endometrial glands) and more or less unchanged in the
      stromal fibroblast and myometrium as compared with the normal metestrus uterus.
      This is in contrast to the increased sex hormone receptor expressions in all
      uterine cell types, observed in spontaneously occurring CEH. The mechanically
      induced CEH model corresponds immunohistochemically more to early placentation
      and to pyometra in the bitch. Thus this experimental CEH model is not suitable
      for pathogenic studies of spontaneously occurring CEH in the bitch.

PMID- 12071890
TI  - Use of the Sperm Quality Analyzer (SQA II-C) for the assessment of dog sperm
      quality.
AB  - In the present study, an automated system for sperm analysis, the Sperm Quality
      Analyzer (SQA II-C), was tested as a potential tool for the assessment of dog
      sperm quality. In the first experiment the device displayed a good repeatability
      of measurements for semen of medium and high quality, as evidenced by a low
      coefficient of variance (CV; 0.08), whereas a high CV (0.46) was obtained for one
      dog with semen of inferior quality. In the second experiment, seven different
      sperm concentrations (25-300 x 106/ml), obtained by dilutions in Hepes-TALP
      medium were stored for 48 h at room temperature. A concentration dependent
      increase in sperm motility index (SMI) was shown, reaching a plateau at 150 x 106
      spermatozoa/ml. For all sperm concentrations, the SMI value decreased
      significantly after 24 h, indicating the importance of sperm motility for SMI
      values. For sperm concentrations lower than 150x106/ml, highly significant
      correlations [r=0.80;p<0.05] were established between SMI values on one hand and
      sperm concentration, and semen parameters expressing the overall semen sample
      quality on the other hand (experiment 3) while non-significant or low
      correlations were found between SMI values and other individual sperm parameters.
      In experiment 4, significantly high correlations (r=0.97) were found between mean
      SMI values and post-thaw motility and progressive motility assessed subjectively.
      In conclusion, our study indicates that both motility and concentration largely
      influence SMI values and that the SQA II-C saturates at 150 x 106 fresh
      spermatozoa/ml. In our opinion, the SQA II-C may be a useful and objective device
      to assess the post-thaw motility of dog sperm.

PMID- 12071891
TI  - Cell-specific distribution of progesterone receptors in the bovine ovary.
AB  - This study describes the localization of progesterone receptors (PR) in the
      bovine ovary. Ovaries were obtained from 11 non-pregnant and two pregnant cows.
      Progesterone receptors were visualized by immunohistochemistry on paraffin
      sections. Nuclear staining for PR was observed in cells of the follicles, corpora
      lutea, theca layers, surface epithelium, tunica albuginea, and in superficial and
      deep stroma cells. No staining was noticed in apoptotic bodies of atretic
      follicles. Expression of PR in follicle cells indicates an intrafollicular role
      of progesterone. The higher expression in thecal cells compared with follicle
      cells indicates that thecal cells mediate some effects of progesterone on the
      follicular development. Superficial stroma cells showing high expression might
      have a similar influence on primordial and primary follicles. In general, luteal
      cells had a lower expression than follicle cells, which may be explained by the
      down-regulatory effect of locally produced progesterone. The lower expression in
      luteal cells during pregnancy can be due to the longer life span of this corpus
      luteum and concomitant degeneration of its PR. The high and rather constant
      expression of PR in cells of the surface epithelium remains to be elucidated.

PMID- 12071892
TI  - Insemination of susceptible heifers with semen from a non-viraemic bull with
      persistent bovine virus diarrhoea virus infection localized in the testes.
AB  - Bulls shedding bovine viral diarrhoea virus (BVDV) in semen and simultaneously
      having a high concentration of circulating antibodies may cause reproductive
      problems and spread the viral infection within cattle populations. To investigate
      this in detail, three heifers were inseminated with BVDV-infected semen from a
      non-viraemic, seropositive Holstein-Friesian bull, named 'Cumulus'. One control
      heifer was inseminated with semen from a healthy bull that was free of BVDV. All
      four heifers remained clinically healthy throughout the experiment. The
      conception succeeded in the control animal and in two of the three heifers
      inseminated with semen containing BVDV. The heifer with the failed conception was
      the only one that became systemically infected with BVDV. This animal was deemed
      non-pregnant by ultrasonic examination on day 34 after insemination and showed no
      signs of subsequent oestrus during the entire experimental period. At slaughter,
      42 days after insemination, there were no histopathological changes in the
      ovaries and virus was not detected in ovarian tissue. The fact that seronegative
      dams served with semen from persistently infected bulls have occasionally
      produced persistently infected calves together with the present findings and the
      fact that non-viraemic, seropositive bulls can constantly shed BVDV, suggest that
      the use of semen from such bulls in BVDV-free herds could have far-reaching
      consequences, especially if it led to the birth of persistently infected (P1)
      calves.

PMID- 12071893
TI  - Blood and intrauterine leukocyte profile and function in dairy cows that
      spontaneously recovered from postpartum endometritis.
AB  - The profile and function of blood and uterine leukocytes were evaluated in 14
      dairy cows that spontaneously recovered from postpartum endometritis (mild, n=6
      and heavy, n=8; general health not affected). From a minimum of 2 weeks before
      parturition until 6 weeks postpartum, blood samples were obtained twice weekly
      for leukocyte counts and leukogram determination and once weekly for flow
      cytometry assessment of polimorphonuclear neutrophils (PMN) phagocytic capacity
      and oxidative burst activity. Uterine fluid-stained smears, obtained twice weekly
      from parturition until fluid was present in the uterus, were used for
      determination of the percentage of PMN, of phagocytizing PMN (phago-PMN) and of
      the mean number of phagocyted bacteria per phagocytizing PMN (phagocytic index;
      PI). Uterine swabs were obtained twice weekly from parturition until 35 days
      postpartum for bacteriological examination. The time of endometritis diagnosis
      was similar in cows with mild or heavy endometritis but the latter cows had a
      significantly longer persistence of the infection and of the isolation of Gram
      negative anaerobes from the uterus. However, the effect of group (mild versus
      heavy) was not significant for all the blood and uterine parameters analysed. The
      effect of sampling day (within group effect) was significant (p<0.01 to
      p<0.00001) for all parameters, except for the blood monocyte count and the blood
      PMN phagocytic capacity, in which only a tendency for significance was observed
      (p<0.1). The effect of the interaction group x sampling day was significant only
      for the blood monocyte count. The phago-PMN and the PI were significantly
      correlated (r=0.70, p<0.001). A significant correlation was also observed between
      the uterine fluid phago-PMN and the blood PMN oxidative burst activity (r=-0.41,
      p<0.05). At the spontaneous recovery, the blood PMN oxidative burst activity was
      significantly higher (p<0.05) and the percentage of intrauterine phago-PMN and
      the PI were significantly lower (p<0.001 and p<0.01, respectively) than at
      diagnosis of endometritis. These results suggest that a decrease in blood PMN
      oxidative burst activity until the first week postpartum could be associated with
      an increased susceptibility to early postpartum endometritis. The later increase
      in this parameter as well as the increase in the intrauterine fluid phago-PMN and
      PI, might favour the spontaneous resolution of endometritis.

PMID- 12071894
TI  - Correlation between the cell number and diameter in bovine embryos produced in
      vitro.
AB  - This study was designed to examine the effects of age and developmental stage of
      in vitro-produced bovine embryos on the cell number of the embryos and to
      investigate the correlation between the cell number and diameter in the embryos.
      The diameter and cell number in blastocysts and expanded blastocysts collected on
      days 7-9 after in vitro fertilization (IVF) were examined. Although the diameters
      of the blastocysts collected on days 7 and 8 after IVF were smaller than those of
      the expanded blastocysts collected on day 9, the cell number in both types of
      embryos was similar. The cell numbers of the blastocysts and expanded blastocysts
      decreased with increasing embryo age. There were positive correlations between
      the cell number and diameter in bovine embryos at each stage collected on each
      day after IVF. However, the value of the correlation coefficient in the day-9
      expanded blastocyst group tended to be higher than that in the other groups.
      These results indicate that the cell number of in vitro-produced embryos is
      affected by the embryonic stage and age. The diameter of the embryo may be
      potentially used for the viability testing of the expanded blastocysts collected
      on day 9 after IVF.

PMID- 12071895
TI  - Silent voices.

PMID- 12071896
TI  - Interdisciplinary collaboration: a study in progress.
AB  - A multidisciplinary, multi-institutional collaborative effort was initiated to
      address the perspectives of health care literacy in an urban/rural area of west
      Texas. This article presents the mechanisms utilized in the development and
      implementation of this collaborative process. Individuals within multiple
      institutions realized the importance of working together to address health care
      issues. As a result of this consortium development, an initial endeavor
      addressing health care literacy and functional health status was initiated. The
      development of the consortium and the project is presented in this article to
      provide a model for consortium development applicable to other professions.

PMID- 12071897
TI  - The role of the nurse on a transdisciplinary early intervention assessment team.
AB  - Assessing young children with disabilities is a complex process requiring the
      expertise of a team of professionals from several disciplines. Team members often
      include the child's family members, early childhood special educators, clinical
      psychologists, speech-language pathologists, social workers, physical and
      occupational therapists, pediatricians, and nurses. A team approach meets
      standards of best practice in early childhood intervention and encourages full
      family participation in the assessment process. This article explores the process
      of team building, role release through a transdisciplinary approach, and a
      nurse's role on a transdisciplinary assessment team.

PMID- 12071898
TI  - Health care delivery system influences changes in nursing educational materials.
AB  - The changing health care delivery system has affected nursing care delivery
      models. To meet the needs of these shifting sands, health-related professions
      must examine curricula preparing new graduates. An exploratory, descriptive
      survey design was employed to discover motivators for and types of curricular
      changes occurring in nursing programs and determine what supportive educational
      materials are needed. One hundred sixty-seven (26%) of the 651 surveys mailed to
      a sample of the whole of U.S. baccalaureate nursing programs were returned.
      Relationships between and among categories of nominal data culled from the
      participants' experiences were compared using nonparametric statistics. Findings
      demonstrated why and what changes were made and what educational materials are
      needed to support new curricula. Results also indicated that blurring of
      boundaries between community and general acute care nursing is necessary, and
      changes throughout curricula, including educational materials, must reflect the
      real-life community aspects of the health care needs of all individuals.

PMID- 12071899
TI  - An interactive technology approach to educate older adults about drug
      interactions arising from over-the-counter self-medication practices.
AB  - An interactive computer program (Personal Education Program [PEP]) designed for
      the learning styles and psychomotor skills of older adults was used to teach
      older adults about potential drug interactions that can result from self
      medication with over-the-counter (OTC) agents and alcohol. Subjects used the PEP
      on notebook computers equipped with infrared sensitive touchscreens. Subjects
      were recruited from senior centers. Those who met age, vision, literacy,
      independence, and medication use criteria were randomly assigned to one of three
      groups: (1) PEP plus information booklet; (2) information booklet only; or (3)
      control. A repeated measures (three time periods 2 weeks apart), three-group
      design was used. Users of PEP had significantly greater knowledge and self
      efficacy scores than both the conventional and control groups at all three time
      points. The PEP group reported fewer adverse self-medication behaviors over time.
      Reported self-medication behaviors did not change over time for either the
      conventional or control groups. Subjects indicated a high degree of satisfaction
      with the PEP and reported their intent to make specific changes in self
      medication behaviors.

PMID- 12071900
TI  - Factors associated with breast self-examination among jordanian women.
AB  - The purpose of this cross-sectional, correlational, descriptive study was to
      investigate factors and beliefs that may be related to the practice of breast
      self-examination (BSE) among a group of Jordanian women. The sample consisted of
      519 women from two major universities in Jordan. About 36% of the sample were
      university employees and 64% were graduate and undergraduate students. Stratified
      random sampling was used to enroll the undergraduate students while graduate
      students and employees were selected by convenience sampling. The study
      instrument was an adapted version of Champion's Revised Health Belief Model Scale
      (CRHBMS). The results were analyzed using a chi-square test and a stepwise
      multiple regression. The main findings indicate that although the majority of the
      sample population (67%) had heard/read about BSE, only a quarter of them reported
      that they had ever practiced BSE in the previous 12 months, and only 7% had
      performed it on a regular monthly basis. Confidence, motivation, susceptibility,
      and fewer barriers were variables that showed a positive association with BSE
      practice in the previous year, while benefits, susceptibility, and motivation
      influenced the intention to perform BSE in the future. Women's age, level of
      education, having heard or read about breast tumors, and personal history of
      breast tumors were also found to be significant predictors of BSE practice.

PMID- 12071901
TI  - Effects of respite care for children with developmental disabilities: evaluation
      of an intervention for at risk families.
AB  - Respite child care programs that provide temporary child care, support, and
      referral services to families of children with developmental disabilities are
      thought to be a critical component of formal social support interventions deemed
      necessary to promote healthy family functioning and prevent child maltreatment.
      This study describes sociodemographic characteristics, parenting stress levels,
      foster care placement, and founded child maltreatment rates in families of
      children with developmental disabilities who were using respite care services in
      a rural Midwestern state. Comparison of matched pre- and post-test Parenting
      Stress Index scores indicated significant decreases in Total Stress scores
      (t=3.27, df=86, p=0.0016), Parent Domain scores (t=3.55, df=86, p=0.0006), and
      Child Domain scores (t=2.2, df=86, p=0.02) following provision of respite care.
      Through logistic regression, it was determined that life stress, social support,
      and service level were significantly related to the occurrence of child
      maltreatment during enrollment ( p < 0.05). The investigator suggests that public
      health nurses can enhance their case management strategies when working with the
      parents of children with developmental disabilities by monitoring for caregiver
      burnout in addition to ensuring that the child is receiving care appropriate for
      his or her level of need.

PMID- 12071902
TI  - Learning to be a normal mother: empowerment and pedagogy in postpartum classes.
AB  - This qualitative study, which was conducted in the summer of 1992, presents the
      findings of how six first-time mothers and two public health nurses experienced
      pedagogical practices within postpartum classes offered by two public health
      units in Ontario, Canada. How concerns and aspirations of new mothers were
      constructed and mediated in the postpartum class are analyzed using concepts from
      poststructuralist and feminist methodologies. This study goes beyond an analysis
      of individual teaching and learning styles and discusses how social structures of
      isolation, investment in a medical discourse, and processes of normalization
      construct an individual's experiences and practices of mothering, which in turn
      influence pedagogical practices in postpartum classes. Issues of empowerment,
      language, support, and knowledge exchange are discussed.

PMID- 12071903
TI  - Health-promoting behaviors of elderly korean immigrants in the United States.
AB  - The purpose of this study was to explore health-promoting behaviors among elderly
      Korean immigrants, and to examine the relationships of their health-promoting
      behaviors with self-efficacy and perceived health status. One hundred ten elderly
      Korean immigrants residing in the United States were interviewed using a
      structured questionnaire. The mean score of health promoting behaviors of elderly
      Korean immigrants was 2.54 on the 5-point Likert scale. Nutrition was the
      subdomain with the highest mean score (M=3.01) and exercise was the subdomain
      with the lowest mean score (M=1.92). Both self-efficacy (r=0.49, p=0.01) and
      perceived health status (r=0.19, p=0.043) were significantly related to health
      promoting behaviors. Education (F=3.61, p=0.016) and economic status (F=3.01,
      p=0.034) were significantly associated with health-promoting behaviors. This
      study showed poor practices of healthy lifestyles of elderly Korean immigrants.
      Low exercise scores indicated the need for community based exercise and health
      promotion programs for the elderly Korean immigrants population.

PMID- 12071905
TI  - The advent of high-tech home care in Germany.
AB  - The purpose of this conceptual paper is to examine the current situation in which
      high-tech home care is going to materialize in Germany in the beginning of the
      new millennium. It will be shown that there have been long-standing efforts to
      bring about a corresponding expansion of home care as can be observed in other
      countries (e.g., United States). It is apparent, however, that these efforts are
      still crowned by only modest success. This especially applies to high-tech home
      care. The introduction of this special form of care is turning out to be a
      complicated process on a collision course with a great number of obstacles due to
      the peculiarities of Germany's health care system. If the nursing options related
      to high-tech home care are to be opened up and put into practice in the future,
      numerous prerequisites for their development will first have to be created. From
      a public health nursing viewpoint the three most pressing issues on the list of
      priorities relevant to high-tech home care are to: (1) increase awareness of the
      problems associated with this special form of care; (2) eliminate the present
      information deficits in society; and (3) initiate a debate in Germany about
      possibilities and limitations of technology-intensive home care, building on
      international exchange of experiences and ideas.

PMID- 12071904
TI  - Mapping the future of environmental health and nursing: strategies for
      integrating national competencies into nursing practice.
AB  - :Nurses are increasingly the primary contact for clients concerned about health
      problems related to their environment. In response to the need for nursing
      expertise in the field of environmental health, the Institute of Medicine (IOM),
      Agency for Toxic Substances and Disease Registry (ATSDR), and National Institute
      of Nursing Research (NINR) have designed core competencies for the nursing
      profession. The IOM competencies focus on four areas: (1) knowledge and concepts;
      (2) assessment and referral; advocacy, ethics, and risk communication; and (4)
      legislation and regulation. The competencies establish a baseline of knowledge
      and awareness in order for nurses to prevent and minimize health problems
      associated with exposure to environmental agents. To address the known
      difficulties of incorporating new priorities into established practice, nurses
      attending an environmental health short course participated in a nominal group
      process focusing on the question, "What specific actions can we take to bring
      environmental health into the mainstream of nursing practice?" This exercise was
      designed to bring the concepts of the national initiatives (IOM, NINR, ATSDR) to
      the awareness of individual nurses involved in the direct delivery of care.
      Results include 38 action items nurses identified as improving awareness and
      utilization of environmental health principles. The top five ideas were: (1) get
      environmental health listed as a requirement or competency in undergraduate
      nursing education; (2) improve working relationships with interdepartmental
      persons-a team approach; (3) strategically place students in essential
      organizations such as NIOSH, ATSDR, or CDC; (4) educate nurse educators; and (5)
      create environmental health awards in nursing. The 38 original ideas were also
      reorganized into a five-tiered conceptual model. The concepts of this model
      include: (1) developing partnerships; (2) strengthening publications; (3)
      enhancing continuing education; (4) updating nursing practice; and (5)
      strengthening schools of nursing. The model serves as a road map for action in
      building environmental health capacity within mainstream nursing.

PMID- 12071906
TI  - Saving the practice--top 10 unfinished issues to inform the nursing debate in the
      new millennium.

PMID- 12071907
TI  - The history of nursing in the home: revealing the significance of place in the
      expression of moral agency.
AB  - The history of nursing in the home: revealing the significance of place in the
      expression of moral agency The relationship between place and moral agency in
      home care nursing is explored in this paper. The notion of place is argued to
      have relevance to moral agency beyond moral context. This argument is
      theoretically located in feminist ethics and human geography and is supported
      through an examination of historical documents (1900-33) that describe the
      experiences and insights of American home care/private duty nurses or that are
      related to nursing ethics. Specifically, the role of place in inhibiting and
      enhancing care, justice, good relationships, and power in the practice of private
      duty nurses is explored. Several implications for current nursing ethics come out
      of this analysis. (i) The moral agency of nurses is highly nuanced. It is not
      only structured by nurses' relationships to patients and health professionals,
      i.e. moral context, it is also structured by the place of nursing care. (ii)
      Place has the potential to limit and enhance the power of nurses. (iii) Some
      aspects of nursing's conception of the good, such as what constitutes a good
      nurse-patient relationship, are historically and geographically relative.

PMID- 12071909
TI  - Police and pastoral power: governmentality and correctional forensic psychiatric
      nursing.
AB  - Police and pastoral power: governmentality and correctional forensic psychiatric
      nursing Since 1978, the federal inmates of Canada have had access to a full range
      of psychiatric care within the penitentiary system. Several psychiatric units are
      now integrated into the correctional services of Canada. This paper presents the
      results of a grounded theory doctoral study undertaken in a multilevel secured
      psychiatric ward within the Canadian federal penitentiary system. The author
      describes and discusses the results of qualitative data that emerged from his
      fieldwork. The concept of governmentality, as defined by the late French
      philosopher Michel Foucault, constitutes one of the major theoretical tools that
      were helpful in analyzing these data. Police and pastoral power, two dimensions
      of the security apparatus of governmentality, were found to be useful in
      understanding and characterizing nursing practice caught between the penal and
      the psychiatric dispositifs. A Foucauldian perspective allows one to understand
      the manner in which forensic psychiatric nursing is involved in the governance of
      mentally ill inmates through three forms of power - sovereign, disciplinary and
      pastoral - which have posited nursing practice as a strategic tool of the
      correctional services. This research consists of a study of nursing practice in
      an extreme setting that deserves a radical analysis.

PMID- 12071908
TI  - Academics and practitioners: nurses as intellectuals.
AB  - Academics and practitioners: nurses as intellectuals In the author's experience,
      nurse educators working in universities generally accept that they are
      'academics', but dismiss suggestions that they are 'intellectuals' because they
      see it as a pretentious description referring to a small number of academics and
      aesthetes who inhabit a conceptual world beyond the imaginative capacity of most
      other people. This paper suggests that the concept of the 'intellectual', if not
      the word itself, be admitted into nursing discourse through the adoption of a non
      elitist Gramscian understanding, similar to the more recently formulated
      conception of the reflective practitioner. According to the Italian Marxist
      scholar Antonio Gramsci, intellectuals are those people who develop ways in which
      to construct the conditions of their own existence, a possibility he believed was
      open to all. It is suggested that, from a Gramscian perspective, all nurses are
      intellectuals to varying degrees, and nurse educators should not only be
      nurturing their own intellectualism but also the potential for intellectualism as
      it exists within each individual. The ways in which this project are related to
      Habermasian critical theory are also briefly outlined.

PMID- 12071910
TI  - Understanding between care providers and patients with stroke and aphasia: a
      phenomenological hermeneutic inquiry.
AB  - Understanding between care providers and patients with stroke and aphasia: a
      phenomenological hermeneutic inquiry The present study illuminates the
      understanding in communication between formal care providers and patients with
      stroke and aphasia. Five care providers and three such patients participated in
      the study. Video recordings were made during conversations about pictures (n =
      15), and the care providers were also interviewed (n = 15) after the video
      recorded conversations. A phenomenological hermeneutic method of interpretation
      of the interview text was used. The findings showed that a range of conditions
      for 'understanding and being understood' in the communication on the part of the
      care providers exists. These different conditions are: lacking both knowledge and
      understanding; having knowledge but not necessarily accompanied by understanding;
      and being in understanding. Within the condition 'being in understanding', the
      care providers create a feeling of at-homeness in a relaxed atmosphere and thus
      have the opportunity to be in 'understanding and being understood' together with
      the patient. The condition 'being in understanding' appears in connection with
      the care providers' creating of a 'calm liturgy of caring' by mediating humility
      and calm vitality affects to the patients, and further, when needed, being
      present on the level of mystery, i.e. caring communion.

PMID- 12071911
TI  - Nursing on paper: therapeutic letters in nursing practice.
AB  - Nursing on paper: therapeutic letters in nursing practice This paper offers a
      selected piece of interpretive research extracted from the context of a larger
      research study. The hermeneutic research inquiry described in this paper involved
      the examination of the nursing and family therapy intervention of therapeutic
      letters. It incorporated the textual interpretation of 11 therapeutic letters,
      clinical sessions with three families, clinical team discussions, and research
      interviews with four family members and three nurse clinicians who participated
      in the writing of the letters. This particular paper extracts segments of the
      research related to the letters received by two participants, as well as some
      general findings, with a focus on the possibilities and influences of therapeutic
      letters in nursing practice. The findings of this research offer suggestions, not
      as a template, but as an inspiration and evocation to write therapeutic letters
      that address the obligation of meeting people experiencing illness at the point
      of their suffering, with words and questions that invite relationship,
      reflection, and are large enough to sustain a meeting.

PMID- 12071912
TI  - Hermeneutics and narration: a way to deal with qualitative data.
AB  - Hermeneutics and narration: a way to deal with qualitative data This article
      focuses a hermeneutic approach on the interpretation of narratives. It is based
      on the French philosopher Paul Ricoeur's theory of interpretation but modified
      and used within a caring science paradigm. The article begins with a presentation
      of the theoretical underpinnings of hermeneutic philosophy and narration, as well
      as Ricoeur's theory of interpretation, before going on to describe the
      interpretation process as modified by the authors. The interpretation process,
      which consists of several stages, is exemplified and discussed using a single
      case from a larger study on suffering. The results of that study indicate that
      the struggle of suffering is perceived as a struggle formed between shame and
      dignity, and that nurses must engage in the process of preserving and restoring
      the dignity of their suffering patients. The authors suggest that Ricoeur's
      theory of interpretation is useful when trying to understand narrative data if
      the researcher realises that the process of distanciation, although central in
      Ricoeur's thinking, is not the goal of the process but rather a means to deal
      with the researcher's pre-understandings. According to Ricoeur, distanciation is
      accomplished by putting the context aside and dealing with the text 'as text' and
      thereby explaining its meaning. Explanation thus becomes the dialectic
      counterpart to understanding in the interpretation process. The researchers
      further argue that distanciation must be followed by reflection, where the
      interpretations are linked back to the empirical context.

PMID- 12071913
TI  - Reflexivity and detachment: a discursive approach to women's depression.
AB  - Reflexivity and detachment: a discursive approach to women's depression This
      paper explores a discursive approach to understanding women's depression by
      presenting the results of research into women's narratives of their experiences.
      The discursive approach taken acknowledges women's immersion in cultural
      practices that determine the subject positions available to them and places a
      value on attributes of reflexivity and detachment that are not usually associated
      with their performance. The social and cultural context of the individual's
      experience is significant because if the focus is simply on the individual this
      supposes that the problem lies solely with the individual. An understanding of
      cultural expectations and their relation to mental distress is important to
      mental health nursing practice. The psychotherapeutic relationship that is
      fundamental to mental health nursing practice requires an understanding of the
      meaning of individual's responses in their cultural context in order to provide
      facilitative and meaningful care for the women that they nurse.

PMID- 12071914
TI  - Purists, eclectics, muddlers and movers: a caution on categorising.

PMID- 12071915
TI  - Oral perception and oral motor ability in edentulous patients with stroke and
      Parkinson's disease.
AB  - Oral perception and oral motor ability were assessed in edentulous patients with
      stroke, Parkinson's disease, and an age and gender matched control group.
      Standard stereognosis and oral motor ability tests were performed, with and
      without complete dentures in situ. Statistical comparisons were made using ANOVA,
      Levene's test and paired t-tests. Stroke patients had significantly poorer
      stereognostic measures than Parkinson's disease patients and controls (P < 0.02).
      Stereognostic measures were better in all groups when dentures were worn. There
      were no differences in oral motor ability between groups. Oral stereognosis was
      significantly impaired in stroke patients. Oral stereognostic ability was better
      in all groups when dentures were worn. The oral motor ability test lacked the
      sensitivity to detect differences in motor ability between experimental groups.
      Edentulous patients with stroke should be encouraged to wear dentures during the
      rehabilitation phase as oral stereognosis is then less impaired.

PMID- 12071916
TI  - Variation in masticatory muscle activity during subsequent, submaximal clenching
      efforts.
AB  - In previous studies to the relative contribution of the jaw closing muscles to
      the maintenance of submaximal clenching levels, a considerable variation in the
      electromyography (EMG) activities of these muscles during subsequent efforts was
      found. In this study, it was examined to what extent this variation could be
      explained by coincidental variations in mandibular positioning. From seven
      healthy individuals, a total of 90 EMG sweeps was recorded: three conditions
      (intercuspal position and two types of stabilization appliances) x three
      clenching levels (10, 30 and 50% of maximum voluntary contraction level) x 10
      repetitions. Mandibular position was monitored with a six degrees of freedom opto
      electronic jaw movement recording system. Variations in mandibular positioning
      during subsequent, submaximal clenching efforts explained up to 25% of the
      variance in the indices that quantify the relative contribution of the jaw
      closing muscles to the total clenching effort (P=0.000; ANOVA). Only a weak
      dependency of positioning upon clenching condition was found whereas during
      higher clenching levels, the positioning effect tended to be smaller than during
      lower levels. In conclusion small, coincidental variations in mandibular
      positioning during subsequent clenching efforts partly explain the variance in
      EMG activity of jaw closing muscles, especially at lower clenching levels.

PMID- 12071917
TI  - Raman scattering determination of the depth of cure of light-activated
      composites: influence of different clinically relevant parameters.
AB  - The purpose of this research was to determine the depth of cure of light
      activated composites in relation with different clinically relevant parameters. A
      Raman spectroscopic method has been used. The measurement of cure is made on a
      relative basis by comparing the vibration band of the residual unpolymerized
      methacrylate C=C bond at 1640 cm-1 against the aromatic C=C stretching band at
      1610 cm-1 used as an internal standard. The information gained draw attention to
      the importance of light transmission during the exposure. The influence of
      sample's thickness on the depth of cure is illustrated by a second order
      polynomial regression. The shade and translucency of the resin composite also
      modify the light transmission and thus have a significant influence on the degree
      of conversion. Moreover the light-source intensity and the distance from the
      curing tip are important parameters of influence. A significant reduction of the
      depth of cure is observed for all sample thickness of resin composite tested when
      using a light device with an intensity of 300 mW cm-2 as well as using a distance
      from the curing tip higher than 20 mm.

PMID- 12071918
TI  - Magnetic resonance imaging findings of internal derangement in temporomandibular
      joints without a clinical diagnosis of temporomandibular disorder.
AB  - The purpose of this study was to assess the prevalences of magnetic resonance
      (MR) imaging findings of internal derangement (ID) in temporomandibular joints
      (TMJs) without a specific clinical diagnosis of temporomandibular disorder (TMD),
      and to investigate whether in this TMJ group the variable of pain may be linked
      to MR imaging findings of ID. The study comprised 109 patients, who were assigned
      a clinical uni- or bilateral TMJ-related diagnosis of 'absence of TMD'. Bilateral
      sagittal and coronal MR images were obtained subsequently to establish the
      prevalence of TMJ ID. An MR imaging diagnosis of ID was found in 99 (55.9%) of
      the 177 TMJs investigated. About 30.3% of the closed mouth-related TMJ positions
      characterized by disc displacement presented with anterior disc displacement,
      while 27.3% had anterolateral and 25.3% anteromedial disc displacement. Analysis
      of the data revealed the presence of TMJ pain to be associated with significantly
      more MR imaging diagnoses of disc displacement without reduction than disc
      displacement with reduction (P < 0.05), while there was no significant difference
      in the prevalences of ID and those of absence of ID (P > 0.05). Using chi-square
      analysis, no significant relationship was found between the presence of TMJ pain
      and the MR imaging diagnosis of TMJ ID (P=0.93). Use of the kappa statistical
      test indicated poor diagnostic agreement between the presence of TMJ pain and the
      MR imaging diagnosis of ID (kappa=0.01). The results suggest TMJs with a clinical
      diagnosis of 'absence of TMD' to be associated with a high rate of IDs, while in
      these instances the clinical variable of TMJ pain may have no effect on
      prevalences of MR imaging diagnoses TMJ ID. The data confirm the aspect of
      clinical diagnostic criteria as an unreliable instrument in predicting MR imaging
      diagnoses of TMJ ID.

PMID- 12071919
TI  - Inhibition of artificial secondary caries by fluoride-releasing adhesives on root
      dentin.
AB  - Fluoride-releasing materials can be expected to inhibit the secondary caries. The
      aim;of this study was to evaluate the effect of fluoride-releasing adhesives on
      inhibition of secondary caries in outer and wall lesions. Two commercial fluoride
      releasing adhesives, Reactmer bond (RB) and One-up bond F (OB), and a commercial
      adhesive without fluoride release, Mac-bond II (MB), were used prior to placement
      of restorative materials without fluoride release, Lite-fil II A (LF) and
      Estelite (EL), and a fluoride-releasing restorative material, Reactmer paste
      (RP). Class V cavities prepared on extracted human premolars were restored with
      various combinations of the materials: MB/EL, OB/EL, RB/LF and RB/RP. The
      restored teeth were incubated in bacterial medium containing sucrose with
      Streptoccus mutans for 14 days. Microradiographs of specimens showed no wall
      lesions in all groups and an acid-resistant layer adjacent to the restoration in
      the caries-like lesion. OB/EL, RB/LF and RB/RP groups showed thicker layers than
      the MB/EL group. The RB/RP group formed the shallowest outer lesion among all
      groups. These results indicate that fluoride-releasing adhesives are effective in
      the prevention of wall lesions but exhibit little outer lesion inhibition.
      Therefore, combined restoration using a fluoride-releasing adhesive and fluoride
      releasing restorative material should be selected to inhibit secondary caries.

PMID- 12071920
TI  - Enamel tensile bond strength and morphology of resin-enamel interface created by
      acid etching system with or without moisture and self-etching priming system.
AB  - The purpose of this study was to estimate the effect of three types of different
      adhesive systems on enamel adhesion. Scotchbond Multi-Purpose (MP) as a
      traditional system, Single Bond (SB) as a wet-bonding system and Clearfil SE Bond
      (SE) and Unifil Bond (UB) as self-etching priming systems were used. Bovine
      enamel was treated with each system and tensile bond strength (TBS) of resin to
      the enamel was measured. The conditioned enamel surfaces and resin-enamel
      interfaces were also morphologically observed with scanning electron microscope
      (SEM). The mean TBS for MP, SB, SE and UB were 15.3, 13.7, 14.3 and 11.6 MPa,
      respectively. There was no significant difference in mean TBS among all products
      but the traditional system showed the most stable TBS. In SEM observations, self
      etching primer created a weaker etched pattern on the enamel surface than
      phosphoric acid. At the resin-enamel interfaces, thick tag-like extensions
      penetrated into the enamel etched with phosphoric acid regardless of using the
      wet-bonding technique, while self-etching primer created thin lamina-like resin
      penetrations. These results indicate that the traditional system with phosphoric
      acid etching exhibits the most stable enamel adhesion although the enamel-bonding
      promoting abilities of these adhesive systems are equivalent to each other.

PMID- 12071921
TI  - Local kinematic and anthropometric factors related to the maximum mouth opening
      in healthy individuals.
AB  - The aim of the present study was to investigate the influence of local
      anthropometric (mandibular length and width) and kinematic (forward and downward
      condylar translation and angle of rotation) variables upon the maximum mouth
      opening (MMO). Thirty-five healthy individuals, 17 men and 18 women, mean age 23
      years with a range from 18 to 31 years, performed six to eight maximal,
      symmetrical and pain-free open-close movements during a 20-s recording.
      Mandibular movements were recorded by means of the OKAS-3D jaw movement recording
      system. A stepwise regression analysis showed that differences in MMO are mainly
      explained by differences in the angle of rotation and in mandibular length
      (R2adj=91.5%). Including the downward and forward component of condylar
      translation into the regression model increased the explained variance with only
      4.7%. A second stepwise analysis showed that the angle of rotation is positively
      related to the forward component of the condylar translation and negatively
      related to its downward component (R2adj=52.7%). In conclusion, differences in
      MMO between healthy individuals are, to a large extent, explained by differences
      in the angle of rotation and in mandibular length. In its turn, differences in
      the angle of rotation are related to differences in condylar translation.

PMID- 12071922
TI  - Evaluation of the accuracy and reproducibility of a replication technique for the
      manufacture of electroconductive replicas for use in quantitative clinical dental
      wear studies.
AB  - This work sought to evaluate the accuracy and reproducibility of a replication
      process that formed electroconductive replicas from addition cured silicone
      impressions for the purposes of monitoring tooth surface loss. Replicas were
      constructed by painting the surface of impressions with one of three high silver
      content electroconductive paints [Electrocure (EC), RS Silver Paint (SP) and
      Electrolube (EB)] and, once dry, backing this up with a cyanoacrylate based gel
      material (Zapit) and die stone. For each paint an impression was recorded of a
      gauge block of known step height (1270 microm) and five impressions of the
      palatal surface of a laboratory standard maxillary central incisor were also
      recorded. All impressions were taken using an addition cured silicone impression
      material (President). The resultant electroconductive replicas were mapped using
      a computer controlled probe. This data was analysed to determine both the
      replica's step height and, using surface matching techniques, the reproducibility
      of the replication process. The mean step heights recorded were; EC=1268.43
      (s.d.=12.09), SP=1267.09 (s.d. 1.77) and EB 1299.58 (s.d. 14.47). Both EC and SP
      recorded the step height to within 3 microm. In the repeat replication of the
      palatal surface of an upper central incisor SP maintained a greater constancy of
      surface topography (99.6%) that was statistically superior to both EC (P < 0.05)
      and EB (P < 0.01). The SP was therefore the preferred paint for this technique.
      Bearing this in mind the replication technique was both accurate and reproducible
      but vigilance, as to the selection of paint for the process, should be exercised
      so as not to affect the good accuracy and reproducibility of the technique.

PMID- 12071923
TI  - The effect of thermocycling on five adhesive luting cements.
AB  - The importance of bond strengths between dental luting cements and dental
      restorative materials has become increasingly important as a result of the
      adhesive technologies that have been developed over recent years. This study
      investigated the effect on tensile bond strength at the metal to cement interface
      for a semiprecious alloy for different prepared surfaces, cements and ageing
      regimes. At 24 h following preparation, silicoating and C & B Metabond appear to
      have distinct advantages in terms of interfacial bond strength, which was also
      noted after storage for 7 days in buffered saline. After thermocycling only
      silicoating conferred greater interfacial tensile strength, and any advantage
      that the 4-Methacryloxyethyltrimellitic anhydride (4-META) chemistry may have had
      at 24 h was no longer apparent. The poorest performing cement regardless of the
      ageing regime was Aquacem, although in relative terms its performance improved
      after 24 h. This preliminary investigation indicated that in vitro environmental
      ageing including thermocycling erodes the claimed advantages of some more novel
      dental adhesives. This may have important clinical consequences in their usage,
      although it must be appreciated that current thermocycling methodology may not be
      an accurate predictor of in vivo performance.

PMID- 12071924
TI  - Antibacterial and physical properties of resin modified glass-ionomers combined
      with chlorhexidine.
AB  - The purpose of this study was to determine the effect on mechanical properties
      and antimicrobial activity of the addition of chlorhexidine (CHX) to a resin
      modified glass-ionomer (Photac-fil, ESPE, Norristown, PA, USA). Chlorhexidine
      diacetate was combined with a resin modified glass-ionomer material at a
      concentration of 5%. The samples were tested for hardness, tensile strength and
      erosion at 24 h and 6-week intervals and for elution of CHX and antimicrobial
      activity weekly for 6 weeks. At 24 h there was no significant difference in
      hardness between the two groups, but at 6 weeks the resin modified glass-ionomer
      group was significantly harder than the CHX groups (P < 0.05). The diametral
      tensile strength test indicated no difference between the control and CHX groups
      at 24 h or at 6 weeks. The jet erosion test demonstrated significantly less
      erosion with the CHX group at 24 h but at 6 weeks the CHX group showed
      significantly more erosion than the control group. The chemical assay data
      demonstrated a peak elution of CHX at week 1 with residual amounts at weeks 2 and
      3. The microbial data demonstrated that the CHX group had a significant reduction
      in Streptococcus mutans numbers for weeks 1-3, but after week 4 there was no
      difference between the glass-ionomer with and without CHX. The addition of CHX to
      resin modified glass-ionomer altered hardness and erosion of the resin-modified
      glass-ionomer, but because there are no material specifications, it is difficult
      to determine clinical implications. Chlorhexidine did significantly improve the
      antimicrobial effect of the glass-ionomer which was consistent with the chemical
      assay data. The results indicated that the addition of CHX to resin modified
      glass-ionomer material (Photac-fil) did not seriously degrade the physical
      properties during the time period tested and that the addition of CHX resulted in
      a greater reduction in S. mutans when compared with glass-ionomer alone.

PMID- 12071925
TI  - Shear bond strengths of saliva contaminated 'one-bottle' adhesives.
AB  - The aim of this study was to investigate the effect of saliva contamination on
      the bond strengths of three one-bottle bonding systems. The dentin of 90 recently
      extracted, non-carious human molar teeth was exposed and ground wet on 500 grit
      silicon carbide (SIC) paper to establish a bonding surface in superficial dentin.
      Specimens were randomly assigned to nine groups of 10 teeth each. Three testing
      conditions are: (i) contamination with fresh saliva (pH 5.5) after acid etching,
      (ii) contamination with fresh saliva after bonding application, and (iii) no
      contamination. Three adhesive systems are: syntac single component, prime & bond
      NT, and gluma one bond. Cylinders of composite were applied via PTFE
      (polytetrafluroethylene) split mould and light cured to the dentin surfaces. All
      specimens were thermocycled (5000 cycles) between baths of 5 and 55 degrees C.
      Shear bond strengths were measured using an Instron Universal testing machine at
      a crosshead speed of 1 mm min-1. Two-way ANOVA was used to analyse the data. The
      results of this study indicated that the saliva contamination of dentin has no
      adverse effect on the bonding efficiency of one-bottle adhesive systems (P >
      0.05). No statistically significant differences were found between the shear bond
      strengths of tested adhesives.

PMID- 12071927
TI  - Differences in the fatigue of masticatory and neck muscles between male and
      female.
AB  - The purpose of this study was to investigate the nature of fatigue and recovery
      of masticatory and neck muscles and the differences between sexes in normal
      subjects during experimentally induced loading. Subjects consisted of eight males
      (mean age: 27.6 years) and eight females (mean age: 24.2 years) selected from the
      volunteers in the Faculty of Dentistry, Hiroshima University. The inclusion
      criteria for the subjects were as follows: (1) good general health, (2) normal
      horizontal and vertical skeletal relationships, (3) no severe malocclusions and
      (4) no complaints of temporomandibular disorders. Each subject was requested to
      bite an occlusal-force meter with 98, 196 and 294 N forces on the first molar
      region per side for 45 s. Activities of the masseter and sternocleidomastoid
      (SCM) muscles were recorded during these performances. Fatigue and recovery
      ratios were calculated with mean power frequency of power spectrum using a fast
      Fourier transform algorithm. Significant differences in the fatigue ratios
      between both sexes were found for the masseter muscle with 98, 196 and 294 N bite
      forces. Meanwhile, the SCM presented a significant difference between both sexes
      only at 98 N biting. Significant differences in the recovery ratios between both
      sexes were more prominent in the masseter muscle than in the SCM. These results
      suggest that the differences in muscle endurance between sexes may have some
      association with higher susceptibility of craniomandibular disorders in females
      than in males.

PMID- 12071926
TI  - Evaluation of design parameters of osseointegrated dental implants using finite
      element analysis.
AB  - Finite element analyses were performed for various shapes of dental implant to
      study effects on stress distribution generated in the surrounding jaw bone and to
      determine an optimal thread shape for even stress distribution. It was found that
      the square thread shape filleted with a small radius was more effective on stress
      distribution than other dental implants used in the analyses. Additional analyses
      were performed on the implant with the thread shape obtained from previous
      analyses for varying other design parameters, such as the width of thread end and
      height of thread for various load directions, to determine the optimal dimensions
      of the implant. Stress distribution was more effective in the case when the width
      of thread end and the height of thread were 0.5p and 0.46p, respectively, where p
      is the screw pitch. Then, using the optimal implant thread dimensions determined
      previously, stress analyses were performed with various screw pitches and implant
      lengths, to investigate effects on stress distribution and to find the way to
      reduce the maximum effective stress generated in the jaw bone. Results show that
      the maximum effective stress decreased not only as screw pitch decreased
      gradually but also as implant length increased.

PMID- 12071928
TI  - The effect of thermocycling on peel strength of six soft lining materials.
AB  - The bond strength of two heat-cured and four cold-cured soft lining materials was
      compared using a peeling test method before and after thermocycling. Tested soft
      lining materials were Molloplast B, Mollosil, Ufigel P, Ufigel C, Permaquick and
      Permaflex. Six specimens, 6.5 x 2 x 0.3 cm, for each group were prepared
      according to the manufacturers' instructions. Control groups were stored in a
      humidor for 24 h, whereas the others were thermocycled in a water bath between
      the 5 and 55 degrees C for 5000 cycles. Peel strength of samples were measured
      using an Instron Universal testing machine at a cross-head speed of 5 mm min-1.
      The types of failure were observed using an electron microscope. The highest peel
      bond strength values were calculated for Permaflex and Permaquick before and
      after thermocycling, respectively. Molloplast B, Mollosil, Ufigel P and
      Permaquick demonstrated an increase in peel strength after thermocycling, with
      Permaquick lining material having statistically significant increase. However,
      decrease in peel strength was observed for Ufigel C and Permaflex after
      thermocycling. Failure mode within the control groups was cohesive for Molloplast
      B, Permaquick and Permaflex, whereas adhesive for Ufigel P and Ufigel C. Mollosil
      demonstrated a mixed mode of failure for both thermocycled and control groups.

PMID- 12071929
TI  - Association of horizontal and vertical overlap with prevalence of
      temporomandibular disorders.
AB  - The aim of the study was to evaluate the relationship between horizontal (HO) and
      vertical overlap (VO) and prevalence of temporomandibular disorders (TMD) in a
      non-patient population. Out of the total number of subjects (230), 65.7% subjects
      were classified as asymptomatic, 5.7% subjects had muscle disorders (MD)
      (myalgia), 9.1% subjects had disc displacement with reduction (DDR), while 19.6%
      subjects had disc displacement with reduction associated with muscle disorder
      (DDR + MD) (myalgia). The HO equal to or greater than 5 mm was significantly more
      prevalent in the symptomatic patients (MD, DDR, DDR + MD) than in the
      asymptomatic group (P < 0.001). The VO equal to or > 5 mm also demonstrated
      statistically significant difference (P < 0.006) between the symptomatic
      (suffering from DDR, and DDR + MD) and asymptomatic subjects. Conclusion of the
      study is that the HO and VO equal to or > 5 mm was more present in the group of
      subjects with diagnosis of a TMD (DDR and MD), what distinguishes this group from
      the group of asymptomatic subjects.

PMID- 12071930
TI  - Histopathological changes in the tissues under a denture base in experimental
      osteoporosis with a non-pressure covering or bearing continuous pressure.
AB  - In this study, the experimental denture base on the hard palate of the molar
      region of osteoporotic rats was designed to cover without any mechanical pressure
      or to load continuous pressure (0.5, 1.5 or 3.4 kPa). Experimental osteoporosis
      was induced by ovariectomy and feeding on a low calcium diet. Histopathological
      changes induced by non-pressure covering or continuous pressure in the tissues
      under the experimental denture bases were examined. Regarding the histological
      changes induced by continuous pressure, this was evaluated in relation to the
      time course of the intensity of the continuous pressure. In the tissues under the
      denture base in osteoporotic condition with non-pressure covering, no
      histopathological changes caused by non-pressure covering were observed except
      for a transient slight proliferative reaction in the epithelial ridge. The
      following histopathological changes were observed in the tissues under the
      denture base in the osteoporotic condition bearing continuous pressure; (i) bone
      resorption was induced on the periosteal surface (Ps) in the osteoporotic-3.4 kPa
      group, and on the pressure side of the endocortical surface (p-Ec) in the
      osteoporotic-1.5 and -3.4 kPa group, (ii) the appearance of osteoclasts on the p
      Ec in the osteoporotic-3.4 kPa group was earlier than that on the Ps in a same
      group, (iii) bone resorption on the pressure side of the Ec in the osteoporotic
      3.4 kPa group manifested at the earlier stage than that in the osteoporotic-1.5
      kPa group, (iv) bone formation following bone resorption on the p-Ec was observed
      more markedly than that on the Ps and (v) histopathological changes in the
      tissues under the denture base in experimental osteoporosis bearing continuous
      pressure had an intimate relationship with the initial intensity and the time
      course of continuous pressure.

PMID- 12071931
TI  - Dental anxiety and regularity of dental attendance in younger adults.
AB  - Dental anxiety constitutes a major problem for patients and dental care providers
      alike. The aim of this study was to examine the relationship between dental
      anxiety and regularity of dental attendance among young adults. A random sample
      of 15 course directors (1:50) was asked to participate in the study. Of these,
      only 10 course-directors agreed to handout the 500 questionnaires. All
      undergraduate students who participated in this study were asked to complete a
      questionnaire modified from Dental Fear Survey (DFS) questionnaire and 368
      (73.6%) filled forms were returned for statistical analysis. The results showed
      that only 20.9% were regular dental attendee while the majority (79.1%) were
      irregular attendee. The reasons given for irregular attendance were 'lack of
      time' (36%), 'treatment not needed' (34.1%), 'fear from dentist' (13.3%) and
      'cost' (16.6%). The sight and sensation of the injection and sight, sound, and
      sensation of the drill were the most common fear-eliciting stimuli. Increased
      heart rate was the commonest reported physiological response. Females had higher
      mean ratings, therefore tended to be more anxious than males. Dental anxiety
      represented by the mean responses to the items, was found to be higher in
      irregular dental attendee than regular attendee. In conclusion, this suggests
      that dental anxiety may affect the seeking of dental care, therefore to be taken
      into account when training dental care providers.

PMID- 12071933
TI  - Patients with idiopathic myelofibrosis show increased CD34+ cell concentrations
      in peripheral blood compared to patients with polycythaemia vera and essential
      thrombocythaemia.
AB  - The aim of the present work was to compare the results for some haematological
      variables in 12 patients with idiopathic myelofibrosis (IMF) with those of 21
      patients with polycythaemia vera (PV), 22 patients with essential
      thrombocythaemia (ET) and 10 healthy control subjects. In each patient and
      control subject peripheral blood was used for analysis of flow cytometric
      measurement of CD34-positive (CD34+) cells, in vitro colony growth and plasma
      erythropoietin (EPO) concentration. The mean concentration of CD34+ cells in the
      IMF group was 568 +/- 686 x 10(3) mL, which significantly (P<0.001 for each
      group) exceeded the means in PV, ET and control groups ((10.2 +/- 32.0) x 10(3)
      mL, 3.0 +/- 3.7 x 10(3) mL and 1.9 +/- 0.8 x 10(3) mL, respectively). The mean
      number of EPO-independent erythroid colonies (EEC) was 110 +/- 215 colonies per
      10(5) cells for the IMF patients. In comparison with the means for PV and ET
      patients (40 +/- 140 and 12 +/- 27 colonies per 10(5) cells, respectively) the
      difference did not reach statistical significance. The mean EEC for IMF patients
      was, however, significantly higher compared with the mean for the control
      subjects (P<0.05). The means for total erythroid colony growth with EPO added to
      the growth medium as well as for granulocyte-macrophage colony-forming units were
      significantly higher in the IMF group compared with the means for PV, ET and
      control groups (P<0.001 for each group). The mean plasma EPO was 204 +/- 290 IU/L
      in the patients with IMF compared with 6.6 +/- 7.9 IU/L in PV patients, 19.1 +/-
      23.2 IU/L in ET and 10.3 +/- 7.8 IU/L in the control subjects. Due to
      considerable differences in haemoglobin concentrations no relevant conclusions
      could be drawn from the results for plasma EPO concentrations. Indeed, the
      majority of patients with IMF, PV and ET were on myelosuppressive treatment;
      additionally most PV patients received phlebotomy therapy. The results of the
      present study suggest that the circulating pool of stem cells and progenitor
      cells in peripheral blood is significantly increased in IMF patients compared
      with PV and ET patients as well as healthy control subjects. The most likely
      source for the elevated CD34+ cell concentration in peripheral blood is
      progenitor cells of extra-medullar origin.

PMID- 12071934
TI  - Localisation and distribution of hyaluronan in normal bone marrow matrix: a novel
      method to evaluate impending fibrosis?
AB  - Bone marrow trephine biopsies from 30 healthy volunteers, 10 men and 20 women
      aged 18-60 yr were obtained for identification and localisation of hyaluronan
      (HYA). Fixation, decalcification and embedding were performed by two different
      methods, with identical results in both. For comparison bone marrow trephine
      biopsies from three patients with different haematological diseases and known
      fibrosis were studied. All bone marrow specimens were also stained for reticulin
      grading. HYA was found in the bone marrow specimens from healthy individuals in a
      pattern that was concordant with the reticulin staining, the common way of
      visualising bone marrow fibrosis. In bone marrow from the patients with known
      fibrosis the HYA and reticulin staining were both more intense and abundant.
      Interestingly, HYA was also found intracellularly in eosinophilic cells in normal
      bone marrow. HYA is a polysaccharide unique both in structural and biological
      properties, and in excess it may predict bone marrow fibrosis.

PMID- 12071935
TI  - De novo acute myeloid leukemia with multilineage dysplasia: treatment results and
      prognostic evaluation from a series of 44 patients treated with fludarabine,
      cytarabine and G-CSF (FLAG).
AB  - OBJECTIVES: To evaluate therapeutic results and prognostic factors from a series
      of 44 patients affected by de novo acute myeloid leukemia with multilineage
      dysplasia (MD-AML), treated with the combination of fludarabine, cytarabine and G
      CSF (FLAG). METHODS: Forty-four patients with de novo MD-AML were treated with
      the FLAG regimen. The median age was 61 yr (range 31-75 yr). Induction therapy
      consisted of the FLAG regimen; consolidation included idarubicin plus cytarabine.
      Patients with a compatible donor and aged less than 55 yr were programmed to
      receive allogeneic bone marrow transplantation (BMT), while in those without a
      donor and aged less than 65 yr autologous transplantation with peripheral blood
      stem cells mobilized by a consolidation regimen plus G-CSF was planned. Bone
      marrow harvest was performed in poor mobilizers. RESULTS: Complete remission (CR)
      was achieved in 28 out of 44 patients (64%). Death in induction occurred in four
      patients (9%), while 12 patients (27%) were resistant to FLAG. Toxicity of
      consolidation was negligible. Most patients aged less than 60 yr and achieving CR
      were eligible for transplantation procedures, the main reason of exclusion being
      early relapse. Median overall survival and disease free survival were 16 and 22
      months, respectively. Unfavorable cytogenetics was the only parameter
      significantly related to inferior clinical outcome following multivariate
      analysis. CONCLUSION: Multilineage dysplasia per se is not an adverse prognostic
      factor in AML patients treated with the FLAG regimen. Favorable results are
      obtained in patients with intermediate karyotype, while in those with adverse
      cytogenetics new approaches are clearly needed. The toxicity of the regimen is
      also acceptable in the elderly, and following induction/consolidation, most
      patients may be submitted to transplantation procedures.

PMID- 12071936
TI  - Favourable response to antithymocyte or antilymphocyte globulin in low-risk
      myelodysplastic syndrome patients with a 'non-clonal' pattern of X-chromosome
      inactivation in bone marrow cells.
AB  - OBJECTIVE: Antithymocyte and antilymphocyte globulin (ATG/ALG) have a therapeutic
      effect in about 30% of patients with myelodysplastic syndromes (MDS). We were
      interested to know whether responding patients achieve clonal or polyclonal
      remissions. PATIENTS: Ten women with low-risk MDS received either ALG or ATG.
      Before treatment and 3, 6, and 12 months later, X-chromosome inactivation
      patterns of peripheral blood T lymphocytes were compared with those of peripheral
      blood granulocytes or bone marrow cells, using the human androgen receptor gene
      assay and the phosphoglycerate kinase-1 assay. RESULTS: Six women did not respond
      to therapy. Prior to treatment, four of them had a monoclonal, one had an
      oligoclonal, and one had a skewed X-chromosome inactivation pattern (XCIP). Four
      patients responded to ATG/ALG. Three of them were informative in our X
      inactivation assays, and showed a non-clonal XCIP which did not change
      significantly after treatment with ATG/ALG. CONCLUSION: A non-clonal XCIP in the
      bone marrow was associated with a response to ATG/ALG. Non-clonal XCIPs do not
      necessarily imply that there is no pathological clone. By definition, they just
      indicate that there is no evidence of a clone contributing more than 50% of cells
      in a sample. Non-clonal XCIPs may therefore be attributable to incomplete clonal
      expansion. This, in turn, might be explained by a vigorous immune attack against
      the MDS clone, which simultaneously causes collateral damage in the remaining
      normal haemopoiesis. In such patients, ATG/ALG may improve normal haemopoiesis by
      relieving the immunological pressure on the innocent bystanders.

PMID- 12071937
TI  - Somatic hypermutation and V(H) gene usage in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is considered to derive from naive, pregerminal center
      (GC) CD5+ B-cells. However, the cell of origin has been questioned in recent
      studies that showed somatic hypermutations in the immunoglobulin (Ig) variable
      heavy chain (V(H)) genes in subsets of MCL. To clarify this issue, we analyzed
      the IgV(H) genes for the presence of somatic hypermutations in 51 MCL cases.
      Twenty percent of the MCL cases displayed somatically mutated V(H) genes (defined
      as >2% mutated), whereas 80% showed unmutated V(H) genes. This finding suggests
      that MCL is a genetically heterogeneous disease, with the majority of cases
      originating from unmutated pre-GC B-cells and a subset deriving from more mature
      B-cells which have been exposed to the GC environment and have undergone somatic
      hypermutation. A biased V(H) gene usage has been demonstrated in several B-cell
      malignancies; however, this has not yet been investigated in MCL, although V(H)4
      34 overusage has been indicated by small studies. Interestingly, we found a
      restricted usage of three individual V(H) genes in our MCL material; V(H)4-34
      (22%), V(H)3-21 (16%) and V(H)5-51 (12%). This novel finding of preferential V(H)
      gene usage in half of the MCL cases may suggest an antigen driven process
      occurring in B-cells expressing specific VH genes, thus implicating that Ig
      specificity could be involved in mantle cell lymphoma development.

PMID- 12071938
TI  - A population-based study of the outcome for patients with first relapse of
      Hodgkin's lymphoma.
AB  - BACKGROUND: Our aims were to evaluate the response to salvage treatment in
      relation to initial treatment and to evaluate prognostic factors at the time of
      relapse in an unselected population of relapsing patients with Hodgkin's lymphoma
      (HL). PATIENTS AND METHODS: In total, 124 patients younger than 60 yr of age with
      initial diagnosis of HL in Sweden relapsed between 1985 and 1995. RESULTS: Fifty
      eight patients relapsed after initial treatment with radiotherapy (RT) only, 62
      after combination chemotherapy (CT), of whom 30 had received additional involved
      field RT, and four after a short course of CT followed by extended-field RT. For
      37 patients among the 58 relapsers after initial RT treated according to the
      recommendations of the National guidelines, the 5-yr Hodgkin-specific survival
      (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which
      is not inferior to survival in patients with primarily advanced stages. It was
      poorer in the 21 patients who initially had received RT only, even though they
      had been recommended for more extensive treatment. For patients initially treated
      with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%.
      Bulky disease and age at diagnosis strongly affected survival in a multivariate
      analysis. CONCLUSIONS: Patients initially treated with RT who relapse have a
      favourable outcome, provided they have been treated according to the
      recommendations of the guidelines at the time of diagnosis. Initially bulky
      disease and, as a consequence, additional RT as part of the initial treatment
      negatively affect survival at relapse in patients initially treated with a full
      course of CT.

PMID- 12071939
TI  - Remission of transformed myelodysplastic syndrome with fibrosis after danazol
      therapy.
AB  - Danazol has been used with success in some hematological diseases, but there is
      no report of this treatment in acute leukemia. We report here a case of remission
      of myelodysplastic syndrome with myelofibrosis in transformation after danazol
      therapy in a 72-yr-old man. The role of danazol in remission induction is briefly
      discussed.

PMID- 12071940
TI  - Mononucleosis syndrome and acute monocytic leukemia.
AB  - The association of infectious mononucleosis and an immunocompromised host such as
      occurs in acute leukemia is reported. The most common cause of infectious
      mononucleosis is Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Patients
      with mononucleosis syndrome caused by other agents are rare. We report a case of
      acute monocytic leukemia (AMoL) who developed varicella zoster virus (VZV)
      mononucleosis syndrome in the bone marrow recovery phase after myelosuppression
      due to high-dose cytarabine. Mononuclear leukocytes appearing during the
      mononucleosis syndrome were very similar to the initial leukemic cells. Varicella
      zoster virus mononucleosis syndrome was confirmed by delayed herpes zoster rash
      with dermatomal distribution.

PMID- 12071941
TI  - Thrombocytopenic purpura and cardiomyopathy in pregnancy reversed by combined
      plasma exchange and infusion.
AB  - Thrombocytopenia and hemolytic anemia have been seen with thrombotic
      thrombocytopenic purpura (TTP), HELLP syndrome (hemolysis, elevated liver
      enzymes, and low platelets), and hemolytic uremic syndrome (HUS). Differentiating
      between TTP, HUS, and HELLP syndrome is often difficult. Coexistence of TTP and
      HELLP is possible. Cardiomyopathy occurring in pregnancy can be idiopathic or
      associated with TTP. We describe a previously healthy woman who developed
      thrombocytopenia and hemolysis at 34 wk gestation. The patient underwent delivery
      after transfusion with platelets and RBCs. The suspicion of TTP was raised, and
      plasma exchange was begun by the third hospital day. On the seventh day of
      treatment, the patient developed shortness of breath, and an echocardiogram
      showed global hypokinesis with an ejection fraction of 25%. Plasma infusion, one
      unit q 4 h, was initiated in addition to the daily plasma exchange. The patient
      improved and her ejection fraction normalized. Plasma exchange and infusion and
      corticosteroids were gradually tapered off. von Willebrand factor (vWF) protease
      activity in the plasma upon transfer was completely deficient with the presence
      of inhibitor. This case illustrates that vWF protease assay and detection of
      inhibitor can be used for the diagnosis of TTP during pregnancy; and a severe
      cardiomyopathy in TTP can be reversed rapidly with combined plasma exchange and
      infusion.

PMID- 12071942
TI  - Beneficial effects of rituximab on primary cold agglutinin disease refractory to
      conventional therapy.
AB  - A case is reported of lymphoplasmacytoid lymphoma (LPL) associated with a
      monoclonal immunoglobulin (Ig) M and cold agglutinin disease (CAD) that was
      successfully treated with rituximab. A 52-yr-old male was admitted with a direct
      antiglobulin test positive haemolytic anaemia and thrombocytopenia associated
      with monoclonal IgM. Bone marrow examinations disclosed the marked infiltration
      of medium-sized lymphoma cells with plasmacytoid differentiation that indicated
      non-Hodgkin's lymphoma of B-cell origin (LPL). Prednisolone and combination
      chemotherapy were temporarily effective for both anaemia and thrombocytopenia,
      although these strategies became refractory and bone marrow lymphoplasmacytosis
      persisted. CAD ameliorated, and the serum level of IgM decreased in association
      with the disappearance of lymphoma cells and clonal rearrangement of the Ig heavy
      chains in the bone marrow after treatment with rituximab. Rituximab played a
      significant role in the treatment of refractory CAD associated with LPL.

PMID- 12071943
TI  - A novel case of haemoglobin H disease associated with clinical and morphological
      characteristics of congenital dyserythropoietic anaemia type I.
AB  - We report, for the first time, an unusual case of congenital anaemia with the
      clinical diagnosis of haemoglobin H disease complicated by morphological features
      at the light and electron microscopy level very similar to those of CDA-I. The
      red cell indices and the globin chain biosynthetic ratio were not characteristic
      of the defective haemoglobin genotype. The haematological, clinical and
      morphological data strongly suggest the novel coexistence of the two defects in a
      patient. The disease is characterised by a unique dyserythropoietic phenotype of
      diagnostic importance, which possibly brings new data regarding the reciprocal
      interaction between the two diseases, especially concerning a specific
      abnormality in globin chain synthesis in CDA-I, as previously suggested.

PMID- 12071944
TI  - Temperature dependence of thermodynamic properties for DNA/DNA and RNA/DNA duplex
      formation.
AB  - A clear difference in the enthalpy changes derived from spectroscopic and
      calorimetric measurements has recently been shown. The exact interpretation of
      this deviation varied from study to study, but it was generally attributed to the
      non-two-state transition and heat capacity change. Although the temperature
      dependent thermodynamics of the duplex formation was often implied, systemic and
      extensive studies have been lacking in universally assigning the appropriate
      thermodynamic parameter sets. In the present study, the 24 DNA/DNA and 41 RNA/DNA
      oligonucleotide duplexes, designed to avoid the formation of hairpin or slipped
      duplex structures and to limit the base pair length less than 12 bp, were
      selected to evaluate the heat capacity changes and temperature-dependent
      thermodynamic properties of duplex formation. Direct comparison reveals that the
      temperature-independent thermodynamic parameters could provide a reasonable
      approximation only when the temperature of interest has a small deviation from
      the mean melting temperature over the experimental range. The heat capacity
      changes depend on the base composition and sequences and are generally limited in
      the range of -160 to approximately -40 cal.mol-1.K-1 per base pair. In contrast
      to the enthalpy and entropy changes, the free energy change and melting
      temperature are relatively insensitive to the heat capacity change. Finally, the
      16 NN-model free energy parameters and one helix initiation at physiological
      temperature were extracted from the temperature-dependent thermodynamic data of
      the 41 RNA/DNA hybrids.

PMID- 12071945
TI  - A chimeric scorpion alpha-toxin displays de novo electrophysiological properties
      similar to those of alpha-like toxins.
AB  - BotXIV and LqhalphaIT are two structurally related long chain scorpion alpha
      toxins that inhibit sodium current inactivation in excitable cells. However,
      while LqhalphaIT from Leiurus quinquestriatus hebraeus is classified as a true
      and strong insect alpha-toxin, BotXIV from Buthus occitanus tunetanus is
      characterized by moderate biological activities. To assess the possibility that
      structural differences between these two molecules could reflect the localization
      of particular functional topographies, we compared their sequences. Three
      structurally deviating segments located in three distinct and exposed loops were
      identified. They correspond to residues 8-10, 19-22, and 38-43. To evaluate their
      functional role, three BotXIV/LqhalphaIT chimeras were designed by transferring
      the corresponding LqhalphaIT sequences into BotXIV. Structural and antigenic
      characterizations of the resulting recombinant chimera show that BotXIV can
      accommodate the imposed modifications, confirming the structural flexibility of
      that particular alpha/beta fold. Interestingly, substitution of residues 8-10
      yields to a new electrophysiological profile of the corresponding variant,
      partially comparable to that one of alpha-like scorpion toxins. Taken together,
      these results suggest that even limited structural deviations can reflect
      functional diversity, and also that the structure-function relationships between
      insect alpha-toxins and alpha-like scorpion toxins are probably more complex than
      expected.

PMID- 12071946
TI  - Cloning and expression of two novel aldo-keto reductases from Digitalis purpurea
      leaves.
AB  - The aldo-keto reductase (AKR) superfamily comprises proteins that catalyse mainly
      the reduction of carbonyl groups or carbon-carbon double bonds of a wide variety
      of substrates including steroids. Such types of reactions have been proposed to
      occur in the biosynthetic pathway of the cardiac glycosides produced by Digitalis
      plants. Two cDNAs encoding leaf-specific AKR proteins (DpAR1 and DpAR2) were
      isolated from a D. purpurea cDNA library using the rat Delta4-3-ketosteroid 5beta
      reductase clone. Both cDNAs encode 315 amino acid proteins showing 98.4%
      identity. DpAR proteins present high identities (68-80%) with four Arabidopsis
      clones and a 67% identity with the aldose/aldehyde reductase from Medicago
      sativa. A molecular phylogenetic tree suggests that these seven proteins belong
      to a new subfamily of the AKR superfamily. Southern analysis indicated that DpARs
      are encoded by a family of at most five genes. RNA-blot analyses demonstrated
      that the expression of DpAR genes is developmentally regulated and is restricted
      to leaves. The expression of DpAR genes has also been induced by wounding,
      elevated salt concentrations, drought stress and heat-shock treatment. The
      isolated cDNAs were expressed in Escherichia coli and the recombinant proteins
      purified. The expressed enzymes present reductase activity not only for various
      sugars but also for steroids, preferring NADH as a cofactor. These studies
      indicate the presence of plant AKR proteins with ketosteroid reductase activity.
      The function of the enzymes in cardenolide biosynthesis is discussed.

PMID- 12071947
TI  - Thermodynamics and kinetics of the cleavage of DNA catalyzed by bleomycin A5.
AB  - Microcalorimetry and UV-vis spectroscopy were used to conduct thermodynamic and
      kinetic investigations of the scission of calf thymus DNA catalyzed by bleomycin
      A5 (BLM-A5) in the presence of ferrous ion and oxygen. The molar reaction
      enthalpy for the cleavage, the Michaelis-Menten constant for calf thymus DNA and
      the turnover number of BLM-A5 were calculated by a novel thermokinetic method for
      an enzyme-catalyzed reaction to be -577 +/- 19 kJ.mol-1, 20.4 +/- 3.8 microm and
      2.28 +/- 0.49 x 10-2 s-1, respectively, at 37.0 degrees C. This DNA cleavage was
      a largely exothermic reaction. The catalytic efficiency of BLM-A5 is of the same
      order of magnitude as that of lysozyme but several orders of magnitude lower than
      those of TaqI restriction endonuclease, NaeI endonuclease and BamHI endonuclease.
      By comparing the molar enthalpy change for the cleavage of calf thymus DNA
      induced by BLM-A5 with those for the scission of calf thymus DNA mediated by
      adriamycin and by (1,10-phenanthroline)-copper, it was found that BLM-A5
      possessed the highest DNA cleavage efficiency among these DNA-damaging agents.
      These results suggest that BLM-A5 is not as efficient as a DNA-cleaving enzyme
      although the cleavage of DNA by BLM-A5 follows Michaelis-Menten kinetics. Binding
      of BLM-A5 to calf thymus DNA is driven by a favorable entropy increase with a
      less favorable enthalpy decrease, in line with a partial intercalation mode
      involved in BLM-catalyzed breakage of DNA.

PMID- 12071948
TI  - Characterization of heparin binding by a peptide from amyloid P component using
      capillary electrophoresis, surface plasmon resonance and isothermal titration
      calorimetry.
AB  - Synthetic peptides based on amino-acid residues 27-38 of human serum amyloid P
      component represent a novel type of heparin binders as they do not contain
      clusters of basic amino acids or other known features associated with protein or
      peptide heparin binding. Here, we characterize the binding using capillary
      electrophoresis (CE), surface plasmon resonance (SPR), and isothermal titration
      calorimetry (ITC). By CE, heparin-binding activity was readily apparent for both
      a regular peptide and a slightly N-terminally modified form, while a sequence
      scrambled peptide had no measurable binding. Dissociation constants in the 1-15
      microm range were estimated, but only a minor part of the binding isotherm was
      covered by the experiments. SPR measurements using immobilized peptides verified
      heparin binding, the range of the binding constants, and the reduced binding of
      the sequence-scrambled peptide. Structurally defined heparin oligosaccharides
      were used to establish that while the tetrasaccharide is too small to exhibit
      strong binding, little difference in binding strength is observed between hexa-
      and tetradeca-saccharides. These experiments also confirmed the almost complete
      lack of activity of the sequence-scrambled peptide. The amino-acid sequence
      dependent binding and the importance of a disulfide bond in the peptide were
      verified by ITC, but the experimental conditions had to be modified because of
      peptide precipitation and ITC yielded significantly weaker binding constants than
      the other methods. While the precise function of the peptide in the intact
      protein remains unclear, the results confirm the specificity of the
      glycosaminoglycan interaction with regard to peptide sequence by applying two
      additional biophysical techniques and showing that the N-terminal part of the
      peptide may be modified without changing the heparin binding capabilities.

PMID- 12071949
TI  - Two 1 : 1 binding modes for distamycin in the minor groove of d(GGCCAATTGG).
AB  - Single-crystal X-ray structure determinations of the complex between the minor
      groove binder distamycin and d(GGCCAATTGG) reveal two 1 : 1 binding modes which
      differ in the orientation of the drug molecule in the minor groove. The two
      crystals were grown from different crystallization conditions and found to
      diffract to 2.38 and 1.85 A, respectively. The structures were refined to
      completion using SHELXL-93, resulting in a residual R factor of 20.30% for the
      2.38-A resolution structure (including 46 water molecules) and 19.74% for the
      1.85-A resolution structure (including 74 water molecules). In both orientations,
      bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug
      and AT base pairs. With a binding site of at least five base pairs, close
      contacts between the terminal distamycin atoms and guanine amino groups are
      inevitable. The detailed nature of several of these interactions was further
      investigated by ab initio quantum chemical methods.

PMID- 12071950
TI  - Expression of uncoupling protein-3 in subsarcolemmal and intermyofibrillar
      mitochondria of various mouse muscle types and its modulation by fasting.
AB  - Uncoupling protein-3 (UCP3) is a mitochondrial inner-membrane protein abundantly
      expressed in rodent and human skeletal muscle which may be involved in energy
      dissipation. Many studies have been performed on the metabolic regulation of UCP3
      mRNA level, but little is known about UCP3 expression at the protein level. Two
      populations of mitochondria have been described in skeletal muscle,
      subsarcolemmal (SS) and intermyofibrillar (IMF), which differ in their
      intracellular localization and possibly also their metabolic role. To examine if
      UCP3 is differentially expressed in these two populations and in different mouse
      muscle types, we developed a new protocol for isolation of SS and IMF
      mitochondria and carefully validated a new UCP3 antibody. The data show that the
      density of UCP3 is higher in the mitochondria of glycolytic muscles (tibialis
      anterior and gastrocnemius) than in those of oxidative muscle (soleus). They also
      show that SS mitochondria contain more UCP3 per mg of protein than IMF
      mitochondria. Taken together, these results suggest that oxidative muscle and the
      mitochondria most closely associated with myofibrils are most efficient at
      producing ATP. We then determined the effect of a 24-h fast, which greatly
      increases UCP3 mRNA (16.4-fold) in muscle, on UCP3 protein expression in
      gastrocnemius mitochondria. We found that fasting moderately increases (1.5-fold)
      or does not change UCP3 protein in gastrocnemius SS or IMF mitochondria,
      respectively. These results show that modulation of UCP3 expression at the mRNA
      level does not necessarily result in similar changes at the protein level and
      indicate that UCP3 density in SS and IMF mitochondria can be differently affected
      by metabolic changes.

PMID- 12071951
TI  - Structural determination of the O-chain polysaccharide from Agrobacterium
      tumefaciens, strain DSM 30205.
AB  - Agrobacterium tumefaciens is a Gram-negative, phytopathogenic bacterium and is
      characterized by an unique mode of action on dicotyledonous plants: it is able to
      genetically modify the host, and because of this feature, it is used as a tool
      for transgenic plants. Many experiments have demonstrated that
      lipopolysaccharides (LPSs) play an important role for the disease development, as
      they are involved in the adhesion process of the bacterium on the plant cell
      wall. Despite the wealth of information on the role of LPS on phytopathogenesis,
      the present paper appears as the first report on the molecular primary structure
      of the O-chain produced from Agrobacterium. Its repeating unit was determined by
      means of chemical and spectroscopical analysis, and has the following structure:
      (3)-alpha-D-Araf-(1-->3)-alpha-l-Fucp-(1-->.

PMID- 12071952
TI  - Potential active-site residues in polyneuridine aldehyde esterase, a central
      enzyme of indole alkaloid biosynthesis, by modelling and site-directed
      mutagenesis.
AB  - In the biosynthesis of the antiarrhythmic alkaloid ajmaline, polyneuridine
      aldehyde esterase (PNAE) catalyses a central reaction by transforming
      polyneuridine aldehyde into epi-vellosimine, which is the immediate precursor for
      the synthesis of the ajmalane skeleton. The PNAE cDNA was previously
      heterologously expressed in E. coli. Sequence alignments indicated that PNAE has
      a 43% identity to a hydroxynitrile lyase from Hevea brasiliensis, which is a
      member of the alpha/beta hydrolase superfamily. The catalytic triad, which is
      typical for this family, is conserved. By site-directed mutagenesis, the members
      of the catalytic triad were identified. For further detection of the active
      residues, a model of PNAE was constructed based on the X-ray crystallographic
      structure of hydroxynitrile lyase. The potential active site residues were
      selected on this model, and were mutated in order to better understand the
      relationship of PNAE with the alpha/beta hydrolases, and as well its mechanism of
      action. The results showed that PNAE is a novel member of the alpha/beta
      hydrolase enzyme superfamily.

PMID- 12071953
TI  - A complex fruit-specific type-2 ribosome-inactivating protein from elderberry
      (Sambucus nigra) is correctly processed and assembled in transgenic tobacco
      plants.
AB  - Fruits of elderberry (Sambucus nigra) express small quantities of a type-2
      ribosome-inactivating protein with an exclusive specificity towards the
      NeuAc(alpha2,6)Gal/GalNAc disaccharide and a unique molecular structure typified
      by the occurrence of a disulfide bridge between the B-chains of two adjacent
      protomers. A cDNA clone encoding this so-called Sambucus nigra fruit specific
      agglutinin I (SNA-If) was isolated and expressed in tobacco (Samsun NN) under the
      control of the 35S cauliflower mosaic virus promoter. Characterization of the
      purified protein indicated that the recombinant SNA-If from tobacco leaves has
      the same molecular structure and biological activities as native SNA-If from
      elderberry fruits, demonstrating that transgenic tobacco plants are fully capable
      of expressing and correctly processing and assembling a type-2 ribosome
      inactivating protein with a complex molecular structure. None of the
      transformants showed a phenotypic effect, indicating that the ectopically
      expressed SNA-If does not affect the viability of the tobacco cells. Bioassays
      further demonstrated that none of the transgenic lines exhibited a decreased
      sensitivity to infection with tobacco mosaic virus suggesting that the elderberry
      type-2 RIP SNA-If does not act as an antiviral agent in planta.

PMID- 12071954
TI  - Escherichia coli small heat shock proteins, IbpA and IbpB, protect enzymes from
      inactivation by heat and oxidants.
AB  - To examine functions of two small heat shock proteins of Escherichia coli, IbpA
      and IbpB, we constructed His-IbpA and His-IbpB, in which a polyhistidine tag was
      fused to the N-terminals. Both purified His-IbpA and His-IbpB formed multimers,
      which have molecular masses of about 2.0-3.0 MDa and consist of about 100-150
      subunits. They suppressed the inactivation of several enzymes including citrate
      synthase and 6-phosphogluconate dehydrogenase by heat, potassium superoxide,
      hydrogen peroxide and freeze-thawing, but not the inactivation of glyceraldehyde
      3-phosphate dehydrogenase by hydrogen peroxide. Both His-IbpA and His-IbpB
      suppressed enzyme inactivation by various treatments and were also found to be
      associated with their non-native forms. However, both His-IbpA and His-IbpB were
      not able to reactivate enzymes inactivated by heat, oxidants or guanidine
      hydrochloride. When heated to 50 degrees C, each multimeric form of His-IbpA or
      His-IbpB was dissociated to form a monomer for His-IbpA, and an oligomer of about
      one-quarter size for His-IbpB. These structural changes were reversible, as both
      heated proteins regained the multimeric structures after incubation at 25 degrees
      C. However, when exposed to hydrogen peroxide or potassium superoxide, the large
      multimeric forms of His-IbpA and His-IbpB were maintained. The results suggest
      that His-IbpA and His-IbpB suppress the inactivation of enzymes and bind non
      native proteins to protect their structures from heat and oxidants.

PMID- 12071955
TI  - Tryptophan fluorescence study of the interaction of penetratin peptides with
      model membranes.
AB  - Penetratin is a 16-amino-acid peptide, derived from the homeodomain of
      antennapedia, a Drosophila transcription factor, which can be used as a vector
      for the intracellular delivery of peptides or oligonucleotides. To study the
      relative importance of the Trp residues in the wild-type penetratin peptide
      (RQIKIWFQNRRMKWKK) two analogues, the W48F (RQIKIFFQNRRMKWKK) and the W56F (RQI
      KIWFQNRRMKFKK) variant peptides were synthesized. Binding of the three peptide
      variants to different lipid vesicles was investigated by fluorescence. Intrinsic
      Trp fluorescence emission showed a decrease in quantum yield and a blue shift of
      the maximal emission wavelength upon interaction of the peptides with negatively
      charged phosphatidylserine, while no changes were recorded with neutral
      phosphatidylcholine vesicles. Upon binding to phosphatidylcholine vesicles
      containing 20% (w/w) phosphatidylserine the fluorescence blue shift induced by
      the W56F-penetratin variant was larger than for the W48F-penetratin.
      Incorporation of cholesterol into the negatively charged lipid bilayer
      significantly decreased the binding affinity of the peptides. The Trp mean
      lifetime of the three peptides decreased upon binding to negatively charged
      phospholipids, and the Trp residues were shielded from acrylamide and iodide
      quenching. CD measurements indicated that the peptides are random in buffer, and
      become alpha helical upon association with negatively charged mixed
      phosphatidylcholine/phosphatidylserine vesicles, but not with phosphatidylcholine
      vesicles. These data show that wild-type penetratin and the two analogues
      interact with negatively charged phospholipids, and that this is accompanied by a
      conformational change from random to alpha helical structure, and a deeper
      insertion of W48 compared to W56, into the lipid bilayer.

PMID- 12071956
TI  - LRP130, a protein containing nine pentatricopeptide repeat motifs, interacts with
      a single-stranded cytosine-rich sequence of mouse hypervariable minisatellite Pc
      1.
AB  - Recently, we have identified and purified minisatellite DNA binding proteins
      (MNBPs) that bind to the mouse hypervariable minisatellite Pc-1, from NIH3T3
      cells. This study describes the isolation and characterization of a mouse leucine
      rich protein (mLRP130) as one of the MNBPs that binds to the C-rich strand of Pc
      1. The mLRP130 cDNA was demonstrated to encode a polypeptide of 1306 amino-acid
      residues with a deduced molecular mass of 137 kDa, and the mLRP130 mRNA is
      detected in various organs, including heart, brain, liver, skeletal muscle,
      kidneys and testes. The mLRP130 protein has nine copies of pentatricopeptide
      repeat (PPR) motifs that are considered to serve as protein-protein interactions.
      Two forms of the mLRP130 protein were detected in NIH3T3 cells with an
      approximate molecular mass of 140 kDa (mLRP130) and 100 kDa (mLRP130der), and
      were detected mainly in nuclear and cytoplasmic fractions, respectively.
      Immunofluorescence microscopic analysis demonstrated dominant localization of
      mLRP130 at the perinuclear region, and also in the nucleus and cytoplasm with dot
      or squiggle-like staining. The immunoprecipitated mLRP130 bound to the single
      stranded d(CTGCC)8, but not to its complementary G-rich strand of d(GGCAG)8 or
      double-stranded form. Possible biological roles of mLRP130 are discussed in
      association with the stability of minisatellite DNA sequences.

PMID- 12071957
TI  - Purification and characterization of novel chondroitin ABC and AC lyases from
      Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium.
AB  - Two novel chondroitinases, chondroitin ABC lyase (EC 4.2.2.4) and chondroitin AC
      lyase (EC 4.2.2.5), have been purified from Bacteroides stercoris HJ-15, which
      was isolated from human intestinal bacteria with glycosaminoglycan degrading
      enzymes. Chondroitin ABC lyase was purified to apparent homogeneity by a
      combination of QAE-cellulose, CM-Sephadex C-50, hydroxyapatite and Sephacryl S
      300 column chromatography with a final specific activity of 45.7 micromol.min
      1.mg-1. Chondroitin AC lyase was purified to apparent homogeneity by a
      combination of QAE-cellulose, CM-Sephadex C-50, hydroxyapatite and
      phosphocellulose column chromatography with a final specific activity of 57.03
      micromol.min-1.mg-1. Chondroitin ABC lyase is a single subunit of 116 kDa by
      SDS/PAGE and gel filtration. Chondroitin AC lyase is composed of two identical
      subunits of 84 kDa by SDS/PAGE and gel filtration. Chondroitin ABC and AC lyases
      showed optimal activity at pH 7.0 and 40 degrees C, and 5.7-6.0 and 45-50 degrees
      C, respectively. Both chondroitin lyases were potently inhibited by Cu2+, Zn2+,
      and p-chloromercuriphenyl sulfonic acid. The purified Bacteroidal chondroitin ABC
      lyase acted to the greatest extent on chondroitin sulfate A (chondroitin 4
      sulfate), to a lesser extent on chondroitin sulfate B (dermatan sulfate) and C
      (chondroitin 6-sulfate). The purified chondroitin AC lyase acted to the greatest
      extent on chondroitin sulfate A, and to a lesser extent on chondroitin C and
      hyaluronic acid. They did not act on heparin and heparan sulfate. These findings
      suggest that the biochemical properties of these purified chondroitin lyases are
      different from those of the previously purified chondroitin lyases.

PMID- 12071958
TI  - The trans-sialidase from the african trypanosome Trypanosoma brucei.
AB  - Trypanosoma brucei is the cause of the diseases known as sleeping sickness in
      humans (T. brucei ssp. gambiense and ssp. rhodesiense) and ngana in domestic
      animals (T. brucei brucei) in Africa. Procyclic trypomastigotes, the tsetse
      vector stage, express a surface-bound trans-sialidase that transfers sialic acid
      to the glycosylphosphatidylinositol anchor of procyclin, a surface glycoprotein
      covering the parasite surface. Trans-sialidase is a unique enzyme expressed by a
      few trypanosomatids that allows them to scavenge sialic acid from sialylated
      compounds present in the infected host. The only enzyme extensively characterized
      is that of the American trypanosome T. cruzi (TcTS). In this work we identified
      and characterized the gene encoding the trans-sialidase from T. brucei brucei
      (TbTS). TbTS genes are present at a small copy number, at variance with American
      trypanosomes where a large gene family is present. The recombinant TbTS protein
      has both sialidase and trans-sialidase activity, but it is about 10 times more
      efficient in transferring than in hydrolysing sialic acid. Its N-terminus
      contains a region of 372 amino acids that is 45% identical to the catalytic
      domain of TcTS and contains the relevant residues required for catalysis. The
      enzymatic activity of mutants at key positions involved in the transfer reaction
      revealed that the catalytic sites of TcTS and TbTS are likely to be similar, but
      are not identical. As in the case of TcTS and TrSA, the substitution of a
      conserved tryptophanyl residue changed the substrate specificity rendering a
      mutant protein capable of hydrolysing both alpha-(2,3) and alpha-(2,6)-linked
      sialoconjugates.

PMID- 12071959
TI  - The Fc receptor gamma-chain is necessary and sufficient to initiate signalling
      through glycoprotein VI in transfected cells by the snake C-type lectin,
      convulxin.
AB  - There is extensive evidence that FcR gamma-chain couples to the collagen receptor
      glycoprotein VI (GPVI) and becomes phosphorylated on tyrosines upon receptor
      cross-linking. However, it is not established whether this receptor complex is
      sufficient to initiate the signalling cascade. We transfected GPVI and the FcR
      gamma-chain into the human erythroleukaemia cell line K562, which lacks
      detectable expression of GPVI and the FcR gamma-chain. The results show that GPVI
      is unable to signal when expressed alone, despite its surface expression, upon
      stimulation with the snake C-type lectin, convulxin. Coexpression of the FcR
      gamma-chain confers signalling properties on the receptor. Furthermore,
      cotransfection of the FcR gamma-chain and two mutant versions of GPVI shows that
      the transmembrane arginine and cytoplasmic tail of GPVI are necessary for
      association with the FcR gamma-chain. These results demonstrate that
      reconstitution of the GPVI-FcR gamma-chain complex in cells expressing the
      necessary signalling network is sufficient to initiate signalling events in
      response to convulxin and collagen-related peptide.

PMID- 12071960
TI  - Regulation of transcription of the Dnmt1 gene by Sp1 and Sp3 zinc finger
      proteins.
AB  - The Sp family is a family of transcription factors that bind to cis-elements in
      the promoter regions of various genes. Regulation of transcription by Sp proteins
      is based on interactions between a GC-rich binding site (GGGCGG) in DNA and C
      terminal zinc finger motifs in the proteins. In this study, we characterized the
      GC-rich promoter of the gene for the DNA methyltransferase (Dnmt1) that is
      responsible for methylation of cytosine residues in mammals and plays a role in
      gene silencing. We found that a cis-element (nucleotides -161 to -147) was
      essential for the expression of the mouse gene for Dnmt1. DNA-binding assays
      indicated that transcription factors Sp1 and Sp3 bound to the same cis-element in
      this region in a dose-dependent manner. In Drosophila SL2 cells, which lack the
      Sp family of transcription factors, forced expression of Sp1 or Sp3 enhanced
      transcription from the Dnmt1 promoter. Stimulation by Sp1 and Sp3 were
      independent phenomena. Furthermore, cotransfection reporter assays with a p300
      expression plasmid revealed the activation of the promoter of the Dnmt1 gene in
      the presence of Sp3. The transcriptional coactivator p300 interacted with Sp3 in
      vivo and in vitro. Our results indicate that expression of the Dnmt1 gene is
      controled by Sp1 and Sp3 and that p300 is involved in the activation by Sp3.

PMID- 12071961
TI  - EPR characterization of the mononuclear Cu-containing Aspergillus japonicus
      quercetin 2,3-dioxygenase reveals dramatic changes upon anaerobic binding of
      substrates.
AB  - Quercetin 2,3-dioxygenase (2,3QD) is a copper-containing dioxygenase that
      catalyses the oxidation of the flavonol quercetin to 2
      protocatechuoylphloroglucinol carboxylic acid with concomitant production of
      carbon monoxide. In contrast to iron dioxygenases, very little is known about
      copper dioxygenases. We have characterized 2,3QD from the fungus Aspergillus
      japonicus by electron paramagnetic resonance spectroscopy (EPR). At pH 6.0, 2,3QD
      shows a mixture of two EPR species. The major form has parameters typical of type
      2 Cu sites (g// = 2.330, A// = 13.7 mT), the minor one has a more distorted
      geometry (g// = 2.290, A// = 12.5 mT). Anaerobic addition of the substrate
      quercetin results in a different, single species EPR spectrum with g// = 2.336,
      A// = 11.4 mT, parameters, which are in-between those of the type 2 and type 1 Cu
      sites in the Peisach-Blumberg (g// vs. A//) plot. After turnover, a new EPR
      signal is observed, which is ascribed to the carboxylic acid ester product
      complex. This spectrum is similar to that of the native enzyme at pH 10.0 and has
      g-tensor parameters suggesting a trigonal bipyramidal site. Of a variety of
      flavonoids studied, only flavonols are able to bind to the copper centre of
      2,3QD. Nine flavonols with different hydroxylation patterns at the A- and B-ring
      have been analysed. They cluster in two different regions of the Peisach-Blumberg
      plot and show that the presence of a 5-OH group has a large effect on the A//
      parameter. Several differences are noted between A. japonicus 2,3QD and the
      enzyme from A. niger German Collection of Microorganisms 821.

PMID- 12071963
TI  - Substrates modulate the rate-determining step for CO binding in cytochrome
      P450cam (CYP101). A high-pressure stopped-flow study.
AB  - The high-pressure stopped-flow technique is applied to study the CO binding in
      cytochrome P450cam (P450cam) bound with homologous substrates (1R-camphor,
      camphane, norcamphor and norbornane) and in the substrate-free protein. The
      activation volume DeltaV # of the CO on-rate is positive for P450cam bound with
      substrates that do not contain methyl groups. The kon rate constant for these
      substrate complexes is in the order of 3 x 10(6) M(-1) x s(-1). In contrast,
      P450cam complexed with substrates carrying methyl groups show a negative
      activation volume and a low kon rate constant of approximately 3 x 10(4) M(-1) x
      s(-1). By relating kon and DeltaV # with values for the compressibility and the
      influx rate of water for the heme pocket of the substrate complexes it is
      concluded that the positive activation volume is indicative for a loosely bound
      substrate that guarantees a high solvent accessibility for the heme pocket and a
      very compressible active site. In addition, subconformers have been found for the
      substrate-free and camphane-bound protein which show different CO binding
      kinetics.

PMID- 12071962
TI  - Mutations in the docking site for cytochrome c on the Paracoccus heme aa3
      oxidase. Electron entry and kinetic phases of the reaction.
AB  - Introducing site-directed mutations in surface-exposed residues of subunit II of
      the heme aa3 cytochrome c oxidase of Paracoccus denitrificans, we analyze the
      kinetic parameters of electron transfer from reduced horse heart cytochrome c.
      Specifically we address the following issues: (a) which residues on oxidase
      contribute to the docking site for cytochrome c, (b) is an aromatic side chain
      required for electron entry from cytochrome c, and (c) what is the molecular
      basis for the previously observed biphasic reaction kinetics. From our data we
      conclude that tryptophan 121 on subunit II is the sole entry point for electrons
      on their way to the CuA center and that its precise spatial arrangement, but not
      its aromatic nature, is a prerequisite for efficient electron transfer. With
      different reaction partners and experimental conditions, biphasicity can always
      be induced and is critically dependent on the ionic strength during the reaction.
      For an alternative explanation to account for this phenomenon, we find no
      evidence for a second cytochrome c binding site on oxidase.

PMID- 12071965
TI  - Mycobacterium tuberculosis FprA, a novel bacterial NADPH-ferredoxin reductase.
AB  - The gene fprA of Mycobacterium tuberculosis, encoding a putative protein with 40%
      identity to mammalian adrenodoxin reductase, was expressed in Escherichia coli
      and the protein purified to homogeneity. The 50-kDa protein monomer contained one
      tightly bound FAD, whose fluorescence was fully quenched. FprA showed a low
      ferric reductase activity, whereas it was very active as a NAD(P)H diaphorase
      with dyes. Kinetic parameters were determined and the specificity constant
      (kcat/Km) for NADPH was two orders of magnitude larger than that of NADH. Enzyme
      full reduction, under anaerobiosis, could be achieved with a stoichiometric
      amount of either dithionite or NADH, but not with even large excess of NADPH. In
      enzyme titration with substoichiometric amounts of NADPH, only charge transfer
      species (FAD-NADPH and FADH2-NADP+) were formed. At NADPH/FAD ratios higher than
      one, the neutral FAD semiquinone accumulated, implying that the semiquinone was
      stabilized by NADPH binding. Stabilization of the one-electron reduced form of
      the enzyme may be instrumental for the physiological role of this mycobacterial
      flavoprotein. By several approaches, FprA was shown to be able to interact
      productively with [2Fe-2S] iron-sulfur proteins, either adrenodoxin or plant
      ferredoxin. More interestingly, kinetic parameters of the cytochrome c reductase
      reaction catalyzed by FprA in the presence of a 7Fe ferredoxin purified from M.
      smegmatis were determined. A Km value of 30 nm and a specificity constant of 110
      microM(-1) x s(-1) (10 times greater than that for the 2Fe ferredoxin) were
      determined for this ferredoxin. The systematic name for FprA is therefore NADPH
      ferredoxin oxidoreductase.

PMID- 12071964
TI  - Role of conserved residues within helices IV and VIII of the oxaloacetate
      decarboxylase beta subunit in the energy coupling mechanism of the Na+ pump.
AB  - The membrane-bound beta subunit of the oxaloacetate decarboxylase Na+ pump of
      Klebsiella pneumoniae catalyzes the decarboxylation of enzyme-bound biotin. This
      event is coupled to the transport of 2 Na+ ions into the periplasm and consumes a
      periplasmically derived proton. The connecting fragment IIIa and transmembrane
      helices IV and VIII of the beta subunit are highly conserved, harboring residues
      D203, Y229, N373, G377, S382, and R389 that play a profound role in catalysis. We
      report here detailed kinetic analyses of the wild-type enzyme and the beta
      subunit mutants N373D, N373L, S382A, S382D, S382T, R389A, and R389D. In these
      studies, pH profiles, Na+ binding affinities, Hill coefficients, Vmax values and
      inhibition by Na+ was determined. A prominent result is the complete lack of
      oxaloacetate decarboxylase activity of the S382A mutant at Na+ concentrations up
      to 20 mm and recovery of significant activities at elevated Na+ concentrations
      (KNa approximately 400 mm at pH 6.0), where the wild-type enzyme is almost
      completely inhibited. These results indicate impaired Na+ binding to the S382
      including site in the S382A mutant. Oxaloacetate decarboxylation by the S382A
      mutant at high Na+ concentrations is uncoupled from the vectorial events of Na+
      or H+ translocation across the membrane. Based on all data with the mutant
      enzymes we propose a coupling mechanism, which includes Na+ binding to center I
      contributed by D203 (region IIIa) and N373 (helix VIII) and center II contributed
      by Y229 (helix IV) and S382 (helix VIII). These centers are exposed to the
      cytoplasmic surface in the carboxybiotin-bound state of the beta subunit and
      become exposed to the periplasmic surface after decarboxylation of this compound.
      During the countertransport of 2 Na+ and 1 H+ Y229 of center II switches between
      the protonated and deprotonated Na+-bound state.

PMID- 12071966
TI  - Toxicity of substrate-bound amyloid peptides on vascular smooth muscle cells is
      enhanced by homocysteine.
AB  - Tauhe main component of cerebral amyloid angiopathy (CAA) in Alzheimer's disease
      is the amyloid-beta protein (Abeta), a 4-kDa polypeptide derived from the beta
      amyloid protein precursor (APP). The accumulation of Abeta in the basement
      membrane has been implicated in the degeneration of adjacent vascular smooth
      muscle cells (VSMC). However, the mechanism of Abeta toxicity is still unclear.
      In this study, we examined the effect of substrate-bound Abeta on VSMC in
      culture. The use of substrate-bound proteins in cell culture mimics presentation
      of the proteins to cells as if bound to the basement membrane. Substrate-bound
      Abeta peptides were found to be toxic to the cells and to increase the rate of
      cell death. This toxicity was dependent on the length of time the peptide was
      allowed to 'age', a process by which Abeta is induced to aggregate over several
      hours to days. Oxidative stress via hydrogen peroxide (H2O2) release was not
      involved in the toxic effect, as no decrease in toxicity was observed in the
      presence of catalase. However, substrate-bound Abeta significantly reduced cell
      adhesion compared to cells grown on plastic alone, indicating that cell-substrate
      adhesion may be important in maintaining cell viability. Abeta also caused an
      increase in the number of apoptotic cells. This increase in apoptosis was
      accompanied by activation of caspase-3. Homocysteine, a known risk factor for
      cerebrovascular disease, increased Abeta-induced toxicity and caspase-3
      activation in a dose-dependent manner. These studies suggest that Abeta may
      activate apoptotic pathways to cause loss of VSMC in CAA by inhibiting cell
      substrate interactions. Our studies also suggest that homocysteine, a known risk
      factor for other cardiovascular diseases, could also be a risk factor for
      hemorrhagic stroke associated with CAA.

PMID- 12071967
TI  - Differential response of neuronal cells to a fusion protein of ciliary
      neurotrophic factor/soluble CNTF-receptor and leukemia inhibitory factor.
AB  - Ciliary neurotrophic factor (CNTF) displays neurotrophic activities on motor
      neurons and neural cell populations both in vivo and in vitro. On target cells
      lacking intrinsic expression of specific receptor alpha subunits cytokines of the
      IL-6 family only act in the presence of their specific agonistic soluble
      receptors. Here, we report the construction and expression of a CNTF/soluble CNTF
      receptor (sCNTF-R) fusion protein (Hyper-CNTF) with enhanced biological activity
      on cells expressing gp130 and leukemia inhibitory factor receptor (LIF-R), but
      not membrane-bound CNTF-R. At the cDNA level, the C-terminus of the extracellular
      domain of human CNTF-R (amino acids 1-346) was linked via a single glycine
      residue to the N-terminus of human CNTF (amino acids 1-186). Recombinant Hyper
      CNTF protein was expressed in COS-7 cells. Hyper-CNTF efficiently induced dose
      dependent STAT3 phosphorylation and proliferation of BAF-3 cells stably
      transfected with gp130 and LIF-R cDNAs. While on BAF3/gp130/LIF-R cells, Hyper
      CNTF and LIF exhibited similar biological responses, the activity of Hyper-CNTF
      on pheochromocytoma cells (PC12 cells) was quite distinct from that of LIF. In
      contrast to LIF, Hyper-CNTF stimulated neurite outgrowth of PC12 cells in a time-
      and dose-dependent manner correlating with the ability to phosphorylate MAP
      kinases. These data indicate that although LIF and Hyper-CNTF use the same
      heterodimeric receptor complex of gp130 and LIFR, only Hyper-CNTF induces
      neuronal differentiation. The therapeutic potential of Hyper-CNTF as a
      superagonistic neurotrophin is discussed.

PMID- 12071968
TI  - Identification and characterization of the Escherichia coli stress protein UP12,
      a putative in vivo substrate of GroEL.
AB  - Many groups of proteins play important roles in the cell's response to various
      stresses. The molecular chaperone GroEL of Escherichia coli represents one such
      highly conserved family of stress proteins. We have observed that isolated GroEL
      complexes from stationary cultures contain various polypeptides that can be
      released from the chaperonin by GroES and/or ATP, and identified two such
      polypeptides as the proteins GatY and UP12. Whereas GatY had been isolated
      previously, as an in vivo substrate of GroEL, the isolation of UP12 in a complex
      with GroEL was intriguing, because based on sequence similarity it was suggested
      that UP12 might also be a functional stress protein. UP12 belongs to a family of
      universal stress proteins (UspA family), of which UspA itself, and three
      additional paralogues, have been characterized previously. Here we show that UP12
      accumulates under various growth inhibitory conditions and induced by heat shock.
      Furthermore, unlike wild-type cells, a UP12 deletion mutant recovers slowly from
      late stationary growth conditions, and has a marked sensitivity to the toxic
      agent carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Finally,
      coimmunoprecipitation experiments confirmed the initial observation that UP12
      interacts with GroEL. Therefore, we suggest that UP12 may function as a universal
      stress protein, interaction of which with GroEL possibly ensures its proper
      folding state.

PMID- 12071969
TI  - Interaction of bovine coagulation factor X and its glutamic-acid-containing
      fragments with phospholipid membranes. A surface plasmon resonance study.
AB  - The interaction of blood coagulation factor X and its Gla-containing fragments
      with negatively charged phospholipid membranes composed of 25 mol%
      phosphatidylserine (PtdSer) and 75 mol% phosphatidylcholine (PtdCho) was studied
      by surface plasmon resonance. The binding to 100 mol% PtdCho membranes was
      negligible. The calcium dependence in the membrane binding was evaluated for
      intact bovine factor X (factor X) and the fragment containing the Gla-domain and
      the N-terminal EGF (epidermal growth factor)-like domain, Gla-EGFN, from factor
      X. Both proteins show the same calcium dependence in the membrane binding.
      Calcium binding is cooperative and half-maximum binding was observed at 1.5 mm
      and 1.4 mm, with the best fit to the experimental data with three cooperatively
      bound calcium ions for both the intact protein and the fragment. The dissociation
      constant (Kd) for binding to membranes containing 25 mol% PtdSer decreased from
      4.6 microm for the isolated Gla-domain to 1 microm for the fragments Gla-EGFN and
      Gla-EGFNC (the Gla-domain and both EGF-like domains) fragments and to 40 nm for
      the entire protein as zymogen, activated enzyme or in the active-site inhibited
      form. Analysis of the kinetics of adsorption and desorption confirmed the
      equilibrium binding data.

PMID- 12071970
TI  - Determinants of the inhibition of a Taiwan habu venom metalloproteinase by its
      endogenous inhibitors revealed by X-ray crystallography and synthetic inhibitor
      analogues.
AB  - Venoms from crotalid and viperid snakes contain several peptide inhibitors which
      regulate the proteolytic activities of their snake-venom metalloproteinases
      (SVMPs) in a reversible manner under physiological conditions. In this report, we
      describe the high-resolution crystal structures of a SVMP, TM-3, from Taiwan habu
      (Trimeresurus mucrosquamatus) cocrystallized with the endogenous inhibitors
      pyroGlu-Asn-Trp (pENW), pyroGlu-Gln-Trp (pEQW) or pyroGlu-Lys-Trp (pEKW). The
      binding of inhibitors causes some of the residues around the inhibitor-binding
      environment of TM-3 to slightly move away from the active-site center, and
      displaces two metal-coordinated water molecules by the C-terminal carboxylic
      group of the inhibitors. This binding adopts a retro-manner principally
      stabilized by four possible hydrogen bonds. The Trp indole ring of the inhibitors
      is stacked against the imidazole of His143 in the S-1 site of the proteinase.
      Results from the study of synthetic inhibitor analogues showed the primary
      specificity of Trp residue of the inhibitors at the P-1 site, corroborating the
      stacking effect observed in our structures. Furthermore, we have made a detailed
      comparison of our structures with the binding modes of other inhibitors including
      batimastat, a hydroxamate inhibitor, and a barbiturate derivative. It suggests a
      close correlation between the inhibitory activity of an inhibitor and its ability
      to fill the S-1 pocket of the proteinase. Our work may provide insights into the
      rational design of small molecules that bind to this class of zinc
      metalloproteinases.

PMID- 12071971
TI  - Molecular mechanisms underlying SHP-1 gene expression.
AB  - SHP-1, a protein-tyrosine phosphatase with two src-homology 2 domains, is
      expressed predominantly in hematopoietic and epithelial cells and has been
      implicated in numerous signaling pathways as a negative regulator. Two promoters
      direct the expression of human and murine SHP-1, and two types of transcripts (I)
      and (II) SHP-1, are initiated from each of these promoters. The cDNA sequences of
      (I)SHP-1 and (II)SHP-1 are identical except in the 5' untranslated region and in
      the first few coding nucleotides. In this report, we show that promoter usage is
      similar in mouse and human hematopoietic cells, but different in epithelial
      cells. In human epithelial cells, only (I)SHP-1 transcripts were expressed. In
      addition, 4beta-phorbol 12-myristate 13-acetate up-regulates human (I)SHP-1
      transcript expression in SKOV3 cells (an ovarian cancer cell line). Indirect
      evidence suggests that nuclear factor-kappaB might play a role in this induction.
      We also show that a 12-bp repeat in the distal SHP-1 promoter, which directs
      (I)SHP-1 expression, is of functional relevance as deletion of one copy of this E
      box-containing 12-bp repeat resulted in a significant decrease in promoter
      activity. Electrophoretic mobility shift assays and supershift experiments showed
      that the upstream stimulatory factors USF1 and USF2 hetero-dimerize and interact
      with this 12 bp repeat. Our results suggest that USFs which have
      antiproliferative functions might regulate the expression of SHP-1, which itself
      is predominantly a negative growth regulator.

PMID- 12071972
TI  - An active site homology model of phenylalanine ammonia-lyase from Petroselinum
      crispum.
AB  - The plant enzyme phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) shows homology to
      histidine ammonia-lyase (HAL) whose structure has been solved by X-ray
      crystallography. Based on amino-acid sequence alignment of the two enzymes,
      mutagenesis was performed on amino-acid residues that were identical or similar
      to the active site residues in HAL to gain insight into the importance of this
      residues in PAL for substrate binding or catalysis. We mutated the following
      amino-acid residues: S203, R354, Y110, Y351, N260, Q348, F400, Q488 and L138.
      Determination of the kinetic constants of the overexpressed and purified enzymes
      revealed that mutagenesis led in each case to diminished activity. Mutants S203A,
      R354A and Y351F showed a decrease in kcat by factors of 435, 130 and 235,
      respectively. Mutants F400A, Q488A and L138H showed a 345-, 615- and 14-fold
      lower kcat, respectively. The greatest loss of activity occurred in the PAL
      mutants N260A, Q348A and Y110F, which were 2700, 2370 and 75 000 times less
      active than wild-type PAL. To elucidate the possible function of the mutated
      amino-acid residues in PAL we built a homology model of PAL based on structural
      data of HAL and mutagenesis experiments with PAL. The homology model of PAL
      showed that the active site of PAL resembles the active site of HAL. This allowed
      us to propose possible roles for the corresponding residues in PAL catalysis.

PMID- 12071973
TI  - Cellular stresses profoundly inhibit protein synthesis and modulate the states of
      phosphorylation of multiple translation factors.
AB  - We have examined the effects of widely used stress-inducing agents on protein
      synthesis and on regulatory components of the translational machinery. The three
      stresses chosen, arsenite, hydrogen peroxide and sorbitol, exert their effects in
      quite different ways. Nonetheless, all three rapidly ( approximately 30 min)
      caused a profound inhibition of protein synthesis. In each case this was
      accompanied by dephosphorylation of the eukaryotic initiation factor (eIF) 4E
      binding protein 1 (4E-BP1) and increased binding of this repressor protein to
      eIF4E. Binding of 4E-BP1 to eIF4E correlated with loss of eIF4F complexes.
      Sorbitol and hydrogen peroxide each caused inhibition of the 70-kDa ribosomal
      protein S6 kinase, while arsenite activated it. The effects of stresses on the
      phosphorylation of eukaryotic elongation factor 2 also differed: oxidative stress
      elicited a marked increase in eEF2 phosphorylation, which is expected to
      contribute to inhibition of translation, while the other stresses did not have
      this effect. Although all three proteins (4E-BP1, p70 S6 kinase and eEF2) can be
      regulated through the mammalian target of rapamycin (mTOR), our data imply that
      stresses do not interfere with mTOR function but act in different ways on these
      three proteins. All three stresses activate the p38 MAP kinase pathway but we
      were able to exclude a role for this in their effects on 4E-BP1. Our data reveal
      that these stress-inducing agents, which are widely used to study stress
      signalling in mammalian cells, exert multiple and complex inhibitory effects on
      the translational machinery.

PMID- 12071976
TI  - Natural attenuation: extant microbial activity forever and ever?

PMID- 12071974
TI  - IgE reactivity of tandem repeats derived from cockroach allergen, Bla g 1.
AB  - Sensitization to cockroach allergens is associated with the development of
      asthma. Bla g 1 is a German cockroach allergen that shows allergenic cross
      reactivity with American cockroach allergen, Per a 1, and has a molecular
      structure composed of multiple tandem amino-acid repeats. Two consecutive repeats
      are not identical but form a duplex that constitutes a basic molecular unit of
      Bla g 1. By molecular mass, purified natural Bla g 1 would contain approximately
      two duplexes. We investigated the pattern of IgE antibody binding to this
      repeated structure, and whether one or two duplexes are sufficient for IgE
      binding. Recombinant (r)Bla g 1 duplexes were expressed in Escherichia coli and
      in Pichia pastoris, and analyzed for monoclonal antibody and IgE antibody binding
      by ELISA and/or immunoblotting. Optimal rBla g 1 expression was obtained using
      methanol-inducible P. pastoris (> 95% pure protein, yield approximately 48 mg x
      L(-1)), and rBla g 1 was produced as multiple molecular forms of molecular mass
      43, 32, 21 and 6 kDa, that were the result of proteolytic cleavage. There was an
      excellent correlation between IgE antibody binding to natural and recombinant Bla
      g 1 (r = 0.91, n = 29, P < 0.001), and immunoblot analysis showed that a single
      Bla g 1 duplex was sufficient for IgE antibody binding. The rBla g 1 is suitable
      for structural studies and a candidate for clinical use in diagnosis of cockroach
      allergy and development of new forms of immunotherapy.

PMID- 12071977
TI  - Microbial diseases of corals and global warming.
AB  - Coral bleaching and other diseases of corals have increased dramatically during
      the last few decades. As outbreaks of these diseases are highly correlated with
      increased sea-water temperature, one of the consequences of global warming will
      probably be mass destruction of coral reefs. The causative agent(s) of a few of
      these diseases have been reported: bleaching of Oculina patagonica by Vibrio
      shiloi; black band disease by a microbial consortium; sea-fan disease
      (aspergillosis) by Aspergillus sydowii; and coral white plague possibly by
      Sphingomonas sp. In addition, we have recently discovered that Vibrio coralyticus
      is the aetiological agent for bleaching the coral Pocillopora damicornis in the
      Red Sea. In the case of coral bleaching by V. shiloi, the major effect of
      increasing temperature is the expression of virulence genes by the pathogen. At
      high summer sea-water temperatures, V. shiloi produces an adhesin that allows it
      to adhere to a beta-galactoside-containing receptor in the coral mucus, penetrate
      into the coral epidermis, multiply intracellularly, differentiate into a viable
      but-not-culturable (VBNC) state and produce toxins that inhibit photosynthesis
      and lyse the symbiotic zooxanthellae. In black band disease, sulphide is produced
      at the coral-microbial biofilm interface, which is probably responsible for
      tissue death. Reports of newly emerging coral diseases and the lack of
      epidemiological and biochemical information on the known diseases indicate that
      this will become a fertile area of research in the interface between microbial
      ecology and infectious disease.

PMID- 12071978
TI  - A chlorophyll a fluorescence-based Lemna minor bioassay to monitor microbial
      degradation of nanomolar to micromolar concentrations of linuron.
AB  - A plant-microbial bioassay, based on the aquatic macrophyte Lemna minor L.
      (duckweed), was used to monitor biodegradation of nano- and micromolar
      concentrations of the phenylurea herbicide linuron. After 7 days of exposure to
      linuron, log-logistic-based dose-response analysis revealed significant growth
      inhibition on the total frond area of L. minor when linuron concentrations > or =
      80 nM were added to the bioassay. A plant-protective effect was obtained for all
      concentrations > 80 nM by inoculation with either a bacterial consortium or
      Variovorax paradoxus WDL1, which is probably the main actor in this consortium.
      The outcome of the plant-microbe-toxicant interaction was also assessed using
      pulse amplitude-modulated chlorophyll a fluorescence and chlorophyll a
      fluorescence imaging. Linuron toxicity to L. minor became apparent as a
      significant decrease in the effective quantum yield (Delta F/Fm') within 90 min
      after exposure of the plants to linuron concentrations > or = 160 nM. Inoculation
      of the bioassay with the linuron-degrading bacteria neutralized the effect on the
      effective quantum yield at concentrations > or = 160 nM, indicating microbial
      degradation of these concentrations. The chlorophyll a fluorescence-based Lemna
      bioassay described here offers a sensitive, fast and cost-effective approach to
      study the potential of biodegrading microorganisms to break down minute
      concentrations of photosynthesis-inhibiting xenobiotics.

PMID- 12071979
TI  - Changes in archaeal, bacterial and eukaryal assemblages along a salinity gradient
      by comparison of genetic fingerprinting methods in a multipond solar saltern.
AB  - Microbial communities inhabiting a multipond solar saltern were analysed and
      compared using SSU rRNA polymerase chain reaction (PCR)-based fingerprintings
      carried out in parallel by four laboratories. A salinity gradient from seawater
      (3.7%) to NaCl precipitation (37%) was studied for Bacteria, Archaea and Eukarya,
      and laboratories applied their own techniques and protocols on the same set of
      samples. Members of all three domains were retrieved from all salt
      concentrations. Three fingerprinting techniques were used: denaturing gradient
      gel electrophoresis (DGGE), ribosomal internal spacer analysis (RISA), and
      terminal-restriction fragments length polymorphism (T-RFLP). In addition, each
      laboratory used its own biomass collection method and DNA extraction protocols.
      Prokaryotes were addressed using DGGE and RISA with different 'domain-specific'
      primers sets. Eukaryotes were analysed by one laboratory using DGGE and T-RFLP,
      but targeting the same 18S rDNA site. Fingerprints were compared through cluster
      analysis and non-metric multidimensional scaling plots. This exercise allowed
      fast comparison of microbial assemblages and determined to what extent the
      picture provided by each laboratory was similar to those of others. Formation of
      two main, salinity-based groups of samples in prokaryotes (4-15% and 22-37%
      salinity) was consistent for all the laboratories. When other clusters appeared,
      this was a result of the particular technique and the protocol used in each case,
      but more affected by the primers set used. Eukaryotic microorganisms changed more
      from pond to pond; 4-5% and 8-37% salinity were but the two main groups detected.
      Archaea showed the lowest number of bands whereas Eukarya showed the highest
      number of operational taxonomic units (OTUs) in the initial ponds. Artefacts
      appeared in the DGGE from ponds with extremely low microbial richness. On the
      other hand, different 16S rDNA fragments with the same restriction or internal
      transcribed spacer (ITS) length were the main limitations for T-RFLP and RISA
      analyses, respectively, in ponds with the highest OTUs richness. However,
      although the particular taxonomic composition could vary among protocols, the
      general structure of the microbial assemblages was maintained.

PMID- 12071980
TI  - Prokaryotic genetic diversity throughout the salinity gradient of a coastal solar
      saltern.
AB  - Bacterial and archaeal assemblages have been studied in a multipond solar saltern
      using a range of microbial ecology techniques by four laboratories
      simultaneously. These include 16S rDNA sequencing from both denaturing gradient
      gel electrophoresis (DGGE) and clone libraries, and culturing methods. Water
      samples from eight ponds were analysed, covering a salinity range from near sea
      water (4% salt) to saturated sodium chloride (37% salt; ponds called
      crystallizers). Clone libraries focused on ponds with salinity of 8%, 22% and
      32%. Although different cloning strategies were able to retrieve the same type of
      dominant sequences, there were differing degrees of success with less abundant
      sequences. Thus, the use of two sets of primers recovered a higher number of
      phylotypes. Bacterial and archaeal isolates were, however, different from any of
      the retrieved environmental sequences. For Bacteria, most sequences in the 8%
      salt pond were related to organisms of marine origin. Thus, representatives of
      the alpha-, beta-, gamma- and epsilon-subdivisions of Proteobacteria, the
      Cytophaga-Flavobacterium-Bacteroides group (CFB), high-G+C Gram-positive bacteria
      and cyanobacteria were found. In the 22% salt pond, alpha- and gamma
      Proteobacteria, cyanobacteria and CFB were the only groups found, and most of
      them were related to specialized halophilic bacteria. From the 32% salt pond,
      only CFB were found, and most of the sequences retrieved clustered with
      Salinibacter ruber, an extremely halophilic bacterium. A decrease in the richness
      of bacterial genera was therefore apparent along the gradient. Archaea behaved
      quite similarly. In the lowest salinity ponds, sequences were related to
      environmental clones of Marine Archaea Group III (Thermoplasmales relatives) and
      to unclassified branches of Euryarchaeaota. In the 8%, 22% and 32% ponds, most of
      the clones were related to different cultured strains of Halobacteriaceae.
      Finally, most sequences from the crystallizers clustered with the uncultured
      square archaeon SPhT. Crenarchaeaota were not detected. Despite the fact that
      higher prokaryotic richness was apparent in the lower salinity ponds than in the
      crystallizers, the diversity index from clone libraries calculated according to
      Shannon and Weaver did not show this trend. This was because diversity in the
      crystallizers can be considered as 'microdiversity', the co-existence of several
      closely related clones of Bacteria (the S. ruber cluster) and Archaea (the SPhT
      cluster). Regardless of the changes in abundance, both Bacteria and Archaea
      showed the same pattern; as salinity increased, the number of different clusters
      decreased, and only one cluster became dominant. Both clusters, however, showed a
      considerable degree of microdiversity. The meaning of such microdiversity remains
      to be determined.

PMID- 12071983
TI  - Head and neck cancer: a screening strategy.

PMID- 12071981
TI  - Stratification and seasonal stability of diverse bacterial communities in a Pinus
      merkusii (pine) forest soil in central Java, Indonesia.
AB  - In Java, Indonesia, many nutrient-poor soils are intensively reforested with
      Pinus merkusii (pine). Information on nutrient cycles and microorganisms involved
      in these cycles will benefit the management of these important forests. Here,
      seasonal effects on the stratification of bacterial community structure in the
      soil profile of a tropical pine forest are described, and differences in
      bacterial communities are related to chemical and physical soil parameters.
      Culture-independent community profiles of litter, fragmented litter and mineral
      soil layers were made by denaturing gradient gel electrophoresis (DGGE) of 16S
      rDNA-specific polymerase chain reaction (PCR) fragments. The community profiles
      of the different soil layers clustered separately, correlating with significant
      differences in organic matter content between the three layers. The bacterial
      communities appeared to be stable during the wet season of 1998. The drought in
      1997, caused by the El Nino climatic effect, did not influence the bacterial
      communities in fragmentation and mineral soil, although moisture content and
      other soil parameters were markedly lower than in the wet season. However,
      communities in litter were influenced by drought. In the litter layer, the
      moisture content was significantly lower than in the fragmentation and mineral
      layers during the dry season. A clone library was made from a litter sample taken
      during the wet season. Partial sequencing of 74 clones and linking the DGGE
      banding positions of these clones to bands in the DGGE profile of the sample from
      which the clone library was derived showed considerable bacterial diversity.
      Alpha-proteobacteria (40.5% of the clones, of which 57% belonged to the Rhizobium
      Agrobacterium group) and high-G+C content, Gram-positive bacteria (36.5%)
      dominated the clone library.

PMID- 12071984
TI  - Nasal mucosal temperature during respiration.
AB  - One of the most important functions of the nose is heating the inspiratory air.
      The aim of the present study was to measure nasal mucosal temperature at defined
      intranasal sites during respiration, without interruption of nasal breathing. A
      total of 15 healthy volunteers was included in the study. A miniaturized
      thermocouple was used for continuous detection of the septal mucosal temperature
      in the nasal vestibule, the nasal valve area, the anterior turbinate area and the
      nasopharynx during respiration. The highest temperature values were measured at
      the end of expiration, the lowest values at the end of inspiration with a
      statistically significant difference (P < 0.005). Mean mucosal temperature ranged
      from 30.2 +/- 1.7 degrees C to 34.4 +/- 1.1 degrees C. Statistically there were
      significant differences between the detection sites during inspiration and
      expiration (P < 0.05). In our study, the temperature values of the nasal mucosa
      depend on the intranasal detection site and the respiratory cycle. We therefore
      conclude that whenever data of nasal mucosal temperature are published, it is
      absolutely essential to describe the precise site of detection and to give
      information about the time of detection in the respiratory cycle.

PMID- 12071985
TI  - The effect of hyperbaric oxygen on nasal mucociliary transport.
AB  - Nasal mucociliary transport was measured in a group of 30 adult patients (eight
      women and 22 men; age range 21-78 years, mean 47.9 years) treated with hyperbaric
      oxygen (HBO) therapy and in a control group of 32 adult subjects (two women and
      30 men; age range 20-50 years, mean 32.0 years) compressed in a hyperbaric
      chamber without oxygen therapy. The treated patients breathed 100% oxygen at 250
      kPa pressure for 60 min. Subjects from the control group were compressed in the
      hyperbaric chamber at 250 kPa for 70 min. Nasal mucociliary transport was
      measured with the saccharin clearance test. After exposure to HBO, the nasal
      mucociliary transport time was significantly decreased by 26% (P < 0.01) and
      returned to the original value after 24 h (increased by 8.3%, P = 0.25). In the
      control group, compressed in air, there were no statistically significant
      changes. This study shows that simultaneous compression and pure oxygen cause an
      increase in nasal mucociliary transport. The mechanism of activation of
      mucociliary clearance is probably the increased oxygenation of blood plasma and
      enhancement of metabolism in ciliated epithelium.

PMID- 12071986
TI  - Cochlear implantation in the obliterated cochlea.
AB  - We present three cases of acquired deafness, associated with obliterated
      cochleas, in which the apparently radiologically more favourable side was chosen
      for implantation. In the first case, because of unexpected obliteration, only a
      partial insertion was possible. Deteriorating performance and non-auditory
      stimulation of the facial nerve led to removal of the implant and a contralateral
      implantation with full insertion under the same anaesthetic gave a good
      postoperative result. In the second case, CT scanning indicated minimal
      obliteration, but extensive obliteration was encountered at surgery, which
      required double-array insertion with a delayed but satisfactory outcome. In the
      third case, extensive unexpected obliteration was noted at surgery and, in light
      of the experience gained with the first two cases, it was decided not to proceed
      but to explore the contralateral side. At surgery on the contralateral side, a
      patent cochlea was noted with full electrode insertion and an excellent outcome.
      These cases demonstrate a learning curve for this department and our philosophy
      now is to explore the contralateral ear rather than accept a partial insertion.

PMID- 12071987
TI  - Early discharge following nasal pack removal: is it feasible?
AB  - A prospective study of 50 consecutive patients admitted for nasal packing for
      epistaxis reveals that only 20% re-bled after removal of packs and that 96% of
      those recurrences occurred during the first 4 h after pack removal. No patients
      required repacking or blood transfusion. The need for a 24-h observation period
      following nasal pack removal therefore appears not to be required, and the
      implementation of an early discharge policy for patients treated for epistaxis by
      nasal packing is therefore potentially feasible, and would result in significant
      cost savings.

PMID- 12071988
TI  - Bone involvement in chronic rhinosinusitis assessed by 99mTc-MDP bone SPECT.
AB  - To investigate the clinical significance of bone involvement in chronic
      rhinosinusitis, 99mTc-MDP bone single photon emission computed tomography (SPECT)
      was studied in 43 patients diagnosed as having chronic rhinosinusitis.
      Quantitative isotope uptake indices calculated on SPECT were compared between the
      patient and a control group, and between patients with a good postoperative
      outcome and those with a poor outcome. The patient group showed a significantly
      higher isotope uptake than the control group. The uptake of isotope in the
      ethmoid sinus areas in patients who had a poor postoperative outcome was
      significantly higher than those who had a good outcome. Our study suggests that
      patients with chronic rhinosinusitis have apparent bony involvement, and patients
      with more severe bone involvement may have a poorer treatment outcome.

PMID- 12071989
TI  - Sound frequency analysis and the site of snoring in natural and induced sleep.
AB  - The aim of this study was to compare the snoring sounds induced during sleep
      nasendoscopy, and to compare them with those of natural sleep using sound
      frequency spectra. The snoring of 16 subjects was digitally recorded during
      natural and induced sleep, noting the site of vibration during sleep
      nasendoscopy. Patients with palatal snoring during sleep nasendoscopy had a
      median peak frequency at 137 Hz (118 snore samples). The peak frequency of tongue
      base snoring was 1243 Hz (10 snore samples), and simultaneous palate and tongue
      was 190 Hz (six snore samples). The median power ratios were 7, 0.2 and 5
      respectively. The centre frequencies were 371, 1094 and 404 Hz respectively.
      Epiglottic snores had a peak frequency of 490 Hz (five snore samples). Comparison
      of the induced (n = 118) and natural (n = 300) snore samples of the 12 palatal
      snorers showed a significant difference in both the power ratio and centre
      frequencies (P = 0.031 and P = 0.049). The peak frequency position was similar (P
      = 0.34). Our results indicate that induced snores contain a higher frequency
      component of sound, not evident during natural snoring. This is consistent with
      an element of tongue-base snoring. Although there is good correlation generally,
      sleep nasendoscopy may not accurately reflect natural snoring.

PMID- 12071990
TI  - Endoscopic marsupialization of congenital nasolacrimal duct cyst with
      dacryocoele.
AB  - A congenital nasolacrimal duct cyst is an uncommon condition in the newborn
      usually treated by ophthalmologists. Prolapse or expansion of the cyst into the
      nose may lead to respiratory distress and difficulty in feeding as newborns are
      obligate nose breathers, which needs the involvement of the Otolaryngologist in
      diagnosis and management. The authors report a series of 8 children presenting
      with a congenital nasolacrimal duct cyst and dacryocoele and highlight the
      importance of endoscopic nasal examination of newborns presenting with
      respiratory problems. Diagnostic studies included intranasal endoscopy and CT
      scanning of the nasolacrimal system and nose. All the patients were treated by
      endoscopic marsupialization of the cyst. Nasolacrimal duct abnormality should be
      considered in the differential diagnosis of neonatal respiratory distress and
      nasal obstruction. Nasal endoscopy is essential in the work-up of all children
      with nasal obstruction and respiratory distress. CT scanning is the investigative
      method of choice. Endoscopic marsupialization followed by lacrimal duct
      irrigation is effective in the treatment of congenital nasolacrimal duct cyst and
      results in complete resolution of symptoms.

PMID- 12071991
TI  - Facial pain following sinonasal surgery or facial trauma.
AB  - The case notes of 22 patients who reported facial pain after sinonasal surgery or
      trauma out of a cohort of 973 patients seen in a rhinology clinic were reviewed
      retrospectively. This group included 10 patients who had undergone endoscopic
      sinus surgery and four who had suffered facial fractures. None of the patients
      reported any facial pain before surgery or trauma. In only one case was there any
      evidence, clinically, endoscopically, or radiologically, of any paranasal sinus
      disease and when this resolved with nasal medical treatment the pain remained.
      The treatment of these patients' facial pain centred on the use of neurological
      medical treatment. One third of the patients responded to low-dose amitriptyline,
      a further third showed some response to other pharmacological agents including
      carbamazepine, and the remaining third showed no response. These cases illustrate
      the characteristics and management of facial pain after sinonasal surgery and
      highlight the importance of medical neurological treatment in the absence of any
      objective evidence of sinus disease.

PMID- 12071992
TI  - Increased post-tonsillectomy secondary haemorrhage with disposable instruments:
      an audit cycle.
AB  - The objective of the audit was to examine the increased morbidity associated with
      elective tonsillectomy with single-use instruments in a district general hospital
      in England. Retrospective audit of consecutive case notes of 145 patients who
      underwent tonsillectomy in a 6-week period after the introduction of single-use
      instruments was carried out. The main outcome measure was incidence of secondary
      haemorrhage. In total, 9.5% of patients required re-admission indicated by
      secondary haemorrhage, 4% required emergency surgery and 43% of the total group
      had haemostasis achieved with ties. None of these was re-admitted. Out of the
      total group, 57% had haemostasis achieved with single-use bipolar forceps; 16.8%
      of these patients were re-admitted, with 7% of this group requiring emergency
      surgery to control the haemorrhage. Animal tissue experiments and design analysis
      of the single-use bipolar diathermy highlighted the deficiencies of the initial
      single-use bipolar diathermy. This was replaced by a new design of single-use
      diathermy forceps. A second audit was performed which revealed a significant
      reduction in postoperative morbidity. Complications associated with the
      introduction of new instruments can be identified by repeated audit cycles.

PMID- 12071993
TI  - The quality of life impact of dysphonia.
AB  - Dysphonia can affect social life and employment, but formal studies of its
      general health impact are lacking. The aims of this study were (i) to compare
      self-rated general health status as measured by the SF-36 in a large cohort of
      dysphonic patients with those from normative groups; and (ii) to examine the
      differential impact of dysphonia on the various health status domains. The 163
      dysphonic voice clinic attendees (38 men, 125 women) were drawn from recruits to
      a prospective trial of speech therapy efficacy. The Short-Form 36 (SF-36) scores
      were compared with published data on 744 age-matched healthy controls. Patients
      with dysphonia had significantly poorer self-reported health than the controls on
      all eight SF-36 subscales (limitation of physical activity P < 0.05; other seven,
      all P < 0.001, Student's t-test). We thus conclude that dysphonia in patients
      without obvious laryngeal disease has an adverse impact on all health status
      subscales as measured by the SF-36. The study provides further evidence for the
      inclusion quality of life measures in otolaryngology baseline and outcome
      assessments.

PMID- 12071994
TI  - Squamous carcinoma of the external auditory canal: a different approach.
AB  - Squamous carcinoma of the external ear canal is a rare disease and a challenge to
      treat. Some controversy exists regarding the best options for treatment. Reported
      5-year survival varies between 35% and 63%. Since 1976, we have adopted a
      conservative approach to these tumours, with patients undergoing a specific
      protocol of meticulous tumour debulking followed by a course of repeated topical
      5-fluoro-uracil (5-FU) cream application and necrotectomy. Data was collected
      prospectively. From 1976 to 1998, 23 patients underwent primary treatment
      according to our protocol. Nine patients had T1 disease whereas six had T2 and
      eight had T3 disease. The 5- and 10-year overall survivals were 74% and 60%
      respectively. These results compare very favourably with those in the literature
      and surgical debulking with topical 5-FU and necrotectomy remains our primary
      treatment of choice for squamous cell carcinoma of the external auditory canal.

PMID- 12071995
TI  - Columelloplasty: a new suture technique to correct caudal septal cartilage
      dislocation.
AB  - Deviation of the nasal septum is a common finding in patients with nasal
      obstruction and, when such deviation is severe, a septoplasty or submucous
      resection with or without turbinate reduction is commonly recommended for the
      relief of the patient's symptoms. In cases where there is anterior subluxation of
      the septum, the caudal margin frequently presents on one or either side of the
      midline at the external nares. We report a simple suture technique which, when
      subluxation is not severe, will correct this caudal displacement. The technique
      can either be used as an adjunct to conventional septoplasty or it can be
      undertaken as an isolated procedure in patients having routine rhinoplasty.

PMID- 12071996
TI  - A comparison of cocaine and 'co-phenylcaine' local anaesthesia in flexible
      nasendoscopy.
AB  - Cocaine is widely used as a local anaesthetic in the nose. However, it is
      potentially toxic, a known drug of addiction, and its spray delivery devices can
      theoretically transfer infection. This two-part study investigates a less toxic
      alternative, 5% lidocaine and 0.5% phenylephrine ('co-phenylcaine') solution,
      presented in a disposable spray. In the first part, the efficacy of co
      phenylcaine was assessed in 25 healthy volunteers. Serial acoustic rhinometry
      showed a significant, sustained nasal decongestion after co-phenylcaine
      administration. Visual analogue scale (VAS) scores in response to a painful nasal
      stimulus confirmed a significant anaesthetic effect. In the second part, co
      phenylcaine was compared with 10% cocaine spray in a randomized double-blind
      trial in 74 patients undergoing out-patient transnasal fibrescopic laryngoscopy.
      VAS pain ratings and nasal inspiratory peak flow recordings showed no difference
      between the two solutions. No adverse effects were noted. It is concluded that co
      phenylcaine is an excellent alternative to cocaine nasal spray.

PMID- 12071997
TI  - Mandibular osteoradionecrosis: reconstructive surgery.
AB  - Osteoradionecrosis of the mandible is a serious complication following
      radiotherapy of head and neck cancers. A retrospective study of 20
      reconstructions of mandibular defects due to osteoradionecrosis was performed.
      Various osseocutaneous free flaps were used: upper lateral arm (n = 5), radial
      forearm (n = 1), iliac crest (n = 4) and fibula (n = 7). Four grafts had a
      condylar prosthesis, and for seven grafts fixation was accomplished with a
      reconstruction plate. In three patients the mandibular defect was reconstructed
      using a bridging plate only. We defined a successful reconstruction as a graft or
      plate that did not need removal. Success was noted in 15 out of 20 patients,
      giving an overall success rate of 75%. For the free grafts alone (n = 17),
      successful reconstruction was achieved in 15 patients (88%). Two fibular grafts
      were lost owing to exposure and infection, as well as all three alloplastic
      reconstructions. Minor postoperative complications were observed in 11 patients
      (58%).

PMID- 12071998
TI  - Publishing trends in otolaryngology in the UK.

PMID- 12072001
TI  - Systemic photoprotection with alpha-tocopherol (vitamin E) and beta-carotene.
AB  - Cutaneous photodamage is partly mediated via oxidative pathways and there is
      evidence to suggest that antioxidants within the skin may have a photoprotective
      effect. Antioxidant activity is provided by a number of naturally occurring
      substances including alpha-tocopherol (vitamin E) and beta-carotene, whose
      effects are mediated by their capacity to quench singlet oxygen, scavenge free
      radicals and prevent the formation of free radicals. Beta-carotene has been used
      as treatment for various photosensitivity disorders for more than 30 years. The
      main indication for its use is in the treatment of the photosensitivity
      associated with erythropoietic protoporphyria. A role for beta-carotene in the
      prevention of non-melanoma skin cancer has yet to be demonstrated despite
      clinical research activity in this area. The role for alpha-tocopherol as a
      photoprotective agent is less clear-cut and it has yet to be established as
      treatment either for conditions characterized by photosensitivity or as an agent
      for preventing chronic photodamage or cutaneous malignancy.

PMID- 12072002
TI  - Patients' strategies for coping with psoriasis.
AB  - There is a paucity of research on the types of strategies that patients with
      psoriasis use to cope with the impact of their condition. By contrast there are a
      number of studies assessing coping by patients with nondermatological disease.
      The purpose of the present study was to examine strategies for coping in patients
      with psoriasis and investigate whether they differ as compared with normal
      controls and patients with other major medical diseases. Two hundred and fifty
      patients with a definite dermatologist-confirmed diagnosis of psoriasis
      participated in this cross-sectional study. Patients were assessed by psoriasis
      area severity index and all patients completed the COPE questionnaire and
      psoriasis disability index. Sixty healthy, control participants completed the
      COPE questionnaire for comparison purposes. Mean COPE scores from patients with
      psoriasis were also compared with published COPE scores from other medical
      diseases. The coping strategies most frequently used by patients with psoriasis
      were acceptance, planning, active coping and positive reinterpretation. The least
      frequently used were alcohol and nonprescription drugs, religion, and denial of
      their condition. Despite reporting greater disability, patients with severe
      psoriasis did not significantly differ from those with mild/moderate disease in
      their use of particular forms of coping strategies. Patients with psoriasis as a
      whole tended to use significantly less active coping strategies, planning,
      positive reinterpretation and humour when compared with normal controls. There
      was marked similarity in the frequency of use of particular coping strategies
      between patients with psoriasis and patients with other medical conditions.
      Similar types of coping strategies are utilized by patients regardless of whether
      their illness is visible (psoriasis) invisible (chronic fatigue syndrome, atrial
      fibrillation), has significant physical impairment (spinal cord injury), or is
      life-threatening (cancer, and myocardial infarction). It appears that illness
      brings with it a generic form of coping that may require shaping to fit the
      individual demands of diseases such as psoriasis.

PMID- 12072003
TI  - Urticarial intolerance reaction to cetirizine.
AB  - The paradoxical acute exacerbation of pre-existing chronic idiopathic urticaria
      accompanied by intense generalized pruritus, facial oedema, and dyspnoea in a 36
      year-old-woman 3-4 h after a single oral dose of 10 mg cetirizine (Zyrtec
      tablets), suggested the presence of an underlying intolerance reaction. However,
      a type I hypersensitivity reaction also had to be excluded. Detailed allergy
      testing supported the view that the patient had suffered an intolerance reaction
      to cetirizine. This is the third known case of most probably a nonallergic
      generalized urticaria following the administration of cetirizine, a drug with
      extensive usage worldwide. However a type I sensitization to cetirizine is indeed
      possible, as has been demonstrated in this research with the verification of
      cetirizine-specific IgE antibodies in one of the control sera.

PMID- 12072005
TI  - Acquired scrotal lymphangiomas: successful treatment with cutting diathermy and
      carbon dioxide laser.
AB  - We report a case of unusually severe, scrotal lymphangiomas that have been
      treated successfully with the novel combination of cutting diathermy and carbon
      dioxide laser.

PMID- 12072004
TI  - Tuberculosis verrucosa cutis on the sole of the foot.
AB  - We report an unusual case of tuberculosis verrucosa cutis on the plantar aspect
      of the foot that had been present for more than 40 years in a 62-year-old Indian
      man. He had a grade IV positive Heaf test and a normal chest radiograph.
      Mycobacterium tuberculosis was successfully cultured from the third biopsy taken
      from the lesion. This case demonstrates the indolent nature of the lesion and
      stresses the importance of taking adequate biopsies for microbiological culture
      when there is a high index of suspicion for M. tuberculosis. The diagnosis of
      tuberculosis verrucosa cutis should be based on history and evolution of the
      disease, cardinal morphological features and histopathological characteristics.
      Response to anti-tuberculosis drugs may be of assistance.

PMID- 12072006
TI  - Uncommon vascular naevi associated with focal acantholytic dyskeratosis.
AB  - Cutis marmorata telangiectatica congenita and vascular twin naevi are rare
      vascular anomalies in which focal acantholytic dyskeratosis is usually not
      observed. We describe a 44-year-old-man who presented for evaluation of skin
      lesions that had been present since birth. Physical examination revealed anaemic
      macules adjacent to a naevus telangiectaticus on the chest. Naevus anaemicus was
      also seen on the shoulders, arms, and left leg. There was bluish-reddish
      reticulate marking of the skin and cutaneous atrophy. Shortening and hypoplasia
      of the left leg was observed. Histologic examination of two biopsy specimens
      revealed focal acantholytic dyskeratosis. In vivo confocal laser scanning
      microscopy showed dilated capillaries and vessels of the upper dermal plexus in
      the telangiectatic and decreased capillary blood flow in the anaemic skin sites.
      The findings were consistent with a diagnosis of cutis marmorata telangiectatica
      congenita, vascular twin naevi, and incidental focal acantholytic dyskeratosis.
      The particularities of the present case are the following: firstly, the
      association of two rare vascular anomalies to which the genetic concept of
      mosaicism can be applied; secondly, the occurrence of incidental focal
      acantholytic dyskeratosis in sites of vascular naevi.

PMID- 12072007
TI  - Cutaneous zosteriform squamous cell carcinoma metastasis arising in an
      immunocompetent patient.
AB  - Cutaneous metastases from internal malignancies or primary skin cancers are
      uncommon, and a zosteriform pattern is very rare. Histologically, these cutaneous
      metastases usually appear as malignant epithelial cells located throughout the
      dermis or subcutaneous fat and without connection to the overlying epidermis. The
      presence of melanocytes in such lesions is atypical. Moreover, although
      zosteriform cutaneous metastases of cutaneous squamous cell carcinoma have
      previously been described in immunosuppressed patients, they have not been
      reported in immunocompetent patients. We report an unusual case of a woman with
      cutaneous hyperchromic zosteriform metastases, clinically mimicking a metastatic
      melanoma but appearing histologically as epidermotropic and pigmented metastases
      of a cutaneous squamous cell carcinoma.

PMID- 12072008
TI  - Two cases of late onset Ota's naevus.
AB  - Ota's naevus is among the dermal melanocytoses that show a distinct pattern
      involving skin innervated by the trigeminal nerve. Most cases present at birth or
      manifest clinically in early childhood. Cases of acquired lesions in adult onset
      have been reported rarely. We present two cases of late onset Ota's naevus which
      were confirmed by skin biopsies. Both patients underwent Q-switched alexandrite
      laser treatment with a dose of 8.0 J/cm2 given four or five times at 6 weekly
      intervals and showed some improvement.

PMID- 12072009
TI  - An unusual presentation of diffuse granuloma annulare in an HIV-positive patient 
      immunohistochemical evidence of predominant CD8 lymphocytes.
AB  - Over the past decade there have been several reports in the literature of
      atypical forms of granuloma annulare (GA) occurring in HIV positive patients. We
      now report a case of diffuse granuloma annulare in an HIV positive patient with
      unusual clinical and immunohistological features. Our patient presented with a
      persistent extensive macular erythematous eruption on his face and upper trunk
      with bizarre sparing around the nipples and axillae. The histology showed an
      interstitial pattern of GA, with a predominance of CD8 positive cells, in
      contrast to the usual CD4 positive infiltrate typically seen in GA.

PMID- 12072010
TI  - Squamous cell carcinoma arising in a venous ulcer as a complication of the
      Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay (KT) syndrome is a vascular malformation characterized by a
      port-wine stain, varicose veins and hypertrophy of the affected limb. Ulceration
      is considered an uncommon complication of KT syndrome and occurrence of skin
      cancer has been previously reported only in one case. We observed a case of KT
      syndrome in a 48-year-old woman who developed a large ulcer and a squamous cell
      carcinoma on the affected leg.

PMID- 12072011
TI  - Coexistence of CD30-positive anaplastic large cell lymphoma and mycosis
      fungoides.
AB  - Primary cutaneous T-cell lymphomas, including lymphomatoid papulosis, mycosis
      fungoides and CD30+ anaplastic large cell lymphoma (ALCL) overlap
      clinicopathologically and form part of a spectrum of lymphoproliferative
      disorders. There have been several case reports of these diseases coexisting. We
      describe a 59-year-old Korean man who presented with a recurrent, solitary CD30+
      ALCL of 25 years' duration as well as patch stage mycosis fungoides of 11 years'
      duration. Such occurrences may represent different clinical manifestations of the
      same clonal T-cell abnormality, and provide further insight into the pathogenesis
      of these related disorders.

PMID- 12072012
TI  - Palmar filiform hyperkeratosis (FH) associated with underlying pathology?
AB  - We describe two patients with palmar filiform hyperkeratosis, characterized by
      multiple thin spiny keratotic projections on the palms. The condition has been
      associated with an underlying malignancy in some cases. One patient has
      myelofibrosis, an association not previously described. In addition we describe a
      further patient with filiform hyperkeratoses of both palms and soles with no
      associated underlying disorder. In view of the relatively high risk of underlying
      malignancy occurring in patients with filiform hyperkeratosis, these patients
      should always be investigated fully.

PMID- 12072013
TI  - Heat shock proteins and the skin.
AB  - Heat shock proteins are of fundamental importance in cutaneous biology, from
      protection against UV-induced damage to wound healing and repair. Heat shock
      proteins have important regulatory roles in the control of apoptosis, regulation
      of steroid aporeceptors, kinases, and other protein remodelling events. They are
      also implicated in the control of cell growth, and as such, are potential targets
      for cancer diagnosis and treatment. Currently, emphasis is being placed on the
      potential use of these proteins in the prevention and treatment of disease.
      Therapeutic manipulation of these proteins may ultimately lead to novel
      treatments for diseases as diverse as melanoma to epidermolysis bullosa.

PMID- 12072014
TI  - Serum cytokine levels in atopic dermatitis.
AB  - Elevated IgE responses and eosinophilia observed in patients with atopic
      dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2)
      cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production.
      However, the cross-regulation of Th1/Th2 derivation and function in AD patients
      are incompletely characterized. Therefore, we investigated serum levels of
      several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in
      patients with AD to assess their possible relationships to the severity of
      disease. Serum IL-18 levels in AD patients were significantly higher than those
      in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs.
      144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly
      correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R)
      levels, and showed a tendency to correlate with clinical severity scores and
      serum IgE levels. IL-2 levels showed a significantly inverse correlation with
      serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These
      results suggest the value of serum IL-18 levels as a parameter of AD activity and
      may support a possible role for IL-18 in the pathogenesis of AD. The inverse
      correlation between IgE levels and IL-2 levels suggests that IgE production may
      be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12
      levels with IL-10 levels may support the previous reports that show the induction
      of IL-10 production by human natural killer cells and/or T cells stimulated with
      IL-12 in vitro.

PMID- 12072015
TI  - Beneficial effects of synthetic phospholipid polymer, poly(2-methacryloyloxyethyl
      phosphorylcholine-co-n-butyl methacrylate), on stratum corneum function.
AB  - The effects of a newly synthesized phospholipid polymer, poly(2
      methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) [poly(MPC-co
      BMA)], on the water barrier function and water-holding capacity of the stratum
      corneum were examined by measuring transepidermal water loss (TEWL) and
      electrical conductance of the skin surface. On the backs of four NC mice, the
      epidermal permeability barrier was abrogated by cellophane tape stripping 30
      times. The skin was then treated with 0.1% poly(MPC-co-BMA) or distilled water
      twice daily for the following 3 days. Poly(MPC-co-BMA) reduced TEWL significantly
      compared with the control after the first treatment (P = 0.044) and this effect
      was observed for 3 days. In human skin, water-holding capacity was measured at 5,
      10, 15, 30 min and 1, 2, and 4 h after the application of poly(MPC-co-BMA) or
      distilled water to both volar forearms of 21 healthy volunteers. Skin treated
      with poly(MPC-co-BMA) showed significantly greater ability to retain water at all
      time points. Poly(MPC-co-BMA) is the first synthetic material that can enhance
      both the water barrier function and water-holding capacity of the stratum
      corneum. Our results indicate that this substance may be useful clinically in the
      treatment of dry skin.

PMID- 12072016
TI  - Associations between human leukocyte antigens and leprosy in the Turkish
      population.
AB  - Leprosy is a chronic infection caused by an intracellular microorganism. Genetic
      predisposition to both disease susceptibility and to host immunological response
      has been postulated for many years. The aim of this study was to determine
      whether there is HLA-linked susceptibility to leprosy and its different types.
      HLA-class I (A, B, C) and II (DR, DQ) antigen frequencies in 80 patients with
      leprosy (35 borderline lepromatous, 25 lepromatous, 15 borderline tuberculoid,
      five tuberculoid) were compared with those in 120 healthy individuals. HLA-class
      I antigens A9, A10, A32, B5, B21, Bw4, Bw6, Cw1, Cw2 and HLA-class II antigens
      DR9, DR10, DRw52, DQ1, DQ3 were found to be significantly more frequent in
      patients with leprosy, whereas HLA-class I antigens A3, B44, B49 and HLA-class II
      antigen DQ5 were so in controls. However, there was no significant difference in
      HLA-class I and II antigen frequencies between subtypes of leprosy. HLA-A null
      antigen was found to have weak expression in patients with leprosy. In
      conclusion, factors other than HLA-class I and class II antigens may have a more
      critical role in the pathophysiology of leprosy infection in man.

PMID- 12072017
TI  - AL amyloidosis is not present as an incidental finding in cutaneous biopsies of
      patients with multiple myeloma.
AB  - Multiple myeloma (MM) is a monoclonal B-cell neoplasm characterized by autonomous
      proliferation of immunoglobulin-secreting plasma cells that are capable of
      synthesizing amyloidogenic light chains resulting in AL amyloidosis. Clinically
      occult AL amyloid deposition may occur in up to 31% of patients with MM. The
      prognosis of combined amyloidosis and MM is improving with new therapeutic
      options. Thus it is imperative that patients with MM be screened for amyloidosis.
      Sixty-six consecutive skin biopsies from patients with MM and the diagnosis of
      graft vs. host disease (GVHD) were stained with Congo red and assessed for the
      presence of amyloid deposition. Twelve cases that had amyloid deposition in other
      tissue and had a cutaneous biopsy were also stained with Congo red and assessed
      for the presence of amyloid deposition. None of the 66 biopsies of GVHD, and none
      of the 12 cases that had documented amyloid deposition in other tissue showed
      evidence of amyloid deposition in the cutaneous biopsies. In the absence of
      specific cutaneous manifestations of amyloidosis, it is unlikely that
      amyloidogenic light chain deposition in the skin would be found. Type I collagen
      may appear similar to amyloid, both by light microscopy and fluorescence, after
      staining with Congo red. Thus care must be taken not to confuse type I collagen
      autofluorescence with positivity for amyloid when assessing skin biopsies stained
      with Congo red.

PMID- 12072018
TI  - A recurrent mutation in the loricrin gene underlies the ichthyotic variant of
      Vohwinkel syndrome.
AB  - Vohwinkel syndrome (VS) is a family of genodermatoses which exhibits extensive
      clinical and genetic heterogeneity. Here, we studied a pedigree originating from
      the UK with typical features of the ichthyotic variant of VS and identified a
      recurrent insertion mutation in the loricrin gene resulting in a mutant
      polypeptide with an unusual C terminus. Functional studies in transgenic mice
      have shown that the accumulation of mutant loricrin in the nucleus appears to
      interfere with the later stages of epidermal differentiation, thereby explaining
      the clinical manifestations of ichthyosis, keratoderma and pseudoainhum. Our
      findings extend the body of evidence implicating mutations in the loricrin gene
      as the underlying cause of VS.

PMID- 12072019
TI  - Symmetrical hypopigmentation following triamcinolone injection for de Quervain's
      tenosynovitis.

PMID- 12072020
TI  - Cutaneous larva migrans in the west coast of Scotland.

PMID- 12072021
TI  - Patients' and doctors' assessment of skin disease handicap.

PMID- 12072022
TI  - Adult primary cutaneous Langerhans' cell histiocytosis mimicking nodular prurigo.

PMID- 12072036
TI  - Clinical use of GnRH analogues.

PMID- 12072037
TI  - Orbital irradiation for thyroid-associated orbitopathy: conventional dose, low
      dose or no dose?

PMID- 12072038
TI  - Isoflavone supplementation and endothelial function in menopausal women.
AB  - OBJECTIVE: Despite strong observational evidence for a beneficial role of
      oestrogen in cardiovascular disease, recent trial results suggest that hormone
      replacement therapy (HRT) may have adverse effects in menopausal women with
      established coronary heart disease. Isoflavones are oestrogen analogues found in
      plants with oestrogen-like properties and, because of a favourable side-effect
      profile, may be ideal alternatives to HRT with respect to cardiovascular
      benefits. Endothelial function is a marker of cardiovascular health. We aimed to
      determine the effect of isoflavones on endothelial function using the brachial
      artery reactivity test. DESIGN AND MEASUREMENTS: Twenty-nine healthy menopausal
      women underwent entry and exit brachial artery reactivity testing following
      randomization to 2 weeks of an oral soy isoflavone concentrate containing 80 mg
      of soy isoflavones (Archer Daniel Midland Inc., IL, USA) or placebo. RESULTS: At
      study exit, there was no difference between placebo and isoflavone groups with
      respect to flow-mediated dilation (%FMD(max)), change (entry to exit) in
      %FMD(max) or response to nitroglycerine (%TNG). Subgroup analyses assessing lipid
      and oestrogen effects did not produce any significant results. CONCLUSIONS: These
      results suggest that short-term oral isoflavone supplements do not improve
      endothelial function in healthy menopausal women.

PMID- 12072039
TI  - Prospective 10-year study of the determinants of bone density and bone loss in
      normal postmenopausal women, including the effect of hormone replacement therapy.
AB  - OBJECTIVE: To prospectively assess bone density and the factors determining the
      rate of bone loss over a 10-year period of postmenopausal life. DESIGN:
      Prospective, observational study. METHODS: One hundred and four normal White
      postmenopausal women, baseline mean age 59 years (range 47-71 years) completed
      the study (mean duration of follow-up 10.2 years, range 9.4-10.6 years). None had
      diseases or were taking medications affecting bone metabolism at entry to the
      study. Information was collected on medical, fracture and smoking history,
      alcohol use, dietary calcium intake and physical activity. Body composition and
      bone density were measured by dual-energy X-ray absorptiometry at baseline and at
      10 years. Biochemical, haematological and hormonal analyses were performed.
      RESULTS: Twenty-four percent of the women started hormone replacement therapy
      (HRT) during the study period; most of these remained on therapy at follow-up.
      The mean duration of therapy was 6.6 years (range 2.8-10.4 years). The use of HRT
      was associated with significant gains in bone density (total body + 3.0%,
      trochanter + 4.2%, Ward's triangle + 4.4%, spine + 10.5%) and a significant
      reduction in vertebral fracture risk [standardized risk ratio compared with non
      HRT users 0.42 (confidence interval 0.18-0.83)]. HRT use was not associated with
      greater weight gain than that occurring in other members of the cohort. The
      baseline and follow-up bone densities in the non-HRT users were highly correlated
      (0.82 < or = r < or = 0.91, P < or = 0.0001) and baseline bone density accounted
      for the majority of the variance in the 10-year results. Multivariate analyses
      showed that the independent correlates of rate of change of bone density were
      weight and fat mass (both baseline values and changes during follow-up), time
      after menopause, sex hormone concentrations, urinary calcium loss, PTH levels and
      haemoglobin concentration (which may reflect nutrition and health). CONCLUSIONS:
      Bone density is highly predictable over an extended period of time in normal
      postmenopausal women. Maintenance of body weight and good health reduce bone
      loss. HRT is effective for treating osteoporosis, with improvement in bone
      density and reduction in vertebral fractures. Good compliance with HRT long-term
      is achievable. These findings are relevant to deciding the frequency of bone
      density measurement, and in advising women regarding prevention and treatment of
      postmenopausal bone loss.

PMID- 12072040
TI  - (99m)Technetium pentavalent dimercaptosuccinic acid scintigraphy in the follow-up
      of clinically nonfunctioning pituitary adenomas after radiotherapy.
AB  - BACKGROUND: It is still difficult to differentiate pituitary adenoma remnants
      from postradiotherapy fibrosis by computed tomography (CT) or magnetic resonance
      imaging (MRI), especially in patients with clinically nonfunctioning pituitary
      adenomas (NFA), lacking circulating markers to follow disease progression or
      cure. OBJECTIVE: We investigated the usefulness of scintigraphy with technetium
      99m pentavalent dimercaptosuccinic acid [(99m)Tc(V)DMSA], shown previously to
      detect most pituitary GH- and PRL-secreting adenomas and NFA, with tumour-to
      background ratios (T/B) as high as 25-fold. PATIENTS: Eighteen patients with NFA
      (study group), 10 patients with GH- and three patients with PRL-secreting
      adenomas (control group), all of whom had undergone previous surgery. DESIGN: The
      study was an open longitudinal design. Pituitary CT/MRI and (99m)Tc(V)DMSA
      scintigraphy was performed before and 1, 3 and 5 years after conventional
      radiotherapy. Tumour size was measured as maximal diameter of the residual
      lesion, while uptake of (99m)Tc(V)DMSA was measured as a T/B ratio. RESULTS: At
      study entry, pituitary (99m)Tc(V)DMSA uptake was found in 13 NFA (72.2%), seven
      GH-secreting (70%) and all PRL-secreting adenomas; remnant tumour was documented
      by CT/MRI in all 31 patients. Maximal remnant diameter was significantly higher
      in patients with positive (13.3 +/- 0.9 mm) than in those with negative
      scintigraphy (7.0 +/- 0.3 mm, P < 0.001). During the 5-year follow-up
      postradiotherapy, a significant decrease in (99m)Tc(V)DMSA uptake (9.7 +/- 0.8
      vs. 3.2 +/- 0.5, P < 0.0001) occurred in all but three patients. Two NFA patients
      died of tumour invasion 19 and 36 months after radiotherapy and one acromegalic
      patient had no change in his hormone levels. In the eight negative patients (five
      NFA and three GH), scintigraphy remained negative throughout follow-up. A
      remarkable shrinkage of the remnant tumour was observed in both the patients with
      negative (from 7.0 +/- 0.3 to 1.9 +/- 0.6 mm, P < 0.001) and in those with
      positive scintigraphy (from 13.3 +/- 0.9 to 7.3 +/- 0.6 mm, P < 0.001). At the
      end of the study, CT/MRI showed evident remnant tumour in 13 of 16 NFA (81.2%),
      nine GH-secreting (90%) and all three prolactinomas (100%), while the
      scintigraphy was negative (T/B < 1) or faintly positive (T/B 1-2) in eight of 16
      NFA (50%), five GH-secreting (50%) and one prolactinoma (33.3%). CONCLUSIONS:
      Functional imaging of pituitary remnant adenomas (> 10 mm in size) by
      (99m)Tc(V)DMSA depicts viable pituitary adenoma remnants. This approach may be of
      clinical value in patients with clinically nonfunctioning adenomas to monitor the
      effects of radiotherapy.

PMID- 12072041
TI  - What is the role of the insulin-like growth factor system in the pathophysiology
      of cancer cachexia, and how is it regulated?
AB  - OBJECTIVE AND BACKGROUND: The cancer cachexia syndrome is characterized by
      anorexia, weight loss with muscle wasting and increased energy expenditure. It is
      associated with increased morbidity and mortality, but its aetiology is poorly
      understood and no effective therapeutic intervention is available. It may result
      from an imbalance between the activity or effect of anabolic and catabolic
      hormones, mediated by the inflammatory cytokines. IGF-I is a potent anabolic
      agent, with therapeutic potential. Our objective was to investigate the role and
      regulation of the IGF system in cancer cachexia. DESIGN AND PATIENTS: We set up a
      prospective study of 30 patients with newly diagnosed unresectable non-small cell
      lung cancer, together with a cross-sectional comparison group of healthy
      volunteers. MEASUREMENTS: We examined the relationship between aspects of the IGF
      system, including IGFBP-3 proteolysis (using Western ligand and immunoblotting
      and an in vitro IGFBP-3 protease assay); the inflammatory cytokines and their
      soluble receptors; and food intake and nutritional status (including biochemical
      and anthropometric assessments). RESULTS: Although we did not observe a marked
      reduction in food intake in the cancer patients, the majority lost weight and
      functionally important lean body mass. We observed GH resistance in the cancer
      patients, and intermittent proteolysis of IGFBP-3, which correlated with the
      circulating interleukin-6 (IL-6) concentration. The pattern of IGFBP-3
      proteolysis was unusual, with a prominent 17-kDa fragment. Less IGFBP-3
      proteolysis was associated with more weight loss, suggesting that this could be a
      protective counter-regulatory mechanism, increasing IGF-I bioavailability to the
      tissues. CONCLUSIONS: Cancer cachexia in humans is a complex condition. Patients
      tend to be GH resistant. The significance of the intermittent increases in IGFBP
      3 proteolysis, which may be regulated by IL-6, remains uncertain. A better
      understanding of the pathophysiology should enable the development of novel
      therapeutic approaches.

PMID- 12072042
TI  - Dysregulation of iodothyronine deiodinase enzyme expression and function in human
      pituitary tumours.
AB  - OBJECTIVE: Thyroid hormones (THs) perform essential roles in pituitary function.
      They regulate anterior pituitary hormone secretion and are also key determinants
      of pituitary cell proliferation and differentiation. The critical role of
      deiodinase enzymes, which serve as prereceptor regulators of TH action, remains
      largely unexplored. Three deiodinase enzymes metabolize active and inactive THs
      and thereby determine tissue concentrations of the biologically active ligand,
      tri-iodothyronine (T3). We hypothesized that aberrant expression of deiodinase
      enzymes and/or altered enzyme activity in pituitary tumours may change tissue
      concentrations of THs and influence their growth and secretory characteristics.
      STUDY DESIGN AND PATIENTS: We studied 105 pituitary tumours and 10 normal
      pituitaries for expression of deiodinase enzyme mRNAs encoding types 1 (D1), 2
      (D2) and 3 (D3) using real-time RT-PCR. Enzyme activity data from 20 pituitary
      samples were also obtained. RESULTS: Pituitary tumours expressed significantly
      increased D3 mRNA (6.5-fold, P < 0.0005) compared with normal pituitaries. D2
      mRNA was also increased 2.6-fold (P = 0.005) in pituitary tumours compared with
      normals. The rare TSH-secreting pituitary tumour subtype expressed a 13.1-fold
      excess of D3 mRNA and reduced D2 mRNA (0.1-fold of normal pituitaries). D2 mRNA
      expression in ACTH-secreting tumours was similarly reduced to 0.1-fold that in
      normal pituitaries. CONCLUSIONS: Pituitary adenomas express abnormal levels of
      deiodinase enzymes compared to normal pituitaries. These abnormalities may have
      functional consequences on pituitary tumour growth. In the case of TSH-secreting
      pituitary adenomas, the observed pattern of deiodinase mRNA expression may
      explain the 'resistance' of this tumour type to TH feedback.

PMID- 12072043
TI  - Oestrogen supplementation attenuates responses to psychological stress in elderly
      men rendered hypogonadal after treatment for prostate cancer.
AB  - BACKGROUND: We have shown previously that oestrogens attenuate cardiovascular and
      hormonal responses to stress in perimenopausal women. The cardiovascular role of
      oestrogens in men is uncertain, despite preliminary evidence that endogenous
      oestrogens produced by aromatization of androgenic precursors are of
      physiological importance; hypogonadal men have very low levels of circulating
      oestrogen. METHODS: We therefore studied the haemodynamic and hormonal responses
      to a standardized laboratory mental stress test in 12 men (mean age 68.9 +/- 2.6
      SEM years) rendered hypogonadal as a result of treatment for prostatic cancer,
      before and after 8 weeks of oestrogen supplementation (oestradiol valerate 1 mg
      daily, n = 7) or placebo (n = 5). The stress was administered as a standard
      mental arithmetic test of 10 minutes' duration. Blood pressure, cortisol and ACTH
      were measured at baseline, and following 5 minutes and 10 minutes of stress, and
      ACTH again at 25 minutes on both days. Noradrenaline and adrenaline responses to
      mental stress, as well as changes in total body and forearm spillover of
      noradrenaline and noradrenaline clearance, were also measured. RESULTS: Oestrogen
      supplementation was well tolerated, with minimal adverse effects. Mean oestradiol
      levels increased from < 30 pmol/l to 308 +/- 65 pmol/l after oestrogen treatment.
      Oestradiol significantly attenuated the mental stress-induced increase in both
      systolic and diastolic blood pressures. Oestradiol also attenuated mental stress
      induced increases in ACTH, cortisol and adrenaline, but did not influence either
      total body or forearm spillover of noradrenaline. Responses to stress were
      unchanged after administration of placebo. CONCLUSIONS: We conclude that
      oestrogen supplementation in men rendered hypogonadal as a result of treatment
      for prostate cancer is well tolerated and significantly attenuates blood pressure
      and hormonal responses to psychological stress. These findings suggest the need
      for further studies to examine a possible clinical role for oestrogen treatment
      in hypogonadal men.

PMID- 12072044
TI  - Testicular dose and fertility in men following I(131) therapy for thyroid cancer.
AB  - OBJECTIVE: Young adults with differentiated thyroid cancer are treated with high
      doses of radioiodine and have an excellent long-term prognosis. However, there is
      limited information on the effects of this treatment on the gonads and fertility
      in male patients. We have reviewed the outcome of treatment in our centre with
      respect to male fertility. We have also assessed directly the radiation dose
      received by the testes. DESIGN: Retrospective analysis of males attending the
      thyroid clinic at the Royal Marsden Hospital for treatment of differentiated
      thyroid cancer. A prospective study was also performed to assess radiation dose
      to testes in 14 consecutive patients attending for thyroid cancer treatment.
      PATIENTS: Males under the age of 40 years at the time of treatment with a minimum
      of 3 years follow-up. MEASUREMENTS: Number of children fathered by patients and
      number of congenital malformations. For the prospective study: gonadal function
      assessed by serum FSH, LH and testosterone measurements; radiation dose to the
      testes (Gy) measured by thermoluminescent dosimetry. RESULTS: Fertility was
      assessed in 122 men with a median follow-up of 21 years (range 3-39) of whom 93
      were under active follow-up. One hundred and six children were fathered by 59
      patients; the remainder had no wish to have children. No major malformations were
      reported. Of these 59 patients, 12 had received a single 3 GBq ablation dose, 19
      had been treated with up to 14 GBq radioiodine and 28 had received up to 44 GBq.
      In 14 patients followed prospectively, the median estimated radiation dose to
      each testis was 6.4 cGy following 3 GBq, 14.1 cGy following 5.5 GBq and 21.2 cGy
      following 9.2 GBq. There was a transient elevation in serum FSH after radioiodine
      which normalized within 9 months from the last administration. CONCLUSIONS:
      Radioiodine treatment for thyroid cancer may result in transient impairment of
      gonadal function. The radiation dose absorbed by the testis after a single
      ablative dose of radioiodine is well below that associated with permanent damage
      to germinal epithelium and the risk of infertility in these patients is minimal.
      Patients requiring multiple administrations for persistent or metastatic thyroid
      cancer may be at greater risk of gonadal damage although even in this group, we
      found no evidence of infertility.

PMID- 12072045
TI  - Sympathetic nerve hyperactivity is associated with increased peripheral vascular
      resistance in hypopituitary patients with growth hormone deficiency.
AB  - OBJECTIVE: Hypopituitary patients with untreated GH deficiency have increased
      cardiovascular mortality. Sustained vasoconstriction is an important factor in
      the development of hypertension and insulin resistance. This study was designed
      to see whether peripheral vascular resistance was increased in subjects with GH
      deficiency and to examine the mechanisms involved. METHODS: Nine patients with GH
      deficiency and nine matched control subjects were studied. Calf vascular
      resistance was measured by venous occlusion plethysmography and sympathetic
      vasoconstrictor nerve activity by peroneal microneurography. RESULTS: Subjects
      with GH deficiency had a significantly lower blood flow (by 31%) and higher
      vascular resistance (by 48%) than the control group. In addition, they had a
      significantly higher sympathetic vasoconstrictor activity (by 67%) and this
      correlated with the vascular resistance (r = 0.45; P < 0.04). CONCLUSIONS:
      Patients with GH deficiency have an increased peripheral vascular resistance that
      is contributed to by an increase in central sympathetic vasoconstrictor discharge
      to the peripheral vasculature. This could be important in the development of
      cardiovascular disease in this condition.

PMID- 12072046
TI  - Endocrine responses to ghrelin in adult patients with isolated childhood-onset
      growth hormone deficiency.
AB  - OBJECTIVE: Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the
      GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS.
      Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also
      displays significant stimulatory effects on lactotroph and corticotroph
      secretion. It has been hypothesized that isolated GH deficiency (GHD) could
      reflect hypothalamic impairment that would theoretically involve defect in
      ghrelin activity. PATIENTS: In the present study, we verified the effects of
      ghrelin (1 microg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients
      with isolated severe GHD [five males and one female, age (mean +/- SEM) 24.7 +/-
      2.6 years, BMI 25.7 +/- 2.7 kg/m2]. In all patients, the GH response to insulin
      induced hypoglycaemia (ITT, 0.1 IU regular insulin i.v.) and GH releasing hormone
      (GHRH) (1 microg/kg i.v.) + arginine (ARG, 0.5 g/kg i.v.) was also studied. The
      hormonal responses in GHD were compared with those in age-matched normal subjects
      (NS, seven males, age 28.6 +/- 2.9 years, BMI 22.1 +/- 0.8 kg/m2). RESULTS: IGF-I
      levels in GHD were markedly lower than in NS (69.8 +/- 11.3 vs. 167.9 +/- 19.2
      microg/l, P < 0.003). Ghrelin administration induced significant increase in GH,
      PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was
      higher (P < 0.05) than that to GHRH + ARG, which, in turn, was higher (P < 0.05)
      than that to ITT (9.2 +/- 4.1 vs. 5.3 +/- 1.7 vs. 1.4 +/- 0.4 microg/l). These GH
      (1 microg/l = 2 mU/l) responses in GHD were markedly lower (P < 0.0001) than
      those in NS (ghrelin vs. GHRH + ARG vs. ITT 92.1 +/- 16.7 vs. 65.3 +/- 8.9 vs.
      17.7 +/- 3.5 microg/l). In GHD, the highest individual peak GH response to
      ghrelin was markedly lower than the lowest peak GH response in NS (28.5 vs. 42.9
      microg/l). GHD and NS showed overlapping PRL (1 microg/l = 32 mU/l) (10.0 +/- 1.4
      vs. 14.9 +/- 2.2 microg/l), ACTH (22.3 +/- 5.3 vs. 18.7 +/- 4.6 pmol/l) and
      cortisol responses (598.1 +/- 52.4 vs. 486.9 +/- 38.9 nmol/l). CONCLUSIONS: This
      study shows that ghrelin is one of the most powerful provocative stimuli of GH
      secretion, even in those patients with isolated severe GHD. In this condition,
      however, the somatotroph response is markedly reduced while the lactotroph and
      corticotroph responsiveness to ghrelin is fully preserved, indicating that this
      endocrine activity is fully independent of mechanisms underlying the GH-releasing
      effect. These results do not support the hypothesis that ghrelin deficiency is a
      major cause of isolated GH deficiency but suggest that ghrelin might represent a
      reliable provocative test to evaluate the maximal GH secretory capacity provided
      that appropriate cut-off limits are assumed.

PMID- 12072047
TI  - Preliminary evidence that an endogenous retroviral long-terminal repeat (LTR13)
      at the HLA-DQB1 gene locus confers susceptibility to Addison's disease.
AB  - OBJECTIVE: Addison's disease is associated with particular haplotypes of the
      human leucocyte antigen (HLA) region [DQA1*0501-DQB1*0201 (DQ2) and DQA1*0301
      DQB1*0302 (DQ8)]. This locus harbours several human endogenous retroviral (HERV)
      long-terminal repeats (LTR). LTRs within the HLA region have been shown to confer
      additional susceptibility to type 1 diabetes and rheumatoid arthritis. DESIGN: We
      investigated the role of LTR3 and LTR13, both of which are located adjacent to
      the DQB1 gene, in Addison's disease. PATIENTS: Eighty-seven patients and 160
      controls were genotyped for HLA-DQA, -DQB, and the presence or absence of LTR3
      and LTR13. RESULTS: Significantly more patients' HLA alleles than those of
      controls carried the LTR13 insertion (19.0% vs. 10.6%, P = 0.0143), whereas there
      was only a trend for LTR3 (allele-wise chi-squared test: P = 0.0941). Both, LTR3
      and LTR13 are in strong linkage disequilibrium with DQ8, which itself was
      significantly more frequent in patients than in controls (29.9% vs. 15.0%, P =
      0.0089). However, significantly more alleles of DQ8+ patients than of DQ8+
      controls carried the LTR13 insertion (44.2% vs. 18.8%, P = 0.0119), whereas we
      did not observe any difference for LTR3 in the DQ8+ subset (30.5 vs. 23.1%, P =
      0.9416). CONCLUSIONS: We have found preliminary evidence that the endogenous
      retroviral element DQ-LTR13, but not LTR3, is associated with Addison's disease.
      LTR13 appears to enhance HLA-DQ8 mediated disease risk. This retroviral insertion
      therefore might represent a novel susceptibility factor in Addison's disease, but
      these findings need to be confirmed in a larger data set.

PMID- 12072048
TI  - Long-term effects of androgen deprivation therapy in prostate cancer patients.
AB  - BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men and
      has an increasing incidence. In 1999, 37 000 men died from PCa in the USA.
      Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in
      the treatment of recurrent and metastatic PCa by inducing medical castration,
      rendering these men hypogonadal. Because hypogonadism in men is associated with a
      wide range of complications, we attempted to determine the effects of long-term
      ADT in men with PCa. METHODS: We conducted a cross-sectional study at a tertiary
      care centre to determine the effect of ADT on lean body mass (LBM), muscle
      strength, bone mineral density (BMD), sexual function, and quality of life (QOL)
      in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were
      undergoing medical castration with GnRH agonists for at least 12 months prior to
      the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa
      who were post prostatectomy and/or radiotherapy but had not yet undergone ADT
      (non-ADT group); and (3) 20 age-matched normal men who were healthy and
      ambulatory (control group). RESULTS: Men on ADT had castrate levels of serum
      total testosterone (P < 0.0001), free testosterone (P < 0.0001) and oestradiol (P
      < 0.0001), which were significantly lower than in the other groups. Total body (P
      = 0.03) and lumbar spine (P < 0.0001) BMD was significantly lower in patients on
      ADT compared to other groups and was associated with higher levels of urinary N
      telopeptide (P = 0.02). The ADT group had higher fat mass compared to the other
      groups (P = 0.0001) and significantly reduced upper body strength (P = 0.001)
      when compared to non-ADT patients. The ADT group had lower overall scores on
      Watt's Sexual Function Questionnaire compared to other groups (P = 0.0001), in
      particular a decrease in desire, arousal and frequency of spontaneous early
      morning erections. The ADT group also had lower overall QOL scores, resulting in
      significant limitation of physical function (P = 0.001), role limitation (P =
      0.02) and perception of physical health (P = 0.004). CONCLUSIONS: This study
      suggests that osteoporosis, unfavourable body composition, sexual dysfunction and
      reduced quality of life are seen in patients receiving androgen deprivation
      therapy for at least 12 months. Longitudinal studies in this patient population
      will shed further light on the timing of the development and the extent of these
      complications. Meanwhile, this information will assist both physicians and
      patients with prostate cancer to make informed decisions regarding androgen
      deprivation therapy.

PMID- 12072049
TI  - High prevalence and increasing incidence of Addison's disease in western Norway.
AB  - OBJECTIVE: Estimates of the prevalence of Addison's disease in Caucasians have
      varied from 39 to 117 per million. We have carried out an epidemiological study
      to obtain a confident point prevalence estimate in the Norwegian population for
      the end of 1999, and to find out whether the incidence is changing. PATIENTS AND
      METHODS: The patients were identified by a search through registers of 10
      hospitals and consultant endocrinologists serving a population of 916 000. The
      completeness of the list was tested by a survey of general practitioners in one
      district, and by the member list of the local Addison Association in another
      district. RESULTS: We identified 128 patients with Addison's disease (59 men and
      69 women), yielding a prevalence of 140 per million. Recorded mean incidence in
      the past decade was 0.62 per 100,000 per year. Fifty-one patients (40%) had
      concomitant endocrine diseases. The aetiology was almost exclusively idiopathic
      or autoimmune. CONCLUSIONS: We found a higher prevalence of Addison's disease in
      western Norway than has previously been reported anywhere. Our findings support
      the hypothesis of a rising incidence of autoimmune adrenal insufficiency.

PMID- 12072050
TI  - Thyrotoxicosis induced by alpha-interferon therapy in chronic viral hepatitis.
AB  - BACKGROUND AND OBJECTIVE: It has been well documented that treatment of chronic
      hepatitis B and C infection with interferon alpha (IFN-alpha) can lead to the
      induction of thyroid autoantibodies and hypothyroidism. Thyrotoxicosis, however,
      is less frequently observed and less well characterized. PATIENTS AND METHODS: We
      reviewed the medical records of patients who developed thyrotoxicosis while
      receiving IFN-alpha for either chronic hepatitis B or C infection at Westmead
      Hospital between 1996 and March 2001. RESULTS: Ten patients (four males and six
      females) were found to have biochemical thyrotoxicosis. The patients could be
      divided into two groups with different characteristics. The first group consisted
      of six patients who had clinical manifestations consistent with Graves' disease,
      with either diffuse uptake in thyroid scintigraphy and/or positive thyroid
      stimulating antibodies. They all required prolonged treatment with antithyroid
      medications. The second group included three patients who had transient
      thyrotoxicosis, with progression to hypothyroidism after resolution of
      thyrotoxicosis. CONCLUSION: Our study suggests that IFN therapy may provoke two
      different forms of thyrotoxicosis: a Graves' disease picture or a biphasic
      thyroiditis pattern. The two entities should be differentiated, as they have
      different implications for treatment.

PMID- 12072051
TI  - Changes in adiposity and excess body weight correlate with growth responses but
      not with decreases in low-density lipoprotein cholesterol levels during GH
      treatment in GH-deficient children.
AB  - BACKGROUND AND AIMS: GH has profound effects on body composition and lipid
      metabolism in children as well as in adults. The relationship between such
      metabolic effects and the growth-promoting effects of GH has not been studied
      thoroughly in children with GH deficiency. This prospective study was designed to
      determine the relationship between growth and lipid metabolism during long-term
      GH treatment. PATIENTS AND METHODS: Twenty-two boys with idiopathic GH deficiency
      were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and
      serum low-density lipoprotein (LDL) cholesterol levels were determined every 6
      months during 3 years of GH treatment. RESULTS: After 3 years of GH treatment,
      the mean height SD score had increased significantly from -2.70 SD to -1.59 SD (P
      < 0.0001), while the mean %OW and LDL cholesterol level had decreased
      significantly from 7.0% to 1.3% (P < 0.0001) and from 2.69 mmol/l to 2.04 mmol/l
      (P < 0.0001), respectively. The mean %BF fell significantly from 15.5% to 11.1%
      during the first 6 months of GH treatment (P < 0.0001). The 6-month reduction in
      %BF correlated significantly with the 3-year increase in height SD score (r = 
      0.58, P = 0.008). The decrease in %OW also correlated negatively with the change
      in height SD score (r = -0.48, P = 0.03). However, there was no correlation
      between the changes in LDL cholesterol levels and those in %BF, %OW or height SD
      score. CONCLUSION: We conclude that the growth-promoting effects of GH correlate
      significantly with the reductions in %BF and %OW but not with the decrease in LDL
      cholesterol level in children with GH deficiency. The changes in LDL cholesterol
      did not correlate with any of the changes in body composition parameters,
      suggesting that the various actions of GH may have different mechanisms of
      regulation.

PMID- 12072052
TI  - Polysomnographic findings in five adult patients with pituitary insufficiency
      before and after cessation of human growth hormone replacement therapy.
AB  - OBJECTIVE: We observed the new onset of severe obstructive sleep apnoea syndrome
      (OSAS) in an adult male patient during human growth hormone (hGH) replacement
      therapy. This prompted us to evaluate the potential influence of hGH substitution
      therapy on sleep in middle-aged men. DESIGN: A longitudinal study. SUBJECTS: Five
      male patients (aged 44-56 years, median age 54 years) with postoperative
      pituitary insufficiency given hGH replacement therapy for 1-2 years (median dose
      2.0 U/day; median IGF-I serum concentration 351 microg/l) and 6 months after
      cessation of hGH treatment (median IGF-I level 77 microg/l - 1 microg/l = 0.131
      nmol/l). MEASUREMENTS: Polysomnographic studies were performed, and the following
      parameters were determined: time in bed (TIB), sleep period time (SPT), total
      sleep time (TST), sleep efficiency (SE = TST/TIB), sleep stage 1 onset latency
      (SL), different sleep stages [W (wake), S1, S2, SWS (slow wave sleep = S3 + S4)
      and REM; % of SPT], stage shifts per hour of SPT (SS/h), stage shifts to W/h of
      SPT [A/h (awakening)], index of apnoea and hypopnoea events per hour of TST
      (AH/h), arousals from apnoea and hypopnoea per hour of TST (Ar/h), index of
      obstructive (OAH/h), central (CAH/h) and mixed (MAH/h) events of apnoea and
      hypopnoea per hour of TST and minimal desaturation (MD). RESULTS: Median baseline
      results were: TIB, 479 min; SPT, 465 min; TST, 405 min; SE, 77%; SL, 8.5 min; W,
      18.9%; S1, 8.2%; S2, 52.7%; REM, 13.5%; SS/h, 17.7; A/h, 2.8; AH/h, 11.9; Ar/h,
      4.4; MD, 80%. These parameters did not change significantly after cessation of
      hGH treatment. In contrast, median SWS decreased significantly from 33 min (7.1%)
      to 7.5 min (1.8%; P = 0.03). Median OAH/h decreased significantly from 4.4 to 0.1
      (P = 0.03) whereas CAH/h increased from 6.3 to 14.6 (P = 0.03) after cessation of
      hGH. Correspondingly, one patient with OSAS improved markedly whereas another
      patient developed new and asymptomatic central SAS after cessation of hGH.
      CONCLUSION: This study showed that hGH replacement therapy influenced sleep
      reaction in a complex way in middle-aged men; cessation of treatment was
      associated with a significant decrease in slow wave sleep and a shift from
      obstructive to central apnoea and hypopnoea.

PMID- 12072053
TI  - Increased prevalence of heterozygous 21-OH germline mutations in patients with
      adrenal incidentalomas.
AB  - OBJECTIVE: As a result of the widespread use and the enhanced quality of high
      resolution radiological techniques [computed tomography (CT), magnetic resonance
      imaging (MRI)] a high frequency (4-10%) of adrenal incidentalomas has been
      detected in the general population. It is still debated whether undiagnosed 21
      hydroxylase (21-OH) deficiency, accounting for more than 90% of congenital
      adrenal hyperplasia (CAH) cases, predisposes for adrenal tumours. We therefore
      performed an analysis of the prevalence of 21-OH germline mutations in patients
      with non-functional adrenal incidentalomas. SUBJECTS AND METHODS: Fifty Austrian
      patients with non-functional adrenal adenomas detected by CT for unrelated
      reasons were screened by PCR-based sequencing for the most common point mutations
      and by Southern blot analysis for large gene deletion/conversion events of the 21
      OH gene. RESULTS: Heterozygosity for large gene conversions was shown in 5 (10%),
      for Q318 point mutations in 2 (4%) and for the Intron2splice mutation in 1 (2%)
      of the 50 patients with adrenal adenomas. One (2%) patient (70 years of age),
      identified to have a chimeric CYP21AB gene with a junction site before Intron 2
      on one and a large (30 kb) deletion on the other allele, was diagnosed to be
      affected by CAH. CONCLUSION: 21-OH mutation screening indicates a higher
      frequency of classic CAH carriers (16%) and of manifest CAH (2%) due to 21-OH
      deficiency among patients with adrenal adenomas than in the general population (1
      2% carrier frequency for classic CAH).

PMID- 12072054
TI  - Pituitary tumours are multiclonal from the outset: evidence from a case with
      dural metastases.
AB  - In 1992 a 54-year-old man underwent transsphenoidal adenomectomy to remove a
      clinically nonfunctioning pituitary adenoma during which there was a transient
      cerebrospinal fluid (CSF) leak. He received radiotherapy to a small residual
      remnant. Follow-up magnetic resonance imaging (MRI) scan in 1997 showed an
      increase in the tumour in the pituitary stalk region and an additional intradural
      lesion at C1 level. In the absence of neurological symptoms and signs, an
      observational policy was followed. By 1999 the cervical dural lesion had enlarged
      and laminectomy was performed, during which three intradural lesions were
      removed. Histology and immunohistochemistry of the metastases were identical to
      those of the initial pituitary adenoma. Follow-up MRI scan showed extension of
      the pituitary remnant above the chiasma, requiring transfrontal surgery.
      Operation was complicated by secondary brain haemorrhage from which the patient
      died. Autopsy revealed a small amount of residual tumour at the top of the stalk
      and several small intradural tumour nodules at the level of the foramen magnum.
      Genetic analysis of the initial pituitary tumour identified significant allelic
      losses in keeping with its invasive nature, while that of the metastases
      indicated a separate clone as shown by retention of alleles lost in the primary
      tumour. The regrown pituitary tumour also appeared to be of a different clone to
      the initial tumour and the same as two of three of the first metastases (C1
      level). The foramen magnum metastasis showed the same loss of heterozygosity
      (LOH) pattern as one of the original C1 metastases and the pituitary tumour
      tissue obtained at autopsy. We speculate that at the initial pituitary surgery,
      cells seeded into the CSF and grew in the dura. These cells were from a different
      clone, implying that the original pituitary tumour contained at least two clones,
      possibly three, providing evidence for the contemporaneous oligoclonality of the
      original pituitary tumour.

PMID- 12072055
TI  - A new identified germline mutation of the RET proto-oncogene responsible for
      familial medullary thyroid carcinoma in co-existence with a hyperfunctioning
      autonomous nodule.

PMID- 12072058
TI  - Sunscreens and immune protection.

PMID- 12072059
TI  - HID and KID syndromes are associated with the same connexin 26 mutation.
AB  - BACKGROUND: Keratitis-ichthyosis-deafness (KID) syndrome is a debilitating
      ectodermal dysplasia that predisposes patients to develop squamous cell
      carcinomas in addition to leading to profound sensory deafness and
      erythrokeratoderma. We recently demonstrated that KID can be caused by a specific
      missense mutation in connexin 26 (GJB2). Another syndrome, called hystrix-like
      ichthyosis-deafnesss (HID) syndrome, strongly resembles the KID syndrome. These
      disorders are distinguished mainly on the basis of electron microscopic findings.
      We hypothesized that KID and HID syndromes may be genetically related. OBJECTIVE:
      To demonstrate by mutation analysis that HID and KID syndromes are genetically
      indistinguishable. METHODS: DNA was extracted from paraffin-embedded tissue
      samples of the first HID syndrome patient described in the literature. Since the
      KID syndrome mutation abolishes an AspI restriction site, we were able to screen
      the patient's DNA by polymerase chain reaction and subsequent restriction enzyme
      analysis. RESULTS: Restriction analysis of the connexin 26 gene in HID syndrome
      demonstrated the presence of the KID syndrome mutation that we previously
      described. This result was confirmed by direct DNA sequencing. CONCLUSIONS: We
      show that KID and HID syndromes are identical at the molecular level and confirm
      the clinical impression that these syndromes are one and the same. That previous
      clinical reports made a distinction may be a consequence of sampling artefacts;
      alternatively, genetic background effects such as the presence of concurrent
      mutations in other skin-expressed genes may modify the phenotype.

PMID- 12072060
TI  - Invasion of human keratinocytes by Staphylococcus aureus and intracellular
      bacterial persistence represent haemolysin-independent virulence mechanisms that
      are followed by features of necrotic and apoptotic keratinocyte cell death.
AB  - BACKGROUND: Colonization of human skin by Staphylococcus aureus is a
      characteristic feature of several inflammatory skin diseases, which is often
      followed by tissue invasion and severe cell damage. A crucial role has been
      attributed to staphylococcal haemolysins in the cytotoxicity to epidermal
      structures. OBJECTIVES: To investigate haemolysin-independent virulence to human
      keratinocytes. METHODS: The stable alpha-haemolysin, beta-haemolysin double
      negative S. aureus mutant DU 5720 was compared with the fully virulent parent
      strain 8325-4 and with its isogenic fibronectin-binding protein A/B-negative
      variant DU 5883 in an invasion model. RESULTS: This assay showed dose-dependent
      internalization of all the strains investigated by human HaCaT keratinocytes,
      with reduced internalization of DU 5883. Transmission electron microscopy
      revealed adhesion of staphylococci to cellular pilus-like extrusions, followed by
      the embedding of the bacteria in cellular grooves. Following attachment to the
      keratinocytes the staphylococci were engulfed into vesicles within the cytoplasm
      where some bacteria persisted for 24-48 h. Addition of cytochalasin D strongly
      reduced the bacterial uptake, suggesting an active keratinocyte process.
      Bacterial invasion was followed by severe keratinocyte cell damage showing the
      morphological changes of cytotoxic and, to a lesser extent, apoptotic cell death
      as determined by the trypan blue exclusion test and the terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick end labelling assay. The
      highest levels of lethal cytotoxicity were observed in haemolysin-producing
      strains, whereas the induction of apoptosis seemed to depend on internalization.
      CONCLUSIONS: Staphylococcal invasion of human keratinocytes represents a potent
      staphylococcal virulence factor, which, independently of alpha- and beta
      haemolysins, leads to necrotic and apoptotic cell damage.

PMID- 12072061
TI  - Diagnosis and confirmation of epidermolytic palmoplantar keratoderma by the
      identification of mutations in keratin 9 using denaturing high-performance liquid
      chromatography.
AB  - BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is one of a number of
      disorders characterized by diffuse thickening of palm and sole skin. Although
      EPPK is not a life-threatening condition, palmoplantar keratoderma can be
      associated with cancer and heart disease and therefore differential diagnosis is
      important so that adequate surveillance can be provided for the more serious
      conditions. Most cases of EPPK are caused by mutations in the gene encoding the
      palm- and sole-specific keratin 9 (K9), and this provides an option for molecular
      diagnosis of this condition. OBJECTIVES: To identify the molecular basis of
      diffuse palmoplantar keratoderma in four British families. METHODS: Denaturing
      high-performance liquid chromatography (dHPLC) and DNA sequencing were used to
      screen exon 1 of the k9 gene for sequence variations. RESULTS: The dHPLC profiles
      obtained from individuals with EPPK differed from control samples, indicating
      sequence variations within the fragment analysed. The profiles varied between
      families, suggesting that underlying mutations were different for each family;
      this was confirmed by DNA sequencing. In three cases previously reported
      mutations were found that resulted in the change of methionine156 to valine and
      arginine162 to either tryptophan or glutamine. A novel mutation was identified in
      a fourth family that changed valine170 to methionine. dHPLC was used to screen
      control samples for this sequence variation and confirmed that it was not a
      common polymorphism. CONCLUSIONS: These results confirm the diagnosis of EPPK in
      these families and underline the usefulness of dHPLC as a method of screening
      samples for heterozygous mutations.

PMID- 12072062
TI  - Mutation analysis of the ATP2A2 gene in Taiwanese patients with Darier's disease.
AB  - BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder
      characterized by abnormal keratinization and acantholysis. Pathogenic mutations
      in the ATP2A2 gene encoding SERCA2, a calcium pump of the sarco/endoplasmic
      reticulum, have recently been identified. OBJECTIVES: To identify mutations of
      the ATP2A2 gene in Taiwanese patients with DD. METHODS: Mutation analysis of
      genomic DNA was performed on five families with DD and two sporadic cases. All 21
      exons and the flanking intron boundaries were amplified and followed by direct
      sequencing. Restriction fragment analysis or direct sequencing in each family and
      in normal controls further verified the mutations. RESULTS: Mutations in the
      functional domains of the ATP2A2 gene were identified and verified in all seven
      pedigrees. They consisted of four mis-sense mutations (R131Q, P680L, G703S,
      G807R), one altered splice-site mutation (2980 + 5insA) and one frameshift
      deletion mutation (1457-1458delAG). Of these, R131Q, which was reported twice
      previously, was detected in two unrelated families. The remaining five were novel
      mutations. CONCLUSIONS: Six pathogenic mutations in the ATP2A2 gene were
      identified in seven Taiwanese DD pedigrees. The results confirmed that most
      mutations in the ATP2A2 gene are private and of the mis-sense type.

PMID- 12072063
TI  - Liposomal tacrolimus lotion as a novel topical agent for treatment of immune
      mediated skin disorders: experimental studies in a murine model.
AB  - BACKGROUND: Systemic but not topical tacrolimus (TAC) is effective against
      psoriasis. Mechanical methods that enhance skin penetration by TAC increase its
      topical antipsoriatic effect. Liposomal delivery of TAC would increase its
      penetration of skin, allow for slow release and diminish its toxicity.
      OBJECTIVES: To test a liposomal TAC (LTAC) formulation in a murine model.
      METHODS: Drug penetration was assessed using radiolabelled LTAC, and the effect
      of TAC and LTAC on Balb/c skin graft survival and on ovalbumin-induced delayed
      type hypersensitivity reactions was tested in C57BL/6 mice. RESULTS: Radiotracer
      studies showed that topical application of LTAC achieved nine times the
      concentration of TAC at a target site than did systemic administration of TAC.
      Combination of systemic and topical LTAC significantly increased mean +/- SD skin
      graft survival (14.8 +/- 1.5 days) compared with systemic TAC (8.0 +/- 0.7 days)
      and control mice (8.4 +/- 1.2 days). LTAC was more effective systemically than
      TAC in the prevention of delayed-type hypersensitivity reactions. Topical LTAC
      also prevented this response. CONCLUSIONS: Topical LTAC was effective in this
      model of immune-mediated skin disease. Because LTAC achieves higher skin
      concentrations than systemic TAC it may be an effective delivery system for TAC
      in the treatment of psoriasis.

PMID- 12072064
TI  - Formation of cornified cell envelope in human hair follicle development.
AB  - BACKGROUND: Cornified cell envelope (CCE) formation is an important step in the
      final stage of keratinization, in which CCE precursor proteins including
      involucrin and loricrin are cross-linked by keratinocyte transglutaminases
      (TGases) to the inner surface of the plasma membrane of cornified cells, while
      the outer surface is coated with material derived from secreted lamellar
      granules. OBJECTIVES: Skin samples from human fetuses of a series of estimated
      gestational age (EGA) (49-163 days) were studied for the prescence of precursor
      proteins. Methods TGase activity was studied by in situ TGase activity assay, and
      ultrastructural features of CCE formation were observed at each stage of hair
      follicle development. We used immunofluorescent labelling to investigate the time
      and site of expression of CCE precursor proteins involucrin and loricrin, TGases
      1, 2 and 3, and a 25-kDa lamellar granule-associated protein (LGP) in developing
      human hair follicles. RESULTS: In the hair germ (65-84 days EGA) (corresponding
      to the stages 1-2 of murine hair follicle morphogenesis), only TGase 2 was
      observed in the entire hair germ, where in situ TGase activity was weakly
      positive, although thickening of cell membrane was not seen ultrastructurally. In
      the hair peg (85-104 days EGA) (corresponding to the stage 3 of murine hair
      follicle morphogenesis), loricrin and TGase 2 were seen in cells of the upper
      part of the hair peg while TGase 1, 3 and LGP were observed in the inner cells of
      the hair peg. In situ TGase activity was weakly positive in the upper part and
      inner cells of the hair peg. In the bulbous hair peg (105-135 days EGA)
      (corresponding to the stages 4-6 of murine hair follicle morphogenesis) and
      differentiated lanugo hair follicle (> 135 days EGA) (corresponding to the stages
      7-8 of murine hair follicle morphogenesis), immunoreactivities of involucrin,
      loricrin, TGase 1, 2, 3, in situ TGase activity and LGP were detected in the
      inner root sheath cells, hair canals and inner cells of the outer root sheath in
      the region of the isthmus. Ultrastructurally, thickening of cell membrane was
      already seen in the inner root sheath cells of the bulbous hair peg and electron
      dense, thick CCE was observed in the hair cuticle and hair canal of
      differentiated lanugo hair follicle. CONCLUSIONS: These data indicate that, in
      terms of CCE formation, certain portions of the developing human hair follicle
      have already been determined in differentiation of the hair canal and cuticle at
      the hair peg stage.

PMID- 12072065
TI  - Biochemical and histochemical changes pertaining to active and healed cutaneous
      tuberculosis.
AB  - BACKGROUND: Fibrosis is one of the major causes of post-treatment morbidity in
      tuberculosis. The molecular basis of fibrosis in active and healed tuberculous
      lesions is yet to be fully characterized. OBJECTIVES: To measure the tissue
      levels of collagen, elastin, fibronectin, transforming growth factor-beta (TGF
      beta) and zinc in active and healed lesions of cutaneous tuberculosis. PATIENTS
      AND METHODS: Biopsy lesions obtained from 17 patients with active cutaneous
      tuberculosis and 12 patients after a 6-month regimen of antituberculous
      chemotherapy were examined. Collagen, elastin and zinc were estimated
      biochemically. In addition, the presence of collagen IV, TGF-beta and fibronectin
      were determined immunohistochemically. RESULTS: It was found that collagen,
      elastin, fibronectin and TGF-beta levels were higher in the active lesions. The
      levels of zinc were similar in both active and healed lesions. Clinically, scar
      tissue or keloid formation was not seen in any of the healed lesions.
      CONCLUSIONS: Effective antituberculous chemotherapy will lead to a substantial
      reduction of fibrosis and the consequent disability that can arise in patients
      with tuberculosis.

PMID- 12072066
TI  - Topical corticosteroid therapy for acute radiation dermatitis: a prospective,
      randomized, double-blind study.
AB  - BACKGROUND: Radiation dermatitis is a common side-effect of radiation therapy,
      but there is no current consensus about its appropriate therapy. OBJECTIVES: To
      compare treatment with topical 0.1% methylprednisolone vs. 0.5% dexpanthenol in a
      cohort of patients undergoing fractionated radiation therapy for breast cancer.
      METHODS: In a randomized, double-blind design, treatment was initiated at the
      beginning of radiation therapy and continued for 2 weeks after termination of
      radiation. Outcomes were compared by three different measures: clinical (symptom
      score), functional (transepidermal water loss, TEWL) and subjective (quality of
      life, QOL). RESULTS: In a preliminary cohort of untreated patients undergoing
      radiation therapy, clinical signs and TEWL levels increased progressively during
      radiation therapy, reaching highest values at 5 and 4 weeks, respectively.
      Although neither topical treatment reduced the incidence of radiation dermatitis,
      both delayed the emergence of greatest clinical and TEWL scores until
      approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical
      symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general
      QOL improved after completion of radiation therapy, skin-related QOL declined.
      However, the skin-related QOL decline could be at least in part reversed by use
      of topical corticosteroid vs. dexpanthenol-containing emollient. CONCLUSIONS: We
      provide evidence that prophylactic and ongoing use of topical therapy with either
      topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but
      does not prevent radiation dermatitis. Our data suggest, but do not prove, a
      benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient.
      Further controlled studies with larger cohorts will be needed to determine
      optimal forms of topical therapy for radiation dermatitis.

PMID- 12072067
TI  - Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic
      alopecia: a controlled, 12-month randomized trial.
AB  - BACKGROUND: Hormone studies have demonstrated the androgen-dependent character of
      female androgenetic alopecia, but there have been few controlled studies of
      therapies for alopecia in women. OBJECTIVES: To compare topical minoxidil 2% and
      cyproterone acetate in the treatment of female alopecia. METHODS: Sixty-six women
      with female-pattern alopecia were randomly assigned for 12 cycles into two
      groups, 33 received two local applications (2 mL day-1) of topical minoxidil 2%
      plus combined oral contraceptive and 33 received cyproterone acetate 52 mg day-1
      plus ethinyl oestradiol 35 microg for 20 of every 28 days. RESULTS: A mean
      reduction of 2.4 +/- 6.2 per 0.36 cm2 in hairs of diameter > 40 microm was
      observed in the cyproterone acetate group (P = 0.05) and a mean increase of 6.5
      +/- 9 per 0.36 cm2 in the minoxidil group (P < 0.001). Comparison of the total
      number of hairs at 12 months and the body mass index (BMI) revealed a borderline
      positive correlation in the cyproterone acetate group (r = 0.39, P = 0.06) and a
      negative correlation in the minoxidil group (r = -0.42, P < 0.05). No significant
      difference was observed in the total number of hairs among cyproterone acetate
      patients according to the presence or absence of other symptoms of
      hyperandrogenism, whereas in the minoxidil group, the total number of new hairs
      was higher in patients with isolated alopecia (Delta = 8.1; P < 0.05). Variations
      in scalp seborrhoea were significant in both groups, but the result was better
      (for acne and hirsutism as well) in the cyproterone acetate group than in the
      minoxidil group (P < 0.001). CONCLUSIONS: Minoxidil treatment was more effective
      in the absence of other signs of hyperandrogenism, hyperseborrhoea, and menstrual
      cycle modifications when the BMI was low, and when nothing argued in favour of
      biochemical hyperandrogenism. Cyproterone acetate treatment was more effective
      when other signs were present and when the BMI was elevated, factors that
      favoured a diagnosis of biochemical hyperandrogenism.

PMID- 12072068
TI  - Photodynamic therapy for the treatment of extramammary Paget's disease.
AB  - BACKGROUND: Surgical and ablative treatment modalities for extramammary Paget's
      disease (EMPD) have high recurrence rates and can be associated with significant
      morbidity. OBJECTIVES: To evaluate photodynamic therapy (PDT) for the treatment
      of EMPD. METHODS: We conducted a retrospective review of notes and histology of
      five men with anogenital, groin and axillary EMPD treated with PDT at Roswell
      Park Cancer Institute between 20 April 1995 and 1 February 2001. RESULTS: Sixteen
      EMPD lesions were treated with topical aminolaevulinic acid (ALA)-PDT. Eleven of
      these lesions had failed previous Mohs micrographic surgery, excision or laser
      ablation. When evaluated 6 months after one treatment with ALA-PDT, eight of 16
      (50%) sites achieved a complete clinical response (CR); six of eight CRs were in
      lesions that had failed prior conventional therapies. Three of the eight CRs
      (37.5%) recurred at 9, 10 and 10 months. One patient who was partially responsive
      to topical ALA-PDT subsequently received systemic Photofrin(R)-PDT, with a
      complete clinical and histological response at 1 year. Functional and cosmetic
      outcome was excellent in all patients. CONCLUSIONS: PDT is an effective treatment
      for EMPD. Recurrence rates are high with topical ALA-PDT, but comparable with
      standard therapies. Topical ALA-PDT causes little scarring and is preferred for
      superficial disease and mucosal surfaces. Systemic Photofrin(R)-PDT may be better
      suited for bulky disease. While further studies are indicated, PDT is well
      tolerated and appears to be a useful therapy for EMPD.

PMID- 12072070
TI  - Diet and basal cell skin cancer: results from the EPIC-Norfolk cohort.
AB  - BACKGROUND: The incidence of non-melanoma skin cancer (NMSC) in Britain has been
      increasing over the past 50 years. This has been attributed to increased sunlight
      exposure, but the increased exposure has not been quantified, and in any case,
      much of the increase in incidence has occurred in those parts of the body, mainly
      the head and neck, that have always been exposed to sunlight. There is evidence
      that increased dietary fat intake has increased the sensitivity of the skin to
      the carcinogenic potential of sunlight, particularly in causing squamous cell
      tumours. OBJECTIVES: To test the hypothesis that increased dietary fat is a risk
      factor for NMSC. METHODS: The hypothesis was tested in a nested case-control
      study. The cohort was that recruited for the EPIC-Norfolk study, the cases (n =
      123) were subjects with NMSC diagnosed since recruitment, and the controls (n =
      247) were randomly selected from the same cohort. The effect of diet on the
      incidence of NMSC was assessed using conditional logistic regression. RESULTS: As
      there were so few cases (14) with squamous cell tumours they were excluded from
      the statistical analyses. Fat intake was not found to be a risk factor: the
      unadjusted odds ratio (OR) of basal cell cases vs. controls was estimated as
      0.860/(25.5 g total fat daily) with 95% confidence interval (CI) (0.663, 1.116),
      P = 0.25. Exploratory analyses of diet components and food groups found a
      protective effect of increased vitamin E consumption: unadjusted OR of basal cell
      cases vs. controls was 0.731/(3.06 mg vitamin E daily), 95% CI (0.564, 0.948), P
      = 0.015. Adjusted analyses gave broadly similar results. CONCLUSIONS: The
      potentiating factor remains unknown: if dietary fat has any effect on NMSC, it is
      not apparent when basal cell tumours are considered. There was no evidence of a
      generalized healthy eating effect. A substantial protective effect was found in
      exploratory analyses for the fat soluble antioxidant vitamin E.

PMID- 12072069
TI  - Quality of life in 6497 Nordic patients with psoriasis.
AB  - BACKGROUND: Disease-specific psoriasis-related quality of life (QOL) measures
      have recently been developed and used in several hospital-based investigations.
      However, little is known about the impact of psoriasis on QOL in people with
      psoriasis who are not referred by dermatologists. OBJECTIVES: The purpose of the
      study was to investigate psoriasis-related QOL in a large sample of members of
      the psoriasis associations from the Nordic countries, and to compare the results
      with those from psoriasis patients recruited from Nordic dermatologists or Nordic
      University clinics. PATIENTS AND METHODS: A total of 5795 association members and
      702 patients rated their psoriasis severity and completed the Psoriasis
      Disability Index and the Psoriasis Life Stress Index. RESULTS: Patients reported
      greater disease severity and greater impairment of QOL than members of
      associations, and Norwegian participants reported greater disease severity and
      greater impairment of QOL than participants from the remaining Nordic countries.
      Older and married participants reported less impairment of QOL than younger
      participants and those living alone. When controlling for the influence of these
      and other demographic and socio-economic factors, self-reported severity emerged
      as the most significant predictor of psoriasis-related QOL, explaining 32-26% of
      the variation in QOL scores, with the remaining factors only accounting for 4-5%
      of the variation. Although correlated with self-reported severity, Psoriasis Area
      and Severity Index scores were not a significant predictor of QOL in the patient
      sample. CONCLUSIONS: Though self-reported severity may be the most important
      predictor, further research is needed to determine factors explaining the
      remaining variance in psoriasis-related QOL.

PMID- 12072071
TI  - A new computerized methodology to analyse tumour site in relation to phenotypic
      traits and epidemiological characteristics of cutaneous malignant melanoma.
AB  - BACKGROUND: While sunlight is important in the aetiology of cutaneous malignant
      melanoma (CMM), the relationship between skin areas receiving intermittent or
      chronic sun exposure and the development of CMM has not been fully explored.
      There is a requirement for an improved method for more detailed site mapping and
      for analysis of tumour density in different areas of the skin in relation to the
      type of sun exposure, phenotypic traits and prognosis of patients with CMM.
      OBJECTIVES: To describe and demonstrate the use of EssDoll, a new computerized
      method to map and analyse tumour sites. METHODS: We have used the new software to
      analyse data on 2517 patients with 2608 primary CMMs. RESULTS: The results
      obtained were consistent with previous data on the distribution of CMM in men and
      women. The distribution of CMM on the back was uneven, with the density on the
      upper back being twice that on the lower back. CONCLUSIONS: The new methodology
      allows a more accurate mapping and analysis of skin tumour site, including
      determination of tumour density. This improves the possibility of analysing
      tumour site in relation to aetiological, phenotypic and prognostic parameters.

PMID- 12072073
TI  - Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan
      women but not men: results of a 2-year surveillance study.
AB  - BACKGROUND: The reported frequency of recovery of fungi from infected nails
      varies according to the geographical area. OBJECTIVES: To establish the nature of
      the causal agents in a sample of the Libyan population presenting with suspected
      onychomycosis. METHODS: Samples were taken from the infected fingernails of 648
      patients attending the Tripoli Medical Centre. RESULTS: Samples from 500 patients
      proved positive for fungi following culturing, while 476 were potassium hydroxide
      and culture positive. Of the culture-positive samples, yeasts of the genus
      Candida (C. albicans, C. parapsilosis, C. glabrata, C. guillermondii and C.
      tropicalis) were the dominant cause of this condition in women (417 of 434, 96%)
      but were responsible for only a minority of cases in men (three of 66, 5%). In
      contrast, dermatophytes (Trichophyton violaceum, T. rubrum, T. mentagrophytes and
      Microsporum canis) were responsible for this condition in the majority of cases
      in men (53 of 66, 80%) but only 3% (15 of 434) of cases in women. The mould
      Aspergillus nidulans was isolated from the nails of 10 (15%) men and two (0.5%)
      women. CONCLUSIONS: The data obtained in this study reveal an almost total
      separation of the aetiological agents responsible for onychomycosis based on
      gender.

PMID- 12072072
TI  - Psychological factors associated with hand dermatoses: which subgroup needs
      additional psychological care?
AB  - BACKGROUND: The aetiology of hand dermatoses (HD) is very heterogeneous.
      Psychological influences on severity and coping in hand eczema have been only
      rarely investigated. OBJECTIVES: To investigate whether psychological factors
      correlate with somatic factors, in order to be able to estimate the possible need
      for psychosocial treatment of these patients. METHODS: In a cross-sectional study
      101 hand dermatosis patients (49F, 52M) with psoriasis (n = 26), vesicular hand
      eczema (n = 33) or contact dermatitis (n = 42) were examined with regard to
      dermatological [diagnosis, severity, Erlanger Atopy Score (EAS)], allergic (patch
      test) and psychological aspects [Coping with Chronic Skin Diseases questionnaire
      (CSD), Allover Depression Scale (ADS), Social Readjustment Rating Scale (SRRS),
      questionnaire for measuring Factors of Aggression (FAF)],and Visual Analogue
      Scales (VAS) concerning itching, scratching and impairment. Subgroups of high
      stress responders (high-SR) vs. low stress responders (low-SR) were also
      examined. RESULTS: Of the patients with HD, 47.52% are convinced that 'stress'
      influences the course of their disease. Analysis of variance shows that the
      subjective reaction to stress (high-SR) correlates with higher severity scores,
      more itching, higher depression scores and more life events. High-SRs were
      younger and the onset of the disease was earlier compared with patients without a
      subjective reaction to stress (low-SR). In the CSD those with especially high-SR
      but negative patch-test results stated significantly higher values for itching,
      helplessness and search for information. CONCLUSIONS: Psychological factors
      should be taken into consideration in the treatment of patients with HD. High-SR
      patients with a negative patch-test seem to require more adjuvant psychological
      care.

PMID- 12072074
TI  - A retrospective study of 150 patients with lentigo maligna and lentigo maligna
      melanoma and the efficacy of radiotherapy using Grenz or soft X-rays.
AB  - BACKGROUND: Lentigo maligna (LM) and lentigo maligna melanoma (LMM) are the most
      common melanocytic neoplasms on sun-exposed skin of elderly patients. OBJECTIVES:
      To perform a retrospective study of 150 patients with LM and LMM treated with
      radiotherapy using Grenz or soft X-rays. METHODS: The information recorded and
      analysed included gender, age, diagnosis, size of the lesion, localization, X-ray
      treatment, recurrence rate, other skin malignancies and non-dermatological
      neoplasms. RESULTS: The 150 patients comprised 78 women and 72 men (mean age 70
      years). Ninety-three patients had LM, 54 had LMM and three had both neoplasms.
      Ninety per cent of lesions were located on the face. Treatment was with Grenz
      rays in 96 patients with LM and 11 with LMM (70%) and with soft X-rays in 46
      patients with LMM (30%). Three patients were treated using both modalities. One
      hundred and one patients were followed up for at least 2 years after radiotherapy
      (mean 8 years). The mean time to recurrence was 45.6 months, and the recurrence
      rate was 7% (seven of 101). Other skin malignancies were observed in 65 of 150
      patients, including basal cell carcinoma in 23 (35%) and actinic keratosis in 20
      (31%). Four patients developed internal cancers. CONCLUSIONS: The study showed
      that radiotherapy of LM and LMM was curative. In particular, radiotherapy proved
      to be an excellent treatment for elderly patients. Owing to the high incidence of
      other skin cancers, LM patients need careful follow-up.

PMID- 12072076
TI  - Differences of skin irritation between Japanese and European women.
AB  - BACKGROUND: After using cosmetics, Japanese women frequently complain about
      sensitive, stinging skin. We wondered whether Japanese women's skin is more
      sensitive than that of Caucasians. OBJECTIVES: To examine possible racial
      differences of skin irritation and subjective sensations. METHODS: We performed
      patch testing on the forearm with sodium lauryl sulphate (SLS) at different
      concentrations (0.25%, 0.5%) and 24-h exposure time. Skin reaction was evaluated
      by measurement of transepidermal water loss (TEWL), stratum corneum hydration,
      sebum secretion, laser Doppler flowmetry (LD), content of melanin and erythema.
      During a stinging test with 10% lactic acid (applied to one side of the cheeks)
      the subjects were asked to describe the present intensity of any sensation. We
      used a Chromameter to measure skin colour before and after application of lactic
      acid. This study was performed in Marburg, Germany, with healthy Japanese and
      German women living in Marburg. RESULTS: After SLS testing, we found no
      significant differences of the barrier function in the stratum corneum, but we
      found significant subjective sensory differences between Japanese and German
      women. CONCLUSIONS: Japanese women may complain about stronger sensations
      reflecting a different cultural behaviour rather than measurable differences in
      skin physiology; however, a faster penetration of SLS in Japanese cannot be
      excluded.

PMID- 12072075
TI  - Comparative frequency of patch test reactions to topical antibiotics.
AB  - BACKGROUND: Neomycin, clioquinol and fusidic acid are all topical antibiotics
      widely used in dermatological practice in the U.K., either as a single agent or
      in combination with topical corticosteroids. However, an adverse effect of
      topical antibiotics is contact sensitization. OBJECTIVES: To examine the
      frequency of positive patch test reactions to fusidic acid, clioquinol and
      neomycin. METHODS: To compare the frequency of allergic patch test reactions over
      1 year, we patch tested all patients attending the St John's Institute of
      Dermatology contact dermatitis clinic for one calendar year with fusidic acid,
      neomycin and clioquinol. RESULTS: We patch tested 1119 patients. Positive patch
      test reactions to neomycin were noted in 40 patients (3.6%), compared with eight
      patients (0.7%) to clioquinol and three patients (0.3%) to fusidic acid. The
      frequency of medicament allergy to neomycin was thus five times more common than
      to clioquinol and ten times more common than to fusidic acid. Although fusidic
      acid is not part of our extended standard series, it is in our medicaments
      series. Therefore, in the second part of our study, we reviewed all cases of
      positive patch test reactions to fusidic acid over the last 20 years. We found
      that the frequency of hypersensitivity has decreased since the early 1980s
      despite increasing usage; the current average frequency being 1.62 patch-tested
      patients per year (1.45%) of those patch tested to the medicaments series). The
      most common diagnosis in such patients was stasis dermatitis (54.2%).
      CONCLUSIONS: The frequency of fusidic acid allergy in an eczema population is low
      and is comparable with published data from over 10 years ago.

PMID- 12072078
TI  - Generalized pustular and erythrodermic psoriasis associated with bupropion
      treatment.
AB  - Severe drug eruptions may cause diagnostic and therapeutic difficulty when they
      mimic or provoke endogenous patterns of dermatosis. We report three patients with
      known psoriasis in whom use of bupropion (Zyban), prescribed to assist with
      cessation of smoking, led to severe pustular or erythrodermic exacerbation of
      psoriasis within 3-5 weeks. All patients were systemically unwell and required
      hospitalization to control the disease flare.

PMID- 12072077
TI  - Reliability testing of the Six Area, Six Sign Atopic Dermatitis severity score.
AB  - BACKGROUND: The Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score is
      an objective atopic eczema severity index designed principally to assess response
      to treatment in therapeutic trials. Validity has been demonstrated in single and
      multicentre clinical trials, although data on the reliability of the index have
      not previously been published. OBJECTIVES: To assess inter- and intraobserver
      variability of the SASSAD index. METHODS: Six observers with experience in the
      assessment of atopic eczema were each asked to score disease severity in six
      patients with moderate to severe atopic eczema using the SASSAD index. Repeat
      observations were carried out on randomly selected patients by each observer to
      estimate intraobserver variation. RESULTS: The interobserver variation in total
      SASSAD scores for each patient ranged from 7 to 30 (median 15.5) out of a maximum
      possible score of 108. The intraclass correlation coefficient ri for the total
      scores among all six observers was quite high at 0.70, although interobserver
      agreement for individual components of the index was poor to moderate. The
      maximum recorded intraobserver variation in total SASSAD score in any of the
      examined patients was 8 units. CONCLUSIONS: As with many other tested atopic
      eczema scoring indices, the SASSAD index is subject to significant interobserver
      variation, reflecting the difficulties in reliably assessing eczema severity
      objectively.

PMID- 12072079
TI  - Systemic itraconazole in the yellow nail syndrome.
AB  - Although a number of treatments have been reported to be effective with yellow
      nail syndrome (YNS), vitamin E at high doses is the only one that has been
      successfully utilized in a consistent number of patients affected by YNS. Recent
      data indicate that itraconazole pulse regimen may be effective in this disease.
      We report our experience with itraconazole treatment in patients affected by YNS.
      Systemic itraconazole was administered in eight patients (five males and three
      females; mean age 55.2 years), at a dosage of 400 mg daily for 1 week a month for
      6 months. Nail growth was measured every 3 months. Complete cure was achieved in
      two of eight patients, with mild improvement in two and no improvement in four.
      The results of our study show that itraconazole cannot be considered effective
      for YNS, especially if compared with vitamin E, the efficacy and tolerability of
      which is already proven.

PMID- 12072080
TI  - Multiple basaloid follicular hamartomas associated with acrochordons, seborrhoeic
      keratoses and chondrosarcoma.
AB  - Basaloid follicular hamartoma is an uncommon neoplasm with distinctive
      histopathological findings. It presents as four distinctive clinical forms: a
      solitary papule, a localized plaque of alopecia, a localized linear and
      unilateral type, and generalized papules with associated alopecia and myasthenia
      gravis. Histologically, basaloid follicular hamartomas are characterized by thin
      branching strands and thick cords of basaloid or squamoid cells extending from a
      follicle into a loose, fibrillar, fibrocytic or mucinous connective tissue
      stroma. We report a case of long-standing, generalized basaloid follicular
      hamartomas associated with acrochordons, seborrhoeic keratoses, and a history of
      chondrosarcoma. In general, solitary tumours are sporadic; multiple tumours are
      inherited and frequently associated with a syndrome. Further surveillance is
      warranted to determine if the association of multiple basaloid follicular
      hamartomas and chondrosarcoma constitutes an inherited syndrome.

PMID- 12072081
TI  - Brittle nails and dyspareunia as first clues to recurrences of malignant
      glucagonoma.
AB  - Glucagonoma syndrome is a paraneoplastic syndrome in which the occurrence and
      resolution of the characteristic necrolytic migratory erythema lesions parallel
      the course of the underlying glucagonoma. Nail abnormalities and dyspareunia are
      rarely reported in this syndrome. We describe a case of glucagonoma syndrome in
      which recurrent brittle nails and dyspareunia gave the patient the first clues of
      the recurrence of glucagonoma. It is possible that the significance of
      onychoschizia and dyspareunia has been overlooked in glucagonoma syndrome because
      patients might not report these problems to their doctors. Our case illustrates
      the importance of examining the nail and genital mucosa in patients with
      glucagonoma syndrome and including this syndrome in the differential diagnosis of
      onychoschizia and dyspareunia.

PMID- 12072082
TI  - Progressive extensive osteoma cutis associated with dysmorphic features: a new
      syndrome? Case report and review of the literature.
AB  - Osteoma cutis, also called cutaneous ossification, refers to the rare occurrence
      of bone in the skin. It may be primary, occurring in normal skin, or secondary,
      occurring in disrupted skin tissue. A 42-year-old white woman presented with long
      standing progressive primary osteoma cutis involving her head and neck, trunk and
      extremities. She had craniofacial dysmorphism with mid-face hypoplasia, including
      saddle nose deformity, mild to moderate generalized joint hypermobility,
      extensive paravertebral ossification, and disc space calcification. The
      differential diagnosis for this entity is presented. This phenotype may be a
      previously undescribed syndrome.

PMID- 12072083
TI  - Generalized lichen nitidus successfully treated with an antituberculous agent.
AB  - We describe a Japanese girl with generalized lichen nitidus. She had been exposed
      to Mycobacterium tuberculosis at 6 years of age via her teacher. At 8 years of
      age, she developed severe contact dermatitis on sun-exposed areas after contact
      with Japanese lacquer trees. Shortly after, numerous tiny, shiny, flesh-coloured
      papules developed over the upper part of her body. At 10 years of age, she was
      exposed to a school outbreak of M. tuberculosis. Her eruption showed no response
      to topical corticosteroids or oral tranilast, but most of the papules completely
      disappeared after she had received oral isoniazid for 6 months.

PMID- 12072084
TI  - A case of linear scleroderma with muscle calcification.
AB  - We report a 21-year-old man with linear scleroderma with muscle calcification
      revealed by a computed tomographic (CT) scan. Levels of serum calcium and
      phosphorus were normal. This is the first report of localized scleroderma with
      muscle calcification. Muscle involvement may cause contracture or functional
      abnormalities of the extremities. Therefore, CT scans may be useful in evaluating
      muscle involvement in patients with localized scleroderma.

PMID- 12072085
TI  - Lymphocytic infiltrates as a presenting feature of Sweet's syndrome with
      myelodysplasia and response to cyclophosphamide.
AB  - Sweet's syndrome has a well-recognized association with malignancies, around half
      of which have been acute myelogenous leukaemia. There are also numerous reports
      of Sweet's syndrome in association with myelodysplasia. We report two patients
      with Sweet's syndrome in whom the classical histological appearances were
      preceded by dermal lymphocytic infiltrates. A literature search using PubMed
      indicates that this phenomenon has not been previously reported. The cases
      demonstrate the chronicity of Sweet's lesions in association with haematological
      disease and the need for repeat biopsies to make the diagnosis. We also describe
      successful treatment with cyclophosphamide, which adds to the list of second-line
      drugs that may be used in Sweet's syndrome.

PMID- 12072086
TI  - CD30-positive cutaneous T-cell lymphoma with concurrent solid tumour.
AB  - Extranodal CD30+ T-cell lymphomas seldom carry classical t(2;5) translocation and
      are usually anaplastic large cell lymphoma kinase protein negative. They cover a
      wide spectrum of histological and clinical behaviour. The prognosis of CD30+
      cutaneous T-cell lymphoma (CTCL) is good in the absence of nodal primary or
      disseminated disease. These lesions can undergo spontaneous regression, and
      overlap with the group of lesions of lymphomatoid papulosis. Although an
      increased incidence of solid tumours has been reported in patients with CD30+ non
      Hodgkin lymphoma of the skin, reports of concurrent malignancies are rare in
      CD30+ CTCL. We report two patients with CD30+ CTCL who, respectively, had
      concurrent disseminated gastric carcinoma and bilateral ovarian teratoma. Despite
      an aggressive clinical and histological appearance, both cases ran favourable
      clinical courses. The CTCL responded completely to chemotherapy in one patient,
      who eventually succumbed to gastric cancer. In the other patient, lesions
      regressed spontaneously after bilateral oophorectomy. A possible relationship
      between the lymphoma and the solid tumours is discussed.

PMID- 12072087
TI  - T-zone lymphoma with cutaneous involvement: a case report and review of the
      literature.
AB  - T-zone lymphoma (TZL) is a rare subtype of nodal peripheral T-cell lymphoma
      characterized by a clonal expansion of T-zone lymphocytes accompanied by a
      proliferation of other T-zone constituents. Non-specific cutaneous alterations
      are seen in about one-third of all cases, but specific cutaneous involvement is
      extremely rare. We present a case of TZL with secondary skin infiltration, review
      the literature on cutaneous manifestations of TZL and discuss the differential
      diagnosis of TZL.

PMID- 12072088
TI  - Citric acid treatment of non-healing ulcers in leprosy patients.

PMID- 12072089
TI  - Mycosis fungoides mimicking granuloma annulare.

PMID- 12072090
TI  - Loss of beta-catenin expression is associated with disease progression in
      malignant melanoma.

PMID- 12072091
TI  - Anti-laminin 5 pemphigoid and acquired haemophilia.

PMID- 12072092
TI  - Unilateral Darier's disease complicated by Kaposi's varicelliform eruption
      limited to the affected skin.

PMID- 12072093
TI  - Cholesterol embolism: an often unrecognized cause of leg ulcers.

PMID- 12072094
TI  - Familial mycosis fungoides.

PMID- 12072095
TI  - Liquid nitrogen cryotherapy of common warts: cryo-spray vs. cotton wool bud.

PMID- 12072097
TI  - Absence of t(14,18) chromosomal translocation in primary cutaneous B-cell
      lymphoma.

PMID- 12072099
TI  - Thalidomide and sexual dysfunction in men.

PMID- 12072100
TI  - Hypersensitivity to non-steroidal anti-inflammatory drugs and chronic urticaria
      cured by treatment of Blastocystis hominis infection.

PMID- 12072103
TI  - Perfusion reborn.

PMID- 12072104
TI  - Levamisole treatment enhances protective antibody response to hepatitis B
      vaccination in hemodialysis patients.
AB  - Hemodialysis shows a high risk for hepatitis B infection, and hepatitis B virus
      (HBV) vaccination has now become a routine procedure. Unfortunately, 40% to 50%
      of hemodialysis patients do not have adequate protective antibodies against the
      HBV vaccination which is thought to be due to depressed cell mediated immunity.
      Levamisole has been reported to stimulate depressed T-cell activity and enhance B
      lymphocyte function and restore delayed hypersensitivity reactions in immune
      depressed patients. We studied the effects of levamisole, an immunomodulatory
      agent, on the protective antibody response of hemodialysis patients to the HBV
      vaccination. Our hemodialysis patients with negative anti-HBs antibody routinely
      received 40 microg doses of recombinant HBV vaccine intramuscularly at 0, 1, and
      6 months, and we followed serum anti-HBs levels. Patients with a serum antibody
      level of >10 mIU/ml were considered as responders. Study groups were classified
      as follows. Group 1 was comprised of 96 chronic hemodialysis patients with
      negative anti-HBs and HBV core antibody (52 male, 44 female, mean age of 45 +/-
      15 years and mean hemodialysis duration of 46 +/- 40 months) who received HBV
      vaccination; 55 patients (57%) were found to be responders. Group 2 was comprised
      of 19 randomly selected patients who had never received hepatitis B vaccine (13
      male, 6 female, mean age of 42 +/- 14 years, mean duration of hemodialysis 31 +/-
      27 months) and who were started on an HBV vaccination protocol with levamisole
      per os 80 mg after each hemodialysis session for 4 months and followed up on
      serum anti-HBs levels. Seventeen of the patients completed this levamisole
      treatment. Fourteen of the 17 patients had the levels of the protective serum
      antibody indicating a higher response rate when compared with patients who did
      not receive levamisole (82% versus 57%, respectively, p < 0.05). Group 3 was
      comprised of 19 patients randomly selected from persons who did not respond to
      previous vaccination programs (10 male, 9 female, mean age of 51 +/- 14 years,
      mean duration of hemodialysis 41 +/- 31 months). A second HBV vaccination program
      was started with the same levamisole protocol. In this group, 18 patients
      completed this treatment model. Fourteen of them responded to the vaccination
      model. In Group 4, a second HBV vaccination program was applied without
      levamisole to 20 randomly selected persons who did not respond to the previous
      routine vaccination program (12 male, 8 female, mean age of 53 +/- 17 years, mean
      duration of dialysis 51 +/- 38 months). Only 3 of them responded to a second
      vaccination program. Comparing Group 3 with Group 4, there was a higher responder
      rate to HBV vaccination (77% versus 15%, respectively, p < 0.0001). These results
      show that levamisole treatment increases the response rate to the first HBV
      vaccination and of the previously unresponsive cases by modulating possible
      cellular immune response.

PMID- 12072105
TI  - A novel method for faster formation of rat liver cell spheroids.
AB  - Hepatocyte spheroids are expected to be the main component of the artificial
      liver bioreactor for their higher function. The preparation of hepatocyte
      spheroids, however, can require as many as 24 to 96 h. To reduce this time, we
      investigated a method employing a new technique of rat hepatocyte preparation and
      a dynamic culture. The modified Seglen's method for standard hepatocyte isolation
      was altered by elimination of ethyleneglycol bis(aminoethylether) tetraacetate
      from the first perfusate and calcium from the second perfusate. Isolated
      hepatocytes were cultured in a spinner flask by spinning at 120 rpm. The modified
      Seglen's method was used as a control. Cells obtained by the new method were more
      cohesive and formed a higher proportion of cell aggregates than control cells. In
      the spinning culture, hepatocytes had a tendency to aggregate and 80% of cells
      formed spheroids within 6 h of culturing. The mean size of spheroids was 68.5 +/-
      18.5 microm. Confocal laser scanning microscopy revealed that individual
      spheroids contained approximately 30% of nonparenchymal cells over their surface.
      Using the new hepatocyte preparation method followed by a spinning culture, we
      were able to produce hepatocyte spheroids in as few as 6 h.

PMID- 12072106
TI  - Comparison of coagulation activity tests in vitro for selected biomaterials.
AB  - Testing of coagulation induced by external communicating medical devices is an
      International Standardisation Organization (ISO) requirement for products exposed
      to human blood. Four categories of tests are indicated by ISO 10993/4: a clotting
      test (partial thromboplastin time; PTT), thrombin generation, fibrinogen
      deposition, or measurement of coagulation split products. We evaluated the
      specificity of these tests on various polymers and found only thrombin generation
      and fibrinogen binding sensitive and reproducible tests while thrombin generation
      correlated best with the classical PTT. The thrombin generation assay is
      therefore the method of choice for testing coagulation induced by biomaterials
      and medical devices.

PMID- 12072108
TI  - Laminin modified infection-preventing collagen membrane containing silver
      sulfadiazine-hyaluronan microparticles.
AB  - The newly developed laminin modified infection-preventing collagen membrane
      consists of a 3 component laminate, comprising 2 outer collagen layers and a
      central laminin layer. The 2 outer collagen layers (dense and porous layers) were
      fabricated by air-drying and freeze drying, respectively, and the laminin layer
      was formed by a straightforward liquid coating method. In addition, hyaluronan
      based microparticles containing silver sulfadiazine (AgSD) were incorporated into
      the 2 collagen layers (AgSD content 50 microg/cm2). Laminin coated collagen
      surfaces did not promote fibroblast attachment but showed a retarded fibroblast
      proliferation rate and an increased rate of collagen synthesis versus pure
      collagen surfaces. In an animal study, a laminin coating on a nonmedicated
      collagen membrane significantly increased both wound size reduction and vessel
      proliferation 7 days after application versus polyurethane film. Interestingly,
      the laminin coated AgSD medicated collagen membrane demonstrated higher wound
      size reduction and vessel proliferation and lower inflammation than the
      polyurethane control, suggesting that the laminin AgSD medicated collagen
      membrane substantially improves dermal wound healing.

PMID- 12072107
TI  - The effect of apo-transferrin on bacterial adhesion to biomaterials.
AB  - Apo-transferrin (apo-Tf), the iron deficient form of Tf, has been identified
      previously as a potent inhibitor of Staphylococcus epidermidis adhesion to
      polyurethane surfaces. In this study, the ability of apo-Tf to suppress the
      adhesion of two other strains of bacteria, namely a Gram-positive Staphylococcus
      aureus and a Gram-negative Pseudomonas aeruginosa to several biomaterials,
      including polystyrene, polymethylmethacrylate, and silicone, is documented. The
      presence of apo-Tf in the medium at 20 microg/ml lowered bacterial adhesion to
      all tested biomaterials more than fourfold. Moreover, apo-Tf exerted its
      inhibitory activity even when protein coated surfaces were used as substrates for
      bacterial adhesion. To emphasize the importance of apo-Tf in the prevention of
      bacterial adhesion, human serum was depleted of Tf, employing affinity
      chromatography, and was shown to lose its inhibitory activity toward bacterial
      adhesion. Upon addition of apo-Tf to Tf-depleted serum, the activity was
      reestablished, resulting in a marked reduction in the number of bacteria adhered
      to the surfaces. Following the enzymatic deglycosylation, apo-Tf retained its
      ability to prevent bacterial adhesion. These results indicate that the
      carbohydrate moiety does not seem to play a role in this activity. The presented
      data provide the evidence that the inhibitory activity of apo-Tf is not bacterial
      strain specific and that the presence of apo-Tf in the medium results in a
      significant reduction of bacterial adhesion to a variety of neat and/or protein
      coated surfaces.

PMID- 12072109
TI  - Chronic evaluation of the Cleveland Clinic CorAide left ventricular assist system
      in calves.
AB  - The Cleveland Clinic CorAide left ventricular assist system is based on a third
      generation, implantable, centrifugal pump in which a rotating assembly is
      suspended fully. To evaluate chronic in vivo system performance and
      biocompatibility, the CorAide blood pump was implanted in 18 calves for either 1
      month or 3 months. Hemodynamics were stable in all calves with a mean pump flow
      of 5.9 +/- 1.2 L/min and a mean systemic arterial pressure of 98 +/- 5 mm Hg.
      There were no incidences of bleeding, organ dysfunction, or mechanical failure in
      any of the 18 calves. Hemolysis occurred in only 1 calf due to outflow graft
      stenosis. Thrombus inside the pump, seen in 4 of the first 6 cases, was totally
      eliminated by a final redesign in the remaining cases, including the last 6
      implants conducted without anticoagulation therapy. The CorAide blood pump
      demonstrated good biocompatibility and reliable, effective system performance.

PMID- 12072110
TI  - A computational study of the effects of inlet guide vanes on the performance of a
      centrifugal blood pump.
AB  - This article presents computational studies on the effects of inlet guide vanes
      (IGVs) on the flow pattern and shear stress in a centrifugal blood pump. The
      effect of IGVs is to introduce a pre-swirl to fluid particles entering the
      impeller with the intention that the fluid particles will travel along the blade
      profile. Currently, most commercial centrifugal blood pumps employ straight
      radial impeller blades that are not hydrodynamically ideal for a good flow
      pattern within the blade passage. Flow separation and formation of vortices
      within the blade passage are believed to increase the degree of hemolysis and
      thrombosis. These are causes for blood clotting that will lead to malfunctioning
      of ventricular assist devices. Four IGVs of different geometrical profiles have
      been numerically investigated using a commercial software program CFX-Tascflow.
      The pump is operated at 2,000 rpm, and the results revealed that the relative
      flow patterns in the blade passage have been dramatically altered. The size of
      the vortices was reduced, and the pressure contours indicated a gradual rise from
      the impeller leading edge to the trailing edge. However, inclusion of IGV causes
      a drop in the pressure head generated. Higher frictional losses are incurred as
      fluid particles passed through the IGV. In addition, the IGV modifies the inlet
      velocity triangles, and this also contributes to a drop in the pressure head
      generated that is consistent with Euler's pump theory. The change in the flow
      patterns and the gradual variation of the pressure contours have led to lower
      shear stress within the blade passages as compared to the case without IGVs.

PMID- 12072111
TI  - Effects of ethylene oxide and steam sterilization on dialysis-induced cytokine
      release by cuprophan membrane.
AB  - The effects of sterilization modalities on dialysis-induced cytokine release are
      still unknown. To investigate these effects, 8 patients on chronic hemodialysis
      were enrolled for evaluating at different intervals interleukin-1beta (IL-1beta)
      and tumor necrosis factor-alpha (TNF-alpha) production (pg/ml/106). They were
      using a 1.3 m2 ethylene oxide (E3) or steam (E3S) sterilized Cuprophan membrane.
      The patients underwent a basal test with E3 (A1) and 2 following tests after 1
      (B1) and 2 (B2) months of E3S treatment, respectively. Finally, the last test was
      performed 1 month after the switch to E3 (A2). Il-1beta predialysis release by
      mononuclear cells was 162 +/- 114 pg/ml/106 in A1, 185 +/- 129 pg/ml/106 in B1,
      and 226 +/- 138 pg/ml/106 in B2, then decreased to 123 +/- 134 in A2 (p < 0.07).
      Il-1beta postdialysis levels were 234 +/- 238 pg/ml/106 in A1, 429 +/- 285
      pg/ml/106 (B1), and 438 +/- 473 pg/ml/106 (B2) with the steam membrane,
      decreasing to 204 +/- 134 pg/ml/106 in A2 (p < 0.01). TNF-alpha predialysis basal
      release (A1) was 826 +/- 817 pg/ml/106, 720 +/- 496 in B1, and 1079 +/- 515
      pg/ml/106 in B2, and finally 680 +/- 588 pg/ml/106 in A2 (p < 0.03). In
      postdialysis TNF-alpha levels were 963 +/- 542 pg/ml/106 in A1, 1,226 +/- 541
      pg/ml/106, and 1,183 +/- 776 in B1 and B2 respectively, and 388 +/- 297 pg/ml/106
      in A2 (p < 0.003). Steam sterilization seems to induce a higher cytokine release
      by mononuclear cells when a Cuprophan membrane is used. This finding may be
      related to a less physiologic action of the steam in the case of Cuprophan
      membranes. Further studies are needed to clarify this hypothesis.

PMID- 12072112
TI  - Utility of a peritoneal dialysis leukocyte test strip in the diagnosis of
      peritonitis.
AB  - Expeditious diagnosis of peritonitis remains a significant goal in the management
      of patients maintained on peritoneal dialysis. Several attempts to use leukocyte
      esterase reagent strips to diagnose peritonitis have been described. In this
      study we examined the usefulness of a new reagent strip, the PeriScreen Test
      Strip, in the diagnosis of peritonitis. A series of 72 peritoneal effluent
      samples obtained from 22 maintenance peritoneal dialysis patients is reported. In
      this study, the test strips had a sensitivity of 100% and a specificity of 98.3%
      as compared to an abnormal leukocyte count. Thus, in the diagnosis of peritonitis
      we believe that the PeriScreen Test Strip can be used as a simple bedside
      screening test to exclude peritonitis in peritoneal dialysis patients.

PMID- 12072113
TI  - At least thirty-four days of animal continuous perfusion by a newly developed
      extracorporeal membrane oxygenation system without systemic anticoagulants.
AB  - We developed an extracorporeal membrane oxygenation (ECMO) system with high
      antithrombogenicity and durability characteristics for prolonged continuous
      cardiopulmonary support. The oxygenator consists of a special hollow-fiber-type
      polyolefin gas-exchange membrane, which has an ultrathin dense layer in contact
      with the blood, in order to prevent plasma leakage during protracted use
      (Platinum Cube NCVC). The centrifugal pump (RotaFlow) is free of seals. The
      entire blood-contacting surface of the system is coated with a newly developed
      heparin material (Toyobo-NCVC coating). We performed a venoarterial bypass in a
      goat, and the ECMO system was driven for 34 days without systemic anticoagulants.
      Plasma leakage from the oxygenator did not occur, and sufficient gas exchange
      performance was maintained. Thrombus formation was hardly observed in the ECMO
      system except in the casing margins of the oxygenator. This ECMO system showed
      potential for long-term cardiopulmonary support with minimal or no use of
      systemic anticoagulants.

PMID- 12072115
TI  - An in vitro methodology for evaluating the mechanical properties of aortic
      vascular prostheses.
AB  - The main problem in the replacement of pathological segments of the aorta with
      vascular prostheses consists of matching the fluid admittance of the host artery
      and the graft. This mismatch results from the different compliance between
      natural and prosthetic vessels and from the plastic dilatation of the prosthesis
      diameter that occurs after implantation. An experimental procedure was set up for
      evaluating the mechanical properties of aortic vascular prostheses. An MTS 858
      MiniBionix testing machine was equipped with a purposely designed testing
      apparatus, which allows loading a ring-shaped prosthesis specimen with forces
      that can be related easily to the transmural pressure acting on the prostheses in
      vivo. The reference pressure waveforms are simulated from a lumped parameter
      model of the cardiovascular system. Preliminary tests on 3 different (woven, warp
      knitted, and carbon-coated warp knitted fabric) aortic prostheses point out a
      good reproducibility of the results. The fabric strongly affects the
      circumferential elasticity and the dimensional stability of the graft. Simulation
      of hypertension promotes larger diameter dilatation and reduction in compliance.
      Agreement between in vitro and clinical diameter measurements has been assessed
      for 8 prosthesis samples and found to be adequate. This method is thus a
      potentially useful means for preclinical evaluation of compliance of vascular
      prostheses for the purpose of matching to native vessels.

PMID- 12072116
TI  - Is roller pump induced tubing rupture a clinical possibility?
AB  - We analyzed the effects of variations in the diameter of silicone rubber and
      polyvinyl chloride (PVC) tubings on the likelihood of tubing rupture during
      modeling of accidental arterial line clamping in cardiopulmonary bypass (CPB)
      with a roller pump. A closed CPB circuit constructed with a roller pump was
      tested with both PVC and silicone rubber tubings of 1/2, 3/8, and 1/4 inch
      internal diameter. Arterial line pressure was monitored, and an occlusive clamp
      was placed across the tubing distal to the pressure monitor site to model an
      accidental arterial line occlusion. A charge coupled device camera with 512
      (horizontal) x 492 (vertical) pixels was installed above the roller pump to
      measure tubing diameters at pump outlet where the maximum deformations
      (distension) of the tubings occurred. Quantitative measurement of the changes of
      tubing diameters with the change of arterial line pressure was performed using
      computerized image processing techniques. A visible change of tubing diameter was
      generally noticeable by around 250 psi of arterial line pressure, which was
      already very high. By 1,500 psi, the PVC tubings showed an increase of diameter
      between 5% to 10% while the silicone rubber tubings showed an increase between
      20% to 25%. Silicone rubber tubings of all sizes showed greater distensibility
      than PVC tubings of equivalent size. In conclusion, although roller pump induced
      tubing rupture remains a theoretical problem during CPB in terms of the inherent
      mechanism of the pump, in reality such an occurrence is impossible in real
      clinical conditions.

PMID- 12072117
TI  - Proceedings of the 2nd European Congress on Violence in Clinical Psychiatry, June
      2001, Stockholm, Sweden.

PMID- 12072114
TI  - Hypothermia with heparin-coated circuits and low dose systemic heparinization in
      neurosurgery.
AB  - The purpose of this study was to evaluate the safety of profound hypothermic
      circulatory arrest with heparin-coated circuits and low dose systemic
      heparinization in the treatment of cerebral aneurysms. Surgery for giant
      intracranial aneurysms not operable using standard neurosurgical techniques was
      performed in 8 patients. All patients were placed on cardiopulmonary bypass using
      the closed-chest technique, except for the first patient who underwent open-chest
      bypass. Heparin was administered systemically (3,000 IU) and into the circuit
      (1,500 IU). Total circulatory arrest was begun at 20 degrees C. The D-dimer,
      alpha2 plasmin inhibitor-plasmin complex, thrombin-antithrombin III, and beta
      thromboglobulin concentrations were measured to evaluate the changes in the
      coagulation and fibrinolytic systems during bypass. There were no neurologic or
      cardiac complications. None of the indicators of platelet activation,
      coagulation, or fibrinolysis were elevated. Hypothermic circulatory arrest
      combined with heparin-coated circuits and low dose systemic heparinization is
      safe for use in neurosurgery.

PMID- 12072118
TI  - A public-health perspective on violence.
AB  - OBJECTIVE: To describe how specific theories and methods used in public health,
      especially regarding injuries, are related to violence. METHOD: Theories and
      preventive work in injury research (above accidents) are presented and related to
      violence. RESULTS: Registration of injuries and an interest in the environment
      are seen as specific for injuries. In prevention there is a focus on community
      work and the concept of 'a safe community' has been developed. Haddon's matrix
      offers a foundation for theoretical injury research. It is formed by cross
      tabulating the trichotomy of host-agent-environment against a time dimension.
      CONCLUSION: One practical and one theoretical model on how violence might be seen
      as an injury have been demonstrated. No clear evaluation has been made of the
      practical model up to now. The theoretical model has the advantage that the model
      makes it easier to get a more comprehensive picture of how different factors
      influence violence.

PMID- 12072119
TI  - Alcohol's role in domestic violence: a contributing cause or an excuse?
AB  - OBJECTIVE: This paper reviews evidence regarding the deviance disavowal approach
      to alcohol-related violence. It focuses on whether alcohol intoxication is used
      to excuse domestic violence, and whether this can explain alcohol/violence
      association. METHOD: Four hypotheses derived from the deviance disavowal approach
      were identified, including (i) people accept alcohol as a cause of violence; (ii)
      people attribute less blame and punishment to intoxicated aggressors than to
      sober aggressors; (iii) the belief that alcohol causes or excuses violence should
      be associated with and predict the occurrence of alcohol-related domestic
      violence; and (iv) the administration of a placebo should increase aggressive
      behaviour. RESULTS: The review suggested that some people do accept alcohol as a
      cause of violence, but that alcohol does not appear to mitigate blame, and this
      belief is not longitudinally predictive of violence. CONCLUSION: The evidence for
      a deviance disavowal model of alcohol and domestic violence appears quite weak.

PMID- 12072120
TI  - Preventing men's violence against women.
AB  - OBJECTIVE: The treatment and prevention of men's violence against women has
      increasingly been recognized as an issue not only for the criminal justice but
      also for the health and public health sectors. It is necessary to determine how
      health care can avoid accelerating women's 'entrapment' in a violent situation
      and to contribute to empowering them to take proactive steps. METHOD: Research
      and experience reveal how the nature of domestic violence can lead to health care
      playing a preventive role. The responsible body for health care in Stockholm, the
      Stockholm County Council, is one of several public authorities involved in a
      county-wide initiative called Operation Kvinnofrid, which has focused on internal
      training programmes as well as public poster campaigns. RESULTS: Public awareness
      campaigns in combination with internal training programmes do have an impact,
      especially where political and management will is clear. CONCLUSION: Heightened
      awareness among the public, enhanced skills among health workers, and multiagency
      coordination of the response to men's violence against women are essential
      elements of the long-term prevention of this violence.

PMID- 12072121
TI  - Bullying in the school environment: an injury risk factor?
AB  - OBJECTIVE: To describe a research project assessing the role of bullying at
      school as an injury trigger and the modification effect of the socio-economic
      environment of the victims. Preliminary results are also presented. METHOD: A
      case-crossover and a case-referent design were combined. The study base consisted
      of all children aged 10-15 years residing in the Stockholm county in 2000-02.
      Cases were recruited at the county's children hospital and interviewed shortly
      after the injury, using a specially designed questionnaire. RESULTS: Preliminary
      analyses (261 interviews) reveal that about two injured children out of 10
      reported having been bullied during the school term. Also, one out of 10 had been
      bullied shortly enough before the injury for bullying to be considered as a
      trigger. The circumstances of occurrence of those injuries varied. CONCLUSION:
      Bullying, apart from being frequent in the school environment, is quite likely to
      act as an injury trigger.

PMID- 12072122
TI  - Socio-economic differences in intentional injuries: a national study of Swedish
      male and female adolescents.
AB  - OBJECTIVE: To measure socio-economic differences in intentional injuries among
      Swedish adolescents. METHOD: A cross-sectional study, based on linkage of records
      from national registers, considering injuries incurred by all adolescents
      domiciled in Sweden in 1990-94. Absolute and relative differences between
      adolescents from four household socio-economic groups (SEGs) were measured,
      considering separately males and females, two age categories (10-14 and 15-19
      years) and injuries caused by interpersonal violence and self-inflicted injuries.
      RESULTS: Absolute differences (in injury incidence) between SEGs were greatest
      for self-inflicted injuries, among older female adolescents. There were clear
      social gradients in all instances, but relative differences (relative risks)
      reached a peak for interpersonal violence among younger adolescents, for both
      boys and girls. CONCLUSION: There is a clear association among Swedish
      adolescents between type of intentional injury and gender, with absolute
      differences remarkably wide for self-inflicted injuries. For a given age
      category, gender-specific social gradients are quite comparable within diagnosis.

PMID- 12072123
TI  - Psychological impact of torture: a 3-month follow-up of mass-evacuated Kosovan
      adults in Sweden. Lessons learnt for prevention.
AB  - OBJECTIVE: To study the impact of torture on symptomatology among mass displaced
      adults. METHOD: A sample (total 131; 70 females, 61 males) of mass displaced
      adults from Kosovo, in Sweden, completed 3 months after a baseline study on
      trauma experiences and perceived symptoms, self-rated instruments measuring
      psychiatric symptoms, aggression and coping. RESULTS: Torture is associated with
      poor coping (manageability); depression, anxiety and aggression are associated
      with post-traumatic stress disorder. All psychiatric symptoms and poor coping
      (but not aggression) are associated with being female. Limitations of the study
      include a relatively small sample. Ongoing trauma and stress before repatriation
      may also influence the responses. Several lessons learnt for prevention are
      discussed. CONCLUSION: Anger and hostility are important consequences of torture.
      Further research is necessary to understand the associations among coping
      strategies, psychiatric symptoms, aggression, torture experience and gender over
      time after repatriation or applying for asylum.

PMID- 12072124
TI  - More than zero tolerance? Burnout and tolerance for patient aggression amongst
      mental health nurses in China and the UK.
AB  - OBJECTIVE: The aim of the study was to examine attitudes toward patient
      aggressive behaviour amongst mental health nurses in China and the UK and the
      relationship between these attitudes and burnout. The UK government policy of
      'zero tolerance' of patient aggression may conflict with practitioner attitudes
      and could potentially increase the risk of aggression occurring. METHOD: Two
      surveys of mental health nurses were conducted, one in the People's Republic of
      China and one in the UK using the Perceptions of Aggression Scale (POAS). The UK
      sample also completed the Maslach Burnout Inventory (MBI). RESULTS: Some nurses
      in both groups agreed that patient aggression could sometimes have positive
      benefits. A sense of personal accomplishment at work (MBI) was significantly
      associated with a tendency to endorse positive statements about aggression.
      DISCUSSION: Nurses seem to have a complex set of attitudes toward this issue that
      do not simply equate with 'zero tolerance'.

PMID- 12072125
TI  - Management of violence in the workplace: a New Zealand survey.
AB  - OBJECTIVE: To estimate the rate of adverse events to staff, to survey the use of
      various preventative measures, and to assess any association between these
      factors and the reported event rate. METHOD: An anonymous postal nation-wide
      survey of violence reported to managers of psychiatric units in New Zealand.
      RESULTS: The mean rate of adverse event per 100 full time equivalent staff was
      16.2 (range 0-187) for property damage, 16.3 (range 0-204) for attempted assault,
      12 (range 0-194) for physical attack, 1.3 (range 0-33) for sexual harassment and
      1.1 (range 0-17) for stalking. Inpatient units, the use of pocket alarms, and
      training in de-escalation were associated highly with an increase risk of adverse
      events. CONCLUSION: There is a high variation in the rate of violence. The issue
      of increased rate of events with certain interventions will require further
      research.

PMID- 12072126
TI  - Prediction of violent recidivism.
AB  - OBJECTIVE: To describe the changes and improvements in accuracy of the prediction
      of violent recidivism. METHOD: The evolution of better prediction models is
      described by reviewing the more significant methods used and referring to the
      results of their application. RESULTS: Development of instruments such as the
      Psychopathy Checklist-Revised, the Violence Risk Assessment Guide (VRAG), the HCR
      20 and the multiple-item comprehensive questionnaire of Monahan and Steadman has
      substantially improved accuracy in risk assessment. The presence of full-blown
      psychopathy has proven itself a better predictor of violence than has a diagnosis
      of antisocial personality disorder according to the Diagnostic and Statistical
      Manual (DSW-IV). Shortcomings to the efficacy of the current instruments stem
      from the difficulty in detecting violence-proneness in persons who eventually
      assault or murder one or two persons (usually family members), but who have no,
      or a limited, record of past violence. Persons from affluent backgrounds are more
      adept at evading arrests or convictions than are the poor. Adolescent sons abused
      by parents are at risk to commit violent acts later on, but the community has
      little power to detect or intervene until these acts are committed. CONCLUSION:
      Prediction of violence has significantly improved over the last 20 years, thanks
      to the development of objective instruments of risk assessment.

PMID- 12072127
TI  - Community forensic psychiatry: restoring some sanity to forensic psychiatric
      rehabilitation.
AB  - OBJECTIVE: To review clinical and legal paradigms of community forensic mental
      health care, with specific focus on New Zealand, and to develop a clinically
      based set of guiding principles for service development in this area. METHOD: The
      general principles of rehabilitating mentally disordered offenders, and assertive
      community care programmes were reviewed and applied to the law and policy in a
      New Zealand forensic mental health setting. RESULTS: There is a need to develop
      comprehensive community treatment programmes for mentally disordered offenders.
      The limited available research supports assertive community treatment models,
      with specialist forensic input. Ten clinically based principles of care provision
      important to forensic mental health assertive community treatment were developed.
      CONCLUSION: Deinstitutionalization in forensic psychiatry lags behind the rest of
      psychiatry, but can only occur with well-supported systems in place to assess and
      manage risk in the community setting. The development of community-based forensic
      rehabilitation services in conjunction with general mental health is indicated.

PMID- 12072128
TI  - The quantitative risk of violent crime and criminal offending: a case-control
      study among the offspring of recidivistic Finnish homicide offenders.
AB  - OBJECTIVE: To study if later risk of violent offending and criminality among high
      risk children can be estimated quantitatively on the basis of parental crimes.
      METHOD: The criminal and prison records of the offspring (N=11) of homicide
      recidivists (N=36) were compared with data from controls (N=220) who were matched
      for sex, domicile of birth and date of birth and death. RESULTS: The risk (odds
      ratio) was increased up to 24-fold for violent crimes (P=0.01), and up to 17-fold
      for criminality (P=0.0008) among the offspring of homicide recidivists.
      CONCLUSION: The quantitative risk of a child for later violent offending and
      criminality can be estimated on the basis of parental homicide recidivism. This
      kind of method could be used to choose target groups for early preventive
      interventions, and to study the effectiveness of prevention.

PMID- 12072129
TI  - A comparison of risk factors for habitual violence in pre-trial subjects.
AB  - OBJECTIVE: Pre-trial referrals to the Valkenberg Hospital forensic unit over a 6
      month period were studied. Habitually violent offenders were compared with those
      with no history of violence. METHODS: Risk factors known to be associated with
      violent behaviour were elicited, i.e. demographics, behaviour during index
      offence (such as impulsivity, identity of victim, use of weapon, accomplices,
      intoxication, psychotic symptoms), psychiatric and family histories, history of
      suicide attempts, past child abuse, head injury, criminal record, psychiatric
      diagnosis and presence of medical disorders. EEG's, Barratt's Impulsivity,
      Zuckerman's Sensation Seeking and Mini-Mental Scales were administered. Behaviour
      in the ward during the 30 days was also appraised. Logistic regression models
      were used to determine relative risks. RESULTS: There were 155 subjects; 89.7%
      were male, 71.6% were single and 58.7% were unemployed. For 44.5% the index
      offence was violent, and 9.7% had committed sexual offences; 61.9% had histories
      of habitual violence. A psychotic disorder was diagnosed in 32.3% and a
      personality disorder in 48.4%. Habitually violent subjects were distin- guished
      by a history of issuing threats (OR=3.68; CI=3.19-4.16; P=0.000), delusions of
      persecution (OR=3.43; CI=2.67-4.17; P=0.001), history of conduct disorder
      (OR=1.95; CI=1.70-2.19; P=0.006), alcohol/substance abuse (OR=2.08; CI=1.53-2.61;
      P=0.008) and violent index offence (OR=1.66; CI=1.54-2.61; P=0.035). CONCLUSION:
      This seems to confirm the relationship between threats, feeling threatened,
      psychosis, a history of antisocial behaviour and alcohol abuse.

PMID- 12072130
TI  - Criminal behavior of forensic and general psychiatric patients with
      schizophrenia: are they different?
AB  - OBJECTIVE: This study was designed to compare the rate of past criminal behavior
      among male patients being discharged from forensic and general psychiatric
      hospitals in four countries. METHOD: Discharged consecutive patients from eight
      sites, four general and four forensic psychiatric, were included and asked for
      participation. Transcripts of past criminal behavior were available for this
      study. Analyses were limited to men with schizophrenia. RESULTS: One in five of
      the general psychiatric patients had a criminal record. The criminal histories of
      the offenders in the general and forensic hospitals were similar, except that all
      patients who had killed were treated in forensic hospitals. CONCLUSION: The
      results point to the need to assess the risk of violent behavior among general
      psychiatric patients in order to provide them with appropriate treatments
      designed to prevent criminal recidivism.

PMID- 12072131
TI  - Risk//need analysis in juvenile delinquents: an integrated multiprofessional
      longitudinal approach--a clinical pilot project.
AB  - OBJECTIVE: A clinical pilot project with the aim of performing a risk/need
      analysis in juvenile delinquents is presented. The main objective of this project
      was to test the feasibility of performing independent risk predictions by a
      forensic psychiatric team. METHOD: The organization, which involves a forensic
      psychiatric team, is described. Risk factors, risk prediction checklists and an
      analysis of crime characteristics and certain personality features with possible
      criminogenic implications are discussed. RESULTS: The feasibility of the project
      organization has been confirmed. CONCLUSION: It appears to be possible for an
      independent forensic psychiatric team to perform risk/need analysis in juvenile
      delinquents. The integration of clinical factors involving collaboration with
      staff at the juvenile detention home and checklists for risk prediction are
      recommended. Long-term follow up would make it possible to relate certain risk
      factors and evaluate risk management procedures to relapse in criminal behaviour
      and beneficial outcome, respectively.

PMID- 12072132
TI  - Relapse in violent crime in relation to cerebrospinal fluid monoamine metabolites
      (5-HIAA, HVA and HMPG) in male forensic psychiatric patients convicted of murder:
      a 16-year follow-up.
AB  - OBJECTIVE: Our purpose was to investigate if low levels of cerebrospinal fluid
      (CSF) monoamine metabolites of 5-HIAA, HVA and HMPG predict relapse in violent
      crimes. METHOD: Relapse in crime and level of CSF monoamine metabolites (5-HIAA,
      HVA and HMPG) was studied in a group of 29 murderers. The follow-up was 16 years.
      RESULTS: Fourteen of the 29 murderers were convicted of crime; nine of them
      committed violent crimes; one was convicted of a new murder. The differences in
      mean CSF monoamine metabolites were lower in subjects who relapsed into any type
      of crime, but only the difference in mean CSF HVA was statistically significant.
      CONCLUSION: The risk to commit new murder is very small in males who earlier have
      been convicted of murder. Low levels of CSF HVA is associated with an increased
      risk for relapse in any type of crime.

PMID- 12072133
TI  - Understanding the abnormal by studying the normal.
AB  - OBJECTIVE: In the present paper we ask whether it is meaningful to study
      psychopathic traits in non-referred youths and whether this kind of research can
      be used to understand the development of criminal full-blown psychopathy. METHOD:
      We review studies that have investigated the utility of assessing psychopathic
      traits in non-referred samples of youths. RESULTS: Research shows that
      psychopathic traits in non-referred youths manifest similarly to how they are
      manifested among incarcerated offenders, as indicated by similarities in factor
      structures. Also, psychopathic traits relate similarly to frequent, violent
      antisocial behavior in non-referred youths as among adult and adolescent
      institutionalized criminal offenders. Thus, the differences between the non
      referred conduct-problem youths exhibiting a psychopathic personality pattern and
      the incarcerated, criminal youths identified as psychopathic seem to be
      quantitative rather than qualitative. CONCLUSION: It is concluded that research
      on non-referred youth samples can provide important knowledge about the processes
      that underlie the development of psychopathic traits and how this development can
      be prevented. Implications for future research and intervention and prevention
      are discussed.

PMID- 12072134
TI  - On the operationalization of psychopathy: further support for a three-faceted
      personality oriented model.
AB  - OBJECTIVE: This study is an attempt to compare two alternative models of
      psychopathy (PCL-R); (i) the traditional 17-item two-factor model where the first
      factor describes a deceitful, manipulative and callous, unemotional dimension and
      the second factor describes the impulsive, irresponsible and antisocial
      behavioral lifestyle dimension; and (ii) a recently proposed 13-item three-factor
      model involving an interpersonal facet, an affective facet and a behavioral
      facet. METHOD: Exploratory and confirmatory factor analyses of PCL-R scores on a
      sample of 293 adult male violent offenders were conducted. RESULTS: The results
      of the exploratory factor analysis showed that the 13 items yielded three easily
      interpretable factors: an interpersonal factor, an affective factor and a
      behavioral/lifestyle factor. Through confirmatory factor analysis we showed that
      this model had a significantly closer fit to the data than the classical 17-item,
      two-factor model of the PCL-R. CONCLUSION: The study supports the three-faceted
      model of psychopathy.

PMID- 12072135
TI  - Psychopathy and violent recidivism among young criminal offenders.
AB  - OBJECTIVE: To investigate the predictive validity of psychopathic personality
      traits (assessed with the revised psychopathy checklist, PCL-R; Hare, 1991) for
      violent criminal recidivism among young offenders. METHOD: The relationship
      between PCL-R psychopathy and violent re-offending was studied in 98 young
      (M=18.40, range 15-20 years) violent and sex offenders subjected to forensic
      psychiatric evaluation in Sweden during 1988-95. Subjects were followed during
      detainment and for 24 months in the community to first reconviction for a violent
      offence. RESULTS: We found a modest but significant association between PCL-R
      scores and violent recidivism, almost exclusively accounted for by behavioural
      criteria. Among 13 possible confounders tested, conduct disorder before age 15
      and a young age at first conviction eliminated the relationship between
      psychopathy and violent recidivism in pair-wise logistic regression models.
      CONCLUSION: PCL-R psychopathy may be a less valid predictor for violent criminal
      recidivism among severe youthful offenders than among adult offenders.

PMID- 12072136
TI  - Adult psychopathy and violent behavior in males with early neglect and abuse.
AB  - OBJECTIVE: Within a Swedish longitudinal project, possible implications of
      childhood neglect and/or abuse on adult psychopathy checklist (PCL) scores and
      violent offending were studied. METHOD: The subjects were males (n=199),
      recruited from a socially high-risk neighborhood and grouped on an index variable
      of victimization, yielding high (n=110) and low victimization (n=89) groups. To
      highlight a possible comorbidity of all three problems in the same persons, a
      combined dimensional and categorical (configural frequency analysis, CFA)
      approach was applied. RESULTS: The high victimization subjects exerted
      significantly more violence, as did subjects with high PCL scores. Furthermore,
      in the CFA two significant 'types' were found: one type indicating that 'high'
      victimization in childhood is closely linked to later 'extensive' violence and
      'high' PCL scores at adult age in the same individuals; the other supporting a
      frequent co-occurring of 'low' victimization in childhood, 'none or minor' later
      indications of violence and 'low' adult PCL scores. CONCLUSION: The results point
      to possible underlying mechanisms linked to all three problems characterizing the
      affected subjects.

PMID- 12072137
TI  - Measuring aggression with the staff observation aggression scale--revised.
AB  - OBJECTIVE: The staff observation aggression scale (SOAS; Palmstierna & Wistedt,
      1987) was developed to measure nature, number, as well as severity of aggressive
      incidents. In 1999, a revised version of the SOAS (i.e. the SOAS-R), with a more
      fine-grained severity scoring system, was presented. In the current paper, the
      development and testing of the revised severity scores of the SOAS-R are
      addressed. METHOD: In two consecutive studies, staff members recorded inpatient
      aggression on SOAS-R forms, but also expressed their opinion about the severity
      of incidents on 100 mm visual analogue scales (VASs). Correlations were
      calculated between SOAS and SOAS-R severity scores, on the one hand, and clinical
      judgements of severity, on the other. RESULTS: In both studies, revised SOAS
      severity scores were more closely related to clinical judgements of aggression
      severity than the original ones. CONCLUSION: The SOAS-R is a promising tool for
      research on the prevalence, severity and determinants of inpatient aggression.

PMID- 12072139
TI  - Issues in the measurement of violent incidents and the introduction of a new
      scale: the 'attacks' (attempted and actual assault scale).
AB  - OBJECTIVE: To review the strengths and weaknesses of existing violent incident
      measures, and introduce a new scale, the 'attacks'. The new scale provides an
      objective measure of incident severity and focuses on interpersonal physical
      violence in isolation from other behaviours. METHOD: The new scale was piloted on
      six psychiatric wards in the East End of London over a period of 16 weeks.
      Descriptive data were obtained and validated against official violent incident
      records. RESULTS: There were 40 incidents by 21 aggressive patients, most of
      which occurred on the psychiatric intensive care unit. Striking assaults
      predominated. Continuous holding of the patient by nurses occurred after 17% of
      incidents. Special observation was also used as a subsequent management method in
      more than half of the incidents. CONCLUSION: The scale is acceptable to nurses
      and valid. Interesting questions are raised about the content of training for
      staff in the prevention and management of violent incidents.

PMID- 12072138
TI  - The Broset violence checklist (BVC).
AB  - OBJECTIVE: The Broset violence checklist (BVC) is a short-term violence
      prediction instrument assessing confusion, irritability, boisterousness, verbal
      threats, physical threats and attacks on objects as either present or absent. The
      aim of this paper is to describe the evolution and usefulness of the BVC. METHOD:
      This paper reviews studies on the BVC and discusses implications for further
      research. RESULTS: Empirical research has shown that it has moderate sensitivity
      and high specificity with an adequate inter-rater reliability. CONCLUSION: The
      BVC is a useful instrument for predicting inpatient violence within the next 24-h
      period. The psychometric properties of the instrument are satisfactory. Results
      from ongoing studies will give important information on cultural differences, the
      validity of the BVC in less well staffed wards, the clinical use of the checklist
      and its ability to predict violence throughout all the hospital stay.

PMID- 12072140
TI  - Perception of aggression among psychiatric nurses in Switzerland.
AB  - OBJECTIVE: To identify principal components and patterns in the perception of
      aggression by psychiatric nurses and to explore relationships between the
      perception of aggression and personal and workplace characteristics. METHOD:
      Seven hundred and twenty-nine nurses working in psychiatric inpatient departments
      of German-speaking Switzerland completed the perception of aggression scale
      (POAS). Data analysis included factor analysis, group comparisons and
      multivariate analysis of covariance. RESULTS: Two plausible factors were
      identified, representing different dimensions in the perception of aggression and
      accounting for 35% of the variance. Firstly, aggression is perceived as
      dysfunctional/ undesirable and, secondly, aggression is perceived as a
      functional/ comprehensible phenomenon. Only minor differences were found in the
      perception of aggression with regard to personal characteristics or work
      environment of the nurses. CONCLUSION: Nurses perceive aggression not just as a
      negative phenomenon. The perception of aggression as measured by POAS is
      independent of many characteristics expected to be related to the perception of
      violence, such as grade of education, work experience, etc.

PMID- 12072141
TI  - Perception of aggression, personality disorders and psychiatric morbidity in
      nursing students.
AB  - OBJECTIVE: To determine the relationship between perception of aggression,
      personality disorders and psychiatric morbidity. METHOD: Ninety nursing students
      were interviewed. A two-stage transversal analysis was used, the first stage
      using the Spanish version of the general health questionnaire (GHQ-28), the true
      false test of international personality disorders (IPDE) of Loranger, and the
      perception of aggression scale (POAS) of Jansen. For the second stage we used the
      Spanish version of the clinical interview schedule (CIS), and the full test of
      IPDE. RESULTS: Perception of aggression was mainly described as a violent
      reaction. There were no significant differences in the perception of aggression
      according to GHQ(+), CIS(+) and IPDE(+). There was a significant relationship
      between perception of aggression as violent reaction and gender. CONCLUSION:
      Aggression was perceived by our nursing students as a violent reaction. A
      significant relationship with gender was observed.

PMID- 12072143
TI  - Anabolic androgenic steroids and violence.
AB  - OBJECTIVE: To scrutinize the criminal career among users of anabolic androgenic
      steroids (AAS) with focus on a possible relationship between use of AAS and
      violent offences. METHOD: Prospective longitudinal follow-up of police records
      concerning known users of AAS. RESULTS: The present study describes five young
      men who started to use AAS with the primary motive of gaining muscle mass and
      strength and who subsequently got involved in criminal activities, including
      violent offences. One person showed deviant behaviour suggestive of conduct
      disorder at an early age. The other persons appeared to have low self-confidence,
      but had not been acting out during early adolescence. CONCLUSION: Use of AAS may
      constitute an increased risk of developing an antisocial life style with
      involvement in criminal violence.

PMID- 12072142
TI  - The effects of drug abuse on the stress responsive hypothalamic-pituitary-adrenal
      axis and the dopaminergic and endogenous opioid systems.
AB  - OBJECTIVE: Drugs of abuse have a significant impact on the stress responsive
      hypothalamic-pituitary-adrenal (HPA) axis and an abnormal response to stress may
      mediate the development or maintenance of addictive diseases. In animals, drugs
      of abuse, such as cocaine, lead to an activation of the HPA axis. Drugs of abuse
      also have an impact on the endogenous opioid system (EOS) and the dopaminergic
      system. Each of these systems has also been implicated in the mediation of
      aggressive behaviors. This brief report focuses on the effects of drugs of abuse
      on the stress responsive HPA, EOS and dopaminergic systems, and the role of these
      systems in mediating aggression and comorbidity of substance abuse and aggressive
      behaviors. METHOD: Rodents were administered either 'binge' pattern cocaine (15
      mg/kg x 3 each day) or the androgenic anabolic steroid nandrolone decanoate and
      the effects on mRNA levels, receptor binding and circulating levels of stress
      hormones were analyzed. RESULTS: Both cocaine and nandrolone decanoate
      significantly impact the HPA axis, the EOS and the dopaminergic systems.
      CONCLUSION: Drugs of abuse impact substantially the same neural systems that
      affect aggressive behavior.

PMID- 12072144
TI  - Effect of combined treatment with nandrolone and cocaine on the NMDA receptor
      gene expression in the rat nucleus accumbens and periaqueductal gray.
AB  - OBJECTIVE: Anabolic androgenic steroids (AAS) have been suggested to sensitize
      mechanisms involved in drug dependency and aggressive behaviour. Nucleus
      accumbens and periaqueductal gray (PAG) are believed to be critical in the
      functional anatomy of these two phenomena, which are partly mediated by the NMDA
      receptor. This study was undertaken in order to determine the relationship
      between the effect of AAS and cocaine (given alone or in combination) on the gene
      expression of the NMDA receptor subtype NR1 in the rat nucleus accumbens and PAG.
      METHOD: Male rats were subjected to 2 weeks of daily doses of cocaine and the
      anabolic-androgenic steroid nandrolone, administrated separately or in
      combination, and the effect on the mRNA expression for the NMDA receptor NR1
      subunit was studied by Northern blot analysis. RESULTS: In the nucleus accumbens,
      injection of cocaine alone and the combination of cocaine and nandrolone caused a
      significant decrease in the NR1 mRNA level compared with that of control rats.
      The combined treatment significantly down-regulated the transcript in the PAG
      compared with the groups injected with vehicle, nandrolone or cocaine alone.
      CONCLUSION: It was concluded that AAS combined with cocaine may induce additive
      increases in glutamatergic activity in these brain areas, supporting the notion
      that these steroids can sensitize mechanisms involved in the reward and the
      expression of aggression.

PMID- 12072145
TI  - Prediction of inpatient violence.
AB  - OBJECTIVE: An overview of studies on predictors and on the accuracy of prediction
      of inpatient violence should be given. METHOD: To date, the published data do not
      allow a systematic meta-analysis due to different sample characteristics,
      different measures and definitions of violence, and different time frames of
      observation. Published studies were reviewed regarding significant predictors of
      inpatient violence. RESULTS: Predictors of violence in institutional settings are
      different from predictors of violence in the community: variables such as sex,
      age, diagnosis and alcohol abuse play a minor role, while clinical and
      psychopathological variables are prominent. Only history of violence is a robust
      static predictor. The total level of positive and general psychotic symptoms
      seems to enhance the violence risk of inpatients, whereas results concerning
      specific features like delusions or command hallucinations are contradictory due
      to inevitable problems of sample selection. The accuracy of clinical predictions
      is better than chance but limited by the effects of therapeutic interventions and
      research artefacts. CONCLUSION: The author argues that more precise
      determinations of the violence risk in institutions will fail and that the role
      of environmental factors has often been underestimated.

PMID- 12072146
TI  - A model of aggression in psychiatric hospitals.
AB  - OBJECTIVE: Research of the determinants of inpatient aggression indicates that
      certain environmental hospital variables play a role in triggering aggression in
      psychiatric hospitals. Yet, how patient, staff and ward variables interact in
      eliciting aggression is not well understood. METHOD: On the basis of earlier
      findings, a model was proposed in which psychopathology and distorted cognitions
      of the patient are combined with environmental and communicational stressors that
      are specific for psychiatric wards. RESULTS: The proposed model elucidates how
      certain patient, staff and ward characteristics may interact in causing
      aggression. The model also emphasizes that repeated inpatient aggression may be
      the result of a vicious circle, i.e. inpatient violence is often followed by an
      increase in environmental and/or communication stress on the patient, thereby
      heightening the risk of a repeated outburst of violence. CONCLUSION: Although
      tentative, the model may shed light on the mechanisms that lead to (repeated)
      violence.

PMID- 12072147
TI  - Violence in a general hospital: comparison of assailant and other assault-related
      factors on accident and emergency and inpatient wards.
AB  - OBJECTIVE: This study sought to compare the characteristics of aggressive
      incidents occurring on inpatient (medical and surgical) wards with those
      occurring in the accident and emergency department in terms of assailant,
      employee and other factors. METHOD: A prospective interview-based survey design
      was adopted. Forty-eight assaulted staff were interviewed about 69 incidents
      within 7 days on average of the incident occurring. The presence or absence of
      various assailant, employee, situation, interaction and outcome factors derived
      from the UK Health Services Advisory Committee's model was compared between the
      two settings. RESULTS: Inpatient ward incidents were significantly more likely to
      have the following characteristics: female perpetrator, perpetrator aged over 70
      years, daytime occurrence in a restricted area, resolved by support from other
      health care staff. CONCLUSION: Aggression frequently occurs on inpatient (medical
      and surgical) wards of a general hospital. Aggression management training for
      staff working in both accident and emergency and inpatient settings should be
      cognisant of the similarities and differences within general health care
      specialisms.

PMID- 12072148
TI  - Comparing clinical risk assessments using operationalized criteria.
AB  - OBJECTIVE: To compare the clinical risk assessment of patients by psychiatrists
      working in different mental health service settings (low, medium and high
      security). METHOD: Operationalized criteria of clinical factors recognized as
      indicating risk of harm to others were developed into a simple checklist with
      explicit item descriptions and definitions (OP-RISK). This was used to compare
      risk assessments in a prospective cohort of 161 consecutive referrals to a high
      secure psychiatric hospital. RESULTS: Agreement on the risk posed by a patient
      between psychiatrists working outside and inside high secure services using
      unstructured clinical risk assessment was poor (kappa=-0.006). When OP-RISK was
      applied to the clinical risk assessments, agreement improved (kappa=0.742).
      CONCLUSION: Applying operationalized criteria to clinical risk assessment is
      useful in integrating different mental health service settings. The use of OP
      RISK may facilitate the referral process to tertiary care.

PMID- 12072149
TI  - Auricular acupuncture in prison psychiatric units: a pilot study.
AB  - OBJECTIVE: The study explores whether auricular acupuncture can be a viable
      treatment form for inmates in prison psychiatric units. METHOD: Inmates in a
      prison psychiatric unit and in a support unit for violent behavior were offered
      group treatment with auricular acupuncture three times a week over a period of 9
      months. Another prison psychiatric unit served as a control group. RESULTS:
      Twenty-two inmates received treatment, and 11 inmates received treatment for over
      8 weeks. Cortisol levels were higher for inmates in the support unit than for the
      other two groups. Inmates treated at least 25 times were prescribed fewer
      psycholeptic drugs than controls. Perceived autonomy increased for treated
      inmates in the psychiatric unit. Inmates treated for over 8 weeks experienced
      improved inner harmony and calm and better clarity over future plans. CONCLUSION:
      Acupuncture is a non-verbal form of treatment appropriate for prison psychiatric
      units. The treatment facilitates contact and complements other psycho-social
      treatment forms.

PMID- 12072150
TI  - Functional characteristics of cysteinyl-leukotriene receptor subtypes.
AB  - Cysteinyl-leukotrienes, i.e. leukotriene (LT) C4, D4 and E4, are inflammatory
      mediators and potent airway- and vasoconstrictors. Two different cysteinyl
      leukotriene receptors, CysLT1 and CysLT2, have been cloned and functionally
      characterised using potent CysLT1 receptor antagonists and the dual CysLT1/CysLT2
      receptor antagonist BAY u9773. However, the rank order of potency of the
      cysteinyl-leukotrienes at the CysLT receptors differs between tissues and
      studies, and a CysLT receptor classification based on agonist selectivity has not
      been established. In addition, the existence of more than two receptor subtypes
      for cysteinyl-leukotrienes has been suggested.

PMID- 12072151
TI  - Activation of B lymphocytes by GLIS, a bioactive proteoglycan from Ganoderma
      lucidum.
AB  - A bioactive fraction (GLIS) was isolated from the fruiting body of the fungus
      Ganoderma lucidum using successive chromatographic steps. GLIS is a proteoglycan
      and has a carbohydrate: protein ratio of 11.5 : 1. The carbohydrate portion is
      composed of seven different monosaccharides, predominantly D-glucose, D-galactose
      and D-mannose in the molar ratio of 3.0 : 1 : 1.GLIS stimulated the proliferation
      of mouse spleen lymphocytes, resulting in a three to four-fold increase in the
      percentage of B cells. GLIS also activated mouse spleen lymphocytes, and most of
      the activated cells were B cells. The B cells were enlarged, expressed CD71 and
      CD25 on the cell surface, and showed an increase in the secretion of
      immunoglobulin. Lymphocytes also showed a slightly increased production of IL-2,
      whereas the secretion of IL-4 was not influenced by GLIS. Furthermore, GLIS did
      not influence the intracellular Ca2+ concentration of lymphocytes, but it
      enhanced the expression of protein kinase C alpha and protein kinase C gamma in B
      cells. According to our results GLIS is a new B cell-stimulating factor.

PMID- 12072152
TI  - The awakening cortisol response: no evidence for an influence of body posture.
AB  - It has recently been reported that the orthostatic challenge associated with
      postural change from sitting to an upright position is stimulatory to the
      hypothalamic-pituitary-adrenal axis as evidenced by increased salivary free
      cortisol. This stimulatory influence is potentially a confound for the many
      psychoneuroendocrine studies for which salivary free cortisol is the main
      dependent variable. This particularly relates to laboratory psychosocial stress
      procedures in which subjects are invited to stand in order to deliver public
      speech and the studies which have explored the cortisol response to awakening in
      which postural shift has not been controlled for. We therefore examined, in a
      balanced cross over design whether the awakening cortisol response was influenced
      by standing, shortly after awakening or remaining supine during the response
      study period. In addition and in the same subjects we measured the cardiovascular
      response and saliva cortisol response to the orthostatic challenge of shifting
      from a supine to a standing position later in the diurnal cortisol cycle. The
      expected cortisol response to awakening was demonstrated but there was no
      evidence that the postural shift, supine to standing, confounded the response.
      This same postural shift later in the day induced the expected increase in heart
      rate but cortisol simply followed the circadian decline. Under the conditions of
      the present study we found no evidence that the postural shift supine to standing
      could induce a cortisol secretory episode such as to contribute towards the
      awakening response.

PMID- 12072153
TI  - Acute gliclazide administration enhances glucose and ketone body utilization in
      the perfused hind limb of normal and streptozotocin-diabetic rats.
AB  - Sulfonylureas are the most commonly used oral hypoglycemic agents. Their
      hypoglycemic actions are produced not only by stimulating insulin secretion but
      also by extrapancreatic mechanisms. Some groups have already demonstrated the
      extrapancreatic actions of sulfonylureas on carbohydrate metabolism in the liver,
      fat and muscle. In this study, we showed in an in situ perfused hind limb
      preparation of STZ-diabetic rats that gliclazide has an acute effect on ketone
      body and glucose utilization.

PMID- 12072154
TI  - Protective effect of resveratrol against oxidative stress in middle cerebral
      artery occlusion model of stroke in rats.
AB  - Free radicals have been implicated in neuronal injury during ischemia reperfusion
      in stroke. Trans resveratrol, a potent antioxidant, polyphenolic compound found
      in grapes and wines has recently been shown to have neuroprotective activity
      against oxidative stress in in vitro studies. In the present study the effect of
      chronic treatment of trans resveratrol was evaluated in focal ischemia induced by
      middle cerebral artery [MCA] occlusion in rats. Male Wistar rats were pretreated
      with trans resveratrol 20 mg/kg i.p. for 21 days and were subjected to focal
      ischemia by occlusion of MCA using intraluminal thread. After two hours of MCA
      occlusion reperfusion was allowed by retracting the thread. Animals were assessed
      for motor performance after 24 hours and subsequently rats were sacrificed for
      estimation of markers of oxidative stress [malondialdehyde [MDA] and reduced
      glutathione] and for evaluation of volume of infarction. Control group received
      vehicle and similar protocol was followed. Significant motor impairment, with
      elevated levels of MDA and reduced glutathione was observed in the vehicle
      treated MCA occluded rats. Treatment with trans resveratrol prevented motor
      impairment, rise in levels of MDA and reduced glutathione and also significantly
      decreased the volume of infarct as compared to control. The study provides first
      evidence of effectiveness of trans resveratrol in focal ischemia most probably by
      virtue of its antioxidant property.

PMID- 12072155
TI  - Expression of dopamine receptors and transporter in neuroendocrine
      gastrointestinal tumor cells.
AB  - C-11- or F-18-DOPA positron emission tomography (DOPA PET) is a new sensitive
      imaging technique for small neuroendocrine gastrointestinal tumors which
      evaluates the decarboxylase activity. To further characterize the dopaminergic
      system in neuroendocrine gastrointestinal tumor cells, we investigated the
      expression of both dopamine receptors and the transmembrane dopamine transporter
      (DAT) in the human neuroendocrine pancreatic cell line BON and in the
      neuroendocrine gut cell line STC-1. Both BON and STC-1 cells expressed mRNA of
      the dopamine receptors D2-D5 and DAT. mRNA of the dopamine receptor D1 was
      detected in BON cells only. Both in BON and STC-1 cells, expression of D2 and D5
      receptors and DAT was also demonstrated immunocytochemically. For functional
      receptor characterization intracellular cAMP levels ([cAMP]i) were determined.
      Whereas in STC-1 cells dopamine and the D1-like (D1/D5) receptor agonist SKF
      38393 increased [cAMP]i, [cAMP]i was decreased by dopamine or the D2-like (D2-D4)
      receptor agonist quinpirole in BON cells. Functional DAT activity was, however,
      not detected in either cell line. The presence of both dopamine receptors and of
      the DAT suggests an autocrine and/or paracrine function of dopamine in
      neuroendocrine gastrointestinal tumor cells. Yet neither the transmembrane
      dopamine transporter nor dopamine receptors are likely to contribute to positive
      DOPA PET imaging of neuroendocrine gastrointestinal tumors. However, these
      molecules may be of diagnostic importance when applying other dopaminergic system
      tracers.

PMID- 12072156
TI  - Effects of spontaneous or induced brain ischemia on vessel reactivity: the role
      of inducible nitric oxide synthase.
AB  - Short episodes of ischemia and reperfusion in various organs may protect the
      organ itself, and the heart both as an immediate and a delayed effect. The
      present study investigates whether a systemic protection of vascular function
      occurs during adaption to ischemia. Brain ischemia was induced by bilateral
      ligation of the internal carotid arteries in C57BL6 mice, and 24-36 hours later
      rings of the thoracic aorta were mounted to study in vitro relaxation and
      contraction, or proteins were extracted for immunoblotting for endothelial nitric
      oxide synthase (eNOS) or inducible NOS (iNOS). eNOS decreased, while iNOS
      increased in the aortic wall after carotid artery ligation. In vitro contraction
      to increasing concentrations of prostaglandin F(2alpha) (PGF(2alpha)) was
      attenuated, while relaxation to acetylcholine (ACh) was enhanced. The latter was
      abolished by the iNOS-inhibitor aminoguanidine. When brain ischemia was induced
      in iNOS deficient mice, an increase of aortic eNOS was found 24 hours later. The
      ischemia-induced attenuated relaxation to PGF(2alpha) and enhanced relaxation to
      ACh were abolished. Aortic rings from mice with severe atherosclerosis
      (apolipoprotein E and low density lipoprotein receptor double knockout (ApoE/LDLr
      KO) mice) and spontaneous ischemic events in the heart or brain in vivo were also
      studied. Spontaneous ischemic events in ApoE/LDLr KO animals did not influence
      iNOS and eNOS in the vessel wall. A reduced contraction to PGF(2alpha) was
      observed, but relaxation to ACh was unchanged. These findings suggest that
      induced brain ischemia as a model of delayed, remote preconditioning protects
      vessel reactivity, and this protection is mediated by iNOS.

PMID- 12072157
TI  - Three different pathways for human LDL oxidation are inhibited in vitro by water
      extracts of the medicinal herb Achyrocline satureoides.
AB  - In this study we investigated the antioxidant properties of one herbal
      preparation widely used in complementary and alternative medicine in large areas
      of the world: Achyrocline satureoides (AS), popularly known as "marcela".
      Although rich in flavonoids, the ethnopharmacological uses of this plant do not
      include atherosclerosis prevention. Furthermore, no study had been conducted so
      far exploring the antioxidant activity of Achyrocline satureoides vis-a-vis human
      LDL oxidation, which is the compelling issue in pinpointing potential
      cardioprotective new uses for a traditional remedy. We explored the effects of AS
      extracts on human LDL oxidation, employing 3 different systems which are thought
      to play a role in oxidation of LDL in the arterial wall: copper, peroxynitrite,
      and lipoxygenase. Oxidation was monitored by conjugate dienes, TBARS formation
      and aggregation of apoB using SDS-PAGE. In copper-initiated oxidation a dose
      dependent inhibition of the initiation and propagation of lipid oxidation is
      shown by an increase in the lag phase for conjugate diene production which was 60
      +/- 15 min in the absence and 120 +/- 20 min in the presence of 4 microg/ml AS
      extracts (p < 0.001). TBARS production was reduced by 95% after 3 h incubation at
      5 microg/ml. Aggregation of apoB was abolished at the same concentrations. SIN-1
      (3-morpholinosydnonimine) produces peroxynitrite via generation of NO and O2-.
      When LDL was incubated in its presence, a milder oxidation was observed as
      compared with Cu2+, and AS produced over 70% inhibition. Finally, we show a
      striking dose-dependent inhibitory effect of lipoxygenase conjugate diene
      production, which is over 95% at AS concentrations of 5 microg/ml. When compared
      with other antioxidants, AS effect is greater but in the same order of magnitude
      than that of ascorbic acid and similar to the popular herbal tea Ilex
      paraguariensis. In all three systems employed an effect is already substantiated
      at a concentration of the AS extract of 4 microg/ml, which corresponds to a 1/100
      dilution of the preparations usually drunk.

PMID- 12072158
TI  - 5-HT1A receptor blockade and the motivational profile of ethanol.
AB  - Although several serotonin (5-HT) receptor subtypes influence ethanol
      consumption, the motivational mechanisms underlying these changes remain unclear.
      The present experiments characterized the rewarding, aversive and stimulant
      effects of ethanol in combination with a specific 5-HT1A receptor antagonist
      (pindobind-5HT1A). In a place conditioning study, adult male Swiss-Webster mice
      received 6 parings of a distinctive tactile stimulus with either 2 g/kg ethanol,
      2.5 mg/kg pindobind-5HT1A, or both drugs in combination. Ethanol-conditioned
      preference for the tactile cue was enhanced in mice also receiving pindobind
      5HT1A, which did not produce cue preference in the absence of ethanol. In a taste
      conditioning study, Swiss-Webster mice received 4 trials consisting of access to
      a distinctive NaCl flavor followed by either 4 g/kg ethanol, 2.5 mg/kg pindobind
      5HT1A, or both drugs. As expected, ethanol produced avoidance of the flavor.
      Pindobind-5HT1A did not reduce or enhance ethanol-conditioned flavor aversion. In
      a study characterizing locomotor activity, 2 g/kg ethanol produced stimulation,
      which was enhanced after 10 daily treatments. Locomotor sensitization was not
      altered by co-treatment with pindobind-5HT1A. Overall, the present results show
      specific effects of 5-HT1A blockade on ethanol reward.

PMID- 12072159
TI  - Effect of beta-Carotene on the development of the solid Ehrlich tumor in mice.
AB  - The effect of beta-Carotene on the development of the solid Ehrlich tumor in
      BALB/c mice was investigated. Male mice received orally, on alternate days, three
      different doses of beta-Carotene (1, 3.5 or 7 mg/100 g) or corn oil as the
      control. This protocol started 14 days before tumor inoculation (1.75 x 10(5)
      cells) into mouse footpad and lasted until 10 days after. The tumor growth was
      evaluated by daily measurement of the footpad thickness, and the tumor mass was
      evaluated morphometrically. The proliferation rate of tumor was investigated by
      counting PCNA (proliferating cell nuclear antigen) positive nuclei in the 10th
      day of the tumor development. Histopathological examination of the lymphoid
      tissue: thymus, spleen and popliteal lymph node were also performed. beta
      Carotene treatment, at dose 3.5 mg/100 g, increased the tumor growth,
      proliferative rate and the relative weight of popliteal lymph nodes, showing up
      an adverse effect only when this intermediate dose was used. No effects were
      obtained when the smaller (1,0 mg/100 g) or the higher (7.0 mg/100 g) doses were
      used. These results suggest that depending on the dose, beta-Carotene may
      determine an undesirable effect upon the tumor growth. This should be taken into
      account in chemopreventive experiments and human applications.

PMID- 12072160
TI  - The role of T-type calcium channels in morphine analgesia, development of
      antinociceptive tolerance and dependence to morphine, and morphine abstinence
      syndrome.
AB  - Involvement of T-type voltage dependent Ca2+ channels (VDCCs) on morphine
      antinociception, in the development of tolerance and dependence to morphine, and
      naloxone-precipitated abstinence syndrome in morphine dependent mice was examined
      by using mibefradil, a T-type VDCCs blocker. Mice were rendered tolerant and
      dependent on morphine by subcutaneous (s.c.) implantation of a morphine pellet
      containing 75 mg of morphine base for 72 hr. The tail-flick test was used to
      assess the nociceptive threshold. Coadministration of acute mibefradil (10 mg/kg,
      i.p.) with morphine enhanced the antinociceptive effects of acute morphine.
      Repeated mibefradil administration (10 mg/kg, i.p., just before, 24 and 48 hr
      after morphine pellet implantation) completely blocked the development of
      tolerance to the antinociceptive effect of morphine and even by this effect
      reached supersensitivity to morphine. However, repeated mibefradil treatment did
      not alter the development of dependence to morphine assessed by the A(50) values
      of naloxone (s.c.) required to precipitate withdrawal jumping 72 hr after
      morphine pellet. But, acute mibefradil (10, 30, and 50 mg/kg, i.p.) dose
      dependently decreased the expression of morphine abstinence syndrome when given
      directly 30 min prior to naloxone (0,05 mg/kg, s.c.) 72 hr after morphine pellet.
      These results indicate a critical role of T-type VDCCs in morphine
      antinociception, the development of tolerance to the antinociceptive effects of
      morphine and in morphine abstinence syndrome.

PMID- 12072161
TI  - Technology transfer and the treatment of addiction: what can research offer
      practice?

PMID- 12072162
TI  - A conceptual framework for transferring research to practice.
AB  - Systematic evaluations of efforts to transfer research-based interventions and
      procedures into general practice at community drug treatment programs have been
      limited. However, practical experiences as well as results from studies of
      technology transfer and organizational behavior in related fields provide a basis
      for proposing a heuristic model of key factors that influence this process. The
      successful completion of four stages of activity typically involved in program
      change (exposure, adoption, implementation, and practice of new interventions)
      appears to be influenced by several organizational considerations (e.g.,
      institutional readiness for change, resources, and climate) as well as staff
      attributes. Assessment instruments for measuring organizational functioning
      (based on ratings aggregated for staff and patients in a program) are introduced,
      along with preliminary evidence for their validity. A better conceptual
      understanding of the process of program change and common barriers that may be
      encountered is needed for effectively transferring research to practice.

PMID- 12072163
TI  - Measuring patient attributes and engagement in treatment.
AB  - Brief but comprehensive instruments measuring patient motivation, psychosocial
      functioning, treatment process, social network support, and services received are
      needed for monitoring drug abuse treatment delivery and patient progress.
      Combining this information across patients within a program also provides useful
      indicators about institutional composition and functioning. Consequently, the
      same assessment tools can be used to identify areas where treatment protocols
      need to be changed, and to monitor improvements following such changes. The Texas
      Christian University (TCU) Client Evaluation of Self and Treatment (CEST)(1) is a
      144-item self-rating instrument that includes 16 scales measuring patient
      functioning and treatment perceptions. Psychometric properties (including
      reliability and construct validity) of the scales are examined in this article,
      based on patient samples drawn from 87 programs that participated in a series of
      staff training workshops. Acceptable reliabilities (.70 or above) were generally
      reported, and construct validity was also demonstrated (although the confirmatory
      factor analyses suggested some item pools could represent more than one factor).
      Prediction analyses were conducted using selected scales from each measurement
      domain to illustrate their sensitivity to treatment program contexts.

PMID- 12072164
TI  - Assessing organizational readiness for change.
AB  - A comprehensive assessment of organizational functioning and readiness for change
      (ORC) was developed based on a conceptual model and previous findings on
      transferring research to practice. It focuses on motivation and personality
      attributes of program leaders and staff, institutional resources, and
      organizational climate as an important first step in understanding organizational
      factors related to implementing new technologies into a program. This article
      describes the rationale and structure of the ORC and shows it has acceptable
      psychometric properties. Results of surveys of over 500 treatment personnel from
      more than 100 treatment units support its construct validity on the basis of
      agreement between management and staff on several ORC dimensions, relationships
      between staff organizational climate dimensions and patient engagement in
      treatment, and associations of agency resources and climate with organizational
      stability. Overall, these results indicate the ORC can contribute to the study of
      organizational change and technology transfer by identifying functional barriers
      involved.

PMID- 12072165
TI  - Adoption and implementation of new technologies in substance abuse treatment.
AB  - In addition to clinical outcomes, understanding the adoption and implementation
      of new treatment interventions is essential. This analysis was designed to assess
      the predictive utility of organization-level features in understanding the
      adoption and implementation of new technologies in substance abuse treatment.
      Naltrexone, which was found to be in current use in 44.1% of a national sample of
      400 private substance abuse treatment centers, was selected as an appropriate
      sample technology for study. Adoption of naltrexone is significantly related to
      both the treatment center's age and its administrative leadership. Naltrexone
      adoption is also significantly associated with the percentage of the center's
      caseload covered by managed care programs and by the percentage of relapsers
      represented in the caseload. The analysis was less successful in predicting
      naltrexone implementation for either primary alcohol dependence or primary opiate
      addiction.

PMID- 12072166
TI  - Mapping training: the transfer of a cognitive technology for improving
      counseling.
AB  - To provide information that will reduce the gap between research and practice,
      the transfer of a complex drug abuse counseling technology is examined. This
      technology, cognitive mapping, is a graphic tool shown to effectively facilitate
      communication and problem solving in group and individual counseling sessions.
      Unlike some techniques, mapping requires substantial counselor time, effort, and
      expertise to learn and to use. This article briefly describes the development and
      evolution of mapping and supporting research. It then focuses on our efforts to
      develop mapping training that will facilitate use of this evidence-based
      technique in drug abuse treatment. Major training and transfer pitfalls are
      noted, and strategies for successful training are recommended.

PMID- 12072167
TI  - Transporting a research-based adolescent drug treatment into practice.
AB  - This article describes the key ingredients and processes in transporting an
      empirically supported, research-developed family therapy for adolescent drug
      abusers, Multidimensional Family Therapy (MDFT), into an intensive day treatment
      program. Using the same systems change principles that guide this treatment
      approach, the technology transfer process has been, from its inception, a
      collaborative, multidimensional, systemic intervention aimed at changing
      organizational structures, and attitudinal and behavioral patterns with multiple
      staff members at several levels of the program. This article describes: (1) the
      conceptual and empirical basis for these technology transfer efforts; (2) the
      technology being adapted and transferred; and (3) the critical events and
      processes that have shaped the transfer of MDFT into this program. We discuss
      this process and the outcomes thus far through the lens of Simpson's
      organizational change model and specify the implications of this experience for
      the expansion of current conceptualization of technology transfer.

PMID- 12072168
TI  - The federal role in drug abuse technology transfer: a history and perspective.
AB  - The past 30 years have seen a focus on substance abuse research in association
      with the creation of federal agencies specifically mandated to guide that effort.
      While research has been well supported and largely productive, there has been
      increasing concern with the slow pace of adoption of the findings from that
      research. The history of those efforts suggests a long-standing concern with
      knowledge development, and a continuing reliance on print media to achieve
      knowledge application. Nonetheless, evidence from other human service fields, and
      increasingly from the substance abuse field, indicates interpersonal strategies
      are dramatically more effective in achieving the individual and organizational
      behavior change needed to achieve technology transfer. Argument is made that the
      federal government remains the best, if not the only resource for promoting
      technology transfer. A paradigm is described to further federal efforts in this
      area, and structural elements suggested for the achievement of technology
      transfer goals.

PMID- 12072169
TI  - A study of transcallosal inhibition in schizophrenia using transcranial magnetic
      stimulation.
AB  - A considerable body of imaging research has demonstrated morphological changes in
      the corpus callosum (CC) of patients with schizophrenia. Transcranial magnetic
      stimulation (TMS) allows the possibility for the in vivo investigation of a
      variety of aspects of brain function including the spread of information across
      the CC. We aimed to investigate whether patients with schizophrenia demonstrate
      abnormalities of transcallosal inhibition (TCI), a TMS parameter measured with
      both single and paired pulse experiments. 25 patients with DSM-IV schizophrenia
      and 20 normal volunteers participated in the study. Electromyographic (EMG)
      recordings from the bilateral abductor pollicis brevis (APB) muscle were made
      during focal TMS stimulation to the motor cortex. Experimental paradigms were
      utilised to measure both the timing and degree of the effect of TCI. The patient
      group demonstrated a reduction in the degree of TCI at rest and during a
      sustained muscle contraction. TCI commenced at the same time in the patient and
      the control group but was of prolonged duration in the patient group although the
      length of TCI correlated with medication dose. Patients with schizophrenia
      demonstrate a reduction in the degree of TCI that appeared independent of
      medication dose. The latency of TCI is not altered in the patient group
      suggesting that cortical inhibitory mechanisms, rather than corpus callosal ones,
      are likely to be the cause of these TCI alterations.

PMID- 12072170
TI  - Unirhinal olfactory identification deficits in young male patients with
      schizophrenia and related disorders: association with impaired memory function.
AB  - We have observed discreet subgroups of male patients with psychotic disorders who
      have unirhinal olfactory identification deficits (microsmia). The purpose of this
      study was to examine the relationship between left or right nostril microsmia and
      performance on literalised neuropsychological tests sensitive to lesions in brain
      areas implicated in the pathogenesis of schizophrenia. Sixty-six male patients
      diagnosed with schizophrenia or related disorders were assessed with a battery of
      neuropsychological tests, sensitive to literalised and regional (temporal and
      frontal lobe) dysfunction. The University of Pennsylvania Smell Identification
      Test (UPSIT) was administered unirhinally and resultant scores were used to
      classify patients into olfactory subgroups. Neuropsychological test scores were
      compared amongst subgroups. A mixed design MANOVA was performed on cognitive
      domains with olfactory status (right microsmic; RM, n=8, left microsmic; LM,
      n=20, and normosmic schizophrenic controls; NSzC, n=38) as the between subject
      factor while hemisphere (left versus right) and domain (executive/fluency versus
      memory) were within-subject factors. A three-way (olfactory subgroup by
      hemisphere by region) interaction was observed. Non-verbal memory impairment was
      observed in the right and left microsmic subgroups. Verbal memory deficits were
      demonstrated in patients with left nostril microsmia. These results indicate that
      unirhinal olfactory performance may provide a meaningful manner by which to
      subtype patients with schizophrenia. Moreover, the data suggest that olfactory
      deficits in patients with schizophrenia are associated with dysfunction of
      temporal lobe, rather than frontal lobe abnormalities. The data are consistent
      with reports linking the right temporal lobe integrity to adequate olfactory
      processing.

PMID- 12072171
TI  - Gaze direction determination in schizophrenia.
AB  - It has been proposed that an impairment in gaze determination is responsible for
      the paranoid symptoms reported in schizophrenia. To address this, we examined the
      gaze discrimination system in schizophrenia. Thirty-two patients suffering from
      schizophrenia (20 patients with persecutory delusions and 12 patients without
      such delusions) were compared to 32 control subjects on two specific tasks. In
      the first task, the subjects had to determine whether 130 portraits were looking
      right or left. In the second task the subjects were asked to determine whether or
      not 130 portraits were looking at them. The absolute threshold of difference used
      to investigate the influence of instruction on gaze discrimination did not show
      any difference between patients with schizophrenia, whatever paranoid or not, and
      control subjects. Paranoid patients, as well as controls, displayed a
      significantly finer discrimination threshold in the right vs. left judgment than
      in the self vs. non-self judgment. Subjects with schizophrenia were able to
      discriminate gaze direction in the two tasks, but they took significantly more
      time in the task requiring to determine the presence or the absence of a mutual
      gaze contact than in the other one, whereas controls took the same duration to
      elicit both tasks. These data are consistent with those reporting that perceptual
      abilities are spared in schizophrenia while delusions are related to an
      impairment of a higher level of analysis.

PMID- 12072172
TI  - Soluble interleukin 2 receptor levels in families of people with schizophrenia.
AB  - BACKGROUND: Several authors have reported increased soluble interleukin 2
      receptor (sIL2Ralpha) concentrations in schizophrenia. The aim of this work was
      to examine serum sIL2Ralpha in the first degree relatives of patients with
      schizophrenia. METHODS: We sampled 51 first degree relatives of patients with DSM
      IIIR schizophrenia. These relatives were unaffected by psychosis and included
      nine fathers, thirteen mothers, seventeen sisters and twelve brothers. They were
      compared to 126 controls who were not pregnant, had no known autoimmune disorder
      and no intercurrent illness. Neither the controls, nor their first degree
      relatives, suffered from a psychotic illness. Serum sIL2Ralpha was analysed using
      a commercial ELISA preparation (Quantikine sIL2Ralpha immunoassay - R and D
      Systems, Inc.). We used non-parametric Mann Whitney U test and Spearman
      correlation throughout. SIL2Ralpha levels were adjusted for higher levels in
      females and with increasing age. RESULTS: Adjusted mean sIL2Ralpha values of
      unaffected siblings, averaged within their families, were higher than controls
      (n=14, one-tailed p=0.027). There was no difference in sIL2Ralpha values between
      fathers or mothers and controls following regression for age and sex. CONCLUSION:
      Soluble interleukin 2 receptoralpha levels are increased in siblings of patients
      with schizophrenia.

PMID- 12072173
TI  - Hydrocortisone induced regional cerebral activity changes in schizophrenia: a PET
      scan study.
AB  - BACKGROUND: There is evidence that, even during remission, schizophrenia (SZ)
      patients are especially vulnerable to de-compensate under stress, and that they
      tend to have a high baseline serum cortisol levels. This study was undertaken to
      determine whether raising serum cortisol by the infusion of hydrocortisone, in
      the absence of additional psychological stress, would result in different
      cerebral activity changes in schizophrenic patients compared to normal controls
      (CON). We were especially interested in cerebral activity in regions such as the
      medial temporal lobe and hippocampus, since structural abnormalities in these
      brain regions were frequent in association with schizophrenia. METHODS: Serum
      cortisol levels were raised, by infusing hydrocortisone, in 8 pairwise-matched SZ
      patients and 8 CONs. The associated regional cerebral activity changes were
      analyzed using statistical parametric mapping (SPM). RESULTS: There was increased
      regional cerebral activity in response to elevated cortisol in the left
      hippocampal region in the SZ group, while the controls showed evidence of
      decreased regional cerebral activity in the same anatomical location. For the
      rest of the brain regions, cerebral activity increases and decreases, in response
      to raised serum cortisol, in the SZ followed the same regional pattern as in the
      control group, but with a smaller overall magnitude of change. The blunted
      response in SZ was most marked in the regions that showed greatest regional
      cerebral activity changes in normal subjects. CONCLUSION: Patients with
      schizophrenia showed an abnormal increased regional cerebral activity response to
      cortisol infusion in the left hippocampal region, and similar but attenuated
      regional cerebral activity response in other regions, when compared to matched
      controls.

PMID- 12072175
TI  - Cell death during development.
AB  - There are many ways to measure apoptosis and other forms of programmed cell death
      in development. Once nonmammalian embryos have passed the midblastula transition,
      or much earlier in mammalian embryos, apoptosis is similar to that seen in adult
      organisms, and is used to sculpt the animal, fuse bilateral tissues, and
      establish the structure of the nervous system and the immune system. Embryos
      present unique problems in that, in naturally occurring cell deaths, few cells
      are involved and they are frequently in very restricted regions. Thus,
      identification of apoptotic or other dying cells is more effectively achieved by
      microscopy-based techniques than by electrophoretic or cell-sorting techniques.
      Since embryos have many mitotic cells and are frequently more difficult to fix
      than adult tissues, it is best to confirm interpretations by the use of two or
      more independent techniques. Although natural embryonic deaths are frequently
      programmed and require protein synthesis, activation of a cell death pathway is
      often post-translational and assays for transcriptional or translational changes
      as opposed to changes in aggregation of death-related molecules or proteolytic
      activation of enzymes-is likely to be uninformative. Also, embryos can frequently
      exploit partially redundant pathways, such that the phenotype of a knockout or
      upregulated death-related gene is often rather modest, even though the adult may
      develop response or regulation problems. For these reasons, the study of cell
      death in embryos is fascinating but researchers should be cautious in their
      analyses.

PMID- 12072176
TI  - Death to flies: Drosophila as a model system to study programmed cell death.
AB  - Programmed cell death (PCD) is essential for the removal of unwanted cells and is
      critical for both restricting cell numbers and for tissue patterning during
      development. Components of the cell death machinery are remarkably conserved
      through evolution, from worms to mammals. Central to the PCD process is the
      family of cysteine proteases, known as caspases, which are activated by death
      inducing signals. Comparisons between C. elegans and mammalian PCD have shown
      that there is additional complexity in the regulation of PCD in mammals. The
      fruitfly, Drosophila melanogaster, is proving an ideal genetically tractable
      model organism, of intermediary complexity between C. elegans and mammals, in
      which to study the intricacies of PCD. Here, we review the literature on PCD
      during Drosophila development, highlighting the methods used in these studies.

PMID- 12072177
TI  - Quantitation of mitochondrial alterations associated with apoptosis.
AB  - Mitochondria undergo two major changes during early apoptosis. On the one hand,
      the outer mitochondrial membrane becomes permeable to proteins, resulting in the
      release of soluble intermembrane proteins (SIMPs) from the mitochondrion. On the
      other hand, the inner mitochondrial membrane transmembrane potential
      (DeltaPsi(m)) is reduced. These changes occur in most, if not all, models of cell
      death and can be taken advantage of to detect apoptosis at an early stage. Here,
      we delineate methods for the detection of alterations in the DeltaPsi(m), based
      on the incubation of cells with cationic lipophilic fluorochromes, the uptake of
      which is driven by the DeltaPsi(m). Certain DeltaPsi(m)-sensitive dyes can be
      combined with other fluorochromes to detect simultaneously cellular viability,
      plasma membrane exposure of phosphatidylserine residues, or the mitochondrial
      production of reactive oxygen species (ROS). In addition, we describe an
      immunofluorescence method for the detection of two functionally important
      proteins translocating from mitochondria, namely, the caspase co-activator
      cytochrome c and the caspase-independent death effector apoptosis inducing factor
      (AIF).

PMID- 12072178
TI  - Regulation and measurement of oxidative stress in apoptosis.
AB  - Cells are constantly generating reactive oxygen species (ROS) during aerobic
      metabolism. As a consequence, each cell is equipped with an extensive antioxidant
      defence system to combat excessive production of ROS. Oxidative stress occurs in
      cells when the generation of ROS overwhelms the cell's natural antioxidant
      defences. There is a growing consensus that oxidative stress and the redox state
      of a cell plays a pivotal role in regulating apoptosis, a tightly controlled form
      of cell death in which a cell partakes in its own demise. More recently, a role
      for reactive nitrogen species (RNI) as both positive and negative regulators of
      cell death has been established. This review describes the major sources of ROS
      and RNI in a cell, the control of cell death by these species and the role of
      antioxidants as regulators of oxidative stress and apoptosis. Finally, the
      various methods that can be employed in establishing a role for both ROS and RNI
      in apoptosis will be discussed with particular emphasis on their intracellular
      detection.

PMID- 12072179
TI  - Investigating the relationship between the cell cycle and apoptosis using flow
      cytometry.
AB  - Methods for using flow cytometry to investigate the relationship between the
      induction of apoptosis and the cell cycle are discussed. Methods for following
      cell cycle progression are also briefly reviewed. The methods are illustrated
      using a specific example of the effect of withdrawing an essential growth factor
      from a cell line.

PMID- 12072180
TI  - Multiparametric flow cytometric analysis of biochemical and functional events
      associated with apoptosis and oncosis using the 7-aminoactinomycin D assay.
AB  - Apoptosis and primary necrosis are the two modes of cell death induced by a
      lethal injury. The majority of structural and biochemical events occurring during
      cell death can be analysed by flow cytometry. The 7-aminoactinomycin D (7-AAD)
      assay can be used to detect the loss of membrane integrity during apoptosis of
      murine thymocytes and human peripheral lymphocytes. We describe here new
      applications of the 7-AAD assay. It can be applied to a variety of cell lines of
      different origins, including adherent cell lines, and it allows the co-detection
      of lipidic antigens such as phosphatidylserine (PS) residues, and biochemical
      processes linked to apoptosis, such as the loss of mitochondrial transmembrane
      potential, cardiolipin peroxidation, the expression of the 7A6 mitochondrial
      antigen and DNA fragmentation. Thus, this assay is a noninvasive method
      particularly adapted to the analysis of biochemical events associated with cell
      death. Finally, we show that this assay is not specific for apoptosis since it
      detects oncosis, the early stage of primary necrosis.

PMID- 12072181
TI  - Evaluation of caspase activity in apoptotic cells.
AB  - A family of cysteine proteases, the caspases, plays a central role in the
      initiation and execution phases of apoptosis. Upon activation, these enzymes
      cleave specific substrates and thereby mediate many of the typical biochemical
      and morphological changes in apoptotic cells, such as cell shrinkage, chromatin
      condensation, DNA fragmentation and plasma membrane blebbing. Hence, the
      detection of activated caspases can be used as a biochemical marker for
      apoptosis. Here we review a set of methods available for characterizing and
      quantifying the activation of caspases, including immunoblotting, cleavage of
      synthetic substrates, affinity labeling and confocal microscopy. Each method is
      described in general terms and the advantages and disadvantages of each technique
      are discussed.

PMID- 12072182
TI  - Assay of caspase activation in situ combined with probing plasma membrane
      integrity to detect three distinct stages of apoptosis.
AB  - Activation of cysteine-aspartic acid specific proteases (caspases) in situ, in
      live cells, can be detected using fluorochrome-labeled inhibitors of caspases
      (FLICA), the reagents that covalently bind to the active center of these enzymes.
      In the present study, this assay was combined with a probe of plasma membrane
      capacity to exclude the cationic fluorochrome propidium iodide (PI). Apoptosis of
      HL-60 cells was induced by DNA topoisomerase I inhibitor camptothecin (CPT). The
      cells were then incubated with FAM-VAD-fluoro-methyl ketone (FMK), the pan
      caspase FLICA, and subsequently briefly exposed to PI. The intensity of cellular
      green fluorescence of FLICA and red fluorescence of PI was measured by laser
      scanning cytometry (LSC) as well as by flow cytometry. Four distinct
      subpopulations were distinguished based on differences in fluorescence intensity.
      The subpopulations represented the sequential transitions from the stage when (a)
      the cells were both FLICA and PI negative (FLICA-/PI-), through the stages when
      (b) their caspases become progressively activated (FLICA+/PI-), (c) when their
      plasma membrane ability to exclude PI was lost (FLICA+/PI+), and finally (d) when
      the cell propensity to bind FLICA was eliminated (FLICA-/PI+). By estimating the
      percentage of cells in each subpopulation at different time points after
      administration of CPT, it was possible to study the kinetics of the transitions.
      The cell entry to-and progression through-these substages was asynchronous.
      Following this "supravital" analysis, the cells may be fixed, permeabilized,
      their DNA stoichiometrically stained with PI and cell cycle distribution of each
      of the four subpopulations analyzed. The loss of cells' ability to bind FLICA at
      the late stage of apoptosis indicates that caspases are either inactivated,
      degraded or excreted at that time point. Hence, the late apoptotic cells may not
      be identified solely on the evidence of the presence of activated caspases. The
      direct transition from FLICA-/PI- to FLICA-/PI+, bypassing the FLICA+ stages, may
      be considered as the marker of a primary cell necrosis.

PMID- 12072183
TI  - Visualization of cell death in vivo with the annexin A5 imaging protocol.
AB  - Annexin A5 binds to phosphatidylserine (PS), which is one of the "eat me" signals
      at the surface of the apoptotic cell. This property has been the driving force
      for the research of annexin A5 as a probe to measure apoptosis in vitro and in
      vivo. A non-invasive imaging protocol using annexin A5 has been developed and
      applied successfully to measure programmed cell death programmed cell death (PCD)
      in patients. This review highlights the aspects of this development and discusses
      clinical relevance, limitations and future perspectives of this approach of
      visualizing cell death.

PMID- 12072184
TI  - Flow cytometric approach to the study of erythrophagocytosis: evidence for an
      alternative immunoglobulin-independent pathway in agammaglobulinemic mice.
AB  - Neuraminidase treatment of red blood cells (RBCs) is believed to induce changes
      similar to RBC senescence, and leads to a rapid clearance of RBCs from the
      circulation in vivo. The objective of this study using immunodeficient SCID mice
      and the lipophilic fluorescent probe PKH-26 was to ascertain whether antibodies
      are required as the final signal allowing the phagocytosis of neuraminidase
      treated murine RBCs. All of the methods we applied are based on flow cytometry
      analysis using fluorescent probes: fluoresceinyl isothiocyanate (FITC)-labeled
      lectins for membrane carbohydrate identification and PKH-26-labeled RBCs for in
      vitro phagocytosis and in vivo clearance studies. The results can be summarized
      as follows: (i) the rate of neuraminidase-induced desialylation of RBCs from
      normal and immunodeficient mice is identical as ascertained with FITC-labeled
      lectins (wheat germ agglutinin (WGA) and Ricinus communis agglutinin (RCA(120)));
      (ii) the rate of clearance of enzyme-treated RBCs from both types of mice is also
      similar, as is their localization in spleen, liver and lung; (iii) the rates of
      in vitro phagocytosis of untreated and neuraminidase-treated PKH-26-labeled RBCs
      from both species of mice are very similar in the presence of homologous sera. In
      the absence of serum or in the presence of heterologous sera, the rate of
      phagocytosis is markedly decreased but not totally abolished. These data suggest
      that neuraminidase-treated RBCs can be cleared via an alternative pathway that is
      antibody-independent. This pathway exists in immunocompetent mice but with a very
      low activity and is the only one active in immunodeficient mice. In accordance
      with results reported by Connor et al. [J. Biol. Chem. 269 (1994) 2399], it is
      possible that this antibody-independent mechanism is involved in the clearance of
      circulating senescent RBCs. Finally, the methods described here may also be of
      interest for the investigation of the mechanisms involved in the phagocytosis of
      apoptotic cells.

PMID- 12072185
TI  - "Tissue" transglutaminase in AIDS.
AB  - Apoptosis or programmed cell death (PCD) is an active process of cellular self
      destruction, essential for embryonic development and maintenance of homeostasis
      of multicellular organisms. Programmed cell death induction can serve as a
      defence mechanism of the host against intracellular microbes. Virus infections
      trigger host cell apoptosis, which can either limit virus production or
      contribute directly to viral pathogenesis. Several independent laboratories have
      identified "tissue" transglutaminase (tTG) as a potentially important player of
      the cell death program(s). This gene is specifically expressed in cells dying
      during mammalian development as well as in those undergoing apoptosis in various
      patho-physiological and experimental settings [Eur. J. Cell Biol. 56 (1991) 170;
      Piacentini, M., Davies, P.J.A., Fesus, L., 1994. Tissue transglutaminase in cells
      undergoing apoptosis. In: Tomei, L.D., Cope, F.O. (Eds.), Apoptosis II: The
      molecular basis of apoptosis in disease. Cold Spring Harbor Lab. Press, pp. 143
      165.]. This chapter reviews recent studies concerning the expression and the
      possible role of "tissue" transglutaminase (tTG) in apoptotic cells; particular
      emphasis is given to its expression in the cell death pathways associated with
      HIV infection in the immune system. We propose here that the induction of the tTG
      gene in cells of the immune system, as well as the detection of the isodipeptide
      epsilon(gamma-glutamyl)lysine in plasma, are useful markers of apoptosis and
      might make it possible to monitor disease progression in HIV-infected
      individuals.

PMID- 12072186
TI  - Methods for detecting apoptosis in thyroid diseases.
AB  - Over the last few years, the importance of apoptosis in determining the fate of
      thyrocytes in autoimmune thyroid disease has been the topic of intense
      investigation. It is now clear that thyrocytes from patients with Hashimoto's
      thyroiditis are destroyed as a result of an apoptotic process. However, there is
      no general consensus on whether the intrathyroidal lymphocytes or the thyrocytes
      themselves are responsible for their death. The use of a wide range of techniques
      has contributed to the assessment of this process both in situ on thyroid
      sections and in vitro on thyroid cell preparations. The apoptosis field of
      research is rapidly evolving and as the pathways to cell death become unravelled,
      novel methods will emerge. As each technique offers some advantage, it is
      critical to know the most suitable method for a specific study. Equally, each
      method also has intrinsic limitations. Thus, to achieve reliable results, it is
      necessary to use more than one technique per study. In addition, techniques
      related to the measurement of the expression of pro-apoptotic and anti-apoptotic
      genes have been contributing to the study of the susceptibility of the cells to
      apoptosis and/or to their ability to kill themselves or neighbouring cells. In
      this review we will focus on the most relevant techniques.

PMID- 12072187
TI  - Dendritic cells crossprime allo-specific self-restricted CD4(+) T cells after
      coculture with dead allogeneic cells.
AB  - Indirect alloreactivity, i.e., the recognition of allopeptides on self-MHC
      molecules, contributes both to acute and chronic rejection of transplants. The
      antigen presenting cell priming these allo-specific self-restricted T cells is
      unknown. We demontrate that dendritic cells, which have been matured in the
      presence of necrotic allogeneic cells, can crossprime allo-specific self
      restricted CD4(+) T cells in vitro. We demonstrate dendrtitic cell mediated
      crosspriming of HLA-DR13 specific, HLA-DR7 restricted and HLA-DR1 specific, HLA
      DR11 restricted CD4(+) T cells. The allo-specific self-restricted CD4(+) T cells
      primed in our culture system secrete predominantly Th1 and not Th2 cytokines. The
      use of dendritic cells to monitor the indirect pathway of alloreactivity should
      help to design and understand interventions against acute and chronic transplant
      rejection.

PMID- 12072188
TI  - Diltiazem impairs maturation and functions of human dendritic cells.
AB  - The aim of this study was to define the effects of diltiazem, a calcium
      antagonist drug used in cardiology and in clinical transplantation, on the
      differentiation and maturation of human dendritic cells (DC). Herein, we
      demonstrate that diltiazem, in association with granulocyte macrophage-colony
      stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to
      differentiate into cells with many of the characteristic of DC. However,
      diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII
      and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4
      induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to
      lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12
      and reveal a reduced ability to stimulate alloreactive T-cell responses as well
      as in inducing interferon-gamma producing Th1 cells. These effects may contribute
      to a decreased DC-dependent T-cell activation and may help to explain the
      immunoregulatory function of diltiazem and its effectiveness in preventing
      transplant rejection.

PMID- 12072189
TI  - Surface density expression of the leukocyte-associated Ig-like receptor-1 is
      directly related to inhibition of human T-cell functions.
AB  - The relevance of inhibitory receptors that downregulate T-cell functions, such as
      CD152 (CTLA-4) and CD85j, have been extensively analyzed. This study will show
      that leukocyte-associated Ig-like receptor-1 (LAIR-1) acts as an inhibitory
      receptor for antigen-specific human effector T cells. To this end 28 CD8(+) and
      22 CD4(+) T-cell clones were analyzed. LAIR-1 activity appears to be clonally
      distributed among T-cell clones and inhibition of T lymphocyte functions ranges
      from 4% to 49% in a redirected killing assay. This inhibitory function, although
      less efficient than that exerted by other inhibitory receptors expressed by T
      cells (i.e., CD152 and CD85j), downregulates the cytotoxic activity of CD8(+) T
      lymphocytes, both in a CD3-mediated and in an antigen-specific system.
      Furthermore, LAIR-1 inhibits the proliferative response of CD4(+) T lymphocytes
      to recall antigens and in CD3 stimulation. LAIR-1 also modulates cytokine
      production, downregulating IL-2 and IFN-gamma production. In contrast, LAIR-1
      crosslinking induces secretion of transforming growth factor beta. This study
      will also demonstrate that a direct relationship exists between surface density
      expression of LAIR-1 molecules and their ability to modulate CD3-mediated
      activation of both CD8(+) and CD4(+) T-cell clones.

PMID- 12072190
TI  - Clonal diversity of the T-cell population responding to a dominant HLA-A2 epitope
      of HER-2/neu after active immunization in an ovarian cancer patient.
AB  - Natural antigen processing and presentation of antigen is thought to be important
      for the generation of a broad functional repertoire of antigen-specific T cells.
      In this study, the T-cell repertoire to an immunodominant human leukocyte antigen
      A2 (HLA-A2) binding peptide epitope of HER-2/neu, p369-377, was examined in a
      patient following immunization with a peptide-based vaccine consisting of helper
      peptides encompassing HLA-A2 peptide epitopes. The responding T-cell repertoire
      generated was both phenotypically and functionally diverse. A total of 21 p369
      377 clones were generated from this patient. With the exception of two clones,
      all clones were CD3(+). Sixteen of the clones were CD8(+)/CD4(-). Five of the
      clones were CD4(+)/CD8(-), despite being generated with an HLA-A2 binding
      peptide. Nineteen of 21 of clones expressed the alpha beta-T-cell receptor (TCR).
      The remaining two clones expressed the gamma delta T-cell response (TCR).
      Selected alpha beta-TCR clones, both CD8(+) and CD4(+), could lyse HLA-A2
      transfected HER2 overexpressing tumor cells and p369-377-loaded B-lymphoblastic
      cell line. In addition to their lytic capabilities these clones could be induced
      to produce interferon-gamma (IFN-gamma) specifically in response to p369-377
      peptide stimulation. The 2 gamma delta-TCR clones expressed CD8 and lysed HLA
      A2(+) HER-2/neu(+) tumor cells, but not HLA-A2(-) HER-2/neu(+) tumor cells. One
      of gamma delta-TCR clones also released IFN-gamma directly in response to p369
      377 stimulation. These results suggest that a tumor antigen TCR, directed against
      a specific epitope, can be markedly polyclonal at multiple levels including
      CD4/CD8 and TCR.

PMID- 12072191
TI  - T-cell clonotypes specific for Dermatophagoides pteronyssinus in the skin lesions
      of patients with atopic dermatitis.
AB  - T-cell mediated immune response, toward the house dust mite (HDM) antigens in
      particular, has been reported to be involved in the pathogenesis of atopic
      dermatitis (AD). On the other hand, studies on the infiltrating lymphocytes in
      the skin lesion of AD revealed oligoclonal T-cell accumulation. However, it is
      not clear exactly what antigen(s) the accumulating T cells are exactly recognize
      in situ. Therefore, this study attempted to determine whether or not the clonally
      expanded T-cell clones in the diseased skin recognize HDM. Specifically,
      peripheral blood mononuclear cells (PBMC) obtained from six patients with AD, who
      revealed high titers of anti-HDM IgE, were stimulated with HDM antigens purified
      from Dermatophagoides pteronyssinus (Dp). T-cell clonotypes expanded by the
      stimulation were then identified by the analysis of their T-cell receptor (TCR) B
      gene sequences using a combination of the reverse transcription-polymerase chain
      reaction and subsequent single strand conformation polymorphism separation. The
      Dp-responding T-cell clonotypes were compared with those that accumulated in the
      AD skin lesion in vivo. Nucleotide sequences of the TCR were also determined. As
      a result, the Dp stimulation induced oligoclonal T-cell expansion from the
      originally heterogeneous peripheral T-cell population of AD patients. However,
      only a small part of the Dp-reacting T-cell clonotypes detected in PBMC was
      identical to those accumulated in the AD skin lesion in vivo, and vice versa.
      This indicates that the frequency of the clonal expansion of Dp-specific T-cell
      clonotypes in the skin lesion of AD would be rather limited.

PMID- 12072192
TI  - Functional and phenotypic properties of peripheral T cells anergized by
      autologous CD3(+) depleted bone marrow cells.
AB  - We have previously demonstrated that bone marrow cells (BMC) inhibit the
      generation of autologous Epstein-Barr virus (EBV) -specific cytotoxic T
      lymphocytes (CTL). It was also observed that CD3(+) cells obtained after 7 days
      of culture in the presence of autologous BMC could be used as inhibitors of EBV
      CTL generation. In the present study, we examined these BMC induced regulator
      CD3(+) T cells with respect to phenotype, function, and T-cell activation
      pathways. We also questioned if the CD3(+) regulatory cell function is mediated
      by their direct effect on peripheral T cells or on the ability of antigen
      presenting cells (APC) to stimulate peripheral T cells. To answer this, CD3(+)
      cells from peripheral blood lymphocytes (PBL) were cultured with either CD3
      depleted BMC or with CD3-depleted PBL. The CD3(+) cells were then isolated with
      immunomagnetic beads, designated as T(BM) and T(PBL), and were compared in
      functional studies. There was an increase in the expression of CD25 on T(BM)
      cells. The T(BM) cells also expressed less CD122 and a decreased number of CD3
      molecules per cell. Both T(BM) and T(PBL) cell populations responded to mitogen
      (PHA) to the same magnitude. However, when stimulated through the CD3 complex
      with anti-CD3 monoclonal antibody (mAb), the T(BM) cells had a significantly
      decreased response than did T(PBL). The addition of IL-2 to these latter cultures
      augmented, but could not fully restore, the response. Additionally, stimulation
      of T(BM) cells with allogeneic cells failed to produce cytotoxic T cells. These
      "anergized" T(BM) and "nonanergized" (control) T(PBL) cells were added as third
      party cells to a CTL generating culture of autologous PBL stimulated with
      allogeneic cells. The T(BM) cells exhibited suppressor function and inhibited the
      generation of CTL, in contrast with T(PBL). The effect of T(BM) cells on direct
      and indirect antigen presentation pathways demonstrated that T(BM) primarily
      effected indirect, but not direct, alloantigen presentation. To further explore
      the cytoplasmic T-cell activation events that occurred after the coculture of the
      PBL T cells with BMC, the levels of zeta-associated protein 70 (ZAP70) and
      extracellular receptor-activated kinase (ERK) were determined. There was a
      decrease in ZAP70 levels in the T(BM), which correlated with its reduced
      expression of cell surface CD3 and the attenuated response to anti-CD3 mAb
      activation. However, the activity of ERK was equally expressed by T(BM) and
      T(PBL). It, therefore, appears that the culturing of peripheral T cells with (non
      T) BMC anergizes these cells (which become refractory to stimulation through the
      T-cell receptors), and induces immune suppressor function. These in vitro
      observations may provide a mechanism by which infused donor BMC serve to
      downregulate T-cell immunity.

PMID- 12072193
TI  - CM1 ligation initiates apoptosis in a caspase 8-dependent manner in Ramos cells
      and in a mitochondria-controlled manner in Raji cells.
AB  - Burkitt lymphoma (BL) is a tumor with the characteristics of germinal center B
      cells. We previously reported that the CM1 (centrocyte/-blast marker 1) molecule
      is expressed only in germinal center B cells, specifically, in a subpopulation of
      centroblasts and centrocytes. In the present study, we investigated the apoptosis
      induced by anti-CM1 in the Ramos and Raji human BL cell lines. The Ramos is
      protected from apoptosis by the crosslinking of sIgM and the calcium ionophore by
      the ligation of CD40 with anti-CD40 monoclonal antibodies (mAb) or soluble CD40
      ligand (sCD40L). In this investigation on the effect of CM1 on apoptosis in BL
      cell lines, we found that cellular signaling by CM1 induces apoptosis and
      decreases cell viability, in BL cell lines cultured for 24 hours with protein-G
      agarose beads conjugated anti-CM1 mAb. Stimulation by CD40 ligated with sCD40L
      protected Raji cells from CM1-induced apoptosis, but did not protect Ramos cells.
      Furthermore, after anti-CM1 mAb stimulation, CD95 expression was upregulated and
      CD40 expression was unaltered or slightly decreased in Ramos cells, whereas CD95
      was downregulated and CD40 was slightly upregulated in Raji cells. The engagement
      of CD40 by sCD40L enhanced CD95 expression, but the level of CM1 expression was
      unchanged in Ramos. However, sCD40L downregulated both CD95 and CM1 expression in
      Raji. In addition, the caspase-8 specific inhibitor blocked CM1-induced apoptosis
      in Ramos cells, but not in Raji cells. Increased mitochondrial membrane
      permeabilization was observed only in Raji cells. Moreover, the effector caspase
      inhibitor, z-DEVD, blocked CM1-mediated apoptosis in both cell lines. We found
      that CM1-induced apoptosis is achieved via different initiation pathways, which
      are cell-type dependent.

PMID- 12072194
TI  - Leucine-rich repeats of the class II transactivator control its rate of nuclear
      accumulation.
AB  - Activation of class II major histocompatibility complex (MHC) gene expression is
      regulated by a master regulator, class II transcriptional activator (CIITA).
      Transactivation by CIITA requires its nuclear import. This study will address a
      mechanistic role for the leucine-rich repeats (LRR) of CIITA in regulating
      nuclear translocation by mutating 12 individual consensus-motif "leucine"
      residues in both its alpha-motifs and beta-motifs. While some leucine mutations
      in the LRR motif of CIITA cause congruent loss of transactivation function and
      nuclear import, other alanine substitutions in both the alpha-helices and the
      beta-sheets have normal transactivation function but a loss of nuclear
      accumulation (i.e., functional mutants). This seeming paradox is resolved by the
      observations that nuclear accumulation of these functional mutants does occur but
      is significantly less than wild-type. This difference is revealed only in the
      presence of leptomycin B and actinomycin D, which permit examination of nuclear
      accumulation unencumbered by nuclear export and new CIITA synthesis. Further
      analysis of these mutants reveals that at limiting concentrations of CIITA, a
      dramatic difference in transactivation function between mutants and wild-type
      CIITA is easily detected, in agreement with their lowered nuclear accumulation.
      These experiments reveal an interesting aspect of LRR in controlling the amount
      of nuclear accumulation.

PMID- 12072195
TI  - Molecular diversity of the HLA-C gene identified in a caucasian population.
AB  - A DNA typing procedure, based on a two stage polymerase chain reaction-sequence
      specific oligonucleotide probe (PCR-SSOP) typing strategy, has been developed and
      applied to DNA from 1000 healthy individuals from the Northern Ireland region.
      The two-stage procedure involves human leukocyte antigen (HLA-C) identification
      through the use of a medium resolution PCR-SSOP system, followed by four
      secondary group specific PCR-SSOP systems, to enable allele resolution. The PCR
      SSOP systems were designed for the identification of HLA-Cw alleles with possible
      discrimination within exons 2 and 3 of the HLA-C gene, i.e., HLA-Cw*01-Cw*16. PCR
      SSP tests were designed for the resolution of HLA-Cw*17 and -Cw*18 alleles. The
      systems can also be used independently of each other if selective allele
      resolution is required. HLA-Cw allele frequencies occurring within the Northern
      Ireland population have been compiled, along with estimations of HLA-B/Cw
      haplotype frequencies.

PMID- 12072196
TI  - HLA antigens, alleles and haplotypes among the Yup'ik Alaska natives: report of
      the ASHI Minority Workshops, Part II.
AB  - As part of the American Society for Histocompatibility and Immunogenetics
      coordinated studies among minority populations, human leukocyte antigen (HLA)
      alleles were defined for 460 volunteer Yup'ik Eskimos from the Yukon Kuskokwim
      delta region of southwestern Alaska. The study group included 252 adults with no
      other first-degree relatives and 48 informative nuclear families. Full Yupik
      ancestry through both maternal and paternal grandparents was claimed by 81.1% of
      participants. HLA-A, -B, -Cw, -DRB1, and -DQB1 alleles were determined by SBT,
      SSOP, reverse SSOP, and/or RSCA according to the protocols of five participating
      laboratories. Polymorphism was limited with 3-6 alleles comprising > 80% of the
      alleles observed at each locus. Homozygosity was high, particularly at the HLA-A
      and -DQB1 loci, with 36.6% and 44% of individuals having a single allele defined
      at these respective loci. HLA-A, -B, and -DRB1 alleles were in Hardy-Weinberg
      equilibrium, whereas HLA-Cw and -DQB1 alleles gave significant deviation (p =
      0.002; 0.005). Significant linkage disequilibrium (p < or = 0.00001) was observed
      in all pairwise evaluations. A new Cw*0806 allele was observed in high linkage
      disequilibrium with B*4801(Delta = 0.099; Delta(rel) = 1.0). Three extended
      haplotypes were found to have frequencies > 5%, the most prevalent being A*2402;
      B*4801; DRB1*0401; DQB1*0301 (0.0933). Comparison of available class I data
      indicate that the Yup'ik share several common alleles with other Native American
      populations, including: A*2402, *0206, *6801; B*1501, *2705, *3501, *4002, *4801,
      *5101; and Cw*0202, *0304, *0401. Comparisons of class II data also confirm a
      close relationship of the Yup'ik to two other Eskimo populations, Siberian and
      East Greenland Eskimos. DRB1*0401 and *1101, which occur in high frequency among
      these Eskimo populations, but not in other Native Americans, were also prevalent
      among the Yup'ik, with respective frequencies of 0.232 and 0.107.

PMID- 12072198
TI  - Updates on the cytogenetics and molecular genetics of bone and soft tissue
      tumors. gastrointestinal stromal tumors.

PMID- 12072199
TI  - Application of multiplex fluorescence in situ hybridization in the cytogenetic
      analysis of primary gastric carcinoma.
AB  - The different genetic alterations observed in diffuse and intestinal types of
      gastric cancer suggest that these two pathological types may represent different
      disease entities. We present two cases of primary gastric carcinoma, a well
      differentiated intestinal type adenocarcinoma and a poorly differentiated diffuse
      type adenocarcinoma, both studied by a 24-color multiplex fluorescence in situ
      hybridization technique (M-FISH). The well-differentiated intestinal type
      adenocarcinoma exhibited fewer structural abnormalities with five noncomplex
      translocations, deletions of chromosomes 5q, 6q, and 17q and an i(8q). In the
      case of poorly differentiated diffuse carcinoma, structural abnormalities
      predominated and normal homologues were mostly absent. But there were also
      similarities between the two cases: translocations on 1p and 9p; structural
      abnormalities of chromosome 8 with consistent loss of 8p; structural
      abnormalities of 12q; partial loss of chromosome 17 and 18; and polysomy of
      chromosome 20. This study shows that M-FISH is valuable in identifying hidden
      structural abnormalities and could, therefore, be useful in the investigation of
      primary solid tumors.

PMID- 12072200
TI  - Interpretation of the complex karyotype and identification of a new 6p amplicon
      by integrated comparative genomic hybridization and fluorescence in situ
      hybridization on the U937-I cell line.
AB  - Molecular cytogenetics is helpful to identify complex and cryptic genomic changes
      in malignancy. Human leukemic cell lines are an important tool for advancements
      of biological research on malignant cells, one critical step being
      characterization of genomic changes. We used fluorescence in situ hybridization
      and comparative genomic hybridization to refine karyotypic interpretation of the
      diffuse histiocytic lymphoma derived U937-1 cell line. From this integrated
      approach, chromosome material involved in nine karyotypic markers and in
      unbalanced translocations could be identified. Moreover, a previously undetected
      amplicon emerged within band 6p21. The U937-I is a new in vitro model to study
      genome amplification and unknown recombinations in leukemic cells, such as those
      involving the centromeric region of chromosome 1.

PMID- 12072201
TI  - Spectrum of genetic changes in gastro-esophageal cancer cell lines determined by
      an integrated molecular cytogenetic approach.
AB  - Adenocarcinomas arising around the gastro-esophageal junction (GEJ) are highly
      malignant, and their incidence has risen rapidly in the last decades. Cell lines
      are the basic in vitro system for functional and therapeutic studies in GEJ
      tumors, but only a small number of cell lines are currently available, and none
      of them has been fully karyotyped. We analyzed 5 GEJ tumor cell lines using a
      combination of 24-color fluorescence in situ hybridization (FISH), comparative
      genomic hybridization (CGH) and genomic microarrays. Using CGH we demonstrated
      that these cell lines present imbalances similar to those we had previously
      observed in primary GEJ tumors, namely gains on 1q, 7q, 8q, 17q, 19q, 20, and X,
      and losses on 3p, 4, 5q, 9p, 18q, and 21. Multicolor FISH karyotyping revealed
      multiple structural rearrangements involving chromosomes 1, 5, 6, 7, 8, 9, 13,
      17, 18, and 22. Rearrangements of chromosome 8 involved 10 different chromosomes,
      while rearrangements of chromosome 17 involved 5. Different rearrangements
      resulted in imbalances of similar chromosome regions, suggesting that similar
      genomic imbalances are constitutively important but are achieved through
      different pathways. The use of a commercially available genomic array excluded
      TOP2A (17q), and MYBL2, PTPT1, CSE1L, and ZNF217 (20q) as candidate genes for
      frequently amplified areas on these chromosomes, and contributed to refining the
      limits of chromosome regions involved in genomic imbalances.

PMID- 12072202
TI  - Two regions of deletion in 9p22- p24 in neuroblastoma are frequently observed in
      favorable tumors.
AB  - Neuroblastoma is a tumor of infancy that presents several chromosomal
      abnormalities. Nonrandom deletion of chromosome arm 9p has been identified in
      primary neuroblastoma suggesting the presence of a tumor suppressor gene located
      on this chromosome. In previous work, we showed that CDKN2A and CDKN2B genes,
      mapped at 9p21, were not deleted in neuroblastoma cells. In the present article,
      we refine the deleted region of 9p using polymerase chain reaction-based analysis
      of highly polymorphic simple sequence repeats and a two color fluorescence in
      situ hybridization technique on interphase nuclei. We analyzed 71 primary tumors
      of patients at the onset of the disease. We found loss of heterozygosity (LOH) in
      16 of 71 (23%) cases; the frequency of LOH for 9p was higher (28%) in favorable
      stages 1, 2, and 4s than in unfavorable stages 3 and 4 (14%). Our results
      identify two regions of frequent allelic loss: the first at the locus D9S1849 and
      the second at the locus D9S157. These regions appear to be distant from CDKN2A
      and CDKN2B loci suggesting that other genes may be involved in 9p deletion.
      Finally, our data show that 9p deletion is more frequent in tumors of patients
      with a favorable prognosis, indicating that deleted genes may not be crucial for
      tumor progression.

PMID- 12072203
TI  - Newly established clear cell sarcoma (malignant melanoma of soft parts) cell line
      expressing melanoma-associated Melan-A antigen and overexpressing C-MYC oncogene.
AB  - Clear cell sarcoma (CCS), malignant melanoma of soft parts, is a rare malignant
      tumor with a poor prognosis. In this study, a CCS cell line, designated MP-CCS
      SY, was established from a metastatic tumor of a 17-year-old Japanese girl that
      originated in the left Achilles tendon. A small number of melanosomes were
      detected in the cytoplasm by electron microscopy. The melanosomes immunoreacted
      with two melanoma-associated antibodies, HMB45 and Melan-A. A Western blot
      demonstrated the existence of a Melan-A antigen in this cell line. Although a
      t(12;22)(q13;q12), which is characteristic of CCS, was not identified by a
      chromosomal analysis with conventional banding techniques, fluorescence in situ
      hybridization analysis with painting probes of chromosomes 12 and 22 revealed the
      insertion of a chromosome 12 fragment into one of the long arms of chromosome 22.
      The chimeric EWS/ATF1 transcript was detected by the reverse transcriptase
      polymerase chain reaction. Extra copies and structural abnormalities of
      chromosome 8 were observed. Overexpression of c-myc mRNA was detected by Northern
      blot analysis and may have a role in malignant progression of CCS. The
      availability of this MP-CCS-SY cell line will help to understand the molecular
      biology of this malignancy and should be useful as a tool for developing an
      immunotherapy.

PMID- 12072204
TI  - Infantile and adult testicular germ cell tumors. a different pathogenesis?
AB  - Most adult testicular germ cell tumors have a characteristic chromosomal
      abnormality that is an isochromosome 12p [i(12p)]. Furthermore, these tumors are
      characterized by a chromosome number in the triploid range and gains and losses
      of (parts of) specific chromosomes. Cytogenetic investigation of three cases of
      infantile testicular germ cell tumors, all diagnosed as yolk sac tumors, revealed
      highly abnormal karyotypes. We found one case to be diploid; the other two cases
      were in the hypertriploid/hypotetraploid range. Structural abnormalities of
      chromosomes 1, 3, and 6 were recurrent and no i(12p) was found. Our results,
      together with data from the literature, suggest that infantile and adult
      testicular germ cell tumors have a different origin and pathogenetic pathway.
      Aberrations of chromosomes 1, 3, and 6 may play an important role in the
      pathogenesis of infantile testicular yolk sac tumors.

PMID- 12072205
TI  - Compilation of published comparative genomic hybridization studies.
AB  - The power of comparative genomic hybridization (CGH) has been clearly proven
      since the first paper appeared in 1992 as a tool to characterize chromosomal
      imbalances in neoplasias. This review summarizes the chromosomal imbalances
      detected by CGH in solid tumors and in hemopathies. In May of 2001, we took a
      census of 430 articles providing information on 11,984 cases of human solid
      tumors or hematologic malignancies. Comparative generic hybridization has
      detected a number of recurrent regions of amplification or deletion that allows
      for identification of new chromosomal loci (oncogenes, tumor suppressor genes, or
      other genes) involved in the development, progression, and clonal evolution of
      tumors. When CGH data from different studies are combined, a pattern of nonrandom
      genetic aberrations appears. As expected, some of these gains and losses are
      common to different types of pathologies, while others are more tumor-specific.

PMID- 12072206
TI  - Establishment and characterization of human metastatic hepatocellular carcinoma
      cell line.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      with a poor prognosis. Recently, we established a HCC cell line from a metastatic
      HCC tumor. GTG banding analysis was performed and the karyotype showed that this
      metastatic HCC cell line is a hypertriploid (71-78 chromosomes) with a large
      marker chromosome containing a long homogeneously staining region (hsr).
      Comparative genomic hybridization was applied to characterize the chromosomal
      alterations in this metastatic HCC cell line. The results showed that the hsr was
      composed of amplified DNA sequences from 11q13. Further characterization of the
      hsr may lead to the isolation of the putative amplified oncogene at 11q13.

PMID- 12072207
TI  - A new translocation that rearranges the AML1 gene in a patient with T-cell acute
      lymphoblastic leukemia.
AB  - The AML1 gene (also known as RUNX1 or CBFA2), located in chromosome band 21q22,
      encodes a transcription factor which heterodimerizes with the CBFbeta protein
      forming a complex called human core binding factor (CBF). The CBF complex appears
      to regulate a number of genes important for hematopoiesis. AML1 is one of the
      most common targets of chromosomal rearrangements in human leukemias and has been
      involved in 14 chromosomal translocations to date. Here we report a new
      chromosomal translocation, t(4;21)(q31;q22) that disrupts the AML1 gene in a 12
      year-old boy with newly diagnosed T-cell acute lymphoblastic leukemia (ALL). This
      is the first reported chromosomal translocation where AML1 is rearranged in
      childhood T-cell ALL. By metaphase fluorescence in situ hybridization analysis,
      the AML1 breakpoint was mapped using recombinant phage clones, and shown to be
      either immediately upstream or downstream of exon 5.

PMID- 12072208
TI  - Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid
      leukemia following chemotherapy with DNA-topoisomerase II inhibitors for
      Langerhans cell histiocytosis.
AB  - We report a new case of therapy-related acute myeloid leukemia in a child with
      Langerhans cell histiocytosis. This patient was previously treated with a
      protocol of multidrug chemotherapy, containing a relatively low dose of etoposide
      (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the
      patient returned to the hospital with fever and anemia. The white blood cell
      count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration
      with French-American-British acute myeloid leukemia classification M4 blast
      cells. The patient did not respond to an intensive treatment with high dose ARA-C
      and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast
      cells was a t(11;11)(p13 -15;q23), that has not been described before in a
      secondary leukemia case.

PMID- 12072209
TI  - Experimental inoculation of domestic cats (Felis domesticus) with Sarcocystis
      neurona or S. neurona-like merozoites.
AB  - Sarcocystis neurona is the parasite most commonly associated with equine
      protozoal myeloencephalitis (EPM). Recently, cats (Felis domesticus) have been
      demonstrated to be an experimental intermediate host in the life cycle of S.
      neurona. This study was performed to determine if cats experimentally inoculated
      with culture-derived S. neurona merozoites develop tissue sarcocysts infectious
      to opossums (Didelphis virginiana), the definitive host of S. neurona. Four cats
      were inoculated with S. neurona or S. neurona-like merozoites and all developed
      antibodies reacting to S. neurona merozoite antigens, but tissue sarcocysts were
      detected in only two cats. Muscle tissues from the experimentally inoculated cats
      with and without detectable sarcocysts were fed to laboratory-reared opossums.
      Sporocysts were detected in gastrointestinal (GI) scrapings of one opossum fed
      experimentally infected feline tissues. The study results suggest that cats can
      develop tissue cysts following inoculation with culture-derived Sarcocystis sp.
      merozoites in which the particular isolate was originally derived from a
      naturally infected cat with tissue sarcocysts. This is in contrast to cats which
      did not develop tissue cysts when inoculated with S. neurona merozoites
      originally derived from a horse with EPM. These results indicate present
      biological differences between the culture-derived merozoites of two Sarcocystis
      isolates, Sn-UCD 1 and Sn-Mucat 2.

PMID- 12072210
TI  - Pattern of recognition of Neospora caninum tachyzoite antigens by naturally
      infected pregnant cattle and aborted foetuses.
AB  - Different aspects of Neospora tachyzoite antigen recognition by Neospora-infected
      heifers and cows and aborted foetuses were studied. The pattern of antigen
      recognition and the relationship between IFAT titres and number of Neospora
      antigens detected, were evaluated. In addition, the tachyzoite antigens involved
      in the humoral immune response developed against infection in normal cows and
      cows that aborted were also characterised throughout pregnancy. Comparison of
      tachyzoite antigen recognition was carried out in 13 thoracic and/or abdominal
      fluids from Neospora aborted foetuses and 33 sera from Neospora infected cows
      that had aborted. The kinetics of Neospora-antigen recognition was studied in
      Neospora-infected heifers and cows that had aborted foetuses (7) or not (14)
      during pregnancy. Based on the frequency and intensity of recognition, four IDAs
      17-18, 34-35, 37 and 60-62kDa antigens-have been described. Moreover, a
      correlation was found between Western blot results and IFAT titres in both age
      groups. In relation to antigen recognition throughout pregnancy by seropositive
      cows that had aborted or not, the antibody fluctuations throughout pregnancy
      described in the literature could be due to differences in the intensity and
      frequency of recognition of particular antigens, especially the 17-18kDa antigen.
      We emphasize the important role that the 17-18kDa antigen could play in the
      serological diagnosis of Neospora infection in cattle as this was intensely
      detected in 100% of the animals.

PMID- 12072211
TI  - Haemaphysalis qinghaiensis ticks transmit at least two different Theileria
      species: one is infective to yaks, one is infective to sheep.
AB  - Adult Haemaphysalis qinghaiensis ticks from Gannan area, where ovine theileriosis
      is prevalent but bovine theileriosis has not been reported, transmitted Theileria
      parasites to yaks and sheep. Blood from the infected yak contained Theileria
      parasites that were infective to yaks, but not sheep. In contrast, blood from the
      infected sheep did not contain Theileria parasites infective to yaks. These
      results suggested that the ticks from the Gannan area were infected with two
      species of Theileria one which specifically parasitises yaks, one which
      parasitises sheep. Both infections were more aggressive in splenectomised hosts
      as compared to intact host. Adult H. qinghaiensis ticks from Zhanjiachuan area,
      where ovine theileriosis is prevalent but where no yaks are raised, transmitted
      Theileria parasites to ovine, but not yaks. Taken together these results indicate
      that H. qinghaiensis ticks may be infected with two different Theileria species.
      The species infective for sheep could be related to the newly recognised, but not
      yet named, pathogen recently reported in small ruminants in China. The species
      infective for yaks appears to be benign and is morphologically similar to
      parasites of the Theileria sergenti/orientalis/buffeli group.

PMID- 12072212
TI  - Cryptosporidium andersoni from a Danish cattle herd: identification and
      preliminary characterisation.
AB  - In November 1997, Cryptosporidium andersoni, for the first time, was isolated
      from a Danish heifer. The isolate was characterised morphologically, molecularly,
      and furthermore inoculated into mice and one calf. Data on the distribution of
      cryptosporidia in the herd of origin were obtained at two separate visits in
      December 1997 and April 1998. C. andersoni was detected in 27 (19.0%) of 142
      cattle examined at the first visit, whereas C. parvum was found in six (4.2%). At
      the following visit 42 (28.0%) of 150 cattle excreted C. andersoni, while 25
      (16.7%) were positive for C. parvum. Oocysts of the Danish C. andersoni isolate
      were ovoid, 7.3(6.5-8.0) x 5.7(5.0-7.0) microm(2) (n=25), with smooth,
      colourless, single layer oocyst wall and distinct oocyst residuum. The length to
      width ratio was 1.27 (1.14-1.40, n=25). The identification was verified by
      sequencing of a 246bp fragment of the rDNA, which was identical to
      Cryptosporidium muris, the calf genotype (AF093496). The Danish C. andersoni
      isolate was not transmissible to mice, whereas oocysts were detected in the
      faeces of one experimentally infected calf from 25 days post-infection (DPI) and
      shed intermittently at low numbers until 165 DPI, the day of euthanasia. No
      macroscopic or microscopic changes that could be attributed to infection with C.
      andersoni were seen in the gastro-intestinal tract of the experimentally infected
      calf following necropsy and histological examination. This is to our knowledge
      the first report of C. andersoni in Scandinavia.

PMID- 12072213
TI  - Theileria parva epidemics: a case study in eastern Zambia.
AB  - This paper presents the results of the follow-up of three sentinel herds between
      1994 and 2000 during an East Coast fever (ECF) epidemic in eastern Zambia. The
      animals of the sentinel herds were closely monitored clinically and serologically
      together with detailed Rhipicephalus appendiculatus counts. Peaks of disease
      incidence occurred in the rainy season (December-February) and the dry months of
      May-July with nymph-to-adult tick transmission dominating the infection dynamics.
      A second wave of adult R. appendiculatus at the start of the dry season is
      essential for the occurrence of a full-blown epidemic while the size of the
      susceptible cattle population acts as a most important limiting factor. The
      majority of adult cattle of the sentinel herds became infected less than 2 years
      after the introduction of the disease. The median age at first contact for calves
      born towards the end of the study (1999) was about 6 months. The case-fatality
      ratio (including sub-clinical cases) is estimated at 60%. It is argued that part
      of the so-called 'natural mortality' is actually due to ECF and that ECF
      occurrence and mortality are systematically underestimated. The direct financial
      cost of the epidemic, based on loss of animals and cost of treatment only and
      calculated over 4 years running, is estimated at about 6 US dollars per year per
      animal at risk. The value of the traditional seroprevalence survey as a tool for
      monitoring ECF epidemiology is put in question and the prevalence of maternal
      antibodies in new-born calves, reflecting the immune status of the dam
      population, is introduced as an alternative. It is demonstrated that an efficient
      immunisation campaign should concentrate its efforts in the period of low adult
      R. appendiculatus abundance (July-October).

PMID- 12072214
TI  - Performance characteristics of an enzyme-linked immunosorbent assay for the
      detection of liver fluke (Fasciola hepatica) infection in sheep and cattle.
AB  - AIM: To validate an enzyme-linked immunosorbent assay (ELISA) for the detection
      of antibodies against liver fluke (Fasciola hepatica) in sheep and cattle sera.
      METHODS: Gold-standard sera from sheep and cattle of known infection status, i.e.
      sera from non-infected animals and from animals known to be infected with F.
      hepatica were assayed with a commercially available ELISA and results analysed by
      ROC analysis. RESULTS: The ROC analysis suggested cut-offs that were considerably
      lower than those suggested by the manufacturer, yet the ELISA performed with high
      sensitivity and specificity, 98 to 100%, respectively for sheep and cattle sera.
      For bovine sera, particularly good discrimination between positive and negative
      sera was observed. Infection in experimentally infested animals could be
      demonstrated 7-8 weeks earlier than with classical parasitological techniques.
      CONCLUSIONS: The analysis of the ELISA's performance demonstrated high
      sensitivity and specificity. ROC analyses optimised the cut-off point suggested
      by the manufacturer of the commercial diagnostic assay. Diagnosis of infection
      with F. hepatica was achieved much earlier than is possible with current
      parasitological techniques. This could help with the control of fasciolosis,
      enabling treatment before clinical manifestation of the disease.

PMID- 12072215
TI  - A preliminary analysis of proteolytic activity of excretory-secretory products
      from Cyathostominea.
AB  - The excretory-secretory product (ESP) derived from Cyathostominea in vitro was
      assessed, in terms of subunit composition, and proteolytic activity using as
      substrates azocasein and two synthetic fluorogenic peptides. Sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) resolved 13 subunits, and
      the presence of the protein cysteine proteinase activator dithiothreitol (DTT)
      revealed 21 subunits. DTT also enhanced azocaseinolysis, and hydrolysis of
      carbobenzoxy-phenylalanyl-arginine-7-amido-4-methylcoumarin (Z-Phe-Arg-NHMec) and
      carbobenzoxy-arginyl-arginine-7-amido-4-methylcoumarin (Z-Arg-Arg-NHMec). At the
      optimum pH of 5.5, hydrolysis of Z-Phe-Arg-NHMec was three-fold greater than that
      of Z-Arg-Arg-NHMec suggesting that the proteolytic specificities of the ESP are
      more like those of papain or cathepsin L, rather than cathepsin B. In SDS-PAGE
      gelatin gels, DTT was a requirement for proteolysis by the ESP. Optimum
      resolution was at pH=5.5, resolving six bands ranging from 114-20kDa. Cysteine
      proteinase inhibitors abolished all gelatinolytic activity at the pH values
      tested. Such data indicate the presence of cysteine-class proteinases in the ESP
      of Cyathostominea.

PMID- 12072216
TI  - The effects of ivermectin and moxidectin on egg viability and larval development
      of ivermectin-resistant Haemonchus contortus.
AB  - The in vivo effects of ivermectin and moxidectin on egg viability and larval
      development of ivermectin-resistant Haemonchus contortus were examined over time
      after anthelmintic treatment of sheep. Twenty merino sheep, (12 months old) were
      allocated to five treatment groups and infected with ivermectin-resistant H.
      contortus. Thirty one days later, the sheep were treated with intraruminal
      ivermectin capsules, oral ivermectin, oral moxidectin or injectable moxidectin at
      the manufacturer's recommended dosages, or left untreated. At various times up to
      112 days after treatment, faecal egg counts (FEC) were determined and development
      rates of infective larvae (L3) cultured in faeces or on agar were measured. Eggs
      in faecal cultures from ivermectin capsule treated sheep showed reduced L3
      development percentages in comparison to faecal cultures from untreated sheep.
      Eggs from ivermectin capsule treated sheep, isolated from faeces, and cultured on
      agar showed similar L3 development to eggs from control sheep. These results
      demonstrate an inhibitory effect of excreted ivermectin in faeces on larval
      development of ivermectin-resistant H. contortus. L3 development in faecal
      culture from animals receiving oral ivermectin were reduced for only 3 days after
      treatment. Faecal egg counts and development of L3 larvae in both culture systems
      from moxidectin treated sheep were low, due to the high efficacy of the drug. Egg
      counts in moxidectin treated sheep were reduced by approximately 90% 24h after
      treatment, before decreasing to almost 100% at 48h, suggesting that the current
      quarantine recommendation of holding sheep off pasture for 24h after treatment
      may still lead to some subsequent pasture contamination with worm eggs.

PMID- 12072217
TI  - Efficacy of moxidectin 1% injectable and 0.2% oral drench against natural
      infection by Dictyocaulus filaria in sheep.
AB  - Two separate trials (I and II) with 34 and 32 Churra ewes, respectively, and
      distributed into two groups, have been carried out to evaluate the efficacy of
      two different formulations of moxidectin at a dose rate of 0.2mg/kg body weight
      (b.w.) against natural infection by Dictyocaulus filaria in sheep. Trial I was
      designed to evaluate a 1% moxidectin injectable formulation, whereas in trial II
      a 0.2% moxidectin oral drench formulation was used. The efficacy was measured on
      the basis of the reduction of the faecal larval counts and of adult worm
      recoveries at slaughter. In each trial, a group of animals was treated on day 0
      with moxidectin 1% injectable or moxidectin 0.2% oral drench and the other group
      acted as untreated control. When the faecal larval counts was compared within the
      treated groups, the efficacy was over 95% until day +13, and 100% at the
      remainder of the sampling dates after the application of injectable moxidectin,
      whereas in trial II, the larvae per gram (lpg) of faeces increased until the
      first sampling time post treatment (p.t.), day +6, and zero counts were recorded
      for all animals by the following days. On the basis of adult worm recoveries at
      necropsy, the efficacy of the treatment was 100% in both trials, however, adult
      worms were detected at slaughter for all control sheep. These results indicate
      that moxidectin 1% injectable and moxidectin 0.2% oral drench, administered at
      0.2mg/kg b.w., were 100% effective against D. filaria infection in sheep. No
      adverse reactions to the treatments were observed in the animals.

PMID- 12072218
TI  - Impact of management interventions on helminth levels, and body and blood
      measurements in working donkeys in South Africa.
AB  - The aim of the study was to determine the effect of alternative management
      interventions on levels of nematodes and the condition of working donkeys in
      South Africa. Twenty-four adult donkeys (Equus asinus) within an area of 200km
      radius were randomly allocated to eight paddocks. Two replicates each of three
      management interventions together with a control group were tested in a 16-month
      study. The interventions included monthly removal of feces from paddocks where
      the donkeys grazed, a pre-winter moxidectin treatment, and a combination of a pre
      winter moxidectin treatment and monthly fecal removal. The influence of the
      different interventions on the nematode fecal egg counts, animal live weights,
      body condition scores and general blood chemistry were compared. In addition,
      herbage samples were collected from the pastures in each paddock to determine the
      number of third-stage larvae (L(3)) per kg dry matter. At the end of the study
      worm recoveries and counts were performed on eight of the animals following
      euthanasia. The cyathostomes represented the largest portion of the helminth
      species composition in both the fecal egg counts and larval cultures. Monthly
      fecal removal alone did not significantly reduce the L(3) on pasture and
      consideration of more frequent removal is discussed. Pre-winter moxidectin
      treatment resulted in a 100% reduction in fecal egg counts, an average egg
      reappearance period of 42-55 days, a reduced average egg count for up to 8
      months, and reduced total helminth burdens in all the treated donkeys. It also
      resulted in improved live weights, hemoglobin concentration, packed cell volumes
      and to some extent body condition score of the donkeys.

PMID- 12072219
TI  - Effect of tetracycline on development of Anaplasma marginale in cultured Ixodes
      scapularis cells.
AB  - Infections of the tick-borne ehrlichial pathogen, Anaplasma marginale, in cattle
      have been controlled, in part, by administration of low doses of tetracycline.
      Recently, a cell culture system was developed for A. marginale using a tick cell
      line derived from embryonic Ixodes scapularis. This study was designed to
      determine the effect of tetracycline on A. marginale propagated in a tick cell
      culture assay. Various concentrations of tetracycline (0, 0.01, 0.10, 1.0, 5, 10,
      20 or 100 microg/ml) were added in medium to cultures 48h after cell monolayers
      were inoculated with A. marginale. A. marginale growth in the drug treated and
      control cultures was subsequently evaluated by indirect ELISA at 7 days post
      infection (PI) and daily by light and electron microscopy (LM and EM).
      Infectivity of the culture-derived A. marginale was determined by inoculation of
      susceptible cattle with treated and untreated control cultures. Tetracycline
      doses of 5, 10, 20 and 100 microg/ml resulted in significant inhibition of A.
      marginale growth as determined by ELISA. Morphologic deterioration of Anaplasma,
      as determined by LM and EM, occurred in cultures treated with the same drug
      concentrations. A. marginale replication, inhibited in cultures treated on days 2
      6 PI with 20 microg/ml tetracycline, was not apparent 96 days after antibiotic
      removal. Infected cell cultures treated with medium containing 20 microg/ml
      tetracycline proved to be non-infective when inoculated into susceptible
      splenectomized calves. All parameters studied herein demonstrated that
      tetracycline killed A. marginale in cultured tick cells. The Anaplasma-tick cell
      culture drug assay therefore, would be useful for screening and evaluating novel
      antibiotics for control of anaplasmosis.

PMID- 12072220
TI  - Evaluation of the efficacy of fipronil formulations in the treatment and control
      of biting lice, Trichodectes canis (De Geer, 1778) on dogs.
AB  - The efficacy of FRONTLINE SPRAY (0.25% (w/v) fipronil), FRONTLINE SPOT-ON FOR
      DOGS (10% (w/v) fipronil) and FRONTLINE PLUS FOR DOGS (10% (w/v) fipronil and 9%
      (S)-methoprene) against the biting louse Trichodectes canis on dogs was confirmed
      under laboratory conditions. A field study evaluated the efficacy of a single
      topical application of FRONTLINE SPRAY and FRONTLINE SPOT-ON against the parasite
      on dogs. A total of 48 dogs of mixed breeds, both sexes, aged 2 months-7 years
      and weighing 1.8-37.0kg were used. The animals were either experimentally
      (laboratory study) or naturally (field study) infested with lice. Dogs were
      housed individually in order to prevent contact between animals. In the
      laboratory study, animals were allocated based on pre-treatment louse counts from
      38 hair coat-partings per animal. Dogs were randomly assigned to the four
      treatment groups: (1) untreated control; (2) FRONTLINE SPRAY, at 6ml/kg; (3)
      FRONTLINE SPOT-ON as per label and (4) FRONTLINE PLUS as per label. Dogs in
      treatment groups 2-4 were treated twice topically on Days 0 and 28. The number of
      live lice in the 38 hair coat-partings per animal were counted on Days 2, 7 and
      weekly to Day 63. In addition, a whole body comb count was performed on Day 63.
      No live T. canis were found on dogs treated with FRONTLINE formulations at any
      post-treatment examination. The difference from controls was significant (P<0.01)
      for each product at each examination. Based on the whole body comb count at Day
      63, the efficacy of each product was determined to be 100%. In the field study,
      dogs were allocated in strict order of presentation. Dogs were randomly allocated
      to one of the three treatment groups: (1) BOLFO collar (propoxur); (2) FRONTLINE
      SPRAY, at 6ml/kg and (3) FRONTLINE SPOT-ON as per label. Dogs were treated once
      topically on Day 0. The number of live lice was determined by whole body searches
      on Days 0 (pre-treatment), 2, 28 and 42. Louse counts of dogs treated with either
      FRONTLINE SPRAY, or FRONTLINE SPOT-ON were not different than those of dogs
      receiving the propoxur collar. The efficacy was determined to be >98% on Day 2
      and, 100% on Days 28 and 42 in all treatment groups. The results of these studies
      demonstrate that fipronil in topical formulations is effective for treatment and
      control of biting lice (T. canis) infestations on dogs.

PMID- 12072221
TI  - Parasites from farmed ostriches (Struthio camelus) and rheas (Rhea americana) in
      Europe.
AB  - During a 4-year-period, more than 500 ostriches and several rheas, all born in
      European countries and raised in Spain and Portugal, have been analyzed for the
      presence of ectoparasites and endoparasites. A total of 29 parasite species have
      been found, most of them of the gastrointestinal tract. Some of the helminth
      species found may represent spureous parasitosis, as only the eggs (of an ascarid
      and a trematode) were found in some samples. From the organisms identified, the
      ectoparasites (lice-Struthiolipeurus rheae, S. nandu; mites-Dermoglyphus
      pachycnemis, Gabucinia bicaudata), helminths (cestoda-Houttuynia struthionis- and
      nematoda-Libyostrongylus sp., Codiostomum struthionis-) and the ciliate
      Balantidium struthionis are known as ratite specific parasites. Capillaria eggs
      and larvae were also found; there are no previous records of this parasite from
      ostriches, and the data available do not allow to do a temptative specific
      diagnosis. Among protozoa, most of the species now found are described for the
      first time in ratites. They include organisms also found in other birds
      (Trichomonas gallinae, Tetratrichomonas gallinarum, Chilomastix gallinarum,
      Spironucleus meleagridis and Pleuromonas jaculans), and organisms whose specific
      status cannot be established until further analysis are performed
      (Cryptosporidium sp., Eimeria sp. and/or Isospora sp., Entamoeba sp. of the one
      nucleate and of the eight-nucleate mature cyst groups, Endolimax sp., Iodamoeba
      sp., Monocercomonas sp., Retortamonas sp., Giardia sp., Blastocystis sp. and
      euglenids).

PMID- 12072222
TI  - Haematological profiles in pure bred cattle naturally infected with Theileria
      annulata in Saudi Arabia.
AB  - The Abbott Cell Dyn 3500 haematology analyzer was employed to study
      haematological parameters in 41 adult and young Friesian cattle naturally
      infected with Theileria annulata in the Qassim region of Saudi Arabia. Comparison
      was made with clinically healthy adult and young Friesian cattle. Changes in
      blood parameters in T. annulata-infected cattle indicated severe macrocytic
      hypochromic anaemia, panleukopenia, lymphocytopenia, eosinopenia, neutropenia and
      thrombocytopenia but no reticulocytosis.

PMID- 12072223
TI  - Antigenic characterization of morphologically distinct Anaplasma marginale
      isolates using a panel of monoclonal antibodies.
AB  - The present study, describes the antigenic characterization of a Brazilian
      isolate of Anaplasma marginale with appendage (tail). A panel of monoclonal
      antibodies (McAbs) was produced and tested by the indirect fluorescent antibody
      test (IFAT), ELISA and Western blotting, and used to characterize two isolates of
      A. marginale (one with appendage and another without appendage). Among the clones
      produced, eight recognized antigenic proteins, with molecular weights varying
      from 18.4 to 66kDa. In Western blotting, the McAb reacted against a 45kDa
      antigen, which was shown, by the IFAT, to be located in the tail.
      Immunocytochemistry confirmed the tail specificity of the monoclonal reacting
      against the 45kDa antigen. The panel of McAb produced has a potential use in
      discriminating morphologically distinct A. marginale isolates. The present study,
      demonstrates the occurrence of antigenic diversity among Brazilian isolates of A.
      marginale.

PMID- 12072225
TI  - Inflammatory cytokines and antigen presenting cell activation.
AB  - Immune responses are stimulated in response to threats against health. In
      animals, defense against infectious agents, particularly rapidly growing viruses
      and bacteria, requires an immediate response to limit growth and dissemination,
      and then stimulation of a more prolonged, specific immunity to prevent re
      infection. The process by which animals meet the dual needs of an immediate
      response to danger and initiation of long-term protection is substantially
      influenced by inflammatory cytokines produced primarily by macrophages and
      professional antigen presenting cells (APCs). Inflammatory cytokines mobilize the
      immune system in response to danger and increase the efficiency of an immune
      response as effectors of APC function. Here we review the evidence for the
      involvement of inflammatory cytokines in immune induction and as mediators of APC
      activity, with a particular emphasis on swine and on the induction of immunity at
      mucosal surfaces. The vast majority of infections occur at mucosal surfaces of
      the enteric, respiratory and reproductive tracts, and induction of protective
      immunity at these sites is particularly challenging. Induction of immunity at
      mucosal surfaces of the small intestine is greatly facilitated by the oral
      adjuvant, cholera toxin (CT). CT potentiates inflammatory cytokine and
      costimulatory molecule expression in macrophages, and stimulates humoral and cell
      mediated immune responses both locally and systemically. These observations are
      consistent with the hypothesis that activation of APCs is a key step in the
      induction of antigen-specific immunity, and that inflammatory cytokine expression
      is a hallmark of activated APC function. The efficacy of vaccine adjuvants,
      particularly in the context of mucosal immunity, may be determined by their
      ability to induce a controlled inflammatory response in gut-associated lymphoid
      tissue, characterized by the expression of various costimulatory molecules and
      inflammatory cytokines. Thus, elucidation of the patterns of inflammatory
      cytokine expression and features of APC activation will help to facilitate the
      rational development of more efficacious vaccines.

PMID- 12072226
TI  - Co-stimulation and modulation of the ensuing immune response.
AB  - As a consequence of the central role of dendritic cells (DC) in stimulating
      primary immune responses any bias in the response introduced by the DC has the
      potential for having a long-term effect on immunity. Examination and analysis of
      ruminant afferent lymph dendritic cells derived by cannulation allows studies on
      the properties of ex vivo DC that is not possible in humans and rodents and
      information can be derived from ruminants that has implications of generic
      relevance. Previous studies have identified two major populations of DC in
      afferent lymph draining the skin of cattle that differ in their capacity to
      stimulate CD4 and CD8 T cells. Differences in expression of cytokine transcripts
      have now been shown for the two types of DC. The CD11a(+)/SIRPalpha(-) population
      synthesised more IL-12, whilst the CD11a(-)/SIRPalpha(+) population produced more
      IL-10. This is likely to affect the bias of the immune response following
      presentation of antigen to T cells by one DC sub-population or the other. An
      inability to synthesise IL-1alpha was the reason for the failure of the
      CD11a(+)/SIRPalpha(-) DC to stimulate CD8 T cells. This property would
      potentially affect the induction of CD8 responses. Expression of the co
      stimulatory molecules CD80, CD86 and CD40 appeared similar for both DC
      populations and not to relate to differences in function. A further examination
      of the SIRPalpha molecule on DC indicated that on cross-linking it was tyrosine
      phosphorylated and that it recruited the SHP-2 protein phosphatase. Associated
      with this was a blocking of TNFalpha secretion on exposure to LPS. The
      interaction of SIRPalpha with its ligand CD47 on T cells appeared to be an early
      event in the stimulation of T cells as binding of the ligand was reduced on
      activated T cells. CD26 was identified as another molecule expressed by the
      SIRPalpha(-) DC sub-population. This is reported to have an enzymatic activity on
      certain chemokines that could result in the promotion of a Th1 bias.A model is
      proposed that takes these observations into account in which SIRPalpha(-) DC
      would be expected to promote a Th1 biased response and the SIRPalpha(+) DC a more
      balanced one.

PMID- 12072227
TI  - Mucosal memory--maintenance and recruitment.
AB  - The maintenance of IgA antibody responses at mucosal surfaces is the outcome of
      influences on IgA precursor cell dissemination from the mucosal inductive sites,
      such as the intestinal Peyer's patches, their selective extravasation at mucosal
      effector sites and the retention and local proliferation of these cell
      populations under local influences. Examination of these local post
      extravasational effects has implicated cytokines as major regulatory elements in
      this process. This paper will address the role of cytokines in induction and
      expression of IgA responses and the differential requirements for cytokine
      signals among IgA-committed B cell subsets in both rodent and domestic livestock
      species. The way in which cytokines influence local immunity in the gut with
      respect to microbial and parasitic challenge and comparative cytokine effects in
      extra-intestinal sites, particularly the eye, will be presented, and
      opportunities for therapeutic interventions to modify cytokine expression will be
      discussed.

PMID- 12072228
TI  - T-helper cells from naive to committed.
AB  - T-helper cells play a central role in the onset and regulation of the antigen
      specific immune response. In swine, two subpopulations of CD4 positive T-helper
      cells could be defined in extra-thymic compartments. Both differ in the surface
      antigen expression of distinct antigens. Besides the CD4(+)CD8(-) T-helper cell
      subpopulation representing the phenotype of T-helper cells known from other
      species, in swine CD4(+) T-helper cells exist showing expression of CD8alpha and
      MHCII molecules.In primary in vitro immune reactions after simulation with SEB
      the main response is distributed to the CD4(+)CD8(-) T-cell subpopulation, which
      contains the majority of naive T-helper cells. During the immune response
      CD8alpha as well as MHCII molecules are expressed on the surface of activated T
      helper cells. This in vitro maturation is combined with a down-regulation of
      CD45RC. Thus, activated T-helper cells represent a cell phenotype with high
      similarity to the second porcine T-helper cell subpopulation. This
      CD4(+)CD8alpha(+) subpopulation contains in its majority MHCII(+) and CD45RC(-)
      cells. In a secondary in vitro immune response against classical swine fever
      virus only the CD4(+)CD8(+) T-helper subpopulation is able to respond. Therefore,
      T-helper memory cells can be distributed to this T-lymphocyte subpopulation. In
      summary, naive CD4(+)CD8(-)MHCII(-) porcine T-helper cells show an extra-thymic
      maturation to committed CD4(+)CD8alpha(+)MHCII(+) T-helper cells.

PMID- 12072229
TI  - Induction of mucosal immune responses and protection against enteric viruses:
      rotavirus infection of gnotobiotic pigs as a model.
AB  - Enteric viruses are a major cause of diarrhea in animals and humans. Among them,
      rotaviruses are one of the most important causes of diarrhea in young animals and
      human infants. A lack of understanding of mechanisms to induce intestinal
      immunity and the correlates of protective immunity in neonates has impaired
      development of safe and effective vaccines against enteric viruses. Studies of
      candidate vaccines using an adult mouse model of subclinical enteric viral
      infections often do not predict vaccine efficacy against disease evaluated in
      neonatal large animals. A series of studies have been conducted using a neonatal
      gnotobiotic pig model of rotavirus infection and diarrhea to identify correlates
      of protective immunity and to evaluate traditional and novel vaccine approaches
      for the induction of mucosal immune responses and protection to enteric viruses.
      Gnotobiotic pigs recovered from infection with virulent Wa human rotavirus (HRV)
      (mimic natural infection) had high numbers of intestinal IgA rotavirus-specific
      primary antibody-secreting cells (ASCs) and memory B-cells (to recall antigen)
      measured by ELISPOT assay, which correlated with complete protection against
      rotavirus challenge. Most short-term IgA memory B-cells were resident in the
      ileum, the major site of rotavirus replication. Spleen, not the bone marrow, was
      the major resident site for longer-term IgG memory B-cells. Candidate rotavirus
      vaccines evaluated in pigs for their ability to induce intestinal or systemic ASC
      and protection against rotavirus infection and diarrhea included attenuated live
      virus, inactivated virus, and baculovirus-expressed double-layered rotavirus-like
      particles (2/6-VLPs). In combination with those candidate vaccines, various
      adjuvants, delivery systems, and immunization routes were tested, including
      incomplete Freund's adjuvant for i.m. immunization, and a mutant Escherichia coli
      heat labile enterotoxin R192G (mLT) for i.n. immunization. It was shown that
      orally administered replicating vaccines were most effective for priming for
      intestinal IgA ASC and memory B-cell responses, but i.n. administered non
      replicating 2/6-VLPs plus mLT were effective as booster vaccines. We conclude
      that protective immunity depends on the magnitude, location, viral protein
      specificity, and isotype of the antibody responses induced by vaccination.
      Therefore highly effective enteric viral vaccines should: (i) induce sufficient
      levels of intestinal IgA antibodies; (ii) include viral antigens that induce
      neutralizing antibodies; and (iii) require the use of effective mucosal adjuvants
      or antigen delivery systems for non-replicating oral or i.n. vaccines.

PMID- 12072230
TI  - In vivo studies on cytokine involvement during acute viral respiratory disease of
      swine: troublesome but rewarding.
AB  - The early cytokines interferon-alpha (IFN-alpha), tumour necrosis factor-alpha
      (TNF-alpha), interleukin-1, -6 and -8 (IL-1, -6, -8) are produced during the most
      early stage of an infection. The activities of these cytokines have been studied
      extensively in vitro and in rodents, but in vivo studies on the role of these
      cytokines in infectious diseases of food animals are few. This review
      concentrates on in vivo studies of cytokine involvement in infectious respiratory
      diseases of swine, with an emphasis on viral infections. First evidence for the
      role of early cytokines in pneumonia in swine came from experimental infections
      with Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae. The role of
      TNF-alpha and IL-1 in the symptoms and pathology of porcine pleuropneumonia has
      recently been proven by use of an adenovirus vector expressing the anti
      inflammatory IL-10. In the authors' laboratory, studies were undertaken to
      investigate the relationship between viral respiratory disease and bioactive lung
      lavage levels of IFN-alpha, TNF-alpha, IL-1 and IL-6. Out of three respiratory
      viruses-porcine respiratory coronavirus (PRCV), porcine reproductive and
      respiratory syndrome virus (PRRSV) and swine influenza virus (SIV)-only SIV
      induced acute respiratory disease and severe lung damage by itself. Disease and
      lung pathology were tightly associated with the simultaneous production of IFN
      alpha, TNF-alpha, IL-1 and IL-6. In challenge studies of SIV-vaccinated pigs,
      levels of IFN-alpha, TNF-alpha and IL-6, but not IL-1 were correlated with
      clinical and virological protection. Multifactorial respiratory disease was
      reproduced by combined inoculations with PRCV or PRRSV followed by LPS from
      Escherichia coli. In comparison with the respective single inoculations, which
      were subclinical, there was a true potentiation of disease and production of TNF
      alpha, IL-1 and IL-6. TNF-alpha and IL-6 were best correlated with disease. In
      further studies, we will use more specific strategies to dissect the role of
      cytokines during viral infections.

PMID- 12072231
TI  - Antibodies as effectors.
AB  - Antibodies are critical in protection against extracellular microbial pathogens.
      Although antibodies also play a role in transplant/tumor rejection and in
      autoimmune disease, this paper focuses on defense against bovine infections.
      Effector mechanisms of different bovine isotypes, subisotypes and allotypes are
      discussed. The importance of antigen specificity is also stressed.

PMID- 12072232
TI  - New generation vaccines and delivery systems for control of bovine tuberculosis
      in cattle and wildlife.
AB  - Advances in the understanding of protective immune responses to tuberculosis are
      providing opportunities for the rational development of improved vaccines for
      bovine tuberculosis. Protection requires activation of macrophages through
      stimulation of a Th 1 type immune response. Ideally, a vaccine for cattle should
      induce protection without causing animals to react in a tuberculin test when
      exposed to Mycobacterium bovis. A number of new tuberculosis vaccines including
      attenuated M. bovis strains, killed mycobacteria, protein and DNA vaccines have
      been developed and many of these are being assessed in cattle. The requirements
      for a tuberculosis vaccine for wildlife differ from those for cattle. The major
      goal of a wildlife vaccine is to prevent the transmission of M. bovis to cattle
      and other wildlife. Although there are a number of technical problems associated
      with the development of a vaccine delivery system for wildlife, attenuated M.
      bovis vaccines administered via oral baits or aerosol spray to possums have
      already been shown to reduce the severity of a subsequent M. bovis infection.

PMID- 12072233
TI  - Identification of mechanisms of natural resistance to African trypanosomiasis in
      cattle.
AB  - Natural resistance to African trypanosomiasis in certain Bos taurus cattle in
      West Africa, called trypanotolerance, may hold solutions for control of this
      economically crippling disease. Comparison of immune responses between
      trypanotolerant and trypanosusceptible cattle have shown some differences in
      antibody response, complement level and cytokine expression, but it is not known
      whether these differences are the cause of resistance. Two experiments were
      carried out to assess the contribution of the immune and haemopoietic systems to
      trypanotolerance. The production of haemopoietic chimaeras from trypanotolerant
      and susceptible twin calves and comparison of their responses after infection
      with singleton calves, allowed an assessment of the role of the haemopoietic
      system in trypanotolerance. An in vivo depletion of CD4 cells in the two breeds
      allowed an appraisal of the role of T and B lymphocytes in trypanotolerance. The
      results of the two experiments suggest that natural resistance comprises at least
      two mechanisms, an innate mechanism that controls parasite growth, and another,
      involving the haemopoietic system, that is able to limit anaemia. This supports
      the hypothesis that innate mechanisms in trypanotolerant cattle are more
      efficient in controlling disease, making them less reliant on antibody responses.

PMID- 12072234
TI  - Antigen delivery systems and immunostimulation.
AB  - The immune system evolved to free the host from invading noxious pathogens.
      Vaccines are inoculated as a prophylactic measure in order to program the immune
      system for accelerated recognition and elimination of specific pathogens. During
      vaccination the immune system is exposed to attenuated or inactivated
      microorganisms, or their fragments. The immune response to these structures, in
      contrast to virulent pathogens, is often inadequate for the generation of memory
      cells or immune effector elements such as antibodies, perforines, granzymes or
      cytokines. Vaccine adjuvants help to overcome these limited responses. They
      provide instructive signals for the host immune system by mimicking the
      conditions associated with virulent infection. Hence, they either enhance and
      prolong expression of antigen components to reactive T cells in lymph nodes
      (signal 1) or they increase expression of membrane-bound or soluble costimulatory
      molecules (signal 2). The enhancement of both signals by vaccine adjuvants is not
      mutually exclusive. Moreover, adjuvants may encode a third signal instructing the
      type of immune reaction to be generated. Supported by animations this
      presentation addresses putative immunological concepts of vaccine adjuvant
      activity, a phenomenon long been known as "the immunologist's dirty little
      secret". Insight in the mechanisms that underlie adjuvant-induced
      immunostimulation and generation of memory cells will facilitate rational vaccine
      design.

PMID- 12072235
TI  - Immune modulation: the genetic approach.
AB  - As part of a comprehensive strategy to combat diseases, improving genetically
      resistance to diseases and therefore immune capacities of animals is more and
      more desirable. However, research is still needed to develop genetic tools that
      may be used. In this search, lines selected for various immune responses are used
      to study relevant immune markers. Chickens have been selected for six generations
      for three different in vivo immune responses: high antibody response, high cell
      mediated immune response and high phagocytic activity. Each line, selected for
      one trait, showed significant increase in immune capacity for this trait. In
      addition, results showed clearly independence between the three immune responses
      analyzed, meaning that a global approach is needed to improve immune capacity.
      Selected lines allow to follow genetic markers linked to immune response genes.
      In the different lines, different patterns in MHC gene frequency were observed
      and MHC alleles differed in their effects according to the immune trait. Some
      correlations were found between immune responses and production traits. The
      selected lines will be used to find other "known" immune response genes or
      "anonymous" genetic markers, which may become the future tools to modulate immune
      responsiveness of animals.

PMID- 12072236
TI  - Immunity in neonates.
AB  - Passively derived maternal immunity hampers active immunization of newborns.
      Further, an immature immune system contributes to a weak and Th2 polarized
      immunity. This state of immunity in early life sustains endemic infections in man
      and continuous reinfections in animal herds. The endemic infections of the young
      occur preferentially when the immune system is still functionally immature and
      when the low levels of maternal antibodies are no longer protective but yet
      blocks protective immune responses. Vaccines overcoming these problems would have
      strong positive effects on the herd health and environmental benefits. The Th2
      bias of the newborn is mediated by high levels of progesterone and Th2 cytokines
      produced in the maternal-fetal interface. The activity of the innate system is
      enhanced in the mother during the prepartus period, certainly having effects on
      the offspring. Newborn, 2-days-old, mice can be primed with Sendai virus envelope
      proteins as model antigens to induce Th1 or Th2 responses, dependent on the
      supplementation of the virus antigen formulation with Th1 or Th2 adjuvants. This
      priming has a strong life-long effect when complemented with subsequent boosts.
      However and importantly this priming effect can be modulated by adjuvants
      focusing for Th1 and Th2 when applied to the mice at 6 weeks of age, i.e. when
      they are immunologically adult. It has been shown in various species, besides
      mice, i.e. dog, sheep, horse and seal, that a strong Th1 driving adjuvant can
      induce immune response and protection in newborns when conventional vaccines
      fail. In conclusion, the Th2 bias prevailing around partus can be overcome by
      appropriate immunological treatments, permitting effective vaccination and
      protective immunity in the newborn.

PMID- 12072237
TI  - Modulating immune responses with dendritic cells: an attainable goal in
      veterinary medicine?
AB  - Dendritic cells (DCs) are antigen presenting cells that potently modulate immune
      responses with varying outcomes depending on the DC sub-population involved. To
      understand how DC sub-types arise, it is necessary to determine which factors
      influence their differentiation. At least three major sub-populations of DCs have
      been described in mice: CD4+/CD8- "myeloid" DCs, CD4-/CD8+ "lymphoid" DCs and
      Langerhans cell-derived DCs. Whilst somewhat comparable populations have been
      described in man, in most other species very little is known. The identification
      of cytokines which stimulate proliferation of DC precursors, and the observation
      that the cytokine environment influences the phenotype and the function of the
      DCs that subsequently develop, has provided a useful tool for evaluating these
      rare cells. We describe the influence of cytokines on the phenotype of DCs
      generated in the rat. Using bone marrow cells as the source of precursors we
      generated "myeloid-type" DCs from the adherent population using granulocyte
      macrophage colony stimulating factor (GM-CSF), IL-4 and Flt-3L or "lymphoid-type"
      DCs from the non-adherent population using cytokines which included IL-7, IL-3,
      SCF and TNFalpha. In order to facilitate similar approaches to the study of
      equine DCs we have identified the nucleotide sequence encoding GM-CSF from the m
      RNA of equine PBMC stimulated with Concanavalin A, amplified the cDNA by PCR and
      cloned it in eukaryotic and prokaryotic expression vectors. We report on the
      structure and function of this molecule.

PMID- 12072238
TI  - A sub-population of circulating porcine gammadelta T cells can act as
      professional antigen presenting cells.
AB  - A sub-population of circulating porcine gammadelta T cells express cell surface
      antigens associated with antigen presenting cells (APCs), and are able to take up
      soluble antigen very effectively. Functional antigen presentation by gammadelta T
      cells to memory helper T cells was studied by inbred pig lymphocytes immunised
      with ovalbumin (OVA). After removing all conventional APCs from the peripheral
      blood of immunised pigs, the remaining lymphocytes still proliferated when
      stimulated with OVA. When gammadelta T cells were further depleted, OVA specific
      proliferation was abolished, but reconstitution with gammadelta T cells restored
      proliferation. The proliferation was blocked by monoclonal antibodies (mAb)
      against MHC class II or CD4, and by pre-treatment of gammadelta T cells with
      chloroquine. These results indicate that a sub-population of circulating porcine
      gammadelta T cells act as APCs and present antigen via MHC class II.

PMID- 12072239
TI  - Role of bovine chemokines produced by dendritic cells in respiratory syncytial
      virus-induced T cell proliferation.
AB  - Respiratory syncytial virus (RSV) has been reported to induce the production of
      chemokines in the airway epithelia. Dendritic cells (DC) are the most potent
      antigen-presenting cells. They are located throughout the body and release
      chemokines in response to inflammation and infection. We have investigated the
      chemokine profile of bovine DC in response to exposure to bovine RSV (BRSV).
      Transcripts for several chemokines were detected by RT-PCR, subsequently cloned
      and expressed, and the products analysed by western blotting. To test the effect
      of the recombinant chemokines on RSV-induced T cell proliferation, DC were pulsed
      with BRSV, irradiated, and added to purified bovine CD4(+) T cells from RSV
      immune cattle in combination with various concentrations of recombinant
      chemokines, and the proliferative response of the T cells assessed. Eotaxin was
      the only chemokine, of those investigated, that specifically enhanced the T cell
      response to BRSV-pulsed DC. Addition of MIP-1alpha to control wells or to wells
      containing BRSV-pulsed DC had similar effects, suggesting non-specific
      stimulation of T cells. RANTES and MIP-3alpha did not seem to influence the
      proliferative response of T cells co-cultured with BRSV-pulsed DC. Thus, although
      BRSV induced the production of several chemokines by DC, only eotaxin promoted a
      BRSV specific CD4(+) T cell proliferative response.

PMID- 12072240
TI  - Analysis of the repertoire of cattle CD4(+) T cells reactive with bovine viral
      diarrhoea virus.
AB  - Cell-mediated immunity and CD4(+) cells in particular are important for the
      resolution of acute infection with non-cytopathic bovine viral diarrhoea virus
      (BVDV). CD4(+) T cells were shown to recognise virus-infected and non-infectious
      protein-pulsed APCs, whereas CD8(+) T cells recognised only virus-infected APCs.
      T cell recognition was strain cross-reactive and MHC-restricted. Using native and
      recombinant antigens, we identified the structural glycoprotein E2 and the non
      structural protein NS3 as dominant CD4(+) T cell determinants. The repertoire of
      CD4(+) T cell responses to E2 and NS3 was examined using inbred, homozygous
      cattle and overlapping synthetic peptides. The repertoire was biased toward
      conserved regions of NS3 and excluded the hypervariable regions of E2. The number
      of peptides that were recognised varied between animals but patterns could be
      distinguished in those animals that shared the same DRB3(*) allele. Of particular
      interest were: (i) a determinant that was recognised in the context of both
      DRB3(*) alleles (i.e. DRB3(*)2002 and DRB3(*)0701), (ii) two determinants that
      were juxtaposed to B cell sites, and (iii) a determinant that had structural
      analogy with a NS3 epitope previously described for the closely related hepatitis
      C virus. The minimum stimulatory sequence of the latter, NS3(397-414), was
      located to residues NS3(400-410).

PMID- 12072241
TI  - Mycobacterium paratuberculosis heat shock protein 70 as a tool in control of
      paratuberculosis.
AB  - Paratuberculosis in cattle is a chronic intestinal disease in which a distinctive
      cellular reactivity of a Th1-type preceeds the phase in which antibody titers are
      easily detectable and the animal becomes clinically ill. During infection with
      Mycobacterium avium ssp. paratuberculosis (M.a.p), a decrease in CD4 T-helper
      cells has been observed in the clinical phase. Our ultimate aim is to elicit a
      cytotoxic reaction against infected macrophages, using recombinant Hsp70 (rHsp70)
      of M.a.p. as a tool to shuttle antigen into the MHC class I antigen presentation
      pathway. To investigate the mechanism of rHsp70 as a carrier for antigen into the
      cell, we studied the interaction between APC and Fitc-labelled rHsp70, using FACS
      analysis and confocal microscopy. Interaction of rHsp70 with the cell surface of
      bovine APC, presumably via a receptor, was shown on monocytes, monocyte derived
      macrophages and dendritic cell (DC). The interaction is detectable on the
      complete population of freshly derived monocytes, although peak intensity of
      fluorescence is lower on these cells than on macrophages and DCs. DCs show
      interaction on a high percentage of the cells, with high intensity, while in the
      case of macrophages only a subpopulation interacts with rHsp70. Efficient uptake
      of rHsp70 as compared to OVA is shown. Preincubation of DC with unlabelled rHsp70
      leads to a decreased interaction with rHsp70-FITC. DC interacting with rHsp70 in
      addition showed high expression of MHC I, MHC II, Myd-1 (CD172a) and CD40.
      Further research will focus on loading of the rHsp70 with M.a.p. antigen for
      presentation in MHC class I.

PMID- 12072242
TI  - Molecular immunology--gene regulation and signal transduction.
AB  - Research on 'molecular immunology-gene regulation and signal transduction' in
      veterinary species is relatively new. The reason for its novelty is that until
      recently there have been very few tools with which we can work. Over the last 10
      years the veterinary immunology community has succeeded in generating panels of
      defined monoclonal antibodies (mAb) and cloned genes that has enabled such work
      to be started. More recently, quantitative, high-resolution analytical tools for
      veterinary species have begun to be developed; some of these are specific for
      veterinary species and others have been adapted from human or rodent systems. Of
      the species-specific tools that have recently been developed perhaps the most
      widely used are the immunoassays for cytokines, RNAase protection assays (RPAs)
      and in the near future oligonucleotide and EST-based microarrays. This
      presentation will describe some of these assays and discuss their relative
      advantages and disadvantages.

PMID- 12072244
TI  - Patterns of cytokine gene expression of naive and memory T lymphocytes in vivo.
AB  - Large-scale lymphocyte recirculation occurs only at the level of secondary
      lymphoid tissue. Cells enter lymph nodes via afferent lymph from the tissue and
      via arterioles from the blood. They exit only via the efferent duct. Afferent and
      efferent lymphocytes have distinct phenotypes; afferent lymphocytes have a
      'memory' phenotype, being CD62L(-)/CD45RA(-) and expressing high levels of CD2
      and CD11a; efferent cells are largely 'naive', being CD62L(+)/CD45RA(+) with low
      levels of CD2 and CD11a. We will show that functionally the efferent lymphocytes,
      like cells from the blood and spleen, can be activated in vitro only by dendritic
      cells. However, afferent lymphocytes are less stringent in their activation
      requirements and can be stimulated by both macrophages and dendritic cells. To
      explain these functional differences we have developed a multiprobe RNAase
      protection assay for 13 sheep cytokines (IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-8,
      IL-10, IL-12, IL-18, GMCSF, IFNgamma, TGFbeta and TNFalpha) and two housekeeping
      genes (ATPase and GADPH). We have used this assay to measure the constitutive
      expression of cytokine mRNA in MACS-purified CD4+ and CD8+ T lymphocytes from
      both lymphoid compartments.

PMID- 12072243
TI  - Activation of bovine peripheral blood gammadelta T cells for cell division and
      IFN-gamma production.
AB  - Bovine peripheral blood gammadelta T cells have been evaluated for effector
      function (IFN-gamma production) and clonal expansion in a variety of systems
      including following activation by mitogens, IL-12, and stimulation, through the T
      cell receptor (TCR) with anti-CD3 monoclonal antibody (mAb), a cell-bound
      molecule and a soluble antigenic extract. To evaluate cell division,
      carboxyfluorescein succinimidyl ester (CFSE) loading of cells and flow cytometric
      analysis were used, while IFN-gamma production was evaluated by intracytoplasmic
      staining. It was found that bovine gammadelta T cells produced IFN-gamma and
      clonally expanded when stimulated through the TCR/CD3 complex by a cell
      associated autologous molecule on monocyte, by bacterial components following in
      vivo sensitization of gammadelta T cells with a leptospira vaccine or by anti-CD3
      mAb. In addition, gammadelta T cells were activated efficiently for effector
      function but not clonal expansion by culturing with IL-12. In contrast,
      stimulation by Con A or PMA/ionomycin induced efficient replication but only low
      level IFN-gamma production which was not enhanced by the presence of IL-12. In
      several systems the amount of IFN-gamma produced per cell by gammadelta T cells
      was less than that produced by CD4 T cells in the same cultures.

PMID- 12072245
TI  - Mucosal immunology: overview and potential in the veterinary species.
AB  - A large part of the immune system is dedicated to protection from infection at
      mucosal surfaces. The concept of the common mucosal immune system has been
      investigated in several veterinary species where traffic of mucosally activated
      lymphocytes from induction to effector sites has been demonstrated. The dominant
      isotype found in secretions of the upper respiratory tract and gut of normal
      healthy and diseased animals is IgA. B lymphocytes have a relatively short half
      life and there is continuous production of IgA at these sites, which is achieved
      by constant secretion from T helper and epithelial cells of cytokines that are
      critical for B cell maturation and IgA secretion. Specific stimulation of mucosal
      immune responses using intranasal presentation of live and inactivated antigens
      (with adjuvants active at mucosal surfaces) has shown great promise for inducing
      protective immunity to respiratory pathogens.

PMID- 12072246
TI  - Induction of mucosal immune responses following enteric immunization with antigen
      delivered in alginate microspheres.
AB  - Oral immunization is the most effective way of inducing immune responses in the
      intestinal tract. Biodegradable microspheres have been used extensively for the
      delivery of antigens to the Peyer's patches (PPs) within the gut-associated
      lymphoid tissue (GALT). We evaluated various formulations of alginate
      microspheres for their capacity to induce mucosal immune responses in vivo.
      Multiple intestinal "loops" each containing a single PP, were surgically prepared
      in lambs. We have previously showed that PP in individual intestinal loops
      function as independent sites for the induction of immune responses. This animal
      model provides a system for directly comparing different antigen formulations
      within the same animal. Individual intestinal loops were injected with a model
      antigen, porcine serum albumin (PSA) encapsulated in three different formulations
      of alginate micropsheres. Three weeks after immunization, PSA-specific immune
      responses were assayed with antibody secreting cell (ASC) ELISPOT, lymphocyte
      proliferative responses (LPRs), IFN-gamma production and antibody secreted into
      intestinal loops. PSA encapsulated in alginate micropsheres or in saline induced
      humoral immune responses as indicated by the presence of numerous ASC. However,
      PSA-specific T-cell responses (LPR and IFN-gamma production) were not induced.

PMID- 12072247
TI  - Neutrophil migration in the lung, general and bovine-specific aspects.
AB  - Lung inflammation is often associated with sustained neutrophil migration into
      the lung tissue, causing undesired side effects, i.e. substantial damage of lung
      tissue and fibrin deposition, which hamper complete recovery. The need for
      additional anti-inflammatory treatment strategies focused attention on the
      function of cellular adhesion molecules (CAMs) on the leukocyte membrane, which
      guide migration of leukocytes across the endothelium to the site of inflammation.
      Recent data indicate that neutrophil migration in the lung is mediated by unique
      pathways, involving different CAM as compared to other organs. These pulmonary
      characteristics of neutrophil migration enable specific targeting of CAM for anti
      inflammatory treatment of pneumonia. In addition, the recent interest in
      intracellular signaling revealed that most CAM not only function in adhesion, but
      also play an important role in initiation of intracellular signal transduction
      and vice versa may be modulated by intracellular signaling molecules (ISMs). In
      this review, the mechanisms of neutrophil migration in the lung and the role of
      ISM with respect to CAM function are described in the context of potential anti
      inflammatory intervention strategies.

PMID- 12072248
TI  - Oral immunisation of pigs with fimbrial antigens of enterotoxigenic E. coli: an
      interesting model to study mucosal immune mechanisms.
AB  - The intestinal mucosal immune system can discriminate actively between harmful
      pathogenic agents and harmless food antigens resulting in different immune
      responses namely IgA production and oral tolerance, respectively. Recently, a pig
      model has been developed for studying intestinal mucosal immune responses in
      which F4 fimbrial antigens of enterotoxigenic Escherichia coli (F4 ETEC) are used
      as oral antigens. A unique feature of this model is that soluble F4 antigens can
      be administered to pigs which have a receptor for this fimbriae (F4R(+)) on their
      small intestinal villous enterocytes and pigs which do not have this receptor
      (F4R(-)). Oral administration of F4 to the F4R(+) pigs results in an intestinal
      mucosal immune response that completely protects the pigs against a challenge
      infection. In F4R(-) pigs such an intestinal mucosal immune response does not
      occur. However, a priming of the systemic immune system can be seen similar to
      the priming in pigs fed with the same dose of a food antigen, suggesting that F4
      in F4R(-) pigs behaves as a food antigen. The fact that different mucosal immune
      responses can be induced with soluble F4, makes it an interesting model to study
      mucosal immune mechanisms in the pig.

PMID- 12072249
TI  - Mucosal immunoadjuvant activity of the low toxic recombinant Escherichia coli
      heat-labile enterotoxin produced by Bacillus brevis for the bacterial subunit or
      component vaccine in pigs and cattle.
AB  - A gene encoding the mature Escherichia coli heat-labile enterotoxin (LT) lacking
      the nick site in the A subunit by deleting tripeptides was introduced in a vector
      pNH301 and expressed extracellularly as mutant molecule of holotoxin at high
      levels in Bacilus brevis HPD31-S5 of the host bacterium. The mucosal adjuvant
      activities of the produced mutant LT (mLT) preparation were studied in pigs and
      cattle. Intranasal immunization of pigs with the recombinant subunit vaccine of
      Erysipelothrix rhusiopathiae or the component vaccine of Bordetella
      bronchiseptica mixed with the mLT resulted in a substantial enhancement of both
      mucosal and serum-specific antibody levels. The immunized pigs were also
      protected when challenge-exposed intradermally with a highly virulent E.
      rhusiopathiae strain or challenge-exposed intranasally with a highly virulent
      strain of B. bronchiseptica. The mLT intranasally administered with recombinant
      intimin (an outer membrane adhesin) of E. coli O157:H7 also induced an elevation
      of IgA-specific antibody in the nasal secretion and saliva of calves as well as
      an elevation of IgG1-specific antibody level against the intimin in the sera and
      colostrum of cows. The three kinds tested protein antigens were poorly
      immunogenic when antigen administered intranasally alone. The mLT intranasally
      administered at a higher effective dose did not induce local adverse reactions or
      diarrhea in pigs and cattle. The present study demonstrates that the recombinant
      mLT produced using the B. brevis expression system might represent promising
      immunoadjuvants for the potential application of intranasal vaccines directed
      against infectious diseases in pigs and cattle.

PMID- 12072250
TI  - Early development of immune system in pigs.
AB  - Prenatal and early postnatal immune system development has been studied in
      minipigs. First leukocytes were observed in the yolk sac and fetal liver (FL) on
      the 17th day of gestation, the majority of them being SWC3(+). The colonization
      of the thymus (TH) with leukocytes was observed 21 days later. Two waves of fetal
      TH colonization with pro-T cells were deduced from the frequency of thymocyte
      subsets. Thymic B cells and immunoglobulin-secreting cells (Ig-SC) were studied
      by flow cytometry and ELISPOT, respectively. When the total numbers of fetal Ig
      SC were compared, the TH was identified as the main source of natural antibodies
      and the only site of IgA and IgG synthesis. In germ-free animals, the TH also
      represented the major site of IgG and IgA production and the number of Ig-SC was
      not influenced by colonization with microflora. FL and bone marrow were
      identified as primary B lymphopoietic sites. The phenotype of B precursors was
      characterized and pre-B II cells were shown to be the dominant mononuclear
      fraction between DG50 and DG105. In the periphery, relative proportions of
      lymphocyte subsets were determined. Studies in gnotobiotic piglets have revealed
      that the appearance of CD4(+)CD8(+) T cells and CD2(-) B cells is absolutely
      dependent on the contact of immune system with live viruses and bacteria,
      respectively.

PMID- 12072251
TI  - Switch recombination in fetal porcine thymus is uncoupled from somatic mutation.
AB  - Since fetal serum Ig isotype profiles suggested that IgG and IgA could be of de
      novo origin, we studied their transcription and secretion. IgM transcripts were
      present at 50 days of gestation in major fetal lymphoid tissues, IgG and IgA
      transcription was pronounced at 60 days in fetal thymus and both transcription
      and secretion in this organ increased in late fetal life. The CDR3 spectratype of
      thymic IgG and IgA transcripts was as polyclonal as that of IgM already at 70
      days in utero indicating a broad repertoire of switched B-cells. However, VDJs
      transcribed with the switched isotypes were not hypermutated as were those from
      immunized fetuses, indicating that switch recombination and somatic mutation are
      not coupled in utero in piglets. This finding and the fact that the oligoclonal
      IgA and IgM repertoires in a non-inductive site of the mucosal immune system
      (parotid gland) becomes polyclonal in piglets reared germ-free, suggest that
      initial expansion of switched B-cells in fetal and neonatal piglets is not driven
      by environmental antigen. Our findings collectively suggest that all IgA and IgM
      may result from de novo synthesis while some IgG probably results from selective
      transport. The latter is consistent with the gradual decline in serum IgG
      concentration in germ-free isolator piglets and the expression of FcRn in the
      porcine placenta.

PMID- 12072252
TI  - Postnatal development of leukocyte subset composition and activity in dogs.
AB  - The aim of the presentation is to summarise our data on the counts and activity
      of circulating canine leukocytes at birth and on their changes in the first 3
      months of life. On day 1, neutrophil counts were almost three times higher than
      lymphocyte counts. During the first week of life, a decrease of neutrophil and an
      increase of lymphocyte counts, resulting in a predominance of lymphocytes, were
      observed. Neutrophil counts reached values comparable with those in adults in 1
      month. Lymphocyte counts were higher than those in adults during the first 3
      months. From birth to the age of 3 months, the phagocytic activity of neutrophils
      was nonsignificantly higher than in young adults. When compared with adults, the
      peripheral blood of new-born pups contained a lower proportion of T lymphocytes
      (detected by CD3 and CD5 markers), with a very low percentage of CD8(+) cells and
      a higher proportion of CD21(+) B lymphocytes. The counts of individual subsets
      levelled out during the first 3 months of life, although the proportion of
      CD21(+) B cells remained higher all the time. Lymphocytes of new-born pups were
      able to respond to nonspecific mitogen stimulation. Spontaneous proliferation in
      vitro was higher during the first week of life. Although in vitro stimulation of
      lymphocytes with Concanavalin A in some pups was comparable with that of adult
      dogs, mean activity was weaker. Pups with zero or very low levels of maternal
      antibodies were able to develop specific immune responses to a parvovirus antigen
      as early as at 2 weeks of age. On the basis of these data, we assume that pups
      are born with an immune system that can respond to external stimuli. Nevertheless
      its development continues in the postnatal period and some parameters differ from
      adult values for at least 3 months after birth.

PMID- 12072254
TI  - Delayed anti-kappa response in kappa-deficient mice after neonatal, oral
      immunization with kappa-containing IgG.
AB  - Antibody responses to kappa (kappa)-light (L) chain are absent in normal
      (Ckappa+/+) animals because of tolerance due to the abundance of kappa-L chains
      expressed on more than 95% of all B cells and serum Ig.When heterozygous kappa
      sufficient (Ckappa+/-) females are bred with homozygous kappa-deficient (Ckappa-/
      ) males, half of their offspring will become kappa-deficient but have received
      kappa-L chain containing maternal Ig, mainly IgG and IgA, through placental and
      intestinal transmission. The kappa-containing maternal Ig persists for more than
      2 months in the circulation of the offspring. Starting from weeks 15 to 20 of
      age, a spontaneous antibody response towards the maternal kappa-L chains can be
      recorded. The time of onset, as well as the magnitude of the responses differ
      among individuals of the same litter. Invariably, once a response has been
      initiated, it transits into an IgG-type of response, which upon injection with
      kappa-containing protein shows the features of a secondary type of immune
      response.

PMID- 12072253
TI  - Localization of the sheep FcRn in the mammary gland.
AB  - Among the multiple functions, which have been identified for the neonatal Fc
      receptor (FcRn), we study its role in the IgG transport in the mammary gland
      during the colostrum formation. For this reason, we have obtained several mammary
      gland biopsies from a pregnant sheep around parturition. The presence of the FcRn
      heavy chain mRNA was detected exclusively in the acinar and ductal epithelial
      cell by in situ hybridization (ISH). We detected strong signal in samples
      harvested 24 and 10 days prepartum; however, in samples we collected postpartum
      was barely detectable. Immunohistochemistry confirmed our ISH data. The cytoplasm
      of the epithelial cells of the acini and ducts in the mammary gland biopsies
      stained homogeneously before parturition, although a remarkable difference was
      observed in the pattern after lambing. The signal indicated uneven distribution
      of the FcRn alpha chain in the epithelial cells 1 and 5 days postpartum, since
      the apical sides of the epithelial cells were highlighted. The presence of the
      FcRn in the acinar and ductal epithelial cells and the obvious change of its
      distribution before and after parturition suggest that FcRn plays an important
      role in the IgG transport during colostrum formation. FcRn expression was also
      found in the lamb duodenal crypt epithelial cells, which have been previously
      demonstrated to secrete IgG1 in newborn ruminants, suggesting secretory role of
      the FcRn in ruminant epithelial cells.

PMID- 12072255
TI  - B cell development in gut associated lymphoid tissues.
AB  - B lymphocyte development can occur in a variety of anatomical sites. While
      typically considered to be a process that occurs in the bone marrow throughout
      life, it is becoming clear that gut associates sites of B cell development are
      critically important in many species of veterinary importance. Among these sites,
      the bursa of Fabricius in chickens and the ileal Peyer's patches of sheep are
      among the best studied. In these organs, it has become clear that many of the
      properties associated with B cell development in rodent and primate bone marrow
      do not apply. Thus while bone marrow B cell development typically involves an
      ongoing maturation of mature B cells from immature B lineage precursors that lack
      the expression of a surface immunoglobulin complex, gut associated lymphoid
      tissues (GALTs) may be colonized by a single wave of precursor cells during
      embryo development. Nonetheless, molecular analysis of the requirements for B
      lymphocyte development in GALTs reveals some striking parallels with requirements
      identified for B cell development in bone marrow. This article will discuss
      differences between B cell development in the bone marrow and GALTs and recent
      evidence emerging that yields insights into how these processes are regulated.

PMID- 12072256
TI  - B cell development and VDJ rearrangement in the fetal pig.
AB  - Hematopoietic activity of the swine has been documented in three phases during
      fetal ontogeny. The hematopoietic system develops first in the yolk sac, then in
      fetal liver and finally in the bone marrow. Using flow cytometry (FCM) and
      molecular biological techniques we show that B-cell lymphogenesis and the
      appearance of B cells follows a pattern. First, VDJ rearrangement occurs at the
      20th day of gestation (DG20) in the yolk sac at a time when light chain
      transcription is absent. Next, B-cell lymphogenesis is detected at DG30 in the
      fetal liver. Thereafter, bone marrow becomes the major B lymphopoietic organ
      (DG45). In yolk sac and fetal liver, more than 90% of the VDJ rearrangements were
      in-frame but expression of micro heavy chain could not be clearly detected by
      FCM. However, cells with a putative phenotype of B-cell precursors are present.
      These cells express high levels of MHC class II (SLA-DR) and low levels of CD2
      and CD25. CDR3 length analysis (spectratyping) indicates that the heavy chain
      repertoire is oligoclonal at this time with large inter-animal variations.
      Consistent with our earlier reports, fetal VDJ rearrangements are not mutated and
      there is no evidence for an age-dependent increase in TdT activity or a change in
      V(H) and D(H) usage from those used by B-cells formed in the yolk sac or fetal
      liver. However, our findings indicate major differences in the regulatory
      environment and/or selective pressures in yolk sac and fetal liver versus bone
      marrow. In contrast with the yolk sac and fetal liver, the proportion of in-frame
      VDJ rearrangements in the bone marrow correspond to a value indicative of random
      recombination.

PMID- 12072258
TI  - Immune dysregulation in atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans and dogs
      with comparable clinical features. Comparative studies of immunological events in
      the pathogenesis of AD may contribute to understanding of the disease in dogs and
      to development and evaluation of immunomodulatory strategies of relevance to both
      species.Both allergen-specific as well as non-specific mechanisms contribute to
      the disease development. AD skin lesions are proposed to be initiated by
      activation of allergen-specific Th2-type cells, potentially influenced by local
      cutaneous factors. In the chronic stage of skin lesions reactivity may change
      into a Th1-type, e.g. driven by eosinophil derived IL-12. Analyses of these
      processes in course of time were performed in both spontaneous as well as in
      experimentally induced lesions (i.e. atopy patch test (APT) lesions). In the
      present paper, the immunological events as reported for human and canine AD are
      summarized and compared.

PMID- 12072257
TI  - Novel insight into antibody diversification from cattle.
AB  - The bovine preimmune repertoire develops in the absence of maternal antibodies
      due to the placental barrier formed by syndesmochorial type of placenta. The
      limited germline sequence diversity, both at the heavy and light chain loci,
      imposes constraints on generation of combinatorial diversity in cattle. The
      cattle, thus, must employ other strategies for antibody diversification. Analysis
      of VDJ rearrangements in adult cattle have led identification of generation of
      large IgM antibody molecules that may have an exceptionally long CDR3H region (up
      to 61 amino acids). The IgM antibodies with an exceptionally long CDR3H are
      indeed functional as some of these recognize structurally dissimilar antigens.
      The antibody diversification in cattle involves generation of an exceptionally
      long CDR3H in addition to point somatic mutations.

PMID- 12072259
TI  - Intranasal peptide-induced peripheral tolerance: the role of IL-10 in regulatory
      T cell function within the context of experimental autoimmune encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune
      disease commonly employed as a model for multiple sclerosis. Extensive studies
      have demonstrated that EAE may be prevented or ameliorated by the intranasal
      administration of soluble peptides representing encephalitogenic epitopes. There
      is increasing evidence that this peptide administration may function via the
      generation of regulatory cells. The mechanism of action of these cells remains
      controversial and it seems likely that it may vary between experimental models.
      At present the majority of work on regulatory cells has centred on characterising
      naturally occurring regulators, or those generated artificially ex vivo, and less
      is known about induced regulatory cells produced following peptide
      administration. This report aims to briefly outline the evidence for the
      existence of natural regulatory T cells and to introduce the sub-types of induced
      regulatory T cells now recognised. In several of these regulatory cell systems
      investigated to date, interleukin-10 (IL-10) has been shown to be important in
      cell function. This has not been directly investigated in a model employing
      peptide therapy to induce peripheral tolerance, hence the purpose of this study
      was to investigate the role of IL-10 in the generation of these regulatory cells.
      This work has employed both a TCR transgenic mouse system, for predominantly in
      vitro studies of cell function, and an IL-10 knock-out mouse strain to
      investigate in vivo disease protection. The results summarised in this report
      demonstrate that IL-10 is fundamentally important in the generation of disease
      protection following intranasal peptide therapy.

PMID- 12072260
TI  - Allergic pulmonary and ocular tissue responses in the absence of serum IgE
      antibodies (IgE) in an allergic dog model.
AB  - Allergen-specific serum IgE may be insensitive as a marker for IgE-mediated
      reactions at the mucosal level. Five of six atopic beagle dogs developed high
      ovalbumin (OVA)-specific serum IgE levels after sensitization. This study aimed
      to show that these dogs still express allergen-specific IgE at the pulmonary and
      ocular mucosal levels and in the skin even when corresponding serum IgE was below
      the detection limit. When serum IgE levels were negative, all dogs exhibited
      allergic reactions at the tissue level. Specifically, they displayed positive
      ocular reactions after an ocular OVA challenge. After airway challenge with
      aerosolized OVA, five out of six animals reacted with decreased compliance and
      increased resistance of the lungs. Furthermore, an eosinophilia in the
      bronchoalveolar lavage fluid (BALF) was observed. Four weeks after the last
      exposure to OVA, IgE-positive BALF cells were seen in all animals. Six weeks on,
      all dogs still displayed positive skin reactions to OVA. This indicates that not
      only skin testing but also detection of ocular and pulmonary allergic tissue
      reactions including cell-bound IgE in BALF can serve as more sensitive and
      lasting surrogate markers of hypersensitivity in the allergic dog model than
      detection of allergen-specific serum IgE levels.

PMID- 12072261
TI  - T-helper 1, T-helper 2 and immunosuppressive cytokines in canine atopic
      dermatitis.
AB  - Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human
      atopic dermatitis is associated with T-helper (Th) 2 type responses, although Th1
      cytokines are present in chronic lesions. This study used semi-quantitative
      reverse transcriptase polymerase chain reactions to determine the expression of
      gene transcripts for immunosuppressive cytokines (transforming growth factor beta
      [TGFbeta] and interleukin [IL]-10), Th2 type cytokines (IL-4 and IL-6) and Th1
      type cytokines (interferon gamma [IFNgamma], tumour necrosis factor alpha
      [TNFalpha], IL-2 and IL-12) in lesional atopic, non-lesional atopic and healthy
      canine skin. Canine atopic dermatitis was associated with over-expression of IL-4
      mRNA and reduced transcription of TGFbeta compared to healthy skin (ANOVA,
      p<0.05). Higher levels of IFNgamma, TNFalpha and IL-2 mRNA were seen in lesional
      compared to non-lesional and healthy skin (p<0.05). There were no significant
      differences in IL-10, IL-6 or IL-12 transcription. This is the first report to
      demonstrate that canine atopic dermatitis is associated with over-production of
      IL-4 and under expression of TGFbeta.

PMID- 12072262
TI  - A novel model for equine recurrent airway obstruction.
AB  - Equine recurrent airway obstruction (RAO; a term combining both chronic
      obstructive pulmonary disease (COPD) and summer pasture associated obstructive
      pulmonary disease (SPAOPD)) is one of the most common equine respiratory diseases
      with up to 50% of horses affected worldwide. The etiopathogenesis of RAO is
      unknown although pulmonary hypersensitivity to inhaled mold antigens may be
      involved. Recent work in our laboratory demonstrating elevated levels of IL-4 and
      IL-13 mRNA in the airways and peripheral blood of horses with RAO is consistent
      with an atopic component to RAO. Little is known regarding the earliest phases of
      RAO in horses. Here we describe the development of a novel airway model for
      equine RAO that utilizes ovalbumin-coated polystyrene beads for airway
      sensitization and challenge. Aerosol challenge of sensitized ponies with OVA
      coated microbeads resulted in decreased airway compliance, increased percentage
      of lymphocytes and neutrophils in the bronchoalveolar lavage fluid, and evidence
      of a Th2 cytokine response in the bronchoalveolar cells. These results suggest
      that this approach may be useful in describing the initial stages of RAO
      development in the horse.

PMID- 12072263
TI  - Where do we go in protection against pathogens?
AB  - A few reflections are made on the future strategies and approaches for combating
      infectious diseases of livestock, keeping into consideration public concern on
      food quality and availability. The policy of eradication of pathogens/diseases
      instead of vaccination has rendered livestock naive to certain pathogens and as a
      consequence susceptible to epidemic outbreaks, even more so as we have to
      conclude that outside attack is quite often difficult to control. Therefore,
      immunoprophylactic measures in livestock remain top priority and will in the
      future focus more on the induction of mucosal immunity and the activation of
      innate immunity.

PMID- 12072264
TI  - Orf virus immuno-modulation and the host immune response.
AB  - Orf virus encodes a range of immuno-modulatory genes that interfere with host
      anti-virus immune and inflammatory effector mechanisms. The function of these
      reflects the pathogenesis of orf. The orf virus interferon resistance protein
      (OVIFNR) and virus IL-10 (vIL-10) inhibit interferon production and activity. In
      addition the vIL-10 suppresses inflammatory cytokine production by activated
      macrophages and keratinocytes. The virus GM-CSF inhibitory factor (GIF) is a
      novel virus protein that binds to and inhibits the biological activity of GM-CSF
      and IL-2. Together, these immuno-modulators target key effector mechanisms of
      host anti-virus immunity to allow time for virus replication in epidermal cells.

PMID- 12072266
TI  - Leukocyte endothelial cell interactions in pig to human organ xenograft
      rejection.
AB  - In cases where antibody- and complement-mediated hyperacute rejection (HAR) of
      vascularized organ xenografts has been prevented, acute vascular rejection (AVR)
      and acute T cell-mediated rejection (ACR) cause graft destruction. Infiltration
      of leukocytes (innate and graft-primed T cells) into the graft execute the latter
      two rejection modalities. The leukocyte extravasation process, which is a
      prerequisite for graft infiltration, is governed by adhesion molecules, including
      the selectin, integrin and immunoglobulin protein families, and the chemokine
      protein family. The compatibility between porcine endothelial cell and human
      leukocyte adhesion molecules was investigated in dynamic adhesion and static
      transendothelial migration assays. The effect of human anti-pig antibodies on
      human leukocyte adhesion to, and transendothelial migration across, porcine
      endothelium was assessed under dynamic and static conditions, respectively. In
      contrast to previously published results, no difference in the ability of
      neutrophils to adhere to pig and human endothelium was observed. Furthermore, no
      evident quantitative or qualitative differences in the capacity of human and
      porcine endothelium to support transendothelial migration of human leukocytes (T,
      B and natural killer (NK) cells, monocytes, and neutrophils) could be detected.
      The presence of human anti-pig antibodies (Abs) modulated the migration of
      leukocytes across porcine endothelium, as well as neutrophil adhesion to porcine
      endothelium under conditions of flow. Antibodies specific for pig endothelial
      adhesion molecules can potentially be used as species (graft)-specific
      immunosuppressive reagents in order to prevent cellular organ xenograft
      rejection.

PMID- 12072265
TI  - IFN-gamma diagnostic tests in the context of bovine mycobacterial infections in
      Belgium.
AB  - In countries where cattle tuberculosis caused by Mycobacterium bovis (Mbov) and
      paratuberculosis caused by Mycobacterium avium subsp. paratuberculosis (Mptb) are
      present, testing strategies for the Mbov eradication have to discriminate between
      these two infections. Present indirect tests are based on the analysis of the
      specific cellular immune response (DTH, IFN-gamma) against crude mycobacterial
      antigens (avian and bovine PPD). In this study, we compared the evolution of the
      IFN-gamma responses of animals experimentally infected with Mbov, Mptb, or
      inoculated with Mycobacterium phlei. Mbov inoculation induced a strong IFN-gamma
      response that allows rapid classification of the status of the animals following
      interpretation criteria set up by us. Experimental inoculation with M. phlei
      induced sensitisation to mycobacterial antigens as detected by the IFN-gamma test
      but these reactions were of short duration, therefore, repeated testing allows us
      to define these animals as aspecific reactors. IFN-gamma response induced after
      oral inoculation of calves with Mptb was of low intensity and ratio of responses
      measured against avian versus bovine PPD did not allow a clear diagnostic at
      least for the six first month of infection.

PMID- 12072267
TI  - Functional expression of a bovine major histocompatibility complex class I gene
      in transgenic mice.
AB  - Major histocompatibility complex (MHC) class I restricted cellular immune
      responses play an important role in immunity to intracellular pathogens. By
      binding antigenic peptides and presenting them to T cells, class I molecules
      impose significant selection on the targets of immune responses. Candidate
      vaccine antigens for cellular immune responses should therefore be analysed in
      the context of MHC class I antigen presentation. Transgenic mice expressing human
      MHC (HLA) genes provide a useful model for the identification of potential
      cytotoxic T lymphocyte (CTL) antigens. To facilitate the analysis of candidate
      CTL vaccines in cattle, we have produced transgenic mice expressing a common
      bovine MHC (BoLA) class I allele. The functional BoLA-A11 gene, carried on a 7 kb
      genomic DNA fragment, was used to make transgenic mice by pronuclear
      microinjection. Three transgenic mouse lines carrying the BoLA-A11 gene were
      established. Expression of the BoLA-A11 gene was found in RNA and the A11 product
      could be detected on the surface of spleen and blood cells. Functional analysis
      of the A11 transgene product, and its ability to act as an antigen presenting
      molecules in the mouse host will be discussed.

PMID- 12072268
TI  - Candidate genes for resistance to Salmonella enteritidis colonization in chickens
      as detected in a novel genetic cross.
AB  - Salmonellosis is a zoonotic disease that is problematic for both animal
      production and food safety. A novel genetic cross, named the Iowa Salmonella
      response resource population (ISRRP), was established to elucidate the genetic
      control of resistance to Salmonella enteritidis (SE) colonization in young
      chicks, to characterize unique resistance alleles, and to estimate gene
      interaction effects. Outbred broiler sires were mated with dams of diverse,
      highly inbred, light-bodied lines to produce an F(1) generation that was
      informative for all heterozygous alleles of the sires. Mating F(1) sires back to
      dams of the corresponding inbred line produced a backcross generation. To mimic
      the natural route of exposure and thus afford the opportunity to investigate
      mucosal immunity, pathogenic SE were inoculated into the esophagus of day-old
      chicks. After 1 week, the SE colonizing the cecal lumen and the spleen were
      enumerated. Candidate genes were selected for analysis based upon one of the two
      criteria. Functional candidates were genes with reported activity related to the
      tested traits. Positional candidates were genes mapped near microsatellites that
      were linked, in other phases of this project, with antibody levels to SE vaccine.
      Broiler sire alleles of the MHC class I, NRAMP1, PSAP, and IAP1 genes showed
      association with SE colonization in the F(1) generation of this novel disease
      resistance resource population.

PMID- 12072269
TI  - Survival tactics of M. paratuberculosis in bovine macrophage cells.
AB  - Mycobacterium paratuberculosis (M. paratuberculosis) is a facultative
      intracellular bacterium with the ability to survive and proliferate inside the
      vesicles of macrophage cells. How M. paratuberculosis and other mycobacteria
      survive in this hostile environment is not well understood. Present research
      findings can be divided into three possibilities: (1) mycobacteria may interfere
      with host protein expression and trafficking to stop vesicle maturation, (2)
      mycobacteria may express proteins that interfere with macrophage activation in a
      more direct manner, or (3) mycobacteria may enter macrophages in such a way as to
      avoid the normal process of activation via Toll-like receptors and other, as yet
      unknown mechanisms. Research thus far has predominately centered on possible
      macrophage/mycobacteria protein interactions. To more completely define how
      mycobacteria interfere with the process of phagosome maturation our group has
      recently taken a functional genomics approach, allowing the macrophage to "tell"
      us what host genes may be affected by phagocytosis of mycobacteria. We used DDRT
      PCR to examine differences in macrophage cell gene expression during phagocytosis
      of E. coli and M. paratuberculosis. Macrophage cells not exposed to any
      phagocytosis target and in the process of phagocytosing latex beads were used as
      negative and positive controls, respectively. To date, we have identified 380
      DDRT-PCR amplicons corresponding to transcripts whose expression profiles appear
      to be altered during the general process of phagocytosis. Dot-blot and Northern
      blot hybridizations with a subset of these amplicons were performed to confirm
      results observed with DDRT-PCR. Our preliminary results indicate that macrophage
      gene expression profiles change dramatically following phagocytosis and that gene
      expression profiles following phagocytosis of M. paratuberculosis are different
      than those following phagocytosis of E. coli or latex beads.

PMID- 12072270
TI  - Genomic sequencing of the bovine T cell receptor beta locus.
AB  - The T cell, which plays an integral role in the coordination of the immune
      system, has a heterodimer receptor (TCR) that can exist in one of the two forms:
      alpha/beta or gamma/delta. Cells displaying the gamma/delta TCR comprise less
      than 5% of T cell populations in humans and mice. In the bovine system, however,
      gamma/delta populations can reach as high as 60%. Differences in T cell
      populations make the bovine system an excellent candidate for genomic TCR
      sequencing and multi-species comparisons. In an effort to characterize the bovine
      TCR loci, a genomic library was screened for the beta TCR gene. A shotgun
      sequencing library was constructed and preliminary analysis demonstrates that the
      organization of the bovine TCR beta constant regions is different from both
      humans and mice. The bovine beta locus appears to have a third constant region.
      Overall, the genomic characterization of the bovine TCR genes will provide
      insight into the evolution of T cell receptor.

PMID- 12072271
TI  - The concept of sickness behavior: a brief chronological account of four key
      discoveries.
AB  - Neurons do not have receptors to detect bacteria or viruses, yet the presence of
      these microorganisms can cause a sickness behavior syndrome that includes, e.g.,
      fever, anorexia, and lethargy. Because the immune system has receptors capable of
      detecting these non-cognitive stimuli, how the immune system transmits a message
      to the brain has been studied to understand why behavior is altered in sick
      animals. The focus has been on several cytokines secreted by leukocytes; these
      include interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF
      alpha). These cytokines are secreted by activated mononuclear phagocytic cells,
      and numerous studies show that both peripheral and central injection of IL-1beta,
      IL-6, and TNF-alpha induce sickness behavior. Moreover, these cytokines and their
      receptors are present in the brain and inhibiting the secretion of cytokines or
      blocking their receptors in the brain blocks or abrogate the behavioral responses
      induced by inflammatory stimuli. Because the sickness behavior syndrome modulates
      the immune system and enhances recovery, the interplay between the immune system
      and central nervous system is an essential part of the overall host defense
      against pathogenic microorganisms. The purpose of this brief paper is to provide
      a chronological description of four critical advances that have led to the
      current understanding of how the immune system communicates with the brain to
      induce sickness behavior. Results from several key studies will be discussed,
      which showed that: (1) sickness behavior is a motivational state; (2) sickness
      behavior is a well-organized adaptive response to infection; (3) cytokines
      produced by activated leukocytes induce sickness behavior; and (4) cytokines
      transmit messages from the periphery to the brain using humoral and neural
      pathways.

PMID- 12072272
TI  - Does cortisol bias cytokine production in cultured porcine splenocytes to a Th2
      phenotype?
AB  - Glucocorticoids are reported to bias the production of cytokines from a type 1 to
      a type 2 phenotype. However, this dogma has been advanced largely from studies
      utilizing potent glucocorticoid analogs, particularly dexamethasone (DEX).
      Although studies utilizing DEX certainly have clinical and pharmacological
      relevance, DEX is probably not the best glucocorticoid for studies designed to
      evaluate the interaction and regulation of endogenous corticosteroids with immune
      cells in vivo in the domestic pig. Functional measures of immune suppression
      suggest that the pig is relatively resistant to DEX. Furthermore, type II
      corticosteroid receptors exclusively bind DEX with high affinity, whereas type I
      receptors, the so-called mineralocorticoid receptors, have a higher affinity for
      cortisol. In addition, DEX is not bound by serum binding proteins as are
      endogenous corticosteroids. These issues prompted us to revisit glucocorticoid
      regulation of type 1 and type 2 cytokines in cultured pig splenocytes and to test
      the broad hypothesis that cortisol biases cytokine production in favor of a Th2
      response. We evaluated interferon gamma (IFNgamma) (also interleukin 2 (IL-2) in
      one experiment) and interleukin 10 (IL-10) as representative Th1 and Th2
      cytokines, respectively. Furthermore, we evaluated macrophage migration
      inhibitory factor (MIF) because it is reported to be an essential factor in T
      cell activation; it is also upregulated by glucocorticoids and reported to be a
      product of Th2 lymphocytes. In general, both IFNgamma and IL-10 were sensitive to
      cortisol inhibition early in culture. However, IFNgamma ultimately escaped
      cortisol inhibition, whereas IL-10 continued to be substantially suppressed by
      high physiological concentrations of cortisol. Similarly, MIF mRNA could be
      suppressed by cortisol, but only when cortisol was added to cultures after ConA
      (concanavalin A) stimulation of splenocytes. So, taken together, our studies do
      not support the hypothesis that cortisol favors a Th2 cytokine profile in
      cultured pig splenocytes.

PMID- 12072273
TI  - Effects of dexamethasone on distribution and function of peripheral mononuclear
      blood cells in pneumonic calves.
AB  - Experimental pneumonic pasteurellosis was used in 30 Holstein calves to compare
      the effects on the immune response of different treatments: antibiotics alone or
      antibiotics in combination with either steroidal (SAID) or non-steroidal anti
      inflammatory drugs (NSAID). Clinical parameters and the effect of treatments on
      the mitogen-induced proliferation of peripheral mononuclear blood cells (PMBCs)
      and on their distribution were evaluated. Calves in all three treated groups
      showed rapid improvement, but clinical signs were less marked in both groups
      receiving anti-inflammatory drugs. Limited difference in the effect on the immune
      system of treatments was observed. No inhibition of lymphocytes proliferation was
      detected in these experimental conditions in the dexamethasone (DM)-treated
      group. There was no variation among groups for the CD4+, CD5+, CD8+ and CD21+
      populations. The only noteworthy change was a transient increase in the
      percentage of the monocyte population (CD14+) in the DM-treated group compared to
      the group treated with NSAID.

PMID- 12072274
TI  - Neuroendocrine-immune interactions in fish: a role for interleukin-1.
AB  - Bi-directional communication between the hypothalamus-pituitary-adrenal (HPA)
      axis and the sympathetic nervous system with the immune system is crucial to
      ensure homeostasis. Shared use of ligands and especially receptors forms a key
      component of this bi-directional interaction. Glucocorticoids (GC), the major end
      products of the HPA-axis differentially modulate immune function. Cytokines,
      especially interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6), ensure immune signalling to the neuroendocrine system. In
      addition, hormones from leukocyte origin such as corticotropin-releasing hormone
      (CRH), adrenocorticotropic hormone (ACTH) and beta-endorphin, as well as
      centrally synthesised and secreted cytokines, contribute to the communication
      network. In teleost fish cortisol is the major product of the hypothalamus
      pituitary-interrenal (HPI)-axis which is the teleost equivalent of the HPA-axis.
      Moderate and substantial increases in cortisol during stressful circumstances
      negatively affect B-lymphocytes, whereas rescue of neutrophilic granulocytes may
      support innate immunity. Recent elucidation of lower vertebrate cytokine
      sequences has facilitated research into neuroendocrine-immune interactions in
      teleosts and the first evidence for a significant function of interleukin-1 in
      the bi-directional communication is discussed.

PMID- 12072275
TI  - Summary of the Comparative Immunoglobulin Workshop (CIgW) on immunoglobulins
      (Igs) and Fc receptors.

PMID- 12072277
TI  - Looking back and looking forward: The International Veterinary Immunology
      Symposium at Fifteen.

PMID- 12072276
TI  - New technologies for studying immune regulation in ruminants.
AB  - There remains a great need for the development of reagents and techniques to
      study immune regulation in ruminants. These tools are fundamental to our
      understanding of the mechanisms of immune modulation and underpin the rational
      design of disease control strategies in livestock. Technological advances in
      molecular biology have resulted in the development of a new range of techniques
      to measure and quantify gene expression in normal and disease states. However,
      the ability to measure protein expression, produce proteins (usually in
      recombinant form) and to block receptor-ligand interactions remains essential for
      elucidating the function of the molecules of interest. The aims of this workshop
      were to look at the current status of reagents for studying ruminant immunology,
      the prospects for future developments, and also to discuss reagents availability
      between different groups worldwide.

PMID- 12072278
TI  - Alexis Carrel's legacy: visionary of vascular surgery and organ transplantation.

PMID- 12072279
TI  - A 50-year retrospective: cell-mediated immunity and the major histocompatibility
      complex.

PMID- 12072280
TI  - Transplantation of green fluorescent hepatic stellate cells into rat livers.

PMID- 12072281
TI  - Allogeneic heart graft rejection in mice: correlation between mononuclear cell
      infiltration and extracellular matrix deposition.

PMID- 12072282
TI  - Pentoxifylline inhibits perforin-dependent PBMC cytotoxic activity.

PMID- 12072283
TI  - Vaccinia virus complement control protein inhibits hyperacute xenorejection.

PMID- 12072284
TI  - Reduction of ischemia-reperfusion injury in parenchymal and nonparenchymal liver
      cells by donor treatment with DL-alpha-tocopherol prior to organ harvest.

PMID- 12072285
TI  - Alpha-tocopherol in the hypothermic preservation of the rat small bowel: a
      functional study.

PMID- 12072286
TI  - Determination of apoptotic cells in kidneys from non-heart-beating donors and
      heart-beating donors using the TUNEL assay: a limited immunohistochemical method?

PMID- 12072287
TI  - An experimental estimation of the maximum period of liver preservation using
      dielectric parameters.

PMID- 12072288
TI  - Evaluation of the vascular permeability after 12-hour preservation of rabbit
      lungs in HTK solution.

PMID- 12072290
TI  - Transient cold preservation alone stimulates tumor necrosis factor-alpha gene
      expression in a model of rat syngeneic lung transplantation.

PMID- 12072289
TI  - The effect of Collin's, Euro-Collin's, and University of Wisconsin solutions on
      the function of isolated proximal straight tubules.

PMID- 12072291
TI  - Reduced reperfusion injury by glycine in a porcine liver transplantation model
      with non-heart-beating donors.

PMID- 12072292
TI  - Importance of calcium during hypothermic myocardial preservation with standard
      and modified UW solutions.

PMID- 12072293
TI  - Combined immunosuppression with cyclosporine, rapamycin, and mycophenolate
      mofetil controls rejection with minimal nutritional impact in experimental small
      intestinal transplantation.

PMID- 12072294
TI  - Influence of a novel rapamycin analogon SDZ RAD on endothelial tissue factor and
      adhesion molecule expression.

PMID- 12072295
TI  - Prolongation of fully allogeneic skin graft survival in the rat by combined
      administration of costimulatory blockade and sirolimus.

PMID- 12072296
TI  - Differential modulation of synthesis of human IL-1 beta and IL-1 receptor
      antagonist by cyclosporin A.

PMID- 12072297
TI  - TAK-603, new rheumatic drug, inhibits rat mixed lymphocyte reactions and
      prolonges rat skin allograft survival.

PMID- 12072298
TI  - Factors influencing contralateral renal hypertrophy after living donor
      nephrectomy.

PMID- 12072299
TI  - The domino procedure: a new phase in the saga of kidney transplantation in India.

PMID- 12072300
TI  - Influence on family psychodynamics on spousal kidney transplantation.

PMID- 12072301
TI  - Accurately simple estimation of glomerular filtration rate in kidney transplant
      patients.

PMID- 12072302
TI  - Prognostic significance of serum cystatin c concentrations in renal transplant
      recipients: 5-year follow-up.

PMID- 12072303
TI  - Renal function, homocysteine, and other plasma thiol concentrations during the
      postrenal transplant period.

PMID- 12072304
TI  - Effect of pregnancy on renal graft function and maternal survival in renal
      transplant recipients.

PMID- 12072305
TI  - Role of immunosuppressive drugs in the development of tissue-invasive
      cytomegalovirus infection in renal transplant recipients.

PMID- 12072306
TI  - Direct visualisation of cytomegalovirus-specific CD8+ T cells in renal transplant
      recipients.

PMID- 12072307
TI  - Atypical generalized zoster with suspicious esophageal involvement and early
      relapse in an adult renal transplant recepient.

PMID- 12072308
TI  - Monotherapy with the anti-CD20 monoclonal antibody rituximab in a kidney
      transplant recipient with posttransplant lymphoproliferative disease.

PMID- 12072309
TI  - FK 506-induced fulminant leukoencephalopathy after kidney transplantation: case
      report.

PMID- 12072310
TI  - Aspects of cyclosporine A toxicity in the development of coronary artery disease
      in transplant recipients.

PMID- 12072312
TI  - Donor graft lithiasis in kidney transplantation.

PMID- 12072311
TI  - Rectal cancer following a kidney-pancreas transplant.

PMID- 12072313
TI  - Case report: living related renal transplantation with a donor kidney with
      pelviureteric junction obstruction using an Anderson-Hynes pyeloplasty.

PMID- 12072314
TI  - Loss of heterozygosity in tertiary hyperparathyroidism.

PMID- 12072315
TI  - Avascular acetabular necrosis in a renal transplant patient.

PMID- 12072316
TI  - Lower gastrointestinal tract hemorrhage due to ectopic pancreatic tissue in a
      renal transplant recipient: a case report.

PMID- 12072318
TI  - Biliary reconstructions in 150 orthotopic liver transplantations: an experience
      with three techniques.

PMID- 12072317
TI  - Impact of graft rearterialization after auxiliary partial orthotopic liver
      transplantation in the treatment of acute liver failure.

PMID- 12072319
TI  - The left gastric vein as an alternative to portal reconstruction in orthotopic
      liver transplantation.

PMID- 12072320
TI  - Restorative proctocolectomy following orthotopic liver transplantation for
      primary sclerosing cholangitis.

PMID- 12072321
TI  - Propofol to control intracranial pressure in fulminant hepatic failure.

PMID- 12072322
TI  - Prediction of survival outcome of ICU patients awaiting orthotopic liver
      transplantation.

PMID- 12072324
TI  - Immunosuppression in living related and living unrelated liver transplantation.

PMID- 12072323
TI  - Long-term follow-up after liver transplantation for blunt hepatic trauma.

PMID- 12072325
TI  - Analysis of initial poor graft function after orthotopic liver transplantation:
      experience of an australian single liver transplantation center.

PMID- 12072327
TI  - Psychosocial prediction of abstinence from ethanol in alcoholic recipients
      following liver transplantation.

PMID- 12072326
TI  - Outcome of liver transplantation in Hispanics versus non-Hispanics: is there a
      difference?

PMID- 12072328
TI  - Staggered immunosuppression with the interleukin-2 receptor antagonist daclizumab
      combined with tacrolimus, prednisolone, and mycophenolate mofetil after
      orthotopic liver transplantation: a pilot efficacy and safety study.

PMID- 12072329
TI  - Recurrence of Langerhans cell histiocytosis in the graft after liver
      transplantation in adults.

PMID- 12072330
TI  - Epithelioid hemangioendothelioma of the liver: case report and review of the
      literature.

PMID- 12072331
TI  - Is lamivudine with 1-week HBlg as effective as long-term high-dose HBlg in HBV
      prophylaxis after liver transplantation?

PMID- 12072332
TI  - Mediterranean spotted fever in liver transplantation: a case report.

PMID- 12072334
TI  - Donor and recipient characteristics that influence functional capacity of heart
      transplant recipients.

PMID- 12072333
TI  - Comparative effects of Celsior and a new cardioplegic solution on function,
      energy metabolism, and intracellular pH during long-term heart preservation.

PMID- 12072336
TI  - Quality-of-life outcome in cardiac transplantation versus coronary artery bypass
      patients.

PMID- 12072335
TI  - Primary immunosuppression with tacrolimus and mycophenolate mofetil versus
      cyclosporine and azathioprine in heart transplant recipients.

PMID- 12072337
TI  - Cytomegalovirus cholecystitis in a heart transplant recipient.

PMID- 12072338
TI  - Pravastatin treatment-associated reduction in plasma homocysteine in heart
      transplanted patients.

PMID- 12072339
TI  - Early and delayed increase in plasma homocysteine levels in heart transplanted
      patients.

PMID- 12072340
TI  - An investigation of the correlation between C-reactive protein, serum amyloid a
      concentration, and cardiac allograft rejection.

PMID- 12072341
TI  - Human papillomavirus 16 in a heart transplant recipient.

PMID- 12072342
TI  - Alternatives to lung transplantation: lung volume reduction surgery and
      continuous intravenous prostacyclin.

PMID- 12072343
TI  - Pulmonary "twinning" transplantation procedure.

PMID- 12072344
TI  - Long-term outcome of whole pancreatico-duodenal transplantation using arterial
      splenomesenteric anastomosis.

PMID- 12072345
TI  - Successful islet transplantation does not prevent the development of neuropathy
      in alloxan-induced diabetic rats.

PMID- 12072346
TI  - Nonmyeloablative bone marrow transplantation based on deletion of host-anti-donor
      alloreactive cells prevents autoimmune insulitis and diabetes in nonobese
      diabetic mice.

PMID- 12072347
TI  - Late graft rejection following allogeneic bone marrow transplantation in aplastic
      anemia.

PMID- 12072348
TI  - Increasing the target number of nucleated cells and administration of r-metHuG
      CSF expedite neutrophil engraftment in allogeneic bone marrow transplantation.

PMID- 12072349
TI  - Donor/recipient skin and whole-blood cyclosporin A levels in a swine composite
      tissue allograft model: correlation and relationship to rejection.

PMID- 12072350
TI  - Comparison of different immunologic modalities on rat limb allotransplantation.

PMID- 12072351
TI  - The transplantation law: a chance to overcome the shortage of corneal grafts in
      germany?

PMID- 12072352
TI  - A new inactivation/preservation procedure for ossicle homografts.

PMID- 12072353
TI  - Pretransplant heat loading on pancreatic graft reduces posttransplant ischemia
      reperfusion injury.

PMID- 12072354
TI  - Flavonoids exert diverse inhibitory effects on the activation of NF-kappaB.

PMID- 12072355
TI  - High-dose streptozotocin for diabetes induction in adult rhesus monkeys.

PMID- 12072356
TI  - Okadaic acid, an inhibitor of protein phosphatase, exerts a protective effect on
      ischemia-reperfusion injury in rat kidneys.

PMID- 12072357
TI  - Graft immunomodulation by donor irradiation and recipient-specific bone marrow
      cells in rat small bowel transplantation.

PMID- 12072358
TI  - CD83 on dendritic cells: more than just a marker for maturation.
AB  - CD83 has been known for a long time to be one of the best markers for mature
      dendritic cells (DCs). Studies with herpes simplex virus type 1 (HSV-1)-infected
      DCs, whereby the viral infection leads to the degradation of CD83, as well as
      investigations inhibiting CD83 mRNA transport, have provided evidence that CD83
      might also be important for DC biology. Recently, we have shown that the soluble
      extracellular CD83 domain inhibits DC-mediated T-cell proliferation, representing
      the first report describing a functional role for CD83.

PMID- 12072359
TI  - Lymphocyte trafficking, survival and proliferation.

PMID- 12072360
TI  - The expanding world of autoimmunity.

PMID- 12072365
TI  - Antimicrobial peptides are signaling molecules.

PMID- 12072367
TI  - Mammalian defensins in immunity: more than just microbicidal.
AB  - Mammalian defensins are small, cationic, antimicrobial peptides encoded by the
      host that are considered to be important antibiotic-like effectors of innate
      immunity. By using chemokine receptors on dendritic cells and T cells, defensins
      might also contribute to the regulation of host adaptive immunity against
      microbial invasion. Defensins have considerable immunological adjuvant activity
      and linkage of beta-defensins or selected chemokines to an idiotypic lymphoma
      antigen has yielded potent antitumor vaccines. The functional overlap between
      defensins and chemokines is reinforced by reports that some chemokines have
      antimicrobial activities. Although showing similarity in activity and overall
      tertiary structure, the evolutionary relationship between defensins and
      chemokines remains to be determined.

PMID- 12072366
TI  - CD200 and membrane protein interactions in the control of myeloid cells.
AB  - OX2 (now designated CD200) is a membrane protein expressed by a broad range of
      cell types. It is the ligand for a receptor restricted to myeloid cells, with the
      potential to deliver inhibitory signals. This is indicated by the CD200-deficient
      mouse model, in which myeloid cells are more activated when stimulated
      immunologically than cells from normal mice. The unusual tissue distribution of
      CD200 indicates where myeloid cells can be restrictively controlled through cell
      cell contact. Recent data on CD200 will be reviewed in the context of other
      proteins that might have similar roles, in particular, the interaction between
      CD47 and SIRPalpha (CD172a).

PMID- 12072368
TI  - Toll-like receptor signal transduction and the tailoring of innate immunity: a
      role for Mal?
AB  - Recent evidence suggests that there may be specificities in the signal
      transduction pathways activated by different Toll-like receptors (TLRs), with
      different sets of genes being induced by TLR-4 when compared with TLR-2. These
      differences may be because of different signalling adapters, with MyD88 being
      used by several TLRs, and the adapter MyD88-adapter-like (Mal) being recruited
      specifically by TLR-4. The set of genes being induced may be tailored for the
      subsequent elimination of the pathogen being recognized, as a result of
      differences in signal transduction pathways activated by TLRs. These findings may
      ultimately explain how dendritic cells control specific T-cell responses.

PMID- 12072369
TI  - Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster.
AB  - Recognition of bacterial lipopolysaccharide (LPS) by the innate immune system
      elicits strong pro-inflammatory responses that can eventually cause a fatal
      sepsis syndrome in humans. LPS-mediated activation of mammalian cells is believed
      to involve the interaction of LPS with lipopolysaccharide-binding protein (LBP)
      in the serum and, subsequently with CD14. Although there is no doubt that CD14
      binds LPS, CD14 is not capable of initiating a transmembrane activation signal
      because it is a glycosylphosphatidylinositol (GPI)-anchored protein. Accumulating
      evidence has suggested that LPS must interact with a transmembrane receptor(s)
      that is responsible for signal transduction. Integrins CD11c and/or CD18, Toll
      like receptors (TLRs), as well as CD55, have been suggested to serve this
      function. Recently, we have revealed that a signalling complex of receptors is
      formed following LPS stimulation, which comprises heat-shock proteins (Hsps) 70
      and 90, chemokine receptor 4 (CXCR4) and growth differentiation factor 5 (GDF5).
      Taking into account the discovery of the TLRs and the LPS-activation cluster, we
      propose a new model of LPS recognition.

PMID- 12072370
TI  - Intrathymic T-cell migration: a combinatorial interplay of extracellular matrix
      and chemokines?
AB  - Cell migration is crucial for intrathymic T-cell differentiation. Chemokines and
      extracellular matrix proteins per se induce thymocyte migration, and recent data
      suggest a combinatorial role for these molecules in this event. For example,
      thymocyte migration induced by fibronectin plus CXCL12/SDF1-alpha (stromal cell
      derived factor1-alpha) is higher than that elicited by the chemokine alone. If
      such interactions are relevant in the thymus, abnormal expression of any of these
      ligands and/or their corresponding receptors will lead to defects in thymocyte
      migration. At least in the murine model of Chagas disease, this seems to be the
      case. Therefore a better knowledge of this complex biological circuitry will
      provide new clues for understanding thymus physiology and designing therapeutic
      strategies targeting developing T cells.

PMID- 12072371
TI  - Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory
      response?
AB  - Recent evidence has implicated galectins and their ligands as master regulators
      of immune cell homeostasis. Whereas some members of this family, such as galectin
      3, behave as amplifiers of the inflammatory cascade, others, such as galectin-1,
      trigger homeostatic signals to shut off T-cell effector functions. These
      carbohydrate-binding proteins, identified by shared consensus amino acid
      sequences and affinity for beta-galactoside-containing sugars, participate in the
      homeostasis of the inflammatory response, either by regulating cell survival and
      signaling, influencing cell growth and chemotaxis, interfering with cytokine
      secretion, mediating cell-cell and cell-matrix interactions or influencing tumor
      progression and metastasis. The current wealth of new information promises a
      future scenario in which individual members of the galectin family or their
      ligands will be used as powerful anti-inflammatory mediators and selective
      modulators of the immune response.

PMID- 12072374
TI  - Minireview: nuclear receptor coactivators--an update.
AB  - Nuclear receptors (NRs) regulate the expression of target genes in response to
      activation by steroid hormones and other ligands, as well as a variety of other
      signaling pathways. NR coactivators are defined as cellular factors recruited by
      activated NRs that complement their function as mediators of the cellular
      response to endocrine signals. In this review, we will focus upon advances in our
      understanding of the function of coactivators as their characterization has
      progressed from mechanistic studies to an exploration of their biological roles
      in living animals.

PMID- 12072375
TI  - Twists in the tail-change-of-function mutations in thyroid hormone receptors.

PMID- 12072376
TI  - Targeted disruption of the melanin-concentrating hormone receptor-1 results in
      hyperphagia and resistance to diet-induced obesity.
AB  - The hypothalamic neuropeptide melanin-concentrating hormone (MCH) has been
      implicated in a variety of physiological functions including the regulation of
      feeding and energy homeostasis. Two MCH receptors (MCHR1 and MCHR2) have been
      identified so far. To decipher the functional role of the MCH receptors, we have
      generated and phenotypically characterized mice rendered deficient in MCHR1
      expression by homologous recombination. Inactivation of MCHR1 results in mice
      (MCHR1-/-) that are resistant to diet-induced obesity. With a high-fat diet, body
      fat mass is significantly lower in both male (4.7 +/- 0.6 g vs. 9.6 +/- 1.2 g)
      and female (3.9 +/- 0.2 vs. 5.8 +/- 0.5 g) MCHR1-/- mice than that of the wild
      type control (P < 0.01), but the lean mass remains constant. When normalized to
      body weight, female mice are hyperphagic, and male mice are hyperphagic and
      hypermetabolic, compared with wild-type mice. Consistent with the lower fat mass,
      both leptin and insulin levels are significantly lower in male MCHR1-/- mice than
      in the wild-type controls. Our data firmly establish MCHR1 as a mediator of MCH
      effects on energy homeostasis and suggest that inactivation of MCHR1 alone is
      capable to counterbalance obesity induced by a high-fat diet.

PMID- 12072377
TI  - Down-regulation of aortic carboxypeptidase-like protein during the early phase of
      3T3-L1 adipogenesis.
AB  - Aortic carboxypeptidase-like protein (ACLP) is a 175-kDa protein that is
      expressed in vascular smooth muscle cells and contains a signal peptide sequence,
      a lysine- and proline-rich repeating motif, a discoidin-like domain with 35%
      identity to discoidin I, and a carboxypeptidase-like domain that is 39% identical
      with carboxypeptidase E. It is secreted into the extracellular matrix and may
      play a role in abdominal wall development and dermal wound healing. ACLP is also
      expressed in adipose tissue, but at lower levels. In this study we demonstrate
      that ACLP protein and mRNA are severely down-regulated in the early phase of 3T3
      L1 preadipocyte differentiation induced by insulin, dexamethasone, and
      isobutylmethylxanthine. Neither dexamethasone, isobutylmethylxanthine, nor
      insulin treatment alone reduced the level of ACLP protein, suggesting that ACLP
      down-regulation is a differentiation-associated event. ACLP down-regulation
      coincided with the onset of the postconfluent mitotic clonal expansion phase of
      adipogenesis. In contrast, subconfluent 3T3-L1 cell proliferation did not alter
      ACLP expression, suggesting a specific linkage between ACLP and differentiation
      induced clonal expansion. Stable overexpression of ACLP had no effect on
      preadipocyte differentiation assessed by triacylglycerol accumulation and
      peroxisome proliferator-activated receptor-gamma levels. The role of ACLP and its
      marked reduction during adipogenesis merit further study.

PMID- 12072378
TI  - Increased hepatic peroxisome proliferator-activated receptor-gamma coactivator-1
      gene expression in a rat model of intrauterine growth retardation and subsequent
      insulin resistance.
AB  - Uteroplacental insufficiency and subsequent intrauterine growth retardation
      (IUGR) increase the risk of type 2 diabetes in humans and rats. Unsuppressed
      endogenous hepatic glucose production is a common component of the insulin
      resistance associated with type 2 diabetes. Peroxisome proliferator-activated
      receptor-gamma coactivator-1 (PGC-1) mediates hepatic glucose production by
      controlling mRNA levels of glucose-6-phosphatase (G-6-Pase), phosphoenolpyruvate
      carboxykinase (PEPCK), and fructose-1,6-bisphosphatase (FBPase). We therefore
      hypothesized that gene expression of PGC-1 would be increased in juvenile IUGR
      rat livers, and this increase would directly correlate with hepatic mRNA levels
      of PEPCK, G-6-Pase, and FBPase, but not glucokinase. We found that IUGR hepatic
      PGC-1 protein levels were increased to 230 +/- 32% and 310 +/- 47% of control
      values at d 0 and d 21 of life, respectively. Similarly, IUGR hepatic PGC-1 mRNA
      levels were significantly elevated at both ages. Concurrent with the increased
      PGC-1 gene expression, IUGR hepatic mRNA levels of G-6-Pase, PEPCK, and FBPase
      were also significantly increased, whereas glucokinase mRNA levels were
      significantly decreased. These data suggest that increased PGC-1 expression and
      subsequent hepatic glucose production contribute to the insulin resistance
      observed in the IUGR juvenile rat.

PMID- 12072379
TI  - Human beta cells are exceedingly resistant to streptozotocin in vivo.
AB  - Streptozotocin (STZ) causes beta cell death in rodents via the mechanism of DNA
      damage precipitating poly(ADP-ribose) synthetase activation followed by lethal
      nicotinamide adenine dinucleotide depletion. It is unclear whether humans are
      susceptible to this mechanism. Islets were isolated from STZ-sensitive (CD1 mice
      and Lewis rats) and resistant [fish (tilapia)] species and from man and then were
      transplanted into diabetic nude mice under the kidney capsule. Normoglycemic
      recipients with normal glucose tolerance tests on d 30 were injected with
      increasing iv doses of STZ and their plasma glucose levels followed for 5 d;
      glucose tolerance tests were repeated on nondiabetic mice. Mice were then killed;
      grafts and native pancreata were examined. Based upon three criteria (i.e.
      nonfasting plasma glucose levels, glucose tolerance tests, and islet histology),
      the following observations were made: 1) Recipients of rat islets were resistant
      to 25 mg/kg but were uniformly diabetic at doses of 50 or 75 mg/kg. 2) Recipients
      of mouse islets were resistant to 75 mg/kg but were uniformly diabetic at 150 or
      200 mg/kg. 3) Recipients of the fish islets were resistant to 300, 400, and 450
      mg/kg. 4) Recipients of human islets were resistant to 100, 200, 300, 400, and
      450 mg/kg. The results in recipient mice bearing long-term rat, mouse, or fish
      islet grafts were the same as previously published dose-response data for each
      donor species. We extrapolate from our results based on human islet grafts in
      mice that human beta cells are exceedingly resistant to STZ.

PMID- 12072380
TI  - Administration of antivascular endothelial growth factor receptor 2 antibody in
      the early follicular phase delays follicular selection and development in the
      rhesus monkey.
AB  - Angiogenic factors, including vascular endothelial growth factor (VEGF), are
      expressed during follicular development. Our objective was to investigate the
      role of VEGF in the early follicular phase to test whether early cyclic follicle
      development and selection are angiogenesis-dependent processes. After
      documentation of two normal ovulatory cycles, female rhesus monkeys (n = 6)
      received five iv injections of anti-VEGF receptor 2 (anti-VEGF-R2) antibody at 3
      d intervals starting on cycle d 2-4. To evaluate nonspecific effects of the
      treatment antibody, all monkeys also received iv injections of nonspecific
      humanized mouse IgG, using an identical regimen. Daily measurements of FSH, LH,
      estradiol, and progesterone were obtained, throughout the entire period, to
      monitor cyclicity. Administration of anti-VEGF-R2 antibody resulted in a
      significant decline in mean inhibin B levels [control, 181.0 +/- 29.6 (mean +/-
      SE); treatment d 2, 44.5 +/- 13.1 pg/ml; P < 0.05]. No decrease was observed
      after IgG treatment. Anti-VEGF-R2 antibody treatment also delayed the first
      significant increase in estradiol and lengthened the follicular phase from 10-12
      d in the preceding two control cycles to 20-42 d in treatment cycles. FSH and LH
      concentrations increased significantly, within 24 h after anti-VEGF-R2 antibody
      treatment, to levels 2-2.5 times over controls. Our results demonstrate that anti
      VEGF-R2 antibody therapy in the early follicular phase interferes with the normal
      development of the cohort of recruited antral follicles. The data clearly
      indicate that the recruitment-selection process of follicles in the early
      follicular phase in the nonhuman primate is controlled by VEGF, through the VEGF
      R2.

PMID- 12072381
TI  - Prenatal LHRH neurons in nasal explant cultures express estrogen receptor beta
      transcript.
AB  - Sex steroids influence LHRH neuronal activity, exerting a negative or positive
      feedback action, depending on the reproductive state of the animal. Recent
      evidence indicates that LHRH neurons possess the estrogen receptor beta (ERbeta)
      subtype postnatally, suggesting that estrogen may act, in part, directly on LHRH
      neurons. In this study, we identified ERbeta transcript in prenatal LHRH neurons
      as a function of age. Single-cell cDNA pools were made from LHRH neurons
      maintained for 7, 14, and 28 d in vitro (div). Screening of the cDNA pools by PCR
      with ERbeta-specific primers revealed ERbeta-positive LHRH neurons at all three
      ages. However, the number of LHRH cells coexpressing ERbeta transcript decreased
      dramatically between 14 (6/10) and 28 div (1/10). None of the LHRH cells were
      positive for ERalpha transcript. These results indicate that developing LHRH
      neurons express the transcript for ERbeta and suggest that continued expression
      of ERbeta is either a characteristic of LHRH neurons that may require cues from
      the central nervous system and/or periphery or predetermined to be maintained in
      a subpopulation of LHRH neurons.

PMID- 12072382
TI  - Antiproliferative effects of 1alpha,25-dihydroxyvitamin D(3) and vitamin D
      analogs on tumor-derived endothelial cells.
AB  - Although there is abundant evidence that 1alpha,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] inhibits the growth of several cancer cell types, inhibition of
      angiogenesis may also play a role in mediating the antitumor effects of 1,25
      (OH)(2)D(3.) We examined the ability of 1,25-(OH)(2)D(3) to inhibit the growth of
      tumor-derived endothelial cells (TDECs) and normal endothelial cells and to
      modulate angiogenic signaling. 1,25-(OH)(2)D(3) inhibited the growth of TDECs
      from two tumor models at nanomolar concentrations, but was less potent against
      normal aortic or yolk sac endothelial cells. The vitamin D analogs Ro-25-6760,
      EB1089, and ILX23-7553 were also potent inhibitors of TDEC proliferation.
      Furthermore, the combination of 1,25-(OH)(2)D(3) and dexamethasone had greater
      activity than either agent alone. 1,25-(OH)(2)D(3) increased vitamin D receptor
      and p27(Kip1) protein levels in TDECs, whereas phospho-ERK1/2 and phospho-Akt
      levels were reduced. These changes were not observed in normal aortic endothelial
      cells. In squamous cell carcinoma and radiation-induced fibrosarcoma-1 cells,
      1,25-(OH)(2)D(3) treatment caused a reduction in the angiogenic signaling
      molecule, angiopoietin-2. In conclusion, 1,25-(OH)(2)D(3) and its analogs
      directly inhibit TDEC proliferation at concentrations comparable to those
      required to inhibit tumor cells. Further, 1,25-(OH)(2)D(3) modulates cell cycle
      and survival signaling in TDECs and affects angiogenic signaling in cancer cells.
      Thus, our work supports the hypothesis that angiogenesis inhibition plays a role
      in the antitumor effects of 1,25-(OH)(2)D(3).

PMID- 12072383
TI  - Sequential treatment with basic fibroblast growth factor and PTH is more
      efficacious than treatment with PTH alone for increasing vertebral bone mass and
      strength in osteopenic ovariectomized rats.
AB  - The study was designed 1) to determine whether treatment with basic fibroblast
      growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone
      for increasing bone mass and strength and improving trabecular microarchitecture
      in osteopenic ovariectomized rats, and 2) to assess whether prior and concurrent
      administration of the antiresorptive agents estrogen and risedronate suppresses
      the bone anabolic response to treatment with bFGF alone and sequential treatment
      with bFGF and PTH. Three-month-old female Sprague Dawley rats were ovariectomized
      (OVX) or sham-operated (sham) and maintained untreated for 1 yr. Baseline sham
      and OVX rats were killed at this time (15 months of age). Groups of rats were
      injected sc with estrogen (10 microg/kg, 4 d/wk), risedronate (5 microg/kg, 2
      d/wk), or vehicle. At the end of the second week of antiresorptive treatment,
      catheters were inserted into the jugular veins of all rats, and vehicle or bFGF
      at a dose of 250 microg/kg was injected daily for 14 d. Three groups of rats were
      killed at the end of bFGF treatment. The remaining rats were continued on their
      respective antiresorptive therapy and injected sc with vehicle or synthetic human
      PTH-(1-34) at a dose of 80 microg/kg, 5 d/wk, for 8 wk. Lumbar vertebrae were
      processed for cancellous bone histomorphometry and biomechanical testing.
      Ovariectomy resulted in a decrease in vertebral bone mass and strength. Treatment
      of OVX rats for 14 d with bFGF markedly increased osteoblast surface, osteoid
      surface, and osteoid volume compared with vehicle treatment of sham and OVX rats.
      Furthermore, osteoid bridges were observed extending between preexisting
      trabeculae in bFGF-treated OVX rats. Prior and concurrent administration of
      estrogen and risedronate did not suppress these bone anabolic effects of bFGF.
      Treatment of OVX rats with PTH alone increased vertebral cancellous bone mass and
      strength to the level of vehicle-treated sham rats. Sequential treatment of OVX
      rats with bFGF and PTH further augmented vertebral bone mass and strength to a
      level above that observed in OVX rats treated with PTH alone. The improvements in
      bone mass and strength were associated with an increase in trabecular thickness
      in OVX rats treated with PTH alone and with an increase in trabecular thickness
      and node to terminus ratio, an index of trabecular connectivity, in OVX rats
      treated sequentially with bFGF and PTH. Cotreatment with estrogen and risedronate
      did not suppress the anabolic response of bone to bFGF and PTH. In fact, a trend
      for an even greater increase in cancellous bone mass and node to terminus ratio
      was observed in OVX rats treated with risedronate, bFGF, and PTH. These findings
      indicate that sequential treatment with bFGF and PTH is more efficacious than
      treatment with PTH alone for increasing bone mass and strength and improving
      trabecular microarchitecture in osteopenic OVX rats.

PMID- 12072384
TI  - Melatonin regulates energy balance and attenuates fever in Siberian hamsters.
AB  - Fever is considered an important host defense response but requires significant
      metabolic energy. During winter many animals must balance immune function with
      competing physiological demands (i.e. thermoregulation) to survive. Winterlike
      patterns of melatonin secretion induce a number of energy-saving adaptations. For
      instance, Siberian hamsters attenuate the duration of fever during simulated
      short winter day lengths, presumably to conserve energy. To determine the
      proximate role of melatonin in mediating this photoperiodic response, hamsters
      housed in long days were injected with saline or melatonin 4 h before lights off
      for either 1 or 6 wk and assessed for fever following injections of bacterial
      lipopolysaccharide. Fever duration was attenuated (32%) only in hamsters that
      decreased body mass, increased cortisol, and exhibited gonadal regression in
      response to 6 wk of melatonin. Because melatonin-treated hamsters lost
      significant body mass, fever was assessed in a second long-day group following ad
      libitum food intake, food restriction, or 24-h food deprivation. Food restriction
      sufficient to reduce body mass by approximately 25%, but not to reduce leptin,
      did not influence fever, and 24-h food deprivation virtually abolished fever. Our
      data suggest that long-term exposure to long-duration melatonin signals is
      required to induce the physiological changes necessary for short-day immune
      responses, perhaps involving interactions with hormones such as cortisol and
      leptin.

PMID- 12072385
TI  - Stress activation of cortex and hippocampus is modulated by sex and stage of
      estrus.
AB  - Sex plays a major role in stress integration and stress-related affective disease
      states. Notably, neurocircuits regulating organismic responses to stress are
      prime targets for central gonadal steroid action. To assess the roles of sex and
      estrous cycle in central stress integration, we analyzed c-fos mRNA expression in
      hypothalamic-pituitary-adrenocortical-related regions of stressed male and
      cycling female (proestrous, estrous, and diestrous) rats. At 60 min after the
      onset of acute restraint stress, all animal groups showed induction of c-fos mRNA
      in the frontal cortex, cingulate cortex, piriform cortex, hippocampus,
      hypothalamic paraventricular nucleus (PVN), medial amygdala, and lateral septum.
      However, the magnitude of c-fos induction in cortical and hippocampal regions was
      substantially lower in proestrous and estrous females compared with males and
      diestrous females. Sex- and estrus cycle-related changes are region specific, as
      no difference in c-fos induction occurred in the hypothalamic PVN, medial
      amygdala, or ventrolateral septum in any group. Furthermore, induction of c-fos
      mRNA in limbic cortexes (but not hippocampus) was positively correlated with
      progesterone and negatively correlated with ACTH levels. Taken together, this
      study indicates that cortical structures are differentially stress activated in
      females depending on the phase of the estrous cycle, perhaps in a progesterone
      dependent fashion.

PMID- 12072386
TI  - A proinsulin gene splice variant with increased translation efficiency is
      expressed in human pancreatic islets.
AB  - As glucose-induced insulin expression is mainly regulated at the translational
      level, and such regulation often involves the 5'-untranslated region (5'UTR), we
      examined the human proinsulin gene 5'UTR. RT-PCR and sequencing demonstrated that
      a proinsulin splice variant (SPV) generated from a cryptic 5'-splice site and
      retaining the first 26 bp of intron 1 was present in human pancreatic islets from
      normal donors. The expression of this SPV was metabolically regulated, as shown
      by quantitative real-time RT-PCR, revealing a more than 10-fold increase in the
      SPV in isolated human islets incubated at 16.7 mM compared with 1.67 mM glucose.
      In vitro wheat-germ translation and in vivom transfection studies demonstrated
      that the altered 5'UTR of the SPV increased translation. The SPV yielded 4-fold
      more in vitro translated preproinsulin protein than the native proinsulin mRNA,
      and the SPV 5'UTR inserted upstream from a luciferase reporter gene resulted in a
      more than 6-fold higher luciferase activity, suggesting enhanced translation in
      vivo. Retention of the 26 bp changed the proposed secondary RNA structure of the
      SPV, which may facilitate ribosomal binding and explain the increase in
      translation efficiency. These results suggest a novel mechanism by which
      metabolic changes can modulate the expression of 5'UTR SPVs and thereby regulate
      translation efficiency.

PMID- 12072387
TI  - A novel liver X receptor agonist establishes species differences in the
      regulation of cholesterol 7alpha-hydroxylase (CYP7a).
AB  - The liver X receptors, LXRalpha and LXRbeta, are members of the nuclear receptor
      superfamily. Originally identified as orphans, both receptor subtypes have since
      been shown to be activated by naturally occurring oxysterols. LXRalpha knockout
      mice fail to regulate cyp7a mRNA levels upon cholesterol feeding, implicating the
      role of this receptor in cholesterol homeostasis. LXR activation also induces the
      expression of the lipid pump involved in cholesterol efflux, the gene encoding
      ATP binding cassette protein A1 (ABCA1). Therefore, LXR is believed to be a
      sensor of cholesterol levels and a potential therapeutic target for
      atherosclerosis. Here we describe a synthetic molecule named F(3)MethylAA [3
      chloro-4-(3-(7-propyl-3-trifluoromethyl-6-(4,5)-isoxazolyl)propylthio)-phenyl
      acetic acid] that is more potent than 22(R)-hydroxycholesterol in LXR in vitro
      assays. F(3)MethylAA is capable not only of inducing ABCA1 mRNA levels, but also
      increasing cholesterol efflux from THP-1 macrophages. In rat hepatocytes,
      F(3)MethylAA induced cyp7a mRNA, confirming conclusions from the knockout mouse
      studies. Furthermore, in rat in vivo studies, F(3)MethylAA induced liver cyp7a
      mRNA and enzyme activity. A critical species difference is also reported in that
      neither F(3)MethylAA nor 22(R)-hydroxycholesterol induced cyp7a in human primary
      hepatocytes. However, other LXR target genes, ABCA1, ABCG1, and SREBP1, were
      regulated.

PMID- 12072388
TI  - Estrogen receptor alpha inhibits IL-1beta induction of gene expression in the
      mouse liver.
AB  - Estrogens have been suggested to modulate several inflammatory processes. Here,
      we show that IL-1beta treatment induced the expression of approximately 75 genes
      in the liver of ovariectomized mice. 17alpha-Ethinyl estradiol (EE) pretreatment
      reduced the IL-1beta induction of approximately one third of these genes.
      Estrogen receptor alpha (ERalpha) was required for this inhibitory activity,
      because EE inhibition of IL-1beta-stimulated gene expression occurred in ERbeta
      knockout mice, but not in ERalpha knockout mice. EE treatment induced expression
      of 40 genes, including the transcriptional repressor short heterodimer partner
      and prostaglandin D synthase, known modulators of nuclear factor-kappaB
      signaling. However, the ER agonists genistein and raloxifene both inhibited IL
      1beta gene induction without stimulating the expression of prostaglandin D
      synthase, short heterodimer partner, or other ER-inducible genes, indicating that
      induction of gene expression was not required for ER inhibition of IL-1beta
      signaling. Finally, the ability of EE to repress IL-1beta gene induction varied
      among tissues. For example, EE inhibited IL-1beta induction of lipopolysaccharide
      induced c-x-c chemokine (LIX) in the liver, but not in the spleen or lung. The
      degree of EE repression did not correlate with ER expression. cAMP response
      element binding protein-binding protein (CBP)/p300 levels also varied between
      tissues. Together, these results are consistent with a model of in vivo ER
      interference with IL-1beta signaling through a coactivator-based mechanism.

PMID- 12072389
TI  - Effect of peroxisome proliferators on Leydig cell peripheral-type benzodiazepine
      receptor gene expression, hormone-stimulated cholesterol transport, and
      steroidogenesis: role of the peroxisome proliferator-activator receptor alpha.
AB  - In this study, we hypothesized that many of the reported effects of phthalate
      esters and other peroxisome proliferators (PPs) in the testis are mediated by
      members of the PP- activated receptor (PPAR) family of transcription factors
      through alterations in proteins involved in steroidogenesis. Exposure of Leydig
      cells to PPs prevented cholesterol transport into the mitochondria after hormonal
      stimulation and inhibited steroid synthesis, without altering total cell protein
      synthesis or mitochondrial and DNA integrity. PPs also reduced the levels of the
      cholesterol-binding protein peripheral-type benzodiazepine receptor (PBR) because
      of a direct transcriptional inhibition of PBR gene expression in MA-10 Leydig
      cells. MA-10 cells contain mRNAs for PPARalpha and PPARbeta/delta, but not for
      PPARgamma. In vivo treatment of mice with PPs resulted in the reduction of both
      testis PBR mRNA and circulating testosterone levels, in agreement with the
      proposed role of PBR in steroidogenesis. By contrast, liver PBR mRNA levels were
      increased, in agreement with the proposed role of PBR in cell growth/tumor
      formation in nonsteroidogenic tissues. However, PPs did not inhibit testosterone
      production and testis PBR expression in PPARalpha-null mice. These results
      suggest that the antiandrogenic effect of PPs is mediated by a PPARalpha
      dependent inhibition of Leydig cell PBR gene expression.

PMID- 12072390
TI  - Radiation-induced thyroid carcinogenesis as a function of time and dietary iodine
      supply: an in vivo model of tumorigenesis in the rat.
AB  - It is believed that a combination of environmental factors with mutagens induces
      carcinomas derived from thyroid follicular cells. In this study we tried to
      ascertain whether a single short-term exposure to external radiation is
      sufficient to induce thyroid carcinomas in rats under long-term high or low
      dietary iodine intake. Rats were tested over a period of 110 wk under high
      (approximately 10-fold of normal), normal, and low (approximately 0.1-fold of
      normal) daily iodine intake. Forty-day-old animals were subjected to single
      external radiation of 4 Gy or sham radiation. Thyroid function was tested weekly,
      and thyroid morphology was determined after 15, 35, 55, and 110 wk. Iodine
      deficiency, but not high iodine intake, led to a decrease in T(3) and T(4) plasma
      levels, but to an increase in TSH, which became significant after 9 and 11 wk of
      treatment, respectively. Both high and low iodine treatment significantly
      increased the proliferation rate and induced thyroid adenomas, but no
      malignancies after 55 and 110 wk. Radiation with 4 Gy resulted in a significant
      destruction of the follicular structure. Under high and low iodine intakes (50
      80% of animals), but not under normal iodine supply, thyroid carcinomas were
      observed in irradiated rats. Thus, the increased proliferation rate induced under
      the experimental conditions described in this study is apparently not sufficient
      to cause thyroid carcinomas, but the presence of a mutagen-like radiation is
      required. This model may help to define genetic alterations long before
      histological changes are detectable.

PMID- 12072392
TI  - Thrittene, homologous with somatostatin-28((1-13)), is a novel peptide in
      mammalian gut and circulation.
AB  - Preprosomatostatin is a gene expressed ubiquitously among vertebrates, and at
      least two duplications of this gene have occurred during evolution. Somatostatin
      28 (S-28) and somatostatin-14 (S-14), C-terminal products of prosomatostatin
      (ProS), are differentially expressed in mammalian neurons, D cells, and
      enterocytes. One pathway for the generation of S-14 entails the excision of Arg13
      Lys14 in S-28, leading to equivalent amounts of S-28((1-12)). Using an antiserum
      (F-4), directed to the N-terminal region of S-28 that does not react with S-28((1
      12)), we detected a peptide, in addition to S-28 and ProS, that was present in
      human plasma and in the intestinal tract of rats and monkeys. This F-4 reacting
      peptide was purified from monkey ileum; and its amino acid sequence, molecular
      mass, and chromatographic characteristics conformed to those of S-28((1-13)), a
      peptide not described heretofore. When extracts of the small intestine were
      measured by RIA, there was a discordance in the ratio of peptides reacting with F
      4 and those containing the C terminus of ProS, suggesting sites of synthesis for
      S-28((1-13)) distinct from those for S-14 and S-28. This was supported by
      immunocytochemistry, wherein F-4 reactivity was localized in gastrointestinal
      (GI) endocrine cells and a widespread plexus of neurons within the wall of the
      distal gut while immunoreactivity to C-terminal domains of S-14 and S-28 in these
      neurons was absent. Further, F-4 immunoreactivity persisted in similar GI
      endocrine cells and myenteric neurons in mice with a targeted deletion of the
      preprosomatostatin gene. We believe that these data suggest a novel peptide
      produced in the mammalian gut, homologous with the 13 residues of the proximal
      region of S-28 but not derived from the ProS gene. Pending characterization of
      the gene from which this peptide is derived, its distribution, and function, we
      have designated this peptide as thrittene. Its localization in both GI endocrine
      cells and gut neurons suggests that thrittene may function as both a hormone and
      neurotransmitter.

PMID- 12072391
TI  - Coordinate regulation of prostaglandin metabolism for induction of parturition in
      mice.
AB  - Prostaglandins are essential for the initiation of parturition in mice. The peak
      in uterine prostaglandin F(2)(alpha) levels occurs at d 19.0 of gestation, just
      before the onset of labor. Our studies set out to determine the important
      regulatory step(s) involved in this increase of prostaglandin F(2)(alpha). We
      show that cytosolic phospholipase A(2) mRNA, protein, and activity do not
      significantly vary during mouse gestation. Rather, our studies demonstrate that
      cyclooxygenase-1 mRNA is abruptly induced at d 15.5 of gestation, but
      cyclooxygenase-1 protein levels only gradually increase throughout gestation. In
      contrast, cyclooxygenase-2 protein remains constant during gestation. We find
      that prostaglandin F synthase protein increases significantly during gestation
      reaching peak levels between d 15.5 and d 17.5 of gestation. We also find that
      the level of prostaglandin dehydrogenase, responsible for degradation of
      prostaglandins, decreases during late gestation. Taken together these results
      suggest that the regulation of prostaglandin F(2)(alpha) is a complex process
      involving the coordinate induction of synthetic enzymes along with a decrease in
      degradative enzymes involved in prostaglandin metabolism.

PMID- 12072393
TI  - GH and epidermal growth factor signaling in normal and Laron syndrome
      fibroblasts.
AB  - We have investigated and compared GH and epidermal growth factor (EGF) signaling
      in primary human skin fibroblasts from normal subjects and subjects with GH
      binding protein-positive Laron syndrome (LS). In normal human fibroblasts, GH and
      EGF activate the tyrosine phosphorylation of signal transducer and activator of
      transcription (STAT)1 and STAT5b; in LS fibroblasts, EGF does, but GH does not.
      GH also activates the tyrosine phosphorylation of Janus kinase (JAK)2 in normal,
      but not LS, fibroblasts. Similarly, both GH and EGF activate MAPK in normal
      fibroblasts, but only EGF does in the LS fibroblasts. As in the 3T3-F442A mouse
      preadipocyte cell line, GH signaling to mitogen-activated protein kinase is
      partially inhibited by wortmannin treatment, indicating a role for
      phosphatidylinositol 3-kinase (PI3K) in this signaling pathway. The exogenous
      expression of the GH receptor in one family of LS fibroblasts (H1) but not the
      other (M) restores signaling to a STAT5 reporter element. Together, these results
      indicate that the mechanism of defective GH signaling in two families of LS
      fibroblasts are different but that both occur at a level close to, and specific
      for, the GH receptor.

PMID- 12072394
TI  - Temporal requirements of thyroid hormones for seasonal changes in LH secretion.
AB  - The transition between breeding and anestrous seasons in ewes is driven by an
      endogenous rhythm in responsiveness to estradiol negative feedback. One stage of
      this rhythm, the transition to anestrus, requires the presence of thyroid hormone
      during a window of responsiveness that opens in the late breeding season. The
      primary goal of this study was to assess when ewes lose responsiveness to thyroid
      hormone (i.e. when the window closes). In addition, we investigated whether
      thyroid hormone influences aspects of seasonality other than the transition to
      anestrus. Ovariectomized ewes maintained in a simulated natural photoperiod were
      implanted with estradiol, thyroidectomized, and treated with T(4) for 100 d
      beginning at progressively later dates during the anestrous season. Onset of
      neuroendocrine anestrus (decrease in LH), latency to anestrus, and time of onset
      of the subsequent neuroendocrine breeding season (rise in LH) were determined.
      Ewes gradually lost responsiveness to T(4) during the latter half of the
      anestrous season, as judged by increasing latency to the decrease in LH and,
      eventually, failure to exhibit a decrease in LH. Progressively later T(4)
      replacements also caused progressive delays in the subsequent breeding season. In
      contrast, the annual PRL cycle was not significantly affected by thyroidectomy or
      T(4) replacement. These findings indicate that 1) responsiveness to T(4) is lost
      gradually during the mid to late anestrous season; 2) thyroid hormones can
      influence the timing of the breeding season and thus may be required for the
      maintenance or entrainment of the endogenous reproductive rhythm; 3) thyroid
      hormones are not required for all seasonal neuroendocrine cycles.

PMID- 12072396
TI  - Cross-talk between bone morphogenic proteins and estrogen receptor signaling.
AB  - Bone morphogenic proteins (BMPs) play central roles in differentiation,
      development, and physiological tissue remodeling. Estrogens have key roles in a
      variety of biological events, such as the development and maintenance of numerous
      target tissues. Previous studies demonstrated that estrogens suppress BMP
      functions by repressing BMP gene expression. Here we present a novel mechanism
      for the inhibitory effect of estrogens on BMP function. BMP-2-induced activation
      of Sma and Mad (mothers against decapentaplegic)-related protein (Smad) activity
      and BMP-2-mediated gene expression were suppressed by 17beta-E2 in breast cancer
      cells and mesangial cells. E2-mediated inhibition of Smad activation was reversed
      by tamoxifen, an ER antagonist. We provide evidence that the inhibitory action of
      ER on Smad activity was due to direct physical interactions between Smads and ER,
      which represents a novel mechanism for the cross-talk between BMP and ER
      signaling pathways.

PMID- 12072395
TI  - Identification of an upstream pituitary-active promoter of human somatostatin
      receptor subtype 5.
AB  - Somatostatin receptor subtype 5 (sst5) has been linked to inhibition of PRL and
      insulin secretion. We characterized the genomic structure of the human sst5. The
      transcription start site was located 94 nucleotides upstream of the initiator ATG
      codon. Sequence analysis of 5'-inverse PCR products revealed the presence of a
      6.1-kb intron in the 5'-untranslated region. RT-PCR analysis indicated tissue
      specific activation of the newly identified upstream promoter in pituitary, but
      not in small intestine, lung, or placenta. A -1741 promoter directed significant
      levels of luciferase expression in GH(4) rat pituitary cells, Skut-1B endometrium
      cells, and JEG3 chorion carcinoma cells, which was absent in COS-7 monkey kidney
      cells. A minimal -101 promoter was sufficient to allow tissue-specific
      expression. Its activity in COS-7 cells was not enhanced by cotransfection of the
      pituitary-specific transcription factor Pit-1. Analysis of deletion constructs
      revealed a GC-rich region immediately upstream of the transcription start site,
      which is necessary for promoter activity. Somatostatin led to a significant
      inhibition, and forskolin and thyroid hormone to a significant stimulation of
      pituitary-specific promoter activity. Further mapping suggested a cAMP-responsive
      element located between -101 and the transcription start site, and thyroid
      hormone-responsive elements between -1741 and -1269 and between -317 and -101.
      These studies identified an upstream promoter of the sst5 gene with tissue
      specific activity.

PMID- 12072397
TI  - Administration of 5alpha-androstane-3alpha,17beta-diol to female tammar wallaby
      pouch young causes development of a mature prostate and male urethra.
AB  - Secretion of 5alpha-androstane-3alpha,17beta-diol (5alpha-adiol) by the testes of
      the tammar wallaby is responsible for initiation of prostatic development after d
      20 in male pouch young. To ascertain the role of this hormone in the subsequent
      growth and differentiation of the prostate and in the development of the male
      phallus, 5alpha-adiol was administered to tammar female pouch young in two
      regimens. Administration of the hormone by mouth (8 microg/g body weight.wk)
      between d 70 and 150 of pouch life caused prostate development equivalent to that
      in d 150 males and promoted growth and differentiation of the penis, but not
      masculinization of the urethra. Treatment with a small dose of 5alpha-adiol
      enanthate (1 microg/g body weight.wk) from d 20-150 produced similar results.
      However, administration of larger doses of 5alpha-adiol enanthate (10 or 100
      microg/g body weight.wk) from d 20-150 caused supraphysiological growth of the
      prostate, development of a male-type urethra, and penile growth. These results
      indicate that prostatic development and penile growth can be initiated over a
      wide time period, but that formation of a male urethra requires androgen action
      before d 70, when male penile differentiation begins. This further strengthens
      the hypothesis that 5alpha-adiol is the circulating androgen responsible in this
      species for virilization during development.

PMID- 12072398
TI  - Dexamethasone inhibits growth factor-induced type 3 deiodinase activity and mRNA
      expression in a cultured cell line derived from rat neonatal brown fat vascular
      stromal cells.
AB  - Studies examining the regulation of the type 3 deiodinase (D3) have been hampered
      by the lack of cell lines that constitutively express this enzyme. To address
      this issue, a new cell line, designated brown fat vascular-stromal (BVS-1), was
      generated by continuous subculturing of precursor cells derived from the vascular
      stromal fraction of rat neonatal brown fat. BVS-1 cells did not differentiate
      into adipocytes when cultured for 5 d in DMEM supplemented with 2% newborn calf
      serum, 4 nM insulin, 2 nM T(3), and 10 nM dexamethasone (DEX). However, when
      cultured in regular medium, the cells expressed high levels of D3 activity (1-5
      pmol/h per milligram protein) and mRNA. D3 mRNA was markedly induced by treatment
      for 6 h with epidermal growth factor, acid or basic fibroblast growth factors (10
      ng/ml), or a 3-h treatment with a phorbol ester [12-O-tetradecanoylphorbol-13
      acetate (TPA), 1 microM] or 10% fetal bovine serum. However, preincubation of
      cells overnight with 50 nM DEX completely blocked the D3-inducing effects of
      basic fibroblast growth factor. The DEX effect was partially blocked when a
      glucocorticoid receptor antagonist was present. Overnight DEX treatment (50 nM)
      also decreased basal D3 activity by 80%. In summary, we have established BVS-1
      cells as a continuous cell line useful for studying the regulation of D3
      expression. Furthermore, we have shown that DEX inhibits growth factor-induced D3
      expression in these cells.

PMID- 12072399
TI  - The effect of two-day treatment of primary cultured ovine somatotropes with GHRP
      2 on membrane voltage-gated K+ currents.
AB  - Long-term in vivo treatment with synthetic GH-releasing peptides (GHRPs) enhances
      the release of GH induced by endogenous GHRH. The mechanism for such an
      enhancement on GH release is unknown. In this experiment, somatotropes were
      obtained from ovine pituitaries by enzyme dissociation and enriched by density
      centrifugation. Membrane voltage and currents were recorded with whole-cell patch
      clamp configuration. After 48-h treatment with GHRP-2 (10(-8) M), the percentage
      of cells with spontaneous action potential was increased (51 vs. 27%) without
      change of resting potential. This GHRP-2 treatment also increased the amplitude
      of voltage-gated K+ currents (predominantly transient A-type-like current but
      also delayed rectifier or K-type-like current) without modification of
      biophysical kinetics. Down-regulation of protein kinase C (PKC) with phorbol 12
      myristate 13-acetate at the time of adding GHRP-2 blocked the increase in K+
      currents. Inclusion of calphostin C (PKC inhibitor) but not H(89) (protein kinase
      A inhibitor) significantly reduced the increase in K+ currents by GHRP-2.
      Inclusion of actinomycin D (transcription inhibitor) or cycloheximide (protein
      synthesis inhibitor) abolished the increase in K+ currents. These data indicate
      that 48-h GHRP-2 treatment increases the density of K+ channels via PKC and
      channel protein synthesis. Such a modification on K+ channels by GHRP-2 may be
      partially responsible for the change of somatotrope electrophysiological
      properties and sensitivity to GHRH stimulation.

PMID- 12072400
TI  - A targeted thyroid hormone receptor alpha gene dominant-negative mutation (P398H)
      selectively impairs gene expression in differentiated embryonic stem cells.
AB  - Thyroid hormone and retinoic acid (RA) are essential for normal neural
      development in vivo, yet all in vitro differentiation strategies of embryonic
      stem (ES) cells use only RA. We developed a novel differentiation strategy of
      mouse ES cells using T(3). A dominant-negative knock-in point mutation (P398H)
      was introduced into the thyroid hormone receptor alpha gene to determine the
      influence of T(3) on ES cell differentiation. Differentiation promoted by T(3) (1
      nM), RA (1 microM), or combined T(3)/RA was assessed in wild-type (wt) and mutant
      (m) ES cells on the basis of neuronal-specific gene expression and cell cycle.
      T(3) alone stimulated neural differentiation in a similar fashion as that seen
      with RA in both wtES and mES cells. Expression of neurogranin and
      Ca(2+)/calmodulin-dependent kinase IV mRNA (identified in vivo as T(3)-regulated
      genes), however, was markedly reduced in mES, compared with wtES cells. RA
      treatment enhanced apoptosis, significantly greater than that seen with T(3)
      stimulation. T(3) treatment given with RA significantly reduced the apoptotic
      effects of RA, an effect not seen in mES cells. T(3)-induced ES cell neural
      differentiation of thyroid hormone alpha mutant and wtES cells provides an in
      vitro model to study T(3)-dependent gene regulation in neural development. This
      system could also be used to identify novel T(3)-regulated genes. The modulation
      of the apoptotic effects of RA by T(3) may have implications for stem cell
      therapy.

PMID- 12072401
TI  - Role of systemic and local IGF-I in the effects of estrogen on growth and
      epithelial proliferation of mouse uterus.
AB  - IGF-I is a critical regulator of uterine growth, and locally produced uterine IGF
      I could mediate the effects of 17beta-E2 on growth and cellular proliferation. We
      used IGF-I knockout (KO) mice and tissue grafting to determine the roles of local
      and systemic IGF-I in uterine growth and E2 responsiveness. Uteri from adult KO
      mice and neonatal and adult wild-type (WT) mice were grown under the renal
      capsule of female athymic mice for 4 wk. Initial uterine weights of adult KO and
      neonatal WT mice were 5% or less of those of adult WT uteri. Weights of adult WT
      uterine grafts did not increase during grafting. Weights of adult KO and neonatal
      WT uteri exposed to normal systemic levels of IGF-I in athymic hosts increased 20
      to 30-fold to equal or exceed those of adult WT grafts. Uterine epithelial
      height, reduced in KO mice, was restored to WT levels in KO uteri grafted into
      athymic hosts. The absence of local IGF-I production in KO uteri did not impair
      E2- induced epithelial proliferation in KO uterine grafts. Neonatal WT uteri
      grafted into KO hosts showed minimal growth, providing evidence that local
      uterine IGF-I production is insufficient to support uterine growth in the absence
      of systemic IGF-I. E2 treatment of KO females produced minimal uterine growth,
      confirming that lack of IGF-I, rather than E2, caused the uterine hypoplasia. In
      summary, systemic IGF-I supports normal uterine growth and E2 response in the
      absence of local IGF-I. Local IGF-I is not a direct mediator of E2 action in
      uterus, and systemic IGF-I may be more important than previously thought for
      growth of the uterus and other tissues.

PMID- 12072402
TI  - Novel splice variants of type I pituitary adenylate cyclase-activating
      polypeptide receptor in frog exhibit altered adenylate cyclase stimulation and
      differential relative abundance.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts its various
      effects through activation of two types of G protein-coupled receptors, a
      receptor with high affinity for PACAP named PAC1-R and two receptors exhibiting
      similar affinity for both PACAP and vasoactive intestinal polypeptide named VPAC1
      R and VPAC2-R. Here, we report the characterization of PAC1-R and novel splice
      variants in the frog Rana ridibunda. The frog PAC1-R has 78% homology with human
      PAC1-R and is highly expressed in the central nervous system. Two splice variants
      of the frog receptor that display additional amino acid cassettes in the third
      intracellular loop were characterized. PAC1-R25 carries a 25-amino acid insertion
      that matches the hop cassette of the mammalian receptor, whereas PAC1-R41 carries
      a cassette with no homology to any mammalian PAC1-R variant. A third splice
      variant of PAC1-R, exhibiting a completely different intracellular C-terminal
      domain, named PAC1-Rmc has also been identified. Determination of cAMP formation
      in cells transfected with the cloned receptors showed that PACAP activated PAC1
      R, PAC1-R25, and PAC1-R41 with similar potency. In contrast, PACAP failed to
      stimulate adenylate cyclase in cells transfected with PAC1-Rmc. Fusion of PAC1-R
      or PAC1-Rmc with the green fluorescent protein revealed that both receptors are
      expressed and targeted to the plasma membrane in transfected cells. The different
      PAC1-R variants are highly expressed in the frog brain and spinal cord and to a
      lesser extent in peripheral tissues, where only certain isoforms could be
      detected. The present data indicate that in frog, PACAP may act through different
      PAC1-R splice variants that differ in their G(s) protein coupling and their
      abundance in various tissues.

PMID- 12072403
TI  - IGF-binding protein-3-induced growth inhibition and apoptosis do not require cell
      surface binding and nuclear translocation in human breast cancer cells.
AB  - IGF-binding protein-3 (IGFBP-3) has both antiproliferative and proapoptotic
      effects on the growth of human breast cancer cells in vitro. However, the
      mechanisms governing these effects are not well understood. IGFBP-3 has been
      shown to associate with the cell surface through carboxyl-terminal residues. This
      suggests that it may interact with a specific cell surface receptor, although a
      signaling receptor for IGFBP-3 has not yet been fully characterized. IGFBP-3 also
      translocates to the nucleus and has been shown to interact with the nuclear
      RXRalpha, with evidence that this interaction may mediate its growth inhibitory
      and proapoptotic effects. Here we demonstrate that a mutant form of IGFBP-3 that
      has reduced cell surface binding and does not translocate to the nucleus is still
      growth inhibitory, elicits a potent G(1) cell cycle arrest, and induces apoptosis
      via modulation of Bcl-2 family members in human breast cancer cells. This
      suggests the existence of multiple pathways by which IGFBP-3 elicits its growth
      effects.

PMID- 12072404
TI  - Specific detection of type III iodothyronine deiodinase protein in chicken
      cerebellar purkinje cells.
AB  - Because iodothyronine deiodinases play a crucial role in the regulation of the
      available intracellular T(3) concentration, it is important to determine their
      cellular localization. In brain, the presence of type III iodothyronine
      deiodinase (D3) seems to be important to maintain homeostasis of T(3) levels.
      Until now, no cellular localization pattern of the D3 protein was reported in
      chicken brain. In this study polyclonal antisera were produced against specific
      peptides corresponding to the D3 amino acid sequence. Their use in
      immunocytochemistry led to the localization of D3 in the Purkinje cells of the
      chicken cerebellum. Both preimmune serum as well as the primary antiserum
      exhausted with the peptide itself were used as negative controls. Extracts of
      chick cerebellum and liver were made in the presence of Triton X-100 to
      solubilize the membrane-bound deiodinases. Using these extracts in Western blot
      analysis, a band of the expected molecular weight ( approximately 30 kDa) could
      be detected in both tissues. Using a full-length (32)P-labeled type III
      deiodinase cRNA probe, we identified a single mRNA species in the cerebellum that
      was of the exact same size as the hepatic control mRNA (+/-2.4 kb). RT-PCR,
      followed by subcloning and sequence analysis, confirmed the expression of D3 mRNA
      in the chicken cerebellum. In this study we provide the first evidence of the
      presence of the D3 protein in a neuronal cell type, namely Purkinje cells, by
      means of immunocytochemical staining. We were able to detect a protein fragment
      corresponding to the expected molecular mass (30 kDa) for type III deiodinase by
      means of Western blot analysis. RT-PCR as well as Northern blot analysis
      confirmed the presence of D3 mRNA in the cerebellum.

PMID- 12072405
TI  - Mechanism of androgen action on cell proliferation: AS3 protein as a mediator of
      proliferative arrest in the rat prostate.
AB  - Androgens control the proliferation of their target cells first by increasing
      cell proliferation and later by inhibiting the proliferation of those same cells.
      Recently, we reported that the AS3 protein mediates the androgen-induced
      quiescence in androgen-target human cell lines. Our aims were to investigate the
      expression of the AS3 protein in the rat prostate in situ and in human cells in
      culture. Adult rats were separated into four groups (intact, castrated, castrated
      plus 3-d testosterone propionate replacement, and castrated plus 7-d testosterone
      propionate replacement). S9 cells expressing a tetracycline-regulated sense AS3
      were also used. AS3 was expressed in the nuclei of over 90% of the epithelial
      cells and about 40% of the smooth muscle cells of the intact rat prostate. AS3
      was not expressed in castrated rats or during the proliferative phase of androgen
      induced regeneration. It was expressed in intact and castrated animals when the
      prostate has reached adult organ size. The AS3 protein was not expressed in cells
      that incorporate bromodeoxyuridine. These data suggest that AS3 is a mediator of
      the proliferative arrest in the normal rat prostate in situ and human prostate
      cell lines and that its expression is androgen-induced.

PMID- 12072406
TI  - Fibroblast growth factor-9 is an endometrial stromal growth factor.
AB  - Fibroblast growth factor-9 (FGF-9) is an autocrine/paracrine growth factor
      considered to be important for the growth and survival of motorneurons and
      prostate. In this study, we found that FGF-9 was expressed at high levels in
      normal uterine endometrium, especially during the late proliferative phase, which
      is coincident with the rise of estradiol and the time of uterine endometrial
      proliferation. Using quantitative RT-PCR analysis, we found that FGF-9 mRNA was
      expressed primarily by endometrial stromal cells. High affinity receptors of FGF
      9 were detected in both epithelial and stromal cells but with distinct patterns.
      FGFR2IIIc and FGFR3IIIc are abundant in endometrial stromal cell. FGFR2IIIb is
      mostly expressed in endometrial epithelial cells, whereas FGFR3IIIb is found in
      both epithelial and stromal cells. Treatment with FGF-9 induces endometrial
      stromal proliferation in a dose-dependent manner. Expression of FGF-9 in stromal
      cells was induced by 17beta-estradiol but not by progesterone. Furthermore, the
      administration of 17beta-estradiol stimulates endometrial stromal cell
      proliferation and that can be inhibited by cotreatment with anti-FGF-9 antibody.
      Herein we demonstrate, for the first time, that FGF-9 is an autocrine estromedin
      endometrial stromal growth factor that plays roles in cyclic proliferation of
      uterine endometrial stroma.

PMID- 12072407
TI  - Structure, developmental expression, and physiological regulation of zebrafish
      IGF binding protein-1.
AB  - The biological activity and availability of IGFs are regulated by a group of
      secreted proteins that belong to the IGF-binding protein (IGFBP) gene family.
      Although six IGFBPs have been identified and studied in mammals, their
      nonmammalian orthologs remain poorly defined. In this study, we cloned and
      characterized the full-length zebrafish IGFBP-1. Sequence analysis indicated that
      its structure is homologous to mammalian IGFBP-1. Using in situ RNA hybridization
      and RT-PCR, we discovered that IGFBP-1 mRNA was present in all early embryonic
      stages albeit at very low levels. IGFBP-1 mRNA was initially expressed in
      multiple embryonic tissues but became restricted to the liver shortly after
      hatching. In the adult stage, IGFBP-1 mRNA was found only in the liver at low
      levels. Prolonged food deprivation caused a significant increase in the hepatic
      IGFBP-1 mRNA levels, and refeeding restored the IGFBP-1 mRNA to the basal levels.
      When adult fish or embryos were subjected to hypoxic conditions, the IGFBP-1 mRNA
      expression increased dramatically. Intriguingly, the hypoxia-induced IGFBP-1
      expression operated in different embryonic tissues in a developmental-stage
      dependent manner. In early embryos, hypoxia-stimulated IGFBP-1 mRNA expression in
      the pharyngeal arches, ventricle, atrium, and brain. After hatching, the hypoxia
      induced IGFBP-1 expression became liver specific. These results not only provide
      new information about the structural conservation, developmental expression, and
      physiological regulation of the IGFBP-1 gene but also present the opportunity to
      elucidate the developmental role of IGFBP-1 using a unique vertebrate model
      organism.

PMID- 12072409
TI  - Wnt signaling in the ovary: identification and compartmentalized expression of
      wnt-2, wnt-2b, and frizzled-4 mRNAs.
AB  - Ovarian cadherins, in addition to acting as structural (adhesion) molecules, also
      function as modulators of gene activity. The dual role of beta-catenin as an
      intracellular component of the cadherin adhesion complex and as a transcription
      factor provides a possible explanation for these cadherin effects. Because the
      transcriptional activity of beta-catenin is dependent on activation by the wnt
      signaling cascade, we examined whether components of this cascade are expressed
      in the rat ovary. Using RT-PCR with degenerate primers on RNA from ovaries of
      hormone-stimulated immature rats, we identified transcripts for wnt-2 and wnt-2b.
      RT-PCR and in situ hybridization (ISH) demonstrated that granulosa cells express
      wnt-2 mRNA. Because the sequence for rat wnt-2b has not been reported, we
      obtained additional sequence by screening a rat ovarian cDNA library. RT-PCR
      analysis, using primers designed from this wnt-2b cDNA sequence, failed to detect
      transcripts in the ovarian follicular compartment (granulosa and oocyte). ISH
      revealed that the ovarian surface epithelium expresses wnt-2b mRNA. Using a
      similar degenerate RT-PCR approach, we detected expression of a putative wnt
      receptor, frizzled-4 (fzd-4), and a cytoplasmic component of the wnt signaling
      cascade, disheveled-2 (dsh-2), in the rat ovary. Further analyses using both RT
      PCR and ISH indicated that granulosa cells express fzd-4 mRNA. The expression of
      wnt-2b transcripts in rat ovarian surface epithelium prompted us to examine
      whether the homologous gene is expressed in human ovarian cancer cell lines. RT
      PCR, using degenerate and specific primers for wnts, on RNA from five ovarian
      cancer cell lines confirmed the expression of transcripts for wnt-2b. Two
      additional wnt transcripts (wnt-5a and wnt-11) were detected in the cancer cell
      lines and in the rat ovary. These results demonstrate that transcripts
      corresponding to components of the wnt signaling cascade are expressed in the
      immature rat ovary. The localization of these transcripts in specific ovarian
      compartments suggests that this signal transduction pathway may be involved in
      follicular development and ovarian function. Furthermore, because wnts have been
      implicated in the oncogenic transformation of epithelial cells, our results raise
      the possibility that aberrant wnt expression may be involved in ovarian
      tumorigenesis in humans.

PMID- 12072408
TI  - Involvement of inhibitory nuclear factor-kappaB (NFkappaB)-independent NFkappaB
      activation in the gonadotropic regulation of X-linked inhibitor of apoptosis
      expression during ovarian follicular development in vitro.
AB  - Increased X-linked inhibitor of apoptosis (XIAP) expression and suppressed
      follicular apoptosis are important determinants in the regulation of follicular
      development by FSH. The objective of the present study was to examine the role
      and regulation of nuclear factor-kappaB (NFkappaB) in the gonadotropic control of
      granulosa cell XIAP expression and follicular growth in vitro. FSH (100 ng/ml)
      increased rat granulosa cell XIAP mRNA abundance and protein content. The
      gonadotropin also induced granulosa cell p65 subunit-containing NFkappaB
      translocation from cytoplasm to nucleus and increased NFkappaB-DNA binding
      activity. Supershift EMSA indicated the FSH-activated NFkappaB contained p65 and
      p50 subunits. Unlike TNFalpha, FSH failed to elicit a significant change in
      granulosa cell phospho- and total-inhibitory NFkappaB (IkappaB) IkappaB contents
      in vitro and dominant-negative IkappaB expression was ineffective in blocking the
      increase in NFkappaB-DNA-binding activity and XIAP protein content induced by the
      gonadotropin. In contrast, SN50 (a cell permeable inhibitory peptide of NFkappaB
      translocation, 50-200 ng/ml) suppressed FSH-stimulated NFkappaB-DNA binding, XIAP
      expression, and follicular growth. FSH also increased granulosa cell phospho-Akt
      contents, a response sensitive to the PI-3K inhibitor LY294002 (10 microM). In
      conclusion, the present studies demonstrate that the FSH-induced XIAP expression
      is mediated through the NFkappaB pathway through activation of
      phosphatidylinositol 3-kinase rather than the classical IkappaB kinase.

PMID- 12072410
TI  - The estrogen-occupied estrogen receptor functions as a negative regulator to
      inhibit cell proliferation induced by insulin/IGF-1: a cell context-specific
      antimitogenic action of estradiol on rat lactotrophs in culture.
AB  - Estrogens stimulate cell proliferation in typical estrogen-responsive tissues
      including the anterior pituitary gland. Here we report that 17-beta estradiol
      (E2) has estrogen receptor-mediated mitogenic and antimitogenic actions on rat
      lactotrophs in primary culture, depending on the cell context. E2 did not affect
      basal proliferation at 2 d after treatment, but it increased it at 4 d. Insulin
      markedly increased proliferative activity, which was inhibited by simultaneous
      treatment with E2, even after only 2 d of treatment. This antimitogenic action on
      insulin-induced proliferation was also observed with other estrogens but not with
      nonestrogenic steroids. Treatment with antiestrogens in combination with E2
      antagonized both the mitogenic and antimitogenic actions of E2. Antiestrogen
      treatment alone inhibited basal proliferation, and it mimicked the inhibitory
      action of E2 on insulin-induced proliferation with less potency. In parallel with
      cell proliferation, an insulin-induced increase in the cell number of cyclin D1
      immunoreactive lactotrophs was inhibited by E2 treatment. Although the
      antimitogenic action of E2 was seen with a wide range of doses of insulin or IGF
      1, proliferation was stimulated rather than inhibited by E2 when cells were
      treated with serum or forskolin/isobutylmethylxanthine instead of insulin,
      indicating a mitogen-specific, but not proliferative activity-dependent,
      inhibition by E2. The results of estrogen-occupied estrogen receptors as negative
      regulators of proliferation suggest a novel interaction between estrogen and
      growth factors in the regulation of proliferation in estrogen-responsive cells.

PMID- 12072411
TI  - Chronic V2 vasopressin receptor stimulation increases basal blood pressure and
      exacerbates deoxycorticosterone acetate-salt hypertension.
AB  - The present study was intended to determine whether the long-term V2 receptor
      mediated effects of vasopressin on sodium reabsorption in the renal collecting
      duct is an aggravating factor in salt-sensitive hypertension. Deoxycorticosterone
      acetate (DOCA)-salt hypertension was induced in uninephrectomized rats that had
      been chronically pretreated with a V2 agonist (dDAVP; 1-deamino-8D-arginine
      vasopressin; 0.6 microg/kg.d) or a V2 antagonist (SR121463, 3 mg/kg.d) or were
      untreated. Plasma osmolality and natremia were not significantly different in the
      groups. Blood pressure was significantly increased by dDAVP pretreatment (+11 mm
      Hg; P = 0.006), and this effect was exacerbated after DOCA-salt-induced
      hypertension (+17 mm Hg; P = 0.042). The dDAVP-treated rats had a lower
      hematocrit (40 +/- 2% vs. 47 +/- 1% and 45 +/- 2%) and markedly higher
      albuminuria (91 +/- 9 vs. 17 +/- 8 and 15 +/- 8 mg/d), mortality rate (50% vs. 0%
      and 0%), and cardiac and renal hypertrophy than the control and SR121463 groups.
      Histological renal lesions were worsened by V2 agonism and prevented by V2
      antagonism. Renal mRNA expression of beta- and gamma-subunits of the epithelial
      sodium channel was significantly increased by dDAVP treatment (P < 0.05). These
      findings provide evidence that chronic stimulation of vasopressin V2 receptor
      raises basal blood pressure in rats and exacerbates the development of DOCA-salt
      hypertension, organ damage, and mortality. These effects could be due at least in
      part to the sustained stimulation of sodium reabsorption by epithelial sodium
      channel in the distal part of the nephron, which promotes sodium retention.

PMID- 12072412
TI  - Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in
      hypogonadism and infertility.
AB  - Nitric oxide (NO) has been recognized as a modulator in reproductive functions,
      but it is not clear whether NO is required for fertility. The first line of mice
      deficient in neuronal NO synthase (referred to herein as KN1 mice) reproduce
      normally. However, residual neuronal NO synthase (nNOS) activity is detected in
      KN1 mice due to the expression of beta- and gamma-nNOS splice variants. We
      generated a new line of nNOS knockout mice (KN2) lacking exon 6, which codes for
      the heme-binding domain of nNOS. KN2 mice are viable, but mated homozygotes do
      not produce litters, indicating that either one or both sexes are infertile. Male
      KN2 mice show decreased gonad weights, but sperm counts are normal. KN2 males do
      not display mating behavior, and consequently do not leave vaginal plugs when
      housed with wild-type (WT) females. KN2 females show decreased ovary weight, and
      histology reveals decreased corpus luteum counts. RIAs show that KN2 males have
      decreased plasma FSH, whereas KN2 females have increased levels of plasma LH and
      increased hypothalamic GnRH content. Experimental ovarian transplantation
      suggests that central, rather than ovarian, processes are influenced by nNOS, as
      KN2 ovaries ovulate at near-normal rates under WT hormonal control, whereas WT
      ovaries transplanted into KN2 mice have decreased ovulation rates. We observed
      pyloric stenosis in KN2 mice, but plasma leptin levels are normal, and no ketones
      are found, indicating that hypogonadism is not a result of malnutrition. We
      conclude that nNOS is required for normal central hormonal regulation of
      reproductive function.

PMID- 12072413
TI  - 1alpha,25-dihydroxyvitamin D(3) and 24R,25-dihydroxyvitamin D(3) modulate growth
      plate chondrocyte physiology via protein kinase C-dependent phosphorylation of
      extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase.
AB  - Membrane-mediated increases in protein kinase C (PKC) activity and PKC-dependent
      physiological responses of growth plate chondrocytes to vitamin D metabolites
      depend on the state of endochondral maturation; 1alpha,25-dihydroxyvitamin D(3)
      [1alpha,25-(OH)(2)D(3)] regulates growth zone (GC) cells, whereas 24R,25
      (OH)(2)D(3) regulates resting zone (RC) cells. Different mechanisms, including
      protein kinase A signaling, mediate the effects of 1alpha,25-(OH)(2)D(3) and
      24R,25-(OH)(2)D(3) on PKC, suggesting that different mechanisms may also regulate
      any MAPK involvement in the physiological responses. This study used confluent
      cultures of rat costochondral chondrocytes as a model. 1alpha,25-(OH)(2)D(3)
      stimulated MAPK specific activity in GC in a time- and dose-dependent manner,
      evident within 9 min. 24R,25-(OH)(2)D(3) stimulated MAPK in RC; increases were
      dose dependent, occurred after 9 min, and were greatest at 90 min. In both cells
      the effect was due to ERK1/2 activation (p42 > p44 in GC; p42 = p44 in RC). MAPK
      activation was dependent on PKC, but not protein kinase A. The effect of
      1alpha,25-(OH)(2)D(3) required phospholipase C, and the effect of 24R,25
      (OH)(2)D(3) required phospholipase D. Inhibition of cyclooxygenase activity
      reduced the effect of 1alpha,25-(OH)(2)D(3) on MAPK in GC and enhanced the effect
      of 24R,25-(OH)(2)D(3) in RC. Based on MAPK inhibition with PD98059, ERK1/2 MAPK
      mediated the effect of 24R,25-(OH)(2)D(3) on [(3)H]thymidine incorporation and
      [(35)S]sulfate incorporation by RC, but only partially mediated the effect of
      1alpha,25-(OH)(2)D(3) on GC. ERK1/2 was not involved in the regulation of
      alkaline phosphatase specific activity by either metabolite. This paper supports
      the hypothesis that 1alpha,25-(OH)(2)D(3) regulates the physiology of GC via
      rapid membrane-mediated signaling pathways, and some, but not all, of the
      response to 1alpha,25-(OH)(2)D(3) is via the ERK family of MAPKs. In contrast,
      24R,25-(OH)(2)D(3) exerts its effects on RC via PKC-dependent MAPK. Whereas
      1alpha,25-(OH)(2)D(3) increases MAPK activity via phospholipase C and increased
      prostaglandin production, 24R,25-(OH)(2)D(3) increases MAPK via phospholipase D
      and decreased prostaglandin production. The cell specificity, metabolite
      stereospecificity, and the dependence on PKC argue for the participation of
      membrane receptors for 1alpha,25-(OH)(2)D(3) and 24R,25-(OH)(2)D(3) in the
      regulation of ERK1/2 in the growth plate.

PMID- 12072414
TI  - Cystatin 11: a new member of the cystatin type 2 family.
AB  - Cystatin (CST)11, a novel member of the CST type 2 family of cysteine protease
      inhibitors, was identified in Macaca mulatta epididymis by subtractive
      hybridization cloning. The human CST11 gene on chromosome 20p11.2 is located near
      three other CST genes expressed predominantly in the male reproductive tract. The
      CST11 gene spans three exons, a structure similar to that of other CST family 2
      genes. An exon 2-deleted alternative transcript (CST11Delta2) was also
      identified. CST11 mRNA is expressed only in the epididymis as judged by Northern
      blot hybridization and is androgen regulated. The protein is most abundant in the
      initial segment, but is detected throughout the epididymis and on ejaculated
      human sperm. The calculated tertiary structure of CST11 reveals that the three
      regions corresponding to the protease inhibitory wedge of CST3 are similarly
      juxtaposed in CST11, consistent with protease inhibitor function. Intact and exon
      2-deleted CST11 recombinant proteins were tested for antibacterial activity.
      After a 2-h incubation of Escherichia coli with 50 microg/ml recombinant CST11 or
      CST11Delta2, bacterial colony-forming units were reduced to 30% of control,
      indicating that both forms have antimicrobial activity.

PMID- 12072415
TI  - Prevention of thecal angiogenesis, antral follicular growth, and ovulation in the
      primate by treatment with vascular endothelial growth factor Trap R1R2.
AB  - This study was designed to investigate the effects of inhibition of thecal
      angiogenesis on follicular development in the marmoset monkey (Callithrix
      jacchus). To inhibit vascular endothelial growth factor (VEGF), a soluble
      combined truncated form of the fms-like tyrosine kinase (Flt) and kinase insert
      domain-containing receptor (KDR) receptor fused to IgG (VEGF Trap R1R2) was
      administered for 10 d during the follicular phase of the cycle. Changes in
      angiogenesis and follicular cell proliferation were quantified using
      immunocytochemistry for bromodeoxyuridine to obtain a proliferation index, CD31
      to visualize endothelial cell area, and dual staining to distinguish thecal
      endothelial cell proliferation. The effects of the treatment on follicular
      development were assessed by morphometric analyses by measuring follicle
      diameter, thecal thickness, and a proliferation index for granulosa cells.
      Follicular atresia was detected and quantified using the terminal
      deoxynucleotidyltransferase-UTP nick end labeling method. Effects on gene
      expression of VEGF and its receptors, Flt and KDR, were studied by in situ
      hybridization. VEGF Trap R1R2 treatment resulted in a significant decrease in
      thecal proliferation and endothelial cell area, demonstrating the suppression of
      thecal angiogenesis. The absence of a normal thecal vasculature was associated
      with a significantly reduced thecal thickness. Antral follicular development was
      severely compromised, as indicated by decreased granulosa cell proliferation,
      decreased follicular diameter, and lack of development of ovulatory follicles.
      Furthermore, the rate of atresia was significantly increased. VEGF expression in
      granulosa and thecal cells increased after treatment, whereas Flt and KDR
      expressions in thecal endothelial cells were markedly decreased. These results
      show that VEGF Trap treatment is associated with the suppression of follicular
      angiogenesis, which results in the inhibition of antral follicular development
      and ovulation.

PMID- 12072416
TI  - A novel TRH-PFTAIRE protein kinase 1 pathway in the cerebellum: subtractive
      hybridization analysis of TRH-deficient mice.
AB  - TRH has been reported to possess several neurophysiological actions in the brain.
      To gain insights into the molecular mechanisms underlying these effects,
      particularly in the cerebellum, we attempted to clone a cDNA that was regulated
      by TRH using TRH knockout mice and subtractive cDNA analysis. Over 100 clones
      obtained by subtractive hybridization analysis between the wild-type and TRH-1
      cerebellum were analyzed. Four clones among them were identical and cdc2-related
      kinase (PFTAIRE protein kinase 1 (PFTK1)) cDNA, which was previously reported to
      be expressed only in the brain and testis. PFTK1 mRNA levels in the euthyroid TRH
      1- cerebellum supplemented with thyroid hormone were significantly decreased
      compared with those in the wild-type. Induction of PFTK1 mRNA by TRH was also
      observed in a time- and dose-dependent manner in human medulloblastoma-derived
      HTB-185 cells that expressed TRH receptor subtype I mRNA. In addition, treatment
      of 8-Br-cGMP significantly increased PFTK1 mRNA levels, and a specific inhibitor
      of cGMP production, ODQ, completely blocked TRH-induced expression of PFTK1 mRNA.
      Furthermore, induction of PFrK1 mRNA by TRH was significantly inhibited by a NOS
      specific inhibitor, L-NAME, but not by a MEK inhibitor, PD98059 or a calcium
      channel inhibitor, nimodipine. These findings demonstrated, for the first time, a
      novel pathway between a neuropeptide and a cell cycle related peptide in the
      brain, and PFTK1 may be a key regulator for TRH action in t he cerebellum through
      t he NO-cGMP pathway.

PMID- 12072417
TI  - Induction of thyroid hormone-degrading deiodinase in cardiac hypertrophy and
      failure.
AB  - The similarities between the changes in cardiac gene expression in pathological
      ventricular hypertrophy and hypothyroidism suggest a role of impaired cardiac
      thyroid hormone (TH) action in the development of contractile dysfunction during
      chronic cardiac pressure overload. Here we studied the possible involvement of
      altered cardiac TH metabolism using a rat model of right-ventricular (RV)
      hypertrophy induced by pressure-overload. Pathological RV hypertrophy was
      indicated by decreased mRNA levels of sarcoplasmic reticulum(SR) Ca2-ATPase type
      2a (SERCA2a) and myosin heavy chain a (MHCalpha), and increased levels of MHCbeta
      mRNA. Enzyme activity of type HI deiodinase (D3), which converts T4 and T3 to the
      inactive compounds rT3 and 3,3'-T2, respectively, was identified in ventricular
      tissue. This activity was stimulated up to five fold in hypertrophic RV, but
      remained unaltered in the non-hypertrophic left ventricle (LV). A low level of
      type Ideiodinase activity was also detected, which decreased significantly in
      both RV and LV. Stimulation of RV D3 activity was significantly higher in those
      animals in which hypertrophy progressed to heart failure, compared to animals
      that developed compensatory hypertrophy. The induction of a cardiac TR-degrading
      deiodinase maybe expected to result in reduced cellular levels of T3 and thereby
      contribute to a local hypothyroid state in the hypertrophic and, particularly, in
      the failing ventricle.

PMID- 12072420
TI  - Cancer screening in patients with cancer.

PMID- 12072421
TI  - Efficacy of intense screening and treatment for synchronous second primary
      cancers in patients with esophageal cancer.
AB  - BACKGROUND: The optimum management of esophageal cancers with synchronous second
      primary cancer (SPC) has not been determined. The aim of this study was to
      evaluate the efficacy of intense screening and treatment for esophageal cancers
      with synchronous SPC. METHODS: Between 1981 and 1997, 1479 patients with
      esophageal cancers were screened for synchronous SPC during the process of
      initial staging. Radical treatment was recommended for esophageal cancer and
      synchronous SPC in cases for whom both cancers were curable. Treatment results
      for esophageal cancer patients with or without synchronous SPC were compared.
      RESULTS: Among 1479 patients, 155 (10.5%) were found to have 166 synchronous SPC.
      Primary sites included the stomach in 65, the head and neck in 44, the
      colon/rectum in 27, the lung in 14 and other sites in 16 patients. Clinical
      stages of synchronous SPC were stage I in 41%, stage II in 20%, stage III in 25%
      and stage IV in 14%. The 5-year overall survival rates by clinical stages of
      esophageal cancers (stage 0, I, II, III, IV) in patients with synchronous SPC
      were 51% (95% CI, 23-78%), 43% (95% CI, 18-68%), 11% (95% CI, 0-22%), 14% (95%
      CI, 0-28%) and 12% (95% CI, 1-22%), respectively. The 5-year overall survival
      rate for patients with or without synchronous SPC were 20% (95% CI, 13-28%) and
      32% (95% CI, 29-35%), respectively. No significant difference was observed
      between both groups (p = 0.2562). CONCLUSIONS: Intense screening and treatment
      may be justifiable in the light of the high detection rate of curable SPC and the
      reasonable survival of patients with synchronous SPC. However, a prospective
      study including cost-benefit analysis is needed to provide the evidence to
      justify the intense screening and treatment.

PMID- 12072422
TI  - A phase I/II study of carboplatin and paclitaxel in patients with epithelial
      ovarian cancer.
AB  - BACKGROUND: This study was conducted to investigate the recommended dose of
      paclitaxel for use in combination with a fixed dose of carboplatin and to
      evaluate the toxicity and efficacy of carboplatin-paclitaxel combination
      chemotherapy in patients with epithelial ovarian cancer. METHODS: One hundred and
      ten patients were enrolled in the Phase I/II study and 97 patients were evaluated
      for further analysis, excluding 13 ineligible patients or patients with
      infringement of protocol: 15 patients for the Phase I and 82 for the Phase II
      study. In the Phase I trial, we studied dose escalation using a carboplatin dose
      of AUC 5 and paclitaxel levels of 150, 175 and 200 mg/m(2). The grades of
      toxicity of the regimen of all patients enrolled in the Phase II study (n = 82),
      the progression-free survival time (PFS) of optimal-debulked patients and
      complete responders (n = 62) and the response rate of suboptimal-debulked
      patients (n = 39) were investigated. RESULTS: After observing grade 4 neutropenia
      in four of six patients in the paclitaxel 200 mg/m(2) administration group, we
      chose 175 mg/m(2) as the recommended dose of paclitaxel in this regimen. At this
      dose, the median of PFS and response rate were 432 days (range, 19-907 days) and
      66.7%, respectively. CONCLUSION: Combination chemotherapy using paclitaxel 175
      mg/m(2) and carboplatin AUC 5 is very well tolerated and highly effective for the
      treatment of ovarian cancer.

PMID- 12072423
TI  - Infusion of a high number of CD34+ cells provides a rapid hematopoietic recovery
      and cost savings in autologous peripheral blood stem cell transplantation.
AB  - BACKGROUND: The objectives of this study were to evaluate the effect of the
      number of infused CD34+ cells on hematopoietic recovery and on the cost in
      autologous peripheral blood stem cell transplantation (PBSCT). METHODS: Sixty
      nine patients who received autologous PBSCT (ABSCT) were divided into three
      groups defined by the number of infused CD34+ cells. The number of days until 0.5
      x 10(9)/l neutrophils and 50 x 10(9)/l platelets, the number of transfused blood
      products, the febrile days, the duration of parenteral antibiotics and the cost
      of additional supportive care (transfusions of blood products and parenteral
      antibiotics) were analyzed. RESULTS: Twenty-three patients received <2.5 x
      10(6)/kg of CD34+ cells (group A), 25 patients received > or = 2.5 to 5 x
      10(6)/kg of CD34+ cells (group B) and 21 patients received > or = 5 x 10(6)/kg of
      CD34+ cells (group C). Patients in group C had rapid neutrophil (p < 0.01) and
      platelet (p < 0.05) recovery and required less platelet transfusions (p < 0.05)
      than patients in other groups. Transfusions of red blood cell concentrates, the
      duration of febrile days or parenteral antibiotics were not statistically
      different between the two groups. The patients in group C required significantly
      lower costs for platelet concentrates and additional supportive care (p < 0.05).
      CONCLUSION: Infusion of > or = 5 x 10(6)/kg of CD34+ cells in ABSCT shortens
      hematopoietic recovery and reduces costs for additional supportive care.

PMID- 12072424
TI  - Prediction of chemotherapy response in untreated malignant lymphomas using
      technetium-99m methoxyisobutylisonitrile scan: comparison with P-glycoprotein
      expression and other prognostic factors. A preliminary peport.
AB  - BACKGROUND: The purpose of this study was to predict chemotherapy response in
      untreated malignant lymphomas using technetium-99m methoxyisobutylisonitrile (Tc
      MIBI) scan. METHODS: Twenty-five patients with malignant lymphoma were studied
      before receiving chemotherapy. Early Tc-MIBI scan was performed 10 min after
      intravenous injection of Tc-MIBI. Immunohistochemical analyses were performed on
      multiple non-consecutive sections of the biopsy specimens to determine Pgp
      expression. Chemotherapy response was evaluated in the first 1-2 years after
      completion of treatment by clinical and radiological methods. RESULTS: The mean
      tumor-to-background ratio of the 15 patients with good response (3.3 +/- 0.6) was
      significantly higher than that of the 10 patients with poor response (1.2 +/-
      0.1). Among the 15 patients with good response to chemotherapy, all had positive
      Tc-MIBI scan results but negative Pgp expression. Among the 10 patients who had
      poor response to chemotherapy, all 10 had negative Tc-MIBI scan, but six patients
      had positive Pgp expression and four had negative Pgp expression. Significant
      differences were found in the incidences of good and poor responses determined by
      Tc-MIBI scan and Pgp expression. However, there were no significant differences
      in the incidences of good and poor responses for other prognostic factors.
      CONCLUSION: Compared with other prognostic factors, early Tc-MIBI scan more
      accurately predicts chemotherapy response in patients with malignant lymphoma.

PMID- 12072425
TI  - Invasive ductal adenocarcinoma of the remnant pancreatic body 9 years after
      resection of an intraductal papillary-mucinous carcinoma of the pancreatic head:
      a case report and comparison of DNA sequence in K-ras gene mutation.
AB  - Recently, there have been a few case reports of invasive ductal adenocarcinoma
      (IDC) developed in the remnant pancreas after partial pancreatectomy for
      intraductal papillary-mucinous neoplasm (IPMN). It is necessary to clarify their
      histogenetic relationships among two sporadic tumors and their surrounding duct
      epithelium and it would be more reliable if genetic analysis is added to the
      conventional histology. We report a 76-year-old woman who received
      pancreaticoduodenectomy for IPMN with a focal in situ carcinoma (IPMC), which was
      transitional to the surrounding duct epithelium with papillary proliferation and
      a wide variety of dysplasia. Nine years after the operation, she died of IDC in
      the remnant pancreatic body and its surrounding duct epithelium consisted of
      hyperplastic mucous cells with slight-mild dysplasia. Analysis of K-ras mutation
      at codon 12 (wild-GGT) by direct sequencing after polymerase chain reaction
      indicated that their transitioning patterns differed from each other: CGT in
      IPMC; no mutation in the mildly dysplastic duct epithelium around IPMC; GAT in
      IDC of the remnant pancreas; and AGT in mucous cell hyperplasia with mild
      dysplasia close to the IDC. This is the first report in which the DNA sequence of
      K-ras mutation was determined for the two sporadic pancreatic cancers and
      surrounding duct changes. The following two suggestions are made: (1) the cell
      origin might have differed between the two types of cancer (IDC and IPMC); and
      (2) no precursor lesion toward IDC or IPMC was identified in their surrounding
      duct epithelium.

PMID- 12072426
TI  - Two cases of advanced renal cell cancer with prolonged survival of 8 and 12
      years.
AB  - The prognosis of Stage IV renal cell cancer (RCC) is poor. Most of the long-term
      survivors are patients with resected solitary metastases. We report two cases of
      inoperable Stage IV RCC with survival of 8 and 12 years. While it is possible
      that the natural history of the disease contributed to such survival, the long
      duration of stable disease was remarkable.

PMID- 12072427
TI  - Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic
      receptor) in the mechanism of CYP3A4 inhibition by xenobiotics.
AB  - Cytochrome P450 monooxygenase 3A4 (CYP3A4) is responsible for the metabolism of
      endogenous steroids and drugs in liver. Many inducers of human CYP3A4, such as
      rifampicin, bind to the orphan nuclear receptor SXR (steroid and xenobiotic
      receptor) as ligands and stimulate transcription on xenobiotic response elements
      located in the CYP3A4 promoter. Conversely, it is not known whether SXR mediates
      the transcriptional repression. We thus examined transcriptional repression of
      SXR and its interaction with corepressors, NCoR (nuclear receptor corepressor)
      and SMRT (silencing mediator for retinoid and thyroid receptors) using reporter
      assays in the absence and presence of ligand. Cotransfection of SMRT, but not
      NCoR, inhibited not only basal but also rifampicin-induced transcriptional
      activity of SXR on the CYP3A4 promoter through specific SMRT-SXR interaction in
      HepG2 cells. Interestingly, rifampicin also increased the interaction of SXR with
      SMRT as well as with coactivator SRC-1. On the other hand, the anti-fungal agent
      ketoconazole decreased SXR interaction with both SRC-1 and SMRT. Ketoconazole
      partially inhibited corticosterone-induced SXR-mediated transcription on the
      CYP3A4 promoter. Taken together, our results suggest that the differential
      interaction of coactivators and corepressors induced by various xenobiotics may
      alter SXR-mediated transcription. Further, the effects of ketoconazole on the
      CYP3A4 gene suppression may explain, in part, drug-induced inhibition of the
      CYP3A4 action at the transcriptional level.

PMID- 12072428
TI  - Linear non-competitive inhibition of solubilized human gamma-secretase by
      pepstatin A methylester, L685458, sulfonamides, and benzodiazepines.
AB  - Cerebral deposition of amyloid beta-protein (A beta) is believed to play a key
      role in the pathogenesis of Alzheimer's disease. Because A beta is produced from
      the processing of amyloid beta-protein precursor (APP) by beta- and gamma
      secretases, these enzymes are considered important therapeutic targets for
      identification of drugs to treat Alzheimer's disease. Unlike beta-secretase,
      which is a monomeric aspartyl protease, gamma-secretase activity resides as part
      of a membrane-bound, high molecular weight, macromolecular complex. Pepstatin and
      L685458 are among several structural classes of gamma-secretase inhibitors
      identified so far. These compounds possess a hydroxyethylene dipeptide isostere
      of aspartyl protease transition state analogs, suggesting gamma-secretase may be
      an aspartyl protease. However, the mechanism of inhibition of gamma-secretase by
      pepstatin and L685458 has not been elucidated. In this study, we report that
      pepstatin A methylester and L685458 unexpectedly displayed linear non-competitive
      inhibition of gamma-secretase. Sulfonamides and benzodiazepines, which do not
      resemble transition state analogs of aspartyl proteases, also displayed potent,
      non-competitive inhibition of gamma-secretase. Models to rationalize how
      transition state analogs inhibit their targets by non-competitive inhibition are
      discussed.

PMID- 12072429
TI  - Characterization of rat NDRG2 (N-Myc downstream regulated gene 2), a novel early
      mineralocorticoid-specific induced gene.
AB  - The early phase of the stimulatory action of aldosterone on sodium reabsorption
      in tight epithelia involves hormone-regulated genes that remain to be identified.
      Using a subtractive hybridization technique on isolated renal cortical collecting
      ducts from rats injected with a physiological dose of aldosterone, we have
      identified an early response cDNA highly homologous to human and murine NDRG2 (N
      Myc downstream regulated gene 2), which consists of four isoforms and belongs to
      a new family of differentiation-related genes. NDRG2 mRNA was expressed in
      classical aldosterone target epithelia, and in the kidney, it was specifically
      located in the collecting duct, the site of aldosterone-regulated sodium
      absorption. NDRG2 mRNA was increased within 45 min by aldosterone in the kidney
      and distal colon, whereas it was unaffected in the heart. In the RCCD2 collecting
      duct cell line, NDRG2 mRNA was enhanced as early as 15 min after aldosterone
      addition by transcription-dependent effects. NDRG2 was induced by aldosterone
      concentrations as low as 10(-9) M, and a maximal effect was observed at 10(-8) M.
      In contrast, the glucocorticoid dexamethasone was ineffective in NDRG2
      expression, whereas the glucocorticoid-regulated gene sgk was induced. Taken
      together, these results indicate that NDRG2 regulation by aldosterone is an early
      mineralocorticoid-specific effect. Interestingly, NDRG2 is homologous to
      Drosophila MESK2, a component of the Ras pathway, suggesting that activation of
      the Ras cascade may play a significant role in mineralocorticoid signaling.

PMID- 12072430
TI  - Blockade of AP1 transactivation abrogates the abnormal expression of breast
      cancer-specific gene 1 in breast cancer cells.
AB  - Breast cancer-specific gene 1 (BCSG1) is not expressed in normal breast tissue
      but is highly expressed in the vast majority of invasive and metastatic breast
      carcinomas. When over-expressed, BCSG1 significantly stimulates the proliferation
      and invasion of breast cancer cells. The accumulated evidence suggests that the
      aberrant expression of BCSG1 in breast carcinomas is caused by transcriptional
      activation of the BCSG1 gene. However, the transcription factors that activate
      BCSG1 transcription have not been identified. In this study, we extensively
      investigated the role of AP1 in BCSG1 expression in breast cancer cells. We
      demonstrate that there are two closely located AP1 binding sites residing in the
      first intron of the BCSG1 gene. Mutation of either AP1 motif on the BCSG1
      promoter constructs markedly reduces the promoter activity. We further show that
      12-O-tetradecanoylphorbol-13-acetate (TPA) increases BCSG1 mRNA expression and up
      regulates BCSG1 promoter activity through the intronic AP1 sites. The effect of
      TPA on BCSG1 transcription is also demonstrated under in vivo conditions in
      intact cells by using chromatin immunoprecipitation assays that show the TPA
      induced binding of c-Jun to the chromatin region encompassing the intronic AP1
      sites. Finally, to examine the direct effect of AP1 transactivation on BCSG1
      expression, we established stable cell lines of T47D that express the dominant
      negative mutant of c-Jun, TAM67. RT-PCR and Western blot analyses demonstrated
      that levels of BCSG1 mRNA and protein in TAM67 transfectants were drastically
      reduced as compared with mock-transfected cells. Furthermore, inhibition of BCSG1
      expression by blocking AP1 transactivation produced a similar repressive effect
      on cell growth as that by expressing BCSG1 antisense mRNA. We show that the
      anchorage-independent growth of T47D cells expressing either TAM67 or BCSG1
      antisense mRNA is significantly inhibited. Taken together, we provide strong
      evidence that AP1 plays an overriding role in the transcription of the BCSG1 gene
      and that blockade of AP1 transactivation down-regulates BCSG1 expression and
      suppresses tumor phenotype.

PMID- 12072431
TI  - Calcium and calpain as key mediators of apoptosis-like death induced by vitamin D
      compounds in breast cancer cells.
AB  - The active form of vitamin D(3) (1,25(OH)(2)D(3)) induces an increase in the
      intracellular free calcium ([Ca(2+)](i)) and caspase-independent cell death in
      human breast cancer cells. Here we show that the treatment of MCF-7 breast cancer
      cells with 1,25(OH)(2)D(3) or its chemotherapeutic analog, EB 1089, releases
      Ca(2+) from the endoplasmic reticulum. The increase in [Ca(2+)](i) was associated
      with the activation of a calcium-dependent cysteine protease, mu-calpain.
      Interestingly, ectopic expression of a calcium-binding protein, calbindin-D(28k),
      in MCF-7 cells not only attenuated the elevation in [Ca(2+)](i) and calpain
      activation, but also reduced death triggered by vitamin D compounds. Similarly,
      the inhibition of calpain activity by structurally unrelated chemical inhibitors
      increased the survival of the cells and reduces the amount of annexin V-positive
      cells. Despite the complete absence of effector caspase activation, transmission
      electron microscopy of MCF-7 cells treated with 1,25(OH)(2)D(3) or EB 1089
      revealed apoptosis-like morphology characterized by the condensed cytoplasm,
      nuclei, and chromatin. Overall, these results suggest that calpain may take over
      the role of the major execution protease in apoptosis-like death induced by
      vitamin D compounds. Thus, these compounds may prove useful in the treatment of
      tumors resistant to therapeutic agents dependent on the classical caspase
      cascade.

PMID- 12072432
TI  - Microsomal triacylglycerol transfer protein is required for lumenal accretion of
      triacylglycerol not associated with ApoB, as well as for ApoB lipidation.
AB  - The assembly of very low density lipoproteins in hepatocytes requires the
      microsomal triacylglycerol transfer protein (MTP). This microsomal lumenal
      protein transfers lipids, particularly triacylglycerols (TG), between membranes
      in vitro and has been proposed to transfer TG to nascent apolipoprotein (apo) B
      in vivo. We examined the role of MTP in the assembly of apoB-containing
      lipoproteins in cultured murine primary hepatocytes using an inhibitor of MTP.
      The MTP inhibitor reduced TG secretion from hepatocytes by 85% and decreased the
      amount of apoB100 in the microsomal lumen, as well as that secreted into the
      medium, by 70 and 90%, respectively, whereas the secretion of apoB48 was only
      slightly decreased and the amount of lumenal apoB48 was unaffected. However,
      apoB48-containing particles formed in the presence of inhibitor were lipid-poor
      compared with those produced in the absence of inhibitor. We also isolated a pool
      of apoB-free TG from the microsomal lumen and showed that inhibition of MTP
      decreased the amount of TG in this pool by approximately 45%. The pool of TG
      associated with apoB was similarly reduced. However, inhibition of MTP did not
      directly block TG transfer from the apoB-independent TG pool to partially
      lipidated apoB in the microsomal lumen. We conclude that MTP is required for TG
      accumulation in the microsomal lumen and as a source of TG for assembly with
      apoB, but normal levels of MTP are not required for transferring the bulk of TG
      to apoB during VLDL assembly in murine hepatocytes.

PMID- 12072433
TI  - Several PATCHED1 missense mutations display activity in patched1-deficient
      fibroblasts.
AB  - Mutations in mouse and human patched1 (ptc1) genes are associated with birth
      defects and cancer. Ptc1 is a receptor for Hedgehog (Hh) signaling proteins. Hh
      proteins activate transcription of target genes, including ptc1, and Ptc1
      represses those genes, both by regulating the activity of Gli transcription
      factors. We have established mammalian cell lines with reduced Ptc1 function and
      a lacZ reporter to investigate Hh signal transduction. Embryonic fibroblasts were
      derived from mice, heterozygous or homozygous for a ptc1 mutation that inserts
      lacZ under the control of the ptc1 promoter (ptc1-lacZ). In heterozygous ptc1
      cells, ptc1-lacZ was expressed at low levels but could be induced by Sonic
      Hedgehog (Shh) and Gli-1. Homozygous ptc1 cells expressed high levels of ptc1
      lacZ without Hh stimulation. ptc1-lacZ expression was dependent on cell density
      in ptc1 homozygotes and Hh-stimulated heterozygotes but was independent of
      density when Gli1 was used to activate ptc1-lacZ. A wild-type ptc1 transgene
      introduced into homozygous ptc1 cells greatly reduced ptc1-lacZ expression.
      Expression of either half of Ptc1 alone resulted in improper maturation of the
      protein and a failure to complement the ptc1(-/-) cells. When co-expressed, both
      Ptc1 halves matured and had an activity similar to that of the intact protein.
      Three missense PTCH1 mutations exhibited significant functions in homozygous ptc1
      cells. The missense mutants retained activity when expressed at about 10-fold
      lower levels and appeared as stable as wild-type Ptc1. These studies suggest that
      some tumors and disease phenotypes may arise from small reductions in PTCH1
      activity.

PMID- 12072434
TI  - Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is
      sumolated in vivo.
AB  - The members of the AP-2 family of transcription factors are developmentally
      regulated and have distinct yet overlapping functions in the regulation of many
      genes governing growth and differentiation. All AP-2 factors appear to be capable
      of binding very similar DNA recognition sites, and the determinants of functional
      specificity remain to be elucidated. AP-2 transcription factors have been shown
      to act both as transcriptional activators and repressors in a promoter-specific
      manner. Although several mediators of their activation function have been
      suggested, few mechanisms for the repression or down-regulation of
      transactivation have been described. In a two-hybrid screen for proteins
      interacting with AP-2 factors, we have identified the UBC9 gene that encodes the
      E2 (ubiquitin carrier protein)-conjugating enzyme for the small ubiquitin-like
      modifier, SUMO. The interaction domain resides in the C-terminal half of AP-2,
      which contains the conserved DNA binding and dimerization domains. We have
      detected sumolated forms of endogenous AP-2 in mammalian cells and have further
      mapped the in vivo sumolation site to conserved lysine 10. Transient transfection
      studies indicate that sumolation of AP-2 decreases its transcription activation
      potential, and we discuss the possible mechanisms for the observed suppression of
      AP-2 transactivation.

PMID- 12072435
TI  - CCAAT/enhancer-binding proteins beta and delta mediate the repression of gene
      transcription of cartilage-derived retinoic acid-sensitive protein induced by
      interleukin-1 beta.
AB  - Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein
      expressed by chondrocytes; the expression is repressed by interleukin 1 beta (IL
      1 beta). To investigate the transcriptional mechanism, by which CD-RAP expression
      is suppressed by IL-1 beta, deletion constructs of the mouse CD-RAP promoter were
      transfected into rat chondrocytes treated with or without IL-1 beta. The results
      revealed an IL-1 beta-responsive element located between -2138 and -2068 bp. As
      this element contains a CAAT/enhancer-binding protein (C/EBP) motif, the function
      of C/EBP beta and C/EBP delta was examined. IL-1 beta stimulated the expression
      of C/EBP beta and -delta, and the direct binding of C/EBP beta to the C/EBP motif
      was confirmed. The -2251-bp CD-RAP promoter activity was down-regulated by co
      transfection with C/EBP expression vectors. Mutation of the C/EBP motif abolished
      the inhibitory response to IL-1 beta. Additionally, C/EBP expression vectors were
      found to down-regulate the construct containing the promoter and enhancer of the
      type II collagen gene. Finally, the enhancer factor, Sox9, was shown to bind
      adjacent to the C/EBP site competing with C/EBP binding. Taken together, these
      results suggest that C/EBP beta and -delta may play an important role in the IL-1
      beta-induced repression of cartilage-specific proteins and that expression of
      matrix proteins will be influenced by the availability of positive and negative
      trans-acting factors.

PMID- 12072436
TI  - A ubiquitin-interacting motif (UIM) is essential for Eps15 and Eps15R
      ubiquitination.
AB  - An important negative control mechanism in the signaling of epidermal growth
      factor (EGF) is the endocytosis and subsequent degradation of activated EGF
      receptors. Eps15 and its related partner Eps15R play a key role in clathrin
      mediated endocytosis of transmembrane receptors. Upon EGF stimulation of the
      cell, Eps15 becomes both phosphorylated on tyrosine residues and
      monoubiquitinated. Although tyrosine phosphorylation of Eps15 has been implicated
      in EGF receptor internalization, the function of Eps15 ubiquitination is not
      known. Using a mutational approach, we have found that the second ubiquitin
      interacting motif (UIM) of Eps15 and Eps15R is essential for their
      ubiquitination. This UIM partially overlaps with the recently characterized
      nuclear export signal in Eps15. We show that these two overlapping motifs have
      different structural requirements with respect to nuclear export signal versus
      ubiquitination signal activity. Our data demonstrate that the UIM does not
      contain the ubiquitin acceptor site but functions as a recruitment site for the
      ubiquitination machinery leading to the monoubiquitination of both Eps15 and
      Eps15R.

PMID- 12072437
TI  - A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure
      and effect on macrophage cytokine production.
AB  - Rhodococcus equi is a major cause of foal morbidity and mortality. We have
      investigated the presence of lipoglycan in this organism as closely related
      bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM)
      that may play multiple roles as virulence determinants. The lipoglycan was
      structurally characterized by gas chromatography-mass spectrometry following
      permethylation, capillary electrophoresis after chemical degradation, and (1)H
      and (31)P and two-dimensional heteronuclear nuclear magnetic resonance studies.
      Key structural features of the lipoglycan are a linear alpha-1,6-mannan with side
      chains containing one 2-linked alpha-d-Manp residue. This polysaccharidic
      backbone is linked to a phosphatidylinositol mannosyl anchor. In contrast to
      mycobacterial LAM, there are no extensive arabinan domains but single terminal
      alpha-d-Araf residue capping the 2-linked alpha-d-Manp. The lipoglycan binds
      concanavalin A and mannose-binding protein consistent with the presence of t
      alpha-d-Manp residues. We studied the ability of the lipoglycans to induce
      cytokines from equine macrophages, in comparison to whole cells of R. equi. These
      data revealed patterns of cytokine mRNA induction that suggest that the
      lipoglycan is involved in much of the early macrophage cytokine response to R.
      equi infection. These studies identify a novel LAM variant that may contribute to
      the pathogenesis of disease caused by R. equi.

PMID- 12072438
TI  - Inhibition of the splicing of glucose-6-phosphate dehydrogenase precursor mRNA by
      polyunsaturated fatty acids.
AB  - Polyunsaturated fatty acids inhibit the expression of hepatic glucose-6-phosphate
      dehydrogenase (G6PD) by changes in the amount of G6PD pre-mRNA in the nucleus in
      the absence of changes in the transcription rate of the gene. We have compared
      the nuclear accumulation of partially and fully spliced mRNA for G6PD in the
      livers of mice fed diets high versus low in polyunsaturated fat. Consumption of a
      diet high in polyunsaturated fat decreased the accumulation of partially spliced
      forms of the G6PD pre-mRNA. Examining the fate of multiple introns within the
      G6PD primary transcript indicated that in mice fed a high fat diet, G6PD pre-mRNA
      containing intron 11 accumulated within the nucleus, whereas G6PD mature mRNA
      abundance was inhibited 50% or more within the same livers. Transient
      transfection of RNA reporters into primary hepatocyte cultures was used to
      localize the cis-acting RNA element involved in this regulated splicing. Reporter
      RNA produced from constructs containing exon 12 were decreased in amount by
      arachidonic acid. The extent of this decrease paralleled that seen in the
      expression of the endogenous G6PD mRNA. The presence of both exon 12 and a
      neighboring intron within the G6PD reporter RNA was essential for regulation by
      polyunsaturated fatty acid. Inhibition was not dependent on the presence of the
      G6PD polyadenylation signal and the 3'-untranslated region, but substitution with
      the SV40 poly(A) signal attenuated the inhibition by arachidonic acid. Thus, exon
      12 contains a putative splicing regulatory element involved in the inhibition of
      G6PD expression by polyunsaturated fat.

PMID- 12072439
TI  - Phosphatidylinositol 3-kinase activity negatively regulates stability of
      cyclooxygenase 2 mRNA.
AB  - Human alveolar macrophages have both lipopolysaccharide (LPS)-induced and
      constitutive phosphatidylinositol 3-kinase (PI3K) activity. We observed that
      blocking PI3K activity increased release of prostaglandin E2 after LPS exposure,
      and increasing PI3K activity (interleukin-13) decreased release of prostaglandin
      E2 after LPS exposure. This was not because of an effect of PI3K on phospholipase
      2 activity. PI3K inhibition resulted in an increase in cyclooxygenase 2 (COX2)
      protein, mRNA, and mRNA stability. PI3K negatively regulated activation of the
      p38 pathway (p38, MKK3/6, and MAPKAP2), and an active p38 was necessary for COX2
      production. The data suggest that PI3K inhibition of p38 modulates COX2
      expression via destabilization of LPS-induced COX2 mRNA.

PMID- 12072440
TI  - Ceramide mediates age-associated increase in macrophage cyclooxygenase-2
      expression.
AB  - Previously, we showed that macrophages (MO) from old mice have significantly
      higher levels of lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2))
      production than young mice, due to increased cyclooxygenase-2 (COX-2) mRNA
      levels. The aim of the current study was to determine the underlying mechanisms
      of age-associated increase in COX-2 gene expression. The results demonstrate that
      increased COX-2 mRNA expression in the old mice is due to a higher rate of
      transcription rather than increased stability of COX-2 mRNA. Furthermore, the
      results show that LPS-induced ceramide levels from the old mice are significantly
      higher than those of young mice, whereas there is no age-related difference in
      concentration of its down stream metabolite, sphingosine. The addition of
      ceramide in the presence or absence of LPS resulted in a significant increase in
      PGE(2) production in a dose- and time-dependent manner. Inhibition of ceramide
      conversion to sphingosine had no effect on this ceramide-induced effect. The
      ceramide-induced up-regulation in PGE(2) production was mediated through increase
      in COX activity and transcriptional up-regulation of COX-2 mRNA. Collectively,
      these data suggest that the age-associated increase in MO COX-2 mRNA is due to
      transcriptional up-regulation. Furthermore, this increase in transcription is
      mediated by higher cellular ceramide concentration in old MO compared with that
      of young MO.

PMID- 12072441
TI  - 5'-adenosinephosphosulfate lies at a metabolic branch point in mycobacteria.
AB  - Bacterial sulfate assimilation pathways provide for activation of inorganic
      sulfur for the biosynthesis of cysteine and methionine, through either adenosine
      5'-phosphosulfate (APS) or 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as
      intermediates. PAPS is also the substrate for sulfotransferases that produce
      sulfolipids, putative virulence factors, in Mycobacterium tuberculosis such as SL
      1. In this report, genetic complementation using Escherichia coli mutant strains
      deficient in APS kinase and PAPS reductase was used to define the M. tuberculosis
      and Mycobacterium smegmatis CysH enzymes as APS reductases. Consequently, the
      sulfate assimilation pathway of M. tuberculosis proceeds from sulfate through
      APS, which is acted on by APS reductase in the first committed step toward
      cysteine and methionine. Thus, M. tuberculosis most likely produces PAPS for the
      sole use of this organism's sulfotransferases. Deletion of CysH from M. smegmatis
      afforded a cysteine and methionine auxotroph consistent with a metabolic branch
      point centered on APS. In addition, we have redefined the substrate specificity
      of the B. subtilis CysH, formerly designated a PAPS reductase, as an APS
      reductase, based on its ability to complement a mutant E. coli strain deficient
      in APS kinase. Together, these studies show that two conserved sequence motifs,
      CCXXRKXXPL and SXGCXXCT, found in the C termini of all APS reductases, but not in
      PAPS reductases, may be used to predict the substrate specificity of these
      enzymes. A functional domain of the M. tuberculosis CysC protein was cloned and
      expressed in E. coli, confirming the ability of this organism to make PAPS. The
      expression of recombinant M. tuberculosis APS kinase provides a means for the
      discovery of inhibitors of this enzyme and thus of the biosynthesis of SL-1.

PMID- 12072442
TI  - Interaction of human breast fibroblasts with collagen I increases secretion of
      procathepsin B.
AB  - Interactions of stromal and tumor cells with the extracellular matrix may
      regulate expression of proteases including the lysosomal proteases cathepsins B
      and D. In the present study, we determined whether the expression of these two
      proteases in human breast fibroblasts was modulated by interactions with the
      extracellular matrix component, collagen I. Breast fibroblasts were isolated from
      non-malignant breast tissue as well as from tissue surrounding malignant human
      breast tumors. Growth of these fibroblasts on collagen I gels affected cell
      morphology, but not the intracellular localization of vesicles staining for
      cathepsin B or D. Cathepsins B and D levels (mRNA or intracellular protein) were
      not affected in fibroblasts growing on collagen I gels or plastic, nor was
      cathepsin D secreted from these cells. In contrast, protein expression and
      secretion of cathepsin B, primarily procathepsin B, was induced by growth on
      collagen I gels. The induced secretion appeared to be mediated by integrins
      binding to collagen I, as inhibitory antibodies against alpha(1), alpha(2), and
      beta(1) integrin subunits prevented procathepsin B secretion from fibroblasts
      grown on collagen. In addition, procathepsin B secretion was induced when cells
      were plated on beta(1) integrin antibodies. To our knowledge, this is the first
      examination of cathepsin B and D expression and localization in human breast
      fibroblasts and their regulation by a matrix protein. Secretion of the cysteine
      protease procathepsin B from breast fibroblasts may have physiological and
      pathological consequences, as proteases are required for normal development and
      for lactation of the mammary gland, yet can also initiate and accelerate the
      progression of breast cancer.

PMID- 12072443
TI  - Modulation of transforming growth factor beta (TGFbeta)/Smad transcriptional
      responses through targeted degradation of TGFbeta-inducible early gene-1 by human
      seven in absentia homologue.
AB  - Transforming growth factor beta (TGFbeta)-inducible early gene-1 (TIEG1) is a
      Kruppel-like transcription factor that is rapidly induced upon TGFbeta treatment.
      TIEG1 promotes TGFbeta/Smad signaling by down-regulating negative feedback
      through the inhibitory Smad7. In this report, we describe the identification of
      an E3 ubiquitin ligase, Seven in Absentia homologue-1 (SIAH1), as a TIEG1
      interacting protein. We show that TIEG1 and SIAH1 interact through an amino
      terminal domain of TIEG1. Co-expression of SIAH1 results in proteasomal
      degradation of TIEG1 but not of the related factor TIEG2. Importantly, co
      expression of SIAH1 completely reverses repression of Smad7 promoter activity by
      TIEG1. Furthermore, overexpression of a dominant negative SIAH1 stabilizes TIEG1
      and synergizes with TIEG1 to enhance TGFbeta/Smad-dependent transcriptional
      activation. These findings suggest a novel mechanism whereby the ability of
      TGFbeta to modulate gene transcription may be regulated by proteasomal
      degradation of the downstream effector TIEG1 through the SIAH pathway. In this
      manner, turnover of TIEG1 may serve to limit the duration and/or magnitude of
      TGFbeta responses.

PMID- 12072444
TI  - DsbB catalyzes disulfide bond formation de novo.
AB  - DsbA and DsbB are responsible for disulfide bond formation. DsbA is the direct
      donor of disulfides, and DsbB oxidizes DsbA. DsbB has the unique ability to
      generate disulfides by quinone reduction. It is thought that DsbB oxidizes DsbA
      via thiol disulfide exchange. In this mechanism, a disulfide is formed across the
      N-terminal pair of cysteines (Cys-41/Cys-44) in DsbB by quinone reduction. This
      disulfide is then transferred on to the second pair of cysteine residues in DsbB
      (Cys-104/Cys-130) and then finally transferred to DsbA. We have shown here the
      redox potential of the two disulfides in DsbB are -271 and -284 mV, respectively,
      and considerably less oxidizing than the disulfide of DsbA at -120 mV. In
      addition, we have found the Cys-104/Cys-130 disulfide of DsbB to actually be a
      substrate for DsbA in vitro. These findings indicate that the disulfides in DsbB
      are unsuitable to function as the oxidant of DsbA. Furthermore, we have shown
      that mutants in DsbB that lack either pair or all of its cysteines are also
      capable of oxidizing DsbA. These unexpected findings raise the possibility that
      the oxidation of DsbA by DsbB does not occur via thiol disulfide exchange as is
      widely assumed but rather, directly via quinone reduction.

PMID- 12072446
TI  - Cytokine and cytokine receptor pleiotropy and redundancy.

PMID- 12072445
TI  - Kruppel-like zinc fingers bind to nuclear import proteins and are required for
      efficient nuclear localization of erythroid Kruppel-like factor.
AB  - Erythroid Kruppel-like Factor (EKLF/KLF-1) is an erythroid-specific transcription
      factor that contains three C(2)H(2) zinc fingers and is required for correct
      chromatin structure and expression of the beta-globin locus. However, regions
      within the EKLF protein that serve as signals for its nuclear localization and
      the proteins that may enable it to become localized are unknown. Two approaches
      were used to address these issues. First, green fluorescent protein or pyruvate
      kinase was fused to EKLF domains, and localization was monitored and quantitated
      by confocal microscopy. Two necessary and sufficient nuclear localization signals
      (NLSs) were identified: one (NLS1) adjacent to the zinc finger DNA binding domain
      within a highly basic stretch of amino acids (275-296), and another more
      efficient signal (NLS2) within the zinc finger domain itself (amino acids 293
      376). Interestingly, each zinc finger contributes to the overall effectiveness of
      NLS2 and requires an intact finger structure. Second, each NLS was tested in
      vitro for binding to importin proteins. Surprisingly, both EKLF NLSs, but
      principally the zinc finger domain, bind importin alpha and importin beta. These
      findings demonstrate that two nuclear localization signals target EKLF to the
      nucleus and suggest this transport relies primarily on a novel zinc
      finger/importin protein interaction.

PMID- 12072447
TI  - Richard Goldschmidt and the crossing-over controversy.

PMID- 12072448
TI  - A domain of RecC required for assembly of the regulatory RecD subunit into the
      Escherichia coli RecBCD holoenzyme.
AB  - The heterotrimeric RecBCD enzyme of Escherichia coli is required for the major
      pathway of double-strand DNA break repair and genetic exchange. Assembled as a
      heterotrimer, the enzyme has potent nuclease and helicase activity. Analysis of
      recC nonsense and deletion mutations revealed that the C terminus of RecC is
      required for assembly of the RecD subunit into RecBCD holoenzyme but not for
      recombination proficiency; the phenotype of these mutations mimics that of recD
      deletion mutations. Partial proteolysis of purified RecC polypeptide yielded a C
      terminal fragment that corresponds to the RecD-interaction domain. RecD is
      essential for nuclease activity, regulation by the recombination hotspot Chi, and
      high affinity for DNA ends. The RecC-RecD interface thus appears critical for the
      regulation of RecBCD enzyme via the assembly and, we propose, disassembly or
      conformational change of the RecD subunit.

PMID- 12072449
TI  - Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian
      ATM and ATR genes.
AB  - In eukaryotes, a family of related protein kinases (the ATM family) is involved
      in regulating cellular responses to DNA damage and telomere length. In the yeast
      Saccharomyces cerevisiae, two members of this family, TEL1 and MEC1, have
      functionally redundant roles in both DNA damage repair and telomere length
      regulation. Strains with mutations in both genes are very sensitive to DNA
      damaging agents, have very short telomeres, and undergo cellular senescence. We
      find that strains with the double mutant genotype also have approximately 80-fold
      increased rates of mitotic recombination and chromosome loss. In addition, the
      tel1 mec1 strains have high rates of telomeric fusions, resulting in
      translocations, dicentrics, and circular chromosomes. Similar chromosome
      rearrangements have been detected in mammalian cells with mutations in ATM
      (related to TEL1) and ATR (related to MEC1) and in mammalian cells that approach
      cell crisis.

PMID- 12072450
TI  - Spt3 plays opposite roles in filamentous growth in Saccharomyces cerevisiae and
      Candida albicans and is required for C. albicans virulence.
AB  - Spt3 of Saccharomyces cerevisiae is required for the normal transcription of many
      genes in vivo. Past studies have shown that Spt3 is required for both mating and
      sporulation, two events that initiate when cells are at G(1)/START. We now show
      that Spt3 is needed for two other events that begin at G(1)/START, diploid
      filamentous growth and haploid invasive growth. In addition, Spt3 is required for
      normal expression of FLO11, a gene required for filamentous growth, although this
      defect is not the sole cause of the spt3Delta/spt3Delta filamentous growth
      defect. To extend our studies of Spt3's role in filamentous growth to the
      pathogenic yeast Candida albicans, we have identified the C. albicans SPT3 gene
      and have studied its role in C. albicans filamentous growth and virulence.
      Surprisingly, C. albicans spt3Delta/spt3Delta mutants are hyperfilamentous, the
      opposite phenotype observed for S. cerevisiae spt3Delta/spt3Delta mutants.
      Furthermore, C. albicans spt3Delta/spt3Delta mutants are avirulent in mice. These
      experiments demonstrate that Spt3 plays important but opposite roles in
      filamentous growth in S. cerevisiae and C. albicans.

PMID- 12072451
TI  - Overlapping roles of the spindle assembly and DNA damage checkpoints in the cell
      cycle response to altered chromosomes in Saccharomyces cerevisiae.
AB  - The MAD2-dependent spindle checkpoint blocks anaphase until all chromosomes have
      achieved successful bipolar attachment to the mitotic spindle. The DNA damage and
      DNA replication checkpoints block anaphase in response to DNA lesions that may
      include single-stranded DNA and stalled replication forks. Many of the same
      conditions that activate the DNA damage and DNA replication checkpoints also
      activated the spindle checkpoint. The mad2Delta mutation partially relieved the
      arrest responses of cells to mutations affecting the replication proteins Mcm3p
      and Pol1p. Thus a previously unrecognized aspect of spindle checkpoint function
      may be to protect cells from defects in DNA replication. Furthermore, in cells
      lacking either the DNA damage or the DNA replication checkpoints, the spindle
      checkpoint contributed to the arrest responses of cells to the DNA-damaging agent
      methyl methanesulfonate, the replication inhibitor hydroxyurea, and mutations
      affecting Mcm2p and Orc2p. Thus the spindle checkpoint was sensitive to a wider
      range of chromosomal perturbations than previously recognized. Finally, the DNA
      replication checkpoint did not contribute to the arrests of cells in response to
      mutations affecting ORC, Mcm proteins, or DNA polymerase delta. Thus the
      specificity of this checkpoint may be more limited than previously recognized.

PMID- 12072452
TI  - Replication protein A is required for meiotic recombination in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae, meiotic recombination is initiated by transient DNA
      double-stranded breaks (DSBs). These DSBs undergo a 5' --> 3' resection to
      produce 3' single-stranded DNA ends that serve to channel DSBs into the RAD52
      recombinational repair pathway. In vitro studies strongly suggest that several
      proteins of this pathway--Rad51, Rad52, Rad54, Rad55, Rad57, and replication
      protein A (RPA)--play a role in the strand exchange reaction. Here, we report a
      study of the meiotic phenotypes conferred by two missense mutations affecting the
      largest subunit of RPA, which are localized in the protein interaction domain
      (rfa1-t11) and in the DNA-binding domain (rfa1-t48). We find that both mutant
      diploids exhibit reduced sporulation efficiency, very poor spore viability, and a
      10- to 100-fold decrease in meiotic recombination. Physical analyses indicate
      that both mutants form normal levels of meiosis-specific DSBs and that the broken
      ends are processed into 3'-OH single-stranded tails, indicating that the RPA
      complex present in these rfa1 mutants is functional in the initial steps of
      meiotic recombination. However, the 5' ends of the broken fragments undergo
      extensive resection, similar to what is observed in rad51, rad52, rad55, and
      rad57 mutants, indicating that these RPA mutants are defective in the repair of
      the Spo11-dependent DSBs that initiate homologous recombination during meiosis.

PMID- 12072453
TI  - A molecular genetic dissection of the evolutionarily conserved N terminus of
      yeast Rad52.
AB  - Rad52 is a DNA-binding protein that stimulates the annealing of complementary
      single-stranded DNA. Only the N terminus of Rad52 is evolutionarily conserved; it
      contains the core activity of the protein, including its DNA-binding activity. To
      identify amino acid residues that are important for Rad52 function(s), we
      systematically replaced 76 of 165 amino acid residues in the N terminus with
      alanine. These substitutions were examined for their effects on the repair of
      gamma-ray-induced DNA damage and on both interchromosomal and direct repeat
      heteroallelic recombination. This analysis identified five regions that are
      required for efficient gamma-ray damage repair or mitotic recombination. Two
      regions, I and II, also contain the classic mutations, rad52-2 and rad52-1,
      respectively. Interestingly, four of the five regions contain mutations that
      impair the ability to repair gamma-ray-induced DNA damage yet still allow mitotic
      recombinants to be produced at rates that are similar to or higher than those
      obtained with wild-type strains. In addition, a new class of separation-of
      function mutation that is only partially deficient in the repair of gamma-ray
      damage, but exhibits decreased mitotic recombination similar to rad52 null
      strains, was identified. These results suggest that Rad52 protein acts
      differently on lesions that occur spontaneously during the cell cycle than on
      those induced by gamma-irradiation.

PMID- 12072454
TI  - Volatile anesthetics affect nutrient availability in yeast.
AB  - Volatile anesthetics affect all cells and tissues tested, but their mechanisms
      and sites of action remain unknown. To gain insight into the cellular activities
      of anesthetics, we have isolated genes that, when overexpressed, render
      Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of
      these genes, WAK3/TAT1, encodes a permease that transports amino acids including
      leucine and tryptophan, for which our wild-type strain is auxotrophic. This
      suggests that availability of amino acids may play a key role in anesthetic
      response. Multiple lines of evidence support this proposal: (i) Deletion or
      overexpression of permeases that transport leucine and/or tryptophan alters
      anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii)
      altered concentrations of leucine and tryptophan in the medium affect anesthetic
      response; and (iv) uptake of leucine and tryptophan is inhibited during
      anesthetic exposure. Not all amino acids are critical for this response since we
      find that overexpression of the lysine permease does not affect anesthetic
      sensitivity. These findings are consistent with models in which anesthetics have
      a physiologically important effect on availability of specific amino acids by
      altering function of their permeases. In addition, we show that there is a
      relationship between nutrient availability and ubiquitin metabolism in this
      response.

PMID- 12072456
TI  - Gene overexpression as a tool for identifying new trans-acting factors involved
      in translation termination in Saccharomyces cerevisiae.
AB  - In eukaryotes, translation termination is dependent on the availability of both
      release factors, eRF1 and eRF3; however, the precise mechanisms involved remain
      poorly understood. In particular, the fact that the phenotype of release factor
      mutants is pleiotropic could imply that other factors and interactions are
      involved in translation termination. To identify unknown elements involved in
      this process, we performed a genetic screen using a reporter strain in which a
      leaky stop codon is inserted in the lacZ reporter gene, attempting to isolate
      factors modifying termination efficiency when overexpressed. Twelve suppressors
      and 11 antisuppressors, increasing or decreasing termination readthrough,
      respectively, were identified and analyzed for three secondary phenotypes often
      associated with translation mutations: thermosensitivity, G418 sensitivity, and
      sensitivity to osmotic pressure. Interestingly, among these candidates, we
      identified two genes, SSO1 and STU2, involved in protein transport and spindle
      pole body formation, respectively, suggesting puzzling connections with the
      translation termination process.

PMID- 12072457
TI  - IBD2 encodes a novel component of the Bub2p-dependent spindle checkpoint in the
      budding yeast Saccharomyces cerevisiae.
AB  - During mitosis, genomic integrity is maintained by the proper coordination of
      mitotic events through the spindle checkpoint. The bifurcated spindle checkpoint
      blocks cell cycle progression at metaphase by monitoring unattached kinetochores
      and inhibits mitotic exit in response to the incorrect orientation of the mitotic
      spindle. Bfa1p is a spindle checkpoint regulator of budding yeast in the Bub2p
      checkpoint pathway for proper mitotic exit. We have isolated a novel Bfa1p
      interacting protein named Ibd2p in the budding yeast Saccharomyces cerevisiae. We
      found that IBD2 (Inhibition of Bud Division 2) is not an essential gene but its
      deletion mutant proceeded through the cell cycle in the presence of microtubule
      destabilizing drugs, thereby inducing a sharp decrease in viability. In addition,
      overexpression of Mps1p caused partial mitotic arrest in ibd2Delta as well as in
      bub2Delta, suggesting that IBD2 encodes a novel component of the spindle
      checkpoint downstream of MPS1. Overexpression of Ibd2p induced mitotic arrest
      with increased levels of Clb2p in wild type and mad2Delta, but not in deletion
      mutants of BUB2 and BFA1. Pds1p was also stabilized by the overexpression of
      Ibd2p in wild-type cells. The mitotic arrest defects observed in ibd2Delta in the
      presence of nocodazole were restored by additional copies of BUB2, BFA1, and
      CDC5, whereas an extra copy of IBD2 could not rescue the mitotic arrest defects
      of bub2Delta and bfa1Delta. The mitotic arrest defects of ibd2Delta were not
      recovered by MAD2, or vice versa. Analysis of the double mutant combinations
      ibd2Deltamad2Delta, ibd2Deltabub2Delta, and ibd2Deltadyn1Delta showed that IBD2
      belongs to the BUB2 epistasis group. Taken together, these data demonstrate that
      IBD2 encodes a novel component of the BUB2-dependent spindle checkpoint pathway
      that functions upstream of BUB2 and BFA1.

PMID- 12072455
TI  - Yeast RSC function is required for organization of the cellular cytoskeleton via
      an alternative PKC1 pathway.
AB  - RSC is a 15-protein ATP-dependent chromatin-remodeling complex related to Snf
      Swi, the prototypical ATP-dependent nucleosome remodeler in budding yeast.
      Despite insight into the mechanism by which purified RSC remodels nucleosomes,
      little is known about the chromosomal targets or cellular pathways in which RSC
      acts. To better understand the cellular function of RSC, a screen was undertaken
      for gene dosage suppressors of sth1-3ts, a temperature-sensitive mutation in
      STH1, which encodes the essential ATPase subunit. Slg1p and Mid2p, two type I
      transmembrane stress sensors of cell wall integrity that function upstream of
      protein kinase C (Pkc1p), were identified as multicopy suppressors of sth1-3ts
      cells. Although the sth1-3ts mutant exhibits defects characteristic of PKC1
      pathway mutants (caffeine and staurosporine sensitivities and an osmoremedial
      phenotype), only upstream components and not downstream effectors of the PKC1-MAP
      kinase pathway can suppress defects conferred by sth1-3ts, suggesting that RSC
      functions in an alternative PKC1-dependent pathway. Moreover, sth1-3ts cells
      display defects in actin cytoskeletal rearrangements and are hypersensitive to
      the microtubule depolymerizing drug, TBZ; both of these defects can be corrected
      by the high-copy suppressors. Together, these data reveal an important functional
      connection between the RSC remodeler and PKC1-dependent signaling in regulating
      the cellular architecture.

PMID- 12072458
TI  - Expression-state boundaries in the mating-type region of fission yeast.
AB  - A transcriptionally silent chromosomal domain is found in the mating-type region
      of fission yeast. Here we show that this domain is delimited by 2-kb inverted
      repeats, IR-L and IR-R. IR-L and IR-R prevent the expansion of transcription
      permissive chromatin into the silenced region and that of silenced chromatin into
      the expressed region. Their insulator activity is partially orientation
      dependent. The silencing defects that follow deletion or inversion of IR-R are
      suppressed by high dosage of the chromodomain protein Swi6. Combining chromosomal
      deletions and Swi6 overexpression shows that IR-L and IR-R provide firm borders
      in a region where competition between silencing and transcriptional competence
      occurs. IR-R possesses autonomously replicating sequence (ARS) activity, leading
      to a model where replication factors, or replication itself, participate in
      boundary formation.

PMID- 12072460
TI  - Multilocus self-recognition systems in fungi as a cause of trans-species
      polymorphism.
AB  - Trans-species polymorphism, meaning the presence of alleles in different species
      that are more similar to each other than they are to alleles in the same species,
      has been found at loci associated with vegetative incompatibility in filamentous
      fungi. If individuals differ at one or more of these loci (termed het for
      heterokaryon), they cannot form stable heterokaryons after vegetative fusion. At
      the het-c locus in Neurospora crassa and related species there is clear evidence
      of trans-species polymorphism: three alleles have persisted for approximately 30
      million years. We analyze a population genetic model of multilocus vegetative
      incompatibility and find the conditions under which trans-species polymorphism
      will occur. In the model, several unlinked loci determine the vegetative
      compatibility group (VCG) of an individual. Individuals of different VCGs fail to
      form productive heterokaryons, while those of the same VCG form viable
      heterokaryons. However, viable heterokaryon formation between individuals of the
      same VCG results in a loss in fitness, presumably via transfer of infectious
      agents by hyphal fusion or exploitation by aggressive genotypes. The result is a
      form of balancing selection on all loci affecting an individual's VCG. We analyze
      this model by making use of a Markov chain/strong selection, weak mutation (SSWM)
      approximation. We find that trans-species polymorphism of the type that has been
      found at the het-c locus is expected to occur only when the appearance of new
      incompatibility alleles is strongly constrained, because the rate of mutation to
      such alleles is very low, because the number of possible incompatibility alleles
      at each locus is restricted, or because the number of incompatibility loci is
      limited.

PMID- 12072459
TI  - Mutational analysis of the gephyrin-related molybdenum cofactor biosynthetic gene
      cnxE from the lower eukaryote Aspergillus nidulans.
AB  - We report the identification of a number of mutations that result in amino acid
      replacements (and their phenotypic characterization) in either the MogA-like
      domain or domains 2 and 3 of the MoeA-like region of the Aspergillus nidulans
      cnxE gene. These domains are functionally required since mutations that result in
      amino acid substitutions in any one domain lead to the loss or to a substantial
      reduction in all three identified molybdoenzyme activities (i.e., nitrate
      reductase, xanthine dehydrogenase, and nicotinate hydroxylase). Certain cnxE
      mutants that show partial growth with nitrate as the nitrogen source in contrast
      do not grow on hypoxanthine or nicotinate. Complementation between mutants
      carrying lesions in the MogA-like domain or the MoeA-like region, respectively,
      most likely occurs at the protein level. A homology model of CnxE based on the
      dimeric structure of E. coli MoeA is presented and the position of inactivating
      mutations (due to amino acid replacements) in the MoeA-like functional region of
      the CnxE protein is mapped to this model. Finally, the activity of nicotinate
      hydroxylase, unlike that of nitrate reductase and xanthine dehydrogenase, is not
      restored in cnxE mutants grown in the presence of excess molybdate.

PMID- 12072461
TI  - N-ethylmaleimide-sensitive factor is required to organize functional exocytotic
      microdomains in paramecium.
AB  - In exocytosis, secretory granules contact plasma membrane at sites where
      microdomains can be observed, which are sometimes marked by intramembranous
      particle arrays. Such arrays are particularly obvious when membrane fusion is
      frozen at a subterminal stage, e.g., in neuromuscular junctions and ciliate
      exocytotic sites. In Paramecium, a genetic approach has shown that the "rosettes"
      of intramembranous particles are essential for stimulated exocytosis of secretory
      granules, the trichocysts. The identification of two genes encoding the N
      ethylmaleimide-sensitive factor (NSF), a chaperone ATPase involved in organelle
      docking, prompted us to analyze its potential role in trichocyst exocytosis using
      a gene-silencing strategy. Here we show that NSF deprivation strongly interferes
      with rosette assembly but does not disturb the functioning of exocytotic sites
      already formed. We conclude that rosette organization involves ubiquitous
      partners of the fusion machinery and discuss where NSF could intervene in this
      mechanism.

PMID- 12072462
TI  - Frequent germline mutations and somatic repeat instability in DNA mismatch-repair
      deficient Caenorhabditis elegans.
AB  - Mismatch-repair-deficient mutants were initially recognized as mutation-prone
      derivatives of bacteria, and later mismatch repair deficiency was found to
      predispose humans to colon cancers (HNPCC). We generated mismatch-repair
      deficient Caenorhabditis elegans by deleting the msh-6 gene and analyzed the
      fidelity of transmission of genetic information to subsequent generations. msh-6
      defective animals show an elevated level of spontaneous mutants in both the male
      and female germline; also repeated DNA tracts are unstable. To monitor DNA repeat
      instability in somatic tissue, we developed a sensitive system, making use of
      heat-shock promoter-driven lacZ transgenes, but with a repeat that puts this
      reporter gene out of frame. In genetic msh-6-deficient animals lacZ+ patches are
      observed as a result of somatic repeat instability. RNA interference by feeding
      wild-type animals dsRNA homologous to msh-2 or msh-6 also resulted in somatic DNA
      instability, as well as in germline mutagenesis, indicating that one can use C.
      elegans as a model system to discover genes involved in maintaining DNA stability
      by large-scale RNAi screens.

PMID- 12072464
TI  - The genetic basis of the interspecific differences in wing size in Nasonia
      (Hymenoptera; Pteromalidae): major quantitative trait loci and epistasis.
AB  - There is a 2.5-fold difference in male wing size between two haplodiploid insect
      species, Nasonia vitripennis and N. giraulti. The haploidy of males facilitated a
      full genomic screen for quantitative trait loci (QTL) affecting wing size and the
      detection of epistatic interactions. A QTL analysis of the interspecific wing
      size difference revealed QTL with major effects and epistatic interactions among
      loci affecting the trait. We analyzed 178 hybrid males and initially found two
      major QTL for wing length, one for wing width, three for a normalized wing-size
      variable, and five for wing seta density. One QTL for wing width explains 38.1%
      of the phenotypic variance, and the same QTL explains 22% of the phenotypic
      variance in normalized wing size. This corresponds to a region previously
      introgressed from N. giraulti into N. vitripennis that accounts for 44% of the
      normalized wing-size difference between the species. Significant epistatic
      interactions were also found that affect wing size and density of setae on the
      wing. Screening for pairwise epistatic interactions between loci on different
      linkage groups revealed four additional loci for wing length and four loci for
      normalized wing size that were not detected in the original QTL analysis. We
      propose that the evolution of smaller wings in N. vitripennis males is primarily
      the result of major mutations at few genomic regions and involves epistatic
      interactions among some loci.

PMID- 12072463
TI  - Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life
      span of adult Drosophila melanogaster.
AB  - A transgenic system ("FLP-out") based on yeast FLP recombinase allowed induced
      overexpression of MnSOD enzyme in adult Drosophila melanogaster. With FLP-out a
      brief heat pulse (HP) of young, adult flies triggered the rearrangement and
      subsequent expression of a MnSOD transgene throughout the adult life span.
      Control (no HP) and overexpressing (HP) flies had identical genetic backgrounds.
      The amount of MnSOD enzyme overexpression achieved varied among six independent
      transgenic lines, with increases up to 75%. Life span was increased in proportion
      to the increase in enzyme. Mean life span was increased by an average of 16%,
      with some lines showing 30-33% increases. Maximum life span was increased by an
      average of 15%, with one line showing as much as 37% increase. Simultaneous
      overexpression of catalase with MnSOD had no added benefit, consistent with
      previous observations that catalase is present in excess in the adult fly with
      regard to life span. Cu/ZnSOD overexpression also increases mean and maximum life
      span. For both MnSOD and Cu/ZnSOD lines, increased life span was not associated
      with decreased metabolic activity, as measured by O2 consumption.

PMID- 12072465
TI  - An analysis using the hobo genetic system reveals that combinatorial signaling by
      the Dpp and Wg pathways regulates dpp expression in leading edge cells of the
      dorsal ectoderm in Drosophila melanogaster.
AB  - Our laboratory has contributed to the development of a genetic system based upon
      the hobo transposable element in Drosophila melanogaster. We recently reported
      that hobo, like the better-known P element, is capable of local transposition. In
      that study, we mobilized a hobo enhancer trap vector and generated two unique
      alleles of decapentaplegic (dpp), a transforming growth factor-beta family member
      with numerous roles during development. Here we report a detailed study of one of
      those alleles (dpp(F11)). To our knowledge, this is the first application of the
      hobo genetic system to understanding developmental processes. First, we
      demonstrate that lacZ expression from the dpp(F11) enhancer trap accurately
      reflects dpp mRNA accumulation in leading edge cells of the dorsal ectoderm. Then
      we show that combinatorial signaling by the Wingless (Wg) pathway, the Dpp
      pathway, and the transcriptional coactivator Nejire (CBP/p300) regulates dpp(F11)
      expression in these cells. Our analysis of dpp(F11) suggests a model for the
      integration of Wg and Dpp signals that may be applicable to other developmental
      systems. Our analysis also illustrates several new features of the hobo genetic
      system and highlights the value of hobo, as an alternative to P, in addressing
      developmental questions.

PMID- 12072469
TI  - Transvection and silencing of the Scr homeotic gene of Drosophila melanogaster.
AB  - The Sex combs reduced (Scr) gene specifies the identities of the labial and first
      thoracic segments in Drosophila melanogaster. In imaginal cells, some Scr
      mutations allow cis-regulatory elements on one chromosome to stimulate expression
      of the promoter on the homolog, a phenomenon that was named transvection by Ed
      Lewis in 1954. Transvection at the Scr gene is blocked by rearrangements that
      disrupt pairing, but is zeste independent. Silencing of the Scr gene in the
      second and third thoracic segments, which requires the Polycomb group proteins,
      is disrupted by most chromosomal aberrations within the Scr gene. Some
      chromosomal aberrations completely derepress Scr even in the presence of normal
      levels of all Polycomb group proteins. On the basis of the pattern of chromosomal
      aberrations that disrupt Scr gene silencing, we propose a model in which two cis
      regulatory elements interact to stabilize silencing of any promoter or cis
      regulatory element physically between them. This model also explains the
      anomalous behavior of the Scx allele of the flanking homeotic gene, Antennapedia.
      This allele, which is associated with an insertion near the Antennapedia P1
      promoter, inactivates the Antennapedia P1 and P2 promoters in cis and derepresses
      the Scr promoters both in cis and on the homologous chromosome.

PMID- 12072466
TI  - rugose (rg), a Drosophila A kinase anchor protein, is required for retinal
      pattern formation and interacts genetically with multiple signaling pathways.
AB  - In the developing Drosophila eye, cell fate determination and pattern formation
      are directed by cell-cell interactions mediated by signal transduction cascades.
      Mutations at the rugose locus (rg) result in a rough eye phenotype due to a
      disorganized retina and aberrant cone cell differentiation, which leads to
      reduction or complete loss of cone cells. The cone cell phenotype is sensitive to
      the level of rugose gene function. Molecular analyses show that rugose encodes a
      Drosophila A kinase anchor protein (DAKAP 550). Genetic interaction studies show
      that rugose interacts with the components of the EGFR- and Notch-mediated
      signaling pathways. Our results suggest that rg is required for correct retinal
      pattern formation and may function in cell fate determination through its
      interactions with the EGFR and Notch signaling pathways.

PMID- 12072468
TI  - Ectopic expression of the Drosophila Cdk1 inhibitory kinases, Wee1 and Myt1,
      interferes with the second mitotic wave and disrupts pattern formation during eye
      development.
AB  - Wee1 kinases catalyze inhibitory phosphorylation of the mitotic regulator Cdk1,
      preventing mitosis during S phase and delaying it in response to DNA damage or
      developmental signals during G2. Unlike yeast, metazoans have two distinct Wee1
      like kinases, a nuclear protein (Wee1) and a cytoplasmic protein (Myt1). We have
      isolated the genes encoding Drosophila Wee1 and Myt1 and are using genetic
      approaches to dissect their functions during normal development. Overexpression
      of Dwee1 or Dmyt1 during eye development generates a rough adult eye phenotype.
      The phenotype can be modified by altering the gene dosage of known regulators of
      the G2/M transition, suggesting that we could use these transgenic strains in
      modifier screens to identify potential regulators of Wee1 and Myt1. To confirm
      this idea, we tested a collection of deletions for loci that can modify the eye
      overexpression phenotypes and identified several loci as dominant modifiers.
      Mutations affecting the Delta/Notch signaling pathway strongly enhance a GMR
      Dmyt1 eye phenotype but do not affect a GMR-Dwee1 eye phenotype, suggesting that
      Myt1 is potentially a downstream target for Notch activity during eye
      development. We also observed interactions with p53, which suggest that Wee1 and
      Myt1 activity can block apoptosis.

PMID- 12072467
TI  - Efficient repair of DNA breaks in Drosophila: evidence for single-strand
      annealing and competition with other repair pathways.
AB  - We show evidence that DNA double-strand breaks induced in the Drosophila germ
      line can be repaired very efficiently by the single-strand annealing (SSA)
      mechanism. A double-strand break was made between two copies of a 1290-bp direct
      repeat by mobilizing a P transposon. In >80% of the progeny that acquired this
      chromosome, repair resulted in loss of the P element and loss of one copy of the
      repeat, as observed in SSA. The frequency of this repair was much greater than
      seen for gene conversion using an allelic template, which is only approximately
      7%. A similar structure, but with a smaller duplication of only 158 bp, also
      yielded SSA-like repair events, but at a reduced frequency, and gave rise to some
      products by repair pathways other than SSA. The 1290-bp repeats carried two
      sequence polymorphisms that were examined in the products. The allele nearest to
      a nick in the putative heteroduplex intermediate was lost most often. This bias
      is predicted by the SSA model, although other models could account for it. We
      conclude that SSA is the preferred repair pathway in Drosophila for DNA breaks
      between sequence repeats, and it competes with gene conversion by the synthesis
      dependent strand annealing (SDSA) pathway.

PMID- 12072470
TI  - A mutational analysis of dishevelled in Drosophila defines novel domains in the
      dishevelled protein as well as novel suppressing alleles of axin.
AB  - Drosophila dishevelled (dsh) functions in two pathways: it is necessary to
      transduce Wingless (Wg) signaling and it is required in planar cell polarity. To
      learn more about how Dsh can discriminate between these functions, we performed
      genetic screens to isolate additional dsh alleles and we examined the potential
      role of protein phosphorylation by site-directed mutagenesis. We identified two
      alleles with point mutations in the Dsh DEP domain that specifically disrupt
      planar polarity signaling. When positioned in the structure of the DEP domain,
      these mutations are located close to each other and to a previously identified
      planar polarity mutation. In addition to the requirement for the DEP domain, we
      found that a cluster of potential phosphorylation sites in a binding domain for
      the protein kinase PAR-1 is also essential for planar polarity signaling. To
      identify regions of dsh that are necessary for Wg signaling, we screened for
      mutations that modified a GMR-GAL4;UAS-dsh overexpression phenotype in the eye.
      We recovered many alleles of the transgene containing missense mutations,
      including mutations in the DIX domain and in the DEP domain, the latter group
      mapping separately from the planar polarity mutations. In addition, several
      transgenes had mutations within a domain containing a consensus sequence for an
      SH3-binding protein. We also recovered second-site-suppressing mutations in axin,
      mapping at a region that may specifically interact with overexpressed Dsh.

PMID- 12072473
TI  - Effective size of fluctuating salmon populations.
AB  - Pacific salmon are semelparous but have overlapping year classes, which presents
      special challenges for the application of standard population genetics theory to
      these species. This article examines the relationship between the effective
      number of breeders per year (N(b)) and single-generation and multigeneration
      effective population size (N(e)) in salmon populations that fluctuate in size. A
      simple analytical model is developed that allows calculation of N(e) on the basis
      of the number of spawners in individual years and their reproductive contribution
      (productivity) to the next generation. Application of the model to a 36-year time
      series of data for a threatened population of Snake River chinook salmon suggests
      that variation in population dynamic processes across years reduced the
      multigeneration N(e) by approximately 40-60%, and reductions may have been
      substantially greater within some generations. These reductions are comparable in
      magnitude to, and in addition to, reductions in N(b) within a year due to unequal
      sex ratio and nonrandom variation in reproductive success. Computer simulations
      suggest that the effects of variable population dynamics on N(e) observed in this
      dataset are not unexpected for species with a salmon life history, as random
      variation in productivity can lead to similar results.

PMID- 12072472
TI  - Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica
      identifies two loci that confer high-level resistance to the fumigant phosphine.
AB  - High levels of inheritable resistance to phosphine in Rhyzopertha dominica have
      recently been detected in Australia and in an effort to isolate the genes
      responsible for resistance we have used random amplified DNA fingerprinting (RAF)
      to produce a genetic linkage map of R. dominica. The map consists of 94 dominant
      DNA markers with an average distance between markers of 4.6 cM and defines nine
      linkage groups with a total recombination distance of 390.1 cM. We have
      identified two loci that are responsible for high-level resistance. One provides
      approximately 50x resistance to phosphine while the other provides 12.5x
      resistance and in combination, the two genes act synergistically to provide a
      resistance level 250x greater than that of fully susceptible beetles. The haploid
      genome size has been determined to be 4.76 x 10(8) bp, resulting in an average
      physical distance of 1.2 Mbp per map unit. No recombination has been observed
      between either of the two resistance loci and their adjacent DNA markers in a
      population of 44 fully resistant F5 individuals, which indicates that the genes
      are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers.

PMID- 12072471
TI  - P elements inserted in the vicinity of or within the Drosophila snRNP SmD3 gene
      nested in the first intron of the Ornithine Decarboxylase Antizyme gene affect
      only the expression of SmD3.
AB  - The Drosophila gene for snRNP SmD3 (SmD3) is contained in reverse orientation
      within the first intron of the Ornithine Decarboxylase Antizyme (AZ) gene.
      Previous studies show that two closely linked P elements cause the gutfeeling
      phenotype characterized by embryonic lethality and aberrant neuronal and muscle
      cell differentiation. However, the exact nature of the gene(s) affected in the
      gutfeeling phenotype remained unknown. This study shows that a series of P
      inserts located within the 5'-untranslated region (5'-UTR) of SmD3 or its
      promoter affects only the expression of SmD3. Our analysis reveals that the
      gutfeeling phenotype associated with P elements inserted in the 5'-UTR of SmD3
      results from amorphic or strongly hypomorphic mutations. In contrast, P inserts
      in the SmD3 promoter region reduce the expression of SmD3 without abolishing it
      and produce larval lethality with overgrown imaginal discs, brain hemispheres,
      and hematopoietic organs. The lethality of these mutations could be rescued by an
      SmD3+ transgene. Finally, inactivation of AZ was obtained by complementing with
      SmD3+ the deficiency Df(2R)guf(lex47) that uncovers both SmD3 and AZ.
      Interestingly, AZ inactivation causes a new phenotype characterized by late
      larval lethality and atrophy of the brain, imaginal discs, hematopoietic organs,
      and salivary glands.

PMID- 12072474
TI  - Transposon insertions in the promoter of the Zea mays a1 gene differentially
      affect transcription by the Myb factors P and C1.
AB  - The understanding of control of gene regulation in higher eukaryotes relies
      heavily on results derived from non-in vivo studies, but rarely can the
      significance of these approximations be established in vivo. Here, we
      investigated the effect of Mutator and Spm insertions on the expression of the
      flavonoid biosynthetic gene a1, independently regulated by the transcription
      factors C1 and P. The a1-mum2 and a1-m2 alleles carry Mu1 and Spm insertions,
      respectively, in a cis-element (ARE) of unknown function located between the P-
      and C1-binding sites. We show that the insertions of Mu1 and Spm similarly
      influence the expression of a1 controlled by C1 or P. The P-controlled a1
      expression in a1-m2 is Spm dependent, and the mutant phenotype of a1-mum2 is
      suppressed in the pericarp in the absence of the autonomous MuDR element.
      Footprints within the ARE affect the regulation of a1 by C1 and P differently,
      providing evidence that these factors control a1 expression using distinct cis
      acting regulatory elements. Together, our findings contribute significantly to
      one of the best-described plant regulatory systems, while stressing the need to
      complement with in vivo experiments current approaches used for the study of
      control of gene expression.

PMID- 12072475
TI  - Role of salicylic acid and NIM1/NPR1 in race-specific resistance in arabidopsis.
AB  - Salicylic acid (SA) and the NIM1/NPR1 protein have both been demonstrated to be
      required for systemic acquired resistance (SAR) and implicated in expression of
      race-specific resistance. In this work, we analyzed the role that each of these
      molecules play in the resistance response triggered by members of two subclasses
      of resistance (R) genes, members of which recognize unrelated pathogens. We
      tested the ability of TIR and coiled-coil-class (also known as leucine-zipper
      class) R genes to confer resistance to Pseudomonas syringae pv. tomato or
      Peronospora parasitica in SA-depleted (NahG) and nim1/npr1 plants. We found that
      all of the P. syringae pv. tomato-specific R genes tested were dependent upon SA
      accumulation, while none showed strong dependence upon NIM1/NPR1 activity. A
      similar SA dependence was observed for the P. parasitica TIR and CC-class R genes
      RPP5 and RPP8, respectively. However, the P. parasitica-specific R genes differed
      in their requirement for NIM1/NPR1, with just RPP5 depending upon NIM1/NPR1
      activity for effectiveness. These data are consistent with the hypothesis that at
      least in Arabidopsis, SA accumulation is necessary for the majority of R-gene
      triggered resistance, while the role of NIM1/NPR in race-specific resistance is
      limited to resistance to P. parasitica mediated by TIR-class R genes.

PMID- 12072476
TI  - Assessing probability of ancestry using simple sequence repeat profiles:
      applications to maize hybrids and inbreds.
AB  - Determination of parentage is fundamental to the study of biology and to
      applications such as the identification of pedigrees. Limitations to studies of
      parentage have stemmed from the use of an insufficient number of hypervariable
      loci and mismatches of alleles that can be caused by mutation or by laboratory
      error and that can generate false exclusions. Furthermore, most studies of
      parentage have been limited to comparisons of small numbers of specific parent
      progeny triplets thereby precluding large-scale surveys of candidates where there
      may be no prior knowledge of parentage. We present an algorithm that can
      determine probability of parentage in circumstances where there is no prior
      knowledge of pedigree and that is robust in the face of missing data or mistyped
      data. We present data from 54 maize hybrids and 586 maize inbreds that were
      profiled using 195 SSR loci including simulations of additional levels of missing
      and mistyped data to demonstrate the utility and flexibility of this algorithm.

PMID- 12072477
TI  - Comparative mapping of the barley Ppd-H1 photoperiod response gene region, which
      lies close to a junction between two rice linkage segments.
AB  - Comparative mapping of cereals has shown that chromosomes of barley, wheat, and
      maize can be described in terms of rice "linkage segments." However, little is
      known about marker order in the junctions between linkage blocks or whether this
      will impair comparative analysis of major genes that lie in such regions. We used
      genetic and physical mapping to investigate the relationship between the distal
      part of rice chromosome 7L, which contains the Hd2 heading date gene, and the
      region of barley chromosome 2HS containing the Ppd-H1 photoperiod response gene,
      which lies near the junction between rice 7 and rice 4 linkage segments. RFLP
      markers were mapped in maize to identify regions that might contain Hd2 or Ppd-H1
      orthologs. Rice provided useful markers for the Ppd-H1 region but comparative
      mapping was complicated by loss of colinearity and sequence duplications that
      predated the divergence of rice, maize, and barley. The sequences of cDNA markers
      were used to search for homologs in the Arabidopsis genome. Homologous sequences
      were found for 13 out of 16 markers but they were dispersed in Arabidopsis and
      did not identify any candidate equivalent region. The implications of the results
      for comparative trait mapping in junction regions are discussed.

PMID- 12072478
TI  - Muller's ratchet and the pattern of variation at a neutral locus.
AB  - The levels and patterns of variation at a neutral locus are analyzed in a haploid
      asexual population undergoing accumulation of deleterious mutations due to
      Muller's ratchet. We find that the movement of Muller's ratchet can be associated
      with a considerable reduction in genetic diversity below classical neutral
      expectation. The extent to which variability is reduced is a function of the
      deleterious mutation rate, the fitness effects of the mutations, and the
      population size. Approximate analytical expressions for the expected genetic
      diversity are compared with simulation results under two different models of
      deleterious mutations: a model where all deleterious mutations have equal effects
      and a model where there are two classes of deleterious mutations. We also find
      that Muller's ratchet can produce a considerable distortion in the neutral
      frequency spectrum toward an excess of rare variants.

PMID- 12072480
TI  - A method for estimating the mutation, gene conversion and recombination
      parameters in small multigene families.
AB  - A simple two-locus gene conversion model is considered to investigate the amounts
      of DNA variation and linkage disequilibrium in small multigene families. The
      exact solutions for the expectations and variances of the amounts of variation
      within and between two loci are obtained. It is shown that gene conversion
      increases the amount of variation within each locus and decreases the amount of
      variation between two loci. The expectation and variance of the amount of linkage
      disequilibrium are also obtained. Gene conversion generates positive linkage
      disequilibrium and the degree of linkage disequilibrium decreases as the
      recombination rate is increased. Using the theoretical results, a method for
      estimating the mutation, gene conversion, and recombination parameters is
      developed and applied to the data of the Amy multigene family in Drosophila
      melanogaster. The gene conversion rate is estimated to be approximately 60-165
      times higher than the mutation rate for synonymous sites.

PMID- 12072479
TI  - The effects of multilocus balancing selection on neutral variability.
AB  - We studied the effect of multilocus balancing selection on neutral nucleotide
      variability at linked sites by simulating a model where diallelic polymorphisms
      are maintained at an arbitrary number of selected loci by means of symmetric
      overdominance. Different combinations of alleles define different genetic
      backgrounds that subdivide the population and strongly affect variability.
      Several multilocus fitness regimes with different degrees of epistasis and
      gametic disequilibrium are allowed. Analytical results based on a multilocus
      extension of the structured coalescent predict that the expected linked neutral
      diversity increases exponentially with the number of selected loci and can become
      extremely large. Our simulation results show that although variability increases
      with the number of genetic backgrounds that are maintained in the population, it
      is reduced by random fluctuations in the frequencies of those backgrounds and
      does not reach high levels even in very large populations. We also show that
      previous results on balancing selection in single-locus systems do not extend to
      the multilocus scenario in a straightforward way. Different patterns of linkage
      disequilibrium and of the frequency spectrum of neutral mutations are expected
      under different degrees of epistasis. Interestingly, the power to detect
      balancing selection using deviations from a neutral distribution of allele
      frequencies seems to be diminished under the fitness regime that leads to the
      largest increase of variability over the neutral case. This and other results are
      discussed in the light of data from the Mhc.

PMID- 12072481
TI  - The coalescent in a continuous, finite, linear population.
AB  - In this article we present a model for analyzing patterns of genetic diversity in
      a continuous, finite, linear habitat with restricted gene flow. The distribution
      of coalescent times and locations is derived for a pair of sequences sampled from
      arbitrary locations along the habitat. The results for mean time to coalescence
      are compared to simulated data. As expected, mean time to common ancestry
      increases with the distance separating the two sequences. Additionally, this mean
      time is greater near the center of the habitat than near the ends. In the distant
      past, lineages that have not undergone coalescence are more likely to have been
      at opposite ends of the population range, whereas coalescent events in the
      distant past are biased toward the center. All of these effects are more
      pronounced when gene flow is more limited. The pattern of pairwise nucleotide
      differences predicted by the model is compared to data collected from sardine
      populations. The sardine data are used to illustrate how demographic parameters
      can be estimated using the model.

PMID- 12072482
TI  - Reconstructing the prior probabilities of allelic phylogenies.
AB  - In general when a phylogeny is reconstructed from DNA or protein sequence data,
      it makes use only of the probabilities of obtaining some phylogeny given a
      collection of data. It is also possible to determine the prior probabilities of
      different phylogenies. This information can be of use in analyzing the biological
      causes for the observed divergence of sampled taxa. Unusually "rare" topologies
      for a given data set may be indicative of different biological forces acting. A
      recursive algorithm is presented that calculates the prior probabilities of a
      phylogeny for different allelic samples and for different phylogenies. This
      method is a straightforward extension of Ewens' sample distribution. The
      probability of obtaining each possible sample according to Ewens' distribution is
      further subdivided into each of the possible phylogenetic topologies. These
      probabilities depend not only on the identity of the alleles and on 4N(mu) (four
      times the effective population size times the neutral mutation rate) but also on
      the phylogenetic relationships among the alleles. Illustrations of the algorithm
      are given to demonstrate how different phylogenies are favored under different
      conditions.

PMID- 12072483
TI  - Nonequivalent Loci and the distribution of mutant effects.
AB  - It has been observed repeatedly that the distribution of new mutations of a
      quantitative trait has a kurtosis (a statistical measure of the distribution's
      shape) that is systematically larger than that of a normal distribution. Here we
      suggest that rather than being a property of individual loci that control the
      trait, the enhanced kurtosis is highly likely to be an emergent property that
      arises directly from the loci being mutationally nonequivalent. We present a
      method of incorporating nonequivalent loci into quantitative genetic modeling and
      give an approximate relation between the kurtosis of the mutant distribution and
      the degree of mutational nonequivalence of loci. We go on to ask whether
      incorporating the experimentally observed kurtosis through nonequivalent loci,
      rather than at locus level, affects any biologically important conclusions of
      quantitative genetic modeling. Concentrating on the maintenance of quantitative
      genetic variation by mutation-selection balance, we conclude that typically
      nonequivalent loci yield a genetic variance that is of order 10% smaller than
      that obtained from the previous approaches. For large populations, when the
      kurtosis is large, the genetic variance may be <50% of the result of equivalent
      loci, with Gaussian distributions of mutant effects.

PMID- 12072484
TI  - Application of the false discovery rate to quantitative trait loci interval
      mapping with multiple traits.
AB  - Controlling the false discovery rate (FDR) has been proposed as an alternative to
      controlling the genome-wise error rate (GWER) for detecting quantitative trait
      loci (QTL) in genome scans. The objective here was to implement FDR in the
      context of regression interval mapping for multiple traits. Data on five traits
      from an F2 swine breed cross were used. FDR was implemented using tests at every
      1 cM (FDR1) and using tests with the highest test statistic for each marker
      interval (FDRm). For the latter, a method was developed to predict comparison
      wise error rates. At low error rates, FDR1 behaved erratically; FDRm was more
      stable but gave similar significance thresholds and number of QTL detected. At
      the same error rate, methods to control FDR gave less stringent significance
      thresholds and more QTL detected than methods to control GWER. Although testing
      across traits had limited impact on FDR, single-trait testing was recommended
      because there is no theoretical reason to pool tests across traits for FDR. FDR
      based on FDRm was recommended for QTL detection in interval mapping because it
      provides significance tests that are meaningful, yet not overly stringent, such
      that a more complete picture of QTL is revealed.

PMID- 12072485
TI  - Precision and high-resolution mapping of quantitative trait loci by use of
      recurrent selection, backcross or intercross schemes.
AB  - Dissecting quantitative genetic variation into genes at the molecular level has
      been recognized as the greatest challenge facing geneticists in the twenty-first
      century. Tremendous efforts in the last two decades were invested to map a wide
      spectrum of quantitative genetic variation in nearly all important organisms onto
      their genome regions that may contain genes underlying the variation, but the
      candidate regions predicted so far are too coarse for accurate gene targeting. In
      this article, the recurrent selection and backcross (RSB) schemes were
      investigated theoretically and by simulation for their potential in mapping
      quantitative trait loci (QTL). In the RSB schemes, selection plays the role of
      maintaining the recipient genome in the vicinity of the QTL, which, at the same
      time, are rapidly narrowed down over multiple generations of backcrossing. With a
      high-density linkage map of DNA polymorphisms, the RSB approach has the potential
      of dissecting the complex genetic architecture of quantitative traits and
      enabling the underlying QTL to be mapped with the precision and resolution needed
      for their map-based cloning to be attempted. The factors affecting efficiency of
      the mapping method were investigated, suggesting guidelines under which
      experimental designs of the RSB schemes can be optimized. Comparison was made
      between the RSB schemes and the two popular QTL mapping methods, interval mapping
      and composite interval mapping, and showed that the scenario of genomic
      distribution of QTL that was unlocked by the RSB-based mapping method is
      qualitatively distinguished from those unlocked by the interval mapping-based
      methods.

PMID- 12072486
TI  - On the detection of imprinted quantitative trait loci in experimental crosses of
      outbred species.
AB  - In this article, the quantitative genetic aspects of imprinted genes and
      statistical properties of methods to detect imprinted QTL are studied. Different
      models to detect imprinted QTL and to distinguish between imprinted and Mendelian
      QTL were compared in a simulation study. Mendelian and imprinted QTL were
      simulated in an F2 design and analyzed under Mendelian and imprinting models.
      Mode of expression was evaluated against the H(0) of a Mendelian QTL as well as
      the H(0) of an imprinted QTL. It was shown that imprinted QTL might remain
      undetected when analyzing the genome with Mendelian models only. Compared to
      testing against a Mendelian QTL, using the H(0) of an imprinted QTL gave a higher
      proportion of correctly identified imprinted QTL, but also gave a higher
      proportion of false inference of imprinting for Mendelian QTL. When QTL were
      segregating in the founder lines, spurious detection of imprinting became more
      prominent under both tests, especially for designs with a small number of F1
      sires.

PMID- 12072487
TI  - Characterization of vesicular stomatitis virus recombinants that express and
      incorporate high levels of hepatitis C virus glycoproteins.
AB  - We generated recombinant vesicular stomatitis viruses (VSV) expressing genes
      encoding hybrid proteins consisting of the extracellular domains of hepatitis C
      virus (HCV) glycoproteins fused at different positions to the transmembrane and
      cytoplasmic domains of the VSV G glycoprotein (E1G and E2G). We show that these
      chimeric proteins are transported to the cell surface and incorporated into VSV
      virions efficiently. We also generated VSV recombinants in which the gene
      encoding the VSV G protein was deleted and replaced by one or both of the E1G and
      E2G genes, together with a green fluorescent protein gene. These DeltaG viruses
      incorporated E1G and E2G proteins at levels approximately equivalent to the
      normal level of VSV G itself, or about 1,200 molecules of each protein per
      virion. Given the potency of VSV recombinants as vaccines in other studies, this
      high-level expression and incorporation of HCV proteins into virions could be
      very important for development of an HCV vaccine. Despite the presence of E1G and
      E2G proteins at high levels in the virions, these virions did not infect cell
      lines that have been reported to support at least a low level of HCV infection
      and replication.

PMID- 12072488
TI  - Neutralizing anti-F glycoprotein and anti-substance P antibody treatment
      effectively reduces infection and inflammation associated with respiratory
      syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the most important virus mediating lower
      respiratory tract illness in infants and young children. RSV infection is
      associated with pulmonary inflammation and increased levels of substance P (SP),
      making the airways and leukocytes that express SP receptors susceptible to the
      proinflammatory effects of this peptide. This study examines combining
      neutralizing anti-F glycoprotein and anti-SP antibody treatment of RSV-infected
      BALB/c mice to inhibit RSV replication and inflammation associated with
      infection. BALB/c mice were prophylactically treated with antibody prior to RSV
      infection or were therapeutically treated at day 2 or 6 post-RSV infection.
      Prophylactic or therapeutic treatment with anti-SP antibodies promptly reduced
      pulmonary inflammatory cell infiltration and decreased the number of cells
      expressing proinflammatory cytokines, while anti-F antibody treatment reduced
      virus titers. The results suggest that combined anti-viral and anti-SP antibody
      treatment may be effective in treating RSV disease.

PMID- 12072489
TI  - AIDS vaccination studies using an ex vivo feline immunodeficiency virus model:
      failure to protect and possible enhancement of challenge infection by four cell
      based vaccines prepared with autologous lymphoblasts.
AB  - Immunogenicity and protective activity of four cell-based feline immunodeficiency
      virus (FIV) vaccines prepared with autologous lymphoblasts were investigated. One
      vaccine was composed of FIV-infected cells that were paraformaldehyde fixed at
      the peak of viral expression. The other vaccines were attempts to maximize the
      expression of protective epitopes that might become exposed as a result of virion
      binding to cells and essentially consisted of cells mildly fixed after saturation
      of their surface with adsorbed, internally inactivated FIV particles. The levels
      of FIV-specific lymphoproliferation exhibited by the vaccinees were comparable to
      the ones previously observed in vaccine-protected cats, but antibodies were
      largely directed to cell-derived constituents rather than to truly viral epitopes
      and had very poor FIV-neutralizing activity. Moreover, under one condition of
      testing, some vaccine sera enhanced FIV replication in vitro. As a further limit,
      the vaccines proved inefficient at priming animals for anamnestic immune
      responses. Two months after completion of primary immunization, the animals were
      challenged with a low dose of homologous ex vivo FIV. Collectively, 8 of 20
      vaccinees developed infection versus one of nine animals mock immunized with
      fixed uninfected autologous lymphoblasts. After a boosting and rechallenge with a
      higher virus dose, all remaining animals became infected, thus confirming their
      lack of protection.

PMID- 12072490
TI  - Engineering of adenovirus vectors containing heterologous peptide sequences in
      the C terminus of capsid protein IX.
AB  - The utility of the present generation of adenovirus (Ad) vectors for gene therapy
      applications could be improved by restricting native viral tropism to selected
      cell types. In order to achieve modification of Ad tropism, we proposed to
      exploit a minor component of viral capsid, protein IX (pIX), for genetic
      incorporation of targeting ligands. Based on the proposed structure of pIX, we
      hypothesized that its C terminus could be used as a site for incorporation of
      heterologous peptide sequences. We engineered recombinant Ad vectors containing
      modified pIX carrying a carboxy-terminal Flag epitope along with a heparan
      sulfate binding motif consisting of either eight consecutive lysines or a
      polylysine sequence. Using an anti-Flag antibody, we have shown that modified
      pIXs are incorporated into virions and display Flag-containing C-terminal
      sequences on the capsid surface. In addition, both lysine octapeptide and
      polylysine ligands were accessible for binding to heparin-coated beads. In
      contrast to virus bearing lysine octapeptide, Ad vector displaying a polylysine
      was capable of recognizing cellular heparan sulfate receptors. We have
      demonstrated that incorporation of a polylysine motif into the pIX ectodomain
      results in a significant augmentation of Ad fiber knob-independent infection of
      CAR-deficient cell types. Our data suggest that the pIX ectodomain can serve as
      an alternative to the fiber knob, penton base, and hexon proteins for
      incorporation of targeting ligands for the purpose of Ad tropism modification.

PMID- 12072491
TI  - Kinetic analysis of the role of intersubunit interactions in human
      immunodeficiency virus type 1 capsid protein assembly in vitro.
AB  - The human immunodeficiency virus type 1 (HIV-1) capsid protein (CA) plays a
      crucial role in both assembly and maturation of the virion. Numerous recent
      studies have focused on either the soluble form of CA or the polymer end product
      of in vitro CA assembly. The CA polymer, in particular, has been used to study CA
      CA interactions because it is a good model for the CA interactions within the
      virion core. However, analysis of the process of in vitro CA assembly can yield
      valuable insights into CA-CA interactions and the mechanism of core assembly. We
      describe here a method for the analysis of CA assembly kinetics wherein the
      progress of assembly is monitored by using turbidity. At pH 7.0 the addition of
      either of the isolated CA domains (i.e., the N or the C domain) to an assembly
      reaction caused a decrease in the assembly rate by competing for binding to the
      full-length CA protein. At pH 8.0 the addition of the isolated C domain had a
      similar inhibitory affect on CA assembly. However, at pH 8.0 the isolated N
      domain had no affect on the rate of CA assembly but, when mixed with the C
      domain, it alleviated the C-domain inhibition. These data provide biochemical
      evidence for a pH-sensitive homotypic N-domain interaction, as well as for an N-
      and C-domain interaction.

PMID- 12072492
TI  - Heparin binds to murine leukemia virus and inhibits Env-independent attachment
      and infection.
AB  - Certain glycosaminoglycans (GAGs), including heparin, inhibit infection by murine
      leukemia virus (MLV). We now show that this is due to inhibition of virus
      attachment independent of the interaction between viral envelope proteins (Env)
      and their cellular receptors. Heparin blocked the binding of both Env-deficient
      and amphotropic MLV (MLV-A) particles to NIH 3T3 fibroblasts, CHO cells which
      lack the amphotropic retroviral receptor Pit-2, and CHO cells transfected with
      Pit-2 (CHO-Pit-2). Heparin also inhibited the transduction of NIH 3T3 cells by
      MLV-A over a similar concentration range. This effect was observed within 15 min
      of exposure to retrovirus. Preloading target cells with heparin had no effect on
      transduction and both MLV-A and Env-deficient retrovirus bound efficiently to
      heparin-coated agarose beads, suggesting that heparin interacts with the virus
      rather than the target cell. This requires both a strong negative charge and a
      specific structure since GAGs with different charge and carbohydrate composition
      inhibited virus infection variably. The specificity of GAG-virus interaction also
      depends on the producer cells, since virus packaged by murine GP+EnvAM12 cells
      was 1,000-fold more sensitive to inhibition by chondroitin sulfate A than was
      virus packaged by human FLYA13 packaging cells. No evidence for an interaction
      between MLV and cell surface proteoglycans was found, however, since the
      attachment of MLV-A and envelope-defective virus to proteoglycan-deficient
      CHOpgsA-745 cells was similar to that seen with both wild-type and CHO-Pit-2
      cells. Although the molecular mechanism is unclear, this study presents evidence
      that Env receptor-independent attachment is an important step in MLV infection.

PMID- 12072493
TI  - Characterization of low- and very-low-density hepatitis C virus RNA-containing
      particles.
AB  - The presence of hepatitis C virus (HCV) RNA-containing particles in the low
      density fractions of plasma has been associated with high infectivity. However,
      the nature of circulating HCV particles and their association with
      immunoglobulins or lipoproteins as well as the characterization of cell entry
      have all been subject to conflicting reports. For a better analysis of HCV RNA
      containing particles, we quantified HCV RNA in the low-density fractions of
      plasma corresponding to the very-low-density lipoprotein (VLDL), intermediate
      density lipoprotein, and low-density lipoprotein (LDL) fractions from untreated
      chronically HCV-infected patients. HCV RNA was always found in at least one of
      these fractions and represented 8 to 95% of the total plasma HCV RNA.
      Surprisingly, immunoglobulins G and M were also found in the low-density
      fractions and could be used to purify the HCV RNA-containing particles (lipo-viro
      particles [LVP]). Purified LVP were rich in triglycerides; contained at least
      apolipoprotein B, HCV RNA, and core protein; and appeared as large spherical
      particles with a diameter of more than 100 nm and with internal structures.
      Delipidation of these particles resulted in capsid-like structures recognized by
      anti-HCV core protein antibody. Purified LVP efficiently bind and enter
      hepatocyte cell lines, while serum or whole-density fractions do not. Binding of
      these particles was competed out by VLDL and LDL from noninfected donors and was
      blocked by anti-apolipoprotein B and E antibodies, whereas upregulation of the
      LDL receptor increased their internalization. These results suggest that the
      infectivity of LVP is mediated by endogenous proteins rather than by viral
      components providing a mechanism of escape from the humoral immune response.

PMID- 12072495
TI  - Template requirements for de novo RNA synthesis by hepatitis C virus
      nonstructural protein 5B polymerase on the viral X RNA.
AB  - The hepatitis C virus (HCV)-encoded NS5B protein is an RNA-dependent RNA
      polymerase which plays a substantial role in viral replication. We expressed and
      purified the recombinant NS5B of an HCV genotype 3a from Esherichia coli, and we
      investigated its ability to bind to the viral RNA and its enzymatic activity. The
      results presented here demonstrate that NS5B interacts strongly with the coding
      region of positive-strand RNA, although not in a sequence-specific manner. It was
      also determined that more than two molecules of polymerase bound sequentially to
      this region with the direction 3' to 5'. Also, we attempted to determine the
      initiation site(s) of de novo synthesis by NS5B on X RNA, which contains the last
      98 nucleotides of HCV positive-strand RNA. The initiation site(s) on X RNA was
      localized in the pyrimidine-rich region of stem I. However, when more than five
      of the nucleotides of stem I in X RNA were deleted from the 3' end, RNA synthesis
      initiated at another site of the specific ribonucleotide. Our study also showed
      that the efficiency of RNA synthesis, which was directed by X RNA, was maximized
      by the GC base pair at the penultimate position from the 3' end of the stem.
      These results will provide some clues to understanding the mechanism of HCV
      genomic RNA replication in terms of viral RNA-NS5B interaction and the initiation
      of de novo RNA synthesis.

PMID- 12072496
TI  - Species-specific receptor recognition by a minor-group human rhinovirus (HRV):
      HRV serotype 1A distinguishes between the murine and the human low-density
      lipoprotein receptor.
AB  - Human rhinoviruses (HRV) of the minor receptor group use several members of the
      low-density lipoprotein receptor superfamily for cell entry. These proteins are
      evolutionarily highly conserved throughout species and are almost ubiquitously
      expressed. Their common building blocks, cysteine-rich ligand binding repeats
      about 40 amino acids in length, exhibit considerable sequence similarity. Various
      numbers of these repeats are present in the different receptors. We here
      demonstrate that HRV type 1A (HRV1A) replicates in mouse cells without
      adaptation. Furthermore, although closely related to HRV2, it fails to bind to
      the human low-density lipoprotein receptor but recognizes the murine protein,
      whereas HRV2 binds equally well to both homologues. This difference went
      unnoticed due to the presence of other receptors, such as the low-density
      lipoprotein receptor-related protein, which allow species-independent attachment.
      The species specificity of HRV1A reported here will aid in defining amino acid
      residues establishing the contact between the viral surface and the receptor.

PMID- 12072494
TI  - Impact of cytokines on replication in the thymus of primary human
      immunodeficiency virus type 1 isolates from infants.
AB  - Early infection of the thymus with the human immunodeficiency virus (HIV) may
      explain the more rapid disease progression among children infected in utero than
      in children infected intrapartum. Therefore, we analyzed infection of thymocytes
      in vitro by HIV type 1 primary isolates, obtained at or near birth, from 10
      children with different disease outcomes. HIV isolates able to replicate in the
      thymus and impact thymopoiesis were present in all infants, regardless of the
      timing of viral transmission and the rate of disease progression. Isolates from
      newborns utilized CCR5, CXCR4, or both chemokine receptors to enter thymocytes.
      Viral expression was observed in discrete thymocyte subsets postinfection with
      HIV isolates using CXCR4 (X4) and isolates using CCR5 (R5), despite the wider
      distribution of CXCR4 in the thymus. In contrast to previous findings, the X4
      primary isolates were not more cytopathic for thymocytes than were the R5
      isolates. The cytokines interleukin-2 (IL-2), IL-4, and IL-7 increased HIV
      replication in the thymus by inducing differentiation and expansion of mature
      CD27(+) thymocytes expressing CXCR4 or CCR5. IL-2 and IL-4 together increased
      expression of CXCR4 and CCR5 in this population, whereas IL-4 and IL-7 increased
      CXCR4 but not CCR5 expression. IL-2 plus IL-4 increased the viral production of
      all pediatric isolates, but IL-4 and IL-7 had a significantly higher impact on
      the replication of X4 isolates compared to R5 isolates. Our studies suggest that
      coreceptor use by HIV primary isolates is important but is not the sole
      determinant of HIV pathogenesis in the thymus.

PMID- 12072498
TI  - Cell surface major histocompatibility complex class II proteins are regulated by
      the products of the gamma(1)34.5 and U(L)41 genes of herpes simplex virus 1.
AB  - Modulation of host immune responses has emerged as a common strategy employed by
      herpesviruses both to establish life-long infections and to affect recovery from
      infection. Herpes simplex virus 1 (HSV-1) blocks the major histocompatibility
      complex (MHC) class I antigen presentation pathway by inhibiting peptide
      transport into the endoplasmic reticulum. The interaction of viral gene products
      with the MHC class II pathway, however, has not been thoroughly investigated,
      although CD4(+) T cells play an important role in human recovery from infection.
      We have investigated the stability, distribution, and state of MHC class II
      proteins in glioblastoma cells infected with wild-type HSV-1 or mutants lacking
      specific genes. We report the following findings. (i) Wild-type virus infection
      caused a decrease in the accumulation of class II protein on the surface of cells
      and a decrease in the endocytosis of lucifer yellow or dextran conjugated to
      fluorescein isothiocyanate but no decrease in the total amount of MHC class II
      proteins relative to the levels seen in mock-infected cells. (ii) Although the
      total amount of MHC class II protein remained unchanged, the amounts of cell
      surface MHC class II proteins were higher in cells infected with the U(L)41
      negative mutant, which lacks the virion host shutoff protein, and especially high
      in cells infected with the gamma(1)34.5-negative mutant. We conclude that
      infected cells attempt to respond to infection by increased acquisition of
      antigens and transport of MHC class II proteins to the cell surface and that
      these responses are blocked in part by the virion host shutoff protein encoded by
      the U(L)41 gene and in large measure by the direct or indirect action of the
      infected cell protein 34.5, the product of the gamma(1)34.5 gene.

PMID- 12072497
TI  - Coreceptor phenotype of natural human immunodeficiency virus with nef deleted
      evolves in vivo, leading to increased virulence.
AB  - The Sydney Blood Bank Cohort is a group of patients with slowly progressive
      infection by a human immunodeficiency virus strain containing spontaneous
      deletions within the nef long terminal repeat region. In 1999, 18 years after the
      initial infection, one of the members (D36) developed AIDS. In this work, we used
      an ex vivo human lymphoid cell culture system to analyze two viral isolates
      obtained from this patient, one prior to the onset of AIDS in 1995 and one after
      disease progression in 1999. Both D36 isolates were less potent in depleting
      CD4(+) T cells than a reference dualtropic, nef-bearing viral isolate. However,
      the 1999 isolate was measurably more cytotoxic to CD4(+) T cells than the 1995
      isolate. Interestingly, although both isolates were nearly equally potent in
      depleting CCR5(+) CD4(+) T cells, the cytotoxic effect of the 1999 isolate toward
      CCR5(-) CD4(+) T cells was significantly higher. Furthermore, GHOST cell
      infection assays and blocking experiments with the CXCR4 inhibitor AMD3100 showed
      that the later D36 1999 isolate could infect both CCR5(+) and CCR5(-) CXCR4(+)
      cells efficiently, while infection by the 1995 isolate was nearly completely
      restricted to CCR5(+) cells. Sequence analysis of the V1/V2 and V3 regions of the
      viral envelope protein gp120 revealed that the more efficient CXCR4 usage of the
      later isolate might be caused by an additional potential N-glycosylation site in
      the V1/V2 loop. In conclusion, these data show that an in vivo evolution of the
      tropism of this nef-deleted strain toward an X4 phenotype was associated with a
      higher cytopathic potential and progression to AIDS.

PMID- 12072499
TI  - Characterization of human immunodeficiency virus type 1 (HIV-1) Gag- and Gag
      peptide-specific CD4(+) T-cell clones from an HIV-1-seronegative donor following
      in vitro immunization.
AB  - Substantial evidence argues that human immunodeficiency virus type 1 (HIV-1)
      specific CD4(+) T cells play an important role in the control of HIV-1
      replication in infected individuals. Moreover, it is increasingly clear that an
      HIV vaccine should elicit potent cytotoxic lymphocyte and antibody responses that
      will likely require an efficient CD4(+) T-cell response. Therefore, understanding
      and characterizing HIV-specific CD4(+) T-cell responses is an important aim. Here
      we describe the generation of HIV-1 Gag- and Gag peptide-specific CD4(+) T-cell
      clones from an HIV-1-seronegative donor by in vitro immunization with HIV-1 Gag
      peptides. The Gag peptides were able to induce a strong CD4(+) T-cell immune
      response in peripheral blood mononuclear cells from the HIV-1-seronegative donor.
      Six Gag peptide-specific CD4(+) T-cell clones were isolated and their epitopes
      were mapped. The region of p24 between amino acids 201 and 300 of Gag was defined
      as the immunodominant region of Gag. A new T helper epitope in the p6 protein of
      Gag was identified. Two clones were shown to recognize Gag peptides and processed
      Gag protein, while the other four clones reacted only to Gag peptides under the
      experimental conditions used. Functional analysis of the clones indicated that
      both Th1 and Th2 types of CD4(+) T cells were obtained. One clone showed direct
      antigen-specific cytotoxic activity. These clones represent a valuable tool for
      understanding the cellular immune response to HIV-1, and the study provides new
      insights into the HIV-1-specific CD4(+) T-cell response and the induction of an
      anti-Gag and -Gag peptide cellular primary immune response in vitro.

PMID- 12072501
TI  - Correlation of major histocompatibility complex class I downregulation with
      resistance of human T-cell leukemia virus type 1-infected T cells to cytotoxic T
      lymphocyte killing in a rat model.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) in
      infected individuals after a long incubation period. Despite the apparent
      transforming ability of HTLV-1 under experimental conditions, most HTLV-1
      carriers are asymptomatic. These facts suggest that HTLV-1 is controlled by host
      immunity in most carriers. To understand the interplay between host immunity and
      HTLV-1-infected cells, in this study, we isolated several HTLV-1 Tax-specific
      cytotoxic T-lymphocyte (CTL) lines from rats inoculated with Tax-coding DNA and
      investigated the long-term effects of the CTL on syngeneic HTLV-1-infected T
      cells. Our results demonstrated that long-term mixed culture of these CTL and the
      virus-infected T cells led to the emergence of CTL-resistant HTLV-1-infected
      cells. Although the Tax expression level in these resistant cells was equivalent
      to that in the parental cells, expression of surface major histocompatibility
      complex class I (MHC-I) was significantly downregulated in the resistant cells.
      Downregulation of MHC-I was more apparent in RT1.A(l), which presents a Tax
      epitope recognized by the CTL established in this study. Moreover, peptide
      pulsing resulted in killing of the resistant cells by CTL, indicating that
      resistance was caused by a decreased epitope density on the infected cell
      surface. This may be one of the mechanisms for persistence of HTLV-1-infected
      cells that evade CTL lysis and potentially develop ATL.

PMID- 12072502
TI  - Herpes simplex virus type 1 origins of DNA replication play no role in the
      regulation of flanking promoters.
AB  - Herpes simplex virus (HSV) exhibits altered gene regulation in neuronal compared
      to nonneuronal tissues. It has been hypothesized that initiation of DNA synthesis
      at the viral origins of replication (oriS and oriL) is a critical step in the
      upregulation of transcriptional activity of flanking divergent promoters, thereby
      increasing productive gene expression in neurons. Notably, oriS is flanked by the
      immediate-early (IE) ICP4 and ICP22/47 promoters, and oriL is flanked by the
      early (E) UL29 and UL30 promoters. To test this hypothesis further, a series of
      constructs were generated in which these promoters were placed upstream of
      luciferase genes. In addition, DNA replication origins were deleted in the
      context of these promoter constructs. All cassettes were recombined into the
      viral genome of HSV type 1 strain KOS at a site distal to its native origins.
      Recombinant reporter expression was monitored in vitro and in vivo to determine
      the role of viral origins of DNA replication in the regulation of their flanking
      promoters. Reporter gene expression was unaffected by the presence or absence of
      oriS or oriL, with the exception of a twofold increase in ICP22/47 promoter
      activity in the absence of oriS. DNA synthesis inhibitors resulted in a decrease
      of both IE- and E-promoter activity in primary cells but not continuous cell
      cultures. Reporter activity was readily assayed in vivo during acute infection
      and reactivation from latency and was also sensitive to DNA synthesis inhibitors.
      In all assays, reporter gene expression was unaffected by the presence or absence
      of either oriS or oriL. These data support the requirement of DNA synthesis for
      full viral gene expression in vivo but suggest that the origin elements play no
      role in the regulation of their flanking promoters.

PMID- 12072500
TI  - Origin of human immunodeficiency virus type 1 quasispecies emerging after
      antiretroviral treatment interruption in patients with therapeutic failure.
AB  - The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus
      type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants
      are usually replaced by drug-sensitive ones when the selective pressure of the
      drugs is removed, as the former have reduced fitness in a drug-free environment.
      This was the rationale for the design of structured ARV treatment interruption
      (STI) studies for the management of HIV-1 patients with treatment failure. We
      have studied the origin of drug-sensitive HIV-1 quasispecies emerging after STI
      in patients with treatment failure due to ARV drug resistance. Plasma and
      peripheral blood mononuclear cell samples were obtained the day of treatment
      interruption (day 0) and 30 and 60 days afterwards. HIV-1 pol and env were
      partially amplified, cloned, and sequenced. At day 60 drug-resistant variants
      were replaced by completely or partially sensitive quasispecies. Phylogenetic
      analyses of pol revealed that drug-sensitive variants emerging after STI were not
      related to their immediate temporal ancestors but formed a separate cluster,
      demonstrating that STI leads to the recrudescence and reemergence of a
      sequestrated viral population rather than leading to the back mutation of drug
      resistant forms. No evidence for concomitant changes in viral tropism was seen,
      as deduced from env sequences. This study demonstrates the important role that
      the reemergence of quasispecies plays in HIV-1 population dynamics and points out
      the difficulties that may be found when recycling ARV therapies with patients
      with treatment failure.

PMID- 12072504
TI  - Translational regulation of human papillomavirus type 16 E7 mRNA by the peptide
      SEQIKA, shared by rabbit alpha(1)-globin and human cytokeratin 7.
AB  - The possible biochemical factors able to affect the in vitro expression of the
      high-risk human papillomavirus type 16 (HPV16) E7 oncoprotein have been analyzed.
      Evidence is provided that E7 mRNA stability is increased and, conversely,
      transcript translation is inhibited by binding to a 32-kDa protein from rabbit
      reticulocyte lysate; sequence analysis identified the 32-kDa binding protein as
      rabbit alpha(1)-globin protein; and interaction between rabbit alpha(1)-globin
      and E7 mRNA occurs through the 6-mer peptide SEQIKA present in human cytokeratin
      7 protein. The in vitro data were confirmed by the occurrence of HPV16 E7 mRNA
      cytokeratin 7 binding in squamous cervical cancer SiHa cells.

PMID- 12072503
TI  - Selection of 3'-template bases and initiating nucleotides by hepatitis C virus
      NS5B RNA-dependent RNA polymerase.
AB  - De novo RNA synthesis by hepatitis C virus (HCV) nonstructural protein 5B (NS5B)
      RNA-dependent RNA polymerase has been investigated using short RNA templates.
      Various templates including those derived from the HCV genome were evaluated by
      examining the early steps of de novo RNA synthesis. NS5B was shown to be able to
      produce an initiation dinucleotide product from templates as short as 4-mer and
      from the 3'-terminal sequences of both plus and minus strands of the HCV RNA
      genome. GMP, GDP, and guanosine were able to act as an initiating nucleotide in
      de novo RNA synthesis, indicating that the triphosphate moiety is not absolutely
      required by an initiating nucleotide. Significant amounts of the initiation
      product accumulated in de novo synthesis, and elongation from the dinucleotide
      was observed when large amounts of dinucleotide were available. This result
      suggests that NS5B, a template, and incoming nucleotides are able to form an
      initiation complex that aborts frequently by releasing the dinucleotide product
      before transition to an elongation complex. The transition is rate limiting.
      Furthermore, we discovered that the secondary structure of a template was not
      essential for de novo initiation and that 3'-terminal bases of a template
      conferred specificity in selection of an initiation site. Initiation can occur at
      the +1, +2, or +3 position numbered from the 3' end of a template depending on
      base composition. Pyrimidine bases at any of the three positions are able to
      serve as an initiation site, while purine bases at the +2 and +3 positions do not
      support initiation. This result implies that HCV possesses an intrinsic ability
      to ensure that de novo synthesis is initiated from the +1 position and to
      maintain the integrity of the 3' end of its genome. This assay system should be
      an important tool for investigating the detailed mechanism of de novo initiation
      by HCV NS5B as well as other viral RNA polymerases.

PMID- 12072506
TI  - Processing map and essential cleavage sites of the nonstructural polyprotein
      encoded by ORF1 of the feline calicivirus genome.
AB  - Feline calicivirus (FCV) nonstructural proteins are translated as part of a large
      polyprotein that undergoes autocatalytic processing by the virus-encoded 3C-like
      proteinase. In this study, we mapped three new cleavage sites (E(46)/A(47),
      E(331)/D(332), and E(685)/N(686)) recognized by the virus proteinase in the N
      terminal part of the open reading frame 1 (ORF1) polyprotein to complete the
      processing map. Taken together with two sites we identified previously
      (E(960)/A(961) and E(1071)/S(1072)), the FCV ORF1 polyprotein contains five
      cleavage sites that define the borders of six proteins with calculated molecular
      masses of 5.6, 32, 38.9, 30.1, 12.7, and 75.7 kDa, which we designated p5.6, p32,
      p39 (NTPase), p30, p13 (VPg), and p76 (Pro-Pol), respectively. Mutagenesis of the
      E to A in each of these cleavage sites in an infectious FCV cDNA clone was lethal
      for the virus, indicating that these cleavages are essential in a productive
      virus infection. Mutagenesis of two cleavage sites (E(1345)/T(1346) and
      E(1419)/G(1420)) within the 75.7-kDa Pro-Pol protein previously mapped in
      bacterial expression studies was not lethal.

PMID- 12072505
TI  - Complementary roles of multiple nuclear targeting signals in the capsid proteins
      of the parvovirus minute virus of mice during assembly and onset of infection.
AB  - This report describes the distribution of conventional nuclear localization
      sequences (NLS) and of a beta-stranded so-called nuclear localization motif (NLM)
      in the two proteins (VP1, 82 kDa; VP2, 63 kDa) forming the T=1 icosahedral capsid
      of the parvovirus minute virus of mice (MVM) and their functions in viral
      biogenesis and the onset of infection. The approximately 10 VP1 molecules
      assembled in the MVM particle harbor in its 142-amino-acid (aa) N-terminal
      specific region four clusters of basic amino acids, here called BC1 (aa 6 to 10),
      BC2 (aa 87 to 90), BC3 (aa 109 to 115), and BC4 (aa 126 to 130), that fit
      consensus NLS and an NLM placed toward the opposite end of the polypeptide (aa
      670 to 680) found to be necessary for VP2 nuclear uptake. Deletions and site
      directed mutations constructed in an infectious MVM plasmid showed that BC1, BC2,
      and NLM are cooperative nuclear transport sequences in singly expressed VP1
      subunits and that they conferred nuclear targeting competence on the VP1/VP2
      oligomers arising in normal infection, while BC3 and BC4 did not display nuclear
      transport activity. Notably, VP1 proteins mutated at BC1 and -2, and particularly
      with BC1 to -4 sequences deleted, induced nuclear and cytoplasmic foci of
      colocalizing conjugated ubiquitin that could be rescued from the ubiquitin
      proteasome degradation pathway by the coexpression of VP2 and NS2 isoforms. These
      results suggest a role for VP2 in viral morphogenesis by assisting cytoplasmic
      folding of VP1/VP2 subviral complexes, which is further supported by the capacity
      of NLM-bearing transport-competent VP2 subunits to recruit VP1 into the nuclear
      capsid assembly pathway regardless of the BC composition. Instead, all four BC
      sequences, which are located in the interior of the capsid, were absolutely
      required by the incoming infectious MVM particle for the onset of infection,
      suggesting either an important conformational change or a disassembly of the coat
      for nuclear entry of a VP1-associated viral genome. Therefore, the evolutionarily
      conserved BC sequences and NLM domains provide complementary nuclear transport
      functions to distinct supramolecular complexes of capsid proteins during the
      autonomous parvovirus life cycle.

PMID- 12072507
TI  - Activity of polymerase proteins of vaccine and wild-type measles virus strains in
      a minigenome replication assay.
AB  - The relative activities of five measles virus (MV) polymerase (L) proteins were
      compared in an intracellular, plasmid-based replication assay. When coexpressed
      with N and P proteins from an attenuated strain, L proteins from two attenuated
      viruses directed the production of up to eight times more reporter protein from
      an MV minigenome than the three wild-type L proteins. Northern blot analysis
      demonstrated that the differences in reporter protein production correlated with
      mRNA transcription levels. Increased activity of polymerases from attenuated
      viruses equally affected mRNA transcription and minigenome replication. The
      higher level of transcription may be a consequence of increased template
      availability or may be an independent effect of the elevated activity of the
      attenuated polymerases. Coexpression of wild-type L proteins with homologous N
      and P proteins did not affect the activity of the wild-type polymerases,
      indicating that the differential activity was a function of the L proteins alone.
      Use of a minigenome that incorporated two nucleotide changes found in the genomic
      leader of the three wild-type viruses did not raise the activity of the wild-type
      L proteins. These data demonstrate that increased polymerase activity
      differentiates attenuated from wild-type viruses and suggest that functions
      involved in RNA synthesis contribute to the attenuated phenotype of MV vaccine
      strains.

PMID- 12072508
TI  - Analysis of a temperature-sensitive mutant rotavirus indicates that NSP2 octamers
      are the functional form of the protein.
AB  - Evidence that NSP2 plays a role in packaging and replication comes from studies
      on tsE(1400), a rotavirus mutant with a temperature-sensitive (ts) lesion in the
      NSP2 gene. Cells infected with tsE and maintained at nonpermissive temperature
      contain few replication-assembly factories (viroplasms) or replication
      intermediates and produce virus particles that are mostly empty. Sequence
      analysis has indicated that an A152V mutation in NSP2 is responsible for the ts
      phenotype of tsE. To gain insight into the effect of the mutation on the
      octameric structure and biochemical activities of tsE NSP2, the protein was
      expressed in bacteria and purified to homogeneity. Analytical ultracentrifugation
      showed that tsE NSP2 formed octamers which, like those formed by wild-type (wt)
      NSP2, undergo conformational change into more compact structures upon binding of
      nucleotides. However, exposure to Mg(2+) and the nonpermissive temperature caused
      disruption of the tsE octamers and yielded the formation of polydisperse NSP2
      aggregates, events not observed with wt octamers. Biochemical analysis showed
      that the RNA-binding, helix-destabilizing and NTPase activities of tsE NSP2 were
      significantly less at the nonpermissive temperature than at the permissive
      temperature. In contrast, these activities for wt NSP2 were higher at the
      nonpermissive temperature. Our results indicate that the octamer is the fully
      functional form of NSP2 and the form required for productive virus replication.
      The propensity of tsE NSP2 to form large aggregates provides a possible
      explanation for the inability of the protein to support packaging and/or
      replication in the infected cell at the nonpermissive temperature.

PMID- 12072510
TI  - The RNA polymerase of influenza a virus is stabilized by interaction with its
      viral RNA promoter.
AB  - The RNA polymerase of the influenza virus is responsible for the transcription
      and replication of the segmented RNA viral genome during infection of host cells.
      Polymerase function is known to be strictly dependent on interaction with its RNA
      promoter, but no attempts to investigate whether the virion RNA (vRNA) promoter
      stabilizes the polymerase have been reported previously. Here we tested whether
      the vRNA promoter protects the polymerase against heat inactivation. We prepared
      partially purified recombinant influenza A virus RNA polymerase, in the absence
      of influenza virus vRNA promoter sequences, by transient transfection of
      expression plasmids into human kidney 293T cells. The polymerase was found to be
      heat labile at 40 degrees C in the absence of added vRNA. However, it was
      protected from heat inactivation if both the 5' and 3' strands of the vRNA
      promoter were present. By using the ability of vRNA to protect the enzyme against
      heat inactivation, we established a novel assay, in conjunction with a mutagenic
      approach, that was used to test the secondary structure requirement of the vRNA
      promoter for polymerase binding. Binding required a panhandle structure and the
      presence of local hairpin loop structures in both the 5' and 3' ends of vRNA, as
      suggested by the corkscrew model. The interaction of the vRNA promoter with the
      influenza virus RNA polymerase heterotrimeric complex is likely to favor a
      particular closed conformation of the complex, thereby ensuring the stability of
      the RNA polymerase within both the infected cell and the isolated virus.

PMID- 12072509
TI  - Novel endogenous retrovirus in rabbits previously reported as human retrovirus 5.
AB  - Human retrovirus 5 (HRV-5) represented a fragment of a novel retrovirus sequence
      identified in human RNA and DNA preparations. In this study, the genome of HRV-5
      was cloned and sequenced and integration sites were analyzed. Using PCR and
      Southern hybridization, we showed that HRV-5 is not integrated into human DNA. A
      survey of other species revealed that HRV-5 is present in the genomic DNA of the
      European rabbit (Oryctolagus cuniculus) and belongs to an endogenous retrovirus
      family found in rabbits. The presence of rabbit sequences flanking HRV-5
      proviruses in human DNA extracts suggested that rabbit DNA was present in our
      human extracts, and this was confirmed by PCR analysis that revealed the presence
      of rabbit mitochondrial DNA sequences in four of five human DNA preparations
      tested. The origin of the rabbit DNA and HRV-5 in human DNA preparations remains
      unclear, but laboratory contamination cannot explain the preferential detection
      of HRV-5 in inflammatory diseases and lymphomas reported previously. This is the
      first description of a retrovirus genome in rabbits, and sequence analysis shows
      that it is related to but distinct from A-type retroelements of mice and other
      rodents. The species distribution of HRV-5 is restricted to rabbits; other
      species, including other members of the order Lagomorpha, do not contain this
      sequence. Analysis of HRV-5 expression by Northern hybridization and reverse
      transcriptase PCR indicates that the virus is transcribed at a low level in many
      rabbit tissues. In light of these findings we propose that the sequence
      previously designated HRV-5 should now be denoted RERV-H (for rabbit endogenous
      retrovirus H).

PMID- 12072511
TI  - The amino-terminal half of Sendai virus C protein is not responsible for either
      counteracting the antiviral action of interferons or down-regulating viral RNA
      synthesis.
AB  - The Sendai virus C proteins, C', C, Y1, and Y2, are a nested set of independently
      initiated carboxy-coterminal proteins translated from a reading frame overlapping
      the P frame on the P mRNA. The C proteins are extremely versatile and have been
      shown to counteract the antiviral action of interferons (IFNs), to down-regulate
      viral RNA synthesis, and to promote virus assembly. Using the stable cell lines
      expressing the C, Y1, Y2, or truncated C protein, we investigated the region
      responsible for anti-IFN action and for down-regulating viral RNA synthesis.
      Truncation from the amino terminus to the middle of the C protein maintained the
      inhibition of the signal transduction of IFNs, the formation of IFN-stimulated
      gene factor 3 (ISGF3) complex, the generation of the anti-vesicular stomatitis
      virus state, and the synthesis of viral RNA, but further truncation resulted in
      the simultaneous loss of all of these inhibitory activities. A relatively small
      truncation from the carboxy terminus also abolished all of these inhibitory
      activities. These data indicated that the activities of the C protein to
      counteract the antiviral action of IFNs and to down-regulate viral RNA synthesis
      were not encoded within a region of at least 98 amino acids in its amino-terminal
      half.

PMID- 12072512
TI  - Immune control of the number and reactivation phenotype of cells latently
      infected with a gammaherpesvirus.
AB  - Despite active immune responses, gammaherpesviruses establish latency. In a
      related process, these viruses also persistently replicate by using a mechanism
      that requires different viral genes than acute-phase replication. Many questions
      remain about the role of immunity in chronic gammaherpesvirus infection,
      including whether the immune system controls latency by regulating latent cell
      numbers and/or other properties and what specific immune mediators control
      latency and persistent replication. We show here that CD8(+) T cells regulate
      both latency and persistent replication and demonstrate for the first time that
      CD8(+) T cells regulate both the number of latently infected cells and the
      efficiency with which infected cells reactivate from latency. Furthermore, we
      show that gamma interferon (IFN-gamma) and perforin, which play no significant
      role during acute infection, are essential for immune control of latency and
      persistent replication. Surprisingly, the effects of perforin and IFN-gamma are
      site specific, with IFN-gamma being important in peritoneal cells while perforin
      is important in the spleen. Studies of the mechanisms of action of IFN-gamma and
      perforin revealed that perforin acts primarily by controlling the number of
      latently infected cells while IFN-gamma acts primarily by controlling
      reactivation efficiency. The immune system therefore controls chronic
      gammaherpesvirus infection by site-specific mechanisms that regulate both the
      number and reactivation phenotype of latently infected cells.

PMID- 12072513
TI  - Evidence for segment-nonspecific packaging of the influenza a virus genome.
AB  - The influenza A virus genome is composed of eight negative-sense RNA segments
      (called vRNAs), all of which must be packaged to produce an infectious virion. It
      is not clear whether individual vRNAs are packaged specifically or at random,
      however, and the total vRNA capacity of the virion is unknown. We have created
      modified forms of the viral nucleoprotein (NP), neuraminidase (NA), and
      nonstructural (NS) vRNAs that encode green or yellow fluorescent proteins and
      studied the efficiency with which these are packaged by using a plasmid-based
      influenza A virus assembly system. Packaging was assessed precisely and
      quantitatively by scoring transduction of the fluorescent markers in a single
      round infectivity assay with a flow cytometer. We found that, under conditions in
      which virions are limiting, pairs of alternatively tagged vRNAs compete for
      packaging but do so in a nonspecific manner. Reporters representing different
      vRNAs were not packaged additively, as would be expected under specific
      packaging, but instead appeared to compete for a common niche in the virion.
      Moreover, 3 to 5% of transduction-competent viruses were found to incorporate two
      alternative reporters, regardless of whether those reporters represented the same
      or different vRNAs - a finding compatible with random, but not with specific,
      packaging. Probabilistic estimates suggest that in order to achieve this level of
      dual transduction by chance alone, each influenza A virus virion must package an
      average of 9 to 11 vRNAs.

PMID- 12072514
TI  - The lipopolysaccharide and beta-1,3-glucan binding protein gene is upregulated in
      white spot virus-infected shrimp (Penaeus stylirostris).
AB  - Pattern recognition proteins such as lipopolysaccharide and beta-1,3-glucan
      binding protein (LGBP) play an important role in the innate immune response of
      crustaceans and insects. Random sequencing of cDNA clones from a hepatopancreas
      cDNA library of white spot virus (WSV)-infected shrimp provided a partial cDNA
      (PsEST-289) that showed similarity to the LGBP gene of crayfish and insects.
      Subsequently full-length cDNA was cloned by the 5'-RACE (rapid amplification of
      cDNA ends) technique and sequenced. The shrimp LGBP gene is 1,352 bases in length
      and is capable of encoding a polypeptide of 376 amino acids that showed
      significant similarity to homologous genes from crayfish, insects, earthworms,
      and sea urchins. Analysis of the shrimp LGBP deduced amino acid sequence
      identified conserved features of this gene family including a potential
      recognition motif for beta-(1-->3) linkage of polysaccharides and putative RGD
      cell adhesion sites. It is known that LGBP gene expression is upregulated in
      bacterial and fungal infection and that the binding of lipopolysaccharide and
      beta-1,3-glucan to LGBP activates the prophenoloxidase (proPO) cascade. The
      temporal expression of LGBP and proPO genes in healthy and WSV-challenged Penaeus
      stylirostris shrimp was measured by real-time quantitative reverse transcription
      PCR, and we showed that LGBP gene expression in shrimp was upregulated as the WSV
      infection progressed. Interestingly, the proPO expression was upregulated
      initially after infection followed by a downregulation as the viral infection
      progressed. The downward trend in the expression of proPO coincided with the
      detection of WSV in the infected shrimp. Our data suggest that shrimp LGBP is an
      inducible acute-phase protein that may play a critical role in shrimp-WSV
      interaction and that the WSV infection regulates the activation and/or activity
      of the proPO cascade in a novel way.

PMID- 12072516
TI  - Herpes simplex virus type 1/adeno-associated virus hybrid vectors mediate site
      specific integration at the adeno-associated virus preintegration site, AAVS1, on
      human chromosome 19.
AB  - Herpes simplex virus type 1 (HSV-1)-based amplicon vectors have a large transgene
      capacity and can efficiently infect many different cell types. One disadvantage
      of HSV-1 vectors is their instability of transgene expression. By contrast,
      vectors based on adeno-associated virus (AAV) can either persist in an episomal
      form or integrate into the host cell genome, thereby supporting long-term gene
      expression. AAV expresses four rep genes, rep68, -78, -40, and -52. Of those,
      rep68 or rep78 are sufficient to mediate site-specific integration of the AAV DNA
      into the host cell genome. The major disadvantage of AAV vectors is the small
      transgene capacity ( approximately 4.6 kb). In this study, we constructed HSV/AAV
      hybrid vectors that contained, in addition to the standard HSV-1 amplicon
      elements, AAV rep68, rep78, both rep68 and -78, or all four rep genes and a
      reporter gene that was flanked by the AAV inverted terminal repeats (ITRs).
      Southern blots of Hirt DNA from cells transfected with the hybrid vectors and HSV
      1 helper DNA demonstrated that both the AAV elements and the HSV-1 elements were
      functional in the context of the hybrid vector. All hybrid vectors could be
      packaged into HSV-1 virions, although those containing rep sequences had lower
      titers than vectors that did not. Site-specific integration at AAVS1 on human
      chromosome 19 was directly demonstrated by PCR and sequence analysis of ITR-AAVS1
      junctions in hybrid vector-transduced 293 cells. Cell clones that stably
      expressed the transgene for at least 12 months could easily be isolated without
      chemical selection. In the majority of these clones, the transgene cassette was
      integrated at AAVS1, and no sequences outside the ITR cassette, rep in
      particular, were present as determined by PCR, ITR rescue/replication assays, and
      Southern analysis. Some of the clones contained random integrations of the
      transgene cassette alone or together with sequences outside the ITR cassette.
      These data indicate that the long-term transgene expression observed following
      transduction with HSV/AAV hybrid vectors is, at least in part, supported by
      chromosomal integration of the transgene cassette, both randomly and site
      specifically.

PMID- 12072515
TI  - Herpes simplex virus type 1/adeno-associated virus rep(+) hybrid amplicon vector
      improves the stability of transgene expression in human cells by site-specific
      integration.
AB  - Herpes simplex virus type 1 (HSV-1) amplicon vectors are promising gene delivery
      tools, but their utility in gene therapy has been impeded to some extent by their
      inability to achieve stable transgene expression. In this study, we examined the
      possibility of improving transduction stability in cultured human cells via site
      specific genomic integration mediated by adeno-associated virus (AAV) Rep and
      inverted terminal repeats (ITRs). A rep(-) HSV/AAV hybrid amplicon vector was
      made by inserting a transgene cassette flanked with AAV ITRs into an HSV-1
      amplicon backbone, and a rep(+) HSV/AAV hybrid amplicon was made by inserting
      rep68/78 outside the rep(-) vector 3' AAV ITR sequence. Both vectors also had a
      pair of loxP sites flanking the ITRs. The resulting hybrid amplicon vectors were
      successfully packaged and compared to a standard amplicon vector for stable
      transduction frequency (STF) in human 293 and Gli36 cell lines and primary
      myoblasts. The rep(+), but not the rep(-), hybrid vector improved STF in all
      three types of cells; 84% of Gli36 and 40% of 293 stable clones transduced by the
      rep(+) hybrid vector integrated the transgene into the AAVS1 site. Due to the
      difficulty in expanding primary myoblasts, we did not assess site-specific
      integration in these cells. A strategy to attempt further improvement of STF by
      "deconcatenating" the hybrid amplicon DNA via Cre-loxP recombination was tested,
      but it did not increase STF. These data demonstrate that introducing the
      integrating elements of AAV into HSV-1 amplicon vectors can significantly improve
      their ability to achieve stable gene transduction by conferring the AAV-like
      capability of site-specific genomic integration in dividing cells.

PMID- 12072517
TI  - Importance of the cytoplasmic tails of the measles virus glycoproteins for
      fusogenic activity and the generation of recombinant measles viruses.
AB  - The generation of replication-competent measles virus (MV) depends on the
      incorporation of biologically active, fusogenic glycoprotein complexes, which are
      required for attachment and penetration into susceptible host cells and for
      direct virus spread by cell-to-cell fusion. Whereas multiple studies have
      analyzed the importance of the ectodomains of the MV glycoproteins hemagglutinin
      (H) and fusion protein (F), we have investigated the role of the cytoplasmic
      tails of the F and H proteins for the formation of fusogenic complexes. Deletions
      in the cytoplasmic tails of transiently expressed MV glycoproteins were found to
      have varying effects on receptor binding, fusion, or fusion promotion activity. F
      tail truncation to only three amino acids did not affect fusion capacity. In
      contrast, truncation of the H cytoplasmic tail was limited. H protein mutants
      with cytoplasmic tails of <14 residues no longer supported F-mediated cell
      fusion, predominantly due to a decrease in surface expression and receptor
      binding. This indicates that a minimal length of the H protein tail of 14 amino
      acids is required to ensure a threshold local density to have sufficient
      accumulation of fusogenic H-F complexes. By using reverse genetics, a recombinant
      MV with an F tail of three amino acids (rMV-FcDelta30), as well as an MV with an
      H tail of 14 residues (rMV-HcDelta20), could be rescued, whereas generation of
      viruses with shorter H tails failed. Thus, glycoprotein truncation does not
      interfere with the successful generation of recombinant MV if fusion competence
      is maintained.

PMID- 12072519
TI  - Disruption of adherens junctions liberates nectin-1 to serve as receptor for
      herpes simplex virus and pseudorabies virus entry.
AB  - Nectin-1, a cell adhesion molecule belonging to the immunoglobulin superfamily,
      can bind to virion glycoprotein D (gD) to mediate entry of herpes simplex viruses
      (HSV) and pseudorabies virus (PRV). Nectin-1 colocalizes with E-cadherin at
      adherens junctions in epithelial cells. The disruption of cell junctions can
      result in the redistribution of nectin-1. To determine whether disruption of
      junctions by calcium depletion influenced the susceptibility of epithelial cells
      to viral entry, Madin-Darby canine kidney cells expressing endogenous nectin-1 or
      transfected human nectin-1 were tested for the ability to bind soluble forms of
      viral gD and to be infected by HSV and PRV, before and after calcium depletion.
      Confocal microscopy revealed that binding of HSV and PRV gD was localized to
      adherens junctions in cells maintained in normal medium but was distributed,
      along with nectin-1, over the entire cell surface after calcium depletion. Both
      the binding of gD and the fraction of cells that could be infected by HSV-1 and
      PRV were enhanced by calcium depletion. Taken together, these results provide
      evidence that nectin-1 confined to adherens junctions in epithelial cells is not
      very accessible to virus, whereas dissociation of cell junctions releases nectin
      1 to serve more efficiently as an entry receptor.

PMID- 12072520
TI  - RNA 3' readthrough of oncoretrovirus and lentivirus: implications for vector
      safety and efficacy.
AB  - The expression of reporter genes driven by the same human elongation factor
      1alpha (EF1alpha) promoter in murine leukemia virus (MLV)- and human
      immunodeficiency virus type 1 (HIV-1)-based vectors was studied in either
      transfected or virally transduced cells. The HIV-1 vectors consistently expressed
      3 to 10 times higher activity than the MLV vectors at both the RNA and protein
      levels. The difference was not attributable to transcriptional interference,
      alternative enhancer/silencer, or differential EF1alpha intron splicing. Based on
      nuclear run-on assays, both vectors exhibited similar EF1alpha transcriptional
      activity. The reduced RNA levels of MLV vectors could not be explained by the
      decrease in RNA half-lives. Southern analysis of proviral DNA indicated that both
      HIV-1 and MLV vectors efficiently propagated the EF1alpha intron in the
      transduced cells. To decipher the discrepancy in transgene expression between MLV
      and HIV-1 vectors, the role of RNA 3'-end processing was examined using a
      sensitive Cre/lox reporter assay. The results showed that MLV vectors, but not
      HIV-1 vectors, displayed high frequencies of readthrough of the 3'
      polyadenylation signal. Interestingly, the polyadenylation signal of a self
      inactivating (SIN) HIV-1 vector was as leaky as that of the MLV vectors,
      suggesting a potential risk of oncogene activation by the lentiviral SIN vectors.
      Together, our results suggest that an efficient polyadenylation signal would
      improve both the efficacy and the safety of these vectors.

PMID- 12072521
TI  - Further characterization of equine foamy virus reveals unusual features among the
      foamy viruses.
AB  - Foamy viruses (FVs) are nonpathogenic, widely spread complex retroviruses which
      have been isolated in nonhuman primates, cattle, cats, and more recently in
      horses. The equine foamy virus (EFV) was isolated from healthy horses and was
      characterized by molecular cloning and nucleotide sequence analysis. Here, to
      further characterize this new FV isolate, the location of the transcriptional cap
      and poly(A) addition sites as well as the main splice donor and acceptor sites
      were determined, demonstrating the existence of the specific subgenomic pol mRNA,
      one specific feature of FVs. Moreover, similar to what has been described for the
      human foamy virus (HFV), the prototype of FVs, a replication-defective EFV genome
      was identified during persistent infection. At the protein level, the use of
      specific antibodies allowed us to determine the size and the subcellular
      localization of EFV Gag, Env, and Tas, the viral transactivators. While EFV Gag
      was detected in both the cytoplasm and the nucleus, EFV Env mainly localized in
      the Golgi complex, in contrast to HFV Env, which is sequestered in the
      endoplasmic reticulum. In addition, electron microscopy analysis demonstrated
      that EFV budding occurs at the plasma membrane and not intracellularly, as is the
      case for primate FVs. Interestingly, EFV Tas was detected both in the nucleus and
      the cytoplasm of Tas-transfected cells, in contrast to the strict nuclear
      localization of other FV Tas but similar to the equine infectious anemia virus
      Tat gene product. Taken together, our results reveal that this new FV isolate
      exhibits remarkable features among FVs, bringing new insights into the biology of
      these unconventional retroviruses.

PMID- 12072518
TI  - Immunization of rhesus macaques with a DNA prime/modified vaccinia virus Ankara
      boost regimen induces broad simian immunodeficiency virus (SIV)-specific T-cell
      responses and reduces initial viral replication but does not prevent disease
      progression following challenge with pathogenic SIVmac239.
AB  - Producing a prophylactic vaccine for human immunodeficiency virus (HIV) has
      proven to be a challenge. Most biological isolates of HIV are difficult to
      neutralize, so that conventional subunit-based antibody-inducing vaccines are
      unlikely to be very effective. In the rhesus macaque model, some protection was
      afforded by DNA/recombinant viral vector vaccines. However, these studies used as
      the challenge virus SHIV-89.6P, which is neutralizable, making it difficult to
      determine whether the observed protection was due to cellular immunity, humoral
      immunity, or a combination of both. In this study, we used a DNA prime/modified
      vaccinia virus Ankara boost regimen to immunize rhesus macaques against nearly
      all simian immunodeficiency virus (SIV) proteins. These animals were challenged
      intrarectally with pathogenic molecularly cloned SIVmac239, which is resistant to
      neutralization. The immunization regimen resulted in the induction of virus
      specific CD8(+) and CD4(+) responses in all vaccinees. Although anamnestic
      neutralizing antibody responses against laboratory-adapted SIVmac251 developed
      after the challenge, no neutralizing antibodies against SIVmac239 were
      detectable. Vaccinated animals had significantly reduced peak viremia compared
      with controls (P < 0.01). However, despite the induction of virus-specific
      cellular immune responses and reduced peak viral loads, most animals still
      suffered from gradual CD4 depletion and progressed to disease.

PMID- 12072522
TI  - Characterization of varicella-zoster virus gene 21 and 29 proteins in infected
      cells.
AB  - Varicella-zoster virus (VZV) transcription is limited in latently infected human
      ganglia. Note that much of the transcriptional capacity of the virus genome has
      not been analyzed in detail; to date, only VZV genes mapping to open reading
      frames (ORFs) 4, 21, 29, 62, and 63 have been detected. ORF 62 encodes the major
      immediate-early virus transcription transactivator IE62, ORF 29 encodes the major
      virus DNA binding protein, and ORF 21 encodes a protein associated with the
      developing virus nucleocapsid. We analyzed the cellular location of proteins
      encoded by ORF 21 (21p) and ORF 29 (29p), their phosphorylation state during
      productive infection, and their ability form a protein-protein complex. The
      locations of both 21p and 29p within infected cells mimic those of their herpes
      simplex virus type 1 (HSV-1) homologues (UL37 and ICP8); however, unlike these
      homologues, 21p is not phosphorylated and neither 21p nor 29p exhibits a protein
      protein interaction. Transient transfection assays to determine the effect of 21p
      and 29p on transcription from VZV gene 20, 21, 28, and 29 promoters revealed no
      significant activation of transcription by 21p or 29p from any of the VZV gene
      promoters tested, and 21p did not significantly modulate the ability of IE62 to
      activate gene transcription. A modest increase in IE62-induced activation of gene
      28 and 29 promoters was seen in the presence of 29p; however, IE62-induced
      activation of gene 28 and 29 promoters was reduced in the presence of 21p. A
      Saccharomyces cerevisiae two-hybrid analysis of 21p indicated that the protein
      can activate transcription when tethered within a responsive promoter. Together,
      the data reveal that while VZV gene 21 and HSV-1 UL37 share homology at the
      nucleic acid level, these proteins differ functionally.

PMID- 12072523
TI  - Aura virus structure suggests that the T=4 organization is a fundamental property
      of viral structural proteins.
AB  - Aura and Sindbis viruses are closely related alphaviruses. Unlike other
      alphaviruses, Aura virus efficiently encapsidates both genomic RNA (11.8 kb) and
      subgenomic RNA (4.2 kb) to form virus particles. Previous studies on negatively
      stained Aura virus particles predicted that there were two major size classes
      with potential T=3 and T=4 capsid structures. We have used cryoelectron
      microscopy and three-dimensional image reconstruction techniques to examine the
      native morphology of different classes of Aura virus particles produced in BHK
      cells. Purified particles separated into two components in a sucrose gradient.
      Reconstructions of particles in the top and bottom components were computed to
      resolutions of 17 and 21 A, respectively, and compared with reconstructions of
      Sindbis virus and Ross River virus particles. Aura virus particles of both top
      and bottom components have similar, T=4 structures that resemble those of other
      alphaviruses. The morphology of Aura virus glycoprotein spikes closely resembles
      that of Sindbis virus spikes and is detectably different from that of Ross River
      virus spikes. Thus, some aspects of the surface structure of members of the
      Sindbis virus lineage have been conserved, but other aspects have diverged from
      the Semliki Forest/Ross River virus lineage.

PMID- 12072524
TI  - Reactivation of latent cytomegalovirus infection in mouse brain cells detected
      after transfer to brain slice cultures.
AB  - Cytomegalovirus (CMV) is the most significant infectious cause of brain disorders
      in humans involving the developing brain. It is hypothesized that the brain
      disorders occur after recurrent reactivation of the latent infection in some
      kinds of cells in the brains. In order to test this hypothesis, we examined the
      reactivation of latent murine CMV (MCMV) infection in the mouse brain by transfer
      to brain slice culture. We infected neonatal and young adult mice intracerebrally
      with recombinant MCMV in which the lacZ gene was inserted into a late gene. The
      brains were removed 6 months after infection and used to prepare brain slices
      that were then cultured for up to 4 weeks. Reactivation of latent infection in
      the brains was detected by beta-galactosidase (beta-Gal) staining to assess beta
      galactosidase expression. Viral replication was also confirmed by the plaque
      assay. Reactivation was observed in about 75% of the mice infected during the
      neonatal period 6 months after infection. Unexpectedly, reactivation was also
      observed in 75% of mice infected as young adults, although the infection ratio in
      the brain slices was significantly lower than that in neonatally infected mice.
      Beta-Gal-positive cells were observed in marginal regions of the brains or
      immature neural cells in the ventricular walls. Immunohistochemical staining
      showed that the beta-Gal-positive reactivated cells were neural stem or
      progenitor cells. These results suggest that brain disorders may occur long after
      infection by reactivation of latent infection in the immature neural cells in the
      brain.

PMID- 12072525
TI  - Amino acid substitutions in the V domain of nectin-1 (HveC) that impair entry
      activity for herpes simplex virus types 1 and 2 but not for Pseudorabies virus or
      bovine herpesvirus 1.
AB  - The entry of herpes simplex virus (HSV) into cells requires the interaction of
      viral glycoprotein D (gD) with a cellular gD receptor to trigger the fusion of
      viral and cellular membranes. Nectin-1, a member of the immunoglobulin
      superfamily, can serve as a gD receptor for HSV types 1 and 2 (HSV-1 and HSV-2,
      respectively) as well as for the animal herpesviruses porcine pseudorabies virus
      (PRV) and bovine herpesvirus 1 (BHV-1). The HSV-1 gD binding domain of nectin-1
      is hypothesized to overlap amino acids 64 to 104 of the N-terminal variable
      domain-like immunoglobulin domain. Moreover, the HSV-1 and PRV gDs compete for
      binding to nectin-1. Here we report that two amino acids within this region, at
      positions 77 and 85, are critical for HSV-1 and HSV-2 entry but not for the entry
      of PRV or BHV-1. Replacement of either amino acid 77 or amino acid 85 reduced HSV
      1 and HSV-2 gD binding but had a lesser effect on HSV entry activity, suggesting
      that weak interactions between gD and nectin-1 are sufficient to trigger the
      mechanism of HSV entry. Substitution of both amino acid 77 and amino acid 85 in
      nectin-1 significantly impaired entry activity for HSV-1 and HSV-2 and eliminated
      binding to soluble forms of HSV-1 and HSV-2 gDs but did not impair the entry of
      PRV and BHV-1. Thus, amino acids 77 and 85 of nectin-1 form part of the interface
      with HSV gD or influence the conformation of that interface. Moreover, the
      binding sites for HSV and PRV or BHV-1 gDs on nectin-1 may overlap but are not
      identical.

PMID- 12072526
TI  - Characterization of the glycoproteins of Crimean-Congo hemorrhagic fever virus.
AB  - Crimean-Congo hemorrhagic fever (CCHF) virus is the cause of an important tick
      borne disease of humans throughout regions of Africa, Europe, and Asia. Like
      other members of the genus Nairovirus, family Bunyaviridae, the CCHF virus M
      genome RNA segment encodes the virus glycoproteins. Sequence analysis of the CCHF
      virus (Matin strain) M RNA segment revealed one major open reading frame that
      potentially encodes a precursor polyprotein 1,689 amino acids (aa) in length.
      Comparison of the deduced amino acid sequences of the M-encoded polyproteins of
      Nigerian, Pakistani, and Chinese CCHF virus strains revealed two distinct protein
      regions. The carboxyl-terminal 1,441 aa are relatively highly conserved (up to
      8.4% identity difference), whereas the amino-terminal 243 to 248 aa are highly
      variable (up to 56.4% identity difference) and have mucin-like features,
      including a high serine, threonine, and proline content (up to 47.3%) and a
      potential for extensive O-glycosylation. Analysis of released virus revealed two
      major structural glycoproteins, G2 (37 kDa) and G1 (75 kDa). Virus protein
      analysis by various techniques, including pulse-chase analysis and/or reactivity
      with CCHF virus-specific polyclonal and antipeptide antibodies, demonstrated that
      the 140-kDa (which contains the mucin-like region) and 85-kDa nonstructural
      proteins are the precursors of the mature G2 and G1 proteins, respectively. The
      amino termini of the CCHF virus (Matin strain) G2 and G1 proteins were
      established by microsequencing to be equivalent to aa 525 and 1046, respectively,
      of the encoded polyprotein precursor. The tetrapeptides RRLL and RKPL are
      immediately upstream of the cleavage site for mature G2 and G1, respectively.
      These are completely conserved among the predicted polyprotein sequences of all
      the CCHF virus strains and closely resemble the tetrapeptides that represent the
      major cleavage recognition sites present in the glycoprotein precursors of
      arenaviruses, such as Lassa fever virus (RRLL) and Pichinde virus (RKLL). These
      results strongly suggest that CCHF viruses (and other members of the genus
      Nairovirus) likely utilize the subtilase SKI-1/S1P-like cellular proteases for
      the major glycoprotein precursor cleavage events, as has recently been
      demonstrated for the arenaviruses.

PMID- 12072527
TI  - Identification of the neoplastically transformed cells in Marek's disease
      herpesvirus-induced lymphomas: recognition by the monoclonal antibody AV37.
AB  - Understanding the interactions between herpesviruses and their host cells and
      also the interactions between neoplastically transformed cells and the host
      immune system is fundamental to understanding the mechanisms of herpesvirus
      oncology. However, this has been difficult as no animal models of herpesvirus
      induced oncogenesis in the natural host exist in which neoplastically transformed
      cells are also definitively identified and may be studied in vivo. Marek's
      disease (MD) herpesvirus (MDV) of poultry, although a recognized natural
      oncogenic virus causing T-cell lymphomas, is no exception. In this work, we
      identify for the first time the neoplastically transformed cells in MD as the
      CD4(+) major histocompatibility complex (MHC) class I(hi), MHC class II(hi),
      interleukin-2 receptor alpha-chain-positive, CD28(lo/-), phosphoprotein 38
      negative (pp38(-)), glycoprotein B-negative (gB(-)), alphabeta T-cell-receptor
      positive (TCR(+)) cells which uniquely overexpress a novel host-encoded
      extracellular antigen that is also expressed by MDV-transformed cell lines and
      recognized by the monoclonal antibody (MAb) AV37. Normal uninfected leukocytes
      and MD lymphoma cells were isolated directly ex vivo and examined by flow
      cytometry with MAb recognizing AV37, known leukocyte antigens, and MDV antigens
      pp38 and gB. CD28 mRNA was examined by PCR. Cell cycle distribution and in vitro
      survival were compared for each lymphoma cell population. We demonstrate for the
      first time that the antigen recognized by AV37 is expressed at very low levels by
      small minorities of uninfected leukocytes, whereas particular MD lymphoma cells
      uniquely express extremely high levels of the AV37 antigen; the AV37(hi) MD
      lymphoma cells fulfill the accepted criteria for neoplastic transformation in
      vivo (protection from cell death despite hyperproliferation, presence in all MD
      lymphomas, and not supportive of MDV production); the lymphoma environment is
      essential for AV37(+) MD lymphoma cell survival; pp38 is an antigen expressed
      during MDV-productive infection and is not expressed by neoplastically
      transformed cells in vivo; AV37(+) MD lymphoma cells have the putative immune
      evasion mechanism of CD28 down-regulation; AV37(hi) peripheral blood leukocytes
      appear early after MDV infection in both MD-resistant and -susceptible chickens;
      and analysis of TCR variable beta chain gene family expression suggests that MD
      lymphomas have polyclonal origins. Identification of the neoplastically
      transformed cells in MD facilitates a detailed understanding of MD pathogenesis
      and also improves the utility of MD as a general model for herpesvirus oncology.

PMID- 12072528
TI  - The mannose-dependent epitope for neutralizing antibody 2G12 on human
      immunodeficiency virus type 1 glycoprotein gp120.
AB  - We have analyzed the unique epitope for the broadly neutralizing human monoclonal
      antibody (MAb) 2G12 on the gp120 surface glycoprotein of human immunodeficiency
      virus type 1 (HIV-1). Sequence analysis, focusing on the conservation of relevant
      residues across multiple HIV-1 isolates, refined the epitope that was defined
      previously by substitutional mutagenesis (A. Trkola, M. Purtscher, T. Muster, C.
      Ballaun, A. Buchacher, N. Sullivan, K. Srinivasan, J. Sodroski, J. P. Moore, and
      H. Katinger, J. Virol. 70:1100-1108, 1996). In a biochemical study, we digested
      recombinant gp120 with various glycosidase enzymes of known specificities and
      showed that the 2G12 epitope is lost when gp120 is treated with mannosidases.
      Computational analyses were used to position the epitope in the context of the
      virion-associated envelope glycoprotein complex, to determine the variability of
      the surrounding surface, and to calculate the surface accessibility of possible
      glycan- and polypeptide-epitope components. Together, these analyses suggest that
      the 2G12 epitope is centered on the high-mannose and/or hybrid glycans of
      residues 295, 332, and 392, with peripheral glycans from 386 and 448 on either
      flank. The epitope is mannose dependent and composed primarily of carbohydrate,
      with probably no direct involvement of the gp120 polypeptide surface. It resides
      on a face orthogonal to the CD4 binding face, on a surface proximal to, but
      distinct from, that implicated in coreceptor binding. Its conservation amidst an
      otherwise highly variable gp120 surface suggests a functional role for the 2G12
      binding site, perhaps related to the mannose-dependent attachment of HIV-1 to DC
      SIGN or related lectins that facilitate virus entry into susceptible target
      cells.

PMID- 12072530
TI  - Modulating the function of the measles virus RNA-dependent RNA polymerase by
      insertion of green fluorescent protein into the open reading frame.
AB  - Measles virus (MV) is the type species of the Morbillivirus genus and its RNA
      dependent RNA polymerase complex is comprised of two viral polypeptides, the
      large (L) and the phospho- (P) proteins. Sequence alignments of morbillivirus L
      polymerases have demonstrated the existence of three well-conserved domains (D1,
      D2, and D3) which are linked by two variable hinges (H1 and H2). Epitope tags (c
      Myc) were introduced into H1 and H2 to investigate the tolerance of the variable
      regions to insertions and to probe the flexibility of the proposed domain
      structures to spatial reorientation. Insertion into H1 abolished polymerase
      activity whereas introduction into H2 had no effect. The open reading frame of
      enhanced green fluorescent protein was also inserted into the H2 region of the MV
      L gene to extend these observations. This resulted in a recombinant protein that
      was both functional and autofluorescent, although the overall polymerase activity
      was reduced by over 40%. Two recombinant viruses which contained the chimeric L
      genes EdtagL(MMc-mycM) and EdtagL(MMEGFPM) were generated. Tagged L proteins were
      detectable, by indirect immunofluorescence in the case of EdtagL(MMc-mycM) and by
      autofluorescence in the case of EdtagL(MMEGFPM). We suggest that D3 enjoys a
      limited conformational independence from the other domains, indicating that the L
      polymerases of the Mononegavirales may function as multidomain proteins.

PMID- 12072531
TI  - CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon
      in mice infected with mouse hepatitis virus.
AB  - Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM
      (MHV) develop an immune-mediated demyelinating encephalomyelitis. Adoptive
      transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to
      infected mice deficient in recombination activation gene 1 resulted in
      demyelination. We showed previously that the process of CD8 T-cell-mediated
      demyelination was strongly dependent on the expression of gamma interferon (IFN
      gamma) by donor cells. In this report, we show, in contrast, that demyelination
      and lymphocyte infiltration were increased in recipients of IFN-gamma(-/-) CD4 T
      cells when compared to levels in mice receiving C57BL/6 CD4 T cells.

PMID- 12072529
TI  - The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12
      recognizes a cluster of alpha1-->2 mannose residues on the outer face of gp120.
AB  - 2G12 is a broadly neutralizing human monoclonal antibody against human
      immunodeficiency virus type-1 (HIV-1) that has previously been shown to bind to a
      carbohydrate-dependent epitope on gp120. Here, site-directed mutagenesis and
      carbohydrate analysis were used to define further the 2G12 epitope. Extensive
      alanine scanning mutagenesis showed that elimination of the N-linked carbohydrate
      attachment sequences associated with residues N295, N332, N339, N386, and N392 by
      N-->A substitution produced significant decreases in 2G12 binding affinity to
      gp120(JR-CSF). Further mutagenesis suggested that the glycans at N339 and N386
      were not critical for 2G12 binding to gp120(JR-CSF). Comparison of the sequences
      of isolates neutralized by 2G12 was also consistent with a lesser role for
      glycans attached at these positions. The mutagenesis studies provided no
      convincing evidence for the involvement of gp120 amino acid side chains in 2G12
      binding. Antibody binding was inhibited when gp120 was treated with Aspergillus
      saitoi mannosidase, Jack Bean mannosidase, or endoglycosidase H, indicating that
      Man(alpha)1-->2Man-linked sugars of oligomannose glycans on gp120 are required
      for 2G12 binding. Consistent with this finding, the binding of 2G12 to gp120
      could be inhibited by monomeric mannose but not by galactose, glucose, or N
      acetylglucosamine. The inability of 2G12 to bind to gp120 produced in the
      presence of the glucose analogue N-butyl-deoxynojirimycin similarly implicated
      Man(alpha)1-->2Man-linked sugars in 2G12 binding. Competition experiments between
      2G12 and the lectin cyanovirin for binding to gp120 showed that 2G12 only
      interacts with a subset of available Man(alpha)1-->2Man-linked sugars.
      Consideration of all the data, together with inspection of a molecular model of
      gp120, suggests that the most likely epitope for 2G12 is formed from mannose
      residues contributed by the glycans attached to N295 and N332, with the other
      glycans playing an indirect role in maintaining epitope conformation.

PMID- 12072532
TI  - Evaluation of Tat-encoding bicistronic human immunodeficiency virus type 1 gene
      transfer vectors in primary canine bone marrow mononuclear cells.
AB  - Tat-encoding human immunodeficiency virus type 1 (HIV-1) gene transfer vectors
      were evaluated in primary canine bone marrow mononuclear cells. Tat vectors
      provided higher levels of gene expression than vectors with internal promoters.
      The HIV-1 vector was also more efficient than Moloney murine leukemia virus
      (MoMLV) vectors for transduction of canine bone marrow mononuclear cells in
      vitro. Transplantation experiments in dogs with transduced autologous marrow
      cells confirmed the superiority of HIV-1 vectors over MoMLV vectors for gene
      transfer into canine bone marrow cells. Tat vectors may be useful not only for
      providing high levels of therapeutic gene expression in hematopoietic cells but
      also for study of the biological effects of Tat in those tissues in the canine
      model.

PMID- 12072533
TI  - PG13 packaging cells produce recombinant retroviruses carrying a diphtheria toxin
      mutant which kills cancer cells.
AB  - The development of suicide gene therapy with gene products that are directly
      toxic to cells, such as the A subunit of diphtheria toxin (DT-A), has been
      hampered by the difficulty of engineering recombinant viruses. DT-A is a strong
      inhibitor of protein synthesis that acts by ADP-ribosylating elongation factor 2,
      and a low level of DT-A expression in virus producer cells prevents the
      production of recombinant virus. We analyzed here the natural resistance of
      packaging cells to DT-A toxicity, and we report that PG13 and PA317 packaging
      cell lines are resistant to H21G, a DT-A mutant. PG13 cells produce recombinant
      H21G virus that efficiently kills a variety of human tumor cells. Our finding
      indicates that PG13 packaging cells provide a new potential for the development
      of DT-A-based suicide gene therapy.

PMID- 12072534
TI  - The EBNA2 polyproline region is dispensable for Epstein-Barr virus-mediated
      immortalization maintenance.
AB  - Epstein-Barr virus nuclear antigen 2 (EBNA2) is required for EBV-mediated
      immortalization of primary human B cells and is a direct transcriptional
      activator of viral and cellular genes. The prototype EBNA2 protein contains a
      unique motif in which 43 out of 45 amino acids are prolines (polyproline region
      [PPR]). Previous genetic analysis has shown that deletion of the PPR resulted in
      viruses unable to immortalize B cells, although the protein did appear
      transcriptionally functional (R. Yalamanchili, S. Harada, and E. Kieff, J. Virol.
      70:2468-2473, 1996). The PPR's uniqueness and requirement for immortalization
      make it an attractive therapeutic target. However, the role of this highly
      unusual motif for immortalization remains enigmatic. We have recently developed a
      transcomplementation assay that allows both genetic and functional analyses of
      EBNA2 in EBV-mediated immortalization maintenance (A. V. Gordadze, R. Peng, J.
      Tan, G. Liu, R. Sutton, B. Kempkes, G. W. Bornkamm, and P. D. Ling, J. Virol.
      75:5899-5912, 2001). Surprisingly, we found that DeltaPPR-EBNA2 was able to
      support B-cell proliferation similar to that of wild-type EBNA2 in this assay,
      indicating that deletion of the PPR from EBNA2 does not result in a loss of
      function required for immortalization maintenance. Further analysis of this
      mutant EBNA2 revealed that it consistently activated the viral LMP1 and LMP2A
      promoters severalfold better than wild-type EBNA2 in transient cotransfection
      assays. In addition, one striking difference between lymphoblastoid cell lines
      expressing wild-type EBNA2 from those expressing DeltaPPR-EBNA2 is that the
      latter cells have significantly reduced EBV genomic levels. The data are
      consistent with a model in which lower EBNA2 target gene dosage may be selected
      for in DeltaPPR-EBNA2-dependent cell lines to compensate for hyperactive
      stimulation of viral genes, such as LMP-1, which is cytostatic for B cells when
      overexpressed. It is conceivable that the hyperactivity rather than the loss of
      function, as hypothesized previously, could be responsible for the inability of
      recombinant DeltaPPR-EBNA2 EBVs to immortalize B cells.

PMID- 12072536
TI  - Genetic epidemiology of melanoma: of consortia and conundrums.

PMID- 12072537
TI  - Breaking the silence: the rise of epigenetic therapy.

PMID- 12072535
TI  - Genetic evidence that interhelical packing interactions in the gp41 core are
      critical for transition of the human immunodeficiency virus type 1 envelope
      glycoprotein to the fusion-active state.
AB  - The envelope glycoprotein complex (gp120-gp41) of human immunodeficiency virus
      type 1 (HIV-1) promotes the fusion of viral and cellular membranes through
      formation of the fusion-active six-helix bundle in the gp41 ectodomain. This gp41
      core structure consists of three C-terminal helices packed in an antiparallel
      manner into hydrophobic grooves on the surface of the N-terminal trimeric coiled
      coil. Alanine mutations that destabilize the N- and C-terminal interhelical
      packing interactions also reduce viral infectivity. Here we show that viruses
      bearing these mutations exhibit a marked potentiation of inhibition by peptides
      that make up the gp41 core. By contrast, these viruses are unchanged in their
      sensitivities to soluble CD4, the CXCR4 coreceptor ligand SDF-1alpha, and human
      anti-HIV immunoglobulin, reagents that impact the initial, receptor-induced
      conformational changes in the envelope glycoprotein. Our results support the
      notion that these alanine mutations specifically affect the conformational
      transition to the fusion-active gp41 structure. The mutations also increase viral
      sensitivity to the gp41-directed monoclonal antibody 2F5, suggesting that this
      broadly neutralizing antibody may also interfere with this transition. The
      conformational activation of the HIV-1 envelope glycoprotein likely represents a
      viable target for vaccine and antiviral drug development.

PMID- 12072538
TI  - Acrylamide and cancer: tunnel leak in Sweden prompted studies.

PMID- 12072539
TI  - New Pap test terminology, management guidelines published.

PMID- 12072540
TI  - Frequency of cervical cancer screening by age group, 2000.

PMID- 12072541
TI  - Guidelines for abnormal Pap tests: do physicians follow them?

PMID- 12072542
TI  - Clinical application of antiangiogenic therapy: microvessel density, what it does
      and doesn't tell us.

PMID- 12072543
TI  - Geographical variation in the penetrance of CDKN2A mutations for melanoma.
AB  - BACKGROUND: Germline mutations in the CDKN2A gene, which encodes two proteins
      (p16INK4A and p14ARF), are the most common cause of inherited susceptibility to
      melanoma. We examined the penetrance of such mutations using data from eight
      groups from Europe, Australia and the United States that are part of The Melanoma
      Genetics Consortium. METHODS: We analyzed 80 families with documented CDKN2A
      mutations and multiple cases of cutaneous melanoma. We modeled penetrance for
      melanoma using a logistic regression model incorporating survival analysis.
      Hypothesis testing was based on likelihood ratio tests. Covariates included
      gender, alterations in p14ARF protein, and population melanoma incidence rates.
      All statistical tests were two-sided. RESULTS: The 80 analyzed families contained
      402 melanoma patients, 320 of whom were tested for mutations and 291 were
      mutation carriers. We also tested 713 unaffected family members for mutations and
      194 were carriers. Overall, CDKN2A mutation penetrance was estimated to be 0.30
      (95% confidence interval (CI) = 0.12 to 0.62) by age 50 years and 0.67 (95% CI =
      0.31 to 0.96) by age 80 years. Penetrance was not statistically significantly
      modified by gender or by whether the CDKN2A mutation altered p14ARF protein.
      However, there was a statistically significant effect of residing in a location
      with a high population incidence rate of melanoma (P =.003). By age 50 years
      CDKN2A mutation penetrance reached 0.13 in Europe, 0.50 in the United States, and
      0.32 in Australia; by age 80 years it was 0.58 in Europe, 0.76 in the United
      States, and 0.91 in Australia. CONCLUSIONS: This study, which gives the most
      informed estimates of CDKN2A mutation penetrance available, indicates that the
      penetrance varies with melanoma population incidence rates. Thus, the same
      factors that affect population incidence of melanoma may also mediate CDKN2A
      penetrance.

PMID- 12072544
TI  - Changing area socioeconomic patterns in U.S. cancer mortality, 1950-1998: Part I-
      All cancers among men.
AB  - BACKGROUND: Area socioeconomic deprivation indices are widely used to monitor
      health disparities in Europe. However, such indices have not been used in cancer
      surveillance in the United States. We developed an area socioeconomic index to
      examine area socioeconomic patterns in all-cancer mortality among U.S. men
      between 1950 and 1998. METHODS: Principal components analysis on 11 census
      variables was used to develop an area socioeconomic index that was then used to
      stratify all U.S. counties into one of five socioeconomic categories. The index
      was linked to 1950-1998 county mortality data to generate annual mortality rates
      for each area socioeconomic group. Joinpoint regression analysis was used to
      model mortality trends, and Poisson regression analysis was used to estimate
      socioeconomic gradients in mortality over time. RESULTS: Area socioeconomic
      patterns in U.S. male cancer mortality changed dramatically between 1950 and
      1998. Throughout the 1950s and 1960s, there was a positive socioeconomic
      gradient, with higher cancer mortality rates in high area socioeconomic groups
      than in low area socioeconomic groups. For example, in 1950-1952, cancer
      mortality was 49% (95% confidence interval [CI] = 41% to 59%) greater in the
      highest area socioeconomic group than in the lowest. The positive gradient
      narrowed in the 1970s, and by the late 1980s, socioeconomic differences in cancer
      mortality began to reverse and widen. In 1997-1998, cancer mortality was 19% (95%
      CI = 11% to 28%) higher in the lowest area socioeconomic group than in the
      highest. Gradients were steeper for men aged 25-64 years than for men aged 65
      years or older. CONCLUSIONS: Socioeconomic patterns in male cancer mortality have
      reversed over time in the United States. Area socioeconomic indices could serve
      as a powerful surveillance tool for monitoring health disparities in cancer
      outcomes.

PMID- 12072545
TI  - Changing area socioeconomic patterns in U.S. cancer mortality, 1950-1998: Part II
      -Lung and colorectal cancers.
AB  - BACKGROUND: Lung cancer and colorectal cancer are leading causes of U.S. cancer
      mortality. Because mortality rates for many cancers vary by socioeconomic
      characteristics, we used area socioeconomic indices to examine patterns in U.S.
      lung and colorectal cancer mortality between 1950 and 1998. METHODS: A factor
      based area socioeconomic index was linked to 1950-1998 county mortality data to
      generate annual lung and colorectal cancer mortality rates for each area
      socioeconomic group. Joinpoint regression analysis was used to model and identify
      statistically significant changes in the mortality trends. RESULTS: Area
      socioeconomic patterns in U.S. lung cancer mortality changed dramatically between
      1950 and 1998. Men aged 25-64 years and those aged 65 years or older in higher
      socioeconomic areas generally had higher lung cancer mortality than did those in
      lower socioeconomic areas during 1950-1964 and 1950-1980, respectively. Area
      socioeconomic differences in lung cancer mortality began to reverse and widen by
      the early 1970s for younger men and by the mid-1980s for older men. In 1998, lung
      cancer mortality was 56% (95% confidence interval [CI] = 49% to 64%) higher for
      younger men and 38% higher (95% CI = 34% to 43%) for older men in the lowest area
      socioeconomic group than for the same age groups in the highest area
      socioeconomic group. Lung cancer mortality among older women in all socioeconomic
      groups increased sevenfold to eightfold between 1950 and 1998, with higher
      mortality in higher area socioeconomic groups. The positive socioeconomic
      gradient in colorectal cancer mortality diminished substantially over time.
      Although colorectal cancer mortality among women in all area socioeconomic groups
      showed a consistent downward trend, colorectal cancer mortality among men in low
      area socioeconomic groups, but not in high area socioeconomic groups, showed an
      upward trend. CONCLUSIONS: Socioeconomic gradients in male lung cancer mortality
      reversed between 1950 and 1998, and those in colorectal cancer mortality narrowed
      over that time. Area measures may be useful for monitoring socioeconomic
      disparities in cancer mortality and for identifying areas for potential cancer
      control interventions.

PMID- 12072546
TI  - Tumorigenesis and aberrant signaling in transgenic mice expressing the human
      herpesvirus-8 K1 gene.
AB  - BACKGROUND: The K1 gene of human herpesvirus-8 (HHV-8; also known as Kaposi's
      sarcoma-associated herpesvirus) encodes a transmembrane signaling protein that
      elicits cellular activation events. To evaluate the potential role of K1 in HHV-8
      associated pathogenesis, we produced transgenic mice expressing the HHV-8 K1 gene
      under the transcriptional control of the simian virus 40 promoter. METHODS: Three
      independent heterozygous transgenic K1 mouse lines were generated from founder
      mice. Mouse splenic and thymic lymphocytes and tumor tissues were analyzed for
      the expression of cytokines involved in inflammatory and immune responses,
      including tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), basic
      fibroblast growth factor (bFGF), and interleukin 12 (IL-12); for the activation
      of the transcription factors nuclear factor-kappaB (NF-kappaB) and the B cell
      specific transcription factor Oct-2; and for the activation of the Src and Syk
      family kinases, components of B-cell receptor-induced signal-transduction
      pathways. RESULTS: Expression of bFGF was increased in K1-transgenic mice as
      compared with nontransgenic mice, whereas expression of TNF-alpha and IL-6 did
      not differ using reverse transcriptase-polymerase chain reaction. K1-transgenic
      mice showed substantially less serum IL-12 induction than did nontransgenic mice
      when challenged with a lipopolysaccharide. B lymphocytes from K1-transgenic mice
      but not from nontransgenic mice showed constitutive activation of NF-kappaB and
      Oct-2. K1 expression in human B lymphocytes stimulated NF-kappaB-dependent
      promoter activity. B lymphocytes from K1-transgenic mice also showed increased
      phosphorylation of Lyn, a Src family tyrosine kinase, and enhanced Lyn activity.
      Tumors in K1-transgenic mice showed features indicative of a spindle-cell
      sarcomatoid tumor and a malignant plasmablastic lymphoma. The pattern of
      cytokine, transcription factor, and Lyn kinase activity in the lymphoma was
      similar to that in B lymphocytes from K1-transgenic mice. CONCLUSION: K1 may be
      involved in the activation of NF-kappaB signaling. The enhanced NF-kappaB
      activity in nonmalignant lymphocytes of K1 mice and its persistence in lymphoma
      tumors of these mice suggest that the K1 mouse may be a model of premalignancy.

PMID- 12072547
TI  - Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism
      and survival of patients with metastatic colorectal cancer.
AB  - BACKGROUND: Members of the glutathione S-transferase (GST) superfamily are
      important in cellular defense mechanisms. These enzymes attach reduced
      glutathione to electrophilic groups in a wide variety of toxic compounds,
      including chemotherapeutic agents. Certain polymorphisms in GSTs are associated
      with changes in enzyme activity, sensitivity to chemotherapy, and overall patient
      survival. In a retrospective study, we investigated associations between common
      polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and
      survival of patients with metastatic colorectal cancer receiving 5-fluorouracil
      (5-FU)/oxaliplatin chemotherapy. METHODS: During 1998-2000, 107 previously
      treated patients with advanced colorectal cancer received 5-FU/oxaliplatin
      combination chemotherapy. Associations between deletion polymorphisms in GSTM1
      and GSTT1 genes and between a polymorphism in the GSTP1 gene that generates an
      Ile(105)Val in the GSTP1 protein and survival were evaluated using relative risks
      (RRs) of dying and the log-rank test. All statistical tests were two-sided.
      RESULTS: Patients heterozygous for the GSTP1 polymorphism had an RR = 0.47 (95%
      confidence interval [CI] = 0.27 to 0.81) compared with patients homozygous for
      the GSTP1 (105)Ile allele. Patients homozygous for the mutant polymorphism had an
      RR = 0.16 (95% CI = 0.04 to 0.63). After adjustment for performance status and
      tumor site, the stratified RRs were 0.28 (95% CI = 0.07 to 1.10) for patients
      with two (105)Val alleles and 0.64 (95% CI = 0.36 to 1.16) for those with one
      (105)Val allele (P =.042). Patients with the (105)Val/(105)Val genotype survived
      a median of 24.9 months, those with the (105)Ile/(105)Ile genotype a median of
      7.9 months, and those with the (105)Ile/(105)Val genotype a median of 13.3 months
      (P<.001). The GSTM1 and GSTT1 genotypes were not associated with survival or
      clinical response. CONCLUSIONS: The GSTP1 Ile(105)Val polymorphism is associated
      in a dose-dependent fashion with increased survival of patients with advanced
      colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.

PMID- 12072548
TI  - Breast cancer mortality among female radiologic technologists in the United
      States.
AB  - We evaluated breast cancer mortality through 1997 among 69 525 female radiologic
      technologists who were certified in the United States from 1926 through 1982 and
      who responded to our questionnaire. Risk of breast cancer mortality was examined
      according to work history and practices and was adjusted for known risk factors.
      Breast cancer mortality risk was highest among women who were first employed as
      radiologic technologists prior to 1940 (relative risk [RR] = 2.92, 95% confidence
      interval [CI] = 1.22 to 7.00) compared with risk of those first employed in 1960
      or later and declined with more recent calendar year of first employment (P for
      trend =.002). Breast cancer mortality risk increased with increasing number of
      years of employment as a technologist prior to 1950 (P for trend =.018). However,
      risk was not associated with the total number of years a woman worked as a
      technologist. Technologists who first performed fluoroscopy (RR = 1.69, 95% CI =
      1.02 to 3.11) and multifilm procedures (RR = 1.87, 95% CI = 1.04 to 3.34) before
      1950 had statistically significantly elevated risks compared with technologists
      who first performed these procedures in 1960 or later. The high risks of breast
      cancer mortality for women exposed to occupational radiation prior to 1950 and
      the subsequent decline in risk are consistent with the dramatic reduction in
      recommended radiation exposure limits over time.

PMID- 12072549
TI  - Re: Effects of N-(4-hydroxy-phenyl)retinamide on hTERT expression in the
      bronchial epithelium of cigarette smokers.

PMID- 12072550
TI  - Re: Gamma-radiation sensitivity and risk of glioma.

PMID- 12072552
TI  - Re: Dominant negative ATM mutations in breast cancer families.

PMID- 12072555
TI  - Analysis of glutamate receptor surface expression in acute hippocampal slices.
AB  - Trafficking of receptors to and from the cell surface is a powerful mechanism for
      regulating neuronal excitability. To date, the majority of studies concerning
      glutamate receptor trafficking have been performed in neuronal cultures in which
      surface expression can be readily assayed by immunofluorescence techniques.
      Results from such studies have had important implications in the field of
      synaptic plasticity. However, cultured neurons are, by necessity, prepared from
      very young animals. Moreover, although an enhancement of excitatory
      neurotransmission can be induced in such systems, classic long-term potentiation
      (LTP) can be produced only in acute slices or in vivo. To study trafficking in
      adult tissues, we have adapted two biochemical techniques, proteolysis and cross
      linking. These techniques help define surface-expressed and intracellular pools
      of native receptors in acute hippocampal slices.

PMID- 12072556
TI  - Homer as both a scaffold and transduction molecule.
AB  - Increasing evidence shows that scaffold proteins not only control membrane
      assembly of receptors and channels, but also modulate intracellular signaling by
      assembled receptors. The Homer family of proteins act as scaffolds to bind
      clusters of proteins and glutamate receptors at postsynaptic sites. We review
      results of cloning and gene expression of this protein family, and summarize
      roles in glutamate receptor function and intracellular signaling in neurons.
      Homer proteins trigger the localization of metabotropic glutamate receptor
      subtype 5 (mGlu5 receptor) to the postsynaptic plasma membrane. They can also
      alter the kinetics and peak amplitude of the intracellular Ca2+ responses of
      mGlu1 and mGlu5 receptors. Homer proteins can either prevent or promote
      spontaneous activation of these receptors, depending on the type of Homer protein
      isoform expressed.

PMID- 12072557
TI  - Previously uncharacterized histone acetyltransferases implicated in mammalian
      spermatogenesis.
AB  - During spermiogenesis (the maturation of spermatids into spermatozoa) in many
      vertebrate species, protamines replace histones to become the primary DNA
      packaging protein. It has long been thought that this process is facilitated by
      the hyperacetylation of histone H4. However, the responsible histone
      acetyltransferase enzymes are yet to be identified. CDY is a human Y-chromosomal
      gene family expressed exclusively in the testis and implicated in male
      infertility. Its mouse homolog Cdyl, which is autosomal, is expressed abundantly
      in the testis. Proteins encoded by CDY and its homologs bear the "chromodomain,"
      a motif implicated in chromatin binding. Here, we show that (i) human CDY and
      mouse CDYL proteins exhibit histone acetyltransferase activity in vitro, with a
      strong preference for histone H4; (ii) expression of human CDY and mouse Cdyl
      genes during spermatogenesis correlates with the occurrence of H4
      hyperacetylation; and (iii) CDY and CDYL proteins are localized to the nuclei of
      maturing spermatids where H4 hyperacetylation takes place. Taken together, these
      data link human CDY and mouse CDYL to the histone-to-protamine transition in
      mammalian spermiogenesis. This link offers a plausible mechanism to account for
      spermatogenic failure in patients bearing deletions of the CDY genes.

PMID- 12072558
TI  - Evolutionary genomics of Salmonella: gene acquisitions revealed by microarray
      analysis.
AB  - The presence of homologues of Salmonella enterica sv. Typhimurium LT2 genes was
      assessed in 22 other Salmonella including members of all seven subspecies and
      Salmonella bongori. Genomes were hybridized to a microarray of over 97% of the
      4,596 annotated ORFs in the LT2 genome. A phylogenetic tree based on homologue
      content, relative to LT2, was largely concordant with previous studies using
      sequence information from several loci. Based on the topology of this tree,
      homologues of genes in LT2 acquired by various clades were predicted including
      513 homologues acquired by the ancestor of all Salmonella, 111 acquired by S.
      enterica, 105 by diphasic Salmonella, and 216 by subspecies 1, most of which are
      of unknown function. Because this subspecies is responsible for almost all
      Salmonella infections of mammals and birds, these genes will be of particular
      interest for further mechanistic studies. Overall, a high level of gene gain,
      loss, or rapid divergence was predicted along all lineages. For example, at least
      425 close homologues of LT2 genes may have been laterally transferred into
      Salmonella and then between Salmonella lineages.

PMID- 12072559
TI  - Subcellular distribution of Wnt pathway proteins in normal and neoplastic colon.
AB  - Mutations in the APC tumor suppressor gene are present in approximately 85% of
      colorectal tumors and are thought to contribute early in the process of
      tumorigenesis. The truncated protein resulting from most APC mutations can lead
      to elevated beta-catenin levels in colon tumor cells. APC and associated proteins
      thus form a beta-catenin regulatory complex, with axin playing a key role.
      Although cell culture studies have revealed intriguing aspects of this complex,
      little characterization has been done in human colonocytes, the target tissue of
      colon carcinogenesis. The present study of intact human colon crypts, adenomatous
      polyps, and adenocarcinomas focuses on subcellular localization of some key
      elements of the complex: beta-catenin, APC, axin, and axin2. We examined
      endogenous protein localization within the framework of three-dimensional tissue
      architecture by using laser scanning confocal microscopy, and immunofluorescence
      staining of whole-mount fixed tissue from more than 50 patients. Expression
      patterns suggest that APC and axin colocalize in the nucleus and at lateral cell
      borders, and show that axin2 is limited to the nucleus. Altered nuclear
      expression of axin seen in colon polyps and carcinomas may be a consequence of
      the loss of full-length APC and the advent of nuclear beta-catenin. The
      observation of nuclear beta-catenin in fewer than half of carcinoma images and
      only rarely in polyps indicates that nuclear translocation of beta-catenin may
      not be an immediate consequence of the loss of APC.

PMID- 12072560
TI  - Adeno-associated virus type-2 expression of pigmented epithelium-derived factor
      or Kringles 1-3 of angiostatin reduce retinal neovascularization.
AB  - Neovascular diseases of the retina include age-related macular degeneration and
      diabetic retinopathy, and together they comprise the leading causes of adult
      onset blindness in developed countries. Current surgical, pharmaceutical, and
      laser therapies for age-related macular degeneration (AMD) rarely result in
      improved vision, do not significantly prevent neovascularization (NV), and often
      result in at least some vision loss. To address this therapeutic gap, we
      determined the efficacy of recombinant adeno-associated viral (rAAV) serotype-2
      mediated expression of pigment epithelium-derived factor (PEDF) or Kringle
      domains 1-3 of angiostatin (K1K3) in reducing aberrant vessel formation in a
      mouse model of ischemia-induced retinal NV. Both PEDF and K1K3 are potent
      inhibitors of NV when injected directly, hence expression of these therapeutic
      factors from rAAV may provide long-term protection from neovascular eye disease.
      rAAV vectors expressing the therapeutic gene were injected into one eye of
      postnatal day 0 (P0) newborn mouse pups. Retinal NV was induced in P7 mice by
      exposure to elevated oxygen for 5 days followed by room air for another five
      days. Retinal NV was quantified by the number of vascular-endothelial-cell nuclei
      above the inner-limiting membrane in P17 eyes. The number of such vascular
      endothelial cell nuclei in eyes treated with rAAV-PEDF or rAAV-K1K3 was
      significantly reduced (both P < 0.0000002) compared with control eyes. Ocular
      protein levels detected by ELISA correlate well with the reduction in NV and
      confirm that expression of antineovascular agents from rAAV vectors may be a
      therapeutically useful treatment of retinal or choroidal neovascular disease.

PMID- 12072561
TI  - Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to
      dilated cardiomyopathy.
AB  - The ErbB2 (Her2) proto-oncogene encodes a receptor tyrosine kinase, which is
      frequently amplified and overexpressed in human tumors. ErbB2 provides the target
      for a novel and effective antibody-based therapy (Trastuzumab/Herceptin) used for
      the treatment of mammary carcinomas. However, cardiomyopathies develop in a
      proportion of patients treated with Trastuzumab, and the incidence of such
      complications is increased by combination with standard chemotherapy. Gene
      ablation studies have previously demonstrated that the ErbB2 receptor, together
      with its coreceptor ErbB4 and the ligand Neuregulin-1, are essential for normal
      development of the heart ventricle. We use here Cre-loxP technology to mutate
      ErbB2 specifically in ventricular cardiomyocytes. Conditional mutant mice develop
      a severe dilated cardiomyopathy, with signs of cardiac dysfunction generally
      appearing by the second postnatal month. We infer that signaling from the ErbB2
      receptor, which is enriched in T-tubules in cardiomyocytes, is crucial for adult
      heart function. Conditional ErbB2 mutant mice provide a model of dilated
      cardiomyopathy. In particular, they will allow a rigorous assessment of the role
      of ErbB2 in the heart and provide insight into the molecular mechanisms that
      underlie the adverse effects of anti-ErbB2 antibodies.

PMID- 12072562
TI  - Important role of hypothalamic Y2 receptors in body weight regulation revealed in
      conditional knockout mice.
AB  - Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity
      when hypothalamic levels remain chronically elevated. To investigate the specific
      role of hypothalamic Y2 receptors in this process, we used a conditional Y2
      knockout model, using the Cre-lox system and adenoviral delivery of Cre
      recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease
      in body weight and a significant increase in food intake that was associated with
      increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic
      proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript
      (CART) in the arcuate nucleus. These hypothalamic changes persisted until at
      least 34 days after Y2 deletion, yet the effect on body weight and food intake
      subsided within this time. Plasma concentrations of pancreatic polypeptide and
      corticosterone were 3- to 5-fold increased in hypothalamus-specific Y2 knockout
      mice. Germ-line Y2 receptor knockout also produced a significant increase in
      plasma levels of pancreatic polypeptide. However, these mice differed from
      conditional knockout mice in that they showed a sustained reduction in body
      weight and adiposity associated with increased NPY and AgRP but decreased POMC
      and CART mRNA levels in the arcuate nucleus. The transience of the observed
      effects on food intake and body weight in the hypothalamus-specific Y2 knockout
      mice, and the difference of this model from germ-line Y2 knockout mice, underline
      the importance of conditional models of gene deletion, because developmental,
      secondary, or extrahypothalamic mechanisms may mask such effects in germ-line
      knockouts.

PMID- 12072563
TI  - Polynucleotide phosphorylase is a global regulator of virulence and persistency
      in Salmonella enterica.
AB  - For many pathogens, the ability to regulate their replication in host cells is a
      key element in establishing persistency. Here, we identified a single point
      mutation in the gene for polynucleotide phosphorylase (PNPase) as a factor
      affecting bacterial invasion and intracellular replication, and which determines
      the alternation between acute or persistent infection in a mouse model for
      Salmonella enterica infection. In parallel, with microarray analysis, PNPase was
      found to affect the mRNA levels of a subset of virulence genes, in particular
      those contained in Salmonella pathogenicity islands 1 and 2. The results
      demonstrate a connection between PNPase and Salmonella virulence and show that
      alterations in PNPase activity could represent a strategy for the establishment
      of persistency.

PMID- 12072564
TI  - Probing solvent accessibility of amyloid fibrils by solution NMR spectroscopy.
AB  - Amyloid is the result of an anomalous protein and peptide aggregation, leading to
      the formation of insoluble fibril deposits. At present, 18 human diseases have
      been associated with amyloid deposits-e.g., Alzheimer's disease and Prion
      transmissible Spongiform Encephalopathies. The molecular structure of amyloid is
      to a large extent unknown, because of lack of high-resolution structural
      information within the amyloid state. However, from other experimental data it
      has been established that amyloid fibrils predominantly consist of beta-strands
      arranged perpendicular to the fibril axis. Identification of residues involved in
      these secondary structural elements is therefore of vital importance to
      rationally designing appropriate inhibitors. We have designed a
      hydrogen/deuterium exchange NMR experiment that can be applied on mature amyloid
      to enable identification of the residues located inside the fibril core. Using a
      highly amyloidogenic peptide, corresponding to residues 25-35 within the
      Alzheimer Abeta(1-43) peptide, we could establish that residues 28-35 constitute
      the amyloid core, with residues 31 and 32 being the most protected. In addition,
      quantitative values for the solvent accessibility for each involved residue could
      be obtained. Based on our data, two models of peptide assembly are proposed. The
      method provides a general way to identify the core of amyloid structures and
      thereby pinpoint areas suitable for design of inhibitors.

PMID- 12072565
TI  - All intermediates of the arsenate reductase mechanism, including an
      intramolecular dynamic disulfide cascade.
AB  - The mechanism of pI258 arsenate reductase (ArsC) catalyzed arsenate reduction,
      involving its P-loop structural motif and three redox active cysteines, has been
      unraveled. All essential intermediates are visualized with x-ray crystallography,
      and NMR is used to map dynamic regions in a key disulfide intermediate. Steady
      state kinetics of ArsC mutants gives a view of the crucial residues for
      catalysis. ArsC combines a phosphatase-like nucleophilic displacement reaction
      with a unique intramolecular disulfide bond cascade. Within this cascade, the
      formation of a disulfide bond triggers a reversible "conformational switch" that
      transfers the oxidative equivalents to the surface of the protein, while
      releasing the reduced substrate.

PMID- 12072566
TI  - Hidden Markov models from molecular dynamics simulations on DNA.
AB  - An enhanced bioinformatics tool incorporating the participation of molecular
      structure as well as sequence in protein DNA recognition is proposed and tested.
      Boltzmann probability models of sequence-dependent DNA structure from all-atom
      molecular dynamics simulations were obtained and incorporated into hidden Markov
      models (HMMs) that can recognize molecular structural signals as well as sequence
      in protein-DNA binding sites on a genome. The binding of catabolite activator
      protein (CAP) to cognate DNA sequences was used as a prototype case for
      implementation and testing of the method. The results indicate that even HMMs
      based on probabilistic roll/tilt dinucleotide models of sequence-dependent DNA
      structure have some capability to discriminate between known CAP binding and
      nonbinding sites and to predict putative CAP binding sites in unknowns.
      Restricting HMMs to sequence only in regions of strong consensus in which the
      protein makes base specific contacts with the cognate DNA further improved the
      discriminatory capabilities of the HMMs. Comparison of results with controls
      based on sequence only indicates that extending the definition of consensus from
      sequence to structure improves the transferability of the HMMs, and provides
      further supportive evidence of a role for dynamical molecular structure as well
      as sequence in genomic regulatory mechanisms.

PMID- 12072567
TI  - Mutually regulated expression of Pax6 and Six3 and its implications for the Pax6
      haploinsufficient lens phenotype.
AB  - Pax6 is a key regulator of eye development in vertebrates and invertebrates, and
      heterozygous loss-of-function mutations of the mouse Pax6 gene result in the
      Small eye phenotype, in which a small lens is a constant feature. To provide an
      understanding of the mechanisms underlying this haploinsufficient phenotype, we
      evaluated in Pax6 heterozygous mice the effects of reduced Pax6 gene dosage on
      the activity of other transcription factors regulating eye formation. We found
      that Six3 expression was specifically reduced in lenses of Pax6 heterozygous
      mouse embryos. Interactions between orthologous genes from the Pax and Six
      families have been identified in Drosophila and vertebrate species, and we
      examined the control of Pax6 and Six3 gene expression in the developing mouse
      lens. Using in vitro and transgenic approaches, we found that either
      transcription factor binds regulatory sequences from the counterpart gene and
      that both genes mutually activate their expression. These studies define a
      functional relationship in the lens in which Six3 expression is dosage-dependent
      on Pax6 and where, conversely, Six3 activates Pax6. Accordingly, we show a rescue
      of the Pax6 haploinsufficient lens phenotype after lens-specific expression of
      Six3 in transgenic mice. This phenotypic rescue was accompanied by cell
      proliferation and activation of the platelet-derived growth factor alpha-R/cyclin
      D1 signaling pathway. Our findings thus provide a mechanism implicating gene
      regulatory interactions between Pax6 and Six3 in the tissue-specific defects
      found in Pax6 heterozygous mice.

PMID- 12072568
TI  - A cytosine methyltransferase homologue is essential for repeat-induced point
      mutation in Neurospora crassa.
AB  - During sexual development, Neurospora crassa inactivates genes in duplicated DNA
      segments by a hypermutation process, repeat-induced point mutation (RIP). RIP
      introduces C:G to T:A transition mutations and creates targets for subsequent DNA
      methylation in vegetative tissue. The mechanism of RIP and its relationship to
      DNA methylation are not fully understood. Mutations in DIM-2, a DNA
      methyltransferase (DMT) responsible for all known cytosine methylation in
      Neurospora, does not prevent RIP. We used RIP to disrupt a second putative DMT
      gene in the Neurospora genome and tested mutants for defects in DNA methylation
      and RIP. No effect on DNA methylation was detected in the tissues that could be
      assayed, but the mutants showed recessive defects in RIP. Duplications of the am
      and mtr genes were completely stable in crosses homozygous for the mutated
      potential DMT gene, which we call rid (RIP defective). The same duplications were
      inactivated normally in heterozygous crosses. Disruption of the rid gene did not
      noticeably affect fertility, growth, or development. In contrast, crosses
      homozygous for a mutation in a related gene in Ascobolus immersus, masc1,
      reportedly fail to develop and heterozygous crosses reduce methylation induced
      premeiotically [Malagnac, F., Wendel, B., Goyon, C., Faugeron, G., Zickler, D.,
      et al. (1997) Cell 91, 281-290]. We isolated homologues of rid from Neurospora
      tetrasperma and Neurospora intermedia to identify conserved regions. Homologues
      possess all motifs characteristic of eukaryotic DMTs and have large distinctive C
      and N-terminal domains.

PMID- 12072569
TI  - An ectopic human XIST gene can induce chromosome inactivation in
      postdifferentiation human HT-1080 cells.
AB  - It has been believed that XIST RNA requires a discrete window in early
      development to initiate the series of chromatin-remodeling events that form the
      heterochromatic inactive X chromosome. Here we investigate four adult male HT
      1080 fibrosarcoma cell lines expressing ectopic human XIST and demonstrate that
      these postdifferentiation cells can undergo chromosomal inactivation outside of
      any normal developmental context. All four clonal lines inactivated the transgene
      containing autosome to varying degrees and with variable stability. One clone in
      particular consistently localized the ectopic XIST RNA to a discrete chromosome
      territory that exhibited striking hallmarks of inactivation, including long-range
      transcriptional inactivation. Results suggest that some postdifferentiation cell
      lines are capable of de novo chromosomal inactivation; however, long-term
      retention of autosomal inactivation was less common, which suggests that
      autosomal inactivation may confer a selective disadvantage. These results have
      fundamental significance for understanding genomic programming in early
      development.

PMID- 12072570
TI  - Early experience is associated with the development of categorical
      representations for facial expressions of emotion.
AB  - A fundamental issue in human development concerns how the young infant's ability
      to recognize emotional signals is acquired through both biological programming
      and learning factors. This issue is extremely difficult to investigate because of
      the variety of sensory experiences to which humans are exposed immediately after
      birth. We examined the effects of emotional experience on emotion recognition by
      studying abused children, whose experiences violated cultural standards of care.
      We found that the aberrant social experience of abuse was associated with a
      change in children's perceptual preferences and also altered the discriminative
      abilities that influence how children categorize angry facial expressions. This
      study suggests that affective experiences can influence perceptual
      representations of basic emotions.

PMID- 12072571
TI  - Oral administration of L-arginine prevents congestive heart failure in murine
      viral myocarditis.
AB  - It was previously demonstrated that administration of the nitric oxide synthase
      inhibitor NG-nitro-l-arginine methyl ester (l-NAME) aggravated viral myocarditis
      in mice. In the current study, the effects of l-arginine, a precursor of nitric
      oxide, on congestive heart failure (CHF) in myocarditis were evaluated. Dietary l
      arginine and l-arginine plus l-NAME (l-arginine + l-NAME group) were administered
      to encephalomyocarditis virus-infected BALB/c mice over 4 weeks (experiment I)
      and to encephalomyocarditis virus-infected DBA/2 mice from the 4th through 12th
      weeks after the virus inoculation (experiment II). An infected control was
      prepared in each experiment. In experiment I, survival was higher in the l
      arginine group compared with the other two groups, and cardiac damage was less,
      as was incidence of CHF. In addition, extravasated fibrin was less prominent in
      the l-arginine group. Plasma concentrations of l-arginine and nitric oxide were
      elevated in the l-arginine group. In experiment II, plasma cardiomyopathic
      lesions in the l-arginine group were less prominent and were associated with
      lower plasma catecholamine and lower myocardial collagen concentrations compared
      with the other two groups. l-arginine treatment may be effective in preventing
      the development of CHF in viral myocarditis by modifying postmyocarditic
      architectural remodeling.

PMID- 12072572
TI  - Intrarenal detection of nitric oxide using electron spin resonance spectroscopy
      in hypertensive lipopolysaccharide-treated rats.
AB  - The inhibition of nitric oxide (NO) synthesis by chronic administration of NG
      nitro-l-arginine methyl ester (l-NAME) in rats is responsible for systemic
      hypertension. However, the mechanisms involved in this hypertension remain
      unclear. The effects of chronic l-NAME on kidney and blood NO production were
      studied in rats in a state of endotoxic shock due to lipopolysaccharide (LPS). A
      nitric oxide spin trapping technique using electron spin resonance (ESR)
      spectroscopy has been used to identify and measure the production of NO in the
      kidney. This method is based on the trapping of nitric oxide by a metal-chelator
      complex consisting of N-methyl-d-glucamine dithiocarbamate (MGD) and reduced iron
      (Fe2+) forming a water-soluble NO-FeMGD complex detected by ESR. After LPS
      injection (14 mg/kg, IV, 6 h before the sacrifice) to rats pretreated with l-NAME
      (10 mg/kg/d over 14 days), the NO-FeMGD complex was evaluated in the kidney
      (arbitrary units [AU]/g of kidney) and the density of polynuclear neutrophils was
      counted by light microscopy. Chronic inhibition of NO synthase by l-NAME, a
      nonspecific inhibitor, was responsible for a decrease of the NO-FeMGD complex
      levels in the kidney (24.9 +/- 1.6 AU versus 13.8 +/- 1.3 AU). LPS administration
      was responsible for a large increase in both NO-FeMGD complex and neutrophil
      levels in the kidney of normotensive rats (332.6 +/- 12.8 AU versus 24.9 +/- 1.6
      AU for NO-FeMGD complex and 1.36 +/- 0.41 versus 0.11 +/- 0.03 for neutrophils).
      Conversely, LPS administration in hypertensive, l-NAME-pretreated rats was linked
      to a smaller increase in the NO-FeMGD complex (85.1 +/- 7.9 AU versus 332.6 +/-
      12.8 AU) and a larger increase in glomerular neutrophils (2.48 +/- 0.36 versus
      1.36 +/- 0.41) compared with normotensive rats. These results are in agreement
      with a direct implication of NO during LPS-and l-NAME-induced kidney injuries.

PMID- 12072573
TI  - Endothelin-induced myoplasmic Ca2+ responses and tyrosine phosphorylation in
      coronary smooth muscle.
AB  - This study investigated the role of tyrosine phosphorylation and source of Ca2+
      in prolonged endothelin-1 (ET-1)-induced potentiation of myoplasmic free Ca2+
      ([Ca2+]m) responses to depolarization in coronary smooth muscle cells. Fura-2
      microfluorometry showed typical increases in [Ca2+]m in response to 80 mM K+
      (80K) and 0.01 microM endothelin. After washout of ET-1 80K-induced [Ca2+]m
      increases were augmented (potentiated) 31%. Time to peak [Ca2+]m response to 80K
      was less after ET-1 exposure than before. ET-1 potentiation of 80K-induced
      [Ca2+]m responses by decreased sarcoplasmic reticulum (SR) buffering of [Ca2+]m
      or Ca2+-induced Ca2+ release was ruled out by lack of potentiation by 5 mM
      caffeine and 1 microM thapsigargin. Diltiazem abolished potentiation, providing
      evidence for Ca2+ influx through voltage-gated Ca2+ channels (VGCC). Genistein
      (30 microM) and methyl 2,5-dihydroxycinnamate (1 microM, MDHC) abolished
      potentiation of Ca2+ influx. Single cell phosphotyrosine measured directly by
      immunofluorescence was increased 95% in cells treated with ET-1 compared to
      control, genistein, and MDHC treated cells. ET-1 increased tyrosine
      phosphorylation of an 80-85 kDa protein, but not the 240 kDa alpha1C subunit of
      the VGCC. Tyrosine phosphorylation of proteins other than VGCC is necessary for
      prolonged potentiation by ET-1 of depolarization-induced Ca2+ influx.

PMID- 12072574
TI  - Valsartan therapy has additive anti-oxidative effect to that of fluvastatin
      therapy against low-density lipoprotein oxidation: studies in
      hypercholesterolemic and hypertensive patients.
AB  - In hypercholesterolemic and hypertensive patients, an increased propensity of
      their low-density lipoprotein (LDL) to oxidative modification has been observed.
      Because oxidized LDL (ox-LDL) plays a major role in atherosclerosis, the current
      study analyzed the anti-oxidative effect of valsartan (an angiotensin II receptor
      antagonist) therapy in combination with fluvastatin therapy in these patients.
      Administration of 40 mg/d of fluvastatin for 2 months to seven patients resulted
      in significant reduction in plasma total and LDL cholesterol (by 24-28%).
      Valsartan administration (80 mg/d for an additional 2-month period) in
      combination with fluvastatin did not further affect plasma cholesterol levels.
      Fluvastatin therapy inhibited the susceptibility of LDL to copper ion-induced
      oxidation, as shown by prolongation of the lag time by 22% and by a reduction of
      thiobarbituric acid-reactive substances (TBARS) levels by 14%, as compared with
      the patient's LDL baseline oxidation. The addition of valsartan to fluvastatin
      resulted in a further 17% prolongation of the lag time and in an additional
      reduction of 21% in TBARS levels. In a parallel study, the LDL from eight
      patients who were first treated with 80 mg/d of valsartan for 2 months
      demonstrated reduced susceptibility to copper ion-induced oxidation, as observed
      by prolongation of lag time by 23% and reduction in TBARS levels by 19%, compared
      with the baseline values. The administration of 40 mg/d of fluvastatin for an
      additional 2 months in combination with valsartan, however, demonstrated no
      further inhibitory effect on LDL oxidation. The anti-oxidative properties of
      fluvastatin and valsartan against LDL oxidation were also demonstrated in vitro
      and the combination of both drugs was shown to have an additive effect. Valsartan
      therapy in hypercholesterolemic and hypertensive patients has an additive anti
      oxidative effect to that of fluvastatin therapy. This may be related both to the
      anti-oxidative properties of valsartan and to the blocking of angiotensin II
      induced oxidative stress.

PMID- 12072575
TI  - D2 -like receptor stimulation decreases effective renal plasma flow and
      glomerular filtration rate in spontaneously hypertensive rats.
AB  - In spontaneously hypertensive rats (SHRs) the dopaminergic D1-like renal
      vasodilator response is impaired. The renal vascular response to D2-like receptor
      stimulation in vivo is incompletely known. Therefore, renal hemodynamics were
      studied in conscious SHRs during continuous infusion of D2-like agonist N,N-Di-n
      propyldopamine (DPDA) (10 microg/kg/min) with Wistar-Kyoto (WKY) rats as
      controls. As sodium status may affect dopaminergic responses, rats were studied
      during both low- and high-sodium diets. D2-like stimulation reduced mean arterial
      pressure and effective renal plasma flow and glomerular filtration rate (GFR)
      similarly in SHR and WKY rats. Renal vascular resistance increased significantly
      in both strains. The response to DPDA is modified by sodium status, with a more
      pronounced fall in blood pressure (in WKYs and SHRs) and GFR (in WKYs) during
      high-sodium conditions. The responses were blocked by co-infusion with D2
      antagonist domperidone. Thus, D2-like renal vascular responses are normal in SHRs
      irrespective of sodium intake. The combination of a preserved D2-like renal
      vasoconstrictive and an impaired D1-like renal vasodilatory response may
      contribute to maintenance of hypertension in SHRs.

PMID- 12072576
TI  - Involvement of K+ channels in adenosine A2A and A2B receptor-mediated
      hyperpolarization of porcine coronary artery endothelial cells.
AB  - This study investigated the effects of the following adenosine agonists: 5;
      ethylcarboxamidoadenosine (NECA), N6-cyclopentyadenosine (CPA) 2-[p-(2
      carboxyethyl)]phenylamino-5;N-ethylcarboxamidoadenosine (CGS-21680), and 2
      chloroadenosine (CAD) and its antagonist, 4-(2-[7-amino-2-[2-furyl]]1,2,4
      triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-241385), a selective A2A
      adenosine receptor antagonist, and the involvement of the K+ATP and KCa channels
      on the resting membrane potential (RMP) of confluent monolayers of cultured
      porcine coronary artery endothelial cells (PCAECs). Adenosine agonists and K+ATP
      channel openers (pinacidil, cromakalim) hyperpolarized cultured PCAECs. The
      average RMP was -32.31 +/- 1.2 mV. Adenosine agonists at 10-5 M caused a
      significant increase in RMP to -65.0 +/- 1.5 mV for CAD (a nonselective adenosine
      receptor agonist) to -75.9 +/- 1.6 mV for CGS-21680 (a selective A2A receptor
      agonist) and to -87.0 +/- 3.5 mV for NECA (a nonselective A1/A2A/A2B receptor
      agonist). Pinacidil and cromakalim at 10 microM increased the membrane potential
      to -76.2 +/- 1.2 mV and -75.22 +/- 0.12 mV, respectively. The hyperpolarization
      induced by adenosine receptor agonists and KATP openers was inhibited by an
      application of the K+ATP channel blocker glibenclamide (10 microM), indicating
      the involvement of the K+ATP channel in the adenosine-mediated hyperpolarization
      of PCAECs. Moreover, 1-EB10, a selective opener of the maxi-KCa channel,
      hyperpolarized PCAECs, and the effect of 1-EB10 was completely blocked by a
      selective, irreversible blocker of the high conductance KCa (maxi-K) channels
      (penitrem A), but it only partially blocked the effect of NECA. ZM-241385 has no
      effect on hyperpolarization elicited by K+ATP and KCa channel openers. However,
      ZM-241385 significantly blocked the hyperpolarization effect of CAD and CGS
      21680. ZM-241385 partially blocked the hyperpolarizing effect of NECA, and a
      combination of ZM-241385 and penitrem A further blocked the hyperpolarizing
      effect of NECA. These results further support the involvement of K+ channels in
      adenosine A2A and A2B receptor-mediated hyperpolarization of PCAECs.

PMID- 12072577
TI  - Prejunctional and postjunctional inhibitory actions of eprosartan and candesartan
      in the isolated rabbit mesenteric artery.
AB  - Effects of angiotensin II type 1 (AT1) receptor antagonists eprosartan and
      candesartan and AT2 receptor antagonist PD123319 on Ang II-induced facilitation
      of noradrenergic neurotransmission were investigated in isolated rabbit
      mesenteric artery under isometric conditions. Sympathoinhibitory potency of AT1
      blockers was compared with their potency concerning inhibition of direct
      vasoconstrictor effect of Ang II. To investigate blockade of presynaptic AT1 and
      AT2 receptors, effects of Ang II on electrical field stimulation (EFS)-induced
      contractions in presence or absence of eprosartan, candesartan, or PD123319 were
      studied. To investigate blockade of postsynaptic AT1 receptors, effects of either
      eprosartan or candesartan on concentration-response curves of Ang II were
      studied. In addition, effect of Ang II on postsynaptic alpha-adrenoceptor
      mediated responses was studied using noradrenaline. EFS (1, 2, and 4 Hz) caused
      an increase of contractile force. At stimulation frequencies of 1, 2, and 4 Hz, a
      subpressor concentration of Ang II (0.5 nM) increased stimulation-induced
      vasoconstrictor responses by 2.8 +/- 0.5, 2.4 +/- 0.4, and 1.6 +/- 0.1 of control
      values, respectively (p < 0.05 compared with control for all frequencies). The
      enhancement could be antagonized by eprosartan (1 nM-0.1 microM) and candesartan
      (1 nM-0.1 microM). The AT2 antagonist PD123319 (10 nM) did not influence Ang II
      induced facilitation of stimulation-induced contractions. Contractile responses
      to exogenous noradrenaline were unaltered in presence of Ang II 0.5 nM. Ang II (1
      nM-0.3 microM) caused a concentration-dependent increase in contractile force,
      which could be antagonized by eprosartan (pD2; 8.8 +/- 0.19) and candesartan
      (pD2; 11.3 +/- 0.23). Thus, the facilitating effect of Ang II on noradrenergic
      neurotransmission is mediated by presynaptically located AT1 receptors and not by
      AT2 receptors. For eprosartan, sympathoinhibition was achieved at concentrations
      that also block AT1 receptors on vascular smooth muscle. In contrast, for
      candesartan, presynaptic inhibitory concentrations were considerably higher than
      those required for postsynaptic inhibition.

PMID- 12072578
TI  - Physiologic increases in extracellular sodium salt enhance coronary
      vasoconstriction and Ca2+ entry.
AB  - High dietary sodium salt has been suggested to increase the risk of coronary
      vasospasm and coronary artery disease. However, whether high-sodium salt directly
      affects the mechanisms of coronary artery contraction is unclear. This study
      investigated whether physiologic and supraphysiologic increases in extracellular
      concentrations of sodium chloride ([NaCl]e) enhance the Ca2+ handling mechanisms
      of coronary smooth muscle contraction. Isometric contraction and 45Ca2+ influx
      were measured in endothelium-denuded porcine coronary artery strips incubated in
      Krebs solution (2.5 mM Ca2+) containing increasing [NaCl]e (120, 121, 123, 126,
      130, 140, and 150 mM). Increasing [NaCl]e for 30 min did not increase the resting
      coronary tone or 45Ca2+ influx. 5-Hydroxytryptamine (5-HT) caused concentration
      dependent increases in contraction and 45Ca2+ influx. Preincubation of coronary
      strips in increasing [NaCl]e for 30 min did not change the median effective dose
      of 5-HT. However, the magnitude of the 5-HT contraction and 45Ca2+ influx was
      significantly increased at 121-126 mM [NaCl]e. Preincubation with 2,4
      dichlorobenzamil (10-5 M), inhibitor of the Na+/Ca2+ exchanger, or KB-R7943 (10-5
      M), selective inhibitor of the reverse mode of the Na+/Ca2+ exchanger, abolished
      the increases in 5-HT contraction and 45Ca2+ influx at 121-126 mM [NaCl]e.
      Preincubation in Krebs solution containing 120 mM NaCl plus 1-6 mM LiCl or N
      methyl-d-glucamine did not increase 5-HT contraction or 45Ca2+ influx. Higher
      [NaCl]e (140-150 mM) increased 5-HT-induced 45Ca2+ influx but inhibited 5-HT
      contraction. 5-HT (10-5 M)- and caffeine (25 mM)-induced contraction in Ca2+-free
      (2 mM EGTA) solution, a measure of Ca2+ release from the intracellular stores,
      was not affected by small increases in [NaCl]e (121-126 mM) but was inhibited at
      higher [NaCl]e (130-150 mM). Thus increases in [NaCl]e within the physiologic
      range enhance coronary smooth muscle contraction to 5-HT by a mechanism possibly
      involving Ca2+ entry via the reverse mode of the Na+/Ca2+ exchanger, but not Ca2+
      release from the intracellular stores. The reduction of coronary contraction with
      supraphysiologic [NaCl]e in both Ca2+-containing and Ca2+-free Krebs could be
      related to excessive increases in ionic strength and may mask significant
      coronary vasoconstrictor effects of physiologic increases in [NaCl]e.

PMID- 12072579
TI  - Long-term low-dose treatment with reserpine of cholesterol-fed rabbits reduces
      cholesterol in plasma, non-high density lipoproteins and arterial walls.
AB  - The effects of long-term low-dose treatment with reserpine on plasma lipoproteins
      and arterial cholesterol were determined in cholesterol-fed rabbits. Hepatic low
      density lipoprotein (LDL) receptors; uptake of LDL by liver, heart, and kidneys;
      plasma fibrinogen; blood pressure; and heart rate were also determined. Reserpine
      at 43 microg/kg. d was continuously infused subcutaneously via implanted
      minipumps for 6 weeks into conscious unrestrained male New Zealand White rabbits
      (n = 5) fed a 0.2% cholesterol-enriched diet. Compared with controls, reserpine
      (n = 4) significantly reduced the elevated levels of plasma total cholesterol and
      esterified and unesterified cholesterol throughout the study, and at 6 weeks of
      treatment these reductions were 42, 41, and 49%, respectively. The increased
      cholesterol in the aortic walls (n = 5) produced by the atherogenic diet was
      reduced by 73% (p < 0.004) and 125I-tyramine cellobiose-labeled LDL by 67 to 86%
      (0.05 < p <0.004), respectively. The aortic intimal-medial thickness ratio was
      reduced by 70%. The decrease in elevated plasma total cholesterol was mainly due
      to cholesterol reductions in both LDL (41%) and non-high density lipoprotein
      (HDL) of density < 1.019 g/ml (51%). HDL cholesterol and triglyceride levels were
      unchanged. Reserpine had no significant effects on the clearance of 125I-tyramine
      cellobiose-LDL from plasma and there was a trend towards an increase in hepatic
      LDL receptor expression. Heart rate was decreased by 28%. There were no
      significant effects on blood pressure, liver and heart lipids, hematocrit, or
      plasma fibrinogen. The results suggest that treatment of cholesterol-fed rabbits
      with reserpine at a low dose over a long period prevents increases in plasma
      atherogenic lipoproteins. Reserpine decreases the cholesterol in aortic walls and
      the intima-media thickness ratio. This anti-atherosclerotic effect of reserpine
      may have therapeutic implication.

PMID- 12072580
TI  - Endothelin 1-induced pressor response and vasopressin release in rats with heart
      failure.
AB  - Heart failure (HF) is characterized by activation of both neurohumoral and
      sympathetic nervous systems. Specifically, HF is associated with increases in
      vasopressin (VP) and endothelin (ET) and in arterial baroreflex dysfunction.
      Hypothesis was that central ET-1 potentiates VP secretion in HF due to impaired
      pressor response and diminished arterial baroreflex inhibition. Male Sprague
      Dawley rats were studied 42 to 54 days after sham or coronary ligation (HF) and 7
      days after sinoaortic denervation (SAD). Conscious rats received
      intracerebroventricular artificial cerebrospinal fluid (CSF), 10 pmol of ET-1, 40
      nmol BQ123, or both. Basal mean arterial pressure (MAP) did not differ, but heart
      rate and left ventricular end-diastolic pressure were significantly higher in HF
      and HF/SAD. Baseline VP was higher in both HF and HF/SAD: 5.9 +/- 0.4 pg/ml and
      5.6 +/- 0.7 pg/ml versus sham 2.8 +/- 0.2 and sham-SAD 1.6 +/- 0.2 (p < 0.001).
      ET-1 increased MAP in sham rats by 16.0 +/- 1.4 mm Hg, but only by 7.4 +/- 2.2 mm
      Hg in HF (p < 0.05 versus sham) and 5.8 +/- 2.4 mm Hg in HF/SAD (p < 0.01 versus
      sham SAD). Tachycardic response was attenuated in HF/SAD compared with HF alone.
      After ET-1, VP increased by 3.3 +/- 2.7 pg/ml in sham and 13.3 +/- 2.6 pg/ml in
      HF (p < 0.05), but only by 2.3 +/- 0.7 pg/ml in HF/SAD (p < 0.01 versus HF).
      BQ123 blocked all responses to exogenous ET-1 but had no effect on baseline
      values. Thus, ET-evoked a lower pressor response in HF due to an impaired ability
      to increase heart rate and cardiac output. ET-1-induced VP release in HF was
      higher than in controls as a result of lower pressor response or impaired
      arterial baroreflex. In contrast to rats with normal left ventricular function,
      sinoaortic denervation in HF failed to potentiate either pressor response or VP
      secretion. These findings suggest that acute, though modest, increases in
      afterload may increase left atrial pressure more in HF/SAD such that
      cardiopulmonary reflexes may be activated or natriuretic peptides may be released
      that further restrain both pressor and VP responses.

PMID- 12072581
TI  - Aldosterone modulates the effect of angiotensin II on the electrical properties
      of rat heart.
AB  - Influence of aldosterone on the effect of angiotensin II on action potential
      duration and cardiac refractoriness was investigated in isolated ventricle of
      adult rats treated with aldosterone (2 microM/kg/d, intraperitoneally) for 48 h.
      Results indicated that angiotensin II (10-8 M) increases action potential
      duration at 50 and 90% of repolarization by 33 +/- 8.3% and 76 +/- 6.5% (p <
      0.05), respectively (p < 0.05). Cardiac refractoriness and rheobase were
      increased by the peptide. These results contrast with those found in controls in
      which angiotensin II (10-8 M) reduces action potential duration at 50 and 90% of
      repolarization by 31.8 +/- 3.7% and 23 +/- 4.1% (p < 0.05), respectively, and
      decreases refractoriness. The increase in cardiac refractoriness elicited by
      angiotensin II on rats treated with aldosterone was reversed by verapamil (10-6
      M) added to the bath. Moreover, verapamil significantly reduced the increment in
      action potential duration, at 90% repolarization, elicited by the peptide in
      presence of aldosterone, which suggests than an increase in inward calcium
      current is involved in the effect of angiotensin II. Aldosterone, however, did
      not influence effect of isoproterenol on action potential duration and
      refractoriness. Aldosterone modulates effect of angiotensin II on electrical
      properties of the heart. These findings indicate that effect of angiotensin II on
      electrical and probably other properties of the heart must be evaluated
      considering the presence or absence of aldosterone.

PMID- 12072582
TI  - Role of nitric oxide synthase, cytochrome P-450, and cyclooxygenase in the
      inotropic and lusitropic cardiac response to increased coronary perfusion.
AB  - Although studies have reported that increase in coronary perfusion (CP) results
      in positive inotropic effects, the underlying mechanisms of these actions and
      possible alterations in myocardial diastolic function are not well defined.
      Hypothesis was that nitric oxide (NO) and derivatives of cytochrome (CYT) P-450
      or cyclooxygenase (COX) might contribute to interplay between coronary and
      myocardial compartments in these conditions. Using isovolumically contracting,
      isolated perfused hamster heart model, coronary flow (CF) was increased
      mechanically, stepwise in the physiologic range (+2 to +10 ml/min), before and
      after inhibition of NO synthase by NG-nitro-l-arginine methyl ester (l-NAME) (30
      microM), CYT P-450 by SKF525A (1 microM), or COX by indomethacin (10 microM). CP
      pressure, left ventricular systolic pressure (VSP) and ventricular diastolic
      pressure (VDP), and heart rate (HR) were monitored continuously during the
      experiments. Mechanical increases in CF resulted in gradual change in CP pressure
      (+20% to +100%), left VSP (+5% to +40%) and VDP (+2% to +25%), whereas HR was not
      affected. In presence of l-NAME, the positive inotropic response and negative
      lusitropic effect of CF changes were similar. Exposure to SKF525A did not modify
      cardiac response to mechanical increases in CF. In presence of COX inhibitor
      indomethacin, left VSP rose to a level similar to that observed in control
      conditions, whereas VDP deteriorated further. These results suggest that
      mediators originating from NO synthase, CYT P-450, or COX do not contribute to
      positive inotropic response elicited by increased CP. However, COX derivatives
      seem to attenuate impairment of myocardial relaxation observed in these
      conditions. Such findings may have implications in development of therapeutics
      for patients with myocardial diastolic dysfunction.

PMID- 12072583
TI  - Amiloride and KB-R7943 in outward Na+ /Ca2+ exchange current in guinea pig
      ventricular myocytes.
AB  - The reverse mode of Na+/Ca2+ exchange represents an important pathway in inducing
      Ca2+ overload during ischemia and reperfusion. The inhibitory effects of
      amiloride and KB-R7943 on Na+/Ca2+ exchange current (INa/Ca) were investigated in
      guinea pig ventricular myocytes. Whole-cell patch clamp techniques were used
      under bidirectional ionic conditions and 25 mM of Na+ in pipette solution. At +50
      mV, amiloride 10, 30, and 100 microM inhibited the outward INa/Ca by 15, 23, and
      41%, respectively; at -80 mV, it inhibited inward INa/Ca by 6, 15, and 23%,
      respectively. Its inhibitory effect on outward INa/Ca was greater than that on
      inward INa/Ca. At +50 mV, KB-R7943 1 and 10 microM inhibited the outward INa/Ca
      by 29 and 61%, respectively; at -80 mV, it inhibited inward INa/Ca by 22 and 57%,
      respectively. KB-R7943 inhibited both directions of the exchange current with an
      equal potency. The data suggest that KB-R7943 is not a selective inhibitor on
      reverse mode of Na+/Ca2+ exchange.

PMID- 12072584
TI  - Pharmacokinetics of irbesartan are not altered in special populations.
AB  - Studies were conducted to determine whether pharmacokinetics of irbesartan
      (IRBE), a potent, long-acting angiotensin (AT)-II receptor antagonist selective
      for AT-II type 1 receptor subtype, are altered in patients with renal impairment
      (RI), hepatic impairment (HI), or heart failure (HF) or by patient gender, age,
      or race. IRBE pharmacokinetics and blood pressure (BP) response in hypertensive
      (HT) children and adolescents were also studied. HI or RI (including end-stage
      renal disease requiring hemodialysis) had no effect on IRBE pharmacokinetics
      after single or repeated dosing. IRBE was not removed by hemodialysis. In
      patients with New York Heart Association class II or III HF, IRBE single-dose
      pharmacokinetics were not altered following either oral or IV administration.
      There were no clinically significant differences in IRBE pharmacokinetics between
      men and women, elderly and young, or black and white patients. No accumulation of
      IRBE occurred with repeated dosing in RI or HI patients or in HT men or women. In
      a pediatric study, IRBE pharmacokinetics were comparable between 6- to 12-year
      and 13- to 16-year age groups and to that previously determined for adult
      subjects receiving the same dose; accumulation of IRBE was minimal during
      multiple dosing. IRBE lowered BP in the pediatric population. Adverse event
      profile with IRBE was similar in all patient groups. Based on these
      pharmacokinetic and safety data, no dosage adjustments of IRBE are necessary for
      patients with RI, HI, or HF, or based on patient age, gender, or race. IRBE may
      be a treatment option for pediatric HT patients. The pharmacokinetic profile of
      IRBE and lack of necessary dosage adjustments in special populations suggest that
      IRBE is an excellent choice for management of hypertension across all patient
      groups.

PMID- 12072585
TI  - Tyrosine kinase inhibition attenuates vasopressin-induced contraction of
      mesenteric resistance arteries: alterations in spontaneously hypertensive rats.
AB  - This study examined the role of tyrosine kinase-dependent signaling pathways in
      arginine vasopressin (AVP)-induced contractile responses in resistance arteries
      from spontaneously hypertensive rats (SHR). Systolic blood pressure was measured
      in conscious 6- and 21-week old SHR and Wistar Kyoto rats (WKY) by tail cuff
      measurements. Segments of third-order mesenteric arteries (about 200 microm in
      diameter, 2mm in length) were mounted in a pressurized chamber with the
      intraluminal pressure maintained at 45 mmHg. Contractile effects of AVP (10-12 to
      10-7 mol/l) were determined in the absence and presence of the selective tyrosine
      kinase inhibitor tyrphostin A23 (10-5 mol/l) and the inactive analogue,
      tyrphostin A1 (10-5 mol/l). Systolic blood pressure was significantly higher in
      SHR compared with age-matched WKY (p < 0.01). AVP increased contraction in a dose
      dependent manner with significantly greater responses in adult SHR (pD2 = 10.3 +/
      0.06) than age-matched WKY (pD2 = 9.4 +/- 0.04). Tyrphostin A23 shifted the AVP
      dose response curve to the right in 6- and 21-week WKY and 6-week SHR, but had
      little effect on AVP-induced responses in 21-week-old SHR. Tyrphostin A1 did not
      influence contraction in any groups. Protein tyrosine phosphorylation in VSMCs
      and mesenteric arteries was increased 2-3 fold in 21-week SHR compared with WKY
      counterparts. AVP significantly increased tyrosine phosphorylation in VSMCs, with
      enhanced effects in SHR compared with WKY (p < 0.05). These effects were
      inhibited by tyrphostin A23. Our findings demonstrate that protein tyrosine
      kinases contribute to AVP-induced contraction of resistance arteries from WKY and
      SHR during the phase of developing hypertension. These processes do not seem to
      play an important role in AVP-induced hypercontractility in SHR with established
      hypertension.

PMID- 12072586
TI  - Lercanidipine in type II diabetic patients with mild to moderate arterial
      hypertension.
AB  - This study evaluates the effects of lercanidipine antihypertensive treatment on
      glucose homeostasis in patients with type II diabetes mellitus with mild to
      moderate hypertension. Forty patients were enrolled. After a 2-week wash-out
      period, they were randomly allocated to receive in double-blind manner either 10
      mg or 20 mg in single daily administration for 8 weeks. Nonresponding patients
      after the initial 4 weeks, were titrated up to 20 mg and 30 mg lercanidipine,
      respectively. At the end of the double-blind treatment, all patients entered in
      single-blind 4 weeks placebo follow-up. Systolic and diastolic blood pressure
      significantly decreased in both groups of patients after 4 weeks of treatment,
      and decreased further during the following 4 weeks. In both groups, progressive
      and significant decrease in fasting blood glucose, glycosylated hemoglobin and
      area under the curve of the oral glucose tolerance test were detected during
      lercanidipine treatment. Similarly, a decrease in serum fructosamine values were
      also observed. All variables returned to towards baseline values during the
      placebo follow-up period. Adverse events (headache and mild asthenia) were
      limited to two patients and resolved spontaneously. These data indicate that
      lercanidipine is effective in lowering high blood pressure in hypertensive
      patients with type II diabetes mellitus and does not exert negative effects on
      glucose homeostasis.

PMID- 12072588
TI  - Nifedipine prevents apoptosis of endothelial cells induced by oxidized low
      density lipoproteins.
AB  - Calcium channel blockade has been shown to inhibit experimental atherosclerosis,
      and early clinical trials suggest that it also reduces atherosclerosis in humans.
      However, the mechanisms underlying the direct protective effect of calcium
      channel blockade on endothelial cell injury are not fully understood. The
      apoptosis of endothelial cells induced by oxidized low-density lipoproteins
      (oxLDL) may provide a mechanistic clue to the "response-to-injury" hypothesis of
      atherogenesis. Here we report that the calcium channel blocker, nifedipine,
      prevents the apoptosis of human umbilical venous endothelial cells (HUVECs)
      induced by oxLDL via downregulation of the endothelial receptor for oxidized LDL
      (LOX-1) and inhibition of CPP32-like protease activity. The incubation of HUVEC
      with oxLDL increased LOX-1 mRNA levels and CPP32-like protease activity, and
      induced apoptosis. Preincubation of HUVEC with nifedipine before incubation with
      oxLDL significantly suppressed the increase in LOX-1 mRNA levels and CPP32-like
      protease activity, preventing apoptosis in a dose-dependent manner. These results
      suggest that nifedipine blocks the suicide pathway leading to the apoptosis of
      endothelial cells by decreasing LOX-1 mRNA levels and CPP32-like protease
      activity. Thus, nifedipine seems to play a protective role against the "response
      to-injury" hypothesis of atherogenesis.

PMID- 12072587
TI  - Chronically inhaled salmeterol improves pulmonary function in heart failure.
AB  - Inhaled beta-agonists are commonly prescribed for the symptoms of exercise
      intolerance in heart failure despite a paucity of data regarding their safety and
      efficacy. This was a prospective, randomized, double-blind, double-dummy, placebo
      controlled 14-day cross-over study to determine if chronic inhaled salmeterol
      therapy 84 microg every 12 hours improved pulmonary function without augmentation
      of neurohormonal systems or ventricular ectopy in 8 symptomatic heart failure
      subjects with left ventricular ejection fraction (LVEF) <40% and FEV1 <or=80%.
      The primary endpoint was FEV1, and the secondary endpoints were forced vital
      capacity (FVC), forced expiratory flow (FEF25-75), peak expiratory flow rate
      (PEFR), blood pressure, heart rate, rate-pressure product, plasma norepinephrine,
      plasma epinephrine, plasma renin activity, percent ventricular ectopy, and
      salmeterol pharmacokinetics. Salmeterol was associated with a significant 6%
      improvement in FEV1 compared with placebo (salmeterol 2.46 +/- 0.73 vs. placebo
      2.33 +/- 0.73 L, p = 0.01). There was no significant difference in FVC, FEF25-75,
      and PEFR. Salmeterol increased mean rate-pressure product by 5% (salmeterol 8878
      +/- 1560 vs. placebo 8414 +/- 1440 bpm x mm Hg, p = 0.04), although no increase
      in plasma norepinephrine, epinephrine, plasma renin activity or ventricular
      ectopy was detected. The Tmax, Cmax, and half-life of salmeterol at steady-state
      were 5 min, 715 pg/ml and 11.4 hours, respectively. Inhaled salmeterol
      significantly improves FEV1 without producing measurable effects on
      neuroactivation or ventricular ectopy. Inhaled salmeterol causes minor increases
      in rate-pressure product, whose clinical significance remains to be determined.
      The plasma half-life of salmeterol may be prolonged in heart failure patients,
      thus leading to accumulation at steady-state.

PMID- 12072589
TI  - Relaxant effects of selective phosphodiesterase inhibitors on U46619
      precontracted human intralobar pulmonary arteries and role of potassium channels.
AB  - We examined the influence of K+ channel antagonists on the vasorelaxation induced
      by theophylline (non selective PDEI), siguazodan (PDE3I), rolipram (PDE4I) and
      zaprinast (PDE5I) in human intralobar pulmonary arteries. All PDEI tested induced
      a concentration-dependent relaxation with theophylline being significantly (p <
      0.05) more efficient and rolipram more potent than PDE5I and PDE3I (Emax values,
      expressed as a percentage of maximal relaxation by papaverine 10(-4)M, were 92%
      +/- 2%, 84% +/- 8%, 90% +/- 4% and 99% +/- 1%, and pD2 values were 7.30 +/- 0.35,
      6.14 +/- 0.25, 5.86 +/- 0.17, and 4.85 +/- 0.47 for rolipram, siguazodan,
      zaprinast and theophylline, respectively). 4-Aminopyridine (4-AP, Kv, voltage
      dependent channel blocker, 1 mM) induced a significant increase (+17% p < 0.05)
      of U46619-induced vasoconstriction whereas the other K+-channels blockers,
      glibenclamide (KATP channels, 1 microM) charybdotoxin (predominant BKCa, large
      conductance Ca2+-sensitive K+ channels, 0.1 microM) and apamine (SKCa, small
      conductance, 0.3 microM) were without effect. The concentration response curves
      (CRC) for rolipram were significantly shifted to the right by glibenclamide (1
      microM), charybdotoxin (0.1 microM) and 4-AP (1 mM). The CRC for siguazodan was
      significantly displaced to the right by 4-AP. None of the potassium channel
      blockers displaced the CRC for zaprinast and theophylline. Apamine was without
      effect on the CRC for all the PDEI used in this study. (1) PDE3, 4 and 5 are
      functionally present in human intralobar pulmonary arteries; (2) the
      vasoconstriction induced by U46619 is downregulated by 4-aminopyridine sensitive
      K+ channels; (3) the relaxant effects of rolipram (PDE4I) are partly mediated
      through KATP, BKCa, and Kv potassium channels and those of siguazodan (PDE3I) by
      Kv potassium channels.

PMID- 12072590
TI  - Can biochemical markers be used to screen patients with inflammatory bowel
      disease for osteoporosis?
AB  - Reduced bone mineral density has been reported in patients with inflammatory
      bowel disease and recent studies indicate that there is also an increase in the
      relative risk of fracture. Absolute risk of fracture is, however, generally low
      and thus measurement of bone mineral density as a screening procedure for all
      patients with inflammatory bowel disease may be inappropriate. In one study,
      urinary excretion of N-telopeptides, which reflects whole body bone resorption,
      was shown to be negatively related to bone mineral density, raising the
      possibility that this measurement could be used to select those in whom bone
      densitometry is required. However, the value of this approach in predicting
      fracture risk remains unproven and the relative contributions of clinical risk
      factors, biochemical markers of bone turnover and bone mineral density
      measurements to fracture risk in patients with inflammatory bowel disease require
      further study.

PMID- 12072591
TI  - Secondary prophylaxis of oesophageal variceal haemorrhage: a role for
      transjugular intrahepatic portosystemic shunt?
AB  - Cirrhotic patients who survive an episode of acute variceal haemorrhage are at
      high risk of recurrent bleeding. Many treatments have been found to be effective
      at preventing rebleeding, including drug therapy, endoscopic treatments and
      transjugular intrahepatic portosystemic stunt (TIPS). In this issue of European
      Journal of Gastroenterology & Hepatology, Jalan et al. compared three historical
      cohorts of patients with cirrhosis after index variceal bleed and found a lower
      rebleeding rate in patients receiving TIPS (16.2%) compared to either band
      ligation (39.3%) or endoscopic variceal sclerotherapy (74.6%). Despite the
      efficacy of TIPS in preventing variceal rebleeding, there was no significant
      difference in survival between the three cohorts. However, sub-group analysis
      found a lower mortality in patients with Child-Pugh class C cirrhosis receiving
      TIPS. Unfortunately, this promising observation in patients with advanced
      cirrhosis is not supported by the results of meta-analysis of randomized studies.
      Therefore, we do not recommend TIPS as first-line therapy to prevent variceal
      rebleeding in patients with cirrhosis.

PMID- 12072592
TI  - Success in treating mild chronic hepatitis C: different outcomes -- new
      guidelines?
AB  - Limited knowledge of the natural history of chronic hepatitis C suggests that
      patients with mild histological changes on liver biopsy are at low risk of
      developing liver related morbidity or mortality. Patients with mild disease have
      been excluded from the large trials of treatment for hepatitis C and consequently
      guidelines recommend that they are excluded from treatment. However, as the
      probability of a beneficial response to treatment increases with improvements in
      antiviral therapy so the threshold for treatment falls. Trials reporting good
      responses to treatment in patients with mild disease support the case for
      widening access to treatment. Increasing recognition that chronic hepatitis C
      infection can lead to impairment of quality of life that is independent of liver
      histology is likely to result in more patients with mild hepatitis seeking
      treatment, more clinical trials that include patients with milder stages of liver
      disease, and greater enthusiasm for their inclusion in treatment guidelines.

PMID- 12072593
TI  - Screening for osteoporosis in patients with inflammatory bowel disease by using
      urinary N-telopeptides.
AB  - BACKGROUND: Patients with inflammatory bowel disease are at increased risk of
      osteoporosis. DESIGN AND METHODS: We carried out a prospective study of bone
      mineral density and biochemical markers of bone metabolism like osteocalcin and
      urinary N-telopeptides in 72 patients with inflammatory bowel disease and
      evaluated if one of these markers detects osteoporosis. In addition, bone mineral
      density and N-telopeptides were analysed retrospectively in a second series of 93
      patients with inflammatory bowel disease in order to assess predictive values
      found in the first patient group in an independent sample. RESULTS: Multiple
      linear regression showed that N-telopeptides (P < 0.0001) and total white blood
      cell count (P = 0.006) correlated negatively with the bone mineral density of the
      lumbar spine and only N-telopeptides (P = 0.005) correlated negatively with the
      bone mineral density of the femoral neck. Using receiver operator characteristic
      curves N-telopeptide concentrations of > 40 (30) nmol N-telopeptides/mmol
      creatinine were chosen as best cut-off values to exclude osteoporosis at the
      lumbar spine (femoral neck). Using these cut-off values a negative predictive
      value of 100% (100%) and a positive predictive value of 37.5% (27.9%) were found
      in the first group, and a negative predictive value of 95.2% (96%) and a positive
      predictive value of 15.6% (23.3%) in the second, independent group of patients.
      CONCLUSION: Our data suggest that N-telopeptide levels could be used as a tool
      for the screening of osteoporosis and for selecting those inflammatory bowel
      disease patients where bone mineral density measurement is indicated.

PMID- 12072594
TI  - Chronic nicotine administration differentially alters jejunal and colonic
      inflammation in interleukin-10 deficient mice.
AB  - BACKGROUND: Cigarette smoking alters the course of inflammatory bowel disease, is
      associated with protection against ulcerative colitis, but aggravates or has no
      effect on Crohn's disease. While the aetiology of this discrepancy remains
      unclear, differences between location of involvement in ulcerative colitis and
      Crohn's disease have not been examined in these studies. AIM: To examine the
      effects of nicotine administration on the course of jejunitis and colitis in
      interleukin-10 deficient mice. METHODS: Male C57/BL10 IL-10 -/- and wild type
      mice were given nicotine (12.5 microg/ml) in their drinking water at age 12-14
      weeks when they had developed clinical signs of inflammatory bowel disease.
      Gender and age matched control mice received tap water alone. All mice were
      killed after 2 weeks of treatment. Whole tissue sections of jejunum, proximal and
      distal colon were separated and examined by macroscopic and histological score.
      Northern blots were examined for somatostatin, intestinal trefoil factor and
      mucin-2. RESULTS: At 14-16 weeks, when the mice were killed, IL-10 -/- untreated
      control mice developed jejunitis (macroscopic score 1.4 +/- 0.5, microscopic
      score 2.0 +/- 0.2) and colitis (2.0 +/- 0.2 and 5.9 +/- 0.9, respectively). IL-10
      -/- mice treated for 2 weeks with nicotine had significantly reduced colonic
      scores (1.4 +/- 0.6 and 2.2 +/- 0.15, respectively). In contrast, the jejunum was
      more severely damaged (2.6 +/- 0.4 and 4.0 +/- 0.3; P = 0.01, respectively).
      Nicotine significantly increased both somatostatin and intestinal trefoil factor
      mRNA expression in the colon but not in the jejunum; no effect was noted on mucin
      2 or beta-actin mRNA expression. CONCLUSIONS: (1) Two weeks of nicotine
      administration leads to contrasting effects on jejunal and colonic inflammation
      in IL-10 -/- mice. (2) Nicotine ameliorated inflammation in the colon, which was
      associated with enhanced expression of two protective peptides.

PMID- 12072595
TI  - Impact of transjugular intrahepatic portosystemic stent-shunt for secondary
      prophylaxis of oesophageal variceal haemorrhage: a single-centre study over an 11
      year period.
AB  - AIMS: The role of various treatments for variceal haemorrhage is currently being
      evaluated. The purpose of this study was to analyse the impact of the use of
      endoscopic variceal sclerotherapy (EVS), variceal band ligation (VBL) and
      transjugular intrahepatic portosystemic stent-shunt (TIPSS) for secondary
      prophylaxis on the outcome of cirrhotic patients with the first episode of
      variceal haemorrhage presenting to a single centre. METHODS: Between 1986 and
      1996, data from 225 consecutive patients with the first episode of variceal
      haemorrhage were analysed. The modality of treatment for secondary prophylaxis
      between 1986 and 1991 was EVS (group I: n = 83; Child class C, 29%; mean follow
      up 36 +/- 3 months), between 1991 and 1993 VBL (group II: n = 56; Child class C,
      38%; mean follow-up 24 +/- 3 months), and between 1995 and 1996 TIPSS (group III:
      n = 86; Child class C, 60%; mean follow-up 17 +/- 1 months). Half of the patients
      between 1993 and 1995 underwent VBL and the other half had TIPSS. Data regarding
      rebleeding, mortality and encephalopathy were analysed using the Kaplan-Meier
      method. Cox's proportional hazard regression was used to test the significance of
      prognostic factors. RESULTS: Seventy-five per cent of patients re-bled in group
      I, 40% in group II, and 16% in group III (P < 0.0001). Mortality was
      significantly lower in the patients with Child class C disease in group III
      patients compared with those in groups I and II (P < 0.02). TIPSS was associated
      independently with reduced early mortality and re-bleeding. CONCLUSION: The
      results of this study suggest that TIPSS improves survival in patients with
      advanced liver disease and variceal haemorrhage, and should be considered for
      secondary prophylaxis in high-risk patients.

PMID- 12072596
TI  - High sustained response rate in patients with histologically mild (low grade and
      stage) chronic hepatitis C infection. A randomized, double blind, placebo
      controlled trial of interferon alpha-2b with and without ribavirin.
AB  - OBJECTIVE: To evaluate the efficacy and safety of therapy for patients with
      histologically mild hepatitis C virus (HCV) liver disease. DESIGN: A randomized,
      double blind, placebo controlled trial of interferon alpha-2b with or without
      ribavirin. SETTING: Regional and university hospitals. PARTICIPANTS: One hundred
      and sixteen treatment naive patients with mild chronic HCV infection. Mild HCV
      infection was defined according to Knodell as a grade score of > or = 1 and < or
      = 6 and a stage score of < or = 1. INTERVENTIONS: Interferon alpha-2b (3 MU three
      times weekly) for 52 weeks in combination with either ribavirin or a matched
      placebo. MAIN OUTCOME MEASURES: The study endpoint was the absence of HCV RNA in
      plasma and liver tissue 26 weeks post-treatment. In addition, liver histology was
      compared pre- and post-treatment. RESULTS: Combination therapy was superior to
      interferon monotherapy, with a virological sustained response rate of 54% (31/57)
      and 20% (12/59), respectively, in both serum and liver tissue (P = 0.001). The
      sustained response rate was higher with combination therapy than monotherapy both
      in genotype non-1 (81% vs 36%) and in genotype 1 (28% vs 4%). There was a
      significant improvement in mean grade score in all sustained responders,
      irrespective of treatment arm. CONCLUSION: Combination therapy with interferon
      and ribavirin was safe and as effective in patients with histologically mild HCV
      infection as previously reported for more advanced disease.

PMID- 12072597
TI  - What is an appropriate indication for endoscopic papillary balloon dilation?
AB  - OBJECTIVE: There are a number of views on the indication for endoscopic papillary
      balloon dilation (EPBD) in the management of bile duct stones. In this study, we
      have evaluated the efficacy and safety of EPBD compared with endoscopic
      sphincterotomy (EST). DESIGN: Prospective randomized trial. SETTING: One
      university hospital and one general hospital. PARTICIPANTS AND MAIN OUTCOME
      MEASURES: One hundred and forty patients were randomly allocated to EPBD or EST.
      Outcomes and complications were observed for a median period of 30 months.
      RESULTS: Both treatment approaches finally achieved similar success rates and
      needed similar numbers of treatment sessions for patients with stones less than
      10 mm in diameter. However, for patients with stones of 10 mm or more, EPBD
      required a significantly greater mean number of treatment sessions than EST (2.4
      vs 1.6, P < 0.01). Early complications occurred in seven EPBD (four pancreatitis,
      two cholangitis and one basket impaction) and eight EST (three pancreatitis, two
      bleeding and three cholangitis) patients. Late complications occurred in four
      EPBD (three recurrent bile duct stones and one cholecystitis) and six EST (three
      recurrent stones and three cholecystitis) patients. CONCLUSIONS: EPBD has little
      risk of bleeding. The technique removed small bile duct stones just as easily as
      did EST. These two procedures had approximately the same risk of pancreatitis and
      incidence of recurrent bile duct stones. Therefore, both procedures appear to be
      appropriate treatments for small bile duct stones. Whether or not EPBD becomes an
      established treatment will depend on further long-term studies.

PMID- 12072598
TI  - A survey of infectious agents as risk factors for primary sclerosing cholangitis:
      are Chlamydia species involved?
AB  - OBJECTIVES: The aetiology of primary sclerosing cholangitis (PSC) is unknown, and
      the role of micro-organisms has been studied only to a limited extent. We tested
      the hypothesis that past or persisting infection with common viruses or atypical
      bacteria might play a role in genetically susceptible hosts. DESIGN: Case-control
      study. METHODS: Serological screening for antibodies against 22 viruses as well
      as Chlamydia spp. and Mycoplasma pneumoniae was carried out in 41 well
      established PSC patients. All 5110 sera tested in 1997 for these micro-organisms
      at our laboratory served as a background reference group. Subsequently, Chlamydia
      anti-lipopolysaccharide (LPS) antibodies were determined by enzyme-linked
      immunosorbent assay (ELISA) in the PSC group and in three race-matched control
      groups (inflammatory bowel disease (IBD) group, n = 35; non-IBD patients group, n
      = 39; healthy blood donor group, n = 40). Subtyping in Chlamydia trachomatis and
      C. pneumoniae serotypes by specific anti-major outer membrane protein (MOMP)
      assays was carried out in the four groups. Immunohistochemical staining using
      specific markers for chlamydiae was carried out on liver biopsies of 14 PSC
      patients. RESULTS: There was a markedly elevated seroprevalence of Chlamydia-LPS
      antibodies compared with the 1997 reference group. The odds ratios (ORs) for the
      presence of immunoglobulin G, immunoglobulin M and immunoglobulin A antibodies
      for the PSC patients versus the control group were 2.4 (95% confidence interval
      (CI) 1.1 to 5.4), 1.9 (95% CI 0.9 to 4.0) and 6.7 (95% CI 3.0 to 17.0),
      respectively. All other micro-organisms tested showed normal antibody profiles
      that did not differ from the 1997 reference group. The seroprevalence of
      Chlamydia-anti-LPS antibodies was elevated markedly in the PSC patients compared
      with the IBD, non-IBD and blood donor groups. The outcomes in the C. trachomatis
      and C. pneumoniae anti-MOMP assays did not correlate with the anti-LPS-positive
      PSC sera. The actual presence of Chlamydia bodies in liver tissue could not be
      demonstrated. CONCLUSION: Our findings suggest an association between PSC and
      (previous) infection with Chlamydia.

PMID- 12072599
TI  - A double-blind, randomized comparison of omeprazole Multiple Unit Pellet System
      (MUPS) 20 mg, lansoprazole 30 mg and pantoprazole 40 mg in symptomatic reflux
      oesophagitis followed by 3 months of omeprazole MUPS maintenance treatment: a
      Dutch multicentre trial.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) have proved to be effective in treating
      reflux oesophagitis. Until now, no study had compared the PPIs omeprazole
      Multiple Unit Pellet System (MUPS), lansoprazole and pantoprazole in patients
      with reflux oesophagitis. AIM: To compare omeprazole MUPS 20 mg, lansoprazole 30
      mg and pantoprazole 40 mg for treatment effect in symptomatic reflux
      oesophagitis. METHOD: Patients with grade I-IV symptomatic reflux oesophagitis
      were randomized to double-blind omeprazole 20 mg once morning, lansoprazole 30 mg
      o.m. or pantoprazole 40 mg o.m. Patient satisfaction and symptoms were evaluated
      after 4 and 8 weeks. Patients not satisfied after 8 weeks were treated for
      another 4 weeks with omeprazole 40 mg MUPS (open). Successful treatment was
      followed by 3 months' maintenance treatment with omeprazole MUPS 20 mg (patients
      satisfied after 4 or 8 weeks) or omeprazole MUPS 40 mg (patients satisfied after
      12 weeks). RESULTS: On intention-to-treat (ITT) analysis (n = 461) at 4 and 8
      weeks, respectively, 84% and 87% (omeprazole MUPS), 78% and 81% (lansoprazole),
      and 84% and 89% (pantoprazole) were free of heartburn. Equivalence was found
      between omeprazole MUPS and pantoprazole (heartburn relief), but not with
      lansoprazole. Patient satisfaction after 4 and 8 weeks, respectively, was 79% and
      89% (omeprazole MUPS), 76% and 86% (lansoprazole), and 79% and 91%
      (pantoprazole). Patient satisfaction was similar in all treatment groups. During
      maintenance, 87% in the omeprazole MUPS 20 mg group and 81% in the omeprazole
      MUPS 40 mg group were satisfied after 3 months. CONCLUSIONS: Omeprazole MUPS 20
      mg and pantoprazole 40 mg have equivalent efficacy in the treatment of reflux
      oesophagitis. Based on patient satisfaction, omeprazole MUPS 20 mg, lansoprazole
      30 mg and pantoprazole 40 mg are equally effective.

PMID- 12072600
TI  - Photodynamic therapy of human Barrett's cancer using 5-aminolaevulinic acid
      induced protoporphyrin IX: an in-vivo dosimetry study in athymic nude mice.
AB  - OBJECTIVE: There has been a dramatic increase in recent years in the incidence of
      Barrett's oesophagus and the oesophageal adenocarcinoma associated with it.
      Alongside surgical treatment for early Barrett's carcinomas, endoscopic treatment
      procedures such as photodynamic therapy (PDT), which have much lower complication
      and mortality rates, will play an increasing role in the future. In this study,
      the effects of light energy dose, light fractionation and oxygenation on the
      efficacy of PDT were investigated for the first time in an in-vivo nude mice
      tumour model bearing a human Barrett's carcinoma. DESIGN: A total of 387 NMRI
      strain (nu/nu) nude mice with thymic aplasia (total 53 controls) were
      transplanted with human Barrett's carcinoma and treated with laser light at 635
      nm (light dose 0-200 J/cm2, fluence rate 400 mW/cm2). 5-Aminolaevulinic acid
      induced protoporphyrin IX (5-ALA-PpIX) (100 mg 5-ALA/kg body weight administered
      orally) was used as the photosensitizer. METHODS: Fractionation studies were
      performed at 0, 50, 100 and 150 J/cm2. The light dose was administered in four
      equal fractions divided by three irradiation-free intervals of 120 s. Oxygenation
      studies were carried out at 150 J/cm2 with simultaneous oxygen supply of 2, 6 and
      8 l oxygen/min. RESULTS: Dosimetry studies demonstrated a positive correlation
      between increase in light dose and tumour destruction up to 150 J/cm2 when using
      either continuous or fractionated light delivery. The optimal light energy dose
      was 150 J/cm2. Neither fractionation of light nor simultaneous oxygenation
      enhanced the efficacy of the PDT. CONCLUSION: This is the first study in the
      literature that proves the efficiency of PDT with 5-ALA-PpIX in human Barrett's
      adenocarcinoma and that demonstrates an exact dosimetry of the optimal light
      energy dose (150 J/cm2). No general recommendation can be made for the use of
      fractionation or oxygenation in clinical PDT.

PMID- 12072602
TI  - The influence of chronic pancreatitis on carcinogenesis: an experimental study in
      rats.
AB  - BACKGROUND: The literature contains many controversial or unclearly defined
      opinions about the risk of development of carcinoma of the exocrine part of the
      pancreas in patients with chronic pancreatitis. This and our own clinical
      observations based on analysis of patients with chronic pancreatitis treated
      surgically (anastomotic and resectional procedures) formed the background to an
      experimental study to define the risk of carcinogenesis in the course of chronic
      pancreatitis in rats. EXPERIMENTAL FINDINGS: In Wistar rats with chronic
      pancreatitis induced by etionine and then exposed to carcinogenic action of
      azaserine, proliferation, adenomas and acinic cell carcinomas of the exocrine
      part of the pancreas were diagnosed; the carcinomas were transplantable. In rats
      treated with azaserine only, benign proliferative lesions and adenomas were
      found. The presence of the p53 mutation protein was observed in carcinomatous
      pancreatic cells in malignant lesions of the pancreas in primary and
      transplantable cancers, but was not detected in benign proliferative lesions and
      adenomas. Chronic pancreatitis in Wistar rats predisposes the exocrine part of
      pancreas to malignant transformation. Growth of cancers of the exocrine part of
      the pancreas in male rats, but not in female rats, suggests hormonal
      determination of experimental pancreatic cancer. CONCLUSIONS: Results demonstrate
      that chronic pancreatitis in rats predisposes to malignant proliferative lesions,
      including acinic cell carcinoma. Expression of the protein product of p53 gene
      mutations correlated with neoplastic transformation of pancreas preceded by
      chronic pancreatitis, and was also detected in transplantable tumours.

PMID- 12072601
TI  - Helicobacter pylori infection and infertility.
AB  - OBJECTIVE: To determine (1) the prevalence of Helicobacter pylori infection in
      male and female patients with reproductive disorders and controls; (2) the
      presence of anti-H. pylori antibodies in samples of follicular fluid, vaginal
      secretions and sperm; and (3) the existence of a structural homology between a
      major spermatozoa protein, tubulin, and H. pylori proteins. PATIENTS AND METHODS:
      Serum samples from 167 patients with infertility and 837 age- and gender-matched
      controls (blood donors) were examined by enzyme-linked immunosorbent assay
      (ELISA) and Western blotting to determine the seropositivity for H. pylori
      infection. The presence of anti-H. pylori antibodies in samples of follicular
      fluid, vaginal secretions and sperm was determined using the same techniques. The
      possible cross-reactivity with spermatozoa of anti-H. pylori hyperimmune sera and
      human antibodies was studied by immunofluorescence. The N-acid homology of human
      tubulin with the principal H. pylori proteins was assayed by the WU-blastp
      program available on the Internet. RESULTS: The prevalence of infection was
      significantly higher in patients than controls (49.1% v. 33.5%, P < 0.001).
      Follicular fluids from infected patients contained specific antibodies in all
      cases, sperm samples in about 50% of cases, and vaginal secretions in a minority
      of cases. Sera to H. pylori whole antigens and VacA reacted with the tails and
      the pericentriolar area of human spermatozoa (which are rich in tubulin); sera to
      urease and heat-shock protein (Hsp) did not. Follicular fluids with anti-H.
      pylori antibodies immune reacted with spermatozoa. A linear homology was found
      between beta-tubulin and three H. pylori proteins, flagellin, VacA and CagA.
      CONCLUSIONS: H. pylori infection may increase the risk of developing reproductive
      disorders or worsen the clinical expression of this syndrome.

PMID- 12072603
TI  - Acute pancreatitis and the role of histamine-2 receptor antagonists: a meta
      analysis of randomized controlled trials of cimetidine.
AB  - OBJECTIVES: Acute pancreatitis is a common disorder. Histamine type-2 receptor
      antagonists (H2RAs) are frequently used in patients with acute pancreatitis to
      reduce pancreatic juice secretion. However, most of the studies on this topic
      have involved only a few patients, demonstrating no beneficial effect but without
      harm. To clarify this matter, a meta-analysis was conducted to assess the
      efficacy of H2RAs. METHODS: All randomized controlled trials written in English
      comparing the effects of H2RAs with those of placebo were retrieved. Clinical
      outcome data were extracted and the results pooled to yield odds ratios or
      weighted mean differences. Two investigators reviewed articles independently and
      reached a consensus. RESULTS: A total of 285 patients from five studies were
      included. Cimetidine was the only H2RA used to treat acute pancreatitis. The
      pooled odds ratio of complications for H2RAs versus placebo was 1.64 (95%
      confidence interval [CI] 0.92 to 2.92). A weighted mean difference of duration of
      pain was 6.96 h (95% CI -2.50 to 16.43 h) in favour of placebo. CONCLUSIONS:
      Cimetidine is not more effective than placebo in reducing acute pancreatitis
      related complications and the duration of pain; rather, the use of cimetidine for
      acute pancreatitis could be associated with higher rates of complications and
      pain. Until the results of a large randomized trial show otherwise, H2RAs should
      not be used in the absence of specific clinical indications.

PMID- 12072605
TI  - Acute hepatitis associated with herb (Teucrium capitatum L.) administration.
AB  - Drug-induced hepatotoxicity due to medicinal plant administration has been
      infrequently reported. This case describes a 62-year-old Caucasian man with
      hypercholesterolaemia and hyperglycaemia, who started daily consumption of a tea
      containing the medicinal plant Teucrium capitatum L. Four months after initiation
      of this therapy he developed an acute icteric hepatitis-like illness. Other
      causes of acute hepatocellular necrosis were excluded. Liver histology
      demonstrated changes consistent with acute hepatitis with bridging necrosis. The
      medicinal plant was withdrawn. The patient recovered clinically and serum
      bilirubin and aminotransferases returned to normal levels within a 9-week time
      period. To the best of our knowledge, this is the first description of acute
      hepatitis associated with T. capitatum administration. This case suggests that T.
      capitatum can induce acute icteric hepatocellular necrosis, which could be
      clinically confused with acute viral hepatitis, and that some medicinal plants
      are not as safe as they are widely considered.

PMID- 12072604
TI  - Alpha-fetoprotein- and des-gamma-carboxy prothrombin-producing advanced gastric
      cancer.
AB  - A case of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP)
      producing gastric cancer with multiple liver metastasis is reported. The
      simultaneous presence of Borrmann I gastric cancer and IIa aggregating type
      gastric cancer was noted. Borrmann I gastric cancer was a poorly differentiated
      adenocarcinoma, while IIa aggregating type gastric cancer was a moderately
      differentiated adenocarcinoma. Plasma levels of AFP and DCP were 247,000 ng/ml
      and 320,000 mAU/ml, respectively. Immunohistochemical staining confirmed the
      production of these two proteins in Borrmann I gastric cancer.

PMID- 12072606
TI  - Mesenteric vein thrombosis triggered by blunt abdominal trauma in a patient with
      the primary antiphospholipid syndrome.
AB  - The antiphospholipid syndrome is defined by the presence of autoimmune
      antiphospholipid antibodies in serum together with venous, arterial or small
      vessel thrombosis and/or morbidity with pregnancy. Superior mesenteric vein
      thrombosis represents a rare complication associated with this syndrome;
      triggering events such as surgical procedures, drug administration and
      anticoagulation withdrawal have been reported. We describe a case of superior
      mesenteric vein thrombosis triggered by blunt abdominal trauma in a 47-year-old
      man with the primary antiphospholipid syndrome. It confirms a previous report
      describing a patient suffering from the catastrophic antiphospholipid syndrome
      after a fall. This provides evidence, previously unreported, for the possible
      role of trauma as a precipitating factor leading to thrombosis, even in cases of
      'simple' antiphospholipid syndromes. Our patient required extensive small-bowel
      resection but could be discharged after complete recovery.

PMID- 12072607
TI  - A case of a lipoma in the colon complicated by intussusception.

PMID- 12072608
TI  - Views on esomeprazole-based triple therapy to treat duodenal ulcer disease and
      Helicobacter pylori infection.

PMID- 12072610
TI  - Results from a European clinical investigation of the Nucleus multichannel
      auditory brainstem implant.
AB  - OBJECTIVE: This study was designed to investigate the perceptual benefits and
      potential risks of implanting the Nucleus(R) multichannel auditory brainstem
      implant. DESIGN: Between September 1992 and October 1997 a total of 27 subjects
      received a Nucleus 20- or 21-channel Auditory Brainstem Implant (ABI). All
      subjects involved in the trial had bilateral acoustic tumour as a result of
      neurofibromatosis type 2 (NF2) resulting in complete dysfunction of the VIIIth
      nerve. The study used each subject as their own control without a preoperative
      baseline because residual hearing, if existing, was destroyed at surgery by
      tumour removal. A battery of speech tests was conducted to evaluate each
      patient's performance and communication abilities. Tests were conducted, where
      possible, in the auditory-only, visual-only, and auditory-visual conditions at 3
      days postoperatively (baseline), at 3-mo intervals for the first year and every
      12 mo thereafter. A subjective performance questionnaire was administered
      together with an extensive neurological examination at each test interval.
      RESULTS: 27 subjects involved in this trial were successfully implanted with a
      Nucleus ABI. One subject died 2 days postoperatively due to a lung embolism
      unrelated to the device. Twenty-six subjects underwent device activation and all
      but one patient received auditory sensation at initial stimulation (96.2%). On
      average 8.6 (+/-4.2) of the available 21 electrodes were used in the patients'
      MAPs. Performance evaluation measures showed that the majority of users had
      access to auditory information such as environmental sound awareness together
      with stress and rhythm cues in speech that assist with lipreading. Although most
      subjects did not achieve any functional auditory-alone, open-set speech
      understanding, two subjects from this series (7.4%) did receive sufficient
      benefit to be able to use the ABI in conversation without lipreading.
      CONCLUSIONS: Although the medical risks and surgical complexity associated with
      ABI device implantation are far greater than those for a cochlear implant, the
      clinical results from this trial show that the Nucleus multichannel ABI is
      capable of providing a significant patient benefit over risk ratio for subjects
      suffering loss of hearing due to bilateral retrocochlear lesions.

PMID- 12072611
TI  - Initial evaluation of the Clarion CII cochlear implant: speech perception and
      neural response imaging.
AB  - OBJECTIVE: To evaluate the new Clarion CII cochlear implant with the perimodiolar
      HiFocus electrode array, including both speech perception outcomes and the
      device's capabilities of measuring the electrically evoked compound action
      potential (eCAP) of the auditory nerve (Neural Response Imaging, NRI). DESIGN:
      The speech perception scores on CVC words without lip reading were monitored
      prospectively for the 10 postlingually deaf patients implanted with the Clarion
      CII device in the period July 2000 until May 2001 in the Leiden University
      Medical Center. Preoperative and postoperative NRI recordings were made, applying
      various combinations of monopolar stimulating and recording electrodes with the
      alternating polarity paradigm available in the test bench software. RESULTS: Nine
      patients preferred the CIS, one the PPS strategy, none the SAS strategy. With
      their favorite strategy they acquired significant open set speech understanding
      within a few weeks, resulting in an average CVC phoneme score of 84% (word score
      66%) at the end of the study (follow-up 3 to 11 mo). In speech-shaped noise, the
      average phoneme recognition threshold (PRT) was reached at a signal to noise
      ratio just below 0 dB. The NRI recordings had clear N1 and P1 peaks if there was
      at least one contact between the stimulating and recording electrodes,
      necessitating just 15 sweeps for a reliable recording. We observed considerable
      inter-patient and inter-electrode variability, but for a given situation NRI
      input/output curves were stable over time. More apical contacts generally
      elicited larger eCAPs. Response amplitudes tended to peak at recording sites
      around apical and basal stimulating electrodes, suggesting a limited spread of
      excitation. Preliminary recordings with the forward masking paradigm were
      consistent with the ones with the alternating polarity scheme. CONCLUSIONS: The
      Clarion CII is a promising cochlear implant with which our first 10 patients have
      obtained excellent speech perception results. The NRI system yields high quality
      signals with a limited number of sweeps at a high sampling rate.

PMID- 12072612
TI  - Speech understanding in quiet and noise in bilateral users of the MED-EL COMBI
      40/40+ cochlear implant system.
AB  - OBJECTIVE: The purpose of the study was to investigate speech understanding in
      quiet and noise in subjects bilaterally implanted with multi-channel cochlear
      implants. DESIGN: Nine adults bilaterally implanted with MED-EL implants were
      included in the study. The subjects were tested in three conditions: with both
      implants, with the right implant only, and with the left implant only. Speech
      tests included monosyllables in quiet and sentences in noise (10 dB signal to
      noise ratio). Speech was presented from the front, and noise was presented from
      either 90 degrees or 270 degrees azimuth. RESULTS: All subjects reported benefit
      from bilateral stimulation. Speech scores for all subjects were higher with
      bilateral than with unilateral stimulation. The average score across subjects for
      sentence understanding was 31.1 percentage points higher with both cochlear
      implants compared with the cochlear implant ipsilateral to the noise, and 10.7
      percentage points higher with both cochlear implants compared with the cochlear
      implant contralateral to the noise. The average score for recognition of
      monosyllabic words was 18.7 percentage points higher with both cochlear implants
      than with one cochlear implant. All of these differences in average scores were
      significant at the 5% level. CONCLUSIONS: Bilateral cochlear implantation
      provides a significant benefit in speech understanding in both quiet and noise.

PMID- 12072613
TI  - Speech recognition with the nucleus 24 SPEAK, ACE, and CIS speech coding
      strategies in newly implanted adults.
AB  - OBJECTIVE: The objective of this study was to determine whether 1) the SPEAK, ACE
      or CIS speech coding strategy was associated with significantly better speech
      recognition for individual subjects implanted with the Nucleus CI24M internal
      device who used the SPrint speech processor, and 2) whether a subject's preferred
      strategy for use in everyday life provided the best speech recognition. DESIGN:
      Twelve postlinguistically deaf, newly implanted adults participated. Initial
      preference for the three strategies was obtained with paired-comparison testing
      on the first day of implant stimulation with seven of eight U.S. subjects. During
      the first 12 wk, all subjects used each strategy alone for 4 wk to give them
      experience with the strategy and to identify preferred speech processor program
      parameters and settings that would be used in subsequent testing. For the next 6
      wk, subjects used one strategy at a time for 2-wk intervals in the same order
      they had for the first 12 wk. At the end of each 2-wk interval, speech
      recognition testing was conducted with all three strategies. At the end of the 6
      wk, all three strategies were placed on each subject's processor, and subjects
      were asked to compare listening with these three programs in as many situations
      as possible for the next 2 wk. When they returned, subjects responded to a
      questionnaire asking about their preferred strategy and responded to two lists of
      medial consonants using each of the three strategies. The U.S. subjects also
      responded to two lists of medial vowels with the three strategies. RESULTS: Six
      of the 12 subjects in the present study had significantly higher CUNY sentence
      scores with the ACE strategy than with one or both of the other strategies; one
      of the 12 subjects had a significantly higher score with SPEAK than with ACE. In
      contrast, only two subjects had significantly higher CNC word and phoneme scores
      with one or two strategies than with the third strategy. One subject had a
      significantly higher vowel score with the SPEAK strategy than with the CIS
      strategy; and no subjects had significantly higher consonant scores with any
      strategy. Seven of 12 subjects preferred the ACE strategy, three preferred the
      SPEAK strategy, and two preferred the CIS strategy. Subjects' responses on a
      questionnaire agreed closely with strategy preference from comparisons made in
      everyday life. There was a strong relation between the preferred strategy and
      scores on CUNY sentences but not for the other speech tests. For all subjects,
      except one, the preferred strategy was the one with the highest CUNY sentence
      score or was a strategy with a CUNY score not significantly lower than the
      highest score. CONCLUSIONS: Despite differences in research design, there was
      remarkably close agreement in the pattern of group mean scores for the three
      strategies for CNC words and CUNY sentences in noise between the present study
      and the Conversion study (Arndt, Staller, Arcaroli, Hines, & Ebinger, Reference
      Note 1). In addition, essentially the same percentage of subjects preferred each
      strategy. For both studies, the strategy with which subjects had the highest
      score on the CUNY sentences in noise evaluation was strongly related to the
      preferred strategy; this relation was not strong for CNC words, CNC phonemes,
      vowels or consonants (Skinner, Arndt, & Staller, 2002). These results must be
      considered within the following context. For each strategy, programming
      parameters preferred for use in everyday life were determined before speech
      recognition was evaluated. In addition, implant recipients had experience
      listening with all three strategies in many situations in everyday life before
      choosing a preferred strategy. Finally, 11 of the 12 subjects strongly preferred
      one of the three strategies. Given the results and research design, it is
      recommended that clinicians fit each strategy sequentially starting with the ACE
      strategy so that the preferred programming parameters are determined for each
      strategy before recipients compare pairs of strategies. The goal is to provide
      the best opportunity for individuals to hear in everyday life within a clinically
      acceptable time period (e.g., 6 wk).

PMID- 12072614
TI  - The effect of midline petrous apex lesions on tests of afferent and efferent
      auditory function.
AB  - OBJECTIVES: Historically, audiological procedures have focused on the assessment
      of the afferent (ascending) cochlear-VIIIth nerve system and have, for the most
      part, ignored the efferent (descending) auditory system. We report afferent and
      efferent auditory test results for two cases with a cholesterol cyst of the right
      petrous apex; one lesion involves the afferent segment of the auditory system,
      and the second lesion involves both the afferent and efferent segments of the
      auditory system. These "natural experiments" provide a unique opportunity to
      study the effect of a space-occupying lesion of the petrous apex on afferent and
      efferent function of the auditory system. DESIGN: Transient evoked otoacoustic
      emission (TEOAE) suppression studies were performed to assess the effect of the
      cholesterol cyst on the efferent system of the two cases. In addition, three
      complementary afferent tests of brain stem auditory function were administered:
      1) acoustic reflex thresholds (ARTs); 2) masking level difference (MLD); and 3)
      auditory brain stem response (ABR). These tests are complementary because the
      superior olivary complex (SOC) is involved not only in the mediation of the sound
      evoked efferent reflex assessed in TEOAE suppression, but in the mediation of the
      ARTs, the MLD, and the ABR. RESULTS: The two cases with midline petrous apex
      lesions, one not involving the VIII-cochlear efferent auditory system, differed
      from each other with regards to TEOAEs suppression, and ARTs. Specifically, the
      case with only afferent involvement produced normal TEOAE suppression, a normal
      MLD, normal ARTs, and abnormal waves III and V of the ABR, whereas the case with
      both afferent and efferent involvement produced abnormal TEOAE suppression, a
      normal MLD, abnormal ARTs, and abnormal waves III and V of the ABR. CONCLUSIONS:
      These cases illustrate that although several auditory tests can be mediated
      within the same or adjacent anatomical structures, i.e., the SOC, they may not be
      equally affected by the same lesion due to different physiology. Further, the
      TEOAE suppression paradigm is a clinically relevant test to assay the sound
      evoked efferent reflex that is mediated by the medial olivocochlear system of the
      SOC.

PMID- 12072615
TI  - Vestibular evoked myogenic potentials are intact after sudden deafness.
AB  - OBJECTIVE: To evaluate vestibular evoked myogenic potentials (VEMPs) in cases of
      sudden deafness, and to confirm the noncochlear origin of the VEMPs. STUDY
      DESIGN: Prospective study. VEMPs, which were evoked by short tone burst (95 dB
      nHL) stimulation, were recorded in 20 patients with unilateral, idiopathic sudden
      deafness. The results of the deaf ears were compared with those of the
      contralateral healthy ears and the normal control ears. The relations between
      VEMPs and the hearing level or caloric response were then investigated. RESULTS:
      All 20 of the deaf ears displayed normal biphasic VEMPs. The mean latencies of
      p13 and n23, as well as mean amplitude p13-n23, were 15.1 +/- 2.8 msec, 20.7 +/-
      3.3 msec and 25.2 +/- 12.6 microV, respectively, not significantly different to
      either the contralateral healthy ears (p > 0.05) or the normal control ears (p >
      0.05). Five deaf ears displayed canal paresis or absent caloric response, whereas
      the remaining 15 ears revealed normal caloric response. CONCLUSION: All the
      lesioned ears of patients with idiopathic sudden deafness exhibit normal biphasic
      VEMPs. Neither the hearing level nor the caloric response correlated to the
      VEMPs.

PMID- 12072617
TI  - Auditory cortical response patterns to multiple rhythms of AM sound.
AB  - OBJECTIVE: Multiple amplitude modulation (AM) of a tone results in a time series
      with a complex structure of envelope fluctuations. In this study the cortical
      responses elicited by such an auditory stimulus were investigated. It was
      hypothesized that the auditory cortex responds simultaneously with different
      patterns of activity corresponding to the different rhythm of periodical stimulus
      fluctuations. The relations of these response patterns to either steady-state
      responses (SSR) in the 40 Hz range or the transient slow auditory evoked
      responses were investigated. DESIGN: Auditory evoked magnetic fields were
      recorded from the left temporal cortex of nine healthy humans in response to 250
      Hz tones that were amplitude modulated with the sum of two sinusoids of 38 and 40
      Hz. The stimulus was presented continuously to the subject's right ear at the
      intensity of 70 dB sensation level. In addition, the responses to 250 Hz tone
      burst stimuli with duration of 20, 50, 100, and 200 msec, respectively, were
      recorded. The tone-bursts were presented at an inter-stimulus interval (ISI) of
      0.5 sec, which was equivalent to the slowest rhythm of the multiple-AM stimulus.
      Magnetic source analysis was applied to all elicited waveforms. RESULTS: From all
      subjects SSR at 38 and 40 Hz were clearly recognizable and were superimposed by a
      periodical response pattern corresponding to 2 Hz stimulus envelope fluctuations.
      A positive peak with latency of 70 msec was the mostly pronounced response to
      tone-burst stimulation at the ISI of 0.5 sec and resembles the low-frequency
      response pattern to the AM stimulus. The N1-P2 complex showed an almost complete
      suppression at 0.5 sec ISI. In contrast, it was the most prominent evoked
      response activity when using a longer ISI of 3 sec. Source locations in
      overlapping areas were estimated for the SSR in the 40 Hz range, the prominent
      peak of low-frequency response to the AM stimulus, and the P1 peak at tone-burst
      stimulation, respectively. These were separated from the N1 source location by
      about 0.5 cm in anterior and 0.5 cm in medial direction. CONCLUSION: As a result
      of multiple AM the stimulus signal envelope fluctuates with frequencies of 2 Hz
      and around 40 Hz. The auditory cortex responds to this stimulus with different
      response patterns. Both modulation signals at 38 and 40 Hz were almost linearly
      represented as steady-state responses. The evoked response patterns to stimulus
      fluctuations at low-frequency rhythm resemble the slow cortical auditory evoked
      responses. The 2 Hz stimulus rhythm is perceived as loudness fluctuation, and 40
      Hz modulation is perceived as a rough sound. It is assumed that the different
      cortical representations correspond to both types of perception of the complex AM
      sound.

PMID- 12072616
TI  - Speech perception and cortical event related potentials in children with auditory
      neuropathy.
AB  - OBJECTIVES: 1) To investigate the unaided and aided speech perception abilities
      of children with auditory neuropathy (AN) and to compare their performance to
      children with sensorineural hearing loss. 2) To establish whether cortical event
      related potentials (ERPs) could be recorded in children with AN, and to determine
      the relationship between the presence of these responses and speech perception.
      DESIGN: Unaided and aided speech perception assessments (PBK words), and cortical
      ERP testing was carried out in a group of 18 children with AN. Data also were
      obtained from a cohort of age and hearing level matched children with
      sensorineural hearing loss. RESULTS: The speech perception performance of the 15
      children with AN able to complete a PBK-word assessment, fell into two distinct
      categories. The children either showed no open-set speech perception ability
      (7/15 cases), or performance levels similar to their sensorineural counterparts
      (8/15 cases). Approximately 50% of children with AN showed ERPs of normal
      latency, amplitude and morphology. In all cases, response presence (at normal
      latencies) was consistent with reasonable speech perception ability, and response
      absence was consistent with negligible speech perception. CONCLUSIONS: In
      approximately 50% of children with auditory neuropathy, the provision of
      amplification results in significant open-set speech perception improvements. The
      results confirm the previously published reports that speech perception ability
      cannot be reliably estimated from the behavioral audiogram in children with AN.
      Obligatory ERP test results may offer a means of predicting perceptual skills in
      newly diagnosed youngsters as the presence of ERPs (with age-appropriate latency
      and morphology) was correlated with significant open set speech perception
      abilities and amplification benefit. The absence of the ERP in contrast,
      indicated profound hearing disability evidenced by profound hearing loss and/or
      extremely poor speech perception.

PMID- 12072620
TI  - Scientific data from clinical trials: investigators' responsibilities and rights.

PMID- 12072621
TI  - Randomized, double-blind, placebo-controlled trial of sildenafil (Viagra) for
      erectile dysfunction after rectal excision for cancer and inflammatory bowel
      disease.
AB  - PURPOSE: Controlled trials have demonstrated the efficacy of sildenafil for
      "mixed etiology" erectile dysfunction, but this may not be the case if there is
      underlying pelvic parasympathetic nerve damage. We aimed to determine the
      efficacy of sildenafil after rectal excision for rectal cancer and inflammatory
      bowel disease. METHODS: Patients with erectile dysfunction after rectal excision
      were randomly assigned in a double-blind manner to sildenafil or placebo groups.
      After unblinding, placebo patients crossed over to open sildenafil. Primary end
      points were improvement in erectile function on a global efficacy question and
      erectile function questionnaire scores. Secondary end points were frequency and
      severity of side effects. RESULTS: Thirty-two patients were randomly assigned,
      and two dropped out before randomization. Fourteen received sildenafil, and 18
      received placebo. Eleven (79 percent) of 14 responded to sildenafil, on global
      efficacy assessment, compared with 3 (17 percent) of 18 taking placebo (mean
      difference, 61.9 percent; 95 percent confidence interval, 34.4 to 89.4 percent; P
      = 0.0009). Sildenafil improved both erectile function domain scores (mean
      difference, 13.3; 95 percent confidence interval, 7.9 to 18.7; P = 0.0001) and
      total International Index of Erectile Function scores (mean difference, 30.6; 95
      percent confidence interval, 18.7 to 42.6; P < 0.0001) from pretreatment baseline
      scores. Placebo did not produce improvement in either erectile function (mean
      difference, 1.7; 95 percent confidence interval, -0.8 to 4.2; P = 0.16) or total
      International Index of Erectile Function scores (mean difference, 5; 95 percent
      confidence interval, -1.1 to 11.1; P = 0.1). Ten (100 percent) of 10 crossover
      patients not responding to placebo did respond to sildenafil (difference, 100
      percent; P < 0.0001). Sildenafil improved both erectile function domain scores
      (mean difference, 16.8; 95 percent confidence interval, 9.7 to 24; P = 0.002) and
      total International Index of Erectile Function scores (mean difference, 29.5; 95
      percent confidence interval, 15.8 to 43.2; P = 0.003) from precrossover baseline
      scores. Seven (50 percent) of 14 patients on sildenafil compared with 4 (22
      percent) of 18 on placebo experienced side effects (difference, 28 percent; 95
      percent confidence interval, -4.4 to 60.4 percent; P = 0.14), 91 percent of which
      were mild and well tolerated. CONCLUSION: Sildenafil completely reverses or
      satisfactorily improves postproctectomy erectile dysfunction in 79 percent of
      patients. Side effects are usually mild and well tolerated. The damage incurred
      by the pelvic nerves after proctectomy, less profound than after prostatectomy,
      is likely to result in a partial parasympathetic nerve lesion.

PMID- 12072622
TI  - Mesorectal microfoci adversely affect the prognosis of patients with rectal
      cancer.
AB  - PURPOSE: Mesorectal involvement is a common feature in rectal tumors. Neoplastic
      foci can be identified at pathologic examination of the mesorectum, but their
      incidence and prognostic significance remain to be defined. METHODS: A series of
      77 patients with extraperitoneal rectal cancer, resected with total mesorectal
      excision, entered the study. After fixation, the excised specimens were submitted
      to serial transverse sections and staining. Direct tumor infiltration, lymph node
      involvement, and neoplastic microfoci in the mesorectum were investigated.
      Patients with mesorectal foci were compared with those without deposits with
      regard to clinical and pathologic parameters; different patterns of foci
      (endovasal, endolymphatic, perineural, isolated) were also considered. Univariate
      and multivariate analyses were used to evaluate the impact on survival rate.
      RESULTS: Neoplastic mesorectal involvement was found in 64 patients (83.1
      percent). Direct tumor infiltration was detected in 66.2 percent, node
      involvement in 28.6 percent, microscopic foci in 44.2 percent of cases (endovasal
      in 11.7 percent, endolymphatic in 15.7 percent, perineural in 26 percent,
      isolated in 14.3 percent). In 7 cases (10.9 percent) microfoci alone (without any
      kind of other mesorectal involvement) were detected. Deposits were found in 18.8
      percent of TNM Stage I tumors, in 46.9 percent of Stage II and in 59.3 percent of
      Stage III cancers. Similar incidence was found in patients treated with
      integrated therapies and surgery alone (43.3 vs. 44.7 percent, P = not
      significant). Poorer median (44.5 vs. 57 months, P = 0.04) five-year overall
      survival rate (43.4 vs. 63.3 percent, P = 0.016) and disease-free survival rate
      (43.3 vs. 57.7 percent, P = 0.048) were observed in patients with microscopic
      foci compared with those without deposits. Tumor configuration was found to be a
      independent prognostic factor for both overall and disease-free survival rates;
      furthermore, endolymphatic, perineural, and isolated foci significantly affected
      overall survival rate, while TNM staging affected disease-free survival rate.
      CONCLUSIONS: The incidence of neoplastic foci in the mesorectum is high, even in
      early staged tumors and despite aggressive preoperative treatment. They seem to
      affect prognosis. Such features should, therefore, be considered when local
      excision of the tumor is planned. Presence of mesorectal foci should modify
      conventional staging of the rectal tumor.

PMID- 12072624
TI  - Discontinuous rectal cancer spread in the mesorectum and the optimal distal
      clearance margin in situ.
AB  - PURPOSE: We examined the frequency, mode, and extent of discontinuous spread of
      rectal cancer in the mesorectum to determine the optimal distal clearance margin
      in situ. METHODS: Forty consecutive patients with rectal cancer undergoing
      locally curative resection were studied prospectively. Discontinuous cancer
      spread in the mesorectum and the extent of distal spread was examined
      microscopically. A tissue shrinkage ratio comparing the distal clearance margin
      measured before transection to that measured after fixation in each case, was
      used to convert microscopically measured extent of distal spread to extent in
      situ. RESULTS: Discontinuous cancer spread in the mesorectum was observed in 17
      cases (43 percent); lymph node metastasis in 15 cases (38 percent) and small
      deposits other than nodal metastases in 8 cases (20 percent). Distal cancer
      spread (either intramural or mesorectal) was observed in 6 cases (15 percent).
      The mean distal clearance margin before transection and after fixation was 3.2 cm
      and 2 cm, respectively. The mean tissue shrinkage ratio was 60 percent. The
      maximum extent of microscopic distal spread and adjusted distal spread in situ
      were 20 and 24 mm, respectively. CONCLUSIONS: Excising the mesorectum with fascia
      propria circumferentially intact is essential for rectal surgery. The optimal
      distal clearance margin for the rectal wall as well as the mesorectum in situ can
      be reduced to 3 cm with a right angle.

PMID- 12072625
TI  - Incidence and prognostic implications of isolated tumor cells in lymph nodes from
      patients with Dukes B colorectal carcinoma.
AB  - PURPOSE: Lymph node metastasis in colorectal carcinoma is an important prognostic
      factor, yet the prognostic relevance of occult tumor cells in lymph nodes has not
      elucidated. This study was performed to investigate the correlation between
      isolated tumor cells in lymph nodes and malignancy potential in patients with
      Dukes B colorectal carcinoma and, thus, to determine whether presence of isolated
      tumor cells in lymph nodes has a prognostic significance. METHODS: To evaluate
      the incidence of isolated tumor cells in lymph nodes in patients with Dukes B
      colorectal carcinoma, 1,808 lymph nodes taken from 93 patients (19.4 per case)
      were assessed by immunohistochemical technique using a monoclonal antihuman
      cytokeratin (MNF 116). Clinicopathologic parameters and prognosis were compared
      between patients with and without isolated tumor cells. RESULTS: Isolated tumor
      cells were identified in 54 lymph nodes from 29 patients (31.2 percent) by the
      immunostaining. No correlations were observed between the incidence of positive
      isolated tumor cells and various clinicopathologic parameters, including
      preoperative carcinoembryonic level, tumor site and size, histologic
      differentiation, pT stage, vascular invasion and lymphatic invasion, and
      perineural invasion. There was no difference in five-year survival estimated by
      Kaplan-Meier life-table method between positive and negative groups for isolated
      tumor cells (82.8 and 85.9 percent, respectively). Multivariate analyses showed
      that sex (P = 0.0236), serum carcinoembryonic level (>or= 5 ng/ml, P = 0.0002),
      and lymphatic vessel invasion (P = 0.0002) were significant factors in the
      survival time. CONCLUSION: Immunohistochemical staining with an anticytokeratin
      antibody is useful in identifying isolated tumor cells in lymph nodes missed in
      routine hematoxylin-eosin staining, but clinically it seems to be of little
      prognostic value in patients with Dukes B colorectal carcinoma. Thus, this
      immunostaining technique does not offer a significant benefit of different
      strategies for additional therapy or follow-up during conventional pathologic
      staging using hematoxylin-eosin staining.

PMID- 12072627
TI  - Extraction and analysis of carcinoembryonic antigen in lymph nodes: a new
      approach to the diagnosis of lymph node metastasis of colorectal cancer.
AB  - PURPOSE: To detect lymph node metastasis of colorectal cancer, we extracted
      protein from lymph nodes and determined the concentration of carcinoembryonic
      antigen. METHODS: In Experiment 1, a total of 237 lymph nodes from 23 colorectal
      cancer patients were examined histologically after immersion in 200 microl of
      saline for 2 hours. Concentrations of protein and carcinoembryonic antigen in
      each saline sample were determined by protein assay and immunoradiometric assay,
      respectively. Each value of carcinoembryonic antigen in the saline was divided by
      extracted protein, and the carcinoembryonic antigen levels in lymph nodes were
      represented as nanograms per milligram of protein. In Experiment 2, 63 lymph
      nodes from 8 colorectal cancer patients were cut into 2 pieces and immersed in 1
      ml of saline for 15 minutes, and they were subjected to reverse transcriptase
      polymerase chain reaction for carcinoembryonic antigen and histologic
      examination, respectively, after measurement of the carcinoembryonic antigen
      concentration in the extract. RESULTS: From 236 of 237 lymph nodes in Experiment
      1, an average of 3,249.4 microg/ml protein was successfully extracted. Histologic
      examination revealed that 33 of 236 lymph nodes had colorectal cancer metastases,
      with a significantly higher concentration of carcinoembryonic antigen on average
      (655.5 ng/mg protein) than in the 203 lymph nodes without metastasis (18.2 ng/mg
      protein; P < 0.0001). In Experiment 2, 19 of 63 lymph nodes examined were
      positive for metastasis in both reverse transcriptase-polymerase chain reaction
      and histology and showed a significantly higher carcinoembryonic antigen
      concentration on average (1,003.9 ng/mg protein) than the 42 lymph nodes that
      demonstrated no metastasis by either method (18.0 ng/mg protein; P < 0.0001). The
      remaining two lymph nodes, which were positive by reverse transcriptase
      polymerase chain reaction but negative by histology, showed high carcinoembryonic
      antigen concentrations of 514.7 and 61,970.5 ng/mg protein, respectively.
      CONCLUSION: This simple method of protein extraction and determination of
      carcinoembryonic antigen concentration in lymph nodes may provide an alternative
      tool for the diagnosis of colorectal cancer metastasis.

PMID- 12072628
TI  - Strictureplasty in diffuse Crohn's jejunoileitis: safe and durable.
AB  - PURPOSE: As an alternative to resection, strictureplasty may allow for
      preservation of intestinal length and avoidance of short-bowel syndrome in
      patients with diffuse Crohn's jejunoileitis. However, the long-term durability of
      the procedure and its safety have not been confirmed. The purpose of this study
      was to report our experience with strictureplasty for diffuse Crohn's
      jejunoileitis. METHODS: Between 1984 and 1999, 123 patients underwent a
      laparotomy that included an index strictureplasty for diffuse jejunoileitis.
      Patient history, operative details, and postoperative morbidities were obtained
      by chart review. Nineteen patients (15 percent) were receiving total parenteral
      nutrition for short-bowel syndrome, and 81 (66 percent) were taking chronic
      steroids. Total number of strictureplasties performed was 701 (median,
      5/patient). Seventy percent of patients underwent a synchronous bowel resection.
      Follow-up information was determined by personal or phone interviews. Recurrence
      was defined as the need for reoperation, and risk was calculated by the Kaplan
      Meier method. Patients with diffuse jejunoileitis were also compared with 219
      patients with limited small-bowel Crohn's disease undergoing strictureplasty.
      RESULTS: The overall morbidity rate was 20 percent, with septic complications
      occurring in 6 percent. The surgical recurrence rate was 29 percent with a median
      follow-up period of 6.7 (range, 1-16) years. The recurrence rate in diffuse
      jejunoileitis patients did not differ from that seen in patients with limited
      small-bowel Crohn's disease (P = 0.38). Short duration of disease and short
      interval since last surgery were significant predictors of accelerated recurrence
      (P = 0.008 and 0.04, respectively). CONCLUSIONS: Strictureplasty is a safe and
      durable alternative to resection in diffuse Crohn's jejunoileitis. Patients with
      a short duration of disease and short interval since last surgery are at higher
      risk for accelerated recurrence. Patients with diffuse jejunoileitis do not
      appear to be at higher risk for recurrence than patients with more limited
      Crohn's disease.

PMID- 12072629
TI  - Remicade does not abolish the need for surgery in fistulizing Crohn's disease.
AB  - PURPOSE: Tumor necrosis factor antagonist therapy in the form of infliximab has
      been shown to promote significant healing in fistulizing Crohn's disease and
      therefore is often considered as a possible alternative to surgery. Our aim was
      to evaluate the role of infliximab in supplanting surgery for fistulizing Crohn's
      disease. METHODS: We performed a retrospective chart review of all adult patients
      who received infliximab for fistulizing Crohn's disease at one institution
      between September 1998 and October 2000. RESULTS: Twenty-six patients (14 male;
      mean age, 38 years; range, 19-80 years) received a mean of three (range, one to
      six) doses of infliximab (5 mg/kg) with the intent to cure fistulizing Crohn's
      disease. Nine patients (35 percent) had perianal, 6 (23 percent) enterocutaneous,
      3 (12 percent) rectovaginal, 4 (15 percent) peristomal, and 4 (15 percent) intra
      abdominal fistulas. Nineteen (73 percent) of the patients had had prior surgery
      for Crohn' s disease. Six patients (23 percent) had a complete response to
      infliximab with fistula closure, 12 (46 percent) had a partial response, and 8
      (31 percent) had no response to infliximab. Fourteen (54 percent) patients still
      required surgery for their fistulizing Crohn's disease after infliximab therapy
      (10 bowel resections, 4 perianal procedures), whereas half (6/12) of the patients
      treated with infliximab who still had open fistulas after treatment declined
      surgical intervention. Five of six patients with fistula closure on infliximab
      had perianal or rectovaginal fistulas. None of the patients with either
      enterocutaneous or peristomal fistulas were healed with infliximab. CONCLUSIONS:
      Although it was associated with a 61 percent complete or partial response rate,
      infliximab therapy did not supplant the need for surgical intervention in the
      majority of our patients with fistulizing Crohn's disease. Seventy-three percent
      of the patients either required surgery or still had open fistulas after
      infliximab therapy. Infliximab was much more effective in treating perianal
      disease than abdominal enterocutaneous disease.

PMID- 12072630
TI  - Diagnosing pouchitis: comparative validation of two scoring systems in routine
      follow-up.
AB  - PURPOSE: Pouchitis represents a serious threat to patients with ulcerative
      colitis after restorative proctocolectomy with ileal pouch-anal anastomosis. The
      frequency of pouchitis is high, and it implies the risk of pouch failure and the
      risk of malignant mucosal transformation in the pouch. Early detection and
      precise classification of the inflammatory process are required for adequate
      therapy, which might be facilitated using a scoring system. The aim of the
      present study was to validate two existing scoring systems in routine outpatient
      practice. METHOD: The Heidelberg Pouchitis Activity Score and the Pouchitis
      Disease Activity Index developed at the Mayo Clinic were simultaneously
      prospectively applied in a consecutive series of 103 outpatient consultations of
      41 patients at our hospital and comparatively validated against the diagnosis of
      " pouchitis" or "no pouchitis" concurrently made by a physician and a surgeon.
      RESULTS: The median score of examinations in which the clinicians' diagnosis was
      consistent with pouchitis were significantly higher than those of examinations
      inconsistent with pouchitis in both scoring systems (Heidelberg Pouchitis
      Activity Score, 17 (interquartile range, 14-21) and 8 (interquartile range, 5
      10), respectively, P < 0.001; Pouchitis Disease Activity Index, 7 (interquartile
      range, 5-8) and 2.5 (interquartile range, 1-4), respectively, P < 0.001). The
      sensitivity and specificity in the two total scores were 84 and 79.5 percent,
      respectively (Heidelberg Pouchitis Activity Score), and 60 and 96.2 percent,
      respectively (Pouchitis Disease Activity Index); in the field clinical
      manifestations 44 and 73.1 percent, respectively (Heidelberg Pouchitis Activity
      Score), and 20 and 87.2 percent, respectively (Pouchitis Disease Activity Index);
      in the field endoscopic manifestations 88 and 83.3 percent, respectively
      (Heidelberg Pouchitis Activity Score), and 60 and 89.7 percent, respectively
      (Pouchitis Disease Activity Index); and in the field histologic manifestations 72
      and 76.9 percent, respectively (Heidelberg Pouchitis Activity Score), and 44 and
      96.2 percent, respectively (Pouchitis Disease Activity Index). Lowering the
      cutoff point for diagnosis of pouchitis in the Pouchitis Disease Activity Index
      by 2 points (pouchitis: score >or= 5) would result in an 88 percent sensitivity
      and a 67 percent specificity. CONCLUSIONS: Specificity and sensitivity of the
      Heidelberg Pouchitis Activity Score were satisfactory. The cutoff point for
      diagnosing pouchitis in the Pouchitis Disease Activity Index would have to be
      lowered to reach an acceptable sensitivity and specificity. The very poor
      validity of the field clinical manifestations in diagnosing pouchitis emphasizes
      the need for endoscopic and histologic examination for detection of pouchitis.
      The issue of whether the diagnosis of pouchitis should be based on endoscopic and
      histologic features alone, instead of additionally taking clinical features into
      account, should be addressed in future studies.

PMID- 12072632
TI  - Double-blind, randomized trial comparing Harmonic Scalpel hemorrhoidectomy,
      bipolar scissors hemorrhoidectomy, and scissors excision: ligation technique.
AB  - PURPOSE: The aim of this study was to compare the outcome of patients receiving
      hemorrhoidectomy using Harmonic Scalpel, bipolar scissors, and the conventional
      scissors excision-ligation technique. METHODS: Eighty-six patients with
      irreducible prolapsing piles were randomly assigned to receive 1) Milligan-Morgan
      hemorrhoidectomy using scissors excision-ligation technique or 2) bipolar
      scissors hemorrhoidectomy and Harmonic Scalpel hemorrhoidectomy. Neither the
      patient nor the independent assessor were aware of the technique used at
      operation. Patients were followed up at 4 and 12 weeks after operation. The
      measured outcomes included 1) operation time; 2) blood loss; 3) postoperative
      hospital stay; 4) pain score; 5) pain expectation score; 6) date of first bowel
      movement; 7) number of pethidine injections; 8) number of dologesic tablets
      taken; 9) time off work or normal activity; 10) wound healing; 11) satisfaction
      score; and 12) postoperative complications, including anal stenosis and fecal or
      flatus incontinence. RESULTS: There was no difference among the three groups in
      the operation time, hospital stay, pain expectation score, day of first bowel
      movement, number of dologesic tablets taken, time off work or normal activity,
      wound healing, and satisfaction score. The complication rate also did not differ
      in the three groups. Both Harmonic Scalpel hemorrhoidectomy and bipolar scissors
      hemorrhoidectomy were superior to Milligan-Morgan hemorrhoidectomy in terms of
      reduced blood loss. Harmonic Scalpel hemorrhoidectomy had the best pain score
      when compared with bipolar scissors hemorrhoidectomy and Milligan-Morgan
      hemorrhoidectomy, and patients required significantly less pethidine injection
      after Harmonic Scalpel hemorrhoidectomy than after Milligan-Morgan
      hemorrhoidectomy. Although the time required to return to work or normal activity
      remained similar, patients after Harmonic Scalpel hemorrhoidectomy had the best
      satisfaction score among the three groups. CONCLUSION: The study shows that
      Harmonic Scalpel hemorrhoidectomy is as good as bipolar scissors hemorrhoidectomy
      in terms of reduced blood loss but is superior because it is associated with less
      postoperative pain and hence, better patient satisfaction. However, these
      observed benefits are small, and the time off work or normal activity remains
      similar.

PMID- 12072633
TI  - Surgical management of isolated retroperitoneal recurrences of colorectal
      carcinoma.
AB  - PURPOSE: Isolated locoregional disease accounts for approximately 20 percent of
      recurrences after treatment for colorectal cancer. It has been suggested that
      complete resection of these recurrences can result in increased survival. The
      value of surgery for isolated retroperitoneal recurrences has not been well
      defined. We have sought to characterize outcome and survival in patients
      undergoing resection for isolated retroperitoneal recurrences of colorectal
      cancer. METHODS: From a prospective database, 25 patients were identified as
      having undergone surgical exploration with curative intent for isolated
      retroperitoneal recurrences of colorectal cancer between 1988 and 1999. Variables
      studied included age, gender, location and size of the tumor, extent of
      resection, disease-free interval, and morbidity and mortality. Statistical
      analyses were performed using the log-rank test and Kaplan-Meier estimates, with
      overall survival as the primary end point. RESULTS: The study population
      consisted of 25 patients (13 males), with a median age of 55 years and a median
      follow-up of 29 (range, 1-151) months. The median time to first retroperitoneal
      recurrence was 23 (range, 3-72) months. Twenty patients underwent resection,
      whereas five patients were deemed unresectable at the time of operation. The
      median survival in patients who underwent resection patients was 31 months
      compared with 3 months in those patients who did not undergo resection (P =
      0.0001). Analysis of the entire group demonstrated a disease-free interval of
      greater than 24 months to be a positive predictor of outcome (median survival, 30
      vs. 48 months; P = 0.02). For patients undergoing resection, the presence of
      positive margins (P = 0.01) and tumor size >or=5 cm (P = 0.008) predicted a worse
      prognosis. In patients who underwent resection, the two-year and five-year
      overall survival rates were 60 and 15 percent, respectively. CONCLUSIONS:
      Patients with isolated retroperitoneal recurrences of colorectal cancer generally
      have a poor prognosis. However, a longer disease-free interval, complete negative
      margin resection, and smaller tumor size are associated with long-term survival
      in selected patients.

PMID- 12072634
TI  - The changing paradigm for the treatment of colonic hemorrhage: superselective
      angiographic embolization.
AB  - PURPOSE: Colonic bleeding has historically been controlled by the use of
      localization procedures and surgery. Since our initial experience with
      superselective embolization of colonic bleeding, it has become our preferred
      method for the control of lower gastrointestinal hemorrhage. This follow-up study
      evaluates the Hartford Hospital experience using angiographic methods as the
      primary modality for the treatment of colonic bleeding. METHODS: From March 1993
      to September 1999, 27 patients who had angiographically visualized colonic
      hemorrhage underwent arterial embolization procedures. Diagnostic arteriography
      was performed in all patients using digital subtraction imaging and selective
      contrast injections into the superior and inferior mesenteric arteries. Once the
      bleeding site was identified, superselective arteriogram and embolization was
      performed. Platinum-fibered coils, Hilal coils, or polyvinyl alcohol particle
      emboli were then fluoroscopically guided into the bleeding vessel. A repeat
      arteriogram was performed to confirm occlusion and the absence of any collateral
      channels. RESULTS: All 27 patients were initially controlled with arterial
      embolization; 6 patients rebled (22.2 percent), and 5 of these patients required
      surgery. Two patients demonstrated ischemia (7.4 percent), one of which required
      surgical intervention. The other patient was followed up by colonoscopy. There
      was no mortality in this study. CONCLUSION: Superselective embolization is
      effective in controlling colonic hemorrhage and is associated with a low rate of
      postembolization ischemia. Our experience with angiography reinforces the
      paradigm shift from its use as a diagnostic tool to the primary method for the
      control of colonic bleeding. Because patients have been followed up for as long
      as seven years, this approach remains effective for the long-term treatment of
      colonic bleeding.

PMID- 12072635
TI  - Long-term efficacy of dynamic graciloplasty for fecal incontinence.
AB  - PURPOSE: Patients with end-stage fecal incontinence in whom all standard medical
      and surgical treatment has failed or is not expected to be effective can be
      treated by dynamic graciloplasty. The aim of this study was to review the long
      term efficacy data. METHODS: Success was defined as a greater than 50 percent
      decrease in the frequency of incontinent episodes. Measured physiologic
      parameters included enema retention time and the difference in resting and
      squeezing pressures with and without stimulation. Measured quality-of-life
      parameters included the Medical Outcomes Study Short Form 36 Health Status
      Questionnaire, a Fecal Incontinence TyPE Specification, the Zung Self-Rating
      Depression Scale, the "state" portion of the State-Trait Anxiety Inventory, and
      the Visual Analog Scale, which were administered at baseline and through follow
      up. Independent monitors collected data as part of a multicenter trial for
      patients who underwent dynamic graciloplasty from May 1993 to November 1999.
      RESULTS: There were 129 patients entered in the study, 115 of whom met
      eligibility criteria and were included in the efficacy outcome analysis. Twenty
      seven patients entered the study with a preexisting functioning stoma; the
      remaining 88 patients did not have a functioning stoma at the time of enrollment.
      Success was achieved in 62 percent of nonstoma patients at 12 months; these
      results were sustained at 18-month and 24-month follow-up assessments (55 and 56
      percent, respectively). The success rate in the stoma patients increased from
      37.5 percent (9 of 24 patients) at 12 months to 62 percent (13 of 21 patients) at
      18 months and was 43 percent at 24 months (9 of 21 patients), which reflects the
      increased number of patients whose stomas were closed. Although the measured
      physiologic continence parameters generally improved, these changes did not
      correlate with continence outcome. The group of patients (stoma and nonstoma) who
      underwent dynamic graciloplasty showed statistically significant improvements in
      quality of life as measured by Medical Outcomes Study Short Form 36 physical
      function (P = 0.006) and social functioning (P = 0.02) assessment. CONCLUSIONS:
      Dynamic graciloplasty was successful in the majority of patients with end-stage
      fecal incontinence. This result was usually achieved by 12 months after surgery
      in patients who did not have stomas and by 18 months in patients who had stomas
      at the time of dynamic graciloplasty surgery. These various improvements
      conferred by dynamic graciloplasty persisted during the two-year follow-up.

PMID- 12072636
TI  - Effect of mucosal immunomodulation with fed cholera toxin on healing of
      experimental colonic anastomosis.
AB  - PURPOSE: The aim of this study was to investigate in rats whether preoperative
      orogastric administration of low doses of cholera toxin would influence the
      mechanical strength of experimental colonic anastomosis on the basis of the gut
      mucosal immunomodulation effect of this antigen. METHODS: The cholera toxin group
      (n = 14) was fed 10 microg of cholera toxin in phosphate-buffered saline three
      times before surgery at 10-day intervals, whereas the controls (n = 14) received
      phosphate-buffered saline only. Twenty-four hours after the last dose of cholera
      toxin (or placebo in control group), the animals underwent left colonic
      transection and anastomosis. Seven days after colonic transection-anastomosis,
      the bursting pressure of the anastomotic segment was recorded in situ.
      Perianastomotic and extra-anastomotic tissue samples were obtained for
      measurements of tissue transforming growth factor-beta, interleukin-6, and
      interferon-gamma levels with enzyme-linked immunosorbent assay. RESULTS: Cholera
      toxin administration resulted in a significantly higher bursting pressure than in
      the control group (165.78 +/- 12.37 vs. 138.4 +/- 7.87 mmHg; P < 0.001). Compared
      with the control group, the heightened mechanical strength of colonic anastomosis
      provided by cholera toxin was associated with significant increases in the
      perianastomotic tissue levels of transforming growth factor-beta (199.34 +/-
      24.85 vs. 70.66 +/- 10.63 pg/ml; P < 0.001) and interleukin-6 (439.31 +/- 95.14
      vs. 289.57 +/- 96.59 pg/ml; P = 0.001), whereas interferon-gamma was
      significantly lower (174.04 +/- 44.82 vs. 219.00 +/- 31.35 pg/ml; P < 0.05). This
      cytokine pattern induced by cholera toxin in the wound milieu was also found to
      be similar in the extra-anastomotic colon. CONCLUSION: The mechanical strength of
      uncomplicated experimental colonic anastomosis increased significantly with gut
      mucosal immunomodulation with repeated low preoperative doses of cholera toxin.
      This enhanced healing had significant positive correlation with the colonic
      tissue level of transforming growth factor-beta and inverse correlation with
      interferon-gamma. If the relevant dose regimen is identified and its safety is
      assured in humans, gut mucosal immunomodulation might provide an efficient, safe,
      and inexpensive tool to improve surgical outcome in colorectal surgery,
      particularly in high-risk situations.

PMID- 12072637
TI  - Retroperitoneal sepsis complicating stapled hemorrhoidectomy: report of a case
      and review of the literature.
AB  - Stapled hemorrhoidectomy (mucosectomy) is a new technique that has recently been
      introduced for the treatment of third-degree and fourth-degree hemorrhoids and
      rectal mucosal prolapse. We present a case of severe retroperitoneal sepsis
      complicating stapled hemorrhoidectomy that was successfully treated by
      conservative means, further surgery therefore being avoided. The literature on
      the more serious complications associated with stapled hemorrhoidectomy is
      reviewed.

PMID- 12072638
TI  - Aortic thrombosis after low anterior resection for rectal cancer: report of a
      case.
AB  - Pelvic surgery for malignant disease has been associated with numerous acute
      postoperative complications. These complications are primarily vascular or
      neurologic in origin. Several factors associated with the occurrence of these
      complications include the lithotomy position, the prolonged use of sequential
      compression devices, the use of certain types of stirrups, the presence of
      peripheral vascular disease, and the common hypercoagulable state of most cancer
      patients. We report for the first time a case of aortic thrombosis after elective
      low anterior resection for rectal cancer and discuss some factors that may have a
      role in the occurrence of this devastating complication.

PMID- 12072639
TI  - Giant fecaloma with idiopathic sigmoid megacolon: report of a case and review of
      the literature.
AB  - PURPOSE: Fecal impaction is a common condition, and " fecaloma" is an extreme
      variety of impaction. This is a report of a giant, solitary, and stubborn
      fecaloma not responding to nonoperative management. A surgical intervention for
      uncomplicated fecal impaction is rarely needed and reported in the literature.
      METHOD: A 39-year-old male patient with constipation presented with a firm,
      mobile, abdominal mass of six-months duration. Investigations revealed an
      isolated, giant fecaloma in a redundant sigmoid megacolon. After all the
      conservative measures were unsuccessful in evacuating the stubborn impaction, he
      was treated by sigmoid colectomy and primary anastomosis. CONCLUSION: A timely
      surgical intervention in recalcitrant fecal impactions may prevent possible
      stercoral ulcer perforation with a high mortality.

PMID- 12072640
TI  - Reconstruction of the pelvic floor using the rectus abdominis muscles after
      radical pelvic surgery.
AB  - PURPOSE: To support the small intestine out of the pelvic cavity, many methods
      have been described to reconstruct the pelvic floor after radical pelvic surgery.
      I describe a new technique using the rectus abdominis muscles for pelvic floor
      reconstruction. METHODS: The posterior rectus sheath and peritoneum are opened.
      The rectus muscles are exposed at both sides and they are divided between paired
      clamps at the level of the umbilicus. Then, the rectus muscles are carefully
      retracted downward, and the edges are sutured posteriorly to the promontorium and
      laterally around the linea terminalis. RESULTS: This method was used in 11
      patients who underwent radical pelvic surgery. Seven of 11 patients had radiation
      therapy started 4 weeks postoperatively. The patients were followed up for two
      years. No patient showed any complication such as adhesive obstruction of the
      bowel or radiation enteritis, even in the patients who underwent radiotherapy.
      CONCLUSIONS: Reconstruction of the pelvic floor using the rectus abdominis
      muscles after radical pelvic surgery is an easy and safe technique that avoids
      complications and serves as a barrier to radiation injury. Therefore, we believe
      that this method is a promising proposal requiring further investigation in a
      larger number of patients.

PMID- 12072642
TI  - Level of classification performance of KESS (symptom scoring system for
      constipation) validated in a prospective series of 105 patients.

PMID- 12072643
TI  - Indomethacin-induced rectovaginal fistula in a postpartum patient.

PMID- 12072645
TI  - Crystal-cell interaction in the pathogenesis of kidney stone disease.
AB  - PURPOSE OF REVIEW: Renal stone formation depends not so much on the formation of
      crystals, but on their retention in the kidney. Evidence has emerged that crystal
      retention is caused predominantly by the adherence of crystals to the epithelial
      cells lining the renal tubules. Understanding the mechanisms involved in crystal
      retention could lead to new therapeutic approaches for interfering with the renal
      stone-forming process in patients. Cell-culture studies have been performed to
      obtain insights into the susceptibility of the cell surface to crystal
      attachment, and to uncover cell-surface crystal-binding molecules. This review
      aims to put the relevant publications of the last decade in perspective. RECENT
      FINDINGS: Crystal-cell interaction has been investigated by using various renal
      tubular cell types in culture. Such studies have yielded several candidate
      crystal-binding molecules, including phosphatidylserine, sialic acid, collagen
      IV, osteopontin and, recently, hyaluronan. SUMMARY: Here, the results obtained in
      crystal-binding studies are recapitulated, compared and evaluated. Arguments are
      provided in support of the view that many of the proposed crystal-binding
      molecules could be linked in the series of events resulting in crystal retention.
      Under pathological conditions, pericellular matrices rich in the polysaccharide
      hyaluronan are proposed as the key binding substance for crystals at the surface
      of renal tubular cells.

PMID- 12072644
TI  - Renal colic: new concepts related to pathophysiology, diagnosis and treatment.
AB  - PURPOSE OF REVIEW: To give new insights into the pathophysiology, diagnosis and
      treatment of acute renal colic caused by a stone disease. RECENT FINDINGS:
      Traditional intravenous pyelography is no longer the primary method of
      investigation in patients with renal colic. If the patient has a history of
      previous attacks of renal colic and stone disease the recommended diagnostic
      approach is to start with plain abdominal radiography and ultrasonography
      together with Doppler ultrasonography. Noncontrast computerized tomography is
      reserved for unsolved problems. If the patient has no history of stone disease or
      has atypical clinical presentation it is better to start with noncontrast
      computerized tomography. Intravenous pyelography is indispensable if an
      endoscopic or open intervention is required. Magnetic resonance imaging is a
      promising method of investigation, particularly in pregnant women. Effective pain
      relief is achieved by the use of opioids, nonsteroidal antiinflammatory drugs or
      desmopressin. SUMMARY: The diagnostic approach to renal colic has recently been
      changed due to the introduction of new, noninvasive radiologic procedures such as
      Doppler ultrasonography, noncontrast computerized tomography and magnetic
      resonance imaging.

PMID- 12072646
TI  - Expanding role of ureteroscopy and laser lithotripsy for treatment of proximal
      ureteral and intrarenal calculi.
AB  - PURPOSE OF REVIEW: Ureteroscopy has assumed an expanded and important role in the
      treatment of proximal ureteral and intrarenal calculi with the development of new
      endoscopes, more effective grasping devices, and the holmium laser lithotriptor.
      RECENT FINDINGS: The success rate for treating proximal ureteral stones with
      small rigid and flexible ureteroscopes and the holmium laser is well over 90%.
      Lower pole renal calculi can also be treated with a success rate of approximately
      80%, which surpasses that of shock wave lithotripsy. Selected stones that are
      over 2 cm in diameter, along with branched stones, can also be treated
      successfully with ureteroscopy. SUMMARY: Ureteroscopy is the most successful
      technique for the treatment of ureteral calculi (success rates >90%) and is an
      optional treatment for many renal calculi.

PMID- 12072647
TI  - Is there a role for prophylactic shock wave lithotripsy for asymptomatic calyceal
      stones?
AB  - PURPOSE OF REVIEW: The tolerability of extracorporeal shock wave lithotripsy has
      led to an increase in the treatment of small, asymptomatic renal calculi, yet we
      know very little about the natural history of such stones or about the long-term
      effects of this treatment. The efficacy of extracorporeal shock wave lithotripsy
      has been called into question, especially for lower pole stones. Several recent
      clinical studies have addressed these issues as well as the natural history of
      residual stone fragments following extracorporeal shock wave lithotripsy. RECENT
      FINDINGS: Preliminary results of a randomized controlled trial show that
      prophylactic extracorporeal shock wave lithotripsy for small, asymptomatic renal
      calyceal stones does not appear to offer any advantage to patients in terms of
      stone-free rates, quality of life, renal function, symptoms, or hospital
      admissions, nor does it appear to affect blood pressure. However, a policy of
      observation is associated with a greater risk of requiring more invasive
      procedures. Reports regarding the incidence of hypertension following
      extracorporeal shock wave lithotripsy are conflicting, as are reports regarding
      anatomical factors affecting the clearance of lower pole stones. Percutaneous
      removal appears to be superior to extracorporeal shock wave lithotripsy for the
      treatment of lower pole stones. SUMMARY: Extracorporeal shock wave lithotripsy
      does not appear to improve the clinical outcome of patients with small,
      asymptomatic calyceal calculi. Longer follow-up is required to assess the
      validity of the preliminary findings and may shed light on the long-term effects
      of this technique on blood pressure and stone growth/recurrence. Anatomical
      factors affecting the clearance of lower pole stones require standardization and
      further study. Further in-vitro studies are required to study the kinetics of
      stone growth and the effects of urine composition, flow rate, and macromolecular
      components.

PMID- 12072648
TI  - Update on shock wave lithotripsy technology.
AB  - PURPOSE OF REVIEW: Since the first patient was successfully treated with
      extracorporeal shock wave lithotripsy in 1980, its rapid acceptance and
      widespread use have championed this form of stone therapy as the treatment of
      choice for the majority of renal and ureteral calculi. Worldwide clinical series
      have documented the efficacy and safety of shock wave lithotripsy. RECENT
      FINDINGS: Shock wave lithotripters have undergone modifications of the source for
      generation of shock waves, focusing, and even localization techniques since the
      introduction of the original Dornier HM3 lithotripter. Yet the basic concepts
      remain the same: to produce an acoustic wave that can be focused at a specific
      location for stone fragmentation. Safety and efficacy of the different
      generations of lithotripters is well documented. Indications and utilization of
      shock wave lithotripsy have expanded, with clinical efficacy approaching or
      exceeding that of other modalities of minimally invasive surgery. Complications,
      however, can arise as a result of shock wave therapy. SUMMARY: This review
      provides an update of the latest shock wave technology, reviewing the clinical
      indications and efficacy of treatment and discussing the potential adverse events
      associated with shock wave lithotripsy.

PMID- 12072649
TI  - The effect of rate of shock wave delivery on the efficiency of lithotripsy.
AB  - PURPOSE OF REVIEW: The potential mechanisms of a shock wave rate effect are
      reviewed here, together with a report on the results of in-vitro, in-vivo and
      clinical studies that have assessed the effect of altering the shock wave rate on
      stone breakage and tissue injury by shock wave lithotripsy. RECENT FINDINGS: The
      vast majority of studies assessing shock wave rate have reported improved stone
      fragmentation and a reduction in shock wave lithotripsy-induced tissue damage
      with slower rates of shock wave delivery. However, the optimal shock wave rate
      has not been determined. SUMMARY: Slower rates of shock wave lithotripsy appear
      to improve the efficiency of this approach and therefore this suggests the need
      for a randomized clinical trial to assess shock wave rate.

PMID- 12072650
TI  - Stones in urinary diversions: update on medical and surgical issues.
AB  - PURPOSE OF REVIEW: Patients who undergo urinary tract diversion are at an
      increased risk of urolithiasis for various reasons. The purpose of this article
      is to provide an up-to-date summary of the progress that has been made in the
      pathogenesis, diagnosis and treatment of stones in patients with urinary
      diversions. Finally, we will provide recommendations for follow-up in patients
      with urinary diversions who develop urinary tract calculi. RECENT FINDINGS: In
      contemporary studies, the incidence of urolithiasis in patients with urinary
      diversion appears to be decreasing. Computed tomography scanning has been shown
      to be superior to ultrasound in the diagnosis of calculi in such patients.
      Endourological procedures have become the mainstay of therapy for stones in
      patients with urinary diversions. Since the introduction of extracorporeal shock
      wave lithotripsy, percutaneous nephrolithotripsy and ureteroscopy, the need for
      open surgery has decreased, even in this anatomically unique and surgically
      challenging patient population. SUMMARY: Urolithiasis is an established long-term
      complication of urinary diversion. In recent years, significant advances have
      been made in the pathogenesis, diagnosis and treatment of such stones. As a
      result of potential stone-related complications, we recommend lifelong
      surveillance for all patients with urinary stones and diversions, with medical
      therapy when indicated, in order to minimize these complications.

PMID- 12072651
TI  - Laser lithotripsy.
AB  - PURPOSE OF REVIEW: All literature related to laser lithotripsy published within
      the past year was reviewed. Salient articles have been reviewed and grouped
      according to safety issues, efficacy, comparison studies, biliary applications or
      future directions. RECENT FINDINGS: There is no evidence of renal deterioration
      after holmium:yttrium-aluminium-garnet lithotripsy. Laser-related complications
      occur in less than 1%. Stone-free rates from holmium:yttrium-aluminium-garnet
      lithotripsy are greater than 90% for ureteral calculi, and 67-84% for renal
      calculi. This method of lithotripsy is effective for ureteral and renal calculi
      in morbidly obese patients who are not suitable candidates for shock-wave
      lithotripsy or percutaneous nephrolithotomy. Holmium:yttrium-aluminium-garnet
      lithotripsy is more effective than pneumatic lithotripsy for ureteral calculi,
      but no more effective than shock-wave lithotripsy (Dornier HM-3) for distal
      ureteral calculi. Holmium:yttrium-aluminium-garnet lithotripsy of biliary calculi
      is uniformly effective. Preliminary data showed the erbium:yttrium-aluminium
      garnet laser to be more efficient than holmium:yttrium-aluminium-garnet energy,
      but current erbium:yttrium-aluminium-garnet fibers are impractical. SUMMARY: The
      holmium:yttrium-aluminium-garnet laser is safe and effective. It is the
      lithotrite of choice for endoscopic ureteral and ureterorenoscopic lithotripsy.

PMID- 12072652
TI  - Non-neurogenic female voiding dysfunction.
AB  - PURPOSE OF REVIEW: The pathophysiological mechanisms of female voiding phase
      dysfunction are poorly understood, and there are neither standard definitions nor
      guidelines for diagnosis and treatment. The aim of this review is to present up
      to-date data and controversies associated with non-neurogenic female voiding
      dysfunction. RECENT FINDINGS: Conceptually, voiding phase dysfunction may have
      bladder or urethral causes. Bladder causes include detrusor contraction of
      inadequate magnitude or duration to effect bladder emptying (detrusor
      underactivity), or the absence of detrusor contraction (detrusor arreflexia).
      Urethral causes consist of bladder outlet obstruction as a result of urethral
      overactivity (functional obstruction), or anatomical (mechanical obstruction)
      pathologies. The specific prevalence and contribution of each of the above
      mechanisms is unknown. Furthermore, a correct and timely diagnosis may be
      difficult, because clinical features are very similar to those of other lower
      urinary tract symptoms, and diagnostic modalities are often inconclusive or even
      misleading. A full urodynamic evaluation is essential in making the diagnosis;
      however, standard urodynamic definitions are still lacking. In the following
      review, we will present recent findings associated with the prevalence, etiology
      and diagnosis of each of the different categories of female voiding phase
      dysfunction, and highlight new advances presented during the past year. SUMMARY:
      Further epidemiological and pathophysiological investigations are needed to
      evaluate the causes and main risk factors of voiding dysfunction in women. A
      better understanding of the pathophysiological mechanisms associated with this
      challenging condition may provide the possibility to use appropriate diagnostic
      and treatment modalities, thus avoiding unnecessary interventions.

PMID- 12072653
TI  - Nocturnal enuresis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight and comment upon
      important areas of enuresis research. RECENT FINDINGS: Current areas of
      pathophysiological focus are nocturnal urine production, in which alternative
      mechanisms other than deficient vasopressin secretion has been implicated in some
      patients. Bladder reservoir function has gained renewed interest, and has proved
      to be one of the best predictors of treatment response to desmopressin. Various
      aspects of central nervous system function, including arousability and pontine
      reflexes, are in focus, and molecular genetics has provided firm evidence of a
      link between enuresis and different chromosomal markers. The therapeutic focus is
      directed towards a differential approach based upon the underlying mechanism and
      towards combination therapies such as alarm devices and desmopressin as well as
      anticholinergic agents and desmopressin. Furthermore, new exciting treatment
      concepts such as laser acupuncture have shown promising results in initial
      studies. SUMMARY: Despite recent advances in our understanding of nocturnal
      enuresis, we are still far from understanding in detail this socially
      discomfiting and scientifically intriguing condition, and many controversies
      remain. However, the substantiation that enuresis is a heterogeneous condition
      that requires a differential approach has provided the basis for further
      progress.

PMID- 12072654
TI  - Interstitial cystitis: an update.
AB  - PURPOSE OF REVIEW: Interstitial cystitis is a chronically progressive, severely
      debilitating, heterogeneous syndrome affecting the urinary bladder, mainly
      associated with urgency, frequency and pain. Though known for over a century, its
      etiology is poorly understood and universally effective treatments are lacking.
      This review focuses on recently published literature on the disorder. RECENT
      FINDINGS: Appropriate diagnostic tests for interstitial cystitis remain
      uncertain. The diagnostic criteria developed by the US National Institutes of
      Health represent research definitions which are subject to controversial debate
      for their overenthusiastic clinical application. The diagnosis is made clinically
      and by cystoscopy with hydrodistention and sometimes biopsy when other
      pathologies have been excluded. In symptomatic patients, glomerulations upon
      bladder distension are indicative but not pathognomonic for nonulcerative
      interstitial cystitis. Patients with ulcerative disease represent a separate
      subgroup with distinct characteristics and treatment implications. The role of
      bladder permeability tests remains controversial. Promising noninvasive markers
      for interstitial cystitis have been described but are not yet clinically
      available. Validated symptom scores are appropriate to assist in diagnostics and
      to monitor disease course and treatment efficacy. Lately investigated hypotheses
      for causative factors include occult or resistant microorganisms, urothelial
      hyperpermeability, neurogenic or hormonal pathomechanisms, and mast cell
      activation. Increasing evidence for a genetic susceptibility is emerging.
      SUMMARY: Among the multitude of oral, intravesical, interventional and
      complementary treatments suggested few studies have high levels of evidence.
      Newly proposed agents must await further controlled studies. Treatment remains
      empiric until radical surgical procedures should ultimately be considered for
      severe refractory cases.

PMID- 12072655
TI  - Review of the available urethral bulking agents.
AB  - PURPOSE OF REVIEW: Newer tissue bulking agents used to treat stress urinary
      incontinence and vesicoureteral reflux provide for similar rates of success as
      older agents, but with greater safety and hopefully with greater durability. We
      review the new studies on the development and on the current trials of bulking
      agents. RECENT FINDINGS: Recent reports suggest that periurethral bulking agents
      are as effective for genuine stress urinary continence as for intrinsic sphincter
      deficiency, expanding the indications for injectable agents to include patients
      desiring less invasive procedures due to personal preference or as a result of
      medical necessity. Newer bulking agents, Durasphere and Macroplastique, appear
      safe and as efficacious as older agents in early trials. Durability remains a
      question for these agents. Injectable tissue matrices and autologous cells may
      prove useful in the future. SUMMARY: If durable and safe, these minimally
      invasive bulking agents may prove useful for all types of stress urinary
      incontinence. The price of minimal invasiveness may be lower efficacy, but their
      use does not compromise further therapy, should it be needed.

PMID- 12072656
TI  - Management of the urethral outlet in patients with severe prolapse.
AB  - PURPOSE OF REVIEW: Numbers of women seeking consultation for pelvic floor
      disorders, a large portion of which will involve pelvic organ prolapse (POP) and
      lower urinary tract dysfunction, are expected to reach epidemic proportions
      within the next decade. A full understanding of the complex impact of pelvic
      organ prolapse on lower urinary tract function is crucial to successful
      management. RECENT FINDINGS: Recent data lend support to the concept that women
      with POP, but no associated urethral dysfunction, may be best served by a
      surgical repair that carefully avoids dissection in the periurethral area.
      Conversely, preoperative evaluation will often reveal bladder outlet obstruction
      concomitant with 'hidden', 'potential', or 'occult' stress urinary incontinence
      when the prolapse is reduced. Many of these women will not have incontinence
      symptoms in daily life. Paradoxically, the mechanical bladder outlet obstruction
      may induce detrusor instability with subsequent obstructed/overactive bladder
      symptom complexes not dissimilar to those of men with prostatic bladder outlet
      obstruction. Anatomic research shows that the vessels and nerves supplying the
      urethra are particulary vulnerable to surgical techniques used in pelvic organ
      prolapse repair. SUMMARY: This mix of obstructed, overactive bladder with hidden
      stress incontinence increases with degree of POP, and all women with severe
      prolapse will fair best if evaluated for all three conditions prior to surgical
      repair.

PMID- 12072657
TI  - Evaluation and management of rectoceles.
AB  - PURPOSE OF REVIEW: As life expectancy increases, the prevalence of pelvic organ
      prolapse in general, and rectoceles, in particular, will continue to grow. The
      objectives of this article are to review the basic anatomy and contributing
      factors associated with the development of rectoceles and to discuss the
      appropriate work-up and treatment options. RECENT FINDINGS: The main themes in
      the current literature stress the importance of not only anatomic restoration,
      but also quality of life issues regarding visceral and sexual function when
      performing a rectocele repair. Many recent studies are also evaluating the role
      of preoperative adjunctive tests to better evaluate women with combined pelvic
      floor disorders, while others are looking at outcomes data regarding the various
      surgical approaches to repair a rectocele. SUMMARY: With significant advancements
      in pelvic anatomy over the last several decades the surgical approach to treating
      symptomatic rectoceles has evolved from the traditional posterior colporrhaphy
      with levator ani plication to the defect specific rectocele repair. While
      anatomic and overall functional outcomes have improved, one still needs to better
      define the correlation between defecatory dysfunction and a rectocele.

PMID- 12072658
TI  - Surgical management of the apical vaginal defect.
AB  - PURPOSE OF REVIEW: To review the etiology, presentation, imaging techniques and
      current surgical management of the apical vaginal defect. RECENT FINDINGS:
      Urologists are increasingly managing urinary incontinence and prolapse of the
      anterior and posterior compartment but most refer the management of the apical
      defect to gynecologists. A variety of abdominal and vaginal repairs are commonly
      utilized to repair the apical defect, often based on the surgeon's preference. Of
      the abdominal repairs, abdominal sacral colpopexy with mesh remains the gold
      standard. Laparoscopic techniques, although feasible, have not gained widespread
      acceptance. Of the vaginal restorative procedures there are proponents for
      uterosacral ligament vault suspension, iliococcygeus and sacrospinous ligament
      fixation. The uterosacral ligament vault suspension is the most anatomic of the
      repairs and hence least likely to create a predisposition to future anterior or
      posterior vaginal wall defects or compromise vaginal function. In rare instances
      where restorative procedures are discouraged and sexual function is no longer
      desired, obliterative procedures, which are better tolerated, may be more
      appropriate. SUMMARY: The best approach for restoration of vaginal apical support
      remains controversial with abdominal and vaginal routes commonly utilized. A
      single approach or procedure based on the surgeon's preference is not always
      optimal. Procedure selection should be individualized based on the patient's age,
      comorbidities, prior surgical history and level of physical and sexual activity.
      The transvaginal uterosacral ligament vaginal vault suspension is increasingly
      our procedure of choice for management of the apical defect due to its
      versatility, reduced postoperative morbidity and excellent short-term results.

PMID- 12072659
TI  - Acid suppression in a critical care environment: state of the art and beyond.

PMID- 12072660
TI  - Pathophysiology of the upper gastrointestinal tract in the critically ill
      patient: rationale for the therapeutic benefits of acid suppression.
AB  - Gastric mucosal damage occurs in critically ill patients in intensive care units
      and develops in the setting of severe physiologic stress. Within 24 hrs of
      admission to the intensive care unit, 75% to 100% of critically ill patients
      demonstrate evidence of stress-related mucosal disease. Stress ulcers present a
      risk of clinically important bleeding, which is associated with alterations in
      physiology, such as hypotension or tachycardia, or results in anemia or the need
      for transfusion. Clinically important bleeding occurs in approximately 1% to 4%
      of critically ill patients. The pathophysiology of stress-related mucosal disease
      is complex. Major factors responsible for stress ulcer are decreased blood flow,
      mucosal ischemia, and hypoperfusion and reperfusion injury. Acid-suppressive
      regimens that elevate the intragastric pH and maintain the pH over time have the
      potential to prevent stress-related mucosal disease. Intragastric pH studies have
      demonstrated that, whereas a pH of >4 may be adequate to prevent stress
      ulceration, a pH of >6 may be necessary to maintain clotting in patients at risk
      of rebleeding from peptic ulcer. Studies comparing the ability of intravenous
      administrations of histamine-2-receptor antagonists and proton pump inhibitors to
      raise and maintain intragastric pH suggest that, although both can raise the pH
      to >4, proton pump inhibitors are much more likely to maintain this pH. Unlike
      histamine-2-receptor antagonists, proton pump inhibitors can elevate and maintain
      the intragastric pH at >6. This is relevant for patients in the intensive care
      unit at risk for rebleeding from peptic ulcers after hemostasis.

PMID- 12072661
TI  - Pharmacology of acid suppression in the hospital setting: focus on proton pump
      inhibition.
AB  - The more potent and longer-lasting inhibition of gastric acid secretion provided
      by proton pump inhibitors (PPIs) as compared with histamine-2-receptor
      antagonists is caused in large part by differences in their mechanism of action.
      PPIs block histamine-2-, gastrin-, and cholinergic-mediated sources of acid
      production and inhibit gastric secretion at the final common pathway of the H+/K+
      adenosine triphosphatase proton pump. In contrast, histamine-2-receptor
      antagonists cannot block receptor sites other than those mediated by histamine.
      It seems that the rapid loss of acid suppression activity by the histamine-2
      receptor antagonists may be attributed to tolerance. Such tolerance has not
      occurred in patients receiving PPIs because these agents are irreversible
      inhibitors of the H+/K+ adenosine triphosphatase proton pump. For these reasons,
      patients who have acid-related disorders that require high levels of acid
      suppression do not respond well to intravenous histamine-2-receptor antagonists
      and would be excellent candidates for intravenous PPI therapy. Candidates for
      intravenous PPIs also include patients who cannot receive oral PPIs and those who
      may need the higher acid suppression therapy provided by the intravenous rather
      than the oral route. Clinical studies have demonstrated the efficacy of
      intravenous pantoprazole in maintaining adequate control of gastric acid output
      during the switch from oral to intravenous therapy in patients with severe
      gastroesophageal reflux disease or the Zollinger-Ellison syndrome. Intragastric
      administration of solutions prepared from oral PPIs has been used as an
      alternative to the intravenous route in critical care settings. However,
      decreased bioavailability may limit the value of intragastric delivery of PPIs
      because of the high frequency of gastric emptying problems in critically ill
      patients.

PMID- 12072662
TI  - Stress-related mucosal disease in the critically ill patient: risk factors and
      strategies to prevent stress-related bleeding in the intensive care unit.
AB  - Stress-related mucosal disease develops in patients in the intensive care unit
      and can result in clinically important bleeding, which is associated with
      increased mortality. Patients in the intensive care unit without either
      mechanical ventilation or coagulopathy, which are the primary risk factors for
      such bleeding, do not seem to need or to benefit from prophylactic acid
      suppression for stress-related mucosal disease. Although histamine-2-receptor
      antagonists significantly reduce clinically important bleeding in patients in the
      intensive care unit and are widely used for prophylaxis, their benefits are
      limited by the rapid development of tolerance. Previous data suggested that
      agents that elevate the intragastric pH may increase the susceptibility of
      patients in the intensive care unit to nosocomial pneumonia. However, the largest
      study to date showed that intravenous histamine-2-receptor antagonists may not
      significantly increase the risk of ventilator-associated pneumonia or mortality
      compared with sucralfate, an agent that does not affect intragastric pH.
      Intravenous proton pump inhibitors are more potent and longer-acting inhibitors
      of gastric acid production than intravenous histamine-2-receptor antagonists. The
      ability of proton pump inhibitors to prevent stress-related mucosal disease and
      clinically important bleeding seems to be clinically meaningful. Preliminary
      findings have shown that intermittent administration of intravenous pantoprazole,
      the first proton pump inhibitor available by this route in the United States, is
      as effective in raising intragastric pH on the first day as a continuous infusion
      of a histamine-2-receptor antagonist in clinical trials conducted within an
      intensive care unit setting. This suggests that for stress ulcer prophylaxis,
      intermittent dosing with an intravenous proton pump inhibitor may be an
      alternative to high-dose continuous infusions of a histamine-2-receptor
      antagonist. These agents must be compared in clinical trials conducted in an
      intensive care unit setting.

PMID- 12072663
TI  - Acute upper gastrointestinal bleeding in critically ill patients: causes and
      treatment modalities.
AB  - Upper gastrointestinal bleeding from peptic ulcers or other nonvariceal causes
      generally stops spontaneously; if it fails to do so, aggressive management is
      required. Such measures also are necessary for patients at high risk for
      rebleeding. Endoscopic therapy achieves hemostasis in >90% of bleeding patients
      and reduces mortality. After successful hemostasis of the initial bleeding
      episode, the primary concern becomes the prevention of rebleeding, which occurs
      in up to 20% of patients. Acid suppression with histamine-2-receptor antagonists
      has been widely used for many years to prevent recurrent bleeding. However, in
      acutely bleeding patients, these agents have not been shown to reduce the number
      of episodes of further bleeding or rebleeding or to reduce the need for
      transfusions or surgery. Omeprazole, an intravenous proton pump inhibitor,
      significantly reduced the rate of rebleeding in a recent placebo-controlled trial
      in which only patients with endoscopic confirmation of successful hemostasis were
      enrolled. Although this drug does not seem to reduce the need for surgical
      intervention or to decrease mortality, the trial does indicate the promise of
      intravenous proton pump inhibitors in reducing upper gastrointestinal bleeding.
      Evidence from additional well-controlled trials is needed to confirm this
      finding. The use of proton pump inhibitors in this setting also may have a
      positive economic impact, and a decrease in the percentage of patients who
      experience rebleeding will eliminate the cost of further management strategies in
      those cases.

PMID- 12072664
TI  - Intravenous proton pump inhibitors in the critical care setting.
AB  - Two well-controlled trials were carried out to investigate the effectiveness of
      intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after
      successful hemostasis. The results demonstrated that the PPI reduced the rate of
      rebleeding significantly. The recent availability of the first intravenous PPI
      formulation in the United States, intravenous pantoprazole, represents an
      alternative to intravenous histamine-2 receptor antagonists. The results of 16
      randomized, controlled trials involving a total of >3,800 patients (1,892
      receiving PPIs and 1,911 controls) suggest that bolus administration plus
      continuous infusion of PPIs is a more effective pharmacotherapy than bolus
      infusion alone in decreasing both rebleeding and the need for surgery. Optimal
      effect is achieved with an intravenous 80-mg bolus, followed by continuous
      infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral
      PPI. Intermittent bolus administration yielded a minimal benefit. A difference in
      mortality rates has not yet been demonstrated.

PMID- 12072665
TI  - Evidence-based medicine as it applies to acid suppression in the hospitalized
      patient.
AB  - An evidence-based-medicine approach may be applied to studies in the medical
      literature to help physicians make sound judgments about efficacy and safety data
      and to improve clinical decision making. To assess the role of gastric acid
      suppression in the prevention of stress ulcer bleeding and in the management of
      upper gastrointestinal bleeding after successful hemostasis of bleeding peptic
      ulcer disease, the following questions should be addressed: Is it possible to
      identify risk factors for clinically important bleeding in critically ill
      patients? Can intravenous acid suppression prevent stress ulcer-related bleeding
      or prevent rebleeding in peptic ulcers after successful hemostasis? What is the
      most effective method of acid suppression for these disorders? An evidence-based
      medicine review of published trials yields sufficient evidence to support the use
      of prophylactic acid suppression in critically ill patients with coagulopathy or
      in those who are receiving prolonged mechanical ventilation. Not enough data have
      accumulated to prove the superiority of intravenous proton pump inhibitors to
      intravenous histamine-2-receptor antagonists for prophylaxis of clinically
      important stress ulcer bleeding. With respect to acute gastrointestinal bleeding,
      however, two well-conducted trials indicate that an intravenous proton pump
      inhibitor is significantly more effective than an intravenous histamine-2
      receptor antagonist or placebo in reducing the rate of rebleeding after
      hemostasis in patients with bleeding peptic ulcer. Analysis of the data from both
      trials shows that only five to six patients would need to receive an intravenous
      proton pump inhibitor to avoid one episode of rebleeding.

PMID- 12072666
TI  - Acute abdomen in the medical intensive care unit.
AB  - OBJECTIVE: Acute abdominal complication in the medical intensive care unit may be
      underdiagnosed and can add significant risk of death. We hypothesize that delays
      in surgery because of atypical presentation, such as the absence of peritoneal
      signs, may contribute to mortality. DESIGN: Retrospective cohort study (1995
      2000). SETTING: Medical intensive care unit in a tertiary care center. PATIENTS:
      Medical intensive care unit patients with clinical, surgical, or autopsy
      diagnosis of acute abdominal catastrophe (gangrenous or perforated viscus).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients (1.3%)
      met inclusion criteria. Ischemic bowel was the most common diagnosis, followed by
      perforated ulcer, bowel obstruction, and cholecystitis. Actual mortality rate was
      higher than predicted by Acute Physiology and Chronic Health Evaluation (APACHE)
      III scores at the time of medical intensive care unit admission (63% vs. 31%).
      Twenty-six patients (34%) did not have surgery, and none of these survived. Fifty
      one patients underwent surgery and 28 survived (56%). Delay in surgical
      evaluation (p <.01) and intervention (p <.03), APACHE III scores (p <.01), renal
      insufficiency (p <.01), and a diagnosis of ischemic bowel (p <.01) were
      associated with increased mortality rates. Surgical delay was more likely to
      occur in patients with altered mental state (p <.01), no peritoneal signs (p
      <.01), previous opioids (p <.03), antibiotics (p <.02), and mechanical
      ventilation (p <.02). CONCLUSION: Delays in surgical evaluation and intervention
      are critical contributors to mortality rate in patients who develop acute
      abdominal complications in a medical intensive care unit.

PMID- 12072667
TI  - Cost effectiveness of aggressive care for patients with nontraumatic coma.
AB  - OBJECTIVE: To estimate the cost effectiveness of aggressive care for patients
      with nontraumatic coma. DESIGN: Cost-effectiveness analysis. SETTING: Five
      academic medical centers. PATIENTS: Patients with nontraumatic coma enrolled in
      the Study to Understand Prognoses and Preferences for Outcomes and Risks of
      Treatments (SUPPORT). Patients with reversible metabolic causes of coma such as
      diabetic ketoacidosis or uremia were excluded. MEASUREMENTS: We calculated the
      incremental cost effectiveness of continuing aggressive care vs. withholding
      cardiopulmonary resuscitation and ventilatory support after day 3 of coma. We
      estimated life expectancy based on up to 4.6 yrs of follow-up. Utilities (quality
      of-life weights) were estimated using time-tradeoff questions. Costs were based
      on hospital fiscal data and Medicare data. Separate analyses were conducted for
      two prognostic groups based on five risk factors assessed on day 3 of coma: age >
      or = 70 yrs, abnormal brainstem response, absent verbal response, absent
      withdrawal to pain, and serum creatinine > or = 132.6 micromol/L (1.5 mg/dL).
      RESULTS: For the 596 patients studied, the median (25th, 75th percentile) age was
      67 yrs (range, 55-77), and 52% were female. By 2 months after enrollment, 69% had
      died, 19% were severely disabled, 7% had survived without severe disability, and
      4% had survived with unknown functional status. The incremental cost
      effectiveness of the more aggressive care strategy was $140,000 (1998 dollars)
      per quality-adjusted life year (QALY) for high-risk patients (3-5 risk factors,
      93% 2-month mortality) and $87,000/QALY for low-risk patients (0-2 risk factors,
      49% mortality). In sensitivity analyses, the incremental cost per QALY did not
      fall below $50,000/QALY, even with wide variation in our baseline estimates.
      CONCLUSIONS: Continuing aggressive care after day 3 of nontraumatic coma is
      associated with a high cost per QALY gained, especially for patients at high risk
      for poor outcomes. Earlier decisions to withhold life-sustaining treatments for
      patients with very poor prognoses may yield considerable cost savings.

PMID- 12072668
TI  - Pulmonary artery occlusion pressure estimation: how confident are
      anesthesiologists?
AB  - OBJECTIVE: The pulmonary artery catheter is a controversial device, and
      randomized evaluation of its effectiveness has been demanded. Accurate estimation
      of pulmonary artery occlusion pressure is important for optimal use of the
      pulmonary artery catheter. Anesthesiologists use the pulmonary artery catheter
      frequently but have not been surveyed about confidence in pulmonary artery
      occlusion pressure estimation. Our objective was to determine the ability of
      practicing cardiovascular anesthesiologists to estimate pulmonary artery
      occlusion pressure accurately and measure their confidence in this estimate.
      DESIGN: Cross-sectional survey. SETTING: All academic and community hospitals in
      English-speaking Eastern Canada and selected centers in Western Canada and the
      United States. PATIENTS: Cardiovascular anesthesiologists. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: We measured agreement with expert-defined timing
      of pulmonary artery occlusion pressure estimation, estimation of a sample
      pulmonary artery occlusion pressure trace, and management of a hypothetical
      clinical complication (air embolism). Seventy-seven percent of 345
      anesthesiologists responded. Agreement about the optimal timing of pulmonary
      artery occlusion pressure estimation (89%) and the management of air embolism
      (85%) was near expectations (expected 90%). However, the pulmonary artery
      occlusion pressure waveform was interpreted accurately by only 61%, whereas 28%
      disagreed and 11% were uncertain. Significant positive associations (p =.016)
      between continuing medical education items and accurate interpretation were
      observed. CONCLUSIONS: Estimation of a sample pulmonary artery occlusion pressure
      trace by practicing anesthesiologists was in only modest agreement with expert
      assessment and published standards. Anesthesiologists demonstrated substantially
      less confidence in pulmonary artery occlusion pressure estimation than in the
      optimal timing of pulmonary artery occlusion pressure estimation. Before the
      effectiveness of the pulmonary artery catheter in clinical care can be
      systematically assessed, efforts are needed to enhance accuracy and consistency
      of pulmonary artery occlusion pressure estimation.

PMID- 12072669
TI  - Selective decontamination of the digestive tract to prevent postoperative
      infection: a randomized placebo-controlled trial in liver transplant patients.
AB  - OBJECTIVE: To determine the efficacy of selective decontamination of the
      digestive tract (SDD) in patients undergoing elective transplantation of the
      liver. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Two
      academic teaching hospitals. PATIENTS: Adult patients undergoing elective liver
      transplantation: 26 patients receiving SDD and 29 patients receiving a placebo.
      INTERVENTIONS: Patients undergoing SDD were administered 400 mg of norfloxacin
      once daily as soon as they were accepted for transplantation. Postoperative
      treatment for this group consisted of 2 mg of colistin, 1.8 mg of tobramycin, and
      10 mg of amphotericin B, four times daily, combined with an oral paste containing
      a 2% solution of the same drugs until postoperative day 30. Prophylactic
      intravenous administration of antibiotics was not part of the SDD regimen in this
      study. Control patients were given a similar regimen with placebo drugs.
      MEASUREMENTS: The mean number of postoperative bacterial and fungal infections in
      the first 30 days after transplantation was the primary efficacy end point. Days
      on a ventilator, days spent in the intensive care unit, and medical costs were
      registered as secondary outcome variables. MAIN RESULTS: Of the 26 patients
      undergoing SDD, 22 (84.5%) developed an infection in the postoperative study
      period; in the placebo group (n = 29), these numbers were not significantly
      different (25 patients, 86%). The mean number of postoperative infectious
      episodes per patient was also not significantly different: 1.77 (SDD) vs. 1.93
      (placebo). Infections involving Gram-negative aerobic bacteria and Candida
      species were significantly less frequent in patients receiving SDD (p <.001 and p
      <.05). Total costs were higher in the group receiving SDD. CONCLUSIONS: Selective
      decontamination of the digestive tract does not prevent infection in patients
      undergoing elective liver transplantation and increases the cost of their care.
      It does, however, affect the type of infection. Infections with Gram-negative
      bacilli and with Candida species are replaced by infections with Gram-positive
      cocci.

PMID- 12072670
TI  - Use of a peripheral perfusion index derived from the pulse oximetry signal as a
      noninvasive indicator of perfusion.
AB  - OBJECTIVE: Peripheral perfusion in critically ill patients frequently is assessed
      by use of clinical signs. Recently, the pulse oximetry signal has been suggested
      to reflect changes in peripheral perfusion. A peripheral perfusion index based on
      analysis of the pulse oximetry signal has been implemented in monitoring systems
      as an index of peripheral perfusion. No data on the variation of this index in
      the normal population are available, and clinical application of this variable in
      critically ill patients has not been reported. We therefore studied the variation
      of the peripheral perfusion index in healthy adults and related it to the central
      to-toe temperature difference and capillary refill time in critically ill
      patients after changes in clinical signs of peripheral perfusion. DESIGN:
      Prospective study. SETTING: University-affiliated teaching hospital. PATIENTS:
      One hundred eight healthy adult volunteers and 37 adult critically ill patients.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Capillary refill time,
      peripheral perfusion index, and arterial oxygen saturation were measured in
      healthy adults (group 1). Capillary refill time, peripheral perfusion index,
      arterial oxygen saturation, central-to-toe temperature difference, and
      hemodynamic variables were measured in critically ill patients (group 2) during
      different peripheral perfusion profiles. Poor peripheral perfusion was defined as
      a capillary refill time >2 secs and central-to-toe temperature difference > or =
      7 degrees C. Peripheral perfusion index and arterial oxygen saturation were
      measured by using the Philips Medical Systems Viridia/56S monitor. In group 1,
      measurements were made before and after a meal. In group 2, two measurements were
      made, with the second measurement taken when the peripheral perfusion profile had
      changed. A total of 216 measurements were carried out in group 1. The
      distribution of the peripheral perfusion index was skewed and values ranged from
      0.3 to 10.0, median 1.4 (inner quartile range, 0.7-3.0). Seventy-four
      measurements were carried out in group 2. A significant correlation between the
      peripheral perfusion index and the core-to-toe temperature difference was found
      (R2=.52; p <.001). A cutoff peripheral perfusion index value of 1.4 (calculated
      by constructing a receiver operating characteristic curve) best reflected the
      presence of poor peripheral perfusion in critically ill patients. Changes in
      peripheral perfusion index and changes in core-to-toe temperature difference
      correlated significantly (R =.52, p <.001). CONCLUSIONS: The peripheral perfusion
      index distribution in the normal population is highly skewed. Changes in the
      peripheral perfusion index reflect changes in the core-to-toe temperature
      difference. Therefore, peripheral perfusion index measurements can be used to
      monitor peripheral perfusion in critically ill patients.

PMID- 12072671
TI  - The hemodynamically unstable patient in the intensive care unit: hemodynamic vs.
      transesophageal echocardiographic monitoring.
AB  - OBJECTIVE: Transesophageal echocardiography is a diagnostic and monitoring
      modality. The objectives of our study were to compare the diagnoses obtained with
      continuous transesophageal echocardiography and hemodynamic monitoring in the
      intensive care unit, to determine interobserver variability of diagnosis obtained
      with both modalities, and to evaluate its impact. DESIGN: Prospective cohort
      study. SETTING: Surgical intensive care unit. PATIENTS: Consecutive
      hemodynamically unstable patients after cardiac surgery. INTERVENTIONS: At
      admission, unstable patients were monitored during 4 hrs with transesophageal
      echocardiography and standard hemodynamic monitoring. The critical care physician
      evaluated the patients based on all information except the transesophageal
      echocardiography at 0, 2, and 4 hrs and formulated a hypothesis on the most
      likely cause of hemodynamic instability. Transesophageal echocardiography
      information was provided after each evaluation. To evaluate interobserver
      variability, all the hemodynamic and echocardiographic information was gathered,
      randomized, and evaluated by five clinicians for the hemodynamic data and five
      echocardiographers for the transesophageal echocardiography data. The evaluators
      were blinded to all other information. Kappa statistics were used to evaluate
      agreement. Impact of transesophageal echocardiography was assessed
      retrospectively by using the Deutsch scale. RESULTS: Twenty patients qualified
      for the study. The agreement between the hemodynamic and echocardiographic
      diagnosis showed a kappa at admission, 2 hrs, and 4 hrs of 0.33, 0.47, and 0.28.
      The interobserver agreement for the initial diagnosis (p =.014) and between all
      evaluators (p <.001) was significantly higher in the echocardiographic compared
      with the hemodynamic group. The transesophageal echocardiographic information was
      considered retrospectively to be essential in 34% and valuable in 34% of cases.
      CONCLUSIONS: These observations support the belief that transesophageal
      echocardiographic monitoring in the intensive care unit is associated with higher
      interobserver agreement in diagnosing and excluding significant causes of
      hemodynamic instability for postoperative cardiac surgical patients.

PMID- 12072672
TI  - Effects of a multifaceted, multidisciplinary, hospital-wide quality improvement
      program on weaning from mechanical ventilation.
AB  - OBJECTIVE: To examine the effects of a mechanical ventilation weaning management
      protocol that was implemented as a hospital-wide, quality improvement program on
      clinical and economic outcomes. DESIGN: Prospective, before-and-after
      intervention study. Data from a preimplementation year are compared with those of
      the first 2 yrs after protocol implementation. PATIENTS AND SETTING: Patients
      older than 18 yrs in diagnosis-related group 475 and group 483, who were admitted
      to the adult medical, surgical, and cardiac intensive care units (ICU) in a
      university hospital. INTERVENTIONS: After the baseline year, a weaning management
      program was implemented throughout our institution. Primary endpoints were
      mortality, days on mechanical ventilation, ICU and hospital lengths of stay,
      hospital costs, and the percentage of patients requiring tracheostomy. MAIN
      RESULTS: The number of patients increased from 220 in the baseline year (year 0)
      to 247 in the first year (year 1), then to 267 in the second year (year 2). The
      mean Acute Physiology and Chronic Health Evaluation (APACHE) II score increased
      from 22.2 to 24.4 in year 1 (p =.006) and to 26.2 in year 2 (p <.0005). When year
      0 was compared with year 1, mean days on mechanical ventilation decreased from
      23.9 to 21.9 days (p =.608), hospital length of stay decreased from 37.5 to 31.6
      days (p =.058), ICU length of stay decreased from 30.5 to 25.9 days (p =.133),
      and total cost per case decreased from $92,933 to $78,624 (p =.061). When year 0
      was compared with year 2, mean days on mechanical ventilation decreased from 23.9
      days to 17.5 days (p =.004), mean hospital length of stay decreased from 37.5 to
      24.7 days, mean ICU length of stay decreased from 30.5 to 20.3 days, total cost
      per case decreased from $92,933 to $63,687, and percentage of patients requiring
      tracheotomy decreased from 61% to 41% (all p <.0005). There was also a reduction
      in the percentage of patients requiring more than one course of mechanical
      ventilation during the hospitalization from 33% to 26% (p =.039), a total cost
      savings of $3,440,787 and a decrease in mortality between all 3 yrs from 32% to
      28% (p =.062). CONCLUSIONS: A multifaceted, multidisciplinary weaning management
      program can change the process of care used for weaning patients from mechanical
      ventilation throughout an acute care hospital and across multiple services. This
      change can lead to large reductions in the duration of mechanical ventilation,
      length of stay, and hospital costs, even at a time when patients are sicker.

PMID- 12072673
TI  - Is propofol safe for procedural sedation in children? A prospective evaluation of
      propofol versus ketamine in pediatric critical care.
AB  - OBJECTIVES: To compare propofol with ketamine sedation delivered by pediatric
      intensivists during painful procedures in the pediatric critical care department
      (PCCD). DESIGN: Prospective 15-month study. SETTING: An 18-bed multidisciplinary,
      university-affiliated PCCD. INTERVENTIONS: All children were randomized to the
      propofol or ketamine protocol according to prescheduled procedure dates. Propofol
      was delivered by continuous infusion after a loading bolus dose and a minidose of
      lidocaine (PL). Ketamine was given as a bolus injection together with midazolam
      and fentanyl (KMF). Repeated bolus doses of both drugs were given to achieve the
      desired level of anesthesia. The studied variables included procedures performed,
      anesthetic drug doses, procedure and recovery durations, and side effect
      occurrence. The patient's parents, PCCD nurse and resident physician, pediatric
      intensivist, and the physician performing the procedure graded the adequacy of
      anesthesia. MEASUREMENTS AND MAIN RESULTS: Of the 105 procedures in 98 children,
      PL sedation was used in 58 procedures, and KMF was used in 47. Recovery time was
      23 mins for PL and 50 mins for KMF, and total PCCD monitoring was 43 mins for PL
      and 70 mins for KMF. Five children (10.6%) in the KMF group and in none in the PL
      group experienced discomfort during emergence from sedation. Transient decreases
      in blood pressure, partial airway obstruction, and apnea were more frequent in
      the PL than in the KMF sedation. All procedures were successfully completed, and
      no child recalled undergoing the procedure. The overall sedation adequacy score
      was 97% for PL and 92% for KMF (p <.05). CONCLUSIONS: Both PL and KMF anesthesia
      are effective in optimizing comfort in children undergoing painful procedures. PL
      scored better by all evaluators, recovery from PL anesthesia after procedural
      sedation was more rapid, total PCCD stay was shorter with PL, and emergence from
      PL was smoother than with KMF. Because transient respiratory depression and
      hypotension are associated with PL, it is considered safe only in a monitored
      environment (e.g., a PCCD).

PMID- 12072674
TI  - Erythromycin and early enteral nutrition in mechanically ventilated patients.
AB  - OBJECTIVE: To determine whether erythromycin facilitates early enteral nutrition
      in mechanically ventilated, critically ill patients. DESIGN: Prospective,
      randomized, placebo-controlled, single-blind trial. SETTING: General intensive
      care unit in a university-affiliated general hospital. PATIENTS: Forty
      consecutive critically ill patients receiving invasive mechanical ventilation and
      early nasogastric feeding. INTERVENTIONS: Patients were assigned randomly to
      intravenous erythromycin (250 mg/6 hrs; n = 20) or a placebo (intravenous 5%
      dextrose, 50 mL/6 hrs; n = 20) for 5 days. The first erythromycin or 5% dextrose
      injection was given at 8 am on the day after intubation. One hour later, a daily
      18-hr enteral nutrition regimen via a 14-Fr gastric tube was started. Residual
      gastric volume was aspirated and measured every day at 9 am, 3 pm, 9 pm, and 3
      am. Enteral nutrition was discontinued if residual gastric volume exceeded 250 mL
      or the patient vomited. MEASUREMENTS AND MAIN RESULTS: On the first day, residual
      gastric volume was smaller in the erythromycin than in the placebo group (3 pm,
      15 +/- 7 mL vs. 52 +/- 14 mL, p <.05; 9 pm, 29 +/- 15 mL vs. 100 +/- 20 mL, p
      <.001; 3 am, 11 +/- 4 mL vs. 54 +/- 13 mL, p <.05). With erythromycin, residual
      gastric volume at 9 pm was smaller on the second day (33 +/- 11 mL vs. 83 +/- 19
      mL, p <.01) and residual gastric volume at 3 pm was smaller on the third day (39
      +/- 15 mL vs. 88 +/- 19 mL, p <.05) than with placebo. On the fourth and fifth
      days, the differences in residual gastric volume were not significant. Enteral
      nutrition was discontinued before the end of the 5-day period in seven of the 20
      erythromycin patients and 14 of the 20 placebo patients (p <.001). CONCLUSION: In
      critically ill patients receiving invasive mechanical ventilation, erythromycin
      promotes gastric emptying and improves the chances of successful early enteral
      nutrition.

PMID- 12072675
TI  - Aminoglycoside and glycopeptide renal toxicity in intensive care patients studied
      by proton magnetic resonance spectroscopy of urine.
AB  - OBJECTIVE: Aminoglycoside and glycopeptide antibiotics are responsible for renal
      toxicity. In most cases, the nephrotoxicity is limited to a reversible tubular
      injury, but an acute and sustained renal failure may occur. The aim of our study
      was to explore the renal function of patients given these antimicrobial agents
      with proton magnetic resonance spectroscopy of urine. This technique is able to
      detect, in urine samples, a wide range of metabolites reflecting renal tubular
      function. The variables assessed by magnetic resonance spectroscopy were compared
      with the routine markers of renal function: creatinine, urea, and 24-hr urine
      volume. DESIGN: Prospective clinical study. SETTING: Intensive care unit.
      PATIENTS: All patients in an intensive care unit receiving an aminoglycoside
      and/or a glycopeptide were included in the study if they presented with signs of
      renal dysfunction. All experiments were performed on urine samples collected for
      the routine follow-up of these patients. INTERVENTION: Proton spectra were
      acquired with water suppression, and the peak intensity of each metabolite was
      reported in relationship to the intensity of the creatinine peak. MEASUREMENTS
      AND MAIN RESULTS: The ratio values obtained by magnetic resonance spectroscopy
      were compared with the values of creatininemia and blood urea obtained routinely
      by biochemistry and with the value of the 24-hr urine volume by logistic
      regression and general linear models. This statistical analysis showed that the
      ratio of dimethylamine to creatinine was highly correlated with creatininemia.
      CONCLUSIONS: Dimethylamine is an osmolyte released from the medullar region of
      the kidney. Thus, our study demonstrated that nephrotoxicity from aminoglycosides
      and glycopeptides is not limited to proximal tubular toxicity but also may
      involve the medullar region (Henle loop and collecting duct) of the nephron.

PMID- 12072676
TI  - Inspired superoxide anions attenuate blood lactate concentrations in
      postoperative patients.
AB  - OBJECTIVE: Low concentrations of superoxide (O(2)(-)) constitute a portion of
      atmosphere negative ions in the form of O(2)-(H(2)O)(n), which has been reported
      to have a stimulatory effect on superoxide dismutase activity. If superoxide
      dismutase is activated by inspired negative ions containing O(2)(-), aerobic
      metabolism could be improved. To test this hypothesis, we examined blood lactate
      concentrations in postoperative patients with or without inhalation of air from a
      home humidifier that generates O(2)-(H(2)O)(n). DESIGN: Prospective, randomized,
      controlled trial. SETTING: Neurosurgical intensive care unit of a general
      hospital. PATIENTS: Twenty postneurosurgical patients with arterial blood lactate
      concentrations >1.5 mmol/L were studied and were divided randomly into two
      groups. INTERVENTIONS: One group received 40 L/min 40% oxygen flow from a home
      humidifier as an oxygen therapy for 4 hrs, followed by almost the same flow from
      a jet nebulizer, which generates positive ions, for 4 hrs. The other group
      received the reverse combination. MEASUREMENTS AND MAIN RESULTS: During the 8-hr
      study, arterial blood lactate concentrations were measured every hour. There was
      a significant difference in the time course of blood lactate concentrations
      between the groups. In the group in which negative ions were first initiated for
      4 hrs and positive ions thereafter, the lactate concentration decreased slightly
      at 3, 4, and 5 hrs and returned to the baseline concentration thereafter. In the
      group with the reverse combination, the lactate concentration did not change
      during the first 4 hrs but decreased thereafter after inhalation of negative
      ions. CONCLUSIONS: Inspired O(2)(-) attenuates blood lactate concentrations. This
      may be attributed, in part, to the systemic stimulatory effect on superoxide
      dismutase activity, which accelerates oxidative phosphorylation in the
      mitochondria, thus attenuating lactate generation.

PMID- 12072677
TI  - A pilot study of coupled plasma filtration with adsorption in septic shock.
AB  - OBJECTIVE: To test the hypothesis that nonselective plasma adsorption by a
      hydrophobic resin (coupled plasmafiltration and adsorption) could improve
      hemodynamics and restore leukocyte responsiveness in patients with septic shock.
      DESIGN: Prospective, pilot, crossover clinical trial. SETTING: General intensive
      care unit in a teaching hospital. SUBJECTS: Ten patients with hyperdynamic septic
      shock. INTERVENTIONS: Patients were randomly allocated to 10 hrs of either
      coupled plasma filtration adsorption plus hemodialysis (treatment A) or
      continuous venovenous hemodiafiltration (treatment B) in random order. We
      measured the change in mean arterial pressure, norepinephrine requirements, and
      leukocyte tumor necrosis factor-alpha (TNF-alpha) production (both spontaneous
      and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested
      TNF-alpha production from normal human adherent monocytes incubated with
      patients' plasma obtained before and after the resin, both with or without
      incubation with an anti-interleukin-10 monoclonal antibody. RESULTS: Mean
      arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5
      mm Hg with treatment B (p =.001). There was an average decrease of norepinephrine
      requirement of 0.08 microg/kg/min with treatment A and 0.0049 microg/kg/min with
      treatment B (p =.003). All patients but one survived. Spontaneous and
      lipopolysaccharide-induced TNF-alpha production from patients' whole blood
      increased over time with treatment A. This increase was more marked in blood
      drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p =.009).
      Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-alpha
      by 1 x 10(6)cultured adherent monocytes from healthy donors. This suppressive
      effect was significantly reduced after passage of plasma through the resin (p
      =.019) and after incubation with anti-interleukin-10 monoclonal antibodies (p
      =.028). CONCLUSIONS: In patients with septic shock, coupled plasmafiltration
      adsorption combined with hemodialysis was associated with improved hemodynamics
      compared with continuous venovenous hemodiafiltration. This result might be
      related to its ability to restore leukocyte responsiveness to lipopolysaccharide.
      These findings suggest a potential role for blood purification in the treatment
      of septic shock.

PMID- 12072679
TI  - Catheter replacement in continuous arteriovenous hemodiafiltration: the balance
      between infectious and mechanical complications.
AB  - OBJECTIVE: To assess the optimal moment of central vascular catheter replacement
      balancing infectious and mechanical complications in continuous renal replacement
      therapies in critically ill patients with acute renal failure. METHODS:
      Prospective sequential trial with historical controls to compare liberal catheter
      replacement when clinically indicated with routine catheter replacement every 5
      days in consecutive patients treated by continuous arteriovenous
      hemodiafiltration in a level I secondary referral intensive care unit of a
      university-affiliated teaching hospital. Intention-to-treat analysis.
      MEASUREMENTS AND MAIN RESULTS: Twenty-two patients underwent catheter replacement
      when clinically indicated (group II), and 21 patients served as historical
      controls (group I). The groups were comparable for sex, age, Acute Physiology and
      Chronic Health Evaluation II scores, comorbidity, and creatinin and urea levels
      at the start of continuous arteriovenous hemodiafiltration. In group I, 71
      catheters were used for 346 treatment days, and in group II, 68 catheters were
      used for 495 treatment days. The mean duration of catheterization was 4.9 +/- 2.0
      days vs. 7.3 +/- 4.5 days, respectively (Student's t-test p <.001). There was no
      significant difference between the incidence of colonization of catheters (46.8%
      in group I vs. 39.1% in group II; chi-square p =.35) In group I, bacteremia and
      catheter sepsis occurred in two patients, whereas this did not occur in group II.
      The occurrence of mechanical complications was comparable in both groups (15.5%
      in group I vs. 19.1% in group II). There were significantly more mechanical
      complications with arterial vs. venous catheters (17 vs. 7; chi-square p =.027).
      CONCLUSION: When catheters were changed as clinically indicated, they remained
      significantly longer in situ vs. being replaced routinely every 5 days;
      infectious and mechanical complications were comparable. The incidence of
      catheter sepsis was low (2.2%), and no prosthesis infection occurred. Catheter
      replacement when clinically indicated seems to be as safe as routine replacement
      every 5 days.

PMID- 12072678
TI  - A dose-ranging study of midazolam for postoperative sedation of patients: a
      randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To evaluate the dose range, efficacy, and safety of midazolam for
      induction of sedation of mechanically ventilated postoperative patients in the
      intensive care unit. DESIGN: A randomized, double-blind, placebo-controlled
      study. SETTING: Thirteen intensive care units in Japan. PATIENTS: We included 98
      patients undergoing general surgery who were ASA physical status I-III. The
      following inclusion criteria were applied to the patients after surgery: under
      mechanical ventilation, sedation level 2 or 3 on the Ramsay Sedation Scale, and
      any pain level but 4 on the Pybus and Torda Pain Scale. MEASUREMENTS AND RESULTS:
      Of the 98 patients initially enrolled in the study, 95 patients received one of
      the study medications: placebo (n = 24), 0.015 mg/kg midazolam (n = 21), 0.03
      mg/kg midazolam (n = 26), or 0.06 mg/kg midazolam (n = 24). Level of sedation was
      assessed by using the Ramsay Sedation Scale before and 10 mins after medication.
      The proportions of patients with sedation level 4 or deeper after medication were
      4.3%, 14.3%, 52.0%, and 90.9% in the placebo and the midazolam 0.015 mg/kg, 0.03
      mg/kg, and 0.06 mg/kg groups, respectively. Safety was assessed by routine
      monitoring of body functions and monitoring for adverse events. Although
      midazolam dose-dependently reduced mean systolic arterial pressure, the changes
      in this variable were small; only one or two patients in each treatment group had
      decreases in systolic arterial pressure of >20%. No clear dose dependency was
      found for changes in other body functions measured in the intensive care unit.
      CONCLUSION: The proportion of patients who achieved a satisfactory level of
      sedation increased with an increasing dose of midazolam. Intravenous bolus
      injection of midazolam also dose-dependently reduced mean systolic arterial
      pressure. This study indicated that, balancing sedative efficacy and safety, from
      0.03 to 0.06 mg/kg of midazolam provides relatively safe sedation in
      postoperative patients.

PMID- 12072680
TI  - Adrenal insufficiency in critically ill patients with human immunodeficiency
      virus.
AB  - OBJECTIVE: The adrenal gland is the endocrine organ most commonly involved in
      patients infected with human immunodeficiency virus (HIV). It is important to
      recognize patients with adrenal insufficiency, because this disorder may be fatal
      if untreated. The incidence of adrenal insufficiency in critically ill HIV
      infected patients is unclear, partly because different criteria are used to
      diagnose adrenal insufficiency. To help clarify the incidence of adrenal
      insufficiency in HIV-infected critically ill patients, we compared the incidence
      based on the stress cortisol concentration, low-dose corticotropin stimulation
      test, and high-dose corticotropin stimulation test. SETTING: Medical intensive
      care unit. PATIENTS: Twenty-eight critically ill patients with HIV, mean age 43
      +/- 9 years; 20 were male; 54% died. INTERVENTIONS: We performed a 1-microg (low
      dose adrenocorticotropic hormone; LD-ACTH) and 249 microg (high-dose; HD-ACTH)
      corticotropin stimulation test in HIV-infected critically ill patients not
      receiving corticosteroids. According to results of the stress serum cortisol
      concentration and LD-ACTH and HD-ACTH tests, patients were classified as having
      adrenal insufficiency or as normal. The results of newly revised diagnostic
      criteria for adrenal insufficiency (i.e., stress cortisol concentration and
      cortisol response to LD-ACTH <25 microg/dL) were compared with the traditional
      criteria (i.e., stress cortisol level and response to HD-ACTH <18 microg/dL). In
      addition, the associations between adrenal insufficiency and the CD4 count, human
      cytomegalovirus antigenemia, and other risk factors for adrenal insufficiency
      were determined. MEASUREMENTS AND MAIN RESULTS: When we used a stress cortisol
      concentration <18 microg/dL as the sole diagnostic threshold for diagnosis of
      adrenal insufficiency, 50% (14 of 28) of patients had adrenal insufficiency. The
      incidence was 75% (21 of 28) when we used a diagnostic threshold of <25 microg/dL
      for the stress cortisol concentration. When we used both the stress cortisol
      concentration and LD-ACTH test with a diagnostic cortisol threshold concentration
      <18 microg/dL, 21% (six of 28) had adrenal insufficiency. The incidence was 46%
      (13 of 28) when we used a cortisol diagnostic threshold concentration of <25
      microg/dL. When we used both the stress cortisol concentration and the HD-ACTH
      stimulation test with a diagnostic cortisol threshold of <18 microg/dL, 7% (two
      of 28) had adrenal insufficiency. The incidence of adrenal insufficiency was 21%
      (six of 28) with a cortisol diagnostic threshold value of <25 microg/dL. Human
      cytomegalovirus antigenemia was the only variable assessed that was associated
      with adrenal insufficiency. CONCLUSION: There is a high incidence of adrenal
      insufficiency in critically ill HIV-infected patients that varies with the
      criteria used to diagnose adrenal insufficiency. The LD-ACTH stimulation test is
      more sensitive than the high-dose test for diagnosing adrenal insufficiency in
      this population. Because of the high incidence of inadequate adrenal function,
      all critically ill HIV-infected patients should undergo an evaluation for adrenal
      insufficiency with the stress cortisol concentration and LD-ACTH stimulation
      tests.

PMID- 12072681
TI  - Multiple organ dysfunction associated with severe acute pancreatitis.
AB  - OBJECTIVE: To compare three different multiple organ dysfunction scores in
      predicting hospital mortality rates and to discover which one best assesses organ
      dysfunction/failure in patients with severe acute pancreatitis in a general
      intensive care unit. DESIGN: Retrospective, observational study. SETTING:
      Surgical department and a ten-bed general intensive care unit in a tertiary care
      hospital. PATIENTS: Among the 178 consecutive patients admitted to the surgical
      department with severe acute pancreatitis from 1994 to 1998, 113 patients treated
      in the general intensive care unit underwent study. INTERVENTIONS: None.
      MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data were collected during
      a period of 35 days. Acute Physiology and Chronic Health Evaluation (APACHE) II,
      Multiple Organ Dysfunction (MOD) score, Sequential Organ Failure Assessment
      (SOFA) score, and Logistic Organ Dysfunction (LOD) score were calculated and
      compared regarding hospital mortality rate. In addition, daily maximum score and
      a total maximum score (sum of the highest values for each organ dysfunction) were
      calculated for all three scores. The area under the receiver operating
      characteristic curve was used as a measure of accuracy of the scores. The highest
      accuracy was revealed with daily maximum scores with the area under the receiver
      operating characteristic curve 0.847 for SOFA, 0.844 for MOD, and 0.836 for LOD.
      According to the maximum SOFA score, the highest mortality rate was associated
      with liver (83%, p <.001) and renal (63%, p <.001) failures. The mortality ratio
      with two organ failures ranged from 50% to 91%. The highest mortality rate (91%)
      was for a combination of hepatic and renal failure. In multiple logistic
      regression analysis, only hepatic, renal, and cardiovascular failure and previous
      cardiovascular medication were independent risk factors for hospital mortality.
      CONCLUSION: In patients with severe acute pancreatitis, organ dysfunction scores
      (MOD, SOFA, LOD) show good accuracy, comparable with APACHE II in predicting
      hospital mortality. The maximum daily organ dysfunction scores were simple and
      useful in assessing multiple organ dysfunction and in predicting hospital
      mortality rates of patients with severe acute pancreatitis.

PMID- 12072682
TI  - Reversible myocardial dysfunction in critically ill, noncardiac patients: a
      review.
AB  - OBJECTIVE: To review reversible myocardial dysfunction affecting critically ill
      patients without cardiac pathology. DATA SOURCES: The bibliography for the study
      was compiled through a search of different databases for the period 1966-2001.
      References cited in the selected articles also were reviewed. STUDY SELECTION:
      The selection criteria included all articles published on reversible myocardial
      dysfunction in critically ill patients. CONCLUSIONS: Reversible myocardial
      dysfunction may develop in a situation of critical pathology, but the etiology of
      reversible myocardial dysfunction is not fully understood. This dysfunction may
      be accompanied by increases in enzyme concentrations and electrocardiographic
      changes. Reversible myocardial dysfunction probably is underdiagnosed, although
      its presence is associated with a worsening of the prognosis and with more
      specific therapeutic options. Further studies are necessary to define its true
      incidence and clinical implications.

PMID- 12072683
TI  - Time course of nitric oxide, peroxynitrite, and antioxidants in the endotoxemic
      heart.
AB  - OBJECTIVES: To determine the time course for myocardial production of nitric
      oxide, peroxynitrite, and glutathione, to determine the activities of the
      myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and
      glutathione reductase throughout endotoxemia and into recovery, and to correlate
      the levels of these variables to left ventricular contractility in endotoxemia.
      DESIGN: Rats were treated with lipopolysaccharide. Endotoxemic hearts were
      examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time
      control groups were treated identically. SETTING: A pulmonary research laboratory
      of a university teaching hospital. MEASUREMENTS AND MAIN RESULTS:
      Lipopolysaccharide administration resulted in decreased contractility at 16 hrs
      as assessed by the isolated papillary muscle technique. Contractility recovered
      by 24 hrs. Myocardial glutathione content initially increased, but it was
      decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both
      superoxide dismutase and glutathione reductase activities were increased early (4
      hrs) and remained elevated throughout the course of the experiment. Myocardial
      nitric oxide content (assessed by the chemiluminescence technique) was increased
      by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained
      elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite
      (assessed by measurement of 3-nitrotyrosine by high-pressure liquid
      chromatography) was elevated at 16 hrs and remained elevated despite
      normalization of contractility at 24 and 48 hrs. CONCLUSIONS: Myocardial
      dysfunction in endotoxemia correlates mainly with decreased glutathione content
      and glutathione peroxidase activity rather than nitric oxide or peroxynitrite
      formation. These data indicate that lipopolysaccharide-induced myocardial
      dysfunction is not solely caused by elevated myocardial nitric oxide levels but
      rather caused by the sum of complex interactions between various oxygen- and
      nitrogen-derived radicals.

PMID- 12072684
TI  - Restoration of renal function in shock by perfusion of the renal artery with
      venous blood: a counterintuitive approach.
AB  - OBJECTIVE: Acute renal failure (ARF) in low-flow states may be reversed by
      increasing renal perfusion. When hemodynamics are maximized, renal perfusion can
      only be improved by shunting a higher proportion of cardiac output to the kidney;
      however, in low-flow states, this reduces already compromised systemic pressure
      and perfusion to other organs. Increasing perfusion using venous blood (VB) would
      be an attractive option because decreased systemic pressure and perfusion to
      other organs could be avoided. However, it is not known whether VB can provide
      adequate oxygen delivery to restore or maintain renal function. We studied
      whether antegrade VB perfusion of the kidney via the renal artery would restore
      urine output (UO) and glomerular filtration rate (GFR) in hypoperfused ARF.
      DESIGN: Shock was induced in six dogs via a hemorrhagic protocol resulting in a
      systolic blood pressure of 50-70 mm Hg, a mixed venous oxygen saturation of 25%
      to 40%, and a UO <10% of baseline. After 60 mins of shock, the left renal artery
      was cannulated under fluoroscopy and perfused at pressures of 100-150 mm Hg for
      30 mins with VB drawn from the vena cava and delivered by an extracorporeal pump
      system. The right kidneys were controls and remained hypoperfused. RESULTS: All
      VB-perfused kidneys recovered renal function after a sustained period of shock
      and marked oliguria: UO from 0.7 +/- 1.6 mL/hr to 101 +/- 58 mL/hr (p <.01); GFR
      from approximately 0 to 70.3 +/- 55 mL/min (p =.04). The control kidneys' UO (0.7
      +/- 1.6 mL/hr) and GFR (0 mL/min) remained unchanged throughout the study. The
      experimental kidneys were able to extract oxygen from VB (O2 saturation, 31 +/-
      7% to 16 +/- 4%; p =.01). CONCLUSION: When flow is controlled, kidneys in
      hypoperfused ARF can extract sufficient oxygen from antegrade VB perfusion to
      restore renal function (UO and GFR).

PMID- 12072685
TI  - Continuous on-line measurement of absolute left ventricular volume by
      transcardiac conductance: angiographic validation in sheep.
AB  - OBJECTIVE: Validation of the transcardiac conductance method for continuous, on
      line measurement of absolute left ventricular volume by comparison with biplane
      angiography. DESIGN: Controlled, prospective animal study. SETTING:
      Catheterization laboratory of the Leiden University Medical Center. SUBJECTS: Six
      anesthetized sheep. INTERVENTIONS: Subjects were studied at baseline, during
      infusion of dobutamine, and during volume loading and beta blockade. In a pilot
      experiment, a coronary artery was occluded by a balloon, and the behavior of the
      transcardiac conductance signals during ischemia was tested. MEASUREMENTS AND
      MAIN RESULTS: Calibration factors alpha and V(p) were determined by
      thermodilution and hypertonic saline dilution, respectively. Calibrated
      transcardiac conductance volume was compared with angiographic volume in four
      different hemodynamic conditions, and transcardiac conductance measurements were
      registered during a period of ischemia. Results showed a good linear correlation
      between transcardiac conductance and angiographic volume (r =.77, p <.01) with an
      intercept of 12.5 +/- 5.6 mL (interanimal variability, 17.8 mL) and a slope of
      1.49 +/- 0.15 (interanimal variability, 0.34). Mean alpha and V(p) were 0.12 +/-
      0.01 (interanimal variability, 0.07) and 104 +/- 3 mL (interanimal variability,
      38 mL), respectively. V(p) did not vary significantly between conditions, and
      alpha varied only during propranolol (p =.04). Transcardiac conductance enabled
      immediate visualization of acute left ventricular volume changes during coronary
      occlusion in a pilot experiment. CONCLUSIONS: Transcardiac conductance is a
      method to register an on-line, continuous, left ventricular volume signal, which
      correlates well with angiography. However, calibration factors need to be
      determined in individual subjects. The method appears promising to monitor
      absolute volume in the intensive care unit.

PMID- 12072686
TI  - Inducible nitric oxide synthase pathway in the central nervous system and
      vasopressin release during experimental septic shock.
AB  - BACKGROUND: Septic shock is characterized by arteriolar vasodilation and
      hypotension. We have tested the hypothesis that nitric oxide arising from
      inducible nitric oxide synthase in the central nervous system is responsible for
      the deficiency in vasopressin release and consequent hypotension during
      experimental septic shock. METHODS AND RESULTS: Septic shock was induced in male
      Wistar rats by intravenous injection of 1.5 mg/kg lipopolysaccharide. After
      lipopolysaccharide administration, we found a significant decrease in mean
      arterial pressure with a concomitant increase in heart rate, a significant
      decrease in diuresis, and a transitory decrease in body temperature. An increase
      in plasma vasopressin concentrations occurred in these animals and was present
      for 2 hrs after lipopolysaccharide administration, returning close to basal
      concentrations thereafter and remaining unchanged for the next 24 hrs. When
      lipopolysaccharide was combined with central administration of aminoguanidine, an
      inducible nitric oxide synthase inhibitor, we observed a sustained increase in
      plasma vasopressin concentration and in the maintenance of blood pressure at 4
      and 6 hrs after lipopolysaccharide treatment compared with rats treated with
      lipopolysaccharide alone. CONCLUSION: These data indicate that central nitric
      oxide arising from the inducible nitric oxide synthase pathway plays an important
      inhibitory role in vasopressin release during experimental septic shock and may
      be responsible for the hypotension occurring in this vasodilatory shock.

PMID- 12072687
TI  - Vasopressin improves survival in a pig model of hypothermic cardiopulmonary
      resuscitation.
AB  - OBJECTIVE: During hypothermic cardiopulmonary resuscitation with a body core
      temperature <30 degrees C administration of a vasopressor to support coronary
      perfusion pressure is controversial. The purpose of the current study was to
      assess the effects of a single 0.4-unit/kg dose of vasopressin on coronary
      perfusion pressure, defibrillation success, and 1-hr survival in a pig model of
      hypothermic closed-chest cardiopulmonary resuscitation combined with rewarming.
      DESIGN: Prospective, randomized study in an established pig model. SETTING:
      University hospital research laboratory. SUBJECTS: Fifteen 12- to 16-wk-old
      domestic pigs. INTERVENTIONS: Pigs were surface cooled to a body core temperature
      of 26 degrees C and ventricular fibrillation was induced. After 15 mins of
      untreated cardiac arrest, manual closed-chest cardiopulmonary resuscitation and
      thoracic lavage with 40 degrees C warmed tap water were started. After 3 mins of
      external chest compression, animals were assigned randomly to receive vasopressin
      (0.4 units/kg, n = 8; or saline placebo, n = 7). Defibrillation was attempted 10
      mins after drug administration. MEASUREMENTS AND MAIN RESULTS: Compared with
      saline placebo treated-animals, coronary perfusion pressure in vasopressin
      treated pigs was significantly higher 90 secs (36 +/- 5 mm Hg vs. 7 +/- 4 mm Hg,
      p =.000) to 10 mins (24 +/- 4 mm Hg vs. 8 +/- 4 mm Hg, p =.000) after drug
      administration. Restoration of spontaneous circulation and 1 hr survival were
      significantly higher in vasopressin animals compared with saline placebo (8 of 8
      vasopressin pigs vs. 0 of 7 placebo pigs, p <.001). CONCLUSIONS: A single 0.4
      unit/kg dose of vasopressin administered at a body core temperature <30 degrees C
      significantly improved defibrillation success and 1-hr survival in a pig model of
      hypothermic cardiopulmonary resuscitation.

PMID- 12072688
TI  - Alveolar mechanics alter hypoxic pulmonary vasoconstriction.
AB  - OBJECTIVES: Hypoxic pulmonary vasoconstriction is the primary physiologic
      mechanism that maintains a proper ventilation/perfusion match, but it fails in
      diffuse lung injuries such as acute respiratory distress syndrome. Acute
      respiratory distress syndrome is associated with pulmonary surfactant loss that
      alters alveolar mechanics (i.e., dynamic change in alveolar size and shape during
      ventilation), converting normal stable alveoli into unstable alveoli. We
      hypothesized that alveolar instability stents open pulmonary microvessels and is
      the mechanism of hypoxic pulmonary vasoconstriction failure associated with acute
      respiratory distress syndrome. DESIGN: Prospective, randomized, controlled study.
      SETTING: University research laboratory. SUBJECTS: Ten adult pigs. INTERVENTIONS:
      Anesthetized ventilated pigs were prepared surgically for hemodynamic monitoring
      and were subjected to a right thoracotomy. An in vivo microscope was attached to
      the right lung, and the microvascular response to hypoxia (F(IO(2)), 15%) was
      measured in a lung with normal stable alveoli and in a lung with unstable alveoli
      caused by surfactant deactivation (Tween lavage). MEASUREMENTS AND MAIN RESULTS:
      Alveolar instability, defined as the difference between alveolar area at peak
      inspiration and end expiration and assessed as a percentage change (I-E Delta%),
      was significantly increased after Tween (23.9 +/- 3.0, I-E Delta%) compared with
      baseline (2.4 +/- 1.0, I-E Delta%). Alveolar instability was associated with the
      following microvascular changes: a) increased vasoconstriction (Tween, 14.9 +/-
      1.0%) in response to hypoxia compared with baseline (10.8 +/- 1.2%, p <.05); and
      b) increased mean vascular diameter (Tween, 41.2 +/- 1.5 microm) compared with
      the mean diameter at baseline (24.6 +/- 1.0 microm, p <.05). CONCLUSION: Unstable
      alveoli stent open pulmonary vessels, which may explain the failure of hypoxic
      pulmonary vasoconstriction in acute respiratory distress syndrome.

PMID- 12072689
TI  - Systemic and pulmonary effector cell function after injury.
AB  - OBJECTIVE: Traumatic injury initiates a complex inflammatory response that is
      associated with end-organ dysfunction, immunosuppression, and the development of
      nosocomial infection. We hypothesize that the lungs of injured patients
      experience a unique inflammatory response to traumatic injury in which the
      ability of alveolar effector cells to respond to a bacterial challenge is
      impaired. DESIGN: Prospective, longitudinal comparative study. SETTING: The
      surgical intensive care unit of an ACS level I trauma center. PATIENTS: Forty
      consecutive multiple trauma patients requiring mechanical ventilation.
      MEASUREMENT: Blood and bronchoalveolar lavage fluid were collected on admission,
      24, and 48 hrs postinjury. Interleukin (IL)-6, IL-8, and IL-10 were measured in
      each sample initially and after lipopolysaccharide stimulation by using an ex
      vivo model of whole blood and bronchoalveolar lavage fluid cellular contents.
      Five patients who underwent elective surgery formed a control group. MAIN
      RESULTS: Systemic and alveolar levels of IL-6, IL-8, and IL-10 increase
      dramatically after severe injury. Levels of IL-6 and IL-8 in trauma
      bronchoalveolar lavage fluid are significantly greater than those of the systemic
      circulation. Whereas whole blood up-regulates production of IL-6 and IL-8 in
      response to lipopolysaccharide, bronchoalveolar lavage fluid cellular contents do
      not. In contrast, bronchoalveolar lavage fluid and whole blood from injured
      patients contain similar amounts of IL-10 and both up-regulate IL-10 production
      in response to lipopolysaccharide. CONCLUSION: The lungs of injured patients
      experience a profound proinflammatory response to injury more severe than that of
      the systemic circulation. Within this setting, the ability of alveolar effector
      cells to respond to a bacterial challenge is diminished compared with that of
      systemic cells. As such, alveolar effector cell function after injury seems to be
      impaired, possibly explaining the high frequency of pulmonary infection among
      these patients.

PMID- 12072690
TI  - Selective decontamination of the digestive tract: impact on cytokine release and
      mucosal damage after hemorrhagic shock.
AB  - OBJECTIVE: To determine if selective decontamination of the digestive tract (SDD)
      influences the proinflammatory immune response of the gut after hemorrhage.
      DESIGN: Random assignment to either unmanipulated control after 7 days of SDD or
      conventional rat chow, or hemorrhagic shock group after the same time of
      conventional rat chow or SDD. SETTING: University animal laboratory. SUBJECTS:
      Male Wistar rats, weighing between 300 and 350 g. INTERVENTION: Animals of the
      control group were not manipulated until organ harvesting, whereas animals of the
      hemorrhagic shock group were bled to 30 +/- 5 mm Hg for 90 mins by
      withdrawal/reinfusion of shed blood and were resuscitated by Ringer's lactate
      equivalent to the shed blood volume. MEASUREMENTS AND MAIN RESULTS: Rats were
      killed after resuscitation (hemorrhagic shock group) or completed feeding
      (control group). Whole portal and caval blood was obtained, and splenic
      macrophages and gut mononuclear cells were harvested to measure supernatant tumor
      necrosis factor-alpha and IL-6 by bioassay. Mesenteric lymph nodes were obtained
      to determine bacterial translocation, and a histologic specimen was taken from
      the distal ileum. Feces were harvested to examine the effect of SDD. SDD
      eliminated Gram-negative enteric bacteria and had no influence on mucosal damage
      or on bacterial translocation in control animals and animals after hemorrhage. In
      animals receiving conventional rat chow, hemorrhagic shock led to significantly
      (p <.05) elevated lipopolysaccharide-stimulated proinflammatory cytokine (tumor
      necrosis factor-alpha and interleukin-6) release in whole portal blood, splenic
      macrophages, and gut mononuclear cells compared with the control group without
      shock. In contrast, hemorrhagic shock after SDD led to suppressed or unchanged
      cytokine release compared with unmanipulated animals receiving SDD. However, SDD
      itself induced significant (p <.05) cytokine release in these organs.
      Furthermore, plasma concentrations of tumor necrosis factor-alpha and interleukin
      6 were significantly (p <.05) elevated in animals after hemorrhage and SDD
      compared with animals after hemorrhage alone. CONCLUSIONS: Hemorrhagic shock led
      to significant cytokine release. In contrast, cytokine release after hemorrhage
      and SDD was unchanged or suppressed. Furthermore, in control animals without
      hemorrhagic shock, SDD induced significant cytokine release. Therefore, selective
      decontamination of the gut, as practiced in some patients, may induce additional
      proinflammatory cytokine release, which can add to the proinflammatory burst in
      case of a complication such as hemorrhagic shock.

PMID- 12072691
TI  - Effect of increasing norepinephrine dosage on regional blood flow in a porcine
      model of endotoxin shock.
AB  - OBJECTIVE: To evaluate the effect of a norepinephrine-induced differential
      increase in mean arterial pressure on splanchnic and renal perfusion in a porcine
      model of volume-resuscitated endotoxic shock. DESIGN: Prospective, controlled,
      acute interventional study. SETTING: Animal research laboratory. SUBJECTS:
      Fourteen landrace pigs, seven treated with norepinephrine and seven used as
      endotoxemic controls. INTERVENTIONS: In an acute endotoxic shock model,
      norepinephrine was used to reverse hypotension in seven fluid-resuscitated pigs,
      anesthetized with alpha-chloralose and equipped with flow probes around the
      portal vein and renal artery, renal and jejunal mucosal laser Doppler flowmetry,
      and jejunal tonometry. Mean arterial pressure was increased by 10 and then 20 mm
      Hg above the shock level with norepinephrine. Seven shocked, fluid-resuscitated
      only animals served as the comparison group. MEASUREMENTS AND MAIN RESULTS:
      Measurements were performed before 2-hr endotoxin infusion and at the end of each
      increased level of mean arterial pressure. Raising mean arterial pressure with
      norepinephrine by 10 mm Hg significantly increased cardiac output, systemic
      oxygen extraction, and portal vein blood flow; stabilized metabolic acidosis; and
      tended to restore renal and jejunal mucosal flows to preshock levels. Increasing
      mean arterial pressure by 20 mm Hg further increased cardiac output and oxygen
      delivery but without improving portal vein, renal artery, and jejunal mucosal
      blood flows. CONCLUSIONS: Norepinephrine, administered to increase mean arterial
      pressure by 10 mm Hg in an acute model of volume-resuscitated endotoxic shock,
      improved systemic and regional perfusion. The administration of norepinephrine to
      increase mean arterial pressure 20 mm Hg above shock did not increase renal and
      splanchnic blood flows, despite an enhanced cardiac output.

PMID- 12072692
TI  - Changes in pulmonary function and oxygenation during application of
      perfluorocarbon vapor in healthy and oleic acid-injured animals.
AB  - OBJECTIVES: To investigate the changes in pulmonary function and gas exchange
      during application of 18% perfluorohexane vapor in healthy and in oleic acid
      injured animals and compare it with an injured control group. DESIGN: Prospective
      randomized controlled study. SETTING: Experimental research laboratory at a
      university medical center. SUBJECTS: Nineteen sheep weighing 31.4 +/- 4.1 kg.
      INTERVENTIONS: Lung injury was induced in 14 sheep by the intravenous injection
      of 0.1 mL/kg oleic acid. After establishment of lung injury (PaO(2)/F(IO(2))
      ratio, <200; pulmonary artery occlusion pressure, <19 torr), seven animals were
      treated with 18% perfluorohexane vapor for 30 mins whereas seven animals served
      as controls. After the start of perfluorohexane treatment, blood gases and
      respiratory and hemodynamic data were collected in 10-min intervals throughout
      the study period of 1 hr. In addition, five healthy animals received
      perfluorohexane vapor for 30 mins and were followed up for 2 hrs to exclude
      delayed negative effects. MEASUREMENTS AND MAIN RESULTS: Treatment of healthy
      animals with 18% perfluorohexane vapor was not accompanied by any significant
      adverse effects. It was associated with a significant decrease of alveolar
      arterial oxygen difference during perfluorohexane application (p <.05). In
      injured animals, 18% perfluorohexane led to a sustained improvement of peak
      inspiratory pressures within 10 mins of treatment (p <.001). The concomitant
      increase in compliance was equally significant (p <.001). Significant
      improvements in PaO(2) occurred despite a decrease in F(IO(2)) to 0.81 at the end
      of vaporization. CONCLUSION: Healthy animals tolerated perfluorohexane vapor well
      without significant changes in oxygenation and mechanical lung function for 2
      hrs. In injured animals, application of perfluorohexane vapor primarily improved
      peak inspiratory pressure and compliance. The increase of oxygenation therefore
      could be secondary to an improvement in compliance.

PMID- 12072693
TI  - Symptomatic vasospasm diagnosis after subarachnoid hemorrhage: evaluation of
      transcranial Doppler ultrasound and cerebral angiography as related to
      compromised vascular distribution.
AB  - OBJECTIVE: To evaluate the reliability of transcranial Doppler ultrasound in
      detecting symptomatic vasospasm in patients after aneurysmal subarachnoid
      hemorrhage and monitoring response after hypertensive and endovascular
      treatments. DESIGN: Retrospective chart review. SETTING: Neurosciences critical
      care unit in a tertiary-care university hospital. PATIENTS: All patients admitted
      to a neurosciences critical care unit with the diagnosis of subarachnoid
      hemorrhage between January 1990 and June 1997. INTERVENTIONS: None MEASUREMENTS
      AND MAIN RESULTS: We reviewed transcranial Doppler ultrasound data of 199
      patients; 55 had symptomatic vasospasm. Clinical symptoms and corresponding
      vascular distributions were identified, as was angiographic vasospasm (n = 35).
      The sensitivity and specificity of transcranial Doppler ultrasound for anterior
      circulation vessels were calculated by using a mean cerebral blood flow velocity
      criterion of >120 cm/sec. Clinical diagnosis of symptomatic vasospasm was used as
      the standard to determine sensitivity and specificity of transcranial Doppler
      ultrasound and cerebral angiography. The sensitivity of transcranial Doppler
      ultrasound for anterior circulation in patients with symptomatic vasospasm was
      73% with a specificity of 80%. The sensitivity of cerebral angiography was 80%.
      For individual vessels, the sensitivity and specificity of transcranial Doppler
      ultrasound were middle cerebral artery, 64% and 78%; anterior cerebral artery,
      45% and 84%; and internal carotid artery, 80% and 77%, respectively. The mean
      times for symptomatic and transcranial Doppler ultrasound signs of vasospasm
      presentation were 6.4 +/- 2 and 6.1 +/- 3 days, respectively. In patients without
      symptomatic vasospasm, the mean time for mean cerebral blood flow velocities >120
      cm/sec was 7.0 +/- 3 days (p <.05). Symptomatic vasospasm also was associated
      with thickness of clot on head computed tomography scan and rapidly increasing
      mean cerebral blood flow velocities. Transcranial Doppler ultrasound signs of
      vasospasm improved after endovascular treatment in 30 patients. CONCLUSIONS: The
      reliability of transcranial Doppler ultrasound was better at detecting high mean
      cerebral blood flow velocities in patients with symptomatic vasospasm related to
      middle cerebral and internal carotid artery distributions than for anterior
      cerebral artery distribution. Transcranial Doppler ultrasound was as sensitive as
      cerebral angiography at detecting symptomatic vasospasm. High mean cerebral blood
      flow velocities can be apparent before the presence of symptomatic vasospasm.
      Daily transcranial Doppler ultrasound monitoring could provide early
      identification of patients with aneurysmal subarachnoid hemorrhage who are at
      high risk for symptomatic vasospasm and may be helpful at following success of
      endovascular treatment.

PMID- 12072694
TI  - S100B protein is increased in asphyxiated term infants developing
      intraventricular hemorrhage.
AB  - OBJECTIVE: To establish whether S100B protein may be useful in the early
      detection of intraventricular hemorrhage in asphyxiated term infants. DESIGN:
      Case-control study. PATIENTS: Twenty full-term newborns with intraventricular
      hemorrhage, 20 asphyxiated infants without intraventricular hemorrhage, and 80
      normal newborns. INTERVENTIONS: Routine laboratory variables and neurologic
      patterns were assessed at birth after 12 and 72 hrs. Ultrasound imaging and
      middle cerebral artery Doppler velocimetry pulsatility index were recorded at 12
      and 72 hrs after birth. S100B protein blood concentrations were determined at 12
      hrs. MEASUREMENTS AND MAIN RESULTS: S100B protein levels were significantly
      higher in samples collected from newborns who developed intraventricular
      hemorrhage (1.87 +/- 0.60 microg/L) than from those who did not develop
      intraventricular hemorrhage (0.72 +/- 0.39 microg/L) or from normal infants (0.66
      +/- 0.31 microg/L). Multiple logistic regression analysis showed a significant
      correlation between circulating S100B protein concentrations and the occurrence
      of intraventricular hemorrhage. CONCLUSIONS: This study suggests that elevated
      S100B protein represents a useful tool for the early detection of
      intraventricular hemorrhage in the postasphyxia period when clinical examination
      and cerebral ultrasound might still be silent.

PMID- 12072695
TI  - Use of echocardiography for hemodynamic monitoring.
AB  - OBJECTIVE: To assess the accuracy of echocardiography for hemodynamic monitoring.
      DATA SOURCES: A computerized MEDLINE search was used with the following search
      headings: monitoring (physiologic and intra-operative) and both echocardiography
      and transesophageal echocardiography. A number of studies were obtained from the
      reference lists of cardiology reviews and textbooks. STUDY SELECTION: Studies
      that were designed to assess the accuracy of hemodynamic monitoring. DATA
      EXTRACTION: From the selected studies, the accuracy of different techniques for
      measuring preload and cardiac output was compared. DATA SYNTHESIS: Hypovolemia
      can be detected accurately by measuring left ventricular end-diastolic area. At
      high preload, Doppler-based methods are more accurate, although further studies
      in critical care patients are needed. Cardiac output is best measured by
      measuring Doppler flow, preferably across the aortic valve. CONCLUSIONS:
      Echocardiography can be used to make accurate hemodynamic measurements; however,
      training is required. Further studies are needed to validate these methods in the
      management of critically ill patients.

PMID- 12072696
TI  - Clinical practice parameters for hemodynamic support of pediatric and neonatal
      patients in septic shock.
AB  - BACKGROUND: The Institute of Medicine has called for the development of clinical
      guidelines and practice parameters to develop "best practice" and potentially
      improve patient outcome. OBJECTIVE: To provide American College of Critical Care
      Medicine clinical guidelines for hemodynamic support of neonates and children
      with septic shock. SETTING: Individual members of the Society of Critical Care
      Medicine with special interest in neonatal and pediatric septic shock were
      identified from literature review and general solicitation at Society of Critical
      Care Medicine Educational and Scientific Symposia (1998-2001). METHODS: The
      MEDLINE literature database was searched with the following age-specific
      keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary
      hypertension, nitric oxide, and extracorporeal membrane oxygenation. More than 30
      experts graded literature and drafted specific recommendations by using a
      modified Delphi method. More than 30 more experts then reviewed the compiled
      recommendations. The task-force chairman modified the document until <10% of
      experts disagreed with the recommendations. RESULTS: Only four randomized
      controlled trials in children with septic shock could be identified. None of
      these randomized trials led to a change in practice. Clinical practice has been
      based, for the most part, on physiologic experiments, case series, and cohort
      studies. Despite relatively low American College of Critical Care Medicine-graded
      evidence in the pediatric literature, outcomes in children have improved from 97%
      mortality in the 1960s to 60% in the 1980s and 9% mortality in 1999. U.S.
      hospital survival was three-fold better in children compared with adults (9% vs.
      27% mortality) in 1999. Shock pathophysiology and response to therapies is age
      specific. For example, cardiac failure is a predominant cause of death in
      neonates and children, but vascular failure is a predominant cause of death in
      adults. Inotropes, vasodilators (children), inhaled nitric oxide (neonates), and
      extracorporeal membrane oxygenation can be more important contributors to
      survival in the pediatric populations, whereas vasopressors can be more important
      contributors to adult survival. CONCLUSION: American College of Critical Care
      Medicine adult guidelines for hemodynamic support of septic shock have little
      application to the management of pediatric or neonatal septic shock. Studies are
      required to determine whether American College of Critical Care Medicine
      guidelines for hemodynamic support of pediatric and neonatal septic shock will be
      implemented and associated with improved outcome.

PMID- 12072697
TI  - Nitric oxide inhalation is useful in the management of right ventricular failure
      caused by myocardial infarction.
AB  - OBJECTIVE: To describe hemodynamic improvement in a patient treated with nitric
      oxide (NO) inhalation in the management of right ventricular failure caused by
      myocardial infarction. DESIGN: Case report. SETTING: An intensive care unit of a
      university hospital. PATIENT: A 66-yr-old man with severe right ventricular
      failure caused by acute myocardial infarction. INTERVENTIONS: Nitric oxide
      inhalation through a ventilator circuit. MEASUREMENTS AND MAIN RESULTS: The
      patient complained of chest pain. When myocardial infarction was diagnosed, he
      underwent percutaneous transluminal coronary angioplasty and percutaneous
      transluminal coronary recanalization, but they were not effective. We instituted
      intra-aortic balloon pumping and brought the patient to the intensive care unit
      (ICU). Even with high-dose inotropic support, his hemodynamics deteriorated
      gradually. On the patient's seventh day in the ICU, we started NO inhalation at 5
      10 ppm in an attempt to relieve his right heart failure. Immediately after NO
      inhalation was started, his hemodynamics improved significantly, and we could
      wean the patient from intra-aortic balloon pumping. NO inhalation was continued
      for 9 days and was successfully discontinued without circulatory deterioration.
      He was discharged from our hospital uneventfully. CONCLUSION: Nitric oxide
      inhalation improved hemodynamics in our patient with right ventricular failure
      after myocardial infarction. Our report suggests that a clinical trial of NO
      treatment for severe right ventricular failure caused by myocardial infarction is
      warranted.

PMID- 12072698
TI  - Cost effectiveness of aggressive care in nontraumatic coma.

PMID- 12072699
TI  - Pulmonary catheter fear factor.

PMID- 12072700
TI  - Ketamine vs. propofol: how safe is safe enough?

PMID- 12072701
TI  - Gastric prokinetic motility therapy to facilitate early enteral nutrition in the
      intensive care unit.

PMID- 12072702
TI  - Blood purification in sepsis: an idea whose time has come?

PMID- 12072703
TI  - Catheter replacement in patients on hemofiltration.

PMID- 12072704
TI  - Scoring of multiple organ dysfunction in patients with severe acute pancreatitis.

PMID- 12072705
TI  - Reversible myocardial dysfunction: an ubiquitous phenomenon in the critically
      ill?

PMID- 12072706
TI  - Yet another potential role for nitric oxide in the pathophysiology of septic
      shock.

PMID- 12072707
TI  - The alveolus and the capillary.

PMID- 12072708
TI  - When good cytokines go bad.

PMID- 12072709
TI  - An immune perspective on selective decontamination of the digestive tract.

PMID- 12072710
TI  - Norepinephrine administration in septic shock: how much is enough?

PMID- 12072711
TI  - Clinical practice parameters for pediatric and neonatal septic shock: to have or
      to have not?

PMID- 12072712
TI  - Oliguria: fluid deprivation or furosemide deficiency?

PMID- 12072714
TI  - A useful tool for predicting outcome for the pediatric head trauma patient.

PMID- 12072713
TI  - Why should paired blood cultures not be useful for diagnosing catheter-related
      bacteremia in critically ill patients?

PMID- 12072716
TI  - Changes of posterior corneal astigmatism and tilt after myopic laser in situ
      keratomileusis.
AB  - PURPOSE: The purpose of this study was to assess the changes of posterior corneal
      astigmatism and tilt after laser in situ keratomileusis (LASIK) and to correlate
      these changes with the amount of correction and the residual stromal bed
      thickness. METHODS: This prospective nonrandomized (self-controlled) comparative
      trial included 57 eyes from 14 females and 15 males, whose mean age (+/- standard
      deviation [SD]) at the time of surgery was 33 +/- 9 years (range, 19-53), with a
      spherical equivalent (SEQ) of -1.00 to -15.50 (mean, -5.07 +/- 2.81) diopters
      (D). All LASIK procedures were accomplished with the Keratom II Coherent-Schwind
      excimer laser and the Moria Model One microkeratome (150-microm head). Subjective
      refractometry, Orbscan slit-scanning corneal topography analysis, and pachymetry
      were performed before and 3 months after LASIK for myopia (n= 35; -1.00 to -15.50
      D [mean, -4.75 +/- 3.07]) or myopic astigmatism (n= 22; sphere, 0.00 to -9.75 D
      [mean, -4.75 +/- 2.36]; cylinder, -0.75 to -3.50 D [-1.68 +/- 0.86]). Intended
      ablation depth ranged from 12 to 108 (mean, 48 +/- 22) microm. Topographic raw
      data were decomposed into a set of Zernike polynomials as published in detail
      previously, and parameters for detection of asymmetric mechanical deformation of
      the cornea were derived. Posterior corneal astigmatism and tilt before and after
      LASIK were compared, and changes in these variables were correlated with the SEQ
      change (DeltaSEQ) and the residual corneal bed thickness (RBT). RESULTS: The RBT
      after LASIK ranged from 186 to 373 (mean, 280 +/- 42) microm. Overall,
      astigmatism (0.19 +/- 0.07 D/0.22 +/- 0.13 D; p= 0.80) and tilt (3.58 +/- 0.35
      degrees /3.65 +/- 0.48 degrees; p= 0.61) did not change significantly by 3 months
      after LASIK. In eyes with RBT < or =250 microm, the average change in astigmatism
      (0.05 +/- 0.11 versus 0.01 +/- 0.13 D; p= 0.46) and tilt (0.21 +/- 0.45 degrees
      versus 0.04 +/- 0.55 degrees; p= 0.30) was not greater than in eyes with RBT >
      250 microm. Change in astigmatism (p= 0.19) and tilt (p= 0.56) did not correlate
      with the RBT during LASIK. CONCLUSIONS: Zernike decomposition of topographic
      height data discloses that no significant asymmetric mechanical deformation of
      the posterior corneal curvature occurs after myopic LASIK. Further studies with
      long-term follow-up are needed to clarify whether this symmetry of the posterior
      corneal surface can indeed be preserved over time after LASIK if the RBT is < 250
      microm.

PMID- 12072718
TI  - Assessment of induced corneal hypoxia in diabetic patients.
AB  - PURPOSE: To assess the control of corneal hydration in patients with diabetes
      during a contact lens-induced hypoxia. METHODS: Corneal stress was induced in 15
      patients with diabetes and 23 healthy patients by having them wear contact lenses
      for 2 hours. Pachymetries were measured and corneal parameters (percentage
      recovery per hour [PRPH], time for deswelling [T99%] and induced swelling [IS])
      were calculated. In the mean time, tears were collected to assess the activity of
      lactate dehydrogenase (LDH), and a specular microscopy (SM) was performed.
      RESULTS: In patients with diabetes, PRPH, T99%, and LDH activity were
      statistically significantly modified (p < 0.05), whereas IS and SM were not.
      CONCLUSION: This decreased ability to recover the initial corneal thickness after
      a transient edema caused by hypoxia confirms the enzymatic dysfunction of the
      endothelial pumps that are partly caused by a shift toward anaerobic metabolism.

PMID- 12072717
TI  - Lysosomal hydrolase staining of conjunctival impression cytology specimens in
      keratoconus.
AB  - PURPOSE: This study sought to assess the feasibility of impression cytology for
      the determination of conjunctival intracellular lysosomal hydrolase (acid
      esterase) levels in patients with keratoconus. METHODS: Twenty-two patients with
      keratoconus currently enrolled in the Collaborative Longitudinal Evaluation of
      Keratoconus (CLEK) Study and 22 age-and sex-similar controls underwent impression
      cytology. Samples were collected from each subject and control pair on the same
      day. The cells of the respective specimens were fixed immediately and were
      stained for acid esterase with use of identical batches of fixatives and stains.
      After staining, the specimens were cleared in xylene for mounting in synthetic
      resin on glass slides. The acid esterase staining intensity of each specimen was
      quantified as the percentage of light transmitted with use of an image analysis
      system (Zeiss). Multiple cells from each specimen were analyzed for each sample
      collected. RESULTS: Mixed model analysis was used to account for the subject
      control pairings and for the multiple cells from each sample. With this method,
      the mean light transmission for normal controls (mean = 63.0; standard error [SE]
      = 3.0) was highly statistically significantly different from that for the
      keratoconus subjects (mean = 52.4; SE = 3.0) (two-tailed p= 0.0032). CONCLUSIONS:
      This study establishes the feasibility of adapting an acid esterase staining
      technique to conjunctival cells collected via impression cytology. Higher levels
      of lysosomal enzyme staining in patients with keratoconus have been previously
      reported by other investigators using full-thickness conjunctival specimens. We
      also demonstrate the value of using objective microspectrophotometry in measuring
      lysosomal enzyme staining with impression cytology specimens.

PMID- 12072719
TI  - Topographical analysis of corneal astigmatism in patients with tilted-disc
      syndrome.
AB  - PURPOSE: To evaluate the corneal topography in patients with tilted-disc syndrome
      to determine the relationship between optic disc dysversion and corneal
      astigmatism and the pattern of astigmatism in these patients. METHODS: The study
      included 23 eyes of the 13 tilted-disc syndrome patients with spheric refractive
      errors ranging between +1.00 D and -9.00 D (mean -4.00 +/- 3.4 D) and astigmatic
      errors ranging between -0.50 and -4.50 D (mean -1.95 +/- 0.93 D). Corneal
      topography was performed by computer-assisted videokeratoscope topographic
      modelling system 2 (TMS-2) and incidence of corneal astigmatism, corneal
      topographic patterns, and mean values of the topographic indices were determined.
      RESULTS: Corneal topographic analysis showed corneal astigmatism in 22 out of 23
      patients with tilted discs. Corneal astigmatism was symmetric bow tie pattern in
      10 eyes (45.45%), asymmetric bow tie pattern in 11 eyes (50%) and irregular in 1
      eye (4.5%). Among the patients with bow tie pattern group (21 eyes), 14 eyes had
      with-the-rule astigmatism, 1 eye had against-the-rule astigmatism, and 6 eyes had
      oblique astigmatism. In 18 eyes, astigmatism was corneal, whereas combined
      corneal and lenticular in 4 eyes and lenticular in 1 eye. CONCLUSION: In the
      majority of tilted-disc cases, ocular astigmatism is mainly corneal.
      Morphogenetic factors in the development of the tilted disc might possibly
      influence the corneal development in such a way to result in corneal astigmatism.

PMID- 12072720
TI  - Clinical, histopathologic, and ultrastructural characteristics of BIGH3(TGFBI)
      amyloid corneal dystrophies are supportive of the existence of a new type of LCD:
      the LCDi.
AB  - PURPOSE: To assess the morphologic differences of three types of lattice corneal
      dystrophies (LCDs) from histologic, immunohistochemical, and ultrastructural
      studies. METHODS: Corneas from three patients, one LCD1, one His626Arg-LCD, and
      one LCD3A were processed for Congo red, betaig-h3(541-564) antibodies
      immunostaining, and electron transmission microscopy studies. Control tissues
      were submitted to identical analyses and consisted of one cornea from a patient
      not having LCD and one skin biopsy from the patient suffering from LCD1. RESULTS:
      The three corneas displayed birefringent congophilic deposits under polarized
      light, confirming their amyloid nature. The deposits differed regarding their
      shape and location in each of the corneas. A strong immunoreactivity for betaig
      h3 was shown in the LCD1 and His626Arg-LCD deposits, which was faint for the
      LCD3A deposits. Ultrastructural analysis confirmed the dissimilarity of the
      deposits among the different types of LCD. No amyloid deposits were observed in
      the skin from the LCD1 patient, whereas immunostaining showed the presence of
      high amounts of betaig-h3. CONCLUSION: Our results show that betaig-h3 is
      involved in amyloid deposition in all the LCDs included in the study (LCD1,
      His626Arg-LCD, and LCD3A). These three forms of LCD, clinically different, were
      also distinguishable histologically, confirming that they belong to distinctive
      groups of LCDs. The absence of amyloid deposition in skin from the LCD1 patient
      supports cornea-specific amyloid formation. In light of the present clinical,
      histologic, and ultrastructural data, His626Arg and related LCDs constitute a
      separate group of LCD that could be considered as of intermediate type on
      clinical grounds.

PMID- 12072721
TI  - The performance of the contact lens dry eye questionnaire as a screening survey
      for contact lens-related dry eye.
AB  - PURPOSE: The contact lens dry eye questionnaire (CLDEQ) is a self-administered
      survey developed to examine the distribution of dry eye symptoms among contact
      lens wearers. In this report, we examine the CLDEQ as a screening survey for
      contact lens-related dry eye and compare it with McMonnies' questionnaire.
      METHODS: The CLDEQ and McMonnies' questionnaire were administered to 367
      unselected contact lens wearers at six clinics across the United States and
      Canada. After completion of the surveys, doctors unaware of the survey results
      completed a separate form indicating contact lens-related dry eye diagnosis at
      the end of a nondirected clinical examination. The CLDEQ is composed of nine
      habitual symptom subscales and a self-diagnosis question, which were tested for
      their predictive value for a diagnosis of contact lens-related dry eye.
      McMonnies' instrument was scored with use of the algorithm suggested in the
      literature. Sensitivity, specificity, and receiver operator characteristic (ROC)
      curve analyses were performed for each instrument on the basis of logistic
      regression results. RESULTS: The area under the ROC curve for the CLDEQ was 0.74,
      indicating moderate contact lens-related dry eye discrimination, and the Hosmer
      Lemeshow goodness-of-fit test indicated that the CLDEQ was well calibrated (p =
      0.84). The area under the ROC curve for McMonnies' questionnaire was 0.56,
      indicating poorer discrimination, and the Hosmer-Lemeshow goodness-of-fit test
      indicated it was also poorly calibrated (p = 0.08) for contact lens wearers.
      CONCLUSIONS: These analyses suggest that the CLDEQ is capable of discriminating
      contact lens-related dry eye and is accurate in doing so, especially in
      comparison with McMonnies' questionnaire. The CLDEQ is an efficient screening
      survey and may be used in future clinical research and epidemiologic studies of
      contact lens-related dry eye.

PMID- 12072722
TI  - Efficacy and safety of desonide phosphate for the treatment of allergic
      conjunctivitis.
AB  - PURPOSE: To study the safety and efficacy of the topical corticosteroid, desonide
      0.25% ophthalmic solution, for inhibition of the clinical allergic reaction
      induced by conjunctival provocation (CPT) and for the treatment of seasonal
      allergic conjunctivitis (SAC). METHODS: For the CPT study, 12 allergic but
      inactive patients were exposed in both eyes to increasing doses of a specific
      allergen until a positive bilateral, symmetrical early- and late-phase reaction
      was obtained. After 2 weeks the last positive dose was readministrated and their
      positive response confirmed. After an additional 2 weeks, CPT was performed 30
      minutes after topical administration of desonide in one eye and placebo in the
      contralateral eye (Group A) or after topical desonide or placebo four times a day
      for 2 days (Group B). Clinical signs and symptoms were recorded after 15, 30, and
      60 minutes, and after 6 hours. Regarding the seasonal study, 96 patients with
      active SAC were treated bilaterally with either desonide or fluorometholone for 3
      weeks, and allergic signs and symptoms evaluated at regular intervals. The safety
      of the drugs was assessed by identification of any side effects or adverse events
      of any kind. RESULTS: For the CPT study: individual itching and redness, and the
      sum score for signs and symptoms were all statistically (p < 0.05) and clinically
      (greater than 1 change between treated eyes) significantly lower in desonide
      versus placebo eyes. Both early- and late-phase reactions were reduced by
      desonide pretreatment. Seasonal study: desonide and fluorometholone were both
      highly effective in reducing itching, tearing, and conjunctival hyperemia over
      time (p < 0.0001). Both drugs appeared safe, with no statistically significant
      changes in IOP observed with either treatment. CONCLUSIONS: Desonide has a
      significant therapeutic effect on both the induced conjunctival early- and late
      allergic reaction and in active SAC. It was also safe, with no side effects such
      as increases in intraocular pressure observed by physician or patient.

PMID- 12072723
TI  - Histopathology of human corneas after amniotic membrane and limbal stem cell
      transplantation for severe chemical burn.
AB  - PURPOSE: To describe the histopathologic changes in the cornea following amniotic
      membrane transplantation (AMT) combined with limbal transplantation. METHODS:
      Four eyes with complete limbal stem cell deficiency after severe chemical burn
      underwent AMT with either a living-related conjunctival limbal allograft (lr
      CLAL) (three eyes) or a conjunctival limbal autograft (CLAU) (one eye) for ocular
      surface reconstruction. Penetrating keratoplasty was performed several months
      after the initial procedure for further visual rehabilitation. Mean follow up
      time was 20 months. Light and transmission electron microscopy (TEM) and indirect
      immunofluorescence microscopy of the excised corneal buttons were performed.
      RESULTS: All specimens displayed a multilayered epithelium without conjunctival
      goblet cells over the entire corneal surface. Basal epithelial cells demonstrated
      a firm connection to the remnants of the transplanted amniotic membrane (AM),
      which at some places appeared to be in a state of "modification" or "remodeling"
      in the collagen layers. The basement membrane zone displayed a positive staining
      when using antibodies against collagen IV and VII, integrin alpha6 and beta4,
      laminin 5, and bullous pemphigoid antigen 2. Remnants of the AM in the specimen
      showed staining of collagen IV, which was found also in cross-sections of
      cryopreserved AM. The recipients Bowman's membranes that were only partially
      present after the initial trauma were significantly disturbed. CONCLUSION: Within
      the time frame studied, the transplanted AM apparently survives and integrates
      into the host tissue being modified or remodeled by recipient cells. AMT in
      combination with a CLAU or lr-CLAL is a useful technique in promoting a rapid and
      stable reepithelialization of a corneal surface following severe chemical or
      thermal damage.

PMID- 12072724
TI  - Sterile structural imaging of donor cornea by optical coherence tomography.
AB  - PURPOSE: The purpose of the study was to demonstrate a new noncontact method for
      sterile measurement of structure and thickness of donor cornea with use of
      optical coherence tomography (OCT). METHODS: A commercially available OCT
      instrument designed for retinal measurements was used for noncontact assessment
      of human corneas. Structural changes occurring during organ culture were
      evaluated in 29 corneas. Comparison with histology was performed, and the ability
      of OCT to detect corneal scars and corneal thickness was investigated. RESULTS:
      Corneal epithelium, stroma, and posterior curvature, as well as thickness, can be
      measured by standard OCT while the cornea remains in its storage bottle.
      Epithelial changes leading to a reduction of epithelial thickness, stromal
      structural changes, and hydration folds can be visualized. OCT scans correlate
      well with histology. Preexisting and developing corneal scars can be detected by
      OCT. CONCLUSIONS: Corneal structural imaging can be performed under sterile
      conditions by OCT. This provides a method for improvement of corneal storage and
      a screening method for signs of photorefractive surgery and scarring in donor
      cornea.

PMID- 12072725
TI  - Ultraviolet light-induced changes in the glucose-6-phosphate dehydrogenase
      activity of porcine corneas.
AB  - PURPOSE: Corneas have the high activity of the pentose phosphate pathway. To
      clarify the relevance of the pentose phosphate pathway to their antioxidant
      defense, we examined the activity of glucose-6-phosphate dehydrogenase (G6PDH),
      the rate-determining enzyme of the pathway, in corneas exposed to ultraviolet
      light (UV). METHODS: Fresh porcine eye globes were exposed to ultraviolet light A
      (UVA) or ultraviolet light C (UVC), and the tear film-removed eye globes to UVA.
      After UV exposure, the corneas were dissected from the eye globes and extracted
      with a saline solution, and the G6PDH activity in the extract was assayed. The
      G6PDH activity of unilateral opaque corneas, their paired, transparent corneas,
      and normal corneas, all of which were obtained from fresh, UV-unexposed eye
      globes, and the L-lactate dehydrogenase (LDH) activity of these opaque and normal
      corneas also were assayed. RESULTS: The G6PDH activity of corneas increased with
      UVA exposure, and decreased with long-term UVC exposure, although it increased
      with short-term UVC exposure. A UV-blocking contact lens screened corneas from
      the UVA-induced increase. Removal of the tear film enhanced the UVC-induced
      decrease. The G6PDH activity of unilateral opaque corneas was lower than that of
      paired, transparent corneas or normal corneas, all of which were obtained from
      fresh, UV-unexposed eye globes. The LDH activity of the opaque corneas was much
      higher than that of the normal corneas. CONCLUSION: Exposure of corneas to UVA or
      a small dose of UVC enhances the G6PDH activity, i.e., the pentose phosphate
      pathway. This activity enhancement may play an important role in corneal
      antioxidant defense against UV-induced oxidative stress. However, exposure of
      corneas to large doses of UVC appears to damage the pathway.

PMID- 12072726
TI  - Superficial corneal effects of experimental nonmechanical penetrating
      keratoplasty using a Q-switched Er:YAG laser.
AB  - PURPOSE: To assess thermal effects of Q-switched Er:YAG laser trephination to
      corneal epithelium and superficial stroma using different mask types and
      materials for experimental penetrating keratoplasty. METHODS: Laser trephination
      was performed in 20 freshly-enucleated porcine eyes (repetition rate 5 Hz, pulse
      energy 65 mJ, spot size 0.7 mm). We used flat, open-metal and ceramic masks for
      donor and recipient trephination placed directly onto the corneal surface. Main
      outcome measures as assessed by light microscopy after PAS staining of 8-microm
      paraffin sections included: extension of tissue thermal damage at the cut edge in
      the superficial and basal epithelial layers, the basement membrane and
      subepithelial stroma, and depth and width of epithelial/stromal involvement in
      the area of the donor mask contact. RESULTS: The thermal damage in the
      superficial epithelium was more pronounced in donor (mean extension 61.6 +/- 15.6
      microm) than in recipient (29.4 +/- 24.9 microm, p= 0.05) trephination. In donor
      trephination, thermal damage zone of the superficial epithelial layer was
      significantly smaller with ceramic than with metal masks (21.0 +/- 23.0 versus
      61.6 +/- 15.6 microm, p= 0.014). In contrast, differences at basal epithelial
      layer (p= 0.44), basement membrane (p= 0.79), and subepithelial stroma (p= 0.2)
      were not statistically significant. Superficial donor involvement of the cornea
      adjacent to the paracentral donor mask contact zone was seen neither with ceramic
      nor with metal masks. CONCLUSION: Superficial corneal alterations adjacent to the
      mask-cornea contact zone may be minimized by using the Er:YAG laser in a Q
      switched mode. Ceramic masks, in contrast to metal masks, further reduce
      superficial thermal alterations at the cut edge.

PMID- 12072727
TI  - A fibrin-based bioengineered ocular surface with human corneal epithelial stem
      cells.
AB  - PURPOSE: The purpose of the investigation was to prepare a bioengineered ocular
      surface tissue replacement consisting of (presumed) human corneal epithelial stem
      cells in a cross-linked fibrin gel for potential transplant. METHODS: Presumed
      human epithelial stem cells were harvested, isolated, and cultivated as
      previously described from adult donor corneas obtained from a tissue and organ
      bank. The cultured corneal epithelial stem cells were suspended in a
      fibronectin/fibrin gel cross-linked by factor XIII. Plasma components were
      derived from a fibrinogen-rich cryoprecipitate of human plasma. Suspended cells
      proliferated in the fibrin gel, giving rise to colonies that eventually coalesced
      to near confluence over the 15 days of cultivation. The gels were sectioned and
      immunostained for keratin 3 (AE5) and keratin 19. RESULTS: The fibrin gel product
      with corneal stem cells was easily manageable and maneuverable. Addition of the
      protease inhibitor aprotinin to the incubation medium prevented gel degradation;
      once it was removed, gels disintegrated within 24 hours. All of the cells
      cultivated in the fibrin gel stained positively for keratin 3 (AE5), indicating
      differentiation along the corneal epithelium lineage. Cells located in the center
      of the colonies were keratin 19-positive, suggesting a more primitive cell type.
      Growth kinetics were documented. CONCLUSIONS: A bioengineered ocular surface with
      a combination of presumed corneal epithelial stem cells in a cross-linked fibrin
      gel represents a potential improvement in current attempts to create a
      transportable, pliable, and stable tissue replacement. Since both the cells and
      the plasma components of the fibrin gel are of human origin, this technique
      provides the potential for a totally autologous bioengineered replacement tissue.

PMID- 12072728
TI  - Adherence of two strains of Staphylococcus epidermidis to contact lenses.
AB  - PURPOSE: To compare the adherence of biofilm-producer and nonbiofilm-producer
      Staphylococcus epidermidis in vitro to different soft contact lenses (CLs) to
      study its possible contribution to the pathogenesis of keratitis. METHODS:
      Strains of S. epidermidis slime-positive ATCC 35984 (biofilm-producer) and slime
      negative ATCC 12228 (nonbiofilm-producer) were used with eight types of soft CLs
      from the four groups determined by the United States Food and Drug Administration
      (FDA), according to the ionicity and water content. The lenses were incubated
      overnight with the bacteria, then sonicated and vortexed to separate the adhered
      bacteria. Quantitative cultures were performed and the results statistically
      analyzed. RESULTS: Slime-negative strains of S. epidermidis were able to adhere
      to all CLs but at a lower level than slime-positive strains. There were
      significant differences in bacterial attachment among the four FDA groups. On the
      whole, there was higher bacterial adhesion to nonionic and low-water content
      materials. Contact lenses produced by soft molding were less adherent than CLs
      produced by either lathe-cutting or spin-casting. CONCLUSIONS: Bacterial biofilm
      favors bacterial adhesiveness and colonization of soft CLs. Bacterial attachment
      was less in soft molding CLs (etafilcon A), which provide a more homogeneous and
      smoother surface.

PMID- 12072729
TI  - Severe keratomycosis secondary to Scedosporium apiospermum.
AB  - PURPOSE: To report an unusual case of severe keratomycosis caused by Scedosporium
      apiospermum without any known previous ocular injury, that resulted in a corneal
      perforation, which was treated with an emergency penetrating tectonic
      keratoplasty and later with phacoemulsification and astigmatic keratotomy to
      restore good visual function. METHODS: A 45-year-old woman with a history of
      multiple sclerosis presented with a severe and refractory corneal abscess in her
      right eye without any known prior injury. Corneal scrapings were obtained and
      stained for microscopic evaluation. The samples were sent for aerobic and
      anaerobic bacterial and fungal cultures. RESULTS: Microbiologic examination of
      the corneal scraping showed Scedosporium apiospermum micelle. The fungal culture
      was sensitive to miconazole, itraconazole and voriconazole. Partial clinical
      improvement was achieved with hourly topical natamycin, amphotericin B, and
      systemic itraconazole application, although in vitro sensitivity tests showed
      resistance to the topical antifungal agents used. A corneal paracentral
      perforation occurred despite aggressive treatment. An emergency eccentric
      penetrating keratoplasty was performed with satisfactory results. Subsequent
      phacoemulsification and astigmatic keratotomy restored a good visual function.
      CONCLUSION: A fungal etiology should be suspected in a progressive and refractory
      corneal abscess. This report highlights the utility of microbiologic
      investigation to perform an early and accurate diagnosis. Aggressive medical
      treatment and even therapeutic penetrating keratoplasty to remove infected tissue
      could result in the maintenance of useful visual function. In view of the poor
      prognosis of this specific fungus, a closer observation and early keratoplasty
      might be required to preserve the ocular globe.

PMID- 12072731
TI  - Subepithelial amyloid deposits in congenital hereditary endothelial dystrophy: a
      histopathologic study of five cases.
AB  - PURPOSE: To report the clinical, histologic, ultrastructural, and
      immunohistochemical features of congenital hereditary endothelial dystrophy
      (CHED) associated with subepithelial amyloid deposits. METHODS: The clinical
      features of seven patients and histologic characteristics of eight corneal
      buttons were evaluated. The corneal specimens included five cases with histologic
      features of CHED associated with subepithelial amyloid. The remaining three
      corneal buttons of CHED without amyloid were obtained from the fellow eye of an
      affected patient and from siblings of two affected patients. Light microscopic
      studies were performed on sections stained with hematoxylin and eosin, periodic
      acid Schiff stain, and Congo red stain with and without permanganate bleach.
      Immunohistochemistry with an antibody to the amyloid AA protein and lambda and
      kappa light chains was done on all specimens. Electron microscopy was performed
      on three corneal specimens. The cases were followed for 1-9 years. RESULTS: The
      notable clinical findings included decreased vision, history of parental
      consanguinity (4/7 cases), and affected siblings (5/7 cases). Examination
      revealed nystagmus (5/7 cases) and bilateral ground-glass corneas in all
      patients. In addition, central subepithelial whitish opacities were noted in
      patients with CHED and amyloid. Three patients had associated congenital
      glaucoma. The patients underwent penetrating keratoplasty at a mean age of 10
      years. Histologically, five corneal buttons of CHED revealed varying degrees of
      subepithelial amyloid deposits associated with a subepithelial fibrous pannus.
      Immunohistochemically, the deposits were nonreactive to anti-amyloid A antibody
      but were immunoreactive with an antibody to lambda light chains in two cases.
      Electron microscopy confirmed the presence of subepithelial amyloid. Thickening
      of Descemet's membrane and attenuation of corneal endothelial cells, noted in all
      cases, was consistent with features of CHED. The corneal buttons from the fellow
      eye and the siblings showed histologic features of CHED, with a subepithelial
      fibrous pannus without amyloid deposits. Spheroidal degeneration was noted in two
      corneal specimens. To date, no recurrence of the amyloid deposits has been seen
      in the grafts. CONCLUSIONS: This study demonstrates that subepithelial
      amyloidosis may be rarely associated with a recessive form of congenital
      hereditary endothelial dystrophy. The clinical, histologic, and
      immunohistochemical features suggest a secondary form of amyloidosis.

PMID- 12072730
TI  - Fungal keratitis caused by Scedosporium apiospermum: report of two cases and
      review of treatment.
AB  - PURPOSE: We report our experience in treating two cases of Scedosporium
      apiospermum keratitis and provide a review of basic scientific and clinical data
      regarding the treatment of this visually devastating disease. METHOD: We present
      a case report and literature review. RESULTS: A 35-year-old woman and a 73-year
      old man both reported pain, redness, and a foreign body sensation in the eye
      after trauma. They were initially treated with antibacterials. When cultures were
      positive for S. apiospermum, the first patient was treated with fluconazole and
      amphotericin with good results. The second was treated with fluconazole and
      natamycin, but the infection persisted and the eye was eventually enucleated.
      Review of the literature showed variable responsiveness of S. apiospermum to
      antifungal treatment. CONCLUSIONS: It is difficult to predict how S. apiospermum
      keratitis will respond to treatment, but miconazole appears to be useful in
      conjunction with other antifungals. Voriconazole shows promise as an effective
      alternative.

PMID- 12072732
TI  - Acute scleritis as a manifestation of congenital erythropoietic porphyria.
AB  - PURPOSE: To report a case of congenital erythropoietic porphyria that presented
      as acute scleritis over a bilateral scleromalacia perforans in the interpalpebral
      fissure. METHODS: An 18-year-old man presented with painful red eye, a history of
      photophobia, and passing highly colored urine since childhood. Dermatological and
      biochemical evaluations were done. RESULTS: The patient had normal vision in both
      eyes with bilateral scleromalacia perforans. The right eye showed painful,
      nodular scleritis. Dermatological examination revealed multiple, vesciculobullous
      cutaneous lesions with atrophy and pseudoscleroderma changes, hypertrichosis, and
      bluish discoloration of teeth. Immunofluorescent microscopy of fresh peripheral
      smear showed brilliant red fluorescence of erythrocytes. Spectroscopic analysis
      of urine revealed excretion of porphyrin, thus confirming a diagnosis of
      congenital erythropoietic porphyria. The patient's condition improved with local
      and systemic steroid therapy along with general photoprotective measures for the
      exposed parts of the body. CONCLUSION: Acute scleritis could be the presenting
      feature in a rare case of congenital erythropoietic porphyria, warranting
      systemic evaluation.

PMID- 12072733
TI  - Fungal keratitis after nonpenetrating glaucoma surgery.
AB  - PURPOSE: The purpose was to report a case of fungal keratitis that occurred
      following viscocanalostomy. METHODS: A 63-year-old man who underwent
      viscocanalostomy in his left eye presented with pain, redness, watering, and a
      decrease in visual acuity. Slit lamp examination showed teardrop-like stromal
      infiltration of the superior cornea. Corneal and conjunctival scrapings were
      obtained and a corneal biopsy was performed. RESULTS: Microscopic examination of
      smears demonstrated no bacteria and fungi. Corneal biopsy revealed dichotomously
      branching, septate hyphae suggestive of Aspergillus species. Culture identified
      no microorganism. The patient responded to amphotericin B treatment and the
      corneal infiltration resolved, leaving a plaquelike corneal scar. CONCLUSION:
      Fungal keratitis may occur after viscocanalostomy, but prompt diagnosis and
      treatment can preserve the eye.

PMID- 12072734
TI  - Hydrops in a corneal graft.

PMID- 12072735
TI  - Broadening our outlook on sources for corneal donation.

PMID- 12072736
TI  - Reply to Deep lamellar keratoplasty as surgical management of anterior and
      posterior segment injuries to the eye.

PMID- 12072741
TI  - On the articulations. The genuine works of Hippocrates.
AB  - From The Genuine Works of Hippocrates, Baltimore, Wilkins & Wilkins 205-214,
      1939. Francis Adams, translator.

PMID- 12072737
TI  - Penetrating keratoplasty using tissue from a donor with previous LASIK surgery.

PMID- 12072742
TI  - Variation in the glenoid origin of the anteroinferior glenohumeral capsulolabrum.
AB  - Restoration of the anteroinferior capsulolabrum, including the labrum and origin
      of the anterior band of the inferior glenohumeral ligament is crucial during
      Bankart repair. The purpose of the current study was to describe variations in
      this anatomy near the glenoid. The histologic and gross anatomy were studied in
      10 fresh-frozen glenohumeral joints from adult cadavers. Each joint was placed in
      the apprehension position of abduction, external rotation, and horizontal
      abduction because anterior dislocation occurs in this shoulder position. The
      joints then were sectioned serially in the transverse plane from cephalad to
      caudad. Three glenohumeral joints were embedded in Techovit 7200 resin,
      polymerized, and then mounted onto an acrylic slide. Ground sections were
      prepared by attaching a microscope slide to the face of each and cutting 200
      microm-thick sections. The thin sections were ground to a thickness of 30 microm.
      Finally, sections were stained with 1% toluidine blue zero in 1% sodium
      tetraborate for light microscopic examination. The other seven glenohumeral
      joints were frozen in the apprehension position and held with a custom jig while
      sectioned serially at 3-mm intervals. The surfaces then were recorded with a
      tabletop computer and a scanning device. Two distinct patterns of the
      anteroinferior capsulolabrum attachment to the glenoid were identified. In eight
      joints (80%) it had its major origin from the labrum with some fibers extending
      onto the glenoid neck, a Type I origin. In two joints (20%), it emanated solely
      from the glenoid neck, a Type II origin. Failure to repair the glenoid origin of
      the anteroinferior capsulolabrum, the location of the anterior band of the
      inferior glenohumeral ligament, because of variations in its anatomy may be a
      reason for failure after Bankart repair.

PMID- 12072743
TI  - Anatomy and function of the glenohumeral ligaments in anterior shoulder
      instability.
AB  - The anatomy of the glenohumeral ligaments has been shown to be complex and
      variable and their function is highly dependent on the position of the humerus
      with respect to the glenoid. The superior glenohumeral ligament with the
      coracohumeral ligament was shown to be an important stabilizer in the inferior
      direction, even though the coracohumeral ligament is much more robust than the
      superior glenohumeral ligament. The middle glenohumeral ligament provides
      anterior stability at 45 degrees and 60 degrees abduction whereas the inferior
      glenohumeral ligament complex is the most important stabilizer against
      anteroinferior shoulder dislocation. Therefore, this component of the capsule is
      the most frequently injured structure. An appropriate surgical procedure to
      repair the inferior glenohumeral ligament complex after shoulder dislocation must
      be considered. In addition, a detached labrum can lead to recurrent anterior
      instability and a compromised inferior glenohumeral ligament complex. However,
      additional capsular injury usually is necessary to allow anterior dislocation.

PMID- 12072744
TI  - Dynamic glenohumeral stability provided by three heads of the deltoid muscle.
AB  - The deltoid is a large bulky muscle, comprising approximately 20% of the shoulder
      muscles. Therefore, the function of the deltoid as a stabilizer is thought to be
      significant. The current authors quantified dynamic glenohumeral stability
      provided by three heads of the deltoid by a new biomechanical parameter, the
      dynamic stability index. The dynamic stability index considers not only the force
      vectors generated by individual shoulder muscle, but also the concavity
      compression mechanism. The higher the dynamic stability index, the greater the
      dynamic stability. The deltoid generated significant shear force and compressive
      force in the position of anterior shoulder instability. The deltoid provided
      dynamic stability with the arm in the scapular plane and only decreased the
      stability of the shoulder with the arm in the coronal plane. The mid and
      posterior heads should be strengthened vigorously in anterior shoulder
      instability in conservative and operative treatment, because they provide more
      stability generating higher compressive force and lower shear force than the
      anterior head. Scapular muscles should be balanced to avoid the vulnerable
      glenohumeral position where the arm is extended beyond the scapular plane.
      Anatomic reattachment of the detached labrum onto the glenoid rim in the anterior
      instability is important to enhance the effect of compressive force component
      generated by the muscles.

PMID- 12072745
TI  - Interplay of the static and dynamic restraints in glenohumeral instability.
AB  - Anterior glenohumeral instability is a common, yet complicated orthopaedic
      disorder. During the past few years, basic science research has improved the
      understanding of the glenohumeral joint stabilizing systems. The current authors
      review new contributions specifically detailing study of the interplay between
      the static and dynamic restraints. Simulation of the shoulder muscles in a recent
      study also has manifested the powerful contribution of the joint reaction force
      to concavity-compression. Continued advances, such as these, will improve the
      understanding, and allow better outcome, in treatment of glenohumeral
      instability.

PMID- 12072746
TI  - Open surgical repair restores joint forces that resist glenohumeral dislocation.
AB  - Traumatic anterior shoulder instability is a clinical problem often observed in
      athletes participating in overhead activities. The standard treatment for this
      condition is surgical repair, which may be accomplished by an open or
      arthroscopic procedure. The current authors assessed the strength of open repair,
      by comparing glenohumeral joint forces in intact specimens with specimens with
      anterior dislocation and open repair. Eighteen shoulders from cadavers were
      tested on a custom shoulder dislocation device with simulated muscle forces.
      Bankart lesions were repaired using a three-suture anchor technique combined with
      capsular advancement. Capsular failures were addressed by sharp dissection of the
      labrum from bone, then repaired as above, and the experiment was repeated. One
      way analysis of variance was used for analyses. All specimens dislocated
      anteroinferiorly, eight dislocated by bony Bankart failure, and 10 dislocated by
      capsular failure. Maximum joint compression force for the initial dislocation was
      760 +/- 79 N for the specimens with Bankart failures and 690 +/- 59 N for the
      specimens with capsular failures. The maximum joint compression force for
      dislocation after repair measured 541 +/- 50 N for the specimens with Bankart
      failures and 536 +/- 46 N for the specimens with capsular failures. The forces
      after repair were normalized with respect to the intact shoulders. For specimens
      with Bankart failures, joint compression and pectoralis major forces were 72% and
      62%, respectively, and 79% and 61% for specimens with capsular failures. A three
      dimensional digitizing system confirmed restoration of glenohumeral position.
      These results support clinical data, showing that open Bankart repair adequately
      restores the static restraints of the glenohumeral joint that resist
      anteroinferior dislocation.

PMID- 12072748
TI  - Disorders of the superior labrum: review and treatment guidelines.
AB  - Advancements in shoulder arthroscopy have led to a better understanding of the
      anatomy and disorders of the superior labrum biceps tendon anchor complex and the
      role that lesions of the superior labrum anterior and posterior lesions play in
      pain and instability of the shoulder. Various injury mechanisms have been
      suggested and studied and it is likely that different mechanisms produce
      different types and areas of damage to the superior labrum. Classification
      systems have been proposed to describe the specific pathoanatomy of lesions of
      the superior labrum anterior and posterior lesions and to guide treatment.
      Presenting symptoms often are nonspecific and physical examination maneuvers have
      varying degrees of sensitivity and specificity making diagnosis challenging.
      Diagnostic ability is enhanced by the ultimate diagnostic test, arthroscopy. A
      clear appreciation for the various lesions and the potential resulting joint
      dysfunction is necessary to determine the appropriate treatment of this complex
      region of the shoulder. The current authors review the anatomy, classification,
      presentation, evaluation and treatment results of superior labrum anterior and
      posterior lesions, and includes novel evaluation methods and treatment guidelines
      useful in treating these lesions.

PMID- 12072747
TI  - Classification of glenohumeral joint instability.
AB  - Shoulder instabilities have been classified according to the etiology, the
      direction of instability, or on combinations thereof. The current authors
      describe a classification system, which distinguishes between static
      instabilities, dynamic instabilities, and voluntary dislocation. Static
      instabilities are defined by the absence of classic symptoms of instability and
      are associated with rotator cuff or degenerative joint disease. The diagnosis is
      radiologic, not clinical. Dynamic instabilities are initiated by a trauma and may
      be associated with capsulolabral lesions, defined glenoid rim lesions, or with
      hyperlaxity. They may be unidirectional or multidirectional. Voluntary
      dislocation is classified separately because dislocations do not occur
      inadvertently but under voluntary control of the patient.

PMID- 12072749
TI  - Cadaveric study of glenohumeral translation using electromagnetic sensors.
AB  - Clinical methods for measuring shoulder translation rely heavily on the
      experience of the examiner and remain largely subjective, prone to errors of
      interobserver and intraobserver reproducibility. Accurate in vitro methods of
      measuring glenohumeral translation exist. The purpose of the current study was to
      evaluate the accuracy of computerized electromagnetic spatial sensors applied to
      the skin, in measuring glenohumeral translation under simulated conditions of a
      standard shoulder examination. Seven thawed, fresh-frozen shoulder specimens from
      cadavers were used in the study. Soft tissue and skin were not removed. The
      specimens were mounted to simulate clinical positions of patients having an
      anteroposterior drawer or load-and-shift test. A series of anterior and posterior
      displacements were done manually under two conditions. Condition I:
      Electromagnetic position sensors were taped to skin and held beneath the
      examiner's fingers; and Condition II: Sensors were fixed rigidly to pins inserted
      into the glenoid and humeral head, respectively. Displacement values between
      conditions, within trials, and among specimens were compared for accuracy and
      reproducibility. Strong agreement was shown between Condition I and Condition II
      for the anterior and posterior directions (interclass correlation coefficients
      0.81 and 0.86, respectively). Simple linear regression revealed a significant
      association between conditions in the anterior and posterior directions.
      Reproducibility between trials under each condition was extremely high, with
      interclass correlation coefficients greater than or equal to 0.98 regardless of
      direction of displacement or testing condition. The data from the current study
      show that cutaneous application of electromagnetic position sensors to the
      shoulder can accurately and reproducibly measure true glenohumeral translation
      under testing conditions that mimic a standard, clinical shoulder examination.

PMID- 12072750
TI  - Quantitative assessment of glenohumeral translation.
AB  - Cutaneous electromagnetic position sensors were used to quantify anteroposterior
      laxity of the shoulder. Forty-three female athletes were tested (27 were soccer
      players and 16 were swimmers). The athletes had a mean age of 18.8 years (range,
      17-24 years), and all were free of shoulder disorders. Dominant and nondominant
      shoulders were tested. Each shoulder was suspended in 90 degrees abduction and
      neutral rotation. Serial anteroposterior translations were done manually similar
      to an anteroposterior drawer examination of the shoulder. The glenohumeral
      translation for the soccer players was 9.6 mm (range, 5.8-15.1 mm) in the
      dominant shoulder and 10.7 mm (range, 5.2-16.7 mm) in the nondominant shoulder.
      The translations in the swimmers were significantly greater at 12.4 mm (range,
      8.9-15.9 mm) in the dominant and 13.8 mm (range, 8.8-17.4 mm) in the nondominant
      shoulders. The mean of the differences between the dominant and nondominant
      shoulders was 2.1 mm for the swimmers and soccer players. For the soccer players,
      the range for the side to side differences was 0.1 to 5.3 mm. For the swimmers,
      the range was 0.1 to 4.3 mm. Finding a clinical device for objective measurement
      of joint laxity in the shoulder that is accurate, reproducible, noninvasive, and
      easy to use has been evasive.

PMID- 12072751
TI  - Sensorimotor deficits contributing to glenohumeral instability.
AB  - The conventional perspective has been that capsuloligamentous structures act as a
      mechanical restraint to humeral translation at the shoulder. Although this is
      true, the capsuloligamentous structures also have a sensorimotor influence on the
      musculoskeletal system, providing stability at the shoulder. The purpose of the
      current study was to discuss the sensorimotor role that the capsuloligamentous
      structures play in providing stability, how these mechanisms are disrupted with
      glenohumeral instability, and how surgical intervention restores such mechanisms.
      Proprioceptive information transmitted from the mechanoreceptors embedded within
      the capsuloligamentous structures influence the coordinated motor patterns,
      reflex activity, and joint stiffness to provide enhanced joint stability. The
      capsuloligamentous injury that occurs with shoulder instability not only affects
      mechanical restraint, but also alters this proprioceptive input to the central
      nervous system. As a result of these deficits in proprioception, alterations in
      reflex activity and motor programs as evident by muscle firing pattern
      alterations manifest. Although the main goal of surgical intervention is to
      restore the mechanical restraint that is lost with joint dislocation or
      subluxation, surgical intervention whether through open, arthroscopic, or thermal
      techniques seem to restore the proprioceptive deficits that exist after joint
      injury.

PMID- 12072752
TI  - Thermal capsulorrhaphy to treat shoulder instability.
AB  - The contemporary therapeutic approach of glenohumeral instability is directed at
      the restoration of anatomy. Thermal capsular modification to treat shoulder
      instability is a relatively recent modality. Early successful clinical
      applications have led to a wide use of this low demanding technique. Currently,
      however, the indications for thermal capsulorrhaphy are defined poorly, clinical
      outcome has not been shown to be superior to conventional stabilization
      procedures, and long-term effects on joint biology and mechanics are not known.
      Based on a critical review of the literature and personal clinical experience,
      the authors conclude that additional experimental and clinical investigations are
      necessary to add this procedure to the accepted modalities applied for the
      treatment of shoulder instability.

PMID- 12072753
TI  - Recent advances in arthroscopic repair of traumatic anterior glenohumeral
      instability.
AB  - Traumatic anterior instability is the most common type of glenohumeral
      instability. Although surgical treatment with an open technique has produced
      excellent results, there has been a trend toward arthroscopic treatment. As
      understanding of instability advances along with improvements in surgical
      techniques and instrumentation, arthroscopic results are fast approaching those
      seen with open procedures. Studies done at the authors' institution showed a 97%
      satisfactory outcome at short-term followup with 93% stable shoulders in a
      patient population with high physical demands. Others recently reported similar
      results. As more surgeons become familiar with the techniques, it is thought that
      arthroscopic Bankart reconstructions will be the preferred method in the future.

PMID- 12072754
TI  - Importance of a radial head component in Sorbie unlinked total elbow
      arthroplasty.
AB  - The effects of a radial head component on total elbow arthroplasty kinematics and
      stability were evaluated using an anatomic design unlinked total elbow
      prosthesis. An electromagnetic tracking device recorded motion and varus and
      valgus displacements under various conditions in 10 cadaveric elbows. The motion
      patterns of the intact elbows and the Sorbie-Questor total elbow prostheses with
      a radial head component were similar, as both tended to have a valgus position in
      extension, varus at midflexion, and more valgus toward full flexion. Under
      conditions of simulated muscle loading, the maximum valgus and varus laxity of
      the elbow prosthesis was, on average, 8.6 degrees +/- 4.0 degrees greater than
      normal. Without the radial head component, however, significant kinematic
      disturbances and instabilities were seen. The varus and valgus displacements were
      13.3 degrees +/- 5.5 degrees greater than the intact elbows. One total elbow
      arthroplasty without a radial head dislocated during testing. Increasing the
      muscle loading across the elbow significantly enhanced dynamic stability of the
      total elbow arthroplasties, especially in the extension half of elbow motion
      where instability is greatest. However, this dynamic enhancement of stability was
      seen only in those elbows in which the radial head component had been implanted.
      The radial head component is an important stabilizer, particularly in extension
      for this prosthesis, and possibly for other unlinked total elbow prostheses.
      Although instability of unlinked prostheses depends on the prosthetic design, the
      use of a radial head replacement may be an important factor in preventing such
      instability. Perhaps even more importantly, a radial head component balances the
      load distribution across the articulation, which could decrease stress on the
      ulnohumeral articulation and therefore possibly reduce polyethylene wear,
      osteolysis, and loosening.

PMID- 12072755
TI  - Spine behavior caudal to instrumentation in King II and IV curves.
AB  - This retrospective review of children surgically treated for King Type II or IV
      curvature of the spine required a minimum lumbar Cobb angle of 40 degrees and a
      minimum lumbar inclination (the angle formed between a line through the spinous
      processes of the three most caudal lumbar vertebrae and a line perpendicular to
      the floor) of 10 degrees. Twenty children had combined anterior thoracolumbar and
      posterior instrumentations whereas 20 had only posterior instrumentation.
      Children who had combined surgery had significantly better corrections of their
      lumbar Cobb angles. They had a mean correction of 43.3 degrees compared with 26.7
      degrees in children with posterior instrumentation only. These superior
      corrections of the lumbar Cobb angles did not result in significantly better
      improvements in the lumbar inclinations. Patients who had the combined procedures
      had a mean improvement of 10.1 degrees, whereas patients who had posterior
      instrumentation only had a mean improvement of 8.0 degrees in lumbar inclination.
      Instead of having superior corrections of the lumbar inclinations, the combined
      surgeries resulted in a significant worsening of the angle between the end plates
      of the last instrumented vertebra and the next most caudal end plate. In patients
      who had combined surgery this angle averaged 8.4 degrees, whereas in patients who
      had posterior instrumentation only this angle averaged 4.1 degrees.

PMID- 12072756
TI  - The fate of revised uncemented acetabular components in patients with rheumatoid
      arthritis.
AB  - The results of patients with rheumatoid arthritis who had revision hip
      arthroplasty have been studied infrequently. The purpose of this study was to
      review the authors' clinical and radiographic experiences and outcomes with
      revision hip arthroplasty. Revision total hip arthroplasties were done on 28
      patients (30 hips). All hips had morselized bone grafting and four hips had bulk
      allografts for segmental defects. The mean age of the patients at the time of
      surgery was 50 years (range, 20-74 years). Patients were followed up for 4 to 15
      years (mean, 7 years). At the latest followup, 14 hips (13 patients) of the 30
      hips (47%) had good and excellent Harris hip score ratings. Mechanical failures
      included six hips (five patients) that had revision arthroplasty and two hips
      (two patients) that had resection arthroplasty. Six other hips (five patients)
      had poor Harris hip score ratings. The Kaplan-Meier survivorship curve for
      failure of the acetabular component revealed an 89% chance of survivorship curve
      for failure of the acetabular component revealed an 89% chance of survival at 60
      months and a 44% chance of survival at 108 months. Based on the results of this
      study, revision hip arthroplasty for acetabular loosening with a cementless
      acetabular prosthesis has a low rate of success in patients with rheumatoid
      arthritis.

PMID- 12072757
TI  - Progression and cessation of collapse in osteonecrosis of the femoral head.
AB  - Thirty-five patients (54 hips) with osteonecrosis of the femoral head without
      collapse or only with a crescent sign were followed up for at least 5 years to
      clarify the natural course of osteonecrosis. During the followup, 28 hips (52%)
      in 21 patients collapsed including nine hips in nine patients with small necrotic
      lesions occupying less than the medial (2/3) of the weightbearing area. Cessation
      of collapse then was observed in 15 (14 patients) of the 28 hips (54%),
      especially in eight of the nine hips (89%) with small necrotic lesions. Of the 15
      hips in 14 patients with cessation of collapse, 11 hips (73%) in 11 patients had
      less than 2 mm collapse and 10 hips in nine patients became asymptomatic. The
      analysis indicated that collapse of the femoral head does not necessarily
      determine a poor prognosis, and even after collapse occurs, subsequent cessation
      of collapse can be expected in a certain percentage of hips. Hips with less than
      2 mm collapse and necrotic lesions occupying less than the medial (2/3) of the
      weightbearing area have a high chance of cessation of collapse and improvement of
      symptoms with no surgical intervention.

PMID- 12072758
TI  - Intraoperative electromyographic monitoring during periacetabular osteotomy.
AB  - Periacetabular osteotomy has become the procedure of choice in many centers for
      the treatment of symptomatic hip dysplasia. Intraoperative real-time nerve
      monitoring has been advocated during acetabular fracture repair and complex total
      hip arthroplasties to prevent iatrogenic sciatic nerve injury. To the authors'
      knowledge there is no information concerning the use of intraoperative
      electromyographic monitoring during periacetabular osteotomy. The purpose of the
      current study was to investigate the use of intraoperative continuous
      electromyographic monitoring during periacetabular osteotomy in a relatively
      large consecutive series of patients as a mechanism to prevent nerve injury
      during surgery and as a prognostic indicator of neurologic function after
      periacetabular osteotomy. From September 1992 to July 1999, 140 consecutive
      periacetabular osteotomies were done in 127 patients at the authors' institution.
      There were 96 females and 31 males, with an average age of 32 years at the time
      of surgery. All patients had intraoperative electromyographic monitoring of
      femoral and sciatic innervated muscles. All patients were followed up for a
      minimum of 1 year, until complete resolution of neurologic deficits, or both.
      Thirty-six patients (26%) had abnormal electromyographic activity recorded during
      surgery. Seven patients (5%) had peroneal nerve deficits postoperatively
      including extensor hallucis longus and tibialis anterior weakness with loss of
      sensation in the first web space. Abnormal electromyographic activity was
      observed intraoperatively in five of the seven patients with postoperative
      deficits. Six of the seven injuries resolved completely. One patient with
      intraoperative electromyographic activity (0.7%) had a postoperative foot drop
      that persisted for greater than 1 year. There were no femoral, tibial, or
      obturator nerve deficits observed. Electromyographic monitoring appears to
      provide prediction of postoperative neurologic deficit.

PMID- 12072759
TI  - Histologic evaluation of posterior cruciate ligaments from osteoarthritic knees.
AB  - It is controversial whether posterior cruciate ligament-retaining or posterior
      cruciate ligament-sacrificing (-substituting) implants should be used in total
      knee arthroplasty. The use of posterior cruciate ligament-retaining implants
      implies that the residual ligament is functional, and presumably normal, but few
      studies have been conducted to elucidate the histologic appearance of the
      posterior cruciate ligament taken from osteoarthritic knees. The purposes of the
      current study were (1) to evaluate the histologic appearance of posterior
      cruciate ligaments excised from osteoarthritic knees during primary total knee
      arthroplasty and to compare their appearance with posterior cruciate ligaments
      from knees of cadavers that were not operated on; and (2) to determine whether a
      correlation exists between the histologic appearance of the posterior cruciate
      ligament and the clinical status of the patients studied. Twenty-six posterior
      cruciate ligament specimens from patients with osteoarthritis and four specimens
      from cadavers were evaluated with the use of light and electron microscopy.
      Posterior cruciate ligaments from osteoarthritic knees showed greater
      degeneration than those from cadavers by light microscopy. Age greater than 60
      years was associated with decreased collagen diameter in posterior cruciate
      ligaments from osteoarthritic knees as determined by electron microscopy. With
      the number of specimens available, the authors could not find a significant
      correlation between tibiofemoral alignment and mean collagen diameter or
      percentage of collagen occupancy. The extent of tissue degeneration of the
      posterior cruciate ligament could not be predicted by clinical findings.
      Additional studies identifying the mechanical competency of the posterior
      cruciate ligament in osteoarthritis would be valuable.

PMID- 12072760
TI  - Increased expression of transforming growth factor-beta1 in patellar tendinosis.
AB  - Patellar tendinosis is characterized by longstanding localized and activity
      related pain, swelling and tenderness on palpation, and characteristic features
      on magnetic resonance imaging and ultrasonography and during surgical excision.
      Histologic examination of tendinosis tissues shows disrupted collagen matrix,
      increased cellularity, and increased proteoglycan stainability, but lack of
      inflammatory cell infiltration despite the clinical signs resembling
      inflammation. Disturbances in inflammatory response may be associated with the
      development of tendinosis. Expression of cyclooxygenase-2 and transforming growth
      factor-beta1 were detected in tendinosis, and the in vitro production of
      prostaglandin E2 by tendinosis and healthy tendon fibroblast cultures also was
      observed. Eleven patients with patellar tendinosis and 12 control subjects with
      healthy patellar tendons, but deficient anterior cruciate ligaments, were
      included in the current study. The percentages of immunopositive cells in
      tendinosis samples for cyclooxygenase-2 and transforming growth factor-beta1 were
      66.75 and 56.40, respectively, which were significantly higher than those of the
      control subjects (25.15 and 23.06 respectively). Tendinosis fibroblast culture
      also produced more prostaglandin E2 and active transforming growth factor-beta1.
      These findings indicate the involvement of prostaglandins and cytokines that may
      explain the clinical symptoms and nonhealing features of tendinosis.

PMID- 12072761
TI  - Does cryotherapy affect intraarticular temperature after knee arthroscopy?
AB  - Cryotherapy is a common modality used after arthroscopic procedures. The current
      authors investigated whether regions deeper than the lateral gutter experience
      similar temperature reductions with cryotherapy, supporting a more global
      temperature effect on the synovium. Thermocouple probes were arthroscopically
      placed intraarticularly in the medial gutter and suprapatellar pouch after
      routine knee arthroscopy. Twelve patients were divided into two groups for
      temperature measurement during 2 hours. Ice was applied only for the first hour
      in Group 1 (n = 6) and only for the second hour in Group 2 (n = 6). The medial
      gutter and suprapatellar pouch had significant decreases (average, 2.7 degrees -5
      degrees C) in the temperature when ice was applied and a significant increase
      (average, 1.7 degrees -3 degrees C) in the temperature without ice. Also, the
      temperatures in the medial gutter and suprapatellar pouch correlated with each
      other. At 1 hour, the mean difference between ice versus no ice was on average 6
      degrees C. Cryotherapy globally decreased intraarticular temperature in the
      absence of hemarthrosis.

PMID- 12072762
TI  - Treatment of acute Achilles tendon ruptures: a systematic overview and
      metaanalysis.
AB  - A quantitative systematic review of randomized and quasirandomized trials was
      conducted to determine the effect of surgical versus conservative treatment of
      acute Achilles tendon ruptures on rates of rerupture. Secondary outcomes included
      deep infection rates, return to normal function, and minor complaints. A search
      of computerized databases was conducted to locate clinical studies published from
      1969 to 2000. Additional studies were located through hand searches of major
      orthopaedic journals, bibliographies of major orthopaedic texts, and personal
      files. Of the 273 citations initially identified, 11 proved potentially eligible,
      and six met all eligibility criteria. Three investigators independently graded
      study quality and abstracted relevant data. Among the studies, surgical repair
      revealed a significant reduction in the risk of rerupture when compared with
      conservative treatment. Alternatively, the risk of infection with surgical repair
      was significantly increased. Pooled analysis of studies did not reveal any
      difference in the risk of minor complaints or return to normal function between
      surgical repair and conservatively treated groups. Surgical treatment
      significantly reduces the risk of Achilles tendon rerupture, but increases the
      risk of infection, when compared with conservative therapy. Wide confidence
      intervals around the estimates of risk reduction suggest a large trial is needed
      to establish risks and benefits.

PMID- 12072763
TI  - Giant-cell tumor of the appendicular skeleton.
AB  - The common objective of all surgical procedures in the treatment of giant-cell
      tumor of bone is to minimize the incidence of local recurrence. The purpose of
      this study was to determine what, if any, patient factors, tumor characteristics,
      or surgical practices correlate with local recurrence. Seventy-five patients
      treated for a giant-cell tumor of the appendicular skeleton were followed up for
      at least 2 years. The mean duration of followup was 62 months (range, 24-224
      months). The highest proportion of patients had intralesional curettage, high
      speed burring, and adjuvant treatment. Ten patients (13%) had a local recurrence.
      Bivariate analysis revealed that, with the numbers available, none of the patient
      variables, tumor variables, or surgical approaches correlated with local
      recurrence. Post hoc power analysis revealed the power of the study to be 33% to
      detect a clinically significant difference between treatment groups. The data
      presented here potentially could contribute to a metaanalysis, which would have
      the statistical power to determine which tumor-related factors and surgical
      techniques are most important in predicting recurrence in giant-cell tumor of
      bone.

PMID- 12072764
TI  - Malignant fibrous histiocytoma associated with diaphyseal medullary stenosis.
AB  - An unusual presentation of secondary malignant fibrous histiocytoma of the femur
      in a patient with diaphyseal medullary stenosis is described. The patient, a 42
      year-old man, presented with a painful lump in the right knee. A radiograph of
      the right femur showed lytic destruction. Characteristic features of longitudinal
      linear striations in the metaphysis and medullary stenosis in the diaphysis were
      observed in radiographs of the long tubular bones. A radiograph of the pelvis
      showed bilateral acetabular bone scleroses. After chemotherapy, surgical
      resection was done. On light microscopic examination, the tumor had features
      characteristic of malignant fibrous histiocytoma. Specimens from the diaphyseal
      medullary stenosis from the femur and tibia showed typical features of bone
      infarction. Radiographs of other members of the patient's family showed similar
      features of linear striation, cortical bone thickening, and acetabular sclerosis,
      including wavy, open growth plate of the iliac crest. The patient's aunt had died
      of a bone sarcoma in the shoulder region. It is important to recognize this
      extremely rare clinicopathologic type of diaphyseal medullary stenosis that
      frequently is associated with secondary high-grade sarcomas.

PMID- 12072765
TI  - Allograft arthrodesis treatment of bone tumors: a two-center study.
AB  - The current study consists of an outcome review of a consecutive series of 92
      patients with knee arthrodesis using an allograft, done for malignant or
      aggressive tumors in two centers on different continents during a period of 18
      years (mean followup, 5 +/- 4 years). The data were compiled by creating a
      computerized file using the information provided by both centers. Seventy-five of
      the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly
      osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the
      remaining 10 (11%) had benign disease, mostly giant cell tumor or revision
      procedures for failed allograft or total joint replacement. Seventy-two patients
      (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of
      the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16
      years; 51 were males and 41 were females. Tumor complications were a major
      problem for patients in the series. Thirty-four percent of the patients died, 47%
      had metastases develop, and 9% had a local recurrence. Allograft complications
      included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of
      44%. Repeat surgery was required for more than 50% of the patients with 26
      requiring one additional operation, 11 requiring two, and 10 requiring three or
      more operations. Nineteen of the patients required an amputation (20%), only four
      of which were for recurrent tumor. When these data were compared with data for a
      control series of 880 patients with allografts other than allograft arthrodeses,
      the complications were greater and the outcome less successful, suggesting that
      other approaches should be considered unless there are special indications for
      this procedure.

PMID- 12072766
TI  - Distal femur resection with endoprosthetic reconstruction: a long-term followup
      study.
AB  - The distal femur is a common site for primary and metastatic bone tumors and
      therefore, it is a frequent site in which limb-sparing surgery is done. Between
      1980 and 1998, the authors treated 110 consecutive patients who had distal femur
      resection and endoprosthetic reconstruction. There were 61 males and 49 females
      who ranged in age from 10 to 80 years. Diagnoses included 99 malignant tumors of
      bone, nine benign-aggressive lesions, and two nonneoplastic conditions that had
      caused massive bone loss and articular surface destruction. Reconstruction was
      done with 73 modular prostheses, 27 custom-made prostheses, and 10 expandable
      prostheses. Twenty-six gastrocnemius flaps were used for soft tissue
      reconstruction. All patients were followed up for a minimum of 2 years. Function
      was estimated to be good or excellent in 94 patients (85.4%), moderate in nine
      patients (8.2%), and poor in seven patients (6.4%). Complications included six
      deep wound infections (5.4%), six aseptic loosenings (5.4%), six prosthetic
      polyethylene component failures (5.4%), and local recurrence in five of 93
      patients (5.4%) who had a primary bone sarcoma. The limb salvage rate was 96%.
      Distal femur endoprosthetic reconstruction is a safe and reliable technique of
      functional limb sparing that provides good function and local tumor control in
      most patients.

PMID- 12072767
TI  - Biomechanical properties under cyclic loading of seven meniscus repair
      techniques.
AB  - The purpose of the current study was to obtain additional information about the
      biomechanical behavior of different fixation techniques for meniscus repair using
      recently developed biodegradable implants and suture repair techniques. The
      posterior horns of human menisci were used to investigate the meniscus repair
      construct of the Arrow, Screw, Stinger, Fastener, T-fix, and horizontal and
      vertical mattress suture. A 20 mm-longitudinal incision was made in the meniscus,
      similar to a bucket handle lesion, 3 mm from the meniscosynovial rim and was
      repaired. One hundred cycles between 5 N and 15 N were done using a tension load
      machine with a loading rate of 10 N/second. The stiffness, displacement, and
      pullout strength were examined. The significantly highest stiffness was found for
      the vertical mattress suture (17.1 N/mm) and Stinger (15 N/mm) followed by the
      Arrow (13.7 N/mm), T-fix (10.5 N/mm), and horizontal mattress suture (10 N/mm).
      Superior load to failure was obtained for the suture repair in comparison with
      the biodegradable implants. Despite the lower pullout strength of biodegradable
      implants, similar stiffnesses were found for the Stinger and Arrow in comparison
      with the mattress suture technique. These techniques provide the most rigid
      fixation that is essential for tissue healing.

PMID- 12072768
TI  - Patellar tendon fiber strains: their differential responses to quadriceps
      tension.
AB  - This study tested the hypothesis that the posterior fibers of the patellar tendon
      are subjected to higher tensile strains than the anterior fibers in response to
      quadriceps tension. The quadriceps tendon was loaded to 1 kN in 10 human cadaver
      knees and the tensile strain was measured in the anterior and posterior fibers of
      the patellar tendon. The central third patellar tendon was divided into anterior
      and posterior halves which were tensile tested to failure. The mean strain at 1
      kN load was 1.7% (90 degrees flexion), 2.7% (60 degrees ), and 3.9% (10 degrees )
      anteriorly, and 3.2% (90 degrees ) 4.6% (60 degrees ), and 4.9% (10 degrees )
      posteriorly. Quadriceps loading caused significantly greater strains in the
      posterior fascicles between 60 degrees and 90 degrees knee flexion. The material
      properties in the anterior and posterior regions were similar, except that
      failure strain was significantly higher posteriorly. Thus the posterior fascicles
      are adapted to sustain significantly greater tensile strains before failing. This
      suggests that the higher overall levels of tensile strain in the posterior fibers
      are not sufficient to explain the clinical pattern of patellar tendonitis.

PMID- 12072769
TI  - Tibial lesion in a 12-year-old boy.

PMID- 12072770
TI  - On the education of the orthopaedic resident.

PMID- 12072771
TI  - Longitudinal tibial fatigue fracture: an uncommon stress fracture with
      characteristic features.
AB  - PURPOSE: The author reports three cases of longitudinal tibial fatigue fractures,
      reviews the literature, and discusses characteristic features that suggest the
      diagnosis may be made by bone scintigraphy. METHODS: Radiographs and two- or
      three-phase bone scintigraphs with Tc-99m MDP were obtained in three runners who
      had exercise-related leg pain and whose clinical symptoms suggested either stress
      fractures or shin splints. The literature was reviewed and previously reported
      scintigraphic findings were compared with those seen in these three cases.
      RESULTS: In contrast to the focal, elliptical, cortex-based abnormal activity
      usually seen in the upper or middle tibia in patients with tibial stress
      fractures, all three patients had a long area of abnormal diffusely increased
      tibial activity that extended from the tibiotalar region proximally. This finding
      was seen on the 3-hour delayed static images of all three patients and was
      suggested on the blood-pool (tissue phase) images. The literature also contained
      reports of these same scan characteristics. Radiographs subsequently disclosed a
      longitudinal tibial stress fracture in one patient, computed tomography was
      positive in the second patient, and findings of clinical follow-up and
      radiographs were consistent with this diagnosis in the third patient. CONCLUSION:
      In the appropriate clinical setting and with normal or nondiagnostic radiographs,
      the presence of a long area of diffusely increased activity in the distal tibia
      extending proximally from the tibiotalar junction is indicative of a longitudinal
      fatigue fracture.

PMID- 12072772
TI  - The importance of renal localization with MIBG scintigraphy.
AB  - Although I-123 metaiodobenzylguanidine (MIBG) imaging is a well-validated
      technique for identification and evaluation of a pheochromocytoma, accurate
      interpretation can be confounded by tracer retention within the renal pelvis. The
      authors report two cases of abnormal MIBG accumulation in which renal
      localization was essential. In the first case, renal localization revealed uptake
      inferomedial to the left kidney in what was proved to be an extra-adrenal
      paraganglioma. In the second case, MIBG uptake in a similar location on the right
      was caused by uptake in the renal pelvis, a physiologic finding. When the
      location of MIBG uptake in the upper abdomen is uncertain, a renal scan should be
      obtained to exclude the possibility of radiolabeled MIBG tracer retention within
      the collecting system, a potential false-positive diagnosis of pheochromocytoma.

PMID- 12072773
TI  - Exercise renal scintigraphy shows renal ischemia in a transplanted kidney.
AB  - Exercise renography is essentially a research method to investigate hypertension
      and has very limited clinical application. Captopril renography has long been
      used to study renal artery stenosis causing hypertension with good results. The
      authors describe a patient with a transplanted kidney supplied by reversal of
      flow via the external iliac artery. A "steal phenomenon" of the kidney related to
      ambulation was considered likely. Ischemia of the transplanted kidney was
      revealed by exercise renography, which showed parenchymal trapping of radiotracer
      as a result of exercise.

PMID- 12072774
TI  - The bone scan flare phenomenon in non-small-cell lung cancer.
AB  - PURPOSE: The bone scan flare phenomenon, defined as an increase in the number or
      intensity of bone lesions with subsequent improvement while the patient is
      receiving chemotherapy, has been described in solid tumors including breast
      cancers and small-cell lung cancers. The purpose of this study was to verify the
      existence of the bone scintigraphic flare phenomenon in patients with non-small
      cell lung cancer (NSCLC) during chemotherapy and thus determine the utility of
      bone scintigraphy in the follow-up of these patients. MATERIALS AND METHODS:
      Thirty-three patients with NSCLC with bone metastases and who had been treated
      with chemotherapy were included in the study. The outcome of bone scintigraphy
      was compared with that in other neoplastic sites. RESULTS: The flare phenomenon
      was considered likely in 8 of the 33 patients. It was confirmed in two patients,
      invalidated in four, and remained doubtful in two. CONCLUSIONS: The bone flare
      phenomenon occurs in NSCLC. It renders bone scintigraphy less useful in the
      evaluation of tumoral response in the patients in whom it is considered likely.

PMID- 12072775
TI  - Comparison of radionuclide imaging and ultrasonography in the differentiation of
      acute testicular torsion and inflammatory testicular disease.
AB  - PURPOSE: Torsion of the testis is a urologic emergency that requires early
      diagnosis and prompt surgical treatment for testicular survival. However, the
      early differential diagnosis of acute testicular torsion from epididymitis or
      orchitis is often difficult. The aim of this retrospective study was to evaluate
      and compare the value of Tc-99m pertechnetate radionuclide imaging and
      ultrasonography in the differentiation of acute testicular torsion and
      inflammatory testicular diseases. METHODS: Twenty patients (age range, 5 to 38
      years) with possible acute testicular torsion from July 2000 to July 2001 were
      enrolled in this study. Ultrasonography was performed in all patients in the
      emergency room. Within 3 hours of ultrasonography, radionuclide imaging was also
      performed after intravenous injection of 5 to 15 mCi Tc-99m pertechnetate in the
      forearms. All of the patients with clinically suspected acute testicular torsion
      underwent surgery. The surgical findings and pathologic reports of these patients
      were reviewed and definite diagnoses were established. None of the other patients
      had surgery and were followed clinically for at least 1 month after
      ultrasonography and radionuclide imaging. RESULTS: Four patients with testicular
      torsion, 13 patients with inflammatory testicular disease, and three healthy
      persons had a final surgical and pathologic diagnosis or clinical follow-up, and
      all were accurately diagnosed by Tc-99m pertechnetate radionuclide imaging. In
      contrast, ultrasonography was less accurate in the diagnosis and differentiation
      of acute testicular torsion from inflammation. Only 1 of 4 patients with
      testicular torsion, 5 of 13 patients with inflammatory testicular disease, and 2
      of 3 healthy persons were diagnosed by ultrasonography. CONCLUSIONS: The results
      indicate that Tc-99m pertechnetate radionuclide imaging is a more useful and
      accurate imaging method than ultrasonography in the detection and differentiation
      of acute testicular torsion from inflammatory testicular disease in patients with
      acute scrotal pain.

PMID- 12072776
TI  - Pitfalls of radiation survey after brachytherapy implant removal preceding Tl-201
      study.
AB  - An unexpected elevated postimplant radiation survey is described in an elderly
      patient with an interstitial low-dose-rate iridium-192 (Ir-192) needle implant
      for endometrial cancer. The elevated activity was related to prolonged clearance
      of Tl-201 from a cardiac study that had been performed 7 days earlier. The Tl-201
      accumulated in the soft tissue, particularly the colon, resulting in increased
      survey readings over the abdomen and raising concern that an Ir-192 source
      remained within the patient. This case shows that delayed excretion of a
      diagnostic radionuclide agent can cause elevated activity high enough to confound
      postradiotherapy implant survey readings. The estimated surface exposure from a
      single iridium source left in the pelvis was determined using a phantom study.
      Possible factors causing decreased excretion of Tl-201 in a patient with heart
      disease, arteriosclerotic vascular disease, previous pelvic radiation therapy,
      and a brachytherapy procedure are discussed. A preloading radiation survey is
      recommended in patients who have had previous nuclear medicine studies involving
      radionuclides with long half-lives.

PMID- 12072777
TI  - Octreotide scans are positive in a subset of patients with hepatocellular
      carcinoma.
AB  - PURPOSE: In vitro data suggest that a proportion of hepatocellular carcinomas
      express the somatostatin receptor. However, in vivo data are lacking. There has
      been little reported use of octreotide scans in hepatocellular carcinomas. This
      study was performed to determine the percentage of positive results of octreotide
      scanning in patients with hepatocellular carcinoma. MATERIALS AND METHODS: In-111
      octreotide scans were performed in the standard manner in eight patients with
      unresectable hepatocellular carcinoma. Computer fusion imaging of the nuclear
      medicine and computed tomographic scans was performed in selected patients.
      RESULTS: Five of eight (63%) patients tested had hepatocellular carcinomas that
      displayed focal tracer uptake. CONCLUSIONS: This is the first report of positive
      uptake of octreotide scans in patients with hepatocellular carcinoma. These
      findings may have implications for the treatment of hepatocellular carcinoma with
      octreotide. Furthermore, these results may broaden the differential diagnosis in
      patients with positive results of octreotide scanning.

PMID- 12072778
TI  - Tc-99m sestamibi bone marrow scintigraphy in Gaucher disease.
AB  - PURPOSE: No imaging technique has been found to be adequate to assess the
      severity and extent of bone involvement in patients with Gaucher disease. Marrow
      involvement, as determined by Tc-99m sulfur colloid, correlated well with the
      clinical and radiologic changes of the skeleton, but a normal pattern was found
      in the early stages of the disease. Subsequently, Tc-99m sestamibi (MIBI) has
      been suggested for direct visualization of glycolipid deposits in the bone
      marrow. This study was initiated as a pilot using MIBI to detect various forms of
      bone disease in patients with Gaucher disease of varying severity. MATERIALS AND
      METHODS: Eleven patients (9 men; median age, 39.9; age range, 21 to 61 years)
      were evaluated. The clinical severity of disease was scored at presentation, and
      four patients with moderate to severe disease were treated with enzyme
      replacement therapy. Each patient underwent a radiographic skeletal survey, bone
      densitometry, and MIBI scintigraphy. The scan included static images of the lower
      limbs, with a whole-body scan acquired between the early and late acquisition.
      Tracer uptake in the bone marrow was graded and correlated with clinical and
      objective variables. RESULTS: All but one patient had increased MIBI uptake in
      the bone marrow. No correlation was noted between MIBI uptake and severity score,
      radiographic changes, densitometry z score, or treatment status. CONCLUSIONS:
      MIBI scanning is a sensitive technique for detecting bone marrow deposits in
      Gaucher disease, but it is inadequate for early identification of patients at
      high risk for skeletal complications or for the follow-up of patients treated
      with enzyme replacement.

PMID- 12072779
TI  - The diagnosis of coronary artery disease in hypertensive patients with chest pain
      and complete left bundle branch block: utility of adenosine Tc-99m tetrofosmin
      SPECT.
AB  - PURPOSE: Hypertensive patients with complete left bundle branch block who
      experience chest pain present special problems in the radionuclide diagnosis of
      coronary artery disease (CAD). The aim of this study was to assess the utility of
      Tc-99m tetrofosmin SPECT for the diagnosis of CAD in 35 hypertensive patients
      with left bundle branch block hospitalized for chest pain. MATERIALS AND METHODS:
      Images were analyzed semiquantitatively for the presence of both fixed or
      reversible perfusion defects (method A) or only reversible defects (method B) in
      the distribution of the left anterior descending artery (LAD) territory.
      Perfusion defects observed in the territory of any other coronary artery were
      always considered. Thirty-five patients without infarction underwent adenosine Tc
      99m tetrofosmin SPECT, transthoracic echocardiography, and coronary angiography.
      RESULTS: The mean left ventricular ejection fraction was calculated as 39.9% +/-
      11.6%, and the prevalence of CAD was 29%. The sensitivity of SPECT was identical
      for the two methods at 89%. The specificity increased 19% with method A and 54%
      with method B. The positive predictive value remained unsatisfactorily low with
      both methods (27% for method A and 40% for method B), and the negative predictive
      value improved from 83% with method A to 93% with method B. CONCLUSIONS: Only
      reversible perfusion defects in the LAD territory should be considered
      significant for CAD, and these patients should undergo coronary angiography.
      Reversible or fixed perfusion defects in the left circumflex and right coronary
      artery territories should be evaluated according to other clinical parameters
      (global left ventricular ejection fraction, extension of perfusion defects). The
      highly negative predictive value of adenosine SPECT could help in the exclusion
      of CAD.

PMID- 12072780
TI  - Adrenal hyperplasia in Cushing's syndrome demonstrated by FDG positron emission
      tomographic imaging.

PMID- 12072781
TI  - Another scintigraphic pattern of a postsurgical bile leak.

PMID- 12072783
TI  - Bleomycin-induced alveolitis detected by FDG positron emission tomography.

PMID- 12072782
TI  - Non-Hodgkin's lymphoma causing a symmetrical renal defect with the rim sign on
      bone scan.

PMID- 12072784
TI  - Neonatal gastric hemorrhage showing gallbladder visualization with tc-99m red
      blood cell scintigraphy.

PMID- 12072785
TI  - Imaging prostatitis with Tc-99m ciprofloxacin.

PMID- 12072786
TI  - Tc-99m MIBI SPECT in a patient with congenitally corrected transposition of the
      great arteries and situs solitus.

PMID- 12072787
TI  - Preserved value of bone scintigraphy for the detection of skeletal metastases in
      prostate cancer patients with low prostate-specific antigen levels: effect of
      hormonal therapy and poor histologic differentiation.

PMID- 12072788
TI  - False-positive Ga-67 citrate scan secondary to an inguinal hernia.

PMID- 12072789
TI  - Asymmetric FDG uptake in a lactating breast.

PMID- 12072790
TI  - Monostotic Paget's Disease of a cervical vertebra: differential diagnosis with F
      18 FDG positron emission tomography using a coincidence technique and with Tc-99m
      dicarboxypropane diphosphonate.

PMID- 12072792
TI  - Hemifacial microsomia, external auditory canal atresia, deafness and Mullerian
      anomalies associated with acro-osteolysis: a new autosomal recessive syndrome?
AB  - We report the combination of hemifacial microsomia, external auditory canal
      atresia, deafness and acro-osteolysis in several members of a highly
      consanguineous Asian family. In addition Mullerian anomalies have been found in
      two female members of the family. The external auditory canal stenosis and
      Mullerian anomalies in this family are similar to those reported by Winter et al.
      [(1968) J Pediatr 72 : 88-93] and overlap with those found in Goldenhar syndrome
      and Mullerian duct/renal aplasia/cervicothoracic somite dysplasia (MURCS), CHARGE
      and VATER associations. However, to the authors' knowledge, acro-osteolysis has
      not been reported in patients with any of these conditions. Overall, the findings
      in this family appear to be unique and the presence of consanguinity suggests an
      autosomal recessive condition with variable expression.

PMID- 12072791
TI  - Demonstration of skeletal tuberculosis with Tc-99m (V) DMSA scintigraphy and a
      negative Ga-67 scan.

PMID- 12072793
TI  - Tibial agenesis with radial ray and cardiovascular defects.
AB  - The combination of tibial agenesis with radial ray and cardiovascular defects has
      been observed in patients with Mendelian disorders and in those with multiple
      congenital anomalies of unknown cause. We report two apparently unrelated
      children who had unusual combinations of such findings in association with other,
      predominantly midline, anomalies (imperforate anus, extra ribs, uterus
      didelphys). Comparison of the anomalies in these infants and similar cases from
      the literature suggests that they may represent examples of an association of the
      cardiogenic and limb developmental fields occurring either as manifestations of a
      previously unrecognized single gene disorder or as an expansion of the VACTERL
      association.

PMID- 12072794
TI  - Twenty-nail dystrophy in a mother and her 7-year-old daughter associated with
      balanced translocation 46, XX, t(6q13;10p13).
AB  - Twenty-nail dystrophy (TND) is an autosomal dominantly inherited idiopathic nail
      dystrophy characterized by excessive longitudinal striations and numerous
      superficial pits on nails with a typical 'sand papered' rough appearance. It is
      evident at birth and progresses slowly. It can also be associated with various
      diseases including lichen planus, alopecia areata, eczema, vitiligo and
      psoriasis. Peripheral blood chromosome analysis has not been performed in
      previously reported cases of TND. We report a mother and her 7-year-old daughter
      with TND. Both of them had a balanced translocation 46, XX, t(6q13;10p13). This
      may be a coincidental finding or may be related to the gene locus of TND.

PMID- 12072795
TI  - Hypohidrotic ectodermal dysplasia with tibial aplasia.
AB  - We report an inbred Tunisian family, in which 19 members had an ectodermal
      syndrome involving the teeth, hair, nails and skin. Ectrodactyly occurred as an
      isolated manifestation in one, and with tibial aplasia in two others. None had
      facial clefts. Dysplastic ears were part of the syndrome.

PMID- 12072796
TI  - A severe case of oculo-ectodermal syndrome?
AB  - We describe a child with features of the oculo-ectodermal syndrome, who in
      addition to the cardinal manifestations of cutis aplasia and epibulbar dermoid
      had a number of other features. These include laryngomalacia, an anterior anus,
      microcephaly and significant developmental delay. The parents are of New Zealand
      Maori ancestry and are related as half first cousins, raising the possibility
      that this syndrome may be recessively inherited.

PMID- 12072797
TI  - Evidence for autosomal recessive inheritance of split hand/split foot
      malformation: a report of nine cases.
AB  - Split hand and foot malformation syndrome (SHFM) is characterized by the absence
      of the central digital rays, deep median cleft, and syndactyly of the remaining
      digits. The majority of the familial cases are inherited in an autosomal dominant
      manner. Here we report on nine cases of SHFM in an inbred kindred. A variable
      intrafamilial expression of the malformation pattern is apparent. Autosomal
      recessive inheritance and a two-locus model are discussed.

PMID- 12072798
TI  - Microgastria-limb reduction anomaly with total amelia.
AB  - The Microgastria-limb reduction anomaly is a rare disorder of unknown aetiology
      in which microgastria is associated with limb defects, along with splenic and
      other variable congenital abnormalities. In 15 previously reported cases, none
      have had the most extreme form of amelia. We report the clinical progress of a 3
      year-old girl with severe microgastria and total amelia who has been managed
      conservatively with minimal surgical intervention.

PMID- 12072799
TI  - A second family with blepharo-naso-facial syndrome.
AB  - We report a mother and son with expressionless facies, thickened facial skin,
      telecanthus with blepharophimosis, lacrimal duct anomalies, unusual nasal shape,
      and mild excess interdigital webbing. The only other family known to exhibit this
      constellation of features was reported by Pashayan and colleagues 23 years ago [
      Pashayan et al. (1973) Am J Dis Child 125:389--393]. The similarity between these
      two families and a kindred described by Sommer, in which a PAX3 mutation has been
      defined, suggests that a developmental gene abnormality might be the cause of the
      blepharo-naso-facial syndrome. To date, studies of PAX3 have failed to reveal a
      mutation.

PMID- 12072800
TI  - A variant of Fine-Lubinsky syndrome: a Japanese boy with profound deafness,
      cataracts, mental retardation, and brachycephaly without craniosynostosis.
AB  - A Japanese boy with a hearing deficit, cataracts, mental retardation, and
      brachycephaly without craniosynostosis is described. We believe that this patient
      represents a variant of the Fine-Lubinsky syndrome, and is the first report from
      a racial group other than Caucasian.

PMID- 12072801
TI  - Atypical macrocephaly-cutis marmorata telangiectatica congenita with
      retinoblastoma.
AB  - We describe a boy presenting with macrosomy, body asymmetry, cutis marmorata and
      tall stature who developed a retinoblastoma. Although he does not have
      macrocephaly, his clinical picture is compatible with the diagnosis of
      Macrocephaly-cutis marmorata telangiectatica congenita syndrome (M-CMTC).
      Interestingly, retinoblastoma is not generally associated with overgrowth
      syndromes, and its occurrence in this patient suggests that M-CMTC is also a
      tumour-prone syndrome.

PMID- 12072802
TI  - Lethal non-rhizomelic dysplasia epiphysealis punctata.
AB  - We describe two new cases of a rare form of lethal chondrodysplasia punctata (so
      called X-linked dominant, non-rhizomelic form), a condition characterized by
      widespread multicentric stippled calcifications of the cartilaginous parts of the
      long bones, spine, ribs and flat bones. The mother of one of the patients had
      bone dysplasia consistent with the X-linked dominant form of chondrodysplasia
      punctata. We suggest that a skeletal survey, including lateral view of the spine,
      together with biochemical studies of peroxisomal status are indicated in all
      newborns with severe, unusual forms of chondrodysplasia punctata. In this way,
      accurate categorization of the lethal, non-rhizomelic types of this condition
      will be facilitated.

PMID- 12072803
TI  - Tourette syndrome, growth retardation, and platyspondyly: an entity?
AB  - A 14-year-old male is described with Tourette syndrome, platyspondyly, a marked
      delay in bone age, growth retardation that is more expressed in the limbs and
      talipes equinovarus. This appears to be a new entity.

PMID- 12072804
TI  - Hepatic dislocation associated with left-sided congenital diaphragmatic
      eventration without situs inversus.
AB  - A 3-month-old boy with hepatic dislocation and left-sided congenital
      diaphragmatic eventration without situs inversus is described. From a review of
      the literature this appears to be a new clinical condition which may be termed
      incomplete heterotaxy of abdominal viscera.

PMID- 12072806
TI  - Proboscis lateralis: a case report.

PMID- 12072805
TI  - Cenani-Lenz syndrome: report of a new case and review of the literature.
AB  - A female child with Cenani-Lenz syndrome is described and the literature on this
      syndrome is reviewed.

PMID- 12072808
TI  - Dandy-Walker malformation in Rubinstein-Taybi syndrome: a rare association.
AB  - A female infant is described with the rare association of Dandy-Walker
      malformation in Rubinstein-Taybi syndrome.

PMID- 12072807
TI  - Sacral appendage associated with a mutation in FGFR2.
AB  - We report a baby with craniosynostosis and a sacral appendage who has been found
      to have a Ser351Cys mutation in the fibroblast growth factor receptor 2 gene
      (FGFR2). This is the first report of sacral appendage associated with a confirmed
      mutation in one of the FGFR genes, and adds to the spectrum of abnormalities
      which can be seen in patients with FGFR mutations.

PMID- 12072809
TI  - Cyclopia-astomia-agnathia-holoprosencephaly association: a case report.
AB  - A female infant is described with cyclopia-astomia-agnathia-holoprosencephaly
      association. The authors discuss whether the use of salicylates in early
      pregnancy is implicated.

PMID- 12072810
TI  - Concordance as well as discordance for congenital malformations in valproate
      exposed half-siblings with parental consanguinity may indicate a specific gene
      teratogen interaction.
AB  - The possibility of gene-teratogen interaction is suggested in a family formerly
      reported by Gardner et al. [(2001) Clin Dysmorphol 10:203-208] in which both
      concordance and discordance exist for congenital malformations in equally
      valproate-exposed siblings.

PMID- 12072812
TI  - Spitz nevus and its histologic simulators.
AB  - Spitz nevi continue to pose a considerable diagnostic challenge to the
      histopathologist. Key features of Spitz nevus and its variants are discussed and
      contrasted with the telltale signs of malignancy of "Spitzoid" melanomas. The
      importance of the histologic features of the deep, rather than superficial, part
      of the lesions is emphasized.

PMID- 12072813
TI  - An approach to the diagnosis of flat intraepithelial lesions of the urinary
      bladder using the World Health Organization/ International Society of Urological
      Pathology consensus classification system.
AB  - The classification of flat urothelial (transitional cell) lesions with atypia has
      historically varied in its application from institution to institution with no
      fewer than six major nomenclature systems proposed in the past 25 years. In 1998,
      the World Health Organization/ International Society of Urological Pathology
      (WHO/ISUP) published a consensus classification that included the following
      categories for flat urinary bladder lesions: reactive atypia, atypia of unknown
      significance, dysplasia (low-grade intraepithelial neoplasia), and carcinoma in
      situ (high-grade intraepithelial neoplasia). This classification expands the
      definition traditionally used for urothelial carcinoma in situ, basing its
      diagnosis primarily on the severity of cytologic changes. In proposing the
      classification system for flat lesions of the bladder with atypia, it was hoped
      that consistent use of uniform diagnostic terminology would ultimately aid in a
      better understanding of the biology of these lesions. In this review, the authors
      discuss the history of the concept of flat urothelial neoplasia, the rationale
      and histologic criteria for the WHO/ISUP diagnostic categories, an approach to
      the diagnosis of flat lesions, and problems and pitfalls associated with their
      recognition in routine surgical pathology specimens.

PMID- 12072814
TI  - Intraoperative evaluation of sentinel lymph nodes for breast carcinoma: current
      methodologies.
AB  - Sentinel lymph node biopsy is an important new addition to the surgical
      management of patients with breast carcinoma. Sentinel nodes have a higher chance
      of containing metastases than do nonsentinel nodes. Sentinel lymph node biopsy
      provides an opportunity to stage breast carcinoma patients more accurately and to
      modify subsequent treatment. One of the most exciting current roles of sentinel
      lymph node biopsy is the ability to stage patients intraoperatively, allowing a
      one-step axillary lymph node dissection if the sentinel lymph node contains
      metastatic carcinoma. Currently, intraoperative evaluation of sentinel lymph
      nodes is performed using imprint cytology with or without rapid cytokeratin
      staining, frozen sectioning with or without rapid cytokeratin staining, scrape
      preparations, or some combination of these techniques. We review the relative
      strengths and weaknesses of these different methodologies. A great deal of
      controversy exists regarding the management of patients with metastatic breast
      carcinoma, particularly those patients with occult and micrometastatic disease.
      These issues are beyond the scope of this article.

PMID- 12072815
TI  - Autoimmune cholangitis: not just AMA-negative primary biliary cirrhosis.
AB  - Variant forms of chronic cholestatic liver disease in adults, such as autoimmune
      cholangitis, primary biliary cirrhosis-autoimmune hepatitis overlap, and primary
      sclerosing cholangitis-autoimmune hepatitis overlap constitute approximately 20%
      of cases of autoimmune liver disease. Retrospective study design may obscure
      subtle differences in clinical features. Careful prospective studies are needed
      to help clarify classification of these disorders. Autoimmune cholangitis is
      often considered synonymous with antimitochondrial antibody-negative primary
      biliary cirrhosis, but may instead be a heterogeneous group of disorders
      including some cases of isolated small duct primary sclerosing cholangitis. The
      variable response of variant syndromes to established therapies such as
      corticosteroids provides justification for continued efforts to define their
      clinicopathologic features.

PMID- 12072816
TI  - Salivary gland hyperplasia.
AB  - Thirteen cases of adenomatous ductal hyperplasia (ADH) of the major salivary
      glands coexisting with salivary gland tumors or chronic parotitis are reported.
      The proliferating ducts have the morphology and immunohistochemistry similar to
      intercalated duct epithelium. Adenomatous ductal hyperplasia is compared to
      adenomatoid acinar hyperplasia (AAH), a lesion found predominantly in intraoral
      salivary glands and histologically composed of hyperplastic acinar cells. The
      exact nature of both lesions is not clear. However, ADH may be a precursor lesion
      of salivary gland tumors (especially epithelial-myoepithelial carcinomas),
      whereas AAH may represent a reactive process of idiopathic nature.

PMID- 12072817
TI  - Atypical polypoid adenomyoma.

PMID- 12072820
TI  - Transcripts, transcripts, everywhere.

PMID- 12072821
TI  - [Non invasive investigation of muscle diseases using 31P magnetic resonance
      spectroscopy: potential in clinical applications].
AB  - P-31 MRS has become in a very short time, a major new tool to explore muscle
      metabolism for clinical diagnostic purposes, while offering a unique non-invasive
      way to conduct advanced basic research in muscle physiopathology. The comparative
      analysis of normal and diseased muscle remains a major requirement to further
      define metabolic events surrounding muscle contraction and the metabolic
      anomalies underlying pathologies. Also, standardized rest-exercise-recovery
      protocols for exploration of muscle metabolism by P-31 MRS in healthy volunteers
      as well as in patients with intolerance to exercise need to be developed. Our
      protocol is based on a short term intense exercise which is very informative and
      well accepted by volunteers and patients. Invariant metabolic parameters have
      been defined to characterize the normal metabolic response to the protocol.
      Deviations from normality can be directly interpreted in terms of specific
      pathologies in some favorable cases. In most cases, P-31 MRS provides valuable
      information which has to be processed in conjunction with traditional invasive
      biochemical, electrophysiological and histoenzymological tests. For malignant and
      exercise hyperthermias, P-31 MRS constitutes a diagnostic tool with 100p.cent
      sensitivity, as compared to contracture tests on muscle biopsies. P-31 MRS has
      proved particularly useful in the therapeutic follow-up of palliative therapies
      (coenzyme Q treatment of mitochondriopathies) and in family investigations. It is
      now an accepted diagnostic tool in the array of tests which are used to
      characterize muscle disorders in clinical routine. As a research tool, it will
      keep bringing new information on the physiopathology of muscle diseases in animal
      models and in humans and should play a role in the metabolic characterization of
      gene therapy.

PMID- 12072823
TI  - [Dysfunction of the magnocellular pathway in Alzheimer's disease].
AB  - Visual disturbances are a common feature of Alhzeimer's disease. They are related
      primarily to visuo-spatial deficits. The pathways mediating visuo-spatial and
      form identification are at least partially segregated in the brain. The
      magnocellular pathway has characteristics which make it more suitable for
      detecting dynamic form, motion and depth. We assessed by means of psychophysical
      and electrophysiological testings the properties of the parvo and the
      magnocellular pathways. We found contrast sensitivity deficits for the low and
      middle spatial frequencies, a significant reduction of the amplitude of the
      steady-state pattern VEP's at 16, 20 and 24 Hz, abnormal transient pattern VEP's
      only for the major positivity (P100) and abnormal flash VEP's (delayed P2) as
      previously observed. The temporal frequency deficits and other abnormalities
      pointed out in this study, could be related to a dysfunction of the M-pathways in
      Alzheimer's disease.

PMID- 12072822
TI  - [Thrombophilias associated with cerebral venous thrombosis].
AB  - Many coagulation disorders have been associated with cerebral venous thrombosis.
      These disorders may be primary like protein C and S deficiency, antithrombine III
      deficiency and activated protein C resistance. Antiphospholipid antibodies
      represent an acquired disorders of coagulation. A prothrombotic state induced by
      more common factor including oral contraceptive, pregnancy and puerperium
      increases the venous thrombosis risk.

PMID- 12072824
TI  - [Sub-cortico-frontal encephalopathy and choreic movements related to recombinant
      interferon-alpha 2b].
AB  - Interferon (IFN)-alpha is associated with central nervous system (CNS) side
      effects such as depression and suicide ideation, somnolence, confusion,
      drowsiness, psychomotor slowing, memory impairment and visual disorientation.
      More severe complications are uncommon and include frank paranoia, dementia,
      coma, seizures and neuropathy. With the increasing long-term and extensive use of
      interferon (IFN)-alpha several new neurologic adverse effects have been
      recognized. We report on two patients who developed severe subcortico-frontal
      impairment, associated in one case with choreic movements, after a long-term
      treatment with IFN-alpha 2b for hematologic malignancies. Our patients rapidly
      and completely recovered from their cognitive and motor symptoms after the
      discontinuation of the drug. The same neurologic symptoms reappeared when we
      attempted to reintroduce lower doses of IFN-alpha in one case. Although little is
      known regarding IFN-alpha actions in the CNS, several possible mechanisms may
      underlie its neurotoxicity and might result from complex direct and indirect
      effects involving brain vasculature, neuroendocrine system, neurotoxic secondary
      cytokines'release and neurotransmitters.

PMID- 12072825
TI  - [Nocturnal oxymetry in patients with amyotrophic lateral sclerosis: role in
      predicting survival].
AB  - Death is the most important end point along the course of amyotrophic lateral
      sclerosis (ALS). It is commonly attributed to a respiratory failure in relation
      with a restrictive respiratory disorder. However, in clinical practice, it is
      frequent to observe that death has not direct relation with the values of the
      respiratory function, at least measured with vital capacity. It is also frequent
      that relatives report sudden death during nocturnal sleep. All these features
      raised the question of the possible relation between death and nocturnal oxymetry
      in ALS patients. In a prospective study, we studied 69 ALS patients. We recorded
      demographic data, clinical parameters as manual muscle testing and functional
      scales, various parameters of oxymetry measured by pulse oxymetry recorded during
      night, slow vital capacity and survival time. There is a strong correlation
      between survival time measured by Kaplan Meier curves and log rank and the mean
      nocturnal saturation. We determined 93 mmHg as a threshold value. Below this
      threshold, mean survival time was 7.5+/-1.6 months and above it was equal to
      18.5+/-1.5; relative risk was 3.31. These data confirm the importance of
      nocturnal oxymetry on survival in ALS patients both in clinical practice and in
      view of therapeutic trials.

PMID- 12072827
TI  - [Incidence of constipation after recent vascular hemiplegia: a prospective cohort
      of 152 patients].
AB  - Constipation is a major problem for institutionalized patients. This prospective
      study was performed on a population of 152 in-patients of a stroke rehabilitation
      center. Constipation was defined as less than three stools weekly or the use of
      laxative medication. Constipation occurred in sixty percent of the patients. The
      incidence of constipation was not related to age or sex but was strongly related
      to functional status of patients assessed by Barthel Index (p<0.003). The
      influence of both brain lesion or reduce activity is evaluated.

PMID- 12072826
TI  - [Hereditary neuropathy with liability to pressure palsies: study of six Spanish
      families].
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant inherited demyelinating neuropathy typically characterized by recurrent
      episodes of acute painless peripheral nerve palsies often preceded by minor
      trauma or compression at entrapment sites. However, less classical phenotypes
      have been reported. A 1.5 Mb deletion in chromosome 17 p11.2 has been shown to be
      the genetic basis of the disease in the majority of HNPP patients. The few
      families without this deletion harbored a mutation in the PMP22 gene. We
      performed a clinical, neurophysiological and molecular genetic study of 6 Spanish
      HNPP families. Five families (22 individuals) showed the classical chromosome 17
      p11.2 deletion and one family (3 individuals) had a novel 3'splice-site mutation
      in PMP22. Neurophysiological abnormalities were detected in all symptomatic
      (n=21) and asymptomatic (n=4) deletion or mutation carriers, even in childhood.
      In addition to the typical presentation we observed other phenotypes: recurrent
      focal short-term sensory symptoms, a progressive mononeuropathy, a Charcot-Marie
      Tooth (CMT) disease-like chronic progressive polyneuropathy, a chronic sensory
      polyneuropathy and a chronic inflammatory demyelinating polyneuropathy. We report
      new or very rare phenotypesThese atypical clinical aspects and intrafamilial
      heterogeneity are present in families with the HNPP deletion as well as in the
      family with the PMP22 mutation. However, the CMT disease-like chronic
      polyneuropathy was more common in the PMP22 mutation family. Intrafamilial
      heterogeneity also seemed to be more pronounced in this kinship. Patients in this
      family had a mild chronic motor and sensory polyneuropathy neurophysiologically
      characterized by delayed distal latencies, reduced nerve conduction velocities
      (NCV) within the demyelinating range, mildly decreased amplitudes of motor and
      sensory evoked potentials and absence of conduction blocks. In contrast, patients
      with the common HNPP deletion, regardless of their phenotype, had a diffuse
      increase in distal motor latencies contrasting with moderately reduced motor
      NCVs, preserved sensory nerve action potentials, slowing of NCVs at the common
      entrapment sites and occasionally conduction blocks. In this study we confirm the
      clinical and molecular heterogeneity of HNPP, emphasizing the need for a mutation
      analysis of the PMP22 gene when the common 17p11.2 deletion is not found in
      clinically suspected HNPP patients. We conclude that the 3'splice-site mutation
      in PMP22 and the common HNPP deletion have largely the same functional
      consequences although some clinical and neurophysiological differences were
      observed.

PMID- 12072828
TI  - [SPECT-identified hypoperfusion of the left temporomesial structures in a Kleine
      Levin syndrome].
AB  - A 13-year-old boy developed typical features of Kleine-Levin syndrome. Routine
      investigations and MRI were normal. SPECT, performed both during an attack and
      during a symptom-fee period, demonstrated clear hypoperfusion of the left
      mesiotemporal structures. The possible implications of this finding are
      discussed.

PMID- 12072829
TI  - [Vertebro-basilar ischemic strokes and aseptic meningitis, late complications of
      Fabry's disease].
AB  - Fabry's disease, also called angiokeratoma corporis diffusum universal, is a rare
      cause of stroke in the young. We report the case of a 39-year-old man who
      presented with relapsing vertebro-basilar ischemic strokes. Biological tests
      showed the presence of an aseptic meningitis and a biological inflammatory
      syndrome, suggesting a particularly progressive illness. The possible mechanisms
      involved in this exceptional association are discussed.

PMID- 12072830
TI  - [Pulsating exophtalmos and contralateral carotid-cavernous fistula].
AB  - A rare case of spontaneous carotid-cavernous fistula with contralateral clinical
      signs (ocular discomfort, pulsating exophthalmos, chemosis, ptosis) is reported.
      It was associated with partial thrombosis of the ipsilateral cavernous sinus. It
      was cured with conservative treatment after six months. Anatomical knowledge of
      the cavernous sinus remains essential for better understanding of this original
      clinical presentation.

PMID- 12072831
TI  - [Stiff limb syndrome associated with Hashimoto's encephalopathy: improvement
      after corticotherapy].
AB  - Stiff limb syndrome is a recently described variant of stiff man syndrome and is
      characterized by limb stiffness and spasms. Unlike stiff man syndrome, stiff limb
      syndrome is rarely associated with anti GAD antibodies, poorly improves after
      symptomatic treatment, and has a relapsing and remitting course. Both stiff man
      and stiff limb syndromes are frequently associated with auto-immune diseases. We
      report a case of a 70-year old man who presented with a stiff limb syndrome
      associated with symptoms highly suggestive of Hashimoto's encephalopathy. The
      signs of encephalopathy dramatically resolved after corticosteroid treatment, and
      remissions was complete after 12 months. The stiff limb syndrome had a remitting
      course despite symptomatic treatment including diazepam, baclofen and vigabatrin
      and immunomodulating treatments including corticoid and intravenous
      immunoglobulins.

PMID- 12072832
TI  - [Slow channel syndrome due to an autosomal translocation at 2q31-9p27].
AB  - A 27-year-old man complained of cervicoscapular and forearm weakness and
      amyotrophy. Electromyographic evaluation showed neuromuscular transmission
      dysfunction and a repetitive compound muscle action potential to a single
      stimulus. Prostigmine did not improve neuromuscular transmission. The genetic
      analysis of the patient's lymphocytes demonstrated a chromosomic 2q31-9p27
      translocation. The combination of the clinical and electrophysiological data as
      well as the lack of auto-immunity signs against neuromuscular junction
      constituents led to the diagnosis to congenital postsynaptic myasthenic syndrome
      also called slow channel syndrome. This congenital myasthenic syndrome is for the
      first time associated with an autosomal translocation 2q31-9p27.

PMID- 12072835
TI  - [Acute motor axon neuropathy, subtype of Guillain-Barre syndrome].

PMID- 12072836
TI  - [MRI findings in pituitary apoplexy].

PMID- 12072837
TI  - [Rush dyskinesia scale or Goetz scale].

PMID- 12072838
TI  - Human cytomegalovirus infection and abortion: an immunohistochemical study.
AB  - BACKGROUND: Cytomegalovirus (HCMV) has been described in abortion tissues, but
      seldom associated with inclusion bodies. However, the possible pathogenic role of
      this virus in abortion is under discussion. We attempted to verify the
      relationship between HCMV antigens in tissues from first trimester abortions
      presenting with inflammatory lesions. MATERIAL/METHODS: Sixteen cases of first
      trimester abortions with inflammatory lesions were selected from 340 cases
      studied at the Pathology Unit of the University Hospital in Vit ria, Esp rito
      Santo State, Brazil. Paraffin-embedded sections were subjected to indirect
      immunofluorescence (IFI) and immunoperoxidase (PAP), using monoclonal antibodies
      directed against immediate early (IEA) and late antigens (LA) of HCMV. RESULTS:
      Twelve out of sixteen cases (75%) presented at least one HCMV antigen. Eight
      cases presented both antigens, three cases only the IEA and one case only the LA.
      These antigens were present in decidual cells, in stromal cells of chorionic
      villi and in trophoblastic cells. CONCLUSIONS: The results showed high frequency
      of HCMV antigens in tissues from first trimester abortion. This frequency, higher
      than that previously reported, was probably due to the fact that necro
      inflammatory lesions were always present in selected cases. The presence of LA in
      trophoblastic cells is evidence for cell permissiveness to viral replication in
      vivo. The results showing high presence of HCMV antigens in tissues from abortion
      with inflammatory lesions suggest a possible relationship of HCMV infection with
      inflammation and pregnancy loss.

PMID- 12072839
TI  - Technologies and methods in nuclear medicine.

PMID- 12072841
TI  - Collimators.
AB  - In this article the present knowledge of the collimators used for single photon
      imaging in Nuclear Medicine is recapped. In the introduction, the classic
      formulas to describe the performances of multihole collimator are presented with
      an overview of the basic concepts. In the subsequent sections, the tools
      available for the characterization of multihole collimators are described. The
      characterization is divided into aspects related to the geometrical response and
      aspects related to effects due to interaction of photons with the collimator.
      Nowadays a rather complete theoretical description of the collimator geometrical
      response is available. In section Collimator characterization: theory a general
      formulation that is valid for a wide range of collimators is outlined. In section
      Collimator characterization: numerical methods the kind of knowledge that can be
      derived today from numerical computing methods about the penetration and scatter
      effects is presented. The problem of performances optimization in collimator
      design is described in section Collimator design. Difficulties and some new
      perspectives on avoiding both penetration and hole pattern artifacts while
      designing high-energy collimators are mentioned.

PMID- 12072842
TI  - Design considerations for PET scanners.
AB  - In 2-D PET scanners employing septa, scattered radiation is reduced by the septa,
      placing less importance on good energy resolution. Additionally, the reduced
      sensitivity in 2-D limits the maximum countrates encountered in clinical FDG
      studies. In contrast, 3-D PET scanners rely on good energy resolution to reduce
      the scattered radiation and also must deal with countrates, which are typically 5
      times higher than in 2-D mode. To achieve good energy resolution, 3 factors must
      be considered: 1) choice of a scintillator with good intrinsic energy resolution,
      2) choice of a crystal dimension which transmits a uniform amount of light to the
      PMT in order to avoid light loss along the length of the crystal and 3) choice of
      a crystal-to-PMT coupling which collects a uniform amount of light from all
      crystals. As PET scanners are being designed using new, faster scintillators for
      3-D imaging, the appropriate trade-off between energy resolution and countrate
      capability must be found to give the best overall system performance. An example
      of a fully 3-D PET scanner is the Allegro (ADAC Laboratories), which uses GSO as
      the detector material. Given the right choice of material and design parameters,
      good quality, high contrast images can be obtained in 3-D in a relatively short
      time.

PMID- 12072840
TI  - Solid state detectors in nuclear medicine.
AB  - Since Nuclear Medicine diagnostic applications are growing fast, room temperature
      semiconductor detectors such CdTe and CdZnTe either in the form of single
      detectors or as segmented monolithic detectors have been investigated aiming to
      replace the NaI scintillator. These detectors have inherently better energy
      resolution that scintillators coupled to photodiodes or photomultiplier tubes
      leading to compact imaging systems with higher spatial resolution and enhanced
      contrast. Advantages and disadvantages of CdTe and CdZnTe detectors in imaging
      systems are discussed and efforts to develop semiconductor-based planar and
      tomographic cameras as well as nuclear probes are presented.

PMID- 12072843
TI  - Dual-modality PET/CT tomography for clinical oncology.
AB  - Diagnosis and follow-up in clinical oncology are traditionally based on computed
      tomography (CT). In recent years, however, functional imaging using positron
      emission tomography (PET) has been recognized as an important imaging modality
      and adjunct to CT that provides complementary metabolic information in many
      oncology applications. To overcome the challenges of aligning independently
      acquired PET and CT image sets several ad hoc concepts of integrating PET and CT
      imaging in a single device have been proposed. This article comments on the
      development of the first combined dual-modality PET/CT prototype at the
      University of Pittsburgh, and illustrates commercial advances to dual-modality
      PET/CT tomography. The current PET/CT designs from the major manufacturers
      comprise a commercial CT scanner in tandem with a commercial PET scanner. While
      the level of physical integration is actually less than that of the original
      prototype it is fair to assume that current PET/CT models may serve as
      intermediate solutions towards near-future design concepts that aim at greatly
      reduced costs of the dual-modality tomographs and offer a greater level of
      physical integration. The goal of the next generation of PET/CT systems is to
      design and build a device specifically for imaging the function and anatomy of
      cancer in the most informative and effective way without necessarily
      conceptualizing it as combined PET and CT scanners. Such a concept of a
      diagnostic imaging device relates more to a disease management approach rather
      than the usual division into medical specialities such as radiology and nuclear
      medicine.

PMID- 12072844
TI  - Advances in animal PET scanners.
AB  - Nowadays, a growing number of research groups shows a great interest for the
      application of PET and SPECT techniques to the development of new drugs.
      Preliminary studies on small animals require high performance dedicated scanners
      with a higher spatial resolution and sensitivity than those of clinical systems.
      In this paper the potential applications of such innovative instruments are shown
      together with a brief review of the dedicated PET and SPECT tomographs developed
      worldwide. Most of the scanners have been built as research prototypes. Only two
      are commercially available: micro-PET(R), designed and developed at UCLA, Los
      Angeles as a research prototype, and now produced and distributed by Concorde
      Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd.
      (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform
      both PET and SPECT studies, has been developed at the University of Ferrara. The
      technical characteristics and performance of this scanner are described.
      Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now
      under study in various international research centers. The advantages of this new
      generation of animal scanners will be briefly outlined.

PMID- 12072845
TI  - Monte Carlo simulations in SPET and PET.
AB  - Monte Carlo methods are extensively used in Nuclear Medicine to tackle a variety
      of problems that are difficult to study by an experimental or analytical
      approach. A review of the most recent tools allowing application of Monte Carlo
      methods in single photon emission tomography (SPET) and positron emission
      tomography (PET) is presented. To help potential Monte Carlo users choose a code,
      we present advantages and disadvantages of the different types of Monte Carlo
      codes currently available for SPET and PET, discuss common and specific features
      of the codes, classify the codes with respect to these features, comment key
      properties for a code to be appropriate for a given purpose and, at last, we
      consider the possibility of going towards a standardisation of the description of
      the codes which could facilitate their comparison.

PMID- 12072846
TI  - Advances in computers and image processing with applications in nuclear medicine.
AB  - The continuing advances in hardware performance had made many previously
      computationally unattractive methods feasible, an example being iterative
      reconstruction in tomography, which is now routine. Dynamic SPECT can also be
      performed. However the aim of image processing is not just to produce pretty
      pictures, but to extract good clinical information. The methods also need to
      incorporate clinical knowledge and be defined using clinical constraints. In
      general data in nuclear medicine are n-D, often 3-D plus time. Data reduction for
      example by the extraction of physiological information, is important. Such data
      are in any case hard to visualise without compression, for example some kind of
      dimensionality reduction, going from n-D to a 2-D "functional" image. Both linear
      and non-linear operations can be considered. To extract physiological data, we
      need to fit models. Two classes of method are important: data driven and
      hypothesis driven. Examples of data driven methods are principal component
      analysis and factor analysis, where the model is derived form the data.
      Hypothesis driven methods are all implicitly or explicitly based on model
      fitting. A preliminary data driven step followed by an hypothesis driven approach
      could be called constrained statistical image analysis. Examples are shown as
      used in nuclear medicine and are being extended to MRI. Another important problem
      considered is that of multi-modality image registration and fusion. Although many
      methods exist, all based on the minimisation of an appropriate distance functions
      between 2 image data sets such as mutual information, additional constraints are
      required when the images are not so similar. Additional constraints can be
      imposed by means of cluster analysis of the n-dimensional feature space. In the
      analysis of such data, tests against reference data sets (atlases) are required,
      normally requiring warping the data sets in space, for example by the use of
      optic flow, or some kind of diffusion equation. Real time analysis of data during
      acquisition can lead to optimisation of acquisition procedures. Incorporation of
      such image analysis into a decision support system is desirable.

PMID- 12072847
TI  - Kinetic modeling in positron emission tomography.
AB  - Most PET kinetic modeling approaches have at their basis a compartmental model
      that has first-order, constant coefficients. The present article outlines the one
      , two-, and three-compartment models used to measure cerebral blood flow,
      cerebral glucose metabolism, and receptor binding, respectively. The number of
      compartments of each model is based on specific knowledge of the physiological
      and/or biochemical compartments into which the tracer distributes. Additional
      physical and biochemical properties of the tracer distribution are considered in
      specifying the use of first-order rate constants. For example, in cerebral blood
      flow and receptor binding studies transport across the blood-brain barrier by
      diffusion can be modeled as a first-order process. A saturable carrier-mediated
      process or saturable enzyme catalyzed reaction, when tracer doses of the labeled
      substrate are used and the natural substrate is in steady-state, also results in
      first-order rate constants, as in glucose metabolism studies. The rate of ligand
      binding, on the other hand, depends on the concentrations of both substrate and
      available receptors. In order to appropriately model the reaction as pseudo first
      order during a specified experimental interval, protocols are carefully designed
      to assure that the number of available binding sites remains approximately
      constant throughout the given interval. A broad array of scanning protocols is
      employed for kinetic analyses. These include single-scan approaches, which
      function like their autoradiographic counterparts in animal studies and are often
      called "autoradiographic" methods, which allow estimation of a single parameter.
      Dynamic scanning to obtain the time course of tissue activity allows simultaneous
      estimation of multiple parameters. Scanning may be conducted during a period of
      tracer uptake or after attainment of steady-state conditions. All quantitative
      modeling approaches share the common requirement that an arterial input function
      be measured or an appropriate surrogate be found. A vast array of methods is
      available for estimation of model parameters, both micro and macro. In the final
      analysis, it is the interaction among all elements of the PET study, including
      careful tracer selection, model specification, experimental protocol design, and
      sound parameter estimation methods, that determines the quantitative accuracy of
      the estimates of the physiological or biochemical process under study.

PMID- 12072848
TI  - Palpation of the upper thoracic spine: an observer reliability study.
AB  - OBJECTIVE: To assess the intraobserver reliability (in terms of hour-to-hour and
      day-to-day reliability) and the interobserver reliability with 3 palpation
      procedures for the detection of spinal biomechanic dysfunction in the upper 8
      segments of the thoracic spine. DESIGN: A repeated-measures design was used in
      all substudies. SETTING: Department of Nuclear Medicine, Odense University
      Hospital, Denmark. PARTICIPANTS: Two chiropractors examined 29 patients and 27
      subjects in the interobserver part and 1 chiropractor examined 14 patients and 15
      subjects in the intraobserver studies. INTERVENTION: Three types of palpation
      were performed: Sitting motion palpation and prone motion palpation for
      biomechanic dysfunction and paraspinal palpation for tenderness. Each dimension
      was rated as "absent" or "present" for each segment. All examinations were
      performed according to a standard written procedure. RESULTS: Using an "expanded"
      definition of agreement that accepts small inaccuracies (+/-1 segment) in the
      numbering of spinal segments, we found--based on the pooled data from the
      thoracic spine--kappa values of 0.59 to 0.77 for the hour-to-hour and the day-to
      day intraobserver reliability with all 3 palpation procedures. Kappa coefficients
      were 0.24 and 0.22 for the interobserver reliability with prone and sitting
      motion palpation and 0.67 and 0.70, respectively, with paraspinal palpation for
      tenderness. CONCLUSION: With expanded agreement we found good hour-to-hour and
      day-to-day intraobserver reliability with all 3 palpation procedures and good
      interobserver reliability for paraspinal tenderness. The interobserver
      reliability was unacceptably poor with prone and sitting motion palpation.

PMID- 12072849
TI  - Clinical considerations in the use of surface electromyography: three
      experimental studies.
AB  - BACKGROUND: The validity and applicability of erector spinae electromyogram (EMG)
      use in clinical practice is questionable. Differences in the amplitude of the EMG
      signal between populations with low back pain (LBP) and controls have been
      hypothesized but not sufficiently documented. OBJECTIVE: To examine issues of EMG
      asymmetry and repeatability in populations with LBP and populations without LBPin
      3 separate studies. STUDY DESIGN: Three separate experimental research studies.
      METHODS: Study 1 examined the intraclass correlation of the EMG signal of the
      paraspinal musculature at L3 on 3 separate days during quiet stance with use of 3
      different normalization techniques: percent maximum voluntary contraction,
      percent submaximal voluntary contraction, and percent averaged submaximal
      contractions. Study 2 used a population with chronic LBP to compare the bilateral
      asymmetry of paraspinal musculature in segments exhibiting pain with segments not
      exhibiting pain during quiet stance. A 1-way analysis of variance was used to
      compare differences between asymmetry scores in the pain and nonpain groups. In
      study 3, persons with LBP and persons in the control group had the dynamic
      asymmetry of paraspinal musculature compared during forward bending. A cross
      correlation coefficient assessing bilateral muscle activity was calculated for
      each subject and differences between groups were evaluated using a 1-way analysis
      of variance. RESULTS: Study 1: Subjects showed excellent repeatability (ICC >
      0.75) regardless of the normalization technique. Study 2: During quiet stance no
      differences were found in bilateral asymmetry between painful and nonpainful
      motion segments. Study 3: No differences existed in bilateral dynamic symmetry
      for the upper erector spinae; however, differences between groups did exist for
      the lower erector spinae. CONCLUSION: Repeatability of the EMG signal during
      quiet stance is acceptable; however, bilateral asymmetry may not be a definitive
      indicator of dysfunction.

PMID- 12072850
TI  - Expectations of chiropractic treatment: what are the expectations of new patients
      consulting a chiropractor, and do chiropractors and patients have similar
      expectations?
AB  - BACKGROUND: There are conflicting views about whether expectation plays a role in
      patient satisfaction. No studies regarding the importance of patient expectations
      have been done in the chiropractic field. OBJECTIVE: To investigate the
      expectations of new patients consulting a chiropractor and to evaluate
      differences and similarities in expectations between chiropractors and patients.
      DESIGN: A questionnaire survey. STUDY PARTICIPANTS: Thirty chiropractors and 336
      patients from 17 private practices throughout Sweden. RESULTS: Chiropractors and
      patients expected the chiropractor to find the problem and explain it to the
      patients, and they also expected patients to feel better and become free of
      symptoms. However, the following differences were revealed: patients had lower
      expectations of the chiropractic treatment than the chiropractors but higher
      expectations of being given advice and exercises than the chiropractors did.
      There was also a tendency for the patients to expect to get better faster than
      the chiropractors expected them to. CONCLUSION: Although chiropractors and
      patients had some common goals in relation to the therapeutic encounter, there
      was also a mismatch in certain areas. It is possible that these differences in
      expectations could influence the treatment and outcome of the treatment
      negatively. This reinforces the importance of communication between the
      chiropractor and the patients. More research is needed to evaluate whether
      fulfilment of expectations actually has an impact on patient satisfaction.

PMID- 12072851
TI  - A simplified conceptual model of the human cervical spine for evaluating force
      transmission in upright static posture.
AB  - OBJECTIVE: To develop a simplified graphical model appropriate for the evaluation
      of proposed theoretical force transmission mechanisms in the upright static
      cervical spine. The model is used to demonstrate in a visual format the
      underlying mechanical principles contributing to an optimal mechanical
      configuration of the cervical spine in upright posture. The model is also used to
      explore the relative mechanical efficiency of 2 different force transmission
      methods. METHOD: A graphical model was developed to illustrate relevant force
      vectors acting on the head and neck in upright posture. This model was used to
      calculate theoretical static loading on the structures of the neck under various
      loading conditions resulting from specific configurations of passive elements and
      active supportive muscle effort. RESULTS: From the information gained from the
      model, a theorized optimal mechanical configuration and theorized role of various
      components of the cervical spine in static upright posture is presented. The
      model is used to test the mechanical validity of a concurrent force system with
      intersegmental muscle force rather than the parallel force system presented in
      the literature. The alternate models are examined in relation to their
      predictions and theoretical implications with respect to force transmission in
      the cervical spine. CONCLUSION: A simplified model has been developed that
      facilitates the graphical representation of forces involved in maintaining static
      upright posture in the human cervical spine. The model is used to explore the
      optimal spinal configuration of the major mechanical components of the neck.

PMID- 12072852
TI  - Comparison of tibial nerve H-reflex excitability after cervical and lumbar spine
      manipulation.
AB  - BACKGROUND: Previous investigations indicate that spinal manipulation leads to
      short-term attenuation of alpha-motoneuron excitability, when assessed by means
      of the Hoffmann reflex. Past studies, however, are limited to regional effects,
      such as lumbar manipulation effects on lumbar alpha-motoneuron activity.
      OBJECTIVE: This study compared and contrasted the effects of cervical and lumbar
      spine manipulation on the excitability of the lumbar alpha-motoneuronal pool in
      human subjects without low back pain, and compared the effects of cervical
      (nonregional) and lumbar (regional) spinal manipulation on lumbar alpha
      motoneuron pool excitability in healthy subjects. The specific aim of this study
      was to determine if the inhibitory effects on the lumbar alpha-motoneuron pool
      associated with spinal manipulation are limited to the specific region in which
      the manipulative procedure is applied, or if rostral (cervical) manipulation can
      also influence caudal (lumbar) motoneuron excitability. METHOD: Thirty-six
      nonpatient human subjects were used to study the effect of cervical and lumbar
      spinal manipulation on the amplitude of the tibial nerve Hoffmann reflex,
      recorded from the gastrocnemius muscle. The Hoffmann reflex (H-reflex) technique
      allows for an indirect index of motoneuron pool excitability by means of
      peripheral nerve Ia-afferent fiber stimulation. Reflexes were recorded before and
      after spinal manipulative procedures. RESULTS: Lumbar spinal manipulation, as
      measured by amplitude changes of the tibial nerve H-reflex, attenuated lumbar
      alpha-motoneuronal activity. Suppression of motoneuronal excitability was
      significant (P <.05) but transient, with a return to baseline within 60 seconds
      after manipulation. Cervical spinal manipulation had no significant effect on
      lumbar motoneuron activity. CONCLUSION: These data indicate that the inhibitory
      effects of spinal manipulation on motoneuronal excitability are regional, rather
      than global.

PMID- 12072856
TI  - Osteogenesis imperfecta in a weightlifter.
AB  - OBJECTIVE: To discuss the case of a 42-yr-old weightlifter with osteogenesis
      imperfecta. CLINICAL FEATURES: The patient had bilateral acute elbow pain and a
      previous history of more than 35 fractures of the spine and extremities.
      INTERVENTION: There is no current treatment for osteogenesis imperfecta.
      Treatment objectives were designed to minimize pain, improve range of motion, and
      decrease stress on the elbow joints. Nutritional supplementation was used to help
      maintain bone density. The elbow pain improved with treatment, and the patient
      has had no new fractures in the last 6 years. CONCLUSION: Although most patients
      with osteogenesis imperfecta are physically inactive because of the high risk of
      fracture, some patients with milder forms of the condition may be involved in
      some athletic activities. Although manipulation is contraindicated in patients
      with osteogenesis imperfecta, chiropractors may be of service by offering pain
      relief and rehabilitation, in addition to advice regarding nutrition and
      supplements.

PMID- 12072853
TI  - Can custom-made biomechanic shoe orthoses prevent problems in the back and lower
      extremities? A randomized, controlled intervention trial of 146 military
      conscripts.
AB  - BACKGROUND: Shock-absorbing and biomechanic shoe orthoses are frequently used in
      the prevention and treatment of back and lower extremity problems. One review
      concludes that the former is clinically effective in relation to prevention,
      whereas the latter has been tested in only 1 randomized clinical trial,
      concluding that stress fractures could be prevented. OBJECTIVES: To investigate
      if biomechanic shoe orthoses can prevent problems in the back and lower
      extremities and if reducing the number of days off-duty because of back or lower
      extremity problems is possible. DESIGN: Prospective, randomized, controlled
      intervention trial. STUDY SUBJECTS: One female and 145 male military conscripts
      (aged 18 to 24 years), representing 25% of all new conscripts in a Danish
      regiment. METHOD: Health data were collected by questionnaires at initiation of
      the study and 3 months later. Custom-made biomechanic shoe orthoses to be worn in
      military boots were provided to all in the study group during the 3-month
      intervention period. No intervention was provided for the control group.
      Differences between the 2 groups were tested with the chi-square test, and
      statistical significance was accepted at P <.05. Risk ratio (RR), risk difference
      (ARR), numbers needed to prevent (NNP), and cost per successfully prevented case
      were calculated. OUTCOME VARIABLES: Outcome variables included self-reported back
      and/or lower extremity problems; specific problems in the back or knees or shin
      splints, Achilles tendonitis, sprained ankle, or other problems in the lower
      extremity; number of subjects with at least 1 day off-duty because of back or
      lower extremity problems and total number of days off-duty within the first 3
      months of military service because of back or lower extremity problems. RESULTS:
      Results were significantly better in an actual-use analysis in the intervention
      group for total number of subjects with back or lower extremity problems (RR 0.7,
      ARR 19%, NNP 5, cost 98 US dollars); number of subjects with shin splints (RR
      0.2, ARR 19%, NNP 5, cost 101 US dollars); number of off-duty days because of
      back or lower extremity problems (RR 0.6, ARR < 1%, NNP 200, cost 3750 US
      dollars). In an intention-to-treat analysis, a significant difference was found
      for only number of subjects with shin splints (RR 0.3, ARR 18%, NNP 6 cost 105 US
      dollars), whereas a worst-case analysis revealed no significant differences
      between the study groups. CONCLUSIONS: This study shows that it may be possible
      to prevent certain musculoskeletal problems in the back or lower extremities
      among military conscripts by using custom-made biomechanic shoe orthoses.
      However, because care-seeking for lower extremity problems is rare, using this
      method of prevention in military conscripts would be too costly. We also noted
      that the choice of statistical approach determined the outcome.

PMID- 12072858
TI  - Mechanical force spinal manipulation increases trunk muscle strength assessed by
      electromyography: a comparative clinical trial.

PMID- 12072857
TI  - Pathologic fracture of metacarpal enchondroma: case study and differential
      diagnosis.
AB  - OBJECTIVE: To discuss a case of enchondroma initially appearing as a pathologic
      fracture in a metacarpal bone. The recommended treatment for a pathologic
      fracture of an enchondroma in the hand is reviewed. Additionally, a reasonable
      list of differential considerations is presented with accompanying radiographic
      and advanced imaging characteristics. CLINICAL FEATURES: A 25-year-old male
      chiropractic student had a painful, bruised, and swollen thumb following athletic
      trauma. Radiographs showed a pathologic comminuted fracture of the first
      metacarpal, with a resultant anterior angulation of the distal fragment. Fracture
      occurred through a well-defined, geographic, lucent lesion in the proximal
      metaphysis consistent with enchondroma. INTERVENTION AND OUTCOME: Closed
      reduction of the fracture and casting were used. No treatment was administered
      for the enchondroma. Adequate healing of the fracture took place with residual
      angulation at the fracture site. Size and extent of the enchondroma were
      unchanged after fracture healing. CONCLUSIONS: Recommended treatment for a
      pathologic fracture through an enchondroma in the hand is casting, which allows
      fracture healing. Curettage of the lesion without packing of the resultant cavity
      is then recommended. In this case, casting and fracture healing took place
      without any treatment directed at the enchondroma. The patient was advised of the
      rationale for undergoing the removal of the enchondroma. Removal was recommended
      to prevent fracture recurrence from structural weakening, which would be likely
      due to the unusually high level of mechanical stress from the professional
      demands of manual treatment.

PMID- 12072859
TI  - Unsubstantiated claims in patient brochures from the largest state, provincial,
      and national chiropractic associations and research agencies.

PMID- 12072860
TI  - Rapid progression of acute sciatica to cauda equina syndrome.

PMID- 12072862
TI  - Evolution of subspecialty care in pediatrics.

PMID- 12072863
TI  - Relationship between obesity and sleep-disordered breathing in children: is it a
      closed loop?

PMID- 12072864
TI  - The association of tachycardia with obesity and elevated blood pressure.

PMID- 12072865
TI  - The impact of neonatal intensive care practices on the developing brain.

PMID- 12072866
TI  - Metabolic correlates with obstructive sleep apnea in obese subjects.
AB  - OBJECTIVE: To examine links between obstructive sleep apnea (OSA), insulin
      resistance, and dyslipidemia. STUDY DESIGN: Obese (body mass index [BMI] >95th
      percentile for age and gender) children who snored (n = 62, 46 males, age 10.89
      [5-16 years] underwent polysomnography and metabolic studies. RESULTS:
      Respiratory disturbance index (RDI) was 9.23 (0-95), with 23 children (39%)
      recommended for treatment. Fasting insulin levels were 154.6 pmol/L +/- 79.8 (52
      486), and fasting glucose levels were high in 7 children (11%). Fasting insulin
      levels correlated with sleep variables, including log transformed RDI
      (log(10)RDI) (P =.01), desaturation events (P =.05), arousal index (P =.01), and
      sleep-time with oxygen saturation in arterial blood <90% (P =.03) (adjusted r (2)
      = 0.21, F = 3.9, P =.005), but not with age, or BMI Z score. Log(10)RDI
      correlated with fasting insulin (P =.001) and BMI Z score (P =.03) (adjusted r
      (2) = 0.12, F = 3.9, P =.005), but not age or other metabolic variables. The
      correlation between log(10)RDI and fasting insulin persisted in models combining
      sleep and metabolic variables: log(10)RDI, adjusted r (2) = 0.75, F = 35.2, P
      <.001, and for fasting insulin, adjusted r (2) = 0.42, F = 6.1, and P <.001.
      CONCLUSIONS: The severity of OSA (log(10)RDI) correlated with fasting insulin
      levels, independent of BMI. Insulin levels may be further elevated as a
      consequence of OSA in obese children.

PMID- 12072867
TI  - Isolated systolic hypertension, obesity, and hyperkinetic hemodynamic states in
      children.
AB  - OBJECTIVE: To determine the factors that contribute to the pathogenesis of
      isolated systolic hypertension in children. METHODS: School-based measurement was
      performed of blood pressure (BP), heart rate, weight, and height in 2460 students
      (49% Hispanic, 31% black, 13% white) 12 to 16 years of age in 8 urban public
      schools. An independent group of 71 untreated children underwent 24-hour
      ambulatory BP monitoring (ABPM) to confirm clinic hypertension and assess
      circadian BP patterns. RESULTS: Hypertension and obesity were found in 17% and
      23% of students, respectively. Among hypertensive students, 88% (363/413) had
      isolated systolic hypertension. Hypertension was more prevalent in obese than
      nonobese students (33% vs 11%, P <.0001). Obese hypertensive students had higher
      resting heart rate than nonobese normotensive patients (85.9 vs 79.6 beats/min, P
      <.001). Among patients who underwent ABPM, isolated systolic hypertension was
      found in 51% (36/71) by clinic BP and in 62% (18/29) with confirmed hypertension
      by ABPM. Blood pressure variability during daytime and sleep periods was higher
      in obese than nonobese patients for systolic BP (P <.01) and diastolic BP (P
      <.05). CONCLUSIONS: The findings of increased heart rate and BP variability in
      obese children with isolated systolic hypertension suggest that sympathetic
      nervous system hyperactivity may contribute to its pathogenesis.

PMID- 12072868
TI  - Sociodemographic determinants of added sugar intake in preschoolers 2 to 5 years
      old.
AB  - OBJECTIVES: To determine sociodemographic predictors of added sugar intake from a
      national representative sample of 2- to 5-year-old children. STUDY DESIGN: Cross
      sectional study that used dietary intake data of the US Department of Agriculture
      Continuing Survey of Food Intake in Individuals 1994 to 1996 and 1998 (n = 5652).
      Amount of added sugar intake in teaspoons per day, teaspoons per 100 kcal, and
      percent of total energy was calculated by selected sociodemographic variables,
      accounting for sample design and weighted to permit inferences applicable to the
      total population. Multivariate linear regression analysis was used to predict
      added sugar intake. RESULTS: Average added sugar consumption was 15.4 tsp/d
      (15.7% of total energy). Significant differences were observed by several socio
      demographic characteristics. Multivariate models predicting energy-adjusted
      intake indicated strong associations with age, ethnicity, income, day care/school
      attendance, Supplemental Program for Women, Infants, and Children (WIC)
      participation, region of residence, and female head of household's educational
      level. CONCLUSIONS: The identified sociodemographic predictors of high added
      sugar intake might help target public health messages to improve children's diet
      quality and prevent future chronic diseases to population groups at highest risk.

PMID- 12072869
TI  - Differences in insulin secretion and sensitivity of Caucasian and African
      American prepubertal children.
AB  - OBJECTIVE: To investigate whether differences in body composition of African
      American children (AA) and Caucasian children (C) explain differences in insulin
      sensitivity and secretion. STUDY DESIGN: Prepubertal nondiabetic children (31 AA
      and 54 C) were studied; 84% were overweight. Participants underwent a 2-hour
      hyperglycemic clamp, to estimate insulin sensitivity (SI(clamp)) and secretion,
      and dual energy x-ray absorptiometry, to assess body composition. RESULTS: AA had
      greater total body fat mass (P =.01), fasting, 1st phase, 2nd phase, and steady
      state insulin levels (P <.05). AA and C had similar glucose disposal rates, but
      AA had lower SI(clamp) (P <.05). Fasting, 1st phase, and steady state C-peptide
      were less in C (P <.05), whereas corresponding C-peptide/insulin ratios were
      higher (all P <.005). Insulin levels and SI(clamp) remained different in AA and C
      after adjustment for body fat or lean mass differences. Analyses restricted to
      only overweight AA and C showed similar trends. CONCLUSION: Prepubertal African
      American children have higher baseline and glucose-stimulated insulin and C
      peptide levels, as well as reduced insulin sensitivity that is not entirely
      explained by differences in adiposity. The lower C-peptide/insulin molar ratio in
      AA suggests that they probably have lower hepatic insulin clearance than
      Caucasian children.

PMID- 12072870
TI  - Bioelectrical impedance analysis of the body composition of children and
      adolescents with sickle cell disease.
AB  - OBJECTIVES: To examine the body composition of children and adolescents with
      sickle cell disease (SCD) using bioelectrical impedance analysis and to determine
      if the impedance parameters resistance, reactance, and phase angle are able to
      distinguish between subjects with SCD and age- and gender matched controls. STUDY
      DESIGN: Total body resistance and reactance were obtained for a total of 53
      subjects with SCD (27 male and 26 female) between 10 and 18 years of age and 49
      control subjects (23 male and 26 female). The fat-free mass, body cell mass,
      phase angle, and capacitance were also determined. Group comparisons were made
      using the 2-sample t test. RESULTS: Male subjects with SCD had significantly
      lower fat-free mass (37.5 +/- 8.8 vs 43.9 +/- 12.3 kg, P =.04), body cell mass
      (17.4 +/- 4.3 vs 21.7 +/- 5.8 kg,P =.005), and body fat (3.7 +/- 2.6 vs 6.6 +/-
      4.7 kg, P =.008) compared with controls. No significant differences in any body
      composition components were found for the female subjects. Both male and female
      subjects had significantly lower phase angle measurements (P <.001 and.006,
      respectively) than their respective controls, indicating possible alterations in
      cell membrane properties because of an imbalance in membrane composition or
      function. CONCLUSIONS: Bioelectrical impedance analysis can be used to determine
      body composition differences in children with SCD. The phase angle may provide a
      useful method to monitor the efficacy of therapeutic interventions in patients
      with SCD.

PMID- 12072871
TI  - The effect of the Val34Leu polymorphism in the factor XIII gene in infants with a
      birth weight below 1500 g.
AB  - OBJECTIVES: The 34Leu polymorphism of the factor XIII gene is associated with a
      low rate of brain infarction and a higher incidence of primary intracerebral
      hemorrhage in adults. We evaluated the effect of the polymorphism on the
      subsequent development of isolated intracranial hemorrhage and white matter
      disease in preterm infants with a birth weight <1500 g (very low birth weight
      [VLBW] infants). STUDY DESIGN: We studied 531 VLBW infants and 301 control
      infants born at term. The factor XIII 34Leu polymorphism was detected by
      polymerase chain reaction and restriction enzyme digestion. RESULTS: Allele
      frequencies were not different from term and VLBW infants (Val/Val, 53.1% and
      57.8%; Val/Leu, 38.8% and 37.6%; Leu/Leu, 8.0% and 4.5%, respectively). VLBW
      infants carrying the Leu/Val or Leu/Leu allele had a significant reduced risk of
      the development of white matter disease (3.6% vs 10.4% in infants without the
      polymorphism, P =.003). In a multivariate logistic regression analysis, only
      gestational age <28 weeks (odds ratio, 3.8; 95% confidence interval, 1.9-7.5; P
      <.001), and the factor XIII 34Leu allele (odds ratio, 0.3; 95% confidence
      interval, 0.1-0.7; P =.005) had significant prognostic value in predicting
      subsequent white matter disease. However, VLBW infants who carried the factor
      XIII 34Leu allele also had a moderately increased risk of the subsequent
      development of isolated intraventricular hemorrhage (14.3% vs 10.1% in infants
      without the mutation, P =.17). CONCLUSIONS: VLBW infants carrying the factor XIII
      34Leu polymorphism had a decreased risk for white matter disorders.

PMID- 12072872
TI  - Endogenous pulmonary surfactant metabolism is not affected by mode of ventilation
      in premature infants with respiratory distress syndrome.
AB  - OBJECTIVE: To determine if high frequency oscillatory ventilation (HFOV)
      decreases surfactant production in premature infants with respiratory distress
      syndrome (RDS). STUDY DESIGN: We randomized 19 infants <28 weeks of gestation to
      either HFOV (n = 8) or conventional ventilation (CV, n = 11) at 24 hours of life.
      After a 24-hour continuous infusion of uniformly labeled carbon 13 glucose (U
      (13)C(6)) glucose, we measured (13)C enrichment in surfactant phosphatidylcholine
      (PC) in tracheal aspirate samples using gas chromatography/mass spectrometry. We
      calculated the fractional synthetic rate (FSR) of surfactant PC from labeled
      glucose and its half-life of clearance (T(1/2)). RESULTS: FSR did not differ
      between groups (4.7% +/- 2.7%/day CV vs 4.2% +/- 3.1%/day HFOV, P =.7). T(1/2)
      was 79 +/- 18 hours in the CV group and 76 +/- 23 hours in the HFOV group (P
      =.7). Neither degree of ventilatory support nor supplemental oxygen exposure
      correlated with surfactant metabolic indices. Three of 4 infants who died from
      RDS within the first month of life had a shorter T(1/2) than 14 of 15 infants who
      survived. CONCLUSION: Surfactant metabolism is similar in preterm infants
      ventilated with HFOV and CV. Shortened surfactant half-life may characterize a
      subset of preterm infants with lethal RDS.

PMID- 12072873
TI  - The Newborn Individualized Developmental Care and Assessment Program is not
      supported by meta-analyses of the data.
AB  - OBJECTIVES: To systematically review the effectiveness of the Newborn
      Individualized Developmental Care and Assessment Program (NIDCAP) as compared
      with conventional care to improve long-term neurodevelopmental outcomes or short
      term medical and neurodevelopmental outcomes in preterm and/or low birth weight
      infants. STUDY DESIGN: With the use of standard systematic review methodology,
      all randomized, controlled trials (RCTs) and prospective cohort studies
      evaluating in-hospital developmental care based on the framework of NIDCAP in
      preterm and/or low birth weight infants were identified. The quality of the RCTs
      was assessed. Meta-analyses were performed by using relative risk and risk
      difference for dichotomous data and weighted mean difference for continuous data
      with 95% confidence intervals. RESULTS: Five RCTs (n = 136) and 3 phase-lag
      cohort studies (n = 185) met inclusion criteria. School-age neurodevelopmental
      outcomes after NIDCAP have not been reported. Meta-analyses of medical outcomes
      showed a statistically significant benefit of NIDCAP on requirement for
      supplemental oxygen. Neurodevelopmental outcome was improved at 9 or 12 months
      but not at 2 years. CONCLUSIONS: There is insufficient evidence to support the
      NIDCAP to improve medical and neurodevelopmental outcomes of preterm infants.

PMID- 12072874
TI  - Prediction of outcome based on clinical seizure type in newborn infants.
AB  - OBJECTIVE: To determine whether the clinical features of neonatal seizures are of
      value in predicting outcome. STUDY DESIGN: Demographic features, clinical seizure
      types, etiologic factors, and laboratory findings of all 77 patients with
      seizures admitted to our neonatal intensive care unit over a consecutive 7-year
      period were extracted from the medical records. RESULTS: Twenty-three (30%) died;
      59% of the survivors had abnormal neurologic examinations, 40% were mentally
      retarded, 43% had cerebral palsy, and 21% were epileptic at mean follow-up of 3.5
      years. Compared with patients with other seizure types, those with subtle and
      generalized tonic seizures had a significantly higher prevalence of epilepsy (P
      =.04 and P =.01 respectively); mental retardation (P =.02; P =.007), and cerebral
      palsy (P =.03; P =.002). Subtle seizures were, in addition, more likely to be
      associated with abnormalities on the neurologic examination at follow-up (P
      =.03). Similar outcome comparisons for those with focal and multifocal clonic,
      focal tonic, and multifocal myoclonic seizures revealed no significant
      differences. However, patients with >or=2 seizure types were significantly more
      likely to have epilepsy (P =.02), mental retardation (P =.001), cerebral palsy (P
      =.001), and abnormal examinations (P =.05). CONCLUSIONS: Clinical semiology is
      predictive of outcome in neonates with seizures and suggests the presence of
      unique pathophysiologic processes for different seizure types.

PMID- 12072876
TI  - Motor dysfunction of the upper digestive tract in Pierre Robin sequence as
      assessed by sucking-swallowing electromyography and esophageal manometry.
AB  - OBJECTIVES: To evaluate motor dysfunction in infants with Pierre Robin sequence
      (PRS) who manifest upper airway obstruction and congenital dysphagia. STUDY
      DESIGN: Term infants (n = 28) with nonsyndromic PRS were studied between days 15
      and 45. Sucking-swallowing electromyography was used to evaluate suction and
      coordination between the oral and pharyngeal phases of swallowing. Esophageal
      manometry was used to study the lower esophageal sphincter, esophageal body, and
      upper esophageal sphincter functions. Manometry results were compared with those
      of 16 infants with gastroesophageal reflux disease (GERD). RESULTS:
      Electromyography showed incoordination of sucking and swallowing in 24 of 28
      patients. The disorder was mild in 6, moderate in 6, and severe in 12 patients.
      All patients showed manometry disturbances: incomplete or asynchronous lower
      sphincter relaxation (15), multipeaked esophageal body waves (17), very high
      amplitude waves (14), and asynchronous upper sphincter relaxation (19). The
      frequency of disturbances and mean resting pressures of both lower and upper
      sphincters were significantly higher than GERD patients. CONCLUSION: In Pierre
      Robin sequence, sucking-swallowing electromyography and esophageal manometry
      reveal dysfunction in the motor organization of the tongue, the pharynx, and the
      esophagus.

PMID- 12072875
TI  - Fear of litigation may increase resuscitation of infants born near the limits of
      viability.
AB  - OBJECTIVES: To explore how fear of litigation influences neonatal treatment
      decisions. STUDY DESIGN: In a mailed survey, we presented a hypothetical vignette
      of a premature infant to 1000 neonatologists. We asked them to estimate
      prognosis, indicate appropriate intervention, and respond to parental treatment
      requests. Subjects were randomly assigned to receive one of two questionnaires,
      "litigious" or "nonlitigious," which differed only in the description of the
      infant's parents. RESULTS: The response rate was 63.0%. The vast majority of
      respondents deferred to parental requests rather than adhering to their best
      judgment. They deferred whether or not parents requested treatment and whether or
      not parents were described as litigious (P <.0001). Among those respondents who
      shifted their resuscitation opinion after parental introduction, respondents to
      the nonlitigious version were more likely to shift their opinion from "treat" to
      "do not treat" after parental requests to "use your best judgment" (P <.042). The
      influence of parental litigiousness was primarily seen among neonatologists who
      thought that the infant's prognosis was dismal (P <.044). CONCLUSIONS: There is a
      strong disposition among neonatologists toward respecting parental wishes. This
      disposition is stronger when neonatologists are given additional reason to be
      concerned about litigation.

PMID- 12072877
TI  - Early diagnosis of ataxia-telangiectasia using radiosensitivity testing.
AB  - OBJECTIVES: To utilize radiosensitivity testing to improve early diagnosis of
      patients with ataxia-telangiectasia (A-T). STUDY DESIGN: We established normal
      ranges for the colony survival assay (CSA) by testing cells from 104 patients
      with typical A-T, 29 phenotypic normal patients, and 19 A-T heterozygotes. We
      also analyzed 61 samples from patients suspected of having A-T and 25 patients
      with related disorders to compare the CSA with other criteria in the diagnosis of
      A-T. RESULTS: When cells were irradiated with 1.0 Gy, the mean survival fraction
      (microSF +/- 1 SD) for patients with A-T was 13.1% +/- 7.2% compared with 50.1%
      +/- 13.5% for healthy control patients. These data served to define a diagnostic
      range for the CSA (ie, <21%), a normal range (>36%), and a nondiagnostic
      intermediate range of 21% to 36%. The mutations of patients with A-T with
      intermediate radiosensitivity tended to cluster around the functional domains of
      the ATM gene. CONCLUSIONS: The CSA is a useful adjunctive test for confirming an
      early clinical diagnosis of A-T. However, CSA is also abnormal in other
      chromosomal instability and immunodeficiency disorders.

PMID- 12072878
TI  - Mosaic or chimera? Revisiting an old hypothesis about the cause of the
      46,XX/46,XY hermaphrodite.
AB  - OBJECTIVES: A cell lineage in a hermaphrodite infant showing a 46,XX/46,XY
      karyotype was analyzed to determine the genetic contribution from both parents
      and identify the underlying mechanism. STUDY DESIGN: Genotype analysis was
      performed by using 57 microsatellite markers, 39 distributed on 9 autosomes and
      18 on the X-chromosome. Two X- and Y-specific markers were analyzed to confirm
      the presence and percentages of cells containing a Y-chromosome. RESULTS: The
      proband revealed a single maternal and paternal allele for all of the informative
      autosomal and X-chromosome markers. Analysis of the X- and Y-specific markers
      confirmed that approximately 20% of the patient's peripheral blood cells
      contained the Y chromosome. CONCLUSIONS: The data suggest that the patient's
      hermaphroditism was the result of a mosaic embryo and not a chimera. The most
      likely mechanism involved 2 separate nondisjunction events, resulting in the loss
      of 47,XXY cells during early embryonic development.

PMID- 12072879
TI  - Outcome of ventricular septal defect repair in a developing country.
AB  - OBJECTIVES: To examine the impact of nutrition and lung infection on outcome
      early after ventricular septal defect (VSD) repair in infants in a developing
      country. STUDY DESIGN: One hundred consecutive infants (age, 7.4 +/- 3.3 months)
      with large VSD(s) who underwent surgical repair at one institution in South India
      from July 1998 to June 2000 were analyzed. Primary outcome variables were
      postoperative death, duration of mechanical ventilation, intensive care unit
      (ICU) stay, and hospital stay. Preoperative variables analyzed included age,
      weight and length Z scores, and lung infection. RESULTS: Preoperative nutrition
      was poor (weight Z score, -2.8 +/- 1.3), and 25 patients had pneumonia. Six
      patients died after repair. No preoperative variable was associated with death.
      Mechanical ventilation, ICU stay, and hospital stay were longer for younger
      patients (r (s) for ventilation, -0.23, P =.02; for ICU stay, -0.33, P <.001; for
      hospital stay, -0.27, P =.007) and for those with preoperative pneumonia (median
      ventilation duration, 46 vs 24 hours, P <.001; median ICU stay 7 vs 4 days, P
      <.001; median hospital stay 10 vs 7 days, P =.001). Preoperative weight and
      length Z scores were not associated with any outcome variable. CONCLUSIONS: Poor
      nutritional status, preoperative pneumonia, and age do not increase mortality
      rates after VSD repair. Repair of large VSDs should not be delayed because of
      these preoperative characteristics.

PMID- 12072880
TI  - Prevalence of superantigen-secreting bacteria in patients with Kawasaki disease.
AB  - OBJECTIVES: To assess the prevalence of superantigen secreting bacteria in
      children with acute Kawasaki disease (KD) relative to control patients. STUDY
      DESIGN: Bacterial cultures were obtained in a blinded fashion from the throat,
      rectum, and groin of 45 patients with untreated acute KD and 37 febrile control
      patients from 6 centers in the United States. Cultures were processed for the
      presence of superantigen-producing bacteria at a central laboratory. RESULTS:
      Staphylococci or streptococci that produced superantigens (TSST-1, SEB, SEC,
      SPEB, SPEC) were isolated from 25 of 45 patients with KD (56%) as compared with
      13 of 37 (35%) control patients (P =.078). Because SEB- and SEC-producing
      Staphylococcus aureus have not been associated with KD and because they do not
      induce a Vbeta2+ T-lymphocyte response, we analyzed the difference between groups
      relative to superantigens TSST-1 or SPEB/SPEC production. TSST-1 secreting S
      aureus or SPEB/SPEC producing group A streptococci were isolated from 20 of 45
      (44%) patients with KD compared with 7 of 37 (19%) control patients (P =.019).
      CONCLUSIONS: The overall isolation rates of superantigen (TSST-1, SPEB, SPEC,
      SEB, SEC) producing bacteria between patients with KD and febrile control
      patients were not statistically significant. However, future studies should
      further examine the potential role of Vbeta2-stimulatory superantigens (TSST-1
      and SPEB/SPEC) in KD.

PMID- 12072881
TI  - Parental anxiety associated with referral of a child to a pediatric cardiologist
      for evaluation of a Still's murmur.
AB  - OBJECTIVE: We assessed factors contributing to parental anxiety when children are
      referred to a cardiology clinic for evaluation of a Still's murmur. METHODS:
      Parents of 95 children completed questionnaires designed to assess family and
      patient characteristics, parents' ratings of their anxiety and the reassurance
      they received from their pediatrician, and current (state) and general anxiety
      levels. RESULTS: Parents reported anxiety about multiple issues including the
      need for medication (49%), sports restrictions (41%), cardiac surgery (29%),
      cardiac risk for siblings (20%), and premature death (13%). Of reporting mothers,
      19% felt the murmur resulted from something they did wrong during pregnancy.
      Although 54% of parents were extremely reassured by their pediatrician, only 17%
      had no anxiety associated with the specialty visit. After reassurance from the
      cardiologist, 7% of parents had persistent anxiety. In multivariable analysis, 2
      features, both related to the referring pediatrician, were significantly related
      to parental anxiety level. High parental anxiety was associated with lower
      pediatrician reassurance ratings and greater pediatrician practice years.
      CONCLUSIONS: Parental anxiety is common among parents of children referred for
      specialty evaluation. Educational strategies to improve pediatrician
      communication skills with parents may improve quality of care.

PMID- 12072883
TI  - Clinicopathologic conference: loss of milestones and failure to thrive in a 28
      month-old boy.

PMID- 12072882
TI  - Language skills in children with velocardiofacial syndrome (deletion 22q11.2).
AB  - OBJECTIVE: To further define the language profile of children with
      velocardiofacial syndrome (VCFS) and explore the influence of parental origin of
      the deletion on language. STUDY DESIGN: Children and adolescents with VCFS (n =
      27) were group-matched for sex, age, and IQ with 27 children and adolescents with
      idiopathic developmental delay. Fifty-four typically developing control subjects
      were also included in the analyses investigating word association abilities.
      RESULTS: Children with VCFS had significantly lower receptive than expressive
      language skills, a unique finding when compared with IQ-matched control subjects.
      However, no significant differences in word association were detected. Children
      with a deletion of paternal origin score significantly higher on receptive
      language when compared with children with a deletion of maternal origin.
      CONCLUSIONS: The Clinical Evaluation of Language Fundamentals-III results suggest
      that children with VCFS show more severe deficits in receptive than expressive
      language abilities. Language skills of children with VCFS could be influenced by
      parental origin of the deletion and thus related to neuroanatomic alterations at
      the deletion site.

PMID- 12072885
TI  - Estimation of the length of nasotracheal tube to be introduced in children.
AB  - The formula 10.5 + (weight[kg]/2) showed a predictive capacity of 0.8939 to
      estimate the length (cm) of endotracheal tube to be introduced through the nasal
      route in 99 children between newborn and 4 years old. In a validation study, the
      formula maintained a high level of concordance with the true values: 0.9370.

PMID- 12072884
TI  - Sleep organization is unaffected by caffeine in premature infants.
AB  - We performed 10-hour polysomnographic recordings in 15 neurologically normal and
      clinically stable 33- to 34-week postmenstrual age (PMA) neonates, 10 of whom had
      been treated >3 days with once-per-day oral caffeine citrate (5 mg/kg) given at
      approximately 2 PM. We analyzed (a) the usual sleep-wake variables, including
      wakefulness, active sleep, quiet sleep, and indeterminate sleep expressed as the
      number of episodes, duration, and percentage of total sleep time; (b) the
      duration and order of variable modifications during transitions between the main
      active sleep and quiet sleep states; and (c) the characteristics of morning data
      (before caffeine) compared with evening data (after caffeine). We found no
      significant differences between the controls and the infants receiving
      maintenance caffeine.

PMID- 12072886
TI  - Helicobacter pylori stool antigen test: a method to confirm eradication in
      children.
AB  - We evaluated an antigen-based stool assay as an indicator of Helicobacter pylori
      (Hp) status during treatment aimed at eradicating Hp in 22 Hp-positive patients
      and 63 negative control patients. The sensitivity and specificity of the assay
      was 100% and 70%, respectively, when the manufacturer's cutoff was used. When we
      used the cutoff calculated from a receiver operating characteristic curve, the
      specificity of this test increased. Under these conditions, the test could be
      used in monitoring treatment and verifying eradication of Hp infection. Further
      studies must be carried out to standardize the cutoff in children.

PMID- 12072887
TI  - The diagnosis of mitochondrial HMG-CoA synthase deficiency.
AB  - Deficiency of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, the only
      disorder exclusively affecting hepatic ketogenesis, is a cause of hypoglycemic
      coma. We report that the diagnosis can be made by typical laboratory findings
      (hypoketosis, elevated free fatty acids, normal acylcarnitines, specific urinary
      organic acids) during acute episodes.

PMID- 12072888
TI  - Glycogen synthase deficiency (glycogen storage disease type 0) presenting with
      hyperglycemia and glucosuria: report of three new mutations.
AB  - Although glycogen storage disease type 0 (GSD0) is included in the differential
      diagnosis of ketotic hypoglycemia, it usually is not considered in the evaluation
      of glucosuria or hyperglycemia. We describe two children with GSD0, confirmed by
      mutation analysis, who had glucosuria and hyperglycemia. Because of the variable
      presentation of this disorder and previous dependence on liver biopsy to confirm
      diagnosis, it is likely that GSD0 is underdiagnosed.

PMID- 12072889
TI  - Cutting the cord.

PMID- 12072890
TI  - Cardiac tamponade with peripherally inserted central catheters.

PMID- 12072892
TI  - Pulmonary complications associated with Kawasaki disease.

PMID- 12072893
TI  - Is phototherapy safe?

PMID- 12072894
TI  - Nifedipine in the treatment of hypertension in children.

PMID- 12072896
TI  - Short-term treatment with mycophenolic acid increases bile flow in continuously
      perfused and cold-preserved rat livers and does not affect hepatic ischemia
      reperfusion injury.
AB  - Mycophenolate mofetil (MMF) is a new immunosuppressive agent which has been used
      successfully after kidney and heart transplantation. Experience with MMF after
      liver transplantation is still limited. In particular, there is no information
      about influence on ischemia-reperfusion injury (IRI). Therefore, the aim of this
      investigation was to assess the effects of mycophenolic acid (MPA), the
      pharmacologically active metabolite of MMF, in the cold-preserved or normal rat
      liver. Livers of male Sprague-Dawley rats were subjected to cold ischemia in
      University of Wisconsin (UW) solution (24 h, 4 degrees C) and reperfused for 2 h
      in the absence or presence of MPA (100 microg/ml, n=5-6 each). Another group
      received MPA pretreatment for 20 min prior to ischemia ( n=7). In further
      experiments, livers were perfused with a bile salt-free Krebs-Henseleit buffer in
      a continuous fashion (controls, n=5). MPA was infused from 20-40 min after
      starting perfusion in therapeutic concentrations (5 microg/ml, 10 microg/ml, 40
      microg/ml, and 100 microg/ml; n=3-6 each). There was no significant influence of
      MPA on portal pressure nor on postischemic efflux rates of LDH. MPA pretreatment
      resulted in a significant improvement of bile flow during reperfusion (0.32+/
      0.05 microl/min x g liver) compared with controls (0.17+/-0.04 microl/min x g
      liver, mean+/-SEM). In contrast, postischemic bile flow was not influenced by
      continuous administration of MPA during the reperfusion period only (0.18+/-0.07
      microl/min x g liver). In continuously perfused livers, MPA increased bile salt
      independent bile flow (1.00+/-0.06 microl/min x g liver) in a dose-dependent
      manner, reaching half-maximal effects around 5 microg/ml (1.66+/-0.15 microl/min
      x g liver) and maximal effects at 40 microg/ml (2.61+/-0.28 microl/min x g
      liver). In conclusion, neither preischemic nor postischemic administration of MPA
      influences IRI to hepatocytes significantly after hypothermic liver preservation
      in UW solution. In contrast to other immunosuppressive agents, MPA exhibits
      strong choleretic effects, which are related to a stimulation of bile salt
      independent bile formation.

PMID- 12072897
TI  - Hepatic reticuloendothelial function during parenteral nutrition including an
      MCT/LCT or LCT emulsion after liver transplantation - a double-blind study.
AB  - It has been demonstrated that total parenteral nutrition (TPN) modulates the
      function of the hepatic reticuloendothelial system (RES). The objective of this
      study was to evaluate the impact of two different TPN lipid emulsions on the
      recovery of allograft RES function after orthotopic liver transplantation (OLTx).
      In a prospective, double-blind study, OLTx patients were randomly assigned to two
      treatment groups. Group I ( n=13) received a TPN regimen that included long-chain
      triglycerides (LCT). Group II ( n=9) received a TPN regimen that included a fat
      emulsion consisting of both medium-chain triglycerides (MCT) and LCT. At
      baseline, i.e., on days 2 or 3 after OLTx ( t1), before lipids for TPN were
      started, hepatic RES function was determined using the human serum albumin
      millimicrosphere technique (K-value, 1/min). A second measurement ( t2) was
      obtained after 7 days of TPN, including one of the study's two fat emulsions. The
      mean (+/- SD) K-value (1/min) was 0.48+/-0.16 in the LCT group and 0.55+/-0.28 in
      the MCT/LCT group at t1, and it improved to 0.62+/-0.21 in the LCT group and to
      0.86+/-0.32 in the MCT/LCT group at t2. RES function recovery was significantly
      better in the MCT/LCT group ( P< or = 0.05). MCT/LCT emulsion appears to be the
      TPN fat emulsion of choice after OLTx as it seems to have less impact on hepatic
      RES recovery.

PMID- 12072898
TI  - Normothermic blood perfusion of isolated rabbit kidneys. III. In vitro physiology
      of kidneys after perfusion with Euro-Collins solution or 7.5 M cryoprotectant
      (VS4).
AB  - Cryopreservation of solid organs might be possible using a mixture of cell
      permeable agents, cryoprotectants (CPA), which are designed to completely
      preclude ice crystal formation during cooling to cryogenic temperatures. The
      effects of a specific prototype solution (VS4) were evaluated by normothermic
      blood perfusion in vitro. Rabbit kidneys were divided into three groups:
      untreated controls ( n=7), Euro-Collins (EC)-perfused controls ( n=6) and VS4
      (49%, w/v) CPA-perfused kidneys ( n=7). After a 2-h blood perfusion, five of the
      seven CPA-perfused kidneys developed polyuria (0.21 mlxmin(-1)xg(-1)) relative to
      untreated controls (0.07 mlxmin(-1)xg(-1)) or EC-perfused kidneys (0.06 mlxmin(
      1)xg(-1)), owing to the lower reabsorption of water (34.3%), Na(+) (34.2%) and
      glucose (35.6%). Furthermore, two kidneys were non-functional with virtually no
      urine production. Reduced tubular function was associated with reduced oxygen
      consumption (3.6 versus 2.3 versus 2.0 micromolexmin(-1)xg(-1) for controls, EC-
      and CPA-perfused kidneys, respectively) and increased weight gain (17% versus 20%
      versus 30%, respectively) after blood perfusion. Therefore, the current results
      provide insight into both the physiological effects of VS4 and the limits of
      reversibility of renal pathophysiological states. Our results also indicate that
      in vitro monitoring of oxygen consumption and weight gain of perfused organs
      could be used as predictors of renal function.

PMID- 12072899
TI  - Effects of a single infusion of pamidronate prior to liver transplantation: a
      bone histomorphometric study.
AB  - Osteoporosis is a common and serious complication of solid organ transplantation.
      Effective therapeutic regimens have not been established but evidence that
      increased bone turnover is responsible for bone loss early after transplantation
      provides a rationale for the use of anti-resorptive agents in the peri-operative
      period. We have examined the effects of a single pre-operative infusion of
      pamidronate, 60 mg, on bone remodelling and turnover in a prospective study of 12
      patients, four male and eight female aged 19-61 years, with chronic liver
      disease, who formed a subgroup of a larger randomised controlled single-blind
      study. Iliac-crest biopsies were obtained before and 3 months after liver
      transplantation and histomorphometry performed using image analysis. In untreated
      patients ( n=5) a significant increase in bone formation rate at tissue level was
      demonstrated at 3 months in comparison to pre-operative values (0.035+/-0.013 vs.
      0.161+/-0.12 microm(2)/microm/day; mean +/- SD, P=0.003). In patients treated
      with pamidronate ( n=7) no significant increase in bone formation rate was
      demonstrated at 3 months, although there was a trend towards an increase in
      indices of bone turnover. In this group there was also a significant reduction in
      erosion cavity length (210.4+/-63.8 vs. 179.8+/-67.5 microm; P=0.03) and non
      significant reductions in other indices of erosion cavity size. These results
      indicate that pre-operative administration of pamidronate in patients with
      chronic liver disease prevents, at least in part, the increase in bone turnover
      which occurs in untreated patients after transplantation.

PMID- 12072900
TI  - Expression of fetal isoforms of actin after transplantation injury.
AB  - Trauma and injury to transplanted organs in the early post-transplant period are
      significant factors that affect long-term graft survival. Fetal isoforms of actin
      are integral members of the immediate early gene family and are expressed in
      response to free radical injury. We therefore studied actin gene expression in
      heart transplantation to determine if reperfusion injury activates fetal isoforms
      of actins. Heterotopic cardiac transplantations were performed in mice. mRNA was
      extracted from allo- and isografted hearts as well as from normal hearts and
      spleen. Northern hybridization with actin cDNA to alpha and beta/gamma actin mRNA
      was performed and analyzed by densitometry. The beta/gamma actin gene expression
      in the transplanted hearts was found to be significantly elevated within 48 h
      after transplantation. Analysis of beta/gamma actin gene expression in isografts
      substantiates the possibility of de novo increase in actin expression. Our
      studies demonstrate for the first time that fetal isoforms of actin are induced
      in the allograft heart after transplantation.

PMID- 12072901
TI  - Effector mechanisms in murine allograft rejection: comparison of skin and heart
      grafts in fully allogeneic and minor histocompatibility antigen-mismatched strain
      combinations.
AB  - Cytotoxic T lymphocytes (CTLs) and macrophage-mediated delayed-type
      hypersensitivity (DTH) responses may both mediate allograft rejection.
      Furthermore, although allograft rejection is classically considered a type [22,
      23, 38, 50, 52] 1 cellular immune response, type-2 cytokines can support
      rejection. This study examines whether the immunogenicity of the transplanted
      tissue, as determined by type of tissue (skin versus heart) and degree of
      antigenic mismatch, influences recruitment of these effector mechanisms. Graft
      survival, histological appearance and intragraft gene expression (IL-2, IFN
      gamma, IL-12 p40, IL-4, IL-10, perforin, Fas ligand (Fas L), iNOS and TNF-alpha)
      were compared for fully allogeneic, minor histocompatibility (mHC) antigen
      mismatched and syngeneic skin and heart grafts. We found mRNA characteristic of
      CTLs and DTH responses in fully allogeneic and mHC antigen-mismatched skin and
      heart grafts. Concomitant type-1 and type-2 cytokine gene transcription was seen.
      These findings demonstrate that the tissue grafted and degree of antigenic
      disparity between donor and recipient do not restrict the repertoire of cellular
      immune responses involved in graft rejection. This finding has implications in
      the design of new immunosuppressive strategies for clinical transplantation.

PMID- 12072902
TI  - Coagulation profiles and intraoperative substitution requirements during elective
      piggyback liver transplantation with prophylactic antifibrinolytic therapy.
AB  - During recent years, piggyback liver transplantation (pOLT) with preservation of
      the retrohepatic vena cava has been introduced in adults. The objective of this
      study was to evaluate hemostatic changes associated with this transplantation
      technique. Fifty-seven patients undergoing elective pOLT for endstage liver
      disease were studied. Most significant changes were observed after graft
      reperfusion, when PT showed a 49% decrease and activated partial thromboplastin
      time (aPTT) as well as TT a 2- to 3-fold prolongation. At the same time, factors
      of the extrinsic coagulation pathway (II, V, VII) revealed an overall 50%
      decline. Similar changes were observed for antithrombin III (ATIII) and
      fibrinogen plasma levels. However, only 42% of all patients required
      intraoperative substitution with coagulation components. There was an association
      between preoperative fibrinogen (<1.7 g/dl) and ATIII (<50%) plasma levels and
      the substitution requirement. Multiple linear regression showed a significant
      correlation between preoperative ATIII activity and intraoperative blood loss.
      Despite a marked impairment of hemostasis, pOLT can frequently be performed with
      minimized substitution therapy.

PMID- 12072903
TI  - A prospective randomized controlled study on the efficacy and tolerance of two
      antilymphocytic globulins in the prevention of rejection in first-heart
      transplant recipients.
AB  - The usefulness of induction phase treatment in heart transplantation is a long
      standing debate in the literature. Several centers report good short-term
      survival without such treatment, but no randomized trial addresses this question.
      If induction treatment is to be used, most centers prefer rabbit polyclonal
      antisera to OKT3. However, again, no randomized trial has compared the relative
      efficacy and tolerance of rabbit antisera. Fifty first-heart transplant
      recipients with standard triple immunosuppression were randomized to receive ATG
      Fresenius ( n=24) or Thymoglobulin Merieux ( n=26) as an induction treatment and
      were followed for 1 year. The two groups were well matched for gender, age, pre
      transplant diagnosis and ischemia time. Actuarial survival at 1 year was 87.5% in
      the Fresenius group and 84.6% in the Merieux group (Fisher's exact test; P=1).
      The average number of rejection episodes per patient was comparable in both
      treatment groups (Fresenius: mean=2.63, SD=1.44; Merieux: mean=2.46, SD=2.04).
      Mean time to first rejection was 48.9+/-37.2 days in the Fresenius group versus
      59.6+/-54 days in the Merieux group (Mann-Witney U-test: z=0.77; P=NS). The total
      number of rejections across all patients was also comparable (Fresenius: 63;
      Merieux: 64) as well as the severity of rejection (seven moderate rejections out
      of a total of 63 in the Fresenius group and eight out of 64 in the Merieux
      group). Eighteen Fresenius (75%) and 15 Merieux (58%) patients suffered from at
      least one infection ( P=NS). The tolerance to treatment was excellent in both
      groups. Total lymphocyte count and all subsets of tested lymphocytes decreased
      rapidly after the introduction of either antiserum but was more pronounced and
      persisted for longer in the Merieux group. ATG Fresenius or Thymoglobulin Merieux
      as induction treatments in first-heart transplant recipients treated with
      standard immunosuppression have the same relative efficacy with regard to
      survival, acute rejection or infection rate, and are well tolerated.

PMID- 12072907
TI  - On blood examinations in East African malaria diseases.

PMID- 12072906
TI  - Tissue renin-angiotensin system and end-organ damage.

PMID- 12072908
TI  - Orexins: from neuropeptides to energy homeostasis and sleep/wake regulation.
AB  - The neuropeptides orexin A and orexin B (also called hypocretin 1 and 2) were
      recently discovered by a "reverse pharmacology" approach as ligands for two
      previously orphan G protein coupled receptors: orexin receptors 1 and 2. Neurons
      producing orexins are located exclusively in the lateral hypothalamic area but
      project broadly to various parts of the brain, and they have been implicated in
      the control of energy homeostasis and arousal maintenance. The orexin receptors
      are also broadly expressed in the central nervous system. Murine and canine
      models suggest that defective signaling in the orexin system is responsible for
      the sleep/wake disorder narcolepsy. Although narcoleptic patients rarely have
      genetic defects in the orexin system, they lack these neuropeptides in the brain
      and cerebrospinal fluid, indicating that human narcolepsy is an orexin deficiency
      syndrome in the majority of cases. A connection between sleep/wake regulation and
      energy homeostasis is hypothesized with orexin neuropeptides as a molecular link.

PMID- 12072909
TI  - Embryonic stem cells share immune-privileged features relevant for tolerance
      induction.
AB  - Continuous immunosuppressive treatment allows the majority of transplant
      recipients to accept their donated organ and prevent acute graft rejection.
      However, life-long suppression of the immune system to respond appropriately to
      infectious, fungal, and carcinogenic threats coincides with substantial morbidity
      and mortality for the host. Thus for the past five decades research in the field
      of transplantation medicine has focused on innovative strategies to induce graft
      tolerance to donor alloantigens, a state in which the recipient's lymphocytes
      have learned to accept the foreign organ or tissue as "self" without the need of
      permanent immunosuppression. The fact that individuals of the same species attack
      each other's tissues can be explained with the set of specific antigens,
      designated as major histocompatibility antigens, which are expressed on each cell
      of the body and normally widely differ between nonrelated individuals. According
      to the genetic laws of transplantation, survival of allogeneic grafts is
      correlated with the number of differences among these histocompatibility
      antigens. An important exception to this rule can be observed in pregnant women
      who tolerate their unborn conceptus expressing a full set of nonmaternal antigens
      inherited by the father. The exact mechanisms of immune privilege exhibited by
      embryonic tissue during prenatal development have not yet been characterized in
      each detail. The field of maternofetal immunobiology has lately emerged as a new
      scientific branch in immunology which is gathering useful insights for future
      innovative tolerance strategies to prevent allogeneic graft rejection.

PMID- 12072910
TI  - Molecular components of transient outward potassium current in cultured neonatal
      rat ventricular myocytes.
AB  - We have previously reported that K(v1.4), K(v4.2), and K(v4.3) mRNAs are present
      in adult and neonatal rat ventricular myocytes, and that transient outward
      potassium current (I(to)) recovers from inactivation with a slow (I(to,s)) and a
      fast (I(to,f)) time course. This study was designed to determine the molecular
      correlates of I(to,s) and I(to,f) in cultured neonatal rat ventricular myocytes
      (NRVM) employing dominant-negative adenoviral infections to manipulate the
      function of endogenous I(to)-encoding K+ channels. Western blot data from
      cultured NRVM showed that K(v1.4), K(v4.2), and K(v4.3) channel proteins are
      present in these myocytes. The biphasic recovery from inactivation of I(to) in
      control GFP-infected myocytes demonstrated equal contribution of I(to,s) and
      I(to,f) in NRVM. Infection of cultured NRVM with adenoviruses expressing full
      length K(v1.4) or K(v4.2) genes generated currents with recovery from
      inactivation kinetics similar to native I(to,s) and I(to,f) in GFP-infected
      myocytes, respectively. Overexpression of dominant-negative truncated K(v1.4)
      transgene (K(v1.4)N) caused a 51% reduction in I(to), selectively removing the
      slowly recovering I(to,s). Overexpression of dominant-negative K(v4.2)N reduced
      I(to) by 53% and eliminated the fast-recovering I(to,f). Our results establish
      that, in neonatal rat ventricular myocytes, the shaker K(v1) family (probably
      K(v1.4) and/or K(v1.7)) underlies I(to,s), and that the shal K(v4) family
      (probably K(v4.2) and K(v4.3)) is responsible for I(to,f).

PMID- 12072911
TI  - Reduced hypertension-induced end-organ damage in mice lacking cardiac and renal
      angiotensinogen synthesis.
AB  - Hypertension-induced damage of kidney and heart is of major clinical relevance,
      but its pathophysiology is only partially understood. As there is considerable
      evidence for involvement of angiotensin II, we generated a new mouse model by
      breeding angiotensinogen (AOGEN) deficient mice with transgenic animals
      expressing the rat AOGEN gene only in brain and liver. This genetic manipulation
      overcame the hypotension of AOGEN-deficient mice and even caused hypertension
      indistinguishable in its extent from the parent transgenic mice with an intact
      endogenous AOGEN gene. In contrast to normal mice, however, crossbred animals
      lacked detectable expression of AOGEN in kidney and heart. As a consequence they
      showed markedly reduced cardiac hypertrophy and fibrosis. Furthermore,
      hypertension-induced alterations in kidney histology and function were less
      pronounced in crossbred mice than in equally hypertensive animals expressing
      AOGEN locally. The dysmorphogenesis observed in kidneys from AOGEN-deficient mice
      was absent in mice expressing this gene only in liver and brain. Our results
      support an important role of local AOGEN expression in hypertension-induced end
      organ damage but not in the development of the kidney.

PMID- 12072912
TI  - Clinically relevant aminoglycosides can suppress disease-associated premature
      stop mutations in the IDUA and P53 cDNAs in a mammalian translation system.
AB  - Recent studies have suggested that the use of aminoglycosides to suppress disease
      causing nonsense mutations may be a promising new therapy for a large number of
      genetic diseases. However, gentamicin is currently the only clinically relevant
      aminoglycoside shown to suppress premature stop mutations in a mammalian system.
      We compared the ability of the clinically approved aminoglycosides gentamicin,
      tobramycin, and amikacin to suppress premature stop mutations. Using readthrough
      reporter constructs as well as mammalian cDNAs containing naturally occurring
      premature stop mutations, we found that each of these aminoglycosides can
      suppress many premature stop mutations in a context-dependent manner in a
      mammalian translation system. Our results indicate that the tetranucleotide
      termination signal (the stop codon and the nucleotide 3' of the stop codon) is
      the primary determinant for aminoglycoside-mediated suppression. The levels of
      termination suppression achieved by tobramycin were substantially lower than
      those observed with gentamicin. In contrast, amikacin stimulated suppression in a
      manner that was generally similar to gentamicin. Amikacin produced higher levels
      of readthrough than gentamicin at some contexts, demonstrating a unique pattern
      of context dependence. Experiments with mammalian cDNAs confirmed these results
      and demonstrated that these aminoglycosides can also suppress disease-associated
      premature stop mutations previously identified in the IDUA gene (responsible for
      the lysosomal storage disease mucopolysaccharidosis I) and the P53 gene
      (associated with many forms of cancer). Taken together, these results suggest
      that amikacin represents an alternative to gentamicin for suppression therapy in
      certain contexts, thus providing a means of optimizing the efficacy of
      aminoglycoside-mediated suppression of premature stop mutations.

PMID- 12072913
TI  - Induction of acute phase response genes in keratinocytes following exposure to
      oligodeoxynucleotides.
AB  - Keratinocytes have the ability to take up oligodeoxynucleotides (ODN) and plasmid
      DNA probably by receptor-mediated endocytosis. Despite the use of DNA for
      antisense and gene therapy little is known about the regulation of genes
      following exposure to nucleic acids. To systematically identify gene regulation
      in keratinocytes upon exposure to ODN we screened human cytokine DNA arrays
      containing 383 different genes and found interleukin (IL) 1alpha, IL-1beta,
      integrin-beta(1), alpha-tubulin, and follistatin highly induced, while most genes
      were unaffected. The time course and concentration dependence for IL-1alpha and
      follistatin expression were analyzed by standard northern blot technique. ODN of
      different length and sequence induced comparable amounts of IL-1alpha and
      follistatin. Their induction was independent of negative charge and of several
      proinflammatory compounds such as lipopolysaccharides, IL-1beta, and interferon
      gamma but was partly inhibited by activin A. In summary, our study revealed
      several genes of the acute phase protein family that are induced in a non
      sequence-specific manner following the exposure of normal human keratinocytes to
      ODN. Therefore it is tempting to speculate that upon internalization ODN bind to
      an intracellular receptor (e.g., Toll-like receptor 9) which mediates signaling.

PMID- 12072915
TI  - Parvalbumin 3 is an abundant Ca2+ buffer in hair cells.
AB  - Ca2+ signaling serves distinct purposes in different parts of a hair cell. The
      Ca2+ concentration in stereocilia regulates adaptation and, through rapid
      transduction-channel reclosure, underlies amplification of mechanical signals. In
      presynaptic active zones, Ca2+ mediates the exocytotic release of afferent
      neurotransmitter. At efferent synapses, Ca2+ activates the K+ channels that
      dominate the inhibitory postsynaptic potential. A copious supply of diffusible
      protein buffer isolates the three signals by restricting the spread of free Ca2+
      and limiting the duration of its action. Using cDNA subtraction and a gene
      expression assay based on in situ hybridization, we detected abundant expression
      of mRNAs encoding the Ca2+ buffer parvalbumin 3 in bullfrog saccular and chicken
      cochlear hair cells. We cloned cDNAs encoding this protein from the corresponding
      inner-ear libraries and raised antisera against recombinant bullfrog parvalbumin
      3. Immunohistochemical labeling indicated that parvalbumin 3 is a prominent Ca2+
      binding protein in the compact, cylindrical hair cells of the bullfrog's
      sacculus, and occurs as well in the narrow, peanut-shaped hair cells of that
      organ. Using quantitative Western blot analysis, we ascertained that the
      concentration of parvalbumin 3 in saccular hair cells is approximately 3 mM.
      Parvalbumin 3 is therefore a significant mobile Ca2+ buffer, and perhaps the
      dominant buffer, in many types of hair cell. Moreover, parvalbumin 3 provides an
      early marker for developing hair cells in the frog, chicken, and zebrafish.

PMID- 12072916
TI  - In silico analyses of mouse inner-ear transcripts.
AB  - The development and function of the inner ear is complex requiring the correct
      and coordinated expression of many genes. The recent progress in the analyses of
      the human and other genomes has provided tools for identification of genes
      involved in hearing. As more and more nucleotide sequence information
      accumulates, experimental methods of molecular biology are rapidly being
      supplemented, and partially supplanted, by computational methods. In this study
      we present comprehensive in silico analyses of a cDNA library representing almost
      1600 transcripts isolated from mouse inner ear. By mining the public databases we
      were able to rapidly and efficiently identify numerous transcripts likely to have
      a specific role in the auditory or vestibular function of the inner ear. Analyses
      revealed about 600 known genes and almost 100 inner-ear specific transcripts.
      Almost 50 of these are candidate genes for hearing impairment based on their
      chromosomal localization and inner-ear expression pattern. We describe a powerful
      approach to identify novel genes associated with hearing and vestibular function,
      further increasing our understanding of the molecular biology of the inner ear.

PMID- 12072918
TI  - Treatment of severe Candida infections in high-risk patients in Germany:
      consensus formed by a panel of interdisciplinary investigators.
AB  - Now that modern medicine can provide increasing chances of cure to patients with
      formerly incurable disorders, therapy-related complications play the key role in
      outcome. Thus, among opportunistic infections, severe candidiasis remains a
      challenge. A multidisciplinary panel of 20 investigators was formed to find a
      consensus on antifungal strategies for various underlying conditions in
      neutropenic and non-neutropenic patients. To record their preferences, the
      investigators used an anonymous voting system. Among antifungal agents,
      fluconazole emerged as the major alternative to the classic amphotericin B, being
      therapeutically at least equivalent but clearly less toxic. Factors that restrict
      the use of fluconazole include pretreatment with azoles, involvement of resistant
      species like Candida krusei, and an inability to exclude aspergillosis.
      Flucytosine can be reasonably combined with both amphotericin B and fluconazole.
      Within the limited antifungal armamentarium, amphotericin B lipid formulations
      and itraconazole also appear useful and require further investigation. The
      general consensus of the group is that antifungal agents should be administered
      at sufficient dosages, rather early, and often empirically.

PMID- 12072919
TI  - Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of
      Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with
      advanced HIV infection.
AB  - The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine
      combination supplemented with 15 mg folinic acid twice a week as primary
      prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis
      was evaluated in 106 patients infected with the human immunodeficiency virus. All
      patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study
      entry. Efficacy in this single-arm open-label prospective study was analyzed on
      an as-treated basis. No patient received highly active antiretroviral treatment,
      including protease inhibitors or non-nucleoside reverse transcriptase inhibitors,
      while on study medication. PCP developed in four patients, one of whom had been
      noncompliant. No PCP episode occurred in the first year. Probabilities of freedom
      from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after
      36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies,
      one noncompliant patient developed toxoplasmic encephalitis after 24 months.
      Allergic reactions were observed in 18 (17%) patients and resulted in permanent
      discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued
      prophylaxis despite progressive hypersensitivity reactions developed a serious
      adverse reaction (Stevens-Johnson syndrome). The median survival of study
      participants was 29 months, with relentless progression of AIDS accounting for
      most deaths. The prophylaxis regimen studied appeared safe and effective for
      primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events
      can likely be prevented by discontinuation of prophylaxis at the time allergic
      reactions are noted. Rechallenge frequently results in tolerance. Efficacy and
      safety compare favorably with previously studied regimens. This simple
      prophylactic regimen may provide a convenient alternative for patients failing or
      intolerant to approved regimens.

PMID- 12072921
TI  - Increasing incidence of gonorrhea in Israel associated with countrywide
      dissemination of a ciprofloxacin-resistant strain.
AB  - The annual incidence of gonorrhea in Israel has sharply increased during the past
      2 years. At the end of 1999, high-level ciprofloxacin-resistant strains of
      Neisseria gonorrhoeae (MIC90, > or =32 mcg/ml) also exhibiting decreased
      susceptibility to penicillin and tetracycline were isolated for the first time in
      southern Israel, as well as in other regions of the country. The incidence of
      male gonococcal urethritis in the south increased in a 1.5-year period from
      3/100,000 to 12/100,000 ( P<0.05) in correlation with increased isolation of
      ciprofloxacin-resistant organisms. A marked increase in the incidence of
      gonorrhea was also encountered in Jerusalem, where ciprofloxacin resistance
      affected 54.5% of the isolates in 2000. Pulsed-field gel electrophoresis typing
      of gonococci from different areas of Israel indicated that all of the
      ciprofloxacin-resistant isolates belonged to identical or related strains. Since
      fluoroquinolone-resistant gonococci may emerge and disseminate extensively over a
      short period of time, continuous surveillance of antibiotic susceptibility among
      gonococcal isolates should be performed to guide empiric therapy.

PMID- 12072920
TI  - Usefulness of sputum culture for diagnosis of bacterial pneumonia in HIV-infected
      patients.
AB  - The use of sputum culture in immunocompetent patients with community-acquired
      pneumonia is controversial. The usefulness of this technique in HIV-infected
      patients has not been evaluated. A prospective, observational, multicenter,
      hospital-based study of bacterial community-acquired pneumonia was carried out to
      analyze the value of sputum culture in HIV-infected patients. Only good-quality
      sputum samples were cultured. Altogether, 355 cases of bacterial community
      acquired pneumonia were included. An etiological diagnosis was obtained in 190
      (53.5%) cases. Sputum was cultured in 313 (88.1%) cases, being diagnostic in 108
      (34.5%). The microorganism identified in sputum culture was the same as that
      identified in sterile samples in 26 of 27 (96.3%) cases in which both cultures
      were diagnostic. The microbiologic findings in sputum and bronchoscopic cultures
      were concordant in seven of eight (87.5%) cases in which both were positive.
      These results suggest that sputum culture is a useful technique, given its
      availability and ease of performance and its good correlation with culture of
      sterile samples.

PMID- 12072922
TI  - Differential fluorescent staining method for detection of bacteria in blood
      cultures, cerebrospinal fluid and other clinical specimens.
AB  - The aim of this study was to evaluate a differential staining method to
      distinguish gram-positive from gram-negative bacteria in fluorescence. The method
      is based on two fluorochromes, one acting in the wavelength of red, i.e. the
      acridine orange, and another acting in the wavelength of green, i.e. the
      fluorescein. With this method, gram-positive bacteria appear yellow and gram
      negative bacteria appear green. In view of the importance of a rapid aetiological
      diagnosis in cases of septicaemia, the differential staining method in
      fluorescence was compared with Gram stain for the detection of bacteria in blood.
      Of 5,820 blood cultures entered into the study and identified by the Bactec 9120
      fluorescent series instrument (Becton Dickinson Europe, France), 774 were
      positive. Of the 774 positive cultures, 689 yielded only a single organism. The
      differential staining method in fluorescence detected 626 of the 689 cultures,
      while Gram stain detected 468. On the basis of these results, the sensitivity of
      the differential staining method in fluorescence was 90.9%, while that of Gram
      stain was 67.9%. The difference between the two methods was statistically
      significant ( P<0.001). The differential fluorescent staining method was more
      sensitive than Gram stain in the detection of bacteria in blood cultures during
      the incubation period. This technique provides a rapid, simple and highly
      sensitive staining method that can be used in conjunction with subculture
      methods. Whereas subculture requires an incubation period of 18-24 h, the
      fluorescent staining technique can detect bacteria on the same day that smears
      are prepared and examined. The differential fluorescent staining method was also
      evaluated for its ability to detect microorganisms in cerebrospinal fluid and
      other clinical specimens. The microorganisms were easily detected, even when
      bacterial counts in the specimens were low.

PMID- 12072923
TI  - In vitro evaluation of the antibacterial activity of three different central
      venous catheters against gram-positive bacteria.
AB  - The aim of this study was to evaluate the activity of three different catheters
      against Staphylococcus aureus ATCC 29213 and the slime-producing Staphylococcus
      epidermidis ATCC 35984 (RP62A). Three central venous catheters were evaluated:
      one impregnated with silver sulfadiazine-chlorhexidine, one to which
      minocycline/rifampin is bonded and a novel one into which silver, platinum and
      carbon are incorporated. A nonantiseptic catheter was used as the control
      catheter. One-centimeter trisected pieces of catheter were immersed in phosphate
      buffered saline (0.01 mol/l) with 0.25% dextrose and incubated. On days 1, 3, 7,
      14 and 21, a 1 ml standardized inoculum was added for 30 min and then replaced
      with phosphate-buffered saline with 0.25% dextrose. One-third of the samples were
      immediately sonicated and plated to determine bacterial adherence. The remaining
      segments were incubated for 4 and 24 h to determine the persistence of bacterial
      adherence. Bacterial adherence to the catheters impregnated with silver
      sulfadiazine-chlorhexidine was reduced 91-98% for the first 7 days. Adherence of
      Staphylococcus aureus to catheters into which silver, platinum and carbon are
      incorporated was reduced 70% on day 1 and 35% on day 3. Adherence to
      minocycline/rifampin-bonded catheters was quite variable. There was an 85.6-99.8%
      reduction in the persistence of bacterial adherence to the three catheters
      compared to controls. Bacteriostatic and bactericidal studies indicated that the
      effluents from the catheters impregnated with silver sulfadiazine-chlorhexidine
      were bactericidal, while effluents from the minocycline/rifampin-bonded catheters
      were bacteriostatic. The antibacterial activity of the effluents from catheters
      impregnated with silver sulfadiazine-chlorhexidine dissipated by day 7, while the
      activity of effluents from the minocycline/rifampin-bonded catheters continued to
      show activity at day 21. No measurable antibacterial activity was detected in the
      effluents of the catheters into which silver, platinum and carbon are
      incorporated. These data suggest that catheters coated with
      antibiotic/antibacterial agents and the novel catheters that incorporate
      antiseptic agents have different activities against initial bacterial adherence.
      All of them, however, effectively prevent bacterial colonization by gram-positive
      bacteria.

PMID- 12072924
TI  - High mortality related with Staphylococcus aureus bacteremia after liver
      transplantation.
AB  - The aim of the present study was to analyze the characteristics of bacteremia
      occurring in liver-transplant patients in Andalusia, Spain, during the 1990s. At
      the three participating hospitals, 405 liver transplantations were performed
      during the study period, and 119 bacteremic episodes were observed following 91
      of them (22.4%, 29.4 episodes/100 liver transplants). Gram-positive organisms
      were the predominant bacteria isolated in cases of early-onset bacteremia (70.7%,
      P=0.04). The most common sources of bacteremia were the abdomen (33.6%) and
      intravascular catheters (22.7%), but frequently the source of bacteremia was
      unknown (31.9%). Mortality at 30 days was 21%. Isolation of Staphylococcus aureus
      was the only independent risk factor for mortality (relative risk, 3.13; 95%
      confidence interval, 1.3-7.5; P=0.01). These results indicate that control
      measures are required in order to reduce the incidence of gram-positive
      bacteremia and catheter-related infection in this patient population. The
      observed etiology must be considered when empirical antimicrobial therapy is
      indicated while awaiting blood-culture results.

PMID- 12072925
TI  - Streptococcus pneumoniae-infected aneurysm extending from a persistent lobar
      pneumonia: case report and review of the literature.
AB  - Presented here is the case of a 63-year-old patient with a Streptococcus
      pneumoniae-infected aneurysm extending from a persistent lobar pneumonia of the
      left lung into the thoracic aorta. The patient was successfully treated with
      surgery and high-dose penicillin, and he remained well at 6-month follow-up. A
      review of the English-language literature over the past 25 years revealed 22
      cases of mycotic or infected aortic aneurysms due to Streptococcus pneumoniae;
      however, none of these cases resulted in a positive outcome for the patient. The
      characteristics of these cases are discussed.

PMID- 12072926
TI  - Identification of viridans streptococcal species causing bacterial meningitis in
      adults in Taiwan.
AB  - In order to determine the species responsible for viridans-group streptococcal
      meningitis in adults in Taiwan, seven cases of culture-proven meningitis due to
      these organisms were studied. The cases were all identified at the Chang Gung
      Memorial Hospital-Kaohsiung over a period of 3 years, and they accounted for 9%
      (7/78) of all cases of culture-proven bacterial meningitis occurring in adults
      during this period. Of the seven viridans streptococci isolates recovered,
      Streptococcus constellatus accounted for four, Streptococcus anginosus for two,
      and Streptococcus oralis for one. Thus, it appears that streptococci of the
      milleri group are the most common species causing bacterial meningitis in adults
      in Taiwan. The tendency for these organisms to cause invasive central nervous
      system infections in adults should not be overlooked when these species are
      recovered from cerebrospinal fluid specimens.

PMID- 12072927
TI  - Seroprevalence of human granulocytic ehrlichiosis infection in Belgium.
AB  - In order to determine the prevalence of human granulocytic ehrlichiosis (HGE) in
      Belgium, the sera of 216 patients previously diagnosed with Borrelia burgdorferi
      infection were analysed for possible coinfection with the agent of HGE. For this
      purpose, an indirect immunofluorescence assay was applied, and positive results
      were confirmed by Western blot using a 44-kilodalton recombinant protein (rP44)
      specific for the agent of HGE. Sixteen of the 216 (7.4%) sera tested were
      positive for the HGE agent using indirect immunofluorescence assay, and seven
      (3%) of them were confirmed positive by Western blot. These data suggest the
      agent for HGE is present in Belgium and may cause coinfection in patients
      infected with Borrelia burgdorferi, as has been reported in the USA and elsewhere
      in Europe. This is the first report documenting the identification of this agent
      in Belgium.

PMID- 12072928
TI  - Vibrio alginolyticus as the cause of pleural empyema and bacteremia in an
      immunocompromised patient.

PMID- 12072929
TI  - Comparative study of two anti-HCV screening tests in a large genotyped population
      of Brazilian dialysis patients.

PMID- 12072931
TI  - Rifampin resistance in Streptococcus pyogenes.

PMID- 12072930
TI  - Broth medium for microdilution susceptibility tests of fluconazole and
      voriconazole.

PMID- 12072932
TI  - New screening medium for detection and identification of methicillin/oxacillin
      resistant Staphylococcus aureus for nosocomial surveillance.

PMID- 12072933
TI  - Evaluation of a latex agglutination test for detection of immunoglobulin M (IgM)
      and IgG antibodies to Mycoplasma pneumoniae.

PMID- 12072934
TI  - Promising role of 18-F-fluoro-D-deoxyglucose positron emission tomography in
      clinical infectious diseases.
AB  - 18-F-fluoro-D-deoxyglucose positron emission tomography (FDG PET) has become an
      established imaging tool in clinical oncology, cardiology and neurology and is
      now entering the field of clinical infectious diseases. The purpose of this
      article is to review the currently available, albeit limited, literature on FDG
      PET in the diagnosis of various infections and fever of unknown origin. Those
      indications for which FDG PET offers added value over more available techniques
      like labelled leucocyte scanning, gallium scanning and magnetic resonance imaging
      are especially highlighted. FDG PET seems to have an incremental value in the
      assessment of chronic osteomyelitis, especially in the axial skeleton, as well as
      in the diagnostic workup of fever of unknown origin and HIV complications. Cost
      effectiveness studies are needed to define its place in the current diagnostic
      strategies of these pathologies.

PMID- 12072935
TI  - Anthrax in adults and children: a review of 132 cases in Turkey.
AB  - In this retrospective study, 132 cases of anthrax observed in a Turkish hospital
      over a 14-year period (October 1986 to October 2000) were evaluated with respect
      to clinical features, therapy, and outcome. The results show that anthrax is a
      disease of significance in the Eastern Anatolian region of Turkey. Preventive
      measures such as education of the population and vaccination of animals against
      anthrax would reduce the incidence of the disease.

PMID- 12072936
TI  - Prognostic evaluation of bacteremia and fungemia in patients with acquired
      immunodeficiency syndrome.
AB  - The incidence of bacterial infections in general and of bacteremia in particular
      is high among patients with acquired immunodeficiency syndrome (AIDS). The
      factors influencing the prognosis of bacteremia in these patients are not well
      known. In order to better define those factors associated with a poor prognosis,
      all episodes of bacteremia or fungemia in patients with AIDS who were
      hospitalized in four general hospitals between 1 September 1987 and 31 December
      1996 were studied prospectively. Among 1,390 patients diagnosed with AIDS, 238
      (17.1%) developed 274 episodes of bacteremia or fungemia. Mortality related to
      bacteremia was 21.3%. Variables associated with high mortality were fungemia
      (odds ratio [OR], 6.19; 95% confidence interval [CI], 1.99 - 19.28), hypotension
      (OR, 19.65; 95%CI, 7.42 - 52.07), inappropriate antimicrobial treatment (OR,
      16.94; 95%CI, 4.92 - 58.32), and unknown origin of bacteremia (OR, 3.93; 95%CI,
      1.58 - 9.76). The mortality rate among patients with at least one of these
      factors was 46.7%, whereas in patients without any of these factors, the rate was
      4.9% ( P < 0.001). Bacteremic episodes of unknown origin were significantly more
      frequently associated with community acquisition ( P = 0.001), inappropriate
      antimicrobial treatment ( P = 0.04), and etiology by gram-negative microorganisms
      or fungi ( P < 0.001) and were significantly less frequently associated with the
      presence of a previous intravenous catheter ( P = 0.004), resulting in peculiar
      etiologic and epidemiological profiles. The factors that influence the outcome of
      AIDS patients who develop bacteremia are sometimes avoidable or known during the
      first days after admission. Therefore, knowledge about these factors could
      improve the prognosis of bloodstream infections in this population.

PMID- 12072937
TI  - Proteolytic activity of Staphylococcus aureus strains isolated from the colonized
      skin of patients with acute-phase atopic dermatitis.
AB  - Staphylococcus aureus strains isolated from the colonized skin lesions of 26
      patients with acute-phase atopic dermatitis were reported to produce various
      extracellular proteolytic enzymes. Using the skim-milk-agar culture plating
      method, it was shown that 97% of the strains (65 of 67 examined) produced
      proteolytic activity, with 61% (42 strains) producing activity comparable to that
      of the proteolytically hyperactive reference strain Staphylococcus aureus V8.
      This observation was confirmed by azocasein degradation with culture
      supernatants, which indicated that 91% of the strains produced extracellular
      proteinases and 43% exceeded the 2% activity threshold of the reference strain.
      Control strains were isolated from the nose vestibules of 18 healthy carriers;
      the proteolytic activity of these strains never exceeded 2.5% of the activity of
      the reference strain. In 54% of the patients examined ( n=14), the activity of
      the strains was higher than that determined for the isolates from the control
      group. The combined use of assays incorporating azocasein and a synthetic
      chromogenic substrate, N-CBZ-Phe-Leu-Glu- pNA, showed that two staphylococcal
      enzymes, Staphylococcus aureus metalloproteinase (SAMP) and Staphylococcus aureus
      serine proteinase (SASP), contributed to the total proteolytic activity released
      by the strains examined. The contribution of each of the two enzymes varied
      greatly between different isolates. The undamaged skin of the patients was not
      colonized with Staphylococcus aureus. The presence of several strains with
      atypical proteinase characteristics was also reported, suggesting the possible
      involvement of enzymes other than serine- and metallo-proteinases in the
      proteolytic activity of Staphylococcus aureus. Taken together, the results of the
      study imply that staphylococcal proteinases may contribute to the pathogenicity
      of atopic dermatitis.

PMID- 12072938
TI  - Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective
      analysis of 111 cases.
AB  - The clinical and epidemiological characteristics of 111 consecutive cases of
      visceral leishmaniasis identified from 1980 to 2000 in a Sicilian pediatric
      hospital were analyzed retrospectively. The mean age of the patients was 1.7
      years. All children were HIV negative, but 15% were severely malnourished. Fever
      and splenomegaly were present in all cases and hepatomegaly in 101 (90.1%) cases.
      Thrombocytopenia and anemia were both observed in 78 (70.2%) cases and leukopenia
      in 47 (42.3%) cases. A bone marrow aspirate was obtained in all cases; Leishmania
      amastigotes were detected in 89 (80.2%) cases. Initial treatment consisted of
      meglumine antimoniate in 99 (89.2%) patients and amphotericin B in 12 (10.8%)
      patients. Only two children treated with meglumine antimoniate relapsed. The
      findings highlight the differences between the cases of visceral leishmaniasis
      observed in the Mediterranean basin and those observed in other regions. The use
      of the term "Mediterranean visceral leishmaniasis", rather than the term "kala
      azar", is proposed for cases observed in the Mediterranean area.

PMID- 12072939
TI  - Comparative evaluation of two commercial chromogenic media for detection and
      presumptive identification of urinary tract pathogens.
AB  - The performance of two commercial chromogenic media for the isolation and
      presumptive identification of urinary tract pathogens, the CPS ID2 (bioMerieux,
      France) and the CHROMagar Orientation (BBL Becton Dickinson, USA), was evaluated
      and compared with that of cystine-lactose-electrolyte-deficient agar and tryptic
      soy agar with 5% sheep blood. The detection, determination of bacterial counts,
      and presumptive identification of bacteria causing urinary tract infections were
      evaluated in 3,000 urine specimens. The two chromogenic media showed excellent
      correlation with the standard media for the detection and the bacterial count of
      urinary pathogens. The Escherichia coli strains produced the expected colour on
      the CHROMagar Orientation and the CPS ID2 media in 99% and 90% of the cases,
      respectively. The Klebsiella-Enterobacter-Citrobacter and the Proteus-Morganella
      Providencia groups were easily identified on both chromogenic media, but further
      biochemical tests were needed to differentiate them to a species level. Both
      media enabled the differentiation, with varying degrees of difficulty, of
      Pseudomonas spp. strains from members of the family Enterobacteriaceae. All
      isolates of Enterococcus spp. were correctly identified and were easily
      distinguished from the Streptococcus agalactiae isolates. Staphylococcus
      saprophyticus isolates were easy to identify only on the CHROMagar Orientation
      medium. No substantial difference was observed when comparing the results of the
      susceptibility tests, which were performed according to the standardized disk
      diffusion method as described by the National Committee for Clinical Laboratory
      Standards, for colonies recovered from the blood agar versus those recovered from
      the chromogenic media. In conclusion, the CPS ID2 and CHROMagar Orientation media
      enabled excellent detection, count determination, and presumptive identification
      of urinary pathogens, both in pure and mixed cultures, and reliable and accurate
      antimicrobial susceptibility testing directly from primary isolates. Moreover,
      these media allowed a remarkable reduction in the workload and a significant
      savings of time. On the basis of their performance, these media can replace the
      standard primary plating media used in the routine diagnosis of urinary tract
      infections.

PMID- 12072940
TI  - Analysis of risk factors for bacteremia in children with nontyphoidal Salmonella
      gastroenteritis.
AB  - To identify the risk factors for Salmonella bacteremia in infants and children
      with Salmonella gastroenteritis, a retrospective study of a 10-year period was
      conducted to evaluate 456 infants and children with culture-proven nontyphoidal
      Salmonella infection. Salmonella typhimurium was the most common isolate found.
      Among the 257 patients with gastroenteritis who had a concomitant blood culture
      performed, 50 exhibited bacteremia. Statistically significant differences were
      noted between patients with gastroenteritis and bacteremia and those without
      bacteremia in duration of fever > or = 5 days ( P < 0.001; OR, 5.6; 95% CI, 2.6 -
      12.1) and infection with group D1 Salmonella ( P < 0.001; OR, 6.5; 95% CI, 2.5 -
      16.9) after adjustment for multivariate analysis. Of the 320 Salmonella strains
      that were serotyped, Salmonella panama was shown to be strongly associated with
      bacteremia ( P<0.001) in children with gastroenteritis. In summary, in children
      with nontyphoidal Salmonella gastroenteritis, prolonged fever lasting 5 days or
      more and infection with a specific Salmonella serotype were risk factors closely
      associated with development of bacteremia.

PMID- 12072941
TI  - Two cases of fungemia due to Candida lusitaniae and a literature review.
AB  - Reported here are two cases of candidemia caused by Candida lusitaniae that
      occurred in two immunocompromised patients at Hospital Universitario "La Fe" in
      Valencia, Spain. Case 1 involved a low-birth-weight premature infant with
      congenital nephrotic syndrome who was successfully treated with amphotericin B,
      and case 2 involved a 50-year old woman with a high-grade malignancy lymphoma who
      succumbed to the infection. Antifungal susceptibility testing of the Candida
      lusitaniae isolates recovered from both patients revealed sensitivity to
      amphotericin, 5-flucytosine and fluconazole. Results are presented and discussed
      together with a comprehensive review of the literature, covering all previously
      reported cases of fungemia caused by this emerging pathogen.

PMID- 12072942
TI  - Chlamydia pneumoniae infection among healthy children and children hospitalised
      with pneumonia in Greece.
AB  - Chlamydia pneumoniae has been recognized as a cause of respiratory tract
      infection in humans, and its prevalence has been shown to vary among different
      age groups and populations. The prevalence of Chlamydia pneumoniae antibody was
      determined by serological investigation in 343 healthy children and in 77
      children consecutively hospitalised for pneumonia in southwestern Greece. Seventy
      eight (22.7%) healthy children had IgG Chlamydia pneumoniae titers > or =1/8. The
      prevalence of Chlamydia pneumoniae antibody in the age groups 6 months-5 years, 6
      9 years and 10-15 years was 7.9%, 11.4% and 36%, respectively. One child
      hospitalised for pneumonia had serological results consistent with acute
      Chlamydia pneumoniae infection. The results of the present study suggest a low
      prevalence of Chlamydia pneumoniae antibody among preschoolers in Greece,
      followed by a steep rise in children 10-15 years of age. Chlamydia pneumoniae is
      not a common etiologic agent of childhood pneumonia requiring hospitalisation.

PMID- 12072943
TI  - Tula virus infection associated with fever and exanthema after a wild rodent
      bite.
AB  - Reported here is the first case of human acute infection with Tula virus, which
      occurred in a 12-year-old boy in Switzerland. This hantavirus had been considered
      apathogenic to humans, and in Switzerland only TULV-genome sequences have been
      demonstrated in wild rodents to date. In this case, paronychia, fever and
      exanthema occurred after the patient was bitten by a wild rodent, indicating an
      unusual route of hantavirus transmission. Thus, Tula virus infection should be
      taken into account in patients with appropriate clinical symptoms and contact
      with rodents.

PMID- 12072945
TI  - Prevalence of genotypic resistance in untreated HIV patients in Spain.
AB  - The aims of this retrospective study were to assess the prevalence of primary
      genotypic resistance to antiretroviral drugs in untreated HIV patients in Spain
      using the line probe assay and to determine its possible relationship to several
      epidemiological variables. The global prevalence of primary resistance was 12.5%.
      Primary mutations in the reverse transcriptase gene were found in two (2.2%)
      samples: M41L, K70R and M184 V were found in one sample and K70R in another.
      Primary mutations in the protease gene were detected in 12% of cases; V82A was
      the mutation most frequently detected (11/12, 91.6%). No statistical significance
      was found for any of the epidemiological variables studied. In conclusion, the
      prevalence of primary resistance detected is similar to that found by other
      authors.

PMID- 12072946
TI  - Reliability of cord formation in BACTEC 12B/13A media for presumptive
      identification of Mycobacterium tuberculosis complex in laboratories with a high
      prevalence of Mycobacterium tuberculosis.
AB  - A total of 1208 positive BACTEC vials were examined for the presence or absence
      of serpentine cording. A very high (92.9%) rate of laboratory prevalence was
      obtained for Mycobacterium tuberculosis complex. The sensitivity, specificity,
      positive and negative predictive values of this test were 92.7%, 95.3%, 99.6% and
      50.0%, respectively. It was concluded that testing cord formation in laboratories
      that have a high prevalence of Mycobacterium tuberculosis complex is an
      exceptionally reliable method for preliminary reporting of cording-positive
      cases; however, for cording-negative cases, preliminary reports based solely on
      cord formation are not reliable. It was also observed that the length of the
      incubation period has a significant effect on cord formation. Incubation periods
      of 4 days or less are not sufficient to determine noncording in smears prepared
      from positive BACTEC vials.

PMID- 12072944
TI  - Serological evidence of acute infection with the Chlamydia-like microorganism
      Simkania negevensis (Z) in acute exacerbation of chronic obstructive pulmonary
      disease.
AB  - The aims of this study were twofold: (i) to test for possible associations
      between serological evidence of acute Simkania negevensis (Sn) infection and
      acute exacerbation of chronic obstructive pulmonary disease and (ii) to examine
      the prevalence of past infections with Sn in patients with chronic obstructive
      pulmonary disease. In 120 patients (63%) there was serological evidence of past
      infection with Sn, which was not significantly different from the rate in a
      control population. In five hospitalizations serological evidence existed of
      acute infection with Sn around the time of the exacerbation of chronic
      obstructive pulmonary disease. In four of these cases, there was serological
      evidence of acute infection with at least one other respiratory pathogen. It is
      concluded that Sn can be associated serologically with exacerbation of chronic
      obstructive pulmonary disease, in most cases together with other respiratory
      pathogens. The implications of these findings should be investigated further.

PMID- 12072947
TI  - A case of lung transplantation following Mycoplasma pneumoniae infection.
AB  - Reported here is a case of severe necrotizing pneumonia following Mycoplasma
      pneumoniae infection that occurred in a 55-year-old man. The histological changes
      of lung parenchyma included granulomas and bronchiolitis obliterans. Mycoplasma
      infection was diagnosed by repeated antibody determination (complement fixation
      test) and confirmed using the polymerase chain reaction to detect the pathogen
      from a tracheal aspirate. Prior to this episode of pneumonia, the patient had
      been healthy, except for Reiter's disease that had been diagnosed 18 years
      previously. In addition to severe pulmonary involvement, the patient developed
      rhabdomyolysis with subsequent acute renal failure, Stevens-Johnson syndrome,
      biochemical pancreatitis, severe anemia, and an effusion of the right knee.
      Contrary to the symptoms of pulmonary disease, all of the extrapulmonary
      manifestations except anemia were transient. Due to persistent respiratory
      insufficiency and long-term failure to wean the patient from a respirator, a lung
      transplantation was performed. Five weeks after transplantation the patient died
      as a result of intrapulmonary hemorrhage. To the best of our knowledge, this is
      the first report of pneumonia due to Mycoplasma pneumoniae leading to lung
      transplantation. Furthermore, the multiple extrapulmonary manifestations in this
      case make it exceptional.

PMID- 12072948
TI  - Spontaneous bacterial peritonitis due to Listeria monocytogenes in a patient with
      primary pulmonary hypertension.

PMID- 12072949
TI  - Epidemic Acinetobacter baumannii strain with MRSA-like behaviour carried by
      healthcare staff.

PMID- 12072950
TI  - In vitro activity of the active metabolite of prulifloxacin (AF 3013) compared
      with six other fluoroquinolones.

PMID- 12072952
TI  - Expression of xylanase enzymes from thermophilic microorganisms in fungal hosts.
AB  - Bulk production of xylanases from thermophilic microorganisms is a prerequisite
      for their use in industrial processes. As effective secretors of gene products,
      fungal expression systems provide a promising, industrially relevant alternative
      to bacteria for heterologous enzyme production. We are currently developing the
      yeast Kluyveromyces lactis and the filamentous fungus Trichoderma reesei for the
      extracellular production of thermophilic enzymes for the pulp and paper industry.
      The K. lactis system has been tested with two thermophilic xylanases and secretes
      gram amounts of largely pure xylanase A from Dictyoglomus thermophilum in
      chemostat culture. The T. reesei expression system involves the use of the
      cellobiohydrolase I (CBHI) promoter and gene fusions for the secretion of
      heterologous thermostable xylanases of both bacterial and fungal origin. We have
      reconstructed the AT-rich xynB gene of Dictyoglomus thermophilum according to
      Trichoderma codon preferences and demonstrated a dramatic increase in expression.
      A heterologous fungal gene, Humicola grisea xyn2, could be expressed without
      codon modification. Initial amounts of the XYN2 protein were of a gram per liter
      range in shake-flask cultivations, and the gene product was correctly processed
      by the heterologous host. Comparison of the expression of three thermophilic
      heterologous microbial xylanases in T. reesei demonstrates the need for
      addressing each case individually.

PMID- 12072953
TI  - Molecular characterization of fervidolysin, a subtilisin-like serine protease
      from the thermophilic bacterium Fervidobacterium pennivorans.
AB  - The fls gene encoding fervidolysin, a keratin-degrading proteolytic enzyme from
      the thermophilic bacterium Fervidobacterium pennivorans, was isolated using
      degenerate primers combined with Southern hybridization and inverse polymerase
      chain reaction. Further sequence characterization demonstrated that the 2.1-kb
      fls gene encoded a 699-amino-acid preproenzyme showing high homology with the
      subtilisin family of the serine proteases. It was cloned into a pET9d vector,
      without its signal sequence, and expressed in Escherichia coli. The
      heterologously produced fervidolysin was purified by heat incubation followed by
      ion exchange chromatography and emerged in the soluble fraction as three distinct
      protein bands, as judged from sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Amino-terminal-sequence analysis of these bands and their
      comparison with that determined from biochemically purified keratinase and its
      predicted protein sequence, identified them as a 73-kDa fervidolysin precursor, a
      58-kDa mature fervidolysin, and a 14-kDa fervidolysin propeptide. Using site
      directed mutagenesis, the active-site histidine residue at position 79 was
      replaced by an alanine residue. The resulting fervidolysin showed a single
      protein band corresponding in size to the 73-kDa fervidolysin precursor,
      indicating that its proteolytic cleavage resulted from an autoproteolytic
      process. Knowledge-based modeling experiments showed a distinctive binding region
      for subtilases, in which binding of the propeptide could take place prior to
      autoproteolysis. Assays using keratin and other proteinaceous substrates did not
      display fervidolysin activity, perhaps because of the tight binding of the
      propeptide in the substrate-binding site, where it could then function as an
      inhibitor.

PMID- 12072954
TI  - Molecular identification of alkaliphilic and halotolerant strain Bacillus sp. FTU
      as Bacillus pseudofirmus FTU.
AB  - The systematic position of the alkaliphilic and halotolerant strain Bacillus sp.
      FTU was refined in view of the comprehensive taxonomic revision of the group of
      alkaliphilic and alkalitolerant Bacillus strains. Sequence analysis of almost the
      entire 16S rRNA gene of Bacillus sp. FTU revealed 99.8% homology with two
      Bacillus pseudofirmus strains. Subsequent DNA-DNA hybridization analysis
      confirmed the close relationship of Bacillus sp. FTU with the type strain of B.
      pseudofirmus (the level of homology reached 86%). Results of physiological and
      biochemical characterizations relevant for the group clearly underlined the
      positioning of strain FTU within this species. It is therefore concluded that
      Bacillus sp. FTU represents a strain of the alkaliphilic species B. pseudofirmus
      and is to be renamed as B. pseudofirmus FTU. The phylogeny of different Bacillus
      species is discussed using N-terminal sequence homologies of some caa (3)-type
      oxidase subunits.

PMID- 12072955
TI  - Acidophiles of saline water at thermal vents of Vulcano, Italy.
AB  - DNA was extracted from samples taken from close to acidic hydrothermal vents on
      shore of the Aeolian Island of Vulcano (Italy). RNA gene sequences were amplified
      by PCR, cloned, and sequenced. A sequence with an origin in samples at 35 degrees
      and 45 degrees C corresponded to that of a novel Acidithiobacillus species that
      was isolated from water close to the vents. Novel, iron-oxidizing mesophilic
      acidophiles were isolated through enrichment cultures with ferrous iron but were
      not represented in the clone banks of environmental rDNA. These acidophiles were
      related to Thiobacillus prosperus, which was isolated previously from Vulcano.
      The archaeal sequences that comprised a clone bank representing a high
      temperature sample (75 degrees C) corresponded to those of Acidianus brierleyi
      and of thermophiles previously isolated from Vulcano, Thermoplasma volcanium and
      Acidianus infernus.

PMID- 12072956
TI  - Comparative study of the thermostabilizing properties of mannosylglycerate and
      other compatible solutes on model enzymes.
AB  - The protection of mannosylglycerate, at 0.5 M concentration, against heat
      inactivation of the model enzyme lactate dehydrogenase (LDH) was compared to that
      exerted by other compatible solutes, namely, trehalose, ectoine, hydroxyectoine,
      di- myo-inositol phosphate, diglycerol phosphate, and mannosylglyceramide.
      Mannosylglycerate and hydroxyectoine were the best stabilizers of the enzyme and
      showed comparable protective effects. Diglycerol phosphate, trehalose, and
      mannosylglyceramide protected the enzyme to a lower extent. Ectoine conferred no
      protection, and di- myo-inositol phosphate had a strong destabilizing effect. The
      superior ability of mannosylglycerate to prevent LDH inactivation was accompanied
      by a higher efficiency in preventing LDH aggregation induced by heat stress.
      Moreover, mannosylglycerate induced an increase of 4.5 degrees C in the melting
      temperature of LDH, whereas the same molar concentration of trehalose caused an
      increase of only 2.2 degrees C. The effectiveness of mannosylglycerate in
      protecting LDH was also compared to that of other chemically related compounds:
      mannose, methyl-mannoside, potassium glycerate, glucosylglycerol, glycerol, and
      glucose. Mannosylglycerate conferred the highest protection, but glucosylglycerol
      and potassium glycerate were very efficient; glucose exerted a low degree of
      protection, glycerol and methyl-mannoside had no significant effect, and mannose
      caused destabilization. Mannosylglycerate was also a good thermoprotectant of
      glucose oxidase from Aspergillus niger, an enzyme with a net charge opposite to
      that of LDH under the working conditions. Given the superior performance of
      mannosylglycerate as a thermoprotectant of enzyme activity in vitro, it is
      conceivable that it also fulfills a protein thermoprotective function in vivo.

PMID- 12072957
TI  - Amino acid composition of bulk protein and salt relationships of selected enzymes
      of Salinibacter ruber, an extremely halophilic bacterium.
AB  - The extremely halophilic bacterium Salinibacter ruber was previously shown to
      have a high intracellular potassium content, comparable to that of halophilic
      Archaea of the family Halobacteriaceae. The amino acid composition of its bulk
      protein showed a high content of acidic amino acids, a low abundance of basic
      amino acids, a low content of hydrophobic amino acids, and a high abundance of
      serine. We tested the level of four cytoplasmic enzymatic activities at different
      KCl and NaCl concentrations. Nicotinamide adenine dinucleotide (NAD)-dependent
      isocitrate dehydrogenase functioned optimally at 0.5-2 M KCl, with rates of 60%
      of the optimum value at 3.3 M. NaCl provided less activation: 70% of the optimum
      rates in KCl were found at 0.2-1.2 M NaCl, and above 3 M NaCl, activity was low.
      We also detected nicotinamide adenine dinucleotide phosphate (NADP)-dependent
      isocitrate activity, which remained approximately constant between 0-3.2 M NaCl
      and increased with increasing KCl concentration. NAD-dependent malate
      dehydrogenase functioned best in the absence of salt, but rates as high as 25% of
      the optimal values were measured in 3-3.5 M KCl or NaCl. NAD-dependent glutamate
      dehydrogenase, assayed by the reductive amination of 2-oxoglutarate, showed low
      activity in the absence of salt. NaCl was stimulatory with optimum activity at 3
      3.5 M. However, no activity was found above 2.5 M KCl. Although the four
      activities examined all function at high salt concentrations, the behavior of
      individual enzymes toward salt varied considerably. The results presented show
      that Salinibacter enzymes are adapted to function in the presence of high salt
      concentrations.

PMID- 12072958
TI  - The periplasmic space in Thermus thermophilus: evidence from a regulation
      defective S-layer mutant overexpressing an alkaline phosphatase.
AB  - The presence of a periplasmic space within the cell envelope of Thermus
      thermophilus was analyzed in a mutant (HB8(Delta)UTR1) defective in the
      regulation of its S-layer (surface crystalline layer). This mutant forms round
      multicellular bodies (MBs) surrounded by a common envelope as the culture
      approaches the stationary phase. Confocal microscopy revealed that the origin of
      the MBs is the progressive detachment of the external layers coupled with the
      accumulation of NH(2)-containing material between the external envelopes and the
      peptidoglycan. A specific pattern of proteins was found as soluble components of
      the intercellular space of the MBs by a single fractionation procedure,
      suggesting that they are periplasmic-like components. To demonstrate this, we
      cloned a gene ( phoA) from T. thermophilus HB8 encoding a signal peptide-wearing
      alkaline phosphatase (AP), and engineered it to be overexpressed in the mutant
      from a shuttle vector. Most of the AP activity (>80%) was found as a soluble
      component of the MBs' intercellular fraction. All these data indicate that
      Thermus thermophilus actually has a periplasmic space which is functionally
      similar to that of Proteobacteria. The potential application of the
      HB8(Delta)UTR1 mutant for the overexpression of periplasmic thermophilic proteins
      is discussed.

PMID- 12072959
TI  - A novel subtilisin-like serine protease from Thermoanaerobacter yonseiensis KB-1:
      its cloning, expression, and biochemical properties.
AB  - A gene, tayI, encoding a novel subtilisin-like protease, designated thermicin,
      from the extremely thermophilic bacterium Thermoanaerobacter yonseiensis KB-1
      (DSM 13777) was cloned by using a sequence tag containing the consensus sequence
      of proteases. The gene consisted of 1,239 nucleotides, and the deduced amino acid
      sequence indicated that it is a preproenzyme with a 311-residue mature protein
      composed of canonical catalytic residues (Asp29, His64, and Ser252). Thermicin
      was overproduced in E. coli as a fusion protein with a histidine tag and purified
      by nickel nitrilotriacetic acid affinity chromatography. Thermicin from E. coli
      showed maximum proteolytic activity at 92.5 degrees C and pH 9.0, and its half
      life was 30 h at 80 degrees C. In order to determine cleavage specificity,
      thermicin was incubated with insulin beta chain, and the resulting peptides were
      analyzed by matrix assisted laser desorption/ionization-time of flight mass
      spectrometry. The carboxyl group side of the Val12, Leu15,17, Gly23, and Pro28
      residues was cleaved. Thermicin is well known to hydrolyze Gly- and Pro-rich
      collagens. The K (m) and k (cat)/ K (m) values of thermicin for the hydrolysis of
      the synthetic substrate L-Gly-Pro- p-nitroaniline were 54.16 microM and 142.05
      (10(5) s(-1) M(-1)), respectively, at 92.5 degrees C and pH 9.0. Amino acid
      sequence comparison and phylogenetic analysis indicated that this enzyme belongs
      to a new subgroup with respect to its molecular evolution, when compared with
      previously characterized subtilisins. This result indicates that thermicin is a
      novel enzyme different from other thermostable proteases.

PMID- 12072960
TI  - A new type of dihydroorotate dehydrogenase, type 1S, from the thermoacidophilic
      archaeon Sulfolobus solfataricus.
AB  - Dihydroorotate dehydrogenase (DHOD) (EC 1.3.3.1) from the thermoacidophilic
      archaeon Sulfolobus solfataricus P2 (DSM 1617) was partially purified 3,158-fold,
      characterized, and the encoding genes identified. Based on enzymological as well
      as phylogenetic methods, dihydroorotate dehydrogenase from S. solfataricus
      (DHODS) represents a new type of DHOD, type 1S. Furthermore, it is unable to use
      any of the (type-specific) natural electron acceptors employed by all other
      presently known DHODs. DHODS shows optimal activity at 70 degrees C in the pH
      range 7-8.5. It is capable of using ferricyanide, 2,6-dichlorophenolindophenol
      (DCIP), Q(0), and molecular oxygen as electron acceptor. Kinetic studies
      employing ferricyanide indicate a two-site ping-pong mechanism with K(M) values
      of 44.2+/-1.9 microM for the substrate dihydroorotate and 344+/-21 microM for the
      electron acceptor ferricyanide, as well as competitive product inhibition with a
      K(i) of 23.7+/-3.4 microM for the product orotate (OA). The specific activity, as
      determined from a partially purified sample, is approximately 20 micromol mg(-1)
      min(-1). DHODS is a heteromeric enzyme comprising a catalytic subunit encoded by
      pyrD (291 aa; MW=31.1 kDa) and an electron acceptor subunit (208 aa; MW=23.6
      kDa), encoded by orf1. DHODS employs a serine as catalytic base, which is unique
      for a cytosolic DHOD. To our knowledge, this work represents not only the first
      study on an archaeal DHOD but the first on a nonmesophilic DHOD as well.

PMID- 12072961
TI  - Planococcus antarcticus and Planococcus psychrophilus spp. nov. isolated from
      cyanobacterial mat samples collected from ponds in Antarctica.
AB  - Thirteen orange-pigmented bacteria associated with cyanobacterial mat samples
      collected from four different lakes in McMurdo, Antarctica, were isolated. Twelve
      of the isolates, which were coccoid in shape, were very similar and possessed all
      the characteristics of the genus Planococcus and represented a new species, which
      was assigned the name Planococcus antarcticus sp. nov. (CMS 26or(T)). Apart from
      the phenotypic differences, P. antarcticus differed from all reported species of
      Planococcus by more than 2.5% at the 16S rRNA gene sequence level. In addition,
      at the DNA-DNA hybridization level, it exhibited very little similarity either
      with P. mcmeekinii (30%-35%), P. okeanokoites (26%-29%), or CMS 53or(T) (15%
      25%), the three species with which it is closely related at the rRNA gene
      sequence level (2.5%-2.9%). P. antarcticus also showed only 2.5% difference in
      its 16S rRNA gene sequence compared with the P. alkanoclasticus sequence. But it
      was distinctly different from P. alkanoclasticus, which exists only as rods, is
      mesophilic and phosphatase positive, can hydrolyze starch, cannot utilize
      succinate, glutamate, or glucose, and cannot acidify glucose. Most important, P.
      antarcticus and P. alkanoclasticus varied distinctly in their fatty acid
      composition in that C(15:0), C(15:1), C(16:0), iso-C(16:1), and C(17:0) were
      present only in P. antarcticus but absent in P. alkanoclasticus. CMS 53or(T), the
      thirteenth isolate, was also identified as a new species of Planococcus and was
      assigned the name Planococcus psychrophilus sp. nov. This species was distinctly
      different from all the reported species, including the new species P.
      antarcticus, with respect to a number of phenotypic characteristics. At the 16S
      rRNA gene sequence level, it was closely related to P. okeanokoites (98.1%) and
      P. mcmeekinii (98%), but with respect to the DNA-DNA hybridization, the
      similarity was only 35%-36%. The type strain of P. antarcticus is CMS 26or(T)
      (MTCC 3854; DSM 14505), and that of P. psychrophilus is CMS 530r(T) (MTCC 3812;
      DSM 14507).

PMID- 12072962
TI  - Human kidney diamine oxidase: heterologous expression, purification, and
      characterization.
AB  - Human kidney diamine oxidase has been overexpressed as a secreted enzyme under
      the control of a metallothionein promoter in Drosophila S2 cell culture. This
      represents the first heterologous overexpression and purification of a
      catalytically active, recombinant mammalian copper-containing amine oxidase. A
      rapid and highly efficient purification protocol using chromatography on heparin
      affinity, hydroxyapatite, and gel filtration media allows for the recovery of
      large quantities of the recombinant enzyme, which is judged to be greater than
      98% homogenous by SDS/PAGE. The availability of large quantities of highly
      purified enzyme makes it now possible to investigate the spectroscopic,
      mechanistic, functional, and structural properties of this human enzyme at the
      molecular level. Visible absorption, circular dichroism, electron paramagnetic
      resonance, and resonance Raman spectroscopic results are presented. The
      recombinant enzyme contains the cofactors 2,4,5-trihydroxyphenylalaninequinone
      and copper at stoichiometries of up to 1.1 and 1.5 mol per mol homodimer,
      respectively. In addition, tightly bound and stoichiometric calcium ions were
      identified and proposed to occupy a second metal-binding site. The apparent
      molecular weight of the recombinant protein, determined by analytical
      ultracentrifugation, suggests 20-26% glycosylation by weight. Detailed kinetic
      studies indicate the preferred substrates (k(cat)/K(M)) of human diamine oxidase
      are, in order, histamine, 1-methylhistamine, and putrescine, with K(M) values of
      2.8, 3.4, and 20 microM, respectively. These results, demonstrating the substrate
      preference for histamine and 1-methylhistamine, were unanticipated given the
      available literature. The pH dependence of k(cat) for putrescine oxidation gives
      two apparent p K(a) values at 6.0 and 8.2. Tissue-specific expression of the
      human diamine oxidase gene was investigated using an mRNA array. The relevance of
      this work to earlier work and the suggested physiological roles of the human
      enzyme are discussed.

PMID- 12072963
TI  - Dynamic docking and electron transfer between myoglobin and cytochrome b(5).
AB  - The interaction of trypsin-digested bovine cytochrome b(5) (cyt b(5)) with horse
      heart myoglobin (Mb) and the interprotein electron transfer (ET) between these
      redox partners have been studied to gain better understanding of ET processes
      between weakly bound protein partners. The bimolecular rate constant ( k(2)) for
      photo-induced ET between zinc-substituted Mb (ZnMb) and cyt b(5) decreases with
      increasing ionic strength, consistent with the predominantly electrostatic
      character of this complex. The formation of a protein-protein complex has been
      confirmed and the binding affinities of metMb and ZnMb for cyt b(5) have been
      measured by two techniques: (1)H NMR titrations at pH 6.0 give binding constants
      of K(a) approximately (1.0+/-0.1)x10(3) M(-1) for metMb and K(a) approximately
      (0.75+/-0.1)x10(3) M(-1) for ZnMb; isothermal calorimetry gives K(a)
      approximately (0.35+/-0.1)x10(3) M(-1) for ZnMb. Brownian dynamic (BD)
      simulations show that cyt b(5) binds over a broad surface of Mb that includes its
      heme edge. The experimental results are described in terms of a dynamic docking
      model which proposes that Mb binds cyt b(5) in a large ensemble of protein
      binding conformations, not one or a few dominant ones, but that only a small
      subset are ET reactive. Aided by the BD simulations, this model explains why k(2)
      decreases with increasing pH: increasing pH not only weakens the binding affinity
      but also reduces the number of binding conformations with high ET reactivity.

PMID- 12072964
TI  - Unusual features for zirconium(IV) binding to human serum transferrin.
AB  - Human serum apotransferrin (hTF) binds to Zr(IV) slowly in the presence of
      nitrilotriacetate (NTA), citrate or ethylenediaminetetraacetate (EDTA) as donor
      ligands. For Zr(NTA)(2)(2-) as donor, equilibrium was reached in ca. 2 h (pH 7.4,
      298 K, 10 mM Hepes, 5 mM bicarbonate) and full loading of the N- and C-lobe sites
      was achievable to give Zr(2)-hTF. (13)C NMR data suggest that carbonate can bind
      as a synergistic anion. (1)H and 2D [(1)H,(13)C] (using epsilon-[(13)C]Met-hTF)
      NMR studies show that there is little lobe-selectively in the order of Zr(IV)
      uptake. Fe(III) displaced Zr(IV) from the C-lobe of Zr(2)-hTF first, followed by
      the N-lobe. However, in the presence of a large excess of NTA, Zr(IV) binds to
      the N-lobe of holo-hTF (Fe(2)-hTF) first followed by the C-lobe. The (1)H and
      (13)C NMR chemical shift changes for epsilon-[(13)CH(3)] of Met464, which is
      close to the C-lobe site, are quite distinct from those observed previously for
      Al(III), Fe(III), Ti(IV), Ga(III) and Bi(III) binding to hTF, suggesting that
      Zr(IV) binding may not induce lobe closure [as observed previously for Hf(IV)].
      This may affect receptor recognition and play a role in the different biological
      behaviour of Zr(IV) compared to Ti(IV).

PMID- 12072965
TI  - Mechanistic studies of the astacin-like Serratia metalloendopeptidase serralysin:
      highly active (>2000%) Co(II) and Cu(II) derivatives for further corroboration of
      a "metallotriad" mechanism.
AB  - Serralysin is a bacterial Zn-endopeptidase which has been considered a virulence
      factor to cause tissue damage and anaphylactic response. It contains a
      coordinated Tyr that is unique to the astacin-like Zn enzymes. The coordinated
      Tyr has been proposed to play an important role in the action of this
      endopeptidase family. Several metal-substituted derivatives of serralysin
      (including Mn2+, Co2+, Ni2+, Cu2+, and Cd2+ derivatives) are found to exhibit
      significant activities. Particularly, the Co- and Cu-substituted derivatives
      exhibit much higher activities than the native serralysin toward the hydrolysis
      of the tripeptide mimic benzoyl-Arg- p-nitroanilide, i.e., 35 and 49 times higher
      in k(cat) and 33 and 26 times in k(cat)/ K(m), respectively. Such remarkably
      higher activities of metal-substituted derivatives, especially the Cu derivative,
      than that of the native Zn enzyme are rare in the literature, reflecting the
      uniqueness of this enzyme among all Zn enzymes. The significantly different
      k(cat) yet similar K(m) values among the several metal derivatives suggests that
      the metal center is involved in catalysis, but not necessarily in the binding of
      the substrate, whereas the dramatically different inhibition constants for Arg
      hydroxamate binding to the metal-substituted derivatives indicates direct binding
      of this inhibitor to the metal center. The activity-pH profiles of serralysin and
      its Co2+ and Cu2+ derivatives and the optical-pH profile of Cu-serralysin have
      been obtained, in which the decrease in activity at higher pH values was found to
      be associated with a dramatic increase in the Tyr-to-Cu2+ charge transfer
      transitions. This observation suggests that the binding of Tyr216 to the metal is
      inhibitory. A metal-centered mechanism is proposed for serralysin catalysis based
      on the results presented here, in which the detachment of the coordinated Tyr and
      formation of a H-bond with the transition-state complex are considered essential
      for the stabilization of the transition state.

PMID- 12072966
TI  - A distinct Cu(4)-thiolate cluster of human metallothionein-3 is located in the N
      terminal domain.
AB  - Metallothionein-3 (MT-3), also known as neuronal growth inhibitory factor, is a
      metalloprotein expressed almost exclusively in the brain. Isolated MT-3 contains
      four Cu(I) and three Zn(II) ions organized in homometallic metal-thiolate
      clusters located in two independent protein domains. In this work a Cu(I) binding
      to metal-free MT-3 has been studied, aiming at the better understanding of the
      domain specificity for this metal ion. The cluster formation was followed by
      electronic absorption, circular dichroism, and by luminescence spectroscopy at
      room temperature and 77 K. The stepwise incorporation of Cu(I) into recombinant
      human apo-MT-3 revealed the cooperative formation of two Cu(4)S(9) clusters in
      succession, formed in both protein domains, i.e. Cu(4)- and Cu(8)-MT-3. Further
      binding of four Cu(I) caused an expansion of these Cu(I) cores, leading to fully
      metal-loaded Cu(12)-MT-3 containing Cu(6)S(9) and Cu(6)S(11) clusters in the beta
      and alpha-domains of the protein, respectively. The location of the
      preferentially formed Cu(4) cluster in the protein was established by
      immunochemistry. Using domain-specific antibodies, in combination with limited
      tryptic digestion of a partially metal-occupied Cu(4)-MT-3, we could demonstrate
      that the Cu(4)S(9) cluster is located in the N-terminal beta-domain of the
      protein that contains a total of nine cysteine ligands.

PMID- 12072967
TI  - A paramagnetic probe to localize residues next to carboxylates on protein
      surfaces.
AB  - It is shown that the paramagnetic properties of lanthanides can be exploited to
      obtain information on specific parts of a protein surface. Owing to the high
      affinity of coordinatively unsaturated lanthanide complexes for oxygen donors,
      carboxylate groups can be used as preferential targets for the interaction. The
      DO3A ligand is particularly useful in these studies, as it coordinates
      lanthanides in a heptadentate fashion, leaving two sites available for exogenous
      donors. A solution of a (15)N-labeled sample protein, calbindin D(9k) (75
      residues), was titrated with up to 200% of Gd(III)-DO3A complex, and an inversion
      recovery (15)N-(1)H HSQC experiment was used to measure the paramagnetic
      contributions to the longitudinal relaxation rates of the amide protons.
      Relaxation data were used as distance constraints to estimate the number of
      interacting complexes and the occupancies of their binding sites. Four
      preferential interaction sites on the protein surface are found. Inspection of
      the various carboxylate side chains on the surface of the protein indicates that
      Gd(III)-DO3A interacts preferentially with carboxylate-rich regions, rather than
      with isolated carboxylates, suggesting the possibility of chelation of one
      Gd(III)-DO3A molecule by two carboxylate groups. Gd(III)-DO3A is thus a valuable
      semi-selective probe for clusters of negative charges on the protein surface.

PMID- 12072968
TI  - Molecular characterization of Bacillus pasteurii UreE, a metal-binding chaperone
      for the assembly of the urease active site.
AB  - The present study describes the cloning, isolation, and thorough biochemical
      characterization of UreE from Bacillus pasteurii, a novel protein putatively
      involved in the transport of Ni in the urease assembly process. A DNA fragment of
      the B. pasteurii urease operon, containing all four accessory genes (ureE, ureF,
      ureG, and ureD) required for the incorporation of Ni ions into the active site of
      urease, was cloned, sequenced, and analyzed. B. pasteurii ureE was cloned, and
      the UreE protein (BpUreE) was over-expressed and purified to homogeneity. The
      identity of the recombinant protein was determined by N- and C-terminal
      sequencing and by mass spectrometry. BpUreE has a chain length of 147 amino
      acids, and features a p I value of 4.7. As isolated, BpUreE contains one Zn(II)
      ion per dimer, while no Ni(II) is present, as shown by mass spectrometry and
      atomic absorption spectroscopy. BpUreE behaves as a dimer independently of the
      presence of Zn(II), as shown by gel filtration and mass spectrometry.
      Paramagnetic NMR spectroscopy on concentrated (2 mM) UreE solutions reveals a one
      Ni atom per tetramer stoichiometry, with the Ni(II) ion bound to histidines in an
      octahedral coordination environment. BpUreE has a high sequence similarity with
      UreE proteins isolated from different biological sources, while no sequence
      homology is observed with proteins belonging to different classes. In particular,
      BpUreE is most similar to UreE from Bacillus halodurans (55% identity). A
      multiple sequence alignment reveals the presence of four strictly conserved
      residues (Leu55, Gly97, Asn98, His100; BpUreE numbering), in addition to position
      115, conservatively occupied by an Asp or a Glu residue. Several secondary
      structure elements, including a betaalphabetabetaalphabeta "ferredoxin-like"
      motif, are highly conserved throughout the UreE sequences.

PMID- 12072969
TI  - Density functional calculation of p K(a) values and redox potentials in the
      bovine Rieske iron-sulfur protein.
AB  - The redox potential of the Rieske iron-sulfur protein depends on pH. It has been
      proposed that the histidines coordinating one of the irons are responsible for
      this pH dependence, but an experimental proof for this proposal is still lacking.
      In this work, we present a density functional/continuum electrostatics
      calculation of the p K(a) values of the histidines in the Rieske iron-sulfur
      center. The calculated apparent p K(a) values are 6.9 and 8.8 in the oxidized
      state, which are in good agreement with the corresponding experimental values of
      7.5 and 9.2 and the measured pH dependence of the redox potential. Neither of
      these two p K(a) values can, however, be assigned to only one of the histidines.
      We find that both histidines titrate over a wide pH range in the oxidized state.
      Reduction of the iron-sulfur center shifts the p K(a) values to 11.3 and 12.8,
      thus above 10.0 as found experimentally. The results provide a complete picture
      of the coupling of proton and electron binding, showing strongly cooperative
      binding of protons at electrode potentials near the redox midpoint potential of
      the cluster. The potential biological function of the low p K(a) value of the
      histidines and the shift upon reduction are briefly discussed.

PMID- 12072970
TI  - Hard X-ray microprobe studies of chromium(VI)-treated V79 Chinese hamster lung
      cells: intracellular mapping of the biotransformation products of a chromium
      carcinogen.
AB  - The uptake of carcinogenic and mutagenic Cr compounds and the intracellular
      distribution of their biotransformation products in V79 Chinese hamster lung
      cells were studied by synchrotron-radiation-induced X-ray emission (SRIXE). SRIXE
      analysis was performed on whole cells that had been treated with either Cr(III)
      or Cr(V) 1,10-phenanthroline complexes, or Cr(VI). The high spatial resolution
      (0.3 microm) and elemental sensitivity (~10(-15) g Cr/cell) of the technique
      provided detailed maps of Cr and other cellular elements in thin sections
      prepared from Cr(VI)-treated cells. The Cr carcinogen concentrated in P-rich
      regions corresponding to the nucleus, as well as other areas of the cell that are
      likely to correspond to organelles. This is the first study that has enabled the
      determination of the localization of the biotransformation products of Cr(VI)
      carcinogens in a target lung cell.

PMID- 12072972
TI  - Superoxide reductase: fact or fiction?
AB  - It was recently proposed that anaerobic microorganisms contain a new pathway for
      detoxification of reactive oxygen species. This is centered around a novel
      mononuclear iron-containing enzyme, superoxide reductase (SOR), which catalyzes
      the reduction, rather than the dismutation, of superoxide to hydrogen peroxide. A
      surprisingly large amount of relevant data has accumulated in the two years or so
      since the proposal was made. Herein we address the questions: to what extent has
      the pathway been validated, and what fundamental issues have yet to be answered
      in considering the response of anaerobes to reactive oxygen species? The evidence
      for superoxide reduction by SOR is now overwhelming and comes from a variety of
      anaerobic and microaerophilic species. Moreover, the available spectroscopic and
      structural information provide a convincing case that the catalytic Fe site of
      SOR is structurally and electronically tuned to mediate superoxide reduction
      rather than oxidation. Kinetic analyses also support the original proposal of
      NAD(P)H, via rubredoxin and NAD(P)H:rubredoxin oxidoreductase, as the source of
      reductant. What is still to be determined is the fate of the peroxide generated
      by the SOR reaction. In particular, the role of otherwise well-characterized
      proteins like rubrerythrin, NADH peroxidase, and rubredoxin:oxygen oxidoreductase
      in "anaerobic" oxygen metabolism has yet to be established.

PMID- 12072973
TI  - The mechanism(s) of superoxide reduction by superoxide reductases in vitro and in
      vivo.
AB  - Exposure of obligately anaerobic bacteria and archaea to transiently aerobic or
      micro-aerobic growth habitats requires that these microorganisms protect against
      oxidative stress resulting from adventitious dioxygen reduction. Superoxide
      reductases (SORs), which catalyze reduction of superoxide to hydrogen peroxide,
      have been identified as one component of a novel oxidative stress protection
      system in anaerobic bacteria and archaea. SORs contain a unique non-heme
      [Fe(His)(4)(Cys)] active site. This Commentary addresses the mechanism of
      superoxide reduction catalyzed by this unique active site in SORs both in vitro
      and in vivo.

PMID- 12072974
TI  - What biological purpose is served by superoxide reductase?
AB  - The recent discovery that oxygen-sensitive microbes contain superoxide reductase
      (SOR) activity was unexpected, but it conforms with the idea that all organisms
      periodically encounter oxygen and must defend themselves against reactive oxygen
      species. While it remains formally possible that the SOR activity of these
      enzymes is adventitious, most physical, distributional, and genetic data suggest
      that their role is indeed to scavenge superoxide. An interesting challenge, then,
      is to identify the presumptive advantage that superoxide reduction provides to
      these organisms relative to superoxide dismutation. Some potential benefits of
      superoxide reduction have been proposed; these and several others are considered
      here.

PMID- 12072975
TI  - What is the ultimate fate of superoxide anion in vivo?
AB  - For three decades, oxidative stress and the role of reactive oxygen species in
      biology have been extensively studied. Recently, a new interest in these areas
      has emerged with the discovery of superoxide reductases, a family of familiar
      bacterial metalloenzymes whose heretofore unknown function has now been
      apparently revealed. In a series of experiments utilizing genetic, molecular
      biological, and biochemical methods, these enzymes have been shown to be
      physiologically competent at removing superoxide. The role of these enzymes and
      their biological relationship to the well-known superoxide dismutases is
      discussed.

PMID- 12072976
TI  - Superoxide scavenging by neelaredoxin: dismutation and reduction activities in
      anaerobes.
AB  - A superfamily of mononuclear iron proteins, originally named desulfoferrodoxin
      and neelaredoxin, has been identified by in vivo and in vitro studies as
      scavengers of the superoxide anion radical. These proteins, whose genes are
      present in all the so-far known genomes from anaerobes and in the microaerophilic
      pathogen Treponema pallidum, show not only a considerable amino acid sequence
      identity but, most importantly, a common active iron site, Fe[His(4)CysGlu], in
      the oxidized state which loses the glutamate ligand in the reduced form. The
      experimental evidence for the activity of these proteins as superoxide dismutases
      or as donor:superoxide oxidoreductases is discussed in this Commentary, giving
      particular emphasis to the neelaredoxin from the hyperthermophilic archaeon
      Archaeoglobus fulgidus.

PMID- 12072980
TI  - Laccases and other polyphenol oxidases in ecto- and ericoid mycorrhizal fungi.
AB  - Polyphenol oxidases are known to be produced by a range of ectomycorrhizal (ECM)
      and ericoid mycorrhizal fungi. These enzymes include laccase (EC 1.10.3.2),
      catechol oxidase (EC 1.10.3.1) and tyrosinase (EC 1.14.18.1), between which there
      exists considerable overlap in substrate affinities. In this review we consider
      the nature and function of these enzymes, along with the difficulties associated
      with assigning precise enzymatic descriptions. The evidence for production of
      laccase and other polyphenol oxidases by ECM and ericoid mycorrhizal fungi is
      critically assessed and their potential significance to the mycorrhizal symbioses
      discussed.

PMID- 12072981
TI  - Mycorrhizal plants of traditionally managed boreal grasslands in Norway.
AB  - This paper reports on the mycorrhizal status of 82 plant species growing in
      traditionally managed grasslands in three different locations in the boreal and
      boreo-nemoral vegetation zone in the eastern part of Norway. Seventy-four species
      were found to have arbuscular mycorrhiza (AM). To our knowledge, we report AM for
      the first time in Achillea ptarmica, Ajuga pyramidalis, Alchemilla glaucescens,
      Carex brunnescens, Carex pallescens, Crepis praemorsa, Hieracium lactucella,
      Rumex longifolius, Scorzonera humilis, Trifolium aureum and Trifolium spadiceum.
      The rare and threatened species Arnica montana, S. humilis, C. praemorsa,
      Gentianella campestris, Parnassia palustris, T. aureum and T. spadiceum, all
      confined to grasslands, were found to possess AM fungi.

PMID- 12072982
TI  - Magnesium ions alleviate the negative effect of manganese on Glomus claroideum
      BEG23.
AB  - The phytotoxicity of excessive levels of manganese (Mn), an essential
      micronutrient, can be alleviated significantly by a high supply of magnesium (Mg)
      ions to plants. A similar interaction of these two elements in the development of
      arbuscular mycorrhizal (AM) fungi has been verified in two experimental systems.
      In in vitro experiments, an outgrowth of hyphae from excised, surface-disinfected
      root segments colonised with Glomus claroideum BEG23 was measured after 5 days
      incubation in liquid media. When only Mn ions were present in the media at higher
      concentrations (>0.05 mM), the growth of hyphae from root segments was reduced
      significantly. Addition of magnesium sulphate to the incubation solution reduced
      the inhibitory effects of Mn on hyphal growth. Alleviation of Mn toxicity by Mg
      ions observed in in vitro experiments was verified also for the symbiotic
      association between G. claroideum and maize as a host plant in a hydroponics sand
      culture experiment.

PMID- 12072983
TI  - Use of different nitrogen sources by the edible ectomycorrhizal mushroom
      Cantharellus cibarius.
AB  - The growth of three strains of Cantharellus cibarius on liquid media containing
      ammonium, nitrate and bovine serum albumin (BSA) in different combinations was
      determined. The most readily utilisable source of N was ammonium. BSA utilisation
      was limited compared with media containing ammonium. Growth on nitrate was also
      poor, suggesting a limited capacity of C. cibarius to metabolise this nitrogen
      source. There was some indication of considerable intraspecific variation within
      C. cibarius in the utilisation of nitrogen sources. Possible links between
      atmospheric nitrogen deposition and the observed decrease of sporocarp formation
      by C. cibarius in Europe are discussed. We highlight the potential ecological
      significance of bacteria associated with C. cibarius which may circumvent the
      need for fungal extracellular enzymes to access complex nitrogen sources.

PMID- 12072984
TI  - Interaction between Laccaria laccata and Trichoderma virens in co-culture and in
      the rhizosphere of Pinus sylvestris grown in vitro.
AB  - Interactions between the ectomycorrhizal fungus Laccaria laccata and the soil
      fungus Trichoderma virens in co-culture and in the rhizosphere of Pinus
      sylvestris seedlings growing in vitro were investigated by light and scanning
      electron microscopy. The growth of T. virens was inhibited in co-culture.
      Shortened, more branched and sometimes deformed or injured hyphae of T. virens
      were observed in the zone of inhibition. Two-month-old mycorrhizae of P.
      sylvestris/ L. laccata were inoculated with a conidial suspension of T. virens
      and examined at intervals of 7-24 h and 2, 3, and 6 days post-inoculation (p.i.).
      On non-mycorrhizal roots, conidia germination was high and long hyphae formed 3
      days p.i. On mycorrhizal roots, short germ tubes were observed only sporadically.
      At 3 days p.i., the mantle hyphae of L. laccata grew towards the conidia and
      coiled around them. Extremely dense coils of hyphae were found around clusters of
      conidia. Deformation of conidia, breaks in conidial walls and their partial
      degradation were observed 6 days p.i.

PMID- 12072985
TI  - Ectomycorrhizal root development in wet Alder carr forests in response to
      desiccation and eutrophication.
AB  - Effects of desiccation and eutrophication on ectomycorrhizal (ECM) root
      development in wet Alder carr forests in The Netherlands were studied. In
      northwestern Europe, wet Alder carr forests are found mostly in peatlands and
      along streams, forming an important component of wetland ecosystems. The dominant
      tree species in wet Alder carr forests is Alnus glutinosa (L.) Gaertn. (Black
      alder), which associates with ectomycorrhizal fungi. During recent decades, wet
      Alder carr forests in Europe have declined because of desiccation and
      eutrophication, particularly in The Netherlands. In the present study, the number
      of root tips of A. glutinosa trees was highest in an undisturbed wet Alder carr
      forest in a peatland area. Eutrophication in the peatland area significantly
      inhibited ectomycorrhizal (ECM) root development of A. glutinosa. In the
      eutrophied forest, ECM root tips were observed only close to A. glutinosa trees
      growing on hummocks. The concentrations of nitrate and potassium in soil water of
      the eutrophied forest were significantly higher than in the undisturbed forest,
      while magnesium and iron concentrations and the pH were significantly lower. The
      number of ECM root tips of A. glutinosa in a desiccated forest along a stream was
      generally lower than in an undisturbed wet Alder carr forest on waterlogged soil
      in the same area. The sulphate concentration in soil water in the desiccated
      forest was significantly higher than in the forest on waterlogged soil. ECM root
      development of A. glutinosa may have been negatively affected by the chemical
      composition of the soil water.

PMID- 12072986
TI  - Influence of restoration on arbuscular mycorrhiza of Biscutella laevigata L.
      (Brassicaceae) and Plantago lanceolata L. (Plantaginaceae) from calamine spoil
      mounds.
AB  - The arbuscular mycorrhizal status of two plant species, Biscutella laevigata L.
      and Plantago lanceolata L., was investigated on calamine spoil mounds in Boleslaw
      (southern Poland). Although B. laevigata is a member of the Brassicaceae, a
      family generally accepted as non-mycorrhizal, this species formed AM symbioses on
      both heavy metal-contaminated and non-contaminated sites. Besides vesicles and
      coils, arbuscules were also observed, especially in roots collected prior to seed
      maturity. Relative mycorrhizal root length and relative arbuscular richness were
      usually much higher in P. lanceolata than in B. laevigata but not absolute
      arbuscule richness. Roots of P. lanceolata showed higher colonisation than B.
      laevigata. Although roots were collected from plants in close proximity, no
      correlation in mycorrhizal parameters was found between the two species.

PMID- 12072989
TI  - A technique for thoracoscopic aortopericardiosternopexy.
AB  - BACKGROUND: A left thoracotomy is the standard access for aortosternopexy in
      severe tracheomalacia. We report a modified technique for thoracoscopic
      aortopericardiosternopexy. METHODS: The thymus is mobilized, and the needle is
      passed through the sternum and back. In extensive or recurrent tracheomalacia,
      not only the ascending aorta but also the innominate artery and pericardial base
      are fixed to the sternum. The effect is monitored bronchoscopically. RESULTS:
      This technique showed dramatic success in two children, one 4-year-old and a 2
      year-old. In the younger child, the thoracoscopy was a redo procedure after a
      previous open aortosternopexy. CONCLUSIONS: Thoracoscopic
      aortopericardiosternopexy is an effective procedure that does not impair
      postoperative respiration. It should therefore be considered for severe
      tracheomalacia or even redo operations.

PMID- 12072988
TI  - Management of peritoneal tear during endoscopic extraperitoneal inguinal
      hernioplasty.
AB  - BACKGROUND: Peritoneal tear during endoscopic extraperitoneal inguinal
      hernioplasty (TEP) results in pneumoperitoneum and loss of extraperitoneal space.
      To avoid bowel adhesions, internal herniation, and mesh migration, closure of the
      peritoneal opening is preferred. The present study was conducted to evaluate the
      efficacy of various operative techniques for the closure of peritoneal
      laceration. METHODS: Between April 2000 and May 2001, 100 consecutive patients
      undergoing 123 TEPs were recruited for the present study. The incidence of
      peritoneal tear and techniques for the closure of peritoneal opening were
      documented. Operative time and postoperative morbidity were compared among groups
      for which different closure methods of peritoneal laceration were used. RESULTS:
      The incidence of peritoneal tear was 47%. The mean operative times of unilateral
      TEPs with and without peritoneal laceration were 66 min and 53 min, respectively
      (p<0.05). Techniques for the closure of the peritoneal opening included
      endoscopic stapling (n = 12), endoscopic suturing (n = 14), and pretied suture
      loop ligation (n = 21). The mean operative times for unilateral TEPs with
      endoscopic stapling, pretied suture loop ligation, and endoscopic suturing of
      peritoneal tear were 53, 64, and 82 min, respectively (p<0.05). Comparison of
      postoperative morbidity showed no significant differences among the three groups.
      CONCLUSION: Peritoneal tear is a frequent and challenging intraoperative event
      during TEP. Its occurrence significantly prolongs the length of operation.
      Endoscopic stapling and pretied suture loop ligation are safe and quick
      techniques for the closure of peritoneal tear during TEP.

PMID- 12072991
TI  - A clearly visible endoscopic instrument shaft on the monitor facilitates hand-eye
      coordination.
AB  - BACKGROUND: Passing an instrument through a small incision alters the kinematics
      of the instrument, thus hampering hand-eye coordination. Nevertheless, the
      incision provides a stable, nearly invariant, point of rotation for instrument
      movements. Therefore, we set out to evaluate the effects of the altered
      kinematics on hand-eye coordination. In addition, we assessed the hypothesis that
      the hand-eye coordination of laparoscopic surgeons incorporates the incision as a
      point of reference. METHODS: Eight surgeons with experience in laparoscopy
      repeatedly performed a positioning task on a two-dimensional endoscopic
      manipulation simulator. Task time was measured. In the first experiment, normal
      endoscopic manipulation was compared to a condition in which the kinematic
      effects of the incision were compensated for. In the second experiment, the
      instrument shaft on the monitor was not visible during half of the trials, so
      that all visual information about the location of the incision was obscured.
      RESULTS: Task performance improved significantly when the kinematic effects of
      the incision were compensated for (p = 0.001). Task performance improved when the
      instrument shaft was clearly visible on the monitor (p <0.05). CONCLUSIONS:
      Compensating for the kinematic effects introduced by the incision improves hand
      eye coordination. The results of this study indicate that the incision provides a
      point of reference for hand-eye coordination during endoscopic manipulation.

PMID- 12072992
TI  - The laparoscopic approach with antireflux surgery is superior to the
      thoracoscopic approach for the treatment of esophageal achalasia. Experience of a
      single surgical unit.
AB  - BACKGROUND: Since its first description in the early 1990s, minimally invasive
      Heller myotomy has become the treatment of choice for esophageal achalasia. We
      report the experience of a single unit with thoracoscopic Heller myotomy (THM)
      and laparoscopic Heller myotomy (LHM) and we analyze the short- and long-term
      surgical outcomes in patients treated by each of the two approaches. METHODS: We
      evaluated retrospectively 33 patients who underwent surgical treatment for
      achalasia. Sixteen patients underwent THM without an antireflux procedure, and 17
      patients underwent LHM and partial anterior fundoplication (n = 10) or closure of
      the angle of His (n = 7). RESULTS: Mean operative time was significantly shorter
      for LHM than for THM (150 vs 222 min, respectively) (p = 0.0001). Mean hospital
      stay was significantly shorter after LHM than after THM (2.0 +/- 1.0 vs 5.1 +/-
      2.2 days, respectively) (p = 0.0001). Six of 16 patients (37.5%) in the THM group
      experienced persistent or recurrent dysphagia compared to one of 17 patients
      (5.8%) in the LHM group (p = 0.04). Heartburn developed in five patients (31.2%)
      after THM and in one patient (5.8%) after LHM (p = 0.07). Regurgitation developed
      in four patients (25%) after THM and in one patient (5.8%) after LHM (p = 0.149).
      Lower esophageal sphincter (LES) basal pressure decreased significantly from 30.1
      +/- 5.07 to 15.3 +/- 2.1 after THM and from 32.1 +/- 5.9 to 10.5 +/- 1.7 after
      LHM (p = 0.0001). Mean esophageal diameter was significantly reduced after LHM
      compared to THM (from 54.5 +/- 5.7 mm to 27.1 +/- 3.3 mm vs 50.8 +/- 7.6 mm to
      37.2 +/- 6.9 mm, respectively) (p = 0.0001). CONCLUSION: In our experience, LHM
      is associated with a shorter operative time and a shorter hospital stay, and it
      is superior to THM in relieving dysphagia. LHM with partial anterior
      fundoplication should be considered the treatment of choice for achalasia.

PMID- 12072993
TI  - Laparoscopic pancreas-preserving distal duodenectomy for duodenal stricture
      related to nonsteroidal antiinflammatory drugs (NSAIDs).
AB  - BACKGROUND: Chronic ingestion of nonsteroidal antiinflammatory drugs (NSAIDs) has
      rarely been associated with the development of intestinal diaphragm-like
      strictures. We have explored the role of laparoscopic surgery for the management
      of NSAID-related long distal duodenal strictures. METHOD: A 49-year-old woman had
      been on NSAID therapy (ibuprofen) for backache more than 2 years. She showed
      symptoms of gastric outlet obstruction and gastrointestinal blood loss, and
      investigations showed a long stricture in the third and fourth parts of the
      duodenum. She underwent a laparoscopic pancreas-preserving distal duodenectomy
      with duodenojejunal anastomosis. RESULT: Relaparoscopy on postoperative day 1 for
      bleeding showed no active source of bleeding. The patient's subsequent recovery
      was uneventful, and she was discharged on postoperative day 4. Further
      symptomatic strictures developed 2 months later at the previously ulcerated
      pylorus and distal duodenal bulb and were managed by a laparoscopic Roux-en-Y
      gastrojejunostomy. The patient was discharged on postoperative day 3, but
      represented 2 months later with symptomatic stenosis at the gastrojejunostomy
      which was managed by a laparoscopic revision gastrojejunostomy. Discharged on the
      postoperative day 2, she had regained weight and remained symptom free at follow
      up assessment 3 months later. CONCLUSION: Laparoscopic pancreas-preserving distal
      duodenectomy for the management of benign duodenal strictures is feasible and
      safe. Moreover, we have demonstrated the beneficial role of relaparoscopy for the
      management of postoperative complications and for revision surgical procedures.

PMID- 12072994
TI  - Laparoscopic transgastric pancreatic necrosectomy for infected pancreatic
      necrosis.
AB  - BACKGROUND: Secondary infection of pancreatic necrosis is an indication for
      surgical debridement, and has traditionally been treated by laparotomy, and more
      recently by laparoscopic transmesocolic or transgastrocolic and
      retroperitoneoscopic approaches. This report describes and evaluates the safety
      and feasibility of a laparoscopic transgastric approach to extensive necrosectomy
      for infected pancreatic necrosis. METHOD: A 66-year-old man developed severe
      acute pancreatitis with more than 50% necrosis of the body and some necrosis of
      the tail of the gland. Clinical deterioration with respiratory and renal
      impairment at 2 weeks prompted a computed tomogram (CT) guided fine-needle
      aspiration of the necrosis, which proved to be infected with Gram-negative
      bacilli. A favorable response to supportive therapy and systemic antibiotics
      enabled a cautious deferment of surgery to week 6 of the illness while the
      necrosis and its inflammatory wall matured. A laparoscopic transgastric
      pancreatic necrosectomy with drainage of an associated abscess was performed.
      RESULT: Intraoperative blood loss was minimal, and Operative time was 270 min.
      The debrided pancreas (30 g) was infected with anaerobes. The patient made an
      uneventful recovery and was discharged on postoperative day 14. At this writing,
      he remains well after 2 months of follow-up evaluation. CONCLUSION: Laparoscopic
      transgastric pancreatic necrosectomy appears to be a safe and effective minimally
      invasive approach for the debridement and internal drainage of infected
      pancreatic necrosis in the selected patient. Further experience with this
      technique is needed to define the selection criteria and its limitations,
      advantages, and disadvantages.

PMID- 12072995
TI  - Congenital double pyloric ostium in the adult.
AB  - Duplication of the pylorus, an extremely rare congenital anomaly of the stomach,
      consists of two openings connecting the antrum of the stomach to the duodenal
      bulb. Approximately 70 cases of double pylorus have been described in the
      literature, most of which are associated with the presence of chronic peptic
      ulcers, thus indicating an acquired origin of the condition. We report a case of
      congenital double pylorus in a 64-year-old man who complained about mild
      postprandial epigastric discomfort and nausea of approximately 3 months'
      duration. Endoscopic examination of the stomach showed a double pyloric ostium
      connecting the stomach to the duodenum. No signs of acute or chronic peptic ulcer
      were noted. A biopsy was taken from the region between the two openings, which
      showed normal mucosa and a muscularis mucosae layer. Apart from a mild gastritis,
      no other pathology (chronic peptic ulcer, ulcerated malignancy) suggesting an
      acquired origin of the double pylorus was observed. Therefore, the case was
      considered to be congenital in origin. The patient was successfully treated
      conservatively with antacids and gastrokinetics.

PMID- 12072996
TI  - Laparoscopic hepatectomy for extrahepatic growing tumor. Surgical strategy based
      on extrahepatic growing index.
AB  - BACKGROUND: This article describes the operative procedures, varying
      difficulties, and required instrumentation for performing laparoscopic
      hepatectomy (LH) on the basis of a lesion's extrahepatic growing (EG) index, as
      calculated by computed tomography (CT). METHODS: Laparoscopic partial hepatectomy
      cases were divided into the following two groups: an EG tumor group (n = 11) and
      an intrahepatic tumor group (n = 8). The surgical procedures, operative results,
      and laparoscopic instrumentation for these two groups were compared based on the
      EG index (/cm2; maximum diameter of tumor pedicle/maximum vertical diameter of
      tumor/area of the tumor). RESULTS: The mean operative time was significantly
      shorter and the mean blood loss was significantly less in the EG tumor group than
      in the intrahepatic tumor group. In addition, in the EG tumor group, there were
      significant differences in mean operative time and mean blood loss related to the
      values associated with the EG index (p <0.05, P <0.01). The selection of
      laparoscopic instruments was based on the EG index, as follows: (a) lesions with
      an EG index >5/cm2 underwent resection in combination with a microwave tissue
      coagulator and an ultrasonic surgical aspirator (13 cases, including intrahepatic
      tumor cases); (b) lesions with an EG index of 5-15/cm2 underwent resection in
      combination with a microwave tissue coagulator and laparosonic coagulating shears
      (four cases); (c) lesions with an EG index <%15/cm2 underwent resection with a
      laparoscopic linear stapler (two cases). CONCLUSION: Our preliminary experience
      leads us to believe that it is useful to calculate the EG index by CT scan before
      formulating the technical strategy for a subsequent LH procedure.

PMID- 12072997
TI  - Serum E-cadherin concentrations and their response during laparoscopic and open
      cholecystectomy.
AB  - BACKGROUND: Elevated serum levels of the cell adhesion molecule E-cadherin have
      been associated with the presence of tissue injury and inflammation. We compared
      soluble E-cadherin response during laparoscopic and open cholecystectomy.
      METHODS: The E-cadherin response to surgery was studied in 16 patients undergoing
      laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy.
      Serum E-cadherin levels were measured by an enzyme immunoassay (ELISA)
      preoperatively, 10 and 30 min after the commencement of surgery, and at 6 and 24
      h following the operation. RESULTS: Serum E-cadherin levels decreased
      progressively during laparoscopic cholecystectomy; their concentrations at 24 h
      after surgery were significantly lower when compared with preoperative values. In
      the open cholecystectomy group, serum E-cadherin levels did not differ from
      preoperative values at any time point. Serum E-cadherin concentrations at 24 h
      after surgery and the cumulative E-cadherin response were significantly higher in
      the open cholecystectomy group than in the laparoscopic group. CONCLUSION:
      Compared with open cholecystectomy, the cumulative E-cadherin response is
      significantly reduced following laparoscopic cholecystectomy.

PMID- 12072998
TI  - Quality of life for patients with gastroesophageal reflux disease 2 years after
      laparoscopic fundoplication. Evaluation of the results obtained during the
      initial experience.
AB  - BACKGROUND: Health-related quality of life (HRQL) is significantly affected by
      gastroesophageal reflux disease (GERD), and its evaluation is emerging as a
      factor important to select treatment options for GERD. Antireflux laparoscopic
      surgery improves HRQL. The aim of this study was to compare the preoperative and
      medium-term postoperative HRQL in patients submitted to laparoscopic
      fundoplication during the initial experience to verify its possible influence on
      HRQL outcomes. METHODS: Clinical assessment, endoscopy, and a previously
      validated HRQL index were performed before and 2 years after surgery in 32
      patients who underwent at the beginning of our experience. RESULTS: The
      esophageal mucosa returned to normal 2 years after laparoscopic fundoplication in
      81% of the patients. Heartburn was absent or occasional in 93%, and 65% were free
      of antisecretory drugs. All postoperative HRQL items were significantly improved
      (p <0.0001), with the postoperative curve of HRQL scores superposable to those of
      healthy Italian subjects (Italian normative sample). CONCLUSIONS: The initial
      phase of learning does not affect the improvement of HRQL observed after
      laparoscopic antireflux surgery, which is consistent with durable relief of
      symptoms and endoscopic healing. Evaluation of HRQL should be added to, and
      probably could replace in most cases, the objective postoperative testing.

PMID- 12072999
TI  - Laparoscopic-endoscopic rendezvous resection of gastric tumors.
AB  - BACKGROUND: Submucosal and mucosal tumors of the stomach display a wide spectrum
      of histopathologic and prognostic characteristics. Biopsies obtained using
      endoscopic techniques often do not provide the representative histologic sample
      needed for further therapeutic decisions. METHODS: From 1999 to 2002, 18 patients
      with gastric tumors underwent a combined endoscopic-laparoscopic local resection
      of the tumors using two different procedures and were prospectively analyzed.
      Tumors of the posterior wall were resected using laparoscopic intragastral
      resection (LIR). Tumors located in the anterior wall were resected using lesion
      lifting or the laparoscopic wedge resection (LWR) approach. RESULTS: Laparoscopic
      resections were performed in 18 patients. The mean age of the patients was 64.4
      years (range, 38-81 years). Preoperative preparation included endoscopy with
      biopsies and histologic examination, ultrasound examination, computed tomography
      scan, and endoscopic ultrasonography. We performed the LWR on 10 patients and the
      LIR on 8 patients. After resection, the final immunohistologic examination of the
      specimens showed gastrointestinal stroma cell tumors in nine cases, neurinomas or
      benign neurofibrotic tumors in four cases, and one leiomyoma. Four additional
      patients with mucosal early gastric cancer and high comorbidity risks also
      underwent a limited full-thickness wedge resection. In all the patients, the
      surgical margins were tumor free, and no lymphatic or venous invasion was
      encountered in pathologic specimens. Method-specific complications occurred in
      one case (perforation of the stomach wall). No fatal outcome had to be
      registered. CONCLUSIONS: When selected properly, the laparoscopic-endoscopic
      approach is considered to be curative and minimally invasive for resection of
      localized gastric tumors. In cases of histopathologically unknown tumors
      preoperatively, definitive examination of the complete specimen provides the
      basis for further therapeutic decisions.

PMID- 12073001
TI  - Early laparoscopic appendectomy for appendicular mass.
AB  - BACKGROUND: The surgical management of acute appendicitis presenting with
      appendicular mass remains controversial. The aim of this study was to evaluate
      the role of early laparoscopy and laparoscopic appendectomy (LA) in the
      management of appendicular mass. METHODS: During a 1-year period, 62 patients
      underwent LA for suspected appendicitis (n = 50), generalized peritonitis (n =
      2), and an appendicular mass (n = 10). Another patient who presented with an
      appendicular mass was found at laparoscopy to have an ileo-ileal intussusception.
      RESULTS: All appendectomies were attempted and completed laparoscopically.
      Postoperative complications occurred in two patients; there were no deaths. None
      of the patients treated for an appendicular mass developed complications. There
      was no difference between the patients who underwent LA during the index
      admission for an appendicular mass and those who had surgery for non-mass-forming
      appendices with regard to the operative time (median [interquartile range]: 45
      [36-60] vs 40 [25-50] min, p = 0.085) and postoperative hospital stay (median
      [interquartile range]: 2 [1-2] vs [1-2] days, p = 0.1). CONCLUSION: Early LA
      during the index admission of patients with an appendicular mass is feasible and
      safe, obviates the need for a second hospital admission, and avoids misdiagnoses.

PMID- 12073000
TI  - Abnormal esophageal acid exposure is common in morbidly obese patients and
      improves after a successful Lap-band system implantation.
AB  - BACKGROUND: The relation between gastro-esophageal reflux disease (GERD) and
      obesity is controversial. The laparoscopic adjustable gastric band (LAGB)
      procedure is effective for morbid obesity. Its indication in the presence of
      GERD, however, is still debated. This study aimed to investigate esophageal
      symptoms, motility patterns, and acid exposure in morbidly obese patients before
      and after LAGB placement. METHOD: For this study, 43 consecutive obese patients
      were investigated by a standardized symptoms questionnaire, stationary manometry
      and 24-h ambulatory pH-metry, and 16 patients with abnormal esophageal acid
      exposure were reevaluated 18 months after LAGB placement. RESULTS: Symptom scores
      and abnormal esophageal acid exposure were found to be significantly higher,
      Lower Esophageal Sphincter (LOS) pressure was significantly lower in obese
      patients than in control subjects. After LAGB, esophageal acid exposure was
      significantly reduced in all but two patients, who presented with proximal of
      gastric pouch dilation. CONCLUSIONS: There is a high prevalence of GERD in the
      obese population. Uncomplicated LAGB placement reduces the amount of acid in
      these patients with abnormal esophageal acid exposure.

PMID- 12073003
TI  - Gastrointestinal transit and stress response after laparoscopic vs conventional
      distal pancreatectomy in the canine model.
AB  - BACKGROUND: Several authors have presented the feasibility of laparoscopic
      pancreatic surgery. However, the pathophysiological effect of laparoscopic
      pancreatic surgery is not well known. METHODS: Ten mongrel dogs were randomly
      operated for laparoscopic and conventional distal pancreatectomy. Fed state
      gastrointestinal transit times were assessed using radiopaque markers. To assess
      surgical stress, we determined serum IL-1 and cortisol. RESULTS: Postoperative
      mouth-to-anus transit time in the laparoscopic group was not prolonged while it
      was significantly prolonged in the conventional group compared with the baseline
      study, but no significant differences between groups were detected. First
      defecation was observed significantly earlier in the laparoscopic group. Serum
      cortisol levels were elevated significantly at 4 h after skin incision in both
      groups and decreased thereafter. In the laparoscopic group, they returned close
      to the normal level at 8 h after incision, but were still significantly higher in
      the conventional group. The level of IL-1 was elevated significantly higher in
      conventional group at 24 h after the skin incision. CONCLUSION: Thus, we conclude
      that laparoscopic distal pancreatectomy demonstrated faster recovery of the bowel
      transit and less stress than conventional distal pancreatectomy in dogs.

PMID- 12073002
TI  - Usefulness of self-expandable metallic stent with an antireflux mechanism as a
      palliation for malignant strictures at the gastroesophageal junction.
AB  - BACKGROUND: Patients with unresectable malignant gastroesophageal strictures
      often are troubled with reflux esophagitis after stent placement. METHODS: A self
      expandable metallic stent (SEMS) without an antireflux mechanism was placed in
      seven patients with unresectable malignant gastroesophageal strictures (group A),
      and SEMS with an antireflux mechanism was placed in five patients (group B).
      After we obtained monitoring systems, two patients in group A and all the
      patients in group B underwent measurement of bilirubin and pH in the esophagus
      using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total time
      less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and
      64.0% in group A. The mean percentage of total time for a pH less than 4 was 2.9%
      in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the
      antireflux mechanism can be effective not only for palliation of gastroesophageal
      stricture, but also for prevention of reflux.

PMID- 12073005
TI  - Laparoscopic gatrojejunostomy for palliation of gastric outlet obstruction in
      unresectable gastric cancer.
AB  - BACKGROUND: Gastric bypass through laparotomy is required traditionally when
      gastric outlet obstruction occurs secondary to a disease process (e.g.,
      unresectable cancer). The recent trend toward minimally invasive procedures has
      led us to apply laparoscopic bypass surgery for gastric obstruction caused by
      unresectable advanced gastric cancer. METHODS: From March 1998 to February 2000,
      78 gastrojejunostomies (GJ) (45 open [OGJ] and 33 laparoscopic [LGJ] procedures)
      were performed for palliation of gastric outlet obstruction caused by advanced
      gastric, duodenal, papilla of vater, and pancreatic cancers at the Asan Medical
      Center. In 68 patients with advanced gastric cancer, OGJ (n = 38) and LGJ (n =
      30) were performed. Of these, 10 OGJ patients were compared with 10 diagnosis
      matched LGJ control subjects who underwent surgery during the same period in
      terms of age, gender, American Society of Anesthesiology (ASA) grading, previous
      abdominal surgery, operating time, time to oral food intake, pain-killer
      consumption, postoperative hospital stay, immune response, morbidity, and
      mortality. Immune parameters including serum white blood cells (WBC) count, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), cortisol, and
      erythrocyte sedimentation rate (ESR) levels were assessed preoperatively and on
      postoperative days 1 and 3 between the two groups. With the patients under the
      general endotracheal anesthesia, we applied an upper midline incision in OGJ and
      inserted four trocars in LGJ. Side-to-side gastrojejunostomy was performed in a
      standard fashion. In LGJ, intracorporeal suture using 2-0 vicryl was performed to
      repair the gastrotomy and jejunotomy site after gastrojejunostomy using a 30-mm
      or 45-mm Endo-GIA stapler. RESULTS: There were no significant differences between
      OGJ and LGJ in terms of gender, age, ASA grading, and previous abdominal surgery.
      In OGJ, antecolic isoperistaltic GJ was performed in 10 cases, but 8 antecolic
      and 2 retrocolic approaches were performed in LGJ with no conversion to open
      surgery. Operating time (113.5 +/- 11.2 vs 100.5 +/- 9.8 min), pain-killer
      consumption (540 +/- 123.2 vs 430 +/- 58.2 mg), and postoperative hospital stay
      (12.5 +/- 3.9 vs 8.5 +/- 2.9 days) were reported, respectively. Serum WBC and
      cortisol levels were slightly increased in both groups preoperatively and on
      postoperative days 1 and 3. Serum ESR, TNF-alpha, and IL-6 levels were
      significantly increased in the OGJ patients. Postoperative complications (9 with
      OGJ and 2 with LGJ) and postoperative death (1 in each group) occurred. During
      the follow-up period (3-23 months), there was one case of readmission in each
      group because of anemia and generalized pain. CONCLUSIONS: Laparoscopic GJ for
      the palliation of unresectable advanced gastric cancer can achieve excellent
      results with less suppression of immune function, lower morbidity, greater
      improvement of hemodynamic activities, and earlier recovery of bowel movements
      than OGJ.

PMID- 12073004
TI  - Complications and feasibility of laparoscopic adhesiolysis in patients with
      chronic abdominal pain. A retrospective study.
AB  - BACKGROUND: A retrospective study was done to determine whether laparoscopic
      adhesiolysis benefits patients with chronic abdominal pain. Factors that
      influence complications and feasibility of laparoscopic adhesiolysis were
      evaluated. METHODS: 174 consecutive operations in 157 patients were
      retrospectively analyzed for factors which might influence the complication rate
      and the feasibility of laparoscopic adhesiolysis. RESULTS: In 128 out of 174
      procedures a complete adhesiolysis was performed. We had to accept an incomplete
      adhesiolysis in 39 other patients and in 7 patients a primary conversion was
      needed. We noticed 16 major complications. Two patients died. Relief of pain was
      recorded in 80% of patients after short follow-up. The number of previous
      abdominal operations and patient age significantly affected the outcome of
      surgery. CONCLUSION: Laparoscopic adhesiolysis in patients with chronic abdominal
      pain seems to be a feasible and effective operation with considerable risk.

PMID- 12073006
TI  - Successful treatment of duodenal bulb obstruction caused by a gallstone
      (Bouveret's syndrome) after endoscopic mechanical lithotripsy.
AB  - Because of acute symptoms in the upper abdomen, upper gastrointestinal endoscopy
      was performed in a 68-year-old man. A large perforated gallstone was embedded in
      the duodenum, causing complete obstruction of the duodenal bulb. The stone was
      crushed successfully by endoscopic mechanical lithotripsy. The patient was
      referred for surgery, and was discharged after a successful and uneventful
      cholecystectomy.

PMID- 12073007
TI  - Mutations in the WFS1 gene that cause low-frequency sensorineural hearing loss
      are small non-inactivating mutations.
AB  - Hereditary hearing impairment is an extremely heterogeneous trait, with more than
      70 identified loci. Only two of these loci are associated with an auditory
      phenotype that predominantly affects the low frequencies (DFNA1 and DFNA6/14). In
      this study, we have completed mutation screening of the WFS1 gene in eight
      autosomal dominant families and twelve sporadic cases in which affected persons
      have low-frequency sensorineural hearing impairment (LFSNHI). Mutations in this
      gene are known to be responsible for Wolfram syndrome or DIDMOAD (diabetes
      insipidus, diabetes mellitus, optic atrophy, and deafness), which is an autosomal
      recessive trait. We have identified seven missense mutations and a single amino
      acid deletion affecting conserved amino acids in six families and one sporadic
      case, indicating that mutations in WFS1 are a major cause of inherited but not
      sporadic low-frequency hearing impairment. Among the ten WFS1 mutations reported
      in LFSNHI, none is expected to lead to premature protein truncation, and nine
      cluster in the C-terminal protein domain. In contrast, 64% of the Wolfram
      syndrome mutations are inactivating. Our results indicate that only non
      inactivating mutations in WFS1 are responsible for non-syndromic low-frequency
      hearing impairment.

PMID- 12073008
TI  - Estimation of single nucleotide polymorphism allele frequency in DNA pools by
      using Pyrosequencing.
AB  - Positional cloning of genes underlying complex diseases, such as type 2 diabetes
      mellitus (T2DM), typically follows a two-tiered process in which a chromosomal
      region is first identified by genome-wide linkage scanning, followed by
      association analyses using densely spaced single nucleotide polymorphic markers
      to identify the causal variant(s). The success of genome-wide single nucleotide
      polymorphism (SNP) detection has resulted in a vast number of potential markers
      available for use in the construction of such dense SNP maps. However, the cost
      of genotyping large numbers of SNPs in appropriately sized samples is nearly
      prohibitive. We have explored pooled DNA genotyping as a means of identifying
      differences in allele frequency between pools of individuals with T2DM and
      unaffected controls by using Pyrosequencing technology. We found that allele
      frequencies in pooled DNA were strongly correlated with those in individuals
      (r=0.99, P<0.0001) across a wide range of allele frequencies (0.02-0.50). We
      further investigated the sensitivity of this method to detect allele frequency
      differences between contrived pools, also over a wide range of allele
      frequencies. We found that Pyrosequencing was able to detect an allele frequency
      difference of less than 2% between pools, indicating that this method may be
      sensitive enough for use in association studies involving complex diseases where
      a small difference in allele frequency between cases and controls is expected.

PMID- 12073009
TI  - Nuclear mitochondrial interplay in the modulation of the homopolymeric tract
      length heteroplasmy in the control (D-loop) region of the mitochondrial DNA.
AB  - We have studied the genetic characteristics of a homopolymeric tract length
      heteroplasmy associated with the 16189C variant in the mtDNA D-loop control
      region to identify the factor(s) involved in the generation of the length
      heteroplasmy. The relative proportion of the various lengths of the polycytosines
      (i.e., the pattern of the length heteroplasmy) is maintained in an individual,
      and previous evidence shows that it is regenerated de novo following cell
      divisions. The pattern is maintained in maternally related individuals,
      suggestive of mtDNA determinants. Of the 38 individuals with the 16189C variant
      studied, 39% were found to exhibit the (16180)AAACCCCCCCCCCC(16193) variant
      associated with A16183C polymorphism [(11C)-group], while 53% showed the
      (16180)AACCCCCCCCCCCC(16193) variant associated with a further A16182C
      polymorphism [(12C)-group]. Haplotype analysis of the mtDNA revealed a specific
      association of the longer mean length of the poly[C] in the (12C)-group with
      haplogroup B. A similar association was also observed in the (11C)-group, but
      with a novel haplogroup. Cybrid constructions revealed that the involvement of
      nuclear factor(s) in the generation of the length heteroplasmy is prominent in
      homopolymeric tract of eight cytosines. The nuclearly coded factor(s) is/are
      presumably related to the fidelity of the nuclearly coded components of the
      mitochondrial DNA replication machinery.

PMID- 12073011
TI  - Analysis of 22 deletion breakpoints in dystrophin intron 49.
AB  - Over 60% of Duchenne and Becker muscular dystrophies are caused by deletions
      spanning tens or hundreds of kilobases in the dystrophin gene. The molecular
      mechanisms underlying the loss of DNA at this genomic locus are not yet
      understood. By studying the distribution of deletion breakpoints at the genomic
      level, we have previously shown that intron 49 exhibits a higher relative density
      of breakpoints than most dystrophin introns. To determine whether the mechanisms
      leading to deletions in this intron preferentially involve specific sequence
      elements, we sublocalized 22 deletion endpoints along its length by a polymerase
      chain-reaction-based approach and, in particular, analyzed the nucleotide
      sequences of five deletion junctions. Deletion breakpoints were homogeneously
      distributed throughout the intron length, and no extensive homology was observed
      between the sequences adjacent to each breakpoint. However, a short sequence able
      to curve the DNA molecule was found at or near three breakpoint junctions.

PMID- 12073010
TI  - Genetic diversity and evolution of the human leptin locus tetranucleotide repeat.
AB  - To better understand the evolutionary history of the gene region containing the
      multifunctional adipose tissue hormone leptin, we genotyped 1,957 individuals
      from 12 world populations for a highly variable tetranucleotide repeat
      polymorphism located 476 bp 3' of exon 3 of the leptin gene. Common alleles
      shared among populations, alleles specific to geographically defined populations,
      and the homologous alleles in the common and pygmy chimpanzee, the gorilla and
      the orangutan, were sequenced to define the allelic variation at the nucleotide
      level. These data reveal a common set of alleles shared among world populations,
      presumed to have arisen from a great ape ancestral allele prior to the divergence
      of the major geographical subdivisions of the human population, a subset of
      alleles specific to populations of African ancestry and a second set of alleles
      that arose by tandem duplication of the core repeat unit following the separation
      of African and non-African populations. These findings emphasize the complex
      evolutionary history of this locus and raise cautions about the pooling of
      alleles at this locus in association studies.

PMID- 12073012
TI  - A loss-of-function mutation in the CFC domain of TDGF1 is associated with human
      forebrain defects.
AB  - TDGF1 (CRIPTO) is an EGF-CFC family member and an obligate co-receptor involved
      in NODAL signaling, a developmental program implicated in midline, forebrain, and
      left-right axis development in model organisms. Previous studies of CFC1
      (CRYPTIC), another member of the EGF-CFC family, demonstrated that normal
      function of this protein is required for proper laterality development in humans.
      Here we identify a mutation in the conserved CFC domain of TDGF1 in a patient
      with midline anomalies of the forebrain. The mutant protein is inactive in a
      zebrafish rescue assay, indicating a role for TDGF1 in human midline and
      forebrain development.

PMID- 12073013
TI  - Identification of additional transcripts in the Williams-Beuren syndrome critical
      region.
AB  - Williams-Beuren syndrome (WBS) is a developmental disorder associated with
      haploinsufficiency of multiple genes at 7q11.23. Here, we report the
      characterization of WBSCR16, WBSCR17, WBSCR18, WBSCR20A, WBSCR20B, WBSCR20C,
      WBSCR21, WBSCR22, and WBSCR23, nine novel genes contained in the WBS commonly
      deleted region or its flanking sequences. They encode an RCC1-like G-exchanging
      factor, an N-acetylgalactosaminyltransferase, a DNAJ-like chaperone,
      NOL1/NOP2/sun domain-containing proteins, a methyltransferase, or proteins with
      no known homologies. Haploinsufficiency of these newly identified WBSCR genes may
      contribute to certain of the WBS phenotypical features.

PMID- 12073014
TI  - FISH-mapping of a 100-kb terminal 22q13 deletion.
AB  - Both cytogenetically visible and cryptic deletions of the terminal region of
      chromosome 22q are associated with a clinical phenotype including mental
      retardation, delay in expressive speech development, hypotonia, normal to
      accelerated growth and minor facial dysmorphic features. The genes responsible
      for the development of the phenotype have not yet been identified, but a distal
      localization is probable, since the cytogenetically visible and the cryptic
      deletions show a similar pattern of symptoms. We report a 33-year-old woman with
      a submicroscopic 22q13 deletion, mild mental retardation, speech delay, autistic
      symptoms and mild facial dysmorphic features. The deletion was mapped by FISH
      using cosmid probes from terminal 22q13, and the size of the deletion was
      estimated to be 100 kb. Three genes are affected by the deletion in this patient.
      ACR and RABL2B are deleted and proSAP2 is disrupted. This observation, together
      with recently published data, supports the notion that proSAP2 is the most
      important contributor to the 22q13 deletion phenotype.

PMID- 12073016
TI  - Transmission disequilibrium test with discordant sib pairs when parents are
      available.
AB  - The transmission disequilibrium test (TDT) has been employed to map disease
      susceptibility loci (DSL), while being immune to the problem of population
      admixture. The customary TDT test (TDT(D)) was developed for affected child(ren)
      and their parents and was most often applied to case-parent trios. Recently, the
      TDT has been extended to the situations when (1) parents are not available but
      affected and nonaffected sibs from each family are available, (2) unrelated
      control-parent trios are available for combined analyses with case-parent trios
      (TDT(DC)), and (3) large pedigrees. For many diseases, affected children in the
      case-parent trios enlisted into the TDT(D) have unaffected sibs who can be
      recruited. We present an extension of the TDT by effectively incorporating one
      unaffected sib of each of the affected children in the case-parent trios into a
      single analysis (TDT(DS), where DS denotes discordant sib pairs). We have
      developed a general analytical method for computing the statistical power of the
      TDT(DS) under any genetic model, the accuracy of which is validated by computer
      simulations. We compare the power of the TDT(D), TDT(DC), and TDT(DS) under a
      range of parameter space and genetic models. We find that the TDT(DS) is
      generally more powerful than the TDT(DC) and TDT(D), particularly when the
      disease is prevalent (>30%) in the population. The relative power of the TDT(D)
      and the TDT(DS) largely depends upon the allele frequencies and genetic effects
      at the DSL, whereas the recombination rate, the degree of linkage disequilibrium,
      and the marker allele frequencies have little effect. Importantly, the TDT(DS)
      not only may be more powerful, it also has the advantage of being able to test
      for segregation distortion that may yield false linkage/association in the
      TDT(D).

PMID- 12073015
TI  - A novel and unusual case of chronic granulomatous disease in a child with a
      homozygous 36-bp deletion in the CYBA gene (A22(0)) leading to the activation of
      a cryptic splice site in intron 4.
AB  - Chronic granulomatous disease (CGD) is a rare congenital disorder in which
      phagocytes cannot generate superoxide (O(2)(-)) and other microbicidal oxidants
      because of mutations in one of the four components of the O(2)(-)-generating
      NADPH oxidase complex. A subgroup (approximately 5% of identified CGD patients)
      has been reported to have mutations in the gene encoding the small p22 phox
      subunit of the flavocytochrome b (558), the redox element of phagocyte NADPH
      oxidase. Here, we report the case of an autosomal recessive CGD patient with a
      defect in the p22 phox subunit. Neutrophils failed to produce O(2)(-) in response
      to soluble and particulate stimuli, and cytochrome b (558) was absent as measured
      by immunoblotting and difference absorption spectra. Mutations in the p22 phox
      mRNA of the patient were detected by reverse transcription/polymerase chain
      reaction amplification and sequencing. The defect in the mRNA was a 179-bp
      insertion associated with a 21-bp deletion of the beginning of exon 5 at position
      315 from the translation start codon of the p22 phox cDNA. This defect was also
      detected in the patient's parents. In the genomic DNA of the patient, the
      molecular defect was a homozygous 36-bp deletion in the linking sequence between
      intron 4 and exon 5. This genomic deletion corresponded to 15 bp of the 3'
      extremity of intron 4 and 21 bp of the beginning of exon 5 (the same deletion of
      exon 5 seen in the corresponding mRNA). The splicing mRNA error is attributable
      to the loss of the ag acceptor site of intron 4 and the utilization of a cryptic
      splice site with an ag sequence at position 355-356 of intron 4.

PMID- 12073017
TI  - Identity-by-descent approach to gene localisation in eight individuals affected
      by keratoconus from north-west Tasmania, Australia.
AB  - The minimum physical distance surrounding a candidate gene has been determined in
      founder populations by studying allele sharing and then mapping historical
      recombination events. In this study, we developed a novel minimalistic approach
      by using the genetically isolated population of Tasmania, Australia, to identify
      candidate gene loci in a small number of individuals of unknown genetic
      relationship affected by a dominant disorder. Keratoconus, an inheritable non
      inflammatory progressive degeneration of the cornea, is present at a five-fold
      increased incidence in Burnie, a coastal town on the island of Tasmania. Based on
      the fundamental assumption that individuals with keratoconus from this town are
      likely to be related through a founder effect, a 10-cM interval genome scan was
      conducted on six patients of undefined genetic relationship and one affected sib
      pair to identify commonly shared chromosomal segments for the elucidation of
      candidate gene loci. Analysis of allele sharing revealed four markers on three
      chromosomes where all eight individuals shared a common allele on at least one
      chromosome, and thirteen markers where all but one patient shared common alleles.
      No excess of allele sharing was observed at any marker tested on chromosome 21, a
      suggested candidate chromosome for keratoconus. Further analysis of positive loci
      revealed suggestive association at 20q12, where significant deviation in allele
      frequency D20S119 ( P=2.1 x 10(-5)) is observed when additional Tasmanian
      keratoconus samples are genotyped. Identification of a conserved minimal
      chromosomal haplotype around D20S119 in related Tasmanian patients suggests
      association with this locus, however association with the nearby candidate gene
      MMP-9 has been excluded.

PMID- 12073018
TI  - Universal, robust, highly quantitative SNP allele frequency measurement in DNA
      pools.
AB  - Detecting alleles that confer small increments in susceptibility to disease will
      require large-scale allelic association studies of single-nucleotide
      polymorphisms (SNPs) in candidate, or positional candidate, genes. However,
      current genotyping technologies are one to two orders of magnitude too expensive
      to permit the analysis of thousands of SNPs in large samples. We have developed
      and thoroughly validated a highly accurate protocol for SNP allele frequency
      estimation in DNA pools based upon the SNaPshot (Applied Biosystems) chemistry
      adaptation of primer extension. Using this assay, we were able to estimate the
      difference in allele frequencies between pooled cases and controls (Delta) with a
      mean error of 0.01. Moreover, when we genotyped seven different SNPs in a single
      multiplex reaction, the results were similar, with a mean error for Delta of
      0.008. The assay performed well for alleles of low frequency alleles (f
      approximately 0.05) and was accurate even with relatively poor quality DNA
      template extracted from mouthwashes. Our assay conditions are generalisable,
      universal, robust and, therefore, for the first time, permit high-throughput
      association analysis at a realistic cost.

PMID- 12073019
TI  - D-loop mutations in mitochondrial DNA: link with mitochondrial DNA depletion?
AB  - Clinical presentation of the patients with mitochondrial DNA depletion is quite
      diverse and is suggestive of genetic heterogeneity. Autosomal recessive
      inheritance of the disease appears likely, thus implying the nuclear origin of
      the disease. This has been demonstrated recently in large families with neonatal
      presentation of the disease. Here, we report upon a family with one child having
      a late-onset disease associated with severe mitochondrial DNA depletion. The
      presence of mitochondrial alterations in the muscle of the patient's mother
      prompted us to extensively analyse the mitochondrial DNA in the family. We found
      mitochondrial DNA multiple deletions, but also three heteroplasmic point
      mutations of the D-loop region, two of which (T119C and T408A) affect conserved
      regions involved in the mtDNA replication process. These mutations were non
      randomly distributed in the maternal lineage and, for one of them, among single
      muscle fibres. Involvement of the mitochondrial DNA in its own depletion appears
      therefore possible. It may act in close relationship with a hypothetical modified
      nuclear factor.

PMID- 12073021
TI  - RT-PCR splicing analysis of the NF1 open reading frame.
AB  - Neurofibromatosis 1 (NF1) is an autosomal dominant condition whose molecular
      diagnosis is challenging because of the large size of the gene and the vast
      number of unique NF1 gene mutations. Some splicing and nonsense mutations have
      been shown to cause exon skipping. Recently, temperature-induced abnormal
      splicing has been found in NF1 in ex-vivo tissues. This prompted us to
      investigate the entire NF1 transcript for such aberrant splicing. We found
      several novel exon skips that appeared de novo or were present initially and
      increased in aged/cooled blood: exon 20, exons 20 and 21 combined, exon 33, exon
      34, exon 37, exon 40, exon 45, exons 43 and 45 combined, part of exon 43, and the
      first codon of exon 12b. Some aberrant splice forms were undetectable when blood
      was drawn into Qiagen PAXgene tubes, rather than EDTA vacutainers, and we
      demonstrate how these aberrant splicing events are a potential pitfall for RNA
      based NF1 mutation characterization. The same reverse transcription/polymerase
      chain reaction strategy was used to screen for novel NF1 alternative splicing in
      Schwann cells and seven other tissues. Even though no Schwann-specific
      alternative exons were identified, we found minor novel splicing isoforms
      differentially expressed such as skips of exon 37 and exon 40. Skipping of exon
      43, part of exon 43, and the first codon of exon 12b were found in all tissues
      analyzed. These forms suggest greater tissue-based variability in the NF1 message
      than was previously thought and may indicate minor amounts of heterogeneity at
      the protein level.

PMID- 12073020
TI  - A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with
      hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription
      factors depends on a critical repeat length?
AB  - Hand-foot-genital syndrome (HFGS) is a dominantly inherited congenital
      malformation affecting the distal limbs and genitourinary tract. Here, we
      describe the phenotype and its molecular basis in a family that presented with
      HFGS. Genetic analysis revealed that the condition is caused by an 18-bp in-frame
      duplication within a cryptic trinucleotide repeat sequence encoding an 18-residue
      polyalanine tract in the homeoboxgene ( HOX) A13. This mutation expands the
      stretch with six extra alanine residues. Similar types of mutation (plus eight
      alanines) have recently been found in another HFGS family and also in the human
      HOXD13 gene (plus seven up to plus 14 residues) where it leads to synpolydactyly
      (SPD), a further congenital limb malformation rarely associated with genital
      abnormalities. As observed in our family, all the expanded tracts encoding
      polyalanine, either reported for HOXA13 or HOXD13, are quite stable when
      transmitted within affected families. Unlike disorders with unstable expansions
      of perfect trinucleotide repeats the molecular mechanism underlying these
      polyalanine expansions should be unequal crossing-over rather than replication
      slippage. The alanine tract elongation may prevent protein-protein interactions
      of the mutant HOXA13, thereby inducing a localized heterochrony in the sequence
      of distal limb and genitourinary development.

PMID- 12073022
TI  - Genome-wide linkage analysis assessing parent-of-origin effects in the
      inheritance of birth weight.
AB  - Family studies suggest that genetic variation may influence birth weight. We have
      assessed linkage of birth weight in a genome-wide scan in 269 Pima Indian
      siblings (334 sibling pairs, 92 families). As imprinting (expression of only a
      single copy of a gene depending on parent-of-origin), is commonly found in genes
      that affect fetal growth, we used a recently described modification of standard
      multipoint variance-component methods of linkage analysis of quantitative traits.
      This technique allows for comparison of linkage models that incorporate
      imprinting effects (in which the strength of linkage is expressed as LOD(IMP))
      and models where parent-of-origin effects are not included (LOD(EQ)). Where
      significant evidence of linkage was present, separate contributions of alleles
      derived from father (LOD(FA)) or mother (LOD(MO)) to the imprinting model were
      estimated. Significant evidence of linkage was found on chromosome 11 (at map
      position 88 cM, LOD(IMP)=3.4) with evidence for imprinting (imprinting model
      superior, P<0.001). In this region, birth weight was linked predominantly to
      paternally derived alleles (LOD(FA)=4.1, LOD(MO)=0.0). An imprinted gene on
      chromosome 11 may influence birth weight in the Pima population. This chromosome
      contains one of the two major known clusters of imprinted genes in the human
      genome, lending biological plausibility to our findings.

PMID- 12073023
TI  - Congenital fibrosis of the vertically acting extraocular muscles maps to the
      FEOM3 locus.
AB  - The diagnosis of congenital fibrosis of the extraocular muscles (CFEOM)
      encompasses several different inherited strabismus syndromes characterized by
      congenital restrictive ophthalmoplegia affecting extraocular muscles innervated
      by the oculomotor and/or trochlear nerves. The OMIM database
      (http://www.ncbi.nlm.nih.gov/Omim/) currently contains four familial CFEOM
      phenotypes: CFEOM1-3, which map to the FEOM1-3 loci (MIM 135600, 602078, 604361),
      respectively, and congenital fibrosis of the vertically acting extraocular
      muscles (MIM 600638), reported in a single family without a corresponding
      genotype. We have had the opportunity to study the reported family with this
      fourth phenotype and now demonstrate that their phenotype can be reclassified as
      CFEOM3 and that it maps to FEOM3, flanked by D16S498 to 16qter, with a maximum
      lod score of 6.0.

PMID- 12073024
TI  - Investigating the association between OPA1 polymorphisms and glaucoma: comparison
      between normal tension and high tension primary open angle glaucoma.
AB  - OPA1, the gene responsible for autosomal dominant optic atrophy, represents a
      good candidate gene for glaucoma, as there are similarities in the clinical
      phenotype and OPA1 is expressed in the optic nerve. Single nucleotide
      polymorphisms on intervening sequence (IVS) 8 of the OPA1gene (genotype IVS8+4
      C/T;+32T/C) were recently found to be strongly associated with normal tension
      glaucoma (NTG). In order to investigate whether this association exists in
      patients with high-tension glaucoma (HTG), 90 well-characterized HTG patients
      were examined for the presence of these OPA1polymorphisms by PCR amplification
      followed by bi-directional sequencing. Five out of 90 HTG subjects (5.6%; 95% CI
      1.8-12.5) were found to carry the OPA1 genotype IVS 8+4 C/T; +32 T/C, compared
      with 32/163 (19.6%; 95% CI 13.8-26.6) NTG subjects [chi(2)=9.2, P=0.002, OR 4.1
      (95% CI 1.6-11.1)], and 7/186 (3.8%; 95% CI 1.5-7.6) control subjects
      [chi(2)=0.47, P=0.49, OR 1.5 (95% CI 0.5-4.9)]. These results indicate that
      unlike NTG, the OPA1 genotype IVS8+4 C/T,+32T/C is not significantly associated
      with high-tension primary open angle glaucoma, and suggest genetic heterogeneity
      between the conditions.

PMID- 12073025
TI  - An Alu-mediated deletion at Xp11.23 leading to Wiskott-Aldrich syndrome.
AB  - Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by
      thrombocytopenia, eczema and immunodeficiency of varying severity. The WASP gene,
      mutations of which are responsible for the phenotype, maps to Xp11.23. We
      describe here a patient with a large deletion in the Xp11.23 region. The
      deletion, which totals 15.8 kb, begins downstream of DXS1696 and encompasses 13
      kb upstream of WASP and includes the distal and proximal promoters and exons 1-6.
      Analysis of the 5'-boundary region identified sequences missing in the Human
      Genome database and, as a result, the normal DNA sequence was revised to include
      743 bp of novel sequence (AF466616). The patient's upstream breakpoint was
      localized to an AluSg element within a highly repetitive DNA region containing
      other Alu elements. A 26-bp recombinogenic element is located downstream of the
      5' breakpoint. A 16-bp sequence just upstream of the 5' breakpoint shares close
      homology with the sequence that spans the 3' breakpoint in intron 6. A
      heptanucleotide of unknown origin, CAGGGGG, links the 5' and 3' breakpoints. To
      our knowledge this is the largest deletion in a WAS patient.

PMID- 12073029
TI  - Panzee, a copia-like retrotransposon from the grain legume, pigeonpea ( Cajanus
      cajan L.).
AB  - We report the isolation and characterization of a copia-like retrotransposon,
      Panzee, from pigeonpea ( Cajanus cajan). The 4947-bp Panzee element is AT rich
      (60%) and the integrated element is flanked by a target-site duplication of 5 bp.
      The structure of Panzee is that of a typical LTR-retrotransposon containing long
      terminal repeats (LTRs) which flank its internal region. The 5' LTR is 372 bp in
      length and the 3' LTR is 383 bp long. Both LTRs start with 5'-TG and end with CA
      3' and have 4-bp terminal inverted repeats. The internal region between the LTRs
      contains two priming sites for DNA synthesis: the first, a 12-bp primer binding
      site complementary to initiator methionyl tRNA, is located adjacent to the 3' end
      of the 5' LTR and the other, a 12-bp polypurine tract lies just upstream to the
      5' end of the 3' LTR. The putative polyprotein shows homology to all the proteins
      encoded by LTR retrotransposons, i.e. group-associated antigen ( gag),
      proteinase, endonuclease, reverse transcriptase (RT) and ribonuclease H (RNase
      H). However, the cloned copy of the element contains four frameshifts and a
      premature stop codon in its protein-coding domain. Genomic Southern hybridization
      experiments using probes derived from three different regions of the element show
      that Panzee or Panzee-related elements are present in high copy numbers in the
      pigeonpea genome. Analysis of transgenic tobacco plants containing the LTR:GUS
      construct shows that the 5' LTR of Panzee drives gene expression in this
      heterologous system in a tissue-specific manner. A phylogenetic tree constructed
      using reverse transcriptase sequences places Panzee in the copia group of
      retrotransposons.

PMID- 12073030
TI  - Characterization, heterologous expression and functional analysis of mevalonate
      diphosphate decarboxylase gene (MVD) of Candida albicans.
AB  - Mevalonate diphosphate decarboxylase (MVD) catalyzes the conversion of mevalonate
      diphosphate to isopentenyl diphosphate, a key building block for a large family
      of functionally important biomolecules. We have cloned the gene encoding MVD from
      Candida albicans, and report the first characterization of such a gene from an
      opportunistic fungal pathogen. Sequence analysis revealed that the MVD comprises
      362 amino acid residues with a predicted molecular weight of 39.5 kDa, sharing
      minimal identity with the human analogue. Analysis of the genomic sequence
      indicated that the coding frame is interrupted by a small intron of 51 bp.
      Southern analysis of genomic DNA demonstrated that MVD is a single-copy gene.
      Furthermore, Southern analysis of electrophoretic karyotypes of C. albicans
      obtained by pulsed-field gel electrophoresis showed that MVD is located on
      chromosome 1. Northern analysis revealed that the level of MVD expression is
      affected by (1) the carbon source in the growth medium, (2) the growth phase, and
      (3) the growth form of the fungus (yeast-like or hyphal). To demonstrate the
      biological function of C. albicans MVD, complementation experiments were carried
      out with an S. cerevisiae strain (erg19(ts)) that is temperature-sensitive for
      MVD activity. A single copy of the C. albicans MVD gene, under the control of the
      NOP1 promoter, was able fully to complement the erg19(ts) phenotype, and
      expression of the epitope-tagged C. albicans MVD was detectable by Western
      analysis. Furthermore, the low degree of sequence identity between C. albicans
      MVD and its human analogue raises the possibility that fungal-specific inhibitors
      can be developed for the enzyme. Thus, C. albicans MVD appears to be an
      interesting candidate that could be targeted for the development of anti-fungal
      agents.

PMID- 12073031
TI  - Mutational analysis of the Caenorhabditis elegans ankyrin gene unc-44
      demonstrates that the large spliceoform is critical for neural development.
AB  - In Caenorhabditis elegans, unc-44 mutations affect axonal outgrowth and guidance,
      leading to locomotory defects. The wild-type unc-44 gene encodes a family of
      ankyrin proteins, which, in addition to the conventional ankyrins, includes a
      novel ankyrin isoform with an extended C-terminal domain, referred to AO13
      ankyrin. Six spontaneous unc-44 mutations and their reversions were analyzed in
      order to localize regions critical for gene function. The q331::Tc1 and
      rh1013::Tc1 mutations were mapped to the portion of the gene encoding the
      conventional ankyrins, mn339 had an uncharacterized 2-kb insertion in the
      serine/threonine/glutamic acid/proline-rich (STEP) repeat block 5,
      st200::Tc5(variant) and rh1042::Tc1 were localized near the C-terminus, and mn259
      resulted from two Tc1 insertions, one in STEP block 6 and the other near the C
      terminus. Tc1 excisions in several revertants resulted either in the restoration
      of the wild-type sequence, or were associated with small in-frame deletions or
      insertions. Reversion of mn339 resulted in the net excision of 2463 bp of genomic
      DNA, including the region encoding parts of STEP blocks 5 and 6 and the
      intervening hydrophobic region. Interestingly, additional Tc1 insertions at a 5'
      exon/intron boundary were found in revertants of st200 and rh1042. Reversion of
      the st200::Tc5 mutation resulted in excision of the Tc5 element, and the
      insertion of two copies of Tc1 at different sites. The wild-type unc-44 gene
      produces multiple transcripts - shorter RNAs determined to be approximately 1,
      3.2, 5, 6, and 7 kb long, and two large transcripts estimated to be 22 and 26 kb
      in length. The largest transcripts were affected by all unc-44 mutations and are
      proposed to be essential for axonal outgrowth and guidance.

PMID- 12073032
TI  - Development of molecular markers for screening of Alnus nepalensis (D. Don)
      genotypes for the nitrogenase activity of actinorhizal root nodules.
AB  - Alnus nepalensis (D. Don), an alder species, is an actinorhizal tree found in the
      hilly regions of Eastern and Northeastern India. It is useful in the reclamation
      of wastelands generated by land slips, shifting agriculture and coal mining. To
      maximise the soil regeneration capacity of alder plantations, it would be useful
      to be able to select superior alder genotypes at the nursery level. Conventional
      methods of genotype screening are difficult to apply to open-pollinated forest
      trees. It would be beneficial if molecular markers could be developed for early
      screening. The study reported here was conducted to assess the feasibility of
      developing PCR-based AFLP and RFLP screening tools for the selection of superior
      genotypes of this valuable tree with respect to their ability to support
      efficient nitrogen-fixing root nodules. It was found that a multi-site strategy,
      including the chloroplast rrn operon and the nuclear rRNA genes, yielded
      promising results. A molecular marker for genotypes that support nodules with low
      nitrogenase activity was also identified.

PMID- 12073033
TI  - Phospholipase C interacts with Sgd1p and is required for expression of GPD1 and
      osmoresistance in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae PLC1 gene encodes a homolog of the delta isoform of
      mammalian phosphoinositide-specific phospholipase C. Cells deleted for PLC1 (
      plc1Delta) are viable, but display several phenotypes, including osmotic,
      temperature, and nocodazole sensitivity. We have used a two-hybrid screen to
      identify Plc1p-interacting proteins. One of the interacting proteins found was
      Sgd1p, a recently identified, essential, nuclear protein. The SGD1 gene was
      originally cloned by complementation of an osmostress-sensitive mutant. The Plc1p
      Sgd1p interaction was confirmed biochemically by affinity chromatography. SGD1
      interacts genetically with both PLC1 and HOG1 (which encodes an osmosensing
      mitogen-activated protein kinase). Overexpression of Sgd1p suppresses the
      temperature sensitivity of cells bearing the plc1-4 allele, and the double mutant
      strain plc1Delta sgd1-1 displays enhanced temperature and nocodazole sensitivity.
      The plc1Delta hog1Delta strain displays increased osmosensitivity, and has a
      synthetic defect in glycerol synthesis and the expression of GPD1 (which encodes
      the enzyme glycerol 3-phosphate dehydrogenase that is involved in glycerol
      biosynthesis), suggesting that Plc1p and Hog1p function in independent pathways.
      The hog1Delta sgd1-1 double mutant displays enhanced osmosensitivity relative to
      that of either single mutant. The triple mutant plc1Delta hog1Delta sgd1-1 is
      inviable, while the plc1Delta hog1Delta sgd1-2 strain grows extremely slowly and
      is more osmosensitive than the plc1Delta hog1Delta or hog1Delta sgd1-2 strain.
      These results are consistent with a model in which Plc1p and Hog1p function in
      parallel pathways affecting osmoregulation, and signals from both these pathways
      converge, at least partly, on Sgd1p.

PMID- 12073034
TI  - Molecular cloning, characterisation and expression of a manganese superoxide
      dismutase gene from peach (Prunus persica [L.] Batsch).
AB  - Two cDNA clones encoding mitochondrial manganese superoxide dismutases (MnSODs)
      from peach ( Prunus persica [L.] Batsch) were identified, which show homologies
      to several plant MnSODs. The amino acid sequence predicted from one full-length
      clone ( MnSOD1) showed the highest homology to an MnSOD from Nicotiana
      plumbaginifolia (94%) and included a 24-amino acid transit peptide typical of
      those used to target proteins to the mitochondria. A second, partial clone (
      MnSOD2) showed divergence from MnSOD1 in the 3' untranslated region. It could
      therefore derive from a second gene or from an allele of MnSOD1. Southern
      hybridisation analysis suggests the existence of two MnSOD genes in peach. SOD
      isoenzyme profiles, MnSOD1 expression and protein levels were studied in aerial
      vegetative tissues derived from plants of different ages and in adult plants
      during the seasonal cycle. Zymograms revealed at least two isoforms of MnSODs in
      pre-shooting vegetative buds and in developing fruits. Levels of MnSODs were
      lower in leaves derived from apical shoots of adult plants than in leaves derived
      from seedlings, basal shoots or in vitro propagated juvenile plants, which are
      considered as juvenile-like structures. The MnSOD1 transcript and protein
      followed the same pattern. The results suggest that the steady-state levels of
      MnSOD1 mRNA in leaves vary with both the ontogenetic stage and the growth rate of
      the tissues examined.

PMID- 12073035
TI  - Detection of gene-anchored amplification polymorphism (GAAP) in the vicinity of
      plant mitochondrial genes.
AB  - A simple, semi-automatable method was established for assessing polymorphism in
      plant mitochondrial genome. A set of 41 mitochondrial markers based on the
      published Arabidopsis thaliana sequence was developed in Brassicaceae using a
      gene-anchored amplification polymorphism (GAAP) strategy. PCR primers were
      selected based on conserved coding regions of mitochondrial genes and used to
      amplify the corresponding 5' and/or 3' non-coding flanking regions in order to
      maximise sequence variability between haplotypes. The variations in fragment size
      were analysed on a LiCor DNA sequencer, but the methodology is compatible with
      various sequencing systems using denaturing polyacrylamide gels. One advantage of
      the method is that GAAP products can be directly sequenced (without any cloning
      steps) through labelled M13 consensus sequences. Mitochondrial GAAP loci gave
      clear and simple patterns (one or two bands) that were easy to score and highly
      reproducible. Nearly all mitochondrial loci examined in A. thaliana were
      conserved within the Brassicaceae family, and half of the primers generated
      products when DNA from a distant species, Beta vulgaris (Chenopodiaceae), was
      used as template. The GAAP markers revealed low levels of polymorphism within
      species but exhibited a high level of polymorphism among genera and families. Our
      results showed some discrepancies with respect to the published mtDNA sequence of
      A. thaliana.

PMID- 12073036
TI  - Towards a genus-wide reference linkage map for Eucalyptus based exclusively on
      highly informative microsatellite markers.
AB  - A novel set of 50 highly polymorphic microsatellite markers were developed and
      mapped on existing RAPD framework maps of Eucalyptus grandis and E. urophylla.
      Together with the twenty previously developed microsatellite markers, these were
      used to align the existing maps for the two most commercially important
      Eucalyptus species in the tropics. Sixty-three microsatellite markers were placed
      on the E. grandis map in 11 linkage groups, and 53 on the E. urophylla map
      distributed in 10 linkage groups. Approximately 66% of the microsatellite markers
      segregated in a fully informative fashion, allowing the establishment of colinear
      syntenic linkage groups between the two maps. The 50 new microsatellite markers
      were highly informative, with an average of 14 alleles per locus, and average
      expected heterozygosity between 0.82 and 0.87. Furthermore, within the subgenus
      Symphyomyrtus, to which the vast majority of commercially important Eucalyptus
      species belong, these markers display on average 90% transportability. This set
      of 70 mapped microsatellite markers represents a significant step toward the
      development of a genus-wide reference linkage map for Eucalyptus. These highly
      multiallelic and transportable markers constitute a powerful tool for QTL
      discovery and validation, and can be used in directed searches for QTL allele
      variation across Eucalyptus pedigrees.

PMID- 12073037
TI  - SSP2, a sporulation-specific gene necessary for outer spore wall assembly in the
      yeast Saccharomyces cerevisiae.
AB  - Sporulation in yeast consists of two highly coordinated processes. First, a
      diploid cell that is heterozygous at the mating-type locus undergoes meiosis, in
      which one round of DNA replication is followed by two rounds of nuclear division.
      Second, the meiotic products are packaged into spore cells that remain within the
      mother cell. A large number of genes are induced specifically during sporulation,
      and their products carry out different sporulation-specific events. Expression of
      these sporulation-specific genes is controlled by several regulators which
      function at different stages of the sporulation program, resulting in a cascade
      of gene expression following induction of meiosis. Here we describe one
      sporulation-specific gene, SSP2, which is induced midway through meiosis. Ssp2
      shows significant homology to the predicted product of a hypothetical ORF in
      Candida albicans. Homozygous mutant ssp2 diploid cells fail to sporulate. In the
      mutant background, meiotic recombination and nuclear divisions remain normal;
      however, viability declines rapidly. Following meiosis, ssp2 cells form the
      prospore membrane, but fail to form the outer layer of the spore wall. The Ssp2
      protein localizes to the spore wall after meiosis II. In addition, the ssp2
      defect is also associated with delayed and reduced expression of late sporulation
      specific genes. Our results suggest that SSP2 function is required after meiosis
      II and during spore wall formation.

PMID- 12073038
TI  - Combinatorial variation in coding and promoter sequences of genes at the Tri
      locus in Pisum sativum accounts for variation in trypsin inhibitor activity in
      seeds.
AB  - Cultivars of Pisum sativum that differ with respect to the quantitative
      expression of trypsin/chymotrypsin inhibitor proteins in seeds have been examined
      in terms of the structure of the corresponding genes. The patterns of divergence
      in the promoter and coding sequences are described, and the divergence among
      these exploited for the development of facile DNA-based assays to distinguish
      genotypes. Quantitative effects on gene expression may be attributed to the
      overall gene complement and to particular promoter/coding sequence combinations,
      as well as to the existence of distinct active-site variants that ultimately
      influence protein activity. Electronic supplementary material to this paper can
      be obtained by using the Springer LINK server located at
      http://dx.doi.org/10.1007/s00438-002-0667-4.

PMID- 12073039
TI  - Efficient expression of the alpha-haemolysin determinant in the uropathogenic
      Escherichia coli strain 536 requires the leuX-encoded tRNA(5)(Leu).
AB  - The uropathogenic Escherichia coli strain 536 (O6:K15:H31) carries two alpha
      haemolysin determinants which are located on different pathogenicity islands (PAI
      I(536) and PAI II(536)). PAI II(536) is associated with the tRNA gene leuX. The
      leuX-encoded tRNA(5)(Leu) is required for the efficient expression of the hly
      determinants in strain 536. HlyA levels were reduced and secretion of the protein
      was delayed in the leuX-negative mutant strain 536Delta102. The lack of a
      functional tRNA(5)(Leu) resulted in a decrease in hly transcript levels in
      comparison to the wild-type strain. Analysis of several genes whose products are
      involved in the regulation of hly expression revealed that levels of RfaH and
      Hha, as well as the corresponding rfaH and hha transcripts, were higher in the
      leuX-negative background, whereas the expression of tolC and hns was not
      influenced by the leuX genotype. The analysis of hly transcript levels in hha
      deletion mutants of the E. coli strains 536 and 536Delta102 demonstrated that the
      increase in hha expression is partially responsible for the reduction in hly
      transcript levels in the leuX-negative background. These results demonstrate that
      the tRNA(5)(Leu) affects the expression of the alpha-haemolysin determinant at
      different levels in a regulatory cascade, and imply that, in addition to Hha, at
      least one further, as yet unidentified, regulatory factor must be involved in the
      regulation of hly transcription in the uropathogenic E. coli strain 536.

PMID- 12073040
TI  - Cloning and characterization of a cell cycle-regulated gene encoding
      topoisomerase I from Nicotiana tabacum that is inducible by light, low
      temperature and abscisic acid.
AB  - We have cloned a full-length 2874-bp cDNA coding for tobacco topoisomerase I,
      with an ORF of 2559 bp encoding a protein of 852 amino acids with a calculated
      molecular mass of 95 kDa and an estimated pI of 9.51. The deduced amino acid
      sequence shows homology to other eukaryotic topoisomerases I. Tobacco
      topoisomerase I was over-expressed in Escherichia coli, and the purified
      recombinant protein was found to relax both positively and negatively super
      coiled DNA in the absence of the divalent cation Mg(2+)and ATP. These
      characteristic features indicate that the tobacco enzyme is a type I
      topoisomerase. The recombinant protein could be phosphorylated at (a) threonine
      residue(s) by protein kinase C. However, phosphorylation did not cause any change
      in its enzymatic activity. The genomic organization of the topoisomerase I gene
      revealed the presence of 8 exons and 7 introns in the region corresponding to the
      ORF and one intron in the 3' UTR region. Transcript analysis using RT-PCR showed
      basal constitutive expression in all organs examined, and the gene was expressed
      at all stages of the cell cycle--but the level of expression increased during the
      G1-S phase. The transcript level also increased following exposure to light, low
      temperature stress and abscisic acid, a stress hormone.

PMID- 12073041
TI  - The beta-propeller protein YxaL increases the processivity of the PcrA helicase.
AB  - The DNA helicase PcrA is found in gram-positive bacteria and belongs to the
      superfamily 1 (SF1) of helicases, together with Rep and UvrD helicases from
      Escherichia coli. These helicases have been extensively studied in vitro and
      their mode of unwinding are well characterised. However, little is known about
      the putative cellular partners of such helicases. To identify PcrA-interacting
      factors, PcrA was used as a bait in a genome-wide yeast two-hybrid screen of a
      Bacillus subtilis library. Three proteins with unknown functions - YxaL, YwhK and
      YerB - were found to interact specifically with PcrA. The yxaL gene was cloned,
      the product was overexpressed and purified, and its effect on the PcrA activity
      was investigated in vitro. YxaL enhanced the processivity of the PcrA helicase. A
      comparison of the amino acid sequence of YxaL with other proteins from data banks
      suggests that YxaL belongs to a family of proteins with a repeated domain, which
      adopt a typical three-dimensional structure designated as a "beta-propeller".
      This raises the possibility that YxaL acts as a connector protein between PcrA
      and another cellular component.

PMID- 12073042
TI  - The upr-1 gene encodes a catalytic subunit of the DNA polymerase zeta which is
      involved in damage-induced mutagenesis in Neurospora crassa.
AB  - The upr-1 mutant was one of the first mutagen-sensitive mutants to be isolated in
      Neurospora crassa. However, the function of the upr-1 gene has not yet been
      elucidated, although some genetic and biochemical data have been accumulated. In
      order to clone the upr-1 gene, we performed a chromosome walk from the mat locus,
      the closest genetic marker to upr-1 for which a molecular probe was available,
      towards the centromere, and a chromosomal contig of about 300-400 kb was
      constructed. Some of these clones complemented the temperature sensitivity of the
      un-16 mutation, which is located between mat and upr-1. The un-16 gene was
      sequenced, and localized in the MIPS Neurospora crassa genome database. We then
      searched the regions flanking un-16 for homologs of known DNA repair genes, and
      found a gene homologous to the REV3 gene of budding yeast. The phenotype of the
      upr-1 mutant is similar to that of the yeast rev3 mutant. An ncrev3 mutant
      carrying mutations in the N. crassa REV3 homolog was constructed using the RIP
      (repeat-induced point mutation) process. The spectrum of mutagen sensitivity of
      the ncrev3 mutant was similar to that of the upr-1 mutant. Complementation tests
      between the upr-1 and ncrev3 mutations indicated that the upr-1 gene is in fact
      identical to the ncrev3 gene. To clarify the role of the upr-1 gene in DNA
      repair, the frequency of MMS and 4NQO-induced mutations was assayed using the ad
      8 reversion test. The upr-1 mutant was about 10 times less sensitive to both
      chemicals than the wild type. The expression level of the upr-1 gene is increased
      on exposure to UV irradiation in the uvs-2 and mus-8 mutants, which belong to
      postreplication repair group, as well as in the wild type. All these results
      suggest that the product of the upr-1 gene functions in damage-induced
      mutagenesis and DNA translesion synthesis in N. crassa.

PMID- 12073043
TI  - The Pseudomonas aeruginosa hemA promoter is regulated by Anr, Dnr, NarL and
      Integration Host Factor.
AB  - Pseudomonas aeruginosa forms most of its heme under anaerobic denitrifying
      conditions. To study the regulation of the hemA gene, which codes for the first
      enzyme of heme biosynthesis in P. aeruginosa, a lacZ reporter gene fusion was
      constructed. Expression of lacZ under the control of the hemA promoter was found
      to be increased by 2.8-fold under anaerobic conditions in the presence of the
      alternative electron acceptor nitrate, relative to the level observed under
      aerobic growth conditions. Anaerobic fermentative growth or the presence of
      nitrite did not affect the lacZ expression. The genes encoding the oxygen sensor
      protein Anr, the redox regulator Dnr, the nitrate regulator NarL and the DNA
      bending Integration Host Factor (IHF) are all required for the cooperative
      anaerobic induction of the hemA promoter hemAp (1). Potential binding sites for
      these regulatory proteins were identified by site-directed mutagenesis of the
      promoter fused to the reporter gene. The mode of regulation of P. aeruginosa hemA
      differs significantly from that described for the hemA gene of Escherichia coli K
      12.

PMID- 12073044
TI  - Evidence for horizontal transfer of the LTR retrotransposon mdg3, which lacks an
      env gene.
AB  - Horizontal (interspecific) transfer is regarded as a possible strategy for the
      propagation of transposable elements through evolutionary time. To date, however,
      conclusive evidence that transposable elements are capable of horizontal transfer
      from one species to another has been limited to class II or DNA-type elements. We
      tested the possibility of such transfer for several Drosophila melanogaster LTR
      retrotransposons of the gypsy group in an experiment in which D. melanogaster and
      D. virilis somatic cell lines were used as donor and recipient cells,
      respectively. This approach was chosen in light of the high levels of LTR
      retrotransposon amplification and expression observed in cultured D. melanogaster
      cells. In the course of the experiment, parallel analysis for mdg1, mdg3, 17.6,
      297, 412 and B104/roo retrotransposons was performed to detect their presence in
      the genome of recipient cells. Only the mdg3 retrotransposon, which lacks an env
      gene, was found to be transmitted into recipient cells. This model, based on the
      use of cultured cells, is a promising system for further investigating the
      mechanisms of LTR retrotransposon transfer.

PMID- 12073045
TI  - Photomorphogenesis in Phycomyces: differential display of gene expression by PCR
      with arbitrary primers.
AB  - The zygomycete fungus Phycomyces blakesleeanus develops two types of fruiting
      bodies of very different size, macrophores and microphores. Blue light stimulates
      macrophorogenesis and inhibits microphorogenesis. I have adapted a method based
      on the polymerase chain reaction with arbitrary primers to investigate the role
      of differential gene expression during photophorogenesis in Phycomyces. Several
      cDNAs for genes induced in vegetative mycelium have been observed, but only one
      gene induced by blue light has been detected. I have demonstrated the feasibility
      of this approach by the isolation of a cDNA segment for the heat-shock protein
      HSP100 that is induced by blue light at the onset of sporangiophore development.
      The heat-shock protein HSP100 is an ATP-binding protein that has the ability to
      disassemble protein complexes. In plants, the gene for HSP100 is induced by
      light. The cDNA segment for HSP100 obtained from Phycomyces is 686 bp long and
      the predicted amino acid sequence contains one of the ATP-binding sites.

PMID- 12073046
TI  - Immunohistochemical study of the expression of cell cycle regulating proteins at
      different stages of bladder cancer.
AB  - PURPOSE: The cell cycle is known to be deregulated in cancer. We therefore
      analyzed the expression of the cell cycle related proteins p21, p27, p16, Rb, and
      L-myc by immunohistochemical staining of bladder tumors. METHODS: The tissue
      material consisted of bladder tumors from three groups of patients; group 1, 23
      patients with recurrent stage Ta (non-invasive) tumors; group 2, 22 patients
      presenting at their first admission with T2-4 (muscle invasive) tumors; group 3,
      24 patients who experienced disease progression from Ta or T1 (invasive in
      connective tissue) to a higher stage. By immunohistochemical staining the protein
      expression was compared to allelic deletions of the corresponding genes. The
      allelic deletions were detected by PCR-based microsatellite analyses. RESULTS: We
      detected a significant reduction in the expression levels of the cell cycle
      related proteins p21(waf1) ( P=0.002), p27(kip1) ( P=0.03), Rb ( P=0.00002), and
      L-myc ( P=0.00000007) in muscle invasive tumors compared to noninvasive tumors.
      Tumors presenting as muscle invasive at first diagnosis had significantly lower
      levels of p16/CDKN2A ( P=0.01) when compared to muscle invasive tumors that
      followed Ta or T1 precursor lesions. We found no general correlation between
      allelic deletion of a gene and its immunohistochemical protein expression,
      indicating that the remaining allele may be capable of encoding a normal or even
      increased protein level. CONCLUSIONS: Our results support the hypothesis that
      bladder tumors with invasion at first diagnosis differ from those in which
      invasion follow superficial tumors. This difference is reflected as a different
      level in cell cycle related protein expression. The data also indicate that
      allelic deletions of cell cycle related genes do not correlate with an altered
      level of protein expression.

PMID- 12073047
TI  - Expression of survivin in primary glioblastomas.
AB  - PURPOSE: Studies in several tumour types have suggested that the inappropriate
      expression of the novel inhibitor of apoptosis protein survivin may play a key
      role in tumourigenesis. This study presents the first immunohistochemical
      examination of survivin expression in glioblastomas. METHOD: The cohort consisted
      of 39 ethnic Chinese patients diagnosed with primary glioblastoma multiforme.
      Samples were archival paraffin-embedded blocks. Concomitant with examination for
      survivin expression, samples were also examined for over-expression of the p53
      protein as well as for evidence of apoptotic cells via the terminal
      deoxynucleotide transferease (TdT) mediated nick end labelling (TUNEL) technique.
      RESULTS: Results showed that survivin was expressed in nearly 80% (31/39) of
      samples. Over-expression of moderate or high levels of survivin was correlated
      with the absence of apoptotic cells ( P=0.03). Expression of survivin and p53 was
      found to be significantly related ( P=0.037), and 70% (27/39) of tumours showed
      co-ordinate expression of p53 and survivin. CONCLUSION: Given that p53 over
      expression in primary glioblastomas is predominantly detected in the absence of
      mutations of the gene, and that both survivin and p53 are regulated at the level
      of the protein by the same ubiquitin-proteosome degradation pathway, these
      results suggest that primary glioblastomas may occur as a result of a failure of
      appropriate protein degradation regulation.

PMID- 12073048
TI  - Expression of cyclin A in endometrial adenocarcinoma and its correlation with
      proliferative activity and clinicopathological variables.
AB  - PURPOSE: Cyclin A is known as an S- and G2-M phase regulatory protein and its
      abnormal expression has been reportedly implicated in cellular proliferation.
      This study was designed to investigate the correlation of cyclin A expression
      with tumorigenesis of the endometrium and clinicopathological variables. METHODS:
      Immunohistochemical staining using labeled streptavidin-biotin complex was
      performed on formalin-fixed, paraffin-embedded tissue of normal endometrium (15
      cases), endometrial hyperplasia (23 cases), and endometrial adenocarcinoma
      (endometrioid type) (112 cases). RESULTS: Immunohistochemistry showed that the
      nuclei of the cells were positive for cyclin A. In normal endometrium, only
      proliferative phase was focally positive for cyclin A. Cyclin A was also positive
      for endometrial hyperplasia. Its expression in hyperplasia was significantly more
      frequent than that of proliferative phase and less than that of endometrioid
      adenocarcinoma. The labeling index (LI) of cyclin A in endometrioid
      adenocarcinoma was 16.3+/-6.9 in well-differentiated, 18.3+/-8.8 in moderately
      differentiated, and 30.2+/-11.8 in poorly differentiated adenocarcinoma,
      respectively. Cyclin A expression increased significantly more in high
      histological grades. The area of squamous metaplasia in endometrioid
      adenocarcinoma was negative for cyclin A. The LI of cyclin A was positively
      correlated with that of Ki-67 and cyclin-dependent kinase 2. Cyclin A expression
      was significantly associated with carcinoma without coexisting endometrial
      hyperplasia and lymphovascular space involvement (LVSI), but not with FIGO stage,
      myometrial invasion, lymph node metastasis, estrogen receptor, progesterone
      receptor, and menopause as well as recurrence. CONCLUSIONS: Cyclin A expression
      was involved in the progression to malignancy of the endometrium and was
      correlated with proliferative activity and prognostic features including
      histological grade, without coexisting endometrial hyperplasia and LVSI.

PMID- 12073049
TI  - Phase I clinical and pharmacokinetic study of combination chemotherapy with
      topotecan and ifosfamide in patients with progressive or relapsed solid tumors.
AB  - PURPOSE: Topotecan and ifosfamide are effective in the treatment of various solid
      tumors. Up to the time of this study, the two drugs have been combined just once
      (Smith et al. 1998). Due to its hematotoxicity, topotecan has been used
      predominantly within monochemotherapy protocols. However, the combination of
      topotecan and alkylating agents is supra-additive in many preclinical models.
      This phase-I trial was primarily performed to evaluate the maximum tolerable dose
      (MTD) and dose-limiting toxicity (DLT) of a combination chemotherapy with
      topotecan and ifosfamide using a 5-day schedule. A secondary goal was to estimate
      the response rate in a group of heavily pretreated patients with advanced solid
      tumors. METHODS: The pharmacokinetics of topotecan were preliminarily determined
      in some of the patients. A total of 12 patients (three female/nine male), median
      age 49 years (range 19-69), 11 with prior chemotherapy, received a total of 24
      courses of chemotherapy at three dose-levels of topotecan. Ifosfamide was
      administered by intravenous infusion over 3 h immediately followed by a 30-min
      infusion of topotecan. Mesna (3 x 300 mg x m(2) x day) was given routinely during
      chemotherapy as a uroprotector. G-CSF (filgrastim) was permitted only in cases of
      febrile neutropenia (FN). RESULTS: The major toxicity was non-hematologic; severe
      liver and renal toxicity were observed in three out of 11 patients. Two treatment
      related deaths occurred. No clinical remissions occurred in 11 evaluable
      patients. The pharmacokinetics of topotecan were relatively similar in our
      patients and supported findings in recent literature. The MTD of this combination
      was defined at dose-level 2 (1.0 mg/m(2) of topotecan and 750 mg/m(2) of
      ifosfamide). CONCLUSIONS: Further trials should not exceed this dose. The
      pharmacological causes for the pronounced toxicity have to be clarified.

PMID- 12073050
TI  - Estrogen receptor beta is expressed in human stomach adenocarcinoma.
AB  - PURPOSE: In stomach adenocarcinoma, the role of the hormonal receptor, estrogen
      receptor (ER), has been controversial. Recently, a new estrogen receptor, called
      estrogen receptor beta (ER beta), was found to be expressed in various tissues
      including normal gastrointestinal tract. In this paper, the expression of ER beta
      in stomach adenocarcinomas has been investigated for the first time, specifically
      in signet ring cell adenocarcinomas, together with surrounding non-cancerous
      tissues. METHODS: By immunohistochemistry the expression of ER alpha and beta was
      studied in 29 stomach adenocarcinomas, ten signet ring cell adenocarcinomas, and
      19 other adenocarcinomas. Western blotting was performed to examine the
      immunohistochemical result. Statistical studies (Student's t test and chi(2)
      test) explored the relation between the immunohistochemical result and
      clinicopathological characteristics. RESULTS: All 29 adenocarcinomas, including
      the signet ring cell ones, demonstrated clear ER beta nucleus staining.
      Lymphocytes, venous endothelial cells, smooth muscle, and non-cancerous stomach
      glands also showed strong ER beta staining, while no staining was observed in the
      immunohistochemistry of ER alpha. Western blotting showed equivalent ER beta
      protein levels in cancerous and non-cancerous tissues, which was consistent with
      the results of immunohistochemical staining. Among signet ring cell
      adenocarcinomas of the stomach, cytoplasm were stained in addition to nuclei,
      specifically in patients under the age of 40 years. CONCLUSIONS: Our results
      imply that the effects of estrogen in stomach cancer, as well as those in normal
      stomach, may be mediated by ER beta, and that the role of ER beta may differ by
      the subtype of stomach adenocarcinoma - specifically signet ring cell
      adenocarcinomas and other ones - although large scale samples are needed to
      confirm these findings.

PMID- 12073051
TI  - Comparing whole body (18)F-2-deoxyglucose positron emission tomography and
      technetium-99m methylene diphosphonate bone scan to detect bone metastases in
      patients with breast cancer.
AB  - PURPOSE: At present, bone metastases are usually assessed using conventional
      technetium-99m methylene diphosphonate whole-body bone scan, which has a high
      sensitivity but a poor specificity. However, positron emission tomography with
      (18)F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved
      specificity. We attempted to evaluate the usefulness of FDG-PET for detecting
      bone metastases in breast cancer and to compare FDG-PET results with bone scan
      findings. PATIENTS: The study group comprised 48 patients with biopsy-proven
      breast cancer and suspected of having bone metastases who underwent bone scan and
      FDG-PET to detect the bone metastases. The final diagnosis of bone metastases was
      established by operative, histopathological findings or during a clinical follow
      up longer than 1 year by additional radiographs or following FDG-PET/bone scan
      findings showing progressive widespread bone lesions. RESULTS: A total of 127
      bone lesions including 105 metastatic and 22 benign bone lesions found by either
      FDG-PET or bone scan were evaluated. Using FDG-PET, 100 metastatic and 20 benign
      bone lesions were accurately diagnosed, and using bone scan 98 metastatic and 2
      benign bone lesions were accurately diagnosed. The diagnostic sensitivity and
      accuracy of FDG-PET were 95.2% and 94.5%, and of bone scan were 93.3% and 78.7%,
      respectively. CONCLUSIONS: Our findings suggest that FDG-PET shows a similar
      sensitivity and a better accuracy than bone scan for detecting bone metastases in
      patients with breast cancer.

PMID- 12073052
TI  - Detection of disseminated tumor cells in patients with cervical cancer.
AB  - PURPOSE: Detection of disseminated tumor cells in a cohort of patients presenting
      the entire spectrum of invasive cervical cancer. METHODS: Disseminated tumor
      cells were detected in blood samples taken at different times during surgery or
      in bone marrow aspirates by a HPV type-specific nested PCR enzyme immunoassay (n
      PCR-EIA). A group of 24 patients with HPV-positive cervical cancers representing
      early and late stages were evaluated, and 15 patients with breast cancer and
      without HPV-related genital disease served as controls. RESULTS: Disseminated
      tumor cells were detected in blood samples and/or bone marrow aspirates of 6 of
      24 patients. A significant association was found between detectable disseminated
      tumor cells and recurrent disease ( P=0.013) and between disseminated tumor cells
      and survival of the patients ( P=0.0054). There was also a clear association
      between the presence of disseminated tumor cells and tumor size and/or positive
      lymph node status which, however, was not statistically significant. There was no
      evidence of increased shedding of tumor cells during surgery. CONCLUSION:
      Detection of disseminated tumor cells in blood or bone marrow may prove to be of
      prognostic value, particularly for early-stage cervical cancers.

PMID- 12073053
TI  - Coexpression of Ets-1 and p53 in oral carcinomas is associated with P
      glycoprotein expression and poor prognosis.
AB  - PURPOSE: To determine the association between the expression of P-gp with Ets-1
      and p53 proteins in oral squamous cell carcinomas (SCCs). MATERIALS AND METHODS:
      Immunohistochemical analysis of Ets-1, P-glycoprotein (P-gp), and p53 proteins
      was carried out in 40 formalin-fixed, paraffin-embedded tissue sections from oral
      SCCs using specific antibodies for these proteins. RESULTS: Expression of Ets-1
      protein was observed in 27/40 (68%) cases, P-gp was overexpressed in 27/40 (68%)
      cases, and p53 accumulation was observed in 26/40 (65%) cases. Twenty-two of 27
      (82%) SCCs showed concomitant overexpression of Ets-1 and P-gp underpinning an
      association between the expression of these two proteins ( P=0.007). Twenty-one
      of 27 (78%) Ets-1 overexpressing oral SCCs showed accumulation of p53 protein (
      P=0.015). Nineteen of the 27 (70%) P-gp expressing tumours showed p53
      accumulation. Concomitant Ets-1 and P-gp overexpression was significantly
      associated with poor prognosis ( P=0.002). In multivariate analysis using Cox's
      proportional hazards model, P-glycoprotein emerged as the most significant
      adverse predictor of disease-free survival (HR=6.2, P=0.003). The hallmark of the
      study was the significant association between the expression of Ets-1, P-gp, and
      p53 proteins in oral SCCs and their association with poor prognosis. Oral cancer
      patients showing concomitant expression of Ets-1, P-gp, and p53 proteins had
      shorter disease-free survival (median time of no recurrence=18 months) and worst
      prognosis ( P=0.001) as compared to the cases overexpressing any of these
      proteins. CONCLUSION: Concomitant expression of Ets-1, P-gp, and p53 proteins
      adversely affects the clinical outcome in oral SCCs.

PMID- 12073054
TI  - Intraocular pressure sensor: where are we - where will we go?

PMID- 12073055
TI  - Side effects after radiotherapy of age-related macular degeneration with the
      Nijmegen technique.
AB  - BACKGROUND: In a randomized trial concerning radiotherapy for age-related macular
      degeneration, fluorescein angiograms were taken of controls and patients. In this
      study the frequency of side effects in eyes receiving radiotherapy with the
      Nijmegen technique is compared with the findings in the eyes of controls.
      METHODS: Patients receiving treatment were irradiated by two isocentric photon
      beams in four fractions of 6 Gy that were directed to the macular area at 30
      degrees and -30 degrees with regard to the optical axis. The most recent
      fluorescein angiograms of the randomized eyes (32 treated and 31 control eyes)
      were scored by two independent researchers, using a scoring form with nine
      features of radiation retinopathy: nonperfusion, macular edema, microaneurysms,
      retinal hemorrhages, cotton-wool spots, perifoveal telangiectasis, vascular
      sheathing, retinal neovascularization, and radiation-associated choroidal
      neovasculopathy. The results were graded as: no retinopathy (grade 0), mild
      retinopathy (grade 1), moderate retinopathy (grade 2), and severe retinopathy
      (grade 3). RESULTS: In the treated group 6 patients (18.8%) were grade 1, 10
      patients (31.2%) were grade 2 and 7 patients (21.9%) were grade 3. In the control
      group 9 patients (29.0%) were grade 1, 11 patients (35.5%)were grade 2 and 2
      patients (6.5%) were grade 3. There were no patients with retinal
      neovascularization. CONCLUSION: With the Nijmegen technique a relatively high
      dose of radiation can be applied to a small retinal area. In only a minority of
      cases does some evidence of radiation retinopathy occur.

PMID- 12073056
TI  - Change in retinal arterial blood flow in the contralateral eye of retinal vein
      occlusion during glucose tolerance test.
AB  - PURPOSE: To investigate the changes in retinal blood flow (RBF) during a 75-g
      oral glucose tolerance test in the contralateral eye of patients with retinal
      branch vein occlusion (BRVO). METHODS: Seventeen patients with BRVO were
      included. None had a known history of diabetes mellitus. The blood velocity and
      vessel diameter of the upper temporal retinal artery in the contralateral eye
      were measured using laser Doppler velocimetry with an eye-tracking system before
      and 1, 2, and 3 h after oral intake of 75 g glucose. Blood sugar, systemic blood
      pressure, and intraocular pressure were monitored. Eleven healthy volunteers were
      examined similarly as control. RESULTS: Nine patients (53%) with BRVO had an
      abnormal pattern on the glucose tolerance test. RBF significantly increased at 1,
      2, and 3 h in eight patients with normal glucose tolerance. The changes in RBF
      primarily resulted from changes in vessel diameter; the blood velocity did not
      change significantly. The nine patients with impaired glucose tolerance or
      diabetes mellitus had a RBF pattern that was significantly lower at 2 and 3 h
      than those with normal oral glucose tolerance. In the control group, all 11
      volunteers showed the same increases in RBF at 2 and 3 h as the BRVO patients
      with a normal glucose pattern. CONCLUSION: A relatively high number of patients
      with BRVO had an abnormal pattern on glucose tolerance testing. Glucose intake
      increased RBF in BRVO patients without diabetes and in healthy volunteers. The
      RBF response may differ between subjects with diabetes and those without
      diabetes.

PMID- 12073057
TI  - First evidence of an endogenous Spiroplasma sp. infection in humans manifesting
      as unilateral cataract associated with anterior uveitis in a premature baby.
AB  - PURPOSE: To elucidate a previously unknown aetiology of rapidly progressive
      unilateral cataract in a premature baby associated with severe anterior uveitis.
      METHODS: The lens and vitreous material were saved as part of a special protocol
      in a 4-month-old premature baby at the time of pars plana lensectomy with
      anterior vitrectomy. We performed (1) microbiological cultures to detect viable
      bacterial and fungal organisms; (2) PCR reaction to viral, bacterial and fungal
      agents; (3) transmission electron microscopy (TEM). In addition, serological
      examinations were performed for HSV-1 and -2, CMV, VZV and Mycoplasmainfection.
      RESULTS: PCR detected Spiroplasma sp.; TEM confirmed the presence of Spiroplasma
      within the lens fibres. Serological testing and microbiological cultures of the
      vitreous and lens were negative. CONCLUSION: Endogenous Spiroplasma infection in
      a premature baby may manifest as rapidly progressive acquired unilateral cataract
      with anterior uveitis. Beyond this, Spiroplasma infection has never been reported
      to occur naturally in vertebrates, although experimentally Spiroplasma mirum
      produces panophthalmitis associated with cataract in a wide range of rodents and
      in chicks. In acquired infantile cataract with inflammatory signs, PCR and TEM
      should be performed in the lensectomy/vitrectomy material to detect infectious
      agents not evident on routine laboratory and microbiological examinations.

PMID- 12073058
TI  - Polypoidal choroidal vasculopathy with large vascular network.
AB  - PURPOSE: To report characteristics of polypoidal choroidal vasculopathy (PCV) of
      large vascular networks that expand across the retinal vascular arcade. METHODS:
      Among 60 consecutive eyes diagnosed as having PCV by fluorescein and indocyanine
      green (ICG) angiography, 12 eyes (9 patients) showed large lesions. The clinical
      and angiographic features of these 12 eyes were studied retrospectively. RESULTS:
      Cases of large PCV typically showed dilated network vessels, which spread
      radially, and multiple polypoidal dilations at the end of the network vessels.
      Most of the polypoidal dilations formed clusters resembling bunches of grapes and
      caused large serous and/or hemorrhagic pigment epithelial detachments (PEDs).
      Among the 12 eyes, 5 showed rapid expansion of the lesions and became large PCVs
      within 3-24 months. In these eyes, ICG angiography revealed mesh-like choroidal
      vessels beneath the retinal pigment epithelium. CONCLUSION: PCV with a large
      vascular network that expands across the vascular arcade is not uncommon. Some of
      these cases seems to have characteristics of choroidal neovascularization rather
      than choroidal vasculopathy. It is not easy to distinguish such cases from
      exudative age-related macular degeneration even though they showed typical
      findings of PCV on ICG angiography.

PMID- 12073059
TI  - Detecting the inner and outer borders of the retinal nerve fiber layer using
      optical coherence tomography.
AB  - BACKGROUND: The purpose of this study was to develop a new algorithm to detect
      the inner and outer borders of the retinal nerve fiber layer (RNFL) using optical
      coherence tomography (OCT). METHODS: A program featuring a new algorithm was
      developed using a commercially available software development environment. The
      algorithm searches for peaks on each sampling line instead of applying
      conventional thresholding techniques. All circular peripapillary OCT images
      obtained at the New York Eye and Ear Infirmary from October 1996 to December 2000
      were analyzed using the new and the commercially available algorithms. RESULTS:
      Four hundred one images of 98 patients were analyzed. The detection error rate
      (defined as number of scans with five consecutive sampling lines with disrupted
      RNFL borders) was significantly lower with the new algorithm (25/401 images,
      6.2%) than with the commercially available algorithm (70/401 images, 17.5%)
      (P=0.018, chi-square). CONCLUSION: The new algorithm improved the ability of OCT
      to detect the borders of the RNFL.

PMID- 12073060
TI  - Nocturnal blood pressure reduction: effect on retrobulbar hemodynamics in
      glaucoma.
AB  - BACKGROUND: Several studies suggest that nocturnal reductions in systemic blood
      pressure (BP) may be associated with onset or progression of glaucomatous optic
      neuropathy. The present study aimed to find out whether reductions in nocturnal
      BP are linked to retrobulbar blood flow perturbations in glaucoma patients.
      METHODS: Fifteen patients with non-progressing glaucoma and 15 controls were
      studied in the evening ("baseline") and then at a point of significantly reduced
      arterial BP during the night. Flow velocities were measured with color Doppler
      imaging (CDI) in the ophthalmic, central retinal, and nasal and temporal short
      posterior ciliary arteries, and with transcranial Doppler (TCD) in the middle
      cerebral artery. BP, corrected for posture, was monitored throughout the night.
      RESULTS: Maximal posture-corrected nocturnal BP reductions were similar in
      patients and controls. The reductions were about 10% for each group ( P<0.01). At
      baseline, patients had lower peak systolic and end-diastolic velocity ( P<0.05)
      in the short posterior ciliary arteries than controls. Flow velocities in these
      arteries remained constant in glaucoma patients, while controls showed
      significant declines. Patients and controls demonstrated blood flow velocities
      unchanged from baseline in the central retinal, ophthalmic, and middle cerebral
      arteries during nocturnal BP reduction. CONCLUSIONS: In patients with non
      progressing glaucoma there was no evidence of cerebral or retrobulbar hemodynamic
      abnormalities during nocturnal BP dips. Posterior ciliary arterial blood flow
      velocities were similar in glaucoma patients and controls during nocturnal BP
      dips.

PMID- 12073061
TI  - Effect of 0.005% latanoprost once daily on intraocular pressure in glaucomatous
      patients not adequately controlled by beta-blockers twice daily: a 3-year follow
      up. Experience and incidence of side effects in a prospective study on 76
      patients.
AB  - PURPOSE: To assess the efficacy and side effects of 0.005% latanoprost once daily
      during 3 years of treatment in glaucomatous patients in whom intraocular pressure
      (IOP) was not adequately controlled by beta-blockers twice daily. METHODS: An
      unmasked prospective study was performed on 76 glaucomatous patients (145 eyes)
      treated with 0.005% latanoprost at bedtime, after a 21-day wash-out period from
      beta-blockers. IOP measurement and visual field examination were recorded over
      the follow-up period. RESULTS: Latanoprost significantly reduced IOP from 26.5+/
      6.6 mmHg (mean +/- SD) to 17.4+/-2.7 mmHg after 36 months of treatment in 48
      patients (63.1%), who completed the trial. Twenty-eight patients (36.8%)
      discontinued the therapy. In 12 patients (15.8%) the treatment did not obtain a
      satisfactory target IOP. In two subjects (2.6%), despite the IOP reduction,
      visual field damage progressed. The remaining 10 patients (13.1%) discontinued
      the treatment because of the following side effects: microfollicular
      conjunctivitis (seven cases); severe oedema of conjunctiva and eyelids (one
      case); corneal punctate erosion (one case); cystoid macular oedema (one case). No
      flare or pigmentary changes of iris and eyelash were observed. CONCLUSION:
      Latanoprost 0.005% once daily significantly reduces IOP in the majority of
      glaucomatous patients uncontrolled by beta-blockers. The reduction of IOP was
      statistically significant during 3 years of follow-up, confirming the clinical
      efficacy of this compound. The ocular side effects requiring cessation of therapy
      were mainly allergic reactions. The most severe adverse effects were one case of
      corneal punctate erosion and one case of cystoid macular oedema in a pseudophakic
      patient.

PMID- 12073062
TI  - Corneal endothelial cell loss after nonmechanical penetrating keratoplasty
      depends on diagnosis: a regression analysis.
AB  - PURPOSE: To assess the impact of diagnosis on corneal endothelial cell loss after
      nonmechanical penetrating keratoplasty (PK) with regression models. METHODS: Five
      hundred eighty-nine eyes [273 with keratoconus (group I; PK only), 187 with
      Fuchs' endothelial dystrophy (group II; 77 PK only and 110 triple procedures) and
      129 with bullous keratopathy (group III; 115 pseudophakic and 14 aphakic eyes)]
      were included in this prospective study. The time course of the endothelial cell
      density after PK was assessed by specular microscopy. Endothelial cell density
      was analyzed in cross-sectional fashion at 6 and 24 months follow-up and in
      longitudinal manner (follow-up 2.4+/-1.8 years) with linear and exponential
      regression models (minimizing the residuum between observed and predicted
      endothelial cell count). Donor age, post-mortem time, storage time and ratio of
      organ-cultured to short-term-preserved donor corneas did not differ significantly
      between groups of patients. RESULTS: In a cross section, endothelial cell density
      in group I / group II / group III decreased from 1,959+/-499 / 1,524+/-528 /
      1,526+/-670 cells/mm(2)to 1,617+/-553 / 1,222+/-520 / 1,063+/-384 cells/mm(2)
      (P=0.06 / 0.04 / 0.005). Endothelial cell count was significantly higher in group
      I than in group II (P=0.048) and significantly higher in group II than in group
      III (P=0.01) at 24 months. In the linear regression model, cell count decreased
      in group I / group II / group III by 136+/-465 / 241+/-374 / 421+/-484 cells
      annually. In the exponential regression model, cell count decreased in group I /
      group II / group III by 2.9+/-28.0% / 11.2+/-21.8% / 19.3+/-29.4% annually. Cell
      loss was highly significantly lower in group I than in group II ( P<0.0001) and
      highly significantly lower in group II than in group III (P<0.0001). CONCLUSION:
      Endothelial cell loss seems to be least pronounced after PK in keratoconus
      (2.9%), followed by Fuchs' dystrophy (11.2%) and bullous keratopathy (19.3%).
      These differences between diagnoses indicate migration of endothelial cells along
      a density gradient after PK.

PMID- 12073063
TI  - The effects of exposure to a 1.5-tesla magnetic field on intravitreous metallic
      foreign bodies in rabbits.
AB  - BACKGROUND: The study was performed to determine (1) whether intravitreous
      ferromagnetic foreign bodies (FBs) are sufficiently mobile in a magnetic field to
      induce acute injury in vivo, and (2) whether the length of time from implantation
      of the intravitreous FB affects mobility. METHODS: A 3 mm x 0.72 mm magnetic FB
      (MFB) and a non-magnetic metallic FB (NMFB) of similar dimensions were surgically
      implanted into the right and left eyes, respectively, of 20 New Zealand white
      rabbits. On days 0 (FB implantation) and 30, all rabbits underwent computed
      tomography (CT) prior to and immediately following exposure to a 1.5-tesla (T)
      magnetic field. Pre- and post-magnetic field CT image FB angles and distances,
      together with ophthalmic examinations, were used to assess FB mobility. Rabbits
      were killed at 31 days. The globes were processed for light microscopy (LM) and
      scanning electron microscopy (SEM). RESULTS: Angle measurements revealed that the
      MFBs developed significant angular motion and were scattered more widely than
      NMFBs on the day of FB implantation and 30 days later, although the angular
      motion and scatter of MFBs were less on day 30. There were no significant
      differences among distance measurements for MFBs or NMFBs on or between days 0
      and 30. Throughout the 30-day study, ophthalmic examinations revealed dorso
      ventral FB movement and focal vitreous degeneration and retinal hemorrhage within
      both MFB- and NMFB-containing globes. Mild vitreous hemorrhage was noted around a
      NMFB. Focal retinal degeneration was confirmed by LM ( n=1 MFB). SEM revealed
      intravitreous erythrocytes and spindle cells adjacent to all FBs examined.
      CONCLUSIONS: (1) Angle measurements show that MFBs are significantly mobile when
      exposed to a 1.5-T magnetic field on the same day as FB implantation and 30 days
      later. (2) Angular mobility of MFBs is less at 30 days. (3) Magnetic field
      exposure did not induce ocular injury in MFB-containing globes. (4) Intravitreous
      metallic FB retention induces ocular pathologic changes.

PMID- 12073065
TI  - Antiproliferative effect of mycophenolate mofetil on cultured human Tenon
      fibroblasts.
AB  - BACKGROUND: Wound healing after glaucoma filtering surgery is often complicated
      by exaggerated scarring of the subconjunctival Tenon's layer. Therefore,
      antiproliferatives are commonly employed. The immunosuppressive drug
      mycophenolate mofetil (MMF) is used to prevent graft rejection after kidney or
      liver transplantation. The effect is mediated by inhibition of lymphocyte
      proliferation. In this study we investigated the effect of MMF on human Tenon
      fibroblast proliferation in cell culture. METHODS: Human Tenon fibroblasts (HTF)
      were cultivated with 10% fetal calf serum. Cells were incubated with MMF
      concentrations of 0.1 microM to 3000 microM for up to 20 days. In a second set of
      experiments HTF were incubated for 10 min only in MMF solutions. Cell counts were
      performed to evaluate the proliferation rate. The proliferation was also assessed
      by Ki67 staining. Morphological changes were documented by vimentin staining.
      RESULTS: Growth inhibition of HTF by MMF was concentration dependent. IC(50) was
      0.85+/-0.05 microM for 6 days of incubation. Brief exposure to MMF leads to a
      reversible growth arrest for up to 14 days with concentrations of 1000 microM or
      higher. Ki67 staining confirmed the concentration dependent proliferation rate.
      CONCLUSION: MMF has a concentration-dependent antiproliferative effect on HTF
      without any detected cytotoxicity in the applied concentration range. Brief
      incubation also leads to a growth arrest; therefore, intraoperative MMF
      application might prevent exaggerated scarring after glaucoma filtering surgery.

PMID- 12073064
TI  - Iris pigment epithelial cells transplanted into the vitreous accumulate at the
      optic nerve head.
AB  - BACKGROUND: Iris pigment epithelial (IPE) cells have mainly been investigated in
      the past for their proposed potential to rescue or even replace degenerated
      retinal pigment epithelial (RPE) cells after subretinal transplantation in
      patients with age-related macular degeneration (AMD). More recent reports have
      characterised the IPE cell as a potent source of trophic factors and cytokines.
      In our study we investigated the spatial distribution of IPE cells that were
      injected into the vitreous instead of being injected subretinally. METHODS: IPE
      cells from Long Evans rats were isolated and injected into the vitreous cavity of
      Wistar rats without preculturing. Free melanin granules were injected into the
      vitreous in the same manner. After a period of 2 months, eyes were prepared for
      histological analysis. Localisation of the injected IPE cells was defined by
      topographical mapping of the analysed sections. RESULTS: PVR was not observed in
      any eye. In 8 of 10 injected eyes, IPE cells had accumulated in the prepapillary
      region. In 2 of 10 eyes, no IPE cells could be detected. The injected melanin
      granules also accumulated at the optic nerve head, indicating that this is most
      likely a passive process. In sections of the papillary region containing retinal
      vessels, the IPE cells seemed to have migrated into the superficial tissue of the
      optic nerve head. CONCLUSION: Our results demonstrate a way to access the optic
      nerve head easily and securely without the danger of damaging its fragile
      structure. This could have important implications for new therapeutic strategies
      in ocular neurodegenerative diseases like glaucoma. New prospects in gene therapy
      will require further characterisation of the potential of the IPE cell to produce
      neuroprotective trophic factors at the optic nerve head.

PMID- 12073066
TI  - Long-term results of penetrating keratoplasty using a single or double running
      suture technique.
AB  - BACKGROUND: Corneal astigmatism changes after penetrating keratoplasty (PK) with
      single running suture (SRS) or double running suture (DRS) were evaluated in this
      prospective randomized study. METHODS: Sixty-eight consecutive eyes underwent PK:
      35 received a SRS and 33 an anti-torque DRS using the same Hanna Suction System.
      All sutures were removed between 12 and 20 months after surgery. RESULTS: Within
      the first month after PK, a statistically significant difference was noted, with
      a lower mean value of astigmatism for the DRS group. The final mean postoperative
      videokeratographic astigmatism was 3.51+/-1.93 and 3.42+/-1.94 in the SRS and DRS
      group respectively (36 months' follow-up). CONCLUSIONS: Although the final
      astigmatism was about the same in the two suture groups, the DRS seems to lead to
      faster restoration of visual function due to early stability.

PMID- 12073068
TI  - The pathology and molecular biology of anal intraepithelial neoplasia:
      comparisons with cervical and vulvar intraepithelial carcinoma.
AB  - BACKGROUND: Anal intraepithelial neoplasia (AIN) is a well-described pathological
      precursor of invasive squamous cell carcinoma which has recently been detected
      with increasing frequency in immunocompromised patients, particularly those with
      seropositivity for human immunodeficiency virus (HIV). The epidemiology and
      natural history of this entity is somewhat unclear, since the overall prevalence
      in the HIV seronegative population is unknown. DISCUSSION: There is a clear
      etiological association between AIN and high-risk human papillomavirus (HPV)
      subtype infection although there is great variability in HPV DNA detection of
      cytological and histological material in these patients. It appears that there is
      an antigen-specific hyporesponsiveness by cytotoxic lymphocytes against HPV
      peptide sequences or recombinant proteins encoded by oncogenic HPV subtypes in
      these patients, which is dependent upon the stage of their HIV-associated
      disease. Although the molecular biology of AIN and cervical or vulvar
      intraepithelial neoplasia are comparable, in AIN there is less significance of
      tumor suppressor gene mutations, proto-oncogenic growth factor activation, and
      genomic instability. CONCLUSION: Current concepts in the epidemiology and
      etiology of AIN are discussed, as well as its immunological response in the HIV
      positive population, drawing parallels where possible between other HPV-related
      preinvasive disorders, and concluding with a suggested management protocol

PMID- 12073069
TI  - Inflammatory bowel disease and pregnancy.
AB  - The peak age ranges for pregnancy and inflammatory bowel disease (IBD) coincide,
      and many women develop IBD during their reproductive years. This contribution
      reviews the major studies on the subject, and is sub-divided into two broad
      considerations: the effects of the disease on fertility, pregnancy and other
      factors related to the puerperium, and, conversely, the effects of pregnancy and
      childbirth on the disease: its natural history and recent surgical treatment
      options, namely pouch anatomy and function. A systematic review of the literature
      from 1950 to the present was undertaken using Medline and the keywords
      inflammatory bowel disease and pregnancy.

PMID- 12073070
TI  - Abrogated lymphocyte infiltration and lowered CD14 in dextran sulfate induced
      colitis in mice treated with p65 antisense oligonucleotides.
AB  - BACKGROUND AND AIMS: Dextran sulfate sodium (DSS) induced colitis exhibits a
      predominantly NF-kappaB dependent proinflammatory cytokine profile and shares
      similarities with human inflammatory bowel disease (IBD). Lamina propria
      macrophages of IBD patients display elevated levels of NF-kappaB p65. Knowing the
      role of NF-kappaB in IBD, we investigated the beneficial cellular mechanisms
      underlying the lasting effect of a single p65 antisense treatment in DSS-colitis
      mice. METHODS: One local dose of p65 antisense oligonucleotides was administered
      in DSS colitis mice. Ten days later the mice were killed and examined at cellular
      and biochemical levels. The level of p65 in lamina propria cells was determined
      by electrophoretic mobility shift assay and by intracellular immunofluorescent
      staining of nuclear p65 levels, using laser scanning cytometer. RESULTS: FACS
      analysis demonstrated a considerable drop in infiltrating lymphocytes and a
      drastic reduction in CD14+ cells in mice treated with p65 antisense
      oligonucleotides. Moreover, abrogation of inflammation extended all the way to
      the cecum in treated mice. Treatment was correlated with decreased DNA binding
      activity of NF-kappaB. CONCLUSION: Our data strongly support a model in which p65
      antisense treatment possesses the capacity to disrupt the pathogenic autocrine
      loop propagated by NF-kappaB at the chronic phase of IBD.

PMID- 12073071
TI  - HLA-DRB1*1502 confers susceptibility to ulcerative colitis, but is negatively
      associated with its intractability: a Korean study.
AB  - BACKGROUND AND AIMS: Several studies have documented the high incidence of
      several HLA class II alleles in Japanese patients with ulcerative colitis (UC).
      Although the characteristics of the HLA system in Koreans are quite similar to
      those in the Japanese, it is not clear whether the HLA pattern in Korean UC is
      similar to that in Japanese UC. We investigated an association between HLA class
      II genes and UC patients and the clinical meaning of these genes in Korea.
      PATIENTS AND METHODS: Unrelated Korean patients with UC ( n=70) and ethnically
      matched unrelated controls ( n=182) were genotyped for HLA-DR by PCR followed by
      reverse hybridization using sequence-specific oligonucleotide probes. The
      clinical characteristics of the patients were analyzed with regard to anti
      neutrophil cytoplasmic antibody (ANCA) status and total colectomy for
      intractability. RESULTS: HLA-DR2 and DRB1*1502 were found significantly more
      frequently in patients (42.9% and 21.4%) than controls (20.3% and 5.5%).
      DRB1*1502 was more frequent in p-ANCA-positive (5/23) than in p-ANCA-negative
      (1/11) patients. Total colectomy for intractability was performed more commonly
      in patients without DRB1*1502 (14/55) than in those with it (0/15). CONCLUSIONS:
      Our data are consistent with those of Japanese studies in that DR2 and DRB1*1502
      are positively associated with UC patients. In contrast to the Japanese study,
      however, our results demonstrates that DRB1*1502 is negatively associated with
      the risk of colectomy in Korean patients with UC.

PMID- 12073072
TI  - Investigation of HLA-DPA1 genotypes as predictors of inflammatory bowel disease
      in the German, South African, and South Korean populations.
AB  - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is a polygenic disorder, as
      demonstrated by epidemiological evidence, genetic linkage, and the identification
      of the first susceptibility gene, NOD2. Genetic linkage analysis has identified
      and replicated several genomic regions as locations for susceptibility genes,
      including chromosome 6p (termed IBD3). The HLA-DP genes play an important role in
      antigen presentation and are located within the chromosome 6p linkage region.
      PATIENTS AND METHODS: We investigated HLA-DPA1 as a positional and functional
      candidate gene for IBD using 249 German multiplex IBD families, 174 unrelated
      German controls, 48 monoplex families from a mixed South African population, 87
      IBD patients, and 71 controls from a South Korean sample. Polymorphisms in exon 2
      at amino acid positions 31, 37-38 and 50 were genotyped using direct sequencing.
      Analyses were performed using chi(2) statistics, multipoint transmission
      disequilibrium test and nonparametric linkage analysis. RESULTS: A marginally
      significant association for Crohn's disease was detected in the German family
      cohort for DPA1*02021. This finding was not replicated in ulcerative colitis or
      any of the other populations. CONCLUSION: HLA-DPA1 is not a major determinant of
      IBD risk in any of the three populations. The transmission distortion observed in
      the German cohort may indicate an extended haplotype, suggesting another disease
      relevant gene in the vicinity of HLA-DPA.

PMID- 12073073
TI  - Glutamine distribution in patients with ulcerative colitis and in patients with
      familial adenomatous polyposis coli before and after restorative proctocolectomy.
AB  - BACKGROUND AND AIMS: Restorative proctocolectomy with construction of an ileoanal
      pouch (IPAA) is the surgical treatment of choice for patients with ulcerative
      colitis (UC) or familial adenomatous polyposis (FAP). This procedure imposes an
      essential change in function on the terminal ileal mucosa and pouch mucosa.
      Glutamine is one of the major nutrients for the small-bowel mucosa; it is
      metabolized into glutamate and subsequently alanine in the human enterocyte. In a
      prospective clinical trial we compared glutamine distribution in patients with UC
      to that in patients with FAP before and after restorative proctocolectomy.
      METHODS AND PATIENTS: Concentrations of glutamine, glutamate, and alanine were
      measured pre- and postoperatively in the terminal ileal mucosa, pouch mucosa,
      skeletal muscle and venous blood of patients undergoing IPAA for UC or FAP.
      Healthy individuals served as controls for skeletal muscle glutamine
      concentration. RESULTS: After IPAA the glutamine concentration in UC patients was
      decreased in skeletal muscle. In the mucosa glutamine remained unaltered while
      glutamate and alanine concentrations increased. In plasma the glutamine
      concentration increased, the glutamate level fell, and the alanine level
      increased. In FAP patients the glutamine level was unchanged in skeletal muscle
      after IPAA. In mucosa the glutamine level did not change, but glutamate and
      alanine increased. In plasma the glutamine level remained unaltered, glutamate
      decreased, and alanine increased. CONCLUSION: Patients with UC or FAP before
      surgical therapy do not suffer from glutamine depletion. IPAA resulted in changes
      in the distribution of glutamine and its metabolites in skeletal muscle, plasma,
      and ileal pouch mucosa, particularly in patients with UC. Further studies should
      investigate whether characteristics in the glutamine distribution have any impact
      for the long-term outcome after IPAA.

PMID- 12073074
TI  - Evaluation of myenteric ganglion cells and interstitial cells of Cajal in
      patients with chronic idiopathic constipation.
AB  - BACKGROUND AND AIMS: The aim of this study was to identify myenteric ganglion
      cells (MGC) and interstitial cells of Cajal (ICC) from the total colectomy
      specimen in patients with chronic idiopathic constipation. PATIENTS AND METHODS:
      Fourteen patients who had severe, intractable, long-standing (mean: 14 years)
      constipation underwent subtotal colectomy and ileorectal anastomosis. All
      resected specimens were investigated with hematoxylin and eosin (H&E) and
      immunohistochemical staining with anti-neurofilament monoclonal antibody
      NF(2)F(11) for MGC, and c-kit antibody for ICC. The numbers of MGC and ICC were
      counted for ascending (AC), descending (DC), and sigmoid colon (SC). We compared
      these data with those from ten control specimens. RESULTS: The number of MGC was
      significantly smaller in AC and DC of the constipated group than in the control
      group. Interestingly, SC contained a similar number of MGC. The two staining
      methods were equally effective for identifying MGC. The total ICC number in the
      constipated group was markedly lower in every segment. Most anatomical layers of
      the colon, including the submucosal border, circular muscle, and longitudinal
      muscle, revealed a similar tendency. However, in the myenteric plexus area there
      was no significant difference between the two groups. CONCLUSION: A quantitative
      decrease in MGC and ICC appears to be implicated in chronic idiopathic
      constipation.

PMID- 12073076
TI  - Subjective and functional results after replacement of the stomach with an
      ileocecal segment: a prospective study of 20 patients.
AB  - BACKGROUND AND AIMS: The optimal reconstruction procedure after gastrectomy is
      still a matter of debate. The ileocecal interpositional graft offers an excellent
      reservoir capacity, the preservation of duodenal passage, and a natural
      antireflux barrier (ileocecal sphincter). PATIENTS AND METHODS: We prospectively
      analyzed the quality-of-life outcome in 20 patients undergoing ileocecal
      interpositional graft (13 subdiaphragmatic reconstruction, 7 intrathoracic
      reconstruction) after gastrectomy in a University Hospital and a Canton Hospital
      (mean follow-up 6 months), operative and postoperative morbidity, body weight,
      reflux, and dumping symptoms. In a smaller series of nine patients we performed
      functional tests such as gastric emptying measurements, glucose tolerance tests,
      and manometry of the gastric substitute. RESULTS: The mean gastrointestinal
      quality-of-life index in the subdiaphragmatic reconstruction group 114, and that
      in the intrathoracic reconstruction group was 106. Mild reflux and dumping
      symptoms were noted by no patients in the former group and by two of seven
      patients in the latter. In the smaller series of nine patients gastric emptying
      time was faster in the intrathoracic group, but no difference in plasma glucose
      level was found between the two groups. CONCLUSIONS: Reconstruction after
      gastrectomy with an ileocecal interpositional graft achieves good quality of life
      with an acceptable morbidity. The technique seems to reduce the occurrence of
      postoperative reflux and dumping symptoms.

PMID- 12073075
TI  - Modelling the economic impact of managing a chronic anal fissure with a
      proprietary formulation of nitroglycerin (Rectogesic) compared to lateral
      internal sphincterotomy in the United Kingdom.
AB  - BACKGROUND AND AIMS: This study estimated the economic impact of using a
      proprietary formulation of 0.2% nitroglycerin (GTN) ointment (Rectogesic)
      compared with lateral internal sphincterotomy in the treatment of a chronic anal
      fissure in the United Kingdom (UK), from the perspective of the National Health
      Service (NHS). PATIENTS AND METHODS: Clinical and surgical outcomes attributable
      to managing a chronic anal fissure were obtained from published literature,
      supplemented with information about resource utilisation derived from interviews
      with a panel of colorectal surgeons and general practitioners. Using this
      information, a decision tree modelling the management of a chronic anal fissure
      by a colorectal surgeon was constructed. Unit resource costs at 1999/2000 prices
      were applied to the resource utilisation estimates in the model to estimate the
      expected NHS cost of managing a chronic anal fissure. Consensus on the
      information contained within the model was reached at a meeting with an expert
      panel comprising five of the interviewees and one other colorectal surgeon.
      RESULTS: The expected NHS cost of a colorectal surgeon initially managing a
      chronic anal fissure with GTN was estimated to be pound616, compared to pound840
      when a lateral internal sphincterotomy is the first-line treatment. Moreover, the
      expected probability of successful healing following initial treatment with
      either intervention is 99-100%, taking into account all subsequent treatments.
      CONCLUSION: The initial use of GTN compared to lateral internal sphincterotomy to
      treat a chronic anal fissure affords a potential cost reduction to the NHS of
      pound224 per patient without any loss in effectiveness. Hence, GTN is potentially
      a cost-effective first-line treatment strategy for the management of a chronic
      anal fissure.

PMID- 12073077
TI  - Toxic megacolon due to Salmonella: a case report and review of the literature.
AB  - BACKGROUND AND AIMS: Salmonella colitis is an unusual cause of toxic megacolon.
      We provide an overview of this condition and report a single case. PATIENTS AND
      METHODS: A 62-year-old man underwent subtotal colectomy with ileostomy formation
      for toxic megacolon due to Salmonella enteritidis phage type 4 colitis, followed
      by reversal with an ileorectal anastomosis. RESULTS: Twenty-seven cases have been
      described in the literature. These were first treated conservatively, with
      antibiotics and systemic/local steroids, and some proceded to surgery.
      CONCLUSION: Salmonella is a rare cause of toxic megacolon, but it can behave
      opportunistically in patients with ulcerative colitis. S. enteritidis phage type
      4 is typically transmitted via raw or uncooked eggs in most cases of
      salmonellosis attributed to this organism. The disease is rapidly progressive,
      and death may ensue due to septicaemia and/or perforation. Toxic megacolon is
      treated aggressively, initially medically, with high-dose steroids and attention
      to fluid balance, ulcerative colitis being the usual working diagnosis. Once
      Salmonella is cultured, appropriate antibiotics are commenced. Non-surgical
      decompression may be appropriate in some cases, but early surgical intervention
      is required for failed response to these measures or rapid deterioration in the
      patient's condition. Following initial surgery - often subtotal colectomy and
      ileostomy formation - continuity may be restored. For most patients with
      ulcerative colitis ileal pouch anal anastomosis is the operation of choice, but
      ileorectal anastomosis may be safely performed for Salmonella-induced toxic
      megacolon. Prevention is better than cure, and therefore health education needs
      to reinforce avoidance of use of raw or uncooked eggs.

PMID- 12073078
TI  - Epidermoid cyst of the cecum of an elderly man with no previous history of
      surgery: a case report and review of literature.
AB  - BACKGROUND: Pure, benign epidermoid cysts of the abdominal viscera are rare.
      There have been only four reports of epidermoid cysts of the cecum in the
      literature, two following appendectomies and attributed to the surgical
      procedure, and two in female patients, raising the possibility of dermoid cysts
      related to the ovaries. PATIENTS AND METHODS: We report the first case of
      epidermoid cyst of the cecum in an elderly man with no previous history of trauma
      or surgery, detected by computed tomography as an incidental finding of
      extraluminal cystic cecal mass. It was treated by partial colectomy.
      Pathologically the cyst was roughly spherical, extending from and expanding the
      serosal surface of the cecum with no communication through the muscularis wall.
      Histologically the inner lining of the cyst was composed of benign, mature,
      keratinized, stratified squamous epithelium with a well formed granular layer. No
      calcification, hair, teeth, or bone elements was detected. RESULTS: The
      interesting finding in our case is the unusual anatomical location and the age
      and sex of the patient. The patient had no history of any abdominal surgical
      procedures. The most likely explanation for the presence and development of an
      epidermoid cyst in this location is the result of an aberrant ectodermal
      implantation during embryogenesis. CONCLUSION: Awareness of the possibility of
      the presence of epidermoid cysts in this area with distinctive radiological
      findings consistent with a well circumscribed benign cyst should be considered in
      the differential diagnosis of cysts within the abdomen.

PMID- 12073079
TI  - Colour in the eyes of insects.
AB  - Many insect species have darkly coloured eyes, but distinct colours or patterns
      are frequently featured. A number of exemplary cases of flies and butterflies are
      discussed to illustrate our present knowledge of the physical basis of eye
      colours, their functional background, and the implications for insect colour
      vision. The screening pigments in the pigment cells commonly determine the eye
      colour. The red screening pigments of fly eyes and the dorsal eye regions of
      dragonflies allow stray light to photochemically restore photoconverted visual
      pigments. A similar role is played by yellow pigment granules inside the
      photoreceptor cells which function as a light-controlling pupil. Most insect eyes
      contain black screening pigments which prevent stray light to produce background
      noise in the photoreceptors. The eyes of tabanid flies are marked by strong
      metallic colours, due to multilayers in the corneal facet lenses. The corneal
      multilayers in the gold-green eyes of the deer fly Chrysops relictus reduce the
      lens transmission in the orange-green, thus narrowing the sensitivity spectrum of
      photoreceptors having a green absorbing rhodopsin. The tapetum in the eyes of
      butterflies probably enhances the spectral sensitivity of proximal long
      wavelength photoreceptors. Pigment granules lining the rhabdom fine-tune the
      sensitivity spectra.

PMID- 12073080
TI  - The cord stretch receptors in the abdominal nerve cord of the crayfish Cherax
      destructor: physiology and relationships.
AB  - The physiology and relationships of tonic cord stretch receptor neurons in the
      crayfish Cherax destructor were examined with intracellular and extracellular
      recording. Cord stretch evoked slow depolarisations leading to action potentials
      in tonic cord stretch receptor neurons. Intermittent post-synaptic potentials
      were also seen in cord stretch receptor neurons but were not the primary cause of
      the action potentials. Cord stretch still evoked action potentials in cord
      stretch receptor neurons when all synaptic activity, monitored at another known
      chemical synapse, was blocked using high [Mg(2+)] and low [Ca(2+)] in the bath.
      One source of facilitating excitatory post-synaptic potentials in the cord
      stretch receptor neurons was from mechanosensory hairs on the dorsal abdominal
      surface. Tonic cord stretch receptor neuron activity was associated with an
      increase in the activity of the abdominal slow extensor inhibitor motor neuron
      and at least one abdominal flexor excitor motor neuron in its segment, and
      reduced activity in the abdominal slow flexor inhibitor motor neuron. Activation
      of individual cord stretch receptor neurons produced a local resistance reflex.
      Cord stretch, activating many receptors, produced several other outcomes. One was
      the "extensor state" described in earlier literature. The tonic cord stretch
      receptor neurons of Cherax destructor appear to be stretch-sensitive interneurons
      that receive inputs from other elements of the abdominal control system and
      mediate polysynaptic reflex activity in postural motor neurons.

PMID- 12073082
TI  - Spatial control of rhabdom shedding in the lateral eye of the American horseshoe
      crab, Limulus polyphemus.
AB  - Membrane leaves the rhabdom of Limulusphotoreceptors either by transient shedding
      at dawn or throughout the day by light-driven shedding. We examined whether the
      light trigger for transient shedding and the light drive for light-driven
      shedding are localized properties of the illuminated photoreceptors or whether
      they are an array property of the retina. Four experiments were conducted during
      which the lateral eye was exposed to one of a variety of different illumination
      patterns for a day, fixed, dissected and cut into serial frozen sections.
      Immunocytochemistry with different antibodies to Limulus opsin and arrestin
      revealed the results of the two processes in a distinguishable way. Eyes
      stimulated with whole-eye illumination had both types of shedding or just light
      driven shedding when transient shedding was blocked by cutting the optic nerve.
      Eyes exposed to whole-eye darkness had neither type of shedding. However, when
      only half of an eye was exposed to light, the dark half had the same kinds of
      shedding as the lighted half. We conclude that the signals to trigger or drive
      shedding must be communicated laterally from illuminated ommatidia to
      unilluminated ommatidia. Rhabdom shedding is an array property.

PMID- 12073081
TI  - Differential parallel processing of olfactory information in the honeybee, Apis
      mellifera L.
AB  - Two distinct neuronal pathways connect the first olfactory neuropil, the antennal
      lobe, with higher integration areas, such as the mushroom bodies, via antennal
      lobe projection neurons. Intracellular recordings were used to address the
      question whether neuroanatomical features affect odor-coding properties. We found
      that neurons in the median antennocerebral tract code odors by latency
      differences or specific inhibitory phases in combination with excitatory phases,
      have a more specific activity profile for different odors and convey the
      information with a delay. The neurons of the lateral antennocerebral tract code
      odors by spike rate differences, have a broader activity profile for different
      odors, and convey the information quickly. Thus, rather preliminary information
      about the olfactory stimulus first reaches the mushroom bodies and the lateral
      horn via neurons of the lateral antennocerebral tract and subsequently odor
      information becomes more specified by activities of neurons of the median
      antennocerebral tract. We conclude that this neuroanatomical feature is not
      related to the distinction between different odors, but rather reflects a dual
      coding of the same odor stimuli by two different neuronal strategies focusing
      different properties of the same stimulus.

PMID- 12073083
TI  - Muscarinic receptors modulate intracellular Ca(2+) concentration in hyaline cells
      of the chicken basilar papilla.
AB  - Nonsensory hyaline cells border the sensory epithelium of the auditory end-organ
      (basilar papilla) in birds and reptiles. Their innervation by cochlear
      cholinergic efferent fibers and the presence of contractile proteins suggest that
      hyaline cells may actively regulate basilar membrane mechanics. The cholinergic
      pharmacology of hyaline cells was studied by measuring the intracellular calcium
      concentration ([Ca(2+)](i)) of fura-2-loaded cells in the chicken cochlea in
      vitro. Superfusion of the cholinergic agonist carbachol produced a dose-dependent
      increase in hyaline cell [Ca(2+)](i) (EC(50)=1.05 micromol l(-1)) and small
      responses in short hair cells. Calcium increases in hyaline cells were evoked by
      the muscarinic agonists oxotremorine (10 micromol l(-1)) and muscarine (100
      micromol l(-1)) whereas nicotine (100 micromol l(-1), 200 micromol l(-1)) was
      without effect. Carbachol-evoked responses were blocked by the muscarinic
      antagonist atropine (>or=10(-13) mol l(-1)) and were unaffected by the nicotinic
      antagonists d-tubocurare (100 micromol l(-1), 1 mmol l(-1)) and hexamethonium
      (100 micromol l(-1)). Responses persisted in the absence of extracellular Ca(2+)
      and were abolished by thapsigargin (1 micromol l(-1)). These results indicate
      that the cholinergic-stimulated increase in hyaline cell [Ca(2+)](i) is due to a
      muscarinic-mediated release of Ca(2+) from intracellular stores. This is the
      first evidence that hyaline cells possess a muscarinic receptor whose activation
      causes mobilization of intracellular Ca(2+).

PMID- 12073084
TI  - Electrophysiological properties of spinal motoneurons in the adult turtle.
AB  - The purpose of this study was to develop a scheme for classifying turtle
      motoneurons, such that their properties could be compared to those of other
      vertebrate species, including, in particular, the cat. A 130-cell sample of
      turtle motoneurons was provisionally classified into four groups (1-4) on the
      basis of a cluster analysis of the cells' intracellularly recorded input
      resistance, rheobase, and slope of their stimulus current-spike frequency
      relation. These measurements, using sharp microelectrodes and an in vitro spinal
      cord slice preparation, were particularly robust. It is argued that the cat
      counterpart of our turtle type 1, 2, and 3 motoneurons innervate slow-twitch
      muscle fibers, fast-twitch-oxidative fibers, and fast-twitch-glycolytic fibers,
      respectively. Our turtle type 4 motoneuron is thought analogous to a particularly
      high-threshold cat and human cell that innervates highly fatigable fast-twitch
      muscle fibers in both species. Our turtle type 1 category may include cells that
      innervate non-twitch muscle fibers, which are found in other non-mammalian
      vertebrates. To advance comparative spinal cord neurobiology, the present results
      invite comparison to the motoneurons of other vertebrate species, which have yet
      to be subjected to similar or other classification procedures.

PMID- 12073085
TI  - Evidence for shear-induced increase in membrane fluidity in the dinoflagellate
      Lingulodinium polyedrum.
AB  - Fluid shear stress has been demonstrated to affect the structure and function of
      various cell types. In mammalian cells, it was hypothesized that shear-induced
      membrane fluidization leads to activation of heterotrimetric G-proteins. The
      purpose of this study was to determine if a similar mechanism exists in the
      dinoflagellate Lingulodinium polyedrum, a single-celled eukaryotic aquatic
      organism that bioluminesces under shear stress. Membrane fluidity changes in L.
      polyedrum were monitored using the molecular rotor 9-(dicyanovinyl)-julolidine,
      whose fluorescence intensity changes inversely with membrane fluidity. Dual
      staining with 9-(dicyanovinyl)-julolidine and the membrane dye 1-(4
      trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate indicates
      membrane localization. Subjecting L. polyedrum cells to increasing shear stress
      reversibly decreased 9-(dicyanovinyl)-julolidine fluorescence, while
      autofluorescence of the cytoplasmic chlorophyll did not change. The relationship
      between shear stress (0.63 Pa, 1.25 Pa, 1.88 Pa, and 2.5 Pa) and membrane
      fluidity changes was linear and dose-dependent with a 12% increase in fluidity at
      2.5 Pa. To further explore this mechanism a membrane fluidizing agent, dimethyl
      sulfoxide was added. Dimethyl sulfoxide decreased 9-(dicyanovinyl)-julolidine
      emission by 41+/-15% and elicited a dose-dependent bioluminescent response at
      concentrations of 0.2%, 0.5%, 1.0%, and 1.25%. This study demonstrates a link
      between fluid shear stress and membrane fluidity, and suggests that the membrane
      is an important flow mechanosensor of dinoflagellates.

PMID- 12073087
TI  - Genome-wide expression analysis of genes affected by amino acid sensor Ssy1p in
      Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae Ssy1p is a membrane protein which senses extracellular
      amino acids and controls the expression of certain amino acid permease genes.
      Analysis by DNA micro-array newly identified DIP5 and MUP1 as the positive
      targets and CAN1, PUT4 and GAP1 as the negative targets under Ssy1p control.
      Interestingly, the effect of ssy1 deletion was not restricted to amino acid
      permease genes: the expression of nitrogen catabolite repression (NCR)-sensitive
      genes and methionine-biosynthesizing genes ( MET genes) was derepressed by the
      deletion of SSY1. Constitutive overexpression of the genes for glutamine permease
      ( GNP1) or methionine permease ( MUP1) enhanced the assimilation of glutamine or
      methionine in the ssy1Delta strain but could not fully suppress the derepression
      of the NCR-sensitive genes or MET genes. This result suggests that Ssy1p
      regulates not only the transcription of amino acid permease genes, but also
      transcription of many other nitrogen-metabolizing genes.

PMID- 12073088
TI  - Characterization of Candida albicans ASH1 in Saccharomyces cerevisiae.
AB  - Several fungi can undergo a dimorphic switch from yeast-like to hyphal or
      pseudohyphal forms in response to environmental cues. The Saccharomyces cerevisae
      GATA-type transcription factor Ash1p is required for diploid pseudohyphal
      differentiation during nitrogen starvation. In haploid cells, Ash1p is essential
      for the cell-type specific repression of the HO gene. We cloned CaAsh1, a
      putative homologue of Ash1p from the pathogen Candida albicans. Although the
      overall similarity of CaAsh1p and Ash1p is modest, both proteins show significant
      homology in their carboxy termini. Upon expression in budding yeast, CaASH1 mRNA
      is asymmetrically sorted during cell division, which is similar to the fate of
      ASH1 mRNA. Cell-specific CaASH1 mRNA localization results in an asymmetric CaAsh1
      protein distribution and an accumulation of the protein in daughter cell nuclei.
      CaAsh1 is unable to repress HO expression in S. cerevisiae but can replace ScAsh1
      function during pseudohyphal growth. This suggests a partial functional
      similarity of the two Ash1 proteins.

PMID- 12073089
TI  - Characterization of Cu, Zn-superoxide dismutase-deficient mutant of fission yeast
      Schizosaccharomyces pombe.
AB  - A Cu, Zn-superoxide dismutase gene ( sod1+) deletion mutant of fission yeast
      Schizosaccharomyces pombe was constructed and its properties were investigated.
      Superoxide dismutase activity was not detected in the mutant on activity staining
      of polyacrylamide gels. The mutant showed cysteine or methionine and lysine
      auxotrophy, slow growth and sensitivity to menadione. While expression of the
      apt1+ gene, induction of which depends on the Pap1 transcription factor, was
      induced at the same concentration of menadione in both the wild-type cell and the
      sod1 mutant, expression of the gpx1+ gene, induction of which depends on the Atf1
      transcription factor, was induced at a lower concentration of menadione in the
      mutant compared with the wild-type control. Expression of the sod1+ gene was
      induced by oxidative stress and no induction was observed in pap1, prr1 and spc1
      mutants.

PMID- 12073090
TI  - Cloning and relational analysis of 15 novel fungal endoglucanases from family 12
      glycosyl hydrolase.
AB  - Cellulases belong to the large family of glycosyl hydrolases (GHs) and are
      produced by a variety of bacteria and fungi. These extracellular enzymes act as
      endoglucanases (EGs), cellobiohydrolases or beta-glucosidases. In this paper, we
      describe molecular screening for EGs from the GH family 12. Using three
      homologous sequence boxes deduced from five previously known members of the
      family, we analysed 22 cellulase-producing fungal strains obtained from a diverse
      area of the fungal kingdom. Polymerase chain reactions using degenerate primers
      designed to the homologous protein boxes were used to identify the family 12
      homologues. Several fungi showed the presence of multiple versions of the gene,
      while amino acid sequence analysis showed diversity in 15 novel members of the
      family, ranging from 26% to 96% similarity. Our sequence analysis shows that the
      phylogenetic tree of family 12 EGs can be divided into four subfamilies: 12-1
      (fungal group I), 12-2 (fungal group II), 12-3 ( Streptomyces group in which
      Rhodothermus marinus fits) and 12-4 ( Thermophiles group). Erwinia carotovora may
      form a new subgroup.

PMID- 12073091
TI  - Nht2, a copia LTR retrotransposon from a conditionally dispensable chromosome in
      Nectria haematococca.
AB  - In the plant pathogenic ascomycete Nectria haematococca mating population (MP)
      VI, the conditionally dispensable chromosomes are unstable during sexual
      reproduction. During mapping of such a chromosome, three dispersed repeats were
      identified. Nht2, one of these repeated elements, is a long terminal repeat (LTR)
      retrotransposon that is 5.9 kb in length. Its deduced amino acid sequence is
      homologous to the four enzymatic domains characteristic of copia
      retrotransposons, but it contains multiple stop codons and probably is no longer
      able to transpose autonomously. Nht2's LTRs differ at ten positions and the
      characteristics of these differences resemble the changes induced by repeat
      induced point mutation (RIP) in Neurospora crassa. The likelihood that Nectria
      haematococca MP VI has a RIP-like process, however, is reduced by the fact that a
      multi-copy transposon cloned from the same ascospore isolate as Nht2 encodes an
      intact open reading frame. Nht2 is broadly distributed among isolates collected
      from a variety of host plants. A limited survey of three field isolates suggests
      that Nht2 is on only one or a few chromosomes in every genome. Nht2's degeneracy
      and its widespread distribution within the species both suggest that it is an
      ancient element within N. haematococca MP VI.

PMID- 12073092
TI  - Distribution of the pea pathogenicity ( PEP) genes in the fungus Nectria
      haematococca mating population VI.
AB  - Previous studies identified a cluster of six genes that are expressed in the
      fungus Nectria haematococca mating population VI during infection of pea. Four of
      these genes were shown to contribute to pathogenicity on pea and were called PEP
      genes for pea pathogenicity. The cluster is located on a "conditionally
      dispensable" (CD) chromosome and has features similar to bacterial pathogenicity
      islands. In this study, the occurrence and location of members of the PEP cluster
      were analyzed in laboratory strains and nine pea pathogenic and 16 non-pea
      pathogenic field isolates of N. haematococca. Our results indicate that all pea
      pathogenic isolates have homologues for all six genes present in the PEP cluster
      and the homologues appear to be clustered. PEP homologues are also present in
      isolates that are not pathogenic on pea, although none of these isolates have
      homologues of all six genes. In addition, PEP homologues are found in CD
      chromosomes and in other chromosomes. Isolates without PEP homologues are
      virulent on ripe tomato fruits and carrot roots, indicating that PEP genes are
      not required for pathogenicity on these hosts.

PMID- 12073094
TI  - Looking beyond the details: a rise in system-oriented approaches in genetics and
      molecular biology.
AB  - With the ever-increasing flow of high-throughput gene expression, protein
      interaction and genome sequence data, researchers gradually approach a system
      level understanding of cells and even multi-cellular organisms. Systems biology
      is an emerging field that enables us to achieve in-depth understanding at the
      system level. For this, we need to establish methodologies and techniques that
      enable us to understand biological systems as systems, which means to understand:
      (1) the structure of the system, such as gene/metabolic/signal transduction
      networks and physical structures, (2) the dynamics of such systems, (3) methods
      to control systems, and (4) methods to design and modify systems to generate
      desired properties. However, the meaning of "system-level understanding" is still
      ambiguous. This paper reviews the current status of the field and outlines future
      research directions and issues that need to be addressed.

PMID- 12073093
TI  - Genealogical relationships among laboratory strains of Chlamydomonas reinhardtii
      as inferred from matrix metalloprotease genes.
AB  - Almost all research on Chlamydomonas reinhardtii has utilized wild-type strains
      of three principal stock lines (Sager, Cambridge, Ebersold-Levine), which
      traditionally has been assumed to be descendants of a single zygote isolated by
      Smith. We previously noticed that there are several sequence differences in a
      single-copy gene of gametolysin, mmp1, between the mt+ and mt- strains employed.
      To further examine the polymorphisms among the three lines, we obtained 18
      representative strains of all three descendant lines of Smith's isolate, nine
      strains recently isolated from the wild and one strain (CC-1373 mt+) of C.
      smithii, a strain from Smith's collection interfertile with these C. reinhardtii
      strains; and we compared the mmp1-3'UTR by RFLP and sequencing analyses. Sequence
      divergences were found between the mt+ and mt- strains of both the Sager and
      Cambridge lines, but not between the two mating-type strains of the Ebersold
      Levine line. We also examined the polymorphisms, using the 3'UTRs of two other
      mmp genes and the introns of ypt4 and fus1. Based on the results, we conclude
      that it is genetically impossible for all the current C. reinhardtii lines to be
      the immediate descendants of a single zygote.

PMID- 12073095
TI  - PDR2 Gain-of-function mutations eliminate the need for Pdr1 and require the UBP6
      product for resistance to translational inhibitors.
AB  - The yeast YRR1 gene was identified as a sequence encoding a protein that is
      related in structure to the Pdr1 and Pdr3 zinc cluster transcription factors.
      Dominant gain-of-function mutations were recovered that cause a multidrug
      resistance to inhibitors transported by the SNQ2 and YOR1 proteins. It was
      previously reported by others that null mutations in YRR1 cause hypersensitivity
      to these agents. In this study, evidence is presented for allelism between YRR1
      and a previously identified locus: PDR2. Further characterization of
      hyperresistant PDR2 alleles and the initial characterization of a loss-of
      function mutation created by a Tn3 insertion are described. Surprisingly, the
      PDR2-2-mediated hyperresistance to chloramphenicol, anisomycin, and cycloheximide
      requires the function of the UBP6 gene and at least one other gene product. The
      PDR2-2 allele eliminates the requirement for Pdr1 although, in our genetic
      backgrounds, elimination of Pdr2 function has little or no phenotypic effect.

PMID- 12073096
TI  - Isolation of genes coding for Ade2 and Ura3 homologues from the multinuclear
      yeast Dipodascus magnusii.
AB  - Dipodascus magnusii is a nonconventional yeast species with giant multinuclear
      cells. We constructed two genomic DNA libraries in plasmid vectors and isolated
      the first two D. magnusii protein-encoding genes, DmADE2 and DmURA3, coding for
      phosphoribosylaminoimidazole carboxylase and orotidine-5'-phosphate
      decarboxylase, respectively. Both genes represent functional orthologues, since
      they complement ade2 and ura3 mutations in Saccharomyces cerevisiae and their
      putative products possess conserved sequences important for enzymatic activities.
      Moreover, the results of Southern blot analysis indicate that the genome of D.
      magnusii contains additional, paralogous sequences of the DmADE2 and DmURA3
      genes.

PMID- 12073098
TI  - Molecular characterization of the Pri3 gene encoding a cysteine-rich protein,
      specifically expressed during fruiting initiation within the Agrocybe aegerita
      complex.
AB  - Coding and regulating sequences of Pri3 (a novel gene specifically expressed in
      both nucleus types of dikaryons during fruiting initiation) were compared within
      nine strains of the Agrocybe aegerita complex originating from Europe, Asia and
      Latin America. Highly homologous coding sequences were found; and the 95-amino
      acid-long PRI3 deduced proteins all shared eight cysteines and eight glycines, a
      putative signal peptide suggesting an extra-cellular localization, a protein
      kinase C site (T(70)) and a cAMP-dependent kinase site (S(74)). The PRI3 proteins
      presented no significant homologies with already known proteins and constitute a
      new class of small cysteine-rich proteins. Within the 5' uncoding regions, two
      leader introns and a putative upstream regulating sequence resembling the QA1-F
      activator site were highly conserved. Comparison of the gene sequences within the
      A. aegerita complex suggested a divergent evolution of the European and
      Asian/Latin American groups of genes.

PMID- 12073097
TI  - Transgenic assessment of CFP-mediated cercosporin export and resistance in a
      cercosporin-sensitive fungus.
AB  - Cercosporin is a toxic polyketide produced by many phytopathogenic members of the
      fungal genus Cercospora. Cercospora species, themselves, exhibit the highest
      level of self-resistance to this almost universally toxic photosensitizer.
      Although the mechanism of cercosporin self-resistance is multi-faceted, partial
      resistance does appear to be provided by the encoded product of CFP ( cercosporin
      facilitator protein), a gene recently isolated from the pathogen of soybean, C.
      kikuchii. CFP has significant similarity to the major facilitator superfamily of
      integral membrane transport proteins. We expressed CFP in the cercosporin non
      producing, cercosporin-sensitive fungus, Cochliobolus heterostrophus, in order to
      assess the transport activity of CFP and the contribution of CFP to cercosporin
      resistance in a fungal species free of endogenous toxin production. Expression of
      the CFP transgene in this fungus results in increased resistance to cercosporin
      due, apparently, to its export out of the fungus.

PMID- 12073100
TI  - Temperature sensitivity of RNA editing and intron splicing reactions in the
      plastid ndhB transcript.
AB  - Primary transcripts in higher plant cell organelles undergo a series of essential
      RNA processing steps, including 5'- and 3'-terminal maturation, intron splicing
      and RNA editing. Most of the protein factors involved in these RNA processing
      mechanisms are still unknown. Also, little is known about the environmental and
      developmental factors regulating RNA processing events in plastids. Here we have
      tested the influence of the environmental factor temperature on RNA processing in
      the ndhB mRNA from tobacco plastids. We find that, whereas temperature increase
      to 37 degrees C fully inhibits RNA editing at only one out of nine sites in the
      tobacco ndhB transcript, further temperature increase to 42 degrees C selectively
      blocks editing at two additional sites. As these temperature effects are strictly
      site-specific, our findings provide evidence for the existence of site-specific
      editing factors which exhibit differential temperature sensitivity. Furthermore,
      splicing of the group II intron present in the ndhB pre-mRNA is largely blocked
      at 42 degrees C, suggesting that chloroplast RNA processing steps are more
      sensitive to high temperature than chloroplast transcription. Our findings may
      also suggest that impaired plastid RNA processing contributes to the loss of
      chloroplast function upon plant growth at high temperature.

PMID- 12073099
TI  - Mitochondrial DNA polymorphisms in the human pathogenic fungus Cryptococcus
      neoformans.
AB  - This study examined mitochondrial DNA (mtDNA) restriction site polymorphisms
      among 416 strains of the human pathogenic yeast Cryptococcus neoformans from the
      United States and Japan. The strains included 378 serotype A, 14 serotype D, 18
      serotype AD, two serotype B, and two strains whose serotype could not be
      determined using current commercial monoclonal antibodies. Portions of two genes
      were examined: (1) the mitochondrial large ribosomal RNA gene (mtLrRNA) and (2)
      the NADH dehydrogenase subunit 2 ( ND2). To screen for polymorphisms among the
      416 strains, the endonuclease MaeIII was used to digest the PCR-amplified mtLrRNA
      gene fragment and three endonucleases ( BanI, AluI, MseI) were used to digest the
      PCR-amplified ND2 gene fragment. Four mtDNA haplotypes were identified among
      these strains. All strains of serotype A had mtDNA haplotype I, strains of
      serotype D had haplotype II, and strains of serotype B had haplotypes III and IV.
      Of the two non-typable strains, one was haplotype I while the other was haplotype
      II. Among the strains of serotype AD, 14 were haplotype I and the other four were
      haplotype II. These results were discussed in the context of recent findings
      regarding the origins of serotype AD strains and the observed uniparental mtDNA
      inheritance in laboratory crosses between strains of serotypes A and D.

PMID- 12073102
TI  - Articular cartilage repair: the role of bone morphogenetic proteins.

PMID- 12073101
TI  - Proteins are shared among RNA-protein complexes that form in the 5' untranslated
      regions of spinach chloroplast mRNAs.
AB  - Gene expression in chloroplasts is strongly regulated at the post-transcriptional
      level. Most post-transcriptional mechanisms require RNA-protein complexes. Here
      we report an analysis of RNA-protein complexes that form in the 5' untranslated
      regions (5'UTRs) of spinach chloroplast mRNAs. Previous studies from our
      laboratory showed that four ATP synthase 5'UTRs were able to compete with each
      other for binding by proteins in a chloroplast extract. This implied that at
      least some of the binding proteins recognized all four of those ATP synthase
      5'UTRs. Here, we examine whether the binding proteins are ATP synthase-specific
      by performing competition-binding assays between an ATP synthase 5'UTR and 5'UTRs
      from other chloroplast genes. Competition substrates were chosen to represent a
      wide range of chloroplast mRNAs, including those encoding the photosystems, NADH
      dehydrogenase, cytochromes and ribosomal subunits, and two previously unexamined
      ATP synthase subunits. Results from these experiments revealed that, although the
      ATP synthase-binding proteins do not bind universally to every chloroplast 5'UTR,
      they do bind to the majority (12/14) of those examined. Thus, these RNA-binding
      proteins are candidates for factors that link the post-transcriptional expression
      of many chloroplast genes of disparate function.

PMID- 12073103
TI  - Ultrastructural changes in the transitional zone between articular cartilage and
      synovial membrane during the development of experimental osteoarthrosis.
AB  - We studied the ultrastructural changes that take place in the transitional zone
      between the articular cartilage and the synovial membrane during the development
      of experimental osteoarthrosis. We focused special attention on changes involving
      the proteoglycan complexes within the matrix of articular cartilage. We observed
      that changes in the transitional zone resemble those seen in articular cartilage
      during the development of osteoarthrosis. We also found transient cellular forms
      with fibroblast phenotype regulating the demands of both cartilage and synovial
      matrix. The transient nature of these elements determines the pronounced lability
      of this zone, and this may be related to the early development of osteoarthrosis.

PMID- 12073104
TI  - Effect of axial load on the cervical spine: a study of Congolese woodbearers.
AB  - We studied the cervical spine radiographically of 72 women between 24 and 78
      years of age who had carried wood on their head for a mean of 12 (5-41) years and
      compared the findings with those of 44 women between 21 and 80 years of age who
      served as controls. The height of the intervertebral discs and the vertebral
      bodies was statistically lower among woodbearers. Osteophytes were seen
      infrequently in pre-menopausal women in the study group, and their presence
      related to age ( P<0.01), short stature ( P<0.01), and the number of years
      working as a woodbearer ( P<0.05). The medullary canal was narrow in almost half
      of the post-menopausal woodbearers and narrower in those with degenerative
      changes ( P<0.01). Listhesis also was more frequent among woodbearers.

PMID- 12073106
TI  - Surgical treatment of displaced fractures of the glenoid cavity.
AB  - Between 1994 and 1999 ten patients with displaced glenoid cavity fractures were
      treated operatively. Nine of the fractures were the result of road traffic
      accidents. There were eight men and two women patients, their average age was 38
      (range 22-54) years, and the follow-up ranged from 18 to 84 months. Functional
      outcome was assessed in terms of pain, range of movement, muscle power, and
      performance of daily activities, and the results were excellent or good in eight
      patients.

PMID- 12073105
TI  - The treatment of double disruption of the superior shoulder suspensory complex.
AB  - Between January 1997 and March 2000, we treated 13 patients with double
      disruption of the superior shoulder suspensory complex (SSSC). The mean age of
      the patients was 42 (20-63) years. All patients had associated chest injuries,
      but there were no injuries of the brachial plexus or the peripheral nerves. Three
      patients, whose general condition was poor, were treated conservatively. Five
      underwent internal fixation of both the clavicular and scapular fractures and
      five of the clavicle only. We evaluated the clinical results using the Rowe Score
      after a minimum follow-up of 1 year. All fractures united. The average time to
      union was 14 weeks for clavicular and 11 for scapular fractures. There was
      malunion in four of five scapular fractures treated conservatively. A
      functionally better result was obtained in the surgical group with a mean Rowe
      Score of 88, compared with the conservative group whose mean score was 77.
      Surgical treatment for double disruption of the SSSC is a good option, allowing
      early rehabilitation and giving good functional results.

PMID- 12073107
TI  - Anterior knee laxity in young women varies with their menstrual cycle.
AB  - We studied 16 women 21-23 years old with regular menstrual cycles (28+/-4 days)
      and no history of knee injury. From their basal body temperatures and the serum
      concentrations of estradiol and progesterone, the follicular, ovulatory, and
      luteal phases were delineated. Using a KT-2000 arthrometer, anterior displacement
      at 89 N and 134 N and anterior terminal stiffness (N/mm) at 134 N were measured
      two or three times every week over a 4-week period. Eight men 21-23 years old
      were also measured. In women the anterior displacement at 89 N varied between the
      follicular and the ovulatory phase and between the follicular and the luteal
      phase ( P<0.05) and at 134 N between the follicular and the luteal phase (
      P<0.05). There were no statistical differences in the anterior displacement with
      time in men, nor in anterior terminal stiffness in either sex. We conclude that
      anterior cruciate ligament laxity in women might be dependent on the
      concentrations of hormones.

PMID- 12073108
TI  - Total hip replacement in sickle cell disease.
AB  - We report on 35 total hip replacement arthroplasties in 28 patients with
      avascular necrosis of the femoral head secondary to sickle cell disease (SCD).
      There were 15 men and 13 women with a mean age of 27.5 years. In all patients
      Harris hip scores improved from a mean of 36 pre-operative to 86 post-operative.
      However, at a mean follow-up of 9.5 (5-15) years six hips failed due to
      symptomatic aseptic loosening and one due to late deep infection. Our results
      support the decision to offer the procedure for patients with arthritic hips
      secondary to SCD. It is important that patients and surgeons should be aware of
      the wide varieties of complications.

PMID- 12073109
TI  - Impaction bone grafting for total hip revision.
AB  - We used impaction bone grafting for total hip revision on 26 hips in 25 patients.
      Average patient age was 68 (34-89) years, and average duration from last surgery
      was 9 years. In all cases morselized allograft bone was used for the graft, and
      the femoral component was a collarless, polished, tapered stem. Average duration
      of surgery was 2.4 h, intraoperative blood loss 600 cc, blood replacement 2.4
      units, and acute-care hospital stay 5 days. Complications were varus placement of
      the stem in two patients and postoperative development of varus in one, one
      intraoperative and three postoperative femoral fractures, and one postoperative
      dislocation. Average subsidence was 0.6 cm. We believe that most, if not all, of
      these complications could have been prevented.

PMID- 12073110
TI  - The effect of a lateral flare feature on implant stability.
AB  - We reviewed the X-rays of 109 patients with 115 primary total hip replacements
      utilizing a lateral flare cementless stem to assess axial migration and
      stability. The average follow-up was 48.6 (24-104) months. The average subsidence
      at 2 years was 0.32 mm, remaining at a level below 1 mm for the duration of the
      follow-up. Even though there were ten reoperations involving either the change of
      a polyethylene liner and the acetabular component, or both, none of the patients
      required a femoral stem revision. It was concluded that the proximal geometry of
      the stem provides significant initial stability, which seems to be preserved
      throughout a long follow-up period.

PMID- 12073112
TI  - Extracorporeally irradiated autografts in pelvic reconstruction after malignant
      tumour resection.
AB  - We treated 15 patients suffering from an extracompartmental malignant pelvic
      tumour by resecting the affected part of the bone, irradiating it
      extracorporeally with 300 Gy, and reimplanting it after having removed the bulk
      of the lesion. Adjuvant therapies were used according to the type and extension
      of the tumour. Follow-up was an average of 4 years 6 months. Complications were
      seen in 13 patients. Most mechanical complications were related to the use of hip
      arthroplasties. Internal fixation of the graft failed in one case only, infection
      was seen in three cases, and seven patients died after local recurrence.
      Functional scores were fair. Although many complications were seen, this method
      remains our treatment of choice.

PMID- 12073111
TI  - Modular megaprosthesis for proximal femoral tumors.
AB  - Fifteen patients with proximal femoral tumors had resection and limb salvage with
      an uncemented Kotz (HMRS) megaprosthesis. There were five osteosarcomas, four
      chondrosarcomas, one hemangioendothelioma, three fibrosarcomas, and two Ewing's
      sarcomas. The mean follow-up was 6.7 (range 3-10) years. Two patients died of
      causes not related to the prosthesis. The postoperative Musculoskeletal Tumor
      Society score (MSTS) score was 19 (range 12-26) for the remaining 13 patients.
      There were one aseptic loosening, two infections, and one local recurrence. The
      most frequent complication was hip dislocation at 20%. Reconstruction of proximal
      femoral tumors with a modular megaprosthesis is a good procedure, but hip
      instability remains a major problem.

PMID- 12073113
TI  - Infection after prosthetic reconstruction in limb salvage surgery.
AB  - Among 145 patients that underwent prosthetic reconstruction between 1985 and
      1998, infection developed in 18. Osteosarcoma was the most common primary tumour,
      and staphylococci were the major pathogenic organisms. Infections were controlled
      in five patients with debridement only and in two patients with a two-stage
      revision. Arthrodeses were performed in three and amputations in two. In six
      patients, infection was suppressed with antibiotics but not cured. Pulmonary
      metastasis developed in four of ten patients in whom chemotherapy was delayed or
      interrupted. Infection controls were poor in cases of delayed debridement over 2
      weeks, in cementless fixation of implant, and soft tissue defects ( P<0.01).
      Infection after prosthetic reconstruction is not only difficult to treat but also
      influences the prognosis reverse.

PMID- 12073114
TI  - The rate of instrument breakage during orthopaedic procedures.
AB  - The current study investigates instrument breakages during both emergency and
      elective orthopaedic surgery. Over a 2 year period a total of 7,775 procedures
      were performed. We found that 14 instruments were broken during 12 operative
      cases. Drill bits accounted for the largest proportion of breakages (11/14), and
      a specialist registrar was the lead surgeon in the majority (8/12) of cases. Only
      one case had a consultant as the lead surgeon. In seven cases the broken bit of
      the surgical instrument was left in the patient. Documentation of this peri
      operative complication was deficient, and the patient was often not informed.

PMID- 12073115
TI  - Bilateral hereditary micro-epiphyseal dysplasia: further delineation of the
      phenotype with 40 years follow-up.
AB  - Bilateral hereditary micro-epiphyseal dysplasia (BHMED) is a distinct skeletal
      dysplasia with specific clinical and radiological findings. It was first
      published in 1959. We have re-examined the original family for further
      delineation of the phenotype.

PMID- 12073116
TI  - Pathophysiology and imaging in inflammatory and blastomatous synovial diseases.
AB  - Variable pathologies are subsumed under the term "synovial disease", including
      common pathologies such as rheumatoid arthritis. While formerly radiologists had
      to rely on conventional radiographs and bone scintigraphy with their inherent
      problems in visualizing soft tissue, noninvasive imaging of the synovium has
      recently improved substantially with the technical development of MRI and
      (Doppler) ultrasound. These imaging modalities allow differentiation of
      characteristic pathologic features based on a profound knowledge of normal
      anatomy and pathophysiology.

PMID- 12073117
TI  - Magnetic resonance imaging of Osgood-Schlatter disease: the course of the
      disease.
AB  - OBJECTIVE: The purpose of this study was to clarify the nature of Osgood
      Schlatter disease (OSD) using MR images. DESIGN: Thirty boys (40 knees) with OSD
      diagnosed by clinical symptoms and signs were investigated with MRI. Longitudinal
      evaluation was undertaken in 22 patients and the mean follow-up was 1.5+/-0.9
      years. MR examinations were performed at least every 6 months in most cases. When
      a patient's symptoms changed, MRI was repeated and in cases where the initial MR
      examination showed an early or progressive stage of OSD, MRI was undertaken every
      month where possible. All MR examinations were performed in the sagittal plane
      with a 0.2 T imager. RESULTS: MR images were classified into five stages as
      follows: normal, early, progressive, terminal and healing. The stage of 11 knees
      (28%) did not change during the course of the study and 21 knees (53%) showed a
      change of at least one stage. Eight knees (20%) did not have follow-up MR
      studies. The initial MR examination was normal in nine knees. Eight knees were at
      the early stage at presentation. MR images showed edema-like changes around the
      tibial tuberosity. Ten knees were classified as in the progressive stage at the
      initial presentation and six knees were classified in this group during
      progression on follow-up MRI. MR images showed partial avulsion of the secondary
      ossification center, which was seen to be being pulled proximally. Eleven knees
      were at the terminal stage on presentation, where the avulsed parts of the
      secondary ossification center had become completely separated. Two knees were
      classified as in the healing stage at presentation and 19 knees progressed to the
      healing stage from the normal, early and progressive stages. The MR images showed
      the separated part that did not create the ossicle had recovered by osseous
      healing. On the other hand, radiographs of the early stage appeared almost
      normal, and in the progressive stage could not show the avulsed parts.
      CONCLUSIONS: We clarified the progress of OSD with MRI. The process of OSD
      started from the apophyseal stage and a tear appeared in the secondary
      ossification center, widening to an opened shell-like shape. This damage
      progressed to an ossicle in some cases. In short, the ossicle was formed from an
      avulsed portion. It was very difficult to show the course of OSD with
      radiography. MR images were especially useful for revealing early and progressive
      lesions of OSD.

PMID- 12073119
TI  - Accuracy of CT-guided biopsies in 359 patients with musculoskeletal lesions.
AB  - The study was undertaken to assess the diagnostic accuracy and clinical
      usefulness of computed tomography (CT)-guided biopsies and fine needle aspirates
      of musculoskeletal lesions. The analysis compared the accuracy according to
      anatomical location, size, type of lesion, and histology. On the basis of the
      information obtained by reviewing the report of the CT biopsy and comparing it
      with the final diagnosis for 359 cases, the overall accuracy was determined to be
      71%. The accuracy for 101 fine needle aspirations was 63% and for 258 CT-guided
      core biopsies was 74%. It is of note that the biopsies of 81 pelvic lesions had
      higher rates of diagnostic accuracy (81%) than those of 278 non-pelvic sites
      (68%), and especially 94 lesions of the spine (61%). The lowest success rates
      occurred in 26 patients with infectious diseases (50%). We conclude that these
      procedures remain the logical and safe choice for diagnostic studies of patients
      with lesions of the musculoskeletal system.

PMID- 12073118
TI  - Short tau inversion recovery and three-point Dixon water-fat separation sequences
      in acute traumatic bone fractures at open 0.35 tesla MRI.
AB  - OBJECTIVE: Fat suppression can be used to improve the diagnostic confidence in
      traumatic bone fractures of the extremities. We compared a three-point Dixon
      "sandwich" water-fat separation (WFS) sequence, resulting in a water-only and a
      fat-only image set after one excitation, with the STIR sequence on an open 0.35 T
      superconductive MR system. DESIGN AND PATIENTS: T1-weighted, STIR (2000/40
      [TR/TE]), and WFS (2000/36 [TR/TE]) MR images were prospectively obtained in 27
      patients with 40 radiologically diagnosed fractures immediately after first-line
      treatment. Signal-to-noise (S/N) ratio, contrast-to-noise (C/N) ratio, and bone
      marrow edema volumes were measured together with qualitative parameters (four
      point scale). RESULTS: WFS was significantly superior to STIR in all quantitative
      parameters (better S/N ratio, P<0.001; better C/N ratio, P<0.001; larger marrow
      edema, P <0.023; Wilcoxon signed rank test). Visibility of bone marrow edema,
      visibility of fracture line, and preservation of anatomical details were better
      with the WFS sequence ( P<0.001, P<0.001, P<0.001, respectively; ANOVA). Fat
      saturation was rated more homogeneous, however, with the STIR sequence (not
      significant; P<0.101). CONCLUSION: On the basis of qualitative and quantitative
      assessments, the three-point Dixon "sandwich" water-fat separation sequence was
      consistently superior to the STIR sequence in the delineation of traumatic
      fractures.

PMID- 12073120
TI  - True bursal pigmented villonodular synovitis.
AB  - We describe two cases of pigmented villonodular synovitis affecting true bursae.
      This study was also designed to discuss the term "pigmented villonodular
      bursitis", not confined to true synovial bursae, sometimes creating
      misunderstanding.

PMID- 12073121
TI  - Calcific tendinitis of the gluteus medius tendon with bone marrow edema mimicking
      metastatic disease.
AB  - A case of calcific tendinitis of the gluteus medius is presented. This report
      describes a patient with a history of breast cancer who had the combination of
      amorphous calcifications in the gluteus medius tendon and the MR finding of
      conspicuous bone marrow edema in the adjacent greater trochanter, prompting
      concern for metastatic disease. We present images from radiography, bone
      scanning, CT, and MR imaging. The unusual combination of findings in these
      studies should be considered conclusive for calcific tendinitis, and should not
      be confused with malignancy.

PMID- 12073122
TI  - MRI features of confirmed "pre-slip" capital femoral epiphysis: a report of two
      cases.
AB  - We describe the morphologic and signal changes detected about the proximal
      femoral growth plate in two patients with hip pain preceding the progression to
      slipped capital femoral epiphysis using magnetic resonance imaging.

PMID- 12073123
TI  - Avascular necrosis of the epiphysis of the first metatarsal bone.
AB  - We report a case of avascular necrosis of the epiphysis of the right first
      metatarsal in a 6-year-old boy. Radiographs showed sclerosis, collapse and a
      crescent sign in the epiphysis. The diagnosis was confirmed by magnetic resonance
      imaging and scintigraphy. Arch support was the therapy of choice. Six months
      after the onset of symptoms, a definite reossification was present. To our
      knowledge, this is the first radiological report of avascular necrosis of the
      epiphysis of the first metatarsal bone in the world literature, which prompted a
      review of the osteochondroses and their etiology.

PMID- 12073124
TI  - Clear cell chondrosarcoma mimicking chondroblastoma in a skeletally immature
      patient.
AB  - We report the case of a clear cell chondrosarcoma (CCCS) occurring in the femoral
      head of a 14-year-old skeletally immature boy. Radiographic examination revealed
      a well-defined, osteolytic lesion in the epiphysis of the femoral head. Given the
      patient's age and the radiographic appearance of the lesion, chondroblastoma was
      high on the differential diagnosis. A frozen section was performed at the time of
      open biopsy was felt to be consistent with either chondroblastoma or CCCS. CCCS
      in a skeletally immature patient was felt to be unlikely, so curettage and bone
      grafting was performed. Final pathology review, however, confirmed the diagnosis
      of CCCS. The patient was taken back to surgery 4 weeks later for a wide resection
      and hemiarthroplasty.

PMID- 12073125
TI  - Biotechnological production of 2-phenylethanol.
AB  - 2-Phenylethanol (2-PE) is an important flavour and fragrance compound with a rose
      like odour. Most of the world's annual production of several thousand tons is
      synthesised by chemical means but, due to increasing demand for natural flavours,
      alternative production methods are being sought. Harnessing the Ehrlich pathway
      of yeasts by bioconversion of L-phenylalanine to 2-PE could be an option, but in
      situ product removal is necessary due to product inhibition. This review
      describes the microbial production of 2-PE, and also summarizes the chemical
      syntheses and the market situation.

PMID- 12073127
TI  - Bacterial alkaline proteases: molecular approaches and industrial applications.
AB  - Proteolytic enzymes are ubiquitous in occurrence, being found in all living
      organisms, and are essential for cell growth and differentiation. The
      extracellular proteases are of commercial value and find multiple applications in
      various industrial sectors. Although there are many microbial sources available
      for producing proteases, only a few are recognized as commercial producers. A
      good number of bacterial alkaline proteases are commercially available, such as
      subtilisin Carlsberg, subtilisin BPN' and Savinase, with their major application
      as detergent enzymes. However, mutations have led to newer protease preparations
      with improved catalytic efficiency and better stability towards temperature,
      oxidizing agents and changing wash conditions. Many newer preparations, such as
      Durazym, Maxapem and Purafect, have been produced, using techniques of site
      directed mutagenesis and/or random mutagenesis. Directed evolution has also paved
      the way to a great variety of subtilisin variants with better specificities and
      stability. Molecular imprinting through conditional lyophilization is coming up
      to match molecular approaches in protein engineering. There are many
      possibilities for modifying biocatalysts through molecular approaches. However,
      the search for microbial sources of novel alkaline proteases in natural diversity
      through the "metagenome" approach is targeting a hitherto undiscovered wealth of
      molecular diversity. This fascinating development will allow the biotechnological
      exploitation of uncultured microorganisms, which by far outnumber the species
      accessible by cultivation, regardless of the habitat. In this review, we discuss
      the types and sources of proteases, protease yield-improvement methods, the use
      of new methods for developing novel proteases and applications of alkaline
      proteases in industrial sectors, with an overview on the use of alkaline
      proteases in the detergent industry.

PMID- 12073126
TI  - Biochemistry and molecular genetics of poly-gamma-glutamate synthesis.
AB  - Current research into poly-gamma-glutamate (PGA) and its biosynthesis is
      reviewed. In PGA-producing Bacillus subtilis, glutamate racemase supplies
      abundant DL-glutamate, the substrate for PGA synthesis. The pgsBCA genes of PGA
      producing B. subtilis, which encode the membrane-associated PGA synthetase
      complex PgsBCA, were characterized and the enzyme complex was suggested to be an
      atypical amide ligase based on its structure and function. A novel reaction
      mechanism of PGA synthesis is proposed.

PMID- 12073128
TI  - Heterotrophic bacteria growing in association with Methylococcus capsulatus
      (Bath) in a single cell protein production process.
AB  - The methanotrophic bacterium Methylococcus capsulatus (Bath) grows on pure
      methane. However, in a single cell protein production process using natural gas
      as methane source, a bacterial consortium is necessary to support growth over
      longer periods in continuous cultures. In different bioreactors of Norferm
      Danmark A/S, three bacteria consistently invaded M. capsulatus cultures growing
      under semi-sterile conditions in continuous culture. These bacteria have now been
      identified as a not yet described member of the Aneurinibacillus group, a
      Brevibacillus agri strain, and an acetate-oxidiser of the genus Ralstonia. The
      physiological roles of these bacteria in the bioreactor culture growing on
      natural, non-pure methane gas are discussed. The heterotrophic bacteria do not
      have the genetic capability to produce either the haemolytic enterotoxin complex
      HBL or non-haemolytic enterotoxin.

PMID- 12073129
TI  - The use of co-immobilization of Trichosporon cutaneum and Bacillus licheniformis
      for a BOD sensor.
AB  - The microorganisms Trichosporon cutaneum and Bacillus licheniformis were used to
      develop a microbial biochemical oxygen demand (BOD) sensor. It was found that T.
      cutaneum gave a greater response to glucose, whereas B. licheniformis gave a
      better response to glutamic acid. Hence, co-immobilized T. cutaneum and B.
      licheniformis were used to construct a glucose and glutamic acid sensor with
      improved sensitivity and dynamic range. A membrane loading of T. cutaneum at
      1.1x10(8 )cells ml(-1) cm(-2) and B. licheniformis at 2.2x10(8) cells ml(-1) cm(
      2) gave the optimum result: a linear range up to 40 mg BOD l(-1) with a
      sensitivity of 5.84 nA mg(-1) BOD l. The optimized BOD sensor showed operation
      stability for 58 intermittent batch measurements, with a standard deviation of
      0.0362 and a variance of 0.131 nA. The response time of the co-immobilized
      microbial BOD sensor was within 5-10 min by steady-state measurement and the
      detection limit was 0.5 mg BOD l(-1). The BOD sensor was insensitive to pH in the
      range of pH 6.8-7.2.

PMID- 12073130
TI  - Large scale production and downstream processing of a recombinant porcine
      parvovirus vaccine.
AB  - Porcine parvovirus (PPV) virus-like particles (VLPs) constitute a potential
      vaccine for prevention of parvovirus-induced reproductive failure in gilts. Here
      we report the development of a large scale (25 l) production process for PPV-VLPs
      with baculovirus-infected insect cells. A low multiplicity of infection (MOI)
      strategy was efficiently applied avoiding the use of an extra baculovirus
      expansion step. The optimal harvest time was defined at 120 h post-infection at
      the MOI used, with the cell concentration at infection being 1.5x10(6) cells/ml.
      An efficient purification scheme using centrifugation, precipitation and
      ultrafiltration/diafiltration as stepwise unit operations was developed. The
      global yield of the downstream process was 68%. Baculovirus inactivation with
      Triton X-100 was successfully integrated into the purification scheme without an
      increase in the number of process stages. Immunogenicity of the PPV-VLPs tested
      in guinea pigs was similar to highly purified reference material produced from
      cells cultured in the presence of serum-containing medium. These results indicate
      the feasibility of industrial scale production of PPV-VLPs in the baculovirus
      system, safety of the product, and the potency of the product for vaccine
      application.

PMID- 12073131
TI  - Elicitor-like effects of low-energy ultrasound on plant (Panax ginseng) cells:
      induction of plant defense responses and secondary metabolite production.
AB  - In this work we examined the elicitor-like effects of low-energy ultrasound (US)
      on plant cells with respect to the induction of plant defense responses and
      secondary metabolite production. Panax ginseng cells in suspension culture were
      exposed to US (power <or=0.1 W/cm(3) at 38.5 kHz fixed frequency) for short
      periods of time (30 s-6 min). Two early events in plant defense metabolism and
      signal transduction pathways, the increased cross-membrane ion fluxes (Ca(2+)
      influx and K(+) efflux/H(+) influx) and the production of active oxygen species
      (AOS), were detected in sonicated cultures within 2 min after US exposure. These
      responses could be induced with small doses of US energy, 0.6-0.8 J/cm(3), and
      enhanced by increasing US energy within a non-inhibitory range. US treatment
      stimulated the synthesis of useful secondary metabolites, saponins of ginseng
      cells, without causing any net loss of the biomass yield of ginseng cell
      cultures. These results suggest that US can act as a potent abiotic elicitor to
      induce the defense responses of plant cells and to stimulate secondary metabolite
      production in plant cell cultures.

PMID- 12073132
TI  - Impact of electrode composition on electricity generation in a single-compartment
      fuel cell using Shewanella putrefaciens.
AB  - The production of electricity by Shewanella putrefaciens in the absence of
      exogenous electron acceptors was examined in a single compartment fuel cell with
      different types of electrodes and varying physiological conditions. Electricity
      production was dependent on anode composition, electron donor type and cell
      concentration. A maximum current of 2.5 mA and a current density of 10.2
      mW/m(2)electrode was obtained with a Mn(4+) graphite anode, 200 mM sodium lactate
      and a cell concentration of 3.9 g cell protein/ml. Current production by S.
      putrefaciens was enhanced 10-fold when an electron mediator (i.e., Mn(4+) or
      neutral red) was incorporated into the graphite anode.

PMID- 12073133
TI  - Cometabolic ring fission of dibenzofuran by Gram-negative and Gram-positive
      biphenyl-utilizing bacteria.
AB  - Thirty-five strains of soil bacteria were grown with biphenyl (BP) and tested for
      their capacity to cooxidize dibenzofuran (DBF). During metabolism of DBF, the
      culture medium of 17 strains changed from colorless to orange, indicating a meta
      cleavage pathway of DBF degradation. The ring cleavage product of these isolates
      was shown to be 2-hydroxy-4-(3'-oxo-3' H-benzofuran-2'-yliden)but-2-enoic acid
      (HOBB). The strain SBUG 271, studied in detail and identified as Rhodococcus
      erythropolis, degraded DBF via 1,2-dihydroxydibenzofuran. The ensuing meta
      cleavage yielded HOBB and salicylic acid. In addition, the four monohydroxylated
      monomers of DBF and two metabolites, which were not further characterized, were
      detected. Thus, our results demonstrate that the metabolic mechanism involves
      lateral dioxygenation of DBF followed by meta-cleavage and occurs in Gram
      negative as well as in Gram-positive BP-degrading bacteria.

PMID- 12073134
TI  - Inhibition of bacterial alpha-glucosidases by castanospermine in pure cultures
      and activated sludge.
AB  - Castanospermine (CAST) is a known and potent inhibitor of various alpha
      glucosidases in eukaryotes. In this work, we elucidated whether CAST could also
      be used for determining bacterial alpha-glucosidase activity, when measured with
      4-methylumbelliferyl-alpha- D-glucoside as a substrate, both in a complex
      bacterial community, in activated sludge and in pure cultures of bacterial
      isolates. We found that 140 microM CAST inhibited alpha-glucosidase activity by
      30% in a pure culture of Pseudomonas stutzeri. The alpha-glucosidase activity in
      Chryseobacterium gleum was inhibited by 90% at a concentration of 150 microM
      CAST, whereas the alpha-glucosidase in Paracoccus denitrificans was resistant to
      the inhibitor. CAST (140 microM) reduced alpha-glucosidase activity in activated
      sludge by 40%, the respiration rate being reduced by only 12%. No significant
      inhibition of the respiration rate was observed in Ps. stutzeri or Pa.
      denitrificans, whereas the respiration rate in C. gleum grown in a medium
      containing starch was inhibited by 50% with 140 microM CAST. No effect of CAST
      was observed in C. gleum grown in a complex medium. This indicated that CAST, at
      the concentration used, did not cause a general negative effect on bacterial
      activity. The results suggest that the CAST assay may potentially be useful in
      determining whether alpha-glucosidase activity, starch, poly- and disaccharides
      contribute appreciably to the overall activity of a bacterial community. However,
      the assay should not be used for quantitative measurements of such activity.

PMID- 12073135
TI  - 2-Amino-3-carboxy-1,4-naphthoquinone affects the end-product profile of
      bifidobacteria through the mediated oxidation of NAD(P)H.
AB  - Glucose metabolism of bifidobacteria in the presence of 2-amino-3-carboxy-1,4
      naphthoquinone (ACNQ), a specific growth stimulator for bifidobacteria, and
      ferricyanide (Fe(CN)(6)(3-)) as an extracellular electron acceptor was examined
      using resting cells of Bifidobacterium longum and Bifidobacterium breve. NAD(P)H
      in the cells is oxidized by ACNQ with the aid of diaphorase activity, and reduced
      ACNQ donates the electron to Fe(CN)(6)(3-). Exogenous oxidation of NADH by the
      ACNQ/Fe(CN)(6)(3-) system suppresses the endogenous lactate dehydrogenase
      reaction competitively, which results in the remarkable generation of pyruvate
      and a decrease in lactate production. In addition, a decrease in acetate
      generation is also observed in the presence of ACNQ and Fe(CN)(6)(3-). This
      phenomenon could not be explained in terms of the fructose-6-phosphate
      phosphoketolase pathway, but suggests rather that glucose is partially
      metabolized via the hexose monophosphate pathway. This was verified by NADP(+)
      induced reduction of Fe(CN)(6)(3-) in cell-free extracts in the presence of ACNQ.
      Effects of the ACNQ/Fe(CN)(6)(3-) system on anaerobically harvested cells were
      also examined. Stoichiometric analysis of the metabolites from the pyruvate
      formate lyase pathway suggests that exogenous oxidation of NADH is an efficient
      method to produce ATP in this pathway.

PMID- 12073137
TI  - Simultaneous detection and removal of organomercurial compounds by using the
      genetic expression system of an organomercury lyase from the transposon Tn MERI1.
AB  - Using a newly identified organomercury lyase gene (merB3) expression system from
      Tn MERI1, the mercury resistance transposon first found in Gram-positive
      bacteria, a dual-purpose system to detect and remove organomercurial
      contamination was developed. A plasmid was constructed by fusing the promoterless
      luxAB genes as bioluminescence reporter genes downstream of the merB3 gene and
      its operator/promoter region. Another plasmid, encoding mer operon genes from
      merR1 to merA, was also constructed to generate an expression regulatory protein,
      MerR1, and a mercury reductase enzyme, MerA. These two plasmids were transformed
      into Escherichia coli cells to produce a biological system that can detect and
      remove environmental organomercury contamination. Organomercurial compounds, such
      as neurotoxic methylmercury at nanomolar levels, were detected using the
      biomonitoring system within a few minutes and were removed during the next few
      hours.

PMID- 12073136
TI  - Degradation of phenanthrene, methylphenanthrenes and dibenzothiophene by a
      Sphingomonas strain 2mpII.
AB  - Strain Sphingomonassp. (2MPII), isolated from marine sediment, was able to
      utilize phenanthrene (P) or 2-methylphenanthrene (2MP) as the sole carbon source.
      However, 9-methylphenanthrene (9MP) and dibenzothiophene (DBT) were weakly
      degraded. The degradation rates of 9MP and DBT increased in the presence of 2MP,
      whilst the degradation rate of 2MP increased in the presence of 9MP. However, the
      presence of DBT inhibited the degradation of 2MP. DBT sulfone, a DBT metabolite,
      was not assimilated by the bacteria and its presence also decreased the
      degradation rate of 2MP.

PMID- 12073138
TI  - Monitoring the denitrification of wastewater containing high concentrations of
      nitrate with methanol in a sulfur-packed reactor.
AB  - Biological denitrification of high nitrate-containing wastewater was examined in
      a sulfur-packed column using a smaller amount of methanol than required
      stoichiometrically for heterotrophic denitrification. In the absence of methanol,
      the observed nitrate removal efficiency was only about 40%, and remained at 400
      mg NO(3)(-)-N/l, which was due to an alkalinity deficiency of the pH buffer and
      of CO(2) as a carbon source. Complete denitrification was achieved by adding
      approximately 1.4 g methanol/g nitrate-nitrogen (NO(3)(-)-N) to a sulfur-packed
      reactor. As the methanol concentration increased, the overall nitrate removal
      efficiency increased. As influent methanol concentrations increased from 285 to
      570, 855, and 1,140 mg/l, the value of Delta mg alkalinity as CaCO(3)
      consumed/Delta mg NO(3)(-)-N removed increased from -1.94 to -0.84, 0.24, and
      0.96, and Delta mg SO(4)(2-) produced/Delta mg NO(3)(-)-N removed decreased from
      4.42 to 3.57, 2.58, and 1.26, respectively. These results imply the co-occurrence
      of simultaneous autotrophic and heterotrophic denitrification. Sulfur-utilizing
      autotrophic denitrification in the presence of a small amount of methanol is very
      effective at decreasing both sulfate production and alkalinity consumption. Most
      of methanol added was removed completely in the effluent. A small amount of
      nitrite accumulated in the mixotrophic column, which was less than 20 mg NO(2)(-)
      -N/l, while under heterotrophic denitrification conditions, nitrite accumulated
      steadily and increased to 60 mg NO(2)(-) -N/l with increasing column height.

PMID- 12073139
TI  - A biomarker for the identification of cattle fecal pollution in water using the
      LTIIa toxin gene from enterotoxigenic Escherichia coli.
AB  - This research describes a method based on PCR to identify cattle fecal pollution
      in water using a portion of the heat labile toxin IIA (LTIIa) gene from
      enterotoxigenic Escherichia coli (ETEC). We describe the development of the
      primers and target. DNA extracts (221) from different animal fecal and human
      sewage samples were screened and showed no cross-reactivity. Minimum detection
      limits using centrifugation and filtration methods to concentrate E. coli seeded
      into stream, ocean, and secondary effluent waters were found to be at femtogram
      and attogram levels, respectively. Stability of the biomarker in stream, ocean,
      and secondary effluent waters was 2-4 weeks for all water types. Finally, 33 farm
      lagoon and waste samples were collected and 31 tested to validate the method; 93%
      were positive for the LTIIa trait when >1,000 E. coli were screened and 100%
      positive when >10(5) E. coli were screened. Prevalence of the toxin gene in the
      E. coli population affected the outcome of the analyses. The cow biomarker can be
      used in watershed studies to identify cattle waste with great accuracy if the
      appropriate numbers of E. coli are screened.

PMID- 12073141
TI  - Aerobic degradation of 2,4,6-trichlorophenol by a microbial consortium -
      selection and characterization of microbial consortium.
AB  - A microbial consortium that efficiently degrades 2,4,6-TCP (2,4,6
      trichlorophenol), as the sole source of carbon and energy under aerobic
      conditions was selected from municipal activated sludge. Six bacterial strains,
      designated S(1), S(2), S(3), S(4), S(5) and S(6), were isolated from the selected
      consortium and five were identified as Sphingomonas paucimobilis (S(2), S(3)),
      Burkholderia cepacia(S(4)), Chryseomonas luteola (S(5)) and Vibrio metschnikovii
      (S(6)). After prolonged cultivation followed by successive transfers, the
      consortium's degradation ability was improved and reached a specific degradation
      rate of 34 mg 2,4,6-TCP g(-1) dry weight h(-1) (about 51 mg 2,4,6-TCP g(-1) cell
      protein h(-1)). The soluble chemical oxygen demand, chloride and oxygen uptake
      balance data clearly indicate the complete dechlorination and mineralization of
      2,4,6-TCP. The consortium's activity was not inhibited by 2,4,6-TCP
      concentrations <or=400 mg l(-1). The highest specific growth rate (micro(max) of
      0.01 h(-1)) was achieved at 2,4,6-TCP concentration <or=200 mg l(-1), and the
      inhibition constant ( K(i)) was 610 mg l(-1) according to the Haldane inhibition
      kinetic model. An inoculum size up to 120 mg l(-1) cell dry weight is desirable
      in order to avoid a lag phase and to allow faster degradation of 2,4,6-TCP.

PMID- 12073140
TI  - Assessment of effluent turbidity in mesophilic and thermophilic activated sludge
      reactors - origin of effluent colloidal material.
AB  - Two lab-scale plug flow activated sludge reactors were run in parallel for 4
      months at 30 and 55 degrees C. Research focussed on: (1) COD (chemical oxygen
      demand) removal, (2) effluent turbidity at both temperatures, (3) the origin of
      effluent colloidal material and (4) the possible role of protozoa on turbidity
      levels. Total COD removal percentages over the whole experimental period were
      66+/-7% at 30 degrees C and 53+/-11% at 55 degrees C. Differences in total COD
      removal between both systems were due to less removal of soluble and colloidal
      COD at 55 degrees C compared to the reference system. Thermophilic effluent
      turbidity was caused by a combination of influent colloidal particles that were
      not effectively retained in the sludge flocs, and erosion of the thermophilic
      activated sludge itself, as shown by denaturing gradient gel electrophoresis
      (DGGE) profiles. DGGE analysis of PCR-amplified 16S rDNA fragments from
      mesophilic and thermophilic sludge differed, indicating that different microbial
      communities were present in the two reactor systems. The effects of protozoal
      grazing on the effluent turbidity of both reactors was negligible and thus could
      not account for the large turbidity differences observed.

PMID- 12073142
TI  - Developing and sustaining 3-chlorophenol-degrading populations in up-flow
      anaerobic column reactors under circum-denitrifying conditions.
AB  - Microbial consortia capable of degrading 3-chlorophenol (3-CP) were enriched in
      continuous up-flow column reactors under circum-denitrifying conditions. 3-CP
      degradation capability was developed and sustained when 3-CP was supplied at 16
      21 microM, although suppression of the 3-CP degradation capability was observed
      when 3-CP was supplied at 42 microM. When 3-CP was stably degraded, the ratio of
      nitrate consumption to 3-CP degradation approached the theoretical stoichiometric
      value, which was calculated by assuming a 3-CP degradation-dependent nitrate
      reduction. Batch-incubation experiments demonstrated that the microbial
      consortium that was enriched in the column reactors required either nitrate or
      oxygen for degrading 3-CP, while 3-CP was not degraded under sulfate-degrading
      conditions. Although many attempts were made to sustain the microbial 3-CP
      degradation capability under denitrifying conditions, mostly in batch cultures,
      none of them have been successful so far. Therefore, the results obtained in this
      study may be the first to demonstrate sustainable 3-CP degradation capability
      under circum-denitrifying conditions.

PMID- 12073143
TI  - The human anti-thyroid peroxidase autoantibody repertoire in Graves' and
      Hashimoto's autoimmune thyroid diseases.
AB  - Human anti-thyroid peroxidase (TPO) autoantibodies (aAb) are generated during
      autoimmune thyroid diseases (AITD). Within recent years, increasing knowledge of
      the TPO-specific aAb repertoire, gained mainly by the use of combinatorial
      library methodology, has led to the cloning and sequencing of around 180 human
      anti-TPO aAb. Analysis of the immunoglobulin (Ig) variable (V) genes encoding the
      TPO aAb in the ImMunoGeneTics database (IMGT) (http://imgt.cines.fr) reveals
      major features of the TPO-directed aAb repertoire during AITD. Heavy chain VH
      domains of TPO-specific aAb from Graves' disease patients preferentially use D
      proximal IGHV1 genes, whereas those from Hashimoto's thyroiditis are
      characterized more frequently by IGHV3 genes, mainly located in the middle of the
      IGH locus. A large proportion of the anti-TPO heavy chain VH domains is obtained
      following a VDJ recombination process that uses inverted D genes. J distal IGKV1
      and IGLV1 genes are predominantly used in TPO aAb. In contrast to the numerous
      somatic hypermutations in the TPO-specific heavy chains, there is only limited
      amino acid replacement in most of the TPO-specific light chains, particularly in
      those encoded by J proximal IGLV or IGKV genes, suggesting that a defect in
      receptor editing can occur during aAb generation in AITD. Among the predominant
      IGHV1 or IGKV1 TPO aAb, conserved somatic mutations are the hallmark of the TPO
      aAb repertoire. The aim of this review is to provide new insights into aAb
      generation against TPO, a major autoantigen involved in AITD.

PMID- 12073144
TI  - A novel mutation in PTPRC interferes with splicing and alters the structure of
      the human CD45 molecule.
AB  - CD45, encoded by the protein tyrosine phosphatase receptor type C ( PTPRC) gene,
      is essentially involved in maturation, activation, and migration of immune cells.
      Lack of CD45 results in severe immunodeficiency, and alterations of the receptor
      may result in autoimmunity. Here, we describe a novel mutation in PTPRCas a cause
      of variant CD45 expression in humans. Several members of a multiple sclerosis
      multiplex family showed expression of CD45RA on memory T cells and monocytes. The
      variant expression pattern was linked to the PTPRCgene by DNA microsatellite
      studies. DNA analysis identified a novel point mutation in exon 4 (position 59 C-
      >A) in all family members with variant CD45 expression, but not in donors with
      normal CD45 expression. The mutation interferes with alternative splicing and
      alters amino acid sequence (H-->Q), interfering with antibody binding to the
      CD45RA domain. Overall, we describe the first mutation in PTPRCthat interferes
      with splicing and results in surface expression of a structurally altered CD45
      molecule in humans.

PMID- 12073145
TI  - Baboon placentas express soluble and membrane-bound Paan-AG proteins encoded by
      alternatively spliced transcripts of the class Ib major histocompatibility
      complex gene, Paan-AG.
AB  - The human class Ib major histocompatibility complex (MHC) molecule, HLA-G, is
      unique in its limited polymorphism, high expression in the placenta and
      generation of multiple transcripts by alternative splicing. The proteins encoded
      by these transcripts are believed to modulate maternal-fetal immunological
      relationships during pregnancy. The baboon placenta contains messages encoded by
      a novel MHC gene, Paan-AG, which is evolutionarily related to the HLA-A locus,
      but shares unique characteristics with HLA-G. In this study, we show that the
      Paan-AG message is alternatively spliced to generate at least seven transcripts.
      One of these transcripts retains intron 4 and encodes a soluble glycoprotein with
      three external domains and a unique 21-amino-acid sequence at the carboxyl
      terminus, similar to soluble HLA-G1. This glycoprotein was detected in first
      trimester placental villous cytotrophoblast and syncytiotrophoblast, and in
      extravillous cytotrophoblast cells in the basal plate in term placenta. Four of
      the transcripts ( Paan-AG1, Paan-AG2, Paan-AG3, Paan-AG4) encode membrane-bound
      class Ib MHC glycoprotein isoforms. Paan-AG1 protein expression was similar to
      that of sPaan-AG, while Paan-AG2 protein was not detected in these tissues. The
      other two transcripts ( Paan-AGx and Paan-AGxi) contain a truncated exon 3 and
      multiple stop codons. Paan-AG1 and Paan-AGx transcripts were detected in a number
      of non-placental tissues, but these transcripts contained multiple stop codons.
      Because of the structural similarities and common features of organ-specific
      expression and splicing of the message, studies on Paan-AG may be of value in
      dissecting the functions of the class Ib proteins in human pregnancy.

PMID- 12073146
TI  - Mouse genetic model for clinical and immunological heterogeneity of
      leishmaniasis.
AB  - Systematic assessment of the role of host genes in clinico-pathological and
      immunological manifestations of Leishmania major-induced disease in mice was
      performed using 20 recombinant congenic (RC) strains. As the RC strains are
      homozygous and each carries a different, random set of 12.5% genes from the
      resistant strain, STS/A, and 87.5% genes from the susceptible strain, BALB/cHeA,
      they allowed us to study the pathological and immunological characteristics of
      infected hosts in 20 fixed different random combinations of BALB/c and STS genes.
      The 20 RC strains differ widely in expression of different symptoms of disease
      and in immunological characteristics. Disease or healing in different strains
      occurred in association with different components of immune response -- with the
      exception of a frequently occurring correlation between the disease and IgE
      levels. Moreover, some parameters of the immune response were highly correlated
      in some strains but not at all in others. This shows that several patterns of the
      immune response may be associated with the same clinical outcome, depending on
      the host genotype. Our data also suggest that despite the complexity of
      regulation, when a sufficient number of controlling loci is known, the prediction
      of a phenotype is possible. Combining functional and clinical information with
      multilocus genotyping may improve our ability to predict the progression of the
      disease and to optimize the treatment.

PMID- 12073147
TI  - Major histocompatibility complex controls susceptibility and dominant
      inheritance, but not the severity of the disease in mouse models of rheumatoid
      arthritis.
AB  - Collagen-induced arthritis (CIA) in DBA/1 and proteoglycan-induced arthritis
      (PGIA) in BALB/c mice are the most frequently used mouse models for studying
      clinical, immunological and genetic factors contributing to rheumatoid arthritis.
      DBA/1 ( H2(q)) mice are susceptible to CIA but resistant to PGIA, whereas BALB/c
      mice ( H2 (d)) are susceptible to PGIA and resistant to CIA. To gain insight into
      the mechanisms of how the major clinical (disease susceptibility, severity and
      onset of arthritis) and immunological traits (antigen-specific T- and B-cell
      responses) are influenced by the major histocompatibility complex (MHC), we have
      generated a unique intercross of BALB/c and DBA/1 parent strains, and the F1 and
      F2 hybrids were immunized for either CIA or PGIA. The major clinical and
      immunological traits were identified as either binary (qualitative) or
      quantitative traits on Chromosome 17 with a peak at MHC when the entire
      population was analyzed. In contrast, when only arthritic (susceptible) mice were
      selected and analyzed, the major clinical traits (severity and onset) 'lost' the
      linkage to MHC. Thus, MHC dictates disease susceptibility, but not the severity
      of arthritis. This was even more evident in the case of the H2(q) allele, which
      was clearly responsible for the dominant inheritance of arthritis in F2 hybrids
      (either CIA or PGIA). In conclusion, while certain MHC alleles strongly affect
      disease susceptibility and determine the mode of inheritance of a polygenic
      autoimmune disease, neither the type of inheritance (dominant vs recessive) nor
      other MHC components have evident effects upon the clinical symptoms of
      arthritis.

PMID- 12073148
TI  - Structures of two major histocompatibility complex class I genes of the rainbow
      trout (Oncorhynchus mykiss).
AB  - Here we describe two rainbow trout major histocompatibility complex (MHC) class I
      genes characterized from lambda phage genomic clones prepared from a single fish.
      Clone GC71 contains all exons except a leader peptide-encoding exon. An open
      reading frame is maintained, and thus the gene MhcOnmy-U71 could be expressed in
      this individual. The class I gene found on clone GC41 lacks exons encoding the
      leader peptide and cytoplasmic domain. This gene, MhcOnmy-U41p, is a pseudogene
      due to a deletion in the alpha(2) domain-encoding exon causing premature
      termination. Both the Onmy-U71 and Onmy-U41p genes are distinguished by long
      introns between the exons encoding the alpha(1) and alpha(2) domains. Clone GC41
      also contains the 3' exons of the LMP7/ PSMB8 gene encoding the gamma-interferon
      induced proteosome subunit of rainbow trout.

PMID- 12073149
TI  - Molecular cloning and expression analysis of tumor necrosis factor alpha from a
      marine fish reveal its constitutive expression and ubiquitous nature.
AB  - The tumor necrosis factor alpha ( TNF alpha) gene from the marine fish, gilthead
      seabream (Sparus aurata L.), has been isolated by RT-PCR using degenerate primers
      designed against vertebrate TNF alpha conserved motifs and subsequent rapid
      amplification of cDNA ends (RACE). The TNF alpha cDNA consists of a 142 bp 5'
      untranslated region (5'UTR), a single open reading frame of 762 bp, which could
      code for a 253 amino acid protein, and a 476-bp 3'UTR. The protein sequence
      deduced from seabream TNF alpha gene shows a high degree of homology with the
      Japanese flounder TNF alpha (65.6% identity and 78.9% similarity) and, more
      important, it is more homologous to mammalian TNF alphas (41.1-48.6% similarity)
      than to TNF betas (36.0-43.5% similarity). The prediction of a transmembrane
      domain between residues 37 and 54 of seabream TNF alpha and the presence of a
      conserved Thr-Leu sequence, which is associated with cleavage of the mouse TNF
      alpha molecule, suggest that seabream TNF alpha exists in two forms, a membrane
      bound and a soluble form. RT-PCR shows that the seabream TNF alpha messenger was
      widely and constitutively accumulated. Lastly, stimuli known to up-regulate
      seabream IL-1 beta, lipopolysaccharide and lymphocyte-derived macrophage
      activating factor, failed to up-regulate TNF alpha in cultured macrophages. The
      putative role of three AU-rich endotoxin-responsive motifs (AREs) of seabream TNF
      alpha mRNA, found within two phylogenetically conserved protein binding regions,
      is discussed.

PMID- 12073150
TI  - The H2 haplotype regulates the distribution of B cells into B-1a, B-1b and B-2
      subsets.
AB  - The size of B-cell subsets appears to be under genetic control, but the mechanism
      of this regulation is unknown. By analyzing five congenic strains of mice that
      differ only in their H2 haplotype, we addressed the issue of whether the MHC
      genes are involved in the relative proportions of B-1a, B-1b and B-2 cells. Not
      only were there considerable differences in the percentages of B-1 in B cells
      between H2s mice which were the highest [78.5+/-0.8% in the peritoneal cavity
      (PerC), and 26.3+/-0.5% in the spleen] and H2d mice, which were the lowest
      (15.2+/-0.6% in the PerC, and 10.9+/-0.6% in the spleen), but the percentages of
      B-1a cells varied inversely to those of B-1. Crosses between H2s and H2d strains
      showed that the highest B-1 frequencies occurred in F2 progeny expressing the
      homozygous H2s (70.8+/-2.1% in the PerC, and 30.0+/-0.5 in the spleen), and the
      lowest in that expressing the homozygous H2d haplotype (8.9+/-0.6% in the PerC,
      and 8.6+/-0.4% in the spleen). A dose effect of H2 was established in
      heterozygous F1 and F2 mice. As mice aged, there was a reduction of B-1 cells in
      the PerC, at the expense of B-1b in the H2s, but not in the H2d mice. Hence, the
      H2 genes appear to participate in regulating the proportions of B-1a, B-1b and B
      2 cells.

PMID- 12073151
TI  - Linkage of Patr-AL to Patr-A and- B in the major histocompatibility complex of
      the common chimpanzee (Pan troglodytes).
AB  - Patr-AL is a recently described gene found only in the common chimpanzee, but
      closely related in structure to the highly polymorphic Patr-A and HLA-A genes of
      the chimpanzee and human MHCs, respectively. Unlike Patr-A and HLA-A, the Patr-AL
      gene has little polymorphism and is not fixed in the chimpanzee genome. To
      determine whether Patr-AL is located in the MHC or elsewhere, we compared
      segregation of the Patr-AL gene with segregation of Patr-A and - B alleles in
      chimpanzee families. The results demonstrate that Patr-AL is an MHC class I gene
      present on different MHC haplotypes as defined by their combination of Patr-A and
      B alleles.

PMID- 12073152
TI  - Molecular characterization of bovine CD26 upregulated by a staphylococcal
      superantigen.
AB  - In this report, we describe the cloning, sequencing, and expression of the bovine
      orthologue of CD26 (BoCD26). Several monoclonal antibodies specific for a
      molecule, activation molecule 3 (ACT3), aberrantly expressed on superantigen
      stimulated bovine CD8(+) lymphocytes, reacted with recombinant BoCD26 expressed
      in COS-7 and CHO cells. We also showed that human CD8(+) T cells stimulated by a
      superantigen expressed CD26 at high levels. These results demonstrate that ACT3
      is identical to BoCD26 and suggest that CD26 upregulation on CD8(+) T cells is a
      general phenomenon of superantigens and not limited to their effects on bovine
      cells.

PMID- 12073153
TI  - Investigation of the genetic influence of the OPG, VDR (Fok1), and COLIA1 Sp1
      polymorphisms on BMD in the Irish population.
AB  - Low bone mineral density (BMD) is a major risk factor for the development of
      osteoporosis and there is strong evidence to suggest that the procurement and
      preservation of peak BMD is genetically determined. In an effort to identify
      factors responsible for susceptibility to low BMD in the Irish population, we
      investigated its possible association with polymorphisms in the Osteoprotegerin
      (OPG) gene, Type I collagen alpha 1 (COLIA1) Sp1 binding site and vitamin D
      receptor (VDR) start codon. Following a systematic screening of the regulatory
      and coding regions of the OPG gene, we identified a novel G1181C polymorphism in
      exon 1 and a T950C polymorphism in the promoter region of the OPG gene.
      Participants were recruited from the Bone Densitometry Unit of Cork University
      Hospital, including 381 postmenopausal women aged 61.26 +/- 8.50 (mean +/- SD)
      and 130 premenopausal women aged 46.30 +/- 6.50 (mean +/- SD). Following
      association analysis using both the premenopausal and postmenopausal cohorts we
      found that postmenopausal women carrying one or more C alleles of the G1181C
      polymorphism had 14.8% lower BMD (P = 0.05) at the lumbar spine and 14.4% lower
      BMD (P = 0.04) at the FN. However, both were nonsignificant when the Bonferroni
      correction factor (0.01 significance level) was applied to correct for multiple
      hypothesis testing. We found no association between alleles of the T950C OPG
      polymorphism and BMD. Similarly, we have found a lack of association between the
      VDR (fok1) polymorphism or COLIA1 Sp1 polymorphism and low BMD in either
      postmenopausal or premenopausal women in this population.

PMID- 12073154
TI  - A comparison of alfacalcidol and menatetrenone for the treatment of bone loss in
      an ovariectomized rat model of osteoporosis.
AB  - We conducted this study to evaluate the characteristic effects of alfacalcidol
      (ALF) and menatetrenone (VK) in preventing bone loss using an ovariectomized rat
      model of osteoporosis. Bilateral ovariectomy (OVX) or sham operation was
      performed on 10-month-old female Wistar rats. OVX caused a significant decrease
      in the bone mass and the mechanical strength of the lumbar vertebra as well as
      the femur 6 months after surgery. VK treatment (30 mg/kg, food intake) required a
      6-month period to prevent the bone loss induced by estrogen deficiency, whereas
      ALF (0.1 or 0.2 mg/kg, p.o.) increased the bone mass and the mechanical strength
      of the lumbar vertebra as well as the femur in a 3-month treatment period, far
      above the level in the sham-operated rats. Neither ALF or VK caused
      hypercalcemia, despite administration for as long as 6 months. By doing a micro
      CT analysis of the vertebral trabecular microstructure, it was revealed that ALF
      treatment increased the interconnections and the plate-like structures and that
      VK significantly increased the trabecular number. It was also indicated that the
      increase in spinal strength by ALF treatment was closely associated with
      improvement of the microstructure, but not VK. The results of histomorphometric
      analysis showed that ALF caused a significant suppression of bone resorption yet
      maintained formation in the endocortical perimeter, and also stimulated bone
      formation in the periosteal perimeter, thereby causing an increase in cortical
      area. No marked effect of VK on histomorphometric parameters was observed,
      whereas VK as well as ALF maintained the material strength at femoral midshaft of
      the normal level, suggesting that VK affected bone quality and thereby prevented
      the decrease in mechanical strength of femur caused by OVX. In conclusion, it was
      demonstrated that the two drugs, ALF and VK, differed markedly in their potency
      and mechanisms for improving bone strength. These results have important
      implications in understanding the characteristic actions of vitamin K and active
      vitamin D on bone metabolism.

PMID- 12073155
TI  - Ultrastructure of forming enamel in mouse bearing a transgene that disrupts the
      amelogenin self-assembly domains.
AB  - The mouse X-chromosomal amelogenin gene promoter was used to drive the expression
      of mutated amelogenin proteins in vivo. Two different transgenic mouse lines
      based on deletions to either the amino-terminal (A-domain deletions) or to the
      carboxyl-region (B-domain deletions) were bred. In the molars of newborn A-domain
      deleted transgenic mice the formation of the initial layer of aprismatic enamel
      was delayed. There were severe structural alterations in the enamel of incisors
      of newborn mice bearing the A-domain deletion which were not apparent in animals
      bearing the B-domain deletion. In the A-domain-deleted animals, stippled material
      accumulated throughout the entire thickness of the forming enamel apparently
      causing a disruption of the normal rod-to-inter-rod relationship. This stippled
      material was likened to and interpreted as being groupings of amelogenin
      nanospheres. In the B-domain-deleted animals the stippled material was detected
      only in minute defects of the forming enamel. These data suggest significant
      differences in nanosphere assembly properties for animals bearing either the A
      domain or the B-domain-deleted transgene. The present in vivo experimental
      approach suggests that at early stages of enamel formation, the A-domain plays a
      greater role than does the B-domain in amelogenin self-assembly, and consequently
      in enamel architecture and structure.

PMID- 12073156
TI  - Serum tartrate-resistant acid phosphatase 5b, but not 5a, correlates with other
      markers of bone turnover and bone mineral density.
AB  - Human serum contains two isoforms of tartrate-resistant acid phosphatase (TRACP)
      known as TRACP 5a and TRACP 5b with pH optima of 5.0 and 5.8, respectively.
      Preliminary data suggest that serum TRACP 5b is derived from osteoclasts and
      serum TRACP 5a from some other cells. It has been reported that heparin inhibits
      TRACP 5a but has no effect on the activity of TRACP 5b. Here we show that heparin
      has no effect on serum TRACP activity, as determined using our previously
      published immunoassay, suggesting that the immunoassay does not detect TRACP 5a.
      The change of serum TRACP 5b activity after 6 months HRT, determined by this
      immunoassay, correlated significantly with the changes of all markers of bone
      turnover determined, including serum N- and C-terminal propeptides of type I
      collagen and urinary-free deoxypyridinoline. Serum TRACP 5b activity was
      significantly elevated in patients with osteoporosis and had a significant
      negative correlation with bone mineral density (BMD). Serum TRACP 5a activity,
      determined by an immunoassay, showed no correlation with serum TRACP 5b activity,
      with BMD, or with any of the markers of bone turnover. These results show that
      serum TRACP 5b, but not 5a, reflects the bone resorption rate, and that our TRACP
      5b immunoassay may be a specific method for the determination of the bone
      resorption rate from serum samples.

PMID- 12073157
TI  - Osteopontin deficiency increases mineral content and mineral crystallinity in
      mouse bone.
AB  - Fourier transform infrared microspectroscopy (FTIRM) and infrared imaging (FTIRI)
      were used to characterize the mineral in bones of two different lines of Opn
      deficient (Opn-/-) mice and their background-matched wild-type controls (Opn+/+).
      Sections of tibia and femur from 12-week-old and 16-week-old mice were evaluated
      with a spatial resolution between 10 microm (FTIRM) and 7 microm (FTIRI). FTIRI
      was used to examine 400 microm x 400 microm areas in cortical bone and trabecular
      bone and FTIRM examined selected 20 microm x 20 microm areas at sites within
      these anatomically defined areas. Despite the absence of an obvious phenotype in
      Opn-deficient mice, being undetectable by radiographic and histological methods,
      FTIRM analyses revealed that the relative amount of mineral in the more mature
      areas of the bone (central cortical bone) of Opn-knockout mice was significantly
      increased. Moreover, mineral maturity (mineral crystal size and perfection)
      throughout all anatomic regions of the Opn-deficient bone was significantly
      increased. The 2-dimensional, color-coded data (images) produced by FTIRI showed
      similar increases in mineral maturity in the Opn-/- bone, however, the
      crystallinity parameters were less sensitive, and significance was not achieved
      in all areas analyzed. Nonetheless, the findings of increased mineral content and
      increased crystal size/perfection in both lines of Opn-deficient mice at both
      ages are consistent with in vitro data indicating that Opn is a potent inhibitor
      of mineral formation and mineral crystal growth and proliferation, and also
      support a role for Opn in osteoclast recruitment and function.

PMID- 12073158
TI  - Bone-protecting effect of safflower seeds in ovariectomized rats.
AB  - Safflower (Carthamus tinctorius L.) seeds have long been clinically used in Korea
      to promote bone formation and prevent osteoporosis. However, the beneficial
      effect has not been scientifically evaluated. Thus, in the present study we
      investigated whether phytoestrogen rich safflower seeds reduce bone loss in
      ovariectomized rats. Female Sprague-Dawley rats were subjected to bilateral
      ovariectomy or sham surgery. One week after the operation, ovariectomized rats
      were either fed a diet containing defatted safflower seeds or injected with 17b
      estradiol (E2) for 4 weeks. As expected, ovariectomy resulted in a dramatic
      reduction in trabecular bone mass of the proximal tibia, increase in deposition
      of marrow fat, and in uterine atrophy. E2 treatment almost completely prevented
      bone loss as well as marrow adiposity, as examined by scanning electron
      microscopy and histomorphometry. Safflower seeds partially prevented ovariectomy
      induced bone loss and slightly reduced marrow adiposity. Safflower seeds, in
      contrast to E2, exerted very weak uterotrophic action. In an attempt to elucidate
      the underlying mechanisms, effect of polyphenolic compounds extracted from
      safflower seeds on proliferation of osteoblast-like cells was also assessed in
      vitro. The mixed polyphenolic compounds stimulated growth of ROS 17/2.8
      osteoblast-like cells in a dose-dependent manner (5-100 mg/ml), as potently as E2
      and genistein. The present data provide the first direct in vivo evidence that
      safflower seeds have a protecting effect on bone loss caused by estrogen
      deficiency, without substantial effect on the uterus. The beneficial effect of
      safflower seeds may be mediated, at least in part, by the stimulating effect of
      polyphenolic compounds on proliferation of osteoblasts.

PMID- 12073159
TI  - Comparison of the subjective effects of Delta(9)-tetrahydrocannabinol and
      marijuana in humans.
AB  - RATIONALE: There has been controversy about whether the subjective, behavioral or
      therapeutic effects of whole plant marijuana differ from the effects of its
      primary active ingredient, Delta(9)-tetrahydrocannabinol (THC). However, few
      studies have directly compared the effects of marijuana and THC using matched
      doses administered either by the smoked or the oral form. OBJECTIVE: Two studies
      were conducted to compare the subjective effects of pure THC to whole-plant
      marijuana containing an equivalent amount of THC in normal healthy volunteers. In
      one study the drugs were administered orally and in the other they were
      administered by smoking. METHODS: In each study, marijuana users (oral study:
      n=12, smoking study: n=13) participated in a double-blind, crossover design with
      five experimental conditions: a low and a high dose of THC-only, a low and a high
      dose of whole-plant marijuana, and placebo. In the oral study, the drugs were
      administered in brownies, in the smoking study the drugs were smoked. Dependent
      measures included the Addiction Research Center Inventory, the Profile of Mood
      States, visual analog items, vital signs, and plasma levels of THC and 11-nor-9
      carboxy-THC. RESULTS: In both studies, the active drug conditions resulted in
      dose-dependent increases in plasma THC levels, and the levels of THC were similar
      in THC-only and marijuana conditions (except that at the higher oral dose THC
      only produced slightly higher levels than marijuana). In both the oral study and
      the smoking study, THC-only and whole plant marijuana produced similar subjective
      effects, with only minor differences. CONCLUSION: These results support the idea
      that the psychoactive effects of marijuana in healthy volunteers are due
      primarily to THC.

PMID- 12073161
TI  - Adenosinergic modulation of the discriminative-stimulus effects of
      methamphetamine in rats.
AB  - RATIONALE: A(1) and A(2A) adenosine receptors are co-localized with dopamine D(1)
      and D(2) receptors, respectively, and their stimulation attenuates dopaminergic
      functioning. OBJECTIVE: To test whether adenosine antagonists with different
      selectivities for A(1) and A(2A) receptors mimic the discriminative-stimulus
      effects of dopamine releaser methamphetamine. METHODS: Effects of the A(1)
      antagonist DPCPX, the preferential A(2A) antagonist DMPX and the non-selective
      adenosine antagonist caffeine were evaluated in Sprague-Dawley rats trained to
      discriminate 1.0 mg/kg, IP, methamphetamine from saline under a fixed-ratio 10
      schedule of food presentation. RESULTS: The A(1) antagonist DPCPX (1.0-10.0
      mg/kg) failed to substitute for methamphetamine. However, 5.6 mg/kg DPCPX shifted
      the methamphetamine dose-response curve to the left. The A(2A) antagonist DMPX
      (1.8-18.0 mg/kg) produced about 70% methamphetamine-appropriate responding and
      the non-selective antagonist caffeine (3.0-56.0 mg/kg) about 50% methamphetamine
      appropriate responding at the highest tested doses. Both DMPX (5.6 mg/kg) and
      caffeine (30.0 mg/kg) shifted the methamphetamine dose-response curve to the
      left. Methamphetamine-like effects of DMPX were blocked fully by the D(2)
      antagonist spiperone (0.18 mg/kg) and partially by the D(1) antagonist SCH-23390
      (0.018 mg/kg). CONCLUSIONS: Antagonism at A(2A) adenosine receptors directly
      mimics the discriminative-stimulus effects of methamphetamine through the
      interaction with dopamine receptors. Antagonism at A(1) adenosine receptors
      potentiates effects of lower methamphetamine doses and thus plays a rather
      indirect, modulatory role.

PMID- 12073160
TI  - Effects of melatonin on orofacial movements in rats.
AB  - RATIONALE: While reserpine-induced oral movements (OM), an animal model of
      tardive dyskinesia, are more persistent in old than in adult rats, old animals
      present spontaneous OM, which are phenomenologically similar to those presented
      by reserpine-treated adult rats. We postulate that these OM may be the result of
      oxidative stress induced by both age and reserpine treatment. OBJECTIVES: We
      intended to determine the preventative effects of exogenous melatonin (one of the
      most important endogenous antioxidants) as well as suppression of endogenous
      melatonin via continuous exposure to light on reserpine- or age-induced OM in
      rats. METHODS: Adult (4 months of age) male Wistar rats were repeatedly treated
      with saline or melatonin (5 mg/kg, IP) and saline or reserpine and kept under a
      12-h light/dark cycle for quantification of reserpine-induced OM as well as
      oxidative stress (via quantification of lipid peroxidation). To verify the
      effects of endogenous melatonin suppression on reserpine-induced OM, adult rats
      were repeatedly treated with saline or reserpine and continuously exposed to
      light. To verify the effects of exogenous melatonin on age-induced OM older (20
      months of age) rats were long-term treated with saline or melatonin and kept
      under a 12-h light/dark cycle. RESULTS: Melatonin attenuated both reserpine- and
      age-induced OM. Reserpine enhanced striatal lipid peroxidation, that was
      prevented by melatonin co-administration. Continuous exposure to light increased
      spontaneous as well as reserpine-induced OM, indicating that endogenous melatonin
      may be involved in this movement disorder. CONCLUSIONS: We suggested that
      melatonin attenuates both reserpine- and age-induced OM in rats.

PMID- 12073162
TI  - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and its stereoisomers as
      reinforcers in rhesus monkeys: serotonergic involvement.
AB  - RATIONALE: The reinforcing effects of MDMA and its enantiomers have not been
      extensively characterized in laboratory animals. OBJECTIVES: To investigate
      whether MDMA and its stereoisomers would be self-administered intravenously by
      rhesus monkeys ( Macaca mulatta), and to assess the effects of serotonin(2)
      receptor antagonists on MDMA-maintained responding. METHODS: Four adult male
      rhesus monkeys were maintained on a fixed ratio 10, time-out 60-s schedule for
      0.01 mg/kg cocaine or saline injections. Racemic MDMA and its stereoisomers, and
      racemic methamphetamine were periodically substituted for cocaine or saline. In
      subsequent antagonist experiments, five adult rhesus monkeys (three male, two
      female) were maintained on a multiple dose fixed ratio 30, time-out 45-s schedule
      for cocaine or saline injections. Racemic MDMA and its enantiomers were
      periodically substituted for cocaine or saline, with or without a pre-session
      injection of the serotonin(2) receptor antagonists ketanserin or MDL100907.
      RESULTS: In the initial self-administration experiments, MDMA and its
      stereoisomers generated "inverted U"-shaped self-administration curves across the
      dose range tested. Racemic MDMA doses between 0.01 and 0.1 mg/kg per injection,
      S(+)-MDMA doses between 0.003 and 0.1 mg/kg per injection, and R(-)-MDMA doses
      between 0.01 and 0.1 mg/kg per injection engendered more responding than saline;
      however, no dose of any form of MDMA maintained as much behavior as cocaine or
      methamphetamine. In subsequent antagonist experiments, pretreatments with 0.1 or
      0.3 mg/kg ketanserin or MDL100907 attenuated responding for S(+)-MDMA, and
      completely abolished responding for R(-)-MDMA, but did not affect cocaine
      maintained behavior. CONCLUSIONS: MDMA and its stereoisomers serve as reinforcers
      in rhesus monkeys. We suggest that stimulation of 5-HT(2A) receptors is integral
      to the reinforcing effects of MDMA.

PMID- 12073163
TI  - L-5-hydroxytryptophan induced increase in salivary cortisol in panic disorder
      patients and healthy volunteers.
AB  - BACKGROUND: Hypersensitivity of brain serotonin receptors has been proposed as a
      causal mechanism in the pathophysiology of panic disorder. This theory can be
      tested, using serotonergic stimulation of the HPA axis. Up to now, plasma
      cortisol has generally been used as the outcome measure in such studies.
      Assessment of salivary cortisol is a non-invasive alternative to measure HPA axis
      activity. METHOD: Salivary cortisol levels were measured in 24 panic disorder
      patients and 24 healthy volunteers, following ingestion of 200 mg L-5
      hydroxytryptophan or placebo. RESULTS: A significant rise in cortisol was
      observed in both patients and controls following ingestion of L-5
      hydroxytryptophan. No such effects were seen in the placebo condition.
      CONCLUSION: The results show that L-5-hydroxytryptophan stimulated salivary
      cortisol is a useful probe of serotonin function in healthy volunteers as well as
      panic disorder patients, and provide some evidence against a serotonin receptor
      hypersensitivity in panic disorder.

PMID- 12073164
TI  - Low doses of dizocilpine block the development and subsequent expression of
      locomotor sensitization to nicotine in rats.
AB  - RATIONALE AND OBJECTIVES: We attempted to determine if the effects of the
      glutamate NMDA receptor blocker dizocilpine (MK-801) on nicotine locomotor
      sensitization were due to a blockade of the development of sensitization or to
      state-dependency. METHODS AND RESULTS: In experiment 1, repeated co
      administration of a high dose of dizocilpine (0.25 mg/kg) along with 0.4 mg/kg
      nicotine enhanced locomotion, failed to alter the development of locomotor
      sensitization to nicotine, but completely blocked the subsequent expression of
      sensitization to a challenge injection of nicotine alone. However, repeated
      injections of this dose of dizocilpine alone produced locomotion and
      sensitization that was equivalent to that produced by the dizocilpine/nicotine
      combination. In four separate replications in experiments 2 and 3, co
      administration of a low dose of dizocilpine (0.075 mg/kg), which did not produce
      sensitization to itself, blocked both the development of nicotine sensitization
      and its subsequent expression in response to a challenge injection of nicotine.
      Moreover, this repeated dizocilpine/nicotine administration did not affect the
      subsequent development of sensitization to nicotine alone (experiment 3).
      Suggesting that these effects of dizocilpine may be confined to the development
      of sensitization, challenge injections of dizocilpine failed to block the
      capacity to express previously nicotine-sensitized locomotion (experiment 2).
      CONCLUSIONS: Co-administration of a low dose of dizocilpine can block the
      development of locomotor sensitization to repeated injections of nicotine without
      producing state-dependency. Thus, NMDA receptor activation appears to be critical
      for the development, but not the subsequent expression, of nicotine locomotor
      sensitization.

PMID- 12073165
TI  - Prenatal ethanol exposure in rats alters serotonergic-mediated behavioral and
      physiological function.
AB  - RATIONALE: Animals prenatally exposed to ethanol (ethanol-exposed animals)
      exhibit physiological and behavioral abnormalities consistent with altered 5
      hyrdroxytryptamine (5-HT) function including lack of response inhibition and
      increased anxiety and aggression. OBJECTIVE: The present study investigated the
      possibility that ethanol-exposed animals show alterations in 5-HT(1A) and 5
      HT(2A) receptor function, two 5-HT receptor subtypes mediating these behaviors.
      We measured the physiological and behavioral responses to the 5-HT(1A) agonist 8
      hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), and the 5-HT(2A/C)agonist (+/
      )-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride) (DOI), which
      provide indices for estimating central changes in 5-HT activity and receptor
      function. METHODS: Female and male offspring from ethanol-exposed (E), pair-fed
      control (PF), and ad-libitum-fed control (C) dams were tested in adulthood.
      Animals were injected with 8-OH-DPAT or DOI to induce hypothermia and wet-dog
      shakes (WDS, a paroxysmal shudder of the head, neck and trunk), respectively, or
      with saline. In experiment 1, core temperatures were recorded immediately before
      injection of 8-OH-DPAT (0, 0.125 mg/kg or 0.500 mg/kg) and again at 30, 60, 90,
      120 and 180 min post-injection. In experiment 2, the number of WDS were recorded
      in response to injection of DOI (0, 1 mg/kg). RESULTS: E females and males showed
      a greater hypothermic response to 8-OH-DPAT than PF and C animals. E females and
      males also showed less of a differential hypothermic response to low and high
      doses of 8-OH-DPAT than PF and C animals. In addition, in response to DOI, E
      females, but not males, showed a significantly greater rate of WDS than PF and C
      females. CONCLUSIONS: Our findings indicate that prenatal ethanol exposure alters
      5-HT(1A) and 5-HT(2A) receptor function in adulthood and does so in a sex
      specific manner. These findings have important implications for altered hormonal
      and behavioral responsiveness observed in ethanol-exposed animals.

PMID- 12073166
TI  - Study of the addictive potential of modafinil in naive and cocaine-experienced
      rats.
AB  - RATIONALE: Modafinil is a drug that promotes wakefulness and, as such, is used to
      treat hypersomnia and narcolepsy. Preclinical and clinical studies suggest that
      modafinil could possess weak reinforcing effects in drug-experienced subjects.
      However, its abuse potential in drug-naive healthy individuals is still totally
      uninvestigated, despite the fact that availability of modafinil has recently
      increased. OBJECTIVES: The purpose of our study was to investigate the potential
      addictive properties of modafinil by testing its reinforcing effects in naive
      rats. The interactions of modafinil with the reinforcing effects of cocaine were
      also tested. METHODS: First, using i.v. self-administration and place
      conditioning tests, we studied the reinforcing and rewarding effects of a large
      range of doses of modafinil in naive rats. Second, we tested the influence of
      modafinil on reinforcing and incentive effects of cocaine in rats trained for
      cocaine self-administration. The effects of modafinil were compared with those of
      amphetamine and haloperidol. RESULTS: Modafinil did not produce reinforcing or
      rewarding effects and did not modify the effects of cocaine. CONCLUSIONS: Our
      results suggest that modafinil does not possess an addictive potential in naive
      individuals. Furthermore, it would be behaviorally distinct from classical
      central nervous system stimulants which are known to alter cocaine-induced
      effects. However, as shown previously in nonhuman primates and in humans,
      modafinil could possibly have reinforcing effects in cocaine-experienced
      individuals.

PMID- 12073168
TI  - Relief of serotonin selective reuptake inhibitor induced sexual dysfunction with
      low-dose mianserin in patients with traumatic brain injury.
AB  - RATIONALE: Serotonin selective reuptake inhibitors (SSRI) are commonly used in
      the treatment of many psychiatric disorders. Although possessing a relatively
      mild side effect profile, these drugs can cause a number of difficulties,
      including sexual dysfunction. A variety of strategies have been reported in the
      management of SSRI-induced sexual dysfunction, including dose reduction, drug
      holidays, substitution of another antidepressant drug, and various augmentation
      strategies, including use of sildenafil citrate (Viagra), buspirone, and others.
      OBJECTIVES: We aimed to examine the effect of adding another medication,
      mianserin, a mainly postsynaptic serotonin 2A agonist, to ongoing SSRI treatment
      in order to alleviate sexual side effects caused by SSRIs. METHODS: The patients
      included in this study suffered from traumatic brain injury and from psychiatric
      complications that necessitated the use of SSRIs. Seventeen patients were
      included in this study, all were being treated with SSRIs, and all complained of
      sexual dysfunction. Mianserin was added to on-going treatment at low doses, 7.5
      15 mg/day. Patients were followed for at least 3 months. RESULTS: Fifteen of the
      17 patients (88%) included in this study reported improvement in sexual
      dysfunction following this intervention. Ten (59%) reported that sexual function
      achieved pretreatment level. Five (29%) reported "significant improvement," and
      two (12%) did not respond to this intervention and were given sildenafil citrate,
      with good results. Side effects were minimal and included dry mouth, drowsiness,
      headaches, and agitation. CONCLUSIONS: The use of low-dose mianserin as an add-on
      treatment to SSRIs appears to be an effective and well tolerated intervention for
      sexual dysfunction caused by SSRIs.

PMID- 12073167
TI  - Anxiogenic effects of the CCK(B) agonist pentagastrin in humans and dose
      dependent increase in plasma C-peptide levels.
AB  - RATIONALE: Cholecystokinin type B (CCK(B)) receptor agonists such as pentagastrin
      or CCK-4 have panic-like anxiogenic effects in humans. It has also been shown
      that CCK-4 can stimulate insulin release and thus C-peptide release from
      pancreatic islet cells. Combined, these mechanisms may provide a basis for a
      bioassay. OBJECTIVES: Our aim was to study if a pentagastrin bolus injection
      evokes insulin release (as measured by C-peptide) and if the levels of C-peptide
      correlate to the anxiogenic effect of pentagastrin. METHODS: Pentagastrin was
      given in bolus IV injections to healthy volunteers at increasing doses (0.003,
      0.012, 0.05 and 0.2 microg/kg). RESULTS: A significant increase in the plasma
      level of C-peptide was observed 2-4 min after the highest dose of pentagastrin.
      This increase was accompanied by a transient panic-like anxiety within 2 min
      following pentagastrin, measured using a state anxiety scale. Also, 0.05
      microg/kg pentagastrin gave a minor but significant subjective discomfort at the
      same time interval. The basal plasma level of C-peptide preceding the
      pentagastrin injection showed a positive correlation to the intensity of the
      subsequent pentagastrin-induced panic-like anxiety as rated on the state anxiety
      scale. In addition, basal plasma levels of cortisol were positively correlated to
      the subsequent pentagastrin-induced increase in plasma C-peptide levels.
      CONCLUSIONS: Our results imply a possible relationship between insulin/C-peptide
      release and sensitivity to psychotropic activation by CCK(B) receptor
      stimulation. Furthermore, we postulate that both basal and pentagastrin-induced
      plasma levels of C-peptide may possess characteristic phenotype properties for
      anxiety related traits.

PMID- 12073170
TI  - Reinstatement of cocaine seeking in 129X1/SvJ mice: effects of cocaine priming,
      cocaine cues and food deprivation.
AB  - RATIONALE AND OBJECTIVES: The mechanisms underlying relapse to cocaine seeking
      induced by exposure to priming cocaine injections, cues associated with cocaine
      self-administration and environmental stressors have been studied in rats. Here
      we describe a reinstatement method for studying relapse to cocaine seeking in
      mice, a suitable species for studying the effect of genetic manipulations such as
      gene knockout or gene over-expression on compulsive drug use. METHODS: Male mice
      of the 129X1/SvJ strain were trained for 14-16 days to self-administer cocaine
      (0.75 mg/kg/infusion; 4 h/day; fixed-ratio-1 schedule of reinforcement; infusions
      were paired with a light-tone compound cue). Next, the lever-pressing behavior
      was extinguished by removing the cocaine syringes in the presence (Exps. 1 and 3)
      or absence (Exp. 2) of the cocaine cue. Subsequently, tests for reinstatement
      were conducted after exposure to priming injections of cocaine (0, 1.5, 3.0 and
      6.0 mg/kg, IV; Exp. 1), response-contingent presentations of the cocaine
      associated cue (Exp. 2), or food deprivation stress (1 and 22 h; Exp. 3).
      RESULTS: The effect of cocaine priming on reinstatement was modest and was only
      observed at the highest dose tested. On the other hand, reinstatement of cocaine
      seeking was observed following exposure to the cocaine-associated cue and food
      deprivation stress. CONCLUSIONS: The present data suggest that factors
      contributing to relapse to drugs can be studied in the reinstatement model using
      the common 129X1/SvJ mouse inbred strain.

PMID- 12073169
TI  - Genetic determinants of sensitivity to pentobarbital in inbred mice.
AB  - RATIONALE: We postulated that genetic determinants of different responses to
      pentobarbital (PB) in mice would differ from response to response. OBJECTIVES:
      Mice from 14 standard inbred strains were tested for sensitivity to several
      effects of acute PB. METHODS: Strains were tested for sensitivity to PB-induced
      low-dose stimulation and high-dose depression of locomotor activity, reduced
      rearing, hypothermia, and ataxia assessed on a rotarod, using four doses of PB or
      saline. RESULTS: Strains differed in sensitivity to PB for all responses.
      Correlations among strain means indicated that strain sensitivity to a particular
      effect of PB generalized rather well across doses. Sensitivities to some of the
      different behavioral responses were also significantly correlated. For example,
      strains less sensitive to PB-induced enhanced locomotor activity were also
      significantly more sensitive to the drug's hypothermic effects. Some responses
      were genetically independent. Brain PB concentrations were also determined, and
      appeared to be unrelated to inbred strain drug sensitivities. CONCLUSIONS:
      Overall, these results suggest that there are multiple genetic determinants of
      behavioral sensitivity to PB effects. That is, genetically influenced sensitivity
      to PB is not monolithic, but is somewhat specific to the particular response
      variable studied, a result that also characterizes genetic control of responses
      to other drugs.

PMID- 12073171
TI  - Nucleus accumbens dopamine and discriminated approach learning: interactive
      effects of 6-hydroxydopamine lesions and systemic apomorphine administration.
AB  - RATIONALE: Although dopaminergic mechanisms have been implicated in incentive
      motivational processes, their role in appetitive conditioning remains poorly
      understood. OBJECTIVES: To investigate the effects of dopamine (DA) depleting
      lesions of the nucleus accumbens and the direct acting dopamine receptor agonist
      apomorphine on the learning of discriminated appetitive approach behavior in a
      Pavlovian autoshaping paradigm. METHODS: Rats received bilateral infusions of
      either phosphate-buffered saline (shams) or 6-hydroxydopamine (lesions) directly
      into the nucleus accumbens. Ten days later, rats were trained on an autoshaping
      task whereby a previously neutral light stimulus was paired with food reward.
      Presentation of another stimulus (CS-) was never followed by reward. Over 100
      pairings subjects developed a conditioned response of approaching the reward
      predictive stimulus (CS+). Prior to each autoshaping session subjects were
      administered either saline (1 ml/kg SC) or apomorphine (30 microg/kg; 100
      microg/kg), in a between-subjects design. RESULTS: Lesioned subjects showed a
      delay in the acquisition of discriminated approach and were insensitive to a
      subsequent change in the contingency of the task whereby approaches to the CS+
      now prevented food delivery. Low dose apomorphine profoundly impaired learning in
      both sham and lesioned subjects. Despite increasing the overall number of CS+ and
      CS- approaches, the higher dose of apomorphine allowed discriminated approach in
      sham-operated animals only. CONCLUSIONS: These data are compatible with the
      hypothesis that nucleus accumbens dopamine serves to energize rather than guide
      conditioned approach to appetitive cues. They also support the notion that DA
      inputs in this region confer flexibility of approach to cues predictive of
      reward.

PMID- 12073173
TI  - Self-administration of cocaine: scopolamine combinations by rhesus monkeys.
AB  - RATIONALE: Several halogenated analogs of benztropine (BZT) have previously been
      characterized as potent dopamine (DA) uptake inhibitors with diminished
      reinforcing effects relative to cocaine. In addition to their effects on DA
      uptake, these compounds are potent muscarinic cholinergic antagonists.
      OBJECTIVES: The present experiments were designed to examine the hypothesis that
      the anticholinergic action of the BZT analogs contributes to their relatively low
      levels of self-administration. METHODS: Rhesus monkeys self-administered cocaine
      (0.03 mg/kg per injection, i.v.) under either a fixed-ratio 25 (FR 25; n=5) or
      progressive-ratio (PR; n=5) schedule until stable responding was established.
      Saline, cocaine (0.0003-0.1 mg/kg per injection), scopolamine (0.001-0.1 mg/kg
      per injection), or various combinations of cocaine and scopolamine were then made
      available for self-administration. RESULTS: Cocaine maintained dose-related self
      administration under both schedules whereas scopolamine did not. In the majority
      of cases, combinations of cocaine and scopolamine maintained less self
      administration than cocaine alone. CONCLUSIONS: This study supports the
      hypothesis that anticholinergic actions contribute to the diminished self
      administration of BZT analogs relative to cocaine. The mechanism may involve
      antagonism of the reinforcing effect of cocaine and/or punishment of the self
      administration response by the addition of an anticholinergic component of
      action.

PMID- 12073172
TI  - Deficits in reward sensitivity in a neurodevelopmental rat model of
      schizophrenia.
AB  - RATIONALE: Neonatal ventral hippocampal lesions in rats have been shown to result
      in behavioral abnormalities at adulthood thought to simulate some aspects of
      positive and cognitive deficits classically observed in schizophrenic patients.
      OBJECTIVES: We investigated whether such lesions can also induce deficits in
      reward sensitivity that are related to the negative symptoms of psychotic
      disorders. METHODS: To investigate the effects of neonatal and adult lesions of
      the ventral hippocampus on reward-related behaviors we used the conditioned place
      preference (CPP) test and the saccharin consumption model. RESULTS: In contrast
      to adult-lesioned animals, neonatally lesioned rats exhibited a deficit in
      amphetamine-induced CPP and a significant reduction in saccharin preference.
      These deficits are unlikely due to lesion-induced motor impairments as both
      neonatal- and adult-lesioned rats exhibited a similar hyperlocomotor response to
      amphetamine. CONCLUSIONS: Taken together, these results show that neonatal
      ventral hippocampal lesions induce a reduction in reward-seeking behaviors in
      adulthood that mimic some aspects of the negative symptoms (anhedonia) in
      psychotic patients.

PMID- 12073175
TI  - Venous thromboembolism epidemiology: implications for prevention and management.
AB  - Venous thromboembolism is a major health problem, with an incidence that exceeds
      1 per 1000. Over 200,000 new cases occur in the United States annually. Of these,
      30% of patients die within 30 days; one-fifth suffer sudden death due to
      pulmonary embolism. Despite improved prophylaxis, the incidence of venous
      thromboembolism has not changed significantly since 1980. Independent risk
      factors for venous thromboembolism include increasing age, male gender, surgery,
      trauma, hospital or nursing home confinement, malignancy, neurologic disease with
      extremity paresis, central venous catheter/ transvenous pacemaker, prior
      superficial vein thrombosis, and varicose veins; among women, the risk factors
      include pregnancy, oral contraceptives, and hormone replacement therapy. About
      30% of surviving patients develop recurrent venous thromboembolism within 10
      years. Independent predictors for recurrence include increasing age, obesity,
      malignant neoplasm, and extremity paresis. About 28% of patients develop venous
      stasis syndrome within 20 years. To reduce venous thromboembolism incidence,
      improve survival, and prevent recurrence and complications, patients with these
      characteristics should receive appropriate prophylaxis.

PMID- 12073176
TI  - Selective inhibition of coagulation factors: advances in antithrombotic therapy.
AB  - Heparin and coumarin derivatives have long been used for the prophylaxis and
      treatment of venous thromboembolism (VTE). Although they have demonstrated
      efficacy and safety, they act at multiple targets within the coagulation cascade
      and their efficacy is influenced by many patient variables. Because of the need
      to improve the benefit-to-risk ratio of antithrombotic drugs, newer agents that
      target single coagulation factors have been developed. These include selective
      factor Xa inhibitors, direct thrombin inhibitors (DTIs), and inhibitors of factor
      IXa and the factor VII-tissue factor complex. Three DTIs-hirudin, bivalirudin,
      and argatroban-have been approved for clinical use. Fondaparinux, a novel
      pentasaccharide and the first selective factor Xa inhibitor to be approved by the
      U.S. Food and Drug Administration and the European Agency for the Evaluation of
      Medicinal Products, is indicated for the prevention of VTE after major orthopedic
      surgery. Fondaparinux has predictable pharmacokinetics, is almost 100%
      bioavailable, and has a half-life that allows once-daily dosing in all
      indications. In addition, the routine monitoring of standard indicators of
      hemostasis is not required. The availability of these agents and the continued
      development of investigational selective coagulation inhibitors have the
      potential to improve efficacy and decrease adverse events in patients at risk for
      VTE.

PMID- 12073178
TI  - Unresolved issues in the prevention and treatment of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a major health problem. Anticoagulation can
      significantly decrease the morbidity and mortality associated with VTE. Heparin
      and coumarin derivatives have been the standard of care for the last 50 years,
      and the development of low-molecular-weight heparin preparations has
      significantly improved the prevention and treatment of venous thromboembolic
      disease. With these advances, investigators are now able to address some of the
      unresolved issues in antithrombotic therapy, including the search for the optimal
      antithrombotic agent in high-risk patients, the optimal timing of
      thromboprophylaxis initiation in the surgical population, and the duration of
      prophylaxis for the prevention of initial and recurrent VTE events. Clinical
      trials have begun to investigate many of these issues, and the resulting data
      have already contributed to improving the management of patients with a high risk
      of VTE.

PMID- 12073177
TI  - Optimizing prophylaxis of venous thromboembolism.
AB  - Thrombotic events contribute significantly to the morbidity, mortality, and
      health care costs of patients undergoing major orthopedic surgery. Despite
      therapy with unfractionated heparin, low-molecular-weight heparin, or warfarin,
      thrombotic events continue to occur at an unacceptably high rate in populations
      at risk. The need for improved prophylaxis against venous thromboembolism has
      resulted in the development of several new antithrombotics, both recently
      approved and investigational, that target specific steps in the hemostatic
      pathway. These include direct thrombin inhibitors, agents that inhibit the factor
      VIIa-tissue factor complex, and selective factor Xa inhibitors. Fondaparinux is
      the first of the selective factor Xa inhibitors. It was evaluated in the most
      comprehensive drug development program ever in major orthopedic surgery,
      culminating in four phase III trials involving more than 7000 enrollees, and is
      the first agent in its class to be approved by the U.S. Food and Drug
      Administration and the European Agency for the Evaluation of Medicinal Products.
      It has been suggested that fondaparinux's superior efficacy may be related to its
      ability to initiate selective inhibition of factor Xa and its predictable linear
      pharmacokinetics.

PMID- 12073179
TI  - Treatment of symptomatic venous thromboembolism: improving outcomes.
AB  - Antithrombotic therapy with unfractionated heparin (UFH) and warfarin for the
      treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) became
      widely accepted in the early 1960s. Subsequent clinical trials have focused on
      the importance of early intravenous UFH in the treatment of venous thromboembolic
      events, the method of heparin administration, the importance of rapid
      anticoagulation to prevent recurrent venous thromboembolism (VTE), and the
      optimal duration of UFH administration. Low-molecular-weight heparin (LMWH)
      represents a significant advance over UFH therapy for VTE. Developed in the late
      1980s, LMWH has become an excellent alternative to UFH because it offers superior
      efficacy and safety, improved pharmacokinetics, longer half-life, and once- or
      twice-daily subcutaneous administration without the need for laboratory
      monitoring. Fondaparinux is the first of a new class of antithrombotic agents
      that targets factor Xa. Based on studies of the heparin binding site of
      antithrombin, this novel pentasaccharide has superior pharmacokinetics and
      bioavailability when compared with LMWH and can be administered once daily.
      Studies in patients undergoing major orthopedic surgery and in those with
      proximal DVT indicate that the efficacy and safety of fondaparinux may represent
      an improvement over those of LMWH.

PMID- 12073180
TI  - Benefit of selective factor inhibition.

PMID- 12073182
TI  - [Bilateral hand transplantation].
AB  - In March 2000 we performed a bilateral hand transplantation on a 47-year-old
      policeman who had lost both hands in a bomb accident. Although he was fitted with
      myoelectric prostheses, he kept investigating the possibility of hand
      transplantation. The ethical, surgical, medical, legal and human aspects of this
      special kind of reconstruction was discussed in a symposium in Vienna, and it was
      decided to go ahead with it if a suitable candidate presented. The operation was
      successful, the immunosuppressive regimen well-planned and carried out, the post
      operative course without any remarkable events. Under intensive physical therapy,
      the patient gradually but steadily regained sensory and motor functions in his
      hands. Now, two years after the operation, the patient is practically independent
      in the activities of daily living and is able to work at his job.

PMID- 12073183
TI  - [The influence on nerve regeneration by the beta2-receptor agonist clenbuterol].
AB  - PURPOSE: Clenbuterol has shown a neuroprotective action in the central nervous
      system by induction of growth factors after cellular damage. Additionally, the
      atrophy of sceletal muscle is attenuated by the application of Clenbuterol after
      denervation. This experiment was performed to show the influence of Clenbuterol
      on regeneration of peripheral nerves. MEHOD AND MATERIAL: In a rat model, the
      sciatic nerve was transected and microsurgically coaptated. Eight animals in each
      group received a daily oral dosage of 100 microg/kg bodyweight during four,
      respectively six weeks. Two control groups received only drinking water under the
      otherwise same protocol. The assessment was done histologically, morphometrically
      and clinically. The weight ratio of the soleus and extensor digitorum muscles of
      the operated to the contralateral side was measured. RESULTS: The groups treated
      with Clenbuterol showed histologically and morphometrically a significantly
      increased axon count and a better g-ratio. The muscle weight ratio was
      significantly higher in the Clenbuterol group after six weeks and more animals in
      this group were able to spread their toes. CONCLUSION: The oral application of
      Clenbuterol in a rodent model shows a positive influence on nerve regeneration.

PMID- 12073184
TI  - [Problems of the musculoskeletal system in amateur orchestra musicians under
      special consideration of the hand and wrist].
AB  - Studies on professional orchestra musicians have shown a high incidence of
      physical problems mainly on the level of the musculoskeletal system. At the same
      time, the individual instrument groups differ in the types and patterns of
      complaints. So far, no study on amateur orchestra musicians has been conducted.
      We therefore interviewed the 130 members of the "Bayerisches Arzteorchester", all
      members being amateur musicians. The complaints were documented and compared with
      those of professional orchestra musicians. 84 % of the musicians had physical
      problems, 74 % involving the musculoskeletal system. The high string players
      suffered mainly from shoulder-neck problems, cellists and bassists complained of
      neck and lumbar spine problems. Wind players suffered at the spine and woodwind
      players at individual digits. The hand was affected in 39 % of the musicians. The
      complaints voiced by amateur musicians are essentially identical with those found
      in professional musicians.

PMID- 12073185
TI  - [Free microvascular transplantation of parts of the great toe for thumb
      reconstruction].
AB  - PURPOSE/BACKGROUND: A reconstructed thumb has to fulfil the function of
      opposition, pinch-grip, stability, sufficient length, sufficient sensibility, and
      painlessness. Next to pollicisation, these requirements can only be met
      satisfactory by the microvascular free great toe-to-hand transplantation. The
      goal of a thumb reconstruction is a compromise between an optimal functional and
      aesthetic outcome and a minimal morbidity of the donor site. METHOD AND CLINICAL
      MATERIAL: Depending on the extent of the traumatic thumb defect, not only the
      fibular part of the ipsilateral great toe but also its adjacent soft tissue and
      the first web space may be integrated into the vascularized transplant. The
      distal phalanx is reduced in width on its tibial side to integrate the second
      digital nerve to the transplant. The rest of the great toe is covered with the
      remaining sensible tibial flap. RESULTS: From 1993 to 1998, five male patients
      have been operated with the described method of partial great toe transfer and an
      additional deepening of the first web space. All reconstructions passed without
      complications. All patients present with a protective sensibility and a dynamic
      two-point discrimination between 8 and 15 mm. The average strength of the
      reconstructed thumb was 79 %, the strength of pinch-grip 90 % of the healthy
      thumb. CONCLUSION: Thumb reconstruction after traumatic amputation distal to the
      metacarpophalangeal joint can in our hands optimally be managed with free
      microvascular anastomosed parts of the great toe and its adjacent soft tissues.

PMID- 12073186
TI  - [Glomus tumours of the extremities: localisation and operative treatment in 36
      cases].
AB  - Glomus tumours are rare lesions and perhaps for that reason they often pose
      diagnostic difficulties. They are benign tumours first described by Masson in
      1924, and they are derived from the glomus body responsible for blood and
      temperature regulation. In this study, 36 cases were reported out of a total of
      more than 35 000 operations in an eleven-year period. Among them were 23 women
      (average age 51 years) and 13 men (average age 52 years). They were diagnosed
      correctly after a mean period of eight years from onset of symptoms until
      surgery. In women, glomus tumours occurred almost always in the distal phalanx,
      especially in the subungual area, in men without any predisposing localisation.
      Two third of the patients presented with local pain and cold intolerance, and 50
      percent of the patients with subungual localisation had a bluish discoloration
      beneath the nail. In three patients without visible or palpable signs additional
      MRI confirmed the diagnosis. All patients were operated upon in local anaesthesia
      and in a bloodless field. In the cases with subungual localisation, we mostly
      used a transungual triangular incision with good cosmetic results. In 94 % of the
      patients the lesion has been cured, in one case symptoms persisted, and in
      another case recurrence occurred. Conclusion. In patients with severe local pain,
      especially in the distal phalanx, glomus tumours should be considered. In cases
      where no clinical signs can be found, MRI - although not specific - may be
      helpful in establishing the correct diagnosis. The operation can be performed in
      local anaesthesia, bloodless field and in subungual localisation through a
      triangular incision. Recurrences may occur.

PMID- 12073187
TI  - [Necrotising fasciitis caused by streptococcal toxic shock syndrome].
AB  - Between 1994 and 1997, sixteen patients suffering from necrotising soft tissue
      infection were treated at the burn centre of the Division of Reconstructive
      Surgery, University of Zurich. The case of a 47 year old man is presented: He
      suffered from a necrotising fasciitis caused by Streptococcal induced Toxic Shock
      Syndrome (STSS). This example emphasizes the necessity of early diagnosis,
      priority of surgical intervention, and the antibiotic strategy. Necrotising
      fasciitis is a serious disease, caused by a variety of bacteria, which shows a
      high mortality rate, and its frequency was increasing over the last years.

PMID- 12073188
TI  - [Presentation of a simple method of preoperative soft-tissue distraction in
      Dupuytren's contracture grade IV].
AB  - We describe a technique of continuous preoperative soft-tissue distraction in
      Dupuytren's contracture grade IV using an unilateral external fixator which is
      simple to apply. The operative technique and the result are demonstrated.

PMID- 12073189
TI  - [Preoperative Intermittent Pneumatic Soft-Tissue Distraction in Patients with
      severe Dupuytren's Contracture].
AB  - PURPOSE: Evaluation of the outcome of preoperative intermittent pneumatic soft
      tissue distraction (IPD) in patients with severe contractures in Dupuytren's
      disease with special regards on recurrent deformities. METHOD: In a prospective
      study, nine patients with Dupuytren's contracture grade III and IV according to
      the classification of Tubiana were treated with a preoperative intermittent soft
      tissue distraction using a pneumatic extension device followed by a standardized
      operative correction and follow-up program. Sixteen fingers were involved: grade
      I and II four fingers, grade III and IV twelve fingers. Nine fingers - grade III
      and IV seven fingers - in six patients had a recurrent deformity. RESULTS: The
      preoperative reduction of contracture simplifies the surgical treatment.
      Preoperatively using the IPD, the flexion contracture was reduced between 5 and
      60 degrees. With an average of 29 (10 to 60) degrees, the improvement was greater
      in fingers with severe contracture (grade III and IV according to Tubiana) than
      in fingers with a minor contracture averaging 10 (5 to 25) degrees. In fingers
      with recurrent deformity, the reduction of the flexion contracture averaged 27 (5
      to 60) degrees. There were no complications leading to break off of the
      distraction. CONCLUSION: The intermittent pneumatic distraction is a good
      alternative to the method introduced by Messina for preoperative soft-tissue
      distraction in patients with severe Dupuytren's contracture.

PMID- 12073190
TI  - [Severe contracture of the proximal interphalangeal joint in Dupuytren's disease:
      does capsuloligamentous release improve outcome?].
AB  - Purpose. Evaluation of effectiveness of capsuloligamentous release in severe PIP
      joint contractures in Dupuytren's disease. Method. Prospective study to compare
      the clinical outcome of eleven patients with severe contracture of the PIP joint
      due to Dupuytren's disease, in whom an additional capsulotomy was performed to
      reduce a residual flexion contracture of the PIP joint of 20 degree and more
      after release and excision of all diseased fascia, with the outcome of 32
      patients with severe contracture of the PIP joint due to Dupuytren's disease, in
      whom the PIP joint contracture could be reduced by fasciectomy alone.
      Preoperatively all patients had a severe flexion contracture (60 degrees or
      greater) of one PIP joint. All patients underwent standardized operative
      treatment and postoperative extension splinting program for six months. Follow-up
      examinations included assessment of active range of motion at two, four, ten, 16
      and 24 weeks after surgery. Results. In the noncapsulotomy group, preoperative
      contracture averaged 70.6 degrees and intraoperative residual contracture
      averaged 2 degrees. In the capsulotomy group, preoperative contracture averaged
      78.6 degrees. Intraoperative residual contracture averaged 61.8 degrees before
      and 2 degrees after capsulotomy. At the final follow-up examination, PIP joint
      flexion contracture averaged 15 degrees in the noncapsulotomy group compared to
      16 degrees in the capsulotomy group. Conclusion. Residual flexion contracture of
      a PIP joint after release and excision of all diseased fascia in Dupuytren's
      disease can be reduced by capsuloligamentous release. The data of this study
      showed no significant differences in the outcome at the final follow-up
      examination between patients with and without capsulotomy. Therefore, we
      recommend capsulotomy as treatment of residual flexion contracture of the PIP
      joint in Dupuytren's disease.

PMID- 12073191
TI  - [Aneurysmal bone cyst of the fourth metacarpal bone--a case report].
AB  - Aneurysmal bone cysts of the hand skeleton are rare (only 3 to 4 % of all ABC;
      Tillmann and v. Torklus 1966 ) and require a differentiated treatment. In the
      presented case, the fourth metacarpal bone of the right hand was affected
      (Enneking stage 3). On account of its rapid growth, radical excision was
      performed and the resected metacarpal bone was replaced by a bicortical iliac
      crest graft. The bone graft healed in without complications, the functional
      result is satisfactory. On twelve-month follow-up there were no signs of relapse.

PMID- 12073193
TI  - [Aggressive digital papillary adenocarcinoma - case report].
AB  - Digital papillary adenocarcinoma is a rare tumour originating from sweat glands,
      often occurring in digits of the hand or foot. We present the case of a 52-year
      old mechanic with this tumour at the distal phalanx of the middle finger. It was
      primarily excised. After histological verification of the diagnosis, amputation
      and axillary lymphadenectomy was performed. So far, no clinical or histological
      parameters were found to be predictive for recurrence or metastasis. This
      indicates that the originally proposed criteria for distinguishing between benign
      (adenoma) and malignant (adenocarcinoma) do not necessarily predict biologic
      behaviour. As according to the available literature metastases occurred in 14 %
      of the described patients within ten years, we propose an aggressive surgical
      approach consisting of amputation and regional lymph node dissection.

PMID- 12073192
TI  - [Total ulnar nerve paralysis due to acute traumatic aneurysm at the forearm].
AB  - We are reporting a case of complete ulnar nerve paralysis due to compression from
      a false aneurysm located in the distal forearm. The aneurysm developed after the
      patient stabbed himself with a meat hook. The ulnar paralysis developed after a
      14-day period of latency. The diagnosis was made using detailed patient history,
      clinical examination, and a sonogram. Early surgical decompression of the nerve
      led to complete restitution of all functions.

PMID- 12073194
TI  - Pheochromocytoma: specialist cases that all must be prepared to treat?

PMID- 12073195
TI  - Neuroprotection is associated with beta-adrenergic receptor antagonists during
      cardiac surgery: evidence from 2,575 patients.
AB  - OBJECTIVE: To determine the impact of perioperative beta-adrenergic receptor
      (betaAR) antagonist administration on neurologic complications. DESIGN:
      Observational database analysis. SETTING: A clinical investigation at a single
      tertiary academic medical center. PARTICIPANTS: Elective coronary artery bypass
      graft surgical patients operated on in the period 1994-1996. INTERVENTIONS:
      Patients were divided into 2 groups: (1) patients given betaAR antagonist
      blocking drugs in the perioperative period, including during operation, and (2)
      patients not given betaAR antagonists. MEASUREMENTS AND MAIN RESULTS: betaAR
      antagonist use in 2,575 consecutive patients undergoing coronary artery bypass
      graft surgery (1994-1996) was determined using the Cardiovascular Database and
      Anesthesia Information System Database. Outcome variables were postoperative
      stroke, coma, and transient ischemic attack. Of patients, 113 (4.4%) had
      postoperative neurologic complications, including stroke (n = 44), coma (n = 12),
      and transient ischemic attack (n = 3). Of patients, 2,296 (89%) received
      perioperative betaAR antagonist therapy, and 279 (11%) did not. Adverse
      neurologic events occurred in 3.9% (n = 90) of patients who received
      perioperative betaAR antagonists and 8.2% (n = 23) of patients who did not
      receive betaAR antagonists (odds ratio, 0.45; 95% confidence interval, 0.28 to
      0.73; p = 0.003, unadjusted.) Severe neurologic outcomes (stroke and coma)
      occurred in 1.9% (n = 44) of patients who received betaAR antagonists and 4.3% (n
      = 12) of patients who did not receive betaAR antagonists (odds ratio, 0.43; 95%
      confidence interval, 0.23 to 0.83; p = 0.016). CONCLUSION: Use of beta-adrenergic
      antagonists was associated with a substantial reduction in the incidence of
      postoperative neurologic complications. A prospective randomized trial is needed
      to verify this potentially important neuroprotective strategy in cardiac surgery.

PMID- 12073196
TI  - Risk factor analysis of early and delayed cerebral complications after cardiac
      surgery.
AB  - OBJECTIVE: To report the incidence, severity, and possible risk factors for early
      and delayed cerebral complications. DESIGN: Retrospective study. SETTING:
      Linkoping University Hospital, Sweden. PARTICIPANTS: Consecutive patients who
      underwent cardiac surgery in the period July 1996 through June 2000 (n = 3,282).
      INTERVENTIONS: A standard cardiopulmonary bypass (CPB) technique was used for
      most patients. Postoperative anticoagulant treatment included heparin or anti-Xa
      dalteparin. Patients undergoing coronary artery bypass graft surgery received
      acetylsalicylic acid, and patients undergoing valve surgery received warfarin.
      MEASUREMENTS AND MAIN RESULTS: Cerebral complications occurred in 107 patients
      (3.3%). Of these, 60 (1.8%) were early, and 33 (1.0%) were delayed, and in 14
      (0.4%) patients the onset was unknown. There were 37 variables in univariate
      analysis (p < 0.15) and 14 variables in multivariate analysis (p < 0.05)
      associated with cerebral complications. Predictors of early cerebral
      complications were older age, preoperative hypertension, aortic aneurysm surgery,
      prolonged CPB time, hypotension at CPB completion and soon after CPB, and
      postoperative arrhythmia and supraventricular tachyarrhythmia. Predictors of
      delayed cerebral complications were female gender, diabetes, previous
      cerebrovascular disease, combined valve surgery and coronary artery bypass graft
      surgery, postoperative supraventricular tachyarrhythmia, and prolonged ventilator
      support. Early cerebral complications seem to be more serious, with more
      permanent deficits and a higher overall mortality (35.0% v 18.2%). CONCLUSION:
      Most cerebral complications had an early onset. The results of this study suggest
      that aggressive antiarrhythmic treatment and blood pressure control may imfurther
      prove the cerebral outcome after cardiac surgery.

PMID- 12073197
TI  - Sodium nitroprusside-induced, but not desflurane-induced, hypotension decreases
      myocardial tissue oxygenation in dogs anesthetized with 8% desflurane.
AB  - OBJECTIVE: To compare sodium nitroprusside (SNP)-induced hypotension with
      desflurane-induced hypotension for the effects on myocardial blood flow and
      tissue oxygenation in dogs. DESIGN: Prospective, randomized, crossover,
      nonblinded. SETTING: University teaching hospital. PARTICIPANTS: Male nonpurpose
      bred hounds (n = 8). INTERVENTIONS: Dogs were anesthetized with 8% desflurane.
      Catheters were inserted into the femoral artery and coronary sinus. A flow probe
      was placed in the left anterior descending (LAD) branch of the coronary artery. A
      sensor that measured myocardial oxygen pressure (PmO(2)) was inserted into the
      myocardium of the left ventricle. Myocardial oxygen consumption (MVO(2)) was
      calculated as LAD flow x arterial - coronary sinus oxygen content. MEASUREMENTS
      AND MAIN RESULTS: Measurements were made at baseline blood pressure levels of 99
      mmHg (measure 1), during hypotension to 62 to 66 mmHg using intravenous SNP or
      14% desflurane (measure 2), and during SNP or 14% desflurane with blood pressure
      support using phenylephrine (measure 3). Each dog randomly received both
      hypotensive treatments, separated by 1 hour. Baseline measures were PmO(2) = 46
      +/- 9 mmHg, LAD flow = 43 +/- 11 mL/min, and MVO(2) = 2.47 +/- 0.73 mL O(2)/min.
      During hypotension induced with SNP, PmO(2) decreased 30% (p < 0.05), LAD flow
      increased 40% (p < 0.05), and MVO(2) did not change. During hypotension induced
      with 14% desflurane, PmO(2) did not change, and LAD flow and MVO(2) decreased 25%
      and 40% (p < 0.05). Blood pressure support with phenylephrine increased LAD flow
      and MVO(2) but did not change PmO(2) during SNP or 14% desflurane treatment.
      CONCLUSION: SNP-induced hypotension produced myocardial vasodilation, but tissue
      oxygenation was impaired. PmO(2) was maintained during desflurane-induced
      hypotension.

PMID- 12073198
TI  - Renal tubular injury after infrarenal aortic aneurysm repair.
AB  - OBJECTIVE: To investigate markers of tubular injury (glutathione-S-transferase
      [GST] isoforms) as early markers for renal damage in patients undergoing
      abdominal aortic aneurysm repair. DESIGN: Prospective study. SETTING: Regional
      teaching hospital. PARTICIPANTS: Eight consecutive patients undergoing elective
      infrarenal abdominal aortic aneurysm repair. INTERVENTIONS: All patients received
      a standard anesthetic technique including a dopamine infusion (3 microg/kg/min)
      but without supplemental renoprotective agents. Urine and blood samples were
      taken at induction, at 1 hour and 3 hours after limb reperfusion, and on days 1
      and 2 postoperatively. Urine microalbumin and creatinine concentrations were
      measured using standard assays, and urine pi-GST and alpha-GST enzyme
      measurements were performed by a commercial immunoassay (Biotrin, Biotrin
      International Ltd., Co., Dublin, Ireland). MEASUREMENTS AND MAIN RESULTS: Five
      patients (63%) showed a postoperative elevation of serum creatinine (median
      increase from baseline, 35.4%; range, 8.3% to 50.6%) that was associated with
      significant elevations of urinary microalbumin-to-creatinine, alpha-GST-to
      creatinine, and pi-GST-to-creatinine ratios soon after clamp removal. The
      remaining 3 patients showed no increase in serum creatinine or urine proteins.
      Peak alpha-GST-to-creatinine levels were different between the 2 groups. The peak
      levels of GST enzymes were significantly (r(2) > 80%) associated with the percent
      increase in serum creatinine from baseline. CONCLUSION: Urinary GST-to-creatinine
      ratios are a sensitive early biomarker for renal injury after infrarenal
      abdominal aortic aneurysm repair.

PMID- 12073200
TI  - Does the reimbursement of anesthesiologists for intraoperative transesophageal
      echocardiography promote increased utilization?
AB  - OBJECTIVE: To determine whether access to reimbursement increases
      anesthesiologists' use of intraoperative transesophageal echocardiography (TEE).
      DESIGN: Survey. SETTING: United States. PARTICIPANTS: Members of the Society of
      Cardiovascular Anesthesiologists, local Medicare carriers. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: In year 2000, local Medicare carrier policies
      specifically allowed some form of reimbursement to the attending anesthesiologist
      for intraoperative TEE in 15 states, but barred all forms of reimbursement in 16
      states and Puerto Rico. Data regarding utilization and billing were available for
      702 members of the Society of Cardiovascular Anesthesiologists from these
      jurisdictions who used TEE in their anesthetic practice. Billing patterns were
      found to vary significantly according to the local Medicare policy in effect (p =
      0.004). Use of intraoperative TEE was found to be unrelated, however, to the
      reimbursement available from Medicare (p = 0.2 to 0.7). CONCLUSION: The use of
      intraoperative TEE by anesthesiologists does not seem to be related to the
      availability of reimbursement from Medicare.

PMID- 12073199
TI  - Diltiazem infusion for renal protection in cardiac surgical patients with
      preexisting renal dysfunction.
AB  - OBJECTIVE: To evaluate if the calcium channel blocker diltiazem protects
      postoperatively renal function in cardiac surgical patients with preexisting mild
      to-moderate renal dysfunction. DESIGN: Prospective, randomized, placebo
      controlled, double-blind, clinical study. SETTING: Cardiothoracic anesthesia
      department at a university hospital. PARTICIPANTS: Adult patients undergoing
      elective cardiac surgery using cardiopulmonary bypass, with a preoperatively
      elevated serum creatinine level (n = 24). INTERVENTIONS: Randomized infusions of
      diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7
      microg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes
      before induction of anesthesia and continued for 24 hours. MEASUREMENTS AND MAIN
      RESULTS: Median plasma concentrations of diltiazem (DTZ group) were 79 microg/L
      before cardiopulmonary bypass, 67 microg/L at the end of cardiopulmonary bypass,
      and 164 microg/L at 24 hours postoperatively. Serum creatinine levels; on
      postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between
      groups. Iohexol clearance did not differ between the groups on day 5 but was
      higher in the DTZ group than in the placebo group 3 weeks after surgery (median,
      51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-beta-glucosamidase
      concentrations were similar between the groups during the study but were
      increased from baseline on days 2 and 4 and 3 weeks postoperatively. CONCLUSION:
      Diltiazem can be safely used in patients who have mild-to-moderate renal
      dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the
      limits of this study, the data suggest that addition of prophylactic diltiazem
      may prevent further glomerular damage resulting from cardiopulmonary bypass and
      may improve glomerular function 3 weeks after cardiac surgery.

PMID- 12073201
TI  - The effect of hypothermia on calculated values using saline and automated air
      tonometry.
AB  - OBJECTIVE: To quantify in vitro the effect of hypothermia on results obtained
      when performing automated air tonometry (Tonocap, Datex-Ohmeda, Instrumentarium
      Corp, Helsinki, Finland) and saline tonometry. DESIGN: In vitro validation study.
      SETTING: University hospital research laboratory. INTERVENTIONS: Two TRIP sigmoid
      catheters, one connected to the Tonocap device and the other instilled with 2.5
      mL of 0.9% saline, were placed in a saline bath at 30.3 degrees C (mean) through
      which 5% carbon dioxide (CO(2)) was bubbled. MEASUREMENTS AND MAIN RESULTS: A
      total of 50 paired measurements were taken at 30-minute equilibration times of
      saline bath CO(2) tension and saline tonometry and air tonometry readings. Saline
      samples were analyzed at 37 degrees C and corrected for temperature. Bias and
      precision of each technique as a percentage of predicted CO(2) values were
      calculated. The Tonocap device had bias and precision values of -2.6% and +/
      1.4%. Measurement of CO(2) is in the gaseous phase so that temperature correction
      is not required. Saline tonometry readings processed at 37 degrees C exhibited a
      large positive bias of 23.06% (precision +/- 7.02%). Correction for temperature
      improved bias to -10.98 % with a similar precision profile of +/-5.78%.
      CONCLUSION: When using gastrointestinal tonometry during hypothermic
      cardiopulmonary bypass, saline tonometry samples should be temperature corrected.
      The Tonocap device proved the most accurate and precise measurement technique
      independent of the need for temperature correction.

PMID- 12073202
TI  - Splanchnic blood flow and oxygen uptake during cardiopulmonary bypass.
AB  - OBJECTIVE: To measure splanchnic blood flow (SBF) with 2 indicator dilution
      techniques during and after cardiopulmonary bypass (CPB), to compare the results
      with transesophageal echocardiography Doppler-measured right hepatic vein (RHV)
      flow, and to study gastric tonometry data in the same patients. DESIGN: Single
      arm prospective study. SETTING: University hospital operating room and intensive
      care unit. PARTICIPANTS: Ten adult patients undergoing cardiac surgery.
      INTERVENTIONS: SBF was measured using constant rate infusion of indocyanine green
      dye and low-dose ethanol from induction of anesthesia until end of hypothermic
      CPB. The infusion of ethanol was continued, and SBF was measured postoperatively
      at 2, 3, and 4 hours after CPB. Simultaneously, RHV flow, splanchnic oxygen
      delivery and uptake, and gastric mucosal pH were calculated. MEASUREMENTS AND
      MAIN RESULTS: SBF, RHV flow, and gastric mucosal pH remained unchanged during the
      study period. SBF measured with indocyanine green was 765 +/- 88 (SEM) mL/min
      after induction of anesthesia. SBF before CPB measured with ethanol was 985 +/-
      218 mL/min. There was no significant difference between the methods. RHV flow was
      450 +/- 87 mL/min after induction of anesthesia. There was no correlation between
      individual values of RHV flow and SBF. Splanchnic oxygen uptake was 52 +/- 7.8
      mL/min after induction of anesthesia and decreased to 28 +/- 2.6 mL/min during
      CPB. Gastric mucosal pH was 7.32 +/- 0.02 after induction of anesthesia and
      showed no correlation to SBF or to splanchnic oxygen uptake. CONCLUSION: SBF did
      not decrease during CPB. SBF could be measured with ethanol with reasonable
      accuracy. Transesophageal echocardiography assessment of RHV flow was not
      suitable to quantify SBF in the individual patient, but could be used to follow
      relative changes.

PMID- 12073203
TI  - The antithrombin III-saving effect of reduced systemic heparinization and heparin
      coated circuits.
AB  - OBJECTIVE: To investigate the perioperative changes of antithrombin III (AT-III)
      activity using reduced systemic heparinization and the possible role of AT-III in
      determining a better postoperative outcome. DESIGN: Prospective randomized study.
      SETTING: University hospital. PARTICIPANTS: Patients undergoing elective coronary
      revascularization with cardiopulmonary bypass (n = 90). INTERVENTIONS: Of
      patients, 30 were treated with heparin-coated circuits and reduced systemic
      heparinization; 30, with heparin-coated circuits and full systemic
      heparinization; 30, with conventional circuits and full systemic heparinization.
      MEASUREMENTS AND MAIN RESULTS: Heparin-coated circuits with full systemic
      heparinization did not exert any effect on coagulation parameters. Low systemic
      heparinization resulted in a significantly (p < 0.01) higher hematocrit value on
      arrival in the intensive care unit and in significantly higher values of AT-III
      activity during cardiopulmonary bypass (66 +/- 12% v 57.4 +/- 13% and 59.1 +/-
      12% in the full systemic heparinization groups; p < 0.05), on arrival in the
      intensive care unit (69.7 +/- 13% v 60.7 +/- 13% and 60.8 +/- 11% in the full
      systemic heparinization groups; p < 0.01), and on the first postoperative day
      (81.3 +/- 15% v 67.4 +/- 13% and 70.2 +/- 12% in the full systemic heparinization
      groups; p < 0.01). No differences were observed in the clinical outcome.
      CONCLUSION: Reducing systemic heparinization determines an AT-III-saving effect
      that could be responsible for the decrease in thromboembolic complications
      already observed by other authors. It induces higher hematocrit levels
      immediately after the operation, probably reducing the unmeasurable
      intraoperative blood loss.

PMID- 12073204
TI  - Platelet pheresis is not a useful adjunct to blood-sparing strategies in cardiac
      surgery.
AB  - OBJECTIVE: To examine whether specific platelet pheresis (minimal plasma
      harvested) would contribute toward reduced blood loss and allogenic blood
      requirements after cardiac surgery. DESIGN: A prospective randomized trial.
      SETTING: A large cardiothoracic surgical center. PARTICIPANTS: Consenting
      patients undergoing routine coronary artery or valve surgery (n = 54).
      INTERVENTIONS: Patients in the pheresis group underwent platelet pheresis in the
      anesthetic preparation room before general anesthesia. Pheresed platelets were
      stored during cardiopulmonary bypass and were returned to the patients after
      reversal of heparin with protamine toward the end of surgery. Control patients
      underwent their operations without this intervention. MEASUREMENTS AND MAIN
      RESULTS: Primary endpoints were blood loss and transfusion requirements. There
      were no differences between the 2 groups (pheresis v control: median loss, 960 mL
      v 1100 mL, p = 0.15; median blood transfused, 896 mL v 635 mL, p = 0.71).
      Secondary endpoints included analysis of platelet counts, platelet function, and
      surface markers. Counts remained the same after retransfusion of platelets up to
      2 hours after surgery. Platelet aggregation to ristocetin was well preserved, but
      adenosine diphosphate caused almost no aggregation of the harvested platelets.
      Flow cytometry revealed the platelets to have a reduced surface density of the
      glycoprotein 1b receptor, and 13% of them were irreversibly activated.
      CONCLUSION: Platelet pheresis activates a proportion of the harvested platelets
      and impairs the function of the remainder; this may explain its failure to reduce
      postoperative blood loss and transfusion requirements.

PMID- 12073205
TI  - Does normoxemic cardiopulmonary bypass prevent myocardial reoxygenation injury in
      cyanotic children?
AB  - OBJECTIVE: To evaluate whether the deleterious effect of cardiopulmonary bypass
      (CPB) can be prevented by controlling PaO(2) in cyanotic children. DESIGN:
      Prospective, randomized, clinical study. SETTING: Single university hospital.
      PARTICIPANTS: Pediatric patients undergoing cardiac surgery for repair of
      congenital heart disease (n = 24). INTERVENTIONS: Patients were randomly
      allocated into 3 groups. Patients in the acyanotic group (group I, n = 10) had
      CPB initiated at a fraction of inspired oxygen (F(I)O(2)) of 1.0 (PO(2), 300 to
      350 mmHg). Cyanotic patients were subdivided as follows: Group II (n = 7) had CPB
      initiated at an F(I)O(2) of 1.0, and group III (n = 7) had CPB initiated at an
      F(I)O(2) of 0.21 (PO(2), 90 to 110 mmHg). A biopsy specimen of right atrial
      tissue was removed during venous cannulation, and another sample was removed
      after CPB before aortic cross-clamping. The tissue was incubated in 4 mmol/L of t
      butylhydroperoxide, and the malondialdehyde (MDA) level was measured to determine
      the antioxidant reserve capacity. Blood samples for cytokine levels, tumor
      necrosis factor (TNF)-alpha, and interleukin (IL)-6 response to CPB were
      collected after induction of anesthesia and at the end of CPB before protamine
      administration. MEASUREMENTS AND MAIN RESULTS: After initiation of CPB, MDA level
      rose markedly in the cyanotic groups compared with the acyanotic group (210 +/-
      118% v 52 +/- 34%, p < 0.05), which indicated the depletion of antioxidants.
      After initiation of CPB, TNF-alpha and IL-6 levels of the cyanotic groups were
      higher than for the acyanotic group (168 +/- 77 v 85 +/- 57, p < 0.001; 249 +/-
      131 v 52 +/- 40; p < 0.001). When a comparison between the cyanotic groups was
      performed, group II (initiating CPB at an F(I)O(2) of 1.0) had significantly
      increased MDA production compared with group III (initiating CPB at an F(I)O(2)
      of 0.21) (302 +/- 134% v 133 +/- 74%, p < 0.05). Group II had higher TNF-alpha
      and IL-6 levels than group III (204 +/- 81 v 131 +/- 52, p < 0.001; 308 +/- 147 v
      191 +/- 81, p < 0.01). CONCLUSION: Conventional clinical methods of initiating
      CPB at a hyperoxemic PO(2) may increase the possibility of myocardial
      reoxygenation injury in cyanotic children. This deleterious effect of
      reoxygenation can be modified by initiating CPB at a lower level of oxygen
      concentration. Subsequent long-term studies are needed to determine the best
      method of decreasing the oxygen concentration of the CPB circuit.

PMID- 12073207
TI  - A patient with intracardiac masses and an undiagnosed pheochromocytoma.

PMID- 12073206
TI  - Lithium dilution cardiac output measurement in oleic acid-induced pulmonary
      edema.
AB  - OBJECTIVE: To determine whether lung injury influences the accuracy of lithium
      dilution cardiac output (CO) measurement. DESIGN: Animal experimental study.
      SETTING: Animal experimental laboratory. PARTICIPANTS: Swine (n = 23) weighing
      26.4 +/- 2.47 kg (mean +/- SD). INTERVENTIONS: The animals were anesthetized and
      tracheotomized, then a pulmonary artery catheter was inserted into the right
      jugular vein, and a catheter (18G) was placed in the femoral artery. After median
      sternotomy and pericardiotomy, a left ventricular catheter (18G) was directly
      inserted. CO was measured by giving a bolus injection of lithium chloride into
      either the right atrium or the left ventricle in each animal. After control
      measurements, permeability pulmonary edema was initiated by infusing oleic acid
      into the central vein (injury). About 2 hours after oleic acid infusion, CO
      measurements were repeated in the same manner as the control measurement had been
      taken. MEASUREMENTS AND MAIN RESULTS: Under each condition, right atrium lithium
      injection was similar to left ventricle lithium injection. The mean of these
      differences at injury (-0.06 +/- 0.55 L/min) was the same as that at control (
      0.05 +/- 0.36 L/min). CONCLUSIONS: Although the variability of lithium dilution
      CO measurement after oleic acid-induced pulmonary edema was greater than that of
      the control, this technique was acceptable even in cases of lung injury.

PMID- 12073208
TI  - Excision of adrenal pheochromocytoma and coronary artery bypass graft surgery
      with cardiopulmonary bypass.

PMID- 12073209
TI  - Management of a liver transplant in a patient with asymptomatic superior vena
      cava obstruction.

PMID- 12073210
TI  - An unusual cause of intraoperative confusion in the electrophysiology laboratory.

PMID- 12073211
TI  - Unsuspected Wolff-Parkinson-White syndrome causing arrhythmias after cardiac
      surgery.

PMID- 12073212
TI  - Arrhythmogenic right ventricular dysplasia: an underestimated cause of
      perioperative death?

PMID- 12073213
TI  - Perioperative management of pheochromocytoma.

PMID- 12073214
TI  - Case 3--2002. Pheochromocytoma presenting as a right intra-atrial mass.

PMID- 12073215
TI  - Pro: regional anesthesia is an important component of the anesthetic technique
      for pediatric patients undergoing cardiac surgical procedures.

PMID- 12073216
TI  - Con: regional anesthesia is not an important component of the anesthetic
      technique for pediatric patients undergoing cardiac surgical procedures.

PMID- 12073217
TI  - An unexpected intraoperative finding.

PMID- 12073218
TI  - Unexpected transesophageal echocardiographic finding after septal myectomy.

PMID- 12073219
TI  - Acute pulmonary edema complicating percutaneous balloon valvuloplasty for
      pulmonic stenosis.

PMID- 12073220
TI  - Antifibrinolytic therapy during OPCAB surgery: a word of caution.

PMID- 12073221
TI  - Cell saver for blood conservation in cardiac surgery.

PMID- 12073223
TI  - Transurethral microwave thermotherapy for benign prostatic hyperplasia-
      experience with the Prostcare.
AB  - Transurethral microwave thermotherapy for benign prostatic hyperplasia with the
      Prostcare has been used in our department since April 1992. Our research has
      mainly been focused on strategies for development of the apparatus, accessories,
      and treatment performance to find an optimal means of treatment. The development
      to high-power thermotherapy has demonstrated a significant improvement in symptom
      and quality-of-life scores, maximal flow rate, and residual and voided urinary
      volume after 6 months. Pressure-flow data have additionally demonstrated a
      significant decrease in the minimal urethral opening pressure. The improvement in
      outcome after high-power thermotherapy is associated with an increased short-term
      morbidity as compared with low-power treatment. The outcome is dependent on
      several factors: power and intraprostatic temperatures, treatment performance
      technique, configuration of heat distribution of the antennae, and the
      localization of maximal heat in the prostatic urethra.

PMID- 12073224
TI  - Transurethral microwave thermotherapy for treatment of benign prostatic
      hyperplasia: results obtained with the Prostalund device.
AB  - The 6-month results of treatment with transurethral microwave thermotherapy
      (Prostalund) of 28 patients with lower urinary tract symptoms (LUTS) due to
      benign hyperplasia of the prostate are reported. The median International
      Prostate Symptom Score (I-PSS) fell from 16.5 (range 9-33) to 10.5 (range 3-30; P
      < 0.00005). Quality-of-life assessment improved from a median value of 4 (range 2
      6) to 2 (range 1-5; P = 0.0001). In the Danish Prostate Symptom Score (DAN-PSS)
      the median total score fell from 20 (range 5-55) to 5 (range 0-43; P = 0.001).
      The median peak urinary flow increased from 10.6 to 11.5 ml/s (P = 0.20).
      Pressure-flow studies revealed no decrease in the median detrusor pressure at
      peak uroflow (PdetQmax) from 56 cmH2O preoperatively to 56 cmH2O after 6 months
      (P = 0.36). No change was found in postvoid residual urinary volume or in the
      calculated prostate volume. Complications included hematuria in most patients,
      urinary tract infections in 6 (21.4%) patients, and transient retention in 3
      (10.7%) patients. In all, 20 (71.4%) patients responded to treatment with good
      symptomatic relief, but only minor changes were observed in urodynamic
      parameters.

PMID- 12073225
TI  - Temporary urethral stenting after high-energy transurethral microwave
      thermotherapy of the prostate.
AB  - The objective of this study was to assess the use of temporary stenting of the
      prostatic urethra for the prevention of acute urinary retention after high-energy
      transurethral microwave thermotherapy (TUMT) of the prostate. Stenting was
      performed immediately after high-energy microwave therapy. Two stents were used
      at two sites; at one site a silicone transurethral prostatic bridge was used in
      42 patients, and at the second site a self-reinforced polyglycolic acid (SR-PGA)
      biodegradable spiral was used in 16 patients. Patients were scheduled for TUMT
      for symptomatic benign prostatic hyperplasia. Preoperative investigations
      included determination of a symptom score, measurement of the peak flow rate, and
      determination of the voided volume. The patients were treated using the
      Prostatron TUMT system. The software used provided a maximal power output of 70
      W. After 1 week as well as 1, 3, 6, and 12 months the measurements were repeated
      and the effect of the stents was assessed. The symptom score, peak flow rate, and
      voided volume showed a significant improvement. Improvement was observed at first
      visit and sustained during the follow-up. Prophylaxis of acute urinary retention
      after TUMT can easily be managed by temporary stenting of the prostatic urethra.
      Temporary stenting can be routinely proposed after high-energy TUMT of the
      prostate.

PMID- 12073226
TI  - Case selection for high-energy transurethral microwave thermotherapy.
AB  - Transurethral microwave thermotherapy (TUMT) is a minimally invasive outpatient
      procedure for the treatment of benign prostatic hyperplasia (BPH). Different
      devices and operating software have been used in various clinical trials. The
      objective of this study was to identify the possible baseline parameters that
      could be used to identify the best responders to different microwave devices and
      treatment programs. Data on three different high-energy thermotherapy devices
      (Urowave, Prostalund, and Prostatron) were collected and analyzed. At 1 year of
      follow-up, 166 patients were available for the Prostatron system. In all, 52 had
      a > or = 50% change in both symptom score and peak flow rate, whereas 114
      patients were considered nonresponders. Responders were characterized at baseline
      by a lower peak flow rate (8.80 versus 10.48 ml/s, P < or = 0.0001) and a larger
      degree of outlet obstruction as measured by the URA parameter (45.33 versus 36.70
      cmH2O, P < or = 0.0300); a larger energy dose was delivered to this group during
      treatment (173.36 versus 156.40 kJ, P < or = 0.0258). A total of 19 patients were
      available from the Prostalund cohort. No significant difference was found in the
      values recorded for baseline parameters between responders (5 patients) and
      nonresponders (14 patients). Stratification of 143 patients treated with the
      Urowave resulted in 29 responders (> or = 50% improvement in both Qmax and AUA
      score) at 6 months of follow-up, with a significant difference being found in the
      baseline value recorded for peak flow rate (7.0 versus 8.0 ml/s, P < or = 0.026).
      At 12 months, however, this significance difference could no longer be found. In
      conclusion, baseline parameters with significant predictive value for a clinical
      response could be identified for the Prostatron device only. The results of this
      study further confirm the importance of an extensive laboratory and clinical
      research program for a fuller understanding of the clinical response obtained
      with a certain microwave device and a particular treatment software and for
      provision of the greatest possible advantage from these new alternative
      treatments. Further exploratory work is required for a better understanding of
      the role of other parameters such as prostate tissue architecture and
      vascularity, the microwave frequency, the applicator design, the intraprostatic
      temperature, and the treatment duration in the clinical response to microwave
      thermotherapy.

PMID- 12073227
TI  - Urodynamics and transurethral microwave thermotherapy.
AB  - In this paper the role and value of urodynamic measurements in symptomatic benign
      prostatic hyperplasia (BPH) patients selected for transurethral microwave
      thermotherapy (TUMT) reviewed. Although pressure-flow studies alone can diagnose
      benign prostatic obstruction, the level of acceptance of urodynamic
      investigations in BPH remains low, reportedly due to their cost and to their
      invasive and time-consuming nature. Furthermore, the observation that extremely
      different treatment modalities in BPH have nearly the same symptomatic outcome,
      independently of their influence on obstruction, has played a part in raising
      doubt as to the value of baseline urodynamics as a predictor of clinical success.
      Pre- and posttherapy urodynamic investigations in TUMT-treated patients have
      shown that urodynamic algorithms must be capable of distinguishing between
      compressive and constrictive types of obstruction to document the limited effects
      of low-energy TUMT on obstruction. Furthermore, it has been shown that
      urodynamics evaluated in this way seems to be the only predictor of the clinical
      success of TUMT when improvements in the objective parameters Qmax (peak uroflow)
      and residual urine are included in the definition of outcome.

PMID- 12073228
TI  - Economics of transurethral thermotherapy of the prostate.
AB  - Costs of BPH management is increasing dramatically and may represent as much as
      1% of total National Health Service expenditure. It is important to offer the
      patients effective treatment and to offer the society cost-effective treatment.
      The ideal cost-effectiveness or cost-utility analysis includes not only
      evaluation of outcome but also socioeconomic and intangible costs ("quality of
      life" costs). Studies on economics of the newer less invasive treatment
      modalities for BPH such as transurethral microwave thermotherapy of the prostate
      (TUMT) are scarce. Parameters important in the consideration of economy in TUMT
      are capital and disposable costs, retreatment rate and discount percentage. More
      studies are needed to make precise cost estimations for TUMT, but at present,
      TUMT seems comparable to TURP in cost-effectiveness.

PMID- 12073229
TI  - The economic impact of introducing transurethral microwave thermotherapy in the
      treatment of benign prostatic hyperplasia: a scenario analysis.
AB  - The goal of this study was to assess the economic impact of introducing
      transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic
      hyperplasia (BPH). Different scenarios were constructed using both randomized
      clinical trial data and observational data on resource use related to BPH
      treatments. These include a baseline scenario, demand scenarios reflecting the
      number of men who will be treated by TUMT when it is introduced, and supply
      scenarios reflecting the number of hospitals that will provide TUMT. In the
      baseline scenario, costs of BPH treatment equal Netherlands guilders (NLG) 203
      million. If the demand for BPH treatment does not increase following the adoption
      of TUMT, costs may vary between NLG 187 and 189 million, depending on how TUMT is
      provided. If the demand increases up to 25% following the introduction of TUMT,
      costs may vary between NLG 457 and 466 million, depending on how TUMT is
      provided. The introduction of TUMT seems to be cost-saving, but savings depend on
      the number of men who seek treatment for BPH. There is no indication for a
      controlled provision.

PMID- 12073230
TI  - Quality-of-life assessment in patients treated with lower-energy thermotherapy:
      Prostasoft 2.0.
AB  - This study was designed to evaluate the impact of lower-energy transurethral
      microwave thermotherapy (TUMT) on quality of life (QoL) and quality of sexual
      function (QSF) in patients with benign prostatic hyperplasia (BPH). A total of
      216 patients with BPH received lower-energy TUMT treatment (Prostasoft 2.0) and
      were followed until 1 year after treatment. All patients completed a Madsen
      symptom score and QoL questionnaire to assess their perception of urinary
      difficulties, sexual functions, activities of daily living, psychological well
      being, and social activities. The maximal uroflow changed from 7.8 ml/s at
      baseline to 11.2 ml/s after 1 year. The Madsen symptom score improved from 14.0
      to 5.7. With regard to QoL, we saw a significant improvement in the perception of
      urinary difficulties and activities of daily living. No statistically significant
      improvement in QoL measures documenting sexual functions, psychological well
      being or social well-being was observed. Besides a significant improvement in
      objective and subjective clinical parameters, we also observed an improvement in
      QoL. In addition to the minimally invasive character of this therapy, also the
      preservation of sexual functions is very appealing.

PMID- 12073231
TI  - Future aspects of TUMT treatment of benign prostatic hypertrophy.

PMID- 12073232
TI  - Recent strategies for the use of paclitaxel in the treatment of urological
      malignancies.
AB  - Paclitaxel, a natural anticancer drug, has gained widespread acceptance as an
      active broad-spectrum antitumor agent, including its use in urological
      malignancies, particularly urothelial tract cancer and testicular cancer. The
      mechanism of action, based on the premature stabilization of the microtubule
      assembly with disruption of the cytoskeletal framework, is completely different
      from those of DNA-damaging agents, e.g., cisplatin and ifosfamide. As a single
      agent, paclitaxel is one of the most active drugs in metastatic bladder cancer,
      with an overall response rate of 40-50% being obtained in previously untreated
      patients. These promising single-agent results have prompted the use of
      combination regimens including, in particular, cisplatin and paclitaxel. A high
      degree of activity for the cisplatin-paclitaxel combination as reflected by
      responses in 50-80% of patients, including a substantial number of complete
      responses (> 30%), has been identified. The role of other agents such as
      vinorelbine, methotrexate, 5-fluorouracil, or ifosfamide as additions to this two
      drug combination currently remains open. The combination of paclitaxel plus
      ifosfamide or vinorelbine in the absence of a platinum derivative has yielded
      rather disappointing results. Of particular interest may be the combination of
      paclitaxel and carboplatin. Both drugs can be given to patients with impaired
      renal function. Overall response rates of 45-60% have been reported in phase II
      studies. The so-called platelet-sparing effect of paclitaxel given in combination
      with carboplatin has resulted in a surprisingly low frequency of myelotoxicity,
      particularly thrombocytopenia. The combination of paclitaxel with carboplatin is
      being compared in an ongoing trial against the current standard MVAC regimen
      (methotrexate/vinblastine/Adriamycin/cisplatin) in patients with metastatic
      disease. Furthermore, the activity of paclitaxel-based combinations is currently
      being explored in the neoadjuvant setting in phase II studies, and the potential
      for the combination with the other new promising agent--gemcitabine--will be
      evaluated in a phase I setting. In prostate cancer, estramustine phosphate is
      widely used as palliative treatment for patients with hormone-refractory disease.
      In vitro synergistic activity has been observed between estramustine and
      paclitaxel in prostate-cancer cell lines, although paclitaxel has not
      demonstrated single-agent activity in patients with hormone-refractory prostate
      cancer. In clinical trials the combination of the two agents was associated with
      increased gastrointestinal toxicity. The addition of etoposide as a third drug
      has yielded prostate-specific antigen (PSA)-response rates of > 50%, but data on
      quality of life and survival time have not been reported for these combinations.
      A true clinical role for paclitaxel in prostate cancer has therefore not been
      established. Paclitaxel has finally demonstrated single-agent activity in
      relapsed and/or cisplatin-refractory testicular cancer in recent phase II trials,
      indicating different mechanisms of resistance to cisplatin and paclitaxel. These
      results have formed the rationale for the introduction of paclitaxel as part of
      combination chemotherapy regimens in patients with relapsed but chemosensitive
      testicular cancer. Preliminary results demonstrate that paclitaxel can be safely
      included into these conventional-dose combination regimens. When it is used prior
      to high-dose chemotherapy, sufficient numbers of peripheral blood stem cells
      (PBSCs) for high-dose therapy can be collected. The final role of paclitaxel in
      risk-adapted chemotherapeutic strategies in testicular cancer is not defined, but
      it appears that paclitaxel-based combinations can achieve a substantial response
      rate in patients with relapsed disease.

PMID- 12073233
TI  - Transurethral microwave thermotherapy in BPH.

PMID- 12073234
TI  - Mechanism of microwave thermotherapy.
AB  - Possible mechanisms by which transurethral microwave thermotherapy creates an
      improvement in vodiing parameters are reviewed. The therapy creates coagulation
      necrosis in the hyperplastic adenoma, and thus has the potential to create volume
      reduction, change in the periurethral tissue, and changes in efferent
      neuromuscular elements and sensory neural elements. Evidence is presented that
      suggests that several of these mechanisms are likely important, and there is not
      a singular mechanism of action.

PMID- 12073235
TI  - Transurethral thermotherapy using the Prostatron device.
AB  - This paper reviews the available data on low- and high-energy transurethral
      microwave thermotherapy (TUMT) in the treatment of patients with benign prostatic
      hyperplasia (BPH). Furthermore, it provides a perspective for this minimally
      invasive treatment modality in the selection of patients and in future
      developments. In evaluations of the two software modalities, several clinical
      studies have proved them to be effective. Whereas the lower-energy software seems
      to be the better choice for treatment of patients with lower urinary tract
      symptoms who have a lower grade of outlet obstruction and a smaller prostate, the
      higher-energy mode should be used to deobstruct and can be used in patients with
      larger prostates and moderate to severe outlet obstruction. Although baseline
      parameters can be used to predict the response to treatment in the higher-energy
      software mode, the total amount of energy remains very important for the final
      outcome, and future efforts should be encouraged to quantify prostate
      vascularization and histology in relation to transurethral microwave heating.
      Furthermore, future developments should focus on shorter treatment times and
      minimization of morbidity.

PMID- 12073236
TI  - Transurethral microwave thermotherapy in the treatment of benign prostatic
      hyperplasia: results obtained with the Urologix T3 device.
AB  - The objective of this study was to assess the efficacy and safety of a new
      transurethral microwave thermotherapy device, T3, in the treatment of symptomatic
      benign prostatic hyperplasia. A total of 155 patients were recruited at 3 sites
      and treated using an identical protocol. The mean AUA symptom score decreased by
      58% at 12 months, by 61% at 24 months and by 56% at 36 months. The increase in
      mean peak flow rates at these time points was 3.9 (47%), 3.4 (44%) and 5.1 ml/s
      (67%), respectively. Adverse events were minor and the patients' satisfaction
      with treatment was high. Transurethral microwave thermotherapy with the T3 device
      provides a safe, effective treatment for symptomatic benign prostatic
      hyperplasia.

PMID- 12073237
TI  - [Effect of atenolol combined with chlortalidone on characteristics of 24-hour
      blood pressure monitoring].
AB  - Data are submitted concerning effects of atenol-H on indices for 24-hr monitoring
      of arterial pressure. As many as 34 patients were examined presenting with stage
      II hypertensive disease, in whom a 24-hr monitoring of AP was carried out in
      addition to a conventional measurement of AP as recommended by Korotkov before
      and after treatment with atenol-H, 1 tabletta per day (atenolol 100 mg,
      chlortolidon 25 mg). The course of treatment was on the average (26.8 +/- 1 to 4)
      days. As a result of treatment, values for 24-hr, day, and night AP have gotten
      decreased. No serious complications have been revealed to warrant withdrawal of
      the drug.

PMID- 12073238
TI  - [Use of enterol in the treatment of diseases complicated by diarrhea syndrome].
AB  - The article analyses data on clinical efficacy of the drug enterol in patients
      with chronic pancreatitis and chronic atropic gastritis. The use of enterol in a
      complex therapy has been shown to favour quick dispelling of the pain and
      dyspeptic syndromes, normalization of stools, elimination of intestinal
      dysbacteriosis or alleviation of its gravity.

PMID- 12073239
TI  - [Prospects of use of gene therapy in head trauma].
AB  - Neuronal injury may have one of the following three sequelae: death of the
      neurone, persistent atrophy or recovery. The ability of mature neurones to
      recover is dependent to a not inconsiderable degree on neurotrophins, on the
      basis of which consideration the following objective of genotherapy in
      craniocerebral injury (CCI) is formulated: achievement of therapeutically useful
      levels of expression of neutrophins by employment of genetical methodological
      approaches. The next prerequisite for institution of genotherapy in CCI is a
      proved dependance of CCI sequelae on individual genetic features, on APO E
      genotype in particular, which fact suggests to us that specific correction is
      within the bounds of possibility. Another precondition for use of genotherapy in
      CCI is considered to be higher permeability of the blood-brain barrier in trauma,
      which even can facilitate the delivery of transgenes into the brain with the aid
      of those vectors the access of which to the central nervous system is limited
      under other conditions.

PMID- 12073240
TI  - [Effect of perftoran emulsion ventilation of lungs on the pulmonary surfactant
      system in patients with acute lung injury syndrome].
AB  - The condition was studied of the pulmonary surfactant system in those patients
      with the syndrome of acute lung injury who had been placed on a partial emulsion
      ventilation of the lungs. The study of the surface tension of the endobronchial
      washings was made with the aid of the modified Willihelm balance before the start
      of the treatment and at post-treatment day 4, 6 and 8. The initial level of
      surface tension has been found out to be increased by 8.9%. The controlled
      indices were gradually returning to normal in the wake of the emulsion
      ventilation of the lungs. Partial emulsion ventilation of the lungs with
      perftoran makes for a prompt and complete restoration of surface activity of the
      pulmonary surfactant within 7 days. We consider it essential that a conventional
      intensive therapy of the acute lung injury syndrome be supplemented by partial
      emulsion ventilation of the lungs with perftoran.

PMID- 12073241
TI  - [Therapeutic efficacy of lacidipine in patients with chronic glomerulonephritis
      and diabetic nephropathy].
AB  - A total of 30 patients with diabetic nephropathy were examined together with 30
      patients presenting with chronic glomerulonephritis at different stages of the
      condition. An unquestionable positive effect has been demonstrated of lacidipine
      on the arterial pressure, glomerular filtration rate, proteinuria, diuresis,
      excretion of nitrogenous metabolities in patients with the above pathology
      presenting with the normal or impaired renal function. A prognostic criterion has
      been developed for efficiency of treatment with lacidipine making use of the
      corinfar test.

PMID- 12073243
TI  - [Characteristics of measles epidemics in the Donetsk region population under
      conditions of regular immunization].
AB  - With vaccination having become usual practice in health care, the incidence rate
      of measles in the Donetsk region has fallen 53.6-fold versus the prevaccination
      period. Bet there are also negative processes in the epidemiology of measles; of
      these, ever more frequent occurrence of the infection under consideration in
      persons of mature years is worthy of particular mention. The specific weight of
      juveniles and grown ups had come to be 68.65% in 1998 vs 6.3% in 1975. Since 1993
      the case rate of measles is noted to be at its greatest among children less than
      two years of age and among adolescents, which fact can be referred to effects on
      the level of immunity of different factors including that of time of more than
      five years having elapsed since the previous immunization. The administration in
      1997-1998 of vaccines to non-vaccinated persons and to unprotected ones permitted
      the incidence rate of measles to be kept down in juveniles and adults but the age
      brackets of sick persons were in fact the same as before the additional
      vaccinations done. The state of things discribed above attests to the need for
      development of cardinal measures to raise the level of individual and collective
      immunity in juveniles and adults.

PMID- 12073242
TI  - [Hentaxan as an immunoregulator in purulent wounds in parturient women].
AB  - Hentaxan, a new silicon sorbent, is a complex drug preparation containing
      hentamycin sulfate and zinc-tryptophan, endowed with antioxidant and
      immunomodulating activities. We used it for treating suppurating wounds in those
      women in labour. As many as 65 parturient women were examined. The conclusion
      drawn from the obtained results is that the immunomodulating potential of
      hentaxan is not very high, for which reason we recommend that hentaxan be
      combined with laferon which effects the T-link of immunity. The proposed method
      is at present under study.

PMID- 12073244
TI  - [Role of family practice in prevention of ischemic heart disease].
AB  - Family medicine as a system of primary medical care delivery to man and his
      family can become under conditions of this country a mainstay of a successful
      realization of preventive strategies for chronic noninfectious diseases, and, in
      the first place, for ischemic heart disease. The article presents a project of a
      simplified scheme of actions for a family physician to carry on a prophylactic
      work among the population of his sector community. The stages the above scheme
      involves are as follows: assessment of an individual and general populational
      risk, dividing of the population into main groups of risk, implementation of
      measures designed to carry on a program of intervention intended for each group
      of the population with special reference to individual traits.

PMID- 12073245
TI  - [Organization of outpatient medical care delivery in a Kiev garrison].
AB  - The article addresses the issue of organization of the medical care delivery to
      servicemen of the Kiev garrison. Substantiated in the paper is the organizational
      and-staff structure of the clinic of the Chief Military Clinical Hospital of the
      Ministry of Health of Ukraine. Results of work carried on within the framework of
      home care programs are highlighted.

PMID- 12073246
TI  - [Health status and fitness of the young men for military service].
AB  - Submitted in the article are medical causes of unfitness of those men called up
      for military service in peace-time. These include psychic dysfunctions (22%),
      traumata (18.5%), disorders of the nervous system and sensory organs (14.5%), of
      the osteomuscular system and connective tissue (13.3%), digestive diseases
      (8.6%). Mental disorders, those of the nervous system and sensory organs, the
      endocrine system and digestive organs rank first among causes of striking the
      serviceman off the register, coming up to 40.9%, 31.2%, and 6.8% respectively.
      Age has been established at which disease manifestations causing unfitness for
      military service come to reveal themselves: in 58.4 percent of registrants the
      above manifestations were first diagnosed in childhood, in 5.4 percent--at 16 to
      17 years of age, in 36.2 percent--at call-up age.

PMID- 12073247
TI  - [Medical officers--graduates from the Army Medical Department at the Kubyshev
      Medical Institute (on the 25th anniversary of graduation)].
AB  - The article is devoted to graduates from the army medical faculty with the
      Kuibyshev Medical Institute in 1979. The above faculty graduates service in the
      Armed Forces of Ukraine and at the Defence Ministry of the Republic of Belarus is
      briefly analysed.

PMID- 12073248
TI  - [Endothelin-1 level in the complicated course of myocardial infarction].
AB  - In the uncomplicated course of myocardial infarction (MI), the level of
      endothelin-1 (ET-1) comes to be increased beginning from day 1 and remains the
      same during the acute phase of the disease and gets decreased during the subacute
      phase. In MI presenting with parietal thrombosis, left ventricular aneurism, the
      level of ET-1 increases during the first period of 24 hours, increasing further
      toward the end of the acute phase, there being no decrease in the subacute phase.
      In MI presenting with pericardial effusion, an increase in the level of ET-1 is
      seen during the first period of 24 hours of the disease with no rise being
      recordable in peptide concentration during the acute and subacute phases. There
      is a positive correlation between the level of ET-1 and size of the heart
      cavities in the systole and diastole, pressure in the pulmonary artery, and a
      negative one with indices for the systolic function.

PMID- 12073250
TI  - [Effect of non-steroid anti-inflammatory and glucocorticoid agents on development
      of gastrointestinal lesions in patients with rheumatic diseases].
AB  - A comparative evaluation was done of frequency and severity of upper
      gastrointestinal mucosal lesions in patients taking nonsteroid antiinflammatory
      drugs (NSAID) and glucocorticosteroids (GCS). A total of 65 rheumatic patients
      examined endoscopically entered the study. The patients were divided into three
      groups. Group I comprised 12 patients placed on GCS only, group II was 35
      patients on NSAID, group III was 18 patients who received NSAID plus GCS.
      Gastropathies were diagnosed in 25%, 45.7%, 44.4% of patients in groups I, II,
      and III respectively. Group II patients had a higher incidence of serious
      afflictions. As far as the gastrointestinal mucosa is concerned, GCS have been
      shown to be superior to NSAID. A combined use of NSAID + GCS, unlike NSAID alone,
      has not been found to increase the risk of development of gastropathy.

PMID- 12073249
TI  - [Clinical and hemodynamic characteristics of heart dysfunction in patients with
      iron deficiency anemia].
AB  - Clinical-and-hemodynamic manifestations of heart failure were studied in 28
      patients with iron deficiency anemia (IDA). Half of the IDA patients have been
      found out to develop the heart failure syndrome of both systolic and diastolic
      variant. Decrement in exercise tolerance in the above patients is due to anemia
      as well as to development and progression of the cardiac muscle dysfunction,
      which fact warrants an in-depth diagnostic quest together with an optimum
      treatment.

PMID- 12073251
TI  - [Bacterial infections complicating gastrointestinal diseases in victims of the
      Chernobyl catastrophe].
AB  - Overall 303 patients with digestive diseases who had been exposed to adverse
      factors because of the Chernobyl accident were examined. Of these 124 subjects
      (40.9%) had degree II-III dysbacteriosis of the large intestine that is believed
      to develop in the wake of disordered immunity, cholesecretion, and bilification
      as well as of decline in the enzyme-excretory function of the pancreas.

PMID- 12073252
TI  - [Morphofunctional state of neutrophil granulocytes in Chernobyl nuclear plant
      accident clean-up workers with persistent leukopenia].
AB  - The obtained results of the analysis of the peripherical blood granulocytes
      morphofunctional condition in those persons who took part in the elimination of
      aftermaths of the Chernobyl accident, presenting with persistent leucopenia,
      suggest to us the presence of significant changes in morphological, cytochemical,
      and functional indices in the remote period.

PMID- 12073253
TI  - [Alterations in coronary arteries and frequency of episodes of transient
      myocardial ischemia in patients with ischemic heart disease with typical and
      atypical angina pectoris].
AB  - A total of 169 patients with ischemic heart disease were examined. Group I
      comprised 105 patients with angina pectoris, group II was 64 patients presenting
      with an untypical pain syndrome. A single affection of the coronary artery (CA)
      was more frequently seen in group II subjects (50 percent versus 16.1% in group I
      persons). Affection of three CA was more common in group I subjects (41.1% versus
      30%). Affection of the main stem of the left coronary artery was recordable in
      7.6 percent of subjects in group I and was undetectable in group II patients. It
      has been established that both in single and associated affections of CA,
      affection of the right CA and that of the circumflex branch was significantly
      more common in group II subjects. With affection of two and three CA in persons
      with stenocardia, there was no significant difference between the number of
      algesic and non-algesic episodes of myocardial ischemia (MIE) (44.4 and 55.6% and
      41.6 and 58.3% respectively). In those examinees without typical stenocardia, in
      affection of two CA the algesic MIE comprised 20%, non-algesic--80%; in affection
      of three CA algesic MIE came up to 55.6%, non-algesic--44.4%. In this way, in
      affection of three CA, the number of both algesic and non-algesic MIE in angina
      persons was not significantly different from that in subjects free from angina.

PMID- 12073254
TI  - [Reactions and complications caused by thrombocyte concentrate transfusions].
AB  - The review contains current data on complications developing in the wake of
      employing thrombocytes concentrate in clinical settings. Complication patterns
      are submitted, causes thereof are analyzed. Technical aspects are discussed of
      optimum measures to be implemented in transfusions of the thrombocytes
      concentrate.

PMID- 12073256
TI  - [Assessment of variations in heart rate and in daily monitorings of arterial
      blood pressure in patients with circulatory encephalopathy].
AB  - As many as 93 patients with discirculatory encephalopathy having developed
      against the background of arterial hypertension were examined with the aid of
      Holter arterial pressure and cardiac cycle variability monitoring. Shown in the
      article is an apparent positive effect of laseropuncture and acupuncture versus
      conventional therapies and an expediency of employing Holter monitoring.

PMID- 12073255
TI  - [Chymase in the system proteinase-proteinase inhibitor in pathogenesis of
      hypertension].
AB  - Investigated in the study was activity of proteinases, nontripsin-like
      proteinases (NTLP), a1-inhibitor of proteinases (a1-PI), and a2-macroglobulin (a2
      MG) in the blood serum of workers of the Kharkov tile plant and those of the
      Institute of Therapy of the AMS of Ukraine, who had been exposed to stress
      factors, and during the early stages of hypertensive disease (HD). The activity
      of proteinases, NTLP appeared to be decreased in the group of HD patients. In
      both groups there was a decrease in the level of a1-PI and a rise of the activity
      of chimase, a2-MG. The authors have come to the conclusion about prevailing of
      nervous, immunological stimuli in the above examinees, specificity of the part
      chimase has in formation and progression of HD, and important role that a2-MG
      plays in the activity of chimase.

PMID- 12073257
TI  - [Central and intracardiac hemodynamics in patients with duodenal ulcer and
      Helicobacter infection].
AB  - The study of central hemodynamics, indices for 24-hour ECG monitoring and
      microcirculation in 97 patients with peptic ulcer of the duodenum (DU) (57 men
      and 40 women) who ranged from 21 to 65 years old with regard for the presence of
      H. pylori infection and ischemic heart disease (IHD) permitted coming to the
      conclusion that ingestion of food in DU patients results in perversion of the
      hemodynamic response manifested by drop in the stroke (SI) and cardiac (CI)
      indices. Arresting of signs of exacerbation of the ulcer process is accompanied
      by normalization of the reaction of central hemodynamics to the food ingestion
      presenting as increase in SI and CI. The presence of H. pylori in elderly DU
      patients has been found to contribute to more aggressive course of IHD.

PMID- 12073258
TI  - [A comparative study of efferent methods of treatment and bezonal on the
      absorptive and excretory liver function in patients with acute diffuse
      peritonitis].
AB  - Patients with acute general peritonitis display in the postoperative period
      manifest disturbances in the pharmacokinetics of cardiogreen. Conventional
      therapies, blood ultra-violet irradiation procedures, intravascular irradiation
      of blood with laser, and hyperbaric oxygenation have no positive effect on the
      detected inadequacies. Hemosorption embarked on in the complex of therapeutic
      measures in the above category of patients appeared to have but insignificant
      positive effect. Benzonal has been shown to have an apparent corrective effect on
      disordered pharmacokinetics of cardiogreen in patients with acute general
      peritonitis in the postoperative period.

PMID- 12073259
TI  - [Clinical and pathogenic evaluation of acid-base, gas and electrolyte homeostasis
      in patient with leptospirosis and acute renal insufficiency].
AB  - With the purpose of further perfecting the pathogenetic therapy, indices for the
      acid-base status were studied together with those for the electrolyte exchange in
      the time-related course of the disease in patients with grave leptospiral
      jaundice presenting with acute renal failure (ARF). Patients with leptospirosis
      running a grave course and ARF display changes in the acid-base status and gas
      composition of the blood. Patients presenting with oligoanuric ARF and fatal
      outcome develop uncompensated metabolic acidosis (11.8%), in case of favourable
      outcome--metabolic acidosis with compensation by respiratory alkalosis (29.4%).
      The polyuric ARF stage is characterized by a mixed metabolic and respiratory
      alkalosis (58.8%). Results of studies made warrant use of indices for the acid
      base, gas, and electrolyte balance to assess severity and prognosis of
      leptospirosis, to determine the stage of ARF, and to develop rational
      pathogenetic therapies.

PMID- 12073260
TI  - [Body temperature regulation as a prognostic criterion for the postoperative
      period in patients with femoral fractures].
AB  - Frequency is studied of adequate, redundant, inert, and reduced types of
      thermoreactivity in healthy subjects and patients with fractures. Definition of
      type of thermoreactivity to cooling in patients with fractures of the thighbone
      permits prognosticating the course of the bone fracture healing process. The
      symptom of distal hyperthermia/hypothermia is unspecific but is regarded as a
      supplementary index of the type of thermoreactivity and character of the course
      of the fracture healing process.

PMID- 12073261
TI  - [Prognosis, prophylaxis, and early therapy of fetoplacental insufficiency].
AB  - Parameters characterizing the bloodflow, system of hemostasis, were determined
      together with the level of the key hormones (estriol and placental lactogen) in
      70 pregnant women running a risk for development of placental insufficiency as
      well as in those pregnant women presenting with clinical manifestations of
      placental insufficiency at week 6 to 40. The parameters have been noted to get
      worse during the period of placentation. Augmentation of resistance of the
      uterine arteries and umbilical artery, ultrasonic signs, decline in the hormonal
      activity of the placental complex, changes in the hemostasiogram--all these
      events come to be seen before the appearance of the first clinical signs of
      placental insufficiency. The studied parameters have been shown to get improved
      by early complex treatments of administration.

PMID- 12073262
TI  - [Causes of pre-24 hour mortality in myocardial infarction].
AB  - In spite of achievements of modern cardiology cardiovascular mortality is still
      heavy. The first 24-hour mortality in myocardial infarction (MI) is dependent on
      a timely care delivery at the hospital stage. Causes are studied of pre-24 h
      lethality in 141 MI persons. Recommendations are given on reduction of the level
      of mortality.

PMID- 12073263
TI  - [A treatment modality for children with heart and rheumatic diseases who are
      frequently ill with respiratory infections].
AB  - Our objective in this study was to carry out an immunological assessment of use
      of immunomodulating agents in a complex therapy of those children with poor
      health who are always ailing and present with cardiorheumatological pathology. A
      way for prevention of aggravation of cardiorheumatological pathology is
      submitted, involving the use of bronchomunal and narine according to the
      developed treatment regimen.

PMID- 12073264
TI  - [Treatment of anemia in rheumatoid arthritis with transplantation of hemopoietic
      stem cells from human embryonic liver].
AB  - The article describes chief links of pathogenesis of anemia in rheumatoid
      arthritis (RA). These include the blood hyperviscosity syndrome, abnormalities of
      iron metabolism, blockade of iron in the reticuloendothelial system, hemolysis,
      depression of erythropoiesis. Indices for the hemoglobin peripheral blood,
      erythrocytes, reticulocytes, platelets in the group of RA patients were analysed
      together with their changes under exposure to transplantation of hemopoitic stem
      cells of human embryional liver.

PMID- 12073265
TI  - [Different therapeutic approaches for chronic diffuse liver lesions using
      ornicetil, lactulose, etimizol and corinfar].
AB  - Different therapeutic regimens were tried in 67 patients with hepatic cirrhosis
      and in 54 patients with chronic hepatitis depending on the leading pathological
      syndrome. Treatment schemes involved the use of the drug ornicetil in patients
      having acute episodes of portal systemic encephalopacy, lactulose in those
      presenting with an increased content of ammonia in the blood and symptoms of
      chronic portal systemic encephalopacy; etimizol was given to those patients with
      an apperant antioxidant imbalance. Differentiated approaches to the institution
      of curative measures permitted improving considerably the patients' medical
      rehabilitation, achieving regression of pathological manifestations. It has been
      found out that the above drugs exert a positive effect on the cytolytic and
      mesenchimal-inflammatory syndromes and will, we believe, come to be widely used
      for treating diffuse lesions of the liver.

PMID- 12073266
TI  - [Characteristics of chronic viral hepatitis B in children of various ages].
AB  - A long-term follow-up of children with high degree activity chronic viral
      hepatitis B (CVH B) permitted establishing certain age-associated differences in
      the time-related course of the pathological process. In children aged 1 year, in
      spite of a continuing increase in the size of the liver, the degree of certain
      clinical manifestations of the disease tends to be lower as days pass by, the
      rate being not high. Enlargement of the liver sizes, going on and on, and an
      appreciable degree of meteorism are regarded as a cause of a considerable
      increase in the belly's mass. Rare development of hemorrhagic phenomena is worthy
      of mention. In children 1 year old and in those less than three years of age, in
      spite of instability of a number of clinical manifestations, CVH B runs more
      often than not progredient course and is associated with a relatively favourable
      prognosis. There is an age-related increase in the frequency of the wave-like
      course of the disease, which fact is probably a cause of acceleration of both
      time of formation of hepatic cirrhosis and recovery from the illness. The above
      features of CVH B course in different age groups of children are to be taken
      account of in deciding between treatment alternatives.

PMID- 12073267
TI  - [Therapeutic policy in stage I-II laryngeal cancer].
AB  - Radio-, chemoradiation (with making use of cysplatin and 5-fluorouracil)
      therapies were employed together with a surgical method as treatment of 197
      patients with T1-2N0M0 laryngeal cancer. Efficiency of the methods each was
      assessed by recurrence-free source of the disease, survivals, and by functional
      results as well. The best results in the treatment of T1N0M0 laryngeal cancer
      have been found out to be secured with the use of the surgical method, as
      evidenced by the analysis of the clinical material--94.3 percent of patients are
      free from recurrence and metastases for more than three years versus 81.6 percent
      with the radiotherapy method. In T2N0M0 laryngeal cancer, 70% of patients are
      free from recurrence and metastases after radiotherapy treatments. With
      chemoradiotherapy and surgical treatment these parameters comprised 88.8% and
      11.2%; 91.5% and 8.5%. In T2N0M0 glottic cancer the surgical method is considered
      to be superior to other options.

PMID- 12073268
TI  - [Treatment of patients wtih malignant lymphoma with freeze-dried cord blood].
AB  - It has been ascertained that in patients with malignant lymphomas, employment of
      cryopreserved cells of the cord blood (CB) is associated with a high efficiency
      of therapy of the underlying medical condition. With introduction of CB into the
      test-system of the donor's blood the T-lymphocytes radiosensitivity has been
      shown to be increased during the Go- and S-periods of the cell cycle, which fact
      should be taken account of in planning radiotherapy in oncological patients. A
      decrease in the level of aneuploid lymphocytes against the background of blast
      transformation as a result of transfusion of CB may suggest normalization of the
      pool of lymphocytes.

PMID- 12073269
TI  - [Clinical efficacy and roentgen results of laser therapy in combined treatment of
      patients with newly diagnosed pulmonary tuberculosis].
AB  - Efficiency was studied of use of laseropuncture in a complex treatment of 80
      patients with pulmonary tuberculosis first diagnosed. The results of studies made
      showed that use of laseropuncture in the treatment complex promote significantly
      the dissipation of the intoxicatory and bronchopulmonary syndromes, the bacteria
      no longer recovered, the time of closure of the cavities of decomposition getting
      shortened, the indices for the function of external breathing improved.

PMID- 12073270
TI  - [Neurotic disorders in adolescents with vegetative dysfunction].
AB  - The main disorders in juveniles who are resident in the zone of small doses of
      ionizing radiation are vegetative dysfunctions. Of these, there prevail
      vegetovascular dysfunction comprising 45.7%, with neurocirculatory and
      vegetovisceral dysfunctions occurring less frequently (26.3% and 19.7%
      respectively). The major proportion of juveniles present with neurosis-like
      states, asthenic and asthenodepressive ones being the most common type.

PMID- 12073271
TI  - [Effectiveness of different strategies of vaccine prophylaxis for poliomyelitis
      in the Ukraine].
AB  - The use of oral poliomyelitis vaccine (OPV) in Ukraine permitted achieving
      absence of cases poliomyelitis caused by "wild" polioviruses. All registered in
      recent years cases of poliomyelitis are associated with vaccination. In quest of
      optimal schemes of vaccination the study was made of the immunity tension in
      children with making use of an inactivated poliomyelitis vaccine (IPV). IPV + IPV
      + IPV/IVP + OPV + OPV schemes of immunization are more effective as compared to
      the conventional scheme of immunization (OPV + OPV + OPV). These have been shown
      to provide both individual and collective defence against type 3 poliovirus and
      to reduce the risk for development of the vaccine-associated poliomyelitis.

PMID- 12073272
TI  - [Biochemical markers of toxic and mutagenic complications of cytostatic
      pharmacotherapy].
AB  - Data are submitted on individual prophylaxis of damage to the genetical apparatus
      of bodily normal cells in cytostatic therapy of immunodeficiency states by
      observing changes in biochemical indices, such as activity of enzymes, content of
      biologically active substances and hormones.

PMID- 12073273
TI  - [Effect of neck massage therapy on the soft tissues after thyroid surgery].
AB  - Our objectives in this study were to establish validated methods of massotherapy
      of the neck, to determine its action on the neck structures, and to conduct a
      comparative evaluation of results of the control and study groups after
      performing massotherapy. It has been found out that in 80 (85%) patients the skin
      comes to be tinged with healthy pink, the cutaneous-and-muscle tone getting
      improved, which event makes the skin smooth and elastic following the above
      massage. Over the first ten days of the massoprocedures 44 (48%) subjects
      demonstrated resolution of the edema and swelling, with the thickened skin fold
      as a roller dissappearing by the end of the second month. Dispelling of
      hypothyrosis phenomena made for reduction of dosages of hormonal preparations. We
      consider it mandatory that massotherapy of the neck be instituted in all those
      patients who had undergone operation on the neck and thyroid.

PMID- 12073274
TI  - [Vertebral joint meniscoids in the norm and in functional blocking of the
      vertebral segment].
AB  - Meniscoids have been studied of the intervertebral joints in normal subjects and
      in blocking of the vertebral locomotory segment. Development of changes in
      meniscoids in functional blocking of the vertebral segment is shown as is in
      different degrees of incomplete dislocation in the intervertebral joint. In an
      unremoved blocking of the vertebral segment the soft tissues of the joint
      gradually undergo accelerated dystrophy (the joint capsule, meniscoid, articular
      cartilage). In the early periods of blocking meniscoid becomes hyperplastic
      (edema), it comes to be wedged in the cavity of the joint rendering it immobile.
      The findings secured are helpful when it comes to choosing between different
      policies of managing vertebrogenic disorders and to administering prophylaxis
      thereof.

PMID- 12073275
TI  - [Effect of propranolol on the cardiac rhythm variability and the cardiac cycle
      phase structure in healthy volunteers].
AB  - In an acute pharmacological test in 13 healthy volunteers (24 +/- 4) years old
      effects were studied of propranolol, 40 mg/50 kg body mass, on the sympathovagal
      regulation and phase patterns of the cardiac cycle. The study was made with the
      aid of the computer electrocardiograph "Cardiolab 2000" at the height of the
      propranolol effect by standard methods. The state of the sympathovagal regulation
      was assessed by the heart's rhythm variability technique with respect to the
      spectrum lowfrequency and highfrequency ranges powers. There have been measured
      duration of the P-wave, PQ-interval, QRS-complex, QT-interval to analyze phase
      patterns of the cardiac cycle. One-dose intake of propranolol has been shown to
      optimize the sympathovagal balance by boosting the influence of that portion of
      the autonomic nervous system, whose baseline activity has been shown to be
      slight. Optimization of the sympathovagal balance was accompanied by general
      enhancement of the level of neurohumoral regulation. Effect of propranolol on the
      phase patterns of the cardiac cycle was invariant from the baseline state and
      from subsequent changes in the sympathovagal balance.

PMID- 12073276
TI  - Diabetes mellitus and antipsychotic agents.

PMID- 12073277
TI  - Psychiatric patients' perceptions of constant care.
AB  - 1. Patients need and want structure during CC. 2. Respect for patients
      experiencing CC is demonstrated when caregivers involve patients in all levels of
      decision making. 3. Patients identified the behaviors of caring, health teaching,
      and role modeling as helpful to their recovery. 4. Patients have two primary
      resentments--a lack of privacy and continuity of care.

PMID- 12073278
TI  - Assessment of impulsivity among psychiatric inpatients.
AB  - Routine assessment of impulsivity and accompanying coping skills is essential for
      planning care and appropriate management of patients identified as impulsive.
      Impulsivity can be defined in many ways, and many perspectives exist. Impulsivity
      is associated with several adult psychiatric disorders. In an inpatient
      psychiatric setting, nurses are more likely than members of other disciplines to
      encounter impulsive behavior due to the amount of time spent in direct patient
      care. As the primary caregivers in hospitals, nurses are responsible for the
      management of impulsive individuals. It is critical for treatment plans to
      incorporate interventions specifically targeting impulsivity.

PMID- 12073279
TI  - Working with children with obsessive compulsive disorder.
AB  - 1. Children with OCD are a special challenge for nursing staff. 2. Children with
      OCD often are unable to comply with preexisting behavior management programs at
      child psychiatric units. 3. Each child who enters an inpatient unit must be
      viewed as an individual, separate from his or her diagnosis, and what works for
      one patient with a particular diagnosis may not work for another patient with the
      same diagnosis. 4. A special plan devised with input from the entire nursing team
      is the best way to ensure that continuity of care is carried out among all staff
      on the unit.

PMID- 12073280
TI  - Social function of persons with schizophrenia.
AB  - 1. The social function needs of persons with schizophrenia are similar to those
      of all individuals and include typical social roles, integration and contacts,
      and intimacy and sexual function. 2. Social function is essential to QOL, and
      aspects of social function are determinants of mental health and mental health
      outcomes. 3. Although intimacy and sexual function is found to be an important
      aspect of social function and QOL, health care workers neglect to discuss these
      issues with patients with schizophrenia. 4. Education, support, counseling,
      adequate transportation, safe environments, and treatment plans that include
      appropriate activities are important treatment interventions.

PMID- 12073281
TI  - [Mutations and polymorphisms in CFTR genes in infertile men with oligospermia or
      azoospermia].
AB  - INTRODUCTION: Impaired infertility of the male partner is causative or
      contributOry to in up to one half of all couples unable to conceive
      spontaneously. A considerable number of genes are now known that have an
      essential function in human reproduction and which, when deleted or mutated, can
      cause pathologic changes in the male reproductive system. Congenital bilateral
      absence of the vas deferens (CBAVD) is an important cause of obstructive
      azoospermia in otherwise healthy men. It is also present in 95% of men with an
      autosomal recessive systematic disease--cystic fibrosis. However, clinically
      affected CF patients present a spectrum of genital phenotypes ranging from normal
      fertility to severely impaired spermatogenesis and CBAVD. Cystic fibrosis and
      most cases of CBAVD are caused by mutations in CFTR (cystic fibrosis
      transmembrane conductance regulator) gene. The aim of this study was to test the
      possible involvement of the CFTR gene in the aetiology of male infertility other
      than CBAVD. METHODS: Twenty one infertile men with oligo or azoospermia were
      analysed for the presence of mutations and polymorphisms in the CFTR gene.
      Patients were divided in two groups according to the spermatogram: 1) patients
      with obstructive azoospermia (V < 2 mL, pH < 7.2, low level of a-glucosidase and
      fructose and absence of spermatozoa; 2) patients with impaired spermatogenesis or
      sperm maturation. We performed direct detection for the following mutations:
      delta F508 and delta 1507 (heteroduplex analysis), 621 + 1 G-->T, and N1303K (PSM
      -PCRmediated site-specific mutagenesis), A455E, 1717-1 G-->A, S549N, R560T,
      W1282X, R334W, R347P, R117H, 3849 + 10 kb C-->T and Tn, F508C, 1507V, 1506V
      polymorphisms (reverse dot blot method). G542X, R553X and GSS1D mutations were
      tested by SSCP (Single Strand Conformation Polymorphism). We also performed
      indirect detection of mutations and polymorphisms in 3, 5, 6a, 8, 9, 11, 12, 14a,
      14b, 15, 17b, 18, 20, 21 and 23 exons by DGGE (Denaturant Gradient Gel
      Electrophoresis). Differences between frequencies were tested by chi-square
      statistic, p values of less than 0.05 were considered statistically significant.
      RESULTS: Among 42 chromosomes from infertile men with oligo or azoospermia we
      detected 7 mutations in CFTR gene (16.7%), which was significantly (p = 0.0319)
      more frequent than in general population (2%). Frequency of 5T allele in analysed
      group was high (11.9%) compared to general population (5%), but not statistically
      significant (0.0938). The most common mutation in the group of 10 men with
      obstructive azoospermia was delta F508. It was detected on one chromosome in five
      patients. In three of these patients with 4F508 mutation on the other chromosome
      we found 5T allele on polymorphic Tn locus. In one patient, heterozygous for
      delta F508 mutation, 711 + 3 A-->G mutation on the other chromosome was detected.
      In the group of 11 infertile men with impaired spermatogenesis or sperm
      maturation we detected one mutation--delta F508. Two patients from this group had
      5T variant on one chromosome. DISCUSSION: We analysed 21 infertile men with oligo
      or azoospermia not caused by endocrine or inflammatory character, or chromosome
      mutations. Within this group frequency of CFTR mutations was increased compared
      to general population (p = 0.0319), suggesting that CFTR gene may be involved in
      the aetiology of infertility in men with oligo or azOospermia. In the group of
      patients with obstructive azoospermia 50% had at least one mutation, but only 10%
      had mutations in both chromosomes. One of the possible explanations would be that
      mutations are in the promoter region, introns or exons that were not included in
      analyses. The second explanation could be that some cases of obstructive
      azoospermia are only partially (or not) related to CFTR gene. In the group of
      patients with impaired spermatogenesis or sperm maturation, the frequencies of
      CFTR mutations and 5T allele were also increased compared to general population,
      but lower than in the group with obstructive azoospermia. This fact could mean
      that the influence of some other genes is higher in this condition than in the
      case of obstructive azoospermia. CONCLUSION: We concluded that CFTR gene plays a
      role in the aetiology of obstructive azoospermia and that is also could be
      involved in some cases of impaired spermatogenesis and sperm maturation. Due to
      the high incidence of CFTR mutations in patients with obstructive azoospermia we
      suggest screening of CFTR mutations before assisted reproduction.

PMID- 12073282
TI  - [Topography and asymmetry of the visual response in electroencephalographic power
      spectra in healthy children].
AB  - In order to quantify the visual reactivity of EEG to opening the eyes, the
      topography of EEG power spectra in a sample of 72 healthy subjects aged from 7-15
      years, was studied. The EEGs were recorder at 14 scalp sites under eyes closed
      (ECL) and eyes open (EOP). It has been established that the absolute powers in
      total and in alpha band were significantly higher in all derivations under ECL as
      compared with EOP condition. Except for the frontal derivations, absolute power
      in theta band under ECL condition was significantly higher than that under EOP
      condition. Changes in delta and beta powers were seldom significant. In beta 2
      band no EEG blocking was noticed in anterior area. Opening the eyes significantly
      influenced the values of asymmetry index in alpha band and total power. In all
      frequency bands and under both conditions, the differences of powers between the
      hemispheres were found mainly in the prefrontal and laterofrontal areas. The
      results showed that the visual blocking of EEG was mostly due to a higher degree
      of EEG desynchronization after opening the eyes.

PMID- 12073283
TI  - [A practical study of the efficacy of a delayed-action preparation of
      carbamazepine (Tegretol CR 400) in the treatment of patients with partial
      epilepsy ].
AB  - INTRODUCTION: Carbamazepine (CBZ) is the first choice antiepileptic drug in the
      treatment of partial seizures. Many clinical studies show high efficacy and good
      tolerance of CBZ in the majority of patients. However, poor water solubility and
      erratic absorption as well as autoinduction of its metabolism, cause wide and
      unpredictable fluctuations in CBZ serum concentration. In order to avoid these
      problems controlled-release formulations of CBZ (Tegretol CR 400) were developed.
      PURPOSE: The aim of this study was to evaluate the efficacy, tolerance and
      practicality of the therapy of partial seizures in adults with controlled-release
      CBZ (Tegretol CR 400). PATIENTS AND METHODS: Over a three-year period we
      conducted an open pragmatic study of controlled-release CBZ in the therapy of 141
      adult patients with established diagnosis of localized related epilepsy. Patients
      with progressive brain or systemic disease were excluded. All patients had
      unacceptable seizure frequency and were divided into four groups: 1) 34 with
      newly-diagnosed epilepsy; 2) 42 with chronic epilepsy and no previous
      antiepileptic medication; 3) 27 with chronic epilepsy previously treated with
      conventional preparations of carbamazepine (CBZ); and 4) 38 with chronic epilepsy
      previously treated with other antiepileptic medications. Patients were switched
      to controlled-release CBZ and the dosage was slowly adjusted. Baseline evaluation
      included the analysis of efficacy, tolerance and practicality of the controlled
      release CBZ therapy. Three categories of efficiency were defined: 1) successful
      (patients without seizures); 2) partially successful (patients with improvement
      of at least 50% in frequency and severity of seizures); and 3) unsuccessful
      therapy (same or worse than before controlled-release CBZ). Tolerance and
      practicity were evaluated through the analysis of side effects and frequency of
      daily doses, respectively. These variables were compared to the corresponding
      ones after a period of at least three months of full dosage controlled-release
      CBZ therapy. RESULTS: In all four groups the therapy was successful in 76%, 52%,
      30% and 29%, partially successful in 18%, 43%, 30% and 32%, and unsuccessful in
      6%, S%, 40% and 39%, respectfully. Side effects occurred less frequently in all 4
      groups during the therapy with controlled-release CBZ. We found reduced frequency
      of drug administration (once or twice daily) in 97.9% of our patients.
      DISCUSSION: Due to its slow and irregular absorption, short half life, wide and
      unpredictable fluctuation in plasma levels CBZ has decreased ability to control
      seizures, with the appearance of the intermittent side-effects such as diplopia,
      ataxia, headache and dizziness. Controlled-release formulation of CBZ sustains
      stable absorption and reduces fluctuations in carbamazepine serum concentration.
      Steady serum levels permit to the majority of patients to tolerate a higher total
      daily dose by reducing peak-dependent side-effects and improve compliance as a
      result of less frequent daily doses (1 or 2). CONCLUSION: In patients with
      partial seizures controlled-release vs. conventional carbamazepine had better
      efficiency, based on an excellent tolerance, favorable daily dosage and superior
      compliance.

PMID- 12073284
TI  - [An obturator or "lateral" bypass in infected vascular prostheses in the groin?].
AB  - The infection of the previously implanted vascular graft at the groin, is
      associated with great mortality and morbidity rate [1]. The authors present a
      retrospective study in which they analyzed management of infected vascular
      prostheses at the groin, using obturator bypass in 26 cases, and "lateral" bypass
      in 15 cases. The indications for obturator bypass reconstructions included: 20
      infections of aorto-femoral grafts, two infected pseudoaneurysms in the groin
      after PTA of the superficial femoral artery, and 4 infections of iliac-femoral
      grafts. The indications for lateral bypass reconstructions were: infections after
      aorto-femoral reconstructions--8 cases; infection after femoro-popliteal
      reconstructions--4 cases; infection after iliac-femoral reconstruction--2
      patients, and one infected pseudoaneurysm in the groin after PTA of the
      superficial femoral artery. In 3 subjects obturator bypass was performed using
      extraperitoneal approach, while in other 23 patients transperitoneal approach was
      done by donor's artery. The obturator bypass was performed using a PTFE graft in
      3 cases, and Dacron graft in 23. The donor's artery used for obturator bypass was
      a noninfected proximal part of aortofemoral graft in 20 cases, and iliac artery
      in 6 patients. The superficial femoral artery was recipient artery for obturator
      bypass in 3 cases, deep femoral artery in one case, and above the knee popliteal
      artery in 22 cases (Figure 1). In two patients transperitoneal approach to donors
      artery for "lateral" bypass has been used, and in 13 cases extraperitoneal. The
      proximal noninfected part of aorto femoral graft was used as a donor's artery for
      lateral bypass in 8 patients, while common iliac artery in 7 subjects. In 5 cases
      reconstructions were performed using PTFE grafts, in 3 using autologous saphenous
      vein grafts, and in 7 using Dacron grafts. The recipient artery for "lateral"
      bypass was deep femoral in 8 cases, superficial femoral in three patients and
      above the knee popliteal artery in 4 subjects. After both types of
      reconstruction, extirpation of infected grafts from the groin was performed
      (Figure 2). The control examination was performed using physical and Doppler
      ultrasonographic examinations, one, 3, 6, 12 months, and then every year after
      the operation. In cases with suspected graft infection or thrombosis, control
      angiography was also performed. One intraoperative perforation of the urinary
      bladder has been done accidentally during obturator bypass reconstruction. The
      mean follow-up period for patients with obturator bypasses was 2.3 years, while
      2.1 years for patients with "lateral" bypasses. Comparing with "lateral" bypass,
      obturator bypass showed statistically significant lower (p < 0.05) 30-day
      mortality and early graft infection rate, as well as statistically significant
      better early and total limb salvage rate. There were no statistically significant
      differences (p > 0.05) between obturator and "lateral" bypass procedures, having
      in mind, late graft infection rate, as well as early and late graft patency
      (Figures 3 and 4). In cases with infected vascular prostheses in the groin, the
      authors recommend obturator bypass comparing with "lateral" bypass.

PMID- 12073285
TI  - [Fibroma of the root of small intestine mesentery].
AB  - Fibromas are rarely localized in the abdomen, but almost always in the mesentery
      or omentum. We present a 63-year old woman in whom the examination of the upper
      abdominal pain showed a well distinct abdominal mass at the level of the lower
      edge of the pancreas. During the operation a tumour, 100 x 87 x 70 mm in size,
      from the radix of small bowel mesentery, was excised. Seven months later the
      patient is symptom-free with normal ultrasonographic and CT findings.

PMID- 12073287
TI  - [Theoretic approach to motivation in teamwork].

PMID- 12073286
TI  - [Protein S and pregnancy].
AB  - Protein S is a cofactor of protein C which lowers the activated factors VIII and
      V. Pregnancy reduces the level of protein S to 40-50% of normal levels but it is
      not clear whether the lowered protein S levels increase the risk of developing
      thrombo-embolism during pregnancy. This is a report of a 39-year old woman,
      multipara whose pregnancy terminated as IUGR and who had previously two
      stillbirths. After the third pregnancy loss of functional protein S level was
      20%. Two months after delivery protein S activity was 60%. As it was suspected
      that low protein S level was a risk factor of complications in pregnancy
      anticoagulant therapy was used. Thereafter, pregnancy and delivery at 38.5 weeks
      of gestation were successful and the baby weighted 3400 gr at birth. The aim of
      this report is to emphasize the important role of follow-up of the level of
      protein S in pregnancy in order to avoid the risk of thrombo-embolism in
      pregnancy. Anticoagulant therapy is very successful in such a pregnancy and may
      ensure safe birth.

PMID- 12073289
TI  - [Development of female and male identity: sex differentiation].

PMID- 12073288
TI  - [The Brugada syndrome].

PMID- 12073290
TI  - [Ethical and legal dilemmas in the treatment of infertility at the beginning of
      the new millennium].

PMID- 12073291
TI  - [A forensic medical examination of an exhumation in the first half of the 19th
      century in Montenegro].
AB  - Seven years after the homicide, the court ordered exhumation and expertise of the
      cranium. The well-known physician and surgeon Yovo Ilichkovitsh, who took part in
      many campaigns during the 19th Century and treated successfully complicated
      wounds and fractures, was appointed to examine the skull. He concluded that the
      bullet had entered the cranium from the back. The finding was based on the fact
      that bullet-hole was smaller than that at the exit. The event took place in
      Montenegro before 1850, being the first reported forensic expertise in this
      region.

PMID- 12073292
TI  - [Changes in calcium levels in blood and urine during various regimens of table
      salt intake in patients with essential arterial hypertension].
AB  - INTRODUCTION: It has been reported that changes in salt loading influence
      parameters of calcium metabolism in hypertensive subjects. It was also reported
      that response of blood pressure to salt intake is related to salt-induced
      increase in intracellular calcium and decrease in intracellular magnesium
      concentrations [1]. Several authors showed that salt-sensitive hypertensive
      subjects significantly decreased blood pressure after calcium intake which was
      emphasized by high salt intake. Resnick et al. showed that during high salt
      intake regimen increase in blood pressure was followed with decrease in serum
      calcium level, this was explained by the fact that high salt intake stimulates
      the calcium uptake by cells [2]. They also reported the following characteristics
      of hypertensive patients with additionally lower blood pressure as a response to
      calcium intake: salt-sensitive, low serum ionized calcium and plasma renin
      activity (PRA) values and high parathyroid hormonE (PTH) values and 1.25-(OH)2-D
      values. The aim of the study was to evaluate values of corrected and ionized
      serum and urine calcium in a group of salt-sensitive patients, salt-resistant
      patients and a whole group during normal salt-intake regimen, and a group without
      salt and during sodium load (10 g salt extra). MATERIAL AND METHODS: In our
      study, 50 untreated patients (27 women and 23 men; average age 42 +/- 9.2 yrs;
      average BMI 27.91 +/- 4.6 kg/m2) with essential hypertension were put on a high
      salt regimen (200 mmol NaCl per day) for one week after a week on a low salt diet
      (20 mmol NaCl per day). On the last day of the normal regimen and during the 1st,
      3rd and 5th day of low salt and high salt regimens, the following follow-up was
      carried out: total (corrected) serum calcium level and total urine calcium level,
      ionized serum calcium urine creatininE level; serum albumin and daily diuresis
      and blood pressure. All patients had normal sodium and potassium serum
      concentrations. Salt intake was checked by taking a specimen of 24-hour urine
      considered as satisfactory if sodium excretion of 100 to 150 mmol/d (mmol per
      day) was noted. During the whole hospital examination, calcium intake through
      hospital meals was standardized to about 817 mg of calcium daily. Salt
      sensitivity was defined as 10 mmHg increase in mean blood pressure at the end of
      high vs. low salt diet. Salt sensitive group consisted of 26 patients and salt
      insensitive of 24 patients. RESULTS: According to sex, there was no statistically
      significant difference: 27 females (54%) and 24 males (46%). Average age of
      patients was 49 +/- 9.2 yrs, ranging from 21 to 64 with normal frequency
      distribution. Average body weight was 80.49 kg +/- 12.45 kg. Body height was from
      150 to 192 cm with average of 170.12 +/- 10.53 cm. Average value of Body Mass
      Index (BMI in kg per square meter) was 27.91 +/- 4.6. In the studied patients
      average duration of hypertension was 6.98 +/- 6.4 yrs with non-homogeneous
      distribution. In 32 patients (64%) the medical history confirmed that one or more
      family members had hypertension. It was found that salt loading significantly
      decreased ionized calcium (F = 2.49; p < 0.05) and significantly increased
      urinary excretion of calcium (F = 5.22; p < 0.001) in salt sensitive patients in
      comparison with salt insensitive subjects. Serum calcium did not differ
      significantly during different salt intake regimens between two groups. Our study
      revealed no positive correlation between gender, age, BMI and family history and
      calcium metabolism. CONCLUSION: The findings of this study support the opinion of
      altered calcium metabolism in hypertensive subjects sensitive to salt intake. By
      demonstrated results we tried to define clinically different pathophysiologic and
      potentially different therapeutic subgroups in hypertensive population and to
      point to clinical and biochemical heterogeneity of primary hypertension.

PMID- 12073293
TI  - Knowledge about pulse oximetry among medical and nursing staff.
AB  - The use of the pulse oximeter is becoming popular in developing countries. The
      introduction of the requirement into hospitals is not usually accompanied by
      appropriate staff training. Therefore 25 health care professionals at the Obafemi
      Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria, were
      studied to assess their knowledge about the pulse oximeter. A questionnaire was
      designed to assess this. A 100% response rate was achieved from staff
      participating in the study. Most (92%) of the participants (medical (M) 44%,
      nursing (N) 52% and medical student (MS) 4% had seen the equipment before, being
      used in the hospital. Only 28% claimed to have been trained in its use though.
      The answers to the clinical questions generally reflected a poor understanding of
      the principles of pulse oximetry. The aim of improving patient's care by
      introducing such equipment can only be achieved by accompanying its introduction
      with staff training on the use of this equipment.

PMID- 12073294
TI  - Uterine fibroids: a ten-year clinical review in Ilorin, Nigeria.
AB  - A retrospective study to determine the incidence, clinical presentation and
      management of uterine fibromyoma at the University of Ilorin Teaching Hospital,
      Ilorin, Nigeria. Five hundred and sixty-nine consecutive cases of histologically
      confirmed uterine fibroid over a ten-year period were reviewed. Uterine
      fibromyoma constituted 13.4% of gynaecological admission and was responsible for
      26.2% of major gynaecological surgery. Majority of the patients (78.4%) were aged
      between 30 and 44 years and 60.8% were of low parity (0-2). The common
      presentations were menstrual disorders (64.3%), infertility (56.2%) and lower
      abdominal swelling (35.5%). Hypertension was present in 26.5% and 42% were obese.
      Pelvic adhesion was noted in 58.9% of patients. Total abdominal hysterectomy was
      the surgical procedure in 52% of cases. Pyrexia (32.5%), Anaemia (29.3%),
      Prolonged hospital stay (24.1%) and Wound infection (20.2%) were the common
      postoperative morbidities. Fibromyoma at the University of Ilorin Teaching
      Hospital follows a pattern similar to other parts of the world. It is responsible
      for a number of gynaecological complaints. Surgery still remains the main mode of
      treatment.

PMID- 12073296
TI  - Glomerular filtration rate in Nigerian children with homozygous sickle cell
      disease.
AB  - The study proposed to assess glomerular filtration rate as determined by
      endogenous creatinine clearance in steady state Nigeria children with homozygous
      sickle cell disease and normal controls. Twenty-four hours urinary creatinine
      clearance was estimated over a 6-month period in 54 steady-state homozygous
      sickle cell disease and 57 normal control children aged 5 to 13 years. Each child
      was admitted and a 24-hour urine sample (8.00 am to 8.00 am) was collected both
      for volume measurement and creatinine concentration determination. Blood was also
      collected from each child 30 minutes to end of urine collection for plasma
      creatinine concentration determination, haematocrit and reticulocyte counts. The
      results were compared between the two groups of children using student's t-test
      and the chi (X2) square test where necessary. The mean glomerular filtration
      rates +/- SD (ml/min/1.73 M2) for homozygous sickle cell disease children and
      normal controls were not significantly different (p > 0.05). Glomerular
      filtration rate did not differ significantly between the age groups in both
      patients and normal controls; haematocrits correlated weakly with glomerular
      filtration rates in the patients (r = +0.213; p < 0.001). Nigerian children with
      homozygous sickle cell disease who are in steady states have normal glomerular
      filtration rate that is hardly influenced by increasing age and low haematocrit
      level.

PMID- 12073295
TI  - Seminal fluid indices of men attending infertility clinic at St. Charles Borromeo
      Hospital, Onitsha, Nigeria (1994-1998).
AB  - The result of seminal fluid analysis of 628 men attending an infertility clinic
      in Onitsha, between 1994-1998; were collated and analysed. The result showed that
      62.7% (n = 3394) had normal sperm density, while 37% (n = 234) of the men, had
      sperm density less than 20 million per ml ejaculate. 6.2% (n = 39) of these
      patients were azoospermic. 44% (n = 270) of these patients had sperm motility
      that was less than 50% while 20.5% (n = 129) of the samples contained pathogens,
      with commonest pathogen being staphylococus aureus in 46% (n = 60) of the sampled
      patients with pathogens. This high rate of oligospermia and azoospermia calls for
      proper education of the populace as regards, prevention and treatment of sexually
      transmitted diseases and urinary tract infections. Also, there is the urgent need
      to establish centres for assisted reproduction, which will help in solving the
      already overwhelming problem of infertility in our community.

PMID- 12073297
TI  - Eye injuries in the young in Ile-Ife, Nigeria.
AB  - One hundred and seventeen children aged 0-17 years treated for eye injuries at
      the Obafemi Awolowo University Teaching Hospital Ile-Ife, Nigeria were studied.
      Seventy-five were males and 42 were females with a mean age of 10 years 4 months.
      Injuries occurred with increasing frequency after the age of 4 years and were
      commonly sustained by children at play (50.4%); during corporal punishment
      (10.3%); assault (9.4%) and street hawking (9.4%). Causative agents were mostly
      sticks and twigs, followed by missiles and fall. Visual prognosis was best in
      patients with contusion injuries (48.3%) and worst in those with perforating eye
      injuries (30.5%). Blindness of the injured eye occurred in one-third of the
      patients and another 17.5% had significant visual impairment. This study shows a
      variation in the aetiology and visual outcome of eye injuries in the young.
      Strategies for the prevention of eye injuries are mainly health education,
      improved supervision of children at play, change in the method of corporal
      punishment and provision of protective devices for adolescents at work. Early
      diagnosis and prompt management will improve visual prognosis.

PMID- 12073298
TI  - Childhood burn injuries in north western Nigeria.
AB  - This 2-Year (1999-2000) prospective study was undertaken to determine the pattern
      and outcome of childhood burns at the Usmanu Danfodio University Teaching
      Hospital Sokoto, North Western Nigeria. A total of 108 children, 15 years and
      below, were seen. There were 67 males and 41 females giving a male to female
      ratio of 1.6:1. Domestic accidents were responsible for 100 (92.6%) cases. Hot
      liquids as the agents of injuries were recorded in 72 (66.7%) children. The
      mortality rate was 6.5% (7 cases), all males. Petrol explosion was responsible
      for 4 deaths. Another case is made for the reduction in the incidence, morbidity
      and mortality of burns by elevating the socio economic status of the community.

PMID- 12073299
TI  - Fregoli syndrome: a rare persecutory delusion in a 17 year old sufferer of
      psychosis associated with typhoid fever at Jos University Teaching Hospital, Jos,
      Nigeria.
AB  - This paper describes a rare delusional disorder, the Fregoli syndrome, in a 17
      year old girl who suffered from typhoid psychosis as seen at the Psychiatric Unit
      of the Jos University Teaching Hospital, Jos.

PMID- 12073300
TI  - The challenges of postgraduate medical training in Nigeria: the past, present and
      future.

PMID- 12073301
TI  - Vitamin A deficiency in Nigeria.
AB  - Childhood blindness is second only to cataract in magnitude of world blindness
      when the "blind years" is considered. The "blind years" is the number of years a
      person lives with blindness. Studies have shown that over 34%-69% of childhood
      blindness in Nigeria is caused by corneal opacity, which results mainly from an
      interplay of vitamin A deficiency, measles and harmful traditional eye practices.
      However, vitamin A deficiency which manifests in the eye as xerophthalmia is the
      dominant problem in these children. The purpose of this review is to stress the
      importance of xerophthalmia, which is of public health significance, as an
      important cause of childhood blindness in Nigeria. Studies involving surveys of
      xerophthalmia, childhood and nutritional blindness are reviewed with data
      extracted from a nationwide survey on prevalence of xerophthalmia. The likely
      explanation for vitamin A deficiency in Nigerian children is discussed with
      possible solutions and recommendations made to control this avoidable and
      devastating cause of blindness.

PMID- 12073302
TI  - Routine medical examination of food vendors in secondary schools in Ilorin.
AB  - Street vended food is expanding in developing countries, but the safety of the
      food provided is doubtful. Hence there is need for this trade to be regulated.
      One of the common ways of regulating them in the developing countries is through
      medical examination of food vendors, which some international agencies have
      condemned because of its inefficiency in controlling food contamination and food
      borne diseases. This study was done to determine medical examination practices
      among the food vendors and to see whether the practice ensures food safety. A
      cross-sectional study of 185 food vendors in 58 secondary schools within the
      study area was conducted using a structured questionnaire and a checklist. 141
      (76.2%) respondents had medical test done prior to [not readable: see text]
      employment. The medical examination was requested for usually by the principals
      (51.9%), schoolteachers (37.8%) and the school clinic staffs [not readable: see
      text]). The test carried out on these vendors are physical examination, stool and
      urine examinations for parasites. Periodic medical examination among the vendors
      are low with only 30 (21.3%) of the 141 vendors having undergone periodic
      examinations. Majority of the respondents (77.5%) did not report to the school
      authorities or present at the school clinics when ill. Lack of fund and non
      compulsion of medical examination by the school authorities were some of the
      reasons given by the respondents for not undergoing medical test. Present
      practice of medical examination among the food vendors is not enough to ensure
      food safety. There is need to improve on this practice, if the policy of routine
      medical examination for food vendors is to be useful in controlling food borne
      diseases.

PMID- 12073303
TI  - Parish nurse practice with client aggregates.
AB  - The purpose of this study was to describe 1 aspect of parish nurses' practice:
      working with client aggregates. Nineteen parish nurses practicing in 22 faith
      communities collected data using 2 standardized nursing classification systems-
      North American Nurses Diagnosis Association Taxonomy and Nursing Intervention
      Classification. Nurses recorded 77 group encounters for services provided over a
      5-month period. The most frequent nursing diagnoses and nursing interventions are
      reported and emphasize health promotion and illness prevention. The parish nurse
      roles of educator, counselor, referral agent, and advocate-facilitator described
      in the literature were consistent with the findings of this study. In addition,
      the parish nurse as a member of the ministerial team is discussed. A focus group
      of the parish nurses provided validation of the results of aggregate practice.

PMID- 12073304
TI  - Knowledge, attitudes, and behavior related to pregnancy in a rural teenage
      population.
AB  - Despite recent declining national trends, teenage pregnancy continues to be a
      community health problem warranting attention, especially in rural areas of the
      southern United States. Communities are unique and require assessment of risk
      populations to develop appropriate initiatives. This pilot study examined consent
      strategies and survey procedures and tools. Additionally, descriptive statistics
      related to pregnancy and pregnancy prevention knowledge, attitudes, and behaviors
      were examined. The study sample consisted of 52 boys and girls who perceived
      themselves to be in the middle or upper levels of their 9th-grade class and who
      were predominantly college bound and fairly active in extracurricular activities.
      Often groups with similar demographics are not perceived as at risk for pregnancy
      and early sexual intercourse, but the findings suggest otherwise. Many girls were
      sexually active, several had already experienced pregnancy, and some were at risk
      for intentional pregnancy. Knowledge regarding pregnancy prevention was modest.
      School-based and peer-focused programs are promising intervention strategies in
      response to identified attitudes and reported information sources related to
      pregnancy and pregnancy prevention.

PMID- 12073305
TI  - Characteristics of smoking in low-income pregnant Latina and white women.
AB  - Smoking during pregnancy is hazardous as it poses numerous risks to both the
      mother and the unborn child. Formerly, interventions that were successful for
      White smokers were thought to be equally appropriate for all smokers. It is now
      acknowledged that there is a need to tailor interventions for distinct ethnic and
      cultural groups. This study was designed to identify variables that are
      associated with smoking status in a low-income sample of pregnant Latina and
      White women. Results indicate that Latinas had lower levels of addiction to
      cigarettes and were less likely to have partners who smoked than White women.
      Identifying differences in the characteristics of ethnically diverse pregnant
      smokers will assist in the development of interventions that are tailored for
      women who attend prenatal clinics.

PMID- 12073306
TI  - Compliance of licensed child care centers with the American Academy of
      Pediatrics' recommendations for infant sleep positions.
AB  - Sudden Infant Death Syndrome is an elusive and tragic cause of infant mortality.
      In 1992, the American Academy of Pediatrics (AAP) recommended that healthy term
      infants be placed in the supine or lateral positions for sleep, based on research
      conducted in Europe, Australia, and New Zealand. The AAP modified its
      recommendation in 1994, indicating a preference for the supine position. Since
      the initial AAP proposal, national educational programs have worked to encourage
      parents and health care providers to utilize AAP guidelines. Studies have been
      done on parental use of the supine position. However, very little information
      exists about the procedures utilized in licensed child care facilities. A survey
      of child care providers was conducted to determine the risk for Sudden Infant
      Death Syndrome, as indicated by rates of compliance with AAP guidelines. Results
      show that although the majority of the child care providers knew the AAP
      recommendations, only 14.3% were in complete compliance. We make recommendations
      for the role of the public health nurse in facilitating compliance in child care
      centers along with suggestions for future research.

PMID- 12073307
TI  - Integrating health promotion into nursing curricula in Hong Kong.
AB  - The health care system in Hong Kong has historically been steeped in the
      biomedical paradigm. Health care reform, however, is finally putting health
      promotion on the agenda of governments and health care providers. As the largest
      group of providers in Hong Kong, nurses must assume a leadership role in the
      transition of the current illness-focused system to one that emphasizes health
      and promotes wellness. For nurses to take up the challenge of health promotion,
      they need to acquire the requisite knowledge and skills. Nursing curricula must
      emphasize this new paradigm and provide opportunities for students to develop
      expertise in health promotion and disease prevention. This article describes a
      health-promotion initiative carried out by 1st-year students in an undergraduate
      nursing program in Hong Kong. The health-promotion project aims to prepare
      graduates who will be able to meet health care needs and function effectively in
      the future health care system. Not only will these nurses be capable of becoming
      future leaders of the health-promotion movement in Hong Kong, they are also
      contributing to the health and wellness of Hong Kong citizens.

PMID- 12073308
TI  - LacZ assays in yeast.

PMID- 12073309
TI  - Analysis of budding patterns.

PMID- 12073310
TI  - Uses and abuses of HO endonuclease.

PMID- 12073311
TI  - Assays for gene silencing in yeast.

PMID- 12073312
TI  - Classical mutagenesis techniques.

PMID- 12073313
TI  - Introduction of point mutations into cloned genes.

PMID- 12073314
TI  - Insertional mutagenesis: transposon-insertion libraries as mutagens in yeast.

PMID- 12073315
TI  - Tn7-mediated mutagenesis of Saccharomyces cerevisiae genomic DNA in vitro.

PMID- 12073316
TI  - Vector systems for heterologous expression of proteins in Saccharomyces
      cerevisiae.

PMID- 12073317
TI  - Cloning-free genome alterations in Saccharomyces cerevisiae using adaptamer
      mediated PCR.
AB  - Each of the adaptamer-directed genome manipulation methods is predicated on the
      fact that recombination between two DNAs is enhanced by increasing the length of
      homology. Many of the current PCR-based genome manipulation techniques rely on
      very short homologies to promote recombination. In these cases homology length is
      dictated by the technical limits of oligonucleotide synthesis. Adaptamers
      circumvent this problem since long homology regions are produced in a first round
      of PCR, and then fused to the selectable marker in a second round of PCR via
      complementary sequence tags on the adaptamers. Furthermore, many of the
      techniques described here rely on preexisting and commercially available
      adaptamer sets that can be obtained inexpensively rather than designing new
      primers for every experiment. Although a cost is incurred when performing
      multiple PCR amplifications, the increase in recombination efficiency is
      dramatic. Finally, the adaptamer-mediated PCR fusion methodology is versatile and
      can be applied to varied genome manipulations.

PMID- 12073318
TI  - Kar-mediated plasmid transfer between yeast strains: alternative to traditional
      transformation methods.

PMID- 12073319
TI  - Gene disruption.

PMID- 12073320
TI  - Getting started with yeast.

PMID- 12073321
TI  - Synthetic dosage lethality.

PMID- 12073322
TI  - Saccharomyces Genome Database.

PMID- 12073323
TI  - Three yeast proteome databases: YPD, PombePD, and CalPD (MycoPathPD).

PMID- 12073324
TI  - Database resources relevant to yeast biology.

PMID- 12073325
TI  - Searching yeast intron data at Ares lab Web site.

PMID- 12073327
TI  - Transcriptome analysis of Saccharomyces cerevisiae using serial analysis of gene
      expression.

PMID- 12073326
TI  - Yeast genomic expression studies using DNA microarrays.
AB  - The exploration and characterization of yeast genomic expression programs is
      providing a wealth of information about yeast biology, as well as other
      organisms. The intriguing biology of yeast species invites characterization of
      genomic expression patterns to illuminate the details of cellular physiology. In
      addition to its value as an interesting organism, yeast maintains its role as an
      excellent model in which to characterize genomic expression programs. Microarray
      studies are quickly spreading to plant, animal, and microbial organisms that
      remain in the early stages of characterization. The extensive knowledge of yeast
      biology, as well as the relative ease with which yeast studies can be performed
      and controlled, facilitates interpretation of the genomic expression data.
      Importantly, existing information about yeast biology, including functional
      annotations for each gene, is captured and efficiently presented in databases
      such as the Saccharomyces Genome Database (SGD), the Munich Information Center
      Yeast Genome Database (MIPS), the Yeast and Pombe Protein Databases (YPD and PPD,
      respectively), and others. A number of databases also allow the exploration of
      published genomic expression studies, including the "Expression Connection" at
      SGD and the Microarray Global Viewer (yMGV) organized by Marc et al. Consulting
      these databases to retrieve known details about gene function and regulation
      vastly facilitates interpretation of the genomic expression data, allowing
      biological hypotheses to be formulated and tested. These hypotheses can be
      applied to other organisms that may execute genomic expression programs similar
      to those seen in yeast. Furthermore, as more genomic expression studies in
      multiple organisms emerge, large-scale data comparisons can be conducted, within
      and across organisms. Incorporating the results of yeast studies into such
      comparisons is certain to increase our understanding about the function,
      regulation, and evolution of genomic expression programs.

PMID- 12073328
TI  - How to set up a yeast laboratory.

PMID- 12073329
TI  - PCR-based engineering of yeast genome.

PMID- 12073330
TI  - ChIP-chip: a genomic approach for identifying transcription factor binding sites.

PMID- 12073331
TI  - Computational approaches to identifying transcription factor binding sites in
      yeast genome.

PMID- 12073332
TI  - Array-based methods for identifying protein-protein and protein-nucleic acid
      interactions.

PMID- 12073333
TI  - Building protein-protein networks by two-hybrid mating strategy.

PMID- 12073334
TI  - Integrated version of reverse two-hybrid system for the postproteomic era.

PMID- 12073335
TI  - Biochemical genomics approach to map activities to genes.

PMID- 12073336
TI  - Use of two-dimensional gels in yeast proteomics.

PMID- 12073337
TI  - Constructing yeast libraries.

PMID- 12073338
TI  - Transformation of yeast by lithium acetate/single-stranded carrier
      DNA/polyethylene glycol method.
AB  - In this chapter we have provided instructions for transforming yeast by a number
      of variations of the LiAc/SS-DNA/PEG method for a number of different
      applications. The rapid transformation protocol is used when small numbers of
      transformants are required. The high efficiency transformation protocol is used
      to generate large numbers of transformants or to deliver DNA constructs or
      oligonucleotides into the yeast cell. The large-scale transformation protocol is
      primarily applicable to the analysis of complex plasmid DNA libraries, such as
      those required for the yeast two-hybrid system. The microtiter plate versions of
      the rapid and high efficiency transformation protocols can be applied to high
      throughput screening technologies.

PMID- 12073340
TI  - Vacuolar proteases and proteolytic artifacts in Saccharomyces cerevisiae.

PMID- 12073339
TI  - Genetic transformation of Saccharomyces cerevisiae mitochondria.

PMID- 12073341
TI  - Analysis of the size and shape of protein complexes from yeast.

PMID- 12073342
TI  - Quantitative microscopy of green fluorescent protein-labeled yeast.

PMID- 12073343
TI  - Purification of glutathione S-transferase fusion proteins from yeast.

PMID- 12073344
TI  - Protein- and immunoaffinity purification of multiprotein complexes.

PMID- 12073345
TI  - In vitro DNA replication assays in yeast extracts.

PMID- 12073346
TI  - Yeast pre-mRNA splicing: methods, mechanisms, and machinery.

PMID- 12073347
TI  - Analysis and reconstitution of translation initiation in vitro.

PMID- 12073348
TI  - Assaying protein ubiquitination in Saccharomyces cerevisiae.

PMID- 12073349
TI  - Vesicle budding from endoplasmic reticulum.

PMID- 12073350
TI  - Mapping phosphorylation sites in proteins by mass spectrometry.

PMID- 12073351
TI  - Identification of yeast proteins by mass spectrometry.

PMID- 12073352
TI  - Digital time-lapse microscopy of yeast cell growth.

PMID- 12073353
TI  - Subcellular fractionation of secretory organelles.

PMID- 12073355
TI  - Fluorescence resonance energy transfer using color variants of green fluorescent
      protein.

PMID- 12073354
TI  - Plasma membrane biogenesis.

PMID- 12073356
TI  - Separation of Golgi and endosomal compartments.

PMID- 12073357
TI  - Visualization and purification of yeast peroxisomes.

PMID- 12073358
TI  - Studying the behavior of mitochondria.

PMID- 12073359
TI  - Isolation of nuclear envelope from Saccharomyces cerevisiae.

PMID- 12073360
TI  - Studying yeast vacuoles.

PMID- 12073361
TI  - Purification of yeast actin and actin-associated proteins.

PMID- 12073363
TI  - Synchronization procedures.

PMID- 12073362
TI  - Identifying functional interactions with molecular chaperones.

PMID- 12073364
TI  - Separation of mother and daughter cells.

PMID- 12073365
TI  - Assays of cell and nuclear fusion.

PMID- 12073366
TI  - Analysis of prion factors in yeast.

PMID- 12073367
TI  - Immunoelectron microscopy of aldehyde-fixed yeast cells.

PMID- 12073368
TI  - Assaying replication fork direction and migration rates.

PMID- 12073369
TI  - Analysis of RNA export.

PMID- 12073370
TI  - Nuclear protein transport.

PMID- 12073371
TI  - How to monitor nuclear shuttling.

PMID- 12073372
TI  - Flow cytometry/cell sorting for isolating membrane trafficking mutants in yeast.

PMID- 12073374
TI  - Monitoring protein degradation.

PMID- 12073373
TI  - Protein synthesis assayed by electroporation of mRNA in Saccharomyces cerevisiae.

PMID- 12073375
TI  - Analyzing mRNA decay in Saccharomyces cerevisiae.

PMID- 12073378
TI  - Cryomethods for thin section electron microscopy.

PMID- 12073377
TI  - Electron tomography of yeast cells.

PMID- 12073376
TI  - Use of green fluorescent protein in living yeast cells.

PMID- 12073379
TI  - Amgen warns of fake Epogen vials in U.S.

PMID- 12073380
TI  - The value of staff surveys in improving communication, retaining staff.

PMID- 12073381
TI  - A patient's view on health. Spring training: a thoughtful approach.
AB  - As I write this, the weather is still cold and dry in the Pacific Northwest. The
      Olympics are history, and a slow transition is being made from indoor winter
      sports to outdoor spring sports. As I rush my son from his basketball game to an
      early season baseball practice, I myself am starting to feel the anticipation of
      another season on the baseball diamond.

PMID- 12073382
TI  - Are catheter design & implantation practices discouraging PD use?

PMID- 12073383
TI  - Advocating for change in nephrology social work practice--Part II: The survey.

PMID- 12073384
TI  - EDTNA/ERCA produces draft nutritional guidelines for renal patients.

PMID- 12073385
TI  - Northwest Kidney Centers.

PMID- 12073386
TI  - New European guidelines for microbiological quality of dialysis fluid: a review.

PMID- 12073387
TI  - Crossing the quality chasm.

PMID- 12073388
TI  - Scope and standards of advanced practice in nephrology nursing.

PMID- 12073389
TI  - Dialysis catheters. How and when to use them.

PMID- 12073390
TI  - The economic impact of vascular access.

PMID- 12073391
TI  - GenoMed research finds ACE inhibitors delay kidney disease.

PMID- 12073392
TI  - Roche licenses Gryphon's synthetic erythropoiesis protein for anemia.

PMID- 12073393
TI  - Aventis, Pfizer develop Exubera to treat type 1 diabetes.

PMID- 12073394
TI  - Kidney & urology foundation aims to increase awareness of disease.

PMID- 12073395
TI  - Despite protests, 10% cut in home dialysis payments still alive.

PMID- 12073396
TI  - Positive attitude. The first step to living long and well with kidney disease.

PMID- 12073397
TI  - From diagnosis to dialysis. Kidney School helps patients cope with kidney
      disease.

PMID- 12073398
TI  - Attitude, answers, and action. Positive outlook overcomes challenges.

PMID- 12073400
TI  - [Not enough physicians in 2020? Chronicle of an unsupported alarm].

PMID- 12073399
TI  - [The use of exit questionnaires, a survey at 7 hospital centers].
AB  - Measuring the satisfaction of hospitalised patients has been mandatory in France
      since 1996. The most common tool for assessing the level of satisfaction is the
      use of self-administered questionnaires given to the patient upon his/her release
      from the hospital. A survey was conducted among seven public hospitals to
      appraise the development and use of such questionnaires, their results and the
      way in which these results are taken into account in order to improve the quality
      of care. The survey's results illustrate that the policy with respect to their
      construction varies between hospitals, without any evaluation of the validity of
      the questionnaires produced. In most cases, the questionnaires are passively
      distributed to the patient at the time of discharge. The response rates are low
      (ranging from 4 to 18%), and the analysis of the collected questionnaires, to the
      extent to which it is done, is not necessarily used to improve the quality of
      care. An appropriate evaluation strategy, one capable of effecting change and
      improving hospital care, still remains to be established in the hospitals which
      participated in the survey.

PMID- 12073401
TI  - [Writing quality of medical prescriptions at the Social Security System of
      Ouagadougou].
AB  - A medical prescription may sometimes include errors which might have a negative
      impact on the patient's health. The objective of this study was to analyse the
      key elements of medical prescriptions given to patients covered by the
      Ouagadougou social security health insurance system. The population of
      practitioners included in the study comprises all of the medical doctors
      practicing in Ouagadougou. The study consisted of a review of all prescriptions
      registered by the family benefits and professional hazards service branches
      dating from January 1st to December 31st 1997. The identification of the doctors
      and patients was satisfactory in more than 97% of the prescriptions. However,
      certain errors were frequent such as the omission of the treatment's duration,
      the medication's dosage, and the form. The oversights observed were comparable to
      those described in the literature. Repeating similar periodic evaluations with a
      systematic feedback relayed to the practitioners will bring about an improvement
      of medical prescriptions.

PMID- 12073402
TI  - [Analysis of preliminary conditions for the implementation of health training
      programs within the framework of humanitarian aid].
AB  - NGOs must be able to ensure the appropriate design and quality of their training
      programmes for health workers implemented in developing countries. It is a
      question of empowering those countries to become more autonomous, and the purpose
      of this study is to identify factors that can improve the sustainable management
      of the population's health through the long-term training of competent health
      workers. A literature review validated by experts distinguished three main
      characteristics necessary for the success of such programmes; relevance,
      feasibility and functionality from an educational perspective. Moreover, in
      addition to the three aforementioned criteria, a fourth transversal attribute was
      noted: sustainability. The objective of the programme designer is to assess the
      presence of these conditions in order to decide whether or not the training
      programme should be implemented.

PMID- 12073404
TI  - [Chronic renal failure in Poitou-Charentes: prevalence, structure adequacy, and
      patient satisfaction].
AB  - The characteristics of the existing cases in the region, the adequacy of the
      structures with respect to the needs, and the satisfaction of patients undergoing
      dialysis have been analysed as part of an ongoing project for the development of
      a Regional Outline for Health Organisation in the Poitou-Charentes region of
      France. A cross-sectional survey was conducted in the haemodialysis units,
      dialysis facilities and patient associations in the region and bordering areas
      where patients were being treated. As of March 31, 2000, the prevalence of
      chronic renal failure was estimated to be 373 people per one million of the
      population. According to the nephrologist, the adequacy of the care structures
      was found to be satisfactory for 82% of the patients. The main reasons for non
      adequacy were first, the lack of intermediate structures between centres and
      outpatient units; second, the patient's refusal to be referred to another
      structure; and finally, other medical, physical and intellectual factors. For 90%
      of patients, their treatment method corresponded to their choice of therapy. The
      lack of a nearby structure was equally recognised as a primary reason for
      dissatisfaction. It should be noted that 42% of the patients under 60 years old
      felt that they were either poorly or very poorly informed of their rights, the
      coverage and the treatment of this illness.

PMID- 12073405
TI  - [Better adaptation of the Tunisian adolescent health care system].
AB  - Classical health indicators are insufficient to account for adolescent health.
      With the majority of young people's health problems being linked to social and
      behavioural factors, the compartmentalised and biomedical approaches to their
      health are inept. Can the totality of adolescents' health needs receive an
      appropriate response in a health care system which articulates itself based upon
      a parceled vision of health? Health professionals seem to experience difficulties
      in situating themselves above the expressed symptom, and therefore become aware
      of the real needs linked to the emotional, familial and educational contexts and
      integrate a global, multi-disciplinary approach to adolescent and young adult
      health into their everyday practice. Their reduced consumption of care is not
      only linked to the fact that adolescents in general enjoy good health, but it is
      also linked to the difficulties of the health care system to recognise their true
      health needs. It thus emphasises the need to develop competencies in the field of
      adolescent health and organise the work in a multi-disciplinary network. In order
      to accomplish this, it is essential that the medical schools and public health
      schools offer a multi-disciplinary approach to adolescent health allowing for
      future health professionals to be able to address fields which are not uniquely
      bio-medically dependent. Furthermore, the regional medical study and university
      centres must evolve to become welcome centers and care centers for adolescents,
      adopting a multi-disciplinary approach going beyond the simple juxtaposition of
      diverse disciplines.

PMID- 12073403
TI  - [The French and English health systems: compared evolution after the mid-1990s].
AB  - In the recent past, the British and French health care systems have both
      undergone significant reforms, enveloped in a state of Urgency, resulting
      primarily in France from the increasing rate of growth in health expenditure and
      in England from malfunctioning procedures such as waiting lists. After describing
      current features of the National Health Service (NHS), this study extracts and
      considers the points of convergence and divergence in the respective policies of
      the two countries: similarities in the choice of priorities, decentralisation of
      decision-making, negotiation between actors at the local level, development of
      the quality concept, and the differences in formulating objectives and involving
      the system's users. The considerations provided here should allow for a better
      understanding of the developments of these respective health policies and their
      future evolution.

PMID- 12073406
TI  - [Mandatory notification of HIV infection. Epidemiologic justifications and
      ethical questioning].
AB  - Since the appearance in May 1999 of the two decrees on the application of the law
      relative to the reinforcement of sanitation quality control established in July
      1998, the disclosure of HIV infection "irregardless of the stage" has become
      mandatory. This is the first time that it is imposed that one must declare a
      serologic diagnosis, that is to say an infection in the asymptomatic stage. The
      sensitive nature of all of the information available on AIDS provides an
      explanation for the numerous contradictory reactions linked to this decision. We
      attempt to organise the arguments brought forth according to two approaches: 1)
      the epidemiological arguments that justify the compilation of the precise data
      thought to be necessary for the follow-up of the disease and for the
      implementation of well-targeted prevention actions; and 2) the ethical
      reservations concerning such an imposed measurement, as well as the questions
      related to anonymity and confidentiality.

PMID- 12073407
TI  - [Refugees, migrants, language barrier: opinion of physicians on translation
      aids].
AB  - When the patient and caregiver do not share a common language, an interpreter is
      not always the best solution, and in any case, one cannot be present for every
      visit, especially in the case of an emergency. According to a questionnaire that
      was sent to all of the physicians who are members of a health care network for
      asylum seekers in the Swiss canton of Vaud (n = 169), it appears that 45% of
      practitioners found a telephone translation service to be a practical solution,
      and 58% would like medical glossaries with phonetic pronunciation and visual
      illustrations made available. With a response rate of 91%, it is estimated that
      these two types of services would be used as often as qualified interpreters, if
      they were made available. Other translating aids are also proposed.

PMID- 12073408
TI  - Compliance of primary care doctors with asthma guidelines and related education
      programs: the employment factor.
AB  - BACKGROUND: Primary care physicians' adherence to accepted asthma guidelines is
      necessary for the proper care of asthma patients. OBJECTIVES: To investigate the
      compliance of primary care physicians with clinical guidelines for asthma
      treatment and their participation in related educational programs, and to
      evaluate the influence of their employment status. METHODS: A questionnaire was
      administered to a random sample of 1,000 primary care practitioners
      (pediatricians and family physicians) in Israel. RESULTS: The response rate was
      64%. Of the physicians who participated, 473 (75%) had read and consulted the
      guidelines but only 192 (29%) had participated in an educational program on
      asthma management in the last 12 months. The younger the responding physician
      (fewer years in practice), the more likely his/her attendance in such a program
      (p < 0.0001). After consulting the guidelines 189 physicians (40%) had modified
      their treatment strategies. Significantly more self-employed than salaried
      physicians had read the guidelines and participated in educational programs;
      physicians who were both self-employed and salaried fell somewhere between these
      groups. This trend was not influenced by the number of years in practice.
      CONCLUSIONS: All primary care physicians should update their knowledge more
      often. The publication of guidelines on asthma must be followed by their proper
      dissemination and utilization. Our study suggests that major efforts should be
      directed at the population of employed physicians.

PMID- 12073409
TI  - Efficacy of atorvastatin in treating high risk patients to reach low density
      lipoprotein-cholesterol goals: the Treat to Target (TTT-Israel) Study.
AB  - BACKGROUND: Hyperlipidemia is a major risk factor for coronary heart disease.
      Reducing low density lipoprotein-cholesterol can significantly reduce the risk of
      CHD, but many patients fail to reach the target LDL-C goals due to low doses of
      statins or low compliance. OBJECTIVES: To treat high risk patients with
      atorvastatin in order to reach LDL-C goals (either primary or secondary
      prevention) of the Israel Atherosclerosis Society. METHODS: In this open-label
      study of 3,276 patients (1,698 of whom were males, 52%), atorvastatin 10 mg was
      given as a first dose, with follow-up and adjustment of the dose every 6 weeks.
      While 1,670 patients did not receive prior hypolipidemic treatment, 1,606 were
      treated with other statins, fibrates or the combination of both. RESULTS: After 6
      weeks of treatment, 70% of the patients who did not receive prior hypolipidemic
      medications and who needed primary prevention reached target LDL-C levels.
      Interestingly, a similar number of patients who received prior hypolipidemic
      treatment (other statins, fibrates or both) and who did not reach the LDL-C
      treatment goals reached the LDL-C goals for primary prevention with atorvastatin.
      Only 34% of all patients who needed secondary prevention reached the ISA LDL-C
      target of 100 mg/dl. Atorvastatin proved to be completely safe, only two patients
      had creatine kinase elevation above 500 U/L, and another six had mild CK
      elevation (< 500 U/L). None of the patients had clinical myopathy, and only one
      had to be withdrawn from the study. CONCLUSION: Atorvastatin is a safe and
      effective drug that enables most patients requiring primary prevention to reach
      LDL-C goal levels, even with a low dose of 10 mg. Patients in need of secondary
      prevention usually require higher doses of statins.

PMID- 12073410
TI  - Effects of platelet membrane glycoprotein polymorphisms on the risk of myocardial
      infarction in young males.
AB  - BACKGROUND: Platelet adhesion and aggregation are mediated by specific platelet
      membrane glycoproteins GPla/IIa, GPlb alpha, and GPIIb/IIIa, and are essential
      steps in thrombus formation and development of acute myocardial infarction.
      OBJECTIVE: To evaluate the risks exerted by each of the following polymorphisms
      in young males with AMI: HPA-1a/b in GPIIIa: 807C/T in GPIa; and HPA-2a/b. VNTR
      and Kozak C/T in GPlb alpha. METHODS: We conducted a case-control study of 100
      young males with first AMI before the age of 53 and 119 healthy controls of
      similar age. All subjects were tested for the above polymorphisms. RESULTS: The
      allele frequencies of each of the platelet polymorphisms were not significantly
      different between the young man with AMI and the controls. Smoking alone was
      associated with a 9.97-fold risk, and the presence of at least one metabolic risk
      factor resulted in a 2.57-fold risk of AMI. CONCLUSION: The platelet
      glycoproteins polymorphisms studied are not an independent risk factor for AMI.

PMID- 12073411
TI  - The effect of donor age on survival after lung transplantation.
AB  - BACKGROUND: Historically, donor age above 55 years has been considered to be a
      relative contraindication for organ transplantation. The shortage of organs for
      transplantation has led to the expansion of the donor pool by accepling older
      donors. OBJECTIVES: To compare the 1 year follow-up in patients after lung
      transplantation from older donors (> 50 years old) and in patients after
      transplantation from younger donors (< or = 50 years). METHODS: The study group
      comprised all adult patients who underwent lung transplantation at the Rabin
      Medical Center between May 1997 and August 2001. Donors were classified into two
      groups according to their age: < or = 50 years (n = 20) and > 50 years (n = 9).
      Survival, number and total days of hospitalization, development of bronchiolitis
      obliterans syndrome, and pulmonary function tests, were examined 1 year after
      transplantation. RESULTS: We performed 29 lung transplantations in our center
      during the observed period. Donor age had no statistically significant impact on
      1 year survival after lung transplantation. There was no statistically
      significant effect on lung function parameters, the incidence of hospitalization
      or the incidence of bronchiolitis obliterans between both donor age groups at 1
      year after transplantation. CONCLUSIONS: Donor age did not influence survival or
      important secondary end-points 1 year after lung transplantation By liberalizing
      donor criteria of age up to 65 years, we can expand the donor pool, while
      assessing other possible mechanisms to increase donor availability.

PMID- 12073412
TI  - First experience with the home-care management system for respiratory patients in
      Israel.
AB  - BACKGROUND: Ventilator-dependent patients represent an increasing clinical
      logistic and economic burden. An alternative solution might be monitored home
      care with high-tech ventilatory support systems. OBJECTIVES: To explore the
      implications of such home care management, such as its impact on quality of life
      and its cost-effectiveness, and to assess the practical feasibility of this mode
      of home care in Israel. METHODS: We surveyed 25 partly or fully home-ventilated
      patients (17 males and 8 females), average age 37.6 years (range 1-72), who were
      treated through a home care provider during a 2 year period. RESULTS: Most
      patients (n = 18) had a neuromuscular respiratory disorder. The average hospital
      stay of these patients prior to entry into the home care program was 181.2
      days/per patient. The average home care duration was 404.9 days/per patient
      (range 60-971) with a low hospitalization rate of 3.3 +/- 6.5 days/per patient.
      The monthly expenditure for home care of these patients was one-third that of the
      hospital stay cost ($3.546.9 vs. $11.000, per patient respectively). The patients
      reported better quality of life in the home care environment, as assessed by the
      Sickness impact Profile questionnaire. CONCLUSIONS: Home ventilation of patients
      in Israel by home care providers is a practical and attractive treatment modality
      in terms of economic benefits and quality of life.

PMID- 12073413
TI  - Foucher's first dorsal metacarpal artery flap for thumb reconstruction:
      evaluation of 21 cases.
AB  - BACKGROUND: Coverage of part of a soft tissue defect in the thumb, without bone
      shortening and without long-lasting immobilization in an inappropriate position
      leading to stiffness, is difficult to achieve OBJECTIVES: To report our
      experience using Foucher's modification of the first dorsal metacarpal artery
      flap for thumb reconstruction in 21 cases. METHODS: Foucher's flap is based on
      the neurovascular structures of the first dorsal metacarpal artery flap and
      radial nerve-sensitive branches on the dorsum of the second metacarpal and
      proximal phalanx. The cause of injury was work-related in all 21 cases. The
      patients mean age was 37 (range 17-68 years), and mean follow-up was 19 months
      (range 12-31). Emergency surgery was performed in 13 patients with a time delay
      after injury of 4-12 hours. The minimum defect was 12 x 18 mm and the maximum 20
      x 40 mm. Pedicular length was 55-95 mm. A skin bridge was left intact in 16
      cases. In two cases of early postoperative venous congestion and flap loss, a
      cross-finger flap was performed as a salvage procedure. RESULTS: Subjective
      satisfaction score was 8.37/10 (range 4-10); cold intolerance was experienced in
      60% and dysesthesia in 33%. All except one patient are able to use their thumb in
      daily activity. Loss of mobility in the proximal interphalangeal joint of the
      index finger was less than 20 degrees. Semmes-Weinstein sensitivity evaluation
      score was 3.61-4.31 on the flap and 0-6.65 on the donor site. Two-point
      discrimination was 10.8 mm (range 8-20). Grip strength was reduced by 15%
      compared to the unaffected hand (hand dominance was not taken into
      consideration). Rehabilitation was not consistent as almost all the patients were
      living in another location. CONCLUSIONS: First DMCA pedicle flap is a successful
      thumb reconstruction method, especially in patients not disturbed by its cosmetic
      appearance.

PMID- 12073414
TI  - The role of family physicians in increasing annual fecal occult blood test
      screening coverage: a prospective intervention study.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of cancer mortality in
      israel. Unfortunately, compliance with annual fecal occult blood testing is very
      low. OBJECTIVE: To assess the effectiveness of interventions to increase FOBT
      screening in primary care clinics in Israel. METHODS: A prospective, randomized
      study included all 50-75 year old enrollees of six family physicians in two
      primary care clinics. The register of two physicians, one from each clinic, was
      allocated to one of three groups. Two FOBT reminder strategies were tested: a
      physician reminder (753 patients), and a patient reminder that was either a phone
      call (312 patients) or a letter (337 patients). The control group (913 patients)
      of physicians continued administering their regular level of care. The main
      outcome measure was the percentage of patients undergoing FOBT screening in each
      study arm at the conclusion of the one year study period. RESULTS: In the
      intervention groups 14.3% (201/1,402) were screened using the FOBT over the
      course of the study year. Using an intent-to-screen analysis, the screening rate
      in the physician and patient reminder groups was significantly higher than in the
      control group (16.5 and 11.9%, vs. 1.2% respectively, P < 0.0001). Phone
      reminders were significantly more effective than letters (14.7 vs. 9.2%, P =
      0.01). CONCLUSIONS: Various reminder systems for FOBT are beneficial, especially
      those centered around the family physician. Further research should focus on this
      area, in conjunction with other novel approaches.

PMID- 12073415
TI  - Reduction in resting metabolic rate and ratio of plasma leptin to urinary nitric
      oxide: influence on obesity-related hypertension.
AB  - BACKGROUND: Multiple factors are involved in the pathogenesis of hypertension in
      the obese individual OBJECTIVE: To evaluate the role of a decrease in
      sympathetically mediated thermogenesis and the effect of the correlation between
      the plasma leptin and daily urinary nitric oxide levels on obesity-related
      hypertension. METHODS: We evaluated three groups: 25 obese hypertensive patients
      (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic
      blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50
      mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76,
      SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive
      subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5,
      MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin
      (radio-immunoassay), norepinephrine (high performance liquid chromatography) in
      all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction
      diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations
      were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx
      (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese
      normotensives, and in 19 obese hypertensives versus 11 obese normotensives,
      respectively. RESULTS: Obese hypertensive patients had significantly higher basal
      RMR and plasma NE levels insulin levels were lower in the lean group, with no
      difference between the hypertensive and normotensive obese groups. At weeks 6 and
      14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to
      values of normotensive subjects. MAP normalized but remained significantly higher
      than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were
      significantly higher in the obese hypertensive compared to the obese normotensive
      patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and
      plasma NE and insulin. Obese hypertensive patients excreted less urinary NO
      metabolites. A strong correlation was found between MAP and the leptin/UNOx
      ratio. CONCLUSIONS: A reduction in sympathetically mediated thermogenesis, as
      reflected by RMR, results in normalization of obesity-related hypertension. In
      contrast, insulin does not seem to play a major role in the pathogenesis of
      hypertension associated with obesity. Increased leptin levels in conjunction with
      decreased NO production in the presence of enhanced sympathetic activity may
      contribute to blood pressure elevation in the obese.

PMID- 12073416
TI  - Clinical implications of small bowel diverticula.
AB  - BACKGROUND: Small bowel diverticula are usually asymptomatic and rare. Their
      importance is based on the fact that they carry the risk of serious
      complications. OBJECTIVE: To study the implications and the therapeutic approach
      regarding small bowel diverticulosis. METHODS: The medical records of 54 patients
      with diverticular disease of the small bowel, including Meckel's and duodenum
      diverticula, were retrospectively reviewed. The mean age of the 32 male and 22
      female patients was 53.2 years. RESULTS: Diverticula were found in the duodenum
      in 11 cases, in the jejunum and ileum in 21 cases, and with Meckel's diverticula
      in 22 cases. In 24% of the patients the diverticula were multiple. The most
      common clinical symptom was abdominal pain, in 44.4%. Most of the duodenum
      diverticula were asymptomatic; 47.6% of the patients with diverticular disease
      located in the jejunum and ileum presented with chronic symptoms. The overall
      diagnostic rate for symptomatic diverticula before surgery was 52.7%; in 33.3%
      diverticula were found incidentally during other diagnostic or therapeutic
      procedures. Forty-one patients were managed surgically. 15 patients were operated
      on urgently because of infection or rupture, 4 patients for bleeding, 5 patients
      for intestinal obstruction, and one patient for jaundice. CONCLUSIONS: The
      incidence of asymptomatic small bowel diverticula is difficult to ascertain.
      Patients with Meckel's and duodenal diverticula are usually asymptomatic, while
      the majority of jejunal and ileal diverticula patients present with chronic
      symptoms. The pre-operative diagnostic rate is higher for duodenal diverticula.
      Small bowel diverticula do not require surgical treatment unless refractory
      symptoms or complications occur.

PMID- 12073417
TI  - Avascular necrosis and related complications following healed osteoporotic
      intertrochanteric fractures.
AB  - BACKGROUND: Femoral hip fractures are a common occurrence in the elderly. Of the
      various fracture patterns, intertrochanteric injuries have the lowest rate of
      complications. Case reports of ensuing subcapital fracture have all been linked
      to incorrect placement of fixation devices or to osteomyelitis, white cases of
      avascular necrosis have only been reported rarely in the literature and are
      considered to occur at the rare rate of 0.8%. OBJECTIVES: To check the incidence
      and outcome of AVN in intertrochanteric hip fractures. METHODS AND RESULTS: In a
      retrospective analysis of patients who had surgical treatment for
      intertrochanteric fractures. 10 patients (0.5%) underwent dynamic hip screw
      fixation for intertrochanteric fractures and subsequently developed painful AVN
      as their primary presentation. Three of these patients were also found to have
      subcapital fractures. On revision of the primary fixation no fault was found with
      nail placement. CONCLUSIONS: The reported rate of AVN may be understated since
      many patients have limiting factors that prevent them from consulting a physician
      when in pain, and one-third of these patients die within 2 years. Therefore, we
      suggest that hip pain following fixation of an intertrochanteric fracture should
      prompt the clinician to consider the rare possibility of AVN or subcapital
      fracture.

PMID- 12073418
TI  - Genetic dissection of common diseases.
AB  - The complex genetic nature of many common diseases makes the identification of
      the genes that predispose to these ailments a difficult task. In this review we
      discuss the elements that contribute to the complexity of polygenic diseases and
      describe an experimental strategy for disease-related gene discovery that
      attempts to overcome these factors. This strategy involves a population-based
      case-control paradigm and makes use of a highly informative, homogeneous founder
      population, many of whose members presently reside in Israel. The properties of
      single nucleotide polymorphisms, which are presently the markers of choice, are
      discussed, and the technologies that are currently available for SNP genotyping
      are briefly presented.

PMID- 12073419
TI  - Early-onset type 2 diabetes in Mexico.
AB  - This review summarizes the clinical, metabolic and genetic characteristics of
      early-onset type 2 diabetes in Mexico. Early-onset type 2 diabetes is both a
      clinical challenge and a public health problem. It is calculated that almost
      300,000 Mexican diabetics are diagnosed between the ages of 20 and 40. The large
      Mexican family structure and the high prevalence of the disease provide a unique
      opportunity to identify the genes and the metabolic abnormalities involved in
      this form of the disease. In a hospital-based population, our group found that
      insulin deficiency was the main defect in this form of diabetes. Mutations in the
      NHF-1 alpha or HNF-4 alpha genes or autoimmunity to the beta cell were found in a
      small proportion of cases, leaving unexplained the majority of cases. Also
      discussed are the epidemiologic and therapeutic implications of early-onset type
      2 diabetes, and the possible role of genetic testing for prevention.

PMID- 12073420
TI  - The chronic cholestasis engima in adults.

PMID- 12073421
TI  - Do pediatricians use asthma management guidelines, and if not, why not?

PMID- 12073422
TI  - Statins: an effective anti-atherosclerosis therapy.

PMID- 12073423
TI  - Are platelet membrane glycoprotein polymorphisms predictive of arterial
      thrombosis?

PMID- 12073424
TI  - The quandary of home-care respiratory management.

PMID- 12073425
TI  - Diffuse alveolar hemorrhage in autoimmune diseases.

PMID- 12073426
TI  - Syphilitic gumma and tuberculosis: an unusual combination in AIDS.

PMID- 12073427
TI  - Pulmonary alveolar hemorrhage in a patient with ulcerative colitis and primary
      sclerosing cholangitis.

PMID- 12073428
TI  - Schnitzler syndrome: chronic urticaria, fever and immunoglobulin M monoclonal
      gammopathy.

PMID- 12073429
TI  - Treatment of cavernous sinus thrombosis.

PMID- 12073430
TI  - Diffuse alveolar hemorrhage in systemic lupus erythematosus.

PMID- 12073431
TI  - Coley's toxin: historical perspective.

PMID- 12073432
TI  - Screening for congenital toxoplasmosis.

PMID- 12073434
TI  - Specific clinical constellations might mask the genetic over-sensitivity to
      warfarin.

PMID- 12073433
TI  - Experience in an emergency department after the Marmara earthquake.

PMID- 12073435
TI  - Labeling DNA breaks in situ by Klenow enzyme.

PMID- 12073436
TI  - In situ nick translation at the electron microscopic level.

PMID- 12073437
TI  - In situ DNA ligation as a method for labeling apoptotic cells in tissue sections.
      An overview.

PMID- 12073438
TI  - Detection of specific double-strand DNA breaks and apoptosis in situ using T4 DNA
      ligase.

PMID- 12073439
TI  - In situ detection of double-strand DNA breaks with terminal 5'OH groups.

PMID- 12073441
TI  - The comet assay. An overview of techniques.

PMID- 12073440
TI  - The comet assay. Principles, applications, and limitations.

PMID- 12073443
TI  - Application of FISH to detect DNA damage. DNA breakage detection-FISH (DBD-FISH).

PMID- 12073442
TI  - Ultrasensitive detection of DNA damage by the combination of the comet and TUNEL
      assays.

PMID- 12073444
TI  - TUNEL assay. An overview of techniques.

PMID- 12073445
TI  - Simultaneous in situ detection of DNA fragmentation and RNA/DNA oxidative damage
      using TUNEL assay and immunohistochemical labeling for 8-hydroxy-2'
      deoxyguanosine (8-OHdG).

PMID- 12073446
TI  - The in situ detection of apurinic/apyrimidinic sites and DNA breaks bearing
      extension blocking termini.

PMID- 12073447
TI  - Markers of poly (ADP-ribose) polymerase activity as correlates of DNA damage.

PMID- 12073448
TI  - Ultrasound imaging of apoptosis. DNA-damage effects visualized.

PMID- 12073449
TI  - p53 induction as an indicator of DNA damage.

PMID- 12073450
TI  - Detection of caspases activation in situ by fluorochrome-labeled inhibitors of
      caspases (FLICA).

PMID- 12073451
TI  - Labeling DNA damage with terminal transferase. Applicability, specificity, and
      limitations.

PMID- 12073452
TI  - Electron microscopic detection of DNA damage labeled by TUNEL.

PMID- 12073453
TI  - Quantitative differentiation of both free 3' OH and 5' OH DNA ends using terminal
      transferase-based labeling combined with transmission electron microscopy.

PMID- 12073454
TI  - Determination of three-dimensional distribution of apoptotic DNA damage by
      combination of TUNEL and quick-freezing and deep-etching techniques.

PMID- 12073455
TI  - In situ detection of DNA strand breaks in analysis of apoptosis by flow- and
      laser-scanning cytometry.

PMID- 12073456
TI  - DNA damage detection using DNA polymerase I or its Klenow fragment.
      Applicability, specificity, limitations.

PMID- 12073457
TI  - Accountability stops here.
AB  - Did you know how hard being a health care trustee was going to be when you signed
      on for the job? Just how broad is the scope of your responsibilities and how can
      you learn how to meet them effectively?

PMID- 12073458
TI  - Finding the perfect fit. Is your board chair the right person in the right place?
AB  - Just as the board's role in a health care organization has expanded, so, too, has
      the board chair's. Since a board can only be as effective as its chair, choosing
      the best person for the job is critical. These considerations and guidelines
      should ease the burden.

PMID- 12073459
TI  - Succession planning: charting a course for the future.
AB  - Whether your CEO's departure has been long anticipated or sudden, do you know who
      will succeed him/her and what the next step will be? For the health of your
      organization, community, and employees, it's a good idea to have a succession
      plan in place long before you need to implement it.

PMID- 12073460
TI  - Personal best: coaches help CEOs reach new heights.

PMID- 12073461
TI  - Are you ready for HIPAA? A checklist for boards.

PMID- 12073462
TI  - Hospitals feeling 'niched to death'.

PMID- 12073463
TI  - Back to basics 2. Why do health care trustees need D&O liability insurance?

PMID- 12073464
TI  - A quick fix for a cosmetic emergency.

PMID- 12073465
TI  - How to eliminate no-shows, cancellations, and accounts receivable.

PMID- 12073466
TI  - Firewalls. Internet security for your PC, peace of mind for you.

PMID- 12073467
TI  - A look at air abrasion systems.

PMID- 12073468
TI  - Laminar technique.

PMID- 12073469
TI  - Principles.

PMID- 12073470
TI  - Amalgam revisited.

PMID- 12073471
TI  - OSHA issues hazard bulletin for exposure to beryllium in dental labs.

PMID- 12073474
TI  - Pediatric patient management techniques: a new look.

PMID- 12073475
TI  - Active decay and fluoride varnish.

PMID- 12073476
TI  - Smallpox vaccinations revisited?

PMID- 12073478
TI  - Meeting patient demand with computer-generated veneers.

PMID- 12073477
TI  - Save a life in 3 minutes.

PMID- 12073479
TI  - Digital radiographic imaging in dental practice.

PMID- 12073480
TI  - Computerized shade selection and the complex Class IV composite.
AB  - By utilizing digital shade mapping, a stratified composite technique, and the
      proper composite system, the dental practitioner stands a greater chance of
      meeting patient expectations. In the case presented, the use of the Clear-Match
      system helped simplify shade selection, which is the greatest variable in success
      of anterior composite restorations.

PMID- 12073481
TI  - Top ten systems for taking the stress out of endodontics.

PMID- 12073482
TI  - Simple, predictable, and stress-free elective anterior dentistry. Build a
      successful outcome into every case.

PMID- 12073483
TI  - An improved technique for restoring a challenging treatment zone.

PMID- 12073485
TI  - Direct fiber-reinforced composite bridges.

PMID- 12073484
TI  - Removable prosthodontic therapy and xerostomia. Treatment considerations.
AB  - Successful management of complete and removable partial dentures is complicated
      by a reduction in saliva. Dental practitioners should be aware of the signs and
      symptoms of xerostomia, available diagnostic procedures, likely etiologies,
      expected sequelae, and appropriate therapeutic regimens. Effective evaluation and
      appropriate treatment will promote acceptable levels of comfort and function.
      Over-the-counter (Figure 12) and prescription medications may be needed to
      improve the clinical situation.

PMID- 12073486
TI  - Utilizing the concept of the golden proportion.

PMID- 12073487
TI  - A new year for Emily.

PMID- 12073488
TI  - Concerned about being disciplined? You have the right to union representation.

PMID- 12073489
TI  - Caring for the community.

PMID- 12073491
TI  - Building reliability into your digital telemetry system.

PMID- 12073490
TI  - Gaining with integration. Three healthcare organizations use integrated financial
      clinical systems to achieve ROI, process improvement and patient care objectives.

PMID- 12073492
TI  - HL7--what you need to know.

PMID- 12073493
TI  - What a difference a day makes. A Houston health plan customizes its care
      management technology to eliminate unnecessary inpatient days.

PMID- 12073494
TI  - [Experiences with follow-up investigations of oral vaccination campaigns against
      rabies in foxes in Saxony with special emphasis on a standardised serology].
AB  - An 8-year experience with organisation and standardisation of follow-up
      investigations within oral vaccination campaigns against rabies in foxes (OVF) in
      Saxony is summarised. With respect to OVF, the number of diagnostic tests
      performed during the years 1992-2000 on foxes amounts to a total of 52,226
      Fluorescence antibody-(FAT), 7,551 marker-(TC) and 11,645 serological tests. The
      mean bait-uptake and the mean immunisation rate in foxes ranged between 78-86%
      and 60-89%, respectively. Based on the seroconversion rates of the years 1997
      2000 observed in vaccination areas and in areas where vaccination was already
      finished, experience with a standardised serology under routine conditions is
      presented and discussed. Furthermore, recommendations concerning organisation and
      logistics of sampling are given.

PMID- 12073495
TI  - Leukopenia and thrombocytopenia in pigs after infection with bovine viral
      diarrhoea virus-2 (BVDV-2).
AB  - The aim of this study was to investigate whether bovine viral diarrhoea virus-2
      (BVDV-2) is pathogenic for pigs, which organs become infected and whether or to
      which extent the virus is excreted into the environment. Ten pigs were observed
      for clinical reactions after infection with a BVDV-2 strain, that has been shown
      to be pathogenic in calves under experimental conditions. Samples were taken to
      monitor thrombocyte and leukocyte counts as well as antibody development. Post
      mortem examinations were performed at 7, 11 and 27 days after infection. Tissue
      samples were collected for virus isolation, histological and immunohistological
      examination. All ten pigs became infected and BVDV could be re-isolated from the
      lymphocytes, the plasma and different lymphatic organs. The infection passed
      clinically inapparent, apart from a slight increase in body temperature in some
      animals. Some animals developed a slight leukopenia and/or thrombocytopenia.
      There were no macroscopic or histological lesions observed that could
      specifically be related to the inoculation of BVDV-2. With respect to all
      parameters studied, the infection and the consequences thereof were clearly less
      pronounced in pigs as compared to cattle, the natural host. Our results indicate,
      that pigs infected with BVDV-2 might develop antibodies that cross-react in tests
      for antibodies against classical swine fever virus.

PMID- 12073496
TI  - [Establishment and evaluation of an ELISA for the detection of antibodies in milk
      against Mycobacterium avium subspecies paratuberculosis].
AB  - Mycobacterium avium ssp. paratuberculosis (M. paratuberculosis) is the
      etiological agent of paratuberculosis (Johne's Disease), a chronic granulomatous
      enteritis of ruminants occurring worldwide with increasing frequency and leading
      to growing economic losses. Continuous surveillance of dairy farms would be
      advisable, particularly with respect to the increasing economic importance of
      paratuberculosis and the high tenacity of the pathogen, which can persist in the
      environment for many months. So far, such measures have not been taken as the
      cost-intensive collection of serum samples would have been required. Based on
      these considerations, it was the aim of this study to evaluate an economically
      viable diagnostic method for antibody detection using milk samples. This
      objective was reached by establishing a milk-ELISA. A commercially available test
      (Svanovir-ELISA by Svanova, Sweden) was chosen, because this ELISA has an
      excellent specificity with respect to cultural examination of the ileocaecal
      lymph node ("Gold-Standard"). The Svanovir-ELISA could be successfully adapted
      for testing milk for antibodies against M. paratuberculosis. The milk is skimmed
      by centrifugation and is diluted 1:10 for testing. The inter-assay-variation was
      17%. A comparative antibody analysis done in parallel with milk and serum samples
      from 601 dairy cows using the Svanovir-ELISA showed a significant correlation
      between the results obtained with both methods. The optimal "cut-off" for the
      milk-ELISA of 46 EUMS (> 46 EUMS = positive) resulting in a specificity of 94.6%
      and a sensitivity of 60.9% was confirmed by receiver-operator characteristics
      (ROC) analysis. In the meantime the Svanovir-ELISA has been licensed for use with
      milk samples in Germany.

PMID- 12073497
TI  - [Preclinical studies for the use of the platelet function analyser PFA-100 with
      the collagen/ADP cartridge in dogs].
AB  - In this study, the following three aspects of platelet function analyser were
      investigated in dogs, using a collagen/ADP cartridge: precision, influence of the
      cartridge batch and of the sample storage time. Closure time and total volume of
      blood flow until closure of the capillary were measured. Based on several series
      of 5 repeated measurements mean coefficients of variation were 5% (3-6%; closure
      time) or 3% (1-5%; total volume). Neither closure time, nor total volume showed
      significant differences (p > 0.05) when comparing the results of 6 different
      batches of the collagen/ADP cartridge. Closure time (p = 0.0211, analysis of
      variance) and total volume (p = 0.0310) were significantly influenced by storage
      time, based on the sample material of 6 healthy dogs which was stored for 24
      hours. Shortening of the closure time and decrease of the total volume observed
      in the time interval 1-2 hours after blood collection was followed by a
      significant prolongation of closure time and increase of the total volume (p <
      0.05) starting 8 hours after blood collection. This study shows sufficient
      reproducibility which is not affected by reagent batch number. The results of the
      studies on storage indicated nearly identical recommendations for storage time
      before measurement of canine (0.5-2 hours) and human (0.5-3 hours) sample
      material.

PMID- 12073498
TI  - [Reactions of young cattle from a suckler herd to shorthaul transport by road-
      repeated investigations before and after permanent separation of young cattle
      from their dams. Plasma cortisol, biochemical, hematological variables, minerals
      and heart rate].
AB  - On 8 female young cattle from a suckler herd blood sampling (V. jugularis) and
      body temperature measurements (RT) before (U1; U11) and after transport (U2; U21)
      and on the next day (U3; U31) were combined with long term heart rate (HF)
      recording before (U1 to U3) and 23 d later (16 till 18 days) after permanent
      separation of the young cattle from their dams (U11 to U31). After weaning plasma
      concentrations of urea and Ca were greater and that of creatinine was smaller in
      young cattle than before. Characteristic heart rate values before transport and
      those of the 24-h-recordings were significantly smaller after weaning. Plasma
      cortisol concentrations before transport were increased (U1: 40.3 +/- 10.4; U11:
      16.8 +/- 3.9 nmol/l) and they were only less further elevated after transport
      (U2: 52.6 +/- 19.5; U21: 33.4 +/- 18.3 nmol/l). On the next day cortisol values
      (U3: 33.3 +/- 23.7; U31: 12.5 +/- 5.8 nmol/l) were significantly smaller than the
      initial values. HF increased significantly with loading and with the start of
      transport comparing the characteristic heart rate values of the other periods of
      the transport process and the initial values before the transport and of the 24-h
      recording after the transport process. Significant mean differences before and
      after transport could be found for body temperature, creatinine, urea,
      hematocrit, pO2, Ca, Mg, and Fe. Separation of young cattle from their dams had
      effects on some variables before transport but did not change the reaction of the
      animals to transport. Results show the significance of the events and their
      effects on the animals before transport and their timely relationship for the
      reactions of the animals during and after transport and the markedly
      interindividual variation of the reactivity of the young cattle.

PMID- 12073499
TI  - [The stability of progesterone in feces of different wild animal species kept in
      a zoological garden].
AB  - Methodical investigations were carried out to monitor especially in what respect
      external factors (dry mass of faeces, time point of freezing, duration of storage
      of the frozen samples, multiple defrosting of the samples) influence the
      progesterone concentration of the faeces of several wild animal species (Baringo
      giraffe, Black rhinoceros, Dama gazelle, Mountain goat) living in a zoological
      garden. With reference to one animal species the dry mass of the faeces showed
      only small variations. Therefore, it is possible to estimate comparable
      progesterone levels in several faecal samples of the same animal species without
      drying the samples. In all cases the progesterone concentration was increased
      after 24 and 48 hour storage of the faecal samples at room temperature compared
      with samples frozen directly (significant differences for giraffes and
      rhinoceroses). Samples of rhinoceroses and gazelles showed no significant changes
      of their progesterone concentration after a long time of storage (one and three
      months) in the freezing state (-20 degrees C). On the other hand, in faeces of
      giraffes with high progesterone levels a significant decrease of the initial
      level was pointed out. In comparison of single and multiple defrosting of the
      faecal samples, the latter caused a decrease of the progesterone concentration of
      the faeces of all animal species investigated (significant differences for
      rhinoceroses and gazelles).

PMID- 12073500
TI  - [Concealed local recurrence after breast-conserving treatment].
AB  - Three women, aged 43, 50 and 49 years, presented themselves with subjective
      changes of the breast 8, 17 and 16 years respectively after breast conserving
      surgery. Mammography and ultrasonography revealed no indications for a local
      recurrence, but in the first patient Technetium-99m-sestamibi (MIBI)
      scintimammography did. All three patients underwent mammary ablation,
      radiotherapy and hyperthermia. The first one died from metastatic disease. The
      traditional way to diagnose breast abnormalities is inspection, palpation,
      mammography combined with ultrasonography and MRI. When local breast cancer
      recurrence is suspected following breast-conserving treatment, these
      investigations are often inconclusive. Mammography and ultrasonography in
      particular give many false-negative results. It is therefore important to send
      these patients to an experienced physician and not to be too reserved in
      performing a blind biopsy. Performing an MIBI scintimammography can be helpful in
      differentiating between malignant and benign lesions of the breast.

PMID- 12073501
TI  - [Population screening for breast cancer: between euphoria and scepticism].
AB  - Forty years after the first mammograms were made, doubts are cast on the
      effectiveness of population screening for breast cancer. Disease-specific and
      overall mortality appear to have diminished, but any real effect is small.
      Proponents of breast cancer screening point at the possibility of saving lives
      and at the obligation to do so, whereas opponents emphasise that the screening
      may do more harm than good and that the large funds involved might be better
      spent in other health care areas. If the experts cannot decide on the
      effectiveness, simply leaving the choice of whether or not to take part up to
      citizens offers no solution. These complex health care matters require complex
      answers, which have to be found before any population screening for cancer of
      prostate, colon or lung can be implemented.

PMID- 12073502
TI  - [The benefit of population screening for breast cancer; an advisory report from
      the Health Council of the Netherlands].
AB  - A recent Cochrane review does not nullify the evidence supporting the practice of
      mammographic population screening for breast cancer for women aged 50 years and
      over. Thus concludes the Health Council of the Netherlands in an advisory report
      to the Dutch Government. A central feature of the Cochrane review is the
      conclusion that breast-cancer mortality is an unreliable outcome that is biased
      in favour of screening. The Health Council finds this conclusion too extreme and
      does not support the view that breast-cancer mortality must be replaced by
      overall mortality as an outcome. The Health Council does agree with the view that
      the use of disease-specific mortality as the only endpoint renders cancer
      screening trials subject to bias. Therefore, careful attention should be paid to
      total cancer mortality, other important causes of death, and overall mortality.

PMID- 12073503
TI  - [The biased information given to women about population screening for breast
      cancer makes a well considered informed choice to participate unlikely].
AB  - The 'Wet op de Geneeskundige Behandelingsovereenkomst' (Act on Agreement
      Concerning Medical Treatment) requires that patients are clearly informed about
      'the risks and consequences that can be expected from an intended treatment or
      investigation'. The information received by women aged 50-74 years when invited
      for a biannual investigation for breast cancer does not satisfy the requirements:
      the available knowledge is presented too favourably and it is therefore not
      possible to make a well-considered informed choice to participate. For example,
      in the group to be screened, 4000 cases of breast cancer are diagnosed each year,
      yet in the information leaflet a figure of 9000 is stated, the number for all age
      categories. Furthermore, these 9000 cases include 1500 cases detected only as a
      result of screening. In the information leaflet no mention is made of the fact
      that 1 in 5 women will die despite screening and the risk of interval carcinomas
      is not examined; 40% of malignant mammary tumours are still found outside of the
      screening programme.

PMID- 12073504
TI  - [Clear-cut beneficial effect of breast cancer screening on the trend in breast
      conserving surgery].
AB  - Since the introduction of mammographic screening, controversies have emerged
      concerning its effect on mortality as well as on the management of breast cancer.
      A Dutch population-based study demonstrates a significant difference between
      screening-detected breast cancers and non-screening-detected breast cancers in
      terms of smaller tumour size, more favourable nodal status and a 14% increase
      (difference between percentages) in breast-conserving surgery in favour of the
      screening-detected group. However, since no overall increase in the rate of
      breast-conserving therapy was found, the authors concluded that the impact of
      screening on surgical management was limited. An alternative explanation is that
      during the 1990s, the indications for breast-conserving surgery have become more
      restrictive in terms of tumour-free margins. Other investigators have
      demonstrated similar increases in the rate of breast-conserving surgery in
      screening-detected breast cancer patients. Although the debate on mammographic
      screening has definitely not reached its conclusion, Swedish data available
      clearly demonstrate a decrease in breast cancer mortality (21%) due to
      mammographic screening, which is contrary to recent criticism.

PMID- 12073505
TI  - [The effect of treatment delay on the prognosis of breast cancer patients].
AB  - The central issue of waiting lists is health loss that may result from treatment
      delay. As no randomised controlled trials exist, all studies on the relationship
      between delay and outcome are subject to bias, the extent of which depends on the
      mechanisms that cause delay. From published observational data, the deleterious
      effect of delay on prognosis was estimated to be nearly 2% in 5-year mortality
      per month of treatment delay in breast cancer. A modelling approach suggests a
      more limited delay-loss effect of around 1% per month of delay, equalling a loss
      of life expectancy of around 3 months. These figures support the belief that
      treatment of breast cancer should not be delayed further than a period of 3
      weeks, striking a reasonable balance between therapeutic 'surprise attack' of the
      patient and unnecessary delay. In the presence of waiting lists, prioritization
      of patient treatment should be guided by the aim to minimize health loss, based
      on the relationship between treatment delay and health loss. Such considerations
      are valid not only for breast cancer patients, but for all patients in whom delay
      may result in serious health loss.

PMID- 12073507
TI  - [The pretentions and achievements of cancer screening, in particular breast
      cancer screening].
AB  - The 'Vereniging Nederlands Tijdschrift voor Geneeskunde' (Dutch Journal of
      Medicine Association) recently held a conference about the doubts expressed in
      recent publications concerning the value of cancer screening and breast-cancer
      screening in particular. In this the discussion mainly focused on whether disease
      specific mortality or overall mortality should be taken as an endpoint in the
      evaluation of the screening procedure. In a recent advisory report, the Health
      Council of the Netherlands stated that the present form of breast cancer
      screening ought to be continued in the Netherlands for the time being. However,
      during the conference it was emphasized that cancer screening must be viewed as a
      highly complex system. Therefore, it is impossible to measure the effects of
      screening by considering just one end-point, such as cancer-specific mortality.
      The opinion was also expressed that with the introduction of new forms of cancer
      screening (e.g. colon or prostate-cancer screening), experience should first of
      all be gained with the small-scale screening of persons with an elevated risk.
      This is a task in which the government should lead the way. Furthermore, the
      government will also need to regulate the enthusiasm that can be expected for
      various types of secondary preventative diagnostics offered on the free market,
      including cancer screening. Another important aspect of cancer screening is
      ensuring that the general public are thoroughly and carefully informed about the
      pros and cons of cancer screening. The public must know that although cancer
      screening can save lives, it also causes harm. People scarcely realise that
      screening may more often involve a loss of carefree years of life than a small
      chance of living longer.

PMID- 12073506
TI  - [The scientific basis for population screening for breast cancer in the
      Netherlands].
AB  - A recent Cochrane review stated that there was a lack of evidence for a decrease
      in mortality as a result of population breast-cancer screening. The principal
      data were drawn from five Swedish randomized controlled trials and one Canadian
      trial. However, the studies cannot be so easily combined because there were
      important differences in the attendance rate, detection rate, technical quality,
      referral rate, clinical baseline situation and screening interval. For example,
      in one of the studies the women from the control arm underwent an annual clinical
      palpation carried out by a trained nurse or physician, which could have led to an
      underestimation of the screening effect. Further breast-cancer mortality might
      not be a good outcome measure because this was not reliably determined; only
      total mortality was to be observed. This is clinically and methodologically
      incorrect because breast-cancer mortality was meticulously studied, documented
      and validated. In the Cochrane review it is suggested that the randomisation was
      inadequate, but evidence for this was not supplied. The discussion about age
      differences as a marker for incorrect randomisation is out of date and has been
      revealed to be unjust. It seems likely that an important part of the decreasing
      trend in breast-cancer mortality in several countries (including the Netherlands)
      is due to screening programmes. However, the evaluation of breast-cancer
      mortality over the next five years is crucial, if greater certainty is to be
      gained about this.

PMID- 12073508
TI  - [The meaning of medical information to judge employee disability].

PMID- 12073509
TI  - [The meaning of medical information to judge employee disability].

PMID- 12073511
TI  - [Karl Landsteiner (1868-1943) and the specificities of serologic reactions, a
      hundred years ago and now].

PMID- 12073510
TI  - [Hallucinations caused by paroxetine in combined usage of levodopa-carbidopa].

PMID- 12073513
TI  - First person. Empty promises.

PMID- 12073512
TI  - Human resources. Rallying the troops.
AB  - The government's plans for the NHS will not be achieved simply through meeting
      its targets for staffing. More attention should be given to retention and a
      fairer pay system. The introduction of new roles and skill mix will be the
      biggest test of the human resources agenda. Success is more likely to come from
      developing the roles of current health professionals than from introducing new
      types of workers.

PMID- 12073514
TI  - Discharge planning. Armchair fan.
AB  - The establishment of a discharge lounge is believed to have reduced pressure on
      beds in the wards. All adult wards refer patients to the lounge, where the
      average wait is two hours. The establishment of the lounge has reduced delays for
      ambulance crews who no longer have to collect patients from several areas of the
      hospital. Running costs for the first year were 30,000 Pounds. An agreement with
      the hospital pharmacy has been pivotal to the success of the scheme.

PMID- 12073515
TI  - Data briefing. Japan's social insurance.

PMID- 12073516
TI  - [Laparoscopic cryoablation of liver tumors].
AB  - BACKGROUND: Hepatic resection remains the gold standard form of treatment for
      patients with liver metastases. However, only a small percentage of patients are
      suitable for resection. Local ablation techniques such as cryotherapy have been
      used with some success in patients with hepatic tumors. We reviewed our
      experience with cryotherapy via the laparoscopic approach. METHODS: Eighteen
      patients suffering from unresectable liver tumor were treated at our department.
      Ten patients suffered from colorectal liver metastases, eight patients suffered
      from hepatocellular carcinoma. Laparoscopic treatment was performed under general
      anesthesia commencing with laparoscopy and laparoscopic ultrasound (LAPUS) for
      accurate disease staging. Patients having extrahepatic liver spread were
      excluded. Patients with unresectable liver tumor with no evidence of extrahepatic
      disease were then treated with laparoscopic cryoablation. The laparoscopic
      cryoablation system consisted of two integrated parts: The cryoablation system
      (Cryo-hit, Galil Medical, Israel; employing Argon/Helium gases using 5 mm
      needles) combined with Laparoscopic ultrasound system using a 10 mm US probe
      (Sharplan U-sight system, Israel). Cryoablation treatment (two cycles of 10
      minutes each) starts with the insertion of the cryo-needle under US guidance. Two
      or more needles are inserted according to tumor configuration. Treatment is
      continuously monitored by LAPUS. RESULTS: Morbidity consisted mostly of fever
      (4/18, 22%) due to atelectasis. Two patients bled and were treated
      conservatively. One patient died following the development of myocardial
      infarction 3 days after treatment. FOLLOW-UP: After 13-40 months, mean period of
      16 months. Eight patients are alive (17, 18, and 29 months, hepatocellular
      carcinoma; 13-32 months, metastatic disease). It is important to note that 2
      patients have had repeat LC and one patient had 3 LC treatments for recurrent
      metastatic disease. CONCLUSIONS: LC of irresectable liver tumors is feasible,
      well tolerated and carries relatively low morbidity with no procedure-related
      mortality. Repeat treatment is possible. Long term survival may be achieved.

PMID- 12073518
TI  - [Minimally invasive surgery for gastric cancer].
AB  - The use of laparoscopic surgery in the treatment of gastric cancer has not yet
      met with widespread acceptance. Hence, it should be regarded as still in the
      developmental phase. We present our experience with laparoscopic gastrectomy in
      four patients with gastric cancer during the last few months. The postoperative
      course was uneventful in all patients. It seems that although it remains a
      challenging procedure, laparoscopic gastrectomy should be considered as a
      possibility when planning this procedure.

PMID- 12073517
TI  - [Hyperthermia combined with radiation therapy in the treatment of cancer
      patients].
AB  - Hyperthermia [HT] combined with radiation therapy [XRT] has been confirmed in
      several randomized studies to be more effective then XRT alone in various
      cancers. In this study we presented our experience using this combined modality.
      One hundred and fifty one HT sessions in 40 fields were delivered to 24 patients
      with breast cancer, melanoma and other tumors. Twelve patients [83 HT in 19 HT
      fields] were followed-up in a single institution. Complete and partial responses
      were seen in 9/19 [47%] and 8/19 [42%] HT fields during 2-12 months. Additional 2
      HT fields were treated on an adjuvant basis [one due to positive deep surgical
      margins and the other due to a second local recurrence in chest wall]. We
      conclude that HT-XRT is an effective treatment and should widely be used in
      appropriately selected cancer patients.

PMID- 12073519
TI  - [Local thrombolysis for the treatment of patients with proximal deep vein
      thrombosis of the leg].
AB  - BACKGROUND: Standard anticoagulatn therapy for lower extremity DVT does not
      distinguish between proximal and distal veins. Catheter directed thrombolytic
      therapy is a new emerging aggressive option for suitable patients with proximal
      DVT. OBJECTIVES: Review of the literature and presentation of two patients in
      whom the procedure was successfully performed. PATIENTS AND METHODS: Two patients
      with lower extremity DVT involving the iliac and femoral veins were treated with
      catheter directed urokinase infusion in addition to conventional anticoagulant
      therapy. In both cases underlying venous stenoses were identified and treated by
      balloon angioplasty and insertion of metallic stents. Thrombolytic therapy was
      continued for 36-60 hours at a rate of 100,000 units per hour. RESULTS:
      Significant clinical and radiological improvement was obtained in both patients
      with restoration of centripetal venous flow in the deep venous system. No
      significant complication occurred. A persistent clinical benefit was seen at
      follow-up of 8 and 24 months respectively. CONCLUSIONS: Catheter directed
      thrombolytic therapy should be considered as adjuvant therapy for patients with
      acute proximal lower extremity DVT, in whom there are no contraindications.
      Underlying venous stenoses should be dilated and stented if necessary. Early
      restoration of venous flow results in rapid clinical improvement and may prevent
      the future development of post thrombotic syndrome.

PMID- 12073520
TI  - [Malignant teratocarcinosarcoma of the nose and paranasal sinuses].
AB  - Malignant teratocarcinosarcoma of the nasal cavity and the paranasal sinuses is a
      rare and invasive tumor. It is characterized by a mixture of mesenchymal and
      epithelial components, with cellular elements of a fetal nature. We describe in
      detail the first and only case in Israel of a patient with such a tumor. Only 40
      50 such cases have been described in the medical literature. We have also
      reviewed the existing literature dealing with malignant teratocarcinosarcoma.

PMID- 12073521
TI  - [Fever and chills following intravenous administration of NeyTumorin--an
      unconventional xenogenous derived peptides extract].
AB  - We report a 54 year old patient who was recently diagnosed with retroperitoneal
      recurrence of colon carcinoma, and who was admitted because of fever and chills.
      Extensive work-up yielded no source of infection, multiple blood cultures were
      sterile, and symptoms resolved within two days. During hospitalization, it was
      learned that her symptoms appeared an hour after a drug named NeyTumorin was
      administered to her intravenously by an alternative medicine practitioner.
      NeyTumorin is part of cell therapy, which is an alternative medicine therapy
      involving the administration of farm animals derived preparation of peptides from
      several organs, including the diencephalon and hypophysis. This case underscores
      the risk of invasive alternative medicine treatments, which are not subject to
      adequate scrutiny by the health authorities.

PMID- 12073522
TI  - [Pediatric flexible endoscopy of the upper airway in the outpatient clinic].
AB  - Flexible nasopharyngoscopy has become an important examination of the upper
      airway in children. It is performed in the outpatient clinic in children of all
      ages under local anesthesia. We reviewed 190 consecutive examinations of children
      aged 3 days to 17 years, that were referred to the pediatric ENT clinic between
      1999 and 2000. The following parameters were analyzed: demographic details,
      indications, physical findings, patient cooperation, reliability, and
      recommendations for further evaluation or treatment. The most common indication
      for endoscopy was nasal obstruction in 56 patients (30.1%). In this group 25 had
      an obstructing adenoid and were referred for adenoidectomy. Hoarseness was the
      second most common complaint in 40 patients (21.5%). Thirty-one of those patients
      had vocal cord nodules. The most common finding was adenoid hypertrophy in 56
      patients (30.1%). No pathology was found in 34 examinations (18.3%). Although a
      significant correlation between patient cooperation and examination reliability
      was seen, in most cases good reliability was obtained even in the presence of
      poor cooperation. The procedure was easy to perform and had no complications.
      This study emphasizes the advantages of awake flexible nasopharyngolaryngoscopy
      in the diagnosis of upper airway pathologies in children.

PMID- 12073524
TI  - [Fading into extinction?].

PMID- 12073523
TI  - [Home intravenous antibiotic therapy for osteomyelitis patients].
AB  - OBJECTIVES: To evaluate both the safety and the costeffectiveness of the Home
      Intravenous Antibiotic Therapy (HIAT) program for the treatment of patients with
      osteomyelitis in the district of Haifa and Western Galilee. METHODS: We checked
      the medical records of all the patients with osteomyelitis who had been treated
      at home with intravenous antibiotics during 1999-2000. We reviewed their records
      for etiological agents, types of antibiotics given, complications and cost
      evaluation. RESULTS: During the two year period (January 1999 to December 2000),
      52 patients received 55 courses of HIAT. The total duration of treatments was
      1187 days. Eighty-five percent of the patients were referred from clinical
      departments from one of the medical centers in our area. In 54.6% of cases the
      infecting agent is unknown. Among the known ones, Staphylococci and Pseudomonas
      aeruginosa were the most prevalent pathogens. Penicillins and Cephalosporins were
      the most common antimicrobial agent prescribed. The HIAT program saved NIS.
      1,299,765 (approx. $365,000) during 1999-2000. Only minor complications were
      present. CONCLUSIONS: HIAT for the treatment of patients with osteomyelitis is
      effective, safe and comfortable for the patients and has an important economic
      impact.

PMID- 12073525
TI  - [The physician scientist, problems and hope].
AB  - The dawn of the third millenium views a shift of focus from society to the
      individual. Personal accomplishments, comfort and well being have priority over
      such issues as contribution to society and general good. Physicians, among other
      professionals, have shifted their priorities to personal and economic status
      rather than an academic position. Despite this trend, the number of researchers
      among hospital physicians has not declined and the quality of research by
      clinicians seems to improve. There is, however, some retardation in our progress,
      relative to other industrial countries mainly due to major shrinkage of public
      financial resources. Physicians-scientists are those who generate the ideas for
      research in medicine and those who best apply new data to clinical practice.
      Indeed they constitute the backbone of the medical system. In order to ensure
      future preservation of the quality of medical care, clinical and basic research
      in medical schools and in hospitals must receive better support.

PMID- 12073526
TI  - [Prevention of errors in medicine--is it feasible?].

PMID- 12073527
TI  - [Agrin acts at the nerve-muscle synapse in the glomerular basal membrane and on T
      lymphocytes].
AB  - The role of agrin, a large proteoglycan containing heparan-sulfate in the
      synaptic cleft, has been elucidated in recent years. The molecule released from
      the motor-neuron endplate, binds to a complex of 2 adjacent receptors at the post
      synaptic myotube surface. It binds first to MASC (myotube associated specific
      component) and thus triggers a signal at the MuSK (muscle-specific kinase)
      receptor that generates tyrosine phosphorylation. A cascade of further responses
      of RATL and rapsyn leads to the aggregation of acetylcholine receptors. Lately,
      agrin is also implicated as a sulfated proteoglycan in the glomerular basement
      membrane as a barrier preventing albuminuria. It is also hypothesized that agrin
      functions at the surface of activated T-lymphocytes as a part of the recognition
      process between antigen-presenting-lymphocytes and responding T cells.

PMID- 12073528
TI  - [Avoiding human errors in the hospital--mission possible?!].
AB  - The way to combat the high frequency of errors and mistakes that endanger both
      the physician and the patient is by root cause analysis of accidents as well as
      investigation of "near misses". There is a need for a new approach to error
      prevention by re-education of the medical teams. A few examples are presented on
      how to approach an untoward event so as to learn from it rather than punish.

PMID- 12073529
TI  - [Research approaches in the behavioral genetics of psychiatric disorders].
AB  - Multi-factorial inheritance combines genetic and environmental effects. Each
      factor contributes a relatively small part to the overall phenotype. Multi
      factorial multi-genetic illnesses are usually divided into two categories: 1.
      Continuous variation of the normal distribution--phenotypes that can be measured
      within the normal scale (i.e. blood pressure). A normal distribution is obtained
      and the mean is in the middle. 2. Multi-factorial threshold trait--a threshold
      separates between the existence or absence of the phenotype. The curve of
      distribution obtained only predicts sensitivity for the illness rather than it's
      existence, since the illness appears only beyond a specific threshold, which
      represents a specific combination of defected genes. Mental illnesses (psychoses,
      affective disorders and neuroses) are multi-factorial illnesses, affected at a
      level of approximately 50% by inheritance. These diseases are not inherited in a
      simple Mendelian way, and, most probably, many genes are involved. Today, there
      is still no biochemical or molecular marker for any of the mental illnesses, and
      diagnosis of patients is obtained according to behavioral accepted scales. The
      aim of behavioral genetics is to understand the interaction between genes and
      behavioral variability among individuals. Most behaviors are complex, and when a
      genetic influence is observed, we can not point at a single responsible gene.
      Behavioral genetics targets to identify multiple genes and to understand the
      contribution of each of them to a specific behavioral trait. Methods to study
      multi-gene diseases include linkage analysis, family studies, twin and adoption
      studies, search for candidate genes affected by drug therapy of the patients,
      analysis of candidate genes using knockout mice and SNP's, methods that identify
      the effect of specific genes on behavior by QTL, and gene expression using DNA
      differential display and DNA microarray chips. The present review summarizes and
      exemplifies these issues.

PMID- 12073530
TI  - [Behcet's disease--clinical presentation, diagnostic and therapeutic approach].
AB  - Behcet's disease is a complex, multisystem disease first described in 1937 by the
      Turkish dermatologist, Hulusi Behcet. In his original description, Behcet
      referred to a symptom complex of recurrent oral aphthous ulcers, genital aphthae,
      and iritis that could lead to blindness. Today we know that Behcet's disease is
      much more than a "triad syndrome" and it may also involve the gastrointestinal,
      central nervous system and large vessels. As yet, there are no existing
      diagnostic laboratory tests or curative treatments for Behcet's disease. Howver,
      genetic studies have identified those who are at risk and newer molecular
      biologic investigations further elucidate the pathogenesis of the disease. The
      treatment of Behcet's disease depends on clinical manifestations and the severity
      of the disease. Although various therapeutic modalities have been employed for
      Behcet's disease, treatment is still unsatisfactory. Treatment modalities include
      local, systemic, or surgical approaches. Only limited success has been achieved
      with classic agents such as: colchicine, indomethacin, chlorambucil, and systemic
      corticosteroids. New therapeutic approaches have been introduced for Behcet's
      disease using cyclosporine, thalidomide, interferon, high-dose corticosteroids or
      cyclophosphamide therapy. In this article we summarized the clinical and
      diagnostic approach for Behcet's disease and the current therapy indicated for
      different clinical presentations of the disease.

PMID- 12073531
TI  - [Air pollution, particulate matter and human health].
AB  - Air pollution in Israel is an increasing problem, mainly due to the sharp rise in
      the number of motor vehicles, and in particular diesel engined vehicles. It has
      become a focus of interest for the general public, as part of the rising
      awareness of Israelis to environmental matters, and for the medical community in
      particular, due to the associated rise in the incidence of asthma. The present
      review deals with the importance of the role of fine particulate matters (PM10
      and PM2.5), while more classical pollution parameters, such as Sulfate and
      Nitrate Oxides, currently seem to be less relevant in predicting associated
      health effects. There is a need for an intensification of applied research in
      this field in Israel, in orders to establish a better data platform required for
      defining the national health policy in this field.

PMID- 12073532
TI  - [Legal aspects of the psychiatric treatment of minors].
AB  - This article deals with the involvement of the law in the psychiatric treatment
      of minors through the directives it gives with regards to examination, diagnosis,
      treatment and hospitalization of minors. In recent years changes have been made
      in the law dealing with these issues. These were set out in the 1995 amendments
      to two laws: "The Law of the Treatment and Supervision of Minors" and "the Law of
      the Treatment of the Mentally Ill". The amendments include changes in the
      procedural processes as well as the introduction of concepts which did not exist
      in the previous laws. Since these amendments have begun to be put into practice,
      the therapeutic system has discovered that problems have arisen in two areas--the
      conceptual and the practical--of the instructions of the new laws. These problems
      arise out of the difficulty in understanding what the laws actually say,
      difficulties in executing the laws, and a special clumsiness which causes it to
      miss its objective through the insistence on systems of control the likes of
      which are not found in any other branch of medicine. This article will discuss
      the above-mentioned amendments to the law with two aims in mind: to present an
      overview and clarification of a complex and complicated law with which a large
      part of the public is not competently apprised; and to present the limitations of
      this law and our comments about it.

PMID- 12073533
TI  - [Psoriasis, biblical afflictions and patients' dignity].
AB  - The currently accepted Hebrew word for psoriasis is 'sapachat'. The word
      'sapachat' is biblical and its original meaning is unknown. Similar uncertainty
      applies also to the biblical word 'tzaraat', the currently accepted Hebrew term
      for leprosy. This article discusses possible explanations of the biblical terms
      'sapachat' and 'tzaraat'. The link between 'sapachat' and psoriasis was made only
      several decades ago. The word 'sapachat' conveys a definite negative connotation,
      and imposes an emotional burden on psoriatic patients. We therefore recommend
      preferable use of the word 'psoriasis' and avoid using the offending term
      'sapachat'.

PMID- 12073534
TI  - [Parenthood--medical aspects of international adoption].
AB  - The unavailability of significant numbers of native-born children for adoption by
      local families has led to an upsurge in international adoptions throughout the
      Western world, including Israel. The sudden appearance here of large numbers of
      babies and young children from countries with a variety of indigenous infectious
      diseases has focused concern on the issue. It has also induced the Ministry of
      Health to issue guidelines to protect the well-being of the public at large, as
      well as to aid adoptive families in maintaining their own, as well as their newly
      adopted children's health. The great majority of community based primary
      caregivers are unfamiliar with the health issues surrounding internationally
      adopted children. These children merit special care and consideration. One
      possible solution, in addition to educational campaigns, and already implemented
      abroad, is the specialized training of physicians caring for large numbers of
      such children. [International Adoption, HIV, Hepatitis B, Hepatitis C,
      Tuberculosis, Syphilis].

PMID- 12073535
TI  - Progress towards poliomyelitis eradication.

PMID- 12073536
TI  - Adoption of Global Agenda on Influenza--Part II.

PMID- 12073537
TI  - [Changes in cell kinetics and clinical course in inflammatory bowel diseases].
AB  - INTRODUCTION: The pathogenesis of inflammatory bowel diseases is still unknown,
      but is accessible from several ways. One possibility is the immunohistochemical
      analysis of cellular changes in the intestinal mucosa. The increased epithelial
      cell turnover is connected with false immunological pathways in the subepithelial
      layer. Behind these disturbances which can lead to chronic remitting inflammatory
      processes the imbalance of apoptosis and proliferation plays a key role. AIM: Of
      this study is to summarize our current knowledge of the cell kinetical
      alterations considering histological activity of disease. CONCLUSIONS: On the
      basis of current understanding it is known that the apoptosis and proliferation
      of epithelial cells increase in active inflammation compare to normal, although
      an uniform standpoint of evaluating is still missing. Some alterations of
      apoptosis and antigen presentation are described in the mononuclear cells of the
      subepithelial layer. Getting acquainted with and describing the changes of cell
      kinetics provide facilities to develop new and effective diagnostical methods and
      therapies.

PMID- 12073538
TI  - [Genetic investigations in forensic medicine].
AB  - Scientific research of the last decade including the introduction of new
      molecular biological methods and mapping of the human genome allowed the
      development of a revolutionary new molecular biological approach in forensic
      medicine. The traditional serological methods study proteins, the new DNA
      analysis goes further down to study DNA structures to analyze unique individual
      features. The two main areas of DNA application in forensic medicine are
      inheritance studies and personal identification in criminal cases using
      biological traces. Using this new, reliable and reproducible method we can answer
      questions they were almost impossible in the past. This article reviews how
      molecular techniques used to detect genetic polymorphism in forensic medicine.

PMID- 12073540
TI  - [Borrelia burgdorferi Group: in-vitro antibiotic sensitivity].
AB  - Failures in the antibiotic therapy of Lyme disease have repeatedly been
      demonstrated by post-treatment isolations of the infecting borreliae. Analyses of
      the antibiotic susceptibility patterns of borreliae may help to understand the
      causes of such treatment failures and to develop new therapeutic regimens. AIMS
      AND METHODS: The three subspecies of Borrelia burgdorferi known to be pathogenic
      for humans and to differ in their virulence and organ affinity possibly may also
      show divergent susceptibilities to some common antibacterial agents. In order to
      get real clues for such probable differences we compared the efficacy of six
      antimicrobial agents against 24 borrelial tick and skin isolates belonging to the
      three subspecies of B. burgdorferi sensu lato. RESULTS: In five comparative
      evaluations, some significantly different antibiotic sensitivity of the three
      borrelial species was found. The Borrelia burgdorferi sensu stricto isolates
      showed lower sensitivity to cephalosporin, tetracycline and ciprofloxacin as well
      as a higher sensitivity to erythromycin compared to the B. afzelii and B. garinii
      isolates. The B. garinii isolates proved to be more sensitive to penicillin in
      comparison to the B. burgdorferi s.s. and B. afzelii isolates. CONCLUSIONS: In
      the light of these data, treatment failures may be interpreted by serum and
      tissue levels of the antibiotic too low for an effective killing of the infecting
      Spirochetes. However, prolonged treatment regimens applying higher dosages of
      antibiotics, in order to get complete clearing of the infection, may be linked to
      aggravated side effects. PROPOSAL: Therefore, the combination of different
      antiborrelial agents with synergistic effect seems to be a meaningful alternative
      and should be included in future studies in vitro as well as in vivo.

PMID- 12073541
TI  - [Treatment of recidive malignant gliomas with temozolomide].
AB  - INTRODUCTION: The prognosis of malignant gliomas despite of the recent advances
      of diagnostical and therapeutical techniques remains poor. The majority of
      gliomas following total removal and postoperative radiotherapy recurs. In case of
      recurrencies reoperation is rarely possible and chemotherapy is the last
      treatment modality. METHODS: Forty patients with recurrent malignant gliomas had
      been treated with temozolomide (Temodal). The treatment had to be stopped in four
      cases. RESULTS: Complete remission was observed in 3, partial in 11, progressive
      disease in 4 and stable disease in 50% of the cases with CT and/or MR images. The
      mean progress free interval was 6.25 and the mean survival time 9 months.
      According to the primary histology the mean survival time for glioblastoma
      patients was 6.8 and for anaplastic astrocytoma or mixed oligoastrocytoma
      patients 12.2 months. CONCLUSIONS: Due to its low toxicity and relatively long
      survival time after recurrency temozolomide seems to be a promising drug in the
      treatment of recurrent malignant gliomas.

PMID- 12073539
TI  - [Irbesartan: a new possibility in the treatment of hypertension].
AB  - Hypertension means a basic public health problem in many countries in the world.
      The therapeutic attempts of the last years did not fulfill the hopes pinned on
      them, and most of the patients live with blood pressure above the goal value.
      This is why there is a need for new, more efficient antihypertensive drugs. On
      the 1st of July, 2001 irbesartan (Aprovel) was introduced in practice in Hungary.
      The drug belongs to the family of the angiotensin II receptor inhibitors. Several
      clinical studies were made with irbesartan in order to evaluate its efficiency,
      tolerability and safety. In other studies it was compared with other
      antihypertensive treatments and it was found that irbesartan decreases the
      systolic and diastolic blood pressure as effectively as other first line
      medicaments. The author summarizes the most important characteristics of
      irbesartan as well as the results of those clinical studies which show evidence
      that irbesartan deserves a special place among antihypertensive drugs.

PMID- 12073542
TI  - [Orbital phlegmone caused by acute exacerbation of chronic fungal pansinusitis in
      a child].
AB  - INTRODUCTION: Invasive fungal rhinosinusitis is an aggressive, destructive
      process most commonly affecting immunocompromised hosts with mortality rate of
      approximately 60-80%. AIM OF STUDY: The authors present a child's recovery of
      orbital phlegmone due to acute exacerbation of chronic fungal pansinusitis. They
      call the attention to the possibility of ever more frequent fungal sinusitis in
      our country. METHODS: Retrospective case report of an 8 years old boy presented
      with photos. RESULTS: The recovery was promoted by supposing the chance of fungal
      origin in time. No orbital abscess was found by surgery despite of typical
      clinical appearance and MRI results. After beginning of antibacterial treatment
      and functional endoscopic sinus surgery (FESS) the even worsening clinical status
      of orbital phlegmone raised the possibility of fungal origin, which was verified
      by mycological examination. The antimycotic treatment, which had been started in
      time was followed by complete recovery. Due to scarring in the medial rectus
      muscle, diplopia was the only complication which needs further ophthalmological
      controls. CONCLUSIONS: Supposition and verification of chance of fungal origin is
      essential in cases of chronic inflammation of paranasal sinus and/or their
      complications for complex recovery.

PMID- 12073544
TI  - [Status epilepticus and its treatment].
AB  - Status epilepticus is an emergency situation that can often lead to death or
      neurocognitive deficits despite adequate therapy is conducted. Etiology and
      prognosis can be widely heterogeneous. Knowledge of the basic pathophysiologic
      mechanisms has altered the definition of status epilepticus and the emphasis of
      therapy has also changed according to that. Today, with neuroprotective approach
      and recognition of the importance of time-window the management of generalised
      tonic clonic status became an emergency or critical care task, because
      intratracheal narcosis is more often and earlier the therapy of choice and even
      the sufficient treatment can convey serious side effects. In the article, the
      authors describe the systemic and cerebral pathophysiologic factors during
      seizure. The authors offer flow-charts illustrating the treatment of patients
      with generalised tonic clonic status to make the daily work of physicians easier.
      Early on critical care treatment and multidisciplinary approach is the pledge of
      reduction in mortality and morbidity.

PMID- 12073543
TI  - [Comment on Borrelia burgdorferi Group infections].

PMID- 12073545
TI  - [Outbreak of human rotavirus infection in an adult community].
AB  - INTRODUCTION: Group A rotaviruses are known as the major cause of severe
      dehydrating diarrhoea in infants. AIMS: In adults, the rotavirus infections are
      usually asymptomatic. In the present study the authors report a group A rotavirus
      outbreak in a psychiatric nursing home for adults. RESULTS: The outbreak lasted 3
      weeks; the attack rate was 20%. The mean age of patients was 39 y (range 21 to
      65; n = 25). The symptoms were mild, and most of the patients recovered within 2
      or 3 days. The epidemiological data suggested that the virus was introduced by a
      patient, and it was transmitted by person-to-person route. Rotavirus positive
      specimens were characterised by serotyping and electropherotyping. The serotype
      specific monoclonal antibody immunoassay demonstrated the circulation of a common
      strain with G1 specificity. These samples shared identical genome profile with
      strains circulated in the paediatric communities of the country. CONCLUSION: In
      Hungary, this is the first published gastroenteritis outbreak among adults caused
      by group A rotaviruses with G1 serotype specificity.

PMID- 12073546
TI  - [The role of electronic databases in practical decision making in the care of
      patients with cerebrovascular diseases].
AB  - The information revolution of recent years, the general accessibility of
      computers and especially the Internet, provided the possibility of immediate
      access to the newest and most reliable results of clinical research in everyday
      medical practice. When a question arises regarding the care of a certain patient,
      we can have answers within minutes. Summaries of systematic reviews of the
      Cochrane Library and abstracts of papers of several thousand journals indexed on
      MEDLINE are available free of charge. In addition, over 70,000 Internet home
      pages provide some sort of health care information. The fast accessibility of
      information made it possible to apply a new method, called evidence-based
      medicine, in everyday practice. This method implies the effective search of an
      answer to a well formed question, and the critical evaluation of the results
      found during the search. This paper summarises the most important electronic
      databases that can be used in the care of patients with cerebrovascular diseases.
      The paper emphasises the advantages and dangers of the use of the Internet.
      Enlisted are the most important English- and Hungarian-language home pages with
      information on cerebrovascular diseases. Internet addresses of home pages
      providing methodological help in critically evaluating the literature are also
      given. The paper summarises the most important questions to consider when we want
      to evaluate the validity and importance of papers on diagnostic methods, on
      prognosis, on treatment effect, when we read systematic reviews, economic
      evaluations, clinical decision analyses and guidelines.

PMID- 12073547
TI  - [Heat-killed Mycobacterium bovis-Bacillus Calmette-Guerin prevents experimental
      respiratory tract eosinophilia in mice].
AB  - INTRODUCTION: The increased prevalence of asthma has become a major public health
      issue worldwide. It has been proposed that this increase is due to the steady
      decline of infectious diseases such as tuberculosis. AIM OF THE STUDY: Supporting
      this view was, the suppressive effect of live Bacillus Calmette-Guerin (BCG)
      infection on allergen (ovalbumin) induced airway eosinophilia was published
      previously. METHODS: Next the authors compared the effects of live, heat killed
      BCG and purified protein derivative of Mycobacterium tuberculosis (PPD) on a
      murine model of ovalbumin induced airway eosinophilia. RESULTS: The results
      showed that both live and heat killed BCG, but not PPD strongly suppressed airway
      eosinophilia. This inhibition was correlated with the reduced number of Th2 cells
      in the lung. CONCLUSION: Their data support the hypothesis that the application
      of bacterial antigens may be a safe vaccination method against asthma in the
      future.

PMID- 12073548
TI  - [Significance of anatomy in medical and dental education at the turn of the
      century].

PMID- 12073549
TI  - Characterization of the genome of the mealybug Planococcus lilacinus, a model
      organism for studying whole-chromosome imprinting and inactivation.
AB  - The co-occurrence of three chromosome-wide phenomena--imprinting, facultative
      heterochromatization and diffuse centromere--in the mealybug Planococcus
      lilacinus makes investigation of the genomics of this species an attractive
      prospect. In order to estimate the complexity of the genome of this species, 300
      random stretches of its DNA, constituting approximately 0.1% of the genome, were
      sequenced. Coding sequences appear to constitute approximately 53.5%, repeat
      sequences approximately 44.5% and non-coding single-copy sequences approximately
      2% of the genome. The proportion of repetitive sequences in the mealybug is
      higher than that in the fruit fly Drosophila melanogaster (approximately 30%).
      The mealybug genome (approximately 220 Mb) is about 1.3 times the size of the fly
      genome (approximately 165 Mb) and its GC content (approximately 35%) less than
      that of the fly genome (approximately 40%). The relative abundance of various
      dinucleotides, as analysed by the method of Gentles and Karlin, shows that the
      dinucleotide signatures of the two species are moderately similar and that in the
      mealybug there is neither over-representation nor under-representation of any
      dinucleotide.

PMID- 12073550
TI  - Segregation of autosomes during spermatogenesis in the peach-potato aphid (Myzus
      persicae) (Sulzer) (Hemiptera: Aphididae).
AB  - Most aphids are cyclic parthenogens, so are ideal models in studies of the
      mechanisms and consequences of sex and recombination. However, owing to a
      shortage of physical and genetic markers, there have been few studies of the most
      fundamental genetic processes in these organisms. For example, it is not known
      whether autosomal segregation during male spermatogenesis is in Mendelian
      proportions: we address that question here. The aphid Myzus persicae has a
      typical karyotype of 2n = 12 in females (XX), while males are XO (2n = 11).
      During male meiosis, only the spermatocytes with an X chromosome are viable. We
      hypothesized that assortment of autosomes might be non-random because chromosomal
      imprinting leading to elimination of the paternal autosomes is seen in the
      closely related coccoids. In other aphid models, we have observed segregation
      distortions at single microsatellite loci (Wilson, 2000). Such distortions may
      have nothing to do with 'selfish' behaviour, but may be caused by mutation
      accumulation causing fitness differentials. Thus single-locus distortions might
      be predicted to be more likely to be detected via the male lines of clones that
      have lost the ability to reproduce sexually (male-producing obligate
      parthenogenesis (androcyclic)). Using microsatellites we show that genetic
      imprinting or selfish autosome behaviour does not occur in male M. persicae.
      Generally, loci segregated in Mendelian proportions in both sexes of cyclically
      parthenogenetic (holocyclic) clones. However, in androcyclic clones, segregation
      distortions consistently involved the same two autosomes. This is consistent with
      linkage of markers to deleterious mutations associated with a loss of sexual
      reproduction.

PMID- 12073551
TI  - Extending the coalescent to multilocus systems: the case of balancing selection.
AB  - Natural populations are structured spatially into local populations and
      genetically into diverse 'genetic backgrounds' defined by different combinations
      of selected alleles. If selection maintains genetic backgrounds at constant
      frequency then neutral diversity is enhanced. By contrast, if background
      frequencies fluctuate then diversity is reduced. Provided that the population
      size of each background is large enough, these effects can be described by the
      structured coalescent process. Almost all the extant results based on the
      coalescent deal with a single selected locus. Yet we know that very large numbers
      of genes are under selection and that any substantial effects are likely to be
      due to the cumulative effects of many loci. Here, we set up a general framework
      for the extension of the coalescent to multilocus scenarios and we use it to
      study the simplest model, where strong balancing selection acting on a set of n
      loci maintains 2n backgrounds at constant frequencies and at linkage equilibrium.
      Analytical results show that the expected linked neutral diversity increases
      exponentially with the number of selected loci and can become extremely large.
      However, simulation results reveal that the structured coalescent approach breaks
      down when the number of backgrounds approaches the population size, because of
      stochastic fluctuations in background frequencies. A new method is needed to
      extend the structured coalescent to cases with large numbers of backgrounds.

PMID- 12073552
TI  - Clinal variation in Drosophila serrata for stress resistance and body size.
AB  - Clines for size and stress resistance traits have been described for several
      Drosophila species and replicable clines across different species may indicate
      climatic selection. Here we consider clines in stress resistance traits in an
      Australian endemic species, D. serrata, by comparing levels of variation within
      and among isofemale lines initiated with flies collected from the eastern coast
      of Australia. We also consider clinical variation in chill coma recovery, a trait
      that has recently been shown to exhibit high levels of variation among Drosophila
      species. Patterns were compared with those in the cosmopolitan species D.
      melanogaster from the same area. Both desiccation and starvation resistance
      showed no clinical pattern despite heritable variation among isofemale lines. In
      contrast chill coma resistance exhibited a linear cline in the anticipated
      direction, resistance increasing with latitude. Body size was measured as wing
      length and body weight. Both traits showed geographic variation and strong non
      linear clines with a sharp reduction in size in the tropics. These results are
      discussed in the context of climatic selection and evolutionary processes
      limiting species borders.

PMID- 12073553
TI  - Mapping of genetic loci that change pheromone discrimination in Drosophila males.
AB  - Reproduction in individual animals of sexual species depends largely upon their
      ability to detect and distinguish specific signal(s) among those produced by
      various potential sexual partners. In Drosophila melanogaster males, there is a
      natural polymorphism for discrimination of female and male principal pheromones
      that segregates with chromosome 3. We have mapped two loci on chromosome 3 that
      change sex-pheromone discrimination in males. We successively exploited meiotic
      recombination, deficiencies and enhancer-trap strains; excision of the transposon
      in two selected enhancer-trap strains clearly reverted the discrimination
      phenotype. These results indicate that pheromonal discrimination is a character
      that can be genetically manipulated, and provide further insights into the
      evolution of the specific mate recognition system.

PMID- 12073554
TI  - The effects of selected sampling on the transmission disequilibrium test of a
      quantitative trait locus.
AB  - We investigate how sampling of parents or children based on their extreme
      phenotypic values selected from clinical databases would affect the power of
      identification of quantitative trait loci (QTL) by a transmission disequilibrium
      test (TDT). We consider three selective sampling schemes based on the selection
      of phenotypic values of parents or children in nuclear families: (1) two
      children, one of extreme value, the other random; (2) two children extremely
      discordant; (3) one parent of extreme value. Other family members not specified
      will be recruited randomly with regard to phenotypic values. Our study shows that
      the second sampling scheme can always enhance the power for QTL identification,
      sometimes dramatically so. The increase in the statistical power of the TDT is
      particularly dramatic when h2 at the QTL under test is small or intermediate
      (e.g. 0.05 or 0.10). For the other two sampling schemes, under dominant effects
      at the QTL, the power is always increased relative to random sampling; however,
      under recessive or additive genetic effects, the power gain is generally minor or
      even decreased a little sometimes. Allele frequencies at the QTL and the
      selection stringency are important for determining the effect of selective
      sampling on the power of QTL identification. Our study is useful as a practical
      guideline on how to perform the TDT efficiently in practice by taking advantage
      of the extensive databases accumulated that are enriched with people of extreme
      phenotypic values.

PMID- 12073555
TI  - Use of randomization testing to detect multiple epistatic QTLs.
AB  - Here, we describe a randomization testing strategy for mapping interacting
      quantitative trait loci (QTLs). In a forward selection strategy, non-interacting
      QTLs and simultaneously mapped interacting QTL pairs are added to a total genetic
      model. Simultaneous mapping of epistatic QTLs increases the power of the mapping
      strategy by allowing detection of interacting QTL pairs where none of the QTL can
      be detected by their marginal additive and dominance effects. Randomization
      testing is used to derive empirical significance thresholds for every model
      selection step in the procedure. A simulation study was used to evaluate the
      statistical properties of the proposed randomization tests and for which types of
      epistasis simultaneous mapping of epistatic QTLs adds power. Least squares
      regression was used for QTL parameter estimation but any other QTL mapping method
      can be used. A genetic algorithm was used to search for interacting QTL pairs,
      which makes the proposed strategy feasible for single processor computers. We
      believe that this method will facilitate the evaluation of the importance at
      epistatic interaction among QTLs controlling multifactorial traits and disorders.

PMID- 12073557
TI  - Role of pH response in Candida albicans virulence.
AB  - Over 25 years ago it was noted that the pH of the culture medium influenced germ
      tube formation of Candida albicans, an opportunistic fungal pathogen. This simple
      observation has been the stimulus for a number of investigations to discern the
      mechanisms controlling this response and the significance of this response to the
      biology of C. albicans. Recent studies have demonstrated that a signaling pathway
      conserved in several fungal species regulates this morphological response to
      ambient pH and controls the pH-conditional expression of multiple genes.
      Significantly, C. albicans responds to the pH of the host niche and this response
      is critical for virulence.

PMID- 12073556
TI  - Mapping quantitative trait loci with epistatic effects.
AB  - Epistatic variance can be an important source of variation for complex traits.
      However, detecting epistatic effects is difficult primarily due to insufficient
      sample sizes and lack of robust statistical methods. In this paper, we develop a
      Bayesian method to map multiple quantitative trait loci (QTLs) with epistatic
      effects. The method can map QTLs in complicated mating designs derived from the
      cross of two inbred lines. In addition to mapping QTLs for quantitative traits,
      the proposed method can even map genes underlying binary traits such as disease
      susceptibility using the threshold model. The parameters of interest are various
      QTL effects, including additive, dominance and epistatic effects of QTLs, the
      locations of identified QTLs and even the number of QTLs. When the number of QTLs
      is treated as an unknown parameter, the dimension of the model becomes a
      variable. This requires the reversible jump Markov chain Monte Carlo algorithm.
      The utility of the proposed method is demonstrated through analysis of simulation
      data.

PMID- 12073558
TI  - [In vitro growth of human pathogenic fungi on different stocking fabrics].
AB  - Athlete's foot and onychomycosis can be aggravated due to inappropriate footwear.
      In this study we examined whether stockings of synthetic and mixed fabrics may
      influence the growth behaviour of the commonly isolated fungi Trichophyton
      rubrum, Trichophyton mentagrophytes and Candida albicans. A standardized
      suspension of each fungus was given to each sample of twelve stockings of
      different materials. The size of the growing colonies and the velocity of their
      growth were measured and compared to each other. Based on our data stockings
      depending on their fabric mixture seem to support or inhibit respectively the
      growth of fungi. Stockings composed of polyamide and a high percentage of
      polyurethane (Elasthan) and silk stockings as well may likely promote the fungal
      growth.

PMID- 12073559
TI  - [Risk factor for invasive zygomycosis in patients with hematologic malignancies].
AB  - Zygomycosis (mucormycosis) is a relatively uncommon infection in
      immunocompromised patients most often diagnosed in patients with haematological
      malignancies and neutropenia. Postmortem series demonstrate a high mortality rate
      up to 80%. Pulmonary involvement mimicking the more frequently diagnosed invasive
      aspergillosis is the typical clinical presentation. Other risk factors for the
      development of zygomycosis that have been described in other patient populations
      include diabetic ketoacidosis, iron overload, use of deferoxamine and steroids.
      If these factors are also associated with zygomycosis in patients with
      haematological malignancies has not been described. In a retrospective case
      control study including 13 patients with zygomycosis and 13 control patients with
      the same underlying diseases, without zygomycosis we determined the frequency of
      various risk factors. Patients with zygomycosis experienced a longer period of
      neutropenia (17 vs. 13 days) and lymphopenia (23 vs. 20 days). A relapse of their
      underlying disease was diagnosed more frequently in patients with zygomycosis
      (7/13 vs. 3/13) as were a diagnosis of diabetes mellitus (6/13 vs. 3/13) and a
      cardiovascular disease (6/13 vs. 1/13). The previous use of steroids was more
      frequent in patients with zygomycosis (8/13 vs. 4/13) as was a systemic
      antifungal prophylaxis with itraconazole (9/13 vs. 4/13). Knowledge of these risk
      factors may be of benefit in diagnosing and monitoring zygomycosis in patients
      with haematological malignancies.

PMID- 12073560
TI  - [Molecular biological identification of Cuninghamella spec].
AB  - Among the genus Cunninghamella, so far C. bertholletiae is known to be the only
      clinically relevant species. Correct identification of C. bertholletiae is not
      possible with classical methods. PCR and sequencing of the internal transcribed
      spacer (ITS) region was used to identify seven of nine clinical isolates as C.
      bertholletiae and two as C. echinulata. Also an isolate of the surrounding area
      of one patient infected with C. echinulata could be identified as C. echinulata.
      High homology in the ITS region was found within the isolates of C.
      bertholletiae. Within the species C. echinulata and C. elegans a differentiation
      on subspecies level was achieved by an analysis of restriction fragment length
      polymorphism of the ITS amplicons after incubation with TaqI and HinfI. Similar
      results were obtained by PCR fingerprinting of the complete DNA with the single
      microsatellite DNA primers (GTG)5 and (GAC)5. For the first time C. echinulata
      could be identified as agent of zygomycosis in humans.

PMID- 12073561
TI  - [Dehydroepiandrosterone metabolism by Epidermophyton floccosum].
AB  - Steroid hormones may be relevant for the fungus-host relation in dermatophytoses.
      In contrast to most other hosts of dermatophytes, humans are characterized by a
      high cutaneous concentration of the adrenal androgen dehydroepiandrosterone
      (DHEA) and its sulphate (DHEAS). To investigate whether the strictly
      anthropophilic dermatophyte Epidermophyton floccosum can metabolize this steroid
      hormone, cultures of E. floccosum were supplemented with DHEA. After 5 days of
      incubation the steroids in the culture supernatants were extracted and
      differentiated by gaschromatography and massspectrometry (GC-MS). The results
      show that a nearly complete metabolization of DHEA by E. floccosum leads to the
      formation of multiple new steroids/metabolites some of which have not been
      reported before. Therefore, this fungus could possibly mediate the hormone
      regulated cutaneous defense mechanisms of the host by an intraepidermal
      metabolization of DHEA.

PMID- 12073562
TI  - Influence of voriconazole and fluconazole on Candida albicans in long-time
      continuous flow culture.
AB  - We investigated the influence of voriconazole and fluconazole in a long term
      trial of continuous flow culture (cfc) up to 9 days. The effects of these azoles
      were different in dependence on the growth circumstances. Under anaerobic
      conditions a fungicidal effect of voriconazole was detectable, defined by an
      inhibition of 99.9%. This also applied to fluconazole for the majority of tested
      strains of C. albicans. Under aerobic conditions with an otherwise similar
      situation we found only a fungistatic reaction (inhibition of 90%). Fluorescence
      microscopy comparing fungal morphology in biofilms on glass surfaces in the cfc
      revealed a differentiation into blastospores, germ tubes, pseudomycelia and
      mycelia in the control trial after a cultivation of 8 days. Under anaerobic
      conditions with azoles only some single cells could be found, sometimes in cell
      detritus. The adhesion was clearly reduced. Under aerobic conditions more
      blastospores but no differentiated mycelia were to be seen.

PMID- 12073563
TI  - [Histologic studies on otomycosis].
AB  - Fungal infections of the ear are mostly described as mycoses of the auditory
      canal. The aim of our investigations was to find out how fungi colonize the ear
      in immunocompetent patients. In the years from 1993 to 2000, 128 patients
      suspected of having otomycosis were examined. Of these 115 patients suffered from
      chronic otitis media with persisting tympanum perforation and otorrhea. A further
      13 patients had clinical signs of otitis externa only. In 54 out of 139 samples,
      fungi were found in the auditory canal, in five on the tympanic membrane, and in
      five in the middle ear. Two-thirds were isolated as moulds and one-third as
      yeasts. Dominating species were Aspergillus niger and Candida parapsilosis.
      Samples of 15 patients suspected of having mastoiditis or cholesteatoma were
      examined histologically. Fungal hyphae were observed in the middle ear cavity
      and/or between horny lamellae of cholesteatoma in 4 patients. In the middle ear
      of immunocompetent patients chronic-hyperplastic (polypous) inflammation was
      detected with increased production of mucus, which probably promotes the
      colonization with pathogenic fungi as in the middle ear just like in the auditory
      canal.

PMID- 12073564
TI  - [Blood coagulation in domestic deep-seated mycoses].
AB  - Activation of blood coagulation to a varying extent affect the course of domestic
      invasive mycoses. Upon invasion of blood vessels by Candida or aspergilli,
      occasionally thrombi are formed, which may cause septic embolism. In the course
      of mucormycosis (syn. zygomycosis) thrombotic occlusion of afflicted blood
      vessels and subsequent necrosis of dependent tissue regularly occurs. Coagulation
      during candidosis or aspergillosis may be triggered by secreted aspartic
      proteinases which are able to activate factor X as has been shown previously [1,
      2]. During mucormycosis, severe blood coagulation apparently is due to
      paracoagulation of fibrinogen which is triggered by low concentrations of
      extracellular fungal subtilisin-like proteinase (Arp). The enzyme is also able to
      inactivate the major inhibitor of blood coagulation (antithrombin III). Recent
      findings on the action of Arp are discussed.

PMID- 12073565
TI  - [A historical view of dermatomycology].
AB  - This historical review is focussed on clinical aspects of dermatomycology on one
      hand and on the discovery of fungi as pathogenic agents in dermatologic diseases
      on the other hand. This latter period in the 19th century established the
      beginning of dermatomycology. The basic role of fungus-host-interrelationship is
      mentioned with reference to earliest microscopical investigations of this issue
      on plants by Marcello Malphighi in the late 17th century.

PMID- 12073567
TI  - [Medical mycology in Germany--the present status for the 40th anniversary of the
      German Mycology Society].

PMID- 12073566
TI  - [Mode of action of ciclopiroxolamine on Candida albicans].
AB  - Candida albicans is a common pathogen causing both superficial and invasive
      mycoses. The hydroxypyridone ciclopiroxolamine belongs to antimycotic drugs used
      for treatment of superficial mycoses. Whereas the mode of action of other
      antimycotics, for example the azoles, is well known, the specific action of
      ciclopiroxolamine is poorly understood. There are hints, that ciclopiroxolamine
      acts as a potential chelating agent and influences some cellular processes by
      chelating metal ions. Consequently, the antimycotic effectiveness of
      ciclopiroxolamine could be due to a general reduced viability of the fungus, or
      due to a higher sensitivity of a fungus against the human immune system as well
      as due to a reduced capability to produce some specific virulence factors that
      are indispensable for infection. Nevertheless, iron metabolism seems to play a
      major role in its effect.

PMID- 12073568
TI  - [Current topics on classification and nomenclature of bacteria. 11. From
      phylogenetic tree to phylogenetic map].

PMID- 12073569
TI  - [A multicenter study of a new Helicobacter pylori selective medium. Columbia
      horse blood agar HP].
AB  - We conducted a study for the growth of and selectivity for the desired
      microorganisms using a newly developed selective culture medium for Helicobacter
      pylori, Columbia horse blood agar HP (CHBHP), at three different Japanese
      clinical laboratories, Hokkaido, Kanto and Kyusyu. When standard strains and
      clinical isolates of H. pylori were examined, the recovery of the organism on the
      CHBHP media was comparable to that of conventional selective and nonselective
      media. However, colonies were obviously larger on the CHBHP media. These media
      yielded the highest H. pylori positive rate for clinical specimens at all the
      three laboratories. The detection rate of the CHBHP media in H. pylori-positive
      specimens was higher than that of media commonly used at the three laboratories
      (98.1% to 100% vs. 88.0% to 96.2%). The CHBHP media also achieved a higher
      detection rate for specimens from H. pylori-infected animals. CHBHP media have an
      excellent growth supporting ability and selectivity originating from Columbia
      agar base and do not require the combined use of non-selective media for the
      growth and isolation of the organism, resulting in lower cost. Thus, they are
      useful media for the selective culture and isolation of H. pylori from clinical
      and animal specimens.

PMID- 12073570
TI  - [Long PCR amplification of varicella-zoster virus DNA in clinical specimens from
      the patients with varicella and herpes zoster].
AB  - Long PCR amplification of the 7.7 to 33.5 Kbp regions of varicella-zoster virus
      (VZV) genomic DNA was performed using template DNAs extracted from clinical
      specimens such as vesicle fluid and crusts which had been obtained from varicella
      or herpes zoster patients. PCR products of 7.7-14.4 Kbp in length were
      efficiently amplified from all of the 14 template DNAs of crust specimens.
      Targets of 18.6-20.0 Kbp DNA could be also amplified from 14 crust samples except
      one. From all of the 7 samples derived from infected cells, the DNA targets up to
      27.2 Kbp in length could be amplified. Whereas, the efficiency of amplification
      of 27.2 Kbp DNAs from crust samples was somewhat lower (9/14,64%) than that of
      DNAs from infected cells. In 83% (5/6) of target DNAs from infected cells,
      amplification of DNA as long as 33.5 Kbp was possible, while only in 40% (2/5) of
      these from crust specimens. From crust samples, the efficiency of amplification
      of DNA longer than 20 Kbp tended to decline. We also confirmed that long target
      DNA was amplifiable directly from vesicle fluid specimens as effective as from
      crust specimens. Restriction fragment length polymorphism (RFLP) analyses
      combined with R2-nested PCR of the long PCR products allowed classification of
      the 14 clinical specimens into 9 groups. Long PCR derived from clinical specimens
      was demonstrated to be applicable to RFLP analyses and sequencing without
      laborious test of virus isolation. Furthermore, the long PCR method described
      here will be useful for studies of the molecular epidemiology of VZV and for
      investigating variations among VZV isolates.

PMID- 12073571
TI  - [The current status of infectious enteritis in Japan--reports of the "Research
      Group for Infectious Enteric Diseases, Japan" in the last 5 years (1996-2000)].
AB  - The patients or carriers with infectious enteritis admitted to the Hospitals for
      infectious diseases in the last 5 years (1996-2000) were studied. The total
      number of cases admitted in each year were 969, 1,113, 981, 637 and 573
      respectively. A total of 1,527 Shigella spp. strains including 1,078 strains from
      overseas travelers' cases were isolated. The isolates of Salmonella spp.
      excluding S. Typhi and S. Paratyphi A were 562 in number. A total of 61 Vibrio
      cholerae O1 strains including 44 strains from overseas travelers was isolated.
      These V. cholerae O1 strains were all of El Tor type. Entamoeba histolytica,
      Giardia lamblia, Cryptosporidium parvum and Isospora belli were detected in 225,
      46, 3 and 3 cases respectively. Abdominal pain, nausea and vomiting were
      frequently observed in the cases caused by Vibrio parahaemolyticus. The highest
      body temperature and the highest frequency of bowel movements were revealed in
      the cases caused by Salmonella spp. Bloody stool was observed in 55.3% of the
      cases due to Escherichia coli, in 40.5% of the cases due to Campylobacter spp.
      and in 24.1% of cases due to Shigella spp. As for shigellosis and salmonellosis,
      the clinical symptoms were more serious in the domestic cases than those in
      travelers. OFLX-resistant strains accounted for 1.7% of Shigella spp. isolates.
      No strains of Salmonella spp. were resistant to OFLX. The incidence of drug
      resistant isolates of Campylobacter jejuni were 26.0% for OFLX and 2.5% for EM.

PMID- 12073572
TI  - [Practicability and reliability of a new rapid detection kit for rubella
      antibody].
AB  - We have investigated the practicability and reliability of a new rapid detection
      kit for rubella antibody by means of an immunochromatographic assay. This kit can
      measure 100 microliters of total blood or 50 microliters of serum or plasma in
      approximately 10 minutes. When a band appears in this kit, a sample is positive.
      The subjects of this investigation were 233 medical students or nursing students.
      Blood was also drawn from their fingertips of 71 of them. The blood was obtained
      with a lancet for measuring blood sugar. By an ELISA assay using IgG antibody for
      rubella, 188 samples (80.7%) were found to be positive, 1 sample (0.4%) was +/-,
      and 44 samples (18.9%) were negative. The positive IgG antibody titers deviated
      toward the lower levels since the median was lower than the mean. Therefore, the
      subjects were appropritate for evaluation of low titer samples. In comparison
      with the measurement of IgG antibody using the ELISA assay, the sensitivity and
      specificity levels of this new kit were 99.5% and 100%, respectively. The
      correlation index between the antibody titers and color concentration of the band
      was as weak as 0.5 (0.35-0.58 at 95% confident range). Seroconversion of the
      antibody in paired samples is necessary for diagnosis of rubella in this kit.
      However, if there is an uncertain past history of vaccination and/or rubella,
      this kit is useful for evaluating the need for vaccination in 10 minutes. It
      usually takes approximately one week to receive antibody results through a
      commercial laboratory.

PMID- 12073573
TI  - [Antimicrobial effects and efficacy on habitually hand-washing of strong acidic
      electrolyzed water--a comparative study of alcoholic antiseptics and soap and tap
      water].
AB  - The rate of bacterial elimination for the stamp method was compared with regular
      hand-washing (using soap and tap water), hygienic hand-washing (using alcoholic
      antiseptics), and hand-washing using strong acidic electrolyzed water (the SAEW
      method) in routine work. After routine work, the average number of bacteria
      remaining on the nurse's hands with using the SAEW-method, rubbing method and tap
      water method, were: 54 +/- 63, 89 +/- 190, 128 +/- 194 CFU/agar plate,
      respectively (n = 81). In this study. It was clarified that a much larger number
      of Bacillus sp. were detected for the rubbing method than for the other methods.
      After further nurse work, the most number of absorbed bacteria on a nurse's hands
      were counted after cleaning a patient's body. The rate of bacteria elimination
      for hand-washing with soap and tap water after taking care of a patient was
      insufficient, especially when before care was provided the number of bacteria on
      the nurse's hands were less than 100 CFU/agar plate. From these results, the
      following manual for sanitary hand washing is recommended: 1. At first, dirty
      hands should be cleaned and the number of bacteria should be reduced using soap
      and tap water or by scrubbing with disinfectants. 2. After the number of bacteria
      has been reduced, use the SAEW method routinely. 3. For care requiring a high
      level of cleanliness or if no tap water facilities are available, use the rubbing
      method. Finally, routine use of the SAEW method in ICU could be recommended with
      conventional disinfectants and soap and tap water on a case by case basis for
      less than adverse reactions, such as in the case of rough-hands or keeping a low
      level of bacteria on hands.

PMID- 12073574
TI  - [Microbiological evaluation of Helicobacter pylori stool antigen detection (HpSA)
      kit; its specificity and reactivity with coccoid form of H. pylori].
AB  - Helicobacter pylori stool antigen detection kit (HpSA) was microbiologically
      evaluated. All of the 10 strains of H. pylori showed positive result in HpSA
      test, but other bacteria of 16 species and 18 strains did not. In addition, the
      coccoid form of 10 H. pylori strains reacted positively with the HpSA kit as well
      as the helical form, although the OD450 value was slightly lower than that of
      helical form in 7 out of 10 strains examined. The minimum number of H. pylori
      showing positive reaction in HpSA test was 7.0 x 10(3) cfu. Feces of both
      conventional and germ free mice inhibited partially the reaction of H. pylori
      with HpSA kit, but this decrease in the reactivity was recovered by freeze
      thawing of the feces. In contrast, freeze-thawing of the mice feces with H.
      pylori decreased the sensitivity in HpSA test, but it was also shown that coccoid
      form had a stronger reactivity than helical form. These results indicate that the
      HpSA kit is a rapid and useful diagnostic method for detection of H. pylori,
      particularly its coccoid form, in the fecal specimens.

PMID- 12073575
TI  - [Pneumonitis with a bronchiolitis obliterans organizing pneumonia-like shadow in
      a patient with human herpes virus-6 viremia after allogeneic bone marrow
      transplantation].
AB  - We report the case of a 42-year-old male who underwent allogeneic bone marrow
      transplantation (BMT) for acute myelogenous leukemia, and then developed
      pneumonitis with a bronchiolitis obliterans organizing pneumonia (BOOP)-like
      shadow. When he came with exertional dyspnea four months after BMT, the chest X
      ray and CT findings disclosed bilateral infiltration, and remarkable elevation of
      his serum KL-6 level, a monitoring marker for disease activity in interstitial
      lung disease. Although organizing pneumonia (OP) was revealed by a transbronchial
      lung biopsy, no pathogen was detected in bacterial, fungal and routine viral
      cultures or by direct cytological examinations using bronchoalveolar lavage (BAL)
      specimens. Since human herpes virus-6 (HHV-6) was detected in BAL specimens by
      the polymerase chain reaction (PCR), a diagnosis of a pneumonitis-like BOOP
      shadow related to HHV-6 was made, and he was treated with methylprednisolone and
      ganciclovir (GCV). Although there was a relapse of his OP 1.5 months later, with
      re-elevation of his serum KL-6 level, continuous administration of GCV led to
      disappearance of HHV-6 in BAL specimens assayed by PCR, in association with
      normalization of the serum KL-6 level. HHV-6 should be considered as a cause of
      unexplained pneumonitis in BMT recipients, and KL-6 is useful for monitoring the
      pneumonitis status in these patients.

PMID- 12073578
TI  - [Mibyo (preventive medicine) in aged society].

PMID- 12073577
TI  - [A case of abrupt pulmonary infection by Rhizopus microsporus var.
      rhizopodiformis during treatment for bronchial asthma].
AB  - We presented a case of pulmonary Rhizops microsporus var. rhizopodiformis
      infection which developed abruptly during treatment of bronchial asthma by
      systemic corticosteroids. The patient, an 85 year-old-woman, was given systemic
      steroid therapy for 15 days. She suddenly became febrile two days after the
      therapy and was coughing up yellow sputum. Chest X-ray film showed multiple
      nodules with cavities which became worsened rapidly. A specimen of sputum culture
      gave a growth of Mucoraceae, which was identified to be Rhizopus microsporus var.
      rhizopodiformis. She was given amphotericin B and miconazole was added on the
      basis of MIC value of the strain. Although she improved initially, her clinical
      course showed neutropenia, pseudomembranous enterocolitis, malnutrition, and then
      died after about six months. Because the diagnosis of pulmonary mucormycosis is
      difficult and prognosis is poor, further studies for investigating clinical
      features would be necessary.

PMID- 12073576
TI  - [A successful treatment of Vibrio vulnificus infection].
AB  - A 65-year-old male patient with a history of alcoholism visited our outpatient
      clinic complaining of nausea and diarrhea followed by dizziness. Erythema and
      swelling with partial exfoliation on the right forearm to hand and right thigh
      were noticed. Vibrio vulnificus was isolated from the purulent discharge of the
      skin. Due to urgent and intensive treatment of bacterial shock and antimicrobial
      drugs, the patient fully recovered three months later. We believe that the
      patient survived from this fatal infection because; 1) the isolates were highly
      sensitive to a wide variety of antibiotics, 2) the antibiotic therapy was started
      immediately, with an alternative usage of different antibiotics, and 3) the liver
      dysfunction of the patient had not been severely damaged by alcohol before the
      infection.

PMID- 12073579
TI  - [Potential usefulness of hematopoietic stem cells in regenerative medicine].

PMID- 12073580
TI  - [Pressure ulcers in bedridden elderly subjects].

PMID- 12073581
TI  - [Diagnosis and treatment of the elderly patients with diabetes mellitus].

PMID- 12073582
TI  - [Silent cerebral infarction in elderly people].

PMID- 12073583
TI  - [New oxidized LDL receptors and their functions in atherogenesis].
AB  - Oxidized low density lipoprotein (Ox-LDL) appears to play key roles in
      atherosclerotic progression and plaque rupture. Biological effects of Ox-LDL on
      vascular cells may, at least in part, be mediated by cell surface receptors for
      Ox-LDL. Lectin-like oxidized LDL receptor (LOX)-1 and scavenger receptor for
      phosphatidylserine and oxidized lipoprotein (SR-PSOX) are type II and I membrane
      glycoprtoeins, respectively, both of which can act as cell-surface endocytosis
      receptors for atherogenic oxidized LDL (Ox-LDL). LOX-1 expression can dynamically
      be induced by proinflammatory stimuli, and is detectable in cultured macrophages
      and activated vascular smooth muscle cells (VSMC), in addition to endothelial
      cells. LOX-1-dependent uptake of Ox-LDL induced apoptosis of cultured VSMC. In
      vivo, endothelial cells that cover early atherosclerotic lesions, and intimal
      macrophages and VSMC in advanced atherosclerotic plaques dominantly express LOX
      1. LOX-1 expressed on the cellsurface can be cleaved, in part, and released as
      soluble molecules, suggesting the diagnostic significance of plasma soluble LOX-1
      levels. SR-PSOX appeared to be identical to CXCL16, a novel membrane-anchored
      chemokine directed to CXCR6-positive lymphocytes, suggesting another role of SR
      PSOX as T-cell chemoattractant. In contrast to LOX-1 expressed by a variety of
      cell types. SR-PSOX expression appeared relatively confined to macrophages in
      atherogenesis. Taken together, LOX-1 and SR-PSOX may play important roles in
      atherogenesis and athrosclerotic plaque rupture.

PMID- 12073584
TI  - [Free radical in Alzheimer's disease].

PMID- 12073585
TI  - [Antibiotic-associated colitis in senile patients].
AB  - Antibiotic-associated colitis (AAC) is a relatively frequent disorder in the
      senile population. Because of the change of life style in the elderly, the
      clinical pattern of AAC may be varied. The causative antibiotics, duration of
      administration, duration from taking antibiotics to onset of symptoms, background
      disorders, symptoms, laboratory data, therapies and prognosis in patients with
      AAC were investigated retrospectively in 54 cases of averaging 80.5 year old in
      this hospital. The patients with pseudomembranous colitis (PMC) are older and
      with a greater preponderance of female gender than patients with acute
      hemorrhagic colitis. Antimicrobial agents that frequently induced AAC are
      cephalosporins and penicillins. Symptoms in patients with PMC are diarrhea,
      abdominal cramping pain and fever. The most common background diseases were
      neurological and psychiatric disorders. Furthermore, recent advances in
      understanding the mechanism of toxin A-mediated colinic inflammation, and the
      management of AAC are reported.

PMID- 12073587
TI  - [Comprehensive geriatric assessment for elderly patients].

PMID- 12073588
TI  - [Early diagnosis, therapy, and long-term follow up of dementia].
AB  - Since the start of long term care insurance and the availability of
      cholinesterase inhibitor as a prescription drug in Japan, detection and diagnosis
      of dementia in the early stage of the disease has become an important issue.
      Neuropsychological screening and imaging tools usually employed for diagnosis are
      insufficient. The use of diagnostic criteria to designate early stage patients is
      still controversial. Several disease entities, including mild cognitive
      impairment (MCI) and age-associated memory impairment (AAMI), are not clearly
      defined in Japan. To study the prognosis of early stage dementia, it is important
      to define the diagnostic criteria. Clear identification and diagnosis of early
      stage dementia is important to support patients and their family members. The
      early detection of dementia and cognitive decline has other important aspects.
      One is the implication of disease diagnosis in the community; people often
      hesitate to use the name dementia in the early stage, even when the patients
      fulfill the criteria for dementia. Another aspect is the longer term follow up of
      the patients after early detection. For these purposes, it will become more
      important to emphasize a team approach consisting of medical doctors, nurses,
      neuropsychologists, clinical psychologists, occupational therapists and
      socialteam workers.

PMID- 12073586
TI  - [Trends geriatric disease research evaluated by long-term longitudinal study].
AB  - The number of patients with geriatric diseases will rapidly increase in our aging
      society. Geriatric diseases tend to progress chronically and disturb the daily
      activity of the elderly patients. Care for the elderly patients requires a great
      deal of manpower. The prevention and treatment of geriatric disease are urgent
      issues that must be addressed. A comprehensive longitudinal study of aging and
      geriatric disease was started at the National Institute for Longevity Sciences
      (NILS) in 1997. The participants of the NILS longitudinal study of aging (NILS
      LSA) were 2,267 men and women from a local community population. The participants
      are examined at the NILS and followed up every two years. An outline of the
      system and examinations of the NILS-LSA is shown. The latest results from the
      NILS-LSA research including geriatric disease-related genotypes and risk factors
      for mild cognitive impairment (MCI) are also presented.

PMID- 12073589
TI  - [Hormone replacement therapy and the diseases in the elderly].

PMID- 12073590
TI  - [Mechanisms of swallowing disorder in the elderly].

PMID- 12073591
TI  - [Differences in features between young-old and old-old patients beginning
      dialysis].
AB  - We investigated differences in features between young-old and old-old patients
      beginning dialysis. Patients aged over 60 years who had newly started dialysis
      (121 cases) were studied. These were 71 men and 50 women. The age was 74 +/- 7
      years (mean +/- standard deviation). The patients were divided into the young-old
      group (aged 60 to 74 years) and the old-old group (aged over 75 years), 64
      patients were young-old and 57 were old-old. In every patient, the cause of renal
      failure (non-diabetes/diabetes), body indexes, comorbid conditions, laboratory
      data of nutritional status, ambulation, cognitive function, and psychosocial
      status (acceptance of dialysis therapy, marital status, younger cohabitants, and
      engagement in work) were surveyed. Data were assessed in each group. Intergroup
      comparisons were made using Student's t-test, the chi 2 test, and the Mann
      Whitney's U-test. Diabetes was frequent in the young-old group. The results
      concerning body indexes, comorbid conditions, and laboratory data reflected age
      related phenomena or skew distribution of diabetic patients. Though differences
      were not statistically significant, both the percentage of patients with
      inability to walk and the percentage of patients with impaired cognitive function
      were lower in the old-old. These results could not be interpreted as age-related
      phenomena or skew distribution of diabetic patients. From the data of
      psychosocial indexes, it would speculate that the young-old had some advantage
      over the old-old for initiation of dialysis. We look for the explanation to
      psychosocial aspects of dialysis therapy.

PMID- 12073592
TI  - [Cardiovascular responses during bed-to-wheelchair transfers in frail elderly
      subjects living at home].
AB  - Cardiovascular responses during bed-to-wheelchair transfers were measured in 22
      frail elderly subjects (mean age, 79.7 years) and 11 healthy elderly subjects
      (mean age, 79.8 years) living at home. The frail elderly subjects were divided
      into two groups, based on the method of transfer: the dependent group consisted
      of 11 subjects who required additional help during all stages of the transfer,
      and the partially dependent or independent group consisted of 11 subjects who
      could perform the transfer with some help or independently. In the healthy
      elderly subjects, diastolic blood pressure increased significantly 15 minutes
      after the transfer compared to the pre-transfer measurement (p < 0.05). In the
      dependent group, there was no significant change in blood pressure, and mean
      blood pressure (MBP) decreased gradually after the transfer in 3 subjects. Only 4
      subjects exhibited a normal change in heart rate variability after the transfer.
      These results suggest the existence of poor cardiovascular responsiveness in most
      of these subjects. In the partially dependent or independent group, there was a
      significant increase in blood pressure just after the transfer (p < 0.05), in 3
      subjects, the blood pressure reached the WHO's defined hypertension threshold
      (SBP > 160 mmHg or DBP > 95 mmHg). In these subjects, performing the bed-to
      wheelchair transfer independently may result in cardiac overload. The change in
      MBP in the dependent group was significantly lower than that of the partially
      dependent or independent group from just before the transfer to 15 minutes after
      the transfer (p < 0.05). Blood pressure responses during bed-to-wheelchair
      transfers in frail elderly subjects living at home may differ according to the
      method of transfer.

PMID- 12073593
TI  - [Comparative effects of losartan and amlodipine on activities of sympathetic
      nerve, renin-angiotensin-aldosterone system and brain natriuretic peptide in the
      elderly hypertensive patients].
AB  - This study investigated the comparative effects of losartan and amlodipine on the
      activation of the sympathetic nervous system, renin-angiotensin-aldosterone
      system (R-A-A system) and brain natriuretic peptide (BNP) in patients with
      essential hypertension. Twenty-four elderly patients who had received more than
      12 months of antihypertensive treatment with amlodipine participated in this
      study. The treatment regimen of 5 mg/day amlodipine was changed to 50 mg/day
      losartan. Plasma catecholamines (norepinephrine, epinephrine and dopamine),
      active renin, aldosterone and BNP concentration were measured before and after an
      average of 5 months of losartan treatment. After losartan treatment, blood
      pressures were not changed, suggesting the comparable effect of 50 mg losartan
      and 5 mg amlodipine on elevated blood pressure. Losartan significantly reduced
      norepinephrine (799 +/- 277 pg/mL vs. 692 +/- 268 pg/mL, p < 0.05) and
      aldosterone concentration (81.2 +/- 35.3 pg/mL vs. 55.2 +/- 17.7 pg/mL, p <
      0.01), whereas there were not any changes in BNP concentrations. These findings
      suggested that losartan might be superior to amlodipine in prevention of chronic
      or intermittent sympathetic hyperactivity and enhanced R-A-A system.

PMID- 12073595
TI  - [A rare case illustrating the difficulty of diagnosing and treating elderly
      patient with CAPD-related peritonitis caused by the perforation of sigmoid colon
      diverticulum].
AB  - A 67-year-old man was admitted with abdominal pain on April 23, 2000. Continuous
      ambulatory peritoneal dialysis (CAPD)-related peritonitis was diagnosed.
      Administration of antibiotics for five days obtained no improvement. Therefore
      the peritoneal catheter was removed on April 28th. Although his condition became
      settled, C-reactive protein remained positive. Moreover, two kinds of bacilli
      were detected from the CAPD fluid, just before the catheter was removed. As
      abnormalities in the colon were possible, an enema examination was performed on
      May 23rd. A constriction and several diverticula of the sigmoid colon were
      detected. High grade fever appeared on May 23rd, and the patient complained of
      abdominal pain the next day. As there was no improvement, we performed enhanced
      computed tomography and detected an abscess in the Douglas pouch on May 29th. The
      abscess was resected on the same day, and he was discharged. The number of
      patients with chronic renal failure has increased in recent years. Although
      hemodialysis has been the treatment of choice, peritoneal dialysis should be
      considered. More investigations into complications created by peritoneal dialysis
      are required, especially in elderly people who seldom show symptoms of CAPD
      related peritonitis until they reach a critical condition. If peritoneal dialysis
      is being performed and inflammation reactions continue, it is necessary to
      examine the patient for perforated peritonitis and abscess formation.

PMID- 12073594
TI  - [Questionnaire on the attitude of the physicians in educating the elderly
      patients with chronic obstructive pulmonary disease about smoking cessation].
AB  - Smoking status, the extent of recognition of the relationship between smoking and
      COPD, and actual nature of education for smoking cessation by physicians have not
      yet been fully elucidated. To investigate perceptions about education for smoking
      cessation in the elderly by physicians who work in the clinic, questionnaires
      were sent to the 1,012 physicians who belong to the Yokohama City Medical
      Association. Of these, 311 respond and their data (31%) were included in the
      analysis. The questionnaire included questions on the importance of smoking
      cessation in the elderly, on the perception about the relationship between
      smoking and various diseases, and actual education for smoking cessation. The
      smoking status of the physicians themselves was also investigated. The
      distribution of current smokers, ex-smokers, and non-smokers among the physicians
      was 13%, 33%, and 54%, respectively. Seventy-five percent of ex-smokers answered
      that their experience of smoking cessation influenced their patient education for
      smoking cessation, and 39% of smokers answered that their smoking status did not
      influence it. Only 53% of the physicians replied that they actually performed
      education for smoking cessation to the elderly, and 8% of them replied that they
      hardly perform any or do not perform it. Smoking cessation is thought to be the
      only way to prevent the development of COPD. However, only a half of physicians
      recognized the importance of smoking cessation for the treatment and control of
      COPD in the elderly. In addition, less than one third of physicians perform
      nicotine replacement therapy for smoking cessation. Enlightenment for physicians
      should be needed to make them perform education for smoking cessation more
      aggressively.

PMID- 12073596
TI  - [A case of late onset mitochondrial neuromyopathy].
AB  - A 68-year-old woman was admitted with dysesthesia on both soles, hands and
      buttocks. She first noticed the dysesthesia in the left first toe two years
      before admission. One year before admission, serum creatine kinase and lactate
      dehydrogenase levels were elevated but she had no clinical symptoms suggesting
      myopathy. Nerve conduction study showed no apparent abnormalities, and an
      electromyogram showed mild myogenic change. Computed tomography of the muscle
      showed fatty degeneration of the trunk, major gluteus muscle, and biceps femoris
      muscle and atrophic change of the biceps femoris muscle. Muscle biopsy revealed a
      slight variation in fiber size, the presence of cytochrome c oxidase (CCO)
      negative fibers by CCO staining, ragged-red fibers by Gomori trichrome staining,
      and mild denervation fiber by neuron specific enolase (NSE) staining. Analysis of
      her mitochondrial DNA (mtDNA) revealed a large deletion of mtDNA (approximately
      8.5 Kb), and mitochondrial neuromyophy was diagnosed. The frequency of mtDNA
      deletion increases with aging. Although her mtDNA abnormality was compatible with
      chronic progressive external ophthalmoplegia (CPEO), we speculate that the aging
      process may be contributed to the mtDNA abnormality, which would be related to
      the late onset of her symptoms. As the phenotype of this mitochondrial disorder
      shows a wide variation and mtDNA abnormality is more frequent among elderly
      people, we should consider the possibility of mitochondrial disorders even in
      elderly people.

PMID- 12073597
TI  - [Guidelines on Treatment of Hypertension in the Elderly--2002 Revised Version].

PMID- 12073598
TI  - Outcome for malignant tracheobronchial stenoses in esophageal cancer.
AB  - OBJECTIVE: Optimal tracheobronchial stenosis treatment in esophageal cancer
      remains a clinical challenge. METHODS: Subjects were 26 patients with
      tracheobronchial stenosis due to esophageal cancer treated by modalities such as
      expandable metallic stent emplacement, laser therapy, radiotherapy, and/or
      chemotherapy. We assessed patient outcome and modality efficacy, and determined
      prognostic factors for survival using multivariate analysis. RESULTS: Of the 26,
      16 (61%) had improved respiration after treatment. Average posttreatment survival
      was 140 days (10-1550 days). Multivariate analysis indicated that a Karnofsky
      performance score of > or = 70% was the most significant prognostic factor, with
      chemotherapy and laser therapy also significant factors. CONCLUSIONS: Although
      individual modalities were effective in ameliorating respiratory symptoms,
      patients with good performance status survived the longest. After a
      tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy
      and laser therapy are recommended if the patient is in good general condition.

PMID- 12073599
TI  - Partial left ventriculectomy in pediatric end-stage dilated cardiomyopathy.
AB  - OBJECTIVE: Although a recent survey on pediatric cardiomyopathy in Japan showed
      that 48% of patients died despite the medical treatment, pediatric cardiac
      transplantation is not legal in Japan. We determined the feasibility of partial
      left ventriculectomy as an alternative to end-stage dilated cardiomyopathy.
      METHOD: We retrospective analyzed partial left ventriculectomy in 4 pediatric
      patients with end-stage dilated cardiomyopathy. RESULTS: In case 1, an 8-month
      old girl underwent semiemergency partial left ventriculectomy. Her ejection
      fraction increased from 10% to 25%, and her condition improved initially, but she
      developed heart failure and underwent cardiac transplantation 6 months later in
      the US. In case 2, a 3-year-old boy developed severe heart failure 2 months after
      ventricular septal defect repair. Intensive medical therapy failed, so partial
      left ventriculectomy was done, which increased his ejection fraction from 15% to
      35%. His condition is stable 35 months after surgery. In case 3, a 2-year-old
      girl with a chromosomal anomaly undergoing ventricular septal defect repair
      developed progressive heart failure 1 year later. Despite emergency partial left
      ventriculectomy, she died of hemoptysis 2 weeks postoperatively. In case 4, a 2
      year-old girl developing progressive heart failure unresponsive to medical
      therapy after 10 months underwent elective partial left ventriculectomy and
      remains in stable condition 18 months postoperatively. CONCLUSION: Partial left
      ventriculectomy is appropriate for selected patients with end-stage dilated
      cardiomyopathy if medical therapy is not effective and heart transplantation is
      not possible.

PMID- 12073600
TI  - Effects of chlorpromazine as a systemic vasodilator during cardiopulmonary bypass
      in neonates.
AB  - OBJECTIVES: Vasodilator use during cardiopulmonary bypass is important in
      pediatric cardiac surgery, but the full range of their effects on hemodynamics
      remains to be clarified. We studied the effects of chlorpromazine, a potent alpha
      blocking agent, in neonates. METHODS: Subjects were 60 neonates undergoing
      arterial switch operations for complete transposition of the great arteries with
      an intact ventricular septum. Of these, 37 received 2.1 to 6.5 mg/kg of
      chlorpromazine during cardiopulmonary bypass (CPZ group) and 23 received no
      vasodilator (control group). We then compared hemodynamic parameters between
      groups during and early after surgery. RESULTS: The systemic vascular resistance
      index and mean arterial pressure during cardiopulmonary bypass were significantly
      lower in the CPZ group (p < 0.05), but systolic pressure 15 minutes after
      cessation of cardiopulmonary bypass did not differ between groups. The rise in
      peripheral temperature during rewarming after hypothermia was significantly
      higher and the acid-base status 40 minutes after cardiopulmonary bypass less
      acidotic in the CPZ group. Urine output during cardiopulmonary bypass was higher
      in the CPZ group. CONCLUSIONS: Chlorpromazine effectively counteracts systemic
      vasoconstriction induced by cardiopulmonary bypass without serious side effects
      in neonatal cardiac surgery.

PMID- 12073601
TI  - Transparasternal transpericardial operation in the treatment of chronic empyema
      with bronchopleural fistula.
AB  - A 78-year-old man with a lung destroyed by chronic empyema underwent
      pleuropneumonectomy, 4 months after open-window thoracostomy, via a
      transparasternal transpericardial approach. This approach is safe and effective
      in great vessel and bronchus dissection and applicable to cases of persistent
      chronic empyema such as our.

PMID- 12073602
TI  - Active infective endocarditis due to methicillin-resistant Staphylococcus aureus
      in the acute phase of infectious mononucleosis.
AB  - A 26-year-old male was treated for acute hepatitis due to Epstein-Barr virus and
      infectious mononucleosis in our hospital. At 2 weeks after admission, there was
      relapse with high fever. A blood culture detected methicillin-resistant
      Staphylococcus aureus. A two-dimensional echocardiogram revealed severe aortic
      regurgitation and vegetation on the left coronary cusp of the aortic valve. The
      diagnosis was active infective endocarditis due to methicillin-resistant
      Staphylococcus aureus in the acute phase of infectious mononucleosis. Following
      preoperative administration of vancomycin, the aortic valve was replaced with a
      Carbomedics prosthetic valve. The aortic valve was bicuspid, and the right cusp
      and non-coronary cusp were conjoined. As the focus of infection was localized to
      the left coronary cusp, the infected tissue was fully removed with resection of
      all the cusps. Although fever persisted long after the operation, the blood
      culture became negative for methicillin-resistant Staphylococcus aureus, and
      repeated echocardiograms including transesophageal echocardiogram showed no
      prosthetic valve infection. Vancomycin was administered until the C-reactive
      protein became negative at 45 days after the operation.

PMID- 12073603
TI  - Primary liposarcoma of the mediastinum.
AB  - Primary mediastinal liposarcomas are extremely rare malignancies that remain
      asymptomatic until large and, even then, initial symptoms are nonspecific. We
      report a 48-year-old man followed up for asymptomatic multiple bullae who
      suffered progressive weight loss and dyspnea on exertion. Radiography and
      computed tomography of the chest showed a large mass with calcified nodules in
      the left pleural cavity and giant bullae in the right pleural cavity. Previous
      computed tomography of the chest showed a small tumor of mediastinal adipose
      tissue with calcified nodules. Tumor growth was calculated at about 500 times the
      tumor volume per 3.6 years. We completely resected the mediastinal tumor and
      conducted a bullectomy through a median sternotomy. The microscopic pathological
      diagnosis was well-differentiated/sclerosing liposarcoma. The man underwent no
      postoperative adjunctive irradiation and remains well 8 months after surgery.

PMID- 12073604
TI  - Aortic root replacements in reoperations.
AB  - We evaluated 4 patients who had undergone previous cardiac surgery underwent
      reoperation involving aortic root replacement. Subjects were a 55-year-old man
      who had undergone separate valve graft replacement for a dissecting aneurysm
      (DeBakey type I) 3.25 years earlier; a 51-year-old woman who had undergone
      separate valve graft replacement for a dissecting aneurysm (DeBakey type I) 6
      years earlier; a 66-year-old woman who had undergone aortic valve replacement and
      single coronary artery bypass grafting for severe aortic regurgitation, angina
      pectoris, and aortitis syndrome 11 years earlier; a 47-year-old man who had
      undergone mitral valve replacement and 3-coronary artery bypass grafting for
      severe mitral regurgitation and angina pectoris 4 years earlier. Development of a
      surgical technique, coupled with myocardial protection, and pharmacological
      treatment at reoperation yielded excellent early surgical results. To reduce the
      incidence of reoperation and ensure satisfactory long-term results, we recommend
      radical management for the individual case be selected at initial operation and
      entire resections be conducted for aneurysmal degeneration or dissected segments.

PMID- 12073605
TI  - Encapsulated thymoma metastasizing to a pectoralis major muscle.
AB  - An extensive review of the literature suggests that ours is the first case of
      encapsulated thymoma metastasizing to a skeletal muscle. A 43-year-old man
      underwent thymothymectomy for encapsulated Masaoka's stage I thymoma. Four years
      after complete resection, the tumor metastasized to the left pectoralis major
      muscle. Although a few reports exist on encapsulated thymoma metastasizing to a
      distant site, the literature does not describe encapsulated thymoma metastasizing
      to a skeletal muscle insofar as we could find.

PMID- 12073606
TI  - Primary aortoesophageal fistula secondary to thoracic aneurysm. Successful
      surgical treatment by extra-anatomic bypass grafting.
AB  - Aortoesophageal fistula (AEF) secondary to thoracic aneurysm is rare, and is
      usually fatal without prompt surgical intervention, with few survivors reported.
      Here we report a case of a 68-year-old woman late-presenting AEF successfully
      treated by extra-anatomic bypass grafting. Since she had already a mediastinal
      infection caused by AEF on admission, we performed extra-anatomic bypass grafting
      from the ascending aorta to the infrarenal aorta, and primary esophageal repair.
      The extra-anatomic bypass grafting was performed to avoid the risk to secondary
      graft infection and to decrease the total ishemic time induced by intraoperative
      aortic clamping, which is necessary when in-situ graft replacement is chosen.
      Although only 17 cases (including the present case) have been reported as long
      term survivors, most have involved in-situ repair of the thoracic aneurysm. To
      our knowledge, the present case was only the second treated successfully by extra
      anatomic bypass grafting. We recommend extra-anatomic bypass grafting for a case
      with severe infection and prolonged hypoperfusion insult caused by massive
      bleeding due to rupture in an aneurysm.

PMID- 12073607
TI  - Partial anomalous pulmonary venous connection of singular form.
AB  - We have recently experienced a rare case of partial anomalous pulmonary venous
      connection, in a 3-year-old female. The case was diagnosed preoperatively as
      anomalous left superior pulmonary venous connection with atrial septal defect.
      Surgery, however, revealed that only the right superior pulmonary vein returned
      to the left atrium, while the other three pulmonary veins returned to the
      coronary sinus or innominate vein. No associated atrial septal defect was found.
      An enlarged coronary sinus was observed. In the present case, three of the four
      pulmonary veins were found to have anomalous connections, and were
      hemodynamically close to being total anomalous pulmonary venous connection. We
      performed unique radical surgery using autologous tissue for multiple anomalous
      pulmonary venous connections and here report the results, with a short discussion
      of the literature.

PMID- 12073609
TI  - [X-chromosome inactivation].

PMID- 12073608
TI  - [LOX-1: the oxidized LDL receptor expressed in vascular endothelial cells].

PMID- 12073611
TI  - [Regulation of neurite formation by Rho family GTPases].

PMID- 12073610
TI  - [Roles of Eph receptors and the cell surface heparan sulfate proteoglycan
      syndecan-2 in dendritic spine morphogenesis].

PMID- 12073612
TI  - [Transcription factors regulating hematopoiesis: researches spanning from
      molecule to whole body].

PMID- 12073613
TI  - [LIM-kinases in actin cytoskeletal regulation and their physiological role].

PMID- 12073614
TI  - [Regulation of cellular phenotypes by Hic-5 that localizes both in the focal
      adhesion and in the nucleus].

PMID- 12073615
TI  - [Two-dimensional gel electrophoresis with agarose gels in the first dimension
      with wide applicability in analyzing various tissues and cells].

PMID- 12073616
TI  - [Clinical review of pneumothorax cases complicated with active pulmonary
      tuberculosis].
AB  - Pneumothorax is an important and dangerous complication of pulmonary
      tuberculosis. Forty-six pneumothorax cases complicated with active pulmonary
      tuberculosis at National Chiba-Higashi Hospital were studied retrospectively.
      From Jan. 1987 to Dec. 1997, we experienced 3611 patients with pulmonary
      tuberculosis, and among them 46 patients (18-90 years old, 38 males and 8
      females) had pneumothorax. On admission, 33 out of 46 cases (71.7%) were smear
      positive by sputum examination of mycobacteria and 41 out of 46 cases (89.1%) had
      cavitary lesions on chest X-ray. Eleven cases had mild pneumothorax, thirty-two
      had moderate, and three had severe. Pneumothorax was present on admission in 23
      patients and developed during treatment for tuberculosis in the other 23
      patients. Eleven patients were treated with bed rest alone, four were
      thoracentesis and aspiration, twenty-four were intrathoracic tube drainage and
      seven were operated. Thirty-one patients were recovered, but fifteen passed away,
      among them 13 due to respiratory failure. The Prognostic nutritional index (PNI;
      10 x serum albumin concentration +0.005 x peripheral lymphocyte count) which was
      proposed by Onodera, serum albumin level and Body mass index were lower in the
      fatal group than in the survival group. We consider these indices are useful to
      evaluate the prognosis of active tuberculosis patients complicated with
      pneumothorax.

PMID- 12073617
TI  - [An outbreak of pulmonary tuberculosis probably due to exogenous reinfection at a
      nursing home for the elderly].
AB  - In Japan and other countries where tuberculosis is not so common, people who were
      once infected with tuberculosis are thought to rarely suffer from the disease
      again due to exogenous reinfection. We experienced a mass outbreak of
      tuberculosis with 27 patients (including the source of infection) at a nursing
      home for the elderly. Epidemiological investigation suggested that the source of
      infection was an 82-year-old woman resident. For about 2 years before this
      outbreak, she had complained of a productive cough. At the time of the diagnosis
      of tuberculosis, chest radiography revealed a cavitary lesion and a smear of her
      sputum revealed organisms rated as Gaffky No. 8. Sputum culture was also positive
      (++++). Of the 27 patients, 19 (including the source) underwent restriction
      fragment length polymorphism (RFLP) analysis of isolates from the sputum.
      Eighteen patients showed an identical RFLP pattern, indicating that the infection
      had arisen from one source. Out of all patients, the source case of infection, 9
      others with the same RFLP pattern, and other 3 who did not undergo RFLP analysis
      were admitted to our hospital. In 12 patients (3 men and 9 women excluding the
      source case) aged 80.6 years (range: 67-89 years), chest radiography disclosed
      tuberculous lesions, and smears, the polymerase chain reaction, and culture of
      sputum demonstrated Mycobacterium tuberculosis. As the prevalence of tuberculosis
      infection in Japanese aged 80 years at the time of the mass outbreak (1995) was
      presumed to be about 80%, the disease seemed to be caused by exogenous
      reinfection in most of these patients. All of the patients had senile dementia
      and other complications, and they were bedridden and undernourished. Anemia,
      hypoalbuminemia and lymphocytopenia were also observed in most of the cases.
      Malnutrition due to these complications appeared to be a possible risk factor of
      tuberculosis caused by exogenous reinfection.

PMID- 12073619
TI  - [Thymoma complicated with miliary tuberculosis].
AB  - We report a case of thymoma complicated with miliary tuberculosis. A 69-year-old
      woman was admitted to a hospital because of body weight loss, general fatigue,
      and dyspnea. Chest X-ray showed a small, diffuse granular shadows in both lungs.
      Biopsied-specimens from bone marrow and left pharynx revealed granuloma with both
      giant cells and caseous necrosis. The diagnosis of miliary tuberculosis was made.
      The patient was then transferred to our hospital. Both chest X-ray and computed
      tomography conducted on admission revealed a mass in the mediastinum as well as
      diffuse granular shadows in both lungs. We suspected a presence of thymoma. Anti
      tuberculosis therapy was started, and extended thymectomy was performed. The
      diagnosis of thymoma was confirmed pathologically. Immunological analysis of
      peripheral blood lymphocytes was done before and after the operation. Negative
      conversion of PPD reaction was observed after thymectomy. Although the response
      of peripheral lymphocytes to phytohaemoagglutinin (PHA) and concanavalin A
      recovered after thymectomy, a marked decrease of the number of CD 4 T cells, a
      decrease of T helper 1 cells, a slight increase in the number of B cells and
      cells expressing natural killer cell-related surface markers were observed
      throughout the course of illness.

PMID- 12073618
TI  - [Longitudinal assessment of IFN-gamma production in patients with pulmonary
      tuberculosis complicated with diabetes mellitus].
AB  - Patients with diabetes mellitus (DM) are more susceptible to bacterial infection
      including pulmonary tuberculosis. To define the immunopathologic mechanisms
      underlying pulmonary tuberculosis in patients with DM, the production of IFN
      gamma by CD4+ T cells or PBMC were followed up longitudinally during
      antituberculous chemotherapy. At the time of diagnosis, IFN-gamma production by
      CD4+ T cells in either tuberculosis patients without DM (TB) or with DM was
      significantly lower than that in the healthy control. CD4+ T cells in
      tuberculosis patients with DM under poor control (DM(p)TB) produced significantly
      less IFN-gamma than did patients with DM under good control (DM(g)TB). In
      longitudinal studies, IFN-gamma production in both TB and DM(g)TB patients
      returned to the control level by 6 months, whereas the production in DM(p)TB
      patients remained depressed. There was no significant relation between regimens
      of antituberculous chemotherapy and the production of IFN-gamma by PBMC in all
      subject groups. IFN-gamma production was depressed in DM(p)TB patients treated
      with HREZ for 6 months. These results indicate that depressed production of IFN
      gamma in DM(p)TB patients is prolonged not due to tuberculous infection but
      intrinsic defect presumably induced by poorly controlled DM.

PMID- 12073620
TI  - [A case of pulmonary infection caused by Mycobacterium szulgai].
AB  - We report a case of pulmonary non-tuberculous mycobacteriosis caused by
      Mycobacterium szulgai. A thirty-nine-year-old man with no relevant significant
      past history underwent an annual medical check. His chest X-ray and CT scan
      showed an infiltrative shadow with a cavity in the right upper lobe. As it was
      suggestive of pulmonary tuberculosis, he was referred to our hospital. Smear
      tests of his sputum, gastric fluid, and transbronchial fluid showed no
      mycobacterial organisms, but culture of the samples revealed growth of
      mycobacteria. The organism was identified as M. szulgai using a DNA-DNA
      hybridization method, and the case was diagnosed as pulmonary non-tuberculous
      mycobacteriosis caused by M. szulgai. By anti-mycobacterial drug treatment with
      isoniazid, rifampicin, and ethambutol, the infiltrative shadow on chest
      roentogenogram and CT showed improvement. Culture of his sputum and gastric fluid
      showed no growth of mycobacteria after starting treatment.

PMID- 12073622
TI  - [Diabetic nephropathy].

PMID- 12073621
TI  - [Pulmonary infection caused by Mycobacterium szulgai: a case report].
AB  - We reported a case of pulmonary infection caused by Mycobacterium szulgai (M.
      szulgai) in an immunocompetent, asymptomatic 55-year-old man without underlying
      disease. A chest radiograph of an annual health examination revealed a right
      upper lobe infiltrate with thin-walled cavities, which was not present in the
      previous year. An acid-fast stain of bronchial washing fluid was positive, and
      antimycobacterial chemotherapy with isoniazid (400 mg/day), rifampin (450
      mg/day), and ethambutol (750 mg/day) was initiated on presumptive diagnosis of
      the case as tuberculosis. DNA-DNA hybridization of sputum and bronchial washing
      samples identified M. szulgai as the causative organism. Antimicrobial
      susceptibility testing indicated that the isolate was sensitive to most common
      antimycobacterial drugs except capreomycin (CPM) and p-aminosalicylic acid (PAS),
      and was also sensitive to clarithromycin and fluoroquinolones including
      ofloxacin, levofloxacin, sparfloxacin, and ciprofloxacin. After 12 months of
      therapy, a repeat chest radiograph demonstrated improvement of the right upper
      lobe infiltrate. When M. szulgai is isolated, it almost always represents a true
      pathogen. Therefore, the detection of even a small number of M. szulgai warrants
      treatment based on susceptibility testing.

PMID- 12073623
TI  - [Shear stress-induced platelet aggregation in children with minimal change
      nephrotic syndrome].
AB  - Analysis of the hemostasis system using biochemical techniques in children with
      minimal change nephrotic syndrome (MCNS) has previously been restricted to in
      vitro assays. The recent introduction of measurement of shear stress-induced
      platelet aggregation (SIPA) using platelet-rich plasma (PRP) has facilitated
      detailed investigation of the hemostatic system in vivo. In order to further
      analyze the etiology of the thrombotic tendency exhibited by patients with
      childhood MCNS, we investigated SIPA at both low shear stress (L-SIPA) and high
      shear stress (H-SIPA) in 14 children with MCNS using PRP collected weekly after
      commencing prednisolone therapy. Seven patients were newly diagnosed cases of
      MCNS (ND) whereas the remainder had suffered a disease relapse (DR). Prior to
      prednisolone therapy L-SIPA, which was thought to be affected by fibrinogen (Fbg)
      levels, was significantly increased in both patient groups compared to normal
      controls (17.4 +/- 4.1% vs. 3.6 +/- 0.7%, ND vs control, p < 0.01: 11.7 +/- 3%
      vs. 2 +/- 0.7%, DR vs control, p < 0.01) with values declining at weekly
      intervals thereafter. Plasma Fbg levels in simultaneously collected samples
      followed a similar course. In contrast, H-SIPA, which was thought to be affected
      by von Willebrand factor (VWF), was significantly enhanced in MCNS patients after
      1 week of prednisolone therapy compared to the controls (45 +/- 5.1% vs. 26.3 +/-
      3.5%, ND vs normal, p < 0.05: 36.9 +/- 3.3% vs. 25.5 +/- 1.6%, DR vs. normal, p <
      0.05). Plasma ristocetin cofactor and VWF antigen levels in simultaneously
      collected samples followed a similar course, whereas thrombin-antithrombin
      complex (TAT) levels remained constant. These results indicate that SIPA is
      enhanced in the acute stage of childhood MCNS, especially L-SIPA prior to the
      initiation of prednisolone therapy and H-SIPA after 1 week of prednisolone
      therapy, and that these phenomena may be affected by plasma Fbg and VWF levels,
      respectively. The enhanced SIPA may play an important thrombogenic role in the
      acute phase of childhood MCNS.

PMID- 12073624
TI  - [Significance of parenteral iron administration for HCV-positive hemodialysis
      patients].
AB  - BACKGROUND: It is well recognized that parenteral iron administration is
      recommended for hemodialysis (HD) patients treated with rHuEPO. On the other
      hand, hepatic iron concentration increases in chronic hepatitis C, and iron
      reduction improves serum transaminase levels in these patients. METHODS: We
      compared the rHuEPO doses with hematological parameters in HCV-positive (n = 7)
      and HCV-negative (n = 32) HD patients when parenteral low-dose iron was
      administered for one year (target ferritin level: 200-300 ng/ml, target
      hematocrit level: 30-33%). RESULTS: None of the parameters was significantly
      different between the groups at the start of the study. One year later, levels of
      hematocrit and serum ferritin significantly increased compared with those at the
      start in each group (HCV-positive group: 28.0 +/- 2.7-->31.3 +/- 1.5%, p < 0.01,
      119.3 +/- 171.9-->303.3 +/- 77.7 ng/ml, p < 0.05, respectively, HCV-negative
      group: 26.8 +/- 2.2-->30.0 +/- 3.5%, p < 0.01, 69.8 +/- 100.5-->278.4 +/- 66.4
      ng/ml, p < 0.01, respectively). Serum transaminase levels were not significantly
      different between the start and end points in the HCV-positive group, but 2
      patients showed an increase in these levels. In the HCV-negative group, the
      rHuEPO dose at the end point was significantly reduced compared with that at the
      start (4,875 +/- 2,089-->4,031 +/- 2,203 IU/W, p < 0.05). In the HCV-positive
      group, however, it was difficult to reduce the rHuEPO dose in order to maintain
      the target hematocrit level (4,071 +/- 1,134-->3,857 +/- 1,464 IU/W, NS).
      CONCLUSION: We suggested that rHuEPO should be used together with parenteral iron
      administration, even in HCV-positive HD patients, because it is safe at low doses
      under careful observation.

PMID- 12073626
TI  - [Effects of fluvastatin on plasma lipid abnormalities in hemodialysis patients
      with chronic renal failure].
AB  - Fluvastatin, an HMG-CoA reductase inhibitor, was administered at a dosage of 20
      mg/day for 24 weeks to 11 hemodialysis patients with a high plasma total
      cholesterol (TC) level (> or = 220 mg/dl). Serum lipids, apolipoprotein, and
      malondialdehyde (MDA) levels were measured every 12 weeks. After 24 weeks of
      fluvastatin administration, the TC level had decreased by 10.5% (238 +/- 15 mg/dl
      ->203 +/- 25 mg/dl), the low density lipoprotein cholesterol (LDL-C) level had
      decreased by 16.2% (142 +/- 32 mg/dl-->119 +/- 26 mg/dl), and the HDL-C level had
      increased by 23.4% (47 +/- 15 mg/dl-->58 +/- 19 mg/dl). These changes were
      statistically significant and resulted in a reduction of the atherogenic index
      (AI: TC-HDL-C/HDL-C). The triglyceride (TG) level did not change significantly.
      The apolipoprotein A1 level increased by 9.1% (121 +/- 22 mg/dl-->132 +/- 20
      mg/dl) and the apolipoprotein B level decreased by 20.2% (114 +/- 25 mg/dl-->91
      +/- 20 mg/dl). The MDA level also decreased significantly (1.16 +/- 0.92 nmol/ml-
      >0.58 +/- 0.38 nmol/ml). No particular side effects were observed during the 24
      weeks of fluvastatin administration. In conclusion, fluvastatin may play an
      important role in preventing significant oxidative stress and was shown to be
      safe and effective in reducing the TC, LDL-C, MDA and AI levels in dialysis
      patients with hypercholesterolemia. The possibility that this improvement in the
      plasma lipid profile of dialysis patients may decrease atherogenic complications
      requires further investigation, including long-term clinical observations.

PMID- 12073625
TI  - [Long-standing high-transport membrane as a risk factor for EPS development after
      PD withdrawal: an analysis based on changes in peritoneal function during and
      after CAPD withdrawal].
AB  - The pathophysiology of encapsulating peritoneal sclerosis (EPS) that develops
      after withdrawal from long-standing dependence on CAPD remains unclear. The aim
      of this study was to clarify the risk factors for EPS as expressed in the
      peritoneal function. Fourteen patients who had shifted to standard hemodialysis
      after long-term CAPD (average, 105 months) were studied: 3 developed EPS after PD
      withdrawal while 11 did not. Analysis of the data obtained from the peritoneal
      equilibration test (PET) revealed that: (1) the dialysate/plasma creatinine ratio
      (D/Pcr) was significantly higher in the EPS group than in the non-EPS group
      during the course of PD as well as after PD withdrawal; and (2) eight patients,
      including the 3 with EPS, were classified as being in a high-transport membrane
      state (HTS) at PD withdrawal. The duration of HTS during PD was longer in those
      patients with EPS. During the periods after PD withdrawal, none of these EPS
      patients recovered from HTS, whereas 4 of the 5 non-EPS patients did. These data
      suggest that long-standing HTS during the course of PD as well as post
      withdrawal, may be risk factors for EPS development. For this reason, it is
      indicated that PET has clinical relevance in examining sequential changes in
      peritoneal function and in detecting those patients at risk of EPS.

PMID- 12073627
TI  - [A case of secondary hyperparathyroidism with an ectopic intrathyroid gland
      successfully diagnosed and controlled by percutaneous ethanol injection therapy
      (PEIT)].
AB  - Secondary hyperparathyroidism (II HPT) is a major complication in chronic
      dialysis patients, and percutaneous ethanol injection therapy (PEIT) has become a
      useful alternative treatment for II HPT. However, the existence of ectopic
      parathyroid glands is a major problem when conducting PEIT. Ectopic parathyroid
      gland accepts 10-35% of II HPT, and the missing glands cannot be detected
      consistently by any imaging techniques, including scintigraphy. Intrathyroid
      parathyroid gland is as rare as about 1% and recurrence of missing glands after
      parathyroidectomy (PTx) has been reported in some cases. We report here a 52-year
      old female in whom an ectopic parathyroid gland was defected successfully and
      intact-PTH controlled by tentative PEIT. At the first examination, a left
      parathyroid adenoma and a right thyroid goiter were pointed out by
      ultrasonography, CT and scintigraphy. PEIT was applied twice to the left
      parathyroid adenoma, but intact-PTH was not decreased. Ultrasonography, CT, 201Tl
      99mTc subtraction scintigraphy and fine needle aspiration biopsy (FNAB) were
      performed again to search for the existence of ectopic glands. The results
      suggested that the right intrathyroid tumor was an ectopic parathyroid gland.
      Consequently, tentative PEIT was applied to the right intrathyroid tumor, and
      successful control of intact-PTH and serum Ca was eventually achieved. To our
      knowledge, this is the first reported case of secondary hyperparathyroidism with
      an ectopic intrathyroid gland that was successfully controlled by PEIT. In this
      case, it was suggested that tentative PEIT of intrathyroid tumor was a useful
      method for detecting an ectopic parathyroid gland.

PMID- 12073628
TI  - [Interstitial nephritis induced by mesalazine].
AB  - This report concerns the first case in Japan of interstitial nephritis induced by
      mesalazine, a new therapeutic agent for inflammatory bowel disease, such as
      ulcerative colitis. Twenty-two cases have already been reported in other
      countries. The patient, a 27-year-old woman, was treated with mesalazine for her
      ulcerative colitis at another hospital. At the beginning of her treatment, her
      serum creatinine level was within the normal range. After 12 months, this level
      increased up to 5.7 mg/dl. She was then referred to our hospital for renal
      investigation and therapy. A renal biopsy revealed that severe tubulo
      interstitial nephritis had occurred. Her mesalazine treatment was withdrawn and
      prednisolone was administered. Her serum creatinine level decreased gradually.
      However, this level remained at about 2.8 mg/dl and stabilized at that level. She
      was then discharged from the hospital. Glomeruli appeared to have minor
      glomerular abnormalities except for one globally sclerosed glomerulus as observed
      by light microscopy. However, IgM and C3 deposition on glomeruli were also
      observed. Glomerular lesions were suspected from these histological findings. A
      similar case that showed IgM. C3 depositions in glomeruli has previously been
      reported. The possibility of glomerular lesions being induced by mesalazine
      should be further researched. From the summary of reported cases, a delay of
      diagnosis of interstitial nephritis induced by mesalazine has resulted in
      permanent irreversible renal failure. Intensive monitoring of renal function is
      required when a patient is treated with mesalazine.

PMID- 12073629
TI  - [Sibling cases of nephritis resembling membranoproliferative glomerulonephritis].
AB  - We have experienced rare cases of membranoproliferative glomerulonephritis (MPGN)
      like nephritis, which was seen in siblings. Both the brothers had asymptomatic
      hematuria and proteinuria at an age before 10, 7 and 4 years old, respectively.
      Renal biopsy revealed proliferative glomerulonephritis, resembling MPGN type III.
      The family history showed that their father and grandfather suffered from end
      stage renal disease, suggesting that MPGN seen in the present sibling cases is
      hereditary. A review of the literature revealed that familial MPGN is rare, that
      most of the cases have urinary abnormalities at an age of less than 10 years, and
      that male preponderance is seen in familial MPGN.

PMID- 12073630
TI  - [Current status of nuclear medicine clinical application of FDG-PET for cancer
      diagnosis. Lung cancer].
AB  - Recent advances in small cyclotrons, PET scanners, and image-processing software
      have made it possible to apply FDG-PET for clinical use, especially for tumor
      imaging. Although the efficacy of FDG-PET for several tumors remains a problem
      under discussion, the efficacy of PET for lung cancer has been studied in great
      detail and has already been established. The roles of FDG-PET for lung cancer
      management are, roughly speaking, 1) characterization of pulmonary nodules, 2)
      staging of lung cancer, 3) monitoring therapeutic effect, and 4) early diagnosis
      of tumor recurrence. We examined the usefulness of FDG-PET for lung cancer by
      analyzing our own data and reviewing recent reports. Two image-processing
      techniques, the image fusion technique and the respiratory-gated data-acquisition
      method, are also introduced in this article. FDG-PET is a promising method of
      anatomical imaging that is complementary to such techniques as CT and MRI. It may
      obtain a more important position among imaging modalities in the future.

PMID- 12073631
TI  - [Current status of nuclear medicine clinical application of FDG-PET for cancer
      diagnosis. Head and neck cancer].
AB  - Accurate detection of head and neck cancer is crucial in patients' quality of
      life. The head and neck area consists of many complicated anatomical structures.
      Conventional imaging procedures such as CT and MRI provide much detailed
      information, but accurate estimation of the spread of cancer is still limited.
      Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose (FDG) is
      clinically useful in detecting head and neck cancer, providing accurate estimates
      of head and neck primary cancer especially in cases that are equivocal on CT
      and/or MRI. FDG-PET is able to show metastatic lymph nodes that may appear normal
      on CT and/or MRI. Further, whole body FDG-PET makes it possible to detect distant
      metastases. The clinical usefulness of FDG-PET in head and neck cancer is
      discussed in this review.

PMID- 12073632
TI  - [Current status of nuclear medicine. Clinical application of FDG-PET for cancer
      diagnosis. Esophageal cancer].
AB  - Positron emission tomography (PET) with [18F]-fluorodeoxyglucose (FDG) is a tool
      for the imaging and evaluation of glucose metabolism. This technique has recently
      become available in more than thirty hospitals and has been approved under
      Japan's national health insurance program. FDG uptake correlates with glucose
      utilization in tissue and is widely used for evaluating malignant tumors as well
      as brain function and myocardial viability. FDG-PET is useful for the diagnosis
      of lung cancer, colon cancer, esophageal cancer, malignant lymphoma, malignant
      melanoma, head and neck cancer, myocardial viability, and epileptic focus. A
      brief summary of the application and utility of FDG-PET for esophageal carcinoma
      is described in this article. Because of its limited spatial resolution, FDG-PET
      is not able to evaluate the invasiveness of primary tumors and small lesions.
      However, the uptake of FDG correlates with the aggressiveness of the tumor and
      the prognosis of patients with esophageal carcinoma. The sensitivity,
      specificity, and accuracy of lymph node staging is higher than that with CT. FDG
      PET has the advantage of being able to detect distant metastases on a single
      occasion. Evaluation of the response to therapy and of recurrence is also
      possible by means of FDG-PET. There is some normal uptake and physiological
      distribution of FDG in many organs. Physiological status has an effect on the
      uptake of FDG in normal organs, and, consequently, on lesion uptake.
      Understanding of these characteristics makes this procedure a useful diagnostic
      modality for the management of patients with esophageal carcinoma.

PMID- 12073633
TI  - [Current status of nuclear medicine. Clinical application of FDG-PET for cancer
      diagnosis. Colorectal cancer].
AB  - In Japan, colorectal cancer is the third most common cause of death from cancer.
      The recurrence rate after curative surgical treatment for colorectal cancer has
      been estimated at 30-40%, most frequently occurring within 3 years. Therefore,
      more accurate staging of recurrent colorectal cancer is required for more
      appropriate management decisions. This article focuses on the clinical value of
      PET with [18F]fluorodeoxyglucose (FDG) in the diagnosis of recurrent and primary
      colorectal cancers. The technical issues in clinical practice and the cost
      effectiveness of FDG-PET in staging recurrent colorectal cancer will be covered.

PMID- 12073634
TI  - [Current status of nuclear medicine. Clinical application of FDG-PET for cancer
      diagnosis. Malignant lymphoma].
AB  - Malignant lymphoma is one of the tumors that show high FDG uptake, enabling the
      accurate detection of small involved lesions by FDG-PET. It is useful in both
      initial staging and follow-up study. In initial staging, FDG-PET is superior to
      CT from the aspects of sensitivity and specificity, and it is reported that the
      therapeutic protocol has been changed in 21% of patients. In the follow-up of
      therapy and detection of recurrence, the accuracy of residual disease is reported
      to be more than 90%. Among the different pathological types of lymphoma,
      Hodgkin's disease and intermediate-grade NHL are typical indications because of
      the requirement of accurate staging in determining the therapeutic protocol. One
      of the shortcomings of FDG-PET is its low specificity. Combination study with PET
      tracers with higher specificity in tumor diagnosis such as C-11 methionine or F
      18 methyltyrosine could be a way to solve this problem.

PMID- 12073635
TI  - [An experimental study for tumor detection by indocyanine green with near
      infrared topography].
AB  - We studied tumor detection by indocyanine green (ICG) with near-infrared
      topography in rat experimental tumors: hepatoma AH109A and osteosarcoma POB 102.
      Time-intensity curves and topograms after ICG injection were obtained in tumors
      and surrounding normal tissues. Intensities in tumors were slowly reduced, and
      intensities in normal tissues were rapidly reduced, resulting in positive tumor
      image in topogram. It is concluded that near-infrared topography enhanced by ICG
      is useful for cancer detection.

PMID- 12073636
TI  - [Evaluation of PROPELLER MR imaging: preliminary experiences].
AB  - Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction
      (PROPELLER) MR imaging (MRI) has a unique ability to correct motion artifacts and
      is expected to be useful in diffusion-weighted MRI. This article describes
      preliminary experiences with PROPELLER MRI. PROPELLER uses a radial scan
      variation of the fast spin-echo sequence and it shows much less spatial
      deterioration than the echo-planar imaging sequence. To determine the optimal
      parameters of this technique, we calculated the signal intensities of phantoms
      and brains in various settings. PROPELLER MR examinations were also performed in
      66 patients for clinical use. PROPELLER MRI appears to be a promising and useful
      technique.

PMID- 12073637
TI  - [Development of picture and voice gated intermittent irradiation system connected
      without linear accelerator for voluntary breath-hold synchronized with
      respiration].
AB  - In patients with lung cancer of the lower lobes and liver cancer, treatment
      volume including respiratory motion is an important therapeutic problem. We
      developed a voluntary breath-hold system using pictures and voice messages so as
      to reduce the excessive safety margin that covers respiratory motion. The system
      consists of two sets of monitor and speaker, and a computer and software for
      control without direct connection to a linear accelerator. When the patient
      repeatedly holds his or her breath in response to a picture and voice message,
      irradiation is manually performed and then proceeds intermittently. Although
      safety problems remain to be solved because of off-line, synchronized irradiation
      with our system is simple, inexpensive, and could be widely used. It also would
      be expected to reduce the tumor target volume around the diaphragm.

PMID- 12073638
TI  - [Calcium phosphate bioceramics in orthopedic implants].

PMID- 12073639
TI  - [Marginal indications for the Magerl method of fixation of C1-C2 (case report)].
AB  - The authors present a 4-year old girl who had a car accident as a passenger and
      hurt her head, chest and limbs as well as upper cervical spine. The patient with
      multiple injuries was taken to the FTN Centre of Children's traumatology, Prague.
      Here the basic vital functions were ensured and a diagnosis was made of contusion
      of the brain with quadriparesis and inhibition of the respiratory centre,
      contusion of the chest, epiphysiolysis of the distal femur and later also
      instability of C1-C2. A censor for measuring or intracranial pressure was
      immediately inserted with a subsequent reduction of the distal femur and elastic
      fixation. External lumbar drainage was performed in the next week instability of
      C1-C2 was not found out and therefore not treated. Three months after the injury
      a ventriculoperitoneal shunt for intracranial hypertension was inserted. MRI
      showed stenosis in the region of occipitocervical passage and dorsal
      decompression of craniocervical passage was performed which consisted in the
      removal of the posterior arch of C1 and a significant extension of foramen magnun
      dorsally and laterally to both sides. Due to persisting ligamentous instability
      of C1-C2 with a spastic quadriparesis and inhibition of the respiratory centre a
      surgical atlantoaxial stabilization was indicated, i.e. causal treatment of
      instability. Seven months after the injury Magerl fixation of C1-C2 was performed
      by 2.7 mm titanicum screws (Synthes). Preoperative stability of C1-C2 in the
      reduced position was satisfactory but with regard to iatrogenic instability the
      C0-C1 fixation was combined with occipitocervical fussion by Ransford loop
      extending over C0-C3. Further, the triangular flap of periost was overturned from
      the external occipital protuberance to C3 and all this was bridged by cortical
      cancellous bone grafts from iliac crest. After two months a check simple and
      functional x-ray examination showed a stable fusion of C0-C2. The neurological
      finding remained the same even after one year, i.e. a severe quadriparesis with
      the inhibition of the respiratory centre requiring artificial lung ventilation.

PMID- 12073640
TI  - [The Essex-Lopresti forearm fracture (case report)].
AB  - The radial head fracture associated with dislocation in the distal end of the
      ulna and tear of interosseous membrane of the forearm with a subsequent proximal
      migration of the radial shaft is a relatively rare injury. For the first time it
      was described by Essex-Lopresti in 1951. Our report presents one case together
      with an analysis of available literature relating to the diagnosis and treatment.
      A man, 69 years old, hurt his right elbow and forearm in a fall on the
      outstretched arm. There was a 2 x 1 cm excoriation on the lateral portion of the
      elbow and a dominating pain and limitation of the range of motion of the right
      elbow and wrist. The radiograph of the elbow, forearm and wrist showed a
      dislocated comminuted fracture of the radial head, dorsal subluxation of the
      ulnar and proximal displacement of radius. The condition was assessed as Essex
      Lopresti fracture of the forearm indicated for surgery. The four-fragment
      fracture of the radial head did not allow reconstruction and therefore the head
      was resected. Subsequently the distal radio-ulnar joint was revised from dorsal
      approach with a K-wire inserted transversally. In order to prevent proximal
      displacement of the radius a K-wire was inserted in the medullary cavity of the
      radius close to the distal end of the humerus with the elbow in 90 degrees
      flexion and slight supination. The wounds were sutured and plaster of Paris
      applied extending across the elbow up to the metacarpal heads. After 6 weeks the
      plaster fixation and K-wires were removed. Full weight bearing was permitted 4
      months after the surgery. Ten months after the surgery the patient was without
      complaints. Flexion in the elbow ranged between 0-5-130 degrees, pronation
      supination was limited by 10 degrees in both extreme positions. The ulnar head
      became prominent on the dorsal side, dorsiflextion and ulnar duction in the wrist
      were limited to 10 degrees. The radiograph of the wrist showed and evident
      proximal displacement of the radius, the dorsally subluxated ulnar head overhung
      by 7 mm. Our case has confirmed that a mere extirpation of the head with a
      subsequent stabilization and transfixation of the proximal end of the radius and
      transfixation of the distal radio-ulnar joint cannot prevent after the extraction
      of wires a proximal displacement of the radius and development of the "plus
      variant" resulting in the limitation of both the range of motion of the wrist and
      the pronation-supination movement of the forearm.

PMID- 12073641
TI  - [Mini-invasive treatment of purulent spondylitis associated with a psoas abscess
      in a child (case report)].
AB  - The authors describe a case of a 12 years old boy who suffered from pain in the
      lumbar region, limitation of dynamics in lumbosacral spine with a gradual
      deterioration of the condition. The patient was afebrile. The pain was getting
      worse and the classic radiographs did not show at the beginning any pathological
      changes. Suspected were mainly the discogenic syndrome, functional vertebrogenous
      syndrome but also development of a tumour in the region of spine. CT scan
      revealed structural changes in the region of L3 vertebra and less in the L4
      region. At the same time it showed a soft mass pushing the psoas muscle to the
      left which was described as paravertebral abscess and the structural changes as a
      suspect L3, L4 spondylitis. The condition of the patient was associated with a
      high risk of endocarditis as in the childhood he underwent the Senning operation
      for coarctation of great vessels. Therefore it was necessary to determine
      etiological agent as quickly as possible. After a mini-invasive surgery with a
      probational biopsy and subsequent drainage the spondylytis was confirmed also
      histologically and a coagulation-negative Staphylococcus aureus was cultivated as
      an etiological agent. At the same time tumour development was eliminated. After
      15 weeks the antibiotic therapy was changed as after the removal of drains the
      microbe was already resistant to the administered antibiotics and therefore the
      antibiotics were changed with regard to sensitivity and minimum inhibition
      concentrations. Within 15 weeks after a local drainage by antibiotics and the
      total antibiotic therapy also inflammation markers gradually decreased and the
      patient is for a long period without complaints with full range of motion in the
      lumbosacral spine. In the conclusion the authors emphasize the accurate timing
      algorithm of the diagnosis in children which may initiate an early and successful
      treatment.

PMID- 12073642
TI  - [Periosteal desmoid].
AB  - The authors describe a rare benign disease occurring in children and adolescents
      with an increased physical activity at the age of 8-20 years. It is a tumour-like
      lesion developed by a repeated micro-trauma of the origin of distal fibres of
      adductor magnus and aponeurotic origin of the medial head of the gastrocnemius.
      This disease must be paid increased attention as in the region of the knee joint
      in children it is a location of a frequent development of sarcoma and
      osteomyelitis. With the knowledge of this lesion such cases may be diagnosed
      merely by a classic radiograph, preferably in external rotation and CAT and MRI
      examinations. Of the highest value for the examination is the CAT examination.
      Radiograph changes are located in the region of the distal part of the medial
      crest of linea aspera, tuberculum adductorium and posteromedial part of the
      medial epicondyle of femur.

PMID- 12073644
TI  - [The Bone and Joint Decade, 2000-2010. Global economic burdens and health care
      needs associated with diseases of the musculoskeletal system].

PMID- 12073645
TI  - [Use of the elastic stable intramedullary nailing technique in non-typical
      pediatric fractures].
AB  - PURPOSE OF THE STUDY: The "Elastic Stable Intramedullary Nailing" (E.S.I.N.) of
      French authors as a method of treatment of children's diaphyseal long bone
      fractures is well known from nineties of the last century. After we got familiar
      with the technique we wanted to introduce it in other indications, especially
      some metaphyseal long bone fractures and injuries of metacarpals, meta-tarsals
      and phalangeal bones in the growing skeleton. MATERIAL: During two last years,
      i.e. 1999-2000, ESIN procedure in 97 children was performed in our Regional
      Pediatric Trauma Centre. That was 39% of all osteosyntheses and 3.05% of all
      children's fractures treated during this period. Children treated by ESIN
      procedure were divided into three groups (see in Methods), 52 being in group one,
      28 in group two and 17 in group three. METHODS: In our series of patients managed
      with the use of ESIN procedure according to the type of fractured bone and
      physical behavior of the implants three groups were formed. In the first group
      called "Classic ESIN Procedure" were children with diaphyseal long bone fracture
      (femur, tibia, humerus and forearm bones), in the second group "Non-typical ESIN
      Procedure" metaphyseal long bone fractures (humerus, radius, tibia) and in the
      third group, "ESIN-like Procedure" patients with metacarpal and phalangeal
      digital fractures were included. In all children the technique was very similar
      to original French (Nancy) description. Supraphyseal trepanation of the bone and
      introduction of usually two prebent elastic nails intramedullary. RESULTS: All 97
      children healed good. In four children we saw little problems. In one patient it
      was necessary to change the ESIN osteosynthesis of open tibia fracture to
      external fixation. In the other boy we saw delayed union of forearm bones and in
      the third a 2 centimeter overgrowth of the affected tibia was recorded. In the
      last boy where non-typical ESIN procedure was performed for proximal radial
      fracture separation the angulation of radial head, overgrowth and subluxation
      occurred. However, we were surprised by simplicity, short time of the procedure
      and good results in two new groups of patients with metaphyseal and metacarpal
      resp. phalangeal fractures. DISCUSSION: Though in metaphyseal long-bone fractures
      (Non-typical ESIN Procedure) and metacarpal and phalangeal digital fractures
      (ESIN-like Procedure) the technique does not respect original physical
      suggestions of three point fragment fixation it works very well. Already the
      French authors from Nancy mention the indication of the ESIN technique for some
      metaphyseal fractures (supracondylar humeral and proximal radial). We do not use
      the method in supracondylar fractures but found it excellent in earlier
      problematic proximal humeral and radial fractures and especially phalangeal
      digital fractures. Also we were able to establish three main indication groups
      for this procedure. CONCLUSIONS: The ESIN technique can be used in three groups
      of children's fractures. "Classic ESIN Procedure" in diaphyseal long bone
      fractures, "Non-typical ESIN Procedure" in metaphyseal long bone fractures and
      "ESIN-like Procedure" in metacarpal and phalangeal digital fractures.

PMID- 12073646
TI  - [Distal shortening osteotomy of the metatarsals using the Weil technique:
      surgical treatment of metatarsalgia and dislocation of the metatarsophalangeal
      joint].
AB  - PURPOSE: Weil technique of the distal shortening osteotomy of metatarsal is a
      relatively new method of the surgical treatment of metatarsalgia and dislocation
      of metatarsophalangeal (MTP) joints. A retrospective study evaluates the first
      experience in Weil osteotomy at the authors' department. MATERIAL: Between May
      1999 and the end of 2000 twelve patients (14 feet) were operated on in which the
      Weil technique of the osteotomy was performed on 28 metatarsals. Indication for
      the surgery was chronic metatarsalgia with dislocation of the MTP joint, with
      excessive length of one or more lesser metatarsals, with insufficiency of the
      first ray after the surgery of hallux valgus and metatarsalgia after the
      resection of the head of II metatarsal. All patients were women, average age of
      57 years (range, 50-68 years) at the time of operation. The average follow-up is
      9 months (range, 6-24 months). Dislocated prior to operation were 9 MTP joints,
      in 2 cases a deformity of 2nd digit of the digitus supraductus type was operated
      on. METHODS: The patients evaluated subjectively the functional and cosmetic
      outcomes of the surgery. Clinical evaluation related to recurrence or transfer of
      difficulties to the head of the neighbouring metatarsal, range of motion of the
      MTP joint, function and grip of the digit. Radiograph was used for the evaluation
      of the metatarsal index, post-operative shortening of II metatarsal, reduction of
      dislocation in the MTP joint and healing of osteotomy. RESULTS: Satisfied with
      the functionla and cosmetic results of the operation were 83% patients (10 of
      12). Recurrence of metatarsalgia was not found in any patient,
      transfermetatarsalgia in one patient. Reduction of the range of motion in the MTP
      joint (plantar flexion) by more than 50% was recorded in 43% operated on
      metatarsals and in all metatarsals after the reduction of the dislocation.
      Acceptable function and strength of the digit evaluated by the ability to press
      by the digit a sheet of paper against the floor was preserved in most of the
      operated on metatarsals--86% (24 of 28). Average shortening of II metatarsal was
      5.6 mm. All dislocated MTP joints were reduced postoperatively. Dislocation
      recurred in 2 cases. Avascular necrosis of the head of II metatarsal after the
      reduction of the dislocation was encountered in one case. DISCUSSION: The small
      number of recurrences and transfermetatarsalgia proves that Weil osteotomy
      allowing a controlled shortening of metatarsal with a fixation is a reliable
      method in the solution of metatarsalgia. The operation directly on the joint
      allows reduction of the dislocation of the MTP joint. Shortening of metatarsal
      facilitates reduction and reduces axial pressure in the MTP joint. Recurrence of
      dislocation is reported between 15% and 22%. After a more difficult reduction and
      danger of redislocation some authors recommend a temporary transfixation of the
      MTP joint by K-wire. The disadvantage of the operation is a frequent temporary
      limitation of the range of motion in the MTP joint which is caused by the opening
      of the articular capsule and its subsequent contraction. No author reports any
      problems with the healing of the osteotomy. The results in our group of patients
      are comparable with the results published by other authors. CONCLUSION: Weil
      osteotomy allows a planned controlled shortening of metatarsal with a stable
      fixation. Osteotomy heals well. Osteotomy is intraarticular which on one side
      provides the possibility to correct dislocation in the MTP joint, however, on the
      other hand it poses a risk of the limitation of the range of motion of this
      joint. The main contribution the authors see in the new possibility of surgical
      treatment of more severe matatarsalgia and deformities of the forefoot with the
      preservation of joints.

PMID- 12073647
TI  - [Reconstructive surgery of the peripheral nerves in the upper extremities with
      autografts].
AB  - PURPOSE OF THE STUDY: The author presents results of 42 surgeries performed by
      microtechnique in 42 patients within the treatment of 45 nerves in the period of
      15 years, i.e. between 1985 and 1999. MATERIAL: Forty-five nerves were
      reconstructed in 42 patients with a lesion of peripheral nerves of upper limbs by
      means of autografts. METHOD: The efficiency of the surgery was analyzed on the
      basis of the following indicators: the interval between the injury and surgery,
      the patient's age, length of autograft, nature of injury, level of injury, type
      of the injured nerve. In the evaluation we used Sedon's classification of motor
      and sensitive functions of 1975. RESULTS: The best results were achieved in young
      patients up to the age of 20, in timely operations within 3 months, in nerve
      grafts up to the length of 5 cm. A simple cut wound provides much better
      conditions for a successful auto-transplantation of a nerve graft as compared to
      other more complicated injuries (e.g. lacerated wound or contusion). CONCLUSIONS:
      A timely surgical revision combined with neurolysis and, if need be, with a
      reconstruction surgery is in indicated cases a decisive factor influencing the
      outcome of the surgery.

PMID- 12073648
TI  - [Clinical examination of menisci in the era of arthroscopy].
AB  - PURPOSE OF THE STUDY: A profound clinical history and examination in case of a
      soft-tissue injury of the knee joint has a principal significance for the
      diagnosis and the following treatment. Our aim was to compare the development of
      surgery of the soft-tissue injury of the knee in our region within a 25-year
      interval. The most frequently affected structures in the knee joint are the
      menisci. We have focussed on the evaluation of the extent to which selected
      clinical history and symptoms are actually associated with the affection of
      menisci. MATERIAL: First we compared groups of patients operated on for the soft
      tissue injury of the knee joint within a 25-year interval. The scope of the care
      in the out-patient department was in this period almost the same. Then we
      examined a group of patients with a suspect tear of menisci and focussed on the
      clinical history and findings which are most often related to the injuries of
      menisci. METHODS: In a retrospective study aimed at the acquisition of sufficient
      statistical data and concentrated on the development of the surgery of the soft
      tissue knee we compared a group of 91 patients operated on by arthrotomy in the
      period of 1973-1975 with a group of 780 patients operated on in the years 1996-98
      by arthroscopy. In the subsequent prospective study we examined 104 patients sent
      to arthroscopic examination for a suspect tear of the medial or lateral meniscus.
      Based on the performed arthroscopy we divided the patients into three group--with
      the injured medial meniscus, with the injured lateral meniscus and without
      affection of meniscus. We investigated the diagnostic value of clinical history
      and clinical symptoms. RESULTS: In the retrospective study comparing the groups
      of patients in the 25-year interval the number of knee joints operated on
      increased 9times, the average age decreased by 8 years and the duration of
      hospitalisation was reduced by 9 days, the period of after-treatment in the out
      patient department was reduced by 59 days. In the prospective study focussed on
      the lesion of meniscus the success rate of clinical history and examinations was
      62% in lesions of the medial meniscus, 47% in lesions of the lateral meniscus.
      Significant in the clinical history of both menisci was a joint effusion and
      click phenomenon in the knee joint. Of clinical symptoms relating to lesion of
      the medial meniscus there often (above 60%) occurred pain of the medial joint
      line, painful bend and positive Steinmann II test, in case of the lateral
      meniscus painful bend and inability of full bend (nebo flexion--co ma autor na
      mysli terminem "dotazeni?) and walking in bend. Their disadvantage is a low
      specificity. On the contrary lower sensitivity but higher specificity is recorded
      by the clinical history of the locked knee and the presence of click phenomena
      during clinical examination. Simultaneous affection of the cartilage of the
      medial condyle of the femur in the lesion of the medial meniscus was in 64% of
      cases and of the lateral condyle of the femur in the lesion of the lateral
      meniscus in 47% of cases. DISCUSSION: Opinion on the clinical history and
      examination of the injured knee joint has not changed substantially during 25
      years as shown by the comparison of the literature, but arthroscopy thanks to its
      visualisation of the joint cavity and a lower invasiveness contributed to the
      improvement of the diagnostics of the lesions of the knee joint, a less invasive
      surgery resulting in a reduced period of treatment. As compared to other authors
      we achieved in the evaluation of clinical history and examination practically the
      same success rate of diagnosis in the lesion of the medial meniscus but a lower
      success rate in the lesion of the lateral meniscus. As concerns clinical history
      we did not find any significant differences in comparison with other authors, in
      case of clinical examination we did not achieve such good results in case of
      McMurray test and as the most significant manoeuvre we consider the Steinmann II
      test for the medial meniscus. Frequent simultaneous injury of the cartilage and
      menisci corresponds to the findings of other authors. CONCLUSION: Indication for
      surgery for the affection of menisci therefore has to be based on a careful
      analysis of clinical history and examination of the patient, it is not possible
      to rely on any of the menisci symptoms and their significance is only supportive.
      As the most significant symptoms we assess the clinical history of the verified
      knee swelling, click phenomena and locked knee in the knee joint, in the clinical
      examination pain and click phenomena of the joint lines.

PMID- 12073649
TI  - [Diagnosis of heart contusions].
AB  - PURPOSE OF THE STUDY: Heart contusion is a severe injury for the diagnosis of
      which there still doesn't exist a uniform procedure. The aim of the work was to
      compare individual methods and provide opinion on the justification of their use.
      MATERIAL: In the period of 1998-2000 at the authors' departments 103 patient were
      hospitalised with a severe contusion of the chest. These patients were admitted
      at the department within 24 hours after the injury. METHODS: The diagnosis was
      based on the examination of the ratio of CKMB/CK serum levels, cTnl serum level,
      ECG examination and echocardiography. RESULTS: Heart contusion was diagnosed in
      18 patients of the group of 103. The most precise diagnostic method proved to be
      the determination of the serum level of troponin I (success rate 86%) and
      echocardiographic examination (succes rate 67%). CONCLUSIONS: Examination of cTnl
      serum level and echocardiography are the best methods for the determination of
      the diagnosis of heart contusion. Simultaneous application of these two methods
      is the most reliable diagnostic procedure. Examination of CK and CKMB serum
      levels produces often falsely positive results and it is not a contribution to
      the determination of the diagnosis of heat contusion.

PMID- 12073650
TI  - [Diagnostic arthroscopy of the wrist in adults and children with subsequent
      single-stage surgical procedures].
AB  - INTRODUCTION: Wrist arthroscopy today still faces the problem of being much to
      often diagnostic only. In addition, if the diagnosis requires a larger operation
      to follow, it can rarely be performed in the same session. Above all the special
      positioning makes a second session necessary. A new technique of wrist
      arthroscopy established in the University Clinic of Basel, Switzerland, allows a
      conventional positioning and thus a secondary surgical procedure in the same
      session. In a prospective clinical two-centre study, we aim to answer questions
      about general feasibility and possible complications due to the multiple
      compartment anatomy in adults and children. MATERIAL AND METHODS: In the two
      centres, University Clinic for Hand Surgery Basel, Switzerland and Orthopaedic
      Clinic IPVZ Hospital Bulovka, Czech Republic, we perform the new technique of
      wrist arthroscopy without distraction. Conventional 2.4 mm arthroscope and the
      III/IV, VI/R and MCU--approaches were used in adult patients (n = 147) and
      children (n = 10). High pressures up to 150 mm Hg of Ringer's lactate solution
      replaced the traction, but leaving the wrist freely movable and in a comfortable
      horizontal position. If indicated by the diagnostic arthroscopy, an open
      operation on the wrist was performed immediately. A standardised regimen of
      previously arranged clinical controls was followed. RESULTS: Out of 157 wrist
      arthroscopies performed in the two clinics, 32 had an arthrotomy or another
      surgical procedure to follow in the same session. The mean duration of the
      diagnostic arthroscopy was 34 minutes. There were no arthroscopy related
      complications. Also in children, the arthroscopy gave the sufficient information
      about wrist anatomy and it was possible to continue with the surgical procedure
      in the same session. DISCUSSION: According the literature reports, the arthrotomy
      does not follow the wrist arthroscopy using distraction, because the complicated
      positioning of the extremity. Wrist arthroscopy without distraction is a new
      technique, previously published by first author, and enables arthrotomy of the
      wrist in the same session, and was not previously published. Also arthroscopy of
      the wrist in the childhood was not published up to now. CONCLUSIONS: In our study
      we have proven the feasibility of an arthrotomy or another surgical procedure to
      follow an arthroscopy on the wrist, all despite the special anatomical situation
      and the high intraarticular fluid pressure. We conclude the overall cost to be
      reduced and the patient's comfort improved. The method of the wrist arthroscopy
      without distraction can be used also in the childhood.

PMID- 12073651
TI  - Microarray analysis of bacterial pathogenicity.
AB  - The DNA microarray, a surface that contains an ordered arrangement of each
      identified open reading frame of a sequenced genome, is the engine of functional
      genomics. Its output, the expression profile, provides a genome wide snap-shot of
      the transcriptome. Refined by array-specific statistical instruments and data
      mined by clustering algorithms and metabolic pathway databases, the expression
      profile discloses, at the transcriptional level, how the microbe adapts to new
      conditions of growth--the regulatory networks that govern the adaptive response
      and the metabolic and biosynthetic pathways that effect the new phenotype.
      Adaptation to host microenvironments underlies the capacity of infectious agents
      to persist in and damage host tissues. While monitoring the whole genome
      transcriptional response of bacterial pathogens within infected tissues has not
      been achieved, it is likely that the complex, tissue-specific response is but the
      sum of individual responses of the bacteria to specific physicochemical features
      that characterize the host milieu. These are amenable to experimentation in vitro
      and whole-genome expression studies of this kind have defined the transcriptional
      response to iron starvation, low oxygen, acid pH, quorum-sensing pheromones and
      reactive oxygen intermediates. These have disclosed new information about even
      well-studied processes and provide a portrait of the adapting bacterium as a
      'system', rather than the product of a few genes or even a few regulons. Amongst
      the regulated genes that compose this adaptive system are transcription factors.
      Expression profiling experiments of transcription factor mutants delineate the
      corresponding regulatory cascade. The genetic basis for pathogenicity can also be
      studied by using microarray-based comparative genomics to characterize and
      quantify the extent of genetic variability within natural populations at the gene
      level of resolution. Also identified are differences between pathogen and
      commensal that point to possible virulence determinants or disclose evolutionary
      history. The host vigorously engages the pathogen; expression studies using host
      genome microarrays and bacterially infected cell cultures show that the initial
      host reaction is dominated by the innate immune response. However, within the
      complex expression profile of the host cell are components mediated by pathogen
      specific determinants. In the future, the combined use of bacterial and host
      microarrays to study the same infected tissue will reveal the dialogue between
      pathogen and host in a gene-by-gene and site- and time-specific manner.
      Translating this conversation will not be easy and will probably require a
      combination of powerful bioinformatic tools and traditional experimental
      approaches--and considerable effort and time.

PMID- 12073652
TI  - How oxygen damages microbes: oxygen tolerance and obligate anaerobiosis.
AB  - The orbital structure of molecular oxygen constrains it to accept electrons one
      at a time, and its unfavourable univalent reduction potential ensures that it can
      do so only with low-potential redox partners. In E. coli, this restriction
      prevents oxygen from oxidizing structural molecules. Instead, it primarily
      oxidizes reduced flavins, a reaction that is harmful only in that it generates
      superoxide and hydrogen peroxide as products. These species are stronger oxidants
      than is oxygen itself. They can oxidize dehydratase iron-sulphur clusters and
      sulphydryls, respectively, and thereby inactivate enzymes that are dependent upon
      these functional groups. Hydrogen peroxide also oxidizes free iron, generating
      hydroxyl radicals. Because hydroxyl radicals react with virtually any
      biomolecules they encounter, their reactivity is broadly dissipated, and only
      their reactions with DNA are known to have an important physiological impact. E.
      coli elaborates scavenging and repair systems to minimize the impact of this
      adventitious chemistry; mutants that lack these defences grow poorly in aerobic
      habitats. Some of the growth deficits of these mutants cannot be easily ascribed
      to sulphydryl, cluster, or DNA damage, indicating that important aspects of
      oxidative stress still lack a biochemical explanation. Obligate anaerobes cannot
      tolerate oxygen because they utilize metabolic schemes built around enzymes that
      react with oxidants. The reliance upon low-potential flavoproteins for anaerobic
      respiration probably causes substantial superoxide and hydrogen peroxide to be
      produced when anaerobes are exposed to air. These species then generate damage of
      the same type that they produce in aerotolerant bacteria. However, obligate
      anaerobes also utilize several classes of dioxygen-sensitive enzymes that are not
      needed by aerobes. These enzymes are used for processes that help maintain the
      redox balance during anaerobic fermentations. They catalyse reactions that are
      chemically difficult, and the reaction mechanisms require the solvent exposure of
      radicals or low-potential metal clusters that can react rapidly with oxygen.
      Recent work has uncovered adaptive strategies by which obligate anaerobes seek to
      minimize the damage done by superoxide and hydrogen peroxide. Their failure to
      divest themselves of enzymes that can be directly damaged by molecular oxygen
      suggests that evolution has not yet provided economical options to them.

PMID- 12073653
TI  - Drug resistance in yeasts--an emerging scenario.
AB  - In view of the increasing threat posed by fungal infections in immunocompromised
      patients and due to the non-availability of effective treatments, it has become
      imperative to find novel antifungals and vigorously search for new drug targets.
      Fungal pathogens acquire resistance to drugs (antifungals), a well-established
      phenomenon termed multidrug resistance (MDR), which hampers effective treatment
      strategies. The MDR phenomenon is spread throughout the evolutionary scale.
      Accordingly, a host of responsible genes have been identified in the genetically
      tractable budding yeast Saccharomyces cerevisiae, as well as in a pathogenic
      yeast Candida albicans. Studies so far suggest that, while antifungal resistance
      is the culmination of multiple factors, there may be a unifying mechanism of drug
      resistance in these pathogens. ABC (ATP binding cassette) and MFS (major
      facilitator superfamily) drug transporters belonging to two different
      superfamilies, are the most prominent contributors to MDR in yeasts. Considering
      the abundance of the drug transporters and their wider specificity, it is
      believed that these drug transporters may not exclusively export drugs in fungi.
      It has become apparent that the drug transporters of the ABC superfamily of S.
      cerevisiae and C. albicans are multifunctional proteins, which mediate important
      physiological functions. This review summarizes current research on the molecular
      mechanisms underlying drug resistance, the emerging regulatory circuits of MDR
      genes, and the physiological relevance of drug transporters.

PMID- 12073654
TI  - The physiology and collective recalcitrance of microbial biofilm communities.
AB  - Microbial biofilms impinge upon all aspects of our lives. Whilst much of this
      impact is positive, there are many areas in which the presence and activities of
      biofilms are regarded as problematic and in need of control. It is in this
      respect that biofilms reveal their recalcitrance towards many of the long
      established antibiotics, and industrial and medical treatment strategies. The
      nature of the resistance of biofilms, in spite of much research, remains an
      enigma. Whilst it is recognized that reaction--diffusion limitation properties of
      the biofilm matrix towards the majority of treatment agents will impede access,
      this cannot be the sole explanation of the observed resistance. Rather, it will
      delay the death of cells within the community to various extents. Similarly, it
      is recognized that biofilm communities are phenotypically heterogeneous and that
      their eradication will reflect the susceptibility of the most resistant
      phenotype. The nutrient and gaseous gradients that generate this heterogeneity
      will, however, be destroyed as a result of antimicrobial treatments and cause the
      phenotype of the survivors to alter from slow-growing resistant cells to fast
      growing susceptible ones. Accordingly both explanations can only delay death of
      the community. In order to explain more fully the long-term recalcitrance of
      biofilms towards such a wide variety of biocidal agents, more radical hypotheses
      must be considered. Amongst these are that multidrug efflux pumps could be up
      regulated on expression of a biofilm phenotype. Whilst this is an appealing and
      simple explanation, because of its ability to explain the breadth of agents to
      which biofilms are resistant, recent work has suggested that this is not the
      case. Alternative hypotheses attempt to explain the diversity of agents by
      invoking a common cause of death for which singular resistance mechanisms could
      be applied. It is therefore suggested that an altruistic majority of sublethally
      damaged cells in a population commit suicide (apoptosis), thereby providing some
      protection to the survivors. A proportion of cells (persisters) is suggested to
      be defective, or repressed, in their suicide response, and survive. The
      persisters thereby benefit from the self-sacrifice of their compatriots and
      maintain the gene pool. A second explanation of the presence of persisters is
      that the general stress response, well known to include the adoption of a viable,
      nonculturable state of quiescence, is up-regulated in small pockets of the
      biofilm community, where nutrients are particularly scarce. Such quiescent cells
      noted for their resistance towards the metabolically acting biocides would
      potentially have their dormancy broken after treatment by the replenished supply
      of nutrients caused by the death of the majority. A more recent hypothesis
      suggests that extracellular signals, 'alarmones', released from killed cells
      might prime recipients into a state of resistance. Thus, in biofilm communities
      deep lying cells might be alerted into a resistant state by the premature death
      of peripheral cells. It is equally possible that 'alarmones', in this context,
      are merely the post-treatment 'wake-up' call to a previously quiescent subset of
      cells. In this review, we attempt to provide a holistic view of the potential
      mechanisms by which biofilms express resistance. Since these mechanisms are
      multifaceted then their impact upon resistance will be considered against the
      context of biofilm formation, growth and maturation.

PMID- 12073655
TI  - Biochemistry, regulation and genomics of haem biosynthesis in prokaryotes.
AB  - Haems are involved in many cellular processes in prokaryotes and eukaryotes. The
      biosynthetic pathway leading to haem formation is, with few exceptions, well
      conserved, and is controlled in accordance with cellular function. Here, we
      review the biosynthesis of haem and its regulation in prokaryotes. In addition,
      we focus on a modification of haem for cytochrome c biogenesis, a complex process
      that entails both transport between cellular compartments and a specific
      thioether linkage between the haem moiety and the apoprotein. Finally, a whole
      genome analysis from 63 prokaryotes indicates intriguing exceptions to the
      universality of the haem biosynthetic pathway and helps define new frontiers for
      future study.

PMID- 12073657
TI  - The extracytoplasmic function (ECF) sigma factors.
AB  - Bacterial sigma (sigma) factors are an essential component of RNA polymerase and
      determine promoter selectivity. The substitution of one sigma factor for another
      can redirect some or all of the RNA polymerase in a cell to activate the
      transcription of genes that would otherwise be silent. As a class, alternative
      sigma factors play key roles in coordinating gene transcription during various
      stress responses and during morphological development. The extracytoplasmic
      function (ECF) sigma factors are small regulatory proteins that are quite
      divergent in sequence relative to most other sigma factors. Many bacteria,
      particularly those with more complex genomes, contain multiple ECF sigma factors
      and these regulators often outnumber all other types of sigma factor combined.
      Examples include Bacillus subtilis (7 ECF sigma factors), Mycobacterium
      tuberculosis (10), Caulobacter crescentus (13), Pseudomonas aeruginosa
      (approximately 19), and Streptomyces coelicolor (approximately 50). The roles and
      mechanisms of regulation for these various ECF sigma factors are largely unknown,
      but significant progress has been made in selected systems. As a general trend,
      most ECF sigma factors are cotranscribed with one or more negative regulators.
      Often, these include a transmembrane protein functioning as an anti-sigma factor
      that binds, and inhibits, the cognate sigma factor. Upon receiving a stimulus
      from the environment, the sigma factor is released and can bind to RNA polymerase
      to stimulate transcription. In many ways, these anti-sigma:sigma pairs are
      analogous to the more familiar two-component regulatory systems consisting of a
      transmembrane histidine protein kinase and a DNA-binding response regulator. Both
      are mechanisms of coordinating a cytoplasmic transcriptional response to signals
      perceived by protein domains external to the cell membrane. Here, I review
      current knowledge of some of the better characterized ECF sigma factors, discuss
      the variety of experimental approaches that have proven productive in defining
      the roles of ECF sigma factors, and present some unifying themes that are
      beginning to emerge as more systems are studied.

PMID- 12073656
TI  - Global adjustment of microbial physiology during free radical stress.
AB  - Oxidation can damage all biological macromolecules, and the survival of a cell
      therefore depends on its ability to control the level of oxidants. Microbes
      possess an astonishing variety of antioxidant defences, ranging from small,
      oxidant-scavenging molecules to self-regulating, homeostatic gene networks. Most
      often these antioxidant defences are activated by exposure to specific classes of
      oxidants. Interestingly, the isolation of pleiotropic mutations that impair or
      exacerbate the expression of subsets of oxidant-responsive genes led to the
      identification of global regulators. In a few, well-characterized cases, these
      regulators can transduce oxidative damage into gene regulation. Recently, the
      application of genomic tools to study the antioxidant responses of E. coli has
      both confirmed previous observations and provided evidence for a wealth of
      putative new anti-oxidant functions. Here, we review the remarkable diversity of
      antioxidant defence mechanisms, with emphasis on signal transduction by global
      regulator proteins and the corresponding genetic networks that protect the
      microbial cell against oxidative stress.

PMID- 12073658
TI  - [Clinical presentation and diagnosis of diabetic neuropathy].
AB  - Autonomic and sensory nerve dysfunction are progressive forms of diabetic
      neuropathies, often accompanied by other microvascular complications which are
      usually characterized by gradual onset of symptoms. Mononeuropathies,
      radiculopathies, motor palsies and acute painful neuropathies are more reversible
      forms of neuropathies. Their evolution is often unrelated to glycaemic control,
      vascular factors are more important in the pathogenesis and these complications
      are more common in middle aged and elderly men with type 2. diabetes mellitus.
      The diagnosis of neuropathies is based on following criteria: nerve conduction
      velocity studies; neurological examination; quantitative motor, sensory and
      autonomic function tests; neuropathic symptoms. Autonomic functions should be
      evaluated by standard cardiovascular reflex tests. Recently, reliable, however,
      simple and cheap methods such as the calibrated tuning fork and the monofilament
      are recommended to use for the diagnosis of sensory nerve dysfunction in everyday
      clinical practice.

PMID- 12073659
TI  - [The role of adrenal and gonadal hormones in the pathogenesis of autoimmune
      polyarthritis].
AB  - A growing body of recently published results suggest the role of adrenal
      androgens in the onset and development of chronic inflammatory process due to
      autoantigens. Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate
      (DHEA)--the major androgen products of the adrenal gland--have immunosuppressive
      effect inhibiting interleukin-6 production and substantially determining acute
      phase reaction. Decreased serum levels of DHEA and DHEAS has been observed in
      most of autoimmune diseases. Recent data suggest that adrenal hypoandrogenism
      comes from disturbed neuroendocrine, regulation due to hypothalamic effect of the
      inflammatory cytokines. On the other side, decreased adrenal androgen activity
      negatively influences the anabolic tonus of steroid hormone system while a
      relative enhancement of catabolic pressure occurs by the glucocorticoids.
      Moreover, the hypothalamus-hypophysis-gonadal axis can also be involved,
      resulting shifts in serum levels of prolactin, estrogens and gonadal androgens.
      All these hormonal changes can be summarised in decreasing the immunosuppressive
      tonus. This hypothesis connects the endocrine dysregulation with the development
      of autoimmune disorders. The new results promise not only a basically different
      theory of chronic inflammation but they will permit using new diagnostic tools as
      well as inducing substantially new and more effective therapeutic approaches.

PMID- 12073660
TI  - [Effects of piracetam on the cognitive functions verified by electrophysiologic
      methods].
AB  - The well-known psychoactive drug widely used in the daily clinical praxis, the
      piracetam has many therapeutical indications. The drug is extensively applied in
      the therapy of ischaemic stroke, aphasy as well as of dementias of several
      origins and age-depending cognitive disturbances. One of the most important
      effect of piracetam is the positive effect to the cognitive functions. In this
      publication the author reviews the most important studies, where significant
      effects of piracetam (chronic or single-dose treatment) were verified by means of
      electrophysiological methods. These studies proved objectively the positive
      psychoactive and cognitive effects of the drug, supporting the therapeutical
      indication of piracetam in such cases, where cognitive deficits are present.

PMID- 12073661
TI  - [Ultrasound screening program for neonates and infants in Hungary].
AB  - INTRODUCTION: A children's hospital in Budapest (The Madarasz Street Children's
      Hospital) and two children's department of two county hospitals (Toldy Ferenc
      Hospital, Cegled and Zala County Hospital, Zalaegerszeg) started a common
      ultrasound screening programme for children in 1990. OBJECTIVES: This three
      screening centres agreed which illnesses, pathological states and developmental
      disorders will be screened. In neonatological departments this screening was
      carried out usually in the first week of life. In the children's hospital, the
      majority of measurements was performed between 2 weeks and 3 months of the
      infants life time. The ratio between this two age group was 43.6 and 56.4%. The
      authors compared and analysed the results of screenings in neonates and those in
      infants. Another important objective of the programme was to compare the results
      of prae- and postnatal screening. METHODS: Examinations were carried out by up-to
      date instruments corresponding to the given period. Data for neonates were
      compared with those for infants and with clinical findings, analysed, stored in
      computers and yearly evaluated. Screenings were performed by neonatologists,
      pediatric radiologists or pediatricians with appropriate practice. RESULTS: The
      three centres examined altogether 51,688 children during their 10-years activity,
      and found 4758 pathological cases. The majority of pathological cases (3447) was
      renal and urinary tract disorders, in 1224 cases intracranial occurrences were
      diagnosed, whereas the remaining cases were mainly tumours or cysts in the liver,
      spleen or ovarium. CONCLUSION: Numerous pathological changes can be detected by
      ultrasound screening postnatally, which have great therapeutic significance and
      are very important for differential diagnostics. By comparing the results for
      neonates and infants, it can be established that screening in infancy is usually
      important if no screening was carried out in the neonate age, but control
      examinations should be performed as well, when it is justified by some
      physiological or pathological reason. In case of slight deviations, when the
      first examination cannot provide unambiguous diagnosis, later, repeated
      examinations can support an accurate diagnosis. Documentation of the results from
      neonate age and infancy facilitates the correct judgment in later pathological
      states.

PMID- 12073662
TI  - [Pathophysiology and therapeutic possibilities in twin-to-twin transfusion
      syndrome].
AB  - INTRODUCTION: Twin-to-twin transfusion syndrome is a threatening consequence of
      monochorionicity. Without therapeutic intervention it has approximately a 100%
      mortality rate, but due to therapeutic efforts it improved dramatically to about
      20-50% mortality. It is caused by arteriovenosus anastomoses within the placenta,
      that causes hormonal changes, polyhydramnios, hypertension of the recipient and
      weight discordance. AIMS: Detection of ultrasonographic and pathologic
      consequences of twin-to-twin transfusion syndrome. PATIENTS AND METHODS:
      Ultrasonographic and pathologic findings of six twin pairs were analysed with the
      common feature of twin-to-twin transfusion syndrome. RESULTS: Ultrasonographic
      and pathologic results were suggestive for fetal hypertension in all recipients
      and pulmonary stenosis in four of them. CONCLUSION: The prognosis of twin-to-twin
      transfusion syndrome can be improved significantly with serial amnioreduction,
      amniotic fenestration, laser ablation of connecting vessels or selective
      fetocidium. Proper therapy prevents the development of the serious clinical and
      pathological consequences of twin-to-twin transfusion syndrome.

PMID- 12073663
TI  - [Reform of the training of military surgeons in Hungary in the 1880's].

PMID- 12073664
TI  - Comparison of the risk of upper gastrointestinal bleeding associated with non
      steroidal anti-inflamatories.

PMID- 12073665
TI  - Ranitidine bismuth citrate in the treatment of Helicobacter pylori infection.
AB  - OBJECTIVE: Examine the effectiveness of treatments that include ranitidine
      bismuth citrate (RBC) for Helicobacter pylori infection. DESIGN: Prospective and
      randomised study. PATIENTS AND METHOD: 137 patients were included (62 women, 75
      males, average age 46.9 +/- 13) diagnosed with peptic ulcer and infection by
      Helicobacter pylori. None had received treatment previously. 67 patients were
      treated with RBC 400 mg bd and clarithromycin 500 mg bd for 14 days, and 70
      patients with RBC 400 mg bd, clarithromycin 500 mg bd and amoxycillin 1 g bd for
      7 days. The infection eradication was proven eight weeks after treatment end. The
      efficacy of treatment was evaluated using the intention-to-treat method. The
      Chisquare test (chi 2) was used for the statistical analysis of data. RESULTS:
      Infection in 48 out of 67 patients (71.64%) treated with RBC-clarithromycin for
      14 days was eradicated, versus 88.57% (62 out of 70) among those treated with RBC
      clarithromycin-amoxycillin for 7 days, with a significant difference between both
      regimens (p < 0.05). CONCLUSIONS: 7-day treatment with RBC-clarithromycin
      amoxycillin has a good eradication rate (88.57%) and represents a valid
      alternative to regimens including a PPI and two antibiotics, as both regimens
      have a similar efficacy. Results obtained with the double therapy of RBC
      clarithromycin for 14 days were not satisfactory, the rate of eradication being
      71.64%. The use of an RBC treatment for Helicobacter pylori infection should
      always be accompanied by two antibiotics in a triple therapy.

PMID- 12073666
TI  - Long-term outcome of patients with non-cardiac chest pain.
AB  - OBJECTIVE: To assess long-term outcome for patients with chest pain in our
      environment, to estimate direct resource use, and to evaluate the influence of
      patient views regarding pain origin on outcome. PATIENTS AND METHODS: All
      patients referred to our Department between 1994 and 1998 to undergo pH-metry as
      a result of chest pain were identified. Those detected were subjected to a
      structured direct interview on the telephone. RESULTS: 104 patients with a follow
      up period (since pH-metry) of 3.76 years were evaluated. Thirty nine percent of
      patients were free from pain (37.5%), and one had died from a seemingly unrelated
      cause (1%), whereas the rest still suffered from pain. The mean number of visits
      per patient during the last year was 2.83 to their general practitioner, 1.04 to
      an specialist, and 0.99 to an Emergency Unit; hospitalisations were 0.26, and ICU
      admissions 0.09. Patients who trusted medical diagnoses showed better outcomes
      than those who did not trust or understand them, in association with lower
      resource use, particularly Emergency Unit use. CONCLUSION: Patients with chest
      pain had a favourable life prognosis, but 60% still suffer from pain after nearly
      4 years of follow-up, which entails a relevant use of health-care resources.
      Trust in medical diagnosis seemingly influences outcome, and the use of
      diagnostic procedures to determine pain origin is thus likely beneficial for
      patient.

PMID- 12073667
TI  - Chronic hepatitis C in patients non responsive to antiviral therapy.

PMID- 12073668
TI  - [Spontaneous bacterial peritonitis caused by Haemophilus influenzae].

PMID- 12073669
TI  - [Nimesulide-induced hepatotoxicity].

PMID- 12073670
TI  - [Duodenal pseudolipomatosis].

PMID- 12073671
TI  - [Hemobilia caused by pericholedochal varices following cephalic
      duodenopancreatectomy].

PMID- 12073672
TI  - [Hepatic abscess caused by Streptococcus iintermedius as first manifestation of
      renal carcinoma].

PMID- 12073673
TI  - Comparative incidence of upper gastrointestinal bleeding associated with
      individual non-steroidal anti-inflammatory drugs.
AB  - OBJECTIVE: The existence of two isoforms of cyclo-oxygenase (COX), COX-1 and COX
      2, is now well established. Because inhibition of COX-1 by nonsteroidal anti
      inflammatory drugs (NSAIDs) is linked to gastrointestinal (GI) damage, agents
      with a better COX-2/COX-1 inhibition ratio may have less GI toxicity. The aim of
      this study was to compare the incidence of upper gastrointestinal bleeding (UGIB)
      in association with specific NSAIDs including the new "COX-2 preferential"
      inhibitors. PATIENTS Y METHOD: Individual incidence of NSAID-related UGIB in a
      health-authority area was estimated, based on cases of UGIB, sales of non-aspirin
      NSAIDs, and data of used doses in community subjects, during a four-year period.
      Comparisons were made by calculating individual rate-ratio (RR) and 95%
      confidence interval (CI) taking as a reference the specific NSAID with the lowest
      incidence of UGIB. RESULTS: The incidence of UGIB associated with thirteen
      specific NSAIDs included in the study varied greatly, from 1.7 per 1,000 person
      years for aceclofenac to 25.8 per 1,000 person-years for ketorolac. The use of
      "COX-1 preferential" inhibitors versus "COX-2 preferential" inhibitors was
      associated with a RR of 5.3 (95% CI, 2.78-10.04), and between NSAIDs with "COX-1
      COX-2 mixed" inhibition RR was 2.2 (95% CI, 1.13-4.28). CONCLUSIONS: Our results
      show that there are differences in GI toxicity according to specific NSAIDs. A
      substantial reduction in number of cases of UGIB could result from the use of
      NSAIDs with a "COX-2 preferential" inhibition.

PMID- 12073674
TI  - [Validation parameters of otoemissions with Echocheck].
AB  - GOALS: There are several papers that support the use of Echocheck system to
      exclude neonatal hypoacusis, but none of them compare it with the ILO systems,
      neither compare the internal parameters obtained versus those from a colour coded
      system. We are trying to demonstrate that both techniques are equivalent and
      valid. METHODS: Acoustic otoemissions were studied in four hundred and ninety
      four (494) newborn ears using Echocheck. They were classified as Normal, Not
      valid, No EOAEs and Invalid using a colour coded system. After this they were
      compared with the internal results registered by the system. On the other hand,
      otoemissions were obtained using both methods (Echocheck and ILO-88) in 135 ears
      and the results compared. RESULTS: The correlation between the results obtained
      through the colour coded system and those obtained from the internal register was
      absolute for those parameters previously determined. For the comparison between
      both systems, results did coincide in all cases except for two, in which there
      were only results with ILO and not with Echocheck. CONCLUSIONS: The validity of
      the test using this new system as well as the comparison of the results with
      those obtained from ILO systems has been demonstrated, therefore its use has been
      recommended for the early detection of hypoacusis in newborn due to the fact that
      it is simple to perform.

PMID- 12073675
TI  - [Unilateral polyposis: evaluation of preoperative tests].
AB  - The aim of this paper is to study a group of patients with occupancy of a nasal
      fossal, apparently by polyps, and being the other side of the nose normal.
      Evaluating on the one hand the true incidence of unspecific polyposis and, of
      other diagnosis, and on the other hand to compare the preoperative radiological
      findings with those seen during surgery. MATERIAL AND METHODS: A prospective
      study of 23 consecutive patients was carried out over a period of 30 months at
      the ENT Department of the Dr. Peset Hospital, in Valencia. A CT scan and
      preoperative biopsy was performed in all cases, the results of these being later
      compared with the surgical findings and the final histopathologic diagnosis.
      RESULTS AND CONCLUSIONS: A discrepancy between the preoperative biopsy and final
      diagnosis was found in 26% of the patients. The incidence of polyposis was 52%,
      inverted papilloma 26%, malignant tumours 13% and other diagnosis 8.6%. There is
      a good correlation between preoperative CT scans and surgical findings in those
      cases of polyposis and inverted papilloma, but not in those of malignant tumours
      as CT scans often underestimated these lesions.

PMID- 12073676
TI  - [Factors helping in the decision to change intubation for tracheotomy in critical
      patients].
AB  - We carry out a prospective study in order to determine the prognostic factors in
      the development of injuries of upper airways, and their influence in the decision
      to perform a tracheotomy. The time to tracheotomy was previously stated,
      according to the type of patient (neurological or non-neurological). This study
      includes the clinical data and the upper airways endoscopic exploration of 654
      patients with oro-tracheal intubation and mechanical ventilation for more than 48
      hours in a 6 year period. Three endoscopic explorations were carried out in the
      first month (early exploration), with two additional explorations at six and
      twelve months (late exploration). Using a multivariable statistical study we have
      analysed the prognostic factors and the risk groups for the development of later
      injuries of the upper airway of these patients. The later endoscopic exploration
      of the upper airways has shown injuries in 30 of 280 cases (11%). In this study,
      the main factor that determines the development of injuries of the upper airway
      was the time of intubation. The risk groups to develop later lesions of the upper
      airways include: patients with pathological background, patients with medical
      admissions, non-neurological patients and patients with serious lesions in the
      earlier endoscopic exploration. We conclude that it is necessary to state the
      time to perform a tracheotomy in patients with oro-tracheal intubation. It must
      be based on the own experience, the patient's clinical condition and the disease
      that caused hospital admission.

PMID- 12073677
TI  - [Globus Hystericus, personality and psychopathology].
AB  - The aim of this investigation is to establish if there is a relation between the
      Globus Hystericus (GH) and any psychopathological disorder. In order to do this
      we have evaluated, the psychological characteristics of a sample of patients that
      have attended the ENT clinic with G.H., and we have compared them with those of a
      control group from the same clinic, to see if there were differences between both
      groups, and if these were statistically significant. The results have show that
      there are significant differences in the personality of people with G.H. They
      present higher marks in the Neuroticism and Introversion variables from Eysenck's
      E.P.Q-A, besides presenting significant differences in the behaviour signs of
      depression, being evaluated these with the Beck Inventory B.D.I.

PMID- 12073678
TI  - [Design, maintenance, and exploitation of an oncologic database for patients with
      malignant tumors of the head and neck].
AB  - The oncological databases are essential in the evaluation of the results of
      patients with malignant tumours. We present the design of the database that
      collects the oncological information of patients with head and neck malignant
      tumours diagnosed in our centre since 1984, and the needs of maintenance and
      possibilities of exploitation.

PMID- 12073679
TI  - [Atypical Cogan syndrome. Clinical and laboratory spectrum. Report of 2 cases].
AB  - We show two atypical Cogan's syndrome cases in forty-seven and fifty-six years
      old individuals. Characteristical symptoms of the syndrome were detected in both
      (interstitial keratitis, sensorineural deafness and vestibular dysfunction), but
      they could be considered as unusual because of the association of systematic
      symptoms and an onset with hearing loss. In both cases there was an increase in
      erythrosedimentation rate and immunoglobulins levels, as well as high titles for
      rheumatoid factor and non-specific autoantibodies. By means of a Western-blot
      technique, several chochlear antibodies with distinct molecular weight were
      detected, but the 68 KD appeared in both. Metil-prednisolone treatment did not
      avoid ocular and auditive reactivation in ne of the patients.

PMID- 12073680
TI  - [Monostotic fibrous dysplasia of the frontal sinus with orbital extension].
AB  - We present the case of a localized monostotic fibrous dysplasia in the frontal
      sinus with orbital extension and persistency after the first surgery; it had to
      be operated again with a fronto-orbitary reconstruction. The fibrous dysplasia is
      a rare bony alteration with transformation of the healthy bony tissue for a
      disestructuredone. Its etiology is unknown and can be associated to different
      syndromes, such as Albright's Disease. Its treatment is surgical, but presents a
      high percentage of recurrence, this is the xenson why it needs a close follow up.

PMID- 12073681
TI  - [Report of a case: large tonsillolith in palatine tonsil].
AB  - A 69-year-old woman presented with a one-year history of dysphagia and a hard
      overgrowth of the right palatine tonsil visible in oral examination. Computerized
      Tomography scan showed a big calcified lesion inside the tonsil not seen in a
      pharyngoscopy. Tonsillectomy was performed and a giant tonsillolith was found
      inside the resected piece. The calculus was 3 x 2 x 2.3 cm and with an irregular
      pyramidal shape. Normal tonsillar tissue with many colonies of Actionomyces
      inside the tonsillar crypts was the definitive pathological feature.

PMID- 12073682
TI  - [Primary intraoral epithelioid hemangioendothelioma. Case report and review of
      the literature].
AB  - Epithelioid Hemangioendothelioma (EH) is a vascular neoplasm of soft tissue,
      recently described by Weiss and Enzinger. The biologic al behavior of the tumor
      has a intermediate malignant potential, in the sense that it has an indolent
      course, with the potential for recurrence, but rarely metastasizes. This tumor
      arises from medium- to large-sized vessels, primarily involves the soft tissues
      of the extremities, as well as the liver, lung, and bone, and rarely occurs in
      the head and neck region. Only fifteen well--documented cases of Epithelioid
      Hemangioendothelioma involving the head and neck region have been reported. Nine
      cases have been recently reported in the oral cavity. This is a report of one
      additional case in the tongue. Because of the intermediate malignant potential of
      Epithelioid Hemangioendothelioma, complete tumor resection is recommended for
      intraoral lesions.

PMID- 12073683
TI  - [Neurosensory sudden deafness, blood hyperviscosity syndrome, and diabetes
      mellitus].
AB  - Diabetes mellitus is considered a risk factor for sensorineural sudden deafness.
      Its pathogenesis remains unknown. However, the physiopathological implication of
      a hyperviscosity syndrome in diabetics and patients bearing of sudden deafness
      can mean the nexus between the two entities. Total blood viscosity and
      erythrocyte adhesion were haemorheological parameters significatively higher in
      blood of diabetics with sudden deafness than in normal hearing controls.
      Moreover, erythrocyte filterability and deformability were lower in diabetics,
      but it was not statistically significative. These findings help to guide therapy
      in these patients towards specific measures to improve blood viscoelastic
      properties.

PMID- 12073684
TI  - Reducing the hospital workforce: what is the role of human resource management
      practices?

PMID- 12073686
TI  - Strengthening the system: Joint Commission standards and building on what we
      know.

PMID- 12073685
TI  - A struggle with obligation: ethical reflections on a transplantation program.

PMID- 12073687
TI  - Cultural, ethnic, and religious diversity in service delivery.

PMID- 12073688
TI  - Patterns of health and illness: the effects of poverty on health.

PMID- 12073690
TI  - Overcrowding and fiscal pressures in emergency medicine.
AB  - Emergency departments in America are disappearing at an alarming rate. Those that
      remain face a daily ordeal of overcrowding and budgetary shortfalls. The reasons
      for this phenomenon include changes in reimbursement rates by managed care
      organizations, the nationwide reduction of hospital beds, the nursing shortage, a
      more acute patient mix, and a general deterioration of the healthcare safety net.
      Another reason--more vital today than ever before--is the uncompensated
      integration of EDs into governmental disaster planning and response. Despite
      their importance to society, the emergency department is the first to be cut.
      Emergency departments are much more than the nation's last line of defense for
      the medically indigent; they are the frontline caregivers to all of us, providing
      care during our most vulnerable times: emergencies and disasters.

PMID- 12073689
TI  - Hospital Topics--80 years in the health services field.

PMID- 12073691
TI  - Agencies start TalkingQuality, give hospitals tools to educate public.
AB  - New government web site designed to help health systems and hospitals provide
      consumers with quality report cards and other information regarding health care
      quality measurement.

PMID- 12073692
TI  - QI focus leads to IT solutions systemwide.
AB  - Technology wasn't the starting point, but new system provides ample information
      for positive change in Indianapolis.

PMID- 12073693
TI  - The patient is the winner in the pursuit of perfection.
AB  - With $2 million in grant money, seven facilities aim to improve patient care,
      safety, and disease states.

PMID- 12073694
TI  - Removing patient irritants improves care.
AB  - Getting rid of those irritating little problems, a team provides the catalyst for
      patient satisfaction improvements.

PMID- 12073695
TI  - Statins for all?

PMID- 12073696
TI  - Key developments in cardiovascular medicine.

PMID- 12073697
TI  - Casebook: chest pain.

PMID- 12073698
TI  - Managing the patient with claudication.

PMID- 12073699
TI  - Current thinking in the treatment of hypertension.

PMID- 12073700
TI  - Cardiomyopathy in practice.

PMID- 12073701
TI  - The recognition and treatment of pericarditis.

PMID- 12073702
TI  - Current management of heart failure.

PMID- 12073703
TI  - Measuring pulmonary function in practice.

PMID- 12073704
TI  - Managing the patient with polycystic kidney disease.

PMID- 12073705
TI  - Migraine in women.

PMID- 12073706
TI  - Professional development plans: an introduction.

PMID- 12073708
TI  - Metastatic prostate cancer.

PMID- 12073709
TI  - Prostatic carcinoma with emphasis on Gleason's Grading: an institution based
      experience.
AB  - OBJECTIVE: To grade prostatic carcinomas according to the Gleason's Grading
      System and see whether the frequency of incidental carcinoma is significant.
      METHOD: Retrospective study of all consecutive cases of prostatic adenocarcinoma
      diagnosed at Aga Khan University Hospital (AKUH) between January 1st, 1996 and
      December 31st, 1999. SETTING: The histopathology section of AKUH, Karachi.
      OBSERVATION: Prostatic adenocarcinomas comprised 14.2% of all prostate specimens.
      There were 3 types of specimens i.e. transurethral resection, suprapubic
      prostatectomies and core biopsies. The mean age was 72.1 years; 68.1% patients
      were 65 years or older. The majority of the tumours were moderately
      differentiated (Gleason's scores 5,6 or 7). Grading was not possible in most core
      biopsies. The frequency of incidental carcinoma was 31.4%. CONCLUSION: Majority
      of tumours were moderate to poorly differentiated, indicating that prostatic
      adenocarcinoma is an aggressive disease. The frequency of incidental carcinoma
      was also high emphasizing need for more aggressive prostatic evaluation in the
      vulnerable age group.

PMID- 12073710
TI  - Spectrum of chronic liver disease in a tertiary care hospital.
AB  - OBJECTIVE: To ascertain the nature and etiology of the chronic liver disease
      occurring in the northern part of Pakistan. METHODS: Results of the liver
      biopsies performed at Shifa International Hospital from 1994-2000 were reviewed.
      The reason for the biopsy and results were noted and analyzed. RESULTS: A total
      of 518 liver biopsies were performed during this period. Most patients were
      between the ages of 31-50 years (range 10-70 years). Males and females were
      equal. Three hundred fifty four (68.3%) patients had chronic hepatitis. Of these
      86% had hepatitis C, 10.7% hepatitis B and 3.1% both B and C. Of 41 (7.9%)
      hepatocellular carcinomas, 29.3% were due to hepatitis C and 14% due to hepatitis
      B virus infection. Etiology was not known in 53% cases of HCC. Other categories
      included chronic hepatitis with early cirrhosis (4.8%), cirrhosis (3.1%),
      adenocarcinoma (4.6%) and other miscellaneous conditions. CONCLUSION: Chronic
      hepatitis C makes the largest percentage in this series of cases followed by
      hepatocellular carcinoma, cirrhosis and metastatic adenocarcinoma as causes of
      chronic liver disease in this part of Pakistan.

PMID- 12073711
TI  - Neonatal thyroid screening--the Shifa experience.
AB  - OBJECTIVE: To evaluate the results of T4, TSH analysis and pattern of
      presentation in babies born at our hospital. METHOD: We retrospectively reviewed
      the data collected from T4, TSH screening on all babies delivered at our
      Hospital, where the blood was drawn within the first 4 days of life. Period under
      evaluation was from October 1995 to October 1998. Shifa Reference values were
      used. RESULTS: Blood sample were collected from 997 babies within 4 days of
      birth. Nine hundred and forty nine (95.2%) were evaluated after 24 hours. and
      48(4.8%) in less than 24 hours of age. A high TSH was reported on 166 (16.8%)
      babies and a low T4 was reported on 78 (7.9%) babies. Statistical analysis showed
      a similar sensitivity for T4 and TSH (100%) but a higher specificity for T4
      (93.1%) as compared to TSH (86%). A high-TSH with a low T4 was reported in 5
      (0.5%) babies out of which 1 case was confirmed as congenital hypothyroidism
      requiring permanent thyroxin replacement and one case manifested a picture
      consistent with transient hypothyroidism. A low TSH with a low T4 was seen in 2
      cases, however, they were all premature babies on antibiotics. CONCLUSION:
      Congenital hypothyroidism may be more frequent in our population and for the
      purpose of screening babies T4 values would carry a higher positive predictive
      value than TSH. Combining T4 TSH assays would however reduce the call back rate
      quite significantly but may prove to be a bit more expensive.

PMID- 12073712
TI  - Lumbar disc prolapse: management and outcome analysis of 96 surgically treated
      patients.
AB  - OBJECTIVE: To evaluate the presentation, diagnosis and management outcome of
      surgically treated patients of lumbar disc prolapse. DESIGN: This is a
      prospective study. SETTING AND DURATION OF STUDY: The study was conducted at
      Department of Neurosurgery, Chandka Medical College Hospital, Larkana over a
      period of three years. SUBJECT AND METHODS: Patients were selected using
      following neuroimagings like plain radiographs, myelograms, CT myelograms and MRI
      Scan of lumbosacral spine. The operative procedure applied was hemilaminectomy
      and removal of herniated disc material. Postoperatively patients were analyzed
      for outcome by standard subjective analysis (Mac nab criteria), objective
      examinations and radiographic studies. RESULTS: There were 96 patients, 70 males
      and 26 females. Predominant mode of presentation was low back pain with radiation
      to leg (46.9%), neurogenic claudication in 18 patients (18.7%). Eighty Six
      percent of the disc prolapses were found at L4 L5 and L5 SI levels. Complication
      rate was 14.6% with infections being commonest. Excellent to good outcome was
      found in 85.4% of the cases. Mean follow up period was 18 months. CONCLUSION:
      Surgery for cauda equina syndrome and motor deficits has a good outcome with
      hemilaminectomy and is the best surgical option for large disc prolapses.

PMID- 12073713
TI  - Haemodynamic effects of unilateral spinal anesthesia in high risk patients.
AB  - OBJECTIVE: To assess whether a unilateral spinal anaesthesia using 0.5%
      hyperbaric Bupivacaine will restrict the sympathetic block to avoid the undesired
      cardio vascular effects. METHODOLOGY: In this study 40 ASA III and IV patients
      aged between 60-90 years undergoing unilateral lower limb surgery were included.
      All patients received unilateral spinal anaesthesia using hyperbaric 0.5%
      Bupivacaine (1.1-1.8 ml according to patient's height). Patients were placed in
      the lateral position with operated side down and kept in this position for 10
      minutes. Motor and sensory levels were assessed, and haemodynamic alterations
      were monitored for 30 minutes after initiation of spinal anaesthesia. RESULTS:
      Unilateral spinal anaesthesia is very effective in restricting the sympathetic
      block as all high risk patients showed minimal haemodynamic changes following the
      technique. CONCLUSION: Unilateral spinal anaesthesia is effective in restricting
      the sympathetic block in high risk patients.

PMID- 12073714
TI  - Interventions for control of road traffic injuries: review of effectiveness
      literature.
AB  - OBJECTIVE: In 1998, road traffic injuries were estimated to be the 9th leading
      cause of loss of healthy life globally and are projected to become the 3rd
      leading cause by 2020. The majority of this burden can be located in the
      developing world where most of the projected increase will occur. Yet health
      systems are least prepared to meet this challenge in these countries. At the same
      time, there are effective interventions for road traffic injuries being
      implemented in the developed world. An extensive review of the literature reveals
      more than 16 different interventions in four categories that have been
      implemented. Renewed testing of these and new interventions will take both time
      and funds--resources that are scarce in developing countries. As a result, it is
      imperative to study the effectiveness of those interventions already tested and
      attempt to evaluate their potential implementation in developing countries.
      METHOD: Literature review to identify effective interventions and the magnitude
      of the effects. RESULTS: Four broad classes of interventions can be identified
      from the literature; health education/awareness, legislation, product design and
      environmental modifications. CONCLUSION: The issues for the developing countries
      are affordable, infrastructure and sociocultural in implementation of these
      strategies. The road traffic injuries are also underreported and hence under
      represented at the priority setting stage. Road safety should be high on the
      agenda as it can save a lot of lives and disability. Public health professionals
      should assess and advocate road safety in developing countries.

PMID- 12073715
TI  - Prevalence of hearing impairment in siblings of deaf children.
AB  - OBJECTIVE: To assess the prevalence of hearing impairment in siblings of children
      with profound to total hearing impairment. METHOD: Two hundred and twenty
      siblings of children at a deaf school in Karachi completed the screening program.
      This consisted of a questionnaire and pure tone audiometry. RESULTS: One out of
      three (73 siblings) had a threshold of 25 dB or greater in their better ear. In a
      population, already aware of hearing loss, we note that only fifteen siblings had
      a previous audiogram. Although a positive family history is associated with
      hearing impairment in the siblings, no increase due to consanguineous marriages
      was noted. CONCLUSION: This assessment has underlined the need to increase public
      awareness of hearing impairment. It has also exposed the lack of it in families
      exposed to the condition.

PMID- 12073716
TI  - Abnormalities of conduction after total correction of Fallot's tetralogy: a
      prospective study.
AB  - OBJECTIVE: To determine the frequency of post-operative conduction abnormalities
      in Pakistani patients undergoing total correction for Fallot's Tetralogy.
      PATIENTS AND METHODS: One hundred and fifteen patients of Fallot's Tetralogy
      underwent definitive repair between January, 1999 and April, 2000. Their mean age
      was 12.89 years (range 3-30 years). One hundred nine patients (94.78%) had severe
      cyanosis and 6 patients (5.21%) were moderately cyanotic due to mild right
      ventricular outflow tract (RVOT) obstruction. Thirty percent patients required
      frequent hospital admissions within 6 months before the time of operation due to 
      hyper-cyanotic spells. The mean haematocrit was 50.83 (range 28-71). The majority
      of patients were in NYHA class-III (57%) and 45% had previous palliative shunt
      procedures done. Surgical access was through the RVOT in 90% cases and trans
      atrial in 10%. RVOT patch was used in 55.9%, Pulmonary artery patch in 13.5% and
      trans-annular patch in 17.1% of cases. RESULTS: The mean bypass time was 79.15
      min and the mean cross clamp time 51.23 min. Average stay in the intensive care
      unit was 4.48 days. Twenty-three patients required re-exploration for bleeding.
      Sixty-nine patients required inotropic support. Fifteen patients had transient
      heart blocks and two had complete heart block requiring permanent pace-maker.
      Nineteen patients had various transient arrhythmias which were managed medically.
      Univariate analysis showed that higher age at operation, low preoperative heart
      rate, prolonged bypass time, prolonged cross clamp time and presence of patch on
      pulmonary artery were more common in patients who developed various heart blocks.
      However, none of these factors had statistical significance or definitive cause
      effect relationship with heart blocks. CONCLUSION: With careful surgical
      technique, total correction of Fallot's tetralogy can be conducted in children
      and young adults, with a very low risk of conduction abnormalities.

PMID- 12073717
TI  - Giant Askin tumor: a diagnosis and therapeutic challenge.

PMID- 12073718
TI  - View box case--2. Mid-colic intussusception.

PMID- 12073719
TI  - Determination of anti-microbial susceptibilities of Haemophilus influenzae,
      Streptococcus pneumoniae and Moraxella catarrhalis.
AB  - OBJECTIVE: A retrospective study to determine the antibiotic resistance pattern
      seen in respiratory tract pathogens. MATERIALS AND METHODS: All sputum samples
      received during one year period (2000) were cultured by standard laboratory
      technique and antibiotic sensitivity was performed by Kirby Bauer disc method.
      RESULT: A total of 238 respiratory pathogens were isolated. All three isolates
      (Haemophilus influenzae, Streptococcus pnuemoniae and Moraxella catarrhalis) were
      highly resistant against Trimethoprim Sulfamethoxazole. Strep. pnuemoniae was not
      resistant to Penicillin. Rest of the antibiotics showed good response.
      CONCLUSION: Strep. pnuemoniae is still very sensitive to Penicillin and all three
      pathogens were resistant to Timethoprim Sulfamethoxazale.

PMID- 12073720
TI  - Antibiotics.

PMID- 12073721
TI  - Gaining adequate interdental space with modified elastic separating rings:
      rationale and technique.
AB  - Restoring a tooth with an inadequate contact point and root proximity is a
      challenge to the practitioner. Ignoring such situations or making compromises in
      the treatment plan may hinder a successful treatment outcome. Treatment options
      include strategic extractions, sectional orthodontics, and minor orthodontic
      movements. The purpose of this article is to discuss the clinical problems and
      difficulties arising from this situation and to present a modified treatment
      modality through two case reports. Elastic separating rings, which open an
      interdental space for placing orthodontic appliances, can be modified to serve as
      a preprosthetic means for solving mesiodistal crowding of teeth in daily
      practice. The classic method is modified by the use of elastic rings in
      sequentially increased thickness, so that the space gained with one ring is
      followed and increased with a thicker one. An orthodontic background and special
      instruments are not necessary.

PMID- 12073722
TI  - Long-term clinical success of all-ceramic posterior restorations.
AB  - Modern all-ceramic systems offer a highly esthetic, biocompatible, and functional
      alternative to traditional restorative materials. Such systems allow for a wide
      range of indications, from inlays to multiple-unit fixed partial dentures, and
      are increasingly used in posterior regions of the mouth. Many of these systems
      have been introduced to the market only recently. However, new materials and
      techniques should be followed up and their clinical performance proven for at
      least 5 years before they become routine modalities of treatment. This article
      reviews the current literature and scientific data on the long-term success of
      all-ceramic restorations in the posterior region and compares and discusses
      alternative treatment options.

PMID- 12073724
TI  - The vertical heights of maxillary and mandibular bones in panoramic radiographs
      of dentate and edentulous subjects.
AB  - OBJECTIVE: The purposes of this study were to determine the variation in
      maxillary and mandibular vertical measurements made from panoramic radiographs
      and to assess differences in measurements between dentate and edentulous jaws.
      METHOD AND MATERIALS: A total of 192 alveolar ridges (96 dentate and 96
      edentulous) were examined. The mean ages of the dentate and edentulous groups
      were 51.05 and 59.98 years, respectively. Measurements were made from reference
      lines drawn from anatomic landmarks on standardized panoramic radiographs.
      RESULTS: In the dentate group, there was no statistically significant difference
      between men and women in the height of the maxilla. However, the height of the
      mandible was significantly greater in men than in women. In the edentulous group,
      the heights of the maxilla at the anterior and first premolar regions were
      significantly greater in men than in women. In the same group, mandibular heights
      were also significantly greater in men than in women. Reductions in the height of
      the edentulous mandible and maxilla were significantly more pronounced in women
      than in men. The decrease in the vertical height of the maxilla was not
      statistically significant in men. CONCLUSION: There are differences between the
      sexes in alveolar ridge resorption after tooth loss.

PMID- 12073723
TI  - The atraumatic restorative treatment (ART) approach for the management of dental
      caries.
AB  - There is worldwide interest in and increasing usage of the conservative
      atraumatic restorative treatment technique or approach for the restoration of
      primary and permanent teeth. However, most published data on the clinical
      performance of the newer, high-strength esthetic conventional glass-ionomer
      restorative cements marketed for the procedure have been derived from short-term
      studies. There have been very few reports comparing different types of
      restorative materials and methods of cavity preparation. In primary teeth, after
      1 year, success rates have been approximately 80% to 95% for Class I and Class V
      single-surface restorations, 55% to 75% for Class II multisurface restorations,
      and 35% to 55% for Class III and Class IV restorations. In permanent teeth, after
      2 to 3 years, success rates have been approximately 90% for Class I and Class V
      single-surface restorations, but little data have been reported for other
      restoration classes. Failures usually result from restoration losses, fractures,
      and wear. Further improvements in the design of hand instruments and in the
      mechanical properties of the newer glass-ionomer cements are required. Currently,
      use of the atraumatic restorative treatment approach should be restricted to
      restoration of single-surface caries lesions, especially in permanent teeth, and
      to sealing of occlusal fissures in selected teeth.

PMID- 12073725
TI  - Opalescence of dental porcelain enamels.
AB  - OBJECTIVE: The objective of this study was to compare the microstructures of
      teeth, natural opals, and opal dental enamel porcelains to examine the mechanisms
      that cause opalescence. METHOD AND MATERIALS: Four dental porcelains, a natural
      opal mineral, and a human tooth were examined. Replicas were assessed in
      transmission electron microscopy for features that would cause opalescence.
      Enamel dental porcelains denoted as "light" were selected for the study. X-ray
      diffraction and color analyses of the porcelains were also performed. RESULTS:
      All the materials were opalescent, to varying degrees. The porcelains with fewer
      microscopic features were less opalescent. The presence of dispersed particles or
      a phase-separated glass was found to cause opalescence in dental porcelains.
      CONCLUSION: A phase-separated glass in one enamel porcelain best resembled the
      microstructure of natural opal mineral and teeth, and this was the most
      "opalescent" material.

PMID- 12073726
TI  - Assessing microleakage in resin composite restorations rebonded with a surface
      sealant and three low-viscosity resin systems.
AB  - OBJECTIVES: The aim of this study was to assess the ability of three low
      viscosity resin systems (Unibond, Single Bond, and Fluorseal), used as rebonding
      agents, and a specific surface-penetrating sealant (Fortify) to prevent
      microleakage in Class V resin composite restorations. METHOD AND MATERIALS: Fifty
      Class V cavities with the occlusal margin in enamel and the cervical margin in
      dentin and cementum were prepared on both the buccal and lingual surfaces of
      sound extracted premolars and restored with a hybrid light-cured resin composite.
      After finishing and polishing, restorations were randomly assigned to one of five
      equal groups (n = 10): a control, without surface sealing, and four experimental
      groups in which margins were etched and rebonded. Specimens were thermocycled,
      immersed in a 50% silver nitrate solution, sectioned longitudinally, and analyzed
      for leakage at the occlusal and cervical interfaces. RESULTS: Statistical
      analysis showed significantly less leakage at the enamel margins for all groups.
      Fortify and Unibond were statistically similar and provided better marginal
      sealing at dentin and cementum interfaces. Fluorseal showed the poorest ability
      to prevent microleakage. CONCLUSION: The rebonding technique may substantially
      minimize microleakage at dentin and cementum margins of composite restorations,
      when a resin system with sufficiently low viscosity is used as a surface sealant,
      regardless of whether it has been specified for such a purpose.

PMID- 12073727
TI  - Effect of glass fiber reinforcement on the flexural strength of different denture
      base resins.
AB  - OBJECTIVE: Different types of fibers have been added to polymer materials to
      improve their mechanical properties. Glass fibers have been used in either
      continuous or woven form as a strengthening material. The aim of this study was
      to investigate the effect of a new glass fiber reinforcement system on the
      flexural strength of three different denture base resins (heat polymerized,
      autopolymerized, and photopolymerized). METHOD AND MATERIALS: Ninety specimens
      were formed in a specially designed mold to produce identical specimens in
      accordance with each manufacturer's recommendations. RESULTS: The fibers of Stick
      and Stick Net were well impregnated with the resin of polymer matrix. Stick and
      Stick Net reinforcement significantly enhanced the flexural strength of the
      tested specimens. In all groups, specimens reinforced with Stick glass fibers
      exhibited the highest flexural strength, followed by Stick Net glass fibers. The
      control group specimens without fiber exhibited the lowest values. CONCLUSION:
      The process of reinforcement of denture base resins with glass fiber may be a
      useful means of strengthening denture bases beyond their normal limits.

PMID- 12073729
TI  - Subcutaneous emphysema.

PMID- 12073728
TI  - Clinical evaluation of audiometric control root canal treatment: a retrospective
      case study.
AB  - OBJECTIVE: The purpose of this study was to retrospectively assess the success of
      endodontic treatment that had been guided by audiometric (electronic)
      measurement. METHOD AND MATERIALS: The lengths of 66 infected root canals that
      demonstrated periapical pathosis were accurately measured by the Sono-Explorer
      before root canal obturation. The results over time intervals of 1 month to 20
      years were evaluated on the basis of radiographic examinations. RESULTS: The rate
      of successful treatment was 90.4% for short-filled root canals, 94.5% for flush
      filled root canals, and a low 50.0% for long-filled root canals. The rate of
      successful endodontic therapy was 87.8% for restorations that did not exceed the
      apical foramen but reached the apical constriction and 95.3% if cases in which
      the apical radiolucencies were disappearing were included as successes. If cases
      of unintentional long-filling (overextension) were excluded, the success rate was
      as high as 98.4%. CONCLUSION: The poor performance of overfilled root canals
      indicates that practitioners should not overextend these restorations. Use of the
      Sono-Explorer aided successful treatment of infected root canals.

PMID- 12073730
TI  - Enzooticity of the dogs, the reservoir host of Thelazia callipaeda, in Korea.
AB  - The reservoir hosts of Thelazia callipaeda were examined. The eyes of the 76 dogs
      raised at farm. 78 military dogs (shepherds), 96 cattle, and 105 pigs were
      investigated for the presence of eyeworm. Among them, six worms of T. callipaeda
      were collected from two dogs raised at farm (2.7%), and 188 worms from 26
      shepherds (33.5%). No worms were recovered from the cattle or pigs. These results
      suggest that the dogs, especially the military dogs are serving as a reservoir
      host of T. callipaeda in Korea.

PMID- 12073731
TI  - Tegumental ultrastructures of Echinoparyphium recurvatum according to
      developmental stages.
AB  - The present study was performed to observe tegumental ultrastructure of
      Echinoparyphium recurvatum according to developmental stages. Worms (1, 3, 5 and
      15-day old) were recovered from chicks experimentally infected with metacercariae
      from Radix auricularia coreana. One-day old worms were elongated and ventrally
      concave, and covered with peg-like tegumental spines except the adjacent areas of
      the head crown and excretory pore. Type I sensory papillae were distributed on
      the lip of the oral sucker, and grouped ciliated papillae were around the oral
      sucker. Peg-like tegumental spines were densely distributed on the anterior
      surface of the ventral sucker level. The ventral sucker had an aspinous tegument
      and no sensory papillae. Tegumental spines on the posterior surface of the
      ventral sucker level were sparsely distributed and disappeared posteriorly. In 3
      and 5-day old worms, the tegument around the oral sucker was aspinose and
      wrinkled concentrically. The ventral sucker had a wrinkled tegument and many
      bulbous papillae. Type I sensory papillae were distributed between the bulbous
      papillae. Tegumental spines were spade-shaped with a terminal tip. A total of 45
      collar spines including 4 end group ones on both ventral corners was alternately
      arranged in 2 rows. The 15-day old worms were very stout and their tegumental
      spines were tongue-shaped without a terminal tip. From the above results, it is
      confirmed that the surface ultrastructure of E. recurvatum was generally similar
      to that of other echinostomatid flukes. However, some features, i.e.,
      morphological change of tegumental spines and appearance of sensory papillae on
      the ventral sucker according to development, and number, shape and arrangement of
      collar spines, were characteristic, which may be of taxonomic and bioecological
      significance.

PMID- 12073732
TI  - Detection of vivax malaria sporozoites naturally infected in Anopheline
      mosquitoes from endemic areas of northern parts of Gyeonggi-do (Province) in
      Korea.
AB  - We investigated population densities of mosquitoes infected with sporozoites in
      three highly epidemic areas of Josan-ri and Jangpa-ri (Paju City) and Dongjung-ri
      (Yeoncheon County) in Korea. Anopheline mosquitoes were collected from both
      indoors and outdoors by human baiting collection method during the period of the
      first week of June to the second week of September 1999. Total 13,296 female
      mosquitoes were collected and 8,650 (65.1%) were Anophelines. Thirty seven
      percent (3,199) of the Anopheline mosquitoes were captured outdoors and 63.9%
      (5,531) indoors. Employing a sandwich enzyme-linked immunosorbent assay (ELISA),
      we analyzed a total of 7,820 Anopheline mosquitoes and found that 7 Anopheline
      mosquitoes were infected with sporozoites. The positive rate in Josan-ri was
      0.14% (5/3,500) and 0.15% (2/1,370) in Jangpa-ri. The total positive rate in all
      three surveyed areas was 0.09% (7/7,820). The mosquitoes infected with the
      sporozoites were detected on June 28th (n = 2), July 5th (n = 1), July 19th (n =
      1), August 9th (n = 1), September 6th (n = 1), and the last one on September 13th
      (n = 1). They were all classified as Anopheles sinensis, which showed positive
      reaction in ELISA test. Therefore it might be concluded that Anopheles sinensis
      plays an important role in re-emerging malaria transmission in Korea.

PMID- 12073733
TI  - Characterization of partially purified 8 kDa antigenic protein of Clonorchis
      sinensis.
AB  - The 8 kDa antigenic protein of Clonorchis sinensis was partially purified by
      ammonium sulfate precipitation and subsequently by a column chromatographic
      steps. The purified protein was separated into 7 and 8 kDa protein bands through
      SDS-tricine gel electrophoresis, while the protein was found to migrate to a 8
      kDa band in 7.5-15% SDS-PAGE. The molecular weight of the antigen was estimated
      to be 110 kDa by Superose 6 HR 10/30 gel filtration. The purified antigen
      strongly reacted with the human sera of clonorchiasis. The hyperimmune sera of
      BALB/c mice immunized against the 8 kDa protein were reacted with both the crude
      extract and the excretory-secretory product of adult worms, but not with the
      metacercarial extract. Immunohistochemical staining demonstrated that the protein
      was distributed to the tegument and subtegumental cells and also to the seminal
      receptacle. The present findings suggest that the 8 kDa protein is a partition of
      the multicomplex protein originating from various organs of adult C. sinensis,
      and that it is composed of several 7 and 8 kDa proteins.

PMID- 12073734
TI  - Excretory bladder: the source of cysteine proteases in Paragonimus westermani
      metacercariae.
AB  - The cysteine proteases of Paragonimus westermani metacercariae are involved in
      metacercarial excystment, host immune modulation, and possibly in tissue
      penetration. In order to clarify the origin of the enzymes, 28 and 27 kDa
      cysteine proteases in metacercarial excretory-secretory products were purified
      through the FPLC system using Mono Q column chromatography. The polyclonal
      antibodies to the enzymes were produced in BALB/c mice. Immunolocalization
      studies revealed that both cysteine proteases were distributed at the linings of
      excretory bladder and excretory concretions of the metacercariae. It was
      suggested that the excretory epithelium of P. westermani undertake the secretory
      function of metacercarial cysteine proteases, in addition to its role as a route
      for eliminating waste products.

PMID- 12073736
TI  - A pediatrician's view. On joints and stuff.

PMID- 12073735
TI  - Degradation of immunoglobulins, protease inhibitors and interleukin-1 by a
      secretory proteinase of Acanthamoeba castellanii.
AB  - The effect of a secretory proteinase from the pathogenic amoebae Acanthamoeba
      castellanii on host's defense-oriented or regulatory proteins such as
      immunoglobulins, interleukin-1, and protease inhibitors was investigated. The
      enzyme was found to degrade secretory immunoglobulin A (sIgA), IgG, and IgM. It
      also degraded interleukin-1 alpha (IL-1 alpha) and IL-1 beta. Its activity was
      not inhibited by endogenous protease inhibitors, such as alpha 2-macroglobulin,
      alpha 1-trypsin inhibitor, and alpha 2-antiplasmin. Furthermore, the enzyme
      rapidly degraded those endogenous protease inhibitors as well. The degradation of
      host's defense-oriented or regulatory proteins by the Acanthamoeba proteinase
      suggested that the enzyme might be an important virulence factor in the
      pathogenesis of Acanthamoeba infection.

PMID- 12073737
TI  - A child with a fever of unknown origin.

PMID- 12073738
TI  - Pediatric rheumatology.

PMID- 12073739
TI  - Malignant bone tumors presenting as musculoskeletal pain.

PMID- 12073740
TI  - Laboratory evaluation of children with rheumatic disease.

PMID- 12073741
TI  - Assessing and enhancing adherence to medical regimens for juvenile rheumatoid
      arthritis.

PMID- 12073742
TI  - Resident's column: pediatric rheumatology.

PMID- 12073743
TI  - The role of epidemiology in graduate medical education.

PMID- 12073744
TI  - The role of NCI-designated cancer centers in the nation's fight against cancer.

PMID- 12073745
TI  - Oncologists' knowledge, attitudes and practices related to cancer treatment
      clinical trials.
AB  - Native Hawaiians have high incidence rates of cancers diagnosed in late stages
      and, thus, many might benefit from participation in cancer clinical trials. A
      survey was developed to explore knowledge, attitudes, and practices of Hawai'i
      oncologists with regard to cancer treatment clinical trials and Native Hawaiian
      participation in them. Findings suggest that most cancer specialists are
      supportive of clinical trials. However, physicians identified a number of
      barriers to Native Hawaiian participation in clinical trials. Ways to increase
      participation in clinical trials are suggested.

PMID- 12073746
TI  - Laparoscopic donor nephrectomy in Hawaii.
AB  - Laparoscopic donor nephrectomy for transplant is a minimally invasive, effective,
      and safe operation that also provides less post-operative pain and earlier return
      to pre-donation activity. In review of the first 10 cases, no major complications
      occurred and mean hospital stay was 3.7 days. All recipients of these kidneys
      displayed excellent allograft function (mean creatinine--1.5 mg/dL) and no
      ureteral problems. Successful use of this procedure has also resulted in a steady
      increase in the number of living transplants performed in Hawaii and perhaps this
      will impact the 330 patients currently awaiting renal transplant.

PMID- 12073747
TI  - Parental permission for children's independent outdoor activities. Implications
      for injury prevention.
AB  - BACKGROUND: Parental supervision is an important factor related to childhood
      injuries. However, little research has been done on; what outdoor activities
      children believe they are allowed or their parents allow them to do; parents'
      ideas about the age children can do activities, and the age they would allow
      their children to do them. This study described children's independent outdoor
      activities after-school, comparing age groups (school year 5 and 3), boys with
      girls, and the less socio-economically well off with the better off. METHODS: A
      cross-sectional study using questionnaires completed by 476 children aged seven
      and nine years and 471 parents in nine primary schools in Newcastle-upon-Tyne,
      England. RESULTS: Children reported they were permitted many outdoor activities
      such as cycling (78.8%), playing (78.6%) and roller skating in the street
      (62.7%). Parents of older children, boys, and more socio-economically deprived
      children were more likely than their comparison groups to allow children to do
      outdoor activities independently e.g. 34% of 9-year-olds were allowed to cross a
      road without an adult compared with 8% of 7-year-olds. Mostly, parents of boys
      and socio-economically deprived children, perceived children can do outdoor
      activities slightly younger than parents of girls and the socio-economically
      better off. CONCLUSION: Children and parents value and support children's
      independent outdoor activity. Differences in children's and parents'
      understanding of what activities are permissible and in their judgements about
      the appropriate age for children's independent activities, may partly underline
      variations by sex, age and socio-economic status in injury patterns.

PMID- 12073748
TI  - Hostility and the educational gradient in health. The mediating role of health
      related behaviours.
AB  - BACKGROUND: The aim was to study hostility as a factor intermediate in the
      association between educational level and health. METHODS: 1997 cross-sectional
      data from the Dutch GLOBE study (1675 men and 1819 women) was used. The analyses
      distinguishes between direct effects of hostility on health, and indirect
      effects, which are through health-related behaviours. The latter indicates that
      hostile people may be at risk of adverse health, because they engage in unhealthy
      behaviours. Data were analysed with logistic regression techniques. RESULTS:
      Among men and women, the odds of less than good health was higher in lower
      educational groups. A substantial part of the educational gradient in health
      could be ascribed to the intermediate effects of hostility. Among both men and
      women, the direct effects of hostility were more important than indirect effects.
      CONCLUSION: Results suggest that interventions should be aimed at the prevention
      of the development of hostility. Additionally, interventions aimed at the
      reduction of health damaging behaviours among adults may lead to a reduction of
      socio-economic inequalities in health.

PMID- 12073749
TI  - Late response and item nonresponse in the Finbalt Health Monitor survey.
AB  - BACKGROUND: The Finbalt Health Monitor is a collaborative system for monitoring
      the health-related behaviour, practices and lifestyles in Estonia, Finland,
      Latvia and Lithuania. This system is based on nationally representative samples
      and self-administered mailed questionnaires. In comparing the results of national
      surveys, the awareness of the direction and socioeconomic patterning of the
      response bias is essential. METHODS: The data were gathered from the cross
      sectional surveys conducted in 1998 from Estonia (n = 1362), Finland (n = 3504),
      Latvia (n = 2322) and Lithuania (n = 1874). An analysis was made of the
      prevalence of late response, completeness of information obtained from
      respondents and the magnitude of response bias on the prevalence estimates of
      health behaviour indicators. RESULTS: The response rates were comparatively high:
      68% in Estonia, 70% in Finland, 77% in Latvia and 62% in Lithuania. Late response
      was weakly related to age, education or place of residence. The total proportion
      of missing information was below 10% and the sociodemographic patterning for this
      missing information was similar in all countries. Thus, older and less-educated
      respondents had more missing information on their questionnaires. Response bias
      of the prevalence estimates was minimal when it was calculated by using
      information obtained from late respondents. CONCLUSIONS: The level of nonresponse
      and missing information was comparable in different countries, not information on
      health behaviour. Therefore special efforts are needed to design a questionnaire
      form which appears equally relevant to all respondent groups. The follow-up
      mailings were an effective way to increase the total response rate, but it was
      unlikely that they provided an effective way to reach the 'hard core'
      nonrespondents.

PMID- 12073750
TI  - Labour participation of the chronically ill. A profile sketch.
AB  - BACKGROUND: To improve our understanding of the problematic labour market
      position of people with a chronic disease, this paper describes the participation
      rates of several subgroups of the chronically ill in the Netherlands, as well as
      the aspects by which the working chronically ill differ from those who are fully
      work-disabled and from those who are not working for other reasons. METHODS: Data
      for this study are derived from the Panel of Patients with Chronic Diseases, a
      nationwide study in the Netherlands. The results discussed here relate to data
      collected in 1998 from a representative sample of 1266 people aged 15-64 with
      various chronic somatic diseases. The factors taken into account include medical
      diagnosis, disease duration, episodic occurrence and frequency of symptoms, pain,
      fatigue, functional disabilities with respect to motor control, somatic autonomy
      and cognitive autonomy, as well as the covariates gender, age and education.
      CONCLUSION: Labour market position is primarily related to health problems that
      can be considered common consequences of a chronic illness, while no independent
      effect of specific disease diagnosis was observed. In comparison with fully work
      disabled people, those who are employed experience less pain and fatigue and
      encounter fewer problems in motor control and cognitive functioning (besides
      being younger and more highly educated). The main factor besides gender, age and
      education, distinguishing employed from non-employed involves problems with motor
      control.

PMID- 12073751
TI  - Selection bias due to non-response in a health survey among patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Non-response may lead to bias in health(care) outcomes. METHODS: We
      compared respondents (n = 334) to a questionnaire survey among patients with
      rheumatoid arthritis with non-respondents (n = 68) and determined predictors of
      (non-)response. The bias in prevalence estimates of health characteristics and
      health care use was quantified. RESULTS: Self-reported pain and health care
      utilization were the most important predictors of (non-)response with respondents
      experiencing pain more often and more often using specific health care services.
      Bias concerned especially an underestimation of 'never having pain' (60%) and 'no
      contact with health care services' (51%). CONCLUSION: More insight into the
      phenomenon of non-response is important to assess disease burden and health care
      burden more precisely.

PMID- 12073752
TI  - New smokers and quitters. Transitions in smoking status in a national population.
AB  - BACKGROUND: Few studies have examined individual transitions in smoking status in
      national populations. METHODS: A representative sample of 21,970 men and women
      aged 15-64 were questioned regarding current smoking status and smoking status 12
      months ago. RESULTS: 1.56% of respondents had started to smoke and 1.58% had quit
      smoking. Becoming a smoker was significantly associated with younger age and
      lower social economic status (SES). Among women, many new smokers were between
      the age of 30 and 34, presumably due to relapse after pregnancy. High SES smokers
      quit at a younger age then lower SES groups. CONCLUSION: To reduce smoking
      prevalence in the Netherlands, more attention should be given to women aged 30-34
      years and to people from the lower SES groups, especially those under the age of
      45.

PMID- 12073753
TI  - Prevalence of tobacco and alcohol use disorders in Polish primary care settings.
AB  - BACKGROUND: Primary care settings are an ideal system in which to identify and
      treat tobacco and alcohol use disorders. This project surveyed patients from the
      offices of 20 Polish primary care clinicians to ascertain the prevalence of
      tobacco and alcohol use by gender and age. METHODS: A total of 4373 adults aged
      18-80 years seeking routine care completed a nurse-administered Health Screening
      Survey as part of a clinical trial designed to assess the efficacy of brief
      physician advice on heavy alcohol use. RESULTS: Of the 4373 subjects screened,
      44.4% reported cigarette use within the past three months. Most perceived smoking
      as a problem and had considered reducing their tobacco use. A stepwise model to
      examine factors that predict smoking status found that alcohol consumption was
      the best predictor of current cigarette use. Alcohol consumption was common, with
      64% of the subjects reporting some use within the previous three months. Of
      these, 55% were classified as low risk drinkers, 14% as at-risk drinkers, 12% as
      problem drinkers, and 19% as dependent drinkers. CONCLUSION: This is the first
      report on the combined prevalence of tobacco and alcohol use disorders in a
      sample of persons attending community-based primary care clinics in Poland. This
      report confirms the high prevalence of these problems and suggests that patients
      will accurately complete a screening test such as the Health Screening Survey.
      The methods employed for this study provide the Polish health care system with a
      procedure to effectively screen patients for tobacco and alcohol use disorders.

PMID- 12073754
TI  - Smoking-related costs among 25 to 59 year-old males in a 19-year individual
      follow-up.
AB  - OBJECTIVE: To estimate the health care expenditure and productivity losses due to
      smoking. DESIGN: A retrospective cohort study of a random population sample of
      5,247 men aged 25-59 years from the provinces of Kuopio and North Karelia in
      eastern Finland. Subjects initially surveyed in 1972 were linked to a set of
      national registers through their social security identification numbers and
      followed for 19 years. The difference in the number of life years and work years
      lost, the costs of drugs and hospitalization, and the value of productivity lost
      due to disability and premature mortality between smokers, former smokers and
      never-smokers was analysed. RESULTS: The difference in mean life expectancy
      between current smokers and never-smokers was 3.0 years, and the difference in
      mean lost work time was 2.6 years over the 19 years of follow-up. Between current
      smokers and former smokers, the difference in mean life expectancy was 1.8 years,
      and the difference in mean lost work time was 1.6 years. The mean difference
      between a current smoker and a never-smoker in health service costs was [symbol:
      see text] 2,900, and the difference in mean total costs was [symbol: see text]
      69,300 (an increase of 86%). No difference in mean health care costs between
      current smokers and former-smokers was found, while the difference in mean total
      cost was [symbol: see text] 44,000. CONCLUSIONS: Smokers incurred excess costs in
      terms of both direct health care expenditure and indirect productivity losses in
      comparison to the never-smoking population. Most importantly, quitting smoking
      could save at least 60% of the losses related to excess mortality and disability
      of smokers.

PMID- 12073755
TI  - BRIMHEALTH. A successful experience in Nordic-Baltic co-operation in public
      health training.

PMID- 12073756
TI  - The name of a drug used for the treatment of migraine.

PMID- 12073757
TI  - Third generation oral contraceptives and vascular risks.

PMID- 12073758
TI  - HIV prevention in prisons. Do international guidelines matter?
AB  - BACKGROUND: In spite of the availability of international guidelines, HIV
      prevention and management of care in prison is still unsatisfactory in many
      countries. Factors affecting the quality of HIV prevention policies in prison
      have not yet been elucidated. The present study had two aims: i) to assess
      national HIV prevention policies in prison in a selected group of countries; and
      ii) to determine which factors influenced such policies at the country level.
      METHODS: HIV prevention policies in prison were reviewed comparatively in
      Moldova, Hungary, Nizhnii Novgorod region of the Russian Federation, Switzerland
      and Italy. The review of HIV prevention policies in prison was conducted through
      interviews with government officials, non-governmental organizations,
      professionals involved in this field, and visits to selected prisons. Information
      on the health of prisoners, including tuberculosis, sexually transmitted
      diseases, and other infectious diseases has also been collected. RESULTS: The
      results indicated that all countries had adopted a policy, irrespective of the
      burden of HIV infection in the prison system. The content of the policy mirrored
      the philosophy and strategies of HIV prevention and care in the community. The
      1993 WHO Guidelines were fully implemented only in one country out of four
      (Switzerland), and partially in two (Italy and Hungary). CONCLUSIONS: A greater
      effort aimed at dissemination of information, provision of technical know-how and
      material resources could be the answer to at least part of the problems
      identified. In addition, greater national and international efforts are needed to
      stimulate the debate and build consensus on harm reduction activities in prison.

PMID- 12073759
TI  - Knowledge, attitudes and behaviour after 15 years of HIV/AIDS prevention in
      schools.
AB  - BACKGROUND: This paper reports efforts to estimate the results of the prevention
      policy of HIV/AIDS in young people, 15 years after the first case of AIDS in
      Greece by investigating the current level of knowledge, attitudes, beliefs,
      behaviour and practices of high school students towards HIV/AIDS. METHODS:
      Questionnaires from 702 students of 13 technical high schools in the Athens area
      were collected and analysed in 1997. RESULTS: 72% of the questions regarding
      knowledge were answered accurately. 43.15% of the participants believed that
      their knowledge about HIV/AIDS was sufficient. They considered AIDS to be a big
      threat to society (89.65%), and would be embarrassed if they were HIV positive
      (31.75%), however, they would be compassionate to HIV positive persons. One out
      of three were worried about already being HIV infected, because of their risky
      behaviour in the past, especially boys. The major change in their behaviour was
      the use of a condom (80.9% for boys and 56.7% for girls). 64.8% of the girls did
      not have sexual relations, while 41.9% of the boys had sexual relations with
      casual partners. CONCLUSION: After 15 years of prevention activities among young
      people, students have a satisfactory level of knowledge and have adopted
      relatively safe behaviour. However, boys, younger students, students with a high
      sense of religiousness and students with both excellent and low school records
      need more intense and systematic information through suitable interventions.

PMID- 12073760
TI  - Decentralization of the DOTS programme within a Russian penitentiary system. How
      to ensure the continuity of tuberculosis treatment in pre-trial detention
      centres.
AB  - BACKGROUND: In Kemerovo region (Siberia), three pre-trial detention centres
      (SIZO; Ministry of Justice) serve as the gateway to the penitentiary system,
      comprised of 23 prisons and 30,000 detainees. The follow-up for tuberculosis (TB)
      patients released into civil society is unreliable. Due to varying detention
      times and frequent transfers to temporary detention centres (IVS; Ministry of
      Internal Affairs) for investigation and trial, and concerns about continuity of
      treatment, SIZOs were not included in the revised TB control programme initiated
      during 1996. METHODS: To investigate the feasibility of DOTS (Directly Observed
      Therapy, Short-Course) expansion into SIZOs, general detainee release was studied
      by examining 10% of files from detainees admitted during 1998 (SIZOs 1,2,3).
      Then, 5% of general files from SIZO 1 were examined to determine SIZO-IVS flow;
      224 TB patient files from SIZO 3 were evaluated to determine the pattern of
      release/transfer. RESULTS: TB patients in SIZO 3 have less chance of release
      before six months of detention than non-TB detainees (14/224, 6.3% versus
      774/2276, 34%; p < 0.001). Among detainees not released, 60% are not moved during
      the first six months of detention. For those who move, the mean stay in IVS was
      9.5 (+/- 6) days. The incidence of active disease detected upon entry to SIZO 3
      was 4,560/100,000, the subsequent rate during the same year of detention
      880/100,000. CONCLUSION: Despite frequent detainee movements between
      institutions, DOTS should be introduced into the earliest stages of detention to
      prevent case mismanagement, and links to the civilian programme should be
      developed.

PMID- 12073761
TI  - Epidemiology of accidents among users of two-wheeled motor vehicles. A
      surveillance study in two Italian cities.
AB  - BACKGROUND: This paper describes a study on the epidemiology of accidents among
      users of two-wheeled motor vehicles in two Italian cities, Rome and Naples.
      METHODS: A surveillance study was conducted, recruiting the victims of accidents
      among users of two-wheeled motor vehicles, visiting the emergency departments of
      two Italian hospitals. The registration form includes personal data of the
      involved person, circumstances of the accident, means of arrival at the hospital,
      type of vehicles involved, helmet use, and eventually third parties involved, and
      data on the specific injury diagnosis. RESULTS: 736 injured drivers of two
      wheeled motor vehicles were investigated for the study (65.1% males, 34.9%
      females). The mean age of the victims was 22.92 years; 42.9% of the injuries were
      the result of a single accident. In 35.5% of the injuries cars were involved and
      in 8.6% of the cases there was a passenger included. Only 12% of the injured
      people were wearing a helmet. Most of the lesions concerns the knee or lower leg
      (27.5%), followed by the head (17.5%), elbow and forearm (8.8%), wrist and hand
      (8.6%), shoulder and upper arm (8.4%) and ankle and foot (6.9%). Helmet use has a
      protective effect (OR = 0.23), whereas accidents in Naples and during dark hours
      are associated with an increased risk of head injury (respectively OR = 1.93, and
      OR = 1.46). CONCLUSION: In this study the lower injury risk due to the use of the
      helmet on the frequency and severity of head trauma was confirmed. Moreover, the
      results confirm that Emergency Departments can provide essential epidemiological
      information, and they have already provided clear arguments in favour of
      extending the compulsory use of helmets to people above 18 years in Italy.

PMID- 12073762
TI  - Cardioprotection with white wine.
AB  - The cardioprotective effects of red wine have been attributed to several
      polyphenolic antioxidants including resveratrol and proanthocyanidins. The goal
      of the present study was to determine whether white wines could also provide
      cardioprotection. Three different white wines (white wine #1, #2 and #3) were
      chosen for this study. Ethanol-free extracts of the wines were prepared by vacuum
      evaporation. Rats weighing approximately 200 g were given either 50 mg/kg or 100
      mg/kg of each wine extract for 3 weeks. The rats were anesthetized and sacrificed
      and their hearts were excised for the preparation of isolated working rat heart.
      All hearts were subjected to 30 min of global ischemia followed by 2 h of
      reperfusion. Cardiac function including heart rate, left ventricular developed
      pressure (LVDP), maximum first derivative of developed pressure (LVdp/dtmax),
      left ventricular systolic pressure (LVSP), left ventricular end diastolic
      pressure (LVEP), aortic flow (AF) and coronary flow (CF) were continuously
      monitored and myocardial infarct size was measured at the end of the experiments.
      The results of our study demonstrated that among the three different white wines,
      only white wine #2 conferred cardioprotection as evidenced by improved
      postischemic ventricular recovery compared with controls. The same white wine at
      a dose of 50 mg/kg also showed improvement in postischemic contractile recovery
      but the differences compared with controls were not significant. The amount of
      malondialdehyde production from these hearts was lower than that found in control
      hearts, indicating reduced formation of reactive oxygen species in white wine #2
      treated rats. In vitro studies using a chemiluminescence technique revealed that
      white wine #2 scavenged both superoxide anions and hydroxyl radicals. The results
      of our study demonstrate that white wine #2 provided cardioprotection and the
      cardioprotective effect of the wine can be attributed, at least in part, to its
      ability to function as an in vivo antioxidant.

PMID- 12073764
TI  - Toxicological study of a glucose-added acetic acid maintenance infusion solution
      (VEEN 3G Inj.) local irritation test.
AB  - The local irritating effect of Veen 3G Inj. (glucose-added acetic acid
      maintenance infusion solution) was examined in male rabbits. We studied the local
      irritating effect of the infusion solution compared with that of Ringer's
      solution, 5% sulfobromophthalein sodium injection, distilled water for injection
      or glucose-added Ringer's solution. In the vascular irritation test,
      macroscopical and histopathological changes induced by the infusion solution were
      not observed in the vessels. Moreover, in the hemolytic test, hemolysis of rabbit
      erythrocyte was not observed in the mixture with the infusion solution. In the
      present study, no change suggesting irritation by the infusion solution was
      observed in the in vivo vascular irritation test using the auricular vein of
      rabbits or in the in vitro hemolytic test using rabbit erythrocyte. In
      conclusion, in clinical use the infusion solution produces extremely slight
      adverse effects, such as vessel pain and phlebitis on the injection site.

PMID- 12073763
TI  - Effect of some white wine phenols in preventing inflammatory cytokine release.
AB  - Some well-known antioxidant phenols present in extravirgin olive oil have also
      been found in white wine. Both tyrosol and caffeic acid are phenols that are
      present not only in extravirgin olive oil, but also in wine, especially white
      wine. Their antioxidant properties are well known, but their biological effects
      have not yet been elucidated. In a previous study we found that these substances
      were able to inhibit tumor necrosis factor alpha release. The present study was
      carried out to assess whether these compounds are able to inhibit other
      inflammatory cytokines, such as interleukin-1 beta and interleukin-6. The results
      show that low concentrations of these phenols, which can be found in the
      bloodstream after intake of moderate quantities of white wine, exert significant
      inhibitory activity on the release of several inflammatory cytokines.

PMID- 12073765
TI  - Decongestant activity of a new formulation of xylometazoline nasal spray: a
      double-blind, randomized versus placebo and reference drugs controlled, dose
      effect study.
AB  - Xylometazoline hydrochloride is an imidazoline derivative commonly used in
      topical application to relieve nasal congestion associated with acute or chronic
      rhinitis, common cold, sinusitis and hay fever or other allergies. To reduce the
      negative effects on the mucosal defensive mechanism, a new formulation of
      xylometazoline (Rhinostop) with inactive preservatives and hyaluronic acid (HA)
      was studied. The most appropriate concentration of xylometazoline and its
      decongestant activity in the new formulation were investigated in a double-blind,
      dose-effect study. The new formulation at three different concentrations of
      xylometazoline (0.025%, 0.05% and 0.1%) was compared with a placebo formulation,
      three equivalent aqueous solutions containing xylometazoline (without HA) and a
      reference formulation, containing benzalkonium chloride as preservative. The
      drugs' efficacy in reducing airflow resistance was also evaluated. The effects of
      xylometazoline on inspiratory and expiratory nasal resistance were found to be
      concentration-dependent. Indeed, the new formulation at a concentration of 0.05%
      was more effective than the new formulation at a concentration of 0.025%, but was
      statistically equivalent to the new formulation at a concentration of 0.1%;
      therefore, the 0.05% concentration of xylometazoline seemed to achieve maximal
      decongestant activity. These findings were confirmed by the observation that the
      efficacy of the new formulation at a concentration of 0.05% was also
      statistically comparable to that of the reference formulation and the aqueous
      solution of xylometazoline 0.1%. HA seems to act as an enhancer/carrier of the
      active principle, xylometazoline, as already demonstrated for other drugs. The
      new formulation at a concentration of 0.05% was therefore selected for further
      clinical development.

PMID- 12073766
TI  - Heparan sulfate in the treatment of intermittent claudication: results of a
      randomized, double-blind, placebo-controlled multicenter trial.
AB  - Peripheral arterial disease (PAD) is by far the most common cause of intermittent
      claudication. This disease can greatly reduce the affected individual's walking
      capacity and can seriously affect daily life activities. Few therapeutic options
      are aimed at improving walking capacity. This was a randomized, doubleblind,
      placebo-controlled, multicenter trial, performed in 24 Italian centers. Two
      hundred seventeen patients with intermittent claudication (stages IIa and IIb of
      Fontaine's PAD classification) were randomly assigned to heparan sulfate (40 mg
      orally twice a day) or placebo for 6 months. The primary end-point was an
      increase in pain-free walking distance [initial claudication distance (ICD)]
      during the 24 weeks of treatment. The pain-free and the absolute walking distance
      (ACD) were monitored by standardized treadmill test at baseline and at 4, 12 and
      24 weeks. The change in initial claudication distance during treatment, expressed
      as integrated change over time, was significantly greater with heparan sulfate
      than with placebo (306 +/- 494 vs. 250 +/- 510 meters x months, p = 0.019).
      Significantly fewer treated patients worsened during treatment (decreased initial
      claudication distance) compared with controls (9.1% vs. 19.6%; p = 0.027).
      Functional recovery in the most severely affected subgroup of patients (stage IIb
      of Fontaine's classification) was more clearly detected and significantly greater
      among treated than among control patients (absolute increase in ICD: 70 +/- 113
      vs. 58 +/- 172 meters, p = 0.028; integrated increase: 304 +/- 422 vs. 208 +/-
      503 meters x months; p = 0.004). Heparan sulfate appeared to increase the walking
      capacity of patients with intermittent claudication to a significantly greater
      extent than did placebo. The treatment was well tolerated.

PMID- 12073767
TI  - Differential display of m-RNAs in fish gonads by modified DD-PCR.
AB  - In a previous report we presented a modification of the original Differential
      Display PCR technique using a single oligo (dT) primer for the reverse
      transcription reaction (instead of the various oligo (dT)NM primers that
      subdivide the pool of mRNAs) and a combination of 25-mer or 26-mer arbitrary
      primers together with 30-mer anchored primers for the PCR reaction. The PCR
      products were, then, efficiently separated in a nondenaturing polyacrylamide gel
      and the bands were visualized after staining with silver nitrate. In this report
      we extended our studies and we used fish gonads from various fish as the model to
      trace the differential expression of mRNAs, which were isolated by various
      methods. Since xenoestrogens are toxic to the gonads of many fish, we tried to
      set up the conditions in order to further characterize genes that are markers of
      exposure to xenoestrogens.

PMID- 12073768
TI  - Physical performance and prediction of 2-5A synthetase/RNase L antiviral pathway
      activity in patients with chronic fatigue syndrome.
AB  - The elevated RNase L enzyme activity observed in some Chronic Fatigue Syndrome
      (CFS) patients may be linked to the low exercise tolerance and functional
      impairment that typify this disease. The purpose of this investigation was to
      determine if specific indicators of physical performance can predict abnormal
      RNase L activity in CFS patients. Seventy-three CFS patients performed a graded
      exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L
      levels. This measure was employed as the dependent variable in a discriminant
      function analysis, with peak V02, exercise duration and Karnofsky Performance
      Scores (KPS) serving as the independent variables. All three variables entered
      the single significant function (p < 0.001). The elevated RNase L group had a
      lower peak V02 and duration than the normal group, but a higher KPS. The results
      suggest that both exercise testing and the RNase L biomarker have potential to
      aid in the diagnosis of CFS.

PMID- 12073769
TI  - Computer simulation of spermine-porin channel interactions.
AB  - Porin channels play a prominent role during fluoroquinolone uptake and spermine
      strongly alters the diffusion rate of norfloxacine. Consequently the interactions
      between spermine and bacterial porin were studied by computer simulation. The
      results indicate that various residues (E62, D 113, E 117,...) closely located in
      the internal eyelet region of the OmpF channel are potential binding sites. Among
      them, the D 113 residue, seems to play an important role in the association
      channel-spermine. This interaction introduces several changes in the internal
      morphology of the channel which are responsible for the inhibition of antibiotic
      uptake using the porin route.

PMID- 12073770
TI  - A multi-resistant Acinetobacter baumannii outbreak in a general intensive care
      unit.
AB  - In an Intensive Care Unit, three patients were found infected and two colonized
      with multiresistant Acinetobacter baumannii within a period of one week. To
      identify the outbreak source, two surveillance studies were performed concerning
      patients and the environment. Genotyping of isolates was performed by random
      amplification of polymorphic DNA analysis (RAPD). Environmental sampling failed
      to yield A. baumannii, with the exception of a single sample from a trunking.
      RAPD-fingerprinting yielded identical patterns for all patient isolates including
      the trunking isolate, thus confirming the suspected cluster. Since the strain
      from the trunking had a susceptibility pattern and a RAPD pattern identical to
      that of the strains isolated from the patients, we believe that this was the
      likely source of the outbreak. In conclusion, A. baumannii outbreaks may be
      quickly controlled by appropriate action of the hospital infection staff. RAPD
      fingerprinting may provide a useful and rapid identification technique for the
      epidemiological investigation of a hospital outbreak.

PMID- 12073771
TI  - The subepithelial band in collagenous colitis is autofluorescent a study in H&E
      stained sections.
AB  - The normal basement membrane (BM) of the colon and the collagenous colitis band
      (CCB) seen in H&E-stained sections were recently found to be autofluorescent.
      Measurements of the thickness of the BM and of the CCB were taken using
      transmitted-light (TL) and incident-light fluorescence (IFL). The mean thickness
      of the BM in control cases was 3.2 microns with TL and 3.4 microns with IFL. The
      mean thickness of the CCB was 50.3 microns with TL and 55.8 microns with IFL. In
      10 consecutive cases of CC, the thickness of the CCB was repeatedly measured in
      the same area, on different occasions. Substantial variations in the vertical
      size of the CCB were recorded in the same area when using TL but not with IFL.
      Good demarcation of the CCB with ILF and poor demarcation of the deep border of
      the hyaline band, because of overlapping inflammatory cells, were the apparent
      causes. Autofluorescence was induced by the eosin stain. The results suggest that
      the simple observation of H&E--stained biopsies with ILF may be sufficient to
      diagnose CC. Re-sectioning for special staining can be avoided, thus reducing
      final diagnosis-time and laboratory costs.

PMID- 12073772
TI  - Restoration of the thymic cellular microenvironment following autologous bone
      marrow transplantation.
AB  - Mammalian thymic histogenesis can be morphologically divided into three
      consecutive stages: 1) epithelial; 2) lymphopoietic or lympho-epithelial; and 3)
      differentiated cellular microenvironmental, with formation of Hassall's bodies
      (HBs). The marked reduction of the thymic cellular microenvironment (TCM) is a
      well-controlled physiological process and is presumably under both local and
      global regulation by the cells of the RE meshwork and by the neuroendocrine axis,
      respectively. In humans, the age-related decline of facteur thymique serique
      (FTS) levels in blood begins after 20 years of age and FTS completely disappears
      between the 5th and 6th decade of life. In contrast, serum levels of thymosin
      alpha 1 and thymopoietin seem to decline earlier, starting as early as 10 years
      of age. The influences of other hormones on the thymic involution have also been
      characterized: testosterone, estrogen and hydrocortisone treatment results in
      marked involution, cortisone and progesterone administration causes slight to
      moderate, while use of desoxycorticosterone has no effect. Since the thymus is
      the primary T-lymphopoietic organ during mammalian ontogenesis, its age-related
      involution with the typical immunomorphological alterations can be held
      responsible only for a decline in antigen-specific T-lymphocyte immune functions.
      Thymic involution and diminished T-lymphocyte proliferation can be partially
      restored by thymic tissue transplantation or administration of thymic hormones.
      The stimulus for thymic cell proliferation and differentiation is genetically
      determined within the organ implant. The only partial reconstitution of CD4+ T
      helper-lymphocyte subset after anti-neoplastic chemotherapy and autologous BTM
      represents a significant, therapy-complicating, clinical problem. After high-dose
      chemotherapy, the restoration of thymus-dependent CD4+ T-lymphocyte genesis was
      reported only in children. Our radiation, stem cell transplantation, and hormone
      treatment experiments in animals resulted in age- and time-dependent regeneration
      of the cytoarchitecture of the TCM, as well as intrathymic lymphopoiesis.

PMID- 12073773
TI  - Proliferative activity (Ki-67), WT p53, Bcl-2 expression and their relationship
      to the tumor grade, in invasive ductal breast carcinomas.
AB  - To study the relationship between the expressions of Ki-67, WT p53, Bcl-2
      proteins and tumor grade, on fine needle aspiration biopsies (FNABs), in patients
      with invasive ductal breast carcinomas. One hundred (100) FNABs were performed
      from the same number of female patients, diagnosed cytologically and confirmed
      histologically after oncectomy. The same cases were studied immunocytochemically
      using the monoclonal antibodies Ki-67, WT p53 and Bcl-2 by the alkaline
      phosphatase (APAAP) method and correlated to the nuclear and histological grade
      of the tumors. An association and a relationship was found between the grade of
      the tumors and the immunoexpression of Ki-67, WT p53 and Bcl-2 proteins (p <
      0.005). The relationship between Ki-67, WT p53 and Bcl-2 proteins and the grade
      of the invasive ductal breast carcinomas seems to be a significant prognostic
      factor and should be kept in mind in follow-up patients after previous treatment
      for breast cancer.

PMID- 12073774
TI  - Prevention/reversal of choline deficiency-induced steatohepatitis by a peroxisome
      proliferator-activated receptor alpha ligand in rats.
AB  - Nonalcoholic steatohepatitis, often associated with obesity and diabetes, is a
      common liver condition in the U.S. Individuals with steatohepatitis are not
      eligible for liver donation and may be at increased risk from developing
      complications following lobectomy. If steatosis and steatohepatitis can be
      treated medically, these individuals can become eligible for living donor
      transplants and segmental resection of the liver for treatment of primary or
      metastatic liver diseases. Because rats fed a choline-deficient diet (CDD)
      develop morphological changes in the liver similar to that observed in
      nonalcoholic steatohepatitis, we examined the effect of ciprofibrate, a potent
      peroxisome proliferator activated receptor alpha (PPAR alpha) ligand and inducer
      of fatty acid oxidation systems in the liver, on reversal of steatosis. Rats fed
      CDD for 2 weeks developed marked fatty change with mild hepatitis and marked
      increase in serum aminotransferases and liver triacylglycerols. Concurrent
      administration of CDD and ciprofibrate resulted in the prevention of fatty
      change. Rats that were fed CDD for 2 weeks followed by feeding CDD containing
      ciprofibrate for 1 or 2 weeks resulted in marked reduction of fatty change and
      normalization of serum aminotransferases. Compared with the CDD group, all groups
      that received ciprofibrate showed several-fold increase in mRNA and protein
      levels of several PPAR alpha target genes. In addition, electron microscopic
      examination showed marked peroxisome proliferation in the hepatocytes. The
      results of these studies clearly demonstrate that the severity of CDD-induced
      fatty change and hepatitis in rats can be rapidly decreased by ciprofibrate and
      suggest the therapeutic potential of PPAR alpha ligands in the treatment of
      nonalcoholic steatohepatitis in humans to rapidly reverse liver changes.

PMID- 12073775
TI  - Biologically relevant orthotopic neuroblastoma xenograft models: primary adrenal
      tumor growth and spontaneous distant metastasis.
AB  - To provide investigative tools for the study of neuroblastoma (NB) biology and
      therapy, we have characterized five orthotopic (adrenal) human xenograft models
      of NB. Initial experiments compared subcutaneous (heterotopic) with adrenal
      (orthotopic) injections of two NB cell lines (SK-N-AS and SMS-KCNR) in Beige-SCID
      mice. These studies demonstrated more relevant tumor biology, including
      angiogenic phenotype, and enhanced spontaneous distant metastasis for orthotopic
      versus heterotopic tumors. RNase protection assay demonstrated differences in the
      expression of angiogenesis-associated genes (flt1, TIE1, angiopoietin, and
      endoglin) between adrenal and subcutaneous xenografts. Orthotopic models were
      used to define and characterize the three remaining NB cell lines (SH-SY5Y, LA-1
      15N, and IMR32). The pattern of angiogenesis was distinctive for each xenograft
      model and included a variety of vascular structures. The sites for metastases
      were distinct for each cell line and included lymph nodes, liver, ovaries, lungs,
      bone marrow and local bone extension. These well characterized, relevant, highly
      angiogenic, and metastatic orthotopic models of NB will be a valuable resource to
      improve our understanding of the biology and treatment of NB.

PMID- 12073776
TI  - Dynamics of HTLV-1 leukemogenesis: data acquisition for computer modeling.
AB  - A literature search for HTLV-1-induced adult T-cell leukemia (ATL) at the
      National Library of Medicine resulted in 1003 publications which were evaluated
      with regard to HTLV-1 virus load, apoptosis and peripheral blood leukocyte
      changes during the latent period and leukemia development following virus
      infection. The data are presented in a comparable way to previous publications of
      infections with HHV-6 and HIV (which target the same CD4+ cell for infection) to
      be used for computer validation studies. After initial infection, HTLV-1 remains
      clinically latent for many years at low provirus copy numbers in CD4 cells. Once
      immune surveillance deteriorates and viral replication progresses, provirus copy
      numbers increase rapidly. Unlike other virus infections, apoptotic death of virus
      infected "atypical" lymphocytes decreases with increasing viral load, thus
      favoring continued proliferation of these cells and further virus replication at
      the same time. Changes in the peripheral blood are characterized by coincident
      rises in oligoclonal lymphocyte populations including HTLV-1-positive CD4+ T
      lymphocytes and their precursors with a progressive shift to immature cells as
      disease progresses. The pathogenesis of HTLV-1-induced adult T-cell leukemia is
      an example of dysregulative leukemogenesis ideal for validation of respective
      computer simulation models.

PMID- 12073777
TI  - A phase II study of chemoneuroimmunotherapy with platinum, subcutaneous low-dose
      interleukin-2 and the pineal neurohormone melatonin (P.I.M.) as a second-line
      therapy in metastatic melanoma patients progressing on dacarbazine plus
      interferon-alpha.
AB  - Immunochemotherapeutic combinations containing IL-2 theoretically represent the
      most effective therapies for metastatic melanoma, particularly in association
      with cisplatin (CDDP); however, both IL-2 and CDDP have been generally utilized
      at high doses, with the consequence of considerable toxicity. According to
      psychoneuroimmunological knowledge, the antitumor activity of IL-2 has been
      proven to be enhanced by the immunomodulating pineal neurohormone melatonin
      (MLT), which has also been shown to increase the cytotoxicity of cancer
      chemotherapy and reduce its toxicity. On this basis, a study was planned with low
      dose IL-2 and CDDP in association with MLT as a second-line therapy for
      metastatic melanoma patients progressing on dacarbazine plus interferon-alpha.
      The study included 13 evaluable patients. CDDP was injected i.v. at 30 mg/m2/day
      for 3 days every 21 days. IL-2 was administered s.c. at 3 million IU/day from
      days 4 to 9 and from days 11 to 16 of the cycle. Finally, MLT was given orally at
      20 mg/day in the evening, every day without interruption. One patient obtained a
      complete response (CR), while partial response (PR) was achieved in 3 other
      patients. Therefore, the objective tumor response-rate (CR + PR) was 4 out of 13
      (31%). A stable disease occurred in 5 patients, whereas the remaining 4 patients
      had a progressive disease. The treatment was extremely well-tolerated in all
      patients and, in particular, no CDDP-related neurotoxicity was observed. The
      results of this preliminary study would suggest that low-dose CDDP and IL-2 in
      association with the pineal hormone MLT (P.I.M. schedule), given as a second line
      therapy, is an effective and well-tolerated treatment for metastatic melanoma,
      with a clinical efficacy at least comparable to that obtained with a first-line
      therapy of dacarbazine plus interferon-alpha.

PMID- 12073778
TI  - Trifluoromethyl ketones show culture age-dependent inhibitory effects on low K(+)
      induced apoptosis in cerebellar granule neurons.
AB  - We previously reported that two trifluoromethyl ketones, 3,3,3-trifluoro-1-phenyl
      1,2-propanedione (TF1) and 1,1,1-trifluoro-3-phenyl-2-propanone (TF2), have
      neuroprotective effects against low K(+)-induced apoptosis in cerebellar granule
      neurons (CGNs) exposed at 12-13 days in vitro (DIV). On the other hand, these
      compounds showed weak neuroprotective potency against 7 DIV CGNs. It is reported
      that actinomycin D (Act-D), cycloheximide (CHX), and caspase-3 inhibitors prevent
      the apoptosis of CGNs induced by K+ deprivation. However, these experiments are
      generally performed using 7 DIV CGNs. We investigated and compared the
      antiapoptotic efficacy of these drugs and newly-discovered TF1 and TF2 to protect
      DIV 7 and 12-13 CGNs from death induced by K+ deprivation. Apoptosis of CGNs
      induced by K+ withdrawal at 13 DIV was potently inhibited by Act-D and CHX
      similar to those at 7 DIV. Caspase-3 inhibitors moderately suppressed cell death
      during low K(+)-induced apoptosis both exposed 7 and 13 DIV. Serine protease
      inhibitor N-tosyl-L-phenylalanyl chloromethylketone (TPCK) had no effect on K(+)
      deprivation-induced apoptosis of CGNs at both 7 and 12 DIV. This study showed
      that there are different pathways of apoptosis in CGNs depending on the culture
      age.

PMID- 12073779
TI  - [Treatment of equine sarcoids with cisplatin in arachid oil: a useful
      alternative?].
AB  - At the Department of Equine Sciences at Utrecht University a study was performed
      on the treatment of sarcoids with the cytostatic drug cisplatin. Fourteen horses
      with 23 sarcoids were treated in the period 2000-2001. Complete regression was
      seen in 78% of the tumours. No systemic side-effects were encountered. Although
      treatment was easy to perform, the ALARA (As Low As Reasonably Achievable)
      principle should be followed when using cytostatics.

PMID- 12073780
TI  - [Biotechnology: hail to man and animal].
AB  - There are two basic remarks that must be made about this series of articles on
      the theme 'Modern biotechnology: a blessing or concern?'. Firstly, it is
      difficult to define what 'biotechnology' is due to the diversity of techniques
      employed. Secondly, it is striking how biotechnological techniques may be
      employed for such a wide variety of goals. In this article, the ethics of using
      biotechnology within veterinary science and research will be discussed. Aside
      from its usefulness to humankind, an animal has its own value as a living
      creature; a fact that we should always take into account. Ethical issues such as
      the health, welfare and integrity of animals are discussed here in relation to
      developments in biotechnology. These ethical arguments reveal that biotechnology
      does not always have a positive impact on animals. This does not necessarily mean
      that biotechnology should be rejected out of hand, but that it is essential that
      the purpose for which the animals are being used be adequately justified. In this
      regard, the veterinarian may play a unique role as the guardian of both animal
      and human health. The veterinary profession, in all its diversity, is a
      participant in the development and (future) practical application of
      biotechnological techniques. Changes in the broader society and within the
      veterinary profession may continue to play a role in the societal discourse on
      biotechnology and its practical application, it must actively consider the
      ethical aspects and consequences of these scientific developments.

PMID- 12073781
TI  - [Dog with leishmaniasis].

PMID- 12073782
TI  - [Animals go to the veterinarian, people go to the dentist].
AB  - The Dutch law and other regulations provide that only registered veterinarians
      can treat animals. Moreover, by law only registered individuals may use the title
      veterinarian or dentist. The veterinary professional should be open to advice,
      help, and technical assistance from other professionals working with human or
      animals patients. The dental treatment of animal patients must not be carried out
      in a dental surgery or hospital used by human patients.

PMID- 12073783
TI  - [Dear editors: non-vaccination management].

PMID- 12073784
TI  - [She does behave funny, but she is no 'crazy cow' (BSE)].
AB  - Since 1999 18 cows with 'crampiness' were presented for clinical inspection. Most
      animals were called upon because of clinically 'suspected BSE' by the local
      veterinary practitioner. The clinical picture of the disease and the differences
      with BSE are discussed.

PMID- 12073786
TI  - [The European Zoo Nutrition Center].

PMID- 12073785
TI  - [Comparison of long term side effects of ovariectomy versus ovariohisterectomy in
      the bitch].

PMID- 12073787
TI  - [Image of the month. A tumor of the scalp revealing a nevoid basocellular
      carcinoma].

PMID- 12073788
TI  - [How I treat ... surgically benign uterine lesions in 2002].
AB  - For 20 years, pre-operative investigations have increasingly improved the
      gynaecological diagnosis, allowing to have an accurate idea on the size and the
      nature of the lesion to be treated when the matter is to carry out the surgical
      treatment. In the meantime, the gynaecological surgery has seen its endoscopic
      surgical techniques improved due to the development of these diagnostic
      techniques itself. The operative hysteroscopy allows to decrease considerably the
      amount of hysterectomies for benign lesions. The operative laparoscopy has become
      the first intended treatment for many pathologies. This latter allows performing
      either laparoscopic assisted vaginal hysterectomies or complete laparoscopic
      hysterectomies. On the other hand, even though these endoscopic techniques were
      developing, the vaginal hysterectomy strongly returned, in such a way that it
      became the dominating way, so that the rule is to perform abdominal hysterectomy
      only when it is impossible to carry out a low way hysterectomy. Consequently, the
      gynaecologist surgeon has to be capable, in 2002, to perform all these surgical
      techniques in order to offer to the patient the best treatment, matching as good
      as feasible according to the pathology to be treated and her anatomical status.

PMID- 12073789
TI  - [Clinical case of the month. Myoclonic-astatic epilepsy in a young child (MAE) or
      Doose syndrome].
AB  - Myoclonic astatic epilepsy (MAE) belongs to the epilepsies with generalized
      seizures. MAE occurs in 1-2% of all childhood epilepsies up to age 9. This
      disease is characterized by various clinical and EEG criteria. The course of this
      epileptic syndrome is variable but influenced by an early diagnosis and by a
      specific treatment.

PMID- 12073790
TI  - [Postprandial hyperglycemia. II. Pharmacological approaches].
AB  - Besides dietary approaches, various pharmacological means have been recently
      developed in order to better control postprandial hyperglycaemia. This objective
      may be obtained: 1) by slowing down the intestinal absorption of carbohydrates;
      2) by insuring a better insulin priming soon after the meal; and 3) by inhibiting
      post-prandial glucagon secretion or action. Some hormones (amylin, glucagon-like
      peptide-1) can slow gastric emptying while alpha-glucosidase inhibitors
      (acarbose, miglitol) retard intestinal digestion and resorption of complex
      carbohydrates. A more physiological post-meal profile of insulin may be obtained
      in type 2 diabetes by using new insulin secretagogues of the glinide family
      (repaglinide, nateglinide) with an earlier and shorter insulinotropic action or,
      mainly in type 1 diabetes but also in type 2 diabetes, by using short-acting
      insulin analogues (lispro. Asp B28) or inhated insulin the action of which is
      faster than that of subcutaneous insulin. Post-prandial glucagon secretion can be
      inhibited by amylin. GLP-1 or insulin while other glucagon antagonists are
      currently in development.

PMID- 12073791
TI  - [Quality of hypertension management. Can we, must we do better?].
AB  - Hypertension is well controlled in only less than 30% of the patients treated by
      drugs. It is thus important to improve this situation first by checking the
      treatment compliance but also by trying to better educate the hypertensive
      population about the risk of uncontrolled hypertension and how to decrease this
      risk.

PMID- 12073792
TI  - [Preventive cardiology: strategies in children].
AB  - The importance of preventive cardiology in youth has been established by several
      critical observations: there is evidence that the atherogenic process begins in
      childhood, and that the degree of atherogenesis is related to measurable risk
      factors present during childhood. The literature indicated that long-range
      prevention of atheroselerosis and its sequelae by control of those risk factors
      should begin in childhood. This article reviews the established risk factors, the
      identification of high-risk individuals, public health strategies for the
      promotion of health in the French Community of Belgium and treatment of high-risk
      individuals.

PMID- 12073794
TI  - [Percutaneous tracheotomy: personal contributions to the technique].
AB  - We developed within our service of intensive care a hybrid procedure combining
      the advantages of the techniques of Caglia and Fantoni. Ventilation downstream
      from the site of dilatation, thanks to a longer tracheal tube of small diameter,
      ensures an optimal spirometry and reduces to a minimum the time of apnea. It
      decreases the risks of per-operational subcutaneous emphysema. A system of camera
      video assembled on a flexible fibroscope allows a direct vision on television
      screen. The operator can, constantly, visualise his gesture in one glance, in
      real time. Such an approach increases the security and the effectiveness of the
      method. The procedure remains nevertheless simple and does not require a thorough
      experience in percutaneous dilatational tracheotomy.

PMID- 12073793
TI  - [Still's disease in the adult].
AB  - The Adult Onset Still's Disease (AOSD) is an entity of unknown origin
      characterised by fever, polyarthralgias or polyarthritis, a pharyngitis, a
      cutaneous eruption and elevation of leucocytes. We present observations of 17
      patients diagnosed during the last thirteen years. Files of hospitalized patients
      with suspected AOSD have been examined in a retrospective study and Yamaguchi and
      Kahn's criterias applied in order to confirm the diagnosis. Treatments undertaken
      and the evolution have been noted. The sex ratio is 1.83; the middle age of
      intervening from 42 to 45 years. The middle delay for the diagnosis is 3 to 8
      weeks. Fever, eruption and polyarthralgias are the most frequent clinical signs.
      Elevation of leucocytes, hepatic cytolysis and hyperferritinemia are usual.
      Constantly, inflammatory tests are increased and the rheumatoid factor and the
      antinuclear antibodies are negative. Yamaguchi's criterias have been met by all
      patients. The non steroid anti-inflammatory drugs and corticoids constituted the
      main treatment. In the evolutionary shield, 6 cases of remission have been noted.
      The other patients evolved toward the chronicity with either a systemic or an
      articular shape. In the two situations, a state of corticodependance got settled
      with necessity of association to immunosuppressive drugs. The diagnosis of AOSD
      is easily done on basis of Yamaguchi's criterias. Corticoids can permit to
      control the bouts. There are 3 types of evolution: remission, chronic systemic or
      chronic articular shape.

PMID- 12073795
TI  - [Clinical characteristics and sputum cytology of intrinsic asthma].
AB  - The diagnosis of intrinsic asthma is evoked in patients with clinical criteria of
      asthma but, who contrarily to atopic asthmatics, lack history of allergy,
      specific IgE and skin positive reaction towards common aeroallergens of the
      environment. While the bronchial cytology of these two types of asthma is
      comparable, the immunological mechanisms of intrinsic asthma remain poorly
      understood because the factors responsible for the bronchial inflammation are
      unknown. Intrinsic asthma normally begins in adulthood and carries often a more
      severe prognosis. This disease is more frequent in women and is often associated
      to nasal polyposis and/or aspirin hypersensitivity. In this work, we have
      retrospectively studied the demographic and clinical characteristics, as well as
      the lung function and the sputum cell counts of intrinsic asthmatic outpatients
      seen during the period of 1996 to 1998 in the Pneumology Department of the CHU
      Sart Tilman.

PMID- 12073796
TI  - [Corneal ulcers associated with rheumatoid arthritis].
AB  - Keratoconjonctivitis sicca, scleritis and keratitis remain the major ocular
      manifestation, associated with rheumatoid arthritis. Corneal ulcers are a rare
      complication but can lead to perforation. Unstable epithelial barrier and immune
      disorders play a key role in the pathophysiology of such corneal melting.
      Moreover the association with systemic vasculitis reveals the need for an
      appropriate immunosuppressive treatment. New surgical approaches and early
      immunotherapy allow to maintain ocular integrity even if the visual prognosis is
      poor.

PMID- 12073797
TI  - [Green nail syndrome or chloronychia].
AB  - "Green nails" or chloronychia is an infection mostly caused by Pseudomonas
      ueruginosa but also by other bacterial or fungal contamination. The clinical
      appearance consists in a typical triad: green discoloration of the nail plate
      associated with proximal chronic paronychia and disto-lateral onycholysis.
      Exposition to moist environment, microtraumatisms, oaychotillomania and
      associated nail diseases such as psoriasis may promote infection by Pseudomonas.
      Treatment consists in cutting of the detached nail plate, brushing the nail bed
      with a 2% sodium hypochlorite solution twice daily and eviction of the repeated
      immersions by wearing cotton and latex gloves.

PMID- 12073798
TI  - [Medication of the month. Rosiglitazone (Avandia)].
AB  - Rosiglitazone (Avandia, Glaxo-SmithKline) belongs to a new family of oral
      hypoglycaemic agents, thiazolidinediones or glitazones. These molecules act as
      selective agonists of nuclear receptors (PPAR gamma) and improve insulin
      sensitivity. In Belgium as in all European countries, rosiglitazone is indicated
      for the treatment of type 2 diabetes, only in combination with another
      antidiabetic oral agent, in patients insufficiently controlled with metformin or
      a sulphonylurea at a maximal tolerated dose. In these patients, rosiglitazone, at
      a daily dose of 4 mg (sometimes 8 mg/day with metformin), reduces fasting
      glycaemia by 2-3 mmol/l and glycated haemoglobin level by about 1%. It exerts
      also favourable effects on some risk factors related to insulin resistance
      syndrome, which may contribute to improve cardiovascular prognosis of patients
      with type 2 diabetes. Hepatic safety of rosiglitazone seems to be good, although
      it is still recommended to check liver enzymes regularly. As all glitazones,
      rosiglitazone moderately promotes weight gain. It can also induce some fluid
      retention which may reveal or aggravate heart failure in at risk patients.

PMID- 12073799
TI  - [Clinical study of the month. The LIFE study: cardiovascular protection of
      hypertensive patients by losartan].
AB  - The LIFE study ("Losartan Intervention For Endpoint reduction in hypertension
      study") demonstrated a significant cardiovascular protection by an angiotensin
      AT1 receptor antagonist, losartan, in hypertensive patients with left ventricular
      hypertrophy. At similar blood pressure control, losartan, as compared to
      atenolol, reduced the relative risk of primary cardiovascular event (death,
      myocardial infarction, or stroke) by 13% (p = 0.021) in the whole cohort of 9.193
      patients after a mean follow-up of 4.7 years. In a subgroup of 1.195 diabetic
      patients, the protection was even more marked with a reduction of the combined
      risk of 24% (p = 0.031) and a fall of the mortality of 39% (p = 0.002). In
      conclusion, losartan prevents cardiovascular morbidity and death more effectively
      than atenolol, and seems to confer benefits beyond reduction in blood pressure.

PMID- 12073800
TI  - Beauty from brokenness.

PMID- 12073801
TI  - How to implement evidence-based practice.

PMID- 12073802
TI  - Putting research into practice.

PMID- 12073804
TI  - Evidence-based nursing: perspective from Pakistan.

PMID- 12073803
TI  - Evidence-based practice: an administrative perspective.

PMID- 12073805
TI  - Evidence-based practice: a modern U.K. phenomenon.

PMID- 12073806
TI  - Using existing databases for product evaluation: silver-treated catheter trial.

PMID- 12073807
TI  - Evidence-based development of a hospital-based heart failure center.

PMID- 12073808
TI  - Developing an organized system of care for college students with alcohol abuse
      and alcohol dependence.

PMID- 12073809
TI  - Using a FOCUS-PDCA quality improvement model for applying the severe traumatic
      brain injury guidelines to practice: process and outcomes.

PMID- 12073810
TI  - Cardiac surgery in an era of antiplatelet therapies: generating new evidence.

PMID- 12073811
TI  - Price survey. PTCA prices still moving down.

PMID- 12073812
TI  - Senate subcommittee hears GPOs and critics.

PMID- 12073813
TI  - Prices will edge upward for many supplies.

PMID- 12073814
TI  - Price hikes will herald economic growth.
AB  - Economic growth will continue in the second half of 2002, according to the
      semiannual forecast of the Institute for Supply Management (ISM). Prices will
      rise, too, the managers predict.

PMID- 12073815
TI  - GPOs need new policies and strategies.
AB  - Hospital and health care system CEOs who sit on the boards of the industry's
      group purchasing organizations must make some major changes in how GPOs are
      governed and operated.

PMID- 12073816
TI  - Ecophysiology and breeding of mycoparasitic Trichoderma strains (a review).
AB  - Losses due to plant diseases may be as high as 10-20% of the total worldwide food
      production every year, resulting in economic losses amounting to many billions of
      dollars and diminished food supplies. Chemical control involves the use of
      chemical pesticides to eradicate or reduce the populations of pathogens or to
      protect the plants from infection by pathogens. For some diseases chemical
      control is very effective, but it is often non-specific in its effects, killing
      beneficial organisms as well as pathogens, and it may have undesirable health,
      safety, and environmental risks. Biological control involves the use of one or
      more biological organisms to control the pathogens or diseases. Biological
      control is more specialized and uses specific microorganisms that attack or
      interfere with the pathogens. The members of the genus Trichoderma are very
      promising against soil-born plant parasitic fungi. These filamentous fungi are
      very widespread in nature, with high population densities in soils and plant
      litters [1]. They are saprophytic, quickly growing and easy to culture and they
      can produce large amounts of conidia with long lifetime.

PMID- 12073817
TI  - Gibberellin and auxin-indole production by plant root-fungi and their
      biosynthesis under salinity-calcium interaction.
AB  - Rhizosphere and rhizoplane of fababean (Vicia faba), melochia (Corchorus
      olitorius), sesame (Sesamum indicum) and soyabean (Glycine max) plants are
      inhabited with fungi, mostly Aspergillus flavus, A. niger, Fusarium oxysporum,
      Penicillium corylophilum, P. cyclopium, P. funiculosum and Rhizopus stolonifer.
      All fungal species have the ability to produce gibberellin (GA) but F. oxysporum
      was found to produce both GA and indole-acetic acid (IAA). The optimum period for
      GA and IAA production by F. oxysporum was 10 days in the mycelium and 15 days in
      the filtrate at 28 degrees C. The contents of GA, IAA and cytochrome P-450 were
      increased at 0.5 and 1% NaCl after 5 days, but GA and IAA were lowered at 4% (700
      mM) NaCl. Calcium decreased NaCl stress on F. oxysporum by significant elevating
      GA biosynthesis at 40 mM Ca2+/700 mM Na+. GA at 10 microM and Ca2+ at 10 mM
      enhanced the germination of seeds under 175 mM Na+.

PMID- 12073818
TI  - Identification of enterococci isolated from cow's milk cheese: comparison of the
      classical methods and the API 20 STREP system (technical note).
AB  - A comparison of the results obtained using the classical methods with those of
      the API 20 Strep system was carried out in identifying 24 enterococci strains
      isolated from San Simon cow's milk cheese, a traditional Spanish variety. The
      results of both identification systems coincided exactly in 9 strains (37.5% of
      the strains studied). In one strain the results obtained using the classical
      methods did not coincide with those using the API 20 Strep method. 3 strains
      (12.5%) could not be identified using the API 20 Strep system. However, 11
      strains (45%), that remained doubtful between both species E. faecalis and E.
      faecium on the basis of the classical methods, were identified using the API 20
      Strep system. The API 20 Strep system does not include some biochemical tests of
      importance in identifying of foodborne enterococci and could not identify the
      atypical strains of Enterococcus. Moreover, this system is adapted to the
      identification of enterococci of clinical origin and their database does not
      include some species common in foods. However, it could have an application in
      combination with the classical methods in order to carry out a reasonably rapid
      and reliable identification of enterococci related to cheese.

PMID- 12073819
TI  - Hyperproliferation of normally quiescent keratinocytes in non-lesional psoriatic
      skin due to high calcium concentration (an organotypic culture model).
AB  - Calcium plays an important role in the regulation of different functions of
      keratinocytes. In the present work we studied the effect of different
      extracellular calcium concentrations (0.01 mM-2.0 mM) on the proliferation and
      differentiation of human keratinocytes in normal human and non-lesional psoriatic
      skin. Using explant culture model, the proliferative and differentiated subsets
      of keratinocytes were detected by specific antibodies related to cell
      proliferation [beta-1 integrin (CD29), proliferating cell antigen (Ki67),
      proliferating cell nuclear antigen (PCNA)] and differentiation [differentiated
      cell cytokeratins (K1/K10) and differentiating cell antigen (lectin Ulex
      europaius agglutinin, UEA-1)]. After 4 days of culturing at high Ca2+ (2.0 mM) we
      observed marked hyperproliferation among the normally quiescent keratinocytes of
      non-lesional psoriatic skin. In normal uncultured and cultured skin and in
      uncultured and two-day-cultured non-lesional psoriatic skin both at normal (1.2
      mM) and at high (2.0 mM) Ca2+ concentration only one layer of basal
      CD29+/Ki67+/K1/K10-/UEA-1- cell was observed. In sections from non-lesional
      psoriatic skin cultured for 4 days in the presence of high Ca2+ (2.0 mM) this
      cell population has expanded from at least three layers above the basement
      membrane. This expanded cell population of the 4-day high Ca2+ cultured non
      lesional skin showed clear PCNA positive staining on frozen sections with the
      strongest positivity among the most basal localized cells. These data suggest
      that (i) extracellular Ca2+ concentration can influence the proliferation of
      basal ("stem") keratinocytes, (ii) the proliferative response to high Ca2+
      concentration of psoriatic non-lesional basal keratinocytes differs from that of
      normal basal keratinocytes, (iv) changes in the extracellular Ca2+ milieu might
      play a role in the induction of the hyperproliferative psoriatic lesion.

PMID- 12073821
TI  - Neonatal pneumonia caused by Trichomonas vaginalis.
AB  - The authors present two cases of newborn babies infected by Trichomonas vaginalis
      (hereafter referred to as T. vaginalis) and suffering from severe congenital
      breathing difficulties and needing artificial respiration. Microscopic
      examination of the tracheal discharge revealed characteristically moving,
      flagellated, pear-shaped unicellular organisms. Cultures on CPLM medium proved
      the presence of T. vaginalis. During pregnancy the mothers' clinical status was
      negative and both of them mentioned leukorrhoea of changing intensity. They were
      regularly involved in antenatal care. The infection caused by T. vaginalis could
      be detected in the two mothers later by culture procedures.

PMID- 12073820
TI  - Luminometric and differential scanning calorimetry (DSC) studies on heat- and
      radiation inactivation of Bacillus subtilis luxAB spores.
AB  - A bioluminescent derivative of Bacillus subtilis containing a plasmid encoding a
      luxAB fusion under control of a vegetative promoter and gives bioluminescence
      upon addition of an exogenous long-chain aldehyde has been used as test organism.
      Its spore populations have been produced and their heat- and radiation survival
      curves established. Heat-sensitization effect of pre-irradiation of spores was
      proven not only by colony counting but also with differential scanning
      calorimetry. Under a linearly programmed temperature increase, the heat
      destruction of spores surviving 2.5 kGy gamma irradiation resulted in at a few
      centigrade lower temperature than that of untreated spores. Heat denaturation
      endotherms in the DSC-thermogram of irradiated spores were shifted to lower
      temperatures as well. Comparative turbidimetric, luminometric and phase-contrast
      microscopic studies of untreated, heat-treated and irradiated spore populations
      showed that the kinetics of germination and the light emission during germination
      of radiation-inactivated spores were the same as those of untreated spores,
      revealing that the pre-formed luciferase enzyme packaged into the spores during
      sporulation remained intact after an irradiation dose causing 90% decrease in
      number of colony forming spores. Therefore, in contrast to heat-treated spores,
      the initial bioluminescence reading upon germination of irradiated spores does
      not reflect the viable count of their population.

PMID- 12073822
TI  - Plasma endotoxin level of healthy donors.
AB  - The plasma level of endotoxin was determined in 116 healthy blood donors. After a
      routine physical and laboratory investigations the endotoxin level was determined
      with Limulus amebocyte lysate assay (LAL-test) by the chromogenic kinetic method
      of Bio-Whittaker Co. (USA). Its sensitivity was 0.005-50 EU/ml. The plasma level
      of endotoxin in most of the healthy donors was less than 1 EU/ml (in the range of
      0.01-1.0 EU/ml), but always measurable. The average +/- S.D. was 0.128 +/- 0.215
      EU/ml. Because of the high standard deviation and high range of values, the data
      were distributed into two groups with the means of 0.05 +/- 0.022 EU/ml and 0.294
      +/- 0.186 EU/ml. The difference between the groups was significant (p < 0.001).
      In conclusion, endotoxin can be measured in plasma of healthy individuals.

PMID- 12073823
TI  - Stress related changes of cell surface hydrophilicity in Bacillus subtilis.
AB  - The changes of cell surface hydrophilicity in Bacillus subtilis were analyzed in
      response to oxygen-limitation, heat shock, salt stress, pH-shock, phosphate- and
      carbon-limitation. Although cell surface hydrophilicity varied during growth
      phases, an increase of surface hydrophilicity was observed under several of these
      stress conditions. An observed drop in intracellular GTP and/or ATP may be an
      element of the signal transduction pathway leading to an increase in surface
      hydrophilicity in response to environmental stresses. Attachment of cells to soil
      particles under salt stress conditions is strongly influenced by the degS/degU
      two-component system, which thereby provides a mechanism for the bacteria to
      escape from the hostile environment.

PMID- 12073824
TI  - Comparative studies on Aeromonas strains isolated from Lakes Balaton (Hungary)
      and Ferto/Neusiedlersee (Hungary).
AB  - Ecological and comparative taxonomic investigations were carried out on 49
      Aeromonas strains isolated from water samples of two moderately alkaline lakes of
      Hungary, Lake Balaton and Lake Ferto/Neusiedlersee together with 3 authentic
      strains of Aeromonas hydrophila. Five phena were created at greater than 92%
      similarity value using the UPGMA method with the Jaccard coefficient. Strains
      isolated from Lake Balaton were determined as A. hydrophila, while strains
      originated from Lake Ferto were identified as A. hydrophila and A. sobria. The
      Ferto isolates of A. hydrophila grew only at higher salt concentration (5% NaCl).
      This might be an adaptation to the higher salt contents in the water of Lake
      Ferto. However, no specific differences were detected in their behaviour against
      alkaline pH values. The wide range of their degradative enzymes indicate that
      aeromonads can play an important role in nutrient cycling.

PMID- 12073825
TI  - Effect of fluoride on cariogenic oral microorganisms (an in vitro study).
AB  - The effect of sodium fluoride and sodium monofluorophosphate at concentrations of
      1, 5, 10, 50, 100 and 1000 mg/l in phosphate buffer (pH 6.5) as well as in UHT
      milk were studied on cultures and suspensions of Streptococcus mutans,
      Lactobacillus acidophilus and Candida albicans. Using serial tenfold dilutions up
      to 10(-7) of 24-48 hour cultures, a subsequent 0, 60 and 120 min incubation
      caused no decrease in the number of CFUs. Growth kinetic studies in the Bioscreen
      biophotometer (Labsystem, Finland) revealed that sodium fluoride in different
      concentrations (from 0.875 mg/l up to 500 mg/l) influenced the growth dynamics of
      S. mutans and C. albicans: the exponential phase flattened out at the highest
      fluoride concentrations (500 mg/l) present in the growth media. The lag phase of
      C. albicans became longer. The results of these experiments indicate that sodium
      fluoride administered at higher concentrations than the usual caries preventive
      dosage made the generation time of cariogenic oral bacteria and fungi longer,
      slowing down their multiplication.

PMID- 12073826
TI  - Karyotyping of Candida albicans and Candida glabrata isolates from recurrent
      vaginal infections by pulsed-field gel electrophoresis.
AB  - In the present study, 16 women with recurrent vulvovaginal candidiasis (RVVC) due
      to Candida albicans and Candida (Torulopsis) glabrata were followed for a period
      of 4 to 12 months, and 36 vaginal isolates were evaluated by pulsed-field gel
      electrophoresis (PFGE). Eleven women were infected by C. albicans and 5 by C.
      glabrata. Three electrophoretic karyotypes of C. albicans and 3 of C. glabrata
      were identified throughout the follow-up. All patients but one was infected with
      the same karyotype of C. albicans or C. glabrata during the follow-up period. Two
      different karyotypes of C. glabrata were identified in one patient in the course
      of 12 months. The results confirmed the diversity of the karyotypes of C.
      albicans and C. glabrata causing vulvovaginitis, and demonstrated the persistence
      of colonization with the same strain over different periods of time despite
      therapy (15/16 women).

PMID- 12073827
TI  - Fluorescence in situ hybridization (FISH) in the molecular cytogenetics of
      cancer.
AB  - In this review, we discuss the developments of fluorescence in situ hybridization
      (FISH) and place them in the context of their applications in cancer research.
      These methods are not only very useful for the causal analysis of the development
      and spread of certain tumors, they are also efficient tools for tumor diagnosis.
      Although a review of all of the literature in this field is not possible here,
      many of the major contributions are summarized along with recent work from our
      laboratory. Our group contributes to the goal of functional identification of
      tumor growth antagonizing genes. FISH and molecular analyses have shown that the
      short arm of human chromosome 3 is frequently deleted in kidney, lung, breast,
      uterus, testis and ovary carcinomas. Deletion-mapping studies have outlined
      several separate deletion prone regions in different tumors, namely 3pter-p25,
      p22-p21.3, p21.1-p14 and p14-p12, which may contain putative tumor suppressor
      genes (TSGs). Candidate suppressor genes isolated from frequently deleted regions
      need to be assayed for possible tumor-antagonizing ability by functional tests.
      We have developed a functional test system, the microcell hybrid (MCH) based
      "elimination test" (Et). The Et is based on the introduction of a single human
      chromosome into tumor cells of human or murine origin, via microcell fusion. The
      MCHs were analyzed by FISH painting and PCR for the elimination or retention of
      specific human chromosome 3 (chr. 3) regions after one or several passages in
      severe combined immunedeficient (SCID) mice. We have defined a common eliminated
      region (CER) on chr. 3p21.3. CER is approximately 1 megabase (Mb) in size. We
      have covered this region with PACs (bacteriophage PI based artificial chromosome)
      and used FISH mapping for localization and ordering PACs and cosmids on the
      chromosome 3 and high-resolution free chromatin/DNA fiber FISH to orient the PAC
      contig, to measure the lengths of PACs, and to establish their order. Activation
      of cellular oncogene by chromosomal tanslocation, which brings an oncogene under
      the influence of a highly active chromosome region, appears to play a pivotal
      role in the genesis of certain hematopoetic and lymphoid tumors. We have detected
      specific chromosomal translocations by FISH painting in mouse plamacytoma (MPC),
      human Burkitt lymphoma (BL) other B-cell derived tumors. We have showed in a
      murine sarcoma derived line (SEWA) that FISH can be also be used for detection of
      amplified oncogene (c-myc) and the linked locus (pvt-1). We have also applied the
      FISH technique for visualization of integrated and episomal Epstein-Barr virus
      (EBV) genomes and EBV transcripts in EBV-carrying B-cell derived human cell
      lines.

PMID- 12073828
TI  - Molecular typing of Listeria monocytogenes.

PMID- 12073829
TI  - Seroprevalence of antibodies to hepatitis A and E viruses in pediatric age groups
      in Turkey.
AB  - Hepatitis A and hepatitis E are enteric transmitted viral diseases occurring in
      epidemic and sporadic forms especially in developing countries. Previous studies
      in Turkey showed that most residents are infected with HAV by the second decade
      of life. Since HEV is generally transmitted by the same route as HAV we conducted
      a community-based seroprevalence study for HAV and HEV infection in Ahatli area
      in Antalya, Turkey where socioeconomic conditions are low. Anti-HAV total
      immunoglobulin was tested by using a microparticle EIA (Axsym-Abbott Lab). Anti
      HEV IgG was assayed by a micro ELISA method (Genelabs-Singapore). Of the 338 sera
      tested, 112 (33.1%) were positive for anti-HAV total antibody. Anti-HEV IgG was
      detected in three (0.89%) of the serum samples. Seropositivity rates of HAV in
      preschool and school children were 19.9% and 43.9% respectively (p < 0.001). No
      antibody to HEV was detected in preschool children, while the prevalence of anti
      HEV IgG was 1.6% in children attending school. Our data showed that
      seroprevalence of anti-HAV is high among children samples but HEV infection
      appears to be relatively rare in pediatric age groups.

PMID- 12073830
TI  - The immunosuppressive effect of Fusarium mycotoxin as a function of HLA antigens.
AB  - We examined the blastogenic response to phytohaemaglutinin (PHA) in HLA-B8, DR3
      positive and negative subjects in the presence or absence of the
      immunosuppressive Fusarium mycotoxin. HLA-B8, DR3 haplotype was associated with a
      depression of the response to mitogen in the absence of the mycotoxin, whereas in
      the presence of deoxynivalenol we could not detect significant differences among
      individuals either possessing or lacking this haplotype.

PMID- 12073831
TI  - [Principles of surgical treatment of tuberculous empyema].

PMID- 12073832
TI  - [Intensive therapy of patients with pulmonary tuberculosis].
AB  - The experience of intensive therapy of 23 patients with infiltrative pulmonary
      tuberculosis is presented. The complex approach that permits to solve the problem
      of resistant Mycobacterium tuberculosis and chemotherapy poor tolerance is
      substantiated.

PMID- 12073833
TI  - [Drug resistant pulmonary tuberculosis: problems of diagnosis and treatment in
      hospital conditions].
AB  - The number of drug-resistant forms of pulmonary tuberculosis increases every
      year. The diagnosis of drug resistance of Mycobacterium tuberculosis (MBT) is
      rather difficult, up-to-date (molecular-and-genetic) methods should be applied.
      236 patients with active pulmonary tuberculosis and massive bacterial excretion
      were investigated in Central Military Clinical Tubercular Hospital. 97 (41.1%) of
      them had drug resistant MBT (1 drug resistance was revealed in 15.5%, two drugs-
      in 28.8% and three and more drugs--in 55.7%). Rifampicin resistance was the
      highest one (40%). The authors propose the complex schemes of drug resistance
      prophylaxis and decrease in the patients with pulmonary tuberculosis.

PMID- 12073834
TI  - [Optimal treatment periods of first-revealed localized form of pulmonary
      tuberculosis].

PMID- 12073835
TI  - [Long-term treatment results in servicemen with nephronophthisis].

PMID- 12073836
TI  - [Sarcoidosis in servicemen. Problems of detection and dynamic dispensary check
      up].

PMID- 12073837
TI  - [Diagnosis and principles of complex therapy of sarcoidosis].
AB  - The diagnosis and therapy of 87 patients with sarcoidosis admitted to the Central
      Military Clinical Tubercular Hospital were analyzed. The diagnosis was based on
      the data of clinicoroentgenologic investigation and histologic examination of the
      specimen taken from the affected tissue. The differential diagnosis with
      tuberculosis is obligatory. The complex therapy includes corticosteroids,
      antioxydants, phytotherapy, physiotherapeutic methods and in some cases
      plasmapheresis.

PMID- 12073838
TI  - [Ambroxol in etiotropic chemotherapy of pulmonary tuberculosis].

PMID- 12073840
TI  - [Physiotherapy in the treatment of pulmonary tuberculosis].
AB  - On the base of considerable number of clinical observations the results of
      application of physiotherapeutic methods in the complex therapy of the patients
      with pulmonary tuberculosis are presented. Indications and contraindications for
      physiotherapeutic methods are substantiated.

PMID- 12073839
TI  - [Pathology of digestive organs in tuberculosis patients].

PMID- 12073841
TI  - [System of centralized control of tuberculosis in the armed forces of the Russian
      Federation].
AB  - Tuberculosis belongs to the group of controllable diseases. Epidemic control
      should characterize not only the effectiveness of each of anti-tubercular
      measures individually but the result of their complex conduction. The specialists
      of Central Military Clinical Tubercular Hospital have developed the main
      principles of All-Army system of tuberculosis centralized control (monitoring),
      the technology of information collection, storage and analysis. It consists of
      three levels: the territorial (garrison), the specific (district, naval) and the
      all-army. The All-Army register of tubercular patients (servicemen under the
      contract and RF MD pensioners) is complied.

PMID- 12073842
TI  - [State of cardiorespiratory system and general hemodynamics in healthy persons].

PMID- 12073843
TI  - [Medication-induced hepatic lesions in patients with pulmonary tuberculosis].

PMID- 12073844
TI  - [Perspectives on the treatment of organic mental disorders by the use of
      nootropic agents].

PMID- 12073846
TI  - [Repeat surgical intervention on mitral valve for restenosis].

PMID- 12073845
TI  - [Use of rispolept for psychotic symptoms in elderly patients with vascular
      psychoorganic syndrome].

PMID- 12073847
TI  - [Problem of premorbid cognitive function after brain concussion].

PMID- 12073849
TI  - [Use of the "Physomed" belt in the treatment of kidney stones].

PMID- 12073848
TI  - [Immunotherapy of genital herpes by multicomponent vaccine VP-4].

PMID- 12073850
TI  - [Work experience of a garrison hospital deployed in prefabricated modules in a
      war zone].

PMID- 12073851
TI  - [50th anniversary of the Central Military Clinical Tuberculosis Hospital].

PMID- 12073852
TI  - [The Medical Service of the Siberian Military District in World War II].

PMID- 12073853
TI  - Pharmacists, technician found liable for millions in medication error.

PMID- 12073854
TI  - Prescribing authority for VA pharmacists to continue as is--for now.

PMID- 12073855
TI  - Applying human factors in improving medication-use safety.
AB  - The application of human factors (HF) in improving medication-use safety is
      described. HF has been shown to improve the performance of people working within
      systems, especially in environments that rely on technology. HF applications in
      health care center around automation design and highly controlled environments,
      such as the operating room. To explore the application of HF to the highly
      variable process of medication use, an interactive conference was planned in
      which the fundamental principles of HF were presented to an audience of health
      care professionals. Workshops were organized to teach participants how to
      integrate HF into their practices, covering such areas as the basic principles of
      HF, applications of HF for improving medication-use safety, and strategic
      resources for organizations wishing to apply HF to their systems to improve
      medication-use safety. This report summarizes the highlights of this conference.
      By applying HF to existing and future systems, health care professionals can
      improve medication-use safety by reducing the occurrence of human errors. The
      culture, variability, complexity, and hierarchical nature of health care make the
      application of HF more difficult than in other environments in which some or all
      of these issues are less prevalent. Most health care providers are not educated
      in the discipline of HF, so it is important to increase their sensitivity to the
      limits of human performance and their understanding of the need to make system
      changes to accommodate these limits. Experts in this field can help health care
      professionals identify and improve complex, high-risk procedures and
      technologies. The potential benefit of hiring or consulting these experts
      requires organizations to make a commitment to change procedures, equipment, and
      their culture to improve patient safety.

PMID- 12073856
TI  - Role of poison control centers in disaster response planning.

PMID- 12073857
TI  - Health-system pharmacy: new practice framework and leadership model.

PMID- 12073858
TI  - Managing hyperlipidemia: current and future roles of HMG-CoA reductase
      inhibitors.
AB  - The current and future roles of statins as antilipemic agents for the prevention
      and management of coronary artery disease (CAD) are reviewed. Therapy with
      hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) substantially
      reduces total cholesterol and low-density-lipoprotein (LDL) cholesterol
      concentrations. Large clinical trials have documented the efficacy of statin
      therapy for both primary and secondary prevention of CAD. Nevertheless, many
      eligible patients are either untreated or inadequately treated with these agents.
      In one study, 61% of patients with documented CAD were not treated with a lipid
      lowering agent. Large percentages of high-risk patients receiving such agents are
      not meeting cholesterol goals set by the National Cholesterol Education Program
      (NCEP). Populations at increased risk for coronary events include patients with
      diabetes, women, the elderly, and patients with established CAD. Comparative
      studies have not shown any one agent as clearly superior to the others. Future
      possibilities for statin use include early treatment of hypercholesterolemia and
      acute coronary syndromes consistent with guidelines established by NCEP. Many
      clinicians now believe that an aggressive approach to lowering LDL cholesterol
      may yield even greater reductions in coronary events. Treatment may reduce the
      risk of recurrent ischemic events when initiated within 96 hours of
      hospitalization for acute myocardial infarction or unstable angina and continued
      for up to four months. Another use may be the management of atherosclerotic
      cerebrovascular disease. Closer attention to potential adverse effects will be
      necessary before any expansion in statin use. Statins are highly effective for
      improving cardiovascular outcomes in high-risk patients but are frequently
      underused. Pharmacists can help extend the benefits of statins to more patients.

PMID- 12073859
TI  - Evaluating the accuracy of technicians and pharmacists in checking unit dose
      medication cassettes.
AB  - The accuracy rates of board-registered pharmacy technicians and pharmacists in
      checking unit dose medication cassettes in the inpatient setting at two separate
      institutions were examined. Cedars-Sinai Medical Center and Long Beach Memorial
      Medical Center, both in Los Angeles county, petitioned the California State Board
      of Pharmacy to approve a waiver of the California Code of Regulations to conduct
      an experimental program to compare the accuracy of unit dose medication cassettes
      checked by pharmacists with that of cassettes checked by trained, certified
      pharmacy technicians. The study consisted of three parts: assessing pharmacist
      baseline checking accuracy (Phase I), developing a technician-training program
      and certifying technicians who completed the didactic and practical training
      (Phase II), and evaluating the accuracy of certified technicians checking unit
      dose medication cassettes as a daily function (Phase III). Twenty-nine
      pharmacists and 41 technicians (3 of whom were pharmacy interns) participated in
      the study. Of the technicians, all 41 successfully completed the didactic and
      practical training, 39 successfully completed the audits and became certified
      checkers, and 2 (including 1 of the interns) did not complete the certification
      audits because they were reassigned to another work area or had resigned. In
      Phase II, the observed accuracy rate and its lower confidence limit exceeded the
      predetermined minimum requirement of 99.8% for a certified checker. The mean
      accuracy rates for technicians were identical at the two institutions (p = 1.0).
      The difference in mean accuracy rates between pharmacists (99.52%; 95% confidence
      interval [CI] 99.44-99.58%) and technicians, (99.89%; 95% CI 99.87-99.90%) was
      significant (p < 0.0001). Inpatient technicians who had been trained and
      certified in a closely supervised program that incorporated quality assurance
      mechanisms could safely and accurately check unit dose medication cassettes
      filled by other technicians.

PMID- 12073860
TI  - 2001 anthrax crisis in Washington, D.C.: clinic for persons exposed to
      contaminated mail.
AB  - An anthrax prophylaxis clinic is described. In October 2001, four workers from
      the U.S. Postal Service's Brentwood facility in Washington, D.C., were
      hospitalized with inhalational anthrax; many others may have been exposed to
      anthrax spores. U.S. Public Health Service (USPHS) teams were deployed to
      establish an anthrax prophylaxis clinic that would provide education and
      medication to workers and people who visited the mail facility. The temporary
      clinic was set up at D.C. General Hospital and was staffed primarily by health
      care professionals from USPHS. The protocol at the clinic involved three major
      phases. Phase 1 consisted of gathering information from the patient and
      distributing educational materials. Phase 2 involved presentations by a physician
      and a pharmacist concerning anthrax, followed by a question-and-answer session.
      In phase 3, a pharmacist selected the most appropriate prophylactic agent,
      dispensed the medication, counseled the patient, and referred patients with flu
      like symptoms or skin lesions to a physician. Two floor plans were used to
      maximize the number of patients seen per hour without jeopardizing patient care.
      The clinic operated 14 hours a day for 14 days. The 136-member health care team
      included 52 pharmacists, and medication was dispensed to more than 18,000
      patients. The clinic may serve as a model for pharmacists and other professionals
      in designing and implementing disaster plans. A multidisciplinary team
      established and operated a clinic to treat persons who may have been exposed to
      anthrax through contaminated mail.

PMID- 12073861
TI  - 2001 anthrax crisis in Washington, D.C.: pharmacists' role in screening patients
      and selecting prophylaxis.
AB  - Pharmacists' development and use of a worksheet facilitating their rapid
      selection of patient-appropriate prophylactic antimicrobials in an anthrax clinic
      is described. A clinic housed at D.C. General Hospital, in Washington, D.C.,
      treated most of the people--many of them postal workers--who may have been
      exposed to anthrax in that city during the 2001 anthrax crisis. A form was needed
      to assist pharmacists in the rapid selection of prophylactic antimicrobials and
      in patient education and counseling. A team of pharmacists collaborated on the
      development of a form tailored to the clinical and logistical needs of the
      operation. The questions on the form were based largely on the two antianthrax
      agents most likely to be used, ciprofloxacin and doxycycline, and were designed
      to identify the circumstances that would most frequently require a medication
      change or a modification of patient education. Yes-or-no check boxes allowed
      pertinent data to be captured most efficiently. A positive response to any
      question triggered a personal interview and assessment by a pharmacist. A
      treatment algorithm was also developed to ensure consistent pharmacist selection
      of agents in the face of potentially changing policies and staff. The worksheet
      questions sought to establish treatment objectives, document allergies and
      concomitant therapies, and identify patients who were pregnant or lactating.
      Pharmacists developed a patient-screening worksheet that helped determine their
      choice of treatment for people who may have been exposed to anthrax in
      Washington, D.C., during the 2001 anthrax crisis.

PMID- 12073862
TI  - Implementing and evaluating a pharmacy consult service within a family medicine
      residency program.

PMID- 12073863
TI  - Student conduct at the personnel placement service.

PMID- 12073864
TI  - Possible interaction between gatifloxacin and warfarin.

PMID- 12073865
TI  - Emergency contraception services.

PMID- 12073866
TI  - Trends in utilization of coronary artery bypass surgery and associated outcomes:
      Alberta, Manitoba, and Nova Scotia.
AB  - The primary objective of this study was to examine trends in rates and outcomes
      of coronary artery bypass graft (CABG) surgery across the 3 Canadian provinces of
      Alberta, Manitoba, and Nova Scotia, during fiscal years 1991-1995. Annual age
      standardized CABG surgery rates were calculated by sex for each province.
      Province-specific average length of stay (ALOS) and postsurgical complication
      rates were calculated using ICD-9 codes. Rates of CABG were higher among men
      compared with women in all 3 provinces. Whereas ALOS, complications rates, and
      mortality rates decreased in all provinces over the study period, there was
      considerable variation in province-specific rates.

PMID- 12073867
TI  - Risk-adjustment of cesarean delivery rates: a practical method for use in quality
      improvement.
AB  - Risk-adjustment of cesarean birthrates has been hampered by inadequacies in the
      existing secondary data sources or by the need for extensive chart review. This
      study presents an efficient risk-adjustment model for cesarean birth, based on
      easily retrievable ICD-9 codes and clinical risk factors least influenced by
      physician practice style. Data are presented for mothers undergoing 7322
      deliveries from 1997-1998 at a large academic medical center with a cesarean
      birth rate of 15.9%. Multiple logistic regression was used to predict the
      likelihood of cesarean delivery controlled for maternal age, 10 risk factors
      identified through ICD-9 coding, and 3 additional clinical variables
      (nulliparity, birth weight, and gestational age) derived from a perinatal (birth
      certificate) database. All risk factors were significant predictors of cesarean
      birth, producing an area under the receiver-operating characteristic curve of
      0.86 and a 60-fold increase in cesarean delivery from highest to lowest deciles
      of predicted risk. This methodology can be used widely for quality improvement
      without the need for extensive chart review.

PMID- 12073868
TI  - Medical malpractice and quality: an interconnected problem.

PMID- 12073869
TI  - Commentary: point-counterpoint--the National Health Care Quality Report.

PMID- 12073870
TI  - Quality assurance and risk management in on-line medical discussion groups.
AB  - There are thousands of sites on the Internet and World Wide Web where health care
      professionals and lay people interact to share medical information and health
      concerns. The majority of these sites do not have procedures in place to assess
      the quality of the information supplied by the providers or lay people, nor do
      they have any formal risk management policies to respond to posted material that
      may reveal a potential risk situation. This paper describes the quality assurance
      and risk management procedures that have been developed for KP Online--the
      website for members of the Kaiser Foundation Health Plan, Inc--and shares some
      preliminary findings based on these procedures.

PMID- 12073872
TI  - Growing through occupation: courage to move forward.

PMID- 12073871
TI  - Benchmarking implementation of a computerized system for long-term care.
AB  - The purpose of this study was to apply a benchmarking methodology to identify the
      most effective approaches used by long-term care facilities in implementing new
      computerized resident assessment instrument/minimum data set (RAI/MDS) systems
      and to develop implementation protocols based on these "best practices." Site
      visits were conducted with 3 long-term care facilities, selected on the basis of
      a national search. Facility directors, directors of nursing, information system
      managers, and frontline staff at each facility were targeted, and questionnaires
      were developed for each to assess factors viewed as important to successful
      implementation. A convergence was found in recommended action steps reported
      across sites to facilitate introduction and implementation of new RAI/MDS
      software. An example of how benchmarking results were used to develop an
      implementation plan is provided. Benchmarking provided a useful methodology for
      identifying best practices to guide implementation planing for adoption of a new
      computerized RAI/MDS system in the current trial. The benchmarking steps
      described are replicable and can be used to guide implementation of other new
      systems in the nursing home setting.

PMID- 12073873
TI  - Negotiation-centred versus client-centred: which approach should be used?
AB  - For nearly 20 years, Canadian occupational therapists have attached great
      importance to the client-centred approach within their practice. Professionals
      have agreed to define this approach through a philosophy built around the
      concepts of respect, power and partnership. But no reported work has really
      clarified what is meant by these three fundamental concepts. This article
      attempts to define the concepts of respect and power in the therapist-client
      relationship through a review of occupational therapy and related health and
      social sciences literature. It raises the question: "In the professional-client
      relationship, should the power reside with the client or is a more balanced
      approach needed?" This paper also proposes using the term negotiation instead of
      partnership, since negotiation seems to offer more applications for occupational
      therapy practice. The objective of the authors who advocate for greater
      negotiation between client and therapist is to stimulate analysis.

PMID- 12073874
TI  - The impact of reimbursement systems on occupational therapy practice in Canada
      and the United States of America.
AB  - Different funding and cost-control mechanisms in Canada and the United States of
      America (USA) have a powerful influence on occupational therapy practice in each
      country. Canada's public health insurance system emphasizes access to health care
      services based on medical need. Costs are controlled at the provincial government
      level by limiting the capacity of facilities and personnel. Occupational
      therapists in publicly-funded settings have considerable professional autonomy to
      use occupational therapy theoretical models and to be client-centred. The
      measurement of outcomes is not always required and the interventions of
      individual occupational therapists are infrequently scrutinized. The USA has no
      universal, publicly-funded, comprehensive health insurance. Health care policies
      are driven by financial priorities and cost control occurs at the service
      delivery level. Insurance companies define the scope of occupational therapy
      practice by identifying what services they will pay for and they scrutinize
      occupational therapy interventions. The emphasis on effectiveness and efficiency
      leads to critical examination of interventions by therapists. Canadian
      occupational therapists can learn much from their colleagues in the USA in this
      area.

PMID- 12073875
TI  - Reflections on.... Occupational therapy and assertive community treatment.
AB  - Occupational therapists can play a valuable role on Assertive Community Treatment
      Teams (ACT). ACT is a widely disseminated, community based model of service
      delivery for individuals with severe psychiatric disabilities and high support
      needs. This paper discusses the generalist and specialist functions of
      occupational therapists within ACT. It is argued that occupational therapy
      addresses the occupational health and well being of ACT clients by intervening at
      three levels: the individual, the program and the community. This occupational
      focus is consistent with the ACT goal of enhancing community adjustment and
      quality of life. The paper concludes with a discussion of the opportunities and
      the constraints that face occupational therapists working within ACT.

PMID- 12073876
TI  - An application of the Occupation Competence Model to organizing factors
      associated with return to work.
AB  - The variations in return to work outcomes for ill or injured persons experiencing
      health leaves are complex. However, it is important to comprehend these
      variations in order to develop evidenced-based practice in work rehabilitation.
      Currently, a plethora of studies exist in the literature that have attempted to
      explain the variations in work outcomes. A 20-year review of the literature on
      work outcomes has revealed several limitations in using this knowledge in
      occupational therapy. The study of return to work outcomes is, for the most part,
      atheoretical and the knowledge base is fragmented and disorganized. In addition,
      the literature does not reflect a consistent understanding of the
      multidimensional nature of either work disability or the facilitators for return
      to work. In this paper, the Occupational Competence Model is presented as a
      framework for filling this gap. This model is used here to organize and
      synthesize the factors previously studied on work outcomes to foster an
      understanding of this literature from an occupational therapy perspective and the
      future study of work outcomes and work rehabilitation.

PMID- 12073877
TI  - Will students be prepared? Current status of gerontological content in entry
      level occupational therapy programs in Canada.
AB  - By the year 2020, 20% of the Canadian population is expected to be over the age
      of 65 (Statistics Canada, 1997). It is important that future clinicians are
      prepared to meet the increased demand for occupational therapy services by older
      adults. The purpose of this study was to examine the present status of
      gerontological content within Canadian occupational therapy programs. A survey
      was sent out to all twelve entry-level occupational therapy university programs
      in Canada via electronic mail. This survey asked questions about the programs'
      focus on gerontological content within their coursework and clinical fieldwork.
      All ten responding programs indicated that they had gerontological content within
      their curricula. However, the amount and content varied throughout the programs.

PMID- 12073878
TI  - Literacy of children with physical disabilities: a literature review.
AB  - The ability to read and write can influence an individual's educational,
      communication, and vocational opportunities. Occupational therapists can assist
      children with physical disabilities to achieve literacy skills. By setting
      priorities and goals for each child, in conjunction with their parent(s),
      opportunities can be provided and technologies utilized to access literacy
      material and enhance the child's abilities to read and write. This extensive
      literature review provides clinicians with information on the factors that
      influence the development of literacy for children with physical disabilities.
      The expectations and priorities of parent(s) are critical determinants of whether
      opportunities will be provided for the child to learn to read and write. This
      article concludes with recommendations and strategies for the use of technology
      to help develop literacy skills, and future research questions for
      considerations.

PMID- 12073879
TI  - Carbonaceous components in atmospheric aerosol: measurement procedures and
      characterization.
AB  - Carbonaceous material in the particulate matter was measured in Rome urban area.
      The carbonaceous material constitutes a significant component of total aerosol
      mass (30-40%) and it is composed by two main fractions, elemental carbon (EC) and
      organic carbon (OC). EC is essentially a primary pollutant emitted directly from
      incomplete combustion processes whereas OC has both primary and secondary origin.
      A chemical OC investigation has been carried out in order to determine the
      nalkanes, the n-alkanoic acids, the polycyclic aromatic hydrocarbons (PAHs) and
      nitro-PAHs by means an HRGC-MS procedure. A different seasonal distribution of
      these compound classes attributed to photochemical radical activity (n-alkanes
      and PAH decrease in spring- and summertime) and to biogenic plant emission (n
      alkanoic acid increase in summertime) has been evidenced.

PMID- 12073880
TI  - Free and total amino acid composition in blue-green algae.
AB  - A simple, accurate and reproducible analytical method is described for the
      extraction and the simultaneous determination of 18 amino acids in different for
      geographical origin Spirulina alga samples using phenylisothiocianate as
      derivatizating agent in natural feed. The best experimental hydrolysis conditions
      have been studied varying the temperature, the time and the hydrolyzing reagent.
      The separation and the quantitative analysis of the by-products have been carried
      out by HPLC analysis and UV detection. An amino acid pattern is compared with
      that proposed by the Food Agriculture Organization (FAO) for an ideal protein and
      with those of some traditional feed.

PMID- 12073881
TI  - Air monitoring of volatile aromatic compounds by means of long-term exposure
      diffusive samplers.
AB  - Results obtained by using "Analyst", a long-term diffusive sampler, in some
      monitoring campaigns, performed for the determination of benzene and the volatile
      aromatic pollutants, in five cities of the Italian Umbria Region and at the city
      of Forli, are presented and discussed. First results of an inter comparison
      between the "Analyst" and "radial-type" diffusive samplers, carried out by the
      Regional Agency for the Ambient Protection (ARPA) of Forli, point out substantial
      advantages with the long-time sampling devices.

PMID- 12073882
TI  - Analysis of limette and bergamot distilled essential oils by HPLC.
AB  - This work examines the distilled essential oils of limette and bergamot in order
      to assess the presence of low volatile substances such as coumarins (bergapten)
      which, being toxic, must be eliminated before using these oils in the food
      industry. The quantitative determination of coumarins was carried out by
      spectrofluorimetric detection. The substances present in the chromatograms,
      obtained by HPLC with UV detection at 254 nm, were then identified. Moreover, a
      new coumarin that is present in small quantities was identified using HPLC-MS.

PMID- 12073883
TI  - Eptastigmine, nicotinamide and nicotinic acid determination using an inhibition
      enzyme sensor; application to pharmaceutical analysis.
AB  - An enzyme inhibition biosensor, developed in our laboratory and previously used
      for the analysis of compounds with anticholinesterase activity (e.g.
      physostigmine, neostigmine, pyridostigmine nicotine and organophosphorus
      compounds) has now been tested for the analysis of another recently synthesized
      cholinesterase inhibitor, i.e. eptastigmine. In addition nicotinic acid and
      nicotinamide, although displaying weaker inhibition properties, were also tested
      in pharmaceutical products using the same inhibition enzyme sensor. The biosensor
      consisted of a hydrogen peroxide amperometric electrode coupled to a
      functionalised nylon membrane chemically bonding both the enzymes
      butyrylcholinesterase and choline oxidase; a butyrylcholine standard solution in
      glycine buffer acted as substrate. The response of the system to all the
      inhibitors considered was characterised completely and the analysis of several
      pharmaceutical formulations containing nicotinamide or nicotinic acid was also
      performed.

PMID- 12073885
TI  - Chemical and radiochemical characterization of depleted uranium (DU) in Kosovo
      soils.
AB  - As is well known ammunitions containing depleted uranium (DU) were used by NATO
      during the Balkan war. The paper deals with the determination of uranium alpha
      emitting radiosotopes in Kosovo soils by chemical separation and alpha
      spectrometry. The samples were collected by CISAM (Centro Interforze Studi ed
      Applicazioni Militari, S. Piero a Grado, Livorno) in the period November 1999
      April 2000. The DU distribution in soil appeared very disomogeneous; the isotope
      weight percentages for U-238, U-235 and U-234 resulted 99.76, 0.24 and 7.24.10(
      4) respectively; consequently the activity distribution was 86.42%, 1.31%, 11.63%
      and the isotope ratios were 1.52.10(-2) and 0.134 for U-235/U-238 and U-234/U-238
      showing clearly the presence of DU. A small peak at 4.49 MeV (U-236) in the alpha
      spectrum indicated that the used DU was the by-product of exhausted uranium
      reprocessing. In order to determine the chemical and physiological solubility of
      uranium a fractionation study was carried out by using the Tessier method: 55% of
      uranium showed a fair solubility, but 45% was solubilized only by 8 M HNO3.

PMID- 12073884
TI  - Characterization of nutraceuticals and functional foods by innovative HPLC
      methods.
AB  - In recent years there is a growing interest in food and food ingredient which may
      provide health benefits. Food as well as food ingredients containing health
      preserving components, are not considered conventional food, but can be defined
      as functional food. To characterise such foods, as well as nutraceuticals
      specific, high sensitive and reproducible analytical methodologies are needed. In
      light of this importance we set out to develop innovative HPLC methods employing
      reversed phase narrow bore column and high-performance anion-exchange
      chromatographic methods coupled with pulsed amperometric detection (HPAEC-PAD),
      which are specific for carbohydrate analysis. The developed methods were applied
      for the separation and quantification of citrus flavonoids and to characterize
      fructooligosaccharide (FOS) and fructans added to functional foods and
      nutraceuticals.

PMID- 12073886
TI  - A calibration curve at 2000 meters (A.S.L.): alpine valleys as field laboratories
      for teaching environmental monitoring to undergraduate students.
AB  - High-altitude alpine valleys may be considered as ideal field laboratories for
      the interdisciplinary teaching of Environmental Sciences to undergraduate
      students in a Laurea degree, since different typologies of sampling sites
      (rivers, lakes, glaciers) may be found within walking distance, and students are
      encouraged to develop cooperative learning activities. Scientific data have been
      collected by 1st year students at the University of Insubria in Como during a
      teaching program in Ventina Valley and Caronno Valley near Sondrio (Italy).
      Analytical and geochemical results will be presented and discussed on the basis
      of organic deposition and water-rock interactions.

PMID- 12073887
TI  - A study on the separation of synthetic pyrethroid stereoisomers by HPLC.
AB  - Enantiomer separation of synthetic pyrethroids was carried out on different
      chiral HPLC columns. In particular, the study provided useful information on the
      direct resolution of pyrethroids with and without alpha-ciano groups. The study
      indicated that polymeric chiral stationary phases based on cellulose derivatives
      are the most appropriate for the stereoisomer separation of cis-Biphenthrin,
      Resmethrin and (1R)-Phenothrin, whereas multiple-interaction CSPs, like (S)-1
      (alpha-naphthyl)-ethylamine/(S)-tert-leucine, are more selective for Cyfluthrin.

PMID- 12073888
TI  - Disposable electrochemical immunosensor for environmental applications.
AB  - An Immunosensor for the detection of polychlorinated biphenyls (PCB) has been
      developed, using carbon-based screen-printed electrodes as solid-phase and signal
      transducers. The immunosensor realised is based on a direct competitive
      immunoassay scheme, in which the antibody against PCB was directly immobilised
      onto the carbon surface of the screen-printed electrode. Competition between the
      PCBs present in the sample and a fixed concentration of an enzyme-labelled
      congener was realised and evaluated by electrochemical detection. The
      immunosensor developed was tested on Arochlor mixtures (1242 and 1248), and was
      applied in environmental and food analysis by testing some real samples (from
      animal tissues and marine sediments). Results obtained demonstrate the ability of
      this device to detect PCBs in complex matrices.

PMID- 12073889
TI  - Spatial and temporal distribution of inorganic species in water and sediments of
      the Tronto River ecosystem.
AB  - Analytical results are reported for the determination of inorganic species in
      water and sediments sampled in the Tronto river ecosystem. The species determined
      are Cd, Co, Cr, Cu, Fe, Mn, Ni, Zn, Hg, F, NO3-, SO4-, Na, K, Ca, Mg, NH4+ in
      integrated water, and Cd, Co, Cr, Cu, Fe, Mn, Ni, Zn, Hg in sediments. For all
      the elements, in addition to detection limits, precision and accuracy are given:
      the former, expressed as relative standard deviation (Sr), and the latter,
      expressed as relative error (e), were good, being in all cases lower than 5%.

PMID- 12073890
TI  - Measurements of chlorofluorocarbons and their replacement compounds at Monte
      Cimone: results obtained after eighteen months of observations.
AB  - Chlorofluorocarbons and their substitutes are anthropogenic compounds strongly
      involved in global change phenomena. Therefore, their atmospheric mixing-ratios
      are monitored on a worldwide scale. In order to evaluate source strength of these
      compounds in Southern Europe, in 1999 a research activity, monitoring these
      compounds in the atmosphere of the Monte Cimone (MO, Italy) was started. Air
      samples, collected on a weekly base, were analyzed using a GC-MS methodology
      recently devised by our group. The reported results, obtained after eighteen
      months of observation, are relative to four fully halogenated halocarbons and
      four hydrogenated halocarbons.

PMID- 12073891
TI  - Determination of benzimidazole anthelmintics in animal-derived biological
      matrices.
AB  - This paper describes an easy multiresidue procedure for the determination of 8
      benzimidazole anthelmintics (Albendazole, Albendazole sulphone, Albendazole
      sulphoxide, Ox-bendazole, Ossibendazole, p-OH-Fenbendazole, Fenbendazole,
      Flubendazole) in foodstuffs of animal origin for human consumption. According to
      the proposed procedure, 10 g of homogenised sample were extracted with
      acetonitrile in ultrasonic bath, the organic layer was evaporated to dryness and
      the residue dissolved in HCl 0.005 M. After an initial washing with hexane to
      remove fats, the aqueous layer was purified on SPE C2 column and the analytes
      were eluted with methanol, evaporated to dryness and reconstituted with phosphate
      buffer/acetonitrile (50/50). The solution obtained was analysed by HPLC with
      diode array detector (DAD); this detector provides useful information about the
      peaks present in routine samples, because it gains not only retention times of
      analytes, as well as their UV-spectra. Benzthiazuron was used as internal
      standard and the method was validated in the range 10-100 ppb, as requested by
      the imposed limits. The mean recoveries in spiked samples ranged between 70% and
      95%, for 10 and 100 ppb respectively. The developed method resulted sensitive,
      simple and fast. It is particularly suitable for laboratories that execute
      screening analysis on a great number of samples, observing the EC regulations
      that establish the benzimidazole Maximum Residue Limits (MRLs) in food.

PMID- 12073892
TI  - Size characterization of barley starch granules by gravitational field-flow
      fractionation: a rapid, low-cost method to assess the brewing capability of
      different strains.
AB  - Cereal starch occurs as two types of micrometer-sized granules, large and small.
      Large starch granules are more susceptible to enzymatic hydrolysis. When cereal
      starch is used for fermentation processes, as in brewing of barley malt, the
      barley strains with the highest content of large starch granules should be
      preferred. Gravitational field-flow fractionation (GFFF) is a separation method
      able to fractionate starch samples at low cost and short analysis time. In this
      work, the search for the best GFFF conditions for the analytical separation of
      barley starch within an inter-laboratory approach is presented. For different
      barley strains cultivated under monitored conditions the size distributions of
      starch granules is here quickly monitored and characterized by GFFF. As a
      consequence, dimensional characterization of barley starch can allow for the
      selection of the most suitable strains with the lowest content of non-degradable
      starch.

PMID- 12073893
TI  - Lipid content and fatty acid composition in lemon wax.
AB  - Lipids were extracted from lemon wax and fractionated into four classes on a
      silicic acid glass packed column by thin-layer chromatography (TLC). The free
      fatty acids, the fatty acid composition and the amount of each separated lipids
      were determined by capillary column gas chromatography (GC). Total lipids (TL)
      were 60 mg per 100 g raw weight and the ratio of nonpolar lipids (NPLs):
      glycolipids (GLs): phospholipids (PLs) was about 47:2:2. The main free fatty
      acids in lemon wax were hexadecanoic acid, cis-9-octadecenoic acid and cis,cis
      9,12-octadecadienoic acid, while in the lipid fractions the main fatty acids were
      hexadecanoic acid in all the fractions, cis-cis-9,12-octadecadienoic and decanoic
      acids in triglyceride (TG) fraction, dodecanoic and cis-9-octadecenoic acids in
      diglyceride (DG) fraction and tetradecanoic, octadecanoic and cis-9-octadecenoic
      acids in GL and PL fractions. The ratio of unsaturated to saturated fatty acids
      showed a remarkable difference among these four lipid fractions. In PL and GL
      fractions this ratio was similar, 47.7% and 47.1% respectively, and in TG
      fraction it was 42.4% while in DG fraction this value was 23.5%.

PMID- 12073894
TI  - Integral toxicity test of sea waters by an algal biosensor.
AB  - An integral toxicity test, based on an algal biosensor and suitable to be used in
      sea water, is presented. The biosensor was designed and built by coupling a Clark
      oxygen electrode as transducer and the marine alga Spirulina subsalsa as
      biological mediator; it constitutes the "core" in a lab-scale prototype of a flow
      apparatus suitable to continuously monitor, in sea water, the photosynthetic
      activity of the alga and, from its variation, the marine pollution from the
      toxicological point of view. Inorganic pollutants (heavy metals) were tested in
      previous researches while organic ones (chlorophenols, pesticides and
      surfactants) are the object of the present paper.

PMID- 12073895
TI  - Trace determination of Ni and Cd in standard matrixes for ISO textile leaching
      tests.

PMID- 12073896
TI  - Infanticide up close: reflecting on Andrea Yates.

PMID- 12073897
TI  - Barriers to student preventive practices during preclinical preceptorship.

PMID- 12073898
TI  - Muscling up.

PMID- 12073899
TI  - Resuscitate or not?

PMID- 12073900
TI  - Persistent pertussis.

PMID- 12073901
TI  - Innovative insurance.

PMID- 12073902
TI  - Bon appetit.

PMID- 12073903
TI  - Ownership of cats or dogs does not increase exposure to Rickettsia typhi.
AB  - In the United States, murine typhus (Rickettsia typhi) is endemic in southern
      California and South Texas. Evidence indicates the natural host/vector system is
      the opossum and cat flea, the most common flea on both cats and dogs, and
      speculation suggests that pet contact may pose a risk for R typhi exposure. Serum
      from 140 subjects was tested for rickettsial antibodies by an enzyme-linked
      immunosorbent assay that used an R typhi antigen. Each subject was asked about
      pet contact status and placed in one of the following groups: owners, non-owners
      but with regular contact (more than 3 times per week), non-owners with irregular
      contact (fewer than 3 times per week), or non-owners with no contact. Overall,
      15.7% of sera were positive for antirickettsia IgG. Of owners or those with
      regular contact, 14 of 96 (14.6%) were seropositive, while 8 of 44 (18.2%) of non
      owners or those with irregular contact were seropositive. A chi-square test
      showed no significant difference among these groups (P > .5). We conclude that
      pet ownership or regular contact with pets is not a risk factor for exposure to
      Rickettsia typhi.

PMID- 12073904
TI  - Get rid of bad doctors.

PMID- 12073905
TI  - Reform torts now.

PMID- 12073906
TI  - [Caries in children from ethnic groups. An investigation in five-year-old
      children in Amsterdam and their parents concerning risk indicators and factors].
AB  - A previous study has shown five-year-old children of parents originating from
      Turkey or Morocco to have twice as much dmfs as children of parents from The
      Netherlands, Surinam or various other countries. In the present study, other risk
      indicators and factors for the prevalence of caries amongst these children were
      studied by interviewing their parents at home in their mother tongue about their
      preventive dental behaviour. Results showed educational level of the parents, and
      gender of the child to be important risk indicators, apart from ethnicity. Risk
      factors were the age of the child, at which the parents had started to brush the
      teeth of the child, the use of fluoride tablets and the regularity of the
      brushing behaviour.

PMID- 12073907
TI  - [Reaction to, "Treatment advice from an acupuncturist"].

PMID- 12073908
TI  - [Justus Antoni Wilhelm van Loon, Dr. Med. H.C., D.D.S. (1876-1940). His merits as
      lecturer in orthodontics at the state university in Utrecht (1911-1940)].
AB  - Dr. J. A. W. van Loon (1876-1940) was lecturer of Orthodontics at the Institute
      for Dentistry of the University of Utrecht, the Netherlands. This article
      presents the course of his career, focusing on his education of dental students
      and in his scientific research. He introduced cephalometric diagnostics in
      orthodontics.

PMID- 12073909
TI  - [Long-term effects of preventive dental care in toddlers].
AB  - A study was executed to investigate the relation between the motivation of the
      mother to engage in preventive dental behavior, the level of her school
      education, her place of birth and furthermore the use of fluoride tablets by the
      child in the age period 1 1/2 - 6 years on the one hand and the caries experience
      at the age of 6 and 15 years and the prevalence of fluorosis at the age of 15
      years on the other. The year of birth of the child was taken into account as a
      possible confounding factor. A significant relation was found between the use of
      fluoride tablets and the prevalence of fluorosis. The most important predicting
      factor for the caries experience of the child was the mother's motivation to
      engage in preventive dental behavior. An effect of fluoride tablets on the caries
      experience could not be demonstrated.

PMID- 12073910
TI  - [The Branemark implant in the lower jaw. Experiences of edentate patients with a
      complete implant-supported bridge].
AB  - The Branemark system for implant supported bridges has been carried out in
      Amsterdam since 1982. One hundred patients with a maxillary conventional full
      denture and a mandibular fixed tissue-integrated prosthesis were selected for
      this study. Before and long after the treatment, questionnaires were sent to
      these patients in order to gain information of their experiences. The treatment
      had greatly benefitted the patients, in spite of the problem of the loose lower
      denture in some cases was shifted to the upper jaw.

PMID- 12073911
TI  - [Surgical jaw orthopedics. The keen and cutting view].

PMID- 12073912
TI  - [Illuminating the face].

PMID- 12073913
TI  - [STG report Future Scenario's Dentistry].

PMID- 12073914
TI  - [Reaction to "The dentist in love"].

PMID- 12073915
TI  - Code of ethics?

PMID- 12073916
TI  - Getting staff and patients to like you.

PMID- 12073917
TI  - Going private.

PMID- 12073918
TI  - Have your say.

PMID- 12073919
TI  - Free wheeling.

PMID- 12073920
TI  - You shall go to the ball.

PMID- 12073922
TI  - In the hot seat.

PMID- 12073921
TI  - Use it or lose it.

PMID- 12073924
TI  - Home is where the heat is.

PMID- 12073923
TI  - Goodbye to grey days.

PMID- 12073925
TI  - Seaside soundbites.

PMID- 12073926
TI  - A new start.

PMID- 12073928
TI  - Let's go surfing.

PMID- 12073927
TI  - Yours in confidence.

PMID- 12073929
TI  - Life, the universe and you.

PMID- 12073930
TI  - Question time.

PMID- 12073931
TI  - Tyrosine phosphatase-like protein (IA-2) and glutamic acid decarboxylase (GAD65)
      autoantibodies: a study of Chinese patients with diabetes mellitus.
AB  - Type 1 diabetes in most Asian populations may not have a salient autoimmune basis
      when assessed with single determinations of the major markers, islet cell
      antibodies (ICAs) and glutamic acid decarboxylase antibodies (GAD65ab). With the
      inclusion of antibodies to tyrosine phosphatase-like protein IA-2 (IA-2ab) as an
      additional major marker, we re-examined autoimmune diabetes in a group of Chinese
      patients. We studied 272 subjects at various stages of disease with blood samples
      procured for biochemical analysis. ICAs were measured by immunofluorescence,
      GAD65ab and IA-2ab by radioimmunoassay. Sixty-seven patients fulfilled clinical
      diagnosis of type 1 diabetes and the remaining 205 patients were type 2.
      Prevalence of single autoantibody type in recent-onset type 1 diabetes ( < 1 year
      duration; n = 47) showed 10.6% with ICAs, 44.7% GAD65ab and 36.2% IA-2ab. GAD65ab
      account for more than two-thirds of the markers found in type 1 diabetes.
      Combined analysis further showed that 51.1% had at least one antibody type, 31.9%
      with two or more antibodies and 8.5% with all three antibodies. Islet
      autoimmunity presence in childhood-onset type 1 diabetes improved with the
      addition of IA-2ab, though less impact was seen in the adult-onset. Similarly,
      combined analysis for type 2 patients with recent diabetes showed a modest
      increase to 13% with islet autoimmunity compared to 8% when assessed by GAD65ab
      alone. Combining IA-2ab and GAD65ab assays results detected slightly more immune
      mediated diabetes, compared to using a single GAD65ab determination. Non
      autoimmune causes need to be considered in the pathogenesis of type 1 diabetes in
      Chinese, particularly in adults.

PMID- 12073933
TI  - Aggregation characteristics of ovalbumin in beta-sheet conformation determined by
      spectroscopy.
AB  - Protein misfolding and aggregation are involved in a number of the so-called
      "conformational" diseases (e.g., transmissible spongiform encephalopathies and
      Alzheimer disease). The development of rational strategies to interfere with
      aggregation is a potential therapeutic approach that requires complete knowledge
      of the aggregation process. We studied the aggregation of ovalbumin in beta-sheet
      conformation using mainly the spectral changes in the spectra of two dyes (Congo
      Red and pinacyanol) caused by the aggregates. We assumed a linear model of
      polymerization that fit to the experimental data. The critical aggregation
      constant, concentration of half-aggregation, nucleation parameter, growth
      parameter, and number of aggregation and free energy changes (total and per
      residue) were determined as aggregation-related parameters. Beta-Ovalbumin
      aggregates in a cooperative way. Moreover, the differences between such
      parameters obtained with Congo Red and pinacyanol suggest that each dye interacts
      with the protein in its own way.

PMID- 12073932
TI  - Spectroscopic study on structure of horseradish peroxidase in water and dimethyl
      sulfoxide mixture.
AB  - The structure of horseradish peroxidase (HRP) in phosphate buffered saline
      (PBS)/dimethyl sulfoxide (DMSO) mixed solvents at different compositions is
      investigated by IR, electronic absorption, and fluorescence spectroscopies. The
      fluorescence spectra and the amide I spectra of ferric HRP [HRP(Fe3+)] show that
      overall structural changes are relatively small up to 60% DMSO. Although the
      amide I band of HRP(Fe3+) shows a gradual change in the secondary structure and a
      decrease in the contents of a helices, its fluorescence spectra indicate that the
      distance between the heme and Trp173 is almost constant. In contrast, the changes
      in the positions of the Soret bands for resting HRP(Fe3+) and catalytic
      intermediates (compounds I and II) and the IR spectra at the C-O stretching
      vibration mode of carbonyl ferrous HRP [HRP(Fe2+)-CO] show that the
      microenvironment in the distal heme pocket is altered, even with low DMSO
      contents. The large reduction of the catalytic activity of HRP even at low DMSO
      contents can be attributed to the structural transition in the distal heme
      pocket. In PBS/DMSO mixtures containing more than 70 vol % DMSO, HRP undergoes
      large structural changes, including a large loss of the secondary structure and a
      dissociation of the heme from the apoprotein. The presence of the components of
      the amide I band that can be assigned to strongly hydrogen bonding amide C=O
      groups at 1616 and 1684 cm(-1) suggests that the denatured HRP may aggregate
      through strong hydrogen bonds.

PMID- 12073935
TI  - Fourier Transform-Raman spectroscopic study of natural resins of archaeological
      interest.
AB  - Resins from several different genera are studied using Fourier transform (FT)
      Raman spectroscopy. Tree resins can be broadly divided into those that contain
      diterpenoid components and those that contain triterpenoid components. The
      diterpenoid resins analyzed are from the genera Pinus, Cedrus, and Agathis (kauri
      resin) and the triterpenoid resins examined are samples from Pistacia, Boswellia
      (frankincense), and Commiphora (myrrh) genera. A protocol is developed to
      nondestructively distinguish diterpenoid and triterpenoid resins and to
      differentiate the genera within the two types. The effects of oxidation on the
      discrimination of the FT-Raman spectra are considered.

PMID- 12073934
TI  - Dynamics of supercoiled and linear pTZ18U plasmids observed with a long-lifetime
      metal-ligand complex.
AB  - The metal-ligand complex, [Ru(bpy)2(dppz)]2+ (bpy = 2,2'-bipyridine, dppz =
      dipyrido[3,2-a:2',3'-c]phenazine) (Ru-BD), was used as a spectroscopic probe for
      studying nucleic acid dynamics. The Ru-BD complex displays a long lifetime of
      over 100 ns and a molecular light switch property upon DNA binding due to
      shielding of its dppz ligand from water. To further show the usefulness of this
      luminophore (Ru-BD) for probing DNA dynamics, we examined its intensity and
      anisotropy decays when intercalated into supercoiled and linear pTZ18U plasmids
      using frequency-domain fluorometry with a light-emitting diode (LED) as the
      modulated light source. Compared to the supercoiled plasmids with an average
      intensity decay time of 120.8 ns at 25 degrees C, we obtained somewhat longer
      lifetimes for the linear plasmids ((tau) = 141.4 ns at 25 degrees C), suggesting
      a more efficient shielding from water by the linear plasmids. The anisotropy
      decay data also showed longer rotational correlation times for the linear
      plasmids (495 and 35 ns at 25 degrees C) as compared to the supercoiled plasmids
      (412 and 27 ns at 25 degrees C). The slow and fast rotational correlation times
      appear to be consistent with the bending and torsional motions of the plasmids,
      respectively. The anisotropy values were quite similar, although the values of
      the supercoiled plasmids were slightly higher in both the steady-state and
      anisotropy decay measurements. These results indicate that Ru-BD can be applied
      in the study of both bending and torsional dynamics of nucleic acids.

PMID- 12073936
TI  - Effect of molecular confinement on internal enzyme dynamics: frequency domain
      fluorometry and molecular dynamics simulation studies.
AB  - The tryptophanyl emission decay of the mesophilic beta-galactosidase from
      Aspergillus oryzae free in buffer and entrapped in agarose gel is investigated as
      a function of temperature and compared to that of the hyperthermophilic enzyme
      from Sulfolobus solfataricus. Both enzymes are tetrameric proteins with a large
      number of tryptophanyl residues, so the fluorescence emission can provide
      information on the conformational dynamics of the overall protein structure
      rather than that of the local environment. The tryptophanyl emission decays are
      best fitted by bimodal Lorentzian distributions. The long-lived component is
      ascribed to close, deeply buried tryptophanyl residues with reduced mobility; the
      short-lived one arises from tryptophanyl residues located in more flexible
      external regions of each subunit, some of which are involved in forming the
      catalytic site. The center of both lifetime distribution components at each
      temperature increases when going from the free in solution mesophilic enzyme to
      the gel-entrapped and hyperthermophilic enzyme, thus indicating that confinement
      of the mesophilic enzyme in the agarose gel limits the freedom of the polypeptide
      chain. A more complex dependence is observed for the distribution widths.
      Computer modeling techniques are used to recognize that the catalytic sites are
      similar for the mesophilic and hyperthermophilic beta-galactosidases. The effect
      due to gel entrapment is considered in dynamic simulations by imposing harmonic
      restraints to solvent-exposed atoms of the protein with the exclusion of those
      around the active site. The temperature dependence of the tryptophanyl
      fluorescence emission decay and the dynamic simulation confirm that more rigid
      structures, as in the case of the immobilized and/or hyperthermophilic enzyme,
      require higher temperatures to achieve the requisite conformational dynamics for
      an effective catalytic action and strongly suggest a link between conformational
      rigidity and enhanced thermal stability.

PMID- 12073937
TI  - Near-IR spectroscopic imaging for skin hydration: the long and the short of it.
AB  - Near-IR spectroscopic methods have been developed to determine the degree of
      hydration of human skin in vivo. Noncontact reflectance spectroscopic imaging was
      used to investigate the distribution of skin moisture as a function of location.
      A human study in a clinical setting has generated quantitative data showing the
      effects of a drying agent and a moisturizer on delineated regions of the forearms
      of eight volunteers. Two digital imaging systems equipped with liquid-crystal
      tunable filters were used to collect stacks of monochromatic images at 10-nm
      intervals over the 650-1050 and 960-1700 nm wavelength bands. Synthetic images
      generated from measurements of water absorption band areas at three different
      near-IR wavelengths (970, 1200, and 1450 nm) showed obvious differences in the
      apparent distribution of water in the skin. Changes resulting from the skin
      treatments were much more evident in the long-wavelength images than in the short
      wavelength ones. The variable sensitivity of the method at different wavelengths
      has been interpreted as being the result of different penetration depths of the
      IR light used in the reflectance studies.

PMID- 12073938
TI  - In vitro: a whites-only therapy, but everyone pays (through the nose) for it.

PMID- 12073939
TI  - "Outing" religion in bioethics.

PMID- 12073940
TI  - Finding common ground: religion's role in the ethics committee.

PMID- 12073941
TI  - To tell or not to tell: must the doctors inform her she'll be infertile?

PMID- 12073942
TI  - Posting five precepts: a Buddhist perspective on ethics in health care.

PMID- 12073943
TI  - A tale of two creatures: Jewish and Christian attitudes toward cloning.

PMID- 12073944
TI  - Patient self-management in ulcerative colitis: a radical realignment in the
      physician-patient relationship.

PMID- 12073946
TI  - Blame Canada: growing questions about budesonide.

PMID- 12073945
TI  - Seminal work: azathioprine and male fertility in inflammatory bowel disease.

PMID- 12073947
TI  - Circulatory, respiratory and metabolic changes after thigh tourniquet release in
      combined epidural-propofol anaesthesia with preservation of spontaneous
      respiration.
AB  - Twelve elderly patients undergoing total knee arthroplasty received lumbar
      epidural anaesthesia and propofol infusion at 5 mg.kg(-1).h(-1) following a 1.5
      2.0 mg.kg(-1) bolus dose with preservation of spontaneous respiration via a
      laryngeal mask airway. Circulatory, respiratory and metabolic variables were
      measured before and 1, 3, 5, 15 and 30 min after release of a pneumatic thigh
      tourniquet. The blood pressure was decreased at all time-points and the
      respiratory rate increased at 1 min. The P(a)CO(2) was increased only at 1 min.
      Arterial blood pH and base excess were decreased at 1 and 3 min and 1, 3 and 5
      min, respectively. Arterial blood lactate levels were increased at all times.
      These characteristics were considered to be identical to those under regional
      anaesthesia with conscious spontaneous respiration, showing that spontaneous
      respiration under this anaesthetic regimen has a similar respiratory capacity to
      that of conscious spontaneous respiration.

PMID- 12073948
TI  - Aseptic precautions for inserting an epidural catheter: a survey of obstetric
      anaesthetists.
AB  - We performed a postal survey of Fellows of the Australian and New Zealand College
      of Anaesthetists with a special interest in obstetric practice, about their
      beliefs regarding aseptic precautions for insertion of an epidural catheter in
      the labour ward. Of the 435 consultant anaesthetists surveyed, 367 responded
      (84%), revealing a wide variation in practice. It was not thought to be essential
      practice to remove a watch before washing hands by 51 respondents (14%), to wear
      a facemask by 105 (29%) or to wear a sterile gown by 45 (12%). Three
      anaesthetists (1%) did not believe sterile gloves were essential. However, all
      respondents indicated that an antiseptic skin preparation was essential. Our
      results raise questions regarding an acceptable standard of aseptic practice for
      the insertion of an epidural catheter in labour and we propose a minimal standard
      of essential precautions.

PMID- 12073949
TI  - Comparison of external jugular and central venous pressures in mechanically
      ventilated patient.
AB  - We compared central venous pressures, measured via a 150 mm triple lumen catheter
      in the internal jugular vein with simultaneous external jugular venous pressures,
      measured with a 5 mm cannula in the external jugular vein, in 24 patients
      undergoing major surgery. Patients were mechanically ventilated in the supine
      position. Six sets of paired measurements of mean central venous pressure and
      mean external jugular venous pressure were taken by a blinded observer, in random
      order and at end-expiration at 30-min intervals during surgery. Four patients
      were not studied because of a failure to cannulate the external jugular vein. The
      remaining 20 patients yielded 111 sets of paired measurements. The mean
      difference between external jugular venous pressure and central venous pressure
      was 0.3 mmHg over a range of central venous pressure of 0-22 mmHg. Limits of
      agreement were 3.6 to +3.0 mmHg (95% CI 4.1 to +3.5 mmHg). We conclude that
      external jugular venous pressure is an accurate estimate of central venous
      pressure in surgical patients undergoing mechanical ventilation.

PMID- 12073950
TI  - Partner anxiety prior to elective Caesarean section under regional anaesthesia.
AB  - This study was designed to measure anxiety levels in 91 partners of women
      undergoing elective Caesarean section under regional anaesthesia and to outline
      potential relieving factors. Twenty-eight percent of partners were pathologically
      anxious. There was a positive association between anxiety and prior attendance at
      the anaesthetic assessment clinic (p=0.008). There was no statistically
      significant association between anxiety and education, occupation, gender,
      relationship to the patient or previous attendance at Caesarean section. Concern
      about a safe outcome for the mother and child caused most anxiety, less being
      expressed regarding presence in the operating theatre or anaesthesia per se. Over
      70% of partners expressed the view that attendance at the anaesthetic assessment
      clinic or provision of written information would reduce their anxiety.

PMID- 12073951
TI  - Is puberty getting earlier? The views of doctors and teachers.
AB  - AIMS: To determine the views of teachers, general practitioners (GPs) and
      paediatricians about whether there has been a recent change in the timing of the
      onset of puberty in children in the UK and in the timing of menarche in girls.
      DESIGN: Questionnaires were sent to a stratified random sample of each
      professional group. RESULTS: In relation to girls, almost 80% of teachers believe
      that the onset of puberty is occurring earlier and 73% feel that the menarche is
      occurring earlier. Those who had been working for longer than 10 years were more
      likely to say that the age of onset of puberty had decreased. GPs feel that both
      puberty and menarche are starting earlier, whereas paediatricians were evenly
      divided between those who thought puberty was starting earlier and those who
      thought that the timing had not changed. In boys, professionals generally believe
      that the timing of the onset of puberty has not altered significantly.
      CONCLUSION: Further study is required to determine whether puberty is really
      occurring earlier in girls.

PMID- 12073952
TI  - Interdisciplinary health care training in the USA: lessons learned from a rural
      training grant program.

PMID- 12073953
TI  - Strategies used by interdisciplinary rural health training programs to assure
      community responsiveness and recruit practitioners.
AB  - In this article, the strategies used by five US rural interdisciplinary training
      grant programs to respond to local needs and to promote recruitment in rural
      communities are described. The programs provide training to 17 health care
      disciplines and serve disadvantaged Hispanic, African-American, Amish, Native
      American, and Anglo populations. Four programs are based in academic
      institutions; one is based in a community health center. The programs provide
      services to the rural communities through individual clinical or case management
      services, population-level interventions, and collaborative research. All
      programs use specific mechanisms (e.g. case conferences or participation in local
      coalitions) to facilitate collaboration with residents and to link student
      activities with community or individual needs. Unique strategies include the use
      of problem-based learning and community health workers on the interdisciplinary
      team to increase responsiveness. The programs also provide educational support to
      students while they work in the rural communities. Finally, the primary strategy
      used to promote recruitment is the training experience in rural communities. The
      programs also appear to indirectly improve the environment of rural practice.

PMID- 12073954
TI  - Congenital bilary atresia: report of three cases, two occurring in one family.
      Whitten WW, Adie GC. J Pediatr 1952;40:539-48.

PMID- 12073955
TI  - Malformations of the brain: a neglected source of basic knowledge on the
      development of cerebral structure and function. Yakolev P I. J Pediatr
      1952;40:626-7.

PMID- 12073957
TI  - Did eugenics ever die?

PMID- 12073956
TI  - Initial experience with minimally invasive in situ bypass procedure with blind
      valvulotomy.
AB  - OBJECTIVE: The in situ vein (ISV) bypass is uniquely suited to technical
      modifications designed to reduce the wound morbidity of infrainguinal
      revascularization. A technique of "blind" valvulotomy and selective vein branch
      ligation was used, and a preliminary study was performed to assess safety and
      efficacy. METHODS: From November 1998 to July 2001, all patients for
      infrainguinal bypass procedures underwent evaluation for inclusion in the study.
      Thirty-five patients underwent ISV bypass procedures with an expandable, self
      centering valvulotome (ESV). Intraoperative selection of veins suitable for the
      study was assisted with venography and duplex scanning. The ISV bypass procedures
      were performed with initial groin and distal incisions, with smaller incisions to
      ligate significant arteriovenous fistulae (AVF). Duplex graft scanning was
      performed at routine intervals after surgery. RESULTS: Thirty-seven ISV grafts
      were performed from the common femoral artery to the popliteal (n = 14), tibial
      (n = 20), and dorsalis pedis (n = 3) arteries. In 35 cases (95%), a full-length
      incision was avoided. With ESV, all valves in 34 cases (92%) were effectively
      lysed. Proximal extension of the distal incision was performed in four cases
      (10.8%). The mean number of incisions per case was 3.1 +/- 1.7. One graft failed
      within 30 days (2.7%), with successful revision. During the early follow-up
      period (9.9 +/- 7.3 months; range, 1 to 33 months), 44% of residual AVF closed
      spontaneously (15 of 34 AVF; 16 patients) and two anastomotic stenoses and two
      symptomatic AVF were corrected surgically. Four late graft occlusions occurred,
      with a 1-year cumulative primary patency rate of 77% and a secondary patency rate
      of 92%. CONCLUSION: Blind valvulotomy with ESV facilitates safe and effective
      minimally invasive ISV bypass. Resultant graft patency rates appear comparable
      with results with open techniques. This preliminary experience warrants further
      study to refine patient selection criteria and operative technique and to better
      clarify the natural history of residual AVF.

PMID- 12073958
TI  - The impact of self-monitoring of blood glucose on self-efficacy and pregnancy
      outcomes in women with diet-controlled gestational diabetes.
AB  - PURPOSE: The purpose of this study was to examine the effects of self-monitoring
      of blood glucose (SMBG) on feelings of self-efficacy, dietary compliance, and
      pregnancy outcomes in women with diet-controlled gestational diabetes mellitus
      (GDM). METHODS: Fifty-eight women with GDM and a fasting blood glucose level < 95
      mg/dL were randomly assigned to 2 groups. The experimental group measured their
      blood glucose levels 4 times daily using a reflectance meter with memory.
      Metabolic status was assessed in the control group by periodic monitoring at
      prenatal visits. Otherwise the management protocol was identical for both groups.
      The Diabetes Empowerment Scale was completed at study entry and at 37 weeks
      gestation to assess feelings of self-efficacy. Dietary compliance was assessed at
      each visit. RESULTS: Both groups of women achieved excellent glucose control;
      only 1 woman in each group required insulin therapy. There were no significant
      differences with regard to feelings of self-efficacy, dietary compliance, birth
      weight, gestational age at delivery, Apgar scores, and neonatal complications.
      Rates of macrosomia, delivery by cesarean section, and occurrence of birth trauma
      were similar. CONCLUSIONS: SMBG appears to have little effect on maternal
      feelings of self-efficacy, dietary compliance, or pregnancy outcomes in women
      with diet-controlled GDM.

PMID- 12073959
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12073960
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12073961
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12073962
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12073963
TI  - Re: Long-term efficacy of sildenafil and tachyphylaxis effect.

PMID- 12074019
TI  - [First medical treatment in respiratory and digestive system blood. From the
      series of examples of "first medical treatment", organized by the Medical
      Organization in Prussia, Winter semester 1904/05].

PMID- 12074020
TI  - [Treatment of cerebrovascular accident].

PMID- 12074021
TI  - Strategy for rapid immobilization of prey by a fish-hunting marine snail.
AB  - Some venomous animals capture prey with remarkable efficiency and speed. The
      purple cone, Conus purpurascens, uses two parallel physiological mechanisms
      requiring multiple neurotoxins to immobilize fish rapidly: neuromuscular block,
      and excitotoxic shock. The latter requires the newly characterized peptide kappa
      conotoxin PVIIA, which inhibits the Shaker potassium channel 2-4, and beta
      conotoxin PVIA5, which delays sodium-channel inactivation. Despite the extreme
      biochemical diversity in venoms, the number of effective strategic alternatives
      for prey capture are limited. How securely prey is initially tethered may
      strongly influence the venom strategy evolved by a predator.

PMID- 12074022
TI  - Carcinogenicity studies after intraperitoneal injection of two types of stone
      wool fibres in rats.
AB  - A summary is given of the pathology results after intraperitoneal (i.p.)
      injection in rats of insulation wool HT, representing the new biosoluble types.
      The pathology results are compared with a previously conducted i.p. study with
      traditional stone wool D6 (with similar chemical composition to MMVF21). The HT
      fibre is characterized by a relatively high content of aluminium and a relatively
      low content of silica compared to MMVF21. HT has a high in vitro dissolution rate
      at pH 4.5, a relatively low dissolution rate at pH 7.5 and is less biopersistent
      than the MMVF21 fibre. Female Wistar rats received a dose of 2 x 10(9) WHO HT
      fibres by i.p. injection. The fibres had been size-selected to be largely rat
      respirable. The negative control group was exposed to saline. Following exposure,
      the animals were maintained until survival in one group fell below 20%. At this
      time, all animals were killed. All animals were subjected to a necropsy
      examination; any gross abnormalities observed at necropsy were subjected to
      histopathological examination. In addition, histopathology was carried out on a
      predefined list of tissues. The incidences of lesions and survival in the control
      and fibre dosed animals were compared using appropriate statistical methods to
      determine whether the dosed animals showed adverse effects on survival or a
      positive carcinogenic response. The main protocol for the previously conducted
      study with D6 (MMVF21) was similar, but the animals were maintained as long as
      they survived, and the WHO fibre dose was lower. The results of the comparative
      study showed a marked difference in the i.p. pathogenicity of D6 (MMVF21) and HT
      in terms of their carcinogenic potential. D6 (MMVF21) caused a statistically
      significant increase of mesotheliomas in the peritoneal cavity compared to the
      negative control, but the HT fibre did not cause any mesotheliomas or any
      increase in other tumour types.

PMID- 12074023
TI  - The effect on heart rate and facial skin temperature of wearing respiratory
      protection at work.
AB  - Twelve New Zealand workers from a range of occupations were studied to
      investigate the effect of wearing air-filtering respiratory protection on heart
      rate (HR) and facial skin temperature (Tlip and Tcheek) whilst working. All
      variables were measured continuously during simulated and actual work. The former
      allowed physiological measurements to be undertaken during the physical
      activities carried out during the work task without respirators and without
      exposure to hazardous airborne substances. Mean heart rates in subjects moving
      without respirators ranged from 75 to 94 beats/min and from 77 to 98 beats/min
      during respirator use at work. Mean skin temperature under the mask (Tlip)
      increased in 11 of the 12 subjects while using respirators (range 1.2-4.8 degrees
      C) but Tcheek only increased in four (range 0.6-1.5 degrees C). The use of
      simulated work tasks in the experiment was a compromise. The heart rate data from
      the real and simulated work indicated that effort and workload, though not
      identical, were similar. The increase in skin temperature under the mask may
      account for the reluctance of individuals to wear respiratory protection at work.
      This region of the face is very thermosensitive.

PMID- 12074024
TI  - Compliance with the manual handling regulations amongst a random selection of
      small businesses in England.
AB  - Manual handling activities have long been recognized as major contributors to
      occupational injury and ill health. Following a series of consultative documents,
      the Manual Handling Operations Regulations (MHORs) and their associated Guidance
      came into force in the UK in January 1993. More than 5 yr on, an investigation
      was performed to evaluate response to this legislation amongst a random selection
      of small businesses within a business district of Shropshire, England. A postal
      questionnaire was sent to 100 companies employing 5-50 workers. Responses were
      obtained from 80 companies, ranging from retailing to metals/engineering.
      Although all of the companies are likely to perform activities requiring manual
      handling assessments under the MHORs, many claimed never to have heard of the
      legislation (38%) and almost half (46%) had not performed an assessment.
      Compliance varied significantly by business type, with the nine companies engaged
      in metals/engineering reporting significantly better compliance (P < 0.05). Of
      the 43 companies who claimed to have undertaken assessments, 73% (32 companies)
      indicated that manual handling activities had been changed, with all claiming to
      have reduced lifting activities, a significant proportion (75%) making
      improvements to the working environment and over half (59%) reducing the weight
      of loads. Many of the companies who indicated full compliance with the
      legislation (21 companies) stated that the benefits to their businesses
      outweighed the cost of compliance. Additional factors analysed by the study
      include source of legislative awareness, personnel performing assessments,
      employee training and method used, and reasons for non-compliance with the MHORs.

PMID- 12074025
TI  - Temperature limit values for gripping cold surfaces.
AB  - OBJECTIVES: At the request of the European Commission and in the framework of the
      European Machinery Directive, research was conducted jointly in five different
      laboratories to develop specifications for surface temperature limit values for
      the gripping and handling of cold items. METHODS: Four hundred and fourteen
      experiments were run where male and female subjects were invited to grip for up
      to 20 min cold bars of different contact coefficients, i.e. polished wood, nylon,
      stone, steel and aluminium. The air temperature and the bars' initial surface
      temperatures ranged between 0 and -30 degrees C for the various experiments.
      While gripping the bars, either only the hand or the whole body was exposed to
      cold. RESULTS: The data were used to develop a prediction formula and a graph of
      the surface temperature limit values in order for the skin contact temperature
      not to reach <15 degrees C. This duration is shown to offer a significant degree
      of safety with respect to the minimal surface temperature spontaneously tolerated
      by the subjects. CONCLUSIONS: Experiments and modelling must be pursued to extend
      these data to other conditions of exposure.

PMID- 12074026
TI  - A valid method for comparing rational and empirical heat stress indices.
AB  - No single heat stress index has gained universal acceptance within the past 20
      years, despite extensive research. It is currently difficult to directly and
      quantitatively compare the many rational and empirical indices that are
      available, which results in confusion and a reluctance to change to a different
      index. A method is developed using the concept of limiting metabolic rate, which
      allows virtually all heat stress indices to be compared with one another. Because
      all occupational heat stress indices are based, explicitly or implicitly, on the
      human heat balance equation, a unique value of metabolic rate can be found that
      just allows an unrestricted work/rest cycle in particular environmental
      conditions. A comparison using this methodology shows that there are very large
      differences between the recommended limits under the various indices, even for
      similar populations of acclimatized workers.

PMID- 12074027
TI  - Time extrapolation and interspecies extrapolation for locally acting substances
      in case of limited toxicological data.
AB  - In the case of substances with a limited toxicological data base there is often
      (i) a lack of qualified human toxicological data; and (ii) a paucity of studies
      with adequate exposure duration. Hence, several extrapolations have to be
      performed to arrive at appropriate risk assessments or derive occupational
      exposure limits. The present paper deals with the possibilities for extrapolating
      the change in effect concentrations over time (time extrapolation, e.g. from
      subacute to chronic exposure) and for interspecies extrapolation (from animal to
      human) in connection with locally acting substances (respiratory toxicants). To
      justify the time extrapolation factors, 46 technical reports produced by the US
      National Toxicology Program (NTP) involving studies with subacute, subchronic and
      chronic exposure duration were evaluated. On the basis of geometric mean values,
      decreases in effect concentrations by factors of 3.2 (subacute --> subchronic),
      2.7 (subchronic --> chronic) and 6.6 (subacute --> chronic) were found.
      Differentiation according to animal species (mouse, rat), sex or substance
      properties did not result in any relevant changes of the mean value. NTP studies
      with less than lifetime exposure periods (subacute, subchronic) in many cases
      showed different locations of respiratory effects compared with chronic studies,
      and thus offered limited possibilities for qualitative prediction of long-term
      respiratory effects (occurrence of effects in certain regions of the respiratory
      tract). With regard to interspecies extrapolation, gaseous and particulate
      substances were evaluated separately. With some modifications (e.g. consideration
      of the clearance of particles of low solubility), the 1994 US Environmental
      Protection Agency (EPA) model for deriving reference concentrations for humans on
      the basis of experimental data in animals is proposed for inhalable particulate
      substances. In the case of gaseous substances, the assumptions of the EPA model
      do not seem to consider sufficiently the local inhomogeneity in substance
      distribution and anatomical and histological differences between the upper
      respiratory tracts of rodents and humans. Considerable uncertainty would attach
      to a default factor for interspecies extrapolation for gaseous substances.

PMID- 12074028
TI  - Passive sampler used for simultaneous measurement of breathing zone size
      distribution, inhalable dust concentration and other size fractions involving
      large particles.
AB  - The particle size-dependent sampling velocity of the passive dust sampler
      developed by Vinzents (1996) is investigated under field conditions.
      Microscopical determination of the projected area equivalent diameter is used to
      quantify particles deposited on the sampler foils. Parameters for a semi
      empirical model for particle deposition velocities on upward and forward facing
      foils are fitted to the data and it is shown that deposition mechanisms other
      than gravitational settling on the upward facing foil can be neglected. For
      calculation of airborne mass concentration no information on particle density is
      needed and only the ratio between the dynamic and volume shape factors needs to
      be known. Given the sampling velocity, the airborne mass per diameter interval is
      calculated from samples obtained in the wood industry, from which inhalable dust
      concentrations are calculated. The results are in line with parallel samples
      obtained with an inhalable dust sampler. A 'total' dust sampling characteristic
      can be fitted which reproduces measured 'total' dust with a closed face monitor.
      The results of this study demonstrate the validity of the passive dust sampling
      principle in environments involving even large (>100 microm) particles and the
      potential to predict the concentration of several size fractions.

PMID- 12074029
TI  - Performance testing of three portable, direct-reading dust monitors.
AB  - Three portable direct-reading dust monitors were tested in a recirculating dust
      tunnel and a calm air dust chamber against a range of industrial dusts with
      different size distributions to investigate sources of variation in their
      responses. Responses were found to be linear compared to reference gravimetric
      respirable samplers over a range of concentrations for a particular particle size
      distribution. Their calibration factors were dependant on particle size, particle
      composition and air velocity. If particle size and air velocity do not change
      significantly then the calibration factor can be applied to the monitor readings
      to give an accurate measure of dust concentration. The DataRam and HAM, factory
      calibrated against respirable dust concentration, were found to agree closely,
      whereas the Microdust gave higher readings, having been factory calibrated
      against total suspended particulate concentration. The calibration of the DataRam
      was significantly altered by either contamination of the optics with dust or by
      cleaning the optics. This was not observed with either the Microdust or HAM,
      since both monitors include a reference calibration element.

PMID- 12074030
TI  - A Dirichlet Tessellation-based sampling scheme for measuring whole-body exposure.
AB  - Dermal sampling can be conducted using small pads or patches attached to various
      areas of the skin or clothing, or by using a whole-body coverall. Both techniques
      are recognized standardized methods for collecting chemicals. Patch sampling is
      simple to perform and inexpensive to analyse compared with an entire overall, but
      may require some user intervention. Extrapolation from a small sampled area to
      the total body area can lead to inaccurate estimates of total body exposure
      because of a lack of uniformity of deposition. Whole-body overall analysis
      eliminates the problems associated with using patches and gives a more accurate
      estimate of total body exposure. Therefore, if it were possible to measure the
      whole-body overall accurately and quickly, we would have a better assessment of
      dermal exposure. In this study we develop a working protocol using a standardized
      approach, to measure the contamination over an entire overall. The protocol takes
      into account size differences and establishes a reproducible pattern of sampling
      in order to map the distribution of contamination over each overall. The working
      protocol has been applied to 10 overalls collected from companies using copper
      based biocides. A portable X-ray fluorescence spectrometer (PXRF) was used to
      measure the copper in the biocide. The exposure estimate from the PXRF results
      uses an averaging scheme based on the Dirichlet tessellation of the sampling
      locations. This allows unbiased estimates to be obtained from a complex sampling
      scheme that allocates more measurements to areas of high exposure. The Dirichlet
      tessellation method has been compared to the patch sampling method and the
      conventional total digestion of the entire overall method. Using the whole-suit
      digestion method as the benchmark, exposures ranged from 92.0 to 5848.5 mg. Mean
      absolute percentage errors (from the benchmark acid digestion of the whole suit)
      varied from approximately 20% for the Dirichlet-based PXRF method to 60% for the
      patch methods. The patch methods underestimated the true dermal exposure (-28 to 
      82% for acid digestion of the patches). Analysis of this data indicates that the
      Dirichlet PXRF method gives a more accurate estimate of whole-body contamination
      than the patch method. Furthermore, the 104 measurements give a much greater
      spatial resolution to the exposure data than analysis of the whole overall or
      patches by inductively coupled plasma-atomic emission mass spectrometry (ICP
      AES). This detailed knowledge of the pattern of deposition on the body is of
      potential importance in chemical risk assessments.

PMID- 12074031
TI  - Sample size considerations for studies of intervention efficacy in the
      occupational setting.
AB  - OBJECTIVE: Due to a shared environment and similarities among workers within a
      worksite, the strongest analytical design to evaluate the efficacy of an
      intervention to reduce occupational health or safety hazards is to randomly
      assign worksites, not workers, to the intervention and comparison conditions.
      Statistical methods are well described for estimating the sample size when the
      unit of assignment is a group but these methods have not been applied in the
      evaluation of occupational health and safety interventions. We review and apply
      the statistical methods for group-randomized trials in planning a study to
      evaluate the effectiveness of technical/behavioral interventions to reduce wood
      dust levels among small woodworking businesses. METHODS: We conducted a pilot
      study in five small woodworking businesses to estimate variance components
      between and within worksites and between and within workers. In each worksite, 8
      h time-weighted dust concentrations were obtained for each production employee on
      between two and five occasions. With these data, we estimated the parameters
      necessary to calculate the percent change in dust concentrations that we could
      detect (alpha = 0.05, power = 80%) for a range of worksites per condition,
      workers per worksite and repeat measurements per worker. RESULTS: The mean wood
      dust concentration across woodworking businesses was 4.53 mg/m3. The measure of
      similarity among workers within a woodworking business was large (intraclass
      correlation = 0.5086). Repeated measurements within a worker were weakly
      correlated (r = 0.1927) while repeated measurements within a worksite were
      strongly correlated (r = 0.8925). The dominant factor in the sample size
      calculation was the number of worksites per condition, with the number of workers
      per worksite playing a lesser role. We also observed that increasing the number
      of repeat measurements per person had little benefit given the low within-worker
      correlation in our data. We found that 30 worksites per condition and 10 workers
      per worksite would give us 80% power to detect a reduction of approximately 30%
      in wood dust levels (alpha = 0.05). CONCLUSIONS: Our results demonstrate the
      application of the group-randomized trials methodology to evaluate interventions
      to reduce occupational hazards. The methodology is widely applicable and not
      limited to the context of wood dust reduction.

PMID- 12074032
TI  - Urinary 1-hydroxypyrene as a biomarker of internal dose of polycyclic aromatic
      hydrocarbons in carbon black workers.
AB  - In this study, a total of 30 workers were selected, including eight wet
      pelletizing workers and 22 packaging workers. For all selected workers, urine
      samples were collected on the first day pre-shift, first day post-shift and fifth
      day post-shift, and their urinary 1-hydroxylpyrene levels (1-OHP) were determined
      (denoted as BM1pre, BM1post and BM5post, respectively). Personal respiratory
      exposures, including both inhalable particle-bound PAHs (Cinh) and gaseous PAHs
      (Cgas), together with dermal exposure to particle-bound PAHs (Cskin) were
      measured. Personal background information, including age, sex and smoking habit,
      was carefully registered. Pyrene exposure was statistically significantly
      correlated with exposure to PAHs and carcinogenic PAHs. Multiple linear
      regression analysis results showed that the BM1post values could not be explained
      by workers' exposures. For BM5post in packaging workers, both the regression
      model (R2 = 0.73) and the regression coefficients for Cgas, Cinh and Cskin were
      statistically significant (P < 0.05). For pelletizing workers, the R2 value was
      higher but was not statistically significant because of the smaller number of
      workers. The resultant regression coefficients for 'sex', 'smoking habit' and
      'age' were statistically insignificant (P >> 0.05), which could be because these
      variables made relatively small contributions to BM5post. In conclusion, this
      study suggests BM5post could be a suitable indicator for PAH exposures of carbon
      black workers, on the condition that both respiratory (including gaseous PAHs and
      particle-bound PAHs) and dermal exposures have been assessed.

PMID- 12074033
TI  - Effect on blood lead of airborne lead particles characterized by size.
AB  - Worker exposure to airborne lead particles was evaluated for a total of 117
      workers in 12 work-places of four different industrial types in Korea. The
      particle sizes were measured using 8-stage cascade impactors worn by the workers.
      Mass median aerodynamic diameters (MMAD) were determined by type of industry and
      percentage of lead particles as a fraction of airborne lead (PbA) concentration
      was determined by particle size. Blood lead (PbB) levels of workers who matched
      airborne lead samples were also examined. A Scheffe's pairwise comparison test
      showed that MMAD and the fractions of each of respirable particles and lead
      particles < or =1 microm relative to PbA varied greatly by the type of industry.
      The concentrations of lead particles < or =1 microm, which the Center for Policy
      Alternatives model assumes is relatively constant at 12.5 microg/m3, increased
      with increasing PbA concentration. In addition, a better correlation was detected
      between concentrations of particles < or =1 microm and concentrations of
      respirable lead particles (r = 0.82) than that between concentrations of small
      particles and PbA (r = 0.61). A simple linear regression indicated that PbB
      correlated better with respirable lead concentration (r2 = 0.35, P = 0.0001) than
      with PbA concentration and had a higher slope coefficient. Controlling for
      respirable lead concentration reduced the partial correlation coefficient between
      PbA concentration and PbB level from 0.56 to 0.20 (P = 0.053). The results
      indicate that the contribution of respirable lead particles to lead absorption
      would be greater than that of PbA. This study concludes that the measurement of
      PbA only may not properly reflect a worker's exposure to lead particles with
      diverse characteristics. For the evaluation of a worker's exposure to various
      types of lead particles, it is recommended that respirable lead particles as well
      as PbA be measured.

PMID- 12074034
TI  - A quantitative approach for estimating exposure to pesticides in the Agricultural
      Health Study.
AB  - We developed a quantitative method to estimate long-term chemical-specific
      pesticide exposures in a large prospective cohort study of more than 58000
      pesticide applicators in North Carolina and Iowa. An enrollment questionnaire was
      administered to applicators to collect basic time- and intensity-related
      information on pesticide exposure such as mixing condition, duration and
      frequency of application, application methods and personal protective equipment
      used. In addition, a detailed take-home questionnaire was administered to collect
      further intensity-related exposure information such as maintenance or repair of
      mixing and application equipment, work practices and personal hygiene. More than
      40% of the enrolled applicators responded to this detailed take-home
      questionnaire. Two algorithms were developed to identify applicators' exposure
      scenarios using information from the enrollment and take-home questionnaires
      separately in the calculation of subject-specific intensity of exposure score to
      individual pesticides. The 'general algorithm' used four basic variables (i.e.
      mixing status, application method, equipment repair status and personal
      protective equipment use) from the enrollment questionnaire and measurement data
      from the published pesticide exposure literature to calculate estimated intensity
      of exposure to individual pesticides for each applicator. The 'detailed'
      algorithm was based on variables in the general algorithm plus additional
      exposure information from the take-home questionnaire, including types of mixing
      system used (i.e. enclosed or open), having a tractor with enclosed cab and/or
      charcoal filter, frequency of washing equipment after application, frequency of
      replacing old gloves, personal hygiene and changing clothes after a spill.
      Weighting factors applied in both algorithms were estimated using measurement
      data from the published pesticide exposure literature and professional judgment.
      For each study subject, chemical-specific lifetime cumulative pesticide exposure
      levels were derived by combining intensity of pesticide exposure as calculated by
      the two algorithms independently and duration/frequency of pesticide use from the
      questionnaire. Distributions of duration, intensity and cumulative exposure
      levels of 2,4-D and chlorpyrifos are presented by state, gender, age group and
      applicator type (i.e. farmer or commercial applicator) for the entire enrollment
      cohort and for the sub-cohort of applicators who responded to the take-home
      questionnaire. The distribution patterns of all basic exposure indices (i.e.
      intensity, duration and cumulative exposure to 2,4-D and chlorpyrifos) by state,
      gender, age and applicator type were almost identical in two study populations,
      indicating that the take-home questionnaire sub-cohort of applicators is
      representative of the entire cohort in terms of exposure.

PMID- 12074035
TI  - Efficiency of 22 online databases in the search for physicochemical,
      toxicological and ecotoxicological information on chemicals.
AB  - The objective of this study was to evaluate the efficiency of 22 free online
      databases that could be used for an exhaustive search of physicochemical,
      toxicological and/or ecotoxicological information about various chemicals. Twenty
      two databases with free access on the Internet were referenced. We then selected
      27 major physicochemical, toxicological and ecotoxicological criteria and 14
      compounds belonging to seven different chemical classes which were used to
      interrogate all the databases. Two indices were successively calculated to
      evaluate the efficiency with taking or not taking account of their
      specialization. More than 50% of the 22 databases 'knew' all of the 14 chemicals,
      but the quantity of information provided is very different from one to the other
      and most are poorly documented. Two categories clearly appear with specialized
      and non-specialized databases. The HSDB database is the most efficient general
      database to be searched first, because it is well documented for most of the 27
      criteria. However, some specialized databases (i.e. EXTOXNET, SOLVEDB, etc.) must
      be searched secondarily to find additional information.

PMID- 12074036
TI  - Effect of Cr(VI) exposure on sperm quality.

PMID- 12074037
TI  - Cardiovascular abnormalities in patients with a carcinoid syndrome.
AB  - BACKGROUND: Heart failure is an important reason for morbidity and mortality in
      patients with carcinoid. Carcinoid heart disease is caused by increased levels of
      circulating serotonin. Because carcinoids also produce catecholamines, we
      evaluated cardiovascular manifestations of autonomic dysfunction in patients with
      a carcinoid syndrome. METHODS: Twenty patients with a midgut carcinoid, who had a
      carcinoid syndrome with a median duration of 72 months, and markedly elevated
      urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion were studied. RESULTS: Ten
      patients had no symptoms of heart failure, i.e. New York Heart Association (NYHA)
      functional class I, 6 had class II, and 4 class III heart failure. Transthoracic
      echocardiography (TTE) showed right-sided valvular abnormalities in 13 of 19
      evaluable patients (mild n=8, severe n=5). Fourteen of the 20 patients (70%) had
      an elevated concentration of plasma N-terminal atrial natriuretic peptide (N
      ANP), which correlated with NYHA class, TTE abnormalities, and increased urinary
      metanephrine excretion. Heart rate variability (HRV) parameters, in particular
      those associated with increased sympathetic activity (low frequency power,
      p=0.002 versus healthy individuals), were impaired but were independent of NYHA
      class and TTE findings and correlated with urinary metanephrine excretion (r=
      0.49, p<0.05). CONCLUSION: In these 20 carcinoid patients with substantial
      secretory activity of the tumour, overt cardiac morphological changes were
      present in a minority of patients. However, N-ANP values and HRV profile were
      markedly abnormal, and related to enhanced urinary excretion of catecholamine and
      metabolites, suggesting autonomic derangement. These abnormalities possibly
      herald the development of more severe cardiac dysfunction and may be indicative
      of the need for preventive drug treatment.

PMID- 12074038
TI  - Failure patterns of combined modality treatment in lung cancer: the impact of
      staging.
AB  - BACKGROUND: Patients with locally advanced non-small cell lung cancer (NSCLC) may
      be treated with induction chemotherapy (IC) followed by surgery with curative
      intent. The impact of staging inaccuracies on the failure rate of this intensive
      combined modality treatment approach, i.e. non-curative chemotherapy and
      thoracotomy, requires further investigation. METHODS: The records of a cohort of
      38 consecutive NSCLC IIIA-N2 patients treated with IC followed by surgery were
      reviewed. RESULTS: The clinical course strongly suggested that the standard
      diagnostic algorithm failed to demonstrate stage IV disease in 34% of the cases.
      Surgery instigated by CT-based response criteria at restaging after chemotherapy
      proved to be irradical in 70% of cases. CONCLUSION: Our data confirm the
      limitations of the current work-up of patients with apparently locally advanced
      NSCLC. This applies to the selection of patients to be assigned to combined
      modality treatment as well as to the post-chemotherapy assessment of
      resectability. Improved (re)staging of these patients will enhance the efficiency
      of intervention trials and prevent patients from being exposed to intensive and
      toxic therapy from which they derive no benefit.

PMID- 12074039
TI  - Pneumatosis cystoides intestinalis, four cases of a rare disease.
AB  - Pneumatosis cystoides intestinalis (PCI) is a disease in which small gas-filled
      cysts appear in the intestinal wall. Four cases presented here demonstrate the
      diversity of the associated diseases. In two of the patients constipation
      probably played a role; in the third patient decreased colonic motility, elevated
      intestinal pressure and increased mucosal permeability in the context of
      enteritis treated with codeine was the underlying problem; in the fourth high
      protein feeding and bowel ischaemia was diagnosed. Various aetiologies are
      presented in the literature. There is no specific history and physical or
      laboratory findings do not help to diagnose PCI. Plain abdominal film,
      ultrasound, computer tomography, magnetic resonance imaging, barium contrast
      studies and/or endoscopy may be necessary for diagnosis. Therapy is based on
      enhancing partial oxygen pressure in the bowel wall. PCI usually runs a benign
      course.

PMID- 12074040
TI  - Life-threatening hypokalaemia and quadriparesis in a patient with
      ureterosigmoidostomy.
AB  - We report quadriparesis as a result of severe hypokalaemia and acidosis in a 50
      year-old man who had undergone ureterosigmoidostomy for bladder extrophy 48 years
      earlier. Aggressive suppletion with intravenous potassium and bicarbonate
      combined with potassium-sparing diuretics and ACE inhibitors resulted in complete
      restoration of the serum potassium and resolution of the neurological symptoms.
      The underlying mechanism as well as the treatment of hypokalaemia and
      hyperchloraemic metabolic acidosis after ureterosigmoidostomy are briefly
      discussed.

PMID- 12074041
TI  - Flaccid paresis due to distal renal tubular acidosis preceding systemic lupus
      erythematosus.
AB  - We report a 25-year-old woman presenting with a flaccid paresis due to severe
      hypokalaemia as a consequence of distal renal tubular acidosis (dRTA). Six years
      after presentation of dRTA, she developed overt symptoms of systemic lupus
      erythematosus (SLE). dRTA in SLE is often secondary to an interstitial nephritis.
      In contrast to other reports the dRTA did not resolve after treatment with
      prednisone in our patient. Nephrocalcinosis might be one of the causal factors in
      the persistence of dRTA.

PMID- 12074042
TI  - Selection for the internal medicine residency programme in the Leiden region.
AB  - BACKGROUND: The selection and the professional training for a resident in
      internal medicine requires a great investment of time, training effort and money.
      Drop-outs are therefore considered a failure of the selection procedure. To
      evaluate our selection model and outcome of the training programme, we determined
      the drop-out rate at the Leiden University Medical Centre with its affiliated
      hospitals. METHODS: Data were collected from all files that have been kept from
      1988 onwards of all internists trained and registered in Leiden. These files
      contained the application forms, the assessments of the trainers and references
      and the specifications of the programme. Also the first employment as board
      certified internist is registered. RESULTS: The drop-out percentage of the
      training programme was 8.5%. The drop-outs did not differ in study
      characteristics from those who successfully completed the programme. The reports
      from the training team members showed that the drop-outs were as suitable and
      motivated as the other candidates. During the training programme 8.5% of the
      residents moved to another university to complete their training as an internist.
      All board-certified internists who graduated at the Leiden University Medical
      Centre found a job. CONCLUSIONS: The efficacy of the selection procedure for
      trainee internists is more than 90%. There are no studies in the literature for a
      comparison of data.

PMID- 12074043
TI  - Statins and the stroke-cholesterol paradox.
AB  - Although strokes belong to the group of cardiovascular disorders, there is no
      clear association between LDL and/or HDL levels and 'stroke' as an entity.
      However, there is ample evidence that statins reduce stroke risk in selected
      patient groups such as survivors of myocardial infarction. This apparent paradox
      can be explained on the one hand by the heterogeneity of strokes as a group and
      on the other hand by the specific characteristics of statins. There are strong
      indications for a relationship between blood lipid profiles and types of stroke
      that have atherosclerosis as the underlying pathogenetic mechanism. Apart from
      their ability to reduce LDL levels significantly, statins have a number of other
      properties, which influence the process of atherosclerosis at various stages.
      Future and ongoing trials have to prove which patients at risk for stroke will
      benefit most from the preventive use of statins.

PMID- 12074044
TI  - Primary polyclonal human T lymphocytes targeted to carcino-embryonic antigens and
      neural cell adhesion molecule tumor antigens by CD3zeta-based chimeric immune
      receptors.
AB  - Antigen-specific T lymphocytes are attractive as potential anticancer agents. The
      generation of large numbers of antigen-specific T cells is possible through the
      use of gene therapy to express targeting receptors on the T lymphocyte. Activated
      T lymphocytes were transduced to express carcino-embryonic antigen or neural cell
      adhesion molecule targeted CD3zeta chimeric immune receptors. The chimeric
      receptors were expressed as homodimers and also as heterodimers with the native
      CD3zeta. T lymphocyte populations were expanded in the absence of selection for
      the modified cells and were shown to produce cytokines when cultured in the
      presence of immobilized purified protein antigen. These lymphocytes also
      responded by cytokine production and cytolytic activity when challenged with
      tumor-cell lines expressing the antigen recognized by the chimeric immune
      receptor. The cytolytic activity appears to be largely perforin mediated.
      Furthermore, soluble carcino-embryonic antigen did not interfere with the
      functional activity of the carcino-embryonic antigen-targeted lymphocytes. Long
      term (5-day) stimulation of the modified lymphocytes by protein antigen resulted
      in reduced viability similar to that induced by anti-CD3 antibodies alone.
      Viability was improved by a costimulatory signal indicating that such signals may
      be vital in the maintenance of long-term functional activity of receptor modified
      T lymphocytes.

PMID- 12074045
TI  - Evaluation of dendritic cell immunogenicity after activation and chemical
      fixation: a mixed lymphocyte reaction model.
AB  - Dendritic cells (DC) are central to the control of adaptive immunity. Their
      ability to activate antigen-specific T cells depends on their maturation state.
      Many microbial and inflammatory products have stimulated DC maturation. This in
      vitro study used assays of phenotype and function to examine the potential of
      bacillus Calmette-Guerin, muramyl dipeptide, and CpG-rich oligodeoxynucleotides
      to stimulate DC maturation. A chemical fixation method was developed to reliably
      assess the functional potential of stimulated DC within a mixed lymphocyte
      reaction model. Using this method, it was shown that bacillus Calmette-Guerin
      provides a maturation signal as effective as the prototype DC stimulant
      interleukin-1beta. Furthermore, weaker stimuli such as muramyl dipeptide and CpG
      rich oligodeoxynucleotides also are able to induce functional maturation of DC.
      Using chemical fixation, it was possible to generate stable DC in an immature or
      a mature state. These observations have importance for our understanding of the
      regulation of adaptive immunity and for the design of DC-based immunotherapeutic
      strategies.

PMID- 12074046
TI  - Unexpected induction of unresponsiveness by vaccination with transformed
      Salmonella typhimurium.
AB  - Rats vaccinated with attenuated Salmonella typhimurium transformed with a vector
      containing the v2 exon of CD44 (SL-v2) were not protected and developed thymic
      metastases at a high rate. This was surprising because there was evidence for
      concomitant induction of a CD44v2-specific helper and cytotoxic T-cell response.
      The inefficacy of vaccination was partly caused by tumor escape and tumor-induced
      immunosuppression. More important were the facts that (i) BSpl2v2 cells migrated
      from the intraperitoneal implantation site to the thymus and (ii) after
      vaccination with transformed attenuated Salmonella typhimurium, a small number of
      dendritic cells, which had transcribed the cDNA insert, were detected in the
      thymus. In the thymic environment, these v2 presenting dendritic cells, as well
      as the BSp12v2 tumor cells, supported tolerance induction. Thus, vaccination with
      tumor-associated differentiation antigens, which in many instances have induced
      antitumor response, may deteriorate survival time and rate if vaccination is
      accompanied by presentation of the antigen during intrathymic T-cell selection.

PMID- 12074047
TI  - Dendritic cells cultured in anti-CD40 antibody-immobilized plates elicit a highly
      efficient peptide-specific T-cell response.
AB  - The function of dendritic cells (DCs), antigen-presenting cells that can initiate
      and regulate cellular and humoral responses, is highly influenced by their level
      of maturation. Immature DCs may be harmful in anti-tumor immunotherapy, because
      they can induce immunotolerance rather than immunostimulation. In this study, the
      authors sought to determine the optimal culture conditions for obtaining fully
      mature DCs. When DCs were cultured in agonistic anti-CD40 monoclonal antibody
      immobilized plates, they showed a higher expression of the maturation marker CD83
      than DCs cultured without CD40 ligation or those cultured in medium supplemented
      with anti-CD40 monoclonal antibody. In addition, when interferon-gamma (IFN
      gamma) was added to the medium, additive up-regulation of CD83 expression was
      observed. These DCs treated with both maturation signals showed a higher
      secretion of interleukin-12. To evaluate the capacity of antigen presentation,
      specific cytotoxic T lymphocytes were generated using autologous DC pulsed with a
      human lymphocyte antigen-A24-restricted peptide epitope derived from
      carcinoembryonic antigen. Interferon-gamma-secreting CD8+ T cells were analyzed
      by flow cytometry using the cellular affinity matrix technology. Dendritic cells,
      matured with CD40 ligation and IFN-gamma, were more efficient at eliciting an
      antigen-specific T-cell response in vitro than DCs stimulated with anti-CD40
      monoclonal antibody or IFN-gamma alone. A cytotoxicity assay using
      carcinoembryonic antigen-expressing tumor cell lines also showed that DCs matured
      with both signals were more efficient at inducing cytotoxic T lymphocytes. These
      results demonstrate that DC culture in an anti-CD40 monoclonal antibody
      immobilized plate in medium supplemented with IFN-gamma has a positive impact on
      DC maturation and may be optimal for eliciting an antigen-specific T-cell
      response without the need for CD4+ T-helper epitopes.

PMID- 12074049
TI  - Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored
      by the Society for Biological Therapy.
AB  - The Society for Biological Therapy held a Workshop last fall devoted to immune
      monitoring for cancer immunotherapy trials. Participants included members of the
      academic and pharmaceutical communities as well as the National Cancer Institute
      and the Food and Drug Administration. Discussion focused on the relative merits
      and appropriate use of various immune monitoring tools. Six breakout groups dealt
      with assays of T-cell function, serologic and proliferation assays to assess B
      cell and T helper cell activity, and enzyme-linked immunospot assay, tetramer,
      cytokine flow cytometry, and reverse transcription polymerase chain reaction
      assays of T-cell immunity. General conclusions included: (1) future vaccine
      studies should be designed to determine whether T-cell dysfunction (tumor
      specific and nonspecific) correlated with clinical outcome; (2) tetramer-based
      assays yield quantitative but not functional data (3) enzyme-linked immunospot
      assays have the lowest limit of detection (4) cytokine flow cytometry have a
      higher limit of detection than enzyme-linked immunospot assay, but offer the
      advantages of speed and the ability to identify subsets of reactive cells; (5)
      antibody tests are simple and accurate and should be incorporated to a greater
      extent in monitoring plans; (6) proliferation assays are imprecise and should not
      be emphasized in future studies; (7) the reverse transcription polymerase chain
      reaction assay is a promising research approach that is not ready for widespread
      application; and (8)there is a critical need to validate these assays as
      surrogates for vaccine potency and clinical effect. Current data and opinion
      support the use of a functional assay like the enzyme-linked immunospot assay or
      cytokine flow cytometry in combination with a quantitative assay like tetramers
      for immune monitoring. At present, assays appear to be most useful as measures of
      vaccine potency. Careful immune monitoring in association with larger scale
      clinical trials ultimately may enable the correlation of monitoring results with
      clinical benefit.

PMID- 12074048
TI  - Response rates of patients with metastatic melanoma to high-dose intravenous
      interleukin-2 after prior exposure to alpha-interferon or low-dose interleukin-2.
AB  - We evaluated 567 patients with metastatic melanoma who were treated with high
      dose intravenous interleukin-2 (IL-2) to determine whether prior treatment with
      either alpha-interferon or low-dose IL-2 altered the rates of response to
      subsequent high-dose IL-2. Of the 567 patients treated, 46 patients had received
      low-dose IL-2 before, and 78 had received alpha-interferon before. The response
      rate for patients who had received IL-2 before compared with IL-2 naive patients
      was 15% versus 21% respectively (p = 0.39). The response rate for patients who
      had received alpha-interferon before compared with patients who had not was 13%
      versus 21% (p = 0.084). Therefore, prior low-dose IL-2 therapy does not appear to
      prevent a subsequent response to high-dose IL-2. There is a trend for patients
      who received alpha-interferon before to have a lower-response rate to subsequent
      high-dose IL-2, but the number of patients evaluated in this study is too small
      to definitively answer this question.

PMID- 12074050
TI  - High-yield actinorhodin production in fed-batch culture by a Streptomyces
      lividans strain overexpressing the pathway-specific activator gene actll-ORF4.
AB  - Streptomyces lividans 1,326 usually does not produce the red/blue colored
      polyketide actinorhodin in liquid culture even though it carries the entire
      actinorhodin biosynthesis gene cluster. The bacterium can be forced to produce
      this secondary metabolite by introducing actII-ORF4, the actinorhodin pathway
      specific activator gene from Streptomyces coelicolor, on a multicopy plasmid. The
      production of actinorhodin by such a strain has been optimized by medium and
      process manipulations in fed-batch cultures. With high-yield cultivation
      conditions, 5 g actinorhodin/l are produced during 7 days of cultivation; or
      approximately 0.1 g actinorhodin/g dry weight (DW)/day in the production phase.
      The yield in this phase is 0.15 Cmol actinorhodin/Cmol glucose, which is in the
      range of 25% to 40% of the maximum theoretical yield. This high-level production
      mineral medium is phosphate limited. In contrast, nitrogen limitation resulted in
      low-level production of actinorhodin and high production of a-ketoglutaric acid.
      Ammonium as nitrogen source was superior to nitrate supporting an almost three
      times higher actinorhodin yield as well as a two times higher specific production
      rate. The wild-type strain lacking the multicopy plasmid did not produce
      actinorhodin when cultivated under any of these conditions. This work examines
      the actinorhodin-producing potential of the strain, as well as the necessity to
      improve the culture conditions to fully utilize this potential. The
      overexpression of biosynthetic pathway-specific activator genes seems to be a
      rational first step in the design of secondary metabolite overproducing strains
      prior to alteration of primary metabolic pathways for redirection of metabolic
      fluxes.

PMID- 12074051
TI  - Characterization of a cell-associated inulosucrase from a novel source: a
      Leuconostoc citreum strain isolated from Pozol, a fermented corn beverage of
      Mayan origin.
AB  - A cell-associated fructosyltransferase was extracted from a novel source, a
      strain of Leuconostoc citreum isolated from Pozol, a Mexican traditional
      fermented corn beverage, where lactic microflora are partially responsible for
      the transformation process. The enzyme is associated with the cell wall. It was
      characterized both in its cell-associated insoluble form and after separation by
      urea treatment. The fructosyltransferase has a molecular mass of 170 kDa, the
      highest reported for this type of enzyme, and in its insoluble form is highly
      specific for polymer synthesis, with low fructose transferred to maltose and
      lactose added to the reaction medium (acceptor reactions). The synthesized
      polymer has an inulin-like structure with beta2-1 glycosidic linkages, as
      demonstrated by 13C nuclear magnetic resonance (NMR). Bacterial inulosucrases
      have only been reported in Streptococcus mutans.

PMID- 12074052
TI  - Molecular characterization and utilization of the CAK1 filamentous viruslike
      particle derived from Clostridium beijerinckii.
AB  - An examination of the replication origin and stability determinant associated
      with the CAK1 filamentous viruslike particle recovered from Clostridium
      beijerinckii NCIMB 6444 was carried out. Seven deletion derivatives, pCKE, pCEP1,
      pDT5, pCKP, pDTH102, pYL102E and pYL102, were constructed and transformed into C.
      beijerinckii NCIMB 8052. The successful transformation of pCKE, pDT5, pCKP,
      pDTH102, pYL102E and pYL102 into C. beijerinckii 8052, together with the
      corresponding recovery of single-stranded DNA from Escherichia coli indicated
      that the double- and single-stranded replication origins are located on a 0.4-kb
      CAK1 DNA fragment. Sequence analysis of the putative 0.4-kb replication origin
      region of CAK1 reveals a nick site containing 22 base pairs that has homology
      with plasmids pC194 and pUB110 and suggests the presence of a 2.0-kb DNA region
      involved in stability. The putative Rep protein of CAK1 contains three conserved
      motifs and three essential residues of the catalytic site in agreement with Rep
      proteins associated with the pC194 family. The utility of the developed CAK1
      derived phagemid designated pYL102E was evaluated by using it to examine
      heterologous expression of: (1) the manA gene derived from Thermoanaerobacterium
      polysaccharolyticum in E. coli and C. beijerinckii NCIMB 8052 and (2) the sol
      operon derived from Clostridium acetobutylicum DSM 792 in C. beijerinckii SA-2.

PMID- 12074053
TI  - Containment in industrial biotechnology within wastewater treatment plants.
AB  - Both physical and biological containment are considered to be essential parts in
      the risk analysis of industrial Good Industrial Large-Scale Practice (GILSP)
      processes using genetically modified organisms (GMOs). Biological containment of
      industrial microorganisms has become a more important issue since the
      introduction of recombinant DNA techniques. In the event of an accidental
      discharge in the production plant, a large amount of organisms could be released
      into the wastewater treatment (WWT) system. This WWT system should therefore be
      considered as a part of the containment. This study demonstrates both a
      hydrodynamic and a microbiological model for the containment aspects of
      industrial WWT plants. The models are verified by measurements using industrial
      hosts of GILSP GMOs at full scale. Both models describe the full-scale equipment
      accurately. The results are supplemented with microcosm studies on survival of
      GMOs in defined niches. It is shown that WWT plants can be considered as useful
      additional parts of the containment of microorganisms, in case of an accidental
      discharge. The effect of drainage of an enormous amount of microorganisms
      (several tons) through the WWT plant into the environment is shown to be
      comparable to the direct drainage of a small-scale fermenter. Microcosm
      experiments correlate well with the survival rates in the WWT and therefore can
      be of use to predict the behaviour of GMOs in this environment.

PMID- 12074054
TI  - Transformation and mineralization of benzo[a]pyrene by microbial cultures
      enriched on mixtures of three- and four-ring polycyclic aromatic hydrocarbons.
AB  - Microorganisms originating from a soil contaminated by low levels of polycyclic
      aromatic hydrocarbons (PAHs) were enriched with three- and four-ring PAHs as
      primary substrates in the presence of benzo[a]pyrene (BaP). Most enrichment
      cultures, isolated in the presence or absence of a sorptive matrix, significantly
      transformed BaP. Evidence of BaP mineralization was obtained with cultures
      enriched on phenanthrene and anthracene. Our findings supplement literature data
      suggesting the wide occurrence of microbial activity against BaP.

PMID- 12074055
TI  - Characterization of up-regulated proteases in an industrial recombinant
      Escherichia coli fermentation.
AB  - Proteolytic degradation of recombinant proteins is an industry-wide challenge in
      host organisms such as Escherichia coli. These proteases have been linked to
      stresses, such as the stringent and heat-shock responses. This study reports the
      dramatic up-regulation of protease activity in an industrial recombinant E. coli
      fermentation upon induction. The objective of this project was to detect and
      characterize up-regulated proteases due to recombinant AXOKINE overexpression
      upon IPTG induction. AXOKINE is a 22-kDa protein currently in clinical trials as
      a therapeutic for obesity associated with diabetes. AXOKINE was expressed in both
      the soluble and inclusion body fractions in E. coli. Sodium dodecyl sulfate
      gelatin-polyacrylamide gel electrophoresis (SDS-GPAGE) was used to analyze the up
      regulated protease activity. Western blot analysis showed degraded AXOKINE in
      both the soluble and insoluble fractions. Protease inhibitors were used to
      characterize the proteases. The proteases were ethylenediaminetetraacetic acid
      (EDTA) sensitive. The protease activity increased in the presence of phenyl
      methyl sulfonyl-fluoride (PMSF), a serine protease inhibitor. The incubation
      buffer composition was varied with respect to Mg2+ and ATP, and the protease
      activity was ATP independent and Mg2+ dependent. A two-dimensional
      electrophoresis technique was used to estimate the pI of the proteases to be
      between 2.9 and 4.0.

PMID- 12074056
TI  - Purification and characterization of a Galactomyces reessii hydratase that
      converts 3-methylcrotonic acid to 3-hydroxy-3-methylbutyric acid.
AB  - Cell free extracts of Galactomyces reessii contain a hydratase as the key enzyme
      for the transformation of 3-methylcrotonic acid to 3-hydroxy-3-methylbutyric
      acid. Highest levels of hydratase activity were obtained during growth on
      isovaleric acid. The enzyme, an enoyl CoA hydratase, was purified 147-fold by
      precipitation with ammonium sulphate and successive chromatography over columns
      of DE-52, Blue Sepharose CL-6B and Sephacryl S-200. During purification,
      hydratase activity was measured spectrophotometrically (OD change at 263 nm) for
      3-methylcrotonyl CoA and crotonyl CoA as substrates. The enzyme displayed highest
      activity with crotonyl CoA with a Kcat of 1,050,000 min(-1). The ratio of
      crotonyl CoA to 3-methylcrotonyl CoA activities was constant (20:1) during all
      steps of purification. The Kcat for crotonyl CoA was also about 20 times greater
      than the Kcat for 3-methylcrotonyl CoA (51,700 min(-1). The enzyme had pH and
      temperature optima at 7.0 and 35 degrees C, a native Mr of 260 +/- 4.5 kDa and a
      subunit Mr of 65 kDa, suggesting that the enzyme was a homotetramer. The pI of
      the purified hydratase was 5.5, and the N-terminal amino acid sequence was
      VPEGYAEDLLKGKMMRFFDS. Hydratase activity for 3-methylcrotonyl CoA was
      competitively inhibited by acetyl CoA, propionyl CoA and acetoacetyl CoA.

PMID- 12074057
TI  - Metabolite repression inhibits degradation of benzo[a]pyrene and
      dibenz[a,h]anthracene by Stenotrophomonas maltophilia VUN 10,003.
AB  - Large inocula of Stenotrophomonas maltophilia VUN 10,003 were used to investigate
      bacterial degradation of benzo[a]pyrene and dibenz[a,h]anthracene. Although
      strain VUN 10,003 was capable of degrading 10-15 mg (-1) of the five-ring
      compounds in the presence of pyrene after 63 days, further addition of pyrene
      after degradation of the five-ring polycyclic aromatic hydrocarbons (PAHs) ceased
      did not stimulate significant decreases in the concentration of benzo[a]pyrene or
      dibenz[a,h]anthracene. However, pyrene was degraded to undetectable levels 21
      days after its addition. The amount of benzo[a]pyrene and dibenz[a,h]anthracene
      degraded by strain VUN 10,003 was not affected by the initial concentration of
      the compounds when tested at 25-100 mg l(-1), by the accumulation of by-products
      from pyrene catabolism or a loss of ability by the cells to catabolise
      benzo[a]pyrene or dibenz[a,h]anthracene. Metabolite or by-product repression was
      suspected to be responsible for the inhibition: By-products from the degradation
      of the five-ring compounds inhibited their further degradation.

PMID- 12074058
TI  - Expression of an alpha-galactosidase from Saccharomyces cerevisiae in Aspergillus
      awamori and Aspergillus oryzae.
AB  - A gene encoding alpha-galactosidase activity was isolated by polymerase chain
      reaction (PCR) from Saccharomyces cerevisiae NCYC686 and separately placed under
      the control of transcriptional elements regulating alpha-amylase expression in
      Aspergillus oryzae and glucoamylase expression in A. awamori. Following
      transformation of both A. oryzae and A. awamori with their respective expression
      vectors, induction of heterologous alpha-galactosidase from positively selected
      clones was effected through the addition of soluble starch (10% wt/vol) to the
      growth medium. Upon induction in A. oryzae, a transcriptional instability
      resulted in degradation of mRNA encoding heterologous alpha-galactosidase, thus
      preventing expression of the active enzyme. The use of a gene fusion strategy in
      A. awamori overcame this instability and resulted in stable expression of S.
      cerevisiae alpha-galactosidase. Subsequent to initial (shake flask) experiments,
      a series of scale-up and optimisation studies led to heterologous expression of
      the recombinant enzyme in batch fermentation at 51 U mg(-1) total extracellular
      protein. This was higher than previously published works, which reported
      extracellular levels of heterologous alpha-galactosidase up to 38 U mg(-1) total
      protein. Analysis of crude extracts of the fermentation medium revealed
      significant differences between the activity parameters reported previously in
      the literature for this enzyme and those observed here. The recombinant enzyme
      exhibited thermostability properties not previously reported for S. cerevisiae
      alpha-galactosidase, a trait which would make it suitable for use in processes
      requiring high temperatures.

PMID- 12074059
TI  - Minimally invasive parathyroidectomy using the 'focused' lateral approach. I.
      Results of the first 100 consecutive cases.
AB  - BACKGROUND: A feasibility study of 'focused' minimally invasive parathyroidectomy
      (MIP) using a lateral approach was commenced in 1999. The aim of the present
      paper was to evaluate the effectiveness and safety of this procedure in the first
      100 consecutive patients. METHODS: This was a prospective, non-randomized case
      control study. One hundred consecutive patients with primary hyperparathyroidism
      (mean age 63.1 years; 74 females, 26 males) who fulfilled the inclusion criteria
      underwent focused MIP between May 1999 and December 2000. The results for the
      first and last 50 consecutive patients were compared to see whether they were
      reflective of a learning curve. The role of intraoperative quick parathyroid
      hormone (QPTH) estimation was also evaluated. RESULTS: Focused MIP was
      successfully completed in 93 of 100 patients, with seven conversions. Three
      (3.2%) of the 93 patients had persistent hyperparathyroidism. Quick PTH was
      measured in 81 patients and the results were true positive (for cure) in 72
      patients, false negative in six patients, true negative in two patients and false
      positive in one patient. Transient recurrent laryngeal nerve paresis occurred in
      one patient. During the same time period, open parathyroidectomy was performed in
      242 patients. The results were not different between the first and later 50
      patients undergoing MIP, nor were the outcomes significantly different from
      patients undergoing open parathyroidectomy. CONCLUSIONS: Focused MIP is a safe
      and effective operative approach for appropriately selected patients. Failed
      procedures were invariably related to shortcomings of the localization studies.
      Measurement of QPTH, although accurate, is unreliable in the presence of
      multigland disease.

PMID- 12074060
TI  - Assessment of myocardial injury by troponin T in off-pump coronary artery
      grafting and conventional coronary artery graft surgery.
AB  - PURPOSE: The present study was undertaken to assess the degree of myocardial
      injury, using troponin T (TnT), in off-pump coronary artery surgery (OPCAB) and
      in a comparable patient group undergoing conventional coronary artery graft
      surgery (CABG). METHODS: Twenty-seven OPCAB and 27 CABG patients were
      investigated. Blood samples for TnT were taken at intubation and at 12, 24 and 72
      h. Nine patients (five OPCAB, four CABG) underwent 2 h sampling for 12 h for the
      assessment of the TnT release profile. All patients had an electrocardiogram
      performed preoperatively and on the mornings of days 1 and 5 postoperatively.
      RESULTS: The OPCAB group had significantly greater Canadian Heart Classification
      3 patients (P = 0.003); however, other demographic data were similar between the
      two groups. All patients had normal TnT at initial sampling. The mean number of
      grafts in each group was 1.8 +/- 0.6 for OPCAB and 1.9 +/- 0.3 for CABG (P = NS).
      There were two new Q wave myocardial infarctions in the CABG group and none in
      the OPCAB group. These cases were excluded from biochemical analyses. Troponin T
      release was significantly less in the OPCAB group at 12 and 24 h (P < 0.001 and P
      = 0.03, respectively). Peak TnT release occurred at 6-8 h in both groups.
      Troponin T release was significantly lower in the OPCAB group at 2, 4, 6, 8, 10
      and 12 h (P = 0.01, P = 0.03, P = 0.02, P = 0.02, P = 0.03 and P = 0.04,
      respectively). Postoperatively, the OPCAB group required less blood transfusion
      (P = 0.02). CONCLUSIONS: The OPCAB group demonstrated a significantly reduced TnT
      release profile compared with the CABG group.

PMID- 12074061
TI  - Women's choice between sentinel lymph node biopsy and axillary clearance.
AB  - PURPOSE: To determine whether women would choose sentinel lymph node biopsy
      (SLNB) or axillary clearance (AC) for breast cancer treatment when they are given
      a single choice based on clear information about morbidity and mortality.
      METHODS: The expected 5-year survival rate of women with breast cancer after
      either SLNB or AC was calculated using a utility analysis of established
      literature. The difference in survival was one in 1000. This and other detailed
      information on SLNB and AC was presented in a questionnaire, which provided
      subjects with a scenario and a choice between SLNB and AC. After a pilot study of
      40 subjects, the questionnaire was mailed to 400 women (who had no mammographic
      abnormality) attending Breast Screen and handed to 100 women (who were over 40
      years of age and had breast symptoms but not cancer) attending the rooms of two
      surgical specialists. RESULTS: One hundred and twenty one of the 243 respondents
      to the mailed questionnaires (49.8%) chose SLNB and 35% of the 100 consulting
      room subjects chose SLNB rather than AC. CONCLUSIONS: Women faced with the
      possibility of having breast cancer seem to be very conservative in their choice
      of treatment, many choosing the increased morbidity of AC rather than the very
      small (one in 1000) increased risk of death at 5 years from SLNB. This raises
      questions about proposals to offer SLNB as standard treatment and demands that
      women are fully informed about any increased risk of death when making their
      choice between SLNB and AC.

PMID- 12074062
TI  - Malignancies of the external auditory canal and temporal bone: a review.
AB  - BACKGROUND: Malignancies of the external auditory canal and temporal bone are
      uncommon. A retrospective review was conducted of a large series treated at the
      Prince of Wales hospital between 1974 and 1995. METHODS: Retrospective review of
      59 cases of ear canal and temporal bone malignancies. These were analysed
      according to histopathology, disease extent, surgery, margin status and survival.
      A TNM-type staging system was applied to 51 cases and Kaplan-Meier survival
      analysis applied to this group. RESULTS: The 5-year cancer-specific survival
      (CSS) for the series was 54%. For stages 1, 2, 3 and 4 disease, the CSS were 90,
      45, 40 and 19%, respectively. Survival was significantly higher where clear
      surgical margins were achieved (80 vs 35%). CONCLUSIONS: Carcinoma of the
      external ear canal is rare and, in Australia, is often related to recurrence of
      periauricular cutaneous malignancy. Surgical extirpation with clear margins
      provides the best survival.

PMID- 12074064
TI  - How are we treating patients with hepatic colorectal metastases in Sydney?
AB  - INTRODUCTION: Colorectal cancer is common. At presentation 25% of patients have
      established hepatic metastases and overall at least half will develop hepatic
      metastases. Many different therapeutic options have been proposed. This study
      evaluates the current resources available and patterns of care for patients with
      hepatic colorectal metastases in the Sydney metropolitan area. METHODS:
      Prospective data were collated describing all patients presenting to any one of
      nine hospitals within the Sydney metropolitan area in a 12-month period,
      diagnosed with hepatic metastases. The data included patient demographics and
      background, treatment of the primary tumour, diagnosis and treatment of the
      hepatic metastases and histopathology both of the primary and of the hepatic
      metastases. RESULTS: There were 194 patients in the study. Most when diagnosed
      with hepatic colorectal metastases were independent, active, retired and usually
      had existing social supports. The majority had had their primary colorectal
      cancer resected and were later treated with systemic chemotherapy. CONCLUSIONS:
      This study highlights the need for a comprehensive multicentre, prospective data
      collection of patients with hepatic metastatic disease. This would clarify the
      effectiveness or otherwise of the health system caring for such patients and
      provide additional information for the development and implementation of
      guidelines.

PMID- 12074063
TI  - The submental artery island flap for head and neck reconstruction.
AB  - BACKGROUND: Following excisional surgery for head and neck cancer, most complex
      defects are reconstructed using microvascular free tissue transfer. These methods
      offer many advantages; however, they are of increasing complexity with attendant
      risks of flap loss and donor site problems. The submental artery island flap is a
      recently described local flap that may be used for reconstruction of the lower
      and middle thirds of the face and oral cavity, and offers the advantages of
      simplicity, reliability and excellent cosmesis. We have been using this flap as
      an alternative to free tissue transfer, and in this paper we present our series
      of 11 cases, after a review of the recent literature, anatomy and surgical
      technique. The advantages and limitations of the use of this flap are presented.
      METHODS: A consecutive series of 11 patients in which this reconstruction was
      performed was reviewed retrospectively, and the results studied. Advantages and
      disadvantages of this reconstructive method were determined to define appropriate
      indications and contra-indications for its use. RESULTS: We have used this flap
      in 11 patients for post-excisional soft tissue reconstruction of the head and
      neck, both as skin and as a mucosal replacement. In all but two patients the
      results were satisfactory, with excellent cosmesis when used as skin replacement.
      One patient required secondary debulking and one had complete flap loss. In all,
      the donor site was satisfactory. CONCLUSIONS: The Submenal Artery Island Flap is
      a useful addition to the reconstructive surgeon's options and has definite
      advantages over distant flaps in terms of ease of dissection, final cosmetic
      appearance and donor site appearance.

PMID- 12074065
TI  - Modern radiotherapy for modern surgeons: an update on radiation oncology.
AB  - Changes in the practice of radiation oncology have been significant over the last
      decade and continue to develop at an exciting rate. These advances range from our
      understanding of the increasingly important role of radiotherapy in the adjuvant
      and definitive settings to huge technological progress in the areas of tumour
      delineation, treatment planning, delivery and verification. In many cases,
      benefits have resulted from the ability of modern radiotherapy to deliver high
      doses with great accuracy and increasing safety in a highly individualized
      manner. This has impacted favourably on the management of all major malignancies
      as discussed in this paper. A good understanding of what can be achieved with
      modern radiotherapy has never been more important in ensuring an effective
      multidisciplinary approach to cancer management.

PMID- 12074066
TI  - Electrolysis and other local ablative treatments for non-resectable colorectal
      liver metastases.
AB  - The present paper is a review of the current ablative treatment options for the
      treatment of colorectal liver metastases. Cryotherapy, microwave coagulation
      therapy, radiofrequency ablation and laser-induced thermotherapy are discussed.
      Electrolysis, a novel non-thermal ablative treatment, is described. Potential
      benefits of electrolysis include the apparent ability to safely and effectively
      treat lesions abutting major hepatic structures and the lack of a systemic
      inflammatory reaction following electrolytic ablation. Further studies in animals
      and humans are needed to confirm this potential and to further refine the methods
      of electrolytic treatment of colorectal liver metastases.

PMID- 12074067
TI  - Is there a diminishing role for surgery for Merkel cell carcinoma of the skin? a
      review of current management.
AB  - Merkel cell carcinoma is a highly malignant skin tumour that must be managed in a
      multidisciplinary forum. Excisional biopsy of the primary is recommended and this
      should be followed by postoperative radiotherapy to the primary site, in-transit
      areas and the draining lymph nodes. The tumour is quite radiosensitive and
      radiation doses of the order of 50 Gy offer high levels of local control.
      Resection margins of 3 cm are not required provided postoperative radiotherapy is
      used. In the event of inoperable disease, patient refusal of surgery or a frail
      patient, radiotherapy should be used as the sole treatment modality, with high
      likelihood of achieving local control. Patients with involved nodes have a higher
      risk of distant disease. Traditionally, involved nodes have been managed with
      resection but, currently, there are protocols exploring the use of synchronous
      chemoradiotherapy as definitive treatment. Although adjuvant chemotherapy has
      been used in this setting to reduce the risk of distant seeding, the benefits at
      this stage have not been confirmed conclusively. The presence of distant disease
      carries a grave outlook and responses to chemotherapy occur frequently, but are
      usually shortlived.

PMID- 12074068
TI  - Minimally invasive parathyroidectomy using the 'focused' lateral approach. II.
      Surgical technique.
AB  - BACKGROUND: This paper describes the technique of minimally invasive
      parathyroidectomy. The technique is based on a thorough understanding of the
      anatomy of the fascial planes in neck, the surgical pathology and embryology of
      parathyroid glands and precise anatomical interpretation of preoperative
      localization studies. METHODS: Tissue trauma is minimized by using a 2.0 cm
      incision placed directly over the abnormal parathyroid gland and by removing the
      adenoma, without compromising the basic endocrine surgical principles of
      identification and preservation of recurrent laryngeal nerve, avoidance of any
      capsular breech, and ligation of the vascular pedicle. RESULTS/CONCLUSIONS: With
      proper patient selection, this technique results in a failure rate of less than
      4% and ensures that the incidence of complications, such as recurrent laryngeal
      nerve injury, remains comparable with that of standard open parathyroidectomy.

PMID- 12074069
TI  - Spontaneous splenic rupture secondary to metastatic gastric carcinoma: case
      report and review.

PMID- 12074070
TI  - Incisional hernia through iliac crest bone graft donor sites.

PMID- 12074071
TI  - Airway fire during formation of tracheostomy.

PMID- 12074072
TI  - Hydatid disease invading the inferior vena cava: successful combined medical and
      surgical treatment.

PMID- 12074073
TI  - Bouveret's syndrome in Melbourne.

PMID- 12074074
TI  - Laparoscopic bile duct injury: some myths.
AB  - Bile duct injury is a serious and feared complication of laparoscopic
      cholecystectomy. Examination of four frequently repeated statements about this
      problem in the literature, and in the medico-legal expert reports indicate that
      these statements are not supported by valid data and, therefore, can be termed
      'myths'.

PMID- 12074075
TI  - Osteoid osteoma in a young child: successful non-operative management.

PMID- 12074076
TI  - Acute appendicitis resulting from intraluminal shotgun pellets.

PMID- 12074078
TI  - Myths surrounding bile duct injury.

PMID- 12074077
TI  - Appendiced gunshot pellets.

PMID- 12074079
TI  - The evolving management of mechanical large bowel obstruction.

PMID- 12074080
TI  - Trade-offs: survival versus morbidity in breast cancer.

PMID- 12074081
TI  - Iatrogenic bile duct injury: the scourge of laparoscopic cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has become the first-line surgical
      treatment of calculous gall-bladder disease and the benefits over open
      cholecystectomy are well known. In the early years of LC, the higher rate of bile
      duct injuries compared with open cholecystectomy was believed to be due to the
      'learning curve' and would dissipate with increased experience. The purpose of
      the present paper was to review a tertiary referral unit's experience of bile
      duct injuries induced by LC. METHODS: A retrospective analysis was performed on
      all patients referred for management of an iatrogenic bile duct injury from 1981
      to 2000. For injuries sustained at LC, details of time between LC and recognition
      of the injury, time from injury to definitive repair, type of injury, use of
      intraoperative cholangiography (IOC), definitive repair and postoperative outcome
      were recorded. The type of injury sustained at open cholecystectomy was similarly
      classified to allow the severity of injury to be compared. RESULTS: There were
      131 patients referred for management of an iatrogenic bile duct injury that
      occurred at open cholecystectomy (n = 62), liver resection (n = 5) and at LC (n =
      64). Only 39% of bile duct injuries were recognized at the time of LC. Following
      conversion to open operation, half the subsequent procedures were considered
      inappropriate. When the injury was not recognized during LC, 70% of patients
      developed bile leak/peritonitis, almost half of whom were referred, whereas the
      rest underwent a variety of operative procedures by the referring surgeon. The
      remainder developed jaundice or abnormal liver function tests and cholangitis. An
      IOC was performed in 43% of cases, but failed to identify an injury in two-thirds
      of patients. The bile duct injuries that occurred at LC were of greater severity
      than with open cholecystectomy. Following definitive repair, there was one death
      (1.6%). Ninety-two per cent of patients had an uncomplicated recovery and there
      was one late stricture requiring surgical revision. CONCLUSIONS: The early
      prediction that the rate of injury during LC would decline substantially with
      increased experience has not been fulfilled. Bile duct injury that occurs at LC
      is of greater severity than with open cholecystectomy. Bile duct injury is
      recognized during LC in less than half the cases. Evidence is accruing that the
      use of cholangiography reduces the risk and severity of injury and, when
      correctly interpreted, increases the chance of recognition of bile duct injury
      during the procedure. Prevention is the key but, should an injury occur, referral
      to a specialist in biliary reconstructive surgery is indicated.

PMID- 12074082
TI  - Colonoscopy training: the need for patience (patients).
AB  - BACKGROUND: The insertion of a colonoscope to the caecum is a difficult technique
      to teach and to learn. The most commonly used criterion for proficiency is
      completion rate and early experience is often discouraging. In order to document
      the learning curve and better define normal progress for the early learning
      experience, the performance of trainees during their first 100-125 cases was
      recorded. METHODS: The completion rate and time for office colonoscopy were
      recorded prospectively over a 5-year period for each of 18 trainees. Trainees'
      experience was analysed in groups of 25 cases, numbered chronologically.
      Completion rate was defined as the number of examinations completed to the caecum
      by the trainee expressed as a percentage of the number completed by the staff.
      RESULTS: The mean overall completion rate for trainees was 56.4% (range 27.8
      83.9%). For the first five groups of 25 cases, the percentage completion rates
      (in order from first 25 cases to fifth 25 cases) were 43.1, 52.6, 49.3, 61.8 and
      75.1%, respectively. There was a wide variation in completion rates between
      trainees, but no difference in time taken. (Time for trainees to complete the
      procedure, in order from the first 25 cases to fifth 25 cases: 18.7, 19.1, 19.4,
      17.6 and 17.1 min, respectively.) CONCLUSIONS: Early experience in colonoscopy
      can be discouraging. At least 100 cases are needed to attain a level of
      proficiency that enables completion in two-thirds of cases, whereas 125 cases
      lead to an average completion rate of 75%.

PMID- 12074083
TI  - Total colectomy and J-pouch ileorectal anastomosis for obstructed tumours of the
      rectosigmoid junction.
AB  - BACKGROUND: Subtotal colectomy with ileosigmoid or ileorectal anastomosis is one
      of the standard procedures for obstructed tumours of the left colon. The lower
      the level of the anastomosis, the greater the number of bowel motions per day.
      The aim of the present study was to assess whether an ileal pouch-rectal
      anastomosis is associated with fewer bowel motions per day. METHODS: In four
      patients with obstructed carcinoma of the rectosigmoid junction and upper rectum,
      a total colectomy with removal of the upper rectum for adequate tumour clearance
      was used, followed by construction of a 10 cm ileal J-pouch that was subsequently
      anastomosed to the distal rectal stump. RESULTS: Postoperative recovery was
      uneventful in all patients. At 3 months postoperatively, anorectal manometry
      showed anal resting and squeeze pressures at lower normal limits and a neorectal
      capacity ranging from 160 to 310 mL. One year postoperatively, all patients
      experienced one to three normal bowel motions daily and no episodes of
      incontinence. CONCLUSIONS: Total colectomy with ileal J-pouch-rectal anastomosis
      is a reasonable operative alternative in cases with obstructed tumours of the
      rectosigmoid junction, which necessitate removal of the upper rectum.

PMID- 12074084
TI  - Combined endoscopic laser and radiotherapy palliation of advanced rectal cancer.
AB  - BACKGROUND: In the palliative treatment of patients with advanced, inoperable
      rectal cancer, combined endoscopic laser and radiotherapy have been claimed to be
      more effective than laser therapy alone. The number of laser treatments, laser
      energy used, relapse rate, treatment of relapse, morbidity and survival in
      consecutive patients who were treated either by laser therapy alone or laser plus
      radiotherapy was compared. METHODS: Prospective data were analysed with regard to
      number of treatments, laser energy used, relapse rate, morbidity and survival for
      56 consecutive patients. RESULTS: The crude relapse rate was significantly higher
      in the laser only group than in the laser plus radiotherapy group (58 and 15%,
      respectively; P = 0.002). There was no difference between the groups in the
      median total number of laser treatments or the mean total laser energy used. In
      patients experiencing a relapse, there was no difference in the median number of
      relapses, the number of laser treatments post-relapse or the total energy used
      post-relapse. Survival did not differ between the groups and there were no
      treatment-related deaths. CONCLUSIONS: These findings demonstrate a clear
      reduction in relapse after using combined laser and radiotherapy to palliate
      patients with advanced rectal cancer with no appreciable additional morbidity and
      have encouraged continuing use of this treatment.

PMID- 12074085
TI  - Application of metabolic engineering to improve both the production and use of
      biotech indigo.
AB  - A fermentation process was developed for production of indigo from glucose using
      recombinant Escherichia coli. This was achieved by modifying the tryptophan
      pathway to cause high-level indole production and adding the Pseudomonas putida
      genes encoding naphthalene dioxygenase (NDO). In comparison to a tryptophan-over
      producing strain, the first indigo-producing strain made less than half of the
      expected amount of indigo. Severe inactivation of the first enzyme of aromatic
      biosynthesis, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (the
      aroGfbr gene product), was observed in cells collected from indigo fermentations.
      Subsequent in vitro experiments revealed that DAHP synthase was inactivated by
      exposure to the spontaneous chemical conversion of indoxyl to indigo. Indigo
      production was thereafter improved by increasing the gene dosage of aroGfbr or by
      increasing substrate availability to DAHP synthase in vivo by either amplifying
      the tktA (transketolase) gene or inactivating both isozymes of pyruvate kinase.
      By combining all three strategies for enhancing DAHP formation in the cell, a 60%
      increase in indigo production was achieved. Metabolic engineering was then
      further applied to eliminate a byproduct of the spontaneous conversion of indoxyl
      to indigo, thereby solving a serious problem with the use of bio-indigo in the
      final denim dyeing application.

PMID- 12074087
TI  - Production technology for entomopathogenic nematodes and their bacterial
      symbionts.
AB  - Entomopathogenic nematodes (genera Steinernema and Heterorhabditis) kill insects
      with the aid of mutualistic bacteria. The nematode-bacteria complex is mass
      produced for use as biopesticides using in vivo or in vitro methods, i.e., solid
      or liquid fermentation. In vivo production (culture in live insect hosts) is low
      technology, has low startup costs, and resulting nematode quality is high, yet
      cost efficiency is low. In vitro solid culture, i.e., growing the nematodes and
      bacteria on crumbled polyurethane foam, offers an intermediate level of
      technology and costs. In vivo production and solid culture may be improved
      through innovations in mechanization and streamlining. In vitro liquid culture is
      the most cost-efficient production method but requires the largest startup
      capital and nematode quality may be reduced. Liquid culture may be improved
      through progress in media development, nematode recovery, and bioreactor design.
      A variety of formulations is available to facilitate nematode storage and
      application.

PMID- 12074086
TI  - The resistance to heat of thermo-resistant streptococci attached to stainless
      steel in the presence of milk.
AB  - Skim milk residues had a significant impact on the sensitivity to heat of a dairy
      isolate of the thermo-resistant, Streptococcus thermophilus. Cells of S.
      thermophilus (H) suspended in water or in milk had D values at 60 degrees C of
      2.0 and 14 min, respectively. Cells of S. thermophilus (H) attached to stainless
      steel in the presence of water or milk had D values at 60 degrees C of 2.2 and
      8.1 min, respectively. The attached cells in both experiments were heat-treated
      in the presence of water. The increase in heat resistance could not be fully
      attributed to individual components (caseinate or whey) in the milk. The
      potential for thermo-resistant streptococci to survive heat treatment in a dairy
      manufacturing plant is therefore greater than may be expected for the organism in
      less complex environments.

PMID- 12074089
TI  - Reduction of chromate by fixed films of sulfate-reducing bacteria using hydrogen
      as an electron source.
AB  - The ability of sulfate-reducing bacteria (SRB) to reduce chromate, Cr(VI), was
      evaluated using fixed-film growth systems and H2 as the electron source. A main
      objective of the experiment was to distinguish between direct enzymatic reduction
      and indirect reduction by hydrogen sulfide, in order to subsequently verify and
      control the synergy of these two mechanisms. In batch experiments with the
      sulfate-reducing consortium CH10 selected from a mining site, 50 mg l(-1) Cr(VI)
      was reduced in 15 min in the presence of 500 mg l(-1) hydrogen sulfide compared
      to 16 mg l(-1) reduced in 1 h without hydrogen sulfide. Fixed films of a CH10
      population and Desulfomicrobium norvegicum were fed-batch grown in a column
      bioreactor. After development of the biofilm, hydrogen sulfide was removed and
      the column was fed continuously with a 13-mg l(-1) Cr(VI) solution. Specific
      Cr(VI) reduction rates on pozzolana were close to 90 mg Cr(VI) h(-1) per gram of
      protein. Exposure to Cr(VI) had a negative effect on the subsequent ability of
      CH10 to reduce sulfate, but the inhibited bacteria remained viable.

PMID- 12074088
TI  - The synthesis of short- and medium-chain-length poly(hydroxyalkanoate) mixtures
      from glucose- or alkanoic acid-grown Pseudomonas oleovorans.
AB  - Pseudomonas oleovorans NRRL B-778 accumulated mixtures of poly-3-hydroxybutyrate
      (PHB) and medium-chain-length poly(hydroxyalkanoates) (mcl-PHAs) when grown on
      glucose, octanoic acid or oleic acid, whereas growth on nonanoic acid or
      undecanoic acid resulted in copolymers of poly-3-hydroxybutyrate-co-3
      hydroxyvalerate (PHB-co-HV). Acetone fractionation verified the presence of
      PHB/mcl-PHA mixtures. The acetone-insoluble (AIS) fractions of the polymers
      derived from glucose (PHA-glucose), octanoic acid (PHA-octanoic) and oleic acid
      (PHA-oleic) were exclusively PHB while the acetone-soluble (AS) fractions
      contained mcl-PHA composed of differing ratios of 3-hydroxy-acid monomer units,
      which ranged in chain length from 6 to 14 carbon atoms. In contrast, both the AIS
      and AS fractions from the polymers derived from nonanoic acid (PHA-nonanoic) and
      undecanoic acid (PHA-undecanoic) were composed of comparable ratios of 3
      hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV). The unfractionated PHA
      glucose, PHA-octanoic and PHA-oleic polymers had melting temperatures (Tm)
      between 177 and 179 degrees C, enthalpies of fusion (AHf) of 20 cal/g and
      glasstransition temperatures (Tg) of 3-4 degrees C. This was due to the large PHB
      content in the polymer mixtures. On the other hand, the PHA-nonanoic and PHA
      undecanoic polymers had thermal properties that supported their copolymer nature.
      In both cases, the Tm values were 161 degrees C, deltaHf values were 7 cal/g and
      Tg values were - 3 degrees C.

PMID- 12074090
TI  - Expression of tylM genes during tylosin production: phantom promoters and
      enigmatic translational coupling motifs.
AB  - In the genome of Streptomyces fradiae, the three tylM genes are codirectional
      with the upstream gene, tylGV. Although the introduction of transcriptional
      blocks into the tylM genes revealed that they are normally cotranscribed,
      expression of tylMI still persisted (albeit at a very low level) when either of
      the upstream genes, tylMII or tylMIII, was disrupted. Such expression apparently
      resulted from transcriptional initiation at spurious sites that probably
      contribute insignificantly, if at all, to promote activity in the wild type.
      Prior to the onset of tylosin production, tylMIII is transcribed independently of
      tylGV from an authentic promoter buried within tylGV. This latter observation is
      interesting given that the TGA stop codon of tylGV overlaps the GTG start codon
      of tylMIII. Evidently, terminally overlapping genes are not always
      translationally coupled.

PMID- 12074091
TI  - Influence of aromatic compounds on biodegradation of [14C]-labeled xylan and
      mannan by the white-rot fungus Phlebia radiata.
AB  - Radiolabeled [14C]arabinoxylan from wheat meal and [14C]galactoglucomannan from
      red clover meal were prepared by using 14CO2 as a precursor. Twice as much mannan
      was mineralized than xylan after 14 days of incubation with Phlebia radiata. Low
      molecular-weight phenolic compounds structurally related to lignin increased
      during mineralization of both hemicellulose fractions. Veratryl alcohol increased
      degradation of arabinoxylan by approximately 28.5%, whereas veratric acid
      increased it by only 9.0%. Vanillic acid and ferulic acid also stimulated
      degradation by 16.6% and 34.7%, respectively. Veratryl alcohol and ferulic acid
      increased degradation of galactoglucomannan by approximately 75%. Veratraldehyde
      in both cases repressed the degradation process (23.6% arabinoxylan, 43.8%
      galactoglucomannan). These results indicate that the degradation of
      hemicelluloses, e.g., xylan and mannan, by P. radiata is enhanced by addition of
      aromatic compounds.

PMID- 12074093
TI  - Microarray technology GEM microarrays and drug discovery.
AB  - Incyte Genomics' GEM Gene Expression Microarray is a proven genomics tool used by
      a large number of pharmaceutical companies to speed up the drug discovery and
      development process. The development and integration of this technology, together
      with Incyte's sequence databases and clone resources, have resulted in GEM
      microarrays that span approximately 60,000 human genes as well as approximately
      60,000 plant, rat, mouse, yeast, and bacterial genes. The technology underlying
      the use of these arrays and their application to the drug discovery process is
      highlighted.

PMID- 12074092
TI  - Enzymatic esterification of an acid with an epoxide using an immobilized lipase
      from Mucor miehei as catalyst: optimization of the yield and isomeric excess of
      ester by statistical analysis.
AB  - We have developed the methodology for the esterification of an acid with an
      epoxide using 2-chlorobutyric acid and 1,2-epoxy-5-hexene catalysed by a Mucor
      miehei-immobilized lipase. Thus, this methodology could be applied to obtain 2
      chloroesters. A factorial design of experiments and a central composite design
      have been used to optimise the synthesis of these esters. The variables chosen
      were temperature and initial catalyst concentration, while the responses were
      yield and isomeric excess of the ester. According to this study, temperature was
      the most important factor, having a positive influence on the yield and a small
      negative influence on the isomeric excess of the ester. The yield and isomeric
      excess of the ester show a greater dependence on temperature compared to the
      catalyst concentration. Although the effect of the catalyst concentration on both
      responses is smaller than the temperature effect, the higher selectivity
      presented by the biocatalyst towards the studied ester considerably decreased the
      final product distribution.

PMID- 12074094
TI  - The yeast lifecycle and DNA array technology.
AB  - The genome variability and meiotic gene expression patterns in two unrelated
      laboratory yeast strains, SK1 and W303, have been characterized using high
      density oligonucleotide arrays. The statistical analysis and comparison of the
      data has allowed identification of: (1) genes with functional importance to
      meiosis and sporulation in yeast and (2) genes expressed in a strain-specific
      manner. The genome-wide data also reveal potential reasons why these strains
      display significant differences in the ability to make fertile spores.
      Molecularly tagged yeast deletion strains have been used to determine the
      contribution of each gene to the execution of the sporulation/germination
      pathway. The application of genetics and the new genomic technologies have
      allowed a quantum jump in our understanding of yeast molecular biology.

PMID- 12074095
TI  - The protection of long chain polyunsaturated fatty acids by melatonin during
      nonenzymatic lipid peroxidation of rat liver microsomes.
AB  - The in vivo and in vitro effects of melatonin (N-acetyl-5-methoxytryptamine) on
      lipid peroxidation of long chain polyunsaturated fatty acids (PUFA) located in
      rat liver microsomes were determined. The effect of intraperitoneal
      administration of melatonin (10 mg/kg weight/24 hr) on ascorbate-Fe++ induced
      lipid peroxidation of isolated rat liver microsomes was first examined. The
      ascorbate induced light emission in hepatic microsomes was inhibited by melatonin
      treatment [control group: 10.714 +/- 0.894; melatonin group: 3.162 +/- 0.515,
      counts per minute (cpm) x 10(-5)]. Significant differences in the content of
      arachidonic C20:4 n-6 and docosahexaenoic acid C22:6 n-3 were observed when
      control microsomes were lipid peroxidized in the presence of ascorbic acid. These
      changes were less pronounced in liver microsomes isolated from melatonin treated
      rats. In vitro assays showed that after incubation of rat liver microsomes in an
      ascorbate-Fe++ system, at 37 degrees C for 210 min, the total cpm originated from
      light emission (chemiluminescence) was found to be lower in those membranes
      incubated in the presence of melatonin. The fatty acid composition of total
      lipids isolated from rat liver microsomes was substantially modified when
      subjected to nonenzymatic lipid peroxidation with a considerable decrease of
      docosahexaenoic acid 22:6 n-3 and arachidonic acid 20:4 n-6. The inhibition of
      the lipid peroxidation process evaluated as chemiluminescence (total cpm at
      selected times) was melatonin concentration dependent. Melatonin, at a
      concentration 1.2 mm, inhibited almost completely the lipid peroxidation process.
      Arachidonic and docosahexaenoic acids were more affected than docosapentaenoic
      acid during the lipid peroxidation process. Not all fatty acids were equally
      protected after the addition of melatonin to the incubation medium. Our results
      indicate that melatonin may act in vivo and in vitro as an antioxidant protecting
      long chain PUFA present in rat liver microsomes from the deleterious effect by a
      selective mechanism that reduces the loss of docosahexaenoic and arachidonic
      acids.

PMID- 12074097
TI  - Melatonin protects hepatic mitochondrial respiratory chain activity in senescence
      accelerated mice.
AB  - Mitochondrial oxidative damage from free radicals may be a factor underlying
      aging, and melatonin, a powerful free radical scavenger, may participate in
      mitochondrial metabolism. We measured respiratory chain complex I and IV
      activities in liver mitochondria from a strain of senescence-accelerated prone
      mice (SAMP8) and a strain of senescence-accelerated resistant mice (SAMR1) at age
      3, 6, and 12 months. No age-associated effects were found in either complex I and
      IV activities, thiobarbituric acid-reactive substances (TBARS), or glutathione
      peroxidase (GPx) activity in SAMRI. In contrast, SAMP8 showed significant age
      associated decreases in complex I and IV activities. While no age effect was
      found in TBARS in SAMP8, TBARS levels in SAMP8 were significantly more abundant
      than in SAMRI. GPx activity in SAMP8 decreased significantly by 12 months. Daily
      oral melatonin administration (2 microg/mL of drinking fluid) beginning when the
      mice were 7 months old significantly increased complex I and IV activity,
      decreased TBARS, and increased GPx activities in both SAMRI and SAMP8 at 12
      months. The implication of the findings is that melatonin may be beneficial
      during aging as it reduced the deteriorative oxidative changes in mitochondria
      and other portions of the cell associated with advanced age.

PMID- 12074096
TI  - The neuroprotective activities of melatonin against the Alzheimer beta-protein
      are not mediated by melatonin membrane receptors.
AB  - Exposure of neuronal cells to the Alzheimer's amyloid beta protein (Abeta)
      results in extensive oxidative damage of bio-molecules that are profoundly
      harmful to neuronal homeostasis. It has been demonstrated that melatonin protects
      neurons against Abeta-mediated neurotoxicity, including cell death and a spectrum
      of oxidative lesions. We undertook the current study to determine whether
      melatonin membrane receptors are involved in the mechanism of neuroprotection
      against Abeta neurotoxicity. For this purpose, we characterized the free-radical
      scavenging potency of several compounds exhibiting various affinities for
      melatonin membrane receptors (MLT 1a and 1b). Abeta-mediated neurotoxicity was
      assessed in human neuroblastoma cells and in primary hippocampal neurons. In
      sharp contrast with melatonin, no neuroprotection against Abeta toxicity was
      observed when we used melatonin membrane receptor agonists that were devoid of
      antioxidant activity. In contrast, the cells were fully protected in parallel
      control experiments when either melatonin, or the structurally unrelated free
      radical scavenger phenyl-N-t-butyl nitrone (PBN), were added to Abeta-containing
      culture media. This study demonstrates that the neuroprotective properties of
      melatonin against Abeta-mediated toxicity does not require binding of melatonin
      to a membrane receptor and is likely the result of the antioxidant and
      antiamyloidogenic features of the agent.

PMID- 12074098
TI  - Role of prostaglandins, nitric oxide, sensory nerves and gastrin in acceleration
      of ulcer healing by melatonin and its precursor, L-tryptophan.
AB  - Melatonin, a major hormone of pineal gland, was recently shown to attenuate acute
      gastric lesions induced by strong irritants because of the scavenging of free
      radicals but its role in ulcer healing has been little investigated. In this
      study we compared the effects of intragastric (i.g.) administration of melatonin
      and its precursor, L-tryptophan, with or without concurrent treatment with
      luzindole, a selective antagonist of melatonin MT2 receptors, on healing of
      chronic gastric ulcers induced by serosal application of acetic acid (ulcer area
      28 mm2). The involvement of endogenous prostaglandins (PG), nitric oxide (NO) and
      sensory nerves in ulcer healing action of melatonin and L-tryptophan was studied
      in rats treated with indomethacin and NG-nitro-L-arginine (L-NNA) to suppress,
      respectively, cyclo-oxygenases (COX) and NO synthases or in those with
      functionally deactivated sensory nerves with capsaicin. The influence of
      melatonin on gastric secretion during ulcer healing was tested in separate group
      of rats with gastric ulcer equipped with gastric fistulas (GF). At day 8 and 15
      upon the ulcer induction, the area of gastric ulcers was measured by planimetry,
      the mucosal blood flow (GBF) was determined by H2-gas clearance technique and
      gastric luminal NO2-/NO3- levels was assessed by Griess reaction. Plasma
      melatonin and gastrin levels were measured by specific radioimmunoassay (RIA).
      Biopsy mucosal samples were taken for expression of constitutive NO-synthase
      (cNOS) and inducible NOS (iNOS) by reverse transcriptase-polymerase chain
      reaction (RT-PCR). Melatonin (2.5-20 mg/kg-d i.g.) and L-tryptophan (25-100 mg/kg
      d i.g.) dose-dependently accelerated ulcer healing, the dose inhibiting by 50%
      (ED50) of ulcer area being 10 and 115 mg/kg, respectively. This inhibitory effect
      of melatonin (10 mg/kg-d i.g.) and L-tryptophan (100 mg/kg-d i.g.) on ulcer
      healing was accompanied by a significant rise in the GBF at ulcer margin and an
      increase of plasma melatonin. luminal NO2-/NO3- and plasma gastrin levels.
      Gastric acid and pepsin outputs were significantly inhibited during the ulcer
      healing in melatonin-treated gastric mucosa as compared with those in vehicle
      treated animals. Luzindole abolished completely the healing effects of melatonin
      and L-tryptophan and attenuated significantly the rise in plasma gastrin evoked
      by the hormone and its precursor. Indomethacin (5 mg/kg-d i.p). that blocked PG
      biosynthesis by 90% or L-NAME (20 mg/kg i.v), inhibitor of NOS. that suppressed
      luminal NO release, attenuated significantly melatonin and L-tryptophan-induced
      acceleration of ulcer healing and accompanying rise in GBF at ulcer margin and
      luminal NO release. The melatonin-induced acceleration of ulcer healing,
      hyperemia at ulcer margin and increase in the release of NO were enhanced when L
      arginine but not D-arginine was added to L-NAME. The ulcer healing and the GBF
      effects of melatonin and L-tryptophan were significantly impaired in rats with
      capsaicin-induced denervation of sensory nerves and both, ulcer healing and the
      hyperemia at ulcer margin were restored in these rats by addition of exogenous
      CGRP to melatonin and L-tryptophan. Expression of cNOS mRNA was detected by RT
      PCR in the intact gastric mucosa as well as at the edge of gastric ulcers treated
      with both, vehicle and melatonin, while iNOS mRNA that was undetectable in the
      intact gastric mucosa, appeared during ulcer healing and especially this was
      strongly up-regulated in the melatonin-treated gastric mucosa. We conclude that
      (1) exogenous melatonin and that derived from its precursor, L-tryptophan,
      accelerate ulcer healing probably via interaction with MT2 receptors; (2) this
      ulcer healing action is caused by an enhancement by melatonin of the
      microcirculation at the ulcer margin possibly mediated by COX-derived PG and NO
      because of overexpression of iNOS and (3) gastrin, which exhibits trophic
      activity in the gastric mucosa and calcitonin gene related peptide (CGRP),
      released from sensory nerves, may also contribute to the ulcer healing action of
      melatonin.

PMID- 12074099
TI  - Melatonin blocks rat hippocampal neuronal apoptosis induced by amyloid beta
      peptide 25-35.
AB  - To investigate whether melatonin protects neurons from apoptosis. we used amyloid
      beta-peptide 25-35 (Abeta(25-35)) to induce apoptosis in cultured hippocampal
      neurons, and monitored the apoptotic activity of the neurons with or without
      melatonin treatment. Present study shows that melatonin at concentrations of 1 x
      10(-6) and 1 x 10(-5) mol/L prevents neuronal morphological changes induced by
      apoptosis, as characterized by the shrunken and rounded morphology caused by
      condensed chromatin and fragmented DNA. Melatonin further exhibited the ability
      to inhibit apoptotic internucleosomal DNA degradation. Moreover, flow cytometric
      analysis of cell cycle demonstrated that melatonin abolished the Abeta(25-35)
      induced apoptotic peak. Our results suggest that melatonin may play an important
      role to protect neurons from Abeta(25-35)-induced apoptosis.

PMID- 12074100
TI  - Pretreatment with melatonin reduces volume of cerebral infarction in a rat middle
      cerebral artery occlusion stroke model.
AB  - Melatonin is a potent scavenger of free radicals and an indirect antioxidant.
      Recent studies have shown that melatonin possesses beneficial effects in
      experimental models of brain trauma and global cerebral ischemia. The effects of
      pretreatment with melatonin on volume of cerebral infarction were investigated in
      the present study. Adult male Sprague-Dawley rats were anesthetized with sodium
      pentobarbital to undergo right-sided endovascular middle cerebral artery
      occlusion (MCAO) for 3 hr. A single dose of melatonin (1.5, 5, 15, or 50 mg/kg in
      1 mL normal saline) or its vehicle was given via an intraperitoneal injection at
      0.5 hr before MCAO. Relative infarction volumes on day 3 after MCAO were
      significantly reduced in the groups treated with melatonin at 5 (mean +/- S.E.M.,
      15.7 +/- 2.5%) or 15 (21.4 +/- 3.1 %) mg/kg but not at 1.5 (30.6 +/- 3.5%) or 50
      (26.7 +/- 2.8%) mg/ kg when compared with the vehicle group (33.9 +/- 3.5%).
      There was no significant difference in the arterial blood pressure (BP), heart
      rate (HR) and relative cerebral blood flow among the experimental groups. These
      results indicate that pretreatment with melatonin at a dose between 5 and 15
      mg/kg protects against focal cerebral ischemia.

PMID- 12074101
TI  - Melatonin reduces memory changes and neural oxidative damage in mice treated with
      D-galactose.
AB  - To investigate the role of melatonin in D-galactose-induced amnesic mice, the
      avoidance/escape and water maze tests were performed to evaluate their learning
      and memory function. Spectrophotometry was employed to determine the content of
      thiobarbituric acid-reactive substances (TBARS) and the activities of
      antioxidative enzymes in the brain. The present results demonstrate that D
      galactose-induced amnesic mice had significantly decreased learning and memory
      function. The reduced activities of superoxide dismutase and glutathione
      peroxidase and increased levels of TBARS were found in brain tissue of the
      amnesic mice. Melatonin, administered (ig) at doses of 0.1, 1, or 10 mg/kg to the
      D-galactose-treated mice for 3 months, was sufficient to block these changes.
      These data suggest that D-galactose is involved in accelerating the brain aging
      process by elevating free radical generation and reducing antioxidative enzyme
      activities in vivo. Furthermore, the antioxidative activity of melatonin on the D
      galactose-treated mice may account for, at least partially, the improvement of
      learning and memory function in the aging and amnesic model.

PMID- 12074102
TI  - Long-term melatonin administration increases polyunsaturated fatty acid
      percentage in plasma lipids of hypercholesterolemic rats.
AB  - This study was designed to investigate the effect of melatonin on the fatty acid
      composition of plasma and tissue lipids. Melatonin administration to rats fed
      with a standard diet only increased long-chain n-6 polyunsaturated fatty acids
      (PUFA) in total plasma lipids and liver phospholipids but induced significant
      changes in hypercholesterolemic rats. In plasma, palmitoleic and oleic acids
      increased and n-6 and n-3 PUFA decreased in hypercholesterolemic rats; theses
      changes were reversed by melatonin administration. The analysis of lipid
      fractions revealed that only the cholesteryl ester fraction was affected by
      melatonin. Histological studies of the carotid artery intima revealed the
      appearance, in hypercholesterolemic rats, of fatty streaks produced by a mass of
      foam cells covered by the endothelium and by a thin layer of mononucleated cells.
      These changes were prevented by melatonin. We conclude that long-term melatonin
      administration modifies the fatty acid composition of rat plasma and liver lipids
      and ameliorates the arterial fatty infiltration induced by cholesterol.

PMID- 12074103
TI  - Protective effect of melatonin against cytotoxic actions of malondialdehyde: an
      in vitro study on human erythrocytes.
AB  - Malondialdehyde (MDA), a by-product of the oxidation of polyunsaturated fatty
      acids, is strongly cytotoxic. Here we report the in vitro ability of melatonin to
      protect intact human erythrocytes against the damage induced by the exposure to
      MDA. MDA at 20 microM caused marked variations in the red blood cell (RBC)
      membrane. High molecular weight fluorescent adducts were formed within minutes
      with membrane proteins. A 6-hr incubation led to the oxidation of membrane
      lipids, as reflected by the formation of conjugated diene (CD) lipid
      hydroperoxides and oxidation of vitamin E, and to an increase of the high
      molecular weight fluorescent adducts, which were an indication of MDA finally
      generated in the cells. Functional damage to the membrane was evident as a
      leakage of K+ ions into the incubation medium, and an increased resistance to
      osmotic lysis. A time-dependent hemolysis was observed by exposure of RBCs to 20
      microM MDA for 6-12 hr. Melatonin was not a substrate for MDA, therefore it was
      not able to prevent the early formation of the adducts from the reaction of the
      MDA in the medium with membrane proteins. Melatonin, however, concentration
      dependent prevented the formation of CD lipid hydroperoxides. As a consequence of
      counteracting the membrane lipid oxidation, the indoleamine prevented the loss of
      vitamin E and the increase of the fluorescent proteinaceous adducts observed
      after a 6-hr exposure to MDA. Melatonin also inhibited the K+ loss and returned
      to normal the osmotic resistance of the erythrocyte in the osmotic fragility
      test. By protecting membrane lipids and proteins, melatonin effectively prevented
      the MDA-induced time-dependent hemolysis. In the light of the known radical
      scavenging properties of melatonin, mechanisms of the cytoprotective effects of
      melatonin in our system are discussed.

PMID- 12074104
TI  - Effects of physiological and pharmacological concentrations of melatonin on
      ischemia-reperfusion arrhythmias in rats: can the incidence of sudden cardiac
      death be reduced?
AB  - Cardiac arrhythmias during ischemia-reperfusion (I/R) are believed to be related
      to free radicals generated in the heart especially during the period of
      reperfusion. The pineal secretory product, melatonin, is known to be a potent
      free radical scavenger and its pharmacological concentrations have been shown to
      reduce the I/R-induced arrhythmias in isolated rat hearts. However, the
      physiological role of melatonin in the prevention of these arrhythmias is
      unknown. Rats were pinealectomized (Px) or sham-operated (non-Px) (control) 2
      months before the I/R studies. To produce arrhythmias, left main coronary artery
      was occluded for 7 min, followed by 7 min reperfusion, in anesthetized rats. The
      incidence of mortality resulted from irreversible ventricular fibrillation (VF)
      was found significantly higher in the Px rats (63%) than in the control group
      (25%). Melatonin administration (0.4 mg/kg, either before ischemia or
      reperfusion) to Px rats significantly reduced the incidence of total
      (irreversible plus reversible) and irreversible VF and returned them to control
      values. On the other hand, melatonin administration (0.4 and 4 mg/kg) to non-Px
      rats failed to attenuate the I/R arrhythmias, significantly. These results
      suggest that physiological melatonin concentrations are important to reduce the
      I/R-induced VF and mortality, while pharmacological concentrations of melatonin
      did not increase its beneficial effect on these arrhythmias. As melatonin levels
      have been reported to decrease with age, melatonin replacement therapy may
      attenuate the incidence of sudden cardiac death especially in older patients.

PMID- 12074106
TI  - The case of the reluctant residents.

PMID- 12074105
TI  - Receptor-mediated modulation of avian caecal muscle contraction by melatonin:
      role of tyrosine protein kinase.
AB  - Abstract: Melatonin receptors in the quail caecum were studied by
      2[125I]iodomelatonin binding assay and the involvement of tyrosine protein kinase
      in the melatonin-induced contraction was explored. The binding of
      2[125I]iodomelatonin in the quail caecum membrane preparations was saturable,
      reversible and of high affinity with an equilibrium dissociation constant (Kd) of
      24.6 +/- 1.1 pm (n = 7) and a maximum number of binding sites (Bmax) of 1.95 +/-
      0.09 fmol (mg/protein) (n = 7). The relative order of potency of indoles in
      competing for 2[125I]iodomelatonin binding was: 2-iodomelatonin > melatonin > 2
      phenylmelatonin > 6-chloromelatonin > 6-hydroxymelatonin > N-acetylserotonin,
      indicating that ML(1) receptors are involved. The binding was inhibited by Mel1b
      melatonin receptor antagonists, luzindole and 4-phenyl-2-propionamidotetralin (4
      P-PDOT) as well as by non-hydrolyzable analogs of GTP like GTPgammaS and Gpp(NH)p
      but not by adenosine nucleotides. The latter suggests that the action of
      melatonin on the caecum is G-protein linked. Cumulative addition of melatonin (1
      300 nM) potentiated both the amplitude and frequency of spontaneous contractions
      in the quail caecum. The potentiation of rhythmic contractions was blocked by
      both luzindole and 4-P-PDOT. Antagonists of tyrosine kinase, genistein(2 microM)
      and erbstatin(4 microM) suppressed the modulation of spontaneous contractions by
      melatonin, but not inhibitors of protein kinase C (PKC) or protein kinase A
      (PKA). Melatonin-induced increment in spontaneous contraction was blocked by
      nifedipine (0.4 nM). Thus, we suggest that melatonin potentiates spontaneous
      contraction in the quail caecum via interacting with G-protein-coupled Mel(1b)
      receptor which may activate L-type Ca2+ channels by mobilizing tyrosine kinases.

PMID- 12074107
TI  - The pleasures of home birth?

PMID- 12074108
TI  - The pleasures of home birth?

PMID- 12074109
TI  - The pleasures of home birth?

PMID- 12074110
TI  - The pleasures of home birth?

PMID- 12074112
TI  - The pleasures of home birth?

PMID- 12074111
TI  - The pleasures of home birth?

PMID- 12074113
TI  - The pleasures of home birth?

PMID- 12074114
TI  - Politics at the CMA.

PMID- 12074115
TI  - Hippocrates reflect.

PMID- 12074116
TI  - Hippocrates reflect.

PMID- 12074117
TI  - Vitamin D insufficiency in a population of healthy western Canadians.
AB  - BACKGROUND: People with low levels of vitamin D and its metabolites are at
      increased risk for osteoporotic fractures. We wished to ascertain levels of
      vitamin D in a representative sample of adult western Canadians, to help assess
      the level of risk. We evaluated the prevalence of vitamin D insufficiency,
      defined as 25-hydroxyvitamin D [25(OH)D] less than 40 nmol/L, and seasonal
      variations in 25(OH)D, parathyroid hormone and related biochemical indices in a
      community-dwelling population of healthy Canadians living in Calgary (latitude 51
      degrees 07'N). METHODS: During calendar year 1999, we collected fasting overnight
      blood samples every 3 months from 60 men and 128 women (age range 27 to 89 years)
      who had volunteered to participate in another study. We used commercial
      radioimmunoassay kits to measure calciotrophic hormones and other biochemical
      indices. Regression models for longitudinal data were used to assess the effect
      of season and other potential predictors on individual parameters. RESULTS: For a
      total of 64 participants (34%), vitamin D insufficiency, defined as 25(OH)D less
      than 40 nmol/L, was recorded at least once out of the 4 sampling times. After
      adjustment for age, body mass index and holiday travel, we observed the
      anticipated rise in serum 25(OH)D from a mean of 57.3 (standard deviation [SD]
      21.3) nmol/L in the winter to 62.9 (SD 28.8) nmol/L in spring (p = 0.001) and
      71.6 (SD 23.6) nmol/L in summer (p < 0.001), with a subsequent decline to 52.9
      (SD 17.2) nmol/L in the fall (p = 0.008). The anticipated inverse relation
      between 25(OH)D and parathyroid hormone was not consistently observed: after
      adjustment for age, sex, body mass index and serum calcium, serum levels of
      parathyroid hormone did decrease significantly, from 39.5 (SD 18.8) ng/L in
      winter to 36.3 (SD 17.8) ng/L in summer (p = 0.001), but they continued to
      decline to 34.5 (SD 17.3) ng/L in the fall (p < 0.001). There was no association
      between 25(OH)D and parathyroid hormone (p = 0.21). INTERPRETATION: We documented
      a high prevalence of vitamin D insufficiency, which warrants consideration of
      dietary vitamin D supplementation.

PMID- 12074118
TI  - A qualitative study of evidence in primary care: what the practitioners are
      saying.
AB  - BACKGROUND: Little is known about the impact of evidence-based medicine in
      primary care. Our objective was to explore the influence of evidence on day-to
      day family practice, with specific reference to cardiovascular disease. METHODS:
      A total of 9 focus groups were conducted in rural, semi-urban and urban settings
      in Nova Scotia. The participants were 50 family physicians who had practised in
      their communities for more than 1 year and who were treating patients with
      cardiovascular disease. FINDINGS: Two major themes emerged: evidence in the
      clinical encounter and the culture of evidence. The family physicians reported
      thinking about evidence during the clinical encounter but still situated that
      evidence within the specific context of their patients and their communities.
      They appreciated evidence that had been appraised, summarized and published as a
      guideline by an independent national organization. Evidence remained in the
      forefront of consciousness for a limited time frame. Local specialists, trusted
      because of their previous successes with shared patient care, were important
      sources and interpreters of evidence. INTERPRETATION: Day-to-day family practice
      offers both obstacles and opportunities for the application of evidence. Although
      evidence is an important part of clinical practice, it is not absolute and is
      considered along with many other factors.

PMID- 12074119
TI  - Attitudes toward vaccination: a survey of Canadian chiropractic students.
AB  - BACKGROUND: Although the Canadian Chiropractic Association and the Canadian
      Memorial Chiropractic College (CMCC) endorse vaccination, the prevalence of anti
      vaccination attitudes among Canadian chiropractors is unknown. This study
      describes the prevalence of anti-vaccination attitudes among Canadian
      chiropractic students. METHODS: An 11-item questionnaire about attitudes toward
      vaccination was distributed to students enrolled at CMCC during the 1999/2000
      academic year. The responses for the 11 items were then summed to arrive at a
      total score ranging from 0 (most negative attitude toward vaccination) to 22
      (most positive attitude toward vaccination). Respondents' perceptions of sources
      of vaccine information were also investigated. RESULTS: Over 75% of the students
      (467 of 621) completed the questionnaire. Most students (53.3%) reported that in
      general they agreed with vaccination. This was especially true among first-year
      students (60.7%). However, among fourth year students, only 39.5% agreed with
      vaccination. The proportion of respondents who stated that they were against
      vaccination in general was 5 (4.5%) of 112 first-year students, 10 (8.3%) of 121
      second-year students, 16 (13.9%) of 115 third-year students and 35 (29.4%) of 119
      fourth-year students. The mean scores on the questionnaire were progressively
      lower with each higher year of study at the College. The mean survey scores for
      each year of study were first year, 15.9 (95% confidence interval [CI] 15.2
      16.6); second year, 16.1 (95% CI 15.3-1 7.0); third year, 14.5 (95% CI 13.5
      15.4); and fourth year, 12.8 (95% CI 11.7-13.9). The mean scores varied among
      year of study and were statistically significant using one-way ANOVA (p <
      0.0001). Among students who relied primarily on informal sources of vaccine
      information, such as the chiropractic literature and informal talks at CMCC, anti
      vaccination attitudes were more prevalent in later years. INTERPRETATION: Most
      CMCC students reported pro-vaccination attitudes, but there appeared to be an
      increase in anti-vaccination attitudes as students progressed through the CMCC
      program. This pattern was seen almost exclusively among students who relied
      primarily on informal sources of vaccine information rather than on core CMCC
      lectures or prior lectures at university.

PMID- 12074120
TI  - Prospective audit of the use of fresh-frozen plasma, based on Canadian Medical
      Association transfusion guidelines.

PMID- 12074121
TI  - Vitamin D insufficiency: no recommended dietary allowance exists for this
      nutrient.

PMID- 12074122
TI  - Bringing values into health care reform.

PMID- 12074123
TI  - Chiropractic students' attitudes about vaccination: a cause for concern?

PMID- 12074124
TI  - Identifying and managing adverse environmental health effects: 5. Persistent
      organic pollutants.
AB  - Concern and awareness is growing about the health effects of exposures to
      environmental contaminants, including those found in food. Most primary care
      physicians lack knowledge and training in the clinical recognition and management
      of the health effects of environmental exposures. We have found that the use of a
      simple history-taking tool - the CH2OPD2 mnemonic (Community, Home, Hobbies,
      Occupation, Personal habits, Diet and Drugs) - can help physicians identify
      patients at risk of such health effects. We present an illustrative case of a
      mother who is concerned about eating fish and wild game because her 7-year-old
      son has been found to have learning difficulties and she is planning another
      pregnancy. Potential exposures to persistent organic pollutants (POPs) and
      mercury are considered. The neurodevelopmental effects of POPs on the fetus are
      reviewed. We provide advice to limit a patient's exposure to these contaminants
      and discuss the relevance of these exposures to the learning difficulties of the
      7-year-old child and to the planning of future pregnancies.

PMID- 12074126
TI  - Unusual skin findings in a patient with liver disease.

PMID- 12074125
TI  - Clinical nutrition: 7. Functional foods--more than just nutrition.

PMID- 12074127
TI  - Hua Fo tablets tainted with sildenafil-like compound.

PMID- 12074128
TI  - Encouraging smoking cessation means fewer postoperative complications.

PMID- 12074129
TI  - Powdered infant formula and fatal infection with Enterobacter sakazakii.

PMID- 12074130
TI  - April the cruellest month for Canada's chiropractors.

PMID- 12074132
TI  - Health Canada targets postmarket surveillance of drugs.

PMID- 12074131
TI  - Vowing no more cheap labour, US residents file suit.

PMID- 12074133
TI  - BC trying to freeze costs in midst of a spending heat wave.

PMID- 12074134
TI  - Facing budget crunch, BC restructures health system.

PMID- 12074135
TI  - Women, heal thyself.

PMID- 12074136
TI  - Fully refocused gradient recalled echo (FRGRE): factors affecting flow and motion
      sensitivity in cardiac MRI.
AB  - The Fully Refocused Gradient Recalled Echo (FRGRE) magnetic resonance pulse
      sequence, previously reported as True FISP, was implemented and reported on a GE
      Signa CV/i 1.5T scanner. The purpose of this research was to optimize the pulse
      sequence design and scanning parameters to improve image quality for cardiac
      applications. A 2-D, multi-slice, multi-phase, breathold, segmented k-space,
      prospectively gated FRGRE sequence was implemented with TE and TR values as short
      as 0.9 and 3.0 msec, respectively. Pulse sequence design changes were
      investigated theoretically in terms of moment calculations and by assessing the
      quality of long- and short-axis cardiac images. The most influential scanning
      parameter for the improvement of image quality was both a short TR and TE.
      Placement of the z gradient rephaser immediately before the slice select gradient
      reduced the accumulated moments and improved image quality. Increasing the slice
      thickness from 3 to 8-10 mm significantly reduced flow artifact. The number of
      views per segment was doubled, without decreasing image quality, cutting
      breathold time in half compared to cardiac scanning with conventional sequences
      with longer TRs. The optimal flip angle was approximately 60 degrees. The use of
      a full or fractional echo had no noticeable effect on image quality.
      Surprisingly, the addition of flow compensation pulses significantly decreased
      image quality. In summary, optimization of sequence design and scanning
      parameters significantly reduced flow artifacts seen in FRGRE images.

PMID- 12074137
TI  - In vivo real-time intravascular MRI.
AB  - PURPOSE: The Magnetic resonance imaging (MRI) is an emerging technology for
      catheter-based imaging and interventions. Real-time MRI is a promising methodfor
      overcoming catheter and physiologic motion for intravascular imaging. METHODS:
      All imaging was performed on a 1.5 T Signa MRI scanner with high-speed gradients.
      Multiple catheter coils were designed and constructed, including low-profile,
      stub-matched coils. Coil sensitivity patterns and SNR measurements were compared.
      Real-time imaging was performed with an interleaved spiral sequence using a
      dedicated workstation, providing real-time data acquisition, image reconstruction
      and interactive control and display. Real-time "black-blood" imaging was achieved
      through incorporation of off-slice saturation pulses. The imaging sequence was
      tested in a continuous flow phantom and then in vivo in the rabbit aorta using a
      2 mm catheter coil. RESULTS: The real-time intravascular imaging sequence
      achieved 120-440 micron resolution at up to 16 frames per second. Low-profile
      stub-tuned catheter coils achieved similar SNR to larger traditional coil
      designs. In the phantom experiments, addition of real-time black-blood saturation
      pulses effectively suppressed the flow signal and allowed visualization of the
      phantom wall. In vivo experiments clearly showed real-time intravascular imaging
      of the rabbit aortic wall with minimal motion artifacts and effective blood
      signal suppression. CONCLUSIONS: Real-time imaging with low-profile coil designs
      provides significant enhancements to intravascular MRI.

PMID- 12074139
TI  - Effects of phase encode order and segment interpolation methods on the quality
      and accuracy of myocardial tags during assessment of left ventricular
      contraction.
AB  - Tissue tagging can be implemented during cardiovascular magnetic resonance
      imaging exams to assist with the quantification of left ventriculargeometry,
      volume and ejection fraction, endocardial thickening and relaxation, and
      myocardial stress-strain relationships. During tagged cine gradient echo image
      acquisitions of left ventricular wall motion, rows of k-space data can be
      acquired with various phase-encoding orders, and the reconstruction of
      supplemental images can be accomplished using a variety of interpolation
      techniques. In this study, we investigated the utility of various phase order and
      segment interpolation methods for determining accurate tag displacement
      trajectories. Center-out phase order image acquisition with reconstruction using
      linear interpolation provided the highest tag position and displacement accuracy.
      Therefore, it is recommended that myocardial tagging exams be acquired with
      center-out phase encode order and reconstructed using linear segment
      interpolation when used for performing quantitative analysis of cardiovascular
      structure and function.

PMID- 12074138
TI  - Temporal evolution of left ventricular strain late after repair of coarctation of
      the aorta using 3D MR tissue tagging.
AB  - PURPOSE: Following repair of coarctation of the aorta (CoA), LV mass is increased
      along with morbidity and mortality. Previous studies have reported increased
      shortening indices and impaired diastolic function. However, direct measurements
      of local material motion and temporal evolution of strain have been lacking.
      METHODS: Magnetic resonance (MR) tissue tagging was used to quantify regional
      three-dimensional myocardial deformation throughout systole and much of diastole
      in 14 patients (aged 19-23) who had CoA repair 17-23 years previously, and 15 age
      , sex- and BSA-matched normal volunteers (NV). RESULTS: Mass to end-diastolic
      volume ratio was increased in the CoA group (1.23 +/- 0.12 g/mL CoA vs. 1.14 +/-
      0.10 g/mL NV, p = 0.039), together with ejection fraction (65.3 +/- 4.4 vs. 60.8
      +/-1.9%, p = 0.001) and systolic blood pressure (132.5 +/- 14.5 vs. 117.3 +/-
      11.6 mmHg, p = 0.004). At end-systole, circumferential shortening was normal, but
      longitudinal shortening was decreased (14.9 +/- 1.3 vs. 16.8 +/- 1.4%, p <
      0.001). Although systolic strain rates were not significantly different, early
      diastolic strain rate (EDSR) in the CoA group was increased in the
      circumferential direction (-71 +/- 23 vs. -52 +/- 20%/sec, p = 0.029), but
      decreased in the longitudinal direction (-27 +/- 12 vs. -39 +/- 11%/sec, p =
      0.015). Longitudinal shortening and circumferential EDSR were related to right
      arm-leg pressure gradient (R2 = 0.20, p = 0.016 and R2 = 0.38, p < 0.001,
      respectively) and to mass index (R2 = 0.18, p = 0.024 and R2 = 014, p = 0.049,
      respectively). CONCLUSIONS: MR tagging allows quantitative information on the
      temporal evolution of myocardial deformation. Directionally dependent changes in
      strain evolution are seen late after CoA repair. These changes are related to
      both persistent arm-leg pressure gradient and degree of hypertrophy and may be
      indicators of developing dysfunction.

PMID- 12074140
TI  - Comparison of techniques for the measurement of left ventricular function
      following cardiac transplantation.
AB  - BACKGROUND: Assessment of graft function after cardiac transplantation is
      essential for patient management and clinical research. Previous studies have
      found that the left ventricular (LV) ejection fraction (EF) by echocardiography
      (echo), radionuclide ventriculography (RNV), and cardiovascular magnetic
      resonance (CMR) is discrepant in patients with heart failure. METHOD: Twelve
      patients underwent LV EF assessment by echo, angiography (angio), RNV, and CMR
      one year following heart transplantation. The scans were analyzed independently
      in blinded fashion. RESULTS: The mean EF was 63 +/- 6% by RNV, 66 +/- 6% by CMR,
      70 +/- 12% by angio, and 74 +/- 4% by echo. Significant differences were found
      between CMR and echo (p < 0.001), RNV and echo (p < 0.001), and RNV and angio (p
      < 0.05). The correlation between the techniques was poor (r = 0.3-0.6), and the
      scatter plots also suggested considerable variations between techniques. This was
      confirmed by the wide Bland-Altman limits of agreement (ranging from 22 to 45%).
      These were particularly wide for comparisons with angiography (43-45%).
      CONCLUSION: The EF measurement by echo, angio, RNV, and CMR are not
      interchangeable in patients following heart transplantation. The CMR and RNV
      provided the best agreement in EF and appear preferable for research studies.
      Echocardiography systematically overestimated LV EF and showed poor agreement
      with other techniques. Angiography overestimated LV function, and its routine use
      did not add to information gained from noninvasive studies.

PMID- 12074141
TI  - Respiratory maneuvers decrease irradiated cardiac volume in patients with left
      sided breast cancer.
AB  - Late cardiac morbidity and mortality among left breast cancer survivors treated
      with radiation therapy is related to cardiac volume included in the radiation
      portals. To determine if respiratory maneuvers can help decrease cardiac volume
      included in the radiation portals for left-sided breast cancer, 17 women with
      breast cancer, who had undergone left breast radiation therapy, underwent cardiac
      magnetic resonance imaging (MRI). Cardiac volume within the radiation portals was
      assessed from a transverse stack of eight, 10-mm thick, contiguous slices,
      covering the entire heart and obtained during breathholding at (1) endtidal
      volume (ETid) and (2) deep inspiration. Fourteen subjects (93% of those who
      completed the study) had inclusion of at least a portion of their heart within
      the radiation portals at ETid (median: 25.9 cm3, range 4.2-119.1 cm3). In all
      subjects, inspiratory breathholding decreased irradiated cardiac volume [median
      change: -18.1 cm3 (-49%), p < or = 0.001 vs. ETid]. In 21% of patients, the
      entire heart could be displaced outside the radiation field with deep
      inspiration. Age was not correlated with change or percentage change in cardiac
      volume with respiratory maneuvers. We conclude that in breast cancer patients,
      deep inspiratory maneuvers significantly decrease irradiated cardiac volume
      included in the left breast radiation field. Such an approach during delivery of
      radiation therapy allows preservation of radiation dosage to the breast, while
      reducing cardiac involvement and possible associated cardiovascular toxicity.

PMID- 12074142
TI  - Three-dimensional magnetic resonance coronary angiography using a new blood pool
      contrast agent: initial experience.
AB  - OBJECTIVE: The aim of this feasibility study was to assess the effect of a new
      blood pool contrast agent on magnetic resonance coronary angiography (MRCA) in
      patients suspected of having coronary artery disease. METHODS: Nine patients
      referred for diagnostic x-ray coronary angiography in the evaluation of chest
      pain underwent MRCA using a thin-slab three-dimensional (3D) breath-hold
      segmented gradient echo technique at 1.5 T before and after intravenous
      administration of feruglose, a new blood pool contrast agent. RESULTS: A total of
      36 coronary arteries, including 15 stenoses were evaluated. Overall agreement of
      visually assessed stenoses > 50% was 86%. The mean signal-to-noise ratio in the
      left anterior descending artery (LAD) did not change significantly after contrast
      administration, a relative improvement of 1.2 +/- 0.4 (p = 0.1), whereas the mean
      contrast-to-noise ratio of blood to myocardium improved by 3 +/- 2 (p = 0.01).
      CONCLUSION: A thin-slab 3D breath-hold scan combined with feruglose allows rapid
      localization and coverage of the proximal coronary arteries.

PMID- 12074143
TI  - Assessment of reactive hyperaemia using real time zonal echo-planar flow imaging.
AB  - The measurement of limb blood flow at rest and during reactive hyperaemia has
      potential as a marker of vascular health and endothelial function because it is
      the stimulus that causes flow-mediated dilatation, commonly measured as brachial
      arterial reactivity. Because the flow increases are short lived, they represent a
      significant challenge for measurement by cardiovascular magnetic resonance. In
      this study we used a real time, single shot zonal echo-planar imaging method
      (ZEPI) to study reactive hyperaemia in the femoral artery of five healthy
      volunteers. Flow velocity was measured every 78 msec. Changes in peak forward
      flow velocity during systole (580 vs. 390 mm/sec, p < 0.01) and minimum flow
      velocity (160 vs. 100 mm/sec, p < 0.01) were shown. With progressing improvement
      in spatial resolution, this technique will allow the accurate noninvasive
      determination of total flow, flow profile, and peak velocities in real time.

PMID- 12074144
TI  - Could cardiac magnetic resonance imaging replace cardiac ultrasound? Challenges
      from the echocardiography laboratory.

PMID- 12074145
TI  - Apical hypertrophic cardiomyopathy: clinical, electrocardiographic,
      scintigraphic, echocardiographic, and magnetic resonance imaging findings of a
      case.
AB  - The apical variant of nonobstructive hypertrophic cardiomyopathy (HCM)
      constitutes a minority of all cases of HCM and generally carries a favorable
      clinical outcome. We describe a 68 year-old Caucasian woman who presented with
      exertional dyspnea. The patient underwent stress testing with electrocardiogram
      gated single-photon emission computed tomography imaging and resting
      transthoracic echocardiography. The patient also underwent cardiac magnetic
      resonance imaging at rest, including conventional structural and functional
      imaging and cine complementary spatial modulation of magnetization-tagged imaging
      (CSPAMM). The noninvasive evaluation of the heart demonstrated apical hypertrophy
      with regional systolic dysfunction, establishing the diagnosis of apical HCM.
      This case suggests a potential value of CSPAMM in characterizing apical HCM.

PMID- 12074146
TI  - Cardiovascular magnetic resonance.

PMID- 12074147
TI  - RNase H and its effects on PCR.

PMID- 12074148
TI  - Automated high-throughput RNA analysis by capillary electrophoresis.

PMID- 12074149
TI  - Construction of expression vectors to produce affinity-tagged proteins in
      Pseudomonas.

PMID- 12074150
TI  - Synthesis of proteins with disulfide bonds in E. coli using defined culture
      media.

PMID- 12074151
TI  - Improved blunt-end cloning by replacing EcoRV with Eco32I.

PMID- 12074153
TI  - Amyloglucosidase suppresses interference by glycogen in the quantification of DNA
      using the Hoechst 33258 dye.

PMID- 12074152
TI  - Inhibition of bacterial pyridoxal-depending enzymes by (aminooxy)-acetic acid
      improves selective 15N isotope labeling of bacterially expressed protein.

PMID- 12074154
TI  - Microscale assay monitors algal growth characteristics.

PMID- 12074155
TI  - Dynamic imaging using fluorescence resonance energy transfer.

PMID- 12074156
TI  - One-step, highly efficient site-directed mutagenesis by toxic protein selection.
AB  - A fast and efficient site-directed mutagenesis method has been developed, using
      the newly constructed plasmid pTPS19, which expresses the toxic CcdB protein
      originally encoded by the E. coli F plasmid. Once the target gene is cloned into
      pTPS19, desired mutations can be introduced with two primers. The first contains
      the desired mutation, and the second is designed to create a +1 frame shift in
      the ccdB gene to inactivate the CcdB protein. The mutants can be directly
      selected on LB plates containing IPTG, through which the toxic CcdB protein is
      induced, thereby eliminating cells carrying wild-type parental plasmids. Based on
      stringent selection through the toxic CcdB protein, mutagenesis efficiency of 90%
      100% was reached even after one round of transformation.

PMID- 12074157
TI  - Minimal FLAG sequence useful in the functional epitope tagging of H-Ras.
AB  - Epitope tagging can interfere with normal protein function, indicating the need
      for an unobtrusive epitope tag. The FLAG epitope (DYKDDDDK) was examined for a
      minimal epitope useful in the tagging of H-Ras. The heptapeptide tag, F7
      (MDYKDDD), was found to retain reactivity with M2 and M5 monoclonal antibodies in
      immunoprecipitation, Western blotting, and immunofluorescence microscopy. The F7
      tag did not interfere with Ras stability, EGF stimulation of Ras activation, and
      downstream phosphorylation of MAPK Erk1/2. Unlike the full FLAG sequence, the F7
      tag had minimal effect on the growth properties of H-Ras in a colony-forming
      assay. The F7 tag may be useful when minimizing the effect of tagging on protein
      function is an important criterion in the selection of an N-terminal epitope tag.

PMID- 12074158
TI  - High-level expression of recombinant Fc chimeric proteins in suspension cultures
      of stably transfected J558L cells.
AB  - Recombinant Fc chimeric proteins are useful tools for studying protein function,
      including the analysis of molecular interactions by techniques such as expression
      cloning. Here we describe a method we have used to express the IgLON family
      proteins, CEPU1 and OBCAM, as recombinant Fc chimeric proteins in stably
      transfected mouse J558L myeloma cells. The use of this cell line provided the
      opportunity to maximize protein production, as it secretes antibodies in large
      quantities and can be grown to high density in small volumes of culture medium.
      Isolation of recombinant OBCAMFc from the adherent COS7 cell line suggested a
      minimum level of expression of 0.07 mg OBCAMFc/100 mL culture medium, while the
      J558L cell line expressed OBCAMFc at approximately 11.4 mg/100 mL culture medium.
      Purification of IgLON-Fc expressed by J558L cells was simpler than purification
      from COS7 cells because of the lower volume of culture medium generated.
      Furthermore, contamination of J558L expressed IgLONFc with bovine IgG from the
      culture medium was negligible. The method presented, which utilizes a
      commercially available small-scale bioreactor, provides the nonspecialist protein
      expression laboratory with the means to produce recombinant proteins quickly and
      easily in milligram quantities.

PMID- 12074159
TI  - Analysis of the activity of nuclear export signals using fluorescent BSA
      conjugates.
AB  - Here we demonstrate that fluorescein-labeled BSA conjugated with a mixture of
      nuclear import and export signals can be used to evaluate export activity. The
      method is based on the assumption that the intracellular distribution of the
      labeled conjugate [nuclear/cytoplasmic (N/C) fluorescent ratio] is dependent on
      the relative activity of the import versus the export signals. Using BALB/c cells
      as a model system, it was shown that this assumption is correct. Thus, the N/C
      fluorescent ratio increased significantly when an active leucine-rich nuclear
      export signal was replaced with its inactive mutant form in conjugates that also
      contained classical nuclear import signals. This approach was then used to
      demonstrate that the same leucine-rich nuclear export signal, which functions in
      vertebrates, is also active in amoebae.

PMID- 12074160
TI  - Magnetic bead purification of labeled DNA fragments for high-throughput capillary
      electrophoresis sequencing.
AB  - We have developed an automated purification method for dye-terminator-based DNA
      sequencing products using a magnetic bead approach. This 384-well protocol
      generates sequence fragments that are essentially free of template DNA, salt, and
      excess dye-terminator products. In comparison with traditional ethanol
      precipitation protocols, this method uses no centrifugation, is rapid, completely
      automated, and increases the phred-20 read length by an average of 40 bases. To
      date, we have processed over 4 million samples with 94% averaging 641 phred-20
      bases on the MegaBACE 1000 and 4000 and the ABI PRISM 3700 capillary instruments.

PMID- 12074162
TI  - Local mean normalization of microarray element signal intensities across an array
      surface: quality control and correction of spatially systematic artifacts.
AB  - Here we present a methodology for the normalization of element signal intensities
      to a mean intensity calculated locally across the surface of a DNA microarray.
      These methods allow the detection and/or correction of spatially systematic
      artifacts in microarray data. These include artifacts that can be introduced
      during the robotic printing, hybridization, washing, or imaging of microarrays.
      Using array element signal intensities alone, this local mean normalization
      process can correct for such artifacts because they vary across the surface of
      the array. The local mean normalization can be usedfor quality control and data
      correction purposes in the analysis of microarray data. These algorithms assume
      that array elements are not spatially ordered with regard to sequence or
      biological function and require that this spatial mapping is identical between
      the two sets of intensities to be compared. The tool described in this report was
      developed in the R statistical language and is freely available on the Internet
      as part of a larger gene expression analysis package. This Web implementation is
      interactive and user-friendly and allows the easy use of the local mean
      normalization tool described here, without programming expertise or downloading
      of additional software.

PMID- 12074161
TI  - Toward a universal standard: comparing two methods for standardizing spotted
      microarray data.
AB  - DNA microarray technology has allowed the transcriptome to be studied to a depth
      that was inconceivable only 10 years ago. Until recently these studies were
      isolated because, without a universal standard, the results from experiment to
      experiment and laboratory to laboratory were not directly comparable. For human
      microarrays, this problem has been addressed by numerous methods, but only two
      are truly universal. The first method uses genomic DNA as a standard for
      comparison since it is, by definition, complete and universally available. The
      second method employs a highly representative total RNA pool such as the one
      currently available from Stratagene. To determine the advantages and
      disadvantages of both methods, they were directly compared by hybridization to
      the University of Texas Southwestern Medical Center's 4000- or 10800-member human
      cDNA array, using typical microarray techniques. The labeled analytes were 2
      microg normal human genomic DNA labeled by nick translation or 20 microg total
      RNA pool labeled by reverse transcription. The resulting data were then
      background-subtracted, analyzed, and the number of spots above a background
      threshold was compared in each sample. Using the McNemar test and a Yate's
      correction with one degree of freedom, the samples were statistically identical
      with chi2 = 3.72.

PMID- 12074163
TI  - Creating arrays by centrifugation.
AB  - We describe afast, low-cost, and reliable way of creating arrays from sample
      molecules of interest present within microformatted sample vessels (such as 1536
      well microplates). The principle involves simple centrifugal transfer of
      molecules of interest onto a solid planar or membrane surfaces placed over the
      initial sample vessel. Tools and procedures are presented that validate the
      robustness and precision of this facile solution to an otherwise difficult
      problem in modern molecular genetics. The availability of transferred DNA
      molecules for hybridization is also demonstrated. In conclusion, this
      "centrifugal-array" concept should help research studies to be applied on ever
      greater scales with very simple machinery.

PMID- 12074164
TI  - RNA amplification results in reproducible microarray data with slight ratio bias.
AB  - Microarray expression analysis demands large amounts of RNA that are often not
      available. RNA amplification techniques have been developed to overcome this
      prcblem, but limited data are available regarding the reproducibility and
      maintenance of original transcript ratios. We optimized and validated two
      amplification techniques: a modified in vitro transcription for the linear
      amplification of 3 microg total RNA and a SMART PCR-based technique for the
      exponential amplification of 50 ng total RNA. To determine bias between
      transcript ratios, we compared the expression profiles in mouse testis versus
      spleen between the two amplification methods and a standard labeling protocol,
      using microarrays containing 4596 cDNAs spotted in duplicate. With each method,
      replicate hybridizations were highly reproducible. However, when comparing the
      amplification methods to standard labeling, correlation coefficients were lower.
      Twelve genes that exhibited inconsistent or contradictory expression ratios among
      the three methods were verified by quantitative RT-PCR. The amplification methods
      showed slightly more discrepancies in the expression ratios when compared to
      quantitative RT-PCR results but were more sensitive in terms of detecting
      expressed genes. In conclusion, although amplification methods introduce slight
      changes in the transcript ratios compared to standard labeling, they are highly
      reproducible. For small sample size, in vitro transcription is the preferred
      method, but one should never combine different labeling strategies within a
      single study.

PMID- 12074165
TI  - Conditions to ensure competitive hybridization in two-color microarray: a
      theoretical and experimental analysis.
AB  - We derived a theoretical model that explains certain biases observed in the two
      color microarray hybridization experiments reported in the literature. We show
      that true competition is achieved only when the hybridization kinetics of the two
      differentially labeled probes are the same. If the hybridization kinetics of the
      two differentially labeled probes is different, which can occur when the labeling
      and hybridization conditions for the two probes are dissimilar, then differential
      expression observed becomes a function of the amount of the target (i.e., DNA
      spotted on the slide). We use this model to validate the microarray methodology
      by determining the differential expression of four select Arabidopsis genes and
      two human genes (beta-actin and GAPDH) as a function of the amount of target
      arrayed. We show through both modeling and experiments that the rate constants
      for Cy5- and Cy3-labeled probes are the same under our exrimental conditions.
      Therefore, the target concentrations need not greatly exceed the probe
      concentration. It is obvious from the data presented that a simple treatment of
      an individual hybridization rate calculation does notfully describe what is
      occuring in today's complex, multispecies experiments. The method of validation
      is easily implemented to ensure data reliability by two-color microarray.

PMID- 12074166
TI  - Monitoring of representational difference analysis subtraction procedures by
      global microarrays.
AB  - Various approaches to the study of differential gene expression are applied to
      compare cell lines and tissue samples in a wide range of biological contexts. The
      compromise between focusing on only the important genes in certain cellular
      processes and achieving a complete picture is critical for the selection of
      strategy. We demonstrate how global microarray technology can be used for the
      exploration of the differentially expressed genes extracted through
      representational difference analysis (RDA). The subtraction of ubiquitous gene
      fragments from the two samples was demonstrated using cDNA microarrays including
      more than 32 000 spotted, PCR-amplified human clones. Hybridizations indicated
      the expression of 9100 of the microarray elements in a macrophage/foam cell
      atherosclerosis model system, of which many were removed during the RDA process.
      The stepwise subtraction procedure was demonstrated to yield an efficient
      enrichment of gene fragments overrepresented in either sample (18% in the
      representations, 86% after the first subtraction, and 88% after the second
      subtraction), many of which were impossible to detect in the starting material.
      Interestingly, the method allowed for the observation of the differential
      expression of several members of the low-abundant nuclear receptor gene family.
      We also observed a certain background level in the difference products of
      nondifferentially expressed gene fragments, warranting a verification strategy
      for selected candidate genes. The differential expression of several genes was
      verified by real-time PCR.

PMID- 12074167
TI  - High-throughput array production using precision glass syringes.
AB  - The advantages of using 1, 96, or 384 precision glass syringes in automated high
      throughput microdispensers in creating highly uniform and reproducible DNA,
      protein, and organic compound array filters and slides are described. Using the
      Hydra Microdispenser and Tango Liquid Handling system, 0.1-5 ng (in 50-300 nL)
      PCR-amplified, human cancer-related genes and housekeeping genes were spotted
      onto nylon membranes and coated slides. Protein solutions of 50 microg/mL to 1
      mg/mL were spotted onto coated slides or onto MaxiSorp 96-well plates. Up to 6144
      spots/membrane and up to 1000 spots/slide were printed. The size of the spots
      created by glass syringes was uniform and reproducible (precision variation of
      less than 5%) from spot to spot and membrane to membrane. Using a Tango 384
      system, a total of ten 6144-spot filters can be produced in approximately 25 min,
      translating into a spotting speed of 2.5 min/membrane.

PMID- 12074168
TI  - Loader Lite: a new software tool for the ABI PRISM 3700 DNA sequencer.
AB  - Here we describe the development of a novel software tool entitled Loader Lite
      that generates plate records or sample sheetsfor the ABI PRISMs 3700 DNA
      sequencer. The major advantage of this program is that it enables the ongoing
      operation of sequencing instruments without reference to external network(s). The
      autonomous operation of sequencing instruments is critical if sample throughput
      is to be maintained during periods of network outage. Loader Lite employs a
      deliberate strategy of inputting anonymous tray barcodes at run time. After
      sequencing, the barcodes are reconciled with relevant project details by
      reference to a database. This software takes advantage of barcode scanning
      technology by creating plate records directly on the local computer, serving an
      individual sequencer, immediately before importing and linking. This real-time
      synthesis of the plate records at the point of loading all but eliminates loading
      errors. Loader Lite is user-friendly, fully configurable, and permits the running
      of partial or full 384-well sample trays, using any standard combinations of run
      modules, dye sets, mobility files, analysis modules, etc. The 96-well format is
      not supported; however, this capability will appear in subsequent versions that
      are currently under development. This application is designed as an added value,
      adjunct program to the regular ABI PRISM 3700 Data Collection software. We have
      successfully used Loader Lite over the past six months to load approximately 7
      million sequencing reactions and believe its utility and functionality will prove
      to be attractive to the wider sequencing community.

PMID- 12074169
TI  - Processing of gene expression data generated by quantitative real-time RT-PCR.
AB  - Quantitative real-time PCR represents a highly sensitive and powerful technique
      for the quantitation of nucleic acids. It has a tremendous potential for the high
      throughput analysis of gene expression in research and routine diagnostics.
      However, the major hurdle is not the practical performance of the experiments
      themselves but rather the efficient evaluation and the mathematical and
      statistical analysis of the enormous amount of data gained by this technology, as
      these functions are not included in the software provided by the manufacturers of
      the detection systems. In this work, we focus on the mathematical evaluation and
      analysis of the data generated by quantitative real-time PCR, the calculation of
      the final results, the propagation of experimental variation of the measured
      values to the final results, and the statistical analysis. We developed a
      Microsoft Excel-based software application coded in Visual Basic for
      Applications, called Q-Gene, which addresses these points. Q-Gene manages and
      expedites the planning, performance, and evaluation of quantitative real-time PCR
      experiments, as well as the mathematical and statistical analysis, storage, and
      graphical presentation of the data. The Q-Gene software application is a tool to
      cope with complex quantitative real-time PCR experiments at a high-throughput
      scale and considerably expedites and rationalizes the experimental setup, data
      analysis, and data management while ensuring highest reproducibility.

PMID- 12074170
TI  - Computing fuzzy associations for the analysis of biological literature.
AB  - The increase of information in biology makes it difficult for researchers in any
      field to keep current with the literature. The MEDLINE database of scientific
      abstracts can be quickly scanned using electronic mechanisms. Potentially
      interesting abstracts can be selected by matching words joined by Boolean
      operators. However this means of selecting documents is not optimal. Nonspecific
      queries have to be effected, resulting in large numbers of irrelevant abstracts
      that have to be manually scanned To facilitate this analysis, we have developed a
      system that compiles a summary of subjects and related documents on the results
      of a MEDLINE query. For this, we have applied a fuzzy binary relation formalism
      that deduces relations between words present in a set of abstracts preprocessed
      with a standard grammatical tagger. Those relations are used to derive ensembles
      of related words and their associated subsets of abstracts. The algorithm can be
      used publicly at http:// www.bork.embl-heidelberg.de/xplormed/.

PMID- 12074171
TI  - Automatic quantitation of hybridization signals on cDNA arrays.
AB  - Large-scale hybridization of simple or complex cDNA probes to cDNA clones arrayed
      on high-density filters is a method frequently used to determine systematically
      the expression profiles of thousands of genes. Hybridization signal intensities,
      which reflect the level of transcription of the corresponding genes, are captured
      on phosphor screens with an imaging system. We describe a high-throughput system,
      Xdots-Reader, that performs automatic detection and quantitation of each signal
      on hundreds of images. Reproducibility of spot detection and quantitation within
      filters and between filters has been assessed in analysis of more than 850000
      hybridization signals on 436 filters. The automatic analysis success was greater
      than 97%, with 424 of the 436 tested filters fully analyzed without any human
      intervention. XdotsReader is available from the Software Library at
      www.BioTechniques.com or at http://www. ami. univ-evry. fr/approximately
      tahi/XDotsReader. It runs on SUN workstations under UNIX (SunOS or Solaris) and
      on PC under LINUX. No particular hardware is required, and the software is
      compatible with any other software. It supports the main standard image formats.

PMID- 12074172
TI  - Microarray Assistant clone organizer and array simulator.
AB  - Microarrays are extensively used in molecular biology experiments. While several
      vendors offer microarrays on a variety of platforms, many researchers prefer to
      use custom microarrays with a selected list of clones for their experiments. Many
      research centers have established core facilities for the production of custom
      microarrays. Microarray production involves a number of steps, including
      maintaining a master list of stock clones, selecting required clones for custom
      microarrays, subculturing selected clones, amplifying inserts, recording results,
      and identifying the orientation of clones in the microarray. We have created a
      simple, user-friendly, and versatile Microsoft Excel spreadsheet-based software,
      Microarray Assistant, which can assist the user in all the steps of microarray
      design and synthesis. In addition, the program gives options to insert, delete,
      or interchange clones during various steps. The program also gives a visual
      picture of the locations of the clones in the plates, as well as in the
      microarray. The program can also be used to assist in the transfer of clones
      between plates of different configuration.

PMID- 12074173
TI  - Use of degenerate primers and touchdown PCR for construction of cDNA libraries.
AB  - Optimized construction of low-redundancy cDNA mini-libraries using low-stringency
      RT-PCR is described cDNAs are generated using arbitrary consensus-degenerate
      hybrid oligonucleotide primers and nanogram amounts of Schistosoma mansoni mRNA.
      A number of conditions such as temperature and salt concentration are combined to
      create balanced, low-stringency conditions that permit a normalized amplification
      of a diversified, random set of sequences. On average, 350 different sequences
      are obtained per mini-library, which represents a significantly higher diversity
      of messages per library when compared to previously published conditions (ie., 20
      40 sequences/ mini-library). The optimized high-throughput approach described
      here is likely to help in the discovery of expressed genes in any complex
      organism.

PMID- 12074174
TI  - Persistent DNA contamination in competitive RT-PCR using cRNA internal standards:
      identity, quantity, and control.
AB  - Accurate quantification of mRNA by competitive RT-PCR demands that the quality of
      the cRNA internal standard be strictly controlled and that at least two criteria
      should be satisfied. First, genomic DNA should be removed from the total RNA
      being analyzed; second, template DNA should be removed from the cRNA internal
      standard following in vitro transcription. We observed that the routine use of
      RNase-free DNase I is insufficient for removing template DNA from cRNA samples
      and can degrade cRNA. Furthermore, reducing the template DNA before digestion,
      selectively extracting template DNA, and gel fractionation are all ineffective at
      completely eliminating template DNA contamination in cRNA standards. A strategy
      was developed ("inverted" competitive RT-PCR) to quantify template DNA
      contamination in cRNA standards. Regardless of treatment method, a small
      percentage of DNA contamination remained in the products of in vitro
      transcription. Without correction, the number of mRNA copies calculated from
      competitive RT-PCR is systematically overestimated. The number of template DNAs
      contaminating the cRNA samples was remarkably large, though as a percentage of
      the total cRNA, DNA contamination was small and could be easily corrected.

PMID- 12074175
TI  - Influence of fish consumption on the distribution of serum cholesterol in
      lipoprotein fractions: comparative study among fish-consuming and non-fish
      consuming populations.
AB  - The objective of this study was to investigate serum lipoprotein levels in order
      to assess cardiovascular disease (CVD) risk factors between fish-consuming
      populations and non-fish-consuming populations, as it has been speculated that
      fish intake reduces CVD risk. A representative sample of one thousand subjects
      (529 men and 471 women) were selected, with ages ranging from 20 to 70 years,
      from 40 villages belonging to fish-consuming (500) or non-fish-consuming (500)
      populations. Serum lipoprotein lipids such as total cholesterol (TC), high
      density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol
      (LDL-C) were analysed biochemically using standard procedures. The ratios of TC:
      HDL-C and LDL-C: HDL-C were computed. Mean values of serum LDL-C and the ratios
      of LDL-C: HDL-C and TC: HDL-C were significantly lower and HDL-C levels were
      higher in fish-consumers than in non-fish-consumers. The concentrations of HDL-C
      decreased with increasing age, while the reverse was true for LDL-C and for the
      LDL-C: HDL-C and TC: HDL-C ratios. There were significant sex differences for
      certain age groups in both of the population groups. The 5th, 50th and 95th
      percentile cut-off values for these parameters were lower in fish-consumers than
      in non-fish-consumers. The prevalence of individuals at risk of CVD because of
      low HDL-C (<35 mg/dL), high LDL-C (>130 mg/dL) and their atherogenic ratios (LDL
      C: HDL-C >3.5 and TC: HDL-C>4.5) was significantly greater in non-fish-consumers.
      This study highlights that the fish-consuming population had a lower atherogenic
      risk than the non-fish-consuming population. The intake of fish may have
      substantial implications for public health and health economy by decreasing the
      risk of CVD. However, more studies are warranted to better define the mechanisms
      of cardioprotection by dietary fish and fish oils.

PMID- 12074176
TI  - Serum fatty acids, lipoprotein (a) and apolipoprotein profiles of middle-aged men
      and women in South Vietnam.
AB  - In Vietnam, increasing fat consumption is a trend recognized recently in urban
      areas. To obtain a reasonable nutrition status and prevent cardiovascular disease
      (CVD), it is necessary to obtain information on habitual fat intake and
      biochemical parameters as risk factors for CVD in Vietnamese populations.
      Therefore, from the analysis of serum fatty acid composition, fat consumption
      patterns in Vietnamese populations in South Vietnam, with different incomes, are
      discussed in this study. In addition, some risk factors for premature CVD, serum
      lipoprotein (a) and apolipoprotein concentrations are also assessed in these
      Vietnamese populations. The study was carried out in men and women aged 40-59 in
      three different districts: urban (n = 100), suburban (n = 98) and rural (n = 98).
      The results of serum fatty acid composition analysis reflected differences in
      quality fat intake among the three populations. The urban population was
      estimated to consume more vegetable oil but less fish than their rural
      counterparts. Although serum lipoprotein (a) and apolipoprotein B levels were
      below the ranges associated with atherogenesis, ongoing attention to dietary fat
      intake for the prevention of CVD in Vietnamese populations is required.

PMID- 12074177
TI  - Effects of haemoglobin and serum ferritin on cognitive function in school
      children.
AB  - The association between iron deficiency anaemia and cognitive function impairment
      has been widely reported in young children, but whether the impairment is a
      result of iron deficiency per se or a combination of iron deficiency and anaemia,
      and how these conditions interact, is still questionable. Four hundred and twenty
      seven school children from two schools in socioeconomically deprived communities
      were selected in southern Thailand. Iron status was determined by haemoglobin and
      serum ferritin concentrations. Cognitive function in this study was measured by
      IQ test and school performance, including Thai language and mathematics scores,
      using z-scores based on distributions within the same grade and school. Data on
      demography and socioeconomic status were collected by questionnaire answered by
      the parents. Linear regression models were used to investigate the effect of
      anaemia and iron deficiency, reflected by haemoglobin and serum ferritin
      concentration, on cognitive function and school performance. We found that
      cognitive function increased with increased haemoglobin concentration in children
      with iron deficiency, but did not change with haemoglobin concentration in
      children with normal serum ferritin level. Children with iron deficiency anaemia
      had consistently the poorest cognitive function (IQ, 74.6 points; Thai language
      score, 0.3 SD below average; and mathematics score, 0.5 SD below average).
      Children with non-anaemic iron deficiency but with high haemoglobin levels had
      significantly high cognitive function (IQ, 86.5 points; Thai language score, 0.8
      SD above average; and mathematics score, 1.1 SD above average). This study found
      a dose-response relationship between haemoglobin and cognitive function in
      children with iron deficiency, whereas no similar evidence was found in iron
      sufficient children.

PMID- 12074179
TI  - Sources of dietary iron in urban and provincial 4-year-old children in Iran.
AB  - Iron-deficiency anaemia is prevalent in childhood, especially in developing
      countries. Nutritional deficiency is one of the main causes of iron-deficiency
      anaemia, although absorption varies considerably between different dietary items.
      Information on the sources of iron in young children is limited. A study was
      therefore undertaken to investigate the different dietary sources of iron in 151
      healthy children aged 4 years who were selected from two districts of Fars
      province, Iran. Two 3-day dietary diaries with pre- and post-interview were used
      to record the dietary intake of the children. Food and drinks were categorised
      into four groups (animal, plant, drinks and other) to measure the relative
      importance of different sources of iron. Sixty-eight percent of the children
      completed the 3-day dietary diaries in both summer and winter. The results showed
      no statistically significant differences in total daily iron intake between the
      two seasons or between genders. However, the difference in the total daily iron
      intake between children in the city and the provincial district was significant:
      7.73+/-1.75 mg/day and 10.33+/-2.9 mg/day, respectively (P < 0.001). About 75 and
      60% of iron intake came from plant sources in the provincial district and city,
      respectively. The three most important sources of iron for children of the
      provincial district were bread (51%), fruit and vegetables (12%) and meat (7%).
      This pattern was also observed for children living in the city, but with
      different percentages: 27%, 16% and 16%, respectively. In conclusion, total iron
      intakes were similar to those recorded in European countries, but little of the
      intake came from animal sources and substantial differences between city and
      provincial children were recorded.

PMID- 12074178
TI  - Therapeutic effects of NaFeEDTA-fortified soy sauce in anaemic children in China.
AB  - The therapeutic effects of NaFeEDTA-fortified soy sauce on anaemic students were
      investigated. Three hundred and four iron-deficient anaemic school children (11
      17 years) were randomly assigned to three treatment groups: control group
      (consuming non-fortified soy sauce), low-NaFeEDTA group (consuming fortified soy
      sauce, providing 5 mg Fe/day) and high-NaFeEDTA group (consuming fortified soy
      sauce, providing 20 mg Fe/day). Blood haemoglobin (Hb) levels were determined
      before and after 1 month, 2 months and 3 months of intervention. In addition,
      serum iron (SI), serum ferritin (SF), free erythrocytic porphyrin (FEP), total
      iron binding capability (TIBC) and transferritin (TF) were measured before and
      after consumption of soy sauce for 3 months. The results obtained herein show
      that the parameters measured were not changed remarkably within the 3-month
      intervention in the control group (P < 0.05). However, increased Hb, SI, SF and
      TF levels and decreased TIBC and FEP levels were observed in both the high
      NaFeEDTA group (P <0.01) and the low-NaFeEDTA group (P < 0.05). The effectiveness
      of iron intervention in the low-NaFeEDTA group and high-NaFeEDTA group had no
      statistical significance after 3 months. It was concluded that nutritional
      intervention for anaemic students using NaFeEDTA-fortified soy sauce could play a
      positive role in the improvement of iron status and control of anaemia.

PMID- 12074180
TI  - Socioeconomic profile and nutritional status of children in rubber smallholdings.
AB  - This paper will present the socioeconomic profile and nutritional status of
      children aged 1-6 years in the rubber smallholdings of Peninsula Malaysia. A
      total of 323 households were involved in this study. The sociodemographic data
      were obtained through interviews with heads of households using a set of
      questionnaires. Anthropometric measurements were taken from 506 children aged 1-6
      years from these households. The weight and height of the children were compared
      with the reference values of the National Center for Health Statistics (NCHS) and
      the nutritional status was classified based on the recommendations of WHO. The
      average age of the fathers was 39.9+/-8.6 years and 34.4+/-7.0 years for the
      mothers. The mean household size was 6.67+/-2.27. The majority (49.7%) of the
      heads of households received 4-6 years of formal education and 7.9% received no
      formal education. Based on the monthly per capita income, 24.0% were found to be
      in the hardcore poor category, 38.3% fall into the poor category and 37.7% in the
      above poverty income group. The prevalence of stunting and underweight among
      children between the ages of 1-6 years were highest among children from the
      hardcore poor, followed by the poor category and above the poverty line income
      group. Wasting was present in all income groups, with a prevalence of 4.2% found
      among the hardcore poor, 9.4% among the poor group and 8.4% in the above poverty
      income group. The Pearson Product Moment Correlation showed significant
      relationships between household total income and height-for-age (r = 0.131, P =
      0.05) and weight-for-age (r = 0.127, P = 0.05). There were also significant
      correlations between monthly per capita income with height-for-age (r = 0.16, P <
      0.01) and weight-for-age (r = 0.13, P < 0.05). The acreage of land utilised was
      correlated with height-for-age (r = 0.11, P < 0.05), weight-for-age (r = 0.17, P
      < 0.05) and weight-for-height (r = 0.16, P < 0.05). However, stepwise multiple
      regression analysis indicated that the predictor of height-for-age was monthly
      per capita income (R2 = 0.03, P < 0.01) and acreage of land utilised was a
      predictor for weight-for-age (R2 = 0.03, P < 0.01) and weight-for-height (R2 =
      0.01, P < 0.01). Because income and acreage of land utilised have been shown to
      be associated with nutritional status, it is recommended that intervention
      programs that focus on generation of income and diversification of land
      utilisation should be undertaken. A multidiscipline approach involving the
      family, community and government agencies should be applied to any type of
      intervention program.

PMID- 12074181
TI  - Dietary calcium intake in postmenopausal Malaysian women: comparison between the
      food frequency questionnaire and three-day food records.
AB  - The objective of this study was to compare the dietary calcium intakes assessed
      by a quantitative food frequency questionnaire (FFQ) and the three-day food
      record method in 230 Chinese postmenopausal women aged 50-65 years in Kuala
      Lumpur. The results showed that the mean calcium intake from the dietary records
      was 447+/-168 mg/day and 499+/-211 mg/day from the FFQ. The mean difference in
      intake by the two methods was 51.3 mg (95% CI = -30.8-77.9; SD = 181.2, P>0.05),
      which did not differ significantly from zero. Pearson's correlation coefficient
      of 0.56 was obtained between the two methods. Ninety-five percent of the
      individuals classified by food records fell into the same or within-one-quartile
      category when classified by FFQ. Forty-eight percent were classified into the
      same quartile by both methods. No subjects were grossly misclassified by the FFQ.
      The FFQ correctly identified subjects with calcium intakes below the Malaysian
      recommended daily allowance (450 mg/day) with 60% specificity and with 92%
      specificity for women consuming less than 800 mg calcium/day. In conclusion, the
      FFQ developed was a useful, rapid clinical tool for assessing calcium intake and
      identifying postmenopausal Chinese women with low calcium intakes in Malaysia.

PMID- 12074182
TI  - Assessment of a rapid method for assessing adequacy of calcium intake.
AB  - The purpose of this study was to assess the agreement between the 24 h diet
      recall and a short 17-item 24 h food intake recall in assessing calcium intake.
      The calcium intakes of 21 women over the age of 50 were assessed by both methods
      on four occasions. The mean calcium intakes were similar using both methods,
      being 1034+/-398 mg/day by 24 h diet recall and 822+/-412 mg/day (SD) by 17-item
      24 h food intake recall. The 17-item 24 h food intake recall tended to
      underestimate calcium intake compared with the 24 h diet recall, with the limits
      of agreement being between -1197 and -727 below and 370 and 682 mg/day above 24 h
      diet recall values over the four assessments. The 17-item 24 h food intake recall
      identified 8% more women with inadequate calcium intakes than the 24 h diet
      recall method did. Although there is poor agreement in calcium intake between the
      24 h diet recall method and the 17-item 24 h food intake recall, the latter
      provides a quick and simple means for assessing extremes of calcium intake and
      whether day to day calcium intake is adequate.

PMID- 12074183
TI  - Gastrointestinal tolerance of a new infant milk formula in healthy infants:
      multicenter study conducted in Taiwan.
AB  - The objective of this study was to test whether the gastrointestinal tolerance of
      a new infant formula equalled or exceeded the tolerance of other milk-based
      infant formulas, and to compare the tolerance of the new formula to that of human
      milk. This prospective, observational, multicenter, open-label study was
      conducted in Taiwan. Healthy, full-term infants aged 28-98 days were enrolled on
      their current feeding regimen (no treatment assigned). Feeding regimens included
      human milk (HM), a new infant formula (NF, Similac Advance), other marketed
      infant formulas (OF, mainly Enfalac or S-26, HM + NF and HM + OF. Data for stool
      frequency, stool consistency and gastrointestinal intolerance symptoms were
      recorded in study diaries by parents for a period of two weeks. Gastrointestinal
      tolerance was evaluated in 967 infants, of whom 481 (49.7%) received NF, 312
      (32.2%) received OF, 101 (10.4%) received HM + NF, 41 (4.2%) received HM + OF and
      32 (3.3%) received HM. Infants fed HM only had softer and more frequent stools
      than those who received NF only or OF only (P < 0.001). Infants fed NF only had
      softer stools than those fed OF only (P < 0.001), including those fed either
      Enfalac or S-26 (P < 0.001). There were no significant differences between
      feeding groups for the incidence of general intolerance, spit-up or flatulence.
      All feeding regimens were well tolerated. We thereby concluded that NF is well
      tolerated in healthy infants and results in stool consistencies that more closely
      resemble those of infants fed human milk than those of infants fed other
      formulas.

PMID- 12074184
TI  - Effect of Cassia auriculata leaf extract on lipids in rats with alcoholic liver
      injury.
AB  - We studied the effect of administering Cassia auriculata leaf extract to rats
      with experimentally induced liver damage. Hepatotoxicity was induced by
      administering 9.875 g/kg bodyweight ethanol for 30 days by intragastric
      intubation. C. auriculata leaf extract was administered at a dose of 250 mg/kg
      bodyweight daily in one group and 500 mg/kg bodyweight daily in another group of
      alcohol-treated rats. All rats were fed with standard pellets. The control rats
      were also given isocaloric glucose solution. The average bodyweight gain was
      significantly lower in alcohol-treated rats, but improved on supplementation with
      C. auriculata leaf extract. Alcohol supplementation significantly elevated the
      cholesterol, phospholipid and triglyceride concentration in the liver, brain,
      kidney and intestine, as compared with those of the normal control rats.
      Treatment with C. auriculata leaf extract and alcohol significantly lowered the
      tissue lipid levels to almost normal levels. Microscopic examination of alcohol
      treated rat liver showed inflammatory cell infiltrates and fatty changes, which
      were reversed on treatment with C. auriculata leaf extract. Similarly, alcohol
      treated rat brain demonstrated spongiosis, which was markedly reduced on
      treatment with C. auriculata. In conclusion, this study shows that treatment with
      C. auriculata leaf extract has a lipid-lowering effect in rats with
      experimentally induced, alcohol-related liver damage. This is associated with a
      reversal of steatosis in the liver and of spongiosis in the brain. The mechanism
      of C. auriculata leaf extract lipid-lowering potential is unclear.

PMID- 12074185
TI  - Kiwifruit promotes laxation in the elderly.
AB  - Numerous anecdotal reports have suggested that kiwifruit (Actinidia deliciosa)
      has laxative effects. This could be an acceptable dietary supplement, especially
      for elderly people who often present with constipation. We wished to obtain
      objective evidence as to whether or not kiwifruit eaten regularly could promote
      laxation in elderly people. Thirty-eight healthy adults of age > 60 years
      consumed their normal diet, with or without one kiwifruit per 30 kg bodyweight
      for three weeks, followed by a 3-week crossover period. Daily records were taken
      on frequency of defecation and characteristics of the stools. Kiwifruit
      significantly enhanced all tested measures of laxation in these adults. The
      regular use of kiwifruit appeared to lead to a bulkier and softer stool, as well
      as more frequent stool production. Kiwifruit as a natural remedy appears
      palatable to most of the population and provides improved laxation for elderly
      individuals who are otherwise healthy. It is likely that a number of factors in
      the whole fruit are involved, but the nature of the stools suggest fibre is
      important. This study provides evidence of the potential for improvement in bowel
      function, health and well-being through changes in diet.

PMID- 12074186
TI  - Ocular manifestation of vitamin A deficiency among Orang asli (Aborigine)
      children in Malaysia.
AB  - This study determined the prevalence of ocular manifestation of vitamin A
      deficiency in Orang Asli (Aborigine) children. Night blindness was found in 16.0%
      of the children, conjunctiva xerosis in 57.3%, Bitot's spot in 2.8%, corneal
      xerosis in 0.5% and corneal scars in 5.6%. These findings show that history of
      night blindness had sensitivity, specificity and predictive value (positive) of
      47.2, 98.1 and 96.2%, respectively, compared with the standard diagnosis
      procedure using luxometer readings.

PMID- 12074187
TI  - Simultaneous analysis of retinol, beta-carotene and tocopherol levels in serum of
      Vietnamese populations with different incomes.
AB  - In this study, we clarified the status of the fat-soluble vitamins retinol and
      tocopherol, as well as beta-carotene, as antioxidants in the prevention of
      cardiovascular disease in middle-aged Vietnamese populations with different
      incomes. In order to measure simultaneously the serum concentrations of retinol,
      beta-carotene and tocopherol, we carried out high-performance liquid
      chromatography analysis with three separate detectors. The analytical method was
      modified, omitting the saponification process, and used a multi-evaporating
      system with dry ice. This allowed the analysis to proceed more rapidly, use a
      small amount of serum (40 microL) and be free of hexane contamination to the
      environment. The analyses reflected an adequate status of vitamin A (serum
      retinol = 20 microg/dL), but inadequate status of beta-carotene and vitamin E
      (serum beta-carotene <40 microg/dL; serum tocopherol < 600 microg/dL) in all
      three Vietnamese populations. As large numbers of Vietnamese subjects were
      observed with very low serum concentrations of beta-carotene and tocopherol,
      higher consumptions of green and yellow vegetables, fruits, vegetable oils and
      other foods rich in vitamin E are recommended for these Vietnamese populations.

PMID- 12074188
TI  - Socioeconomic status and the prevalence of coronary heart disease risk factors.
AB  - South Asian countries have a high prevalence of coronary heart disease (CHD) in
      line with their economic development. India, in particular, has a high burden of
      CHD. Hence, the aim of the present study was to assess the prevalence of CHD risk
      factors in a semiurban population of Andhra Pradesh, India, in different
      socioeconomic status (SES) groups. Information was collected on socioeconomic
      status, physical activity, cigarette smoking, body mass, blood pressure (BP) and
      serum lipid profiles among a healthy sample of 440 men and 210 women with an age
      range of 20-70 years. Mean levels of serum cholesterol (SC), high density
      lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC) and
      skinfold ratio were found to be higher among women, whereas triglycerides (TG),
      systolic BP and diastolic BP were higher in men. No statistically significant
      differences in body mass index (BMI) or pulse rate were observed between the
      sexes. In men, a significant positive rank correlation (rho = P < 0.05) was
      observed between SES and SC, TG, systolic and diastolic BP, pulse rate and BMI,
      but in women, the same trend was found only with SC, TG, skinfold ratio and age.
      The prevalence (age standardized to the world population of Segi, 95% CI) of
      obesity was 14.37% (11.06-17.68), hypertension 13.13% (9.11-17.15),
      hypercholesterolemia 18.56% (13.88-23.24), hypertriglyceridemia 45.98% (36.47
      55.49) and low HDLC 31.01% (24.25-37.77). In both sexes, the prevalence of
      hypercholesterolemia, hypertriglyceridemia and sedentary life style increased
      among higher SES groups (P < 0.05). Also, an increase in the level of social
      class was positively associated with mean levels of serum cholesterol and
      triglycerides in both men and women. The results demonstrate that higher SES
      groups have greater prevalence of CHD risk factors than lower SES groups.
      Preventive measures are required to reduce the risk factors among higher SES
      groups.

PMID- 12074189
TI  - Nutrition labelling: purpose, scientific issues and challenges.
AB  - Nutrition labels describe the nutrient content of a food and are intended to
      guide the consumer in food selection. The nutrition information provided must be
      selected on the basis of consistency with dietary recommendations. Selection of
      the specific nutrients or food components to be listed should further take into
      account label space, the analytical feasibility of measuring the particular
      nutritional component within the food matrix, and the relative costs of such
      analyses. Nutrition information provided on labels should be truthful and not
      mislead consumers. At the same time, labelling regulations should provide
      incentives to manufacturers to develop products that promote public health and
      assist consumers in following dietary recommendations. It is likely that in many
      countries, there would be some segments of the population that would benefit from
      information about the composition of foods. In these cases, countries should
      consider the need to provide for appropriate labelling and its presentation
      relative to existing guidelines and approaches. As nutrition-labelling efforts
      have evolved, different approaches and legal requirements have been established.
      These create difficulties in developing and harmonizing nutrition information
      listings, which have broad international applications. For these reasons, the
      Codex Guidelines on Nutrition Labeling play an important role to provide guidance
      to member countries when they want to develop or update their national
      regulations and to encourage harmonization of national standards with
      international standards. These Guidelines are based on the principle that no food
      should be described or presented in a manner that is false, misleading or
      deceptive. The Guidelines include provisions for voluntary nutrient declaration,
      calculation and presentation of nutrient information. The Guidelines on Claims
      establish general principles to be followed and leave the definition of specific
      claims to national regulations. Definitions are provided for a number of claims
      (nutrient content, comparative claims, nutrient function claims) as well as
      general requirements concerning consumer information in relation with claims.
      Nutrition labelling by itself cannot solve nutrition problems. It should be seen
      as one of the elements of nutrition policy and should be envisaged in the larger
      perspective of consumer education, which in its turn is part of an overall
      development policy. Exchange of information at the regional and subregional level
      is important, as each country can learn from the experience of others and
      regional co-ordination and co-operation can be developed.

PMID- 12074190
TI  - Nutrition labelling: perspectives of a bi-national agency for Australia and New
      Zealand.
AB  - Australia New Zealand Food Authority (ANZFA) is a bi-national government agency
      forming a partnership between all of Australia's States and Territories and the
      New Zealand government. Australia New Zealand Food Authority employs scientific,
      legal policy, communication and administrative staff in our Australia and New
      Zealand offices. Prior to 1991 each of Australia's States and Territories had
      their own food standards; however, in 1991 Commonwealth legislation was
      introduced to consolidate responsibility for developing food standards in one
      specialist agency and to ensure the uniformity of Standards across all States and
      Territories in Australia. This was extended to New Zealand in 1995 when we became
      a bi-national agency following the signing of a Treaty between Australia and New
      Zealand to develop joint food standards for both countries. Australia New Zealand
      Food Authority's objectives in setting food standards are to: protect public
      health and safety; provide adequate information to enable consumers to make
      informed choices; and prevent misleading or deceptive conduct. Health Ministers
      have recently approved a new Joint Food Standards Code for Australia and New
      Zealand. This is the result of over 6 year's work and many rounds of public
      consultation. The new Code has had extensive input from government agencies,
      industry and consumers. In drafting the new code our emphasis has been on making
      decisions based on sound science and the most up-to-date information available.
      We also recognized the need for Standards to be practical in not imposing
      unnecessary costs on food manufacturers with an inevitable flow on effect to
      consumer prices. The Joint Code will replace both the existing Australian Food
      Standards Code and the New Zealand Food Regulations after a 2-year transition
      period. During the development of the Joint Code a wide range of matters were
      considered in relation to labelling. Amongst these were consumer needs, costs to
      industry, voluntary versus mandatory, enforcement issues, relationship to
      advertising and exemptions. A number of features of the new Code relate
      specifically to labelling and include: warning and advisory statements;
      ingredients lists; date marking; directions for use and storage; nutrition
      information; legibility requirements; and percentage labelling. One of the key
      features of the Joint Code is the requirement for most packaged foods to bear a
      nutrition information panel (NIP). Information must be presented on the amount of
      fat, saturated fat, protein, energy, carbohydrates, sugars and sodium. For the
      majority of foods the label is the first and only source of information regarding
      the nutritional content of food purchased. Mandatory nutrition labelling will
      ensure that consumers are provided with key nutritional information about foods.
      Single ingredient produce such as fruit and vegetables, and some other foods such
      as spices, tea and coffee will be exempt. The new requirements will give
      consumers more nutritional information to allow product comparison. All products
      will be required to provide information on these nutrients on both a per 100 g
      basis and in terms of an average serving. In addition to the mandatory nutrient
      declarations NIP are also required to carry additional data for any substance for
      which a nutrition claim is made. During the 2-year transition period to December
      2002 ANZFA will be working with industry, enforcement agencies and consumers to
      help to ensure that there is a smooth transition to the Joint Food Standards
      Code.

PMID- 12074191
TI  - Nutrition labelling: European Union and United Kingdom perspectives.
AB  - The growing public interest in the relationship between diet and health and
      increasing public health problems in Europe were among the determining factors
      which led the European Commission to propose harmonized legislation on nutrition
      labelling. The Directive which was adopted in 1990 primarily aimed at providing
      information which helps consumers to make an informed choice and assist action in
      the area of nutrition education for the public. The provisions of the Directive
      are voluntary but become obligatory if the manufacturer decides to make a
      'nutritional claim'. Where nutrition labelling is applicable, the information may
      be given in two formats: group 1, energy value and the amounts of protein,
      carbohydrate and fat ('Big 4'); or group 2, energy value and the amounts of
      protein, carbohydrate, sugars, fat, saturates, fibre and sodium 'Big 8'). A claim
      for one of the following sugar, saturated fat, fibre or sodium automatically
      triggers group 2 information. Additional information can be provided on the
      amounts of starch, polyols, mono-unsaturates, poly unsaturates, cholesterol and
      any of the vitamins or minerals. The nutrition information must be given per 100
      g or 100 mL of food but may also be declared per quantified serving of food, or
      per portion where the number of portions is indicated on the label. The
      information must be presented together in one place in tabular form. A revision
      of the Nutrition Labelling Directive is due and will address issues such as the
      voluntary character of the legislation, the amount of information given and its
      presentation, legibility and consumer understanding.

PMID- 12074193
TI  - Biomarkers, yesterday, today and tomorrow: the basis for health claims.
AB  - The development of useful and accurate biomarkers for predicting outcomes of food
      based interventions is becoming more and more important, given the emphasis being
      placed on ingredients in foods contributing to disease risk reduction and optimal
      health promotion. With the human genome now laid bare, opportunities abound to
      barcode individuals with their risk profiles. The massive increase in DNA
      sequence information together with the development of new technologies such as
      genomics, proteomics and bioinformatics, has resulted in a much greater capacity
      to determine individual risk profiles. Screening for biomarkers at the gene or
      protein expression level using microarray technology has the potential to
      identify new biomarkers for disease diagnosis. Whether these techniques will
      enable a better understanding of food-gene interactions to permit health claims
      rather than better therapeutic treatment (at high economic cost) remains to be
      demonstrated.

PMID- 12074192
TI  - Current status of nutrition labelling and claims in the South-East Asian region:
      are we in harmony?
AB  - This review includes the situation of nutrition labelling and claims in six
      countries in South-East Asia: Brunei, Indonesia, Malaysia, Philippines, Singapore
      and Thailand. With the exception of Malaysia, there is no mandatory nutrition
      labelling requirements for foods in these countries except for special categories
      of foods and when nutritional claims are made for fortified or enriched foods.
      Nevertheless, several food manufacturers, especially multinationals, do
      voluntarily label the nutritional content of a number of food products. There is,
      therefore, increasing interest among authorities in countries in the region to
      start formulating regulations for nutrition labelling for a wider variety of
      foods. Malaysia has proposed new regulations to make it mandatory to label a
      number of foodstuffs with the four core nutrients, protein, carbohydrate, fat and
      energy. Other countries have preferred to start with voluntary labelling by the
      manufacturers, but have spelt out the requirements for this voluntary labelling.
      The format and requirements for nutrition labelling differ widely for countries
      in the region. Some countries, such as Malaysia, closely follow the Codex
      guidelines on nutrition labelling in terms of format, components to be included
      and mode of expression. Other countries, such as the Philippines and Thailand,
      have drafted nutrition labelling regulations very similar to those of the
      Nutrition Labeling and Education Act (NLEA) of the United States. Nutrition and
      health claims are also not specifically permitted under food regulations that
      were enacted before 1998. However, various food products on the market have been
      carrying a variety of nutrition and health claims. There is concern that without
      proper regulations, the food industry may not be certain as to what claims can be
      made. Excessive and misleading claims made by irresponsible manufacturers would
      only serve to confuse and mislead the consumer. In recent years, there has been
      efforts in countries in the region to enact regulations on nutrition claims.
      Recently enacted regulations or amendments to existing regulations of almost all
      the countries reviewed have included provisions for nutrition claims. Malaysia is
      in the process of gazetting regulations to clearly stipulate the permitted
      nutrition claims and the conditions required to make these claims along the
      guidelines of Codex Alimentarius Commission. Only two countries in the region
      permit health claims to be made - Indonesia and Philippines. Other countries in
      the region are following developments in Codex and examining the need for
      allowing these claims. There are more differences than similarities in the
      regulations on nutrition labelling and claims among countries in the South-East
      Asian region as no previous efforts have been made to address these. Hopefully,
      through this first regional meeting, countries can initiate closer interaction,
      with a view to working towards greater harmonization of nutrition labelling and
      health claims in the region.

PMID- 12074194
TI  - International guidelines and experiences on health claims in Europe.
AB  - The relationship between nutrition and health is gaining public acceptance and
      consumers are increasingly health-conscious and want to obtain more information
      about the food they buy. There is a legal void with regard to health claims in
      the European Union. The framework labelling legislation prohibits 'attributing to
      any foodstuff the property of preventing, treating or curing a human disease or
      referring to such properties'. In the absence of a specific Directive on claims
      for foodstuffs, EU member states apply different interpretations of the existing
      labelling legislation. Therefore, it may occur that a claim which is permitted in
      one country may be prohibited in another one, and vice versa. Because of this,
      manufacturers have to deal with a variety of regulations, guidelines and codes of
      conduct. As regards national self-regulation systems (guidelines, consensus
      documents, voluntary codes of practice, joint interpretation of law),
      increasingly their development in EU countries (UK, France, Belgium, Netherlands,
      Spain, Sweden, Finland), is an attempt to remedy the situation of legal
      uncertainty. In most countries, a coalition of industry experts, enforcement
      authorities, consumer representatives, and scientists was involved in the
      elaboration of rules for the scientific justification and formulation,
      communication and presentation of health claims. At the international level,
      Codex Alimentarius is currently debating a draft on Enhanced Function Claims and
      Reduction of Disease Risk Claims. The draft recommendation is currently at step 3
      of the Codex procedure. A lot of work has been undertaken internationally
      (Codex), in the EU (FUFOSE) and beyond (Council of Europe) in order to
      demonstrate that scientific substantiation of claims is possible and to establish
      valid criteria for this process.

PMID- 12074195
TI  - Newly established regulation in Japan: foods with health claims.
AB  - The Japanese government enacted a new regulatory system called 'Foods with health
      claims' in April 2001, which consists of 'Foods for Specified Health Use' (FOSHU)
      and 'Foods with Nutrient Function Claims' (FNFC). The FOSHU was set up by the
      Ministry of Health and Welfare in 1991 to approve descriptions on a label
      regarding an effect of food on the human body. It was enacted as a part of 'food
      for specified dietary use' under the Nutrition Improvement Law. There are three
      important requirements for FOSHU approval. The first is scientific evidence of
      the efficacy, including clinical testing. The second is safety for consumption.
      The third is analytical determination of the effective component. At present
      there are 293 items approved as FOSHU. Most of the descriptions of foods under
      the FOSHU system are similar to the category of enhanced function claims of
      Codex. Under FNFC, 12 vitamins (vitamin A, B1, B2, B6, B12, C, E, D, biotin,
      pantothenic acid, folic acid, and niacin) and two minerals (calcium and iron) are
      standardized. These claims are similar to the nutrient function claims approved
      by Codex in 1997. It is desirable that the Japanese administration and the food
      industry cooperate with ASEAN countries to work together in the development and
      promotion of nutrition and health claims on foods.

PMID- 12074196
TI  - Transposable elements and the evolution of eukaryotic complexity.
AB  - Eukaryotic transposable elements are ubiquitous and widespread mobile genetic
      entities. These elements often make up a substantial fraction of the host genomes
      in which they reside. For example, approximately 1/2 of the human genome was
      recently shown to consist of transposable element sequences. There is a growing
      body of evidence that demonstrates that transposable elements have been major
      players in genome evolution. A sample of this evidence is reviewed here with an
      emphasis on the role that transposable elements may have played in driving the
      evolution of eukaryotic complexity. A number of specific scenarios are presented
      that implicate transposable elements in the evolution of the complex molecular
      and cellular machinery that are characteristic of the eukaryotic domain of life.

PMID- 12074198
TI  - Quantifying gene expression.
AB  - Identifying those genes that are expressed and at what levels is an essential
      part of almost any biological inquiry at the cellular level. Techniques such as
      Northern blot have been in existence for decades to perform this task, but
      advances in molecular biology and bioinstrumentation have led to the development
      of a variety of new techniques with a range of sensitivities, throughputs and
      quantitative capabilities. This review focuses on the latter issue. For several
      commonly used gene expression techniques, the extent and range of quantitative
      applicability are reviewed, and approaches for maximizing the accuracy and
      precision of these measurements are discussed.

PMID- 12074199
TI  - Touching a chord--on being a doctor.

PMID- 12074197
TI  - Arabidopsis transcription factors and the regulation of flowering time: a genomic
      perspective.
AB  - The availability of the Arabidopsis genome sequence allows for novel approaches
      in the analysis of many aspects of plant biology. Approximately 6% of Arabidopsis
      genes code for transcription factors, which can be grouped into different
      families according to similarities within the DNA binding domains. Transcription
      factors are critical regulatory components of the pathways that underpin many
      aspects of plant growth, development, and physiology. In particular, a
      substantial number of them are emerging as having crucial roles in controlling
      one of the most important, but complex, steps in the plant life cycle: the
      transition to flowering. Genome-wide studies offer the opportunity to gain a
      comprehensive understanding of this polygenic process, making it possible to
      appreciate both the large number of genes involved, as well as the complex
      regulatory networks into which those genes are integrated.

PMID- 12074200
TI  - Phosphodiesterase inhibition: erectile dysfunction is only part of the story.

PMID- 12074201
TI  - Surveillance study of bacteraemic episodes in febrile neutropenic children.
AB  - We prospectively studied the type, frequency and outcome of infections in 513
      patients with 762 consecutive episodes of febrile neutropenia (FN) over a five
      year period between 1995 and 1999 in a single paediatric oncology unit. The
      findings were then compared with a similar study carried out in our unit between
      1990 and 1994. The types of bacterial isolates and sensitivity patterns were also
      studied to identify trends and to gauge the suitability of antibiotics chosen for
      empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although
      70% of patients did not have an obvious site of sepsis. The majority of isolates
      (61.9%) were gram-negative bacteria, a consistent finding throughout the study
      period. Resistance to ceftazidime, amikacin and imipenem among gram-negative
      bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among
      gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were
      encountered. There were 36 sepsis-related deaths. Factors associated with a fatal
      outome were prolonged capillary refill time, hypotension, fever above 39 degrees
      C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis.
      A change to our current choice of empirical antibiotics for FN, comprising
      ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively
      high resistance rates found.

PMID- 12074202
TI  - Cervical metastasis in papillary carcinoma of the thyroid: a histopathological
      study.
AB  - The tendency of well differentiated thyroid carcinoma to remain localised, and
      the slow progression of these tumours, have supported the belief that this
      disease behaves as a low grade malignancy. However, with differentiated
      carcinomas of the thyroid the incidence of nodal metastasis is highest in the
      papillary subgroup, and the importance of cervical metastases is being
      increasingly recognised. We have performed and prospectively analysed 17 neck
      dissections in 13 patients with clinically N+ve necks and papillary carcinoma of
      the thyroid. In all 17 neck dissections, metastatic deposits of papillary
      carcinoma of the thyroid were seen, with metastases found in all levels. Our
      findings of positive lymph nodes in all levels of the neck, with no predictable
      pattern of spread, and skip metastases, support an aggressive surgical approach
      to the treatment of cervical metastatic papillary carcinoma of the thyroid.

PMID- 12074204
TI  - The importance of coded radiographic labelling in clinical practice.
AB  - Locating a particular radiograph from a radiographic envelope can be a
      frustrating and time-consuming process. The aim of this study was to evaluate the
      role of colour and number coding of radiographs in reducing time taken to locate
      films and thereby improve efficiency. The time taken by clinicians to retrieve
      films from a radiographic envelope was measured. The radiographs were coded by
      number, number and colour or not at all. Results show a statistically significant
      reduction in time taken to find number coded versus non-coded radiographs. A
      further benefit was gained by using colour coding in conjunction with number
      coding. We recommend the use of colour and number coding of radiographs in
      clinical practice.

PMID- 12074203
TI  - Effectiveness of quinine in treating muscle cramps: a double-blind, placebo
      controlled, parallel-group, multicentre trial.
AB  - To determine the efficacy and safety of quinine in treating nocturnal muscle
      cramps we performed a double-blind, placebo-controlled, parallel-group,
      multicentre trial in 17 general practice centres in Germany. Ninety-eight
      patients aged 18-70 years with more than six muscle cramps in two weeks were
      enrolled. A two-week run-in period without treatment was followed by two weeks of
      treatment with 400 mg quinine or placebo per day and a wash-out period of two
      weeks without treatment. The primary outcome measure was the reduction in the
      number of muscle cramps between the run-in and treatment periods. The intensity
      of cramps, number of nights with cramps, sleep disturbance and intensity of pain
      were recorded as secondary outcome measures. At baseline the median number of
      cramps was 12 in two weeks in both groups. The median reduction between the run
      in and therapy phases was eight (95% CI 7-10) versus six (95% CI 3-7) muscle
      cramps during quinine and placebo treatment; 36 (80%) participants in the quinine
      group and 26 (53%) in the placebo group had a reduction of at least 50% in the
      number of muscle cramps. Frequency, intensity and pain at night showed a
      statistically significant difference in favour of quinine. The improvement was
      more evident according to physician assessment than patient assessment; this is
      corroborated by the high placebo response rate. No significant differences were
      found between the two groups with respect to side-effects. Short term treatment
      with 400 mg quinine per day can effectively prevent nocturnal leg cramps in
      adults without relevant side-effects.

PMID- 12074205
TI  - Monitoring dietary compliance in coeliac disease using red cell distribution
      width.
AB  - Red cell distribution width (RDW) as measured on modern blood analysers is a
      sensitive marker of nutritional deficiency affecting red blood cell production
      and maturation. Such deficiencies are common in coeliac disease and it may
      therefore be possible indirectly to assess response to a gluten-free diet by
      monitoring the RDW. We measured RDW, iron, B12, folate and endomysial antibodies
      (EMA) in 46 newly diagnosed coeliac patients at diagnosis and after a gluten-free
      diet. RDW was elevated in 76% of patients at diagnosis. There was a significant
      decrease in RDW (17.3% vs 13.8%) after 12 months of diet, corresponding to sero
      conversion of EMA and normalisation of serum iron, B12 and folate levels. We
      conclude that monitoring RDW is a simple indirect means of assessing response to
      a gluten-free diet in coeliac disease.

PMID- 12074206
TI  - Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo
      controlled study in patients receiving stable insulin therapy.
AB  - The glycaemic and lipid effects of treatment with pioglitazone in combination
      with a stable insulin regimen were evaluated in patients with type 2 diabetes.
      Patients (n=566) receiving stable insulin regimens for > or = 30 days yet who had
      HbA1c > or = 8.0% and C-peptide > 0.7 microg/l were randomised to receive once
      daily 15 mg pioglitazone, 30 mg pioglitazone, or placebo in a 16-week
      multicentre, double-blind, placebo-controlled trial. Per study protocol, the
      insulin dose was to remain unchanged, but could be decreased in response to
      hypoglycaemia. At the end of double-blind treatment, patients receiving
      pioglitazone (15 mg or 30 mg) showed statistically significant mean decreases
      relative to baseline HbA1c (-1.0 and -1.3, respectively; p<0.0001) and fasting
      plasma glucose (FPG) (-34.5 mg/dl [-1.92 mmol/l] and -48.0 mg/dl [-2.67 mmol/l],
      respectively; p<0.0001); these differences compared with placebo were also
      significant (p<0.0001). Pioglitazone (15 or 30 mg) yielded significant increases
      in HDL-C levels (mean increases ranging from +7.1% to + 9.3%) compared with
      baseline or placebo (p<0.01). The 30 mg dose also significantly reduced mean
      triglyceride levels (-23.7%) compared with placebo (p=0.0218). No consistent
      changes in TC or LDL-C levels were observed. The incidence of adverse events was
      similar in all treatment groups, although the incidences of weight increase,
      hypoglycaemia and oedema were higher among patients receiving insulin plus
      pioglitazone. There was no evidence of hepatotoxicity or drug-induced elevations
      of serum ALT > or = 3 x ULN. Pioglitazone, when added to stable insulin regimens,
      significantly improved HbA1c and FPG in type 2 diabetes. Pioglitazone treatment
      also provided significant benefit with respect to plasma HDL-C and triglyceride
      levels. Whether these lipid changes have an impact on overall diabetic
      complications remains to be determined.

PMID- 12074207
TI  - Antimicrobial drug use in dermatology in a teaching hospital in western Nepal.
AB  - Medical audit is supposed to oversee, monitor and analyse standards of medical
      treatment at all levels of the healthcare delivery system. This study was
      undertaken to monitor the prescribing of antimicrobial drugs for patients seeking
      treatment in the dermatology outpatient department of the Manipal Teaching
      Hospital in Nepal. A total of 292 dermatology prescriptions of patients attending
      the dermatology OPD were collected between July 2000 and June 2001. Prescriptions
      for antimicrobial agents were separated from the total prescriptions collected,
      and evaluated. There were more female patients (58.2%) than male (41.8%) in our
      study; most were in the 21-40 year age group. The commonest cutaneous infections
      were acne (15.8%) followed by fungal infections (14.8%). Of the 292 prescriptions
      audited, 149 contained antimicrobial agents, constituting 36% of the total number
      of drugs prescribed. Of 256 antimicrobials prescribed, 63% were topical and 37%
      systemic; 5% were generic, 29% were from the essential drug list of Nepal, and
      15% were fixed-dose combinations. Most of the patients received one or two
      antimicrobials, 50% of which were antibacterials and 40% antifungals. Though the
      selection of antimicrobial drugs used in dermatology was largely rational,
      anomalies were observed, and these issues were discussed with clinicians in
      relation to various aspects of drug use. The results indicate there is scope for
      improving prescribing habits. A periodic audit of drug prescribing is desirable
      in rationalising prescribing practice.

PMID- 12074208
TI  - 13. New biological therapies for breast cancer.
AB  - The exploitation of biological differences between normal and malignant cells is
      a logical approach to novel treatments for breast cancer. The potential targets
      for such therapy include the products of proto-oncogenes and oncogenes,
      inhibition of growth factor receptor signalling and the immunological
      exploitation of antigenic differences between normal and malignant cells.
      Monoclonal antibody technology was heralded as a potential 'magic bullet' for
      cancer therapy following its discovery in the mid-1970s, but it is only in the
      past few years that such technology has entered mainstream clinical practice. The
      humanised murine monoclonal antibody to HER2 (trastuzumab) has significant anti
      tumour activity but with minimal toxicity, and has been licensed for use in
      patients with advanced breast cancer. A different approach has been the use of
      enzyme inhibitors to interfere with the signalling pathways downstream of growth
      factor receptors (e.g. farnesyl transferase inhibitors). It is likely that
      effective targets for such therapies will be identified in the next few years.
      There have been significant advances in our understanding of human immunology
      which have coincided with the identification of so-called tumour-associated
      antigens (TAA). These developments have resulted in a resurgence of interest in
      tumour immunotherapy. Peptides derived from these TAAs have been used to generate
      tumour-specific immune responses. An alternative strategy has been to immunise
      patients using viral vectors and plasmid cDNA encoding the TAA. In some studies,
      notably those in patients with advanced melanoma, significant clinical responses
      have been observed. Cell-based strategies including autologous tumour cell
      vaccines, allogeneic tumour cell vaccines and dendritic cell vaccines have been
      used, and significant responses have been reported in several studies. Few of
      these methods have so far been applied to breast cancer, but the possible
      benefits and drawbacks of such an approach will be discussed.

PMID- 12074209
TI  - 14. Breast cancer prevention.
AB  - Increased risk of breast cancer may result from potentially modifiable causes
      such as endogenous hormone levels, obesity, HRT, and non-lactation, or non
      modifiable factors including genetic susceptibility and increasing age. The Gail
      model, based on known factors, may be useful for estimating lifetime risk in some
      individuals, but those risk factors that are easier to modify may have a limited
      impact on the totality of breast cancer. Tamoxifen prevention still remains
      contentious, with a significant reduction in risk of breast cancer in women given
      tamoxifen in the NSABP P1 study but no effect in the Italian and Royal Marsden
      trials. Raloxifene, tested in the MORE trial, reduced the incidence of breast
      cancer by 65% but this was restricted to oestrogen receptor positive tumours.
      Lifestyle factors such as diet, obesity, exercise and age at first full term
      pregnancy and number of pregnancies have a mild to moderate impact on risk, so
      may have little effect on the incidence of breast cancer. Reduction of alcohol
      intake could lead to a modest reduction in the risk of breast cancer but possibly
      adversely affect other diseases. Fat reduction and GnRH analogue reduce
      mammographic density but have not yet been shown to affect risk. For women with
      BRCA1/2 mutation, options include unproven surveillance and prophylactic
      mastectomy with an unquantified risk reduction. Interesting new candidates for
      chemoprevention include aromatase inhibitors, new generation SERMs, demethylating
      agents, non-selective COX inhibitors, tyrosine kinase inhibitors and polyamine
      synthetic inhibitors.

PMID- 12074210
TI  - Management of acute and cutaneous porphyrias.
AB  - The porphyrias comprise a group of disorders of the haem biosynthesis pathway
      that can present with acute neurovisceral symptoms, skin lesions or both. Acute
      porphyrias present with severe abdominal pain, confusion and seizures which may
      be life-threatening. Specific treatment with haem preparations should be
      instituted as soon as possible following confirmation of increased excretion of
      porphobilinogen in the urine. Supportive treatment includes opiate analgesia,
      monitoring for and treating complications such as hypertension and hyponatraemia.
      Follow-up should include counselling on lifestyle modification involving
      avoidance of alcohol, smoking and known porphyrogenic drugs and diet.
      Identification and counselling of at risk relatives is essential. The cutaneous
      porphyrias result from porphyrin-induced photosensitivity and can present with
      either acute photosensitivity or skin fragility and blisters. All cutaneous
      porphyrias can be alleviated by avoidance of sunlight. Treatment of
      erythropoietic protoporphyria involves administering large doses of beta
      carotene, which may improve tolerance to sunlight. Porphyria cutanea tarda can be
      effectively treated by phlebotomy or low dose chloroquine. Congenital
      erythropoietic porphyria is a rare, early onset, severe, photomutilating
      condition for which bone marrow transplantation has been shown to be successful.

PMID- 12074212
TI  - Immunisation with a pneumococcal 7-valent conjugate vaccine.
AB  - Pneumococcal disease causes approximately 1 million deaths a year worldwide in
      children aged younger than 5 years. Increasing antibiotic-resistant strains have
      made management of pneumococcal disease difficult. A pneumococcal 7-valent
      conjugate vaccine (PNCRM7) has been shown to prevent invasive disease in young
      children; it has also demonstrated a modest impact on the prevention of otitis
      media. This conjugated vaccine provides a consistent immune response in infants
      and young children and can be administered simultaneously with other childhood
      vaccines. It is generally well tolerated, with local reactions similar to those
      observed with other licensed childhood vaccines. The objective of this review is
      to discuss the clinical efficacy, immunogenicity and safety of PNCRM7.

PMID- 12074211
TI  - Clinical management of childhood osteoporosis.
AB  - A current working definition of osteoporosis in children is 'fragility fractures
      in association with low bone mass'. This review illustrates the determinants of
      bone mass and fracture risk. We elucidate the pathophysiology and causes of
      osteoporosis in various childhood disorders, with a particular focus on the
      commonest iatrogenic problem, glucocorticoid-induced osteoporosis. We discuss
      clinical evaluation, investigation and multidisciplinary management including
      lifestyle advice, diet, physiotherapy and occupational therapy, drug treatments
      and monitoring for children with osteoporosis. We also emphasise the important
      concepts of bone mass assessment and interpretation in children.

PMID- 12074213
TI  - Current concepts in venous thromboembolism and major lower limb orthopaedic
      surgery.
AB  - Venous thromboembolism remains a major cause of morbidity and mortality among
      patients undergoing major orthopaedic surgery. With improved surgical techniques,
      the use of heparin-based thromboprophylactic agents has allowed significant
      advances in the prevention of thrombosis during the past 30 years. With an aging
      population and the growing burden of degenerative joint disease, the management
      of this preventable disease remains at the forefront of surgical care. Despite
      the use of the supposedly most effective antithrombotic agents (low-molecular
      weight heparins), recent studies have highlighted considerable prevalence of
      thrombosis, especially among hip fracture patients. New prevention strategies
      include a greater use of existing therapies, combining chemical and mechanical
      methods, extending the duration of prophylaxis and, most importantly, developing
      more effective agents with improved benefit to risk ratios.

PMID- 12074214
TI  - Incorrectly aligned fly leads inside the ECG machine causing 'ischaemic' changes.
AB  - We describe a case in which a young woman was inappropriately diagnosed as having
      ischaemic heart disease after presenting with exertional neck pain and an
      abnormal ECG. Diffuse Q-wave and T-wave inversion changes were later attributed
      to erroneous placement of fly leads inside the ECG machine at a recent service.
      Clinicians should be aware of this uncommon cause of incorrect lead connections,
      which can result in unnecessary investigations and treatment.

PMID- 12074216
TI  - Fulvestrant: a review of its development, pre-clinical and clinical data.
AB  - Hormone therapy is the most important systemic treatment of hormone receptor
      positive breast cancer at all stages. Selective oestrogen receptor modulators
      (SERMs), such as tamoxifen, the mainstay of hormone receptor positive breast
      cancer manipulation for many years, are limited by their agonist actions.
      Oestrogen-like activity of these drugs may stimulate cancer growth such as in the
      endometrium and is a mechanism of resistance in breast cancer. Fulvestrant, the
      first of a new class of drugs, an oestrogen receptor down regulator, may have
      advantages over tamoxifen in the treatment of oestrogen-dependent disease. The
      pre-clinical development and early clinical data of fulvestrant are reviewed.
      Fulvestrant was as effective as the aromatase inhibitor anastrazole in second
      line advanced breast cancer. The phase III trial of fulvestrant versus tamoxifen,
      as first-line treatment for metastatic breast cancer, has completed accrual and
      is maturing. Fulvestrant has useful activity against breast cancer as well as a
      favourable side-effect profile and is likely to represent a useful addition to
      the fight against hormone dependent breast cancer. Its place will be better
      defined by ongoing clinical trials.

PMID- 12074215
TI  - Tadalafil (Cialis) for men with erectile dysfunction.
AB  - Tadalafil is an inhibitor of phosphodiesterase type 5, and is currently
      undergoing regulatory review in the US and in Europe. Its chemical structure is
      significantly different from sildenafil, and in vitro studies confirm significant
      potency for PDE5 inhibition, with little activity against most of the other
      isoforms of the enzyme including PDE6, which is the isoform of the enzyme found
      within the retina. The half-life of tadalafil is 17.5 hours and clinical studies
      suggest significant activity 24 hours post-dosing. As with sildenafil, efficacy
      depends upon a normal sexual stimulus, and the drug can taken be as required.
      Tadalafil is effective in the treatment of men with erectile dysfunction, and it
      appears to have a relatively mild side-effect profile, with no visual side
      effects noted.

PMID- 12074217
TI  - Increased serum ferritin levels in active Behcet's disease.
AB  - There is no routine test to evaluate the activity of Behcet's disease (BD).
      Ferritin as a serum predictor of iron storage is an important acute phase
      reactant. In this study, we assessed serum ferritin levels in patients with
      active BD and compared them with those of patients with inactive BD. We aimed to
      show the relationship between ferritin and BD. The patients with BD were
      subdivided into two groups according to disease activity: active (24 patients; 18
      men and 6 women, average age 36.5 +/- 4.9 [28-45] years), and inactive (20
      patients; 16 men and 4 women, average age 37.2 +/- 5.2 [30-49] years). Twenty
      healthy volunteers (15 men and 5 women; average age 38.2 +/- 4.6 [30-47] years)
      served as controls. Patients with active BD had significantly higher serum
      ferritin levels (p=0.0001) than the inactive and control groups. Ferritin levels
      in patients with inactive BD did not differ significantly from healthy control
      subjects (p=0.687). We concluded that in patients with active BD, serum ferritin
      levels are increased and do not reflect serum iron levels.

PMID- 12074218
TI  - Myelofibrosis: response to busulfan after hydroxyurea failure.
AB  - We report a case of myelofibrosis with myeloid metaplasia (MMM) that responded
      dramatically to oral busulfan treatment after failure of hydroxyurea. Although
      busulfan treatment of this disease has fallen out of favour due to the favourable
      toxicity profile of hydroxyurea and reports of efficacy of interferon-alpha, our
      observation suggests there may still be a role for busulfan treatment of MMM in
      the setting of hydroxyurea or interferon failure or intolerance.

PMID- 12074219
TI  - Submandibular Castleman's disease.
AB  - Castleman's disease is a rare benign lymphoid tumour of unknown aetiology, which
      usually appears as a solitary mediastinal mass. We report an unusual case of
      Castleman's disease, an asymptomatic submandibular mass in the lower jaw, and we
      discuss the computed tomography appearance.

PMID- 12074220
TI  - Chronic renal failure in a patient with Sotos syndrome due to autosomal dominant
      polycystic kidney disease.
AB  - Sotos syndrome is characterised by accelerated growth, acromegalic appearance,
      mental retardation and social maladjustment. Most cases are sporadic, but
      familial cases have also been reported. We report a case of Sotos syndrome
      presenting with chronic renal failure due to autosomal dominant polycystic kidney
      disease (ADPKD). Ultrasonographic examination of the patient, his father and
      other family members revealed polycystic kidneys. Renal failure was present only
      in the Sotos case, who also had considerably larger cysts than other family
      members. We suggest that the underlying mechanism responsible from the somatic
      overgrowth in Sotos syndrome may also be linked with the development of larger
      cysts and earlier onset of renal failure in ADPKD. Although Sotos syndrome has
      been associated with urological abnormalities, chronic renal failure is very
      rare. To our knowledge, Sotos syndrome associated with ADPKD has not been
      reported before.

PMID- 12074221
TI  - Giant myelolipoma of the right adrenal gland.
AB  - Adrenal myelolipoma is an unusual, benign and hormonally inactive tumour composed
      of mature adipose and haematopoietic tissue. In the past, these tumours were
      accidentally discovered at autopsy. Today, they are found much more frequently
      and incidentally, mainly because of the widespread use of ultrasonography,
      computed tomography and magnetic reasonance imaging. Adrenal myelolipoma is
      usually unilateral and asymptomatic. The case of a 52-year-old female patient,
      surgically treated for a symptomatic giant myelolipoma of the right adrenal
      gland, is reported, together with a review of the literature.

PMID- 12074222
TI  - Enamel fluoride retention after application of fluoride-containing rubber cups.
AB  - PURPOSE: To compare the fluoride retention in bovine enamel after using fluoride
      containing rubber cups or a conventional rubber cup in combination with a
      fluoride-containing polishing paste. MATERIALS AND METHODS: From each of 20
      bovine incisors, 5 enamel slabs with a diameter of 3 mm were sectioned and
      assigned to 5 groups (A,B,C,D,E). Group A was left untreated and served as the
      negative control. Group B was polished with a rubber cup combined with a fluoride
      containing prophylaxis paste for 10 s (Hawe Cleanic). Groups C and D were treated
      in the same manner by using a fluoride-containing rubber cup with 2,262 ppm or
      9,048 ppm fluoride as NaF. Group E enamel was brushed for 10 s with a toothbrush
      and a slurry of distilled water and fluoride gel with 12,500 ppm fluoride as NaF
      and AmF (Elmex Gelee) and served as the positive control. Th e specimens were
      analyzed using the method of Caslavska et al. After determining the KOH soluble
      fluoride on the enamel surface, the content of structurally bound fluoride was
      analyzed in three consecutive layers of 30 microm. ANOVA with Bonferroni
      correction was used for statistical analysis (P< 0.05). RESULTS: For the KOH
      soluble fluoride, Groups B and D accumulated more KOH-soluble fluoride than the
      negative control and less than the positive control. With respect to the
      structurally bound fluoride, the accumulation in Group D was higher when compared
      to all other groups. It was concluded that a rubber cup with 9,048 ppm fluoride
      may be an effective alternative to the use of a fluoride-containing prophylaxis
      paste.

PMID- 12074224
TI  - Primary preparation of class II cavities with oscillating systems.
AB  - PURPOSE: To assess the effectiveness and side effects of three sonoabrasive
      systems and conventional rotary cavity preparation. MATERIALS AND METHODS:
      Standardized artificial carious lesions were placed in 48 human premolars at
      mesial and distal surfaces. Three dentists prepared eight cavities each using (1)
      diamond burs, (2) Sonicflex 2000 L/N (HS), (3) an experimental air scaler
      (HS.EXP), and (4) the Piezon Cavity System (PCS). A small hemispherical
      preparation tip (Sonicsys micro) was utilized with the airscalers in Groups 2 and
      3. Loss of substance was determined by weighing. Residual caries and damage to
      the adjacent tooth were assessed by two calibrated investigators. Each cavity was
      digitally photographed prior to planimetrical measuring of its circumferential
      dimension. Quality of the cavities' margins was examined by SEM. RESULTS: Rotary
      preparation required less time (4 minutes 53 seconds) than oscillating
      preparation with HS (6 minutes 45 seconds) or PCS (7 minutes 45 seconds),
      (Scheffe, P< 0.05). Preparation with HS.EXP (5 minutes 52 seconds) was not
      different from rotary and HS. 64% of all cavities were completely excavated, 28%
      showed distinct and 8% marked residual caries. However, chi2-tests did not reveal
      differences in caries removal between the systems. Oscillating preparation with
      HS as well as the experimental air scaler in combination with the hemisphere
      resulted in less trauma to adjacent tooth surfaces than rotary preparation and
      the PCS system, (chi2-tests P< 0.05). HS.EXP caused less loss of substance
      (Scheffe, P< 0.05). Regarding circumferential extension of the cavities, there
      were no differences between the groups.

PMID- 12074223
TI  - Influence of anesthetic flow rate delivered by the Wand Local Anesthetic System
      on pain response to palatal injections.
AB  - PURPOSE: To compare pain response between two different flow rates (slow versus
      fast) of local anesthetic solution injected into palatal tissue using the
      recently available Wand Local Anesthetic System (WLAS), which provides the
      technologic advance to permit reliable replication of constant injection flow
      rates, regardless of tissue resistance. METHODS AND MATERIALS: Twenty adult
      subjects received bilateral palatal injections of local anesthetic in random
      sequence during the same appointment following topical anesthesia application.
      Pain response was measured by subjective self-report using a visual analogue
      scale, a quantified verbal descriptor scale, and a comparison to prior injection
      experience, as well as an operator's global assessment of the subject's pain
      response. Heart rate, as a physiologic indicator of pain response, was also
      recorded. RESULTS: All measurements of pain response were statistically less for
      the slow compared to the fast injection rate. No significant difference in mean
      heart rate, however, was demonstrated between the two flow rates. A slow,
      constant flow rate (161 sec/mL) of a 0.3 mL volume of local anesthetic solution
      was statistically less painful than a fast flow rate (29 sec/mL) during palatal
      injection. Contrary to the manufacturer's claim, the WLAS reduced but did not
      eliminate pain elicited by palatal injections in some patients.

PMID- 12074225
TI  - Evaluation of published clinical studies for reproducibility, comparability and
      adherence to evidence-based methods.
AB  - PURPOSE: To evaluate the "Materials and Methods" of long-term clinical studies in
      relation to documentation, reproducibility and comparability with and without
      employing the systematic methods of evidence-based medicine. MATERIALS AND
      METHODS: The "Materials and Methods" sections in 45 clinical long-term published
      studies of direct posterior resin-based composite restorations were evaluated for
      their use of systematic methods of evidence-based medicine. The search was
      limited to the years 1988-1997, using the key words "clinical
      study/evaluation/results/report, long-term, in vivo, posterior, Class I/II,
      composite, restoration". Special attention was directed to comparisons of the
      underlying documentation, descriptions of the operative techniques used, and
      their reproducibility. In addition, an evidence-based search was carried out
      using the Internet PubMed interface for MEDLINE, using identical synonyms, to
      identify studies with high levels of quality of evidence. Documentation,
      reproducibility, and comparability of "Materials and Methods" were also
      evaluated. RESULTS: Results revealed how difficult it is to interpret results
      based on tenuous premises, subjective standards, and inadequate study designs.
      Only one article could be identified when the search was limited to "humans" and
      "randomized clinical trials". None of the articles, even when fulfilling the
      highest quality of evidence, showed sufficient or satisfactory quality of
      reproducibility in their descriptions in Materials and Methods.

PMID- 12074226
TI  - Initial color change and color retention with a hydrogen peroxide bleaching
      strip.
AB  - PURPOSE: A randomized, double blind clinical trial was conducted to evaluate
      initial color improvement and post-treatment color retention following vital
      bleaching with a strip-based tooth whitening system. MATERIALS AND METHODS: After
      balancing for baseline color, 57 healthy adults were randomized to either
      whitening strips with a 5.3% hydrogen peroxide bleaching gel (Crest Whitestrips)
      or placebo strips without hydrogen peroxide. Maxillary and mandibular anterior
      teeth were treated twice daily for 30 minutes each over a 2-week period, and
      efficacy was measured objectively by comparing digital images of teeth collected
      at baseline, end-of-treatment (Week 2) and 6 months after treatment (Month 6).
      RESULTS: The whitening strip group experienced a highly significant (P< 0.0001)
      reduction in yellow of -2.0 deltab* units versus baseline and -1.95 deltab* units
      versus placebo, with similar results noted for the other color parameters in the
      study. Most of the initial color change remained at 6 months post-treatment, with
      the whitening strip group continuing to demonstrate highly significant (P<
      0.0001) improvements in tooth color relative to baseline and placebo. Age was
      found to significantly contribute to initial color improvement, with younger
      subjects experiencing a greater initial reduction in yellowness compared to older
      participants, but not to post-treatment color retention. The whitening strips
      were well tolerated, with minor tooth sensitivity and oral irritation
      representing the most common findings during treatment. There were no persistent
      or new treatment-related adverse events during the 6-month monitoring period.

PMID- 12074227
TI  - Morphological characterization of single bottle adhesives and vital dentin
      interface.
AB  - PURPOSE: To evaluate the in vivo interfacial relationship between four one-bottle
      adhesives and dentin. MATERIAL AND METHODS: Four one-bottle adhesives (Scotchbond
      1, Syntac SC, One-Step and Prime & Bond 2.1) were applied on flat dentin surfaces
      on human anterior teeth scheduled for extraction for dentures. A three-step
      adhesive system (Scotchbond Multi-Purpose) was used as a control. After adhesive
      application, a thin layer of composite was applied and light cured. The teeth
      were extracted immediately after resin curing. All samples were split fractured
      along their long axis. Half of the samples were deproteinized and decalcified at
      the interface in order to visualize the hybrid layer. The other halves were
      completely dissolved to observe the morphology of the resin tags. RESULTS: All
      the one-bottle adhesives produced hybrid layers and resin tags at the dentin
      resin interface. The three-step adhesive showed the same interfacial image but
      with a thicker hybrid layer and longer resin tags.

PMID- 12074228
TI  - Two-year clinical and SEM evaluation of glass-fiber-reinforced inlay fixed
      partial dentures.
AB  - PURPOSE: To clinically evaluate conservative fiber-reinforced composite inlay
      fixed partial dentures (IFPDs) bonded to inlay abutments. MATERIALS AND METHODS:
      Forty fiber-reinforced composite IFPDs were made for 29 patients. Restorations
      were manufactured with the composite Targis reinforced by Vectris prefabricated
      glass-fiber elements and were inserted with a high viscosity insertion technique.
      Forty bonded IFPDs were examined clinically after 1 year, and 25 after 2 years,
      using modified USPHS criteria. Twenty-five abutment inlays and 12 pontics were
      analyzed quantitatively by scanning electron microscopy SEM. Results were tested
      for statistical significance with ANOVA. RESULTS: Although most clinical criteria
      were rated "alpha", four IFPDs had to be replaced: two retainers debonded and two
      presented total delamination of veneering material from fiber framework. Two
      partial delaminations were repaired intraorally. No fractures of framework were
      observed. SEM marginal analysis of tooth-composite interface exhibited 96.5 +/-
      3.0% continuous margin at baseline, 91.0 +/- 5.7% at the 1-year and 89.6 +/- 5.2%
      at the 2-year recall. Decrease of marginal quality was statistically significant
      between baseline and 1 year (P= 0.001), but not between 1- and 2-year recalls.

PMID- 12074229
TI  - Cavity remaining dentin thickness and pulpal activity.
AB  - PURPOSE: To investigate pulpal injury by measuring odontoblast numbers, and pulp
      dentin repair activity by measuring reactionary dentin area, in relation to the
      remaining dentin thickness (RDT) of cavity preparations in 217 human teeth.
      MATERIALS AND METHODS: Cavities were restored with adhesive bonded composite,
      resin-modified glass-ionomer cement, zinc oxide-eugenol or calcium hydroxide
      materials. The teeth were extracted for orthodontic reasons between 20-381 days
      post-operatively, and odontoblast numbers and reactionary dentin area were
      analyzed histomorphometrically, and statistically using ANOVA. RESULTS:
      Reactionary dentin deposition was observed beneath cavities with a RDT above 0.5
      mm as well as beneath cavities with a RDT below 0.25 mm; however maximal
      reactionary dentin appeared to be beneath cavities with an a RDT between 0.5-0.25
      mm (P= 0.0001). The area of reactionary repair was also influenced by the choice
      of restoration material (P= 0.0385) from greatest to least; calcium hydroxide,
      composite, resin-modified glass-ionomer cement and zinc oxide-eugenol.
      Odontoblast numbers were maintained beneath cavities with a RDT above 0.25 mm,
      cavities placed closer to the pulp appeared to injure underlying odontoblasts,
      reducing their numbers (P= 0.0001). The choice of cavity restoration material
      also influenced the survival of underlying odontoblasts (P= 0.0061).

PMID- 12074230
TI  - Effect of light source and specimen thickness on the surface hardness of resin
      composite.
AB  - PURPOSE: To compare the Knoop hardness of different thicknesses of resin
      composite irradiated using either a plasma arc curing (PAC) light, or a quartz
      tungsten halogen (QTH) light. MATERIALS AND METHODS: A 2.5-mm diameter hole was
      drilled through the center of 2, 3, 4, and 5-mm thick discs of enamel and dentin.
      This hole was filled with either Filtek P60 or Prodigy Condensable composite and
      irradiated in bulk using: (a) a PAC light with an 8-mm, 470 nm light guide for 3
      seconds, (b) a QTH light with an 8-mm standard light guide for 40 seconds
      (QTH+S), or (c) a QTH light with a 13/8-mm Turbo light guide for 40 seconds
      (QTH+T). Immediately after irradiating the composite, the surface hardness was
      measured at the bottom and then the top. Hardness values were remeasured after 24
      hour and 7-day storage in water at 37 degrees C. The hardness values were
      compared using the Analysis of Variance for Repeated Measures and Least Squares
      Means test for multiple comparisons (LSM test) at P< 0.05. RESULTS: The power
      density delivered by each light was: PAC over 1999 mW/cm2, QTH+S 588 mW/cm2, and
      QTH+T 844 mW/cm2. Both the thickness of the composite and the light source had a
      significant effect on the hardness. Overall, using the QTH+T produced the highest
      hardness values and the PAC light the lowest values. For all 2-mm thick
      specimens, irrespective of the light source, the hardness values at the bottom
      were not significantly different from their top hardness values measured at the
      same time. For the 3-mm thick specimens using the QTH+T, the hardness values at
      the bottom of both composites were not significantly different from their top
      hardness values at all time intervals. For the 3-mm thick specimens using the
      QTH+S, the bottom hardness values were not significantly different from those at
      the top for P60 only, and only at 24 hours and 7 days, but not when measured
      immediately. For all the 4 and 5-mm thick specimens, the hardness values at the
      bottom were all significantly different from those at the top measured at the
      same time interval.

PMID- 12074231
TI  - Preservation-based approaches to restore posterior teeth with amalgam, resin or a
      combination of materials.
AB  - This review is a systematic assessment, from the literature, of the status quo of
      dental amalgam, resin-based composite and glass-ionomer restorations for carious
      lesions as it applies to new concepts, coupled with clinical research.
      Scientifically based and practical new materials and techniques are recommended
      to include in contemporary practice throughout the world. Clinical and laboratory
      studies which have been carried out in light of modern conservative principles,
      and in light of the current emphasis of treating dental caries as a disease
      process were reviewed and discussed. An approach to managing carious lesions
      based upon selected advantages of dental amalgam, resin-based composite and glass
      ionomer technology applied to what is termed "preservation-based" approaches to
      restoring teeth has been synthesized. Researched evidence contradicts the notion
      of "extension for prevention" in favor of maintaining sound tooth structure which
      would translate into more patients with healthy dentitions for entire lifetimes.

PMID- 12074232
TI  - Tips on preparing instruments for sterilization.

PMID- 12074233
TI  - Acquired vascular lesion of the lower lip.

PMID- 12074234
TI  - Fluoride release and caries inhibition associated with a resin-modified glass
      ionomer cement at varying fluoride loading doses.
AB  - PURPOSE: To measure, over time, the release of fluoride from a resin-modified
      glass-ionomer cement, loaded with different levels of fluoride, then to evaluate
      the adjacent dentin demineralization inhibition relative to these fluoride
      levels. MATERIALS AND METHODS: (Phase I) 25 standardized discs were fabricated
      from a non-fluoridated resin-based composite (control), resin-modified glass
      ionomer cement and resin-modified glass-ionomer cement loaded with sodium
      fluoride at 1%, 2% and 3% by weight fluoride. Fluoride release was evaluated over
      30 days. (Phase II) 50 restorations, from the materials listed in Phase I, were
      placed as Class V restorations in teeth, the teeth were acid-challenged, then
      dentin margins adjacent to restoration margins were evaluated for
      demineralization. RESULTS: As sodium fluoride additions increased, fluoride
      release increased. Evaluation of demineralization indicated the resin-modified
      glass-ionomer cement inhibited adjacent demineralization in a direct relationship
      with sodium fluoride concentration where 3% fluoride exhibited significantly less
      adjacent demineralization than all other groups; 2% and 1% fluoride exhibited
      significantly less adjacent demineralization than the non-loaded resin-modified
      glass-ionomer cement and non-fluoridated resin-based composite control (P< 0.05).

PMID- 12074235
TI  - Hock injuries in cattle kept in straw yards or cubicles with rubber mats or
      mattresses.
AB  - Hock damage is one of the most common traumatic injuries suffered by dairy cows,
      but most hock injuries should be avoidable. This study investigated the effect of
      housing system on the development of hock damage in first lactation Holstein
      heifers. After calving, 60 heifers were randomly allocated to either straw yards,
      cubicles with butyl rubber mats or cubicles with mattresses filled with chopped
      tyres. The hocks of these heifers were examined in the first week after calving
      (week 1) and in weeks 6, 12 and 26 of lactation. Hock damage was scored as either
      1 (hair loss only) or 2 (all other damage). Heifers housed in cubicles with mats
      had significantly worse lesions at week 26 than at week 1, while there was no
      change in heifers housed in cubicles with matresses, and heifers housed on straw
      had significantly lower lesion scores. Additionally, heifers with no lesions at
      calving were significantly more likely to develop lesions when kept on mats than
      heifers kept on straw or mattresses. These data suggest that replacing mats with
      mattresses in cubicles can result in a significant reduction in traumatic hock
      injury.

PMID- 12074236
TI  - Discriminant value of blood and urinary corticoids for the diagnosis of scrapie
      in live sheep.
AB  - The mean (sd) concentration of plasma 20beta-dihydrocortisol in 126 scrapie
      affected sheep was 5-5 (7.0) ng/ml compared with 1.1 (0.7) ng/ml in 52 healthy
      sheep. The mean (sd) concentration of creatinine in the urine of 93 scrapie
      affected sheep was 2.43 (1.56) microg/ml compared with 0.94 (0.86) pg/ml in 49
      healthy sheep and 1.10 (0-95) pg/ml in 25 sheep with other diseases. These
      discriminant analyses carried out on healthy and scrapie-affected sheep showed
      that plasma 20beta-dihydrocortisol and urinary creatinine were the best
      predictors of the disease, and classified correctly 98 per cent of healthy sheep
      and 82 per cent of scrapie-affected sheep.

PMID- 12074237
TI  - Clinical efficacy and pharmacokinetics of carprofen in the treatment of dogs with
      osteoarthritis.
AB  - Six medium to large breed dogs with osteoarthritis were treated with 2 mg/kg of
      racemic carprofen, mixed with their morning feed, daily for 28 days. The
      treatment significantly (P < 0.01) reduced their mean lameness score, measured on
      a visual analogue scale, and there was a trend (P = 0.11) for the peak vertical
      forces exerted on a forceplate to be increased in the most severely affected
      limb. The plasma concentration-time relationships of the S(+) and R(-)
      enantiomers were studied for 24 hours after the first dose and after seven days
      and 28 days. There were no significant differences between the mean
      pharmacokinetic parameters measured on the three occasions, suggesting that
      carprofen was not accumulated and that tolerance to the drug did not develop.
      Although the pharmacokinetic parameters of the S(+) and R(-) enantiomers were
      generally very similar, there were wide variations both between and within dogs.

PMID- 12074238
TI  - Identification of Escherichia coli O157:H7-strains from pigs with postweaning
      diarrhoea and amplification of their virulence marker genes by PCR.
AB  - Escherichia coli isolated from pigs with postweaning diarrhoea were examined by
      PCR for the presence of the O157 rfb gene responsible for the biosynthesis of E
      coli O157 lipopolysaccharide. Among the 372 isolates tested, 38 (10.2 per cent)
      were of the O157 serogroup, but none of these possessed the H7 determinant.
      Further analysis of the E coli O157 isolates revealed that seven of them had the
      genes responsible for the production of Shiga toxin 1 and eaeA intimin, four
      other strains had genes responsible for the production of Shiga toxin 2, and four
      other strains were positive for the enterohaemolysin gene.

PMID- 12074239
TI  - Presence of Salmonella infections in freshwater turtles.

PMID- 12074240
TI  - Flavobacterium columnare (Flexibacter columnaris) associated with severe gill
      necrosis in koi carp (Cyprinus carpio L).

PMID- 12074241
TI  - Grass sickness in horses in southern Chile.

PMID- 12074242
TI  - Inflammatory pseudotumour of the spleen in a dog.

PMID- 12074243
TI  - Contagious bovine pleuropneumonia and vaccine strain T1/44.

PMID- 12074244
TI  - Supply of POMs.

PMID- 12074245
TI  - Veterinary nurse training.

PMID- 12074247
TI  - Archaeological expedition.

PMID- 12074246
TI  - Impact of FMD on the environment.

PMID- 12074248
TI  - RCVS Council elections.

PMID- 12074249
TI  - Selenocompounds in plants and animals and their biological significance.
AB  - There are several selenocompounds in tissues of plants and animals. Selenate is
      the major inorganic selenocompound found in both animal and plant tissues.
      Selenocysteine is the predominant selenoamino acid in tissues when inorganic
      selenium is given to animals. Selenomethionine is the major selenocompound found
      initially in animals given this selenoamino acid, but is converted with time
      afterwards to selenocysteine. Selenomethionine is the major selenocompound in
      cereal grains, grassland legumes and soybeans. Selenomethionine can also be the
      major selenocompound in selenium enriched yeast, but the amount can vary markedly
      depending upon the growth conditions. Se-methylselenocysteine is the major
      selenocompound in selenium enriched plants such as garlic, onions, broccoli
      florets and sprouts, and wild leeks.

PMID- 12074250
TI  - Comparative effects of dietary corn oil, safflower oil, fish oil and palm oil on
      metabolism of ethanol and carnitine in the rat.
AB  - OBJECTIVE: This study was launched to determine comparative effects of corn oil
      (CO), safflower oil (SO), fish oil (FO) and palm oil (PO) on carnitine status and
      ethanol metabolism in rats. METHODS: Twenty-four male Sprague-Dawley rats (300 g
      bw) were randomly divided into four groups (n = 6) and fed a semisynthetic diets
      containing fat as oils listed above. Blood and 24 hour urine samples were
      collected before and after dietary treatment and acute ethanol administration.
      Samples were analyzed for blood-ethanol concentration (BEC) and carnitine
      species. RESULTS: The diets containing FO and PO retarded ethanol metabolism
      compared to the diets containing CO and SO. The effect of these dietary fats on
      carnitine species in plasma and urine was varied before and after dietary
      treatment and following a single oral ethanol dose. The liver carnitine content
      was higher in the PO group after dietary and ethanol treatment. CONCLUSION: It is
      concluded that attenuation of ethanol clearance was related to unique fatty acid
      makeup of the oils that in part may be attributed to the composite ratio of
      saturated to unsaturated fatty acids in the oils.

PMID- 12074251
TI  - Calcium effects on phosphorus absorption: implications for the prevention and co
      therapy of osteoporosis.
AB  - OBJECTIVE: To evaluate the effect of calcium intake on absorption of dietary
      phosphorus, with special reference to typical calcium intakes and to those likely
      to be encountered in prevention and treatment of osteoporosis. SETTING: Two
      academic health sciences centers; inpatient metabolic research unit. METHODS:
      Evaluation of calcium and phosphorus balance data obtained in two data sets, the
      first, 543 studies of healthy women aged 35-65, and the second, 93 men and women
      aged 19-78; development of multiple regression models predicting fecal phosphorus
      (the complement of net absorbed phosphorus); data from the two centers analyzed
      separately as a check on the consistency of the findings. RESULTS: Mean net
      absorption of phosphorus was 60.3% (+/- 18.1) for data set 1 and 53.0% (+/-9.4)
      for data set 2. Just two variables, fecal calcium and diet phosphorus, were
      positively and independently associated with fecal phosphorus. These variables
      explained 73% of the variance in fecal phosphorus in data set 1 and 33% in data
      set 2. Fecal calcium alone explained the lion's share of the relationship. The
      coefficients of the fecal calcium term in the models fitted to the data were
      0.332+/-0.022 and 0.155+/-0.039, for data sets I and 2, respectively. Adjusting
      for the relationship between fecal calcium and calcium intake and using the
      parameters of the larger data set, it follows that each increase in calcium
      intake of 0.5 g (12.5 mmol) decreases phosphorus absorption by 0.166 g (5.4
      mmol). CONCLUSIONS: As calcium intake increases without a corresponding increase
      in phosphorus intake, phosphorus absorption falls and the risk of phosphorus
      insufficiency rises. Intakes with high Ca:P ratios can occur with use of
      supplements or food fortificants consisting of non-phosphate calcium salts. Older
      patients with osteoporosis treated with current generation bone active agents
      should receive at least some of their calcium co-therapy in the form of a calcium
      phosphate preparation.

PMID- 12074252
TI  - Body composition of newborn twins: intrapair differences.
AB  - OBJECTIVE: To measure body composition in newborn twins and to test the
      hypothesis that differences in body weights between twins are reflected
      proportionally by their differences in various components of body composition.
      METHODS: 48 pairs of newborn twins delivered at a tertiary teaching hospital had
      dual energy x-ray absorptiometry (DXA) body composition measurement for bone
      mineral content (BMC), lean and fat mass (LM, FM). Data analyzed with regression
      and analysis of variance. RESULTS: Body weight, BMC, LM and FM increased with
      increased gestational age (p < 0.001). The percent difference in BW between each
      twin pair was significantly correlated with percent difference in BMC, LM, and FM
      (p < 0.001). However, mean (+/- SD) percent difference in body weight (14.3+/
      10.0%) was significantly lower (p < 0.001) than FM (26.0+/-15.0%) but was not
      significantly different from LM (13.4+/-9.0%) or BMC (15.9+/-11.6%). CONCLUSION:
      In newborn twins, body weight and body composition varies with gestational age.
      For any twin pair, a difference in body weight was correlated with but not
      proportional to differences in individual components of body composition.

PMID- 12074253
TI  - Pre-menopausal women, classified as hypo- or hyperresponders, do not alter their
      LDL/HDL ratio following a high dietary cholesterol challenge.
AB  - BACKGROUND: Cholesterol is the dietary component that has elicited the most
      public interest in conjunction with coronary heart disease. However, the impact
      of excess dietary cholesterol intake on plasma cholesterol levels cannot be
      accurately predicted; therefore, its role in disease progression is not
      straightforward. Individual response variation can be due to factors such as
      ethnicity, hormonal status, obesity and genetic predisposition. OBJECTIVE: The
      purpose of this study was to evaluate the differences that occur within the
      plasma compartment of normolipidemic pre-menopausal women, classified based on
      their response to a high dietary cholesterol challenge. DESIGN: We recruited 51
      pre-menopausal women (29 Caucasian and 22 of Hispanic origin) aged 18 to 49 years
      with initial plasma cholesterol concentrations ranging from 3.62 to 5.17 mmol/L.
      Using a cross-over research design, women were randomly allocated to an egg (640
      mg additional dietary cholesterol per day) or placebo group (0 mg additional
      dietary cholesterol per day) initially, and the two 30 day periods were separated
      by a three-week washout. RESULTS: An initial evaluation of the ethnicity effects
      revealed elevations in both plasma LDL-C (p < 0.0001) and HDL-C (p < 0.001)
      concentrations in both Hispanics and Caucasians during the high dietary
      cholesterol period. However, these increases were not accompanied by a change in
      the LDL/HDL ratio. Subjects were then classified as hypo- (< 0.05 mmol/L increase
      in total plasma cholesterol per each additional 100 mg of dietary cholesterol
      consumed per day) or hyper-responders (> or =0.06 mmol/L increase in total blood
      cholesterol per each additional 100 mg of dietary cholesterol consumed per day),
      based on their reaction to the additional dietary cholesterol provided. Hypo
      responders did not experience an increase in LDL-C or HDL-C during the egg
      period, while both lipoproteins were elevated in hyper-responders. However, the
      LDL/HDL ratio, an important parameter of coronary heart disease risk, was
      maintained for all subjects during the egg period independent of response.
      Furthermore, hyper-responders had higher concentrations of apo C-III (p < 0.001),
      apo B (p < 0.001) and cholesterol ester transfer protein (CETP) (p < 0.05) during
      this period. CONCLUSION: These data revealed that excess dietary cholesterol does
      not increase the risk of developing an atherogenic lipoprotein profile in pre
      menopausal women, regardless of their response classification. Although the
      addition of 640 mg of cholesterol to the diet did result in an increase in plasma
      cholesterol in hyperresponders, the LDL/HDL ratio was maintained. This result,
      accompanied by increases in CETP activity, leads to the speculation that hyper
      responders may process the excess cholesterol in the plasma compartment through
      an enhancement of the reverse cholesterol transport pathway. With this mechanism
      identified, further measurement of additional parameters is needed to verify this
      conclusion.

PMID- 12074254
TI  - Effect on body weight of replacing dietary fat with olestra for two or ten weeks
      in healthy men and women.
AB  - OBJECTIVE: To examine in two separate studies the effects of replacing dietary
      fat with Olestra on body composition and weight change in healthy young men and
      women. METHODS: Ten healthy, lean young men participated in Study One that was a
      22-day single blind, within-subject design. After a control diet (40% fat) for
      eight days Study One subjects received an Olestra-substituted diet (31%
      metabolizable fat) for 14 days. Study Two was a randomized parallel-arm clinical
      trial with 15 healthy, lean and overweight young women. These subjects were
      randomly assigned to receive a control diet (40% fat), an Olestra-containing diet
      (31% metabolizable fat) or a reduced-fat diet (31% fat) for 10 weeks. All foods
      were provided to the subjects, and energy intakes were not restricted. The
      primary endpoint in both studies was change from baseline in body weight. In
      Study Two, body composition was measured by dual energy x-ray absorptiometry. In
      both studies, food intake and nutrient compensation were assessed. RESULTS: In
      Study One fat substitution by Olestra resulted in a significant 1.7 kg weight
      loss from baseline. In Study Two, change in body weight and body fat from
      baseline were statistically significant in all groups, but the group with Olestra
      lost significantly more weight from baseline (-5.0 kg) than the other two groups.
      In Study One there was partial compensation for the decreased energy intake,
      while in Study Two, compensation was seen only for those on the reduced-fat diet.
      CONCLUSION: Replacement of 1/3 of dietary fat with Olestra in periods of up to 10
      weeks results in weight loss in men and women.

PMID- 12074255
TI  - A comparison of low-carbohydrate vs. high-carbohydrate diets: energy restriction,
      nutrient quality and correlation to body mass index.
AB  - OBJECTIVES: To evaluate free-living adults' diets that ranged from very low to
      high amounts of carbohydrate for their energy content, nutritional quality and
      correlation to Body Mass Index. METHODS: Adults ages 19 years and older, who had
      complete dietary intake data on day-1 of the USDA's 1994 to 1996 Continuing
      Survey of Food Intakes by Individuals (CSFII 1994-1996), were divided into four
      groups--very low, low, moderate and high carbohydrate--based on the percent total
      energy from carbohydrate. Mean energy, nutrient, food intakes and Body Mass Index
      values were compared among the groups. SUDAAN software package was used for the
      data analysis and pair-wise mean comparisons (p < 0.05). RESULTS: The high
      carbohydrate diet was lower in energy and energy density (number of kilocalories
      per gram of total amount of food consumed) than the other three diets.
      Macronutrient composition varied significantly among all the four groups.
      Nutrient density (amount of nutrient per 1,000 kilocalories of energy consumed)
      of vitamin A, carotene, vitamin C, folate, calcium, magnesium and iron increased
      and that of vitamin B12 and zinc decreased with an increase in the percent total
      energy from carbohydrate. The high-carbohydrate group ate more of low-fat foods,
      grain products and fruits. This group also had the lowest sodium intake. Adults
      eating a high-carbohydrate diet are more likely to have Body Mass Index values
      below 25. CONCLUSION: A study of diets of free-living adults in the U.S. showed
      that diets high in carbohydrate were both energy restrictive and nutritious and
      may be adopted for successful weight management.

PMID- 12074256
TI  - Effect on body weight of a free 76 Kilojoule (320 calorie) daily supplement of
      almonds for six months.
AB  - OBJECTIVE: Regular nut consumption is associated with lower rates of heart
      attack. However, as nuts are fatty foods, they may in theory lead to weight gain,
      although preliminary evidence has suggested otherwise. We tested the hypothesis
      that a free daily supplement (averaging 76 kJ) of almonds for six months, with no
      dietary advice, would not change body weight. METHODS: Eighty-one male and female
      subjects completed the randomized cross-over study. During two sequential six
      month periods, diet, body weight and habitual exercise were evaluated repeatedly
      in each subject. Almonds were provided only during the second period. The design
      was balanced for seasonal and other calendar trends. RESULTS: During the almond
      feeding period, average body weight increased only 0.40 (kg) (p approximately
      0.09). The weight change depended on baseline BMI (p = 0.05), and only those
      initially in the lower BMI tertiles experienced small and mainly unimportant
      weight gains with the almonds. We estimated that 54% (recalls) or 78% (diaries)
      of the extra energy from almonds was displaced by reductions in other foods. The
      ratio unsaturated/saturated dietary fat increased by 40% to 50% when almonds were
      included in the diet. CONCLUSION: Incorporating a modest quantity (76 kJ) of
      almonds in the diet each day for six months did not lead on average to
      statistically or biologically significant changes in body weight and did increase
      the consumption of unsaturated fats. Further studies are necessary to evaluate
      longer term effects, especially in men.

PMID- 12074257
TI  - Determination of macronutrients, by chemical analysis, of home-prepared milk
      feeding bottles and their contribution to the energy and protein requirements of
      infants from high and low socioeconomic classes.
AB  - OBJECTIVES: To determine the macronutrients composition of home-prepared milk
      feeding bottles, by chemical analysis, and assess their contribution to the
      energy and protein requirements of children under two years of age from high
      (HSE) and low (LSE) socioeconomic classes. METHODS: 72 samples were analyzed for
      energy density and protein, fat and carbohydrate content: 41 from the LSE group
      and 31 from the HSE group. The assessment of the percentages of the energy and
      protein requirements met by the consumption of the milk bottles was calculated as
      follows: the energy and protein per 100 mL obtained through chemical analysis
      were multiplied by the volume consumed at each feeding, then by the number of
      feedings per day, the results divided by the energy and protein requirements and
      multiplied by 100. Energy and protein requirements were those recommended by the
      FAO/WHO/UNU Committee and the Food and Nutrition Board. The children's weight-for
      age index was assessed. RESULTS: Unmodified cow's milk was largely consumed by
      both groups. The addition of sugar and other ingredients to the milk was
      significantly higher in the LSE group. Moisture, protein and fat content were
      lower in the LSE group, whereas carbohydrate and energy content were higher. The
      percentages of energy and protein requirements provided by feeding bottles were
      higher in the LSE group. Children in the LSE group had lower z-scores for weight
      for-age. CONCLUSIONS: Differences in the preparation practices led to differences
      in the chemical results. The feeding bottles in the LSE group were high in
      energy, due to the addition of sugar and cereals to the milk in the bottle. The
      milk feeding bottles were an important weaning food providing more than 50% and
      100% of the children's energy and protein requirements, respectively. The
      children's weight-for-age index was within the normal limits.

PMID- 12074258
TI  - Assessing health status and quality-of-life instruments: attributes and review
      criteria.
AB  - The field of health status and quality of life (QoL) measurement - as a formal
      discipline with a cohesive theoretical framework, accepted methods, and diverse
      applications--has been evolving for the better part of 30 years. To identify
      health status and QoL instruments and review them against rigorous criteria as a
      precursor to creating an instrument library for later dissemination, the Medical
      Outcomes Trust in 1994 created an independently functioning Scientific Advisory
      Committee (SAC). In the mid-1990s, the SAC defined a set of attributes and
      criteria to carry out instrument assessments; 5 years later, it updated and
      revised these materials to take account of the expanding theories and
      technologies upon which such instruments were being developed. This paper offers
      the SAC's current conceptualization of eight key attributes of health status and
      QoL instruments (i.e., conceptual and measurement model; reliability; validity;
      responsiveness; interpretability; respondent and administrative burden; alternate
      forms; and cultural and language adaptations) and the criteria by which
      instruments would be reviewed on each of those attributes. These are suggested
      guidelines for the field to consider and debate; as measurement techniques become
      both more familiar and more sophisticated, we expect that experts will wish to
      update and refine these criteria accordingly.

PMID- 12074259
TI  - Meaningful change in cancer-specific quality of life scores: differences between
      improvement and worsening.
AB  - INTRODUCTION: There has been increased recent attention to the clinical
      meaningfulness of group change scores on health-related quality of life (HRQL)
      questionnaires. It has been assumed that improvements and declines of comparable
      magnitude have the same meaning or value. METHOD: We assessed 308 cancer patients
      with the Functional Assessment of Cancer Therapy (FACT) and a Global Rating of
      Change. Patients were classified into five levels of change in HRQL and its
      dimensions based upon their responses to retrospective ratings of change after 2
      months: sizably worse, minimally worse, no change, minimally better, and sizably
      better. Raw score and standardized score changes on the FACT-G subscales and
      total score were then compared across different categories of patient-rated
      change. RESULTS: The relationship between actual FACT change scores and
      retrospective ratings of change was modest but usually statistically significant
      (r: 0.07 to 0.35). Change scores associated with each retrospective rating
      category were evaluated to determine estimates of meaningful difference. Patients
      who reported global worsening of HRQL dimensions had considerably larger change
      scores than those reporting comparable global improvements. Although related to a
      ceiling effect, this remained true even after removing cases that began near the
      ceiling of the questionnaire. DISCUSSION: Relatively small gains in HRQL have
      significant value. Comparable declines may be less meaningful, perhaps due to
      patients' tendency to minimize personal negative evaluations about one's
      condition. This has important implications for the interpretation of the
      meaningfulness of change scores in HRQL questionnaires. Factors such as
      adaptation to disease, response shift, dispositional optimism and the need for
      signs of clinical improvement may be contributing to the results and should be
      investigated in future studies.

PMID- 12074260
TI  - Multidimensional scaling as a tool for analysing quality of life data.
AB  - Multidimensional scaling (MDS) is introduced and discussed as a graphical method
      to complement conventional descriptive and confirmatory methods in the validation
      and analysis of quality of life (QOL) data. An outline of M DS as a statistical
      technique is given, and its application in the context of QOL research is
      described. The use of MDS is then illustrated in an example based on a study of
      300 cancer survivors who completed the functional assessment of cancer therapy
      general (FACT-G) and the EORTC core quality of life questionnaire (QLQ-C30). The
      correlational structure of the two widely used QOL instruments is investigated by
      means of MDS, and differences between the two questionnaires are elaborated.
      Finally, the merits and drawbacks of MDS are discussed in the specific context of
      the example and in the general framework of QOL research.

PMID- 12074261
TI  - The health-related quality of life and survival of small-cell lung cancer
      patients: results of a companion study to CALGB 9033.
AB  - The purposes of this study were 2-fold: to evaluate the impact of the schedule
      dependency of etoposide (3-day IV short course vs. a 21-day oral prolonged
      course) with cisplatin on the quality of life of small-cell lung cancer (SCLC)
      patients; and to examine the effect of baseline quality of life variables on long
      term survival, after adjustment for known demographic and clinical prognostic
      factors. Participants were 70 patients enrolled in the cancer and leukemia group
      B (CALGB) protocol 9033. Quality of life was assessed at baseline, 6 and 12 weeks
      by: the EORTC QLQ-30, the Centers for epidemiology studies--Depression short
      form, the medical outcomes study (MOS) social support questionnaire, and a scale
      of sleep quality. Contrary to expectations, study results suggested no
      significant differences in the patients' life quality and treatment response
      based on whether they received etoposide in a 3-day IV vs. a 21-day oral regimen.
      The use of the baseline variables in predicting overall survival indicated that
      patients who were non-white and with liver involvement had decreased survival.
      Brain involvement, being male, and higher depressive symptoms were also found to
      be borderline significant in predicting decreased survival in this patient
      population.

PMID- 12074262
TI  - The influence of cardiovascular disease on quality of life in type 2 diabetics.
AB  - BACKGROUND AND AIMS: In type 2 diabetes mellitus, disease-related complications
      have a considerable effect on the quality of life. We studied the influence of
      cardiovascular disease on quality of life in type 2 diabetic patients in a
      longitudinal design. We also studied whether quality of life in any way predicts
      the manifestation of cardiovascular disease. MATERIALS AND METHODS: A prospective
      cohort study from April 1996 to October 1999. In 1996 and 1999 all known type 2
      diabetics from the population of Urk, the Netherlands, were invited by their
      general practitioners (GPs) for extensive check-up. In both years quality of life
      was assessed using the generic RAND-36 and the disease-specific Diabetes Health
      Profile (DHP). In the intermediate period, cardiovascular morbidity and mortality
      were registered by the GPs. RESULTS: In 1996, 281 patients were examined and 248
      (88.3%) persons completed the questionnaires. After 3 years 189 persons (67.3%)
      were re-examined and 161 (85.2%) handed in the questionnaire. When compared to
      diabetics without cardiovascular disease, diabetics with cardiovascular disease
      had a lower quality of life. Multiple regression analysis showed that contracting
      cardiovascular disease negatively affects the RAND-36 dimensions 'social
      functioning', 'vitality' and 'health change'. Cox's regression analysis showed a
      negative relation between the RAND-36 dimensions 'physical functioning', and time
      to the manifestation of cardiovascular disease. The DHP appeared not to be
      suitable to measure quality of life in relation to cardiovascular disease.
      CONCLUSIONS: In type 2 diabetics, cardiovascular disease has a negative effect on
      quality of life. A decreased quality of life is associated with a short-term
      manifestation of cardiovascular disease.

PMID- 12074263
TI  - Construction and validation of a fatigue impact scale for daily administration (D
      FIS).
AB  - The fatigue impact scale (FIS) was developed previously as a symptom-specific
      profile measure of health-related quality of life (HRQoL) for use in medical
      conditions in which fatigue is a prominent chronic symptom. Thus, it was not
      developed to be a responsive measure of daily changes in fatigue. This study
      describes the development and initial validation of an adaptation of the FIS for
      daily use. Items for the daily fatigue impact scale (D-FIS) were selected from
      the pool of original FIS items through Rasch analyses of existing data. The
      reduced-item FIS was administered to a sample of 93 subjects with flu-like
      illness, 25 of whom were followed for a 21-day period. Rasch analyses were used
      to further reduce the scale to a minimum number of items that represented a
      unidimensional measure of self-reported fatigue impact. This 8-item D-FIS
      demonstrated good relations to flu symptom ratings and to other general health
      ratings. It also proved to be a responsive measure of change in reported fatigue
      impact for subjects who were followed longitudinally. This initial validation
      study indicates that the D-FIS has considerable promise as a valid measure of the
      subjective daily experience of fatigue.

PMID- 12074265
TI  - Gender differences in the symptoms and physical and mental well-being of
      dyspeptics: a population based study.
AB  - PURPOSE: To compare women and men with dyspepsia in terms of symptoms, physical
      and mental well-being and the relationships between individual symptoms and well
      being. METHODS: A cross-sectional random telephone survey of 2300 Australians
      identified 748 people with dyspepsia who were interviewed regarding the number,
      types and severity of symptoms and physical (PCS) and mental well-being (MCS)
      measured by the SF-12. RESULTS: There were no significant gender differences in
      number or average severity of symptoms. Bloating, nausea, and early satiety were
      significantly more frequent among women; food regurgitation and heartburn in men.
      Dyspeptics (PCS = 47.1, MCS = 46.0) had poorer physical (p < 0.001) and mental
      well-being (p < 0.001) than did non-dyspeptics (PCS = 53.5, MCS = 55.3). Among
      dyspeptics, women (PCS = 46.4, MCS = 44.7) had poorer physical (p < 0.05) and
      mental well-being (p < 0.001) than males (PCS = 47.9, MCS = 47.5). Some symptoms
      were associated with low well-being for both sexes e.g. nausea. For women
      retching was related to poor physical well-being, and food regurgitation,
      dysphagia. bloating and epigastric pain to poor mental well-being. Among men
      epigastric pain and heartburn were associated with poor physical well-being, acid
      regurgitation with poor mental well-being, and vomiting with both. CONCLUSIONS:
      Dyspeptics report poorer physical and mental well-being than do non-dyspeptics.
      The difference between groups is greater for mental well-being, especially among
      women. Both physical and social factors may contribute to gender differences.

PMID- 12074264
TI  - Validity and responsiveness of the euroqol as a measure of health-related quality
      of life in people enrolled in an AIDS clinical trial.
AB  - OBJECTIVE: Brief utility measures are needed in clinical trials in addition to
      existing descriptive measures of health-related quality of life (HRQOL). We
      examined the reliability and validity of the EuroQol (EQ-SD) and MOS-HIV and
      their responsiveness to HIV-related clinical events. METHODS: Subjects with
      advanced HIV disease (CD4 < 100) were enrolled in a randomized trial for CMV
      prophylaxis (n = 990). The EQ-5D includes a weighted sum of five domains (EQ-5D
      Index) and a visual analog scale (EQ-VAS). The MOS-HIV has 10 subscales and
      physical (PHS) and mental health summary scores (MHS). Construct validity of the
      EQ-5D was tested based on hypothesized relationships to subscales of the MOS-HIV.
      Relative precision and responsiveness to adverse experiences and opportunistic
      infections (Ols) were compared for the two instruments. RESULTS: Mean age of the
      patients was 38, 94% were male, 80% white, and 7% had injected drugs. Mean
      baseline scores for EQ-5D Index and EQ-VAS were 0.80 and 76.0, respectively, 28
      and 4% reported maximum scores. Mean MOS-HIV subscales score ranged from 55
      (role) to 84 (cognitive); mean PHS and MHS were 47.4 and 49.5, respectively.
      Correlations between MOS-HIV subscales and EQ-5D Index ranged from 0.45 (role) to
      0.63 (pain); correlations with EQ-VAS ranged from 0.33 (cognitive) to 0.66
      (health perceptions). Correlations between MOS-HIV PHS and MHS with EQ-5D Index
      were 0.61 and 0.58; and with EQ-VAS, 0.57 and 0.60, respectively. Responsiveness
      to adverse experiences was highest for MOS-HIV pain and PHS (effect sizes = 0.9
      and 0.4); pain had the highest relative precision (2.4) for adverse experiences:
      EQ-VAS had the greatest relative precision (1.6) for developing an OI.
      CONCLUSION: In these patients with advanced HIV disease. EQ-5D showed good
      construct validity, but there may be a ceiling effect for its EQ-5D Index
      component. EQ-5D was less responsive to adverse events than the MOS-HIV. However,
      the EQ-VAS was most sensitive to developing an OI and is likely to be a useful
      measure of HRQOL for generating QALYs in cost-utility studies involving patients
      with advanced HIV disease.

PMID- 12074266
TI  - Clinical importance of endothelial function in arteriosclerosis and ischemic
      heart disease.
AB  - The vascular endothelium is a dynamic endocrine organ that regulates vascular
      tone, local homeostasis, and the fibro-inflammatory-proliferative process. These
      responses are mediated by various substances released from the endothelium in
      response to physiologic stimuli, including prostacyclin, endothelin and, most
      importantly, nitric oxide (NO). NO mediates vasodilation and inhibits platelet
      aggregation, thrombus formation, expression of adhesion molecules and chemokines
      for leukocytes, and oxidative stress. It also attenuates growth and proliferation
      of vascular smooth muscle cells. Risk factors for atherosclerosis, such as
      hypercholesterolemia, hypertension, diabetes and cigarette smoking, impair
      endothelial function, which leads to atherosclerosis and results in ischemic
      manifestations such as acute coronary syndrome and stroke. Thus, therapeutic
      intervention aimed at increasing NO bioavailability by statins or angiotensin
      converting enzyme inhibitors might improve patient prognosis. Vascular
      endothelial function is an important and clinically relevant therapeutic target
      for cardiovascular disease.

PMID- 12074267
TI  - Myocardial ischemia during percutaneous transluminal coronary angioplasty in
      patients with rich collateral circulation of the target lesion.
AB  - Although it is commonly believed that ischemia does not develop during coronary
      intervention in patients with rich collateral circulation to the target vessel,
      ST changes are often observed, the study group comprised 40 consecutive patients
      who underwent elective percutaneous coronary angioplasty and who had rich
      collateral vessels to the target lesions. None had side branches in the target
      vessel that would be occluded by the angioplasty balloon. During the
      intervention, the 12-lead electrocardiogram was monitored for any change in the
      ST-T segment and 13 (32.5%) showed significant ST changes. Of these, 3 had ST
      changes with every balloon inflation and the remaining 10 patients had ST changes
      with the second or subsequent inflations. Myocardial ischemia caused by balloon
      inflation is not uncommon during coronary angioplasty in patients with rich
      collaterals to the target vessel. The collateral circulation may stop functioning
      very early after improvement in the forward flow of the target vessel.

PMID- 12074269
TI  - Triple arterial coronary revascularization using the radial artery and bilateral
      internal mammary arteries versus the gastroepiploic artery and bilateral internal
      mammary arteries.
AB  - Arterial grafts are frequently used in modern coronary artery bypass grafting
      (CABG) and the benefit of the 2 internal mammary arteries (IMA) has already been
      established. However, the choice of the third arterial conduit, in addition to
      the IMA, is controversial. We have retrospectively analized perioperative and the
      follow-up results of patients who underwent CABG with triple arterial bypass
      using either the radial artery (RA) or the gastroepiploic artery (GEA) in
      conjunction with the bilateral IMA (BIMA). Between December 1995 and June 2001,
      1,516 consecutive isolated CABG operations were performed at Shin-Tokyo Hospital.
      Among them the RA and BIMA were used in 96 patients (78 males, 18 females; mean
      age, 63.2+/-6.7 years, group R), and the GEA and BIMA in 123 patients (101 males,
      22 females; mean age, 61.0+/-11.6 years, group G). Their perioperative and follow
      up data were studied. The preoperative risk factors were similar between the 2
      groups, except that there were significantly fewer patients with renal
      dysfunction in group R. The surgical results did not differ between the 2 groups;
      however, the GEA was more commonly used for revascularization of the right
      coronary artery, while the RA was used for the diagonal, circumflex or right
      coronary arteries. Surgical mortality and morbidity rates were not significantly
      different. During the follow-up period of 2.3+/-1.6 years, the event-free rates
      as well as the survival rates were not significantly different. CABG with either
      the RA or the GEA in conjunction with the BIMA can be performed safely. The
      surgical results as well as the follow-up results were acceptable and no
      significant differences between the 2 groups were observed.

PMID- 12074268
TI  - Prognostic value of repeated 123I-metaiodobenzylguanidine imaging in patients
      with dilated cardiomyopathy with congestive heart failure before and after
      optimized treatments--comparison with neurohumoral factors.
AB  - The present study was undertaken to assess whether repeated measurement of
      cardiac 123I-metaiodobenzylguanidine (MIBG) imaging parameters before and after
      optimized treatments is useful for predicting the prognosis of patients with
      congestive heart failure (CHF) resulting from dilated cardiomyopathy (DCM). The
      subjects were 85 consecutive patients with DCM who had a left ventricular
      ejection fraction (LVEF) of less than 45%. The MIBG and the concentrations of
      neurohumoral factors were measured at baseline and after 6 months of optimized
      treatments. Cox proportional hazards analysis was performed to assess the various
      parameters before and after treatment. Twenty-three patients had a cardiac event
      (12 died; 11 hospitalized) during a mean follow-up period of 2 years. Although
      there was no difference between the baseline heart to mediastinum (H/M) ratio
      measured by MIBG between survivors and nonsurvivors, the H/M ratio was
      significantly decreased in nonsurvivors after 6 months. Multivariate analysis
      revealed that a high plasma concentration of brain natriuretic peptide level
      after 6 months (p=0.0049) and absolute changes in the H/M ratio (p=0.0046) were
      independent predictors of mortality. Comparison of the H/M ratio on MIBG imaging
      before and after optimized additional treatment provided useful information for
      predicting mortality and was independent of clinical and neurohumoral factors
      previously shown to be associated with poor prognosis in patients with DCM.

PMID- 12074270
TI  - Clinical significance of the dispersion of the activation--recovery interval and
      recovery time as markers for ventricular fibrillation susceptibility in patients
      with Brugada syndrome.
AB  - Brugada syndrome (BS) is associated with sudden cardiac death and the markers for
      ventricular fibrillation (VF) remain unclear, so the activation-recovery interval
      (ARI) dispersion and recovery time (RT) dispersion were investigated as possible
      markers in 20 subjects with BS (BS group) and 22 healthy individuals (H group).
      The 20 BS subjects were divided into 8 cases with documented VF (BS-VF group), 3
      of which had recurrences, and 12 without (BS-N group). The corrected dispersion
      measurements from the standard 12-lead ECG of the QT interval (QTcd), ARI (ARIcd)
      and RT (RTcd) were compared among the groups. There were significant differences
      noted between the BS-VF and BS-N groups for the ARIcd and the RTcd, but not for
      the QTcd. Further, there were critical differences, 150 ms(1/2), observed for the
      ARIcd and RTcd, and these were associated with a prolongation of the maximum ARI
      or RT, shortening of the minimum ARI or RT, and prolongation only of the maximum
      QT for the QTcd. Susceptibility to VF may be predicted by the ARIcd or RTcd in
      BS.

PMID- 12074271
TI  - Double-blind placebo-controlled trial of aprindine and digoxin for the prevention
      of symptomatic atrial fibrillation.
AB  - A multicenter, placebo-controlled, randomized, double-blind trial compared the
      preventive effect of aprindine and digoxin on the recurrence of atrial
      fibrillation (AF) with placebo, and also compare the effectiveness of these 2
      drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent
      AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40
      mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis
      every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47
      were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month
      follow-up, the Kaplan-Meier estimates of the percentage of patients remaining
      free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%,
      29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from
      the start of follow-up, freedom from recurrence was significantly more prevalent
      in the aprindine group than in the placebo group (p=0.0414), but there was no
      significant difference between the digoxin and placebo groups. The rate of
      adverse events was similar in the 3 groups. In conclusion, neither aprindine nor
      digoxin had a significant effect on preventing relapse of symptomatic AF;
      however, recurrence of AF occurred later with aprindine than with placebo or
      digoxin.

PMID- 12074272
TI  - Long-term prognosis of patients with mildly dilated cardiomyopathy.
AB  - The long-term prognosis of patients with mildly dilated cardiomyopathy (MDCM) was
      investigated in 21 patients. MDCM was defined as left ventricular ejection
      fraction < or = 40% and left ventricular end-diastolic volume < or = 120 ml/m2 by
      left ventriculography. During a follow-up period of 6.8+/-3.7 years, there were 9
      cardiac events (5 heart failure deaths, 2 sudden deaths, and 2 re
      hospitalizations for heart failure). Only in the patients without cardiac events
      was there a significant decrease in left ventricular size (end-diastolic
      dimension decreased from 58+/-6 mm to 50+/-8 mm, p<0.001) and an improvement in
      systolic function (fractional shortening increased from 17+/-5% to 26+/-11%,
      p=0.007). However, left atrial dilation was observed in the patients with an
      event (from 39+/-5 mm to 43+/-5 mm, p=0.02). Based on proportional hazard
      analysis, left ventricular end-diastolic pressure and mean pulmonary artery
      pressure at diagnosis and left atrial dimension at the time of follow-up were
      significant predictors of poor outcome. A subset of patients with MDCM has
      impaired hemodynamics at diagnosis, left atrial dilation at follow-up and a poor
      prognosis, and must be followed carefully even if the left ventricular dilatation
      is mild.

PMID- 12074273
TI  - Novel point mutation in the cardiac transcription factor CSX/NKX2.5 associated
      with congenital heart disease.
AB  - The homeobox transcription factor CSX/NKX2.5, which is a vertebrate homologue of
      the Drosophila gene tinman, is essential for cardiac development. It is expressed
      in the early cardiac mesoderm and in heart muscle lineage throughout life.
      Homozygous deletion of CSX/NKX2.5 causes early embryonic lethality in mice
      because cardiac development is arrested at the linear heart tube stage.
      Heterozygous mutation of human CSX/NKX2.5 has been associated with various
      congenital heart diseases such as atrial septal defect (ASD), ventricular septal
      defect, tetralogy of Fallot, and tricuspid valve abnormalities, including
      Ebstein's anomaly. Additionally, CSX/NKX2.5 mutation causes atrioventricular (AV)
      conduction block with or without associated congenital heart diseases. Ten
      different heterozygous mutations have been already reported and a new point
      mutation, which is a C-to-A transition (Cys264ter) at nucleotide 901 of
      CSX/NKX2.5, results in the production of a truncated protein occurring COOH
      terminal to the homeodomain of CSX/NKX2.5. The mutation was found in a patient
      with familial ASD and first-degree AV block; 4 members from 3 generations had
      secundum-type ASD and first-degree AV block.

PMID- 12074274
TI  - Follow-up study of aortic-valve replacement surgery in patients with Takayasu's
      disease complicated by aortic regurgitation.
AB  - Aortic regurgitation (AR) is not a rare complication of Takayasu's disease and is
      now considered as an important risk factor related to mortality. Aortic-valve
      replacement surgery is the only curative treatment, but cardiac function and
      mortality after surgery have not been reported, so a follow-up study in 10
      patients with Takayasu's disease complicated by AR was performed. Six patients
      underwent aortic-valve replacement surgery and all had improvement of the
      ejection fraction and a decrease in the size of the left ventricle size on
      echocardiography. Three of the 6 cases had a remote cardiovascular event.
      Detailed pathological examination carried out in one case of the aortic valve and
      aortic specimen from surgery showed only lymphoid cell infiltration around the
      capillary in the ascending aorta, and no other inflammatory change. Inflammation
      was well controlled at surgery by pre-operative steroid therapy, so early and
      aggressive aortic-valve replacement surgery with peri-operative immunosuppressive
      therapy should be considered for patients with Takayasu's disease.

PMID- 12074275
TI  - Electrocardiographic score as a predictor of mortality after subarachnoid
      hemorrhage.
AB  - Electrocardiographic (ECG) changes are often associated with subarachnoid
      hemorrhage (SAH), but it is not well known whether these have prognostic value.
      The present study retrospectively investigated 122 consecutive patients with SAH
      caused by ruptured aneurysms. The patients were classified based on the in
      hospital outcome into 80 survivors and 42 nonsurvivors. In nonsurvivors,
      abnormalities often observed on the 12-lead ECG on arrival at hospital were
      abnormal Q wave, ST depression, and T wave inversion. The ECG score was defined
      as the total number of leads that had any of these 3 ECG abnormalities.
      Univariate analysis revealed a strong correlation of in-hospital death with the
      ECG score, the neurological status estimated by the grading of Hunt and Kosnik,
      age, and QTc interval. In age- and sex-adjusted multiple logistic regression
      analysis, the ECG score was the most powerful risk stratifier (ECG score > or = 6
      vs ECG score < 6; p=0.0026, odds ratio 14.39, 95% confidence interval 2.54
      81.71). The ECG score, a new and simple method of semi-quantification, was a
      powerful risk predictor in the present patients with SAH.

PMID- 12074276
TI  - Serum uric acid level increases in proportion to the severity of pulmonary
      thromboembolism.
AB  - Serum uric acid (UA) has been proposed as a marker for impaired oxidative
      metabolism and the present study investigated whether serum UA level increases in
      proportion to the severity of pulmonary thromboembolism (PTE) in 193 patients.
      Serum UA was repeatedly measured after treatment of PTE in 76 patients. Right
      heart catheterization was performed in a subgroup of patients (n=104). Serum UA
      on admission was significantly elevated in patients with acute PTE (6.2+/-2.3
      mg/dl) and those with chronic PTE (7.0+/-2.1 mg/dl) compared with age-matched
      controls (4.5+/-0.9 mg/ml). In particular, serum UA was markedly higher in the 27
      patients who died during hospitalization than in the remaining survivors (8.3+/
      2.2 vs 6.5+/-2.2 mg/dl, p<0.001). In acute PTE, serum UA negatively correlated
      with cardiac output, but not significantly with mean pulmonary arterial pressure.
      In chronic PTE, serum UA negatively correlated with cardiac output and positively
      correlated with mean pulmonary arterial pressure. Serum UA significantly
      decreased from 6.7+/-2.0 to 5.8+/-1.9 mg/dl with treatment, associated with an
      increase in cardiac output and in PaO2. Serum UA increases in proportion to the
      severity of PTE, and thereby may serve as a potential indicator of the efficacy
      of treatment of PTE.

PMID- 12074277
TI  - An early and complete reperfusion strategy for acute myocardial infarction using
      fibrinolysis and subsequent transluminal therapy--The FAST trial.
AB  - The efficacy and safety of fibrinolysis and subsequent transluminal (FAST)
      therapy were evaluated in 195 patients with acute myocardial infarction (AMI) for
      the early achievement of thrombolysis-in-myocardial-infarction grade 3 (TIMI-3)
      flow in the infarct-related artery. Intravenous thrombolysis using the optimal
      dose of a thrombolytic agent was initiated immediately after arrival in the
      emergency room, followed by coronary angiography and adjuvant percutaneous
      coronary intervention. A comparison of the thrombolysis alone (n=83) and
      thrombolysis plus intervention (n=112) groups showed significant differences in
      the time interval from hospital arrival to achievement of TIMI-3 flow (66.2+/
      23.7 vs 111.6+/-29.6 min, p<0.0001), creatine kinase-MB release (295+/-201 vs
      468+/-322 U/L, p=0.0003) and peak troponin T (23.6+/-16.9 vs 38.9+/-25.9 ng/ml,
      p<0.0001). No significant differences were observed in either 30-day mortality or
      complications. The TIMI-3 flow at the initial angiography was significantly
      higher with a single bolus of mutant tissue-type plasminogen activator (t-PA)
      monteplase than with an accelerated infusion of t-PA (60% vs 32%, p=0.005). In
      conclusion, the early restoration of TIMI-3 flow by FAST therapy reduced the
      degree of myocardial damage with a low risk of complications. TIMI-3 flow was
      achieved at an earlier stage with monteplase and this agent may be beneficial in
      the FAST therapy.

PMID- 12074278
TI  - Impaired exercise-induced vasodilatation in chronic atrial fibrillation--role of
      endothelium-derived nitric oxide.
AB  - Exercise capacity is often reduced in patients with atrial fibrillation (AF), but
      very few studies have focused on changes in endothelial function as a potential
      mechanism for the exercise limitation. The present study used using venous
      occlusion plethysmography to investigate whether nitric oxide (NO)-mediated
      vasodilatation is attenuated during exercise in patients with AF by measuring
      forearm blood flow (FBF) in 10 patients at rest and immediately after 2 levels of
      rhythmic handgrip exercise, before and after inhibition of NO synthesis with N(G)
      monomethyl-L-arginine (L-NMMA, 100 micromol). The measurements were repeated 1
      day after restoration of sinus rhythm by cardioversion. FBF responses to graded
      doses of acetylcholine (ACh) were also observed before and after cardioversion.
      Heart rate decreased after cardioversion, but blood pressure did not change. FBF
      at rest was not affected by cardioversion, but at the highest level of exercise
      it increased from 28.4+/-2.3 ml x min(-1) x dl(-1) before to 39.4+/-3.2 ml x min(
      1) x dl(-1) after cardioversion (p<0.05). L-NMMA significantly decreased FBF at
      rest (p<0.01) and depressed the increase in FBF response to exercise after
      (p<0.01), but not before cardioversion. The FBF response to ACh was also
      accelerated significantly after cardioversion. The present results provide new
      evidence that NO bioavailability is depressed at rest and during exercise in
      patients with AF.

PMID- 12074279
TI  - Balloon coronary angioplasty and long-term survival of non-diabetic patients with
      isolated severe left anterior descending coronary artery disease.
AB  - Although long-term survival of diabetic patients with multivessel coronary
      disease has been reported to be better in those treated with bypass surgery than
      with coronary angioplasty, it is unclear if diabetic patients who undergo
      coronary angioplasty show better long-term survival than those treated medically.
      Between 1985 and 1994, 667 consecutive patients with isolated severe (> or = 90%
      diameter stenosis) proximal left anterior descending (LAD) coronary artery
      disease were divided into 4 groups according to the initial therapeutic choice
      and their diabetic status: of 225 diabetic patients, 104 were treated medically
      and 121 underwent coronary angioplasty; of 442 non-diabetic patients, 215 were
      treated medically and 227 underwent coronary angioplasty. The primary end-point
      of follow-up was death from any cause, and the secondary end-point was cardiac
      death. Cox's proportional hazard model was used to assess the relative risk of
      baseline variables. The mean follow-up interval was 6.5+/-3.0 years. The relative
      distribution of baseline parameters of medically treated patients to those
      treated with coronary angioplasty was identical in diabetic and non-diabetic
      patients. Although non-diabetic patients who underwent coronary angioplasty
      showed better long-term survival than those treated medically, this survival
      advantage was not observed in diabetic patients. After adjustment of parameters
      using Cox's proportional hazard model, age over 65 years, coronary angioplasty
      and low left ventricular ejection fraction were independent determinants of total
      death. Long-term survival in non-diabetic patients with severe LAD coronary
      artery disease is more favorable in patients treated with coronary angioplasty
      than those treated medically, but this advantage is overridden when the patients
      are diabetic.

PMID- 12074280
TI  - Coronary revascularization improves long-term prognosis in diabetic and
      nondiabetic end-stage renal disease.
AB  - To test the hypothesis that coronary revascularization improves long-term
      prognosis in patients with hemodialysis, 80 of 121 patients (66%) on maintenance
      hemodialysis who had undergone initial coronary angiography had bypass surgery,
      catheter angioplasty, or both between 1983 and 1999. Multivessel disease was more
      frequent (p=0.01) and the duration of hemodialysis therapy was shorter (p=0.01)
      in patients with diabetes (n=61), than in nondiabetic patients (n=60). Of the
      patients who underwent revascularization, complete revascularization was achieved
      in 75% of those with diabetic nephropathy (30/40) and 83% in a similar number of
      nondiabetic patients (33/40). The 5-year survival rate from initiation of
      hemodialysis was 79% in diabetic and 96% in non-diabetic patients (p<0.01),
      exceeding published Japanese (53% vs 70%) and US (26% vs 60%) survival rates.
      When survival was studied from the date of revascularization, predictors of
      outcome were age and achievement of complete revascularization. Surprisingly,
      diabetes was not a predictor of survival outcome. Complete revascularization
      improves long-term survival in both diabetic and nondiabetic patients.

PMID- 12074281
TI  - Effect of low-dose amiodarone on atrial fibrillation or flutter in Japanese
      patients with heart failure.
AB  - The efficacy and safety of amiodarone in the management of atrial fibrillation
      (AF) or flutter in 108 Japanese patients with heart failure was retrospectively
      examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1
      month of amiodarone administration had their first recurrence, 70% of cases
      occurring within 1 year of initiation. The cumulative rates of maintenance of
      sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively.
      Amiodarone was more effective in maintaining sinus rhythm in patients with
      paroxysmal AF or flutter than in those with the persistent form (p<0.05). The
      cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and
      0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean
      heart rate during Holter monitoring was significantly decreased with amiodarone
      therapy in cases of permanent AF. Adverse effects requiring the discontinuation
      of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy
      may prevent AF or flutter in Japanese patients with heart failure.

PMID- 12074283
TI  - Constrictive pericarditis caused by calcification and organized hematoma 30 years
      after cardiac surgery.
AB  - A 54-year-old man, who had undergone atrial septal defect (ASD) closure 30 years
      previously, was admitted for exertional dyspnea and chest oppression. He
      presented with right pleural effusion and hepatomegaly. Hemodynamic
      characteristics were consistent with constrictive pericarditis caused by multiple
      cystic lesions anterior to the main pulmonary artery and right ventricle, and
      severe calcification over the posterior and diaphragmatic sides of the heart.
      Magnetic resonance imaging was useful for differential diagnosis of the cystic
      mass and at surgery, it was revealed that the cystic lesions were old hematoma
      without cells. Pericardiectomy and removal of the calcification were performed
      safely using an ultrasonic scalpel, without cardiopulmonary bypass, resulting in
      hemodynamic improvement and relief of his symptoms.

PMID- 12074282
TI  - Right ventricular ejection function assessed by cineangiography--Importance of
      bellows action.
AB  - The right ventricular ejection fraction (RVEF) can be shown theoretically as a
      mathematical function of the percent shortening in the 3 axial dimensions of the
      right ventricular cavity (the septum-free wall dimension (SF), the anterior
      posterior dimension (AP), and the tricuspid valve-apex dimension (TA) or the long
      axis dimension (LA)). There is a need to decide which mechanism is the most
      important for the RVEF in cases with neither obvious regional wall motion
      abnormalities of the left ventricle nor right ventricular overload. Forty-four
      consecutive subjects (34 males/10 females) were enrolled: 16 had normal
      hemodynamic parameters without significant coronary artery stenosis, 15 had
      hypertrophic cardiomyopathy and 13 had dilated cardiomyopathy. Biplane right
      ventricular cineangiography was performed and the percent shortening of the SF,
      AP, and TA or LA were measured. The percent shortening in the SF (34.8+/-14.7%)
      was larger than that of the AP, TA, and LA (23.2+/-8.5, 21.0+/-8.3 and 18.3+/
      7.0, respectively; all p<0.001). There was a linear correlation between the
      percent shortening of each dimension and the RVEF. The 95% confidence interval of
      the regression equation from the percent shortening of the SF and RVEF was
      located above those from the other percent shortenings, except for a lower RVEF.
      These results indicate that systolic shortening of the SF (ie, bellows action)
      plays an important role in the RVEF except for a lower ejection fraction.

PMID- 12074284
TI  - Strongyloides stercoralis infection with bloody pericardial effusion in a non
      immunosuppressed patient.
AB  - A 63-year-old Taiwan aboriginal male was admitted with exertional dyspnea,
      appetite loss and general fatigue. Echocardiography revealed moderate pericardial
      effusion and histological examination of the pericardiocentesis sample revealed
      an eosinophil-dominated bloody exudate. The larvae of Strongyloides stercoralis
      were detected in the pericardial specimen. After treatment with anti-nematodal
      agents, the eosinophilia decreased from 26% to 1% and the patient's symptoms
      improved. This is a rare case of Strongyloides-induced bloody pericardial
      effusion in a non-immunosuppressed patient.

PMID- 12074286
TI  - Two-layered appearance of noncompaction of the ventricular myocardium on magnetic
      resonance imaging.
AB  - A 60-year-old man with isolated noncompaction of the ventricular myocardium was
      evaluated by magnetic resonance imaging (MRI), which clearly showed excessively
      prominent trabeculations and deep intertrabecular recesses that correlated well
      with the findings on echocardiography and contrast enhanced computed tomography.
      On the T2-weighted and contrast enhanced MRI scans, the noncompacted myocardium
      was separated into 2 layers: a subendocardial and an endocardial layer. A
      difference in signal intensity may reflect myocardial damage that leads to
      ventricular dysfunction or arrhythmia.

PMID- 12074285
TI  - A survival case of acute mitral regurgitation and cardiogenic shock caused by
      subtotal occlusion of the first diagonal branch.
AB  - An 80-year-old woman was admitted with cardiogenic shock; she arrived in a deep
      coma with systolic blood pressure of 44 mmHg. An electrocardiogram showed ST
      elevation in I, aVL, V5 and V6, suggesting myocardial infarction in the lateral
      area of the left ventricle. A chest roentgenogram showed right pulmonary edema
      without cardiomegaly. Transthoracic and transesophageal echocardiograms revealed
      severe mitral regurgitation and a flailing anterior mitral valve leaflet,
      suggesting a ruptured papillary muscle. The patient was initially treated with
      high-dose dopamine, dobutamine and norepinephrine. Intraaortic balloon pumping
      was initiated after the patient's condition stabilized. She underwent emergency
      mitral valve replacement with a prosthetic valve. Complete rupture of the
      anterior papillary muscle was confirmed. Histological examination revealed
      necrosis of the anterior papillary muscle with inflammatory changes. She
      recovered uneventfully. Postoperative coronary angiography demonstrated subtotal
      occlusion of the first diagonal branch, and left ventriculography demonstrated
      akinesis of the lateral segment. This was a rare case in which subtotal occlusion
      of the first diagonal branch caused rupture of an anterior papillary muscle
      leading to severe mitral regurgitation.

PMID- 12074287
TI  - What is your diagnosis? A fracture of the second metacarpophalangeal sesamoid
      bone of the left forelimb.

PMID- 12074288
TI  - Canine neoplasia in the UK: estimates of incidence rates from a population of
      insured dogs.
AB  - Neoplasia is common in pet dogs but accurate figures for the incidence of tumours
      in this, as in other species, are sparse. The purpose of this study was to
      document the occurrence of tumours in a defined population of dogs. From a
      database of 130,684 insured dogs, claims relating to the investigation or
      treatment of tumours or tumour-like lesions during a 12-month period were
      accessed and followed up. A total of 2,546 claims were tumour related and were
      classified according to tumour site and type. Because the demographics of the
      insured population were skewed towards younger animals, a standard population, as
      described in the veterinary literature, was used in the calculation of tumour
      incidence rates. The skin and soft tissues were the most common sites for tumour
      development, with a standardised incidence rate of 1,437 per 100,000 dogs per
      year, followed by alimentary (210), mammary (205), urogenital (139), lymphoid
      (134), endocrine (113) and oropharyngeal (112). Canine cutaneous histiocytoma was
      the most common single tumour type, with a standardised incidence rate of 337 per
      100,000 dogs per year, followed by lipoma (318), adenoma (175), soft tissue
      sarcoma (142), mast cell tumour (129) and lymphosarcoma (114). These data are
      unique and provide a valuable basis for future research into the aetiology and
      epidemiology of canine tumours.

PMID- 12074289
TI  - Pathogenesis and outcome of extrahepatic biliary obstruction in cats.
AB  - Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in
      22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in
      six cats and one cat had an undiagnosed mass in the common bile duct. The
      remaining 15 cats had at least one of a complex of inflammatory diseases
      including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The
      most common clinical signs were jaundice, anorexia, lethargy, weight loss and
      vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common
      bile duct and gall bladder was the most commonly observed finding on abdominal
      ultrasound. Nineteen cats underwent exploratory laparotomy for biliary
      decompression and diversion. Mortality in cats with underlying neoplasia was 100
      per cent and, in those with non-neoplastic lesions, was 40 per cent. Long-term
      complications, in those that survived, included recurrence of cholangiohepatitis,
      chronic weight loss and recurrence of obstruction. Based on these findings, the
      prognosis for EHBO in cats must be considered guarded.

PMID- 12074290
TI  - A tension band technique for stabilisation of sacroiliac separations in cats.
AB  - A tension band technique was used in conjunction with a transarticular pin to
      stabilise 24 sacroiliac separations in 19 cats. The authors suggest that this
      technique is simpler and safer than the transarticular screw technique, and as
      effective.

PMID- 12074291
TI  - High rise syndrome with impalement in three cats.
AB  - Three cats were presented for management of impalement injuries sustained
      following falls from second storey windows onto spiked metal railings. Two cats
      presented with penetrating thoracic wounds and extensive pulmonary parenchymal
      trauma, while one presented with abdominal impalement and splenic rupture.
      Following stabilisation, all three cats underwent exploratory surgery. A good
      outcome was achieved in two of the cats: one with thoracic and one with abdominal
      penetration. Impalement injury secondary to free fallis a previously unreported
      variation of 'high rise syndrome' in cats.

PMID- 12074292
TI  - Diffuse bronchiolo-alveolar carcinoma in a dog.
AB  - An eight-year-old female German wirehaired pointer was presented with signs of
      respiratory distress. Clinical examination, laboratory results, thoracic
      radiography and echocardiography indicated the presence of a diffuse interstitial
      lung disease with secondary appropriate erythrocytosis, pulmonary hypertension
      and cor pulmonale. Transthoracic fine needle aspiration biopsy of the lung
      suggested malignant epithelial neoplasia. A primary lung cancer with an unusually
      diffuse distribution of miliary/micronodular lesions was found at postmortem
      examination. Histological diagnosis was bronchiolo-alveolar carcinoma. Bronchiolo
      alveolar carcinoma can occasionally occur in a diffuse fashion involving most or
      all of the lung parenchyma. In man, diffuse bronchiolo-alveolar carcinoma is
      considered a great imitator of other, more common diffuse interstitial forms of
      lung disease. This case report indicates that it is also a differential diagnosis
      to consider in dogs.

PMID- 12074293
TI  - Rhabdomyosarcoma (botryoid sarcoma) of the urinary bladder in a Maltese.
AB  - A urinary bladder tumour was diagnosed in a two-year-old female Maltese with
      haematuria and pollakiuria on the basis of ultrasonography and pneumocystography
      findings. The mass was resected, and the bladder was preserved at surgery.
      Histological and immunohistochemical examination confirmed the tumour to be a
      rhabdomyosarcoma, which has rarely been reported in small breeds of dog. There
      was no recurrence of the tumour at the original site in the urinary bladder two
      months later, when the dog died due to metastasis to the liver. This is believed
      to be the first report of bladder rhabdomyosarcoma in a Maltese.

PMID- 12074294
TI  - Cystic meningioma in a dog.
AB  - There have been few reports of the occurrence of, and treatment methods for,
      cystic meningioma in the dog. This report describes a case in a Maltese which
      presented with a three-month history of seizures. Cystic meningioma was diagnosed
      by magnetic resonance imaging using contrast medium (gadoteridol) enhanced
      images. Attempted surgical removal of the mass was successful, and the outcome
      following surgery was good.

PMID- 12074295
TI  - Compassionate cancer care.

PMID- 12074296
TI  - BSAVA awards, 2002.

PMID- 12074297
TI  - Editing a BSAVA manual: a practitioner's perspective.

PMID- 12074298
TI  - Exotic animal diseases bulletin.

PMID- 12074299
TI  - The Kendall Oration 2001. Adapting to change--challenges facing veterinary
      education.

PMID- 12074300
TI  - Successful treatments of native fauna.

PMID- 12074301
TI  - Criticisms of veterinary homeopathic practice and research.

PMID- 12074302
TI  - Recent ruling of the Federal Court about off-label use of veterinary products.

PMID- 12074303
TI  - Difficulties in training human chiropractors and physiotherapists to practice
      safely on animals.

PMID- 12074304
TI  - Exophthalmos due to a wooden foreign body in a dog.
AB  - An 8-year-old Golden Retriever dog was presented with a 10-month history of right
      sided exophthalmos. Radiographs and CT demonstrated a linear density, suggestive
      of a foreign body, in the region of the ramus of the right mandible. A 7 cm
      stick, located medial to the right zygomatic arch, was removed during exploratory
      surgery. The dog recovered with the aid of antibiotics, however was left with a
      residual facial nerve paralysis.

PMID- 12074305
TI  - Use of mandibular symphysiotomy to allow extensive caudal hemimaxillectomy in a
      dog.
AB  - A 5-year-old dog was presented with a large caudal maxillary osteosarcoma, which
      was causing extreme pain on opening of the mouth. The mass was not resectable
      through a standard oral approach. This article describes the successful use of
      mandibular symphysiotomy to allow extensive caudal hemimaxillectomy to remove the
      mass and provide excellent postoperative quality of life for the dog.

PMID- 12074307
TI  - Malignant oedema associated with blood-sampling in sheep.
AB  - Malignant oedema is a fatal disease of several animal species, produced by one or
      more members of the Clostridium genus. We report here a case of malignant oedema
      in a 1-year-old Friesian sheep after a blood sample was collected from the
      jugular vein. Clostridium septicum and Clostridium sordellii were isolated from
      the lesions and also demonstrated by a fluorescent antibody test. This report
      stresses the need for maintaining a clean environment for animals and for strict
      hygienic measures during procedures that generate wounds, together with immunity
      acquired by proper vaccination, for prevention of malignant oedema.

PMID- 12074306
TI  - Atypical multiple, papilliform, xanthomatous, cutaneous neoplasia in a goose
      (Anser anser).
AB  - An 18-month-old, male greylag goose was presented for assessment of multiple,
      semi-pedunculated cutaneous masses limited to non-feathered areas of skin.
      Initial biopsy and histopathology revealed a mesenchymal neoplasm suggestive of
      lipoblastomatosis or atypical xanthoma. Immunohistochemistry was unsuccessful in
      determining the tissue type of origin. Surgical resection of all masses was
      prevented by the mucocutaneous location of several masses. Chemotherapy using
      intralesion cisplatin was unsuccessful in resolving the masses but was well
      tolerated by the goose. Serum lipid and lipoprotein analysis revealed a
      persistent hypercholesterolaemia and hypertriglyceridaemia without biochemical
      evidence of an underlying metabolic disease. The persistent hyperlipidaemia may
      have contributed to the formation of the masses identified in this case.

PMID- 12074308
TI  - Suspected cyanide poisoning in cows fed vetch (Vicia sativa) hay.

PMID- 12074309
TI  - Screening for genetic diseases in cattle.

PMID- 12074311
TI  - Neuronal ceroid lipofuscinosis in Merino sheep.
AB  - OBJECTIVE: To characterise neuronal ceroid lipofuscinosis (NCL) in Merino sheep.
      DESIGN: A prospective clinical, pathological, biochemical and genetic study.
      PROCEDURE: NCL cases were studied from a medium-wool Merino flock, the stud of
      origin of its replacement rams, and an experimental flock established at the
      University of Sydney. RESULTS: Behavioural changes and visual impairment were
      first detected at 7 to 12 months of age and progressed, with associated motor
      disturbances and at later stages seizures, to premature death by 27 months of
      age. At necropsy there was severe cerebrocortical atrophy associated with
      neuronal loss, astrocytosis and the presence in neurons of eosinophilic
      intracytoplasmic storage bodies with the characteristics of a lipopigment. In the
      retina there was progressive loss of photoreceptor cells. Storage bodies isolated
      from fresh brain, liver and pancreas formed electron-dense aggregates and coarse
      multilamellar and fine fingerprint profiles ultrastructurally, and consisted
      mainly of the hydrophobic protein, subunit c of mitochondrial ATP synthase. A
      homozygosity mapping approach localised the gene causing the disease in Merino
      sheep to the chromosomal region (OAR7q13-15) associated with NCL in South
      Hampshire sheep. CONCLUSION: NCL in Merino sheep is a subunit c-storing disease,
      clinically and pathologically similar to NCL in South Hampshire sheep. We propose
      that the disease in both breeds represents mutation at the same gene locus in
      chromosomal region OAR7q13-15.

PMID- 12074310
TI  - Genotyping Brahman cattle for generalised glycogenosis.
AB  - OBJECTIVE: To develop procedures for genotyping Brahman cattle for loss-of
      function alleles within the acidic alpha-glucosidase gene and to assess the risk
      of generalised glycogenosis in Australian Brahman cattle. DESIGN: PCR assays for
      three loss-of-function alleles were designed to exploit internal restriction
      sites within acidic alpha-glucosidase amplicons that are independent of allelic
      variants at the mutant sites. RESULTS: Genotyping 8529 clinically normal Brahmans
      between August 1996 and August 2001 revealed 16.4% were heterozygous for the more
      common of the two mutations (1057deltaTA, often referred to as the 'E7' mutation)
      that cause generalised glycogenosis in this breed. The less common 1783T mutation
      (often referred to as the 'E13' mutation) was restricted to descendants of one
      imported bull, and was not detected in 600 randomly selected Brahmans. Prior to
      definition of these two disease-causing mutations, 640 (18%), and 14 (0.4%), of
      3559 clinically normal Brahmans analysed between January 1994 and December 1996,
      were heterozygous, and homozygous, respectively, for a silent polymorphism (2223G
      ->A) that is associated with generalised glycogenosis. In addition to the
      1057deltaTA and 1783T mutations, approximately 15% of Brahmans were found to be
      heterozygous for a single base substitution in exon 9 (1351T, commonly referred
      to as the 'E9' mutation) that significantly reduces acidic alpha-glucosidase
      activity, but has not been associated with clinical disease. These three loss-of
      function alleles were found in Brahmans imported, or selected for import, from
      the USA. CONCLUSION: The PCR procedures reported here represent a significant
      improvement in reliability and accuracy over previous published methods.
      Utilisation of these PCR/restriction enzyme based assays will facilitate precise
      selection against the 1057deltaTA and 1783T alleles, and consequently reduce the
      incidence of generalised glycogenosis in registered and commercial Brahman herds.

PMID- 12074312
TI  - Persistence of rabbit haemorrhagic disease virus in decomposing rabbit carcases.

PMID- 12074313
TI  - Variations in residues of persistent organic pollutants in a platypus
      (Ornythorhynchus anatinus) at consecutive samplings.

PMID- 12074314
TI  - Abdominal malignant mesothelioma in a mouse.

PMID- 12074315
TI  - Resistance to macrocyclic lactones in nematodes of goats.

PMID- 12074316
TI  - Feral pigs--the time bomb.

PMID- 12074317
TI  - Feral pigs--the time bomb.

PMID- 12074318
TI  - Reducing the risk of colorectal cancer by intervening in the process of
      carcinogenesis: a status report.
AB  - Risk factors for colorectal cancer have been identified, and significant advances
      have been made in understanding the process of colorectal carcinogenesis. The
      transition from normal colonic mucosa to adenomatous polyp to adenocarcinoma is a
      gradual process involving genetic and epigenetic instability that can take
      decades, offering numerous opportunities for early detection (e.g., colonoscopy
      screenings), lifestyle changes (e.g., reduced red meat intake, increased physical
      activity, and reduced alcohol/ tobacco exposure), and chemopreventive
      interventions. Aspirin and various other nonsteroidal anti-inflammatory drugs may
      have chemopreventive benefits for colorectal cancer and other human epithelial
      carcinomas, butthe long-term use of nonsteroidal anti-inflammatory drugs is
      associated with serious gastrointestinal side effects. Recently, overexpression
      of cyclooxygenase-2 has been documented in colorectal tumors and numerous other
      pre-cancers and cancers. The development of selective cyclooxygenase-2
      inhibitors, such as celecoxib, provides an opportunity for preventive
      intervention in the carcinogenic process. Celecoxib has been approved for the
      management of familial adenomatous polyposis and is under investigation for the
      management of sporadic colorectal polyps and for its potential as a
      chemopreventive agent for other cancers.

PMID- 12074319
TI  - The Ki-67 index and survival in non-small cell lung cancer: a review and
      relevance to positron emission tomography.
AB  - PURPOSE: We reviewed the current literature to discover the range of studies
      covering tissue-based and noninvasive methods for determining tumor stage and the
      prognostic value of staging in non-small cell lung cancer. DESIGN: Despite
      refinements in staging of non-small cell lung cancer, each stage remains
      heterogeneous because each stage contains patients who are at higher risk for
      recurrence than other patients within the same stage. Tissue-based and
      noninvasive methods have been investigated to complement tumor stage in assessing
      non-small cell lung cancer prognosis. The prognostic significance of tumor
      proliferation assessed by Ki-67 protein expression has been demonstrated in non
      small cell lung cancer. RESULT: Recent positron emission tomography studies have
      also shown both prognostic value in non-small cell lung cancer uptake of [F-18]
      fluorodeoxyglucose (FDG) and correlation between non-small cell lung cancer FDG
      uptake and tumor proliferation. DISCUSSION: We reviewed the prognostic
      significance of Ki-67 expression in non-small cell lung cancer and related it to
      positron emission tomography.

PMID- 12074320
TI  - Salvage radiotherapy for elevated PSA levels following prostatectomy.

PMID- 12074321
TI  - Low level laser therapy: a real hope in the management of chemo-induced and
      radiation-induced mucositis?

PMID- 12074322
TI  - Evolving considerations in the design and interpretation of phase I trials
      investigating gemcitabine based chemoradiotherapy regimens.

PMID- 12074323
TI  - Postprostatectomy salvage radiation therapy for prostate cancer: impact of
      pathological and biochemical variables and prostate fossa biopsy.
AB  - PURPOSE: A subgroup of prostate cancer patients who have experienced biochemical
      relapse after radical retropubic prostatectomy (RRP) can benefit from radiation
      therapy to the prostate fossa. These patients demonstrate biochemical relapse
      secondary to local failure in the absence of distant failure. In order to define
      this subgroup, we investigated the impact of pathological and biochemical
      variables and pre-radiation therapy biopsy of the prostate fossa on biochemical
      disease-free survival (bNED) and initial prostate-specific antigen response.
      METHODS: Sixty-two patients with localized prostate cancer who had biochemical
      relapse after RRP were treated with post-RRP radiation therapy localized to the
      prostate fossa (median dose, 6120 cGy) and were subsequently followed up for a
      median time of 47 months. Cox regression analyses and Kaplan-Meier estimates for
      bNED were used to identify prognostic variables. The Fisher's exact test was used
      to test the interaction of initial prostate-specific antigen response with
      identified prognostic variables. RESULTS: Cox regression analysis of bNED as a
      function of pathological and biochemical parameters showed that only Gleason's
      score was a significant predictor of bNED. On univariate analysis, seminal
      vesicle involvement was also found to be a significant predictor. Prostate fossa
      biopsy result was not significantly related to bNED. Because of the overall high
      rates of biochemical failure, we wished to identify a high-risk subgroup that did
      not have local relapse as a component of biochemical relapse after RRP. We
      assessed initial biochemical response following radiation therapy as a surrogate
      for local relapse. A complete biochemical response was observed in 50% of
      patients, and a partial biochemical response was observed in an additional 34%,
      yielding an overall biochemical response rate of 84%. When stratified by
      Gleason's score, seminal vesicle, pre-radiation therapy prostate-specific
      antigen, and biopsy result, response rates greater than 50% were seen for all
      subgroups. CONCLUSIONS: Gleason's score and seminal vesicle involvement predicted
      bNED after post-RRP radiation therapy in our cohort. Overall biochemical response
      rates were high in all subgroups, suggesting that all subgroups demonstrated a
      high likelihood of residual local disease as a component of failure. Pre
      radiation therapy biopsy was predictive of neither bNED nor overall biochemical
      response.

PMID- 12074324
TI  - Pilot study of laser effects on oral mucositis in patients receiving
      chemotherapy.
AB  - PURPOSE: The purpose of this study was to examine the effectiveness of laser
      therapy in the prevention and/or healing of chemotherapy-induced oral mucositis
      lesions. This study also evaluated the ease and feasibility of the laser therapy
      and the impact of the treatment on improving the patient's quality of life.
      PATIENTS AND METHODS: Fifteen patients with an episode of prior chemotherapy
      induced grade 3 or 4 mucositis with 5-fluorouracil continuous infusion consented
      to participate in this study. All patients were provided with standardized mouth
      care instructions at the initiation of chemotherapy treatments. Enrolled patients
      received laser therapy treatments 24 hours before the chemotherapy and then
      recommenced weekly with evenly distributed exposure to the standardized
      designated areas by one operator during the entire cycle of chemotherapy at the
      same doses until the mucositis resolved or the chemotherapy cycle was completed.
      lntraoral perfusion was measured by laser Doppler technology. Patients were
      assessed for response to laser therapy according to standardized mucositis
      grading criteria by evaluating development of lesions, extent and duration of
      lesions, and time to healing. The effect of laser therapy on ability to continue
      planned chemotherapy, the reduction in dose, delays, and ability to maintain
      planned dose intensity were assessed. The impact of laser therapy on pain control
      was evaluated using the visual analogue score. A quality-of-life survey was
      completed by each patient at the initiation of chemotherapy and then weekly
      throughout the chemotherapy. RESULTS: Eleven of 15 patients experienced grade 0
      mucositis, three patients experienced grade 1 to 2 mucositis, and one patient
      experienced grade 3 to 4 mucositis. Fourteen patients completed the lasertherapy
      as planned, and none of the patients withdrew from the laser therapy treatments
      because of noncompliance. One patient continued to experience grade 4 mucositis
      that necessitated an interruption in the planned chemotherapy regimen and,
      consequently, the laser treatment. Patients tolerated the laser therapy very well
      and did not report any increased discomfort. No significant changes in perfusion
      were observed as a result of laser therapy. DISCUSSION: In this pilot study,
      laser therapy significantly reduced the incidence and the severity of mucositis
      in chemotherapy patients. The laser therapy does not appear to promote wound
      healing by affecting the intraoral perfusion, as assessed by Doppler
      measurements. The mechanisms involved in the mediating of the observed effects
      remain unknown at this time. Continued research is warranted to determine the
      optimal laser wavelength and parameters.

PMID- 12074325
TI  - Concurrent infusional gemcitabine and radiation in the treatment of advanced
      unresectable GI malignancy: a phase I study.
AB  - PURPOSE: Preclinical studies have demonstrated significant synergistic tumor cell
      death when gemcitabine is combined with radiation therapy. The optimal mode for
      concomitant delivery of drug and radiation therapy remains to be determined. A
      phase I/II study was undertaken to establish the maximum tolerated dose of
      infusional gemcitabine when combined with radiation therapy in advanced
      gastrointestinal malignancies and to assess the response to treatment. MATERIALS
      AND METHODS: Twenty-five patients with advanced or recurrent gastrointestinal
      malignancy were entered in this dose-escalation study. The initial dose of
      gemcitabine was 50 mg/m2 as a 24-hour continuous intravenous infusion given
      weekly x 3 with concurrent radiation therapy. The patients were given a week off
      chemotherapy after the third injection. The radiation therapy was continued
      during that week. Gemcitabine was thereafter resumed weekly for another 3 weeks
      or until the patient completed the radiation therapy (whichever was earlier).
      Five patients were treated at each dose level. The dose of the drug was escalated
      in increments of 50 mg/m2 if the toxicity was acceptable at the previous level
      until the maximum tolerated dose was established. Thirteen patients with advanced
      unresectable colorectal cancer and 12 patients with advanced unresectable
      pancreaticobiliary cancers were enrolled on the study. Radiation was delivered at
      180 cGy/fraction to a total dose of 4000 cGy +/- boost. Because toxicity was
      severe at the 150 mg/m2 dose level, three additional patients were entered at
      this dose level. The dose was then dropped to 125 mg/m2, and five more patients
      were entered at this dose level. Two additional patients were then added in order
      to assess toxicity. Patient follow-up ranged from 4 to 22 months, and the median
      was 8 months. RESULTS: All patients were evaluable for toxicity. The doses of 50
      and 100 mg/m2 were well tolerated, but at 150 mg/m2, six of eight patients
      experienced grade 3 or greater toxicity. The dose was de-escalated to 125 mg/m2,
      and three of seven patients showed grade 3 diarrhea and weight loss. Clinical
      tumor response was evaluable in 20 patients. Ten patients had a complete clinical
      response (50%), five patients had a partial response (25%), three patients had no
      response, and two patients had progression of disease. No patients experienced
      late toxicities related to either gemcitabine administration or radiation
      therapy. Twelve patients are currently alive. CONCLUSION: Based on these results,
      it appears that the maximum tolerated dose for weekly 24-hour infusion of
      gemcitabine combined with radiation therapy is 100 mg/m2. Gemcitabine appears to
      be a potent radiation sensitizer, and when combined with radiation therapy, it
      has shown encouraging tumor responses. In this study, we found an overall
      response rate of 75% in patients with locally advanced stage of disease. Further
      evaluation of gemcitabine at 100 mg/m2 is being undertaken in preparation for a
      confirmatory multi-institutional phase II study.

PMID- 12074326
TI  - Pathological response to preoperative chemoradiation worsens with anemia in non
      small cell lung cancer patients.
AB  - PURPOSE: Positive links between hemoglobin level and therapeutic tumor response
      are well documented in carcinoma of the cervix and the head and neck, but little
      evidence of such a link exists for lung cancer. We analyzed our series of
      patients treated with preoperative chemoradiation for stage IIIA non-small cell
      lung carcinoma. PATIENTS AND METHODS: Between June 1992 and February 2000, 41
      consecutive patients with clinical stage IIIA (N2, documented by mediastinoscopy
      or another invasive procedure) non-small cell lung carcinoma received
      preoperative-intent chemoradiation. The median preoperative radiation dose was
      48.6 Gy, and all patients received cisplatin- or paclitaxel-based chemotherapy.
      Response was graded on a four point scale: (1) progressive disease before surgery
      and/or technically inoperable; (2) stable disease with resection performed, but
      specimen containing > 50% viable tumor; (3) partial response with specimen
      containing < 50% tumor; and (4) complete response or near-complete response: RO
      resection with no residual carcinoma or pT1NO with only microscopic residual
      foci. Pretreatment hemoglobin values were correlated with pathological outcome
      using ANOVA and the non-parametric test for trend across ordered groups. RESULTS:
      The mean hemoglobin level for groups 1 through 4 was 11.8, 12.1, 12.5, and 13.2
      respectively, and the association was statistically significant. If the analysis
      was limited to patients actually undergoing surgery (eliminating group 1), the
      association remained significant. The nonparametric test for trend across ordered
      groups was also significant with and without group 1. DISCUSSION: Our analysis
      supports the hypothesis that response to chemoradiation of non-small cell lung
      carcinoma improves with increasing hemoglobin levels.

PMID- 12074327
TI  - The prognostic value of invariant chain (Ii) and Her-2/neu expression in
      curatively resected colorectal cancer.
AB  - BACKGROUND: Current methods to predict outcome for patients with curatively
      resected colorectal cancer are not ideal. The combined use of molecular markers
      and clinicopathologic features may better identify patients who are at risk for
      recurrence. The Her-2/neu and invariant chain molecules may be important in
      cancer development and progression, but their usefulness as clinical predictors
      of outcome in colorectal cancer has not been well studied. METHODS: We used
      immunohistochemistry to determine the expression of Her-2/neu, invariant chain,
      p27, and p53 in primary tumor samples from 156 patients with curatively resected
      stage I-III colorectal cancer. The association between expression and clinical
      outcomes was assessed by univariate and multivariate analysis. RESULTS: Her-2/neu
      expression was detected in only 24% of cases, and high levels of invariant chain
      were detected in only 15%. Although patients whose tumors overexpressed Her-2/neu
      survived longer than those with non-overexpressing tumors, neither Her-2/neu nor
      invariant chain were independently associated with survival. Consistent with
      previous reports, high p27 expression was associated with improved outcome,
      whereas overexpression of p53 was associated with worse outcome. CONCLUSIONS: Our
      study did not reveal a statistically significant association between Her-2/neu or
      invariant chain expression and clinical outcomes in patients with curatively
      resected colorectal cancer. However, the data suggest that Her-2/neu could be a
      favorable prognostic variable. Because of the low frequency of Her-2/neu
      expression, larger numbers of patients need to be studied for this question to be
      adequately answered.

PMID- 12074328
TI  - Mammographically detected breast cancers and the risk of axillary lymph node
      involvement: is it just the tumor size?
AB  - PURPOSE: In early breast cancer the knowledge of the risk of axillary node
      involvement is important in determining local as well as systemic therapy.
      Because of the increased acceptance of mammography, there has been an increase in
      the diagnosis of small, mammographically detected tumors. The objective of this
      study is to determine whether mammographically detected breast cancers have a
      lower risk of axillary node involvement compared to those detected clinically.
      PATIENTS AND METHODS: From our patient database of stage I and II breast cancer
      we identified 980 patients with tumors < or = 2 cm whom had axillary node
      dissection. Four hundred thirty-five (44%) patients presented with abnormal
      mammograms without clinically palpable tumors; 545 (56%) patients had clinically
      detected tumors. The median size of the mammographically detected tumors is 1.0
      cm, and the median size of the clinically detected tumors is 1.5 cm. The median
      age of the patients with mammographically detected tumors is 61 (range: 29-87)
      compared to 53 (range: 27-88) in those with palpable tumors. RESULTS: Fourteen
      percent of the patients with mammographically detected tumors had positive
      axillary nodes compared to 26% of those with clinically detected tumors. Eight
      percent of patients with mammographically detected tumors had a single positive,
      while the clinically detected tumors 11% had a single positive node. Thirteen
      percent of patients with < or = 1 cm tumors and 25% with tumors 1.1 cm to 2 cm
      had positive axillary nodes. Because the smaller size of the mammographically
      detected tumors could explain the lower proportion of positive axillary nodes, we
      analyzed separately the < or = 1 cm tumors. In the group of < or = 1 cm tumors,
      9% had positive axillary nodes iftheywere mammographically detected compared to
      19% if clinically detected. Four percent had a single positive node while 5% had
      multiple positive nodes. If the tumors were palpable and < or = 1 cm 9% had a
      single positive node and 10% had multiple positive nodes. Mammo
      graphicallydetected tumors < or = 1 cm had similargrade to clinically detected
      tumors. In multivariate analysis, method of detection remains a significant
      variable impacting on the risk of axillary node involvement even in tumors < or =
      1 cm. DISCUSSION: The risk of axillary node involvement is lower in
      mammographically detected tumors compared to clinically detected tumors
      independent of tumor size or grade. Mammography detects tumors early in their
      metastatic progression. The majority of the axillary node-positive patients who
      are mammographically detected have a single positive axillary node. Method of
      detection may need to be considered when assessing the risk of axillary node
      involvement and incorporated in the staging.

PMID- 12074330
TI  - Vascular access.

PMID- 12074331
TI  - Approach to vascular access for hemodialysis: experiences from the Republic of
      Macedonia.
AB  - Eight thousand eight hundred and forty nine different vascular hemodialysis
      accesses were performed in the period from 1976 until 1999 at the Department of
      Nephrology, Skopje: 3,114 native arterial-venous fistula (AVF), 715 arterial
      venous shunts (AVS), 4,964 temporary or permanent catheters (4,411/88.86%
      femoral, 410/8.26% subclavian, 143/2.88% jugular) and 56 PTFE vascular grafts.
      Femoral catheterization (4,312/86.86%) is the favoured solution if a temporary
      vascular dialysis access is taken into consideration. The most popular chronic
      dialysis angio-access in our country is native AVF (90.5% of 3,440 permanent
      dialytic vascular accesses). The tunneled subcutaneously positioned catheters as
      a permanent dialytic angio-access were present in 270 cases (7.9%): 99 in femoral
      veins (our original method), 123 in subclavian veins and 48 catheters in jugular
      veins. The synthetic vascular grafts-PTFE (polytetrafluoro-ethylene) represent
      only 1.6% of all dialysis angio-accesses. The number of preventive AVFs created
      in patients with preterminal end-stage renal disease eventually increased; from
      14% in the eighties, 20.8% after 10 years and 31.50% in 1999. Most of the
      preventive AVFs are done in outpatients 71.8% in 1999. This year 44.4% of all
      chronic vascular access were created in the same way. We prefer femoral catheters
      for both temporary and permanent access because our results show that femoral
      catheterization has a lower rate of early complications when compared to the
      subclavian catheterization group; the rate of late complications (thrombosis,
      stenosis, infections) is lower or the same; infections in femoral
      catheterizations are less frequent, compared to subclavian and jugular ones. Our
      contributions in the field of vascular access surgery are the three original
      methods which are constantly used at the Department: 1. Combination of temporary
      (AVS) and permanent vascular access (AVF) using the same blood vessels, performed
      in one surgical act; 2. Tunneled femoral catheter as a permanent vascular access
      for hemodialysis (2 types: on the abdominal wall and on the infrainguinal region 
      thigh); 3. Reduction of hyper-flow in AVF without the operation of "banding",
      with ligation of the artery before arteriovenous anastomosis.

PMID- 12074329
TI  - Randomized phase II trial of either fluorouracil, parenteral hydroxyurea,
      interferon-alpha-2a, and filgrastim or doxorubicin/docetaxel in patients with
      advanced gastric cancer with quality-of-life assessment: eastern cooperative
      oncology group study E6296.
AB  - PURPOSE: The Eastern Cooperative Oncology Group conducted a randomized phase II
      trial to determine the objective response rates, toxicities, and overall survival
      and to assess effects on quality of life for two combination regimens in patients
      with advanced gastric cancer. PATIENTS AND METHODS: All patients had biopsy
      proven, untreated metastatic gastric cancer with measurable disease. The FHIG arm
      employed infusional fluorouracil (F), 2.6 g/m2, given intravenously over 24 hours
      once perweek for 6 weeks; infusional hydroxyurea (H), 4.3 g/m2, given
      intravenously over 24 hours once per week for 6 weeks; and interferon-alpha-2a
      (1), 9 MU given subcutaneously three times per week, once per week for 6 weeks.
      The AD arm employed doxorubicin (A), 50 mg/m2, and docetaxel (D), 75 mg/m2, both
      given intravenously every 21 days. Quality of life was measured by the FACT
      Fatigue scale and a novel questionnaire assessing interferon-mediated fatigue.
      RESULTS: Twenty-nine patients were enrolled; 23 were eligible and evaluable.
      Twelve were enrolled on FHIG and 11 on AD. The major grade > or = 3 toxicities
      were neuromotor (46%) in patients receiving FHIG and granulocytopenia (91%) in
      those receiving AD. There were two fatalities in the AD arm. There was one
      partial responder on FHIG (8.3%) and none on AD. The median survival was 6.6
      months for FHIG and 10.1 months for AD. Quality-of-life analysis did not show
      substantial cumulative fatigue in patients treated with FHIG. CONCLUSIONS:
      Neither regimen demonstrated enough activity to serve as a platform for the
      development of further clinical regimens against gastric carcinoma. A subset of
      patients receiving interferon was able to tolerate therapy without deterioration
      in quality of life.

PMID- 12074332
TI  - Various clinical approaches to minimise complications in peritoneal dialysis.
AB  - The main reason for a failure of peritoneal dialysis is due to technical problems
      or infections. By starting PD immediately after the insertion of a dialysis
      catheter (instead of starting HD before optimal healing of the PD-catheter) it
      may be easier to achieve acceptance for PD by the patients. An easy and tight
      access is achieved when inserting the PD-catheter through the rectus muscle,
      fixing it with three purse string sutures, two of them fixing the inner cuff
      between the peritoneal membrane and the inner rectus fascia. Thereby early and
      late leakage will be rare and good drainage is normally achieved besides a low
      risk for exit site infections. Using Coloplast adhesive insulin can be injected
      into the PD bags in a simple way even by patients with bad vision. Using
      ultraviolet light, as additional exchange device (UV-box), the risk for
      peritonitis is reduced compared to classic manual connection. Using the Y-set or
      duo-bag system the risk for peritonitis is further lowered. Malfunction by
      dislocation of the intraperitoneal part of the catheters can often be corrected
      without surgery using a bent stylet. A controlled study showed that antibiotic
      prophylactics could significantly reduce the risk for peritonitis in the follow
      up after insertion of PD catheters. Additionally the risk for peritonitis is
      reduced using a special connector for the PET-sampling procedures. X-ray of
      catheter location in the abdominal cavity can be performed by injection of 20-ml
      contrast media into 100 ml of PD fluid residing in the PD-bag. After mixing,
      small portions of this fluid can be infused into the abdomen for X-ray
      determination of the location. An increased ultrafiltration failure during PD may
      be due to use of beta-blocker medication. After ceasing this medication recovery
      may occur. Avoiding pets in the room used for PD-exchange may lower the risk for
      peritonitis further. A devoted nurse and physician will keep up the patients'
      spirit and help to convert patients not suitable for PD to HD or the other way
      round. By such measures the incidence of peritonitis can be reduced to 1 in 40
      treatment months or less.

PMID- 12074333
TI  - Vitamin E as an antioxidant agent in CAPD patients.
AB  - Oxidative stress, increased lipid peroxidation and decreased activity of
      antioxidant systems may contribute to the accelerated development of
      atherosclerosis in chronic renal failure patients during renal replacement
      therapy. The aim of the study was to investigate the influence of vitamin E (400
      mg/day) on some antioxidant defense parameters in CAPD patients. In fourteen CAPD
      patients, erythrocyte antioxidant enzymes, superoxide dismutase (SOD),
      glutathione peroxidase (GPX) and catalase (CAT), the concentration of plasma
      malondialdehyde (MDA), vitamin A, vitamin C and vitamin E were investigated. The
      study was divided into two periods. Each period lasted six weeks. In the first
      period patients received orally vitamin E 400 mg/day, in the second period they
      did not receive vitamin E or other antioxidant drugs. Each parameter was
      determined at the beginning of the study and at the end of each period. Six CAPD
      patients were treated by erythropoietin (EPO) and received orally pyridoxine 20
      mg/day and the others without EPO treatment received pyridoxine 5 mg/day. Six
      week treatment by vitamin E (400 mg/day) led to the significant increase of serum
      vitamin E (from 33.6+/-9.0 to 49.3+/-15.5 micromol/L) and to the significant
      decrease of MDA (from 2.62+/-0.5 to 2.36+/-0.4 micromol/L). The mean values of
      erythrocyte enzymes were in or under the lower margin of normal range and were
      not influenced by vitamin E in CAPD patients. The results of our study showed
      that orally administered vitamin E is a very important antioxidant agent for CAPD
      patients.

PMID- 12074334
TI  - Filtration fluid for hemodialysis treatment.
AB  - Bacterial contamination of dialysis fluid has long been recognized as a problem
      in hemodialyis. Cytokines released as a consequence of contaminated dialysis
      fluid are believed to be responsible for many acute and chronic side effects in
      patients undergoing renal replacement therapy. For several years now, attempts
      have been made to eliminate pyrogenic substances and ensure a sterile and
      endotoxin-free dialysis fluid. A recent dialysis fluid filter known as DIASAFE,
      containing a membrane based on Polysulfone (Fresenius), was tested for a period
      of 1,000 hours (approx. 14 weeks). Dialysis fluid samples were collected once
      weekly before and behind the filter and cultivated for detection of
      microorganisms and endotoxins. Additionally, starting after the fourth week of
      the study, serum samples were collected weekly and the beta2-microglobulin
      concentration was determined. The filter reduced microorganisms at a rate of at
      least 10(5) and in the majority of cases (86% of samples) by more than 106. Under
      clinical conditions the stability and microbiological functionality of the
      filters could be demonstrated for more than 1,000 hours and 150 disinfecting
      cycles. In four cases of endotoxin burden (> 0.5 IU/ml) in the dialysis fluid in
      front of the filter the concentration behind the filter was lower than 0.1 IU/ml,
      indicating effective reduction of endotoxins. A tendency to a reduction of beta2
      microglobulin in serum from 32.5+/-3.9 mg/L to 21.5+/-5.3 mg/L was observed.
      These results indicate that the dialysis fluid filter used was effective,
      dramatically reducing the bacterial contaminants in dialysis fluid, thus
      protecting patients from the potentially harmful acute and long-term life
      threatening consequences of contaminated dialysis fluid.

PMID- 12074336
TI  - Extracorporeal treatment strategy in acute renal failure.
AB  - The mortality of acute renal failure remains high (around 50-70%) despite
      manifold improvements in terms of techniques and equipment for renal replacement
      therapies as well as patient monitoring and intensive care support. At present,
      it is not clear if the method chosen for renal replacement therapy, i.e.
      intermittent hemodialysis or continuous hemofiltration, might impact on the
      outcome of these patients. Whilst earlier retrospective studies suggested that
      CVVH might result in better survival and renal recovery in acute patients, recent
      prospective studies indicated that this may not be the case or, conversely,
      outcomes may be better with IHD. These studies were, however, not evenly
      randomised in terms of illness severity or were too small to produce conclusive
      results. In addition, a meta-analysis of 9 published prospective studies in 692
      pts. indicated a similar mortality with CVVH vs. IHD. Some of the studies
      enrolled for this meta-analysis, however, suffered from methodological and/or
      randomisation problems, thus this important question remains to date unanswered.
      Typically, CVVH is chosen for treating patients with hemodynamic instability and
      volume overload. In such cases, however, CVVH should be performed with a filtrate
      volume of at least 35 ml/kg body weight per hour as this was shown to be
      associated with better survival as compared to smaller filtrate volumes. A second
      controversy exists to date whether the choice of the dialyzer membrane might be
      of relevance for the outcome of patients with acute renal failure. Earlier
      studies indicated that the use of biocompatible membranes in these patients may
      result in improved patient survival and renal recovery. More recently, however,
      similar studies could not confirm these results. Another meta-analysis of
      controlled prospective trials (671 patients in 7 separate studies) calculated a
      relative mortality risk of 1.01 for cuprophan vs. biocompatible membranes. Thus,
      the choice of the dialyzer membrane should be based on individual assessment
      rather than treatment bias.

PMID- 12074335
TI  - Dialysis in adults in year 2000 in the Republic of Macedonia.
AB  - 1,019 adult patients with terminal renal failure were treated with dialysis (D)
      in the first part of the year 2000 in the Republic of Macedonia. 1,010 patients
      (99%) were treated with chronic intermittent (maintenance) hemodialysis (HD)
      while nine patients (1%) were on continuous ambulatory peritoneal dialysis
      (CAPD). For the children, a special peritoneal dialysis program was developed;
      509 patients per million of the population (PMP) were on dialysis. The Republic
      of Macedonia is, therefore, among those central and eastern European countries
      with a higher PMP number in the treatment of end-stage renal disease, following
      Croatia, the Czech Republic and Slovenia. The patients were treated at 18 Centers
      in a network of HD Centers at a distance of 30-50 km. from their place of
      residence in order to facilitate their access to treatment and to work. All
      patients who have had symptoms indicating need for treatment with D were accepted
      for treatment. The government payed all the expenses of the treatment and the
      salaries of the staff. 56% were male and 44% were female patients. The youngest
      patient was aged 9 and the oldest was 82 years old. There has been an increase in
      the age of the patients on D as well as an increase in their number. In 1993 we
      had 727 patients being treated with D, and now we have 1,019 with a constant
      increase in the number of patients with ESRD and a need for D and renal
      transplantation. Mortality per year at the different Centers ranged from 8-19% in
      1999 and the average is 12%. Glomerulonephritis (GN)--both primary and secondary-
      is the main cause of renal failure (RF) in some Centers up to 45%. Tubulo
      interstitial disease follows GN. ADPKD patients constitute 9.4% with a difference
      among the Centers of 3-29%, and diabetic nephropathy is found in 10%, 5-15% in
      different Centers. 11-61% of patients have an unknown etiology. 352 patients are
      on treatment with human recombinant erythropoietin (rhuEPO) - in some Centers up
      to 60%. The mode of application was subcutaneous and the initial dose is 20 U/kg
      body weight and the mean maintenance dose of EPO per patient weekly is 4,000 U.
      The Cimino-Brescia arteriovenous fistula is being applied as a standard vascular
      access. The survival rate of our patients treated with maintenance HD at 5 years
      was 58%. CAPD and particularly renal transplantation are to be further developed
      as alternative methods in treating terminal renal failure.

PMID- 12074337
TI  - Priorities in renal replacement programs.
AB  - The various alternative programs in renal replacement therapy have precise
      meritocratic ranking which unfortunately is still largely ideal today. New
      directions and scientific plans (bioartificial kidney, new immunomodulators, gene
      therapy) have to be followed to make today's ideal ranking become reality.

PMID- 12074338
TI  - Ischemic dilatative cardiomyopathy and aneurysms of the left ventricular cavity:
      transplantation vs alternative surgery.
AB  - Patients with terminal end-stage heart failure due to severe coronary disease
      associated with dilatative cardiomyopathy have an annual mortality of 30-50%.
      Between July 1997 and December 1999, 21 patients at the University Hospital in
      Frankfurt, and 25 patients from Skopje underwent total circular repair with
      simultaneous coronary artery bypass.

PMID- 12074339
TI  - Validation of a two-pool model for the kinetics of beta2-microglobulin.
AB  - Secondary amyloidosis due to beta-2-microglobulin (beta2-m) is a serious long
      term complication in patients on regular dialysis therapy. Beta2-m can be
      considered a middle-molecule marker used to facilitate the assessment of dialysis
      efficacy. For this purpose, a validated model that calculates characteristic
      efficacy parameters, such as Kt/V, TAC and generation rate, is needed. There is
      general agreement that beta2-m-kinetics should be described by a two-pool model,
      but little has been published to validate such an approach. We measured the beta2
      m concentration profiles of eight stable patients during hemodialysis (HD) at the
      start of treatment, after 30 minutes, after 60 minutes, and every hour until the
      end. Thereafter they were measured at 10-minute intervals for an hour. The
      dialyser clearances were determined from the plasma concentrations in front of
      and behind the dialyser twice during each session - after 1 hour, and 4 hours
      from the start of treatment. The kinetic parameters of a two-pool model (e.g. the
      compartment volumes V1 and V2, the mass transfer coefficient K12 and the
      generation rate G) were determined from the optimal fit of the measured
      concentration profile. The table below summarises the results by giving the mean
      and standard deviation for each parameter: [table: see text]. Inter-individual
      differences in V1/V2 and K12 were high, ranging from 2.5 to 10.0 for V/V2 and
      from 26 to 140 for K12. Error analysis suggested that these wide ranges were due
      to the method and that in reality the probable range of V is 25-36% of TBW, of
      V1/V2 3.5-5.3, and of K12 30-80 ml/min. With standard values for these three
      parameters (V = 30% of TBW, V/V2 = 4.4 and K12 = 55 ml/m), equal for all
      patients, and their respective ranges, Kt/W can be calculated with a standard
      deviation of 13%. Kt/W > 1.2 secures the maximum possible beta2-m removal with
      three HD treatments a week. CONCLUSIONS: The parameters of a two-pool model of
      beta2-m kinetics can be derived from concentration profiles obtained under
      routine dialysis conditions, but accuracy is not completely satisfactory. Similar
      to the dialysis dose for urea (Kt/Vurea) the dialysis dose for beta2-m (Kt/Vbeta2
      m) can be calculated from the pre- and post-dialysis concentrations of beta2-m,
      body weight, ultrafiltration and dialysis time. Kt/Vbeta2-m > 1.2 secures the
      maximum possible removal of beta2-m in HD with three sessions per week.

PMID- 12074340
TI  - Sodium and body fluid homeostasis in profiling hemodialysis treatment.
AB  - Acute adverse side-effects of hemodialysis such as hypotension, muscle cramps,
      osmotic imbalance and thirst are induced by the interference with fluid and
      electrolyte balance occurring during treatment. Changes in osmolarity due to
      alterations of plasma sodium concentration during hemodialysis strongly influence
      fluid distribution between extracellular and intracellular fluid volume.
      Increased sodium dialysate concentration induces fluid shift from the
      intracellular to the extracellular compartment. This shift leads to a more
      efficient ultrafiltration by increasing plasma refilling volume but also to an
      increased thirst. Treatment of hypotension, cramps and nausea with hypertonic
      saline solution leads also to a considerable retention of sodium. Profiling
      hemodialysis consists in deliberately changing ultrafiltration and dialysate.
      sodium in order to combine an efficient ultrafiltration with a balanced sodium
      handling and to prevent side-effects during treatment. Continuous measurement and
      control of blood volume seems to be the best method to prevent hypotensive
      episodes. Profiling of sodium should not be the cause of a positive sodium
      balance. The clinical benefits of sodium profiling to the patients have still to
      be proven.

PMID- 12074341
TI  - Psychophysiological comorbidity and computerized biofeedback.
AB  - Our previous research on basic and applied psychophysiology comprised the quantum
      model for subcellular brain processes, the psychosomatic health risk assessment
      and management, as well as the electrodermal biofeedback psychometrics and
      therapy. Based on this experience, in the present paper the stress-related
      psychophysiological disorders in patients dependent on hemodialysis and insulin
      are considered. The most frequent comorbid psychological disorders appeared to be
      anxiety and depression, and they are generally under-diagnosed and under-treated.
      It is concluded that the quality of life of these patients needs to be
      considerably enhanced. The application of biofeedback, as a complementary cost
      effective and non-invasive psychophysiological tool is recommended. In terms of
      ESAO vocabulary, this technique could be viewed as some kind of artificial
      ANS/CNS support. Simultaneously, the concept of biocompatibility may be viewed in
      a larger perspective as "psychobiocompatibility".

PMID- 12074342
TI  - Biodegradable polymeric matrices for bioartificial implants.
AB  - Biomaterials made of polymers, metals or their alloys, ceramics and their
      composites, are used as implants to restore or to replace the damaged soft and
      hard tissue/organ functions for an intended time period. Biomaterials made of
      synthetic materials are very simple materials compared to their natural
      counterparts, they only replace very simple functions of the damaged tissue
      during healing. Natural tissues have been used for both soft and hard repair and
      replacement, but they do have serious limitations such as: shortage of donor
      tissue, donor site morbidity, unpredictable resorption characteristics,
      immunogenic response, risk of disease transmission, and ethical limitations.
      Tissue engineering is a relatively new approach, in which healthy mammalian cells
      are used with supporting matrices, usually made of either natural or synthetic
      polymers as composite bioartificial implants. Primary cells, especially embryonic
      stem cells, cell lines, hybridomas, genetically modified cells are considered as
      potential sources for this application. Both closed and open matrices are used as
      support matrices. Nondegradable and biocompatible microcapsules and hollow fibers
      are utilized in closed systems, especially for immunoprotection of the
      transplanted cells. Biodegradable polymers, both natural and synthetic are used
      in the preparation of bioartificial implants carrying only autogenic cells.

PMID- 12074343
TI  - Testing protein permeability of dialysis membranes using SDS-PAGE.
AB  - BACKGROUND: Permeability of dialysis membranes for high molecular weight
      compounds should be similar to that of the glomerular membrane in order to remove
      uremic toxins like the human kidney does. In order to evaluate permeability of
      high-flux dialysis membranes SDS-PAGE is applied for examination of filtrate of
      dialysers during routine dialysis with different membranes. METHOD: SDS-PAGE
      analysis is performed with silver staining method according to the modification
      of Melzer (5) and consecutive laser densitometry. RESULTS: The protein pattern of
      filtrate from dialysis membranes is similar to that of the glomerular membrane
      containing IgG, transferrin, albumin, alpha-1-microglobulin, retinol binding
      protein and beta-2-microglobulin. Comparing different membranes there are
      considerable differences depending on cut-off, charge and adsorption capacity of
      the particular membrane. In all membranes tested permeability of proteins
      decreases during one treatment session. CONCLUSION: Protein permeability of high
      flux dialysis membranes is similar to the gloemerular membrane but modified
      according to pore-size, surface charge, adsorption and time on dialysis. In
      contrast to the glomerular membrane in each of the investigated membranes protein
      permeability decreases during function.

PMID- 12074344
TI  - Dialysis membranes today.
AB  - In recent years, hemodialytic therapies have evolved from the simple, diffusion
      dependent removal of small molecular weight substances from blood to advanced
      therapy modalities involving the convective removal of larger uremic sloutes. The
      clinical benefits of removal of substances such as beta2-microglobulin (beta2-m)
      have been reported by several authors: elimination of large-molecular weight
      "uremic toxins" is now widely accepted as being beneficial to the overall quality
      of life of patients. This trend would not have been possible without parallel
      technical developments, especially that of new membranes having more open pore
      structures resulting in higher sieving coefficients and increased hydraulic
      permeability. Not all polymer types are suitable for the manufacture of high-flux
      membranes required for convective therapies in which large fluid volumes are
      exchanged. Amongst the more important criteria are: the selected polymer must be
      able to undergo steam sterilisation, have high endotoxin retention capabilities,
      be versatile for the fabrication of a range of hydraulic permeabilities and, of
      course, have high blood compatibility. The aim of this paper is, firstly, to
      review the major membrane development phases over the last quarter of a century.
      Secondly, the suitability of current membrane materials to meet the
      aforementioned requirements will be examined. Thirdly, in view of the recent,
      rapid proliferation of polysulfone-based membranes, dialysis membranes of the
      polysulfone 'family' are placed under scrutiny; membranes of this class represent
      a significant portion of the product portfolio of dialyser manufacturers today,
      yet, few end-users are able to distinguish between the salient features of the
      respective products because of a combination of confusing membrane nomenclature,
      classification, tradenames and product claims.

PMID- 12074345
TI  - Heparin-coated versus uncoated Palmaz-Schatz stent in native coronary
      circulation. A randomized study with blind angioscopic assessment.
AB  - The increasing use of stenting to treat more complex lesions and highly
      thrombogenic situations still carries higher risk for subacute stent thrombosis.
      To assess new heparin-coated stents in a more stringent reality, 40 consecutive
      patients were randomized in 1:1 ratio to receive either heparin-coated (group 1,
      25 stents) or uncoated Palmaz-Schatz stents (group 2, 32 stents). The two groups
      were similar in baseline clinical, pre-and post-procedural angiographic and
      angioscopic characteristics. High pressure stent deployment without intravascular
      ultrasound guidance was used. All pts received antiplatelet agents alone. We
      applied serial angioscopy (baseline and on 7th day) to evaluate thrombus
      formation and quantitative coronary angiography (QCA) to define late (6 months,
      n=39, 100% the eligible pts) neointimal regrowth. There was one subacute stent
      thrombosis with subsequent acute myocardial infarction and death in the uncoated
      group. CONCLUSION: The implantation of heparin-coated stents in nonselected
      population is well tolerated and associated with no clinical or angioscopic
      evidence of new thrombus formation, resulting in favorable long-term clinical and
      angiographic outcome.

PMID- 12074346
TI  - Polymers in nephrology. Characteristics and needs.
AB  - Polymers employed as biomaterials in nephrology serve for different applications:
      they form membranes for dialysis and plasmapheresis, are used as materials for
      dialyser housings and as a potting mass for capillary membranes, they make up
      tubing-systems for extracorporeal circuits and - in the form of beads - act as
      parts of adsorber columns for hemoperfusion or immunoadsorption. However,
      generally speaking, many polymers have not yet been designed for their final
      application. To date, many polymers are still taken from the chemist's shelf
      according to their alleged performance properties or to their sterilisability.
      When used in medical application, polymers must show a high purity. Uncontrolled
      leaching of oligomers from the polymer backbone or of additives from or during
      the manufacturing process must be avoided. Blood and other body fluids are
      extremely effective in extracting any loosely bound polymers. During long-term
      application, e.g. in patients suffering from chronic diseases, these effects may
      lead to an accumulation of these compounds in circulating blood, tissue, or
      joints. Consequently, polymers should show an excellent biostability and not
      degrade during their ageing process. The amount of extractable material should be
      kept low in order to avoid inflammatory reactions. Polymers must have high blood
      compatibility in terms of minimized cell- and complement activation. Polymers for
      medical application should at best be able to stand high temperatures in order to
      survive steam sterilisation. If this is impossible, their release kinetics for
      residual quantities of sterilizing agents should be fast. Finally, protein
      adsorption should appear under controlled conditions, otherwise a reduced
      performance through protein adsorption will take place. Further, the uncontrolled
      activation of biochemical cascades, such as the coagulation, complement or
      contact phase cascade, following blood/material contact must be minimized. A
      final aspect has been recently made responsible for adverse patients reactions,
      the interaction between polymers and medicinal drugs. This drug/material
      interaction must be low, at best zero, apart form those situations, where a
      controlled drug-release is wanted. The chemical variety of polymers for medical
      application is large. However, all typical requirements cannot be met by one
      single polymer. Compromises have to be found between properties and application.
      Polymer selection for application in nephrology has always to be made under the
      premise of final application.

PMID- 12074347
TI  - Raising lipids acutely reduces baroreflex sensitivity.
AB  - Impaired baroreflex sensitivity (BRS) is associated with hypertension and
      cardiovascular risk. Lipid abnormalities accompanying insulin resistance may
      impair BRS. To test this, nine obese, dyslipidemic hypertensive and seven healthy
      normotensive individuals were studied. The BRS was measured during a
      phenylephrine infusion before and after nonesterified fatty acids (NEFAs) and
      triglycerides were raised for 1 h with an Intralipid and heparin infusion, ie,
      acute dyslipidemia. The obese group had higher values than lean controls for
      several components of the insulin resistance syndrome including blood pressure
      (BP) and heart rate, as well as fasting insulin, triglycerides, and NEFA. The BRS
      was lower in obese hypertensive subjects than healthy controls at baseline (P <
      .0001); BRS declined from 8.3 +/- 0.4 to 5.2 +/- 0.3 (P < .001) in obese
      hypertensive subjects and from 15.9 +/- 2.2 to 7.5 +/- 0.7 msec/mm Hg (P = .04)
      in controls with acute dyslipidemia. The reduction in BRS correlated with the
      rise in NEFAs (r = -0.59, P = .02) but not triglycerides (r = -0.07, P = NS).
      These observations indicate that elevating NEFAs acutely impairs BRS. The
      findings suggest that lipid abnormalities in obese hypertensives may contribute
      to elevated BP and increased cardiovascular events by impairing BRS.

PMID- 12074348
TI  - Greater intima-media thickness in the carotid bulb is associated with reduced
      baroreflex sensitivity.
AB  - The aim of this study was to evaluate the association between resting baroreflex
      sensitivity (BRS) and carotid intima-media thickness (IMT), a putative marker of
      subclinical atherosclerosis. Participants were 64 men and 18 women (median age,
      57 years; range, 40 to 70 years), who did not have a previous history of coronary
      artery disease or treatment for hypertension. Resting BRS was measured during a 9
      min baseline period using the noninvasive sequence technique; carotid IMT was
      subsequently determined using ultrasonography. Hierarchical multiple regression
      analyses showed that greater IMT in the carotid bulb (an area with a high density
      of baroreceptors) was associated with reduced BRS. These findings remained after
      adjusting BRS for resting mean arterial pressure, age, body mass index, gender,
      and smoking history, R2 = 0.06, P = .03. In contrast, IMT in the common and
      internal carotid regions (areas with presumably lower baroreceptor densities) did
      not account for a significant proportion of the variance in BRS. These results
      suggest that subclinical atherosclerosis, specifically in a region with high
      baroreceptor density, is associated with a reduced sensitivity of the baroreflex.

PMID- 12074350
TI  - Serum hepatocyte growth factor concentration is correlated with the forearm
      vasodilator response in hypertensive patients.
AB  - To evaluate the clinical importance of serum hepatocyte growth factor (HGF)
      concentration, we designed two clinical investigations. The first study analyzed
      the correlation between serum HGF concentration and clinical arterial stiffness
      or the vasodilator response to reactive hyperemia in hypertensive patients. The
      second study investigated the correlation between changes in serum HGF
      concentration and clinical arterial stiffness or reactive hyperemia during
      treatment with cilazapril or atenolol. A total of 210 hypertensive patients were
      analyzed in the first study, and 25 patients with essential hypertension were
      evaluated in the second study. Pulse wave velocity (PWV), strain gauge
      plethysmography, and serum HGF concentration were measured in the first study. We
      also evaluated these factors before and after treatment with either cilazapril
      (2.0 mg/day) or atenolol (25 mg/day) for 6 months in the second study. Serum HGF
      concentration was negatively correlated to reactive hyperemia in overall (r =
      0.434, P < .0001) and nontreatment (r = 0.452, P < .0001) hypertensive patients.
      Arterial stiffness was weakly related to serum HGF concentration (P < .05) after
      adjusting for age and mean blood pressure (BP). By multiple regression analysis,
      only serum HGF concentration showed a strong independent correlation with
      reactive hyperemia, age and mean BP with PWV. Moreover, a relationship between
      endothelium-dependent vasodilation and serum HGF concentration was observed
      during treatment with cilazapril or atenolol (r = 0.406, P < .005). These results
      suggest that in evaluation of serum HGF concentration, the forearm vasodilator
      response to reactive hyperemia and PWV might be useful for managing hypertension
      in patients who are receiving antihypertensive therapy.

PMID- 12074349
TI  - Chloride increases adrenergic receptor-mediated platelet and vascular responses.
AB  - BACKGROUND: We postulated that increasing intracellular chloride concentration
      ([Cl-]i) in human platelets would potentiate alpha2 adrenergic receptor (A2AR)
      mediated platelet aggregation, and that vascular reactivity would also be
      increased by raising [Cl-]i in blood vessels. We further hypothesized that
      ligands binding to the A2AR would increase [Cl-]i by stimulating carbonic
      anhydrase-dependent chloride/bicarbonate exchange. Because diuretics are potent
      inhibitors of carbonic anhydrase, we speculated that these agents inhibit
      platelet aggregation and vascular contractility through inhibition of chloride
      influx by decreasing carbonic anhydrase activity, and subsequently,
      chloride/bicarbonate exchange. The aim of this study was to test these
      hypotheses. METHODS: Platelet aggregation was measured by determining changes in
      optical density of platelet-rich plasma. Contractile responses to A2AR agonists
      were recorded in isolated vascular smooth muscle. The substances [Cl-]i and
      intracellular pH (pHi) were measured using microfluorometric methods. Carbonic
      anhydrase activity and chloride/bicarbonate exchange were determined by an in
      vitro assay based on the Stewart cycle. RESULTS: Increasing [Cl-]i potentiated
      platelet aggregation and vascular contractility, and epinephrine raised [Cl-]i by
      stimulating carbonic anhydrase-dependent chloride/bicarbonate exchange.
      Furthermore, diuretic-dependent inhibition of carbonic anhydrase activity
      decreased chloride/bicarbonate exchange. CONCLUSIONS: Our data support the
      concept that diuretics inhibit carbonic anhydrase activity and
      chloride/bicarbonate exchange in platelets and vascular smooth muscle. The
      ensuing reduction in [Cl-]i that is induced by diuretics in these tissues could
      play a role in reducing the effect of catecholamines on precipitating thrombotic
      stroke or myocardial infarction.

PMID- 12074351
TI  - Correlation between silent cerebral white matter lesions and left ventricular
      mass and geometry in essential hypertension.
AB  - BACKGROUND: It has been proposed that concentric left ventricular hypertrophy
      (LVH) is related to a worse degree of target organ damage in hypertensives with
      this feature than in those without. Moreover, the presence of cerebral white
      matter lesions (WMLs) is considered to be an early marker of brain damage in
      essential hypertension. The aim of this study was to assess the association
      between the presence of silent WMLs and left ventricular mass and geometry in
      middle-aged individuals with hypertension that had never been treated. METHODS: A
      total of 62 patients (39 men, 23 women, aged 50 to 60 years, mean age 54.4 +/-
      3.2 years) with never-treated essential hypertension and without clinical
      evidence of target organ damage were studied. All patients underwent brain
      magnetic resonance imaging and were classified into two groups according to the
      presence or absence of WMLs. Echocardiography measuring posterior wall thickness
      (PWT), interventricular septum thickness (IVST) and left ventricular end
      diastolic diameter (LVEDD) was also performed. Left ventricular mass index (LVMI)
      was calculated using the Penn convention criteria, and relative wall thickness
      ratio (RWT) was estimated by the standard formula: 2 x PWT/LVEDD. RESULTS:
      Hypertensive patients with WMLs exhibited significantly higher PWT, IVST, LVMI,
      and RWT when compared with hypertensive patients without WMLs. In addition, 23 of
      26 hypertensive patients with WMLs showed echocardiographic criteria for LVH that
      was significantly higher than that observed in hypertensive patients without WMLs
      (21 of 36; P = .01). Concentric hypertrophy (LVH and RWT > or = 0.45) was present
      in 14 hypertensive patients with WMLs and in only four patients without WMLs (P =
      .002). CONCLUSION: There is a close association between cerebral WMLs and
      concentric LVH in asymptomatic middle-aged hypertensive patients, independent of
      blood pressure values.

PMID- 12074352
TI  - Left ventricular diastolic function in physiologic and pathologic hypertrophy.
AB  - BACKGROUND: Patients with hypertensive heart disease and left ventricular
      hypertrophy demonstrate an impaired left ventricular diastolic filling pattern.
      The aim of this study was to find out whether physiologic left ventricular
      hypertrophy induced by endurance training causes disturbances in left ventricular
      systolic and diastolic filling. METHODS: We examined 49 athletes with left
      ventricular (LV) hypertrophy due to endurance training, 49 patients with LV
      hypertrophy due to arterial hypertension, and 26 untrained healthy control
      subjects by conventional echocardiography. Parameters of LV diastolic filling
      using pulse wave and color flow Doppler were also assessed. RESULTS: All three
      study groups showed normal fractional shortening and mid-wall fractional
      shortening. Conventional echocardiography revealed a higher LV muscle mass index
      in the two study groups compared with the controls (athletes, 99 +/- 10 g;
      hypertensive patients, 95 +/- 11 g: controls: 52 +/- 7 g; P < .01 for athletes
      and hypertensive patients). In patients with arterial hypertension, a diastolic
      dysfunction consisting of a delayed relaxation pattern with a decrease in maximal
      early velocity of diastolic filling (0.44 +/- 0.1 m/sec) and a compensatory
      increase of the maximal late velocity of diastolic filling (0.53 +/- 0.1 m/sec)
      was demonstrated. In athletes with physiologic LV hypertrophy, a normal LV
      diastolic filling pattern was documented. CONCLUSIONS: Doppler echocardiographic
      parameters of LV diastolic function can be of diagnostic importance for
      discrimination between pathologic and physiologic LV hypertrophy.

PMID- 12074353
TI  - Ambulatory blood pressure and coronary artery calcification in middle-aged and
      younger adults.
AB  - BACKGROUND: The objective of this study was to investigate relationships between
      blood pressure (BP) determined by ambulatory monitoring and coronary artery
      calcification (CAC) determined by electron beam computed tomography (EBCT) in
      middle-aged and younger adults without symptoms of coronary artery disease.
      METHODS: Measures of office and ambulatory BP were analyzed in 298 asymptomatic
      adults (134 women and 164 men) from the white population of Rochester, MN, who
      were 20 to 60 years old (mean +/- SD, 40 +/- 9 years). For the ambulatory BP
      measurements, the active period of the day was defined as the daytime, out-of-bed
      hours and the inactive period as the nighttime, in-bed hours. Logistic regression
      was used to assess whether ambulatory measures of BP influenced the probability
      of having CAC detected by EBCT. RESULTS: After adjusting for sex, age, and office
      measures of BP, ambulatory diastolic BP during the active and inactive periods
      were each statistically significant additional predictors of the probability of
      having CAC. Similarly, after adjusting for sex, age, and ambulatory systolic BP,
      ambulatory diastolic BPs during each period were also statistically significant
      additional predictors of the probability of having CAC. In contrast, measures of
      ambulatory systolic BP, pulse pressure, and diurnal dipping of BP levels from the
      active to the inactive period did not make statistically significant additional
      contributions to the probability of having CAC. CONCLUSION: These findings
      emphasize the role that the hemodynamic stress of diastolic BP may play in the
      early development of atherosclerotic coronary artery disease.

PMID- 12074354
TI  - A longitudinal study of ethnic differences in ambulatory blood pressure patterns
      in youth.
AB  - BACKGROUND: Many studies demonstrated an ethnic difference in ambulatory blood
      pressure (BP) patterns. We examined: 1) the stability of this difference; 2)
      demographic and anthropometric characteristics that predict the difference over 2
      years; and 3) the clinical significance of the difference. METHODS: Recordings
      were performed 2 years apart on 94 African American and 92 European American
      youths with a positive family history of hypertension, aged 14 +/- 2 years at
      initial testing. RESULTS: African Americans had higher nighttime systolic BP
      (SBP) on the initial (109 +/- 9 v 105 +/- 8 mm Hg; P < .001) and follow-up (110
      +/- 10 v 105 +/- 8 mm Hg; P < .0001) visits despite similar daytime SBP. This was
      associated with greater left ventricular mass/height2.7 (LVM/height2.7) during
      the initial (31 +/- 8 v 28 +/- 6 g/height2.7; P < .01) and follow-up (32 +/- 8 v
      28 +/- 8 g/height2.7; P < .02) visits. Sex accounted for 17% (P < .0001) of the
      variance of follow-up daytime SBP in African Americans, and age for an additional
      10% (P < .001). In comparison, initial height accounted for 11% (P < .001) of the
      variance in European Americans. Sex accounted for 18% (P < .0001) of the variance
      of follow-up nighttime SBP in African Americans, age for an additional 12% (P <
      .0001), and initial LVM/height2.7 an additional 6% (P < .02). In contrast, sex
      accounted for 13% of the variance of follow-up nighttime SBP in European
      Americans, and initial height accounted for an additional 8% (P < .004).
      CONCLUSIONS: The pattern of higher nighttime BP despite similar daytime BP in
      African Americans is stable over time, with sex as the most important predictor
      of nighttime BP in both groups. This study provides confirmatory data on the
      clinical significance of the differences.

PMID- 12074355
TI  - Neurohumoral characteristics of older hypertensive patients with abnormal
      nocturnal blood pressure dipping.
AB  - Abnormal patterns of diurnal blood pressure (BP) variation have been reported to
      be related to advanced target organ damage and poor cardiovascular prognosis.
      However, the neurohumoral characteristics of patients with such variation have
      not been fully investigated. We measured BP and plasma levels of neurohumoral
      factors (norepinephrine [NE], epinephrine, renin, and arginine vasopressin [VP])
      during the 70 degree head-up tilt test (10 min supine and 15 min tilting) in 120
      older subjects (mean age 71 years) who had sustained hypertension as determined
      by ambulatory BP monitoring. They who were subclassified according to the
      nocturnal systolic BP fall as follows: 28 extreme dippers with >20% nocturnal BP
      fall; 78 dippers with >0% but <20% fall; and 14 nondippers with <0% fall. Plasma
      renin activity (r = 0.22, P = .02) and VP level (r = 0.36, P < .0001) after
      tilting were positively associated with the nocturnal systolic BP fall. Plasma NE
      levels were significantly higher in nondippers than in dippers in both the supine
      and tilting positions (supine 519 v 315 pg/mL, P = .001; tilting 803 v 550 ng/mL,
      P < .01), whereas the increase of NE induced by tilting was comparable in the two
      groups. Plasma renin activity in both the supine and tilting positions was
      comparable in the three groups, but the increase of this activity caused by
      tilting was less marked in the nondippers than in the extreme dippers (0.05 v
      0.26 ng/mL/min, P = .02) and dippers (0.21 ng/mL/min, P = .07). Plasma VP was
      markedly increased after tilting in the extreme dippers compared with dippers
      (3.8 v 2.6 pg/mL, P < .001) and nondippers (v 2.0 pg/mL, P < .001), whereas the
      levels in the supine position were comparable in the three groups (2.0 pg/mL for
      extreme dippers, 1.9 pg/mL for dippers, 1.6 pg/mL for nondippers). In conclusion,
      diurnal BP variation in elderly hypertensive individuals was significantly
      associated with neurohumoral factors regulating circulating blood volume.
      Increased VP after tilting in extreme dippers might counteract reduced
      circulating blood volume, whereas nondippers appear to have alpha- and beta
      adrenergic subsensitivity that may be induced by their chronic exposure to high
      NE levels.

PMID- 12074356
TI  - The relationship between body mass index and pulse pressure in older adults with
      isolated systolic hypertension.
AB  - BACKGROUND: Many longitudinal studies have reported excess cardiovascular
      mortality among lean hypertensive subjects, suggesting that obesity may mitigate
      the cardiovascular risk of hypertension. Available evidence also suggests that in
      middle-aged and older hypertensive subjects, pulse pressure may be a better
      predictor of cardiovascular complications. However, there are limited data on the
      relationship between body mass index (BMI) and pulse pressure. METHODS: Using
      data from the Third National Health and Nutrition Examination Survey we assessed
      the convergence validity of pulse pressure as a predictor of cardiovascular
      complications and examined the relationship between BMI and pulse pressure in
      1192 older adults with isolated systolic hypertension who were not receiving
      blood pressure medicine. RESULTS: There was a good concordance between high pulse
      pressure and most of the selected cardiovascular risk factors examined in this
      study. Pulse pressure is higher in the lean (BMI < 25) than in the overweight
      (BMI > or = 25; 79 mm Hg vs 74 mm Hg, P < .001) and decreases significantly from
      82 mm Hg in the first BMI quintile to 76 mm Hg in the fifth BMI quintile. Pulse
      pressure continues to decrease with increasing BMI until the index exceeds 30.1.
      This negative correlation persists in a multivariate model with statistical
      adjustment for age, sex, diabetes mellitus, and hypercholesterolemia. CONCLUSION:
      The inverse relation between BMI and pulse pressure observed here may help to
      explain previous reports of increased cardiovascular risk among lean versus obese
      subjects with isolated systolic hypertension.

PMID- 12074357
TI  - A comparison of candesartan, felodipine, and their combination in the treatment
      of elderly patients with systolic hypertension.
AB  - Monotherapy frequently does not cause adequate blood pressure (BP) reduction and
      goal BP is not achieved. This double-blind, randomized, crossover, placebo
      controlled study investigated, using a factorial design, the interaction between
      a dihydropyridine calcium channel blocking drug (felodipine 5 mg) and an
      angiotensin type I receptor blocking drug (candesartan 16 mg) on the control of
      BP as assessed by 24-h ambulatory monitoring. A total of 31 elderly patients with
      systolic hypertension completed all four arms of the study. Candesartan and
      felodipine lowered mean 24-h BP to a similar extent (candesartan 12.2 +/- 2.6/7.5
      +/- 1.8; felodipine 11.9 +/- 2.2/5.7 +/- 1.4 mm Hg). The combination lowered it
      by 21.0 +/- 2.1/11.2 +/- 1.2 mm Hg, and this fall was significantly greater than
      with either of the monotherapies (P < .005) and was fully additive with no
      interactive term. The responder rate with the combination (90%) was greater than
      with candesartan (61%) or felodipine (55%). Microalbuminuria or proteinuria was
      present in 12 of 31 patients at randomization despite previous BP control.
      Candesartan and the combination both reduced urinary albumin excretion. Albumin
      excretion was not reduced by felodipine despite BP control similar to that
      achieved with candesartan. Side effects were infrequent and were fewer on the
      combination than on placebo or on the monotherapies. The combination of
      felodipine 5 mg and candesartan 16 mg has additive effects on BP in elderly
      patients with systolic hypertension. The combination was well tolerated and is
      suitable for use in patients who do not have an adequate response to monotherapy.

PMID- 12074358
TI  - Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in
      a practice-based setting.
AB  - BACKGROUND: Community-based studies are conducted to determine the degree to
      which therapeutic interventions will succeed in real world settings. This large
      practice-based clinical trial assessed the efficacy and tolerability of fixed
      dose combination therapy with amlodipine/benazepril, compared with amlodipine
      monotherapy, in patients with mild-to-moderate hypertension. METHODS:
      Hypertensive patients currently taking amlodipine were selected based on one of
      two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP
      [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or =
      90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10
      mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In
      group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A
      secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group
      2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema
      improved during therapy with amlodipine/benazepril when compared with amlodipine
      monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at
      baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence
      interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean
      sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm
      Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%)
      experienced some improvement in edema compared with baseline levels. CONCLUSIONS:
      Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and
      effective for patients who experienced either inadequate BP control or edema with
      amlodipine monotherapy.

PMID- 12074359
TI  - Effects of omapatrilat on the renin-angiotensin system in salt-sensitive
      hypertension.
AB  - The contribution of angiotensin-(1-7) [Ang-(1-7)] to the antihypertensive actions
      of omapatrilat, a novel vasopeptidase inhibitor, was evaluated in 22 salt
      sensitive, low renin, hypertensive subjects as a substudy of a multicenter
      randomized, double-blind, parallel study of 4 weeks duration. A total of 25 other
      subjects received lisinopril as the active control. Omapatrilat (40 mg) produced
      sustained control of blood pressure (BP) (as assessed by 24-h ambulatory BP
      measurements) that was significantly greater than that produced by 20 mg daily of
      lisinopril. The antihypertensive response to either drug was accompanied by
      similar sustained inhibition of angiotensin converting enzyme activity. Plasma
      levels of angiotensin I (Ang I), angiotensin II (Ang II) and Ang-(1-7) were not
      altered by treatment with either omapatrilat or lisinopril, even though both
      regimens produced a modest rise in plasma renin activity. In contrast, urinary
      excretion rates of Ang I and Ang-(1-7) but not Ang II increased significantly
      throughout the dosing period of subjects who were given omapatrilat, whereas the
      smaller antihypertensive response produced by lisinopril had a smaller and
      transient effect on increasing urinary excretion rates of Ang-(1-7). Omapatrilat,
      being a single molecule inhibiting neutral endopeptidase and converting enzyme
      simultaneously, controlled salt-sensitive hypertension by a mechanism that was
      associated with sustained increases in urinary Ang-(1-7) excretion. We suggest
      that Ang-(1-7) may be a component of the mechanisms by which omapatrilat induces
      an antihypertensive response in salt sensitive hypertension.

PMID- 12074360
TI  - Identification of a functional Na+/Mg2+ exchanger in human trophoblast cells.
AB  - BACKGROUND: Ionized magnesium levels are elevated in fetal blood compared with
      maternal blood, suggesting that the placenta may possess an active transport
      mechanism for magnesium. In the present study, we sought to determine the
      existence of an active transport mechanism for magnesium in the placenta using
      cultured trophoblast cells. METHODS: Using choriocarcinoma cells as a model
      system, we attempted to demonstrate the presence of a functional Na+/Mg2+
      exchanger. Human choriocarcinoma JEG-3 cells cultured on glass coverslips were
      loaded with MAG-Fura 2-AM (5 micromol/L x 30 min) to spectrofluorometrically
      assess kinetics of intracellular magnesium ([Mg2+]i). Cells were superfused with
      various concentrations of Na+, Mg2+, Ca2+ and imipramine, a blocker of
      erythrocyte Na/Mg exchange. [Mg2+]i calibration was determined via Triton X-100
      and EDTA. RESULTS: Sequential lowering of extracellular Na+ caused progressively
      larger, transient increases in [Mg2+]i. These transient changes in [Mg2+]i were
      completely dependent on [Mg]o but was independent of extracellular calcium
      ([Ca]o). Although acute imipramine did not alter basal [Mg2+]i, imipramine
      eliminated the return-to-basal phase of the [Mg2+]i transient induced by low
      sodium medium. Increasing extracellular magnesium ([Mg]o) caused stepwise
      increases in [Mg2+]i. CONCLUSIONS: The JEG-3 cells appear to possess a functional
      Na/Mg exchanger that functions to maintain low [Mg2+]i in cytotrophoblast cells.
      In addition, [Mg2+]i is acutely regulated by [Mg]o. Because placental
      trophoblasts are sites of maternal-fetal ion exchange, and [Mg]o is altered in
      preeclampsia, derangements in or modulation of this exchanger may contribute to
      complications of pregnancy such as pregnancy-induced hypertension, pre-eclampsia,
      and preterm labor.

PMID- 12074361
TI  - Beneficial effects on blood pressure and lipid profile of programmed exercise
      training in subjects with white coat hypertension.
AB  - BACKGROUND: Patients with white coat hypertension comprise a substantial portion
      of the hypertensive population. Previous reports have shown that moderate
      intensity regular exercise training in patients with mild hypertension usually
      reduces blood pressure (BP), but there is a lack of data regarding individuals
      with white coat hypertension. This study was performed to evaluate whether
      programmed exercise was effective in reducing BP in patients with white coat
      hypertension and whether it also had beneficial effects on other biochemical
      parameters. METHODS: A total of 42 patients (23 men and 19 women) with white coat
      hypertension (mean 24-h ambulatory BP 119.2 +/- 6.6/78.3 +/- 5.8 mm Hg) were
      divided randomly into two groups: control (n = 20) (no exercise), and moderate
      intensity exercise (n = 22). The training group exercised three times per week at
      the prescribed exercise intensity using a treadmill exercise program. Blood
      pressure, heart rate, and biochemical parameters were monitored every 4 weeks for
      12 weeks. RESULTS: Significant reductions in clinic and ambulatory BPs were seen
      in the exercise group after only 4 weeks regular exercise training and these
      persisted over the 12-week study. The mean maximal reductions in clinic BP were
      11 mm Hg for systolic and 5 mm Hg for diastolic pressure. Significant reductions
      were found in plasma total cholesterol (-6.1%), low-density lipoprotein
      cholesterol (LDL-C) (-14.1%), and triglyceride (-11.4%). Elevation of high
      density lipoprotein cholesterol (HDL-C) (+11.2%) was also noted. CONCLUSIONS:
      These data, which are clinically significant, suggest that 12 weeks of exercise
      training can result in successful reduction of BP and favorable changes in the
      lipid profile that would be beneficial to patients with white coat hypertension.

PMID- 12074362
TI  - The ASH Specialists Program: a progress report. American Society of Hypertension.

PMID- 12074363
TI  - A comparative crossover evaluation of amlodipine and nifedipine GITS before and
      after a missed dose: 48-h blood pressure profiles.

PMID- 12074364
TI  - Oligonucleotide conjugates as potential antisense drugs with improved uptake,
      biodistribution, targeted delivery, and mechanism of action.
AB  - This review summarizes the effect of conjugating small molecules and large
      biomacromolecules to antisense oligonucleotides to improve their therapeutic
      potential. In many cases, favorable changes in pharmacokinetic and
      pharmacodynamic properties were observed. Opportunities exist to change the
      terminating mechanism of antisense action or to enhance the RNase H mode of
      action via conjugate formation.

PMID- 12074365
TI  - Cell-dependent differential cellular uptake of PNA, peptides, and PNA-peptide
      conjugates.
AB  - Peptide nucleic acid (PNA) oligomers were conjugated to cell-penetrating
      peptides: pAnt, a 17-residue fragment of the Drosophila protein Antennapedia, and
      pTat, a 14-amino acid fragment of HIV protein Tat. A 14-mer PNA was attached to
      the peptide by disulfide linkage or by maleimide coupling. The uptake of
      (directly or indirectly, via biotin) fluorescein-labeled peptides, PNAs, or PNA
      peptide conjugates was studied by fluorescence microscopy, confocal laser
      scanning microscopy, and fluorometry in five cell types. In SK-BR-3, HeLa, and
      IMR-90 cells, the PNA-peptide conjugates and a T1, backbone-modified PNA were
      readily taken up (2 microM). The PNA was almost exclusively confined to vesicular
      compartments in the cytosol. However, the IMR-90 cells also showed a weak diffuse
      staining of the cytoplasm. In the U937 cells, we observed a very weak and
      exclusively vesicular staining with the PNA-peptide conjugates and the T(lys)
      modified PNA. No evident uptake of the unmodified PNA was seen. In H9 cells, both
      peptides and the PNA-peptide conjugates quickly associated with the membrane,
      followed by a weak intracellular staining. A cytotoxic effect resulting in
      artificial staining of the cells was observed with fluoresceinated peptides and
      PNA-peptide conjugates at concentrations above 5-10 microM, depending on cell
      type and incubation time. We conclude that uptake of PNAs in many cell types can
      be achieved either by conjugating to certain peptides or simply by charging the
      PNA backbone using lysine PNA units. The uptake is time, temperature, and
      concentration dependent and mainly endocytotic. Our results also show that proper
      controls for cytotoxicity should always be carried out to avoid misinterpretation
      of visual data.

PMID- 12074366
TI  - Pharmacokinetics and tissue distribution of a peptide nucleic acid after
      intravenous administration.
AB  - Peptide nucleic acids (PNAs) are DNA analogs that hybridize to complementary
      nucleic sequences with high affinity and stability. In our previous work, we
      showed that a PNA complementary to a 12-base pair (bp) sequence of the coding
      region of the rat neurotensin receptor (rNTR1) mRNA is effective in significantly
      blocking a rat's central responses to neurotensin (NT), even when the PNA is
      injected intraperitoneally (i.p.). Using a novel gel shift detection assay to
      detect PNA, we have now used this same PNA sequence to derive its pharmacokinetic
      variables and its tissue distribution in the rat. The PNA has a distribution half
      life of 3 +/- 3 minutes and an elimination half-life of 17 +/- 3 minutes. The
      total plasma clearance and volume of distribution of this PNA were 3.4 +/- 0.9
      ml/min x kg and 60 +/- 30 ml/kg. Two hours after dosing, the PNA was found at
      detectable but low levels in all organs examined-in order of decreasing
      concentration: kidney, liver, heart, brain, and spleen. Approximately 90% of the
      PNA dose was recovered as unchanged parent compound in the urine 24 hours after
      administration.

PMID- 12074367
TI  - Antisense-mediated inhibition of ICAM-1 expression: a therapeutic strategy
      against inflammation of human periodontal tissue.
AB  - Periodontal diseases, such as gingivitis and periodontitis, are caused by a mixed
      infection by several types of bacteria in the dental plaque, causing a chronic
      inflammation of the gingival mucosa. Inflammatory processes in conjunction with
      immune responses to bacterial attacks are generally protective. In profound
      periodontitis, however, hyperresponsiveness and hypersensitivity of the immune
      system are counterproductive because of the destruction of the affected
      periodontal connective tissues. The intercellular adhesion molecule type 1 (ICAM
      1) plays a key role in the onset and manifestation of inflammatory responses.
      Thus, inhibition of ICAM-1 expression could be of therapeutic relevance for the
      treatment of destructive periodontitis. Here, antisense oligonucleotides (AS-ON)
      directed against ICAM-1 suppress protein expression and mRNA levels specifically
      and effectively in primary human endothelial cells of different tissue origin.
      Moreover, downregulation of ICAM-1 expression is also observed in AS-ON
      transfected inflamed gingival mucosal tissue of patients with periodontal
      diseases. This work strongly suggests exploiting the local topical application of
      ICAM-1-directed AS-ON as a therapeutic tool against inflammatory processes of the
      human gingiva.

PMID- 12074368
TI  - Carboranyl oligonucleotides: 4. synthesis and physicochemical studies of
      oligonucleotides containing 2'-O-(o-carboran-1-yl)methyl group.
AB  - Boronated oligonucleotides are potential candidates for antisense oligonucleotide
      technology (AOT), boron neutron capture therapy (BNCT), and as tools in molecular
      biology. A method was developed for the solid phase synthesis of oligonucleotides
      containing 2'-O-(o-carboran-1-yl-methyl) (2'-CBM) group. Synthesis was performed
      using a standard beta-cyanoethyl cycle and automated DNA synthesizer. Manual
      steps were performed for the insertion of a modified monomer bearing the 2'-CBM
      group. Several tetradecanucleotides complementary to DNA-HCMV, and bearing 2'-CBM
      modification near the 3'-end or 5'-end or in the middle of the oligonucleotide
      chain were synthesized. The resulting oligomers were characterized by
      polyacrylamide gel electrophoresis (PAGE), reverse phase high-performance liquid
      chromatography (RP-HPLC), matrix-assisted laser desorption ionization mass
      spectrometry (MALDI-MS) and ultraviolet spectroscopy (UV), circular dichroism
      (CD), and melting temperature (Tm) measurements. Tm of duplexes formed between 2'
      CBM-modified tetradecanucleotides and complementary DNA and RNA template were
      compared with those formed by the unmodified oligonucleotide and complementary
      sequence. The stability of 2'-CBM oligonucleotides in the presence of
      phosphodiesterase I from Crotalus atrox venom and in human serum was studied.
      Oligonucleotides bearing the 2'-CBM group are characterized by increased
      resistance to enzymatic digestion, increased lipophilicity, and the ability to
      form stable duplexes with complementary templates.

PMID- 12074369
TI  - Evidence for sequence-dependent and reversible nonspecific effects of PS-capped
      antisense treatment after intracerebral administration.
AB  - Phosphorothioate (PS)-capped phosphodiester (PE) oligodeoxynucleotides (ODNs)
      were used to determine whether the dopamine-dependent locomotor-stimulant effect
      of nicotine is mediated via a4 subunit-containing nicotinic receptors. To this
      end, rats received direct intraventral tegmental area infusion of a4 antisense
      via osmotic minipump, and their locomotor response to nicotine (0.2 mg/kg, s.c.)
      was tested. Eight antisense ODNs were screened, but only one inhibited nicotine
      induced locomotion. This inhibition was reversible and selective, insofar as
      basal (saline) activity was unaffected, and a mismatch ODN was without effect.
      However, antisense treatment also caused sequence-dependent toxic effects,
      including neuronal degeneration in the ventral tegmental area, dopaminergic
      denervation, and weight loss. We conclude that despite previous reports, PS
      capped PE-ODNs can cause severe neurotoxicity on chronic infusion into brain
      tissue. Moreover, sequence dependence and temporal reversibility, two generally
      accepted criteria of antisense action, may sometimes reflect the occurrence of
      toxic effects and resultant functional compensation.

PMID- 12074370
TI  - Are changes in beliefs and attitudes about sleep related to sleep improvements in
      the treatment of insomnia?
AB  - Dysfunctional beliefs and attitudes about sleep are presumed to play an important
      mediating role in perpetuating insomnia. The present study evaluated the impact
      of cognitive-behavioral and pharmacological treatments for insomnia on sleep
      related beliefs and attitudes and the relationship between those changes and
      sleep improvements. The participants were older adults with chronic and primary
      insomnia. They received cognitive-behavior therapy (CBT), pharmacotherapy (PCT),
      combined CBT+PCT (COMB), or a medication placebo (PLA). In addition to daily
      sleep diaries and sleep laboratory measures, the participants completed the
      dysfunctional beliefs and attitudes about sleep scale (DBAS) at baseline and
      posttreatment, and at 3-, 12- and 24-month follow-up assessments. The results
      showed that CBT and COMB treatments produced greater improvements of beliefs and
      attitudes about sleep at posttreatment than PCT and PLA. Reductions of DBAS
      scores were significantly correlated with improvements of sleep efficiency as
      measured by daily sleep diaries and by polysomnography. In addition, more
      adaptive beliefs and attitudes about sleep at posttreatment were associated with
      better maintenance of sleep improvements at follow-ups. These findings highlight
      the importance of targeting sleep-related beliefs and attitudes in the treatment
      of insomnia.

PMID- 12074371
TI  - Three traditional and three new childhood anxiety questionnaires: their
      reliability and validity in a normal adolescent sample.
AB  - The current study examined the psychometrics of three traditional [i.e., the
      trait anxiety version of the State-Trait Anxiety Inventory for Children (STAIC),
      the Revised Children's Manifest Anxiety Scale (RCMAS), and the Fear Survey
      Schedule for Children - Revised (FSSC-R)] and three new childhood anxiety scales
      [the Multidimensional Anxiety Scale for Children (MASC), the Screen for Child
      Anxiety Related Emotional Disorders (SCARED), and the Spence Children's Anxiety
      Scale (SCAS)] in a large sample of normal adolescents (N=521). Childhood anxiety
      scales were generally found to be reliable in terms of internal consistency.
      Furthermore, evidence was obtained for the convergent and divergent validity of
      the various anxiety questionnaires. That is, anxiety questionnaire scores were
      found to be substantially intercorrelated. Particularly strong associations were
      found between total scores of the STAIC and the RCMAS, total scores of the SCARED
      and the SCAS, and between subscales that intend to measure specific categories of
      anxiety symptoms. Childhood anxiety questionnaires were substantially connected
      to an index of depression, although correlations among anxiety questionnaires
      were generally higher than those between anxiety scales and a measure of
      depression.

PMID- 12074372
TI  - Clinical perfectionism: a cognitive-behavioural analysis.
AB  - This paper reviews the characteristics of clinical perfectionism and proposes a
      new definition of the phenomenon. It is suggested that the defining feature of
      clinically significant perfectionism is the overdependence of self-evaluation on
      the determined pursuit (and achievement) of self-imposed personally demanding
      standards of performance in at least one salient domain, despite the occurrence
      of adverse consequences. It is suggested that such clinical perfectionism is
      maintained by the biased evaluation of the pursuit and achievement of personally
      demanding standards. Specifically, it is suggested that people with perfectionism
      react to failure to meet their standards with self-criticism. If they do meet
      their standards, the standards are re-evaluated as being insufficiently
      demanding. Anorexia nervosa and bulimia nervosa are considered to have a
      particular relationship to perfectionism, with both disorders often being direct
      expressions of perfectionism. Under these circumstances self-evaluation is
      dependent on the pursuit and attainment of personally demanding standards in the
      domain of control over eating, shape and weight. The implications of this
      analysis for research and practice are considered.

PMID- 12074373
TI  - Directed forgetting in obsessive-compulsive disorder: replication and extension.
AB  - Previous research indicates that patients with obsessive-compulsive disorder
      (OCD) show impaired ability to forget negative material (Behav Res Ther 34 (1996)
      633). The present study was intended to replicate and extend these findings by
      separating emotional valence from personal relevance, using idiographic stimulus
      selection to control for heterogeneity of OCD concerns, and the addition of an
      anxious control group. We used a directed forgetting paradigm, in which
      participants were instructed to either remember or forget a series of words. No
      differences in impairment were found among the groups during a free recall test,
      in which they were asked to recall both "remember" and "forget" words. However,
      during a recognition test, OCD patients showed greater impaired forgetting for
      OCD-relevant words than did nonanxious and anxious controls. Valence of words did
      not emerge as a contributing factor to impaired forgetting.

PMID- 12074374
TI  - Self-help and long-term behavior therapy for obesity.
AB  - The Trevose Behavior Modification Program, a self-help group offering continuing
      care for obesity, has recently been shown to produce large long-term weight
      losses. The present study aimed to replicate this finding across different
      settings and participants, assessing the weight losses and attrition rates of 128
      participants in three Trevose program satellite groups that used the same
      treatment procedures and manual as the central Trevose group. The satellite
      groups' results closely paralleled those of the Central Group. Mean intent-to
      treat weight loss, or final losses recorded for all participants regardless of
      their treatment termination date, was 13.7 +/- 0.7% of initial body weight (1.8
      +/- 0.7 kg). At two years, 43.8% of participants remained in treatment, having
      lost a mean of 19.0 +/- 0.8% of their body weight (16.2 +/- 1.0 kg); at five
      years, 23.4% remained, having lost 18.4 +/- 1.1% of body weight (15.6 +/- 1.5
      kg). These results demonstrate that the Trevose model of weight control,
      combining self-help and continuing care, can be extended and disseminated to
      other settings, with potentially significant public health consequences.

PMID- 12074375
TI  - Religiousness and obsessive-compulsive cognitions and symptoms in an Italian
      population.
AB  - Fifty-four individuals with a high degree of religiosity, 47 with a medium degree
      of religiosity and 64 with low religiosity completed anonymously the Italian
      versions of well-established measures of obsessive-compulsive (OC) cognitions and
      symptoms, depression and anxiety. After controlling for anxiety and depression,
      religious groups scored higher than individuals with a low degree of religiosity
      on measures of obsessionality, overimportance of thoughts, control of thoughts,
      perfectionism and responsibility. Moreover, measures of control of thoughts and
      overimportance of thoughts were associated with OC symptoms only in religious
      subjects. It is concluded that religion might play a role in obsessive-compulsive
      disorder phenomenology. Additional research is warranted because it is plausible
      that only a few aspects of religious teachings (e.g., inflexibility and
      prohibition) are linked to OC phenomena.

PMID- 12074376
TI  - Religious obsessions and compulsions in a non-clinical sample: the Penn Inventory
      of Scrupulosity (PIOS).
AB  - The present investigation reports on the development and psychometric evaluation
      of the Penn Inventory of Scrupulosity (PIOS), a 19-item self-report scale
      measuring religious obsessive-compulsive symptoms. Factor analysis yielded a two
      factor solution with the first subscale measuring fears about having committed
      sin, and the second measuring fears concerning punishment from God. Using a
      sample of college students, the PIOS was shown to be internally consistent and
      possess good convergent and discriminant validity. Highly devout participants
      evidenced higher scores on both PIOS subscales, but devout Jews evidenced fewer
      fears of sin and punishment from God compared to devout Protestants or Catholics.
      The PIOS has utility both as a research and clinical tool.

PMID- 12074377
TI  - The Anxiety Sensitivity Index for Children: factor structure and relation to
      panic symptoms in an adolescent sample.
AB  - This study examines the factor structure underlying the Anxiety Sensitivity Index
      for Children (ASIC. J Anxiety Disord, 12 (1998) 307) in an adolescent sample.
      Three-hundred-and-eight adolescents, aged 12 to 18, completed the ASIC and
      measures of anxiety and depression. Factor analysis of the ASIC items resulted in
      a two-factor structure that is similar to that reported by Laurent et al. These
      two factors included a physical concerns dimension and a mental concerns
      dimension similar to those found in studies of adult anxiety sensitivity.
      Subscales measuring these two factors demonstrated concurrent validity, showing
      particularly close associations with measures of panic symptoms. In addition,
      both of these subscales showed incremental validity in predicting panic symptoms
      after controlling for the other anxiety sensitivity subscale and a measure of
      depression. These results provide evidence that the anxiety sensitivity construct
      is applicable during adolescence and support the use of the ASIC.

PMID- 12074378
TI  - Self-reported problems: a comparison between PTSD-diagnosed veterans, their
      spouses, and clinicians.
AB  - This study investigated self-reported problems in a sample of help-seeking
      Vietnam veterans, comparing the veteran's own view with clinician and spouse
      perspectives, with the aim of examining convergence in reports across different
      informants. Veterans with PTSD (N = 459) were asked to list and rate their five
      most serious problems. Spouses and treating clinicians completed the same
      questionnaire in relation to the veteran. Rates of endorsement for each problem
      area, and levels of agreement between raters, were calculated. Veterans, spouses,
      and clinicians were all likely to rate anger as a high priority, with veterans
      also likely to nominate anxiety and depression. Spouses were likely to nominate
      more observable behavioural problems such as interpersonal difficulties and
      avoidance, while clinicians were likely to nominate indications of
      psychopathology, such as anxiety, depression, and intrusive thoughts. Agreement
      across raters was generally high, although interpretation of agreement levels was
      complex.

PMID- 12074379
TI  - AI and SAR approaches for predicting chemical carcinogenicity: survey and status
      report.
AB  - A wide variety of artificial intelligence (AI) and structure-activity
      relationship (SAR) approaches have been applied to tackling the general problem
      of predicting rodent chemical carcinogenicity. Given the diversity of chemical
      structures and mechanisms relative to this endpoint, the shared challenge of
      these approaches is to accurately delineate classes of active chemicals
      representing distinct biological and chemical mechanism domains, and within those
      classes determine the structural features and properties responsible for
      modulating activity. In the following discussion, we present a survey of AI and
      SAR approaches that have been applied to the prediction of rodent
      carcinogenicity, and discuss these in general terms and in the context of the
      results of two organized prediction exercises (PTE-1 and PTE-2) sponsored by the
      US National Cancer Institute/National Toxicology Program. Most models
      participating in these exercises were successful in identifying major structural
      alerting classes of active carcinogens, but failed in modeling the more subtle
      modifiers to activity within those classes. In addition, methods that
      incorporated mechanism-based reasoning or biological data along with structural
      information outperformed models limited to structural information exclusively.
      Finally, a few recent carcinogenicity-modeling efforts are presented illustrating
      progress in tackling some aspects of the carcinogenicity prediction problem. The
      first example, a QSAR model for predicting carcinogenic potency of aromatic
      amines, illustrates that success is possible within well-represented classes of
      carcinogens. From the second example, a newly developed FDA/OTR MultiCASE model
      for predicting the carcinogenicity of pharmaceuticals, we conclude that the
      definitions of biological activity and nature of chemicals in the training set
      are important determinants of the predictive success and specificity/sensitivity
      characteristics of a derived model.

PMID- 12074380
TI  - Bayesian analysis and inference from QSAR predictive model results.
AB  - QSAR models have been under development for decades but acceptance and
      utilization of model results have been slow, in part, because there is no widely
      accepted metric for assessing their reliability. We reapply a method commonly
      used in quantitative epidemiology and medical decision-making for evaluating the
      results of screening tests to assess reliability of a QSAR model. It quantifies
      the accuracy (expressed as sensitivity and specificity) of QSAR models as
      conditional probabilities of correct and incorrect classification of chemical
      characteristic, given a true characteristic. Using Bayes formula, these
      conditional probabilities are combined with prior information to generate a
      posterior distribution to determine the probability a specific chemical has a
      particular characteristic, given a model prediction. As an example, we apply this
      approach to evaluate the predictive reliability of a CATABOL model and base on it
      a "ready" and "not ready" biodegradability classification. Finally, we show how
      predictive capability of the model can be improved by sequential use of two
      models, the first one with high sensitivity and the second with high specificity.

PMID- 12074381
TI  - Androgen receptor binding affinity of pesticide "active" formulation ingredients.
      QSAR evaluation by COREPA method.
AB  - The COREPA approach for identifying the COmmon REactivity PAttern of biologically
      similar chemicals was employed to upgrade the recently derived affinity pattern
      for high androgen receptor (AR) binding affinity. The training set consisted of
      28 steroidal and nonsteroidal ligands whose AR binding affinity was determined in
      competitive binding assays (in terms of pKi). The interatomic distances between
      nucleophilic sites and their charges providing distinct and non-overlapping
      integral patterns for active and inactive chemicals were assumed that it was
      related with the endpoint, which was under study. These stereoelectronic
      characteristics were used to predict pKi values of pesticide "active" formulation
      ingredients in an attempt to identify chemicals with potential AR binding
      affinity.

PMID- 12074382
TI  - Membrane-contaminant interaction found by 3D force field calculations.
AB  - Enthalpies of contaminant transfer from water to a 1,2-Dilauroyl-DL-phosphatidyl
      ethanolamine (DLPE) membrane were calculated in order to study the suitability of
      3D force fields for the calculation of membrane-water partitioning constants
      (Kmw) and as potential descriptors for bio-concentration. A 3D DLPE membrane
      model was built in a MM+ force field using AM1 atomic charges. 3,5
      Dichlorobiphenyl (PCB14), 4,4'-dichlorobiphenyl (PCB15), 1,1,1-trichloro-2,2-bis
      (4-chlorophenyl)-ethane (PPDDT or p,p'-DDT) and 2-chloro-4-ethylamino-6
      isopropylamino-s-triazine (atrazine) were inserted into apolar and polar sites
      and their interaction energies with the membrane were calculated by geometrical
      optimization (GO). Energies of hydratation were subtracted from membrane
      contaminant interactions of selected sites. The resulting values for the
      enthalpies of transfer from water to the membrane were 4.7, -2.3, 11.5 and -9.2
      kcal/mol for PCB14, PCB15, PPDDT and atrazine, respectively. In contrast to
      PCB15, the value of PCB14 compared favorably with the experimental values of
      similar membranes. PCB14, PCB15 and PPDDT had their lowest energies in the apolar
      sites of the membrane, whereas atrazine tended to accumulate in the polar
      membrane-bulk water boundary site. Potential advantages and limitations of the
      approach were discussed.

PMID- 12074383
TI  - Mechanism based structure-activity relationships for skin sensitisation--the
      carbonyl group domain.
AB  - The biological activity of skin-sensitising chemicals is related to their ability
      to react either directly or after metabolic activity with appropriate skin
      proteins. For direct-acting electrophilic compounds, this ability can be modelled
      by the Relative Alkylation Index (RAI) by a combination of electrophilicity and
      hydrophobicity parameters. Several SARs based on this approach are reported. In
      this present work, electrophilicity parameters based on Taft substituent
      constants are used together with Leo and Hansch log P fragment values to
      calculate RAI values for hard electrophiles having a reactive carbonyl group.
      These are then applied to analysis of sensitisation data obtained in the murine
      Local Lymph Node Assay (LLNA) for two series of diketones as well as a homologous
      series of alpha, beta-unsaturated aldehydes. The sensitisation potentials of
      these reactive electrophiles show good correlations with the RAI. These findings
      re-affirm the view that physicochemical parameters are the key to eliciting the
      relationship between chemical structure and a toxic endpoint. They provide
      further evidence of the value of SAR studies in identifying mechanisms of
      sensitisation and aiding risk assessments without the need for extensive animal
      testing.

PMID- 12074384
TI  - QSAR's based on partial order ranking.
AB  - The development of Quantitative Structure Activity Relationships (QSAR's) often
      relies heavily on the application of statistical methods such as multi-linear
      regression (MLR) or principal component analysis/partial least square (PCA/PLS).
      Partial order ranking (POR), which from a mathematical point of view is based on
      elementary methods of Discrete Mathematics, appears as an attractive and
      operationally simple and more general alternative since the method does not
      require specific functional relationships between the single descriptors or the
      end-points. The POR method allows ranking of a series of compounds, based on
      selected descriptors characterizing their structural and/or electronic nature
      (model diagram). The ranking of the compounds based on their end-points
      (experimental ranking) can then be compared to the model diagram. If the model
      diagram resembles the experimental ranking of the end-points under investigation,
      other compounds, not being experimentally investigated, can be assigned a rank in
      the model and hereby obtain an identity based on the known compounds. The present
      study elucidates the applicability of POR as a simple tool for QSAR modeling.
      Based on illustrative examples the POR approach to QSAR modeling will be
      presented with special focus on the precision and the uncertainties of the
      method, which will be discussed in terms of the number of descriptors and
      compounds involved. The advantageous interplay between POR and PCA, the latter
      being applied in order to reduce a possible large number of descriptors into a
      limited number of latent descriptors will be discussed.

PMID- 12074386
TI  - Non-linear modeling of bioconcentration using partition coefficients for narcotic
      chemicals.
AB  - Bioconcentration factors (BCFs) have traditionally been used to describe the
      tendency of chemicals to concentrate in aquatic organisms. A reexamination of the
      log-log QSAR between the BCF and Kow for non-congener narcotic chemicals is
      presented on the basis of recommended data for fish. The model is extended to
      give a simple correlation between BCF and the toxicity of highly, moderately and
      weakly hydrophilic chemicals. For the first time, in this study an equation for
      calculating BCF was applied in a QSAR model for predicting the acute toxicity of
      chemicals to aquatic organisms.

PMID- 12074385
TI  - The importance of hydrophobicity and electrophilicity descriptors in
      mechanistically-based QSARs for toxicological endpoints.
AB  - Quantitative structure-activity relationship (QSAR) analysis of four
      toxicological data sets is described. The toxicological data include three data
      sets retrieved from the literature (the toxic and metabolic effects of 23
      aliphatic alcohols on the perfused rat liver; the toxicity of 21 pyridines to
      mice; the lethality of 55 halogenated hydrocarbons to the mould Aspergillus
      nidulans). In addition, the toxicity of 13 mono- and di-substituted nitrobenzenes
      in a 15 min assay using the alga Chlorella vulgaris was analysed. QSARs were
      developed successfully using descriptors to describe uptake in the organism (i.e.
      hydrophobicity as quantified by the logarithm of the octanol-water partition
      coefficient, log P) and reactivity at the site of action (i.e. electrophilicity
      as quantified by the energy of the lowest unoccupied molecular orbital, E(LUMO)).
      A further parameter describing molecular branching as also required to model the
      data for the aliphatic alcohols. The results demonstrate that mechanistically
      based QSARs can be developed for these diverse endpoints which are, in terms of
      statistical quality as good as, if not better, than QSARs based on less
      mechanistically interpretable descriptors.

PMID- 12074387
TI  - The components of the "critical quartet" log Kow values assessed by four
      commercial software packages.
AB  - Partition coefficient (log Kow) values of 103 compounds in four different solvent
      water systems (alkane-water, octanol-water, chloroform-water and propylene glycol
      dipelargonate (PGDP)-water--the "critical quartet") were published by Leahy et
      al. (1992). J. Chem. Soc. Perkin Trans. 2, pp. 723-731. They used the Abraham
      LSER (linear solvation energy relationship) descriptors to model the log Kow
      values in the four systems. The calculation of Abraham LSER descriptors has now
      been computerized in the ABSOLV program, and we have used ABSOLV, and three other
      commercial software packages (HYBOT-PLUS, Molecular Modeling Pro and QsarIS) that
      calculate descriptors of similar classes, to model partitioning in the four
      solvent-water systems. Stepwise regression selected broadly similar types of
      descriptor from each software package to model logKow values in each solvent
      water system. Overall, HYBOT-PLUS gave the best results. The rjle of the various
      classes of descriptor (size, polarity, polarizability, hydrogen bonding) in
      modeling partitioning in the four different solvent-water systems is discussed.

PMID- 12074388
TI  - Prediction of biodegradability from structure: imidazoles.
AB  - A project for the development of Structure-Activity Relationship for
      Biodegradation is presented. The aim of the project is to assemble sets of
      structural rules governing the potential microbial degradability of (classes of)
      chemicals. These rules will provide tools to take into account the biodegradation
      aspects of a product--and all precursors in the production process--early in the
      product development. The modeling concept is to take all experimental
      biodegradation data available and combine structural trends in the data with
      mechanistical information from degradation pathways. The rules that are derived
      should give insight into the possibility of biodegradation for specific classes
      of chemicals, thereby revealing why a compound is biodegradable or not. For the
      class of imidazole derivatives such rules are derived, and a model degradation
      mechanism is proposed in analogy to the urocanate-hydratase mechanism from
      histidine metabolism. The model is validated using 12 imidazole-compounds, which
      are all predicted correctly to be poorly biodegradable. It is demonstrated that
      both data analysis and information on enzymatic reaction mechanisms are necessary
      to yield valid Structure-Biodegradation Relationship.

PMID- 12074389
TI  - Modelling mutagenicity using properties calculated by computational chemistry.
AB  - The recent advances in combinatorial chemistry and high throughput screening
      technologies have led to an explosion in the numbers of possible therapeutic
      candidates being produced at the early stages of drug discovery. This rapid
      increase in the number of chemicals to be classified results in a greater need
      for alternative methods for the prediction of toxicity. Most QSAR models for
      mutagenicity have been constructed for congeneric series. The prediction
      requirements of the pharmaceutical industry, however, cover quite diverse
      chemical structures. This paper reports a study of mutagenicity data for a
      diverse set of 90 compounds. Good discriminant models have been built for this
      data set using properties calculated by the techniques of computational
      chemistry. Jack-knifed (leave one out) predictions for these models are of the
      order of 85%.

PMID- 12074390
TI  - An approach to the interpretation of backpropagation neural network models in
      QSAR studies.
AB  - An approach to the interpretation of backpropagation neural network models for
      quantitative structure-activity and structure-property relationships (QSAR/QSPR)
      studies is proposed. The method is based on analyzing the first and second
      moments of distribution of the values of the first and the second partial
      derivatives of neural network outputs with respect to inputs calculated at data
      points. The use of such statistics makes it possible not only to obtain actually
      the same characteristics as for the case of traditional "interpretable"
      statistical methods, such as the linear regression analysis, but also to reveal
      important additional information regarding the non-linear character of QSAR/QSPR
      relationships. The approach is illustrated by an example of interpreting a
      backpropagation neural network model for predicting position of the long-wave
      absorption band of cyane dyes.

PMID- 12074391
TI  - Uses and limitations of quantitative structure-activity relationships (QSARs) to
      categorize substances on the Canadian domestic substance list as persistent
      and/or bioaccumulative, and inherently toxic to non-human organisms.
AB  - Under sections 73 and 74 of the revised Canadian Environmental Protection Act
      (CEPA 1999), Environment Canada and Health Canada must "categorize" and "screen"
      about 23,000 substances on the Domestic Substances List (DSL) for persistence
      (P), bioaccumulation (B), and inherently toxic (iT) properties. Since
      experimental data for P, B and iT are only available for a few DSL substances, a
      workshop was held to address issues associated with the use of Quantitative
      Structure-Activity Relationships (QSARs) to categorize these substances. This
      paper describes the results of an 11-12 November 1999 International Workshop
      sponsored by Environment Canada to discuss potential uses and limitations of
      QSARs to categorize DSL substances as either persistent or bioaccumulative and iT
      to non-human organisms and to recommend future research needed to develop methods
      for predicting the P, B and iT of difficult-to-model substances.

PMID- 12074392
TI  - Probabilistic neural network modeling of the toxicity of chemicals to Tetrahymena
      pyriformis with molecular fragment descriptors.
AB  - We present the results of an investigation into the use of a probabilistic neural
      network (PNN) based methodology to model the 48-60-h ICG50 (inhibitory
      concentration for population growth) sublethal toxicity to the ciliate
      Tetrahymena pyriformis. The information fed into the neural network is solely
      based on simple molecular descriptors as can be derived from the chemical
      structure. In contrast to most other toxicological models, the octanol/water
      partition coefficient is not used as an input parameter and no rules of thumb, or
      other substance selection-criteria, are involved. The model was trained on a
      1,000 substances data set and validated using an 84 substances external test set.
      The associated analysis of errors confirms the excellent recognitive and
      predictive capabilities of the model.

PMID- 12074393
TI  - An integrated "4-phase" approach for setting endocrine disruption screening
      priorities--phase I and II predictions of estrogen receptor binding affinity.
AB  - Recent legislation mandates the US Environmental Protection Agency (EPA) to
      develop a screening and testing program for potential endocrine disrupting
      chemicals (EDCs), of which xenoestrogens figure prominently. Under the
      legislation, a large number of chemicals will undergo various in vitro and in
      vivo assays for their potential estrogenicity, as well as other hormonal
      activities. There is a crucial need for priority setting before this strategy can
      be effectively implemented. Here we report an integrated computational approach
      to priority setting using estrogen receptor (ER) binding as an example. This
      approach rationally integrates different predictive computational models into a
      "Four-Phase" scheme so that it can effectively identify potential estrogenic EDCs
      based on their predicted ER relative binding affinity (RBA). The system has been
      validated using an in-house ER binding assay dataset for 232 chemicals that was
      designed to have both broad structural diversity and a wide range of binding
      affinities. When applied to 58,000 chemicals identified by Walker et al. as
      candidates for endocrine disruption screening, some 9100 chemicals were predicted
      to bind to ER. Of these, only 3600 were expected to bind to ER at RBA values up
      to 100,000-fold less than that of 17beta-estradiol. The method ruled out 83% of
      the chemicals as non-binders with a very low rate of false negatives. We believe
      that the same integrated scheme will be equally applicable to endpoints of other
      endocrine disrupting mechanisms, e.g. androgen receptor binding.

PMID- 12074394
TI  - Decision support systems for chemical structure representation, reaction
      modeling, and spectra simulation.
AB  - The choice of an appropriate structure coding scheme is the secret to success in
      QSAR studies. Depending on the problem at hand, 2D or 3D descriptors have to be
      chosen; the consideration of electronic effects might be crucial, conformational
      flexibility has to be of special concern. Artificial neural networks, both with
      unsupervised and with supervised learning schemes, are powerful tools for
      establishing relationships between structure and physical, chemical, or
      biological properties. The EROS system for the simulation of chemical reactions
      is briefly presented and its application to the degradation of s-triazine
      herbicides is shown. It is further shown how the simulation of chemical reactions
      can be combined with the simulation of infrared spectra for the efficient
      identification of the structure of degradation products.

PMID- 12074395
TI  - Guidelines on bladder cancer.
AB  - OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for
      diagnosis, therapy and follow-up of bladder cancer patients were established.
      Criteria for recommendations were evidence based, and included aspects of cost
      effectiveness and clinical feasibility. METHOD: A systematic literature research
      using Medline Services was conducted. References were weighted by a panel of
      experts. RESULTS: TNM 1997 classification and WHO grading 1998 are recommended.
      Recommendations are developed for diagnosis for bladder cancer in general,
      treatment of superficial and infiltrative bladder cancer, and follow-up after
      different types of treatment modalities, such as intravesical instillations,
      radical cystectomy, urinary diversions, radiotherapy and chemotherapy.

PMID- 12074396
TI  - Androgen replacement therapy and prostate safety.
AB  - Progress in the understanding of the action of exogenous testosterone has
      diminished many of the concerns that existed regarding its safety. The major
      interest is now focused on the effects of androgen supplementation on the
      prostate gland. Many such concerns have been addressed but others remain to be
      fully elucidated. It is well established that hypogonadal men receiving adequate
      androgen therapy develop a prostate with a volume similar to what would be
      expected from their eugonadal counterparts. Androgen therapy results in modest
      elevations in the PSA and minor changes in flow parameters. Prostate cancer, on
      the other hand, remains the most prominent of the safety concerns. Although there
      is no evidence that normal levels of testosterone promote the development of
      cancer of the prostate, it is clear that the administration of testosterone
      enhances a pre-existing prostatic malignancy. Androgen supplementation studies
      have been, in most cases, of short duration and lacked a control cohort. The
      current evidence does not support the view that appropriate treatment of
      hypogonadal elderly men with androgens has a causal relationship with prostate
      cancer. Larger experience, however, is needed. The same criteria applies to the
      use of other hormones such as dehydrotestosterone, dehydroepiandrosterone
      follicle stimulating and growth hormone. A set of recommendations regarding
      androgen replacement therapy and prostate safety is proposed.

PMID- 12074397
TI  - Cryptorchidism, its impact on male fertility.

PMID- 12074398
TI  - The remnant urothelium after reconstructive bladder surgery.
AB  - The pathology of the remnant urinary tract in an increasing population of
      cystectomy patients with orthotopic and heterotopic bladder substitution due to
      primary bladder carcinoma, and its management is discussed. The incidence of
      urethral tumours in primary or recurrent bladder cancer in long-term studies is
      approximately 6% for male and 2% for female patients. Risk factors for urethral
      tumour occurrence are tumours at the bladder neck and recurrent multifocal
      tumours. CIS of the bladder not involving the bladder neck, and muscle invasive
      tumours with or without lymph node involvement are not significantly correlated
      with urethral cancer. Those patients at risk for urethral tumours need additional
      work-up (multiple urethral biopsies and/or urethral brushings, frozen section of
      the membranous urethra) before an orthotopic lower urinary tract reconstruction
      to the urethra should be considered. In a large series of male patients, the
      majority of patients with urethral tumours had a single conservative treatment
      session, and did not recur thereafter demonstrating the feasibility of a
      conservative approach for superficial urethral tumour recurrences in patients
      with an orthotopic neo-bladder to the urethra. The incidence of upper tract
      tumours following cystectomy and lower urinary tract reconstruction lies between
      2.4-17%. In a group of 258 patients with an orthotopic bladder substitution, we
      have seen an incidence of 3.5%. Tumour multifocality, carcinoma in situ in the
      bladder and/or distal ureter, locally advanced bladder tumour stage, and invasion
      of the intramural ureter were seen as risk factors in some series. A tendency for
      a higher incidence can be seen in those series with longer follow-up. The median
      time between cystectomy and diagnosis of upper tract tumours lies between 8 and
      69 months in most series. A longer observation period in larger numbers of
      patients with an orthotopic neo-bladder and longer survival rates in general
      after cystectomy may reveal an increase in the incidence of upper tract tumours
      over the next decade.

PMID- 12074399
TI  - Prevalence and correlates of erectile dysfunction in a population-based study in
      Belgium.
AB  - OBJECTIVES: This study aims to estimate the prevalence of erectile dysfunction
      (ED) in the male population of Belgium, and to study its correlation with
      education, the international prostate symptom scale (IPSS), sexual activity,
      depression, body mass index, alcohol, smoking, easiness to discuss ED with a
      doctor, current health index, physical activity, hypertension, diabetes,
      cardiovascular disease, professional status, residence and whether or not the
      respondent lives alone. METHODS: An age-stratified random sample of the male
      population aged 40-70 years of Ghent and Charleroi was interviewed in the home by
      a trained, experienced male nurse, using a structured interview that included the
      international index of erectile function (IIEF) and the IPSS. ED was classified
      by the subjects' self-reported confidence to achieve and maintain an erection.
      RESULTS: In total, 799 men were interviewed, with a participation rate of 38.0%.
      The overall age-adjusted prevalence of ED was 10.1% severe, 24.7% moderate, 26.6%
      mild, and 38.7% reported no ED. Age and the absence of sexual activity over the
      last 4 weeks were the strongest correlates of ED. Other strong correlates were
      four or more health complaints, depression, a high score for the IPSS and absence
      of physical activity. DISCUSSION: The prevalence of ED in Belgium is comparable
      with the results of other population-based studies for severe and moderate ED.
      Sexual inactivity over the last four weeks is a strong correlate of ED, and
      should make the clinician think of a possible problem of ED.

PMID- 12074400
TI  - Cycling and penile oxygen pressure: the type of saddle matters.
AB  - OBJECTIVES: Temporary genital numbness is a common side effect of long-distance
      cycling; cases of impotence have even been reported. Recent reports have shown
      that perineal compression leads to a decrease in penile blood flow. Reduced
      oxygen tension leads to penile fibrosis, which works counterproductively to the
      achievement of an erection. The shape of the bicycle saddle could be a factor
      affecting penile perfusion. The aim of this study is to find out the influence of
      different saddle designs on penile perfusion. MATERIAL AND METHODS: In 20 healthy
      athletic young men (mean age 26.8 years, range 21-31 years) without history of
      erectile dysfunction, transcutaneous oxygen pressure (PtcO2), which correlates
      with arterial and tissue PO2, was measured at the glans of the penis using a
      transcutaneous measurement device. All men were measured in a standing position
      before cycling, then during cycling in a seated position on a stationary bicycle.
      Four different bike saddle designs were used: (A) narrow heavily padded seat; (B)
      narrow seat with medium padding and a V-shaped groove in the saddle nose ("body
      geometry"); (C) wide unpadded leather seat; (D) women's special wide seat with
      medium padding and no saddle nose. RESULTS: During cycling in all seats a
      decrease in penile oxygen pressure could be observed, reflecting perineal
      compression. But the differences were unexpected: seat (A) mean PtcO2 11.8 mmHg,
      decrease in initial oxygen pressure 82.4%; seat (B) mean PtcO2 20.8 mmHg,
      decrease in initial oxygen pressure 72.4%; seat (C) mean PtcO2 25.3 mmHg,
      decrease in initial oxygen pressure 63.6%; seat (D) mean PtcO2 62.3 mmHg,
      decrease in initial oxygen pressure 20.3%. CONCLUSIONS: Cycling in a seated
      position leads to a compression of perineal arteries with a consequent
      significant decrease in penile perfusion. But, there are unexpected differences
      between different saddle types. It was possible to demonstrate that the most
      important factor in safeguarding penile perfusion is not the amount of padding,
      but rather a saddle width which prevents sufficiently the compression of the
      perineal arteries.

PMID- 12074401
TI  - Age dependent secretion of LH and ACTH in healthy men and patients with erectile
      dysfunction.
AB  - OBJECTIVES: Age dependent secretion of testicular and adrenal androgens was
      examined in healthy men and patients with erectile dysfunction (ED). METHODS: In
      95 healthy men (age 20-74 years) and 739 patients with ED, luteineizing hormone
      (LH, n = 739), adrenocorticotropic hormone (ACTH, n = 480) and the secretion
      products of testis and adrenal gland testosterone (T, n = 750), free testosterone
      (fT, n = 718), dehydroepiandrosteronesulfate (DHEAS, n = 598) and cortisol (n =
      538) were measured. RESULTS: In healthy men, LH was measured from 0.75-8.58
      mIU/ml and ACTH from 10.59-121.7 pg/ml. Statistically, age was not correlated to
      LH (P = 0.573) and ACTH (P = 0.833) in healthy men. The secretion products T (P <
      0.05), fT (P < 0.001), DHEAS (P < 0.001) and cortisol (P < 0.05) declined
      significantly with age in healthy persons. In patients with ED, a significant age
      dependent increase of LH (P < 0.05, n = 739), but not ACTH (P = 0.469, n = 480)
      was found. T (P < 0.001, n = 736), fT (P < 0.001, n = 718) and DHEAS (P < 0.001,
      n = 598), but not cortisol (P = 0.307, n = 538) declined in age dependent
      patients with ED. Age matching revealed a statistical significant elevation (P <
      0.05) only for LH (n = 659) in comparison to healthy men (n = 94), all other
      hormones were not different in both groups. CONCLUSION: An LH-increase in
      patients with erectile dysfunction underlines the importance of Leydig cell
      degeneration in this disease, but age dependent decline of T secretion was
      comparable to healthy men, demonstrating a working hypophyseal-testicular-axis.
      Indication of androgen replacement is therefore limited to selected cases.

PMID- 12074402
TI  - Assessment of clinical and pathologic characteristics predisposing to disease
      recurrence following radical prostatectomy in men with pathologically organ
      confined prostate cancer.
AB  - OBJECTIVE: To identify risk factors for biochemical failure after radical
      prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer
      (PCa). METHODS: Clinical and pathological characteristics of 331 consecutive men
      with pT2N0 PCa treated solely with RP were used in Cox proportional hazard models
      to identify independent predictors of prostate specific antigen (PSA) failure
      (PSA > or = 0.1 ng/ml). All pathologic specimens were step sectioned at 3 mm.
      RESULTS: Twelve patients (3.6%) failed at a median follow-up of 26 months (range
      0.2-99.6 months) and 120 men remained at risk 3 years after RP. In univariate Cox
      models PSA (P < 0.001), percentage of high-grade cancer (P < 0.001) total and
      high-grade cancer volume (P = 0.001 and P < 0.0001, respectively) and RP Gleason
      sum (P = 0.003) represented significant predictors of PSA failure. Clinical stage
      (P = 0.4), surgical margin status (P = 0.3), age (P = 0.2), and pathologic
      evidence of unilateral versus bilateral PCa (P = 0.6) failed to reveal
      significance. In receiver operator curve (ROC) analyses, high-grade cancer volume
      achieved highest outcome predictive accuracy (area under the curve (AUC 0.93)),
      which was not exceeded by Cox regression-based nomogram combining serum PSA, RP
      Gleason sum, margin status and pathologic evidence of unilateral versus bilateral
      PCa (AUC 091). Predictive accuracy of this multivariate nomogram was not enhanced
      by adding total cancer volume (AUC 0.93), high-grade cancer volume (AUC 0.90), or
      percentage of high-grade cancer (AUC 0.90). CONCLUSIONS: In pT2N0 PCa high-grade
      cancer volume appears to represent the most important pathologic factor for
      prediction of outcome following RP. However, similar predictive accuracy may be
      achieved by combining routinely available tumor characteristics.

PMID- 12074403
TI  - PSA-use in a Spanish industrial area.
AB  - OBJECTIVES: To document the extent of prostate-specific antigen (PSA)-testing in
      the general population at Getafe (Spain) outside our prostate cancer (PC)
      screening program, and to check its performance in terms of PC detection.
      METHODS: A total of 5371 PSA-test records (1997-1999) were reviewed and testing
      rates estimated per 1000 person-years. The extent of patient referral (men
      referred to our facilities) was calculated adjusting for PSA levels. To approach
      the performance of testing in the general population, our PC screening program
      acted as a standard for comparison. The probability of missing one PC in the
      general population was estimated in terms of number of men necessary to screen
      (NNS). Calculations were made adjusting for PSA levels. RESULTS: PSA-testing rate
      in the general population was 21.6/1000 person-years. In the age-group 55-69
      years, this rate was 86.8/1000 (152.6 in men >70 years). Referral rates were 67.9
      and 39.5% for men with PSA 4-10 and >10 ng/ml, respectively. Overall PC detection
      rate was 1.76%. Detection rates for PSA 4-10 and >10 ng/ml were 4.66 and 12.94%,
      respectively. When compared with the performance of the screening program, for
      every 17 men with a PSA in the range 4-10 ng/ml one cancer was missed (95%
      confidence interval (CI), 9-580). Similarly, one cancer was lost for every four
      men with a PSA >10 ng/ml (95% CI, 2-8). CONCLUSIONS: The extent of opportunistic
      testing in our setting is very high, particularly in the older age groups.
      Opportunistic screening renders PC detection rates lower than expected for every
      PSA level and cannot be encouraged.

PMID- 12074404
TI  - Gain in chromosome 8q correlates with early progression in hormonal treated
      prostate cancer.
AB  - OBJECTIVE: Development and especially hormone refractant progression of prostate
      cancer are incompletely understood. Clinical studies evaluating genetic
      aberrations of prior therapy biopsies in correlation with progression data in
      patients receiving hormone therapy for prostate cancer have not been performed
      until now. METHODS: After DNA isolation from histological sections of primary
      prostate cancer biopsies, comparative genomic hybridization (CGH) was performed
      according to standard protocols. Primary staging, clinical course and PSA levels
      of the patients were assessed. RESULTS: CGH was performed on 28 primary prostate
      cancer samples. After a mean follow-up of 36 months 11 (39%) of the patients
      showed progression of disease under hormonal treatment. In patients without and
      with progression we found the following results, respectively: losses of 6q
      (41/36%), 8p (41/45%), 16q (23/18%), 18q (30/9%), and gains of 8q (12/64%; P <
      0.0001) and 17 (47/26%). CONCLUSIONS: Gain of 8q is found predominantly in
      primary core biopsies of local advanced or metastasized prostate cancers. It
      shows in univariate analysis significant correlation with progression in hormone
      treated prostate cancer. This fact suggests that gain in 8q represents a marker
      of aggressiveness in prostate cancer.

PMID- 12074405
TI  - Clinical characteristics of prostate cancer in elderly Japanese patients 80 years
      of age or older.
AB  - OBJECTIVE: Prostate adenocarcinoma is predominantly a disease of elderly men.
      This study retrospectively examined prostate adenocarcinoma in Japanese patients
      80 years of age or older to determine the natural history and prognosis of this
      malignancy in the elderly population. METHODS: The medical records of 593
      patients were reviewed, with respect to age, histologic grade, clinical and
      pathological stage, treatment modality and clinical outcome. A variety of
      possible clinical factors were compared between patient groups > or = 80 and < 80
      years old. RESULTS: No significant difference in clinical stage, tumor grade, and
      performance status (PS) was found between two age groups of patients with
      prostate cancer. A significant stage migration between pre-PSA era and PSA era
      was found only in the group < 80 years old. In the series of stage D2 cancer
      patients, while there was no significant difference in cause-specific and
      progression-free survival rates between the two groups, the younger group < 80
      years old had a better marker response at 3 months from the start of endocrine
      therapy compared with the older group (P = 0.0048, chi2 analysis). CONCLUSION:
      These data suggest that patients > or = 80 years with prostate cancer present
      with similar histologic grade and disease stage as younger patients, although the
      younger group with stage D2 had a better marker response to endocrine therapy.

PMID- 12074406
TI  - Prediction of muscle invasion of bladder cancer by cystoscopy.
AB  - OBJECTIVES: Urologists make a decision on whether to indicate staging procedures
      for primary lesions of bladder cancer by findings of cystoscopy. However,
      cystoscopic findings for prediction of muscle-invasive bladder cancer have not
      been fully evaluated. METHODS: Two hundred seventy consecutive events of 165
      patients with bladder cancer were included in this study. Multivariate analysis
      by a logistic regression model was applied to analyze cystoscopic findings for
      prediction of muscle invasion of bladder cancer. RESULTS: Logistic regression
      analysis revealed that the size, stalk and configuration of the cancer were
      independent and significant factors that predict muscle invasion of bladder
      cancer. CONCLUSIONS: Cystoscopic findings of bladder cancer may predict muscle
      invasion. When invasion is suggested by cystoscopy, imaging studies may be
      necessary before TUR of the cancer as well as deep resection of it.

PMID- 12074407
TI  - p53 and ki67 expression as prognostic factors for cancer-related survival in
      stage T1 transitional cell bladder carcinoma.
AB  - OBJECTIVE: To determine prognostic factors for survival in bladder transitional
      cell carcinoma (TCC), and the prognostic value of p53 and ki67. MATERIAL AND
      METHODS: A study was made of patients with stage T1 primary bladder TCC (n =
      175). The immunohistochemical study was carried out using DO7 and MIB-1
      monoclonal antibodies, for p53 and ki67, respectively. Kaplan-Meier methodology
      was used for the survival analysis, and the log-rank test was applied in order to
      determine accumulated probability rates of survival. Moreover, Cox's multivariate
      regression analysis was also used to establish the variables associated with
      survival. Receiver operating characteristic (ROC) curves were also drawn, with
      the aim of determining the prognostic capacity of p53 and ki67. RESULTS: The
      average follow-up period was 7.3 years. Cancer-related survival rates at 5 and 10
      years were 89.51 and 80.68%, respectively. The increase in p53 and ki67
      expressions paralleled the histological grade, both markers showing significant
      inter-group differences (P = 0.0000). The variables which modified cancer-related
      survival significantly in the univariate analysis were the following: tumour
      multifocality, solid microscopic morphology, large cell nucleus and a high
      expression of p53 and ki67. Independent cancer-related survival variables were:
      age, tumour size of >3 cm, a solid microscopic growth pattern and expression of
      p53. CONCLUSIONS: The expression of p53, increase in age, tumour size of >3 cm
      and microscopic growth pattern are independent predictors for cancer-related
      survival. A positive correlation was observed, indicating that, the higher the
      expression of p53, the greater the probability of death.

PMID- 12074408
TI  - Prognostic factors in patients with renal cell carcinoma: retrospective analysis
      of 675 cases.
AB  - OBJECTIVES: To identify independent predictors of cause-specific survival in
      patients affected by renal cell carcinoma (RCC). MATERIAL AND METHODS: We
      evaluated retrospectively 675 patients who underwent in our department from 1976
      to 1999 radical nephrectomy for RCC. Pathological stage of the primary tumor
      (TNM, 1997) was pT1 in 326 cases (48%), pT2 in 133 (20%), pT3a in 66 (10%), pT3b
      in 138 (20%) and pT4 in 12 (2%). According to TNM classification (Union
      International Contre le Cancer (UICC), 1997) the pathological stage was I in 303
      cases (45%), II in 119 (18%), III in 150 (22%) and IV in 103 (15%). Histological
      grading was assigned according to Fuhrman's classification in only 333 cases: G1
      in 25%, G2 in 35%, G3 in 33% and G4 in 7%. RESULTS: Cause-specific survival was
      77% at 5 years, 69% at 10 years, 64% at 15 years and 57% at 20 years. Five and 10
      year cause-specific survival was, respectively 91.4 and 88.5% in pT1 tumors, 84.8
      and 72.7% in pT2, 57.4 and 35.6% in pT3a, 47.2 and 33.6% in pT3b-c, and 29.6% in
      pT4 (P < 0.0001). In relation to the pathological stage according to TNM
      classification, 5 and 10 year cause-specific survival was, respectively 94 and
      91.6% in stage I tumors, 89.7 and 78% in stage II, 63.4 and 46.4% in stage III
      and 28 and 16.3% in stage IV (P < 0.0001). In relation to the nuclear grade of
      the primary tumor 5 and 10 year cause-specific survival was, respectively 94 and
      88% in G1 tumors, 86 and 75% in G2, 59 and 40% in G3 and 31% in G4 (P < 0.0001).
      At multivariate analysis pathological stage of the primary tumor, lymph nodes
      involvement, presence of distant metastases at diagnosis and nuclear grading
      resulted all independent predictors of cause-specific survival in patients with
      RCC. CONCLUSION: Pathological stage of primary tumors, lymph nodes involvement,
      presence of distant metastases at diagnosis and nuclear grading according to
      Fuhrman resulted all independent predictors of cause-specific mortality in
      patients with RCC.

PMID- 12074409
TI  - Vitamin B12 and folate after 5-12 years of continent ileal urostomy (Kock
      reservoir) in children and adolescents.
AB  - OBJECTIVE: To assess B12 and folate deficiency after continent urinary diversion
      via a Kock continent urinary reservoir in children and adolescents. METHODS: Ten
      boys and 10 girls (10.8-18 years old at surgery) were operated with a Kock
      reservoir and followed for 5-12 years (mean 8.5). The follow-up period was
      divided into early (3 months-5 years, EFU) and late (5-12 years, LFU) follow-up.
      Patients were investigated for haemoglobin, serum iron, total iron binding
      capacity (TIBC), serum Vitamin B12, serum and blood folate, methylmalonic acid
      (MMA), homocystine and glomerular filtration rate. RESULTS: Two patients
      developed subnormal B12 values (median 107.5 pmol/l), one at the EFU, and the
      other at LFW. The B12 value decreased during the LFU compared to the EFU in nine
      patients, but it was still within the normal range. Two patients with renal
      impairment had elevated MMA with normal B12 values. Five patients had high values
      of homocystine with folate deficiency and/or B12 deficiency and renal impairment.
      Plasma folate mean value was normal during the whole follow-up. Blood folate was
      below normal in five patients at the EFU. Two of these five patients, in addition
      to three patients, had low values at the LFU. Three of four patients with
      remaining short terminal ileum (20-45 cm) had normal B12 values at both the EFU &
      LFU and one had low values at the LFU. Six patients had subnormal GFR at the LFU.
      CONCLUSIONS: To a similar degree as in adults, Vitamin B12, folate and iron
      deficiency can occur in children and adolescents after continent urinary
      diversion using an ileal segment. Therefore, Vitamin B12 and folate should be
      monitored regularly in these patients. Serum MMA and homocystine may offer
      increased detection of Vitamin B12 deficiency, especially in the patients with
      normal renal function. Vitamin B12 deficiency is neither correlated with the time
      elapsed since surgery, nor with the ileum length. Patients are usually
      asymptomatic, so patients with true B12 deficiency should be identified and
      placed on life-long Vitamin B12 therapy. An adequate synthetic folic acid as
      supplements or fortified food is recommended for patients with folate deficiency.

PMID- 12074410
TI  - Computerised assessment of maximum urinary flow: an efficient, consistent and
      valid approach.
AB  - OBJECTIVES: To evaluate the relative accuracy of a computerised method to
      quantitatively assess maximum urinary flow. METHODS: A total of 1147 uroflows
      were evaluated by the computerised method and by three experts from different
      European countries. The sample consisted of uroflows from the respective visits
      by a 20% sample of randomly chosen patients (n = 223) with lower urinary tract
      symptoms with participation in two clinical trials in which the efficacy and
      safety of Permixon was evaluated. The proportions of automated maximum flow
      values included in the 10% extended range of experts (and their 95% confidence
      intervals) were assessed, as well as the concordance coefficients between experts
      and the computerised method and the paired Student's t-test for the average
      differences between experts and computer. RESULTS: The rate of agreement between
      experts and computer varied between about 95 and 100% over factor levels for
      visit, type of machine and country. Concordance coefficients indicated good
      agreement between experts and the automated method. When looking at average
      differences between experts and the computer, the smallest differences were
      observed between experts 2, 3 and the computer (differences not statistically
      significant). Statistically significant average differences were observed between
      expert 1 and the other experts as well as between expert 1 and the computer.
      CONCLUSIONS: The computerised assessment decreases the fraction of variability of
      maximum urinary flow caused by artifacts as well as intra- and inter-expert
      variation. The computerised assessment of maximum urinary flow is an efficient,
      consistent and valid approach to quantitatively assess maximum urinary flow in
      clinical trials.

PMID- 12074411
TI  - Ultrasound assessment of detrusor muscle thickness in children with non
      neuropathic bladder/sphincter dysfunction.
AB  - OBJECTIVE: To measure detrusor muscle thickness in children with non-neuropathic
      bladder/sphincter dysfunction (NNBSD), and to evaluate the difference between
      children with various bladder dysfunctions and those with normal urodynamics.
      MATERIALS AND METHODS: In 139 children the urodynamic study was performed, and
      the detrusor of the anterior bladder wall was measured using high-frequency
      ultrasonography (US). Children were categorized into five groups, according to
      urodynamic findings. Differences in detrusor thickness between groups were tested
      by one-way ANOVA with post hoc Scheffe test. RESULTS: Forty-six children (33.1%)
      had normal urodynamics, and mean (+/-S.D.) detrusor thickness 1.3 +/- 0.5 mm
      (range 0.5-3.0). Fifty-two (37.4%) had urge syndrome, with detrusor thickness of
      2 +/- 0.7 mm (1.0-3.6). Thirty-three (23.7%) had dysfunctional voiding, with
      detrusor thickness of 2.6 +/- 0.5 mm (1.5-3.6). Four (2.9%) had lazy bladder,
      with detrusor thickness of 0.9 +/- 0.1 mm (0.8-1.0), and four had anatomical
      infravesical obstruction, with detrusor thickness of 4.4 +/- 0.3 mm (4-4.6). The
      mean detrusor thickness in all children with NNBSD was 2.2 +/- 0.7 mm (range 0.8
      3.6). Multiple comparisons showed significant difference between all groups,
      except between children with normal urodynamics and children with lazy bladder.
      CONCLUSION: There is statistically significant difference in mean detrusor
      thickness between children with normal urodynamics and children with NNBSD.
      However, due to the overlap of measured values, it is not possible to determine
      the cut-off value that could be used to distinguish children with and without
      NNBSD.

PMID- 12074412
TI  - Chylous ascites after radical nephrectomy and inferior vena cava thrombectomy.
      Successful conservative management with somatostatin analogue.
AB  - Postoperative chylous ascites is a rare complication of retroperitoneal surgery.
      The treatment of postoperative chylous ascites is primarily conservative,
      consisting of repeated paraceteses, medium chain triglyceride (MCT) diet, salt
      restriction, diuretics and bowel rest with total parenteral nutrition.
      Occasionally, chylous ascites may take a protracted course which may necessitate
      insertion of peritoneo-venous shunts or direct surgical lymphostasis. Recently,
      Somatostatin was shown to be highly effective in closure of refractory lymphatic
      fistulas. We present a case of refractory chylous ascites following radical
      nephrectomy with inferior vena caval thrombectomy that failed to respond to
      conventional conservative measures and resolved rapidly following the
      administration of Somatostatin.

PMID- 12074413
TI  - Ropivacaine and bupivacaine in obstetric analgesia.

PMID- 12074414
TI  - Allergic reactions occurring during anaesthesia.
AB  - Anaphylactic reactions to anaesthetic and associated agents used during the
      perioperative period have been reported with increasing frequency in most
      developed countries. Any drug administered in the perioperative period can
      potentially produce life-threatening immune-mediated anaphylaxis. Most published
      reports on the incidence of anaphylaxis come from France, Australia, the UK and
      New Zealand. These reflect an active policy of systematic clinical and/or
      laboratory investigation of suspected immune-mediated reactions. The estimated
      incidence of anaphylaxis ranges from 1:10,000 to 1:20,000. Muscle relaxants
      (69.1%) and latex (12.1%) were the most frequently involved drugs according to
      the most recent French epidemiological survey. Clinical symptoms do not afford an
      easy distinction between immune-mediated anaphylactic reactions and anaphylactoid
      reactions resulting from direct non-specific histamine release. Moreover, when
      restricted to a single clinical symptom, anaphylaxis can easily be misdiagnosed.
      Pre- and postoperative investigation must be performed to confirm the nature of
      the reaction, the responsibility of the suspected drugs and to provide precise
      recommendations for future anaesthetic procedures. These include plasma
      histamine, tryptase and specific IgE concentration determination at the time of
      the reaction and at skin tests 6 weeks later. In addition, since no specific
      treatment has been shown reliably to prevent the occurrence of anaphylaxis,
      allergy assessment must be performed in all high-risk patients. Treatment of
      anaphylaxis is aimed at interrupting contact with the responsible antigen,
      inhibiting mediator production and release, and modulating the effects of
      released mediators. It must be initiated as quickly as possible and relies on
      widely accepted principles. Finally, the need for proper epidemiological studies
      and the relative complexity of allergy investigation should be underscored. They
      represent an incentive for further development of allergo-anaesthesiology
      clinical networks to provide expert advice for anaesthetists and allergologists.

PMID- 12074415
TI  - Comparison of bupivacaine 0.2% and ropivacaine 0.2% combined with fentanyl for
      epidural analgesia during labour.
AB  - BACKGROUND AND OBJECTIVE: Recent clinical studies comparing ropivacaine 0.25%
      with bupivacaine 0.25% reported not only comparable analgesia, but also
      comparable motor block for epidural analgesia during labour. An opioid can be
      combined with local anaesthetic to reduce the incidence of side-effects and to
      improve analgesia for the relief of labour pain. The purpose of the study was to
      evaluate the effects of epidural bupivacaine 0.2% compared with ropivacaine 0.2%
      combined with fentanyl for the initiation and maintenance of analgesia during
      labour and delivery. METHODS: Sixty labouring nulliparous women were randomly
      allocated to receive either bupivacaine 0.2% with fentanyl 2 microg mL(-1) (B/F),
      or ropivacaine 0.2% with fentanyl 2 microg mL(-1) (R/F). For the initiation of
      epidural analgesia, 8 mL of the study solution was administered. Supplemental
      analgesia was obtained with 4 mL of the study solution according to parturients'
      needs when their pain was > or = 4 on a visual analogue scale. Analgesia, hourly
      local anaesthetic use, motor block, patient satisfaction and side-effects between
      groups were evaluated during labour and at delivery. RESULTS: Sixty patients were
      enrolled and 53 completed the study. No differences in verbal pain scores, hourly
      local anaesthetic use or patient satisfaction between groups were observed.
      However, motor block was observed in 10 patients in the B/F group whereas only
      two patients had motor block in the R/F group (P < 0.05). The incidence of
      instrumental delivery was also higher in the B/F group than in the R/F group (P <
      0.05). CONCLUSIONS: The results suggest that epidural bupivacaine 0.2% and
      ropivacaine 0.2% combined with fentanyl produced equivalent analgesia for pain
      relief during labour and delivery. It is concluded that ropivacaine 0.2% combined
      with fentanyl 2 microg mL(-1) provided effective analgesia with significantly
      less motor block and need for an instrumental delivery than a
      bupivacaine/fentanyl combination at the same concentrations during labour and
      delivery.

PMID- 12074416
TI  - Fentanyl added to bupivacaine 0.05% or ropivacaine 0.05% in patient-controlled
      epidural analgesia in labour.
AB  - BACKGROUND AND OBJECTIVE: Epidural analgesia is the most effective method for
      pain relief during labour. The aim was to elucidate the efficacy of ropivacaine
      0.05% and bupivacaine 0.05%, which were both combined with fentanyl 0.00015% to
      provide analgesia in labour. METHODS: Forty nulliparous females were enrolled
      into the study. After insertion of an epidural catheter, patients were randomly
      assigned into two groups. Once the os uteri had dilated to 4-5 cm, a bolus of
      bupivacaine 0.125% 10mL + fentanyl 50 microg (1 mL) in Group 1 patients, and
      ropivacaine 0.125% 10mL + fentanyl 50 microg (1 mL) in Group 2 patients was
      administered via the epidural catheter. Then, patient-controlled epidural
      analgesia was started with a basal infusion of bupivacaine 0.05% 10 mLh(-1) +
      fentanyl 0.00015% 1.5 pgmL(-1) in Group 1, and ropivacaine 0.05% + fentanyl 1.5
      microgmL(-1) in Group 2. When needed, a 10 mL bolus infusion could be given and
      the lockout time was 20 min. Maternal and fetal haemodynamic variables were
      monitored before induction and subsequently at 5 min intervals. Using a visual
      analogue scale assessed the degree of pain. RESULTS: Maternal haemodynamic
      variables and Apgar scores were not different between the two groups. The second
      stage of the labour was shorter in Group 2 (P < 0.01). There were no significant
      differences in patients' assessment of motor block or mode of delivery between
      groups. CONCLUSIONS: An epidural infusion (10 mLh(-1)) of bupivacaine 0.05% or
      ropivacaine 0.05% together with fentanyl 1.5 microg mL(-1) provided good and safe
      analgesia during labour.

PMID- 12074418
TI  - Use of sevoflurane during cardiopulmonary bypass decreases incidence of
      awareness.
AB  - BACKGROUND AND OBJECTIVE: The role of sevoflurane has not been studied in
      relation to awareness during anaesthesia. We observed the effect of sevoflurane
      on the incidence of awareness during cardiopulmonary bypass for open-heart
      surgery. METHODS: Fifty-nine patients of age >17 yr undergoing open-heart surgery
      with cardiopulmonary bypass were randomly assigned to two groups. In both groups,
      induction was with etomidate, dehydrobenzperidol and fentanyl; anaesthesia was
      maintained with sevoflurane, fentanyl and N20; vecuronium was used for muscular
      paralysis. Group 1 (30 patients) received dehydrobenzperidol and fentanyl during
      cardiopulmonary bypass; Group 2 (29 patients) received sevoflurane and fentanyl.
      Patients were given different auditory inputs during different phases of surgery.
      All patients were interviewed with standard questions 8 and 24 h postoperatively
      for evidence of explicit awareness. RESULTS: Five patients in the
      dehydrobenzperidol group gave a history of awareness (16.67%) as opposed to none
      in the sevoflurane group. The difference in the incidences of awareness was
      significant (P < 0.05), but no differences were found between the interviews
      conducted at 8 and 24 h. Sevoflurane and opioid combination reduced the incidence
      of awareness in open-heart surgery.

PMID- 12074417
TI  - Effect of VIMA with sevoflurane versus TIVA with propofol or midazolam-sufentanil
      on the cytokine response during CABG surgery.
AB  - BACKGROUND AND OBJECTIVE: Cardiac surgery with cardiopulmonary bypass triggers an
      inflammatory response involving pro-inflammatory cytokines such as tumour
      necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8).
      We investigated whether different anaesthetic techniques alter the pro
      inflammatory cytokine response to cardiac surgery. METHODS: Thirty patients
      scheduled for elective coronary artery bypass grafting (CABG) surgery were
      randomized into three groups of 10 patients. They received either volatile
      inhalation induction and maintenance (Group 1) or total intravenous anaesthesia
      with propofol and a minimal dose sufentanil (Group 2) or a moderate dose
      midazolam-sufentanil (Group 3). The effect of the different anaesthetic
      techniques on plasma levels of TNF-alpha, IL-6 and IL-8 were examined during and
      after anaesthesia. RESULTS: Concentrations of TNF-alpha, and IL-8 were comparable
      in the three groups throughout all measurements. Before the start of
      cardiopulmonary bypass, IL-6 was significantly higher in Group 1 than in Group 2
      (P = 0.009) or Group 3 (P = 0.030), but there were no differences between groups
      after cardiopulmonary bypass or postoperatively. In the three groups there was a
      positive correlation between aortic clamping time and serum concentrations of IL
      6 (r = 0.54) and IL-8 (r = 0.62). Length of stay in intensive care was correlated
      with high levels of TNF-alpha (r = 0.78). CONCLUSIONS: Albeit there is difference
      between the volatile induction and maintenance of the anaesthesia method and the
      total intravenous anaesthesia technique on the pro-inflammatory cytokine response
      to surgical stimulation before starting of cardiopulmonary bypass, neither
      technique can modify the pro-inflammatory cytokine response to ischaemia
      reperfusion or extracorporeal circulation.

PMID- 12074419
TI  - Monitoring intravascular volumes for postoperative volume therapy.
AB  - BACKGROUND AND OBJECTIVE: The feasibility of monitoring measured intravascular
      volumes and the cardiac filling pressures were compared to reflect the optimal
      volume status of postoperative patients. METHODS: In a prospective clinical
      study, 14 hypovolaemic adult patients were included after cardiac surgery. All
      patients received 1,000 mL hydroxyethyl starch after meeting the authors'
      criteria for hypovolaemia. Pressures were measured by use of a pulmonary artery
      catheter and volumes were determined by double-indicator dilution technique.
      RESULTS: Stroke volume index (SVI), central venous pressure (CVP), pulmonary
      artery occlusion pressure (PAOP), intrathoracic blood volume index (ITBVI) and
      total circulating blood volume (TBVIcirc) increased
      significantlyaftervolumeloading(30.7 +/- 9.8 to 41.7 +/- 9.6 mLm(-2), 4.9 +/- 1.7
      to 9.1 +/- 2.3mmHg, 6.6 +/- 1.3 to 10.6 +/- 1.9 mmHg, 858 +/- 255 to 965 +/- 163
      mLm(-2), and 1,806 +/- 502 to 2,110 +/- 537 mLm(-2), respectively). During the
      subsequent 1 h steady-state period, CVP and PAOP decreased significantly (9.1 +/-
      2.2 to 7.4 +/- 2.2 mmHg and 10.6 +/- 1.9 to 9.2 +/- 2.0 mmHg, respectively),
      whereas SVI and intravascular volumes remained unchanged. The changes of CVP and
      PAOP did not correlate with changes in stroke volume during volume loading (r2 =
      0.06 and 0.03, respectively) and during steady-state (r2 = 0.17 and 0.00
      respectively). On the other hand, a significant correlation was found between
      changes of the intrathoracic blood volume and changes in stroke volume during the
      volume loading (r2 = 0.67) and also during the steady-state phase (r2 = 0.83).
      CONCLUSIONS: Intrathoracic blood volume reflects more accurately the preload
      dependency of cardiac output in postoperative patients than left/right-sided
      cardiac filling pressures.

PMID- 12074420
TI  - Stability of a sufentanil-ropivacaine mixture in a glass and a PVC reservoir.
AB  - BACKGROUND AND OBJECTIVE: Drug mixtures containing sufentanil may be unstable
      owing to absorption into the drug reservoirs of patient-controlled epidural
      analgesia systems that contain polyvinylchloride. The stability of sufentanil in
      a mixture of ropivacaine 0.2% in a 750 mL reservoir was therefore investigated.
      METHODS: During simulated epidural infusions of 5 mLh(-1) at 25 degrees C,
      sufentanil concentrations were measured for 96 h. Samples were taken from the
      reservoir and from the end of the epidural catheter under the following
      conditions: into glass or polyvinylchloride reservoirs containing ropivacaine
      0.2% with sufentanil 1, 0.75 or 0.5 microg mL(-1); and into polyvinylchloride
      reservoirs with ropivacaine 0.2% and sufentanil 1 microg mL(-1) which were stored
      for 4 weeks at 8 degrees C. RESULTS: The different solutions remained stable over
      the observation period of 96 h. Using the same solutions, independent samples'
      ANOVA showed no difference in the sufentanil concentrations between the glass and
      polyvinylchloride reservoirs, or between the polyvinylchloride reservoirs when
      stored for 4 weeks. Correlations between the concentrations at the different
      measurement times were extremely high for the reservoir (r(min) = 0.98, r(max) =
      1.00) and the catheter end (rmin = 0.86, r(max) = 1.00). CONCLUSIONS: Sufentanil
      citrate at 0.5-1.0 microg mL(-1) in an admixture of ropivacaine 0.29 for 5 days,
      which is the usual period for postoperative epidural analgesia, remains stable in
      a polyvinylchloride reservoir. There is no change in the drug concentration even
      if the reservoir is stored for 4 weeks at 8 degrees C.

PMID- 12074421
TI  - Use of the intubating laryngeal mask airway in a case of ankylosing spondylitis
      for coronary artery bypass grafting.
AB  - The intubating laryngeal mask airway is a modification of the conventional
      laryngeal mask and is used as a tool for difficult intubation. It can be inserted
      without placing the head and neck in the Magill position and has been used
      successfully in cervical spine injuries. Reported is a case of successful
      insertion of the intubating laryngeal mask and subsequent intubation through it
      in a patient with ankylosing spondylitis with cervical involvement resulting in a
      fixed flexion deformity who underwent coronary artery bypass grafting.

PMID- 12074422
TI  - Investigating the usefulness of the laryngeal tube in spontaneously breathing
      patients.

PMID- 12074423
TI  - Efficacy of the laryngeal tube.

PMID- 12074424
TI  - Fibreoptic control of the laryngeal tube position.

PMID- 12074426
TI  - Visibility: science and regulation.
AB  - The 1999 Regional Haze Rule provides a context for this review of visibility, the
      science that describes it, and the use of that science in regulatory guidance.
      The scientific basis for the 1999 regulation is adequate. The deciview metric
      that tracks progress is an imperfect but objective measure of what people see
      near the prevailing visual range. The definition of natural visibility conditions
      is adequate for current planning, but it will need to be refined as visibility
      improves. Emissions from other countries will set achievable levels above those
      produced by natural sources. Some natural events, notably dust storms and
      wildfires, are episodic and cannot be represented by annual average background
      values or emission estimates. Sulfur dioxide (SO2) emission reductions correspond
      with lower sulfate (SO4(2-)) concentrations and visibility improvements in the
      regions where these have occurred. Non-road emissions have been growing more
      rapidly than emissions from other sources, which have remained stable or
      decreased since 1970. Simpler models representing transport, limiting precursor
      pollutants, and gas-to-particle equilibrium should be used to understand where
      and when emission reductions will be effective, rather than large complex models
      that have insufficient input and validation measurements. Examples of model-based
      source attribution show large differences among estimates from various modeling
      systems and with ambient measurements.

PMID- 12074425
TI  - Bupivacaine pharmacokinetics and motor blockade following epidural administration
      of the bupivacaine-sulphobutylether 7-beta-cyclodextrin complex in sheep.

PMID- 12074427
TI  - The wind-frequency allocation method on discharge loading of function zones.
AB  - This paper introduces a new allocation method on discharge loading of each
      function zone in a total emission control region. The wind frequency, the
      position of each district, and the pollutant's influence area were taken into
      account in this new method. The concept of "average downwind distance" was
      brought forward in this paper. The method here is more reasonable than the
      original method of area distribution, which was proposed by the "A-value" method
      in regulation of total emissions in China, by means of the simulation of annual
      average concentration in the total emission control region.

PMID- 12074428
TI  - Sector analysis of pH values in the northeastern region of Puerto Rico.
AB  - Acid rain precipitation has become a major environmental concern. Many long-range
      projects in the United States and Europe are devoted to the problems associated
      with acid rain pollution. In Puerto Rico, there has been no formal study on acid
      rain. The rainfall pH values and the air-mass trajectory of the northeastern part
      of the island of Puerto Rico on the surface were analyzed from January 1998 to
      December 2000. The air-mass trajectory was classified in five different sectors,
      according to where it originates. The mean pH value measured during that period
      showed a tendency toward acidity. The 80% of the air-mass trajectory that arrived
      at the station occurred in Sector I, with a pH value of 4.30. The lowest pH value
      measured was 4.16, and it occurred in Sector V, where the air mass originates in
      the northwest part of the island.

PMID- 12074429
TI  - Stabilization of APC residues from waste incineration with ferrous sulfate on a
      semi-industrial scale.
AB  - A stabilization method for air pollution control (APC) residues from municipal
      solid waste incineration (MSWI) involving mixing of the residue with water and
      FeSO4 has been demonstrated on a semi-industrial scale on three types of APC
      residues: a semidry (SD) APC residue, a fly ash (FA), and an FA mixed with sludge
      (FAS) from a wet flue gas cleaning system. The process was performed in batches
      of 165-175 kg residue. It generates a wastewater that is highly saline but has a
      low content of heavy metals such as Cd, Cr, and Pb. The stabilized and raw
      residues have been subject to a range of leaching tests: the batch leaching test,
      the pH-static leaching test, the availability test, and the column test. These
      tests showed that the stabilized residues have remarkably improved leaching
      properties, especially with respect to Pb but also with respect to Cd, Cu, and
      Zn. The release of Pb was reduced by a factor of 250-36,000.

PMID- 12074430
TI  - Sources of atmospheric carbonaceous particulate matter in Pittsburgh,
      Pennsylvania.
AB  - The organic carbon (OC)/elemental carbon (EC) tracer method is applied to the
      Pittsburgh, PA, area to estimate the contribution of secondary organic aerosol
      (SOA) to the monthly average concentration of organic particulate matter (PM)
      during 1995. An emissions inventory is constructed for the primary emissions of
      OC and EC in the area of interest. The ratio of primary emissions of OC to those
      of EC ranges between 2.4 in the winter months and 1.0 in the summer months. A
      mass balance model and ambient measurements were used to assess the accuracy of
      the emissions inventory. It is estimated to be accurate to within 50%. The
      results from this analysis show a strong monthly dependence of the SOA
      contribution to the total organic PM concentration, varying from near zero during
      winter months to as much as 50% of the total OC concentration in the summer.

PMID- 12074431
TI  - Neurotrauma: the role of CT angiogram.
AB  - Cerebrovascular injuries can occur in blunt or penetrating head and neck trauma.
      A high index of suspicion based on mechanism of injury and clinical assessment
      warrants screening for intracranial and extracranial vascular lesions.
      Conventional angiogram has been and remains the gold standard for diagnosis of
      these injuries, but computerized tomography angiography offers a fast,
      noninvasive method of imaging for neurotrauma patients. Advantages and
      disadvantages of each modality are discussed.

PMID- 12074432
TI  - New techniques in cerebral imaging.
AB  - This article presents a review of the current techniques in Computed Tomography
      (CT) and Magnetic Resonance Imaging (MRI) that enhance the usefulness of these
      tests for the diagnosis of cerebral disease. We were able to analyze concepts and
      definitions and give a comparative description for each test studied including
      Multidetector/Perfusion CT, Xenon CT, CT-Angiogram, MRI-Perfusion, MRI-Diffusion,
      MRI-Spectroscopy, MRI CSF Flow, Functional MRI studies and Cerebral Angiography.

PMID- 12074433
TI  - Stroke trials: what have we learned?
AB  - We reviewed the recent, major, therapeutic trials of intravenous thrombolytic
      therapy and ancrod for ischemic stroke. Randomized, controlled studies of acute
      ischemic stroke treatment were reviewed. Several post-FDA approval intravenous
      tPA studies were reviewed to understand the experience of this medication in
      practice. STAT trial was the major study using ancrod. Of multiple intravenous
      thrombolytic studies, the NINDS study of intravenous tPA was the only study to
      demonstrate a significantly higher percentage of patients with complete recovery
      or minimal deficit at three months. Studies in communities utilizing intravenous
      tPA for stroke illustrate the need for close adherence to the NINDS study
      protocol or else the risk of tPA use may exceed the benefits.

PMID- 12074434
TI  - In less than a lifetime, the treatment of neurovascular disease has progressed at
      a dizzying pace.

PMID- 12074435
TI  - The physics of endoluminal stenting in the treatment of cerebrovascular
      aneurysms.
AB  - Endovascular stenting of aneurysms offers potential advantages over surgical
      clipping. Stenting is minimally invasive, and with the implementation of rapidly
      developing micro and nano technologies, it will in the future be possible to
      deploy stents in more remote locations of the cerebrovasculature. The key
      advantage of stenting is that in addition to impeding flow into the aneurysm, it
      provides the parent artery with a scaffold over which the artery can remodel.
      However, for a stent to be effective in this goal, it must be tailored to the
      local hemodynamics at the aneurysm site. This paper is a review of the
      qualitative and quantitative in vitro and in vivo experimentation as well as
      computer simulations that have been performed to elucidate the effects of various
      stent design parameters and the prevailing parent vessel hemodynamics on intra
      aneurysmal flow patterns. Our results in numerous studies have shown that
      stenting substantially alters intra-aneurysmal flow. Furthermore, it is
      demonstrated that techniques have been developed in order to assess the efficacy
      of the stent in promoting intra-aneurysmal flow stagnation, thus creating the
      potential to optimize the device design for the treatment of intracranial
      aneurysms.

PMID- 12074436
TI  - Developments in endovascular therapy for acute ischemic stroke.
AB  - Treatment for acute ischemic stroke has for years been frustrated by lack of
      efficacy. Despite a plethora of seemingly promising treatments from animal
      research, clinical application never came to fruition. Experience seems to
      indicate that the only truly effective treatment is the rapid restoration of
      perfusion to ischemic tissue prior to frank infarction. Unfortunately, every
      agent designed to achieve this goal met with the same ironic limitation; the
      ability to dissolve clot was coupled with the risk of causing intracerebral
      hemorrhage. Accordingly, stroke was addressed primarily through modification of
      risk factors and rehabilitation of the neurological sequelae. However, following
      the randomized trial of intravenous tissue-type plasminogen activator (t-PA)
      sponsored by the National Institutes of Neurological Disorders and Stroke (NINDS)
      in 1995, the first proven effective therapy for acute stroke became available.
      The door was finally open to emergency treatment of stroke in the acute phase.
      Moreover, the positive results of the NINDS trial appear to be independent of
      age. Nevertheless, intravenous thrombolysis remains ineffective in the majority
      of patients treated and is withheld from an even larger population because of
      presentation outside of the 3-hour therapeutic window. As a result, effective
      therapy is not available for most patients presenting with acute stroke. Recent
      advancements in the evaluation and treatment of acute ischemic stroke, including
      intra-arterial thrombolysis, mechanical thrombolysis, and combination therapies,
      hold significant promise for a larger proportion of patients. New imaging
      technology may also improve our ability to identify patients with viable brain
      tissue who may derive the greatest benefit from these therapies.

PMID- 12074437
TI  - Critical care issues in stroke and subarachnoid hemorrhage.
AB  - The outcomes of devastating neurological emergencies such as stroke and
      subarachnoid hemorrhage may be measurably improved by timely treatment in a
      neurointensive care unit (NICU). Optimal care requires a multidisciplinary
      approach, with attention to a wide range of treatment issues. This review
      examines the key therapeutic concerns in the NICU management of acute ischemic
      and hemorrhagic stroke and subarachnoid hemorrhage, including mechanical
      ventilation, blood pressure management, cardiac monitoring, intracranial pressure
      assessment, vasospasm, seizures, sedation, fluids, electrolytes, and nutrition.
      The discussion of mechanical ventilation includes rapid sequence induction and
      intubation, indication for intubation and extubation, and prognostic factors in
      mechanical ventilation. Differing blood pressure management concerns in
      hemorrhagic and ischemic events are discussed, and specific target blood
      pressures and pharmacologic interventions are reviewed. The discussion of cardiac
      monitoring includes concurrent stroke and cardiac ischemia and arrhythmias,
      cardiac imaging, anticoagulation, and vasopressor therapy. The importance,
      monitoring and management of cerebral blood flow and intracranial pressure (ICP)
      are discussed, and strategies for treatment of elevated ICP are outlined in
      detail. The discussion of vasospasm includes evaluation, prophylaxis, and
      treatment with medications, hypervolemic hemodilution, and angioplasty.
      Management of seizure and status epilepticus in stroke and subarachnoid
      hemorrhage are reviewed and current algorithms are presented. The management of
      fluids, electrolytes and enteral nutrition are also reviewed.

PMID- 12074438
TI  - Outcome following intracerebral hemorrhage and subarachnoid hemorrhage.
AB  - Intracerebral hemorrhage and subarachnoid hemorrhage account for almost 20% of
      all stroke cases. Both forms of stroke are associated with a high morbidity and
      mortality rate. The incidence of intracerebral hemorrhage increases with the age
      and certain ethnical groups are more affected. Subarachnoid hemorrhage tends to
      occur in a much younger population than other types of strokes. Outcome
      predictors for intracerebral and subarachnoid hemorrhage have been extensively
      discussed in the literature. Based on the current literature, we review the
      morbidity and mortality rates and predictors of outcome for these two life
      threatening diseases. Initial Glasgow Coma Scale (GCS) score, hematoma volume,
      and presence of ventricular blood are the most prominent predictors of outcome
      following intracerebral hemorrhage. Age and initial severity of neurologic
      deficits on presentation, measured by GCS, Hunt and Hess Scale or the World
      Federation of Neurological Surgeons Scale, are the most important predictors of
      outcome following subarachnoid hemorrhage.

PMID- 12074439
TI  - Carotid artery stenting for high-risk patients.
AB  - Carotid artery stenting is being increasingly considered as a treatment option
      for high-risk patients with internal carotid artery atherosclerosis or
      vasculopathies. Since carotid endarterectomy is a procedure with a longer track
      record, some clinicians consider stenting to be appropriate only in high-risk
      conditions such as patients with severe medical comorbidities, recurrent stenosis
      following previous endarterectomy, or radiation-induced stenosis. The application
      of stenting in these areas is discussed, as well as the potential role for
      stenting in patients with acute ischemic stroke.

PMID- 12074440
TI  - Carotid endarterectomy in high risk patients.
AB  - We elected to compare the clinical outcomes of carotid endarterectomy (CEA)
      patients who were thought to be at increased risk for peri-operative
      complications because of advanced age (> 79 years), medical comorbidities and
      contralateral internal carotid artery occlusion to patients without these risk
      factors. A prospective series of 875 CEAs done using regional anesthesia were
      analyzed. All patients were operated upon under the direction of one neurosurgeon
      (REH). Clinical outcomes measures evaluated were any stroke, death or myocardial
      infarction within 30 days of operation. All patients were followed to a clinical
      endpoint and/or six weeks post-operatively. The incidence of adverse clinical
      outcomes in the suspected high risk patients was compared to the incidence in the
      entire series using contingency table analysis (Chi-square and Fisher's exact
      test). Twenty strokes (2.3%), four myocardial infarctions (0.5%) and three deaths
      (0.3%) occurred within 30 days of CEA. None of the suspected risk factors was
      associated with a significantly (p < 0.05) increased risk of peri-operative
      morbidity or mortality. CEA using regional anesthesia can be performed in
      patients with advanced age, diabetes mellitus, atherosclerotic coronary vascular
      disease and contralateral ICA occlusion with acceptably low peri-operative
      morbidity.

PMID- 12074441
TI  - Training the cerebrovascular surgeon for the 21st century.

PMID- 12074443
TI  - Future of extracranial-intracranial bypass.
AB  - Total occlusion of internal carotid artery in the cervical region is an end
      result of progressive occlusive vascular disease. A small proportion of these
      patients will have symptoms of cerebral ischemia due to cerebral hypoperfusion in
      a delayed fashion. Identification of those individuals who are at risk of
      developing symptoms and prophylactically treating with a revascularization
      procedure will prevent such catastrophic events. With the co-operative study for
      bypass not supporting the bypass procedure and trial being questioned for its
      design and conclusions, a new trial of extracranial-intracranial bypass, The
      Carotid Occlusion Surgery Study, using the currently available technology will be
      undertaken to verify that the bypass will decrease the future stroke rate by at
      least 40% in patients with total carotid occlusion. A subset of patients with
      skull base pathology including tumors and aneurysms who may have to undergo
      carotid sacrifice as part of the surgical procedure are at risk of peri-operative
      and delayed stroke. Identification of these patients at risk by pre-operative
      tests may allow performance of extracranial-intracranial bypass prior to
      undertaking complex skull base procedures. The new imaging technology will guide
      management of these patients at risk and help identify patients who may need a
      bypass procedure.

PMID- 12074442
TI  - Endovascular aneurysm treatment: a proven therapy.
AB  - Endovascular treatment of aneurysms is an evolving technique. Endovascular
      techniques for the treatment of aneurysms have been available for 10 years.
      During this time, we have seen major advances and improvements in our ability to
      embolize aneurysms via an endoluminal approach. We have continued to modify our
      techniques and selection of patients who would most benefit from this approach.
      This article summarizes the current literature and attempts to develop a
      management strategy toward improving patient outcome by optimizing the choice
      between endovascular and surgical treatment modalities.

PMID- 12074444
TI  - Aneurysm observation versus intervention: a literature review.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) is a devastating illness that affects
      persons at the peaks of their lives. The 1990s witnessed rapid growth in
      noninvasive vascular imaging technologies, which allowed safe diagnosis of
      unruptured saccular intracranial aneurysms. Presently, it is unclear who will
      benefit from screening. Mass screening is neither feasible nor cost-effective.
      The current literature suggests that persons in a family with two or more
      relatives with a history of SAH are most likely to benefit from screening.
      Individuals with a history of SAH, with aneurysms greater than 10 mm in diameter
      or with symptomatic aneurysms are clearly at increased risk for SAH. These
      aneurysms should be treated, though the method of treatment remains open to
      question. Treatment of older patients or those with smaller aneurysms has been
      modeled by decision analysis, but has yet to be verified in a prospective
      clinical trial. Future directions for aneurysm management are explored.

PMID- 12074445
TI  - The licensure dilemma.

PMID- 12074447
TI  - Surface analysis of anodic oxide films containing phosphorus on titanium.
AB  - PURPOSE: To examine the effect of phosphoric acid solution on the anodic oxide
      film of titanium. MATERIALS AND METHODS: Commercially pure grade 2 titanium
      specimens were prepared and anodized in phosphoric acid solution at a constant
      current density (70 A/m2). Specimens were evaluated by means of scanning electron
      microscopy, x-ray diffraction analysis, electron probe microanalysis, energy
      dispersive spectroscopy, profilometry, and atomic force microscopy. RESULTS: The
      anodic oxide film was observed to consist of a porous or non-uniform layer and a
      dense or uniform layer. X-ray diffraction and energy-dispersive spectroscopic
      analyses indicated that the film consisted of a mixture of anatase and amorphous
      oxide, with the incorporation of phosphorus. DISCUSSION: The degree of oxide
      crystallinity was observed to increase with an increase in voltage but decreased
      as the electrolyte concentration was increased. In addition, the concentration of
      phosphorus also increased as the electrolyte concentration and voltage increased.
      CONCLUSIONS: Electrolyte concentration and voltage play an important role in
      governing the anodic oxide thickness, composition, and degree of oxide
      crystallinity.

PMID- 12074446
TI  - In vitro osteoclast resorption of bone substitute biomaterials used for implant
      site augmentation: a pilot study.
AB  - PURPOSE: This observational study examined the resorptive behavior of normal
      neonatal rabbit osteoclasts grown on slices of bovine cortical bone as compared
      to samples of commercially available bone substitute biomaterials. It also
      examined the surface characteristics of these materials. MATERIALS AND METHODS:
      The 11 materials tested fell into 3 groups: (1) bone-derived, including freeze
      dried human rib block, human demineralized freeze-dried bone, and deproteinated
      bovine bone; (2) synthetic hydroxyapatites (HA); and (3) synthetic non-HA,
      including coated methacrylates and coated silica glass. After 4 days in culture,
      1 group of samples of each material underwent scanning electron microscopy (SEM)
      to evaluate resorptive pitting versus controls, while another group underwent
      tartrate-resistant acid phosphatase staining and light microscopy to examine
      osteoclast numbers and morphology. The 2 bovine-derived HA materials also
      underwent immunohistochemical staining and surface chemistry analysis. RESULTS:
      While most of these materials supported osteoclast attachment, some spreading,
      and survival in culture, only the bone-derived materials, with the exception of
      sintered deproteinated bovine bone, showed large scalloped-edged resorption pits
      with trails and exposed collagen when examined by SEM, although not to the same
      extent as unprocessed natural bone material. The HA materials and the sintered
      deproteinated bovine bone showed evidence of etching with smaller pits but no
      evidence of resorptive trail formation. The non-HA materials showed no evidence
      of pit formation or trails. Under immunohistochemical staining, Bio-Oss appeared
      to be positive for type I collagen after osteoclast activity on its surface,
      while Osteograf/N showed no positive staining. Surface chemistry analysis
      revealed nitrogen present in Bio-Oss specimens (0.17% to 0.47%), while there was
      no nitrogen detected in the Osteograf/N (0.00%); the percent nitrogen observed in
      normal bovine bone controls was 6.01% to 9.25%. DISCUSSION: The bone-derived
      materials supported osteoclast activity on the material surface in a way that
      facilitated formation of the more complex resorption pits in vitro. Assuming the
      rate of pit formation observed in vitro mimics that observed in vivo, the
      quantity and type of osteoclastic remodeling seen on non-bone-derived materials-
      and perhaps sintered bone-derived materials--would be extremely slow to
      negligible. Physiologic removal of non-bone-derived bone substitutes in vivo may
      occur by methods other than osteoclast resorption. CONCLUSIONS: Allogenous and
      xenogenous bone-derived materials that undergo delayed physiologic resorption may
      be more appropriately used with a staged surgical approach when used in sites
      intended to support osseointegrated dental implants. The combination of collagen
      staining and the presence of nitrogen suggest that there may be residual protein
      in Bio-Oss.

PMID- 12074448
TI  - Porous hydroxyapatite for grafting the maxillary sinus: a comparative
      histomorphometric study in sheep.
AB  - PURPOSE: This experimental study in adult female sheep examined the value of
      nonresorbable porous hydroxyapatite (HA) as a grafting material in a single-stage
      sinus-lift procedure. MATERIALS AND METHODS: Two titanium plasma-flame-sprayed
      cylindric implants were placed bilaterally in each of 54 sinuses in 27 adult
      female sheep. In 2 groups of 18 sinuses each, the subantral hollow space was
      filled with porous HA or autogenous cancellous bone harvested from the iliac
      crest, respectively. Eighteen sinuses were not augmented and served as controls.
      The time course of new bone formation and bone remodeling was evaluated by
      sequential polyfluorochrome labeling. Observation periods were 12, 16, and 26
      weeks after the surgical procedure. Six sinuses per observation period and test
      group were available for histologic evaluation. RESULTS: All implants were
      osseointegrated in the local host bone. New bone formation was observed in a
      triangular area bounded by the implant surface, local buccal antral wall, and
      submucous connective tissue around all implants. The mean length of bone-implant
      contact was 3.9 +/- 0.3 mm in the control group, 5.7 +/- 0.3 mm in the autogenous
      bone group, and 5.9 +/- 0.3 mm in the group augmented with porous HA. During the
      observation period, the relative length of direct bone-implant contact increased
      from 20% to 25.1% in the control group, from 30.4% to 35.5% in the autogenous
      bone group, and from 29.8% to 41.7% in the HA group. At a distance of 1 mm from
      the implant, the mean bone volume was 29.7 +/- 15.7% in the autogenous bone
      group. In the group augmented with HA the mean bone volume was 11.2 +/- 13.0%.
      DISCUSSION: There was no significant difference between HA and autogenous bone
      regarding bone-implant contact (P = .89). CONCLUSIONS: Both groups showed a
      significantly greater bone-implant contact (HA: P = .002; autogenous bone: P =
      .0005) than the empty control group. However, since the results varied widely,
      the use of HA alone for sinus grafting should be used with discretion in sinus
      lift procedures.

PMID- 12074449
TI  - Bone density around titanium implants may be influenced by intermittent cigarette
      smoke inhalation: a histometric study in rats.
AB  - PURPOSE: This study investigated the influence of cigarette smoke on bone healing
      around titanium implants placed in rats. MATERIALS AND METHODS: After
      administration of anesthesia, the tibia surface was exposed and screw-shaped
      titanium implants (4.0 mm in length and 2.2 mm in diameter) were placed
      bilaterally (1 each side). The animals (n = 32) were randomly assigned to either
      group 1 (control, n = 18) or group 2 (intermittent cigarette smoke inhalation, n
      = 14). After 60 days, the animals were sacrificed and undecalcified sections
      obtained. Bone density (the proportion of mineralized bone in a 500-microm-wide
      zone lateral to the implant) was measured in the cortical (zone A) and cancellous
      bone (zone B) areas. RESULTS: In zone A, a slight difference in bone density was
      noted between the groups (96.18% +/- 1.08% and 95.38 +/- 1.17% in groups 1 and 2,
      respectively; P > .05) but was not statistically significant. In contrast, bone
      density was significantly decreased in zone B in the animals that were exposed to
      cigarette smoke (17.57 +/- 6.45% and 11.30 +/- 6.81% for groups 1 and 2,
      respectively; P < .05). DISCUSSION: Whether different results would be observed
      if animals were exposed to cigarette smoke for a longer period of time and/or
      before implant placement remains to be investigated. CONCLUSION: Although
      intermittent cigarette smoke exposure may not seriously affect cortical bone
      density, it may jeopardize bone quality around titanium implants in the
      cancellous bone area.

PMID- 12074450
TI  - Two dental implants designed for immediate loading: a finite element analysis.
AB  - PURPOSE: The aim of this study was to evaluate by finite element analysis the
      influence of the design of 3 different dental implants on micromovements,
      cervical shearing stress intensity, and stress distribution after occlusal
      loading. MATERIALS AND METHODS: The first investigated implant was a classical
      cylinder, the second was reinforced by 2 bicortical locking pins, and the third
      was an expanding dental implant. The parameters analyzed were the implant's
      geometry, the quality of the cancellous bone, and the orientation of occlusal
      loading. RESULTS: It was found that initial stability of the locking pin implant
      was greater than the initial stability of the other investigated implant designs,
      regardless of the quality of cancellous bone and orientation of occlusal loading;
      in low-rigidity cancellous bone, under a horizontal load (500 N), decreasing
      displacement compared to those of the other investigated implants was 16 microm.
      The apical expansion and locking pin implants exhibited favorable behavior
      regarding the distribution and intensity of cervical shearing stresses; in low
      rigidity cancellous bone, under horizontal load, decreasing cervical stresses
      compared with those of the cylindric implant were 10 MPa for the apical expansion
      implant and 150 MPa for the locking pin implant. DISCUSSION: For the cylindric
      implant, stresses were concentrated in the neck region; for the apical expansion
      implant, stresses were evenly distributed from the neck to the apex of the
      implant. For the locking pin implant, stresses around the neck were moderate and
      appeared concentrated around the pins. CONCLUSIONS: Initial stability of the pin
      implant was greater than that of the expanding implant, but the expanding implant
      showed the most favorable stress distribution.

PMID- 12074451
TI  - Cellular fibronectin in failing dental implants.
AB  - PURPOSE: Cellular fibronectin staining is decreased in adult periodontitis, which
      implies elastase-mediated degradation of periodontal tissues. The purpose of this
      study was to determine whether failing dental implants display similar changes.
      MATERIALS AND METHODS: Cellular fibronectin and its integrin receptors were
      identified by immunohistochemistry and quantified by computerized image analysis.
      RESULTS: Cellular fibronectin was found in blood vessel walls, epithelial
      basement membranes, and fibroblasts. Quantitative results of cellular fibronectin
      staining were as follows: failing dental implants, median 26.5% (Q3-Q1 = 23%);
      adult periodontitis, median 5.5% (Q3-Q1 = 5.6%); normal controls, median 12.2%
      (Q3-Q1 = 7.5%). Cellular fibronectin staining was increased around failing dental
      implants but decreased in adult periodontitis compared to healthy controls.
      DISCUSSION: The distribution of integrin receptor subunits alpha4, alpha5, and
      beta1 of cellular fibronectin was similar in failing dental implants. The
      pathomechanisms in adult periodontitis and failing dental implants seem to
      differ. CONCLUSIONS: Adult periodontitis is characterized by proteolysis/loss of
      cellular fibronectin, whereas failing dental implants are characterized by
      increased cellular fibronectin deposition, probably as a result of titanium
      induced local synthesis and relatively modest degradation.

PMID- 12074452
TI  - Histologic comparison of a thermal dual-etched implant surface to machined, TPS,
      and HA surfaces: bone contact in vivo in rabbits.
AB  - PURPOSE: To evaluate the bone contact percentage around a proprietary high
      temperature dual-etched (DE) implant surface (Osseotite) versus implants with
      machined, hydroxyapatite (HA), and titanium plasma-sprayed (TPS) surfaces.
      MATERIALS AND METHODS: Each implant type was placed in rabbit tibiae of the same
      animal and assessed at 1 to 8 weeks. Histologic sections were prepared and
      analyzed histomorphometrically. RESULTS: The DE implant surface achieved higher
      levels of bone contact percentage than the other surfaces. This enhanced contact
      level was apparent by 3 weeks and seen at all time intervals except 2 weeks, at
      which machined exceeded the DE mean. In evaluating which surface outscored the
      others in each individual rabbit, there was a statistically significant
      confidence for the DE surface (P < .001). The other 3 surfaces failed to show
      significance, although the numeric scores for the TPS surfaces were below random
      expectations and the machined scores were slightly above. There was no
      correlation between degree of roughness and bone contact percentage. DISCUSSION:
      Arbitrarily roughening the implant surface may not result in a large change in
      bone conductivity. The specific texture of the DE process yielded more contact,
      possibly as the result of better fibrin clot retention and growth factor
      enhancement. CONCLUSIONS: There was no advantage demonstrated in this model to an
      HA surface over titanium. The bone contact to the rough HA surface scored
      similarly to that for the TPS surface of similar roughness, and well below that
      for the DE titanium surface. The DE surface appeared to have an advantage in bone
      contact percentage, particularly in early healing in a rabbit tibia model.

PMID- 12074453
TI  - Histomorphometric analysis of the bone-implant contact obtained with 4 different
      implant surface treatments placed side by side in the dog mandible.
AB  - PURPOSE: The different implant systems available today present several types of
      surface treatment, with the aim of optimization of bone-implant contact. This
      study compared 4 different types of implant surfaces. MATERIALS AND METHODS: The
      first, second, third, and fourth mandibular premolars were extracted from 5 young
      adult mongrel male dogs. Ninety days after removal, four 3.75-mm-diameter, 10-mm
      long screw-type implants (Paragon) were placed with different surface treatments
      in mandibular hemiarches. The dogs received 2 implants of each of the following
      surface treatments: smooth (machined), titanium plasma spray (TPS),
      hydroxyapatite coating (HA), and sandblasting with soluble particles (SBM). The
      implants were maintained unloaded for 90 days. After this period, the animals
      were sacrificed, and the hemimandibles were extracted and histologically
      processed to obtain non-decalcified sections. Two longitudinal ground sections
      were made for each implant and analyzed under light microscopy coupled to a
      computerized system for histomorphometry. RESULTS: The following means were
      obtained for bone-implant contact percentage: machined = 41.7%, TPS = 48.9%, HA =
      57.9%, and SBM = 68.5%. DISCUSSION: The means for all treatments that added
      roughness to the implant surface were numerically superior to the mean found for
      the machined surface. However, this difference was statistically significant only
      between groups SBM and machined (Tukey test, P < .05). CONCLUSIONS: The SBM
      treated surface provided a greater bone-implant contact than a machined surface
      after 90 days without loading in this model.

PMID- 12074454
TI  - The influence of controlled occlusal overload on peri-implant tissue. part 4: a
      histologic study in monkeys.
AB  - PURPOSE: The purpose of this study was to observe, after removing occlusal trauma
      and conducting plaque control, possible macroscopic and histologic changes in
      peri-implant tissue that had deteriorated resulting from experimental peri
      implantitis, and to investigate the necessity for treatment procedures for peri
      implantitis. MATERIALS AND METHODS: Four monkeys (Macaca fascicularis) in good
      general health were used in this experiment. Three months after the second
      premolar and the first molar were extracted from the right mandible, 2 IMZ
      experimental implants were placed in each monkey. After a 3-month
      osseointegration period, a second surgery was conducted, followed by making an
      impression for fabrication of the prosthesis. Excessive occlusal height of the
      prosthesis was adjusted to 250 microm, and the experiment was continued for 8
      weeks after placement of the prosthesis. Three models were created: (1) A
      superstructure with an excessive occlusal height was used for 8 weeks without any
      brushing (positive control, model P); (2) after the first 4 weeks with a
      prosthesis with excessive occlusal height and no brushing, the superstructure was
      removed and not used for the last 4 weeks while brushing was conducted
      (experimental model, model E); and (3) for 8 weeks, a prosthesis with an
      appropriate occlusal height was used with brushing (negative control, model N).
      RESULTS: When these 3 models were compared with each other, macroscopic findings
      indicated inflammation only in model P. Mobility of implants was not seen in any
      model. Histopathologic observations revealed a slight difference between model E
      and model P in terms of the degree of inflammatory cell infiltration in the
      connective tissue. DISCUSSION: No difference was found in the degree of bone
      resorption. Partial tearing was observed at the contact region between epithelial
      tissue and implant surfaces. CONCLUSIONS: (1) The contact between implants and
      epithelial or connective tissue is fragile; (2) inflammation and occlusion must
      be controlled more prudently than in the case of natural teeth; and (3) once peri
      implantitis has progressed, the control of occlusion and inflammation is probably
      not sufficient to promote the healing mechanism.

PMID- 12074455
TI  - One-year prosthetic outcomes with implant overdentures: a randomized clinical
      trial.
AB  - PURPOSE: This randomized clinical trial examined implant overdenture (IOD)
      fabrication and maintenance time and costs, adjustment and repair incidence, and
      patient satisfaction after 1 year. MATERIALS AND METHODS: Sixty-four patients
      received 2 mandibular implants and an IOD with either a bar with 2 clips or 2
      ball attachments for denture retention. RESULTS: Fabrication time, number of
      appointments, and chair time for adjustments were similar for the 2 denture
      designs. The most common adjustments for both types were to the IOD contours.
      Ball-attachment dentures required about 8 times longer for repairs than bar-clip
      prostheses. Approximately 84% of patients with ball-attachment dentures needed at
      least 1 repair, versus 20% of those with a bar-clip mechanism. The most common
      repairs were replacement of the cap spring or cap for the ball-attachment IOD and
      replacement of a lost or loose clip for bar-clip dentures. DISCUSSION: Patients
      were equally and highly satisfied with the improvements in function, comfort, and
      appearance with both types of IOD compared to their original conventional
      dentures. CONCLUSIONS: Given equivalent levels of patient satisfaction with
      either method of retention and a much higher repair rate for the ball attachment,
      it is suggested that a bar-clip design be used rather than the particular ball
      attachment utilized in this study.

PMID- 12074456
TI  - A retrospective radiographic analysis of bone loss following placement of TiO2
      grit-blasted implants in the posterior maxilla and mandible.
AB  - PURPOSE: Cortical bone is a determinant of implant esthetics and may contribute
      to the biomechanical integrity of the implant-supported prosthesis. Historically,
      approximately 1.0 to 1.5 mm of bone loss has occurred immediately following
      second-stage surgery and implant loading. Recent consideration of implant design
      suggests that surface topography may affect crestal bone responses at the implant
      interface. The aim of this retrospective study of 102 implants in 48 subjects
      supporting posterior fixed partial dentures was to radiographically define the
      behavior of crestal bone at TiO2 grit-blasted implants following surgical
      placement and subsequent loading in the posterior maxilla and mandible. MATERIALS
      AND METHODS: The crestal bone position relative to the implant reference point
      (junction of the crestal bevel with the TiO2 grit-blasted surface) was evaluated
      at implant placement, at abutment placement, and 6 to 36 months following
      restoration, with an average recall period of 2.3 years. The implant position and
      dimension were recorded. A single investigator using 7x magnification assessed
      all radiographs. RESULTS: Crestal bone loss from the time of implant placement up
      to 36 months following restoration ranged from 0.0 to 2.1 mm. Of the 102
      implants, 14 implants showed greater than 1.0 mm of crestal bone loss. They were
      not clustered at any particular tooth position. Eighty of the implants showed
      less than 0.5 mm of radiographically measured bone loss. Mean crestal bone loss
      was 0.36 mm (+/- 0.6 mm). Averages of 0.57 and 0.24 mm loss were shown for 3.5-
      and 4.0-mm-diameter implants, respectively (P < .051). Bone gain was seen at
      several 4.0-mm-diameter implants. DISCUSSION: This retrospective evaluation
      indicates that the radiographically measured bone loss may be expected to be less
      than 1 mm following placement and loading of TiO2 grit-blasted implants. The
      close approximation of bone with the implant/abutment interface suggests the
      attenuation of any microgap-induced bone loss. Additional reasons for crestal
      bone maintenance may include factors attributed to implant surface roughness and
      loading along a tapered implant/abutment interface. CONCLUSIONS: Several clinical
      advantages for maintaining crestal bone at implants supporting posterior
      prostheses can be identified.

PMID- 12074457
TI  - A histomorphometric analysis of heavily loaded and non-loaded implants.
AB  - PURPOSE: To investigate the bone tissue response at the interface of loaded and
      non-loaded implants used in an orthopedic anchorage system after a continuous,
      non-axial force application of 5 N over 2 months. MATERIALS AND METHODS: Twenty
      nine Branemark System implants were placed in the zygomatic arches of 5 dogs.
      After a healing period of 8 weeks, 20 implants (4 in each dog) were loaded during
      8 weeks with a large non-axial orthopedic force application of 5 N. This force
      was directed between the implants and a maxillary splint to move the maxilla
      forward. Nine implants were not loaded during this period. At the termination of
      the experiment, all 29 implants were retrieved for radiographic as well as for
      histologic analysis. Computer-based histomorphometric quantifications were
      performed via light microscopy and computer software. Bone-metal contact (BMC),
      bone surface area (BSA) inside the threads, and the bone mirror area (BMA) of the
      implants were measured. Statistical comparisons between the loaded and non-loaded
      implants were carried out. In the group of loaded implants a 2-factor analysis of
      variance was used. RESULTS: There were no statistically significant differences
      found in BMC, BSA, and BMA between the loaded and non-loaded implants, both for
      all the threads and for only the cervical region of the implants. Nor were there
      statistically significant differences between the non-pressure and pressure sides
      or for different lengths of the loaded implants. DISCUSSION: The loaded implants
      maintained the osseointegration achieved during the 8-week healing period.
      CONCLUSIONS: The results of this study indicate that titanium implants can be
      used as anchorage for orthopedic force application systems.

PMID- 12074459
TI  - Anteroinferior distraction of the atrophic subtotal maxillary alveolus for
      implant placement: a case report.
AB  - Most reports on alveolar distraction have been related to vertical distraction in
      the mandible and the maxilla. There have been few reports on horizontal or
      oblique alveolar distraction. A case of an atrophic subtotal maxillary alveolus
      distracted 10 mm anteriorly and 5 mm vertically, followed by the placement of 9
      implants, is presented. A healthy, 55-year-old woman presented with a chief
      complaint of mobility of all maxillary teeth. All remaining 11 teeth except the
      maxillary left second molar were diagnosed as being involved with advanced
      marginal periodontitis, and were considered hopeless and subsequently extracted.
      Three months after extraction, a horizontal osteotomy was performed with a bone
      saw between the bilateral second premolar regions, extending vertically distal to
      the second premolars, without involving the maxillary sinuses. After confirming
      mobility of the alveolar bone, a distraction device was seated with titanium
      miniscrews and adhesive resin cement over the hard palate. After a 7-day waiting
      period, the maxillary alveolus was distracted anteroinferiorly 0.25 mm twice a
      day for 25 consecutive days. The distraction process was completed uneventfully.
      Postdistraction computed tomography demonstrated that the maxillary alveolus was
      adequately distracted to place implants in an ideal position. Nine endosseous
      implants were placed 4 months after seating the distraction device. All implants
      had good primary stability and were submerged. All implants osseointegrated,
      although 2 anterior implants were replaced due to disintegration resulting from
      transmucosal overloading of the interim removable prosthesis. No significant
      marginal bone resorption was seen around the implants 16 months after implant
      placement. It was concluded that alveolar distraction can be very useful for
      augmenting the atrophic alveolus, not only vertically but also horizontally or
      obliquely.

PMID- 12074458
TI  - Medicolegal aspects of altered sensation following implant placement in the
      mandible.
AB  - PURPOSE: Altered mandibular sensation following implant surgery may result in
      liability claims. Therefore the authors conducted a retrospective analysis of all
      liability claims related to persistent altered sensation following placement of
      mandibular implants reported to the Medical Consultants International (MCI)
      Company from 1992 to 1999. MATERIALS AND METHODS: Reports related to persistent
      altered mandibular sensation in 16 patients (12 women and 4 men) who underwent
      implant surgery in Israel were examined. The MCI files were retrospectively
      evaluated according to a structured form. The parameters studied included patient
      age and gender, implant location and length, imaging modality, and the time
      between actual damage and filing of a claim (ie, letter of demand or lawsuit).
      RESULTS: The time in months between actual damage and filing of claim ranged from
      0 to 60 months (mean 21.5 months). No cases were found involving transient
      changes in sensation. The female/male ratio was 3:1. Implant length was equal to
      or longer than 13 mm in 6 of 7 implants placed in the molar region. In the
      premolar area, nerve injury was evident in 6 of 7 cases where implants shorter
      than 12 mm were used. CONCLUSIONS: Transient nerve injury rarely results in legal
      action. Maximum effort should be devoted to accurately determining the
      appropriate implant length in the mandible.

PMID- 12074461
TI  - Clinical experience with intensity-modulated radiation therapy (IMRT) for
      prostate cancer with the use of rectal balloon for prostate immobilization.
AB  - The implementation of intensity-modulated radiation therapy (IMRT) is the result
      of advances in imaging, radiotherapy planning technologies, and computer
      controlled linear accelerators. IMRT allows both conformal treatment of tumors
      and conformal avoidance of the surrounding normal structures. The first patient
      treated with Peacock IMRT at Baylor College of Medicine took place in March 1994.
      To date, more than 1500 patients have been treated with IMRT; more than 700
      patients were treated for prostate cancer. Our experience in treating prostate
      cancer with IMRT was reviewed. Patient and prostate motions are important issues
      to address in delivering IMRT. The Vac-Lok bag-and-box system, as well as rectal
      balloon for immobilization of patient and prostate gland, respectively, are
      employed. Treatment planning also plays a very important role. IMRT as a boost
      after conventional external beam radiotherapy is not our treatment strategy. To
      derive maximal benefits with this new technology, all patients received full
      course IMRT. Three separate groups of patients receiving (1) primary IMRT, (2)
      combined radioactive seed implant and IMRT, and (3) post-prostatectomy IMRT were
      addressed. Overall, toxicity profiles in these patients were very favorable. IMRT
      has the potential to improve treatment outcome with dose escalation while
      minimizing treatment-related toxicity.

PMID- 12074460
TI  - Use of the buccal fat pad in maxillary and sinus grafting of the severely
      atrophic maxilla preparatory to implant reconstruction of the partially or
      completely edentulous patient: technical note.
AB  - PURPOSE: To examine the use of the buccal fat pad (BFP) for correction of
      maxillary osseous defects, preliminary to dental implant reconstructions, and to
      present patients in whom this technique was used. MATERIALS AND METHODS: The
      blood supply of the BFP was investigated with a special laser Doppler flowmetry
      fiberoptic probe in situ before herniation and after placement of the pedicled
      BFP over maxillary bone grafts. RESULTS: The possibility of using the BFP pedicle
      flap to provide an immediate blood supply to a recipient site was confirmed, as
      it promotes rapid neo-vascularization of the grafted material over which it is
      placed. No complications were seen in the present patients. DISCUSSION: The BFP
      has an additional protective function of providing for a multiple-layer wound
      closure over all types of maxillary bone grafts, thereby preventing graft
      exposure and enhancing success. CONCLUSIONS: With its high blood flow, the BFP
      may offer protection and early blood supply to maxillary and sinus bone grafts.

PMID- 12074462
TI  - Intensity-modulated radiation therapy in the treatment of children.
AB  - Intensity-modulated radiation therapy (IMRT) is a relatively new method of
      conformal radiotherapy delivery that is rapidly being incorporated in clinical
      practice. Of all patients treated with conformal techniques, children are the
      most likely to benefit as normal, developing structures can be minimized in the
      radiation field. The advantages of IMRT, including increased conformality and
      possible dose escalation, are discussed in this review. Possible disadvantages of
      IMRT in children are also discussed, such as lack of dose homogeneity in the
      target volume, increased dose to nontarget tissues, reliability of treatment
      setup, increased anesthesia time in younger children, and prolonged treatment
      planning. The issue of increased risk of second malignancy in this very young
      population is important, as many of these children will be long-term survivors
      with current multimodality therapy.

PMID- 12074464
TI  - Intensity-modulated radiation therapy in gynecologic malignancies.
AB  - Radiation therapy (RT) is commonly used in the treatment of gynecologic
      malignancies. Unfortunately, RT exposes patients to a wide variety of sequelae.
      Concerns over toxicity also limit the use of higher doses in select patients. To
      improve the efficacy of conventional RT and to explore the possibility of dose
      escalation, we have turned to the use of intensity-modulated RT (IMRT). This
      report reviews our preclinical studies, implementation, and clinical experience
      to date with IMRT for gynecologic malignancies.

PMID- 12074463
TI  - Treatment of pancreatic cancer tumors with intensity-modulated radiation therapy
      (IMRT) using the volume at risk approach (VARA): employing dose-volume histogram
      (DVH) and normal tissue complication probability (NTCP) to evaluate small bowel
      toxicity.
AB  - The emergent use of a combined modality approach (chemotherapy and radiation) in
      pancreatic cancer is associated with increased gastrointestinal toxicity.
      Intensity-modulated radiation therapy (IMRT) has the potential to deliver
      adequate dose to the tumor volume while decreasing the dose to critical
      structures such as the small bowel. We evaluated the influence of IMRT with
      inverse treatment planning on the dose-volume histograms (DVHs) of normal tissue
      compared to standard 3-dimensional conformal radiation treatment (3D-CRT) in
      patients with pancreatic cancer. Between July 1999 and May 2001, 10 randomly
      selected patients with adenocarcinoma of the pancreatic head were planned
      simultaneously with 3D-CRT and inverse-planned IMRT using the volume at risk
      approach (VaRA) and compared for various dosimetric parameters. DVH and normal
      tissue complication probability (NTCP) were calculated using IMRT and 3D-CRT
      plans. The aim of the treatment plan was to deliver 61.2 Gy to the gross tumor
      volume (GTV) and 45 Gy to the clinical treatment volume (CTV) while maintaining
      critical normal tissues to below specified tolerances. IMRT plans were more
      conformal than 3D-CRT plans. The average dose delivered to one third of the small
      bowel was lower with the IMRT plan compared to 3D-CRT. The IMRT plan resulted in
      one third of the small bowel receiving 30.2+/-12.9 Gy vs. 38.5+/-14.2 Gy with 3D
      CRT (p = 0.006). The median volume of small bowel that received greater than
      either 50 or 60 Gy was reduced with IMRT. The median volume of small bowel
      exceeding 50 Gy was 19.2+/-11.2% (range 3% to 45%) compared to 31.4+/-21.3 (range
      7% to 70%) for 3D-CRT (p = 0.048). The median volume of small bowel that received
      greater than 60 Gy was 12.5+/-4.8% for IMRT compared to 19.8+/-18.6% for 3D-CRT
      (p = 0.034). The VaRA approach employing IMRT techniques resulted in a lower dose
      per volume of small bowel that exceeded 60 Gy. We used the Lyman-Kutcher models
      to compare the probability of small bowel injury employing IMRT compared to 3D
      CRT. The BIOPLAN model predicted a small bowel complication probability of 9.3+/
      6% with IMRT compared to 24.4+/-18.9% with 3D-CRT delivery of dose (p = 0.021).
      IMRT with an inverse treatment plan has the potential to significantly improve
      radiation therapy of pancreatic cancers by reducing normal tissue dose, and
      simultaneously allow escalation of dose to further enhance locoregional control.

PMID- 12074465
TI  - Intensity-modulated radiation therapy for the spine at the University of
      California, Irvine.
AB  - Radiation treatment of malignant diseases of the spine poses unique challenges to
      the radiation oncology treatment team. Intensity-modulated radiation therapy
      (IMRT) offers the capability of delivering high doses to targets near the spine
      while respecting spinal cord tolerance. At the University of California, Irvine,
      8 patients received a total of 10 courses to the spine for a variety of primary
      and metastatic malignant conditions. This paper discusses anatomical
      considerations, spinal cord radiation myelopathy, and treatment planning issues
      as it relates to the treatment of spinal cord lesions. Between October 1997 and
      August 2001, a total of 8 patients received 10 courses of IMRT for primary or
      metastatic disease of the spine. Cancers treated included metastatic lung, renal,
      adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had
      6 courses given for re-irradiation of symptomatic disease and 3 cases had 4
      courses of IMRT as primary management of their spinal lesions. Although 3 courses
      were given postoperatively, these were for grossly residual disease. For the re
      irradiation patients, the mean follow-up interval was 4 months. The local control
      was estimated at 14%. Of the patients treated with primary intent, the mean
      follow-up was 9 months and the local control rate 75%. No patients developed
      spinal cord complications.

PMID- 12074466
TI  - Fractionated stereotactic intensity-modulated radiotherapy (FS-IMRT) for small
      acoustic neuromas.
AB  - Eight patients with acoustic neuromas were treated using a novel method developed
      at our institution for delivering fractionated stereotactic intensity-modulated
      radiotherapy (FS-IMRT). We present treatment parameters, dosimetry analysis, and
      preliminary clinical outcome. The method incorporates high-precision invasive
      fixation, obliquely-oriented tomotherapy arcs, and reduced dimension pencil
      beams. The delivered dose distributions for the 8 patients treated from April
      1999 to May 2001 were assessed for dose conformality, homogeneity, and doses to
      organs at risk. Total doses prescribed were 54 Gy in daily doses of 1.8 Gy.
      Results show that the median planning target volume (gross tumor volume plus a
      safety margin of 2 mm) was 2.48 cm3 (1.64 to 16.86 cm3) and that the median
      conformality and homogeneity indices were 1.69 (1.56 to 2.16) and 1.12 (1.09 to
      1.19), respectively. The respective average mean and maximum doses to the brain
      stem were 12.67 Gy and 53.86 Gy. The treatment parameters for the novel FS-IMRT
      method developed here document excellent dose conformality and normal tissue
      sparing. Preliminary short-term follow-up (mean 17, median 18.5 months) revealed
      a 100% local control and hearing preservation rate. No new persistent impairment
      of facial and trigeminal nerve was observed. Our current follow-up experience
      indicates a reasonable potential for achieving outcomes comparable to established
      stereotactic radiotherapy techniques.

PMID- 12074467
TI  - Intensity-modulated radiation therapy (IMRT): the radiation oncologist's
      perspective.
AB  - Intensity-modulated radiation therapy (IMRT) is a new and evolving technological
      advance in high-precision radiation therapy. It is an extension of 3-dimensional
      conformal radiotherapy (3D-CRT) that allows the delivery of highly complex
      isodose profiles to the target while minimizing radiation exposure to surrounding
      normal tissues. Clinical data on IMRT are emerging and being collected, as more
      institutions are implementing or expanding the use of IMRT. However, the
      currently available IMRT and its applications are far from being well understood
      and established. In some circumstances, it remains impractical and too costly.
      This article discusses some practical issues from the radiation oncologist's
      perspective.

PMID- 12074468
TI  - Clinical implementation of intensity-modulated radiation therapy.
AB  - The clinical implementation of intensity-modulated radiation therapy (IMRT) is a
      complex process because of the introduction of new treatment planning algorithms
      and beam delivery systems compared to conventional 3-dimensional conformal
      radiation therapy (3D-CRT) and the lack of established national performance
      protocols. IMRT uses an inverse-planning algorithm to create nonuniform fields
      that are only deliverable through a newly designed beam-modulating delivery
      system. The intent of this paper is to describe our experience and to elucidate
      the new clinical procedures that must be executed to have a successful IMRT
      program. Patients who undergo IMRT at our institution are immobilized and
      simulated before proceeding to computed tomography scan for patient data
      acquisition. Treatment planning involves the use of different prescription dose
      formats and different planning techniques compared to 3D-CRT. The desired dose
      goals for the target and sensitive structures must be specified before initiating
      the planning process, which is computer intensive. After the plan is completed,
      the delivery instructions are transferred to the delivery system via either a
      floppy disk for MIMiC-based IMRT or through the network for MLC-based IMRT.
      Target localizations are carried out using orthogonal radiographs. Ultrasound
      imaging system (BAT) is used to localize the prostate. Dose validation is
      performed using films, ion chambers or dose-calculation-based techniques.

PMID- 12074469
TI  - Intensity-modulated radiotherapy for previously irradiated, recurrent head-and
      neck cancer.
AB  - The purpose of this work is to evaluate our initial experience in treating
      previously irradiated, recurrent head-and-neck cancers using intensity-modulated
      radiotherapy (IMRT). Between July 1997 and September 1999, 12 patients with
      previously irradiated, locally recurrent head-and-neck cancers were treated with
      IMRT. These included cancers of the nasopharynx, oropharynx, hypopharynx, larynx,
      paranasal sinus, skin of the head-and-neck region, and malignant melanoma. Five
      of these 12 patients had received radiation as the primary treatment, with doses
      ranging from 66.0 to 126.0 Gy, and the remaining 7 patients had undergone
      definitive surgeries followed by an adjuvant course of radiation treatment, with
      doses ranging between 36.0 and 64.8 Gy. Recurrence after the initial course of
      radiation occurred in periods ranging from 4 to 35 months, with 11 of 12 cases
      recurring fully in the fields of previous irradiation. Recurrent tumors were
      treated with IMRT to total doses between 30 to 70 Gy (> 50 Gy in 10 cases)
      prescribed at the 75% to 92% isodose lines with daily fractions of 1.8 to 2 Gy.
      The results revealed that acute toxicities were acceptable except in 1 patient
      who died of aspiration pneumonia during the course of retreatment. There were 4
      complete responders, 2 partial responders, and 2 patients with stable disease in
      the IMRT-treated volumes. Three patients received IMRT as adjuvant treatment
      following salvage surgery. At 4 to 16 months of follow-up, 7 patients were still
      alive, with 5 revealing no evidence of disease. In conclusion, this pilot study
      demonstrates that IMRT offers a viable mode of re-irradiation for recurrent head
      and-neck cancers in previously irradiated sites. Longer follow-up time and a
      larger number of patients are needed to better define the therapeutic advantage
      of IMRT in recurrent, previously irradiated head-and-neck cancers.

PMID- 12074471
TI  - Clinical aspects of IMRT--part III.

PMID- 12074470
TI  - Technical considerations in the application of intensity-modulated radiotherapy
      as a concomitant integrated boost for locally-advanced cervix cancer.
AB  - The technical aspects of IMRT applied to cervix cancer are discussed in this
      paper, as well as issues related to tumor delineation, target volume definitions,
      inverse planning, and IMRT delivery. A theoretical example illustrating how IMRT
      can accurately mimic dose distributions obtained using conventional planning plus
      HDR brachytherapy is also shown. The notion of clinical optimization parameters
      is introduced to account for the radiation delivery variables, which affect the
      overall treatment time. This is especially relevant to the possible introduction
      of intrafractional movement and resulting inaccuracy, as well as facility
      efficiency.

PMID- 12074473
TI  - Clinical experience of head-and-neck cancer IMRT with serial tomotherapy.
AB  - New radiotherapy planning and delivery techniques are undergoing rapid progress
      and change due to computer hardware and software technologies that have led to
      the development of sophisticated 3-dimensional (3D) radiation treatment planning
      and computer-controlled radiation therapy delivery systems. Intensity-modulated
      radiation therapy (IMRT) is the most recent and advanced form of external beam
      radiation therapy often used to perform 3D conformal radiotherapy. It represents
      one of the most important technical advances in radiotherapy. IMRT has the
      potential to achieve a much higher degree of target conformity and normal tissue
      sparing than most other treatment techniques, especially for target volumes at
      risk with complex shapes and concave regions such as head-and-neck cancer. In
      this review, we summarize our own IMRT treatment techniques with serial
      tomotherapy and our clinical experience with 126 patients with head-and-neck
      IMRT.

PMID- 12074472
TI  - Intensity-modulated radiotherapy of the female breast.
AB  - Current methods for intensity-modulated radiotherapy (IMRT) in breast cancer use
      forward planning based on equivalent radiological path length to design intensity
      modulated tangential beams. Compared to conventional tangential techniques, dose
      reduction of organs at risk is limited using these techniques. We developed a
      method for intensity modulation of multiple beams for adjuvant radiotherapy of
      breast cancer by application of a virtual bolus defined on CT for inverse
      optimization. This method enables multibeam IMRT, which provides improved sparing
      of lung and heart tissue. In this paper, we present the general aspects of this
      approach and an evaluation of the optimum beam configuration for IMRT based on
      inverse treatment planning. We compared this method to conventional techniques.
      Different clinical examples illustrate the possible indications and feasibility
      of this new approach. This method is superior to conventional techniques because
      of the reduction of high-dose area of a substantial cardiac volume in those cases
      where the parasternal lymph nodes are part of the target volume.

PMID- 12074474
TI  - Clinical aspects of IMRT for head-and-neck cancer.
AB  - The tightly conformal doses produced by intensity-modulated radiotherapy (IMRT),
      the existence of many critical structures in close proximity to the target, and
      the lack of internal organ motion in the head and neck, provide the potential for
      organ sparing and improved tumor irradiation. Many studies of treatment planning
      for head-and-neck cancer have demonstrated the dosimetric superiority of IMRT
      over conventional techniques in these respects. The initial results of clinical
      studies demonstrate reduced xerostomia. They suggest an improvement in tumor
      control, which needs to be verified in larger studies and longer follow-up.

PMID- 12074476
TI  - The moral dignity of John P. Peters.

PMID- 12074475
TI  - John P. Peters: his role in diabetes, research, and patient care.

PMID- 12074478
TI  - The public man confronts a McCarthy era witch-hunt.

PMID- 12074477
TI  - John P. Peters and the committee of 430 physicians.
AB  - John Peters and his committee had a few basic goals. One was that local, state,
      and federal governments needed to provide money to construct facilities, support
      medical research and education, and care for the poor. And they wanted experts to
      call the shots. Over time, Peters and the committee got what they wanted for the
      most part: Hill-Burton money for building the hospitals, the rise of the National
      Institutes of Health, Medicare, Medicaid, a Veterans Administration system, and
      new and expanded medical schools. The experts calling the shots included David
      Kessler at the Food and Drug Administration and Surgeon General C. Everett Koop.
      In the halcyon days of American health system reform, back in 1993, Yale's Paul
      Beeson wrote about the Committee of 430 Physicians and its goals in the Pharos of
      Alpha Omega Alpha. Beeson was optimistic and he quoted from my 1991 JAMA health
      system reform editorial as a sharp contrast to what Fishbein had written -
      although coincidentally, we both quote Lincoln. My editorial began, "'with malice
      toward none, with charity for all...' so spoke Abraham Lincoln in his second
      inaugural address recognizing that he had no political consensus regarding either
      the constitutionality of states seceding or the morality of slavery being
      abolished. Nonetheless, he knew what was right and was able, through persuasive,
      often inspiring rhetoric, to conclude a bloody and decisive Civil War and
      constitute the foundation for this great republic.... Yet access to basic medical
      care for all of our inhabitants is still not a reality in this country. There are
      many reasons for this, not the least of which is a long-standing, systematic,
      institutionalized racial discrimination.... An aura of inevitablitiy is upon us.
      It is not acceptable morally, ethically, or economically for so many of our
      people to be medically uninsured or seriously underinsured. We can solve this
      problem. We have the knowledge and the resources, the skills, the time, and the
      moral prescience. We need only clear-cut objectives and proper organization of
      existing resources. Have we now the national will and leadership?" Beeson's
      answer to that question in 1993 was, "Yes, but not by one comprehensive act." He
      quoted Peters from his 1938 Annals of Internal Medicine article: "a sweeping
      program suddenly imposed in this country as a whole out of the head of any Jove
      would undoubtedly create confusion if not chaos. Thoughtful investigation and
      experiment promises more than grandiose projects born of emotional
      preconceptions. The programs must be built of an evolutionary manner, step by
      step." Very wise, very valid. But how long must our people wait?

PMID- 12074479
TI  - As remembered by a son.

PMID- 12074480
TI  - Clinical analysis of the related factors in acute appendicitis.
AB  - BACKGROUND: In order to determine reliable clues for early diagnosis of acute
      appendicitis, this study was conducted to examine the related factors in patients
      with clinically suspected acute appendicitis. METHODS: We retrospectively
      analyzed 282 patients with the clinical diagnosis of acute appendicitis at China
      Medical College Hospital in Taiwan from January to December 2000. To study the
      significant related factors of acute appendicitis, the t-test, chi-square
      analysis, and multivariate logistic regression analysis were used. RESULTS: There
      were 153 males (54.3 percent) and 129 females (45.7 percent). The mean age was
      30.3+/-17.4 years (range 1 to 81). The diagnostic rate of acute appendicitis was
      86.2 percent. If the combination of elevated C-reactive protein, leukocytosis and
      elevated neutrophil ratio was used, satisfactory specificity and positive
      predictive value were achieved in diagnosing acute appendicitis. After
      controlling for the other covariates, the multivariate logistic regression
      analysis showed that the significant related factors of acute appendicitis were
      male sex (odds ratio = 3.4; 95 percent confidence interval = 1.6 to 7.3; p <0.01)
      and elevated neutrophil ratio (odds ratio = 4.6; 95 percent confidence interval =
      2.0 to 10.6; p <0.001). CONCLUSIONS: If an elevated neutrophil ratio was
      observed, the probability of acute appendicitis was increased in patients with
      clinically suspected acute appendicitis. Thus, neutrophil ratio appears to be a
      good parameter for diagnosis of acute appendicitis in primary healthcare
      settings.

PMID- 12074482
TI  - Successful management of retinal tear post-laser in situ keratomileusis
      retreatment.
AB  - PURPOSE: To report a successful case management of a retinal tear post-Laser in
      situ Keratomileusis (LASIK) and retreatment. RESULTS: A patient with the history
      of ocular trauma underwent LASIK procedure for myopic astigmatism. Three months
      post-LASIK, she received additional excimer laser treatment for a symptomatic
      persistent central island. One month later; the patient experienced a flap tear
      at the edge of a prior chorioretinal scar. Retinal tear repair was successfully
      accomplished by indirect application of photocoagulation laser without damage to
      the corneal flap. CONCLUSIONS: To date, no definitive causal relationship has
      been established between retinal tear(s) and corneal refractive surgery. This
      report describes a retinal tear and repair, post-LASIK retreatment. The use of
      the indirect binocular argon laser alleviates the need to compress the LASIK flap
      and minimizes the potential for creating flap folds and striae, especially in the
      early post operative period. Clinicians should be on alert to consider this
      possible complication, post-LASIK and excimer laser; especially within a
      population whose clinical findings place them at greater risk.

PMID- 12074481
TI  - Immunolocalization of a guinea pig sperm surface antigen recognized by a
      monoclonal antibody E74.
AB  - E74 is a mouse monoclonal antibody raised against the acrosome-reacted guinea pig
      spermatozoa. This study describes immunolocalization of the E74 antigen in guinea
      pig spermatozoa. Immunoelectron microscopy of guinea pig spermatozoa shows that
      the E74 antigen is localized on the equatorial segment plasma membrane following
      the acrosome reaction but not associated with the surface of the acrosome-intact
      spermatozoa. Immunoblot analysis of Triton X-100 extract of cauda epididymal
      guinea pig spermatozoa following one-dimensional sodium dodecyl sulphate
      polyacrylamide gel electrophoresis shows that E74 antibody recognizes a protein
      with an apparent molecular weight of 45,000 dalton. Immunoblot of sperm extracts
      separated by two dimensional gel electrophoresis indicates a broad spot of 45,000
      dalton in the 5 to 7.5 isoelectric focusing range.

PMID- 12074483
TI  - Summary report of the experiments conducted at Pouilly-le-Fort, near Melun, on
      the anthrax vaccination, 1881.

PMID- 12074484
TI  - Terrorism from a public health perspective.
AB  - The use of biological and chemical weapons as agents of warfare and terrorism has
      occurred sporadically, but recent events demonstrate the increasing risk and
      possibility that terrorist groups with grievances against the government or
      groups may employ them. Historically, most evaluations of the potential risk for
      biological weaponry have focused on the military, but the recent release of
      anthrax in the United States demonstrates that civilian populations are also at
      risk. More likely than not, most bioterrorism events will be of a small scale;
      however, agents such as Bacillus anthracis and Yersinia pestis could leave
      hundreds of thousands dead or incapacitated. The impact of the attack will depend
      on a number of variables, including the agent used, method of dispersal, and the
      responsiveness of the public health system. With any large-scale event, the
      public health infrastructure will be called upon to deal with mass casualties and
      the "worried well."

PMID- 12074485
TI  - Bacterial pathogens as biological weapons and agents of bioterrorism.
AB  - Bacterial pathogens have been identified as agents that have been, or could be,
      used as weapons of biological warfare and/or biological terrorism. These agents
      are relatively easily obtained, prepared, and dispersed, either as weapons of
      mass destruction or for more limited terrorist attacks. Although phylogenetically
      diverse, these agents all have the potential for aerosol dissemination.
      Physicians in the United States and most of the developed world have never
      encountered most of these agents and the diseases they produce. Public health
      programs must be prepared, and individual primary care providers must be able to
      recognize, diagnose, treat, and prevent infection with these agents.

PMID- 12074486
TI  - Viral agents as biological weapons and agents of bioterrorism.
AB  - Multiple viral agents have been classified by the CDC as potential weapons of
      mass destruction or agents for biologic terrorism. Agents such as smallpox, viral
      hemorrhagic fever viruses, agents of viral encephalitis, and others are of
      concern because they are highly infectious and relatively easy to produce.
      Although dispersion might be difficult, the risk is magnified by the fact that
      large populations are susceptible to these agents and only limited treatment and
      vaccination strategies exist. Although the risk of large-scale bioterrorism using
      viral agents is small, public health programs and health care providers must be
      prepared for this potentially devastating impact on public health.

PMID- 12074487
TI  - Microbiological, biological, and chemical weapons of warfare and terrorism.
AB  - Microbiological, biological, and chemical toxins have been employed in warfare
      and in terrorist attacks. In this era, it is imperative that health care
      providers are familiar with illnesses caused by these agents. Botulinum toxin
      produces a descending flaccid paralysis. Staphylococcal enterotoxin B produces a
      syndrome of fever, nausea, and diarrhea and may produce a pulmonary syndrome if
      aerosolized. Clostridium perfringens epsilon-toxin could possibly be aerosolized
      to produce acute pulmonary edema. Ricin intoxication can manifest as
      gastrointestinal hemorrhage after ingestion, severe muscle necrosis after
      intramuscular injection, and acute pulmonary disease after inhalation. Nerve
      agents inhibit acetylcholinesterase and thus produce symptoms of increased
      cholinergic activity. Ammonia, chlorine, vinyl chloride, phosgene, sulfur
      dioxide, and nitrogen dioxide, tear gas, and zinc chloride primarily injure the
      upper respiratory tract and the lungs. Sulfur mustard (and nitrogen mustard) are
      vesicant and alkylating agents. Cyanide poisoning ranges from sudden-onset
      headache and drowsiness to severe hypoxemia, cardiovascular collapse, and death.
      Health care providers should be familiar with the medical consequences of toxin
      exposure, and understand the pathophysiology and management of resulting illness.

PMID- 12074488
TI  - Nuclear terrorism.
AB  - Recent events have heightened awareness of the potential for terrorist attacks
      employing nonconventional weaponry such as biological agents and radiation.
      Historically, the philosophy of nuclear risk has focused on global or strategic
      nuclear exchanges and the resulting damage from large-scale releases. Currently,
      nuclear accidents or terrorist attacks involving low-level or regional release of
      radiation are considered the most likely events. Thus far, there have been
      several regional radiation incidents exposing hundreds of thousands of people to
      radiation, but there have been only a limited number of significant
      contaminations resulting in death. There are several different types of
      radioactive particles that differ in mass, extent of radiation emitted, and the
      degree to which tissue penetration occurs. Radiation affects its toxicity on
      biological systems by ionization, which creates tissue damage by the generation
      of free radicals, disruption of chemical bonds, and directly damaging cellular
      DNA and enzymes. The extent of damage depends on the type of radioisotope and the
      radiation dose. Radiation doses exceeding 2 to 10 Gy are considered lethal.
      Optimal management of radiation casualties requires knowledge of the type and
      dose of radiation received, a recognition of the manifestations of radiation
      sickness, and the use of standard medical care, decontamination, and
      decorporation techniques.

PMID- 12074489
TI  - Unconventional biological threats and the molecular biological response to
      biological threats.
AB  - This article concludes this symposium on potential agents of warfare and
      terrorism with discussion of 3 topics. First, influenza A virus is discussed as a
      potential biological weapon. Although it does not receive much attention in this
      role, the potential for mass casualties and public panic certainly exist if an
      epidemic of a virulent influenza A virus were initiated. Second, agroterrorism,
      terrorism directed at livestock or poultry or crops, is briefly discussed.
      Finally, the potential role of techniques of modern molecular biology to create
      new agents for bioterrorism or enhance the terrorist potential of available
      agents, and the known roles of these techniques in defense against biological
      warfare or terrorism are discussed.

PMID- 12074490
TI  - Application of the scatter diagram technique to the scanning electron microscope:
      preliminary results from diamond.
AB  - Using primary beam energies E0 ranging from 0.2 to 15 keV and an in-lens
      detector, a series of images of the same region of an artificial microstructured
      diamond sample have been acquired in scanning electron microscopy. Next, the
      images were analysed by using a scatter diagram technique to underline the
      topographic contrast change and contrast reversal. The results obtained from 0.5
      to 15 keV are discussed with the help of an expression derived from the constant
      loss model for the secondary electron yield delta of diamond, but including the
      respective roles of the angle of incidence, i, and of the angle of detection,
      alpha. More surprising is the quality of images obtained at a beam energy as low
      as 0.2 keV, and more difficult to explain is the significant contrast change
      between 0.2 keV and 0.5 keV. For the first time, scatter diagrams are used as a
      diagnostic tool in scanning electron microscopy, and after some improvements it
      is hoped that the experimental approach followed here may lead to quantitative
      estimates of the local tilts of a specimen surface.

PMID- 12074491
TI  - Guiding self-assembly with the tip of an atomic force microscope.
AB  - We report the guided self-assembly of nanoparticles to geometrically well-defined
      charge patterns written on a dielectric surface with the conductive tip of an
      atomic force microscope (AFM). Charges are deposited in 30-90-nm thick
      fluorocarbon layers by applying voltage pulses to the conductive AFM tip. The
      samples are being developed by dipping them into an organic suspension of silica
      nanoparticles. Coulomb forces draw the nanoparticles to the charge patterns. With
      this simple process, we achieve a resolution of about 800 nm.

PMID- 12074492
TI  - Tracers in vascular casting resins enhance backscattering brightness.
AB  - Studying cast microvasculature with scanning electron microscopy has expanded our
      knowledge of many circulations, but need arises to determine the blood source of
      vascular beds that are supplied by two circulations. One way to do this is to
      mark the casting resin by adding a tracer compound that can be detected in the
      scanning electron microscope. A potential method of distinguishing different
      substances is to detect the backscattered electrons that are emitted from the
      tracer if the tracer is a heavier element, because heavier elements backscatter
      more electrons. To explore different tracers, we tested lead, titanium, iron,
      osmium, and uranium as solutions of different polarity and powders. The tracers
      were added to 1 ml of methyl methacrylate in log concentrations. Shrinkage,
      hardness, cast quality, and change in brightness from the tracer were compared
      with multivariate analysis at scanning electron microscopic working distances of
      15 and 39 mm on carbon-coated and uncoated specimens. Several concentrations
      caused sedimentation of the tracer and prevented the resin from solidifying.
      Tetraethyl lead shortened the hardening time: uranyl acetate and osmium tetroxide
      prolonged it. Most tracers decreased shrinkage. When lead citrate and Reynolds
      solutions were removed, the brightness correlated with increasing atomic number,
      concentration of the tracer, and mean atomic number of the specimen (p <0.0001).
      The substances that increased contrast most were tetraethyl lead and uranium.
      Backscattering electron detection can distinguish methacrylate casts that have
      small amounts of heavier elements added to them, but an optimal tracer has not
      yet been established.

PMID- 12074493
TI  - Computer modeling of three-dimensional reconstruction algorithm of
      cathodoluminescence material properties, analysis of errors, and optimization of
      variable parameters.
AB  - Three-dimensional (3-D) reconstruction of cathodoluminescence (CL) properties of
      materials (Saparin et al. 1997) is a new nondestructive technique that measures
      quantum yield information of subsurface layers as a set of two-dimensional image
      sections. This technique is able to synthesize a 3-D image without destroying the
      sample. The basis for this technique is the fact that the electrons in scanning
      electron microscopy penetrate the sample at different depths with a variation of
      accelerating voltage. The detected CL emission integrates the information from
      the full volume occupied by the charge carriers. Estimating the errors that occur
      during the reconstruction process is complex since these errors are caused by
      necessary approximations, noise, and the imperfection of the 3-D reconstruction
      algorithm that is employed. An analysis of the factors that affect the accuracy
      of the technique has been made. The estimation of systematic errors and the
      optimization of variable parameters were calculated by computer modeling.

PMID- 12074494
TI  - Direct assessment of recombination noise in semiconductors using electron beam
      induced conductivity.
AB  - The level of internal noise of the transistors, diodes, and other semiconductor
      components limits the successful design of any low noise electronic system. All
      types of noise, namely, Johnson, 1/f, and so forth, are generated due to activity
      of crystalline defects such as vacancies, dislocations, and others. The intensity
      of the electron scattering and recombination processes, inflicted by defects
      (traps), controls the level of noise. Dependent on the dynamic operation
      condition of semiconductor devices, such as external biases and level of current
      injection, the traps will generate certain type and level of noise. Material
      growth or device processing technologies could introduce all kind of defects.
      Therefore, characterization of the semiconductor wafer in the early stages of
      processing (at least before packaging) could help to predict the level of noise
      due to the type and density of defects present on the wafer. Sorting out bad
      semiconductor chips could save money and effort in the radio frequency design of
      low-noise circuits. This current study focuses on 1/f noise modeling, which
      involves most powerful generators of noise and linear defects, named
      dislocations. The study also examines the possibility of assessing this noise by
      quantitative electron beam-induced conductivity (EBIC) measurements. These
      defects could be found in the bulk as well as at the epitaxial interfaces of a
      semiconductor device. The nanoscale size of these defects makes the scanning
      electron beam an instrument of choice for the proposed study. Conventional EBIC
      produces images of the defects, where contrast is proportional to the
      recombination rate at the site of a defect. Since contrast is measured as a
      fraction of one percent, the relative nature of contract value precludes
      quantitative measurements of the recombination rate, thus making quantitative
      assessment of 1/f noise impossible. In our model, using the Boltzman continuity
      equation, the recombination-generation processes per unit of length of a
      dislocation was defined for two operational conditions of EBIC, namely, for low
      and high intensity of an electron beam. The experimental technique of the
      quantitative measurement of carrier recombination (Mil'shtein 2001) consists of
      taking two EBIC scans along the selected defect at two different beam
      intensities, digitally subtracting the first scan from the second one and
      normalizing the result to the size of the electron range. The value of the
      recombination rate, extracted from the model, could then be used to predict the
      level of 1/f noise in the tested semiconductor sample.

PMID- 12074495
TI  - Investigation of unusual inactivity of industrial platinum-rhodium catalyst
      gauze.
AB  - The aim of this work was to obtain information about the causes of unusual lack
      of activation of fresh, unused, 90% platinum-10% rhodium catalyst gauze that was
      detected after the activation process in an industrial ammonia oxidation plant.
      To reach the usual efficiency, it was necessary to regenerate the catalyst
      immediately after the activation procedure by using an acid bath. To avoid future
      unexpected shutdowns in the ammonia oxidation plant, the possible sources of
      impurities accumulated on the catalyst surface were investigated by an analysis
      of the experimental results and technological processes. The absence of
      accumulation on the unused catalyst surface eliminates the possibility of
      contamination during the preparation, while the composition of the impurities
      indicates that it cannot result from the reactor construction material. In mixed
      feedstock, detectable amounts of the poisons mentioned were not detected either
      after filtration or before the reactor. All these considerations imply that the
      time when the catalyst contamination occurred must have been before the contact
      with the gas mixture. From data obtained, it is hypothesized that the origin of
      this substance is from the polluted air in the industrial area where the ammonia
      oxidation plant is located and that the accumulation probably took place during
      the preparation of the catalyst pad.

PMID- 12074496
TI  - Error rates in dental microwear quantification using scanning electron
      microscopy.
AB  - There is a degree of correlation between dietary habits and dental microwear in
      extant primates, and this has enabled inferences to be made about prehistoric
      diets. Several techniques have been used to quantify microwear, but the
      comparability of results derived from each has not been demonstrated. Moreover,
      neither intra- nor interobserver error rates in microwear quantification have
      been documented to date. We here assess intra- and interobserver error using
      Microware 4.0, and evaluate intertechnique comparability using the three methods
      that have been most widely employed in the field. This study documents an overall
      intraobserver error rate of about 7%, and an overall interobserver error rate of
      some 9%. Both intra- and interobserver error appears to be influenced
      substantially by the nature of the micrograph being measured. In no instance did
      the results obtained by different observers using Microware 4.0 differ
      significantly, and there was a reasonable degree of interobserver consistency in
      the rank ordering of micrographs in relation to any given parameter. The results
      obtained through the use of different quantitative techniques differed
      significantly, with an overall intertechnique error rate of approximately 19%.
      Several variables, including differences in magnification factor, scanning
      electron microscope kV settings, and specimen-detector relationships undoubtedly
      contribute to the differences among the three methods, but we were not able to
      assess their relative importance. Microwear quantification permits distinctions
      between broad dietary categories, but the margin of intra- and interobserver
      error should be taken into account when defining pattern differences between
      populations (or species) or when documenting seasonally mitigated differences
      within a taxon. In view of the error introduced by the use of different methods,
      we suggest that a consistent technique, such as offered by the Microware software
      package, be adopted by current researchers to establish a common microwear
      database.

PMID- 12074497
TI  - Scanning tunneling microscope spectroscopy of polymers.
AB  - This paper presents theoretical results on the relationship between density of
      states (DOS) and scanning tunneling microscope current-voltage curves in
      polymers. We considered samples of linear hydrocarbons electrically grounded at
      one of their extremes. The other extreme is electrically connected to the
      microscope tip via electron tunneling through vacuum. When a voltage, V, is
      applied to the tip, electric current, I, flows in the tip-sample circuit. This
      current varies as the voltage varies and depends on the DOS to the extent that no
      current would flow if no electron states exist at a certain energy (or voltage).
      The detailed relationship between DOS and the current-voltage (I-V) curve is not
      known a priori. We solve the corresponding quantum problem in the context of
      tight binding and find that I-V reproduces accurately the resonant energy peaks
      of the DOS. We apply the results to 100 atom-long alkane and alkene chains and
      found that there is a significant voltage shift in the corresponding curves as to
      discriminate one structure from the other.

PMID- 12074498
TI  - Dual effect of first full term pregnancy on breast cancer risk: empirical
      evidence and postulated underlying biology.

PMID- 12074499
TI  - Transient increase in breast cancer risk after giving birth: postpartum period
      with the highest risk (Sweden).
AB  - OBJECTIVE: Identify time-points when the elevated postpartum maternal breast
      cancer risk peaks. METHODS: A case-control study nested within the Swedish
      Fertility Register included 34,018 breast cancer cases from the Swedish Cancer
      Register between 1961 and 1995. From the Fertility Register, 170,001 eligible
      subjects matched to the cases by age were selected as controls. Analysis
      contrasted risk between uniparous (7084 cases and 31,703 controls) and
      nulliparous (5411 cases and 22,580 controls) women and between biparous (13,239
      cases and 65,858 controls) and uniparous women. Logistic regression analysis
      included indicator variables representing each year of age, ages at delivery, and
      time since delivery. RESULTS: Comparing uniparous with nulliparous women the
      transient increase in maternal breast cancer risk peaked 5 years following
      delivery (odds ratio= 1.49, 95% confidence interval 1.01-2.20) and leveled off 15
      years postpartum. Biparous women had a transient increase in risk that was lower
      at its peak than that of uniparous women, occurring about 3 years following
      second delivery. CONCLUSIONS: A time window of 5 years postpartum when maternal
      breast cancer risk is highest was observed. Establishing timing of peak transient
      increase in postpartum breast cancer risk may define the latent period required
      for pregnancy hormones in promoting progression of breast cells that have
      undergone early stages of malignant transformation.

PMID- 12074500
TI  - Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in
      northern and southern Sweden.
AB  - OBJECTIVE: To examine the possible relationships of breast cancer risk to
      prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and
      IGF-binding proteins -1, -2, and -3. METHODS: Within two prospective cohorts in
      Umea and Malmo we measured plasma concentrations of insulin, IGF-I, and IGFBPs
      for a total of 513 incident breast cancer cases and 987 matched controls.
      RESULTS: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I
      adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at
      blood donation, an increase in risk was observed for increasing levels of IGF-I
      in women aged 55 or older, in the Umea cohort only (odds ratios of 1.00, 1.73,
      1.76, 1.90; Ptrend = 0.05). This effect weakened, however, when the analysis was
      restricted to subjects who did not use exogenous hormones for the treatment of
      menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in
      younger women, recruited before age 50, contrary to observations from previous
      studies. In a subcohort where blood samples had been collected after at least
      four hours of fasting, breast cancer risk showed no clear associations with
      levels of insulin, IGFBP-1, or IGFBP-2. CONCLUSIONS: Our results do not confirm
      earlier findings of an association of plasma IGF-I levels with breast cancer risk
      especially in young women, but suggest a possible association with postmenopausal
      breast cancer risk, possibly among ERT/HRT users only. Our results do not support
      the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-I
      and IGFBP-2, are associated with increased breast cancer risk.

PMID- 12074501
TI  - Cancer incidence in California flight attendants (United States).
AB  - OBJECTIVE: To examine unusual exposure opportunities to flight crews from
      chemicals, cosmic radiation, and electric and magnetic fields. METHODS: This
      project evaluated the incidence of cancers of the breast and other sites among
      Association of Flight Attendants (AFA) members residing in California. AFA
      membership files were matched to California's statewide cancer registry to
      identify a total of 129 newly diagnosed invasive cancers among AFA members with
      California residential histories between 1988 and 1995. RESULTS: Compared to the
      general population, female breast cancer incidence was over 30% higher than
      expected, and malignant melanoma incidence was roughly twice that expected. Both
      of these are cancers that are associated with higher socioeconomic status and
      have been suggestively associated with various sources of radiation. CONCLUSIONS:
      Consistent with the results from Nordic studies of cabin crews and a recent meta
      analysis of prior studies, these data suggest that follow-up investigations
      should focus on the potential relative contribution of workplace exposures and
      lifestyle characteristics to the higher rates of disease for these two cancers.

PMID- 12074502
TI  - Body mass index, height, and postmenopausal breast cancer mortality in a
      prospective cohort of US women.
AB  - OBJECTIVE: Epidemiologic evidence suggests a positive association between body
      mass, adult height, and postmenopausal breast cancer. However, most studies have
      not been large enough to examine the association across a very wide range of body
      mass or height, and few studies have assessed the relationship between body mass
      or height and postmenopausal breast cancer mortality. METHODS: The relation
      between body mass index (BMI) and height and postmenopausal breast cancer
      mortality was examined in the American Cancer Society's Cancer Prevention Study
      II (CPS-II), a large prospective mortality study of US adults enrolled in 1982.
      After 14 years of follow-up, 2852 breast cancer deaths were observed among
      424,168 postmenopausal women who were cancer-free at interview. Cox proportional
      hazards modeling was used to estimate relative risks and to control for potential
      confounding. RESULTS: Breast cancer mortality rates increased continually and
      substantially with increasing BMI (rate ratio (RR) = 3.08, 95% confidence
      interval (CI) = 2.09-4.51 for BMI > 40.0 compared to BMI 18.5-20.49). If causal,
      the multivariate-adjusted RR estimates in this study correspond to approximately
      30-50% of breast cancer deaths among postmenopausal women in the US population
      being attributable to overweight. Breast cancer mortality also increased with
      increasing height up to 66 inches with RR= 1.64, (95% CI = 1.23-2.18) in women 66
      inches tall compared to those <60 inches. CONCLUSIONS: Postmenopausal obesity is
      an important and potentially avoidable predictor of fatal breast cancer in this
      study. These results underscore the importance of maintaining moderate weight
      throughout adult life.

PMID- 12074503
TI  - Association of correlates of endogenous hormonal exposure with breast cancer risk
      in 426 families (United States).
AB  - OBJECTIVE: Women with a strong family history of breast cancer are at
      significantly increased risk of developing the disease. There is emerging
      evidence that certain reproductive factors may further elevate risk in these
      women. We examined whether a family history of breast cancer modifies the
      association between correlates of endogenous hormonal exposures and breast cancer
      in a study of 426 families ascertained through breast cancer probands. METHODS:
      Analyses of reproductive factors and breast cancer were performed on 395 sisters
      and daughters of probands, 3014 nieces and granddaughters. and 2768 marry-ins.
      RESULTS: Through 226,266 person-years of follow-up since 1952, 240 women
      developed breast cancer. No statistically significant interactions were observed
      between relationship to proband and age at menarche, age at menopause, other
      characteristics of the menstrual cycle, parity, age at first and last birth,
      infertility, and total ovulatory years. CONCLUSIONS: Our findings suggest that
      most reproductive factors influence breast cancer risk similarly in women with
      and without a family history of breast cancer. Further studies are needed on
      individuals who are more homogeneous with regard to hereditary background.
      However, other options for prevention, such as prophylactic surgery or
      chemoprevention, may be necessary to have a substantial impact on risk reduction
      in women at high genetic risk.

PMID- 12074504
TI  - Breast self-examination: who teaches it, who is taught, and how often? (United
      States).
AB  - BACKGROUND: Although the effectiveness of breast self-examination (BSE) has not
      been established, it is widely practiced and taught. However, it is not clear
      which patients and providers are involved in BSE teaching, nor how often it
      occurs. We undertook this study at a large New England Health Maintenance
      Organization (HMO) to answer these questions. METHODS: The study was a
      retrospective cohort of 2242 randomly selected women aged 40-69 with no history
      of breast cancer and at least one screening clinical breast examination, followed
      over a ten-year period, including their medical providers (n = 356). Data were
      collected via computerized medical records. RESULTS: Sixty-eight percent of women
      had documented BSE teaching at least once in the ten years, increasing from 13%
      taught in 1983 to 36% in 1993 (p = 0.001). Teaching was related to younger age,
      increasing numbers of clinical breast examinations, screening mammograms, and
      prior BSE teachings. Patient race, income, family history of breast cancer, and
      estrogen replacement use were not related to teaching. Sixty-one percent of all
      providers taught BSE at least once during the ten years. Internists (OR 6.37, 95%
      CI 2.23-17.3) and non-physician providers (OR 12.8, 95% CI 3.0-54.4) were more
      likely to teach at least half of their patients than were obstetrician
      gynecologists. Recent medical school graduates taught BSE more often. Provider
      gender was not associated with teaching. CONCLUSIONS: Over two-thirds of women
      patients in this HMO setting were taught BSE and the majority of providers taught
      BSE at least once during the ten years. Rates of teaching tripled over the
      decade. It is important to establish the effectiveness of BSE and its appropriate
      role in breast cancer screening.

PMID- 12074505
TI  - Lifestyle and nutritional determinants of bioavailable androgens and related
      hormones in British men.
AB  - OBJECTIVE: To investigate the lifestyle and nutritional determinants of serum
      bioavailable androgens and their related hormones in men. METHODS: This study is
      based on a sample of 696 men with a wide range of nutrient intakes, whose diet
      and lifestyle characteristics were assessed with a questionnaire and serum sex
      hormones measured using immunoassays. RESULTS: Men aged 70 years or older had 12%
      lower testosterone and 40% lower free-testosterone (FT) and androstanediol
      glucuronide (A-diol-g) concentrations than men who were 20-29 years of age.
      Conversely, sex hormone-binding globulin (SHBG) and luteinizing hormone (LH)
      concentrations were 90% and 49% higher in the oldest age group compared with the
      lowest, respectively. Men who had a body mass index (BMI) of 30+ kg/m2 had 30%
      lower testosterone, 45% lower SHBG, 22% lower LH and 5% lower FT concentrations
      compared with men with a BMI of <20 kg/m2. Conversely, A-diol-g concentration was
      15% higher in the highest BMI category compared with the lowest. A high waist
      circumference was further associated with a 12% lower testosterone and SHBG
      concentration, after adjusting for BMI. Compared with never-smokers, smoking 10+
      cigarettes/day was associated with 15% higher testosterone, 22% higher SHBG and
      17% higher LH concentrations; FT and A-diol-g were not associated with smoking.
      Compared with no exercise, vigorous exercise of 3+ hours/week was associated with
      11% higher testosterone and 16% higher SHBG concentrations, whilst LH, FT, and A
      diol-g were not associated with vigorous exercise. Dietary factors were not
      strongly associated with hormones, although saturated fat intake was negatively
      associated with SHBG (r = -0.10; p = 0.01) and alcohol intake was positively
      associated with A-diol-g (r = 0.11; p = 0.004). No dietary factors were
      associated with testosterone, FT, or LH. CONCLUSIONS: Age is the strongest
      determinant of serum bioavailable androgens. BMI and some lifestyle and dietary
      factors influence SHBG and testosterone concentrations, but have no strong
      association with FT, suggesting that homeostasis is effective. A-diol-g shows
      broadly similar associations to FT, with the exception of the effect of BMI and
      alcohol.

PMID- 12074506
TI  - Risk factors for medullary thyroid carcinoma: a pooled analysis.
AB  - OBJECTIVE: To investigate risk factors for medullary thyroid cancer (MTC).
      METHODS: We conducted a pooled analysis of 14 case-control studies from Europe,
      North America, and Asia, including 67 medullary cancers (43 women and 24 men)
      diagnosed in ten studies. Of the original 4776, we selected five controls per
      case matched on study, gender, and age. The pooled odds ratios (OR) were
      estimated using conditional logistic regression. RESULTS: Education, weight, and
      body mass were not associated with MTC, but a significant positive relationship
      was seen with height (OR = 2.6 for highest vs lowest tertile). Significant excess
      risks were associated with a history of thyroid nodules (OR = 12), hypertension
      (OR = 2.3), gallbladder disease (OR = 4.3), and allergies (OR = 2.2). Among
      current smokers, a decreased risk of MTC was observed with increasing number of
      cigarettes. The risk was significantly elevated among women having a first birth
      after age 25 years, but no clear pattern emerged for other reproductive factors.
      CONCLUSIONS: Although the number of MTC was small, we detected several
      significant associations, including prior thyroid and other diseases.

PMID- 12074507
TI  - Dietary catechins and cancer incidence among postmenopausal women: the Iowa
      Women's Health Study (United States).
AB  - OBJECTIVE: Catechins are bioactive flavonoids present in tea, fruits, and
      vegetables. Previous epidemiological studies regarding tea and cancer risk were
      inconclusive, possibly because catechins are also present in other plant foods.
      We investigated whether a high intake of catechins are associated with cancer
      incidence among postmenopausal women. METHODS: A cohort of 34,651 postmenopausal
      cancer-free women aged 55-69 years were followed from 1986 to 1998. At baseline,
      data on diet, medical history, and lifestyle were collected. Incident cancers
      were obtained through linkage with a cancer registry. Cox proportional hazards
      analysis was used to estimate risk ratios. RESULTS: After adjustment for
      potential confounders, catechin intake was inversely associated with rectal
      cancer incidence only (risk ratios from lowest to highest quartile: 1.00, 0.93,
      0.73, and 0.55; p for trend 0.02). Non-significant inverse trends were found for
      cancer of the upper digestive tract, pancreas, and for hematopoietic cancers.
      Catechins derived primarily from fruits, (+)-catechin and (-)-epicatechin, tended
      to be inversely associated with upper digestive tract cancer, whereas catechins
      derived from tea were inversely associated with rectal cancer. CONCLUSIONS: Among
      several cancers studied, our data suggest that catechin intake may protect
      against rectal cancer. The distinct effects found for catechins derived from
      solid foods (fruits) and beverages (tea) may be due to differences in
      bioavailability or metabolism of the catechins, or to their interactions with
      other dietary components.

PMID- 12074508
TI  - Meat consumption, cigarette smoking, and genetic susceptibility in the etiology
      of colorectal cancer: results from a Dutch prospective study.
AB  - OBJECTIVE: We evaluated the effect of meat consumption and cigarette smoking in
      combination with N-acetyltransferases 1 and 2 (NAT1 and NAT2), and glutathione S
      transferase M1 (GSTM1) genotypes on colorectal cancer. METHODS: From a Dutch
      prospective study, after 8.5 years of follow-up, data of 102 incident colorectal
      cancer cases and a random sample of 537 controls frequency-matched for gender and
      age were analyzed. Baseline information on dietary and smoking habits, as well as
      blood samples for DNA isolation and genotyping, were available. RESULTS: Red meat
      intake increased colorectal cancer risk among men (OR 2.7; 95% CI 1.1-6.7 highest
      vs. lowest intake), whereas poultry and fish decreased risk among women (OR 0.5;
      95% CI 0.2-1.07). Cigarette smoking for at least 16 years increased colorectal
      cancer risk among former smokers only (OR 2.7; 95% CI 1.0-7.4), compared to those
      having smoked for 15 years or less. NAT1 and NAT2 polymorphisms did not
      significantly modify these associations. High consumption of poultry and fish was
      inversely associated with colorectal cancer only in the presence of GSTM1.
      CONCLUSIONS: In this study meat consumption and former long-term smoking were
      associated with colorectal cancer. Associations of colorectal cancer with
      different types of meat were modified by gender and GSTM1 genotype.

PMID- 12074509
TI  - Effects of a finite outer scale on the measurement of atmospheric-turbulence
      statistics with a Hartmann wave-front sensor.
AB  - Phase-structure and aperture-averaged slope-correlated functions with a finite
      outer scale are derived based on the Taylor hypothesis and a generalized
      spectrum, such as the von Karman modal. The effects of the finite outer scale on
      measuring and determining the character of atmospheric-turbulence statistics are
      shown especially for an approximately 4-m class telescope and subaperture. The
      phase structure function and atmospheric coherent length based on the Kolmogorov
      model are approximations of the formalism we have derived. The analysis shows
      that it cannot be determined whether the deviation from the power-law parameter
      of Kolmogorov turbulence is caused by real variations of the spectrum or by the
      effect of the finite outer scale.

PMID- 12074510
TI  - Optimal suppression of quantization noise with pseudoperiodic multilevel phase
      gratings.
AB  - A comprehensive two-step approach to design staircase-type multilevel diffractive
      phase elements (DPEs) that generate arbitrary desired diffraction patterns with
      the highest possible accuracy is presented. First a preliminary periodic grating
      with an unconstrained phase delay and an optimized nonuniform amplitude profile
      is designed by means of a customized iterative Fourier-transform algorithm. Then
      this preliminary grating is subjected to a phase quantization in which strict
      periodicity is forgone in favour of the best possible preservation of the shape
      of the power spectrum yielding a final phase only DPE with only rudimentary
      periodicity. An arbitrarily high similarity between the diffraction patterns of
      the final DPE and the preliminary grating can be achieved independently of the
      number D of discrete phase delay levels as long as D > or = 3. The signal-to
      noise ratio of the final DPE is close to the theoretical upper limit. These
      properties are confirmed in computer simulations and demonstrated in optical
      experiments. Pseudoperiodic DPEs may have applications in optical computing,
      optical communication and networking, optical authentication, or coherent laser
      coupling.

PMID- 12074511
TI  - Direct deflection method for determining refractive-index profiles of polymer
      optical fiber preforms.
AB  - We present a method for determining the refractive-index profile of polymer
      optical fiber preforms through a direct-deflection measurement. The method is
      simple to use, compact, and has good resolution. The profile is obtained from the
      deflection data by numerically integrating the differential-ray equation for a
      radial refractive-index gradient. Corrections for topographical deviations are
      also discussed. Results for both graded-index and step-index fibers are
      presented.

PMID- 12074512
TI  - Birefringent filter synthesis by use of a digital filter design algorithm.
AB  - We present an efficient method for designing birefringent filters comprising a
      number of birefringent sections with equal length and arbitrary orientation
      between two polarizers and for producing a specified spectral response in
      transmission. The method uses a digital filter design algorithm (i.e., the Remez
      algorithm) to determine an optimal polynomial approximation to obtain a specified
      finite impulse response, and a layer-peeling algorithm to calculate the filter
      structure parameters. The design procedure is demonstrated for a 14-section
      bandpass filter with sidelobes below -40 dB. The influence of errors in length
      and orientation of the birefringent sections on the filter's spectral response is
      also discussed.

PMID- 12074513
TI  - One-way imaging through a polarization-sensitive aberrator by use of an optical
      lock-in detection.
AB  - We demonstrate one-way image compensation for a thin and polarization-sensitive
      aberrator by the use of optical lock-in detection. Optical lock-in detection is
      accomplished by dual-phase modulation in four-wave mixing in a holographic
      medium. In our scheme, both the image-bearing beam and the reference beam
      copropagate through the aberrator under the same polarization condition. The
      holographic grating that reconstructs only the corrected image was generated by
      selective recording in optical lock-in detection. The phase aberration is
      subtracted out in the holographic process. This scheme permits image correction
      through the polarization-sensitive aberrator.

PMID- 12074515
TI  - Double-phase holograms implemented with phase-only spatial light modulators:
      performance evaluation and improvement.
AB  - We propose modified hologram cells (or macropixels) for the computer-generated
      double-phase holograms (DPHs), based on pixelated phase-only spatial light
      modulators (SLMs). Such modified DPHs exhibit a substantially improved signal-to
      noise ratio, in comparison with the conventional ones. The modified macropixels
      are formed by arrays of either 1 x 2 or 2 x 2 SLM pixels.

PMID- 12074514
TI  - Characterization of dupont photopolymer: determination of kinetic parameters in a
      diffusion model.
AB  - We investigate the recording dynamics of Omnidex photopolymer film from DuPont.
      We use a reviewed version of the diffusion model proposed by Zhao and Mouroulis
      [J. Mod. Opt. 41, 1929 (1994)] in order to describe the recording response that
      combined photopolymerization and free-monomer diffusion process. Two different
      experiments are detailed that lead to the determination of material kinetic
      parameters. These values are introduced in the numerical model to provide
      quantitative simulations of a grating formation under various holographic
      exposures. Theoretical results are experimentally checked as a validation of the
      model. We extend its applications to several secondary investigations, such as
      volume-shrinkage influence on refractive-index distribution and spectral
      selectivity of reflection gratings. This study improves the understanding of the
      recording process and consequently allows to build more accurate holographic
      components in this material to be built.

PMID- 12074516
TI  - Obtaining the phase of an interferogram by use of an evolution strategy: part I.
AB  - We present a method for obtaining the phase of a noisy simulated interferogram.
      We find the wave-front aberrations by transforming the problem of fitting a
      polynomial into an optimization problem, which is then solved using an
      evolutionary algorithm. Our experimental results show that our method yields a
      more accurate solution than other methods commonly used to solve this problem.

PMID- 12074517
TI  - Reduction of the correlation sensitivity to the changes of the input illumination
      by a post processing based on the correlation statistics.
AB  - Linear-correlation amplitude changes when the intensity level of the input image
      is modified. As recognition is often based on the correlation-peak level, a
      change of the input illumination may result in a false recognition. We propose an
      illumination-change compensation by a post processing of the correlation
      distribution that is based on statistical measures of the correlation histograms.
      The theoretical background and simulation results are provided in the frame of an
      actual application in biology.

PMID- 12074518
TI  - Improved method for isochromatic demodulation by RGB calibration.
AB  - The red-blue-green (RGB) calibration technique consists in constructing an a
      priori calibration table of the isochromatic retardation versus the triplet of
      RGB values obtained with a RGB CCD camera. In this way a lookup table (LUT) is
      built in which the entry is the corresponding RGB triplet and the output is the
      given retardation. This calibration (a radiometric quantity) depends on the
      geometric and chromatic parameters of the setup. Once the calibration is
      performed, the isochromatic retardation at a given point of the sample is
      computed as the one that minimizes the Euclidean distance between the measured
      RGB triplet and the triplets stored in the LUT. We present an enhanced RGB
      calibration algorithm for isochromatic fringe pattern demodulation. We have
      improved the standard demodulation algorithm used in RGB calibration by changing
      the Euclidean cost function to a regularized one in which the fidelity term
      corresponds to the Euclidean distance between RGB triplets; the regularizing term
      forces piecewise continuity for the isochromatic retardation. Additionally we
      have implemented a selective search in the RGB calibration LUT. We have tested
      the algorithm with simulated as well as real photoelastic data with good results.

PMID- 12074519
TI  - Design of microchannel free-space optical interconnects based on vertical-cavity
      surface-emitting laser arrays.
AB  - We investigate the design of free-space optical interconnects (FSOIs) based on
      arrays of vertical-cavity surface-emitting lasers (VCSELs), microlenses, and
      photodetectors. We explain the effect of the modal structure of a multimode VCSEL
      beam on the performance of a FSOI with microchannel architecture. A Gaussian-beam
      diffraction model is used in combination with the experimentally obtained
      spectrally resolved VCSEL beam profiles to determine the optical channel
      crosstalk and the signal-to-noise ratio (SNR) in the system. The dependence of
      the SNR on the feature parameters of a FSOI is investigated. We found that the
      presence of higher-order modes reduces the SNR and the maximum feasible
      interconnect distance. We also found that the positioning of a VCSEL array
      relative to the transmitter microlens has a significant impact on the SNR and the
      maximum feasible interconnect distance. Our analysis shows that the departure
      from the traditional confocal system yields several advantages including the
      extended interconnect distance and/or improved SNR. The results show that FSOIs
      based on multimode VCSELs can be efficiently utilized in both chip-level and
      board-level interconnects.

PMID- 12074520
TI  - Partial-response signaling for phase-change optical data storage without
      electronic equalization.
AB  - We describe the application of partial-response (PR) signaling in rewritable
      phase-change optical data storage. No electronic filter is necessary to shape the
      readout signal to a certain PR target. A PR-like waveform at the output of the
      read channel is directly achieved by optical recording. A genetic algorithm is
      used to optimize the parameters for writing and therefore to minimize the
      difference between the actual readout signal and the ideal PR waveform. With a
      laser wavelength of 0.66 microm and an objective lens with a numerical aperture
      of 0.6, four linear densities were examined: 0.4, 0.3, 0.25, and 0.2 microm/bit
      (without modulation). Results showed that the linear density of 0.25 microm/bit
      can be realized on a rewritable digital-versatile disk.

PMID- 12074521
TI  - Use of capsaicin cream for abdominal wall scar pain.

PMID- 12074522
TI  - When to begin treatment in patients with elevated TSH levels?

PMID- 12074523
TI  - The care of low back problems: less is more.

PMID- 12074524
TI  - Which interventions help to prevent falls in the elderly?

PMID- 12074525
TI  - Guidelines for managing Alzheimer's disease: part I. Assessment.
AB  - Family physicians play a key role in assessing and managing patients with
      Alzheimer's disease and in linking the families of these patients to supportive
      services within the community. As part of comprehensive management, the family
      physician may be responsible for coordinating assessments of patient function,
      cognition, comorbid medical conditions, disorders of mood and emotion, and
      caregiver status. Suggestions for easily administered and scored assessment tools
      are provided, and practical tips are given for supporting primary caregivers,
      thereby increasing efficiency and quality of care for patients with Alzheimer's
      disease.

PMID- 12074527
TI  - Evaluation of constipation.
AB  - Constipation is the reason for 2.5 million physician visits per year in the
      United States, with more than one half of these visits to primary care
      physicians. Patients and physicians frequently define constipation differently.
      To determine the underlying cause of constipation, it is important to evaluate
      the patient's general health, psychosocial status, medical illnesses, dietary
      fiber intake, and use of constipating medications. The differential diagnosis of
      constipation and the approach to its evaluation differ in adults and children.
      Tests of physiologic function are usually reserved for constipation that does not
      respond to conventional therapy. Family physicians can effectively manage most
      patients who have constipation.

PMID- 12074526
TI  - Corns and calluses resulting from mechanical hyperkeratosis.
AB  - The formation of corns and calluses can be caused by mechanical stresses from
      faulty footgear (the wearing of poorly fitting shoes), abnormal foot mechanics
      (deformity of the foot exerting abnormal pressure), and high levels of activity.
      Corns and calluses result from hyperkeratosis, a normal physiologic response of
      the skin to chronic excessive pressure or friction. Treatment should provide
      symptomatic relief and alleviate the underlying mechanical cause. The lesions
      will usually disappear following the removal of the causative mechanical forces.
      Most lesions can be managed conservatively by the use of properly fitting shoes
      and padding to redistribute mechanical forces. Surgery is only indicated if
      conservative measures fail and should be aimed at correcting the abnormal
      mechanical stresses.

PMID- 12074528
TI  - Information from your family doctor. Constipation in adults.

PMID- 12074529
TI  - Information from your family doctor. Constipation in your child.

PMID- 12074530
TI  - Neuroimaging in low back pain.
AB  - Patients commonly present to family physicians with low back pain. Because the
      majority of patients fully or partially recover within six weeks, imaging studies
      are generally not recommended in the first month of acute low back pain.
      Exceptions include patients with suspected cauda equina syndrome, infection,
      tumor, fracture, or progressive neurologic deficit. Patients who do not improve
      within one month should obtain magnetic resonance imaging if a herniated disc is
      suspected. Computed tomographic scanning is useful in demonstrating osseous
      structures and their relations to the neural canal, and for assessment of
      fractures. Bone scans can be used to determine the extent of metastatic disease
      throughout the skeletal system. All imaging results should be correlated with the
      patient's signs and symptoms because of the high rate of positive imaging
      findings in asymptomatic persons.

PMID- 12074532
TI  - Information from your family doctor. How to prevent heat-related illnesses.

PMID- 12074531
TI  - Evaluation and treatment of heat-related illnesses.
AB  - The body's ability to regulate core temperature depends on both host (internal)
      and environmental (external) factors. Although athletes are commonly thought to
      be most at risk for heat illnesses, children and the elderly are particularly
      vulnerable. Heat cramps, which are caused by fluid and electrolyte imbalances,
      are treated with massage, and fluid and electrolyte replacement. Heat exhaustion
      occurs both as water- and sodium-depleted types, with associated symptoms such as
      malaise, vomiting, and confusion. Treatment involves taking the affected person
      to a cool environment and replacing fluids and electrolytes if needed. In more
      serious cases, intravenous hydration may be necessary, although monitoring of
      serum sodium levels is important to prevent cerebral edema. If not treated
      promptly, heat exhaustion may evolve into heatstroke, a deadly form of heat
      illness. Heatstroke occurs in classic and exertional forms and is present when
      the core body temperature exceeds 40 degrees C (104 degrees F). The patient may
      experience cardiac arrhythmias, rhabdomyolysis, serum chemistry abnormalities,
      disseminated intravascular coagulation, and death. Heatstroke is a medical
      emergency that should be treated immediately with temperature-lowering techniques
      such as immersion in an ice bath or evaporative cooling. Fluid resuscitation is
      important but should be closely monitored, and renal function may need to be
      protected with mannitol and diuretics. It is important to be vigilant for heat
      illnesses because they occur insidiously but progress rapidly.

PMID- 12074533
TI  - Peripheral arterial disease.

PMID- 12074534
TI  - Photo quiz. Foot bumps: now you see them, now you don't.

PMID- 12074536
TI  - Can friends become patients?

PMID- 12074535
TI  - Significant FDA approvals in 2001.

PMID- 12074537
TI  - Evaluation of multicomponent non-viral vectors for liver directed gene delivery.
AB  - Multicomponent, non-viral gene delivery vehicles are designed to have as a
      minimum, a DNA binding component, and a cell recognition component for specific
      delivery to target cells. The DNA binding component cannot only bind, but also
      protect DNA from serum degradation, and tends to condense DNA to sizes that can
      be taken up by receptor-mediated processes of target cells. Generally, cationic
      peptides, single chained, e.g. poly-L-lysine or branched polymers or synthetic
      peptides with DNA binding properties are used for DNA binding components. Ligands
      for binding to receptors on cell surfaces can be covalently linked to the DNA
      binding component. Multicomponent, non-viral vectors have been successfully used
      to deliver genes into cells in vitro and in vivo. Improvements have been made to
      the non-viral carriers resulting in increased solubility of DNA/carrier complexes
      and longer survival in serum. Improvements have also been made by incorporating
      fusogenic/lysosomolytic components that enable DNA/carrier complexes to escape
      intracellular degradation and enhance the levels and duration of expression of
      genes in vitro and in vivo.

PMID- 12074538
TI  - Altered organ accumulation of oligonucleotides using polyethyleneimine grafted
      with poly(ethylene oxide) or pluronic as carriers.
AB  - Passive targeting provides a simple strategy based on natural properties of the
      carriers to deliver DNA molecules to desired compartments. Polyethylenimine (PEI)
      is a potent non-viral system that has been known to deliver efficiently both
      plasmids and oligonucleotides (ODNs) in vitro. However, in vivo systemic
      administration of DNA/PEI complexes has encountered significant difficulties
      because these complexes are toxic and have low biodistribution in target tissues.
      This study evaluates PEI grafted with poly(ethylene oxide) (PEO(8K)-g-PEI(2K))
      and PEI grafted with non-ionic amphiphilic block copolymer, Pluronic P85 (P85-g
      PEI(2K)) as carriers for systemic delivery of ODNs. Following i.v. injection an
      antisense ODN formulated with PEO(8K)-g-PEI(2K) accumulated mainly in kidneys,
      while the same ODN formulated with P85-g-PEI(2K) was found almost exclusively in
      the liver. Furthermore, in the case of the animals injected with the P85-g
      PEI(2K)-based complexes most of the ODN was found in hepatocytes, while only a
      minor portion of ODN was found in the lymphocyte/monocyte populations. The
      results of this study suggest that formulating ODN with PEO(8K)-g-PEI(2K) and P85
      g-PEI(2K) carriers allows targeting of the ODN to the liver or kidneys,
      respectively. The variation in the tissue distribution of ODN observed with the
      two carriers is probably due to the different hydrophilic-lipophilic balance of
      the polyether chains grafted to PEI in these molecules. Therefore, polyether
      grafted PEI carriers provide a simple way to enhance ODN accumulation in a
      desired compartment without the need of a specific targeting moiety.

PMID- 12074539
TI  - In vivo application of non-viral vectors to the liver.
AB  - The liver plays a central role in many inherited and acquired genetic disorders,
      and thus is a potential target for nucleic acid therapies. Despite the great
      strides made in basic molecular biology over the last two decades successful gene
      therapy remains elusive. Most recently, there has been considerable effort to
      develop non-viral gene therapy approaches, in part, to overcome the potential
      complications associated with viral delivery systems. This review outlines the
      different non-viral approaches available to the liver, and includes a detailed
      review of recent advances in delivery vectors for use in techniques such as gene
      augmentation, with particular emphasis on useful applications of antisense and
      ribozyme technology.

PMID- 12074540
TI  - Strategies for hepatic gene correction.
AB  - Gene augmentation has been the paradigm in the majority of gene therapy protocols
      but in recent years the potential of repairing the mutated gene in situ by
      targeted gene correction has become a reality. In fact, targeted gene repair has
      many advantages over conventional replacement strategies, notably the possibility
      to treat dominant as well as recessive disorders, and the small molecular size of
      the pharmacologically active agent. Chimeric RNA/DNA oligonucleotides, small
      fragment homologous replacement, as well as triplex-forming and single-stranded
      oligonucleotides are all examples of the growing armamentarium for gene repair,
      and are the subject of this review. In addition, we have also included a
      discussion of the reawakened Sleeping Beauty (SB) transposon system as a novel
      non-viral gene replacement strategy.

PMID- 12074541
TI  - The development of polyplex-based DNA vaccines.
AB  - DNA immunisation provides new possibilities for the development of effective
      vaccines for the prophylaxis and treatment of several diseases and infections.
      Application of such vaccines for mucosal (secretory or local) vaccination
      provides a powerful means to gain protection against local infection that enters
      and colonises the mucosa whilst inducing concomitant systemic immunity. This
      review examines the current and potential applications for polyplex-based mucosal
      vaccination strategies, notably those aimed at gaining expression of transgenes
      within dendritic cells, in order to gain both T-helper and cytotoxic T cell (CTL)
      responses. Emphasis is given to the development of polyplex-based oral vaccines
      in conjunction with microparticulate systems.

PMID- 12074542
TI  - Overcoming the inflammatory toxicity of cationic gene vectors.
AB  - Cationic lipid- and polymer-based vectors are the most extensively studied
      synthetic gene vectors. These vectors have been widely used in animal models and
      some have been tested in clinical trials. The clinical progress of these vectors
      has been slowed by their inflammatory toxicity. This review summarizes the
      observations, the mechanisms, and various strategies employed to overcome the
      inflammatory toxicity of cationic gene vectors.

PMID- 12074543
TI  - Biocompatibility of polycations: in vitro agglutination and lysis of red blood
      cells and in vivo toxicity.
AB  - The effects of six polycations were studied in vitro on red blood cells (RBC) and
      in vivo after intravenous administration. Hemagglutination and hemolysis depended
      not only on the molar mass and the concentration of these polycations, but also
      on their chemical nature. The hemagglutination and hemolysis induced by poly(L
      lysine), diethylaminoethyldextran, poly(dimethyldiallylammonium) chloride and
      poly[2-(dimethylamino)ethyl methacrylate] was low to moderate, whereas a severe
      hemolysis was induced by a partially quaternized poly[thio-1-(N,N-diethyl
      aminoethyl)ethylene]. In the case of poly(epsilon-lysine), no significant
      hemagglutination nor hemolysis was observed. The presence of plasma proteins
      reduced both agglutination and hemolysis. This protective effect was enhanced
      when the polycations interacted with plasma proteins before contact with RBC. In
      the presence of albumin, the behavior depended on the polycation and on the order
      of addition of the three components of the suspension, namely albumin, polycation
      and RBC. Depending on the polycation, albumin-polycation complexes were either
      less active or more active on RBC than the same polycation in protein-free
      medium. In vivo the studied polycations induced an immediate mortality except
      poly(epsilon-lysine), which induced a delayed mortality. The minimal dose of
      polycations inducing immediate mortality paralleled their effect on RBC.

PMID- 12074544
TI  - Delivering gene therapy.

PMID- 12074545
TI  - Development of long-circulating polyelectrolyte complexes for systemic delivery
      of genes.
AB  - Extended systemic circulation of vectors for gene delivery has long been a goal
      for cancer gene therapy. In recent years, several groups have evaluated the
      feasibility of gaining extended circulation of polyplex vectors by endowing them
      with steric stabilisation, resulting from the presence of a surface layer of
      hydrophilic polymer. Although this approach has been in itself mainly
      unsuccessful, remarkable progress has been gained when steric stabilisation has
      been combined with "lateral stabilisation", using a range of agents to crosslink
      the surface of the complexes. Lateral stabilisation has been achieved using low
      molecular weight crosslinking agents, and also using multivalent polymers
      designed for cooperative surface attachment to the polyplex. In this way plasma
      clearance kinetics can be substantially extended, with a half lives for clearance
      in excess of 90 min. In order to enable transgene expression within target cells
      it can be necessary for the vectors to undergo triggered activation following
      arrival at the target site. The most promising way to achieve this is by
      reductive activation of the vector within the cytoplasm or nucleus of the target
      cell. State of the art in this rapidly progressing field is reviewed.

PMID- 12074546
TI  - Influence of physicochemical properties on pharmacokinetics of non-viral vectors
      for gene delivery.
AB  - The influence of physicochemical properties on the in vivo pharmacokinetics of
      gene delivery vectors after systemic administration is reviewed based on our
      studies. We have been studying the development of DNA delivery systems, such as
      plasmid DNA complexed with cationic polymers (polyplexes) and cationic liposomes
      (lipoplexes). Even if target-recognizable ligand is incorporated into the system,
      the overall physicochemical properties, notably size and charge, are predominant
      factors influencing in vivo disposition characteristics of the vector. Based on
      this consideration, liver cell-specific carrier systems via receptor-mediated
      endocytosis were successfully developed by optimizing physicochemical
      characteristics. In conclusion, rational design of gene delivery vectors requires
      an understanding of their pharmacokinetics in relation to the physicochemical
      properties. Optimization of the physicochemical properties is important for
      successful in vivo gene delivery by non-viral vectors.

PMID- 12074547
TI  - Focus on primary care. Thyroid function and dysfunction in women.
AB  - All forms of thyroid disease are more common in women. The reason for this gender
      predilection has not been entirely elucidated but may relate to the closely
      intertwined relationship between thyroid function and the female reproductive
      axis. Thyroid dysfunction influences both menstrual function and fertility,
      likely through changes in sex hormone levels, gonadotropin release, and possibly
      ovarian function. Similarly, alterations in reproductive physiology can modulate
      thyroid function. In such settings as pregnancy, when sex hormone levels
      fluctuate markedly, variations in thyroid function occur frequently. For the
      clinician, understanding when such alterations require intervention is critical.
      TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING
      OBJECTIVES: After completion of this article, the reader will be able to describe
      the abnormalities of the female reproductive axis associated with both hypo- and
      hyperthyroidism, to summarize how female sex hormones affect thyroid function,
      and to explain the effects of pregnancy on thyroid conditions.

PMID- 12074548
TI  - The cdk5 homologue, crp, regulates endocytosis and secretion in dictyostelium and
      is necessary for optimum growth and differentiation.
AB  - Dictyostelium Crp is a member of the cyclin-dependent kinase (Cdk) family of
      proteins. It is most related in sequence to mammalian Cdk5, which unlike other
      members of the family, has functions that are unrelated to the cell cycle. In
      order to better understand the function of Crp in Dictyostelium, we overexpressed
      a dominant negative form, Crp-D144N, under the control of the actin 15 promoter.
      Cells overexpressing Crp-D144N exhibit a reduced growth rate in suspension
      culture and reduced rates of fluid-phase endocytosis and phagocytosis. There is
      no reduction in Cdc2 kinase activity in extracts from cells overexpressing Crp
      D144N, suggesting that the growth defect is not due to inhibition of Cdc2. In
      addition to the growth defect, the act15::crp-D144N transformants aggregate at a
      slower rate than wild-type cells and form large aggregation streams. These
      eventually break up to form small aggregates and most of these do not produce
      mature fruiting bodies. The aggregation defect is fully reversed in the presence
      of wild-type cells but terminal differentiation is only partially rescued. In
      act15::crp-D144N transformants, the countin component of the counting factor, a
      secreted protein complex that regulates the breakup of streams, mostly appears
      outside the cell as degradation products and the reduced level of the intact
      protein may at least partially account for the initial formation of the large
      aggregation streams. Our observations indicate that Crp is important for both
      endocytosis and efflux and that defects in these functions lead to reduced growth
      and aberrant development.

PMID- 12074550
TI  - Sonic hedgehog signaling from the urethral epithelium controls external genital
      development.
AB  - External genital development begins with formation of paired genital swellings,
      which develop into the genital tubercle. Proximodistal outgrowth and axial
      patterning of the genital tubercle are coordinated to give rise to the penis or
      clitoris. The genital tubercle consists of lateral plate mesoderm, surface
      ectoderm, and endodermal urethral epithelium derived from the urogenital sinus.
      We have investigated the molecular control of external genital development in the
      mouse embryo. Previous work has shown that the genital tubercle has polarizing
      activity, but the precise location of this activity within the tubercle is
      unknown. We reasoned that if the tubercle itself is patterned by a specialized
      signaling region, then polarizing activity may be restricted to a subset of
      cells. Transplantation of urethral epithelium, but not genital mesenchyme, to
      chick limbs results in mirror-image duplication of the digits. Moreover, when
      grafted to chick limbs, the urethral plate orchestrates morphogenetic movements
      normally associated with external genital development. Signaling activity is
      therefore restricted to urethral plate cells. Before and during normal genital
      tubercle outgrowth, urethral plate epithelium expresses Sonic hedgehog (Shh). In
      mice with a targeted deletion of Shh, external genitalia are absent. Genital
      swellings are initiated, but outgrowth is not maintained. In the absence of Shh
      signaling, Fgf8, Bmp2, Bmp4, Fgf10, and Wnt5a are downregulated, and apoptosis is
      enhanced in the genitalia. These results identify the urethral epithelium as a
      signaling center of the genital tubercle, and demonstrate that Shh from the
      urethral epithelium is required for outgrowth, patterning, and cell survival in
      the developing external genitalia.

PMID- 12074549
TI  - Colony stimulating factor-1 is required to recruit macrophages into the mammary
      gland to facilitate mammary ductal outgrowth.
AB  - Mammary gland development initiates postnatally with the development of terminal
      end buds (TEBs) at the end of the rudimentary ducts. These grow out through the
      fat pad and bifurcate to lay down the rudimentary ductal tree. At the initiation
      of their development, TEBs recruit to their surrounding stroma a substantial
      population of macrophages. Using mice homozygous for a null mutation in the gene
      for the macrophage growth factor, colony stimulating factor-1 (CSF-1), that are
      severely depleted in macrophages, we demonstrated that CSF-1-regulated
      macrophages are required for normal branching morphogenesis in the mammary gland.
      However, these mice have a pleiotropic phenotype as a result of the generalized
      macrophage deficiency. To test that the effect of the mutation observed in the
      mammary gland was organ-autonomous, we developed a tetracycline-binary system
      whereby CSF-1 was specifically expressed in the mammary epithelium under the
      regulation of the MMTV-promoter. This restored mammary macrophage populations but
      not those in other tissues and corrected the branching morphogenesis defect.
      Inhibition of CSF-1 expression by tetracycline treatment for varying periods
      suggested that CSF-1-regulated macrophages are required throughout early mammary
      gland development. These data show that macrophages acting locally are required
      for branching morphogenesis of the mammary gland.

PMID- 12074551
TI  - Exploring myriapod segmentation: the expression patterns of even-skipped,
      engrailed, and wingless in a centipede.
AB  - Segment formation is critical to arthropod development, yet there is still
      relatively little known about this process in most arthropods. Here, we present
      the expression patterns of the genes even-skipped (eve), engrailed, and wingless
      in a centipede, Lithobius atkinsoni. Despite some differences when compared with
      the patterns in insects and crustaceans, the expression of these genes in the
      centipede suggests that their basic roles are conserved across the mandibulate
      arthropods. For example, unlike the seven pair-rule stripes of eve expression in
      the Drosophila embryonic germband, the centipede eve gene is expressed strongly
      in the posterior of the embryo, and in only a few stripes between newly formed
      segments. Nonetheless, this pattern likely reflects a conserved role for eve in
      the process of segment formation, within the different context of a short
      germband mode of embryonic development. In the centipede, the genes wingless and
      engrailed are expressed in stripes along the middle and posterior of each
      segment, respectively, similar to their expression in Drosophila. The adjacent
      expression of the engrailed and wingless stripes suggests that the regulatory
      relationship between the two genes may be conserved in the centipede, and thus
      this pathway may be a fundamental mechanism of segmental development in most
      arthropods.

PMID- 12074552
TI  - Chimeric analysis of retinoic acid receptor function during cardiac looping.
AB  - Retinoids (vitamin A and its derivatives) play essential roles during vertebrate
      development. Vitamin A deprivation leads to severe congenital malformations
      affecting many tissues, including diverse neural crest cell populations and the
      heart. The vitamin A signal is transduced by the retinoic acid receptors
      (RARalpha, RARbeta, and RARgamma). However, these receptors exhibit considerable
      functional redundancy, as judged by the mild phenotype of RAR single null mutants
      relative to the defects evoked by loss of multiple RARs. To circumvent this
      redundancy, the endogenous RARgamma2 allele was replaced with a ligand-binding
      RARgamma mutant (RARgammaE(305)) by gene targeting in mouse embryonic stem (ES)
      cells. Chimeric embryos derived from hemizygous RARgammaE(305) ES cells displayed
      several defects similar to those observed in certain RAR double null mutants,
      including hypoplasia or absence of the caudal pharyngeal arches and myocardial
      deficiencies. The latter defects were not due to abnormal cardiac specification
      as affected hearts still expressed chamber-specific markers in an appropriate
      manner. Chimeras also displayed cardiac looping anomalies, which were associated
      with a reduction of Pitx2. This work suggests a role for RAR signaling in late
      looping morphogenesis and illustrates the utility of using a dominant-negative
      gene substitution approach to circumvent the functional redundancy inherent to
      the RAR family.

PMID- 12074553
TI  - Genetic manipulation of single neurons in vivo reveals specific roles of flamingo
      in neuronal morphogenesis.
AB  - To study the roles of intracellular factors in neuronal morphogenesis, we used
      the mosaic analysis with a repressible cell marker (MARCM) technique to visualize
      identifiable single multiple dendritic (MD) neurons in living Drosophila larvae.
      We found that individual neurons in the peripheral nervous system (PNS) developed
      clear morphological polarity and diverse dendritic branching patterns in larval
      stages. Each MD neuron in the same dorsal cluster developed a unique dendritic
      field, suggesting that they have specific physiological functions. Single-neuron
      analysis revealed that Flamingo did not affect the general dendritic branching
      patterns in postmitotic neurons. Instead, Flamingo limited the extension of one
      or more dorsal dendrites without grossly affecting lateral branches. The
      dendritic overextension phenotype was partially conferred by the precocious
      initiation of dorsal dendrites in flamingo mutant embryos. In addition, Flamingo
      is required cell autonomously to promote axonal growth and to prevent premature
      axonal branching of PNS neurons. Our molecular analysis also indicated that the
      amino acid sequence near the first EGF motif is important for the proper
      localization and function of Flamingo. These results demonstrate that Flamingo
      plays a role in early neuronal differentiation and exerts specific effects on
      dendrites and axons.

PMID- 12074554
TI  - EphA4 constitutes a population-specific guidance cue for motor neurons.
AB  - Motor neurons in the ventral neural tube project axons specifically to their
      target muscles in the periphery. Although many of the transcription factors that
      specify motor neuron cell fates have been characterized, less is understood about
      the mechanisms that guide motor axons to their correct targets. We show that
      ectopic expression of EphA4 receptor tyrosine kinase alters the trajectories of a
      specific population of motor axons in the avian hindlimb. Most motor neurons in
      the medial portion of the lateral motor column (LMC) extend their axons
      aberrantly in the dorsal nerve trunk at the level of the crural plexus, in the
      presence of ectopic EphA4. This misrouting of motor axons is not accompanied by
      alterations in motor neuron identity, settling patterns in the neural tube, or
      the fasciculation of spinal nerves. However, ectopic EphA4 axons do make errors
      in pathway selection during sorting in the plexus at the base of the hindlimb.
      These results suggest that EphA4 in motor neurons acts as a population-specific
      guidance cue to control the dorsal trajectory of their axons in the hindlimb.

PMID- 12074555
TI  - Tissue-specific regulation of the LIM homeobox gene lin-11 during development of
      the Caenorhabditis elegans egg-laying system.
AB  - The egg-laying system of Caenorhabditis elegans hermaphrodites requires
      development of the vulva and its precise connection with the uterus. This process
      is regulated by LET-23-mediated epidermal growth factor signaling and LIN-12
      mediated lateral signaling pathways. Among the nuclear factors that act
      downstream of these pathways, the LIM homeobox gene lin-11 plays a major role.
      lin-11 mutant animals are egg-laying defective because of the abnormalities in
      vulval lineage and uterine seam-cell formation. However, the mechanisms providing
      specificity to lin-11 function are not understood. Here, we examine the
      regulation of lin-11 during development of the egg-laying system. Our results
      demonstrate that the tissue-specific expression of lin-11 is controlled by two
      distinct regulatory elements that function as independent modules and together
      specify a wild-type egg-laying system. A uterine pi lineage module depends on the
      LIN-12/Notch signaling, while a vulval module depends on the LIN-17-mediated Wnt
      signaling. These results provide a unique example of the tissue-specific
      regulation of a LIM homeobox gene by two evolutionarily conserved signaling
      pathways. Finally, we provide evidence that the regulation of lin-11 by LIN
      12/Notch signaling is directly mediated by the Su(H)/CBF1 family member LAG-1.

PMID- 12074556
TI  - A role for the RNA-binding protein, hermes, in the regulation of heart
      development.
AB  - RNA-binding proteins are known to play an important role in a number of aspects
      of development, although in most cases the precise mechanism of action remains
      unknown. We have previously described the isolation of an RNA-binding protein,
      hermes, that is expressed at very high levels in the differentiating myocardium.
      Here, we report experiments aimed at elucidating the functional role of hermes in
      development. Utilizing the Xenopus oocyte, we show that hermes is localized
      primarily to the cytoplasm, can associate in a multiprotein complex, and is able
      to bind to mature RNA transcripts in vivo. Overexpression of hermes in the
      developing embryo dramatically and specifically inhibits heart development. In
      particular, transcripts encoding the myocardial differentiation markers, cardiac
      troponin I and cardiac alpha-actin, are absent, and overall morphological
      development of the heart is eliminated. Examination of markers of precardiac
      tissue showed that expression of GATA-4 is normal, while the levels of Nkx2-5
      mRNA are strongly reduced. Overall, these studies suggest that hermes plays a
      role in the regulation of mature transcripts required for myocardial
      differentiation. To our knowledge, this is the first evidence for an RNA-binding
      protein playing a direct role in regulation of vertebrate heart development.

PMID- 12074557
TI  - Downstream targets of let-60 Ras in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as
      differentiation of vulval epithelial cells, function of chemosensory neurons, and
      meiotic progression in the germ line. Although much is known about the let-60 Ras
      signaling pathway, relatively little is understood about the target genes induced
      by let-60 Ras signaling that carry out terminal effector functions leading to
      morphological change. We have used DNA microarrays to identify 708 genes that
      change expression in response to activated let-60 Ras.

PMID- 12074558
TI  - Distinct patterns of downstream target activation are specified by the helix-loop
      helix domain of proneural basic helix-loop-helix transcription factors.
AB  - Both gain- and loss-of-function analyses indicate that proneural basic/helix-loop
      helix (bHLH) proteins direct not only general aspects of neuronal differentiation
      but also specific aspects of neuronal identity within neural progenitors. In
      order to better understand the function of this family of transcription factors,
      we have used hormone-inducible fusion constructs to assay temporal patterns of
      downstream target regulation in response to proneural bHLH overexpression. In
      these studies, we have compared two distantly related Xenopus proneural bHLH
      genes, Xash1 and XNgnr1. Our findings indicate that both Xash1 and XNgnr1 induce
      expression of the general neuronal differentiation marker, N-tubulin, with a
      similar time course in animal cap progenitor populations. In contrast, these
      genes each induce distinct patterns of early downstream target expression. Both
      genes induce expression of the HLH-containing gene, Xcoe2, at early time points,
      but only XNgnr1 induces early expression of the bHLH genes, Xath3 and XNeuroD.
      Structure:function analyses indicate that the distinct pattern of XNgnr1-induced
      downstream target activation is linked to the XNgnr1 HLH domain, demonstrating a
      novel role for this domain in mediating the differential function of individual
      members of the proneural bHLH gene family.

PMID- 12074559
TI  - Nonequivalence of maternal centrosomes/centrioles in starfish oocytes: selective
      casting-off of reproductive centrioles into polar bodies.
AB  - It is believed that in most animals only the paternal centrosome provides the
      division poles for mitosis in zygotes. This paternal inheritance of the
      centrosomes depends on the selective loss of the maternal centrosome. In order to
      understand the mechanism of centrosome inheritance, the behavior of all maternal
      centrosomes/centrioles was investigated throughout the meiotic and mitotic cycles
      by using starfish eggs that had polar body (PB) formation suppressed. In starfish
      oocytes, the centrioles do not duplicate during meiosis II. Hence, each
      centrosome of the meiosis II spindle has only one centriole, whereas in meiosis
      I, each has a pair of centrioles. When two pairs of meiosis I centrioles were
      retained in the cytoplasm of oocytes by complete suppression of PB extrusion,
      they separated into four single centrioles in meiosis II. However, after
      completion of the meiotic process, only two of the four single centrioles were
      found in addition to the pronucleus. When the two single centrioles of a meiosis
      II spindle were retained in the oocyte cytoplasm by suppressing the extrusion of
      the second PB, only one centriole was found with the pronucleus after the
      completion of the meiotic process. When these PB-suppressed eggs were
      artificially activated to drive the mitotic cycles, all the surviving single
      centrioles duplicated repeatedly to form pairs of centrioles, which could
      organize mitotic spindles. These results indicate that the maternal centrioles
      are not equivalent in their intrinsic stability and reproductive capacity. The
      centrosomes with the reproductive centrioles are selectively cast off into the
      PBs, resulting in the mature egg inheriting a nonreproductive centriole, which
      would degrade shortly after the completion of meiosis.

PMID- 12074560
TI  - The planar cell polarity gene strabismus regulates convergence and extension and
      neural fold closure in Xenopus.
AB  - We cloned Xenopus Strabismus (Xstbm), a homologue of the Drosophila planar cell
      or tissue polarity gene. Xstbm encodes four transmembrane domains in its N
      terminal half and a PDZ-binding motif in its C-terminal region, a structure
      similar to Drosophila and mouse homologues. Xstbm is expressed strongly in the
      deep cells of the anterior neural plate and at lower levels in the posterior
      notochordal and neural regions during convergent extension. Overexpression of
      Xstbm inhibits convergent extension of mesodermal and neural tissues, as well as
      neural tube closure, without direct effects on tissue differentiation. Expression
      of Xstbm(DeltaPDZ-B), which lacks the PDZ-binding region of Xstbm, inhibits
      convergent extension when expressed alone but rescues the effect of
      overexpressing Xstbm, suggesting that Xstbm(DeltaPDZ-B) acts as a dominant
      negative and that both increase and decrease of Xstbm function from an optimum
      retards convergence and extension. Recordings show that cells expressing Xstbm or
      Xstbm(DeltaPDZ-B) fail to acquire the polarized protrusive activity underlying
      normal cell intercalation during convergent extension of both mesodermal and
      neural and that this effect is population size-dependent. These results further
      characterize the role of Xstbm in regulating the cell polarity driving
      convergence and extension in Xenopus.

PMID- 12074561
TI  - Arylsulfatase a is present on the pig sperm surface and is involved in sperm-zona
      pellucida binding.
AB  - We have previously described the affinity of a pig sperm surface protein, P68, to
      mammalian zonae pellucidae (ZP). In this report, we identified P68 as
      arylsulfatase A (AS-A) based on the presence of P68 tryptic peptide sequences in
      the pig testis AS-A cDNA sequence. Our objective was to demonstrate the presence
      of AS-A on the sperm surface and to elucidate its role in ZP binding. Immunogold
      electron microscopy revealed the presence of AS-A on the sperm surface.
      Furthermore, live pig sperm and the extract of peripheral sperm plasma membrane
      proteins exhibited AS-A's desulfation activity. Significantly, the role of pig
      sperm surface AS-A in ZP binding was demonstrated by dose-dependent decreases of
      sperm-ZP binding upon sperm pretreatment with anti-AS-A IgG/Fab, and by the
      binding of Alexa-430-conjugated sperm surface AS-A to homologous ZP. ZP
      pretreatment with anti-pig-ZP3 antibody abolished AS-A binding, suggesting that
      ZP3, recognized as the pig sperm receptor, was AS-A's binding ligand. This was
      further confirmed by the ability of exogenous ZP3 to competitively inhibit AS-A
      ZP binding. Similarly, purified ZP3alpha, a major sperm receptor component of
      ZP3, exhibited great inhibitory effect on AS-A-ZP binding. All of these results
      designated a new function of AS-A in gamete interaction.

PMID- 12074562
TI  - Homeobox gene hoxa3 is essential for the formation of the carotid body in the
      mouse embryos.
AB  - Homeobox gene Hoxa3 is strongly expressed in the third pharyngeal arch and pouch.
      We found that Hoxa3 homozygous null mutant mice had the lack of the carotid body.
      In all late-term mutant embryos examined (n = 10), no carotid body was present.
      The carotid body rudiment is formed in the wall of the third branchial artery,
      which develops into the common carotid artery and the first part of the internal
      carotid artery. The symmetrical patterns of the third, fourth, and sixth arch
      arteries were observed in wild-type littermates at embryonic day (E) 10.5-12.5.
      In Hoxa3 homozygous mutant embryos, however, the third arch artery began to
      degenerate at E10.5 and almost disappeared at E11.5. Furthermore, the bifurcation
      of the common carotid artery at the normal position, i.e., at the upper end of
      the larynx, was never detected in the mutant embryos at E16.5-E18.5. The common
      carotid artery of the homozygous mutants was separated into the internal and
      external carotid arteries immediately after its origin. Thus, the present study
      evidenced that the absence of the carotid body in Hoxa3 homozygous mutants is due
      to the defect of development of the third arch artery, resulting in malformation
      of the carotid artery system. During fetal development, the carotid body of mice
      is in close association with the superior cervical ganglion of the sympathetic
      trunk. The superior cervical ganglion rather showed hypertrophic features in
      Hoxa3 homozygous mutants lacking the carotid body.

PMID- 12074563
TI  - Inhibition of MEK or cdc2 kinase parthenogenetically activates mouse eggs and
      yields the same phenotypes as Mos(-/-) parthenogenotes.
AB  - Mammalian eggs are arrested in metaphase II of meiosis until fertilization.
      Arrest is maintained by cytostatic factor (CSF) activity, which is dependent on
      the MOS-MEK-MAPK pathway. Inhibition of MEK1/2 with a specific inhibitor, U0126,
      parthenogenetically activated mouse eggs, producing phenotypes similar to Mos(-/
      ) parthenogenotes (premature, unequal cleavages and large polar bodies). U0126
      inactivated MAPK in eggs within 1 h, in contrast to the 5 h required after
      fertilization, while the time course of MPF inactivation was similar in U0126
      activated and fertilized eggs. We also found that inactivation of MPF by the cdc2
      kinase inhibitor roscovitine induced parthenogenetic activation. Inactivation of
      MPF by roscovitine resulted in the subsequent inactivation of MAPK with a time
      course similar to that following fertilization. Notably, roscovitine also
      produced some Mos(-/-)-like phenotypes, indistinguishable from U0126
      parthenogenotes. Simultaneous inhibition of both MPF and MAPK in eggs treated
      with roscovitine and U0126 produced a very high proportion of eggs with the more
      severe phenotype. These findings confirm that MEK is a required component of CSF
      in mammalian eggs and imply that the sequential inactivation of MPF followed by
      MAPK inactivation is required for normal spindle function and polar body
      emission.

PMID- 12074564
TI  - Neuritogenesis: polarization of constitutive exocytosis by effectors of Rho
      family GTPases?
AB  - The sprouting of neurites from a neuron represents a highly specialized form of
      cellular morphogenesis that must involve coordinated changes in two major
      cellular processes at two membrane locations: reorganization of the cytoskeleton
      and redirection of membrane traffic from the trans-Golgi network to the plasma
      membrane of the growth tip. How exactly are these two processes linked and how is
      spatial and temporal coordination achieved at the first instance of neurite
      sprouting? Recent advances may have already revealed some, if not most of the
      pieces in the puzzle. We discuss below, with some extrapolations, of what has
      recently come to light, and what more is needed to construct a coherent picture.

PMID- 12074565
TI  - Membrane association of estrogen receptor alpha mediates estrogen effect on MAPK
      activation.
AB  - Estrogen rapidly activates MAPK in many cell types but the mechanisms have not
      been fully understood. We previously demonstrated that 17-beta-estradiol
      (estradiol) rapidly induced membrane translocation of estrogen receptor alpha
      (ERalpha) and activated MAPK in MCF-7 breast cancer cells. This study further
      determines the cause and effect relationship between the presence of membrane
      ERalpha and MAPK activation. ERalpha with a membrane localization signal (HE241G
      mem) was expressed and compared with the ones in nucleus (HEGO) or cytosol
      (HE241G) localization. Confocal microscopy showed that HE241G-mem was expressed
      in the cell membrane as well as in the cytosol in COS-1 cells. HE241G localized
      in the cytosol and HEGO in the nucleus. Functional studies showed that only
      membrane ERalpha, not cytosol and nuclear ones, responded to estradiol by
      inducing MAPK phosphorylation. HE241G-mem neither increased basal nor estradiol
      induced ERE promoter activation, indicating no transcriptional action involved.
      Our data support the view that membrane-associated ERalpha is critical in
      estrogen-initiated MAPK activation.

PMID- 12074566
TI  - Necrosis has orderly DNA fragmentations.
AB  - Necrosis from freezing manifested an orderly pattern of DNA fragmentations,
      including the apoptosis signature of 200 bp ladder, in three different cell
      populations, despite pancaspase suppression by zVAD-fmk. Immediately on thawing,
      all three populations had 100% dead cell indices and 2.2, 1.6, and 1.1 megabase
      fragmentations, which marked the point of death. Kilobase and 200 bp DNA ladder
      fragmentations manifested later together with overt necrotic morphologies. CpG
      oligodeoxynucleotides (ODNs) complementary to highly conserved GCn(x)GC motifs
      inhibited the megabase fragmentations and retarded their electrophoretic mobility
      (gel shift), indicating ODN-DNA binding, which is known to confer site-specific
      resistance to cleavage. Cleavage specificity was confirmed using EDTA-CpG ODN
      conjugates to direct free-radical-producing transitional element, vanadyl(4), to
      the binding sites to reproduce the megabase fragmentations in normal cells.
      Specific orderly fragmentations in necrosis suggested a necrosis-apoptosis
      convergence after death has been committed.

PMID- 12074568
TI  - The P1' specificity of tobacco etch virus protease.
AB  - Affinity tags have become indispensable tools for protein expression and
      purification. Yet, because they have the potential to interfere with structural
      and functional studies, it is usually desirable to remove them from the target
      protein. The stringent sequence specificity of the tobacco etch virus (TEV)
      protease has made it a useful reagent for this purpose. However, a potential
      limitation of TEV protease is that it is believed to require a Gly or Ser residue
      in the P1' position of its substrates to process them with reasonable efficiency.
      Consequently, after an N-terminal affinity tag is removed by TEV protease, the
      target protein will usually retain a non-native Ser or Gly residue on its N
      terminus, and in some cases this may affect its biological activity. To
      investigate the stringency of the requirement for Gly or Ser in the P1' position
      of a TEV protease recognition site, we constructed 20 variants of a fusion
      protein substrate with an otherwise optimal recognition site, each containing a
      different amino acid in the P1' position. The efficiency with which these fusion
      proteins were processed by TEV protease was compared both in vivo and in vitro.
      Additionally, the kinetic parameters K(M) and k(cat) were determined for a
      representative set of peptide substrates with amino acid substitutions in the P1'
      position. The results indicate that many side-chains can be accommodated in the
      P1' position of a TEV protease recognition site with little impact on the
      efficiency of processing.

PMID- 12074567
TI  - Betaig-h3 supports keratinocyte adhesion, migration, and proliferation through
      alpha3beta1 integrin.
AB  - betaig-h3 is an extracellular matrix protein and its expression is highly induced
      by TGF-beta and it has also been suggested to play important roles in skin wound
      healing. In this paper, we demonstrate that betaig-h3 is present in the papillary
      layer of dermis and synthesized in the basal keratinocytes in vivo and its
      expression is induced by TGF-beta in normal human keratinocytes (NHEK) and HaCaT
      cells. betaig-h3 mediates not only adhesion and spreading of keratinocytes but
      also supports migration and proliferation. These activities are mediated through
      interacting with alpha3beta1 integrin. Previously identified two alpha3beta1
      integrin-interacting motifs of betaig-h3, EPDIM, and NKDIL, are responsible for
      these activities. The results suggest that betaig-h3 may regulate keratinocyte
      functions in normal skin and potentially during wound-healing process.

PMID- 12074569
TI  - Involvement of CCAAT/enhancer-binding protein alpha in haptoglobin gene
      expression by all-trans-retinoic acid.
AB  - Several acute-phase plasma proteins, including haptoglobin (Hp), are induced in
      the liver in response to inflammation. Recently, we found that Hp gene expression
      is up-regulated by all-trans-retinoic acid (ATRA) in the extrahepatic monocytic
      cell line, THP-1. To investigate the molecular mechanism underlying ATRA-induced
      Hp gene expression, we analyzed the induction of transcription factor
      CCAAT/enhancer-binding protein (C/EBP) isoforms in ATRA-stimulated THP-1 cells
      and their binding to the Hp promoter. Western blot analysis showed that treatment
      with ATRA increased C/EBPalpha and beta expression, but decreased that of
      C/EBPdelta. Electrophoretic mobility shift and supershift assays demonstrated
      that only C/EBPalpha of the C/EBP isoforms bound to the C/EBP DNA-binding sites
      in the Hp promoter. Furthermore, when ATRA-dependent Hp induction was inhibited
      by sodium butyrate or auranofin, induction of C/EBPalpha, but not C/EBPbeta, was
      also diminished. These results suggest that C/EBPalpha is involved in the
      activation of Hp gene expression by ATRA in human monocytic cells.

PMID- 12074570
TI  - Amino acids control ammonia pulses in yeast colonies.
AB  - Individual yeast colonies produce pulses of volatile ammonia separated by phases
      of medium acidification. Colonies of Saccharomyces cerevisiae mutant defective in
      the general amino acid permease, Gap1p, exhibit decreased ammonia production.
      Mutations in the S. cerevisiae amino acid sensor SPS completely abolish the
      colony ammonia pulses. In contrast, the ammonia pulse production is independent
      of external concentrations of ammonium and of its uptake by the ammonium
      permeases Mep1p, Mep2p, and Mep3p. It is concluded that in S. cerevisiae
      colonies, the extracellular amino acids, but not the extracellular ammonium,
      serve as a source for volatile ammonia production. These phenomena are not
      restricted to S. cerevisiae, since we observe that extracellular levels of 8 out
      of the 20 tested amino acids are necessary for ammonia pulses produced by Candida
      mogii colonies.

PMID- 12074571
TI  - Dimerization is required for phosphorylation and DNA binding of TonEBP/NFAT5.
AB  - TonEBP (NFAT5) is a newly identified member of the Rel family of transcriptional
      activators that include NF-kappaB and NFAT1 to NFAT4. Activated in response to
      hypertonicity, TonEBP stimulates transcription of transporters of organic
      osmolytes, certain cytokines, and a molecular chaperone. We provide biochemical
      data demonstrating that full-length TonEBP dimerizes via the C-terminus of the
      Rel-homology domain (CRHD). The two polyglutamine motifs were not involved. The
      dimerization was not affected by nucleocytoplasmic shifts in TonEBP in response
      to changes in ambient tonicity. Preventing the dimer formation by deleting the
      CRHD did not affect the nucleocytoplasmic shifts. On the other hand, deletion of
      the CRHD prevented DNA binding and eliminated the dominant negative activity of a
      C-terminal truncated TonEBP. Furthermore, phosphorylation was dramatically
      reduced especially in hypertonic conditions by deletion of the CRHD. We conclude
      that dimerization is required for proper phosphorylation of TonEBP as well as DNA
      binding.

PMID- 12074572
TI  - Cell adhesion protects c-Raf-1 against ubiquitin-dependent degradation by the
      proteasome.
AB  - MAP kinase activation by growth factors depends on cell adhesion to the
      extracellular matrix. Disrupting the cell adhesion process in NIH 3T3 fibroblasts
      induced an almost complete inhibition of MAP kinase, which was impaired by
      proteasome inhibitors. In the absence of cell anchorage, c-Raf-1 expression was
      dramatically decreased after 24 h. This down-regulation was suppressed by
      proteasome inhibitors, suggesting that a proteasome-dependent degradation of Raf
      occurred in the absence of cell adhesion. Proteasome inhibitors did not affect
      Raf-1 levels in adherent cells, indicating that this degradation only occurred in
      the absence of cell adhesion. Finally, ectopic coexpression of Raf-1 and
      ubiquitin in HEK-293 and NIH 3T3 cells generated ubiquitylated forms of Raf-1,
      both in adherent and suspended cells, suggesting a possible ubiquitin-dependent
      degradation of the protein.

PMID- 12074574
TI  - A non-IGF binding mutant of IGFBP-3 modulates cell function in breast epithelial
      cells.
AB  - We demonstrated previously that IGFBP-3 alone had no effect on cell death, but
      dramatically modulated apoptosis in Hs578T IGF non-responsive cells. We
      investigated whether a non-IGF binding mutant of IGFBP-3 retained its intrinsic
      actions in this cell line, prior to investigating its actions in IGF-responsive
      cells (MCF-7 and MCF-10A). In the Hs578T cells, the ceramide analogue, C2-induced
      apoptosis, non-glycosylated, glycosylated or mutant IGFBP-3 alone had no effect
      but on co-incubation with C2, all forms of IGFBP-3 markedly accentuated triggered
      apoptosis. In MCF-7 cells, IGFBP-3 was unable to modulate C2-induced death. In
      the MCF-10A cells, IGFBP-3 acted as a potent survival factor. IGFBP-3 also
      affected cell growth in the MCF-10A cells (inhibiting at low doses but increasing
      growth at higher concentrations). These actions of IGFBP-3 in the MCF-10A cells
      were independent of IGF-1. IGFBP-3 has differential IGF-independent effects on
      cell death and growth in normal breast and breast cancer cells.

PMID- 12074573
TI  - Inhibition of Rho-kinase induces alphaB-crystallin expression in lens epithelial
      cells.
AB  - The small heat shock protein, alphaB-crystallin, has been shown to interact with
      actin and intermediate filament proteins. However, little is known regarding the
      cellular mechanisms regulating such interactions. In this study, we explored the
      role of the Rho/Rho-kinase pathway in alphaB-crystallin distribution and
      expression in porcine lens epithelial cells. alphaB-crystallin was distributed
      uniformly throughout the cytoplasm and did not exhibit any unique redistribution
      in response to actin depolymerization induced by Rho/Rho-kinase inhibitors (C3
      exoenzyme or Y-27632) or by overexpression of the dominant negative mutant of Rho
      kinase (DNRK) in porcine lens epithelial cells. Interestingly, alphaB-crystallin
      levels markedly increased in lens epithelial cells treated with the inhibitors of
      Rho/Rho-kinase proteins (lovastatin, Y-27632 or DNRK) while a protein kinase C
      inhibitor (GF109203x) was found to have no effect. Further, Y-27632 showed a dose
      (2-50 microM) response effect on alphaB-crystallin induction. Nocodazole, a
      microtubule-depolymerizing agent, elicited an increase in alphaB-crystallin
      levels but latrunculin, an actin depolymerizing agent, did not show any
      significant effect. Pretreatment with cycloheximide or genistein blocked the Rho
      kinase inhibitor-induced increase in alphaB-crystallin protein levels. Rho-kinase
      inhibitor-induced increases in alphaB-crystallin levels were found to be
      associated with activation of P38 mitogen-activated protein kinase (MAPK). These
      results suggest that Rho/Rho-kinase negatively regulates alphaB-crystallin
      expression, and this response appears to be dependent on tyrosine-protein kinase
      and P38 MAPK function. Finally, alphaB-crystallin induction appears to be better
      correlated with the direct inhibition of Rho/Rho-kinase than with actin
      depolymerization per se.

PMID- 12074575
TI  - Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast
      cancer cells.
AB  - We have demonstrated previously that IGFBP-5 alone had no effect on cell death
      but modulated ceramide-induced apoptosis in Hs578T IGF non-responsive cells. To
      investigate if IGFBP-5 maintains its intrinsic ability to modulate apoptosis in
      IGF-responsive cells, we used a non-IGF binding mutant of IGFBP-5. In Hs578T
      cells, non-glycosylated, glycosylated or mutant IGFBP-5 alone each had no effect
      on cell death, whereas all forms inhibited ceramide-induced apoptosis. In IGF
      responsive MCF-7 cells, each wild type form reduced ceramide-induced cell death
      but mutant IGFBP-5 was without effect. In the presence of mutant IGFBP-5,
      however, IGF-I no longer conferred survival and in the presence of wild type
      IGFBP-5, long R3 IGF-I was also unable to confer survival. In summary, all forms
      of IGFBP-5 modulated ceramide-induced apoptosis in Hs578T cells. In MCF-7 cells,
      IGF-I-induced survival could be facilitated by IGFBP-5, but also blocked by IGFBP
      5 if association with IGFBP-5 was prevented.

PMID- 12074576
TI  - Thrombin-stimulated Pyk2 phosphorylation in human endothelium is dependent on
      intracellular calcium and independent of protein kinase C and Src kinases.
AB  - G-protein-coupled receptor agonists (GPCAs) cause functional responses in
      endothelial cells including secretion, proliferation, and altering monolayer
      permeability. These events are mediated in part by activation of the p42/44
      mitogen-activated protein kinase (MAPK) cascade. The cytosolic tyrosine kinase
      Pyk2 is postulated to link GPCA-induced changes in intracellular calcium to
      activation of the MAP kinase cascade. We have investigated the regulation of Pyk2
      in human umbilical vein endothelial cells in response to GPCAs and show that (1)
      thrombin, a PAR-1 peptide, and histamine cause rapid concentration- and time
      dependent phosphorylation on tyrosines 402 (Src kinase binding site), 881 (Grb2
      binding site), and 580 (an autophosphorylation site), (2) thrombin-stimulated
      phosphorylation is dependent on intracellular calcium and independent of PKC and
      PI-3 kinase, and (3) inhibition of Src kinases has no significant effect on
      thrombin-stimulated phosphorylation, implying that tyrosine phosphorylation of
      Pyk2 is independent of Src binding.

PMID- 12074577
TI  - Isolation of novel rice (Oryza sativa L.) multiple stress responsive MAP kinase
      gene, OsMSRMK2, whose mRNA accumulates rapidly in response to environmental cues.
AB  - In search for components of MAPK (mitogen-activated protein kinase) cascades in
      rice (Oryza sativa L. cv. Nipponbare), we identified a single copy gene called
      OsMSRMK2 from jasmonic acid (JA) treated rice seedling leaf cDNA library. This
      gene has a conserved protein kinase domain, including a MAPK family signature,
      and encodes a 369 amino acid polypeptide with a predicted molecular mass of
      42995.43 and a pI of 5.48. OsMSRMK2 did not show constitutive expression in
      leaves and was induced within 15 min in response to wounding by cut. Using in
      vitro system, we show that the expression of OsMSRMK2 mRNA was potently enhanced
      within 15 min by signalling molecules, protein phosphatase inhibitors,
      ultraviolet irradiation, fungal elicitor, heavy metals, high salt and sucrose,
      and drought. OsMSRMK2 expression was further modulated by co-application of JA,
      salicylic acid, and ethylene and required de novo synthesized protein factor(s)
      in its transient regulation. Moreover, high (37 degrees C) and low temperatures
      (12 degrees C) and environmental pollutants-ozone and sulfur dioxide
      differentially regulate the OsMSRMK2 mRNA accumulation in leaves of intact
      plants. Present results demonstrating dramatic transcriptional and transient
      regulation of the OsMSRMK2 expression by diverse biotic/abiotic stresses, a first
      report for any rice (or plant) MAPK to date, suggest a role for OsMSRMK2 in rice
      defense/stress response pathways.

PMID- 12074578
TI  - PDGF-BB enhances expression of, and reduces adhesion to, laminin-5 in vascular
      smooth muscle cells.
AB  - The laminin family of extracellular matrix (ECM) proteins plays crucial roles in
      regulating cellular growth, migration, and differentiation. We report here that
      laminin-5 is expressed in the tunica media of the rat aorta and pulmonary
      arteries. Using indirect immunofluorescence microscopy, Western blots, and RT-PCR
      analysis, we found that primary cultures of rat arterial smooth muscle cells
      express laminin-5 and deposit it into their insoluble ECM. These cells also
      attach strongly to laminin-5 via beta1 integrin receptors in 30 min adhesion
      assays. Laminin-5 expression in these cells is upregulated by growth factors in
      vitro and platelet-derived growth factor (PDGF-BB) stimulation reduces adhesion
      to laminin-5. As laminin-5 promotes enhanced migration of other cell types, the
      production of and adhesion to laminin-5 by vascular smooth muscle cells may play
      a role in the pathological growth and migration of these cells associated with
      restenosis following vascular injury.

PMID- 12074579
TI  - Metalloprotease inhibitor blocks angiotensin II-induced migration through
      inhibition of epidermal growth factor receptor transactivation.
AB  - In vascular smooth muscle cells (VSMCs), angiotensin II (AngII) induces
      transactivation of the EGF receptor (EGFR) which involves a metalloprotease that
      stimulates processing of heparin-binding EGF from its precursor. However, the
      identity and pharmacological sensitivity of the metalloprotease remain unclear.
      Here, we screened the effects of several metalloprotease inhibitors on AngII
      induced EGFR transactivation in VSMCs. We found that an N-phenylsulfonyl
      hydroxamic acid derivative [2R-[(4-biphenylsulfonyl)amino]-N-hydroxy-3
      phenylpropinamide] (BiPS), previously known as matrix metalloprotease (MMP)-2/9
      inhibitor, markedly inhibited AngII-induced EGFR transactivation, whereas the MMP
      2 or -9 inhibition by other MMP inhibitors failed to block the transactivation.
      BiPS markedly inhibited AngII-induced ERK activation and protein synthesis
      without affecting AngII-induced intracellular Ca2+ elevation. VSMC migration
      induced by AngII was also inhibited not only by an EGFR inhibitor but also by
      BiPS. Thus, BiPS is a specific candidate to block AngII-induced EGFR
      transactivation and subsequent growth and migration of VSMCs, suggesting its
      potency to prevent vascular remodeling.

PMID- 12074580
TI  - Lack of nitric oxide synthase depresses ion transporting enzyme function in
      cardiac muscle.
AB  - Nitric oxide (NO*) is produced endogenously from NOS isoforms bound to
      sarcolemmal (SL) and sarcoplasmic reticulum (SR) membranes. To investigate
      whether locally generated NO* directly affects the activity of enzymes mediating
      ion active transport, we studied whether knockout of selected NOS isoforms would
      affect the functions of cardiac SL (Na+ + K+)-ATPase and SR Ca2+-ATPase. Cardiac
      SL and SR vesicles containing either SL (Na+ + K+)-ATPase or SR Ca2+-ATPase were
      isolated from mice lacking either nNOS or eNOS, or both, and tested for enzyme
      activities. Western blot analysis revealed that absence of single or double NOS
      isoforms did not interrupt the protein expression of SL (Na+ + K+)-ATPase and SR
      Ca2+-ATPase in cardiac muscle cells. However, lack of NOS isoforms in cardiac
      muscle significantly altered both (Na+ + K+)-ATPase activity and SR Ca2+-ATPase
      function. Our experimental results suggest that disrupted endogenous NO*
      production may change local redox conditions and lead to an unbalanced free
      radical homeostasis in cardiac muscle cells which, in turn, may affect key enzyme
      activities and membrane ion active transport systems in the heart.

PMID- 12074581
TI  - Nurr1 affects pRL-TK but not phRG-B internal control plasmid in genetic reporter
      system.
AB  - In transcription assays, Renilla luciferase-expressing plasmids (more
      specifically pRL-TK) are commonly used as an internal control of transfection
      efficiency. Normalization of the experimental reporter gene transcription to the
      internal control reporter gene transcription minimizes variability of obtained
      results caused by differences in transfection efficiency between different
      samples of transfected cells. It is obvious that co-transfection with other
      plasmids or applied treatments should not affect the activity of the control
      reporter. Here we report that expression of the control Renilla luciferase
      encoded by pRL-TK plasmid was enhanced by co-transfection with vectors expressing
      orphan nuclear receptors Nur77 family (Nur77, Nurr1, Nor-1), leading to
      misinterpretation of the assay results. Further, we show that for Nurr1, phRG-B
      (a promoterless reporter plasmid containing synthetic Renilla luciferase gene) is
      a better control reporter vector than HSV-TK containing vectors. Finally, we
      noted the lack of effect of Nurr1 protein on the Fas Ligand promoter-driven
      transcription.

PMID- 12074582
TI  - Solution structure of betacellulin, a new member of EGF-family ligands.
AB  - The solution structure of the EGF-like domain of betacellulin (BTCe), a newly
      discovered member of the epidermal growth factor (EGF) family, has been
      determined using two-dimensional nuclear magnetic resonance spectroscopy. This is
      the first report to identify the solution structure of the EGF-family ligand
      monomers that interact with both ErbB-1 and ErbB-4. The solution structure of
      BTCe was calculated using 538 NMR-derived restraints. The overall structure of
      BTCe was stabilized by three disulfide bonds, a hydrophobic core, and 23 hydrogen
      bonds. It appears that BTCe is comprised of five beta-strands and one short 3(10)
      helical turn. The secondary structural elements of BTCe are basically similar to
      those of the other EGF-family proteins, except that several significant
      variations of the structural properties were found. It is suggested that the
      structural variations between BTCe and the other EGF-family ligands may affect
      the specific receptor-recognition properties of EGF-family ligands.

PMID- 12074583
TI  - The presence of D-beta-aspartic acid-containing peptides in elastic fibers of sun
      damaged skin: a potent marker for ultraviolet-induced skin aging.
AB  - Biologically uncommon d-aspartyl residues have been reported in proteins of
      various elderly tissues. We prepared a polyclonal antibody against d-beta-Asp
      containing peptide and examined its immunoreactivity in the skin. The antibody
      recognized integrated or disintegrated elastic fibers in the sun-exposed skin but
      not in the sun-protected skin of the elderly donors. Western blot analysis of the
      proteins isolated from sun-damaged skin demonstrated that the 50 kDa protein was
      immunoreactive with both antibodies for d-beta-Asp-containing peptide and
      elastin. Ultraviolet (UV) irradiation on normal skin caused the appearance of d
      beta-Asp-containing peptide-immunoreactive fibers in the dermis. These results
      suggest that UV irradiation is closely related to the formation of d-beta-Asp in
      the elastic fibers of skin. We propose that the antibody could be a useful
      indicator for sun damage of the skin.

PMID- 12074585
TI  - The truncated hemoglobin from Mycobacterium leprae.
AB  - Truncated hemoglobins (trHb's) form a family of low molecular weight O2 binding
      hemoproteins distributed in eubacteria, protozoa, and plants. TrHb's branch in a
      distinct clade within the hemoglobin (Hb) superfamily. A unique globin gene has
      recently been identified from the complete genome sequence of Mycobacterium
      leprae that is predicted to encode a trHb (M. leprae trHbO). Sequence comparison
      and modelling considerations indicate that monomeric M. leprae trHbO has
      structural features typical of trHb's, such as 20-40 fewer residues than
      conventional globin chains, Gly-based sequence consensus motifs, likely
      assembling into a 2-on-2 alpha-helical sandwich fold, and hydrophobic residues
      recognized to build up the protein matrix ligand diffusion tunnel. The ferrous
      heme iron atom of deoxygenated M. leprae trHbO appears to be hexacoordinated,
      like in Arabidopsis thaliana trHbO-3 (A. thaliana trHbO-3). Accordingly, the
      value of the second-order rate constant for M. leprae trHbO carbonylation (7.3 x
      10(3) M(-1) s(-1)) is similar to that observed for A. thaliana trHbO-3 (1.4 x
      10(4) M(-1) s(-1)) and turns out to be lower than that reported for carbon
      monoxide binding to pentacoordinated Mycobacterium tuberculosis trHbN (6.7 x
      10(6) M(-1) s(-1)). The lower reactivity of M. leprae trHbO as compared to M.
      tuberculosis trHbN might be related to the higher susceptibility of the leprosy
      bacillus to toxic nitrogen and oxygen species produced by phagocytic cells.

PMID- 12074584
TI  - Downregulation of beta2-microglobulin in human cord blood somatic stem cells
      after transplantation into livers of SCID-mice: an escape mechanism of stem
      cells?
AB  - Adherently growing, non-hematopoietic somatic stem cells isolated from human cord
      blood were stained with the fluorescent dye PKH26 and transplanted into livers of
      SCID-mice to examine a possible cell fate transition. Already 7 days after
      transplantation stem cells were well integrated into the liver tissue. Human
      albumin that was not expressed by the stem cells before transplantation was
      detectable in the host's livers after injection of cord blood stem cells. Human
      alpha1-antitrypsin was detectable in stem cells already before transplantation
      and remained positive in the mouse liver. The most interesting observation in
      this study was the downregulation of human beta2-microglobulin (beta2M) in the
      stem cells after transplantation: beta2M is expressed constitutively in our cord
      blood stem cells. However, beta2M was no longer detectable by RT-PCR in all
      tissues where human albumin and alpha1-antitrypsin were expressed after stem cell
      transplantation. beta2M is known to participate as an integral part of the major
      histocompatibility complex. Absence of beta2M makes the residual heavy chain
      inactive as an antigen. Thus, downregulation of beta2M may represent an escape
      mechanism from killer-T cells and may be a molecular mechanism explaining the
      recently described "immunological blindness" [37] of stem cells. In contrast to
      the results obtained after direct injection of stem cells as a suspension, no
      consistent downregulation of beta2M was observed after transplantation of stem
      cells encapsulated in alginate beads to generate a compartment where stem cells
      are protected from the host's natural killer cells. No expression of human genes
      was observed after transplantation of human cord blood derived mononuclear cells
      (MNC) that were used as a negative control. In conclusion, we have shown that
      human cord blood somatic stem cells survive and are reprogrammed after
      transplantation into mouse livers, although a complete transdifferentiation to
      hepatocytes did not occur within 7 days, since some marker genes (GATA4 and alpha
      fetoprotein) were still negative. Switching off expression of beta2M may be part
      of an intriguing and novel mechanism explaining why stem cells escape the host's
      immune system.

PMID- 12074586
TI  - YlALK1 encoding the cytochrome P450ALK1 in Yarrowia lipolytica is
      transcriptionally induced by n-alkane through two distinct cis-elements on its
      promoter.
AB  - The YlALK1 gene, which encodes cytochrome P450ALK1, plays a primary role in the
      assimilation of n-decane by yeast Yarrowia lipolytica and is inducible by n
      decane at the transcriptional level. Deletion analysis of the YlALK1 promoter
      revealed that a 95-bp region on the YlALK1 promoter (from the position -400 to 
      304 upstream of the ATG codon) is essential for the induction by n-decane and we
      named this region ARR1 (alkane-responsive region). ARR1 was found to be made up
      of two different elements, ARE1 (alkane-responsive element 1; from -394 to -371)
      and ARE2 (from -325 to -305). By electrophoretic mobility shift assay, we found
      that the respective elements gave specific shift bands with the extracts from Y.
      lipolytica cells grown on n-alkane, but not much evidently from the cells grown
      on glycerol or glucose. This suggests that proteins that specifically bind to
      these elements are present and their binding or synthesis is dependent on n
      alkane.

PMID- 12074587
TI  - Restoration of TGF-beta regulation of plasminogen activator inhibitor-1 in Smad3
      restituted human choriocarcinoma cells.
AB  - Proliferation, migration, and invasiveness of the normal placental extravillous
      trophoblast (EVT) cells are negatively regulated by transforming growth factor
      beta (TGF-beta), whereas malignant EVT (JAR and JEG-3 choriocarcinoma) cells are
      resistant to TGF-beta. These malignant cells were found to have lost the
      expression of Smad3. Present study examined whether Smad3 restitution in JAR
      cells could restore TGF-beta response. We produced a stable Smad3 cDNA
      transfected clone (JAR-smad3/c) which exhibited further upregulation of Smad3 in
      the presence of TGF-beta1. Since anti-invasive effects of TGF-beta in the normal
      EVT cells were shown to be mediated in part by plasminogen activator inhibitor-1
      (PAI-1) and urokinase-type plasminogen activator (uPA), we compared the
      expression of PAI-1 and uPA in the normal EVT, JAR, and JAR-smad3/c cells in the
      presence or absence of TGF-beta1. The basal levels of PAI-1 mRNA and secreted PAI
      1 and uPA proteins were found to be very low in JAR and JAR-smad3/c cells, as
      compared to the normal EVT cells. However, TGF-beta1 upregulated PAI-1 and
      downregulated uPA in JAR-smad3/c cells, but not in JAR cells. Thus, resistance of
      choriocarcinoma cells to anti-invasive effects of TGF-beta may, at least in part,
      be due to loss of Smad3 expression.

PMID- 12074588
TI  - Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor
      protein with the TrkB tyrosine kinase receptor.
AB  - Brain-derived neurotrophic factor (BDNF) binds to and activates the TrkB tyrosine
      kinase receptor to regulate cell differentiation, survival, and neural plasticity
      in the nervous system. However, the identities of the downstream signaling
      proteins involved in this process remain unclear. Using a yeast two-hybrid screen
      with the intracellular domain (ICD-TrkB) of the TrkB BDNF receptor, we identified
      the Nck2 adaptor protein as a novel interaction partner of the active form of
      TrkB. Additionally, we identified three tyrosines in ICD-TrkB (Y694, Y695, and
      Y771) that are crucial for this interaction. Similar results were obtained for
      Nck1, an Nck2 homolog. We also found that TrkB could be co-precipitated with GST
      Nck2 recombinant protein or anti-Nck antibody in BDNF-activated cortical neurons.
      These results suggest that BDNF stimulation promotes interaction of Ncks with
      TrkB in cortical neurons.

PMID- 12074589
TI  - Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive
      nitrogen species donors.
AB  - Nitric oxide (*NO) and its by-products modulate many physiological functions of
      skeletal muscle including blood flow, metabolism, glucose uptake, and contractile
      function. However, growing evidence suggests that an overproduction of nitric
      oxide contributes to muscle wasting in a number of pathologies including chronic
      heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data
      point to the potential of inhibition various enzymes by reactive nitrogen species
      (RNS), including (.)NO and its downstream products such as peroxynitrite,
      primarily in purified systems. We hypothesized that exposure of skeletal muscle
      to RNS donors would reduce or downregulate activities of the crucial antioxidant
      enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344
      rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5
      mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM
      sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso
      acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1
      (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX,
      and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly
      lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX
      in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also
      resulted in a large and significant inhibition of total SOD and CAT. These data
      indicate that reactive nitrogen species impair antioxidant enzyme function in an
      RNS donor-specific and dose-dependent manner and are consistent with the
      hypothesis that excess RNS production contributes to skeletal muscle oxidative
      stress and muscle dysfunction.

PMID- 12074590
TI  - Role of CXC chemokines in the enhancement of LPS-induced neutrophil accumulation
      in the lung of mice by dexamethasone.
AB  - Lipopolysaccharide (LPS)-induced multiple organ injury was mediated in part by a
      transcription factor, nuclear factor-kappaB (NF-kappaB). Mice were pretreated
      with dexamethasone (DEX), an inhibitor of NF-kappaB activation, to elucidate its
      effects on LPS-induced early responses in vivo. Early responses measured 1 h
      after intraperitoneal LPS administration at a dose of 1 mg/kg were (1) neutrophil
      accumulation in the tissues, (2) neutrophil degranulation, and (3) protein and
      mRNA expressions of tumor necrosis factor-alpha (TNF-alpha) and ELR(+) CXC
      chemokines [macrophage inflammatory protein-2 (MIP-2) and cytokine-induced
      neutrophil chemoattractant (KC)]. Treatment with DEX before LPS administration
      suppressed NF-kappaB activation and plasma TNF-alpha levels almost to
      undetectable levels, but enhanced neutrophil accumulation and augmented MIP-2
      levels in the lung. The suppression of plasma TNF-alpha levels by pretreatment
      with an anti-TNF-alpha antibody did not enhance LPS-induced neutrophil
      accumulation in the lung. These results demonstrate that the enhancement of LPS
      induced neutrophil accumulation by DEX might be mediated by MIP-2 and not by TNF
      alpha.

PMID- 12074591
TI  - Dual regulation of phospholipase D1 by protein kinase C alpha in vivo.
AB  - The regulation of phospholipase D1 (PLD1), which has been shown to be activated
      by protein kinase C (PKC) alpha, was investigated in the human melanoma cell
      lines. In G361 cell line, which lacks PKCalpha, 12-O-tetradecanoylphorbol-13
      acetate (TPA)-induced PLD activation was potentiated by introducing PKCalpha by
      the adenovirus vector. The kinase-negative PKCalpha elevated TPA-induced PLD
      activity less significantly than the wild type. A PKC specific inhibitor
      GF109203X lowered PLD activation in the cells expressing PKCalpha, but did not
      prevent PLD potentiation induced by the kinase-negative PKCalpha. Expression of
      PKCbetaII and the kinase-negative PKCbetaII enhanced TPA-stimulated PLD activity
      moderately in MeWo cell line, in which PKCbetaII is absent. Furthermore, the TPA
      treatment increased the association of PKCalpha, PKCbetaII, and their kinase
      negative mutants with PLD1 in melanoma cells. These results indicate that PLD1 is
      dually regulated through phosphorylation as well as through the protein-protein
      interaction by PKCalpha, and probably by PKCbetaII, in vivo.

PMID- 12074592
TI  - Mutation of macrophage colony stimulating factor (Csf1) causes osteopetrosis in
      the tl rat.
AB  - Osteopetrosis results from a heterogeneous group of congenital bone diseases that
      display inadequate osteoclastic bone resorption. We recently mapped tl
      (toothless), a mutation that causes osteopetrosis in rats, to a genetic region
      predicted to include the rat Csf1 gene. In this study, we sequenced the coding
      sequence of the rat Csf1 gene to determine if a mutation in Csf1 could be
      responsible for the tl phenotype. Sequencing revealed a 10-base insertion in the
      coding sequence of mutant animals that produces a frameshift and generates a stop
      codon early in the mutant Csf1 coding sequence. The 41 amino acid polypeptide
      predicted to be produced from the Csf1 promoter would have only the first nine
      amino acids of the wild-type rat protein. These data suggest that osteopetrosis
      develops in tl/tl rats because they cannot produce functional mCsf, a growth
      factor required for osteoclast differentiation and activation.

PMID- 12074593
TI  - Gene expression profile analysis of rheumatoid synovial fibroblast cultures
      revealing the overexpression of genes responsible for tumor-like growth of
      rheumatoid synovium.
AB  - To elucidate the aberrant growth properties of rheumatoid synoviocytes, we have
      examined the gene expression profile of rheumatoid synovial fibroblasts (RSFs)
      and compared with that of normal synovial fibroblasts (NSF). Gene expression
      profile analysis was conducted with synoviocyte cultures obtained from five
      rheumatoid arthritis (RA) patients and five control cases using a commercial cDNA
      array containing the defined 588 cancer-related genes. The results were confirmed
      by real-time RT-PCR. Gene expression levels for the platelet-derived growth
      factor receptor alpha (PDGFRalpha), plasminogen activator inhibitor-1 (PAI-1),
      and stromal cell derived factor 1A (SDF1A) are constitutively augmented in RSF
      compared with NSF. The mRNA levels of PDGFRalpha, PAI-1, and SDF1A in RSF over
      NSF were 4.6-, 14-, and 2.8-fold, respectively, by real-time RT-PCR. In fact, we
      found that RSFs showed greater sensitivity to the cell proliferative effect of
      PDGF. T his aberrant gene expression profile suggests that RSF may have retained
      the premature phenotype of primordial synoviocytes.

PMID- 12074594
TI  - Dysfunction of rat liver mitochondria by selenite: induction of mitochondrial
      permeability transition through thiol-oxidation.
AB  - Selenium is an essential trace element in mammals and is thought to play a
      chemopreventive role in human cancer, possibly by inducing tumor cell apoptosis.
      Mitochondria play a pivotal role in the induction of apoptosis in many cell
      types. The effects of selenite on mitochondrial function were therefore
      investigated. Selenite induced the oxidation and cross-linking of protein thiol
      groups, mitochondrial permeability transition (MPT), a decrease in the
      mitochondrial membrane potential, and the release of cytochrome c in mitochondria
      isolated from rat liver. Induction of the MPT by selenite was prevented by
      cyclosporin A, EGTA, or N-ethylmaleimide. These results thus indicate that
      selenite induces the MPT as a result of direct modification of protein thiol
      groups, resulting in the release of cytochrome c and a loss of mitochondrial
      membrane potential.

PMID- 12074595
TI  - Keratin degradation: a cooperative action of two enzymes from Stenotrophomonas
      sp.
AB  - A novel keratin-degrading bacterium Stenotrophomonas sp. strain D-1, isolated
      from deer fur, produced two types of extracellular proteins: proteolytic and
      disulfide bond-reducing. The results on the biochemical properties suggest that
      this protease belongs to the serine protease, and the disulfide bond-reducing
      protein could be the disulfide reductase type. None of these enzymes showed
      keratinolytic activity independently. However, after mixing of the two enzymes,
      the keratinolytic activity was increased tremendously (more than 50-fold) over
      that of the protease only. This keratinolytic activity was more than 2-fold
      higher than that of the combination with proteinase K (also known for its high
      keratinolytic activity). Since the two enzymes discovered in this study acted
      cooperatively and resulted in higher keratinolytic activity, a new mechanism of
      keratin degradation has been revealed. To our knowledge, this is the first report
      on the cooperative action of two enzymes resulting in the effective degradation
      of keratin.

PMID- 12074597
TI  - Binding of the mammalian homolog of the Drosophila discs large tumor suppressor
      protein to the ribosome receptor.
AB  - DLG, the mammalian homolog of the Drosophila Discs Large suppressor protein,
      functions as a scaffolding protein that facilitates the transmission of diverse
      downstream signals. In the present study, we attempted to identify partner
      proteins for DLG, and found that DLG interacts through its PDZ domains with the
      ribosome receptor. The ribosome receptor is an integral endoplasmic reticulum
      protein that has been suggested to be involved in secretion. Our finding raises
      the possibility that DLG plays a role in the regulation of secretion by
      interacting with the ribosome receptor.

PMID- 12074596
TI  - The Gef1 protein of Saccharomyces cerevisiae is associated with chloride channel
      activity.
AB  - The Gef1 protein of the yeast Saccharomyces cerevisiae (Gef1p) has amino acid
      homology to the voltage-gated CLC chloride channel family. It has been postulated
      that it provides the compensatory transport of Cl- anions to the lumen of the
      Golgi thereby regulating the pH of this compartment. Using GEF1 fusion with
      heterologous promoter we obtained a yeast strain highly overproducing Gef1p. The
      electrophysiological properties of the microsomal fraction obtained from this
      strain were measured using lipid bilayer system. Our data indicate that Gef1p is
      associated with the chloride channel activity. This anion-selective channel has a
      unitary conductance of 42 pS when measured in symmetrical 600/600 mM TEA-Cl
      solutions, is voltage-dependent, and closes at high negative voltages.

PMID- 12074598
TI  - PAI-1 promotes extracellular matrix deposition in the airways of a murine asthma
      model.
AB  - Dysregulation of matrix metalloproteinases (MMPs) and ineffective fibrinolysis
      are associated with the deposition of extracellular matrix (ECM). We hypothesized
      that elevated plasminogen activator inhibitor (PAI)-1 promotes ECM deposition in
      the asthmatic airway by inhibiting MMP-9 activity and fibrinolysis. Degree of
      airway inflammation was similar in PAI-1(-/-) and wild type (WT) mice after
      ovalbumin (OVA) challenge. PAI-1 production, deposition of collagen and fibrin,
      and MMP-9 activity in the lung tissue or airways were greater after OVA challenge
      compared with saline challenge. However, in PAI-1(-/-) mice, collagen deposition
      was 2-fold less, fibrin deposition was 4-fold less, and MMP-9 activity was 3-fold
      higher. This is the first direct evidence that the plasmin system regulates ECM
      deposition in the airways of a murine asthma model, independently of the effect
      of PAI-1 on inflammatory cells. The results suggest that the PAI-1-dependent
      inhibition of MMP-9 activity and fibrinolysis is a major mechanism by which ECM
      deposition occurs.

PMID- 12074599
TI  - Effects of oral vitamin C on monocyte: endothelial cell adhesion in healthy
      subjects.
AB  - Monocyte recruitment and retention in the vasculature is influenced by oxidative
      stress and is involved in cardiovascular disease (CVD). Individuals with low
      plasma ascorbate are at elevated risk of CVD. It is unknown whether vitamin C
      supplementation affects monocyte adhesion to endothelial cells (ECs) in healthy
      non-smokers. In a randomised double-blind crossover study the effect of vitamin C
      supplementation (six weeks, 250 mg/day) was determined in subjects with normal
      (HIC) and below average (LOC) plasma vitamin C concentration at baseline (mean=67
      microM, n=20, mean=32 microM, n=20, respectively). LOC subjects showed 30%
      greater monocyte adhesion to ECs. This was significantly reduced by 37% (P<0.02)
      following vitamin C supplementation to levels of HIC monocyte adhesion. No
      differences in plasma malondialdehyde concentrations were observed between groups
      or after supplementation. In conclusion, vitamin C supplementation normalises
      monocyte adhesion in subjects with low plasma vitamin C (LOC). This process may
      be related to a direct effect on monocytes, independent of lipid peroxidation.

PMID- 12074600
TI  - Cloning and characterization of a novel human gene RNF38 encoding a conserved
      putative protein with a RING finger domain.
AB  - RING finger (C3HC4-type zinc finger) is a variant zinc finger motif present in a
      large family of functionally distinct proteins. We describe the cloning and
      characterization of a novel human transcript RNF38 encoding a new member of the
      RING finger protein family. The complete mRNA consists of about 6.8 kb widely
      expressed in human tissues as a single transcript, most abundantly in testis. The
      predicted proline-rich protein consists of 432 amino acid residues with a coiled
      coil motif and a RING-H2 motif (C3H2C2) at its carboxy-terminus. High degree
      homology was found between the human protein and hypothetical peptides from
      several other species including Rattus norvegicus, Mus musculus, and Drosophila
      melanogaster, indicating a significant conservation throughout evolution. The
      RNF38 genomic structure was determined and comprises at least 13 exons extending
      over more than 65 kb in the genome, 78 kb centromeric to the GNE gene on human
      chromosome 9p12-p13. The involvement of this chromosomal segment in a large
      number of human diseases and in particular in various types of malignancies urges
      the assessment of the potential functional role of RNF38 in these disorders.

PMID- 12074602
TI  - Fibrillarin binds to a 3' cis-regulatory element in pre-mRNA of uvi15+ in fission
      yeast.
AB  - uvi15+ is induced by various stresses including exposure to UV-light. Previously,
      we demonstrated that the UV-induction is mainly regulated at the post
      transcriptional level through a cis-acting element in the pre-mRNA. Here we show
      that deletion analyses define an 18-nt element responsible for the UV-induction.
      RNA gel mobility shift assay showed that a specific protein(s) could form a
      complex with the 54-nt element but its binding ability is moderately decreased in
      response to UV-light. Using yeast three-hybrid screen, we isolated a homolog of
      fibrillarin as a protein interacting with the 54-nt element, which is a key
      nucleolar protein for pre-rRNA processing. We further showed that the recombinant
      fibrillarin specifically binds to the element in a sequence-specific manner.
      Thus, the data suggest that fission yeast fibrillarin might regulate uvi15+ mRNA
      stability via binding with the 54-nt element in the pre-mRNA, implying that
      fibrillarin is involved in both pre-mRNA and pre-rRNA processing.

PMID- 12074601
TI  - Cell death by pyruvate deficiency in proliferative cultured calvarial
      osteoblasts.
AB  - Cell survival was significantly decreased in primary cultured rat calvarial
      osteoblasts in vitro at Day 0, 1, and 3 by replacement of the standard culture
      medium (alpha-modified minimum essential medium; alpha-MEM) with Dulbecco's
      modified eagle's medium (DMEM). Decreased cell survival was also observed
      following medium replacement in cultures of murine calvaria-derived osteoblastic
      cell line MC3T3-E1. Staining with Hoechst33342 revealed apoptotic cells with
      fragmented or condensed nuclei, while a fraction of the cell culture was stained
      with propidum iodide, indicating necrosis. Marked increases in DNA binding of
      both activator protein-1 and nuclear factor-kappaB were found in nuclear extracts
      of cells following medium replacement. The addition of either pyruvate or
      cysteine at each concentration found in alpha-MEM almost entirely prevented cell
      death associated with medium replacement at Day 3. These results suggest that
      pyruvate and cysteine may be essential factors for cell growth and survival in
      osteoblast cultures at the proliferative phase.

PMID- 12074604
TI  - The Federation of European Societies for Surgery of the Hand: its birth and
      development-the first decade.

PMID- 12074605
TI  - Simultaneous toe-to-hand transfer and lower extremity amputations for severe
      upper and lower limb defects: the use of spare parts.
AB  - From 1995 to 2000, five microvascular toe-to-hand transfers were performed in
      three children who were simultaneously undergoing lower extremity amputations.
      Their ages at time of transfer ranged from 4 to 10 years and the types of lower
      extremity amputation included toe amputation, foot amputation and through-knee
      amputation. The resulting toe-to-hand transfers included three great toe-to-thumb
      transfers and one combined great and second toe-to-hand transfer. The toe-to-hand
      transfers were all successful and all the lower extremity amputations healed
      without complications. In all cases, improved hand function and lower extremity
      function was noted by the families. These unique cases represent the ultimate use
      of spare parts in congenital hand surgery.

PMID- 12074606
TI  - Effects of haemodilution and rewarming with regard to digital amputation in
      frostbite injury: an experimental study in the rabbit.
AB  - Peripheral vascular failure with haematological and haemodynamic changes occurs
      after frostbite injuries. In order to study the effects of normovolemic
      haemodilution on the extent of digital necrosis, the paws of rabbits were
      haemodiluted and frozen to -15 degrees C. Dextran or gelatin was used as the
      plasma substitute in two groups and the rewarming after the cold injury was
      performed either at room temperature (22 degrees C) or with hot water baths (38
      degrees C). The extent of necrosis was significantly less in the rabbits
      haemodiluted with dextran or gelatin and rewarmed in hot water baths.

PMID- 12074607
TI  - Glomus tumour of the hand.
AB  - We report a series of 18 patients with pain in the thumb or finger tips who were
      diagnosed as having glomus tumour. Fourteen patients were found to have
      histopathologically proven glomus tumours, one had a neuroma and three had
      haemangioma. The duration of symptoms before treatment averaged 1.9 years. Cold
      sensitivity and Hildreth's tests have sensitivities of 100% and 77.4%
      respectively and specificity of 100%. Love's pin test had a sensitivity of 100%.
      Love's and Hildreth's tests showed 78% accuracy, whereas the cold-sensitivity
      test was 100% accurate. We used a double-tourniquet technique during dissection
      and excision of the tumour. None of our patients experienced recurrence of
      symptoms during the post-operative follow up.

PMID- 12074608
TI  - The nerve supply of the trapeziometacarpal joint.
AB  - Ten forearm and hand specimens from fresh cadavers were dissected and examined
      under magnification for articular branches to the trapeziometacarpal joint
      arising from the thenar and palmar cutaneous branches of the median nerve, the
      superficial branch of the radial nerve and the lateral cutaneous nerve of
      forearm. In all but one specimen the thenar branch of the median nerve sent an
      articular branch to the trapeziometacarpal joint. Multiple branches from the
      palmar cutaneous branch of the median nerve, the superficial branch of the radial
      nerve and the lateral cutaneous nerve of forearm were also found. All these
      branches need to be divided during a "complete" denervation of the
      trapeziometacarpal joint.

PMID- 12074609
TI  - The relation between primary osteoarthritis of the trapeziometacarpal joint and
      supernumerary slips of the abductor pollicis longus tendon.
AB  - We have studied whether accessory abductor pollicis longus slips inserting into
      the thenar eminence or trapezium influence the incidence and severity of
      trapeziometacarpal joint osteoarthritis. The right first extensor compartment of
      73 cadavers was dissected and trapeziometacarpal degeneration was graded
      macroscopically. The main abductor pollicis longus tendon which inserted at the
      metacarpal base was accompanied by supernumerary APL slips in 96% of cases.
      Thenar or trapezial slips occurred frequently but coexisted in only one case. The
      incidence of trapeziometacarpal arthritis was not influenced by the number of
      accessory slips or whether they inserted onto the thenar eminence or the
      trapezium.

PMID- 12074610
TI  - Compartment reconstruction for De Quervain's disease.
AB  - A new surgical treatment for De Quervain's disease is presented, in which the
      anatomy and function of the first dorsal compartment is preserved. Our findings
      in 11 wrists in ten patients revealed complete relief of the pre-operative
      symptoms in all instances. The advantages of this technique are its ease, its
      restoration of normal anatomy, and the prevention of tendon prolapse.

PMID- 12074611
TI  - Management of acute fractures and nonunions of the proximal pole of the scaphoid.
AB  - It is my belief that all acute proximal pole fractures should be treated by open
      reduction and internal fixation, via a dorsal approach. There is no longer any
      place for conservative treatment of these fractures, because a lengthy period of
      plaster immobilization is required and there is an unacceptably high risk of
      nonunion with conservative management. Unfortunately, nonunion of the proximal
      pole remains a common and disabling problem which demands careful evaluation and
      treatment. Internal fixation combined with limited cancellous bone grafting
      produces very satisfactory results in terms of pain relief and function, and
      clinical results are as good as those reported for more complex procedures
      involving vascularized grafts and prolonged cast immobilization. While the place
      for vascularized grafting has yet to be clearly defined, at present it is a
      technique which should be reserved for cases with long-standing ischaemia or
      failed previous surgery.

PMID- 12074612
TI  - Duplicated longitudinal bracketed epiphysis 'kissing delta phalanx' in the hand.
AB  - The duplicated longitudinal bracketed epiphysis ("kissing delta") phalanx has
      been described rarely. These delta bones have a bizarre appearance and are often
      associated with other developmental abnormalities such as central polydactyly. We
      have seen a total of 13 kissing delta phalanges in the hands. We discuss their
      natural history, look at the associated anomalies and consider the treatment
      options for this very rare congenital anomaly.

PMID- 12074613
TI  - Arthroscopy of the proximal interphalangeal joints of the finger.
AB  - Cadaveric studies were carried out to evaluate the technique, portals and
      possible indications for arthroscopy of the proximal interphalangeal joints of
      the finger. We suggest horizontal placement of the hand instead of using a
      traction tower, as it is important to be able to flex the joint freely. The
      recommended arthroscopic portals are either between the central slip and the
      lateral bands of the extensor mechanism or between the lateral band and the
      collateral ligament. A blunt technique of introduction is used to avoid
      iatrogenic cartilage damage and possible digital nerve injury.

PMID- 12074614
TI  - Hyaluronidase versus surgical excision of ganglia: a prospective, randomized
      clinical trial.
AB  - This prospective, randomized clinical trial compared the treatment of ganglia by
      either hyaluronidase injection and aspiration or surgical excision. Fifty
      patients were randomly allocated to each group and 46 patients in the
      hyaluronidase group and 43 in the surgical group were available for follow-up at
      1 year. Patients with ganglia treated with hyaluronidase had a recurrence rate of
      77%, which was significantly higher (P<0.01) than the recurrence rate after
      surgery (24%).

PMID- 12074615
TI  - Assessment of outcome of carpal tunnel syndrome: a comparison of
      electrophysiological findings and a self-administered Boston questionnaire.
AB  - The relationship between nerve conduction studies and the self-administered
      Boston Questionnaire that measures the severity of symptoms and functional status
      in carpal tunnel syndrome was assessed in 44 patients with idiopathic carpal
      tunnel syndrome. The patients were examined preoperatively and 3 and 6 months
      postoperatively. Although both the clinical outcome and electrophysiological
      findings improved significantly after surgery, we observed no correlation between
      improvements in nerve conduction and the questionnaire scores.

PMID- 12074616
TI  - Modified "on-top-plasty" technique for restoring length to amputation stumps.
AB  - Five patients were successfully treated with a modified "on-top-plasty"
      technique, in which a finger stump is lengthened by transfer of an adjacent
      amputation stump with a reverse blood flow fingerstump. This technique can be
      performed in the acute phase or as a secondary procedure. A conventional on-top
      plasty can be performed by transfer of a partially amputated index or ring finger
      to the "top" of the proximal phalanx of an amputated middle finger.
      Alternatively, the transferred part may be used in an intercalated fashion to
      reconstruct the middle phalanx, using a prosthesis to reconstruct the proximal
      interphalangeal joint. The results, complications and disadvantages of the
      technique are reported. We propose this procedure for the reconstruction of the
      middle ring finger when a free microneurovascular toe-to-hand transfer is
      contraindicated or refused by the patient.

PMID- 12074618
TI  - Thumb function without the abductor pollicis longus and extensor pollicis brevis.
AB  - Two patients are reported in which one thumb has lost the abductor pollicis
      longus and extensor pollicis brevis tendons. This is an uncommon injury in
      isolation, and these cases provide an opportunity to assess the functional
      importance of these musculotendinous units.

PMID- 12074617
TI  - The effect of steroids on Dupuytren's disease: role of programmed cell death.
AB  - This study compared the rates of proliferation and apoptosis of cells within
      nodules of Dupuytren's disease and nodules from patients that had been injected
      preoperatively with steroid (Depo-Medrone). It also compared the effects of
      steroids in apoptosis in cultured Dupuytren's cells and control fibroblasts from
      palmar fascia and fascia lata. Steroids reduced the rate of fibroblast
      proliferation and increased the rate of apoptosis of both fibroblasts and
      inflammatory cells in Dupuytren's tissue. Steroids also produced apoptosis of
      cultured Dupuytren's cells but not of palmar fascia and fascia lata cells.

PMID- 12074619
TI  - The role of human-derived fibrin sealant in the reduction of postoperative flexor
      tendon adhesion formation in rabbits.
AB  - This study assessed the role of a novel fibrin sealant (Vivostat in adhesion
      reduction after flexor tendon surgery. The deep flexor tendons of the 2nd and 4th
      digits of the left paw of 20 rabbits were exposed and a standard partial injury
      was performed on each. The rabbits were randomized to either immediate post
      injury treatment with Vivostat or no treatment. In each case active movement of
      the 2nd digit was prevented while the 4th digit was allowed to move normally. The
      two groups were assessed at 14 days for adhesion formation with a tensiometer.
      The right paw acted as the unoperated control. Results showed that there was no
      significant difference in the force needed to remove the tendon from its sheath
      when comparing the two Vivostat((R))-treated groups to the unoperated controls.
      There was, however, a highly significant difference in this force between the non
      Vivostat-treated groups and the unoperated controls. This suggests a beneficial
      effect of Vivostat in reducing post surgical tendon adhesion formation.

PMID- 12074620
TI  - A prospective, controlled, randomized trial comparing early active extension with
      passive extension using a dynamic splint in the rehabilitation of repaired
      extensor tendons.
AB  - This prospective, randomized, controlled trial compared two methods of
      rehabilitating extensor tendon repairs in zones IV-VIII. Group A patients
      followed an early active mobilization regimen and Group B patients followed a
      dynamic splintage regimen. Data on 19 patients in Group A and 17 patients in
      Group B were collected at 4 weeks and at final follow-up (3 months median follow
      up for both groups). Extension lag, flexion deficit and total active motion (TAM)
      were measured. At 4 weeks, patients in Group B had a better TAM (median 87%,
      range 56-102%) compared to patients in Group A (median 77%, range 52-97%). At
      final follow-up, there were no significant differences in the results of the two
      groups. There were no ruptures in either group.

PMID- 12074621
TI  - Metacarpal descent, definition and normal range.
AB  - Metacarpal descent, an indication of carpometacarpal (CMC) joint mobility, was
      measured in 90 normal subjects by assessing the alignment of the metacarpal heads
      with the hand in a relaxed posture and when making a tight fist. Metacarpal
      descent was greater in women. Hand dominance was associated with an increase in
      positional angles but not metacarpal descent.

PMID- 12074622
TI  - Callus resection for brachial plexus compression following stress-induced first
      rib fracture.
AB  - A 27-year-old man presented with a lower trunk brachial plexus injury due to
      excessive callus formation following a stress-induced first rib fracture. The
      callus, but not the first rib, was resected through a supraclavicular approach.
      His symptoms resolved in 2 months, and no recurrence was seen at 2 years follow
      up.

PMID- 12074623
TI  - Type 5 avulsion of the insertion of the flexor digitorium profundus tendon.

PMID- 12074626
TI  - Acute effect of exercise-induced leg ischemia on cutaneous vasoreactivity in
      patients with stage II peripheral artery disease.
AB  - Conflicting data are available regarding the acute effect of exercise-provoked
      leg ischemia on the endothelial function in patients with stage II peripheral
      artery disease (PAD). In order to clarify this issue, cutaneous hyperemic
      responses to iontophoresis delivery of an endothelium-dependent (acetylcholine,
      ACh) and an endothelium-independent (sodium nitroprusside, SNP) vasodilator were
      evaluated under resting conditions, and before and after a treadmill test, using
      laser Doppler flowmetry, in 14 males (aged 68 +/- 4 years) affected by stage II
      PAD; 14 age-matched healthy males served as controls. At resting, a significantly
      reduced skin hyperemic response to ACh and to SNP was observed in PAD patients
      when compared to controls. Following treadmill, the leg skin hyperemic response
      to ACh delivery was significantly lower at peak of claudication than prior
      exercise (139 +/- 10 vs 213 +/- 25%, P = 0.01) in PAD patients, whereas no
      difference was observed in controls. The hyperemic response to SNP after exercise
      did not differ from baseline in either PAD patients or controls. The present data
      are in keeping with a reduced skin vasodilator capacity in stage II PAD patients
      at resting. In addition, the further impairment of skin endothelium-dependent
      vasodilation at the peak of claudication could indicate an acute endothelial
      dysfunction associated with exercise-induced leg muscle ischemia. These
      preliminary results also suggest that the threshold of claudication should not be
      exceeded during rehabilitation programs for PAD patients.

PMID- 12074625
TI  - Inside-out cannulation of fine lymphatic trunks used to quantify coupling between
      transsynovial flow and lymphatic drainage from rabbit knees.
AB  - The coupling of periarticular lymph flow to transsynovial flow from a joint
      cavity, i.e., fluid load, is essential to avoid periarticular edema, which is
      associated with arthritic morning stiffness. To study coupling in swollen joints,
      a new method, "inside-out" cannulation, which eliminates dead space, resistance
      and cutout, was used to collect lymph from fine femoral lymph trunks in
      anesthetised rabbits while the knee joint cavity was infused with Evans blue
      albumin (EVA) at controlled intraarticular pressure and transsynovial drainage
      rates. The amount of joint lymph in femoral lymph (volume fraction V(v)) was
      calculated by EVA analysis. Joint lymph flow and EVA clearance was 1.5 +/- 0.4
      microl min(-1) (mean +/- SEM, n = 62) at mean trans-synovial flow, 23 microl min(
      1), and increased with pressure. Volume fraction increased from 16% at 10 cmH(2)O
      to 43% at 41 cmH(2)O. The increase in lymph flow with pressure, 0.052 +/- 0.025
      microl min(-1) cmH(2)O(-1) (n = 61) was much smaller than the increase in
      transsynovial flow (periarticular fluid load) with pressure, 0.71 +/- 0.14 microl
      min(-1) cmH(2)O(-1) (P < 0.001). Their ratio, the coupling coefficient, was only
      0.06-0.11. Thus, although up to 43% of femoral lymph could stem from a single
      swollen joint, this drained away only a small fraction of the transsynovial
      filtrate. The study showed that joint lymphatic drainage is coupled to joint
      pressure and transsynovial flow; but the coupling is insufficient to prevent
      periarticular fluid accumulation under conditions of joint volume expansion and
      limb immobility. This may contribute to the periarticular edema of arthritis.

PMID- 12074627
TI  - Similar permeability responses to nitric oxide synthase inhibitors of venules
      from three animal species.
AB  - The influence of nitric oxide (NO) on microvascular permeability remains unclear.
      NO synthase (NOS) inhibitors have been reported to increase as well as to
      decrease permeability in different experimental models and animal species. We
      tested the hypothesis that NOS inhibitors influence venular permeability
      differently in amphibians and mammals. Permeability coefficients to albumin
      (P(alb)(s)) were measured on in situ mesenteric venules of the frog and rat and
      excised pig coronary venules before and after exposure to NOS inhibitors. Despite
      individual variability in magnitude of responses, NOS inhibitors resulted in a
      reduction in P(alb)(s) in each species. Superfusion with 10(-5) M N(G)-monomethyl
      l-arginine (l-NMMA) reduced P(alb)(s) of frog mesenteric venules by 42% (from a
      median of 11.4 x 10(-7) cm s(-1), n = 12, P < 0.01) and by 67% in porcine
      coronary venules (from 12.5 x 10(-7) cm s(-1), n = 5, P < 0.05). The response was
      attenuated in rat mesenteric venules; 10(-4) M N(G)-nitro-l-arginine methyl ester
      (l-NAME) reduced P(alb)(s) by 23% (from 7.6 x 10(-7) cm s(-1), n = 9, P = 0.01).
      The inactive d-enantiomers of the NOS inhibitors were without effect on P(alb)(s)
      in each model. In pig venules, perfusion with blood modified the permeability
      responses to l-NMMA, suggesting that effects of NO on permeability are modified
      by one or more elements of blood. These data support a role of nitric oxide
      release on venular permeability to albumin that is conserved among the three
      animal species.

PMID- 12074628
TI  - Blood flow does not correlate with the size of metastasis in our new intravital
      observation model of Lewis lung cancer.
AB  - We previously reported a novel in situ observation model for microcirculation of
      lung metastasis from subcutaneously implanted Lewis lung cancer into mouse. Using
      this model, we studied the correlation of blood flow and the size of lung
      metastasis. It was revealed that metastatic growth and its angiogenesis are
      suppressed by circulating angiogenesis inhibitors, such as angiostatin or
      endostatin, released from primary tumor. When we removed the primary tumor, the
      metastasized lung cancer significantly grew faster and larger. But the blood flow
      per area did not increase either inside or outside of the metastatic tumor. This
      suggests that the growth of metastatic tumor is directly regulated not by blood
      flow increase but by the other effects of the circulating factors.

PMID- 12074629
TI  - Modulation of microvascular signaling by heparan sulfate matrix: studies in
      syndecan-4 transgenic mice.
AB  - The onset of tissue ischemia is associated with significant changes in the
      expression of heparan sulfate- (HS) carrying core proteins that, in turn, lead to
      alterations in composition of the extracellular HS matrix. Since HS can bind
      numerous growth factors and cytokines, such changes in the HS matrix content can
      have profound effects on the ability of these factors to interact with their
      target cells. To investigate the role of increased HS matrix content on
      microvascular function, we used alpha-myosin heavy chain (MHC) promoter to
      overexpress a HS-carrying core protein, syndecan-4, in cardiac myocytes in mice.
      Mice expressing the transgene (alpha MHC-S4) demonstrated a significant increase
      in nitric oxide (NO) release in the coronary effluent in response to fibroblast
      growth factor 2 (FGF2, 1 microg/mL) administration despite similar expression
      levels of NO synthase genes II and III (iNOS and eNOS, respectively). In vitro
      studies of coronary microvessels derived from alpha MHC-S4 mice demonstrated
      increased relaxation response to FGF2 compared to control mice. At the same time,
      vasodilator response to adenosine diphosphate (ADP) was significantly impaired in
      alpha MHC-S4 mice-derived microvessels. Addition of exogenous HS to microvessels
      derived from control mice enhanced FGF2-induced vasodilation while inhibiting ADP
      induced vasomotion. The vasomotor activity of the endothelial receptor
      independent agent (A23187) and the endothelium-independent agent (sodium
      nitroprusside) was not affected by heparan sulfate. These results demonstrate
      that alterations in HS production have a profound and heterogeneous effect on
      endothelial receptor-dependent vasodilators and point to a novel role of the HS
      matrix in regulation of microvascular homeostasis.

PMID- 12074630
TI  - Focal adhesion molecules expression and fibrillin deposition by lymphatic and
      blood vessel endothelial cells in culture.
AB  - The microfibrils of anchoring filaments, a typical ultrastructural feature of
      initial lymphatic vessels, consist mainly of fibrillin and are similar to the
      microfibrils of elastic fibers. As we previously demonstrated, they radiate from
      focal adhesions of lymphatic endothelium to the perivascular elastic network.
      Although present in large blood vessels, fibrillin microfibrils have never been
      detected in blood capillaries. Here we report immunohistochemical evidence that
      cultured bovine aortic and lymphatic endothelial cells express fibrillin
      microfibrils. These microfibrils form an irregular web in lymphatic endothelial
      cells, whereas in blood vessel endothelial cells they are arranged in a honeycomb
      pattern. Cultured lymphatic and blood vessel endothelial cells also produce focal
      adhesion molecules: focal adhesion kinase, vinculin, talin, and cytoskeletal beta
      actin. Our data suggest that anchoring filaments of initial lymphatic vessels in
      vivo may be produced by endothelium. Through their connection with focal
      adhesions, they may form a mechanical anchorage for the thin wall of initial
      lymphatic vessels and a transduction device for mechanical signals from the
      extracellular matrix into biochemical signals in endothelial cells. The complex
      anchoring filaments-focal adhesions may control the permeability of lymphatic
      endothelium and finely adjust lymph formation to the physiological conditions of
      the extracellular matrix. The different deposition of fibrillin microfibrils in
      blood vessel endothelial cells may be related to the necessity of withstanding
      shear forces. Thus, in our opinion, differences in fibrillin deposition imply a
      different role of fibrillin in blood vessel and lymphatic endothelium.

PMID- 12074631
TI  - Blockade of P-selectin does not affect reperfusion injury in hamsters subjected
      to glutathione inhibition.
AB  - P-selectin antibody has been shown to prevent microvascular damage after ischemia
      reperfusion (I/R). We investigated whether the treatment with anti-P-selectin
      would attenuate the decrease in capillary perfusion after glutathione (GSH)
      inhibition in hamster cheek pouch microcirculation subjected to I/R. Animals were
      treated for 3 days with l-buthionine-[S,R]-sulfoximine (BSO) to inhibit GSH
      synthesis. P-selectin expression was determined by using an in situ
      immunofluorescence method in the microvessels. Ischemia was induced by clamping
      the cheek pouch for 30 min followed by 30 min of reperfusion. Changes in
      capillary perfusion, RBC velocity, and leukocyte and platelet adhesion on
      microvessels were measured after I/R. Hamsters subjected to I/R showed increased
      leukocyte and platelet adhesion as well as decreased capillary perfusion. The
      anti-P-selectin group showed a significant P-selectin expression, that occurs at
      the venular bifurcations within 15-30 min of reperfusion, as well as no increase
      in leukocyte and platelet adhesion on microvessels. BSO partially prevented P
      selectin expression but the decrease in capillary perfusion and the increase in
      both platelet and leukocyte adhesion in microvessels were greater. GSH
      significantly prevented P-selectin expression as well as capillary perfusion
      decrease after I/R. In conclusion, GSH inhibition blunted the protective effects
      of anti-P-selectin treatment with marked leukocyte adhesion on postcapillary
      venules and platelet-endothelial cell interactions in arterioles and venules and
      decreased capillary perfusion at reperfusion, thus suggesting that the mechanism
      of I/R injury is not critically dependent on P-selectin.

PMID- 12074632
TI  - Ultrastructural and morphometric comparison of retinal and myocardial capillaries
      following acute ischaemia.
AB  - The recovery of any tissue following a period of ischaemia is dependent on a
      patent microvasculature to restore blood flow. In the ischaemic myocardium, a
      reduction in capillary cross-sectional dimensions occurs, which is likely to
      contribute to "no-reflow" injury. Clinical and experimental evidence indicates
      that the retina is able to tolerate moderate periods of ischaemia without
      significant loss of function. The aim of the present study is to test the
      hypothesis that, as an end-arterial system, the retina possesses compensatory
      processes to maintain a functional microcirculation following acute ischaemia.
      Thirty minutes of no-flow global ischaemia was induced in isolated hearts of
      Wistar rats without reperfusion. The retina was also made ischaemic for 30 min
      using two experimental models: microsphere embolization and anoxic superfusion.
      Changes in capillary dimensions were assessed by ultrastructural morphometry.
      Following 30 min of myocardial ischaemia capillaries appeared swollen with a
      significant reduction in total capillary and luminal cross-sectional area. By
      contrast, ischaemic retinal capillaries showed minimal morphological changes and
      no significant alteration in dimensions. We have demonstrated notable differences
      in the response of retinal and myocardial microvessels to acute ischaemia. It is
      likely that the maintenance of capillary patency following short periods
      ischaemia in the retina is part of an adaptive mechanism to protect visual
      function.

PMID- 12074633
TI  - Retinal blood flow during hyperoxia in humans revisited: concerted results using
      different measurement techniques.
AB  - Retinal vasculature shows pronounced vasoconstriction in response to hyperoxia,
      which appears to be related to the constant oxygen demand of the retina. However,
      the exact amount of blood flow reduction and the exact time course of this
      phenomenon are still a matter of debate. We set out to investigate the retinal
      response to hyperoxia using innovative techniques for the assessment of retinal
      hemodynamics. In a total of 48 healthy volunteers we studied the effect of 100%
      O(2) breathing on retinal blood flow using two methods. Red blood cell movement
      in larger retinal veins was quantified with combined laser Doppler velocimetry
      and retinal vessel size measurement. Retinal white blood cell movement was
      quantified with the blue field entoptic technique. The time course of retinal
      vasoconstriction in response to hyperoxia was assessed by continuous vessel size
      determination using the Zeiss retinal vessel analyzer. The response to hyperoxia
      as measured with combined laser Doppler velocimetry and vessel size measurement
      was almost twice as high as that observed with the blue field technique.
      Vasoconstriction in response to 100% O(2) breathing occurred within the first 5
      min and no counterregulatory or adaptive mechanisms were observed. Based on these
      results we hypothesize that hyperoxia-induced vasoconstriction differentially
      affects red and white blood cell movement in the human retina. This hypothesis is
      based on the complex interactions between red and white blood cells in
      microcirculation, which have been described in detail for other vascular beds.

PMID- 12074634
TI  - The Thy-1/Thy-1 ligand interaction is involved in binding of melanoma cells to
      activated Thy-1- positive microvascular endothelial cells.
AB  - The expression of adhesion molecules on endothelial cells as well on tumor cells
      regulates and directs adhesion and transmigration of tumor cells through the
      endothelial cell barrier as one prerequisite to the formation of metastasis. Thy
      1 is an inducible activation-associated cell-adhesion molecule on human dermal
      microvascular endothelial cells (HDMECs). In this study we investigated whether
      the Thy-1/Thy-1 ligand interaction may also play a role in adhesion of melanoma
      cells to endothelial cells. In situ, a strong Thy-1 expression on endothelial
      cells in melanoma and melanoma metastases was observed. In vitro, Thy-1
      expression was stimulated by melanoma-cell-derived soluble factors, reflecting
      that Thy-1 expression in melanoma is not only due to a nonspecific inflammatory
      response. TNFalpha and bFGF were not responsible for this effect. In vitro and in
      situ a Thy-1 ligand was detected on melanoma cells. In cell-adhesion assays we
      showed the involvement of the Thy-1/Thy-1 ligand interaction in adhesion of
      melanoma cells to HDMECs. In summary, the data support that the study of the Thy
      1/Thy-1 ligand interaction might give a more detailed insight into the regulation
      and direction of adhesion of melanoma cells to endothelial cells as one critical
      step in the formation of tumor metastasis.

PMID- 12074635
TI  - Prostaglandin E(1) protects human liver sinusoidal endothelial cell from
      apoptosis induced by hypoxia reoxygenation.
AB  - Hepatic ischemia-reperfusion injury is an important cause of graft dysfunction
      after liver transplantation. Liver sinusoidal endothelial cells (LSECs) are
      particularly sensitive to ischemia-reperfusion injury and undergo apoptosis. This
      study investigates the protective role of PGE(1) on apoptosis of LSEC during
      hypoxia-reoxygenation in vitro. Hypothermia-hypoxia followed by reoxygenation
      triggered LSEC apoptosis, and prostaglandin PGE(1) protected LSEC from apoptosis
      in a dose-dependent manner. The release of matrix metalloproteinases (MMPs) and
      nitric oxide (NO) by LSECs were increased after hypoxia reoxygenation. Both the
      MMP inhibitor BB3103 and the NO inhibitor LNAM effectively decreased LSEC
      apoptosis, suggesting a separate role of MMPs and NO in hypoxia-reoxygenation
      induced LSEC apoptosis. PGE(1) down-regulated NO production by inhibiting the
      expression of inducible NO synthase in LSEC. PGE(1) also inhibited MMP-2 release
      from LSEC during hypoxia reoxygenation. These results indicate that the
      protection of LSECs from apoptosis by PGE(1) in hepatic ischemia-reperfusion
      injury is mediated by inhibiting inducible NO synthase and MMP release.

PMID- 12074636
TI  - Parametric imaging of tumor perfusion with deuterium magnetic resonance imaging.
AB  - Imaging of the vasculature and its functioning over the entire lesion may
      significantly aid in cancer diagnosis, assessment of prognosis, and therapeutic
      evaluation. In the current study we present a dynamic three-dimensional deuterium
      magnetic resonance imaging method that determines the intravascular volume
      fraction and water perfusion rate at a resolution of 2 mm(2)/pixel. The method
      was tested and utilized to characterize the vasculature of orthotopic MCF7 human
      breast cancer tumors in CD1-NU athymic mice. A new algorithm based on Patlak's
      kinetic model was developed to analyze the dynamic images acquired during and
      after termination of infusion with deuterated water. The resulting parametric
      maps spanned a wide range from 0.4 to 35.2% for the intravascular volume fraction
      and from 4 x 10(-6) to 3.9 x 10(-3) min(-1) for the perfusion rate and exhibited
      high intratumoral and intertumoral heterogeneity at both parameters. The
      intravascular volume fraction did not correlate with the corresponding perfusion
      rate, demonstrating the irregular outgrowth of tumor neovascularization.
      Averaging the data or analyzing at spatially degraded resolution completely
      masked the presence of both "hot spots" and hypoxic loci, highlighting the
      critical importance of high spatial resolution. The method is applicable to other
      types of tumors and animal models and may be extended to humans.

PMID- 12074637
TI  - Early pericyte response to brain hypoxia in cats: an ultrastructural study.
AB  - Hypoxic condition in the brain result in microvascular dysfunction. Pericytes are
      one of the blood-brain barrier constituents with the endothelial cells and
      astrocytes. Pericytes of blood-brain barrier are the first cells to react to
      hypoxia of brain. We showed, at the ultrastructural level, microvascular pericyte
      responses to the brain hypoxia in early stage of hypoxia in cats. In first 2 h of
      hypoxia, pericytes start to migrate and one of every three pericytes migrates
      from original location. In the first stage of migration spikes occur at the
      abluminal surface of pericytes. At the same time basal lamina thickens and
      endothelial cells remain the same.

PMID- 12074638
TI  - Capillary blood flow during severe hemodilution observed by a noninvasive
      transcutaneous technique using flash epi-illumination.
AB  - Capillary red blood cell (RBC) flow in the skin of rat tail during an extreme
      hemodilution with albumin was microscopically observed with a completely
      noninvasive transcutaneous technique using flash epi-illumination. This
      illumination with a filter (center wavelength, 550 nm) caused RBC to become
      darker and contrast well with the background tissue since the light was absorbed
      by hemoglobin inside the RBC. The recorded videotape showed a clear image of RBC
      without tailing because of flash (strobe light) illumination, and this allowed
      accurate analysis of the RBC flow rate and capillary hematocrit. During
      hemodilution up to a 50% level of blood exchange, the functional capillary
      density remained unchanged and it started to decline significantly at the 60%
      level of blood exchange and reached 37 +/- 32% of the basal value at the 80%
      level of blood exchange. The RBC flow rates monotonously increased up to 294 +/-
      110% of the basal value at the 60% level of blood exchange, which was in contrast
      to the abdominal aortic blood flow increase to 148 +/- 20%. Capillary hematocrit
      did not appear to fall in the same proportion as the systemic hematocrit, which
      coincided with the previous observations. These results indicate that
      microhemodynamic properties during hemodilution can be transcutaneously analyzed
      with this new technique without surgical preparation of the skin.

PMID- 12074639
TI  - Chronic hydralazine improves flow (shear stress)-induced endothelium-dependent
      dilation in mouse mesenteric resistance arteries in vitro.
AB  - Flow (shear stress)-mediated dilation (FMD) plays a key role in the local control
      of vascular diameter and blood flow supply. Although vasodilator treatments
      improve FMD in diverse models of hypertension, FMD may also change in situations
      where systemic blood pressure is not affected. In pathological situations such as
      ischemia, local blood flow and vascular density are increased by vasodilators not
      affecting systemic blood pressure. As the mechanisms involved remain obscure, we
      studied FMD in resistance arteries from mice treated chronically (1 month) with
      hydralazine (200 mg/L in drinking water). Blood flow in mesenteric arteries of
      mice treated with hydralazine was significantly increased (130 +/- 15 to 169 +/-
      27 microl/min, n = 10/group), whereas mean arterial blood pressure was not
      affected (79 +/- 5 vs 82 +/- 3 mm Hg in controls). Mesenteric resistance arteries
      (90 microm internal diameter, 75 mm Hg) were isolated and mounted in vitro in an
      arteriograph. Pressure (myogenic tone)-, phenylephrine-, and KCl-induced
      contractions, as well as acetylcholine- and sodium nitroprusside-induced
      dilations, were unaffected by hydralazine. Flow-mediated dilation in arteries
      from hydralazine-treated mice was significantly increased, especially for low
      flow values (up to sevenfold). L-NAME-sensitive and indomethacin-sensitive FMD
      were both increased by hydralazine. Passive arterial diameter increased and
      arterial wall thickness decreased after chronic hydralazine. This is the first
      functional evidence that flow (shear stress)-mediated dilation in resistance
      arteries is improved by a chronic treatment with a nonselective vasodilator. This
      arteriolar adaptation to a chronic increase in blood flow might be of importance
      in the pathophysiology of ischemic diseases.

PMID- 12074641
TI  - The embryonic angiogenic factor Del1 accelerates tumor growth by enhancing
      vascular formation.
AB  - Del1 is a unique alpha v beta 3 integrin ligand that is produced by endothelial
      cells, and thus provides an autocrine signaling pathway in this cell type. It is
      expressed transiently in the embryo and mediates cell attachment, migration, and
      activation of cytoplasmic signaling molecules in focal contacts. Del1 also
      activates angiogenesis in the chick chorioallantoic membrane assay. Reexpression
      of this embryonic signaling molecule has now been documented in naturally
      occurring human tumors, where it is expressed by both tumor cells and angiogenic
      endothelial cells, suggesting that Del1 is important in mediating angiogenesis
      under pathophysiological conditions in the adult. To investigate the role of Del1
      in tumor growth and angiogenesis, human 143B osteosarcoma cells and murine Lewis
      lung carcinoma cells were engineered to express Del1 and compared to control
      transfectants for their ability to produce tumors in nude or syngeneic mice,
      respectively. Del1 expressing tumors showed a two- to fourfold increase in
      capillary density and an accelerated rate of growth. Expression of Del1 also
      correlated with a decrease in apoptosis in tumor cells in vivo. Taken together,
      these data suggest that Del1 acts as an angiogenic factor in the context of solid
      tumor formation and that this increase in vascularization accelerates tumor
      growth through decreased apoptosis.

PMID- 12074640
TI  - Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on
      endothelial cells.
AB  - The main objective of this study was to identify molecular mechanisms through
      which angiopoietin-1 (Ang-1), a ligand for Tie-2 receptors, influences
      endothelial cell apoptosis. Human umbilical vein endothelial cells were cultured
      in a medium enriched with 2% fetal bovine serum (FBS) and growth supplements.
      Apoptosis was induced over 24 h by reducing FBS to 0.1%. Activation of caspase-9,
      -8, -7, and -3 and the expression of Bcl-2 family proteins, inhibitors of
      apoptosis (IAPs), cytochrome c, as well as Smac proteins were evaluated with
      immunoblotting. Ang-1 clearly attenuated serum deprivation-evoked apoptosis, an
      effect which required Tie-2 receptor activation. Activation of caspase-9, -7, and
      -3, but not caspase-8, was inhibited by Ang-1. The inhibitory effects of Ang-1 on
      apoptosis and caspase activation were reversed by a PI-3 kinase inhibitor
      (wortmannin). Ang-1 exposure upregulated the expression of Survivin but not XIAP
      (members of IAPs), reduced the cystosolic levels of Smac, but not that of
      cytochrome c, and had no effect on the expression of Bcl-2 family proteins. This
      is the first study to report on the mitochondrial mechanisms through which Ang-1
      inhibits apoptosis and to investigate the role of the newly discovered Smac. We
      conclude that Ang-1 inhibits endothelial cell apoptosis through several pathways,
      which include PI-3 kinase/AKT activation, inhibition of Smac release from the
      mitochondria, and upregulation of Survivin protein.

PMID- 12074642
TI  - Vascular endothelial growth factor family and receptor expression in human
      choroidal neovascular membranes.

PMID- 12074643
TI  - Thermal therapy of prostate tumor tissue in the dorsal skin flap chamber.

PMID- 12074644
TI  - Prevascularization of a biomaterial using a chorioallontoic membrane.

PMID- 12074645
TI  - Endothelin-a receptor in rat skeletal muscle microvasculature.
AB  - Although the effect of endothelin-1 (ET-1) on vascular tone has been studied
      extensively at the arterial/arteriolar level, little is known about the direct
      effect of ET-1 at the level of the capillary. Using intravital microscopy, we
      determined capillary red blood cell velocity and arteriolar diameter responses to
      ET-1, ET(A)-receptor blocker BQ-123, and ET(B)-receptor blocker BQ-788 applied
      locally on capillaries in rat extensor digitorum longus (EDL) muscle. Using
      immunohistochemistry, we examined capillaries in this muscle and microvascular
      endothelial cells isolated from this muscle for immunoreactivity with ET(A)
      receptor antibody. ET-1 (10(-9) to 10(-5) M in micropipette) caused quick
      reductions (i.e., within several seconds), whereas BQ-123 (10(-8) to 10(-4) M)
      and BQ-788 (10(-6) and 10(-4) M) caused quick increases, in both velocity and
      diameter. Capillaries and endothelial cells showed ET(A)-receptor
      immunoreactivity. We conclude that the microvasculature of the rat EDL muscle is
      sensitive to ET-1 and its receptor blockers and that the ET(A) receptor may be
      present in the capillary wall of this muscle, including the endothelium.

PMID- 12074646
TI  - Platinum oxide (PtO(2)): a potent hydrosilylation catalyst.
AB  - [reaction: see text] Platinum oxide was found to be a versatile and powerful
      hydrosilylation catalyst upon a wide variety of functionalized alkenes and
      especially aminated alkenes. Moreover, highly reproducible results and easy
      removal make this new catalyst a useful tool for hydrosilylation reaction.

PMID- 12074647
TI  - Inversion of the direction of stereoinduction in the coupling of chiral
      gamma,delta-unsaturated Fischer carbene complexes with o-ethynylbenzaldehyde.
AB  - [reaction: see text] A variety of gamma,delta-unsaturated carbene complexes that
      feature a stereogenic center at the beta-carbon couple with 2-ethynylbenzaldehyde
      to afford hydrophenanthrene derivatives with a high degree of stereoinduction.
      The direction of stereoinduction is opposite for examples where the stereogenic
      center is acyclic vs examples where it is within a ring.

PMID- 12074648
TI  - Total synthesis of pyridovericin: studies toward the biomimetic synthesis of
      pyridomacrolidin.
AB  - [reaction: see text] The total synthesis of the novel metabolite pyridovericin 1
      is reported. The synthesis of this key intermediate in our proposed biomimetic
      synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily
      available 2,4-dihydroxypyridine.

PMID- 12074649
TI  - The first versatile synthetic approach to cofacial bis-porphyrins with calixarene
      spacers.
AB  - [structure: see text] A versatile stepwise synthetic approach to cofacial bis
      porphyrin species with calix[4]arene spacers has been designed. The three
      examples described demonstrate that the method allows selection, in a tailor-made
      fashion, of the calix[4]arene conformation, the type of functionalization of the
      calixarene rims, and the anchoring point of the chromophores on the calix[4]arene
      spacer.

PMID- 12074650
TI  - An amino alcohol ligand for highly enantioselective addition of organozinc
      reagents to aldehydes: serendipity rules.
AB  - [reaction: see text] Amino alcohol 4 (or its enantiomer) is prepared in two
      simple steps. Commercial (1R,2S)-2-amino-1,2-diphenylethanol is dialkylated with
      bis(2-bromoethyl) ether. Subsequent hydrogenation over 5% Rh on alumina in the
      presence of morpholine unexpectedly stops at the hexahydro derivative 4. Amino
      alcohol 4 promotes the enantioselective addition of diethylzinc to aldehydes at
      room temperature in up to 99% enantiomeric excess.

PMID- 12074651
TI  - Stereochemical aspects of the iodine(III)-mediated aziridination reaction of some
      cyclic allylic carbamates.
AB  - [reaction: see text] The iodine(III)-mediated aziridination reaction of an
      indolyl-substituted carbamate requires a Rh(II) catalyst and proceeds by a
      metallonitrene intermediate. Stepwise addition across the indole pi-bond followed
      by Rh(II) detachment generates a metal-free zwitterion, which ultimately leads to
      the observed products. In contrast, intramolecular aziridination of several
      cycloalkenyl carbamates does not require a Rh(II) catalyst and occurs via an
      iminoiodinane intermediate.

PMID- 12074653
TI  - Lewis acid-catalyzed ring-opening reactions of methylenecyclopropanes with
      alcoholic or acidic nucleophiles.
AB  - [reaction: see text] Methylenecyclopropanes can react with various nucleophiles
      such as alcohols, phenols, carboxylic acids, and thiols to give the corresponding
      homoallylic esters or ethers in good yields with good stereoselectivities in the
      presence of Lewis acids.

PMID- 12074654
TI  - Chiral hybrid metal-organic dendrimers.
AB  - [structure: see text] New chiral terpyridines containing Frechet-type dendrons
      have been readily synthesized by coupling dendritic benzyl bromide and 4'-[6
      (2,2'-dihydroxy-1,1'-binaphthyl)]-2,2':6'2' '-terpyridine. These chiral dendritic
      terpyridines were used to efficiently construct high molecular weight hybrid
      metal-organic dendrimers based on the Ru(II)-bis(terpy) linkage. Preliminary
      fluorescence measurements show generation-dependent fluorescence quenching
      behavior of 3,5-dimethoxybenzyl peripherals by the [Ru(terpy)(2)](2+) unit.

PMID- 12074652
TI  - Facile cleavage of triethylsilyl (TES) ethers using o-iodoxybenzoic acid (IBX)
      without affecting tert-butyldimethylsilyl (TBS) ethers.
AB  - [reaction: see text] In DMSO cleavage of triethylsilyl (TES) ethers by o
      iodoxybenzoic acid (IBX) was significantly faster than cleavage of tert
      butyldimethylsilyl (TBS) ethers or further oxidation into carbonyl compounds. In
      most cases, TES protecting groups could be removed in good to excellent yields
      within 1 h, whereas similar TBS protecting groups remained intact under the same
      conditions. The procedure also could be adapted for direct one-pot conversion of
      TES ethers into carbonyl compounds.

PMID- 12074656
TI  - Synthesis and characterization of highly fluorescent indenofluorenes.
AB  - [structure: see text] Described here are the synthesis and optical and
      electrochemical properties of a series of indenofluorenes as new building blocks
      for electronic and optoelectronic materials.

PMID- 12074655
TI  - Asymmetric alkyldifluoroboranes and their use in secondary amine synthesis.
AB  - [reaction: see text] Asymmetric diol boronic esters with potassium bifluoride
      form the corresponding alkyltrifluoroborate and free diol under mild conditions.
      Defluoridation with tetrachlorosilane produces an alkyldifluoroborane
      intermediate. This conversion of relatively unreactive boronic esters to
      derivatives that are strong Lewis acids opens new synthetic opportunities, as
      illustrated by the preparation of (R)-2-phenylpyrrolidine in 98% ee from a
      pinanediol or 1,2-dicyclohexyl-1,2-ethanediol boronic ester via potassium (2
      phenyl-4-azidobutyl)trifluoroborate.

PMID- 12074657
TI  - The first synthetic receptor for the RGD sequence.
AB  - [structure: see text] The combination of an optimized arginine receptor unit with
      a semirigid linker carrying a strategically placed primary ammonium group leads
      to the first synthetic RGD receptor. It binds to the free RGD peptide as well as
      to cyclo(RGDfV) in water with association constants around 1000 M(-1). RGD
      mimetics such as benzamidine 6 are not recognized, rendering the new host a
      prototype of a new class of receptors selective for the true RGD sequence in
      peptides.

PMID- 12074658
TI  - Porphyrin-containing molecular capsules: metal mediated dimerization of a bis
      porphyrin cavity.
AB  - [reaction] A self-complementary V-shaped bis-porphyrin cavity has been
      synthesized that is capable of dimerization to form a capsule structure. Self
      assembly of the dimer occurs via metal ion coordination and produces an internal
      volume for guest encapsulation.

PMID- 12074660
TI  - Synthesis of cyclic (alpha(2)beta)-tripeptides as potential peptide turn
      mimetics.
AB  - [reaction: see text] The solid-supported synthesis followed by cyclization in
      solution of cyclic (alpha(2)beta)-tripeptides, potential peptide beta-turn
      mimetics, is described. The cyclization takes advantage of facilitating the
      rotation between trans- and cis-rotamers of two amide bonds. The method is
      amenable to combinatorial approaches as is illustrated by the synthesis of a
      small array of cyclic (alpha(2)beta)-tripeptides.

PMID- 12074659
TI  - Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1
      decynyl)-benzolactam-V8 as protein kinase C modulators.
AB  - [structures: see text] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1
      decynyl)benzolactam-V8 were designed and synthesized as PKC modulators.
      Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)
      counterpart in binding to PKC alpha.

PMID- 12074661
TI  - Synthesis of the ABC ring system of azaspiracid. 1. Effect of D ring truncation
      on bis-spirocyclization.
AB  - [reaction: see text] Synthesis of a spirocyclization precursor with a truncated D
      ring has been accomplished. Subsequent bis-spirocyclization induced the formation
      of equal amounts of the natural transoidal 10R,13R bis-spirocycle and its
      cisoidal 10R,13S epimer under an apparent thermodynamically controlled process.

PMID- 12074663
TI  - Hydrogen-bonded charge-transfer complexes of TTF containing a uracil moiety:
      crystal structures and electronic properties of the hydrogen cyananilate and TCNQ
      complexes.
AB  - [structure: see text] A novel TTF-based donor with a uracil moiety, TTF-(1-n
      butyluracil-5-yl) (TnbU), was synthesized. Crystal structures of both TnbU and
      the charge-transfer complex of TnbU-hydrogen cyananilate possess complementary
      double hydrogen bonds through uracil moieties and pi-stacking dimer structures
      between TTF skeletons. Furthermore, the TnbU-TCNQ charge-transfer complex shows a
      high electrical conductivity underlying the partial charge-transfer accompanied
      by a hydrogen-bonding interaction, which was substantiated in terms of the
      measurements of the IR, electronic spectra, and conductivity.

PMID- 12074662
TI  - Synthesis of the ABC ring system of Azaspiracid. 2. A systematic study into the
      effect of C(16) and C(17) substitution on bis-spirocyclization.
AB  - [reaction: see text] A systematic study into the effect of C(16) and C(17)
      substitution on the stereochemical outcome of bis-spirocyclization to form the
      ABC ring system of azaspiracid is disclosed. Successful construction of the
      natural 10R,13R bis-spirocyclic stereochemistry has been accomplished on the
      C(16) benzyloxy-containing precursor.

PMID- 12074664
TI  - Asymmetric synthesis of 2-alkenyl-1-cyclopentanols via tin-lithium exchange and
      intramolecular cycloalkylation.
AB  - [reaction: see text] We report a method for the synthesis of chiral cyclopentanes
      using tin-lithium exchange and cycloalkylation reactions. The sec-butyllithium/(
      )-sparteine-mediated deprotonation of an alkyl carbamate and subsequent
      substitution furnishes a highly enantioenriched stannane as a stable carbanion
      equivalent. It was transformed into suitable cyclization precursors, which
      underwent tin-lithium exchange and stereoselective cycloalkylation when reacted
      with n-butyllithium, giving highly enantioenriched cyclopentanes in very good
      yields. A kinetic resolution was observed with a higher substituted stannane.

PMID- 12074665
TI  - Synthesis of an ethynyl carbamate and application for enantioselective
      cyclocarbolithiation.
AB  - [reaction: see text] The intramolecular trans-cyclocarbolithiation of the alpha
      lithiated 4-substituted 5-hexynyl carbamate (1S,4RS)-14 employing
      lithiodestannylation is presented. The 5-exo-dig cyclization products cis-/trans
      16a were formed exclusively. The highly enantioenriched organotin precursor (S)
      11 was synthesized via an asymmetric deprotonation of the corresponding alkyl
      carbamate 10 by the chiral complex sec-butyllithium/(-)-sparteine and subsequent
      substitution with tributyltin chloride.

PMID- 12074666
TI  - OsO(4) in ionic liquid [Bmim]PF(6): a recyclable and reusable catalyst system for
      olefin dihydroxylation. remarkable effect of DMAP.
AB  - [reaction: see text] The combination of the ionic liquid [bmim]PF(6) and DMAP
      provides a most simple and practical approach to the immobilization of OsO(4) as
      catalyst for olefin dihydroxylation. Both the catalyst and the ionic liquid can
      be repeatedly recycled and reused in the dihydroxylation of a variety of olefins
      with only a very slight drop in catalyst activity.

PMID- 12074667
TI  - A concise synthesis of all four possible benzo[4,5]furopyridines via palladium
      mediated reactions.
AB  - [reaction: see text] By taking advantage of the alpha- and gamma-activation of
      chloropyridines as well as palladium-mediated reactions, all four possible
      benzo[4,5]furopyridine tricyclic heterocycles, benzo[4,5]furo[2,3-b]pyridine,
      benzo[4,5]furo[2,3-c]pyridine, benzo[4,5]furo[3,2-c]pyridine, and
      benzo[4,5]furo[3,2-b]pyridine, are efficiently synthesized from 2-chloro-3
      iodopyridine, 3-chloro-4-stannylpyridine, 4-chloro-3-iodopyridine, and 2-chloro-3
      hydroxypyridine, respectively.

PMID- 12074668
TI  - Synthesis of the core structure of salicylihalamide A by intramolecular Suzuki
      reaction.
AB  - [reaction: see text] An intramolecular Suzuki coupling was used to establish the
      core structure of the benzolactone enamide salicylihalamide A. This strategy
      combines a diastereoselective hydroboration with a subsequent cross-coupling.

PMID- 12074669
TI  - One-step ethynylation of silyl enol ether with chlorosilylethyne.
AB  - [reaction: see text] In the presence of GaCl(3), silyl enol ethers are
      ethynylated at the alpha-carbon atom with chlorotrimethylsilylethyne. This
      reaction can provide alpha-ethynylated aryl ketones possessing acidic alpha
      protons without isomerization to conjugated allenyl ketones.

PMID- 12074670
TI  - Electron-donating properties of p-phenylene phosphine imides: an electrochemical
      and spectroscopic investigation.
AB  - [reaction: see text] Electronic properties of phosphine imide based organic
      electron donors have been investigated. N,N'-p-Phenylenebis(triphenyl)phosphine
      imide (Ph(3)P=NC(6)H(4)N=PPh(3), 1) has two reversible single-electron oxidations
      (0.04 and 0.53 V vs SCE). Spectroscopic investigations of poly(p-phenylene
      phosphine imide)s (2) are similar to those of polymer model compounds, suggesting
      formation of localized radical cations on the polymer chains and electronically
      insulating phosphorus atoms.

PMID- 12074671
TI  - Stereoselective synthesis of cycloheptanone derivatives via an intermolecular [5
      + 2] cycloaddition reaction.
AB  - [reaction: see text] A [5 + 2] cycloaddition reaction of a new five-carbon unit
      was developed on the basis of a dicobalt hexacarbonyl propargyl cation species.
      Under the influence of EtAlCl(2), [5-benzoyloxy-2-(triisopropylsiloxy)-1-penten-3
      yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield
      seven-membered dicobalt acetylene complexes in good yield. The reactions with
      cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited
      remarkably high diastereoselectivity. The cycloadducts can be easily converted
      into various kinds of cycloheptanone derivatives.

PMID- 12074672
TI  - Synthetic studies toward SNF4435 C and SNF4435 D.
AB  - [reaction: see text] A synthetic approach toward the immunosuppressants SNF3345 C
      and SNF4435 D featuring a tandem Stille coupling/electrocyclization cascade is
      described.

PMID- 12074673
TI  - Diastereo- and enantioselective carbolithiation of allyl o-lithioaryl ethers. New
      chiral cyclopropane derivatives.
AB  - [reaction: see text] Different allyl 2-lithioaryl ethers undergo a tandem
      carbolithiation/gamma-elimination in Et(2)O/TMEDA affording o-cyclopropyl phenol
      or naphthol derivatives in a diastereoselective manner. The use of (-)-sparteine
      as a chiral ligand instead of TMEDA allows the synthesis of cyclopropane
      derivatives with up 81% ee.

PMID- 12074674
TI  - An air-stable palladium/N-heterocyclic carbene complex and its reactivity in aryl
      amination.
AB  - [reaction: see text] The synthesis and characterization of [Pd(IPr)Cl(2)](2) (1),
      an air- and moisture-stable complex, is reported. The utilization of 1 as a
      catalyst for amination of aryl chlorides and bromides with a variety of amine
      coupling partners under mild conditions is described. The amination reactions
      with 1 show a remarkable insensitivity to oxygen and water, and thus the
      amination reactions could be performed in air on the benchtop with undried
      reagent grade solvents and substrates with small effects on reaction times and
      conversions.

PMID- 12074675
TI  - Simultaneous preparation of four truncated analogues of discodermolide by
      fluorous mixture synthesis.
AB  - [structure: see text] Four truncated analogues of the natural product
      discodermolide were synthesized in a single synthetic sequence. Precursors
      bearing four different groups at C22, each with a unique fluorous p-methoxybenzyl
      substituent on the C17 hydroxy group, were mixed and taken through an nine-step
      sequence. Demixing by fluorous chromatography followed by deprotection and
      purification provided the individual analogues in 3-7% overall yields and with a
      savings of 24 synthetic steps. Fluorous mixture synthesis is recommended as a new
      technique to make multiple natural product analogues in a single multistep
      synthesis.

PMID- 12074676
TI  - Total synthesis of (+/-)-O-methyl PD 116740.
AB  - [reaction: see text] Condensation of the phthalide sulfide with an ortho-quinone
      monoketal was employed as a key step in the first total synthesis of a derivative
      of (+/-)-PD 116740.

PMID- 12074677
TI  - Regiospecific synthesis of a benanomicinone/pradimicinone analogue.
AB  - [reaction: see text] Condensation of a phenylsulfinyl naphthoate with an ortho
      quinone monoketal has been used to accomplish a total synthesis of a
      benanomicinone/pradimicinone analogue.

PMID- 12074678
TI  - Convenient divergent synthesis of a library of trehalosamine analogues.
AB  - [reaction: see text] A library of seven trehalosamine analogues with various
      natural and non-natural binding motifs was synthesized through an expedient
      divergent synthetic approach. The final products were prepared in sufficient
      quantities and purities for different types of assay against various pathogens.
      Several stereo- and regioselective reactions on the trehalose scaffold were
      developed for rapid synthesis of all of the designed compounds.

PMID- 12074679
TI  - Novel [6 + 2] cycloaddition of fulvenes with alkenes: a facile synthesis of the
      anislactone and hirsutane framework.
AB  - [reaction: see text] In contrast to the Diels-Alder reaction of fulvenes and
      various alkenes, 6-aminofulvenes react with maleic anhydride (or maleimide) to
      give [6 + 2] cycloaddition adducts, constituting an efficient and novel route to
      pentaleno[1,2-c]furan, pentaleno[1,2-c]pyrrole, and cyclopenta[a]pentalene
      skeleton.

PMID- 12074680
TI  - Practical and highly selective oxazolidinethione-based asymmetric acetate aldol
      reactions with aliphatic aldehydes.
AB  - [reaction: see text] The utility of a valine-derived oxazolidinethione for
      auxiliary-based asymmetric acetate aldol reactions is reported. Titanium(IV)
      chloride, along with (-)-sparteine and N-methylpyrrolidinone, is employed for
      enolization. Subsequent aldol reaction with aliphatic aldehydes occurs with high
      diastereoselectivity (from 92:8 to 99:1 dr).

PMID- 12074681
TI  - Cobalt-catalyzed intramolecular Heck-type reaction of 6-halo-1-hexene
      derivatives.
AB  - [reaction: see text] Treatment of 6-iodo-1-hexene derivatives with
      trimethylsilylmethyl Grignard reagent in the presence of CoCl(2)(dppb) in
      refluxing THF affords Heck-type products, methylenecyclopentanes, in good yields.

PMID- 12074682
TI  - Generation, direct observation, and kinetics of triplet 9-(1,1,4,4,5,5,8,8
      octamethyl-1,2,3,4,5,6,7,8-octahydro- anthryl)phenylcarbene.
AB  - [structure: see text] Reactivities of the title triplet carbene were compared
      with those of the "untied" counterpart, [2,4,6
      tris(tert)butylphenyl](phenyl)carbene. An appreciable increase in the stability
      of triplet carbene is noted by tuning the distance between the o-hydrogen and the
      carbene center.

PMID- 12074683
TI  - Synthesis and use of alpha-silyl-substituted alpha-hydroxyacetic acids.
AB  - [reaction: see text] Rhodium-catalyzed oxygen transfer was used to generate
      benzyl 2-silyl-2-oxoacetates in good yields. The hydrogenation of these compounds
      led to chiral alpha-silyl-substituted alpha-hydroxyacetic acids. Resolution by
      means of HPLC using a chiral stationary phase afforded an enantiomerically pure
      representative of this class of compounds, which was successfully applied as a
      chiral ligand in an asymmetric aldol-type reaction.

PMID- 12074684
TI  - Stereoselective synthesis of polysubstituted 2,5-dihydrofurans from reaction of
      1,4-dilithio-1,3-dienes with aldehydes.
AB  - [reaction: see text] Reaction of 1,4-dilithio-1,3-diene derivatives with 2 equiv
      of aldehydes affords polysubstituted 2,5-dihydrofurans in good to high yields
      with perfect regio- and stereoselectivities. Hexa-2,4-diene-1,6-dialcoholates are
      proposed as the first intermediates, which undergo a cyclization and subsequent
      elimination of Li(2)O to generate the 2,5-dihydrofuran derivatives.

PMID- 12074685
TI  - Synthesis and structure of preorganized, C(3)-symmetric trilactam scaffolds with
      convergently oriented (S)-acetylthiomethyl appendages.
AB  - [reaction: see text] Efficient modular synthesis of conformationally
      preorganized, C(3)-symmetric trilactams is reported. The allyl acetate
      cyclization substrate was synthesized in five steps from Garner's L-serine
      derived aldehyde. After chiral ligand-mediated palladium cyclization, the
      resulting vinyl hydropyran was transformed into the orthogonally protected amino
      acids for iterative coupling. The final macrolactamization was accomplished using
      EDCI/HOBt or HATU/HOAt under high dilution conditions.

PMID- 12074686
TI  - Cobalt cluster-containing carbonyl ylides for catalytic, three-component assembly
      of oxygen heterocycles.
AB  - [reaction: see text] A dicobalt hexacarbonyl (Co(2)(CO)(6)) cluster is essential
      for the unusually broad dipolarophile scope and for the sense and degree of
      diastereoselection in a catalytic, three-component synthesis of tetrahydrofurans
      and dihydrofurans. Likely involving a new class of carbonyl ylide, these
      cycloadditions are stereospecific with respect to the dipolarophile and exhibit
      high diastereoselectivity and regioselectivity in most cases. Differentiation of
      all four positions of the tetrahydrofuran can thus be accomplished in a triply
      convergent manner.

PMID- 12074687
TI  - Synthesis of L-sugars from 4-deoxypentenosides.
AB  - [reaction: see text] 4-Deoxypentenosides, which are readily derived from D
      sugars, resemble glycals in structure and reactivity and can undergo
      stereoselective epoxidation and S(N)2 nucleophilic addition to produce L-sugars
      in pyranosidic form.

PMID- 12074688
TI  - Kinetic and dynamic models of diving gases in decompression sickness prevention.
AB  - Decompression sickness is a complex phenomenon involving gas exchange, bubble
      dynamics and tissue response. Relatively simple deterministic compartmental
      models using empirically derived parameters have been the mainstay of the
      practice for preventing decompression sickness since the early 1900s. Decades of
      research have improved our understanding of decompression physiology, and the
      insights incorporated in decompression models have allowed people to dive deeper
      into the ocean. However, these efforts have not yet, and are unlikely in the near
      future, to result in a 'universal' deterministic model that can predict when
      decompression sickness will occur. Divers using current recreational dive
      computers need to be aware of their limitations. Probabilistic models based on
      the estimation of parameters using modern statistical methods from large
      databases of dives offer a new approach and can provide a means of
      standardisation of deterministic models. Future improvements in decompression
      practice will depend on continued improvement in understanding the kinetics and
      dynamics of gas exchange, bubble evolution and tissue response, and the
      incorporation of this knowledge in risk models whose parameters can be estimated
      from large databases of human and animal data.

PMID- 12074690
TI  - Clinical pharmacokinetics of leflunomide.
AB  - Leflunomide is the first disease-modifying antirheumatic drug to be approved for
      rheumatoid arthritis in the past 10 years. Orally administered leflunomide is
      almost completely converted into its active metabolite A77 1726 (hereafter
      referred to as M1). M1 displays linear pharmacokinetics at the dosages of
      leflunomide used in clinical practice. It has a long elimination half-life
      (approximately 2 weeks), reaching a steady state after approximately 20 weeks. M1
      is highly bound to plasma proteins. The pharmacokinetics of M1 are not affected
      by food intake, and dosage requirements are not influenced by age or gender.
      Approximately 90% of a single dose of leflunomide is eliminated, 43% in urine,
      primarily as leflunomide glucuronides and an oxalinic acid derivative of M1, and
      48% in faeces, primarily as M1. Elimination can be dramatically increased by
      using charcoal or cholestyramine. In vitro studies have shown no major influence
      of leflunomide on the metabolism of analgesics, nonsteroidal anti-inflammatory
      drugs and methotrexate, drugs usually used in the treatment of rheumatoid
      arthritis. In clinical studies with a limited number of patients using these
      drugs concomitantly, no safety problems appeared. Nonspecific inducers of
      cytochrome P450 (CYP) and some drugs metabolised by CYP2C9 affect the metabolism
      of M1, and caution should be used in patients cotreated with them. Additional in
      vitro and in vivo pharmacokinetic studies are needed to better understand the
      nonenzymatic and enzymatic metabolism of leflunomide. Additional clinical trials
      should be performed in order to find new indications for leflunomide in other
      autoimmune diseases, and new combination therapeutic strategies in rheumatoid
      arthritis. This review is a summary of current knowledge of the pharmacokinetics
      of leflunomide, focusing primarily on humans and in particular on patients with
      rheumatoid arthritis.

PMID- 12074689
TI  - Pharmacokinetics of the carmustine implant.
AB  - Controlled release delivery of carmustine from biodegradable polymer wafers was
      approved as an adjunct to surgical resection in the treatment of recurrent
      glioblastoma multiforme after it was shown in clinical trials to be well
      tolerated and effective. Given the localised nature of the drug in the brain
      tissue, no direct pharmacokinetic measurements have been made in humans after
      implantation of a carmustine wafer. However, drug distribution and clearance have
      been extensively studied in both rodent and non-human primate brains at various
      times after implantation. In addition, studies to characterise the degradation of
      the polymer matrix, the release kinetics of carmustine and the metabolic fate of
      the drug and polymer degradation products have been conducted both in vitro and
      in vivo. GLIADEL wafers have been shown to release carmustine in vivo over a
      period of approximately 5 days; when in continuous contact with interstitial
      fluid, wafers should degrade completely over a period of 6 to 8 weeks. Metabolic
      elimination studies of the polymer degradation products have demonstrated that
      sebacic acid monomers are excreted from the body in the form of expired CO(2),
      whereas 1,3-bis-(p-carboxyphenoxy)propane monomers are excreted primarily through
      the urine. Carmustine degradation products are also excreted primarily through
      the urine. Pharmacokinetic studies in animals and associated modelling have
      demonstrated the capability of this modality to produce high dose-delivery
      (millimolar concentrations) within millimetres of the polymer implant, with a
      limited penetration distance of carmustine from the site of delivery. The limited
      spread of drug is presumably due to the high transcapillary permeability of this
      lipophilic molecule. However, the presence of significant convective flows due to
      postsurgical oedema may augment the diffusive transport of drug in the hours
      immediately after wafer implantation, leading to a larger short-term spread of
      drug. Additionally, in non-human primates, the presence of significant doses in
      more distant regions of the brain (centimetres away from the implant) has been
      shown to persist over the course of a week. The drug in this region was presumed
      to be transported from the implant site by either cerebral blood flow or
      cerebrospinal fluid flow, suggesting that although drug is able to penetrate the
      blood-brain barrier at the site of delivery, it may re-enter within the confines
      of the brain tissue.

PMID- 12074691
TI  - Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer
      drugs.
AB  - The anthracycline glycoside antibiotics represent a group of potent anticancer
      agents with a wide spectrum of activity against solid tumours and haematological
      malignancies, and are the mainstay of a large number of clinical protocols for
      the treatment of adult and childhood neoplastic diseases. Their clinical activity
      is limited, however, by acute and chronic adverse effects. Myelosuppression,
      predominantly neutropenia and leucopenia, is the dose-limiting toxicity; in
      addition to this, mucositis, nausea, vomiting and alopecia are frequent, whereas
      hepatopathy, characterised by elevated bilirubin concentrations, occurs less
      frequently. Cardiotoxicity is a major adverse effect of the anthracycline
      antibiotics and can be acute or chronic; in the acute setting,
      electrocardiographic abnormalities may be seen, including ST-T elevations and
      arrhythmias, but chronic cardiotoxicity represents a serious adverse effect that
      may be lethal due to the development of irreversible, cumulative dose-dependent,
      congestive cardiomyopathy. The occurrence of toxicity displays a marked
      interindividual variation, and for this reason the pharmacokinetics and
      pharmacodynamics of anthracyclines have been extensively investigated in order to
      identify integrated models that can be used in the clinical setting to prevent
      the development of serious toxicity, mainly leucopenia, and maximise tumour
      exposure. Pharmacokinetics has been recognised to influence both the toxicity and
      the activity of anthracyclines; in particular, there is increasing evidence that
      the mode of administration plays an important role for cumulative cardiotoxicity
      and data indicate that bolus administration, rather than continuous infusion,
      appears to be an important risk factor for anthracycline-induced cardiomyopathy,
      thus implying that this type of toxicity is maximum concentration-dependent. On
      the contrary, exposure to the drug, as measured by area under the curve, seems
      best related to the occurrence of leucopenia. Finally, the development of
      pharmacokinetic-pharmacodynamic models allows the simulation of drug effects and
      ultimately dose optimisation in order to anticipate important toxicities and
      prevent their occurrence by the administration of prophylactic treatments.

PMID- 12074693
TI  - Application of a colorimetric chain-termination assay for characterization of
      reverse transcriptase from 3'-azido-2',3'-deoxythymidine-resistant HIV isolates.
AB  - Two different enzyme assays, both based on the interaction of native reverse
      transcriptase (RT) and 3'-azido-2',3'-deoxythymidine triphosphate (AZT-TP), were
      used to characterize the enzymes from 18 HIV-1 isolates with decreased
      sensitivity to AZT in cell culture. The first assay, which measures the balance
      between incorporation and excision of AZT monophosphate in the presence of dNTP
      substrate (in terms of IC(50)), gave an approx. 9-fold variation in sensitivity
      to AZT-TP. There was a correlation between the IC(50) values and the sensitivity
      of the corresponding virus to AZT in cell culture (r=0.60, P<0.01). The second
      assay, which was designed specifically for measurement of chain termination in
      the absence of dNTP substrate (as the concentration of AZT-TP giving 50% residual
      primer function, or CT(50)), revealed a more than 600-fold difference between the
      different isolate RTs. For the majority of enzymes there was a strict correlation
      between the results from the two assays; however, four isolates exhibited
      significantly higher CT(50)/IC(50) ratios than the other isolates. These
      differences were not related to sensitivity of the corresponding viruses to AZT
      but to the occurrence of certain mutations in their pol gene. The four deviating
      isolates contained either a minimum of four AZT-specific substitutions, including
      Thr-215-->Tyr (isolates 134 and 143), or some of the known specific substitutions
      combined with Thr-39-->Ala (isolates 80 and 157). The Thr-39-->Ala substitution
      has previously been recorded in connection with AZT/Foscarnet combination
      therapy.

PMID- 12074694
TI  - Bioaffinity immobilization of tannase from Aspergillus niger on concanavalin A
      Sepharose CL-4B.
AB  - Tannase from Aspergillus niger van Teighem was immobilized on concanavalin A
      Sepharose via bioaffinity interaction. The immobilized enzyme showed a pH optimum
      similar to that of the free enzyme. K(m) values for free and immobilized enzyme
      were 0.3 and 0.6 mM respectively. V(max) changed from 0.013 to 0.02 micromol x
      min(-1) upon immobilization. The immobilized preparation was quite stable to
      reuse, there was no loss of enzyme activity after three cycles and it retained
      81% activity even after the sixth cycle. Ester hydrolysis using the immobilized
      enzyme led to a 40% conversion into gallic acid as compared with 30% obtained
      with the free enzyme.

PMID- 12074692
TI  - Comparison of pharmacokinetics of lanoteplase and alteplase during acute
      myocardial infarction.
AB  - OBJECTIVE: Lanoteplase is a rationally designed variant of tissue plasminogen
      activator. The aim of this study was to examine the pharmacokinetics and
      functional activity of a single intravenous bolus dose of lanoteplase with those
      of a bolus plus two-step infusion of alteplase. DESIGN: Seven-centre substudy of
      the InTIME-I angiographic trial in patients presenting within 6 hours of onset of
      suspected acute myocardial infarction. PATIENTS AND PARTICIPANTS: A total of 31
      patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26
      to 76) years]. METHODS: Twenty-three patients randomised to lanoteplase received
      single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or
      120 kU/kg (n = 6). Eight patients received alteplase <or=100mg as a bolus
      followed by a two-stage 90 min infusion. Blood samples were analysed for antigen
      concentration and plasminogen activator (PA) activity. RESULTS: The distribution
      plasma half-life of approximately 35 min for lanoteplase was at least five times
      longer than that of alteplase. Lanoteplase plasma clearance averaged 3 L/h (50
      ml/min), whereas the mean plasma clearance of approximately 24 L/h (400 ml/min)
      for alteplase approaches hepatic blood flow following acute myocardial
      infarction. PA activity after lanoteplase 120 kU/kg remained for 6 hours,
      compared with less than 4 hours after alteplase 100mg. CONCLUSIONS: The longer
      antigen and activity half-lives, slower clearance and less complicated
      administration of lanoteplase compared with alteplase suggest that it may offer
      advantages for use as a single intravenous bolus to achieve reperfusion after
      myocardial infarction.

PMID- 12074695
TI  - Effect of medium properties and additives on antibody stability and accumulation
      in suspended plant cell cultures.
AB  - Factors affecting antibody accumulation and stability were investigated in
      transgenic plant cell cultures. Whereas IgG(1) antibody was stably maintained in
      media used for animal cell culture, there was a rapid loss over a period of 1-2 h
      of antibody added to sterile plant culture media. Antibody stability in Gamborg's
      B5 medium was improved in the absence of Mn. Tobacco suspensions producing IgG(1)
      antibody were used to test various medium-based strategies for improving antibody
      accumulation in plant culture. Even though growth was suppressed, antibody levels
      in the biomass and medium were increased in media containing mannitol at
      osmolalities up to approximately 450 mOsm x (kg of water)(-1). Adding gibberellic
      acid and haemin to the cultures was also beneficial, but the effects were not as
      great as those obtained under hyperosmolar conditions. Moderate increases in
      antibody accumulation were found by culturing plant cells in B5 medium without
      Mn.

PMID- 12074696
TI  - Synthesis of cationic polysaccharide derivatives and their hypocholesterolaemic
      capacity.
AB  - High-capacity bile acid-sequestering biopolymers with cationic polysaccharide
      derivatives have been developed. Cholestyramine, the bile acid sequestrant most
      widely used for treating hypercholesterolaemia, has unpleasant side effects
      because of the hydrophobic nature of its backbone. Methylan, a high-viscosity
      polysaccharide produced by Methylobacterium organophilum, was selected as a model
      polysaccharide for derivatization. Methylan was aminated to add dialkylaminoalkyl
      and free amino groups at hydroxyl sites in the methylan backbone, and these
      derivatives were quaternized to produce pH-independent cationic polyelectrolytes.
      The in vitro bile acid-binding capacity of quaternized DEAE-methylan was
      approximately 50% higher than that of cholestyramine. The bile acid-binding
      capacity of methylan derivatives increased with the number of carbons in the
      alkyl groups, indicating that hydrophobic interaction is a secondary factor for
      the sequestration of bile acids.

PMID- 12074697
TI  - Determination of total cholesterol in serum by cholesterol esterase and
      cholesterol oxidase immobilized and co-immobilized on to arylamine glass.
AB  - Commercial cholesterol esterase from bovine pancreas and cholesterol oxidase from
      Brevibacterium recombinant type have been immobilized individually and co
      immobilized on to arylamine glass beads (pore diameter, 55 nm) through
      diazotization. A method for discrete analysis of total cholesterol in serum was
      developed employing individually immobilized cholesterol esterase (0.36 mg/50 mg
      of glass beads) and cholesterol oxidase (0.41 mg/50 mg of glass beads) or co
      immobilized cholesterol esterase and cholesterol oxidase (0.56 mg/100 mg of glass
      beads). Peroxidase from horseradish immobilized on to arylamine glass (0.9 mg/50
      mg of glass beads) was common in both the cases. 4-Aminophenazone (0.25 mg/1.5 ml
      of reaction mixture) and phenol (0.5 mg/1.5 ml of reaction mixture) were used to
      form dye. In the method, cholesterol ester is hydrolysed by cholesterol esterase
      to free fatty acid and cholesterol, which is oxidized by cholesterol oxidase to
      cholestenone and H(2)O(2) x H(2)O(2) is determined enzymically with horseradish
      peroxidase by additive coupling of 4-aminophenazone with phenol, and the
      resulting quinoneimine dye is measured at 520 nm, (epsilon=4.0 x 10(-4)). The
      lower detection limit of the method was 42.8 mg/l for individually immobilized
      enzymes and 21.4 mg/l for co-immobilized enzymes. Within-day and between-day
      coefficients of variation were <1.5% and <4.0% respectively for individually
      immobilized enzymes and <1.0% and <2.5% respectively for co-immobilized enzymes.
      A good correlation (r=0.99) was found between total serum cholesterol obtained by
      the present method and a commercial enzo-kit method employing free enzymes. The
      individually immobilized/co-immobilized enzymes did not show much loss of
      activity after their 300 uses, when stored at 4 degrees C in distilled water. The
      co-immobilized enzymes showed better efficiency in terms of sensitivity,
      linearity and precision compared with individually immobilized enzymes.

PMID- 12074698
TI  - Expression, purification and characterization of a recombinant levan
      fructotransferase.
AB  - A 1.6 kb DNA fragment including the lftM gene, encoding a levan fructotransferase
      (LFTase) of Microbacterium sp. AL-210, was subcloned into a high-expression
      vector, pET-29b, and the recombinant enzyme was overexpressed in Escherichia
      coli. Most of the LFTase activity was detected in the cytoplasmic fraction after
      induction with isopropyl beta-d-thiogalactoside. The recombinant enzyme with a
      tag of six histidine residues at the C-terminus was purified 132-fold by affinity
      and gel-filtration chromatography. Analysis of the N-terminal amino acid sequence
      revealed that the first 42 amino acids were post-translationally cleaved off. The
      molecular mass of the purified LftM was approx. 54 kDa as determined by SDS/PAGE,
      which corresponded well with a predicted size from the nucleotide sequence of the
      lftM gene lacking 42 amino acids. The enzyme converted levan into difructose
      anhydride IV (DFA IV) with a K(m) of 2 mg/ml and a V(max) of 40.6 micromol/min at
      pH 7.0 and 40 degrees C. The pH-dependence study of the enzyme for DFA IV
      production showed that LftM had a broad pH optimum (5.0-8.0) and the pK(a) values
      obtained were 4.5 and 8.9 at 40 degrees C. These results suggest that the acidic
      residues at the active site may play important roles for the catalytic mechanism
      of the LFTase.

PMID- 12074700
TI  - Purification, characterization and cloning of a chitinase from Bacillus sp.
      NCTU2.
AB  - A chitin-degrading Bacillus strain, designated as NCTU2, was screened from soil
      and identified. An extracellular chitinase was purified to >90% homogeneity from
      the culture filtrate. The purification involved hydrophobic-interaction and gel
      filtration chromatographic separations with a yield of 58%. The purified enzyme
      (ChiNCTU2) is a monomeric protein with an estimated molecular mass of 36.5 kDa
      and a pI of 6.3. It is thermally stable at 60 degrees C and pH 6-8 for more than
      3 h. The optimal activity is in the range of 50-60 degrees C at pH 7.0.
      Chitobiose is the predominant product throughout the enzymic hydrolysis of the
      colloidal chitin, indicating that the purified chitinase is an exo-chitinase.
      Chito-oligosaccharides [with degree of polymerization (DP) values of 4-6] are
      good substrates of the purified enzyme, whereas a DP3 oligomer was slowly
      hydrolysed to form DP1 and DP2 sugars. The first 15 N-terminal amino acids of the
      enzyme were determined to be ANNLGSKLLVGYWHN, which is highly homologous to that
      of ChiA from Bacillus cereus. A PCR cloning technique was employed to obtain the
      corresponding gene from Bacillus NCTU2. The gene sequence was determined to be
      1080 bp, encoding a polypeptide of 360 amino acids with the first 27 amino acids
      as the signal peptide.

PMID- 12074699
TI  - Enhancement of the immune response generated against hepatitis C virus envelope
      proteins after DNA vaccination with polyprotein-encoding plasmids.
AB  - Plasmids expressing variants of the hepatitis C virus (HCV) core, E1 and E2
      proteins individually or as polyproteins were administered to BALB/c mice. All
      plasmids induced a detectable and specific antibody response. Antibody titres
      against core, E1 and E2 proteins, 19 weeks after primary immunization, ranged
      from 1:50 to 1:4500 depending on the inoculated plasmid and the HCV antigen
      evaluated. Constructs expressing HCV envelope proteins as polyprotein variants
      including the core amino acid region induced statistically stronger antibody
      responses than plasmids encoding individual E1 and E2 proteins. Particularly, the
      pIDKE2 plasmid, expressing the first 650 amino acids in the viral polyprotein,
      induced a potent and multispecific antibody and lymphoproliferative response
      against HCV core, E1 and E2 proteins. Anti-E2 antibodies generated by pIDKE2
      immunization were cross-reactive to hypervariable region-1 peptides from
      different genotypes. Immunization with the pIDKE2 also generated a positive
      cellular immune response against the core antigen, determined by interferon-gamma
      enzyme-linked immunospot (ELISPOT) assay, and induced detectable levels of
      interferon-gamma but not interleukin-4 in vaccinated mice. The detection of both
      antibody and cytotoxic T-lymphocyte responses, potentially targeted to
      circulating or cell-infecting virions respectively, in mice vaccinated with the
      pIDKE2 plasmid is very attractive for the effective eradication of HCV infection.

PMID- 12074701
TI  - Colonization of neonatal puppies by Staphylococcus intermedius.
AB  - Cutaneous and mucosal carriage of Staphylococcus intermedius was determined in
      five Cavalier King Charles spaniel bitches, living in normal domestic
      environment, and their 18 puppies during the immediate prepartum period and after
      whelping, over a total of 8 weeks, using quantitative swab techniques. Within 8 h
      of birth S. intermedius was isolated from each puppy. The nose and mouth were the
      most frequently colonized mucosal sites (83 and 78%, respectively). At that time
      S. intermedius was isolated from the abdominal skin in 78% of the puppies. One
      day postpartum the mucosal populations increased significantly (P < 0.001) but
      fell 6 (P < 0.01) and 20 (P < 0.001) days later. Populations from abdominal skin
      reduced during the first and fourth weeks postpartum (P < 0.05 for both). This
      study indicates that in the domestic environment S. intermedius establishes
      itself soon after birth. The level of colonization by S. intermedius in the
      bitches seems to influence the colonization by pathogenic staphylococci in
      puppies.

PMID- 12074702
TI  - The effects of capsaicin topical therapy in dogs with atopic dermatitis: a
      randomized, double-blinded, placebo-controlled, cross-over clinical trial.
AB  - The efficacy of twice daily topical application of capsaicin (0.025%) for the
      management of pruritus in dogs with atopic dermatitis (AD) was evaluated in
      double-blinded, placebo-controlled study. Twelve dogs with AD were randomly
      assigned to either 0.025% capsaicin or vehicle lotion applied twice daily for 6
      weeks. After a 4-week wash-out period, treatments were switched. Significant
      improvement was reported by owners (P = 0.0006), but not by investigators. Owners
      noted temporary worsening of pruritus after the first week of capsaicin therapy.
      Overall capsaicin was well tolerated. Substance P (SP) concentrations in the skin
      did not correlate with the severity of the pruritus and did not change
      significantly over time and between treatments. Lesional skin had less SP than
      nonlesional skin (P = 0.03). These observations suggest that topical capsaicin
      should be further evaluated as an adjunctive antipruritic agent in dogs with AD.

PMID- 12074704
TI  - A semiquantitative cytological evaluation of normal and pathological samples from
      the external ear canal of dogs and cats.
AB  - Numbers of desquamated epithelial cells, yeast cells and bacterial organisms were
      counted in samples collected from the external ear canal of 37 normal dogs and 16
      normal cats, and from 24 dogs and 22 cats with otitis externa. The aims of the
      study were to establish quantitative reference ranges and to correlate these data
      with the clinical status of the dogs and cats. Numbers of yeast cells and
      bacterial organisms were significantly increased in dogs (P = 0.05; P = 0.0001)
      and cats (P = 0.0001; P = 0.0001) with otitis externa, and in most cases high
      counts were correlated with clinical signs. Mean Malassezia counts per high-power
      dry field of > or = 5 in the dog and > or = 12 in the cat were considered
      abnormal. Mean bacterial counts per high-power dry field of > or = 25 in the dog
      and > or = 15 in the cat were considered abnormal. When used to differentiate
      normal from inflamed external ear canals, these figures provided a low
      sensitivity but a specificity of > or = 95%.

PMID- 12074703
TI  - Identification of major allergens of Malassezia pachydermatis in dogs with atopic
      dermatitis and Malassezia overgrowth.
AB  - We have previously shown that both atopic and normal dogs generate an IgG
      response to antigens of Malassezia pachydermatis. The aim of this study was to
      compare IgE responses to separated proteins of M. pachydermatis in 28 atopic dogs
      with Malassezia dermatitis and 22 clinically normal dogs using Western
      immunoblotting. Six different detection systems were evaluated in order to assess
      sensitivity and eliminate nonspecific binding and cross-reactivity. The protocol
      yielding the best results utilized a monoclonal mouse antidog IgE, an alkaline
      phosphatase conjugated goat antimouse IgG which had been passed through a canine
      IgG column 3 times, a chemiluminescent substrate and a digital imaging system.
      Proteins of 45, 52, 56 and 63 kDa were recognized by more than 50% of the atopic
      dog sera and thus represented major allergens. Only a minority of normal dogs
      showed faint IgE binding to these proteins. The results indicate that the
      majority of atopic dogs with Malassezia dermatitis have a greater IgE response
      than normal dogs, suggesting an IgE-mediated immune response may be clinically
      important in the pathogenesis of the disease.

PMID- 12074705
TI  - Effects of in utero retinoic acid exposure on mouse pelage hair follicle
      development.
AB  - We investigated in vivo the histological and immunohistochemical responses of
      mouse hair pelage follicle morphogenesis to prenatal exposure to a potentially
      nonteratogenic dose of all-trans-retinoic acid (RA), as a basis studying the
      preventive effect of RA on adult mouse skin carcinogenesis. In pregnant mice, a
      single oral dose of RA at 30 mg kg-1 body weight given on day 11.5 of gestation
      caused no RA-induced changes in the morphology or temporal expression patterns of
      keratins during pelage hair follicle morphogenesis. The only differential effect
      of RA was a statistically significant increase in the number of BrdU-positive
      nuclei in hair bulbs from RA exposed fetuses compared with nonexposed mice. The
      absence of adverse RA effects suggests that this experimental design may
      represent a valuable protocol for use in studies on the in vivo effects of this
      retinoid on different skin diseases.

PMID- 12074706
TI  - Characterization of a monoclonal antibody against desmoplakin 1 for use in dogs.
AB  - Skin biopsy specimens from face, axilla, abdomen and thigh, mucocutaneous tissues
      from anus and vagina, and oral mucosa from six healthy Beagle dogs were examined
      for desmoplakin (Dsp) immunoreactivity using immunoblotting and
      immunohistochemical analysis. With immunoblotting using mouse antihuman Dsp 1
      monoclonal antibody (DP2.17), a band was detected at 250 kDa in all the extracts
      as in normal human skin samples, although no band was detected at 210 kDa,
      suggesting that monoclonal antibody DP2.17 recognizes canine Dsp 1 but not Dsp 2.
      Moreover, the desmosome regions of all specimens were stained with DP2.17 using
      immunohistochemical analysis. From these results, DP2.17, developed for the
      examination of human skin, might be suitable for the investigation of Dsp-related
      skin disorders in dogs.

PMID- 12074707
TI  - CTL: Caspases Terminate Life, but that's not the whole story.
AB  - The induction of cell death by cytotoxic T-lymphocytes (CTL) or natural killer
      (NK) cells is one of the main ways by which higher organisms protect themselves
      from rogue cells, including those infected by a virus, or posing a risk of
      cancer. Considering the rapidity of viral replication and spread to uninfected
      cells, CTL and NK are extremely efficient killers. This is at least partly due to
      the variety of pathways that these cytolytic lymphocytes (CL) can use to ensure
      the death of a cell. Primarily, CL utilize two independently initiated pathways
      involving either ligation of death receptors or perforin mediated trafficking of
      granzyme B to the target cell cytosol to activate a family of death proteases
      (caspases) in the target cell. The caspases then orchestrate the orderly
      dismantling of that cell by cleavage of a set of critical substrates. If caspases
      are inactivated, due either to mutations in proteins that signal their activation
      or direct inhibition by a viral gene product, CL can utilize a caspase
      independent pathway to ensure the death of the target cell. Here we will discuss
      the mechanisms by which these stellar killers achieve their goal.

PMID- 12074708
TI  - Genotyping of human killer-cell immunoglobulin-like receptor genes by polymerase
      chain reaction with sequence-specific primers: an update.
AB  - Killer-cell Immunoglobulin-like Receptors (KIR) help human natural killer (NK)
      cells counteract infections by pathogens that evade the immune system by inducing
      down-regulation of HLA class I molecules in infected cells. KIRs are structural
      and functionally diverse receptors encoded by a family of polymorphic genes. The
      most extreme aspect of KIR polymorphism is the varying content of KIR-genes in
      the genome of different individuals, as first demonstrated by KIR genotyping
      using the PCR-SSP method. Knowledge on the KIR-gene family has been recently
      expanded by the identification of new genes, pseudogenes and multiple gene
      variants, several of which escaped detection by the original genotyping
      technique. We present here an upgraded PCR-SSP method for KIR genotyping that
      integrates recent achievements in the research of the diversity of this gene
      family. Our method permits detection of all known KIR genes and pseudogenes in a
      16-reaction set. Furthermore, an additional set of six reactions permits
      subtyping of KIR2DL5 variants, each of which shows well-differentiated functional
      and genetic features.

PMID- 12074709
TI  - Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles
      and haplotypes in dogs.
AB  - The DLA class II genes in the dog major histocompatibility complex are highly
      polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences
      have been assigned. The aim of this study was to examine the intrabreed and
      interbreed variation of DLA allele and haplotype frequencies in dogs, and to
      ascertain whether conserved DLA class II haplotypes occur within and between
      different breeds. One thousand and 25 DNA samples from over 80 different breeds
      were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61.
      DNA sequence based typing and sequence specific oligonucleotide probing were used
      to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high
      frequency of DLA class II homozygous animals (35%), allowed the assignment of
      many haplotypes despite the absence of family data. Four new DLA alleles were
      identified during the course of this study. Analysis of the data revealed
      considerable interbreed variation, not only in allele frequency, but also in the
      numbers of alleles found per breed. There was also considerable variation in the
      number of breeds in which particular alleles were found. These interbreed
      variations were found in all three DLA class II loci tested, and also applied to
      the three-locus haplotypes identified. Within this data set, 58 different DLA
      DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at
      least two different animals. Some of the haplotypes appeared to be characteristic
      of certain breeds. The high interbreed, and relatively low intrabreed, variation
      of MHC alleles and haplotypes found in this study could provide an explanation
      for reports of interbreed variation of immune responses to vaccines, viruses and
      other infections.

PMID- 12074710
TI  - Cellular, serological, and molecular polymorphism of the class I and class II
      loci of the canine Major Histocompatibility Complex.
AB  - This study was undertaken to determine the relationships between canine cellular
      and serological determinants and more recently described genes. Such
      relationships might reveal information about immunological reactivity or function
      of various proteins. To do this we studied the haplotypic associations of dog
      leukocyte antigen (DLA) class I and class II alleles determined from a panel of
      14 DLA-D homozygous dogs. This panel of dogs was typed for the serological
      determinants DLA-A, DLA-B and DLA-C. Polymorphisms for DLA-DQA1, DLA-DQB1, DLA
      DRB1 and DLA-88 were also determined. The number of alleles (one or two) for two
      microsatellite markers in the DLA region were also determined. Analyses of the
      nucleotide sequences and of the serological and cellular typing data revealed
      that phenotypic homozygosity, as defined by the DLA-D type in mixed leukocyte
      culture (MLC), tended to correlate with homozygosity at the DLA-DRB1 locus but
      not necessarily at the DLA-DQB1 locus. Furthermore, MLC specificity was
      determined by other loci besides DLA-DRB1 and DLA-DQB1. The amino acid at
      position 63 of the DR beta chain could contribute to the DLA-B serological
      specificity. DLA-88, the most polymorphic class I gene characterized to date, did
      not have an easily identifiable association with either the DLA-A or DLA-C class
      I serological specificities. Homozygosity or heterozygosity of each of two
      microsatellite markers, FH 2200 and FH 2202, located in the class I or class II
      region, respectively, did not correlate with homozygosity or heterozygosity of
      the most polymorphic known class I (DLA-88) or class II (DLA-DRB1) genes.

PMID- 12074711
TI  - HLA Class I typing of volunteers for a bone marrow registry: QC analysis by DNA
      based methodology identifies serological typing discrepancies in the assignment
      of HLA-A and B antigens.
AB  - Until recently, the majority of newly recruited volunteer donors were typed for
      HLA-A and -B by serology onto the National Marrow Donor Program Registry. Quality
      control of this serological typing performed by contracted laboratories was
      carried out by retesting approximately 1% of each laboratory's test volume
      utilizing DNA-based techniques (SSOP). The criteria used for selection included
      samples presumed to be homozygotes, samples with split antigen specificities and
      samples with antigens considered to be difficult to define. Out of 1983 samples
      analyzed, 156 HLA-A (3.9%) and 265 HLA-B (6.7%) locus discrepancies were
      identified. Review of these discrepancies by both the serological and QC
      laboratory revealed that the majority of discrepancies were due to errors in
      serological typing. Serological discrepancies were categorized as follows: blank
      antigens identified (36.8%) and misassignments (63.2%). Misassignments were
      defined as either the incorrect assignment of antigens within a group ("wrong
      split"), or a complete misassignment. Antigens reported as blanks most frequently
      belonged to the A19 and A28 groups and to the B70, 46 and 40 groups. The most
      frequent misassignments within groups were the A19 and A10 groups, and the B40
      and B15 groups. Other HLA-A misassignments included A2 vs A28 or A2 vs A69, while
      other HLA-B misassignments included B35 and B70. This QC analysis showed that
      serological typing of class I antigens for the purposes of NMDP registry typing
      is prone to a significant error rate. Careful evaluation and selection of
      contracted laboratories by the NMDP suggests methodological limitations rather
      than poor performance as the main cause of these observations.

PMID- 12074712
TI  - Identification of a new MICA allele, MICA*047.
AB  - The MHC Class I related (MIC) gene family has been shown to be very polymorphic
      with 46 different MICA alleles being officially named by the WHO Nomenclature
      Committee for factors of the HLA system to date. We have identified a novel MICA
      allele, MICA*047, in a Coya American Indian individual from the Jujuy province of
      north-western Argentina. The novel MICA*047 allele differs from the MICA*030
      allele by a single non-synonymous substitution in exon 2, condon 26 GTA-->GGA,
      Valine to Glycine1.

PMID- 12074713
TI  - Triplet repeat polymorphism in the transmembrane region of the MICA gene in
      celiac disease.
AB  - Celiac disease (CD) is characterized by a striking expansion of gamma delta T
      cells in the intestine. These cells interact with MICA, a cell surface protein
      encoded by a major histocompatibility complex gene. We investigated whether MICA
      gene polymorphism could contribute to susceptibility to CD. DNA typing for HLA
      DR, DQA1, DQB1, TNF-308, TNFa, TNFb and a triplet repeat polymorphism in the
      transmembrane region of the MICA gene were carried out. We performed case-control
      stratified association studies and transmission disequilibrium tests. Our results
      indicate that although there is no primary association between MICA polymorphism
      and CD, there is, in addition to HLA-DQ, a second susceptibility locus on the 8.1
      ancestral haplotype in strong linkage disequilibrium with MICA A5.1 allele.

PMID- 12074714
TI  - Distribution of HLA-B alleles in nasopharyngeal carcinoma patients and normal
      controls in Thailand.
AB  - HLA-B frequencies in 54 unrelated nasopharyngeal carcinoma (NPC) patients and 49
      healthy random controls in Thailand were investigated by direct DNA sequencing.
      Similar to previous reports in Chinese NPC patients, HLA-B*4601 was observed at a
      greater frequency in patients (21/54 (40%)) compared to controls (7/49 (14%). An
      increase in HLA-B*51012 was also demonstrated. B*51012 was present in 6/54 (11%)
      NPC patients but was not observed (0%) in controls. B*44032 was associated with a
      decreased risk. Five out of 54 (9%) NPC patients had B*44032 compared to 14/49
      (29%) in the control group.

PMID- 12074716
TI  - Seven new HLA-B alleles associated with antigens in the B7 CREG.
AB  - This paper describes seven novel HLA-B alleles. Five of these new alleles contain
      polymorphic motifs previously reported in HLA-B alleles, suggesting an origin
      resultant from a gene conversion mechanism. B*0723 contains a polymorphism
      previously unreported in class I HLA molecules. B*4105 contains a nucleotide
      substitution previously unreported in class I HLA molecules, which encodes a
      protein sequence previously reported only in HLA-C locus alleles.

PMID- 12074715
TI  - Two new HLA Cw* alleles, Cw*0105 and Cw*1405, detected by sequence based typing.
AB  - During recent years, the view of the relative importance of the HLA Cw locus has
      undergone substantial change. From being an HLA locus with both limited
      polymorphism and biological significance there are now more than a hundred
      different alleles known and the biological importance of HLA Cw, both as a
      transplantation antigen and as a receptor for NK cells, is well established.
      Sequence based typing has been shown to be a powerful tool, especially for HLA Cw
      typing. Here we describe two new HLA Cw* alleles found during routine typing of
      potential bone marrow donors and hematological patients. The HLA Cw*0105 differs
      from Cw*0102 at positions 361 and 368 in exon 3 leading to a Trp to Arg and Cys
      to Ser substitution, respectively. HLA Cw*1405 differs from Cw*14021 by a single
      nucleotide substitution at position 368. This mutation results in an amino acid
      substitution of Phe for Tyr.

PMID- 12074717
TI  - Novel HLA-DRB3 alleles discovered during routine sequencing based typing,
      DRB3*02023, DRB3*0212, DRB3*0213 and DRB3*03012.
AB  - We report the discovery of four HLA-DRB3 alleles during routine sequencing based
      typing (SBT); DRB3*02023, DRB3*0212, DRB3*0213 and DRB3*03012. These alleles
      differ from other HLA-DRB3 alleles by previously undescribed single nucleotide
      polymorphisms.

PMID- 12074718
TI  - Nomenclature for factors of the HLA system, update January 2002.

PMID- 12074719
TI  - Nomenclature for factors of the HLA system, update February 2002.

PMID- 12074720
TI  - Nomenclature for factors of the HLA system, update March 2002.

PMID- 12074721
TI  - Community genetics in the Northwestern Atlantic intertidal.
AB  - Our ability to make inferences about the processes acting upon a biological
      system can be dramatically improved through integration of information from other
      fields. In particular, this is true of the field of phylogeography, a discipline
      that attempts to describe geographical variation in species using neutral genetic
      diversity as a correlate of time. Through comparisons of information from
      multiple species, as well as background information about the abiotic environment
      and how it has changed over time, we should be able to reassemble many of the
      forces that were important in assembling the communities and community
      interactions found in a given region. Here I review the information available for
      coastal species in the northwestern Atlantic, and argue that an integration of
      ecological, genetic, geological and oceanographic information can illustrate
      emergent patterns of community genetics.

PMID- 12074722
TI  - Sampling within the genome for measuring within-population diversity: trade-offs
      between markers.
AB  - Experimental results of diversity estimates in a set of populations often exhibit
      contradictory patterns when different marker systems are used. Using simulations
      we identified potential causes for these discrepancies. These investigations
      aimed also to detect whether different sampling strategies of markers within the
      genome resulted in different estimates of the diversity at the whole genome
      level. The simulations consisted in generating a set of populations undergoing
      various evolutionary scenarios which differed by population size, migration rate
      and heterogeneity of gene flow. Population diversity was then computed for the
      whole genome and for subsets of loci corresponding to different marker
      techniques. Rank correlation between the two measures of diversity were
      investigated under different scenarios. We showed that the heterogeneity of
      genetic diversity either between loci (genomic heterogeneity, GH) or among
      populations (population heterogeneity, PH) varied greatly according to the
      evolutionary scenario considered. Furthermore, GH and PH were major determinants
      of the level of rank correlation between estimates of genetic diversities
      obtained using different kinds of markers. We found a strong positive
      relationship between the level of the correlation and PH, whatever the marker
      system. It was also shown that, when GH values were constantly low during
      generations, a reduced number of microsatellites was enough to predict the
      diversity of the whole genome, whereas when GH increased, more loci were needed
      to predict the diversity and amplified fragment length polymorphism markers would
      be more recommended in this case. Finally the results are discussed to recommend
      strategies for gene diversity surveys.

PMID- 12074723
TI  - A Bayesian approach to inferring population structure from dominant markers.
AB  - Molecular markers derived from polymerase chain reaction (PCR) amplification of
      genomic DNA are an important part of the toolkit of evolutionary geneticists.
      Random amplified polymorphic DNA markers (RAPDs), amplified fragment length
      polymorphisms (AFLPs) and intersimple sequence repeat (ISSR) polymorphisms allow
      analysis of species for which previous DNA sequence information is lacking, but
      dominance makes it impossible to apply standard techniques to calculate F
      statistics. We describe a Bayesian method that allows direct estimates of FST
      from dominant markers. In contrast to existing alternatives, we do not assume
      previous knowledge of the degree of within-population inbreeding. In particular,
      we do not assume that genotypes within populations are in Hardy-Weinberg
      proportions. Our estimate of FST incorporates uncertainty about the magnitude of
      within-population inbreeding. Simulations show that samples from even a
      relatively small number of loci and populations produce reliable estimates of
      FST. Moreover, some information about the degree of within-population inbreeding
      (FIS) is available from data sets with a large number of loci and populations. We
      illustrate the method with a reanalysis of RAPD data from 14 populations of a
      North American orchid, Platanthera leucophaea.

PMID- 12074724
TI  - Population structure of plaice (Pleuronectes platessa L.) in northern Europe:
      microsatellites revealed large-scale spatial and temporal homogeneity.
AB  - Philopatry to spawning grounds combined with well-known migratory patterns in the
      flatfish Pleuronectes platessa (plaice) has led to the hypothesis that regional
      populations may reflect relatively discrete, genetic stocks. Using six
      microsatellite loci we genotyped 240 adult individuals collected from locations
      in Norway, the Faeroe plateau, the Irish Sea, the Femer Baelt, Denmark, and the
      southern North Sea, and 240 0-class juveniles collected from five nursery-ground
      locations in Iceland, northwest Scotland, two sites in the Wadden Sea, and the
      Bay of Vilaine in Southern Brittany. The mean number of alleles/locus ranged from
      5.3 to 20.4, with a mean of 13.9. Expected heterozygosity was uniformly high
      across all locations (multilocus H(exp)= 0.744 +/- 0.02). Pairwise comparisons of
      theta; among all 11 locations revealed significant differentiation between
      Iceland and all other locations (theta = 0.0290*** to 0.0456***), which is
      consistent with the deep-water barrier to dispersal in plaice. In contrast, no
      significant differentiation was found among any of the remaining continental
      shelf sampling locations. This suggests that regional stocks are themselves
      composed of several genetic stocks under a model of panmixia which persists even
      to the spawning grounds. The presence of significant heterozygote deficiencies at
      all locations (not due to null alleles) suggests a temporal Wahlund effect yet
      the absence of significant population differentiation among continental shelf
      localities makes this explanation alone, difficult to reconcile. Sampling of eggs
      at the spawning grounds will be required to resolve this issue. Causes of the
      mismatch between genetic and geographical stocks is discussed in the context of
      high gene flow.

PMID- 12074725
TI  - The phylogeography and connectivity of the latitudinally widespread scleractinian
      coral Plesiastrea versipora in the Western Pacific.
AB  - Whereas terrestrial animal populations might show genetic connectivity within a
      continent, marine species, such as hermatypic corals, may have connectivity
      stretching to all corners of the planet. We quantified the genetic variability
      within and among populations of the widespread scleractinian coral, Plesiastrea
      versipora along the eastern Australian seaboard (4145 km) and the Ryukyu
      Archipelago (Japan, 681 km) using sequences of internal transcribed spacers (ITS1
      2) from ribosomal DNA. Geographic patterns in genetic variability were deduced
      from a nested clade analysis (NCA) performed on a parsimony network haplotype.
      This analysis allowed the establishment of geographical associations in the
      distribution of haplotypes within the network cladogram, therefore allowing us to
      deduce phylogeographical patterns based under models of restricted gene flow,
      fragmentation and range expansion. No significant structure was found among
      Ryukyu Archipelago populations. The lack of an association between the positions
      of haplotypes in the cladogram with geographical location of these populations
      may be accounted for by a high level of gene flow of P. versipora within this
      region, probably due to the strong Kuroshio Current. In contrast, strong
      geographical associations were apparent among populations of P. versipora along
      the south-east coast of Australia. This pattern of restricted genetic
      connectivity among populations of P. versipora on the eastern seaboard of
      Australia seems to be associated with the present surface ocean current (the East
      Australian Current) on this side of the south-western Pacific Ocean.

PMID- 12074726
TI  - Reproductive mode and genetic variation suggest a North American origin of
      European Letharia vulpina.
AB  - Our data on the intercontinental population biology of Letharia vulpina show an
      unexpected shift from a recombining North American population with unique
      haplotypes to genetically depauperate Swedish and Italian populations, each with
      many representatives of a single repeated haplotype. Analysis of eight loci in 47
      individuals supported recombination in North American populations and showed
      almost no variation among European populations. We infer that a genetic
      bottleneck caused by limited long-distance dispersal accounts for the lack of
      genetic variation found in marginal populations. This lack of variation in the
      European populations makes it impossible to use population genetic means to
      distinguish clonal reproduction from self-fertilization or even outcrossing, but
      phenotype indicates that reproduction in the marginal populations is by clonal
      spread, via soredia and isidioid soredia.

PMID- 12074727
TI  - An exceptional case of historical outbreeding in African sable antelope
      populations.
AB  - Empirical investigations of intraspecific outbreeding and subsequent
      introgressive hybridization in natural populations are rare, particularly among
      conspecific populations of large mammals. Using mitochondrial DNA data [partial
      control region (496 basepairs - bp) and cytochrome b gene (343 bp) sequences
      analysed from 95 individuals representing 17 sampling locations scattered through
      the African miombo (Brachystegia) woodland ecosystem] and phylogeographical
      statistical procedures (gene genealogy, nested cladistic and admixture proportion
      analyses), we (i) give a detailed dissection of the geographical genetic
      structure of Hippotragus niger; (ii) infer the processes and events potentially
      involved in the population history; and (iii) trace extensive introgressive
      hybridization in the species. The present-day sable antelope population shows a
      tripartite pattern of genetic subdivision representing West Tanzanian, Kenya/East
      Tanzanian and Southern Africa locations. Nested clade analysis revealed that past
      allopatric fragmentation, caused probably by habitat discontinuities associated
      with the East African Rift Valley system, together with intermediary episodic
      long-distance colonization and restricted, recurrent gene flow have played an
      predominant role in shaping the extent of maternal genetic diversity (10.4%) and
      population structure. An extensive (average rate of admixture = 20.0%), but
      geographically circumscribed and unidirectional hybridization event in the past
      was inferred, resulting in an extreme (the highest discovered so far in mammals)
      intraspecific difference of 18.2% among morphologically monotypic sable antelopes
      from West Tanzania. The results are used to provide an evolutionary framework
      within which taxonomic implications and conservation decisions can be evaluated.

PMID- 12074728
TI  - New insights into the distribution of polyploid Daphnia: the Holarctic revisited
      and Argentina explored.
AB  - It has long been known that polyploid organisms are more prevalent in arctic than
      in temperate environments. Past explanations for this geographical trend have
      focused on the role of glacial cycles in generating polyploids and the influence
      of abiotic factors in favouring polyploidy in the north. In combination, these
      mechanisms probably suffice to explain the observed geographical cline in ploidy
      levels in members of the Daphnia pulex complex in the Holarctic. While only
      diploid members of the D. pulex complex are found in the temperate regions of
      North America and Europe, allozyme and DNA quantification analyses indicate that
      the southern Argentine pulex-complex fauna is dominated by polyploids. Indeed,
      the present study is the first to document the presence of polyploid members of
      the D. pulex complex in any temperate climate. The results of phylogeographic
      analyses suggest that this difference in polyploid distribution between the
      northern and southern hemispheres is based more on ecological and historical
      contingencies than direct selection for polyploidy. Specifically, competition
      with diploid relatives probably limits the lower latitudinal range of polyploids
      in the north, but appears not to have occurred in Argentina. Because of these
      differences, the present study provides important insights into the diverse
      factors that determine the distributions and evolutionary fates of polyploid
      organisms.

PMID- 12074729
TI  - A distinct Bemisia tabaci (Gennadius) (Hemiptera: Sternorrhyncha: Aleyrodidae)
      genotype cluster is associated with the epidemic of severe cassava mosaic virus
      disease in Uganda.
AB  - During the 1990s, an epidemic of cassava mosaic virus disease caused major losses
      to cassava production in Uganda. Two factors associated with the epidemic were
      the occurrence of a novel recombinant begomovirus, EACMV-Ug, and unusually high
      populations of the whitefly vector, Bemisia tabaci. Here we present molecular
      evidence for the occurrence of two cassava-colonizing B. tabaci genotype
      clusters, Ug1 and Ug2, one of which, Ug2, can be consistently associated with the
      CMD epidemic in Uganda at the time of collection in 1997. By contrast, a second
      genotype cluster, Ug1, only occurred 'at' or 'ahead of' the epidemic 'front',
      sometimes in mixtures with Ug2. Comparison of mitochondrial cytochrome oxidase I
      gene sequences for Ug1 and Ug2 and well-studied B. tabaci reference populations
      indicated that the two Ugandan populations exhibited approximately 8% divergence,
      suggesting they represent distinct sub-Saharan African lineages. Neither Ugandan
      genotype cluster was identified as the widely distributed, polyphagous, and
      highly fecund B biotype of Old World origin, with which they both diverged by
      approximately 8%. Within genotype cluster divergence of Ug1 at 0.61 +/- 0.1% was
      twice that of Ug2 at 0.35 +/- 0.1%. Mismatch analysis suggested that Ug2 has
      undergone a recent population expansion and may be of nonUgandan origin, whereas
      Ug1 has diverged more slowly, and is likely to be an indigenous genotype cluster.

PMID- 12074730
TI  - Sex-specific genetic structure in Schistosoma mansoni: evolutionary and
      epidemiological implications.
AB  - We studied the population genetic structure of 360 and 1247 adult Schistosoma
      mansoni using seven microsatellite and seven random amplified polymorphic DNA
      (RAPD) markers, respectively. Parasites were collected from their natural
      definitive host Rattus rattus in Guadeloupe (West Indies). We found a sex
      specific genetic structure, a pattern never before reported in a parasitic
      organism. Male genotypes were more randomly distributed among rats than female
      genotypes. This interpretation was consistent with a lower differentiation
      between hosts for males relative to females, the higher genetic similarity
      between females in the same host and the observed local (i.e. within-individual
      host) differences in allele frequencies between the two sexes. We discuss our
      results using ecological and immunological perspectives on host-parasite
      relationships. These results change our view on the epidemiology of
      schistosomiasis, a serious disease affecting humans in African and American
      intertropical zones.

PMID- 12074731
TI  - Reproductive success in reindeer males in a herd with varying sex ratio.
AB  - In polygynous species, male reproductive success is often correlated with
      dominance status of individual males and sex ratio in the population. Reindeer,
      Rangifer tarandus, is a polygynous species, and here we compared the variation in
      male reproductive success and dominance status during two successive years in a
      herd with a male:female sex ratio of 1:7 and 1:3. Copulations were recorded,
      together with data on male dominance hierarchy and size of mating groups. Male
      reproductive success was estimated by paternity analysis of calves using
      microsatellite DNA markers. The distribution of reproductive success among the
      males was highly skewed for both years with the most dominant male also being the
      most successful. The largest mating group was established in the herd with the
      least skew in sex ratio. In this herd some of the adult males present were less
      reproductively successful than some of the more subordinate younger males.
      Estimates of the mating group size of males, correcting for dominance status when
      more than one male is present in the groups, gave good prediction of individual
      males' reproductive success.